PMID- 22948020
TI  - Cell cycle: clathrin helps centrosomes come of age.

PMID- 22948021
TI  - Polymorphisms and expression of TLR4 and 9 in malaria in two ethnic groups of
      Assam, northeast India.
AB  - Infectious diseases have been postulated to play an important role in exerting
      pressure and in selection of TLR polymorphisms. Single nucelotide polymorphisms
      (SNPs) of TLR4 have been reported to show unique distributions in populations
      from Africa, Asia and Europe, and malaria is suggested to influence these
      patterns. In this context, we examined association of TLR polymorphisms with the
      risk of malaria in two ethnic groups-the Austro-Asiatics and Tibeto-Burmans-from
      malaria endemic districts of Assam to understand the influence of malaria in
      selection of TLRs in these genetically-distinct populations. TLR9 (T-1237C)
      mutation was positively associated with complicated (P = 0.001) and frequent (P =
      0.035) malaria in Austro-Asiatics (relative risk = 0.595 95% CI: 0.479-0.836),
      but not in Tibeto-Burmans. Nonetheless, these alleles were not in Hardy-Weinberg
      Equilibrium in Tibeto-Burmans (P < 0.001). In contrast, the TLR9 1486T/C genotype
      was favourable where it was negatively associated with complicated malaria
      (Fishers exact P = 0.014). Sequencing data revealed that the two populations
      differed in nucleotide diversity of the TLR9 promoter region. Enhanced expression
      of TLR4 (P = 0.05), but not of TLR9, was associated with complicated malaria.
      Austro-Asiatics appeared to have accumulated favourable genotypes of TLR9,
      perhaps because of their longer exposure to malaria.

PMID- 22948022
TI  - Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset
      analysis.
AB  - Prostate cancer (PrCa) is the most common male cancer in developed countries and
      the second most common cause of cancer death after lung cancer. We recently
      reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families,
      which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The
      aim of this study was to identify and to detect other loci linked to HPC. Here we
      used ordered subset analysis (OSA), conditioned on nonparametric linkage to these
      loci to detect other loci linked to HPC in subsets of families, but not the
      overall sample. We analyzed the families based on their evidence for linkage to
      chromosome 2, chromosome 17 and a maximum score using the strongest evidence of
      linkage from either of the two loci. Significant linkage to a 5-cM linkage
      interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on
      Xq26.3-q27 (DeltaLOD=3.193, empirical P=0.009) was observed in a subset of 41
      families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were
      novel to the analysis combining linkage evidence from both primary loci were
      identified; 18q12.1-q12.2 (OSA LOD=2.541, DeltaLOD=1.651, P=0.03) and 22q11.1
      q11.21 (OSA LOD=2.395, DeltaLOD=2.36, P=0.006), which is close to HPC6. Using OSA
      allows us to find additional loci linked to HPC in subsets of families, and
      underlines the complex genetic heterogeneity of HPC even in highly aggregated
      families.

PMID- 22948023
TI  - Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria.
AB  - De novo mutations in the TUBA1A gene are responsible for a wide spectrum of
      neuronal migration disorders, ranging from lissencephaly to perisylvian
      pachygyria. Recently, one family with polymicrogyria (PMG) and mutation in TUBA1A
      was reported. Hence, the purpose of our study was to determine the frequency of
      TUBA1A mutations in patients with PMG and better define clinical and imaging
      characteristics for TUBA1A-related PMG. We collected 95 sporadic patients with
      non-syndromic bilateral PMG, including 54 with perisylvian PMG and 30 PMG with
      additional brain abnormalities. Mutation analysis of the TUBA1A gene was
      performed by sequencing of PCR fragments corresponding to TUBA1A-coding
      sequences. Three de novo missense TUBA1A mutations were identified in three
      unrelated patients with PMG representing 3.1% of PMG and 10% of PMGs with complex
      cerebral malformations. These patients had bilateral perisylvian asymmetrical PMG
      with dysmorphic basal ganglia cerebellar vermian dysplasia and pontine
      hypoplasia. These mutations (p.Tyr161His; p.Val235Leu; p.Arg390Cys) appear
      distributed throughout the primary structure of the alpha-tubulin polypeptide,
      but their localization within the tertiary structure suggests that PMG-related
      mutations are likely to impact microtubule dynamics, stability and/or local
      interactions with partner proteins. These findings broaden the phenotypic
      spectrum associated with TUBA1A mutations to PMG and further emphasize that
      additional brain abnormalities, that is, dysmorphic basal ganglia, hypoplastic
      pons and cerebellar dysplasia are key features for the diagnosis of TUBA1A
      related PMG.

PMID- 22948024
TI  - Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome.
AB  - Lynch syndrome (LS) is an inherited cancer-predisposing disorder caused by
      germline mutations in the mismatch repair (MMR) genes. The high variability in
      individual cancer risk observed among LS patients suggests the existence of
      modifying factors. Identifying genetic modifiers of risk could help implement
      personalized surveillance programs based on predicted cancer risks. Here we
      evaluate the role of the telomerase (hTERT) rs2075786 SNP as a cancer-risk
      modifier in LS, studying 255 and 675 MMR gene mutation carriers from Spain and
      the Netherlands, respectively. The study of the Spanish sample revealed that the
      minor allele (A) confers increased cancer risk at an early age. The analysis of
      the Dutch sample confirmed the association of the A allele, especially in
      homozygosity, with increased cancer risk in mutation carriers under the age of 45
      (relative riskLSca<45_AA=2.90; 95% confidence interval=1.02-8.26). Rs2075786 is
      associated with colorectal cancer (CRC) risk neither in the general population
      nor in non-Lynch CRC families. In silico studies predicted that the SNP causes
      the disruption of a transcription binding site for a retinoid receptor, retinoid
      X receptor alpha, probably causing early telomerase activation and therefore
      accelerated carcinogenesis. Notably, cancer-affected LS patients with the AA
      genotype have shorter telomeres than those with GG. In conclusion, MMR gene
      mutation carriers with hTERT rs2075786 are at high risk to develop a LS-related
      tumor at an early age. Cancer-preventive measures and stricter cancer
      surveillance at early ages might help prevent or early detect cancer in these
      mutation carriers.

PMID- 22948025
TI  - Molecular alterations and expression of succinate dehydrogenase complex in wild
      type KIT/PDGFRA/BRAF gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract, disclosing somatic KIT, PDGFRA and BRAF mutations.
      Loss of function of succinate dehydrogenase (SDH) complex is an alternative
      molecular mechanism in GISTs, namely in carriers of germline mutations of the SDH
      complex that develop Carney-Stratakis dyad characterized by multifocal GISTs and
      multicentric paragangliomas (PGLs). We studied a series of 25 apparently sporadic
      primary wild-type (WT) KIT/PDGFRA/BRAF GISTs occurring in patients without
      personal or familial history of PGLs, re-evaluated clinicopathological features
      and analyzed molecular alterations and immunohistochemistry expression of SDH
      complex. As control, we used a series of well characterized 49 KIT/PDGFRA/BRAF
      mutated GISTs. SDHB expression was absent in 20% and SDHB germline mutations were
      detected in 12% of WT GISTs. Germline SDHB mutations were significantly
      associated to younger age at diagnosis. A significant reduction in SDHB
      expression in WT GISTs was found when compared with KIT/PDGFRA/BRAF-mutated
      GISTs. No significant differences were found when comparing DOG-1 and c-KIT
      expression in WT, SDHB-mutated and KIT/PDGFRA/BRAF-mutated GISTs. Our results
      confirm the occurrence of germline SDH genes mutations in isolated, apparently
      sporadic WT GISTs. WT KIT/PDGFRA/BRAF GISTs without SDHB or SDHA/SDHB expression
      may correspond to Carney-Stratakis dyad or Carney triad. Most importantly, the
      possibility of PGLs (Carney-Stratakis dyad) and/or pulmonary chondroma (Carney
      triad) should be addressed in these patients and their kindred.

PMID- 22948026
TI  - High prevalence of occult paragangliomas in asymptomatic carriers of SDHD and
      SDHB gene mutations.
AB  - Hereditary paraganglioma is a benign tumor syndrome with an age-dependent
      penetrance. Carriers of germline mutations in the SDHB or SDHD genes may develop
      parasympathetic paragangliomas in the head and neck region or sympathetic
      catecholamine-secreting abdominal and thoracic paragangliomas
      (pheochromocytomas). In this study, we aimed to establish paraganglioma risk in
      101 asymptomatic germline mutation carriers and evaluate the results of our
      surveillance regimen. Asymptomatic carriers of an SDHD or SDHB mutation were
      included once disease status was established by MRI diagnosis. Clinical
      surveillance revealed a head and neck paraganglioma in 28 of the 47 (59.6%)
      asymptomatic SDHD mutation carriers. Risk of tumor development was significantly
      lower in SDHB mutation carriers: 2/17 (11.8%, P=0.001). Sympathetic
      paragangliomas were encountered in two SDHD mutation carriers and in one SDHB
      mutation carrier. In conclusion, asymptomatic carriers of an SDHD mutation are at
      a high risk for occult parasympathetic paraganglioma. SDHB carrier risk is
      considerably lower, consistent with lower penetrance of SDHB mutations. For both
      syndromes, the risk of symptomless sympathetic paragangliomas is small.

PMID- 22948027
TI  - Stronger signal of recent selection for lactase persistence in Maasai than in
      Europeans.
AB  - Continued ability to digest lactose after weaning provides a possible selective
      advantage to individuals who have access to milk as a food source. The lactase
      persistence (LP) phenotype exists at varying frequencies in different populations
      and SNPs that modulate the regulation of the LCT gene have been identified in
      many of these populations. Very strong positive selection for LP has been
      illustrated for a single SNP (rs4988235) in northwestern European populations,
      which has become a textbook example of the effect of recent selective sweeps on
      genetic variation and linkage disequilibrium. In this study, we employed two
      different methods to detect signatures of positive selection in an East African
      pastoralist population in the HapMap collection, the Maasai from Kenya, and
      compared results with other HapMap populations. We found that signatures of
      recent selection coinciding with the LCT gene are the strongest across the genome
      in the Maasai population. Furthermore, the genome-wide signal of recent positive
      selection on haplotypic variation and population differentiation around the LCT
      gene is greater in the Maasai than in the CEU population (northwestern European
      descent), possibly due to stronger selection pressure, but it could also be an
      indication of more recent selection in Maasai compared with the Central European
      group or more efficient selection in the Maasai due to less genetic drift for
      their larger effective population size. This signal of recent selection is driven
      by a putative East African LP haplotype that is different from the haplotype that
      contributes to the LP phenotype in northwestern Europe.

PMID- 22948028
TI  - Thymic stromal lymphopoietin: a promising therapeutic target for allergic
      diseases.
AB  - Thymic stromal lymphopoietin (TSLP), an interleukin 7-like cytokine, can trigger
      dendritic cell (DC)-mediated T-helper type 2 (Th2) inflammatory responses. Recent
      evidence demonstrates that cytokines TSLP and OX40 (CD134)/OX40 ligand seem to be
      important players in the maintenance of Th2 memory pool in the pathogenesis of
      asthma. Accumulating data reveal that the pathogenic T cells involved in asthma
      are likely to be inflammatory Th2 cells. TSLP is involved in the development of
      asthma through crosstalk with nuclear factor NF-KB. Progression of skin fibrosis
      in atopic dermatitis occurs via TSLP/TSLP receptor. TSLP-mediated dermal
      inflammation aggravates experimental allergic asthma. Also, TSLP polymorphisms
      are associated with susceptibility to asthma, atopic dermatitis, and eczema
      herpeticum. These findings suggest a master switch of TSLP in the initiation of
      allergic and adaptive inflammation through innate pathways at the epithelial cell
      DC interface. The TSLP pathway is therefore a promising target for immunotherapy
      of allergic diseases.

PMID- 22948029
TI  - Time-dependent transfer of 137Cs, 85Sr and 65Zn to earthworms in highly
      contaminated soils.
AB  - The transfer characteristics of (137)Cs, (85)Sr and (65)Zn to earthworms (Eisenia
      andrei) in soils with different amounts of the radionuclides have been
      investigated. The time-dependent whole-body concentration ratios (CR) were
      derived for worms in artificially contaminated soils with three different
      activity concentrations. Two parameters of a first order kinetic model, the
      equilibrium concentration ratio (CR(eq)) and the effective loss rate constant
      (k), were estimated by a comparison of experimental CR results with model
      predictions. The estimated CR(eq) (Bq/kg fresh worm per Bq/kg dry soil) ranged
      from 3.9 * 10(-4) to 4.1 * 10(-3) for (137)Cs, 1.39 * 10(-3) to 2.94 * 10(-2) for
      (85)Sr, and 1.39 * 10(-3) to 5.0 * 10(-2) for (65)Zn, and consistently decreased
      with increasing soil activity concentration but the trend was not statistically
      significant. The CR(eq) for (137)Cs was one to two orders of magnitude lower than
      previously reported CR(wo-soil) values (based on field data with much less
      contaminated soil), that for (85)Sr was comparable with other reported values and
      for (65)Zn was less two to three orders of magnitude lower than CR(wo-soil)
      values for stable zinc. The estimated k (d(-1)) values ranged from 9 * 10(-2) to
      1.4 * 10(-1) for (137)Cs, 7 * 10(-2) to 2 * 10(-1) for (85)Sr, and 6 * 10(-2) to
      1.8 * 10(-1) for (65)Zn, and did not show a relationship with soil activity
      concentration. The effect of CR(eq) on the total dose rate was insignificant for
      (137)Cs or (65)Zn because external dose rates to the soil dwelling earthworms due
      to these radionuclides were much greater than the internal dose rate. In
      contrast, the total dose from (90)Sr was determined by the internal dose rate and
      therefore proportional to the CR(eq).

PMID- 22948030
TI  - Counting protein molecules using quantitative fluorescence microscopy.
AB  - In recent years, quantification of absolute protein numbers in cellular
      structures using fluorescence microscopy has become a reality. Two popular
      methods are available to a broad range of researchers with minimal equipment and
      analysis requirements: stepwise photobleaching to count discrete changes in
      intensity from a small number of fluorescent fusion proteins, and comparing the
      fluorescence intensity of a protein to a known in vivo or in vitro standard. This
      review summarizes the advantages and disadvantages of each method, and gives
      recent examples of each that answer important questions in their respective
      fields. We also highlight new counting methods that could become widely available
      in the future.

PMID- 22948031
TI  - How selection for reproduction or foundation for longevity could have affected
      blood lymphocyte populations of rabbit does under conventional and heat stress
      conditions.
AB  - The present work characterises how selection for reproduction (by comparing two
      generations - 16th and 36th - of the V line selected for litter size at weaning)
      or foundation for reproductive longevity (the LP line) can affect the blood
      lymphocytes populations of reproductive rabbit does under normal [conventional
      housing, average daily minimum and maximum temperatures of 14 degrees C and 20
      degrees C, respectively] and heat stress conditions [climatic chamber, 25 degrees
      C and 36 degrees C] from the first to the second parturition. Housing under heat
      stress conditions significantly reduced the B lymphocytes counts in female
      rabbits (-34 * 10(6)/L; P<0.05). The highest lymphocytes population value in
      blood (total, T CD5(+), CD4(+) and CD8(+)) was noted at the first parturition,
      while the B lymphocytes count was significantly lower at the second parturition (
      61 * 10(6)/L; P<0.05). Selection for litter size at weaning (V females) reduced
      the average counts of total and B lymphocytes in blood (-502 and -60 * 10(6)/L,
      respectively; P<0.01), mainly because these populations in V36 females
      continuously lowered from the first to the second parturition under normal
      housing conditions. Thus, more selected females (V36) at the second parturition
      showed significantly lower counts in blood for total, T CD5(+) and CD25(+)
      lymphocytes (-1303, -446 and -33 * 10(6)/L, respectively; P<0.05). The main
      differences in blood counts between V36 and V16 females disappeared when housed
      under heat stress conditions, except for T CD5(+) and CD25(+), which
      significantly increased (T CD5(+): +428 * 10(6)/L; CD25(+): +41 * 10(6)/L;
      P<0.01) in the V16 vs. V36 females on day 10 post-partum. Under normal
      conditions, no differences between LP and V36 females were found for most
      lymphocyte populations; only higher counts were noted in CD25(+) (+20 * 10(6)/L;
      P<0.05) for LP females. However, the lymphocytes counts [especially total (+1327
      * 10(6)/L; P<0.01) and T CD5(+) (+376 * 10(6)/L; P<0.10)] of LP females increased
      under heat vs. normal conditions when lymphocytes populations presented the
      lowest values (second parturition), while V36 females' counts remained
      invariable. Positive correlations were found between feed intake (r=+0.51;
      P<0.001) and females' perirenal fat thickness (r=+0.40; P<0.001) with B
      lymphocytes counts in the blood of primiparous rabbit females in the week 2 of
      lactation. These results indicate that selection for litter size at weaning might
      diminish their immune system's response and adaptation capacity, while the
      foundation for reproductive longevity criteria leads to more robust rabbit
      females as they present greater modulation under heat stress conditions when the
      immune system is affected.

PMID- 22948032
TI  - Efficacy and patient-reported outcomes of a new mometasone cream treating atopic
      eczema.
AB  - This double-blind controlled phase II study was conducted to compare a newly
      developed formulation of mometasone furoate with a water content of 33%
      (Monovo(r) Cream) and with a smooth consistency versus the commercially available
      fatty cream of mometasone furoate (Ecural(r) Fettcreme) in terms of efficacy,
      cosmetic properties, and patients' acceptance. In 20 patients with mild to
      moderate atopic eczema, the preparations were tested intraindividually in a
      randomized mode and in two comparable lesion areas. Both preparations were
      equally effective and well tolerated. Due to improved cosmetic properties, the
      new formulation was preferred by the patients when asked for preferential use.
      Quality of life could be improved by treating with both preparations.

PMID- 22948033
TI  - Near-field microwave scanning probe imaging of conductivity inhomogeneities in
      CVD graphene.
AB  - We have performed near-field scanning microwave microscopy (SMM) of graphene
      grown by chemical vapor deposition. Due to the use of probe-sample capacitive
      coupling and a relatively high ac frequency of a few GHz, this scanning probe
      method allows mapping of local conductivity without a dedicated counter
      electrode, with a spatial resolution of about 50 nm. Here, the coupling was
      enabled by atomic layer deposition of alumina on top of graphene, which in turn
      enabled imaging both large-area films, as well as micron-sized islands, with a
      dynamic range covering a low sheet resistance of a metal film and a high
      resistance of highly disordered graphene. The structures of graphene grown on Ni
      films and Cu foils are explored, and the effects of growth conditions are
      elucidated. We present a simple general scheme for interpretation of the contrast
      in the SMM images of our graphene samples and other two-dimensional conductors,
      which is supported by extensive numerical finite-element modeling. We further
      demonstrate that combination of the SMM and numerical modeling allows
      quantitative information about the sheet resistance of graphene to be obtained,
      paving the pathway for characterization of graphene conductivity with a sub-100
      nm special resolution.

PMID- 22948034
TI  - A filtering strategy identifies FOXQ1 as a potential effector of lamin A
      dysfunction.
AB  - Small increases in the expression of wild-type prelamin A are sufficient to
      recapitulate the reduced cell proliferation and altered nuclear membrane
      morphology observed in cells expressing progerin, the mutant lamin A associated
      with progeria. We hypothesized that the manifestation of these phenotypes in
      cells expressing elevated levels of wild-type prelamin A or progerin is caused by
      the same molecular effectors, which play a central role in the onset of the
      progeroid phenotype. To experimentally test this hypothesis, we compared the
      transcriptomes of isogenic diploid fibroblasts expressing progerin or elevated
      levels of wild-type prelamin A with that of wild-type fibroblasts. We
      subsequently used the reversion towards normal of two phenotypes, reduced cell
      growth and dismorphic nuclei, by treatment with farnesyltransferase inhibitor
      (FTI) or overexpression of ZMPSTE24, as a filtering strategy to identify genes
      linked to the onset of these two phenotypes. Through this analysis we identified
      the gene encoding for the transcription factor FOXQ1, as a gene whose expression
      is induced in both cells expressing progerin and elevated levels of wild-type
      prelamin A, and subsequently reduced in both cell types upon conditions that
      ameliorate the phenotypes. We overexpressed FOXQ1 in normal fibroblasts and
      demonstrated that increased levels of this factor lead to the development of both
      features that were used in the filtering strategy. These findings suggest a
      potential link between this transcription factor and cell dysfunction induced by
      altered prelamin A metabolism.

PMID- 22948035
TI  - Sea urchin coelomocytes are resistant to a variety of DNA damaging agents.
AB  - Increasing anthropogenic activities are creating environmental pressures that
      threaten marine ecosystems. Effective environmental health assessment requires
      the development of rapid, sensitive, and cost-effective tools to predict negative
      impacts at the individual and ecosystem levels. To this end, a number of
      biological assays using a variety of cells and organisms measuring different end
      points have been developed for biomonitoring programs. The sea urchin
      fertilization/development test has been useful for evaluating environmental
      toxicology and it has been proposed that sea urchin coelomocytes represent a
      novel cellular biosensor of environmental stress. In this study we investigated
      the sensitivity of coelomocytes from the sea urchin Lytechinus variegatus to a
      variety of DNA-damaging agents including ultraviolet (UV) radiation, hydrogen
      peroxide (H(2)O(2)), methylmethane sulfonate (MMS) and benzo[a]pyrene (BaP).
      LD(50) values determined for coelomocytes after 24h of exposure to these DNA
      damaging agents indicated a high level of resistance to all treatments.
      Significant increases in the formation of apurinic/apyrimidinic (AP or abasic)
      sites in DNA were only detected using high doses of H(2)O(2), MMS and UV
      radiation. Comparison of sea urchin coelomocytes with hemocytes from the
      gastropod mollusk Aplysia dactylomela and the decapod crustacean Panulirus argus
      indicated that sensitivity to different DNA damaging agents varies between
      species. The high level of resistance to genotoxic agents suggests that DNA
      damage may not be an informative end point for environmental health assessment
      using sea urchin coelomocytes however, natural resistance to DNA damaging agents
      may have implications for the occurrence of neoplastic disease in these animals.

PMID- 22948036
TI  - Effect of ursodeoxycholic acid administration after liver transplantation on
      serum liver tests and biliary complications: a randomized clinical trial.
AB  - BACKGROUND/AIMS: Endogenous hydrophobic bile acids are suspected to be one of the
      pathogenetic factors of biliary complications after orthotopic liver
      transplantation (OLT). This study was designed to investigate the effects of
      hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum
      liver tests and the incidence of biliary complications. METHODS: 112 adult
      patients undergoing OLT from donation after cardiac death (DCD) were randomized
      to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients).
      Serum liver tests and serum bile acids of all patients and biliary bile acids in
      patients with T-tube drainage were determined during the 4 weeks after OLT.
      Biliary complications as well as patient and graft survival were analyzed during
      a mean follow-up of 41.6 months. RESULTS: UDCA treatment decreased ALT, AST and
      GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge
      and casts within the 1st year (p < 0.05). However, no differences in the
      incidence of other biliary complications as well as 1-, 3- and 5-year graft and
      patient survival were observed. CONCLUSIONS: UDCA administration early after DCD
      OLT improves serum liver tests and decreases the incidence of biliary sludge and
      casts within the 1st postoperative year but does not affect overall outcome up to
      5 years after OLT.

PMID- 22948037
TI  - H.J. Muller's contributions to mutation research.
AB  - H. J. Muller is best known for his Nobel Prize work on the induction of mutations
      by ionizing radiation. Geneticists are less familiar with his contributions to
      mutation and how he related the process of mutagenesis to the gene and
      distinguished gene mutations from other genetic and epigenetic events such as
      polyploidy, chromosome rearrangements, and position effects. The hallmark of
      Muller's contributions is his design of genetic stocks to solve genetic problems
      and allow experimentation to reveal new phenomena. In this review I relate
      Muller's personality to his teaching and research and present a history of
      Muller's ideas on mutation from his first days in Morgan's fly lab to his final
      thoughts on what became called "Muller's ratchet", a term he did not get to enjoy
      because it was coined seven years after his death.

PMID- 22948038
TI  - Nrf2-Keap1 antioxidant defense and cell survival signaling are upregulated by
      17beta-estradiol in homocysteine-treated dopaminergic SH-SY5Y cells.
AB  - BACKGROUND AND AIMS: A recent neuroimaging study discovered the neurotoxicity
      effects of homocysteine (Hcy), which is only seen in elderly women. Estrogens
      exert a variety of actions on brain function that influence cognitive function,
      mood, and neuroprotection. The Kelch-like ECH-associated protein 1
      (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant defense
      pathway has been well-known to afford neuroprotection. Here, we first demonstrate
      the roles of Nrf2-Keap1 in 17beta-estradiol (E2) cytoprotection and Hcy toxicity
      and the protective mechanisms of E2 on Hcy cytotoxicity in human dopaminergic SH
      SY5Y cells. METHODS: Cell viability was determined by trypan blue method. Protein
      expression was determined by Western blot analysis. Superoxide dismutase (SOD)
      activity was determined by ELISA. Reactive oxygen species (ROS) production was
      determined by flow cytometry. RESULTS: In Hcy-treated SH-SY5Y cells, E2 increased
      cell viability, attenuated ROS production, activated Akt signaling and inhibited
      glycogen synthase kinase-3beta (GSK-3beta), a kinase known to participate in
      neurodegeneration. Moreover, E2 treatment led to Nrf2 dissociation from Keap1,
      the main negative regulator of Nrf2 activity in the cytoplasm, and increased the
      protein level of Nrf2 in the nucleus, with a significant increase in HO-1
      expression and SOD activity in Hcy-treated cells. E2-induced Nrf2 activation was
      attenuated by the PI3K inhibitor LY294002 and the estrogen receptor antagonist
      ICI 182,780. Further, E2 decreased Hcy-induced apoptotic death by upregulating
      the antiapoptotic protein Bcl-2, decreasing cytochrome c release from
      mitochondria, and attenuating apoptotic cascade activation (Bax, caspase-9, and
      caspase-3). CONCLUSION: E2 activates cell survival signaling and Nrf2-Keap1
      antioxidant defense pathway and attenuates Hcy cytotoxicity.

PMID- 22948039
TI  - A review: Nursing of intensive care unit delirium.
AB  - The aim of this article was to review the current literature in relation to the
      nursing of intensive care unit (ICU) delirium. In particular, we discuss the
      definition and frequency, clinical features, risk factors, the adverse effects
      associated with instruments for assessing delirium, as well as prevention and
      nursing for delirium patients. Critically ill patients are at a greater risk of
      developing delirium, and delirium is a growing problem in the ICU. Most
      physicians and nurses regarded delirium as an inconvenient problem, both for
      patient and for personnel. Routine screening of all patients in the ICU for the
      presence of delirium is crucial to its successful management. Nurses are on the
      front line to detect, manage, and even prevent ICU delirium.

PMID- 22948040
TI  - Development and validation of a disease-specific scale to assess psychosocial
      well-being of patients living with unruptured intracranial aneurysm.
AB  - Although the detection rate for unruptured intracranial aneurysm (UIA) has
      improved since the 1990s, the quality of life and psychosocial status of patients
      living with UIA have been negatively affected. However, a comprehensive
      assessment tool for UIA patients is still awaited. This study aimed to develop
      and validate a disease-specific scale to assess UIA patients' psychosocial well
      being in their daily lives. On the basis of previous qualitative research, 52
      items on a six-dimension scale were generated. After a pilot study, statistical
      analysis was conducted to examine construct validity-including convergent
      validity, discriminant and known-group validity, and internal reliability.
      Between 2010 and 2011, 124 patients across three hospitals in Japan were tested
      using a tentative scale. As a result of exploratory factor analysis, we
      identified 25 items based on five conceptually derived dimensions (psychological
      stability, trust in healthcare resources, satisfaction with the decision-making
      process, positive perception of self-management, and confidence in UIA knowledge)
      as a final psychosocial well-being scale for UIA patients (UIA-PW scale).
      Cronbach's alpha coefficients for each subscale ranged between .76 and .90, with
      .83 for the total score, which indicated satisfactory internal consistency. The
      total score for the UIA-PW scale correlated significantly with the existing
      quality of life and mental health scales, but it is important to note that
      psychological stability and positive perception of self-management were
      negatively correlated. Although additional investigation is needed, the UIA-PW
      scale shows reasonable validity and reliability in assessing psychosocial well
      being of patients living with UIA.

PMID- 22948041
TI  - Gate dependent photo-responses of carbon nanotube field effect phototransistors.
AB  - Gate dependent photoconductivity of carbon nanotube (CNT) field effect
      phototransistors (FEPs) was systematically investigated in this study. The photo
      response comparisons of CNT FEPs with symmetric and asymmetric metal structures
      connecting to the same CNT revealed that the gate effect contributed to a
      sensitivity improvement with a lower dark current, a higher photocurrent, and an
      enhanced photovoltage. A functionalized asymmetric FEP, fabricated by partially
      doping the CNT utilizing a polyethylene imine (PEI) polymer, verified that FEPs
      delivered a better performance by using asymmetric structures. A multi-gate FEP,
      with three pairs of side-gates that can electrostatically dope different sections
      of a CNT independently, was fabricated to examine the gate structure dependent
      photo-responses. Experimental measurements showed an unconventional photocurrent
      improvement that was weakly dependent on the gate location, which was attributed
      to the unique charge distribution of one-dimensional semiconductors.

PMID- 22948042
TI  - Highly hydrophilic thin-film composite forward osmosis membranes functionalized
      with surface-tailored nanoparticles.
AB  - Thin-film composite polyamide membranes are state-of-the-art materials for
      membrane-based water purification and desalination processes, which require both
      high rejection of contaminants and high water permeabilities. However, these
      membranes are prone to fouling when processing natural waters and wastewaters,
      because of the inherent surface physicochemical properties of polyamides. The
      present work demonstrates the fabrication of forward osmosis polyamide membranes
      with optimized surface properties via facile and scalable functionalization with
      fine-tuned nanoparticles. Silica nanoparticles are coated with superhydrophilic
      ligands possessing functional groups that impart stability to the nanoparticles
      and bind irreversibly to the native carboxyl moieties on the membrane selective
      layer. The tightly tethered layer of nanoparticles tailors the surface chemistry
      of the novel composite membrane without altering the morphology or water/solute
      permeabilities of the membrane selective layer. Surface characterization and
      interfacial energy analysis confirm that highly hydrophilic and wettable membrane
      surfaces are successfully attained. Lower intermolecular adhesion forces are
      measured between the new membrane materials and model organic foulants,
      indicating the presence of a bound hydration layer at the polyamide membrane
      surface that creates a barrier for foulant adhesion.

PMID- 22948044
TI  - Extensive molecular mapping of TCRalpha/delta- and TCRbeta-involved chromosomal
      translocations reveals distinct mechanisms of oncogene activation in T-ALL.
AB  - Chromosomal translocations involving the TCR loci represent one of the most
      recurrent oncogenic hallmarks of T-cell acute lymphoblastic leukemia (T-ALL) and
      are generally believed to result from illegitimate V(D)J recombination events.
      However, molecular characterization and evaluation of the extent of recombinase
      involvement at the TCR-oncogene junction has not been fully evaluated. In the
      present study, screening for TCRbeta and TCRalpha/delta translocations by FISH
      and ligation-mediated PCR in 280 T-ALLs allowed the identification of 4
      previously unreported TCR-translocated oncogene partners: GNAG, LEF1, NKX2-4, and
      IL2RB. Molecular mapping of genomic junctions from TCR translocations showed that
      the majority of oncogenic partner breakpoints are not recombinase mediated and
      that the regulatory elements predominantly used to drive oncogene expression
      differ markedly in TCRbeta (which are exclusively enhancer driven) and
      TCRalpha/delta (which use an enhancer-independent cryptic internal promoter)
      translocations. Our data also imply that oncogene activation takes place at a
      very immature stage of thymic development, when Ddelta2-Ddelta3/Ddelta3-Jdelta1
      and Dbeta-Jbeta rearrangements occur, whereas the bulk leukemic maturation arrest
      occurs at a much later (cortical) stage. These observations have implications for
      T-ALL therapy, because the preleukemic early thymic clonogenic population needs
      to be eradicated and its disappearance monitored.

PMID- 22948043
TI  - Age-adjusted recipient pretransplantation telomere length and treatment-related
      mortality after hematopoietic stem cell transplantation.
AB  - Telomere attrition induces cell senescence and apoptosis. We hypothesized that
      age-adjusted pretransplantation telomere length might predict treatment-related
      mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between
      2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling
      donors after myeloablative conditioning regimens, mainly for hematologic
      malignancies (n = 153). Blood lymphocytes' telomere length was measured by real
      time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere
      lengths were analyzed for correlation with clinical outcomes. After age
      adjustment, patients' telomere-length distribution was similar among all 4
      quartiles except for disease stage. There was no correlation between telomere
      length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years
      (95% confidence interval [CI], 54-70). After a median follow-up of 51 months
      (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely
      correlated with telomere length. TRM in patients in the first (lowest telomere
      length) quartile was significantly higher than in patients with longer telomeres
      (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI,
      .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI;
      0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age
      adjusted recipients' telomere length is an independent biologic marker of TRM
      after HSCT.

PMID- 22948045
TI  - How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing.
AB  - Amyloidosis is a rare group of diseases characterized by deposition of amyloid
      fibrils in soft tissues. More than 28 types of amyloid have been identified. They
      all share common ultrastructural and chemical characteristics. Treatments are
      available for many types but are type specific. Therefore, confirmation and
      typing of amyloid are essential before initiating treatment. Monoclonal protein
      studies should be performed on suspected cases, but the diagnosis requires a
      tissue biopsy. Congo red stain and electron microscopy are helpful to
      discriminate between amyloid and other pathologic fibrils. Once amyloid is
      confirmed, typing should be performed. Immunofluorescence and
      immunohistochemistry are frequently used and are helpful, but this approach has
      limitations, such as availability, specificity and sensitivity of commercial
      antibodies. Genetic mutational analysis is vital for ruling in and out hereditary
      amyloidoses but is unhelpful in nonmutated forms. The most advanced technique of
      amyloid typing is laser microdissection followed by mass spectrometry. Using
      proteomics, laser microdissection followed by mass spectrometry can directly
      identify proteins with or without mutations. Finally, imaging studies, such as
      cardiac MRI with gadolinium and (123)I-labeled SAP scintigraphy not only assist
      in evaluation of patients with known amyloidosis but cardiac MRI has detected
      amyloid in patients previously unsuspected of the disease.

PMID- 22948046
TI  - Regulation of plasmacytoid dendritic cell responses by PIR-B.
AB  - Plasmacytoid dendritic cells (PDCs) produce type I interferons (IFNs) in response
      to viral nucleic acids to exert antiviral immunity. However, PDCs are related to
      the progress and severity of autoimmune diseases, such as systemic lupus
      erythematosus, because they respond to host DNA. Therefore, the regulation of PDC
      activation is critical for maintaining adequate immune responses. Here we show
      that an inhibitory major histocompatibility complex class I receptor, paired
      immunoglobulin-like receptor B (PIR-B), suppressed Fms-like tyrosine kinase 3
      ligand-induced PDC differentiation in BM cells, as well as Toll-like receptor 9
      mediated IFN-alpha production by PDCs, through the dephosphorylation of
      STAT1/STAT2. In particular, PIR-B inhibited IFN-alpha-mediated STAT
      phosphorylation, suggesting that PIR-B negatively regulates the positive feedback
      mechanism of IFN-alpha secretion triggered by Toll-like receptor 9. These results
      demonstrate a novel regulatory role for PIR-B in PDCs.

PMID- 22948047
TI  - Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a
      preclinical baboon model of acquired thrombotic thrombocytopenic purpura.
AB  - ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits
      the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a
      crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In
      the present study, we report the efficacy and safety profile of ALX-0681 in a
      baboon model of acquired TTP. In this model, acute episodes of TTP are induced by
      administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the
      rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After
      induction of TTP, platelet counts also rapidly recovered on administration of ALX
      0681. This effect was corroborated by the full neutralization of VWF activity.
      The schistocytic hemolytic anemia was also halted and partially reversed by ALX
      0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign
      of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under
      conditions of thrombocytopenia was not linked with an excessive bleeding risk.
      The results obtained in this study demonstrate that ALX-0681 can successfully
      treat and prevent the most important hallmarks of acquired TTP without evidence
      of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new
      therapeutic option for acquired TTP in the clinical setting.

PMID- 22948048
TI  - Acute silent cerebral ischemia and infarction during acute anemia in children
      with and without sickle cell disease.
AB  - We hypothesized that the silent cerebral infarcts (SCI), which affect up to 40%
      of children with sickle cell disease (SCD), could occur in the setting of acute
      anemic events. In a prospective observational study of children with and without
      SCD hospitalized for an illness associated with acute anemia, we identified acute
      silent cerebral ischemic events (ASCIE) in 4 (18.2%) of 22 with SCD and in 2
      (6.7%) of 30 without SCD, using diffusion-weighted magnetic resonance imaging.
      Children with ASCIE had lower hemoglobin concentration than those without (median
      3.1 vs 4.4 g/dL, P = .003). The unique temporal features of stroke on diffusion
      weighted magnetic resonance imaging permit estimation of incidence rates for
      ASCIE of 421 (95% confidence interval, 155-920) per 100 patient-years during
      acute anemic events for all patients. For children with SCD, the estimated
      incidence was 663 (95% confidence interval, 182-1707) which is much higher than
      previously reported. Acute anemic events are common in children with SCD and
      prevalence could partially account for the high SCI. Some ASCIE (1 of 4 in our
      study) may be reversible. Alterations in management may be warranted for children
      with severe anemia to identify unrecognized ischemic brain injury that may have
      permanent neurocognitive sequelae.

PMID- 22948050
TI  - [More happy news will be in the next issue; our new place at the SCI-E].

PMID- 22948049
TI  - Tumor-associated macrophages predict inferior outcomes in classic Hodgkin
      lymphoma: a correlative study from the E2496 Intergroup trial.
AB  - Increased tumor-associated macrophages (TAMs) are reported to be associated with
      poor prognosis in classic Hodgkin lymphoma (CHL). We investigated the prognostic
      significance of TAMs in the E2496 Intergroup trial, a multicenter phase 3
      randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally
      extensive and advanced stage CHL. Tissue microarrays were constructed from
      formalin-fixed, paraffin-embedded tumor tissue and included 287 patients.
      Patients were randomly assigned into training (n = 143) and validation (n = 144)
      cohorts. Immunohistochemistry for CD68 and CD163, and in situ hybridization for
      EBV-encoded RNA were performed. CD68 and CD163 IHC were analyzed by computer
      image analysis; optimum thresholds for overall survival (OS) were determined in
      the training cohort and tested in the independent validation cohort. Increased
      CD68 and CD163 expression was significantly associated with inferior failure-free
      survival and OS in the validation cohort. Increased CD68 and CD163 expression was
      associated with increased age, EBV-encoded RNA positivity, and mixed cellularity
      subtype of CHL. Multivariate analysis in the validation cohort showed increased
      CD68 or CD163 expression to be significant independent predictors of inferior
      failure-free survival and OS. We demonstrate the prognostic significance of TAMs
      in locally extensive and advanced-stage CHL in a multicenter phase 3 randomized
      controlled clinical trial.

PMID- 22948051
TI  - A review of scalp camouflaging agents and prostheses for individuals with hair
      loss.
AB  - Hair loss is a common problem for both men and women and may impact negatively on
      self-esteem. A variety of medical and surgical treatment options are available
      depending on the type of alopecia. Many patients also seek the advice of their
      physicians about options to hide or reduce the appearance of hair loss with hair
      prostheses (wigs, hairpieces, and extensions) or hair camouflaging agents (hair
      fibers, powder cakes, lotions, sprays, hair crayons, and scalp tattooing).
      Herein, we review current methods to hide or reduce the appearance of hair loss
      and discuss their associated costs, advantages, and disadvantages. Knowledge of
      products available to cover scalp, eyebrow, and eyelash hair loss may not only
      better equip clinicians to respond to questions from concerned patients, but may
      provide additional options to help these patients best cope with their hair loss.

PMID- 22948052
TI  - Herpes zoster vaccine awareness among people >= 50 years of age and its
      implications on immunization.
AB  - Herpes zoster (HZ) vaccine was recently approved for adults >= 50 years of age
      and has been shown to reduce the incidence of zoster, postherpetic neuralgia
      (PHN), and associated healthcare costs. However, currently HZ immunization is sub
      optimal. We examined awareness of HZ and of the HZ vaccine. Information was
      gathered via a one-page survey given to patients >= 50 years of age presenting at
      the dermatology clinic. From the surveyed population of 1000 individuals, the HZ
      vaccination rate was 11.9 percent. Vaccination coverage was highest for the >= 70
      age group (18.3%), followed by age groups 60-69 (8.9%) and 50-59 (1.4%).
      Individuals with female gender, older age (>= 70 years), higher level of
      education (college and beyond), retired employment status, memory of chickenpox,
      knowledge of shingles, and history of shingles and influenza vaccination in the
      past year all were more likely to have heard of and have received the HZ vaccine
      (except female gender, education level, and awareness of shingles). Our study
      suggests lack of awareness to be a significant factor in non-immunization with
      zoster vaccine. Targeting adults in younger age groups and minorities would be
      beneficial towards increasing zoster vaccine awareness and thus preventing herpes
      zoster and its many complications.

PMID- 22948053
TI  - Extramammary Paget disease of the penis as a manifestation of recurrent
      transitional cell carcinoma.
AB  - Extramammary Paget disease (EMPD) mainly affects elderly women in areas with
      apocrine glands. Only 10 cases have been reported to involve the penis in
      patients with underlying transitional cell carcinoma of the bladder. Herein we
      report a patient with EMPD of the penis after radical cystectomy.

PMID- 22948054
TI  - Sarcoidosis-induced alopecia.
AB  - Cutaneous sarcoidosis of the scalp may induce scarring alopecia, which clinically
      resembles other forms of primary cicatricial alopecia. Differentiation via
      histologic evaluation is necessary because sarcoidosis demonstrates classical non
      caseating granulomas. Review of the literature reveals that sarcoidosis-induced
      alopecia occurs more commonly in black females age 23 to 78, with the majority of
      patients having coexisting facial sarcoidosis with pulmonary and lymph node
      involvement. Given the strong association between sarcoidal alopecia and systemic
      sarcoidosis, evaluation of the patient is indicated if alopecia is the initial
      presenting manifestation.

PMID- 22948055
TI  - A case of porokeratosis plantaris palmaris et disseminata and literature review.
AB  - Porokeratosis plantaris palmaris et disseminata (PPPD) is a quite rare variant of
      porokeratosis. We report a 56-year-old male patient. He first noted brownish,
      asymptomatic, annular macules scattered on the trunk and extremities at about age
      31 and these skin lesions, continued to increase in number. Ten years prior to
      presentation, similar lesions appeared on the palms. About one to two years ago,
      the patient noted painful wart-like, keratotic punctuate papules 2-3 mm in
      diameter on the soles, which disturbed walking. Histological examination showed
      the characteristic feature of the cornoid lamella. The family tree of this
      patient showed an autosomal dominant mode of transmission. We review sixteen
      typical cases of PPPD previously reported in the English literature.

PMID- 22948056
TI  - Syringitis: a clue to herpes infection.
AB  - Herpes simplex virus (HSV) is a member of the herpes virus family that commonly
      affects the skin. Typical histopathologic findings are usually limited to the
      epidermis and include intraepidermal vesicles or ulceration and epidermal
      necrosis. More specific findings in herpes virus infection include enlarged and
      pale keratinocytes, with steel-gray nuclei and margination of chromatin at the
      edge of the nucleus and ballooning degeneration. Although histopathologic changes
      may occasionally involve the hair follicles or sebaceous glands, it is very rare
      to find HSV involving the eccrine glands. We present a case of a 13-month-old
      child with a large body burn diagnosed with HSV (in the absence of the epidermis)
      by the presence of syringitis with herpetic features in the absence of the
      epidermis to aid in diagnosis.

PMID- 22948057
TI  - Radiofrequency ablation: a safe and economical modality in treatment of Brooke
      Spiegler syndrome.
AB  - Brooke-Spiegler syndrome is an uncommon disease. Patients have a predisposition
      to develop cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas,
      spiradenomas, trichoblastomas, basal cell carcinomas, follicular cysts, and
      organoid nevi. Malignant transformation of preexisting tumors also occurs in
      these individuals. Various techniques have been used for the treatment of
      trichoepitheliomas and cylindromas including excision, electrocautery, carbon
      dioxide laser ablation, cryosurgery, and radiotherapy. In our case, cylindromas
      were ablated by radiofrequency in multiple sittings. Trichoepitheliomas were
      ablated using coagulation mode with power # 3 to 3.5. Cosmetically acceptable
      results were obtained in 100 percent of the cylindromas and 70 percent of the
      trichoepitheliomas (Visual Analog Scale). The radiofrequency ablation technique
      under different modes can be used in both large tumors as well as smaller ones,
      especially in developing countries because it is very cost effective and easily
      accessible.

PMID- 22948058
TI  - A case of multiple epithelioid angiomatous nodules.
AB  - Cutaneous epithelioid angiomatous nodule (CEAN) is a distinct type of epithelioid
      vascular tumor that is usually solitary. Herein we present a 31-year-old man with
      multiple, rapidly growing nodules on the scalp.

PMID- 22948059
TI  - Unknown: a warm, painful nodule on the back.
AB  - A 67-year-old man presented with a complaint of a painful nodule on his back for
      approximately two months. On exam, a violaceous, firm, warm, indurated nodule
      measuring 3.5 x 2 cm was observed. Nine months prior to presentation, he was
      diagnosed with a moderately differentiated squamous cell carcinoma (SCC) of the
      left upper lobe (stage 1b), which was removed via video-assisted thoracoscopic
      wedge resection. Diagnosis of metastatic SCC secondary to traumatic seeding at a
      trocar port site was made. To our knowledge, this has not been previously
      described in the literature.

PMID- 22948060
TI  - Pili annulati--what about racial distribution?
AB  - Pili annulati is a rare hair shaft abnormality and, as far as we know, there are
      no published data on pili annulati's racial distribution. To our knowledge, this
      is the first case reported in an African-American patient.

PMID- 22948061
TI  - Papillary dermal elastosis.
AB  - We recently came across the article "Papillary dermal elastosis" by Newlove et al
      published in the October 2011 edition of Dermatology Online Journal. In this
      paper, the authors described what they interpreted to be the second case of
      papillary dermal elastosis, an entity we had first identified in 2009. Upon
      further reading of their histopathologic and clinical description, we believe
      this case is more consistent with the diagnosis of pseudoxanthoma elasticum-like
      papillary dermal elastolysis (PXE-PDE).

PMID- 22948062
TI  - Lamotrigine induced subacute cutaneous lupus erythematous.
AB  - A 48-year-old woman developed drug-induced subacute lupus erythematosus while
      taking lamotrigine. The eruption resolved after discontinuance of lamotrigine,
      suggesting this drug as the cause.

PMID- 22948063
TI  - Vesico-bullous subacute cutaneous lupus erythematosus--an uncommon entity
      successfully treated with dapsone and hydroxychloroquine.
AB  - Vesico-bullous subacute cutaneous lupus erythematosus is an uncommon and severe
      presentation. The authors report an exuberant case of vesico-bullous subacute
      cutaneous lupus erythematosus successfully treated with dapsone and
      hydroxychloroquine.

PMID- 22948064
TI  - An adult case of severe hand-foot-mouth disease accompanying persistent fever and
      systemic arthritis.
AB  - This paper reports a case of adult HFMD with vesicles scattered on the whole body
      and severe oral lesions. In addition, a long-lasting elevated level of C-reactive
      protein (CRP) was a feature of this case. Our case is unusual for HFMD with long
      lasting joint pain and high fever.

PMID- 22948065
TI  - Exuberant cutaneous ulcers on the buttocks caused by multi-resistant Klebsiella
      pneumoniae.
AB  - Cutaneous infection develops because of environmental and local factors, host
      immunity, and organism adherence and virulence. The authors report a case of
      exuberant cutaneous ulcers on the buttocks of a diabetic patient. Microbiologic
      examination allowed the identification of Klebsiella pneumoniae and complete
      resolution was achieved with the appropriate antibiotic.

PMID- 22948066
TI  - An unusual case of isolated sixth cranial nerve palsy in leprosy.
AB  - Cranial nerve involvement is not common in leprosy. The fifth and seventh cranial
      nerves are the most commonly affected in leprosy. Herein we present a patient
      with Hansen disease (BL) with type I reaction who developed isolated involvement
      of the sixth cranial nerve leading to lateral rectus muscle palsy. He responded
      to timely anti-reactional therapy and it produced a good response. Careful
      observation of patients with lepra reaction is needed to avoid damage to
      important organs.

PMID- 22948067
TI  - Gender difference in the association of hyperuricemia with chronic kidney disease
      in southern China.
AB  - BACKGROUND: The effect of hyperuricemia on chronic kidney disease (CKD) is
      controversial, and little is known about gender as it relates to hyperuricemia
      and CKD. METHODS: This was a cross-sectional study of 7,053 adults in the general
      Chinese population in Southern China using a multi-stage stratified sampling
      method. In which associations between hyperuricemia and indicators of CKD
      (defined by albuminuria (urinary albumin-to -creatinine ratio >= 30 mg/g) or
      decreased modified MDRD equation estimated GFR (<60 ml/min per 1.73 m2) were
      tested using multivariate logistic regression. RESULTS: After adjustment for
      potential confounders, hyperuricemia was associated with increased risk of
      reduced renal function and CKD but not albuminuria, with odds ratios (ORs) (95%
      CI) of 4.39 (3.38-5.70, P < 0.001), 1.54 (1.31-1.82, P <0.001) and 0.96 (0.78
      1.17, P =0.671), respectively. The interaction between gender and hyperuricemia
      with CKD was significant (P =0.010); and stratified analysis showed a stronger
      association of hyperuricemia with CKD in males (OR (95% CI): 2.04 (1.56-2.67), P
      < 0.001) than in females (1.45 (1.17-1.80), P = 0.001). CONCLUSIONS: We observed
      an independent association of hyperuricemia with CKD that was stronger in males,
      and this independent association in male might imply some gender specific
      mechanisms. These results should be confirmed in future prospective studies.

PMID- 22948068
TI  - Later first marriage and marital success.
AB  - The research reported here used measures of marital success based on both marital
      survival and marital quality to assess how well first marriages entered at
      relatively late ages fare in comparison with those entered younger. Analysis of
      data from five American data sets indicated that the later marriages fare very
      well in survival but rather poorly in quality. The greatest indicated likelihood
      of being in an intact marriage of the highest quality is among those who married
      at ages 22-25, net of the estimated effects of time since first marriage and
      several variables that might commonly affect age at marriage and marital
      outcomes. The negative relationship beyond the early to mid-twenties between age
      at marriage and marital success is likely to be at least partially spurious, and
      thus it would be premature to conclude that the optimal time for first marriage
      for most persons is ages 22-25. However, the findings do suggest that most
      persons have little or nothing to gain in the way of marital success by
      deliberately postponing marriage beyond the mid-twenties.

PMID- 22948069
TI  - Host body microcosm and ectoparasite infracommunities: arthropod ectoparasites
      are not spatially segregated.
AB  - We studied the distribution of ectoparasite species (an ixodid tick, a chigger
      mite, 7 mesostigmate mites, 5 fleas and 3 lice) on bodies of 5 species of rodent
      hosts from the marshlands in Argentina to establish whether arthropod
      ectoparasites are segregated across body parts of the same host individual. We
      asked (a) whether an individual ectoparasite species prefers certain parts of the
      body of its host and, if yes, whether these preferences overlap among
      ectoparasite species; (b) whether ectoparasite species composition differs among
      different parts of a host's body; and (c) whether co-occurrences of ectoparasite
      species within pre-defined body parts of a host are non-random and, if yes,
      whether ectoparasites co-occur in the same body part of a host either less or
      more often than expected by chance. It was found that, in general, ectoparasite
      species were not segregated across body parts of a host. Although some
      ectoparasites preferred certain body parts, these preferences were similar among
      ectoparasites belonging to different species and/or higher taxa resulting in
      similarity among host body parts in ectoparasite species composition. In
      addition, ectoparasite species demonstrated a tendency to co-occur on the same
      body parts of a host and not to be segregated among them. It was concluded that
      the distribution of ectoparasites on the body of a small mammalian host is driven
      mainly by their interaction with the host rather than by distinct preferences or
      interactions among ectoparasite species.

PMID- 22948070
TI  - Voltage-dependent inhibition of outward Kir2.1 currents by extracellular
      spermine.
AB  - Outward currents through inward rectifier Kir2.1 channels play crucial roles in
      controlling the electrical properties of excitable cells. Extracellular
      monovalent and divalent cations have been shown to reduce outward K(+)
      conductance. In the present study, we examined whether spermine, with four
      positive charges, also inhibits outward Kir2.1 currents. We found that
      extracellular spermine inhibits steady-state outward Kir2.1 currents, an effect
      that increases as the voltage becomes more depolarizing, similar to that observed
      for intracellular spermine. However, several lines of evidence suggest that
      extracellular spermine does not inhibit outward currents by entering the
      cytoplasmic pore. Site-directed mutagenesis studies support that extracellular
      spermine directly interacts with the extracellular domain. In addition, we found
      that the voltage-dependent decay of outward Kir2.1 currents was necessary for
      inhibition by extracellular spermine. Further, a region at or near the
      selectivity filter and the cytoplasmic pore are involved in the voltage-dependent
      decay and thus in the inhibition of outward currents by extracellular spermine.
      Taken together, the data suggest that extracellular spermine bound to the mouth
      of the extracellular pore may induce an allosteric effect on voltage-dependent
      decay of outward currents, a process in which a region in the vicinity of the
      selectivity filter and cytoplasmic pore are involved. This study reveals that the
      extracellular pore domain, the selectivity filter and the cytoplasmic pore are in
      communication and this coupling is involved in modulating K(+) conduction in the
      Kir2.1 channel.

PMID- 22948071
TI  - Inducible progenitor-derived Wingless regulates adult midgut regeneration in
      Drosophila.
AB  - The ability to regenerate following stress is a hallmark of self-renewing
      tissues. However, little is known about how regeneration differs from homeostatic
      tissue maintenance. Here, we study the role and regulation of Wingless (Wg)/Wnt
      signalling during intestinal regeneration using the Drosophila adult midgut. We
      show that Wg is produced by the intestinal epithelial compartment upon damage or
      stress and it is exclusively required for intestinal stem cell (ISC)
      proliferation during tissue regeneration. Reducing Wg or downstream signalling
      components from the intestinal epithelium blocked tissue regeneration.
      Importantly, we demonstrate that Wg from the undifferentiated progenitor cell,
      the enteroblast, is required for Myc-dependent ISC proliferation during
      regeneration. Similar to young regenerating tissues, ageing intestines required
      Wg and Myc for ISC hyperproliferation. Unexpectedly, our results demonstrate that
      epithelial but not mesenchymal Wg is essential for ISC proliferation in response
      to damage, while neither source of the ligand is solely responsible for ISC
      maintenance and tissue self-renewal in unchallenged tissues. Therefore, fine
      tuning Wnt results in optimal balance between the ability to respond to stress
      without negatively affecting organismal viability.

PMID- 22948073
TI  - New neurons for 'survival of the fittest'.
AB  - Adult neurogenesis is often considered an archaic trait that has undergone a
      'phylogenetic reduction' from amphibian ancestors to humans. However, adult
      neurogenesis in the hippocampal dentate gyrus might actually be a late-evolved
      trait. In non-mammals, adult hippocampal neurogenesis is not restricted to the
      equivalents of the dentate gyrus, which also show different connectivity and
      functionality compared to their mammalian counterpart. Moving actively in a
      changing world and dealing with novelty and complexity regulate adult
      neurogenesis. New neurons might thus provide the cognitive adaptability to
      conquer ecological niches rich with challenging stimuli.

PMID- 22948078
TI  - Male and female gluteal muscle activity and lower extremity kinematics during
      running.
AB  - BACKGROUND: Patellofemoral pain is one of the most common lower extremity overuse
      injuries in runners and is significantly more common in females. This study
      evaluated differences in the timing and magnitude of gluteal muscle activity as
      well as hip and knee joint frontal and transverse plane kinematics between male
      and female runners in the context of this gender bias. METHODS: Twenty healthy
      male and 20 healthy female runners were participants. Three-dimensional lower
      extremity kinematics, and gluteus medius and gluteus maximus muscle activation
      were recorded using motion analysis and electromyography as subjects ran at 3.7
      m/s (+/-5%). Comparisons of hip and knee joint kinematic and gluteus muscle
      activation data were made using independent t-tests (alpha=0.05). FINDINGS:
      Females ran with 40% greater peak gluteus maximus activation level (P=0.028,
      effect size=0.79) and 53% greater average activation level (P=0.013, effect
      size=0.93) than males. Female runners also displayed greater hip adduction
      (P=.001, effect size=1.20) and knee abduction (P=0.011, effect size=0.87) angles
      at initial contact, greater hip adduction at peak vertical ground reaction force
      (P<0.001, effect size=1.31), and less knee internal rotation excursion than males
      (P=0.035, effect size=0.71). INTERPRETATION: Greater gluteus maximus activation
      levels during running may predispose females to earlier gluteus maximus fatigue,
      promoting altered lower extremity running kinematics thought to be associated
      with the etiology of patellofemoral pain. Gender differences in transverse and
      frontal plane hip and knee kinematics observed in this study may also contribute
      to the gender bias for patellofemoral pain among females.

PMID- 22948074
TI  - Dancing partners at the synapse: auxiliary subunits that shape kainate receptor
      function.
AB  - Kainate receptors are a family of ionotropic glutamate receptors whose
      physiological roles differ from those of other subtypes of glutamate receptors in
      that they predominantly serve as modulators, rather than mediators, of synaptic
      transmission. Neuronal kainate receptors exhibit unusually slow kinetic
      properties that have been difficult to reconcile with the behaviour of
      recombinant kainate receptors. Recently, however, the neuropilin and tolloid-like
      1 (NETO1) and NETO2 proteins were identified as auxiliary kainate receptor
      subunits that shape both the biophysical properties and synaptic localization of
      these receptors.

PMID- 22948079
TI  - The grapevine expression atlas reveals a deep transcriptome shift driving the
      entire plant into a maturation program.
AB  - We developed a genome-wide transcriptomic atlas of grapevine (Vitis vinifera)
      based on 54 samples representing green and woody tissues and organs at different
      developmental stages as well as specialized tissues such as pollen and senescent
      leaves. Together, these samples expressed ~91% of the predicted grapevine genes.
      Pollen and senescent leaves had unique transcriptomes reflecting their
      specialized functions and physiological status. However, microarray and RNA-seq
      analysis grouped all the other samples into two major classes based on maturity
      rather than organ identity, namely, the vegetative/green and mature/woody
      categories. This division represents a fundamental transcriptomic reprogramming
      during the maturation process and was highlighted by three statistical approaches
      identifying the transcriptional relationships among samples (correlation
      analysis), putative biomarkers (O2PLS-DA approach), and sets of strongly and
      consistently expressed genes that define groups (topics) of similar samples
      (biclustering analysis). Gene coexpression analysis indicated that the
      mature/woody developmental program results from the reiterative coactivation of
      pathways that are largely inactive in vegetative/green tissues, often involving
      the coregulation of clusters of neighboring genes and global regulation based on
      codon preference. This global transcriptomic reprogramming during maturation has
      not been observed in herbaceous annual species and may be a defining
      characteristic of perennial woody plants.

PMID- 22948080
TI  - Factors contributing to adverse events after ICU discharge: a survey of liaison
      nurses.
AB  - BACKGROUND: A significant number of patients experience an adverse event when
      discharged from intensive care to a ward. More than half of these events may be
      preventable with better standards of care. AIM: To explore the opinions of an
      expert group of clinicians around factors contributing to adverse events in
      patients discharged from ICU. METHOD: Online survey of Australian ICU Liaison
      Nurses (n=39) using a validated questionnaire of 25 items. RESULTS: The response
      rate was 92.8%. Key contributing factors included a lack of experienced ward
      staff, patient co-morbidities and the clinically challenging nature of many
      patients. CONCLUSION: Modifying processes of care may decrease the risk or impact
      of adverse events in this high risk patient population.

PMID- 22948081
TI  - Retinal nerve fiber thickness is reduced in sleep apnea syndrome.
AB  - OBJECTIVE: To investigate the prevalence of glaucoma, visual field abnormalities,
      as well as changes in retinal nerve fiber layer in patients with obstructive
      sleep apnea syndrome (OSAS). METHODS: In this cross-sectional study, 51 patients
      with OSAS were included. Based on apnea hypopnea index (AHI), there were 26, 6
      and 19 cases of severe (AHI?30), moderate (15?AHI<30), and mild (5?AHI<15) OSAS,
      respectively. The control group was matched for age, sex and body mass index.
      Prevalence of glaucoma and ocular hypertension as well as the following values
      were assessed and compared between two groups: best-corrected visual acuity,
      intraocular pressure, central corneal thickness (CCT), cup:disk ratio, mean
      deviation (MD), pattern standard deviation, and retinal nerve fiber layer (RNFL)
      parameters using glaucoma diagnosis measurement (GDx). RESULTS: Seven eyes (6.7%)
      had intraocular pressure (IOP)>21mmHg; of these, four eyes (3.9%) had glaucoma.
      No significant difference was detected in CCT between the two groups. IOP was
      significantly higher in the OSAS group before (p<0.001) and after (p<0.001)
      correcting for CCT. There was a significant difference between groups in MD and
      most GDx parameters including DISK (temporal-superior-nasal-inferior-temporal)
      average (p=0.002), superior average (p=0.05) and nerve fiber indicator (NFI)
      (p=0.03), where those in the patient group showed lower values. There was a
      significant positive correlation between AHI and both IOP and NFI. CONCLUSIONS:
      OSAS patients had a higher prevalence of glaucoma and ocular hypertension. OSAS
      patients also had higher IOP, worse visual field indices, and lower RNFL
      parameters compared with the control group.

PMID- 22948082
TI  - Corticosteroids plus long-acting beta2-agonists prevent double-stranded RNA
      induced upregulation of B7-H1 on airway epithelium.
AB  - BACKGROUND: Airway viral infections provoke exacerbations of asthma and chronic
      obstructive pulmonary disease. B7-H1 is a costimulatory molecule that is
      implicated in an escape mechanism of viruses from host immune systems. This
      escape may be associated with the persistence of viral infection and lead to
      exacerbation of underlying diseases. We have shown that an analog of viral double
      stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the
      expression of B7-H1 on airway epithelial cells, an effect which was
      corticosteroid-resistant. We investigated the effects of corticosteroids plus
      long-acting beta(2)-agonists (LABAs; fluticasone/salmeterol or
      budesonide/formoterol) on the expression of B7-H1. METHODS: BEAS-2B cells and
      primary airway epithelial cells were stimulated with poly IC or respiratory
      syncytial virus. The expression of B7-H1 was assessed by flow cytometry. RESULTS:
      Poly IC upregulated the expression of B7-H1, which was suppressed by high
      concentration corticosteroids but not by LABAs. The upregulation was suppressed
      by very low-concentration corticosteroids when used in combination with LABAs.
      Their combination also suppressed the virus-induced upregulation of B7-H1. Poly
      IC stimulation induced the nuclear translocation of nuclear factor KB (NF-KB).
      Inhibitors of NF-KB activation prevented the poly IC-induced upregulation of B7
      H1. Low-concentration corticosteroids in combination with LABAs enhanced the de
      novo induction of IKBalpha, the endogenous inhibitor of NF-KB activation.
      CONCLUSIONS: Fluticasone/salmeterol or budesonide/formoterol attenuate the virus
      associated upregulation of B7-H1 on airway epithelial cells via suppression of NF
      KB activation.

PMID- 22948083
TI  - Photo-stimulated resistive switching of ZnO nanorods.
AB  - Resistive switching memory devices are promising candidates for emerging memory
      technologies because they yield outstanding device performance. Storage
      mechanisms for achieving high-density memory applications have been developed;
      however, so far many of them exhibit typical resistive switching behavior from
      the limited controlling conditions. In this study, we introduce photons as an
      unconventional stimulus for activating resistive switching behaviors. First, we
      compare the resistive switching behavior in light and dark conditions to describe
      how resistive switching memories can benefit from photons. Second, we drive the
      switching of resistance not by the electrical stimulus but only by the modulation
      of photon. ZnO nanorods were employed as a model system to demonstrate photo
      stimulated resistive switching in high-surface-area nanomaterials, in which photo
      driven surface states strongly affect their photoconductivity and resistance
      states.

PMID- 22948085
TI  - Correlated evolution of gonadotropin-releasing hormone and gonadotropin
      inhibitory hormone and their receptors in mammals.
AB  - BACKGROUND: Evolutionary rate variation in genes (proteins) is manifested both
      within the species (genome) and between the species (genomes). However, the
      interdependent components of a biological system in form of a gene or a protein
      are expected to evolve in a correlated manner under a common functional
      constraint. METHODS: The phylogenetic analysis and correlation analysis of
      gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH)
      and their receptors (GnRHR and GnIHR) was conducted along with other control
      neuropeptides. RESULTS: Both neuropeptides and their receptors regulating the
      reproductive neuroendocrine axis in vertebrates exhibited a correlated evolution
      under a common physiological constraint to regulate the release of gonadotropin.
      This result supports a coordinated substitution of amino acids in the GnRH and
      the GnIH neuropeptides along with their receptors in terms of similar
      evolutionary rates and distances with similar nucleotide composition of genes.
      CONCLUSION: This is the first demonstration of the correlated evolution of two
      components of an endocrine system regulating the release of gonadotropin which
      are acting in concert for successful reproduction.

PMID- 22948084
TI  - Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of
      EZH2 in melanoma.
AB  - MicroRNAs (miRs) play a key role in cancer etiology by coordinately repressing
      numerous target genes involved in cell proliferation, migration and invasion. The
      genomic region in chromosome 9p21 that encompasses miR-31 is frequently deleted
      in solid cancers including melanoma; however the expression and functional role
      of miR-31 has not been previously studied in melanoma. Here, we queried the
      expression status and performed functional characterization of miR-31 in melanoma
      tissues and cell lines. We found that down-regulation of miR-31 was a common
      event in melanoma tumors and cell lines and was associated with genomic loss in a
      subset of samples. Down-regulation of miR-31 gene expression was also a result of
      epigenetic silencing by DNA methylation, and via EZH2-mediated histone
      methylation. Ectopic overexpression of miR-31 in various melanoma cell lines
      inhibited cell migration and invasion. miR-31 targets include oncogenic kinases
      such as SRC, MET, NIK (MAP3K14) and the melanoma specific oncogene RAB27a.
      Furthermore, miR-31 overexpression resulted in down-regulation of EZH2 and a de
      repression of its target gene rap1GAP; increased expression of EZH2 was
      associated with melanoma progression and overall patient survival. Taken
      together, our study supports a tumor suppressor role for miR-31 in melanoma and
      identifies novel therapeutic targets.

PMID- 22948086
TI  - The prevalence of sensory deficits, functional limitations, and disability among
      older Southeast Asians in the United States.
AB  - OBJECTIVE: This study described the prevalence of and risk factors for sensory
      deficits, cognitive and physical functional limitations, and disability among
      older Southeast Asian refugees in the United States. METHODS: Data for the
      regression analyses were drawn from the 2003-2007 American Community Surveys. The
      sample included foreign-born persons aged 55 and older who were classified as
      Hmong, Cambodian, Laotian, and Vietnamese. RESULTS: Hmong, Cambodian, and Laotian
      persons were more likely to report a sensory deficit, functional limitation and
      disability than Vietnamese persons. Year of arrival, English language proficiency
      and education were important risk factors. Hmong and Cambodian groups had the
      most negative health profiles. DISCUSSION: Previous studies found that Vietnamese
      were the most health disadvantaged when compared to other Asian American groups
      and Whites. When compared to other refugee populations, the Vietnamese were
      actually the advantaged group. Our results indicated additional research on the
      disablement process among Southeast Asians is warranted.

PMID- 22948087
TI  - A combined multi-virulence-locus sequence typing and Staphylococcal Cassette
      Chromosome mec typing scheme possesses enhanced discriminatory power for
      genotyping MRSA.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains a major threat to
      human populations worldwide. Knowing the extent of MRSA genetic diversity within
      a healthcare facility may provide important insights into the epidemiology of
      this important pathogen. MRSA isolates recovered from nasal swabs of patients
      entering the Intensive Care Unit of the Penn State Milton S. Hershey Medical
      Center, USA, from 2008 to 2009 were genotyped using Staphylococcal Cassette
      Chromosome mec (SCCmec), multilocus sequence typing (MLST) and a newly developed
      multi-virulence-locus sequence typing (MVLST) scheme. Sequence data for seven
      housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi and yqiL) and six virulence
      genes (alt, essC, geh, hlgA, htrA and sdrC) were used for MLST and MVLST
      analyses, respectively. MLST identified 12 sequence types (STs) within the
      hospital isolates. One ST designated ST5 was the most common subtype (38.8%)
      followed by ST105 (22.4%) and ST8 (16.4%). In contrast, MVLST identified 29 STs
      (Virulence Types, VTs) from the same set of isolates, with VT6 (32.8%) being the
      predominant subtype followed by VT9 (8.9%) and VT2 (8.9%). Subsequent analysis of
      25 MRSA isolates associated with an outbreak at a Pennsylvania state prison
      revealed all isolates were VT2 and SCCmec type IVa. These results suggest that a
      combination of MVLST and SCCmec typing may clarify the epidemiology of MRSA.
      Additional research with a more diverse set of strains and correlation with
      conventional epidemiologic data are needed to validate this new subtyping
      strategy.

PMID- 22948088
TI  - Uniaxially aligned nanofibrous cylinders by electrospinning.
AB  - Aligned nanofibers have drawn increasing interest for applications in biomedical
      engineering, electronics, and energy storage systems owing to the unique
      physicochemical properties provided by their anisotropy and high surface-to
      volume ratio. Nevertheless, direct fabrication or assembly of aligned nanofibers
      into a 3-dimensional standalone construct with practically applicable dimensions
      presents an enormous challenge. We report a facile method to fabricate aligned
      nanofibrous cylinders, a widely used geometric form, by electrospinning aligned
      nanofibers across the gap between a pair of pin electrodes placed apart
      uniaxially. With this approach, cylindrical nanofibrous constructs of several
      millimeters in diameter and several centimeters in length can be readily
      produced. The versatility of the approach was demonstrated with several commonly
      used polymeric and ceramic materials, including polycaprolactone (PCL),
      chitosan/PCL, polyvinylidene fluoride, and titania. For a model application in
      tissue engineering, skeletal muscle cells were cultured on nanofibrous cylinders,
      which effectively produced highly aligned and densely populated myotubes along
      the nanofiber orientation, favorable for muscle tissue regeneration. With high
      structural integrity and stability, these can be directly integrated into devices
      or implanted in vivo as a standalone construct without the support of a
      substrate, thus increasing the portability, efficiency, and applicability of
      aligned nanofibers.

PMID- 22948089
TI  - Patients with Alzheimer disease have elevated intrathecal synthesis of antibodies
      against tau protein and heavy neurofilament.
AB  - The role of humoral immunity related to neuron- and disease-specific cytoskeletal
      proteins patients with Alzheimer disease (AD) is unknown. We measured antibodies
      against tau protein, light and heavy (NFH) neurofilaments using ELISA in 80
      paired serum and cerebrospinal fluid (CSF) samples from patients with AD, with
      other dementias (OD), with neuro-inflammatory diseases (IC) and 25 controls (NC).
      We estimated intrathecal synthesis according to the formula (CSF/serum anti
      neurocytoskeletal IgG)/(CSF/serum total IgG). AD patients had significantly
      higher intrathecal anti-tau and anti-NFH antibodies than the other groups. These
      innovative findings may hint at specific alterations in humoral anti
      neurocytoskeletal immunity and selectivity in AD, which could have diagnostic and
      immunotherapeutic implications.

PMID- 22948090
TI  - Characterization of natural killer cells in paired CSF and blood samples during
      neuroinflammation.
AB  - Natural killer (NK) cells from paired CSF and blood samples of patients with
      multiple sclerosis (MS), other neuroinflammatory diseases (IND), and non
      inflammatory neurological diseases (NIND) were characterized using flow
      cytometry. NK cell frequency in CSF was overall decreased compared to blood,
      particularly in MS patients. In contrast to blood NK cells, during
      neuroinflammation, CSF NK cells display an immature phenotype with bright
      expression of CD56 and CD27 and reduced CX3CR1 expression. Our findings suggest
      that, as for central memory T cells, CSF may represent an intermediary
      compartment for NK cell trafficking and differentiation before entering the CNS
      parenchyma.

PMID- 22948091
TI  - Telmisartan protects against cognitive decline via up-regulation of brain-derived
      neurotrophic factor/tropomyosin-related kinase B in hippocampus of hypertensive
      rats.
AB  - BACKGROUND AND PURPOSE: Cognitive decline may occur as a result of hypertension,
      and is dependent on the function of hippocampus. Brain-derived neurotrophic
      factor (BDNF) mediated by angiotensin II-induced oxidative stress protects
      against cell death in hippocampus. Angiotensin II receptor blocker (ARB),
      candesartan, activates BDNF in the hippocampus. Furthermore, peroxisome
      proliferator-activated receptor (PPAR)-gamma activation in the brain prevents
      brain damage. Telmisartan, a unique ARB with PPAR-gamma stimulating activity,
      protects against cognitive decline partly because of PPAR-gamma activation. The
      aim of the present study was to determine whether telmisartan protects against
      cognitive decline via up-regulation of BDNF and its receptor tropomyosin-related
      kinase B (TrkB) in the hippocampus of hypertensive rats, partly because of PPAR
      gamma activation. METHODS AND RESULTS: We divided stroke-prone spontaneously
      hypertensive rats (SHRSPs), as hypertensive and vascular dementia model rats,
      into five groups, telmisartan-treated (TLM), TLM+GW9662, a PPAR-gamma inhibitor, 
      treated (T+G), GW9662-treated (GW), TLM+ANA-12, a TrkB antagonist, -treated
      (T+A), and vehicle-treated SHRSPs (VEH). After the treatment for 28 days,
      systolic blood pressure did not change in all groups. However, BDNF expression in
      the hippocampus was significantly higher in TLM than in VEH to a greater extent
      than in T+G. Cognitive performance was significantly higher in TLM than in VEH to
      a greater extent than in T+G, and was not different between T+A, GW, and VEH.
      CONCLUSION: Telmisartan protects against cognitive decline via up-regulation of
      BDNF/TrkB in the hippocampus of SHRSPs, partly because of PPAR-gamma activation
      independent of blood pressure-lowering effect.

PMID- 22948092
TI  - Therapeutic effect of forest bathing on human hypertension in the elderly.
AB  - OBJECTIVE: To provide scientific evidence supporting the efficacy of forest
      bathing as a natural therapy for human hypertension. METHODS: Twenty-four elderly
      patients with essential hypertension were randomly divided into two groups of 12.
      One group was sent to a broad-leaved evergreen forest to experience a 7-day/7
      night trip, and the other was sent to a city area in Hangzhou for control. Blood
      pressure indicators, cardiovascular disease-related pathological factors
      including endothelin-1, homocysteine, renin, angiotensinogen, angiotensin II,
      angiotensin II type 1 receptor, angiotensin II type 2 receptor as well as
      inflammatory cytokines interleukin-6 and tumor necrosis factor alpha were
      detected. Meanwhile, profile of mood states (POMS) evaluation was used to assess
      the change of mood state of subjects. In addition, the air quality in the two
      experimental sites was monitored during the 7-day duration, simultaneously.
      RESULTS: The baselines of the indicators of the subjects were not significantly
      different. Little alteration in the detected indicators in the city group was
      observed after the experiment. While subjects exposed to the forest environment
      showed a significant reduction in blood pressure in comparison to that of the
      city group. The values for the bio-indicators in subjects exposed to the forest
      environment were also lower than those in the urban control group and the
      baseline levels of themselves. POMS evaluation showed that the scores in the
      negative subscales were lowered after exposure to the forest environment.
      Besides, the air quality in the forest environment was much better than that of
      the urban area evidenced by the quantitative detection of negative ions and PM10
      (particulate matter < 10 MUm in aerodynamic diameter). CONCLUSION: Our results
      provided direct evidence that forest bathing has therapeutic effects on human
      hypertension and induces inhibition of the renin-angiotensin system and
      inflammation, and thus inspiring its preventive efficacy against cardiovascular
      disorders.

PMID- 22948093
TI  - Botulinum toxin A for the treatment of keloids.
AB  - INTRODUCTION: Keloids are the result of excessive scar tissue formation. Besides
      their poor aesthetic appearance, keloids can be associated with severe clinical
      symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic
      approaches remain clinically unsatisfactory. Recently, injections with botulinum
      toxin A (BTA) were proposed for the treatment of established keloids in a
      clinical trial. In this study, we aimed to verify the effects of intralesional
      BTA for the treatment of therapy-resistant keloids using objective measurements.
      In addition, the underlying molecular mechanisms were investigated using cultured
      keloid-derived fibroblasts. MATERIALS AND METHODS: Four patients received BTA
      (doses varying from 70 to 140 Speywood units per session) injected directly into
      their keloids every 2 months for up to 6 months. Differences in height and volume
      were evaluated clinically and measured with a 3-D optical profiling system.
      Keloid-derived fibroblasts were treated with different concentrations of BTA, and
      expression of collagen (COL)1A1, COL1A2, COL3A1, TGF-beta1, TGF-beta2, TGF-beta3,
      fibronectin-1, laminin-beta2, and alpha-SMA was determined by real-time
      quantitative PCR. MTT and BrdU assays were used to analyze the effects of BTA on
      fibroblast proliferation and metabolism. RESULTS: Intralesional administration of
      BTA did not result in regression of keloid tissue. No differences in expression
      of ECM markers, collagen synthesis, or TGF-beta could be observed after BTA
      treatment of keloid fibroblasts. In addition, cell proliferation and metabolism
      of keloid fibroblasts was not affected by BTA treatment. CONCLUSION: The
      suggested clinical efficiency of intralesional BTA for the therapy of existent
      keloids could not be confirmed in this study. Based on our data, the potential
      mechanisms of action of BTA on keloid-derived fibroblasts remain unclear.

PMID- 22948094
TI  - Can healthy lifestyle modify risk factors for dementia? Findings from a pilot
      community-based survey in Chennai (India) and Newcastle (UK).
AB  - BACKGROUND: Currently there are no effective treatments available for dementia.
      Attention has turned to defining preventive strategies and identifying modifying
      effects of lifestyle, including physical activity, diet, alcohol intake and
      smoking, in reducing cognitive decline and overt memory problems in the elderly.
      METHODS: In this study, we addressed the modifying aspects of various components
      of lifestyle in two ageing samples and explored the possible effects that
      exercise, diet and spiritual and religious beliefs have upon physical and mental
      health. A total of 251 subjects (128 in Chennai, India, and 123 in Newcastle, UK)
      filled in a questionnaire regarding their lifestyle habits. Data were analysed
      with chi2 analysis. RESULTS: Our findings highlight that spiritual and religious
      beliefs promoted good physical and mental health and were negatively associated
      with risk factors for dementia, such as high blood pressure, high cholesterol
      level and diabetes. Lifelong diet and physical activity also contributed to
      better overall well-being in both samples. CONCLUSIONS: Our study suggests
      substantial lifestyle variations between two urban populations in Chennai, India,
      and Newcastle-upon-Tyne, UK. Further detailed work is required to identify the
      lifestyle components that have the greatest impact on modifying the known risk
      factors for dementia.

PMID- 22948095
TI  - Enantioselective organocatalytic domino synthesis of tetrahydropyridin-2-ols.
AB  - The asymmetric synthesis of tetrahydropyridin-2-ols from enals and enaminones is
      described. The organocatalytic domino reaction involves a Michael addition
      hemiaminalization sequence using the Jorgensen-Hayashi catalyst. Dehydration or
      oxidation leads to the corresponding 1,4-dihydro-pyridines or 3,4-dihydropyridin
      2-ones in a one-pot fashion.

PMID- 22948096
TI  - Microsatellite loci over a thirty-three year period for a malaria parasite
      (Plasmodium mexicanum): bottleneck in effective population size and effect on
      allele frequencies.
AB  - Changes in population allele frequencies may be driven by several forces,
      including selection and drift, and are revealed only by sampling over many
      generations. Such studies, however, are rare for protist parasites.
      Microsatellite allele frequencies for 4 loci were followed in a population of
      Plasmodium mexicanum, a malaria parasite of lizards in California USA at 1 site
      from 1978 to 2010. Rapid turnover of the lizards indicates the parasite was
      studied for a minimum of 33 transmission cycles and possibly twice that number.
      Sample sizes ranged from 841 to 956 scored parasite clones per locus. DNA was
      extracted from frozen dried blood and blood removed from stained blood smears
      from the earliest years, and a verification study demonstrated DNA from the blood
      smears provided valid genetic data. Parasite prevalence and effective population
      size (Ne) dropped after 2000, remaining lower for the next decade. For 2 loci,
      allele frequencies appeared stable for the first 2 decades of the study, but
      changed more rapidly after the decline in prevalence. Allele frequencies changed
      more gradually for the other 2 loci. Genetic drift could account for changes in
      allele frequencies, especially after the drop in prevalence and Ne, but the force
      of selection could also have driven the observed patterns.

PMID- 22948097
TI  - Are aging biomarkers clinically relevant in oncogeriatrics?
AB  - Immunosenescence and inflammaging have been depicted for long as age-related
      heterogeneous blood phenotypic changes ("immunoaging"). Some of them can be
      reproduced in animal models either by accelerating telomere shortening or by
      forcing DNA damage response. According to these models, "immunoaging" is the
      consequence of replicative senescence of hematopoietic stem cells. This
      increasing knowledge may impact oncogeriatrics in the future since (1) an
      increasing evidence links hematopoietic and cancer stem cells regulations; (2)
      immunosenescence may be linked to cancer immunotolerance and the increasing rate
      of cancer incidence with age; (3) immunoaging has a major consequence during
      cancer treatment, since it explains increased hematological toxicities observed
      in the elderly and (4) it favors secondary cancers and mainly hemopathies. For
      all these reasons, aging biomarkers, among which are telomere length peripheral
      blood sampling but also analyses of telomere-linked proteins like shelterin
      complex or DNA-damage markers will probably be clinically relevant in the future.

PMID- 22948098
TI  - A dynamic plasmonic manipulation technique assisted by phase modulation of an
      incident optical vortex beam.
AB  - A novel phase modulation method for dynamic manipulation of surface plasmon
      polaritons (SPPs) with a phase engineered optical vortex (OV) beam illuminating
      on nanoslits is experimentally demonstrated. Because of the unique helical phase
      carried by an OV beam, dynamic control of SPP multiple focusing and standing wave
      generation is realized by changing the OV beam's topological charge constituent
      with the help of a liquid-crystal spatial light modulator. Measurement of SPP
      distributions with near-field scanning optical microscopy showed an excellent
      agreement with numerical predictions. The proposed phase modulation technique for
      manipulating SPPs features has seemingly dynamic and reconfigurable advantages,
      with profound potential for development of SPP coupling, routing, multiplexing
      and high-resolution imaging devices on plasmonic chips.

PMID- 22948099
TI  - Extracorporeal photochemotherapy as systemic monotherapy of severe, refractory
      atopic dermatitis: results from a prospective trial.
AB  - BACKGROUND: Previous work has indicated that extracorporeal photochemotherapy
      (ECP) may be a safe and effective treatment in patients with severe atopic
      dermatitis. METHODS: We performed a prospective study to investigate the effect
      of a defined 20-week ECP protocol in patients with severe, refractory atopic
      dermatitis. The patient inclusion criteria included (i) disease duration of at
      least 1 year, (ii) SCORAD > 45, and (iii) resistance to first-line therapy,
      including topical steroids, topical calcineurin inhibitors, and one form of
      phototherapy (UVA, UVB, or PUVA) or one second-line therapy, including systemic
      steroids or cyclosporine. Ten patients (4 women and 6 men; age range 29 to 61
      years) were enrolled and treated with two sessions of standard ECP in 2-week
      intervals for 12 weeks and 4-week intervals thereafter until week 20. The
      patients' clinical status and response was determined by SCORAD at baseline and
      every 2 weeks, and quality of life was assessed every 4 weeks using SKINDEX, SF
      36, and FACT scores. RESULTS: There was a statistically significant (p = 0.015)
      reduction of the mean SCORAD by 10.3 (95% CI, 2.5 to 18.0) from 64.8 at baseline
      to 54.5 (i.e., 15.9% reduction) at week 20. In a subset of patients (all of
      female sex), the relative reduction in SCORAD after ECP was more than 25% at week
      20. Improvement in quality of life measured by SKINDEX, SF-36, and FACT did not
      reach statistical significance. CONCLUSIONS: We detected a small but significant
      therapeutic effect of ECP in patients with severe, refractory atopic dermatitis.

PMID- 22948100
TI  - Editorial.

PMID- 22948101
TI  - Understanding and reducing the risk of supply chain disruptions.
AB  - Natural disasters can wreck havoc on business operations. When civil unrest swept
      the UK in August 2011, the effect on business was stark, losing the retail sector
      L300m in unexpected costs and lost revenues. On the other side of the world, the
      natural disaster that hit Japan in early 2011 is estimated to have run up costs
      in the region of L189bn in repairs. Beyond this, the earthquake and its aftermath
      shattered supply chains, with technology companies expecting delays of up to six
      months before business could resume fully. It is impossible to predict incidents
      like these, but businesses can help mitigate disruption in the supply chain by
      undertaking business continuity management (BCM). A flexible supply chain is
      essential when it comes to BCM - whether it means being able to cope with
      altering transport routes at short notice, or finding or replacing a supplier at
      the last minute. Understanding the supply chain is critical when responding to
      major impacts that affect supply chains in multiple points - like IT system
      failures and country-wide fuel strikes. Businesses should carry out detailed
      business impact assessments and risk assessments right across the end-to-end
      supply chain and not just at key single points of failure. It is an intensive
      process that needs dedicated resources and ownership at the highest level.
      Recognising this, DHL has designed a 10-step process, which it has implemented
      across its global supply chain business. This paper provides an overview of what
      a supply chain really looks like, what can cause disruptions and how far up/down
      the supply chain companies need to go with their BCM planning.

PMID- 22948102
TI  - How effective incident management retains market share.
AB  - This paper discusses the need for business continuity practitioners to make
      incident management a focal element of their programme. Particularly during the
      first few minutes and hours of a business disruption, an established incident
      management methodology is not only key to achieving a successful, coordinated
      recovery, but it can play an even more important role in maintaining customer
      confidence following a disruption or crisis.

PMID- 22948103
TI  - Homeland security in the USA: past, present, and future.
AB  - This paper examines the evolving and dynamic field of homeland security in the
      USA. Included in this analysis is the evolution of the creation of the Department
      of Homeland Security, an overview of the National Warning System, a summary of
      citizen support groups, and how the field of homeland security has had an impact
      on the location and architecture of public buildings and facilities. Also
      included are website directories of citizen support groups and federal agencies
      related to the field of homeland security.

PMID- 22948104
TI  - Developing emergency exercises for hazardous material transportation: process,
      documents and templates.
AB  - Multi-agency emergency exercises establish and reinforce relationships, and bring
      people from different areas together to work as a team, realise clear goals,
      understand roles and responsibilities, and get to know and respect each agency's
      strengths and weaknesses. However, despite the long-held belief in and respect
      for exercises in their provision of benefits to the individual and the
      organisation, there is little evidence of a consistent and clear process for
      exercise design, especially identifying the documents that may need to be
      completed to ensure efficient exercise preparation and performance. This paper
      reports the results of a project undertaken on behalf of the organisations that
      form the radioactive material transportation mutual-aid agreement, RADSAFE, to
      develop a standardised process to design emergency exercises. Three stages, from
      identifying the requirement for an exercise (Stage I), through to obtaining
      approval for operational orders (Stage II), then conducting a management review
      as part of the continuous improvement cycle (Stage III), were developed. Although
      designed for radioactive material transportation events, it is suggested that
      many of the factors within these three stages can be generalised for the design
      of exercises in other high-hazard industries.

PMID- 22948105
TI  - Is preparedness for CBRN incidents important to general practitioners in East
      London?
AB  - General practitioners (GPs) have an important role in public health response to
      CBRN incidents, including disseminating information to worried patients and
      undertaking risk assessments of patients. The authors undertook the first known
      UK survey of GPs' CBRN preparedness to assess knowledge and attitudes towards
      CBRN preparedness among GPs in East London, in the area of the Olympic Park. A
      questionnaire was developed, focusing on GPs' self-preparedness for, and
      perceived roles in CBRN incidents, and GPs' access to resources and policies for
      dealing with such incidents. Of 157 GPs, 56 responded, although some responded
      collectively for their practice. The majority of respondents recognised roles for
      themselves in CBRN incidents, including recognition of illness, supporting
      decontamination, and appropriate reporting. However, 79 per cent of GPs also felt
      unprepared for such incidents. The most popular topic for training to address
      this was clinical presentation of CBRN exposures. Most practices had no policy
      for dealing with suspect packages and white powder incidents. Since this survey,
      guidance and training has been made available to local GPs. As the UK will host
      more events like the 2012 Olympics, preparedness for GPs will continue to be an
      important consideration in the UK.

PMID- 22948106
TI  - Understanding your supply chain to reduce the risk of supply chain disruption.
AB  - Supply chains are at the heart of the way in which organisations operate and
      compete today; they also play a critical role in overall organisation
      performance. In the context of increasingly complex and global supply chains, the
      actions taken to drive down costs are likely to drive risk into the supply chain.
      The frequency of supply chain disruptions is high and this paper offers practical
      advice to help reduce the frequency and cost associated with these. There is
      advice to help with the understanding of how to identify critical suppliers. The
      reader is guided through comprehensive risk assessment and mitigation approaches
      and a selection of practical risk solutions and tools that you can use is
      described. There is a section on the 'dos and don'ts' relating to supplier due
      diligence. For those organisations facing the challenge of drawing up a business
      case relating to investment in improving supply chain resiliency, there is also a
      section outlining some of the business benefits of improving supply chain
      resiliency.

PMID- 22948107
TI  - Creating a process for incorporating epidemiological modelling into outbreak
      management decisions.
AB  - Modern computational models of infectious diseases greatly enhance our ability to
      understand new infectious threats and assess the effects of different
      interventions. The recently-released CDC Framework for Preventing Infectious
      Diseases calls for increased use of predictive modelling of epidemic emergence
      for public health preparedness. Currently, the utility of these technologies in
      preparedness and response to outbreaks is limited by gaps between modelling
      output and information requirements for incident management. The authors propose
      an operational structure that will facilitate integration of modelling
      capabilities into action planning for outbreak management, using the Incident
      Command System (ICS) and Synchronization Matrix framework. It is designed to be
      adaptable and scalable for use by state and local planners under the National
      Response Framework (NRF) and Emergency Support Function #8 (ESF-8). Specific
      epidemiological modelling requirements are described, and integrated with the
      core processes for public health emergency decision support. These methods can be
      used in checklist format to align prospective or real-time modelling output with
      anticipated decision points, and guide strategic situational assessments at the
      community level. It is anticipated that formalising these processes will
      facilitate translation of the CDC's policy guidance from theory to practice
      during public health emergencies involving infectious outbreaks.

PMID- 22948108
TI  - The Arabic culture of Jordan and its impacts on a wider Jordanian adoption of
      business continuity management.
AB  - Culture is important to individuals and societies, as well as organisations.
      Failing to address cultural aspects will hinder the wider adoption and
      development of business continuity management (BCM) and will subsequently
      increase the vulnerabilities of organisations to crises, disasters and business
      interruptions. Three main issues are discussed in this paper. The first is the
      background to culture and the characteristics of the Jordanian culture. Secondly,
      the influence of the Arab culture on the wider adoption and development of BCM in
      Jordan is considered. Thirdly, the paper looks at potential factors that underpin
      the role of culture in the BCM process in Jordan. These issues are significant,
      as they represent the characteristics and influence of the Arab culture. This
      paper contributes to the understanding of the significance of culture in the
      adoption and development of BCM for organisations operating in Jordan and in the
      Arab world more generally. It also highlights current cultural changes and trends
      taking place in the Arab world in a time of huge political instability in the
      Middle East and Arab countries.

PMID- 22948109
TI  - Specific IgG4 production during house dust mite immunotherapy among age, gender
      and allergic disease populations.
AB  - BACKGROUND: Specific IgG4 induced by allergen-specific immunotherapy (SIT) is an
      immunological marker related to the appearance of clinical tolerance. But
      specific IgG4 levels in different age, gender and allergic disease populations
      have not been fully investigated. METHODS: This study involved 226 children and
      109 adults with allergic rhinitis and/or asthma receiving a 156-week course of
      Dermatophagoides pteronyssinus (Der p) subcutaneous SIT. Symptom and medication
      scores, forced expiratory volume after 1 s (FEV(1)) and Der p-specific IgG4
      levels at weeks 0, 5, 10, 25, 52, 104 and 156 were analyzed. RESULTS: Rhinitis
      symptom and medication scores and FEV(1) % predicted in children showed
      significantly greater improvement than in adults at week 104 and 156 (p < 0.05).
      Levels of Der p-specific IgG4 showed a significant increase after 10 weeks of
      subcutaneous SIT (p < 0.0001) and continued to increase during the 156-week SIT
      period. Before SIT, the initial Der p-specific IgG4 level was higher in children
      than adults (p = 0.0004). The increase ratio of Der p-specific IgG4 was higher in
      children than adults at 52 weeks (p < 0.001) and 104 weeks (p = 0.0156) of SIT,
      and was higher in rhinitis compared to asthma patients at 156 weeks of SIT (p =
      0.0244). There was no difference between males and females at any time points.
      CONCLUSION: Children are more responsive to SIT, demonstrating clinical and
      FEV(1) improvement and producing higher levels of allergen-specific IgG4 during a
      shorter SIT period compared to adults. Rhinitis patients show a higher increase
      in specific IgG4 compared to patients with asthma symptoms. The increase of Der p
      specific IgG4 reflects a specific response of the immune system towards the SIT
      vaccine being administrated.

PMID- 22948110
TI  - Sexual medicine: Let's talk about sex...

PMID- 22948111
TI  - Roughness of glancing angle deposited titanium thin films: an experimental and
      computational study.
AB  - The characterization of roughness at the nanoscale by the means of atomic force
      microscopy (AFM) was performed on high aspect ratio glancing angle deposited
      titanium thin films. With the use of scanning electron microscopy as well as x
      ray photoelectron spectroscopy, it was shown that the AFM measurements gave rise
      to incorrect roughness values for the films consisting of the highest aspect
      ratio structures. By correcting for this experimental artefact, the difference
      between the saturated roughness value of a film grown with conventional physical
      vapour deposition and films grown with a glancing angle of deposition was shown
      to behave as a power law function of the deposition angle, with a saturated
      roughness exponent of kappa = 7.1 +/- 0.2. This power law scaling was confirmed
      by three-dimensional molecular dynamics simulations of glancing angle deposition,
      where the saturated roughness exponent was calculated to kappa = 6.7 +/- 0.4.

PMID- 22948113
TI  - Subpleural versus deep lung biopsies obtained during pleuroscopy for histological
      examination: an experimental animal study.
AB  - BACKGROUND: Lung biopsies obtained during medical pleuroscopy using coagulating
      forceps could represent a cost-effective alternative to surgical lung biopsies in
      patients with diffuse parenchymal lung diseases (DPLD). However, it is not clear
      whether these patients should undergo deeplung biopsies rather than more
      superficial subpleural lung biopsies. OBJECTIVES: The aim of this experimental
      animal study was to compare gross and microscopic features of deep and subpleural
      pleuroscopic lung biopsy samples. METHODS: Six male sheep (median weight 40 kg)
      underwent lung biopsies via pleuroscopy under general anesthesia. The following
      parameters were studied: weight, size, quality of the parenchyma and visceral
      pleura, parenchymal vessels and bronchial tissue. RESULTS: The mean number of
      biopsies taken per animal was 4.5 +/- 1.22 and 4.83 +/- 1.33 (p = 0.36) for deep
      and subpleural biopsies, respectively. The mean size of deep and subpleural
      biopsies was 1.758 +/- 0.478 and 1.283 +/- 0.851 cm(2), respectively (p =
      0.0006). The mean weight of deep biopsies and subpleural biopsies was 0.156 +/-
      0.092 and 0.145 +/- 0.047 mg, respectively (p = 0.83). No statistically
      significant difference was found between subpleural and deep biopsies regarding
      the mean quality scores of parenchyma-pleura (p = 0.36), vessels (p = 0.36), or
      bronchial tissue (p = 0.20). CONCLUSION: Both subpleural biopsies obtained during
      pleuroscopy and deep lung biopsy specimens obtained by electrocautery in animal
      subjects provided satisfactory material for histologic examination. Therefore, in
      DPLD, where the subpleural layers are involved, subpleural biopsies obtained
      during pleuroscopy might be sufficient for establishing an accurate diagnosis.

PMID- 22948114
TI  - Bipolar charge storage characteristics in copper and cobalt co-doped zinc oxide
      (ZnO) thin film.
AB  - The bipolar charge phenomenon in Cu and Co co-doped zinc oxide (ZnO) film samples
      has been studied using scanning probe microscopy (SPM) techniques. Those ZnO
      samples are made using a pulsed laser deposition (PLD) technique. It is found
      that the addition of Cu and Co dopants suppresses the electron density in ZnO and
      causes a significant change in the work function (Fermi level) value of the ZnO
      film; this results in the ohmic nature of the contact between the electrode
      (probe tip) and codoped sample, whereas this contact exhibits a Schottky nature
      in the undoped and single-element-doped samples. These results are verified by
      Kelvin probe force microscopy (KPFM) and ultraviolet photoelectron spectroscopy
      (UPS) measurements. It is also found that the co-doping (Cu and Co) can stabilize
      the bipolar charge, whereas Cu doping only stabilizes the positive charge in ZnO
      thin films.

PMID- 22948112
TI  - Neuropilins are multifunctional coreceptors involved in tumor initiation, growth,
      metastasis and immunity.
AB  - The neuropilins (Nrps) are multifunctional proteins involved in development,
      immunity and cancer. Neuropilin-1 (Nrp1), or its homologue neuropilin-2 (Nrp2),
      are coreceptors that enhance responses to several growth factors (GFs) and other
      mediators. Nrps are coreceptors for the class 3 semaphorins (SEMA3), involved in
      axonal guidance, and several members of the vascular endothelial growth factor
      (VEGF) family. However, recent findings reveal they have a much broader spectrum
      of activity. They bind transforming growth factor beta1 (TGF-beta1) and its
      receptors, hepatocyte growth factor (HGF) and its receptor (cMet), platelet
      derived growth factor (PDGF) and its receptors, fibroblast growth factors (FGFs),
      and integrins. Nrps also promote Hedgehog signaling. These ligands and pathways
      are all relevant to angiogenesis and wound healing. In the immune system, the
      Nrps are expressed primarily by dendritic cells (DCs) and regulatory T cells
      (Tregs), and exert mainly inhibitory effects. In cancer, Nrps have been linked to
      a poor prognosis, which is consistent with their numerous interactions with
      ligands and receptors that promote tumor progression. We hypothesize that Nrps
      boost responses by capturing ligands, regulating GF receptor expression,
      endocytosis and recycling, and possibly also by signaling independently.
      Importantly, they promote epithelial-mesenchymal transition (EMT), and the
      survival of cancer stem cells. The recent finding that Nrps bind and internalize
      cell-penetrating peptides (CPPs) with arginine/lysine-rich C-terminal motifs (C
      end rule; e.g., RXXR) is of interest. These CPPs can be coupled to large drugs
      for cancer therapy. Almost all studies have been preclinical, but findings
      suggest Nrps are excellent targets for anti-cancer drug development.

PMID- 22948115
TI  - Setons in the treatment of anal fistula: review of variations in materials and
      techniques.
AB  - AIM: Anorectal fistulas have been a common surgical problem since ancient times.
      Age-old seton techniques are still practiced successfully in the treatment of
      complex anal fistulas. Many variations in materials and techniques are described
      in the literature. The selection of a seton type and technique depends on
      personal preferences. Our aim was to put together all the available variations in
      materials and techniques for seton treatment. This comprehensive review will help
      the surgeon to become more familiar with the various options available with
      regard to materials and techniques. METHODS: A review of the literature using
      Medline was done using the Key Words 'anal fistula' and 'seton'. All articles
      published in English were reviewed. The articles which had variations in
      materials and techniques for seton treatment were studied. RESULTS: Various
      aspects of variations in materials, insertion techniques, maintenance of tension,
      mechanisms of action, drainage techniques and changing the seton have been
      elaborated in detail. CONCLUSIONS: Throughout this paper we present the various
      available variations in setons with regard to materials, placement and
      maintenance techniques. This study will help clinicians in choosing a new seton
      variation or modifying their current method of treatment with setons.

PMID- 22948116
TI  - Clinicopathologic features and treatment response in nephrotic IgA nephropathy
      with minimal change disease.
AB  - OBJECTIVE: To analyze the clinicopathological features and therapeutic response
      of nephrotic IgA nephropathy (IgAN) patients with minimal-change disease (MCD).
      METHODS: 62 nephrotic IgAN patients were enrolled between January 2002 and
      December 2008, and divided into two groups including Group A: patients with MCD
      like pathological features, and Group B with non-MCD pathologic pattern. The
      clinicopathological features, treatments, and responses were then analyzed.
      RESULTS: 13 (21.0%) patients exhibited MCD-like pathological changes. Patients in
      Group A presented more prominent proteinuria, hypoalbuminemia but higher
      hemoglobin and no incidence of renal insufficiency compared to Group B (p <
      0.05). 62 patients were treated with corticosteroid, and the complete remission
      rate in Group A is higher than that in Group B (84.6% vs. 34.7%, p = 0.008), but
      the relapse rate is much higher in Group A (53.8% vs. 20.4%, p = 0.03). 21
      patients were treated combining with immunosuppressant due to unresponsiveness or
      relapse, which yielded a high re-remission rate in Group A (100%). After follow
      up of 53.9 +/- 26.9 months, the 5-year renal survival rate is higher in Group A
      (100%) than that in Group B (84.7%), but no significant difference was observed
      (p = 0.24). CONCLUSIONS: MCD-like pathological changes exist in quite a few
      nephrotic IgAN patients. These IgAN patients responded well to corticosteroid
      monotherapy but had a higher rate of relapse. Though manifesting with severe
      nephrotic symptoms, they tended to have a favorable clinical outcome probably due
      to the minimal pathological changes. Nevertheless, larger sample size and longer
      follow-up periods are needed for better understanding of the disease.

PMID- 22948117
TI  - Prevalence of chronic kidney disease in Jing adults in China: a village-based
      study.
AB  - AIM: Chronic kidney disease (CKD) is increasingly recognized as a predictor of
      end-stage renal and cardiovascular disease. There is no data on CKD prevalence in
      numerous minority communities of China such as the Guangxi Jing community. We
      determined CKD prevalence and related risk factors in Jing adults. METHODS: A
      stratified cluster random sampling method was used in this study comprising 757
      Jing adults. Questionnaires, physical examinations and laboratory tests including
      measurements of urinary albumin and hematuria, were performed. Estimated
      glomerular filtration rate (eGFR) was calculated using the improved Chinese
      population MDRD formula. CKD-related risk factors were also examined. RESULTS:
      After standardization for age and gender, the prevalence of albuminuria,
      haematuria and eGFR < 60 ml/min per 1.73 m2 was 12.5%, 3.8% and 0.4%,
      respectively Overall CKD prevalence was 15.3%, while the awareness rate was only
      11.6%. Females had a significantly higher (p < 0.05) prevalence of albuminuria,
      hematuria and eGFR < 60 ml/min compared to males. CKD prevalence tended to
      increase significantly (< 0.05) with increase in age. Using the standardized age
      and gender ratios, the prevalence of hypertension, diabetes, hyperlipidemia and
      hyperuricemia was 14.8%, 5.2%, 38% and 16.2%, respectively, with awareness of
      41.0%, 41.2%, 6.6% and 0.9%. Prevalence of overweight or obesity status and
      metabolic syndrome was 12.1% and 3.0%. Females showed a significantly higher
      prevalence of hyperuricemia and obesity or overweight status. CKD prevalence was
      also significantly higher in people with risk diseases. Regression analysis
      showed that age, gender, hypertension, high cholesterol and diabetes were CKD
      related risk factors, while culture (higher education level) was a protective
      factor. CONCLUSION: Jing adults showed a high CKD prevalence of 15.3%, with a low
      awareness rate of 11.6%. Older subjects and females were more susceptible with a
      high prevalence of hypertension, diabetes, hyperlipidemia, metabolic syndrome
      etc. being associated closely with CKD.

PMID- 22948118
TI  - ANCA-associated diseases and lung carcinomas: a five-case series.
AB  - Microscopic polyangiitis, granulomatosis with polyangiitis, Churg-Strauss
      syndrome and focal necrotizing glomerulonephritis are severe systemic
      vasculitides associated with circulating antineutrophil cytoplasmic antibodies
      (ANCA). Several studies reported that some malignancies can develop in these
      patients during follow-up, but few studies have considered the association and
      role of pre-existing cancers, at least in a fraction of patients. Herein, we
      report five patients with ANCA-associated diseases who had associated lung
      carcinomas or were diagnosed within 2 years after vasculitis onset. We discuss
      the putative role of tumor antigen in driving the auto-immune response. 

PMID- 22948119
TI  - Efficacy and safety of lanthanum carbonate in German patients on dialysis.
AB  - AIMS: To assess the treatment efficacy and tolerability of lanthanum carbonate
      (LC) in patients with end-stage renal disease (ESRD) and hyperphosphatemia under
      daily-practice conditions. PATIENTS AND METHODS: 698 patients on dialysis in 116
      outpatient dialysis centers in Germany were enrolled in this post-marketing
      surveillance study (mean treatment duration 6 months). LC treatment was compared
      to pretreatment (no or other phosphate binders) regarding laboratory parameters,
      adverse events and tablet burden. RESULTS: Compared to baseline, LC significantly
      reduced mean serum phosphate (SP), serum calcium, and calcium * phosphate product
      (p < 0.0001). In monotherapy with LC, mean tablet burden was decreased to 3.0
      tablets per day thus reducing the mean pre-study phosphatebinder tablet burden by
      nearly 50%. Adverse drug reactions associated with LC were reported in only 2.0%
      of the patients (n = 14). Overall, LC was considered safe and well tolerated.
      CONCLUSIONS: Under daily-practice conditions, LC at an average dose of 2,509 +/-
      936 mg/d was well tolerated and effective in adjusting and maintaining control of
      SP in patients previously being unsatisfactorily controlled on other phosphate
      binders. The daily tablet burden with a phosphate binder can be reduced to 3
      tablets of LC, particularly in patients on monotherapy. The lack of a comparison
      group should be considered in terms of careful interpretation of the study
      results.

PMID- 22948120
TI  - Patients with adult minimal change nephrotic syndrome treated with long-term
      cyclosporine did not experience a reduction in their eGFR.
AB  - BACKGROUND: The long-term efficacy and safety of cyclosporine (CyA) in the
      treatment of adult minimal change nephrotic syndrome (MCNS) was examined.
      METHODS: The medical record of 15 patients diagnosed with MCNS by renal biopsy
      and treated with CyA for at least 2 years were reviewed. RESULTS: The mean
      administration period of CyA was 78.3 months. The mean CyA dose for the induction
      period was 2.1 +/- 0.9 mg/kg and 1.7 +/- 1.0 mg/kg for the maintenance period.
      The mean dose of prednisolone used during the induction period was 20.3 mg and
      2.7 mg during the maintenance. The frequency of MCNS relapse was decreased to 0.5
      times/year in patients treated with CyA, compared to treatment without CyA (2.4
      times/y). Two cases of mild liver damage and 3 cases of elevated blood pressure
      were observed during the administration of CyA. These adverse effects improved
      after reducing the CyA dose or treatment with an antihypertensive agent. A
      decrease in the estimated glomerular filtraion rate (eGFR) was not associated
      with long-term CyA use. CONCLUSION: At our institution, patients who were treated
      for MCNS with CyA for at least 2 years experienced no deterioration in renal
      function.

PMID- 22948121
TI  - Renal lymphatic ligation aggravates renal dysfunction through induction of
      tubular epithelial cell apoptosis in mononephrectomized rats.
AB  - AIMS: To further explore the mechanisms of apoptosis in mononephrectomized rats
      with renal lymph circulation disorder. METHODS: Animals were divided into three
      groups: rats with left renal lymph ligation and right nephrectomy (KL), rats with
      only right nephrectomy (KN) and sham-operated rats (sham). 24-h proteinuria and
      serum creatinine level were monitored. Indexes of oxidative stress were measured.
      Renal apoptosis was examined. Further biochemical analysis was provided using
      real-time PCR, western blot and Elisa techniques. RESULTS: Our results showed
      that renal lymphatic ligation induced renal tubular epithelial cell apoptosis and
      aggravated renal dysfunction in mononephrectomized rats. In addition, renal
      lymphatic ligation increased the activities of caspase-3, caspase-8 and caspase
      9. Further investigation of mechanisms showed that renal lymphatic ligation up
      regulated Fas expression, increased the ratio of Bax/Bcl-2, and also increased
      the levels of reactive oxygen species (ROS), malondialdehyde (MDA) while reducing
      superoxide dismutase (SOD) activity. CONCLUSION: These results indicated that
      disturbance of renal lymphatic circulation might lead to tubular epithelial cell
      apoptosis through activation of intrinsic and extrinsic apoptotic pathways,
      suggestive of an essential role of renal lymphatic circulation in the maintenance
      of tubular integrity and function.

PMID- 22948122
TI  - Increased arterial stiffness in patients with nephrotic syndrome.
AB  - INTRODUCTION: Nephrotic syndrome (NS) and arterial stiffness (AS) have each been
      linked with increased risk for cardiovascular diseases. However, there is no data
      in the literature up-to-date on AS in adult patients with NS. Thus, in this
      study, we aimed to evaluate the potential associations between AS, volume and
      nutritional status in patients with NS in comparison to a healthy control group.
      METHODS: 34 adult patients with newly diagnosed but untreated NS and 34 healthy
      controls were studied. AS was assessed by carotid-femoral PWV (cf-PWV) and body
      composition, nutritional status by multifrequency bioelectric impedance analysis
      (BIA). RESULTS: Mean age was 44.6 +/- 18.7 years (18 - 72). Mean cf-PWV was 8.3
      +/- 2.5 m/s in patients with NS and 6.7 +/- 1.1 m/s in controls (p = 0.002) . In
      univariate analysis, cf-PWV and positively correlated with age, systolic blood
      pressure, mean arterial pressure (MAP), pulse pressure, body mass index, body fat
      ratio, waisthip ratio, creatinine, uric acid and negatively with creatinine
      clearance. In linear regression analysis, only age and MAP predicted arterial
      stiffness. Total body fluid, extracellular water (ECW), ECW/Height, ECW/body
      surface area and third space volumes were higher in patients with NS. CONCLUSION:
      Patients with NS have increased AS and are more hypervolemic compared to the
      healthy subjects.

PMID- 22948123
TI  - Validity and responsiveness of the Measure of Activity Performance of the Hand
      (MAP-Hand) in patients with hand osteoarthritis.
AB  - BACKGROUND: The Measure of Activity Performance of the Hand (MAP-Hand) is
      reliable and valid in patients with rheumatoid arthritis. OBJECTIVE: To assess
      the validity and responsiveness of the MAP-Hand in patients with hand
      osteoarthritis. METHODS: Patients were recruited from 2 rheumatology centres. The
      internal consistency of the MAP-Hand was assessed by Cronbach's alpha. Content
      validity was evaluated based on patient interviews. Construct validity and
      responsiveness were based on predefined hypotheses of correlation between the MAP
      Hand and concurrent measures. RESULTS: Ten men and 201 women, mean age 62.8 years
      (standard deviation (SD) 6.8) and disease duration 12.5 (SD 7.5) years were
      included. A Cronbach's alpha of 0.86 was determined. All 18 items in the MAP-Hand
      were described in the interviews. Sixty-seven percent of the correlation
      coefficients for baseline scores and 75% for change scores were in correspondence
      with the predefined hypotheses. A high correlation was found between the MAP-Hand
      and the Australian/Canadian Hand Osteoarthritis Index function score at baseline
      (rho = 0.76). A moderate correlation was found for change scores (rho = 0.52).
      CONCLUSION: The content of the MAP-Hand adequately reflects described activity
      limitations in patients with hand osteoarthritis. The results suggest that the
      MAP-Hand has adequate internal consistency and responsiveness. Before the MAP
      Hand is used in patients with hand osteoarthritis, evaluations of reliability and
      further construct validity are warranted.

PMID- 22948124
TI  - Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3-PBX1 fusion in an adult
      male with Down Syndrome.

PMID- 22948125
TI  - Decreased levels of Ca2+-calmodulin-dependent protein kinase IV in the testis as
      a contributing factor to reduced fertility in male Crybb2-/- mice.
AB  - betaB2-crystallin (Crybb2), a member of the betagamma-crystallin superfamily, in
      conjunction with alpha-crystallin, constitute the major proteins of the mammalian
      eye lens. Crybb2 is also expressed outside the lens, and certain related
      functions in these tissues have been reported. In the present study, in order to
      define the physiological role of Crybb2, we generated mice with a targeted
      deletion of the Crybb2 gene. Surprisingly, fertility was markedly reduced in male
      homozygous knockout mice compared to wild-type (WT) mice. Further experiments
      were performed to explore the underlying mechanism of subfertility in male Crybb2
      /- mice. Our results showed that Crybb2 was mainly expressed in the spermatogonia
      from the testes of mice with the WT C57BL/C genetic background. The testes of 4
      week-old Crybb2-/- mice were significantly hyperplastic, and no significant
      difference was found within 3 weeks postpartum. Additionally, there was a marked
      increase in the proliferation and apoptosis of germ cells, and the biological
      defects of these cells correlated with the decreased Bcl-2 levels, which
      correlated with the reduction of Ca2+-calmodulin-dependent protein kinase IV
      (CaMKIV) in the testis. These results suggest that the reduced fertility of
      Crybb2-/- male mice may result from the disordered proliferation and apoptosis of
      germ cells in the testis, possibly due to reduced CaMKIV from the loss of Crybb2.

PMID- 22948126
TI  - Can a screening questionnaire accurately identify mild Parkinsonian signs?
AB  - BACKGROUND: Mild parkinsonian signs (MPS) are early features that, when present,
      increase the risk of neurodegenerative disease and mortality. Current methods to
      identify MPS are limited to neurological examination. Our objective was to assess
      the ability of a 9-item Parkinson's Disease Screening Questionnaire (PDSQ), which
      has high sensitivity in the detection of overt Parkinson's disease (PD), to
      detect MPS. METHODS: Measures including the PDSQ, Unified Parkinson's Disease
      Rating Scale and University of Pennsylvania Smell Identification Test were
      administered to 267 participants without neurodegenerative disease. Two published
      definitions of MPS were used to classify cases. RESULTS: PDSQ scores were higher
      for cases compared to controls (p < 0.001 for the first case definition and 0.07
      for the second). However, the questionnaire had low sensitivity (47 and 59%) and
      specificity (62 and 63%) in the detection of MPS. Adding factors such as age,
      gender and smell test score to the questionnaire in a predictive model only
      marginally improved the test characteristics. CONCLUSION: The results show the
      screening questionnaire does not accurately identify MPS. More accurate tests are
      needed to improve the detection of this early syndrome which can lead to motor
      disability, neurodegenerative disease and mortality.

PMID- 22948127
TI  - A community based epidemiological study of epilepsy in Assiut Governorate/Egypt.
AB  - BACKGROUND: The aim of the study was to estimate the prevalence of different
      types of epilepsy and their possible risk factors in the region of the Assiut
      Governorate/Egypt. MATERIAL AND METHODS: A community based study with random
      sampling of 7 districts, involving 6498 inhabitants. Out of this sample, 578
      dropped out leaving 3066 males (51.8%) and 2854 females (48.2%). There were 3660
      (61.8%) urban residents and 2260 (38.2%) from the rural community. Patients were
      evaluated using a screening questionnaire for epilepsy, and then referred to the
      hospital to be re-evaluated by a qualified neurologist and with
      electroencephalography (EEG) and computed tomography of the brain (CT). RESULTS:
      Seventy-five cases were diagnosed with epilepsy giving an overall the crude
      lifetime prevalence rate (CPR) for epilepsy of 12.67/1000 (95% CI: 9.8-15.54).
      The active prevalence rate was 9.3/1000 and the incidence rate was 1.5/1000 (95%
      confidence interval: 0.53-2.51). Fifty-six cases (75%) had idiopathic epilepsy
      (CPR 9.5/1000). Symptomatic epilepsy was recorded in 19 (25%) cases (CPR
      3.2/1000). Generalized seizures were more common (CPR 6.75/1000) than partial
      seizures (CPR 2.5/1000). The prevalence rate of partial seizures evolving to
      secondary generalization was 0.84/1000 while simple partial and complex partial
      seizures had CPR 1.4/1000 and 0.34/1000, respectively. The CPR of mixed seizures
      was 0.17/1000. Epilepsy was slightly but not significantly more common among
      males than females (CPR of 14.4 and 10.9 per 1000 population, respectively). The
      CPR was higher in rural than urban populations (17.7/1000, with 95% CI 12.2-23.18
      and 9.56/1000, with 95% CI: 6.39-12.7, respectively) and in the illiterate group
      than the literate population (12.02/1000 and 9.94/1000, respectively). The
      highest prevalence rate was recorded in the early and late childhood period
      (69.78/100,000 and 43.78/100,000, respectively). Prenatal insults and infection
      represented major causes of symptomatic epilepsy. CONCLUSIONS: We found a high
      prevalence rate of epilepsy (comparable with that in other Arabic and European
      countries) in our community particularly among children and teenagers. Overall
      the prevalence was higher in the rural than in the urban population. A family
      history of epilepsy, prenatal insults, and infection represented major risk
      factors of symptomatic epilepsy.

PMID- 22948128
TI  - Expression of corticotropin releasing factor receptor type 1 (CRF1) in the human
      gastrointestinal tract and upregulation in the colonic mucosa in patients with
      ulcerative colitis.
AB  - Brain corticotropin-releasing factor (CRF) acting on CRF receptor type 1 (CRF(1))
      is a main signaling pathway in the stress response. CRF is also produced in a
      variety of peripheral sites and acts locally as a proinflammatory mediator. We
      investigated CRF(1) mRNA expression in the human gastrointestinal tract, and
      localized CRF(1) immunoreactive cells in the colonic mucosa of healthy subjects
      and patients with ulcerative colitis (UC). In 4 male healthy subjects (24-29
      years), CRF(1) transcript was detected by RT-PCR throughout the gastrointestinal
      tract with the highest levels in the ileum and rectum and the lowest level in the
      colon. Immunohistochemistry on whole thickness sigmoid colon sections showed that
      CRF(1) was localized in the lamina propria and epithelial cells and enteric
      neurons. In sigmoid colonic biopsies, immunohistochemically double-labeled cells
      with CRF(1) and CD163, a marker for macrophages, represent 79% of total CRF(1)
      immunoreactive (IR) cells in healthy subjects. In 10 UC patients, the total
      number of CRF(1) IR cells and CRF(1)/CD163 double-labeled macrophages was
      increased by 4.2 and 4.0 folds respectively compared to healthy subjects. These
      findings indicate that CRF(1) is distributed throughout the GI tract of healthy
      human subjects. The increase of CRF(1) IR cells prominently in macrophages of the
      sigmoid colonic mucosa of UC patients provides anatomical support for a role of
      CRF(1) signaling in modulating the immune-inflammatory process of UC.

PMID- 22948129
TI  - Interplay between crystal phase purity and radial growth in InP nanowires.
AB  - The interplay between crystal phase purity and radial growth in InP nanowires is
      investigated. By modifying the growth rate and V/III ratio, regions of high or
      low stacking fault density can be controllably introduced into wurtzite
      nanowires. It is found that regions with high stacking fault density encourage
      radial growth. Through careful choice of growth conditions pure wurtzite InP
      nanowires are then grown which exhibit narrow 4.2 K photoluminescence linewidths
      of 3.7 meV at 1.490 meV, and no evidence of emission related to stacking faults
      or zincblende insertions.

PMID- 22948130
TI  - Association between subjective feelings of distress, plasma cortisol, anxiety,
      and depression in pregnant women.
AB  - OBJECTIVE: Psychosocial stressors are consistently associated with antenatal
      anxiety and depression, while the impact of cortisol has proved inconsistent.
      Most studies have focused either on psychological or physiological stress
      indices. We investigated both subjective and endocrinologic indices of distress
      in the same subjects. STUDY DESIGN: We performed a cross-sectional study in late
      pregnancy in 79 women to investigate associations between the factors involved in
      anxiety and depression. Outcome measures were the Beck Depression Inventory
      (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale, a Likert
      like scale for fear of delivery, a structured interview to assess health and
      socioeconomic status, and fasting plasma cortisol levels measured in the morning.
      RESULTS: High BDI and STAI scores were associated with high levels of perceived
      stress and fear of delivery, but not with levels of plasma cortisol typical of
      the gestation phase. A multiple regression analysis revealed that subjective
      feelings of distress explained over 50% of the variation in BDI and STAI scores.
      Plasma cortisol was not a significant predictor of psychometric scores and did
      not show significant correlation with them in correlation analyses, and subjects
      with low and high cortisol levels showed similar psychometric scores. CONCLUSION:
      Antenatal depression and anxiety were significantly associated with subjective
      feelings of distress but not with increased cortisol. This finding may be
      explained by the blunted cortisol stress responses characteristic of pregnancy.
      The mechanisms mediating the effects of subjective distress remain obscure:
      likely candidates include monoamine neurotransmission, and/or stress-induced
      changes in glucocorticoid receptor expression or distribution.

PMID- 22948131
TI  - Independent effects of pregnancy induced hypertension on childhood development: a
      retrospective cohort study.
AB  - OBJECTIVE: To assess whether maternal hypertension in pregnancy was independently
      associated with additional support needs in children. STUDY DESIGN: Retrospective
      cohort study using linkage of birth records of all singleton deliveries occurring
      in primigravidae between 1995 and 2008 in Aberdeen Maternity and Neonatal
      Databank with the Support Needs System (SNS) dataset in Grampian. Crude and
      adjusted odds ratios with 95% confidence intervals of having a record in SNS in
      the presence of maternal pregnancy induced hypertension were calculated using
      logistic regression taking account of confounders such as preterm birth and low
      birth weight. RESULTS: After adjusting for confounding factors, neither pre
      eclampsia {Adj OR 0.80 (95% CI 0.60, 1.07)} nor gestational hypertension {Adj OR
      1.16 (95% CI 0.99, 1.36)} showed statistically significant associations with
      additional support needs. An association of pre-eclampsia with cerebral palsy
      seen on univariate analysis also disappeared on adjusting for confounders {Adj OR
      1.26 (95% CI 0.43, 3.68)}. Birth before 32 weeks gestation and birthweight below
      1500g were independently associated with additional support needs in children.
      CONCLUSIONS: While maternal hypertension was not found to be independently
      associated with special needs in children, very preterm birth and very low
      birthweight showed an association.

PMID- 22948132
TI  - Can dopamine agonist at a low dose reduce ovarian hyperstimulation syndrome in
      women at risk undergoing ICSI treatment cycles? A randomized controlled study.
AB  - OBJECTIVE: Dopamine agonists were proposed as a preventive strategy for severe
      ovarian. The aim of this randomized controlled study is to evaluate the role of
      dopamine agonist at lower doses (0.25mg) as a preventive strategy of severe
      hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment
      cycles. STUDY DESIGN: Two hundred women at risk to develop OHSS undergoing
      IVF/ICSI treatment cycle were included; the study group received 0.25mg of
      cabergoline for 8 days from the day of HCG administration versus no treatment for
      the prevention of OHSS. Reduction of the incidence OHSS was the primary outcome.
      RESULTS: The overall incidence of OHSS was significantly reduced, almost 50%, in
      cabergoline group in comparison with control group (RR: 0.5, 95% CI: 0.29-0.83),
      with absolute risk reduction following cabergoline administration 11% (ARR: 0.11,
      95% CI: 1.09-20.91). The corresponding number needed to treat (NNT) was 9.
      CONCLUSION: Prophylactic treatment with the dopamine agonist, cabergoline, at
      lower doses (0.25mg) reduces the incidence of OHSS in women at high risk
      undergoing IVF/ICSI treatment.

PMID- 22948133
TI  - Minimal cold knife conization height for high-grade cervical squamous
      intraepithelial lesion treatment.
AB  - OBJECTIVES: To assess the relationship between cold-knife conization specimen
      height, cervical intraepithelial neoplasia (CIN II/III) size and endocervical
      margin involvement by CIN II/II. STUDY DESIGN: A cross-sectional study was
      performed. Cold knife cone specimens with a diagnosis of CIN II/III were
      selected. Epidemiological data and pathology reports were obtained through a
      chart review. All samples from each cone specimen showing CIN II/III and the
      squamocolumnar junction were selected. Cone height (mean +/- standard deviation),
      intraepithelial lesion size, and size of endocervical surgical margins were
      measured. RESULTS: Four hundred and forty-seven samples were analyzed from 97
      cone specimens. Section size ranged from 3.4 to 29.7 mm, tumor size from 0.3 to
      17.5mm, and tumor distance from the endocervical margin, from 0.0 to 22.0mm. Age
      and parity were similar in the positive vs. negative margin groups (37.6 +/- 10.0
      years vs. 37.7 +/- 11.9 years respectively, p=0.952, and 2.2 +/- 1.7 births vs.
      2.6 +/- 1.9 births respectively, p=0.804), whereas cone height (22.4 +/- 6.9 mm
      vs. 17.1 +/- 5.6mm, p=0.013) and tumor size (6.12 +/- 3.25 mm vs. 10.6 +/- 4.45
      mm, p<0.001) were significantly different in negative vs. positive margin groups
      respectively. CONCLUSIONS: Use of cone height to identify the likelihood of
      negative margins enables better estimation of the risk-benefit ratio of greater
      risks of bleeding, stenosis, and obstetric complications (cervical incompetence)
      versus greater risks of residual and recurrent disease.

PMID- 22948134
TI  - Epidemiological perspectives on West Nile virus surveillance in wild birds in
      Great Britain.
AB  - West Nile virus (WNV) is a zoonotic arthropod-borne pathogen with continued
      geographical expansion in Europe. We present and evaluate data on the temporal,
      spatial and bird species focus of the WNV surveillance programme in dead wild
      birds in Great Britain (2002-2009). During this period all bird samples tested
      negative for WNV. Eighty-two per cent of the 2072 submissions occurred during the
      peak period of vector activity with 53% tested during April-July before human and
      equine infection would be expected. Samples were received from every county, but
      there was significant geographical clustering (nearest neighbour index=0.23,
      P<0.001). Over 240 species were represented, with surveillance more likely to
      detect WNV in resident bird species (92% of submissions) than migrants (8%).
      Evidence indicates that widespread avian mortality is not generally a reported
      feature of WNV in Europe and hence additional activities other than dead bird
      surveillance may maximize the ability to detect WNV circulation before the onset
      of human and equine infections.

PMID- 22948135
TI  - Quantitative SPECT/CT reconstruction for 177Lu and 177Lu/90Y targeted
      radionuclide therapies.
AB  - We investigated the quantitative accuracy of SPECT/CT imaging studies as would be
      performed before and after targeted radionuclide therapy (TRT) using phantom
      experiments with (i) (99m)Tc, (ii) 177Lu and (iii) 90Y/177Lu. While the
      experiment with (99m)Tc imitated a diagnostic scan, the experiments with 177Lu
      and 90Y/177Lu modeled post-therapy acquisitions. At the next stage, we
      reconstructed images from pre- and post-therapy patient studies. The data were
      first reconstructed using two methods with limited corrections for the physics
      effects. Then, to generate quantitatively accurate absolute activity
      distributions, we applied a hybrid (model-based and window-based) reconstruction
      strategy where some of the physics effects were accurately modeled while
      corrections for other effects were empirical and based on information obtained
      from the projection data. The accuracies of absolute activity recovered by the
      hybrid method from the six phantom experiments were very similar to each other
      and acceptable for potential use in TRT. When measured in identical regions of
      interest, the (99m)Tc 90activity was reconstructed with errors ranging between 
      3.3% and 2.9%, while the 177Lu activity was reconstructed from experiments with
      177Lu and Y/177Lu with errors ranging between -1.6% and 1.6%. The reconstruction
      algorithms with limited corrections led to larger and case-specific errors as
      might have been expected. From a clinical prospective, our results showed that
      physics-based reconstructions improved resolution of images corresponding to both
      diagnostic scans with (99m)Tc and post-therapy scans with 177Lu. Our analysis of
      patient study demonstrated that lack of corrections led to overestimation of
      activities in organs and tumor by 29-39% for the diagnostic scan with (99m)Tc and
      by 105-218% for post-therapy scan with 177Lu.

PMID- 22948136
TI  - Understanding discontinuation of oral adjuvant endocrine therapy by women with
      hormone receptor-positive invasive breast cancer nearly 4 years from diagnosis.
AB  - OBJECTIVE: The aim of this study was to investigate the extent of discontinuation
      of oral adjuvant endocrine therapy (OAET) in women nearly 4 years from the
      diagnosis of their first episode of invasive breast cancer and the reasons for
      such discontinuation. METHODS: We used a large, prospective cohort study of women
      who had been diagnosed with their first episode of invasive breast cancer between
      2004 and 2006, recruited through a state-based cancer registry. All participants
      completed an enrollment questionnaire (EQ) within 12 months of diagnosis and
      annual follow-up questionnaires (FQs) thereafter. The data in this report were
      obtained from the EQ and the first three FQs. RESULTS: A total of 1,370 women
      with hormone receptor-positive disease completed the EQ. At the completion of the
      third FQ nearly 4 years from diagnosis, 1,193 women remained in the study. Use of
      OAET peaked by 2 years postdiagnosis. At nearly 4 years from diagnosis, 18% of
      the 1,193 women remaining in the study were not taking OAET. Of these women, just
      more than half had ceased therapy mainly owing to a range of adverse effects,
      predominantly estrogen deficiency symptoms, but the remainder (8% of women
      remaining in the study) had never used OAET. CONCLUSIONS: Our study confirms that
      early discontinuation of OAET due to estrogen deficiency symptoms remains an
      important issue despite calls for strategies to address this problem. The number
      of women potentially suitable for OAET but not receiving it was almost as great
      as the number of those who have discontinued therapy.

PMID- 22948137
TI  - Frequency of FRAX risk factors in osteopenic postmenopausal women with and
      without history of fragility fracture.
AB  - OBJECTIVE: Fractures associated with bone fragility represent a major public
      health concern. Although the risk of bone fracture is higher among patients with
      osteoporosis, the number of fractures is usually higher among patients with
      osteopenia due to its higher prevalence. METHODS: This is an observational case
      series study that compares the frequencies of nonskeletal risk factors for
      osteoporotic fractures in osteopenic postmenopausal women with previous clinical
      fragility fractures (FFs) and osteopenic postmenopausal women without previous
      FF. Risk factors included in the FRAX algorithm and other selected risk factors,
      including asymptomatic vertebral fractures, were evaluated. RESULTS: A total of
      735 (50.3% with prior FF and 49.7% without prior FF) postmenopausal women were
      evaluated (median age, 60 y; mean bone mineral density [BMD] femoral neck T score
      of -1.67). The frequency of the following risk factors was significantly higher
      among women with FF-FRAX algorithm: age, use of corticosteroids, and BMD femoral
      neck T score; other factors: Hispanic ethnicity, falls during the last year, and
      BMD lumbar T score. In addition, the frequency of previously undetected
      asymptomatic vertebral fractures was four times higher among women with a history
      of FF. CONCLUSIONS: The results of the present study support the need to assess
      the presence of asymptomatic vertebral fractures and BMD T scores in osteopenic
      postmenopausal women. The risk evaluation of this subpopulation can be
      accomplished by using some of the risk factors included in the FRAX algorithm
      combined with other conventional risk factors.

PMID- 22948138
TI  - Implementation of fast-track protocols in open and laparoscopic sphincter
      preserving rectal cancer surgery: a multicenter, comparative, prospective, non
      randomized study.
AB  - BACKGROUND: Data on the role of laparoscopy within an enhanced recovery protocol
      for rectal cancer patients is rather limited. The aim of the study was to
      investigate the role of laparoscopy within a 'fast-track' protocol in patients
      who underwent sphincter-preserving surgery for rectal cancer. PATIENTS/METHODS:
      156 consecutive patients with low rectal cancer from three centers were assigned
      in four groups: the open fast track (OPEN-FT), the laparoscopic fast track (LAP
      FT), the open (OPEN), and the laparoscopic (LAP). The fast-track protocol was
      applied in one center and traditional care in the other two. All patients
      underwent sphincter-preserving surgery and were followed-up for 30 days. RESULTS:
      Overall morbidity was less in the fast-track groups (p = 0.007). On the other
      hand, no statistical significance could be identified in mortality, readmission
      or reoperations rates among the groups (p = 0.562, p = 0.896, p = 0.238). Fast
      track patients required significantly less intramuscular opioids for
      postoperative analgesia (p < 0.001). Primary (p < 0.001) and total hospital stays
      (p < 0.001) were significantly shorter in the fast-track groups. CONCLUSION: The
      implementation of a fast-track protocol is feasible and safe in low rectal cancer
      patients. Laparoscopy seems to be a basic element of such protocol as it further
      enhances recovery and reduces morbidity.

PMID- 22948139
TI  - Protein kinase PKR amplification of interferon beta induction occurs through
      initiation factor eIF-2alpha-mediated translational control.
AB  - The protein kinase PKR is activated by RNA with double-stranded (ds) structure
      and subsequently impairs translation through phosphorylation of protein synthesis
      initiation factor eIF-2alpha. PKR also mediates activation of signal transduction
      pathways leading to interferon beta (IFN-beta) gene induction following virus
      infection or RNA transfection. We previously demonstrated in measles virus
      infected cells that PKR is required for the maximal induction of IFN-beta gene
      expression by the interferon promoter stimulator gene 1 (IPS-1) adaptor-dependent
      cytosolic RNA sensor pathway. While both IPS-1 and PKR are important mediators of
      IFN-beta induction, with PKR contributing to an enhanced NF-kappaB activation,
      the mechanism by which PKR enhances NF-kappaB activity and amplifies IFN-beta
      induction is unresolved. Herein we tested the possibility that PKR could activate
      signal transduction pathways indirectly through translational control responses.
      Following transfection with synthetic or natural dsRNAs or infection with measles
      virus, we observed increased mRNA but decreased protein levels for the inhibitor
      of NF-kappaB signaling, IkappaB-alpha, that correlated with PKR activation and
      eIF-2alpha phosphorylation. Importantly, knockdown of PKR increased IkappaB-alpha
      protein levels and impaired IFN-beta induction. Additionally, inhibition of
      translation by cycloheximide treatment rescued IFN-beta induction following PKR
      knockdown but not IPS-1 knockdown. Mutation of eIF-2alpha to prevent
      phosphorylation also impaired IFN-beta induction in PKR-sufficient virus-infected
      cells. These results suggest that an eIF-2alpha-dependent translation inhibition
      mechanism is sufficient to explain the PKR-mediated amplification of IPS-1
      dependent IFN-beta induction by foreign RNA.

PMID- 22948140
TI  - Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in
      nerve cells confers resistance to amyloid beta and other toxins by decreasing
      mitochondrial respiration and reactive oxygen species production.
AB  - We previously demonstrated that nerve cell lines selected for resistance to
      amyloid beta (Abeta) peptide exhibit elevated aerobic glycolysis in part due to
      increased expression of pyruvate dehydrogenase kinase 1 (PDK1) and lactate
      dehydrogenase A (LDHA). Here, we show that overexpression of either PDK1 or LDHA
      in a rat CNS cell line (B12) confers resistance to Abeta and other neurotoxins.
      Treatment of Abeta-sensitive cells with various toxins resulted in mitochondrial
      hyperpolarization, immediately followed by rapid depolarization and cell death,
      events accompanied by increased production of cellular reactive oxygen species
      (ROS). In contrast, cells expressing either PDK1 or LDHA maintained a lower
      mitochondrial membrane potential and decreased ROS production with or without
      exposure to toxins. Additionally, PDK1- and LDHA-overexpressing cells exhibited
      decreased oxygen consumption but maintained levels of ATP under both normal
      culture conditions and following Abeta treatment. Interestingly, immunoblot
      analysis of wild type mouse primary cortical neurons treated with Abeta or
      cortical tissue extracts from 12-month-old APPswe/PS1dE9 transgenic mice showed
      decreased expression of LDHA and PDK1 when compared with controls. Additionally,
      post-mortem brain extracts from patients with Alzheimer disease exhibited a
      decrease in PDK1 expression compared with nondemented patients. Collectively,
      these findings indicate that key Warburg effect enzymes play a central role in
      mediating neuronal resistance to Alphabeta or other neurotoxins by decreasing
      mitochondrial activity and subsequent ROS production. Maintenance of PDK1 or LDHA
      expression in certain regions of the brain may explain why some individuals
      tolerate high levels of Abeta deposition without developing Alzheimer disease.

PMID- 22948141
TI  - An engineered disulfide bond reversibly traps the IgE-Fc3-4 in a closed,
      nonreceptor binding conformation.
AB  - IgE antibodies interact with the high affinity IgE Fc receptor, FcepsilonRI, and
      activate inflammatory pathways associated with the allergic response. The IgE-Fc
      region, comprising the C-terminal domains of the IgE heavy chain, binds
      FcepsilonRI and can adopt different conformations ranging from a closed form
      incompatible with receptor binding to an open, receptor-bound state. A number of
      intermediate states are also observed in different IgE-Fc crystal forms. To
      further explore this apparent IgE-Fc conformational flexibility and to
      potentially trap a closed, inactive state, we generated a series of disulfide
      bond mutants. Here we describe the structure and biochemical properties of an IgE
      Fc mutant that is trapped in the closed, non-receptor binding state via an
      engineered disulfide at residue 335 (Cys-335). Reduction of the disulfide at Cys
      335 restores the ability of IgE-Fc to bind to its high affinity receptor,
      FcepsilonRIalpha. The structure of the Cys-335 mutant shows that its conformation
      is within the range of previously observed, closed form IgE-Fc structures and
      that it retains the hydrophobic pocket found in the hinge region of the closed
      conformation. Locking the IgE-Fc into the closed state with the Cys-335 mutation
      does not affect binding of two other IgE-Fc ligands, omalizumab and DARPin E2_79,
      demonstrating selective blocking of the high affinity receptor binding.

PMID- 22948142
TI  - Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a
      plasma membrane H+ gradient.
AB  - Human NHA2, a newly discovered cation proton antiporter, is implicated in
      essential hypertension by gene linkage analysis. We show that NHA2 mediates
      phloretin-sensitive Na(+)-Li(+) counter-transport (SLC) activity, an established
      marker for hypertension. In contrast to bacteria and fungi where H(+) gradients
      drive uptake of metabolites, secondary transport at the plasma membrane of
      mammalian cells is coupled to the Na(+) electrochemical gradient. Our findings
      challenge this paradigm by showing coupling of NHA2 and V-type H(+)-ATPase at the
      plasma membrane of kidney-derived MDCK cells, resulting in a virtual Na(+) efflux
      pump. Thus, NHA2 functionally recapitulates an ancient shared evolutionary origin
      with bacterial NhaA. Although plasma membrane H(+) gradients have been observed
      in some specialized mammalian cells, the ubiquitous tissue distribution of NHA2
      suggests that H(+)-coupled transport is more widespread. The coexistence of Na(+)
      and H(+)-driven chemiosmotic circuits has implications for salt and pH regulation
      in the kidney.

PMID- 22948143
TI  - Demonstration of phosphoryl group transfer indicates that the ATP-binding
      cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator
      (CFTR) exhibits adenylate kinase activity.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane-spanning
      adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter. ABC
      transporters and other nuclear and cytoplasmic ABC proteins have ATPase activity
      that is coupled to their biological function. Recent studies with CFTR and two
      nonmembrane-bound ABC proteins, the DNA repair enzyme Rad50 and a structural
      maintenance of chromosome (SMC) protein, challenge the model that the function of
      all ABC proteins depends solely on their associated ATPase activity. Patch clamp
      studies indicated that in the presence of physiologically relevant concentrations
      of adenosine 5'-monophosphate (AMP), CFTR Cl(-) channel function is coupled to
      adenylate kinase activity (ATP+AMP <==> 2 ADP). Work with Rad50 and SMC showed
      that these enzymes catalyze both ATPase and adenylate kinase reactions. However,
      despite the supportive electrophysiological results with CFTR, there are no
      biochemical data demonstrating intrinsic adenylate kinase activity of a membrane
      bound ABC transporter. We developed a biochemical assay for adenylate kinase
      activity, in which the radioactive gamma-phosphate of a nucleotide triphosphate
      could transfer to a photoactivatable AMP analog. UV irradiation could then trap
      the (32)P on the adenylate kinase. With this assay, we discovered phosphoryl
      group transfer that labeled CFTR, thereby demonstrating its adenylate kinase
      activity. Our results also suggested that the interaction of nucleotide
      triphosphate with CFTR at ATP-binding site 2 is required for adenylate kinase
      activity. These biochemical data complement earlier biophysical studies of CFTR
      and indicate that the ABC transporter CFTR can function as an adenylate kinase.

PMID- 22948144
TI  - HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a
      ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can
      interact with HCN2.
AB  - A unique coupling between HCN1 and stereociliary tip-link protein protocadherin
      15 has been described for a teleost vestibular hair-cell model and mammalian
      organ of Corti (OC) (Ramakrishnan, N. A., Drescher, M. J., Barretto, R. L.,
      Beisel, K. W., Hatfield, J. S., and Drescher, D. G. (2009) J. Biol. Chem. 284,
      3227-3238). We now show that Ca(2+)-dependent interaction of the organ of Corti
      HCN1 and protocadherin 15 CD3 is mediated by amino-terminal sequence specific to
      HCN1 and is not replicated by analogous specific peptides for HCN2 or HCN4 nor by
      amino-terminal sequence conserved across HCN isoforms utilized in channel
      formation. Furthermore, the HCN1-specific peptide binds both phosphatidylinositol
      (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate but not
      phosphatidylinositol 4-phosphate. Singly isolated cochlear inner and outer hair
      cells express HCN1 transcript, and HCN1 and HCN2 protein is immunolocalized to
      hair-cell stereocilia by both z-stack confocal and pre-embedding EM immunogold
      microscopy, with stereociliary tip-link and subcuticular plate sites.
      Quantitative PCR indicates HCN1/HCN2/HCN3/HCN4 = 9:9:1:89 in OC of the wild-type
      mouse, with HCN4 protein primarily attributable to inner sulcus cells. A mutant
      form of HCN1 mRNA and protein is expressed in the OC of an HCN1 mutant,
      corresponding to a full-length sequence with the in-frame deletion of pore-S6
      domains, predicted by construct. The mutant transcript of HCN1 is ~9-fold
      elevated relative to wild-type levels, possibly representing molecular
      compensation, with unsubstantial changes in HCN2, HCN3, and HCN4.
      Immunoprecipitation protocols indicate alternate interactions of full-length
      proteins; HCN1 can interact with protocadherin 15 CD3 and F-actin-binding filamin
      A forming a complex that does not include HCN2, or HCN1 can interact with HCN2
      forming a complex without protocadherin 15 CD3 but including F-actin-binding
      fascin-2.

PMID- 22948145
TI  - Structure and mode of peptide binding of pheromone receptor PrgZ.
AB  - We present the crystal structure of the pheromone receptor protein PrgZ from
      Enterococcus faecalis in complex with the heptapeptide cCF10 (LVTLVFV), which is
      used in signaling between conjugative recipient and donor cells. Comparison of
      PrgZ with homologous oligopeptide-binding proteins (AppA and OppA) explains the
      high specificity of PrgZ for hydrophobic heptapeptides versus the promiscuity of
      peptide binding in the homologous proteins.

PMID- 22948146
TI  - Subtype-specific modulation of acid-sensing ion channel (ASIC) function by 2
      guanidine-4-methylquinazoline.
AB  - Acid-sensing ion channels (ASICs) are neuronal Na(+)-selective channels that are
      transiently activated by extracellular acidification. ASICs are involved in fear
      and anxiety, learning, neurodegeneration after ischemic stroke, and pain
      sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently
      shown to open ASIC3 at physiological pH. We have investigated the mechanisms
      underlying this effect and the possibility that GMQ may alter the function of
      other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more
      acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite
      direction and is accompanied by a decrease in its steepness. GMQ also induces an
      acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As
      a consequence, the activation and inactivation curves of ASIC3 but not other
      ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window
      current. At concentrations >1 mM, GMQ decreases maximal peak currents by reducing
      the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of
      ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the
      GMQ effects on inactivation but not activation. This suggests that this residue
      is involved in the consequences of GMQ binding rather than in the binding
      interaction itself. This study describes the mechanisms underlying the effects of
      a novel class of ligands that modulate the function of all ASICs as well as
      activate ASIC3 at physiological pH.

PMID- 22948147
TI  - Afadin is required for maintenance of dendritic structure and excitatory tone.
AB  - The dendritic field of a neuron, which is determined by both dendritic
      architecture and synaptic strength, defines the synaptic input of a cell. Once
      established, a neuron's dendritic field is thought to remain relatively stable
      throughout a cell's lifetime. Perturbations in a dendritic structure or
      excitatory tone of a cell and thus its dendritic field are cellular alterations
      thought to be correlated with a number of psychiatric disorders. Although several
      proteins are known to regulate the development of dendritic arborization, much
      less is known about the mechanisms that maintain dendritic morphology and
      synaptic strength. In this study, we find that afadin, a component of N
      cadherin.beta-catenin.alpha-N-catenin adhesion complexes, is required for the
      maintenance of established dendritic arborization and synapse number. We further
      demonstrate that afadin directly interacts with AMPA receptors and that loss of
      this protein reduces the surface expression of GluA1- and GluA2-AMPA receptor
      subunits. Collectively, these data suggest that afadin is required for the
      maintenance of dendritic structure and excitatory tone.

PMID- 22948148
TI  - C-terminal domains of N-methyl-D-aspartic acid receptor modulate unitary channel
      conductance and gating.
AB  - NMDA receptors (NRs) are glutamate-gated calcium-permeable channels that are
      essential for normal synaptic transmssion and contribute to neurodegeneration.
      Tetrameric proteins consist of two obligatory GluN1 (N1) and two GluN2 (N2)
      subunits, of which GluN2A (2A) and GluN2B (2B) are prevalent in adult brain. The
      intracellularly located C-terminal domains (CTDs) make a significant portion of
      mass of the receptors and are essential for plasticity and excitotoxicity, but
      their functions are incompletely defined. Recent evidence shows that truncation
      of the N2 CTD alters channel kinetics; however, the mechanism by which this
      occurs is unclear. Here we recorded activity from individual NRs lacking the CTDs
      of N1, 2A, or 2B and determined the gating mechanisms of these receptors.
      Receptors lacking the N1 CTDs had larger unitary conductance and faster
      deactivation kinetics, receptors lacking the 2A or 2B CTDs had longer openings
      and longer desensitized intervals, and the first 100 amino acids of the N2 CTD
      were essential for these changes. In addition, receptors lacking the CTDs of
      either 2A or 2B maintained isoform-specific kinetic differences and swapping CTDs
      between 2A and 2B had no effect on single-channel properties. Based on these
      results, we suggest that perturbations in the CTD can modify the NR-mediated
      signal in a subunit-dependent manner, in 2A these effects are most likely
      mediated by membrane-proximal residues, and the isoform-specific biophysical
      properties conferred by 2A and 2B are CTD-independent. The kinetic mechanisms we
      developed afford a quantitative approach to understanding how the intracellular
      domains of NR subunits can modulate the responses of the receptor.

PMID- 22948149
TI  - Characterization of conformation-dependent prion protein epitopes.
AB  - Whereas prion replication involves structural rearrangement of cellular prion
      protein (PrP(C)), the existence of conformational epitopes remains speculative
      and controversial, and PrP transformation is monitored by immunoblot detection of
      PrP(27-30), a protease-resistant counterpart of the pathogenic scrapie form
      (PrP(Sc)) of PrP. We now describe the involvement of specific amino acids in
      conformational determinants of novel monoclonal antibodies (mAbs) raised against
      randomly chimeric PrP. Epitope recognition of two mAbs depended on polymorphisms
      controlling disease susceptibility. Detection by one, referred to as PRC5,
      required alanine and asparagine at discontinuous mouse PrP residues 132 and 158,
      which acquire proximity when residues 126-218 form a structured globular domain.
      The discontinuous epitope of glycosylation-dependent mAb PRC7 also mapped within
      this domain at residues 154 and 185. In accordance with their conformational
      dependence, tertiary structure perturbations compromised recognition by PRC5,
      PRC7, as well as previously characterized mAbs whose epitopes also reside in the
      globular domain, whereas conformation-independent epitopes proximal or distal to
      this region were refractory to such destabilizing treatments. Our studies also
      address the paradox of how conformational epitopes remain functional following
      denaturing treatments and indicate that cellular PrP and PrP(27-30) both renature
      to a common structure that reconstitutes the globular domain.

PMID- 22948150
TI  - Acid-sensitive TWIK and TASK two-pore domain potassium channels change ion
      selectivity and become permeable to sodium in extracellular acidification.
AB  - Two-pore domain K(+) channels (K2P) mediate background K(+) conductance and play
      a key role in a variety of cellular functions. Among the 15 mammalian K2P
      isoforms, TWIK-1, TASK-1, and TASK-3 K(+) channels are sensitive to extracellular
      acidification. Lowered or acidic extracellular pH (pH(o)) strongly inhibits
      outward currents through these K2P channels. However, the mechanism of how low
      pH(o) affects these acid-sensitive K2P channels is not well understood. Here we
      show that in Na(+)-based bath solutions with physiological K(+) gradients,
      lowered pH(o) largely shifts the reversal potential of TWIK-1, TASK-1, and TASK-3
      K(+) channels, which are heterologously expressed in Chinese hamster ovary cells,
      into the depolarizing direction and significantly increases their Na(+) to K(+)
      relative permeability. Low pH(o)-induced inhibitions in these acid-sensitive K2P
      channels are more profound in Na(+)-based bath solutions than in channel
      impermeable N-methyl-D-glucamine-based bath solutions, consistent with increases
      in the Na(+) to K(+) relative permeability and decreases in electrochemical
      driving forces of outward K(+) currents of the channels. These findings indicate
      that TWIK-1, TASK-1, and TASK-3 K(+) channels change ion selectivity in response
      to lowered pH(o), provide insights on the understanding of how extracellular
      acidification modulates acid-sensitive K2P channels, and imply that these acid
      sensitive K2P channels may regulate cellular function with dynamic changes in
      their ion selectivity.

PMID- 22948151
TI  - Identification of HEXIM1 as a positive regulator of p53.
AB  - Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the
      inhibitor of positive transcription elongation factor b (P-TEFb), which regulates
      the transcription elongation of RNA polymerase II and controls 60-70% of mRNA
      synthesis. Our previous studies show that HEXIM1 interacts with two key p53
      regulators, nucleophosmin and human double minute-2 protein (HDM2), implying a
      possible connection between HEXIM1 and the p53 signaling pathway. Here we report
      the interaction between p53 and HEXIM1 in breast cancer, acute myeloid leukemia,
      and colorectal carcinoma cells. The C-terminal regions of p53 and HEXIM1 are
      required for the protein-protein interaction. Overexpression of HEXIM1 prevents
      the ubiquitination of p53 by HDM2 and enhances the protein stability of p53,
      resulting in up-regulation of p53 target genes, such as Puma and p21. Induction
      of p53 can be achieved by several means, such as UV radiation and treatment with
      anti-cancer agents (including doxorubicin, etoposide, roscovitine, flavopiridol,
      and nutlin-3). Under all the conditions examined, elevated protein levels of p53
      are found to associate with the increased p53-HEXIM1 interaction. In addition,
      knockdown of HEXIM1 significantly inhibits the induction of p53 and releases the
      cell cycle arrest caused by p53. Finally, the transcription of the p53 target
      genes is regulated by HEXIM1 in a p53-dependent fashion. Our results not only
      identify HEXIM1 as a positive regulator of p53, but also propose a novel
      molecular mechanism of p53 activation caused by the anti-cancer drugs and
      compounds.

PMID- 22948152
TI  - Bidirectional coupling between ryanodine receptors and Ca2+ release-activated
      Ca2+ (CRAC) channel machinery sustains store-operated Ca2+ entry in human T
      lymphocytes.
AB  - The expression and functional significance of ryanodine receptors (RyR) were
      investigated in resting and activated primary human T cells. RyR1, RyR2, and RyR3
      transcripts were detected in human T cells. RyR1/2 transcript levels increased,
      whereas those of RyR3 decreased after T cell activation. RyR1/2 protein
      immunoreactivity was detected in activated but not in resting T cells. The RyR
      agonist caffeine evoked Ca(2+) release from the intracellular store in activated
      T cells but not in resting T cells, indicating that RyR are functionally up
      regulated in activated T cells compared with resting T cells. In the presence of
      store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+) release-activated
      Ca(2+) (CRAC) channels, RyR blockers reduced the Ca(2+) leak from the endoplasmic
      reticulum (ER) and the magnitude of SOCE, suggesting that a positive feedback
      relationship exists between RyR and CRAC channels. Overexpression of
      fluorescently tagged RyR2 and stromal interaction molecule 1 (STIM1), an ER
      Ca(2+) sensor gating CRAC channels, in HEK293 cells revealed that RyR are co
      localized with STIM1 in the puncta formed after store depletion. These data
      indicate that in primary human T cells, the RyR are coupled to CRAC channel
      machinery such that SOCE activates RyR via a Ca(2+)-induced Ca(2+) release
      mechanism, which in turn reduces the Ca(2+) concentration within the ER lumen in
      the vicinity of STIM1, thus facilitating SOCE by reducing store-dependent CRAC
      channel inactivation. Treatment with RyR blockers suppressed activated T cell
      expansion, demonstrating the functional importance of RyR in T cells.

PMID- 22948153
TI  - Adiponectin induces pro-inflammatory programs in human macrophages and CD4+ T
      cells.
AB  - Abundant experimental and clinical data support a modulatory role for adiponectin
      in inflammation, dysmetabolism, and disease. Because the activation of cells
      involved in innate and adaptive immunity contributes to the pathogenesis of
      diseases such as atherosclerosis and obesity, this study investigated the role of
      adiponectin in human macrophage polarization and T cell differentiation.
      Examination of the adiponectin-induced transcriptome in primary human macrophages
      revealed that adiponectin promotes neither classical (M1) nor alternative (M2)
      macrophage activation but elicits a pro-inflammatory response that resembles M1
      more closely than M2. Addition of adiponectin to polyclonally activated CD4(+) T
      lymphocytes did not affect cell proliferation but induced mRNA expression and
      protein secretion of interferon (IFN)-gamma and interleukin (IL)-6. Adiponectin
      treatment of CD4(+) T cells increased phosphorylation of p38 mitogen-activated
      protein kinase (MAPK) and signal transducer and activation of transcription
      (STAT) 4 and augmented T-bet expression. Inhibition of p38 with SB203580
      abrogated adiponectin-induced IFN-gamma production, indicating that adiponectin
      enhances T(H)1 differentiation through the activation of the p38-STAT4-T-bet
      axis. Collectively, our results demonstrate that adiponectin can induce pro
      inflammatory functions in isolated macrophages and T cells, concurring with
      previous observations that adiponectin induces a limited program of inflammatory
      activation that likely desensitizes these cells to further pro-inflammatory
      stimuli.

PMID- 22948154
TI  - Grb14 is a negative regulator of CEACAM3-mediated phagocytosis of pathogenic
      bacteria.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is a
      phagocytic receptor on human granulocytes, which mediates the opsonin-independent
      recognition and internalization of a restricted set of Gram-negative bacteria
      such as Neisseria gonorrhoeae. In an unbiased screen using a SH2 domain
      microarray we identified the SH2 domain of growth factor receptor-bound protein
      14 (Grb14) as a novel binding partner of CEACAM3. Biochemical assays and
      microscopic studies demonstrated that the Grb14 SH2 domain promoted the rapid
      recruitment of this adaptor protein to the immunoreceptor-based activation motif
      (ITAM)-like sequence within the cytoplasmic domain of CEACAM3. Furthermore, FRET
      FLIM analyses confirmed the direct association of Grb14 and CEACAM3 in intact
      cells at the sites of bacteria-host cell contact. Knockdown of endogenous Grb14
      by RNA interference as well as Grb14 overexpression indicate an inhibitory role
      for this adapter protein in CEACAM3-mediated phagocytosis. Therefore, Grb14 is
      the first negative regulator of CEACAM3-initiated bacterial phagocytosis and
      might help to focus granulocyte responses to the subcellular sites of pathogen
      host cell contact.

PMID- 22948155
TI  - Cross-talk between Rho-associated kinase and cyclic nucleotide-dependent kinase
      signaling pathways in the regulation of smooth muscle myosin light chain
      phosphatase.
AB  - Ca(2+) sensitization of smooth muscle contraction depends upon the activities of
      protein kinases, including Rho-associated kinase, that phosphorylate the myosin
      phosphatase targeting subunit (MYPT1) at Thr(697) and/or Thr(855) (rat sequence
      numbering) to inhibit phosphatase activity and increase contractile force. Both
      Thr residues are preceded by the sequence RRS, and it has been suggested that
      phosphorylation at Ser(696) prevents phosphorylation at Thr(697). However, the
      effects of Ser(854) and dual Ser(696)-Thr(697) and Ser(854)-Thr(855)
      phosphorylations on myosin phosphatase activity and contraction are unknown. We
      characterized a suite of MYPT1 proteins and phosphospecific antibodies for
      specificity toward monophosphorylation events (Ser(696), Thr(697), Ser(854), and
      Thr(855)), Ser phosphorylation events (Ser(696)/Ser(854)) and dual Ser/Thr
      phosphorylation events (Ser(696)-Thr(697) and Ser(854)-Thr(855)). Dual
      phosphorylation at Ser(696)-Thr(697) and Ser(854)-Thr(855) by cyclic nucleotide
      dependent protein kinases had no effect on myosin phosphatase activity, whereas
      phosphorylation at Thr(697) and Thr(855) by Rho-associated kinase inhibited
      phosphatase activity and prevented phosphorylation by cAMP-dependent protein
      kinase at the neighboring Ser residues. Forskolin induced phosphorylation at
      Ser(696), Thr(697), Ser(854), and Thr(855) in rat caudal artery, whereas U46619
      induced Thr(697) and Thr(855) phosphorylation and prevented the Ser
      phosphorylation induced by forskolin. Furthermore, pretreatment with forskolin
      prevented U46619-induced Thr phosphorylations. We conclude that cross-talk
      between cyclic nucleotide and RhoA signaling pathways dictates the
      phosphorylation status of the Ser(696)-Thr(697) and Ser(854)-Thr(855) inhibitory
      regions of MYPT1 in situ, thereby regulating the activity of myosin phosphatase
      and contraction.

PMID- 22948156
TI  - Engineering of sialylated mucin-type O-glycosylation in plants.
AB  - Proper N- and O-glycosylation of recombinant proteins is important for their
      biological function. Although the N-glycan processing pathway of different
      expression hosts has been successfully modified in the past, comparatively little
      attention has been paid to the generation of customized O-linked glycans. Plants
      are attractive hosts for engineering of O-glycosylation steps, as they contain no
      endogenous glycosyltransferases that perform mammalian-type Ser/Thr glycosylation
      and could interfere with the production of defined O-glycans. Here, we produced
      mucin-type O-GalNAc and core 1 O-linked glycan structures on recombinant human
      erythropoietin fused to an IgG heavy chain fragment (EPO-Fc) by transient
      expression in Nicotiana benthamiana plants. Furthermore, for the generation of
      sialylated core 1 structures constructs encoding human polypeptide:N
      acetylgalactosaminyltransferase 2, Drosophila melanogaster core 1 beta1,3
      galactosyltransferase, human alpha2,3-sialyltransferase, and Mus musculus
      alpha2,6-sialyltransferase were transiently co-expressed in N. benthamiana
      together with EPO-Fc and the machinery for sialylation of N-glycans. The
      formation of significant amounts of mono- and disialylated O-linked glycans was
      confirmed by liquid chromatography-electrospray ionization-mass spectrometry.
      Analysis of the three EPO glycopeptides carrying N-glycans revealed the presence
      of biantennary structures with terminal sialic acid residues. Our data
      demonstrate that N. benthamiana plants are amenable to engineering of the O
      glycosylation pathway and can produce well defined human-type O- and N-linked
      glycans on recombinant therapeutics.

PMID- 22948157
TI  - Prolyl hydroxylase 3 (PHD3) modulates catabolic effects of tumor necrosis factor
      alpha (TNF-alpha) on cells of the nucleus pulposus through co-activation of
      nuclear factor kappaB (NF-kappaB)/p65 signaling.
AB  - Recent studies suggest a differential role of prolyl hydroxylase (PHD) isoforms
      in controlling hypoxia-inducible factor (HIF)-alpha degradation and activity in
      nucleus pulposus (NP) cells. However, the regulation and function of PHDs under
      inflammatory conditions that characterize disc disease are not yet known. Here,
      we show that in NP cells, TNF-alpha and IL-1beta induce PHD3 expression through
      NF-kappaB. Lentiviral delivery of Sh-p65 and Sh-IKKbeta confirms that cytokine
      mediated PHD3 expression is NF-kappaB-dependent. It is noteworthy that although
      both cytokines induce HIF activity, mechanistic studies using Sh-HIF-1alpha and
      PHD3 promoter/enhancer constructs harboring well characterized hypoxia response
      element (HRE) show lack of HIF involvement in cytokine-mediated PHD3 expression.
      Loss-of-function studies clearly indicate that PHD3 serves as a co-activator of
      NF-kappaB signaling activity in NP cells; PHD3 interacts with, and co-localizes
      with, p65. We observed that when PHD3 is silenced, there is a significant
      decrease in TNF-alpha-induced expression of catabolic markers that include
      ADAMTS5, syndecan4, MMP13, and COX2, and at the same time, there is restoration
      of aggrecan and collagen type II expression. It is noteworthy that hydroxylase
      function of PHDs is not required for mediating cytokine-dependent gene
      expression. These findings show that by enhancing the activity of inflammatory
      cytokines, PHD3 may serve a critical role in degenerative disc disease.

PMID- 22948158
TI  - Toll-like receptor 2 (TLR2), transforming growth factor-beta, hyaluronan (HA),
      and receptor for HA-mediated motility (RHAMM) are required for surfactant protein
      A-stimulated macrophage chemotaxis.
AB  - The innate immune system protects the host from bacterial and viral invasion.
      Surfactant protein A (SPA), a lung-specific collectin, stimulates macrophage
      chemotaxis. However, the mechanisms regulating this function are unknown.
      Hyaluronan (HA) and its receptors RHAMM (receptor for HA-mediated motility,
      CD168) and CD44 also regulate cell migration and inflammation. We therefore
      examined the role of HA, RHAMM, and CD44 in SPA-stimulated macrophage chemotaxis.
      Using antibody blockade and murine macrophages, SPA-stimulated macrophage
      chemotaxis was dependent on TLR2 but not the other SPA receptors examined. Anti
      TLR2 blocked SPA-induced production of TGFbeta. In turn, TGFbeta1-stimulated
      chemotaxis was inhibited by HA-binding peptide and anti-RHAMM antibody but not
      anti-TLR2 antibody. Macrophages from TLR2(-/-) mice failed to migrate in response
      to SPA but responded normally to TGFbeta1 and HA, effects that were blocked by
      anti-RHAMM antibody. Macrophages from WT and CD44(-/-) mice had similar responses
      to SPA, whereas those from RHAMM(-/-) mice had decreased chemotaxis to SPA,
      TGFbeta1, and HA. In primary macrophages, SPA-stimulated TGFbeta production was
      dependent on TLR2, JNK, and ERK but not p38. Pam3Cys, a specific TLR2 agonist,
      stimulated phosphorylation of JNK, ERK, and p38, but only JNK and ERK inhibition
      blocked Pam3Cys-stimulated chemotaxis. We have uncovered a novel pathway for SPA
      stimulated macrophage chemotaxis where SPA stimulation via TLR2 drives JNK- and
      ERK-dependent TGFbeta production. TGFbeta1, in turn, stimulates macrophage
      chemotaxis in a RHAMM and HA-dependent manner. These findings are highly relevant
      to the regulation of innate immune responses by SPA with key roles for specific
      components of the extracellular matrix.

PMID- 22948159
TI  - Constant domain-regulated antibody catalysis.
AB  - Some antibodies contain variable (V) domain catalytic sites. We report the
      superior amide and peptide bond-hydrolyzing activity of the same heavy and light
      chain V domains expressed in the IgM constant domain scaffold compared with the
      IgG scaffold. The superior catalytic activity of recombinant IgM was evident
      using two substrates, a small model peptide that is hydrolyzed without
      involvement of high affinity epitope binding, and HIV gp120, which is recognized
      specifically by noncovalent means prior to the hydrolytic reaction. The catalytic
      activity was inhibited by an electrophilic phosphonate diester, consistent with a
      nucleophilic catalytic mechanism. All 13 monoclonal IgMs tested displayed robust
      hydrolytic activities varying over a 91-fold range, consistent with expression of
      the catalytic functions at distinct levels by different V domains. The catalytic
      activity of polyclonal IgM was superior to polyclonal IgG from the same sera,
      indicating that on average IgMs express the catalytic function at levels greater
      than IgGs. The findings indicate a favorable effect of the remote IgM constant
      domain scaffold on the integrity of the V-domain catalytic site and provide a
      structural basis for conceiving antibody catalysis as a first line immune
      function expressed at high levels prior to development of mature IgG class
      antibodies.

PMID- 22948160
TI  - TRIM56 is an essential component of the TLR3 antiviral signaling pathway.
AB  - Members of the tripartite motif (TRIM) proteins are being recognized as important
      regulators of host innate immunity. However, specific TRIMs that contribute to
      TLR3-mediated antiviral defense have not been identified. We show here that
      TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56
      substantially potentiated extracellular dsRNA-induced expression of interferon
      (IFN)-beta and interferon-stimulated genes (ISGs), while knockdown of TRIM56
      greatly impaired activation of IRF3, induction of IFN-beta and ISGs, and
      establishment of an antiviral state by TLR3 ligand and severely compromised TLR3
      mediated chemokine induction following infection by hepatitis C virus. The
      ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase
      activity of TRIM56. Rather, it correlated with a physical interaction between
      TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the
      TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN
      response. Together, our data demonstrate TRIM56 is an essential component of the
      TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate
      antiviral immunity.

PMID- 22948161
TI  - WITHDRAWN: Specific antigen vaccination modulates memory B cell activities.
AB  - The manuscript was withdrawn by the Author.

PMID- 22948162
TI  - Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome
      activation.
AB  - The NLRP3 inflammasome is a key component of the innate immune response to
      pathogenic infection and tissue damage. It is also involved in the pathogenesis
      of a number of human diseases, including gouty arthritis, silicosis,
      atherosclerosis, and type 2 diabetes. The assembly of the NLRP3 inflammasome
      requires a priming signal derived from pattern recognition or cytokine receptors,
      followed by a second signal derived from extracellular ATP, pore-forming toxins,
      or crystalline materials. How these two signals activate the NLRP3 inflammasome
      is not yet clear. Here, we show that in mouse macrophages, signaling by the
      pattern recognition receptor TLR4 through MyD88 can rapidly and non
      transcriptionally prime NLRP3 by stimulating its deubiquitination. This process
      is dependent on mitochondrial reactive oxygen species production and can be
      inhibited by antioxidants. We further show that signaling by ATP can also induce
      deubiquitination of NLRP3 by a mechanism that is not sensitive to antioxidants.
      Pharmacological inhibition of NLRP3 deubiquitination completely blocked NLRP3
      activation in both mouse and human cells, indicating that deubiquitination of
      NLRP3 is required for its activation. Our findings suggest that NLRP3 is
      activated by a two-step deubiquitination mechanism initiated by Toll-like
      receptor signaling and mitochondrial reactive oxygen species and further
      potentiated by ATP, which could explain how NLRP3 is activated by diverse danger
      signals.

PMID- 22948163
TI  - Glucose-promoted Zn-based metal-organic framework/graphene oxide composites for
      hydrogen sulfide removal.
AB  - Zinc-based metal-organic frameworks/graphene oxide (MOF-5/GO) composites were
      synthesized via the solvothermal method. The materials were characterized by
      scanning electron microscopy (SEM), nitrogen adsorption, X-ray diffraction (XRD),
      Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron
      spectroscopy (XPS), and their performances for hydrogen sulfide (H(2)S) removal
      were evaluated by dynamic testing at room temperature. The composites exhibit
      microporous structure with a small amount of mesopores, and the structure is
      highly dependent on the amount of GO loaded. The surface area and pore volume
      first increase and then decrease with increasing GO, reaching the maximum value
      when the GO ratio is 5.25%. The composites exhibit high adsorption capacities for
      H(2)S, with the maximum uptakes reaching up to 130.1 mg/g. Although the loading
      of GO makes a contribution to the enhancement of dispersive force in the porous
      structure, it leads to the crystal distortion of MOF-5. The introduction of
      glucose can restrain this distortion to maintain the structure stability. A good
      match between GO and glucose have a well synergy effect to develop the porous
      structure, resulting in the highest H(2)S adsorption capacity.

PMID- 22948165
TI  - [Influence of compendium of Materia Medica on the materia medica in the late
      period of the Chosun Dynasty].
AB  - In this paper, I investigated the influence of Compendium of Materia Medica (CM)
      on Records for Rural Life of Chosun Gentlemen (RRC), and refuted Miki Sakae's
      opinion, CM did not have much impact on the Materia Medica in the late period of
      the Chosun Dynasty. When Li Shizhen published CM, it resulted in a shift of
      mainstream of Materia Medica in Eastern Asia from Classified Emergency Materia
      Medica to CM and a new categorizing system of Materia Medica by CM led to the
      division of Materia Medica into medicine and natural history. It is obvious that
      doctors of the Chosun Dynasty also adopted the latest achievements of Materia
      Medica by CM, but so far there have been few studies to clarify this. Seo yugu
      was a scholar of the Realist School of Confucianism during the late period of the
      Chosun Dynasty, and RRC is his representative work. RRC is a massive encyclopedia
      of natural history that covers vast areas of science from agriculture,
      floriculture, writing and drawing, architecture, diet, and medicine, among others
      which absorbed the achievements of CM, the best Materia Medica book at that time.
      Miki  Sakae also highly regarded the encyclopedic knowledge of RRC, but devalued
      the results of Materia Medica. He only described a part of RRC's Materia Medica,
      nurturing volume, on the view of life nurturing and mentioned that it had been
      strongly influenced by China. According to this study, a large portion of RRC,
      especially regarding Materia Medica, depends on CM. Seo yugu had accepted the
      categorizing system and new medicinal information of CM, at the same time he
      modified the categorizing system of CM practically by the subject of each volume
      of RRC. We can find many quotations of CM except the nurturing volume, but other
      books, Treasured Mirror of Eastern Medicine, Materia Medica for Relief of Famines
      are also quoted. Furthermore, Seo yugu emphasized the differences of natural
      environments between Chosun and China, and specified the editing criteria, "to be
      useful in Chosun." This is the most obvious evidence that Materia Medica of
      Chosun had not remained in the framework of Treasured Mirror of Eastern Medicine
      which succeeded Classified Emergency Materia Medica, but had been developed into
      medicine and natural history based on CM.

PMID- 22948164
TI  - Chromosomal translocations among the healthy human population: implications in
      oncogenesis.
AB  - Chromosomal translocations are characteristic features of many cancers,
      especially lymphoma and leukemia. However, recent reports suggest that many
      chromosomal translocations can be found in healthy individuals, although the
      significance of this observation is still not clear. In this review, we summarize
      recent studies on chromosomal translocations in healthy individuals carried out
      in different geographical areas of the world and discuss the relevance of the
      observation with respect to oncogenesis.

PMID- 22948166
TI  - [Introduction of Western medicine and change of term of "tuberculosis" in Korea].
AB  - In this article, I figured out 'tuberculosis' as prominent example of
      relationship between introduction of western medicine and change of disease term.
      Tuberculosis is one of the examples of incomplete substitution of
      oriental/lay/non-scientific disease term by western/scientific disease term in
      colonial society. Western medicine practitioner in Korea had started to find and
      treat tuberculosis right after Koch's discovery of the tubercule bacillus (1882).
      It was 'Kyulhak' that includes germ theory and the newest medical knowledge, but
      'heasobyun'which means coughing disease, and 'bujockjung'which means consumptive
      disease were also newly introduced as lay term. There also had been traditional
      term 'nochae' which already recognized as similar term of phthisis, redefined as
      only oriental medicine term after introduction of western medicine. Despite of
      reception of the term 'kyulhak' in Korean society, these terms were widely used
      instead of 'kyulhak' during the colonial period.

PMID- 22948167
TI  - [Zhuzhiqunzheng, the Jesuit translation of Western medicine and its influence on
      Korean and Chinese intellectuals].
AB  - The Jesuits were great transmitters of Western science to East Asia in the 17th
      and 18th century. In 1636, a German Jesuit missionary Johann Adam Schall von Bell
      (1591-1666) published a book titled Zhuzhiqunzheng (Hundreds of Signs Testifying
      Divine Providence). The book was not Adam Schall's own writing, but it was the
      Chinese translation of De providentia numinis (1613) of Leonardus Lessius (1554
      1623) who was also a Jesuit scholar. The book was a religious work which
      particularly aimed at converting the pagans to the Christianity by presenting
      them with hundreds of signs testifying the divine providence. One group of the
      signs is those manifested in the human body. The bodily signs in question include
      anatomical structures and physiological processes. It gives a brief survey of
      bodily structures with bones and muscles. The translator had much difficulties in
      explaining muscles for there was no corresponding concept in Chinese medicine.
      The theory of human physiology was a simplified version of medieval Galenism.
      Three kinds of pneuma were translated into three kinds of Qi respectively.
      'Natural pneuma'was translated into 'Qi of the body nature', 'vital pneuma' into
      'Qi of life and nourishing', 'psychic pneuma' into 'Qi of movement and
      consciousness'. The book of Schall von Bell and other books on Western science
      written in Chinese were also imported to Korea during the 17th and 18th century.
      Unlike China, Korea was very hostile to Christianity and no Jesuit could enter
      Korea. Only the books on Western science could be imported. The books, which were
      called Books on Western Learning, were circulated and read among the progressive
      Confucian literati. However, Western medicine thus introduced had little
      influence on the traditional medicine of East Asia. However, some intellectuals
      paid attention to the physiological theory, in particular the theory of brain
      centrism, which fueled a philosophical debate among Korean intellectuals of the
      time.

PMID- 22948168
TI  - [A social history of carbon monoxide poisoning in Korea in 1960s: from an
      accident    due to carelessness to a social disease].
AB  - This paper deals with social history of carbon monoxide poisoning in Korea in
      1960s. From the mid 1950s, Korean society began to use coal briquettes (Yeontan)
      for fuel for cooking and heating in the winter, especially in urban area. As the
      use of coal briquettes replaced fire woods which had been used as fuel in
      traditional Korean society for centuries, incidence and deaths from carbon
      monoxide poisoning increased dramatically during the 1960s. The coal briquettes
      were used to heat the living rooms through "Ondol" arrangement. The coal
      briquettes at the kitchen place make the heated air and smoke, which pass through
      the horizontal space under a stone floor of the room and escape through chimney
      at the opposite site of the kitchen. This Ondol system could make leakage of
      carbon monoxide easily and thereby kill people who sleep in the room. In the
      1960s, carbon monoxide poisoning by briquettes gas was a serious health problem
      to kill more people than all of the infectious diseases. It was a unique and very
      serious health hazard in 1960s Korea. No other place in the world has experienced
      such a high mortality and incidence from the briquettes gas as in Korea.
      Employing newspaper articles and epidemiological papers, this paper analyzes how
      the Korean society experienced and perceived carbon monoxide poisoning (CO
      poisoning) in 1960s. It also follows how the perception changed over time and how
      the changes affected social responses to CO poisoning. In the early 1960s, the CO
      poisoning was perceived as an accident due to carelessness of the people who did
      not fix the leakages of the Ondol system or that of the people who built the
      Ondol improperly. Mostly CO poisoning was the casualty caused by carelessness and
      ignorance of the poor class. The prevention measure was mainly education which
      would enlighten the ignorant so that they care about CO poisoning and their
      lives. It was the victims who were to be blamed, for they caused the their
      poisoning with their own carelessness. Since CO poisoning was perceived as
      preventable with a good care, people were optimistic about the prevention of the
      CO poisoning. In the late 1960s, however, the perception of CO poisoning changed
      as the epidemiological studies demonstrated meteorological, social, economical,
      and cultural factors were related to the poisoning. As CO poisoning was regarded
      not as an accident due to carelessness but as a social disease, the Korean
      government began to take various measures for its control including surveillance
      and punishment, education and certification of those who made Ondol, and funding
      research for detoxification of the poisoning. In spite of the state's
      intervention, the number of CO poisoning cases drastically increased every year.
      At the end of 1960s, in contrast to the optimism of the early 1960s, the outlook
      of CO poisoning control was grim. It was merely a beginning of huge epidemic of
      CO poisoning in 1970s and 1980s in Korea.

PMID- 22948169
TI  - We are not joking: need for controls in reports of dating violence.
AB  - Underreporting of intimate partner aggression is an important issue in the
      interpretation of self-reports of such aggression, especially by males. However,
      both males and females are less likely to report negative behaviors about
      themselves than about their partners. With 863 adolescents from Madrid, social
      desirability had a small but significant association with reports of dating
      aggression, but covariance corrections for social desirability did not alter the
      conclusions about such aggression. Using uncorrected or corrected means for
      social desirability, males engage in more sexual aggression against their
      partners and females engage in more psychological and physical aggression.
      Maximal dyadic reports based on reports by either self or partner significantly
      increased the rates of aggression, although conclusions about perpetration and
      victimization did not differ with this correction. Rates of aggression dropped
      roughly half when corrected for aggression in a joking context, but more females
      still reported engaging in physical aggression against their partners. The
      corrections one wishes to use depend upon the sample under study-i.e., adolescent
      versus adult populations-and one's research or clinical question, but the use of
      social desirability controls seems ill-founded. Finally, there is a need for in
      depth interviews with both partners in dating relationships to determine more
      about the contextual factors associated with dating aggression and to assist in
      knowing what correction factors seem most valid.

PMID- 22948170
TI  - Psychopathy-related personality traits and shame management strategies in
      adolescents.
AB  - The purpose of this study was to examine whether there is a correlation between
      the amount of psychopathy-related personality traits and the type of shame
      management in adolescents. Two hypotheses were examined; first, that there is a
      positive correlation between psychopathy-related personality traits and more
      unconscious and externalized shame management strategies, and second, that there
      is a negative correlation between psychopathy-related personality traits and more
      conscious and internalized shame management strategies. Gender differences were
      also examined. In total, 236 participants were available for the study. All were
      secondary-level students, aged 16 to 21 years. Of these, 196 were examined: 96
      were male and 100 female. The study used two self-assessment forms-the Youth
      Psychopathic traits Inventory (YPI) and the Compass of Shame Scale (CoSS)-to
      measure the relevant personality characteristics. The results indicated gender
      differences, which led to all the analyses being conducted separately for males
      and females. Support was found for the study's first hypothesis, but not for the
      second, which was true for both males and females. Our results may have
      implications for the treatment of adolescents with a high percentage of
      psychopathy-related personality traits; they also indicate the need for more
      research on the association between psychopathy and shame management.

PMID- 22948171
TI  - Increased level of antibodies cross-reacting with Ves v 5 and CRISP-2 in MAR
      positive patients.
AB  - BACKGROUND: Anti-sperm antibodies (ASA) have been described to be involved in
      immunological infertility. A possible antigen for ASA is the human cysteine-rich
      secretory protein 2 (CRISP-2), a sperm surface protein important in sperm-oocyte
      interaction. Furthermore, anti-CRISP-2 antibodies were shown to decrease
      fertility rates in vitro. Recently, we have reported cross-reacting antibodies
      recognizing CRISP-2 and antigen 5 from yellow jacket venom (Ves v 5) in human
      serum. METHODS: Here, we investigated anti-Ves v 5 and CRISP-2 antibodies in sera
      from two groups of donors: MAR+ and MAR- patients. RESULTS: A higher incidence of
      allergy against hymenoptera venom was found in MAR+ patients. Interestingly,
      affinity-purified ASA from MAR+ patients' sera reacted against both Ves v 5 and
      CRISP-2, leading to sperm immobilization. Immunofluorescence analysis showed that
      ASA bound to the sperm surface, including the head part where CRISP-2 is
      localized. CONCLUSION: Taken together, these results showed a higher incidence of
      antibodies cross-reacting with Ves v 5 and CRISP-2 in MAR+ patients. This leads
      to the hypothesis that MAR+ patients may have a higher risk to develop wasp
      allergy.

PMID- 22948172
TI  - Effects of seated double-poling ergometer training on aerobic and mechanical
      power in individuals with spinal cord injury.
AB  - OBJECTIVE: To determine whether regular interval training on a seated double
      poling ergometer can increase physical capacity and safely improve performance
      towards maximal level in individuals with spinal cord injury. METHODS: A total of
      13 subjects with spinal cord injury (injury levels T5-L1) performed 30 sessions
      of seated double-poling ergometer training over a period of 10 weeks. Sub-maximal
      and maximal double-poling ergometer tests were performed before (test-retest) and
      after this training period. Oxygen uptake was measured using the Douglas Bag
      system. Three-dimensional kinematics were recorded using an optoelectronic system
      and piezoelectric force sensors were used to register force in both poles.
      RESULTS: The mean intra-class correlation coefficient for test-retest values was
      0.83 (standard deviation 0.11). After training significant improvements were
      observed in people with spinal cord injury in oxygen uptake (22.7%), ventilation
      (20.7%) and blood lactate level (22.0%) during maximal exertion exercises. Mean
      power per stroke and peak pole force increased by 15.4% and 23.7%, respectively.
      At sub-maximal level, significantly lower values were observed in ventilation (
      12.8%) and blood lactate level (-25.0%). CONCLUSION: Regular interval training on
      the seated double-poling ergometer was effective for individuals with spinal cord
      injury below T5 level in terms of improving aerobic capacity and upper-body power
      output. The training was safe and did not cause any overload symptoms.

PMID- 22948173
TI  - Titrated extract of Centella asiatica provides a UVB protective effect by
      altering microRNA expression profiles in human dermal fibroblasts.
AB  - The titrated extract of Centella asiatica (TECA) is a reconstituted mixture
      comprising of asiatic acid, madecassic acid, asiaticoside and madecassoside, and
      is used as a therapeutic agent in wound healing and also as an anti-microbial,
      anticancer and anti-aging agent. Although these properties and the associated
      cell signaling pathways have been elucidated, the cellular mechanism of anti
      photoaging upon ultraviolet (UV) exposure in normal human dermal fibroblasts
      (NHDFs) remains unknown. In this study, we investigated the photoprotective role
      of TECA via microRNA (miRNA) expression profiling analysis. Low dose of TECA did
      not exhibit toxicity and showed a protective effect against UVB irradiation in
      NDHFs. miRNA microarray experiments revealed that specific miRNAs were altered by
      TECA stimulation in UVB-irradiated NHDFs. Functional bioinformatic analysis
      showed that the putative target genes of the altered miRNAs were associated with
      the positive regulation of cell proliferation, anti-apoptosis, small GTPase- and
      Ras-mediated signal transduction and activation of MAPKK. Therefore, these
      results suggest that TECA may serve as a potential natural chemoprotective agent
      against UVB-mediated damage in NHDFs through changes in the expression of
      specific miRNAs.

PMID- 22948174
TI  - A red flag in sarcoidosis: laryngeal obstruction.

PMID- 22948175
TI  - Phenotypic screening reveals topoisomerase I as a breast cancer stem cell
      therapeutic target.
AB  - Cancer stem cells (CSCs) are a subpopulation generally thought to be responsible
      for cancer initiation and progression. Because CSCs are often rare in the total
      tumor cell population and differentiate rapidly when grown in culture, it has
      been challenging to uncover compounds that selectively target CSCs. We previously
      described CSC-emulating cells derived from breast cancer cell lines that
      maintained a stable undifferentiated state. We optimized a phenotypic assay with
      these cells and screened 1,280-bioactive compounds, identifying five that
      preferentially inhibited CSC-like cell proliferation. Using a compound-guided
      target identification approach, we found high topoisomerase I (Topo I) expression
      levels in breast CSC-like cells and primary breast CSCs. Structurally unrelated
      small molecules targeting Topo I preferentially inhibited CSC-like cells. These
      results illustrate the substantial power of this CSC phenotypic screening
      platform and promote Topo I as a potential molecular therapeutic target for
      therapies aimed at expunging CSCs.

PMID- 22948176
TI  - Preterm infant with a catastrophic hemorrhagic-thromboembolic incident.
AB  - Thrombotic disease of the newborn is uncommon but usually associated with serious
      morbidity and mortality. Although the operating mechanisms of coagulation and
      fibrinolysis are the same in all age groups, plasma concentrations of the two
      systems' components are significantly different in neonates compared to children
      and adults. This places neonates at greater risk for thrombosis that may rise
      considerably if a predisposing factor is present or a genetic or medical
      condition predisposing to thrombosis coexists. While marginal, the possibility of
      abnormal bleeding secondary to congenital prothrombotic disorders has been
      described. A significant association between thromboembolic/hemorrhagic disease
      in newborns and each of factor V(Leiden) and prothrombin G20210A mutations has
      been reported. Although not a frequent occurrence in adults and children,
      congenital 'multigenic' thrombophilia is well known. However, the combined
      heterozygote state of both mutations is perhaps underreported in preterm infants.
      We present a severely intrauterine growth-restricted preterm baby born to
      consanguineous parents. He had stroke as part of a generalized bleeding
      thromboembolic incident caused by combined heterozygote mutation of factor
      V(Leiden) and prothrombin G20210A, each of which was then found in a heterozygote
      form in each of the 2 parents.

PMID- 22948177
TI  - Sensitive analysis of DNA methyltransferase based on a hairpin-shaped DNAzyme.
AB  - The analysis of DNA methylation and MTase (methyltransferase) activity is
      important in epigenetic study. We have developed a novel strategy for sensitive
      analysis of MTase activity based on a hairpin shaped DNAzyme; 8-17 DNAzyme
      amplicon has been adopted and found to be very effective in such analysis.

PMID- 22948178
TI  - Design, synthesis and antibacterial activity of minor groove binders: the role of
      non-cationic tail groups.
AB  - The design and synthesis of a new class of minor groove binder (MGBs) in which,
      the cationic tail group has been replaced by a neutral, polar variant including
      cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial
      activity (against Gram positive bacteria) was found for both the nitroalkene and
      trifluoroacetamide groups. For the case of the nitroalkene tail group, strong
      binding of a minor groove binder containing this tail group was demonstrated by
      both DNA footprinting and melting temperature measurements, showing a correlation
      between DNA binding and antibacterial activity. The compounds have also been
      evaluated for binding to the hERG ion channel to determine whether non-cationic
      but polar substituents might have an advantage compared with conventional
      cationic tail groups in avoiding hERG binding. In this series of compounds, it
      was found that whilst non-cationic compounds generally had lower affinity to the
      hERG ion channel, all of the compounds studied bound weakly to the hERG ion
      channel, probably associated with the hydrophobic head groups.

PMID- 22948179
TI  - Sonic hedgehog signaling pathway induces cell migration and invasion through
      focal adhesion kinase/AKT signaling-mediated activation of matrix
      metalloproteinase (MMP)-2 and MMP-9 in liver cancer.
AB  - The aberrant activation of sonic hedgehog (SHH) pathway contributes to initiation
      and progression of various malignancies. However, the roles and underlying
      mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer
      have not been well understood. In this study, we found that SHH signaling was
      activated and correlated with invasion and metastasis in hepatocellular carcinoma
      (HCC). Enhanced SHH signaling by recombinant human SHH N-terminal peptide (rSHH
      N) promoted hepatoma cell adhesion, migration and invasion, whereas blockade of
      SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma
      cell adhesion, migration and invasion. Furthermore, matrix metalloproteinase
      (MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated
      by rSHH-N and SHH signaling inhibitor, respectively. The rSHH-N-mediated hepatoma
      cell migration and invasion was blocked by MMP-specific inhibitors or
      neutralizing antibodies to MMP-2 and MMP-9. In addition, phosphorylations of AKT
      and focal adhesion kinase (FAK) were increased and decreased by rSHH-N and SHH
      signaling inhibitor, respectively. Further investigations showed that activation
      of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9,
      cell migration and invasion. Finally, we found that SHH protein expression was
      positively correlated with phosphorylatd FAK Tyr397, phosphorylatd AKT Ser473,
      MMP-2 and MMP-9 protein expressions in HCC samples. Taken together, our findings
      suggest that SHH pathway induces cell migration and invasion through FAK/AKT
      signaling-mediated MMP-2 and MMP-9 production and activation in liver cancer.

PMID- 22948180
TI  - Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell
      cycle check point and induction of apoptosis.
AB  - Amarogentin, a secoiridoid glycoside, is an active component of the medicinal
      plant Swertia chirata. In this study, chemopreventive and chemotherapeutic
      actions of amarogentin were evaluated in a carbon tetrachloride (CCl(4))/N
      nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during
      continuous and posttreatment schedule. Better survival, no toxicity and increased
      body weight were noted in amarogentin-treated mice. Reduction in proliferation
      and increase in apoptosis frequency were evident in amarogentin-treated groups.
      In carcinogen control group moderate dysplasia, severe dysplasia and
      hepatocellular carcinoma were evident at 10th, 20th and 30th week, respectively.
      Amarogentin was found to prevent progression of liver carcinogenesis at mild
      dysplastic stage. Exposure to CCl(4)/NDEA resulted in upregulation of
      ppRb807/811, cyclinD1 and cdc25A at 10th week and additional activation of cMyc
      and mdm2 along with downregulation of LIMD1, p53 and p21 at 20th week. This was
      followed by activation of ppRb567 and downregulation of Rbsp3 at 30th week.
      Prevention of carcinogenesis by amarogentin in both groups might be due to
      cumulative upregulation of LIMD1, RBSP3, p16 and downregulation of cdc25A at 10th
      week along with activation of p53 and p21 and downregulation of ppRb807/811 and
      ppRb567 at 20th week, followed by downregulation of cyclinD1, cMyc and mdm2 at
      30th week. During carcinogenesis reduction of apoptosis was evident since 20th
      week. However, amarogentin treatment could significantly induce apoptosis through
      upregulation of the Bax-Bcl2 ratio, activation of caspase-3 and poly ADP ribose
      polymerase cleavage. This is the first report of chemopreventive/therapeutic role
      of amarogentin during liver carcinogenesis through modulation of cell cycle and
      apoptosis.

PMID- 22948181
TI  - Experimental and theoretical investigations of the novel ternary compound
      Ca4InGe4.
AB  - A new polar intermetallic compound with a novel structure type has been
      synthesized and characterized by both powder and single-crystal X-ray
      diffraction. Ca(4)InGe(4) crystallizes in the monoclinic crystal system (space
      group C2/c, Z = 4, Pearson symbol mS36) with five crystallographically unique
      atomic positions in the asymmetric unit. The corresponding lattice parameters at
      200(2) K are a = 18.452(8) A, b = 5.819(2) A, c = 8.339(3) A, and beta =
      99.330(6) degrees . The overall crystal structure can be described as a linear
      intergrowth of two imaginary fragments--Ca(2)InGe(2) with the Gd(2)AlGe(2) type-
      and CaGe with the FeB type-structures. Another way to rationalize the bonding is
      to focus on the polyanionic framework, which in this case is made up of unique
      nets of "seesaw"-shaped [InGe(4)] units. They are interconnected via Ge-Ge dimers
      into an open three-dimensional framework with Ca(2+) cations occupying the voids
      within it. Tight-binding linear muffin-tin orbital (LMTO) calculations provide a
      rationale for the unique local coordination geometry around In and the two
      distinct types of Ge-Ge bond distances.

PMID- 22948182
TI  - SPM nanolithography of hydroxy-silicates.
AB  - Bio-nanopatterning of surfaces is becoming a crucial technique with applications
      ranging from molecular and cell biology to medicine. Scanning probe microscopy
      (SPM) is one of the most useful tools for nanopatterning of flat surfaces.
      However, these patterns are usually built on homogeneous surfaces and require
      chemical functionalization to ensure specific affinity. Layered magnesium
      aluminum hydroxide-silicates have already shown unique self-assembly properties
      on DNA molecules, due to their peculiar crystal chemistry based on alternating
      positive and negative crystal layers. However, patterns on these surfaces tend to
      be randomly organized. Here we show etching and oxidation at the nanometer scale
      of magnesium-aluminum hydroxide-silicates using the same SPM probe for the
      creation of organized nanopatterns. In particular, it is possible to produce
      three-dimensional structures in a reproducible way, with a depth resolution of
      0.4 nm, lateral resolution of tens of nm, and a speed of about 10 MUm s(-1). We
      report, as an example, the construction of an atomically flat charged pattern,
      designed to guide DNA deposition along predetermined directions without the need
      of any chemical functionalization of the surface.

PMID- 22948183
TI  - Treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334)
      ameliorates ischemic acute kidney injury.
AB  - BACKGROUND: Hypoxia-inducible factor (HIF) transcriptional system plays a central
      role in cellular adaptation to low oxygen levels. Preconditional activation of
      HIF and/or expression of its individual target gene products leading to
      cytoprotection have been well established in hypoxic/ischemic renal injury.
      Increasing evidence indicate HIF activation is involved in hypoxic/ischemic
      postconditioning of heart, brain and kidney. Very few studies evaluated the
      potential benefits of postischemia HIF activation in renal injury employing a
      pharmacological agent. We hypothesized that postischemia augmentation of HIF
      activation with a pharmacological agent would protect renal ischemia/reperfusion
      injury. For this, TRC160334, a novel HIF hydroxylase inhibitor, was used.
      METHODS: TRC160334, a novel HIF hydroxylase inhibitor, was synthesized. Ability
      of TRC160334 for stabilization of HIF-alpha and consequent HIF activation was
      evaluated in Hep3B cells. Efficacy of TRC160334 was evaluated in a rat model of
      ischemia/reperfusion-induced AKI. Two different treatment protocols were
      employed, one involved treatment with TRC160334 before onset of ischemia, the
      other involved treatment after the reperfusion of kidneys. RESULTS: TRC160334
      treatment results in stabilization of HIF-alpha leading to HIF activation in
      Hep3B cells. Significant reduction in renal injury was observed by both treatment
      protocols and remarkable reduction in serum creatinine (23 and 71% at 24 and 48
      h, respectively, p < 0.01) was observed with TRC160334 treatment applied after
      reperfusion. Urine output was significantly improved up to 24 h by both treatment
      protocols. CONCLUSION: The data presented here provide pharmacologic evidence for
      postischemia augmentation of HIF activation by TRC160334 as a promising and
      clinically feasible strategy for the treatment of renal ischemia/reperfusion
      injury.

PMID- 22948184
TI  - Defining care provided for breast cancer based on medical record review or
      Medicare claims: information from the Centers for Disease Control and Prevention
      Patterns of Care Study.
AB  - BACKGROUND: Description of care patterns is important as evidence-based
      guidelines increasingly dictate care. We explore the level of agreement between
      claims and record abstraction for guideline concordant multidisciplinary breast
      cancer care. METHODS: From the U.S. Centers for Disease Control and Prevention's
      National Program of Cancer Registries Patterns of Care study, in which medical
      record abstraction of breast cancer and treatment was accomplished, cases include
      breast cancer where Medicare claims were available. Components of care were
      breast-conserving surgery (BCS), mastectomy, node assessment, radiation (RT), and
      chemotherapy (CTX), including specific chemotherapeutic agents, and combinations.
      We compared Medicare claims with record abstraction, and measured concordance
      using the kappa statistic and sensitivity. RESULTS: The study sample consisted of
      1762 women with stage 0 to 4 breast cancer. Level of agreement was excellent for
      surgery type (kappa = 0.84) and CTX (kappa = 0.89); agreement for RT therapy was
      slightly lower (kappa = 0.79). For standard multicomponent strategies,
      sensitivities and specificities were high; for example, 88.8%/93.5% for
      mastectomy plus nodes and 86.6%/95.4% for BCS plus nodes and RT. For selected,
      standard, multi-agent, adjuvant CTX regimens, sensitivities ranged from 66.3% to
      68.8% (kappa 0.63-0.73). CONCLUSIONS: Medicare claims, compared with chart
      abstraction, is a reliable method for determining patterns of multicomponent care
      for breast cancer.

PMID- 22948185
TI  - The neural adhesion molecule L1CAM confers chemoresistance in human
      glioblastomas.
AB  - Glioblastoma multiforme (GBM) represents the most common and malignant brain
      tumor. GBM tissues exhibit elevated expression of the transforming growth factor
      beta1 (TGF-beta1) and the adhesion molecule L1CAM. This study investigated the
      mechanism of L1CAM regulation in GBM cells and its role in the mediation of
      chemoresistance. L1CAM expression levels varied in GBM cells being highest in
      A172 cells and low in T98G cells. Inhibition of TGF-beta1 signaling in A172 cells
      reduced L1CAM expression and vice versa stimulation with exogenous TGF-beta1 led
      to upregulation of L1CAM in T98G cells. Additionally, TGF-beta1 and L1CAM
      expression increased during differentiation of glioma stem-like cells. L1CAM
      expressing GBM cells and differentiated glioma stem-like cells showed a reduced
      apoptotic response after treatment with the chemotherapeutic drug temozolomide.
      Accordingly, siRNA-mediated knock-down of L1CAM in A172 cells and differentiated
      glioma stem-like cells increased chemosensitivity, whereas overexpression of
      L1CAM in T98G cells and glioma spheroids diminished the apoptotic response.
      Elevated L1CAM expression caused a diminished expression of caspase-8 in GBM and
      differentiated glioma stem-like cells. These data show that TGF-beta1 dependent
      upregulation of L1CAM expression in GBM cells leads to the downregulation of
      caspase-8 and apoptosis resistance pointing to L1CAM as potential target for
      improved therapy of GBM patients.

PMID- 22948186
TI  - Effective population size in eusocial Hymenoptera with worker-produced males.
AB  - In many eusocial Hymenoptera, a proportion of males are produced by workers. To
      assess the effect of male production by workers on the effective population size
      N(e), a general expression of N(e) in Hymenoptera with worker-produced males is
      derived on the basis of the genetic drift in the frequency of a neutral allele.
      Stochastic simulation verifies that the obtained expression gives a good
      prediction of N(e) under a wide range of conditions. Numerical computation with
      the expression indicates that worker reproduction generally reduces N(e). The
      reduction can be serious in populations with a unity or female-biased breeding
      sex ratio. Worker reproduction may increase N(e) in populations with a male
      biased breeding sex ratio, only if each laying worker produce a small number of
      males and the difference of male progeny number among workers is not large.
      Worker reproduction could be an important cause of the generally lower genetic
      variation found in Hymenoptera, through its effect on N(e).

PMID- 22948187
TI  - Measuring linkage disequilibrium by the partial correlation coefficient.

PMID- 22948188
TI  - Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7
      with pyrethroid resistance in the malaria vector Anopheles funestus.
AB  - Pyrethroid resistance in Anopheles funestus is threatening malaria control in
      Africa. Elucidation of underlying resistance mechanisms is crucial to improve the
      success of future control programs. A positional cloning approach was used to
      identify genes conferring resistance in the uncharacterised rp2 quantitative
      trait locus (QTL) previously detected in this vector using F6 advanced intercross
      lines (AIL). A 113 kb BAC clone spanning rp2 was identified and sequenced
      revealing a cluster of 15 P450 genes and one salivary protein gene (SG7-2).
      Contrary to A. gambiae, AfCYP6M1 is triplicated in A. funestus, while AgCYP6Z2
      orthologue is absent. Five hundred and sixty-five new single nucleotide
      polymorphisms (SNPs) were identified for genetic mapping from rp2 P450s and other
      genes revealing high genetic polymorphisms with one SNP every 36 bp. A
      significant genotype/phenotype association was detected for rp2 P450s but not for
      a cluster of cuticular protein genes previously associated with resistance in A.
      gambiae. QTL mapping using F6 AIL confirms the rp2 QTL with an increase logarithm
      of odds score of 5. Multiplex gene expression profiling of 15 P450s and other
      genes around rp2 followed by individual validation using qRT-PCR indicated a
      significant overexpression in the resistant FUMOZ-R strain of the P450s AfCYP6Z1,
      AfCYP6Z3, AfCYP6M7 and the glutathione-s-transferase GSTe2 with respective fold
      change of 11.2, 6.3, 5.5 and 2.8. Polymorphisms analysis of AfCYP6Z1 and AfCYP6Z3
      identified amino acid changes potentially associated with resistance further
      indicating that these genes are controlling the pyrethroid resistance explained
      by the rp2 QTL. The characterisation of this rp2 QTL significantly improves our
      understanding of resistance mechanisms in A. funestus.

PMID- 22948189
TI  - Comparison of catheter-related large vein thrombosis in centrally inserted versus
      peripherally inserted central venous lines in the neurological intensive care
      unit.
AB  - OBJECTIVE: To compare cumulative complication rates of peripherally (PICC) and
      centrally (CICVC) inserted central venous catheters, including catheter-related
      large vein thrombosis (CRLVT), central line-associated bloodstream infection
      (CLABSI), and line insertion-related complications in neurological intensive care
      patients. METHODS: Retrospective cohort study and detailed chart review for 431
      consecutive PICCs and 141 CICVCs placed in patients under neurological intensive
      care from March 2008 through February 2010. Cumulative incidence of CRLVT,
      CLABSI, and line insertion-related complications were compared between PICC and
      CICVC groups. Risk factors for CRLVT including mannitol therapy during dwell
      time, previous history of venous thromboembolism, surgery longer than 1h during
      dwell time, and line placement in a paretic arm were also compared between
      groups. RESULTS: During the study period, 431 unique PICCs were placed with
      cumulative incidence of symptomatic thrombosis of 8.4%, CLABSI 2.8%, and line
      insertion-related complications 0.0%. During the same period, 141 unique CICVCs
      were placed with cumulative incidence of symptomatic thrombosis of 1.4%, CLABSI
      1.4%, and line insertion-related complications 0.7%. There was a statistically
      significant difference in CRLVT with no difference in CLABSI or line insertion
      related complications. CONCLUSIONS: In neurological critical care patients,
      CICVCs appear to have a better risk profile compared to PICCs, with a decreased
      risk of CRLVT. As use of PICCs in critical care patients increases, a prospective
      randomized trial comparing PICCs and CICVCs in neurological critical care
      patients is necessary to assist in choosing the appropriate catheter and to
      minimize risks of morbidity and mortality associated with central venous access.

PMID- 22948190
TI  - Novel use of bone cement to aid atlanto-axial distraction in the treatment of
      basilar invagination: a case report and technical note.

PMID- 22948191
TI  - Flexible and tenacious goal pursuit lead to improving well-being in an aging
      population: a ten-year cohort study.
AB  - BACKGROUND: Previous research has shown that tendencies to tenaciously pursue
      goals and flexibly adapt goals independently relate to well-being in adults in
      mid-to-late life, but research has not tested whether these tendencies interact.
      For example, tenacity may only predict well-being in combination with
      flexibility. This research tests whether these tendencies interact to predict
      changes in health-related outcomes. METHODS: A large cohort of people (n =
      5,666), initially aged 55-56, completed measures of flexibility, tenacity, health
      related outcomes (physical health, depression, hostility), as well as
      demographics. Participants provided follow-up data on all measures ten years
      later. Moderation analysis was used to test whether flexibility and tenacity
      interacted to predict changes in the health-related outcomes over the period.
      RESULTS: The interaction between tenacity and flexibility significantly predicted
      changes in depression, hostility, and physical ill-health symptoms over ten
      years, such that highly flexible and tenacious individuals experienced the
      largest decreases in symptoms of depression, hostility, and physical ill-health.
      CONCLUSIONS: The interaction between flexibility and tenacity predicts greater
      well-being, such that one is most protective when an individual also scores
      highly on the other. The combination of flexibility and tenacity in the pursuit
      of personal goals may mean individuals can enjoy gains associated with goal
      pursuit without the detrimental effects of persevering in blocked goals.

PMID- 22948192
TI  - Non-contact respiration monitoring for in-vivo murine micro computed tomography:
      characterization and imaging applications.
AB  - A cone beam micro-CT has previously been utilized along with a pressure-tracking
      respiration sensor to acquire prospectively gated images of both wild-type mice
      and various adult murine disease models. While the pressure applied to the
      abdomen of the subject by this sensor is small and is generally without
      physiological effect, certain disease models of interest, as well as very young
      animals, are prone to atelectasis with added pressure, or they generate too weak
      a respiration signal with this method to achieve optimal prospective gating. In
      this work we present a new fibre-optic displacement sensor which monitors
      respiratory motion of a subject without requiring physical contact. The sensor
      outputs an analogue signal which can be used for prospective respiration gating
      in micro-CT imaging. The device was characterized and compared against a
      pneumatic air chamber pressure sensor for the imaging of adult wild-type mice.
      The resulting images were found to be of similar quality with respect to
      physiological motion blur; the quality of the respiration signal trace obtained
      using the non-contact sensor was comparable to that of the pressure sensor and
      was superior for gating purposes due to its better signal-to-noise ratio. The non
      contact sensor was then used to acquire in-vivo micro-CT images of a murine model
      for congenital diaphragmatic hernia and of 11-day-old mouse pups. In both cases,
      quality CT images were successfully acquired using this new respiration sensor.
      Despite the presence of beam hardening artefacts arising from the presence of a
      fibre-optic cable in the imaging field, we believe this new technique for
      respiration monitoring and gating presents an opportunity for in-vivo imaging of
      disease models which were previously considered too delicate for established
      animal handling methods.

PMID- 22948193
TI  - Electron beam induced deposition of silicon nanostructures from a liquid phase
      precursor.
AB  - This work demonstrates electron beam induced deposition of silicon from a SiCl(4)
      liquid precursor in a transmission electron microscope and a scanning electron
      microscope. Silicon nanodots of tunable size are reproducibly grown in controlled
      geometries. The volume of these features increases linearly with deposition time.
      The results indicate that secondary electrons generated at the substrate surface
      serve as the primary source of silicon reduction. However, at high current
      densities the influence of the primary electrons is observed to retard growth.
      The results demonstrate a new approach to fabricating silicon nanostructures and
      provide fundamental insights into the mechanism for liquid phase electron beam
      induced deposition.

PMID- 22948194
TI  - Retrospective analysis of nodal spread patterns according to tumor location in
      pathological N2 non-small cell lung cancer.
AB  - BACKGROUND: The purpose of the present study was to determine the nodal spread
      patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location,
      and to attempt to evaluate the possible indications of selective lymph node
      dissection (SLND). METHODS: We retrospectively analyzed nodal spread patterns in
      207 patients with NSCLC of less than 5 cm with N2 involvement. RESULTS: The tumor
      location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe
      (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left
      lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of
      upper mediastinal (UM) involvement (96 and 100%, respectively) and a lower
      incidence of subcarinal involvement (15 and 10%, respectively) than lower lobe
      tumors (UM; RLL 60%, LLL 42%; subcarinal: RLL 60%, LLL 46%, respectively). Among
      the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2
      showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1,
      suggesting that UM dissection may be unnecessary in lower lobe tumors with no
      metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections
      according to the preoperative T status. Among the patients with 12 subcarinal
      positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or
      UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL
      or LUD tumors with no metastasis to hilar and UM nodes on frozen sections.
      CONCLUSIONS: The present study appears to provide one of the supportive results
      regarding the treatment strategies for tumor location-specific SLND.

PMID- 22948195
TI  - Examining a common disease with unknown etiology: trends in epidemiology and
      surgical management of appendicitis in California, 1995-2009.
AB  - BACKGROUND: The study was designed to examine the epidemiology of appendicitis
      and risk factors of perforation and appendectomy. METHODS: Retrospective analysis
      of the California Office of Statewide Health Planning and Development Patient
      Discharge Data was performed from 1995 to 2009. Patients with appendicitis were
      identified by ICD-9 diagnosis code. Population statistics from the RAND
      Corporation were used to calculate incidence rates. Risk factors of perforation
      and appendectomy were also calculated. RESULTS: A total of 608,116 patients with
      appendicitis (70% non-perforated) were included. The incidence increased at an
      average rate of 0.5 cases/100,000 population/year (p<0.001), with annual
      incidence peaking during the third quarter. Children age 10-14 had the highest
      rates of appendicitis (169.6 cases/100,000). The lifetime cumulative incidence
      rate is 9.0%. Appendicitis is most common in whites and Hispanics and less common
      in African Americans and Asians. Risks of perforation include Hispanic or Asian
      race, young or old age, and non-private insurance. The adjusted odds of
      appendectomy increased since 1995 in patients with non-perforated appendicitis
      (OR 1.5, 95% CI (1.3-1.7); p<0.001), but it decreased in patients with perforated
      appendicitis (OR 0.4, 95% CI (0.4-0.5); p<0.001). CONCLUSIONS: This is the
      largest epidemiological study of appendicitis to our knowledge in recent years.
      Incidence has increased over time and is higher in the summer months. Whites and
      Hispanics have higher rates of appendicitis, but Hispanics and Asians and
      patients with non-private insurance, have higher odds of perforation. Surgical
      management of perforated appendicitis has decreased over time. It is unknown why
      the incidence has increased, displays seasonality, and varies by race.

PMID- 22948196
TI  - Changes in body composition, hematologic parameters, and serum biochemistry after
      rapid intravenous infusion or oral intake of 2 liters of 0.9% saline solution in
      young healthy volunteers: randomized crossover study.
AB  - BACKGROUND: The perioperative infusion of 2 L of saline is associated with weight
      gain and decreased serum albumin and hematocrit. We hypothesized that these
      parameters would respond differently to oral administration and intravenous
      infusion of saline solution. METHODS: This was a crossover study that included 10
      healthy young men (ages 18-26 years). At two times, 8 weeks apart, the
      participants were randomized to receive 2 L of 0.9% saline over 1 h by
      intravenous (IV) administration to a forearm vein or by oral intake. The
      participants were weighed and body masses were calculated. Bioelectrical
      impedance analysis was performed with a single-frequency device using tetrapolar
      distal limb electrodes. Blood samples were collected 1 h after the administration
      period for laboratory assays: hematocrit, hemoglobin, blood glucose, serum
      electrolytes, albumin, creatinine, osmolality. RESULTS: There was an increase in
      body weight (p<0.01), total body water (p<0.01), and lean body mass (p<0.01)
      after the experiment in both groups, with no difference between them. The volume
      of urine output was similar in the two experiments. The hemoglobin (oral group
      from 14.4+/-0.8 g/dl to 13.8+/-0.8 g/dl; IV group from 14.4+/-0.6 g/dl to 12.6+/
      0.6 g/dl) and hematocrit (oral group from 43.2+/-1.8% to 43.2+/-2.8%; IV group
      from 43.6+/-2.2% to 40.0+/-2.6%) significantly decreased (p<0.01) with IV saline.
      Serum albumin remained stable after oral intake but significantly decreased
      (p=0.04) after IV infusion. CONCLUSIONS: Oral intake of 2 L of 0.9% saline
      results in minimal variations in serum albumin, hemoglobin, and hematocrit when
      compared to IV infusion of the same volume.

PMID- 22948197
TI  - Low perioperative serum prealbumin predicts early recurrence after curative
      pulmonary resection for non-small-cell lung cancer.
AB  - BACKGROUND: Early recurrence after surgery for non-small-cell lung cancer (NSCLC)
      is often observed in spite of pathologically proven early-stage disease. The aim
      of this study was to identify biomarkers that might be useful in predicting
      postoperative early recurrence of lung cancer. In this study we evaluated the
      perioperative nutritional status of the patients by measuring the serum level of
      prealbumin and analyzed the correlation between this factor and early recurrence.
      METHODS: Forty-four patients with NSCLC were enrolled in the study. Serum level
      of prealbumin was measured 5 days before and 7 days after surgery, respectively.
      RESULTS: For the patients who developed early recurrence, the perioperative serum
      prealbumin level was statistically significantly lower than those of the patients
      who did not develop recurrence (p<0.05). Furthermore, the patients with low
      prealbumin level showed statistically significantly poorer outcomes compared with
      the patients with higher prealbumin level (p<0.001). On the other hand, there was
      no correlation between the pathological stage and the serum prealbumin level.
      Multivariate analysis revealed that low perioperative serum prealbumin level
      could be an independent prognostic factor of poor outcome (hazard ratio, 10.1;
      95% confidence interval, 2.8-35.5; p=0.0003). CONCLUSIONS: Low serum prealbumin
      level in the perioperative period is associated with a poorer prognosis in NSCLC
      patients and could serve as a marker for identifying patients at high risk, even
      at an early clinical stage.

PMID- 22948198
TI  - Stent-assisted coil embolization and computational fluid dynamics simulations of
      bilateral vertebral artery dissecting aneurysms presenting with subarachnoid
      hemorrhage:  case report.
AB  - BACKGROUND AND IMPORTANCE: A vertebral artery dissecting aneurysm (VADA) is a
      relatively rare cause of subarachnoid hemorrhage. Bilateral VADAs are even rarer,
      and management strategies are controversial. We report a case of bilateral VADAs
      presenting with subarachnoid hemorrhage. We treated the patient by stent-assisted
      coil embolization of both aneurysms at a single session on the basis of results
      of preoperative computational fluid dynamic simulations. CLINICAL PRESENTATION: A
      48-year-old man presented with subarachnoid hemorrhage resulting from bilateral
      VADAs. We treated the patient by stent-assisted coil embolization of both
      aneurysms at a single session. Before the treatment, we performed computational
      fluid dynamics simulations to predict the ruptured side. We also estimated the
      increase in wall shear stress on an aneurysm in case of trapping of another
      aneurysm, which might cause enlargement and rupture of the aneurysm. The
      treatment was performed successfully. The patient remains neurologically intact
      at 14 months from the onset. CONCLUSION: Stent-assisted coil embolization of
      subarachnoid hemorrhage with bilateral VADAs for both sides is a reasonable
      treatment because it prevents rebleeding and preserves bilateral vertebral
      arteries without increasing hemodynamic stress. To the best of our knowledge,
      this is the first report to describe this type of treatment for bilateral VADAs
      with subarachnoid hemorrhage. Computational fluid dynamics simulations may be
      useful for developing treatment strategies for aneurysms.

PMID- 22948199
TI  - Early postmarket results after treatment of intracranial aneurysms with the
      pipeline embolization device: a U.S. multicenter experience.
AB  - BACKGROUND: The pipeline embolization device (PED) is the latest technology
      available for intracranial aneurysm treatment. OBJECTIVE: To report early
      postmarket results with the PED. METHODS: This study was a prospective registry
      of patients treated with PEDs at 7 American neurosurgical centers subsequent to
      Food and Drug Administration approval of this device. Data collected included
      clinical presentation, aneurysm characteristics, treatment details, and
      periprocedural events. Follow-up data included degree of aneurysm occlusion and
      delayed (> 30 days after the procedure) complications. RESULTS: Sixty-two PED
      procedures were performed to treat 58 aneurysms in 56 patients. Thirty-seven of
      the aneurysms (64%) treated were located from the cavernous to the superior
      hypophyseal artery segment of the internal carotid artery; 22% were distal to
      that segment, and 14% were in the vertebrobasilar system. A total of 123 PEDs
      were deployed with an average of 2 implanted per aneurysm treated. Six devices
      were incompletely deployed; in these cases, rescue balloon angioplasty was
      required. Six periprocedural (during the procedure/within 30 days after the
      procedure) thromboembolic events occurred, of which 5 were in patients with
      vertebrobasilar aneurysms. There were 4 fatal postprocedural hemorrhages (from 2
      giant basilar trunk and 2 large ophthalmic artery aneurysms). The major
      complication rate (permanent disability/death resulting from
      perioperative/delayed complication) was 8.5%. Among 19 patients with 3-month
      follow-up angiography, 68% (13 patients) had complete aneurysm occlusion. Two
      patients presented with delayed flow-limiting in-stent stenosis that was
      successfully treated with angioplasty. CONCLUSION: Unlike conventional coil
      embolization, aneurysm occlusion with PED is not immediate. Early complications
      include both thromboembolic and hemorrhagic events and appear to be significantly
      more frequent in association with treatment of vertebrobasilar aneurysms.

PMID- 22948200
TI  - Lateral extracavitary vs. costotransversectomy approaches to the thoracic spine:
      reflections on lessons learned.
AB  - BACKGROUND: The lateral extracavitary approach (LECA) and costotransversectomy
      (CTE) are 2 dorsolateral approaches that avoid entrance into the pleural cavity
      and facilitate ventral decompression. The indications and outcomes of each of
      these approaches have not been fully defined in the literature. OBJECTIVE: To
      assess the techniques, indications, and complications associated with the LECA
      and CTE approaches to the thoracic spine. METHODS: A retrospective analysis was
      performed on all patients who underwent LECA and CTE between 2000 and 2009 at our
      institution. RESULTS: A total of 54 patient charts were reviewed (19 LECA, 35
      CTE). Indications for operation included disk herniation, trauma, tumor,
      osteomyelitis, and scoliosis/kyphosis. Osteomyelitis was treated significantly
      more often with LECA (47%) than with CTE (9%; P = .002). Mean blood loss was 2134
      mL and 1556 mL (P = .3) in LECA and CTE, respectively, and hospital stay was 17.2
      days for LECA and 9.8 days for CTE (P = .07). Thirteen LECA patients (68%) and 19
      CTE patients (54%; P = 1.0) had preoperative or postoperative complications.
      CONCLUSION: LECA was used more often to treat complex pathologies such as
      osteomyelitis and trended toward significance for more frequent use in extensive
      procedures involving 1- or 2-level corpectomies. As can be expected, CTE was
      associated with slightly less blood loss and a shorter hospital stay compared
      with the more extensive LECA operation. Adverse outcomes occurred with similar
      frequency for CTE and LECA.

PMID- 22948201
TI  - The anatomical and electrophysiological subthalamic nucleus visualized by 3-T
      magnetic resonance imaging.
AB  - BACKGROUND: Accurate localization of the subthalamic nucleus (STN) is critical to
      the success of deep brain stimulation surgery for Parkinson disease. Recent
      developments in high-field-strength magnetic resonance imaging (MRI) have made it
      possible to visualize the STN in greater detail. However, the relationship of the
      MR-visualized STN to the anatomic, electrophysiological, or atlas-predicted STN
      remains controversial. OBJECTIVE: To evaluate the size of the STN visualized on 3
      T MRI compared with anatomic measurements in cadaver studies and to compare the
      predictions of 3-T MRI and those of the Schaltenbrand-Wahren (SW) atlas for
      intraoperative STN microelectrode recordings. METHODS: We evaluated the STN by 3
      T MRI and intraoperative microelectrode recordings in 20 Parkinson disease
      patients undergoing deep brain stimulation surgery. We compared our findings with
      anatomic cadaver studies and with the individually scaled SW atlas-based
      predictions for each patient. RESULTS: The dimensions of the 3-T MR-visualized
      STN were very similar to those of the largest anatomic study (MRI length, width,
      and height: 9.8 +/- 1.6, 11.5 +/- 1.6, and 3.7 +/- 0.7 mm, respectively; n = 40;
      cadaver length, width, and height: 9.3 +/- 0.7, 10.6 +/- 0.9, and 3.1 +/- 0.5 mm,
      respectively; n = 100). The amount of STN traversed during intraoperative
      microelectrode recordings was better correlated to the 3-T MR-visualized STN than
      the SW atlas-predicted STN (R = 0.38 vs R = -0.17). CONCLUSION: The STN as
      visualized on 3-T MRI corresponds well with cadaveric anatomic studies and
      intraoperative electrophysiology. STN visualization with 3-T MRI may be an
      improvement over SW atlas-based localization for STN deep brain stimulation
      surgery in Parkinson disease.

PMID- 22948202
TI  - Working memory and speed of information processing in chronic khat users:
      preliminary findings.
AB  - To date there are very few laboratory data available regarding the long-term
      effect of the psychostimulant khat on human neurocognitive functioning. The
      purpose of the present study was to assess whether chronic khat users would
      demonstrate impairments in working memory and speed of information processing
      compared to control subjects. Working memory was assessed using the forward and
      backward digit span test. Speed of information processing was assessed using the
      Digit Symbol Substitution Test. Results of the present study indicate that
      chronic khat use may have a long-term deleterious effect on working memory,
      particularly on digit backwards measures of short-term/working memory. The
      finding is consistent with results seen by several investigators in samples of
      methamphetamine users.

PMID- 22948203
TI  - Anaphylactic versus mild reactions to hazelnut and apple in a birch-endemic area:
      different sensitization profiles?.
AB  - BACKGROUND: Hazelnut and apple are common causes of food allergy in Europe. In
      northern Europe, symptoms are usually mild and associated with cross-reactivity
      to the birch pollen allergen, Bet v 1. In the Mediterranean area, symptoms are
      more frequently severe and associated with sensitization to lipid transfer
      protein (LTP). This study compared patients with anaphylactic versus mild
      reactions to hazelnut and apple in The Netherlands, a birch-endemic area, with
      respect to sensitization to Bet v 1-homologues (i.e. PR10-proteins) and LTP.
      METHODS: Twenty-one patients fulfilling the criteria for anaphylaxis and 21 with
      only mild symptoms (oral allergy) to hazelnut and/or apple were recruited.
      Specific immunoglobulin E to birch pollen, apple, hazelnut and PR10-proteins
      (rBet v 1, rPru p 1, rMal d 1 and rCor a 1) and recombinant LTP (rPru p 3 and
      rCor a 8) was measured by ImmunoCAP. RESULTS: Both mild and anaphylactic apple
      allergic patients were sensitized to PR10-proteins, whereas only 1/7 of the mild
      and none of the anaphylactic apple-allergic patients was sensitized to LTP. In
      contrast, anaphylactic hazelnut-allergic patients displayed no such clear
      sensitization pattern: some were sensitized to both PR10-proteins and hazelnut
      LTP (1/9), and others to only LTP (2/9) or to only PR10-proteins (4/9) or to
      neither PR10-proteins nor LTP (2/9). CONCLUSION: This study shows that in a birch
      endemic area, the sensitization profile to PR10-proteins and LTP in anaphylactic
      patients may differ between different plant foods. In this patient group,
      anaphylaxis to hazelnut can be LTP-associated, whereas anaphylaxis to apple is
      not.

PMID- 22948204
TI  - Heat shock pretreatment reduces intestinal injury in a neonatal rat model of
      early necrotizing enterocolitis.
AB  - BACKGROUND: Increased pro-inflammatory cytokines are suggested in the
      pathogenesis of necrotizing enterocolitis (NEC). The transcription factor,
      nuclear factor-KB (NF-KB), is a central regulator of inflammatory and immune
      responses, and recent rodent NEC models have shown that NF-KB may have a critical
      role in the disease processes that underlie NEC. Heat shock proteins have
      important functions in response to stress-related events in a variety of systems,
      including digestive organs. OBJECTIVES: We investigated whether heat shock
      pretreatment protects intestinal epithelial damage in the early NEC rat model.
      METHODS: We generated human NEC-like lesions in neonatal rat ileum by
      administering oral endotoxin (10 mg/kg), intermittent 8% hypoxia, and hypertonic
      formula. Heat shock was administered by raising the chamber temperature to 42
      degrees C for 20 min, 3 h prior to endotoxin ingestion. RESULTS: Heat shock
      pretreatment increased the expression of HSP70 in the ileal tissue and attenuated
      histological severity of early experimental NEC. NF-KB was activated in the ileal
      tissue of the NEC group and this activation was attenuated by heat shock
      pretreatment, which was determined by electrophoretic mobility shift assay and
      Western blot analysis of p50 in subcellular fractionated samples. CONCLUSIONS:
      Heat shock pretreatment reduced the incidence and severity of early experimental
      NEC in rats. A possible mechanism underlying this protective effect includes
      inhibition of NF-KB activation through increased HSP70 expression.

PMID- 22948205
TI  - Genetic variability of Blastocystis sp. isolated from symptomatic and
      asymptomatic individuals in Iran.
AB  - Blastocystis is an unusual enteric protozoan parasite of humans and many animals
      whose pathogenic potential is still controversial. To increase the understanding
      of the molecular epidemiology of this emerging parasite and due to its potential
      impact on public health, its subtypes (STs) in Iranian symptomatic and
      asymptomatic individuals were determined. A total of 100 Blastocystis isolates by
      microscopy and culture methods were obtained. DNA was extracted from the positive
      culture isolates, and the Blastocystis subtypes were identified using seven
      subtype-specific sequenced-tagged site (STS) primers. Four subtypes, ST3 as
      dominant (53 %), followed by ST1 (48 %), ST5 (33 %), and ST2 (7 %) were
      identified. In this study, ST1 in gastrointestinal patients compared to
      asymptomatic individuals was significantly dominant (p = 0.001). From 33 (33 %)
      mixed subtype infections, ST1, 3 (14 %) was significantly related to GI symptoms
      (p = 0.045), and eight mixed infections with three different STs, which are under
      reported, were also identified.

PMID- 22948206
TI  - Further indication of lowered activity of ivermectin on immature small strongyles
      in the intestinal lumen of horses on a farm in Central Kentucky.
AB  - Critical tests were performed in 2011 in four weanling horses (L-1, L-2, L-29,
      and L-30) treated with ivermectin paste at 200 MUg/kg. They were born in 2011 and
      raised together on a farm (MC) in Central Kentucky. The horses had not been
      treated previously with an antiparasitic drug. However, ivermectin had been
      administered repeatedly to the horse herd for several years and strongyle eggs
      per gram of feces (EPGs) returned sooner posttreatment than after initial usage.
      Critical tests in a recent previous study in this horse herd indicated that the
      reason for the early return of strongyle EPGs after ivermectin treatment probably
      was because of lowered drug activity on immature (L(4)) small strongyles in the
      lumen of the large intestine. Therefore, the life cycle was shortened. The main
      purpose of the present study was to obtain further data on the activity of
      ivermectin on small strongyle immature stages, in addition to adults, in the
      intestinal lumen. Twelve species of small strongyles were present. Combined data
      for immature and adult small strongyles for the four ivermectin-treated horses
      demonstrated efficacy of 68 to 83 %. Removal of adults was 100 % for all four
      horses, and on immatures, it ranged from 0 to 16 %. Efficacy on immature small
      strongyles was even lower than in the previous study. This supported the earlier
      finding of apparent reduced time for maturation of the parasites because of
      incomplete elimination of immature small strongyles in the intestinal lumen of
      horses after ivermectin treatment. Data on five other helminth species were
      recorded.

PMID- 22948207
TI  - Heat localization for targeted tumor treatment with nanoscale near-infrared
      radiation absorbers.
AB  - Focusing heat delivery while minimizing collateral damage to normal tissues is
      essential for successful nanoparticle-mediated laser-induced thermal cancer
      therapy. We present thermal maps obtained via magnetic resonance imaging
      characterizing laser heating of a phantom tissue containing a multiwalled carbon
      nanotube inclusion. The data demonstrate that heating continuously over tens of
      seconds leads to poor localization (~ 0.5 cm) of the elevated temperature region.
      By contrast, for the same energy input, heat localization can be reduced to the
      millimeter rather than centimeter range by increasing the laser power and
      shortening the pulse duration. The experimental data can be well understood
      within a simple diffusive heat conduction model. Analysis of the model indicates
      that to achieve 1 mm or better resolution, heating pulses of ~2 s or less need to
      be used with appropriately higher heating power. Modeling these data using a
      diffusive heat conduction analysis predicts parameters for optimal targeted
      delivery of heat for ablative therapy.

PMID- 22948209
TI  - Dental age of children and adolescents with impacted maxillary canines.
AB  - INTRODUCTION: It is generally perceived that patients with palatally impacted
      canines experience a delay in dental development, while patients with buccally
      impacted canines do not. Nevertheless, there is little scientific data on the
      subject, and no data at all on Chinese populations. The objectives of this study
      were, thus, to determine whether patients with impacted canines would demonstrate
      delayed dental development. DESIGN: Retrospective radiographic study. SETTING:
      Dental hospital. METHODS: Our study enrolled southern Chinese children and
      adolescents with unilaterally impacted maxillary canines. A total of 281
      panoramic radiographs were available to assess dental age. Demirjian's method was
      utilized to determine the dental age. RESULTS: The discrepancy between dental and
      chronologic ages was then calculated, revealing a mean difference of 0.4 years
      (+/- 0.2 years), indicating advanced dental development. The cumulative
      difference between dental age and chronologic age showed that 42.2% of the
      patients with a buccally impacted canine and 30% with a palatally impacted canine
      experienced a delay in dental development, or coincided with their chronologic
      age. CONCLUSION: Less than half of the patients with both buccally and palatally
      impacted canines showed delayed dental development. Their dental maturity was on
      average slightly but clinically insignificantly advanced.

PMID- 22948210
TI  - Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY
      neuron neuropeptides in female mice.
AB  - Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons act to
      sense and coordinate the brain's responses to metabolic cues. One neuronal
      network that is very sensitive to metabolic status is that controlling fertility.
      In this study, we investigated the impact of neuropeptides released by NPY and
      POMC neurons on the cellular excitability of GnRH neurons, the final output cells
      of the brain controlling fertility. The majority (~70%) of GnRH neurons were
      activated by alpha-melanocyte-stimulating hormone, and this resulted from the
      direct postsynaptic activation of melanocortin receptor 3 and melanocortin
      receptor 4. A small population of GnRH neurons (~15%) was excited by cocaine and
      amphetamine-regulated transcript or inhibited by beta-endorphin. Agouti-related
      peptide, released by NPY neurons, was found to have variable inhibitory (~10%)
      and stimulatory (~25%) effects upon subpopulations of GnRH neurons. A variety of
      NPY and pancreatic polypeptide analogs was used to examine potential NPY
      interactions with GnRH neurons. Although porcine NPY (Y1/Y2/Y5 agonist) directly
      inhibited the firing of approximately 45% of GnRH neurons, [Leu(31),Pro(34)]-NPY
      (Y1/Y4/Y5 agonist) could excite (56%) or inhibit (19%). Experiments with further
      agonists indicated that Y1 receptors were responsible for suppressing GnRH neuron
      activity, whereas postsynaptic Y4 receptors were stimulatory. These results show
      that the activity of GnRH neurons is regulated in a complex manner by
      neuropeptides released by POMC and NPY neurons. This provides a direct route
      through which different metabolic cues can regulate fertility.

PMID- 22948211
TI  - Growth hormone secretagogues preserve the electrophysiological properties of
      mouse cardiomyocytes isolated from in vitro ischemia/reperfusion heart.
AB  - Ischemic heart diseases often induce cardiac arrhythmia with irregular cardiac
      action potential (AP). This study aims to demonstrate that GH secretagogues (GHS)
      ghrelin and its synthetic analog hexarelin can preserve the electrophysiological
      properties of cardiomyocytes experiencing ischemia/reperfusion (I/R). Isolated
      hearts from adult male mice underwent 20 min global ischemia followed by 30 min
      reperfusion using a Langendorff apparatus. Ghrelin (10 nM) or hexarelin (1 nM)
      was administered in the perfusion solution either 10 min before or after
      ischemia, termed pre- or posttreatments. Cardiomyocytes isolated from these
      hearts were used for whole-cell patch clamping to measure AP, voltage-gated L
      type calcium current (I(CaL)), transient outward potassium current (I(to)), and
      sodium current (I(Na)). AP amplitude and duration were significantly decreased by
      I/R, but GHS treatments maintained their normality. GHS treatments prevented the
      decrease in I(CaL) and I(Na) after I/R, thereby maintaining AP amplitude.
      Although the significant increase in I(to) after I/R partially explained the
      shortened AP duration, the normalization of it by GHS treatments might contribute
      to the preservation of AP duration. Phosphorylated p38 and c-Jun NH(2)-terminal
      kinase and the downstream active caspase-9 in the cellular apoptosis pathway were
      significantly increased after I/R but not when GHS treatments were included,
      whereas phosphorylation of ERK1/2 associated with cell survival showed increase
      after I/R and a further increase after GHS treatments by binding to its receptor
      GHS receptor type 1a. These results suggest GHS can not only preserve the
      electrophysiological properties of cardiomyocytes after I/R but also inhibit
      cardiomyocyte apoptosis and promote cell survival by modification of MAPK
      pathways through activating GHS receptor type 1a.

PMID- 22948212
TI  - Thyroid hormone reduces cholesterol via a non-LDL receptor-mediated pathway.
AB  - Although studies in vitro and in hypothyroid animals show that thyroid hormone
      can, under some circumstances, modulate the actions of low-density lipoprotein
      (LDL) receptors, the mechanisms responsible for thyroid hormone's lipid-lowering
      effects are not completely understood. We tested whether LDL receptor (LDLR)
      expression was required for cholesterol reduction by treating control and LDLR
      knockout mice with two forms of thyroid hormone T(3) and 3,5-diiodo-l-thyronine.
      High doses of both 3,5-diiodo-l-thyronine and T(3) dramatically reduced
      circulating total and very low-density lipoprotein/LDL cholesterol (~70%) and
      were associated with reduced plasma T(4) level. The cholesterol reduction was
      especially evident in the LDLR-knockout mice. Circulating levels of both
      apolipoprotein B (apo)B48 and apoB100 were decreased. Surprisingly, this
      reduction was not associated with increased protein or mRNA expression of the
      hepatic lipoprotein receptors LDLR-related protein 1 or scavenger receptor-B1.
      Liver production of apoB was markedly reduced, whereas triglyceride production
      was increased. Thus, thyroid hormones reduce apoB lipoproteins via a non-LDLR
      pathway that leads to decreased liver apoB production. This suggests that drugs
      that operate in a similar manner could be a new therapy for patients with genetic
      defects in the LDLR.

PMID- 22948213
TI  - The vitamin D analog ED-71 is a potent regulator of intestinal phosphate
      absorption and NaPi-IIb.
AB  - The vitamin D analog ED-71 [1alpha,25-dihydroxy-2beta-(3-hydroxypropyloxy)vitamin
      D(3)] has been approved for treatment of osteoporosis in Japan, but its effects
      on mineral metabolism have not been fully explored. We investigated the actions
      of ED-71 on phosphate (Pi) absorption and induction of the intestinal
      sodium/phosphate cotransporters. Oral treatment of vitamin D-deficient rats with
      ED-71 (20 pmol every other day for 8 d) produced a maximal 8-fold increase in
      duodenal Pi absorption, measured by the in situ loop method, whereas 1,25
      dihyroxyvitamin D(3) [1,25(OH)(2)D(3]), at doses up to 150 pmol, had no effect.
      This action of ED-71 was attributable to a dramatic 24-fold induction of sodium
      dependent Pi transporter type IIb (NaPi-IIb) mRNA in the duodenum; Pit-1 and Pit
      2 mRNA levels were not increased. In vitamin D-replete rats, ED-71 treatment (50
      pmol) at 72 and 24 h before death increased NaPi-IIb mRNA in the duodenum and
      jejunum, but not the ileum, whereas 1,25(OH)(2)D(3) at 1000 pmol was ineffective
      in all segments. Single oral doses of ED-71 increased mouse intestinal NaPi-IIb
      mRNA and protein between 6 and 24 h. Surprisingly, rat lung NaPi-IIb was not
      increased by ED-71, despite its coexpression with the vitamin D receptor in
      alveolar type II cells. However, ED-71 did not induce intestinal NaPi-IIb in
      vitamin D receptor-ablated mice. The greater potency of ED-71 than
      1,25(OH)(2)D(3) on NaPi-IIb appears to be due to much higher and more prolonged
      levels of ED-71 in the circulation. In summary, ED-71, due to its disparate
      pharmacokinetics, is a much more potent inducer of intestinal Pi absorption and
      NaPi-IIb than 1,25(OH)(2)D(3), suggesting a role for this analog in the treatment
      of Pi-wasting disorders.

PMID- 22948214
TI  - rpS6 Regulates blood-testis barrier dynamics by affecting F-actin organization
      and protein recruitment.
AB  - During spermatogenesis, preleptotene spermatocytes residing near the basement
      membrane of the seminiferous tubule must traverse the blood-testis barrier (BTB)
      at stage VIII-IX of the epithelial cycle to continue their development in the
      adluminal compartment. Unlike other blood-tissue barriers (e.g. the blood-brain
      barrier) that are created by the endothelial tight junction (TJ) barrier of
      capillaries, the BTB is created by specialized junctions between Sertoli cells in
      which TJ coexists with basal ectoplasmic specialization (basal ES, a testis
      specific adherens junction). The basal ES is typified by the presence of tightly
      packed actin filament bundles sandwiched between cisternae of endoplasmic
      reticulum and the apposing plasma membranes of Sertoli cells. These actin
      filament bundles also confer unusual adhesive strength to the BTB. Yet the
      mechanisms by which these filamentous actin (F-actin) networks are regulated from
      the bundled to the debundled state to facilitate the transit of spermatocytes
      remain elusive. Herein, we provide evidence that ribosomal protein S6 (rpS6), the
      downstream signaling molecule of the mammalian target of rapamycin complex 1
      (mTORC1) pathway, is a major regulator of F-actin organization and adhesion
      protein recruitment at the BTB. rpS6 is restrictively and spatiotemporally
      activated at the BTB during the epithelial cycle. An activation of rpS6 led to a
      disruption of the Sertoli cell TJ barrier and BTB integrity. Its silencing in
      vitro or in vivo by using small interfering RNA duplexes or short hairpin RNA was
      found to promote the Sertoli cell TJ permeability barrier by the recruitment of
      adhesion proteins (e.g. claudin-11 and occludin) to the BTB. Thus, rpS6 in the
      mTORC1 pathway regulates BTB restructuring via its effects on the F-actin
      organization and protein recruitment at the BTB.

PMID- 22948215
TI  - Creation and preliminary characterization of a leptin knockout rat.
AB  - Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various
      pathways centered on food intake and energy expenditure, including insulin
      sensitivity, fertility, immune system, and bone metabolism. Here, using zinc
      finger nuclease technology, we created the first leptin knockout rat. Homozygous
      leptin null rats are obese with significantly higher serum cholesterol,
      triglyceride, and insulin levels than wild-type controls. Neither gender produced
      offspring despite of repeated attempts. The leptin knockout rats also have
      depressed immune system. In addition, examination by microcomputed tomography of
      the femurs of the leptin null rats shows a significant increase in both
      trabecular bone mineral density and bone volume of the femur compared with wild
      type littermates. Our model should be useful for many different fields of
      studies, such as obesity, diabetes, and bone metabolism-related illnesses.

PMID- 22948216
TI  - Phosphodiesterase type 5 inhibition reverts prostate fibroblast-to-myofibroblast
      trans-differentiation.
AB  - Phosphodiesterase type 5 (PDE5) inhibitors have been demonstrated to improve
      lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH).
      Because BPH is primarily driven by fibroblast-to-myofibroblast trans
      differentiation, this study aimed to evaluate the potential of the PDE5 inhibitor
      vardenafil to inhibit and reverse trans-differentiation of primary human
      prostatic stromal cells (PrSC). Vardenafil, sodium nitroprusside, lentiviral
      delivered short hairpin RNA-mediated PDE5 knockdown, sodium orthovanadate, and
      inhibitors of MAPK kinase, protein kinase G, Ras homolog family member (Rho) A,
      RhoA/Rho kinase, phosphatidylinositol 3 kinase and protein kinase B (AKT) were
      applied to PrSC treated with basic fibroblast growth factor (fibroblasts) or
      TGFbeta1 (myofibroblasts) in vitro, in chicken chorioallantoic membrane
      xenografts in vivo, and to prostatic organoids ex vivo. Fibroblast-to
      myofibroblast trans-differentiation was monitored by smooth muscle cell actin and
      IGF binding protein 3 mRNA and protein levels. Vardenafil significantly
      attenuated TGFbeta1-induced PrSC trans-differentiation in vitro and in
      chorioallantoic membrane xenografts. Enhancement of nitric oxide/cyclic guanosine
      monophosphate signaling by vardenafil, sodium nitroprusside, or PDE5 knockdown
      reduced smooth muscle cell actin and IGF binding protein 3 mRNA and protein
      levels and restored fibroblast-like morphology in trans-differentiated
      myofibroblast. This reversal of trans-differentiation was not affected by MAPK
      kinase, protein kinase G, RhoA, or RhoA/Rho kinase inhibition, but vardenafil
      attenuated phospho-AKT levels in myofibroblasts. Consistently,
      phosphatidylinositol 3 kinase or AKT inhibition induced reversal of trans
      differentiation, whereas the tyrosine phosphatase inhibitor sodium orthovanadate
      abrogated the effect of vardenafil. Treatment of prostatic organoids with
      vardenafil ex vivo reduced expression of myofibroblast markers, indicating
      reverse remodeling of stroma towards a desired higher fibroblast/myofibroblast
      ratio. Thus, enhancement of the nitric oxide/cyclic guanosine monophosphate
      signaling pathway by vardenafil attenuates and reverts fibroblast-to
      myofibroblast trans-differentiation, hypothesizing that BPH patients might
      benefit from long-term therapy with PDE5 inhibitors.

PMID- 22948217
TI  - cAMP-mediated and metabolic amplification of insulin secretion are distinct
      pathways sharing independence of beta-cell microfilaments.
AB  - Insulin secretion is triggered by an increase in the cytosolic calcium
      concentration ([Ca(2+)](c)) in beta-cells. Ca(2+)-induced exocytosis of insulin
      granules can be augmented by metabolic amplification (unknown signals generated
      through glucose metabolism) or neurohormonal amplification (in particular cAMP
      mediated). Functional actin microfilaments are not required for metabolic
      amplification, but their possible role in cAMP-mediated amplification is unknown.
      It is also uncertain whether cAMP (generated in response to glucose) is
      implicated in metabolic amplification. These questions were addressed using
      isolated mouse islets. cAMP levels were increased by phosphodiesterase inhibition
      (with isobutylmethylxanthine) and adenylate-cyclase stimulation (with forskolin
      or glucagon-like peptide-1, 7-36 amide). Raising cAMP levels had no steady-state
      impact on actin polymerization in control islets. Neither disruption
      (depolymerization by latrunculin) nor stabilization (polymerization by
      jasplakinolide) of actin microfilaments was counteracted by cAMP. Both changes
      increased both phases of glucose- or tolbutamide-induced insulin secretion but
      did not prevent further amplification by cAMP. These large changes in secretion
      were not caused by changes in [Ca(2+)](c), which was only slightly increased by
      cAMP. Both phases of insulin secretion were larger in response to glucose than
      tolbutamide, although [Ca(2+)](c) was lower. This difference in secretion, which
      reflects metabolic amplification, was independent of microfilaments, was not
      attributable to differences in cAMP, and persisted in presence of dibutyryl-cAMP
      or when cAMP levels were variably raised by isobutylmethylxanthine + forskolin or
      glucagon-like peptide-1, 7-36 amide. We conclude that metabolic and cAMP-mediated
      amplification of insulin secretion are distinct pathways that accelerate
      acquisition of release competence by insulin granules that can access exocytotic
      sites without intervention of microfilaments.

PMID- 22948218
TI  - Chemerin, a novel regulator of follicular steroidogenesis and its potential
      involvement in polycystic ovarian syndrome.
AB  - Polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome associated with
      follicle growth arrest, minimal granulosa cell proliferation, dysregulated sex
      hormone profile, hyperthecosis, and insulin resistance. Using a 5alpha
      dihydrotestosterone (DHT)-induced rat model that recapitulates the reproductive
      and metabolic phenotypes of human PCOS, we have examined the steroidogenic
      capability of granulosa cells from DHT-treated rats. Gene expression of several
      key steroidogenic enzymes including p450 side-chain cleavage enzyme (p450scc),
      aromatase, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenase
      17beta, and hydroxysteroid dehydrogenase-3beta were markedly lower in DHT-treated
      rats than the controls, although the responsiveness of their granulosa cells to
      FSH was higher. Expression of the adipokine chemerin and its receptor, chemokine
      receptor-like 1, was evident in control and DHT-treated rats, with significantly
      higher ovarian mRNA abundances and protein contents of chemerin and its receptor.
      Recombinant chemerin decreases basal estradiol secretion in granulosa cells from
      DHT-treated rats. When the inhibitory role of chemerin on steroidogenesis was
      further examined in vitro, chemerin suppressed FSH-induced progesterone and
      estradiol secretion in cultured preantral follicles and granulosa cells. Chemerin
      also inhibits FSH-induced aromatase and p450scc expression in granulosa cells.
      Overexpression of nuclear receptors NR5a1 and NR5a2 promotes p450scc and
      aromatase expression, respectively, which is suppressed by chemerin. These
      findings suggest that chemerin is a novel negative regulator of FSH-induced
      follicular steroidogenesis and may contribute to the pathogenesis of PCOS.

PMID- 22948219
TI  - Testosterone and 17beta-estradiol induce glandular prostatic growth, bladder
      outlet obstruction, and voiding dysfunction in male mice.
AB  - Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are
      common in older men and can contribute to lower urinary tract symptoms that
      significantly impact quality of life. Few existing models of BOO and BPH use
      physiological levels of hormones associated with disease progression in humans in
      a genetically manipulable organism. We present a model of BPH and BOO induced in
      mice with testosterone (T) and 17beta-estradiol (E(2)). Male mice were surgically
      implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E(2)
      (T+E(2)). After 2 and 4 months of hormone treatment, we evaluated voiding
      patterns and examined the gross morphology and histology of the bladder, urethra,
      and prostate. Mice treated with T+E(2) developed significantly larger bladders
      than untreated mice, consistent with BOO. Some mice treated with T+E(2) had
      complications in the form of bladder hypertrophy, diverticula, calculi, and
      eventual decompensation with hydronephrosis. Hormone treatment caused a
      significant decrease in the size of the urethral lumen, increased prostate mass,
      and increased number of prostatic ducts associated with the prostatic urethra,
      compared with untreated mice. Voiding dysfunction was observed in mice treated
      with T+E(2), who exhibited droplet voiding pattern with significantly decreased
      void mass, shorter void duration, and fewer sustained voids. The constellation of
      lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding
      dysfunction seen in male mice treated with T+E(2) is consistent with BPH in men.
      This model is suitable for better understanding molecular mechanisms and for
      developing novel strategies to address BPH and BOO.

PMID- 22948220
TI  - Biosynthesis of 3-iodothyronamine (T1AM) is dependent on the sodium-iodide
      symporter and thyroperoxidase but does not involve extrathyroidal metabolism of
      T4.
AB  - 3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with
      unknown biosynthetic origins. Structural similarities have led to the hypothesis
      that T(1)AM is an extrathyroidal metabolite of T(4). This study uses an isotope
      labeled T(4) [heavy-T(4) (H-T(4))] that can be distinguished from endogenous T(4)
      by mass spectrometry, which allows metabolites to be identified based on the
      presence of this unique isotope signature. Endogenous T(1)AM levels depend upon
      thyroid status and decrease upon induction of hypothyroidism. However, in
      hypothyroid mice replaced with H-T(4), the isotope-labeled H-T(3) metabolite is
      detected, but no isotope-labeled T(1)AM is detected. These data suggest that
      T(1)AM is not an extrathyroidal metabolite of T(4), yet is produced by a process
      that requires the same biosynthetic factors necessary for T(4) synthesis.

PMID- 22948221
TI  - Isoorientin reverts TNF-alpha-induced insulin resistance in adipocytes activating
      the insulin signaling pathway.
AB  - Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic
      effects but unexplored mechanisms of action. To gain insight into its
      antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7
      nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by
      murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO
      stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with
      insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and
      human (60%) adipocytes made resistant to insulin by treatment with TNF-alpha,
      compared with the incorporation induced in these cells by rosiglitazone. ISO
      induction of glucose uptake in adipocytes was abolished by inhibitors of the
      insulin signaling pathway. These inhibitors also blocked the proper
      phosphorylation of insulin signaling pathway components induced by ISO in both
      insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated
      the transcription of genes encoding components of insulin signaling pathway in
      murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show
      here that ISO exerts its antidiabetic effects by activating the insulin signaling
      pathway in adipocytes, reverts the insulin resistance caused in these cells by
      TNF-alpha by stimulating the proper phosphorylation of proteins in this signaling
      pathway, and induces the expression of genes encoding these proteins.

PMID- 22948222
TI  - Double-stranded RNA-activated protein kinase is a key modulator of insulin
      sensitivity in physiological conditions and in obesity in mice.
AB  - The molecular integration of nutrient- and pathogen-sensing pathways has become
      of great interest in understanding the mechanisms of insulin resistance in
      obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate
      molecule that may provide cross talk between inflammatory and metabolic
      signaling. The present study was performed to determine, first, the role of PKR
      in modulating insulin action and glucose metabolism in physiological situations,
      and second, the role of PKR in insulin resistance in obese mice. We used Pkr(-/-)
      and Pkr(+/+) mice to investigate the role of PKR in modulating insulin
      sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and
      adipose tissue in response to a high-fat diet. Our data show that in lean Pkr(-/
      ) mice, there is an improvement in insulin sensitivity, and in glucose tolerance,
      and a reduction in fasting blood glucose, probably related to a decrease in
      protein phosphatase 2A activity and a parallel increase in insulin-induced
      thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of
      obese mice and can induce insulin resistance by directly binding to and inducing
      insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly
      through modulation of c-Jun N-terminal kinase and inhibitor of kappaB kinase
      beta. Pkr(-/-) mice were protected from high-fat diet-induced insulin resistance
      and glucose intolerance and showed improved insulin signaling associated with a
      reduction in c-Jun N-terminal kinase and inhibitor of kappaB kinase beta
      phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin
      sensitivity under normal physiological conditions, probably by modulating protein
      phosphatase 2A activity and serine-threonine kinase phosphorylation, and
      certainly, this kinase may represent a central mechanism for the integration of
      pathogen response and innate immunity with insulin action and metabolic pathways
      that are critical in obesity.

PMID- 22948223
TI  - Effect of weight reduction on the quality of life in obese patients with
      fibromyalgia syndrome: a randomized controlled trial.
AB  - The aim of the study was to examine whether weight reduction can result in
      improvement of fibromyalgia impact questionnaire (FIQ) in the patients with
      fibromyalgia syndrome (FMS). This study was a randomized controlled trial. Obese
      patients with fibromyalgia were randomly assigned to 6-month dietary weight loss
      (n = 41) and no weight loss (n = 42) groups. Patients were assessed at baseline
      and at 6 months. The primary outcome measure was FIQ. Secondary measures included
      the tender point (TP) examination, Beck Depression Inventory-II, and Pittsburg
      Sleep Quality Index. Compared to the control group, patients who underwent weight
      reduction obtained significantly better FIQ (p = 0.007), lower mean TP count (p =
      0.015), and lower mean TP pain rating in the lower body (p < 0.001). Patients who
      lost weight had less depression and better sleep quality than the controls.
      Patients who lost weight had significantly lower interleukin 6 and C-reactive
      protein levels than those in the control group (p = 0.034 and p = 0.007,
      respectively). Weight loss in obese patients with FMS leads to significant
      improvement in the quality of life as shown by the decrease in the FIQ score.
      Depression, sleep quality, and tender point count are also significantly improved
      by weight loss in obese patients with fibromyalgia. Our results suggest that
      weight reduction should be a part of fibromyalgia treatment.

PMID- 22948224
TI  - Intraosseous pneumatocysts: a case based review.
AB  - Intraosseous pneumatocysts are benign gaseous bone lesions, generally
      asymptomatic and incidentally discovered on X-ray. These characteristics explain
      why these lesions are unknown to most practitioners and their low representation
      in medical literature. The description of an incidentally discovered iliac
      pneumatocyst gives us the opportunity to provide a review of available medical
      literature on these frequent, but poorly known lesions.

PMID- 22948225
TI  - Adherence to uric acid treatment guidelines in a rheumatology clinic.
AB  - The aim of this study was to evaluate adherence to recommended serum uric acid
      levels in the rheumatology outpatients department of a university teaching
      hospital. We performed a retrospective study of all patients with a definitive
      diagnosis of gout attending our subspecialty gout clinic between 1 January 2010
      and 31 December 2010. We evaluated adherence with two recently suggested uric
      acid thresholds, <300 MUmol/L (<5 mg/dL) and <360 MUmol/L (<6 mg/dL). Patient
      management was judged to adhere to the guidelines if either (1) the latest serum
      uric acid level was less than the specified guideline targets or (2) uric acid
      lowering therapy was titrated upwards or the agent changed if the serum uric acid
      was above the guideline targets. One hundred two patients with a definitive
      diagnosis of gout attended the outpatients department between 1 January 2010 and
      31 December 2010 and were included in the study. Median serum uric acid level was
      331 MUmol/L (IQR 276-456 MUmol/L). Eighty-six patients (84 %) were treated with
      allopurinol, six patients (6 %) were treated with febuxostat (one of whom also
      received probenecid), and one with rasburicase. In 80 patients (78 %), the
      management adhered to a target guideline of <360 MUmol/L (<6 mg/dL). In 66
      patients (65 %), the management adhered to a target guideline of <300 MUmol/L (<5
      mg/dL). A treat-to-target approach has the potential to improve patient outcomes
      in the management of gouty arthritis. Our study shows encouraging results with
      the majority of patients on appropriate therapy and reaching recommended targets.

PMID- 22948228
TI  - A novel di-compartmental bis-(2-hydroxyisophtalamide) macrocyclic ligand and its
      mononuclear Cu(II) and Ni(II) complexes.
AB  - The synthesis and characterisation of the new di-compartmental bis-(2
      hydroxyisophtalamide) macrocyclic pro-ligand, LH(6), which comprises two phenol
      diamide units linked by ethylene bridges, is herein reported, together with its
      corresponding di-phenolate salt, [NBu(4)](2)[LH(4)]. The three macrocyclic
      compounds, [LH(4)(OMe)(2)] (protected ligand), LH(6) and [LH(4)][NBu(4)](2) were
      fully characterised including X-ray crystallography for [LH(4)(OMe)(2)] and
      [NBu(4)](2)[LH(4)]. The results of solid-state and solution studies have
      indicated that the macrocycle can adopt specific conformations, which are
      influenced by H-bonding interactions as well as the deviation of the amide
      carbonyl relative to the phenol plane. LH(6) reacts with
      M(II)(acetate)(2).(H(2)O)(6) (M = Ni, Cu) in a 1 : 1 ratio in the presence of 4
      eq of [NBu(4)](OH) in methanol to afford the dianionic [M(LH(2))](2-) complexes,
      (2-) and (2-), respectively. The X-ray crystallography, EPR, NMR and UV-vis
      spectroscopic data, combined with DFT calculations, indicate that (2-) and (2-)
      are unique unsymmetrical square planar mononuclear complexes that are
      intramolecularly H-bonded. Thus, one macrocyclic compartment contains a M(II)
      N(2)O(2) centre resulting from the tetra-anionic di-phenolato di-amidato
      ligation; the other compartment possesses two protonated amide N-H groups that
      are H-bonded the coordinated phenolate O atoms. This represents a unique example
      in which a phenolate is both coordinated and intramolecularly H-bonded. This H
      bonding appears unusually strong as revealed by N(H/D) exchange experiments; and
      may be responsible for the stability of the mononuclear complex, and the
      difficulty in isolating the corresponding dinuclear complex [M(2)(L)](2-).

PMID- 22948226
TI  - Histone phosphorylation: a chromatin modification involved in diverse nuclear
      events.
AB  - Histone posttranslational modifications are key components of diverse processes
      that modulate chromatin structure. These marks function as signals during various
      chromatin-based events, and act as platforms for recruitment, assembly or
      retention of chromatin-associated factors. The best-known function of histone
      phosphorylation takes place during cellular response to DNA damage, when
      phosphorylated histone H2A(X) demarcates large chromatin domains around the site
      of DNA breakage. However, multiple studies have also shown that histone
      phosphorylation plays crucial roles in chromatin remodeling linked to other
      nuclear processes. In this review, we summarize the current knowledge of histone
      phosphorylation and describe the many kinases and phosphatases that regulate it.
      We discuss the key roles played by this histone mark in DNA repair, transcription
      and chromatin compaction during cell division and apoptosis. Additionally, we
      describe the intricate crosstalk that occurs between phosphorylation and other
      histone modifications and allows for sophisticated control over the chromatin
      remodeling processes.

PMID- 22948227
TI  - MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins.
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionarily
      conserved catabolic process necessary for normal recycling of cellular
      constituents and for appropriate response to cellular stress. Although several
      genes belonging to the core molecular machinery involved in autophagosome
      formation have been discovered, relatively little is known about the nature of
      signaling networks controlling autophagy upon intracellular or extracellular
      stimuli. We discovered ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) as
      novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation and
      transformation. Based on the role of these proteins in the autophagic process, we
      demonstrated that MAPK15 is indeed localized to autophagic compartments and
      increased, in a kinase-dependent fashion, ATG8-like proteins lipidation,
      autophagosome formation and SQSTM1 degradation, while decreasing LC3B inhibitory
      phosphorylation. Interestingly, we also identified a conserved LC3-interacting
      region (LIR) in MAPK15 responsible for its interaction with ATG8-like proteins,
      for its localization to autophagic structures and, consequently, for stimulation
      of the formation of these compartments. Furthermore, we reveal that MAPK15
      activity was induced in response to serum and amino-acid starvation and that this
      stimulus, in turn, required endogenous MAPK15 expression to induce the autophagic
      process. Altogether, these results suggested a new function for MAPK15 as a
      regulator of autophagy, acting through interaction with ATG8 family proteins.
      Also, based on the key role of this process in several human diseases, these
      results supported the use of this MAP kinase as a potential novel therapeutic
      target.

PMID- 22948229
TI  - Radiotherapy for craniopharyngioma.
AB  - Radiotherapy remains the mainstay of multidisciplinary management of patients
      with incompletely resected and recurrent craniopharyngioma. Advances in imaging
      and radiotherapy technology offer new alternatives with the principal aim of
      improving the accuracy of treatment and reducing the volume of normal brain
      receiving significant radiation doses. We review the available technologies,
      their technical advantages and disadvantages and the published clinical results.
      Fractionated high precision conformal radiotherapy with image guidance remains
      the gold standard; the results of single fraction treatment are disappointing and
      hypofractionation should be used with caution as long term results are not
      available. There is insufficient data on the use of protons to assess the
      comparative efficacy and toxicity. The precision of treatment delivery needs to
      be coupled with experienced infrastructure and more intensive quality assurance
      to ensure best treatment outcome and this should be carried out within
      multidisciplinary teams experienced in the management of craniopharyngioma. The
      advantages of the combined skills and expertise of the team members may outweigh
      the largely undefined clinical gain from novel radiotherapy technologies.

PMID- 22948230
TI  - Obesity, anthropometric measures and chronic kidney disease complications.
AB  - BACKGROUND/AIMS: Anthropometric measures such as body mass index (BMI) and waist
      circumference (WC) have differential associations with incident chronic kidney
      disease (CKD) and mortality. We examined the associations of BMI and WC with
      various CKD complications. METHODS: We conducted a cross-sectional analysis of
      2,853 adult participants with CKD in the National Health and Nutrition
      Examination Surveys 1999-2006. The associations of BMI and WC (both as
      categorical and continuous variables) with CKD complications such as anemia,
      secondary hyperparathyroidism, hyperphosphatemia, metabolic acidosis,
      hypoalbuminemia and hypertension were examined using logistic regression models
      while adjusting for relevant confounding variables. RESULTS: When examined as a
      continuous variable, an increase in BMI by 2 points and in WC by 5 cm was
      associated with higher odds of secondary hyperparathyroidism, hypoalbuminemia and
      hypertension among those with CKD. CKD participants with BMI >=30 have higher
      odds of hypoalbuminemia and hypertension than those with BMI <30. CKD
      participants with high WC (>102 cm in men and >88 cm in women) have higher odds
      of hypoalbuminemia and hypertension and lower odds of having anemia than those
      with low WC. CKD participants with BMI <30 and high WC (vs. BMI <30 and low WC)
      were not associated with any increase in CKD complications. CONCLUSIONS:
      Anthropometric measures such as BMI and WC are associated with secondary
      hyperparathyroidism, hypoalbuminemia and hypertension among adults with CKD.
      Higher WC among those with BMI <30 is not associated with CKD complications.

PMID- 22948231
TI  - Characterization of structural changes in aptamer films for controlled release
      nanodevices.
AB  - The dimension of the conformational changes of DNA-aptamers which can be used as
      stimulus-responsive gate-keepers in controlled delivery nanodevices has been
      determined by acoustic wave-based sensors upon molecular recognition of a small
      sized target, adenosine-5'-monophosphate (AMP).

PMID- 22948232
TI  - Evidence that the methylation state of the monoamine oxidase A (MAOA) gene
      predicts brain activity of MAO A enzyme in healthy men.
AB  - Human brain function is mediated by biochemical processes, many of which can be
      visualized and quantified by positron emission tomography (PET). PET brain
      imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters
      revealed that MAO A levels vary widely between healthy men and this variability
      was not explained by the common MAOA genotype (VNTR genotype), suggesting that
      environmental factors, through epigenetic modifications, may mediate it. Here, we
      analyzed MAOA methylation in white blood cells (by bisulphite conversion of
      genomic DNA and subsequent sequencing of cloned DNA products) and measured brain
      MAO A levels (using PET and [(11)C]clorgyline, a radiotracer with specificity for
      MAO A) in 34 healthy non-smoking male volunteers. We found significant
      interindividual differences in methylation status and methylation patterns of the
      core MAOA promoter. The VNTR genotype did not influence the methylation status of
      the gene or brain MAO A activity. In contrast, we found a robust association of
      the regional and CpG site-specific methylation of the core MAOA promoter with
      brain MAO A levels. These results suggest that the methylation status of the MAOA
      promoter (detected in white blood cells) can reliably predict the brain
      endophenotype. Therefore, the status of MAOA methylation observed in healthy
      males merits consideration as a variable contributing to interindividual
      differences in behavior.

PMID- 22948233
TI  - FTO, RNA epigenetics and epilepsy.
AB  - Several recent landmark papers describing N(6) -methyladenosine (m(6) A) RNA
      modifications have provided valuable new insights as to the importance of m(6) A
      in the RNA transcriptome and in furthering the understanding of RNA epigenetics.
      One endogenous enzyme responsible for demethylating RNA m(6) A, FTO, is highly
      expressed in the CNS and is likely involved in mRNA metabolism, splicing or other
      nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding
      transcripts that bind to target mRNAs and inhibit subsequent translation, are
      highly expressed in the CNS and are associated with several neurological
      disorders, including epilepsy. miRNAs frequently bind to recognition sequences in
      the 3'UTR, a region that is also enriched for m(6) A. Certain specific miRNAs are
      upregulated by neuronal activity and are coupled to epileptogenesis; these miRNAs
      contain a consensus m(6) A site that if methylated could possibly regulate miRNA
      processing or function. This commentary highlights aspects from recent papers to
      propose a functional association between FTO, RNA epigenetics and epilepsy.

PMID- 22948234
TI  - Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell
      growth and migration through downregulation of the PI3K/AKT pathway.
AB  - Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of
      signaling molecules and have previously been shown to be associated with the
      biological behavior of osteosarcoma. However, to date the effects and molecular
      mechanisms of BMP-9 on osteosarcoma progression are unknown. We performed real
      time PCR and western blot analysis to characterize the endogenous expression of
      BMP-9 in osteosarcoma cell lines. We used a recombinant adenovirus expressing BMP
      9 (adBMP-9) to infect osteosarcoma cell lines with relatively low endogenous BMP
      9 expression to determine the functional relevance of BMP-9 overexpression to
      osteosarcoma cell growth and migration in vitro and in vivo, and further
      investigated the expression levels of Ki-67, matrix metallopeptidase-9 (MMP-9),
      phosphoinositide 3-kinase p85alpha (PI3Kp85alpha) and phosphorylated AKT (p-AKT).
      As a result, osteosarcoma cell proliferation and migration were significantly
      diminished by adBMP-9, indicated by MTT and wound-healing assays, and cell
      apoptosis was markedly induced, indicated by Hoechst 33342/PI assay and Annexin V
      FITC apoptosis detection. When BMP-9 expression was enhanced, the expression of
      PI3Kp85alpha, p-AKT, Ki-67 and MMP-9 was downregulated in osteosarcoma cells. In
      addition, the tumor volumes in MG-63 and HOS subcutaneous nude mouse models
      treated with adBMP-9 were significantly smaller compared to those of the ad-GFP
      group. These results suggested that the enhanced expression of BMP-9 in
      osteosarcoma cells by adBMP-9 exerted inhibitory effects on growth and migration
      of osteosarcoma cells possibly via blockade of the PI3K/AKT signaling pathway.

PMID- 22948235
TI  - Attachment styles and outcome of psychoanalytic psychotherapy for children and
      adolescents.
AB  - BACKGROUND: Until now few studies have proven that an attachment style can be
      changed in the course of psychotherapy and that the attachment style has an
      impact on the therapy outcome. In particular, there is a lack of studies about
      these relationships in long-term psychoanalytic psychotherapy with children and
      adolescents. SAMPLING AND METHODS: Seventy-one children with mental disorders
      receiving long-term outpatient psychodynamic psychotherapy were assessed 4 times
      using the Heidelberg Attachment Style Rating for Children and Adolescents. The
      measurements were conducted at the beginning of treatment, at the 25th treatment
      session, at the end of treatment and 1 year after the completion of treatment.
      RESULTS: The results showed a significant change in attachment style during
      treatment. The proportion of children and adolescents with a secure attachment
      style increased from 23% to 63%. There was no significant difference in the
      attachment style between patients with good and poor treatment outcome, but a
      significant relationship between secure attachment and the number of treatment
      sessions could be demonstrated. CONCLUSIONS: A reorientation towards a secure
      main attachment style over the course of psychotherapy is possible. However,
      attachment style seems to be not a moderator but a mediator for the outcome of
      psychoanalytic psychotherapy in children and adolescents.

PMID- 22948236
TI  - Abstracts of CIRSE (Cardiovascular and Interventional Radiological Society of
      Europe) 2012. September 15-19, 2012. Lisbon, Portugal.

PMID- 22948237
TI  - Reduced blood alcohol concentration in suicide victims in response to a new
      national alcohol policy in slovenia.
AB  - BACKGROUND: Addiction is a major social and health problem. Studies on suicide
      and alcohol at the individual and aggregated level have confirmed a link between
      alcohol and suicide. AIM: To assess the impact of the new national alcohol policy
      in Slovenia on the blood alcohol concentration (BAC) in BAC-positive suicide
      victims before, during and after the implementation of the new national alcohol
      policy in 2003. METHOD: Blood samples were collected by forensic pathologists
      during medicolegal autopsies of suicide victims in order to establish their BAC
      levels at the time of death. BAC was measured using two routine independent
      headspace gas chromatography methods (HSS-GC-FID) and expressed in grams per
      kilogram. RESULTS: During the period before the implementation of the act which
      limited the availability of alcohol in Slovenia, the BACs of BAC-positive suicide
      victims were higher than those tested in the period after the implementation of
      the act. CONCLUSION: Despite certain limitations, this study demonstrates that
      legislation measures restricting alcohol availability may be an effective measure
      of BAC reduction in BAC-positive suicide victims.

PMID- 22948238
TI  - Healthy lifestyle: need for action.

PMID- 22948239
TI  - Relationship between serum magnesium levels and cardiovascular events in chronic
      kidney disease patients.
AB  - BACKGROUND: Magnesium is an essential ion for all living cells because over 300
      enzymes require the presence of magnesium for their catalytic action. To date, no
      group has evaluated magnesium as a cardiovascular risk factor in chronic kidney
      disease (CKD) subjects, in which closely interrelated factors and potential
      confounders such as endothelial dysfunction, insulin resistance (the homeostasis
      model assessment (HOMA) index) and inflammation (expressed as serum C-reactive
      protein (CRP) levels) were also considered. METHODS: Between March 2006 and
      December 2010, 283 CKD patients were followed up for time-to-event analysis until
      the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent
      vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent
      vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were
      assessed noninvasively using high-resolution ultrasound. RESULTS: From the
      univariate analysis of FMD, it appears that a higher magnesium level is
      associated with less endothelial dysfunction. When a multivariate analysis was
      performed, magnesium and estimated glomerular filtration rates (eGFR) maintained
      a strong positive correlation with FMD, supporting the hypothesis that higher
      levels of magnesium may protect against endothelial damage. In univariate Cox
      proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA
      index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood
      pressure, serum phosphate and intact parathormone emerged as significant
      predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly
      higher cardiovascular mortality rates in CKD patients whose serum magnesium
      levels were below 2.05 mg/dl. CONCLUSIONS: This observational cohort study showed
      that magnesium may be an independent predictor of future cardiovascular outcomes
      and is the first study demonstrating such a role in etiologically diagnosed CKD
      patients, across different stages.

PMID- 22948240
TI  - Myocardial deformation by speckle tracking in severe dilated cardiomyopathy.
AB  - BACKGROUND: The high and increasing prevalence of Dilated Cardiomyopathy (DCM)
      represents a serious public health problem. New technologies are being used
      aiming at more accurate diagnoses in order to improve therapeutic approach. In
      this scenario, speckle tracking echocardiography (STE) uses natural myocardial
      markers to analyze the systolic deformation of the left ventricle (LV).
      OBJECTIVE: To measure the longitudinal transmural global strain (GS) of the LV
      through STE in patients with severe DCM, comparing the results with normal
      individuals and with echocardiographic parameters established for the analysis of
      LV systolic function, validating the method in this population. METHODS: We
      studied 71 patients with severe DCM (53 +/- 12 years, 72% men) and 20 controls
      (30 +/- 8 years, 45% men). We obtained LV volumes and ejection fraction by two
      and three-dimensional echocardiography, Doppler parameters, tissue Doppler and GS
      was obtained by STE. RESULTS: Compared to controls, LV volumes were higher in the
      DCM group; however, LVEF and peak velocity of E wave were lower in the latter.
      The myocardial performance index was higher among patients. Myocardial velocities
      at the tissue Doppler (S', e', a') were significantly lower and E/e' ratio was
      higher in the DCM group. The GS was decreased in the DCM group (-5.5% +/- 2.3%)
      when compared to controls (-14.0% +/- 1.8%). CONCLUSION: In this study, GS was
      significantly lower in patients with severe DCM, bringing new perspectives for
      therapeutic approaches in this specific population.

PMID- 22948241
TI  - Assessment of cardiac allograft vasculopathy in cardiac transplantation:
      experience of a Brazilian center.
AB  - BACKGROUND: Cardiac transplantation continues to be the treatment of choice for
      heart failure refractory to optimized treatment. Two methods have high
      sensitivity for diagnosing allograft rejection episodes and cardiac allograft
      vasculopathy (CAV), important causes of mortality after transplantation.
      OBJECTIVE: To assess the relationship between intravascular ultrasound (IVUS)
      results and endomyocardial biopsy (BX) reports in the follow-up of patients
      undergoing cardiac transplantation in a Brazilian reference service. METHODS: A
      retrospective epidemiological observational study was carried out with patients
      undergoing orthotopic cardiac transplantation from 2000 to 2009. The study
      assessed the medical records of those patients and the results of the IVUS and BX
      routinely performed in the clinical post-transplant follow-up, as well as the
      therapy used. RESULTS: Of the 77 patients assessed, 63.63% were males, their ages
      ranging from 22 to 69 years. Regarding the IVUS results, 33.96% of the patients
      were classified as Stanford class I, and 32.08%, as Stanford class IV. Of the 143
      BX reports, 51.08% were 1R, and 0.69%, 3R. The Quilty effect was described in
      14.48% of the BX reports. All patients used antiproliferative agents, 80.51% used
      calcineurin inhibitors, and 19.48% used proliferation signal inhibitors.
      CONCLUSION: The assessment of cardiac transplant patients by use of IVUS provides
      detailed information for the early and sensitive diagnosis of CAV, which is
      complemented by histological data derived from BX, establishing a possible causal
      relationship between CAV and humoral rejection episodes.

PMID- 22948242
TI  - Identification of cardiovascular risk factors in parents/caregivers of children
      with heart diseases.
AB  - BACKGROUND: Cardiovascular diseases are one of the major causes of morbidity and
      mortality worldwide. In Brazil, they are the major cause of death. OBJECTIVE: To
      identify cardiovascular risk factors in parents/caregivers of children with heart
      diseases by assessing their nutritional status, health conditions, and life
      style. METHODS: Cross-sectional study of 150 parents or caregivers of children
      with heart diseases who attended a cardiology outpatient clinic. Data on
      identification, lifestyle and health conditions were collected by means of a
      structured questionnaire. For the assessment of the eating habits, a
      questionnaire on eating frequency was used; for the assessment of the nutritional
      status, weight, height, and waist circumference were measured, and the body mass
      index (BMI) was calculated and classified. RESULTS: A total of 155 parents of
      children with heart diseases, predominantly of the female gender (91.6%), were
      evaluated; their mean age was 35.0 +/- 10.6 years. The most prevalent risk
      factors were sedentary lifestyle (85.2%), obesity (28%) and hypertension (22.6%).
      As regards the eating habits, a high frequency of intake of red meat, margarine,
      vegetable oil, and sugar and low intake of fish were observed. Comparison between
      genders showed a significant difference in relation to obesity, as detected by
      BMI, and hypertension, both more frequent among women. Waist circumference
      measurement also showed a higher cardiovascular risk in women. CONCLUSION:
      Cardiovascular risk factors such as excess weight, sedentary lifestyle, and
      hypertension as well as inadequate eating habits such as a high frequency of
      intake of saturated fat and cholesterol and low intake of unsaturated fat were
      identified in the parents/caregivers assessed.

PMID- 22948244
TI  - Three dimensional mapping of strontium in bone by dual energy K-edge subtraction
      imaging.
AB  - The bones of many terrestrial vertebrates, including humans, are continually
      altered through an internal process of turnover known as remodeling. This process
      plays a central role in bone adaptation and disease. The uptake of fluorescent
      tetracyclines within bone mineral is widely exploited as a means of tracking new
      tissue formation. While investigation of bone microarchitecture has undergone a
      dimensional shift from 2D to 3D in recent years, we lack a 3D equivalent to
      fluorescent labeling. In the current study we demonstrate the ability of
      synchrotron radiation dual energy K-edge subtraction (KES) imaging to map the 3D
      distribution of elemental strontium within rat vertebral samples. This approach
      has great potential for ex vivo analysis of preclinical models and human tissue
      samples. KES also represents a powerful tool for investigating the pharmokinetics
      of strontium-based drugs recently approved in many countries around the globe for
      the treatment of osteoporosis.

PMID- 22948243
TI  - A small molecule that targets r(CGG)(exp) and improves defects in fragile X
      associated tremor ataxia syndrome.
AB  - The development of small molecule chemical probes or therapeutics that target RNA
      remains a significant challenge despite the great interest in such compounds. The
      most significant barrier to compound development is defining which chemical and
      RNA motif spaces interact specifically. Herein, we describe a bioactive small
      molecule probe that targets expanded r(CGG) repeats, or r(CGG)(exp), that causes
      Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified
      by using information on the chemotypes and RNA motifs that interact.
      Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3
      b]carbazol-2-ium binds the 5'CGG/3'GGC motifs in r(CGG)(exp) and disrupts a toxic
      r(CGG)(exp)-protein complex in vitro. Structure-activity relationship studies
      determined that the alkylated pyridyl and phenolic side chains are important
      chemotypes that drive molecular recognition of r(CGG)(exp). Importantly, the
      compound is efficacious in FXTAS model cellular systems as evidenced by its
      ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the
      size and number of r(CGG)(exp)-containing nuclear foci. This approach may
      establish a general strategy to identify lead ligands that target RNA while also
      providing a chemical probe to dissect the varied mechanisms by which r(CGG)(exp)
      promotes toxicity.

PMID- 22948245
TI  - Celebrating medical librarians.

PMID- 22948246
TI  - Ischemic stroke: the first 24 hours.
AB  - Patients who have suffered a stroke are often left with a high incidence of
      physical and psychosocial impairments. Institutions must develop and implement
      clinical protocols and pathways to quickly and efficiently initiate evidence
      based stroke therapies.

PMID- 22948247
TI  - Tinnitus evaluation in primary care.
AB  - Tinnitus is a common, yet poorly understood problem. This symptom has many
      causes, both benign as well as serious. Patients can experience significant
      changes in quality-of-life related to symptom severity and duration. This article
      explores causes of tinnitus, evaluation in a primary care setting, and management
      strategies.

PMID- 22948248
TI  - Interleukin-8 content in the stratum corneum as an indicator of the severity of
      inflammation in the lesions of atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease characterized
      by both acute and chronic eczema. Various markers are used to clinically evaluate
      the severity of AD. In order to identify a marker of local severity of AD, we
      measured IL-8, IL-18, vascular endothelial growth factor (VEGF), and transforming
      growth factor-alpha (TGF-alpha) levels in the stratum corneum (scIL-8, scIL-18,
      scVEGF and scTGF-alpha) and evaluated the correlation between the levels of these
      cytokines and the clinical severity scores of localized skin lesions. METHODS:
      Stratum corneum samples were collected from the skin lesions of 50 patients with
      AD using the tape-stripping technique, and the scIL-8, scIL-18, scVEGF and scTGF
      alpha levels were evaluated using the ELISA method. The trans-epidermal water
      loss and skin water content of the lesions were also measured prior to tape
      stripping. RESULTS: The levels of scIL-8, scIL-18, scVEGF and scTGF-alpha were
      significantly higher in patients with AD than in healthy controls. Additionally,
      the levels of scIL-8, scIL-18 and scVEGF significantly correlated with the
      severity of AD. CONCLUSIONS: Among these cytokines, scIL-8 showed the highest
      correlation with the severity scores of lesions in AD as well as other
      parameters. Our results also suggest that measuring cytokines in the stratum
      corneum by using ELISA combined with tape stripping is a convenient method to
      evaluate the severity of skin lesions in AD.

PMID- 22948249
TI  - Design rules for highly transparent electrodes using dielectric constant matching
      of metal oxide with Ag film in optoelectronic devices.
AB  - Using dielectric-constant (epsilon) matching of metal-oxide (MO) with Ag film,
      highly transparent MO/Ag electrodes are demonstrated. At the large-epsilon MO/Ag
      interface, surface-plasmon was suppressed and the film showed increased optical
      transmittance (>70%). OLEDs fabricated using large-epsilon MO/Ag electrodes show
      1.38 times greater luminance than that of devices with small-epsilon MO/Ag.

PMID- 22948250
TI  - Ultra-high-frequency left prefrontal transcranial magnetic stimulation as
      augmentation in severely ill patients with depression: a naturalistic sham
      controlled, double-blind, randomized trial.
AB  - BACKGROUND AND AIM: Repetitive transcranial magnetic stimulation (rTMS) is
      supposed to be not as effective in severe depression as it is in medium
      depression. We evaluated the treatment response to an ultra-high-frequency (UHF;
      30 Hz) approach, which was used to maximize the rTMS efficacy in severely ill
      patients. METHODS: 43 severely depressed patients were included in the
      randomized, double-blind study and received either rTMS with 30 Hz over the left
      dorsolateral prefrontal cortex or sham condition for 3 weeks as an add-on therapy
      to stable antidepressant medication. Hamilton Depression Rating Scale (HDRS) and
      cognitive performance were evaluated before and after the intervention. RESULTS:
      In the active UHF group, the HRDS score was reduced by about 7.2, whereas the
      sham condition showed a smaller reduction of the HDRS score with 3.9. However,
      lithium as a covariant was responsible for the outcome difference, not the group
      of stimulation. No adverse events were reported. Comparing the differences of
      both groups in the pre- and post-study performance in a trail-making test, a
      group effect for the UHF group that was not influenced by the lithium intake was
      observed. CONCLUSION: A 30-Hz left prefrontal rTMS in severely depressed patients
      was safe and no adverse events occurred. Due to a strong effect of lithium as a
      covariate, we could not demonstrate favorable antidepressant effects of the UHF
      stimulation compared to sham. However, we found an improvement of processing
      speed performance in the UHF group, which covaried with improvement of
      psychomotor retardation.

PMID- 22948251
TI  - Self-assembly nanoparticle based tripetaloid structure arrays as surface-enhanced
      Raman scattering substrates.
AB  - This paper reports a novel highly ordered tripetaloid structure array (TPSA)
      which performs very well as an active surface-enhanced Raman scattering (SERS)
      substrate. The TPSA is easily fabricated by anisotropic etching of a self
      assembly silica-nanoparticle bilayer and a subsequent metal deposition step, with
      notable uniformity and reproducibility. Electromagnetic simulation indicates that
      the narrow inter-gaps and edge protrusions in the TPSA act as hot spots. In
      addition, the peak electromagnetic field intensity in the inter-gaps changes
      slightly and periodically as the polarization of the incident light varies from 0
      degrees  to 360 degrees . SERS experiments show that the SERS enhancement factor
      (EF) of a Au-film-covered TPSA is 12 times higher than that of regular Au-film
      over-nanoparticles, and not sensitive to the polarization of the incident light.
      The spatially averaged EF of the TPSA is as high as 5.7 * 10(6), and the local EF
      of its hot spots is much higher.

PMID- 22948252
TI  - Autophagy is decreased in mesenteric fat tissue but not in intestinal mucosae of
      patients with Crohn's disease.
AB  - Crohn's disease (CD) is a chronic intestinal disease with a multifactorial
      etiology. Recently, a role for mesenteric fat has been proposed in CD
      pathophysiology, since fat hypertrophy is detected close to the affected
      intestinal area; however, there are few studies regarding autophagy and the
      hypertrophied mesenteric tissue in CD. To evaluate autophagy-related proteins in
      intestinal mucosae and mesenteric fat of patients with CD and controls, patients
      with ileocecal CD (CD Group) and with non-inflammatory disease (FC Group)
      selected for surgery were studied. Expression of LC3-II was determined by
      immunoblotting of protein extracts. In addition, beclin-1, LC3 and Atg16-L1 RNA
      levels were measured using RT-PCR. The expression of LC3-II was significantly
      lower in the mesenteric tissue and higher in intestinal mucosae of CD when
      compared to controls. However, mRNA expression of autophagy-related proteins was
      similar when comparing the mesenteric fat groups. These findings suggest a defect
      in autophagy activation in the mesenteric fat tissue of CD individuals, which
      could be involved in the maintenance of the inflammatory process.

PMID- 22948253
TI  - [Hyponatremia].
AB  - Hyponatremia is the most common electrolyte disorder in the hospital setting and
      is defined as a serum sodium concentration less than 135 mmol/l. Most patients
      have mild hyponatremia (plasma sodium concentration 130-134 mmol/l) and few if
      any symptoms. Serum sodium concentrations between 120 and 129 mmol/l can be
      associated with lack of concentration, nausea, forgetfulness, apathy and loss of
      balance. Severe hyponatremia (<120 mmol/l) can cause coma or grand mal seizure.
      If hyponatremia occurs acutely (duration <48 h) it will cause more severe
      symptoms than are observed in chronic hyponatremia (>48 h). It is important to
      distinguish between different types of hyponatremia: euvolemic hyponatremia
      causing syndrome of inappropriate antidiuretic hormone secretion(SIADH) also
      known as Schwartz-Bartter syndrome, hypervolemic hyponatremia (cardiac failure
      and liver cirrhosis) and hypovolemic hyponatremia (diarrhoea, vomiting or other
      gastrointestinal fluid losses). Increased levels of ADH and continued fluid
      intake are the pathogenetic causes of all three types of hyponatremia;
      nonetheless, infusion of isotonic fluid is the therapy of choice for hypovolemic
      hyponatremia. In contrast, fluid restriction, lithium carbonate, urea, loop
      diuretics or demeclocycline have been used as therapeutic options to correct
      hyponatremia in euvolemic or hypervolemic hyponatremia but most of these
      therapies have proven to be cumbersome and inefficient. Recently a new class of
      pharmacological agents has become available, the vaptans, orally taken
      vasopressin antagonists. Clinical trials showed them to provide effective,
      specific and safe therapy of hyponatremia. In Europe tolvaptan, the only such
      agent on the market is now approved for the treatment of euvolemic hyponatremia.

PMID- 22948254
TI  - Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone
      morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp. FKI-5513.
AB  - Two new butenolides, designated trichocyalides A and B, were isolated along with
      the known compound harzianolide, from the culture broth of Trichoderma sp. FKI
      5513 by solvent extraction, ODS column chromatography and HPLC. Their structures
      were elucidated by several spectral analyses, showing that they have the common
      skeleton of butenofuranone. Trichocyalides A and B inhibited alkaline phosphatase
      (ALP) activity, a typical marker enzyme of osteoblastic differentiation (IC(50):
      83.0 and 187 MUM, respectively), in bone morphogenetic protein (BMP)-stimulated
      C2C12 myoblasts mutant cells, which stably express BMP receptor activity, whereas
      harzianolide showed no inhibitory activity against ALP even at 500 MUM.

PMID- 22948255
TI  - Genetic mechanisms of variation in erythromycin resistance in Lactobacillus
      rhamnosus strains.

PMID- 22948256
TI  - Oncogenic features of the JMJD2A histone demethylase in breast cancer.
AB  - Estrogen receptor alpha (ERalpha) plays a pivotal role in the genesis of the
      majority of breast tumors. Consequently, endocrine therapy is now routinely
      utilized in the clinic for the treatment of ERalpha-positive breast cancer
      patients. However, how ERalpha activity becomes dysregulated in breast cancer
      cells remains to be elucidated. The aim of this study was to show that the
      histone demethylase JMJD2A, also known as KDM4A, is capable of forming a complex
      with ERalpha in vivo. Moreover, wild-type JMJD2A, but not a catalytically
      impaired mutant, was able to strongly coactivate ERalpha-mediated transcription.
      Consistently, the downregulation of JMJD2A in human T47D breast cancer cells led
      to a decreased expression of cyclin D1, a prominent ERalpha target gene and cell
      cycle regulator. The downregulation of JMJD2A induced a reduction in the growth
      of T47D cells. In addition, we found that JMJD2A is overexpressed in human breast
      tumors both at the mRNA and protein level. Taken together, these data indicate
      that the overexpression of JMJD2A may contribute to breast tumor formation by
      stimulating ERalpha activity and that JMJD2A may be a breast-relevant
      oncoprotein. As such, small molecule drugs targeting the catalytic center of
      JMJD2A might be useful in breast cancer adjuvant therapy.

PMID- 22948257
TI  - CO2 laser conditioning of porcelain surfaces for bonding metal orthodontic
      brackets.
AB  - Bonding to porcelain remains to be a challenge in orthodontic treatments. The
      objective of this study was to evaluate the effect of CO2 laser conditioning of
      porcelain surfaces on shear bond strength (SBS) of orthodontic brackets. Eighty
      feldspathic porcelain specimens were divided into four groups of 20. In each
      group, half of the porcelain surfaces were deglazed, while the others remained
      glazed. The specimens in groups 1 to 3 were treated with a fractional CO2 laser
      for 10 s using 10 mJ of energy, frequency of 200 Hz and powers of 10 W (group 1),
      15 W (group 2) and 20 W (group 3). In group 4, a 9.6 % hydrofluoric (HF) acid gel
      was used for 2 min. A silane coupling agent was applied before bracket bonding,
      and the SBS was measured with a universal testing machine after 24 h. Deglazing
      caused significant increase in SBS of laser treated porcelain surfaces (p <
      0.05), but had no significant effect on SBS when HF acid was used for etching (p
      = 0.137). ANOVA revealed no significant difference in SBS values of the study
      groups when glazed surfaces were compared (p = 0.269). However, a significant
      between group difference was found among the deglazed specimens (p < 0.001).
      Tukey test revealed that the bond strengths of 10 W and 15 W laser groups were
      significantly higher than that of the HF acid group (p < 0.05). Laser
      conditioning with a fractional CO2 laser can be recommended as a suitable
      alternative to hydrofluoric acid for deglazed feldspathic porcelain. 

PMID- 22948258
TI  - Superselective alpha-adrenergic blockers versus transurethral resection of the
      prostate: a prospective comparison of health-related quality of life outcome
      after treating patients with benign prostatic hyperplasia.
AB  - PURPOSE: We prospectively evaluated the impact of transurethral resection of the
      prostate (TURP) versus superselective alpha-adrenergic blocker treatment on
      health-related quality of life (HRQOL) in men with clinically diagnosed benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: A total of 219 patients with
      lower urinary tract symptoms (LUTS) caused by BPH were recruited in this study.
      Treatment modalities consisted of standard TURP (n = 104) and tamsulosin medical
      treatment (n = 115). HRQOL was assessed by SF-36-Item Health Survey 1.0. LUTS
      were estimated by The International Prostate Symptom Score. Patients' outcome 4
      weeks after treatment was compared to pre-treatment status and to that of the
      other group. Statistically significant changes in each HRQOL scale from baseline
      to follow-up period were investigated. RESULTS: Baseline characteristics were
      similar in both groups except for the duration of disease before treatment that
      was longer in TURP group. Both treatments resulted in statistically significant
      improvements from pre-treatment in all scales of QOL after 4 weeks, with no
      significant differences observed between the two groups. In medical treatment
      group, there was a significant association between higher educational level and
      better QOL in all 8 scales. Our outcomes revealed a significant decrease in the
      IPSS in both groups but this improvement was more evident in TURP group.
      CONCLUSION: All scales concerning HRQOL were favorably improved 4 weeks after
      both surgical and medical treatment, and no significant differences were observed
      between these two treatment modalities for patients with symptomatic BPH. This
      information may aid patients when deciding which treatment option to take.

PMID- 22948260
TI  - The role of the Maillard reaction in the formation of flavour compounds in dairy
      products--not only a deleterious reaction but also a rich source of flavour
      compounds.
AB  - Dairy products are heated both during processing and by consumers during food
      preparation; consumers place a high level of importance on flavour when assessing
      product acceptability. Of particular importance to the flavour of heated dairy
      products is the highly complex network of Maillard reactions. Much focus has been
      placed on the undesirable flavours generated through the Maillard reaction and
      how to minimise the formation of these flavours. However, beneficial flavours can
      also be formed by the Maillard reaction; dairy products, such as ghee, are formed
      by heating and are characterised by the unique flavour generated by this
      chemistry. This review looks at the Maillard reaction as a source of beneficial
      flavours for cooked dairy products and the application of models to the study of
      flavour formation in food systems. Models are typically used to study complex
      reactions in a simplified way; however, they are not always applicable to food
      systems.

PMID- 22948261
TI  - CB1 and CB2 receptor expression and promoter methylation in patients with
      cannabis dependence.
AB  - CB1 and CB2 receptors are influenced via exogenous and endogenous cannabinoids.
      To date, little is known regarding changes in receptor expression and methylation
      in THC (tetrahydrocannabinol) dependence. Therefore, the CB1 and CB2 receptor
      mRNA expression levels and promoter methylation status in the peripheral blood
      cells of 77 subjects (36 with THC dependence, 21 cigarette smokers and 20
      nonsmokers) were assessed by quantitative real-time PCR and methylation-specific
      PCR. There was a significant difference in CB1 receptor expression levels between
      the three groups (ANOVA, p < 0.001, d.f. = 2, F = 71.3). The mean promoter
      methylation (%) was significantly negatively correlated with CB1 receptor mRNA
      expression levels (Spearman's rho: r = -0.37; p = 0.002). Using a mixed general
      linear model, it was demonstrated that the CB1 mRNA expression (as the dependent
      variable) was associated with the satisfaction with life scale (SWLS) (r = 0.101;
      T = 2.8; p = 0.007), craving (as measured with the VAS; r = -0.023; T = -2.3; p =
      0.023) and the WHO-Assist Subscale for Cannabis consumption (r = -0.068; T = 
      2.4; p = 0.02). CB1 receptor expression levels and methylation status appear to
      be altered in subjects with THC dependence.

PMID- 22948262
TI  - Can the ICF osteoarthritis core set represent a future clinical tool in measuring
      functioning in persons with osteoarthritis undergoing hip and knee joint
      replacement?
AB  - OBJECTIVE: To determine the dimensionality, reliability, model fit, adequacy of
      the qualifier levels, response patterns across different factors, and targeting
      of the International Classification of Functioning, Disability and Health (ICF)
      osteoarthritis core set categories in people with osteoarthritis undergoing hip
      and knee arthroplasty. METHODS: The osteoarthritis core set was rated in 316
      persons with osteoarthritis who were either in the pre-operative or within one
      year post-operative stage. Rasch analyses were performed using the RUMM 2030
      program. RESULTS: Twelve of the 13 body functions categories and 13 of the 19
      activity and participation categories had good model fit. The qualifiers
      displayed disordered thresholds necessitating rescoring. There was uneven spread
      of ICF categories across the full range of the patients' scores indicating off-
      targeting. Subtest analysis of the reduced ICF categories of body functions and
      activity and participation showed that the two components could be integrated to
      form one measure. CONCLUSION: The results suggest that it is possible to measure
      functioning using a unidimensional construct based on ICF osteoarthritis core set
      categories of body functions and activity and participation in this population.
      However, omission of some categories and reduction in qualifier levels are
      necessary. Further studies are needed to determine whether better targeting is
      achieved, particularly during the pre-operative and during the sub-acute care
      period.

PMID- 22948263
TI  - A prospective evaluation of pulmonary, systemic and hepatic haemodynamics in HIV
      HCV-coinfected patients before and after antiviral therapy with pegylated
      interferon and ribavirin.
AB  - BACKGROUND: Patients coinfected with HIV and HCV are at risk for developing
      portal hypertension (PHT), hyperdynamic circulation and pulmonary arterial
      hypertension (PAH). Data on the influence of antiviral therapy with pegylated
      interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV) are limited. METHODS:
      Haemodynamic parameters, including hepatic venous pressure gradient (HVPG),
      pulmonary arterial pressure (PAP(mean)), cardiac output (CO) and systemic
      vascular resistance (SysVR), were prospectively evaluated before and after PEG
      IFN-alpha+RBV therapy in 80 HIV-HCV-coinfected patients. RESULTS: Baseline
      evaluation showed a mean HVPG of 4.7 mmHg, CO of 6.15 l/min and PAP(mean) of 14.8
      mmHg. PHT was present in 26% of patients, hyperdynamic circulation in 5% and PAH
      in 4%. Patients with advanced fibrosis (METAVIR stage F3/F4; n=32) had
      significantly higher CO (P=0.008), lower SysVR (P=0.035), higher PAP(mean)
      (P=0.018) and higher pulmonary vascular resistance (P=0.022) than patients with
      stage F0-F2 fibrosis (n=48). Both hyperdynamic circulation and PAH were
      significantly associated with liver stiffness, fibrosis stage and portal
      pressure; a non-significant trend was found for CD4(+) T-cell counts and HIV RNA
      levels. No significant changes in PAP(mean), CO and SysVR were observed after PEG
      IFN-alpha+RBV treatment, although a significant decrease in HVPG was noted in
      patients with HCV eradication (P=0.013). CONCLUSIONS: The overall prevalence of
      hyperdynamic circulation and PAH in HIV-HCV coinfection is low. Advanced
      fibrosis, increased liver stiffness, elevated portal pressure and probably CD4(+)
      T-cell count and HIV viraemia represent risk factors for hyperdynamic circulation
      and PAH. PHT is present in 26% of HIV-HCV-coinfected patients evaluated for
      antiviral therapy. Successful HCV eradication significantly decreases HVPG.

PMID- 22948264
TI  - Characterizing spontaneously reported cognitive complaints: the development and
      reliability of a classification instrument.
AB  - BACKGROUND: The characteristics and associated risks of spontaneously reported
      cognitive complaints have not been investigated due to the lack of a
      classification instrument. METHODS: In phase 1, a classification system with
      descriptive categories and cognitive domains was developed by experts through a
      modified Delphi technique. In phase 2, 180 elderly patients seeking medical
      attention for cognitive complaints provided free reports of their cognitive
      difficulties and each complaint was recorded verbatim. Three observers were asked
      to classify each complaint into a descriptive category. Perceived cognitive
      function was further characterized using the Memory Complaint Questionnaire (MAC
      Q). RESULTS: The patients reported 493 spontaneous complaints, with a range of 1
      6 complaints per patient and a mean of 2.7 (+/-1.3). The proportion of complaints
      that could be classified into a category by each of the three observers varied
      from 91.9% to 95.7%. Inter-observer agreement assessed using the kappa statistic
      varied from 0.79 to 1 for descriptive categories and 0.83 to 0.97 for domains.
      Compared with the MAC-Q, spontaneously reported complaints provided complementary
      information by avoiding the cueing effect provoked by the questionnaire. The
      total number of complaints and their occurrences in specific domains were
      associated with important sociodemographic and clinical factors, indicating that
      their meaning and associated risks need to be further investigated. CONCLUSION:
      The instrument developed in this study proved to be a practical tool for
      classifying the majority of spontaneously reported cognitive complaints with high
      reliability. Further studies are needed to investigate clinical usefulness of
      this approach.

PMID- 22948265
TI  - Measurement of plasma and intracellular concentrations of raltegravir in patients
      with HIV infection.
AB  - Paired plasma and intracellular samples were obtained from 12 HIV-infected adults
      taking raltegravir twice daily (b.i.d.), and after switching to once daily. With
      b.i.d. dosing, no plasma trough concentrations were below the IC95, in contrast
      to 33% for once daily dosing. Fifty percent of the once daily group had
      intracellular trough concentrations below the inhibitory concentration 95 (IC95),
      25% in the b.i.d. group. Lower plasma and intracellular concentrations may
      contribute to inferior virologic suppression rates observed with once daily
      raltegravir dosing.

PMID- 22948266
TI  - Differences between self-reported and electronically monitored adherence among
      patients receiving antiretroviral therapy in a resource-limited setting.
AB  - BACKGROUND: Measurement of adherence to antiretroviral therapy (ART) by patient
      self-report is common in resource-limited settings but widely believed to
      overstate actual adherence. The extent to which these measures overstate
      adherence has not been examined among a large patient population. METHODS: HIV
      infected adult patients in Kenya who initiated ART within the past 3 months were
      followed for 6 months. Adherence was measured by participants' self-reports of
      doses missed in the past 7 days during monthly clinic visits and by continuous
      Medication Event Monitoring System (MEMS) in participants' pill bottles. Seven
      day self-reported adherence was compared to 7-day MEMS adherence, 30-day MEMS
      adherence, and adherence more than 90% during each of the first 6 months.
      RESULTS: Self-reported and MEMS adherence measures were linked for 669
      participants. Mean 7-day self-reported adherence was 98.7% and mean 7-day MEMS
      adherence was 86.0%, a difference of 12.7% (P < 0.01). The difference between the
      two adherence measures increased over time due to a decline in 7-day MEMS
      adherence. However, patients with lower MEMS adherence were in fact more likely
      to self-report missed doses and the difference between self-reported and MEMS
      adherence was similar for each number of self-reported missed doses. When
      analysis was limited to patients who reported rarely or never removing multiple
      doses at the same time, mean difference was 10.5% (P < 0.01). CONCLUSION: There
      is a sizable and significant difference between self-reported and MEMS adherence.
      However, a strong relationship between the measures suggests that self-reported
      adherence is informative for clinical monitoring and program evaluation.

PMID- 22948268
TI  - Interleukin 21 augments the hepatitis B virus-specific CD8+ T-cell response in
      vitro in patients coinfected with HIV-1.
AB  - OBJECTIVES: Hepatitis B virus (HBV) and HIV-1 share similar transmission routes,
      therefore, coinfection with both viruses is frequently observed. In HIV-1
      infected patients reduced interleukin 21 (IL-21) serum levels have been reported,
      which may impair virus-specific CD8 T-cell responses. DESIGN: The HBV-specific
      CD8 T cells in patients with and without HIV-1 coinfection were analyzed cross
      sectionally and it was tested whether addition of IL-21 in vitro augments HBV
      specific CD8 T-cell responses. METHODS: Patients with persistent HBV
      monoinfection as well as HIV-1-positive patients with persistent or resolved HBV
      infection were studied. The IL-21 serum levels were determined by ELISA and the
      HBV-specific CD8 T-cell response was determined after antigen-specific expansion
      by intracellular staining of interferon gamma. RESULTS: The HBV-specific CD8 T
      cell response was significantly higher in HIV-1-negative patients compared with
      HIV-1-positive patients. Interestingly, within the HIV-1-positive group the
      magnitude of the response did not differ between patients with chronic or
      resolved HBV-infection. The IL-21 serum levels were significantly lower in the
      HIV-1-positive group. Importantly, addition of IL-21 in vitro significantly
      increased the HBV-specific CD8 T-cell response in HIV-1-positive patients,
      whereas there was no beneficial effect of IL-21 on cells from HBV-monoinfected
      patients. CONCLUSION: HIV-1 coinfection is associated with a decreased HBV
      specific CD8 T-cell response that can be partially rescued in vitro by addition
      of IL-21.

PMID- 22948267
TI  - Missed opportunities to prevent mother-to-child-transmission:  systematic review
      and meta-analysis.
AB  - OBJECTIVES: To determine magnitude and reasons of loss to program and poor
      antiretroviral prophylaxis coverage in prevention of mother-to-child transmission
      (PMTCT) programs in sub-Saharan Africa. DESIGN: Systematic review and meta
      analysis. METHODS: We searched PubMed and Embase databases for PMTCT studies in
      sub-Saharan Africa published between January 2002 and March 2012. Outcomes were
      the percentage of pregnant women tested for HIV, initiating antiretroviral
      prophylaxis, having a CD4 cell count measured, and initiating antiretroviral
      combination therapy (cART) if eligible. In children outcomes were early infant
      diagnosis for HIV, and cART initiation. We combined data using random-effects
      meta-analysis and identified predictors of uptake of interventions. RESULTS:
      Forty-four studies from 15 countries including 75,172 HIV-infected pregnant women
      were analyzed. HIV-testing uptake at antenatal care services was 94% [95%
      confidence intervals (CIs) 92-95%] for opt-out and 58% (95% CI 40-75%) for opt-in
      testing. Coverage with any antiretroviral prophylaxis was 70% (95% CI 64-76%) and
      62% (95% CI 50-73%) of pregnant women eligible for cART received treatment. Sixty
      four percent (95% CI 48-81%) of HIV exposed infants had early diagnosis performed
      and 55% (95% CI 36-74%) were tested between 12 and 18 months. Uptake of PMTCT
      interventions was improved if cART was provided at the antenatal clinic and if
      the male partner was involved. CONCLUSION: In sub-Saharan Africa, uptake of PMTCT
      interventions and early infant diagnosis is unsatisfactory. An integrated family
      centered approach seems to improve retention.

PMID- 22948269
TI  - Breast milk cellular HIV-specific interferon gamma responses are associated with
      protection from peripartum HIV transmission.
AB  - OBJECTIVE: Breast milk is a major route of infant HIV infection, yet the majority
      of breast-fed, HIV-exposed infants escape infection by unknown mechanisms. This
      study aimed to investigate the role of HIV-specific breast milk cells in
      preventing infant HIV infection. DESIGN: A prospective study was designed to
      measure associations between maternal breast milk HIV-specific interferon-gamma
      (IFN-gamma) responses and infant HIV-1 detection at 1 month of age. METHODS: In a
      Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-gamma
      ELISpot responses were measured. Logistic regression was used to measure
      associations between breast milk IFN-gamma responses and infant HIV infection at
      1 month of age. RESULTS: IFN-gamma responses were detected in breast milk from
      117 of 170 (69%) women. IFN-gamma responses were associated with breast milk
      viral load, levels of macrophage inflammatory protein (MIP) 1alpha, MIP-1beta,
      regulated upon activation, normal T-cell expressed, and secreted and stromal-cell
      derived factor 1 and subclinical mastitis. Univariate factors associated with
      infant HIV infection at 1 month postpartum included both detection and breadth of
      breast milk IFN-gamma response (P = 0.08, P = 0.04, respectively), breast milk
      MIP-1beta detection (P = 0.05), and plasma (P = 0.004) and breast milk (P =
      0.004) viral load. In multivariate analyses adjusting for breast milk viral load
      and MIP-1beta, breast milk IFN-gamma responses were associated with an
      approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR)
      0.29, 95% confidence interval (CI) 0.092-0.91], and each additional peptide pool
      targeted was associated with an approximately 35% reduction in infant HIV (aOR
      0.65, 95% CI 0.44-0.97). CONCLUSION: These data show breast milk HIV-gag-specific
      IFN-gamma cellular immune responses are prevalent and may contribute to
      protection from early HIV transmission. More broadly, these data suggest breast
      milk cellular responses are potentially influential in decreasing mother-to-child
      transmission of viruses.

PMID- 22948270
TI  - Role of antiretroviral therapy in improving food security among patients
      initiating HIV treatment and care.
AB  - OBJECTIVE: Although the physical health benefits of HIV antiretroviral therapy
      (ART) are well documented, the socioeconomic benefits are still being
      established. Few studies have examined the effects of ART on food insecurity,
      although studies suggest there may be a benefit via improved health and ability
      to work. DESIGN: Twelve-month prospective cohort study of 602 treatment-naive
      patients initiating clinical care in Uganda. METHODS: Longitudinal multivariate
      logistic regression was used to investigate the effect of ART on food insecurity
      compared to HIV care without ART. A staged regression approach was used to
      explore pathways through which ART may affect food insecurity. RESULTS: Food
      insecurity decreased significantly for both the ART and non-ART groups over time,
      with the ART group experiencing greater reductions by the end of the study. ART
      remained a significant predictor of reduction in food insecurity over time after
      controlling for baseline differences in the regression model (odds ratio 0.642; P
      < 0.01). Improvements in work and mental health status were identified as
      potential pathways through which ART may improve food security. CONCLUSION: Taken
      together with the well known benefits of food security on ART adherence,
      treatment retention and clinical outcomes in resource-poor settings, our results
      suggest that a positive feedback loop of improved functioning and productivity
      could result from the interaction between food security and ART. Policymakers
      could leverage this positive cycle by strengthening mental health support and
      promoting sustainable food security interventions as part of HIV treatment
      programs.

PMID- 22948271
TI  - Male sex and the risk of mortality among individuals enrolled in antiretroviral
      therapy programs in Africa:  a systematic review and meta-analysis.
AB  - BACKGROUND: HIV/AIDS has historically had a sex and gender-focused approach to
      prevention and care. Some evidence suggests that HIV-positive men have worse
      treatment outcomes than their women counterparts in Africa. METHODS: We conducted
      a systematic review and meta-analysis of the effect of sex on the risk of death
      among participants enrolled in antiretroviral therapy (ART) programs in Africa
      since the rapid scale-up of ART. We included all cohort studies evaluating the
      effect of sex (male, female) on the risk of death among participants enrolled in
      regional and national ART programs in Africa. We identified these studies by
      searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird
      random-effects method to pool the proportions of men receiving ART and the hazard
      ratios for death by sex. RESULTS: Twenty-three cohort studies, including 216 008
      participants (79 892 men) contributed to our analysis. The pooled proportion of
      men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled
      hazard ratio estimate indicated a significant increase in the risk of death for
      men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was
      consistent across sensitivity analyses. INTERPRETATION: The proportion of men
      enrolled in ART programs in Africa is lower than women. Additionally, there is an
      increased risk of death for men enrolled in ART programs. Solutions that aid in
      reducing these sex inequities are needed.

PMID- 22948272
TI  - The protease inhibitor atazanavir triggers autophagy and mitophagy in human
      preadipocytes.
AB  - BACKGROUND: The association between HAART and lipodystrophy is well established,
      but lipodystrophy pathogenesis is still poorly understood. Drugs, and in
      particular protease inhibitors, accumulate in adipose tissue affecting adipocyte
      physiology and gene expression by several mechanisms. Recent studies have
      identified autophagy as another process affected by these classes of drugs, but
      no studies have been performed in adipose cells. METHODS: SW872 preadipocytic
      human cell line was used to evaluate changes induced by amprenavir (APV),
      ritonavir (RTV), or atazanavir (ATV), all used at 10-200 MUmol/l. A subline was
      stably transfected with murine stem cell virus (pMSCV)-enhanced green fluorescent
      protein (EGFP)-LC3 plasmid (to obtain a fluorescent LC3 protein) and treated with
      ATV at different doses. The distribution of LC3 and the colocalization of
      mitochondria, lysosome, and autophagosome were assessed by confocal microscopy.
      Transmission electron microscopy of ATV-treated cells was also performed. The
      cellular content of lysosomes was assessed using Lysotracker Green; apoptosis was
      evaluated by annexin V/propidium iodide staining, and mitochondrial superoxide
      anion (mtO2) was analyzed by mitoSOX red. Lysosomes, apoptosis, and mtO2 were
      studied by flow cytometry and multispectral imaging flow cytometry. RESULTS: In
      SW872 cells, RTV caused massive apoptosis, more than autophagy, whereas APV was
      almost ineffective. ATV induced both apoptosis (high doses) and autophagy (low
      doses). ATV-treated cells displayed LC3-specific punctae, suggesting the
      formation of autophagosomes that enclosed mitochondria, as revealed by electron
      microscopy. At low doses, ATV promoted mitochondrial superoxide generation,
      whereas at high doses, it induced mitochondrial membrane depolarization.
      CONCLUSION: Autophagy/mitophagy can be considered a mechanism triggered by ATV in
      SW872 preadipocytes.

PMID- 22948273
TI  - Cervicovaginal HIV-1-neutralizing immunoglobulin A detected among HIV-1-exposed
      seronegative female partners in HIV-1-discordant couples.
AB  - OBJECTIVE: Cervicovaginal HIV-1-neutralizing immunoglobulin A (IgA) was
      associated with reduced HIV-1 acquisition in a cohort of commercial sex workers.
      We aimed to define the prevalence and correlates of HIV-1-neutralizing IgA from
      HIV-1-exposed seronegative (HESN) women in HIV-1-serodiscordant relationships.
      METHODS: HIV-1-serodiscordant couples in Nairobi were enrolled and followed
      quarterly up to 2 years, and women in concordant HIV-1-negative relationships
      were enrolled as controls. Cervicovaginal, seminal, and blood samples were
      collected at enrollment and follow-up. Cervicovaginal IgA was assessed for HIV-1
      neutralizing activity by a peripheral blood mononuclear cell-based assay using an
      HIV-1 clade A primary isolate. RESULTS: HESN women in discordant relationships
      had significantly more HIV-1-neutralizing IgA detected in genital secretions
      compared with control women [36 of 155 (23%) vs. four of 70 (6%), respectively;
      odds ratio (OR) 5.0; 95% confidence interval (CI) 1.70-14.64; P = 0.003]. These
      responses persisted over time in all available follow-up cervicovaginal samples
      from women with detectable HIV-1-neutralizing IgA at baseline. Partner median HIV
      1 plasma viral load was lower among women who had HIV-1-neutralizing IgA compared
      with women without detectable activity (4.3 vs. 4.8 log(10) copies/ml,
      respectively; OR 0.70; 95% CI 0.51-0.94; P = 0.02). A similar trend was found
      with partner seminal viral load (OR 0.57; 95% CI 0.32-1.02; P = 0.06).
      CONCLUSION: HESN women were five times more likely to have neutralizing IgA in
      cervicovaginal secretions than low-risk control women, and these responses were
      inversely associated with partner viral load. These observations support the
      existence of antiviral activity in the mucosal IgA fraction following sexual HIV
      1 exposure.

PMID- 22948274
TI  - Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS)
      following the 2008 WHO classification.
AB  - Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The
      WHO classification offers prognostic information and helps with the treatment
      decisions. However, morphological changes are subject to potential inter-observer
      variance. The aim of our study was to explore the reliability of the 2008 WHO
      classification of MDS, reviewing 100 samples previously diagnosed with MDS using
      the 2001 WHO criteria. Specimens were collected from 10 hospitals and were
      evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20
      samples, and each sample was analyzed independently by two morphologists. The
      second observer was blinded to the clinical and laboratory data, except for the
      peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS
      (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the
      2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered
      suitable (27 %). Although there were a high number of observers taking part, the
      rate of discordance was quite similar among the five pairs. The inter-observer
      concordance was very good regarding refractory anemia with excess blasts type 1
      (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good
      regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74
      %). However, the categories with unilineage dysplasia were not reproducible in
      most of the cases. The rate of concordance with refractory cytopenia with
      unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring
      sideroblasts (two of eight). Our results show that the 2008 WHO classification
      gives a more accurate stratification of MDS but also illustrates the difficulty
      in diagnosing MDS with unilineage dysplasia.

PMID- 22948275
TI  - Meeting report: 7th Fabisch Symposium for Cancer Research and Molecular Cell
      Biology--regulated intramembrane proteolysis in cancer development and
      neurodegenerative diseases.

PMID- 22948276
TI  - Leveraging EHR data for outcomes and comparative effectiveness research in
      oncology.
AB  - Along with the increasing adoption of electronic health records (EHRs) are
      expectations that data collected within EHRs will be readily available for
      outcomes and comparative effectiveness research. Yet the ability to effectively
      share and reuse data depends on implementing and configuring EHRs with these
      goals in mind from the beginning. Data sharing and integration must be planned
      both locally as well as nationally. The rich data transmission and semantic
      infrastructure developed by the National Cancer Institute (NCI) for research
      provides an excellent example of moving beyond paper-based paradigms and
      exploiting the power of semantically robust, network-based systems, and engaging
      both domain and informatics expertise. Similar efforts are required to address
      current challenges in sharing EHR data.

PMID- 22948277
TI  - Ovarian cancer: advances in first-line treatment strategies with a particular
      focus on anti-angiogenic agents.
AB  - Ovarian cancer is an important health concern worldwide. The majority of patients
      present with advanced disease, and despite initial chemosensitivity, most relapse
      and die from their disease. Better therapeutic options are urgently required.
      Maximal surgical debulking in combination with platinum/taxane chemotherapy has
      been the standard of care in advanced ovarian cancer since the mid-1990s. Trials
      investigating the addition of a third chemotherapeutic agent have disappointingly
      failed to demonstrate benefit. Intra-peritoneal therapy demonstrated improvements
      in outcomes in some trials, but at the cost of increased toxicity and
      inconvenience. Encouragingly, prospective data has now demonstrated benefits with
      bevacizumab in both the first-line and relapsed settings; however, interpretation
      is complex, particularly considering recent data demonstrating non-inferiority of
      neo-adjuvant chemotherapy with delayed primary surgery, and other data
      demonstrating a substantial improvement in outcome as a result of first-line
      paclitaxel dose fractionation. This article reviews the recent advances in
      ovarian cancer treatment and discusses current management and key areas for
      future research.

PMID- 22948278
TI  - Maternal effects in the highly communal sociable weaver may exacerbate brood
      reduction and prepare offspring for a competitive social environment.
AB  - Maternal effects can influence offspring phenotype with short- and long-term
      consequences. Yet, how the social environment may influence egg composition is
      not well understood. Here, we investigate how laying order and social environment
      predict maternal effects in the sociable weaver, Philetairus socius, a species
      that lives in massive communal nests which may be occupied by only a few to 100+
      individuals in a single nest. This range of social environments is associated
      with variation in a number of phenotypic and life-history traits. We investigate
      whether maternal effects are adjusted accordingly. We found no evidence for the
      prediction that females might benefit from modifying brood hierarchies through an
      increased deposition of androgens with laying order. Instead, females appear to
      exacerbate brood reduction by decreasing the costly production of yolk mass and
      antioxidants with laying order. Additionally, we found that this effect did not
      depend on colony size. Finally, in accordance with an expected increased
      intensity of environmental stress with increasing colony size, we found that yolk
      androgen concentration increased with colony size. This result suggests that
      females may enhance the competitive ability of offspring raised in larger
      colonies, possibly preparing the offspring for a competitive social environment.

PMID- 22948279
TI  - Root morphology and architecture respond to N addition in Pinus tabuliformis,
      west China.
AB  - Belowground dynamics of terrestrial ecosystems are responding to global increases
      in anthropogenic N deposition with important consequences for productivity and
      ecosystem health. We compared root characteristics across five root orders in
      Pinus tabuliformis plantations treated for 3 years to a gradient of N addition (0
      15 g m(-2) year(-1)). In reference plots, the roots of P. tabuliformis were finer
      and with higher specific root length than reported for other pine species,
      suggesting severe N limitation. Addition of N resulted in slightly reduced fine
      root biomass and significant changes in root morphology, responses that were
      associated primarily with first and second order roots. In particular, root
      number, cumulative root length, individual root length, and specific root length
      all declined with increasing N addition for first and second order roots, with
      most of the responses elicited at <9 g m(-2) year(-1) N addition. These responses
      (1) support the concept of ephemeral root modules consisting of first and second
      orders and (2) are consistent with a change in functional demand from uptake to
      transport with increasing soil resource availability. Traditionally, fine roots
      have been identified by a somewhat arbitrary diameter cut-off (e.g., 1 or 2 mm);
      as an index of fine root function, diameter would fail to reveal most of the
      functional response.

PMID- 22948280
TI  - Impact of long-term cinacalcet, ibandronate or teriparatide therapy on bone
      mineral density of hemodialysis patients: a pilot study.
AB  - BACKGROUND: Insufficient evidenced-based information is available for the
      treatment of osteoporosis in hemodialysis (HD) patients. METHODS: In 102 HD
      patients, bone mineral density (BMD) was measured twice 16 +/- 3 months apart. In
      the second BMD measurement 66 of them had a femoral neck (FN) T-score <-2.5. Of
      these 66 patients, 38 consented to a bone biopsy. Depending on both the bone
      biopsy findings and parathyroid hormone levels, patients were assigned to
      treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml
      received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received
      ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild
      abnormalities received no treatment. A third BMD measurement was done after an
      average treatment period of 13-16 months. We compared the annual percent change
      of FN and lumbar spine (LS) BMD before and during treatment. RESULTS: FN and LS
      BMD decreased significantly in the cinacalcet group, with an annual change of 3.6
      and 3.4% before treatment to -4.2% (p = 0.04) and -7.7% (p = 0.02) during
      treatment, respectively. In the teriparatide group, FN and LS BMD increased,
      although not significantly, with an annual change of -5.4 and -2.6% before
      treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate
      and the no treatment groups, BMD change rate remained negative during the whole
      study. CONCLUSIONS: Teriparatide administration improved BMD in HD patients with
      adynamic bone disease, although these results did not reach statistical
      significance. In HD patients with osteitis fibrosa, ibandronate did not improve
      BMD while cinacalcet reduced BMD.

PMID- 22948281
TI  - Attitudes of long-term care staff toward dementia and their related factors.
AB  - BACKGROUND: Attitudes of residential care staff toward residents with dementia
      affect the quality of care. We examined the attitude of frontline residential
      care staff toward residents with dementia, and how the presence of specialized
      care units or programs may affect staff attitude. METHODS: Staff working in
      nursing homes participated in a survey which covered demographic data, current
      state of dementia care in workplace, opinion regarding dementia care, and
      perceived importance of dementia behaviors. RESULTS: 1,047 nurses and personal
      care workers participated. 78.8% respondents reported difficulties in managing
      dementia residents. Those who ranked positive symptoms as more important were 4.5
      times more likely to report difficulties, independent of experience. Independent
      factors associated with positive attitudes toward further training were working
      in a non-profit home (OR 2.4, 95% CI 1.1, 5.0; p = 0.024) and having a dementia
      program or unit in the current workplace (OR 1.8, 95% CI 0.985, 3.302; p =
      0.056). Only having a dementia program or unit in the current workplace was
      associated with a positive attitude toward commitment to stay in dementia care
      (OR 1.9, 95% CI 1.1, 3.2; p = 0.021), adjusted for gender, type of home, post,
      dementia prevalence in workplace, and work experience. CONCLUSION: The majority
      of long-term care staff felt dementia care difficult yet hold positive attitude
      toward further training and were committed to stay in dementia care. Having a
      specialized dementia care unit or program in the current workplace was associated
      with commitment to stay in dementia care and was marginally associated with
      positive attitude toward further training.

PMID- 22948282
TI  - Adrenal cortex disorders: hormones out of kilter.

PMID- 22948283
TI  - Transduced wild-type but not P301S mutated human tau shows hyperphosphorylation
      in transgenic mice overexpressing A30P mutated human alpha-synuclein.
AB  - Neuropathological and cell culture studies suggest that tau and alpha-synuclein
      pathologies may promote each other. To study the relevance and functional
      implications of these findings in vivo, we transduced hippocampal neurons of wild
      type or human A30P alpha-synuclein transgenic mice with wild-type or P301S
      mutated human tau using an adeno-associated virus vector. Green fluorescent
      protein transduction was used as a control. We assessed spontaneous exploratory
      activity, anxiety and spatial learning and memory 11 weeks after the transduction
      and perfused the mice for histology. The transduced tau was mainly found in axon
      terminals and largely restricted within the hippocampi. In addition, neurons
      around the injection site showed cytoplasmic staining for human tau in both wild
      type and A30P mice. Of these tau-positive neurons, 44% in A30P mice but only 3%
      in wild-type mice receiving human wild-type tau transduction formed paired
      helical filament-1 (PHF-1)-positive cytoplasmic densities. In contrast, only 1%
      of tau-positive neurons were also PHF-1 positive after transduction with P301S
      tau in mice of either genotype. Transduction of P301S tau reduced swimming speed
      but otherwise tau transduction had no significant behavioral consequences.
      Cytoplasmic PHF-1 densities were associated with poor spatial memory in wild-type
      mice but slightly improved memory in A30P mice, indicating that also tau
      hyperphosphorylation does not necessarily compromise neural functions. These data
      demonstrate that alpha-synuclein promotes tau hyperphosphorylation depending on
      the amino acids on the 301 site. 

PMID- 22948284
TI  - The comparison of cognitive and functional performance in children and
      Alzheimer's disease supports the retrogenesis model.
AB  - The retrogenesis model states that the progression of brain aging and Alzheimer's
      disease (AD) deterioration proceeds inversely to human ontogenic acquisition
      patterns. Our aim was to assess if the progressive decline of cognitive abilities
      and functional capacity in AD follows an inverse sequence of acquisition compared
      to normal developmental patterns. One hundred eighty one children ranging in age
      from 4 to 12 years and 148 adults (cognitively normal, subjects with mild
      cognitive impairment, and mild-moderately severe AD) were assessed with the same
      cognitive and functional tools. The statistical analyses showed a progressive and
      inverse distribution on cognitive, functional, and mental age scores when
      comparing results of children classified by chronological age and patients by
      dementia staging. The pattern of cognitive acquisition in children showed a
      progressive development of overall cognitive function along all age ranges, in
      addition to a simultaneous acquisition of instrumental and basic daily living
      activities in the functional domain. AD patients showed a progressive decline in
      cognitive and functional domains, which concurs with the sequence of impairment
      reported in this dementia. Our findings provide support to the inverse and
      progressive pattern of functional and cognitive decline observed in AD patients
      compared to the developmental acquisition of these capacities in children, as
      stated by the retrogenesis model. Nonetheless, certain differences should be
      considered when comparing the sequence of acquisition during ontogenic
      development with that of progressive loss during the course of AD. Retrogenesis
      may account for the progressive loss of neocortical-related functions in AD.

PMID- 22948285
TI  - A theoretical investigation of the interaction between small Pd particles and 1
      butyl-3-methyl imidazolium ionic liquids with Cl-, BF4(-) and PF6(-) anions.
AB  - Density functional calculations have been used to investigate the interaction
      between Pd(n) clusters (n = 1-6) and 1-butyl-3-methylimidazolium (Bmim(+)) based
      ionic liquids (ILs) with the anions [Cl(-)], [BF(4)(-)] and [PF(6)(-)]. The
      interaction of small Pd(n) clusters (1 <= n <= 6) with a single cation or anion
      is also studied. The interaction strengths in anion-Pd(n) categories with n = 1-6
      follow the trend [Cl(-)] > [BF(4)(-)] > [PF(6)(-)]. The cation could also form
      interactions with Pd(n) clusters. Compared with a single anion or cation, the
      interaction could be strengthened when palladium particles interact with the
      whole ion pair. Further studies indicated that anionPd interaction is the
      decisive factor in the interaction between the Pd atom and the whole ion pair.
      The Pd(2) dimer interacts with the whole ion pair much more strongly than the Pd
      atom. Solvent effects have been considered in the present study by means of the
      polarizable continuum model. It is found that the stability of [Bmim(+).BF(4)(-)]
      Pd(n) and [Bmim(+).PF(6)(-)]-Pd(n) complexes with n = 1 and 2 can be improved in
      solvents.

PMID- 22948286
TI  - Nodular lesions on post-surgical scars: scar sarcoidosis.

PMID- 22948287
TI  - Secreted factors from human mast cells trigger inflammatory cytokine production
      by human airway smooth muscle cells.
AB  - BACKGROUND: A notable feature of allergic asthma is the infiltration of mast
      cells into smooth muscle in the human airway. Thus, mast cells and human airway
      smooth muscle (hASM) cells are likely to exhibit mutual functional modulation via
      direct cell-cell contact or through released factors. This study examined mast
      cell modulation of hASM cell cytokine release. METHODS: The mast cell line
      HMCalpha was used to model mast cell function. hASM cells were either co-cultured
      directly with resting or IgE/antigen-stimulated HMCalpha cells or treated with
      HMCalpha-conditioned media to examine the impact on cytokine release. The
      activation pathways triggered in hASM cells by the mast cell-derived factors were
      examined through the use of selective inhibitors and by Western blotting.
      RESULTS: HMCalpha cells, or their conditioned media, induced the expression of
      cytokines (IL-8 and IL-6) by hASM cells at both the mRNA and the protein level.
      Cytokine expression in hASM cells was greatly amplified when HMCalpha cells were
      IgE/antigen-activated. The effects of the conditioned media were not mediated by
      the chemokines MCP-1 and MIP-1alpha or by exosomes. While the mast cell-derived
      factor(s) increased p38(MAPK) phosphorylation in hASM cells, cytokine production
      was not inhibited by the p38(MAPK) inhibitor SB203580. hASM cell production of IL
      8 induced by HMCalpha condition media but not IL-6 was, however, attenuated by
      the Src tyrosine kinase inhibitor PP2. CONCLUSIONS: Our study shows that the
      release of soluble mediators by activated mast cells can stimulate hASM cells to
      elicit production of proinflammatory cytokines that may then exacerbate airway
      inflammation in asthma.

PMID- 22948288
TI  - Use of multivariate indicator kriging methods for assessing groundwater
      contamination extents for irrigation.
AB  - Multivariate geostatistical approaches have been applied extensively in
      characterizing risks and uncertainty of pollutant concentrations exceeding
      anthropogenic regulatory limits. Spatially delineating an extent of contamination
      potential is considerably critical for regional groundwater resources protection
      and utilization. This study used multivariate indicator kriging (MVIK) to
      determine spatial patterns of contamination extents in groundwater for irrigation
      and made a predicted comparison between two types of MVIK, including MVIK of
      multiplying indicator variables (MVIK-M) and of averaging indicator variables
      (MVIK-A). A cross-validation procedure was adopted to examine the performance of
      predicted errors, and various probability thresholds used to calculate ratios of
      declared pollution area to total area were explored for the two MVIK methods. The
      assessed results reveal that the northern and central aquifers have excellent
      groundwater quality for irrigation use. Results obtained through a cross
      validation procedure indicate that MVIK-M is more robust than MVIK-A.
      Furthermore, a low ratio of declared pollution area to total area in MVIK-A may
      result in an unrealistic and unreliable probability used to determine extents of
      pollutants. Therefore, this study suggests using MVIK-M to probabilistically
      determine extents of pollutants in groundwater.

PMID- 22948289
TI  - Spatial variability of soil total and DTPA-extractable cadmium caused by long
      term application of phosphate fertilizers, crop rotation, and soil
      characteristics.
AB  - Increasing cadmium (Cd) accumulation in agricultural soils is undesirable due to
      its hazardous influences on human health. Thus, having more information on
      spatial variability of Cd and factors effective to increase its content on the
      cultivated soils is very important. Phosphate fertilizers are main contamination
      source of cadmium (Cd) in cultivated soils. Also, crop rotation is a critical
      management practice which can alter soil Cd content. This study was conducted to
      evaluate the effects of long-term consumption of the phosphate fertilizers, crop
      rotations, and soil characteristics on spatial variability of two soil Cd species
      (i.e., total and diethylene triamine pentaacetic acid (DTPA) extractable) in
      agricultural soils. The study was conducted in wheat farms of Khuzestan Province,
      Iran. Long-term (27-year period (1980 to 2006)) data including the rate and the
      type of phosphate fertilizers application, the respective area, and the rotation
      type of different regions were used. Afterwards, soil Cd content (total or DTPA
      extractable) and its spatial variability in study area (400,000 ha) were
      determined by sampling from soils of 255 fields. The results showed that the
      consumption rate of di-ammonium phosphate fertilizer have been varied enormously
      in the period study. The application rate of phosphorus fertilizers was very high
      in some subregions with have extensive agricultural activities (more than 95
      kg/ha). The average and maximum contents of total Cd in the study region were
      obtained as 1.47 and 2.19 mg/kg and DTPA-extractable Cd as 0.084 and 0.35 mg/kg,
      respectively. The spatial variability of Cd indicated that total and DTPA
      extractable Cd contents were over 0.8 and 0.1 mg/kg in 95 and 25 % of samples,
      respectively. The spherical model enjoys the best fitting and lowest error rate
      to appraise the Cd content. Comparing the phosphate fertilizer consumption rate
      with spatial variability of the soil cadmium (both total and DTPA extractable)
      revealed the high correlation between the consumption rate of P fertilizers and
      soil Cd content. Rotation type was likely the main effective factor on variations
      of the soil DTPA-extractable Cd contents in some parts (eastern part of study
      region) and could explain some Cd variation. Total Cd concentrations had
      significant correlation with the total neutralizing value (p < 0.01), available P
      (p < 0.01), cation exchange capacity (p < 0.05), and organic carbon (p < 0.05)
      variables. The DTPA-extractable Cd had significant correlation with OC (p <
      0.01), pH, and clay content (p < 0.05). Therefore, consumption rate of the
      phosphate fertilizers and crop rotation are important factors on solubility and
      hence spatial variability of Cd content in agricultural soils.

PMID- 22948290
TI  - A pilot study to assess inflammatory biomarker changes when raltegravir is added
      to a virologically suppressive HAART regimen in HIV-1-infected patients with
      limited immunological responses.
AB  - BACKGROUND: Despite successful suppression of HIV-1 with HAART, some patients do
      not have robust immunological recovery. Chronic inflammation from persistent
      immune activation could contribute to this poor response, resulting in HIV-1
      disease progression and the development of some non-HIV-1 comorbidities. METHODS:
      We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral
      loads and poor CD4(+) T-cell responses on long-term stable HAART to assess
      whether the addition of raltegravir would have an effect on biomarkers of chronic
      inflammation. A total of 26 patients were followed for 1 year on the intensified
      regimen. In addition to T-cell responses, we evaluated changes in activated
      CD4(+) and CD8(+) T-cells, several pro-inflammatory cytokines and chemokines and
      memory cell responses to HIV-1-associated peptides. RESULTS: Although there was
      no improvement in CD4(+) T-cell counts, the percentage change in CD4(+)%,
      CD4(+)/CD8(+) ratios and RANTES (regulated on activation normal T-cells expressed
      and secreted) increased significantly while the percentage change in CD8(+) T
      cell counts and CD8(+)%, activated CD4(+) T-cells and several pro-inflammatory
      chemokines and cytokines decreased significantly. The percentage change in HIV-1
      specific nef, pol set 1, gag and env memory T-cells also declined. CONCLUSIONS:
      The addition of raltegravir to a virologically suppressive HAART regimen in
      patients with poor immunological responses resulted in the reduction of several
      pro-inflammatory biomarkers; increases were seen in RANTES levels and
      CD4(+)/CD8(+) T-cell ratios. The clinical relevance of these observations is
      beyond the scope of this study.

PMID- 22948296
TI  - [Skin infections caused by Fusarium].
AB  - Under favorable conditions even molds can cause skin infections. Fusarium spp.
      belong to this group of agents. Onychomycoses due to Fusarium spp. are regularly
      encountered and cannot be clinically distinguished from nail infections triggered
      by dermatophytes. They can occur in otherwise healthy persons. Skin lesions
      caused by Fusarium spp. may be necrotizing, ulcerating, pustular, vasculitis
      like, panniculitis-like or granulomatous. Single lesions can develop after fungal
      inoculation into damaged tissue; multiple ones are often due to a septic
      dissemination of Fusarium in severely immunocompromised patients. An immediate
      verification of the agents can be life-saving in such cases. Pathogenic Fusarium
      spp. should be identified at the species level and need to be tested for their
      susceptibility to antimycotics. In case of multiple lesions, systemic therapy is
      required. Many strains of Fusarium spp. are susceptible to amphotericin B,
      voriconazole and posaconazole; itraconazole and terbinafine may be helpful in
      certain cases.

PMID- 22948297
TI  - Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer.
AB  - AZ64 is a novel antitumor agent designed as a tropomyosin-related kinase (Trk)
      inhibitor; however, its effect on lung cancer and its mechanism of action remain
      unclear. This study aimed to elucidate the antitumor activity of AZ64 and its
      mechanism of action against non-small cell lung cancer (NSCLC). Our results
      demonstrate that AZ64 has a potent anti-proliferative effect on NSCLC cells and
      acts in a dose- and time-dependent manner. We also demonstrate that AZ64
      suppresses the anchorage-independent growth and invasion of NSCLC cells. In vivo
      experiments demonstrated that AZ64 significantly reduced the tumor growth of
      NSCLC xenografts in nude mice and was well-tolerated. Mechanistic experiments
      revealed that AZ64 induced the G2/M arrest of NSCLC cells by the accumulation of
      phospho-cdc2 (Tyr15) at the G2/M transition, following the downregulation of
      Cdc25C expression. Collectively, our data demonstrate that AZ64 is a potential
      antitumor drug that may be used for the treatment of NSCLC, which functions by
      targeting the G2/M transition via the inhibition of the dephosphorylation of
      phospho-cdc2 (Tyr15).

PMID- 22948299
TI  - Risk and protective factors associated with gay neighborhood residence.
AB  - Using a sample of 482 ethnically diverse current substance using men who have sex
      with men who reported recent unprotected anal intercourse, this study compared
      health risk behaviors-substance use and sexual HIV risk-and one health protective
      factor-prosocial activities-between men who live in a gay neighborhood and those
      who do not. Data are drawn from comprehensive health and social risk assessments
      administered in South Florida. In a multivariate logistic regression model,
      methamphetamine use, high rates of receptive unprotected anal intercourse, and
      lower levels of prosocial engagement were found to be risk factors associated
      with gay neighborhood residence. Compared with living elsewhere, gay neighborhood
      residence appeared to be protective against cocaine use and substance dependence.
      Implications of the findings for prevention interventions are discussed, as is
      the need for further research regarding decisions about neighborhood residence
      and how neighborhood risk and protective factors emerge and are sustained.

PMID- 22948298
TI  - CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in
      cultured vascular smooth muscle cells.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is the most common hereditary vascular dementia
      caused by mutations in NOTCH3 gene. Pathology is manifested in small- and middle
      sized arteries throughout the body, though primarily in cerebral white matter.
      Hemodynamics is altered in CADASIL and NOTCH3 is suggested to regulate actin
      filament polymerization and thereby vascular tone. We analyzed NOTCH3 expression
      and morphology of actin cytoskeleton in genetically genuine cultured human
      CADASIL vascular smooth muscle cells (VSMCs) (including a cell line homozygous
      for p.Arg133Cys mutation) derived from different organs, and in control VSMCs
      with short hairpin RNA (shRNA)-silenced NOTCH3. NOTCH3 protein level was higher
      in VSMCs derived from adult than newborn arteries in both CADASIL and control
      VSMCs. CADASIL VSMCs showed altered actin cytoskeleton including increased
      branching and node formation, and more numerous and smaller adhesion sites than
      control VSMCs. Alterations in actin cytoskeleton in shRNA-silenced VSMCs were
      similar as in CADASIL VSMCs. Severity of the alterations in actin filaments
      corresponded to NOTCH3 expression level being most severe in VSMCs derived from
      adult cerebral arteries. These observations suggest that hypomorphic NOTCH3
      activity causes alterations in actin organization in CADASIL. Furthermore,
      arteries from different organs have specific characteristics, which modify the
      effects of the NOTCH3 mutation and which is one explanation for the exceptional
      susceptibility of cerebral white matter arteries.

PMID- 22948300
TI  - Farming, reported pesticide use, and prostate cancer.
AB  - Prostate cancer is the leading cancer type diagnosed in American men and is the
      second leading cancer diagnosed in men worldwide. Although studies have been
      conducted to investigate the association between prostate cancer and exposure to
      pesticides and/or farming, the results have been inconsistent. We performed a
      meta-analysis to summarize the association of farming and prostate cancer. The
      PubMed database was searched to identify all published case-control studies that
      evaluated farming as an occupational exposure by questionnaire or interview and
      prostate cancer. Ten published and two unpublished studies were included in this
      analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were
      almost four times more likely to be farmers compared with controls with benign
      prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence
      interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results
      were obtained when non-BPH controls were considered, but with moderate
      heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p
      value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide
      exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95%
      CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with
      exposure to fertilizers was observed. Our findings confirm that farming is a risk
      factor for prostate cancer, but this increased risk may not be due to exposure to
      pesticides.

PMID- 22948302
TI  - First Brazilian position on resistant hypertension.

PMID- 22948303
TI  - The diagnosis of left ventricular outflow tract obstruction in hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a prevalent genetic disease characterized by left
      ventricular hypertrophy, presenting dynamic obstruction of outflow tract with
      subaortic gradient happening at rest in 30% of the cases. It is attributed to the
      intricate interaction between the anterior mitral leaflet, the interventricular
      septum and altered flow vectors generated in left ventricle along with changes in
      outflow tract geometry. Mitral regurgitation in varying degrees is found with or
      without association with structural deformities of the valve apparatus. The
      exercise echocardiogram evidences latent obstruction easily induced by exercise
      in 60 to 75% of non-obstructive forms. The determination of the gradient under
      this condition must be considered in routine investigation of patients with mild
      or no obstruction at rest. The evaluation of hypertrophic cardiomyopathy
      incorporates methods based on the ultrasound image, which, along with MRI, allow
      recognizing ventricular obstruction generating mechanisms, thus facilitating the
      diagnosis and management of obstructive and latent obstructive forms.

PMID- 22948304
TI  - Comments on the article by Araujo: are the criteria for peer review and
      publication clear?

PMID- 22948305
TI  - Case 5/2012: six-year-old child with anomalous origin of left coronary artery and
      mitral regurgitation.

PMID- 22948306
TI  - Latent obstructive hypertrophic cardiomyopathy: is echocardiography enough?

PMID- 22948307
TI  - Occlusion of post-myocardial infarction ventricular defect with prosthesis CERA.

PMID- 22948308
TI  - Co-expression of AtbHLH17 and AtWRKY28 confers resistance to abiotic stress in
      Arabidopsis.
AB  - Stress adaptation in plants involves altered expression of many genes through
      complex signaling pathways. To achieve the optimum expression of downstream
      functional genes, we expressed AtbHLH17 (AtAIB) and AtWRKY28 TFs which are known
      to be upregulated under drought and oxidative stress, respectively in
      Arabidopsis. Multigene expression cassette with these two TFs and reporter gene
      GUS was developed using modified gateway cloning strategy. The GUS assay and
      expression analysis of transgenes in transgenic plants confirmed the integration
      of multigene cassette. The transgenic lines exhibited enhanced tolerance to NaCl,
      Mannitol and oxidative stress. Under mannitol stress condition significantly
      higher root growth was observed in transgenics. Growth under stress and recovery
      growth was substantially superior in transgenics exposed to gradual long term
      desiccation stress conditions. We demonstrate the expression of several
      downstream target genes under various stress conditions. A few genes having
      either WRKY or bHLH cis elements in their promoter regions showed higher
      transcript levels than wild type. However, the genes which did not have either of
      the motifs did not differ in their expression levels in stress conditions
      compared to wild type plants. Hence co-expressing two or more TFs may result in
      upregulation of many downstream target genes and substantially improve the stress
      tolerance of the plants.

PMID- 22948309
TI  - Integration, stability and expression of the E. coli phytase transgene in the
      Cassie line of Yorkshire EnviropigTM.
AB  - The genomic structure and generational stability of the transgene carried by the
      Cassie (CA) line of the transgenic EnviropigTM, a prospective food animal, are
      reported here. This transgene is composed of the Escherichia coli phytase coding
      sequence regulated by the mouse parotid secretory protein promoter to direct
      secretion of phytase in the saliva. In the CA line the transgene integrated in
      chromosome 4 is present as a concatemer of three copies, two in a head to tail
      orientation and the third in a reverse orientation 3' to the other copies with a
      6 kbp deletion in the 5' promoter region. The overall size of the integrated
      transgene complex is 46 kbp. During integration a 66 kbp segment of the
      chromosome was deleted, but a BLAST search of the segment from a GenBank clone
      did not reveal any essential genes. The transgene integration site was stable
      through 9 generations analyzed. Phytase activity in the saliva was similar among
      11 day old hemizygous boars and gilts and remained relatively constant through
      nine generations of hemizygous pigs. However, as the pigs grew there generally
      was a gradual decrease in activity that stabilized when pigs reached the finisher
      phase of growth (4-6 months old). Homozygous pigs exhibited 1.5 fold higher
      phytase activity (P < 0.0001) than that of hemizygous littermates. Moreover, no
      differential salivary phytase activity was seen in hemizygotes arising from CA
      Yorkshire and CA-Duroc breed outcrosses, suggesting that expression of the
      transgene is unaffected by genetic background. This data demonstrates that an
      exogenous phytase gene can be stably transmitted and expressed in the salivary
      glands of a domestic food animal.

PMID- 22948310
TI  - Molecular discriminators using single wall carbon nanotubes.
AB  - The interaction between single wall carbon nanotubes (SWNTs) and amphiphilic
      molecules has been studied in a solid phase. SWNTs are allowed to interact with
      different amphiphilic probes (e.g. lipids) in a narrow capillary interface.
      Contact between strong hydrophobic and amphiphilic interfaces leads to a
      molecular restructuring of the lipids at the interface. The geometry of the
      diffusion front and the rate and the extent of diffusion of the interface are
      dependent on the structure of the lipid at the interface. Lecithin having a
      linear tail showed greater mobility of the interface as compared to a branched
      tail lipid like dipalmitoyl phosphatidylcholine, indicating the hydrophobic
      interaction between single wall carbon nanotube core and the hydrophobic tail of
      the lipid. Solid phase interactions between SWNT and lipids can thus become a
      very simple but efficient means of discriminating amphiphilic molecules in
      general and lipids in particular.

PMID- 22948311
TI  - In vitro analysis of the role of replication protein A (RPA) and RPA
      phosphorylation in ATR-mediated checkpoint signaling.
AB  - Replication protein A (RPA) plays essential roles in DNA metabolism, including
      replication, checkpoint, and repair. Recently, we described an in vitro system in
      which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia
      mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here,
      we report that phosphorylation of other ATR targets, p53 and Rad17, has the same
      requirements and that RPA is also phosphorylated in this system. At high p53 or
      Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA
      with phosphomimetic mutations cannot support ATR kinase function, whereas a non
      phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR
      substrates depends on the recruitment of ATR and the substrates by RPA to the RPA
      ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit
      essentially normal activity in nucleotide excision repair, revealing RPA
      separation of function for checkpoint and excision repair.

PMID- 22948313
TI  - Novel physiological properties of ethanol extracts from Eremurus chinensis
      Fedtsch. roots: in vitro antioxidant and anticancer activities.
AB  - Eremurus chinensis Fedtch. (ECF) with nutritious roots, belonging to the genus of
      Eremurus, is a special species grown in China. However, the functional properties
      of ECF roots have not been intensely investigated. The antioxidant and anticancer
      effects of ethanol extracts from E. chinensis Fedtch. roots (ECFE) were evaluated
      in the present study. ECFE exhibited high radical-scavenging activities on DPPH
      and ABTS radicals, strong reducing power and Fe(2+)-chelating activity. ECFE also
      effectively protected biological macromolecules including proteins, lipids and
      DNA against oxidative damage induced by Cu(2+)/H(2)O(2) and AAPH systems.
      Moreover, the MTT assay revealed that ECFE inhibited proliferation of HepG2 cells
      in a dose- and time-dependent manner. Western blot analysis demonstrated that
      treatment with ECFE led to cell apoptosis hallmarked by PARP cleavage.
      Additionally, caspase-3 activation, cytochrome C (Cyt-C) release and increase of
      Bax/Bcl-2 ratio suggested that mitochondria-mediated signaling pathway might be
      involved in ECFE-induced apoptosis in HepG2 cells. These results demonstrate the
      remarkable potentiality of ECFE as a valuable source of antioxidants which
      possess original anticancer abilities.

PMID- 22948312
TI  - A properly configured ring structure is critical for the function of the
      mitochondrial DNA recombination protein, Mgm101.
AB  - Mgm101 is a Rad52-type recombination protein of bacteriophage origin required for
      the repair and maintenance of mitochondrial DNA (mtDNA). It forms large
      oligomeric rings of ~14-fold symmetry that catalyze the annealing of single
      stranded DNAs in vitro. In this study, we investigated the structural elements
      that contribute to this distinctive higher order structural organization and
      examined its functional implications. A pair of vicinal cysteines, Cys-216 and
      Cys-217, was found to be essential for mtDNA maintenance. Mutations to the polar
      serine, the negatively charged aspartic and glutamic acids, and the hydrophobic
      amino acid alanine all destabilize mtDNA in vivo. The alanine mutants have an
      increased propensity of forming macroscopic filaments. In contrast, mutations to
      aspartic acid drastically destabilize the protein and result in unstructured
      aggregates with severely reduced DNA binding activity. Interestingly, the serine
      mutants partially disassemble the Mgm101 rings into smaller oligomers. In the
      case of the C216S mutant, a moderate increase in DNA binding activity was
      observed. By using small angle x-ray scattering analysis, we found that Mgm101
      forms rings of ~200 A diameter in solution, consistent with the structure
      previously established by transmission electron microscopy. We also found that
      the C216A/C217A double mutant tends to form broken rings, which likely provide
      free ends for seeding the growth of the super-stable but functionally defective
      filaments. Taken together, our data underscore the importance of a delicately
      maintained ring structure critical for Mgm101 activity. We discuss a potential
      role of Cys-216 and Cys-217 in regulating Mgm101 function and the repair of
      damaged mtDNA under stress conditions.

PMID- 22948314
TI  - Gender and rapid alterations of hemispheric dominance during planning.
AB  - BACKGROUND: Mental planning and carrying out a plan provoke specific cerebral
      hemodynamic responses. Gender aspects of hemispheric laterality using rapid
      cerebral hemodynamics have not been reported. METHOD: Here, we applied functional
      transcranial Doppler sonography to examine lateralization of cerebral
      hemodynamics of the middle cerebral arteries of 28 subjects (14 women and 14 men)
      performing a standard planning task. There were easy and difficult problems, and
      mental planning without motor activity was separated from movement execution.
      RESULTS: Difficult mental planning elicited lateralization to the right
      hemisphere after 2 or more seconds, a feature that was not observed during
      movement execution. In females, there was a dominance to the left hemisphere
      during movement execution. Optimized problem solving yielded an increased
      laterality change to the right during mental planning. CONCLUSIONS: Gender
      related hemispheric dominance appears to be condition-dependent, and change of
      laterality to the right may play a role in optimized performance. Results are of
      relevance when considering laterality from a perspective of performance
      enhancement of higher cognitive functions, and also of psychiatric disorders with
      cognitive dysfunctions and abnormal lateralization patterns such as
      schizophrenia.

PMID- 22948315
TI  - Affective decision-making is predictive of three-month relapse in polysubstance
      dependent alcoholics.
AB  - BACKGROUND/AIMS: Common and long-lasting deficits in decision-making in
      polysubstance-dependent alcoholics (PSA) reflect neurobiological alterations that
      define the chronic nature of addiction. These deficits affect goal-directed
      behavior and might be critical risk factors predicting relapse in PSA. METHODS:
      The Delay Discounting Task (DDT) and the Iowa Gambling Task (IGT) assessed the
      delay-discounting and decision-making skills among 37 abstinent PSA. RESULTS: The
      findings indicated that IGT but not DDT performances were associated with 3-month
      abstinence, irrespective of the influence of personality traits and coexistent
      medications. CONCLUSION: The results show that the IGT, which assesses processes
      that are important in the latter stages of addiction, is ecologically more valid
      compared to the DDT, which assesses processes important in the early stages. They
      underline the importance of using neurocognitive measures to identify high
      relapse risk patients and emphasize the relevance of promoting new treatments.

PMID- 22948316
TI  - Evaluation of postoperative nephrolithiasis and renal dysfunction in gastric
      cancer patients.
AB  - BACKGROUND: Roux-en-Y (R-Y) gastric bypass, also known as bariatric surgery,
      sometimes causes postoperative hyperoxaluria and subsequent oxalate
      nephrolithiasis in obese patients. In this study, we retrospectively investigated
      the frequency of occurrence of nephrolithiasis and renal dysfunction in
      postoperative gastric cancer patients with respect to the surgical procedures
      employed. METHODS: Two hundred and twenty-six consecutive gastric cancer
      patients, who underwent distal gastrectomy with Billroth-I reconstruction (DGBI,
      60 patients), distal gastrectomy with R-Y reconstruction (DGRY, 81 patients), and
      total gastrectomy with R-Y reconstruction (TGRY, 85 patients), were investigated
      for postoperative nephrolithiasis and renal dysfunction. We also examined the
      risk factors for postoperative nephrolithiasis in these patients with gastric
      cancer. RESULTS: Nephrolithiasis was detected in 3 (5%), 7 (9%), and 21 (25%)
      patients in the DGBI, DGRY, and TGRY groups, respectively. There were significant
      differences in the frequency of nephrolithiasis between the DGBI and TGRY groups
      (p = 0.004), and between the DGRY and TGRY groups (p = 0.011), but there was no
      significant difference between the DGBI and DGRY groups. Multivariate logistic
      regression analysis revealed that gender and extent of gastrectomy were
      independent risk factors associated with nephrolithiasis. Renal dysfunction was
      found in 5 patients (6%) in the TGRY group, but was not found in either the DGBI
      or the DGRY group. Nephrolithiasis was detected in all these 5 patients, and a
      renal biopsy performed in one patient revealed the presence of intratubular
      calcium oxalate crystals with chronic tubulointerstitial nephritis. CONCLUSION:
      Total gastrectomy with R-Y reconstruction was an independent predictive factor
      for nephrolithiasis in patients with gastric cancer.

PMID- 22948317
TI  - The Cholegas Study: safety of prophylactic cholecystectomy during gastrectomy for
      cancer: preliminary results of a multicentric randomized clinical trial.
AB  - BACKGROUND: Cholelithiasis is more frequent in patients after gastrectomy, due to
      dissection of vagal branches and gastrointestinal reconstruction. METHODS: A
      randomized controlled trial was conducted from November 2008 to March 2012.
      Patients were randomized into two groups: prophylactic cholecystectomy (PC) and
      standard gastric surgery only (SS) for curable cancers. We planned three end
      points: evaluation of the number of patients who developed symptoms and needed
      further surgery for cholelithiasis after standard gastric cancer surgery,
      evaluation of the incidence of cholelithiasis overall after standard gastric
      cancer surgery and perioperative complications or costs of prophylactic
      cholecystectomy. The present study answers to the last end point only. RESULTS:
      After 40 months from the beginning of study, 172 patients were eligible from 9
      Centers. Ten patients refused consent and 32 were excluded due to flawing of
      inclusion criteria (not confirmed adenocarcinomas and no R0 surgery). Therefore,
      final analysis included 130 patients: 65 in PC group and 65 in SS. Among PC
      group, 12 patients had surgical complications during the perioperative period;
      only 1 biliary leakage, conservatively treated, might have been caused by
      prophylactic cholecystectomy. 6 patients had surgical complications in SS group.
      One postoperative death occurred in PC group due to pulmonary embolism.
      Differences were not statistically significant. Similarly, no differences were
      significant in duration of surgery, blood loss, hospital stay. CONCLUSIONS:
      Concomitant cholecystectomy during standard surgery for gastric malignancies
      seemed to add no extra perioperative morbidity, mortality and costs to the sample
      included in the study.

PMID- 22948318
TI  - Epidemiology and cultural differences in tension-type headache.
AB  - Tension-type headache (TTH) is the most prevalent headache worldwide Stovner et
      al. (Cephalalgia 27:193-210, 2007**); Robbins and Lipton (Semin Neurol 30:107-19,
      2010**); Jensen and Stovner (Lancet Neurol 7:354-361, 2008). Despite being the
      most prevalent primary headache type, there is still a relative lack of
      epidemiologic data when compared to that for migraine Robbins and Lipton (Semin
      Neurol 30:107-19, 2010**). Out of the available data, it is apparent that there
      are wide variations and differences in tension-type headache epidemiology across
      different cultures Stovner et al. (Cephalalgia 27:193-210, 2007**). This review
      will focus on reviewing and comparing the epidemiology of episodic and chronic
      TTH in adult populations across varying continental regions. This will include
      prevalence, cultural variations and differences in study methodologies, common
      precipitants and prognosis. Possible explanations for such widely varying
      prevalence rates among different cultures and regions will also be discussed.

PMID- 22948319
TI  - Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after
      rituximab for refractory nephrotic syndrome.
AB  - BACKGROUND: Rituximab, an anti-CD20 antibody that targets B cells, is a promising
      agent against steroid-dependent and steroid-resistant nephrotic syndrome in
      children. CASE-DIAGNOSIS/TREATMENT: We report a 3-year-old boy who presented with
      atypical Pneumocystis jiroveci pneumonia (PCP) following administration of
      rituximab for refractory nephrotic syndrome. He had received cyclosporine and
      daily prednisolone for over 1 year. Following rituximab therapy, a hazy shadow
      was observed on his chest X-ray. Chest-computed tomography revealed multiple
      nodular lesions in bilateral lungs, although his clinical symptoms were subtle.
      PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar
      lavage. Lung wedge resection of the nodular lesion exhibited granulomas
      containing a few cysts of P. jiroveci that primarily consisted of T cells and
      histiocytes and lacked B cells. A deficiency of B cells following rituximab
      treatment suggests a dramatic effect on the immune response and, therefore, could
      result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an
      emerging concept previously reported in adults with hematological disease, bone
      marrow transplant, or treatment with rituximab. We report the first pediatric
      case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover,
      bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci
      DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully
      recovered with sulfamethoxazole/trimethoprim treatment because of early
      detection. CONCLUSIONS: The indication of rituximab for refractory nephrotic
      syndrome has increased recently. Therefore, recognition of the risk of atypical
      PCP is important. Our findings suggest that PCP prophylaxis should be considered
      following rituximab therapy.

PMID- 22948320
TI  - Growth hormone treatment after renal transplantation: a promising but underused
      chance to improve growth.
AB  - Growth retardation remains a clinical problem in children with chronic kidney
      disease (CKD) prior to and during end-stage renal disease. The growth of
      approximately 40 % of children on dialysis is stunted. Even so, growth hormone
      treatment (GH) is not used in the majority of small children prior to
      transplantation. Also, GH is effective in improving growth after transplantation,
      but again, it is only rarely used in this situation mainly for fear of triggering
      rejection episodes. In controlled studies, the number of patients who developed
      rejection episodes with GH was no greater than the number in untreated controls.
      However, patients with prior frequent rejection episodes developed further
      repeated subsequent rejection episodes. Many patients with repeated rejection
      episodes before GH treatment have reduced renal function and are expected to
      proceed to dialysis or retransplantation. We believe that in these patients,
      early individual decisions for or against GH treatment should be made as soon as
      other treatment strategies, such as steroid withdrawal, have failed or are not
      indicated. Decisions for GH treatment at a later pubertal age come too late for
      significant growth response and/or improvement of final height.

PMID- 22948321
TI  - Evaluation of a new elderly trauma triage algorithm.
AB  - OBJECTIVES: Undertriage is common in patients 55 years and older and is even
      worse for those 65 and older. In 1999, the Florida legislature implemented a
      statewide trauma system, including a new Florida trauma triage algorithm (FTTA).
      This study examines how the new system affected prehospital triage in younger
      versus older patients. METHODS: A retrospective review of appropriate triage was
      conducted at a regional level 2 trauma center during a 1-year period. Patients
      were considered to have major trauma if they were FTTA positive or had an Injury
      Severity Score (ISS) of >= 16. An internal trauma review panel examined hospital
      discharge data to assess triage accuracy. Odds ratios (ORs) and confidence
      intervals (CIs) were calculated. RESULTS: A total of 49% of nontrauma patients 15
      to 54 years old were seen at the trauma center compared with 83% of FTTA positive
      and 86% of patients with an ISS >= 16 (OR 2.88, 95% CI 2.44-3.41). For those with
      an ISS >= 16, the OR was 6.53 (95% CI 4.07-10.47). For patients 55 years and
      older, 52% of nontrauma patients were triaged to the trauma center versus 59% of
      FTTA positive and 64% of patients with ISS >= 16 (OR 1.03, 95% CI 0.93-1.15).
      Patients 55 years and older with an ISS >= 16 had only a slightly increased
      triage effect (OR 1.67, 95% CI 1.08-2.58) compared with those with an ISS 0 to 15
      (OR 1.00, 95% CI 0.89-1.12). CONCLUSIONS: Whereas FTTA appropriately triaged
      patients 15 to 54 years old to the trauma center, those 55 years old and older
      were much less likely to be triaged correctly. The reasons for this finding
      remain unknown, and further studies are needed to investigate and improve elderly
      triage.

PMID- 22948322
TI  - Propagation of uncertainty in Bayesian diagnostic test interpretation.
AB  - OBJECTIVES: Bayesian interpretation of diagnostic test results usually involves
      point estimates of the pretest probability and the likelihood ratio corresponding
      to the test result; however, it may be more appropriate in clinical situations to
      consider instead a range of possible values to express uncertainty in the
      estimates of these parameters. We thus sought to demonstrate how uncertainty in
      sensitivity, specificity, and disease pretest probability can be accommodated in
      Bayesian interpretation of diagnostic testing. METHODS: We investigated three
      questions: How does uncertainty in the likelihood ratio propagate to the posttest
      probability range, assuming a point estimate of pretest probability? How does
      uncertainty in the sensitivity and specificity of a test affect uncertainty in
      the likelihood ratio? How does uncertainty propagate when present in both the
      pretest probability and the likelihood ratio? RESULTS: Propagation of likelihood
      ratio uncertainty depends on the pretest probability and is more prominent for
      unexpected test results. Uncertainty in sensitivity and specificity propagates
      into the calculation of likelihood ratio prominently as these parameters approach
      100%; even modest errors of +/- 10% caused dramatic propagation. Combining errors
      of +/- 20% in the pretest probability and in the likelihood ratio exhibited
      modest propagation to posttest probability, suggesting a realistic target range
      for clinical estimations. CONCLUSIONS: The results provide a framework for
      incorporating ranges of uncertainty into Bayesian reasoning. Although point
      estimates simplify the implementation of Bayesian reasoning, it is important to
      recognize the implications of error propagation when ranges are considered in
      this multistep process.

PMID- 22948323
TI  - Commentary on "propagation of uncertainty in bayesian diagnostic test
      interpretation".

PMID- 22948324
TI  - Resident preferences for a curriculum in healthcare transitions for young adults.
AB  - OBJECTIVES: Numerous national groups recognize that healthcare providers should
      be trained to care for patients with special healthcare needs who are
      transitioning from pediatric to adult health care, yet there is little emphasis
      on this training in most residency programs. The survey discussed here assessed
      resident preferences for a curriculum that addresses healthcare transitions for
      young adults. METHODS: Trainees in primary care residency programs at three
      institutions in South Carolina were surveyed. Residents were asked about their
      preferences for timing and modality of transition education and desire to see
      patients older/younger than dictated by training. Residents also ranked topics of
      transition by level of need/interest. Comparison of responses was analyzed via t
      tests and the Fisher exact test. RESULTS: Respondents (n = 84) represented three
      institutions and eight training programs. Eighty percent of residents prefer that
      a curriculum be continuous throughout training and include clinical experiences
      (79%), case discussions (60%), and lectures/didactics (56%). Pediatric residents
      were more likely than were internal medicine residents to value seeing patients
      older/younger than their program dictates (84% vs 42%; P < 0.01). Internal
      medicine residents were more likely than pediatric residents to rank as high
      need/interest "medical knowledge of pediatric disease persisting into adulthood"
      (77% vs 47%; P= 0.05) and "caring for adult-aged patients reliant on caregivers"
      (53% vs 9%; P < 0.01). CONCLUSIONS: Residents prefer a healthcare transition
      curriculum that is continuous throughout residency and uses combined modalities
      for topic presentation. Residents training in different disciplines have varied
      levels of need/interest for transition-related topics and this should direct the
      development of healthcare transition curricula.

PMID- 22948325
TI  - Commentary on "resident preferences for a curriculum in healthcare transitions
      for young adults".

PMID- 22948326
TI  - Making sense of state health data: the case of Kentucky.
AB  - OBJECTIVE: State health rankings present oversimplified and potentially damaging
      accounts of health status. Using the example of Kentucky, this article
      illustrates the realities masked by rankings that use averages and fail to
      account for social determinants of health. METHODS: Findings from a range of
      publicly available data are combined to shed light on factors that influence or
      are associated with health status indicators, including demographic data, health
      services utilization, health system elements, poverty, and educational
      attainment. RESULTS: Despite its low overall performance, Kentucky includes
      counties with health status that is equal to the highest-ranking states. Poverty
      and loss of healthy, working-age populations are closely associated with low
      health status, as are low rates of high school graduation. CONCLUSIONS: Rankings
      that average health status indicators across widely diverse areas may yield
      findings that are only marginally relevant for health policy development. A high
      burden of morbidity pulls resources from population health to high-cost health
      services, challenging the viability of long-range initiatives; however, a
      comprehensive approach to health status improvement will be necessary to bring
      more southern US states like Kentucky into higher-ranking positions.

PMID- 22948327
TI  - Fever, abnormal white blood cell count, neutrophilia, and elevated serum C
      reactive protein in adult hospitalized patients with bacteremia.
AB  - OBJECTIVES: Relatively little is known about the prevalence of and factors
      associated with the absence of fever, normal white blood cell count (WBC), lack
      of neutrophilia, and the frequency of elevated serum C-reactive protein (CRP) in
      adult hospitalized patients with bacteremia. METHODS: Frequencies of fever
      (temperature >= 100 degrees F), abnormal WBC count (>= 10,000/MUL or <4500/MUL),
      neutrophilia (neutrophils >= 80%) and potential factors that may be associated
      with negative results, and frequency of elevated serum CRP were studied
      retrospectively in 622 bacteremic episodes in adult patients at a community
      teaching hospital. RESULTS: The frequencies of individual parameters were as
      follows: fever, 78.4% (95% confidence interval [CI] 74.9%-81.6%); abnormal WBC
      count, 65.2% (95% CI 61.3%-69.0%); neutrophilia, 67.5% (95% CI 63.7%-71.2%); and
      elevated CRP (>0.8 mg/dL), 98.4% (95% CI 97%-99.2%). Age 50 years and older,
      corticosteroid use, and isolation of either Staphylococcus sp not aureus or
      Enterococcus sp combined were independently associated with the absence of fever
      (P <= 0.01 for all). Isolation of Staphylococcus sp not aureus/Enterococcus and
      lack of corticosteroid use were independently associated with normal WBC (P <
      0.05 for both). Nonwhite race and primary bacteremia were independently
      associated with lack of neutrophilia (P < 0.05 for both). CONCLUSIONS: Absence of
      fever, normal WBC, and lack of neutrophilia are common in patients with
      bacteremia and may be confounded by a variety of factors; however, serum CRP
      remains elevated in the majority (>98%) of bacteremic episodes.

PMID- 22948328
TI  - Current concepts and management strategies in chronic kidney disease-mineral and
      bone disorder.
AB  - The term renal osteodystrophy describes the pathological changes in bone
      structure in chronic kidney disease (CKD); however, this term fails to describe
      adequately the adverse changes in mineral and hormonal metabolism in CKD that
      have grave consequences for patient survival. CKD-mineral and bone disorder (CKD
      MBD) is a broader, newly defined term that should be used instead of renal
      osteodystrophy to define the mineral, bone, hormonal, and calcific cardiovascular
      abnormalities that are seen in CKD. The new paradigm in the management of renal
      bone disease is to "think beyond the bones" and strive to improve cardiovascular
      outcomes and survival. This means treating other aspects of the disease process
      that go beyond merely controlling parathyroid hormone levels. Primary physicians
      need to take a proactive approach to the management of CKD-MBD because the
      disorder begins early in the course of CKD, well before a patient is referred to
      a nephrologist. This review outlines the evidence behind the understanding of CKD
      MBD, its implications for overall mortality, and the latest recommendations for
      management of CKD-MBD in patients with predialysis CKD.

PMID- 22948329
TI  - Using music interventions in perioperative care.
AB  - Anxiety and pain are common responses to surgery, and both can negatively affect
      patient outcomes. Music interventions have been suggested as a nonpharmacological
      intervention to alleviate pain and anxiety during surgical treatment. Although
      the data are somewhat mixed, the research suggests that music-based interventions
      are effective in reducing anxiety, pain perception, and sedative intake. The
      majority of studies have focused on interventions during the postoperative period
      and address pain reduction, with preoperative use of music targeting anxiety
      reduction the second most commonly cited objective. Most of the studies found in
      the literature involve passive music listening via headphones. The data suggest
      that researcher-selected music is most effective in reducing anxiety, primarily
      because it incorporates evidence-based parameters such as consistent tempo and
      dynamics, stable rhythms, and smooth melodic lines. Finally, the literature
      suggests that music therapists can serve as experts to help medical personnel
      identify effective implementation strategies.

PMID- 22948330
TI  - Make eye contact, sit down, and touch your patient.

PMID- 22948331
TI  - Wise but difficult choices.

PMID- 22948332
TI  - Long-term outcome of preoperative disrupted inner/outer segment junctions
      assessed using spectral-domain optical coherence tomography in patients with
      idiopathic epiretinal membrane.
AB  - PURPOSE: To evaluate the anatomic and functional outcomes as assessed by spectral
      domain optical coherence tomography in patients with a preoperative disrupted or
      irregular photoreceptor inner/outer segment (IS/OS) junction who underwent
      idiopathic epiretinal membrane (ERM) surgery and were followed for at least 2
      years. METHODS: We retrospectively studied all of the patients with idiopathic
      ERM who had a preoperative disrupted IS/OS junction and were scheduled to undergo
      a transconjunctival 25-gauge vitrectomy between September 2007 and October 2009.
      All of the patients who had a 2-year or longer follow-up period were included in
      the study. The best-corrected visual acuity (BCVA) and structural changes in the
      IS/OS junction were examined before and 3, 6, 12, and 24 months after surgery.
      Furthermore, patients were divided into two groups based on whether the
      preoperative disrupted IS/OS junction had been caused by a lamellar macular hole
      (LMH type) or swelling as a result of ERM traction (S type). Morphologic changes
      in the IS/OS junctions of each type were also investigated. RESULTS: A total of
      17 patients were identified in this study. Overall, a significantly better
      postoperative BCVA was seen after surgery; in particular, the BCVA at 24 months
      was significantly better than that at 12 months (p=0.018). Although the disrupted
      IS/OS junction appeared normal in 1 out of 17 eyes at 12 months, 7 eyes appeared
      normal at 24 months. These 7 eyes showed significant postoperative improvement in
      BCVA compared with the remaining 10 eyes (p=0.045, p=0.021, p=0.019, and p=0.015
      at 3, 6, 12, and 24 months, respectively). The preoperative disrupted IS/OS
      junction was classified as LMH type in 8 eyes and as S type in 9 eyes. The LMH
      type, rather than the S type, tended to show a persistently disrupted IS/OS
      junction at 24 months, although the difference was not significant. CONCLUSION:
      Anatomic and functional recovery of preoperative disrupted IS/OS junctions can be
      acquired even after more than 1 year postoperatively. However, eyes with
      persistent irregularities of the IS/OS junction at a 2-year follow-up, especially
      those with LMH type irregularities, might have a limited visual improvement.

PMID- 22948333
TI  - Metabolic effects of intraoperative amino acid infusion in mongrel dogs.
AB  - BACKGROUND: Intraoperative amino acid infusion can attenuate the decrease in core
      temperature, but the metabolic effects are uncertain. METHODS: Thirty-six healthy
      mongrel dogs undergoing ileectomy under general anesthesia were infused
      intraoperatively with normal saline or 18 compound amino acids at 6, 12, and 24
      kJ.kg-1.h-1 (NS, 6-, 12-, and 24-kJ groups) and studied until 24 h after the
      operation. Blood glucose, plasma insulin, free fatty acids, and triglyceride
      concentrations were determined at 7 defined time points. Muscle aminograms,
      urinary urea, and 3-methylhistidine excretions were measured before and after the
      operation. RESULTS: Blood glucose and plasma insulin increased amino acid dose
      dependently during the operation and in the early period after the operation.
      Free fatty acids were significantly lower in the 12- and 24-kJ groups compared
      with the NS group at the end of the operation. The negative nitrogen balance was
      alleviated dose dependently in the amino acid groups on operation day. The
      urinary 3-methylhistidine decreased significantly during the first 24 h after the
      operation in the 24-kJ group, while it increased in the other groups with the
      largest increase in the NS group. Basic, branched-chain, and aromatic amino acids
      in the vastus lateralis muscle increased dose dependently at the end of the
      operation in the amino acid groups. CONCLUSION: Intraoperative amino acid
      infusion has the dose-dependent effects of increasing blood glucose, inhibiting
      fat mobilization and muscle protein breakdown.

PMID- 22948334
TI  - Evolutionary history of exon shuffling.
AB  - Exon shuffling has been characterized as one of the major evolutionary forces
      shaping both the genome and the proteome of eukaryotes. This mechanism was
      particularly important in the creation of multidomain proteins during animal
      evolution, bringing a number of functional genetic novelties. Here, genome
      information from a variety of eukaryotic species was used to address several
      issues related to the evolutionary history of exon shuffling. By comparing all
      protein sequences within each species, we were able to characterize exon
      shuffling signatures throughout metazoans. Intron phase (the position of the
      intron regarding the codon) and exon symmetry (the pattern of flanking introns
      for a given exon or block of adjacent exons) were features used to evaluate exon
      shuffling. We confirmed previous observations that exon shuffling mediated by
      phase 1 introns (1-1 exon shuffling) is the predominant kind in multicellular
      animals. Evidence is provided that such pattern was achieved since the early
      steps of animal evolution, supported by a detectable presence of 1-1 shuffling
      units in Trichoplax adhaerens and a considerable prevalence of them in
      Nematostella vectensis. In contrast, Monosiga brevicollis, one of the closest
      relatives of metazoans, and Arabidopsis thaliana, showed no evidence of 1-1 exon
      or domain shuffling above what it would be expected by chance. Instead, exon
      shuffling events are less abundant and predominantly mediated by phase 0 introns
      (0-0 exon shuffling) in those non-metazoan species. Moreover, an intermediate
      pattern of 1-1 and 0-0 exon shuffling was observed for the placozoan T.
      adhaerens, a primitive animal. Finally, characterization of flanking intron
      phases around domain borders allowed us to identify a common set of symmetric 1-1
      domains that have been shuffled throughout the metazoan lineage.

PMID- 22948336
TI  - Gynaecologic cancer symptom awareness, concern and care seeking among US women: a
      multi-site qualitative study.
AB  - BACKGROUND: With limited screening options, early detection of gynaecologic
      cancers can depend on women recognizing the potential significance of symptoms
      and seeking care. OBJECTIVE: We investigated women's concern about symptoms that
      might be related to gynaecologic cancers, the underlying conditions they
      associated with symptoms and their actual and hypothetical response to symptoms.
      METHODS: Fifteen focus groups with women aged 40-60 years were conducted in
      Chicago, Los Angeles, Miami and New York City. Participants were given an
      untitled list of symptoms that could indicate various gynaecologic cancers and
      asked if any would concern them, what could cause each and what they would do if
      they experienced any of them. RESULTS: Overall, participants expressed greater
      concern about symptoms clearly gynaecologic in nature than other symptoms.
      Participants generally did not associate symptoms with any form of cancer. Some
      women who had experienced symptoms reported waiting an extended period before
      seeking care or not seeking care at all. The belief that a symptom indicated a
      benign condition was the most common reason given for delaying or foregoing care
      seeking. Strategies participants reported using to supplement or replace
      consultations with health care providers included Internet research and self
      care. CONCLUSION: Raising awareness of symptoms that can indicate gynaecologic
      cancers may lead to earlier detection and improved survival. In particular, women
      should be informed that gynaecologic cancers can cause symptoms that may not seem
      related to the reproductive organs (e.g. back pain) and that unusual vaginal
      bleeding should prompt them to seek care immediately.

PMID- 22948338
TI  - Risk assessment of Hymenoptera re-sting frequency: implications for decision
      making in venom immunotherapy.
AB  - BACKGROUND: Venom immunotherapy is highly efficacious in preventing anaphylactic
      sting reactions. However, there is an ongoing discussion regarding patient
      selection and whether and how to apply a cost-benefit analysis of venom
      immunotherapy. In order to help decision-making, we investigated the re-sting
      frequency of hymenoptera-venom-allergic patients to single out those at high
      risk. METHODS: In this retrospective study, re-sting data of 96 bee-venom
      allergic patients and 95 vespid-venom-allergic patients living mainly in a rural
      area of Switzerland were analyzed. Hymenoptera venom allergy status was rated
      according to the classification system of H.L. Mueller [J Asthma Res 1966;3:331
      333]. Different risk-groups were defined according to sting exposure and their
      median sting-free interval was calculated. RESULTS: The risk factors for a wasp
      or bee re-sting were outdoor occupation, beekeeping and habitation close to a bee
      house. Half of all vespid-venom-allergic outdoor workers were re-stung within
      3.75 years compared to 7.5 years for indoor workers. Similarly, 50% of the bee
      venom-allergic beekeepers or subjects with a bee-house in the vicinity suffered a
      bee re-sting within 5.25 years compared to 10.75 years for individuals who were
      not beekeepers. CONCLUSIONS: The high degree of exposure of vespid-venom-allergic
      outdoor workers and bee-venom-allergic beekeepers and subjects living close to
      bee-houses underlines the high benefit of venom immunotherapy for these patients
      even if they suffered a non-life-threatening grade II reaction. Yet, bee-venom
      allergic individuals with no proximity to bee-houses and with an indoor
      occupation face a very low exposure risk, which justifies epinephrine rescue
      treatment for these patients especially if they have suffered from grade II sting
      reactions.

PMID- 22948337
TI  - Randomized trial of distance-based treatment for young children with discipline
      problems seen in primary health care.
AB  - OBJECTIVE: Many parents of preschool-age children have concerns about how to
      discipline their child but few receive help. We examined the effects of a brief
      treatment along with usual care, compared with receiving usual care alone. 
      Patients. Parents (N = 178) with concerns about their 2- to 5-year olds'
      discipline were recruited when they visited their family physician at 1 of 24
      practices. METHODS: After completing mailed baseline measures, parents were
      randomly assigned to receive usual care or the Parenting Matters intervention
      along with usual care. Parenting Matters combined a self-help booklet with two
      calls from a telephone coach during a 6-week treatment period. Follow-up
      assessments were completed at 7 weeks post-randomization, and 3 and 6 months
      later. RESULTS: Behaviour problems (Eyberg Child Behaviour Inventory) decreased
      significantly more in the Parenting Matters condition compared with Usual Care
      alone, based on a significant time by treatment group effect in intent-to-treat,
      growth curve analyses (P = 0.033). The Parenting Matters group also demonstrated
      greater and more rapid improvement than in usual care alone in terms of overall
      psychopathology (Child Behaviour Checklist, P = 0.02), but there were no group
      differences in parenting. The overall magnitude of group differences was small (d
      = 0.15 or less). CONCLUSION: A brief early intervention combining a self-help
      booklet and telephone coaching is an effective way to treat mild behaviour
      problems among young children. This minimal-contact approach addresses the need
      for interventions in primary health care settings and may be a useful component
      in step-care models of mental health.

PMID- 22948339
TI  - Does allergen-specific immunotherapy induce contact allergy to aluminium?
AB  - Persistent, itching nodules have been reported to appear at the injection site
      after allergen-specific immuno-therapy with aluminium-precipitated antigen
      extract, occasionally in conjunction with contact allergy to aluminium. This
      study aimed to quantify the development of contact allergy to aluminium during
      allergen-specific immunotherapy. A randomized, controlled, single-blind
      multicentre study of children and adults entering allergen-specific immunotherapy
      was performed using questionnaires and patch-testing. A total of 205 individuals
      completed the study. In the 3 study groups all subjects tested negative to
      aluminium before allergen-specific immunotherapy and 4 tested positive after
      therapy. In the control group 4 participants tested positive to aluminium. Six
      out of 8 who tested positive also had atopic dermatitis. Positive test results
      were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was
      not shown to be a risk factor for contact allergy to aluminium. Among those who
      did develop aluminium allergy, children and those with atopic dermatitis were
      more highly represented.

PMID- 22948340
TI  - Simultaneous MR-compatible emission and transmission imaging for PET using time
      of-flight information.
AB  - Quantitative positron emission tomography (PET) imaging relies on accurate
      attenuation correction. Predicting attenuation values from magnetic resonance
      (MR) images is difficult because MR signals are related to proton density and
      relaxation properties of tissues. Here, we propose a method to derive the
      attenuation map from a transmission scan. An annulus transmission source is
      positioned inside the field-of-view of the PET scanner. First a blank scan is
      acquired. The patient is injected with FDG and placed inside the scanner. 511-keV
      photons coming from the patient and the transmission source are acquired
      simultaneously. Time-of-flight information is used to extract the coincident
      photons originating from the annulus. The blank and transmission data are
      compared in an iterative reconstruction method to derive the attenuation map.
      Simulations with a digital phantom were performed to validate the method. The
      reconstructed attenuation coefficients differ less than 5% in volumes of interest
      inside the lungs, bone, and soft tissue. When applying attenuation correction in
      the reconstruction of the emission data a standardized uptake value error smaller
      than 9% was obtained for all tissues. In conclusion, our method can reconstruct
      the attenuation map and the emission data from a simultaneous scan without prior
      knowledge about the anatomy or the attenuation coefficients of the tissues.

PMID- 22948342
TI  - Patterns of reassurance seeking and reassurance-related behaviours in OCD and
      anxiety disorders.
AB  - BACKGROUND: Reassurance seeking is particularly prominent in obsessive-compulsive
      disorder (OCD) and may be important in OCD maintenance. AIMS: This study used a
      new self-report questionnaire to measure the range of manifestations of
      reassurance-seeking behaviours, describing their sources from which they seek,
      frequency, process (how they seek), and consequences (as opposed to triggers and
      motivations). This study also attempts to identify the degree to which
      reassurance is specific to OCD as opposed to panic disorder. METHOD: Reassurance
      Seeking Questionnaire (ReSQ) was administered to 153 individuals with OCD, 50
      individuals with panic disorder with/without agoraphobia, and 52 healthy
      controls. The reliability and validity of the measure was evaluated and found to
      be satisfactory. RESULTS: Reassurance seeking was found to be more frequent in
      both anxiety disorders relative to healthy controls. Individuals diagnosed with
      OCD were found to seek reassurance more intensely and carefully, and were more
      likely to employ "self-reassurance" than the other two groups. CONCLUSIONS:
      Further investigation of reassurance will enable better understanding of its role
      in the maintenance of anxiety disorders in general and OCD in particular.

PMID- 22948343
TI  - [Antiretroviral treatment of HIV-1 infection].
AB  - Antiretroviral treatment of HIV-1 infection requires a combination of compounds
      from different drug classes. It aims at life-long virus suppression, resulting in
      prevention of disease progression and improvement of life expectancy as well as
      quality of life. Efficacy, resistance, side effects, drug interactions, and
      patient preferences have to be considered along with factors improving long-term
      high-level adherence. Treatment indication is primarily based on clinical
      symptoms and CD4(+) T-cell count. In view of the perspective of treatment over
      decades, the complexity of therapeutic considerations increases and requires a
      high level of continuing medical education.

PMID- 22948344
TI  - [Advances in management of HIV infections].

PMID- 22948345
TI  - [Spontaneous hematoma and hip pain in a 65-year old patient].
AB  - The case of a 65-year-old woman with acquired hemophilia is reported. Acquired
      hemophilia is characterized by the development of inhibitors directed against
      coagulation factors. Impairment of plasmatic hemostasis leads to a severe
      bleeding tendency in individuals without a preexisting coagulation defect with
      considerable mortality. Pathophysiology, diagnostic work-up, and treatment are
      summarized and discussed.

PMID- 22948346
TI  - [Medication in the elderly : cognitive impairment by drugs].
AB  - Cognitive impairment is a growing problem in aging societies, and dementia is
      turning into an epidemic. Modifiable conditions are of major interest, as a
      causal treatment of dementia is still unknown. Drugs represent a major reversible
      contributor to cognitive deficits and delirium which is seen in 12-50% of elderly
      in-hospital patients. A third of patients with delirium is being attributed to
      drugs, and age-related multimorbidity and subsequent polypharmacy are dominant
      risk factors. The anticholinergic mechanism is not sufficient to explain delirant
      drug side effects. Most prevalent in the induction of delirium are psychotropic
      drugs, in particular benzodiazepines, opiates, tricyclic antidepressants, and
      typical neuroleptics. In addition, "peripheral" drugs such as oxybutynin or
      fluorquinolones are involved. Rationalization of drug therapy is the clue for the
      prevention of cognitive impairment and delirium; most causative drugs are
      contained in negative lists (e.g., Beers list) and should be replaced by
      positively labelled drugs (e.g., by virtue of the FORTA classification). On top
      of the treatment of other modifiable causes for delirium (such as dehydration,
      infections, and fever), the avoidance or at least optimization of psychotropic
      drug prescriptions are key elements of the prevention of cognitive impairment in
      the elderly.

PMID- 22948347
TI  - [Unclear tetraparesis under immunosupression].
AB  - We report a case of a 69-year-old man who developed tetraparesis and muscular
      pain under the therapy of prednisolone for several months. Diagnosis was sepsis
      due to pyomyositis with multiple septic pulmonary staphylococcus aureus
      abscesses. Antibiotic therapy with piperacillin and tazobactam resulted in a
      decrease of the inflammatory factors and improvement of the tetraparesis.
      Pyomyositis, common in tropical areas, is a suppurative infection of striated
      muscle. Immunodeficiency has been implicated in the development of pyomyositis in
      temperate climates.

PMID- 22948348
TI  - Segmentation of computer tomography image using local robust statistics and
      region-scalable fitting.
AB  - Intensity inhomogeneity may cause considerable difficulties in segmentation of CT
      image. In order to overcome the difficulties caused by intensity inhomogeneity,
      the region-scalable fitting (RSF) model was put forward. RSF model draws upon
      intensity information in local regions with a controllable scale. But only using
      intensity information may lead to slow convergence rate and poor denoise ability.
      Combining the method of robust statistics, RSF model is improved in this paper.
      In the improved model, the intensity in RSF model is replaced with local robust
      statistics which is the weighted combination of inter-quartile range, mean
      absolute deviation and intensity median in local region. Inter-quartile range and
      mean absolute deviation in local region are introduced to sharpen object
      boundaries, and intensity median in local region is introduced to reduce image
      noise. The contrast experiments between RSF model and the improved model are
      provided, which demonstrate the fast convergence rate and robustness to noise of
      the improved model.

PMID- 22948349
TI  - Feasibility study of a plasma display-like radiation detector for X-ray imaging.
AB  - In this study we have investigated a 2-dimensional gas type detector based on
      plasma display technology as a candidate for the flat-panel radiation detector.
      By using the Garfield code, the dependence of X-ray absorption and multiplication
      on gas composition, cell gap and electric field were examined. Considering the
      simulation results, three prototype detectors were designed and fabricated. The
      performance of these detectors was evaluated by measuring the collected charge
      density, dark current density and sensitivity. The collected charge had the
      highest value at a condition when Xe 100% and 2.8 mm gap was 108.8 nC/cm2 at 1000
      V. The dark current of the same detector was varied from 0.0095 to 0.10 nA/cm2
      and about a fourth of the dark current density of a-Se based detector was at the
      bias range of 100-1000 V. The sensitivity of Xe 100% and 2.8 mm detector was 0.20
      nC/mR.cm2 at 0.36 V/um. It is about a tenth lower than that of a-Se based
      detector at 10 V/um.

PMID- 22948350
TI  - TV-based image reconstruction of multiple objects in a fixed source-detector
      geometry.
AB  - In this paper, we study how to reconstruct multiple objects tomographically from
      their overlapped x-ray projections. We propose a new rotation-translation
      scanning mode for a fixed source-detector geometry, in which the objects are
      individually translated periodically while they are rotated during the data
      acquisition. The reconstruction scheme performs SART reconstruction and TV
      minimization alternatingly. The scanning parameters are evaluated in a series of
      numerical experiments. Promising results are obtained in the cases of two and
      four objects respectively. The major advantage of our approach is that the
      scanning time can be reduced by about 46% (for two objects) and 67% (for four
      objects) respectively, improving the imaging facility throughput significantly.

PMID- 22948351
TI  - Embedded soft-tissue image mechanism of a small animal shell with synchrotron
      based micro-CT.
AB  - Synchrotron-based micro-CT was utilized to image the embedded biological soft
      tissue of a small animal shell. Micro-CT images of the biological soft-tissue
      were acquired using 20, 25, and 27 keV synchrotron X-rays with contrast agents,
      such as water, physiological saline and iodine. Visualized the complex features
      of the animal at the above energies with water, physiological saline and iodine.
      The choice of the optimum energy was chosen based on the contrast mechanisms to
      know more about soft-matter and the associated internal complex biological
      features of the small animal shell. This way, the images at 27 keV (optimum
      energy) was reasonably acceptable for better visualization of the interior micro
      architecture, such as soft-anatomy, physiology and internal organs of the animal
      with better visibility. The introduction of water, physiological, or iodine as
      contrast agents is shown to enhance minute image features in synchrotron-based
      tomographic imaging.

PMID- 22948352
TI  - A correction method for dual energy liquid CT image reconstruction with metallic
      containers.
AB  - With its capability of material discrimination, dual energy computed tomography
      (DECT) is widely used in security inspection for the purpose of detecting
      contraband. DECT provides effective atomic number image and electron density
      image in addition to traditional attenuation images. In dual energy liquid
      inspection system, the presence of metallic containers will cause partial volume
      effect (PVE) that leads to severe deviation in effective atomic number image.
      Usually, the deviation is too large for a reliable material discrimination and
      may cause false results. In this paper, a projection splitting method is proposed
      to combat the PVE. This method is based on the assumption that a prior projection
      of the empty container is available and photoelectric and Compton coefficient
      integrals can be calculated via dual energy decomposition. Each integral is split
      into two parts by subtracting the integral of the empty container from the total
      integral. The subtraction removes the integral part contributed by the container,
      thus discarding the error source created by PVE that appears on the boundary of
      the sinogram. Images are reconstructed in which only the interior liquid area
      remains. Experiments are performed in a real liquid inspection system to
      demonstrate the effectiveness of this method. Accuracy of the reconstructed
      effective atomic number is greatly improved with this method, which helps a lot
      in determining the type of the object.

PMID- 22948353
TI  - Yields of positron and positron emitting nuclei for proton and carbon ion
      radiation therapy: a simulation study with GEANT4.
AB  - A Monte Carlo application is developed to investigate the yields of positron
      emitting nuclei (PEN) used for proton and carbon ion range verification
      techniques using the GEANT4 Toolkit. A base physics list was constructed and used
      to simulate incident proton and carbon ions onto a PMMA or water phantom using
      pencil like beams. In each simulation the total yields of PEN are counted and
      both the PEN and their associated positron depth-distributions were recorded and
      compared to the incident radiation's Bragg Peak. Alterations to the physics lists
      are then performed to investigate the PEN yields dependence on the choice of
      physics list. In our study, we conclude that the yields of PEN can be estimated
      using the physics list presented here for range verification of incident proton
      and carbon ions.

PMID- 22948354
TI  - Optimization of a three slit collimation system for a SAXS camera with a
      divergent beam.
AB  - Using the three slit collimation system with a divergent beam simplifies the
      design of a small angle X-ray scattering (SAXS) cameras and improves both flux
      and stability. To achieve the required low angle and a high spatial resolution,
      the collimation system must be optimized in the design and operation phases.
      Simulation of a slit divergent camera yields optimal distance between the beam
      defining slits and optimal distance between sample and detector at which the
      maximum SAXS resolution is achieved with a minimal parasitic scattering for any
      length of the SAXS camera. The narrower the beam defining slits and the longer
      the total camera length, the smaller the minimum resolvable angle and the higher
      the attainable resolution.

PMID- 22948355
TI  - Segmentation of 3D microPET images of the rat brain via the hybrid gaussian
      mixture method with kernel density estimation.
AB  - Segmentation of positron emission tomography (PET) is typically achieved using
      the K-Means method or other approaches. In preclinical and clinical applications,
      the K-Means method needs a prior estimation of parameters such as the number of
      clusters and appropriate initialized values. This work segments microPET images
      using a hybrid method combining the Gaussian mixture model (GMM) with kernel
      density estimation. Segmentation is crucial to registration of disordered 2-deoxy
      2-fluoro-D-glucose (FDG) accumulation locations with functional diagnosis and to
      estimate standardized uptake values (SUVs) of region of interests (ROIs) in PET
      images. Therefore, simulation studies are conducted to apply spherical targets to
      evaluate segmentation accuracy based on Tanimoto's definition of similarity. The
      proposed method generates a higher degree of similarity than the K-Means method.
      The PET images of a rat brain are used to compare the segmented shape and area of
      the cerebral cortex by the K-Means method and the proposed method by volume
      rendering. The proposed method provides clearer and more detailed activity
      structures of an FDG accumulation location in the cerebral cortex than those by
      the K-Means method.

PMID- 22948356
TI  - Investigation of BPF algorithm in cone-beam CT with 2D general trajectories.
AB  - A mathematical derivation was conducted to illustrate that exact 3D image
      reconstruction could be achieved for z-homogeneous phantoms from data acquired
      with 2D general trajectories using the back projection filtration (BPF)
      algorithm. The conclusion was verified by computer simulation and experimental
      result with a circular scanning trajectory. Furthermore, the effect of the non
      uniform degree along z-axis of the phantoms on the accuracy of the 3D
      reconstruction by BPF algorithm was investigated by numerical simulation with a
      gradual-phantom and a disk-phantom. The preliminary result showed that the
      performance of BPF algorithm improved with the z-axis homogeneity of the scanned
      object.

PMID- 22948357
TI  - Mechanism of mitochondrial membrane permeabilization during apoptosis under
      photofrin-mediated photodynamic therapy.
AB  - Photofrin-mediated photodynamic therapy (PF-PDT) can induce cell apoptosis via
      the mitochondria/caspase-3 pathway. Here, we further investigate the mechanism
      involved in the mitochondrial apoptotic process induced by PF-PDT. A high-level
      intracellular reactive oxygen species (ROS) generation in mitochondria,
      mitochondrial swelling, and dissipation of mitochondrial transmembrane potential
      were observed immediately after irradiation, indicating that mitochondria were
      the major ROS generation sites and also the first oxidative damage sites after PF
      PDT treatment. For mitochondrial permeability detection, the decrease of calcein
      fluorescence emission intensity and release of cytochrome c were observed
      immediately after PF-PDT treatment, indicating the occurrence of mitochondrial
      inner membrane permeabilization (MIMP) and the mitochondrial outer membrane
      permeabilization (MOMP). However, cytochrome c release was not prevented by
      cyclosporine (CsA), a specific inhibitor of mitochondrial permeability transition
      (MPT). Taken together, these results demonstrated that PF-PDT caused simultaneous
      onset of MIMP and MOMP immediately after the treatment, and MOMP was independent
      of the MPT. Besides, inducible mitochondrial ROS generation played key roles in
      PF-PDT-induced cell apoptosis. This study will be benefit for understanding the
      mechanism involved in the initial mitochondrial oxidative damage by PF-PDT.

PMID- 22948358
TI  - The usefulness of magnetic resonance imaging for sequestered lumbar disc
      herniation treated with endoscopic surgery.
AB  - Forty two patients with sequestered lumbar intervertebral disc herniation were
      treated by endoscopic surgery with the mobile Endospine system. The herniations
      and migration were confirmed on magnetic resonance imaging (MRI). The interlamina
      fenestration and pars interarticularis fenestration approaches were used for
      intracanal herniations and far lateral lumbar disc herniations (FLLDH) according
      to the degree of migration as observed on MRI. Sequestered herniations were
      exposed and removed completely with the mobile endoscopic system for all patients
      without neurologic complications or dural tears. Intraoperative findings were
      compared with preoperative MRI results. Of 24 caudal intracanal herniations, 15
      had sequestered nuclei located ventrally beneath the dural theca and the
      transverse nerve root; 5 were between the transverse nerve root and dural theca
      (axillary); 4 were dorsally located on the nerve root and dural theca. However,
      preoperative MRI did not clearly display the sequestered nuclei between the
      transverse nerve root and dural theca (axillary), or the dorsally migrated disc
      on the nerve root and dural theca. Of 6 cranial intracanal herniations, 5 had
      free fragments located beneath the dural theca, and 1 dorsal to the dural sac. Of
      the 2 dorsal herniations, the migrated nucleus adhered to the dural sac was not
      found on preoperative MRI; in the other case, dorsal migration of nucleus,
      annulus and endplate around the dural sac was also not observed on preoperative
      MRI. Among the 10 FLLDH, preoperative MRI showed cranial migration and foraminal
      obstruction in all patients, with sequestered disc material at the ventral and
      medial sides of the exiting nerve root, displacing the exiting nerve root and
      ganglion cranially and dorsally. During the 12 to 48 month postoperative follow
      up period, 26 patients had excellent clinical results and 15 patients had good
      results (Macnab scale). In conclusion, MRI is important for evaluating
      sequestered lumbar disc herniation, although it has its limitations. Sequestered
      herniations can be exposed and removed completely with the mobile endoscopic
      system.

PMID- 22948360
TI  - Synergistic increase in the sensitivity of osteosarcoma cells to
      thermochemotherapy with combination of paclitaxel and etoposide.
AB  - Osteosarcoma is a malignant bone tumor which is found most commonly in
      adolescents and young adults. Local perfusion thermochemotherapy has long been
      proposed as an alternative strategy for the treatment of osteosarcoma. As a
      standard anticancer drug, paclitaxel plays a significant role in the treatment of
      a number of tumors; however, little is known concerning its ability to promote
      thermochemotherapy. The aim of this study was to evaluate the cytotoxic effects
      of a combination of paclitaxel and etoposide on an osteosarcoma cell line in the
      presence of hyperthermia and to investigate the related mechanism. Our study
      indicated that 1 h after the application of a combination of 10 ug/ml paclitaxel
      and 5 ug/ml etoposide to OS732 cells at 43C, the survival rate of the cells was
      14.52% which was significantly lower than when either 10 ug/ml paclitaxel
      (45.83%) or 5 ug/ml etoposide (43.31%) was applied alone (P<0.01). Moreover,
      changes in cellular morphology and apoptotic rates indicated that the apoptosis
      inducing effect of the combination was much stronger than that of either drug
      applied individually. Fas expression levels in the OS732 cells were increased by
      the combination of paclitaxel and etoposide in the presence of hyperthermia.
      Therefore, paclitaxel enhances the thermochemotherapy of the osteosarcoma cell
      line and this is primarily accomplished by the upregulation of Fas expression and
      the induction of apoptosis.

PMID- 22948361
TI  - New insights into the mechanism of electron transfer within flavohemoglobins:
      tunnelling pathways, packing density, thermodynamic and kinetic analyses.
AB  - Flavohemoglobins (FlavoHb) are metalloenzymes catalyzing the reaction of nitric
      oxide dioxygenation. The iron cation of the heme group needs to be preliminarily
      reduced to the ferrous state to be catalytically competent. This reduction is
      triggered by a flavin adenine dinucleotide (FAD) prosthetic group which is
      localized in a distinct domain of the protein. In this paper we obtain new
      insights into the internal long range electron transfer (over ca. 12 A) using a
      combination of experimental and computational approaches. Employing a time
      resolved pulse radiolysis technique we report the first direct measurement of the
      FADH-> HemeFe(III) electron transfer rate. A rate constant of (6.8 +/- 0.5) *
      10(3) s(-1) is found. A large panel of computational approaches are used to
      provide the first estimation of the thermodynamic characteristics of the internal
      electron transfer step within flavoHb: both the driving force and the
      reorganization energy are estimated as a function of the protonated state of the
      flavin semi-quinone. We also report an analysis of the electron pathways involved
      in the tunnelling of the electron through the aqueous interface between the
      globin and the flavin domains.

PMID- 22948362
TI  - Critical care nursing quarterly.

PMID- 22948363
TI  - A new era in the ICU: the case for telemedicine.
AB  - Management of the patient in the intensive care unit requires constant vigilance
      and monitoring. The nursing staff, and physicians must be readily available to
      alter therapy in response to adverse physiological changes and life-threatening
      events. In the face of limited staffing and overwhelming workloads, telemedicine
      has become a mainstay in ensuring safety for the critically ill patient. Nurses
      must respond to the challenge to utilize every aspect of this technology, and to
      become an active partner in improving the utilization of this tool for accessing
      physician interface and ensuring support when decision-making and immediate
      actions are required for optimum clinical outcomes.

PMID- 22948364
TI  - Use of change management theories in gaining acceptance of telemedicine
      technology.
AB  - The success of telemedicine applications within health care begins with the
      process of implementing planned change. The attitudes of staff and their
      willingness to embrace new technology can be positively influenced in order to
      gain acceptance of new ways to perform tasks. Telemedicine applications have been
      designed to improve operational efficiency and obtain improved outcomes, but
      system designers and procurers are dependent upon the organization's leadership
      to effect attitudinal and behavioral changes that are essential for acceptance
      and usage of new technology.

PMID- 22948365
TI  - Increasing communication in the intensive care unit: is blogging the answer?
AB  - Effective communication is a key factor to success in intensive care nursing. At
      Allegheny General Hospital in Pittsburgh, Pennsylvania, a cardiac intensive care
      unit (ICU) incorporated blogging as one of its primary means of communication. In
      the health care clinical environment, blogging can help to promote 2-way
      communication among nursing staff and leadership. Blogging can serve as a
      valuable method of relaying important updates, changes in practice, and
      educational resources. Incorporating a blog into the ICU environment involves a
      cultural shift and some potential barriers. Lack of a technological understanding
      of social media, outdated software systems, and limited hospital policies may
      pose issues when incorporating a blog into the health care setting. The benefits
      though are impressive. Blogging is a form of rapid, real-time communication for
      which any person may post or comment on an important thought or message. Blogging
      can help to increase compliance with quality measures, update staff on need to
      know information such as changes in policies and procedures, and provide up-to
      date educational resources at any time, from anywhere.

PMID- 22948366
TI  - Integration of evidence-based knowledge management in microsystems: a tele-ICU
      experience.
AB  - The Institute of Medicine's proposed 6 aims to improve health care are timely,
      safe, effective, efficient, equitable, and patient-centered care. Unfortunately,
      it also asserts that improvements in these 6 dimensions cannot be achieved within
      the existing framework of care systems. These systems are based on unrealistic
      expectations on human cognition and vigilance, and demonstrate a lack of
      dependence on computerized systems to support care processes and put information
      at the point of use. Knowledge-based care and evidence-based clinical decision
      making need to replace the unscientific care that is being delivered in health
      care. Building care practices on evidence within an information technology
      platform is needed to support sound clinical decision-making and to influence
      organizational adoption of evidence-based practice in health care. Despite
      medical advances and evidence-based recommendations for treatment of severe
      sepsis, it remains a significant cause of mortality and morbidity in the world.
      It is a complex disease state that has proven difficult to define, diagnose, and
      treat. Supporting bedside teams with real-time knowledge and expertise to target
      early identification of severe sepsis and compliance to Surviving Sepsis
      Campaign, evidence-based practice bundles are important to improving outcomes.
      Using a centralized, remote team of expert nurses and an open-source software
      application to advance clinical decision-making and execution of the severe
      sepsis bundle will be examined.

PMID- 22948367
TI  - Video consultation for trauma and emergency surgical patients.
AB  - The saying goes that a picture is worth a thousand words, but what then is the
      value of video? For the care of trauma and emergency surgical patients, the use
      of video consultation between medical providers may be worth its weight in gold.
      Telemedicine has become an important tool in reducing the disparity among the
      haves and the have not's, in this case facilities with a trauma service and those
      without. This article presents the use of live video for trauma consultations
      between the only level 1 trauma center in Southern Arizona and several smaller
      rural hospitals. We also expand on what we believe the future and direction of
      telesurgery in the fields of critical care and trauma surgery.

PMID- 22948368
TI  - Building a telehealth network through collaboration: the story of the nebraska
      statewide telehealth network.
AB  - With the recent governmental focus on increasing broadband capabilities
      throughout the nation, with rapid advances in technology, and with other
      regulatory and reimbursement barriers falling, a great number of sites across the
      United States are in the process of either initiating or expanding their
      Telehealth capabilities. The Nebraska Statewide Telehealth Network, one of the
      most comprehensive networks in the nation, is no exception. Built through a
      collaborative effort of hospitals, health departments, the Nebraska Hospital
      Association, and other organizations, the Network's members include nearly every
      hospital and health department in the State. The Nebraska Statewide Telehealth
      Network has been awarded more than $1.4 million in grant funding since 2008 and,
      last year, provided 3633 clinical consultations to rural residents across the
      State.Among its many benefits, Telehealth increases access to specialty care for
      patients in rural areas; decreases travel time and saves money for patients and
      caretakers alike; provides the potential for earlier disease intervention;
      enhances clinical support between specialists and primary care providers; and
      serves as a medium for easy access to professional education, training, and
      collaboration. And, now, this technology is becoming increasingly mobile,
      allowing practitioners the opportunity to connect anywhere. In a rural state
      dominated by Health Care Professional Shortage Areas and Medically Underserved
      Areas, Telehealth has the opportunity to help patients receive care at home.

PMID- 22948369
TI  - Professional accountability in the tele-ICU: the CCRN-E.
AB  - The American Association of Critical-Care Nurses (AACN) is the world's largest
      specialty nursing organization. The AACN Certification Corporation provides
      credentialing to validate nursing practice in acute and critical care. The advent
      of tele-ICU nursing added a challenge to the application of certification in a
      new specialty area. Nurses working in a tele-ICU have many years of experience in
      hands-on acute or critical care nursing at the bedside. In their role as tele-ICU
      nurses, these skills are applied to the assessment, evaluation, and decision
      support of care for critically ill patients in various acute and critical care
      units from remote locations connected directly to the ICU through high-speed
      audio and video technology. This article outlines the journey of the advent of
      the CCRN-E (registered nurse in critical care) credential and its place in the
      new specialty of tele-ICU nursing practice.

PMID- 22948370
TI  - How to develop a tele-ICU model?
AB  - The concept of the tele-ICU (intensive care unit) is about 30 years old and more
      hospitals are utilizing it to cover multiple hospitals in their system or for
      hospitals that lack on-site critical care coverage such as in the rural setting.
      Doing a needs analysis, picking the appropriate committee to oversee development
      of the correct model, choosing quality metrics to measure, and designing an
      implementation plan that has a timeline is how the process should begin. Research
      including visitation to established programs and connecting with professional
      societies are helpful. Developing both a business and financial plan will
      optimize the value of a tele-ICU program. The innovative ICU nursing director
      will help to integrate a telemedicine program seamlessly with the on-site program
      to insure a successful program that benefits patients, their families, the ICU
      staff, and the hospital.

PMID- 22948371
TI  - Different systems and formats for tele-ICU coverage: designing a tele-ICU system
      to optimize functionality and investment.
AB  - Technology always changes, yet change or evolution within the tele-ICU has been
      slow. In developing a modern telemedicine system to manage acute illness, there
      are several concepts the developer/administrator should consider to include
      "scalability," centralized/decentralized systems, open/closed architecture,
      inclusivity of the medical community, mobile technology, price set, and
      governmental regulation. The intent of this manuscript is to apply these concepts
      to current tele-ICU technology, explain the concepts in some depth, and finally,
      to speculate as to how the future tele-ICU might look.

PMID- 22948372
TI  - The effect of a family support intervention on physician, nurse, and family
      perceptions of care in the surgical, neurological, and medical intensive care
      units.
AB  - Many patients in the intensive care unit (ICU) have predictable medical and
      discharge outcomes, but some trajectories are marked with medical uncertainty.
      Stressed family-surrogates receive multiple medical updates from a variety of
      personnel. These circumstances can lead to confusion, which may result in
      conflicts and dissatisfaction with care. This study examined the effects of
      adding a family support coordinator to the surgical, neurological, and medical
      ICUs on family, physician, and nurse satisfaction with communication and care. A
      quasi-experimental design was conducted in 2 sequential phases (baseline and
      intervention). The data sources were 2 surveys: (1) Family Satisfaction Survey
      and (2) Nurse and Physician Perception and Satisfaction Survey. Family
      Satisfaction Survey data, a combined data set, were collected in the 3 ICUs.
      Nurse and Physician Perception and Satisfaction Survey data were collected from
      the attending physicians and critical care nurses in the medical and neurological
      ICUs. Results show that family ratings of satisfaction with ICU team
      communication and care generally increased as a result of the intervention.
      Overall, physician and nurse perceptions of communication and care did not change
      as a result of the intervention.

PMID- 22948373
TI  - Concept analysis: compassion fatigue and effects upon critical care nurses.
AB  - Walker and Avant's method of concept analysis was used to delve into the initial
      understanding of compassion fatigue, a relatively new concept being explored with
      critical care nurses and other health care professionals. The term was originally
      used in 1992 involving research exploring burnout experienced by critical care
      nurses when a trend emerged where nurses appeared to have lost their "ability to
      nurture." The term has since been used synonymously with secondary traumatic
      stress disorder. Two important goals exist for this article: First, theoretically
      to conduct a concept analysis of compassion fatigue, thereby providing
      information for critical care nurses to understand the concept as a universal
      human experience. Second, from a caring perspective, identifying the effects
      related to critical care nurses provides an opportunity to address physical and
      somatic consequences of compassion fatigue that will ultimately become important
      to nursing practice, education, and research.

PMID- 22948374
TI  - Advance directives in an intensive care unit: experiences and recommendations of
      critical care nurses and physicians.
AB  - AIM OF STUDY: This study explored the experiences of critical care nurses and
      physicians with advance directives (ADs) in an intensive care unit (ICU) to
      identify the benefits and limitations of ADs and recommendations for improvement.
      METHODS, SETTING, AND SUBJECTS: This descriptive study, obtained by ethnographic
      means, was implemented in a 22-bed adult medical-surgical ICU in a large
      community hospital in the Midwestern United States. Subjects included 14 critical
      care nurses, 7 attending, and 3 fellow critical care physicians. Subjects were
      interviewed informally and formally. Patient medical records were reviewed for
      ADs. RESULTS AND CONCLUSIONS: Results supported numerous problems with ADs
      described previously and identified additional problems, including inability of
      ADs to prevent unwanted aggressive treatments outside of health care facilities,
      and patient reluctance to share ADs for fear of physicians "throwing in the
      towel" too early. Although most subjects described ADs as "useless," one helpful
      aspect was using ADs to shift perceptions of responsibility for end-of-life
      decision making and outcomes from the family/providers to the patient by
      reframing "pulling the plug" to "honoring patient wishes." Recommendations are
      described, including evolving the current emphasis of increasing completion of
      ADs to encourage patient-family discussions focused on quality of life to
      increase the likelihood of discussions occurring.

PMID- 22948375
TI  - Ordered arrays of polymeric nanopores by using inverse nanostructured PTFE
      surfaces.
AB  - We present a simple, efficient, and high-throughput methodology for the
      fabrication of ordered nanoporous polymeric surfaces with areas in the range of
      cm(2). The procedure is based on a two-stage replication of a master
      nanostructured pattern. The process starts with the preparation of an ordered
      array of poly(tetrafluoroethylene) (PTFE) free-standing nanopillars by wetting
      self-ordered porous anodic aluminum oxide templates with molten PTFE. The
      nanopillars are 120 nm in diameter and approximately 350 nm long, while the array
      extends over cm(2). The PTFE nanostructuring process induces surface
      hydrocarbonation of the nanopillars, as revealed by confocal Raman
      microscopy/spectroscopy, which enhances the wettability of the originally
      hydrophobic material and facilitates its subsequent use as an inverse pattern.
      Thus, the PTFE nanostructure is then used as a negative master for the
      fabrication of macroscopic hexagonal arrays of nanopores composed of
      biocompatible poly(vinylalcohol). In this particular case, the nanopores are 130
      140 nm in diameter and the interpore distance is around 430 nm. Features of such
      characteristic dimensions are known to be easily recognized by living cells.
      Moreover, the inverse mold is not destroyed in the pore array demolding process
      and can be reused for further pore array fabrication. Therefore, the developed
      method allows the high-throughput production of cm(2)-scale biocompatible
      nanoporous surfaces that could be interesting as two-dimensional scaffolds for
      tissue repair or wound healing. Moreover, our approach can be extrapolated to the
      fabrication of almost any polymer and biopolymer ordered pore array.

PMID- 22948376
TI  - p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and
      larynx squamous cell carcinoma.
AB  - CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell
      cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur
      frequently in cancer. Although p16 (INK4a) may be involved in tumor progression,
      the clinical impact and prognostic implications in head and neck squamous cell
      carcinoma (HNSCC) are controversial. The objective of this study was to evaluate
      the frequency of the immunohistochemical expression of p16 (INK4a) in 40
      oropharynx and 35 larynx from HNSCC patients treated in a single institution and
      followed-up at least for 10 years in order to explore potential associations with
      clinicopathological outcomes and prognostic implications. Forty cases (53.3%)
      were positive for p16 (INK4a) and this expression was more intense in non-smoking
      patients (P = 0.050), whose tumors showed negative vascular embolization (P =
      0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P
      = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was
      possible to predict a probability of lower survival (P = 0.055) as well as tumors
      presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010).
      Furthermore, increased risk of recurrence was observed in tumors presenting
      capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a)
      appears to be a common event in patients with oropharynx and larynx squamous cell
      carcinoma and the negative expression of this protein correlated with poor
      prognosis.

PMID- 22948377
TI  - Whole-body vibration decreases the proliferativeb response of TCD4(+) cells in
      elderly individuals with knee osteoarthritis.
AB  - The aim of this study was to investigate the effect of adding whole-body
      vibration (WBV; frequency = 35 to 40 Hz; amplitude = 4 mm) to squat training on
      the T-cell proliferative response of elderly patients with osteoarthritis (OA) of
      the knee. This study was a randomized controlled trial in which the selected
      variables were assessed before and after 12 weeks of training. Twenty-six
      subjects (72 +/- 5 years of age) were divided into three groups: 1) squat
      training with WBV (WBV, N = 8); 2) squat training without WBV (N = 10), and 3) a
      control group (N = 8). Women who were >=60 years of age and had been diagnosed
      with OA in at least one knee were eligible. The intervention consisted of 12
      uninterrupted weeks of squatting exercise training performed 3 times/week.
      Peripheral blood mononuclear cells were obtained from peripheral blood collected
      before and after training. The proliferation of TCD4+ and TCD8+ cells was
      evaluated by flow cytometry measuring the carboxyfluorescein succinimidyl ester
      fluorescence decay before and after the intervention (?). The proliferative
      response of TCD4+ cells (P = 0.02, effect size = 1.0) showed a significant
      decrease (23%) in the WBV group compared to the control group, while there was no
      difference between groups regarding the proliferative response of TCD8+ cells (P
      = 0.12, effect size = 2.23). The data suggest that the addition of WBV to squat
      exercise training might modulate T-cell-mediated immunity, minimizing or slowing
      disease progression in elderly patients with OA of the knee.

PMID- 22948378
TI  - Genetic and environmental influences on blood pressure and physical activity: a
      study of nuclear families from Muzambinho, Brazil.
AB  - Blood pressure (BP) and physical activity (PA) levels are inversely associated.
      Since genetic factors account for the observed variation in each of these traits,
      it is possible that part of their association may be related to common genetic
      and/or environmental influences. Thus, this study was designed to estimate the
      genetic and environmental correlations of BP and PA phenotypes in nuclear
      families from Muzambinho, Brazil. Families including 236 offspring (6 to 24
      years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP
      was measured, and total PA (TPA) was assessed by an interview (commuting,
      occupational, leisure time, and school time PA). Quantitative genetic modeling
      was used to estimate maximal heritability (h2), and genetic and environmental
      correlations. Heritability was significant for all phenotypes (systolic BP: h2 =
      0.37 +/- 0.10, P < 0.05; diastolic BP: h2 = 0.39 +/- 0.09, P < 0.05; TPA: h2 =
      0.24 +/- 0.09, P < 0.05). Significant genetic (r g) and environmental (r e)
      correlations were detected between systolic and diastolic BP (r g = 0.67 +/- 0.12
      and r e = 0.48 +/- 0.08, P < 0.05). Genetic correlations between BP and TPA were
      not significant, while a tendency to an environmental cross-trait correlation was
      found between diastolic BP and TPA (r e = -0.18 +/- 0.09, P = 0.057). In
      conclusion, BP and PA are under genetic influences. Systolic and diastolic BP
      share common genes and environmental influences. Diastolic BP and TPA are
      probably under similar environmental influences.

PMID- 22948379
TI  - Recombinant vaccines and the development of new vaccine strategies.
AB  - Vaccines were initially developed on an empirical basis, relying mostly on
      attenuation or inactivation of pathogens. Advances in immunology, molecular
      biology, biochemistry, genomics, and proteomics have added new perspectives to
      the vaccinology field. The use of recombinant proteins allows the targeting of
      immune responses focused against few protective antigens. There are a variety of
      expression systems with different advantages, allowing the production of large
      quantities of proteins depending on the required characteristics. Live
      recombinant bacteria or viral vectors effectively stimulate the immune system as
      in natural infections and have intrinsic adjuvant properties. DNA vaccines, which
      consist of non-replicating plasmids, can induce strong long-term cellular immune
      responses. Prime-boost strategies combine different antigen delivery systems to
      broaden the immune response. In general, all of these strategies have shown
      advantages and disadvantages, and their use will depend on the knowledge of the
      mechanisms of infection of the target pathogen and of the immune response
      required for protection. In this review, we discuss some of the major
      breakthroughs that have been achieved using recombinant vaccine technologies, as
      well as new approaches and strategies for vaccine development, including
      potential shortcomings and risks.

PMID- 22948380
TI  - Less cognitive and neurological deficits in schizophrenia patients carrying risk
      variant in ZNF804A.
AB  - BACKGROUND: The rs1344706 single nucleotide polymorphism in the ZNF804A gene is a
      common variant with strong evidence for association with schizophrenia. Recent
      studies show an association of rs1344706 with cognitive functioning, and there is
      some evidence suggesting that the risk allele may increase susceptibility for a
      subtype of schizophrenia with relatively spared cognition. METHODS: We tested the
      effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive
      domains (working memory, processing speed and attention) shown to be severely
      impaired in schizophrenia. Also we investigated the effect of rs1344706 on the
      severity of neurological soft signs, subtle impairments in motor and sensory
      functions highly frequent in schizophrenia patients. Neurological soft signs and
      cognitive deficits are central features of schizophrenia and are tightly linked
      with clinical, social and functional outcome. RESULTS: Our results show an
      association of higher rs1344706 risk allele load with improved performance on
      processing speed and with fewer neurological soft signs. CONCLUSIONS: Together
      with other studies, our findings suggest that ZNF804A is associated with a
      subtype of schizophrenia with better cognitive and neurological functioning.
      Discovery of the specific pathways through which ZNF804A is exerting this effect
      may lead to better prevention, diagnosis and treatment for a specific group of
      schizophrenia patients.

PMID- 22948381
TI  - Replication and meta-analysis of TMEM132D gene variants in panic disorder.
AB  - A recent genome-wide association study in patients with panic disorder (PD)
      identified a risk haplotype consisting of two single-nucleotide polymorphisms
      (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be
      associated with PD in three independent samples. Now we report a subsequent
      confirmation study using five additional PD case-control samples (n = 1670 cases
      and n = 2266 controls) assembled as part of the Panic Disorder International
      Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the
      analysis. In the new independent samples of European ancestry (EA), the
      association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed,
      replicated, with the strongest signal coming from patients with primary PD, that
      is, patients without major psychiatric comorbidities (n = 1038 cases and n = 2411
      controls). This finding was paralleled by the results of the meta-analysis across
      all samples, in which the risk haplotype and rs7309727 reached P-levels of P =
      1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals
      of EA with primary PD. In the Japanese sample no associations with PD could be
      found. The present results support the initial finding that TMEM132D gene
      contributes to genetic susceptibility for PD in individuals of EA. Our results
      also indicate that patient ascertainment and genetic background could be
      important sources of heterogeneity modifying this association signal in different
      populations.

PMID- 22948382
TI  - Early childhood temperament predicts substance use in young adults.
AB  - Behavioral inhibition (BI) is an important early childhood marker of risk for
      later psychiatric problems. The current 20-year prospective, longitudinal study
      focused on individual differences in this early temperament and adolescent brain
      function. As adolescents, 83 participants initially identified in infancy with
      the temperament of BI were assessed using functional imaging to examine striatal
      responses to incentives. Five years later, as young adults, these participants
      provided self-report of their substance use. Our findings show that children's
      early temperament interacts with their striatal sensitivity to incentives in
      adolescence to predict their level of substance use in young adulthood. Those
      young adults who, as children, showed the highest levels of BI reported the
      greatest substance use if, as adolescents, they also exhibited striatal
      hypersensitivity to incentives. These longitudinal data delineate one
      developmental pathway involving early biology and brain mechanisms for substance
      use in young adulthood.

PMID- 22948384
TI  - Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal
      cortex of psychotic patients.
AB  - Increasing evidence suggests that epigenetic dysfunction may account for the
      alteration of gene transcription present in neuropsychiatric disorders such as
      schizophrenia (SZ), bipolar disorder (BP) and autism. Here, we studied the
      expression of the ten-eleven translocation (TET) gene family and activation
      induced deaminase/apolipoprotein B mRNA-editing enzymes (AID/APOBEC) in the
      inferior parietal lobule (IPL) (BA39-40) and the cerebellum of psychotic (PSY)
      patients, depressed (DEP) patients and nonpsychiatric (CTR) subjects obtained
      from the Stanley Foundation Neuropathology Consortium Medical Research Institute.
      These two sets of enzymes have a critical role in the active DNA demethylation
      pathway. The results show that TET1, but not TET2 and TET3, mRNA and protein
      expression was increased (two- to threefold) in the IPL of the PSY patients
      compared with the CTR subjects. TET1 mRNA showed no change in the cerebellum.
      Consistent with the increase of TET1, the level of 5-hydroxymethylcytosine (5hmC)
      was elevated in the IPL of PSY patients but not in the other groups. Moreover,
      higher 5hmC levels were detected at the glutamic acid decarboxylase67 (GAD67)
      promoter only in the PSY group. This increase was inversely related to the
      decrease of GAD67 mRNA expression. Of 11 DNA deaminases measured, APOBEC3A mRNA
      was significantly decreased in the PSY and DEP patients, while APOBEC3C was
      decreased only in PSY patients. The other APOBEC mRNA studied failed to change.
      Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight
      the possible role of altered DNA demethylation mechanisms in the pathophysiology
      of psychosis.

PMID- 22948385
TI  - Motivation for change and barriers to treatment among young cannabis users.
AB  - BACKGROUND/AIMS: Despite cannabis use among adolescents has shown to be related
      to psychosocial and mental health problems, the demand from adolescents for
      professional help is very low, and determinants of motivation for change among
      nonclinical populations remain unknown. The purpose of this study was to assess
      motivation for change among young cannabis users and to identify determinants of
      intention to change and self-change, as well as perceived barriers to seeking
      professional help. METHODS: 261 cannabis users aged 16-21 participated in a
      computerized survey in Spain. RESULTS: Data from this cross-sectional study
      indicated that few users intend to stop taking the drug. Determining factors of
      intention to change were the following: having more drug-related problems,
      paranoid symptomatology and greater concern about the consequences of use. Self
      change was facilitated by lower use of cannabis, and could be hindered by tobacco
      smoking and cannabis dependence. Lack of awareness of the problems and the desire
      to solve one's problems alone constitute the main barriers to seeking
      professional help. CONCLUSIONS: Adolescent cannabis users show low motivation for
      change though experiencing more problems associated with its use emerges as a
      determinant of increased motivation. Several barriers impede this motivation from
      turning into treatment demand.

PMID- 22948383
TI  - Pathogenetic model for Tourette syndrome delineates overlap with related
      neurodevelopmental disorders including Autism.
AB  - Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder
      characterised by motor and vocal tics. Despite decades of research, the aetiology
      of TS has remained elusive. Recent successes in gene discovery backed by rapidly
      advancing genomic technologies have given us new insights into the genetic basis
      of the disorder, but the growing collection of rare and disparate findings have
      added confusion and complexity to the attempts to translate these findings into
      neurobiological mechanisms resulting in symptom genesis. In this review, we
      explore a previously unrecognised genetic link between TS and a competing series
      of trans-synaptic complexes (neurexins (NRXNs), neuroligins (NLGNs), leucine-rich
      repeat transmembrane proteins (LRRTMs), leucine rich repeat neuronals (LRRNs) and
      cerebellin precursor 2 (CBLN2)) that links it with autism spectrum disorder
      through neurodevelopmental pathways. The emergent neuropathogenetic model
      integrates all five genes so far found to be uniquely disrupted in TS into a
      single pathogenetic chain of events described in context with clinical and
      research implications.

PMID- 22948386
TI  - The cost of persistent asthma in Europe: an international population-based study
      in adults.
AB  - BACKGROUND: This study is aimed at providing a real-world evaluation of the
      economic cost of persistent asthma among European adults according to the degree
      of disease control [as defined by the 2006 Global Initiative for Asthma (GINA)
      guidelines]. METHODS: A prevalence-based cost-of-illness study was carried out on
      462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA
      definition), who were identified in general population samples from 11 European
      countries and examined in clinical settings in the European Community Respiratory
      Health Survey II between 1999 and 2002. The cost estimates were computed from the
      societal perspective following the bottom-up approach on the basis of rates,
      wages and prices in 2004 (obtained at the national level from official sources),
      and were then converted to the 2010 values. RESULTS: The mean total cost per
      patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working
      days and days with limited, not work-related activities 62.5%). The expected
      total cost in the population aged 30-54 years of the 11 European countries was
      EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population
      aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509
      (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm
      and having a high BMI significantly increased the individual total cost.
      CONCLUSIONS: Among European adults, the cost of persistent asthma drastically
      increases as disease control decreases. Therefore, substantial cost savings could
      be obtained through the proper management of adult patients in Europe.

PMID- 22948387
TI  - Prospective randomized study of cefepime, panipenem, or meropenem monotherapy for
      patients with hematological disorders and febrile neutropenia.
AB  - The aim of this study was to evaluate the usefulness of carbapenems as initial
      treatment for febrile neutropenia (FN), and in patients unresponsive to this
      initial therapy, to evaluate the efficacy of subsequent treatment with
      aminoglycosides (AGs) or ciprofloxacin (CPFX). FN patients were randomized to
      receive cefepime (CFPM, control), panipenem/betamiprom (PAPM/BP), or meropenem
      (MEPM). Defervescence, an outcome endpoint, was evaluated 3 days later. Patients
      with minimal response were given CPFX or AGs, and their responses were
      reevaluated on day 7. A total of 255 patients were included. The efficacies of
      CFPM, PAPM/BP, and MEPM were comparable. In patients unresponsive to this initial
      therapy, the efficacy of subsequent CPFX and AGs treatments was also similar.
      There was no significant between-arm difference in cumulative efficacy on days 14
      and 30. Adverse reactions were infrequent and mild. In conclusion, PAPM/BP and
      MEPM are as useful as CFPM as initial therapy for FN, and AGs are as efficacious
      as CPFX in patients unresponsive to the initial therapy.

PMID- 22948388
TI  - Control of arthritis pain with anti-nerve-growth factor: risk and benefit.
AB  - Arthritis is characterized by pain and inflammation. Recently, attention has been
      focused on nerve-growth factor (NGF), a neurotrophin that is a key regulator of
      peripheral nociception because it mediates overexpression of proinflammatory
      neuron-derived molecules such as substance P, serotonin, and calcitonin gene
      related peptide. Antibodies have been generated for NGF and its receptor that are
      effective in reducing pain in preclinical pain models, and clinical trials in
      patients with advanced knee and hip osteoarthritis and low-back pain. Results
      show pain reduction is rapid and sustained. Adverse events with anti-NGF included
      transient paraesthesia and edema, rapidly progressive OA, and, in a small number
      of patients treated with both anti-NGF and nonsteroidal anti-inflammatory drugs,
      osteonecrosis. Inhibition of the NGF-stimulated nociceptive pathway seems to be
      effective; however, the adverse effects require further investigation.

PMID- 22948389
TI  - Can long-term hearing preservation be expected in children following
      cholesteatoma surgery? Results from a 14-year-long study of atticotomy-limited
      mastoidectomy with cartilage reconstruction.
AB  - OBJECTIVE: Following cholesteatoma surgery, effective long-term hearing
      preservation in children is difficult and is not typically expected. Hence, long
      term data on hearing outcomes are lacking. The aim of this study was to analyze
      long-term hearing outcomes in children following cholesteatoma surgery. METHODS:
      For this study, 49 ears in 47 children (<=16 years) with acquired cholesteatomas
      following atticotomy-limited mastoidectomy with cartilage reconstruction (inside
      out approach) during 1986-2010 were included. Pre- and post-operative recidivism
      free audiometric results were compared. Hearing success was defined as a post
      operative air conduction (AC) threshold of <=30 dB (serviceable hearing).
      Logistic regression analyses were used to evaluate potential prognostic factors
      that independently contributed to the prediction of hearing success. These
      factors included stapes condition, pre-operative AC threshold, ossicular chain
      integrity, disease severity, age, and gender. RESULTS: The mean duration of
      follow-up was 14.2 years. The post-operative AC (33.55 +/- 15.42 dB) and air-bone
      gap (17.88 +/- 12.94 dB) were significantly improved compared with the pre
      operative AC (42.90 +/- 16.47 dB, p < 0.001) and air-bone gap (30.23 +/- 13.68
      dB, p < 0.001). The probability of hearing success following surgery (40.8%) was
      significantly higher than prior to surgery (24.5%, p = 0.008). Multivariate
      logistic regression analyses revealed a statistically significant correlation
      between hearing success and stapes integrity only (p = 0.005). CONCLUSIONS: This
      study provides important information on effective long-term hearing preservation
      over a mean follow-up of 14 years. In addition, stapes destruction is an
      independent negative prognostic determinant of achieving hearing success. The
      prediction model in this study provides otologists with useful pre-operative
      information to inform patients and parents on expected hearing outcomes and may
      be useful for post-operative observations.

PMID- 22948390
TI  - Do clinical guidelines improve management of sepsis in critically ill elderly
      patients? A before-and-after study of the implementation of a sepsis protocol.
AB  - AIM: Guidelines for the management of sepsis have been published but not
      validated for elderly patients, though a prompt work-up and initiation of
      appropriate therapy are crucial. This study assesses the impact of a sepsis
      protocol on timelines for therapy and mortality in standardized management.
      METHODS: Consecutive patients aged 70 years and older who were diagnosed with
      sepsis and admitted during the observation periods were included in this before
      and-after study at a medical intensive care unit (ICU). Age, sex, and process-of
      care variables including timely administration of antibiotics, obtaining blood
      cultures before the start of antibiotics, documenting central venous pressure,
      evaluation of central venous blood oxygen saturation, fluid resuscitation, and
      patient outcome were recorded. RESULTS: A total of 122 patients were included.
      Sepsis was diagnosed in 22.9 % of patients prior to the introduction of the
      protocol and 57.4 % after introduction. Volume therapy was conducted in 63.9 % of
      the patients (11.5 % preprotocol). Blood culture samples were taken prior to the
      administration of antibiotics in 67.2 % of patients (4.9 % preprotocol), and
      antibiotics were applied early in 72.1 % of patients (32.8 % preprotocol).
      Lactate was set in 77.0 % of patients (11.5 % preprotocol). A central venous
      catheter was inserted in 88.5 % of patients (68.9 % preprotocol), and the target
      central venous pressure was achieved in 64.3 % of patients (47.2 % preprotocol).
      ICU mortality was reduced by 5.2 % and hospital mortality by 6.4 %. CONCLUSIONS:
      The use of standardized order sets for the management of sepsis in elderly
      patients should be strongly recommended for better performance in treatment.
      Compliance with the protocol was associated with reduced length of stay, reduced
      mortality, and improved initial appropriate therapy.

PMID- 22948391
TI  - Long term results of operative treatment of knee osteochondritis dissecans.
AB  - PURPOSE: This retrospective study was designed to evaluate the hypothesis that
      open reduction internal fixation (ORIF) of an unstable osteochondritis dissecans
      (OCD) lesion results in a high percentage of acceptable outcomes at long-term
      follow-up. METHODS: Eight patients who had been treated with ORIF for unstable
      knee OCD lesions were identified. Long-term outcomes were assessed with a
      Subjective Knee Evaluation Form and Knee Examination Form of the International
      Knee Documentation Committee (IKDC 2000) and an OCD specific Hughston rating
      scale. RESULTS: All lesions were healed and stable to arthroscopic probing at 3
      months. At the average follow-up of 14.8 years (range 12-21 years), the mean IKDC
      subjective score was 80.9. In IKDC examination form, six patients reached group A
      (normal) and two patients reached groups B (near normal) and C (abnormal),
      respectively. According to Hughston criteria, three patients were rated
      excellent, three good, one fair, and one poor. CONCLUSIONS: We recommend
      aggressive attempts to preserve articular cartilage in OCD.

PMID- 22948393
TI  - Health effects of low-level radiation: any news?

PMID- 22948394
TI  - First-principles-guided design of ionic liquids for CO2 capture.
AB  - The identification of sorbents that combine selectively and reversibly with CO(2)
      is essential for efficient and economical abatement of ever-increasing CO(2)
      emissions. Room temperature ionic liquids (ILs) are a promising class of
      potential absorbents, especially when modified to chemically combine with CO(2).
      In this perspective we describe the evolution of IL-based CO(2) capture
      chemistries over the last ten years and in particular the important role that
      first principles simulations have played in helping guide those developments.
      Current anion-functionalized ILs achieve high CO(2) capture efficiencies
      tailorable to a wide range of separation conditions and avoid the viscosity
      problems that plagued the earliest amine-functionalized, CO(2)-reactive ILs.
      Further progress is needed to develop ILs able to meet all the requirements of a
      CO(2) separation system, and simulations will play a central role in those
      developments.

PMID- 22948392
TI  - Suppression of HSP70 expression sensitizes NSCLC cell lines to TRAIL-induced
      apoptosis by upregulating DR4 and DR5 and downregulating c-FLIP-L expressions.
AB  - Many cancer cell types are resistant to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis. Here, we examined whether HSP70
      suppression by small interfering RNA (siRNA) sensitized non-small cell lung
      cancer (NSCLC) cells to TRAIL-induced apoptosis and the underlying mechanisms. We
      demonstrated that HSP70 suppression by siRNA sensitized NSCLC cells to TRAIL
      induced apoptosis by upregulating the expressions of death receptor 4 (DR4) and
      death receptor 5 (DR5) through activating NF-kappaB, JNK, and, subsequently, p53,
      consequently significantly amplifying TRAIL-mediated caspase-8 processing and
      activity, cytosolic translocation of cytochrome c, and cell death. Consistently,
      the pro-apoptotic proteins Bad and Bax were upregulated, while the anti-apoptotic
      protein Bcl-2 was downregulated. The luciferase activity of the DR4 promoter was
      blocked by a NF-kappaB pathway inhibitor BAY11-7082, suggesting that NF-kappaB
      activation plays an important role in the transcriptional upregulation of DR4.
      Additionally, HSP70 suppression inhibited the phosphorylation of ERK, AKT, and
      PKC, thereby downregulating c-FLIP-L. A549 xenografts in mice receiving HSP70
      siRNA showed TRAIL-induced cell death and increased DR4/DR5 levels and reduced
      tumor growth. The combination of psiHSP70 gene therapy with TRAIL also
      significantly increased the survival benefits induced by TRAIL therapy alone.
      Interestingly, HSP27 siRNA and TRAIL together could not suppress tumor growth or
      prolong the survival of tumor-bearing mice significantly, although the
      combination could efficiently induce the apoptosis of A549 cells in vitro. Our
      findings suggest that HSP70 suppression or downregulation might be promising to
      overcome TRAIL resistance in cancer.

PMID- 22948395
TI  - The effects of Ang-1, IL-8 and TGF-beta1 on the pathogenesis of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related
      disease for which no disease-altering therapies currently exist. Airway
      remodeling is one of the most important mechanisms in the pathogenesis of COPD
      and is triggered by chronic inflammation mediated by angiopoietin-1 (Ang-1),
      interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1). The aim of
      this study was to investigate the effects of Ang-1, IL-8 and TGF-beta1 on the
      pathogenesis of COPD. Forty-two COPD patients and 10 healthy adults (group A)
      were included in this study. We divided the 42 patients into 4 groups (groups B
      E) according to the severity of the disease. We investigated the levels of Ang-1,
      IL-8 and TGF-beta1 and the levels of pulmonary function (PF) in the stable and
      acute phases of COPD by enzyme-linked immunosorbent assay. We found statistically
      significant differences in the expression levels of Ang-1, IL-8 and TGF-beta1
      between the stable and acute phases in groups B-E. We found statistically
      significant differences in the expression levels of Ang-1 among all groups in the
      stable phase. In addition, there were statistically significant differences in
      the expression levels of TGF-beta1 among all groups. There were statistically
      significant differences in the expression levels of IL-8 between group A and the
      other groups in the stable phase. Furthermore, in groups C-E we found higher
      correlations between Ang-1 and the forced expiratory volume in one second of
      forced vital capacity (FVC) [FEV1(%)] and FEV1/FVC(%) than between TGF-beta1 and
      FEV1(%) and FEV1/FVC(%). We conclude that the blood vessel factor is more closely
      related to the pathogenesis of COPD.

PMID- 22948396
TI  - Forensic evidence against torture. Editorial.

PMID- 22948397
TI  - Dismemberment: cause of death in the Colombian armed conflict.
AB  - The purpose of this paper is to illustrate major findings in the recovery and
      analysis of victims, where dismemberment is the cause of death, but also a manner
      of torture within the context of the armed conflict in Colombia. It is intended
      to provide useful analytical information and to contribute to the correct
      interpretation of forensic analyses in cases of dismemberment and/or in the
      examination of human remains within the context of the Colombian armed conflict.
      The importance of including dismemberment as an opinion in the forensic report by
      correlating the findings on the body, the grave and context of the information
      available, and the accounts on the facts is encouraged. Otherwise these cases
      will be recorded as undetermined cause of death, which does not reflect the
      brutality of the war.

PMID- 22948398
TI  - Supplementary value of functional imaging in forensic medicine.
AB  - AIM: The aim of this study is to evaluate the role of functional imaging for
      forensic purposes. METHODS: We reviewed a few outpatient cases that were sent to
      our department for examination after traumatic events and one case with
      neuropsychic disturbances. RESULTS: Functional imaging showed signs of traumatic
      lesions in the skeletal system, of brain metabolism and of renal failure.
      CONCLUSION: Functional disturbances following traumatic events are in some cases
      more important than morphological abnormalities. Targeted scintigraphic
      examinations could be applied for visualisation of traumatic lesions or
      evaluation of functional disturbances caused by traumatic events. These
      examinations can be used as evidence in the courtroom.

PMID- 22948399
TI  - Neuropsychiatric evidence of waterboarding and other abusive treatments.

PMID- 22948400
TI  - "Not waving, drowning". Asphyxia and torture: the myth of simulated drowning and
      other forms of torture.
AB  - The article will give a brief introduction to what we understand by the term
      Asphyxiation. The main focus will then turn to how Asphyxiation is used as a
      method of torture, (often euphemistically called a "method of interrogation")
      with an overview of wet methods such as immersion in water or the pouring of
      water over the mouth and nose, and dry methods such as the use of
      bags/sacks/masks and how exacerbating factors such as the use of contaminants or
      irritants are used. The recently published International Forensic Expert Group
      Statement on Hooding will be introduced and the notion will be explored that
      during socalled 'enhanced interrogation' asphyxiation or drowning can be
      "simulated."

PMID- 22948401
TI  - Human rights, human wrongs: torture prevention, documentation and prosecution in
      the Philippines.
AB  - This article presents an overview of the challenges faced by human rights
      organizations and survivors of torture in seeking justice despite the
      availability of an anti-torture law in the Philippines. Several legal, political,
      and security-related impediments are cited here to raise the challenge to state
      agencies to undertake steps to break the culture of impunity in the country by
      making the anti-torture law an effective remedy to prevent torture and for the
      victims to obtain redress. This paper draws lessons and recommendations form the
      insights generated by the authors in the course of their participation in the
      IRCT-led FEAT project.

PMID- 22948402
TI  - Statement on access to relevant medical and other health records and relevant
      legal records for forensic medical evaluations of alleged torture and other
      cruel, inhuman or degrading treatment or punishment.

PMID- 22948403
TI  - Wafer scale imprint uniformity evaluated by LSPR spectroscopy: a high volume
      characterization method for nanometer scale structures.
AB  - We exploit the localized surface-plasmon resonance (LSPR) of terahertz gold
      gammadion structures for wafer scale critical dimension metrology of
      nanostructures.  The proposed characterization method, LSPR spectroscopy, is
      based on optical transmission measurements and is benchmarked against numerical
      simulations of imprinted structures characterized by atomic force microscopy.
      There is a fair agreement between the two methods and the simulations enable the
      translation of optical spectra to critical dimensions of the physical structures,
      a concept known from scatterometry. The results demonstrate the potential of LSPR
      spectroscopy as an alternative characterization method to scanning electron
      microscopy, atomic force microscopy and scatterometry.

PMID- 22948404
TI  - Who's Driving? The role and training of the human patient simulation operator.
AB  - Within the airline industry, where much of simulation-based education originated,
      cockpit simulators are operated by current or former pilots whose expertise
      ensures the authenticity of the training experience. As yet, identifying the most
      appropriate person to run a patient simulator has not been translated into
      healthcare. Furthermore, few training resources exist for those who must learn
      the intricacies of the relationship between patient simulators, simulation
      scenarios, and educational objectives. This article reviews literature related to
      the role, educational preparation, and training of the patient simulator operator
      and explores solutions to the uncertainty about the difference between simulator
      operators and technicians. Because simulators are operationally intensive and
      because scarce faculty may be best used to facilitate student learning within the
      laboratory, the tendency has been to use a variety of personnel to manage patient
      simulators. Recommendations for standardizing the role of the operator that are
      consistent with the pedagogical purposes of simulation are offered. Potential
      questions are posed, and methods for future work are discussed.

PMID- 22948405
TI  - Telecare for the elderly--community nurses' experiences in Taiwan.
AB  - Advances in science, technology, and healthcare have contributed to the global
      growth of an aging population. With a concomitant decline in birth rate, the
      increasing need for elder care cannot be met effectively by traditional care
      models as fewer caregivers are available. This study adopted a qualitative
      research method, and 13 nurses who have experiences in telecare were interviewed
      in a regional hospital in northern Taiwan. Data were content analyzed to explore
      nurses' perceptions of telecare services. Five major themes were identified: (1)
      provision of individualized care, (2) increasing job requirements and stress, (3)
      working with a collaborative care model, (4) understanding concerns of the
      elderly, and (5) foreseeing future challenges. The participants identified the
      advantages of telecare services for the elderly and recognized a new opportunity
      for health management in the future population and social changes. The use of
      technology to provide telecare may offer an effective supplement for elder care
      services.

PMID- 22948406
TI  - Meaningful use of data in care coordination by the advanced practice RN: the
      TeleFamilies project.
AB  - Meaningful use of electronic health records to coordinate care requires skillful
      synthesis and integration of subjective and objective data by practitioners to
      provide context for information. This is particularly relevant in the
      coordination of care for children with complex special healthcare needs. The
      purpose of this article is to present a conceptual framework and example of
      meaningful use within an innovative telenursing intervention to coordinate care
      for children with complex special healthcare needs. The TeleFamilies intervention
      engages an advanced practice nurse in a full-time care coordinator role within an
      existing hospital-based medical home for children with complex special healthcare
      needs. Care coordination is facilitated by the synthesis and integration of
      internal and external data using an enhanced electronic health record and
      telehealth encounters via telephone and videoconferencing between the advanced
      practice nurse and the family at home. The advanced practice nurse's ability to
      maintain an updated plan of care that is shared across providers and systems and
      build a relationship over time with the patient and family supports meaningful
      use of these data.

PMID- 22948407
TI  - Vaccination based control of infections in SIRS models with reinfection: special
      reference to pertussis.
AB  - The aim of this paper is to study the impact of introducing a partially
      protective vaccine on the dynamics of infection in SIRS models where primary and
      secondary infections are distinguished. We investigate whether a public health
      strategy based solely on vaccinating a proportion of newborns can lead to an
      effective control of the disease. In addition to carrying out the qualitative
      analysis, the findings are further explained by numerical simulations. The model
      exhibits backward bifurcation for certain values of the parameters. In these
      cases the standard basic reproduction number (obtained by inspection of the
      uninfected state) is not significant. The key threshold is the reinfection level
      which depends on the relative transmissibility (susceptibility) of secondary,
      with respect to primary, infected (susceptible) individuals and the relative loss
      of immunity of vaccinated, with respect to recovered, individuals. If one or all
      of these ratios decrease, then the threshold increases which increases the
      possibility to contain the infection by vaccination. The analysis shows further
      that symptomatic infections can be eliminated by vaccination solely. 

PMID- 22948408
TI  - Extensive chronic Tuberculosis luposa treated incorrectly with long-term course
      of isoniazid monotherapy.

PMID- 22948410
TI  - Silencing HIF-1alpha reduces the adhesion and secretion functions of acute
      leukemia hBMSCs.
AB  - Hypoxia inducible factor-1alpha (HIF-1alpha) is an important transcription
      factor, which plays a critical role in the formation of solid tumor and its
      microenvironment. The objective of the present study was to evaluate the
      expression and function of HIF-1alpha in human leukemia bone marrow stromal cells
      (BMSCs) and to identify the downstream targets of HIF-1alpha. HIF-1alpha
      expression was detected at both the RNA and protein levels using real-time PCR
      and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF)
      and stromal cell-derived factor-1alpha (SDF-1alpha) were detected in stromal
      cells by enzyme-linked immunosorbent assay. HIF-1alpha was blocked by
      constructing the lentiviral RNAi vector system and infecting the BMSCs. The
      Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into
      the same suitable cultured media and conditions. Cell adhesion and secretion
      functions of stromal cells were evaluated after transfection with the lentiviral
      RNAi vector of HIF-1alpha. Increased HIF-1alpha mRNA and protein was detected in
      the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared
      with normal BMSCs. The lentiviral RANi vector for HIF-1alpha was successfully
      constructed and was applied to block the expression of HIF-1alpha. When HIF
      1alpha of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal
      cells were decreased. When HIF-1alpha was blocked, the co-cultured Jurkat cell's
      adhesion and migration functions were also decreased. Taken together, these
      results suggest that HIF-1alpha acts as an important transcription factor and can
      significantly affect the secretion and adhesion functions of leukemia BMSCs.

PMID- 22948409
TI  - Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia
      and reperfusion injury mediated by the JAK2/STAT3 survival pathway.
AB  - The JAK2/STAT3 signal pathway is an important component of survivor activating
      factor enhancement (SAFE) pathway. The objective of the present study was to
      determine whether the JAK2/STAT3 signaling pathway participates in hydrogen
      sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic
      reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6
      groups (N = 14 per group): time-matched perfusion (Sham) group,
      ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490
      group, AG-490 (5 uM) group, and dimethyl sulfoxide (DMSO; <0.2%) group.
      Langendorff-perfused rat hearts, with the exception of the Sham group, were
      subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of
      equilibrium. Heart rate, left ventricular developed pressure (LVDP), left
      ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or
      decrease of left ventricular pressure (+/- dp/dt(max)) were recorded. Infarct
      size was determined using triphenyltetrazolium chloride (TTC) staining.
      Myocardial TUNEL staining was used as the in situ cell death detection method and
      the percentage of TUNEL-positive nuclei to all nuclei counted was used as the
      apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western
      blotting. After reperfusion, compared to the I/R group, H2S significantly
      improved functional recovery and decreased infarct size (23.3 +/- 3.8 vs 41.2 +/-
      4.7%, P < 0.05) and apoptotic index (22.1 +/- 3.6 vs 43.0 +/- 4.8%, P < 0.05).
      However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In
      conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via
      activation of the JAK2/STAT3 signaling pathway.

PMID- 22948411
TI  - Cytogenetic analysis of Lagria villosa (Coleoptera, Tenebrionidae): emphasis on
      the mechanism of association of the Xy(p) sex chromosomes.
AB  - The Xy(p) sex determination mechanism is the system most frequent and ancestral
      to Coleoptera. Moreover, the presence of argyrophilous material associated with
      the sex bivalent is described as being responsible for the maintenance and
      association of these chromosomes. There are no karyotype data available regarding
      the genus Lagria and no consensus in the literature regarding the argyrophilous
      material present in the lumen of sex bivalent. Therefore, the aim of this work
      was to investigate the mechanism of sex chromosome bivalent association in Lagria
      villosa by analyzing the argyrophilous nature of the material present in the
      Xy(p) lumen. It was also intended to characterize L. villosa cytogenetically. The
      analysis of meiotic cells showed 2n = 18 = 16+Xy(p) for males and 2n = 18 = 16+XX
      in females and the meiotic formula was 2n = 8(II)+Xy(p). The C-banding showed
      blocks of pericentromeric heterochromatin in all chromosomes except in the y(p)
      chromosome. In these regions, the use of fluorochromes revealed the presence of
      heterochromatin containing GC rich DNA sequences. The study of synaptonemal
      complex showed a gradual increase in the electron-density of the axial elements
      of the sex chromosomes and their association with strongly electron-dense
      material. The pepsin pretreatment revealed that the material impregnated by
      silver is protein.

PMID- 22948412
TI  - 2-Heptanone increases the firing rate of the basal amygdala: role of anterior
      olfactory epithelial organs.
AB  - Wistar rats subjected to physical stress release a urine alarm pheromone (2
      heptanone) that produces signs of anxiety and despair in receptor rats not
      subjected to physical stress. However, unknown are the effects of 2-heptanone on
      the firing rate of the basal amygdala, a structure that participates in the
      expression of fear, and the participation of anterior olfactory epithelial
      organs, namely the septal organ and vomeronasal organ (SO-VNO). We explored the
      effects of 2-heptanone applied near the nostrils on single-unit extracellular
      recordings from the basal amygdala in a sham-operated group and rats that
      underwent removal of the SO-VNO. The firing rate of basal amygdala neurons in the
      SO-VNO removal group was significantly higher than in the sham-operated group. In
      both groups, recordings were classified according to the responses to 2-heptanone
      (i.e., increased firing rate, decreased firing rate, and no response). SO-VNO
      removal was associated with an increased firing rate in the three types of
      neurons. A similar number of neurons increased their firing rate during and after
      2-heptanone stimulation in both groups, but such an increase in firing rate was
      longer in the group of rats subjected to SO-VNO removal. The results indicate
      that the SO-VNO is not essential for the effect of 2-heptanone on the firing rate
      of basal amygdala neurons. SO-VNO ablation did not block but rather accentuated
      the response of amygdala neurons to 2-heptanone.

PMID- 22948413
TI  - Seeing and liking cigarette advertisements: is there a 'mere exposure' effect?.
AB  - AIMS: We aimed to explain the association between exposure to a cigarette
      advertisement and favorable attitudes towards the advertisement. METHODS: We used
      data from an observational cross-sectional study with a sample of 3,415 German
      schoolchildren aged 10-17 years. Cigarette advertising exposure was assessed with
      an image of a Marlboro ad, asking for contact frequency (number of times seen the
      ad) and brand name. Liking of the ad was measured with two items (alpha = 0.78).
      RESULTS: We found a positive linear association between exposure to the Marlboro
      ad and liking it. This association remained significant (standardized beta =
      0.09; p < 0.001) even after statistical control for smoking status, smoking of
      friends and parents, attitudes towards smoking in general, cigarette advertising
      receptivity (having a favorite cigarette ad), exposure to other advertisings,
      age, sex, socioeconomic status, rebelliousness and sensation seeking, self
      reported school performance, and study region. CONCLUSIONS: The association
      between exposure to an advertisement and liking it was robust and could not be
      fully explained without referring to either unmeasured confounding or implicit
      advertising effects (e.g. mere exposure). Implicit effects have implications for
      prevention strategies as it may be very difficult to counteract unconscious
      advertising effects.

PMID- 22948414
TI  - Nanoscale phase boundaries: a new twist to novel functionalities.
AB  - In functional materials, nanoscale phase boundaries exhibit exotic phenomena that
      are notably absent in their parent phases. Over the past two decades, much of the
      research into complex oxides (such as cuprate superconductors, CMR manganites and
      relaxor ferroelectrics) has demonstrated the key role that nanoscale
      inhomogeneities play in controlling the electronic and/or ionic structure of
      these materials. One of the key characteristics in such systems is the strong
      susceptibility to external perturbations, such as magnetic, electric and
      mechanical fields. A direct consequence of the accommodation of a large number of
      cationic substitutions in complex oxides is the emergence of a number of physical
      phenomena from essentially the same crystal framework. Recently, multiferroic
      behavior, which is characterized by the co-existence and potential coupling of
      multiple ferroic order parameters, has captured considerable worldwide research
      interest. The perovskite, BiFeO(3), exhibits robust ferroelectricity coupled with
      antiferromagnetism at room temperature. A rather unique feature of this material
      system is its ability to "morph" its ground state when an external mechanical
      constraint is imposed on it. A particularly striking example is observed when a
      large (~4 to 5%) compressive strain is imposed on a thin film through the
      epitaxial constraint from the underlying substrate. Under these conditions, the
      ground state rhombohedral phase transforms into a tetragonal-like (or a
      derivative thereof) phase with a rather large unit cell (c/a ratio of ~1.26).
      When the epitaxial constraint is partially relaxed by increasing the film
      thickness, this tetragonal-like phase evolves into a "mixed-phase" state,
      consisting of a nanoscale admixture of the rhombohedral-like phase embedded in
      the tetragonal-like phase. Such a system gives us a new pathway to explore a
      variety of mechanical, magnetic and transport phenomena in constrained
      dimensions. This article reviews our progress to date in this direction and also
      captures some possible areas of future research. We use the electromechanical
      response and the magnetic properties as examples to illustrate that its novel
      functionalities are intrinsically due to the phase boundaries and not the
      constituent phases. The possible origin of the giant piezoelectric response and
      enhanced magnetic moment across the boundaries is proposed based on the
      flexoelectric and flexomagnetic effects.

PMID- 22948415
TI  - Idiopathic sudden sensorineural hearing loss: classic cardiovascular and new
      genetic risk factors.
AB  - BACKGROUND: The main causative process in idiopathic sudden sensorineural hearing
      loss (iSSNHL) has yet to be explained or demonstrated. The clinical picture
      supports vascular involvement, but obvious limitations of inner ear study make
      this difficult to corroborate. OBJECTIVES: To determine the role of thrombophilic
      genetic variants that may affect platelet function and to assess the
      cardiovascular risk profile in a cohort of patients with iSSNHL. PATIENTS AND
      METHODS: 118 Caucasian patients with iSSNHL were recruited from the same
      geographical area and enrolled prospectively in this study. Clinical data were
      obtained for each patient. Polymorphisms of the platelet glycoprotein subunit
      IIIa gene, ITGB3 (PLA1/A2, rs5918), and of the platelet glycoprotein subunit Ia
      gene, ITGA2 (C807T, rs1126643) were analyzed. A control group of 161 age- and
      gender-matched healthy individuals from the same geographical area was recruited
      for genetic comparisons. In order to determine the cardiovascular risk profile of
      each patient and of our cohort, a cross-sectional assessment was performed by
      means of a calibrated Framingham coronary heart disease risk scale. Risk factor
      proportions were compared to those recommended in European guidelines for
      coronary prevention, which are also based on the Framingham function. RESULTS: A
      significantly high prevalence of the 807T allele of platelet glycoprotein subunit
      Ia was found in patients compared to controls. There was a significant
      correlation between the 807TT homozygous genotype and a low probability of
      recovery. The PLA1/A2 polymorphism of platelet glycoprotein subunit IIIa was not
      associated with recovery, with a similar genotype prevalence being found in
      patients and controls. In terms of cardiovascular risk profile, patients did not
      present an excess of baseline coronary risk factors compared to the general
      population in the same geographical area. CONCLUSIONS: Patients with iSSNHL had a
      higher prevalence of the 807T thrombophilic polymorphism of platelet glycoprotein
      Ia/IIa. Patients homozygous for this polymorphism are less likely to recover from
      iSSNHL. Classical cardiovascular risk factors were not related to iSSNHL.

PMID- 22948416
TI  - Effects of atorvastatin on renal function in patients with dyslipidemia and
      chronic kidney disease: rationale and design of the ASsessment of clinical
      Usefulness in CKD patients with Atorvastatin (ASUCA) trial.
AB  - BACKGROUND: Since dyslipidemia has been shown to be an independent risk factor
      for the progression of chronic kidney disease (CKD), low-density lipoprotein
      cholesterol (LDL-C)-lowering therapy can be potentially associated with
      inhibition of CKD progression. The ASsessment of clinical Usefulness in CKD
      patients with Atorvastatin (ASUCA) trial was designed to determine whether
      atorvastatin has protective effects on renal function in patients with
      dyslipidemia and CKD. METHODS: We decided to carry out a prospective multi
      center, open-labeled, randomized trial to compare the reno-protective effects
      between diet therapy alone and atorvastatin plus diet therapy in patients with
      dyslipidemia (LDL-C >= 140 mg/dL if not treated or LDL-C >= 100 mg/dL if treated
      with lipid-lowering drugs in subjects taking dyslipidemia-treating agents other
      than statins) and CKD [estimated glomerular filtration rate (eGFR) < 60
      mL/min/1.73 m(2)]. The primary endpoint is the change in eGFR (mL/min/1.73 m(2))
      as calculated by the modified MDRD equation for Japanese after 2 years of
      treatment. RESULTS: Enrollment began in April 2009 and was completed in March
      2011. A total of 334 patients (213 male and 121 female) were randomly assigned to
      either diet therapy alone or atorvastatin plus diet therapy and included in an
      intent-to-treat population. In the atorvastatin and control groups, the mean ages
      were 63.2 and 63.1 years, mean eGFRs were 55.9 and 54.0 mL/min/1.73 m(2), and
      median urinary albumin/creatinine ratios were 24.9 and 29.1 mg/g, respectively.
      CONCLUSIONS: This study distinguishes itself from similar studies by increasing
      statistical accuracy derived from its significantly larger sample size and
      longitudinal magnitude. The results of this study will help to determine whether
      atorvastatin has reno-protective effects in patients with dyslipidemia and CKD.

PMID- 22948417
TI  - The administration of pitavastatin augments creatinine clearance associated with
      reduction in oxidative stress parameters: acute and early effects.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a serious health problem worldwide.
      Therapies that can halt the progression of CKD are limited, and the
      identification of new strategies for CKD treatment is therefore important.
      Pitavastatin, one of the newest statins introduced to the market, has been shown
      to exhibit some beneficial effects on renal and endothelial function. METHOD: We
      enrolled 12 healthy volunteers for our study. With or without pitavastatin
      administration, creatinine clearance (Ccr), urinary albumin excretion, lipid
      status, and oxidative stress markers were evaluated in acute and early phases
      after administration of the drug. RESULTS: A single pitavastatin administration
      increased Ccr and reduced oxidative stress parameters, such as 8-OHdG levels and
      isoprostane production, within 6 h, without altering lipid status in healthy
      participants. A two-week treatment with pitavastatin lowered total and LDL
      cholesterol and triglycerides but not HDL cholesterol at 7 and 14 days. This
      change in lipid profile is associated with enhanced Ccr and the suppression of
      oxidative stress parameters. Urinary albumin excretion was reduced after either
      acute or chronic administration of pitavastatin, although this effect was not yet
      significant. CONCLUSION: We found that pitavastatin augmented Ccr and reduced
      oxidative stress parameters in healthy subjects. These data suggest that
      pitavastatin affects renal outcomes in both lipid status-dependent and 
      independent manners. These observations suggest that pitavastatin treatment could
      be beneficial for CKD patients.

PMID- 22948419
TI  - Reply to '30th Liverpool course-is this a record?'.

PMID- 22948418
TI  - Recombined sequences between the non-coding control regions of JC and BK viruses
      found in the urine of a renal transplantation patient.
AB  - Kidney cells are the common host for JC virus (JCV) and BK virus (BKV).
      Reactivation of JCV and/or BKV in patients after organ transplantation, such as
      renal transplantation, may cause hemorrhagic cystitis and polyomavirus-associated
      nephropathy. Furthermore, JCV and BKV may be shed in the urine after reactivation
      in the kidney. Rearranged as well as archetypal non-coding control regions
      (NCCRs) of JCV and BKV have been frequently identified in human samples. In this
      study, three JC/BK recombined NCCR sequences were identified in the urine of a
      patient who had undergone renal transplantation. They were designated as JC-BK
      hybrids 1, 2, and 3. The three JC/BK recombinant NCCRs contain up-stream JCV as
      well as down-stream BKV sequences. Deletions of both JCV and BKV sequences were
      found in these recombined NCCRs. Recombination of DNA sequences between JCV and
      BKV may occur during co-infection due to the relatively high homology of the two
      viral genomes.

PMID- 22948420
TI  - [Overcrowding in the hospital emergency department].

PMID- 22948421
TI  - [Analysis of a series pheochromocytoma cases over 15 years].
AB  - BACKGROUND: The pheochromocytoma is a catecholamine secreting tumour derived from
      chromaffin cells of the sympathetic nervous system. Eighty to eighty-five percent
      of these tumours are localized in the adrenal medulla. When pheocromocytomas are
      found outside the adrenal gland they are referred to as extra-adrenal
      pheochromocytomas or paragangliomas. The diagnosis is confirmed by elevation of
      catecholamines and the metanephrines in blood plasma and urine. Localization of
      the tumour should be done following biochemical diagnosis by means of CT scan
      and/or MRI. The treatment of choice is tumour resection by laparoscopic surgery.
      MATERIAL AND METHODS: A review was made of all patient medical histories
      diagnosed with pheochromocytoma confirmed by the pathology reports of
      Pathological anatomy of the Navarre hospital Complex (Anatomia patologica del
      Complejo hospitalario de Navarra A y B) between 1996 to 2010. Descriptive
      analysis was made using the IBM SPSS statistics program. RESULTS: Our series
      consists of 43 patients diagnosed with pheochromocytoma over a span of 15 years.
      The average age on presentation was 47 years. Among the younger patients specific
      genetic syndromes were found. Computerized tomography was the most widely used
      method of localization. Contradictory results were found regarding perioperative
      medical management protocols. All pheocromocytoma tumours in this series were
      benign. CONCLUSIONS: It is advisable to carry out a genetic study on patients
      under twenty. The biochemical indicators with the greatest diagnostic sensitivity
      were the levels of normetanephrine and metanephrine in urine. Surgery was the
      only treatment option.

PMID- 22948423
TI  - [Basic and advanced life support units in Spain: analysis of the current
      situation].
AB  - BACKGROUND: To describe the type and number of emergency care ambulances
      integrated in the Emergency Medical System in the Spanish autonomous communities
      and to calculate their relationship with the assigned population. MATERIAL AND
      METHODS: The official literature of the autonomous communities was reviewed, and
      the type and number of terrestrial care resources integrated in the Emergency
      Medical System and population data for 2011 were extracted. Secondary or
      specialized resources were excluded, and part-time units were computed in
      proportion to operational time. RESULTS: A total of 319 Advanced Life Support
      Units (ALSU) and 1,109.05 Basic Life Support Units (BLSU) were identified, of
      which 31.9 are provided with nursing staff. The national rate of ambulances by
      absolute population was 0.86 ALSU (range 0.32 to 1.44) and 2.35 BLSU (range 0.07
      to 5.30) per 100,000 inhabitants. The state rate by relative population was
      estimated at 0.29 (range 1.06 to 30.22) and 0.08 (range 0.94 to 16.03)
      inhabitants/km2 for ALSU and BLSU respectively, and the national rate by surface
      was 1,586.2 (range 140.8 to 4204.5) and 456.2 km2 (range 44.1 to 14599.6) for
      ALSU and BLSU respectively. CONCLUSIONS: There are significant differences in the
      calculated rates of emergency care resources of autonomous regions over their
      population and area. No relation was found with the geodemographic idiosyncrasies
      of each territory. These differences could be caused by heterogeneity in the
      management of EMS or other factors not considered in this work.

PMID- 22948422
TI  - [Prediction model for in-hospital admission in patients arriving in the emergency
      department].
AB  - BACKGROUND: To develop a prediction model for in-hospital admission to provide an
      almost "real time" determination of hospital beds needed, so as to predict the
      resources required as early as possible. MATERIAL AND METHODS: A prospective
      observational study in the emergency department of a university hospital. We
      included all consecutive patients between 8.00-22.00 hours during one month. We
      analyzed 7 variables taken when the patient arrived at the emergency department:
      age, sex, level of triage, initial disposition, first diagnosis, diagnostic test
      and medication, and we performed a logistic regression. RESULTS: We included
      2,476 visits of which 114 (4.6%) were admitted. A significant direct correlation
      was seen between: age >65 years old (odds ratio[OR]=2.1, confidence interval [CI]
      95%,1.3-3.2; p=0.001); male sex (OR=1.6, IC 95%,1.1-2.4; p=0.020); dyspnea
      (OR=5.2, IC 95%, 2.8-9.7; p<0.0001), abdominal pain (OR=4.7, IC 95%, 2.7-8.3;
      p<0.0001); acute care initial disposition (OR=8.9, IC 95%, 5.4-14.9; p<0.0001),
      diagnostic test (OR=1.1, IC 95%,0.9-1.3; p=0.064) and treatment prescription
      (OR=2.6, IC95%,1.6-4.2; p=<0.0001). The model had a sensitivity of 76% and a
      specificity of 82% (area under curve 0.85 [IC 95% 0.81-0.88; p<0.001]).
      CONCLUSIONS: The in-hospital admission prediction model is a good and useful tool
      for predicting the in-hospital beds needed when patients arrive at the emergency
      department.

PMID- 22948424
TI  - [Determinants of poor mental health in people aged 16 to 64 residing in a large
      city].
AB  - BACKGROUND: Know what factors determine the poor mental health in the city of
      Madrid. MATERIAL AND METHODS: Cross-sectional study Health Survey of the City of
      Madrid (ESCM'05), analyzed 5746, persons aged 16 to 64 years, in the years 2004
      2005. Dependent variable was obtained from the General Health Questionnaire (GHQ
      12), was considered score above 2. Independent variables included
      sociodemographic factors, lifestyle, health and environmental issues. The quality
      of life related to health (HRQOL) was measured with the questionnaire COOP /
      WONCA. RESULTS: The overall prevalence of poor mental health was 19.2%, p <0.05
      for gender, age group 16 to 24 years and lower social classes. The predictors
      most strongly associated with poor mental health in the multiple regression are:
      women OR=1.48 (1.23-1.78), minors OR=3.21 (2.40-4.29), immigrant economic OR=1.33
      (1.06-1.68), smoking or drinking alcohol OR=1.22 (1.02 -1.49) and 1.31 (1.09 
      1.57), chronic disease OR=1.47 (1.21 -1.79), sleeping less 8 hours OR=1.41 (1.17 
      1.68), having fair or poor health status perception OR=1.65 (1.22-2.22), self
      perceived poor quality of life HRQOL OR=1.18 (1.15-1.22), and limited social
      activities OR=1.34 (1.07 -1.69) . CONCLUSIONS: The mental health problems are
      highly prevalent in this city. Being woman, young, economic migrant, worse
      lifestyles, poor quality of life refered or limited social activities are the
      factors that force to explain the association with poor mental health.

PMID- 22948425
TI  - [Back pain and restricted daily physical activity in the Spanish adult
      population].
AB  - BACKGROUND: Low back pain is a widespread health problem that affects a great
      part of the Spanish adult population; it also places a constraint on developing
      activities of daily living. The aim of this paper is to estimate the association
      between daily physical activity and chronic back pain in Spain. MATERIAL AND
      METHODS: This paper analyses data from the European Health Survey in Spain 2009;
      it presents a cross sectional epidemiological study designed to assess the health
      of the Spanish population, in which 22,188 people participated (10,876 men and
      11,312 women over 16 years ), representative of the total Spanish population. The
      variables studied are: back pain indicators obtained from the European Health
      Status Module and the European Health Care Module included in this survey, and
      the daily physical activity pattern obtained from the European Module of Health
      Determinants. RESULTS: The total volume of daily physical activity is similar in
      healthy people and those who have back pain, but a pattern of low or moderate
      intensity in people with chronic back pain in the last twelve months (p <0.01)
      was observed with greater frequency. CONCLUSIONS: People with chronic back pain
      do not show a lower volume of physical activity, but their physical activity
      pattern is often low or moderate. Developing a vigorous pattern of physical
      activity should be considered not only as a strategy to prevent this disease, but
      also as a therapeutic target in these patients.

PMID- 22948426
TI  - [Factors associated with willingness to be vaccinated against pandemic flu A/H1N1
      in the adult population of the Health Department of Elche (Spain)].
AB  - BACKGROUND: To assess, in the general population, the information sources,
      attitudes and willingness to be vaccinated against pandemic influenza A/H1N1 in
      2009. METHODS: We carried out a cross sectional study between 25th November and
      30th December 2009, through face to face interviews with a random sample (826) of
      adults resident in the Health Department of Elche (Spain). RESULTS: Respondents
      reported that television (57%) and the family doctor (47.9%) were their main
      sources of information about vaccinations. Eighty-two point two percent had a
      good opinion of vaccinations, 30.5% perceived A/H1N1 to be more severe than
      seasonal flu, with a higher rate among older and less educated people. Twenty
      five point four percent of respondents were concerned about contracting it,
      especially among the less educated. Forty-two point one percent expressed their
      willingness to be vaccinated against seasonal flu. Eighteen point four percent
      intended to be vaccinated against A/H1N1. The bias towards vaccination increases
      with age and in the case of A/H1N1 decreases among more educated people. The
      family doctor was the main source of information when people wanted to be
      immunized against seasonal flu (OR = 1.43) and A/H1N1 (OR = 2.47). CONCLUSIONS:
      Low acceptance of the pandemic vaccination and low perceived severity of
      influenza A/H1N1. Previous vaccination experience with seasonal flu creates a
      predisposition to immunization against A/H1N1. Although the media were the
      leading source of information during this period, the family doctor's influence
      on their decision to be vaccinated was significant.

PMID- 22948427
TI  - [Aspirin in the primary prevention of colorectal cancer].
AB  - Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have been
      associated with a reduction in the risk of developing adenomas and colorectal
      cancer. The available scientific evidence justifies the need for more studies
      that evaluate the protective effect of aspirin and other NSAIDs as a preventive
      measure against cancer of the colon; define the minimum efficient dosage; the age
      at which to begin treatment; the most convenient duration of the latter; and the
      sub-populations for which the benefits of chemoprophylaxis outweigh possible
      adverse effects.

PMID- 22948428
TI  - [The public image of nursing: a profession to learn about].
AB  - Nursing is a profession that has suffered from public stereotyping for a long
      time. It has been viewed historically as a female profession, under the orders of
      doctors and without its own field of competence. Major changes have occurred in
      the discipline over the last decade that directly affect the profession. As a
      result, this review of the literature has tried to identify the image of nursing
      held by the population, the prevailing stereotypes related to it, and what the
      public considers that nurses do. Eight categories emerged from the thematic
      analysis that can help in explaining the view that society has of nursing and the
      evolution it has undergone. It seems that the public is predominantly ignorant of
      the essence and focus of the discipline, which is none other than care of the
      person, family or community. It is also a little known profession as society does
      not fully acknowledge that nurses have their own field of competence, autonomy
      and independence. There is still a tendency to consider nursing as a profession
      inferior to medicine, closely related to "tasks", and there is trust in its
      carrying out those activities that have been traditionally associated with it.
      However, it is coming to be perceived as a profession that is less related to
      femininity and that involves greater preparation than in the past.

PMID- 22948429
TI  - [Monogenic human obesity: role of the leptin-melanocortin system in the
      regulation of food intake and body weight in humans].
AB  - Human obesity is a disorder of multifactorial origin in which genetic and
      environmental factors are involved. To understand the mechanisms regulating
      energy intake and fat accumulation in the body, it is important to study the
      genetic alterations causing monogenic obesity.  Most of the genes involved in
      monogenic obesity are associated with the leptin-melanocortin system; hence the
      importance of studying this system by analysing natural mutations in mice.
      Previous studies have described mutations in leptin and its receptor,
      proopiomelanocortin and prohormone convertase 1 associated with human obesity of
      monogenic origin. The aim of this study is to provide an updated review of the
      main characteristics and functioning of the leptin-melanocortin system, and its
      implications and potentialities in regulating food intake and body weight.

PMID- 22948430
TI  - [The impact of Hungtinton's disease on the family].
AB  - This article describes the structural and emotional disturbances in families with
      one or more members affected by Huntington's disease, according to the different
      symptoms, the affected member (offspring, parent) and the different stages of the
      disease. We consider that support services to the family should be made up of
      professionals who are specialists in the specific needs of the disease and who
      should help to plan and design individual, suitable and flexible support. This
      support should focus on overcoming the impact of the disease, providing relevant
      information, seeking practical solutions, giving emotional support, designing
      specific care in each case and each stage, and reducing fear of the future.

PMID- 22948431
TI  - [Surgical treatment of extralobar pulmonary sequestration diagnosed prenatally].

PMID- 22948432
TI  - [Semicircular lipoatrophy. The case of a very tall worker].

PMID- 22948433
TI  - Intravenous lipoma and pulmonary sarcoidosis treated with prednisone.
AB  - Corticosteroid-induced lipomatosis is not a rare condition, but lipoma in the
      central veins has scarcely been described. According to the databases consulted,
      this is the first report of a lipoma within the central veins coexistent with
      long-term use of corticosteroid. It involved a 47-year-old male under treatment
      for pulmonary sarcoidosis with prednisone. Computerized tomography of the thorax
      was performed and incidentally the images showed a mass within the central veins
      with the characteristics of lipoma. He was asymptomatic and refused surgical
      procedures. The intraluminal lipoma originated in the right brachiocephalic and
      subclavian veins. Control tomography showed a slow development of this lipoma,
      without obstructive effects or malignant features. Oral prednisone was changed
      for methotrexate. The patient is asymptomatic and under longstanding out-patient
      surveillance. Corticosteroid treatments for sarcoidosis can play a role in the
      development of intravascular lipoma, but this association is not well defined.
      Case reports could contribute to clarifying whether this relationship is causal
      or merely casual.

PMID- 22948434
TI  - [Penetrating ascending aortic ulcer in an asymptomatic patient].
AB  - Penetrating aortic ulcer (PAU) has been defined as an atherosclerotic plaque
      ulceration that breaks the internal elastic lamina of the aorta, which may
      progress to a wall hematoma or aortic dissection in the case of blood seeping
      into the middle layer. Although PAU is commonly located in the descending aorta,
      the involvement of the ascending aorta can be fatal. Therefore, surgery is
      indicated even in asymptomatic patients presenting an ascending PAU. We report on
      an asymptomatic patient with ascending PAU referred for replacement of the
      ascending aorta with a composite prosthetic graft.

PMID- 22948435
TI  - [MRI in the diagnostic and evolutive control of subacute combined degeneration. A
      case report].
AB  - A deficit of vitamin B12, generally resulting from pernicious anaemia, can give
      rise to disorders of the spinal cord, brain, optic and peripheral nerves. The
      principal neurological syndrome is subacute combined degeneration of the spinal
      cord (SCD), which can cause progressive motor and/or sensitive alterations,
      instability and incontinency, due to the demyelination of the posterior horn of
      the spinal cord. The identification by magnetic resonance (MR) of signal
      hyperintensity in T2 weighted sequences at the level of the posterior horns of
      the spinal and/or cervical cord can be of great use in diagnosising the patient
      with SCD, above all when the symptoms are mild or nonspecific, and the patient
      does not have haematological or gastrointestinal alterations. Besides, the
      evolution of the altered signal of the posterior horns in MR can be of use in
      evaluating the efficacy of treatment, since their normalization is related to
      clinical improvement.

PMID- 22948436
TI  - [Oesophageal leiomyoma: VATS (video-assisted thoracic surgery) resection].
AB  - Leiomyomas are the most common benign tumours of the oesophagus. The most
      frequent symptoms are dysphagia and epigastric pain, although 50% of patients
      remain asymptomatic and the tumour is sometimes discovered incidentally. We
      report a case of oesophageal leiomyoma with emphasis on the operative management
      by VATS. Traditionally, operative management by transthoracic enucleation is the
      procedure of choice. In this study we present our experience using a minimally
      invasive approach.

PMID- 22948438
TI  - Identification of RFLP and NBS/PK profiling markers for disease resistance loci
      in genetic maps of oats.
AB  - Two of the domains most widely shared among R genes are the nucleotide binding
      site (NBS) and protein kinase (PK) domains. The present study describes and maps
      a number of new oat resistance gene analogues (RGAs) with two purposes in mind:
      (1) to identify genetic regions that contain R genes and (2) to determine whether
      RGAs can be used as molecular markers for qualitative loci and for QTLs affording
      resistance to Puccinia coronata. Such genes have been mapped in the diploid A.
      strigosa * A. wiestii (Asw map) and the hexaploid MN841801-1 * Noble-2 (MN map).
      Genomic and cDNA NBS-RGA probes from oat, barley and wheat were used to produce
      RFLPs and to obtain markers by motif-directed profiling based on the NBS (NBS
      profiling) and PK (PK profiling) domains. The efficiency of primers used in
      NBS/PK profiling to amplify RGA fragments was assessed by sequencing individual
      marker bands derived from genomic and cDNA fragments. The positions of 184
      markers were identified in the Asw map, while those for 99 were identified in the
      MN map. Large numbers of NBS and PK profiling markers were found in clusters
      across different linkage groups, with the PK profiling markers more evenly
      distributed. The location of markers throughout the genetic maps and the
      composition of marker clusters indicate that NBS- and PK-based markers cover
      partly complementary regions of oat genomes. Markers of the different classes
      obtained were found associated with the two resistance loci, PcA and R-284B-2,
      mapped on Asw, and with five out of eight QTLs for partial resistance in the MN
      map. 53 RGA-RFLPs and 187 NBS/PK profiling markers were also mapped on the
      hexaploid map A. byzantina cv. Kanota * A. sativa cv. Ogle. Significant co
      localization was seen between the RGA markers in the KO map and other markers
      closely linked to resistance loci, such as those for P. coronata and barley
      yellow dwarf virus (Bydv) that were previously mapped in other segregating
      populations.

PMID- 22948437
TI  - Accessing complex crop genomes with next-generation sequencing.
AB  - Many important crop species have genomes originating from ancestral or recent
      polyploidisation events. Multiple homoeologous gene copies, chromosomal
      rearrangements and amplification of repetitive DNA within large and complex crop
      genomes can considerably complicate genome analysis and gene discovery by
      conventional, forward genetics approaches. On the other hand, ongoing
      technological advances in molecular genetics and genomics today offer
      unprecedented opportunities to analyse and access even more recalcitrant genomes.
      In this review, we describe next-generation sequencing and data analysis
      techniques that vastly improve our ability to dissect and mine genomes for causal
      genes underlying key traits and allelic variation of interest to breeders. We
      focus primarily on wheat and oilseed rape, two leading examples of major
      polyploid crop genomes whose size or complexity present different, significant
      challenges. In both cases, the latest DNA sequencing technologies, applied using
      quite different approaches, have enabled considerable progress towards
      unravelling the respective genomes. Our ability to discover the extent and
      distribution of genetic diversity in crop gene pools, and its relationship to
      yield and quality-related traits, is swiftly gathering momentum as DNA sequencing
      and the bioinformatic tools to deal with growing quantities of genomic data
      continue to develop. In the coming decade, genomic and transcriptomic sequencing,
      discovery and high-throughput screening of single nucleotide polymorphisms,
      presence-absence variations and other structural chromosomal variants in diverse
      germplasm collections will give detailed insight into the origins, domestication
      and available trait-relevant variation of polyploid crops, in the process
      facilitating novel approaches and possibilities for genomics-assisted breeding.

PMID- 22948439
TI  - The association between psychosocial and medical factors with long-term sexual
      dysfunction after treatment for colorectal cancer.
AB  - PURPOSE: Colorectal cancer patients usually receive treatments (e.g., pelvic
      surgery or radiotherapy, colostomy) that increase their risk for sexual problems.
      Previous research has mainly focused on demographic and medical risk factors.
      Because little is known about the role of psychosocial variables in sexual
      dysfunction, this research sought to identify the contribution of demographic,
      medical, and psychosocial factors to sexual dysfunction using multivariate
      analyses. METHODS: Male and female colorectal cancer survivors (N = 261; mean,
      2.5 years post-treatment) completed paper-pencil questionnaires assessing sexual
      function, psychosocial variables (e.g., depression, social support, body image,
      and dyadic adjustment), and demographics. Medical information was obtained from
      patients' self-report and medical records. RESULTS: Multiple regression analyses
      revealed that older age, having received destructive surgery (i.e.,
      abdominoperineal resection), and poor social support were uniquely and
      significantly associated with low international index of erectile function scores
      in men. For women, low female sexual function index scores were significantly
      associated with older age and poor global quality of life. Men, but not women,
      with rectal cancer reported worse sexual function compared to those with colon
      cancer. CONCLUSIONS: Sexual dysfunction after colorectal cancer treatment is
      related to demographic, medical, and psychosocial factors. These associations can
      help to identify patients at high risk of sexual problems in order to assist
      restoring sexual functioning if desired.

PMID- 22948440
TI  - From 'implications' to 'dimensions': science, medicine and ethics in society.
AB  - Much bioethical scholarship is concerned with the social, legal and philosophical
      implications of new and emerging science and medicine, as well as with the
      processes of research that under-gird these innovations. Science and technology
      studies (STS), and the related and interpenetrating disciplines of anthropology
      and sociology, have also explored what novel technoscience might imply for
      society, and how the social is constitutive of scientific knowledge and
      technological artefacts. More recently, social scientists have interrogated the
      emergence of ethical issues: they have documented how particular matters come to
      be regarded as in some way to do with 'ethics', and how this in turn enjoins
      particular types of social action. In this paper, I will discuss some of this and
      other STS (and STS-inflected) literature and reflect on how it might complement
      more 'traditional' modes of bioethical enquiry. I argue that STS might (1) cast
      new light on current bioethical issues, (2) direct the gaze of bioethicists
      towards matters that may previously have escaped their attention, and (3)
      indicate the import not only of the ethical implications of biomedical
      innovation, but also how these innovative and other processes feature ethics as a
      dimension of everyday laboratory and clinical work. In sum, engagements between
      STS and bioethics are increasingly important in order to understand and manage
      the complex dynamics between science, medicine and ethics in society.

PMID- 22948441
TI  - What's the point of philosophical bioethics?
AB  - Many people working in bioethics take pride in the subject's embrace of a wide
      range of disciplines. This invites questions of what in particular is added by
      each. In this paper, I focus on the role of philosophy within the field: what, if
      anything, is its unique contribution to bioethics? I sketch out a claim that
      philosophy is central to bioethics because of its particular analytic abilities,
      and defend its place within bioethics from a range of sceptical attacks.

PMID- 22948442
TI  - Omalizumab protects against allergen- induced bronchoconstriction in allergic
      (immunoglobulin E-mediated) asthma.
AB  - BACKGROUND: Omalizumab has been shown to suppress responses to inhaled allergens
      in allergic asthma patients with pretreatment immunoglobulin E (IgE) <=700 IU/ml.
      To extend current dosing tables, we evaluated the potential of high omalizumab
      doses to block allergen-induced bronchoconstriction in patients with higher IgE
      levels. METHODS: Asthmatic adults (18-65 years; body weight 40-150 kg) were
      divided into groups according to screening IgE (group 1: 30-300 IU/ml; group 2:
      700-2,000 IU/ml) and randomized 2:1 to omalizumab/placebo every 2 or 4 weeks for
      12-14 weeks. Allergen bronchoprovocation (ABP) testing was performed before
      treatment and at weeks 8 and 16. The primary efficacy endpoint, the early-phase
      allergic response (EAR), was defined as the maximum percentage drop in forced
      expiratory volume in 1 s during the first 30 min after ABP. Serum free IgE was
      determined as a pharmacodynamic endpoint, and the exhaled fractional
      concentration of nitric oxide (FE(NO)) was an exploratory endpoint. RESULTS:
      Fifty patients were included in the study. Omalizumab improved EAR; at week 8,
      EAR was 23.1% for placebo, 9.3% in group 1 (p = 0.018 versus placebo) and 5.6% in
      group 2 (p < 0.001). At week 16, EAR was 20%, 11.8% (p = 0.087) and 5.1% (p <
      0.001), respectively. Free IgE decreased in groups 1 and 2 and remained <50 ng/ml
      in all patients during weeks 6-16. Omalizumab completely suppressed FE(NO)
      increases after ABP in both groups. CONCLUSIONS: Omalizumab blocked early
      asthmatic responses over a broad range of IgE/body weight combinations. Extending
      the dosing tables enables omalizumab to benefit a wider range of patients.

PMID- 22948443
TI  - Clinical practice guidelines on wait-listing for kidney transplantation: 
      consistent and equitable?
AB  - BACKGROUND: Apparent variability in wait-listing criteria globally has raised
      concern about inequitable access to kidney transplantation. This study aimed to
      compare the quality, the scope, and the consistency of international guidelines
      on wait-listing for kidney transplantation. METHODS: Electronic databases and
      guideline registries were searched to December 2011. The Appraisal of Guidelines
      for Research and Evaluation II instrument and textual synthesis was used to
      assess and compare recommendations. RESULTS: Fifteen guidelines published from
      2001 to 2011 were included. Methodological rigor and scope were variable. We
      identified 4 major criteria across guidelines: recipient age and life expectancy,
      medical criteria, social and lifestyle circumstances, and psychosocial
      considerations. Whereas some recommendations were consistent, there were
      differences in age cutoffs, estimated life expectancy (2-5 years), and glomerular
      filtration rate at listing (15-20 mL/min/1.73 m). Cardiovascular
      contraindications were broadly defined. Recommended cancer-free periods also
      varied substantially, and whereas uncontrolled infections were universally
      contraindicated, human immunodeficiency virus thresholds and adherence to highly
      active antiretroviral therapy were inconsistent. Most guidelines recommended
      psychological screening but were not augmented with specific clinical assessment
      tools. CONCLUSIONS: Wait-listing recommendations in current guidelines are based
      on life expectancy, comorbidities, lifestyle, and psychosocial factors. Some
      recommendations are different across guidelines or broadly defined. There is a
      case for developing comprehensive, methodologically robust, and regularly updated
      guidelines on wait-listing for kidney transplantation.

PMID- 22948444
TI  - A clinically feasible approach to induce delayed tolerance in recipients of prior
      kidney or vascularized composite allotransplants.
AB  - BACKGROUND: Mixed chimerism induces donor-specific tolerance to kidney and
      vascularized composite allotransplants (VCA). However, simultaneous kidney or VCA
      and bone marrow transplantation (BMT) is problematic because of the combined risk
      and time required for conditioning. Here, we developed a delayed tolerance
      induction strategy with mixed chimerism through BMT in prior kidney or VCA
      recipients. METHODS: Wistar Furth rats that received kidney transplantation (KTx)
      or VCA from allogeneic August-Copenhagen Irish donors were maintained on
      immunosuppression (IS) for 8 weeks. These recipients were then conditioned with
      anti-alphabeta-T-cell receptor and anti-CD8 monoclonal antibodies, total body
      irradiation, cyclosporine A and mycophenolate mofetil (12 doses), and
      antilymphocyte serum (one dose); and transplanted with T-cell-depleted donor
      marrow. All IS was discontinued on day 11 after BMT. RESULTS: Cyclosporine A
      monotherapy prevented acute rejection of KTx or VCA. However, all allografts were
      rejected after IS withdrawal in KTx or VCA recipients who were conditioned but
      did not receive BMT. After delayed BMT, mixed chimerism was initially achieved in
      all KTx or VCA recipients with 200-, 300-, and 400-cGy total body irradiation.
      Long-term tolerance to KTx or VCA was achieved in most of these recipients with
      total IS withdrawal. The tolerance achieved with delayed BMT was donor specific
      as confirmed by acceptance of donor skin and rejection of third-party skin graft.
      CONCLUSIONS: IS-free donor-specific tolerance can be successfully induced with
      delayed BMT to previous recipients of kidney transplantation or VCA. These
      findings have significant clinical implications for transplant recipients who
      receive an organ from either a living donor or a deceased donor with frozen bone
      marrow cells available.

PMID- 22948445
TI  - Distance measurements between boron and carbon at natural abundance using magic
      angle spinning REAPDOR NMR and a universal curve.
AB  - The rotational echo adiabatic passage double resonance (REAPDOR) magic angle
      spinning NMR experiment efficiently recouples the dipolar interaction between a
      spin-1/2 and a spin >1/2, enabling accurate and efficient measurement of their
      inter-nuclear distance. We demonstrate that under adiabatic conditions a
      universal curve that depends only on the inter-nuclear distance fits the REAPDOR
      recoupling curve for a (13)C (spin-1/2)-(11)B (spin-3/2) spin pair. In 4
      (hydroxymethyl)phenylboronic acid MIDA ester the inter-nuclear distance between
      the methyl carbon and boron was determined to be 2.76 +/- 0.14 A, in agreement
      with the distance of 2.68 A determined by X-ray crystallography. Similar
      experiments performed at two different spinning speeds and fit simultaneously to
      the same curve give a distance of 2.73 A and distances to other carbons in the
      molecule are also determined. The low abundance of carbon-13 at natural abundance
      (1.1%) and the reduced abundance of boron-11 (80.1%) render the experiment
      insensitive to (13)C-(13)C homonuclear couplings and significantly reduce the
      effect of a second boron nucleus at a longer distance. This approach can be
      extended to any spin-3/2 coupled to a spin-1/2.

PMID- 22948446
TI  - Effects of salidroside on exhaustive exercise-induced oxidative stress in rats.
AB  - Intense exercise increases oxygen consumption and may produce an imbalance
      between reactive oxygen species (ROS) and antioxidants, inducing oxidative stress
      as a result of increased ROS production. Exogenous antioxidants may prevent
      oxidative damages since they are able to detoxify certain peroxides by scavenging
      the ROS produced during exercise. The aim of this study was to evaluate the
      effects of salidroside on exhaustive exercise-induced oxidative stress in rats. A
      total of 40 animals were randomly divided into four groups of ten rats each:
      control (C), low-dose salidroside-treated (LT), middle-dose salidroside-treated
      (MT) and high-dose salidroside-treated (HT) groups. The rats in the treated
      groups received salidroside (25, 50 and 100 mg/kg, respectively) intragastrically
      (ig) and the rats in the control group received drinking water ig for 4 weeks.
      After 4 weeks, the rats performed an exhaustive swimming exercise and exhaustive
      swimming times were recorded. The malondialdehyde (MDA), catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glycogen levels
      in the liver tissues of the rats were measured. The data revealed that
      salidroside was able to elevate the exercise tolerance and increase the liver
      glycogen levels of the rats following exhaustive exercise. Salidroside was also
      able to reduce MDA levels and enhance the activities of antioxidant enzymes (CAT,
      SOD and GSH-Px) in the liver tissues of the rats. The results from this study
      indicate that salidroside is effective in the prevention of oxidative stress
      following exhaustive exercise.

PMID- 22948447
TI  - Oral contraceptives do not affect muscle strength and hop performance in active
      women.
AB  - OBJECTIVE: The primary aim of this study was to compare muscle strength in the
      upper and lower limb, as well as hop performance during oral contraceptive (OC)
      use with non-OC use in the same woman. A secondary aim was to compare muscle
      strength and hop performance within 3 specific phases of an OC cycle, as well as
      during a menstrual cycle of the corresponding cycle days (non-OC cycle). DESIGN:
      Crossover. SETTING: Research laboratory. PARTICIPANTS: Seventeen moderate to
      highly recreationally active women participated in the study. INTERVENTION:
      Observational study with no intervention. MAIN OUTCOME MEASURES: Maximal
      isokinetic muscle strength of knee extensors, isometric handgrip strength, and 1
      leg hop test for distance were measured during 1 OC cycle and 1 non-OC cycle at 3
      specific phases, respectively, using a crossover design. RESULTS: No significant
      differences were found in terms of muscle strength and hop performance between
      the OC cycle and the non-OC cycle. Furthermore, no significant difference in
      muscle strength and hop performance could be demonstrated within the OC cycle or
      within the phases of the menstrual cycle except from maximal isokinetic muscle
      strength in the knee extensors detected between the early follicular phase and
      the luteal phase. CONCLUSIONS: We found no support for any significant influence
      of OC use on muscle strength and hop performance in healthy moderately active
      women.

PMID- 22948448
TI  - Iron deficiency in adolescent female athletes - is iron status affected by
      regular sporting activity?
AB  - OBJECTIVE: To determine the prevalence of iron deficiency (ID) and iron
      deficiency anemia (IDA) among a group of female athletes and compare with an age
      matched group of female nonathletes. To study lifestyle factors that could play a
      role in the development of ID and IDA and compare these factors between the
      groups. DESIGN: A controlled clinical trial. SETTING: A senior high school for
      athletes in Gothenburg, Sweden. PARTICIPANTS: All female athletes at a senior
      high school for top-level athletes were offered to take part. Fifty-seven female
      athletes accepted to participate in the study. The control group consisted of a
      random sample of 130 age-matched nonathlete students; 92 accepted to participate
      in the study. INTERVENTION: Intervention was not an actual part of this study but
      those with ID and IDA were treated with iron by the regular school doctor. MAIN
      OUTCOME MEASURES: Iron deficiency anemia and ID were determined by levels of
      hemoglobin, serum iron, total iron-binding capacity, transferrin saturation, and
      serum ferritin. RESULTS: The main result of the study is the finding that ID and
      IDA are common among young adolescent female athletes and that there was no
      difference between female athletes and nonathletes. In the athlete group, 30 of
      57 individuals (52%) had ID compared with 43 of 92 individuals (48%) in the
      nonathlete group (P > 0.3). Comparisons of the 2 groups showed no significant
      difference in hemoglobin (P > 0.30). In total, we found that 5 of 57 athletes
      (8.6%) had IDA compared with 3 of 92 nonathletes (3.3%), the difference being not
      statistically significant (P = 0.24). CONCLUSIONS: The main finding of this study
      is that ID and IDA are common among female adolescents but not more common among
      athletes than nonathletes. The results are despite factors that should favor a
      better iron status in the athlete group, such as better iron intake and less
      menstrual bleeding. Other factors that might have an impact on iron balance, must
      therefore be considered.

PMID- 22948449
TI  - Impact of changes in anti-doping regulations (WADA Guidelines) on asthma care in
      athletes.
AB  - OBJECTIVE: To investigate how changes to the World Anti-Doping Agency (WADA)
      guidelines on asthma medication requests have impacted the management of
      asthmatic athletes in Portugal. DESIGN: Retrospective analysis of asthma
      medication requests submitted in 2008 to 2010. SETTING: Portuguese Anti-Doping
      Authority database. PARTICIPANTS: Athletes requesting the use of inhaled
      corticosteroids and/or beta2-agonists. INDEPENDENT VARIABLES: Demographic,
      therapeutic, and diagnostic test data. MAIN OUTCOME MEASURES: Yearly changes in
      number of asthma medication requests and diagnostic procedures. RESULTS: We
      analyzed 326 requests: 173 abbreviated Therapeutic Use Exemptions (TUEs) in 2008
      (objective tests not required), 9 Declaration of Use (DoU) and 76 TUEs in 2009,
      and 39 DoU and 29 TUEs in 2010. Spirometry was performed in 87% and 37% of
      athletes in 2009 and 2010, respectively; the corresponding figures for
      bronchoprovocation were 59% and 16%, almost all positive in both years.
      CONCLUSIONS: Applications for inhaler use have decreased by approximately half
      since objective asthma testing became mandatory. Our findings show that WADA
      guidelines have an impact on asthmatic athletes care: In 2009 a more rigorous
      screening was possible, leading to withdrawal of unnecessary medication. Constant
      changes, however, jeopardize this achievement and nowadays introduce safety
      issues stemming from the unsupervised use of inhaled beta2-agonists.

PMID- 22948450
TI  - Pediatrics in Clinics: highlights.

PMID- 22948451
TI  - Carotid stenosis: what is the high-risk population?
AB  - OBJECTIVE: Prevention is the best treatment for cerebrovascular disease, which is
      why early diagnosis and the immediate treatment of carotid stenosis contribute
      significantly to reducing the incidence of stroke. Given its silent nature, 80%
      of stroke cases occur in asymptomatic individuals, emphasizing the importance of
      screening individuals with carotid stenosis and identifying high-risk groups for
      the disease. The aim of this study was to determine the prevalence and the most
      frequent risk factors for carotid stenosis. METHODS: A transversal study was
      conducted in the form of a stroke prevention campaign held on three
      nonconsecutive Saturdays. During the sessions, carotid stenosis diagnostic
      procedures were performed for 500 individuals aged 60 years or older who had
      systemic arterial hypertension and/or diabetes mellitus and/or coronary heart
      disease and/or a family history of stroke. RESULTS: The prevalence of carotid
      stenosis in the population studied was 7.4%, and the most frequent risk factors
      identified were mean age of 70 years, carotid bruit, peripheral obstructive
      arterial disease, coronary insufficiency and smoking. Independent predictive
      factors of carotid stenosis include the presence of carotid bruit or peripheral
      obstructive arterial disease [corrected] and/or coronary insufficiency.
      CONCLUSIONS: The population with peripheral obstructive arterial disease
      [corrected] and/or coronary insufficiency and carotid bruit should undergo
      routine screening for carotid stenosis.

PMID- 22948452
TI  - Sexual function after anterior vaginal wall prolapse surgery.
AB  - OBJECTIVE: The aim of this study was to compare female sexual function after
      surgical treatment of anterior vaginal prolapse with either small intestine
      submucosa grafting or traditional colporrhaphy. METHODS: Subjects were randomly
      assigned, preoperatively, to the small intestine submucosa graft (n = 29) or
      traditional colporrhaphy (n = 27) treatment group. Postoperative outcomes were
      analyzed at 12 months. The Female Sexual Function Index questionnaire was used to
      assess sexual function. Data were compared with independent samples or a paired
      Student's t-test. RESULTS: In the small intestine submucosa group, the total mean
      Female Sexual Function Index score increased from 15.5+/-7.2 to 24.4+/-7.5
      (p<0.001). In the traditional colporrhaphy group, the total mean Female Sexual
      Function Index score increased from 15.3+/-6.8 to 24.2+/-7.0 (p<0.001).
      Improvements were noted in the domains of desire, arousal, lubrication, orgasm,
      satisfaction, and pain. There were no differences between the two groups at the
      12-month follow-up. CONCLUSIONS: Small intestine submucosa repair and traditional
      colporrhaphy both improved sexual function postoperatively. However, no
      differences were observed between the two techniques.

PMID- 22948453
TI  - The effects of angiotensin-converting enzyme inhibitors on peritoneal protein
      loss and solute transport in peritoneal dialysis patients.
AB  - OBJECTIVE: The objective of this study was to examine the effects of angiotensin
      converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein
      loss, and proteinuria in peritoneal dialysis patients. METHODS: Fifty-four
      peritoneal dialysis patients were included in the study. The patients were
      divided into two groups. Group 1 (n = 34) was treated with angiotensin-converting
      enzyme inhibitors. Group 2 (n = 20) did not receive any antihypertensive drugs
      during the entire follow-up. Eleven patients were excluded from the study
      thereafter. Thus, a total of 30 patients in Group 1 and 13 patients in Group 2
      completed the study. We observed the patients for six months. Group 1 patients
      received maximal doses of angiotensin-converting enzyme inhibitors for six
      months. Parameters at the beginning of study and at the end of six months were
      evaluated. RESULTS: At the end of six months, total peritoneal protein loss in 24
      hour dialysate effluent was significantly decreased in Group 1, whereas it was
      increased in Group 2. Compared to the baseline level, peritoneal albumin loss in
      24-hour dialysate effluent and 4-hour D/P creatinine were significantly increased
      in Group 2 but were not significantly changed in Group 1. A covariance analysis
      between the groups revealed a significant difference only in the decreased amount
      of total protein loss in 24-hour dialysate. Proteinuria was decreased
      significantly in Group 1. CONCLUSION: This study suggests that angiotensin
      converting enzyme inhibitors reduce peritoneal protein loss and small-solute
      transport and effectively protect peritoneal membrane transport in peritoneal
      dialysis patients.

PMID- 22948454
TI  - Skeletal muscle major histocompatibility complex class I and II expression
      differences in adult and juvenile dermatomyositis.
AB  - OBJECTIVE: To analyze major histocompatibility complex expression in the muscle
      fibers of juvenile and adult dermatomyositis. METHOD: In total, 28 untreated
      adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and
      Peter's criteria) and a control group consisting of four dystrophic and five
      Pompe's disease patients were analyzed. Routine histological and
      immunohistochemical (major histocompatibility complex I and II,
      StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle
      sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased
      connective tissue were analyzed relative to the expression of major
      histocompatibility complexes I and II, which were assessed as negatively or
      positively stained fibers in 10 fields (200X). RESULTS: The mean ages at disease
      onset were 42.0+/-15.9 and 7.3+/-3.4 years in adult and juvenile dermatomyositis,
      respectively, and the symptom durations before muscle biopsy were similar in both
      groups. No significant differences were observed regarding gender, ethnicity and
      frequency of organ involvement, except for higher creatine kinase and lactate
      dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a
      significantly higher frequency of major histocompatibility complex I (96.4% vs.
      50.0%, p<0.001) compared with major histocompatibility complex II expression
      (14.3% vs. 53.6%, p=0.004) was observed in juvenile dermatomyositis. Fiber damage
      (p=0.006) and increased connective tissue (p<0.001) were significantly higher in
      adult dermatomyositis compared with the presence of perifascicular atrophy
      (p<0.001). The results of the histochemical and histological data did not
      correlate with the demographic data or with the clinical and laboratory features.
      CONCLUSION: The overexpression of major histocompatibility complex I was an
      important finding for the diagnosis of both groups, particularly for juvenile
      dermatomyositis, whereas there was lower levels of expression of major
      histocompatibility complex II than major histocompatibility complex I. This
      finding was particularly apparent in juvenile dermatomyositis.

PMID- 22948455
TI  - Predicting dysthyroid optic neuropathy using computed tomography volumetric
      analyses of orbital structures.
AB  - OBJECTIVE: To evaluate the ability of orbital apex crowding volume measurements
      calculated with multidetector-computed tomography to detect dysthyroid optic
      neuropathy. METHODS: Ninety-three patients with Graves' orbitopathy were studied
      prospectively. All of the patients underwent a complete neuro-ophthalmic
      examination and computed tomography scanning. Volumetric measurements were
      calculated from axial and coronal contiguous sections using a dedicated
      workstation. Orbital fat and muscle volume were estimated on the basis of their
      attenuation values (in Hounsfield units) using measurements from the anterior
      orbital rim to the optic foramen. Two indexes of orbital muscle crowding were
      calculated: i) the volumetric crowding index, which is the ratio between soft
      tissue (mainly extraocular muscles) and orbital fat volume and is based on axial
      scans of the entire orbit; and ii) the volumetric orbital apex crowding index,
      which is the ratio between the extraocular muscles and orbital fat volume and is
      based on coronal scans of the orbital apex. Two groups of orbits (with and
      without dysthyroid optic neuropathy) were compared. RESULTS: One hundred and two
      orbits of 61 patients with Graves' orbitopathy met the inclusion criteria and
      were analyzed. Forty-one orbits were diagnosed with Graves' orbitopathy, and 61
      orbits did not have optic neuropathy. The two groups of orbits differed
      significantly with regard to both of the volumetric indexes (p<0.001). Although
      both indexes had good discrimination ability, the volumetric orbital apex
      crowding index yielded the best results with 92% sensitivity, 86% specificity,
      81%/94% positive/negative predictive value and 88% accuracy at a cutoff of 4.14.
      CONCLUSION: This study found that the orbital volumetric crowding index was a
      more effective predictor of dysthyroid optic neuropathy than previously described
      computed tomography indexes were.

PMID- 22948456
TI  - Effects of arterial oxygen tension and cardiac output on venous saturation: a
      mathematical modeling approach.
AB  - OBJECTIVES: Hemodynamic support is aimed at providing adequate O2 delivery to the
      tissues; most interventions target O2 delivery increase. Mixed venous O2
      saturation is a frequently used parameter to evaluate the adequacy of O2
      delivery. METHODS: We describe a mathematical model to compare the effects of
      increasing O2 delivery on venous oxygen saturation through increases in the
      inspired O2 fraction versus increases in cardiac output. The model was created
      based on the lungs, which were divided into shunted and non-shunted areas, and on
      seven peripheral compartments, each with normal values of perfusion, optimal
      oxygen consumption, and critical O2 extraction rate. O2 delivery was increased by
      changing the inspired fraction of oxygen from 0.21 to 1.0 in steps of 0.1 under
      conditions of low (2.0 L.min(-1)) or normal (6.5 L.min(-1)) cardiac output. The
      same O2 delivery values were also obtained by maintaining a fixed O2 inspired
      fraction value of 0.21 while changing cardiac output. RESULTS: Venous oxygen
      saturation was higher when produced through increases in inspired O2 fraction
      versus increases in cardiac output, even at the same O2 delivery and consumption
      values. Specifically, at high inspired O2 fractions, the measured O2 saturation
      values failed to detect conditions of low oxygen supply. CONCLUSIONS: The mode of
      O2 delivery optimization, specifically increases in the fraction of inspired
      oxygen versus increases in cardiac output, can compromise the capability of the
      "venous O2 saturation" parameter to measure the adequacy of oxygen supply.
      Consequently, venous saturation at high inspired O2 fractions should be
      interpreted with caution.

PMID- 22948457
TI  - M2-polarized macrophages promote metastatic behavior of Lewis lung carcinoma
      cells by inducing vascular endothelial growth factor-C expression.
AB  - OBJECTIVES: Tumor-associated macrophages that generally exhibit an alternatively
      activated (M2) phenotype have been linked to tumor progression and metastasis.
      However, the role of M2-polarized macrophages in the growth and metastasis of
      lung adenocarcinoma remains enigmatic. The aim of this study was to explore the
      effect of M2 macrophages on the proliferation and migration of mouse Lewis lung
      carcinoma cells and tumor-induced lymphangiogenesis. METHODS: Trypan blue
      staining and the Transwell migration assay were performed to evaluate the effects
      of activated (M1 or M2) macrophages on the proliferation and migration of Lewis
      cells. Furthermore, vascular endothelial growth factor-C expression in Lewis
      cells and nitric oxide secretion from activated macrophages were detected during
      the co-culture assay. Following treatment with activated macrophages, lymphatic
      endothelial cells differentiated into capillary-like structures, and the
      induction of Lewis cell migration was assessed using a two-dimensional Matrigel
      based assay. RESULTS: In the co-culture Transwell system, the proliferation and
      migration of Lewis cells were promoted by M2 macrophages. Moreover, the co
      culture significantly increased the expression of vascular endothelial growth
      factor-C by Lewis cells and reduced the secretion of nitric oxide from M2
      macrophages, which subsequently led to the capillary morphogenesis of lymphatic
      endothelial cells. Interestingly, following co-culture with Lewis cells, the
      function of RAW264.7 cells was polarized toward that of the M2 macrophage
      phenotype. CONCLUSION: M2-polarized macrophages promoted the metastatic behavior
      of Lewis cells by inducing vascular endothelial growth factor-C expression. Thus,
      the interruption of signaling between M2 macrophages and Lewis cells may be
      considered to be a new therapeutic strategy.

PMID- 22948458
TI  - Laparoscopic nephrectomy for xanthogranulomatous pyelonephritis--are there
      predictive factors for success?
AB  - OBJECTIVES: Laparoscopic nephrectomy for xanthogranulomatous pyelonephritis is
      currently associated with great operative difficulty and surgical complications.
      Herein, we report on our single-center experience and describe predictive factors
      for successfully accomplishing this procedure. METHOD: Between March 1998 and
      April 2010, 66 patients (27 men and 39 women) underwent laparoscopic nephrectomy
      for the treatment of a unilateral nonfunctioning kidney. These patients had
      previous diagnoses of renal chronic inflammation associated with calculi and
      previous pyonephrosis. All of the nephrectomies were performed using the
      transperitoneal approach, and a similar technique was used for radical
      nephrectomy. RESULTS: Laparoscopic nephrectomy for the treatment of renal chronic
      inflammation was successful in 58/66 cases (87.9%). Eight cases were converted to
      the open technique because of difficulty in progression, which was related to the
      discovery of dense adhesions in the hilar or perirenal region. One major (colonic
      lesion) and two minor (wound infection) complications occurred in the conversion
      group. A diagnosis of xanthogranulomatous pyelonephritis was confirmed
      pathologically for all of the specimens. Of the factors examined, a longitudinal
      renal length greater than 12 cm (laparoscopy group - 7.2+/-1.8 cm, versus open
      group - 13.6+/-1.5 cm; p<0.05) and time to access the renal vessels (laparoscopy
      group - 32+/-18 min, versus open group - 91+/-11 min; p<0.05) were associated
      with a higher conversion rate. Although the number of patients in the conversion
      group was small, the majority of these patients received right-sided nephrectomy.
      CONCLUSIONS: Laparoscopic nephrectomy for the treatment of xanthogranulomatous
      pyelonephritis is feasible and associated with low levels of morbidity. Factors
      including the time required to control the renal vessels, renal length and right
      sided nephrectomy were associated with higher chances of conversion into an open
      procedure.

PMID- 22948459
TI  - Serum testosterone, sex hormone-binding globulin and total calcium levels predict
      the calcaneal speed of sound in men.
AB  - OBJECTIVES: Variations in sex hormones and the calcium balance can influence bone
      health in men. The present study aimed to examine the relationship between the
      calcaneal speed of sound and biochemical determinants of bone mass, such as sex
      hormones, parathyroid hormones and serum calcium. METHODS: Data from 549 subjects
      from the Malaysian Aging Male Study, which included Malay and Chinese men aged 20
      years and older residing in the Klang Valley, were used for analysis. The
      subjects' calcaneal speed of sound was measured, and their blood was collected
      for biochemical analysis. Two sets of multiple regression models were generated
      for the total/bioavailable testosterone and estradiol to avoid multicollinearity.
      RESULTS: The multiple regression results revealed that bioavailable testosterone
      and serum total calcium were significant predictors of the calcaneal speed of
      sound in the adjusted model. After adjustment for ethnicity and body mass index,
      only bioavailable testosterone remained significant; the total serum calcium was
      marginally insignificant. In a separate model, the total testosterone and sex
      hormone-binding globulin were significant predictors, whereas the total serum
      calcium was marginally insignificant. After adjustment for ethnicity and body
      mass index (BMI), the significance persisted for total testosterone and SHBG.
      After further adjustment for age, none of the serum biochemical determinants was
      a significant predictor of the calcaneal speed of sound. CONCLUSION: There is a
      significant age-dependent relationship between the calcaneal speed of sound and
      total testosterone, bioavailable testosterone and sex hormone-binding globulin in
      Chinese and Malay men in Malaysia. The relationship between total serum calcium
      and calcaneal speed of sound is ethnicity-dependent.

PMID- 22948460
TI  - A clinical follow-up of 35 Brazilian patients with Prader-Willi syndrome.
AB  - OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that
      is typically caused by either a paternal microdeletion of a region in chromosome
      15 (microdeletions) or a maternal uniparental disomy of this chromosome. The
      purpose of this study was to describe the most significant clinical features of
      35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to
      determine the effects of growth hormone treatment on clinical outcomes. METHODS:
      A retrospective study was performed based on the medical records of a cohort of
      35 patients diagnosed with Prader-Willi syndrome. The main clinical
      characteristics were compared between the group of patients presenting with
      microdeletions and the group presenting with maternal uniparental disomy of
      chromosome 15. Curves for height/length, weight and body mass index were
      constructed and compared between Prader-Willi syndrome patients treated with and
      without growth hormone to determine how growth hormone treatment affected body
      composition. The curves for these patient groups were also compared with curves
      for the normal population. RESULTS: No significant differences were identified
      between patients with microdeletions and patients with maternal uniparental
      disomy for any of the clinical parameters measured. Growth hormone treatment
      considerably improved the control of weight gain and body mass index for female
      patients but had no effect on either parameter in male patients. Growth hormone
      treatment did not affect height/length in either gender. CONCLUSION: The
      prevalence rates of several clinical features in this study are in agreement with
      the rates reported in the literature. Additionally, we found modest benefits of
      growth hormone treatment but failed to demonstrate differences between patients
      with microdeletions and those with maternal uniparental disomy. The control of
      weight gain in patients with Prader-Willi syndrome is complex and does not depend
      exclusively on growth hormone treatment.

PMID- 22948461
TI  - Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage
      in hamster cheek pouch microcirculation.
AB  - OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from
      injury by preserving microcirculation. This study evaluated vascular permeability
      in a hamster cheek pouch preparation using either short ischemic periods or
      bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion.
      METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of
      different ischemic frequencies and durations (one, three or five shorts periods
      of ischemia, separated by one or five minutes) with 10 min intervals between the
      ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min
      ischemic periods with 10 min intervals between them followed by the topical
      application of histamine (2 uM); bradykinin (400 nM) followed by 30 min of
      ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or
      histamine or bradykinin by themselves). Macromolecular permeability was assessed
      by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg
      body weight), and the number of leaks/cm2 was counted using an intravital
      microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage
      (number of leaks/cm2) was significantly reduced by preconditioning with three and
      five 1 min ischemic periods, one and three 5 min ischemic periods and by
      bradykinin. Histamine-induced macromolecular permeability was also reduced after
      three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and
      bradykinin can function as preconditioning stimuli of the ischemia/reperfusion
      response in the hamster cheek pouch microcirculation. Short ischemic periods also
      reduced histamineinduced macromolecular permeability.

PMID- 22948462
TI  - Vitreous pharmacokinetics and electroretinographic findings after intravitreal
      injection of acyclovir in rabbits.
AB  - OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral
      retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment
      of choice; however, the progression of retinal lesions ceases approximately 2
      days after treatment initiation. An intravitreal injection of acyclovir may be
      used an adjuvant therapy during the first 2 days of treatment when systemically
      administered acyclovir has not reached therapeutic levels in the retina. The aims
      of this study were to determine the pharmacokinetic profile of acyclovir in the
      rabbit vitreous after intravitreal injection and the functional effects of
      acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford
      Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye
      vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was
      injected into the left eye as a control. The animals were sacrificed after 2, 9,
      14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half
      life of acyclovir was determined using high-performance liquid chromatography.
      Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals
      that were sacrificed 28 days after injection according to a modified protocol of
      the International Society for Clinical Electrophysiology of Vision. RESULTS:
      Acyclovir rapidly decayed in the vitreous within the first two days after
      treatment and remained at low levels from day 9 onward. The eyes that were
      injected with acyclovir did not present any electroretinographic changes compared
      with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short,
      and the electrophysiological findings suggest that the intravitreal delivery of 1
      mg acyclovir is safe and well tolerated by the rabbit retina.

PMID- 22948463
TI  - Upregulation of matrix synthesis in chondrocyte-seeded agarose following
      sustained bi-axial cyclic loading.
AB  - OBJECTIVES: The promotion of extracellular matrix synthesis by chondrocytes is a
      requisite part of an effective cartilage tissue engineering strategy. The aim of
      this in vitro study was to determine the effect of bi-axial cyclic mechanical
      loading on cell proliferation and the synthesis of glycosaminoglycans by
      chondrocytes in three-dimensional cultures. METHOD: A strain comprising 10%
      direct compression and 1% compressive shear was applied to bovine chondrocytes
      seeded in an agarose gel during two 12-hour conditioning periods separated by a
      12-hour resting period. RESULTS: The bi-axial-loaded chondrocytes demonstrated a
      significant increase in glycosaminoglycan synthesis compared with samples exposed
      to uni-axial or no loading over the same period (p<0.05). The use of a free
      swelling recovery period prior to the loading regime resulted in additional
      glycosaminoglycan production and a significant increase in DNA content (p<0.05),
      indicating cell proliferation. CONCLUSIONS: These results demonstrate that the
      use of a bi-axial loading regime results in increased matrix production compared
      with uni-axial loading.

PMID- 22948465
TI  - Auditory stimulation and cardiac autonomic regulation.
AB  - Previous studies have already demonstrated that auditory stimulation with music
      influences the cardiovascular system. In this study, we described the
      relationship between musical auditory stimulation and heart rate variability.
      Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases
      using the following keywords: "auditory stimulation", "autonomic nervous system",
      "music" and "heart rate variability". The selected studies indicated that there
      is a strong correlation between noise intensity and vagal-sympathetic balance.
      Additionally, it was reported that music therapy improved heart rate variability
      in anthracycline-treated breast cancer patients. It was hypothesized that
      dopamine release in the striatal system induced by pleasurable songs is involved
      in cardiac autonomic regulation. Musical auditory stimulation influences heart
      rate variability through a neural mechanism that is not well understood. Further
      studies are necessary to develop new therapies to treat cardiovascular disorders.

PMID- 22948464
TI  - Thyroid nodule management: clinical, ultrasound and cytopathological parameters
      for predicting malignancy.
AB  - Although fine-needle aspiration cytology is considered to be the reference method
      for evaluating thyroid nodules, the results are inaccurate in approximately 10
      30% of cases. Several studies have attempted to predict the risk of malignancy in
      thyroid nodules based on age, nodularity, thyrotropin values, thyroid autoimmune
      disease, hot/cold nodule status, and ultrasound parameters. However, no consensus
      has been found, and none of these parameters has significantly affected patient
      management. The management of indeterminate thyroid nodules and re-biopsies of
      nodules with initially benign cytological results remain important and
      controversial topics of discussion. The Bethesda cytological system and several
      studies on the use of molecular markers to predict malignancy from cytological
      samples of thyroid nodules need further clarification. More in-depth discussions
      among and continuous education of the specialists involved in treating thyroid
      disease are necessary to improve the management of these patients. This review
      aims to examine the clinical, laboratory, ultrasound, and scintigraphic
      parameters that can be used for thyroid nodule management.

PMID- 22948466
TI  - Correlation of disability and pain with postural balance among women with chronic
      low back pain.

PMID- 22948467
TI  - Malignant peripheral nerve sheath tumors: clinicopathological aspects, expression
      of p53 and survival.

PMID- 22948468
TI  - The long-term impact of a program to prevent central line-associated bloodstream
      infections in a surgical intensive care unit.

PMID- 22948469
TI  - An innovative model of autologous anorectal transplantation with pudendal nerve
      reconstruction.

PMID- 22948470
TI  - Diagnosis of an ectopic adrenocorticotropic hormonesecreting bronchial carcinoid
      by somatostatin receptor scintigraphy.

PMID- 22948471
TI  - A possible case of Churg-Strauss syndrome in a 9-year-old child.

PMID- 22948472
TI  - MSX2 copy number increase and craniosynostosis: copy number variation detected by
      array comparative genomic hybridization.

PMID- 22948473
TI  - [Genome-wide molecular screening for the identification of new targets in human
      hepatocellular carcinoma].
AB  - Molecular hepatocarcinogenesis represents a step-wise process which in most cases
      is associated with a well-defined chronic liver disease. By meta-analysis of
      classical comparative genomic hybridization (CGH) data an oncogenetic progression
      model could be generated (1q gain-> 8q gain -> 4q loss -> 16q loss -> 13q loss).
      Array-based CGH allows the identification of etiology-dependent and independent
      genomic alterations. The Mouse Double Minute homologue 4 (MDM4) was shown to act
      as an oncogene of 1q32.1 gains in human hepatocellular carcinoma (HCC).
      Integration of genomic and epigenomic data facilitated the identification of
      tumor suppressor gene candidates in human HCC. For instance, Polo-like kinase 3
      (PLK3) is frequently inactivated via promoter hypermethylation in combination
      with a loss of the second allele at 1p34.1. Both MDM4 overexpression and
      methylation-dependent inactivation of PLK3 represent potential targets for future
      therapeutic approaches.

PMID- 22948474
TI  - Performance evaluation of electro-optic effect based graphene transistors.
AB  - Despite the advantages afforded by the unique electronic properties of graphene,
      the absence of a bandgap has limited its applicability in logic devices. This has
      led to a study on electro-optic behavior in graphene for novel device operations,
      beyond the conventional field effect, to meet the requirements of ultra-low power
      and high-speed logic transistors. Recently, two potential designs have been
      proposed to leverage on this effect and open a virtual bandgap for ballistic
      transport in the graphene channel. The first one implements a barrier in the
      centre of the channel, whereas the second incorporates a tilted gate junction. In
      this paper, we computationally evaluate the relative device performance of these
      two designs, in terms of subthreshold slope (SS) and I(ON)/I(OFF) ratio under
      different temperature and voltage bias, for a defect-free graphene channel. Our
      calculations employ pure optical modeling for low field electron transport under
      the constraints of device anatomy. The calculated results show that the two
      designs are functionally similar and are able to provide SS smaller than 60 mV
      per decade. Both designs show similar device performance but marginally top one
      another under different operating constraints. Our results could serve as a guide
      to circuit designers in selecting an appropriate design as per their system
      specifications and requirements.

PMID- 22948475
TI  - Auditory nerve frequency tuning measured with forward-masked compound action
      potentials.
AB  - Frequency selectivity is a fundamental cochlear property. Recent studies using
      otoacoustic emissions and psychophysical forward masking suggest that frequency
      selectivity is sharper in human than in common laboratory species. This has been
      disputed based on reports using compound action potentials (CAPs), which reflect
      activity in the auditory nerve and can be measured in humans. Comparative data of
      CAPs, obtained with a variety of simultaneous masking protocols, have been
      interpreted to indicate similarity of frequency tuning across mammals and even
      birds. Unfortunately, there are several issues with the available CAP
      measurements which hamper a straightforward comparison across species. We
      investigate sharpness of CAP tuning in cat and chinchilla using a forward masking
      notched-noise paradigm--which is less confounded by cochlear nonlinearities than
      simultaneous masking paradigms and similar to what was used in the psychophysical
      study reporting sharper tuning in humans. Our parametric study, using different
      probe frequencies and notch widths, shows relationships consistent with those of
      auditory nerve fibers (ANFs). The sharpness of tuning, quantified by Q(10)
      factors, is negatively correlated with probe level and increases with probe
      frequency, but the Q(10) values are generally lower than the average trend for
      ANFs. Like the single fiber data, tuning for CAPs is sharper in cat than in
      chinchilla, but the two species are similar in the dependence of tuning on probe
      frequency and in the relationship between tuning in ANFs and CAP. Growth-of
      maskability functions show slopes <1 indicating that with increasing probe level
      the probe is more susceptible to cochlear compression than the masker. The
      results support the use of forward-masked CAPs as an alternative measure to
      estimate ANF tuning and to compare frequency tuning across species.

PMID- 22948476
TI  - A 32-year-old male with recurrent hypothermia and hypotension of unknown cause.
AB  - OBJECTIVE: To report a rare case with hypothermia, hypotension and
      thrombocytopenia. CLINICAL PRESENTATION AND INTERVENTION: A 32-year-old male
      presented with recurrent hypothermia, hypotension and thrombocytopenia. He had
      reduced sensitivity to the environmental temperature, but had no structural brain
      abnormalities on MRI. The patient recovered completely with warming and
      supportive treatments. CONCLUSION: This case showed that rare cases of idiopathic
      hypothermia, hypotension and thrombocytopenia should be managed clinically and
      warming and supportive treatments were successful.

PMID- 22948477
TI  - Association of acute myocardial infarction with sudden sensorineural hearing
      loss: a population-based case-control study.
AB  - OBJECTIVE: Although the etiology of sudden sensorineural hearing loss (SSNHL)
      remains unknown, there is increasing evidence suggesting an underlying
      cardiovascular pathomechanism. This study set out to explore a possible
      association between acute myocardial infarction (AMI) and having previously been
      diagnosed with SSNHL by using a population-based dataset with a case-control
      design. METHODS: In this study, we utilized administrative claims data from the
      Taiwan National Health Insurance program to identify 48,674 cases with AMI and to
      randomly select 243,370 controls. Conditional logistic regression was used to
      explore the association between AMI and having previously been diagnosed with
      SSNHL. RESULTS: Of the sampled patients, 1,313 (0.4%) had been diagnosed with
      SSNHL within 5 years before the index date; 340 (0.75% of the cases) were from
      the cases and 974 (0.4% of controls) were from the controls. After adjusting for
      patient geographic region, monthly income, hypertension, diabetes,
      hyperlipidemia, and coronary heart disease, conditional logistic regression
      analysis (conditioned on sex, age group, urbanization level, and index date)
      revealed that the odds ratio for prior SSNHL in patients with AMI was 1.50 (95%
      CI 1.30-1.70; p < 0.001) that of controls. We found that the adjusted odds ratio
      of prior hospitalization for the treatment of SSNHL for cases was 2.11 (95% CI
      1.65-2.69; p < 0.001) times that of controls. CONCLUSIONS: This study identified
      a novel association between AMI and prior SSNHL. The results of this study
      highlight a need for clinicians dealing with SSNHL patients to be alert to their
      risk of subsequent AMI.

PMID- 22948479
TI  - Multifarious beneficial traits and plant growth promoting potential of Serratia
      marcescens KiSII and Enterobacter sp. RNF 267 isolated from the rhizosphere of
      coconut palms (Cocos nucifera L.).
AB  - Two plant growth promoting bacteria designated as KiSII and RNF 267 isolated from
      the rhizosphere of coconut palms were identified as Serratia marcescens and
      Enterobacter sp. based on their phenotypic features, BIOLOG studies and 16S rRNA
      gene sequence analysis. Both bacteria exhibited phosphate solubilization,
      ammonification, and production of indole acetic acid, beta-1, 3 glucanase
      activities and 1-aminocyclopropane-1-carboxylate-deaminase activity. They could
      also tolerate a range of pH conditions, low temperature and salinity (NaCl). In
      addition, S. marcescens KiSII exhibited N- fixation potential, chitinase
      activity, siderophore production and antibiotics production. Seed bacterization
      with these bacteria increased the growth parameters of test plants such as paddy
      and cowpea over uninoculated control in green house assay. In coconut seedlings,
      significant increase in growth and nutrient uptake accompanied with higher
      populations of plant beneficial microorganisms in their rhizospheres were
      recorded on inoculation with both the PGPRs. The present study clearly revealed
      that PGPRs can aid in production of healthy and vigorous seedlings of coconut
      palm which are hardy perennial crops. They offer a scope to be developed into
      novel PGPR based bioinoculants for production of elite seedlings that can benefit
      the coconut farming community and the coconut based ecology.

PMID- 22948480
TI  - Put the student in charge: take part in the biggest revolution ever in teaching
      and learning in dermatology.

PMID- 22948481
TI  - The impact of rotigotine on cardiovascular autonomic function in early
      Parkinson's disease.
AB  - Dysautonomia can occur in early stages of Parkinson's disease (PD) influencing
      tolerance to dopaminergic therapies. Rotigotine, a non-ergot dopamine agonist,
      has recently been developed as an effective alternative antiparkinsonian drug,
      but its influence on the autonomic nervous system was not investigated. Twenty
      subjects out of 34 consecutive de novo PD patients were submitted to full
      assessment of cardiovascular autonomic function before and after reaching a
      stable rotigotine regimen [6 mg/24 h (n = 3) or 8 mg/24 h (n = 17)]. Patients
      reached significant clinical improvement (-27% on the Unified Parkinson's Disease
      Rating Scale part III) and did not show significant differences in cardiovascular
      tests compared to baseline data. However, an unexpected trend towards increasing
      systolic blood pressure after head-up tilt test was detected. Our study
      demonstrates that rotigotine does not influence cardiovascular autonomic
      responses in early de novo PD patients. Consequently, it may represent a well
      tolerated and efficacious therapeutic option in newly diagnosed PD subjects.

PMID- 22948482
TI  - Relationship between neurocognition and regional brain volumes in traumatized
      adolescents with and without posttraumatic stress disorder.
AB  - OBJECTIVES: Studies using convergent neurocognitive and structural imaging
      paradigms in adolescent posttraumatic stress disorder (PTSD) are limited; in the
      current study we used both voxel-based morphometry (VBM) to obtain between-group
      volumetric differences, and Freesurfer to examine the relationship between
      cognition and regional brain volumes. METHODS: Participants were 21 traumatized
      adolescents with PTSD matched with 32 traumatized adolescents without PTSD.
      Magnetic resonance images were obtained on a 1.5-Tesla MAGNETOM Siemens Symphony
      scanner. VBM implemented on FSL was then used to compare between-group grey
      matter volumes, after which Freesurfer was used to obtain global volume and
      thickness measurements in different brain regions. RESULTS: Significant between
      group neurocognitive differences were found for tests of attention, delayed
      recall and visual reconstruction. On VBM, reduced grey matter was found in three
      regions in the PTSD group: left insula, right precuneus and right cingulate
      gyrus, using uncorrected values (p < 0.001), while no statistically significant
      between-group differences were found on the initial Freesurfer stream. Further
      Freesurfer analysis on Qdec revealed significant reductions in the insula for the
      PTSD group. In addition, volumetric changes in the corpus callosum and insula
      were significantly associated with deficits in logical memory and visual
      reproduction on Freesurfer analysis. CONCLUSIONS: Trauma exposure of itself may
      be sufficient to cause structural changes in adolescents regardless of PTSD
      development.

PMID- 22948483
TI  - Development and psychometric testing of the Hemophilia Well-being Index.
AB  - BACKGROUND: Hemophilia experts have recommended that screening tools should be
      introduced into clinical practice to assess patients' needs and perceptions.
      PURPOSE: The present work aims to describe the development of a brief instrument
      for the assessment of subjective well-being of men with hemophilia within an
      international study involving participants from 10 countries. METHODS: Several
      steps were implemented toward achieving this objective: (1) literature review;
      (2) semistructured interviews in different Ibero-American countries; (3)
      exploratory qualitative content analysis of the interviews; (4) definition of the
      construct being evaluated; (5) generation of preliminary items; (6) interjudgment
      ratings of the items, by both patients and experts, to assess comprehension and
      review items; and (7) psychometric testing of an international sample of 342
      patients with hemophilia. RESULTS: Exploratory qualitative study allowed the
      development of an initial pool of items which address salient life domains
      related to well-being. Interjudgment ratings led to improvements in the wording
      and comprehensibilty of the preliminary pool of questions. Psychometric testing
      allowed items to be reviewed according to empirical criteria. The assessment of
      the underlying structure of the questionnaire by exploratory factor analysis
      (generalized least squares) showed a unidimensional model explaining 59.7 % of
      variance. Adequate internal consistency (0.91) and test-retest reliability (0.82)
      were observed for the instrument. Associations with other outcome measures and
      clinical indicators also provided a range of evidence for the instrument's
      validity. CONCLUSIONS: This study presents a new disease-specific tool which is
      able to assess subjective well-being in hemophilia patients.The instrument is
      available in Spanish, Portuguese (Brazilian), and English language versions for
      use in future research.

PMID- 22948486
TI  - Field stitching in thermal probe lithography by means of surface roughness
      correlation.
AB  - A novel stitching method is presented which does not require special purpose
      alignment markers and which is particularly adapted to probe lithographic
      methods, enabling the writing of large patterns exceeding the size limitations
      imposed by high precision scan stages. The technique exploits the natural
      roughness of polymeric resist surfaces as a fingerprint marker for the sample
      position. Theoretical and experimental evidence is provided that sub-nanometer
      metrological accuracy can be achieved by inspecting the surface roughness in
      areas with 1 MUm linear dimensions. The method has been put to the test in a
      thermal probe lithography experiment by writing a composite pattern consisting of
      five 10 MUm * 10 MUm fields which are seamlessly joined together. The observed
      stitching error of 10 nm between fields is dominated by inaccuracies of the
      scanning hardware used in the experiment and is not fundamentally limited by the
      method per se.

PMID- 22948484
TI  - Mitochondrial dysfunction in heart failure.
AB  - Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is
      considered to be a key contributor to the development of both cardiac and
      skeletal myopathy. In HF, several components of cardiac and skeletal muscle
      bioenergetics are altered, such as oxygen availability, substrate oxidation,
      mitochondrial ATP production, and ATP transfer to the contractile apparatus via
      the creatine kinase shuttle. This review focuses on alterations in mitochondrial
      biogenesis and respirasome organization, substrate oxidation coupled with ATP
      synthesis in the context of their contribution to the chronic energy deficit, and
      mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that
      HF is associated with decreased mitochondrial biogenesis and function in both
      heart and skeletal muscle, supporting the concept of a systemic mitochondrial
      cytopathy. The sites of mitochondrial defects are located within the electron
      transport and phosphorylation apparatus and differ with the etiology and
      progression of HF in the two mitochondrial populations (subsarcolemmal and
      interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic
      stimulation, the renin-angiotensin system, and cytokines are evaluated as factors
      responsible for the systemic energy deficit. We propose a cyclic AMP-mediated
      mechanism by which increased adrenergic stimulation contributes to the
      mitochondrial dysfunction.

PMID- 22948485
TI  - Iron deficiency anemia in heart failure.
AB  - Anemia and iron deficiency are quite prevalent in patients with heart failure
      (HF) and may overlap. Both anemia and iron deficiency are associated with worse
      symptoms and adverse clinical outcomes. In the past few years, there has been an
      enormous interest in the subject of iron deficiency and its management in
      patients with HF. In this review, the etiology and relevance of iron deficiency,
      iron metabolism in the setting of HF, studies on iron supplementation in patients
      with HF and potential cardiovascular effects of subclinical iron overload are
      discussed.

PMID- 22948487
TI  - The role of peroral video cholangioscopy in patients with IgG4-related sclerosing
      cholangitis.
AB  - BACKGROUND: The cholangioscopic features of IgG4-related sclerosing cholangitis
      (IgG4-SC) remain undefined. The aim of this study was to clarify these endoscopic
      features using peroral video cholangioscopy (PVCS) in IgG4-SC patients. METHODS:
      PVCS was performed in 33 patients: IgG4-SC (n = 13); primary sclerosing
      cholangitis (PSC; n = 5); and cholangiocarcinoma (n = 15), which included hilar
      cholangiocarcinoma (HCCA; n = 5) and distal cholangiocarcinoma (DCCA; n = 10).
      RESULTS: The most frequent findings on PVCS in the IgG4-SC patients were dilated
      (62 %) and tortuous (69 %) vessels, and absence of partially enlarged vessels.
      The incidence of dilated and tortuous vessels was significantly higher in IgG4-SC
      patients than in PSC patients (p = 0.015). Scarring and pseudodiverticula were
      found significantly more often in PSC patients than in IgG4-SC patients (p =
      0.001 and p = 0.0007, respectively). The incidence of partially enlarged vessels
      was significantly higher in DCCA patients than in IgG4-SC patients (p = 0.004).
      In contrast, the incidence of dilated vessels was significantly higher in IgG4-SC
      patients than in HCCA patients (p = 0.015). PVCS performed after corticosteroid
      therapy showed resolution of bile duct stenosis and dilated, tortuous, or
      partially enlarged vessels, as well as resolution of friability in all patients
      with IgG4-SC. CONCLUSION: Cholangioscopy was useful in differentiating IgG4-SC
      from PSC. In addition, monitoring the patterns of proliferative vessels on PVCS
      may be useful to differentiate IgG4-SC from cholangiocarcinoma.

PMID- 22948488
TI  - EuroFlow: Resetting leukemia and lymphoma immunophenotyping. Basis for companion
      diagnostics and personalized medicine.

PMID- 22948489
TI  - Flow cytometric immunobead assay for fast and easy detection of PML-RARA fusion
      proteins for the diagnosis of acute promyelocytic leukemia.
AB  - The PML-RARA fusion protein is found in approximately 97% of patients with acute
      promyelocytic leukemia (APL). APL can be associated with life-threatening
      bleeding complications when undiagnosed and not treated expeditiously. The PML
      RARA fusion protein arrests maturation of myeloid cells at the promyelocytic
      stage, leading to the accumulation of neoplastic promyelocytes. Complete
      remission can be obtained by treatment with all-trans-retinoic acid (ATRA) in
      combination with chemotherapy. Diagnosis of APL is based on the detection of
      t(15;17) by karyotyping, fluorescence in situ hybridization or PCR. These
      techniques are laborious and demand specialized laboratories. We developed a fast
      (performed within 4-5 h) and sensitive (detection of at least 10% malignant cells
      in normal background) flow cytometric immunobead assay for the detection of PML
      RARA fusion proteins in cell lysates using a bead-bound anti-RARA capture
      antibody and a phycoerythrin-conjugated anti-PML detection antibody. Testing of
      163 newly diagnosed patients (including 46 APL cases) with the PML-RARA
      immunobead assay showed full concordance with the PML-RARA PCR results. As the
      applied antibodies recognize outer domains of the fusion protein, the assay
      appeared to work independently of the PML gene break point region. Importantly,
      the assay can be used in parallel with routine immunophenotyping for fast and
      easy diagnosis of APL.

PMID- 22948490
TI  - EuroFlow standardization of flow cytometer instrument settings and
      immunophenotyping protocols.
AB  - The EU-supported EuroFlow Consortium aimed at innovation and standardization of
      immunophenotyping for diagnosis and classification of hematological malignancies
      by introducing 8-color flow cytometry with fully standardized laboratory
      procedures and antibody panels in order to achieve maximally comparable results
      among different laboratories. This required the selection of optimal combinations
      of compatible fluorochromes and the design and evaluation of adequate standard
      operating procedures (SOPs) for instrument setup, fluorescence compensation and
      sample preparation. Additionally, we developed software tools for the evaluation
      of individual antibody reagents and antibody panels. Each section describes what
      has been evaluated experimentally versus adopted based on existing data and
      experience. Multicentric evaluation demonstrated high levels of reproducibility
      based on strict implementation of the EuroFlow SOPs and antibody panels. Overall,
      the 6 years of extensive collaborative experiments and the analysis of hundreds
      of cell samples of patients and healthy controls in the EuroFlow centers have
      provided for the first time laboratory protocols and software tools for fully
      standardized 8-color flow cytometric immunophenotyping of normal and malignant
      leukocytes in bone marrow and blood; this has yielded highly comparable data
      sets, which can be integrated in a single database.

PMID- 22948492
TI  - Improving accuracy of pressure ulcer staging and documentation using a
      computerized clinical decision support system.
AB  - PURPOSE: The purpose of this study was to evaluate an algorithm designed to
      assess and document pressure ulcers (PUs) via a computerized clinical decision
      support (CCDS) system. SUBJECTS AND SETTING: This study was conducted at Ochsner
      Medical Center, a 500-bed regional referral hospital. Thirty-one nurses,
      including RNs, LPNs, and student nurses, volunteered to participate in the study.
      METHODS: The purpose of this descriptive study was to evaluate CCDS, a new tool
      for PU documentation, in a computer classroom setting. The CCDS program was built
      as an algorithm based on National Pressure Ulcer Advisory Panel's definitions.
      The CCDS incorporates descriptions in drop-down menus with required selections in
      depth, color, and characteristics of the PU by the nurse. The computer program
      then assigns a PU stage. Each participant used the decision support program to
      document the characteristics of 5 PUs presented in photographs and determine the
      stage. Data were analyzed to determine the accuracy of nurses' staging compared
      to that of the researcher and to test for differences between PU groups (overall
      accuracy, accuracy in accepting CCDS suggestion, and accuracy when override
      function used). RESULTS: The results indicate that nurses overall accurately
      staged PUs 64% of the time when using the CCDS program. However, nurses were
      significantly more accurate in staging suspected deep tissue injury and stage I
      PUs when they accepted the CCDS staging versus overriding the suggested stage (P
      < .01). Bivariate analysis did not identify any association between nurses'
      characteristics and accuracy in PU staging for suspected deep tissue injury,
      unstageable ulcers, and stages I and III (P > .05). CONCLUSION: Study findings
      suggest that the use of the CCDS may improve nurses' ability to stage PUs
      accurately. The correct staging of a PU is imperative in nursing's documentation
      and subsequent choice of best practices for improved outcomes.

PMID- 22948491
TI  - The diabetic pregnancy and offspring blood pressure in childhood: a systematic
      review and meta-analysis.
AB  - AIMS/HYPOTHESIS: Offspring of diabetic mothers have increased risk of the
      metabolic syndrome in adulthood. Studies examining BP in offspring of diabetic
      mothers have conflicting conclusions. We performed a systematic review and meta
      analysis of studies reporting offspring BP in children born to diabetic mothers.
      METHODS: Citations were identified in PubMed. Authors were contacted for
      additional data. Systolic and diastolic BP in offspring of diabetic mothers and
      controls were compared. Subgroup analysis of type of maternal diabetes and
      offspring sex were performed. Fixed-effects models were used, and random-effects
      models where significant heterogeneity was present. Meta-regression was used to
      test the relationship between offspring systolic BP and prepregnancy BMI.
      RESULTS: Fifteen studies were included in the review and 13 in the meta-analysis.
      Systolic BP was higher in offspring of diabetic mothers (mean difference 1.88
      mmHg [95% CI 0.47, 3.28]; p = 0.009). Offspring of mothers with gestational
      diabetes had similar diastolic BP to controls, but higher systolic BP (1.39 mmHg
      [95% CI 0.00, 2.77]; p = 0.05); results for type 1 diabetes were inconclusive and
      there were no separate data available on offspring of type 2 diabetic mothers.
      Male offspring of diabetic mothers had higher systolic BP (2.01 mmHg [95% CI
      0.93, 3.10]; p = 0.0003) and diastolic BP (1.12 mmHg [95% CI 0.36, 1.88]; p =
      0.004) than controls; in female offspring there was no difference (systolic: 0.54
      mmHg [95% CI -1.83, 2.90], p = 0.66; diastolic: 0.51 mmHg [95% CI -1.07, 2.09], p
      = 0.52). The correlation between offspring systolic BP and maternal prepregnancy
      BMI was not significant (p = 0.37). CONCLUSIONS/INTERPRETATION: Offspring of
      diabetic mothers have higher systolic BP than controls. Differences related to
      sex and type of maternal diabetes require further investigation.

PMID- 22948493
TI  - Constipation in community-dwelling elders: prevalence and associated factors.
AB  - PURPOSE: The purpose of this study was to measure the prevalence of constipation
      in community-dwelling elders and to analyze associated factors. SUBJECTS AND
      SETTING: The study sample comprised 186 elders from 5 Senior Citizen Centers in
      Jeju-si. DESIGN: This community-based cross-sectional study used a structured
      questionnaire to collect data via interviews with respondents. METHODS:
      Interviews were completed by the principal investigator and an assistant.
      Interviews required approximately 20 minutes and were completed in the senior
      centers. Respondents were queried about demographic characteristics, body mass
      index, alcohol consumption, level of exercise, depression, and lower urinary
      tract symptoms including urinary incontinence. Bowel elimination symptoms were
      queried, and the presence of constipation was established using Rome II criteria.
      Multiple logistic regression analysis was used to test for associations between
      potential risk factors and constipation. RESULTS: The prevalence of constipation
      in this community-dwelling sample population was 25.8%. The most common symptoms
      were "hard or lumpy stools" reported by 30.8% and "straining during a bowel
      movement" reported by 27.1%. Analysis via logistic regression found that
      constipation is associated with lower urinary tract symptoms (odds ratio = 1.1;
      95% confidence interval: 1.03-1.14) and obesity (body mass index >= 25 kg/m)
      (odds ratio = 2.4; 95% confidence interval: 1.01-5.57). CONCLUSIONS: Slightly
      more than one quarter of the elderly reported symptoms of constipation.
      Associated factors were presence of lower urinary tract symptoms and obesity.

PMID- 22948494
TI  - Methods of bowel management in critical care: a randomized controlled trial.
AB  - PURPOSE: The purpose of this study was to compare 3 methods of bowel management
      to control fecal incontinence in adult critical care patients and their effect on
      incontinence-associated dermatitis, pressure ulcer prevalence, and clinician
      satisfaction. SUBJECTS AND SETTING: Fifty-nine adult patients in critical care
      with liquid fecal incontinence were recruited from 6 critical care units in a
      large Midwest healthcare system. METHODS: Subjects were randomly assigned to 1 of
      3 groups: bowel management system catheter, rectal/nasopharyngeal trumpet, or
      usual care. Subjects were assessed daily for incontinence-associated dermatitis,
      pressure ulcer prevalence, and other clinical data. Direct care nurse
      satisfaction with each method was evaluated by self-administered survey. RESULTS:
      Incontinence-associated dermatitis severity and pressure ulcer prevalence did not
      differ across groups at baseline. Over time, the change in incontinence
      associated dermatitis severity score was significantly different across groups (P
      < .001). There were no significant differences in proportion of patients
      experiencing pressure ulcers during the study among groups. Clinicians reported
      significantly greater satisfaction with the bowel management system (P = .007)
      and rectal trumpet (P = .001) as compared to usual care. In addition, economic
      and safety benefits were identified with use of internal fecal devices.
      Specifically, an economic savings of $3100 to $3400 per 29 days of care was
      identified. Subjects experienced no adverse side effects when internal devices
      were used. CONCLUSION: Results of this randomized controlled trial provide new
      information for the care of patients with fecal incontinence in the critical care
      setting. Incontinence-associated dermatitis severity scores differed across
      groups over time, pressure ulcer prevalence did not differ across groups over
      time, use of an internal device or bowel management system improved clinician
      satisfaction, and the use of internal fecal methods was more cost-effective than
      usual care.

PMID- 22948495
TI  - Predictive power of the Braden scale for pressure sore risk in adult critical
      care patients: a comprehensive review.
AB  - Critical care is designed for managing the sickest patients within our healthcare
      system. Multiple factors associated with an increased likelihood of pressure
      ulcer development have been investigated in the critical care population.
      Nevertheless, there is a lack of consensus regarding which of these factors poses
      the greatest risk for pressure ulceration. While the Braden scale for pressure
      sore risk is the most commonly used tool for measuring pressure ulcer risk in the
      United States, research focusing on the cumulative Braden Scale score and
      subscale scores is lacking in the critical care population. This author conducted
      a literature review on pressure ulcer risk assessment in the critical care
      population, to include the predictive value of both the total score and the
      subscale scores. In this review, the subscales sensory perception, mobility,
      moisture, and friction/shear were found to be associated with an increased
      likelihood of pressure ulcer development; in contrast, the Activity and Nutrition
      subscales were not found to predict pressure ulcer development in this
      population. In order to more precisely quantify risk in the critically ill
      population, modification of the Braden scale or development of a critical care
      specific risk assessment tool may be indicated.

PMID- 22948496
TI  - Development of a pressure ulcer trigger tool for the neonatal population.
AB  - A large Midwest level IIIb neonatal intensive care unit located in a 500-bed
      teaching hospital implemented quarterly skin prevalence surveys to monitor
      prevalence of altered skin integrity including pressure ulcers, diaper dermatitis
      (incontinence-associated dermatitis), and skin damage as a result of intravenous
      therapy, adhesive, or medical devices. Pressure ulcer prevalence varied from 0%
      to 1% per quarter, and no pressure ulcer risk assessment tool was regularly
      implemented. Therefore, a working group was formed to identify a risk assessment.
      The Iowa Model for Evidence-Based Practice was used to guide the project. A
      literature review was completed to identify validated instruments, but available
      tools were judged lengthy for routine clinical use. Therefore, we developed a
      short trigger tool comprising 3 questions to identify infants at risk for
      pressure ulcer development.

PMID- 22948497
TI  - Efficacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized,
      double-blind, placebo-controlled trial for cervical dystonia.
AB  - OBJECTIVE: To evaluate the efficacy, tolerability, and neutralizing antibodies in
      the treatment of cervical dystonia with onabotulinumtoxinA (BOTOX). METHODS:
      Subjects received onabotulinumtoxinA (containing original bulk toxin) treatment
      in a 10-week open-label period (period 1). Eligible subjects who completed this
      period were randomized to onabotulinumtoxinA or placebo in a 10-week double-blind
      period (period 2). The primary outcome measures were the Cervical Dystonia
      Severity Scale and the physician Global Assessment Scale at week 6 in period 2.
      Serum samples for immunogenicity tests were taken at baseline and study exit. The
      potential impact of preexisting neutralizing antibodies (nAbs) was examined
      across subgroups for period 1 and by analysis of covariance for period 2.
      RESULTS: Of 214 subjects enrolled in period 1, 170 enrolled in period 2 and
      received placebo (n = 82) or onabotulinumtoxinA (n = 88). In period 1, subjects
      with preexisting nAbs responded similarly to those without preexisting nAbs. In
      period 2, onabotulinumtoxinA produced significantly greater improvements than
      placebo on the Cervical Dystonia Severity Scale (-1.81 vs -0.31 points; P =
      0.012) and physician Global Assessment Scale (61.7% vs. 41.6% improved; P =
      0.022) at the primary time point week 6, using baseline severity and neutralizing
      antibody (nAb) status at study entry as covariates. Two subjects seroconverted
      from nAb negative at baseline to nAb positive at study exit but remained
      responsive to onabotulinumtoxinA during both the open and blinded treatment
      periods. Rhinitis and treatment-related dysphagia were reported significantly
      more frequently with onabotulinumtoxinA than placebo. CONCLUSION:
      OnabotulinumtoxinA was well tolerated and more effective than placebo for the
      treatment of cervical dystonia. Subject nAb status at baseline was not a clear
      predictor of response to onabotulinumtoxinA.

PMID- 22948498
TI  - A simple and practical method that prepares high molecular weight DNA ladders.
AB  - The purpose of the current study was to report a simple and practical method to
      prepare high molecular weight (mw) DNA ladders. The method involves 1,000-4,000
      base pairs (bp) DNA fragments being amplified by polymerase chain reaction (PCR),
      using lambda DNA as a template. The constructed plasmids are digested by
      restriction endonucleases to produce 5-, 6-, 8- and 10-kb DNA fragments, followed
      by purification and precipitation with ethanol, and mixed proportionally. The
      1,000-4,000-bp DNA fragments were successfully generated by PCR and 5-, 6-, 8-
      and 10-kb DNA fragments were obtained through the digestion of the plasmids. The
      bands of the prepared high mw DNA ladder were clear and may aid future molecular
      biology studies.

PMID- 22948500
TI  - [Alert on paternal postpartum depression].

PMID- 22948499
TI  - Potassium supply and homeostasis in the osmotolerant non-conventional yeasts
      Zygosaccharomyces rouxii differ from Saccharomyces cerevisiae.
AB  - Three different transport systems exist to accumulate a sufficient amount of
      potassium cations in yeasts. The most common of these are Trk-type transporters,
      which are used by all yeast species. Though most yeast species employ two
      different types of transporters, we only identified one gene encoding a potassium
      uptake system (Trk-type) in the genome of the highly osmotolerant yeast
      Zygosaccharomyces rouxii, and our results showed that ZrTrk1 is its major (and
      probably only) specific potassium uptake system. When expressed in Saccharomyces
      cerevisiae, the product of the ZrTRK1 gene is localized to the plasma membrane
      and its presence efficiently complements the phenotypes of S. cerevisiae trk1?
      trk2? cells. Deletion of the ZrTRK1 gene resulted in Z. rouxii cells being almost
      incapable of growth at low K(+) concentrations and it changed some cell
      physiological parameters in a way that differs from S. cerevisiae. In contrast to
      S. cerevisiae, Z. rouxii cells without the TRK1 gene contained less potassium
      than the control cells and their plasma membrane was significantly hyperpolarized
      compared with those of the parental strain when grown in the presence of 100 mM
      KCl. On the other hand, subsequent potassium starvation led to a substantial
      depolarization which is again different from S. cerevisiae. Plasma-membrane
      hyperpolarization did not prevent the efflux of potassium from Z. rouxii
      trk1Delta cells during potassium starvation, and the activity of ZrPma1 is less
      affected by the absence of ZrTRK1 than in S. cerevisiae. The use of a newly
      constructed Z. rouxii-specific plasmid for the expression of pHluorin showed that
      the intracellular pH of the Z. rouxii wild type and the trk1? mutant is not
      significantly different. Together with the fact that Z. rouxii cells contain a
      significantly lower amount of intracellular potassium than identically grown S.
      cerevisiae cells, our results suggest that this highly osmotolerant yeast species
      maintain its intracellular pH and potassium homeostasis in way(s) partially
      distinct from S. cerevisiae.

PMID- 22948501
TI  - [Alcohol use pattern in pregnant women cared for in a public university hospital
      and associated risk factors].
AB  - PURPOSE: To determine the pattern of alcohol use before and during pregnancy and
      associated risk factors in puerperal women hospitalized in a public university
      hospital in Southeastern Brazil. METHODS: Between June and September 2009, 493
      puerperae were consecutively evaluated. Those with cognitive impairment were
      excluded from the study. The AUDIT and CAGE questionnaires were used to diagnose
      alcohol use/abuse before pregnancy, in addition to the T-ACE during pregnancy.
      Another questionnaire was applied to collect sociodemographic data, such as age,
      educational level, marital status, and household income. The chi2 test was used
      in the statistical analysis and the Odds Ratio (OR) and 95% confidence interval
      (95%CI) were calculated. A p-value <0.05 was considered to be significant.
      RESULTS: Before pregnancy, the CAGE was positive in 50/405 (12.3%) women and the
      AUDIT identified alcohol use in 331 (67.1%), which was of low risk in 233
      (47.3%), risky in 73 (14.8%), and harmful or indicating possible alcohol
      dependence in 25 (5%). During pregnancy, the CAGE was positive in 53/405 (13.1%)
      women and the T-ACE in 84 (17%); the AUDIT identified alcohol use in 114 women,
      which was of low risk in 73 (14.8%), risky in 27 (5.5%), and harmful or
      indicating possible alcohol dependence in 14 (2.8%). During pregnancy, alcohol
      use was more frequent (OR=2.8; 95%CI 1.2 - 6.2) among women with a lower
      educational level (8.8 versus 3.3%) and more frequent (OR=3.8; 95%CI 1.3 - 11.1)
      among those who did not cohabit with a partner (6 versus 1.7%). Among pregnant
      women who drank alcohol, 49/114 (43%) were advised to stop drinking. CONCLUSIONS:
      Alarming alcohol use was observed during pregnancy, especially among pregnant
      women with a lower educational level and those who did not cohabit with a
      partner. There was a low frequency of counseling aimed at abstinence and the
      AUDIT was the instrument that most frequently diagnosed alcohol consumption.

PMID- 22948502
TI  - [Body mass index and gestational weight gain as factors predicting complications
      and pregnancy outcome].
AB  - PURPOSE: To evaluate the impact of body mass index (BMI) at the beginning of
      pregnancy and weight gain on pregnancy outcome so that this measure can be
      implemented and valued by prenatal care health services. METHOD: Cross-sectional
      population-based study of all births in the only two hospitals in Rio Grande city
      (Brazil), in 2007. Among the 2,557 mothers interviewed, it was possible to
      calculate BMI in only 1,117. The Stata 11 software was used for data analysis.
      Logist regression was applied to the outomes involving diabetes mellitus,
      premature labor and cesarean section. Regarding birth weight, data were adjusted
      by multinomial logistic regression using as base category the group of 2,500 to
      4,000 g. The level of significance was set at p-value <0.05 in a two-tailed test.
      RESULTS: There was no increased risk of hypertension or diabetes in patients in
      the different groups of BMI and weight gain. The risk of preterm delivery was
      evident in the group with a weight gain <= 8 kg (p<0.05). Regarding the route of
      delivery, it was observed that the higher the BMI in early pregnancy (p=0.001)
      and the greater the weight gain during pregnancy (p=0.004), the greater the risk
      of surgical delivery, which reached 11% in the group of obese mothers (p=0.004)
      and 12% in the group with a weight gain >= 17 kg (p=0.001). The weight of the
      newborns was influenced by BMI and weight gain, and the higher the BMI in early
      pregnancy and the gestational weight gain, the greater the risk of macrosomia.
      CONCLUSION: The monitoring of BMI and weight gain during pregnancy is a low cost
      and useful procedure for the establishment of nutritional interventions aimed at
      reducing maternal and fetal risks.

PMID- 22948503
TI  - [Nonimmune hydrops fetalis: two decades of experience in a university hospital].
AB  - PURPOSE: To identify the etiology of nonimmune hydrops fetalis cases in pregnant
      women diagnosed and referred for prenatal care. METHODS: Retrospective analysis
      of cases with nonimmune hydrops fetalis that were monitored between March 1992
      and December 2011. Diagnosis was confirmed by the presence of fetal subcutaneous
      edema (>= 5 mm) with effusion in at least one serous cavity using obstetric
      ultrasound, and etiological investigation was conducted with cytogenetic
      (karyotype), infectious (syphilis, parvovirus B19, toxoplasmosis, rubella,
      cytomegalovirus, adenovirus and herpes simplex), hematologic and metabolic
      (inborn errors) analysis and fetal echocardiography. Twin pregnancies were
      excluded. Statistical analysis was performed using the chi2 test for adhesion
      (software R 2.11.1). RESULTS: We included 116 patients with nonimmune hydrops
      fetalis; the etiology was elucidated in 91 cases (78.5%), while 25 cases (21.5%)
      were classified as idiopathic. Most cases had a chromosomal etiology, for a total
      of 26 cases (22.4%), followed by lymphatic etiology with 15 cases (12.9% with 11
      cases of cystic hygroma), and cardiovascular and infectious etiology with 14
      cases each (12.1%). In the remaining cases, the etiology was thoracic in 6.9%
      (eight cases), malformation syndromes in 4.3% (five cases), extrathoracic tumors
      in 3.4% (four cases), metabolic in 1.7% (two cases), and hematologic,
      gastrointestinal and genitourinary in 0.9% (one case each). During the postnatal
      period, 104 cases were followed up until the 40th day of life, and 12 cases had
      intrauterine fetal death. The survival rate of these 104 newborns was 23.1% (24
      survived). CONCLUSION: An attempt should be made to clarify the etiology of
      hydrops diagnosed during pregnancy since the condition is associated with a wide
      spectrum of diseases. It is especially important to determine whether a
      potentially treatable condition is present and to identify disease at risk for
      recurrence in future pregnancies for adequate pre-conception counseling.

PMID- 22948504
TI  - [Analysis of muscle strength and body composition of women with polycystic ovary
      syndrome].
AB  - PURPOSE: To compare the metabolic parameters, body composition and muscle
      strength of women with Polycystic Ovary Syndrome (PCOS) to those of women with
      ovulatory menstrual cycles. METHODS: A case-control study was conducted on 27
      women with PCOS and 28 control women with ovulatory cycles, aged 18 to 27 years
      with a body mass index of 18 to 39.9 kg/m2, who did not practice regular physical
      activity. Serum testosterone, androstenedione, prolactin, sex hormone-binding
      globulin (SHBG), insulin and glycemia levels were determined. Free androgen index
      (FAI) and resistance to insulin (by HOMA) were calculated. The volunteers were
      submitted to evaluation of body composition based on skin folds and DEXA and to 1
      RM maximum muscle strength tests in three exercises after familiarization
      procedures and handgrip isometric force was determined. RESULTS: Testosterone
      levels were higher in the PCOS group than in the Control Group (68.07 +/- 20.18
      versus 58.20 +/- 12.82 ng/dL; p=0.02), as also were the FAI (282.51 +/- 223.86
      versus 127.08 +/- 77.19; p=0.01), insulin (8.41 +/- 7.06 versus 4.05 +/- 2.73
      uIU/mL; p=0.01), and HOMA (2.3 +/- 2.32 versus 1.06 +/- 0.79; p=0.01), and SBHG
      levels were lower (52.51 +/- 43.27 versus 65.45 +/- 27.43 nmol/L; p=0.04). No
      significant differences in body composition were observed between groups using
      the proposed methods. The PCOS group showed greater muscle strength in the 1-RM
      test in the bench press (31.2 +/- 4.75 versus 27.79 +/- 3.63 kg; p=0.02), and leg
      extension exercises (27.9 +/- 6.23 versus 23.47 +/- 4.21 kg; p=0.02) as well as
      handgrip isometric force (5079.61 +/- 1035.77 versus 4477.38 +/- 69.66 kgf/m2,
      p=0.04). PCOS was an independent predictor of increase muscle strength in bench
      press exercises (estimate (E)=2.7) (p=0.04) and leg extension (E=3.5) (p=0.04),
      and BMI in the exercise of isometric handgrip (E=72.2) (p<0.01), bench press
      (E=0.2) (p=0.02) and arm curl (E=0.3) (p<0.01). No association was found between
      HOMA-IR and muscle strength. CONCLUSIONS: Women with POS showed greater muscle
      strength, with no difference in body composition, and IR was not associated with
      muscle strength performance. Muscle strength may be possibly related to high
      levels of androgens in these women.

PMID- 22948505
TI  - [Morphology of the interstitial cells of rat polycystic ovaries: an experimental
      study].
AB  - PURPOSES: To evaluate the histomorphometry of ovarian interstitial cells, as well
      as the blood sex steroid concentrations of female rats with polycystic ovaries
      induced by continuous light. METHODS: Twenty female rats were divided into two
      groups: Control Group - in the estrous phase (CtrlG), and a group of rats with
      polycystic ovaries induced by continuous illumination (POG). CtrlG animals were
      maintained on a light period from 07:00 a.m. to 07:00 p.m., and POG animals with
      continuous illumination (400 Lux) for 60 days. After this period all animals were
      anesthetized and blood was collected for the determination of serum estradiol
      (E2), progesterone (P4), and testosterone (T), followed by removal of the ovaries
      that were fixed in 10% formalin and processed for paraffin embedding. Five-um
      histological sections were stained with hematoxylin and eosin and used for
      histomorphometric analysis. Morphological analyses, cyst count, determination of
      concentration and of the nuclear volume of interstitial cells were performed with
      the aid of a light microscope adapted to a high resolution camera (AxioCam),
      whose images were transmitted to and analyzed by the computer using AxioVision
      Rel 4.8 software (Carl Zeiss). Data were analyzed statistically by the Student's
      t-test (p<0.05). RESULTS: Morphological analysis showed the presence of ovarian
      cysts in POG animals and corpora lutea in CtrlG animals, as well as evidence of
      the origin of interstitial cells from the internal theca of these cysts. POG
      animals presented increased serum estradiol levels (pg/mL) compared to CtrlG
      animals (POG=124.9 +/- 4.2>CtrlG=73.2 +/- 6.5, p<0.05), the same occurring with
      testosterone levels (pg/mL) (POG=116.9 +/- 4.6>CtrlG=80.6 +/- 3.9, p<0.05).
      However, progesterone levels (ng/mL) were higher in CtrlG than in POG animals
      (CtrlG=16.3 +/- 2.0>POG=4.2 +/- 1.5, p<0.05). Morphometry showed a significant
      increase in nuclear volume in POG animals (POG=102.1 +/- 5.2>CtrlG=63.6 +/- 16.5,
      p<0.05), as well as in the area occupied (%) by interstitial cells (POG=24.4 +/-
      6.9>CtrlG=6.9 +/- 3.2, p<0.05) compared to CtrlG animals. CONCLUSION: The
      interstitial cells of the rat polycystic ovary probably originate from ovarian
      cysts due to the degeneration of granulosa cells and differentiation of the
      internal theca cells. The elevations of serum testosterone and estradiol were
      probably due to the significant increase in cell activity and in the area
      occupied by interstitial cells.

PMID- 22948506
TI  - [Influence of menopausal symptoms on sexual function in middle-aged women].
AB  - PURPOSE: To evaluate the influence of climacteric symptoms on the sexual function
      in middle-aged women. METHODS: A cross-sectional population study was conducted
      on a sample of 370 middle-aged women, aged 40 to 65 years-old, cared for at the
      Basic Health Units in Natal, in the state of Rio Grande do Norte, Brazil. We used
      a questionnaire containing questions on sociodemographic, clinical, and
      behavioral characteristics. Sexual function was evaluated by the Female Sexual
      Function Index (FSFI), while the menopause symptoms by the Menopause Rating Scale
      (MRS). RESULTS: In the studied group, 67% of the women reported risk for sexual
      dysfunction (FSFI<=26.5). All FSFI domains (desire, arousal, lubrication, orgasm,
      satisfaction, and pain) were lower in women with risk for sexual dysfunction
      (p<0.001). The arousal, orgasm, and pain domains were most likely to contribute
      to lower FSFI scores. All somatovegetative, urogenital, and psychological MRS
      symptoms were more elevated in women with risk for sexual dysfunction, being
      significant for all comparisons (p<0.001). Logistic regression analysis revealed
      that the likelihood of women with risks of sexual dysfunction to present hot
      flushes, depression, sexual problems, and vaginal dryness was, respectively, 2.1
      (95%CI 1.2 - 3.5); 2.4 (95%CI 1.5 - 4.1); 2.3 (95%CI 1.4 - 3.8), and 2.2 (95%CI
      1.3 - 3.6) times higher, respectively, compared to those without any risk.
      CONCLUSION: Climacteric symptoms seem to influence the sexual function in middle
      aged women.

PMID- 22948507
TI  - Is liver transplantation associated with decreased bone mass in climacteric
      women?
AB  - PURPOSE: To evaluate whether climacteric women undergoing liver transplantation
      had higher prevalence of decreased bone mass than those without any liver
      disease. METHODS: A cross-sectional study with 48 women receiving follow-up care
      at a university hospital in Southeastern Brazil, from February 4th 2009 to
      January 5th 2011, was conducted. Of these women, 24 were 35 years or older and
      had undergone liver transplantation at least one year before study entry. The
      remaining 24 women had no liver disease and their ages and menstrual patterns
      were similar to those of transplanted patients. Laboratorial tests (follicle
      stimulating hormone and estradiol) and bone density measurements of the lumbar
      spine and femur (equipment Hologic, Discovery WI) were performed. Statistical
      analysis was carried out by Fisher's exact test, simple Odds Ratio (OR), and
      multiple logistic regression. RESULTS: Mean age of the women included in the
      study was 52.8 (+/- 10.7) years-old, 27.1% were premenopausal and 72.9% were
      peri/postmenopausal. Approximately 14.6% of these women exhibited osteoporosis
      and 35.4% had low bone mass. The following items were associated with decreased
      bone mass: being postmenopausal (OR=71.4; 95%CI 3.8 - 1,339.7; p<0.0001), current
      age over 49 years-old (OR=11.4; 95%CI 2.9 - 44.0; p=0.0002), and serum estradiol
      levels lower than 44.5 pg/mL (OR=18.3; 95%CI 3.4 - 97.0; p<0.0001). Having a
      history of liver transplantation was not associated with decreased bone mass
      (OR=1.4; 95%CI 0.4 - 4.3; p=0.56). CONCLUSION: Liver transplantation was not
      associated with decreased bone mass in this group of climacteric women.

PMID- 22948509
TI  - IRPA and the IRPA13 Glasgow Congress, May 2012.

PMID- 22948508
TI  - Association of nerve growth factor, chemokine (C-C motif) ligands and
      immunoglobulin E with pruritus in cutaneous T-cell lymphoma.
AB  - Many patients with cutaneous T-cell lymphoma (CTCL) experience severe pruritus.
      This study evaluated serum levels of nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) in patients with CTCL. Although serum NGF and BDNF
      levels in patients with CTCL were not significantly higher than in healthy
      controls, serum NGF levels in patients with Sezary syndrome were higher than in
      those with mycosis fungoides and in healthy controls. Enhanced NGF expression by
      keratinocytes and increased dermal nerve fibres were detected in lesional skin of
      subjects with Sezary syndrome. Correlations between pruritus in CTCL and serum
      levels of NGF, BDNF, chemokine (C-C motif) ligand 1 (CCL1), CCL17, CCL26, CCL27,
      lactate dehydrogenase (LDH), IgE, and soluble interleukin-2 receptor were
      analysed. Serum CCL1, CCL26, LDH, and IgE levels correlated with pruritus in
      patients with CTCL. NGF may be associated with increased dermal nerve fibres and
      pruritus in Sezary syndrome, and CCL1, CCL26, and IgE may be associated with
      pruritus in CTCL.

PMID- 22948510
TI  - The ATP or the natural history of neurotransmission.

PMID- 22948511
TI  - Influence of the quality of endodontic treatment and coronal restorations on the
      prevalence of apical periodontitis in a Turkish Cypriot population.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of periapical
      lesions in root canal-treated teeth in a Turkish Cypriote population and to
      investigate the influence of the quality of root canal fillings and coronal
      restorations on the prevalence of periapical lesions. SUBJECTS AND METHODS: The
      sample for this cross-sectional study consisted of 1,006 adult patients seeking
      routine dental care. Patients who had received dental care in the last 2 years
      were excluded. Radiographs of 2,200 root canal-treated teeth were evaluated. The
      teeth were grouped according to the radiographic quality of the root canal
      filling and the coronal restoration. Periapical status was assessed using
      periapical index (PAI) scores. RESULTS: Of the 2,200 root canal-treated teeth,
      1,364 (62%) had apical periodontitis as compared with 1,364 (5.5%) of the total
      sample. Root-filled teeth classified as adequately treated had apical
      periodontitis in 223 (26.6%) cases compared with 1,192 (87.7%) in teeth
      classified as inadequately root filled. PAI 1 scores of adequate root canal
      treatment were significantly higher than in inadequate root canal treatment,
      regardless of the quality or presence of coronal restorations (p < 0.01).
      CONCLUSION: Our findings showed a high prevalence of periapical pathology with or
      without endodontic treatment and poor technical standard of both root fillings
      and coronal restorations of root-treated teeth. Hence, we suggest the need for
      better education for dental health providers so that they can perform better root
      canal treatments and coronal restorations.

PMID- 22948512
TI  - The determination of extinction coefficient of CuInS2, and ZnCuInS3 multinary
      nanocrystals.
AB  - A pioneering work for determining the extinction coefficient of colloidal
      semiconductor nanocrystals (NCs) has been cited over 1500 times (W. Yu, W. Guo,
      X. G. Peng, Chem. Mater., 2003, 15, 2854-2860), indicating the importance of
      calculating NC concentration for further research and applications. In this
      study, the size-dependent nature of the molar extinction coefficient of "greener"
      CuInS(2) and ZnCuInS(3) NCs with emission covering the whole visible to near
      infrared (NIR) is presented. With the increase of NC size, the resulting
      quantitative values of the extinction coefficients of ternary CuInS(2) and
      quaternary ZnCuInS(3) NCs are found to follow a power function with exponents of
      2.1 and 2.5, respectively. Obviously, a larger value of extinction coefficient is
      observed in quaternary NCs for the same size of particles. The difference of the
      extinction coefficient from both samples is clearly demonstrated due to
      incorporating ZnS with a much larger extinction coefficient into CuInS(2) NCs.

PMID- 22948513
TI  - Evaluating the redistributive impact of public health expenditure using an
      insurance value approach.
AB  - This article analyses the redistributive impact of public health expenditure in
      Spain using an insurance value approach to compute individual and household's
      value of health services non-cash benefit. We model the intensity of use of
      different health care services using a count data framework on a nationally
      representative health care survey and then predict probabilities on the 2006
      Spanish EU-SILC sample. This allows us to extend disposable income with the
      expected monetary value of public health services and to compare it with strictly
      cash income. Since non-cash income due to public health services is associated
      with health needs, we use needs-adjusted equivalence scales to perform
      distributional analysis and poverty/inequality comparisons. The results show that
      public health expenditure in Spain acts progressively on income distribution, and
      that health in-kind benefits, once considered as part of disposable income, can
      be extremely effective in reducing poverty and inequality. 

PMID- 22948515
TI  - PSMC1 Gene in Parkinson's Disease.
AB  - BACKGROUND: Impairment of the ubiquitin-proteasome system has been suggested to
      play an important role in the pathogenesis of Parkinson's disease (PD). The 26S
      proteasome regulatory subunit 1 is encoded by the gene PSMC1 in humans. PSMC1
      knockout mice showed a PD-like phenotype. Our aim was to analyze the association
      between variations in this gene and the susceptibility to develop PD. METHODS: We
      included 283 PD patients (165 males and 118 females) with a mean age of 63.6+/
      11.2 years (mean age at onset 55.4+/-12.7 years), and 316 unrelated control
      subjects (193 males and 123 females) with a mean age of 61.5+/-12.3 years. Four
      polymorphisms, providing haplotype information of PSMC1, were genotyped using
      TaqMan assays. Moreover, in order to identify new variations, all exons of the
      PSMC1 gene and their exon-intron boundaries were analyzed using high-resolution
      melting analysis. RESULTS: Minor allele frequencies in PD patients and control
      subjects were similar. The gene coding sequence analysis showed no variation
      associated with the disease either. CONCLUSIONS: Our results suggest that there
      is no association between variations or haplotypes in the PSMC1 gene and PD,
      indicating that this gene is probably not involved in the pathogenesis of PD.

PMID- 22948514
TI  - Curcumin protects against concanavalin A-induced hepatitis in mice through
      inhibiting the cytoplasmic translocation and expression of high mobility group
      box 1.
AB  - The aims of this study were to examine the anti-inflammatory effect of curcumin
      on concanavalin A (ConA) induced hepatitis in mice, and to elucidate its
      underlying molecular mechanisms. Mice received curcumin by gavage before ConA
      intravenous administration. The results showed that curcumin pretreatment
      attenuated ConA-induced hepatitis. Enzyme linked immunosorbent assay (ELISA)
      results showed that serum levels of high mobility group box 1 (HMGB1) increased
      at 4 h and reached its peak value at 12 h after challenge with ConA; but this
      increase was significantly inhibited by curcumin. Furthermore, curcumin
      significantly decreased the HMGB1 translocation from nucleus to cytoplasm of
      hepatocytes in ConA-induced mice. The levels of HMGB1 mRNA and protein expression
      in the liver were also significantly lowered in curcumin-treated mice. In
      addition, curcumin inhibited intrahepatic expression of tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 protein. In conclusion, the
      results indicated that curcumin protected against ConA-induced hepatitis in mice;
      and the beneficial effects may be partly through inhibition of HMGB1
      translocation in hepatocytes, release into the plasma and expression in livers.

PMID- 22948516
TI  - Antibacterial and antioxidant potency of floral honeys from different botanical
      and geographical origins.
AB  - In order to assess their physicochemical and antioxidant properties as well as
      their antimicrobial potency, four varieties of honey from different botanical and
      geographical origins were used. The agar incorporation method was used to
      determine the antimicrobial potency of honeys. The total phenol content was
      determined by a modified Folin-Ciocalteu method and the free radical scavenging
      activity by the Fe(3+)reducing power (FRAP) assay. Manuka honey was the most
      effective against Staphylococcus aureus Oxa R and S. aureus Oxa S with a Minimum
      Inhibitory Concentration (MIC) of 6% and 7%, respectively, whereas wild carrot
      honey was the most effective against Pseudomonas aeruginosa, with a MIC of 12%.
      Lavender honey was the least effective against all tested strains, even though
      was found to have the lowest pH and water content. Manuka honey had the highest
      content of polyphenols, with 899.09 +/- 11.75 mg gallic acid/kg, whereas lavender
      honey had the lowest, with 111.42 +/- 3.54 mg gallic acid/kg. A very significant
      correlation (r value was 0.9079 at P < 0.05) was observed between the total
      polyphenolic content and the Fe(2+) content formed in the presence of the honey
      antioxidants. The differences between honey samples in terms of antibacterial and
      antioxidant activity could be attributed to the natural variations in floral
      sources of nectar and the different locations.

PMID- 22948517
TI  - Classification of persistent left superior vena cava considering presence and
      development of both superior venae cavae, the anastomotic ramus between superior
      venae cavae, and the azygos venous system.
AB  - Subjects with persistent left superior vena cava were classified on the basis of
      the presence and thickness of both superior venae cavae, the anastomotic ramus
      between the superior venae cavae (anastomotic ramus), and the presence of both
      azygos veins. Among subjects with persistent left superior vena cava, the
      percentage of those with weak development of the anastomotic ramus (41.5 %) or
      absence of an anastomotic ramus (35.8 %) was 77.3 %. In addition, 54.7 % of
      subjects had a left azygos vein. However, 88.7 % of subjects had a right azygos
      vein. In this classification, the most frequently observed types included the
      presence of both superior venae cavae, an anastomotic ramus, and both azygos
      veins (20.8 %). During student dissection practice sessions performed on 337
      cadavers that were carried out from 2002 through 2010, a subject having a left
      superior vena cava (in 2002) and a subject having both superior venae cavae (in
      2003) were detected. The former case was reported previously. The latter case is
      reported in this paper. The incidence of persistent left superior vena cava was
      0.59 % (2/337 cadavers).

PMID- 22948518
TI  - Subtotal intracardiac fragmentation of a pulmonary artery catheter during cardiac
      surgery: a rare complication of bipolar atrial ablation.

PMID- 22948519
TI  - Serum ghrelin levels and the effects of antidepressants in major depressive
      disorder and panic disorder.
AB  - BACKGROUND: Two opposing models for the action of ghrelin in the behavioral
      responses to stress were recently proposed. Some studies suggest that an increase
      in ghrelin contributes to the mechanisms responsible for the development of
      stress-induced depression and anxiety, while others suggest that it helps
      minimize what otherwise would be more severe manifestations of depression and
      anxiety following stress. METHODS: We measured serum ghrelin levels, Profile of
      Mood States (POMS) scores and State-Trait Anxiety Inventory scores in
      nonresponders (treatment-resistant patients; 30) and responders (38) with major
      depressive disorder (MDD), nonresponders (29) and responders (51) with panic
      disorder and 97 healthy controls. RESULTS: The ghrelin concentration in
      nonresponders with MDD was higher than that of responders with MDD and normal
      controls. The ghrelin concentration in nonresponders with panic disorder was
      higher than that of normal controls. POMS vigor scores in patients with MDD and
      panic disorder were significantly decreased compared with those in healthy
      controls. Other POMS scores in patients with MDD and panic disorder were
      significantly increased compared with those of healthy controls. Trait and state
      anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients
      were higher than those in healthy controls. CONCLUSIONS: These results indicate
      that decreased serum ghrelin levels might be associated with antidepressant
      treatment to confer the maximum therapeutic effect in patients with MDD and panic
      disorder.

PMID- 22948520
TI  - Fabrication and characterization of solid-state nanopore arrays for high
      throughput DNA sequencing.
AB  - We report the fabrication and characterization of uniformly sized nanopore
      arrays, integrated into an optical detection system for high-throughput DNA
      sequencing applications. Nanopore arrays were fabricated using focused ion beam
      milling, followed by TiO(2) coating using atomic layer deposition. The TiO(2)
      layer decreases the initial pore diameter down to the sub-10 nm range, compatible
      with the requirements for nanopore-based sequencing using optical readout. We
      find that the TiO(2) layers produce a lower photoluminescence background as
      compared with the more widely used Al(2)O(3) coatings. The functionality of the
      nanopore array was demonstrated by the simultaneous optical detection of DNA
      quantum dot conjugates, which were electro-kinetically driven through the
      nanopores. Our optical scheme employs total internal reflection fluorescence
      microscopy to illuminate a wide area of the TiO(2)-coated membrane. A highly
      parallel system for observing DNA capture events in a uniformly sized 6 * 6
      nanopore array was experimentally realized.

PMID- 22948521
TI  - Disclosure of financial conflicts of interest: an evaluation of orthopaedic
      surgery patients' understanding.
AB  - BACKGROUND: Industry and orthopaedic surgeons often partner to develop new
      technology, which can lead to orthopaedic surgeons having financial conflicts of
      interest (FCOI). It is essential these FCOI be conveyed clearly to patients. It
      is unclear, however, whether and to what degree patients understand the
      ramifications of physician FCOI. QUESTIONS/PURPOSES: We evaluated (1) patients'
      concerns regarding their surgeon having FCOI or the presence of institutional
      FCOI, (2) the effect of surgeon FCOI on patients' willingness to have surgery,
      and (3) patients' understanding of FCOI. METHODS: We asked 101 patients (66%
      female) receiving total joint arthroplasty from the orthopaedic practices of two
      surgeons at an academic health center to complete a descriptive, correlational
      designed survey at their 6-week followup appointment. The data collected included
      patient demographics, knowledge of FCOI, and the influence of FCOI on patient
      attitudes toward surgery and their surgeon. RESULTS: A minority of patients (13%)
      reported discussing FCOI with prior physicians and only 55% agreed or strongly
      agreed a surgeon should disclose FCOI. Only 15% of patients believed such
      conflicts would make them less likely to have their surgeon operate on them.
      Level of education was weakly correlated (Spearman's rho = 0.29) with patient
      understanding of FCOI. CONCLUSIONS: Overall, patients had a poor understanding of
      FCOI. Both level of education and previous discussions of FCOI predicted better
      understanding. This study emphasizes communication of FCOI with patients needs to
      be enhanced.

PMID- 22948523
TI  - Rotating-platform has no surface damage advantage over fixed-bearing TKA.
AB  - BACKGROUND: Rotating-platform TKA, although purported to have superior
      kinematics, has shown no clinical advantages over those of fixed-bearing TKA. Our
      design-matched retrieval study aimed to investigate if differences in bearing
      wear damage exist between fixed- and mobile-bearing TKAs with similar condylar
      geometry. QUESTIONS/PURPOSES: We asked whether (1) the rotating platform's more
      conforming tibiofemoral articulation would be associated with less severe damage;
      (2) the location of damage and wear would be similar on the tibiofemoral or
      backside surfaces of two contemporary designs with similar condylar geometry; and
      (3) the combined damage and deformation measured as thickness would differ
      between the two designs. METHODS: We performed damage grading and damage mapping
      on 25 rotating-platform and 17 fixed-bearing inserts. The patient demographic
      data from each of these cohorts were comparable. Inserts were also laser-scanned
      from which we obtained thicknesses, and inferior surface three-dimensional scans,
      from which we determined dimensional changes. RESULTS: Rotating-platform and
      fixed-bearing inserts had similar tibiofemoral damage scores. However, the scores
      on the inferior surface of rotating platforms were greater, often as a result of
      third-body debris scratching observed on both damage mapping and three
      dimensional scans. The extent of damage as a function of surface area was greater
      for rotating platforms, consistent with the greater tibiofemoral conformity.
      Dimensional changes on the inferior surfaces of the fixed bearing followed
      loading areas of the knee. However, no differences were seen in the thicknesses
      between fixed- and rotating-platform bearings. CONCLUSIONS: The increased total
      damage score on the rotating platform, coupled with increased surface area
      damaged and the propensity for third-body debris, indicates no damage advantage
      to this mobile-bearing design.

PMID- 22948522
TI  - Computer-assisted total knee arthroplasty is currently of no proven clinical
      benefit: a systematic review.
AB  - BACKGROUND: Navigated total knee arthroplasty (TKA) may improve coronal alignment
      outliers; however, it is unclear whether navigated TKA improves the long-term
      clinical results of TKA. QUESTIONS/PURPOSES: Does the literature contain evidence
      of better long-term function and lower revision rates with navigated TKA compared
      with conventional TKA? METHODS: A systematic literature review was conducted of
      navigated TKA reviewing articles related to coronal alignment, clinical knee and
      function scores, cost, patient satisfaction, component rotation, anteroposterior
      and mediolateral stability, complications, and longer-term reports. RESULTS:
      Coronal plane alignment is improved with navigated TKA with fewer radiographic
      outliers. We found limited evidence of improvements in any other variable, and
      function was not improved. The duration of surgery is increased and there are
      unique complications related to navigated TKA. The long-term benefits of
      additional increase in accuracy of alignment are not supported by any current
      evidence. CONCLUSIONS: The findings in reports of navigated TKA should be
      interpreted with caution. There are few short- and medium- and no long-term
      studies demonstrating improved clinical outcomes using navigated TKA. Despite
      substantial research, contradictory findings coupled with reservations about the
      cost and efficacy of the technology have contributed to the failure of computer
      navigation to become the accepted standard in TKA. Longer-term studies
      demonstrating improved function, lower revision rates, and acceptable costs are
      required before navigated TKA may be widely adopted. In the future, with
      improvements in study design, methodology, imaging, navigation technology, newer
      functional outcome tools, and longer-term followup studies, we suspect that
      navigated TKA may demonstrate yet unrecognized benefits.

PMID- 22948524
TI  - Joint-preserving tumor resection and reconstruction using image-guided computer
      navigation.
AB  - BACKGROUND: Joint-preserving surgery is performed in select patients with bone
      sarcomas of extremities and allows patients to retain the native joint with
      better joint function. However, recurrences may relate to achieving adequate
      margins and there is frequently little room for error in tumors close to the
      joint surface. Further, the tumor margin on preoperative CT and/or MR images is
      difficult to transpose to the actual extent of tumor in the bone in the operating
      room. QUESTIONS/PURPOSES: We therefore determined whether joint-preserving tumor
      surgery could be performed accurately under image-guided computer navigation and
      determined local recurrences, function, and complications. METHODS: We
      retrospectively studied eight patients with bone sarcoma of extremities treated
      surgically by navigation with fused CT-MR images. We assessed the accuracy of
      resection in six patients by comparing the cross sections at the resection plane
      with complementary prosthesis templates. Mean age was 17 years (range, 6-46
      years). Minimum followup was 25 months (mean, 41 months; range, 25-60 months).
      RESULTS: The achieved resection was accurate, with a difference of 2 mm or less
      in any dimension compared to that planned in patients with custom prostheses. We
      noted no local recurrence at latest followup. The mean Musculoskeletal Tumor
      Society score was 29 (range, 28-30). There were no complications related to
      navigation planning and procedures. There was no failure of fixation at the
      remaining epiphysis. CONCLUSIONS: In selected patients, the computer-assisted
      approach facilitates precise planning and execution of joint-preserving tumor
      resection and reconstruction. Further followup assessment in a larger study
      population is required in these patients. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 22948525
TI  - Lessons learned from managing a prospective, private practice joint replacement
      registry: a 25-year experience.
AB  - BACKGROUND: In 1984, we developed a private practice joint replacement registry
      (JRR) to prospectively follow patients undergoing THA and TKA to assess clinical
      and radiographic outcomes, complications, and implant survival. Little has been
      reported in the literature regarding management of this type of database, and it
      is unclear whether and how the information can be useful for addressing longer
      term questions. QUESTIONS/PURPOSES: We answered the following questions: (1) What
      is the rate of followup for THA and TKA in our JRR? (2) What factors affect
      followup? (3) How successful is this JRR model in capturing data and what areas
      of improvement are identified? And (4) what costs are associated with maintaining
      this JRR? METHODS: We collected clinical data on all 12,047 patients having
      primary THA and TKA since 1984. Clinical and radiographic data were collected at
      routine followup intervals and entered into a prospective database. We searched
      this database to assess the rate of successful followup and data collection and
      to compare the effect of patient variables on followup. Costs related to database
      management were evaluated. RESULTS: Followup was poor at every time interval
      after surgery, with a tendency for worsening over time. Patients with a
      complication and those younger than 70 years tended to followup with greater
      frequency. There were difficulties with data capture and substantial expenses
      related to managing the database. CONCLUSIONS: Our findings highlight the
      difficulties in managing a JRR. Followup is poor and data collection is often
      incomplete. Newer technologies that allow easier tracking of patients and
      facilitate data capture may streamline this process and control costs.

PMID- 22948526
TI  - Reliability of lower-limb alignment measurements in patients with multiple
      epiphyseal dysplasia.
AB  - BACKGROUND: Although radiographic measurements are used in multiple epiphyseal
      dysplasia (MED) during correction of lower-limb alignment, the reliabilities of
      the measurements are unclear. QUESTIONS/PURPOSES: We determined interobserver and
      intraobserver reliabilities of the measurement methods used in evaluation of
      lower-limb alignment in MED. METHODS: After consensus building, we included 10
      radiographic measurement methods widely used to evaluate lower-limb alignment:
      mechanical tibiofemoral angle, anatomic tibiofemoral angle, mechanical axis
      deviation, joint line convergence angle, mechanical lateral distal femoral angle,
      anatomic lateral distal femoral angle, mechanical medial proximal tibial angle,
      anatomic medial proximal tibial angle, epimetaphyseal angle, and tibial
      metadiaphyseal angle. A study group consisting of 30 patients with MED was
      compared with a control group consisting of 30 sex- and age-matched patients with
      genu varum and genu valgum. Mean age in both groups was 11 years (study group:
      SD, 2 years; range, 6-16 years; control group: SD, 2 years; range, 6-15 years).
      Interobserver and intraobserver reliabilities of all radiographic measurement
      methods were obtained and expressed by intraclass correlation coefficients
      (ICCs). RESULTS: Mechanical tibiofemoral angle, anatomic tibiofemoral angle, and
      mechanical axis deviation were associated with high interobserver reliability
      (ICCs, 0.987, 0.985 and 0.982, respectively). Epimetaphyseal angle had the lowest
      reliability (ICC, 0.280). Intraobserver reliability exhibited similar trends,
      with mechanical axis deviation and mechanical tibiofemoral angle having the
      highest ICCs and epimetaphyseal angle the lowest. CONCLUSIONS: Mechanical
      tibiofemoral angle, anatomic tibiofemoral angle, and mechanical axis deviation
      are reasonably reliable measures of alignment in MED. The lateral distal femoral
      angle and medial proximal tibial angle (mechanical and anatomic) can be used as
      complementary measurement methods. LEVEL OF EVIDENCE: Level II, diagnostic study.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 22948527
TI  - High survival of modular tapered stems for proximal femoral bone defects at 5 to
      10 years followup.
AB  - BACKGROUND: Currently, the two most commonly used options for the revision of
      femoral components in North America are: cylindrical, nonmodular, cobalt-chromium
      stems and tapered, fluted, modular, titanium (TFMT) stems. Previous reports have
      cited high failure rates with cylindrical cobalt chrome stems in large femoral
      defects but the longer term survival of the fluted stems is unknown.
      QUESTIONS/PURPOSES: We examined the 5- to 10-year survival of TFMT stems
      implanted for severe femoral defects. METHODS: We reviewed all 65 patients with
      severe proximal bone defects revised with the TMFT stem between January 2000 and
      2006. Ten were lost to followup and seven were dead, leaving 48 patients for
      followup at 5 to 10 years (mean, 84 months; range, 60-120 months). All patients
      completed five quality-of-life (QOL) questionnaires. Radiographs were evaluated
      for loosening, subsidence, and preservation of proximal host bone stock. RESULTS:
      Implant survivorship was 90%. No patient underwent revision for either subsidence
      or loosening. Subsidence occurred in seven patients (average, 12.3 mm) but all
      achieved secondary stability. Five patients underwent revision as a result of
      fracture of the stem and all had the original standard stem design, which has
      since been modified. All five implant fractures occurred at the modular stem
      junction. Mean QOL outcomes were: WOMAC = 81 (pain), Oxford = 75, SF-12 = 54
      (mental) and 38 (physical), UCLA Activity = 4, and satisfaction overall = 73.
      CONCLUSIONS: Midterm survivorship of modular titanium stems in large femoral
      defects is high; however, ongoing surveillance of stem junctional fatigue life is
      required. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22948528
TI  - Acetabular cup design influences deformational response in total hip
      arthroplasty.
AB  - BACKGROUND: Press-fit acetabular components are susceptible to deformation in an
      underreamed socket, with excessive deformation of metal-on-metal (MOM) components
      potentially leading to increased torsional friction and micromotion.
      Specifically, however, it remains unclear how cup diameter, design, and time from
      implantation affect shell deformation. QUESTIONS/PURPOSES: We asked whether (1)
      changes in component geometry and material altered maximum shell deformation and
      (2) time-dependent deformational relaxation processes occurred. METHODS:
      Diametral deformation was quantified after press-fit implantation of metal shells
      into a previously validated polyurethane model. Experimental groups (n = 6-8)
      consisted of 48-, 54-, 60-, and 66-mm MOM cups of 6-mm wall thickness, 58-mm cups
      of 10-mm wall thickness, and CoCrMo and Ti6Al4V 58-mm modular cups. RESULTS:
      Greater cup diameter, thinner wall construction, and Ti6Al4V modular designs
      generated conditions for maximum shell deformation ranging from 0.047 to 0.267
      mm. Relaxation (18%-32%) was observed 120 hours postimplantation in thin-walled
      and modular designs. CONCLUSIONS: Our findings demonstrate a reduction of shell
      deformation over time and suggest, under physiologic loading, early component
      deformation varies with design. CLINICAL RELEVANCE: Component deformation should
      be a design consideration regardless of bearing surface. Designs neglecting to
      adequately address deformational changes in vivo could be susceptible to
      diminished cup survival, increased wear, and premature revision.

PMID- 22948529
TI  - 50 Years ago in CORR: Survival car II Murray E. Gibbens MD CORR 1962;23:299-300.

PMID- 22948530
TI  - Computer-assisted tumor surgery in malignant bone tumors.
AB  - BACKGROUND: Small recent case series using CT-based navigation suggest such
      approaches may aid in surgical planning and improve accuracy of intended
      resections, but the accuracy and clinical use have not been confirmed.
      QUESTIONS/PURPOSES: We therefore evaluated (1) the accuracy; (2) recurrences; and
      (3) function in patients treated by computer-assisted tumor surgery (CATS).
      METHODS: From 2006 to 2009, we performed CATS in 20 patients with 21 malignant
      tumors. The mean age was 31 years (range, 6-80 years). CT and MR images for 18
      cases were fused using the navigation software. Reconstructed two
      dimensional/three-dimensional images were used to plan the bone resection. The
      achieved bone resection was compared with the planned one by assessing margins,
      dimensions at the level of bone resection, or fitting of CAD custom prostheses.
      Function was assessed with the Musculoskeletal Tumor Society (MSTS) score. The
      minimum followup was 31 months (mean, 39 months; range, 5-69 months). RESULTS:
      Histological examination of all resected specimens showed a clear tumor margin.
      The achieved bone resection matched the planned with a difference of <= 2 mm. The
      achieved positions of custom prostheses were comparable to the planned positions
      when merging postoperative with preoperative CT images in five cases. Three of
      the four patients with local recurrence had tumors at the sacral region. The mean
      MSTS score was 28 (range, 23-30). CONCLUSION: CATS with image fusion allows
      accurate execution of the intended bone resection. It may be beneficial to
      resection and reconstruction in pelvic, sacral tumors and more difficult joint
      preserving intercalated tumor surgery. Comparative clinical studies with long
      term followup are necessary to confirm its efficacy. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22948531
TI  - Which implant is best after failed treatment for pathologic femur fractures?
AB  - BACKGROUND: Successful treatment of pathologic femur fractures can preserve a
      patient's independence and quality of life. The choice of implant depends on
      several disease- and patient-specific variables; however, its durability must
      generally match the patient's estimated life expectancy. Failures do occur,
      however, it is unclear which implants are associated with greater risk of
      failure. QUESTIONS/PURPOSES: We evaluated patients with femoral metastases in
      whom implants failed to determine (1) the rate of reoperation; (2) the timing of
      and most common causes for failure; and (3) incidence of perioperative
      complications and death. METHODS: From a prospectively collected registry, we
      identified 93 patients operated on for failed treatment of femoral metastases
      from 1990 to 2010. We excluded five patients who subsequently underwent
      amputations leaving 88 who underwent salvage procedures. These included
      intramedullary nails (n = 11), endoprostheses (n = 61), and plate fixation (n =
      16). The primary outcome was reoperation after salvage treatment. RESULTS:
      Seventeen of the 88 patients (19%) required subsequent reoperation a median of 10
      months (interquartile range, 4-14) from the time of salvage surgery: 15 for
      material failure, one for local progression of tumor, and one for a combination
      of these. Five patients died within 4 weeks of surgery. Although perioperative
      complications were higher in the endoprosthesis group and dislocations occurred,
      overall treatment failures after salvage surgery were lower in the that group
      (four of 61) compared the group with plate fixation (eight of 16) and
      intramedullary nail groups (five of 11). CONCLUSIONS: Despite relatively common
      perioperative complications, salvage using endoprostheses may be associated with
      fewer treatment failures as compared with internal fixation. LEVEL OF EVIDENCE:
      Level III, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22948532
TI  - Abnormal function of monoamine oxidase-A in comorbid major depressive disorder
      and cardiovascular disease: pathophysiological and therapeutic implications
      (review).
AB  - The association between major depressive disorder (MDD) and cardiovascular
      disease (CVD) is among the best described medical comorbidities. The presence of
      MDD increases the risk of cardiac admissions and mortality and increases
      healthcare costs in patients with CVD, and similarly, CVD affects the course and
      outcome of MDD. The potential shared biological mechanisms involved in these
      comorbid conditions are not well known. However, the enzyme monoamine oxidase-A
      (MAO-A), which has a key role in the degradation of catecholamines, has been
      associated with the pathophysiology and therapeutics of both MDD and CVD.
      Increased MAO-A activity results in the dysregulation of downstream targets of
      this enzyme and thus affects the pathophysiology of the two diseases. These
      deleterious effects include altered noradrenaline turnover, with a direct
      elevation in oxidative stress parameters, as well as increased platelet activity
      and cytokine levels. These effects were shown to be reversed by MAO inhibitors.
      Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is
      proposed, with focus on the shared pathophysiological mechanisms and the
      potential therapeutic relevance of agents targeting this enzyme.

PMID- 22948533
TI  - Is C60 buckminsterfullerene aromatic?
AB  - C(60) does not have "superaromatic" or even aromatic character, but is a
      spherically pi antiaromatic and enormously strained species. This explains its
      very large and positive heat of formation (610 +/- 30 kcal mol(-1)). The pi
      electron character of C(60) was analyzed by dissected nucleus independent
      chemical shifts (NICS). The results were employed to examine the scope and
      limitations of Hirsch's 2(N + 1)(2) spherical aromaticity rule for several
      globular cages. C(20)(2+) (18 pi electrons) and C(60)(10+) (50 pi electrons) are
      spherically pi aromatic, but C(20) (20 pi electrons) and C(60) (60 pi electrons)
      are spherically pi antiaromatic, due to the high paratropicity of their half
      filled pi subshells. Limitations for Hirsch's rule, for clusters with more than
      50 pi electrons, are illustrated by e.g. the pi aromaticity of the 66 pi electron
      C(60)(6-) and the lack of pi aromaticity of the 72 pi electron C(48)N(12) and
      C(60)(12-).

PMID- 22948534
TI  - Birds do it, bees do it, we do it: contributions of theoretical modelling to
      understanding the shape of ageing across the tree of life.
AB  - Organisms of different species age differently. Current theory explains why life
      should get worse, i.e. why patterns of increasing risk of death should evolve.
      However, for some species the risk of death remains constant or even falls with
      advancing age. Evolutionary theory to explain the observed diversity of shapes of
      ageing is lacking. Theoretical models can provide insights into this diversity.
      Comparing assumptions of models that find increasing mortality patterns with
      models that find a variety of patterns, including constant and falling mortality
      over age, I identify conditions that licence constant or negative shapes of
      ageing. The results suggest that patterns of improvement and maintenance over age
      emerge when models potentially allow organisms to (1) escape the 'damage
      ratchet', (2) achieve maintenance and repair in parallel, (3) face increasing
      future reproductive potential and (4) incorporate flexible trade-offs. With these
      insights, theoretical models contribute to hypotheses about which species may
      follow life history strategies of negligible or negative ageing.

PMID- 22948535
TI  - New frontiers in the design and synthesis of imaging probes for PET oncology:
      current challenges and future directions.
AB  - Despite being developed over 30 years ago, 2-deoxy-2-[(18)F]fluoro-D-glucose
      remains the most frequently used radiotracer in PET oncology. In the last decade,
      interest in new and more specific radiotracers for imaging biological processes
      of oncologic interest has increased exponentially. This review summarizes the
      strategies underlying the development of those probes together with their
      validation and status of clinical translation; a brief summary of new
      radiochemistry strategies applicable to PET imaging is also included. The article
      finishes with a consideration of the challenges imaging scientists must overcome
      to bring about increased adoption of PET as a diagnostic or pharmacologic tool.

PMID- 22948536
TI  - A comparative study of primary and recurrent human glioblastoma multiforme using
      the small animal imaging and molecular expressive profiles.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is the most malignant brain tumor with the
      characteristics of highly infiltrative growth and recurrent rate. In this study,
      we used animal imaging and molecular expressive profiles to investigate the
      characteristics of the primary tumor (GBM-3) cells and recurrent tumor (S1R1)
      cells from different GBM patients. PROCEDURES: Bioluminescent imaging and 3T
      magnetic resonance imaging (MRI) were used for assessing the orthotopical tumor
      development of GBM cells harboring a polycistronic reporter gene system. Western
      blot analysis and quantitative polymerase chain reaction were used to compare the
      molecular expressive profiles of two types of GBM cells. RESULTS: S1R1 cells
      exhibited apparent invasive ability compared to GBM-3 cells using in vitro
      invasion assay. In vivo bioluminescent imaging showed that intracranial tumors
      are formed by both types of GBM cells, but the bioluminescent signal was also
      detected in the lumbar region at late-stage tumor formed by S1R1 cells. The MRI
      showed that intracranial tumors formed by S1R1 cells were highly infiltrative
      compared to that formed by GBM-3 cells. Additionally, these two GBM types
      expressed different patterns of molecules associated with tumor development.
      Moreover, the suppressive effects of interleukine-23 (IL-23) on xenograft tumors
      formed by both GBM types were detected using bioluminescent imaging. CONCLUSION:
      The current data suggest that the in vivo growth behaviors and therapeutic
      responses of the primary and recurrent human GBMs were comparable using the
      reporter gene imaging, and different molecular expressive profiles exist between
      these two GBM types.

PMID- 22948538
TI  - Treatment patterns and outcomes in elderly patients with multiple myeloma.

PMID- 22948537
TI  - C/EBPbeta promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell
      exhaustion.
AB  - The BCR-ABL fusion oncoprotein accelerates differentiation and proliferation of
      myeloid cells during the chronic phase of chronic myeloid leukemia (CP-CML).
      Here, the role of CCAAT/enhancer binding protein beta (C/EBPbeta), a regulator
      for 'emergency granulopoiesis,' in the pathogenesis of CP-CML was examined.
      C/EBPbeta expression was upregulated in Lineage(-) CD34(+) CD38(-) hematopoietic
      stem cells (HSCs) and myeloid progenitors isolated from bone marrow of patients
      with CP-CML. In EML cells, a mouse HSC line, BCR-ABL upregulated C/EBPbeta, at
      least in part, through the activation of STAT5. Myeloid differentiation and
      proliferation induced by BCR-ABL was significantly impaired in C/EBPbeta
      deficient bone marrow cells in vitro. Mice that were transplanted with BCR-ABL
      transduced C/EBPbeta knockout bone marrow cells survived longer than mice that
      received BCR-ABL-transduced wild-type (WT) bone marrow cells. Significantly
      higher levels of leukemic stem cells were maintained in BCR-ABL-transduced
      C/EBPbeta-deficient cells than in BCR-ABL-transduced WT cells. These results
      suggest that C/EBPbeta is involved in BCR-ABL-mediated myeloid expansion. Further
      elucidation of the molecular mechanisms underlying the C/EBPbeta-mediated stem
      cell loss might reveal a novel therapeutic strategy for eradication of CML stem
      cells.

PMID- 22948539
TI  - Pulsed electromagnetic field stimulates osteoprotegerin and reduces RANKL
      expression in ovariectomized rats.
AB  - Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral
      density in osteoporosis patients and prevent bone loss in ovariectomized rats.
      But the mechanisms through which PEMF elicits these favorable biological
      responses are still not fully understood. Receptor activator of nuclear factor
      kappaB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly
      secreted by osteoblasts and play a central role in differentiation and functional
      activation of osteoclasts. The purpose of this study was to investigate the
      effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3
      month-old female Sprague-Dawley rats were randomly divided into three groups:
      sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with
      PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF
      increased serum 17beta-estradiol level, reduced serum tartrate-resistant acid
      phosphatase level, increased bone mineral density, and inhibited deterioration of
      bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress
      RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In
      conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone
      loss through regulating the expression of RANKL and OPG.

PMID- 22948540
TI  - SKG arthritis as a model for evaluating therapies in rheumatoid arthritis with
      special focus on bone changes.
AB  - The aim was to further characterize the SKG model of rheumatoid arthritis (RA)
      and its potential for studying intervention treatments, with special focus on
      bone targeting therapies. Three individual studies were conducted, using a total
      of 71 SKG mice, comparing arthritis induction with mannan versus zymosan A,
      female versus male mice, and the effect of dexamethasone intervention treatment
      initiated at different time points after arthritis induction. Hind paws were
      embedded undecalcified in methyl methacrylate, and sections were stained with
      Masson-Goldner trichrome. Areal Bone Mineral Density (aBMD) of the femora was
      determined with pDXA. RNA was extracted from the hind paws followed by the
      quantification by reverse transcriptase PCR. SKG mice stimulated with mannan
      presented a higher arthritis score than mice stimulated with zymosan A. Female
      SKG mice developed a more severe arthritis than male SKG mice. Dexamethasone
      inhibited arthritis clinically as well as histologically when the treatment was
      initiated prophylactically or within the first week of arthritis. Femoral aBMD
      was lower in animals with arthritis than in control animals. The RANKL RNA
      expression was elevated in arthritic mice, whereas OPG RNA expression was
      unchanged. The results suggest mannan as arthritis inductor and female instead of
      male mice in experiments as well as an optimal time window for the initiation of
      treatment. Systemic bone loss as well as local up regulation of RANKL was present
      early in SKG arthritis. These results demonstrate that SKG arthritis is a
      suitable new model for evaluating therapies in RA.

PMID- 22948542
TI  - Jaccoud's arthropathy: proper classification criteria and treatment are still
      needed.

PMID- 22948541
TI  - Contribution of toll-like receptor 9 gene single-nucleotide polymorphism to
      systemic lupus erythematosus.
AB  - There are several studies on the association of TLR9 polymorphisms with systemic
      lupus erythematosus (SLE) in different ethnicities; however, the results are
      inconsistent. Therefore, we studied the distribution of the TLR9 C > T (rs352140)
      polymorphism in patients with SLE (n = 254) and controls (n = 521) in a Polish
      population. We did not observe significant differences in the prevalence of the
      TLR9 C > T genotype and alleles between patients with SLE and controls. However,
      we found a contribution of the T/T and T/C genotypes to renal [OR = 2.949 (95 %
      CI = 1.523-5.711, p = 0.001), (p corr = 0.017)] and immunologic disorders [OR =
      2.938 (95 % CI 1.500-5.755, p = 0.0012), (p corr = 0.0204)] in SLE patients.
      Moreover, we observed a significant association between the TLR9 T/T and T/C
      genotypes and the presence of anti-dsDNA Ab [OR = 3.682 (1.647-8.230, p = 0.001),
      (p corr = 0.017)]. Our studies suggest that the TLR9 C > T (rs352140)
      polymorphism might contribute to renal and immunologic disorders and to the
      presence of anti-dsDNA Ab.

PMID- 22948543
TI  - Ulnar nerve measurements in healthy individuals to obtain reference values.
AB  - The aim of this study was to obtain the ultrasonographical reference values of
      ulnar nerve cross-sectional areas at the common areas of nerve entrapment as well
      as any differences related to age, sex, weight, height, dominant arm. Cross
      sectional areas of the ulnar nerves of 72 healthy volunteers were measured
      bilaterally at the level of the epicondyle, 2 cm proximal to and 2 cm distal to
      the epicondyle, just at the entrance of cubital tunnel, at arterial split, at
      Guyon's canal. Age, sex, body weight, height, body mass index, and dominant
      extremity were recorded. The mean ulnar nerve cross-sectional area was 5.8 +/-
      1.1 mm(2) at 2 cm proximal to medial epicondyle, 6.2 +/- 1.1 mm(2) at the medial
      epicondyle, 5.6 +/- 0.9 mm(2) at the entrance of the cubital tunnel, 5.6 +/- 1.0
      mm(2) at 2 cm distal to medial epicondyle (inside the flexor carpi ulnaris), 5.0
      +/- 0.6 mm(2) at arterial split, and 4.9 +/- 0.6 mm(2) at Guyon's canal. There
      was statistically no difference between the dominant and nondominant sides (p >
      0.05). Females had statistically smaller nerves than males (p < 0.05). There was
      a significant correlation with height at all levels; also, weight was
      significantly correlated with cross-sectional areas except at two levels: tip of
      medial epicondyle and 2 cm distal. This study provides normative data of ulnar
      nerve ultrasonography and as well as any differences related to age, sex, height,
      weight, and dominant arm.

PMID- 22948544
TI  - Quantum dot based turn-on fluorescent probes for anion sensing.
AB  - The design of fluorescent probes for turn-on sensing of anions has been
      especially significant because it can effectively enhance sensing sensitivity by
      decreasing the background interference. In the present work, we have
      systematically studied the potential applications of fluorescent quantum dots
      (QDs) in turn-on anion sensing. The fluorescence of QDs are firstly quenched by
      three different mechanisms, i.e. fluorescence resonance energy transfer, electron
      transfer and surface states modulated fluorescence. The fluorescence of the pre
      quenched QDs can then be recovered by various anions due to the modulating
      effects of added anions on the interaction between QDs and QDs, the interaction
      between QDs and quenchers, and the surface chemistry of the quenched QDs,
      respectively. The results described here indicate that turn-on sensing of various
      anions by QDs-based systems can be achieved by rationally choosing fluorescence
      modulating strategies, demonstrating the versatility of QDs in the corresponding
      applications.

PMID- 22948545
TI  - Going against the tide--how encephalitogenic T cells breach the blood-brain
      barrier.
AB  - During multiple sclerosis or its animal model, experimental autoimmune
      encephalomyelitis, circulating immune cells enter the central nervous system
      (CNS) causing neuroinflammation. Extravasation from the blood circulation across
      the vessel wall occurs through a multistep process regulated by adhesion and
      signal transducing molecules on the immune cells and on the endothelium. Since
      the CNS is shielded by the highly specialized blood-brain barrier (BBB), immune
      cell extravasation into the CNS requires breaching this particularly tight
      endothelial border. Consequently, travelling into the CNS demands unique
      adaptations which account for the extreme tightness of the BBB. Modern imaging
      tools have shown that after arresting on BBB endothelium, in vivo or in vitro
      encephalitogenic effector/memory T cells crawl for long distances, possibly
      exceeding 150 um along the surface of the BBB endothelium before rapidly crossing
      the BBB. Interestingly, in addition to the distance of crawling, the preferred
      direction of crawling against the flow is unique for T cell crawling on the
      luminal surface of CNS microvessels. In this review, we will summarize the
      cellular and molecular mechanisms involved in the unique T cell behavior that is
      obviously required for finding a site permissive for diapedesis across the unique
      vascular bed of the BBB.

PMID- 22948546
TI  - Concurrent cytomegalovirus and herpes simplex virus infection in pemphigus
      vulgaris treated with rituximab and prednisolone.

PMID- 22948547
TI  - Developmental plasticity of endocrine disorders in obesity model primed by early
      weaning in dams.
AB  - Early weaning is associated with changes in the developmental plasticity. Here,
      we studied the adipocytes morphology, adipokines expression or content in adipose
      tissue as well as adrenal and thyroid function of neonate and adult offspring
      primed by early weaning. After birth, lactating rats were divided into 2 groups:
      EW (early weaning)--dams were wrapped with a bandage to block access to milk
      during the last 3 days of lactation, and Control--dams whose pups had free access
      to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had
      lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively),
      body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but
      higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal
      evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and
      TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat
      mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase),
      higher leptin (+95%) and ADRbeta3 (2-fold increase) content in visceral adipose
      tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%)
      but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher
      adrenal catecholamine content (+31%), but no changes in serum corticosterone or
      thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which
      can be associated with the adipocyte hypertrophy at adulthood. The marked changes
      in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found
      in obesity, contributing to the development of other cardiovascular and metabolic
      disturbances.

PMID- 22948549
TI  - Potential ramifications of DSM-5 classification of autistic disorders: comments
      from a clinician's perspective.

PMID- 22948548
TI  - Parent and pediatrician perspectives regarding the primary care of children with
      autism spectrum disorders.
AB  - Parents of children with autism spectrum disorders (ASD) (n = 144) and primary
      care providers (PCPs) (n = 144) completed similar surveys assessing the ability
      of the PCP to address ASD-specific needs. Parents also rated their PCP's ability
      to deliver family-centered care. A majority of parents rated their PCP's ability
      as "not good" in addressing 14 of 17 ASD-specific needs, while a majority of PCPs
      rated themselves as "good" in addressing 10 of 17 areas. On 7 of 17 items,
      parents rated their PCPs lower than PCPs rated themselves. Parents who reported
      receiving family-centered care were more likely to rate the PCP's ability to meet
      ASD specific needs as "good". Both parents and PCPs identified areas for
      improvement in caring for children with ASD.

PMID- 22948550
TI  - Effectiveness of low-frequency rTMS and intensive speech therapy in poststroke
      patients with aphasia: a pilot study based on evaluation by fMRI in relation to
      type of aphasia.
AB  - AIM: To assess the safety and clinical efficacy of low-frequency repetitive
      transcranial magnetic stimulation (LF-rTMS) combined with intensive speech
      therapy (ST) in poststroke patients with aphasia. SUBJECTS AND METHODS: Twenty
      four patients with left-hemispheric stroke and aphasia were subjected. During 11
      day hospitalization, each patient received 10 treatment sessions consisting of 40
      min 1-Hz LF-rTMS and 60-min intensive ST, excluding Sundays. The scalp area for
      stimulation was selected based on the findings of fMRI with language tasks and
      the type of aphasia. LF-rTMS was applied to the inferior frontal gyrus (IGF) for
      patients with nonfluent aphasia and to the superior temporal gyrus (STG) for
      patients with fluent aphasia. RESULTS: On pretreatment fMRI, the most activated
      areas were in the left hemisphere (n=16) and right hemisphere (n=8). The types of
      aphasia were nonfluent (n=14) and fluent (n=10). The LF-rTMS was applied to the
      right STG (n=5), left STG (n=5), right IFG (n=11) and left IFG (n=3). Nonfluent
      aphasic patients showed significant improvement of auditory comprehension,
      reading comprehension and repetition. Fluent aphasic patients showed significant
      improvement in spontaneous speech only. CONCLUSION: The fMRI with aphasic type
      based therapeutic LF-rTMS/intensive ST for chronic aphasia seems feasible and a
      potentially useful neurorehabilitative protocol.

PMID- 22948552
TI  - A psychoanalytic grave walk--Scenic memory of the Shoah. On the transgenerational
      transmission of extreme trauma in Germany.
AB  - In this article we describe a phase of a long-term psychoanalysis of a daughter
      of Shoah Survivors. The article is part of a research project conducted at the
      Sigmund Freud-Institute in Frankfurt/Main. The focus of the study is on the
      transmission of extreme trauma from the First to the Second Generation, with
      special reference to Germany. "Scenic memory of the Shoah" is presented as a
      concept that stresses the non-verbal, unconscious communication between the
      generations. The so-called "concretistic" behavior of the Second Generation,
      which has been described in the literature, is conceptualized here as scenic
      memory of the traumatic experiences during Nazi persecution, that is, a highly
      symbolic and metaphorical expression of the extreme trauma handed down to the
      patient by the parents.

PMID- 22948551
TI  - Silicate-substituted calcium phosphate as a bone graft substitute in surgery for
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN AND OBJECTIVE: The purpose of this prospective clinical study is to
      evaluate the clinical and radiographic outcomes using a silicate-substituted
      calcium phosphate (Si-CaP) as a bone graft substitute in surgery for adolescent
      idiopathic scoliosis (AIS). In posterior corrective surgery for AIS, harvesting
      autologous bone from the iliac crest still represents the gold standard to
      augment the local bone graft though it is comparatively invasive and associated
      with donor site morbidity. Si-CaP enriched with bone marrow aspirate (BMA) might
      be an appropriate bone graft extender to overcome these difficulties. METHODS:
      Eighteen female and three male patients with AIS who underwent corrective
      posterior instrumentation were observed clinically and radiographically for a
      minimum of 24 months. In all cases, 20-40 ml Si-CaP granules (ACTIFUSE) mixed
      with BMA from vertebral bodies was used to extend the local bone graft. Fusion
      was assessed by standardized conventional radiographs regarding loss of
      correction and implant failure. Clinical outcome was evaluated with use of the
      Scoliosis Research Society-22 patient Questionnaire (SRS-22) and a Visual Analog
      Scale (VAS) for back pain. RESULTS: Cobb angle of major curves averaged 63
      degrees  preoperatively, 22 degrees  after surgery, and 24 degrees  at final
      follow-up, with a maximum loss of correction of 7 degrees  recorded after 4
      months. No adverse effects related to the study material had been observed. In
      all patients, there was no evidence of implant failure, and formation of an
      increasingly densifying 'fusion mass' was visible, as assessed by conventional
      radiography. VAS score for back pain averaged 1.7 before surgery, 2.3 at
      discharge, and 1.5 at final follow-up. Outcome assessment using the SRS-22
      revealed a significantly enhanced overall health-related quality of life (84 vs.
      74 % before surgery; P = 0.0005) due to a significant improvement of the domains
      'self image' (77 vs. 59 %; P = 0.0002) and 'pain' (88 vs. 80 %; P = 0.02).
      Patients' management satisfaction averaged 93 %. CONCLUSIONS: Si-CaP augmented
      with BMA from vertebral bodies seems to prove an effective, safe, and easy to
      handle bone graft extender in scoliosis surgery and thus a suitable alternative
      to bone harvesting procedures.

PMID- 22948553
TI  - Critical transference in a case of severe epilepsy.
AB  - In this paper, the author presents a summary of a brief treatment with a young
      woman, suffering from severe epileptic illness, which describes the mutuality of
      cross-transferences of deep and intense feelings and the unorthodox way to
      receive, to take in persons affected with critical phenomena. This treatment was
      deeply influenced by the traumatic triad, borrowed from Ferenczi: "amnesia,
      anaesthesia, aboulia," the ways of forgetting (or erasing) the past/the
      present/the future. The investigation led us to clarify, on the one hand, the
      incestophilic--or perhaps incestuous--source in the family, and on the other, the
      burdensome and tragic genealogy and history of each parent. At the end of this
      short treatment, which took place at a frequency of one session a week (with the
      patient sitting, standing, lying on the floor; with sometimes severe fits,
      deliria, threats; bringing of letters, texts, drawings; and a few phone calls),
      there was an alleviation of the critical phenomena and revival.

PMID- 22948554
TI  - Empathy deficit in antisocial personality disorder: a psychodynamic formulation.
AB  - Empathic difficulty is a highly consequential characteristic of antisocial
      personality structure. The origin, maintenance, and possible resolution of this
      profound deficit are not very clear. While reconstructing empathic ability is of
      primary importance in the treatment of antisocial personality, not many proven
      procedures are in evidence. In this article, the author offers a psychodynamic
      formulation of the origin, character, and maintenance of the empathic deficiency
      in antisocial personality. The author discusses some of the treatment
      implications from this dynamic formulation.

PMID- 22948555
TI  - Moments of real relationship in psychoanalytic supervision.
AB  - What role does the real relationship play in psychoanalytic supervision? While
      the real relationship's role has long been and continues to be considered with
      regard to psychoanalysis, it has received virtually no attention in the
      supervision literature. In this paper, using Horney's construct of the real self
      as conceptual anchor, I attempt to: (1) situate the real relationship squarely
      within the borders of the psychoanalytic supervision relationship; (2) examine
      the relevance of real relationship phenomena for the supervision experience; (3)
      provide some simple, ordinary yet meaningful examples of case dialogue that
      illustrate moments of real relationship in supervision; and (4) introduce the
      concept of real relationship rupture and consider its potential ramifications for
      and impact upon the supervisor-supervisee relationship. Just as ruptures can
      occur in the supervisory alliance, I propose that ruptures can also transpire in
      the supervisory real relationship, have the potential to reverberate throughout
      the entirety of the supervision experience, and depending upon how they are
      handled, can prove either constructive and relationally energizing and enlivening
      or enervating and eviscerating to supervision process and outcome.

PMID- 22948556
TI  - How does neurobiological research influence psychoanalytic treatments?--Clinical
      observations and reflections from a study on the interface of clinical
      psychoanalysis and neuroscience.
AB  - One of the counterarguments against empirical research in psychoanalysis is that
      research negatively influences the treatment situation. In this paper, the impact
      of a neurobiological study on psychoanalytically oriented treatments is presented
      from three different perspectives: patients' views, a study group of
      participating psychoanalysts and a clinical case example. Twenty chronically
      depressed patients, 20 healthy controls and 16 psychoanalysts participated in the
      project on research. Results show a clear influence of the neurobiological study
      on the course of treatments. Patients consistently reported that study
      participation had a positive impact on their treatment experiences. However,
      study participation was conflictual for the psychoanalysts and forced them to
      carefully reflect on their unconscious and conscious involvement to establish a
      psychoanalytic stance independent from empirical research.

PMID- 22948560
TI  - Social inequalities in depression and suicidal ideation among older primary care
      patients.
AB  - PURPOSE: Depression and suicide are major public health concerns, and are often
      unrecognized among the elderly. This study investigated social inequalities in
      depressive symptoms and suicidal ideation among older adults. METHODS: Data come
      from 1,226 participants in PROSPECT (Prevention of Suicide in Primary Care
      Elderly: Collaborative Trial), a large primary care-based intervention trial for
      late-life depression. Linear and logistic regressions were used to analyze
      depressive symptoms and suicidal ideation over the 2-year follow-up period.
      RESULTS: Mean Hamilton Depression Rating Scale (HDRS) scores were significantly
      higher among participants in financial strain [regression coefficient (b) = 1.78,
      95 % confidence interval (CI) = 0.67-2.89] and with annual incomes below $20,000
      (b = 1.67, CI = 0.34-3.00). Financial strain was also associated with a higher
      risk of suicidal ideation (odds ratio = 2.35, CI = 1.38-3.98). CONCLUSIONS: There
      exist marked social inequalities in depressive symptoms and suicidal ideation
      among older adults attending primary care practices, the setting in which
      depression is most commonly treated. Our results justify continued efforts to
      understand the mechanisms generating such inequalities and to recognize and
      provide effective treatments for depression among high-risk populations.

PMID- 22948561
TI  - Living donor intestinal transplant using a standardized technique: first report
      from India.
AB  - AIM: We describe the first living donor intestinal transplant (LDIT) in India and
      discuss the indications and problems of this complex procedure. METHODS: A 43
      year-old male patient required massive bowel resection for gangrene due to
      thrombosis of the superior mesenteric artery. He was maintained on parenteral
      nutrition but developed cholestasis and well as repeated catheter related
      infections with progressive loss of venous access due to thrombosis of central
      veins. A LDIT was performed using 200 cm of small intestine from the patient's
      son. The graft was based on the continuation of the superior mesenteric vessels
      beyond the ileocolic branch. The artery was anastomosed directly to the aorta and
      the vein to the venacava. RESULTS: The graft functioned well and he was weaned
      off parenteral nutrition. However, he later developed complications (wound
      dehiscence and enterocutaneous fistula) and developed sepsis. He succumbed to
      sepsis with a functioning graft 6 weeks after the transplant. The donor recovered
      uneventfully and was discharged on the 4th postoperative day. CONCLUSIONS: LDIT
      can be life saving in patients with intestinal failure and failure of parenteral
      nutrition. There is a need to introduce this modality in India. In a setting of
      scarcity of deceased donor organs the living donor option has advantages.

PMID- 22948562
TI  - Major liver resection without preoperative biliary drainage in jaundiced patients
      with hilar biliary obstruction.
AB  - BACKGROUND: The need for routine use of preoperative biliary drainage (PBD) for
      major liver resection in jaundiced patients has recently been questioned.
      METHODS: We present our experience of 22 consecutive patients with hilar biliary
      obstruction who underwent major liver resection without PBD between January 2007
      and January 2011. RESULTS: Twenty-two patients with hilar biliary obstruction
      underwent major liver resection without PBD over a 4-year period; nineteen had
      malignant and 3 benign hilar strictures. Fifteen patients underwent right
      hepatectomy (7) or right trisectionectomy (8) and seven underwent left
      hepatectomy. Segment 4a was spared in all patients who underwent right
      trisectionectomy. Six patients had concomitant portal vein resection. Fourteen
      patients had varying degrees of lobar atrophy. The median preoperative bilirubin
      was 18 mg % (range 9.1 to 27 mg %). The median blood transfusion requirement was
      2 units (range 1-6). There was one postoperative death from portal vein
      thrombosis. Three patients who underwent greater than 50 % resection developed
      postoperative ascites. CONCLUSIONS: Major liver resection leaving a liver remnant
      of 50 % is safe in jaundiced patients without PBD even when portal vein
      reconstruction is necessary. PBD should be used selectively.

PMID- 22948563
TI  - Nanoconfinement in activated mesoporous carbon of calcium borohydride for
      improved reversible hydrogen storage.
AB  - Mesoporous carbon frameworks were synthesized using the soft-template method.
      Ca(BH(4))(2) was incorporated into activated mesoporous carbon by the incipient
      wetness method. The activation of mesoporous carbon was necessary to optimize the
      surface area and pore size. Thermal programmed absorption measurements showed
      that the confinement of this borohydride into carbon nanoscaffolds improved its
      reversible capacity (relative to the reactive portion) and performance of
      hydrogen storage compared to unsupported borohydride. Hydrogen release from the
      supported hydride started at a temperature as low as 100  degrees C and the
      dehydrogenation rate was fast compared to the bulk borohydride. In addition, the
      hydrogen pressure necessary to regenerate the borohydride from the
      dehydrogenation products was reduced.

PMID- 22948565
TI  - Competing 1pisigma* mediated dynamics in mequinol: O-H versus O-CH3
      photodissociation pathways.
AB  - Deactivation of excited electronic states through coupling to dissociative
      (1)pisigma* states in heteroaromatic systems has received considerable attention
      in recent years, particularly as a mechanism that contributes to the ultraviolet
      (UV) photostability of numerous aromatic biomolecules and their chromophores.
      Recent studies have expanded upon this work to look at more complex species,
      which involves understanding competing dynamics on two different (1)pisigma*
      potential energy surfaces (PESs) localized on different heteroatom hydride
      coordinates (O-H and N-H bonds) within the same molecule. In a similar spirit,
      the work presented here utilizes ultrafast time-resolved velocity map ion imaging
      to study competing dissociation pathways along (1)pisigma* PESs in mequinol (p
      methoxyphenol), localized at O-H and O-CH(3) bonds yielding H atoms or CH(3)
      radicals, respectively, over an excitation wavelength range of 298-238 nm and at
      200 nm. H atom elimination is found to be operative via either tunneling under a 
      conical intersection (CI) (298 >=    lambda    >= 280 nm) or ultrafast internal
      conversion through appropriate CIs (lambda    <= 245 nm), both of which provide
      mechanisms for coupling onto the dissociative  state associated with the O-H
      bond. In the intermediate wavelength range of 280 >=    lambda    >= 245 nm, 
      mediated H atom elimination is not observed. In contrast, we find that  state
      driven CH(3) radical elimination is only observed in the excitation range 264 >= 
      lambda    >= 238 nm. Interpretation of these experimental results is guided by:
      (i) high level complete active space with second order perturbation theory
      (CASPT2) calculations, which provide 1-D potential energy cuts of the ground and
      low lying singlet excited electronic states along the O-H and O-CH(3) bond
      coordinates; and (ii) calculated excitation energies using CASPT2 and the
      equation-of-motion coupled cluster with singles and doubles excitations (EOM
      CCSD) formalism. From these comprehensive studies, we find that the dynamics
      along the O-H coordinate generally mimic H atom elimination previously observed
      in phenol, whereas O-CH(3) bond fission in mequinol appears to present notably
      different behavior to the CH(3) elimination dynamics previously observed in
      anisole (methoxybenzene).

PMID- 22948564
TI  - Biosynthesis of clavam metabolites.
AB  - Naturally occurring clavam metabolites include the valuable beta-lactamase
      inhibitor, clavulanic acid, as well as stereochemical variants with side-chain
      modifications, called the 5S clavams. Because of the clinical importance of
      clavulanic acid, most studies of clavam biosynthesis are based on the industrial
      producer species Streptomyces clavuligerus. Well-characterized early steps in
      clavam biosynthesis are outlined, and less well understood late steps in 5S
      clavam biosynthesis are proposed. The complex genetic organization of the clavam
      biosynthetic genes in S. clavuligerus is described and, where possible,
      comparisons with other producer species are presented.

PMID- 22948566
TI  - Selected cytokine profiles during remission in bipolar patients.
AB  - OBJECTIVES: The aim of the study was to examine the cytokine status in bipolar
      patients during immediate remission after acute episodes of mania or depression
      and in patients with sustained (>=6 months) remission, compared with healthy
      controls. METHODS: The study was performed on 121 bipolar patients, of whom 35
      were in immediate remission after mania, 41 were in immediate remission after
      depression, and 45 were in >6-month remission on lithium monotherapy or lithium
      combined with other drugs. The control group consisted of 78 healthy individuals
      without any history of psychiatric or immunological illnesses. Serum
      concentrations of IL-1beta, IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma were
      determined using the Human Th1/Th2 Cytometric Bead Array method. RESULTS: The
      concentration of IL-10 was higher in patients in remission after mania and the
      concentration of IFN-gamma was higher in those in remission after depression than
      in healthy controls. On the other hand, cytokine concentrations in patients with
      sustained remission were not different from those of healthy subjects.
      CONCLUSIONS: The results obtained in this study show that sustained remission in
      bipolar patients achieved mostly by lithium maintenance brings the cytokine
      status to a level similar to healthy control subjects.

PMID- 22948567
TI  - Accelerated photo-transformation of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)
      in water by dissolved organic matter.
AB  - The ubiquitous dissolved organic matter (DOM) has an important influence on
      transformation of organic contaminants through the production of reactive
      substances, such as (*)OH, (1)O(2), and (3)DOM*. The photolysis of a higher
      chlorinated polychlorinated biphenyl (PCB) congener (2,2',4,4',5,5'
      hexachlorobiphenyl, PCB 153) under simulated sunlight in presence of humic acid
      (HA) was investigated. Degradation of PCB 153 was accelerated significantly by
      the addition of HA, with a rate constant of 0.0214, 0.0413, and 0.0358 h(-1) in
      the initial 18 h of irradiation in presence of 1, 5, and 20 mg/L HA,
      respectively. The main photodegradation products analyzed by gas chromatography
      mass spectrometry were 4-hydroxy-2,2',4',5,5'-pentaCB and 2,4,5-trichlorobenzoic
      acid. Main reactive species involved were determined by the electron spin
      resonance spectroscopy, including (1)O(2) and (*)OH. Special scavengers were
      added to elucidate the photolysis mechanisms. By using the specific scavengers,
      it turned out that (*)OH accounted for 29.3 % of the degradation, and the intra
      DOM reactive species ((1)O(2), (*)OH, and (3)DOM*) accounted for 59.6 % of the
      degradation. Photo-transformation sensitized by DOM, which involves both aqueous
      and intra-DOM reactions of PCBs with reactive species, may be one of the most
      important mechanisms for natural attenuation of PCBs.

PMID- 22948568
TI  - Evaluation of the ELOVL4, PRPH2 and ABCA4 genes in patients with Stargardt
      macular degeneration.
AB  - Mutations in the ATP-binding cassette, subfamily A, member 4 (ABCA4), elongation
      of very long chain fatty acids 4 (ELOVL4) and peripherin-2 (PRPH2) genes have
      been identified in patients with Stargardt macular degeneration (STGD). The aim
      of this study was to investigate which of these genes is responsible for
      susceptibility in Chinese patients. A total of 41 probands with STGD or suspected
      STGD were enrolled in the study. The coding regions and adjacent intronic
      sequences of the ELOVL4 and PRPH2 genes and 3 coding exons of the ABCA4 gene were
      amplified by polymerase chain reaction (PCR). The nucleotide sequences of the
      amplicons were determined by Sanger sequencing. Three novel heterozygous missense
      mutations in the ABCA4 gene were identified: c:2633C>A (p:Ser878X), c:5646G>A
      (p:Met1882Ile) and c:6389T>A (p:Met2130Lys). These mutations were not present in
      176 normal individuals and were predicted to be pathogenic. Two benign variations
      were found: a reported variation, c:5682G>C in ABCA4 and a novel variation,
      c:699G>A in ELOVL4. In addition, 5 single nucleotide polymorphisms (SNPs:
      rs3812153, rs7764439, rs390659, rs434102 and c:929G>A) were detected in ELOVL4
      and PRPH2. The c:929G>A variation has not been previously reported. We conclude
      that no pathogenic variations in ELOVL4 and PRPH2 were detected in the Chinese
      STGD patients. Our results imply that ABCA4 is more likely to be significant in
      Chinese STGD patients.

PMID- 22948569
TI  - Radiation and chest CT scans: are there problems? What should we do?

PMID- 22948570
TI  - The value of answering simple bronchoscopy questions with randomized clinical
      trials.

PMID- 22948571
TI  - Emerging bronchoscopic therapies for stage IV advanced emphysema.

PMID- 22948572
TI  - The homogeneous and robust clinical phenotype of severe lung injury.

PMID- 22948573
TI  - Scleroderma lung-associated cough: more than meets the eye?

PMID- 22948575
TI  - Critical care clinical trials: getting off the roller coaster.
AB  - Optimizing care in the ICU is an important goal. The heightened severity of
      illness in patients who are critically ill combined with the tremendous costs of
      critical care make the ICU an ideal target for improvement in outcomes and
      efficiency. Incorporation of evidence-based medicine into everyday practice is
      one method to optimize care; however, intensivists have struggled to define
      optimal practices because clinical trials in the ICU have yielded conflicting
      results. This article reviews examples where such conflicts have occurred and
      explores possible causes of these discrepant data as well as strategies to better
      use critical care clinical trials in the future.

PMID- 22948576
TI  - Long-term outcomes of pandemic 2009 influenza A(H1N1)-associated severe ARDS.
AB  - BACKGROUND: No data on long-term outcomes of survivors of 2009 influenza A(H1N1)
      (A[H1N1])-associated ARDS are available. The objective of this study was to
      compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to
      use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS
      severity surrogate. METHODS: Survivors of ARDS (12 with ECLA use vs 25 without,
      corresponding to 75% and 54% of the eligible patients for each group,
      respectively) selected from the Reseau Europeen de Ventilation Artificielle
      (REVA) registry had previously been healthy, with only pregnancy and/or moderate
      obesity (BMI <= 35 kg/m2) as known risk factors for A(H1N1) infection. Lung
      function and morphology, health-related quality of life (HRQoL), and psychologic
      impairment were evaluated. RESULTS: At 1 year post-ICU discharge for the ECLA and
      no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea,
      83% and 64% had returned to work, and 75% and 64% had decreased diffusion
      capacity across the blood-gas barrier, despite their near-normal and similar lung
      function test results. For both groups, exercise test results showed diminished
      but comparable exercise capacities, with similar alveolar-arterial oxygen
      gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL
      assessed by the 36-Item Short-Form Health Survey was poorer for both groups than
      for a sex- and age-matched general population group, but without between-group
      differences. ECLA and no-ECLA group patients, respectively, had symptoms of
      anxiety (50% and 56%) and depression (28% and 28%) and were at risk for
      posttraumatic stress disorder (41% and 44%). CONCLUSIONS: One year post-ICU
      discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung
      disabilities with diminished diffusion capacities across the blood-gas barrier,
      and most had psychologic impairment and poorer HRQoL than a sex- and age-matched
      general population group. ECLA and no-ECLA group patients had comparable
      outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01271842; URL:
      www.clinicaltrials.gov

PMID- 22948577
TI  - Mammalian target of rapamycin inhibitors in organ transplantation: an unkept
      promise.
AB  - The initial enthusiasm for the advent of a potentially nonnephrotoxic
      immunosuppressant has been muted by data unmasking nephrotoxicity of mammalian
      target of rapamycin inhibitors, including renal podocyte injury resulting in
      proteinuria. Adverse reactions, including anemia, thrombocytopenia,
      hyperlipidemia, and especially diabetogenesis, have limited its use to niche
      indications such as prevention or amelioration of malignancy in organ transplant.
      The class seems to be best used to address malignancy in organ allograft
      recipients and as a first-line therapy in lymphangioleiomyomatosis.

PMID- 22948578
TI  - Pulmonary rehabilitation: a review of the recent literature.
AB  - Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary,
      comprehensive intervention that can be integrated into the management of
      individuals with chronic lung disease. It aims to reduce symptoms, optimize
      function, increase participation in daily life, and reduce health-care resource
      utilization. In this review, we summarize the new developments in PR over the
      past 5 years. Issues related to patient assessment include a comparison of cycle-
      and walking-based measures of exercise capacity, the emergence of
      multidimensional indices, the refinement of the minimal clinically important
      difference, and the importance of assessing physical activity. Issues related to
      exercise training focus on strategies to optimize the training load. We also
      comment on the acquisition of self-management skills, balance training,
      optimizing access, and maintaining gains following completion of PR.

PMID- 22948579
TI  - Radiation and chest CT scan examinations: what do we know?
AB  - In the past 3 decades, the total number of CT scans performed has grown
      exponentially. In 2007, > 70 million CT scans were performed in the United
      States. CT scan studies of the chest comprise a large portion of the CT scans
      performed today because the technology has transformed the management of common
      chest diseases, including pulmonary embolism and coronary artery disease. As the
      number of studies performed yearly increases, a growing fraction of the
      population is exposed to low-dose ionizing radiation from CT scan. Data
      extrapolated from atomic bomb survivors and other populations exposed to low-dose
      ionizing radiation suggest that CT scan-associated radiation may increase an
      individual's lifetime risk of developing cancer. This finding, however, is not
      incontrovertible. Because this topic has recently attracted the attention of both
      the scientific community and the general public, it has become increasingly
      important for physicians to understand the cancer risk associated with CT scan
      and be capable of engaging in productive dialogue with patients. This article
      reviews the current literature on the public health debate surrounding CT scan
      and cancer risk, quantifies radiation doses associated with specific studies, and
      describes efforts to reduce population-wide CT scan-associated radiation
      exposure. CT scan examinations of the chest, including CT scan pulmonary and
      coronary angiography, high-resolution CT scan, low-dose lung cancer screening,
      and triple rule-out CT scan, are specifically considered.

PMID- 22948580
TI  - Relevance of latent TB infection in areas of high TB prevalence.
AB  - About one-third of the world population has latent TB infection (LTBI), the
      majority of which is distributed in 22 high-burden countries. Early diagnosis and
      treatment of active TB remains the top priority in resource-poor countries with
      high TB prevalence. Notwithstanding, because LTBI contributes significantly to
      the pool of active TB cases later on, its diagnosis and treatment is essential,
      especially in high-risk groups. The lack of a gold standard and several
      limitations of currently available tools, namely the tuberculin skin test and
      interferon-gamma release assays, are major constraints for LTBI diagnosis. In
      areas with high TB prevalence, interferon-gamma release assays have not shown
      superiority over the conventional tuberculin skin test and are yet to be
      systematically studied. Decisions regarding LTBI treatment with isoniazid
      preventive therapy should be made, keeping in mind the high prevalence of
      isoniazid resistance in these settings. Although efforts to shorten the LTBI
      treatment duration are encouraging, most trials have focused on adherence and
      toxicity. Future trials on short-duration regimens in high-burden settings should
      address drug efficacy issues as well. LTBI management, therefore, should comprise
      a targeted screening approach and individualization of LTBI treatment protocols.
      In addition, efforts should focus on airborne infection control measures in high
      burden countries. A high prevalence of drug-resistant TB, the HIV epidemic, and
      delays in the diagnosis of active TB cases are other major concerns in areas of
      high TB prevalence. There is ample space for further research in these countries,
      whose outcomes may strengthen future national guidelines.

PMID- 22948581
TI  - New coding in the International Classification of Diseases, Ninth Revision, for
      children's interstitial lung disease.
AB  - The term "children's interstitial lung disease" (chILD) refers to a heterogeneous
      group of rare and diffuse lung diseases associated with significant morbidity and
      mortality. These disorders include neuroendocrine cell hyperplasia of infancy,
      pulmonary interstitial glycogenosis, surfactant dysfunction mutations, and
      alveolar capillary dysplasia with misalignment of pulmonary veins. Diagnosis can
      be challenging, which may lead to a delay in recognition and treatment of these
      disorders. Recently, International Classifications of Diseases, Ninth Revision
      codes have been added for several of the chILD disorders. The purpose of this
      article is to give an overview of the chILD disorders and appropriate diagnostic
      coding.

PMID- 22948582
TI  - IgG4-related systemic disease presenting with lung entrapment and constrictive
      pericarditis.
AB  - We describe a 29-year-old woman who presented with chronic pleuropericarditis
      complicated by lung entrapment and constrictive pericarditis. Pleural biopsy
      performed during the decortication procedure revealed fibrinous pleuritis with
      lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient
      responded favorably to corticosteroid therapy with resolution of pleural effusion
      and constrictive physiology. To our knowledge, this is the first reported case of
      IgG4-related systemic disease manifesting as lung entrapment and constrictive
      pericarditis.

PMID- 22948583
TI  - Mycobacterial spindle cell pseudotumor of the lung.
AB  - Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion
      characterized by local proliferation of spindle-shaped histiocytes containing
      acid-fast mycobacteria. Most reported cases of MSP occur in the lymph nodes,
      skin, spleen, and brain in patients who are immunocompromised, particularly
      following solid organ transplant and in those with AIDS. This is a case report of
      a patient with AIDS who presented with cough, generalized weakness, and fatigue,
      who was found to have multilobar lung masses that were MSP, which to our
      knowledge has not yet been reported in the literature.

PMID- 22948584
TI  - Obesity and ARDS.
AB  - Obesity prevalence continues to increase globally, with figures exceeding 30% of
      some populations. Patients who are obese experience alterations in baseline
      pulmonary mechanics, including airflow obstruction, decreased lung volumes, and
      impaired gas exchange. These physiologic changes have implications in many
      diseases, including ARDS. The unique physiology of patients who are obese affects
      the presentation and pathophysiology of ARDS, and patients who are obese who have
      respiratory failure present specific management challenges. Although more study
      is forthcoming, ventilator strategies that focus on transpulmonary pressure as a
      measure of lung stress show promise in pilot studies. Given the increasing
      prevalence of obesity and the variable effects of obesity on respiratory
      mechanics and ARDS pathophysiology, we recommend an individualized approach to
      the management of the obese patient with ARDS.

PMID- 22948585
TI  - A 29-year-old woman with an intractable postoperative pleural effusion and
      pulmonary parenchymal opacification.

PMID- 22948586
TI  - A 36-year-old Haitian man with coma, acute kidney injury, lactic acidosis, and
      respiratory failure.

PMID- 22948587
TI  - A 66-year-old woman with dry cough and exertional dyspnea.

PMID- 22948592
TI  - Phentolamine for neurogenic pulmonary edema: bench to bedside progress.

PMID- 22948594
TI  - Bronchoscopy for refractory asthma.

PMID- 22948596
TI  - The journey from latent to active TB: no roadmaps as yet.

PMID- 22948598
TI  - Air-splinting maneuver during flexible fiber-optic bronchoscopy.

PMID- 22948599
TI  - From sleep-disordered breathing to increased left ventricular wall stress in
      heart failure.

PMID- 22948600
TI  - Optimal depth of tracheal intubation in severe scoliosis.

PMID- 22948601
TI  - Lipase-catalyzed preparation of diacylglycerol-enriched oil from high-acid rice
      bran oil in solvent-free system.
AB  - The ability of immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) to
      catalyze the reaction of high-acid rice bran oil (RBO) and monoglyceride (MG) for
      diacylglycerol-enriched rice bran oil (RBO-DG) preparation was investigated. The
      effects of substrate ratio, reaction temperature, time, and enzyme load on the
      respective content of free fatty acid (FFA) and DG in the final RBO-DG products
      was investigated. Enzyme screening on the reaction was also investigated.
      Response surface methodology (RSM) was used to optimize the effects of the
      reaction temperature (50-70  degrees C), the enzyme load (2-6 %; relative to the
      weight of total substrates), and the reaction time (4-8 h) on the respective
      content of FFA and DG. Validation of the RSM model was verified by the good
      agreement between the experimental and the predicted values. The optimum
      preparation conditions were as follows: MG/RBO, 0.25; temperature, 56  degrees C;
      enzyme load, 4.77 %; and reaction time, 5.75 h. Under the suggested conditions,
      the respective content of FFA and DG was 0.28 and 27.98 %, respectively. Repeated
      reaction tests indicated that Lipozyme RM IM could be used nine times under the
      optimum conditions with 90 % of its original catalytic activity still retained.

PMID- 22948602
TI  - Immobilization of Lecitase(r) Ultra onto a novel polystyrene DA-201 resin:
      characterization and biochemical properties.
AB  - A simple, rapid, and economic method of enzyme immobilization was developed for
      phospholipase Lecitase(r) ultra (LU) via interfacial adsorption. The effect of
      nature of the polystyrene supports and the kinetic behavior and stability of
      immobilized lecitase(r) ultra (IM-LU) were evaluated. Six macroporous resins (AB
      8, X-5, DA-201, NKA-9, D101, D4006) and two anion resins (D318 and D201) were
      studied as the supports. DA-201 resin was selected because of its best
      immobilization effect for LU. Immobilization conditions were investigated,
      including immobilization time, pH, and enzyme concentration. IM-LU with a lipase
      activity of 1,652.4 +/- 8.6 U/g was obtained. The adsorption process was modeled
      by Langmuir and Freundlich equations, and the experimental data were better fit
      for the former one. The kinetic constant (K (m)) values were found to be 192.7 +/
      2.2 mM for the free LU and 249.3 +/- 5.4 mM for the IM-LU, respectively. The V
      (max) value of free LU (169.5 +/- 4.3 mM/min) was higher than that of the IM-LU
      (53.8 +/- 1.5 mM/min). Combined strategies of scanning electron micrograph,
      thermogravimetric analysis, and Fourier transform infrared (FTIR) spectroscopy
      were employed to characterize the IM-LU. FTIR spectroscopy showed that the
      secondary conformation of the enzyme had changed after immobilization, through
      which a decrease of alpha-helix content and an increase of beta-sheet content
      were observed. The IM-LU possessed an improved thermal stability as well as metal
      ionic tolerance when compared with its free form. The reusability of IM-LU was
      also evaluated through catalyzing esterification reaction between oleic acid and
      glycerol. It exhibited approximately 70 % of relative esterification efficiency
      after six successive cycles. This immobilized enzyme on hydrophobic support may
      well be used for the synthesis of structural lipids in lipid area.

PMID- 22948603
TI  - Visible-light-induced bactericidal activity of vanadium-pentoxide (V2O5)-loaded
      TiO2 nanoparticles.
AB  - The bactericidal activity of TiO(2) nanoparticles under visible light is very
      important in regards to its practical applications. In this paper, we synthesized
      vanadium-pentoxide-loaded TiO(2) nanoparticles (V(2)O(5)-TiO(2)) using a chemical
      vapor condensation method, followed by the impregnation method, and characterized
      its physicochemical properties through X-ray diffraction patterning, X-ray
      photoelectron spectroscopy analysis, Raman spectra analysis, and Fourier
      transform infrared analysis. In addition, the antibacterial activity of V(2)O(5)
      TiO(2) nanoparticles against E. coli was evaluated and compared with pure TiO(2)
      nanoparticles. In these experiments, the population of E. coli was shown to be
      significantly reduced by V(2)O(5)-TiO(2) nanoparticles under illumination with
      fluorescent light, whereas pure TiO(2) nanoparticles showed about 3.3-fold lower
      antibacterial activity than the V(2)O(5)-TiO(2) nanoparticles. This result was
      most likely due to the change in surface conditions of the TiO(2) nanoparticles,
      which was due to the loading of vanadium pentoxide on the TiO(2) nanoparticles.
      Furthermore, both photocatalysts showed similar antibacterial activity under UV-A
      (352 nm) irradiation.

PMID- 22948604
TI  - Synthesis and biological evaluation of a novel series of chalcones incorporated
      pyrazole moiety as anticancer and antimicrobial agents.
AB  - A newly synthesized series of chalcone derivatives containing pyrazole rings were
      synthesized and evaluated for their cytotoxic activities in vitro against several
      human cancer cell lines. Most of the prepared compounds showed potential
      cytotoxicity against human breast cancer cell lines MCF-7, HEPG-2, and HCT-116.
      Also the compounds were evaluated as antimicrobial agents. The three compounds 3,
      4, and 5 were proved to be better anticancer agents than the positive standard
      doxorubicin with IC50 values (4.7, 4.4, and 3.9 MUg/ml) against the same human
      cancer cell lines, whereas compounds 5 and 6 showed the most active antimicrobial
      compounds in comparison to the other chalcones.

PMID- 22948605
TI  - Identification of new dominant-negative mutants of anthrax protective antigen
      using directed evolution.
AB  - The anthrax toxin is composed of three proteins: protective antigen (PA), lethal
      factor (LF), and edema toxin (EF). The PA moiety carries EF and LF into the
      cytosol of mammalian cells via a mechanism that depends on the oligomerization of
      PA and transmembrane pore formation by the PA oligomer. Certain mutants of PA,
      termed dominant-negative (DN) mutants, can co-oligomerize with wild-type PA and
      disrupt the translocation ability of the pore. Here, we constructed a PA mutant
      library by introducing random mutations into domain II of PA and screened three
      new DN mutants of PA: V377E, T380S, and I432C. All the mutants inhibited the
      anthrax toxin action against sensitive cells. V377E had the strongest inhibitory
      effect and was further confirmed to be able to protect mice against a challenge
      with anthrax lethal toxin. Furthermore, we functionally characterized these
      mutants. The result showed that these mutations did not impair proteolytic
      activation or oligomer formation of PA, but impeded the prepore-pore conversion
      of the oligomer. These DN mutants of PA identified in our study may provide
      valuable information for elucidating the structure-function relationship of PA
      and for designing therapeutics for anthrax treatment.

PMID- 22948606
TI  - Biodecolorization of azo dye Remazol orange by Pseudomonas aeruginosa BCH and
      toxicity (oxidative stress) reduction in Allium cepa root cells.
AB  - In this report a textile azo dye Remazol orange was degraded and detoxified by
      bacterium Pseudomonas aeruginosa BCH in plain distilled water. This bacterial
      decolorization performance was found to be pH and temperature dependent with
      maximum decolorization observed at pH 8 and temperature 30  degrees C. Bacterium
      tolerated higher dye concentrations up to 400 mg l(-1). Effect of initial cell
      mass showed that higher cell mass concentration can accelerate decolorization
      process with maximum of 92 % decolorization observed at 2.5 g l(-1) cell mass
      within 6.5 h. Effect of various metal ions showed Mn has inducing effect whereas
      Zn strongly inhibited the decolorization process at 5 mM concentration. Analysis
      of biodegradation products carried out with UV-vis spectroscopy, HPTLC and FTIR
      confirmed the decolorization and degradation of Remazol orange. Possible route
      for the degradation of dye was proposed based on GC-MS analysis. During
      toxicological scrutiny in Allium cepa root cells, induction in the activities of
      superoxide dismutase (SOD), guaiacol peroxidase (GPX) and inhibition of catalase
      (CAT) along with raised levels of lipid peroxidation and protein oxidation in dye
      treated samples were detected which conclusively indicated the generation of
      oxidative stress. Less toxic nature of the dye degraded products was observed
      after bacterial treatment.

PMID- 22948608
TI  - Facile synthesis of MoS2@CMK-3 nanocomposite as an improved anode material for
      lithium-ion batteries.
AB  - MoS(2)@CMK-3 nanocomposite consisting of confined nanosized MoS(2) in CMK-3
      carbon matrix exhibits much improved cycling performance and rate capability due
      to the enlarged interlayer distance and favorable conductivity.

PMID- 22948607
TI  - RANKL enhances macrophage paracrine pro-calcific activity in high phosphate
      treated smooth muscle cells: dependence on IL-6 and TNF-alpha.
AB  - BACKGROUND: Vascular calcification is highly correlated with cardiovascular
      disease (CVD) morbidity and mortality, and it is associated with inflammation.
      Receptor activator of NF-KB ligand (RANKL) inhibition in vivo has been shown to
      reduce vascular calcification in a mouse model of atherosclerosis. Therefore, we
      tested the hypothesis that RANKL regulates smooth muscle cell (SMC) calcification
      by modulating macrophage production of pro-calcific cytokines. METHODS: We used a
      bone marrow-derived macrophage (BMDM)/SMC co-culture system and examined the
      effects of RANKL on BMDM activation and SMC matrix calcification. RESULTS:
      Treatment with RANKL alone did not stimulate SMC calcification induced by
      elevated phosphate. BMDMs differentiated with macrophage colony-stimulating
      factor and placed in co-culture with SMCs increased phosphate-induced SMC
      calcification. RANKL added to the BMDM/SMC co-cultures further enhanced SMC
      calcification. Treatment of BMDMs with RANKL resulted in increased expression of
      IL-6 and TNF-alpha. Thus, increased expression of these pro-calcific cytokines in
      macrophages may mediate RANKL-induced SMC calcification in a paracrine fashion.
      Addition of neutralizing IL-6 and TNF-alpha antibodies together with RANKL
      treatment significantly reduced the RANKL induction of SMC calcification.
      CONCLUSION: RANKL activation of pro-inflammatory and pro-calcific pathways in
      macrophages may contribute to vascular calcification and inflammation.

PMID- 22948610
TI  - Incomptines C and D, two heliangolides from Decachaeta incompta and their
      antiprotozoal activity.
AB  - Two new heliangolides, incomptines C (3) and D (4), were isolated from the leaves
      of Decachaeta incompta. The structures were established by spectroscopic methods
      and confirmed by X-ray crystallography. The antiprotozoal activity of incomptines
      C and D was evaluated. Additionally, the chromatographic profile of the leaves
      and roots extracts were compared to identify incomptines A-D (1-4) in each
      extract.

PMID- 22948611
TI  - Pyrone and unusually furanone-substituted flavones from the leaves of Hoslundia
      opposita.
AB  - Two new unusual 6-furanoflavones, hoslunfuranine (5) and 5-O-methylhoslunfuranine
      (6), were isolated from the leaves of Hoslundia opposita Vahl.. Four known
      methylpyranoflavonic analogues [hosloppin (1), hoslundin (2), 5-O-methylhoslundin
      (3), oppositin (4)], all specific of the species, were also obtained. Their
      structures were established on the basis of their spectroscopic data. In vitro
      cytotoxic, trypanocidal, and leishmanicidal activities of compounds 1 and 3 to 6
      were evaluated. Compounds 4 and 6 exhibited leishmanicidal potential in the
      micromolar range.

PMID- 22948612
TI  - Five new 3,4-seco-lanostane-type triterpenoids with antiproliferative activity in
      human leukemia cells isolated from the roots of Kadsura coccinea.
AB  - Five new 3,4-seco-lanostane-type triterpenoids, seco-coccinic acids G-K (1-5),
      and a known compound, seco-coccinic F, were isolated from the roots of Kadsura
      coccinea (Lem.) A. C. Sm. Their structures were elucidated by spectroscopic
      methods, including 2D-NMR and HR-MS techniques. The cell growth inhibitory
      effects of these compounds were assayed in human leukemia HL-60 cells, and it was
      found that 1, 5, and 6 showed antiproliferative effects with GI50 values of 28.4,
      15.2, and 16.6 uM, respectively.

PMID- 22948613
TI  - Environmental sex determination mechanisms in reptiles.
AB  - Temperature-dependent sex determination (TSD) was first discovered in reptiles.
      Since then, a great diversity of sex-determining responses to temperature has
      been reported. Higher temperatures can produce either males or females, and the
      temperature ranges and lengths of exposure that influence TSD are remarkably
      variable among species. In addition, transitory gene regulatory networks leading
      to gonadal TSD have evolved. Although most genes involved in gonadal development
      are conserved in vertebrates, including TSD species, temporal and spatial gene
      expression patterns vary among species. Despite variation in TSD pattern and gene
      expression heterochrony, the structural framework, the medullary cords, and
      cortex of the bipotential gonad have been strongly conserved. Aromatase (CYP19),
      which regulates gonadal estrogen levels, is proposed to be the main target of a
      putative thermosensitive factor for TSD. However, manipulation of estrogen levels
      rarely mimics the precise timing of temperature effects on expression of gonadal
      genes, as occurs with TSD. Estrogen levels may influence sex determination or
      gonad differentiation depending on the species. Furthermore, the process leading
      to sex determination under the influence of temperature poses problems that are
      not encountered by species with genetic sex determination. Yolk steroids of
      maternal origin and steroids produced by the embryonic nervous system should also
      be considered as sources of hormones that may play a role in TSD.

PMID- 22948614
TI  - Life satisfaction in older women in Latvia and Sweden-relations to standard of
      living, aspects of health and coping behaviour.
AB  - To study and compare associations between life satisfaction and standard of
      living, health, and coping behaviour in older single-living women in two
      countries with different political, economical and cultural situations: Latvia
      and Sweden. Cross sectional data included 260 Latvian and 288 Swedish women, aged
      75-84 and 80-89, from the ENABLE-AGE Survey Study. Life satisfaction was assessed
      by the question: All in all, how satisfied are you with your life? Standard of
      living was assessed by economic and housing conditions, and health by perceived
      and objective health and activities in daily living. Three factors, Fight,
      Helplessness, and Distraction, were obtained from the Coping Patterns Schedule.
      Correlations between Life satisfaction and standard of living, health, and coping
      were calculated. The variance in Life satisfaction explained by these variables
      was obtained in each sample by ordinal regression models. Life satisfaction was
      significantly lower in the Latvian sample than in the Swedish. Standard of living
      was lower and health poorer in the younger Latvian sample than in the Swedish,
      but more of the variance in Life satisfaction was explained in the Latvian sample
      by standard of living (18% vs 2%) and less by health (6% vs 15%). Coping factors
      explained 29% of the variation in Life satisfaction in the Latvian sample as
      opposed to 15% in the Swedish. For single-living older women low standard of
      living seems to be a more serious obstacle than poor health, making it difficult
      to obtain a reasonable life satisfaction.

PMID- 22948615
TI  - Mortality in the TRACER and ATLAS ACS 2 trials: two more reasons to audit vital
      records in PLATO.
AB  - CONTEXT: Extreme rates of vascular and all-cause mortality, especially in the
      clopidogrel arm of the PLATO (PLATelet Inhibition and Clinical Outcomes) trial,
      raise concerns of data accuracy and call for independent verification of vital
      records in the national death registries. Two recently completed acute coronary
      syndrome (ACS) trials, TRACER and ATLAS ACS 2 (Thrombin Receptor Antagonist for
      Clinical Event Reduction in ACS and Anti-Xa Therapy to Lower Cardiovascular
      Events in Addition to Standard Therapy in Subjects with ACS-Thrombolysis in
      Myocardial Infarction), provide a valuable opportunity to match mortality numbers
      among 3 similar studies. OBJECTIVE: To compare the rates of vascular and all
      cause mortality in the PLATO, TRACER and ATLAS ACS 2 trials. RESULTS: Despite a
      shorter mean follow-up (277 days) for the PLATO trial than for the TRACER (502
      days) or ATLAS ACS 2 (393 days) trials, both vascular (5.1%) and all-cause (5.9%)
      mortality in PLATO were higher than in the TRACER (3.2 and 4.9%) or ATLAS ACS 2
      (4.1 and 4.5%) control arms, respectively. Adjusting for follow-up duration,
      rates of vascular (0.0184/day), or all-cause (0.0213/day) mortality in PLATO
      differ importantly from daily death rates in TRACER (0.0063 and 0.0097) and ATLAS
      ACS 2 (0.0104 and 0.0115), suggesting that the risk of death in the control PLATO
      arm was approximately double that of the other trials. The mismatch is
      particularly striking considering that ATLAS ACS 2 enrolled more STEMI (ST
      segment elevation in myocardial infarction) patients (50.9%) than PLATO (38.0%).
      CONCLUSIONS: Both overall and follow-up duration-adjusted mortality rates in
      PLATO far exceeded the risk of death observed in the two recent ACS trials. The
      background STEMI rates are not likely to be responsible for the PLATO mortality
      paradox. These data provide an additional reason to request an independent audit
      of the deceased PLATO clopidogrel cohort.

PMID- 22948616
TI  - No basophil infiltration in alopecia areata irrespective of the intensity of
      eosinophil infiltration.

PMID- 22948617
TI  - Celebrating the 80th anniversary of the Shanghai Institute of Materia Medica,
      Chinese Academy of Sciences (SIMM).

PMID- 22948618
TI  - Comparison of pediatric and adult nasal fractures.
AB  - Nasal fractures are the most common facial fracture in children and adults.
      Generally, it is believed that reduction of pediatric nasal fracture is more
      difficult and should be performed earlier compared with that of adult nasal
      fracture. However, there has been no article to prove this theory. We
      investigated 423 patients with acute nasal fractures requiring surgery and
      divided them into the following 2 groups: patients 12 years and younger
      (pediatric group) and patients 13 years and older (adult group). We then compared
      these patients in various aspects. There were no significant differences in the
      cause of fracture or postoperative conditions. Only the type of fracture and the
      anesthesia were different between these 2 groups. In the pediatric group, the
      interval between injury and surgery was arbitrarily divided into 2 groups, but
      there was no significant difference between these groups in the postoperative
      conditions. Some reports recommended that pediatric nasal fractures should be
      reduced within 3 to 5 days, but it cannot be proven. In conclusion, it is not
      necessary to distinguish treatment of pediatric nasal fracture from that of adult
      nasal fracture.

PMID- 22948619
TI  - Grafting of large mandibular advancement with a collagen-coated bovine bone (Bio
      Oss Collagen) in orthognathic surgery.
AB  - Current principles for correction of dentoskeletal deformities ask to satisfy
      different treatment goals, making large mandibular advancements a common practice
      in orthognathic surgery. A main consequence of significant mandibular movements
      is the potential for unfavorable bone healing of osteotomy sites after
      traditional sagittal split procedures. This drawback, which mainly occurs at the
      level of inferior mandibular borders, can affect the stability and support of
      overlying soft tissues. Whereas the role of bone grafting for upper jaw defects
      after Le Fort I osteotomy is well addressed in the Literature, until now, just a
      few articles discussed the potential for grafting of mandibular osteotomy sites.
      The aim of this study is to evaluate the healing of mandibular bone defects
      because of large advancement (>8 mm) after sagittal spit procedures. In 20
      patients treated for correction of class II dentoskeletal deformities, mandibular
      osteotomies defects have been grafted with a collagen-coated bovine bone
      substitute. Clinical, radiological, and histological evaluation of grafted sites
      showed a good healing of grafted area both in terms of recontouring of inferior
      mandibular borders and in terms of quality of newly formed bone. This confirms
      how this procedure could help to avoid the drawbacks related to significant
      mandibular advancement.

PMID- 22948620
TI  - Alar web in cleft lip nose deformity:  study in adult unilateral clefts.
AB  - BACKGROUND: The correction of alar webbing in unilateral cleft lip nose deformity
      is challenging because of progressive distortions in the alar web region during
      the period of growth. Alar webbing is a persistent universal deformity in both
      the primary and secondary cleft lip noses. The purpose of this article is to
      study the alar web deformity in adult patients with unilateral cleft lip noses.
      METHODS: Twenty-five patients aged 13 years and older presenting with unilateral
      cleft nasal deformity were included. Preoperative and postoperative measurements
      of the nose, along with detailed intraoperative recording of the deformed
      anatomy, were done. Preoperative magnetic resonance imaging was also done in
      selected cases. Transcolumellar open rhinoplasty was performed in all the cases,
      and nasal septal straightening with centralization was done. Cleft alar base
      augmentation was done using bone graft to restore symmetry of the nasal tripod.
      Both the cleft and noncleft alar cartilages were extensively mobilized from the
      skin and mucosal sides. The overgrown and caudally slumped cleft-side alar
      cartilage was resected caudally and was then resuspended in a symmetrical
      position with the noncleft alar cartilage. A midline-strut septal cartilage
      extension graft was used to restore the tip aesthetics. The skin overlying the
      alar web was in-rolled after semilunar cartilage resection, and skin excision was
      also done to restore symmetry with the opposite vestibule. The remaining
      secondary cleft nasal and lip deformities were corrected depending upon the
      specific presenting pathologic abnormality. RESULTS: The cleft alar cartilage was
      found to be caudally displaced in all the cases. The caudal border of the lateral
      crus was prolapsing in the cavity of the vestibule on the superomedial aspect and
      was tenting the skin in the area of the weak triangle, producing the
      characteristic alar web deformity. In the study group, the maximum width of the
      cleft alar cartilage at the level of the lateral crus was increased by
      approximately 4 mm when compared with the noncleft alar cartilage. The before-
      and after-rhinoplasty surgery results were objectively assessed using a patient,
      surgeon, and independent observer survey. The cosmetic result of the nasal tip
      complex was found to be very good and good (90%), satisfactory (5%), and poor
      (5%) in patients. CONCLUSIONS: The alar web in unilateral cleft lip nose
      deformity is the result of caudal overgrowth and migration of the alar cartilage.
      The caudal edge of the prolapsed lateral crus overhangs the cleft-side nasal
      aperture on its superomedial aspect, producing this deformity. Satisfactory
      correction of this deformity should envisage caudal resection and repositioning
      of the dislocated alar cartilage along with caudal resection of the lateral crus
      with in-rolling of the skin after resection to achieve symmetric results in
      unilateral cleft lip rhinoplasty.

PMID- 22948621
TI  - Three-dimensional computed tomographic analysis of the maxilla in unilateral
      cleft lip and palate:  implications for rhinoplasty.
AB  - BACKGROUND: The cleft lip nose is a complex 3-dimensional (3D) midfacial soft
      tissue and bony deformity. The contribution of maxillary hypoplasia to the
      etiology of this deformity has often been implicated for the suboptimal results
      of surgical treatment. The dimensions of the maxilla in unilateral cleft lip and
      palate (UCLP) have not been studied especially in relation to the volumetric and
      other asymmetries on the either side in unilateral clefts. The purpose of this
      article is to assess the relevant maxillary parameters of length, width, height,
      depth, and volume in patients with UCLP and compare the parameters of the cleft
      and noncleft sides. METHODS: Fifteen patients with UCLP were treated by a
      standard protocol by a single surgeon and orthodontist. The measurements of
      maxilla were taken using a combination of axial, coronal, lateral, and 3D
      reconstructed images. The volume of each maxilla was calculated on 3D
      reconstructions using the technique of manual segmentation, which allowed
      complete reconstruction of the right and left maxilla individually. RESULTS: In
      general, the cleft maxillary length, width, height, depth, and volume have been
      found to be reduced when compared with the normal sides with significant P values
      (Wilcoxon signed rank test Z, P < 0.001). CONCLUSIONS: The study demonstrates the
      anatomy of the maxillary asymmetry existing in UCLP and underlines the importance
      of correcting the bony deficiency by appropriate techniques to harmonize the
      results of rhinoplasty in unilateral cleft lip nose deformity. Augmentation of
      the deficient maxilla by specific contoured bone grafts allows restoration of the
      symmetry of the nasal platform in unilateral cleft lip nose deformity.

PMID- 22948622
TI  - Embryonic fate map of first pharyngeal arch structures in the sox10: kaede
      zebrafish transgenic model.
AB  - Cranial neural crest cells follow stereotypic patterns of migration to form
      craniofacial structures. The zebrafish is a powerful vertebrate genetic model
      where transgenics with reporter proteins under the transcriptional regulation of
      lineage-specific promoters can be generated. Numerous studies demonstrate that
      the zebrafish ethmoid plate is embryologically analogous to the mammalian palate.
      A fate map correlating embryonic cranial neural crest to defined jaw structures
      would provide a useful context for the morphogenetic analysis of craniofacial
      development. To that end, the sox10:kaede transgenic was generated, where sox10
      provides lineage restriction to the neural crest. Specific regions of neural
      crest were labeled at the 10-somite stage by photoconversion of the kaede
      reporter protein. Lineage analysis was carried out during pharyngeal development
      in wild-type animals, after miR140 injection, and after estradiol treatment. At
      the 10-somite stage, cranial neural crest cells anterior of the eye contributed
      to the median ethmoid plate, whereas cells medial to the eye formed the lateral
      ethmoid plate and trabeculae and a posterior population formed the mandible. miR
      140 overexpression and estradiol inhibition of Hedgehog signaling resulted in
      cleft development, with failed migration of the anterior cell population to form
      the median ethmoid plate. The sox10:kaede transgenic line provides a useful tool
      for neural crest lineage analysis. These studies illustrate the advantages of the
      zebrafish model for application in morphogenetic studies of vertebrate
      craniofacial development.

PMID- 22948623
TI  - "Bibloc advancement" with a combination of internal and external distracters.
AB  - Frontofacial monobloc advancement is one of the most rewarding techniques for
      correcting aesthetic and functional problems of patients with severe craniofacial
      synostosis, which can advance the upper and middle third of the face
      simultaneously. Application of gradual distraction technique has been reported to
      reduce notorious risks after a frontofacial monobloc advancement. The so-called
      "bibloc advancement" is a derivative of the frontofacial monobloc advancement.
      "Facial bloc" is horizontally divided into 2 different components: fronto-orbital
      component and maxillozygomatic component. From a different angle, it can be
      described as a combination of fronto-orbital advancement and Le Fort III
      advancement. Two pairs of distracters (1 internal for the supraorbital area and 1
      external for the maxillozygomatic area with a pair of cross-facial pinning) were
      applied after the so-called bibloc osteotomy. Advancement of the upper and middle
      third of the face was done individually. This technique can be a good option for
      treating infants with severe syndromic craniofacial synostosis.

PMID- 22948624
TI  - Preliminary application of virtual simulation and reposition template for
      zygomatico-orbitomaxillary complex fracture.
AB  - This report introduced and evaluated our computer-assisted surgical method in the
      treatment of complex maxillofacial fractures. One patient with zygomatico
      orbitomaxillary complex fracture underwent computed tomography to obtain DICOM
      data. Three-dimensional reconstruction and virtual surgical planning were carried
      out in the software MIMICS 10.01. Three reposition templates and 1 skull model
      were manufactured in our three-dimensional rapid prototyping machine.
      Reconstruction surgery was carried out according to the preoperative planning and
      with the guide of reposition templates. At 3-month follow-up, the treatment
      outcome was consistent with preoperative planning exactly, and the patient
      expressed high satisfaction with the surgery. Combination of reposition templates
      and rapid prototyping method demonstrated great practical value in complex
      maxillofacial fracture surgery.

PMID- 22948625
TI  - Reconstruction of anterior scalp defect with V-Y advancement flap pedicled on the
      temporal fascia superficialis.
AB  - Reconstruction of scalp defect can call upon several surgical techniques. Direct
      joining is used whenever possible, but because of the low laxity of the scalp,
      other approaches are often required. Several types of autoclosing flaps of the
      scalp have been described in the literature. In this article, we report the
      advantages of the island flap pedicled on the superficial temporal fascia, as
      described by Onishi (2005) in a case report for the reconstruction of an anterior
      scalp defect.

PMID- 22948626
TI  - Incidence of major and minor brain injuries in facial fractures.
AB  - BACKGROUND: Facial fractures can be associated with brain and cervical spine
      injuries because impact forces are transmitted through the head and neck.
      Although major brain injury is commonly recognized in these patients, incidence
      of minor brain injury is not well-known, despite potential morbidity and
      mortality. OBJECTIVES: This prospective study aimed to determine the incidence of
      both major and minor brain injuries in 100 patients presenting to a craniofacial
      surgery service with facial fractures and to identify characteristics associated
      with brain injury. METHODS: Data were collected for a 9-month period by a
      craniofacial surgeon at a level I trauma center. A questionnaire and checklist
      were designed to capture information about major and minor brain injury in
      patients with facial fractures. Assessments were completed in the outpatient
      clinic, emergency department, hospital ward, or intensive care unit during the
      first patient encounters. RESULTS: The average age of patients was 34 years; 79%
      were male. Time between injury and assessment ranged from less than a few hours
      to 4 months. Incidence of brain injury was 67% overall: 29% with major brain
      injury and 38% with minor injury. Major brain injury was commonly diagnosed early
      in the emergency department or intensive care unit. Conversely, minor brain
      injury tended to be diagnosed late in the clinic. Patient age, mechanism of
      injury, and type of facial fracture predicted brain injuries overall, but
      mechanism of injury was the sole predictor of minor brain injury. CONCLUSIONS:
      Facial fractures are often associated with brain injury. A high level of
      suspicion is warranted for minor traumatic brain injuries.

PMID- 22948627
TI  - Radiologic and long-term clinical outcome from treatment of isolated medial
      orbital wall blowout fractures.
AB  - Blowout fractures in the medial orbital wall may lead to enophthalmos, ocular
      dysmotility, and diplopia. Ten consecutive patients with unilateral, isolated
      fractures of the medial orbital wall were retrospectively studied. The radiologic
      accuracy of the medial orbital wall reconstructions and the long-term clinical
      outcomes were assessed. All cases were treated through a bicoronal approach and
      by use of porous polyethylene-titanium implants. The total fracture area and the
      orbital volume increase from the blowout were measured on computed tomographic
      scans. Next, we evaluated the reconstruction in the posterior part of the medial
      wall. This was done by calculating the ratio between the defect area and the
      implant area located behind the anterior ethmoidal canal. The patients were
      examined at least 1 year after the operation, and the rates of enophthalmos and
      diplopia were evaluated. The mean fracture defect area was 2.45 cm2 (range, 0.41
      4.16 cm2), and the mean volume increase from the blowout fractures was 1.82 cm3
      (range, 0.53-2.76 cm3). The orbital volume was accurately restored in all
      patients. However, the ratio of implant to defect area behind the anterior
      ethmoidal canal ranged from 0% to 100% (mean, 47.3%). None of the patients had
      enophthalmos or diplopia at the long-term follow-up. The results confirm that
      restoration of orbital volume is important to prevent postoperative enophthalmos
      in isolated medial orbital blowout fractures. Complete reconstruction of the most
      posterior part of the medial orbital wall seems to be of lesser importance.

PMID- 22948628
TI  - Pentagonal hinge osteotomy for reduction of the wide nasal base of Asians.
AB  - We designed a pentagonal hinge osteotomy procedure for reduction of the wide
      nasal base of Asians. Minimal dissection was performed on the nasal bone and
      frontal process of the maxilla. Following determination of the desired width of
      the nose, partial-thickness osteotomy was performed first, using a hand saw at
      the midlevel from the midline to the lateral osteotomy line. Then, using a
      guarded osteotome, lateral osteotomy was performed at the piriform aperture.
      Thus, the lateral border of the triangle was a full-thickness cut, and the medial
      border was a partial-thickness cut. With digital pressure, lateral parts of
      triangular segments were moved medially, leaving the medial hinge intact, causing
      a greenstick fracture. Thereafter, the nasal framework became a pentagonal
      structure, and the broad nasal base was narrowed. Seven patients (4 males and 3
      females; mean age, 24.6 years) underwent surgery. Average follow-up period was
      23.8 months. No occurrence of mucosal injury, infection, step deformity, or
      airway collapse was observed. It is thought that pentagonal hinge osteotomy might
      be useful for reduction of the wide nasal base of Asians.

PMID- 22948629
TI  - Cranial vault remodeling in microcephalic osteodysplastic primordial dwarfism
      type II and craniosynostosis.
AB  - This is a survey of the long-term result after various surgical treatments in a
      child with microcephalic osteodysplastic primordial dwarfism type II (MOPD II)
      and craniosynostosis. We report a 17-year-old patient with MOPD II but some
      unusual clinical signs including bilateral knee dislocation, a misplaced upper
      lobe bronchus, and hypoplasia of the anterior corpus callosum. Because of
      premature fusion of several cranial sutures, the child developed signs of
      increased intracranial pressure with somnolence and papilledema. Cranial vault
      remodeling with fronto-orbital advancement was performed twice at the age of 16
      and 21 months to open the abnormally closed suture, increase the intracranial
      volume, and relieve the elevated intracranial pressure. Following this procedure,
      the child's neurologic situation recovered significantly. Surgical procedure of
      fronto-orbital advancement and the performed reoperation in our patient were safe
      with no major complications intraoperatively and postoperatively with good
      functional and satisfying aesthetic outcomes in the long-term follow-up,
      expressed by the patient, his parents, and the surgeons.

PMID- 22948630
TI  - Electromyographic study in patients with surgically treated facial fractures.
AB  - This study, using surface electromyography, analyzed the activity of the masseter
      muscles of 30 patients with facial bone fractures that were surgically treated.
      Evaluations were made before surgery and in the 7th, 30th, and 60th days after
      surgery. The value of each measure and the average of 3 maximum voluntary
      isometric contractions lasting 5 seconds each were registered, and statistical
      analyses were performed. Patients had a mean age of 31 years and an average of
      1.33 fractures. They were grouped according to the type of fracture as follows:
      mandibular (50%), zygomatic complex (33%), maxilla (10%), and associated
      fractures (6.7%). There was a lower masseter activity in the preoperative period,
      when compared with normal values in all groups of fractures. There was a sharp
      drop in the masseter activity in the postoperative period of 7 days, and all
      groups showed recovery of activity in 60 days but still below the normal value
      referenced in the literature. The mean values of the masseter activity, in
      descending order, were from the zygomatic complex, mandibular, maxillary, and
      associated fractures. The unilateral mandibular fractures showed higher values
      than the bilateral fractures in most of the evaluations. There was a highly
      significant difference in the comparison of the evolution of the masseter
      activity on both sides, for mandibular and zygomatic complex fractures, and the
      pairwise comparison showed significant difference between most groups. It was
      concluded that facial fractures and surgical procedures had negative effects in
      the muscle activity as observed using electromyography.

PMID- 22948631
TI  - Clinical outcome of cranioplasty with high-density porous polyethylene.
AB  - BACKGROUND: High-density porous polyethylene (Medpor) has long been used in
      cranioplasty and is still one of the best materials for calvarial reconstruction.
      Calvarial defects can be effectively reconstructed with fewer complications by
      using Medpor. This article reports our study on the use of Medpor in
      reconstructing calvarial defects. METHODS: Twenty-three patients who underwent
      cranioplasty from 1999 to 2011 were included in this study. In all patients,
      Medpor was used for calvarial defect reconstruction, and all were followed up for
      at least 6 months. RESULTS: Most patients were satisfied with the reconstructive
      outcome. Only 1 patient had an infection and 1 had transient extradural seroma.
      All complications occurred within 2 years, and no new complications were found
      during the long-term follow-up. CONCLUSIONS: Using Medpor in cranioplasty is an
      effective method for reconstructing calvarial defects.

PMID- 22948633
TI  - Total scalp replantation salvaged by changing the recipient vein.
AB  - Successful replantation of the avulsed scalp has been reported by a number of
      authors, and there seems almost no doubt that each single superficial temporal
      artery and vein is enough to feed and drain the whole scalp if the amputee is not
      severely torn. As the venous problem is the most common cause of failure, efforts
      have been made to anastomose reliable veins for drainage. We report a case of
      total scalp avulsion that was, at first, fed and drained by a superficial
      temporal artery and an ipsilateral supraorbital vein. Congestion progressed
      slowly, and exploration revealed patent venous anastomosis without apparent
      thrombosis. Congestion was relieved when the recipient was changed to superficial
      temporal vein using a vein graft, leading to complete survival of the scalp. We
      propose the importance of the capacity of recipient vein, in addition to the
      anastomotic patency, for successful replantation of the whole scalp. We assume
      that the capacity of a small caliber recipient vein may be limited even in full
      dilatation, and the importance of the competent recipient vein should not be
      overlooked in a large amputee replantation or a large free flap surgery.

PMID- 22948632
TI  - Compression and stretching in Graves orbitopathy: emergency orbital decompression
      techniques.
AB  - Visual loss from orbital compression and stretching of the optic nerve is an
      infrequent but well-recognized cause of dysthyroid optic neuropathy, occurring in
      less than 5% of thyroid eye disease cases. Another important but less recognized
      cause of vision loss due to thyroid-associated optic neuropathy is protracted
      stretching of the optic nerve. Of the reported cases of compression and stretch
      optic neuropathy, none have documented the rate of vision loss due to continuous
      stretching of the optic nerve.

PMID- 22948634
TI  - Bone healing in critical-size defects treated with immediate transplant of
      fragmented autogenous white adipose tissue.
AB  - This study analyzed the influence of fragmented autogenous white subcutaneous
      adipose tissue (WSAT) on bone healing in critical-size defects created in rabbit
      calvaria. A 15-mm diameter defect was created in the calvaria of 42 rabbits,
      which were treated with 86 mm3 WSAT grafts or filled only with blood clots
      (control). Animals were euthanized at 7, 15, and 40 days postsurgery (n = 7), and
      the data were analyzed using histomorphometry and immunohistochemistry using the
      anti-CD34 and bone morphogenetic protein-2 (BMP2) antibodies. The calvaria
      treated with only blood clots demonstrated positivity to CD34 concentrated in
      endothelial cells, whereas the BMP2 were restricted to the borders of the
      defects. In contrast, the group treated with WSAT revealed fatty cells exhibiting
      positivity to BMP2 both in membrane and cytoplasm and intense quantities of
      stromal spindle cells that exhibited positivity to CD34 simultaneously to BMP2;
      these results together coincided with a larger bone matrix deposited in all
      postsurgery periods analyzed. These results revealed that the WSAT may be an
      alternative to craniofacial bone reconstruction because the adipose tissue
      exhibited prominent immunoexpression of BMP2, which was coexpressed with stromal
      CD34+ cells, indicating the plasticity of CD34+ stem cells into osteoblasts, and
      in the adipocytes, facts that suggest bone tissue development through cellular
      transdifferentiation from adipocytes.

PMID- 22948635
TI  - Asymmetric class III malocclusion: association with cranial base deformation and
      occult torticollis.
AB  - The etiology of Angle class III malocclusion with facial asymmetry has not been
      fully elucidated. To investigate the etiology, patients with asymmetric
      prognathism (n = 30) from a single institution were assessed for previously
      undiagnosed torticollis and cranial base asymmetry. Presence of torticollis was
      determined by measuring restricted head movement when turning the head against a
      wall and cranial base tilt with upward gaze. Cranial base asymmetry was evaluated
      by preoperative three-dimensional computed tomography scans. Thirty-one percent
      of patients with prognathism presented with concurrent facial asymmetry. In
      patients with asymmetric prognathism, cranial base tilt was present on upward
      gaze in all patients; mean angle between head and wall was 31 degrees greater
      than that in control patients, and a 22% to 36% difference in the angle was
      present when comparing one side with the other. Based on these findings, all
      patients with asymmetric prognathism were found to be affected by torticollis. By
      computed tomography scan, 85% of these torticollis patients showed slight
      anteromedial displacement of the glenoid fossa ipsilateral to torticollis, and
      73% demonstrated temporal fossa shift of 4 mm or greater. The current study
      demonstrates a strong association between asymmetric class III malocclusion,
      torticollis, and cranial base asymmetry. We conclude that undiagnosed torticollis
      is a likely etiology for otherwise idiopathic cranial base asymmetry and that
      cranial base asymmetry in turn causes facial asymmetry and malocclusion. This
      study highlights the importance of evaluating cranial base asymmetry and
      torticollis in patients with class III malocclusion to allow for earlier
      treatment and improved outcomes.

PMID- 22948636
TI  - Clinical characteristics and treatment of blow-out fracture accompanied by
      canalicular laceration.
AB  - BACKGROUNDS: Blow-out fracture and canalicular laceration can occur
      simultaneously as a result of the same trauma. Despite its importance, little
      research has been conducted to identify clinical characteristics or surgical
      techniques for repair of a blow-out fracture accompanied by canalicular
      laceration. The aim of this study was to evaluate the clinical characteristics,
      the surgical approach, and the outcomes. METHODS: Thirty-four eyes of 34 patients
      who underwent simultaneous repair of canalicular laceration using silicone tube
      intubation and reconstruction of blow-out fracture were included. Medical records
      were retrospectively reviewed for patient demographics, nature of injury,
      affected canaliculus, location, and severity of blow-out fracture, associated
      facial bone fracture, ophthalmic diagnosis, length of follow-up period, and
      surgical outcome. RESULTS: Mean patient age was 40.0 years (range, 17-71 y). The
      mean follow-up was 7.3 months. Fist to the orbital area (10 patients, 29.4%) was
      the most common cause. There were 24 lower canalicular lacerations (70.6%), 6
      upper canalicular lacerations (17.6%), and 4 upper and lower canalicular
      lacerations (11.8%). Isolated medial wall fractures were most common (area A4:
      20/34, 58.8%). Fractures involving both the floor and medial wall and maxillo
      ethmoidal strut (areas A1, A2, A3, and A4) were the second most common (6/34,
      17.6%), and floor and medial wall with intact strut (areas A1, A2, and A4) were
      injured in 6 patients (17.6%). Pure inferior wall fractures were least frequent
      (areas A1 and A2: 2/34, 5.9%). The severity of the fracture was severe in most
      patients except for 1 linear fracture with tissue entrapment and 1 moderate
      medial wall fracture (32/34, 94.1%). There was lid laceration in 20 patients
      (58.8%). Nasal bone fracture (5/34, 14.7%) was the most common facial bone
      fracture. Tubes were removed at a mean of 3.3 months (range, 3-4 mo). In total,
      31 patients (91.2%) achieved complete success in canalicular laceration and blow
      out fracture repair. No significant complications were encountered. CONCLUSION:
      Fractures involving the medial wall with a lower canalicular laceration were the
      most common among concomitant blow-out fractures and canalicular lacerations. The
      severity of the fracture was most often classified as severe. Computed
      tomographic scan of the orbit and facial bones for identification of any
      additional injuries such as orbital wall and facial bone fractures should be
      performed in patients with canalicular laceration. To avoid disruption of the
      medial canthal area, repair of the canalicular laceration with silicone tube
      intubation was performed before reconstruction of the blow-out fracture through
      transconjunctival and transcaruncular approaches. Finally, the tube was fixed
      after blow-out fracture surgery, and these surgical orders yielded good surgical
      outcomes without complications.

PMID- 22948637
TI  - Surgical management of a congenital panda nevus with preexpanded triple forehead
      flaps and temporal island flap.
AB  - Congenital panda nevus or the divided nevus of the eyelids is a rare form of
      melanocytic nevus involving both upper and lower eyelids with the risk of future
      malignant transformation along with the patients' complaints about the cosmetic
      appearance. Delicate anatomic features of the eyelids and the limited skin
      redundancy of the periorbital region make the surgical removal and reconstruction
      difficult, even in mild cases with partial involvement of the eyelids. A case of
      congenital panda nevus involving upper and lower eyelids, the eyebrow, and part
      of the malar eminence and the nasal dorsum is presented. A multistaged surgical
      management of the lesion with staged excision and reconstruction with preexpanded
      forehead flaps, temporal island flap, and skin grafts is discussed.

PMID- 22948638
TI  - Intraoral approach for aesthetic restoration of posttraumatic zygomatic arch
      deformities.
AB  - Minimally invasive oral and maxillofacial surgery is now being developed for
      virtually all minor and major oral and maxillofacial surgeries, and developments
      are now focused on facial trauma surgery. This article assesses the feasibility
      of reducing isolated zygomatic arch fractures using the intraoral lateral
      coronoid approach. The procedure is cost-effective and timesaving, as it can be
      performed under local anesthesia in an emergency department or similar clinical
      setting and does not need postoperative hospitalization if no other comorbidities
      are present.

PMID- 22948639
TI  - Simultaneous Le Fort I, II, and III osteotomies for correction of midface
      deficiency in Apert disease.
AB  - Le Fort III osteotomy was usually applied to correct midface hypoplasia in Apert
      syndrome, and various surgical modifications have been developed in recent years.
      In this article, we reported the simultaneous Le Fort I, II, and III osteotomies
      for segmental advancement of midface deficiency involving nasal bones, zygoma,
      inferior orbital rims, and maxilla in an adult Chinese patient with Apert
      syndrome. To achieve the ideal advancement of different parts of midface
      simultaneously, we divided the midface into 4 segments, including nasal bone
      combined with upper portion of maxilla, lower portion of maxilla, and left and
      right zygoma, with simultaneous Le Fort I, Le Fort II, and Le Fort III
      osteotomies, and each segment was repositioned as required respectively to obtain
      ideal facial aesthetics and favorable occlusion. The long-term stability of bony
      segment advancements also was observed during 7-year follow-up. Compared with
      segmental distraction osteogenesis or multiple-stage surgery, which mainly
      applied to younger patients with more severe midface hypoplasia, this single
      stage strategy offered a reliable surgical alternative for treating adult patient
      with midface hypoplasia that should be corrected in different levels.

PMID- 22948640
TI  - New modification of cephalic resection of lateral crus in endonasal rhinoplasty.
AB  - A successful rhinoplasty mainly depends on maintaining adequate nasal tip
      projection and achieving the desired tip refinement. In endonasal rhinoplasty,
      the surgeon can modify the tip anatomy while still preserving the key structural
      support mechanisms. Herein, we describe a new modification of retrograde
      technique for the resection of the cephalic margin of the lateral crus in
      endonasal rhinoplasty in which a combined resection of the cephalic margin of the
      lateral crus and its underlying mucoperichondrium are performed.

PMID- 22948641
TI  - Management of distal posterior inferior cerebellar artery aneurysms.
AB  - BACKGROUND: Most of the posterior inferior cerebellar artery (PICA) aneurysms
      arise at the vertebral artery-PICA junction; distal PICA aneurysms are rare.
      Their clinical features and treatments are not fully understood. METHODS: This
      was a retrospective study. We reported 9 patients with the distal PICA aneurysms
      treated by surgical clipping or endovascular embolization in our neurosurgical
      center. RESULTS: All patients experienced sudden onset of headache with
      subarachnoid hemorrhage. The location of PICA aneurysms was at the anterior
      medullary (n = 4), tonsillomedullary (TM) (n = 1), and telovelotonsillar (n = 4).
      Surgical clipping was performed in 3 and endovascular coil in 6 patients. All the
      PICA aneurysms were occluded with parent artery preservation, and all of the
      patients achieved good recovery. CONCLUSIONS: Distal PICA aneurysm is
      exceptionally rare; it could be treated successfully with surgical clipping or
      endovascular treatments.

PMID- 22948642
TI  - Mandibular reconstruction after hemimandibulectomy.
AB  - Ameloblastoma is a benign tumor of the mandible, which is not commonly diagnosed
      in the early stages. The extensive mandible resection may be needed for
      treatment. In this report, we present 6-year follow-up results of a patient who
      had undergone hemimandibulectomy and mandible reconstruction with free
      vascularized fibular flap, costochondral rib graft to restoration of the
      temporomandibular joint, and iliac bone graft to enhance the vertical height of
      the mandible. The long-term results are very satisfactory.

PMID- 22948643
TI  - Modification in the technique of ear framework fabrication for congenital
      microtia.
AB  - BACKGROUND: Ear framework fabrication with autologous costal cartilage is
      considered to be one of the important factors for successful auricular
      reconstruction. Congenital microtia in adults has many particular physiological
      characteristics different from that in children. The authors report an effective
      ear framework-fabricating technique in congenital microtia in adults. Technical
      points regarding the reduction of the amount of costal cartilage harvested and
      the increase of the flexibility of the cartilage are discussed. METHODS: One
      hundred three adult patients diagnosed with unilateral congenital microtia were
      treated with skin expansion method for a 2-year period. The ear framework was
      fabricated using splicing method. The seventh costal cartilage was harvested from
      74 patients (with 35 lobular and 39 conchal types) for fabricating the ear
      framework. For the remaining 29 patients (with 19 lobular and 10 conchal types),
      both the seventh and eighth cartilages were harvested for fabrication. RESULT:
      Eighty-four patients (81.55%) were satisfied with the outcome of the
      reconstructed ear. Fourteen patients (13.60%) found the result acceptable,
      whereas 5 patients (4.85%) found the result unacceptable. Six patients (5.82%)
      showed different levels of absorption and cartilage deformation. Five patients
      (4.85%) were found to have the steel wire extruded. There were no postoperative
      complications related to chest wall deformity or that affected normal physical
      function. Ninety-three patients (90.29%) had good recovery of the chest wall. Ten
      patients (9.71%) had increased chest scar. CONCLUSIONS: Compared with traditional
      methods, the technique proposed is a simple approach that can effectively treat
      adult patients with congenital microtia. This kind of cartilage-harvesting and
      ear framework-fabricating technique is an appropriate management choice for
      congenital microtia in adults.

PMID- 22948644
TI  - Growing skull fractures after craniosynostosis repair:  risk factors and
      treatment algorithm.
AB  - Growing skull fractures (GSFs) are rare complications after severe head injuries
      in the early childhood and rarely occur after craniosynostosis repair. The aim of
      this study was to define an algorithm for sufficient treatment for GSF after
      craniofacial procedures. Literature research was performed to clarify risk
      factors for GSFs after cranial vault reshaping. Conclusions of the literature and
      experiences of the authors based on a case of GSF after craniofacial surgery were
      matched to establish guidelines for successful therapy.

PMID- 22948645
TI  - Microvascular decompression for hemifacial spasm.
AB  - OBJECTIVE: Although microvascular decompression (MVD) has been accepted as
      effective therapy for hemifacial spasm, failed surgery has been reported
      frequently. For a sophisticated neurosurgeon, an apparent offending artery is
      seldom missed. However, it is still an embarrassed situation when the
      neurovascular conflict site could not be approached. METHODS: Clinical data were
      collected from consecutive 211 MVDs in 2010. Intraoperative abnormal muscle
      response was recorded. Among them, the neurovascular conflict was not finally
      discovered in 3 patients, whom were then focused on. All patients were followed
      up for 6 to 15 months. RESULTS: In 17 of the 211 MVDs, the cerebellum was hard to
      be retracted because of adhesions. After careful dissection, a working space was
      finally created in the cerebellopontine angle. However, there still were 3 cases,
      whose neurovascular conflict site was unable to be discovered at last because of
      a branch of an artery embedded in the petrous bone and made the cerebellum
      unmovable. With navigation of real-time abnormal muscle response, the offending
      artery was moved away eventually even without exposing the conflict site.
      Postoperatively, all the patients were completely spasm-free immediately. No
      recurrence was noticed in the last follow-up period. CONCLUSIONS: The most
      important thing for a successful MVD operation is to remove the offending artery
      off the nerve. However, if the conflict site failed to be approached after
      endeavors, a successful MVD can still be achieved by relocating the offending
      artery with the guidance of real-time electromyography even without visualization
      of the confliction.

PMID- 22948646
TI  - Delayed sagittal sinus tear:  a complication of spring cranioplasty for sagittal
      craniosynostosis.
AB  - Spring cranioplasty is now a well-established surgical technique in the treatment
      of sagittal craniosynostosis. It is widely regarded as a less invasive modality
      compared with operations such as cranial vault remodeling. Indeed, very few
      complications have been described in the literature in association with spring
      cranioplasty. We present a case of delayed sagittal sinus tear with hemorrhage
      following spring cranioplasty in a 4-month-old patient with sagittal
      craniosynostosis. Likely causes of the injury are discussed highlighting sagittal
      sinus injury as a potential risk of spring cranioplasty.

PMID- 22948647
TI  - Correction of unilateral cleft lip nose deformity using nasal alar rim flap.
AB  - OBJECTIVE: The objective of this study was to show the use and effectiveness of
      nasal alar rim flap on the correction of unilateral cleft lip nasal deformity.
      METHODS: Thirty-one patients (age range, 10-29 years; mean, 15.1 years; 14 male
      and 17 female patients) with unilateral cleft lip underwent rhinoplasty surgery
      using alar rim flap. The excessive skin of nasal alar was marked, then a skin
      flap was raised. This flap can be transferred medially (type 1) or laterally
      (type 2) to narrow the nostril or to augment the nasal sill and, of course, to
      correct the alar web deformity. Preoperative and postoperative photographs were
      measured for photogrammetric analysis in 16 patients. RESULT: The alar rim flap
      used in patients with unilateral cleft lip made the nostrils more symmetrical.
      The nostril sill was augmented with flap type 1. The alar base width was narrowed
      with flap type 2 (P = 0.03). The alar web deformity was corrected. CONCLUSIONS:
      The alar rim flap could be an ideal treatment option for correction of alar web
      deformity in patients of unilateral cleft lip.

PMID- 22948648
TI  - Craniofacial principles in face transplantation.
AB  - BACKGROUND: Face transplantation allows the reconstruction of the previously
      nonreconstructible injury. Anthropometric landmarks are fixated to corresponding
      cephalometric landmarks to restore function and appearance, with emphasis on
      phonation, mastication, and functional upper airway. Currently, only a few face
      transplantations have been performed worldwide. A portion of these
      reconstructions involves combinations of hard and soft tissues of the midface.
      METHODS: Craniofacial and orthognathic considerations should be emphasized for
      functional effect in the planning and execution of face transplants that include
      both bone and soft tissue elements. These steps are taken to restore normal
      anatomy by fixating the midface into proper relationship with the skull base.
      Traditional orthognathic planning, using cephalometric parameters, often involves
      a line through sella and nasion as a reference for the skull base.
      Intraoperatively though, without a cephalograph, the sella-nasion plane is not
      accessible as a reference point. RESULTS: Postoperative analysis of our first
      face transplant recipient revealed that the Frankfort horizontal plane can
      alternatively serve as an accessible skull base reference point to guide the
      positioning of the midface. We have developed a technique to ensure fixation of
      the midface donor allograft in a proper functional relationship with the skull
      base, within 1 SD of Bolton normative data. CONCLUSIONS: "Reverse craniofacial
      planning" allows for precise fixation of the hard tissue components of the face
      transplant in relation to the skull base, as opposed to a "best fit" approach. We
      believe that this relationship results in the most anatomical restoration of
      occlusion, speech, and airway function.

PMID- 22948649
TI  - Preventive effect of dexmedetomidine in ischemia-reperfusion injury.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of dexmedetomidine
      on ischemia-reperfusion injury of epigastric island flaps of rats. METHODS:
      Eighty Wistar rats were divided into 4 groups. After the flap elevation, in group
      1, the flaps were sutured back without ischemic insult. Groups 2, 3, and 4 were
      exposed to ischemia for 12 hours. In groups 1 and 2, saline, in group 3, 10
      MUg/kg dexmedetomidine, and in group 4, 30 MUg/kg dexmedetomidine were
      administered i.p. 45 minutes before I/R periods. Each group was subdivided
      further into 2 equal groups (a and b). Tissue samples of groups 1a, 2a, 3a, and
      4a were obtained 12 hours after the reperfusion, and those of groups 1b, 2b, 3b,
      and 4b were obtained after 7 days. The necrotic areas were also calculated.
      Nitric oxide, malondialdehyde (MDA), and myeloperoxidase (MPO) activity were
      assessed in the tissue samples. RESULTS: Nitric oxide, MDA, and MPO activity
      levels in group 2a were significantly higher those in group 1a (P < 0.05). The
      levels in groups 3a and 4a were lower than those in group 2a (P < 0.05). Nitric
      oxide, MDA, and MPO activity levels were significantly higher in group 2b
      compared with group 1b (P < 0.05). The levels were lower in Groups 3b and 4b
      compared with group 2b (P < 0.05). Flap necrosis area was significantly lower in
      groups 3b and 4b than that in group 2b (P < 0.05). CONCLUSIONS: We conclude that
      administering dexmedetomidine before I/R periods can reduce ischemia-reperfusion
      injury of flaps, and it has a beneficial effect on flap survival.

PMID- 22948650
TI  - Ultrasonography in the evaluation of midpalatal suture in surgically assisted
      rapid maxillary expansion.
AB  - Surgically assisted rapid maxillary expansion (SARME), which combines
      orthodontics and surgery, is a well-established therapy for transverse maxillary
      hypoplasia in adults after sutural closure or completion of skeletal maturation.
      X-rays are usually the preferred monitoring technique for this treatment.
      Recently, ultrasound scanning has been used successfully in the follow-up of
      patients undergoing distraction osteogenesis. In this study, ultrasonography (US)
      was used in the evaluation of bone callus formation in the midpalatal suture in 3
      patients undergoing SARME. For each patient, US was performed immediately after
      active expansion, at 2 and 4 months of the expansion period, at the removal of
      the expander 6 months later, and at 2 months after expander removal. The results
      indicated that US might be a useful and accurate method to assess bone fill in
      the midpalatal suture in patients undergoing SARME. However, further studies are
      necessary to clarify the US scores in a larger patient group undergoing SARME.

PMID- 22948651
TI  - Involvement of the sphenosquamosal suture for unilateral coronal synostosis.
AB  - The etiology of the clinical entity commonly known as unilateral coronal
      synostosis is often described as the unilateral fusion of the coronal ring.
      However, recent theories have poorly explained the basis of the deformities
      associated with unilateral coronal synostosis. We retrospectively analyzed
      computed tomographic data sets from 18 patients who presented with unilateral
      coronal synostosis and arrived at our hospital between 1985 and 2010. Using three
      dimensional reconstructions of the computed tomographic images, analyses of the
      cranial base and measurements of each cranial bone were performed. As a result,
      the ipsilateral and contralateral basion-clinoid-pterion angles did not differ
      significantly (P = 0.49) and were almost identical in each case. However, the
      ipsilateral basion-partis-petrosae angle was wider than the corresponding
      contralateral angle (P < 0.001). In addition, the ipsilateral nasion-clinoid
      pterion angle and the sphenoid, zygomatic, and temporal bones on the ipsilateral
      side were significantly shorter than those on the contralateral side (P < 0.001).
      Based on a shortening ratio, the sphenoid bone was smaller (42.0% +/- 10.9%) than
      the temporal (68.9% +/- 7.58%) and zygomatic bones (71.1% +/- 8.38%). This
      difference was significant (P < 0.001). In conclusion, restricted growth
      potential of the central portion of the ipsilateral sphenoid bone was identified.
      We propose that the coronal ring, which includes the frontoparietal and
      frontosphenoidal sutures, and the sphenosquamosal suture are involved in
      unilateral coronal synostosis. Using our findings and the theory of Delashaw et
      al, the deformity observed in unilateral coronal synostosis can be explained more
      adequately and/or completely.

PMID- 22948652
TI  - Utility of the ultrasonic scalpel in mandibular distraction osteogenesis.
AB  - The purpose of this study was to describe our technique of bilateral mandibular
      distraction for micrognathia and to highlight the ultrasonic scalpel as an
      alternative to conventional saws in performing osteotomies for mandibular
      distraction osteogenesis. To do so, we retrospectively reviewed all patients who
      underwent mandibular distraction with an ultrasonic scalpel for tongue-based
      upper airway obstruction due to micrognathia between 2010 and 2011. Study outcome
      measures include operative blood loss, length of surgery, postoperative
      complications, and avoidance of a tracheostomy. Excel (Microsoft) was used to
      calculate averages, P values (2-tailed Student t test), and SDs for operative
      data, sleep studies, and cephalometric analysis. Nine patients--7 females and 2
      males--were distracted for a mean distance of 17 +/- 6 mm. Mean blood loss was 15
      +/- 7 mL, and the average length of surgery was 111 +/- 27 minutes. One patient
      returned to the operating room for debridement/washout of a wound infection, but
      distraction was continued without sequelae. There were no other postoperative
      complications. Resolution of airway obstruction was evidenced by clinical
      examination and avoidance of a tracheostomy in all cases. Based on these data, we
      feel that mandibular distraction with univector, internal distractors, and
      ultrasonic osteotomies at the mandibular angle is safe and efficacious at
      relieving tongue-based upper airway obstruction and avoiding a tracheostomy.

PMID- 22948653
TI  - Creating a neoconchal complex using the adjustable conchal sliding technique in
      prominent ear correction.
AB  - An oversized aural concha plays a significant role in prominent ear deformities
      and should be taken into consideration during preoperative examination. In the
      current study, we present a procedure known as the conchal sliding technique as
      an alternative to more disruptive methods. Twenty-four patients (9 females and 15
      males; 47 ears in total) underwent a conchal sliding procedure between 2006 and
      2010. During the surgery, a wide subperichondrial dissection is performed after a
      posterior elliptical incision. After the concha is exposed as a hemisphere, it is
      split along its long axis to reveal the medial and lateral cartilage segments.
      These segments are gently scrolled upon each other. Transposition of the lateral
      segment posteriorly to the medial segment replaces the whole ear toward the
      posterior direction. Three mattress sutures (4-0 polypropylene) reliably secure
      the repositioned and setback conchal bowl. If needed, an antihelix can be formed
      using neoconchal-scaphal mattress sutures. Median follow-up period was 24.3
      months (range, 6-48 mo). A unilateral hematoma developed in 1 patient and an
      anterior step deformity occurred in another. No recurrence, infection, necrosis
      of the skin, distortion of the auditory canal, or formation of keloid was
      observed in any of the patients. The median cephaloauricular angle was measured
      as 46 degrees before the surgery and 26 degrees after the surgery, whereas the
      distance between the helix and the mastoid was 23 mm before the surgery and 11 mm
      after the surgery. All the patients were satisfied with the results. This
      technique provides stable and natural results by creating a safe neoconchal
      complex. It may be a safe and reliable solution to an oversized aural concha,
      enabling natural-looking and positive cosmetic results.

PMID- 22948654
TI  - Asymmetric bilateral cleft lip:  classification and a surgical technique.
AB  - OBJECTIVE: The purpose of this study was to evaluate the symmetry in lip height
      after using our technique for bilateral cleft lip repair. A retrospective audit
      of 1 surgeon's outcome of 35 consecutively performed bilateral cleft lip repair
      with asymmetry between the right and left segments of the lip. Data were from the
      Outreach Surgical Center Program Lima Peru. METHODS: Since 2007, 158 patients
      with bilateral cleft lip were operated on using the Outreach Surgical Center
      Program Protocol. Of these patients, 35 (repaired using our technique) met the
      study criterion of having anthropometric measurements performed at least 1 year
      after surgery. Under general anesthesia, collection of lip height data (right and
      left sides) was performed immediately before the lip (before surgery) and palate
      (after surgery) surgery. Lip measurements were obtained using calipers. RESULTS:
      A 2-sample t-test with equal-variance analysis was performed to assess the
      statistical significance of differences between the right and left sides of the
      lip after surgery. This study found no statistically significant differences
      between the height of the right and left sides of the lip (P = 0.12) after lip
      repair using our technique. CONCLUSIONS: These findings suggest that this
      technique is a good alternative to repair asymmetric forms of bilateral cleft
      lip. The operative strategy for repair of an asymmetric bilateral cleft lip is
      determined by the degree of severity of the cleft.

PMID- 22948655
TI  - Transmaxillary osteogenic distraction with intraoral tooth-borne distractors.
AB  - Midfacial retrusion and class III malocclusion in maxillary hypoplasia are
      frequent sequelae in patients with cleft lip and palate. Similar deformities are
      seen in craniofacial dysostosis surgically treated in infancy. Recurrences after
      orthognathic surgery are unpredictable even using rigid fixations. Distraction
      osteogenesis, using Le Fort I osteotomies with external distractors, is
      uncomfortable for the patient, and internal distractors require a second
      procedure for removing the retractor. A new model of distraction osteogenesis is
      presented. Transmaxillary osteogenic distraction, using tooth-borne devices, is a
      simple method and allows ambulatory retraction of distractors. Osteogenesis
      between molars and premolars at the alveolar level is stable and allows
      orthodontic mobilization and dental implants. Anchorage in molars and maxillary
      tuberosities avoids velopharyngeal incompetence. Transmaxillary osteogenic
      distraction techniques are described, as well as results after 7 years of
      experience in 45 patients with maxillary hypoplasia. Results are satisfactory and
      stable, surgery is simple, and custom-made intraoral devices are easy to handle
      with minimal discomfort for the patients.

PMID- 22948656
TI  - Maxillomandibular tandem osteotomy with distraction osteogenesis for hemifacial
      microsomia.
AB  - Currently, simultaneous maxillomandibular distraction osteogenesis is a standard
      procedure for the correction of hemifacial microsomia. Many variations of the
      procedure have been reported. However, a common problem has been the extended
      duration of the procedure. In particular, the lengthy intermaxillary fixation
      period includes a prolonged distraction series that requires the restriction of
      oral food intake and creates significant stress for the patient, which has a
      profound effect on patient satisfaction. To avoid this stress, we have developed
      tandem osteotomy with distraction osteogenesis, termed the TODO procedure. The
      TODO procedure not only shortens the intermaxillary fixation period and the
      duration of therapy but also creates the ideal skeletal proportions, with
      horizontalization of the occlusal plane. The TODO procedure has the added benefit
      of producing a marked aesthetic improvement. The patient was extremely satisfied
      by the result and endured minimal stress.

PMID- 22948657
TI  - Anastomoses of the vestibular, cochlear, and facial nerves.
AB  - The internal auditory canal (IAC) is 10 to 17 mm in length, and the facial nerve
      and vestibulocochlear nerve, which consist of the cochlear nerve, the superior
      vestibular nerve, and the inferior vestibular nerve, run together in the IAC
      packaged in dura mater. Oort first described the vestibulocochlear anastomoses in
      1918, which is important for the understanding of the pathogenesis and
      pathophysiology of otologic disorders. The current study documents the existence
      of vestibulofacial and vestibulocochlear neural connections and topographical
      relationship of the nerves as part of a radiologic evaluation of 73 human
      temporal bones from brainstem to the lateral portion of IAC.

PMID- 22948658
TI  - Analysis of morbidity and mortality in surgical management of craniosynostosis.
AB  - Multidisciplinary care involving plastic surgery and neurosurgery is generally
      accepted as optimal to manage craniosynostosis to avoid complications and to
      identify patients at risk. We conducted a retrospective 30-year review of
      craniosynostosis surgery at a single major craniofacial institute to establish
      the rate and predictors of complications. Medical records of 796 consecutive
      patients who underwent primary surgery for craniosynostosis from 1981 to 2010 at
      our institute were analyzed for complications. Complications were defined as
      intraoperative and postoperative adverse events requiring changed management.
      Reoperation was defined as a repeat transcranial procedure. Multivariate logistic
      regression was used to identify predictors for complications or revision. Across
      the years, the procedures evolved from technically simple to complex, which
      increased complications but better outcomes. Complications occurred in 111
      patients (14%), and 33 (5.4%) needed major revision. Multivariate analysis
      identified multisuture and syndromic craniosynostosis, more recent surgeries,
      younger age (<9 months), spring-assisted cranioplasty, longer surgery, and
      greater transfusion as predictors of complications. Patients with syndromic and
      multisutural craniosynostosis and those operated on younger than 9 months had
      increased risk of major revision surgery for regression to phenotype. Our
      experience over 30 years indicates that pediatric transcranial craniosynostosis
      surgery can be safely carried out in our tertiary referral center. There were no
      deaths from primary surgery, and complication and reoperation rates mirror those
      of other published studies. Syndromic and complex craniosynostosis predicted both
      complications and need for major revision. Spring cranioplasty was associated
      with higher complications. Overall results support a recommended age for
      craniosynostosis surgery between 9 and 12 months.

PMID- 22948659
TI  - Pancreatic carcinoma cell lines reflect frequency and variability of cancer stem
      cell markers in clinical tissue.
AB  - BACKGROUND: Pancreatic cancer is one of the most deadly malignancies with
      insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are
      thought to be responsible for progression and therapy resistance. We investigated
      the potential of pancreatic cell lines for CSC research by analyzing to what
      extent they contain CSC populations and how representative these are compared to
      clinical tissue. METHODS: Six pancreatic cancer cell lines were analyzed by flow
      cytometry for CD326, CD133, CD44, CD24, CXCR4 and ABCG2. Subsequently, 70 primary
      pancreatic tissues were evaluated for CD326, CD133 and CD44 by
      immunohistochemistry. RESULTS: All the cell lines but one showed a stable
      expression pattern throughout biological replicates. Marker expression in
      clinical tissue of CD44 distinguished normal patients from pancreatic carcinoma
      patients with a sensitivity of 50% at 80% specificity and metastasized from
      nonmetastasized carcinomas with 69% sensitivity at 100% specificity. CONCLUSIONS:
      Our results indicate a link between elevated CD44 expression, malignancy and
      metastasis of pancreatic tissue. Furthermore, individual pancreatic cell lines
      show a substantial amount of cells with CSC properties which is comparable with
      interpatient variability detected in primary tissue. These pancreatic cancer cell
      lines could thus serve for urgently needed pharmacological CSC in vitro research.

PMID- 22948660
TI  - beta-Actin mRNA compartmentalization enhances focal adhesion stability and
      directs cell migration.
AB  - Directed cell motility is at the basis of biological phenomena such as
      development, wound healing, and metastasis. It has been shown that substrate
      attachments mediate motility by coupling the cell's cytoskeleton with force
      generation. However, it has been unclear how the persistence of cell
      directionality is facilitated. We show that mRNA localization plays an important
      role in this process, but the mechanism of action is still unknown. In this
      study, we show that the zipcode-binding protein 1 transports beta-actin mRNA to
      the focal adhesion compartment, where it dwells for minutes, suggesting a means
      for associating its localization with motility through the formation of stable
      connections between adhesions and newly synthesized actin filaments. In order to
      demonstrate this, we developed an approach for assessing the functional
      consequences of beta-actin mRNA and protein localization by tethering the mRNA to
      a specific location-in this case, the focal adhesion complex. This approach will
      have a significant impact on cell biology because it is now possible to forcibly
      direct any mRNA and its cognate protein to specific locations in the cell. This
      will reveal the importance of localized protein translation on various cellular
      processes.

PMID- 22948661
TI  - PTPN14 is required for the density-dependent control of YAP1.
AB  - Through an shRNA-mediated loss-of-function screen, we identified PTPN14 as a
      potential tumor suppressor. PTPN14 interacts with yes-associated protein 1
      (YAP1), a member of the hippo signaling pathway. We showed that PTPN14 promotes
      the nucleus-to-cytoplasm translocation of YAP1 during contact inhibition and thus
      inhibits YAP1 transactivation activity. Interestingly, PTPN14 protein stability
      was positively controlled by cell density. We identified the CRL2(LRR1) (cullin2
      RING ubiquitin ligase complex/leucine-rich repeat protein 1) complex as the E3
      ligase that targets PTPN14 for degradation at low cell density. Collectively,
      these data suggest that PTPN14 acts to suppress cell proliferation by promoting
      cell density-dependent cytoplasmic translocation of YAP1.

PMID- 22948662
TI  - CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in
      breast cancer cells.
AB  - Eukaryotic gene regulation implies that transcription factors gain access to
      genomic information via poorly understood processes involving activation and
      targeting of kinases, histone-modifying enzymes, and chromatin remodelers to
      chromatin. Here we report that progestin gene regulation in breast cancer cells
      requires a rapid and transient increase in poly-(ADP)-ribose (PAR), accompanied
      by a dramatic decrease of cellular NAD that could have broad implications in cell
      physiology. This rapid increase in nuclear PARylation is mediated by activation
      of PAR polymerase PARP-1 as a result of phosphorylation by cyclin-dependent
      kinase CDK2. Hormone-dependent phosphorylation of PARP-1 by CDK2, within the
      catalytic domain, enhances its enzymatic capabilities. Activated PARP-1
      contributes to the displacement of histone H1 and is essential for regulation of
      the majority of hormone-responsive genes and for the effect of progestins on cell
      cycle progression. Both global chromatin immunoprecipitation (ChIP) coupled with
      deep sequencing (ChIP-seq) and gene expression analysis show a strong overlap
      between PARP-1 and CDK2. Thus, progestin gene regulation involves a novel
      signaling pathway that connects CDK2-dependent activation of PARP-1 with histone
      H1 displacement. Given the multiplicity of PARP targets, this new pathway could
      be used for the pharmacological management of breast cancer.

PMID- 22948663
TI  - Spatially and genetically distinct control of seed germination by phytochromes A
      and B.
AB  - Phytochromes phyB and phyA mediate a remarkable developmental switch whereby,
      early upon seed imbibition, canopy light prevents phyB-dependent germination,
      whereas later on, it stimulates phyA-dependent germination. Using a seed coat
      bedding assay where the growth of dissected embryos is monitored under the
      influence of dissected endosperm, allowing combinatorial use of mutant embryos
      and endosperm, we show that canopy light specifically inactivates phyB activity
      in the endosperm to override phyA-dependent signaling in the embryo. This
      interference involves abscisic acid (ABA) release from the endosperm and distinct
      spatial activities of phytochrome signaling components. Under the canopy,
      endospermic ABA opposes phyA signaling through the transcription factor (TF)
      ABI5, which shares with the TF PIF1 several target genes that negatively regulate
      germination in the embryo. ABI5 enhances the expression of phytochrome signaling
      genes PIF1, SOMNUS, GAI, and RGA, but also of ABA and gibberellic acid (GA)
      metabolic genes. Over time, weaker ABA-dependent responses eventually enable phyA
      dependent germination, a distinct type of germination driven solely by embryonic
      growth.

PMID- 22948664
TI  - Inflammatory mass formation caused by gastric ectopic pancreas: report of a case.
AB  - Ectopic pancreas is a relatively rare condition that only occasionally causes the
      development of symptoms. This report presents a case of ectopic pancreas
      presenting as an inflammatory mass that formed in the gastric wall, which was
      successfully treated by surgical resection. A 32-year-old female was admitted due
      to a 3-year history of recurrent episodes of upper abdominal pain. Contrast
      enhanced computed tomography showed an irregularly enhanced mass of heterogeneous
      density in the gastric antrum. Gastroscopy revealed a submucosally elevated mass
      with a central umbilication in the gastric antrum. These studies indicated the
      presence of a 3-cm ectopic pancreas associated with inflammatory changes. The
      patient underwent laparoscopic local resection of the stomach. Microscopic
      examination of the lesion revealed heterogenic pancreatic tissue containing
      islets, dilated pancreatic ducts, and massive fibrosis in the gastric wall, with
      acinar atrophy and inflammatory cell infiltration. These findings indicated the
      formation of an inflammatory mass in the ectopic pancreas. 

PMID- 22948666
TI  - Innominate artery transection for patients with severe chest deformity: optimal
      indication and timing.
AB  - PURPOSE: The innominate artery sometimes compresses the trachea, leading to
      tracheomalacia and highly fatal tracheoinnominate fistula in patients with severe
      chest deformity. This study is focused on the indication of innominate artery
      transection for the definitive treatment of these complications. PATIENTS AND
      METHODS: We retrospectively analyzed the medical records of eight patients who
      underwent transection of innominate artery. RESULTS: All patients had developed
      severe chest deformity and their symptoms were life-threatening anoxic spell or
      endotracheal hemorrhage. Bronchoscopy showed tracheomalacia with or without
      pulsatile granulations on the anterior wall of the trachea underlying the
      innominate artery. In six cases who had previously undergone tracheostomy or
      laryngotracheal separation, the tracheal tube tip made granulations or
      tracheoinnominate fistulas. In addition to transection of innominate artery, the
      tracheoinnominate fistula was closed in two cases and the artery was transposed
      in one. All patients survived without neurologic complications and airway
      symptoms postoperatively. CONCLUSIONS: For patients with severe chest deformity,
      innominate artery transection is indicated when they have tracheal compression by
      the artery and need to be intubated through the compressed part of trachea to
      secure the airway. This would be the best timing to schedule the prophylactic
      operation.

PMID- 22948665
TI  - Thymus, thymoma and myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease. An autoantibody directed toward
      acetylcholine receptor (AChR) causes the destruction of the postsynaptic membrane
      and a reduction of the number of AChRs at neuromuscular junctions. A very
      puzzling, but interesting characteristic of myasthenia gravis is that many of the
      patients have an abnormality in their thymus. Many have a hyperplastic thymus
      with germinal centers, while others have a thymic tumor. How is the abnormality
      of the thymus related to myasthenia gravis? This review will summarize the
      existing evidence and try to find the missing link between the thymus and
      myasthenia gravis. The review will also comment on two distinct populations of
      myasthenia gravis patients without thymoma. The autoimmunity found in elderly
      patients is nonspecific and initiated via a different mechanism from the
      initiation of myasthenia gravis in younger patients.

PMID- 22948667
TI  - Can we predict the prognosis of resectable hepatoblastoma from serum alpha
      fetoprotein response during preoperative chemotherapy?
AB  - PURPOSE: The objective of this study was to clarify whether the alpha-fetoprotein
      (AFP) reduction rate during preoperative chemotherapy represents a prognostic
      factor for hepatoblastoma. METHOD: We divided 14 hepatoblastoma patients who
      underwent preoperative chemotherapy and curative resection into Group A (no
      recurrence; n = 10) and Group B (recurrence; n = 4). We then compared AFP levels
      before and after preoperative chemotherapy between groups. RESULT: Mean AFP level
      after completing the first cycle of chemotherapy was reduced to 7.28 % (range 1.2
      36.8 %) in Group A and 17.05 % (range 12.0-20.5 %) in Group B (p < 0.05). Mean
      AFP after total preoperative chemotherapy was reduced to 1.42 % (range 0.07-8.5
      %) in Group A and 7.55 % (range 3.4-12.4 %) in Group B (p < 0.02). Eight patients
      in whom AFP levels decreased >1 log after the first cycle of preoperative
      chemotherapy survived without recurrence. CONCLUSION: A large, early decrease in
      AFP level during preoperative chemotherapy may offer a strong indicator of
      survival. Patients in whom AFP levels do not decrease easily during preoperative
      chemotherapy may have increased risk of recurrence and should be followed very
      closely.

PMID- 22948669
TI  - Love and addiction: the devil is in the differences: a commentary on "the
      behavioral, anatomical and pharmacological parallels between social attachment,
      love and addiction".

PMID- 22948670
TI  - Site-specific and patterned growth of TiO2 nanotube arrays from e-beam evaporated
      thin titanium film on Si wafer.
AB  - Growth of TiO(2) nanotubes on thin Ti film deposited on Si wafers with site
      specific and patterned growth using a photolithography technique is demonstrated
      for the first time. Ti films were deposited via e-beam evaporation to a thickness
      of 350-1000 nm. The use of a fluorinated organic electrolyte at room temperature
      produced the growth of nanotubes with varying applied voltages of 10-60 V (DC)
      which remained stable after annealing at 500  degrees C. It was found that
      variation of the thickness of the deposited Ti film could be used to control the
      length of the nanotubes regardless of longer anodization time/voltage. Growth of
      the nanotubes on a SiO(2) barrier layer over a Si wafer, along with site-specific
      and patterned growth, enables potential application of TiO(2) nanotubes in
      NEMS/MEMS-type devices.

PMID- 22948668
TI  - Characterization of Highper, an ENU-induced mouse mutant with abnormal
      psychostimulant and stress responses.
AB  - RATIONALE: Chemical mutagenesis in the mouse is a forward genetics approach that
      introduces random mutations into the genome, thereby providing an opportunity to
      annotate gene function and characterize phenotypes that have not been previously
      linked to a given gene. OBJECTIVES: We report on the behavioral characterization
      of Highper, an N-ethyl-N-nitrosourea (ENU)-induced mutant mouse line. METHODS:
      Highper and B6 control mice were assessed for locomotor activity in the open
      field and home cage environments. Basal and acute restraint stress-induced
      corticosterone levels were measured. Mice were tested for locomotor response to
      cocaine (5, 20, 30, and 45 mg/kg), methylphenidate (30 mg/kg), and ethanol (0.75,
      1.25, and 1.75 g/kg). The rewarding and reinforcing effects of cocaine were
      assessed using conditioned place preference and self-administration paradigms.
      RESULTS: Highper mice are hyperactive during behavioral tests but show normal
      home cage locomotor behavior. Highper mice also exhibit a twofold increase in
      locomotor response to cocaine, methylphenidate, and ethanol and prolonged
      activation of the hypothalamic-pituitary-adrenal axis in response to acute
      stress. Highper mice are more sensitive to the rewarding and reinforcing effects
      of cocaine, although place preference in Highper mice appears to be significantly
      influenced by the environment in which the drug is administered. CONCLUSIONS:
      Altogether, our findings indicate that Highper mice may provide important
      insights into the genetic, molecular, and biological mechanisms underlying stress
      and the drug reward pathway.

PMID- 22948671
TI  - Content, placement, and acquisition of cancer education for Latino patient care:
      a qualitative study of medical and nursing students.
AB  - A focus group study was conducted with five medical and nursing education
      programs in Southeastern USA. Twenty-five third and fourth year students were
      queried about their experiences, beliefs, and attitudes regarding Latino patients
      and cancer care. A general inductive process using open coding and content
      comparison to identify emerging themes was used to analyze the qualitative data.
      Investigators used a process of constant comparison to identify emerging themes.
      Themes included: (1) importance of cultural specificity and relevance in cancer
      training, (2) timing and placement of cancer education in the curriculum,
      including classes and/or clinical rotations, (3) anatomical system specificity of
      cancer training-studying cancer in the context of a specific body system, and (4)
      the prevention-focused nature of cancer training. Results of the focus groups
      have been used to inform a web-based survey of medical and nursing students to
      identify gaps in cancer education specific to Latino populations.

PMID- 22948672
TI  - Robust suppression of HIV replication by intracellularly expressed reverse
      transcriptase aptamers is independent of ribozyme processing.
AB  - RNA aptamers that bind human immunodeficiency virus 1 (HIV-1) reverse
      transcriptase (RT) also inhibit viral replication, making them attractive as
      therapeutic candidates and potential tools for dissecting viral pathogenesis.
      However, it is not well understood how aptamer-expression context and cellular
      RNA pathways govern aptamer accumulation and net antiviral bioactivity. Using a
      previously-described expression cassette in which aptamers were flanked by two
      "minimal core" hammerhead ribozymes, we observed only weak suppression of
      pseudotyped HIV. To evaluate the importance of the minimal ribozymes, we replaced
      them with extended, tertiary-stabilized hammerhead ribozymes with enhanced self
      cleavage activity, in addition to noncleaving ribozymes with active site
      mutations. Both the active and inactive versions of the extended hammerhead
      ribozymes increased inhibition of pseudotyped virus, indicating that processing
      is not necessary for bioactivity. Clonal stable cell lines expressing aptamers
      from these modified constructs strongly suppressed infectious virus, and were
      more effective than minimal ribozymes at high viral multiplicity of infection
      (MOI). Tertiary stabilization greatly increased aptamer accumulation in viral and
      subcellular compartments, again regardless of self-cleavage capability. We
      therefore propose that the increased accumulation is responsible for increased
      suppression, that the bioactive form of the aptamer is one of the uncleaved or
      partially cleaved transcripts, and that tertiary stabilization increases
      transcript stability by reducing exonuclease degradation.

PMID- 22948673
TI  - A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer
      samples and inhibited growth of disseminated solid tumors in mice.
AB  - Targeting the tumor stroma in addition to the malignant cell compartment is of
      paramount importance to achieve complete tumor regression. In this work, we
      modified a previously designed tumor stroma-targeted conditionally replicative
      adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable
      to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed
      its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was
      able to replicate in fresh samples obtained from patients: (i) with primary human
      ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic
      disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 *
      10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude
      mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when
      the tumor contained a mix of malignant and SPARC-expressing stromal cells
      (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1
      was unable to replicate in normal human ovary samples while the wild-type virus
      can replicate. This study provides evidence on the lytic capacity of this CRAd
      and highlights the importance of targeting the stromal tissue in addition to the
      malignant cell compartment to achieve tumor regression.

PMID- 22948674
TI  - Different effect of Rho kinase inhibition on calcium signaling in rat isolated
      large and small arteries.
AB  - In addition to its role in the regulation of artery contraction, Rho kinase
      (ROCK) was reported to be involved in the cytosolic calcium response to
      vasoconstrictor agonists in rat aorta and superior mesenteric artery (SMA).
      However, it remains to be determined whether ROCK also contributes to calcium
      signaling in resistance arteries, which play a major role in blood pressure
      regulation. The investigation of the effect of ROCK inhibition on the calcium and
      contractile responses of rat resistance mesenteric artery (RMA), in comparison
      with aorta and SMA, indicated that the calcium response to noradrenaline was
      inhibited by the ROCK inhibitor Y-27632 in aorta and SMA but not in RMA. The
      effect of Y-27632 on the calcium signal was unaffected by cytochalasin-D. ROCK
      activation in noradrenaline-stimulated arteries was confirmed by the inhibition
      of myosin light chain phosphorylation by Y-27632. Moreover, noradrenaline-induced
      calcium signaling was similarly inhibited by nimodipine in aorta, SMA and RMA,
      but nimodipine sensitivity of the contraction increased from the aorta to the
      RMA, suggesting that the contraction was controlled by different sources of
      calcium. In pressurized RMA, Y-27632 and H-1152 depressed pressure-induced
      calcium responses and abolished myogenic contraction. These results stress the
      important differences in calcium signaling between conductance and resistance
      arteries.

PMID- 22948677
TI  - The cover. Machinery.

PMID- 22948680
TI  - Critics of US House proposal to ax AHRQ say idea is penny-wise and pound-foolish.

PMID- 22948681
TI  - European drug agency works to improve transparency, but skepticism remains.

PMID- 22948682
TI  - H3N2 flu virus infections increase during fair season.

PMID- 22948688
TI  - Glucose-insulin-potassium for suspected acute myocardial infarction.

PMID- 22948690
TI  - Depression treatment for patients with complex conditions.

PMID- 22948692
TI  - Prone vs supine positioning for breast cancer radiotherapy.

PMID- 22948694
TI  - The safety risks of innovation: the FDA's Expedited Drug Development Pathway.

PMID- 22948695
TI  - Clinical trial data as a public good.

PMID- 22948696
TI  - A piece of my mind. Worries.

PMID- 22948697
TI  - Aortic stiffness, blood pressure progression, and incident hypertension.
AB  - CONTEXT: Vascular stiffness increases with advancing age and is a major risk
      factor for age-related morbidity and mortality. Vascular stiffness and blood
      pressure pulsatility are related; however, temporal relationships between
      vascular stiffening and blood pressure elevation have not been fully delineated.
      OBJECTIVE: To examine temporal relationships among vascular stiffness, central
      hemodynamics, microvascular function, and blood pressure progression. DESIGN,
      SETTING, AND PARTICIPANTS: Longitudinal community-based cohort study conducted in
      Framingham, Massachusetts. The present investigation is based on the 2 latest
      examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 [last visit: January
      25, 2008]) of the Framingham Offspring study (recruited: 1971-1975). Temporal
      relationships among blood pressure and 3 measures of vascular stiffness and
      pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave
      velocity [CFPWV], forward wave amplitude [FWA], and augmentation index) were
      examined over a 7-year period in 1759 participants (mean [SD] age: 60 [9] years;
      974 women). MAIN OUTCOME MEASURES: The primary outcomes were blood pressure and
      incident hypertension during examination cycle 8. The secondary outcomes were
      CFPWV, FWA, and augmentation index during examination cycle 8. RESULTS: In a
      multivariable-adjusted regression model, higher FWA (beta, 1.3 [95% CI, 0.5-2.1]
      mm Hg per 1 SD; P = .002) and higher CFPWV (beta, 1.5 [95% CI, 0.5-2.6] mm Hg per
      1 SD; P = .006) during examination cycle 7 were jointly associated with systolic
      blood pressure during examination cycle 8. Similarly, in a model that included
      systolic and diastolic blood pressure and additional risk factors during
      examination cycle 7, higher FWA (odds ratio [OR], 1.6 [95% CI, 1.3-2.0] per 1 SD;
      P < .001), augmentation index (OR, 1.7 [95% CI, 1.4-2.0] per 1 SD; P < .001), and
      CFPWV (OR, 1.3 [95% CI, 1.0-1.6] per 1 SD; P = .04) were associated with incident
      hypertension during examination cycle 8 (338 cases [32%] in 1048 participants
      without hypertension during examination cycle 7). Conversely, blood pressure
      during examination cycle 7 was not associated with CFPWV during examination cycle
      8. Higher resting brachial artery flow (OR, 1.23 [95% CI, 1.04-1.46]) and lower
      flow-mediated dilation (OR, 0.80 [95% CI, 0.67-0.96]) during examination cycle 7
      were associated with incident hypertension (in models that included blood
      pressure and tonometry measures collected during examination cycle 7).
      CONCLUSION: In this cohort, higher aortic stiffness, FWA, and augmentation index
      were associated with higher risk of incident hypertension; however, initial blood
      pressure was not independently associated with risk of progressive aortic
      stiffening.

PMID- 22948698
TI  - Association of clopidogrel treatment with risk of mortality and cardiovascular
      events following myocardial infarction in patients with and without diabetes.
AB  - CONTEXT: Pharmacodynamic studies have shown that persistently high platelet
      reactivity is common in patients with diabetes in spite of clopidogrel treatment.
      Clinical trials have not convincingly demonstrated that clopidogrel benefits
      patients with diabetes as much patients without diabetes. OBJECTIVES: To estimate
      the clinical effectiveness associated with clopidogrel treatment after myocardial
      infarction (MI) in patients with diabetes. DESIGN, SETTING, AND PATIENTS: By
      individual-level linkage of the Danish nationwide administrative registries
      between 2002-2009, patients who were hospitalized with incident MI and who had
      survived and not undergone coronary artery bypass surgery 30 days after discharge
      were followed up for as long as 1 year (maximally until December 31, 2009).
      Adjusted for age, sex, comorbidity, calendar year, concomitant pharmacotherapy,
      and invasive interventions, hazard ratios that were associated with clopidogrel
      in patients with and without diabetes were analyzed by Cox proportional-hazard
      models and propensity score-matched models. MAIN OUTCOME MEASURES: All-cause
      mortality, cardiovascular mortality, and a composite end point of recurrent MI
      and all-cause mortality. RESULTS: Of the 58,851 patients included in the study,
      7247 (12%) had diabetes and 35,380 (60%) received clopidogrel. In total, 1790
      patients (25%) with diabetes and 7931 patients (15%) without diabetes met the
      composite end point. Of these, 1225 (17%) with and 5377 (10%) without diabetes
      died. In total, 978 patients (80%) with and 4100 patients (76%) without diabetes
      died of events of cardiovascular origin. For patients with diabetes who were
      treated with clopidogrel, the unadjusted mortality rates (events/100 person
      years) were 13.4 (95% CI, 12.8-14.0) vs 29.3 (95% CI, 28.3-30.4) for those not
      treated. For patients without diabetes who were treated with clopidogrel, the
      unadjusted mortality rates were 6.4 (95% CI, 6.3-6.6) vs 21.3 (95% CI, 21.0-21.7)
      for those not treated. However, among patients with diabetes vs those without
      diabetes, clopidogrel was associated with less effectiveness for all-cause
      mortality (HR, 0.89 [95% CI, 0.79-1.00] vs 0.75 [95% CI, 0.70-0.80]; P for
      interaction, .001) and for cardiovascular mortality (HR, 0.93 [95% CI, 0.81-1.06]
      vs 0.77 [95% CI, 0.72-0.83]; P for interaction, .01) but not for the composite
      end point (HR, 1.00 [95% CI, 0.91-1.10] vs 0.91 [95% CI, 0.87-0.96]; P for
      interaction, .08). Propensity score-matched models gave similar results.
      CONCLUSION: Among patients with diabetes compared with patients without diabetes,
      the use of conventional clopidogrel treatment after MI was associated with lower
      reduction in the risk of all-cause death and cardiovascular death.

PMID- 22948699
TI  - Prevalence and prognosis of unrecognized myocardial infarction determined by
      cardiac magnetic resonance in older adults.
AB  - CONTEXT: Unrecognized myocardial infarction (MI) is prognostically important.
      Electrocardiography (ECG) has limited sensitivity for detecting unrecognized MI
      (UMI). OBJECTIVE: Determine prevalence and mortality risk for UMI detected by
      cardiac magnetic resonance (CMR) imaging or ECG among older individuals. DESIGN,
      SETTING, AND PARTICIPANTS: ICELAND MI is a cohort substudy of the Age,
      Gene/Environment Susceptibility-Reykjavik Study (enrollment January 2004-January
      2007) using ECG or CMR to detect UMI. From a community-dwelling cohort of older
      individuals in Iceland, data for 936 participants aged 67 to 93 years were
      analyzed, including 670 who were randomly selected and 266 with diabetes. MAIN
      OUTCOME MEASURES: Prevalence and mortality of MI through September 1, 2011.
      Results reported with 95% confidence limits and net reclassification improvement
      (NRI). RESULTS: Of 936 participants, 91 had recognized MI (RMI) (9.7%; 95% CI, 8%
      to 12%), and 157 had UMI detected by CMR (17%; 95% CI, 14% to 19%), which was
      more prevalent than the 46 UMI detected by ECG (5%; 95% CI, 4% to 6%; P < .001).
      Participants with diabetes (n = 337) had more UMI detected by CMR than by ECG (n
      = 72; 21%; 95% CI, 17% to 26%, vs n = 15; 4%; 95% CI, 2% to 7%; P < .001).
      Unrecognized MI by CMR was associated with atherosclerosis risk factors, coronary
      calcium, coronary revascularization, and peripheral vascular disease. Over a
      median of 6.4 years, 30 of 91 participants (33%; 95% CI, 23% to 43%) with RMI
      died, and 44 of 157 participants (28%; 95% CI, 21% to 35%) with UMI died, both
      higher rates than the 119 of 688 participants (17%; 95% CI, 15% to 20%) with no
      MI who died. Unrecognized MI by CMR improved risk stratification for mortality
      over RMI (NRI, 0.34; 95% CI, 0.16 to 0.53). Adjusting for age, sex, diabetes, and
      RMI, UMI by CMR remained associated with mortality (hazard ratio [HR], 1.45; 95%
      CI, 1.02 to 2.06, absolute risk increase [ARI], 8%) and significantly improved
      risk stratification for mortality (NRI, 0.16; 95% CI, 0.01 to 0.31), but UMI by
      ECG did not (HR, 0.88; 95% CI, 0.45 to 1.73; ARI, -2%; NRI, -0.05; 95% CI, -0.17
      to 0.05). Compared with those with RMI, participants with UMI by CMR used cardiac
      medications such as statins less often (36%; 95% CI, 28% to 43%, or 56/157, vs
      73%; 95% CI, 63% to 82%, or 66/91; P < .001). CONCLUSIONS: In a community-based
      cohort of older individuals, the prevalence of UMI by CMR was higher than the
      prevalence of RMI and was associated with increased mortality risk. In contrast,
      UMI by ECG prevalence was lower than that of RMI and was not associated with
      increased mortality risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01322568.

PMID- 22948700
TI  - Risk of malignancies in patients with rheumatoid arthritis treated with biologic
      therapy: a meta-analysis.
AB  - CONTEXT: Concerns exist regarding the potential development of malignancies in
      patients with rheumatoid arthritis (RA) who are receiving biologic response
      modifiers (BRMs). OBJECTIVE: To assess the risk of malignancy in patients with RA
      enrolled in randomized controlled trials (RCTs) of BRMs. DATA SOURCES: Electronic
      databases, conference proceedings, and websites of regulatory agencies were
      searched for RCTs evaluating abatacept, adalimumab, anakinra, certolizumab,
      etanercept, golimumab, infliximab, rituximab, and tocilizumab in RA from
      inception through July 9, 2012. STUDY SELECTION: Independent selection of studies
      included RCTs that compared the safety of any BRMs used in RA patients with
      placebo and/or any traditional disease-modifying antirheumatic drugs with a
      minimum of 24 weeks of follow-up. DATA EXTRACTION: Independent reviewers selected
      studies and extracted data on quality and outcomes. Pooled estimates and 95%
      confidence intervals were calculated for each BRM. RESULTS: Sixty-three RCTs with
      29,423 patients were analyzed. No statistically significant increased risk of
      developing malignancy was observed. Of the 29,423 patients, 211 developed a
      malignancy during the trial (118 solid tumors, 48 skin cancers, 14 lymphomas, 5
      hematologic nonlymphomas, and 26 not specified). The incidence rate for any
      malignancy during the first year of therapy was very low in the BRM plus
      methotrexate group (0.77%; 95% CI, 0.65%-0.92%), the BRM monotherapy group
      (0.64%; 95% CI, 0.42%-0.95%), and the controls (0.66%; 95% CI, 0.52%-0.84%).
      Anakinra plus methotrexate showed lower odds compared with methotrexate alone
      (Peto odds ratio, 0.11; 95% CI, 0.03-0.45). No statistically significant risk was
      observed for specific cancer sites, although the Peto odds ratio for lymphoma was
      2.1 (95% CI, 0.55-8.4) in patients receiving tumor necrosis factor inhibitors
      compared with controls. CONCLUSION: The use of BRMs among patients with RA
      included in RCTs of at least 6 months' duration was not significantly associated
      with an increased risk of malignancy compared with other disease-modifying
      antirheumatic drugs or with placebo.

PMID- 22948702
TI  - Atherogenic vascular stiffness and hypertension: cause or effect?

PMID- 22948701
TI  - Older adults with severe, treatment-resistant depression.
AB  - Depression is a common, disabling, and costly condition encountered in older
      patients. Effective strategies for detection and treatment of late-life
      depression are summarized based on a case of a 69-year-old woman who struggled
      with prolonged depression. Clinicians should screen older patients for depression
      using a standard rating scale, initiate treatment such as antidepressant
      medications or evidence-based psychotherapy, and monitor depression symptoms.
      Patients who are not improving should be considered for psychiatric consultation
      and treatment changes including electroconvulsive therapy. Several changes in
      treatment approaches are usually needed before patients achieve complete
      remission. Maintenance treatment and relapse-prevention planning (summarization
      of early warning signs for depression, maintenance treatments such as
      medications, and other strategies to reduce the risk of relapse [eg, regular
      physical activity or pleasant activities]) can reduce the risk of relapse.
      Collaborative programs, in which primary care clinicians work closely with mental
      health specialists following a measurement-based treatment-to-target approach,
      are significantly more effective than typical primary care treatment.

PMID- 22948703
TI  - Antiplatelet therapy following myocardial infarction in patients with diabetes.

PMID- 22948707
TI  - JAMA patient page. Antibiotics to prevent infective endocarditis.

PMID- 22948708
TI  - Measuring enactment of innovations and the factors that affect implementation and
      sustainability: moving toward common language and shared conceptual
      understanding.
AB  - This article describes research that focuses on the concern that researchers are
      unable to fully realize the potential value of their collective efforts because
      they do not have shared conceptual or operational tools for communicating
      assumptions, ideas, research strategies, or findings with others outside, or even
      within their disciplines. This research, through the lens of measuring
      implementation of educational programs, has taken steps toward bringing
      researchers' varied pictures of understanding into a coherent landscape. This
      article describes a conceptual framework for describing aspects of
      implementation, a conceptual framework for describing the factors that affect
      implementation, and tools for measuring each. It describes the challenges
      addressed in the development of these approaches, and the application of these
      approaches to current studies in education and other fields in the social
      sciences. In doing so, it demonstrates that meaningful communication between
      researchers and accumulation of knowledge across fields is possible, and
      necessary.

PMID- 22948709
TI  - Adenosine transport blockade restores attenuated cardioprotective effects of
      adenosine preconditioning in the isolated diabetic rat heart: potential crosstalk
      with opioid receptors.
AB  - Considering the reduced ability of cardiac fibroblasts to release adenosine and
      increased ability of interstitial adenosine uptake during diabetes mellitus, the
      present study investigated the effect of adenosine preconditioning and the
      existence of cross-talk with opioid receptor activation in the diabetic rat heart
      subjected to ischemia-reperfusion (I/R). Langendorff-perfused normal and
      streptozotocin (65 mg/kg, i.p., once)-administered diabetic (after 8-weeks) rat
      hearts were subjected to 30-min global ischemia and 120-min reperfusion.
      Myocardial infarct size using triphenyltetrazolium chloride staining, markers of
      cardiac injury such as lactate dehydrogenase (LDH) and creatine kinase (CK-MB)
      release, coronary flow rate (CFR) and myocardial oxidative stress were assessed.
      The diabetic rat heart showed high degree of I/R injury with increased LDH and CK
      MB release, high oxidative stress and reduced CFR as compared to the normal rat
      heart. The adenosine preconditioning (10 MUM) afforded cardioprotection against
      I/R injury in the normal rat heart that was prevented by naloxone (100 MUM) pre
      treatment. Conversely, adenosine preconditioning-induced cardioprotection was
      abolished in the diabetic rat heart. However, co-administration of dipyridamole
      (100 MUM), adenosine reuptake inhibitor, markedly restored the cardioprotective
      effect of adenosine preconditioning in the diabetic rat heart, and this effect
      was also abolished by naloxone pre-treatment. The reduced myocardial availability
      of extracellular adenosine might explain the inability of adenosine
      preconditioning to protect the diabetic myocardium. The pharmacological elevation
      of extracellular adenosine restores adenosine preconditioning-mediated
      cardioprotection in the diabetic myocardium by possibly involving opioid receptor
      activation.

PMID- 22948710
TI  - The dual-targeted HER1/HER2 tyrosine kinase inhibitor lapatinib strongly
      potentiates the cardiac myocyte-damaging effects of doxorubicin.
AB  - The anticancer drug lapatinib (Tykerb) is a dual tyrosine kinase inhibitor
      targeting the HER2 (ERBB2) and EGFR (ERBB1, HER1) pathways that have been shown
      in clinical trials to display some cardiotoxicity. Because trastuzumab also
      targets HER2 receptors, the lapatinib/doxorubicin combination provides a good
      model to probe the mechanism of the increased cardiotoxicity caused by the
      concurrent use of trastuzumab and doxorubicin. Using a neonatal rat cardiac
      myocyte model, we have investigated the ability of lapatinib alone and in
      combination with doxorubicin to damage myocytes. Lapatinib treatment alone only
      slightly induced myocyte damage. However, doxorubicin-induced myocyte damage was
      greatly potentiated by the addition of nanomolar lapatinib concentrations.
      Lapatinib alone treatment decreased phosphorylated ERK (MAPK), which may have, in
      part, contributed to the increased myocyte damage. As measured by flow cytometry,
      lapatinib-treated myocytes displayed an increased accumulation of doxorubicin. As
      lapatinib is a strong inhibitor of several ATP-dependent ABC-type efflux
      transporters, this likely occurred because lapatinib blocked doxorubicin efflux,
      thereby increasing intracellular doxorubicin concentrations and, thus, increasing
      myocyte damage. These results suggest that the clinical use of concurrent
      doxorubicin and lapatinib should be approached with care due to the possibility
      of lapatinib increasing doxorubicin cardiotoxicity.

PMID- 22948711
TI  - Nanoscale engineering of radiation tolerant silicon carbide.
AB  - Radiation tolerance is determined by how effectively the microstructure can
      remove point defects produced by irradiation. Engineered nanocrystalline SiC with
      a high-density of stacking faults (SFs) has significantly enhanced recombination
      of interstitials and vacancies, leading to self-healing of irradiation-induced
      defects. While single crystal SiC readily undergoes an irradiation-induced
      crystalline to amorphous transformation at room temperature, the nano-engineered
      SiC with a high-density of SFs exhibits more than an order of magnitude increase
      in radiation resistance. Molecular dynamics simulations of collision cascades
      show that the nano-layered SFs lead to enhanced mobility of interstitial Si
      atoms. The remarkable radiation resistance in the nano-engineered SiC is
      attributed to the high-density of SFs within nano-sized grain structures that
      significantly enhance point defect annihilation.

PMID- 22948712
TI  - Fine tuning of plasmonic properties of monolayers of weakly interacting silver
      nanocubes on thin silicon films.
AB  - Plasmonic properties, such as refractive index sensitivity (RIS), surface
      enhancement of the Raman signal (SERS), fluorescence quenching, and
      photocatalytic activity, of monolayers of weakly interacting monodisperse silver
      nanocubes were qualitatively modified in a very well controlled manner by
      supporting them on thin silicon films with varying thickness. Such fine
      tunability is made possible by the strong dependence of the nanocube dipolar (D)
      and quadrupolar (Q) plasmon mode hybridization on the refractive index of the
      supporting substrate. By increasing the Si film thickness from zero to ~25 nm we
      were able to "shift" the D resonance mode by up to 200 nm for ~80 nm cubes
      without significantly affecting the Q mode. The silicon supported nanocubes
      showed a significant improvement in RIS via the Q mode with a figure of merit
      greater than 6.5 and about an order of magnitude enhancement of the SERS signal
      due to the stronger electric field created by the D mode. Such substrates also
      showed a ~10 times decrease in rhodamine 6G fluorescence as well as the rates of
      amorphous carbon formation. The study proposes a new way to design and engineer
      plasmonic nanostructures.

PMID- 22948713
TI  - Bone-bonding properties of Ti metal subjected to acid and heat treatments.
AB  - The effects of surface treatment on the bone-bonding properties of Ti metal were
      examined by both mechanical detaching test and histological observation after
      implantation into rabbit tibiae for various periods ranging from 4 to 26 weeks.
      The bone-bonding ability of Ti metal, which is extremely low as it is abraded,
      was hardly increased by simple heat treatment at 600  degrees C or treatment with
      H(2)SO(4)/HCl mixed acid alone, but was markedly increased by the heat treatment
      after the acid treatment. Even Ti metal that had been previously subjected to
      NaOH treatment showed considerably high bone-bonding ability after acid and heat
      treatments. Such high bonding abilities were attributed to their high apatite
      forming ability in the body environment. Their high apatite-forming abilities
      were attributed to a high positive surface charge, and not to the type of
      crystalline phase or specific roughness of their surfaces. The present study has
      demonstrated that acid and subsequent heat treatments are effective for
      conferring stable fixation properties on Ti metal implants.

PMID- 22948714
TI  - Platypnea-orthodeoxia syndrome in review: defining a new disease?.
AB  - Platypnea-orthodeoxia syndrome is an intriguing condition that comprehends
      multiple pathologic phenomena. It requires a high clinical suspicion and is
      probably underdiagnosed. Its identification has therapeutic implications and can
      have a huge impact on the patient's everyday life. We made a review of the
      literature and analyzed 188 cases described thus far, trying to identify the
      underlying mechanisms and risk factors. We propose that a separate entity is
      created within the spectrum of platypnea-orthodeoxia syndrome that is responsible
      for the majority of cases, namely platypnea-orthodeoxia disease, which would be
      defined as the existence of an interatrial communication, with a right-to-left
      shunt, normal pressure in the right atrium and, of course, platypnea and
      orthodeoxia. Most patients with this disease were submitted to percutaneous
      closure of the patent foramen ovale or atrial septal defect, with favorable
      results, making it the first-line therapeutic approach nowadays.

PMID- 22948715
TI  - Acquired agminated melanocytic naevi: report of two cases and review of the
      literature.

PMID- 22948716
TI  - Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to
      centromere-associated protein E inhibition.
AB  - Inhibition of centromere-associated protein-E (CENP-E) has demonstrated
      preclinical anti-tumor activity in a number of tumor types including
      neuroblastoma. A potent small molecule inhibitor of the kinesin motor activity of
      CENP-E has recently been developed (GSK923295). To identify an effective drug
      combination strategy for GSK923295 in neuroblastoma, we performed a screen of
      siRNAs targeting a prioritized set of genes that function in therapeutically
      tractable signaling pathways. We found that siRNAs targeted to extracellular
      signal-related kinase 1 (ERK1) significantly sensitized neuroblastoma cells to
      GSK923295-induced growth inhibition (p = 0.01). Inhibition of ERK1 activity using
      pharmacologic inhibitors of mitogen-activated ERK kinase (MEK1/2) showed
      significant synergistic growth inhibitory activity when combined with GSK923295
      in neuroblastoma, lung, pancreatic and colon carcinoma cell lines. Synergistic
      growth inhibitory activity of combined MEK/ERK and CENP-E inhibition was a result
      of increased mitotic arrest and apoptosis. There was a significant correlation
      between ERK1/2 phosphorylation status in neuroblastoma cell lines and GSK923295
      growth inhibitory activity (r = 0.823, p = 0.0006). Consistent with this result
      we found that lung cancer cell lines harboring RAS mutations, which leads to
      oncogenic activation of MEK/ERK signaling, were significantly more resistant than
      cell lines with wild-type RAS to GSK923295-induced growth inhibition (p = 0.047).
      Here we have identified (MEK/ERK) activity as a potential biomarker of relative
      GSK923295 sensitivity and have shown the synergistic effect of combinatorial
      MEK/ERK pathway and CENP-E inhibition across different cancer cell types
      including neuroblastoma.

PMID- 22948717
TI  - Yes is a central mediator of cell growth in malignant mesothelioma cells.
AB  - The constitutive activation of the Src family kinases (SFKs) has been established
      as a poor prognostic factor in malignant mesothelioma (MM), however, the family
      member(s) which contribute to the malignancy have not been defined. This study
      aimed to identify the SFK member(s) contributing to cell growth using RNA
      interference in various MM cell lines. Silencing of Yes but not of c-Src or Fyn
      in MM cells leads to cell growth suppression. This suppressive effect caused by
      Yes silencing mainly depends on G1 cell cycle arrest and partly the induction of
      apoptosis. Also, the knockout of Yes induces the inactivation of beta-catenin
      signaling and subsequently decreases the levels of cyclin D necessary for G1-S
      transition in the cell cycle. In addition, Yes knockout has less effect on cell
      growth suppression in beta-catenin-deficient H28 MM cells compared to other MM
      cells which express the catenin. Overall, we conclude that Yes is a central
      mediator for MM cell growth that is not shared with other SFKs such as c-Src.

PMID- 22948719
TI  - Diversity and plasticity of sex determination and differentiation in fishes.
AB  - Among vertebrates, fishes show an exceptional range of reproductive strategies
      regarding the expression of their sexuality. Fish sexualities were categorized
      into gonochorism, synchronous/sequential hermaphrodite, or unisexual
      reproduction. In gonochoristic fishes, sex is determined genetically or by
      environmental factors. After sex determination, the gonads are differentiated
      into ovary or testis, with the sex remaining fixed for the entire life cycle. In
      contrast, some sequential hermaphrodite fishes can change their sex from male to
      female (protandrous), female to male (protogynous), or serially (bi-directional
      sex change) in their life cycle. In many cases, sex change is cued by social
      factors such as the disappearance of a male or female from a group. This unique
      diversity in fishes provides an ideal animal model to investigate sex
      determination and differentiation in vertebrates. This review first discusses
      genetic-orientated sex determination mechanisms. Then, we address the gonadal sex
      differentiation process in a gonochoristic fish, using an example of the Nile
      tilapia. Finally, we discuss various types of sex change that occur in
      hermaphrodite fishes.

PMID- 22948718
TI  - Soluble epoxide hydrolase inhibition exhibits antihypertensive actions
      independently of nitric oxide in mice with renovascular hypertension.
AB  - OBJECTIVE: The present study was performed to examine whether the blood pressure
      (BP)-lowering effects of soluble epoxide hydrolase (sEH) inhibition in two
      kidney, one-clip (2K1C) Goldblatt hypertension are nitric oxide (NO) dependent.
      METHODS: Mice lacking the endothelial NO synthase (eNOS) gene (eNOS-/-) and their
      wild-type controls (eNOS+/+) underwent clipping of one renal artery. BP was
      monitored by radiotelemetry and the treatment with the sEH inhibitor cis-4-[4-(3
      adamantan-1-yl-ureido)cyclohex-yloxy]-benzoic acid (c-AUCB) was initiated on day
      25 after clipping and lasted for 14 days. Renal concentrations of
      epoxyeicosatrienoic acids (EETs) and their inactive metabolite
      dihydroxyeicosatrienoic acids (DHETs) were measured in the nonclipped kidney.
      Renal NO synthase (NOS) activity was determined by measuring the rate of
      formation of L-[(14)C]citruline from L-[(14)C]arginine. RESULTS: Treatment with
      the sEH inhibitor elicited similar BP decreases that were associated with
      increases in daily sodium excretion in 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice.
      In addition, treatment with the sEH inhibitor increased the ratio of EETs/DHETs
      in the nonclipped kidney of 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice. Treatment
      with the sEH inhibitor did not alter renal NOS activity in any of the
      experimental groups. CONCLUSIONS: Collectively, our present data suggest that the
      BP-lowering effects of chronic sEH inhibition in 2K1C mice are mainly associated
      with normalization of the reduced availability of biologically active EETs in the
      nonclipped kidney and their direct natriuretic actions.

PMID- 22948720
TI  - Evaluation of automated image registration algorithm for image-guided
      radiotherapy (IGRT).
AB  - The performance of an image registration (IR) software was evaluated for
      automatically detecting known errors simulated through the movement of ExactCouch
      using an onboard imager. Twenty-seven set-up errors (11 translations, 10
      rotations, 6 translation and rotation) were simulated by introducing offset up to
      +/- 15 mm in three principal axes and 0 degrees  to +/- 1 degrees  in yaw. For
      every simulated error, orthogonal kV radiograph and cone beam CT were acquired in
      half-fan (CBCT_HF) and full-fan (CBCT_FF) mode. The orthogonal radiographs and
      CBCTs were automatically co-registered to reference digitally reconstructed
      radiographs (DRRs) and planning CT using 2D-2D and 3D-3D matching software based
      on mutual information transformation. A total of 79 image sets (ten pairs of kV X
      rays and 69 session of CBCT) were analyzed to determine the (a) reproducibility
      of IR outcome and (b) residual error, defined as the deviation between the known
      and IR software detected displacement in translation and rotation. The
      reproducibility of automatic IR of planning CT and repeat CBCTs taken with and
      without kilovoltage detector and kilovoltage X-ray source arm movement was
      excellent with mean SD of 0.1 mm in the translation and 0.0 degrees  in rotation.
      The average residual errors in translation and rotation were within +/- 0.5 mm
      and +/- 0.2 degrees , +/- 0.9 mm and +/- 0.3 degrees , and +/- 0.4 mm and +/- 0.2
      degrees  for setup simulated only in translation, rotation, and both translation
      and rotation. The mean (SD) 3D vector was largest when only translational error
      was simulated and was 1.7 (1.1) mm for 2D-2D match of reference DRR with
      radiograph, 1.4 (0.6) and 1.3 (0.5) mm for 3D-3D match of reference CT and CBCT
      with full fan and half fan, respectively. In conclusion, the image-guided
      radiation therapy (IGRT) system is accurate within 1.8 mm and 0.4 degrees  and
      reproducible under control condition. Inherent error from any IGRT process should
      be taken into account while setting clinical IGRT protocol.

PMID- 22948721
TI  - Impact of the specific mutation in KRAS codon 12 mutated tumors on treatment
      efficacy in patients with metastatic colorectal cancer receiving cetuximab-based
      first-line therapy: a pooled analysis of three trials.
AB  - PURPOSE: This study investigated the impact of specific mutations in codon 12 of
      the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic
      colorectal cancer (mCRC). PATIENTS: Overall, 119 patients bearing a KRAS mutation
      in codon 12 were evaluated. All patients received cetuximab-based first-line
      chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO
      KRK-0104 or AIO KRK-0306 trials. RESULTS: Patients with KRAS codon 12 mutant mCRC
      showed a broad range of outcome when treated with cetuximab-based first-line
      regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong
      trend to a more favorable outcome compared to other mutations (overall survival
      23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model
      illustrated that KRAS p.G12C was associated with unfavorable outcome when treated
      with oxaliplatin plus cetuximab. CONCLUSION: The present analysis suggests that
      KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when
      treated with cetuximab-based first-line therapy.

PMID- 22948723
TI  - Parameter estimation and quantitative parametric linkage analysis with GENEHUNTER
      QMOD.
AB  - OBJECTIVE: We present a parametric method for linkage analysis of quantitative
      phenotypes. The method provides a test for linkage as well as an estimate of
      different phenotype parameters. We have implemented our new method in the program
      GENEHUNTER-QMOD and evaluated its properties by performing simulations. METHODS:
      The phenotype is modeled as a normally distributed variable, with a separate
      distribution for each genotype. Parameter estimates are obtained by maximizing
      the LOD score over the normal distribution parameters with a gradient-based
      optimization called PGRAD method. RESULTS: The PGRAD method has lower power to
      detect linkage than the variance components analysis (VCA) in case of a normal
      distribution and small pedigrees. However, it outperforms the VCA and Haseman
      Elston regression for extended pedigrees, nonrandomly ascertained data and non
      normally distributed phenotypes. Here, the higher power even goes along with
      conservativeness, while the VCA has an inflated type I error. Parameter
      estimation tends to underestimate residual variances but performs better for
      expectation values of the phenotype distributions. CONCLUSION: With GENEHUNTER
      QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes
      in the context of linkage analysis. It is freely available at
      http://www.helmholtz-muenchen.de/genepi/downloads.

PMID- 22948725
TI  - The Human Gene Mutation Database (HGMD) and its exploitation in the fields of
      personalized genomics and molecular evolution.
AB  - The Human Gene Mutation Database (HGMD) constitutes a comprehensive core
      collection of data on germ-line mutations in nuclear genes underlying or
      associated with human inherited disease (http://www.hgmd.org). Data cataloged
      include single-base-pair substitutions in coding, regulatory, and splicing
      relevant regions, micro-deletions and micro-insertions, indels, and triplet
      repeat expansions, as well as gross gene deletions, insertions, duplications, and
      complex rearrangements. Each mutation is entered into HGMD only once, in order to
      avoid confusion between recurrent and identical-by-descent lesions. By March
      2012, the database contained in excess of 123,600 different lesions (HGMD
      Professional release 2012.1) detected in 4,514 different nuclear genes, with new
      entries currently accumulating at a rate in excess of 10,000 per annum. ~6,000 of
      these entries constitute disease-associated and functional polymorphisms. HGMD
      also includes cDNA reference sequences for more than 98% of the listed genes.

PMID- 22948724
TI  - Biomarkers: the next therapeutic hurdle in metastatic renal cell carcinoma.
AB  - Despite recent advances, metastatic renal cell carcinoma remains largely an
      incurable disease. Vascular endothelial growth factor and mammalian target of
      rapamycin inhibitors have provided improvements in clinical outcomes. High-dose
      interleukin 2 remains an option for highly selected patients and is associated
      with durable remissions in a small minority of patients. The toxicity profiles of
      specific agents and patient characteristics and comorbidities and costs have an
      important role in the current choice of therapy. Major challenges encountered in
      developing molecular biomarkers to guide therapy are tumour heterogeneity and
      standardisation of tissue collection and analysis. Although biomarkers are in
      their infancy of development, they should be a priority in early preclinical and
      clinical development in order to guide rational tailored development of emerging
      agents.

PMID- 22948726
TI  - Comparative ncRNA gene and structure prediction using Foldalign and FoldalignM.
AB  - This unit describes how to use Foldalign and FoldalignM to make structural
      alignments of non-protein-coding-RNA (ncRNA). These tools can be used to find new
      ncRNAs, to find the structure of novel ncRNAs, and to improve alignments for
      known ncRNAs.

PMID- 22948727
TI  - Some phenotype association tools in Galaxy: looking for disease SNPs in a full
      genome.
AB  - This unit focuses on some of the tools available on the public Galaxy server that
      are useful for exploring possible associations between human genetic variants and
      phenotypes. We trace step-by-step through an example illustrating several methods
      for examining a single full-coverage genome to look for single-nucleotide
      polymorphisms (SNPs) that are either known to be associated with disease or
      suspected to have impact for other reasons. It makes use of public genomic data,
      tools designed specifically for working with variants, and also some general
      tools for text manipulation and operations on genomic coordinates.

PMID- 22948728
TI  - Genotyping in the cloud with Crossbow.
AB  - Crossbow is a scalable, portable, and automatic cloud computing tool for
      identifying SNPs from high-coverage, short-read resequencing data. It is built on
      Apache Hadoop, an implementation of the MapReduce software framework. Hadoop
      allows Crossbow to distribute read alignment and SNP calling subtasks over a
      cluster of commodity computers. Two robust tools, Bowtie and SOAPsnp, implement
      the fundamental alignment and variant calling operations respectively, and have
      demonstrated capabilities within Crossbow of analyzing approximately one billion
      short reads per hour on a commodity Hadoop cluster with 320 cores. Through
      protocol examples, this unit will demonstrate the use of Crossbow for identifying
      variations in three different operating modes: on a Hadoop cluster, on a single
      computer, and on the Amazon Elastic MapReduce cloud computing service.

PMID- 22948729
TI  - Analyzing protein-protein interactions from affinity purification-mass
      spectrometry data with SAINT.
AB  - Significance Analysis of INTeractome (SAINT) is a software package for scoring
      protein-protein interactions based on label-free quantitative proteomics data
      (e.g., spectral count or intensity) in affinity purification-mass spectrometry
      (AP-MS) experiments. SAINT allows bench scientists to select bona fide
      interactions and remove nonspecific interactions in an unbiased manner. However,
      there is no 'one-size-fits-all' statistical model for every dataset, since the
      experimental design varies across studies. Key variables include the number of
      baits, the number of biological replicates per bait, and control purifications.
      Here we give a detailed account of input data format, control data, selection of
      high-confidence interactions, and visualization of filtered data. We explain
      additional options for customizing the statistical model for optimal filtering in
      specific datasets. We also discuss a graphical user interface of SAINT in
      connection to the LIMS system ProHits, which can be installed as a virtual
      machine on Mac OS X or Windows computers.

PMID- 22948730
TI  - Using ProHits to store, annotate, and analyze affinity purification-mass
      spectrometry (AP-MS) data.
AB  - Affinity purification coupled with mass spectrometry (AP-MS) is a robust
      technique used to identify protein-protein interactions. With recent improvements
      in sample preparation, and dramatic advances in MS instrumentation speed and
      sensitivity, this technique is becoming more widely used throughout the
      scientific community. To meet the needs of research groups both large and small,
      we have developed software solutions for tracking, scoring and analyzing AP-MS
      data. Here, we provide details for the installation and utilization of ProHits, a
      Laboratory Information Management System designed specifically for AP-MS
      interaction proteomics. This protocol explains: (i) how to install the complete
      ProHits system, including modules for the management of mass spectrometry files
      and the analysis of interaction data, and (ii) alternative options for the use of
      pre-existing search results in simpler versions of ProHits, including a virtual
      machine implementation of our ProHits Lite software. We also describe how to use
      the main features of the software to analyze AP-MS data.

PMID- 22948731
TI  - Tuning azolium azolate ionic liquids to promote surface interactions with
      titanium nanoparticles leading to increased passivation and colloidal stability.
AB  - The passivation and stability of suspensions of titanium nanoparticles in azolium
      azolate ionic liquids can be tuned by introducing metal specific binding sites in
      the azolate anion.

PMID- 22948732
TI  - [Aging and quality of life: challenges and opportunities for people with
      intellectual disabilities].
AB  - In the coming years, a growing number of people with an intellectual disability
      will reach retirement age. In line with the change of paradigms, the leading
      ideas of participation, inclusion and self-determination have become the
      principles of the ideological and conceptual framework in social services for
      people with disabilities. However, in many places convincing concepts and
      arrangements of support for elderly people with intellectual disabilities are
      lacking, particularly beyond institutionalized concepts. The research project
      "Lebensqualitat inklusiv(e)" (quality of life included) tries to bridge this gap.
      On the base of an estimation of the demographic development for this group of
      people, models of best practice have been documented and evaluated focusing on
      living conditions and the special requirements for elderly people with
      intellectual disabilities in order to gather ideas for the development of
      arrangements of support. The results show that an interdisciplinary cooperation
      is indispensable.

PMID- 22948733
TI  - Reactions of beta-alkoxyvinyl polyfluoroalkyl ketones with ethyl isocyanoacetate
      and its use for the synthesis of new polyfluoroalkyl pyrroles and pyrrolidines.
AB  - The hitherto unreported reactions of beta-alkoxyvinyl polyfluoroalkyl ketones
      with ethyl isocyanoacetate and equimolar amounts of potassium-tert-butoxide
      proceeded mainly in the beta-position of the alpha,beta-unsaturated ketones in
      cases of alpha-nonsubstituted 1a-e and alpha-methyl substituted ketones 1g-j.
      Other alpha- or beta-substituted ketones 1f,k-o gave mainly products 4 of initial
      attack at the carbonyl carbon. Depending on the solvent, the major products of
      beta-attack do exist in different tautomeric forms. Generally the openchain enol
      tautomers 5 predominate in the polar DMSO-d(6), while the cyclic gamma
      hemiaminals 8 are the major tautomers in the less polar CDCl(3). Acid treatment
      of the latter compounds 8 led to the hitherto unknown ethyl 5-polyfluoroalkyl
      pyrrole-2-carboxylates 11 by elimination of formic acid. Catalytic hydrogenation
      of pyrrole 11a was used for the synthesis of earlier unknown 5-trifluoromethyl
      proline 16.

PMID- 22948734
TI  - Trial history biases the spatial programming of antisaccades.
AB  - The historical context in which saccades are made influences their latency and
      error rates, but less is known about how context influences their spatial
      parameters. We recently described a novel spatial bias for antisaccades, in which
      the endpoints of these responses deviate towards alternative goal locations used
      in the same experimental block, and showed that expectancy (prior probability) is
      at least partly responsible for this 'alternate-goal bias'. In this report we
      asked whether trial history also plays a role. Subjects performed antisaccades to
      a stimulus randomly located on the horizontal meridian, on a 40 degrees  angle
      downwards from the horizontal meridian, or on a 40 degrees  upward angle, with
      all three locations equally probable on any given trial. We found that the
      endpoints of antisaccades were significantly displaced towards the goal location
      of not only the immediately preceding trial (n - 1) but also the penultimate (n -
      2) trial. Furthermore, this bias was mainly present for antisaccades with a short
      latency of <250 ms and was rapidly corrected by secondary saccades. We conclude
      that the location of recent antisaccades biases the spatial programming of
      upcoming antisaccades, that this historical effect persists over many seconds,
      and that it influences mainly rapidly generated eye movements. Because corrective
      saccades eliminate the historical bias, we suggest that the bias arises in
      processes generating the response vector, rather than processes generating the
      perceptual estimate of goal location.

PMID- 22948735
TI  - Magnified visual feedback exacerbates positional variability in older adults due
      to altered modulation of the primary agonist muscle.
AB  - The purpose of this study was to determine whether magnified visual feedback
      during position-holding contractions exacerbates the age-associated differences
      in motor output variability due to changes in the neural activation of the
      agonist muscle in the upper and lower limb. Twelve young (18-35 years) and ten
      older adults (65-85 years) were instructed to accurately match a target position
      at 5 degrees  of index finger abduction and ankle dorsiflexion while lifting 10 %
      of their 1 repetition maximum (1RM) load. Position was maintained at three
      different visual angles (0.1 degrees , 1 degrees , and 4 degrees ) that varied
      across trials. Each trial lasted 25 s and visual feedback of position was removed
      from 15 to 25 s. Positional error was quantified as the root mean square error
      (RMSE) of the subject's performance from the target. Positional variability was
      quantified as the standard deviation of the position data. The neural activation
      of the first dorsal interosseus and tibialis anterior was measured with surface
      electromyography (EMG). Older adults were less accurate compared with young
      adults and the RMSE decreased significantly with an increase in visual gain. As
      expected, and independent of limb, older adults exhibited significantly greater
      positional variability compared with young adults that was exacerbated with
      magnification of visual feedback (1 degrees  and 4 degrees ). This increase in
      variability at the highest magnification of visual feedback was predicted by a
      decrease in power from 12 to 30 Hz of the agonist EMG signal. These findings
      demonstrate that motor control in older adults is impaired by magnified visual
      feedback during positional tasks.

PMID- 22948736
TI  - Project DyAdd: classical eyeblink conditioning in adults with dyslexia and ADHD.
AB  - In this study of the project DyAdd (Adult Dyslexia and Attention Deficit Disorder
      in Finland), classical eyeblink conditioning (EBC) was investigated in both delay
      and trace paradigms in adults (18-55 years) with dyslexia (n = 37), attention
      deficit-hyperactivity disorder (ADHD; n = 21), their comorbid combination (n =
      8), and healthy controls (n = 35). In addition, the profiles of three
      participants with a rare autosomal dominant cerebellar disease were assessed
      (episodic ataxia type 2, EA-2). We found that participants with dyslexia were
      overall slower learners than controls in eyeblink conditioning. Further, they
      were the only group that had a reduced number of CRs in mediotemporal-dependent
      trace paradigm compared to the more cerebellum-dependent delay paradigm. Second,
      ADHD was found to be related to larger CR amplitude. Third, those with a comorbid
      condition learned faster and manifested CRs that were not well timed. Fourth, the
      cerebellar patients showed nearly no conditioning at all. Correlations between
      EBC and various neuropsychological domains (phonological processing, reading,
      spelling, arithmetic, executive functions, attention, and fine motor control)
      over all participants resulted in significant relations only for the delay
      paradigm: Increased amount of reading errors related with later peak latency and
      increased amount of self-corrections in fine motor control related with larger
      response magnitude. Within those who conditioned, relations emerged only for the
      trace paradigm: better spelling was related to larger response magnitude. These
      results do not lend support to the cerebellar hypothesis of dyslexia. On the
      contrary, dyslexia in its pure form seems to be related to a relative dysfunction
      of a larger hippocampal-cerebellar network. Further, larger responses in the ADHD
      group are suggested to result from their lowered responding threshold.

PMID- 22948737
TI  - Perceptual and decisional attenuation of tactile perception during the
      preparation of self- versus externally-generated movements.
AB  - We investigated tactile perception during the execution of self- versus
      externally-generated movements. In a first experiment, we established the
      temporal characteristics of the movements of interest. In a second experiment,
      participants had to try to detect a short gap in an otherwise continuous
      vibratory stimulus delivered to their right wrist under conditions of rest,
      throwing (i.e., self-initiated movement), or catching a basketball (i.e.,
      externally-generated movement). Our hypothesis was that different patterns of
      tactile sensitivity (d') and response bias (criteria c and c') would be observed
      as a function of the timing of gap delivery (i.e., during movement preparation or
      movement execution) and the type of movement (self- or externally-generated). A
      third experiment investigated tactile perception at rest while participants
      adopted different hand postures. This experiment also tested the simple
      preparation of the self-/externally-generated movements versus the observation of
      these targeted movements as performed by the experimenter. Due to sensory
      suppression, participants were significantly less sensitive in detecting the gap
      in tactile stimulation while executing the movement. Preparing to catch the ball
      only triggered a shift in response bias (i.e., participants were more
      liberal/conservative when reporting the gap in stimulation), but no change in
      perceptual sensitivity was observed, as compared to rest. Preparing to make a
      ball-throwing movement resulted in a significant decrement in tactile
      sensitivity, as well as a shift in participants' criterion toward their being
      more conservative, when responding to the presence of the target. Similar
      decrements were observed for the observation of self-initiated movement
      preparation, but not for the observation of their externally-generated
      counterparts. Taken together, these results demonstrate that different forms of
      attenuation influence tactile perception, depending on the type of movement that
      is executed: perceptual and decisional attenuation for self-initiated movements,
      but only decisional attenuation for externally-generated movements. These results
      suggest that the movement preparation sensorimotor contingencies are already
      modulated in prefrontal decision-related cortical brain areas.

PMID- 22948738
TI  - Development of visual and somatosensory attention of the reach-to-eat movement in
      human infants aged 6 to 12 months.
AB  - The reach-to-eat movement is a natural act in which an object or food item is
      grasped and brought to the mouth. It is one of the earliest forelimb behaviours
      displayed by human infants, who bring almost all grasped objects to the mouth,
      and is used daily by adults. In adults, there is a tight coupling between visual
      attention and the advance phase of the reach-to-eat movement. The target is
      visually engaged just as hand advance is initiated and visually disengaged just
      as the target is grasped. This coupling of vision and hand advance suggests that
      advance is mediated by visual attention and withdrawal by somatosensation. The
      present study examined when the tight coupling between visual attention and the
      advance phase of the movement develops in infancy. In a longitudinal study, eight
      infants, aged 6-12 months, and 20 adults reached for familiar inanimate objects
      and food items. Visual gaze, hand movement and hand accuracy were measured using
      frame-by-frame video scoring and 2D kinematic analysis. The study found that the
      youngest infants (6-8 months) visually engaged the target well before initiating
      a reaching movement and continued to fixate on the target after it was grasped
      and as it was brought to the mouth. Between 10 and 12 months of age, infants
      began to visually engage the target just as the reaching movement was initiated
      and visually disengaged the target as it was grasped, as did the adults. Over the
      same developmental time period, the infants developed rotatory hand shaping
      movements, precision grasping, and improved targeting accuracy both for grasping
      the object and placing it into the mouth. The results suggest that visual
      guidance of advance and somatosensory guidance of withdrawal develop together and
      in concert with hand movement ability and skill.

PMID- 22948739
TI  - 18 F-fluorodeoxyglucose uptake predicts pathological complete response after
      neoadjuvant chemotherapy for breast cancer: a retrospective cohort study.
AB  - BACKGROUND AND OBJECTIVES: (18) F-fluorodeoxyglucose ((18) F-FDG) uptake may
      identify poorly differentiated tumors with a high proliferation rate that are
      more responsive to neoadjuvant chemotherapy. METHODS: We retrospectively
      evaluated 273 patients (mean age, 44.2 years; range 23-78 years) newly diagnosed
      with stage II or III invasive ductal breast cancer between 2006 and 2010. All
      patients were treated with neoadjuvant chemotherapy followed by surgery. The
      ability of parameters to predict pathological complete response (pCR), was
      assessed by multivariate analysis. RESULTS: Of the 273 breast cancer patients, 30
      (11.0%) achieved pCR. Univariate analysis revealed that higher histologic grade
      (P < 0.001), lack of estrogen receptor (ER, P < 0.001); and a higher maximal
      standardized uptake value (SUVmax, P < 0.001) were associated with pCR, whereas
      HER2/neu amplification and Ki-67 expression were not (P > 0.05 for each
      comparison). Multivariate analysis showed that negative ER (odds ratio [OR] =
      9.98; 95% confidence interval [CI], 2.88-34.52, P < 0.001) and the SUVmax of (18)
      F-FDG uptake (OR per one unit increase in SUVmax = 1.09; 95% CI, 1.02-1.16, P =
      0.008) were independent predictors of pCR. CONCLUSIONS: ER status and (18) F-FDG
      uptake are independent predictors of pCR after neoadjuvant chemotherapy for
      breast cancer.

PMID- 22948740
TI  - Morphology analysis of vertebral trabecular bone under dynamic loading based on
      multi-scale theory.
AB  - Trabecular bone has a complicated porous microstructure and consists of
      interconnected plates and rods known as trabeculae. The microarchitecture of the
      trabeculae contributes to load distribution capacity and, particularly, the
      optimal bone strength. Many previous studies have shown that morphological
      parameters are used to characterize the microarchitecture of trabecular bone, but
      little is known about the mechanical role of trabecular morphology in the context
      of load-bearing behavior. Therefore, this study proposes a new segmentation
      method for examining the morphology of trabecular structure foci of load-bearing
      capability. A micro-finite element model of trabecular bone was obtained from the
      fourth lumbar vertebra on the basis of a three-dimensionally reconstructed micro
      computed tomography (CT) image. We used an asymptotic homogenization method to
      determine microscopic stress by applying three unidirectional compressive loads
      in the vertical, anteroposterior, and right-left axes of two trabecular bone
      volumes. We then classified the complicated trabecular microstructure into three
      segments: primary and secondary trabeculae and trabeculae of no contribution.
      Next, a dynamic analysis was conducted by applying a force impulse load. The
      result indicated that 1/3 of the trabecular volume functions as primary
      trabecula. The morphology of the trabecular network could be visualized
      successfully highlighting the percolation of the stress wave in the primary
      trabecular segment. Further, we found that the role of the plate-like structures
      was that of a hub in the trabecular network system.

PMID- 22948742
TI  - Combination of IL-1 receptor antagonist, IL-20 and CD40 ligand for the prediction
      of acute cellular renal allograft rejection.
AB  - PURPOSE: The outcome of renal transplantation is difficult to predict, even with
      an allograft biopsy. The aim of this study was to develop a sensitive, specific
      and noninvasive method for prediction of acute cellular rejection (ACR). METHODS:
      Luminex analysis was used to determine the levels of 95 cytokines/chemokines and
      their soluble receptors in sera from recipients with: ACR (in the first month
      post-transplantation, before and during rejection, and after rejection reversal);
      stable allograft function; delayed graft function (DGF); pulmonary infection.
      Evaluation of significant differential protein expression in ACR patients
      compared with stable allograft controls revealed a three-analyte combination as a
      marker of renal transplantation outcome. The predictive value of this combination
      was further validated in DGF and infection groups and in a blind binary code
      study of 24 additional serum samples. RESULTS: Significant differential
      expression was detected in 26 proteins expressed in patients during the period
      preceding an ACR episode compared with stable controls. A blood test for
      discrimination of such patients was developed based on the simultaneous
      quantification of three analytes (IL-1 receptor antagonist, IL-20 and sCD40
      ligand). This test exhibited 90.9 % sensitivity, 96 % specificity, a positive
      predictive value (PPV) of 95.2 % and a negative predictive value (NPV) of 92.3 %.
      Moreover, this combination allowed discrimination between patients with ACR and
      DGF and pulmonary infection. CONCLUSIONS: With further development and
      validation, this blood test can be used to predict ACR and direct the treatment
      of transplant patients in the clinic.

PMID- 22948741
TI  - The immunologic functions of the neonatal Fc receptor for IgG.
AB  - Careful regulation of the body's immunoglobulin G (IgG) and albumin
      concentrations is necessitated by the importance of their respective functions.
      As such, the neonatal Fc receptor (FcRn), as a single receptor, is capable of
      regulating both of these molecules and has become an important focus of
      investigation. In addition to these essential protection functions, FcRn
      possesses a number of other functions that are equally as critical and are
      increasingly coming to attention. During the very first stages of life, FcRn
      mediates the passive transfer of IgG from mother to offspring both before and
      after birth. In the adult, FcRn regulates the persistence of both IgG and albumin
      in the serum as well as the movement of IgG, and any bound cargo, between
      different compartments of the body via transcytosis across polarized cells. FcRn
      is also expressed by hematopoietic cells; consistent with this, FcRn regulates
      MHC class II presentation and MHC class I cross-presentation by dendritic cells.
      As such, FcRn plays an important role in immune surveillance throughout adult
      life. The increasing appreciation for FcRn in both homeostatic and pathological
      conditions is generating an intense interest in the potential for therapeutic
      modulation of FcRn binding to IgG and albumin.

PMID- 22948743
TI  - The ex vivo production of IL-6 and IL-21 by CD4+ T cells is directly associated
      with neurological disability in neuromyelitis optica patients.
AB  - Neuromyelitis optica (NMO), also known as Devic's disease, is an autoimmune,
      inflammatory disorder of the central nervous system (CNS) in which the immune
      system attacks myelin of the neurons located at the optic nerves and spinal cord,
      thus producing a simultaneous or sequential optic neuritis and myelitis. The
      objective of this study was evaluated the background T-cell function of patients
      suffering from neuromyelitis optica (NMO), an autoimmune disorder of the central
      nervous system. In our study, the in vitro T cell proliferation and the
      production of Th1 cytokines were significantly lower in cell cultures from NMO
      patients, as compared with healthy individuals. In contrast, a dominant Th17-like
      phenotype, associate with higher IL-23 and IL-6 production by LPS-activated
      monocytes, was observed among NMO patients. The release of IL-21 and IL-6 by
      polyclonally activated CD4+ T cells was directly correlated to neurological
      disability. In addition, the in vitro release of IL-21, IL-6 and IL-17 was
      significantly more resistant to glucocorticoid inhibition in NMO patients. In
      conclusion, the results indicate dominant Th17-related response in NMO patients
      that was directly proportional to neurological disability. Furthermore, our
      results can help to explain why NMO patients trend to be more refractory to
      corticoid treatment.

PMID- 22948744
TI  - Of mice and men: the need for humanized mouse models to study human IgG activity
      in vivo.
AB  - Antibodies of the IgG isotype have a variety of pro- and anti-inflammatory
      effector functions, making them attractive platforms for the development of novel
      therapeutic approaches. Animal model systems have been invaluable to the
      understanding of the underlying mechanisms of IgG activity. However, differences
      in the IgG subclasses and Fc receptors responsible for mediating IgG-dependent
      effector functions, even between such closely related species as humans and
      monkeys, make it difficult to predict the activity of human IgG in vivo. This
      review will focus on currently available animal model systems used to study human
      IgG activity and will propose novel model systems that might enable us to obtain
      a closer look at the molecular and cellular mechanisms underlying human IgG
      activity in vivo.

PMID- 22948745
TI  - Hepatitis B virus X protein plays an important role in gastric ulcers.
AB  - Hepatitis B virus (HBV) infects many individuals globally each year. Researchers
      usually focus on the relationship between HBV and liver diseases. In this study,
      we investigated the effects of HBV infection on gastric mucosa. We detected the
      levels of HBX protein and mRNA in specimens from sixty-four chronic hepatitis B
      patients (CHB) with gastric ulcers. We confirmed that HBX could aggravate gastric
      ulcers according to clinicopathological parameters. In addition, we constructed
      the pcDNA3.1-HBX plasmid and transfected it into GES-1, a gastric mucosal cell
      line. The results indicated that HBX could induce apoptosis and G1 arrest in GES
      1 cells. Insights into the mechanism of HBX action in GES-1 cells were obtained
      using western blot analysis.

PMID- 22948746
TI  - Frontal transcortical approach in 12 central neurocytomas.
AB  - BACKGROUND: Central neurocytomas (CN) are rare intraventricular tumors with
      benign clinical behavior that typically affect young adults. Although a favorable
      prognosis is generally expected after adequate management, there is no general
      consensus on the standard of therapy. We evaluated the efficacy and safety of
      radical surgery for the management of CN. METHODS: Between 1996 and 2010, 12
      patients with CN (eight males and four females; range, 18 to 62 years; mean age,
      28.5 years) were surgically treated in our institution. The initial goal of
      therapy was complete resection through a frontal transcortical approach, and
      repeat surgery was done in cases of residual or recurrent disease. The mean
      follow-up period was 51.2 months (range, 14-149 months). RESULTS: Complete
      resection was achieved in all patients either with primary (nine patients, 75 %)
      or second-look surgery (three patients, 25 %). No mortalities occurred and there
      were four surgery-related complications (two events of transient hemiparesis, one
      transient aphasia, and onepostoperative subdural hygroma). All patients were
      alive with normal activities of daily living at the last follow-up. Two patients
      (16.6 %) experienced a single recurrence at 26 and 66 months, one of whom
      underwent redo-surgery. CONCLUSION: For the management of CN, complete resection
      is feasible, effective, and safe. Repeat surgery may be a viable option in cases
      of residual or recurrent disease and the use of radiotherapy can be avoided in
      this young population.

PMID- 22948747
TI  - Assessing the functional status of the motor system in brain tumor patients using
      transcranial magnetic stimulation.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is being used in the pre
      operative diagnostics of patients with tumors in or near the motor cortex.
      Although the main purpose of TMS in such patients is to map the functional areas
      of the motor cortex in spatial relation to the tumor, TMS also provides some
      numerical neurophysiological measurements of the functional status of the
      patient's motor system. The aim of this paper is to provide reference values for
      these neurophysiological measurements from a large and varied clinical sample.
      METHODS: TMS was used in the pre-operative work-up of patients with various types
      of tumors in or near the motor cortex during a 3-year period. Data was collected
      prospectively in 100 patients, yet this is a post hoc report. RESULTS: Patient
      characteristics had no influence on the neurophysiological parameters. The
      response latency time was almost never different in the tumorous versus healthy
      hemisphere, so clinicians should be suspicious if they find interhemispheric
      differences for latency. A high interhemispheric ratio of resting motor threshold
      (RMT) or a low interhemispheric ratio of motor evoked potential (MEP) amplitude
      appear to suggest immanent deterioration of the patient's motor status.
      CONCLUSION: In addition to topographic cortical mapping, TMS also serves as a
      neurophysiological assessment of the functional status of the patient's motor
      system. The results presented here provide clinicians with a set of reference
      values to contextualize findings in their own tumor patients. Further research is
      still needed to better understand the full clinical relevance of these
      neurophysiological parameters.

PMID- 22948748
TI  - Decreased hypoxia-inducible factor-1alpha in gastrocnemius muscle in rats with
      chronic kidney disease.
AB  - BACKGROUND/AIMS: Hypoxia-inducible factor (HIF)-1alpha is responsible for
      increased expression of genes engaged in angiogenesis. Our previous study
      indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in
      locomotor muscles of uremic animals. Perhaps these changes are secondary to
      disturbances of HIF-1alpha in skeletal muscles. METHODS: Expression of HIF-1alpha
      at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor
      A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2,
      endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase
      (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were
      measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy
      (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls). RESULTS: For
      CKD5/6 versus controls, mRNA levels for HIF-1alpha, VEGF-A, VEGFR-1 and VEGFR-2
      were significantly reduced only in MG, while eNOS was significantly decreased and
      iNOS was significantly increased only in ML. Western blot analysis indicated
      significantly increased HIF-1alpha protein levels in MG and ML from CKD1/2
      animals versus controls, whereas in the CKD5/6 group, the level of HIF-1alpha
      protein decreased significantly in MG and increased significantly in ML versus
      controls and CKD1/2. CONCLUSION: The reduced expression of HIF-1alpha mRNA and
      protein in locomotor muscle from CKD5/6 animals may be involved in the
      pathogenesis of uremic myopathy. Increased expression of iNOS in the postural
      muscles may act as a protective factor through HIF-1alpha stabilization.

PMID- 22948749
TI  - The search for secreted proteins in prostate cancer by the Escherichia coli
      ampicillin secretion trap: expression of NBL1 is highly restricted to the
      prostate and is related to cancer progression.
AB  - AIMS: Genes expressed only in cancer tissue or specific organs will be useful
      molecular markers. To identify genes that encode secreted proteins present in
      prostate cancer (PCa), we generated Escherichia coli ampicillin secretion trap
      (CAST) libraries from PCa and normal prostate (NP). METHODS AND RESULTS: We
      identified 15 candidate genes that encode secreted proteins present in PCa and
      NP. Quantitative RT-PCR analysis revealed that MSMB, NBL1 and AZGP1 were
      expressed with much higher specificity in PCa and NP than in 14 other kinds of
      normal tissue. We focused on NBL1, which was originally identified as a putative
      tumor suppressor gene. Western blot analysis revealed that NBL1 protein was
      highly expressed in both cell lysate and culture media of the DU145 PCa cell
      line. Immunohistochemical analysis showed that NBL1 expression was highly
      detected in and restricted to NP and PCa and was significantly down-regulated in
      PCa. NBL1 expression was significantly reduced according to the tumor stage,
      Gleason grade and preoperative prostate-specific antigen (PSA) value. CONCLUSION:
      NBL1 is a secreted protein that is highly restricted to the prostate.
      Underexpression of NBL1 correlated with PCa progression. NBL1 might be a
      candidate tumor marker for PCa in addition to PSA.

PMID- 22948750
TI  - Hypertrophic (verrucous) cutaneous lupus erythematosus of the lip and oral
      cavity: a series of 4 cases.

PMID- 22948751
TI  - Pt-Pd alloy nanoparticle-decorated carbon nanotubes: a durable and methanol
      tolerant oxygen reduction electrocatalyst.
AB  - We describe the decoration of multiwalled carbon nanotubes (MCNTs) with Pt-Pd
      alloy nanoelectrocatalysts of three different compositions and their
      electrocatalytic performance toward the oxygen reduction reaction (ORR). The
      decoration of the MCNTs involves polymer-assisted impregnation of metal
      precursors PtCl(6)(2-) and PdCl(6)(2-) and the subsequent reduction of the
      impregnated precursors by a modified polyol route. The composition of the
      catalyst was controlled by tuning the molar ratio of the precursors during their
      impregnation. Electron probe microscopic analysis shows that the catalysts have
      compositions of Pt(46)Pd(54,) Pt(64)Pd(36) and Pt(28)Pd(72). The Pt(46)Pd(54) and
      Pt(64)Pd(36) catalysts have truncated octahedral and icosahedral shapes with a
      size ranging from 8 to 10 nm. On the other hand, the catalyst of Pt(28)Pd(72)
      composition has a spherical/quasispherical shape with a size distribution of 1-2
      nm. The XPS measurement confirms the signature of metallic Pt and Pd. The
      Pt(46)Pd(54) catalyst has a pronounced electrocatalytic activity toward the ORR
      with a specific and mass activity of 378 MUA cm(Pt-Pd)(-2) and 64 MUA MUg(Pt-Pd)(
      1), respectively at 0.8 V. Moreover, the Pt(46)Pd(54) nanoelectrocatalyst is
      highly durable and it retains its initial catalytic activity even after 1000
      extensive cycles. Interestingly, this catalyst has a very high tolerance toward
      methanol and it does not favor the oxidation of methanol in the potential window
      of 0.1-1.4 V. The electrocatalytic activity of the alloy electrocatalyst is
      compared with commercially available Pt black and MCNT-supported spherical Pt
      nanoparticles. The catalytic activity of the Pt(46)Pd(54) nanoelectrocatalyst is
      higher than the other catalysts. The Pt(46)Pd(54) catalyst outperforms the
      electrocatalytic activity of all other catalysts.

PMID- 22948752
TI  - Cell fate conversion: direct induction of hepatocyte-like cells from fibroblasts.
AB  - One of the essential features of stem cells is their cellular plasticity to
      differentiate into daughter cells with defined functions. Recently, induction of
      pluripotent stem cells from somatic cells by defined transcription factors led to
      the focus on cellular plasticity of terminally differentiated cells. This
      approach is adopted by other studies to demonstrate the cell fate conversion
      between different lineages of terminally differentiated cells. We and others
      showed that induced hepatocyte-like (iHep) cells are directly converted from
      mouse fibroblasts by overexpression of liver-enriched transcription factors. iHep
      cells as well as pluripotent stem cell- or mesenchymal stem cell-derived
      hepatocyte-like cells provide potential cell sources for disease modeling,
      transplantation, and tissue engineering independent of donor organs. Here, we
      review the latest advances in generating hepatocyte-like cells and summarize
      general criteria for evaluating these cells. In addition, we propose a possible
      role of the p19(Arf) /p53 pathway in cell fate maintenance, which apparently
      limits the formation of induced pluripotent stem (iPS) cells and iHep cells.

PMID- 22948753
TI  - Numerical assessment of the performance of a scalp-implantable antenna: effects
      of head anatomy and dielectric parameters.
AB  - We numerically assess the effects of head properties (anatomy and dielectric
      parameters) on the performance of a scalp-implantable antenna for telemetry in
      the Medical Implant Communications Service band (402.0-405.0 MHz). Safety issues
      and performance (resonance, radiation) are analyzed for an experimentally
      validated implantable antenna (volume of 203.6 mm(3) ), considering five head
      models (3- and 5-layer spherical, 6-, 10-, and 13-tissue anatomical) and seven
      scenarios (variations +/- 20% in the reference permittivity and conductivity
      values). Simulations are carried out at 403.5 MHz using the finite-difference
      time-domain method. Anatomy of the head model around the implantation site is
      found to mainly affect antenna performance, whereas overall tissue anatomy and
      dielectric parameters are less significant. Compared to the reference dielectric
      parameter scenario within the 3-layer spherical head, maximum variations of 
      19.9%, +3.7%, -55.1%, and -39.2% are computed in the maximum allowable net input
      power imposed by the IEEE Std C95.1-1999 and Std C95.1-2005 safety guidelines,
      return loss, and maximum far-field gain, respectively. Compliance with the recent
      IEEE Std C95.1-2005 is found to be almost insensitive to head properties, in
      contrast with IEEE Std C95.1-1999. Taking tissue property uncertainties into
      account is highlighted as crucial for implantable antenna design and performance
      assessment. Bioelectromagnetics 34:167-179, 2013. (c) 2012 Wiley Periodicals,
      Inc.

PMID- 22948754
TI  - Serum osteocalcin is not associated with glucose but is inversely associated with
      leptin across generations of nondiabetic women.
AB  - CONTEXT: The skeleton is recognized as an important player in energy metabolism
      through its interactions with other tissues. Whether the association of
      osteocalcin with glucose metabolism is age dependent has not been fully
      addressed. OBJECTIVE: The objective of the study was to examine the age-specific
      association between different forms of osteocalcin and glucose and adipokines.
      DESIGN: This was a family-based study across three generations. SETTING: The
      study was conducted at a university laboratory. PARTICIPANTS: Sixty-four daughter
      premenopausal mother-maternal grandmother trios participated in the study.
      METHODS: Fasting plasma glucose and insulin concentrations, serum total (tOC),
      carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin,
      and adiponectin levels, and fat masses were assessed. Generalized estimating
      equations (GEE) model was used to assess the associations of bone biomarkers with
      glucose metabolism variables and adipokines. RESULTS: No significant difference
      in insulin was found between generations, whereas glucose and leptin increased
      with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in
      mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers
      and girls. Despite the differences in insulin and glucose between the low and
      high homeostasis model assessment insulin resistance index (HOMA-IR) groups
      within generations, no significant differences in tOC, cOC, and ucOC were found.
      Compared with their low HOMA-IR counterparts, the high HOMA-IR group had
      significantly higher leptin and lower adiponectin in mothers and grandmothers.
      The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or
      adiponectin when the three generations were evaluated together, but when
      separated by generation, leptin was inversely correlated with tOC (P = 0.003) and
      cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042).
      CONCLUSIONS: Osteocalcin, glucose, and adipokines change with age but in a
      noncommensurate manner. We infer that the association between osteocalcin and
      glucose metabolism is minor and age specific in nondiabetic women. Leptin,
      however, strongly correlated with insulin resistance independently of fat masses,
      suggesting that obesity, as a metabolic disorder risk factor, affects glucose
      metabolism, partly through the role of leptin.

PMID- 22948755
TI  - Thyroglobulin autoantibodies in patients with papillary thyroid carcinoma:
      comparison of different assays and evaluation of causes of discrepancies.
AB  - CONTEXT: Thyroglobulin autoantibodies (TgAb) have been proposed as a surrogate
      marker of thyroglobulin in the follow-up of differentiated thyroid carcinoma.
      Commercially available TgAb assays are often discordant. We investigated the
      causes of discrepancy. DESIGN: TgAb were measured by three noncompetitive
      immunometric assays and three competitive RIA in 72 patients with papillary
      thyroid carcinoma and associated lymphocytic thyroiditis (PTC-T), 105 with
      papillary thyroid carcinoma and no lymphocytic thyroiditis (PTC), 160 with
      Hashimoto's thyroiditis, and in 150 normal subjects. The results of the six
      assays were correlated. TgAb epitope pattern, evaluated by inhibition of serum
      TgAb binding to thyroglobulin by TgAb-Fab regions A, B, C, and D, were compared
      in sera which were positive in all six assays (concordant sera) and positive in
      only one to five assays (discordant sera) were compared. TgAb International
      Reference Preparation (IRP) was measured in 2007 and 2009. RESULTS: The
      correlations of the six assays ranged from -0.01 to 0.93 and were higher in PTC-T
      and Hashimoto's thyroiditis than in PTC and normal subjects. Two uncorrelated
      components, one including the three immunometric assays, the other the three RIA,
      explained 40 and 37% of the total variance of the results of the six assays. The
      levels of inhibition were higher in concordant sera than in discordant sera by
      TgAb-Fab region B (27.0%, 21.2-34.0 vs. 6.0%, and 2.7-12.7%) and region C (30.5%,
      21.3-37.7 vs. 4.0%, and 1.0-6.5%); thus, the epitope pattern was more homogeneous
      in concordant sera than in discordant sera. TgAb IRP ranged from 157 to 1088
      (expected 1000) IU/ml in 2009; results in 2007 were similar in all but two
      assays. CONCLUSIONS: TgAb assays are highly discordant. Discrepancy is lower when
      comparing assays with similar methodology. Results of TgAb from PTC-T are more
      concordant than those from PTC because their epitope pattern is more restricted.
      The internal standardization of TgAb is generally, but not completely,
      satisfactory.

PMID- 22948756
TI  - Insights into puberty: the relationship between sleep stages and pulsatile LH
      secretion.
AB  - CONTEXT: During the pubertal transition, LH secretion initially increases only
      during sleep; however, its relationship to sleep stage is unknown. OBJECTIVES:
      Our objective was to determine whether the initiation of LH pulses is related to
      a specific sleep stage in pubertal children. DESIGN AND SETTING: Frequent blood
      sampling and polysomnographic studies were performed in a Clinical Research
      Center. SUBJECTS: Fourteen studies were performed in nine healthy pubertal
      children, ages 9.9-15.6 yr. INTERVENTIONS: Subjects underwent one to two
      overnight studies with polysomnography and blood sampling for LH at 10-min
      intervals. RESULTS: Alignment of polysomnographic records and LH pulses
      demonstrated that LH pulses (n = 58) occurred most frequently during slow-wave
      sleep (SWS) (1.1 pulse/h, n = 30) compared with all other sleep stages or periods
      of wake after sleep onset (P < 0.001). There was also a significant increase in
      the amount of SWS in the 15 min preceding and the 5 min following each pulse
      compared with the amount of SWS seen across the study night (P < 0.01).
      CONCLUSIONS: During puberty, the majority of LH pulses that occur after sleep
      onset are preceded by SWS, suggesting that SWS is intimately involved in the
      complex control of pubertal onset. These studies raise concerns about the
      potential hormonal repercussions of the increasing prevalence of sleep
      disturbances in adolescents.

PMID- 22948757
TI  - Expression of the ring ligase PRAJA2 in thyroid cancer.
AB  - INTRODUCTION: In thyroid cells, binding of TSH to its receptor increases cAMP
      levels, sustaining thyrocytes growth and hormone production. The main cAMP
      effector enzyme is protein kinase A (PKA). Praja2 is a widely expressed RING
      (Really Interesting New Gene) ligase, which degrades the regulatory subunits of
      PKA, thus controlling the strength and duration of PKA signaling in response to
      cAMP. Differentiated thyroid cancer expresses a functional TSH receptor, and its
      growth and progression are positively regulated by TSH and cAMP signaling. AIM:
      We aimed to analyze the expression of praja2 in a group of 36 papillary thyroid
      cancer (PTC), 14 benign nodules, and six anaplastic thyroid cancers (ATC).
      METHODS: We measured praja2 mRNA levels by quantitative RT-PCR and praja2
      expression by Western blot and immunohistochemistry. Possible association between
      praja2 mRNA and the presence of known mutations was evaluated. RESULTS: We found
      a statistical significant increase of mRNA levels in PTC tissue samples, compared
      with benign nodules and ATC. In particular, mRNA levels were maximal in
      differentiated thyroid cancer (PTC), progressively decreasing in more aggressive
      tumors, ATC having the lowest amount of praja2 mRNA. Accordingly, higher levels
      of praja2 protein were detected in lysates from PTC, compared with ATC. By
      immunohistochemistry, in PTC sections we observed a marked increase of
      cytoplasmic praja2 signal, which significantly decreased in less differentiated
      thyroid tumors, completely disappearing in ATC. Studies in cultured cells stably
      expressing RET/PTC1 oncogene or mutant BRAF revealed a direct correlation between
      praja2 mRNA levels and malignant phenotype of transformed cells. Similar results
      were obtained using thyroid cancer tissues carrying the same mutations.
      CONCLUSIONS: praja2 is markedly overexpressed in differentiated thyroid cancer,
      and its levels inversely correlate with the malignant phenotype of the tumor.
      Thus, praja2 is a novel cancer-related gene whose expression is linked to the
      histotype and mutational status of the thyroid tumor.

PMID- 22948758
TI  - Differential effect of insulin like growth factor-I on constriction of human
      uterine and placental arteries.
AB  - CONTEXT: Discrete regulation of the uterine and placental vasculatures is an
      important feature of uteroplacental perfusion and pregnancy success because
      appropriate maternal/fetal exchange of nutrients and gases is crucial for normal
      fetal growth. Placental vasculature lacks autonomic innervation so tone is
      controlled by locally derived vasoactive factors. IGF-I, which is produced by the
      placenta, is critical for normal fetal growth and studies of animal vascular
      systems have shown that IGF-I regulates vasomotor tone. OBJECTIVE: The objective
      of the study was to determine whether IGF-I directly alters human placental and
      myometrial arterial tone in vitro. PARTICIPANTS: Women with uncomplicated
      pregnancy delivering a singleton infant at term participated in the study.
      SETTING: The study was conducted at university hospital laboratories. MAIN
      OUTCOME MEASURE(S): Comparison of arterial tension measured before and after
      exposure to IGF-I. DESIGN: Placental and myometrial arteries were mounted on a
      wire myograph, exposed to the constrictor U46619 (10(-10) to 10(-5) m), returned
      to baseline tension, and then incubated with IGF-I (0-500 ng/ml) for various time
      points before performing a second dose-response curve to U46619. IGF-I receptor
      protein expression was assessed. RESULTS: IGF-I did not acutely alter the
      response of placental arteries to U46619. Exposure of myometrial arteries to IGF
      I caused a rightward shift of U46619 dose-response curves (P < 0.05); EC(50) data
      were significantly increased at 30 (15.5 +/- 2.8 vs. 133 +/- 44 nm, before and
      after IGF treatment, respectively) and 60 min (10.9 +/- 1.9 vs. 146 +/- 47 nm).
      Placental and myometrial arteries had a similar IGF-I receptor expression
      profile. CONCLUSIONS: IGF-I acutely modulates the vasomotor tone of human
      myometrial, but not placental, arteries, suggesting that IGF-I regulates the
      delivery of maternal blood to the placenta.

PMID- 22948759
TI  - Maternal pregravid weight is the primary determinant of serum leptin and its
      metabolic associations in pregnancy, irrespective of gestational glucose
      tolerance status.
AB  - CONTEXT: Several previous studies have investigated circulating levels of the
      adipokine leptin in relation to gestational diabetes mellitus (GDM). However,
      these studies have yielded markedly conflicting results, including increased,
      decreased, and unchanged leptin levels in women with GDM as compared with their
      peers. OBJECTIVE: We sought to evaluate the metabolic determinants of serum
      leptin in a well-characterized cohort reflecting the full spectrum of glucose
      intolerance in pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Metabolic
      characterization, including oral glucose tolerance test (OGTT) and measurement of
      serum leptin, insulin, lipids, adiponectin, and C-reactive protein, was performed
      in 817 pregnant women. The OGTT identified 198 women with GDM, 142 with
      gestational impaired glucose tolerance, and 477 with normal glucose tolerance.
      RESULTS: Median leptin (ng/ml) did not differ between the normal glucose
      tolerance (33.7), gestational impaired glucose tolerance (36.3), and GDM (36.4)
      groups (P = 0.085). On univariate correlation analysis, leptin was most strongly
      associated with prepregnancy body mass index (BMI) (r = 0.54, P < 0.0001),
      fasting insulin (r = 0.60, P < 0.0001), and C-reactive protein (r = 0.38, P <
      0.0001) but only weakly associated with area under the glucose curve
      (AUC(glucose)) on the OGTT (r = 0.10, P = 0.0066). On multiple linear regression
      analysis, the strongest independent determinant of leptin was prepregnancy BMI (t
      = 11.55, P < 0.0001), whereas AUC(glucose) was not a significant predictor (t = 
      0.95, P = 0.34). Furthermore, although its respective associations with fasting
      insulin, triglycerides, and adiponectin varied across tertiles of prepregnancy
      BMI, leptin was not significantly associated with AUC(glucose) in any BMI
      tertile. CONCLUSIONS: Pregravid BMI, rather than gestational glucose tolerance,
      is the primary determinant of serum leptin concentration in pregnancy.

PMID- 22948760
TI  - Fractures in healthy females followed from childhood to early adulthood are
      associated with later menarcheal age and with impaired bone microstructure at
      peak bone mass.
AB  - BACKGROUND: Whether fractures observed in healthy children are associated with
      microstructural alterations and strength deficit that persists by the end of the
      growth period is not established. Considering the importance of pubertal timing
      in bone development, we also quantified the fracture risk related to later
      menarcheal age (MENA). PARTICIPANTS AND METHODS: We followed 124 healthy girls
      from mean +/- sd age 7.9 +/- 0.5 to 20.4 +/- 0.6 yr. Fractures, MENA, and radius
      areal bone mineral density (aBMD) were recorded at regular intervals. At a mean
      age of 20.4 yr, microstructural and strength variables of the distal radius were
      determined by high-resolution peripheral computerized tomography and micro-finite
      element analysis. RESULTS: Sixty-one fractures occurred in 42 subjects. At 20.4
      yr, subjects with fractures had lower aBMD at radial diaphysis (P = 0.005) and
      metaphysis (P = 0.008), lower distal radius trabecular volumetric density (vBMD)
      (P = 0.010) and thickness (P = 0.014), and reduction in stiffness (P = 0.013),
      failure load (P = 0.013), and apparent modulus (P = 0.046). Odds ratios revealed
      an increased risk of fracture for a 1-sd reduction in radial aBMD diaphysis [1.97
      (P = 0.006)] and metaphysis [1.97 (P = 0.008)] and distal radius trabecular vBMD
      [1.89 (P = 0.011)], thickness [1.97 (P = 0.017)], stiffness [2.02 (P = 0.014)],
      failure load [2.00 (P = 0.014)], and apparent modulus [1.79 (P = 0.043)]. MENA
      occurred at a later age in subjects with fractures (P = 0.003). For MENA 1 sd
      (1.2 yr) later, the increase of fracture risk was 2.1 (P = 0.002). CONCLUSIONS:
      In healthy young women, low trabecular vBMD and thickness in the distal radius
      are associated with reduced bone strength and increased fracture risk during
      growth. This study also documents that later pubertal timing is associated with
      increased incidence of fracture during childhood and adolescence.

PMID- 22948761
TI  - Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid
      disease.
AB  - CONTEXT: Fetuses from mothers with autoimmune thyroid disease (AITD) may be
      affected by antithyroid antibodies, antithyroid drugs, and iodine. OBJECTIVE: The
      study correlated fetal free T(4) (fT4) with fetal ultrasound parameters and
      maternal thyroid function, thyroid antibodies, and medication dose from mothers
      with AITD. DESIGN AND SETTING: The study was designed as a prospective cohort
      study and conducted in an academic referral center. PATIENTS: Eighty-three of 85
      women with AITD completed the study; 38 were treated for hyperthyroidism and 25
      for hypothyroidism, and 20 were euthyroid. MAIN OUTCOME MEASURES: Outcomes were
      as follows: 1) fetal-fT4, TSH, ultrasound parameters (morphology, biometrics,
      heart rate); and 2) maternal-fT4, TSH, antithyroid drug dose, and antithyroid
      antibodies, thyroid peroxidase and TSH receptor (TRAK). Parameters were
      determined at the same time, between the 22nd and 33rd wk gestation. RESULTS: A
      total of 48.3% of fetuses from hyperthyroid mothers, 60% of fetuses from
      hypothyroid mothers, and 10% of fetuses from euthyroid mothers had elevated fT4
      levels (P = 0.006). In hypothyroid mothers, the presence of both thyroid
      antibodies was related to fetal hyperthyroidism, whereas absence was related to
      fetal euthyroidism (P = 0.019). Hyperthyroid mothers (TRAK-positive, thyroid
      peroxidase-negative) with hyperthyroid fetuses had significantly higher mean TRAK
      than hyperthyroid mothers with euthyroid fetuses (13.7 vs. 3.7 IU/liter; P =
      0.02). Fetal fT4 correlated weakly negatively with maternal TSH within the normal
      range, but not with ultrasound parameters or with antithyroid drug dose.
      CONCLUSION: High fetal fT4 levels were unexpectedly frequent in women with AITD,
      including maternal autoimmune hypo- and hyperthyroidism. Further studies are
      needed, as well as noninvasive methods to assess fetal thyroid function.

PMID- 22948762
TI  - Alterations of circulating endothelial cell and endothelial progenitor cell
      counts around the ovulation.
AB  - CONTEXT: Circulating endothelial cells (CECs) and progenitor cells (CEPs) have
      been intensively studied as a promising tool for treating ischemic diseases and
      monitoring cancer treatments, but how the menstrual cycle affects the variation
      in their counts remains unclear. OBJECTIVE: The aims of the study were to
      determine the influence of the menstrual cycle on the number of CECs and CEPs and
      to investigate the association of their counts with circulating hormones and
      angiogenesis-associated factors. DESIGN: CEP and CEC counts by flow cytometry and
      the CellSearch system and circulating factor levels were measured eight times
      during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into
      six phases based on hormone concentrations. RESULTS: CEP counts peaked in the
      periovulatory and middle luteal phases with a drop in the early luteal phase. CEC
      counts showed no significant variation. There were significant correlations
      between the CEP counts and the serum concentrations of estradiol (E2), LH, and
      granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P =
      0.01, respectively). The difference in CEP counts between two adjacent phases was
      significantly correlated with that in E2, LH, G-CSF, and serum vascular
      endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006,
      respectively). CONCLUSION: CEP counts peaked in the periovulatory and middle
      luteal phases, with a drop in the early luteal phase, and were correlated with
      serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP
      counts would be important for the clinical application of CEPs.

PMID- 22948763
TI  - Screening of turner syndrome with novel auxological criteria facilitates early
      diagnosis.
AB  - CONTEXT: Screening criteria for abnormal growth in children are traditionally
      based on height-for-age, height distance from target height (TH), and change in
      growth rate. However, there is no consensus on the optimal screening limits.
      OBJECTIVE: Our objective was to first develop new population-based and age
      specific cutoffs for these three screening parameters and, second, to validate
      their performance in screening by using Turner syndrome (TS) as a model. DESIGN,
      PATIENTS, AND MAIN OUTCOME MEASURE: Reference values for the height distance from
      TH and growth rate were defined in a total of 14,189 healthy girls aged 0-18 yr
      with 147,469 height measurements. The best formula for TH calculation was TH sd
      score = 0.79 * mid-parental height sd score - 0.15. We also calculated age
      specific limits for the distance from TH and limits for growth rate that were
      freely scalable between age range 0-12 yr. Longitudinal growth data of a cohort
      including 124 TS girls were evaluated with receiver operating characteristic
      analysis against the reference population. RESULTS: The screening accuracy for TS
      was excellent when we combined all three screening parameters. Sensitivity was
      97% and specificity 96% for all TS girls and 100% and 95% for 45,XO TS girls,
      respectively. The detection rate was 68% for all and 76% for 45,XO TS girls with
      99% specificity by the age of 2 yr. CONCLUSION: These new population-based
      screening rules for TS are sensitive and specific, but their use is complex, and
      therefore their efficient use requires computerization.

PMID- 22948764
TI  - Positive effect of daylight exposure on nocturnal urinary melatonin excretion in
      the elderly: a cross-sectional analysis of the HEIJO-KYO study.
AB  - CONTEXT: Melatonin is involved in a variety of diseases, including cancer,
      insomnia, depression, dementia, hypertension, and diabetes; its secretion is
      influenced by environmental light. Although daylight exposure increases nocturnal
      melatonin secretion in a controlled laboratory setting, whether it increases
      nocturnal melatonin secretion in an uncontrolled daily life setting remains
      unclear. OBJECTIVE: We aimed to determine the association between daylight
      exposure in an uncontrolled daily life setting and urinary 6-sulfatoxymelatonin
      excretion. DESIGN AND PARTICIPANTS: A cross-sectional study was conducted in 192
      elderly individuals (mean age, 69.9 yr). MEASURES: We measured ambulatory
      daylight exposure using a wrist light meter in two 48-h sessions; furthermore, we
      measured overnight urinary 6-sulfatoxymelatonin excretion, an index of melatonin
      secretion, on the second night of each session. RESULTS: The median duration of
      daylight exposure of at least 1000 lux was 72 min (interquartile range, 37-124).
      Univariate linear regression analysis showed marginal to significant associations
      between log-transformed urinary 6-sulfatoxymelatonin excretion and age, current
      smoking status, benzodiazepine use, day length, log-transformed duration of
      daylight exposure of at least 1000 lux, and daytime physical activity. In a
      multivariate model, log-transformed duration of daylight exposure of at least
      1000 lux was significantly associated with log-transformed urinary 6
      sulfatoxymelatonin excretion (regression coefficient, 0.101; 95% confidence
      interval, 0.003-0.199; P = 0.043). Furthermore, an increase in the duration of
      daylight exposure of at least 1000 lux from 37 to 124 min (25th to 75th
      percentiles) was associated with a 13.0% increase in urinary 6-sulfatoxymelatonin
      excretion (6.8 to 7.7 MUg). CONCLUSIONS: Daylight exposure in an uncontrolled
      daily life setting is positively associated with urinary 6-sulfatoxymelatonin
      excretion in the elderly.

PMID- 22948765
TI  - Two different corticosteroid-binding globulin variants that lack cortisol-binding
      activity in a greek woman.
AB  - BACKGROUND: Corticosteroid-binding globulin (CBG), encoded by SERPINA6, is the
      principal plasma binding protein for cortisol. Most nonsynonymous single
      nucleotide polymorphisms that alter the production or function of CBG occur
      rarely, and their clinical significance remains obscure. METHODS: Serum and DNA
      were obtained from a Greek woman with low morning cortisol levels and from family
      members. SERPINA6 exons were sequenced, and serum CBG was measured by ELISA and
      cortisol-binding capacity assay. Recombinant CBG variants were produced for
      detailed functional studies. RESULTS: A novel heterozygous c.1282G>C transversion
      in exon 5 of SERPINA6, resulting in a p.Trp393Ser (W371S) substitution, was
      identified in the proband, who was also heterozygous for single-nucleotide
      polymorphisms encoding the CBG Lyon (D367N) and CBG A224S variants. The proband
      had no measurable plasma cortisol-binding activity despite a CBG level of 273 nm
      by ELISA. She inherited CBG W371S from her mother whose plasma cortisol-binding
      capacity was approximately 50% lower than the CBG measurements by ELISA (314 nm).
      The proband's father and four children were heterozygous for CBG D367N; their CBG
      levels by ELISA were normal, but corresponding cortisol-binding capacity
      measurements were 50% lower. Pedigree analysis revealed that W371S segregates
      with A224 and that D367N and W371S segregate separately. Recombinant CBG D367N
      and CBG W371S had no measureable cortisol-binding activity. CONCLUSION: A new CBG
      Athens (W371S) variant that lacks cortisol-binding activity has been identified
      in a carrier of the cortisol-binding deficient CBG Lyon (D367N) variant. Analyses
      of CBG levels in this pedigree illustrate how immunoassays fail to accurately
      reflect cortisol-binding activity.

PMID- 22948766
TI  - Polycystic Ovary-Like Abnormalities (PCO-L) in women with functional hypothalamic
      amenorrhea.
AB  - CONTEXT: In the general population, about 30% of asymptomatic women have
      polycystic ovary-like abnormalities (PCO-L), i.e. polycystic ovarian morphology
      (PCOM) at ultrasound and/or increased anti-Mullerian hormone (AMH) serum level.
      PCOM has also been reported in 30-50% of women with functional hypothalamic
      amenorrhea (FHA). OBJECTIVE: The aim of this study was to verify whether both
      PCOM and excessive AMH level indicate PCO-L in FHA and to elucidate its
      significance. DESIGN: We conducted a retrospective analysis using a database and
      comparison with a control population. SETTING: Subjects received ambulatory care
      in an academic hospital. PATIENTS: Fifty-eight patients with FHA were compared to
      217 control women with nonendocrine infertility and body mass index of less than
      25 kg/m(2). INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We
      measured serum testosterone, androstenedione, FSH, LH, AMH, and ovarian area
      values. The antral follicle count (AFC) was used as a binary variable (i.e.
      negative or positive) because of the evolution of its sensitivity over the time
      of this study. The ability of these variables (except AFC) to detect PCO-L in
      both populations was tested by cluster analysis. RESULTS: One cluster (cluster 2)
      suggesting PCO-L was detected in the control population (n = 52; 24%), whereas
      two such clusters were observed in the FHA population (n = 22 and n = 6; 38 and
      10%; clusters 2 and 3, respectively). Cluster 2 in FHA had similar features of
      PCO-L as cluster 2 in controls, with higher prevalence of positive AFC (70%) and
      PCOM (70%), higher values of ovarian area and higher serum AMH (P < 0.0001 for
      all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in FHA was
      peculiar, with frankly elevated AMH levels. In the whole population (controls +
      FHA), PCO-L was significantly associated with lower FSH values (P < 0.0001).
      CONCLUSION: PCO-L in FHA is a frequent and usually incidental finding of unclear
      significance, as in controls. The association of PCO-L with hypothalamic
      amenorrhea should not lead to a mistaken diagnosis of PCOS.

PMID- 22948767
TI  - Relationship of sympathetic activity to bone microstructure, turnover, and plasma
      osteopontin levels in women.
AB  - CONTEXT: Studies in rodents have demonstrated that sympathetic activity reduces
      bone formation and bone mass; these effects are mediated by the noncollagenous
      matrix protein, osteopontin. OBJECTIVE: The objective of the study was to relate
      sympathetic activity (measured using microneurography at the peroneal nerve) to
      bone microstructure (assessed by high resolution peripheral quantitative computed
      tomography), bone turnover, and plasma osteopontin levels. DESIGN, SETTING, AND
      PATIENTS: Twenty-three women aged 20-72 yr (10 premenopausal and 13
      postmenopausal) were studied in the Clinical Research Unit. RESULTS: Sympathetic
      activity (bursts per 100 heart beats) was 2.4-fold higher in postmenopausal as
      compared with premenopausal women (P < 0.001). In the two groups combined and
      after age adjustment, sympathetic activity was inversely correlated with
      trabecular bone volume fraction (r = -0.55, P < 0.01) and thickness (r = -0.59, P
      < 0.01) and positively correlated with trabecular separation (r = 0.45, P <
      0.05). Sympathetic activity was negatively correlated with serum amino-terminal
      propeptide of type I collagen in postmenopausal women (r = -0.65, P = 0.015),
      with a similar trend in premenopausal women (r = -0.58, P = 0.082). Sympathetic
      activity was also negatively correlated with plasma osteopontin levels (r = 
      0.43, P = 0.045), driven mainly by the correlation in postmenopausal women (r = 
      0.76, P = 0.002). CONCLUSION: These findings represent the first demonstration in
      humans of a relationship between sympathetic activity and bone microstructure and
      circulating levels of amino-terminal propeptide of type I collagen and
      osteopontin. Given the critical role of osteopontin in mediating the effects of
      beta-adrenergic signaling on bone, the inverse association between sympathetic
      activity and plasma osteopontin levels may reflect a negative feedback loop to
      limit the deleterious effects of sympathetic activity on bone metabolism. Based
      on the higher sympathetic activity observed in postmenopausal women, additional
      human studies are needed to define the role of increased sympathetic activity in
      mediating postmenopausal bone loss.

PMID- 22948770
TI  - Iliosacral resections of pelvic malignant tumors and reconstruction with
      nonvascular bilateral fibular autografts.
AB  - BACKGROUND: Iliosacral resection of pelvic malignant tumors and subsequent
      reconstruction have tested the ingenuity of orthopedic oncologists because of the
      difficulty of oncological wide resection and the complex biomechanics of the
      sacroiliac joint render reconstruction challenging. This study compared the
      functional and surgical outcomes of a biological reconstruction technique with
      the lack of reconstruction following iliosacral resection. METHODS: Twenty-six
      consecutive cases with malignant iliac tumors involving the sacrum were
      retrospectively reviewed. These cases underwent iliosacral resection (type I/IV)
      followed by no reconstruction or a biological reconstruction blinded to authors
      between 1997 and 2007. After iliosacral resection, 12 cases underwent
      reconstruction with nonvascular fibular grafts and plate and/or pedicle screw
      rod; the other 14 cases did not undergo reconstruction. RESULTS: The median
      follow-up was 84.42 (range, 32-165) months. The local recurrence rate in the
      reconstruction group was 8.33 % (1/12) with 14.29 % (2/14) in the group without
      reconstruction. The functional score of the biological reconstruction group was
      significantly higher than that of the no-reconstruction group as determined by
      Student's t test. In the biological reconstruction group, bone fusion occurred in
      91 % of cases and fibula hypertrophy was observed in 41.7 %. Complications
      included sciatic nerve palsy, broken screws, intractable pain, nonunion, pelvic
      oblique, and leg-length discrepancy. CONCLUSIONS: After iliosacral resections of
      pelvic malignant tumors, the biologic reconstruction of these defects could
      restore spinopelvic stability and continuity. The double-barrel fibular autograft
      combined with the plate or pedicle screw-rod system is an effective
      reconstruction method for both optimal short- and long-term stability.

PMID- 22948768
TI  - Spreading of X chromosome inactivation via a hierarchy of defined Polycomb
      stations.
AB  - X chromosome inactivation (XCI) achieves dosage balance in mammals by repressing
      one of two X chromosomes in females. During XCI, the long noncoding Xist RNA and
      Polycomb proteins spread along the inactive X (Xi) to initiate chromosome-wide
      silencing. Although inactivation is known to commence at the X-inactivation
      center (Xic), how it propagates remains unknown. Here, we examine allele-specific
      binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during
      XCI and generate a chromosome-wide profile of Xi and Xa (active X) at nucleosome
      resolution. Initially, Polycomb proteins are localized to ~150 strong sites along
      the X and concentrated predominantly within bivalent domains coinciding with CpG
      islands ("canonical sites"). As XCI proceeds, ~4000 noncanonical sites are
      recruited, most of which are intergenic, nonbivalent, and lack CpG islands.
      Polycomb sites are depleted of LINE repeats but enriched for SINEs and simple
      repeats. Noncanonical sites cluster around the ~150 strong sites, and their
      H3K27me3 levels reflect a graded concentration originating from strong sites.
      This suggests that PRC2 and H3K27 methylation spread along a gradient unique to
      XCI. We propose that XCI is governed by a hierarchy of defined Polycomb stations
      that spread H3K27 methylation in cis.

PMID- 22948769
TI  - Copy number variation leads to considerable diversity for B but not A haplotypes
      of the human KIR genes encoding NK cell receptors.
AB  - The KIR complex appears to be evolving rapidly in humans, and more than 50
      different haplotypes have been described, ranging from four to 14 KIR loci.
      Previously it has been suggested that most KIR haplotypes consist of framework
      genes, present in all individuals, which bracket a variable number of other
      genes. We used a new technique to type 793 families from the United Kingdom and
      United States for both the presence/absence of all individual KIR genes as well
      as copy number and found that KIR haplotypes are even more complex. It is
      striking that all KIR loci are subject to copy number variation (CNV), including
      the so-called framework genes, but CNV is much more frequent in KIR B haplotypes
      than KIR A haplotypes. These two basic KIR haplotype groups, A and B, appear to
      be following different evolutionary trajectories. Despite the great diversity,
      there are 11 common haplotypes, derived by reciprocal recombination near KIR2DL4,
      which collectively account for 94% of KIR haplotypes determined in Caucasian
      samples. These haplotypes could be derived from combinations of just three
      centromeic and two telomeric motifs, simplifying disease analysis for these
      haplotypes. The remaining 6% of haplotypes displayed novel examples of expansion
      and contraction of numbers of loci. Conventional KIR typing misses much of this
      additional complexity, with important implications for studying the genetics of
      disease association with KIR that can now be explored by CNV analysis.

PMID- 22948771
TI  - Detection of recurrences during follow-up after liver surgery for colorectal
      metastases: both carcinoembryonic antigen (CEA) and imaging are important.
AB  - BACKGROUND: The follow-up of patients treated for colorectal liver metastases
      (CRLM) is not standardized. The accuracy of an increase in carcinoembryonic
      antigen (CEA) levels for finding recurrences after treatment for CRLM is compared
      in this retrospective cohort study with the accuracy of routine imaging
      modalities of liver and chest. METHODS: Data from all patients in follow-up after
      intentionally curative treatment for CRLM from 1990 to 2010 were analyzed. All
      patients underwent the same follow-up schedule. The way in which recurrences
      became apparent (i.e., CEA increase, routine imaging, or both) was registered.
      The specificity and sensitivity of increases in CEA before finding recurrent
      disease were calculated by receiver operating characteristic (ROC) curves. An
      economic evaluation of the cost per resectable tumor recurrence was performed.
      RESULTS: ROC curves showed that a significant CEA increase was defined as a 25 %
      increase from the previous value. Recurrences were detected in 46 % of the
      procedures through CEA increase concomitant with positive imaging, in 23 %
      through CEA increase without positive findings on routine imaging, and in 31 %
      through positive imaging without an increase in CEA. The resectability of
      recurrences did not differ between triggers. Cost per curable recurrence was
      <euro>2,196 for recurrences found via CEA alone and <euro>6,721 for recurrences
      found with imaging and CEA. CONCLUSIONS: In the follow-up of patients after liver
      surgery for CRLM, a 25 % increase in CEA serum level can accurately detect
      recurrences, but routine imaging is indispensable. In patients with CRLM, we
      advocate both CEA monitoring and imaging in the follow-up after liver surgery.

PMID- 22948772
TI  - Alterations of circulating bone marrow-derived VEGFR-2+ progenitor cells in
      isolated limb perfusion with or without rhTNF-alpha.
AB  - BACKGROUND: Circulating endothelial progenitor cells (cEPCs) as recruited to the
      angiogenic vascular system of malignant tumors have been proposed as a biomarker
      in malignancies. The effect of antitumor chemotherapy on cEPCs is not fully
      understood. We examined the level of cEPCs, vascular endothelial growth factor
      (VEGF), and angiopoietin-2 in the blood of sarcoma and melanoma patients before
      and after isolated limb perfusion (ILP) with or without recombinant human tumor
      necrosis factor-alpha (rhTNF-alpha). METHODS: Twenty-two patients, 11 each with
      soft tissue sarcoma or recurrent melanoma of the limb, were recruited. ILP was
      performed with rhTNF-alpha/melphalan (TNF) or melphalan only (no TNF). Fifteen
      healthy volunteers served as control subjects. Blood was sampled before and up to
      6 weeks after ILP. Peripheral blood mononuclear cells were isolated by density
      gradient centrifugation, and annexin V-negative cells were characterized as cEPCs
      by triple staining for CD133(+), CD34, and VEGFR-2(+). RESULTS: Before treatment,
      cEPC numbers were significantly increased in sarcoma (0.179 +/- 0.190 %) and
      melanoma patients (0.110 +/- 0.073 %) versus healthy controls (0.025 +/- 0.018 %;
      P < 0.01), but did not differ significantly between sarcoma and melanoma
      patients. cEPC decreased significantly after ILP in patients with no TNF compared
      to pretreatment values (P < 0.05) and were significantly lower at 4 h, 48 h, and
      1 week compared to ILP with TNF (P < 0.05). Values 6 weeks after ILP were
      significantly lower than before ILP in both investigated groups (P < 0.01).
      CONCLUSIONS: ILP with TNF results in activation of bone marrow-derived EPCs
      compared to ILP without TNF. Alteration of cEPCs and angiopoietin-2 by rhTNF
      alpha might account for the cytotoxicity and hemorrhagic effects on tumor vessels
      during limb perfusion procedures.

PMID- 22948774
TI  - Recurrent lymphoma in the thyroid gland detected by fluorine-18
      fluorodeoxyglucose PET/CT.

PMID- 22948773
TI  - Erectile dysfunction as a cardiovascular risk factor in patients with diabetes.
AB  - Erectile dysfunction (ED) is a highly prevalent disorder among patients with
      diabetes mellitus (DM). In most cases, ED is considered a vascular disease and
      its development is significantly related to the exposure to CVD risk factors. In
      this context, ED and coronary artery disease (CAD) have been proposed as
      different manifestations of the same systemic disease; in nondiabetic patients,
      ED has progressively emerged as an important sentinel marker of the subsequent
      onset of CVD events. The aim of this review was to evaluate the association
      between ED and CAD in diabetic patients and to evaluate the role of ED as an
      independent CVD risk factor in these patients. Three large prospective studies
      confirmed that ED is a powerful predictor of CAD and cardiac mortality in
      patients with DM. Overall, diabetic patients with ED had roughly 1.4-fold higher
      risk of CAD as compared with those without ED. Interestingly, in diabetic
      patients, CAD is often silent and CAD screening according to the current
      guidelines can miss up to 40 % patients with occult myocardial perfusion
      abnormalities. Indeed, patients with ED have higher risk of silent myocardial
      ischemia compared to those without ED, and when ED is added to the risk factors,
      it can even improve the sensitivity of screening for asymptomatic CAD. Therefore,
      ED should be considered an independent CVD risk factor, and it could improve the
      identification of diabetic patients suitable for screening, leading to an early
      detection of CAD, and thus potentially enhancing the therapeutic effectiveness.

PMID- 22948775
TI  - Resistance training decreases serum inflammatory markers in diabetic rats.
AB  - Inflammation plays an important role in the genesis and progression of diabetes.
      The purpose of this study was to investigate the effect of resistance training on
      serum levels of some inflammatory markers associated with diabetes mellitus.
      Twenty-four male Wistar rats (290 +/- 19 g) were randomly divided into three
      groups: non-diabetic control (non-DC), diabetic control (DC), and diabetic
      trained (DT). Animals in DT group were subjected to a resistance training program
      with the use of a ladder (3 days/week, for 4 weeks). Body weight, serum high
      sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis
      factor (TNF)-alpha, fasting glucose, and insulin were measured. Four weeks of
      resistance training decreased serum levels of TNF-alpha, hs-CRP, and IL-6 in
      diabetic rats when compared with DC animals. We conclude that resistance training
      with appropriate intensity, duration, and recovery between exercise bouts has
      marked anti-inflammatory effects on diabetic rats. This may be an efficient
      strategy to protect against some diabetic complications.

PMID- 22948776
TI  - Aberrant SERCA3 expression is closely linked to pathogenesis, invasion,
      metastasis, and prognosis of gastric carcinomas.
AB  - Sarco (endo)plasmic reticulum Ca(2+)-ATPase (SERCAs) 3 is involved in calcium
      mobilization from endoplasmic reticulum into cytosol and closely links to
      metabolism, neuronal plasticity, gene transcription, cell growth,
      differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the
      role of SERCA3 in gastric carcinogenesis and subsequent progression, its
      expression was examined by immunohistochemistry and in situ hybridization (ISH)
      on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic
      mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric
      carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase
      chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was
      distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC
      803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The
      carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time
      PCR and ISH (P > 0.05). Immunohistochemically, SERCA3 expression was decreased
      from gastric NNM, primary to metastatic carcinoma (P > 0.05). SERCA3 expression
      was negatively related to depth of invasion, distant metastasis, and tumor node
      metastasis (TNM) staging (P > 0.05), but not to age, sex, lymphatic or venous
      invasion, or lymph node metastasis (P > 0.05). Kaplan-Meier analysis indicated
      that SERCA3 expression was positively associated with favorable prognosis of the
      patients with gastric carcinoma (P > 0.05). Cox's proportional hazard model
      indicated that venous invasion, distant metastasis and TNM staging (P > 0.05)
      were independent prognostic factors for gastric carcinomas. It was suggested that
      downregulated SERCA3 expression is closely linked to pathogenesis, invasion,
      metastasis, and prognosis of gastric carcinomas. It might be employed to indicate
      the pathobiological behaviors and prognosis of gastric carcinomas.

PMID- 22948777
TI  - The kallikrein-related peptidase 13 (KLK13) gene is substantially up-regulated
      after exposure of gastric cancer cells to antineoplastic agents.
AB  - Gastric cancer constitutes one of the most common neoplasms globally. Kallikrein
      related peptidases have attracted interest as potential tumor markers and future
      targets for novel cancer therapeutics. We have recently reported KLK13 clinical
      importance as a favorable prognostic biomarker for gastric cancer patients'
      survival. By aiming to explore how the molecular profile of KLK13 is modified in
      stomach cancer cells treated with antineoplastic drugs, we examined, for the
      first time, the mRNA alterations of this gene following gastric cancer cells'
      exposure to the prominent chemotherapeutic substances epirubicin, oxaliplatin, or
      methotrexate. The antiproliferative effects of these agents, on AGS cells'
      growth, were determined by the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and trypan blue assays. Total RNA, isolated from the
      harvested cells, was reverse-transcribed to cDNA. KLK13 levels were quantified
      via real-time PCR using the SYBR Green chemistry. The relative changes of KLK13
      expression were calculated with the comparative C (t) (2(-ddCt)) method. Distinct
      KLK13 profiles resulted from AGS cells' incubation with epirubicin or
      methotrexate for 24, 36, and 48 h. KLK13 expression increased in a time-dependent
      manner up to 5.70 times (for epirubicin) or 5.76 times (for methotrexate) at 48 h
      compared with the corresponding untreated cells. According to our results, KLK13
      expression is implicated in the molecular pathways that are triggered after
      administration of anticancer agents on gastric cancer cells. Moreover, our data
      support the possibility that KLK13 may be exploited as a future molecular
      predictor of gastric cancer cells' response to chemotherapy.

PMID- 22948778
TI  - CYP1A1 Ile462Val polymorphism and cervical cancer: evidence from a meta-analysis.
AB  - Many publications have evaluated the correlation between Cytochrome P450 1A1
      (CYP1A1) Ile462Val polymorphism and cervical cancer risk, but the results remain
      inconclusive. To provide a more robust estimate of this effect, a meta-analysis
      was carried out. We systematically searched PubMed, Embase and CBM databases for
      studies published before May 2012. The association between CYP1A1 Ile462Val
      polymorphism and cervical cancer risk was assessed by calculating pooled odds
      ratios (OR) with its 95 % confidence intervals (95 % CI). On the basis of our
      inclusion criteria, ten studies with a total of 2,423 individuals were included
      in the meta-analysis. Overall, CYP1A1 Ile462Val polymorphism was associated with
      increased risk of cervical cancer (Val versus Ile, OR = 1.43; 95 % CI, 1.03-1.97;
      ValVal versus IleIle, OR = 2.43; 95 % CI, 1.19-4.95; ValVal+ValIle versus IleIle,
      OR = 1.59; 95 % CI, 1.00-2.53). Ethnic subgroup analyses showed a significant
      association was found in Caucasians (Val versus Ile, OR = 2.03; 95 % CI, 1.17
      3.51; ValVal versus IleIle, OR = 2.74; 95 % CI, 1.30-5.75; ValVal+ValIle versus
      IleIle, OR = 2.50; 95 % CI, 1.33-4.70), but not in Asians. In conclusion, this
      meta-analysis suggests that CYP1A1 Ile462Val polymorphism plays an important role
      in susceptibility to cervical cancer. Further studies with large sample size and
      careful design need performing to identify this association more comprehensively.

PMID- 22948779
TI  - A clinical study on regional lymphatic chemotherapy using an activated carbon
      nanoparticle-epirubicin in patients with breast cancer.
AB  - The purpose of this study was to understand the short-term therapeutic effects of
      an activated carbon nanoparticle-epirubicin suspension for regional lymphatic
      chemotherapy in patients with breast cancer. One hundred and twenty patients with
      stage I, II, or III primary breast cancer were randomly divided into three
      groups: the lymphatic chemotherapy group using the activated carbon nanoparticle
      epirubicin suspension, the epirubicin control group, and the activated carbon
      control group. Each group of 40 patients was further divided into two subgroups
      with the drug injected either 24 or 48 h before surgery. The terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL) assay was used to determine cancer cell apoptotic indices in
      metastatic lymph nodes. The epirubicin concentration in the black-stained lymph
      nodes in the lymphatic chemotherapy treatment group was 4,144.64 +/- 2,426.44
      ng/g, which is significantly higher than in the epirubicin control group (335.87
      +/- 212.82 ng/g, P < 0.001). The plasma epirubicin concentrations at 0.5, 1.5,
      and 24 h postinjection in the regional lymphatic chemotherapy treatment group
      were significantly lower than in the epirubicin control group (P < 0.001).
      Tolerable mild pain was observed at the injection area after administration of
      the epirubicin-activated carbon nanoparticle suspension. No regional necrosis or
      adverse effects were found. The TUNEL assay demonstrated that there was no
      significant difference in the apoptotic indices in the metastatic lymph nodes
      from the three groups. Performing lymphatic chemotherapy by regionally injecting
      the epirubicin-activated carbon nanoparticle suspension could significantly
      enhance the drug concentration in the stained lymph nodes and lower the plasma
      drug concentration. The epirubicin-activated carbon nanoparticle suspension has
      the ability to release the drug slowly in the lymph nodes and, as a result, can
      prolong the chemotherapeutic effects.

PMID- 22948780
TI  - Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer.
AB  - Results from studies on efficacy of carcinoembryonic antigen (CEA), carbohydrate
      antigen 15.3 (CA 15.3) and thymidine kinase (TK1) as diagnostic and prognostic
      tools for primary breast cancer (BC) have presented conflicting results, and
      usefulness of these markers for clinical use in BC remains unclear. The aim of
      this study is to evaluate potential of concentration of the sera CEA, CA15.3 and
      TK1 peptides' use as markers in the diagnosis and prognosis of breast lesions of
      Libyan patients. Serum tumour markers were studied in 20 healthy subjects, 30
      patient with benign lesion diseases and 50 patients with histologically confirmed
      BC diagnosed at the National Cancer Institute (NCI), Misurata, Libya during the
      period 2005-2009. The concentrations of the BC patients' cutoff points used for
      diagnostic and prognostic sensitivity were 8.82 ng/ml, 35.57 U/ml and 32.57
      U/mg/protein for CEA, CA15.3 and TK1, respectively. Increased CEA (>8.82 ng/ml),
      CA 15.3 (>35.57 U/ml) and TK1 (>32.57 U/mg/protein) concentrations were found in
      62 %, 70 % and 78 % of the BC patients, respectively. For all three tumour
      markers, increased concentrations correlated increased tumour size and nodal
      involvement. Significantly higher serum TK1 levels were found in patients with
      advanced disease (p < 0.0001) and TK1 levels also correlated with disease
      specific survival (DSS, p < 0.07). The combined data set of the three markers'
      data from three markers increased the diagnostic sensitivity to 90 %. The serum
      marker analysis for CEA, CA 15.3, and S-TK1 concentrations is shown to be a
      useful tool for identification of malignant cases in our BC population and for
      the prognostic evaluation of patients with primary BC. Increased concentrations
      of the markers were also observed to be higher in patients with advanced tumours
      and indicative of the development of distant metastasis.

PMID- 22948781
TI  - The effect of lysyl oxidase polymorphism on susceptibility and prognosis of
      nonsmall cell lung cancer.
AB  - Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important
      roles in development and homeostasis of the lungs. The aim of this study was to
      investigate whether polymorphisms in the LOX gene were associated with
      susceptibility to nonsmall cell lung cancer (NSCLC). We sequenced the promoter
      region of LOX gene and tested the previously reported polymorphism 473 G/A in the
      Han Chinese population. A novel polymorphism, -22 G/C, was identified in the
      promoter region of LOX. However, it did not show any correlation with NSCLC.
      Frequencies of the 473AA genotype and 473A allele were significantly higher in
      the NSCLC cases than in control group (p = 0.004 and p = 0.006, respectively).
      Further, our results showed that survival time of NSCLC patients with 473AA
      genotype was significantly shorter compared to the cases carrying 473 G allele
      (20.0 months vs. 28.0 months, p = 0.011). These data indicate that LOX 473 G/A
      polymorphism is associated with increased risk of NSCLC and can be a prognostic
      predictor for this disease.

PMID- 22948782
TI  - Scanning photocurrent microscopy of lateral organic bulk heterojunctions.
AB  - Scanning confocal photocurrent microscopy has been used to characterize carrier
      collection efficiency in lateral bulk heterojunction devices. By analyzing the
      photocurrent mappings within these devices, the lateral extents of the space
      charge regions has been measured and reported. Modulation via white light bias or
      increased voltage bias is also shown to increase the size of the space charge
      regions.

PMID- 22948783
TI  - Variation in the effects of three different breakfast meals on subjective satiety
      and subsequent intake of energy at lunch and evening meal.
AB  - PURPOSE: To determine the relative impact of three iso-caloric breakfast meals,
      of variable composition, on satiety, hunger and subsequent intake of energy.
      METHODS: In a three-way, crossover design, 30 healthy men (age of 21.7 +/- 1.2
      years; BMI, 23.1 +/- 2.7 kg/m2) were randomised to one of three test breakfasts,
      on three separate occasions, separated by 1 week. The breakfasts consisted of
      eggs on toast, cereal (cornflakes) with milk and toast, or a croissant and orange
      juice. Subjective ratings of satiety, hunger, fullness and desire to eat were
      recorded at 30-min intervals by electronic visual analogue scales (VAS). Energy
      intake was assessed by weighed food intake at an ad libitum lunch and evening
      meal. RESULTS: Participants showed increased satiety, less hunger and a lower
      desire to eat after the breakfast containing eggs relative to the cereal (p <
      0.02), and croissant-based meals (p < 0.0001). The egg breakfast was also
      accompanied by a significantly lower intake of energy relative to the croissant-
      and cereal-based breakfasts at the buffet lunch and evening meal, respectively,
      1,284 +/- 464 (egg) versus 1,442 +/- 426 kcal (croissant), p = 0.03, 1,407 +/-
      379 (cereal) at lunch and 1,899 +/- 729 (egg) versus 2,214 +/- 620 kcal (cereal),
      p = 0.02, 2,047 +/- 712 (croissant) at evening meal. The breakfast meal with the
      greatest effect on satiety and subsequent intake of energy was distinct in having
      the highest protein and lowest carbohydrate content relative to the other two
      breakfasts. CONCLUSION: These findings provide evidence to support the importance
      of food choice at breakfast as a means of increasing satiety in the morning and
      reducing energy intake at lunch.

PMID- 22948784
TI  - Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible
      factor-1alpha in human colon carcinoma: impact of ESM-1 on prognosis and its
      correlation with clinicopathological features.
AB  - Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1) is
      a potential serum marker for colorectal cancer (CRC), the aim of this study was
      to clarify the clinicopathological significance of ESM-1 expression in CRC, and
      to explore the correlation between ESM-1 and HIF-1alpha in the tumorigenesis of
      CRC related to hypoxic conditions. ESM-1 mRNA expression was examined in CRC and
      corresponding normal mucosal tissues by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and real-time RT-PCR. This experiment confirmed that ESM-1
      levels were high in CRC. We screened the tissue samples of 143 CRC patients. By
      immunohistochemistry, we determined that the ESM-1 immunoreactivity was
      significantly correlated with the tumor size, depth of invasion, nodal status,
      distant metastasis and Dukes' stage, and was an independent prognostic factor for
      disease recurrence and worse survival outcome (P=0.001). The modulation of ESM-1
      under hypoxia was investigated, and it was confirmed that ESM-1 expression was
      induced by HIF1-alpha and significantly attenuated by small interfering RNA
      (siRNA) targeting HIF-1alpha in CRC cells. These results showed that ESM-1 is
      significantly overexpressed, which is regulated by HIF-1alpha in CRC patients,
      and can be used as a potential biomarker and a therapeutic target for CRC.

PMID- 22948785
TI  - Cuticular hydrocarbons of the South American fruit fly Anastrepha fraterculus:
      variability with sex and age.
AB  - Insect cuticular hydrocarbons are usually species-specific mixtures and may serve
      for species and gender recognition. They are, therefore, widely used in the
      chemotaxonomy and zoogeography of various insect taxa. In order to provide a
      basic study for further comparative analyses of cuticular hydrocarbon (CHC)
      profiles of cryptic species hidden within the South American fruit fly Anastrepha
      fraterculus complex (Diptera: Tephritidae), we analyzed the composition of the
      CHCs and their production with respect to age and sex in a laboratory population
      from Tucuman, Argentina. Several techniques of gas chromatography with mass
      spectrometric detection have been used in order to develop a suitable method for
      CHC identification, i.e., GC-MS in EI mode, GC-MS in CI mode, and GC*GC/TOFMS.
      Our analyses revealed a complex profile of aliphatic hydrocarbons in both males
      and females, consisting predominantly of n-alkanes, methyl-branched alkanes, as
      well as of alkenes and alkadienes. In young individuals (up to about 5 days after
      emergence), the CHC profiles were similar in males and females. However, in older
      flies, these profiles diverged and became clearly sex-specific. The temporal
      dynamics of the CHC patterns in both sexes were evaluated using multivariate
      exploratory techniques.

PMID- 22948786
TI  - The teamwork in assertive community treatment (TACT) scale: development and
      validation.
AB  - OBJECTIVE: Team design is meticulously specified for assertive community
      treatment (ACT) teams, yet performance can vary across ACT teams, even those with
      high fidelity. By developing and validating the Teamwork in Assertive Community
      Treatment (TACT) scale, investigators examined the role of team processes in ACT
      performance. METHODS: The TACT scale measuring ACT teamwork was developed from a
      conceptual model grounded in organizational research and adapted for the ACT and
      mental health context. TACT subscales were constructed after exploratory and
      confirmatory factor analyses. The reliability, discriminant validity, predictive
      validity, temporal stability, internal consistency, and within-team agreement
      were established with surveys from approximately 300 members of 26 Minnesota ACT
      teams who completed the questionnaire three times, at six-month intervals.
      RESULTS: Nine TACT subscales emerged from the analyses: exploration, exploitation
      of new and existing knowledge, psychological safety, goal agreement, conflict,
      constructive controversy, information accessibility, encounter preparedness, and
      consumer-centered care. These nine subscales demonstrated fit and temporal
      stability (confirmatory factor analysis), high internal consistency (Cronbach's
      alpha), and within-team agreement and between-team differences (rwg and
      intraclass correlations). Correlational analyses of the subscales revealed that
      they measure related yet distinctive aspects of ACT team processes, and
      regression analyses demonstrated predictive validity (encounter preparedness is
      related to staff outcomes). CONCLUSIONS: The TACT scale demonstrated high
      reliability and validity and can be included in research and evaluation of
      teamwork in ACT and mental health teams.

PMID- 22948787
TI  - Future trials of endovascular mechanical recanalisation therapy in acute ischemic
      stroke patients: a position paper endorsed by ESMINT and ESNR : part I: Current
      situation and major research questions.
AB  - A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by
      fully deployed closed-cell self-expanding stents (stent-triever). Multiple case
      series and the first randomised controlled trials (RCTs) have now been published.
      More studies are under way involving large numbers of patients, which in turn has
      resulted in less strict "pragmatic" study protocols. Problems with current trials
      include a lack of standardisation in the conduct of the recanalisation procedure,
      the definition of primary endpoints such as the grade of arterial recanalisation
      and tissue reperfusion, and the post-surgical care provided. In Part 1 of this
      two part series, we outline the current situation and the major research
      questions.

PMID- 22948788
TI  - Future trials of endovascular mechanical recanalisation therapy in acute ischemic
      stroke patients - a position paper endorsed by ESMINT and ESNR : part II:
      methodology of future trials.
AB  - Based on current data and experience, the joint working group of the European
      Society of Minimally Invasive Neurological Therapy (ESMINT) and the European
      Society of Neuroradiology (ESNR) make suggestions on trial design and conduct
      aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We
      anticipate that this roadmap will facilitate the setting up and conduct of
      successful trials in close collaboration with our neighbouring disciplines.

PMID- 22948789
TI  - Reconsidering the effects of poverty and social support on health: a 5-year
      longitudinal test of the stress-buffering hypothesis.
AB  - Prior research in the general population has found that social support can buffer
      the adverse effects of stressors on health. However, both stressors and social
      support may be qualitatively different for those living in urban poverty. We
      examined the effects of social support and poverty-specific stressors on self
      rated health. We used data from the Welfare Client Longitudinal Survey (WCLS), a
      5-year longitudinal study of 718 public aid recipients. We measured received
      social support and "net social support," defined as the difference between
      support received and that given to others. We used restricted cubic splines to
      model the stress-buffering effects of social support on self-rated health as a
      function of stressful life events and neighborhood disorder. Increased exposure
      to stressors was associated with poorer self-rated health. Evidence of stress
      buffering was confined to those with the heaviest exposure to stressors, and its
      effects decreased across increasing levels of social support. Analyses using net
      social support had generally more modest effects than those using received social
      support. Social support does not buffer the effects of stressors on health
      uniformly for individuals living in conditions of urban poverty. Researchers and
      policymakers should be cautious in overestimating the beneficial effects that
      social support may have on health for marginalized populations.

PMID- 22948790
TI  - Target population involvement in urban ciclovias: a preliminary evaluation of St.
      Louis open streets.
AB  - Ciclovias are active street events when roads are open to walkers, cyclists, and
      families and closed to automobiles. Over 70 cities in the USA have implemented
      ciclovias to promote physical activity. The authors evaluated four events during
      2010 to determine what activities participants perform and who is attending. For
      two ciclovia events in St. Louis, Missouri, observation reports of activities,
      gender, and age of 1,452 participants were collected, and 82 adults were
      interviewed via direct approach. The survey covered six domains: physical
      activity, travel to event, sense of community, marketing, economic impact, and
      demographics. Each event occurred within the city, along multiple streets.
      Domains were selected from Ciclovia Recreativa developed by Ciclovia Bogota, Pan
      American Health Organization, and CDC. Additional questions addressed city
      specific goals and matched similar evaluations in other cities. Over 50 % of
      participants met CDC-defined weekly minute thresholds for physical activity.
      Participants, primarily (>80 %) middle class, college educated, and white, were
      not representative of the majority minority city population, which has high rates
      of poverty, and low percentage of college graduates. Cities must work with
      residents to increase low-income minority population participation in ciclovia
      based physical activity. 

PMID- 22948791
TI  - Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate
      cyclization: concise synthesis of 2,6-cis-substituted tetrahydropyran
      derivatives.
AB  - Herein, we describe the concise synthesis of 2,6-cis-substituted tetrahydropyran
      derivatives based on a domino olefin cross-metathesis/intramolecular oxa
      conjugate cyclization (CM/IOCC) reaction. We have found that the domino CM/IOCC
      of delta-hydroxy olefins with alpha,beta-unsaturated carbonyl compounds (e.g.,
      trans-crotonaldehyde or N-acryloyl-2,5-dimethylpyrrole) could be efficiently
      achieved in the presence of the second-generation Hoveyda-Grubbs catalyst under
      elevated temperature conditions, directly affording 2,6-cis-substituted
      tetrahydropyrans in excellent yields with synthetically useful
      diastereoselectivity ("auto-tandem catalysis"). In addition, we have found that
      the domino CM/IOCC of delta-hydroxy olefins with alpha,beta-unsaturated carbonyl
      compounds could be achieved simply by performing CM in the presence of a Bronsted
      acid in CH(2)Cl(2) at 25-35  degrees C, which delivered 2,6-cis-substituted
      tetrahydropyrans in good yields with excellent diastereoselectivity ("orthogonal
      tandem catalysis"). To understand the mechanism of auto-tandem catalysis in the
      domino CM/IOCC reaction, we have investigated the role of ruthenium hydride
      complexes in the IOCC of a zeta-hydroxy alpha,beta-unsaturated ketone as a model
      case.

PMID- 22948792
TI  - The cyclooxygenase and nitric oxide synthesis/pathways mediate the inhibitory
      serotonergic response to the pressor effect elicited by sympathetic stimulation
      in long-term diabetic pithed rats.
AB  - We investigated the mechanisms involved in the 5-hydroxytriptaminergic inhibitory
      action on the pressor responses elicited by sympathostimulation in long-term
      diabetic pithed rats. Diabetes was induced in rats by alloxan administration.
      Eight weeks later, the animals were anaesthetized and pithed. The action and
      mechanisms of 5-HT were analysed based on the pressor responses induced by
      sympathostimulation. In 8-week-diabetic animals, 5-HT (20 ug/kg/min) inhibits the
      pressor effect of sympathostimulation which is reproduced by two selective 5
      HT(1A) and 5-HT(2) receptor agonists: 8-hydroxydipropylaminotetralin hydrobromide
      (8-OH-DPAT, 5 ug/kg/min) and alpha-methyl-5-HT (5 ug/kg/min). A bolus injection
      of 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 10 ug/kg), or L-arginine
      HCl, N(omega)-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg), an
      inhibitor of NO production, prior to the infusion of 8-OH-DPAT (5 ug/kg/min)
      reversed the inhibitory effect of 8-OH-DPAT. The inhibitory effect of infusion of
      alpha-methyl 5-HT (5 ug/kg/min) was abolished in the presence of indomethacin (2
      mg/kg), a non-selective cyclooxygenase (COX) inhibitor, or FR 122047 (1.5 mg/kg)
      or nimesulide (1.5 mg/kg), two selective COX-1 and COX-2 inhibitors,
      respectively, in long-term-diabetic pithed rats. Our results indicate that 5-HT
      inhibition of the pressor responses induced by electrical stimulation is mediated
      both by the NO and COX pathways in long-term-diabetic rats.

PMID- 22948793
TI  - Association between diastolic dysfunction by color tissue Doppler imaging and
      vascular calcification on plain radiographs in dialysis patients.
AB  - BACKGROUND/AIM: Diastolic dysfunction is frequently associated with left
      ventricular hypertrophy, which is indicative of future cardiovascular events.
      Vascular calcification (VC) is known to be associated with coronary artery
      disease in dialysis patients. The present study was to determine the
      interrelationship between LV diastolic dysfunction by tissue Doppler imaging and
      VC on plain radiographs in dialysis patients. METHODS: Fifty-six dialysis
      patients were recruited and VC scores were evaluated by plain radiographic film.
      The ratio of early diastolic transmitral inflow velocity (E) to early diastolic
      mitral annular velocity (E') was measured by tissue Doppler imaging. We defined
      diastolic dysfunction as an E/E' ratio >15 on tissue Doppler imaging. RESULTS:
      Patients with diastolic dysfunction showed a higher percentage of coronary artery
      disease history, abdominal aortic calcification (AAC) scores >=5, high LV mass
      index, and high left atrium volume compared to patients without diastolic
      dysfunction. The E/E' ratio was significantly higher in patients with significant
      VC, VC scores of the pelvis and hands >=3, and AAC scores >=5 on plain
      radiographs. AAC scores >=5 were considered an independent predictor of diastolic
      dysfunction. CONCLUSION: VC on plain radiographs is associated with the E/E'
      ratio and AAC scores >=5 are important clues for LV diastolic dysfunction in
      dialysis patients.

PMID- 22948794
TI  - Extranodal T-cell/histiocyte-rich large B-cell lymphoma presenting primarily on
      the skin.

PMID- 22948795
TI  - Effect of crocin on the insulin resistance and lipid profile of streptozotocin
      induced diabetic rats.
AB  - Crocin is the only water soluble carotenoid in nature, and it has a known
      powerful antioxidant activity. The aim of this work was to investigate the
      hypoglycemic and hypolipidemic effects of crocin in streptozotocin (STZ)-induced
      type 2 diabetic rats. Neonatal male Wistar rats (2-5 days old) were randomly
      divided into five groups. Three groups were intraperitoneally injected with STZ
      (90 mg/kg body weight). Among them, two groups were treated with intraperitoneal
      injection of crocin (50 or 100 mg/kg), and the third group was treated with
      vehicle only. Two control groups were also considered, and one of them was
      treated with crocin. After 5 months, their blood and urine samples were
      collected, and the animals were sacrified. The results indicate a significant
      lower body weight (P < 0.001) and abnormal parameters in the diabetic rats
      compared with the normal group. An administration of both doses of crocin
      significantly decreased the levels of serum glucose, advanced glycation end
      products, triglyceride, total cholesterol, and low-density lipoprotein and
      increased the high-density lipoprotein in the diabetic rats. The treatments were
      also effective in decreasing HbA1c and microalbuminuria, as well as homeostatic
      model assessment for insulin resistance as a measure of insulin resistance in the
      diabetic rats.

PMID- 22948796
TI  - Efficient inhibition of porcine reproductive and respiratory syndrome virus
      replication by artificial microRNAs targeting the untranslated regions.
AB  - A robust artificial microRNA (amiRNA) strategy against porcine reproductive and
      respiratory syndrome virus (PRRSV) was developed by targeting the untranslated
      regions (UTRs). Six candidate amiRNAs targeting the 5' or 3' UTR were used for
      vector construction, and four effective amiRNAs were selected for further study
      using a vector transfection/virus infection assay. In cell cultures stably
      transfected with the four amiRNA vectors, expression of the sequence-specific
      amiRNAs was confirmed using poly(A)-tailed RT-PCR. After infection with three
      different PRRSV strains, the viral RNA genome and/or transcript were inhibited by
      ~90 % (semi-quantitative RT-PCR), and the viral titers were decreased by more
      than six log CCID(50) (viral titration assay) before day 3 postinfection. The
      potent anti-PRRSV effects lasted for at least 5 days. Sequence analysis showed
      that the amiRNA antiviral activities were not compromised by the presence of one
      or two mismatches in their binding targets. This work constitutes a step towards
      developing a more effective RNAi strategy against PRRSV.

PMID- 22948798
TI  - From linking of metal-oxide building blocks in a dynamic library to giant
      clusters with unique properties and towards adaptive chemistry.
AB  - Following Nature's lessons, today chemists can cross the boundary of the small
      molecule world to construct multifunctional and highly complex molecular nano
      objects up to protein size and even cell-like nanosystems showing responsive
      sensing. Impressive examples emerge from studies of the solutions of some
      oxoanions of the early transition metals especially under reducing conditions
      which enable the controlled linking of metal-oxide building blocks. The latter
      are available from constitutional dynamic libraries, thus providing the option to
      generate multifunctional unique nanoscale molecular systems with exquisite
      architectures, which even opens the way towards adaptive and evolutive
      (Darwinian) chemistry. The present review presents the first comprehensive report
      of current knowledge (including synthesis aspects not discussed before) regarding
      the related giant metal-oxide clusters mainly of the type {Mo(57)M'(6)} (M' =
      Fe(III), V(IV)) (torus structure), {M(72)M'(30)} (M = Mo, M' = V(IV), Cr(III),
      Fe(III), Mo(V)), {M(72)Mo(60)} (M = Mo, W) (Keplerates), {Mo(154)}, {Mo(176)},
      {Mo(248)} ("big wheels"), and {Mo(368)} ("blue lemon") - all having the important
      transferable pentagonal {(M)M(5)} groups in common. These discoveries expanded
      the frontiers of inorganic chemistry to the mesoscopic world, while there is
      probably no collection of discrete inorganic compounds which offers such a
      versatile chemistry and the option to study new phenomena of interdisciplinary
      interest. The variety of different properties of the sphere- and wheel-type metal
      oxide-based clusters can directly be related to their unique architectures: The
      spherical Keplerate-type capsules having 20 crown-ether-type pores and tunable
      internal functionalities allow the investigation of confined matter as well as
      that of sphere-surface-supramolecular and encapsulation chemistry - including
      related new aspects of the biologically important hydrophobic effects - but also
      of nanoscale ion transport and separation. The wheel-type molybdenum-oxide
      clusters exhibiting complex landscapes do not only have well-defined reaction
      sites but also show unprecedented adaptability regarding the integration of
      various kinds of matter. Applications in different fields, e.g. in materials
      science and catalysis including those in small spaces, investigated by several
      groups, are discussed while possible directions for future work are outlined.

PMID- 22948797
TI  - The use of Permacol(r) injections for the treatment of faecal incontinence.
AB  - The aim of this study is to assess the safety and efficacy of Permacol((r))
      implant for the treatment of idiopathic faecal incontinence using a novel
      injection technique. Patients with idiopathic passive faecal incontinence were
      selected for trans-submucosal injection of Permacol((r)) after assessment by
      anorectal physiology and endoanal ultrasonography. Clinical assessment and St.
      Mark's Incontinence Score were used to evaluate efficacy before and at two time
      points (1 and 2 years) after treatment. Rockwood Score were also used to
      determine quality of life before and after treatment. The Friedman and Chi-square
      tests were used to compare continuous and categorical data, respectively. A p
      value of <0.05 was deemed significant. Thirty-eight patients (24 female), median
      age 66 years, were recruited. At maximum clinical follow-up (median of 9 months),
      response to Permacol((r)) injections was categorised as excellent, good, fair and
      poor in 12, 5, 4 and 17 patients, respectively. St. Mark's Score improved in 72
      and 63 % of patients at 1 and 2 years, respectively. However, a smaller
      proportion of patients (39 and 27 %, respectively) achieved a 50 %, or more,
      improvement in Mark's Score. All four domains of Rockwood Quality of Life Score
      improved on first and second year follow-up, however, only two domains, coping
      and embarrassment, were statistically significant. Permacol((r)) injection
      improved symptoms by >50 % in 39 and 27 % of patients on short and medium-term
      follow-ups, respectively. The trans-submucosal technique for injection of
      Permacol((r)) in this study was safe with no significant adverse outcomes.

PMID- 22948799
TI  - Prodrug of green tea epigallocatechin-3-gallate (Pro-EGCG) as a potent anti
      angiogenesis agent for endometriosis in mice.
AB  - Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and
      development of an experimental endometriosis model in mice, but it suffers from
      poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized
      to enhance the stability and bioavailability of EGCG in vivo. In this study, the
      potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in
      mice was investigated. Homologous endometrium was subcutaneously transplanted
      into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4
      weeks. The growth of the endometrial implants were monitored by IVIS((r)) non
      invasive in vivo imaging during the interventions. Angiogenesis of the
      endometriotic lesions was determined by Cellvizio((r)) in vivo imaging and
      SCANCO((r)) Microfil microtomography. The bioavailability, anti-oxidation and
      anti-angiogenesis capacities of the treatments were measured in plasma and
      lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle
      layers were collected for histological, microvessel and apoptosis examinations.
      The result showed that EGCG and pro-EGCG significantly decreased the growth of
      endometrial implants from the 2nd week to the 4th week of intervention. EGCG and
      pro-EGCG significantly reduced the lesion size and weight, inhibited functional
      and structural microvessels in the lesions, and enhanced lesion apoptosis at the
      end of interventions. The inhibition by pro-EGCG in all the angiogenesis
      parameters was significantly greater than that by EGCG, and pro-EGCG also had
      better bioavailability and greater anti-oxidation and anti-angiogenesis
      capacities than EGCG. Ovarian follicles and uterine endometrial glands were not
      affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In
      conclusion, pro-EGCG significantly inhibited the development, growth and
      angiogenesis of experimental endometriosis in mice with high efficacy,
      bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could
      be a potent anti-angiogenesis agent for endometriosis.

PMID- 22948800
TI  - Diet linked to cancer. Editor's note.

PMID- 22948801
TI  - Diet and breast cancer: understanding risks and benefits.
AB  - BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in
      the United States. Extensive research has been completed to evaluate the
      relationship between dietary factors and breast cancer risk and survival after
      breast cancer; however, a summary report with clinical inference is needed.
      Materials and METHODS: This review summarizes the current epidemiological and
      clinical trial evidence relating diet to breast cancer incidence, recurrence,
      survival, and mortality. The review includes emerging epidemiological studies
      that assess risk within breast cancer subtypes as well as a summary of previous
      and ongoing dietary intervention trials designed to modify breast cancer risk.
      RESULTS: The available literature suggests that both low-fat and high-fiber diets
      may be weakly protective against breast cancer, whereas total energy intake and
      alcohol appear to be positively associated. Fiber may be weakly protective
      possibly through modulation of estrogen, whereas fruit and vegetable intake is
      not clearly associated with risk. Obesity is a risk factor for postmenopausal
      disease, and adult weight gain should be avoided to reduce risk. In survivors,
      diet has the greatest potential influence on overall mortality rather than breast
      cancer-specific events. CONCLUSION: Diet is modestly associated with breast
      cancer risk; associations appear more pronounced for postmenopausal disease, and
      healthy choices after diagnosis and treatment likely support longevity more so
      than reduced risk for recurrent disease.

PMID- 22948802
TI  - An integrative approach to cancer prevention through nutrition.

PMID- 22948803
TI  - Generation of monoclonal antibodies against the Galbeta1-4Gal epitope: a key tool
      in studies of species-specific glycans expressed in fish, amphibians and birds.
AB  - Whereas the Galbeta1-4Gal epitope is rarely found in mammalian glycans, it has
      been found in glycans of various species of non-mammalian vertebrates, such as
      fish, amphibians and birds. Although glycans containing Galbeta1-4Gal in these
      vertebrates were detected by precise structural analysis of the glycans using
      mass spectrometry and/or NMR spectrometry, there are no convenient methods to
      detect Galbeta1-4Gal from various samples. To analyze systematically the
      distribution of Galbeta1-4Gal in nature, we generated mouse monoclonal antibodies
      (mAbs) specific for Galbeta1-4Gal using extracts of medaka eggs as an immunogen.
      Four mAbs (two immunoglobulin (Ig)Ms and two IgG1s) were obtained by enzyme
      linked immunosorbent assay-based screening. The specificities of these mAbs were
      evaluated by frontal affinity chromatography using 142 kinds of 2-aminopyridine
      (PA)-derivatized oligosaccharides. While all mAbs interacted with (Galbeta1-4Gal)
      containing oligosaccharides at their non-reducing termini with dissociation
      constants (K(d)) ranging from 1.0 x 10-5 to 2.8 x 10-4 M, no apparent interaction
      was observed with any other glycans. The number of branches containing Galbeta1
      4Gal on N-glycans did not significantly affect K(d) of mAbs of IgG1 subclasses,
      but those of IgM mAbs were decreased by ~1 order of magnitude, in increments of
      the number of branches present. Using the mAbs, we established that Galbeta1-4Gal
      is also expressed on glycoproteins in various tissues from the African clawed
      frog. Immunohistochemical staining of medaka sections revealed that Galbeta1-4Gal
      epitopes were expressed in the endothelium, epithelium and epidermis, which
      directly contact the external environment or invading organisms. Thus, these mAbs
      are useful for systematically investigating the species-specific expression of
      glycans, which may act as a barrier against infection.

PMID- 22948804
TI  - Effects of ionic liquids on fluorescence characteristics of 17alpha- and 17beta
      estradiol.
AB  - Herein, we report the effects of six different room temperature ionic liquids
      (RTILs) on fluorescence spectra of 17alpha-estradiol (EE1) and 17beta-estradiol
      (E2). The selected RTILs belonged to the compound classes of 1-alkyl-3
      methylimidazolium tetrafluoroborate ([C(n)MIM]BF(4)) and 1-alkyl-3-methyl
      imidazolium hexafluorophosphate ([C(n)MIM]PF(6)). RTILs had a gradual quenching
      effect on fluorescence intensity (FI) of EE1 and E2, and the quenching process
      followed the well-known Stern-Volmer theory. The quenching mechanism of EE1 and
      E2 by RTILs was demonstrated to be dynamic quenching. Additionally, the overall
      quenching efficiency by [C(n)MIM]BF(4) was higher than [C(n)MIM]PF(6). The
      increased carbon chain length of RTILs did not lead to obvious differences in FI
      for EE1 and E2. The quenching efficiency showed irregular trend at three
      different temperatures (25, 35 and 45  degrees C). RTILs such as [C(4)MIM]PF(6)
      had the different fluorescent effects on organic chemicals with different
      fluorophores. The enhancing effects of [C(4)MIM]PF(6) were observed on strong
      fluorescence chemicals (dansyl chloride, rhrodamine B, 1,10-phenanthroline,
      norfloxacin), while quenching effect on weak fluorescence chemicals (EE1 and E2).
      In theory, these results provide a theoretical foundation for deep insight into
      their interaction mechanism between RTILs and estradiol.

PMID- 22948805
TI  - Diagnostic accuracy of two endocervical sampling method: randomized controlled
      trial.
AB  - OBJECTIVE: To compare the diagnostic accuracy of endocervical curettage (ECC) and
      endocervical brushing (EB) in patients referred for colposcopic evaluation for
      low grade squamous intraepithelial lesion. MATERIALS AND METHODS: A prospective,
      randomized, comparative trial was conducted in an Education and Research
      Hospital, Gynecologic Oncology Clinic. After exclusion of 40 subjects, 208
      patients were randomly allocated into ECC (n = 104) and EB (n = 104) groups. A
      pathologist blinded to the specimen obtaining method evaluated all samples for
      the primary outcome of sampling adequacy. Secondary outcome measure was pain
      scores during the sampling was investigated by using visual analogue scale (VAS).
      RESULTS: Ten samples from the ECC group (9.6 %) and 12 samples from the brushing
      group (12 %) contained scanty endocervical specimen (p = 0.09). Evaluating
      samples for stroma; it was reported that brushing group had a statistically
      significantly higher percentage of specimens with no stroma (44 %) than ECC group
      (24 %) (p = 0.003). Mean and standard deviation of VAS scores during the ECC and
      EB procedures were 2.55 +/- 1.12 and 1.99 +/- 0.87, respectively (p < 0.001).
      CONCLUSION: Endocervical brushing was proved to be as accurate with respect to
      diagnostic yield as ECC but less painful, evaluating the endocervical canal. It
      can be an alternative for evaluation of the cervical canal pathology in patients
      with low grade cytologic abnormalities but devoid of the misinterpretation of
      stromal invasion; ECC should be preferred in patients with a suspicion of
      invasive disease.

PMID- 22948806
TI  - Intramural ectopic pregnancy with live birth at 37 weeks of gestation.

PMID- 22948807
TI  - Redefining the major peanut allergens.
AB  - Food allergy has become a major public health concern in westernized countries,
      and allergic reactions to peanuts are particularly common and severe. Allergens
      are defined as antigens that elicit an IgE response, and most allergenic
      materials (e.g., pollens, danders, and foods) contain multiple allergenic
      proteins. This has led to the concept that there are "major" allergens and
      allergens of less importance. "Major allergens" have been defined as allergens
      that bind a large amount of IgE from the majority of patients and have biologic
      activity. However, the ability of an allergen to cross-link complexes of IgE and
      its high-affinity receptor FcepsilonRI (IgE/FcepsilonRI), which we have termed
      its allergic effector activity, does not correlate well with assays of IgE
      binding. To identify the proteins that are the most active allergens in peanuts,
      we and others have employed in vitro model assays of allergen-mediated cross
      linking of IgE/FcepsilonRI complexes and have demonstrated that the most potent
      allergens are not necessarily those that bind the most IgE. The importance of a
      specific allergen can be determined by measuring the allergic effector activity
      of that allergen following purification under non-denaturing conditions and by
      specifically removing the allergen from a complex allergenic extract either by
      chromatography or by specific immunodepletion. In our studies of peanut
      allergens, our laboratory has found that two related allergens, Ara h 2 and Ara h
      6, together account for the majority of the effector activity in a crude peanut
      extract. Furthermore, murine studies demonstrated that Ara h 2 and Ara h 6 are
      not only the major elicitors of anaphylaxis in this system, but also can
      effectively desensitize peanut-allergic mice. As a result of these observations,
      we propose that the definition of a major allergen should be based on the potency
      of that allergen in assays of allergic effector activity and demonstration that
      removal of that allergen from an extract results in loss of potency. Using these
      criteria, Ara h 2 and Ara h 6 are the major peanut allergens.

PMID- 22948808
TI  - Phenotype and function of protective, CD4-independent CD8 T cell memory.
AB  - While the need for CD4 T cells in the generation of CD8 T cell memory has been
      well documented, the mechanism underlying their requirement remains unknown.
      Here, we detail an immunization method capable of generating CD8 memory T cells
      that are indifferent to CD4 T cell help. Using a subunit vaccination that
      combines polyIC and an agonistic CD40 antibody, we program protective CD4
      independent CD8 T cell memory. When cells generated by combined polyIC/CD40
      immunization are compared to cells produced following a CD4-dependent
      vaccination, Listeria monocytogenes, they display dramatic differences, both
      phenotypically and functionally. The memory cells generated in a CD4-deficient
      host by polyIC/CD40 immunization provide protection against secondary infectious
      challenge, whereas cells generated by LM immunization in the same environment do
      not. Interestingly, combined polyIC/CD40 immunization generates long-term memory
      cells with low Blimp-1 and elevated Eomes expression despite high expression of
      Blimp-1 during the primary response. The potency of combined polyIC/CD40 to
      elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be
      considered as a vaccine adjuvant in clinical situations where CD4
      responses/numbers are compromised.

PMID- 22948809
TI  - In vivo distribution and antitumor effect of infused immune cells in a gastric
      cancer model.
AB  - Adoptive cellular transfer has been employed for cancer immunotherapy, including
      patients with gastric cancer. However, little is known about the distribution of
      effector cells after their injection via different pathways. In this study, we
      used human gastric cancer cells (BGC823) tagged with enhanced green fluorescent
      protein (EGPF) to establish a subcutaneous gastric cancer model in nude mice.
      Cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) were
      generated from human peripheral blood and labeled with red fluorescent PKH26. A
      portion of CIK cells was armed with CEA/CD3-bispecific single-chain antibody.
      When CIK cells were injected into nude mice with established subcutaneous gastric
      cancer via peritumoral (p.t.), intravenous (i.v.) and intraperitoneal (i.p.)
      infusion respectively, the distribution of cells was observed using a live
      fluorescence imaging system. We found that only a very small number of CIK cells
      could travel to the tumor site after i.p. or i.v. infusion, and they inhibited
      subcutaneous tumor growth in vivo only immediately following injection. In
      contrast, p.t. injection resulted in a significantly higher accumulation of CIK
      cells at the tumor site for 48 hours and mediated the greatest tumor inhibition
      compared with the other two injection methods. In addition, we compared the
      antitumor activity of CIK, CEA/CD3-bscAb-CIK and CTL cells in vitro and in vivo
      after p.t. injection. Among the three types of immune cells, CTLs demonstrated
      the strongest antitumor activity both in vitro and in vivo. CEA/CD3-bispecific
      single chain antibody could effectively link T lymphocytes and tumor cells
      expressing CEA, and resulted in significantly higher accumulation of CIK cells at
      the tumor site compared with the parental CIK cells. This study indicates that
      peritumoral injection of immune effector cells by minimally invasive surgical
      procedures represents an effective delivery method of adoptive cellular
      immunotherapy. Tumor-specific immune cells, such as CTLs, are a better choice of
      effector cells than CIKs in cellular immunotherapy. Furthermore, CD3+ immune
      cells armed with the CEA/CD3-bispecific single chain antibody could more
      effectively travel to and accumulate at the site of tumors expressing CEA, such
      as gastric cancer.

PMID- 22948810
TI  - Potential pitfalls in imaging of paediatric cerebral sinovenous thrombosis.
AB  - Paediatric cerebral sinovenous thrombosis (CSVT) is a rare but serious condition.
      The imaging signs may be subtle with a number of potential pitfalls. We present a
      pictorial essay of the pitfalls of diagnosis of CSVT on CT and MRI. We describe,
      using examples, potential pitfalls on both imaging modalities including
      anatomical variants of the cerebral venous system, extra-axial fluid collections
      and enhancement of chronic thrombus. Pitfalls particular to CT are discussed
      including beam-hardening artefact, image windowing and neonatal physiological
      intravascular hyperdensity. We review the potential variability in the appearance
      of thrombus on MRI, dependent largely on the stage of thrombus evolution and the
      pulse sequence. The signal intensity of thrombi, although described as evolving
      in a typical pattern on T1- and T2-weighted MRI, may be affected by variability
      in the degree of oxygenation of red cells in the forming thrombus, dilution and
      secondary propagation of thrombosis. Individual MRI sequences should not be
      interpreted in isolation, but as a set, and compared with CT images if available.

PMID- 22948811
TI  - Markov model of CLL transplants.

PMID- 22948812
TI  - Social inclusion of people with severe mental illness living in community housing
      programs.
AB  - OBJECTIVE: The authors investigated levels of social inclusion among service
      users of two types of psychiatric community housing programs in the Netherlands.
      METHODS: A large-scale cross-sectional survey was conducted that included service
      users of community housing programs (N=255) and their key workers (N=75). Data on
      social inclusion-participating in activities, receiving and making visits, and
      vocational participation-were collected through a service user diary. Univariate
      regression analyses were performed with the social inclusion variables as the
      dependent variables and type of housing program (supported independent living
      versus residential care) as the independent variable. RESULTS: Service users
      living independently were more likely to feel socially included, in terms of
      activities and visits, than residents. Type of housing program was not associated
      with vocational participation. CONCLUSIONS: Although service users living
      independently were more likely than residents to be socially included, their
      vocational participation was similar to that of residents. It seems that for both
      groups of service user, it is important to improve the availability of vocational
      interventions or programs.

PMID- 22948814
TI  - Combination of mangiferin and dipeptidyl peptidase-4 inhibitor sitagliptin
      improves impaired glucose tolerance in streptozotocin-diabetic rats.
AB  - In this study, we combined the dipeptidyl peptidase-4 inhibitor sitagliptin with
      the antidiabetic drug mangiferin to examine the effects on active glucagon-like
      peptide-1 (GLP-1) and glucose tolerance in streptozotocin-diabetic rats. Active
      GLP-1 levels were measured by an ELISA kit. Insulin levels were measured by an
      RIA kit. Islet morphology was determined by double immunolabeling. Sitagliptin (1
      mg/kg) or mangiferin (20 mg/kg) single treatment improved glucose tolerance
      during an oral glucose tolerance test. In addition, the combination therapy
      improved glucose tolerance with an increase in plasma insulin level and active
      GLP-1 levels. Islets from combination-treated diabetic rats had markedly
      increased beta-cell/islet area ratio compared with islets from the diabetic or
      single-treatment rats. In conclusion, these results indicate that the combination
      therapy is useful as a therapeutic agent for impaired glucose tolerance and type
      2 diabetes.

PMID- 22948813
TI  - Subventricular zone localized irradiation affects the generation of proliferating
      neural precursor cells and the migration of neuroblasts.
AB  - Radiation therapy is a part of the standard treatment for brain tumor patients,
      often resulting in irreversible neuropsychological deficits. These deficits may
      be due to permanent damage to the neural stem cell (NSC) niche, damage to local
      neural progenitors, or neurotoxicity. Using a computed tomography-guided
      localized radiation technique, we studied the effects of radiation on NSC
      proliferation and neuroblast migration in the mouse brain. Localized irradiation
      of the subventricular zone (SVZ) eliminated the proliferating neural precursor
      cells and migrating neuroblasts. After irradiation, type B cells in the SVZ
      lacked the ability to generate migrating neuroblasts. Neuroblasts from the
      unirradiated posterior SVZ did not follow their normal migratory path through the
      irradiated anterior SVZ. Our results indicate that the migrating neuroblasts were
      not replenished, despite the presence of type B cells in the SVZ post
      irradiation. This study provides novel insights into the effects of localized SVZ
      radiation on neurogenesis and cell migration that may potentially lead to the
      development of new radiotherapy strategies to minimize damage to NSCs and
      neuroblast migration.

PMID- 22948817
TI  - Hard magnetic ferrite with a gigantic coercivity and high frequency millimetre
      wave rotation.
AB  - Magnetic ferrites such as Fe(3)O(4) and Fe(2)O(3) are extensively used in a range
      of applications because they are inexpensive and chemically stable. Here we show
      that rhodium-substituted epsilon-Fe(2)O(3), epsilon-Rh(x)Fe(2-x)O(3) nanomagnets
      prepared by a nanoscale chemical synthesis using mesoporous silica as a template,
      exhibit a huge coercive field (H(c)) of 27 kOe at room temperature. Furthermore,
      a crystallographically oriented sample recorded an H(c) value of 31 kOe, which is
      the largest value among metal-oxide-based magnets and is comparable to those of
      rare-earth magnets. In addition, epsilon-Rh(x)Fe(2-x)O(3) shows high frequency
      millimetre wave absorption up to 209 GHz. epsilon-Rh(0.14)Fe(1.86)O(3) exhibits a
      rotation of the polarization plane of the propagated millimetre wave at 220 GHz,
      which is one of the promising carrier frequencies (the window of air) for
      millimetre wave wireless communications.

PMID- 22948815
TI  - Chemical methods to interrogate bacterial quorum sensing pathways.
AB  - Bacteria frequently manifest distinct phenotypes as a function of cell density in
      a phenomenon known as quorum sensing (QS). This intercellular signalling process
      is mediated by "chemical languages" comprised of low-molecular weight signals,
      known as autoinducers, and their cognate receptor proteins. As many of the
      phenotypes regulated by QS can have a significant impact on the success of
      pathogenic or mutualistic prokaryotic-eukaryotic interactions, there is
      considerable interest in methods to probe and modulate QS pathways with temporal
      and spatial control. Such methods would be valuable for both basic research in
      bacterial ecology and in practical medicinal, agricultural, and industrial
      applications. Toward this goal, considerable recent research has been focused on
      the development of chemical approaches to study bacterial QS pathways. In this
      Perspective, we provide an overview of the use of chemical probes and techniques
      in QS research. Specifically, we focus on: (1) combinatorial approaches for the
      discovery of small molecule QS modulators, (2) affinity chromatography for the
      isolation of QS receptors, (3) reactive and fluorescent probes for QS receptors,
      (4) antibodies as quorum "quenchers," (5) abiotic polymeric "sinks" and "pools"
      for QS signals, and (6) the electrochemical sensing of QS signals. The
      application of such chemical methods can offer unique advantages for both
      elucidating and manipulating QS pathways in culture and under native conditions.

PMID- 22948816
TI  - Extracellular ATP mediates mast cell-dependent intestinal inflammation through
      P2X7 purinoceptors.
AB  - Mast cells are known effector cells in allergic and inflammatory diseases, but
      their precise roles in intestinal inflammation remain unknown. Here we show that
      activation of mast cells in intestinal inflammation is mediated by ATP-reactive
      P2X7 purinoceptors. We find an increase in the numbers of mast cells expressing
      P2X7 purinoceptors in the colons of mice with colitis and of patients with
      Crohn's disease. Treatment of mice with a P2X7 purinoceptor-specific antibody
      inhibits mast cell activation and subsequent intestinal inflammation. Similarly,
      intestinal inflammation is ameliorated in mast cell-deficient Kit(W-sh/W-sh)
      mice, and reconstitution with wild-type, but not P2x7(-/-) mast cells results in
      susceptibility to inflammation. ATP-P2X7 purinoceptor-mediated activation of mast
      cells not only induces inflammatory cytokines, but also chemokines and
      leukotrienes, to recruit neutrophils and subsequently exacerbate intestinal
      inflammation. These findings reveal the role of P2X7 purinoceptor-mediated mast
      cell activation in both the initiation and exacerbation of intestinal
      inflammation.

PMID- 22948818
TI  - Blind topological measurement-based quantum computation.
AB  - Blind quantum computation is a novel secure quantum-computing protocol that
      enables Alice, who does not have sufficient quantum technology at her disposal,
      to delegate her quantum computation to Bob, who has a fully fledged quantum
      computer, in such a way that Bob cannot learn anything about Alice's input,
      output and algorithm. A recent proof-of-principle experiment demonstrating blind
      quantum computation in an optical system has raised new challenges regarding the
      scalability of blind quantum computation in realistic noisy conditions. Here we
      show that fault-tolerant blind quantum computation is possible in a topologically
      protected manner using the Raussendorf-Harrington-Goyal scheme. The error
      threshold of our scheme is 4.3 * 10(-3), which is comparable to that (7.5 * 10(
      3)) of non-blind topological quantum computation. As the error per gate of the
      order 10(-3) was already achieved in some experimental systems, our result
      implies that secure cloud quantum computation is within reach.

PMID- 22948819
TI  - Ultrafast magnetization enhancement in metallic multilayers driven by
      superdiffusive spin current.
AB  - Uncovering the physical mechanisms that govern ultrafast charge and spin dynamics
      is crucial for understanding correlated matter as well as the fundamental limits
      of ultrafast spin-based electronics. Spin dynamics in magnetic materials can be
      driven by ultrashort light pulses, resulting in a transient drop in magnetization
      within a few hundred femtoseconds. However, a full understanding of femtosecond
      spin dynamics remains elusive. Here we spatially separate the spin dynamics using
      Ni/Ru/Fe magnetic trilayers, where the Ni and Fe layers can be ferro- or
      antiferromagnetically coupled. By exciting the layers with a laser pulse and
      probing the magnetization response simultaneously but separately in Ni and Fe, we
      surprisingly find that optically induced demagnetization of the Ni layer
      transiently enhances the magnetization of the Fe layer when the two layer
      magnetizations are initially aligned parallel. Our observations are explained by
      a laser-generated superdiffusive spin current between the layers.

PMID- 22948820
TI  - Lysine methylation of VCP by a member of a novel human protein methyltransferase
      family.
AB  - Valosin-containing protein (VCP, also called p97) is an essential and highly
      conserved adenosine triphosphate-dependent chaperone implicated in a wide range
      of cellular processes in eukaryotes, and mild VCP mutations can cause severe
      neurodegenerative disease. Here we show that mammalian VCP is trimethylated on
      Lys315 in a variety of cell lines and tissues, and that the previously
      uncharacterized protein METTL21D (denoted here as VCP lysine methyltransferase,
      VCP-KMT) is the responsible enzyme. VCP methylation was abolished in three human
      VCP-KMT knockout cell lines generated with zinc-finger nucleases. Interestingly,
      VCP-KMT was recently reported to promote tumour metastasis, and indeed, VCP-KMT
      deficient cells displayed reduced growth rate, migration and invasive potential.
      Finally, we present data indicating that VCP-KMT, calmodulin-lysine
      methyltransferase and eight uncharacterized proteins together constitute a novel
      human protein methyltransferase family. The present work provides new insights on
      protein methylation and its links to human disease.

PMID- 22948821
TI  - Naphthol radical couplings determine structural features and enantiomeric excess
      of dalesconols in Daldinia eschscholzii.
AB  - Understanding how simple molecules are pieced together in organisms may aid
      biotechnological manipulation and synthetic approaches to complex natural
      products. The mantis-associated fungus Daldinia eschscholzii IFB-TL01 produces
      the unusually structured immunosuppressants (+/-)-dalesconols A and B, along with
      their congener (+/-)-dalesconol C, with the (-)-enantiomers in excess. Here we
      report that these structural and stereochemical peculiarities of dalesconols A-C
      are a result of promiscuous and atropselective couplings of radicals derived from
      1,3,6,8-tetrahydroxynaphthalene, 1,3,8-trihydroxynaphthalene and 1,8
      dihydroxynaphthalene. The observed (-)-enantiomeric excess is found to depend on
      the dominance of particular conformers of naphthol dimer intermediates, which are
      ligands of laccase.

PMID- 22948822
TI  - Phase-locking to a free-space terahertz comb for metrological-grade terahertz
      lasers.
AB  - Optical frequency comb synthesizers have represented a revolutionary approach to
      frequency metrology, providing a grid of frequency references for any laser
      emitting within their spectral coverage. Extending the metrological features of
      optical frequency comb synthesizers to the terahertz domain would be a major
      breakthrough, due to the widespread range of accessible strategic applications
      and the availability of stable, high-power and widely tunable sources such as
      quantum cascade lasers. Here we demonstrate phase-locking of a 2.5 THz quantum
      cascade laser to a free-space comb, generated in a LiNbO(3) waveguide and
      covering the 0.1-6 THz frequency range. We show that even a small fraction (<100
      nW) of the radiation emitted from the quantum cascade laser is sufficient to
      generate a beat note suitable for phase-locking to the comb, paving the way to
      novel metrological-grade terahertz applications, including high-resolution
      spectroscopy, manipulation of cold molecules, astronomy and telecommunications.

PMID- 22948823
TI  - The amniote paratympanic organ develops from a previously undiscovered sensory
      placode.
AB  - The paratympanic organ, a mechanosensory hair cell-containing pouch in the
      amniote middle ear, was first described 100 years ago, yet its origins remain
      unresolved. Homology with the anamniote spiracular organ is supported by
      association with homologous skeletal elements and similar central targets of
      afferent neurons, suggesting it might be a remnant of the water-dependent lateral
      line system, otherwise lost during the amniote transition to terrestrial life.
      However, this is incompatible with studies suggesting that it arises from the
      first epibranchial (geniculate) placode. Here we show that a previously
      undiscovered Sox2-positive placode, immediately dorsal to the geniculate placode,
      forms the paratympanic organ and its afferent neurons, which are molecularly and
      morphologically distinct from geniculate neurons. These data remove the only
      obstacle to accepting the homology of the paratympanic organ and spiracular
      organ. We hypothesize that the paratympanic organ/spiracular organ represents an
      ancient head ectoderm module, developmentally and evolutionarily independent of
      both lateral line and epibranchial placodes.

PMID- 22948824
TI  - Discovery of acetylene hydratase activity of the iron-sulphur protein IspH.
AB  - The final step of the methylerythritol phosphate isoprenoid biosynthesis pathway
      is catalysed by the iron-sulphur enzyme IspH, producing the universal precursors
      of terpenes: isopentenyl diphosphate and dimethylallyl diphosphate. Here we
      report an unforeseen reaction discovered during the investigation of the
      interaction of IspH with acetylene inhibitors by X-ray crystallography,
      Mobetabauer, and nuclear magnetic resonance spectroscopy. In addition to its role
      as a 2H(+)/2e(-) reductase, IspH can hydrate acetylenes to aldehydes and ketones
      via anti-Markovnikov/Markovnikov addition. The reactions only occur with the
      oxidised protein and proceed via eta(1)-O-enolate intermediates. One of these is
      characterized crystallographically and contains a C4 ligand oxygen bound to the
      unique, fourth iron in the 4Fe-4S cluster: this intermediate subsequently
      hydrolyzes to produce an aldehyde product. This unexpected side to IspH
      reactivity is of interest in the context of the mechanism of action of other
      acetylene hydratases, as well as in the design of antiinfectives targeting IspH.

PMID- 22948825
TI  - Spin-enhanced organic bulk heterojunction photovoltaic solar cells.
AB  - Recently, much effort has been devoted to improve the efficiency of organic
      photovoltaic solar cells based on blends of donors and acceptors molecules in
      bulk heterojunction architecture. One of the major losses in organic photovoltaic
      devices has been recombination of polaron pairs at the donor-acceptor domain
      interfaces. Here, we present a novel method to suppress polaron pair
      recombination at the donor-acceptor domain interfaces and thus improve the
      organic photovoltaic solar cell efficiency, by doping the device active layer
      with spin 1/2 radical galvinoxyl. At an optimal doping level of 3 wt%, the
      efficiency of a standard poly(3-hexylthiophene)/1-(3-(methoxycarbonyl)propyl)-1-1
      phenyl)(6,6)C(61) solar cell improves by 18%. A spin-flip mechanism is proposed
      and supported by magneto-photocurrent measurements, as well as by density
      functional theory calculations in which polaron pair recombination rate is
      suppressed by resonant exchange interaction between the spin 1/2 radicals and
      charged acceptors, which convert the polaron pair spin state from singlet to
      triplet.

PMID- 22948827
TI  - Efficacy of the beta2-adrenergic receptor is determined by conformational
      equilibrium in the transmembrane region.
AB  - Many drugs that target G-protein-coupled receptors (GPCRs) induce or inhibit
      their signal transduction with different strengths, which affect their
      therapeutic properties. However, the mechanism underlying the differences in the
      signalling levels is still not clear, although several structures of GPCRs
      complexed with ligands determined by X-ray crystallography are available. Here we
      utilized NMR to monitor the signals from the methionine residue at position 82 in
      neutral antagonist- and partial agonist-bound states of beta(2)-adrenergic
      receptor (beta(2)AR), which are correlated with the conformational changes of the
      transmembrane regions upon activation. We show that this residue exists in a
      conformational equilibrium between the inverse agonist-bound states and the full
      agonist-bound state, and the population of the latter reflects the signal
      transduction level in each ligand-bound state. These findings provide insights
      into the multi-level signalling of beta(2)AR and other GPCRs, including the basal
      activity, and the mechanism of signal transduction mediated by GPCRs.

PMID- 22948826
TI  - The allosteric vestibule of a seven transmembrane helical receptor controls G
      protein coupling.
AB  - Seven transmembrane helical receptors (7TMRs) modulate cell function via
      different types of G proteins, often in a ligand-specific manner. Class A 7TMRs
      harbour allosteric vestibules in the entrance of their ligand-binding cavities,
      which are in the focus of current drug discovery. However, their biological
      function remains enigmatic. Here we present a new strategy for probing and
      manipulating conformational transitions in the allosteric vestibule of label-free
      7TMRs using the M(2) acetylcholine receptor as a paradigm. We designed dualsteric
      agonists as 'tailor-made' chemical probes to trigger graded receptor activation
      from the acetylcholine-binding site while simultaneously restricting spatial
      flexibility of the receptor's allosteric vestibule. Our findings reveal for the
      first time that a 7TMR's allosteric vestibule controls the extent of receptor
      movement to govern a hierarchical order of G-protein coupling. This is a new
      concept assigning a biological role to the allosteric vestibule for controlling
      fidelity of 7TMR signalling.

PMID- 22948828
TI  - Evidence for methane production by saprotrophic fungi.
AB  - Methane in the biosphere is mainly produced by prokaryotic methanogenic archaea,
      biomass burning, coal and oil extraction, and to a lesser extent by eukaryotic
      plants. Here we demonstrate that saprotrophic fungi produce methane without the
      involvement of methanogenic archaea. Fluorescence in situ hybridization, confocal
      laser-scanning microscopy and quantitative real-time PCR confirm no contribution
      from microbial contamination or endosymbionts. Our results suggest a common
      methane formation pathway in fungal cells under aerobic conditions and thus
      identify fungi as another source of methane in the environment. Stable carbon
      isotope labelling experiments reveal methionine as a precursor of methane in
      fungi. These findings of an aerobic fungus-derived methane formation pathway open
      another avenue in methane research and will further assist with current efforts
      in the identification of the processes involved and their ecological
      implications.

PMID- 22948829
TI  - The use of the sex pheromone as an evolutionary solution to food source selection
      in caterpillars.
AB  - Sex pheromones are released by adults of a species to elicit a sexual interaction
      with the other sex of the same species. Here we report an unexpected effect of a
      moth sex pheromone on the caterpillars of the same species. We demonstrate that
      larvae of the cotton leafworm Spodoptera littoralis are attracted by the moth sex
      pheromone and that this phenomenon is independent of sex determination. In
      addition, we show that the olfactory sensilla carried by the caterpillar antennae
      are sensitive to the pheromone and that the caterpillar sensilla express
      pheromone-binding proteins that are used by adult antennae to bind pheromone
      components. Finally, we demonstrate that the larvae are preferentially attracted
      to a food source when it contains the sex pheromone main component. A possible
      interpretation of these results is that the sex pheromone is used to promote food
      search in caterpillars, opening potential new routes for insect pest management.

PMID- 22948830
TI  - Reconstructing plate-motion changes in the presence of finite-rotations noise.
AB  - Understanding lithospheric plate motions is of paramount importance to
      geodynamicists. Much effort is going into kinematic reconstructions featuring
      progressively finer temporal resolution. However, the challenge of precisely
      identifying ocean-floor magnetic lineations, and uncertainties in geomagnetic
      reversal timescales result in substantial finite-rotations noise. Unless some
      type of temporal smoothing is applied, the scenario arising at the native
      temporal resolution is puzzling, as plate motions vary erratically and
      significantly over short periods (<1 Myr). This undermines our ability to make
      geodynamic inferences, as the rates at which forces need to be built upon plates
      to explain these kinematics far exceed the most optimistic estimates. Here we
      show that the largest kinematic changes reconstructed across the Atlantic, Indian
      and South Pacific ridges arise from data noise. We overcome this limitation using
      a trans-dimensional hierarchical Bayesian framework. We find that plate-motion
      changes occur on timescales no shorter than a few million years, yielding simpler
      kinematic patterns and more plausible dynamics.

PMID- 22948832
TI  - Eduard Strasburger--dead for a century, but still alive.

PMID- 22948831
TI  - The intergenic spacer region of the rDNA in Haplopappus gracilis (Nutt.) Gray.
AB  - In this paper, we provide further information on the genome organisation of
      Haplopappus gracilis, one of the six angiosperms showing the lowest chromosome
      number, i.e. 2n = 4, by determining the nucleotide sequence of the intergenic
      spacer region of the ribosomal RNA genes and its cytological localization on
      metaphase chromosomes. DNA sequence analysis reveals the occurring of a product
      of 4,382 bp in length, characterised by the presence of four blocks of different
      repeated sequences. Our analysis also evidenced putative promoter regions with
      three transcription initiation sites for polymerase I, as previously reported in
      Artemisia absinthium, belonging to the same Asteraceae family. A fluorescent in
      situ hybridization with the intergenic spacer probe indicates the presence of
      rDNA genes only in the satellited chromosomes of H. gracilis; besides,
      differences in the signal intensity between homologous chromosomes were
      frequently observed, thus suggesting for these chromosome sites the presence of a
      variable number of rDNA gene copies, even if a divergent chromatin organisation
      in corresponding regions cannot be ruled out.

PMID- 22948833
TI  - The impact of MRSA colonization on surgical site infection following major
      gastrointestinal surgery.
AB  - PURPOSE: The purpose of this study is to determine whether methicillin-resistant
      Staphylococcus aureus (MRSA) colonization affects surgical site infections (SSI)
      after major gastrointestinal (GI) operations. METHODS: We retrospectively
      reviewed the charts of all patients undergoing major GI surgery from December
      2007 to August 2009. All patients were tested for MRSA colonization and grouped
      according to results (MRSA+, methicillin-sensitive S. aureus [MSSA]+, and
      negative). Data analyzed included demographics, incidence of SSI, and wound
      culture results. RESULTS: A total of 1,137 patients were identified; 78.9 %
      negative, 14.7 % MSSA+, and 6.4 % MRSA+. The mean age was 59.5 years, 44.5 % of
      the patients were men, and 47.9 % of the patients underwent colorectal operation.
      SSI was identified in 101 (8.9 %) patients and was higher in the MRSA+ group than
      the negative and MSSA+ groups (13.7 vs. 9.4 vs. 4.2 %; p < 0.05). Although MRSA
      colonization had an odds ratio of 1.43 for developing an SSI, it was not a
      significant independent risk factor. However, the MRSA+ group was strongly
      associated with MRSA cultured from the wound when SSI was present (70 vs. 8.5 %;
      p < 0.0001). CONCLUSIONS: MRSA colonization is not an independent risk factor for
      SSI following major GI operations; however, it is strongly predictive of MRSA
      associated SSI in these patients. Preoperative MRSA nasal swab test with
      decolonization may reduce the incidence of MRSA-associated SSI after major GI
      surgery.

PMID- 22948834
TI  - Epigenetic modulation by methionine deficiency attenuates the potential for
      gastric cancer cell dissemination.
AB  - INTRODUCTION: Methionine dependency occurs frequently in tumor cells. Here we
      have investigated the effect of methionine deficiency on metastatic potential of
      gastric cancer cells in vitro and in vivo. MATERIALS AND METHODS: Model of
      peritoneal carcinomatosis and xenograft was generated by intraperitoneal or
      subcutaneous implantation of gastric cancer cells in NOD-SCID mice. In comparison
      to control medium, 3-day culture of MKN45, MKN74, and KATOIII cells in a
      methionine-deficient medium inhibited cell proliferation, increased the rate of
      cell apoptosis, and reduced cell adhesion and migration. In the xenograft model
      induced by implantation of MNK45 and MNK74 cells, two cycles of methionine
      deficient diet reduced the tumor growth. Further on, a 10-day cycle of methionine
      deficient diet reduced the number of peritoneal nodules in the model of
      peritoneal carcinomatosis induced by MKN45 cells injection. Finally, a microarray
      analysis of the methylation of promoter CpG islets demonstrated that methionine
      deficiency reduced the promoter methylation of E-cadherin whose expression was
      markedly increased in vivo and in vitro. RESULTS: In summary, we have provided
      evidence that a methionine-deficient diet modulates the growth of gastric tumor
      cells and in vitro deficiency of methionine increased apoptosis and decreased
      cellular adhesion and migration associated to epigenetic change of E-cadherin
      gene, in vivo and in vitro.

PMID- 22948835
TI  - Effect of the artificial sweetener, acesulfame potassium, a sweet taste receptor
      agonist, on glucose uptake in small intestinal cell lines.
AB  - INTRODUCTION: Sweet taste receptors may enhance glucose absorption. AIM: This
      study aimed to explore the cell biology of sweet taste receptors on glucose
      uptake. HYPOTHESIS: Artificial sweeteners increase glucose uptake via activating
      sweet taste receptors in the enterocyte to translocate GLUT2 to the apical
      membrane through the PLC betaII pathway. METHODS: Caco-2, RIE-1, and IEC-6 cells,
      starved from glucose for 1 h were pre-incubated with 10 mM acesulfame potassium
      (AceK). Glucose uptake was measured by incubating cells for 1 to 10 min with 0.5
      50 mM glucose with or without U-73122, chelerythrine, and cytochalasin B.
      RESULTS: In Caco-2 and RIE-1 cells, 10 mM AceK increased glucose uptake by 20-30
      % at glucose >25 mM, but not in lesser glucose concentrations (<10 mM), nor at 1
      min or 10 min incubations. U-73122 (PLC betaII inhibitor) inhibited uptake at
      glucose >25 mM and for 5 min incubation; chelerythrine and cytochalasin B had
      similar effects. No effect occurred in IEC-6 cells. Activation of sweet taste
      receptors had no effect on glucose uptake in low (<25 mM) glucose concentrations
      but increased uptake at greater concentrations (>25 mM). CONCLUSIONS: Role of
      artificial sweeteners on glucose uptake appears to act in part by effects on the
      enterocyte itself.

PMID- 22948836
TI  - Improved long-term survival after major resection for hepatocellular carcinoma: a
      multicenter analysis based on a new definition of major hepatectomy.
AB  - BACKGROUND: Advances in the surgical management of hepatocellular carcinoma (HCC)
      have expanded the indications for curative hepatectomy, including more extensive
      liver resections. The purpose of this study was to examine long-term survival
      trends for patients treated with major hepatectomy for HCC. PATIENTS AND METHODS:
      Clinicopathologic data for 1,115 patients with HCC who underwent hepatectomy
      between 1981 and 2008 at five hepatobiliary centers in France, China, and the USA
      were assessed. In addition to other performance metrics, outcomes were evaluated
      using resection of >=4 liver segments as a novel definition of major hepatectomy.
      RESULTS: Major hepatectomy was performed in 539 patients. In the major
      hepatectomy group, median tumor size was 10 cm (range: 1-27 cm) and 22 % of the
      patients had bilateral lesions. The TNM Stage distribution included 29 % Stage I,
      31 % Stage II, 38 % Stage III, and 2 % Stage IV. The postoperative histologic
      examination indicated that chronic liver disease was present in 35 % of the
      patients and tumor microvascular invasion was identified in 60 % of the patients.
      The 90-day postoperative mortality rate was 4 %. After a median follow-up time of
      63 months, the 5-year overall survival rate was 40 %. Patients treated with right
      hepatectomy (n = 332) and those requiring extended hepatectomy (n = 207) had
      similar 90-day postoperative mortality rates (4 % and 4 %, respectively, p =
      0.976) and 5-year overall survival rates (42 % and 36 %, respectively, p =
      0.523). Postoperative mortality and overall survival rates after major
      hepatectomy were similar among the participating countries (p > 0.1) and improved
      over time with 5-year survival rates of 30 %, 40 %, and 51 % for the years 1981
      1989, 1990-1999, and the most recent era of 2000-2008, respectively (p = 0.004).
      In multivariate analysis, factors that were significantly associated with worse
      survivals included AFP level >1,000 ng/mL, tumor size >5 cm, presence of major
      vascular invasion, presence of extrahepatic metastases, positive surgical
      margins, and earlier time period in which the major hepatectomy was performed.
      CONCLUSIONS: This multinational, long-term HCC survival analysis indicates that
      expansion of surgical indications to include major hepatectomy is justified by
      the significant improvement in outcomes over the past three decades observed in
      both the East and the West.

PMID- 22948837
TI  - A preoperative nomogram to predict the risk of perioperative mortality following
      gastric resections for malignancy.
AB  - INTRODUCTION: Surgery remains one of the major treatment options available to
      patients with gastric cancer. The aim of this study was to develop a preoperative
      nomogram based on the presence of comorbidities to predict the risk of
      perioperative mortality following gastric resections for malignancy. METHODS: The
      Nationwide Inpatient Sample (NIS) database was used to create a nomogram using
      SAS software. The training set (years 1993, 1996-97, 1999-2000, 2002, 2004-05)
      was used to develop the model which was further validated using the validation
      set (years 1994-95, 1998, 2001, and 2003). RESULTS: A total of 14,235 and 9,404
      patients were included in the training and validation sets, respectively, with
      overall actual observed perioperative mortality rates of 5.9 % and 6.6 %,
      respectively. The decile-based calibration plots for the training and validation
      sets revealed a good agreement between the observed and nomogram-predicted
      probabilities. The accuracy of the nomogram was further reinforced by a
      concordance index of 0.75 (95 % confidence interval 0.73 to 0.77) which was
      calculated using the validation set. CONCLUSION: This preoperative nomogram may
      accurately predict the risk of perioperative mortality following gastric
      resections for malignancy and may be used as an adjunctive clinical tool in the
      preoperative counseling of these patients.

PMID- 22948838
TI  - Short-term outcomes of laparoscopy combined with enhanced recovery pathway after
      ileocecal resection for Crohn's disease: a case-matched analysis.
AB  - BACKGROUND: Laparoscopy combined with an enhanced recovery pathway (ERP) is
      widely considered to be the first-choice option for patients with colorectal
      cancer. However, no previous reports have focused on patients with Crohn's
      disease (CD) treated by laparoscopy and ERP. METHODS: Twenty patients with CD
      underwent laparoscopic ileocecal resection with an ERP at two institutions. The
      ERP protocol included no bowel preparation nor fasting, no nasogastric tube, no
      abdominal drains, early removal of urinary catheter, early solid dietary intake
      and mobilization, opioid-sparing analgesia and restrictive fluid management. This
      group was compared with a matched historical control group of 70 CD patients who
      underwent laparoscopic ileocecal resection treated with conventional care.
      RESULTS: Compliance with the ERP was high (>=80 %) for all items except no drain
      placement. A significantly earlier return of bowel function (time to first flatus
      and stool) was observed in the ERP group. Mean postoperative and total length of
      stay were significantly shorter in the ERP group. Postoperative complications
      were similar in both groups. CONCLUSIONS: This is the first reported experience
      of laparoscopy with ERP in CD patients and suggests that optimized perioperative
      care combined with minimally invasive techniques may lead to further improvements
      in surgical outcomes for CD patients.

PMID- 22948839
TI  - Surgical endoscopic vacuum therapy for anastomotic leakage and perforation of the
      upper gastrointestinal tract.
AB  - INTRODUCTION: Emergency operations for perforations and anastomotic leakage of
      the upper gastrointestinal tract are associated with a high overall morbidity and
      mortality rate. An endoscopic vacuum therapy (EVT) has been established
      successfully for anastomotic leakage after rectal resection but only limited data
      exist for EVT of the upper GI tract. METHODS: We report on a series of nine
      patients treated with EVT for defects of the upper intestinal tract between March
      2011 and May 2012. In four patients, initial endoscopic sponge placement was
      performed in combination with open surgical revision. Median follow-up was 189
      (range, 51-366) days. RESULTS: In total, 52 vacuum sponges were placed in upper
      GI defects of nine patients. Indication for EVT were anastomotic leakage after
      esophageal resection or gastrectomy (n = 5) and iatrogenic or spontaneous
      esophageal perforations (n = 4). The mean number of sponge insertions was six
      (range, 1-13) with a mean changing interval of 3.5 days (range, 2-5). A
      successful vacuum therapy for upper intestinal defects was achieved in eight of
      nine patients (89 %). CONCLUSION: EVT is a promising approach for postoperative,
      iatrogenic, or spontaneous lesions of the upper GI tract. If necessary the
      endoscopic procedure can be combined with operative revision for better control
      of the local septic focus.

PMID- 22948840
TI  - Meta-analysis of bioabsorbable staple line reinforcement and risk of fistula
      following pancreatic resection.
AB  - BACKGROUND: Stapled pancreatic transection is widely used although pancreatic
      fistula remains a common post-surgical complication. METHODS: We performed a meta
      analysis of existing data regarding pancreatic fistula following stapled
      pancreatic transection, comparing bare metal staples to reinforced staple loads.
      RESULTS: We identified ten manuscripts between 2007 and 2009 reporting outcomes
      following stapled division of the pancreas (five retrospective reviews, five
      prospective case series). A total of 483 stapled pancreatic resections are
      included in this meta-analysis. Of these, 234(48 %) were reinforced (REINF) and
      249 (52 %) were bare staples (STPL). Out of 483 cases, there were a total of 100
      documented pancreatic leaks (21 %). Sixty-one leaks were reported out of 249 STPL
      divisions (24 %), while 39 leaks were reported following REINF division (17 %).
      The overall relative risk of developing a pancreatic fistula following distal
      pancreatectomy was not significantly different comparing STPL to REINF when all
      studies were combined (RR 1.00, 95% CI 0.65-1.53). We further evaluated the data
      stratifying by study design (prospective or retrospective) and found that
      prospective studies reported a significantly higher risk of pancreatic fistula
      with STPL compared to REINF technique (RR 14.45, 95 % CI 3.15-66.21). CONCLUSION:
      Reinforced staples may be a preferred method of pancreatic stump closure
      following distal pancreatectomy.

PMID- 22948841
TI  - High-grade dysplasia and adenocarcinoma are frequent in side-branch intraductal
      papillary mucinous neoplasm measuring less than 3 cm on endoscopic ultrasound.
AB  - BACKGROUND: Surgical resection for intraductal papillary mucinous neoplasm (IPMN)
      of the pancreas has increased over the last decade. While IPMN with main duct
      communication are generally recommended for resection, indications for resection
      of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single
      institutional experience with SDIPMN and indications for resection. METHODS:
      Patients who underwent resection for IPMN were identified from a prospectively
      maintained IRB-approved database. Patients with main pancreatic duct
      communication were excluded. Outcome, clinical and pathologic characteristics
      were correlated with endoscopic ultrasound (EUS) findings. RESULTS: From 2000 to
      2010, 105 patients who underwent preoperative EUS evaluation and resection for
      SDIPMN were identified. The mean age was within the sixth decade of life, and
      there was a slight female predominance (55 vs. 45 %). The most common presenting
      symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %)
      and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at
      presentation; seven (70 %) had suspicious features on EUS. Of the total cohort,
      few patients had intracystic septations (N = 27, 26 %) or presence of mural
      nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal
      adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA)
      demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA
      findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size
      was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12
      (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed
      24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11
      %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35
      (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients
      with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of
      7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1-2 cm, and 10 of 44
      (23 %) with cyst size 2-3 cm. Seven of 35 (20 %) patients with cyst size >3 cm
      had high-grade dysplasia on final pathology. Although overall survival (OS) at 48
      months stratified by EUS cyst size did not significantly differ between groups,
      patients with PDAC on final pathology had significantly worse OS compared to
      noninvasive pathology. A total of eight patients (8 %) developed recurrent
      disease, all of whom had PDAC on final pathology. CONCLUSION: EUS is a helpful
      modality for the diagnostic evaluation of SDIPMN. Considering the high incidence
      of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS
      features should be used in conjunction with other clinical criteria to guide
      management decisions. Patients with SDIPMN greater than 2 cm that do not undergo
      surgical resection may benefit from more intensive surveillance.

PMID- 22948842
TI  - Hospital-level outcomes associated with laparoscopic colectomy for cancer in the
      minimally invasive era.
AB  - BACKGROUND: Compared to the open approach, randomized trials have shown that
      laparoscopic colectomy is associated with a shorter hospitalization without
      increases in morbidity or mortality rates. With broader adoption of laparoscopic
      colectomy for cancer in the USA, it is unclear if laparoscopic colectomy
      continues to be associated with shorter hospitalization and comparable morbidity.
      PURPOSE: The purpose of this study is to determine if hospitals where a greater
      proportion of colon resections for cancer are approached laparoscopically
      (laparoscopy rate) achieve improved short-term outcomes compared to hospitals
      with lower laparoscopy rates. METHODS: From the 2008-2009 Nationwide Inpatient
      Sample, we identified hospitals where <= 12 colon resections for cancer were
      reported with >= 1 approached laparoscopically. We assessed the correlation
      between a hospital's laparoscopy rate and risk-standardized outcomes (intra- and
      postoperative morbidity, in-hospital mortality rates, and average length of
      stay). RESULTS: Overall, 6,806 colon resections were performed at 276 hospitals.
      Variation was noted in hospital laparoscopy rates (median = 52.0 %, range = 3.8
      100 %) and risk-standardized intra- (2.7 %, 1.8-8.6 %) and postoperative
      morbidity (27.8 %, 16.4-53.4 %), in-hospital mortality (0.7 %, 0.3-42.0 %), and
      average length of stay (7.0 days, 4.9-10.3 days). While no association was noted
      with in-hospital mortality, higher laparoscopy rates were correlated with lower
      postoperative morbidity [correlation coefficient (r) = -0.12, p = 0.04) and
      shorter hospital stays (r  = -0.23, p  <  0.001), but higher intraoperative
      morbidity (r  =  0.19, p  <  0.001) rates. This was not observed among hospitals
      with high procedure volumes. CONCLUSIONS: Higher laparoscopy rates were
      associated with only slightly lower postoperative morbidity rates and modestly
      shorter hospitalizations.

PMID- 22948844
TI  - Japanese American wartime experience, Tamotsu Shibutani and methodological
      innovation, 1942-1978.
AB  - A case study of how wartime internment reverberated in the life and work of
      Japanese American intellectuals, this essay discusses the career and interests of
      Tamotsu Shibutani, a sociologist who began his training as part of Dorothy Swaine
      Thomas' Japanese American Evacuation and Resettlement Study (JERS). Though recent
      scholarship has noted some of the ethical problems that attended the use of
      Japanese American participant observers during the war, this essay concentrates
      instead on how interned intellectuals responded to their double role of both
      researcher (and intellectual) and object of study. I argue that in the case of
      Shibutani, his circumstances and identity shaped his scholarship, both as an
      academic endeavor and a political project. By tracking Shibutani's postwar
      scholarly activities, I show that his wartime experiences--as an internee,
      military officer, and participant-observer--reverberated in his sociological
      publications long after the war's end.

PMID- 22948843
TI  - Comparison between living donor liver transplantation recipients who met the
      Milan and UCSF criteria after successful downstaging therapies.
AB  - BACKGROUND AND AIMS: Various downstaging therapies were introduced to liver
      recipients who could not meet the relative criteria for liver transplantation,
      and many endpoints were reported. The most common criteria used were the Milan
      criteria and the University of California, San Francisco (UCSF) criteria.
      However, no comparison was made between them, and we attempted to find possible
      differences between the living donor liver transplantation (LDLT) patients who
      met the Milan criteria and those who met the UCSF criteria after accepting
      preoperative downstaging therapies. MATERIALS AND METHODS: We performed a
      retrospective study of all 72 patients at our center from January 2003 to March
      2009 who were diagnosed with advanced hepatocellular carcinoma but accepted
      various downstaging therapies. Some patients met the Milan criteria (group 1),
      and some met the UCSF criteria (group 2) but not the Milan criteria. We collected
      the data from the two groups and then compared the preoperative demographic data,
      downstaging therapies, intraoperative data from LDLT, and the recovery and
      complications after LDLT. Survival rates were compared using Kaplan-Meier
      analysis. RESULTS: Only 44 patients (61.1 %) met the criteria for liver
      transplantation, 21 cases met the Milan criteria (group 1), and 23 cases met the
      UCSF criteria (group 2) but not the Milan criteria. All of the 44 patients
      accepted right lobe living liver donor liver transplantation in our center. The
      difference in the baseline characteristics between the two groups did not reach
      statistical significance. The mean number of downstaging treatments per patient
      was 1.81 +/- 0.35 in group 1 and 1.83 +/- 0.41 in group 2 (P = 0.928). Most of
      the patients received only one downstaging treatment, and transcatheter arterial
      chemoembolization (TACE) was the most common downstaging therapy. Four patients
      suffered complications after downstaging therapies: intra-abdominal hemorrhage
      after right hepatectomy, upper gastrointestinal hemorrhage after TACE, biliary
      fistula after resection, and hand-foot syndrome after taking sorafenib. All
      complications after LDLT, classified according to the Clavien-Dindo system, were
      compared within the two groups, and the calculated score of the complications in
      group 1 was 1.48 +/- 1.63, which was greater than that of group 2 (1.39 +/-
      1.64), but this difference did not reach statistical significance (P = 0.865).
      The 1-, 3-, and 5-year survival rates were 90.4, 76.2, and 71.4 % in group 1 and
      91.3, 73.9, and 69.6 % in group 2, respectively (P > 0.05). Seven patients (three
      in group 1 and four in group 2) had tumor recurrence after a median follow-up
      period of 72 months. The pathology findings were not different between the two
      groups. CONCLUSION: Recipients who meet the Milan or UCSF criteria after
      accepting successful preoperative downstaging therapy in LDLT can achieve the
      same result.

PMID- 22948845
TI  - Co-existence of chronic urticaria and metabolic syndrome: clinical implications.
AB  - A systemic pro-inflammatory and pro-coagulating state occurs in subjects who have
      both chronic urticaria and metabolic syndrome. To investigate the prevalence and
      clinical impact of metabolic syndrome in Korean patients with chronic urticaria,
      a hospital-based cross-sectional study of 131 patients was performed. Metabolic
      syndrome was assessed by the criteria of the National Cholesterol Education
      Program's Adult Treatment Panel III. Urticaria disease activity was assessed by
      total urticaria activity score (range 0-15). Thirty-nine patients (29.8%) had
      metabolic syndrome compared to 17.8% in a matched control group (p=0.001).
      Patients with chronic urticaria and metabolic syndrome were older, had a higher
      mean urticaria activity score and serum levels of eosinophil cationic protein,
      tumour necrosis factor-alpha, and complements, and showed a higher rate of
      negative autologous serum skin tests compared with those with-out metabolic
      syndrome. Logistic regression analysis indicated that an urticaria activity score
      of >= 13 (p=0.025) and the presence of metabolic syndrome (p=0.036) were
      independent predictors of uncontrolled chronic urticaria. We conclude that
      patients with severe and uncontrolled chronic urticaria should be evaluated for
      metabolic syndrome in order to reduce cardiovascular risk and improve chronic
      urticaria outcomes.

PMID- 22948846
TI  - Overcoming erlotinib resistance with tailored treatment regimen in patient
      derived xenografts from naive Asian NSCLC patients.
AB  - Overall benefits of EGFR-TKIs are limited because these treatments are largely
      only for adenocarcinoma (ADC) with EGFR activating mutation. The treatments also
      usually lead to development of resistances. We have established a panel of
      patient-derived xenografts (PDXs) from treatment naive Asian NSCLC patients,
      including those containing "classic" EGFR activating mutations. Some of these
      EGFR-mutated PDXs do not respond to erlotinib: LU1868 containing L858R/T790M
      mutations, and LU0858 having L858R mutation as well as c-MET gene amplification,
      both squamous cell carcinoma (SCC). Treatment of LU0858 with crizotinib, a small
      molecule inhibitor for ALK and c-MET, inhibited tumor growth and c-MET activity.
      Combination of erlotinib and crizotinib caused complete response, indicating the
      activation of both EGFR and c-MET promote its growth/survival. LU2503 and LU1901,
      both with wild-type EGFR and c-MET gene amplification, showed complete response
      to crizotinib alone, suggesting that c-MET gene amplification, not EGFR
      signaling, is the main oncogenic driver. Interestingly, LU1868 with the EGFR
      L858R/T790M, but without c-met amplification, had a complete response to
      cetuximab. Our data offer novel practical approaches to overcome the two most
      common resistances to EGFR-TKIs seen in the clinic using marketed target
      therapies.

PMID- 22948847
TI  - Voluntary limit setting and player choice in most intense online gamblers: an
      empirical study of gambling behaviour.
AB  - Social responsibility in gambling has become a major issue for the gaming
      industry. The possibility for online gamblers to set voluntary time and money
      limits are a social responsibility practice that is now widespread among online
      gaming operators. The main issue concerns whether the voluntary setting of such
      limits has any positive impact on subsequent gambling behaviour and whether such
      measures are of help to problem gamblers. In this paper, this issue is examined
      through data collected from a representative random sample of 100,000 players who
      gambled on the win2day gambling website. When opening an account at the win2day
      site, there is a mandatory requirement for all players to set time and cash-in
      limits (that cannot exceed 800 <euro> per week). During a 3-month period, all
      voluntary time and/or money limit setting behaviour by a subsample of online
      gamblers (n = 5,000) within this mandatory framework was tracked and recorded for
      subsequent data analysis. From the 5,000 gamblers, the 10 % most intense players
      (as measured by theoretical loss) were further investigated. Voluntary spending
      limits had the highest significant effect on subsequent monetary spending among
      casino and lottery gamblers. Monetary spending among poker players significantly
      decreased after setting a voluntary time limit. The highest significant decrease
      in playing duration was among poker players after setting a voluntary playing
      duration limit. The results of the study demonstrated that voluntary limit
      setting had a specific and significant effect on the studied gamblers. Therefore,
      voluntary limits appear to show an appropriate effect in the desired target group
      (i.e., the most gaming intense players).

PMID- 22948849
TI  - Assessment of substance abuse liability in rodents: self-administration, drug
      discrimination, and locomotor sensitization.
AB  - Assessing abuse liability is a crucial step in the development of a novel
      chemical entity (NCE) with central nervous system (CNS) activity or with chemical
      or pharmacological properties in common with known abused substances. Rodent
      assessment of abuse liability is highly attractive due to its relatively low cost
      and high predictive validity. Described in this unit are three rodent assays
      commonly used to provide data on the potential for abuse liability based on the
      acute effects of NCEs: specifically, self-administration, drug discrimination,
      and locomotor sensitization. As these assays provide insight into the potential
      abuse liability of NCEs as well as in vivo pharmacological mechanism(s) of
      action, they should form a key part of the development process for novel
      therapeutics aimed at treating CNS disorders.

PMID- 22948848
TI  - Overview of animal models of obesity.
AB  - The focus of this overview is on the animal models of obesity most commonly
      utilized in research. The models include monogenic models in the leptin pathway,
      polygenic diet-dependent models, and, in particular for their historical
      perspective, surgical and chemical models of obesity. However, there are far too
      many models to consider all of them comprehensively, especially those caused by
      selective molecular genetic approaches modifying one or more genes in specific
      populations of cells. Further, the generation and use of inducible transgenic
      animals (induced knock-out or knock-in) is not covered, even though they often
      carry significant advantages compared to traditional transgenic animals, e.g.,
      influences of the genetic modification during the development of the animals can
      be minimized. The number of these animal models is simply too large to be covered
      in this unit.

PMID- 22948850
TI  - Assessment of P-glycoprotein substrate and inhibition potential of test compounds
      in MDR1-transfected MDCK cells.
AB  - P-glycoprotein (P-gp) is the most widely studied drug transporter due to its
      potential role in drug disposition and efficacy, and drug-drug interactions
      (DDI). It is abundantly expressed in both the intestinal wall and blood-brain
      barrier where it serves as a drug permeability barrier while simultaneously
      facilitating drug elimination in the liver and kidney. It is also abundantly
      expressed in tumors where it can facilitate the elimination of chemotherapeutics,
      a phenomenon known as multidrug resistance (MDR). Clinically relevant DDIs
      involving P-gp are well documented; for example, the P-gp substrate, digoxin,
      exhibits toxicity when co-administered with a Pgp-inhibitor. This makes it
      essential to screen new chemical entities early in development for their
      potential to be a substrate and/or inhibitor of P-gp. Detailed in this unit is an
      in vitro protocol for assessing the P-gp substrate and inhibition potential of
      test compounds using the MDCK MDR1 and MDCK WT cell lines.

PMID- 22948851
TI  - Assessment of the time-dependent inhibition (TDI) potential of test compounds
      with human liver microsomes by IC50 shift method using a nondilution approach.
AB  - Time-dependent inhibition (TDI) of hepatic cytochrome P450 (CYP) enzymes is
      increasingly implicated in the majority of clinically relevant drug-drug
      interactions (DDIs). A time-dependent inhibitor or its reactive metabolite
      irreversibly inactivates CYP enzymes, thereby inhibiting the metabolism of other
      drugs. As the majority of marketed drugs are metabolized by CYP enzymes, their
      inhibition has important clinical consequences, such as in decreasing the
      metabolic clearance of a co-administered drug (victim drug). This could be life
      threatening, as such an effect narrows the therapeutic index for drugs such as
      warfarin and other potentially toxic agents. Therefore, it is essential to
      examine new chemical entities for their potential to cause TDI to minimize
      adverse drug reactions during human studies and use. This unit presents an in
      vitro procedure utilizing a nondilution method in human liver microsomes for
      determining the TDI potential of test compounds.

PMID- 22948852
TI  - Parallel chemistry in the 21st century.
AB  - The tool chest of techniques, methodologies, and equipment for conducting
      parallel chemistry is larger than ever before. Improvements in the laboratory and
      developments in computational chemistry have enabled compound library design at
      the desks of medicinal chemists. This unit includes a brief background in
      combinatorial/parallel synthesis chemistry, along with a discussion of evolving
      technologies for both solid- and solution-phase chemistry. In addition, there are
      discussions on designing compound libraries, acquisition/procurement of compounds
      and/or reagents, the chemistry and equipment used for chemical production,
      purification, sample handling, and data analysis.

PMID- 22948854
TI  - Magnetic polyoxometalates: from molecular magnetism to molecular spintronics and
      quantum computing.
AB  - In this review we discuss the relevance of polyoxometalate (POM) chemistry to
      provide model objects in molecular magnetism. We present several potential
      applications in nanomagnetism, in particular, in molecular spintronics and
      quantum computing.

PMID- 22948853
TI  - Should Y stay or should Y go: the evolution of non-recombining sex chromosomes.
AB  - Gradual degradation seems inevitable for non-recombining sex chromosomes. This
      has been supported by the observation of degenerated non-recombining sex
      chromosomes in a variety of species. The human Y chromosome has also degenerated
      significantly during its evolution, and theories have been advanced that the Y
      chromosome could disappear within the next ~5 million years, if the degeneration
      rate it has experienced continues. However, recent studies suggest that this is
      unlikely. Conservative evolutionary forces such as strong purifying selection and
      intrachromosomal repair through gene conversion balance the degeneration tendency
      of the Y chromosome and maintain its integrity after an initial period of faster
      degeneration. We discuss the evidence both for and against the extinction of the
      Y chromosome. We also discuss potential insights gained on the evolution of sex
      determining chromosomes by studying simpler sex-determining chromosomal regions
      of unicellular and multicellular microorganisms.

PMID- 22948855
TI  - Diagnostic accuracy of fine-needle aspiration cytology of the breast in Japan:
      report from the Working Group on the Accuracy of Breast Fine-Needle Aspiration
      Cytology of the Japanese Society of Clinical Cytology.
AB  - The Working Group of the Japanese Society of Clinical Cytology was assembled to
      assess the current status of breast cytology in Japan by conducting a large-scale
      survey regarding the accuracy of fine-needle aspiration biopsy (FNAB) in Japan.
      We collected data and investigated the status of breast cytological diagnosis at
      12 different cooperating facilities in Japan, and re-evaluated their false
      negative and false-positive cases. Among 30,535 individuals who underwent a
      breast cytological examination, analyses were conducted on 10,890 individuals
      (35.7%) in whom cytological diagnoses were confirmed by histology. Among these
      patients, the cytological diagnosis had an inadequate rate of 17.7%, an
      indeterminate rate of 7.8%, a positive predictive value of 'malignancy suspected'
      cells of 92.4%, an absolute sensitivity of 76.7%, a complete sensitivity of
      96.7%, a specificity of 84.3%, a positive predictive value of 'malignant' cells
      of 99.5%, a false-negative value of 3.31%, a false-positive value of 0.25% and an
      accuracy rate of 88.0%. Subsequently, 297 false-negative and 23 false-positive
      cases were re-evaluated and several factors were characterized (i.e. histological
      type, tumor size and misread points). This survey collected data from a large
      number of cases for breast FNAB. Based on our survey, the accuracy of FNAB in
      Japan was relatively high compared with the goal of assessment of diagnostic
      accuracy. However, there were some false-negative and false-positive cases.
      Improvements in accuracy resulting from the learning points in the present study
      will lead to more useful and reliable diagnostic tools in clinical practice.

PMID- 22948856
TI  - Pharmacokinetic and tolerability profile of pridopidine in healthy-volunteer poor
      and extensive CYP2D6 metabolizers, following single and multiple dosing.
AB  - Pridopidine is being developed for the treatment of impaired motor function
      associated with Huntington's disease and belongs to a new class of compounds
      known as dopidines, which act as dopaminergic stabilizers. In vitro studies have
      shown that pridopidine is a substrate for the P450 cytochrome 2D6 enzyme
      (CYP2D6), and clinical data show that the half-life of pridopidine is different
      following single dosing versus at steady state. To further investigate the
      pharmacokinetic profile of pridopidine and to establish whether dose adjustment
      is needed in poor CYP2D6 metabolizers, a single-centre, open-label, multiple-dose
      study in healthy volunteers was performed. In total, 24 extensive CYP2D6
      metabolizers (EMs) and 12 poor CYP2D6 metabolizers (PMs) were enrolled. Both
      groups received 45 mg pridopidine twice daily (b.i.d.). Plasma samples were taken
      during the first day of b.i.d. dosing (Day 1) and at steady state, following 14
      days of b.i.d. dosing. At Day 1, total exposure in PMs was almost three times
      higher than those in EMs (AUC0-infinity = 11,192 and 3,782 h.ng/mL, respectively;
      PM/EM ratio = 2.96; p < 0.001). However, at steady state, PMs and EMs had
      comparable exposure due to a reduction in pridopidine elimination in EMs over
      time. Thus, at steady-state peak (C max) and total (AUC0-24) exposures were only
      1.24 and 1.29 times higher, respectively, in PMs than EMs. These results support
      that pridopidine is a CYP2D6 auto-inhibitor. Pridopidine was well tolerated in
      both EMs and PMs. The slightly higher exposure level in PMs at steady state does
      not indicate a need for dose adjustment or genotyping for CYP2D6 metabolizer
      status.

PMID- 22948857
TI  - The basic role of basic science.

PMID- 22948858
TI  - Taking the middle path in evaluating technology in medical education.

PMID- 22948860
TI  - Correlation between bithermal caloric test results and vestibular evoked myogenic
      potentials (VEMPs) in normal subjects.
AB  - Bithermal caloric testing and vestibular evoked myogenic potentials (VEMPs) are
      both diagnostic tools for the study of the vestibular system. The first tests the
      horizontal semicircular canal and the second evaluates the saccule and lower
      vestibular nerve. The results of these two tests can therefore be expected to be
      correlated. The aim of this study was to compare bithermal caloric test results
      with VEMP records in normal subjects to verify whether they are correlated.
      MATERIAL AND METHOD: A prospective study was conducted in 60 healthy subjects (30
      men and 30 women) who underwent otoscopy, pure tone audiometry, bithermal caloric
      testing and VEMPs. From the caloric test, we assessed the presence of possible
      vestibular hypofunction, whether there was directional preponderance and
      reflectivity of each ear (all based on both slow phase velocity and nystagmus
      frequency). The analysed VEMPs variables were: p1 and n1 latency, corrected
      amplitude, interaural p1 latency difference and p1 interaural amplitude
      asymmetry. We compared the reflectivity, hypofunction and directional
      preponderance of the caloric tests with the corrected amplitudes and amplitude
      asymmetries of the VEMPs. No correlations were found in the different comparisons
      between bithermal caloric testing results and VEMPs except for a weak correlation
      (p = 0.039) when comparing preponderance based on the number of nystagmus in the
      caloric test and amplitude asymmetry with 99 dB tone burst in the VEMPs test. The
      results indicate that the two diagnostic tests are not comparable, so one of them
      cannot replace the other, but the use of both increases diagnostic success in
      some conditions.

PMID- 22948859
TI  - Large-scale MHC class II genotyping of a wild lemur population by next generation
      sequencing.
AB  - The critical role of major histocompatibility complex (MHC) genes in disease
      resistance, along with their putative function in sexual selection, reproduction
      and chemical ecology, make them an important genetic system in evolutionary
      ecology. Studying selective pressures acting on MHC genes in the wild
      nevertheless requires population-wide genotyping, which has long been challenging
      because of their extensive polymorphism. Here, we report on large-scale
      genotyping of the MHC class II loci of the grey mouse lemur (Microcebus murinus)
      from a wild population in western Madagascar. The second exons from MHC-DRB and 
      DQB of 772 and 672 individuals were sequenced, respectively, using a 454
      sequencing platform, generating more than 800,000 reads. Sequence analysis,
      through a stepwise variant validation procedure, allowed reliable typing of more
      than 600 individuals. The quality of our genotyping was evaluated through three
      independent methods, namely genotyping the same individuals by both cloning and
      454 sequencing, running duplicates, and comparing parent-offspring dyads; each
      displaying very high accuracy. A total of 61 (including 20 new) and 60 (including
      53 new) alleles were detected at DRB and DQB genes, respectively. Both loci were
      non-duplicated, in tight linkage disequilibrium and in Hardy-Weinberg
      equilibrium, despite the fact that sequence analysis revealed clear evidence of
      historical selection. Our results highlight the potential of 454 sequencing
      technology in attempts to investigate patterns of selection shaping MHC variation
      in contemporary populations. The power of this approach will nevertheless be
      conditional upon strict quality control of the genotyping data.

PMID- 22948861
TI  - The normal uncinate process: histology and clinical relevance.
AB  - In this three-center, prospective, non-randomized, controlled trial, we performed
      a qualitative and quantitative histological and morphometric assessment of the
      normal uncinate process (UP). The soft tissue and bony elements of the normal UP
      of 16 adults were investigated and compared with 28 age- and gender-matched
      archival reference-group samples of neighboring structures of the inferior and
      middle turbinates. A series of measurements were taken and included the thickness
      of the mucosal layers and bone, epithelial height, basement membrane thickness,
      number of lamina propria inflammatory cells, and the area fraction (AF) of the
      epithelium, connective tissue, glands, veins and arteries. The data showed that
      the medial and lateral mucosal layers are built of loose connective tissue and
      harbor various inflammatory cell population, abundant glands, and thin-walled
      small-caliber venules. In-between, there is a thin lamellar compact bone (<= 80
      MUm) or a significantly thicker cancellous bone (110-400 MUm; P < 0.001). Both
      mucosal layers are similar in thickness, epithelial height, basement membrane
      thickness, and AF of soft-tissue constituents. A comparison with the lateral
      aspect of the inferior and middle turbinates showed that the AF of the connective
      tissue, total submucosal glands, submucosal serous and mucous glands, and veins
      of the lateral mucosa are significantly different (all P < 0.001). This diversity
      may point to different physiological roles for the UP and the inferior and middle
      turbinates. The UP rich glandular network, which is probably responsible for
      drainage and ventilation of the maxillary sinus into the ethmoid infundibulum
      laterally and the frontal sinus into the middle meatus medially, supports the
      argument that it is preferable, particularly for the less complicated cases, to
      keep the normal physiology of the ethmoid infundibulum and use bone- and mucosa
      sparing techniques for the management of refractory chronic sinus disease.

PMID- 22948862
TI  - Predictors of surgical approaches for the repair of anterior cranial base
      encephaloceles.
AB  - Surgical approaches to the anterior cranial base have changed considerably with
      the introduction of endonasal endoscopic surgery. This study aims to define the
      factors which help in selecting the optimal surgical approach for the treatment
      of anterior cranial base encephaloceles. Patients who received treatment for
      anterior cranial base encephaloceles at our department between 1996 and 2011 were
      included in the study. Patients' charts were reviewed retrospectively to collect
      the necessary data. Treatment periods were classified as before 2000, between
      2000 and 2005, and after 2005. The relationship between the treatment period,
      localization of encephalocele, symptoms related with the lesion, size of skull
      base defect, and selected treatment modality were investigated. Twenty-five
      patients, aged between 1 and 61 years with anterior encephaloceles were included
      in the study. Patients with small asymptomatic frontonasal and trans-ethmoidal
      encephaloceles (n = 5) were followed without surgery. An external approach with
      or without subfrontal craniotomy was mainly preferred for resection of sincipital
      encephaloceles (n = 10), especially with facial deformity. A subfrontal
      craniotomy approach was used for resection of basal encephaloceles in two cases
      before 2000. Two cases with sincipital encephaloceles and six cases with basal
      encephaloceles underwent pure endonasal endoscopic surgery after 2000. Cranial
      base defects of every size could be repaired using the endoscopic approach.
      Hydrocephalus and meningitis were the two complications seen after craniotomy in
      a follow-up period of 13-26 (mean 14.5) months. An external approach with or
      without craniotomy is needed for encephaloceles with external mass and facial
      deformity. Otherwise, sincipital and basal encephaloceles can be repaired
      successfully using the endonasal endoscopic approach.

PMID- 22948863
TI  - Surface tethered epidermal growth factor protects proliferating and
      differentiating multipotential stromal cells from FasL-induced apoptosis.
AB  - Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed
      as aids in regenerating bone and adipose tissues, as these cells form osteoblasts
      and adipocytes. A major obstacle to this use of MSC is the initial loss of cells
      postimplantation. This cell death in part is due to ubiquitous nonspecific
      inflammatory cytokines such as FasL generated in the implant site. Our group
      previously found that soluble epidermal growth factor (sEGF) promotes MSC
      expansion. Furthermore, tethering EGF (tEGF) onto a two-dimensional surface
      altered MSC responses, by restricting epidermal growth factor receptor (EGFR) to
      the cell surface, causing sustained activation of EGFR, and promoting survival
      from FasL-induced death. sEGF by causing internalization of EGFR does not support
      MSC survival. However, for tEGF to be useful in bone regeneration, it needs to
      allow for MSC differentiation into osteoblasts while also protecting emerging
      osteoblasts from apoptosis. tEGF did not block induced differentiation of MSCs
      into osteoblasts, or adipocytes, a common default MSC-differentiation pathway.
      MSC-derived preosteoblasts showed increased Fas levels and became more
      susceptible to FasL-induced death, which tEGF prevented. Differentiating
      adipocytes underwent a reduction in Fas expression and became resistant to FasL
      induced death, with tEGF having no further survival effect. tEGF protected
      undifferentiated MSC from combined insults of FasL, serum deprivation, and
      physiologic hypoxia. Additionally, tEGF was dominant in the face of sEGF to
      protect MSC from FasL-induced death. Our results suggest that MSCs and
      differentiating osteoblasts need protective signals to survive in the
      inflammatory wound milieu and that tEGF can serve this function.

PMID- 22948864
TI  - Contribution of selected gene mutations to resistance in clinical isolates of
      vancomycin-intermediate Staphylococcus aureus.
AB  - Infections with vancomycin-intermediate Staphylococcus aureus (VISA) have been
      associated with vancomycin treatment failures and poor clinical outcomes. Routine
      identification of clinical isolates with increased vancomycin MICs remains
      challenging, and no molecular marker exists to aid in diagnosis of VISA strains.
      We tested vancomycin susceptibilities by using microscan, Etest, and population
      analyses in a collection of putative VISA, methicillin-resistant S. aureus, and
      methicillin-sensitive S. aureus (VSSA) infectious isolates from community- or
      hospital-associated S. aureus infections (n = 77) and identified 22 VISA and 9
      heterogeneous VISA (hVISA) isolates. Sequencing of VISA candidate loci vraS,
      vraR, yvqF, graR, graS, walR, walK, and rpoB revealed a high diversity of
      nonsynonymous single-nucleotide polymorphisms (SNPs). For vraS, vraR, yvqF, walK,
      and rpoB, SNPs were more frequently present in VISA and hVISA than in VSSA
      isolates, whereas mutations in graR, graS, and walR were exclusively detected in
      VISA isolates. For each of the individual loci, SNPs were only detected in about
      half of the VISA isolates. All but one VISA isolate had at least one SNP in any
      of the genes sequenced, and isolates with an MIC of 6 or 8 MUg/ml harbored at
      least 2 SNPs. Overall, increasing vancomycin MICs were paralleled by a higher
      proportion of isolates with SNPs. Depending on the clonal background, SNPs
      appeared to preferentially accumulate in vraS and vraR for sequence type 8 (ST8)
      and in walK and walR for ST5 isolates. Taken together, by comparing VISA, hVISA,
      and VSSA controls, we observed preferential clustering of SNPs in VISA candidate
      genes, with an unexpectedly high diversity across these loci. Our results support
      a polygenetic etiology of VISA.

PMID- 22948865
TI  - Regulation of RamA by RamR in Salmonella enterica serovar Typhimurium: isolation
      of a RamR superrepressor.
AB  - RamA is a transcription factor involved in regulating multidrug resistance in
      Salmonella enterica serovar Typhimurium SL1344. Green fluorescent protein (GFP)
      reporter fusions were exploited to investigate the regulation of RamA expression
      by RamR. We show that RamR represses the ramA promoter by binding to a
      palindromic sequence and describe a superrepressor RamR mutant that binds to the
      ramA promoter sequence more efficiently, thus exhibiting a ramA inactivated
      phenotype.

PMID- 22948866
TI  - Use of xylitol to enhance the therapeutic efficacy of polymethylmethacrylate
      based antibiotic therapy in treatment of chronic osteomyelitis.
AB  - Using a rabbit model of postsurgical osteomyelitis, we demonstrate that
      incorporation of xylitol into polymethylmethacrylate (PMMA) bone cement enhances
      the elution of daptomycin under in vivo conditions. We also demonstrate that this
      can be correlated with an improved therapeutic outcome in the treatment of a
      chronic bone infection following surgical debridement.

PMID- 22948867
TI  - Effect of maraviroc on HIV disease progression-related biomarkers.
AB  - The potential effect of blocking the CCR5 receptor on HIV disease progression
      biomarkers is not well understood. We showed that an 8-day maraviroc (MVC)
      monotherapy clinical test (MCT) can be used in selecting patients to receive MVC
      containing combined antiretroviral therapy (cART). Using this MCT model, we
      assessed the effect of MVC on several HIV disease progression biomarkers during
      the MCT (MVC-specific effect) and following short-term (12-week) cART. We
      compared 45 patients on MVC monotherapy with a control group of 25 patients on
      MVC-sparing cART. We found that MVC did not modify any biomarkers in patients
      that had no virological response after the MCT. MVC-specific effects in patients
      with virological responses included increased CD8(+) T-cell activation and
      senescence levels, preservation of an increase in soluble CD14 (sCD14), and a
      decrease in D dimer levels. After 12 weeks, MVC-containing cART increased CD8(+)
      T-cell counts and preserved CD4(+) T-cell senescence levels compared with MVC
      sparing cART. Moreover, there was a decrease in sCD14 levels in patients that
      received MVC-containing cART. In conclusion, effects compatible with CD8(+) T
      cell redistribution in peripheral blood were observed after MVC therapy. However,
      MVC was associated with a favorable profile in HIV disease progression biomarkers
      only in patients with a virological response. These results support a potential
      clinical benefit of a therapy which includes MVC in HIV-infected patients.

PMID- 22948868
TI  - Prevention and treatment of virulent bacterial biofilms with an enzymatic nitric
      oxide-releasing dressing.
AB  - The use of percutaneous medical devices often results in nosocomial infections.
      Attachment of microorganisms to the surfaces of these medical devices triggers
      biofilm formation, which presents significant complications to the health of a
      patient and may lead to septicemia, thromboembolism, or endocarditis if not
      correctly treated. Although several antimicrobials are commonly used for
      prevention of biofilm formation, they have limited efficacy against formed
      biofilms. In this study, we report the use of an enzymatic, gaseous nitric oxide
      (gNO)-releasing dressing for the prevention and treatment of Acinetobacter
      baumannii, methicillin-resistant Staphylococcus aureus, and Pseudomonas
      aeruginosa biofilms. Results show that the bactericidal activity against biofilms
      of the test strains was dependent on time and rate of gNO release from the
      dressing. Following 6 h of treatment, gNO-releasing dressings significantly
      inhibited the growth of test strains relative to vehicle control dressings,
      demonstrating eradication of bacterial concentrations of up to 10(5) CFU/cm(2).
      Complete cell death was observed for both prevention of biofilm formation and
      treatment of 24-h-grown biofilms after 6 h of treatment with the gNO-releasing
      dressings. Further, gNO-releasing dressings were more efficient against formed
      biofilms than other antimicrobial agents currently used. These results
      demonstrate that the gNO-releasing dressing can produce sufficient levels of gNO
      over a therapeutically relevant duration for maximal bactericidal effects against
      virulent bacterial strains known to cause nosocomial infections.

PMID- 22948869
TI  - Comparison of fluconazole renal penetration levels in healthy and Candida
      albicans-infected Wistar rats.
AB  - The aims of this study were to evaluate free levels of fluconazole (FCZ) in the
      kidneys of healthy and Candida albicans-infected Wistar rats using microdialysis
      and to establish the relationship between free renal and total plasma levels
      under both conditions. Microdialysis recovery rates were determined in vitro by
      dialysis, and retrodialysis recovery rates were determined in vivo by
      retrodialysis. The recovery rate was around 50%, independent of the method, drug
      concentration, or condition (in vitro or in vivo) used. FCZ kidney penetration in
      healthy and infected rats was investigated after the administration of 10 mg/kg
      of body weight intravenously (i.v.) or 50 mg/kg orally (n = 6/group) and blood
      and microdialysate sample harvesting at predetermined time points up to 24 and 18
      h, respectively. There were no statistical differences between the area under the
      free concentration-time curve (AUC(0-infinity)) values in plasma and in tissue
      for either healthy or infected groups for the same dose regimen investigated. The
      antifungal tissue penetrations were similar for both doses and under all
      conditions investigated (ranging from 0.77 to 0.84). The unbound fraction of FCZ
      was concentration independent (86.0% +/- 2.0%), allowing the prediction of free
      renal levels using pharmacokinetic parameters obtained from total plasma fitting.
      The results showed that free renal and free plasma levels are similar in healthy
      and systemically C. albicans-infected rats. Therefore, free plasma levels are a
      good surrogate to estimate free FCZ renal concentrations in systemic candidiasis
      and can be used to optimize dosing regimens for this drug.

PMID- 22948870
TI  - Optimizing Echinocandin dosing and susceptibility breakpoint determination via in
      vivo pharmacodynamic evaluation against Candida glabrata with and without fks
      mutations.
AB  - Echinocandins are a preferred therapy for invasive candidiasis due to their
      potency and broad spectrum. Resistance, especially in Candida glabrata, is an
      emerging threat to their use. Pharmacodynamic (PD) studies examining reduced
      susceptibility secondary to fks mutations in C. glabrata are lacking. The current
      study explored PD targets for anidulafungin, caspofungin, and micafungin in an in
      vivo invasive candidiasis model against 11 C. glabrata isolates with known or
      putative fks mutations. The PD targets were compared to those of 8 wild-type (WT)
      isolates. The MIC ranges in the WT group were 0.03 to 0.25 mg/liter for
      anidulafungin, 0.03 to 0.25 mg/liter for caspofungin, and 0.01 to 0.06 mg/liter
      for micafungin. The MIC ranges for mutants were 0.06 to 4, 0.25 to 16, and 0.13
      to 8 mg/liter for the same compounds, respectively. The mean free drug 24-h area
      under the concentration-time curve (AUCf)/MIC ratio associated with a stasis
      endpoint for the WT group was 13.2 for anidulafungin, 2.04 for caspofungin, and
      6.78 for micafungin. Comparative values for mutants were 3.43, 2.67, and 0.90,
      respectively. Pharmacokinetic data from patients suggest that the C. glabrata PD
      targets needed for success in this model could be achieved based on MIC values of
      0.25 mg/liter for anidulafungin, 2 mg/liter for caspofungin, and 0.5 mg/liter for
      micafungin. These values are higher than recently identified epidemiology cutoff
      values (ECVs). The results suggest that drug-specific MIC breakpoints could be
      increased for caspofungin and micafungin against C. glabrata and could include
      organisms with mutations in fks-1 and fks-2. While identification of genetic
      mutants is epidemiologically important, the phenotype (MIC) provides a better
      predictor of therapeutic efficacy.

PMID- 22948871
TI  - Targeting the substrate preference of a type I nitroreductase to develop
      antitrypanosomal quinone-based prodrugs.
AB  - Nitroheterocyclic prodrugs are used to treat infections caused by Trypanosoma
      cruzi and Trypanosoma brucei. A key component in selectivity involves a specific
      activation step mediated by a protein homologous with type I nitroreductases,
      enzymes found predominantly in prokaryotes. Using data from determinations based
      on flavin cofactor, oxygen-insensitive activity, substrate range, and inhibition
      profiles, we demonstrate that NTRs from T. cruzi and T. brucei display many
      characteristics of their bacterial counterparts. Intriguingly, both enzymes
      preferentially use NADH and quinones as the electron donor and acceptor,
      respectively, suggesting that they may function as NADH:ubiquinone
      oxidoreductases in the parasite mitochondrion. We exploited this preference to
      determine the trypanocidal activity of a library of aziridinyl benzoquinones
      against bloodstream-form T. brucei. Biochemical screens using recombinant NTR
      demonstrated that several quinones were effective substrates for the parasite
      enzyme, having K(cat)/K(m) values 2 orders of magnitude greater than those of
      nifurtimox and benznidazole. In tests against T. brucei, antiparasitic activity
      mirrored the biochemical data, with the most potent compounds generally being
      preferred enzyme substrates. Trypanocidal activity was shown to be NTR dependent,
      as parasites with elevated levels of this enzyme were hypersensitive to the
      aziridinyl agent. By unraveling the biochemical characteristics exhibited by the
      trypanosomal NTRs, we have shown that quinone-based compounds represent a class
      of trypanocidal compound.

PMID- 22948872
TI  - High-throughput sequencing reveals the incomplete, short-term recovery of infant
      gut microbiota following parenteral antibiotic treatment with ampicillin and
      gentamicin.
AB  - The infant gut microbiota undergoes dramatic changes during the first 2 years of
      life. The acquisition and development of this population can be influenced by
      numerous factors, and antibiotic treatment has been suggested as one of the most
      significant. Despite this, however, there have been relatively few studies which
      have investigated the short-term recovery of the infant gut microbiota following
      antibiotic treatment. The aim of this study was to use high-throughput sequencing
      (employing both 16S rRNA and rpoB-specific primers) and quantitative PCR to
      compare the gut microbiota of nine infants who underwent parenteral antibiotic
      treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks
      after the conclusion of treatment, relative to that of nine matched healthy
      controls. The investigation revealed that the gut microbiota of the antibiotic
      treated infants had significantly higher proportions of Proteobacteria (P =
      0.0049) and significantly lower proportions of Actinobacteria (P = 0.00001) (and
      the associated genus Bifidobacterium [P = 0.0132]) as well as the genus
      Lactobacillus (P = 0.0182) than the untreated controls 4 weeks after the
      cessation of treatment. By week 8, the Proteobacteria levels remained
      significantly higher in the treated infants (P = 0.0049), but the Actinobacteria,
      Bifidobacterium, and Lactobacillus levels had recovered and were similar to those
      in the control samples. Despite this recovery of total Bifidobacterium numbers,
      rpoB-targeted pyrosequencing revealed that the number of different
      Bifidobacterium species present in the antibiotic-treated infants was reduced. It
      is thus apparent that the combined use of ampicillin and gentamicin in early life
      can have significant effects on the evolution of the infant gut microbiota, the
      long-term health implications of which remain unknown.

PMID- 22948873
TI  - Cosubstrate tolerance of the aminoglycoside resistance enzyme Eis from
      Mycobacterium tuberculosis.
AB  - We previously demonstrated that aminoglycoside acetyltransferases (AACs) display
      expanded cosubstrate promiscuity. The enhanced intracellular survival (Eis)
      protein of Mycobacterium tuberculosis is responsible for the resistance of this
      pathogen to kanamycin A in a large fraction of clinical isolates. Recently, we
      discovered that Eis is a unique AAC capable of acetylating multiple amine groups
      on a large pool of aminoglycoside (AG) antibiotics, an unprecedented property
      among AAC enzymes. Here, we report a detailed study of the acyl-coenzyme A (CoA)
      cosubstrate profile of Eis. We show that, in contrast to other AACs, Eis
      efficiently uses only 3 out of 15 tested acyl-CoA derivatives to modify a variety
      of AGs. We establish that for almost all acyl-CoAs, the number of sites acylated
      by Eis is smaller than the number of sites acetylated. We demonstrate that the
      order of n-propionylation of the AG neamine by Eis is the same as the order of
      its acetylation. We also show that the 6' position is the first to be n
      propionylated on amikacin and netilmicin. By sequential acylation reactions, we
      show that AGs can be acetylated after the maximum possible n-propionylation of
      their scaffolds by Eis. The information reported herein will advance our
      understanding of the multiacetylation mechanism of inactivation of AGs by Eis,
      which is responsible for M. tuberculosis resistance to some AGs.

PMID- 22948874
TI  - Immunocytochemistry for vancomycin using a monoclonal antibody that reveals
      accumulation of the drug in rat kidney and liver.
AB  - We prepared monoclonal antibodies against N-(gamma
      maleimidobutyryloxy)succinimide-conjugated vancomycin (VM). The monoclonal
      antibody was specific for conjugated or free VM. The monoclonal antibody enabled
      us to develop an immunocytochemical method for detecting the uptake of VM in the
      rat kidney and liver. Three hours after a single intravenous (i.v.) injection of
      VM at the therapeutic dose, the immunocytochemistry revealed that VM accumulated
      in large amounts in both the S1 and S2 segments and in much smaller amounts in
      the S3 segment of the proximal tubules as well as in the distal tubules and
      collecting ducts. The drug was detected in the cytoplasm, cytoplasmic irregular
      granules, nuclei, and microvilli of the proximal tubule cells. The distal tubules
      and collecting ducts contained scattered swollen cells in which both the nuclei
      and cytoplasm were heavily immunostained. Twenty-four hours after injection, most
      of the swollen cells returned back to normal size and had somewhat decreased
      immunostaining. Also, significant amounts of VM remained accumulated for as long
      as 8 days postadministration. In the liver, similar drug accumulation was
      observed in the Kupffer cells and the endothelial cells of the hepatic sinusoids
      but not in the hepatocytes, suggesting that vancomycin cannot be eliminated via
      the liver. Immunoelectron microscopic studies demonstrated that in the collecting
      ducts, uptake of VM occurred exclusively in the lysosomes and cytoplasm of the
      principal cells and scarcely in the intercalated cells. Furthermore, double
      fluorescence staining using rats simultaneously administered with VM and
      gentamicin strongly suggests that both drugs colocalized in lysosomes in the
      proximal tubule cells of kidneys.

PMID- 22948875
TI  - No recurrence of Pneumocystis jirovecii Pneumonia after solid organ
      transplantation regardless of secondary prophylaxis.
AB  - There are no data on the efficacy of secondary prophylaxis against Pneumocystis
      pneumonia after solid organ transplantation. Therefore, we investigated the rate
      of recurrence of Pneumocystis pneumonia after solid organ transplantation in a
      retrospective cohort study. Between 2005 and 2011, a total of 41 recipients
      recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary
      prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis
      pneumonia during the follow-up, regardless of secondary prophylaxis.

PMID- 22948876
TI  - In vitro activities of nine antifungal drugs against 81 Phialophora and
      Cyphellophora isolates.
AB  - Cyphellophora guyanensis (n = 15), other Cyphellophora species (n = 11),
      Phialophora europaea (n = 43), and other Phialophora species (n = 12) were tested
      in vitro against nine antifungal drugs. The MIC(90)s across all of the strains (n
      = 81) were, in increasing order, as follows: posaconazole, 0.063 MUg/ml;
      itraconazole, 0.5 MUg/ml; voriconazole, 1 MUg/ml; micafungin, 1 MUg/ml;
      terbinafine, 2 MUg/ml; isavuconazole, 4 MUg/ml; caspofungin, 4 MUg/ml;
      fluconazole, 8 MUg/ml; amphotericin B, 16 MUg/ml.

PMID- 22948877
TI  - Cryptococcus neoformans-Cryptococcus gattii species complex: an international
      study of wild-type susceptibility endpoint distributions and epidemiological
      cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole.
AB  - Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus
      gattii species complex versus fluconazole, itraconazole, posaconazole, and
      voriconazole are not available. We established ECVs for these species and agents
      based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs
      for C. neoformans (including isolates of molecular type VNI [MICs for 759 to
      1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705
      to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV
      isolates) were gathered in 15 to 24 laboratories (Europe, United States,
      Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and
      were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI
      yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans
      were evaluated. CLSI RPMI medium ECVs for distributions originating from at least
      three laboratories, which included >=95% of the modeled WT population, were as
      follows: fluconazole, 8 MUg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII),
      16 MUg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 MUg/ml (VGII);
      itraconazole, 0.25 MUg/ml (VNI), 0.5 MUg/ml (C. neoformans and C. gattii nontyped
      and VGI to VGIII), and 1 MUg/ml (VGIV); posaconazole, 0.25 MUg/ml (C. neoformans
      nontyped and VNI) and 0.5 MUg/ml (C. gattii nontyped and VGI); and voriconazole,
      0.12 MUg/ml (VNIV), 0.25 MUg/ml (C. neoformans and C. gattii nontyped, VNI,
      VNIII, VGII, and VGIIa,), and 0.5 MUg/ml (VGI). The number of laboratories
      contributing data for other molecular types was too low to ascertain that the
      differences were due to factors other than assay variation. In the absence of
      clinical breakpoints, our ECVs may aid in the detection of isolates with acquired
      resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI
      M27-S3 documents.

PMID- 22948879
TI  - Structure-activity relationships among the kanamycin aminoglycosides: role of
      ring I hydroxyl and amino groups.
AB  - The kanamycins form an important subgroup of the 4,6-disubstituted 2
      deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B,
      tobramycin, and dibekacin. These compounds interfere with protein synthesis by
      targeting the ribosomal decoding A site, and they differ in the numbers and
      locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We
      synthesized kanamycin analogues characterized by subtle variations of the 2' and
      6' substituents of ring I. The functional activities of the kanamycins and the
      synthesized analogues were investigated (i) in cell-free translation assays on
      wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii)
      in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte
      translation assays to determine activity on eukaryotic ribosomes. Position 2'
      forms an intramolecular H bond with O5 of ring II, helping the relative
      orientations of the two rings with respect to each other. This bond becomes
      critical for drug activity when a 6'-OH substituent is present.

PMID- 22948878
TI  - Mode of action, in vitro activity, and in vivo efficacy of AFN-1252, a selective
      antistaphylococcal FabI inhibitor.
AB  - The mechanism of action of AFN-1252, a selective inhibitor of Staphylococcus
      aureus enoyl-acyl carrier protein reductase (FabI), which is involved in fatty
      acid biosynthesis, was confirmed by using biochemistry, macromolecular synthesis,
      genetics, and cocrystallization of an AFN-1252-FabI complex. AFN-1252
      demonstrated a low propensity for spontaneous resistance development and a time
      dependent reduction of the viability of both methicillin-susceptible and
      methicillin-resistant S. aureus, achieving a >=2-log(10) reduction in S. aureus
      counts over 24 h, and was extremely potent against clinical isolates of S. aureus
      (MIC(90), 0.015 MUg/ml) and coagulase-negative staphylococci (MIC(90), 0.12
      MUg/ml), regardless of their drug resistance, hospital- or community-associated
      origin, or other clinical subgroup. AFN-1252 was orally available in mouse
      pharmacokinetic studies, and a single oral dose of 1 mg/kg AFN-1252 was
      efficacious in a mouse model of septicemia, providing 100% protection from an
      otherwise lethal peritoneal infection of S. aureus Smith. A median effective dose
      of 0.15 mg/kg indicated that AFN-1252 was 12 to 24 times more potent than
      linezolid in the model. These studies, demonstrating a selective mode of action,
      potent in vitro activity, and in vivo efficacy, support the continued
      investigation of AFN-1252 as a targeted therapeutic for staphylococcal
      infections.

PMID- 22948880
TI  - Inhibitors of reactive oxygen species accumulation delay and/or reduce the
      lethality of several antistaphylococcal agents.
AB  - Perturbation of hydroxyl radical accumulation by subinhibitory concentrations of
      2,2'-bipyridyl plus thiourea protects Escherichia coli from being killed by 3
      lethal antimicrobial classes. Here, we show that 2,2'-bipyridyl plus thiourea
      delays and/or reduces antimicrobial killing of Staphylococcus aureus by
      daptomycin, moxifloxacin, and oxacillin. While the protective effect of 2,2'
      bipyridyl plus thiourea varied among strains and compounds, the data support the
      hypothesis that hydroxyl radical enhances antimicrobial lethality.

PMID- 22948881
TI  - Preclinical experiments on the release behavior of biodegradable nanofibrous
      multipharmaceutical membranes in a model of four-wall intrabony defect.
AB  - Guided tissue regeneration (GTR) therapy has been widely used to regenerate lost
      periodontium from periodontal disease. However, in terms of regenerative
      periodontal therapy, a multidrug-loaded biodegradable carrier can be even more
      promising in dealing with periodontal disease. In the current study, we
      fabricated biodegradable nanofibrous collagen membranes that were loaded with
      amoxicillin, metronidazole, and lidocaine by an electrospinning technique. The in
      vitro release behavior and the cytotoxicity of the membranes were investigated. A
      four-wall intrabony defect was created in rabbits for in vivo release analysis.
      The bioactivity of the released antibiotics was also examined. The experimental
      results showed that the drug-loaded collagen membranes could provide sustainable
      release of effective amoxicillin, metronidazole, and lidocaine for 28, 56, and 8
      days, respectively, in vivo. Furthermore, the bioactivity of the released
      antibiotics remained high, with average bioactivities of 50.5% for amoxicillin
      against Staphylococcus aureus and 58.6% for metronidazole against Escherichia
      coli. The biodegradable nanofibrous multipharmaceutical membranes developed in
      this study may provide a promising solution for regenerative periodontal therapy.

PMID- 22948882
TI  - T-2307 causes collapse of mitochondrial membrane potential in yeast.
AB  - T-2307, an arylamidine compound, has been previously reported to have broad
      spectrum in vitro and in vivo antifungal activities against clinically
      significant pathogens, including Candida species, Cryptococcus neoformans, and
      Aspergillus species, and is now undergoing clinical trials. Here we investigated
      the mechanism of action of T-2307 using yeast cells and mitochondria isolated
      from yeast and rat liver. Nonfermentative growth of Candida albicans and
      Saccharomyces cerevisiae in glycerol medium, in which yeasts relied on
      mitochondrial respiratory function, was inhibited at 0.001 to 0.002 MUg/ml (0.002
      to 0.004 MUM) of T-2307. However, fermentative growth in dextrose medium was not
      inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a
      cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the
      mitochondrial function of C. albicans and S. cerevisiae at concentrations near
      the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential
      in mitochondria isolated from S. cerevisiae at 20 MUM. On the other hand, in
      isolated rat liver mitochondria, T-2307 did not have any effect on the
      mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory
      and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In
      conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was
      also demonstrated that the fungal mitochondrion is an attractive antifungal
      target.

PMID- 22948884
TI  - Red man syndrome adverse reaction following intravenous infusion of cefepime.
AB  - We report the first case of cefepime-induced "red-man syndrome," which appeared
      30 min following drug infusion and was confirmed with a rechallenge test. This
      syndrome is classically associated with vancomycin infusion and is the result of
      non-IgE mediated mast cell degranulation. While this adverse effect can be easily
      managed with drug withdrawal and antihistamine administration, it is unknown
      whether it can be prevented with slower cefepime infusion and preinfusion
      antihistamines, as is the case with vancomycin.

PMID- 22948883
TI  - Identification of hepatitis C virus inhibitors targeting different aspects of
      infection using a cell-based assay.
AB  - With 2 to 3% of the worldwide population chronically infected, hepatitis C virus
      (HCV) infection continues to be a major health care burden. Unfortunately,
      current interferon-based treatment options are not effective in all patients and
      are associated with significant side effects. Consequently, there is an ongoing
      need to identify and develop new anti-HCV therapies. Toward this goal, we
      previously developed a cell-based HCV infection assay for antiviral compound
      screening based on a low-multiplicity-of-infection approach that uniquely allows
      for the identification of antiviral compounds that target cell culture-derived
      HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we
      report the screening of the NCI Diversity Set II library, containing 1,974
      synthesized chemical compounds, and the identification of compounds with specific
      anti-HCV activity. In combination with toxicity counterscreening, we identified
      30 hits from the compound library, 13 of which showed reproducible and dose
      dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic
      concentration [CC(50)]/50% effective concentration [EC(50)]) of greater than 6.
      Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as
      infectious HCVcc-based assembly and secretion analysis, we determined that
      different compounds within this group of candidate inhibitors target different
      steps of viral infection. The compounds identified not only will serve as
      biological probes to study and further dissect the biology of viral infection but
      also should facilitate the development of new anti-HCV therapeutic treatments.

PMID- 22948885
TI  - Genotypic and phenotypic evaluation of the evolution of high-level daptomycin
      nonsusceptibility in vancomycin-resistant Enterococcus faecium.
AB  - Whole-genome sequencing and cell membrane studies of three clonal Enterococcus
      faecium strains with daptomycin MICs of 4, 32, and 192 MUg/ml were performed,
      revealing nonsynonymous single nucleotide variants in eight open reading frames,
      including those predicted to encode a phosphoenolpyruvate-dependent, mannose
      specific phosphotransferase system, cardiolipin synthetase, and EzrA. Membrane
      studies revealed a higher net surface charge among the daptomycin-nonsusceptible
      isolates and increased septum formation in the isolate with a daptomycin MIC of
      192 MUg/ml.

PMID- 22948887
TI  - Isolated hypomagnesemia in a patient treated with capecitabine.
AB  - Hypomagnesemia is known to occur for a variety of renal, gastrointestinal and
      other causes, and is often associated with other electrolyte and metabolic
      disturbances. We present a case of isolated hypomagnesemia in a patient who had
      been treated with the chemotherapy agent capecitabine. The approach to diagnosis
      and treatment is discussed. We postulate that capecitabine may cause isolated
      hypomagnesemia, possibly due to renal magnesium loss. 

PMID- 22948886
TI  - Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid
      leukemia from 1999 and 2009: analysis of a national cohort of patients in the
      Pediatric Health Information Systems database.
AB  - BACKGROUND: Acute lymphoblastic (ALL) and myeloid leukemia (AML) account for
      approximately 26% of pediatric cancers. Anthracyclines are widely used to treat
      these leukemias, but dosing is limited by cardiotoxicity. Data support the
      efficacy of dexrazoxane as a cardioprotectant in children; however, dexrazoxane
      use in children is not universally accepted due to concerns about toxicity,
      impact on the antitumor effect of anthracyclines, and risk of secondary malignant
      neoplasms (SMN). PROCEDURE: We conducted a retrospective cohort study to describe
      patterns of dexrazoxane use in pediatric patients with ALL or AML using the
      Pediatric Health Information Systems (PHIS) database. Patients identified as
      having de novo ALL and AML at these PHIS hospitals were included. RESULTS: Of
      8,733 patients with ALL and 2,556 with AML, 207 (2.4%) and 52 (2.0%) received
      dexrazoxane, respectively. Dexrazoxane use was greater in older children with ALL
      and AML and in black patients and males with ALL. Dexrazoxane use varied across
      time and by region in ALL, but not in AML. Prescribing practices differed across
      institutions and most patients received the first dose early or late after the
      start of leukemia treatment. CONCLUSIONS: Dexrazoxane administration is limited
      in patients with ALL and AML and prescribing practices vary across the country.
      Further work is necessary to understand how dexrazoxane is used in patients at
      highest risk of developing cardiotoxicity and to define its true effect on the
      development of SMNs.

PMID- 22948888
TI  - Emergency neurological life support: acute ischemic stroke.
AB  - Acute ischemic stroke is a neurological emergency that can be treated with time
      sensitive interventions, including intravenous thrombolysis and endovascular
      approaches. Extensive study has demonstrated that rapid assessment and treatment
      are essential to improving neurological outcome. For this reason, acute ischemic
      stroke was chosen as an Emergency Neurological Life Support protocol. The
      protocol focuses on the first hour following the onset of neurological deficit.

PMID- 22948890
TI  - Advancing the science of medicines regulation: the role of the 21st-century
      medicines regulator.
AB  - The history of medicines regulation is punctuated with sudden swings in focus
      mandated by a public injured by medicines and skeptical of regulators' abilities
      to protect them. As stakeholder communities and the science that undergirds
      medicines have both grown more sophisticated, seemingly conflicting mission
      equities, such as public health protection vs. promotion or population vs.
      individual patient product development focus, have created new challenges to
      defining the mission and role of twenty-first-century medicines regulators. The
      role of medicines regulators as a nationally focused, retrospective assessor of
      data is rapidly shifting to that of a prospective generator of public data and
      tools to help drive what has now become a global product development and
      regulatory enterprise that is fast gaining recognition as an integral part of any
      truly effective twenty-first-century health-care system. This article discusses
      this evolution and describes how regulatory science will help to both drive and
      define it.

PMID- 22948889
TI  - Pharmacogenomics and individualized medicine: translating science into practice.
AB  - Research on genes and medications has advanced our understanding of the genetic
      basis of individual drug responses. The aim of pharmacogenomics is to develop
      strategies for individualizing therapy for patients, in order to optimize outcome
      through knowledge of the variability of the human genome and its influence on
      drug response. Pharmacogenomics research is translational in nature and ranges
      from discovery of genotype-phenotype relationships to clinical trials that can
      provide proof of clinical impact. Advances in pharmacogenomics offer significant
      potential for subsequent clinical application in individual patients; however,
      the translation of pharmacogenomics research findings into clinical practice has
      been slow. Key components to successful clinical implementation of
      pharmacogenomics will include consistent interpretation of pharmacogenomics test
      results, availability of clinical guidelines for prescribing on the basis of test
      results, and knowledge-based decision support systems.

PMID- 22948891
TI  - Individualization of drug therapy: history, present state, and opportunities for
      the future.
AB  - Individualization of drug therapy, described as tailoring drug selection and drug
      dosing to a given patient, has been an objective of physicians and other health
      care providers for centuries. An understanding of the pathogenesis of the
      disease, the mechanism of action of the drug, and exposure-response relationships
      provides the framework for individualization. There are many approaches to
      individualization: selecting an antibiotic based on minimum effective
      concentrations and bacterial sensitivity, population (sparse sample)
      pharmacokinetics, therapeutic drug monitoring and, more recently,
      pharmacogenomics. The goal of individualization is to optimize the efficacy of a
      drug, minimize its toxicity, or both. With the growth of technology and
      databases, drug-disease-trial models and simulation have become useful for
      integrating information from many different domains. Physiology-based
      pharmacokinetic (PBPK) models have provided a mechanistic approach to
      individualization, and clinical trial designs such as those involving enrichment
      have also enabled individualization. In the future, "-omics" technologies,
      vaccines, ex vivo gene therapy, and the so-called "diseases-in-a-dish" will
      provide additional strategies to achieve individualization.

PMID- 22948892
TI  - Influence of environmental and genetic factors on CYP1A2 activity in individuals
      of South Asian and European ancestry.
AB  - The drug-metabolizing enzyme CYP1A2 contributes to the metabolism of a number of
      commonly used medicines and displays wide interindividual variability. The aim of
      this study was to investigate CYP1A2 activity in a population of South Asian
      ancestry and compare it with a population of European ancestry. CYP1A2 activity
      was determined using the 4 h paraxanthine/caffeine saliva concentration ratio
      following a 100-mg oral dose of caffeine in healthy individuals of South Asian (n
      = 166) and European (n = 166) ancestry. Participants were surveyed for extrinsic
      ethnic factors and genotyped for polymorphisms in CYP1A2 and related genes.
      Significantly lower CYP1A2 activity was observed in South Asian participants
      (median: 0.42; range: 0.10-1.06) as compared with European participants (0.54;
      0.12-1.64) (P < 0.01). Multiple linear regression indicated that 41% of the
      variability in CYP1A2 activity could be explained by the diet, lifestyle, and
      genetic factors studied.

PMID- 22948893
TI  - Personalizing antiplatelet therapy with clopidogrel.
AB  - Dual antiplatelet therapy with aspirin and clopidogrel is the accepted standard
      for prevention of ischemic complications after percutaneous coronary intervention
      and has been shown to reduce cardiovascular events in patients with acute
      coronary syndromes (ACSs). There is substantial interindividual variability in
      antiplatelet response to clopidogrel. Various clinical studies have demonstrated
      that patients with high on-clopidogrel platelet reactivity incur an increased
      risk for ischemic events. In recent years, several clinical and demographic
      variables as well as multiple genetic factors contributing to the variability in
      antiplatelet response to clopidogrel have been identified. We discuss strategies
      based on platelet function testing or genotyping for improvement of antiplatelet
      effects of clopidogrel and thereby clinical outcome.

PMID- 22948895
TI  - Polymorphisms in endothelial nitric oxide synthase (eNOS) and vascular
      endothelial growth factor (VEGF) predict sunitinib-induced hypertension.
AB  - Hypertension is an important side effect of sunitinib treatment. In a
      retrospective study in 255 patients, single-nucleotide polymorphisms (SNPs) in
      vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor
      receptor (VEGFR)-2, endothelin-1 (ET-1), and endothelium-derived nitric oxide
      synthase (eNOS) were multivariately tested against hypertension grades and
      changes in systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial
      BP (MAP). Next, the association between hypertension and survival in patients
      with metastatic renal cell cancer (mRCC) was studied. Greater elevations in SBP
      and MAP were associated with the presence of a haplotype in VEGFA (P = 0.014 and
      P = 0.036, respectively). The tendency to develop grade 3 hypertension was
      associated with this haplotype and also with a SNP in eNOS (P = 0.031 and P =
      0.045, respectively). In mRCC patients, sunitinib-induced hypertension was found
      to confer a survival benefit, with the mean overall survival being prolonged by
      7.2 months (P = 0.035 and P = 0.026 for SBP and DBP elevations, respectively).
      Genetic polymorphisms in VEGFA and eNOS independently predict rise in BP and/or
      development of severe hypertension in sunitinib-treated patients. Grade 3
      hypertension was found to be an independent factor for overall survival in
      patients with mRCC.

PMID- 22948896
TI  - Interpreting pharmacogenetic data in the developing neonate: the challenge of
      hitting a moving target.
AB  - In a 2010 review in Clinical Pharmacology & Therapeutics, Nick Holford noted that
      in neonates and young infants, maturation of the organs responsible for drug
      clearance is a more important determinant of pharmacokinetics (PK) than is body
      size.(1) Here we review recent developments that provide new insights into how
      physiological and environmental changes associated with adaptation to
      extrauterine life affect the ontogeny of drug biotransformation and
      interpretation of genotype-phenotype relationships in newborns and infants.

PMID- 22948894
TI  - A perspective on efflux transport proteins in the liver.
AB  - Detailed knowledge regarding the influence of hepatic transport proteins on drug
      disposition has advanced at a rapid pace over the past decade. Efflux transport
      proteins located in the basolateral and apical (canalicular) membranes of
      hepatocytes play an important role in the hepatic elimination of many endogenous
      and exogenous compounds, including drugs and metabolites. This review focuses on
      the role of these efflux transporters in hepatic drug excretion. The impact of
      these proteins as underlying factors for disease is highlighted, and the
      importance of hepatic efflux proteins in the efficacy and toxicity of drugs is
      discussed. In addition, a brief overview of methodology to evaluate the function
      of hepatic efflux transport proteins is provided. Current challenges in
      predicting the impact of altered efflux protein function on systemic, intestinal,
      and hepatocyte exposure to drugs and metabolites are highlighted.

PMID- 22948897
TI  - The effect of safinamide, a novel drug for Parkinson's disease, on pressor
      response to oral tyramine: a randomized, double-blind, clinical trial.
AB  - This randomized, double-blind, placebo-, comparator (selegiline 10 mg/day)-, and
      positive (phenelzine 30 mg/day)-controlled study investigated the pressor
      response to oral tyramine under fasting conditions after the administration of
      safinamide at therapeutic (100 mg/day) and supratherapeutic (350 mg/day) dosing
      regimens in healthy volunteers for the purpose of assessing the need for dietary
      restrictions. Pressor response was characterized by Tyr30, defined as the
      tyramine dose that triggers a sustained increase in systolic blood pressure (SBP)
      of >=30 mm Hg as compared with baseline SBP. The primary end point was the
      tyramine sensitivity factor (TSF), defined as the ratio of Tyr30 at screening to
      Tyr30 under treatment. Safinamide induced a mild increase in TSF; however, the
      effect at each of the doses was numerically lower than those of the comparators
      (geometric mean TSFs: placebo, 1.52; safinamide 100 mg, 2.15; safinamide 350 mg,
      2.74; selegiline, 3.12; phenelzine, 9.98). This study confirms that safinamide is
      a highly selective monoamine oxidase-B inhibitor, even at supratherapeutic doses,
      and suggests that it can be administered without tyramine-related dietary
      restrictions.

PMID- 22948899
TI  - Feasibility of real time next generation sequencing of cancer genes linked to
      drug response: results from a clinical trial.
AB  - The successes of targeted drugs with companion predictive biomarkers and the
      technological advances in gene sequencing have generated enthusiasm for
      evaluating personalized cancer medicine strategies using genomic profiling. We
      assessed the feasibility of incorporating real-time analysis of somatic mutations
      within exons of 19 genes into patient management. Blood, tumor biopsy and
      archived tumor samples were collected from 50 patients recruited from four cancer
      centers. Samples were analyzed using three technologies: targeted exon sequencing
      using Pacific Biosciences PacBio RS, multiplex somatic mutation genotyping using
      Sequenom MassARRAY and Sanger sequencing. An expert panel reviewed results prior
      to reporting to clinicians. A clinical laboratory verified actionable mutations.
      Fifty patients were recruited. Nineteen actionable mutations were identified in
      16 (32%) patients. Across technologies, results were in agreement in 100% of
      biopsy specimens and 95% of archival specimens. Profiling results from paired
      archival/biopsy specimens were concordant in 30/34 (88%) patients. We
      demonstrated that the use of next generation sequencing for real-time genomic
      profiling in advanced cancer patients is feasible. Additionally, actionable
      mutations identified in this study were relatively stable between archival and
      biopsy samples, implying that cancer mutations that are good predictors of drug
      response may remain constant across clinical stages.

PMID- 22948898
TI  - Adaptation to a spouse's disability by parents of adult children with mental
      illness or developmental disability.
AB  - OBJECTIVE: This study examined the effects on well-being of a spouse's disability
      among aging parents already serving as caregivers of adult children with severe
      mental illness or a developmental disability. METHODS: The study sample consisted
      of two groups of participants in the Wisconsin Longitudinal Study of 1957 high
      school graduates and their randomly selected siblings-those who had a child with
      a disability (N=227) and a matched comparison group of parents who did not have a
      child with a disability (N=1,463). The participants were surveyed in 1992-1994
      and 2004-2006, and participants with a spouse with a disability in 1992-1994 were
      excluded from the analysis. The effect of multiple caregiving roles was
      investigated by using regression analysis. RESULTS: Parents of adult children
      with severe mental illness were more likely than either parents of adult children
      with developmental disabilities or the comparison group to report that their
      spouse developed a disability in the early retirement years. The experience of
      caring for a spouse with a disability and the experience of caring for an adult
      child with disabilities had additive effects in eroding the well-being of older
      adults. Parents of adult children with severe mental illness in general had the
      lowest levels of well-being. CONCLUSIONS: As they move into their retirement
      years, aging parents who care for children with long-term disabilities are likely
      to experience multiple caregiving responsibilities. Service providers must
      address the needs of these aging parents and develop interventions to help them
      cope and plan for their future.

PMID- 22948900
TI  - The promise and challenges of stem cell-based therapies for skeletal diseases:
      stem cell applications in skeletal medicine: potential, cell sources and
      characteristics, and challenges of clinical translation.
AB  - Despite decades of research, remaining safety concerns regarding disease
      transmission, heterotopic tissue formation, and tumorigenicity have kept stem
      cell-based therapies largely outside the standard-of-care for musculoskeletal
      medicine. Recent insights into trophic and immune regulatory activities of
      mesenchymal stem cells (MSCs), although incomplete, have stimulated a plethora of
      new clinical trials for indications far beyond simply supplying progenitors to
      replenish or re-build lost/damaged tissues. Cell banks are being established and
      cell-based products are in active clinical trials. Moreover, significant advances
      have also been made in the field of pluripotent stem cells, in particular the
      recent development of induced pluripotent stem cells. Their indefinite
      proliferation potential promises to overcome the limited supply of tissue
      specific cells and adult stem cells. However, substantial hurdles related to
      their safety must be overcome for these cells to be clinically applicable.

PMID- 22948901
TI  - Supercharging with trivalent metal ions in native mass spectrometry.
AB  - Addition of 1.0 mM LaCl(3) to aqueous ammonium acetate solutions containing
      proteins in their folded native forms can result in a significant increase in the
      molecular ion charging obtained with electrospray ionization as a result of
      cation adduction. In combination with m-nitrobenzyl alcohol, molecular ion charge
      states that are greater than the number of basic sites in the protein can be
      produced from these native solutions, even for lysozyme, which is
      conformationally constrained by four intramolecular disulfide bonds. Circular
      dichroism spectroscopy indicates that the conformation of ubiquitin is not
      measurably affected with up to 1.0 M LaCl(3), but ion mobility data indicate that
      the high charge states that are formed when 1.0 mM LaCl(3) is present are more
      unfolded than the low charge states formed without this reagent. These and other
      results indicate that the increased charging is a result of La(3+) preferentially
      adducting onto compact or more native-like conformers during ESI and the gas
      phase ions subsequently unfolding as a result of increased Coulomb repulsion.
      Electron capture dissociation of these high charge-state ions formed from these
      native solutions results in comparable sequence coverage to that obtained for
      ions formed from denaturing solutions without supercharging reagents, making this
      method a potentially powerful tool for obtaining structural information in native
      mass spectrometry.

PMID- 22948902
TI  - Ligand migration in the gaseous insulin-CB7 complex--a cautionary tale about the
      use of ECD-MS for ligand binding site determination.
AB  - Knowledge of the structure of protein-ligand complexes can aid in understanding
      their roles within complex biological processes. Here we use electrospray
      ionization (ESI) coupled to a Fourier transform ion cyclotron resonance mass
      spectrometer to investigate the noncovalent binding of the macrocycle
      cucurbit[7]uril (CB7) to bovine insulin. Recent condensed-phase experiments
      (Chinai et al., J. Am. Chem. Soc. 133:8810-8813, 2011) indicate that CB7 binds
      selectively to the N-terminal phenylalanine of the insulin B-chain. Competition
      experiments employing ESI mass spectrometry to assess complex formation between
      CB7 and wild type insulin B-chain vs. a mutant B-chain, confirm that the N
      terminal phenylalanine plays in important role in solution-phase binding.
      However, analysis of fragment ions produced by electron capture dissociation
      (ECD) of CB7 complexed to intact insulin and to the insulin B-chain suggests a
      different picture. The apparent gas-phase binding site, as identified by the ECD,
      lies further along the insulin B-chain. Together, these studies thus indicate
      that the CB7 ligand migrates in the ESI mass spectrometry analysis. Migration is
      likely aided by the presence of additional interactions between CB7 and the
      insulin B-chain, which are not observed in the crystal structure. While this
      conformational difference may result simply from the removal of solvent and
      addition of excess protons by the ESI, we propose that the migration may be
      enhanced by charge reduction during the ECD process itself because ion-dipole
      interactions are key to CB7 binding. The results of this study caution against
      using ECD-MS as a stand-alone structural probe for the determination of solution
      phase binding sites.

PMID- 22948903
TI  - Chemometric data analysis for deconvolution of overlapped ion mobility profiles.
AB  - We present the details of a data analysis approach for deconvolution of the ion
      mobility (IM) overlapped or unresolved species. This approach takes advantage of
      the ion fragmentation variations as a function of the IM arrival time. The data
      analysis involves the use of an in-house developed data preprocessing platform
      for the conversion of the original post-IM/collision-induced dissociation mass
      spectrometry (post-IM/CID MS) data to a Matlab compatible format for chemometric
      analysis. We show that principle component analysis (PCA) can be used to examine
      the post-IM/CID MS profiles for the presence of mobility-overlapped species.
      Subsequently, using an interactive self-modeling mixture analysis technique, we
      show how to calculate the total IM spectrum (TIMS) and CID mass spectrum for each
      component of the IM overlapped mixtures. Moreover, we show that PCA and IM
      deconvolution techniques provide complementary results to evaluate the validity
      of the calculated TIMS profiles. We use two binary mixtures with overlapping IM
      profiles, including (1) a mixture of two non-isobaric peptides (neurotensin
      (RRPYIL) and a hexapeptide (WHWLQL)), and (2) an isobaric sugar isomer mixture of
      raffinose and maltotriose, to demonstrate the applicability of the IM
      deconvolution.

PMID- 22948904
TI  - Silver triflate-catalyzed tandem reaction of N'-(2-alkynylbenzylidene)hydrazide
      with pyridyne.
AB  - A silver triflate-catalyzed tandem reaction of N'-(2-alkynylbenzylidene)hydrazide
      with pyridyne is presented. Different outcomes are obtained, depending on the
      pyridynes utilized in the transformation.

PMID- 22948905
TI  - Association between estrogen receptor-beta dinucleotide repeat polymorphism and
      incidence of femoral fracture.
AB  - Estrogens are thought to play an important role in bone metabolism through
      estrogen receptors (ER). Dinucleotide (cytosine-adenine, CA) repeat polymorphism
      in the human ER-beta gene (ESR2) has been reported to be associated with bone
      mineral density. We aimed to further elucidate the importance of this
      polymorphism in the pathogenesis of osteoporosis by examining its association
      with the incidence of femoral fracture. Deoxyribonucleic acids extracted from the
      renal cortex of 1489 consecutive Japanese autopsies (799 male, mean age 79 years,
      690 female, mean age 82 years) with complete clinical/pathological data were
      enrolled in the study. ESR2 CA repeat polymorphism was determined by polymerase
      chain reaction using fluorescein-labeled primers. The presence or absence of
      femoral fracture during each subject's lifetime was determined by thorough
      examination of the clinical record. Incidence of femoral fracture in subjects
      bearing at least one allele of 20 CA repeats (4/132, 3.0 %) was significantly
      lower than in those without this allele (127/1357, 9.4 %, P = 0.0098). After
      adjustments for age and sex, logistic regression analysis revealed that having no
      allele of 20 CA repeats was an independent risk factor of femoral fracture
      [adjusted odds ratio (OR) 3.875, 95 % confidence interval (CI) 1.392-10.788, P =
      0.0095], which was emphasized among women (adjusted OR 6.360, 95 % CI 1.520
      26.618, P = 0.0133). Japanese subjects, especially women, bearing at least one
      allele of 20 CA repeats in the ESR2 may have a lower risk of femoral fracture
      than those without it, suggesting this polymorphism plays a role in bone
      metabolism.

PMID- 22948906
TI  - Clearance efficacy of autoantibodies in double filtration plasmapheresis for
      pemphigus foliaceus.

PMID- 22948907
TI  - Structural features of the single-stranded DNA-binding protein MoSub1 from
      Magnaporthe oryzae.
AB  - The well studied general transcription cofactor Sub1/PC4 has multiple functions
      in transcription. It plays both a negative and a positive role in transcription
      initiation and is involved in elongation and downstream transcription processes
      and as a transcription reinitiation factor. MoSub1, a Sub1/PC4 orthologue from
      rice blast fungus, binds the single-stranded DNA dT(12) tightly with an affinity
      of 186 nM. The crystal structure of MoSub1 has been solved to 1.79 A resolution.
      The structure of the protein shows high similiarity to the structure of PC4 and
      it has a similar dimer interface and DNA-binding region to PC4, indicating that
      MoSub1 could bind DNA using the same motif as other proteins of the Sub1/PC4
      family. There are two novel features in the MoSub1 structure: a region N-terminal
      to the DNA-binding domain and a C-terminal extension. The region N-terminal to
      the DNA-binding domain of MoSub1 turns back towards the DNA-binding site and may
      interact directly with DNA or the DNA-binding site. The C-terminal extension
      region, which is absent in PC4, may not be capable of interacting with DNA and is
      one possible reason for the differences between Sub1 and PC4.

PMID- 22948908
TI  - On the variability of experimental data in macromolecular crystallography.
AB  - Experimental errors as determined by data-processing algorithms in macromolecular
      crystallography are compared with the direct error estimates obtained by a
      multiple crystal data-collection protocol. It is found that several-fold error
      inflation is necessary to account for crystal-to-crystal variation. It is shown
      that similar error inflation is observed for data collected from multiple
      sections of the same crystal, indicating non-uniform crystal growth as one of the
      likely sources of additional data variation. Other potential sources of error
      inflation include differential X-ray absorption for different reflections and
      variation of unit-cell parameters. The underestimation of the experimental errors
      is more severe in lower resolution shells and for reflections characterized by a
      higher signal-to-noise ratio. These observations partially account for the gap
      between the expected and the observed R values in macromolecular crystallography.

PMID- 22948909
TI  - Structural basis for bathochromic shift of fluorescence in far-red fluorescent
      proteins eqFP650 and eqFP670.
AB  - The crystal structures of the far-red fluorescent proteins (FPs) eqFP650
      (lambda(ex)(max)/lambda(em)(max) 592/650 nm) and eqFP670
      (lambda(ex)(max)/lambda(em)(max) 605/670 nm), the successors of the far-red FP
      Katushka (lambda(ex)(max)/lambda(em)(max) 588/635 nm), have been determined at
      1.8 and 1.6 A resolution, respectively. An examination of the structures
      demonstrated that there are two groups of changes responsible for the
      bathochromic shift of excitation/emission bands of these proteins relative to
      their predecessor. The first group of changes resulted in an increase of
      hydrophilicity at the acylimine site of the chromophore due to the presence of
      one and three water molecules in eqFP650 and eqFP670, respectively. These water
      molecules provide connection of the chromophore with the protein scaffold via
      hydrogen bonds causing an ~15 nm bathochromic shift of the eqFP650 and eqFP670
      emission bands. The second group of changes observed in eqFP670 arises from
      substitution of both Ser143 and Ser158 by asparagines. Asn143 and Asn158 of
      eqFP670 are hydrogen bonded with each other, as well as with the protein scaffold
      and with the p-hydroxyphenyl group of the chromophore, resulting in an additional
      ~20 nm bathochromic shift of the eqFP670 emission band as compared to eqFP650.
      The role of the observed structural changes was verified by mutagenesis.

PMID- 22948910
TI  - Structural and functional studies of ReP1-NCXSQ, a protein regulating the squid
      nerve Na+/Ca2+ exchanger.
AB  - The protein ReP1-NCXSQ was isolated from the cytosol of squid nerves and has been
      shown to be required for MgATP stimulation of the squid nerve Na(+)/Ca(2+)
      exchanger NCXSQ1. In order to determine its mode of action and the corresponding
      biologically active ligand, sequence analysis, crystal structures and mass
      spectrometric studies of this protein and its Tyr128Phe mutant are reported.
      Sequence analysis suggests that it belongs to the CRABP family in the FABP
      superfamily. The X-ray structure at 1.28 A resolution shows the FABP beta-barrel
      fold, with a fatty acid inside the barrel that makes a relatively short hydrogen
      bond to Tyr128 and shows a double bond between C9 and C10 but that is disordered
      beyond C12. Mass-spectrometric studies identified this fatty acid as palmitoleic
      acid, confirming the double bond between C9 and C10 and establishing a length of
      16 C atoms in the aliphatic chain. This acid was caught inside during the culture
      in Escherichia coli and therefore is not necessarily linked to the biological
      activity. The Tyr128Phe mutant was unable to activate the Na(+)/Ca(2+) exchanger
      and the corresponding crystal structure showed that without the hydrogen bond to
      Tyr128 the palmitoleic acid inside the barrel becomes disordered. Native mass
      spectrometric analysis confirmed a lower occupancy of the fatty acid in the
      Tyr128Phe mutant. The correlation between (i) the lack of activity of the
      Tyr128Phe mutant, (ii) the lower occupancy/disorder of the bound palmitoleic acid
      and (iii) the mass-spectrometric studies of ReP1-NCXSQ suggests that the
      transport of a fatty acid is involved in regulation of the NCXSQ1 exchanger,
      providing a novel insight into the mechanism of its regulation. In order to
      identify the biologically active ligand, additional high-resolution mass
      spectrometric studies of the ligands bound to ReP1-NCXSQ were performed after
      incubation with squid nerve vesicles both with and without MgATP. These studies
      clearly identified palmitic acid as the fatty acid involved in regulation of the
      Na(+)/Ca(2+) exchanger from squid nerve.

PMID- 22948912
TI  - Detection of alternative conformations by unrestrained refinement.
AB  - Unrestrained refinement is stable for the vast majority of atoms when working at
      atomic resolution. Nevertheless, geometrical restraints should be retained in
      refinement for residues that are present in several (alternative) conformations
      in the crystal used for the X-ray experiment; otherwise, such residues
      deteriorate significantly. The authors believe that a large distortion of a
      residue in unrestrained refinement may hint at the presence of alternative
      conformations of this residue. To obtain these hints in a routine way, two
      methods of analyzing the shifts of atomic centres resulting from several cycles
      of unrestrained refinement are described. A simple diagram plotting the values of
      the atomic shifts against the residue number may give an idea of the
      crystallographic order of different parts of the structure at a qualitative
      level. To put the analysis on a more quantitative basis, several decision-making
      procedures were developed and tested which compose a list of residues that are
      likely to be present in alternative conformations or to be disordered and so
      should be checked thoroughly using Fourier syntheses and included in the model
      with alternative conformations when necessary. The parameters and performance of
      the suggested procedures were estimated by the use of 203 PDB structures refined
      at resolutions better than 1.2 A. Decision-making procedures based on analysis of
      atomic shifts were found to be more reliable than similar procedures based on
      atomic displacement parameters or density values calculated at atomic centres.

PMID- 22948911
TI  - Spatial distribution of radiation damage to crystalline proteins at 25-300 K.
AB  - The spatial distribution of radiation damage (assayed by increases in atomic B
      factors) to thaumatin and urease crystals at temperatures ranging from 25 to 300
      K is reported. The nature of the damage changes dramatically at approximately 180
      K. Above this temperature the role of solvent diffusion is apparent in thaumatin
      crystals, as solvent-exposed turns and loops are especially sensitive. In urease,
      a flap covering the active site is the most sensitive part of the molecule and
      nearby loops show enhanced sensitivity. Below 180 K sensitivity is correlated
      with poor local packing, especially in thaumatin. At all temperatures, the
      component of the damage that is spatially uniform within the unit cell accounts
      for more than half of the total increase in the atomic B factors and correlates
      with changes in mosaicity. This component may arise from lattice-level, rather
      than local, disorder. The effects of primary structure on radiation sensitivity
      are small compared with those of tertiary structure, local packing, solvent
      accessibility and crystal contacts.

PMID- 22948913
TI  - The structure of augmenter of liver regeneration crystallized in the presence of
      50 mM CdCl2 reveals a novel Cd2Cl4O6 cluster that aids in crystal packing.
AB  - The crystal structure of the protein augmenter of liver regeneration containing a
      14-residue hexahistidine purification tag (hsALR) has been determined to 2.4 A
      resolution by Cd-SAD using a highly redundant data set collected on a rotating
      anode home X-ray source and processed in 1998. The hsALR crystal structure is a
      tetramer composed of two homodimers bridged by a novel Cd(2)Cl(4)O(6) cluster via
      binding to the side-chain carboxylate groups of two solvent-exposed aspartic acid
      residues. A comparison with the native sALR tetramer shows that the cluster
      dramatically changes the hsALR dimer-dimer interface, which can now better
      accommodate the extra 14 N-terminal residues associated with the purification
      tag. The refined 2.4 A resolution structure is in good agreement with both the X
      ray data (R(cryst) of 0.165, R(free) of 0.211) and the expected stereochemistry
      (r.m.s. deviations from ideality for bond lengths and bond angles of 0.007 A and
      1.15 degrees , respectively).

PMID- 22948914
TI  - Structure of Escherichia coli BamB and its interaction with POTRA domains of
      BamA.
AB  - In Escherichia coli, the BAM complex is essential for the assembly and insertion
      of outer membrane proteins (OMPs). The BAM complex is comprised of an integral
      beta-barrel outer membrane protein BamA and four accessory lipoproteins BamB,
      BamC, BamD and BamE. Here, the crystal structure of BamB is reported. The crystal
      of BamB diffracted to 2.0 A with one monomer in the asymmetric unit and the
      structure is composed of eight-bladed beta-propeller motifs. Pull-down and
      Western blotting assays indicate that BamB interacts directly with the POTRA 1-3
      domain of BamA and the C-terminal region of the POTRA 1-3 domain plays an
      important role in the interaction, while the POTRA 1-2 domain is not required for
      the interaction.

PMID- 22948915
TI  - High-resolution structure of Bombyx mori lipoprotein 7: crystallographic
      determination of the identity of the protein and its potential role in
      detoxification.
AB  - Three crystal structures of a lipoprotein (Bmlp7) of unknown function, a member
      of the 30 kDa lipoprotein family from mulberry silkworm (Bombyx mori L.)
      haemolymph, have been determined. The 1.33 A resolution structure is an excellent
      example of how a precise crystallographic study can contribute to protein
      identification. The correct sequence of this haemolymph-isolated protein was
      assigned thanks to superb-quality electron-density maps. Two unexpected cadmium
      cations were found in this crystal structure [Bmlp7-I(Cd)] and their presence may
      be connected to a detoxification mechanism in this insect. For a comparison of
      the metal-binding sites, the crystal structure of a platinum complex (Bmlp7-Pt)
      was also solved at 1.94 A resolution. The third (2.50 A resolution) structure, of
      the native protein harvested in a different season (Bmlp7-II), corresponds to a
      different polymorph with an altered pattern of intermolecular interactions and
      with a total absence of cadmium ions and highlights the possible involvement of
      Bmlp7 in the response to environmental pollution. The N-terminal domain of Bmlp7
      has a fold resembling a clockwise spiral created by six helices and can be
      classified as a VHS domain. The C-terminal domain is folded as a beta-trefoil.
      The biological function of Bmlp7 is unknown, but its structural homology to sugar
      binding proteins suggests that, in analogy to other 30 kDa haemolymph
      lipoproteins, it could play a role as an anti-apoptotic factor or function in the
      immune response of the insect to fungal infections.

PMID- 22948916
TI  - Segmenting data sets for RIP.
AB  - Specific radiation damage can be used for the phasing of macromolecular crystal
      structures. In practice, however, the optimization of the X-ray dose used to
      'burn' the crystal to induce specific damage can be difficult. Here, a method is
      presented in which a single large data set that has not been optimized in any way
      for radiation-damage-induced phasing (RIP) is segmented into multiple sub-data
      sets, which can then be used for RIP. The efficacy of this method is demonstrated
      using two model systems and two test systems. A method to improve the success of
      this type of phasing experiment by varying the composition of the two sub-data
      sets with respect to their separation by image number, and hence by absorbed
      dose, as well as their individual completeness is illustrated.

PMID- 22948917
TI  - Structure of a tetrameric galectin from Cinachyrella sp. (ball sponge).
AB  - The galectins are a family of proteins that bind with highest affinity to N
      acetyllactosamine disaccharides, which are common constituents of asparagine
      linked complex glycans. They play important and diverse physiological roles,
      particularly in the immune system, and are thought to be critical metastatic
      agents for many types of cancer cells, including gliomas. A recent bioactivity
      based screen of marine sponge (Cinachyrella sp.) extract identified an ancestral
      member of the galectin family based on its unexpected ability to positively
      modulate mammalian ionotropic glutamate receptor function. To gain insight into
      the mechanistic basis of this activity, the 2.1 A resolution X-ray structure of
      one member of the family, galectin CchG-1, is reported. While the protomer
      exhibited structural similarity to mammalian prototype galectin, CchG-1 adopts a
      novel tetrameric arrangement in which a rigid toroidal-shaped 'donut' is
      stabilized in part by the packing of pairs of vicinal disulfide bonds. Twofold
      symmetry between binding-site pairs provides a basis for a model for interaction
      with ionotropic glutamate receptors.

PMID- 22948918
TI  - Structural reorganization of the bacterial cell-division protein FtsZ from
      Staphylococcus aureus.
AB  - FtsZ is a key molecule in bacterial cell division. In the presence of GTP, it
      polymerizes into tubulin-like protofilaments by head-to-tail association.
      Protofilaments of FtsZ seem to adopt a straight or a curved conformation in
      relation to the bound nucleotide. However, although several bacterial and
      archaeal FtsZ structures have been determined, all of the structures reported
      previously are considered to have a curved conformation. In this study,
      structures of FtsZ from Staphylococcus aureus (SaFtsZ) were determined in apo,
      GDP-bound and inhibitor-complex forms and it was found that SaFtsZ undergoes
      marked conformational changes. The accumulated evidence suggests that the GDP
      bound structure has the features of the straight form. The structural change
      between the curved and straight forms shows intriguing similarity to the
      eukaryotic cytoskeletal protein tubulin. Furthermore, the structure of the apo
      form showed an unexpectedly large conformational change in the core region. FtsZ
      has also been recognized as a novel target for antibacterial drugs. The structure
      of the complex with the inhibitor PC190723, which has potent and selective
      antistaphylococcal activity, indicated that the inhibitor binds at the cleft
      between the two subdomains.

PMID- 22948919
TI  - Structural analysis of the Asn152Gly mutant of P99 cephalosporinase.
AB  - P99 cephalosporinase is a class C beta-lactamase that is responsible in part for
      the widespread bacterial resistance to beta-lactam antibiotics. Mutations of the
      conserved active-site residue Asn152 of the enzyme have been shown to alter beta
      lactam substrate specificity in vivo. Mutation of Asn152 to a glycine is notable
      in that it exhibits in vivo substrate-selectivity switching. In order to better
      understand the structural basis for this observed switch, the X-ray crystal
      structure of the apo Asn152Gly mutant of P99 was determined to 1.95 A resolution.
      Unexpectedly, the artificial C-terminal His(6) tag of a symmetrically-related
      molecule was observed bound in the active site. The His(6) tag makes several
      interactions with key active-site residues, as well as with several sulfate ions.
      Additionally, the overall C-terminus occupies the space left vacant upon the
      mutation of Asn152 to glycine.

PMID- 22948920
TI  - Structure of the prolyl-tRNA synthetase from the eukaryotic pathogen Giardia
      lamblia.
AB  - The genome of the human intestinal parasite Giardia lamblia contains only a
      single aminoacyl-tRNA synthetase gene for each amino acid. The Giardia prolyl
      tRNA synthetase gene product was originally misidentified as a dual-specificity
      Pro/Cys enzyme, in part owing to its unexpectedly high off-target activation of
      cysteine, but is now believed to be a normal representative of the class of
      archaeal/eukaryotic prolyl-tRNA synthetases. The 2.2 A resolution crystal
      structure of the G. lamblia enzyme presented here is thus the first structure
      determination of a prolyl-tRNA synthetase from a eukaryote. The relative
      occupancies of substrate (proline) and product (prolyl-AMP) in the active site
      are consistent with half-of-the-sites reactivity, as is the observed biphasic
      thermal denaturation curve for the protein in the presence of proline and MgATP.
      However, no corresponding induced asymmetry is evident in the structure of the
      protein. No thermal stabilization is observed in the presence of cysteine and
      ATP. The implied low affinity for the off-target activation product cysteinyl-AMP
      suggests that translational fidelity in Giardia is aided by the rapid release of
      misactivated cysteine.

PMID- 22948921
TI  - Inhibition of D-xylose isomerase by polyols: atomic details by joint X
      ray/neutron crystallography.
AB  - D-Xylose isomerase (XI) converts the aldo-sugars xylose and glucose to their keto
      analogs xylulose and fructose, but is strongly inhibited by the polyols xylitol
      and sorbitol, especially at acidic pH. In order to understand the atomic details
      of polyol binding to the XI active site, a 2.0 A resolution room-temperature
      joint X-ray/neutron structure of XI in complex with Ni(2+) cofactors and sorbitol
      inhibitor at pH 5.9 and a room-temperature X-ray structure of XI containing
      Mg(2+) ions and xylitol at the physiological pH of 7.7 were obtained. The
      protonation of oxygen O5 of the inhibitor, which was found to be deprotonated and
      negatively charged in previous structures of XI complexed with linear glucose and
      xylulose, was directly observed. The Ni(2+) ions occupying the catalytic metal
      site (M2) were found at two locations, while Mg(2+) in M2 is very mobile and has
      a high B factor. Under acidic conditions sorbitol gains a water-mediated
      interaction that connects its O1 hydroxyl to Asp257. This contact is not found in
      structures at basic pH. The new interaction that is formed may improve the
      binding of the inhibitor, providing an explanation for the increased affinity of
      the polyols for XI at low pH.

PMID- 22948922
TI  - Induced-fit motion of a lid loop involved in catalysis in alginate lyase A1-III.
AB  - The structures of two mutants (H192A and Y246F) of a mannuronate-specific
      alginate lyase, A1-III, from Sphingomonas species A1 complexed with a
      tetrasaccharide substrate [4-deoxy-L-erythro-hex-4-ene-pyranosyluronate
      (mannuronate)(2)-mannuronic acid] were determined by X-ray crystallography at
      around 2.2 A resolution together with the apo form of the H192A mutant. The final
      models of the complex forms, which comprised two monomers (of 353 amino-acid
      residues each), 268-287 water molecules and two tetrasaccharide substrates, had R
      factors of around 0.17. A large conformational change occurred in the position of
      the lid loop (residues 64-85) in holo H192A and Y246F compared with that in apo
      H192A. The lid loop migrated about 14 A from an open form to a closed form to
      interact with the bound tetrasaccharide and a catalytic residue. The
      tetrasaccharide was bound in the active cleft at subsites -3 to +1 as a substrate
      form in which the glycosidic linkage to be cleaved existed between subsites -1
      and +1. In particular, the O(eta) atom of Tyr68 in the closed lid loop forms a
      hydrogen bond to the side chain of a presumed catalytic residue, O(eta) of
      Tyr246, which acts both as an acid and a base catalyst in a syn mechanism.

PMID- 22948923
TI  - Structure determination of enterovirus 71.
AB  - Enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may
      induce fatal neurological illness in infants and young children. Enterovirus 71
      crystallized in a body-centered orthorhombic space group with two particles in
      general orientations in the crystallographic asymmetric unit. Determination of
      the particle orientations required that the locked rotation function excluded the
      twofold symmetry axes from the set of icosahedral symmetry operators. This
      avoided the occurrence of misleading high rotation-function values produced by
      the alignment of icosahedral and crystallographic twofold axes. Once the
      orientations and positions of the particles had been established, the structure
      was solved by molecular replacement and phase extension.

PMID- 22948924
TI  - Analysis of copper-ligand bond lengths in X-ray structures of different types of
      copper sites in proteins.
AB  - An updated picture of the ligand sets and copper-ligand atom bond lengths in
      proteins is presented which takes advantage of (i) the approximately twofold
      increase in the number of entries for copper-containing proteins in the PDB since
      the last study of this kind, especially benefiting from the recent incorporation
      of the structures of proteins involved in copper homeostasis, and (ii) a
      preliminary classification of copper sites based on their structural, electronic
      and functional features. This classification allowed the calculation of reliable
      target copper-ligand distances for several bonds that were not available in
      previous work and that are in good agreement with EXAFS data and the known
      chemistry of these sites. The analysis presented here further disclosed an
      artifactual dependence of the average of the reported Cu-NHis bond lengths on
      structure resolution, highlighting the importance of taking this into account
      when computing target distances even from high-resolution structures. Finally, a
      relationship between the two Cu-O distances in bidentate carboxylates is
      disclosed, similar to that reported previously for other metal ions.

PMID- 22948925
TI  - The structure of Enterococcus faecalis thymidylate synthase provides clues about
      folate bacterial metabolism.
AB  - Drug resistance to therapeutic antibiotics poses a challenge to the
      identification of novel targets and drugs for the treatment of infectious
      diseases. Infections caused by Enterococcus faecalis are a major health problem.
      Thymidylate synthase (TS) from E. faecalis is a potential target for
      antibacterial therapy. The X-ray crystallographic structure of E. faecalis
      thymidylate synthase (EfTS), which was obtained as a native binary complex
      composed of EfTS and 5-formyltetrahydrofolate (5-FTHF), has been determined. The
      structure provides evidence that EfTS is a half-of-the-sites reactive enzyme, as
      5-FTHF is bound to two of the four independent subunits present in the crystal
      asymmetric unit. 5-FTHF is a metabolite of the one-carbon transfer reaction
      catalysed by 5-formyltetrahydrofolate cyclo-ligase. Kinetic studies show that 5
      FTHF is a weak inhibitor of EfTS, suggesting that the EfTS-5-FTHF complex may
      function as a source of folates and/or may regulate one-carbon metabolism. The
      structure represents the first example of endogenous 5-FTHF bound to a protein
      involved in folate metabolism.

PMID- 22948926
TI  - Structure of the Archaeoglobus fulgidus orphan ORF AF1382 determined by sulfur
      SAD from a moderately diffracting crystal.
AB  - The crystal structure of the 11.14 kDa orphan ORF 1382 from Archaeoglobus
      fulgidus (AF1382) has been determined by sulfur SAD phasing using a moderately
      diffracting crystal and 1.9 A wavelength synchrotron X-rays. AF1382 was selected
      as a structural genomics target by the Southeast Collaboratory for Structural
      Genomics (SECSG) since sequence analyses showed that it did not belong to the
      Pfam-A database and thus could represent a novel fold. The structure was
      determined by exploiting longer wavelength X-rays and data redundancy to increase
      the anomalous signal in the data. AF1382 is a 95-residue protein containing five
      S atoms associated with four methionine residues and a single cysteine residue
      that yields a calculated Bijvoet ratio (DeltaF(anom)/F) of 1.39% for 1.9 A
      wavelength X-rays. Coupled with an average Bijvoet redundancy of 25 (two 360
      degrees  data sets), this produced an excellent electron-density map that allowed
      69 of the 95 residues to be automatically fitted. The S-SAD model was then
      manually completed and refined (R = 23.2%, R(free) = 26.8%) to 2.3 A resolution
      (PDB entry 3o3k). High-resolution data were subsequently collected from a better
      diffracting crystal using 0.97 A wavelength synchrotron X-rays and the S-SAD
      model was refined (R = 17.9%, R(free) = 21.4%) to 1.85 A resolution (PDB entry
      3ov8). AF1382 has a winged-helix-turn-helix structure common to many DNA-binding
      proteins and most closely resembles the N-terminal domain (residues 1-82) of the
      Rio2 kinase from A. fulgidus, which has been shown to bind DNA, and a number of
      MarR-family transcriptional regulators, suggesting a similar DNA-binding function
      for AF1382. The analysis also points out the advantage gained from carrying out
      data reduction and structure determination on-site while the crystal is still
      available for further data collection.

PMID- 22948927
TI  - Experimental phasing using zinc anomalous scattering.
AB  - Zinc is a suitable metal for anomalous dispersion phasing methods in protein
      crystallography. Structure determination using zinc anomalous scattering has been
      almost exclusively limited to proteins with intrinsically bound zinc(s). Here, it
      is reported that multiple zinc ions can easily be charged onto the surface of
      proteins with no intrinsic zinc-binding site by using zinc-containing solutions.
      Zn derivatization of protein surfaces appears to be a largely unnoticed but
      promising method of protein structure determination.

PMID- 22948928
TI  - Quantifying the branching frequency of virtual filamentous microbes using fractal
      analysis.
AB  - The productivity of an industrial fermentation process involving a filamentous
      microbe is heavily dependent on the morphological form adopted by the organism.
      The development of systems capable of rapidly and accurately characterizing
      morphology within a given process represents a significant challenge, as the
      complex phenotypes that are manifested are not easily quantified. Conventional
      parameters employed in these analyses are often of limited value, as they reveal
      little about the branching behavior of the organism; an important consideration
      given the demonstrated link between branching frequency and metabolite
      production. In this study, the influence of branching behavior on the spatial
      distribution of mycelia grown in silico is examined through fractal analysis. It
      is demonstrated that fractal dimension, quantified based on the frequency
      distribution of parameterized boundary curves, and lacunarity act as robust
      estimators of branching behavior. The analysis can, in theory, be applied to any
      morphological form, providing universally applicable process parameters for more
      complete data acquisition.

PMID- 22948930
TI  - The essence of morning.

PMID- 22948931
TI  - Out-of-pocket spending in the last five years of life.
AB  - BACKGROUND: A key objective of the Medicare program is to reduce risk of
      financial catastrophe due to out-of-pocket healthcare expenditures. Yet little is
      known about cumulative financial risks arising from out-of-pocket healthcare
      expenditures faced by older adults, particularly near the end of life. DESIGN:
      Using the nationally representative Health and Retirement Study (HRS) cohort, we
      conducted retrospective analyses of Medicare beneficiaries' total out-of-pocket
      healthcare expenditures over the last 5 years of life. PARTICIPANTS: We
      identified HRS decedents between 2002 and 2008; defined a 5 year study period
      using each subject's date of death; and excluded those without Medicare coverage
      at the beginning of this period (n = 3,209). MAIN MEASURES: We examined total out
      of-pocket healthcare expenditures in the last 5 years of life and expenditures as
      a percentage of baseline household assets. We then stratified results by marital
      status and cause of death. All measurements were adjusted for inflation to 2008
      US dollars. RESULTS: Average out-of-pocket expenditures in the 5 years prior to
      death were $38,688 (95 % Confidence Interval $36,868, $40,508) for individuals,
      and $51,030 (95 % CI $47,649, $54,412) for couples in which one spouse dies.
      Spending was highly skewed, with the median and 90th percentile equal to $22,885
      and $89,106, respectively, for individuals, and $39,759 and $94,823,
      respectively, for couples. Overall, 25 % of subjects' expenditures exceeded
      baseline total household assets, and 43 % of subjects' spending surpassed their
      non-housing assets. Among those survived by a spouse, 10 % exceeded total
      baseline assets and 24 % exceeded non-housing assets. By cause of death, average
      spending ranged from $31,069 for gastrointestinal disease to $66,155 for
      Alzheimer's disease. CONCLUSION: Despite Medicare coverage, elderly households
      face considerable financial risk from out-of-pocket healthcare expenses at the
      end of life. Disease-related differences in this risk complicate efforts to
      anticipate or plan for health-related expenditures in the last 5 years of life.

PMID- 22948929
TI  - Malnutrition and obesity in pediatric oncology patients: causes, consequences,
      and interventions.
AB  - In children with cancer, suboptimal nutrition states are common consequences of
      the disease and its treatment. These nutrition states have been attributed to a
      number of etiologies dependent on the patient's tumor type and treatment, and are
      associated with increased morbidity and mortality. Interventions vary from
      psychosocial to pharmacological and surgical management. Further research is
      necessary to understand the epidemiology and etiology of these nutrition states.
      Of great importance is the development and implementation of effective
      interventions to optimize nutritional status among children with cancer during
      and after therapy.

PMID- 22948932
TI  - Differential impact of longitudinal medication non-adherence on mortality by
      race/ethnicity among veterans with diabetes.
AB  - OBJECTIVE: To examine the differential effect of medication non-adherence over
      time on all-cause mortality by race/ethnicity. RESEARCH DESIGN AND METHODS: Data
      on a longitudinal cohort of veterans with type 2 diabetes was examined. The main
      outcome was time to death. Primary independent variables were race/ethnicity and
      mean medication possession ratio (MPR) categorized into quintiles over the study
      period. Cox regression was used to model the association between time to death
      and MPR quintiles and race/ethnicity, adjusting for relevant covariates. RESULTS:
      The cohort of 629,563 veterans was followed for 5 years. After adjusting for all
      covariates, the hazard ratios (HR) for subjects in the lowest versus highest MPR
      quintile was 12.21 (95 % CI 11.89, 12.55) for non-Hispanic white (NHW), 10.01 (95
      % CI 9.18, 10.91) for non-Hispanic black (NHB), 12.65 (95 % CI 11.10, 14.43) for
      Hispanic and 10.41 (95 % CI 9.06, 11.96) for Other race veterans. Furthermore,
      type of diabetes therapy (oral versus insulin) maintained a significant
      relationship with mortality that varied by racial/ethnic group. CONCLUSIONS: This
      study demonstrates the differential impact of medication non-adherence on
      mortality by race. It also demonstrates that type of diabetes therapy (insulin
      with or without oral agents) is associated with mortality and varies by
      racial/ethnic group.

PMID- 22948936
TI  - Water desalination: Graphene cleans up water.

PMID- 22948933
TI  - Gastrointestinal events with clopidogrel: a nationwide population-based cohort
      study.
AB  - BACKGROUND: Clopidogrel prevents cardiovascular events, but has been linked with
      adverse gastrointestinal (GI) complications, particularly bleeding events.
      OBJECTIVE: We aimed to investigate the risk of adverse GI events in patients
      treated with clopidogrel. DESIGN: A nationwide population-based cohort study
      based on linkage of three administrative registries in Denmark. PARTICIPANTS: All
      individuals who redeemed at least one prescription of clopidogrel from 1996 to
      2008 were included as exposed subjects (n = 77,503). For each exposed subject,
      three matched controls were randomly selected from the background population (n =
      232,510). ANALYSES: Follow-up began on January 1, 1996, and was censored on
      December 31, 2007, or if patients emigrated or died. The study endpoint was the
      occurrence of any gastritis, GI ulcer or bleeding. Analyses were adjusted for
      comorbidity and medication. RESULTS: Regardless of dose, adjusted odds ratios
      associating clopidogrel use with the study endpoint were statistically
      significant and followed a dose-response pattern. The crude absolute risk of GI
      events were: never users: 2.2 %; <0.1 defined daily dose (DDD) of clopidogrel per
      day: 7.1 %; 0.1-0.39 DDD: 6.0 %; 0.4-0.79 DDD: 5.7 %; >=0.80 DDD: 4.4 %. Adjusted
      odds ratios were: <0.1 DDD: 1.34, 95 % CI: 1.26-1.42; 0.1-0.39 DDD: 1.58, 95 %
      CI: 1.48-1.68; 0.4-0.79 DDD: 1.91, 95 % CI: 1.77-2.06; >=0.80 DDD: 1.77, 95 % CI:
      1.66-1.89, all p-values < 0.01. Depending on the dose, numbers needed to harm
      ranged from 58 to 33 patients receiving 12 months of clopidogrel treatment.
      CONCLUSIONS: The well-known cardioprotective effect of clopidogrel must be
      carefully weighed against an increased risk of GI events.

PMID- 22948937
TI  - Nanopatterning: the chemical way to ion irradiation.

PMID- 22948938
TI  - Single-molecule magnets: Reading a nuclear spin with electrons.

PMID- 22948939
TI  - The role of mentor type and timing in predicting educational attainment.
AB  - Having an adult mentor during adolescence has been found to predict academic
      success. Building on previous work, the present study examined interactions
      between the type of mentor (i.e., kin, teacher, friend, or community), the time
      that mentor became important (i.e., before, during, or after high school), and
      the ethnicity of the protege in predicting educational attainment in young
      adulthood. Analyses used Waves III and IV of the National Longitudinal Study of
      Adolescent Health (N = 2,409). Participants' ages ranged from 18 to 27 (M =
      21.75, SD = 1.79). The sample was 56.7 % female and nationally representative of
      ethnic diversity. Analyses showed that having a teacher-mentor was more
      predictive of educational attainment than having other types of mentors and that
      overall, having a mentor after high school predicts the most educational
      attainment. Kin- and community-mentors appeared to be more important to
      educational attainment during and before high school, respectively. Findings were
      consistent across ethnic groups. Overall, results highlight the value of teacher
      mentors throughout childhood, adolescence, and early adulthood and our study
      further suggests that different types of mentors may be particularly useful at
      specific points in development.

PMID- 22948940
TI  - Electron microscopy of quasicrystals -where are the atoms?
AB  - Quasicrystals represent aperiodically ordered form of solids with symmetries long
      thought forbidden in nature. Since their discovery, the fundamental key question
      has been "where are the atoms?" in these novel aperiodic solids, and electron
      microscopy has indeed provided images of real atomic arrangements in
      quasicrystals. In this tutorial review, we describe the microscopic view of
      quasicrystals using state-of-the-art scanning transmission electron microscopy,
      providing intriguing details that had never been unveiled by the early
      diffraction-based structural analyses.

PMID- 22948941
TI  - Analysis of endogenous Oct4 activation during induced pluripotent stem cell
      reprogramming using an inducible Oct4 lineage label.
AB  - The activation of endogenous Oct4 transcription is a key step in the
      reprogramming of somatic cells into induced pluripotent stem (iPS) cells but
      until now it has been difficult to analyze this critical event in the
      reprogramming process. We have generated a transgenic mouse that expresses the
      tamoxifen-inducible Cre recombinase MerCreMer under the control of the endogenous
      Oct4 locus, enabling lineage tracing of Oct4 expression in cells in vivo or in
      vitro, during either reprogramming or differentiation. Using this novel resource,
      we have determined the timing and outcome of endogenous Oct4 induction during
      fibroblast reprogramming. We show that both the initiation of this key
      reprogramming step and the ability of cells activating endogenous Oct4 expression
      to complete reprogramming are not influenced by the presence of exogenous c-Myc,
      although the overall efficiency of the process is increased by c-Myc. Oct4
      lineage tracing reveals that new reprogramming events continue to initiate over a
      period of 3 weeks. Furthermore, the analysis of mixed colonies, where only a
      subset of daughter cells induce endogenous Oct4 expression, indicates the role of
      unknown, stochastic events in the progression of reprogramming from the initial
      events to a pluripotent state. Our transgenic mouse model and cells derived from
      it provide powerful and precise new tools for the study of iPS cell reprogramming
      mechanisms and have wider implications for the investigation of the role of Oct4
      during development.

PMID- 22948942
TI  - miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer
      cells.
AB  - Emerging evidence demonstrates that cancer stem cells (CSCs) are the critical
      drivers of tumor progression and metastasis. The microRNAs (miRNAs) may play a
      crucial role in repressing/promoting metastasis of cancer by regulating CSCs. A
      previous study showed that miR-143 and miR-145 play an important role in
      regulating bone metastasis of prostate cancer (PCa), but the exact mechanism of
      regulation of bone metastasis of PCa is not fully understood. In this study, we
      found that overexpression of miR-143 and miR-145 inhibited the cell viability and
      colony formation of PC-3 cells from PCa bone metastasis. Furthermore, miR-143 and
      miR-145 suppressed tumor sphere formation and expression of CSC markers and
      'stemness' factors including CD133, CD44, Oct4, c-Myc and Klf4 in PC-3 cells. The
      study further found that miR-143 and miR-145 inhibit bone invasion and
      tumorigenicity of PC-3 cells in vivo. Collectively, these findings demonstrate
      that miR-143 and miR-145 inhibit CSC properties of PC-3 cells and suggest that
      miR-143 and miR-145 may play a significant role in the bone metastasis
      progression of PCa by regulating CSC characteristics.

PMID- 22948943
TI  - Virgin olive oil as a source of phytoestrogens.

PMID- 22948944
TI  - Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in
      men.
AB  - BACKGROUND/OBJECTIVES: Small dense low-density lipoprotein (LDL) particles and
      apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that
      can be modulated by diet, but there is little information regarding the effects
      of dietary saturated fat on their plasma levels. We tested the effects of high vs
      low saturated fat intake in the context of a high beef protein diet on levels and
      composition of LDL subclasses and on apoCIII levels in plasma and LDL.
      SUBJECTS/METHODS: Following consumption of a baseline diet (50% carbohydrate
      (CHO), 13% protein, 38% total fat, 15% saturated fat) for 3 weeks, 14 healthy men
      were randomly assigned to two reduced CHO high beef protein diets (31% CHO, 31%
      protein, 38% fat) that differed in saturated fat content (15% vs 8%) for 3 weeks
      each in a crossover design. RESULTS: The high saturated fat (HSF) diet resulted
      in higher mass concentrations of buoyant LDL I, medium density LDL II and dense
      LDL III, but not the very dense LDL IV; and significant increases in plasma and
      LDL apoCIII concentration of 9.4% and 33.5%, respectively. The saturated fat
      induced changes in LDL apoCIII were specifically correlated with changes in
      apoCIII content of LDL IV. CONCLUSIONS: Taken together with previous
      observations, these findings suggest that, at least in the context of a lower CHO
      high beef protein diet, HSF intake may increase CVD risk by metabolic processes
      that involve apoCIII.

PMID- 22948946
TI  - A randomized controlled trial of dietetic interventions to prevent cognitive
      decline in old age hostel residents.
AB  - BACKGROUND/OBJECTIVES: To examine whether dietary interventions promote intakes
      of fruit, vegetable, fish and lower salt intake were effective in preventing
      cognitive decline in older people. Dietary factors have been associated with
      cognitive function in older people. SUBJECTS/METHODS: A total of 429 non-demented
      subjects in 14 old age hostels, with an average age of 83 years, were randomly
      assigned by hostel to have either regular group dietary counselling and menu
      changes or advice on hostel menu only. Food and salt intakes were estimated at
      regular intervals by 24-h recall or food record and fasting urinary sodium,
      respectively. The primary outcome was cognitive decline as defined by an increase
      in clinical dementia rating scale score. Secondary clinical outcomes were mini
      mental state examination, category fluency test, body weight, blood pressures and
      health-related quality of life. RESULTS: At baseline, the intervention group had
      more men and lower fish intake. When compared with control group, the
      intervention group had significantly less decline in intakes of fruit and fish.
      At month 33%, 22.2% and 27.2% of intervention and control group subjects had
      cognitive decline, respectively (Unadjusted P=0.285, chi2 test). There were no
      significant group changes in secondary clinical outcomes. On subgroup analysis,
      fewer cognitively normal subjects in intervention group had cognitive decline at
      month 24 (adjusted P=0.065). CONCLUSIONS: Dietary interventions in older people
      were effective in maintaining fruit and fish intake, but this did not lead to a
      significant reduction in cognitive decline.

PMID- 22948945
TI  - Chitin-glucan fiber effects on oxidized low-density lipoprotein: a randomized
      controlled trial.
AB  - BACKGROUND/OBJECTIVES: Elevated oxidized low-density lipoprotein (OxLDL) may
      promote inflammation, and is associated with increased risk of atherosclerotic
      coronary heart disease and worsening complications of diabetes mellitus. The
      primary objective of this study was to evaluate the efficacy of chitin-glucan
      (CG), alone and in combination with a potentially anti-inflammatory olive oil
      (OO) extract, for reducing OxLDL in subjects with borderline to high LDL
      cholesterol (LDL-C) levels. SUBJECTS/METHODS: This 6-week, randomized, double
      blind, placebo-controlled study of a novel, insoluble fiber derived from the
      Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus
      with fasting LDL-C 3.37-4.92 mmol/l and glucose <= 6.94 mmol/l. Participants were
      randomly assigned to receive CG (4.5 g/day; n=33), CG (1.5 g/day; n=32), CG (1.5
      g/day) plus OO extract (135 mg/day; n=30), or matching placebo (n=35). RESULTS:
      Administration of 4.5 g/day CG for 6 weeks significantly reduced OxLDL compared
      with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C
      levels relative to placebo, although this difference was statistically
      significant only for the CG 1.5 g/day group (P=0.019). CG did not significantly
      affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or
      F2-isoprostane levels. Adverse events did not substantively differ between
      treatments and placebo. CONCLUSIONS: In this 6-week study, CG (4.5 g/day) reduced
      OxLDL, an effect that might affect the risk for atherosclerosis.

PMID- 22948947
TI  - The relationship between level of training and accuracy of violence risk
      assessment.
AB  - OBJECTIVE: Although clinical training programs aspire to develop competency in
      violence risk assessment, little research has examined whether level of training
      is associated with the accuracy of clinicians' evaluations of violence potential.
      This is the first study to compare the accuracy of risk assessments by
      experienced psychiatrists with those performed by psychiatric residents. It also
      examined the potential of a structured decision support tool to improve
      residents' risk assessments. METHODS: The study used a retrospective case-control
      design. Medical records were reviewed for 151 patients who assaulted staff at a
      county hospital and 150 comparison patients. At admission, violence risk
      assessments had been completed by psychiatric residents (N=38) for 52 patients
      and by attending psychiatrists (N=41) for 249 patients. Trained research
      clinicians, who were blind to whether patients later became violent, coded
      information available at hospital admission by using a structured risk assessment
      tool-the Historical, Clinical, Risk Management-20 clinical subscale (HCR-20-C).
      RESULTS: Receiver operating characteristic analyses showed that clinical
      estimates of violence risk by attending psychiatrists had significantly higher
      predictive validity than those of psychiatric residents. Risk assessments by
      attending psychiatrists were moderately accurate (area under the curve
      [AUC]=.70), whereas assessments by residents were no better than chance
      (AUC=.52). Incremental validity analyses showed that addition of information from
      the HCR-20-C had the potential to improve the accuracy of risk assessments by
      residents to a level (AUC=.67) close to that of attending psychiatrists.
      CONCLUSIONS: Having less training and experience was associated with inaccurate
      violence risk assessment. Structured methods hold promise for improving training
      in risk assessment for violence.

PMID- 22948948
TI  - Associations between metabolic syndrome and syndrome components and retinal
      microvascular signs in a rural Chinese population: the Handan Eye Study.
AB  - BACKGROUND: Our purpose was to determine the relationship of metabolic syndrome
      (MetS) and its components with retinal microvascular abnormalities in a rural
      Chinese population. METHODS: The Handan Eye Study, a population-based survey,
      recruited 6,830 (90.4 % of eligible) rural Chinese >=30 years of age. A diagnosis
      of metabolic syndrome was based on the International Diabetes Federation
      definition. Retinal microvascular signs and arteriolar and venular diameters were
      assessed from fundus photographs by graders who were trained at the Retinal
      Vascular Imaging Centre, University of Melbourne. RESULTS: After adjusting for
      age, gender, and smoking status, 5,519 participants with MetS, or with the
      specific components of large waist circumference, elevated blood pressure (BP),
      or elevated fasting blood glucose (FG), were more likely to have retinopathy,
      arteriovenous nicking, focal arteriolar narrowing, enhanced arteriolar wall
      reflex, and generalized retinal arteriolar narrowing than those without MetS or
      the corresponding component. Individuals with elevated triglycerides were
      significantly more likely to have arteriovenous nicking and retinopathy.
      CONCLUSION: These results show that individual components of MetS are associated
      with different retinal microvascular signs and with changes in retinal arteriolar
      and venular diameters.

PMID- 22948949
TI  - Overestimation of subfoveal choroidal thickness by measurement based on
      horizontally compressed optical coherence tomography images.
AB  - PURPOSE: To measure the difference in subfoveal choroidal thickness between 1:1
      pixel (horizontally compressed) images and 1:1 micron images in age-related
      macular degeneration. METHODS: This study included 122 eyes from 122 patients
      diagnosed with age-related macular degeneration. Choroidal thickness was measured
      using enhanced-depth imaging optical coherence tomography. The measurement line
      was drawn as a perpendicular line between Bruch's membrane and the chorio-scleral
      interface. The thickness was compared between measurements based on a 1:1 pixel
      image and a 1:1 micron image. Eyes with a straight vertical measurement line and
      oblique measurement line were classified into vertical measurement group and
      oblique measurement group, respectively. Intra-group comparisons of subfoveal
      choroidal thickness measurements based on the 1:1 pixel images and the 1:1 micron
      images were performed for the two groups. RESULTS: The mean subfoveal choroidal
      thicknesses measured on the 1:1 pixel images and the 1:1 micron images were 232.3
      +/- 106.4 MUm and 228.9 +/- 108.1 MUm, respectively (p = 0.003). In the vertical
      measurement group (86 eyes), the mean subfoveal choroidal thickness was 226.3 +/-
      109.9 MUm and 225.4 +/- 112.0 MUm, respectively (p = 0.423). In the oblique
      measurement group (36 eyes), the thickness was 246.5 +/- 97.3 MUm and 237.5 +/-
      98.9 MUm, respectively (p < 0.001). CONCLUSIONS: Significant overestimation of
      the subfoveal choroidal thickness was noted when it was measured on a 1:1 pixel
      image. This finding suggests that the measurement of choroidal thickness should
      be performed based on a 1:1 micron image, especially if the measurement line is
      not vertical.

PMID- 22948951
TI  - Informal learning from error in hospitals: what do we learn, how do we learn and
      how can informal learning be enhanced? A narrative review.
AB  - Learning from error is not just an individual endeavour. Organisations also learn
      from error. Hospitals provide many learning opportunities, which can be formal or
      informal. Informal learning from error in hospitals has not been researched in
      much depth so this narrative review focuses on five learning opportunities:
      morbidity and mortality conferences, incident reporting systems, patient claims
      and complaints, chart review and prospective risk analysis. For each of them we
      describe: (1) what can be learnt, categorised according to the seven CanMEDS
      competencies; (2) how it is possible to learn from them, analysed against a model
      of informal and incidental learning; and (3) how this learning can be enhanced.
      All CanMEDS competencies could be enhanced, but there was a particular focus on
      the roles of medical expert and manager. Informal learning occurred mostly
      through reflection and action and was often linked to the learning of others.
      Most important to enhance informal learning from these learning opportunities was
      the realisation of a climate of collaboration and trust. Possible new directions
      for future research on informal learning from error in hospitals might focus on
      ways to measure informal learning and the balance between formal and informal
      learning. Finally, 12 recommendations about how hospitals could enhance informal
      learning within their organisation are given. 

PMID- 22948950
TI  - Comparison of observation, intravitreal bevacizumab, or pars plana vitrectomy for
      non-proliferative type 2 idiopathic macular telangiectasia.
AB  - PURPOSE: To compare visual and anatomic outcomes in eyes with type 2 idiopathic
      macular telangiectasia (Mactel) treated with either intravitreal bevacizumab
      (IVB), observation, or pars plana vitrectomy (PPV) with internal limiting
      membrane removal. METHODS: Retrospective, consecutive, interventional case series
      of phakic patients with Mactel. Best-corrected Snellen visual acuity (BCVA) and
      complete ophthalmic exam was obtained prior to treatment and at subsequent 3
      month intervals for a minimum of 6 months. Fluorescein angiographic and spectral
      domain optical coherence tomography features were examined, and compared to BCVA
      at treatment initiation and follow-up. RESULTS: Fifty-six eyes of 28 patients
      were evaluated. Mean age was 65 +/- 12 years, and mean follow-up was 24 +/- 13
      months. Patients were treated with either observation (n = 33), IVB (n = 15), or
      PPV (n = 8). Mean number of treatments for the IVB group was 2.5 +/- 3.5
      intravitreal injections. No significant differences in BCVA change were observed
      between treatment groups via one-way ANOVA (p = 0.49). Presence of inner retinal
      cysts was not correlated to BCVA (p > 0.05). Discontinuous outer nuclear layer
      was significantly related to worse initial and final vision, but not to BCVA
      change. CONCLUSION: IVB and PPV with ILM removal appear ineffective in improving
      visual outcome in eyes with non-proliferative Mactel. SD-OCT evidence of
      disrupted foveal outer nuclear layer is related to decreased BCVA, but not
      related to BCVA change following treatment.

PMID- 22948952
TI  - Addition of interferon-alpha to the p53-SLP(r) vaccine results in increased
      production of interferon-gamma in vaccinated colorectal cancer patients: a phase
      I/II clinical trial.
AB  - We previously established safety and immunogenicity of a p53 synthetic long
      peptides (p53-SLP(r)) vaccine. In the current trial, we investigated whether
      combination of interferon-alpha (IFN-alpha) with p53-SLP(r) is both safe and able
      to improve the induced p53-specific IFN-gamma response. Eleven colorectal cancer
      patients successfully treated for metastatic disease were enrolled in this study.
      Of these, nine patients completed follow-up after two injections with p53-SLP(r)
      together with IFN-alpha. Safety and p53-specific immune responses were determined
      before and after vaccination. Furthermore, cryopreserved PBMCs were compared head
      to-head to cryopreserved PBMCs obtained in our previous trial with p53-SLP(r)
      only. Toxicity of p53-SLP(r) vaccination in combination with IFN-alpha was
      limited to Grade 1 or 2, with predominantly small ongoing swellings at the
      vaccination site. All patients harbored p53-specific T cells after vaccination
      and most patients showed p53-specific antibodies. Compared to the previous trial,
      addition of IFN-alpha significantly improved the frequency of p53-specific T
      cells in IFN-gamma ELISPOT. Moreover, in this trial, p53-specific T cells were
      detectable in blood samples of all patients in a direct ex vivo multiparameter
      flowcytometric assay, opposed to only 2 of 10 patients vaccinated with p53-SLP(r)
      only. Finally, patients in this trial displayed a broader p53-specific
      immunoglobulin-G response, indicating an overall better p53-specific T-helper
      response. Our study shows that p53-SLP(r) vaccination combined with IFN-alpha
      injection is safe and capable of inducing p53-specific immunity. When compared to
      a similar trial with p53-SLP(r) vaccination alone the combination was found to
      induce significantly more IFN-gamma producing p53-specific T cells.

PMID- 22948953
TI  - Alterations of the gut microbiota in high-fat diet mice is strongly linked to
      oxidative stress.
AB  - Alterations of the gut microbiota induced by diet exert a strong influence on the
      development of metabolic syndrome. In this study, we prove the hypothesis that
      the long-term high-fat diet (HFD) may influence gut microbiota directly and/or
      indirectly by changing the redox state. Lipoic acid (LA), as a universal
      antioxidant, was used to improve the redox state. Reactive oxygen species (ROS),
      total antioxidant capacity (T-AOC), and malondialdehyde (MDA) were analyzed to
      profile oxidative stress states. PCR-denaturing gradient gel electrophoresis
      (DGGE) was used to describe gut flora structures, while plate count was employed
      for the quantitative analysis of Escherichia coli, lactobacilli, and
      enterococcus. The influence of redox state on the vitality of gut-derived
      bacteria was measured in vitro. ROS and MDA, which significantly decreased in LA
      mice compared with HFD mice, showed a strong positive association with E. coli
      and enterococcus (P < 0.05) and a negative association with lactobacilli (P <
      0.05). Increased T-AOC in LA mice showed a high positive association with
      lactobacilli (P < 0.05) and a negative correlation with E. coli and enterococcus.
      These correlations implied that the dietary effects on the gut microbiota were
      conferred, at least in part, through an effect on oxidative stress. This study
      provides evidence that modulation of the redox state by an antioxidant has the
      potential to improve gut microbiota, which has relevance for metabolic health.

PMID- 22948954
TI  - Efficient production of Japanese encephalitis virus-like particles by recombinant
      lepidopteran insect cells.
AB  - The production of Japanese encephalitis (JE) virus-like particles (VLPs) in
      stably transformed lepidopteran insect cells was investigated. The DNA fragment
      encoding the JE virus (JEV) prM signal peptide, the precursor (prM) of the viral
      membrane protein (M), and the envelope glycoprotein (E) was cloned into the
      plasmid vector pIHAbla. The pIHAbla contained the Bombyx mori actin promoter
      downstream of the B. mori nucleopolyhedrovirus (BmNPV) IE-1 transactivator and
      the BmNPV HR3 enhancer for high-level expression, together with a blasticidin
      resistance gene for use as a selectable marker. DNA encoding a form of prM with a
      pr/M cleavage site mutation was used to suppress the cell-fusion activity of
      VLPs. After transfection with the resultant plasmid, Trichoplusia ni BTI-TN-5B1-4
      (High Five) cells were incubated with blasticidin, and cells resistant to the
      antibiotic were obtained. Western blot analysis and enzyme-linked immunosorbent
      assay of a culture supernatant showed that transfected High Five cells secreted
      an E antigen equivalent to the authentic JEV E. Sucrose density-gradient
      sedimentation analysis of the culture supernatant from recombinant High Five
      cells indicated that secreted E antigen molecules were produced in a particulate
      form. VLPs recovered from the supernatant successfully induced neutralizing
      antibodies in mice, particularly when adsorbed to alum adjuvant. High yields (~30
      MUg/ml) of E antigen were achieved in shake-flask cultures. These results
      indicate that recombinant insect cells may offer a novel approach for efficient
      VLP production.

PMID- 22948955
TI  - Hydrolysis and acidification of waste-activated sludge in the presence of
      biosurfactant rhamnolipid: effect of pH.
AB  - In this investigation, the effect of pH (4.0-11.0) on waste-activated sludge
      (WAS) hydrolysis and acidification in the presence of a biosurfactant rhamnolipid
      (RL) were studied. The results showed that the hydrolysis and acidification of
      WAS in the presence of RL at alkaline pH values were more efficient than that at
      acidic and near-neutral pH values. After 6 h of hydrolysis, the soluble protein
      and carbohydrate were 1,654.7 and 675.9 mg/L (pH 11.0), and 825.6 and 376.0 mg/L
      (pH 7.0), whereas the values were only 315.0 and 84.0 mg/L at pH 4.0 and 164.1
      and 32.0 mg/L for the blank, respectively. After 2 or 3 days of fermentation, the
      accumulated short-chain fatty acids (SCFAs) reached the highest and then
      decreased with a further increase in time at all investigated pH values. The
      analysis of SCFA compositions showed that acetic, propionic, and iso-valeric
      acids were the three main products at any pH value. A higher pH contributed to a
      greater proportion of acetic acid and a lesser proportion of iso-valeric acid; a
      lower pH resulted in a greater proportion of iso-valeric and lesser proportion of
      acetic acid in the initial fermentation. The proportions of acetic acid for the
      system with biosurfactant RL addition were 16.65, 36.33, and 62.94 %,
      respectively, at pH 4.0, 7.0, and 11.0 after 1 day. Correspondingly, the
      proportions were 40.34, 12.60, and 11.01 % for iso-valeric acid.

PMID- 22948957
TI  - Predictive models for the accumulation of a fluorescent marker protein in tobacco
      leaves according to the promoter/5'UTR combination.
AB  - The promoter and 5'-untranslated region (5'UTR) play a key role in determining
      the efficiency of recombinant protein expression in plants. Comparative
      experiments are used to identify suitable elements but these are usually tested
      in transgenic plants or in transformed protoplasts/suspension cells, so their
      relevance in whole-plant transient expression systems is unclear given the
      greater heterogeneity in expression levels among different leaves. Furthermore,
      little is known about the impact of promoter/5'UTR interactions on protein
      accumulation. We therefore established a predictive model using a design of
      experiments (DoE) approach to compare the strong double-enhanced Cauliflower
      mosaic virus 35S promoter (CaMV 35SS) and the weaker Agrobacterium tumefaciens Ti
      plasmid nos promoter in whole tobacco plants transiently expressing the
      fluorescent marker protein DsRed. The promoters were combined with one of three
      5'UTRs (one of which was tested with and without an additional protein targeting
      motif) and the accumulation of DsRed was measured following different post
      agroinfiltration incubation periods in all leaves and at different leaf
      positions. The model predictions were quantitative, allowing the rapid
      identification of promoter/5'UTR combinations stimulating the highest and
      quickest accumulation of the marker protein in all leaves. The model also
      suggested that increasing the incubation time from 5 to 8 days would reduce batch
      to-batch variability in protein yields. We used the model to identify
      promoter/5'UTR pairs that resulted in the least spatiotemporal variation in
      expression levels. These ideal pairs are suitable for the simultaneous, balanced
      production of several proteins in whole plants by transient expression.

PMID- 22948956
TI  - Greater impulsivity is associated with decreased brain activation in obese women
      during a delay discounting task.
AB  - Impulsivity and poor inhibitory control are associated with higher rates of delay
      discounting (DD), or a greater preference for smaller, more immediate rewards at
      the expense of larger, but delayed rewards. Of the many functional magnetic
      resonance imaging (fMRI) studies of DD, few have investigated the correlation
      between individual differences in DD rate and brain activation related to DD
      trial difficulty, with difficult DD trials expected to activate putative
      executive function brain areas involved in impulse control. In the current study,
      we correlated patterns of brain activation as measured by fMRI during difficult
      vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was
      defined by how much a reward choice deviated from an individual's 'indifference
      point', or the point where the subjective preference for an immediate and a
      delayed reward was approximately equivalent. We found that greater delay
      discounting was correlated with less modulation of activation in putative
      executive function brain areas, such as the middle and superior frontal gyri and
      inferior parietal lobule, in response to difficult compared to easy DD trials.
      These results support the suggestion that increased impulsivity is associated
      with deficient functioning of executive function areas of the brain.

PMID- 22948958
TI  - The involvement of letter names in the silent processing of isolated letters: a
      developmental perspective.
AB  - This study was designed to clarify the nature of the mental representations
      underlying the processing of letters. A total of 96 Hebrew readers randomly
      recruited from three levels of education were asked to make rapid same/different
      judgments for Hebrew letter dyads with monosyllabic and bisyllabic names. The
      results obtained from the performance of participants under perceptual and
      conceptual processing conditions suggest that Hebrew readers access nominal
      letter representations in order to mediate letter processing in tasks that cannot
      be resolved on the basis of a sheer perceptual analysis of the letters' visual
      properties. The finding that the retrieval of nominal letter representations was
      evident for participants who differed rather markedly in their letter-processing
      speeds highlights the central role of letter names in the processing of isolated
      letters.

PMID- 22948959
TI  - The emotion-induced memory trade-off: more than an effect of overt attention?
AB  - Although it has been suggested that many effects of emotion on memory are
      attributable to attention, in the present study we addressed the hypothesis that
      such effects may relate to a number of different factors during encoding or
      postencoding. One way to look at the effects of emotion on memory is by examining
      the emotion-induced memory trade-off, whereby enhanced memory for emotional items
      often comes at the cost of memory for surrounding background information. We
      present evidence that this trade-off cannot be explained solely by overt
      attention (measured via eyetracking) directed to the emotional items during
      encoding. Participants did not devote more overt attention to emotional than to
      neutral items when those items were selectively remembered (at the expense of
      their backgrounds). Only when participants were asked to answer true/false
      questions about the items and the backgrounds--a manipulation designed to affect
      both overt attention and poststimulus elaboration--was there a reduction in
      selective emotional item memory due to an increase in background memory. These
      results indicate that the allocation of overt visual attention during encoding is
      not sufficient to predict the occurrence of selective item memory for emotional
      items.

PMID- 22948960
TI  - Reasoning as we read: establishing the probability of causal conditionals.
AB  - Indicative conditionals of the form if p then q (e.g., if student tuition fees
      rise, then applications for university places will fall) invite consideration of
      a hypothetical event (e.g., tuition fees rising) and of one of its possible
      consequences (e.g., applications falling). Since a rise in tuition fees is an
      uncertain event with equally uncertain consequences, a reader may believe the
      statement to a greater or lesser extent. As a conditional is read, the earliest
      point at which this probabilistic evaluation can take place is as the consequent
      clause is wrapped up (e.g., as the critical word fall is read in the example
      above). Wrap-up processing occurs at the end of the clause, as it is evaluated
      and integrated into the evolving discourse representation. Five sources of
      probability may plausibly influence the evaluation of a conditional as it is
      wrapped up; these are P(p), P(q), P(pq), P(q|p), and P(not-p or q). A total of
      128 conditionals were constructed, with these probabilities calculated for each
      item in a pretest. The conditionals were then embedded in vignettes and read by
      36 participants on a word-by-word basis. Using linear mixed-effects modeling, we
      found that wrap-up reading times were predicted by pretest ratings of P(p) and
      P(q|p). There was no influence of P(q), P(pq), or P(not-p or q) on wrap-up
      reading times. Our findings are consistent with the suppositional theory of
      conditionals proposed by Evans and Over (2004) but do not support the mental
      models theory advanced by Johnson-Laird and Byrne (2002).

PMID- 22948961
TI  - Long-term surgical outcomes of cervical dumbbell neurinomas.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate our treatment
      strategy for cervical dumbbell neurinoma. In treating cervical dumbbell
      neurinoma, possible difficulties include reoperation due to recurrent tumor,
      denervation due to nerve root resection, and postoperative spinal deformity due
      to extensive bony removal. METHODS: We reviewed 75 cases of cervical dumbbell
      neurinoma that were treated surgically between 1985 and 2006. Postoperative
      neurological deficits, effects of surgical margins on tumor recurrence, and
      surgical complications were investigated retrospectively. RESULTS: Sensory and
      motor deficits due to resection of specific nerve roots appeared temporarily in
      33 and 23 % of all cases, and persisted in 8 and 8 % at final evaluation,
      respectively. Total, subtotal, and partial resection was performed in 57, 13, and
      5 cases, respectively. The total resection rate was low in the tumors that had
      large extraforaminal components. Of the subtotally resected 13 cases, only two
      cases of high tumor-growth rate required re-operation or showed tumor growth.
      Among the five partially resected cases, re-operation was necessary in two cases
      13 and 15 years later because of aggravated neurological symptoms due to tumor
      growth. Two patients who underwent C2 laminectomy developed kyphosis, and three
      patients who underwent facet joint resection and curettage of vertebral body
      lesions developed scoliosis. CONCLUSION: Total resection should be attempted for
      cervical dumbbell tumors. In cases where total resection was potentially of high
      risk, however, subtotal resection (within the capsule) was found to be a
      practical choice yielding favorable long-term outcome when the tumor growth rate
      (MIB-1 index) was low.

PMID- 22948962
TI  - Uncultured adipose-derived regenerative cells promote peripheral nerve
      regeneration.
AB  - BACKGROUND: We examined whether or not peripheral nerves can be regenerated using
      uncultured adipose-derived regenerative cells (ADRCs). We also searched for
      humoral factors that might promote the proliferation or migration of Schwann
      cells. METHODS: Thirty rats were randomly assigned to three groups. A 10 mm
      sciatic nerve defect was bridged using a silicon tube filled with physiological
      saline (control group), type I collagen gel (collagen group), and a mixture of
      ADRCs and type I collagen gel (ADRC group). The regenerated tissues were studied
      two weeks after surgery. RESULTS: Continuity of regenerated tissue was observed
      in all rats in the control group and the ADRC group. In the collagen group, only
      two rats had a bridge of thin tissue, which was barely visible macroscopically.
      Protein gene product 9.5 staining confirmed significantly faster regeneration in
      the ADRC group. The distributions of the PKH-26 positive areas and the S-100
      protein positive areas were different, suggesting that the transplanted cells had
      not differentiated into Schwann cells. In real-time RT-PCR, neuregulin-1 (Neu-1)
      and vascular endothelial growth factor A (VEGFA) expression were detected in
      uncultured ADRCs before transplantation. The regenerated tissue in the ADRC group
      had higher levels of Neu-1 and VEGFA expression than the control group.
      CONCLUSIONS: ADRCs promote peripheral nerve regeneration. The mechanism does not
      involve the differentiation of transplanted cells into Schwann cells, but
      probably involves the secretion of some type of humoral factor such as Neu-1 or
      VEGFA that promotes the proliferation or migration of Schwann cells.

PMID- 22948963
TI  - KI-catalyzed imidation of sp3 C-H bond adjacent to amide nitrogen atom.
AB  - We have developed a new KI-catalyzed method for the imidation of an sp(3) C-H
      bond adjacent to an amide nitrogen atom by using TBHP (tert-butyl hydroperoxide,
      70% aqueous solution) as the oxidant. This novel procedure tolerated air and
      moisture and provided a series of novel products in moderate to excellent yields
      under mild conditions.

PMID- 22948966
TI  - Fascinating quasicrystals.

PMID- 22948965
TI  - Genome instability: does genetic diversity amplification drive tumorigenesis?
AB  - Recent data show that catastrophic events during one cell cycle can cause massive
      genome damage producing viable clones with unstable genomes. This is in contrast
      with the traditional view that tumorigenesis requires a long-term process in
      which mutations gradually accumulate over decades. These sudden events are likely
      to result in a large increase in genomic diversity within a relatively short
      time, providing the opportunity for selective advantages to be gained by a subset
      of cells within a population. This genetic diversity amplification, arising from
      a single aberrant cell cycle, may drive a population conversion from benign to
      malignant. However, there is likely a period of relative genome stability during
      the clonal expansion of tumors - this may provide an opportunity for therapeutic
      intervention, especially if mechanisms that limit tolerance of aneuploidy are
      exploited.

PMID- 22948964
TI  - An analysis of cross sectional survey data of stunting among Palestinian children
      less than five years of age.
AB  - The object of this study is to report on determinants of stunting, defined as low
      height for age, among children in the occupied Palestinian territories. Using
      2006-2007 cross sectional survey data collected by the Palestine Central Bureau
      of Statistics and using multivariate mixed model techniques for logistic
      regression, the relationships of stunting to characteristics of 9,051 Palestinian
      children less than 5 years of age living in the Palestinian territories were
      estimated. These characteristics included demographic and social characteristics
      of the child, geographic region, type of location (urban, rural, refugee camp)
      and food insecurity for each governorate. Listed in order of the greater
      contribution to the explained variation in stunting, children with lower birth
      weight (P < 0.0001), age greater than 12 months (P < 0.0001), higher levels of
      food insecurity (P < 0.0001), lower socio-economic status (P < 0.0001), mother
      illiterate (P = 0.004), urban areas (P = 0.008), and absence of supplementation
      to breast feeding during the first 4 months of the child's life (P = 0.04) have
      significantly more stunting. Children living in refugee camps have lower rates of
      stunting than urban areas; however the difference does not reach statistical
      significance. The relationship between the child's gender and stunting is not
      statistically significant. Lack of food security is directly linked to stunting.
      The continuing incidence of food insecurity means that the deleterious effects of
      under-nutrition will continue to affect the children of Palestine. Removing the
      avoidable causes of food insecurity in the occupied Palestinian territories will
      alleviate under-nutrition and its deleterious effects. 

PMID- 22948968
TI  - Doxorubicin or daunorubicin given upfront in a therapeutic window are equally
      effective in children with newly diagnosed acute lymphoblastic leukemia. A
      randomized comparison in trial CoALL 07-03.
AB  - BACKGROUND: The anthracyclines daunorubicin (DNR) and doxorubicin (DOX) are among
      the most important drugs in the treatment of childhood acute lymphoblastic
      leukemia, however there are conflicting in vitro data about the comparative
      efficacy and equivalent doses of both anthracyclines. To address the question of
      in vivo efficacy of both anthracyclines, patients enrolled in the CoALL 07-03
      trial were randomized to receive one single dose of either doxorubicin 30 mg/m(2)
      , daunorubicin 30 mg/m(2) , or daunorubicin 40 mg/m(2) upfront induction therapy.
      PROCEDURE: Children with newly diagnosed B-Precursor ALL or T-ALL were eligible
      for the randomized comparison. From the percentage of blasts and the white blood
      cell count (WBC) the absolute number of leukemic cells per ul peripheral blood
      (PB) was calculated and the initial value before DOX/DNR infusion equated as
      100%. Main target criterion of this study was the leukemic cell decrease from Day
      0 to Day 7. RESULTS: Seven hundred forty three patients were randomized: 247 to
      the DOX; 252 to the DNR 30 mg/m(2) ; and DNR to the 40 mg/m(2) arm. The in vivo
      response was similar in all three treatment arms with a comparable blast decline
      in the peripheral blood. The percentages of patients with a clear non-response
      (M3 marrow) and moreover, the level of minimal residual disease (MRD) on Day 15
      or at the end of induction were similar. CONCLUSION: In vivo efficacy of a single
      dose daunorubicin 30 or 40 mg/m(2) is similar to that of doxorubicin given in a
      dose of 30 mg/m(2) .

PMID- 22948967
TI  - Cellular heterogeneity during embryonic stem cell differentiation to epiblast
      stem cells is revealed by the ShcD/RaLP adaptor protein.
AB  - The Shc family of adaptor proteins are crucial mediators of a plethora of
      receptors such as the tyrosine kinase receptors, cytokine receptors, and
      integrins that drive signaling pathways governing proliferation, differentiation,
      and migration. Here, we report the role of the newly identified family member,
      ShcD/RaLP, whose expression in vitro and in vivo suggests a function in embryonic
      stem cell (ESC) to epiblast stem cells (EpiSCs) transition. The transition from
      the naive (ESC) to the primed (EpiSC) pluripotent state is the initial important
      step for ESCs to commit to differentiation and the mechanisms underlying this
      process are still largely unknown. Using a novel approach to simultaneously
      assess pluripotency, apoptosis, and proliferation by multiparameter flow
      cytometry, we show that ESC to EpiSC transition is a process involving a tight
      coordination between the modulation of the Oct4 expression, cell cycle
      progression, and cell death. We also describe, by high-content immunofluorescence
      analysis and time-lapse microscopy, the emergence of cells expressing caudal
      related homeobox 2 (Cdx2) transcription factor during ESC to EpiSC transition.
      The use of the ShcD knockout ESCs allowed the unmasking of this process as they
      presented deregulated Oct4 modulation and an enrichment in Oct4-negative Cdx2
      positive cells with increased MAPK/extracellular-regulated kinases 1/2
      activation, within the differentiating population. Collectively, our data reveal
      ShcD as an important modulator in the switch of key pathway(s) involved in
      determining EpiSC identity.

PMID- 22948969
TI  - Stress and neuroticism in Spanish nursing students: a two-wave longitudinal
      study.
AB  - The aim of this study was to clarify the direction of the stress-neuroticism
      relationship in a sample of 200 nursing students from three Spanish universities
      before their entry into the work force using a two-wave longitudinal design. The
      Stressful Life Events Scale and NEO-FFI Neuroticism subscale were administered at
      the beginning (T1) and end (T2) of nursing studies. Female students reported
      higher scores in both perceived stress due to life events and neuroticism than
      males. Older students scored higher in life events stress than younger ones. High
      neuroticism was associated with a high level of stress. Finally, neuroticism
      scores rose in the group in which stress increased from T1 to T2. Our findings
      partially support the stress causation interactionist model of stress in which
      life events can modify personality traits.

PMID- 22948970
TI  - Some observations on reporting quality of life in treatment of psoriasis in
      outpatient clinics.

PMID- 22948971
TI  - Biology-inspired design concepts in polymer science.

PMID- 22948973
TI  - Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer
      cells.
AB  - The antitumor activity of 7-piperazinethylchrysin (7-PEC) was investigated in HCT
      116 human colon cancer cells. MTT assay revealed that the IC50 of 7-PEC in HCT
      116 cells was 1.5 uM after 72 h of treatment, much lower than that of chrysin
      (>100 uM). The data showed that 7-PEC was able to inhibit the growth of HCT-116
      cells in a concentration- and time-dependent manner. Topical morphological
      changes of apoptotic body formation after 7-PEC treatment were observed by
      Hoechst 33258 staining. 7-PEC reduced mitochondrial membrane potential (?Psim) of
      cells in a concentration-dependent manner and increased the production of
      intracellular reactive oxygen species (ROS). After treatment with 7-PEC, a
      significant increase of Bax protein expression and decrease of Bcl-2 protein
      expression were observed at the same time. These events paralleled with
      activation of p53, caspase-3 and -9 and the release of cytochrome c (cyt-c), as
      well as poly(ADP-ribose) polymerase-1 (PARP1) cleavage and downregulation of p
      Akt. However, the apoptosis induced by 7-PEC was blocked by Ac-DEVD-CHO, a
      caspase-3 inhibitor. These results demonstrate that 7-PEC-induced mitochondrial
      dysfunction in HCT-116 human colon cancer cells triggers events responsible for
      caspase-dependent apoptosis pathways, and the elevated ratio of Bax/Bcl-2 is
      likely involved in this effect.

PMID- 22948974
TI  - Prenatal stress exposure increases the excitation of dopamine neurons in the
      ventral tegmental area and alters their reponses to psychostimulants.
AB  - Prenatal stress exposure (PSE) is known to increase addiction risk. Dopamine (DA)
      neurons in the ventral tegmental area (VTA) play an important role in addiction.
      In order to understand the cellular mechanisms underlying PSE-induced increase in
      addiction risk, we examined the effects of PSE on the electrical impulse activity
      of VTA DA neurons using the in vivo extracellular single-unit recording
      technique. Amphetamine self-administration was also conducted to confirm
      increased addiction risk after PSE. The PSE was carried out by restraining
      pregnant dams from GD 11 to 20. Adult male offspring (3-6 months old) were used
      in the experiments. Animals with PSE showed enhanced amphetamine self
      administration compared with controls when amphetamine dose was reduced after
      acquisition. The number of spontaneously active VTA DA neurons was also reduced
      in PSE rats. The reduction was reversed by acute apomorphine that normally
      inhibits the impulse activity of DA neurons. The reversal effect suggests that
      PSE-induced reduction in the number of spontaneously active VTA DA neurons is
      caused by overexcitation to the extent of depolarization block. Furthermore, the
      reduced number of spontaneously active VTA DA neurons was also reversed by acute
      psychostimulants (eg, amphetamine; cocaine), which in control rats inhibited the
      activity of VTA DA neurons. The reversal effect on VTA DA neuron in PSE animals
      represents an actual increase in the impulse activity. This effect might
      contribute to increased responding to psychostimulants and mediate increased
      addiction risk after PSE.

PMID- 22948976
TI  - Stress-induced memory retrieval impairments: different time-course involvement of
      corticosterone and glucocorticoid receptors in dorsal and ventral hippocampus.
AB  - The present study was aimed at determining the relative contribution of the
      dorsal (DH) and ventral (VH) hippocampus in stress-induced memory retrieval
      impairments. Thus, we studied the temporal involvement of corticosterone and its
      receptors, i.e. mineralocorticoid (MR) and glucocorticoid (GR) in the DH and VH,
      in relation with the time-course evolution of stress-induced memory retrieval
      impairments. In a first experiment, double microdialysis allowed showing on the
      same animal that an acute stress (electric footshocks) induced an earlier
      corticosterone rise in the DH (15-60 min post-stress) and then in the VH (90-105
      min post-stress). The return to baseline was faster in the DH (105 min) than in
      the VH (120 min). Memory deficits assessed by delayed alternation occurred at 15
      , 60-, and 105-min delays after stress and were closely related to the kinetic of
      corticosterone rises within the DH and VH. In a second experiment, the GR
      antagonist RU-38486 and the MR antagonist RU-28318 were administered in the DH or
      VH 15 min before stress. RU-38486 restored memory at 60 but not at 105 min post
      stress delays in the DH, whereas the opposite pattern was observed in the VH. By
      contrast, RU-28318 had no effect on memory impairments at both the 60- and 105
      min post-stress delays, showing that MR receptors are not involved at these
      delays. However, RU-28318 administered in the DH restored memory when
      administered at a shorter post-stress delay (15 min). Overall, our data are first
      to evidence that stress induces a functional switch from the DH to VH via
      different corticosterone time-course evolutions in these areas and the sequential
      GR receptors involvement in the DH and then in the VH, as regards the persistence
      of stress-induced memory retrieval deficits over time.

PMID- 22948977
TI  - Corticotropin-releasing factor (CRF)-induced disruption of attention in rats is
      blocked by the kappa-opioid receptor antagonist JDTic.
AB  - Stress often disrupts behavior and can lead to psychiatric illness. Considerable
      evidence suggests that corticotropin-releasing factor (CRF) plays an important
      role in regulating the effects of stress. CRF administration produces stress-like
      effects in humans and laboratory animals, and CRF levels are elevated in
      individuals with stress-related illness. Recent work indicates that kappa-opioid
      receptor (KOR) antagonists can block CRF effects, raising the possibility that at
      least some of the effects of stress are mediated via KORs. Here we examined the
      effects of CRF on performance in the 5-choice serial reaction time task (5CSRTT),
      a test used to quantify attention in rodents, as well as functional interactions
      between CRF and KORs. Male Sprague-Dawley rats were trained in the 5CSRTT and
      then each was implanted with an intracerebroventricular (ICV) cannula. After
      recovery and restabilization of performance, they received a single
      intraperitoneal (IP) injection of vehicle or JDTic (10 mg/kg), a KOR antagonist
      with long-lasting (>14 days) effects. In subsequent sessions, rats received ICV
      infusions of CRF (0.25-1.0 MUg) or vehicle and were tested 60 min later. CRF dose
      dependently disrupted performance as reflected by decreases in correct
      responding, increases in omission errors, increases in latencies to respond
      correctly, and increases in time to complete the session. JDTic attenuated each
      of these CRF-induced deficits while having no effects on its own. The persistent
      ability of JDTic to disrupt KOR function was confirmed using the tail immersion
      assay. These findings indicate that KOR antagonists can prevent acute stress
      related effects that degrade performance in tasks requiring attention.

PMID- 22948979
TI  - Heroin self-administration experience establishes control of ventral tegmental
      glutamate release by stress and environmental stimuli.
AB  - Heroin and cocaine have very different unconditioned receptor-mediated actions;
      however, in the brain circuitry of drug-reward and motivation, the two drugs
      establish common conditioned consequences. A single experience with either drug
      can change the sensitivity of ventral tegmental area (VTA) dopamine neurons to
      glutamatergic input. In the case of cocaine, repeated intravenous self
      administration establishes de novo VTA glutamate release and dopaminergic
      activation in response to conditioned stimuli and mild footshock stress. Here we
      determined whether repeated self-administration of heroin would establish similar
      glutamate release and dopaminergic activation. Although self-administration of
      heroin itself did not cause VTA glutamate release, conditioned glutamate release
      was seen when rats expecting rewarding heroin were given nonrewarding saline in
      its place. Mild footshock stress also caused glutamate release in heroin-trained
      animals. In each case, the VTA glutamate release was accompanied by elevations in
      VTA dopamine levels, indicative of dopaminergic activation. In each case,
      infusion of the ionotropic glutamate antagonist kynurenic acid blocked the VTA
      dopamine release associated with VTA glutamate elevation. Although glutamate
      levels in the extinction and reinstatement tests were similar to those reported
      in cocaine studies, the effects of heroin self-administration itself were quite
      different from what has been seen during cocaine self-administration.

PMID- 22948978
TI  - An evaluation of the evidence that methamphetamine abuse causes cognitive decline
      in humans.
AB  - Methamphetamine (MA) is one of the most commonly abused illicit substances
      worldwide. Among other problems, abuse of the drug has been associated with
      reduced cognitive function across several domains. However, much of the
      literature has not attempted to differentiate cognitive difficulties caused by MA
      abuse from preexisting cognitive difficulties that are likely caused by other
      factors. Here, we address this question, evaluating evidence for a priori
      hypotheses pertaining to six lines of research: (a) animal studies; (b) cross
      sectional human studies; (c) a twin study; (d) studies of changes in cognition
      with abstinence from MA; (e) studies of changes in brain structure and function
      with abstinence from MA; and (f) studies of the relationship between the severity
      of MA abuse and the extent of cognitive deficits observed. Overall the findings
      were mixed, with some support for a causal relationship between MA abuse and
      cognitive decline, and other findings suggesting that there is no relationship.
      The preponderance of the data, however, does support the possibility that MA
      abuse causes cognitive decline, of unknown duration, in at least some users of
      the drug. When averaged across individuals, this decline is likely to be mild in
      early-to-middle adulthood. However, moderator variables are likely to contribute
      to the presence and/or severity of cognitive decline exhibited by a given
      individual.

PMID- 22948975
TI  - The dynamics of DNA methylation in schizophrenia and related psychiatric
      disorders.
AB  - Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP)
      with psychosis (BP+) express a complex symptomatology characterized by positive
      symptoms, negative symptoms, and cognitive impairment. Postmortem studies of
      human SZ and BP+ brains show considerable alterations in the transcriptome of a
      variety of cortical structures, including multiple mRNAs that are downregulated
      in both inhibitory GABAergic and excitatory pyramidal neurons compared with non
      psychiatric subjects (NPS). Several reports show increased expression of DNA
      methyltransferases in telencephalic GABAergic neurons. Accumulating evidence
      suggests a critical role for altered DNA methylation processes in the
      pathogenesis of SZ and related psychiatric disorders. The establishment and
      maintenance of CpG site methylation is essential during central nervous system
      differentiation and this methylation has been implicated in synaptic plasticity,
      learning, and memory. Atypical hypermethylation of candidate gene promoters
      expressed in GABAergic neurons is associated with transcriptional downregulation
      of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and
      reelin (RELN). Recent reports indicate that the methylation status of promoter
      proximal CpG dinucleotides is in a dynamic balance between DNA methylation and
      DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is
      more complex and involves additional proteins downstream of 5
      hydroxymethylcytosine, including members of the base excision repair (BER)
      pathway. Recent advances in our understanding of altered CpG methylation,
      hydroxymethylation, and active DNA demethylation provide a framework for the
      identification of new targets, which may be exploited for the pharmacological
      intervention of the psychosis associated with SZ and possibly BP+.

PMID- 22948982
TI  - Giant mesenteric cyst: a rare cause of abdominal distension diagnosed with CT and
      managed with ultrasound-guided drainage.
AB  - This rare cystic lesion has an approximate incidence of 1 in 200,000. This
      patient complained of abdominal distension and was diagnosed with a giant
      mesenteric cyst measuring 26 cm in height using CT imaging. She underwent a
      successful ultrasound-guided drainage, which is not previously reported in the
      literature. This represents utilisation of an established procedure in a novel
      situation.

PMID- 22948980
TI  - Glycine transporter-1 inhibition preceding extinction training inhibits
      reacquisition of cocaine seeking.
AB  - Cognitive enhancers that act by increasing glycine transmission might be useful
      adjuncts to cocaine-cue extinction training to deter relapse. The study
      investigated the effects of combining treatments of the glycine transporter-1
      (GlyT-1) inhibitor, Org24598, with extinction training on the subsequent
      reacquisition of cocaine self-administration. Squirrel monkeys and rats were
      trained to self-administer cocaine under a second-order schedule of intravenous
      drug injection in which responding was maintained by cocaine injections and a
      cocaine-paired visual stimulus. During three weekly extinction sessions, saline
      was substituted for cocaine but responding still produced the cocaine-paired
      stimulus. Subjects were treated with Org24598 or vehicle, either before or after
      each extinction session. One week later, cocaine injections were restored, and
      reacquisition of cocaine self-administration was evaluated over 15 sessions.
      Compared with vehicle, administration of Org24598 (1.0 mg/kg in monkeys; 3.0 or
      7.5 mg/kg in rats) before each extinction session significantly inhibited
      reacquisition of cocaine self-administration in each species. In contrast,
      administration of Org24598 (1.0 mg/kg in monkeys) following, rather than
      preceding, each extinction session did not affect reacquisition compared with
      vehicle. When extinction training was replaced by cocaine self-administration or
      abstinence control conditions, treatment with the same doses of Org24598 resulted
      in reacquisition that was significantly more rapid than the reacquisition
      observed when Org24598 was administered before extinction training sessions. The
      results support the potential clinical utility of GlyT-1 inhibitor pretreatments
      combined with cocaine-cue extinction training to inhibit relapse.

PMID- 22948985
TI  - Paradoxical reaction to antitubercular therapy in miliary tuberculosis.
AB  - An 18-year-old boy presented with fever, weight loss and loss of appetite for 6
      months duration. Investigation revealed raised erythrocyte sedimentation rate,
      negative sputum smear examination for acid-fast bacilli, x-ray and high
      resolution CT chest showed bilateral, diffuse infiltration of lung parenchyma
      with miliary shadows. The patient was treated as a case of miliary tuberculosis
      with antitubercular therapy (ATT). On the 10th day of treatment the patient
      developed high-grade fever, cough and breathlessness. Chest x-ray showed an
      increased infiltration of lung parenchyma. The patient was diagnosed as a case of
      paradoxical reaction to ATT and was managed successfully with steroids.

PMID- 22948989
TI  - Inappropriate use of neurally adjusted ventilator assist.
AB  - Neurally adjusted ventilator assist (NAVA) is a ventilator mode based on
      providing assistance to the patient in proportion to the electrical activity of
      the diaphragm. NAVA may improve patient-ventilator interactions. We describe a
      very complex case of a child with a permanent ventricular assist device where we
      attempted to use NAVA during the weaning process and then realised that it was
      impossible to use.

PMID- 22948991
TI  - Focal cemento-osseous dysplasia of mandible.
AB  - Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is
      replaced by a connective tissue matrix that then gradually develops into cemento
      osseous tissue. Typically, the lesion is asymptomatic and is detected on routine
      radiographic examination. Radiologically, this lesion has three stages of
      maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque
      appearance. During these stages the lesion can be misdiagnosed. In this case
      report a 69-year- old patient with a a complaint of painless swelling of the left
      mandibular molar and premolar area is presented along with a review of the
      differential diagnoses considered in order to reach a final diagnosis of focal
      cemento-osseous dysplasia.

PMID- 22948992
TI  - Superior vena cava syndrome as a presentation of metastatic prostate cancer.
AB  - Superior vena cava (SVC) syndrome is an uncommon complication of malignant
      disease caused by the obstruction of venous blood flow in the SVC. When present,
      a diagnosis of lung cancer or lymphoma will be made in approximately 95% of
      cases. Although other malignant diseases are occasionally associated with SVC,
      its occurrence in patients with prostate cancer is rare. We present a case of a
      patient presenting with SVC obstruction who was subsequently diagnosed with
      prostate adenocarcinoma. The patient has been successfully treated with GnRH
      agonist. This case reflects the importance of a full clinical assessment and
      pathological confirmation of suspected tumour prior to treatment.

PMID- 22948993
TI  - Unusual basal ganglia lesions in a diabetic uraemic patient proven to be
      demyelination: first pathological observation.
AB  - A 64-year-old man suffering from diabetes mellitus and chronic renal failure was
      admitted to our hospital because of consciousness disturbance and parkinsonism.
      Cranial MRI showed very characteristic features involving the bilateral basal
      ganglia. Subsequent postmortem examinations demonstrated demyelination in the
      affected areas. These myelin destruction patterns were quite similar to those of
      central pontine myelinolysis. However, rapid correction of hyponatraemia was
      ruled out in this patient. Therefore, a new demyelinating brain disease
      associated with diabetes mellitus and chronic renal failure was suggested.

PMID- 22948994
TI  - Alveolar rhabdomyosarcoma with multiple distal metastases. A case report and
      review of literature.
AB  - An 18-year-old boy, presented with a history of right hip pain with movement
      restriction and proptosis of right eye. There was severe anaemia, febrile
      neutropaenia and bleeding manifestations. CT scan of right orbit documented a
      retro orbital mass. MRI revealed a mass on right side of the pelvis with
      metastatic deposits in spine. Biopsy from that mass revealed alveolar
      rhabdomyosarcoma. Bone marrow biopsy showed sarcomatous involvement with decrease
      in all three cell lineages. Chemotherapy was started according to standard
      protocol. We lost the patient after 3 weeks of initiation of chemotherapy. In our
      case, the unusual primary site and presentation with multiple distal metastases
      makes this case stand apart and therefore worth reporting.

PMID- 22948995
TI  - Severe pneumonitis after fire eating.
AB  - A 38-year-old, previously healthy fire eater presented with severe pneumonitis
      after incidental aspiration of an unquantifiable amount of petroleum. The chest
      CT revealed extensive pulmonary consolidations, and the laboratory results showed
      massively elevated inflammatory markers. An intravenous antibiotic treatment was
      started and, after improvement of symptoms and inflammatory markers, continued
      orally for a total of 3 weeks, despite negative results of blood cultures and
      urinary pneumococcal and legionella antigen tests. The patient's symptoms
      subsided completely, and a CT scan 10 weeks after the accident showed complete
      resolution of the lung consolidations. Aspiration of petroleum is associated with
      a severe inflammatory response of the lung, but if bacterial superinfection can
      be prevented with early antibiotic treatment, even a severe presentation of a
      fire eater's lung usually follows a benign course with complete recovery.

PMID- 22948996
TI  - Lung hydatid cysts.

PMID- 22948997
TI  - Intravitreal dobesilate in the treatment of choroidal neovascularisation
      associated with age-related macular degeneration: report of two cases.
AB  - This case report presents the effectiveness of intravitreal administration of
      dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients
      showing neovascular age-related macular degeneration of the classic, and of the
      occult choroidal neovascularisation types, respectively. Our study demonstrates
      that the treatment induces the regression of both forms of this pathology, as
      assessed by spectral optical coherence tomography. Improvement of the lesions was
      accompanied of visual acuity improvement.

PMID- 22948998
TI  - Vitamin B12 deficiency: an unusual cause for recurrent generalised seizures with
      pancytopaenia.
AB  - We report the case of a 70-year-old man with pancytopaenia and new-onset
      recurrent generalised seizures. Detailed evaluation yielded a diagnosis of
      vitamin B(12) deficiency. He was treated with parenteral vitamin B(12)
      supplementation and antiepileptic drugs. Seizures are an unusual manifestation of
      vitamin B(12) deficiency and possible mechanisms of epileptogenesis are
      discussed.

PMID- 22948999
TI  - Hyperglobus, do not forget the sinister.
AB  - Hyperglobus is an elevation of the ocular globe with the majority of the orbit
      remaining intact. We present a case of hyperglobus caused by a metastatic mass
      from a prostate carcinoma. There are no other reported cases in the literature.

PMID- 22949000
TI  - Giant sellar meningioma mimicking pituitary macroadenoma.

PMID- 22949001
TI  - Accidental transection of a radial artery cannula.

PMID- 22949002
TI  - Spontaneous haemorrhage and rupture of third ventricular colloid cyst.
AB  - Acute bleeding within a colloid cyst of the third ventricle represents a rare
      event causing sudden increase in the cyst volume that may lead to acute
      hydrocephalus and rapid neurological deterioration. We report a case of
      spontaneous rupture of haemorrhagic third ventricular colloid cyst and its
      management. A 77-year-old ex-smoker presented with unsteady gait, incontinence
      and gradually worsening confusion over a 3-week period. Brain CT scan findings
      were highly suggestive of a third ventricular colloid cyst with intraventricular
      rupture. He underwent cyst excision and histopathology, which confirmed the
      radiological diagnosis with evidence of haemorrhage within the cyst. A ventriculo
      peritoneal shunt was performed for delayed hydrocephalus. Surgical management of
      these patients must include emergency ventriculostomy followed by prompt surgical
      removal of the haemorrhagic cyst.

PMID- 22949003
TI  - A novel treatment of central serous chorioretinopathy with topical anti
      inflammatory therapy.
AB  - A 45-year-old Caucasian female with diagnosis of central serous chorioretinopathy
      (CSCR) did not improve on conventional observational approach. She was not
      willing to proceed with photocoagulation or photodynamic therapy. An
      unconventional approach of topical anti-inflammatory (ketorolac, dexamethasone
      and hydrocortisone) preparation was prescribed. The course of her CSCR responded
      well on this unconventional treatment, but relapsed on cessation or tapering of
      treatment. After 18 weeks of treatment with a gradual taper, her condition
      resolved. The present case highlights an alternative but unconventional treatment
      of CSCR with prolonged use of anti-inflammatories.

PMID- 22949005
TI  - Mechanism of tetralin ring opening and contraction over bifunctional Ir/SiO2
      Al2O3 Catalysts.
AB  - The development of cleaner fuels from conventional resources requires the finding
      of new hydrotreatment processes able to improve the combustion performances of
      fuels and limit undesirable emissions. In the context of gas oil upgrading by
      selective ring opening, we have investigated the hydroconversion of tetralin over
      iridium nanoparticles supported on amorphous silica-alumina. The conversion of
      tetralin leads to hydrogenation, ring-contraction, and ring-opening products. The
      selectivity to ring-opening/-contraction products (ROCPs) increases linearly with
      the acid-metal site ratio and can be tuned by modifying the metal loading, the
      metal nanoparticle size, or the support composition. From the combination of
      catalytic tests at variable conversion and the products identification by two
      dimensional gas chromatography, a mechanistic reaction scheme has been
      established. Aromatic ROCPs are formed through purely acidic steps, whereas the
      formation of saturated ROCPs mostly involves bifunctional reaction steps. Iridium
      catalyzed hydrogenolysis appears to be a minor pathway with respect to iridium
      catalyzed hydrogenation and Bronsted acid catalyzed isomerization.

PMID- 22949007
TI  - Massive flap donor sites and the role of negative pressure wound therapy.
AB  - OBJECTIVE: Report our experience with negative pressure wound therapy (NPWT)
      applied to massive scapular and latissimus free flap donor sites, in the setting
      of microvascular reconstruction for extensive head and neck defects. STUDY
      DESIGN: Retrospective case series with chart review. SETTING: Tertiary academic
      referral center. SUBJECTS AND METHODS: Retrospective review was conducted of all
      patients who underwent scapular or latissimus free tissue transfer by the senior
      author for head and neck reconstruction, over a 5-year period (2006-2011). In
      addition to NPWT details, comprehensive patient data were abstracted and
      compiled, including demographics, operative details, hospital stay, postoperative
      follow-up, and donor site complications. RESULTS: Ninety-four patients underwent
      reconstruction of extensive postablative head and neck defects using either a
      scapular or latissimus free flap. Mean harvested flap skin paddle size was 140
      cm(2). All donor sites were closed primarily. Fifty-two patients (55%) had NPWT
      applied over closed donor site incisions postoperatively. The other 42 patients
      (45%) received only conventional incision care. Major donor site complications
      occurred in 12% (n = 5) of the patients who did not undergo NPWT, as compared
      with a 6% (n = 3) complication rate among patients in the NPWT-treated group.
      CONCLUSION: This is the first study to examine NPWT in the postoperative
      treatment of closed high-tension wounds following scapular or latissimus dorsi
      harvest for reconstruction of extensive head and neck defects. Our results
      suggest that NPWT is a safe technique in the management of massive scapular and
      latissimus free flap harvest sites that may decrease associated major donor wound
      complications.

PMID- 22949008
TI  - Leg compartment syndrome after fibula free flap.

PMID- 22949009
TI  - Association between drinking water uranium content and cancer risk in Bavaria,
      Germany.
AB  - OBJECTIVE: To evaluate the possible association between uranium (U) content in
      public drinking water on the one hand and the risk of cancer of the colorectum,
      lung, female breast, prostate, kidney, and urinary bladder, total cancer, and
      leukemia on the other hand in Bavaria, an ecologic study on the level of
      municipalities was performed. METHODS: Cancer incidence data for the years 2002
      2008 were obtained from the population-based cancer registry Bavaria according to
      sex. Current U content data of public drinking water on the level of
      municipalities were obtained from a publicly available source. The possible
      association between drinking water U content and cancer risk adjusted for average
      socio-economic status was evaluated using Poisson regression. RESULTS: Drinking
      water U content was below 20 MUg/L in 458 out of 461 included municipalities. We
      found a significantly increased risk of leukemia in men in the intermediate (U
      level, 1.00-4.99 MUg/L; relative risk [RR], 1.14) and in the highest U exposure
      category (U level, >=5 MUg/L; RR, 1.28). Moreover, in women, a significantly
      elevated risk was identified with respect to kidney cancer in the highest
      exposure category (RR, 1.16) and with respect to lung cancer in the intermediate
      exposure category (RR, 1.12). CONCLUSION: The slightly increased risk of leukemia
      in men, kidney cancer in women, and lung cancer in women may require further
      investigation. If an increased cancer risk is confirmed, preventive measures
      (e.g., introduction of U filters in public water systems) may be considered.

PMID- 22949010
TI  - A less invasive surgical approach for splanchnic nerve stimulation to treat
      obesity.

PMID- 22949011
TI  - Eating behavior and glucagon-like peptide-1-producing cells in interposed ileum
      and pancreatic islets in rats subjected to ileal interposition associated with
      sleeve gastrectomy.
AB  - BACKGROUND: Ileal interposition-sleeve gastrectomy (II-SG) has been developed as
      a metabolic surgery based on the hindgut hypothesis. The aim of the present study
      was to test this hypothesis by studying the eating behavior, metabolic changes,
      and glucagon-like peptide-1 (GLP-1)-producing cells in rat models. METHODS: Male
      Sprague-Dawley rats were subjected to laparotomy, II, SG, or II-SG. Eating
      behavior and metabolic parameters were monitored by an open-circuit indirect
      calorimeter designed for a comprehensive laboratory animal monitoring system. GLP
      1-producing cells were examined by quantitative immunohistochemistry. RESULTS:
      After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced,
      while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory
      exchange ratio, VCO(2)/VO(2), was increased to above 1.0 (i.e., carbohydrate
      metabolism) during both daytime and nighttime at 2 weeks postoperatively. After
      SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms
      of volume density), but not in the ileum (number/mm). After II-SG, the rate of
      eating was reduced, while meal duration (min) was increased during both daytime
      and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by
      about 2.5-fold in the interposed ileum and also increased to the same extent in
      the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells
      in the pancreatic islets after SG or II-SG were located around the insulin
      producing beta cells. CONCLUSIONS: The present study provides evidence supporting
      the hindgut hypothesis. II-SG increased GLP-1 production both in the interposed
      ileum and in the pancreatic islets, leading to metabolic beneficial effects and
      altered eating behavior.

PMID- 22949013
TI  - Social justice and religious participation: a qualitative investigation of
      Christian perspectives.
AB  - This investigation examines how self-identified Christians in the Midwest U.S.
      understand and work for social justice, with a focus on their process of social
      justice development and the role of religious congregations in promoting social
      justice. Using a grounded theory analysis of 15 in-depth interviews, results
      indicated multiple understandings of social justice such as meeting basic needs,
      fixing social structures and systems to create equal distributions of resources,
      promoting human rights and dignity, and as a religious responsibility.
      Participants also described a process of social justice development facilitated
      by exposure to injustice, mentors, educating others, and the importance of
      finding a social justice community. Distinct personal barriers to social justice
      engagement were identified such as resources and negative emotions, whereas
      congregational leadership was important for congregational involvement. General
      frustration with congregations was expressed regarding low social justice
      engagement; however, participants balanced this frustration with hope for the
      positive potential of congregations to promote social justice. Together these
      findings show multifaceted understandings of social justice and a dynamic process
      of social justice development for these self-identified Christians. Implications
      for future research and partnership with religious individuals and congregations
      also are discussed.

PMID- 22949015
TI  - Diagnostic bias: racial and cultural issues.

PMID- 22949014
TI  - Targeting the hedgehog signal transduction pathway at the level of GLI inhibits
      neuroblastoma cell growth in vitro and in vivo.
AB  - Hedgehog (HH) signaling is an important regulator of embryogenesis that has been
      associated with the development of several types of cancer. HH signaling is
      characterized by Smoothened (SMO)-dependent activation of the GLI transcription
      factors, which regulate the expression of critical developmental genes.
      Neuroblastoma, an embryonal tumor of the sympathetic nervous system, was recently
      shown to express high levels of key molecules in this signaling cascade. Using
      compounds blocking SMO (cyclopamine and SANT1) or GLI1/GLI2 (GANT61) activity
      revealed that inhibition of HH signaling at the level of GLI was most effective
      in reducing neuroblastoma growth. GANT61 sensitivity positively correlated to
      GLI1 and negatively to MYCN expression in the neuroblastoma cell lines tested.
      GANT61 downregulated GLI1, c-MYC, MYCN and Cyclin D1 expression and induced
      apoptosis of neuroblastoma cells. The effects produced by GANT61 were mimicked by
      GLI knockdown but not by SMO knockdown. Furthermore, GANT61 enhanced the effects
      of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive
      or synergistic manner and reduced the growth of established neuroblastoma
      xenografts in nude mice. Taken together this study suggests that inhibition of HH
      signaling is a highly relevant therapeutic target for high-risk neuroblastoma
      lacking MYCN amplification and should be considered for clinical testing.

PMID- 22949017
TI  - Datapoints: Use of medications and counseling for depression by Asian and
      multiple-race adolescents aged 12-17 years.

PMID- 22949018
TI  - Public psychiatry fellowships: a developing network of public-academic
      collaborations.
AB  - In response to the expanding public behavioral health care system, a network of
      15 public-community psychiatry fellowships has developed over the past six years.
      The fellowship directors meet yearly to sustain and develop fellowships to
      recruit and retain psychiatrists in the public sector. This column describes five
      types of public-academic collaborations on which the fellowships are based. The
      collaborations focus on structural and fiscal arrangements; recruitment and
      retention; program evaluation, program research, and policy; primary care
      integration; and career development. These collaborations serve to train
      psychiatrists who will play a key role in the rapidly evolving health care
      system.

PMID- 22949019
TI  - Risk of inpatient stay for mental illness among individuals with substance use
      disorders.
AB  - OBJECTIVE: Whereas most studies of inpatient stay for mental illness examine
      whether substance use is present, this study identified types or combinations of
      abused substances that most increased hospitalization risk. METHODS: Logistic
      regression of data from the 2007 National Survey of Drug Use and Health
      (N=37,654) was used to predict past-year hospitalization of individuals with DSM
      IV substance use disorders. RESULTS: Even after the inclusion of control
      variables, adults with four types of substance abuse or dependence were more
      likely to be hospitalized than adults without substance abuse or dependence. High
      risk disorders included abuse of or dependence on opioid analgesics (odds ratio
      [OR]=6.85, p<.001), cocaine (OR=2.65, p<.05), alcohol and cocaine (OR=2.58,
      p<.05), and alcohol and marijuana (OR=3.10, p<.01). CONCLUSIONS: Researchers
      examining inpatient stays may find it beneficial to look at abuse of specific
      substances or combinations of substances, and efforts to prevent inpatient stays
      could target people with high-risk substance use disorders.

PMID- 22949020
TI  - Cross-lingual asynchronous telepsychiatry: disruptive innovation?

PMID- 22949021
TI  - Treating culturally and linguistically isolated Koreans via telepsychiatry.

PMID- 22949022
TI  - Should we try to avoid civil commitments?

PMID- 22949024
TI  - Bazelon Center guide on best-policy options for Medicaid expansion.

PMID- 22949025
TI  - Kaiser Commission brief describes Medicaid health homes.

PMID- 22949027
TI  - Microtox aquatic toxicity of petrodiesel and biodiesel blends: the role of
      biodiesel's autoxidation products.
AB  - The acute Microtox toxicity of the water accommodated fraction (WAF) of six
      commercial soybean biodiesel/petrodiesel blends was investigated at different oil
      loads. We analyzed five fatty acid methyl esters (FAMEs), C10-C24 n-alkanes, four
      aromatics, methanol, and total organic carbon (TOC) content. At high oil loads,
      the WAFs' toxicity was significantly higher for blends containing biodiesel. At
      the lowest load, the WAFs' toxicity decreased almost linearly with decreasing
      biodiesel in the blend. At intermediate loads, the WAFs of all the blends
      appeared to have a similar toxicity. Analysis of WAFs confirmed the presence of
      autoxidation byproducts of FAMEs at high oil loads. Pure unsaturated FAMEs and n
      alkanes were nontoxic when present in water at their reported solubility limits.
      However, 24-h equilibrated WAFs of pure FAMEs were highly toxic for C18:1 and
      C18:3, but not for C18:2. The authors concluded that at high oil loads, the acute
      toxicity of the WAFs was caused by FAMEs' autoxidation byproducts, whereas at low
      oil loads, the toxicity appeared to be caused primarily by the aromatic compounds
      present in petrodiesel. The addition of a synthetic antioxidant in biodiesel did
      not appear to affect the concentration of autoxidation byproducts in the WAF but
      resulted in a slight decrease in its toxicity. The major autoxidation byproducts
      identified in the WAF of commercial biodiesel were present neither in the WAFs of
      pure unsaturated FAMEs nor in the WAF of a different soybean biodiesel that was
      transesterified in our laboratory, which was nontoxic. We concluded that the
      process of transesterification of biodiesel might be a more critical factor in
      determining the aquatic toxicity of the fuel than the source of feedstock itself.

PMID- 22949028
TI  - A 3D cell culture system: separation distance between INS-1 cell and endothelial
      cell monolayers co-cultured in fibrin influences INS-1 cells insulin secretion.
AB  - The aim of this study was to develop an in vitro cell culture system allowing
      studying the effect of separation distance between monolayers of rat insulinoma
      cells (INS-1) and human umbilical vein endothelial cells (HUVEC) co-cultured in
      fibrin over INS-1 cell insulin secretion. For this purpose, a three-dimensional
      (3D) cell culture chamber was designed, built using micro-fabrication techniques
      and validated. The co-culture was successfully carried out and the effect on INS
      1 cell insulin secretion was investigated. After 48 and 72 h, INS-1 cells co
      cultured with HUVEC separated by a distance of 100 um revealed enhanced insulin
      secretion compared to INS-1 cells cultured alone or co-cultured with HUVEC
      monolayers separated by a distance of 200 um. These results illustrate the
      importance of the separation distance between two cell niches for cell culture
      design and the possibility to further enhance the endocrine function of beta
      cells when this factor is considered.

PMID- 22949029
TI  - Glucocorticoids antagonize tumor necrosis factor-alpha-stimulated lipolysis and
      resistance to the antilipolytic effect of insulin in human adipocytes.
AB  - High concentrations of TNF within obese adipose tissue increase basal lipolysis
      and antagonize insulin signaling. Adipocytes of the obese are also exposed to
      elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many
      cell types. We tested the hypothesis that TNF decreases sensitivity to the
      antilipolytic effect of insulin and that GCs antagonize this effect in
      differentiated human adipocytes. Lipolysis and expression levels of lipolytic
      proteins were measured after treating adipocytes with TNF, dexamethasone (DEX),
      or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused
      resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone
      did not significantly affect lipolysis. Cotreatment with DEX blocked TNF
      induction of basal lipolysis and insulin resistance by antagonizing TNF
      stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at
      Ser563 and Ser660 and perilipin. TNF did not affect perilipin, HSL, or
      phosphodiesterase-3B mass but paradoxically suppressed adipose tissue
      triglyceride lipase expression, and this effect was blocked by DEX. The extent to
      which GCs can restrain the lipolytic actions of TNF may both diminish the
      potentially deleterious effects of excess lipolysis and contribute to fat
      accumulation in obesity.

PMID- 22949030
TI  - Prolonged exercise training increases intramuscular lipid content and perilipin 2
      expression in type I muscle fibers of patients with type 2 diabetes.
AB  - The aim of the present study was to investigate changes in intramuscular
      triglyceride (IMTG) content and perilipin 2 expression in skeletal muscle tissue
      following 6 mo of endurance-type exercise training in type 2 diabetes patients.
      Ten obese male type 2 diabetes patients (age 62 +/- 1 yr, body mass index BMI 31
      +/- 1 kg/m2) completed three exercise sessions/week consisting of 40 min of
      continuous endurance-type exercise at 75% V(O2 peak) for a period of 6 mo. Muscle
      biopsies collected at baseline and after 2 and 6 mo of intervention were analyzed
      for IMTG content and perilipin 2 expression using fiber type-specific
      immunofluorescence microscopy. Endurance-type exercise training reduced trunk
      body fat by 6 +/- 2% and increased whole body oxygen uptake capacity by 13 +/- 7%
      (P < 0.05). IMTG content increased twofold in response to the 6 mo of exercise
      training in both type I and type II muscle fibers (P < 0.05). A threefold
      increase in perilipin 2 expression was observed from baseline to 2 and 6 mo of
      intervention in the type I muscle fibers only (1.1 +/- 0.3, 3.4 +/- 0.6, and 3.6
      +/- 0.6% of fibers stained, respectively, P < 0.05). Exercise training induced a
      1.6-fold increase in mitochondrial content after 6 mo of training in both type I
      and type II muscle fibers (P < 0.05). In conclusion, this is the first study to
      report that prolonged endurance-type exercise training increases the expression
      of perilipin 2 alongside increases in IMTG content in a type I muscle fiber-type
      specific manner in type 2 diabetes patients.

PMID- 22949031
TI  - Elevation of fibrinogen due to loss of ovarian function enhances actin ring
      formation and leads to increased bone resorption.
AB  - The aim of the present study was to evaluate the effect of fibrinogen on number
      and function of osteoclasts (OC) consequently resulting in bone loss. It was
      hypothesized that the enhanced level of released fibrinogen due to loss of
      ovarian function caused bone loss by acting on OCs. Bone loss was induced by
      ovariectomy (OVX) in mice and analyzed by micro-CT. The effect of fibrinogen on
      OCs was evaluated by tartrate-resistant acid phosphatase, annexin V, actin
      staining, pit formation observed on dentine slices, and Western blotting.
      Exogenous fibrinogen increased OC survival, actin ring formation, and bone
      resorption in vitro. The effect of fibrinogen was dependent on beta(3)-integrin,
      which is a marker for mature OCs. Fibrinogen induced the activation of
      transforming oncogene from Ak strain (Akt), Ras-related C3 botulinum toxin
      substrate 1 (Rac1), and Rho family of GTPase (Rho) and the degradation of the Bcl
      2 interacting mediator of cell death (Bim) in a manner similar to macrophage
      colony-stimulating factor (M-CSF). OVX increased plasma fibrinogen and serum M
      CSF together with elevated actin ring formation and bone loss. The increased
      fibrinogen level due to loss of ovarian function may contribute, at least partly,
      to bone loss through the enhanced number and activity of OCs.

PMID- 22949032
TI  - Interactive performance and focus groups with adolescents: the power of play.
AB  - Conducting focus groups with adolescents can be challenging given their
      developmental needs, particularly with sensitive topics. These challenges include
      intense need for peer approval, declining social trust, short attention span, and
      reliance on concrete operations thinking. In this article, we describe an
      adaptation of interactive performance as an alternative to traditional focus
      group method. We used this method in a study of discrimination experienced by
      Muslims (ages 13-17) and of peer pressure to engage in sexual behavior
      experienced by Hispanic girls (ages 10-14). Recommendations for use of this
      method include using an interdisciplinary team, planning for large amounts of
      disclosure towards the end of the focus group, and considering the fit of this
      method to the study topic.

PMID- 22949033
TI  - FAO and the One Health approach.
AB  - The Food and Agriculture Organization (FAO) of the United Nation's view on One
      Health is broad as it extends from human, animal-domestic and wildlife-and
      environmental health. Though the nidus of work originated within FAO's animal
      health service of the Agriculture and Consumer Protection Department, it is
      clearly an area of work that would include other departments such as Natural
      Resources Management and the Environment, Forestry, Fisheries and Aquaculture,
      Economic and Social Development, Legal Services, and communication. In terms of
      risk assessment and risk mitigation to health threats at the human-animal
      ecosystem interface FAO works closely with its global partners, World Health
      Organisation and the World Organisation for animal health (the "Tripartite").
      FAO's animal health service sees its work in One Health as contributing to all
      eight Millennium Development Goals, recognising the importance of animal health
      to human health, food safety, nutrition and food security, ameliorating poverty
      and hunger, natural resource management and partnerships. Some examples of FAO's
      operationalising One Health approaches or principles are introduced. 

PMID- 22949034
TI  - Changes in plasma thiol levels induced by different phases of treatment in breast
      cancer; the role of commercial extract from black chokeberry.
AB  - Different low-molecular-weight thiols, including glutathione, cysteine, and
      cysteinylglycine are physiological free radical scavengers. On the other hand,
      homocysteine may play a role as an oxidant. The aim of our present study was to
      establish in vitro the effects of the commercial extract of Aronia melanocarpa
      (Aronox((r))) on the amount of selected low-molecular-weight thiols and the
      activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase,
      and glutathione reductase) in plasma obtained from patients with invasive breast
      cancer during different phases of treatment [before or after the surgery and
      patients after different phases of chemotherapy (doxorubicin and
      cyclophosphamide)] and from healthy subjects. Patients were hospitalized in
      Department of Oncological Surgery and Department of Chemotherapy, Medical
      University of Lodz, Poland. The level of low-molecular-weight thiols was
      determined by high-performance liquid chromatography. We observed that in the
      presence of the Aronia extract changes in amount of thiols in plasma from breast
      cancer patients (at all tested groups) were significantly reduced. Our results
      showed that tested commercial extract reduced modifications of antioxidative
      enzymes activity in plasma from patients during different phases of treatment,
      but this effect was not statistical significant. Our results suggest that the
      Aronia extract supplementation in breast cancer patients has a beneficial effect
      on thiols concentration in plasma. Plasma, as reported in this work, could be
      used as an experimental model to evaluate the beneficial action of plant
      supplements, including phenolic extracts on thiols or other molecules during
      different phases of treatment.

PMID- 22949035
TI  - A retrospective analysis of real-life practice of off-label photodynamic therapy
      using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments.
      Part 1: inflammatory and aesthetic indications.
AB  - Experimental investigations have demonstrated that photodynamic therapy (PDT)
      with methyl aminolevulinate (MAL) may be a useful treatment in several
      inflammatory skin disorders and aesthetic indications. To assess the
      effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical
      practice in 20 Italian hospital centers, a retrospective observational study of
      medical records of patients treated for off-label inflammatory and aesthetic
      indications was carried out. In all patients standard treatment options had been
      either ineffective, unacceptably toxic, or medically contraindicated. Clinical
      data regarding 221 patients affected by 22 different diseases were collected. The
      most common off-label indication was acne vulgaris, with >75% improvement in
      72.8% of patients. Other disorders of the sebaceous gland, i.e. acne rosacea,
      hidradenitis suppurativa and sebaceous hyperplasia, were less responsive.
      Alopecia areata did not show any improvement. Granuloma annulare and necrobiosis
      lipoidica showed marked or moderate response in the majority of treated patients.
      The rate of patients with complete remission was lower for inflammatory skin
      disorders with hyperkeratosis, i.e. psoriasis (6/17) and porokeratosis (3/16).
      The efficacy for lichenoid dermatoses was dependent on the clinical variant
      (erosive and scleroatrophic were more responsive than hypertrophic). Only 1 of 6
      patients with Zoon balanitis had a marked improvement. MAL-PDT of venous leg
      ulcers, photo-aging and hypertrophic scars led to a marked remission in 3/5, 3/6
      and 5/8 patients, respectively. The treatment had to be interrupted because of
      strong pain and burning in 24 patients. Long term adverse events were not
      registered. Most patients with marked improvement had lasting remission with
      overall excellent cosmetic outcomes. The present findings demonstrate a high
      interest in off-label uses of MAL-PDT for inflammatory skin disorders. According
      to the observed clinical responses, safety, and favorable cosmetic results, MAL
      PDT seems to have a potential therapeutic role for the treatment of granulomatous
      dermal disorders and follicular inflammatory diseases whereas results in other
      conditions are less encouraging.

PMID- 22949036
TI  - Combination of FASP and fully automated 2D-LC-MS/MS allows in-depth proteomic
      characterization of mouse zymogen granules.
AB  - Zymogen granule (ZG) constituents play important roles in pancreatic injury and
      disease. In previous studies, proteomic analyses with rat zymogen granules were
      separated by two-dimensional gel electrophoresis or one-dimensional SDS-PAGE,
      followed by in-gel tryptic digestion. In order to overcome the disadvantage of in
      gel digestion and to carry out further in-depth proteomic analysis of the zymogen
      granules, in this study, by combining a filter-aided sample preparation method
      and fully automated 2D-LC-MS/MS technique, 800 ZG proteins were identified with
      at least two unique peptides for each protein, 75% of which have not been
      previously reported. The identified proteins revealed broad diversity in protein
      identity and function. This is the largest dataset of ZG proteome, and also the
      first dataset of the mouse ZG proteome, which may help elucidate on the molecular
      architecture of ZGs and their functions.

PMID- 22949037
TI  - Reading with a filtered fovea: the influence of visual quality at the point of
      fixation during reading.
AB  - Reading relies critically on processing text in foveal vision during brief
      fixational pauses, and high-quality visual input from foveal text is fundamental
      to theories of reading. However, the quality of visual input from foveal text
      that is actually functional for reading and the effects of this input on reading
      performance are unclear. To investigate these issues, a moving, gaze-contingent
      foveal filtering technique was developed to display areas of text within foveal
      vision that provided only coarse, medium, or fine scale visual input during each
      fixational pause during reading. Normal reading times were unaffected when foveal
      text up to three characters wide at the point of fixation provided any one visual
      input (coarse, medium, or fine). Wider areas of coarse visual input lengthened
      reading times, but reading still occurred, and normal reading times were
      completely unaffected when only medium or fine visual input extended across the
      entire fovea. Further analyses revealed that each visual input had no effect on
      the number of fixations made when normal text was read, that adjusting fixation
      durations helped preserve reading efficiency for different visual inputs, and
      that each visual input had virtually no effect on normal saccades. These findings
      indicate that, despite the resolving power of foveal vision and the emphasis
      placed on high-quality foveal visual input by theories of reading, normal reading
      functions with similar success using a range of restricted visual inputs from
      foveal text, even at the point of fixation. Some implications of these findings
      for theories of reading are discussed.

PMID- 22949038
TI  - Cutaneous lymphangitis carcinomatosis metastasis of extra-ovarian primary
      peritoneal carcinoma.

PMID- 22949039
TI  - Immunomodulation by transplanted human embryonic stem cell-derived
      oligodendroglial progenitors in experimental autoimmune encephalomyelitis.
AB  - Transplantation of embryonic stem cells and their neural derivatives can lead to
      amelioration of the disease symptoms of experimental autoimmune encephalomyelitis
      (EAE), an animal model for multiple sclerosis (MS). Oligodendroglial progenitors
      (OPs), derived from human embryonic stem cells (hESC, HES-1), were labeled with
      superparamagnetic iron oxide and transduced with luciferase. At 7 days following
      induction of EAE in C57/BL6 mice, 1 * 10(6) cells were transplanted in the
      ventricles of C57/BL6 mice and noninvasively monitored by magnetic resonance and
      bioluminescence imaging. Cells were found to remain within the cerebroventricular
      system and did not survive for more than 10 days. However, EAE mice that received
      hESC-OPs showed a significant improvement in neurological disability scores (0.9
      +/- 0.2; n = 12) compared to that of control animals (3.3 +/- 0.4; n = 12) at day
      15 post-transplantation. Histopathologically, transplanted hESC-OPs generated
      TREM2-positive CD45 cells, increased TIMP-1 expression, confined inflammatory
      cells within the subarachnoid space, and gave rise to higher numbers of Foxp3
      positive regulatory T cells in the spinal cord and spleen. Our results suggest
      that transplantation of hESC-OPs can alter the pathogenesis of EAE through
      immunomodulation, potentially providing new avenues for stem cell-based treatment
      of MS.

PMID- 22949040
TI  - Neuroprotective effect of protease-activated receptor-2 in the hypoxia-induced
      apoptosis of rat RGC-5 cells.
AB  - Hypoxia-induced apoptosis of retinal ganglion cells (RGCs) is regarded as a
      pivotal pathological process in various ocular diseases. Protease-activated
      receptor-2 (PAR-2) is involved in the regulation of cell inflammation,
      differentiation, and apoptosis in many cell types and tissues, but the role of
      PAR-2 in RGCs under pathological conditions remains unknown. The purpose of this
      study was to investigate the role of PAR-2 in the apoptosis of RGCs under hypoxic
      stress. An immortalized rat RGC line (RGC-5) was exposed to hypoxia (5 % O2). The
      expression and location of PAR-2 in RGC-5 cells under hypoxia stress were
      investigated using real-time PCR, western blotting and immunocytochemistry. Cell
      viability was determined using the Cell Counting Kit-8 assay. Apoptosis was
      detected using Hoechst 33342 staining and AnnexinV-FITC/PI assays. The role of
      Bcl-2, Bax, and the active subunit of caspase-3 was also investigated. The
      results showed that PAR-2 was functionally expressed in RGC-5 cells and up
      regulated at both mRNA and protein levels under hypoxic stress. The PAR-2
      selective agonist, SLIGRL, rescued RGC-5 cells from hypoxia-induced apoptosis
      through up-regulation of the Bcl-2/Bax ratio and down-regulation of caspase-3
      activation. This study provides the first evidence that PAR-2 has a protective
      effect against the hypoxia-induced apoptosis of RGC-5 cells.

PMID- 22949041
TI  - Aberrant expression of long noncoding RNAs in autistic brain.
AB  - The autism spectrum disorders (ASD) have a significant hereditary component, but
      the implicated genetic loci are heterogeneous and complex. Consequently, there is
      a gap in understanding how diverse genomic aberrations all result in one clinical
      ASD phenotype. Gene expression studies from autism brain tissue have demonstrated
      that aberrantly expressed protein-coding genes may converge onto common molecular
      pathways, potentially reconciling the strong heritability and shared clinical
      phenotypes with the genomic heterogeneity of the disorder. However, the
      regulation of gene expression is extremely complex and governed by many
      mechanisms, including noncoding RNAs. Yet no study in ASD brain tissue has
      assessed for changes in regulatory long noncoding RNAs (lncRNAs), which represent
      a large proportion of the human transcriptome, and actively modulate mRNA
      expression. To assess if aberrant expression of lncRNAs may play a role in the
      molecular pathogenesis of ASD, we profiled over 33,000 annotated lncRNAs and
      30,000 mRNA transcripts from postmortem brain tissue of autistic and control
      prefrontal cortex and cerebellum by microarray. We detected over 200
      differentially expressed lncRNAs in ASD, which were enriched for genomic regions
      containing genes related to neurodevelopment and psychiatric disease.
      Additionally, comparison of differences in expression of mRNAs between prefrontal
      cortex and cerebellum within individual donors showed ASD brains had more
      transcriptional homogeneity. Moreover, this was also true of the lncRNA
      transcriptome. Our results suggest that further investigation of lncRNA
      expression in autistic brain may further elucidate the molecular pathogenesis of
      this disorder.

PMID- 22949042
TI  - Automatic segmentation of episodes containing epileptic clonic seizures in video
      sequences.
AB  - Epilepsy is a neurological disorder characterized by sudden, often unexpected
      transitions from normal to pathological behavioral states called epileptic
      seizures. Some of these seizures are accompanied by uncontrolled, often rhythmic
      movements of body parts when seizure activity propagates to brain areas
      responsible for the initiation and control of movement. The dynamics of these
      transitions is, in general, unknown. As a consequence, individuals have to be
      monitored for long periods in order to obtain sufficient data for adequate
      diagnosis and to plan therapeutic strategy. Some people may require long-term
      care in special units to allow for timely intervention in case seizures get out
      of control. Our goal is to present a method by which a subset of motor seizures
      can be detected using only remote sensing devices (i.e., not in contact with the
      subject) such as video cameras. These major motor seizures (MMS) consist of
      clonic movements and are often precursors of generalized tonic-clonic
      (convulsive) seizures, sometimes leading to a condition known as status
      epilepticus, which is an acute life-threatening event. We propose an algorithm
      based on optical flow, extraction of global group transformation velocities, and
      band-pass temporal filtering to identify occurrence of clonic movements in video
      sequences. We show that for a validation set of 72 prerecorded epileptic seizures
      in 50 people, our method is highly sensitive and specific in detecting video
      segments containing MMS with clonic movements.

PMID- 22949043
TI  - Automatic feature extraction and statistical shape model of the AIDS virus spike.
AB  - We introduce a method to automatically extract spike features of the AIDS virus
      imaged through an electron microscope. The AIDS virus spike is the primary target
      of drug design as it is directly involved in infecting host cells. Our method
      detects the location of these spikes and extracts a subvolume enclosing the
      spike. We have achieved a sensitivity of 80% for our best operating range. The
      extracted spikes are further aligned and combined to build a 4-D statistical
      shape model, where each voxel in the shape model is assigned a probability
      density function. Our method is the first fully automated technique that can
      extract subvolumes of the AIDS virus spike and be used to build a statistical
      model without the need for any user supervision. We envision that this new tool
      will significantly enhance the overall process of shape analysis of the AIDS
      virus spike imaged through the electron microscope. Accurate models of the virus
      spike will help in the development of better drug design strategies.

PMID- 22949044
TI  - Simultaneous design of FIR filter banks and spatial patterns for EEG signal
      classification.
AB  - The spatial weights for electrodes called common spatial pattern (CSP) are known
      to be effective in EEG signal classification for motor imagery-based brain
      computer interface (MI-BCI). To achieve accurate classification in CSP, it is
      necessary to find frequency bands that relate to brain activities associated with
      BCI tasks. Several methods that determine such a set of frequency bands have been
      proposed. However, the existing methods cannot find the multiple frequency bands
      by using only learning data. To address this problem, we propose discriminative
      filter bank CSP (DFBCSP) that designs finite impulse response filters and the
      associated spatial weights by optimizing an objective function which is a natural
      extension of that of CSP. The optimization is conducted by sequentially and
      alternatively solving subproblems into which the original problem is divided. By
      experiments, it is shown that DFBCSP can effectively extract discriminative
      features for MI-BCI. Moreover, experimental results exhibit that DFBCSP can
      detect and extract the bands related to brain activities of motor imagery.

PMID- 22949045
TI  - Hyperstructure interactions influence the virulence of the type 3 secretion
      system in yersiniae and other bacteria.
AB  - A paradigm shift in our thinking about the intricacies of the host-parasite
      interaction is required that considers bacterial structures and their
      relationship to bacterial pathogenesis. It has been proposed that interactions
      between extended macromolecular assemblies, termed hyperstructures (which include
      multiprotein complexes), determine bacterial phenotypes. In particular, it has
      been proposed that hyperstructures can alter virulence. Two such hyperstructures
      have been characterized in both pathogenic and nonpathogenic bacteria. Present
      within a number of both human and plant Gram-negative pathogens is the type 3
      secretion system (T3SS) injectisome which in some bacteria serves to inject toxic
      effector proteins directly into targeted host cells resulting in their paralysis
      and eventual death (but which in other bacteria prevents the death of the host).
      The injectisome itself comprises multiple protein subunits, which are all
      essential for its function. The degradosome is another multiprotein complex
      thought to be involved in cooperative RNA decay and processing of mRNA
      transcripts and has been very well characterized in nonpathogenic Escherichia
      coli. Recently, experimental evidence has suggested that a degradosome exists in
      the yersiniae as well and that its interactions within the pathogens modulate
      their virulence. Here, we explore the possibility that certain interactions
      between hyperstructures, like the T3SS and the degradosome, can ultimately
      influence the virulence potential of the pathogen based upon the physical
      locations of hyperstructures within the cell.

PMID- 22949048
TI  - Breast cancer: Anastrozole and fulvestrant--combination to unlock efficacy.

PMID- 22949049
TI  - Haematological cancer: Less is more for paediatric patients--it's ALL in the
      dosing.

PMID- 22949046
TI  - The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT
      for patients with AML in remission: an integrated-risk adapted approach.
AB  - Allogeneic haematopoietic stem-cell transplantation (HSCT) is frequently applied
      as part of the treatment in patients with acute myeloid leukaemia (AML) in their
      first or subsequent remission. Allogeneic HSCT reduces relapse, but nonrelapse
      mortality and morbidity might counterbalance this beneficial effect. Here, we
      review recent studies reporting new disease-specific prognostic markers, in
      addition to allogeneic-HSCT-related risk factors, which can be assessed at
      specific time points during treatment. We propose risk assessment as a dynamic
      process during treatment, incorporating both disease-related and transplant
      related factors for the decision to proceed either to allogeneic HSCT or to apply
      a nontransplant strategy. We suggest that allogeneic HSCT might be favoured if
      the projected disease-free survival is expected to improve by at least 10% based
      on an individual's risk assessment. The approach requires initial disease risk
      assessment, identifying a sibling or unrelated donor soon after diagnosis and the
      incorporation of time-dependent risk factors, all within the context of an
      integrated therapeutic management approach.

PMID- 22949050
TI  - Lenalidomide maintenance in myeloma.

PMID- 22949051
TI  - Intrathoracic pressure oscillations during obstructive apneas disturb ventricular
      repolarisation.

PMID- 22949052
TI  - Side-chain modification and "grafting onto" via olefin cross-metathesis.
AB  - Olefin cross-metathesis is introduced as a versatile polymer side-chain
      modification technique. The reaction of a poly(2-oxazoline) featuring terminal
      double bonds in the side chains with a variety of functional acrylates has been
      successfully performed in the presence of Hoveyda-Grubbs second-generation
      catalyst. Self-metathesis, which would lead to polymer-polymer coupling, can be
      avoided by using an excess of the cross-metathesis partner and a catalyst loading
      of 5 mol%. The results suggest that bulky acrylates reduce chain-chain coupling
      due to self-metathesis. Moreover, different functional groups such as alkyl
      chains, hydroxyl, and allyl acetate groups, as well as an oligomeric
      poly(ethylene glycol) and a perfluorinated alkyl chain have been grafted with
      quantitative conversions.

PMID- 22949053
TI  - Automated delineation of calcified vessels in mammography by tracking with
      uncertainty and graphical linking techniques.
AB  - As a potential biomarker for women's cardiovascular and chronic kidney diseases,
      breast arterial calcification (BAC) in mammography has become an emerging
      research topic in recent years. To provide more objective measurement for
      vascular structures with calcium depositions in mammography, a new computerized
      method is introduced in this paper to delineate the calcified vessels.
      Specifically, we leverage two underlying cues, namely calcification and
      vesselness, into a multiple seeded tracking with uncertainty scheme. This new
      vessel-tracking scheme generates plenty of sampling paths to describe the
      complicated topology of the vascular structures with calcium depositions. A
      compiling and linking process is further carried out to organize the sampling
      paths together to be the vessel segments that likely belong to the same vessel
      tract. The proposed method has been evaluated on 63 mammograms, by comparison
      with manual delineations from two experts using various assessment metrics. The
      experiment results confirm the efficacy and stability of the proposed method, and
      also indicate that the proposed method can be potentially used as a convenient
      BAC measurement tool in replacement of the trivial and tedious manual delineation
      tasks. 

PMID- 22949054
TI  - Compressed sensing based real-time dynamic MRI reconstruction.
AB  - This work addresses the problem of real-time online reconstruction of dynamic
      magnetic resonance imaging sequences. The proposed method reconstructs the
      difference between the previous and the current image frames. This difference
      image is sparse. We recover the sparse difference image from its partial  k-space
      scans by using a nonconvex compressed sensing algorithm. As there was no previous
      fast enough algorithm for real-time reconstruction, we derive a novel algorithm
      for this purpose. Our proposed method has been compared against state-of-the-art
      offline and online reconstruction methods. The accuracy of the proposed method is
      less than offline methods but noticeably higher than the online techniques. For
      real-time reconstruction we are also concerned about the reconstruction speed.
      Our method is capable of reconstructing 128   * 128 images at the rate of 6
      frames/s, 180  *  180 images at the rate of 5 frames/s and 256   * 256 images at
      the rate of 2.5 frames/s.

PMID- 22949055
TI  - Numerical simulation of blood flow in an anatomically-accurate cerebral venous
      tree.
AB  - Although many blood flow models have been constructed for cerebral arterial
      trees, few models have been reported for their venous counterparts. In this
      paper, we present a computational model for an anatomically accurate cerebral
      venous tree which was created from a computed tomography angiography (CTA) image.
      The topology of the tree containing 42 veins was constructed with 1-D cubic
      Hermite finite element mesh. The model was formulated using the reduced Navier
      Stokes equations together with an empirical constitutive equation for the vessel
      wall which takes both distended and compressed states of the wall into account. A
      robust bifurcation model was also incorporated into the model to evaluate flow
      across branches. Furthermore, a set of hierarchal inflow pressure boundary
      conditions were prescribed to close the system of equations. Some assumptions
      were made to simplify the numerical treatment, e.g., the external pressure was
      considered as uniform across the venous tree, and a vein was either distended or
      partially collapsed but not both. Using such a scheme we were able to evaluate
      the blood flow over several cardiac cycles for the large venous tree. The
      predicted results from the model were compared with ultrasonic measurements
      acquired at several sites of the venous tree and agreements have been reached
      either qualitatively (flow waveform shape) or quantitatively (flow velocity
      magnitude). We then discuss the significance of this venous model, its potential
      applications, and also present numerical experiments pertinent to limitations of
      the proposed model.

PMID- 22949056
TI  - Phosphatidylinositol-3-kinase alpha catalytic subunit gene somatic mutations in
      bronchopulmonary neuroendocrine tumours.
AB  - Bronchopulmonary neuroendocrine tumours (BP-NETs) comprise a large spectrum of
      tumours including typical carcinoids (TCs), atypical carcinoids (ACs), large-cell
      neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) that
      exhibit considerably different biological aggressiveness and clinical behaviours.
      The phosphatidylinositol-3-kinase alpha catalytic subunit (PIK3CA) gene is known
      to be involved in the pathogenesis of several types of human cancers through gene
      amplification, deletions or somatic missense mutations within the helical and
      catalytic domains. However, the PIK3CA gene status in BP-NETs has yet to be
      explored. This study aimed to investigate the PIK3CA gene status in a large
      series of BP-NETs by direct gene sequencing and to analyse its correlation with
      the main clinicopathological parameters. To the best of our knowledge, we
      demonstrated for the first time a high frequency of somatic missense mutations
      (23.2%) in the PIK3CA gene in a series of 190 BP-NETs, including 75 TCs, 23 ACs,
      17 LCNECs and 75 SCLCs. The frequency of the PIK3CA gene mutation in the kinase
      domain was higher (17.9%) than that in the helical domain (5.3%). When the
      mutational status of the PIK3CA gene was compared with the main clinical and
      pathological characteristics of the BP-NET patients, we found a significant
      association between PIK3CA gene mutations and BP-NET histology (p=0.011).
      Interestingly, the frequency of PIK3CA gene mutations increased with the
      biological aggressiveness of all BP-NETs, except LCNECs. In conclusion, our
      results suggest that PIK3CA gene mutations may play a key role in tumourigenesis
      and aggressiveness of BP-NETs. The PIK3CA gene may represent a favourable
      candidate for an effective therapeutic strategy in the treatment of patients with
      BP-NETs.

PMID- 22949058
TI  - Visually lossless encoding for JPEG2000.
AB  - Due to exponential growth in image sizes, visually lossless coding is
      increasingly being considered as an alternative to numerically lossless coding,
      which has limited compression ratios. This paper presents a method of encoding
      color images in a visually lossless manner using JPEG2000. In order to hide
      coding artifacts caused by quantization, visibility thresholds (VTs) are measured
      and used for quantization of subband signals in JPEG2000. The VTs are
      experimentally determined from statistically modeled quantization distortion,
      which is based on the distribution of wavelet coefficients and the dead-zone
      quantizer of JPEG2000. The resulting VTs are adjusted for locally changing
      backgrounds through a visual masking model, and then used to determine the
      minimum number of coding passes to be included in the final codestream for
      visually lossless quality under the desired viewing conditions. Codestreams
      produced by this scheme are fully JPEG2000 Part-I compliant.

PMID- 22949057
TI  - Phase II study of pre-irradiation chemotherapy for childhood intracranial
      ependymoma. Children's Cancer Group protocol 9942: a report from the Children's
      Oncology Group.
AB  - PURPOSE: Standard therapy for childhood intracranial ependymoma is maximal tumor
      resection followed by involved-field irradiation. Although not used routinely,
      chemotherapy has produced objective responses in ependymoma, both at recurrence
      and in infants. Because the presence of residual tumor following surgery is
      consistently associated with inferior outcome, the potential impact of pre
      irradiation chemotherapy was investigated. METHODS: Between 1995 and 1999, the
      Children's Cancer Group undertook a Phase II trial of pre-irradiation
      chemotherapy in children 3-21 years of age with intracranial ependymoma and
      radiological evidence of post-operative residual tumor. RESULTS: Of 84 patients,
      41 had residual tumor, and were given four cycles of cisplatin-based chemotherapy
      prior to irradiation. Of 35 patients fully evaluable for response to
      chemotherapy, 14 (40%) demonstrated complete response, 6 (17%) partial response,
      10 (29%) minor response or stable disease, and 5 (14%) demonstrated progressive
      tumor growth. For the entire group, 5-year overall survival (OS) and event-free
      survival (EFS) was 71 +/- 6%, and 57 +/- 6%, respectively. The pre-irradiation
      chemotherapy group demonstrated EFS comparable to that of patients with no
      residual tumor who received irradiation alone (55 +/- 8% vs. 58 +/- 9%, P =
      0.45). Any benefit of chemotherapy was restricted to patients with greater than
      90% tumor resection. CONCLUSIONS: Children with near total resection of
      ependymoma may benefit from pre-irradiation chemotherapy. Patients with subtotal
      resection have inferior outcome despite responses to chemotherapy, and should be
      considered for second-look surgery prior to irradiation. Pediatr Blood Cancer
      2012; 59: 1183-1189. (c) 2012 Wiley Periodicals, Inc.

PMID- 22949059
TI  - Regularized discriminative spectral regression method for heterogeneous face
      matching.
AB  - Face recognition is confronted with situations in which face images are captured
      in various modalities, such as the visual modality, the near infrared modality,
      and the sketch modality. This is known as heterogeneous face recognition. To
      solve this problem, we propose a new method called discriminative spectral
      regression (DSR). The DSR maps heterogeneous face images into a common
      discriminative subspace in which robust classification can be achieved. In the
      proposed method, the subspace learning problem is transformed into a least
      squares problem. Different mappings should map heterogeneous images from the same
      class close to each other, while images from different classes should be
      separated as far as possible. To realize this, we introduce two novel
      regularization terms, which reflect the category relationships among data, into
      the least squares approach. Experiments conducted on two heterogeneous face
      databases validate the superiority of the proposed method over the previous
      methods.

PMID- 22949060
TI  - Rate-distortion analysis of dead-zone plus uniform threshold scalar quantization
      and its application--part I: fundamental theory.
AB  - This paper provides a systematic rate-distortion (R-D) analysis of the dead-zone
      plus uniform threshold scalar quantization  (DZ+UTSQ) with nearly uniform
      reconstruction quantization (NURQ) for generalized Gaussian distribution (GGD),
      which consists of two aspects: R-D performance analysis and R-D modeling. In R-D
      performance analysis, we first derive the preliminary constraint of optimum
      entropy-constrained  DZ+UTSQ/NURQ for GGD, under which the property of the GGD
      distortion-rate (D-R) function is elucidated. Then for the GGD source of actual
      transform coefficients, the refined constraint and precise conditions of optimum 
      DZ+UTSQ/NURQ are rigorously deduced in the real coding bit rate range, and
      efficient  DZ+UTSQ/NURQ design criteria are proposed to reasonably simplify the
      utilization of effective quantizers in practice. In R-D modeling, inspired by R-D
      performance analysis, the D-R function is first developed, followed by the novel
      rate-quantization (R-Q) and distortion-quantization (D-Q) models derived using
      analytical and heuristic methods. The D-R, R-Q, and D-Q models form the source
      model describing the relationship between the rate, distortion, and quantization
      steps. One application of the proposed source model is the effective two-pass VBR
      coding algorithm design on an encoder of H.264/AVC reference software, which
      achieves constant video quality and desirable rate control accuracy.

PMID- 22949061
TI  - Huber fractal image coding based on a fitting plane.
AB  - Recently, there has been significant interest in robust fractal image coding for
      the purpose of robustness against outliers. However, the known robust fractal
      coding methods (HFIC and LAD-FIC, etc.) are not optimal, since, besides the high
      computational cost, they use the corrupted domain block as the independent
      variable in the robust regression model, which may adversely affect the robust
      estimator to calculate the fractal parameters (depending on the noise level).
      This paper presents a Huber fitting plane-based fractal image coding (HFPFIC)
      method. This method builds Huber fitting planes (HFPs) for the domain and range
      blocks, respectively, ensuring the use of an uncorrupted independent variable in
      the robust model. On this basis, a new matching error function is introduced to
      robustly evaluate the best scaling factor. Meanwhile, a median absolute deviation
      (MAD) about the median decomposition criterion is proposed to achieve fast
      adaptive quadtree partitioning for the image corrupted by salt & pepper noise. In
      order to reduce computational cost, the no-search method is applied to speedup
      the encoding process. Experimental results show that the proposed HFPFIC can
      yield superior performance over conventional robust fractal image coding methods
      in encoding speed and the quality of the restored image. Furthermore, the no
      search method can significantly reduce encoding time and achieve less than 2.0 s
      for the HFPFIC with acceptable image quality degradation. In addition, we show
      that, combined with the MAD decomposition scheme, the HFP technique used as a
      robust method can further reduce the encoding time while maintaining image
      quality.

PMID- 22949062
TI  - Side information and noise learning for distributed video coding using optical
      flow and clustering.
AB  - Distributed video coding (DVC) is a coding paradigm that exploits the source
      statistics at the decoder side to reduce the complexity at the encoder. The
      coding efficiency of DVC critically depends on the quality of side information
      generation and accuracy of noise modeling. This paper considers transform domain
      Wyner-Ziv (TDWZ) coding and proposes using optical flow to improve side
      information generation and clustering to improve the noise modeling. The optical
      flow technique is exploited at the decoder side to compensate for weaknesses of
      block-based methods, when using motion-compensation to generate side information
      frames. Clustering is introduced to capture cross band correlation and increase
      local adaptivity in the noise modeling. This paper also proposes techniques to
      learn from previously decoded WZ frames. Different techniques are combined by
      calculating a number of candidate soft side information for low density parity
      check accumulate decoding. The proposed decoder side techniques for side
      information and noise learning (SING) are integrated in a TDWZ scheme. On test
      sequences, the proposed SING codec robustly improves the coding efficiency of
      TDWZ DVC. For WZ frames using a GOP size of 2, up to 4-dB improvement or an
      average (Bjontegaard) bit-rate savings of 37% is achieved compared with DISCOVER.

PMID- 22949063
TI  - Theoretical investigation on the structure and thermodynamic properties of the
      2,4-dinitroimidazole complex with methanol.
AB  - The structure and thermodynamic properties of the 2, 4-dinitroimidazole complex
      with methanol were investigated using the B3LYP and MP2(full) methods with the 6
      31++G(2d,p) and 6-311++G(3df,2p) basis sets. Four types of hydrogen bonds [N-H?O,
      C-H?O, O-H?O (nitro oxygen) and O-H?pi] were found. The hydrogen-bonded complex
      having the highest binding energy had a N-H?O hydrogen bond. Analyses of natural
      bond orbital (NBO) and atoms-in-molecules (AIM) revealed the nature of the
      intermolecular hydrogen-binding interaction. The changes in thermodynamic
      properties from monomers to complexes with temperatures ranging from 200.0 to
      800.0 K were investigated using the statistical thermodynamic method. Hydrogen
      bonded complexes of 2,4-dinitroimidazole with methanol are fostered by low
      temperatures.

PMID- 22949064
TI  - Discovery of novel low-molecular-weight HIV-1 inhibitors interacting with
      cyclophilin A using in silico screening and biological evaluations.
AB  - Cyclophilin A has attracted attention recently as a new target of anti-human
      immunodeficiency virus type 1 (HIV-1) drugs. However, so far no drug against HIV
      1 infection exhibiting this mechanism of action has been approved. To identify
      new potent candidates for inhibitors, we performed in silico screening of a
      commercial database of more than 1,300 drug-like compounds by using receptor
      based docking studies. The candidates selected from docking studies were
      subsequently tested using biological assays to assess anti-HIV activities. As a
      result, two compounds were identified as the most active. Specifically, both
      exhibited anti-HIV activity against viral replication at a low concentration and
      relatively low cytotoxicity at the effective concentration inhibiting viral
      growth by 50%. Further modification of these molecules may lead to the
      elucidation of potent inhibitors of HIV-1.

PMID- 22949065
TI  - Molecular and structural insight into plasmodium falciparum RIO2 kinase.
AB  - Among approximately 65 kinases of the malarial genome, RIO2 (right open reading
      frame) kinase belonging to the atypical class of kinase is unique because along
      with a kinase domain, it has a highly conserved N-terminal winged helix (wHTH)
      domain. The wHTH domain resembles the wing like domain found in DNA binding
      proteins and is situated near to the kinase domain. Ligand binding to this domain
      may reposition the kinase domain leading to inhibition of enzyme function and
      could be utilized as a novel allosteric site to design inhibitor. In the present
      study, we have generated a model of RIO2 kinase from Plasmodium falciparum
      utilizing multiple modeling, simulation approach. A novel putative DNA-binding
      site is identified for the first time in PfRIO2 kinase to understand the DNA
      binding events involving wHTH domain and flexible loop. Induced fit DNA docking
      followed by minimization, molecular dynamics simulation, energetic scoring and
      binding mode studies are used to reveal the structural basis of PfRIO2-ATP-DNA
      complex. Ser105 as a potential site of phosphorylation is revealed through the
      structural studies of ATP binding in PfRIO2. Overall the present study discloses
      the structural facets of unknown PfRIO2 complex and opens an avenue toward
      exploration of novel drug target.

PMID- 22949066
TI  - A B3LYP and MP2(full) theoretical investigation into the strength of the C-NO2
      bond upon the formation of the molecule-cation interaction between Na+ and the
      nitro group of nitrotriazole or its methyl derivatives.
AB  - The changes of bond dissociation energy (BDE) in the C-NO2 bond and nitro group
      charge upon the formation of the molecule-cation interaction between Na+ and the
      nitro group of 14 kinds of nitrotriazoles or methyl derivatives were investigated
      using the B3LYP and MP2(full) methods with the 6-311++G**, 6-311++G(2df,2p) and
      aug-cc-pVTZ basis sets. The strength of the C-NO2 bond was enhanced in comparison
      with that in the isolated nitrotriazole molecule upon the formation of molecule
      cation interaction. The increment of the C-NO2 bond dissociation energy
      (DeltaBDE) correlated well with the molecule-cation interaction energy. Electron
      density shifts analysis showed that the electron density shifted toward the C-NO2
      bond upon complex formation, leading to the strengthened C-NO2 bond and the
      possibly reduced explosive sensitivity.

PMID- 22949067
TI  - The first MU-Ge2Se8 ligand to lanthanide(III) centers: solvothermal syntheses and
      characterizations of lanthanide selenidogermanate complexes with a pentadentate
      polyamine as a co-ligand.
AB  - Solvothermal reactions of elements Ge and Se with Ln(2)O(3) in a pentadentate
      polyamine, tetraethylenepentamine (tepa), produced novel neutral lanthanide
      selenidogermanate polymers [{Ln(tepa)(MU-OH)}(2)(MU-Ge(2)Se(8))](n) (Ln = Eu 1,
      Gd 2, Dy 3). The reaction with Dy(2)O(3) in ethylenediamine (en) afforded an
      ionic selenidogermanate [{Dy(en)(3)}(2)(MU-OH)(2)]Ge(2)Se(6) (4). In compounds 1
      3, the Ln(3+) ions are coordinated by a tepa and two OH(-) ligands to form
      binuclear [{Ln(tepa)}(2)(MU-OH)(2)](4+) fragments. Two GeSe(4) tetrahedra are
      linked through two Se-Se bonds to form a novel [Ge(2)Se(8)](4-) unit containing a
      six-membered Ge(2)Se(4) ring in the chair conformation. The [Ge(2)Se(8)](4-) unit
      acts as a bridging ligand via the trans terminal Se atoms to interlink the
      [{Ln(tepa)}(2)(MU-OH)(2)](4+) fragments into one-dimensional polymers
      [{Ln(tepa)(MU-OH)}(2)(MU-Ge(2)Se(8))](n). Compounds 1-3 are the first examples of
      solvothermally prepared lanthanide complexes with a selenidogermanate anion as a
      ligand. The [Ge(2)Se(6)](4-) anion in 4 is composed of two GeSe(4) tetrahedra
      sharing a common edge, and is charge compensated by a [{Dy(en)(5)}(2)(MU
      OH)(2)](4+) complex cation. The formation of the [Ge(2)Se(8)](4-) and
      [Ge(2)Se(6)](4-) anions and their behavior towards lanthanide ions in 1-4 show
      the significant influence of ethylene polyamines on the solvothermal synthesis of
      Ln selenidogermanates.

PMID- 22949068
TI  - In-vitro toxicological and proteomic analysis of furan fatty acids which are
      oxidative metabolites of conjugated linoleic acids.
AB  - Furan fatty acids (furan-FA) are oxidative products of conjugated linoleic acids
      (CLA) and may therefore be ingested when CLA-containing food or food-additives
      are consumed. Due to the presence of a furan ring structure the question arises
      whether furan-FA may have toxic properties on enterocytes and liver cells. Here
      we show that furan-FA neither have toxic effects in human colon cancer cell line
      Caco-2 nor in human hepatoma cell line HepG2 at concentrations that could be
      relevant for humans. At concentrations up to 100 MUM, all tested furan-FA isomers
      showed no pronounced cytotoxicity and did not affect cellular proliferation or
      apoptosis up to concentrations of 500 MUM. In addition, furan-FA was neither
      genotoxic in the micronucleus test using Chinese hamster lung fibroblasts (V79)
      nor in the Ames test independent of the presence or absence of rat liver
      homogenate for enzymatic activation of the furan ring structure. A proteomic
      approach revealed that 48 proteins were differentially expressed when Caco-2
      cells were incubated with up to 1 mM of 10,13-epoxy-10,12-octadecadienoic acid
      (10,12-furan-FA). Three of the 30 proteins that could be identified by MALDI-TOF
      analysis were upregulated and were associated with lipid droplet biogenesis. The
      remaining 27 proteins were downregulated and were considered to be associated
      with general cellular processes such as DNA replication and transcription,
      protein biosynthesis and protein processing, lipid and energy metabolism. From
      the proteomic data we conclude that furan-FA is predominantly stored in lipid
      droplets thereby downregulating cellular metabolic activity and driving the cells
      into a state of rest.

PMID- 22949069
TI  - Delay-Induced Synchronization of Identical Linear Multiagent Systems.
AB  - This paper studies a class of fast consensus algorithms for a group of identical
      multiagent systems each described by the linear state-space model. By using both
      the current and delayed state information, the proposed delay-induced consensus
      algorithm is shown to achieve synchronization with a faster convergence speed
      than the standard one when the eigenvalues of the open-loop system, control
      parameters, the Laplacian matrix of the network, and the delay satisfy certain
      conditions. In addition, some sufficient or necessary and sufficient conditions
      are established to guarantee the closed-loop stability of the delay-induced
      consensus algorithm, where an extra control parameter on the coupling strength is
      introduced to adjust the convergence speed of the closed-loop system flexibly. We
      then show that the delay-induced algorithm is robust to the small intrinsic
      communication or input delays, i.e., the proposed delay-induced consensus
      algorithm may also produce a faster convergence speed than the standard one even
      if there exist small intrinsic communication or input delays. Furthermore, we
      extend the results from the case of an undirected communication topology to those
      of a directed communication topology and a switching communication topology.
      Several simulation examples are presented to illustrate the theoretical results. 

PMID- 22949070
TI  - Dynamic Task Assignment and Path Planning of Multi-AUV System Based on an
      Improved Self-Organizing Map and Velocity Synthesis Method in Three-Dimensional
      Underwater Workspace.
AB  - For a 3-D underwater workspace with a variable ocean current, an integrated
      multiple autonomous underwater vehicle (AUV) dynamic task assignment and path
      planning algorithm is proposed by combing the improved self-organizing map (SOM)
      neural network and a novel velocity synthesis approach. The goal is to control a
      team of AUVs to reach all appointed target locations for only one time on the
      premise of workload balance and energy sufficiency while guaranteeing the least
      total and individual consumption in the presence of the variable ocean current.
      First, the SOM neuron network is developed to assign a team of AUVs to achieve
      multiple target locations in 3-D ocean environment. The working process involves
      special definition of the initial neural weights of the SOM network, the rule to
      select the winner, the computation of the neighborhood function, and the method
      to update weights. Then, the velocity synthesis approach is applied to plan the
      shortest path for each AUV to visit the corresponding target in a dynamic
      environment subject to the ocean current being variable and targets being
      movable. Lastly, to demonstrate the effectiveness of the proposed approach,
      simulation results are given in this paper. 

PMID- 22949071
TI  - Embedding Human Expert Cognition Into Autonomous UAS Trajectory Planning.
AB  - This paper presents a new approach for the inclusion of human expert cognition
      into autonomous trajectory planning for unmanned aerial systems (UASs) operating
      in low-altitude environments. During typical UAS operations, multiple objectives
      may exist; therefore, the use of multicriteria decision aid techniques can
      potentially allow for convergence to trajectory solutions which better reflect
      overall mission requirements. In that context, additive multiattribute value
      theory has been applied to optimize trajectories with respect to multiple
      objectives. A graphical user interface was developed to allow for knowledge
      capture from a human decision maker (HDM) through simulated decision scenarios.
      The expert decision data gathered are converted into value functions and
      corresponding criteria weightings using utility additive theory. The inclusion of
      preferences elicited from HDM data within an automated decision system allows for
      the generation of trajectories which more closely represent the candidate HDM
      decision preferences. This approach has been demonstrated in this paper through
      simulation using a fixed-wing UAS operating in low-altitude environments. 

PMID- 22949072
TI  - Deep pseudocystic dermatophytosis caused by Trichophyton rubrum in a patient with
      myasthenia gravis.

PMID- 22949073
TI  - Increasing prevalence rates of HPV attributable oropharyngeal squamous cell
      carcinomas in the Netherlands as assessed by a validated test algorithm.
AB  - Human papillomavirus (HPV) infection has been etiologically linked to
      oropharyngeal squamous cell carcinoma (OPSCC). The prevalence of HPV-positive
      OPSCC varies between studies, ranging from 20 to 90%. This may be related to the
      lack of a standardized HPV detection assay as well as to the time period in which
      HPV prevalence is investigated, as rising incidence rates are reported over the
      last decades. Here, we validated our previously defined test algorithm for HPV
      detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen consisting of
      p16(INK4A)  immunostaining followed by high-risk HPV DNA detection by GP5+/6+ PCR
      on the positive cases (Smeets et al., Int J Cancer 2007;121:2465-72). In
      addition, we analyzed HPV prevalence rates in OPSCCs in the years 1990-2010. The
      test algorithm was validated on a consecutive series of 86 OPSCCs collected
      during 2008-2011, of which both fresh frozen and FFPE samples were available. We
      performed HPV-E6 RT-PCR on the frozen samples as gold standard and applied the
      algorithm to the corresponding FFPE samples. The test algorithm showed an
      accuracy of 98%. Using the validated algorithm, we determined the presence of an
      oncogenic HPV infection in 240 OPSCCs of patients diagnosed in the years 1990
      2010 at our center. A significant increase in the proportion of HPV-positive
      samples was observed, from 5.1% in 1990 to 29.0% in 2010 (p = 0.001). In
      conclusion, we confirmed the accuracy of the test algorithm for HPV detection in
      FFPE tumor specimen and we found a significant increase in the prevalence of HPV
      in OPSCC over the last two decades at our center.

PMID- 22949074
TI  - High density continuous production of murine pluripotent cells in an acoustic
      perfused bioreactor at different oxygen concentrations.
AB  - Strategies for the production of pluripotent stem cells (PSCs) rely on serially
      dissociated adherent or aggregate-based culture, consequently limiting robust
      scale-up of cell production, on-line control and optimization of culture
      conditions. We recently developed a method that enables continuous (non-serially
      dissociated) suspension culture-mediated reprogramming to pluripotency. Herein,
      we use this method to demonstrate the scalable production of PSCs and early
      derivatives using acoustic filter technology to enable continuous oxygen
      controlled perfusion culture. Cell densities of greater than 1 * 107  cells/mL
      were achieved after 7 days of expansion at a specific growth rate (u) of 0.61 +/-
      0.1 day-1 with a perfusion rate (D) of 5.0 day-1. A twofold increase in maximum
      cell density (to greater than 2.5 * 107  cells/mL) was achieved when the medium
      dissolved oxygen was reduced (5% DO). Cell densities and viabilities >80% were
      maintained for extended production periods during which maintenance of
      pluripotency was confirmed by stable expression of pluripotency factors (SSEA-1
      and Nanog), as well as the capacity to differentiate into all three germ layers.
      This work establishes a versatile biotechnological platform for the production of
      pluripotent cells and derivatives in an integrated, scalable and intensified
      stirred suspension culture.

PMID- 22949075
TI  - Analysis of imidacloprid and pyrimethanil in shallot (Allium ascalonicum) grown
      under greenhouse conditions using tandem mass spectrometry: establishment of pre
      harvest residue limits.
AB  - In this study, the original Quick, Easy, Cheap, Effective, Rugged and Safe method
      was used for the extraction of imidacloprid and pyrimethanil followed by a rapid
      clean-up through dispersive solid-phase extraction technique with primary
      secondary amine sorbent and magnesium sulfate in shallot. Residues were analyzed
      using LC-tandem mass spectrometry in positive-ion electrospray ionization mode.
      The limits of detection and quantification were estimated to be 0.006 and 0.02
      mg/kg, respectively. The samples were fortified at two different concentration
      levels (0.2 and 1.0 mg/kg), and the recoveries ranged between 79.7 and 83.9% with
      relative standard deviation values < 6%. The method was successfully applied for
      the establishment of the pre-harvest residue limits (PHRL). The rate of
      disappearance of imidacloprid and pyrimethanil on shallot was described with
      first-order kinetics (imidacloprid, y(2)  = 0.9670; pyrimethanil, y(2)  =
      0.9841), with half-lives of 2.87 and 2.08 days, respectively. Based on the
      dissipation patterns of the pesticide residues, the PHRL was recommended at 7.86
      mg/kg for 14 days (PHRL14 ) and 1.98 mg/kg for 7 days (PHRL7 ) before harvest for
      imidacloprid, and 21.64 mg/kg for 7 days (PHRL7 ) and 9.28 mg/kg for 4 days
      (PHRL4 ) before harvest for pyrimethanil in shallot.

PMID- 22949076
TI  - A retrospective analysis of real-life practice of off-label photodynamic therapy
      using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments.
      Part 2: oncologic and infectious indications.
AB  - Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) has been suggested
      as a useful treatment option in a number of skin tumors, other than approved
      indications, and infections. However, evidence is poor because it is mainly
      supported by isolated case reports or small case series, often with conflicting
      results. To assess the effectiveness, tolerability and safety of off-label MAL
      PDT in daily clinical practice in 20 Italian hospitals, a retrospective
      observational study of medical records of patients treated for off-label
      oncologic and infectious skin conditions was carried out. In all patients
      standard treatment options had been either ineffective, unacceptably toxic, or
      medically contraindicated. Clinical data from 145 patients were analyzed. Actinic
      cheilitis showed a complete remission (CR) in 27 out of 43 treated patients and
      CR was maintained at follow-up. CR was registered in 3 of 8, 5 of 8 and 10 of 17
      treated patients who were affected by extra-mammary Paget's disease (EMPD),
      erythroplasia of Queyrat (QD), and invasive squamous cell carcinoma (SCC),
      respectively. Five out of 19 patients with cutaneous T cell lymphoma had a
      complete remission. Cutaneous B-cell lymphoma, malignant fibrous histiocytoma,
      mastocytosis and nevus sebaceous were not responsive. Warts were treated in 30
      patients and 15 had a complete remission. However, periungueal and plantar
      lesions were much more responsive than flat and common lesions. Condylomata
      showed a CR in 2 out of 5 male patients but treatment was painful. Bowenoid
      papulosis showed only a partial improvement. Atypical mycobacteriosis and chronic
      cutaneous leishmaniasis were successfully treated. Submammary candidal intertrigo
      and interdigital intertrigo with Pseudomonas aeruginosa did not improve. Among
      off-label oncological uses of MAL-PDT, the therapy of actinic cheilitis was the
      most investigated and showed the best results. In addition, MAL-PDT was used
      successfully in the majority of patients with QD, EMPD and invasive SCC.
      Treatment of specific cutaneous infections was well tolerated and gave a good
      therapeutic result in a few patients, but it does not seem to give substantial
      advantages over conventional treatment options.

PMID- 22949077
TI  - Micrometer and nanometer scale photopatterning of proteins on glass surfaces by
      photo-degradation of films formed from oligo(ethylene glycol) terminated silanes.
AB  - Exposure of films formed by the adsorption of oligo(ethylene glycol) (OEG)
      functionalized trichlorosilanes on glass to UV light from a frequency-doubled
      argon ion laser (244 nm) causes photodegradation of the OEG chain. Although the
      rate of degradation is substantially slower than for monolayers of OEG terminated
      thiolates on gold, it is nevertheless possible to form micrometer-scale patterns
      by elective adsorption of streptavidin to exposed regions. A low density of
      aldehyde functional groups is produced, and this enables derivatization with
      nitrilotriacetic acid via an amine linker. Complexation with nickel enables the
      site-specific immobilization of histidine-tagged yellow and green fluorescent
      proteins. Nanometer-scale patterns may be fabricated using a Lloyd's mirror
      interferometer, with a sample and mirror set at right angles to each other. At
      low exposures, partial degradation of the OEG chains does not remove the protein
      resistance of the surface, even though friction force microscopy reveals the
      formation of patterns. At an exposure of ca. 18 J cm(-2), the modified regions
      became adhesive to proteins in a narrow region ca. 30 nm (lambda/8) wide. As the
      exposure is increased further the lines quickly broaden to ca. 90 nm. Adjustment
      of the angle between the sample and mirror enables the fabrication of lines of
      His-tagged green fluorescent protein at a period of 340 nm that could be resolved
      using a confocal microscope.

PMID- 22949078
TI  - Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming
      and maintenance: mechanisms of reprogramming and strategy for drug
      identification.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder
      characterized by progressive ossification of soft tissues. FOP is caused by
      mutations in activin receptor-like kinase 2 (ALK2) that cause its constitutive
      activation and result in dysregulation of BMP signaling. Here, we show that
      generation of induced pluripotent stem cells (iPSCs) from FOP-derived skin
      fibroblasts is repressed because of incomplete reprogramming and inhibition of
      iPSC maintenance. This repression was mostly overcome by specific suppression of
      ALK2 expression and treatment with an ALK2 inhibitor, indicating that the
      inhibition of iPSC generation and maintenance observed in FOP-derived skin
      fibroblasts results from constitutive activation of ALK2. Using this system, we
      identified an ALK2 inhibitor as a potential candidate for future drug
      development. This study highlights the potential of the inhibited production and
      maintenance of iPSCs seen in diseases as a useful phenotype not only for studying
      the molecular mechanisms underlying iPS reprogramming but also for identifying
      drug candidates for future therapies.

PMID- 22949079
TI  - 18F-Fluoride PET/CT is highly effective for excluding bone metastases even in
      patients with equivocal bone scintigraphy.
AB  - PURPOSE: Bone scintigraphy (BS) has been used extensively for many years for the
      diagnosis of bone metastases despite its low specificity and significant rate of
      equivocal lesions. (18)F-Fluoride PET/CT has been proven to have a high
      sensitivity and specificity in the detection of malignant bone lesions, but its
      effectiveness in patients with inconclusive lesions on BS is not well documented.
      This study evaluated the ability of (18)F-fluoride PET/CT to exclude bone
      metastases in patients with various malignant primary tumours and nonspecific
      findings on BS. METHODS: We prospectively studied 42 patients (34-88 years of
      age, 26 women) with different types of tumour. All patients had BS performed for
      staging or restaging purposes but with inconclusive findings. All patients
      underwent (18)F-fluoride PET/CT. All abnormalities identified on BS images were
      visually compared with their appearance on the PET/CT images. RESULTS: All the 96
      inconclusive lesions found on BS images of the 42 patients were identified on
      PET/CT images. (18)F-Fluoride PET/CT correctly excluded bone metastases in 23
      patients (68 lesions). Of 19 patients (28 lesions) classified by PET/CT as having
      metastases, 3 (5 lesions) were finally classified as free of bone metastases on
      follow-up. The sensitivity, specificity, and positive and negative predictive
      values of (18)F-fluoride PET/CT were, respectively, 100 %, 88 %, 84 % and 100 %
      for the identification of patients with metastases (patient analysis) and 100 %,
      82 % and 100 % for the identification of metastatic lesions (lesion analysis).
      CONCLUSION: The factors that make BS inconclusive do not affect (18)F-fluoride
      PET/CT which shows a high sensitivity and negative predictive value for excluding
      bone metastases even in patients with inconclusive conventional BS.

PMID- 22949080
TI  - Nuclear cardiology at the door of a new era: better to save mSv or to reduce
      imaging time?

PMID- 22949081
TI  - SPECT/CT imaging in 99mTc-HSA-DTPA gastrointestinal bleeding scintigraphy to
      localize bleeding sites.

PMID- 22949082
TI  - SPECT/CT arthrography of the knee.

PMID- 22949083
TI  - Childhood narcolepsy- a rare disorder.

PMID- 22949084
TI  - A knowledge editing service for multisource data management in remote health
      monitoring.
AB  - Remote Health Monitoring (RHM) programmes are being increasingly developed to
      face the pervasive diffusion of chronic diseases. RHM strongly relies on ICT
      intelligent platforms devised to remotely acquire multisource data, process these
      according to specific domain knowledge and support clinical decision making.
      However, since RHM domain is continuously evolving and the pertinent knowledge is
      not yet consolidated, there is a great demand for services and tools that allow
      the encoded knowledge to be modified and enriched. This paper presents a
      Knowledge Editing Service (KES), which aims at enabling clinicians to insert
      novel knowledge, in a controlled fashion, into an ICT intelligent platform. The
      solution proposed is innovative since it addresses synergistically peculiar
      issues related to (i) RHM knowledge format; (ii) controlled editing patterns;
      (iii) knowledge verification and (iv) cooperative knowledge editing. None of the
      existing methods and systems for knowledge authoring tackles all these aspects at
      the same time. A prototype of the KES has been implemented and evaluated in real
      operational conditions. 

PMID- 22949085
TI  - WiiPD--objective home assessment of Parkinson's disease using the Nintendo Wii
      remote.
AB  - Current clinical methods for the assessment of Parkinson's disease suffer from
      inconvenience, infrequency and subjectivity. WiiPD is an approach for the
      objective home based assessment of Parkinson's disease which utilizes the
      intuitive and sensor rich Nintendo Wii Remote. Combined with an electronic
      patient diary, a suite of mini-games, a metric analyzer, and a visualization
      engine, we propose that this system can complement existing clinical practice by
      providing objective metrics gathered frequently over extended periods of time. In
      this paper we detail the approach and introduce a series of metrics deemed
      capable of quantifying the severity of tremor and bradykinesia in those with
      Parkinson's disease. The system has been tested on a 71 year old participant with
      Parkinson's disease over a period of 15 days, a 72 year old control user without
      Parkinson's disease, and a group of 8 young adults. Results indicate a clear
      correlation between patient self rating scores of tremor severity and metric
      values obtained, in addition to clear differences in metrics obtained from each
      user group. These results suggest that this approach is capable of indicating the
      presence and severity of the motor symptoms of Parkinson's disease that affect
      arm motor control. 

PMID- 22949086
TI  - Independent association between obstructive sleep apnea and noncalcified coronary
      plaque demonstrated by noninvasive coronary computed tomography angiography.
AB  - BACKGROUND: Coronary artery atherosclerosis has been associated with obstructive
      sleep apnea (OSA). However, the type and severity of plaque formation have not
      been characterized. This study evaluated the association of coronary noncalcified
      plaques and severity of stenosis in patients with OSA. HYPOTHESIS:  METHODS: This
      study was a retrospective analysis of 81 patients, 49 with OSA and 32 without
      OSA, who had undergone multidetector-row helical computed tomography scanning.
      The board-certified radiologist was blinded to the diagnosis of OSA and reviewed
      the scans for plaque characterization, severity of stenosis, and number of
      vessels involved. RESULTS: Of the 81 patients reviewed, the mean apnea-hypopnea
      index in the OSA group was 42.2 vs 7.5 in the non-OSA group. The groups did not
      significantly differ in the distribution of comorbid conditions. We found that
      among the patients with OSA, 63% had noncalcified/mixed plaques, as opposed to
      16% in the non-OSA group (P < 0.0001), with unadjusted odds ratio of 9.3 (3.0,
      28.4). After adjustment for other risk factors such as age, sex, race,
      hypercholesterolemia, and history of smoking, the association remained strong,
      with an odds ratio of 7.0 (1.9, 26.5; P < 0.05). CONCLUSIONS: Our study finds
      that the frequency of noncalcified/mixed plaques is much higher in patients with
      OSA than in non-OSA patients. Patients with OSA also have more severe stenosis
      and a higher number of vessels involved. This study adds to a growing body of
      data regarding our understanding of the association of OSA and atherosclerosis.

PMID- 22949087
TI  - Chemical and toxicological assessment of a full-scale biosolid compost.
AB  - The impact of a full-scale biosolid composting plant on the fate of a broad range
      of priority organic pollutants was investigated. Chemical analysis was performed
      at different steps of the process during two seasons. Simultaneously, the
      toxicological quality was assessed using estrogen alpha-, dioxin-, and pregnane X
      receptor reporter cell lines. Mass-balance calculation highlighted the removal of
      easily degradable pollutants during composting. The important variations observed
      for each compound and for the two seasons might be explained by pollutant-fate
      dependency on process parameters like temperature. The final compost displayed
      low pregnane X activity but high estrogenic activity. The dioxin-like activity
      stayed constant through the process. The chemical and toxicological results
      highlight the importance of combining both approaches to accurately assess the
      compost quality. Such compilation of data on full-scale processes may be also
      very helpful for the environmental risk assessment of new organic waste disposal
      practices.

PMID- 22949088
TI  - Pulmonary exacerbations in cystic fibrosis: young children with characteristic
      signs and symptoms.
AB  - BACKGROUND: A standard definition of pulmonary exacerbation based on signs and
      symptoms would be useful for categorizing cystic fibrosis (CF) patients and as an
      outcome measure of therapy. The frequently used definition of treatment with
      intravenous antibiotics varies with practice patterns. One approach to this
      problem is to use large data sets which include a patient's signs and symptoms
      along with their clinician's decision to treat with antibiotics for the diagnosis
      of pulmonary exacerbation. Previous analysis of such a data set, the
      Epidemiologic Study of Cystic Fibrosis (ESCF), found that new crackles, increased
      cough, increased sputum, and weight decline were the four clinical
      characteristics most strongly influencing providers to treat young CF patients
      for a pulmonary exacerbation. The objectives of this study were to confirm that
      these four characteristics influence the decision to treat with antibiotics for a
      pulmonary exacerbation in young CF patients; to evaluate their implications for
      future nutritional status and lung function; and to assess the effect of
      antibiotic treatment on these characteristic signs and symptoms. METHODS: This
      was an observational, longitudinal cohort study of clinical care in children <6
      years old cared for at sites participating in ESCF. RESULTS: Using data from
      children not included in the previous ESCF study, we confirmed that these four
      characteristics were significantly associated with the likelihood of physicians
      prescribing antibiotics to treat a pulmonary exacerbation. The number of these
      characteristics present at a single clinic visit before age 6 predicted
      hospitalization rate over the next year, the weight-for-age z-score, and the
      forced expiratory volume in 1 sec (FEV1) percent predicted at age 7. Treatment
      with antibiotics was associated with a greater decrease in the proportion of
      children with crackles, cough, and Pseudomonas aeruginosa at a follow-up visit
      within 6 months. CONCLUSIONS: New crackles, increased cough, increased sputum,
      and decline in weight percentile at a single clinic visit increase the risk of
      future malnutrition, hospitalization, and airflow obstruction in young children
      with CF. Treatment with antibiotics mitigates some of these signs and symptoms by
      the first follow-up visit. The presence of these four characteristic signs and
      symptoms is useful to define pulmonary exacerbations in young children with CF
      that respond to antibiotic treatment in the short-term and influence long-term
      prognosis.

PMID- 22949089
TI  - Transcranial current brain stimulation (tCS): models and technologies.
AB  - In this paper, we provide a broad overview of models and technologies pertaining
      to transcranial current brain stimulation (tCS), a family of related noninvasive
      techniques including direct current (tDCS), alternating current (tACS), and
      random noise current stimulation (tRNS). These techniques are based on the
      delivery of weak currents through the scalp (with electrode current intensity to
      area ratios of about 0.3-5 A/m2) at low frequencies (typically < 1 kHz) resulting
      in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here
      we review the biophysics and simulation of noninvasive, current-controlled
      generation of electric fields in the human brain and the models for the
      interaction of these electric fields with neurons, including a survey of in vitro
      and in vivo related studies. Finally, we outline directions for future
      fundamental and technological research.

PMID- 22949090
TI  - AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal
      function.
AB  - The renin-angiotensin system (RAS) is a coordinated hormonal cascade intimately
      involved in cardiovascular and renal control and blood pressure regulation.
      Angiotensin II (Ang II), the major RAS effector peptide, binds two distinct
      receptors, the angiotensin type-1 receptor (AT(1)R) and the angiotensin type-2
      (AT(2)R) receptor. The vast majority of the physiological actions of Ang II,
      almost all of them detrimental, are mediated by AT(1)Rs. In contrast, AT(2)Rs
      negatively modulate the actions of AT(1)Rs under the majority of circumstances
      and generally possess beneficial effects. AT(2)Rs induce vasodilation in both
      resistance and capacitance vessels, mediating natriuresis directly and via
      interactions with dopamine D1 receptors in the renal proximal tubule. AT(2)Rs
      inhibit renin biosynthesis and secretion and protect the kidneys from
      inflammation and ischemic injury. Our understanding of the exact role of AT(2)Rs
      in physiology and pathophysiology continues to expand; the purpose of this review
      is to provide an up-to-date summary of the functional role of AT(2)Rs at the
      organ, tissue, cellular, and subcellular levels with emphasis on the vascular and
      renal actions that bear on blood pressure regulation and hypertension.

PMID- 22949091
TI  - Poor health, unhealthy behaviors, and unfavorable work characteristics influence
      pathways of exit from paid employment among older workers in Europe: a four year
      follow-up study.
AB  - OBJECTIVES: The aim of this study was to get insight into the role of poor
      health, unhealthy behaviors, and unfavorable work characteristics on exit from
      paid employment due to disability pension, unemployment, and early retirement
      among older workers. METHODS: Respondents of the longitudinal Survey of Health,
      Ageing, and Retirement in Europe (SHARE) in 11 European countries were selected
      when (i) aged between 50 years and the country-specific retirement age, (ii) in
      paid employment at baseline, and (iii) having information on employment status
      during the 4-year follow-up period (N=4923). Self-perceived health, health
      behaviors, and physical and psychosocial work characteristics were measured by
      interview at baseline. Employment status was derived from follow-up interviews
      after two and four years. Cox proportional hazards regression analyses were used
      to identify determinants of unemployment, disability pension, and early
      retirement. RESULTS: Poor health was a risk factor for disability pension [hazard
      ratio (HR) 3.90, 95% confidence interval (95% CI) 2.51-6.05], and a lack of
      physical activity was a risk factor for disability pension (HR 3.05, 95% CI 1.68
      5.55) and unemployment (HR 1.84, 95% CI 1.13-3.01). A lack of job control was a
      risk factor for disability pension, unemployment, and early retirement (HR 1.30
      1.77). CONCLUSIONS: Poor health, a lack of physical activity, and a lack of job
      control played a role in exit from paid employment, but their relative importance
      differed by pathway of labor force exit. Primary preventive interventions
      focusing on promoting physical activity as well as increasing job control may
      contribute to reducing premature exit from paid employment.

PMID- 22949093
TI  - Pseudorotaxane based on tetraazamacrocyclic copper complex and dibenzocrown
      ether.
AB  - Host-guest interactions between two electron-rich dibenzocrown ethers and
      electron deficient macrocyclic copper(II) tetraimine complexes lead to the
      formation of pseudorotaxane in solution. The interactions are enhanced with the
      copper(III) complex compared to that of the copper(II) form as shown by the
      electrochemical studies. The larger--30-membered dibenzocrown donor interacted
      with the copper complex stronger than the smaller ones as revealed by NMR and
      electrochemical methods. The thiolated form of the copper(II) tetraimine complex
      was self-assembled at the gold electrode forming an electroactive monolayer able
      to interact with the crown ether in the solution. These donor-acceptor
      interactions lead to an increase of the barrier properties of the layer and
      decreased the electron transfer rate between the copper centre and the gold
      electrode surface as proved by the voltammetric data.

PMID- 22949092
TI  - Genistein inhibits Abeta25-35 -induced neurotoxicity in PC12 cells via PKC
      signaling pathway.
AB  - Protein kinase C (PKC) signaling pathway is recognized as an important molecular
      mechanism of Alzheimer's disease (AD) in the regulation of neuronal plasticity
      and survival. Genistein, the most active molecule of soy isoflavones, exerts
      neuroprotective roles in AD. However, the detailed mechanism has not been fully
      understood yet. The present study aimed to investigate whether the
      neuroprotective effects of genistein against amyloid beta (Abeta)-induced
      toxicity in cultured rat pheochromocytoma (PC12) cells is involved in PKC
      signaling pathway. PC12 cells were pretreated with genistein for 2 h following
      incubation with Abeta(25-35) for additional 24 h. Cell viability was assessed by
      MTT. Hoechst33342/PI staining was applied to determine the apoptotic cells. PKC
      activity, intracellular calcium level and caspase-3 activity were analyzed by
      assay kits. The results showed that pretreatment with genistein significantly
      increased cell viability and PKC activity, decreased the levels of intracellular
      calcium, attenuated Hoechst/PI staining and blocked caspase-3 activity in
      Abeta(25-35)-treated PC12 cells. Pretreatment of Myr, a general PKC inhibitor,
      significantly attenuated the neuroprotective effect of genistein against Abeta(25
      35)-treated PC12 cells. The present study indicates that PKC signaling pathway is
      involved in the neuroprotective action of genistein against Abeta(25-35)-induced
      toxicity in PC12 cells.

PMID- 22949094
TI  - Angiotensin-converting enzyme inhibitor use and pneumonia risk in community
      dwelling older adults: results from a population-based case-control study.
AB  - PURPOSE: To test whether angiotensin-converting enzyme (ACE) inhibitor use is
      associated with decreased risk of community-acquired pneumonia in older adults.
      METHODS: We analyzed data from a nested case-control study of community-dwelling,
      immunocompetent adults aged 65-94 within an integrated healthcare delivery
      system. Cases of ambulatory and hospitalized pneumonia from 2000 to 2003 were
      identified from International Classification of Disease, version 9, codes and
      validated using medical record review. Controls were matched to cases by age,
      sex, and calendar year. Using health plan pharmacy data, we defined current use
      as filling >=2 prescriptions during the 180 days prior to the case's diagnosis
      date. We calculated standardized doses per day using World Health Organization
      defined daily doses. Multivariable conditional logistic regression estimated
      adjusted odds ratios (ORs) for pneumonia in relation to ACE inhibitor use,
      adjusting for comorbidity, functional and cognitive status, and other covariates
      from medical record review and pharmacy data. RESULTS: Current use of ACE
      inhibitors was seen in 23% (242/1039) of cases and 21% (433/2022) of controls.
      Lisinopril accounted for 95% of prescriptions. The OR for pneumonia comparing
      current use to no current use was 0.99 (95% confidence interval [CI] 0.83-1.19).
      The OR for use of more than two standardized daily doses per day was 1.39 (95% CI
      0.93-2.06) compared to no current use. CONCLUSIONS: ACE inhibitor use is not
      associated with reduced pneumonia risk in community-dwelling older adults.

PMID- 22949095
TI  - Putative biological mechanisms of efficiency of substrate reduction therapies for
      mucopolysaccharidoses.
AB  - Mucopolysaccharidoses (MPS) are inherited metabolic diseases caused by mutations
      in genes coding for lysosomal enzymes involved in the degradation of
      glycosaminoglycans (GAGs). Dysfunction of any of these enzymes results in the
      accumulation of GAGs, which leads to severe clinical symptoms and significantly
      shortened life span. Several kinds of therapies have been proposed to treat MPS,
      including bone marrow or stem cell transplantation, enzyme replacement therapy,
      and gene therapy. Another option is substrate reduction therapy (SRT), in which
      synthesis of GAGs is inhibited. Recent studies employing in vitro and animal
      models suggested that this therapy may be efficient in decreasing levels of GAGs
      in MPS cells, including those bearing two null alleles of the affected gene.
      Results of behavioral tests in animals as well as some preliminary clinical
      observations with pediatric patients corroborated the suggestions about possible
      efficacy of SRT in MPS treatment, including brain functions. Efficient reduction
      of GAG levels in MPS cells homozygous for null mutations may be intriguing in the
      commonly accepted scheme of SRT mode of action. In this paper, we propose an
      explanation of this phenomenon, based on already known facts. Thus, we suggest
      that SRT may lead to reduction of GAG levels in MPS cells due to inhibition of
      efficiency of GAG synthesis combined with (a) any readthrough of the stop codon,
      (b) dilution of already accumulated GAGs due to cell growth followed by cell
      divisions, and (c) action of endoglycosidases degrading GAGs, e.g., heparanase,
      in combination with functional GAG-specific hydrolases.

PMID- 22949096
TI  - In vitro invasion and survival of Porphyromonas gingivalis in gingival
      fibroblasts; role of the capsule.
AB  - Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium involved in
      periodontitis and peri-implantitis that can invade and survive inside host cells
      in vitro. P. gingivalis can invade human gingival fibroblasts (GF), but no data
      are available about the role of P. gingivalis' capsule in GF invasion. In the
      current study, we aimed to determine the ability of three strains of P.
      gingivalis (encapsulated wild type W83, non-encapsulated HG91 and the non
      encapsulated insertional isogenic knockout mutant of W83, DeltaEpsC) to invade GF
      and the ability of internalized P. gingivalis to survive in vitro antibiotic
      treatment. The ability of P. gingivalis strains to invade GF was tested using an
      antibiotic protection assay at multiplicity of infection (MOI) 100 and 1000. The
      survival of internalized P. gingivalis cells was further analyzed by subsequent
      in vitro treatment with either metronidazole or amoxicillin alone or a
      combination of metronidazole and amoxicillin and anaerobic culture viability
      counts. All strains of P. gingivalis used in this study were able to invade GFs.
      The non-encapsulated mutant of W83 (DeltaEpsC mutant) was significantly more
      invasive than the wild type W83 at MOI 100 (p value 0.025) and MOI 1000 (p value
      0.038). Furthermore, internalized P. gingivalis was able to resist in vitro
      antibiotic treatment. As demonstrated by the differences in invasion efficiencies
      of P. gingivalis strain W83 and its isogenic mutant DeltaEpsC, the capsule of P.
      gingivalis makes it less efficient in invading gingival fibroblasts. Moreover,
      internalized P. gingivalis can survive antibiotic treatment in vitro.

PMID- 22949097
TI  - Normal forms of spiking neural P systems with anti-spikes.
AB  - Spiking neural P systems with anti-spikes (ASN P systems, for short) are a
      variant of spiking neural P systems, which were inspired by inhibitory
      impulses/spikes or inhibitory synapses. In this work, we consider normal forms of
      ASN P systems. Specifically, we prove that ASN P systems with pure spiking rules
      of categories (a, a) and (a, (a)) without forgetting rules are universal as
      number generating devices. In an ASN P system with spiking rules of categories
      (a, (a)) and ((a), a) without forgetting rules, the neurons change spikes to anti
      spikes or change anti-spikes to spikes; such systems are proved to be universal.
      We also prove that ASN P systems with inhibitory synapses using pure spiking
      rules of category (a, a) and forgetting rules are universal. These results answer
      an open problem and improve a corresponding result from [IJCCC, IV(3), 2009, 273
      282].

PMID- 22949098
TI  - Hybrid nanomaterial for stabilizing the antibiofilm activity of Eugenia
      carryophyllata essential oil.
AB  - The aim of the present study was to demonstrate that   Fe(3)O(4)/oleic acid 
      core/shell nanostructures could be used as systems for stabilizing the Eugenia
      carryophyllata essential oil (EO) on catheter surface pellicles, in order to
      improve their resistance to fungal colonization. EO microwave assisted extraction
      was performed in a Neo-Clevenger (related) device and its chemical composition
      was settled by GC-MS analysis.  Fe(3)O(4)/oleic acid-core/shell nanoparticles
      (NP) were obtained by a precipitation method under microwave condition. High
      resolution transmission electron microscopy (HR-TEM) was used as a primary
      characterization method. The NPs were processed to achieve a core/shell/EO coated
      shell nanosystem further used for coating the inner surface of central venous
      catheter samples. The tested fungal strains have been recently isolated from
      different clinical specimens. The biofilm architecture was assessed by confocal
      laser scanning microscopy (CLSM). Our results claim the usage of hybrid
      nanomaterial (core/shell/coated-shell) for the stabilization of E. carryophyllata
      EO, which prevented or inhibited the fungal biofilm development on the
      functionalized catheter, highlighting the opportunity of using these nanosystems
      to obtain improved, anti-biofilm coatings for biomedical applications.

PMID- 22949099
TI  - Intraductal carcinoma of the prostate: precursor or aggressive phenotype of
      prostate cancer?
AB  - BACKGROUND: Although the term "intraductal carcinoma of the prostate" (IDC-P) was
      introduced almost 40 years ago, there is still the lack of appreciation that this
      entity represents a clinically aggressive disease that continues to be
      misreported under the diagnostic category of high grade prostatic intraepithelial
      neoplasia (HGPIN). METHODS: Recent data obtained from histological, molecular,
      and clinical studies were reviewed to demonstrate that IDC-P significantly
      differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and
      therapy of prostate cancer (PCa). RESULTS: HGPIN is the only accepted precursor
      of PCa. Its diagnosis in prostate biopsies has no prognostic implications, and
      does not dictate therapeutic decisions. By contrast, IDC-P correlates with a
      worse pathological and clinical outcome. IDC-P differs from HGPIN by distinct
      histological and molecular features. Recent clinical studies report that IDC-P is
      associated with neoadjuvant androgen deprivation therapy (ADT) and, chemotherapy
      (CT) failure as well as early disease recurrence after external beam radiation.
      Finally, IDC-P is associated with TMPRSS2-ERG gene fusion, which was reported to
      be regulated by estrogens and their receptors. CONCLUSIONS: IDC-P is an
      aggressive phenotype of prostate cancer and predicts poor response to ADT, CT,
      and external beam radiation. IDC-P should be separated from HGPIN and should be
      reported in prostate biopsies and prostatectomy specimens.

PMID- 22949100
TI  - Comparison of Foxp3+ regulatory T cells and CD163+ macrophages in invasive and
      non-invasive extramammary Paget's disease.
AB  - Regulatory T cells (Tregs), identified by the expression of CD4, CD25 and Foxp3,
      together with immunosuppressive macrophages, such as CD163+ M2 macrophages, are
      involved in maintaining peripheral tolerance. The aim of this study was to
      elucidate the involvement of Tregs and CD163+ macrophages in invasive and non
      invasive extramammary Paget's disease. The presence of CD4+CD25+Foxp3+ Tregs,
      CD163+ M2 macrophages and matrix metalloproteinase-9+ cells was examined
      immunohistologically in fixed sections of lesional skin from 10 patients with non
      invasive extramammary Paget's disease and 7 patients with invasive extramammary
      Paget's disease. Fewer CD4+CD25+Foxp3+ Tregs were observed in non-invasive
      extramammary Paget's disease than in invasive extramammary Paget's disease. In
      contrast, higher numbers of CD163+ macrophages and metalloproteinase-9+ cells
      were detected only in invasive extramammary Paget's disease. These findings
      suggest that the induction of immunosuppressive cells in extramammary Paget's
      disease differs according to the tumour stage.

PMID- 22949101
TI  - Alcohol and pregnancy: do abstinence policies have unintended consequences?
AB  - Most policies and guidelines recommend that women abstain from alcohol during
      pregnancy. This can be difficult to achieve in developed nations where the
      majority of women consume alcohol and almost half of pregnancies are unplanned,
      leading to many pregnancies being exposed to alcohol prior to pregnancy
      awareness. Concerns have been raised that abstinence policies may lead women in
      this situation to terminate their pregnancy out of fear that they have harmed
      their baby; however, the evidence is limited. A recent study found that while few
      women reported alcohol as the reason for seeking an abortion, in almost all cases
      where alcohol was the reason, the women were either binge drinking or reported
      alcohol-related problems and the pregnancy was unplanned.

PMID- 22949102
TI  - A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from
      subgroup analyses.
AB  - AIMS: To quantify the magnitude of the association between alcohol and oral and
      pharyngeal cancer (OPC) by sex, smoking habits, type of alcoholic beverage and
      other factors. METHODS: We combined findings from all case-control and cohort
      studies published until September 2010 and present in this article the results
      classified by these factors, using a meta-analytic approach. Summary relative
      risks (RRs) were obtained using random-effects models; heterogeneity was assessed
      using the chi(2) test. RESULTS: The association between alcohol and OPC risk was
      similar in men and women, with similar dose-response relationships. No notable
      differences were found with respect to geographic area and other factors, both
      for drinking overall and heavy (>=4 drinks/day) drinking. Among never/non-current
      smokers, the pooled RRs were 1.32 (95% confidence interval, CI, 1.05-1.67) for
      drinking, and 2.54 (95% CI, 1.80-3.58) for heavy drinking. The corresponding RRs
      in smokers were 2.92 (95% CI, 2.31-3.70) and 6.32 (95% CI, 5.05-7.90). The pooled
      RRs for any drinking irrespective of smoking were 2.12 (95% CI, 1.37-3.29) for
      wine-, 2.43 (95% CI, 1.92-3.07) for beer- and 2.30 (95% CI, 1.78-2.98) for
      spirits-only drinking. The corresponding RRs for heavy drinking were 4.92 (95%
      CI, 2.80-8.65), 4.20 (95% CI, 1.43-12.38) and 5.20 (95% CI, 2.77-9.78).
      CONCLUSION: The alcohol-related RRs are similar with respect to sex, geographic
      area and type of alcoholic beverage. The association between alcohol and OPC is
      stronger in smokers than in non-smokers.

PMID- 22949103
TI  - Dynamic transcription factor activity profiling in 2D and 3D cell cultures.
AB  - Live-cell assays to measure cellular function performed within 3D cultures have
      the potential to elucidate the underlying processes behind disease progression
      and tissue formation. Cells cultured in 3D interact and remodel their
      microenvironment and can develop into complex structures. We have developed a
      transcription factor (TF) activity array that uses bioluminescence imaging (BLI)
      of lentiviral delivered luminescent reporter constructs that allows for the non
      invasive imaging of TF activity in both 2D and 3D culture. Imaging can be applied
      repeatedly throughout culture to capture dynamic TF activity, though appropriate
      normalization is necessary. We investigated in-well normalization using Gaussia
      or Renilla luciferase, and external well normalization using firefly luciferase.
      Gaussia and Renilla luciferase were each unable to provide consistent
      normalization for long-term measurement of TF activity. However, external well
      normalization provided low variability and accounted for changes in cellular
      dynamics. Using external normalization, dynamic TF activities were quantified for
      five TFs. The array captured expected changes in TF activity to stimuli, however
      the array also provided dynamic profiles within 2D and 3D that have not been
      previously characterized. The development of the technology to dynamically track
      TF activity within cells cultured in both 2D and 3D can provide greater
      understanding of complex cellular processes.

PMID- 22949104
TI  - Anemia, age, desaturation, and impaired neurocognition in sickle cell anemia.

PMID- 22949106
TI  - Fructose and risk of cardiometabolic disease.
AB  - Fructose and glucose in soft drinks and fruit drinks account for just under 50 %
      of added sugars. Soft drinks intake has risen five-fold between 1950 and 2000,
      and this increase in intake of simple sugars has raised health concerns. The
      risks of cardiovascular disease, obesity and the metabolic syndrome have all been
      related to consumption of sugar-sweetened beverages in several, but not all meta
      analyses. Fructose and sugar-sweetened beverages have also been related to the
      risk of gout in men, and to non-alcoholic fatty liver disease. Studies show that
      the calories in sugar-sweetened beverages do not produce an adequate reduction in
      the intake of other foods, leading to increased caloric intake. Plasma
      triglycerides are increased by sugar-sweetened beverages, and this increase
      appears to be due to fructose, rather than to glucose in sugar. Several 10-week
      to 26-week randomized trials of sugar-containing soft drinks show increases in
      triglycerides, body weight, and visceral adipose tissue; there were also
      increases in muscle fat and liver fat, which might lead to non-alcoholic-fatty
      liver disease.

PMID- 22949105
TI  - Nanog reverses the effects of organismal aging on mesenchymal stem cell
      proliferation and myogenic differentiation potential.
AB  - Although the therapeutic potential of mesenchymal stem cells (MSCs) is widely
      accepted, loss of cell function due to donor aging or culture senescence are
      major limiting factors hampering their clinical application. Our laboratory
      recently showed that MSCs originating from older donors suffer from limited
      proliferative capacity and significantly reduced myogenic differentiation
      potential. This is a major concern, as the patients most likely to suffer from
      cardiovascular disease are elderly. Here we tested the hypothesis that a single
      pluripotency-associated transcription factor, namely Nanog, may reverse the
      proliferation and differentiation potential of bone marrow-derived MSC (BM-MSC)
      from adult donors. Microarray analysis showed that adult (a)BM-MSC expressing
      Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly
      upregulated genes involved in cell cycle, DNA replication, and DNA damage repair
      and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably,
      Nanog reversed the myogenic differentiation potential and restored the
      contractile function of aBM-MSC to a similar level as that of neonatal (n)BM-MSC.
      The effect of Nanog on contractility was mediated--at least in part--through
      activation of the TGF-beta pathway by diffusible factors secreted in the
      conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that
      Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby
      increasing the potential of MSC from aged donors for cellular therapy and tissue
      regeneration.

PMID- 22949107
TI  - Phototherapeutic hardening modulates systemic cytokine levels in patients with
      polymorphic light eruption.
AB  - The etiopathogenesis of polymorphic light eruption (PLE) has been linked to
      impaired UV-immunosuppression, Langerhans cell (LC) retention, and an absence of
      neutrophil infiltration into UV-exposed PLE skin. We have previously shown that
      photohardening restores the impaired neutrophil responsiveness to the
      chemoattractants leucotriene B4 and formyl-methionyl-leucyl-phenylalanin in PLE
      patients. The aim of this study was to investigate whether photohardening
      modulates baseline chemokine and cytokine levels which would alter
      chemoresponsiveness and hence immune function in PLE patients. Sixteen PLE
      patients received photohardening therapy for 4-9 weeks by 311 nm UVB. Plasma
      samples were taken both before and within 48 h of the penultimate
      phototherapeutic exposure. Plasma from these 16 patients, 8 non-irradiated PLE
      patients, and 14 control subjects was analyzed for IL-1beta, CXCL8 (IL-8), IL-10,
      IL-17, TNF, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), and CCL22 (MDC). These
      cytokines and chemokines were measured in early spring (March to April) and again
      in late spring (April to June). PLE patients had a significantly elevated level
      of CCL11 (p = 0.003) and IL-1beta (p = 0.002) in early spring (before
      phototherapy). In late spring, after phototherapy, PLE patients had significantly
      elevated CCL2 (p = 0.002) and TNF (p = 0.002) but a trend for lowered plasma
      levels of CXCL8 (p = 0.021). When comparing the cytokine shifts from early to
      late spring, while healthy controls and non-UV-irradiated PLE patients showed an
      increase, PLE patients undergoing photohardening exhibited a trend for decrease
      in IL-1beta (p = 0.012). Taken together, our results indicate that photohardening
      may alter the complex cytokine milieu in PLE, in particular via IL-1beta, helping
      to normalise the pathophysiologic response to subsequent UV exposure.

PMID- 22949108
TI  - Dimers, oligomers, everywhere.
AB  - The specific self-association of proteins to form homodimers and higher order
      oligomers is an extremely common event in biological systems. In this chapter we
      review the prevalence of protein oligomerization and discuss the likely origins
      of this phenomenon. We also outline many of the functional advantages conferred
      by the dimerization or oligomerization of a wide range of different proteins and
      in a variety of biological roles, that are likely to have placed a selective
      pressure on biological systems to evolve and maintain
      homodimerization/oligomerization interfaces.

PMID- 22949109
TI  - The detection and quantitation of protein oligomerization.
AB  - There are many different techniques available to biologists and biochemists that
      can be used to detect and characterize the self-association of proteins. Each
      technique has strengths and weaknesses and it is often useful to combine several
      approaches to maximize the former and minimize the latter. Here we review a range
      of methodologies that identify protein self-association and/or allow the
      stoichiometry and affinity of the interaction to be determined, placing an
      emphasis on what type of information can be obtained and outlining the advantages
      and disadvantages involved. In general, in vitro biophysical techniques, such as
      size exclusion chromatography, analytical ultracentrifugation, scattering
      techniques, NMR spectroscopy, isothermal titration calorimetry, fluorescence
      anisotropy and mass spectrometry, provide information on stoichiometry and/or
      binding affinities. Other approaches such as cross-linking, fluorescence methods
      (e.g., fluorescence correlation spectroscopy, FCS; Forster resonance energy
      transfer, FRET; fluorescence recovery after photobleaching, FRAP; and proximity
      imaging, PRIM) and complementation approaches (e.g., yeast two hybrid assays and
      bimolecular fluorescence complementation, BiFC) can be used to detect protein
      self-association in a cellular context.

PMID- 22949110
TI  - Computational and structural characterisation of protein associations.
AB  - Protein-protein associations represent the building blocks of biological systems.
      The classification of different types of protein association is fundamental to an
      understanding of the interactions they exhibit. A protein association can be
      classified as homo- (identical components) or hetero- (non-identical components)
      and in addition permanent (components only exist and function in an associated
      state) or transient (components exist independently but interact for a limited
      time to carry out a specific function). A large number of studies have analysed
      the physical and chemical characteristics of protein-protein interactions using
      three-dimensional structures derived from X-ray crystallography. This chapter
      summarises the major conclusions of these studies, focusing on amino acid
      preferences and secondary structure packing at interfaces: hydration, hydrophobic
      and electrostatic effects, conformational changes and evolutionary conservation.
      The studies highlight differences between the interaction sites and the rest of
      the protein surface and between different classes of protein association. Common
      themes in the interfaces of protein associations are also revealed including
      shape complementarity, the presence of water molecules, a high percentage of
      arginine residues, intermolecular hydrogen bonds and an energy of association
      comprising hydrophobic and electrostatic effects. These studies also emphasise
      how the relative importance of such characteristics is dependant upon the class
      of protein association, with permanent associations generally displaying
      different characteristics to transient associations.

PMID- 22949111
TI  - Death by caspase dimerization.
AB  - Controlled cell death, or apoptosis, occurs in response to many different
      environmental stimuli. The apoptotic cascade that occurs within the cell in
      response to these cues leads to morphological and biochemical changes that
      trigger the dismantling and packaging of the cell. Caspases are a family of
      cysteine-dependent aspartate-directed proteases that play an integral role in the
      cascade that leads to apoptosis. Caspases are grouped as either initiators or
      effectors of apoptosis, depending on where they enter the cell death process.
      Prior to activation, initiator caspases are present as monomers that must
      dimerize for full activation whereas effector caspases are present as dimeric
      zymogens that must be processed for full activation. The stability of the dimer
      may be due predominately to the interactions in the dimer interface as each
      caspase has unique properties in this region that lend to its specific mode of
      activation. Moreover, dimerization is responsible for active site formation
      because both monomers contribute residues that enable the formation of a fully
      functional active site. Overall, dimerization plays a key role in the ability of
      caspases to form fully functional proteases.

PMID- 22949112
TI  - The relationship between oligomeric state and protein function.
AB  - The reason that many proteins adopt a particular oligomeric form is far from
      obvious. In this chapter, we discuss potential advantages of proteins self
      assembling into specific quaternary structures. A number of case studies are
      presented in which wild-type proteins have been mutated to generate variants of
      lower oligomeric order and the impact on the resulting proteins, in terms of both
      specific function and generic stability, are discussed. Drawing on these case
      studies, some general design principles for quaternary structure engineering are
      put forward to facilitate these experiments on a wider range of systems. It is
      clear that the advantages afforded by quaternary structure vary from protein to
      protein; however, some general trends are starting to emerge.

PMID- 22949113
TI  - Oligonucleotide binding proteins: the occurrence of dimer and multimer formation.
AB  - Protein dimers and multimers are often employed by nature for DNA and RNA
      handling and formation of specific, high-affinity protein-oligonucleotide
      complexes. The repeating structure of dsDNA lends itself to recognition by
      multimeric protein complexes that can assemble about the helical structure. In
      the cases of both DNA and RNA, specific recognition of nucleotide sequences can
      be achieved by multidomain proteins or protein multimers. Furthermore large
      multimeric assemblies are utilised for the stable formation of structures such as
      rings and filaments. Also, the assembly of multimeric structures by
      interchangeable subunits can add layers of regulation and increase functional
      complexity. Thus there appear to be many advantages to oligonucleotide
      interactions that are conferred by dimerisation or multimerisation.

PMID- 22949114
TI  - Homo- and heterodimerization in transcriptional regulation.
AB  - Eukaryotic transcription factors bind DNA and typically serve to localize large
      multiprotein complexes to particular genes to up- or downregulate transcription,
      thereby coordinating cellular responses to a variety of signals. Different
      combinations of transcription factors within DNA-binding multiprotein complexes
      allow individual proteins to partake in multiple different regulatory pathways.
      Many transcription factors can form homo- and heterodimers (or oligomers) with
      different partners, thus modulating DNA-binding specificity and affinity and/or
      the recruitment of different binding partners. This chapter reviews several of
      the mechanisms by which the homo- and heterodimerization of transcription factors
      contributes to transcriptional regulation.

PMID- 22949115
TI  - Oligomerization at the membrane: potassium channel structure and function.
AB  - Cell membranes present a naturally impervious barrier to aqueous solutes, such
      that the physiochemical environment on either side of the lipid bilayer can
      substantially differ. Integral membrane proteins are embedded in this
      heterogeneous lipid environment, wherein the juxtaposition of apolar and polar
      molecular surfaces defines factors such as transverse orientation, the surface
      area available for oligomerisation and the symmetry of resultant assemblies. This
      chapter focuses on potassium channels -representative molecular pores that play a
      critical role in electrical signalling by enabling selective transport of K(+)
      ions across cell membranes. Oligomerization is central to K(+) channel action;
      individual subunits are nonfunctional and conduction, selectivity and gating
      involve manipulation of the common subunit interface of the tetramer. Regulation
      of channel activity can be viewed from the perspective that the pore of K(+)
      channels has coopted other proteins, utilizing a process of hetero
      oligomerisation to absorb new functions that both enable the pore to respond to
      extrinsic signals and provide an electrical signature.

PMID- 22949116
TI  - Implications of 3D domain swapping for protein folding, misfolding and function.
AB  - Three-dimensional domain swapping is the process by which two identical protein
      chains exchange a part of their structure to form an intertwined dimer or higher
      order oligomer. The phenomenon has been observed in the crystal structures of a
      range of different proteins. In this chapter we review the experiments that have
      been performed in order to understand the sequence and structural determinants of
      domain-swapping and these show how the general principles obtained can be used to
      engineer proteins to domain swap. We discuss the role of domain swapping in
      regulating protein function and as one possible mechanism of protein misfolding
      that can lead to aggregation and disease. We also review a number of interesting
      pathways of macromolecular assembly involving beta-strand insertion or
      complementation that are related to the domain-swapping phenomenon.

PMID- 22949117
TI  - From artificial antibodies to nanosprings: the biophysical properties of repeat
      proteins.
AB  - In this chapter we review recent studies of repeat proteins, a class of proteins
      consisting of tandem arrays of small structural motifs that stack approximately
      linearly to produce elongated structures. We discuss the observation that,
      despite lacking the long-range tertiary interactions that are thought to be the
      hallmark of globular protein stability, repeat proteins can be as stable and as
      co-orperatively folded as their globular counterparts. The symmetry inherent in
      the structures of repeat arrays, however, means there can be many partly folded
      species (whether it be intermediates or transition states) that have similar
      stabilities. Consequently they do have distinct folding properties compared with
      globular proteins and these are manifest in their behaviour both at equilibrium
      and under kinetic conditions. Thus, when studying repeat proteins one appears to
      be probing a moving target: a relatively small perturbation, by mutation for
      example, can result in a shift to a different intermediate or transition state.
      The growing literature on these proteins illustrates how their modular
      architecture can be adapted to a remarkable array of biological and physical
      roles, both in vivo and in vitro. Further, their simple architecture makes them
      uniquely amenable to redesign-of their stability, folding and function-promising
      exciting possibilities for future research.

PMID- 22949118
TI  - Metastatic melanoma.

PMID- 22949119
TI  - Pericardial cyst: a benign anomaly.

PMID- 22949120
TI  - Unusual cause of pericardial effusion.
AB  - A 65-year-old Egyptian lady suffering from non-alcoholic liver cirrhosis was
      referred to our unit for evaluation of a massive pericardial effusion. Few weeks
      before presentation, she suffered from progressive abdominal distention and
      dyspnoea. She denied fever, rigors or other cardiorespiratory symptoms.
      Examination revealed shrunken liver, spleenomegaly and ascites. Chest was clear
      to auscultation and heart sounds were distant. Chest radiograph showed
      cardiomegaly and clear lung fields. Abdominal ultrasound confirmed the results of
      abdominal examination. Transthoracic echocardiogram (TTE) revealed a massive
      pericardial effusion (PEF) and rheumatic mitral stenosis. Chest tomography showed
      PEF and clear lung fields. One litre of exudate was removed via TTE-guided needle
      pericardiocentesis. A pericardio-peritoneal shunt was suspected, which was
      confirmed via a radioisotopic study. This case is among very few cases that
      reported PEF in a cirrhotic ascetic patient secondary to a radio-isotopically
      confirmed pericardio-peritoneal shunt in the literature.

PMID- 22949121
TI  - Optimizing nanovial outlet designs for improved solid-phase extraction in the
      integrated selective enrichment target--ISET.
AB  - The integrated selective enrichment target is a microfluidic platform for SPE
      sample preparation with integrated nanocolumns, which simultaneously offers
      direct MALDI MS read-out. Here, we present a study on the importance of different
      nanocolumn outlet hole geometries and hole areas in relation to MS signal
      intensity and reproducibility. A design solution that provides the flow
      characteristics required for robust sample preparation using automated liquid
      handling is reported.

PMID- 22949122
TI  - Assessment of preemptive analgesia with ibuprofen coadministered or not with
      dexamethasone in third molar surgery: a randomized double-blind controlled
      clinical trial.
AB  - INTRODUCTION: There is no conclusive evidence from clinical trial studies
      regarding preemptive analgesic interventions. Clinical trials are necessary to
      evaluate the efficacy of preemptive analgesic interventions already demonstrated
      in animal studies. Thus, it is necessary to evaluate the analgesic effect of
      preoperative administration of ibuprofen alone or coadministered with
      dexamethasone after third molar surgery. MATERIAL AND METHODS: A randomized,
      double-blind, and controlled clinical trial was conducted with 94 bilateral
      symmetrical third molar surgeries. Preemptive analgesic medication was randomly
      defined: ibuprofen or placebo and ibuprofen + dexamethasone or placebo was
      administered to patients who served as their own control (split mouth). The
      variables analyzed were postoperative pain through visual analog scale (VAS),
      total number of rescue analgesic (TNRA), and patient satisfaction. Data were
      analyzed with the Mann-Whitney test. RESULTS: There was no significant difference
      (p > 0.05) between ibuprofen and placebo for postoperative pain (VAS) and TNRA.
      Patients consumed less analgesics (TNRA) for dexamethasone + ibuprofen (p < 0.05)
      and felt more comfortable in the postoperative period after surgery (p < 0.05).
      DISCUSSION: The preemptive analgesia with ibuprofen was insufficient to inhibit
      central sensitization, whereas its association with dexamethasone was more
      effective in preventing pain in third molar surgery.

PMID- 22949123
TI  - Influence of computer navigation on TKA revision rates.
AB  - PURPOSE: We performed this study to determine whether the use of imageless
      navigation reduces revision rates after total knee arthroplasty (TKA). METHODS:
      Data of 1,121 consecutive primary TKA with a follow-up of one to six years were
      retrospectively analysed. Following the conversion of the standard technique from
      conventional to navigated procedures, these data included the last 342
      conventional and first 779 navigated procedures performed in our clinic.
      Demographic and perioperative covariates were recorded. All patients were asked
      by post to report instances of revisions. RESULTS: Data of 1,054 patients (94 %)
      were complete. Mean follow-up was 3.9 years for conventional and 2.4 years for
      navigated operations. Cumulative revision rate averaged 4.7 % for conventional
      and 2.3 % for navigated procedures. Cox's proportional hazard model was used to
      assess the effect of covariates on survival, resulting in significantly lower
      revision rates for older patients (p < 0.001) and for the navigated technique (p
      = 0.012). The reduced revision rate for navigated operations was mainly caused by
      a significantly reduced rate of aseptic implant loosening (1.9 % vs. 0.1 %, p =
      0.024). CONCLUSIONS: Our study showed lower revision rates when computer
      navigation was used. However, due to the retrospective uncontrolled design,
      further prospective trials will be necessary to further evaluate this effect.

PMID- 22949124
TI  - New method for measuring acetabular component positioning with EOS imaging:
      feasibility study on dry bone.
AB  - PURPOSE: Malposition of the acetabular cup is the most common cause of total hip
      arthroplasty (THA) dislocation. The position of a total hip implant is usually
      analysed on computed tomography (CT) scan. We aim to prove it is possible to
      measure, with good accuracy, the position of an acetabular cup using the low-dose
      irradiation (EOS) imaging. MATERIAL AND METHODS: We implanted an acetabular cup
      in a pelvic dry bone and measured cup anteversion and inclination with
      scanography. We performed 14 series of EOS acquisitions with different
      inclination, rotation and pelvic tilt, which were analysed by five observers. Two
      observers repeated angle measurements. We then calculated measurement inter- and
      intrareproducibility and accuracy. RESULTS: Using a confidence interval (CI) of
      95 %, inter- and intra-observer reproducibility were +/-1.6, and +/-1.4 degrees ,
      respectively, for cup inclination; accuracy in comparison with CT was +/-2.6
      degrees . Using a 95 % CI, inter- and intra-observer reproducibility for cup
      anteversion were +/-2.5 degrees  and +/-2.3 degrees , respectively. Measurement
      accuracy compared with CT was +/-3.9 degrees . CONCLUSION: EOS imaging system is
      superior to standard radiography in terms of measuring acetabular anteversion and
      inclination.

PMID- 22949125
TI  - Loss of PBRM1 expression is associated with renal cell carcinoma progression.
AB  - Although von Hippel-Lindau (VHL) tumor suppressor gene alterations dominate the
      genetic landscape of clear cell renal cell carcinoma (ccRCC), recent studies have
      identified new ccRCC genes, including SETD2, KDM6A, KDM5C, BAP1 and PBRM1.
      Strikingly, all these genes fall into a category of histone/chromatin regulators.
      Polybromo-1 (PBRM1) is the second most frequently mutated gene after VHL;
      however, the clinical relevance of its loss in ccRCC has not yet been reported.
      Here, we analyzed the expression of PBRM1, the product encoded by PBRM1, in ccRCC
      cell lines and in more than 300 RCC tumor samples. The data were correlated with
      clinicopathological parameters and VHL mutation status. We found that a
      significant number of ccRCC cancer cell lines lack detectable PBRM1 expression.
      Loss of PBRM1 was predominant in the clear cell subtype of RCC (~ 70%) and
      correlated with advanced tumor stage (p < 0.0001), low differentiation grade (p =
      0.0002) and worse patient outcome (p = 0.025), but not with the VHL mutation
      status. Our results indicate a critical role for PBRM1 in the suppression of
      ccRCC progression. Moreover, the results suggest that functional inactivation of
      PBRM1 in the context of pVHL loss-of-function may represent a key event in
      facilitating the development of key aspects of an aggressive tumor behavior.
      Given the role of PBRM1 in chromatin modification, the gene expression pathways
      disrupted by the inactivation of this protein may lead to new treatment
      strategies for ccRCC.

PMID- 22949127
TI  - A child with progressive multiple tracheal diverticulae: a variation of the
      Mounier-Kuhn syndrome.
AB  - Mounier-Kuhn syndrome is a rare disorder characterized by tracheobronchomegaly.
      Most commonly presenting in adults, a broad spectrum of clinical abnormalities
      has been described. We report a young woman followed since 4 years of age for
      respiratory symptoms who was eventually found to have tracheobronchomegaly and
      multiple tracheal diverticulae.

PMID- 22949126
TI  - Integrins regulate centrosome integrity and astrocyte polarization following a
      wound.
AB  - In response to a wound, astrocytes in culture extend microtubule-rich processes
      and polarize, orienting their centrosomes and Golgi apparatus woundside. beta1
      Integrin null astrocytes fail to extend processes toward the wound, and are
      disoriented, and often migrate away orthogonal, to the wound. The centrosome is
      unusually fragmented in beta1 integrin null astrocytes. Expression of a beta1
      integrin cDNA in the null background yields cells with intact centrosomes that
      polarize and extend processes normally. Fragmented centrosomes rapidly assemble
      following integrin ligation and cell attachment. However, several experiments
      indicated that cell adhesion is not necessary. For example, astrocytes in
      suspension expressing a chimeric beta1 subunit that can be activated by an
      antibody assemble centrosomes suggesting that beta1 activation is sufficient to
      cause centrosome assembly in the absence of cell adhesion. siRNA knockdown of
      PCM1, a major centrosomal protein, inhibits cell polarization, consistent with
      the notion that centrosomes are necessary for polarity and that integrins
      regulate polarity via centrosome integrity. Screening inhibitors of molecules
      downstream of integrins indicate that neither FAK nor ILK is involved in
      regulation of centrosome integrity. In contrast, blebbistatin, a specific
      inhibitor of non-muscle myosin II (NMII), mimics the response of beta1 integrin
      null astrocytes by disrupting centrosome integrity and cell polarization.
      Blebbistatin also inhibits integrin-mediated centrosome assembly in astrocytes
      attaching to fibronectin, consistent with the hypothesis that NMII functions
      downstream of integrins in regulating centrosome integrity.

PMID- 22949128
TI  - The use of ascorbate as an oxidation inhibitor in prebiotic amino acid synthesis:
      a cautionary note.
AB  - It is generally thought that the terrestrial atmosphere at the time of the origin
      of life was CO(2)-rich and that organic compounds such as amino acids would not
      have been efficiently formed abiotically under such conditions. It has been
      pointed out, however, that the previously reported low yields of amino acids may
      have been partially due to oxidation by nitrite/nitrate during acid hydrolysis.
      Specifically, the yield of amino acids was found to have increased significantly
      (by a factor of several hundred) after acid hydrolysis with ascorbic acid as an
      oxidation inhibitor. However, it has not been shown that CO(2) was the carbon
      source for the formation of the amino acids detected after acid hydrolysis with
      ascorbic acid. We therefore reinvestigated the prebiotic synthesis of amino acids
      in a CO(2)-rich atmosphere using an isotope labeling experiment. Herein, we
      report that ascorbic acid does not behave as an appropriate oxidation inhibitor,
      because it contributes amino acid contaminants as a consequence of its reactions
      with the nitrogen containing species and formic acid produced during the spark
      discharge experiment. Thus, amino acids are not efficiently formed from a CO(2)
      rich atmosphere under the conditions studied.

PMID- 22949129
TI  - Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter
      pylori gastritis.
AB  - The recognition and removal of apoptotic inflammatory cells by tissue macrophages
      and non-professional phagocytes, in a process called efferocytosis, is required
      for resolution of inflammation and is actively anti-inflammatory. We have
      previously demonstrated phagocytosis of apoptotic neutrophils by tumor cells in
      human gastric carcinoma, but to date, there have been no studies investigating
      this process in chronic active Helicobacter pylori gastritis. Biopsy specimens
      from 28 subjects with or without H. pylori infection and active inflammation were
      examined and graded according to the updated Sydney system. Light microscopy,
      electron microscopy, and Terminal Deoxynucleotidyltransferase-Mediated UTP End
      Labeling staining were used to identify apoptosis. H. pylori infection was
      detected by histology and by molecular assay in 16 out of 28 cases. DNA from
      paraffin-embedded gastric biopsies was amplified using primers specific for cagA,
      for the cag "empty site" as well as for the s and m alleles of vacA. The more
      virulent cagA-positive strains were found in five out of nine patients with
      chronic active gastritis. The vacA s1/m1 and s2/m1 genotypes were more common in
      nine patients with chronic active gastritis, while the vacA s2/m2 genotype was
      more frequent in seven patients with chronic inactive gastritis. Apoptotic
      neutrophils were also detected within the cytoplasmic vacuoles of the foveolar
      cells of nine cases with chronic active gastritis. Transmission electron
      micrographs revealed further apoptotic neutrophils within spacious phagosomes of
      foveolar cells in a similar manner to those described in late-phase efferocytosis
      both in vivo and in vitro. These new observations expand the morphological
      spectrum of gastritis in patients infected with more virulent H. pylori strains,
      compatible with an anti-inflammatory role for the gastric epithelial cells in
      their removal of apoptotic neutrophils during active chronic gastritis.

PMID- 22949130
TI  - Receipt of locoregional therapy among young women with breast cancer.
AB  - Although younger women with breast cancer have the most to gain from receipt of
      optimal care, few data are available regarding their receipt of locoregional
      breast cancer treatments. We identified 317,596 women aged 18-64 who were
      diagnosed with invasive breast cancer at hospitals reporting to the National
      Cancer Database, a large national cancer registry, during 2004-2008. We used
      multivariable logistic regression to assess the association of patient age with
      mastectomy versus breast-conserving surgery (BCS), radiation with BCS, and
      postmastectomy radiation therapy (PMRT) with varying indications, adjusting for
      patient, clinical, and facility characteristics. Overall, 4 % of women were 35
      years old or younger and 7 % were 36-40 years old. Women <=age 40 were
      significantly more likely to have mastectomy than BCS compared with older women
      (57 % for age <=35 and 52 % for ages 36-40 vs. 35 % for ages 61-64, adjusted odds
      ratio [OR] for age <=35 = 2.03; 95 % confidence interval (CI) 1.93-2.14 and OR
      for ages 36-40 = 1.76; 95 % CI 1.69-1.84). Younger women were less likely to
      receive radiation if BCS was performed (69 and 73 vs. 80 %, OR for age <=35 =
      0.69; 95 % CI 0.65-0.74 and OR for ages 36-40 = 0.74; 95 % CI 0.70-0.78). For
      those who underwent mastectomy, overall rates of PMRT were low, although women
      <=age 35 and ages 36-40 (vs. ages 61-64) were more likely to receive PMRT
      regardless of clinical indications. Our study suggests that young women with
      breast cancer may not be receiving optimal locoregional therapy. Efforts are
      needed to confirm these findings, further understand barriers to care, and
      increase the receipt of appropriate adjuvant radiation therapy among young women
      to improve their disease-free and overall survival.

PMID- 22949131
TI  - Dapsone 5% gel: a new option in topical therapy for acne.
AB  - Dapsone 5% gel for the topical treatment for acne vulgaris was recently
      introduced in Canada. It represents the first new anti-acne agent to gain North
      American regulatory approval in the past decade. Dapsone's utility is
      attributable to its anti-inflammatory and antimicrobial properties that improve
      both inflammatory and non-inflammatory acne, with more prominent effects
      occurring in inflammatory lesions. Short- and long-term safety and efficacy have
      been demonstrated. Especially for patients exhibiting sensitivities or
      intolerance to conventional anti-acne agents, topical dapsone is a novel addition
      to the treatment armamentarium.

PMID- 22949132
TI  - Prevention and treatment of pressure ulcers.
AB  - Pressure ulcer prevention and treatment remains a challenge for interprofessional
      teams in all health care sectors. Evidencebased pressure ulcer guidelines can be
      simplified with a bedside enabler utilizing the wound bed preparation paradigm.
      Key steps involve treatment of the cause, addressing patient-centered concerns,
      and administering local wound care (debridement, infection/ inflammation control,
      and moisture balance before considering advanced therapies with the edge effect).
      Optimal outcomes are achievable with a multi-disciplinary approach that supports
      patients and their circle of care, which is central to every evaluation and
      course of treatment decisions.

PMID- 22949134
TI  - Internet-based chat support groups for parents in family-based treatment for
      adolescent eating disorders: a pilot study.
AB  - OBJECTIVE: This study aims to examine the feasibility and acceptability of an
      Internet-based chat support group for parents implementing family-based treatment
      (FBT). METHOD: Participants (N = 13) were parents of adolescents with eating
      disorder who participated in 15 weekly online therapist-guided chat sessions.
      Sessions focused on encouraging and supporting parental efforts to help their
      child overcome an eating disorder. RESULTS: Chat programme satisfaction ratings
      were high (91.7%). Participants reported looking forward to chat sessions and
      would recommend the chat to others. The vast majority reported that the chat
      helped them cope with their child's eating disorder and to implement FBT.
      Participants reported feeling that they could talk openly and honestly in
      sessions and had a sense of belonging to the group. Relatively few technical
      problems were reported, and the chat was rated as accessible, convenient and easy
      to use. DISCUSSION: Findings provide preliminary support for the utility of an
      online parent chat as an adjunct to FBT.

PMID- 22949133
TI  - Mortality in young adults following in utero and childhood exposure to arsenic in
      drinking water.
AB  - BACKGROUND: Beginning in 1958, the city of Antofagasta in northern Chile was
      exposed to high arsenic concentrations (870 ug/L) when it switched water sources.
      The exposure abruptly stopped in 1970 when an arsenic-removal plant commenced
      operations. A unique exposure scenario like this--with an abrupt start, clear
      end, and large population (125,000 in 1970), all with essentially the same
      exposure--is rare in environmental epidemiology. Evidence of increased mortality
      from lung cancer, bronchiectasis, myocardial infarction, and kidney cancer has
      been reported among young adults who were in utero or children during the high
      exposure period. OBJECTIVE: We investigated other causes of mortality in
      Antofagasta among 30- to 49-year-old adults who were in utero or <= 18 years of
      age during the high-exposure period. METHODS: We compared mortality data between
      Antofagasta and the rest of Chile for people 30-49 years of age during 1989-2000.
      We estimated expected deaths from mortality rates in all of Chile, excluding
      Region II where Antofagasta is located, and calculated standardized mortality
      ratios (SMRs). RESULTS: We found evidence of increased mortality from bladder
      cancer [SMR = 18.1; 95% confidence interval (CI): 11.3, 27.4], laryngeal cancer
      (SMR = 8.1; 95% CI: 3.5, 16.0), liver cancer (SMR = 2.5; 95% CI: 1.6, 3.7), and
      chronic renal disease (SMR = 2.0; 95% CI: 1.5, 2.8). CONCLUSIONS: Taking together
      our findings in the present study and previous evidence of increased mortality
      from other causes of death, we conclude that arsenic in Antofagasta drinking
      water has resulted in the greatest increases in mortality in adults < 50 years of
      age ever associated with early-life environmental exposure.

PMID- 22949135
TI  - The impact of social support on outcomes in adult patients with type 2 diabetes:
      a systematic review.
AB  - Diabetes is one of the fastest growing chronic diseases globally and in the
      United States. Although preventable, type 2 diabetes accounts for 90 % of all
      cases of diabetes worldwide and continues to be a source of increased disability,
      lost productivity, mortality, and amplified health-care costs. Proper disease
      management is crucial for achieving better diabetes-related outcomes. Evidence
      suggests that higher levels of social support are associated with improved
      clinical outcomes, reduced psychosocial symptomatology, and the adaptation of
      beneficial lifestyle activities; however, the role of social support in diabetes
      management is not well understood. The purpose of this systematic review is to
      examine the impact of social support on outcomes in adults with type 2 diabetes.

PMID- 22949136
TI  - A culturally adapted family intervention for African American families coping
      with parental cancer: outcomes of a pilot study.
AB  - OBJECTIVES: The primary objective of this 2-year pilot study was to evaluate the
      effectiveness of a culturally adapted family intervention in improving family
      communication among African American parents coping with cancer and their school
      age children. A secondary objective was to determine its impact on other symptoms
      of psychosocial distress (depression and anxiety). The third objective was to
      assess for acceptability and feasibility. METHODS: Using a two-arm pre
      intervention and post-intervention prospective design, 12 African American
      families received five bi-monthly sessions of either a culturally adapted family
      intervention (n=7 families) or psycho-education treatment (n=5 families). Parents
      and their children completed pre-intervention and post-intervention
      questionnaires assessing perceptions of family communication, quality of their
      relationship, and symptoms of depression. School-age children additionally
      completed a questionnaire assessing their levels of anxiety. Consumer
      satisfaction was also evaluated at post-intervention. RESULTS: Parents and school
      age children who completed the culturally adapted family intervention reported
      significantly better communication with each other and were more satisfied
      compared with the psycho-education control group. No changes were noted in
      symptoms of anxiety or depression. The culturally adapted family intervention was
      acceptable based on our findings, families' feedback, and rates of retention.
      Feasibility is uncertain because our oncology clinic approach to recruitment was
      slower than expected. CONCLUSIONS: Providing culturally adapted family
      intervention programs to African American families who are coping with parental
      cancer may result in improved family communication. This pilot study serves as
      the first step in the development of culturally adapted family intervention
      programs to help African American families cope with parental cancer.

PMID- 22949137
TI  - Prevention and control of surgical site infections: review of the Basel Cohort
      Study.
AB  - INTRODUCTION: Surgical site infections (SSI) are the most common hospital
      acquired infections among surgical patients, with significant impact on patient
      morbidity and health care costs. The Basel SSI Cohort Study was performed to
      evaluate risk factors and validate current preventive measures for SSI. The
      objective of the present article was to review the main results of this study and
      its implications for clinical practice and future research. SUMMARY OF METHODS OF
      THE BASEL SSI COHORT STUDY: The prospective observational cohort study included
      6,283 consecutive general surgery procedures closely monitored for evidence of
      SSI up to 1 year after surgery. The dataset was analysed for the influence of
      various potential SSI risk factors, including timing of surgical antimicrobial
      prophylaxis (SAP), glove perforation, anaemia, transfusion and tutorial
      assistance, using multiple logistic regression analyses. In addition, post hoc
      analyses were performed to assess the economic burden of SSI, the efficiency of
      the clinical SSI surveillance system, and the spectrum of SSI-causing pathogens.
      REVIEW OF MAIN RESULTS OF THE BASEL SSI COHORT STUDY: The overall SSI rate was
      4.7% (293/6,283). While SAP was administered in most patients between 44 and 0
      minutes before surgical incision, the lowest risk of SSI was recorded when the
      antibiotics were administered between 74 and 30 minutes before surgery. Glove
      perforation in the absence of SAP increased the risk of SSI (OR 2.0; CI 1.4-2.8;
      p <0.001). No significant association was found for anaemia, transfusion and
      tutorial assistance with the risk of SSI. The mean additional hospital cost in
      the event of SSI was CHF 19,638 (95% CI, 8,492-30,784). The surgical staff
      documented only 49% of in-hospital SSI; the infection control team registered the
      remaining 51%. Staphylococcus aureus was the most common SSI-causing pathogen
      (29% of all SSI with documented microbiology). No case of an antimicrobial
      resistant pathogen was identified in this series. CONCLUSIONS: The Basel SSI
      Cohort Study suggested that SAP should be administered between 74 and 30 minutes
      before surgery. Due to the observational nature of these data, corroboration is
      planned in a randomized controlled trial, which is supported by the Swiss
      National Science Foundation. Routine change of gloves or double gloving is
      recommended in the absence of SAP. Anaemia, transfusion and tutorial assistance
      do not increase the risk of SSI. The substantial economic burden of in-hospital
      SSI has been confirmed. SSI surveillance by the surgical staff detected only half
      of all in-hospital SSI, which prompted the introduction of an electronic SSI
      surveillance system at the University Hospital of Basel and the Cantonal Hospital
      of Aarau. Due to the absence of multiresistant SSI-causing pathogens, the
      continuous use of single-shot single-drug SAP with cefuroxime (plus metronidazole
      in colorectal surgery) has been validated.

PMID- 22949138
TI  - Characteristics of the binding of a bacterial expansin (BsEXLX1) to
      microcrystalline cellulose.
AB  - Plant expansin proteins induce plant cell wall extension and have the ability to
      extend and disrupt cellulose. In addition, these proteins show synergistic
      activity with cellulases during cellulose hydrolysis. BsEXLX1 originating from
      Bacillus subtilis is a structural homolog of a beta-expansin produced by Zea mays
      (ZmEXPB1). The Langmuir isotherm for binding of BsEXLX1 to microcrystalline
      cellulose (i.e., Avicel) revealed that the equilibrium binding constant of
      BsEXLX1 to Avicel was similar to those of other Type A surface-binding
      carbohydrate-binding modules (CBMs) to microcrystalline cellulose, and the
      maximum number of binding sites on Avicel for BsEXLX1 was also comparable to
      those on microcrystalline cellulose for other Type A CBMs. BsEXLX1 did not bind
      to cellooligosaccharides, which is consistent with the typical binding behavior
      of Type A CBMs. The preferential binding pattern of a plant expansin, ZmEXPB1, to
      xylan, compared to cellulose was not exhibited by BsEXLX1. In addition, the
      binding capacities of cellulose and xylan for BsEXLX1 were much lower than those
      for CtCBD3.

PMID- 22949140
TI  - Hydroxyurea treatment of children with hemoglobin SC disease.
AB  - The efficacy of hydroxyurea in hemoglobin SC (HbSC) patients is not well
      documented. We describe the long-term response to hydroxyurea in children with
      clinically severe HbSC. In 15 patients, hydroxyurea resulted in a significant
      increase in mean corpuscular volume (MCV) and fetal hemoglobin (HbF) and a
      significant decrease in episodes of acute chest syndrome and hospitalization for
      pain; there was no effect on hemoglobin level. The most significant side effect
      was thrombocytopenia, which led to discontinuation of treatment in one patient.
      This study suggests that hydroxyurea has efficacy and is safe for long-term
      therapy in patients with HbSC.

PMID- 22949139
TI  - Post-transplant consolidation therapy using thalidomide alone for the patients
      with multiple myeloma: a feasibility study in Japanese population.
AB  - In order to test for improved survival following autologous transplantation
      (ASCT), we conducted a prospective clinical trial of post-ASCT thalidomide
      therapy in Japanese patients with multiple myeloma (MM). Twenty-five newly
      diagnosed patients received double or single ASCT with high-dose melphalan (200
      mg/m(2)). Two months after stem cell infusion, if the patients failed to achieve
      a near-complete response, thalidomide was administered at 200 mg/day until
      disease progression or occurrence of intolerable adverse events. Seventeen
      patients were in partial response or minimal response after ASCT and received
      thalidomide alone. Their median progression-free survival (PFS) from ASCT was
      17.4 months, and the median overall survival (OS) was 42.9 months. Some patients
      with normal karyotype experienced durable disease stabilization for over 5 years.
      Five patients who exhibited high-risk chromosomal changes such as t(4;14) or
      deletion of chromosome 13 or 17 showed very short PFS and OS compared with those
      who did not. Observed grade 3 or 4 toxicities included infection in three
      patients, hematological toxicities in three, and gastrointestinal toxicities in
      two, but there was no grade 3 or higher peripheral neuropathy, probably due to
      appropriate dose modifications. This long-term prospective study is the first to
      demonstrate the feasibility of post-ASCT thalidomide therapy in Japanese patients
      with MM.

PMID- 22949141
TI  - Is microalbuminuria a disease?

PMID- 22949142
TI  - Expanding role of mineralocorticoid receptor antagonists in the treatment of
      heart failure.
AB  - Despite numerous pharmacologic and nonpharmacologic treatment strategies, heart
      failure remains a complex, progressive disorder with significant morbidity and
      mortality. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II
      receptor blockers (ARBs), and beta-blockers have been used as routine treatment
      options for heart failure for the majority of patients with left ventricular
      systolic dysfunction who tolerate these agents. Mineralocorticoid receptor
      antagonists (MRAs) have also demonstrated significant benefits in the treatment
      of heart failure, which include a reduction in sudden cardiac death and
      ventricular remodeling; however, these agents have not been recommended for most
      patients with heart failure. In the most recent American College of Cardiology
      Foundation and American Heart Association guidelines, MRAs are recommended for
      patients with New York Heart Association class III or IV symptoms or previous
      acute myocardial infarction, provided an absence of contraindications or risk
      factors for developing hyperkalemia. Based on more recent evidence, it is likely
      that future recommendations and guidelines will further expand the use of MRAs to
      patients with mild heart failure as well. These agents have the potential to be
      recommended nearly as universally as ACE inhibitors and beta-blockers because of
      the potential to reduce mortality and hospital admissions for heart failure. The
      risk of hyperkalemia should be carefully assessed when using these drugs;
      nonetheless, new strategies being developed may reduce the occurrence of
      hyperkalemia as well.

PMID- 22949143
TI  - Ulipristal and embryotoxicity--an alternative viewpoint.

PMID- 22949144
TI  - Somatic mosaicism of PCDH19 mutation in a family with low-penetrance EFMR.
AB  - The occurrence of epilepsy with mental retardation limited to females (EFMR; MIM
      300088) has been recently associated to mutations in the PCDH19 gene, located on
      chromosome X and encoding for protocadherin 19. EFMR shows a rare X-linked
      inheritance wherein affected females may be segregating a mutation through
      unaffected transmitting males (Fabisiak and Erickson Clin Genet 38(5):353-358,
      1990; Juberg and Hellman J Pediatr 79:726-732, 1971; Ryan et al. Nat Genet
      17(1):92-95, 1997). The description of a pedigree segregating PCDH19 mutations
      from unaffected mothers to patients (Depienne et al. Hum Mutat 32:E1959-1975,
      2011; Dibbens et al. Neurology 76:1514-1519, 2011) complicates disease
      inheritance and genetic counseling. In the present study, we describe a PCDH19
      mutation segregating from an asymptomatic mother to an EFMR patient. In order to
      correlate the healthy phenotype with the genotype of the transmitting mother, we
      quantified in a few tissues the level of the mutant allele by real-time PCR,
      disclosing a somatic mosaicism. This finding has a great impact on genetic
      counseling.

PMID- 22949145
TI  - Denosumab for the treatment of bisphosphonate-refractory hypercalcemia.

PMID- 22949146
TI  - Lung cancer and intensive care: extending our look beyond crude mortality.

PMID- 22949147
TI  - Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves
      survival in a phase III randomized trial in patients with metastatic colorectal
      cancer previously treated with an oxaliplatin-based regimen.
AB  - PURPOSE: Treatment for metastatic colorectal cancer (mCRC) commonly involves a
      fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil,
      leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and
      oxaliplatin, often combined with bevacizumab or an epidermal growth factor
      receptor monoclonal antibody. We studied the effect of adding the novel
      antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United
      States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin,
      including patients who received prior bevacizumab. PATIENTS AND METHODS: Patients
      were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612
      patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI.
      Treatment was administered until disease progression or unacceptable toxicity.
      The primary end point was overall survival. RESULTS: Adding aflibercept to
      FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI
      (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median
      survival times of 13.50 versus 12.06 months, respectively. Aflibercept also
      significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661
      to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months,
      respectively. The effects on overall survival and PFS exhibited a consistent
      trend across prespecified subgroup analyses, including bevacizumab pretreated
      patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus
      FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P
      = .0001). Adverse effects reported with aflibercept combined with FOLFIRI
      included the characteristic anti-vascular endothelial growth factor effects and
      also reflected an increased incidence of some chemotherapy-related toxicities.
      CONCLUSION: Aflibercept in combination with FOLFIRI conferred a statistically
      significant survival benefit over FOLFIRI combined with placebo in patients with
      mCRC previously treated with oxaliplatin.

PMID- 22949148
TI  - Growing importance of MYC/BCL2 immunohistochemistry in diffuse large B-cell
      lymphomas.

PMID- 22949149
TI  - Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin
      lymphoma.
AB  - PURPOSE: Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for
      cardiopulmonary complications and CNS stroke, although neurocognitive function
      has not been previously examined. The aim of this study was to examine
      neurocognitive and brain imaging outcomes in adult survivors of childhood HL.
      PATIENTS AND METHODS: In all, 62 adult survivors (mean age, 42.2 years; standard
      deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were
      identified by stratified random selection from a large cohort treated with either
      high-dose (>= 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic
      radiation combined with anthracycline (n = 24). Patients underwent neurocognitive
      evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary
      function tests, and physical examinations. RESULTS: Compared with national age
      adjusted norms, HL survivors demonstrated lower performance on sustained
      attention (P = .004), short-term memory (P = .001), long-term memory (P = .006),
      working memory (P < .001), naming speed (P < .001), and cognitive fluency (P =
      .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence
      of cerebrovascular injury. Higher thoracic radiation dose was associated with
      impaired cardiac diastolic function (E/E'; ratio of peak mitral flow velocity of
      early rapid filling [E] to early diastolic velocity of the mitral annulus [E']; P
      = .003), impaired pulmonary function (diffusing capacity of lungs for carbon
      monoxide [DL(co)(corr); P = .04), and leukoencephalopathy (P = .02). Survivors
      with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001).
      Working memory impairment was associated with E/E', although impaired sustained
      attention and naming speed were associated with DL(co)(corr). Neurocognitive
      performance was associated with academic and vocational functioning. CONCLUSION:
      These results suggest that adult long-term survivors of childhood HL are at risk
      for neurocognitive impairment, which is associated with radiologic indices
      suggestive of reduced brain integrity and which occurs in the presence of
      symptoms of cardiopulmonary dysfunction.

PMID- 22949150
TI  - Randomized, phase III study of gemcitabine or erlotinib maintenance therapy
      versus observation, with predefined second-line treatment, after cisplatin
      gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.
AB  - PURPOSE: This phase III study investigated whether continuation maintenance with
      gemcitabine or switch maintenance with erlotinib improves clinical outcome
      compared with observation in patients with advanced non-small-cell lung cancer
      (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction
      chemotherapy. PATIENTS AND METHODS: Four hundred sixty-four patients with stage
      IIIB/IV NSCLC without tumor progression after four cycles of cisplatin
      gemcitabine were randomly assigned to observation or to gemcitabine (1,250
      mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study
      arms. On disease progression, patients in all three arms received pemetrexed (500
      mg/m(2) once every 21 days) as predefined second-line therapy. The primary end
      point was progression-free survival (PFS). RESULTS: PFS was significantly
      prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95%
      CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR,
      0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit
      was consistent across all clinical subgroups. Both maintenance strategies
      resulted in a nonsignificant improvement in overall survival (OS); patients who
      received second-line pemetrexed or with a performance status of 0 appeared to
      derive greater benefit. Exploratory analysis showed that magnitude of response to
      induction chemotherapy may affect the OS benefit as a result of gemcitabine
      maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no
      unexpected adverse events. CONCLUSION: Gemcitabine continuation maintenance or
      erlotinib switch maintenance significantly reduces disease progression in
      patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line
      chemotherapy. Response to induction chemotherapy may affect OS only for
      continuation maintenance.

PMID- 22949151
TI  - Long-term survivors of gastric cancer: a California population-based study.
AB  - PURPOSE: In the United States, gastric cancer is rapidly fatal with a 25% 5-year
      survival. Of the few patients who survive, little is known about their
      demographic, clinical, and tumor characteristics. PATIENTS AND METHODS: Data
      regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma
      diagnosed in California between 1988 and 2005 were obtained from the California
      Cancer Registry, a member of the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) program. A Cox proportional hazards model
      was constructed to understand the independent relationships of patient
      demographic, disease, and treatment factors with survival. RESULTS: We identified
      47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%)
      survived at least 3 years. Variables associated with longer survival were
      localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or
      later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage
      (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or
      moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific
      Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85),
      fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile
      (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size
      more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease
      specific survival (DSS) in patients with tumors originating in the
      fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months).
      Intestinal histology had significantly longer median DSS (28.9 months) compared
      with other (11.0 months) or diffuse (10.1 months) histology. CONCLUSION: Patients
      who survive gastric and GEJ cancer more than 3 years after diagnosis have
      demographic and pathologic characteristics distinct from those who do not
      survive.

PMID- 22949152
TI  - Double-hit diffuse large B-cell lymphoma.

PMID- 22949153
TI  - Is intensive care unit admission an indicator of patient-centered care for
      patients with advanced lung cancer in SEER-medicare?

PMID- 22949154
TI  - Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid
      leukemia: results from the BELA trial.
AB  - PURPOSE: Bosutinib is an oral Src/Abl tyrosine kinase inhibitor. The phase III
      Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA)
      trial compared bosutinib with imatinib in newly diagnosed, chronic-phase chronic
      myeloid leukemia (CML). PATIENTS AND METHODS: A total of 502 patients were
      randomly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day.
      RESULTS: The complete cytogenetic response (CCyR) rate at 12 months was not
      different for bosutinib (70%; 95% CI, 64% to 76%) versus imatinib (68%; 95% CI,
      62% to 74%; two-sided P = .601); therefore, the study did not achieve its primary
      end point. The major molecular response (MMR) rate at 12 months was higher with
      bosutinib (41%; 95% CI, 35% to 47%) compared with imatinib (27%; 95% CI, 22% to
      33%; two-sided P < .001). Time to CCyR and MMR was faster with bosutinib compared
      with imatinib (two-sided P < .001 for both). On-treatment transformation to
      accelerated/blast phase occurred in four patients (2%) on bosutinib compared with
      10 patients (4%) on imatinib. A total of three CML-related deaths occurred on the
      bosutinib arm compared with eight on the imatinib arm. The safety profiles of
      bosutinib and imatinib were distinct; GI and liver-related events were more
      frequent with bosutinib, whereas neutropenia, musculoskeletal disorders, and
      edema were more frequent with imatinib. CONCLUSION: This ongoing trial did not
      meet its primary end point of CCyR at 12 months, despite the observed higher MMR
      rate at 12 months, faster times to CCyR and MMR, fewer on-treatment
      transformations to accelerated/blast phase, and fewer CML-related deaths with
      bosutinib compared with imatinib. Each drug had a distinct safety profile.

PMID- 22949155
TI  - Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine
      using colorectal tumor models.
AB  - To enhance the oncolytic activity of herpes simplex viruses (HSVs) control of
      immune-suppression and immune-resistance by cancer cells is important. Myeloid
      derived suppressor cells (MDSCs), which interfere with tumor-suppressive
      environments, are inhibited by gemcitabine (GEM) treatment. We investigated the
      oncolytic activity and systemic antitumor immunity induced by oncolytic HSVs in
      combination with GEM treatment. A mouse model with subcutaneous tumors on both
      sides of the lateral flanks was used. A highly attenuated HSV type 1, strain
      HF10, was inoculated into one side of each tumor three times following
      intraperitoneal injection of GEM. Histopathological changes and IFN-gamma
      secretion of the tumor and leukocytes in the spleen were analyzed. These
      treatments were repeated to enhance oncolytic activity. HF10 inoculation reduced
      tumor growth only on the HF10-treated side. HF10 inoculation following GEM
      treatment resulted in greater reduction of tumor growth on the HF10-treated
      tumor; furthermore, reduction of tumors on the contralateral untreated side was
      also observed. Necrosis of the tumor was observed in areas where HSV-infected
      cells were detected. F4/80(+)  macrophages around the tumor were eliminated, and
      CD4(+)  T and CD8(+)  T cells increased in the spleen. A single injection of GEM
      decreased CD11b(+) /Gr-1(+)  MDSCs while retaining CD4(+)  T cells and CD8(+)  T
      cells. Repetition of this treatment regimen resulted in even greater reduction of
      tumor growth on both sides and complete rejection in some of the mice.
      Intratumoral injection of oncolytic HSVs following GEM injection reduced MDSCs.
      Repeated treatment with oncolytic HSVs following GEM resulted in enhanced
      oncolytic activity.

PMID- 22949156
TI  - Determination of lower limb microvasculature by intrafemoral arterial injection
      using computed tomography-assisted angiography.
AB  - BACKGROUND: Computed tomography-assisted angiography (CTA) for lower limb
      vasculature can identify perforators only as small as 1 mm in diameter. The
      technique does not clearly show the microvascularity in subdermal layers of the
      skin. This study investigated a novel method of CTA using intrafemoral injection
      of contrast medium instead of intravenous injection to display the vascular
      anatomy of small perforators with a diameter less than 1 mm in the lower
      extremities of rabbits. METHODS: Posterior thigh perforator surgery was performed
      for 15 New Zealand rabbits weighing 2.5 to 3.5 kg. Five rabbits underwent
      anatomic dissection to determine the vascular anatomy of the posterior thigh
      perforator and its location relative to adjacent structures. Of the remaining 10
      rabbits, 5 were subjected to CTA scanning after injection of iodine contrast
      through a microcatheter inserted into the femoral artery, and 5 were subjected to
      CTA scanning through venous injection of contrast media. The latter group was
      designated as the control group (10 extremities). Images were viewed using a
      dedicated workstation. Postoperative outcomes and complications were monitored
      for 7 days after the procedure. RESULTS: All the CTA images of intraartery
      administration clearly showed that the posterior thigh perforators originated
      from the popliteal artery. Injection of contrast agent through the femoral artery
      improved resolution of the CTA, enabling visualization of perforator arteries
      with diameters in the range of 0.3 to 0.4 mm. The images of the control group
      indicated the course of the perforator in the muscle of only six legs. The images
      of the remaining four legs did not display the perforator. The CTA-treated
      animals recovered without any complications. The anatomic dissection matched the
      CTA mapping. CONCLUSIONS: Computed tomography-assisted angiography using
      intraarterial injection of contrast media enables visualization of vessels
      smaller than 1 mm in diameter. The described animal model also showed the
      presence of vascular branches in the subdermis. This imaging technique may help
      in the preoperative design of perforator flaps for use in clinical practice.
      LEVEL OF EVIDENCE III: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 22949157
TI  - Efficient measurement of the sign and the magnitude of long-range proton-carbon
      coupling constants from a spin-state-selective HSQMBC-COSY experiment.
AB  - A spin state-selective Heteronuclear Single-Quantum Multiple-Bond Connectivities
      (HSQMBC-COSY) experiment is proposed to measure the sign and the magnitude of
      long-range proton-carbon coupling constants ((n)J(CH); n > 1) either for
      protonated or for non-protonated carbons in small molecules. The simple
      substitution of the selective 180 degrees  (1)H pulse in the original selHSQMBC
      pulse scheme by a hard one allows the simultaneous evolution of both proton
      proton and proton-carbon coupling constants during the refocusing period and
      enables a final COSY transfer between coupled protons. The successful
      implementation of the IPAP principle leads to separate mixed-phase alpha/beta
      cross-peaks from which (n)J(CH) values can be easily measured by analyzing their
      relative frequency displacements in the detected dimension.

PMID- 22949159
TI  - Developing an amperometric hydrogen peroxide sensor for an exhaled breath
      analysis system.
AB  - In this work, we present a chip-integrated amperometric sensor targeted at the
      detection of hydrogen peroxide (H2O2) in the gaseous phase. Electrode chips are
      manufactured in a series of microfabrication steps and characterized
      electrochemically. Using such devices detection of H2O2 in an aqueous phase is
      shown by means of cyclic voltammetry and amperometry. Furthermore, it is
      discussed that variation of conditions such as the composition of the supporting
      electrolyte largely influences the obtained electrochemical signal. Additionally,
      electrochemical pretreatment of platinum working electrodes aiming at surface
      oxidation improves the limit of detection of the sensor and the linearity of the
      calibration curve at low H2O2 concentrations (<10 MUM). Agarose-coated electrode
      chips are used for the measurement of H2O2 in the gaseous phase. Detection of
      H2O2 is shown in a static and in a flow-through setup. We find a limit of
      detection of approximately 42 ppb. Current work focuses on expanding the
      presented device to detection of H2O2 in exhaled breath condensate.

PMID- 22949158
TI  - Jelly Belly trans-synaptic signaling to anaplastic lymphoma kinase regulates
      neurotransmission strength and synapse architecture.
AB  - In Drosophila, the secreted signaling molecule Jelly Belly (Jeb) activates
      anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase, in multiple
      developmental and adult contexts. We have shown previously that Jeb and Alk are
      highly enriched at Drosophila synapses within the CNS neuropil and neuromuscular
      junction (NMJ) and postulated a conserved intercellular signaling function. At
      the embryonic and larval NMJ, Jeb is localized in the motor neuron presynaptic
      terminal whereas Alk is concentrated in the muscle postsynaptic domain
      surrounding boutons, consistent with anterograde trans-synaptic signaling. Here,
      we show that neurotransmission is regulated by Jeb secretion by functional
      inhibition of Jeb-Alk signaling. Jeb is a novel negative regulator of
      neuromuscular transmission. Reduction or inhibition of Alk function results in
      enhanced synaptic transmission. Activation of Alk conversely inhibits synaptic
      transmission. Restoration of wild-type postsynaptic Alk expression in Alk partial
      loss-of-function mutants rescues NMJ transmission phenotypes and confirms that
      postsynaptic Alk regulates NMJ transmission. The effects of impaired Alk
      signaling on neurotransmission are observed in the absence of associated changes
      in NMJ structure. Complete removal of Jeb in motor neurons, however, disrupts
      both presynaptic bouton architecture and postsynaptic differentiation.
      Nonphysiologic activation of Alk signaling also negatively regulates NMJ growth.
      Activation of Jeb-Alk signaling triggers the Ras-MAP kinase cascade in both pre-
      and postsynaptic compartments. These novel roles for Jeb-Alk signaling in the
      modulation of synaptic function and structure have potential implications for
      recently reported Alk functions in human addiction, retention of spatial memory,
      cognitive dysfunction in neurofibromatosis, and pathogenesis of amyotrophic
      lateral sclerosis.

PMID- 22949160
TI  - Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary
      exacerbations: IV. colistimethate sodium.
AB  - Patients with cystic fibrosis (CF) often experience acute pulmonary exacerbations
      (APE) and may be treated with a wide variety of intravenous antibiotics. The aim
      of this review is to provide an evidence-based summary of
      pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies
      utilizing the intravenous (IV) polymixin antibiotic colistimethate sodium (CMS)
      in the treatment of APE and to identify areas where further study is warranted.
      Currently, there is not an international standard on the labeling of CMS
      products. As a result, this has lead to confusion in the interpretation of the
      literature with respect to efficacy, tolerance, and optimal dosing strategy. The
      dosing ranges of IV CMS from the literature are 5.3-12.9 mg/kg/day, maximum 480
      mg per day for 60 kg patient (Colomycin(r) injection-European product) and 8-21.3
      mg/kg/day, maximum 800 mg per day for 60 kg patient (Coly-Mycin M(r) parenteral
      US product).The literature supports a CMS dose of 8 mg/kg/day divided every 8 hr
      (maximum 480 mg/day) for the treatment of APE secondary to Pseudomonas
      aeruginosa. The maximum recommended CMS dose of 480 mg/day is less than is
      recommended by the FDA-approved and CFF dosing guidelines but in agreement with
      UK CF Trust Antibiotic Working Group recommendations. There is debate over the
      frequency of CMS administration (once daily vs. thrice-daily) and its impact on
      resistance and clinical efficacy. Further study is needed to determine the
      tolerability and efficacy of extended-interval dosing of CMS in the treatment of
      APE.

PMID- 22949162
TI  - A randomized controlled study of segmental neuromyotherapy for post-stroke
      hemiplegic shoulder pain.
AB  - OBJECTIVE: To assess the effectiveness of segmental neuromyotherapy combined with
      standard hospital therapy relative to standard therapy alone in patients with
      hemiplegic shoulder pain. DESIGN: Randomized controlled trial. PATIENTS: A total
      of 24 patients with positive Neer's and hand-behind-neck tests received standard
      therapy for shoulder pain. Half of them received additional segmental
      neuromyotherapy. METHODS: Pain severity (visual analogue scale), upper-limb
      function (Fugl-Meyer arm score), and spasticity (Ashworth scale) were evaluated
      at 2 days (T1) and 1 day (T2) pre-treatment, in the middle (T3) and at the end
      (T4) of 4 weeks treatment, and 2 months post-treatment (T5). RESULTS: The
      treatment group showed significant advantage compared with the Control group in
      Fugl-Meyer scores at T4 (p = 0.014) and T5 (p = 0.0078) compared with initial
      values. Significant advantage was also shown in the Neer's test at T4 (p =
      0.014), with borderline significance at T5 (p = 0.072). A larger decrease in pain
      scores reported by the treatment group at T5 (p = 0.068) may have been biased by
      higher rates of spatial neglect in this group. CONCLUSION: Segmental
      neuromyotherapy added to standard therapy provides an advantage in pain relief
      and overall arm function in patients with hemiplegic shoulder pain.

PMID- 22949163
TI  - The role of caregiver contingent responsiveness in promoting compliance in young
      children.
AB  - The purpose of this study was to examine relations between parents' contingent
      responding and the behavior of their young children, in the context of other
      relevant parenting behaviors. Parents were observed interacting with their 3-6
      year-old children during two laboratory tasks. Parent responses to child bids
      were classified into four mutually exclusive categories: contingent responses,
      non-contingent non-negative responses, negative responses, and no response.
      Hierarchical regression analyses were used to examine relations between
      contingent responsiveness and child compliance, after accounting for the quality
      of parent directives and parent negativity. Contingent responsiveness was
      uniquely associated with greater child compliance for mothers during both tasks
      and for fathers during one task. An interaction effect was found, indicating that
      fathers' responsiveness during the second task was associated with greater child
      compliance in older, but not younger, children. Implications for clinical
      practice and future research directions are discussed.

PMID- 22949161
TI  - Status of vitamin D in children with sickle cell disease living in Madrid, Spain.
AB  - Patients with sickle cell disease have vitamin D deficiency and poor bone health
      which makes them prone to have an increased risk of fractures and osteoporosis in
      adulthood. We performed a prospective, cross-sectional study in children
      diagnosed with sickle cell disease living in Madrid, Spain. The purpose of this
      study was to evaluate the status of vitamin D of these children. Patients 0-16
      years old were enrolled between 2008 and 2011. We studied demographics, calcium
      metabolism, and bone health, especially by measuring levels of 25-hydroxyvitamin
      D (25(OH)D), during different seasons of the year, and bone densitometry (beyond
      4 years of age). Seventy-eight children were included in the study. Mean age was
      4.8 +/- 4.3 years, and mean serum 25(OH)D level was 21.50 +/- 13.14 ng/ml, with
      no differences in 25(OH)D levels within different seasons. Fifty-six percent of
      children had levels of 25(OH) vitamin D of <20 ng/ml, whereas 79 and 18 % of them
      had levels of <30 and <11 ng/ml, respectively. Secondary hyperparathyroidism was
      observed in 25 % of children. Densitometry was performed in 33 children, and an
      abnormal z-score was seen in 15.2 % of them with no correlation with levels of
      25(OH)D. CONCLUSIONS: Vitamin D deficiency is highly prevalent in children with
      sickle cell disease, who are residing in Madrid, Spain, and it is detected at a
      young age. We propose that early intervention may increase the possibility of an
      adequate bone density later in life.

PMID- 22949165
TI  - Body dissatisfaction in women across the lifespan: results of the UNC-SELF and
      Gender and Body Image (GABI) studies.
AB  - To explore age differences in current and preferred silhouette and body
      dissatisfaction (current - preferred silhouette discrepancy) in women aged 25-89
      years using figural stimuli [range: 1 (very small) to 9 (very large)]. Data were
      abstracted from two online convenience samples (N = 5868). t-tests with
      permutation-adjusted p-values examined linear associations between mean
      silhouette scores (current, preferred, discrepancy score) and age with/without
      stratification by body mass index (BMI). Modal current silhouette was 5; modal
      preferred silhouette was 4; mean discrepancy score was 1.8. There was no
      significant association between current silhouette and age, but a positive linear
      association between preferred silhouette and age remained after stratification by
      BMI. A significant inverse linear association of silhouette discrepancy score and
      age was found only prior to stratification by BMI. Body dissatisfaction exists in
      women across the adult life span and is influenced by BMI.

PMID- 22949166
TI  - Trends and issues in characterizing early cognitive changes in Parkinson's
      disease.
AB  - In this review, we first discuss trends and issues in measuring cognitive changes
      in PD, including recent efforts to define the diagnostic classification of "PD
      Mild Cognitive Impairment" (PD-MCI). After reviewing some limitations associated
      with this diagnosis, we discuss how measures derived from the neurocognitive
      sciences offer better precision in detecting early cognitive changes in PD. To
      support this idea, we highlight 2 influential lines of current investigation that
      are unveiling novel insights about specific cognitive processes that are
      vulnerable early in PD and of critical importance to clinicians involved in
      treating PD: action control and reward learning and decision making. We conclude
      by highlighting some extant issues and unresolved questions for future
      investigations.

PMID- 22949167
TI  - Enhanced osteoinductivity and osteoconductivity through hydroxyapatite coating of
      silk-based tissue-engineered ligament scaffold.
AB  - Hybrid silk scaffolds combining knitted silk fibers and silk sponge have been
      recently developed for use as ligament-alone grafts. Incorporating an
      osteoinductive phase into the ends of a ligament scaffold may potentially
      generate an integrated "bone-ligament-bone" graft and improve graft
      osteointegration with host bone. To explore the possible application of
      hydroxyapatite (HA) coating in the fabrication of osteoinductive ends of silk
      based scaffold, HA was coated on the hybrid silk scaffold and the effects to the
      bone-related cells were evaluated. HA could be coated in a uniform and controlled
      manner on the silk sponge, using an alternate soaking technology, with the amount
      deposited being dependent on the number of soaking cycles. HA coating also
      progressively reduced the hydrophobicity of silk surface (decreasing water
      contact angle from 87 degrees  to 42-76 degrees , after 1-3 soaking cycles),
      making the HA-coated silk scaffold less favorable for initial cell attachments;
      but the attached cells showed viability and sustained proliferation on the HA
      coated scaffold. As demonstrated by real-time polymerase chain reaction and
      alkaline phosphatase assay, the osteoinductivity of HA-coated silk scaffolds
      resulted in the osteogenic differentiation of bone marrow mesenchymal stem cells,
      and the osteoconductivity of HA-coated silk scaffolds supported osteoblasts
      growth and maintained the properties of mature osteoblasts. These properties of
      HA-coating demonstrated its possible application in fabricating osteoinductive
      ends of the silk-based ligament graft to potentially enhance graft-to-host bone
      integration.

PMID- 22949168
TI  - The cancer-related transcription factor Runx2 modulates cell proliferation in
      human osteosarcoma cell lines.
AB  - Runx2 regulates osteogenic differentiation and bone formation, but also
      suppresses pre-osteoblast proliferation by affecting cell cycle progression in
      the G(1) phase. The growth suppressive potential of Runx2 is normally inactivated
      in part by protein destabilization, which permits cell cycle progression beyond
      the G(1)/S phase transition, and Runx2 is again up-regulated after mitosis. Runx2
      expression also correlates with metastasis and poor chemotherapy response in
      osteosarcoma. Here we show that six human osteosarcoma cell lines (SaOS, MG63,
      U2OS, HOS, G292, and 143B) have different growth rates, which is consistent with
      differences in the lengths of the cell cycle. Runx2 protein levels are cell cycle
      regulated with respect to the G(1)/S phase transition in U2OS, HOS, G292, and
      143B cells. In contrast, Runx2 protein levels are constitutively expressed during
      the cell cycle in SaOS and MG63 cells. Forced expression of Runx2 suppresses
      growth in all cell lines indicating that accumulation of Runx2 in excess of its
      pre-established levels in a given cell type triggers one or more anti
      proliferative pathways in osteosarcoma cells. Thus, regulatory mechanisms
      controlling Runx2 expression in osteosarcoma cells must balance Runx2 protein
      levels to promote its putative oncogenic functions, while avoiding suppression of
      bone tumor growth.

PMID- 22949169
TI  - Generalization of Youden index for multiple-class classification problems applied
      to the assessment of externally validated cognition in Parkinson disease
      screening.
AB  - Routine cognitive screening in Parkinson disease (PD) has become essential for
      management, to track progression and to assess clinical status in therapeutic
      trials. Patients with mild cognitive impairment (PD-MCI) are more likely to
      progress to dementia and therefore need to be distinguished from patients with
      normal cognition and those with dementia. A three-class Youden index has been
      recently proposed to select cut-off points in three-class classification
      problems. In this article, we examine properties of a modification of the three
      class Youden index and propose a generalization to k-class classification
      problems. Geometric and theoretical properties of the modified index J(k) are
      examined. It is shown that J(k) is equivalent to the sum of the k - 1 two-class
      Youden indices for the adjacent classes of the ordered alternative problem given
      that the ordering holds. Methods are applied in the assessment of the Montreal
      Cognitive Assessment test when screening cognition in PD.

PMID- 22949170
TI  - Anion exchange membrane adsorbers for flow-through polishing steps: Part I.
      Clearance of minute virus of mice.
AB  - Membrane adsorbers may be a viable alternative to the packed-bed chromatography
      for clearance of virus, host cell proteins, DNA, and other trace impurities.
      However, incorporation of membrane adsorbers into manufacturing processes has
      been slow due to the significant cost associated with obtaining regulatory
      approval for changes to a manufacturing process. This study has investigated
      clearance of minute virus of mice (MVM), an 18-22 nm parvovirus recognized by the
      FDA as a model viral impurity. Virus clearance was obtained using three
      commercially available anion exchange membrane adsorbers: Sartobind Q(r), Mustang
      Q(r), and ChromaSorb(r). Unlike earlier studies that have focused on a single or
      few operating conditions, the aim here was to determine the level of virus
      clearance under a range of operating conditions that could be encountered in
      industry. The effects of varying pH, NaCl concentration, flow rate, and other
      competing anionic species present in the feed were determined. The removal
      capacity of the Sartobind Q and Mustang Q products, which contain quaternary
      ammonium based ligands, is sensitive to feed conductivity and pH. At
      conductivities above about 20 mS/cm, a significant decrease in capacity is
      observed. The capacity of the ChromaSorb product, which contains primary amine
      based ligands, is much less affected by ionic strength. However the capacity for
      binding MVM is significantly reduced in the presence of phosphate ions. These
      differences may be explained in terms of secondary hydrogen bonding interactions
      that could occur with primary amine based ligands.

PMID- 22949171
TI  - MicroRNA-146a suppresses metastatic activity in brain metastasis.
AB  - Primary lung tumors, breast tumors, and melanoma metastasize mainly in the brain
      where therapy is limited to surgery and radiation. To investigate the molecular
      basis of brain metastases, we isolated brain-trophic metastatic MDA-MB-435-LvBr2
      (LvBr2) cells via left ventricle (LV) injection of MDA-MB-435 cells into
      immunodeficiency (NOD/SCID) mice. Whereas parent MDA-MB-435 cells displayed an
      elongated morphology, LvBr2 cells were round and displayed an aggregated
      distribution. LvBr2 cells expressed lower beta-catenin levels and higher
      heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) levels than parental
      cells. Since microRNAs are known to play an important role in cancer progression
      including metastasis, we screened microRNAs expressed specifically in brain
      metastases. MicroRNA-146a was almost undetectable in LvBr2 cells and highly
      expressed in the parental cells. Overexpression of miR-146a increased beta
      catenin expression and suppressed the migratory and invasive activity of LvBr2
      cells. The miR-146a-elicited decrease in hnRNPC in turn lowered the expression of
      MMP-1, uPA, and uPAR and inhibited the migratory and invasive activity of LvBr2
      cells. Taken together, our findings indicate that miR-146a is virtually absent
      from brain metastases and can suppress their metastatic potential including their
      migratory and invasive activities associated with upregulation of beta-catenin
      and downregulation of hnRNPC.

PMID- 22949172
TI  - A novel accessory molecule Trim59 involved in cytotoxicity of BCG-activated
      macrophages.
AB  - BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell
      contact. In this process membrane proteins play an important role. However, up to
      date, few membrane proteins were revealed. In this study, we selected a surface
      molecule named Trim59, which was specifically expressed on BAM membrane (compared
      with the negative control). We cloned and prokaryoticly expressed the
      extracellular domain of Trim59, purified the recombinant protein and generated
      polyclonal antibodies. Immunohistochemistry showed that Trim59 abundantly
      expressed in spleen, stomach and ovary; intermediately expressed in brain, lung,
      kidney, muscle and intestine; but not in thymus, liver, heart, uterus. Using the
      antibodies to block Trim59 on BAM significantly reduced BAM cytotoxicity against
      MCA207 cells. This demonstrated that Trim59 serves as an indispensable molecule
      in maintaining BAM activity. Overexpression of Trim59 in Raw264.7 cell line
      failed to lyse target MCA207 cells, which potentiated Trim59 per se could not
      enhance macrophage cytotoxicity; on another hand, overexpression of Trim59
      enhance the pinocytosis and Phagocytosis activity of Raw-264.7, which imply
      Trim59 might mediate the cell-molecule interaction. Our results indicate Trim59
      might be an essential accessory molecule in mediating BAM tumoricidal functions;
      and Trim59 is a phagocytosis-correlated molecule.

PMID- 22949173
TI  - An overview of health forecasting.
AB  - Health forecasting is a novel area of forecasting, and a valuable tool for
      predicting future health events or situations such as demands for health services
      and healthcare needs. It facilitates preventive medicine and health care
      intervention strategies, by pre-informing health service providers to take
      appropriate mitigating actions to minimize risks and manage demand. Health
      forecasting requires reliable data, information and appropriate analytical tools
      for the prediction of specific health conditions or situations. There is no
      single approach to health forecasting, and so various methods have often been
      adopted to forecast aggregate or specific health conditions. Meanwhile, there are
      no defined health forecasting horizons (time frames) to match the choices of
      health forecasting methods/approaches that are often applied. The key principles
      of health forecasting have not also been adequately described to guide the
      process. This paper provides a brief introduction and theoretical analysis of
      health forecasting. It describes the key issues that are important for health
      forecasting, including: definitions, principles of health forecasting, and the
      properties of health data, which influence the choices of health forecasting
      methods. Other matters related to the value of health forecasting, and  the
      general challenges associated with developing and using health forecasting
      services are discussed. This overview is a stimulus for further discussions on
      standardizing health forecasting approaches and methods that will facilitate
      health care and health services delivery.

PMID- 22949174
TI  - Microfluidic-assisted synthesis of hemispherical and discoidal chitosan
      microparticles at an oil/water interface.
AB  - This study reports a facile method for the synthesis of hemispherical and
      discoidal chitosan microparticles by a combination of microfluidic technology and
      gelation strategy at an oil/water interface. Utilizing microfluidic
      emulsification in a cross-junction channel, the formation of regular droplets was
      achieved. Following the ionic gelation procedure at the liquid-liquid interface
      of the gelling solution and oil solution in the reservoir pool, either
      hemispherical or discoidal chitosan microparticles were obtained. Special
      emphasis was put on the interface reaction of emulsion gelation parameters such
      as ionic crosslinkers, density modifiers, and surfactants, to tailor the
      morphologies of chitosan particles ranging from 160 to 750 MUm. In addition, the
      proposed microfluidic device is capable of generating relatively uniform
      microparticles with a well-controllable shape and size. Being a simple, low-cost
      and high-throughput process is an added advantage. The synthesized hemispherical
      and discoidal chitosan microparticles can be applied to many applications in the
      pharmaceutical and biomedical arena.

PMID- 22949175
TI  - Commentary on "First hand accounts of events in the laboratory of Prof. Eduard
      Pernkopf" by S.H. Aharinejad and S.W. Carmichael.

PMID- 22949176
TI  - Gout-related health care utilization in US emergency departments, 2006 through
      2008.
AB  - OBJECTIVE: To characterize gout-related emergency department (ED) utilization
      using a nationally representative sample and to examine factors associated with
      the frequency and charges of gout-related ED visits. METHODS: Using the National
      Emergency Department Sample data from 2006-2008, the weighted national frequency
      of gout visits was calculated along with the median ED charge and total national
      ED-related charges. Associations of several patient- and facility-level factors
      were examined with the occurrence of gout visits using multivariable logistic
      regression and with ED-related charges using multivariable linear regression.
      RESULTS: Gout was the primary indication for 168,410 ED visits in 2006, 171,743
      visits in 2007, and 174,823 visits in 2008, accounting for ~0.2% of all visits
      annually and generating ED charges of more than $128 million in 2006, $144
      million in 2007, and $166 million in 2008. Age, male sex, household income
      <$39,000, private insurance, and hospital locations in nonmetropolitan areas and
      the southern US were associated with an increased propensity for ED utilization
      in gout. Higher ED-related charges for gout were associated with female sex, age,
      a higher number of coded diagnoses, and a metropolitan residence. CONCLUSION:
      Gout accounts for a substantial proportion of ED visits, leading to significant
      health care charges. Effective strategies to reduce gout burden in EDs could
      potentially benefit by targeting groups characterized by factors demonstrated to
      be related to a higher ED utilization in gout as identified by our study.

PMID- 22949178
TI  - Successful use of plasmapheresis for granulomatosis with polyangiitis presenting
      as diffuse alveolar hemorrhage.
AB  - Diffuse alveolar hemorrhage (DAH) is uncommon in pediatric patients and is a rare
      presenting sign of granulomatosis with polyangiitis (GPA). We present the case a
      14-year-old girl who presented with respiratory failure secondary to DAH as the
      initial presenting sign of GPA. Her clinical course improved after initiation of
      plasmapheresis therapy and she is now in clinical remission.

PMID- 22949180
TI  - Empathy for pain: the effects of prior experience and sex.
AB  - BACKGROUND: Empathy is considered as both a characteristic trait and a variable
      state. The present experiment examined whether or not prior exposure to pain,
      perceived similarity, sex and attributed pain intensity are associated with state
      empathy for pain. METHODS: The state empathy of students (38 female, 42 male) in
      response to pictures displaying exposure to pressure pain was measured via self
      reports, using a newly developed state empathy scale with the two subscales of
      'emotional response' and 'perspective taking'. Physiological responses were also
      recorded. Half of the participants were exposed to pressure pain prior to the
      experiment. Perceived similarity to the person being exposed to pain and their
      estimated pain intensity were assessed. RESULTS: The results revealed that
      perceived similarity and sex were significantly related to the emotional
      dimension of empathy. This sex difference was partially mediated by the estimated
      intensity of pain. Women rated the intensity of pain more highly and achieved
      higher scores on the emotional response subscale. Exposure to pain predicted
      empathy on the perspective-taking subscale, resulting in higher scores when the
      subject had been exposed to the same pain stimulus. The physiological recordings
      did not correlate with any of the empathy scores. CONCLUSIONS: Greater degrees of
      perceived similarity, being female and higher estimated pain were linked to a
      stronger 'emotional reaction', whereas previous exposure to pain facilitated
      'perspective taking'. Pointing out similarities between people and their past
      experiences, as well as focusing on the imagined discomfort being felt by another
      person, may modulate empathy for pain.

PMID- 22949179
TI  - Decreased neuromuscular function in Crohn's disease patients is not associated
      with low serum vitamin D levels.
AB  - BACKGROUND: Neuromuscular fatigue is a common complaint in Crohn's disease (CD)
      patients. A correlation between serum vitamin D concentrations and neuromuscular
      function has been found in the elderly or non-ambulant populations. AIMS: The aim
      of this study was to determine whether CD patients exhibit impaired neuromuscular
      function and if so, is there a link between vitamin D and neuromuscular function.
      METHODS: Crohn's disease patients (n = 19) with at least one prior small bowel
      resection and matched controls (n = 19) underwent muscle strength and endurance
      testing, vitamin D, and nerve function analysis. RESULTS: Knee extension and
      flexion peak torque (Nm/kg) were greater in the control group than in the CD
      patients (P = 0.04 and 0.014, respectively. A significant difference was found
      between fatigue rates of the rectus femoris (P = 0.015) between CD patients and
      controls, but no difference was found in serum vitamin D levels between groups (P
      = 0.317). Knee extension and flexion torque measurements, with age as a
      covariate, were compared with high and low vitamin D levels. Those subjects with
      high serum vitamin D levels had a significantly greater extension peak torque (P
      = 0.045) and extension average torque (Nm/kg) (P = 0.014) than those with low
      levels. CONCLUSION: Crohn's disease patients with sufficient vitamin D levels
      experienced a 43 % greater extension peak torque. Although vitamin D deficiency
      has been associated with neuromuscular dysfunction, there were no differences in
      serum vitamin D levels between the CD and healthy controls to explain the
      decreased muscle strength.

PMID- 22949181
TI  - How to improve cervical cancer screening in Switzerland?

PMID- 22949182
TI  - Macrophage migration inhibitory factor covalently complexed with phenethyl
      isothiocyanate.
AB  - Macrophage migration inhibitory factor is irreversibly inhibited via covalent
      modification by phenethyl isothiocyanate, a naturally occurring compound with
      anti-inflammatory and anticancer properties. The structure of the modified
      protein obtained from X-ray diffraction data to 1.64 A resolution is presented.
      The inhibitor sits within a deep hydrophobic pocket between subunits of the
      homotrimer and is highly ordered. The secondary structure of macrophage migratory
      inhibitory factor is unchanged by this modification, but there are significant
      rearrangements, including of the side-chain position of Tyr37 and the main chain
      of residues 31-34. These changes may explain the decreased binding of the
      modified protein to the receptor CD74. Together with the pocket, the areas of
      conformational change define specific targets for the design of more selective
      and potent inhibitors as potential therapeutics.

PMID- 22949183
TI  - Structure of a UDP-glucose dehydrogenase from the hyperthermophilic archaeon
      Pyrobaculum islandicum.
AB  - The crystal structure of an extremely thermostable UDP-glucose dehydrogenase (UDP
      GDH) from the hyperthermophilic archaeon Pyrobaculum islandicum was determined at
      a resolution of 2.0 A. The overall fold was comprised of an N-terminal NAD(+)
      dinucleotide binding domain and a C-terminal UDP-sugar binding domain connected
      by a long alpha-helix, and the main-chain coordinates of the enzyme were similar
      to those of previously studied UDP-GDHs, including the enzymes from Burkholderia
      cepacia, Streptococcus pyogenes and Klebsiella pneumoniae. However, the sizes of
      several surface loops in P. islandicum UDP-GDH were much smaller than the
      corresponding loops in B. cepacia UDP-GDH but were comparable to those of the S.
      pyogenes and K. pneumoniae enzymes. Structural comparison revealed that the
      presence of extensive intersubunit hydrophobic interactions, as well as the
      formation of an intersubunit aromatic pair network, is likely to be the main
      factor contributing to the hyperthermostability of P. islandicum UDP-GDH.

PMID- 22949184
TI  - Structure of the starch-debranching enzyme barley limit dextrinase reveals
      homology of the N-terminal domain to CBM21.
AB  - Barley limit dextrinase (HvLD) is a debranching enzyme from glycoside hydrolase
      family 13 subfamily 13 (GH13_13) that hydrolyses alpha-1,6-glucosidic linkages in
      limit dextrins derived from amylopectin. The structure of HvLD was solved and
      refined to 1.9 A resolution. The structure has a glycerol molecule in the active
      site and is virtually identical to the structures of HvLD in complex with the
      competitive inhibitors alpha-cyclodextrin and beta-cyclodextrin solved to 2.5 and
      2.1 A resolution, respectively. However, three loops in the N-terminal domain
      that are shown here to resemble carbohydrate-binding module family 21 were
      traceable and were included in the present HvLD structure but were too flexible
      to be traced and included in the structures of the two HvLD-inhibitor complexes.

PMID- 22949185
TI  - The role of active-site Phe87 in modulating the organic co-solvent tolerance of
      cytochrome P450 BM3 monooxygenase.
AB  - Understanding the effects of organic co-solvents on protein structure and
      function is pivotal to engineering enzymes for biotransformation in non-aqueous
      solvents. The effects of DMSO on the catalytic activity of cytochrome P450 BM3
      have previously been investigated and the importance of Phe87 in its organic co
      solvent tolerance was identified. To probe the DMSO inactivation mechanism and
      the functional role of Phe87 in modulating the organic co-solvent tolerance of
      P450 BM3, the haem domain (Thr1-Leu455) of the F87A variant was cocrystallized in
      the presence of 14%(v/v) and 28%(v/v) DMSO. At both DMSO concentrations the
      protein retained the canonical structure of the P450 haem domain without any sign
      of partial or global unfolding. Interestingly, a DMSO molecule was found in the
      active site of both structures, with its O atom pointing towards the haem iron.
      The orientation of the DMSO molecule indicated a dynamic coordination process
      that was in competition with the active-site water molecule. The ability of the
      DMSO molecule to coordinate the haem iron is plausibly the main reason why P450
      BM3 is inactivated at elevated DMSO concentrations. The data allowed an
      interesting comparison with the wild-type structures reported previously. A DMSO
      molecule was found when the wild-type protein was placed in 28%(v/v) DMSO, in
      which the DMSO molecule coordinated the haem iron directly via its S atom.
      Intriguingly, no DMSO molecule was observed at 14%(v/v) DMSO for the wild-type
      structure. These results suggested that the bulky phenyl side chain of Phe87
      protects the haem from being accessed by the DMSO molecule and explains the
      higher tolerance of the wild-type enzyme towards organic co-solvents compared
      with its F87A variant.

PMID- 22949186
TI  - Structure of anabolic ornithine carbamoyltransferase from Campylobacter jejuni at
      2.7 A resolution.
AB  - Anabolic ornithine transcarbamoylase (aOTC) catalyzes the reaction between
      carbamoyl phosphate (CP) and L-ornithine (ORN) to form L-citrulline and phosphate
      in the urea cycle and L-arginine biosynthesis. The crystal structure of
      unliganded aOTC from Campylobacter jejuni (Cje aOTC) was determined at 2.7 A
      resolution and refined to an R(work) of 20.3% and an R(free) of 24.0%. Cje aOTC
      is a trimer that forms a head-to-head pseudohexamer in the asymmetric unit. Each
      monomer is composed of an N-terminal CP-binding domain and a C-terminal ORN
      binding domain joined by two interdomain helices. The Cje aOTC structure presents
      an open conformation of the enzyme with a relatively flexible orientation of the
      ORN-binding domain respective to the CP-binding domain. The conformation of the
      B2-H3 loop (residues 68-78), which is involved in binding CP in an adjacent
      subunit of the trimer, differs from that seen in homologous proteins with CP
      bound. The loop containing the ORN-binding motif (DxxxSMG, residues 223-230) has
      a conformation that is different from those observed in unliganded OTC structures
      from other species, but is similar to those in structures with bound ORN analogs.
      The major differences in tertiary structure between Cje aOTC and human aOTC are
      described.

PMID- 22949187
TI  - Structural insights into ChpT, an essential dimeric histidine phosphotransferase
      regulating the cell cycle in Caulobacter crescentus.
AB  - Two-component and phosphorelay signal-transduction proteins are crucial for
      bacterial cell-cycle regulation in Caulobacter crescentus. ChpT is an essential
      histidine phosphotransferase that controls the activity of the master cell-cycle
      regulator CtrA by phosphorylation. Here, the 2.2 A resolution crystal structure
      of ChpT is reported. ChpT is a homodimer and adopts the domain architecture of
      the intracellular part of class I histidine kinases. Each subunit consists of two
      distinct domains: an N-terminal helical hairpin domain and a C-terminal
      alpha/beta domain. The two N-terminal domains are adjacent within the dimer,
      forming a four-helix bundle. The ChpT C-terminal domain adopts an atypical
      Bergerat ATP-binding fold.

PMID- 22949188
TI  - Purification, crystallization and preliminary X-ray characterization of the
      Acetivibrio cellulolyticus type I cohesin ScaC in complex with the ScaB dockerin.
AB  - The cellulosome, a highly elaborate extracellular multi-enzyme complex of
      cellulases and hemicellulases, is responsible for the efficient degradation of
      plant cell-wall carbohydrates by anaerobic microorganisms. Cohesin and dockerin
      recognition pairs are integral to the architecture of the cellulosome. Thus, type
      I cohesin:dockerins are important for attaching the modular enzymatic components
      to primary scaffoldins to form the cellulosome. In contrast, type II dockerins
      located in primary scaffoldins bind to anchoring scaffoldins, thus contributing
      to the cell-surface attachment of the entire complex. Since anchoring scaffoldins
      usually contain more than one type II cohesin, they contribute to the assembly of
      polycellulosomes. Acetivibrio cellulolyticus possesses an extremely complex
      cellulosome arrangement which is organized by a primary enzyme-binding scaffoldin
      (ScaA), two anchoring scaffoldins (ScaC and ScaD) and an unusual adaptor
      scaffoldin (ScaB). A ScaB dockerin mutated to inactivate one of the two putative
      cohesin-binding interfaces complexed with the ScaC cohesin from A. cellulolyticus
      has been purified and crystallized and data were collected from tetragonal and
      monoclinic crystal forms to resolutions of 1.5 and 6.0 A, respectively.

PMID- 22949189
TI  - Crystallization and preliminary crystal structure analysis of the ligand-binding
      domain of PqsR (MvfR), the Pseudomonas quinolone signal (PQS) responsive quorum
      sensing transcription factor of Pseudomonas aeruginosa.
AB  - The opportunistic bacterial pathogen Pseudomonas aeruginosa employs three
      transcriptional regulators, LasR, RhlR and PqsR, to control the transcription of
      a large subset of its genes in a cell-density-dependent process known as quorum
      sensing. Here, the recombinant production, crystallization and structure solution
      of the ligand-binding domain of PqsR (MvfR), the LysR-type transcription factor
      that responds to the Pseudomonas quinolone signal (PQS), a quinolone-based quorum
      sensing signal that is unique to P. aeruginosa and possibly a small number of
      other bacteria, is reported. PqsR regulates the expression of many virulence
      genes and may therefore be an interesting drug target. The ligand-binding domain
      (residues 91-319) was produced as a fusion with SUMO, and hexagonal-shaped
      crystals of purified PqsR_91-319 were obtained using the vapour-diffusion method.
      Crystallization in the presence of a PQS precursor allowed data collection to
      3.25 A resolution on a synchrotron beamline, and initial phases have been
      obtained using single-wavelength anomalous diffraction data from seleno-L
      methionine-labelled crystals, revealing the space group to be P6(5)22, with unit
      cell parameters a = b = 116-120, c = 115-117 A.

PMID- 22949190
TI  - Cloning, expression, purification and crystallization of dihydrodipicolinate
      synthase from Agrobacterium tumefaciens.
AB  - Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step of the
      lysine-biosynthesis pathway in bacteria, plants and some fungi. This study
      describes the cloning, expression, purification and crystallization of DHDPS
      (NP_354047.1) from the plant pathogen Agrobacterium tumefaciens (AgT-DHDPS).
      Enzyme-kinetics studies demonstrate that AgT-DHDPS possesses DHDPS activity in
      vitro. Crystals of AgT-DHDPS were grown in the unliganded form and in forms with
      substrate bound and with substrate plus allosteric inhibitor (lysine) bound. X
      ray diffraction data sets were subsequently collected to a maximum resolution of
      1.40 A. Determination of the structure with and without substrate and inhibitor
      will offer insight into the design of novel pesticide agents.

PMID- 22949191
TI  - Cloning, expression, crystallization and preliminary X-ray studies of the
      ferredoxin-NAD(P)+ reductase from the thermophilic cyanobacterium
      Thermosynechococcus elongatus BP-1.
AB  - Ferredoxin-NADP(+) reductase (FNR) is a flavoenzyme that catalyses the reduction
      of NADP(+) in the final step of the photosynthetic electron-transport chain. FNR
      from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 (TeFNR)
      contains an additional 9 kDa domain at its N-terminus relative to chloroplastic
      FNRs and is more thermostable than those from mesophilic cyanobacteria. With the
      aim of understanding the structural basis of the thermostability of TeFNR and
      assigning a structural role to the small additional domain, the gene encoding
      TeFNR with and without an additional domain was engineered for heterologous
      expression and the recombinant proteins were purified and crystallized. Crystals
      of TeFNR without the additional domain belonged to space group P2(1), with unit
      cell parameters a = 55.05, b = 71.66, c = 89.73 A, alpha = 90, beta = 98.21,
      gamma = 90 degrees .

PMID- 22949192
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      crotamine, a myotoxic polypeptide from the Brazilian snake Crotalus durissus
      terrificus.
AB  - Crotamine, a highly basic myotoxic polypeptide (molecular mass 4881 Da) isolated
      from the venom of the Brazilian rattlesnake Crotalus durissus terrificus, causes
      skeletal muscle contraction and spasms, affects the functioning of voltage
      sensitive sodium channels by inducing sodium influx and possesses antitumour
      activity, suggesting potential pharmaceutical applications. Crotamine was
      purified from C. durissus terrificus venom; the crystals diffracted to 1.9 A
      resolution and belonged to the orthorhombic space group I2(1)2(1)2(1) or I222,
      with unit-cell parameters a = 67.75, b = 74.4, c = 81.01 A. The self-rotation
      function indicated that the asymmetric unit contained three molecules. However,
      structure determination by molecular replacement using NMR-determined coordinates
      was unsuccessful and a search for potential derivatives has been initiated.

PMID- 22949193
TI  - Crystallization and preliminary X-ray crystallographic analysis of subunit F (F(1
      94)), an essential coupling subunit of the eukaryotic V(1)V(O)-ATPase from
      Saccharomyces cerevisiae.
AB  - V-ATPases are very complex multi-subunit enzymes which function as proton-pumping
      rotary nanomotors. The rotary and coupling subunit F (F(1-94)) was crystallized
      by the hanging-drop vapour-diffusion method. The native crystals diffracted to a
      resolution of 2.64 A and belonged to space group C222(1), with unit-cell
      parameters a = 47.21, b = 160.26, c = 102.49 A. The selenomethionyl form of the
      F(1-94) I69M mutant diffracted to a resolution of 2.3 A and belonged to space
      group C222(1), with unit-cell parameters a = 47.22, b = 160.83, c = 102.74 A.
      Initial phasing and model building suggested the presence of four molecules in
      the asymmetric unit.

PMID- 22949194
TI  - Crystallographic study of the interaction of the anti-HIV lectin actinohivin with
      the alpha(1-2)mannobiose moiety of gp120 HMTG.
AB  - Actinohivin (AH) is a new potent anti-HIV lectin of microbial origin. In order to
      modify it to produce a more efficient drug, its three-dimensional structure has
      previously been determined with and without the target alpha(1-2)mannobiose
      moiety of the high-mannose-type glycan (HMTG) attached to HIV-1 gp120. However,
      ambiguity remained in the structures owing to packing disorder that was possibly
      associated with peptide fragments attached at the N-terminus. To resolve these
      problems, the duration of cultivation of the AH-producing strain was examined and
      it was found that in a sample obtained from a 20 d culture the heterogeneous
      fragments were completely removed to produce mature AH with high homogeneity. In
      addition, the purification procedures were simplified in order to increase the
      yield of AH and the addition of solvents was also examined in order to increase
      the solubility of AH. AH thus obtained was successfully crystallized with high
      reproducibility in a different form to the previously obtained crystals. The
      crystal diffracted well to beyond 1.90 A resolution and the crystallographic data
      suggested that it contained no packing disorder.

PMID- 22949195
TI  - Preliminary X-ray crystallographic analysis of alpha-carbonic anhydrase from
      Thiomicrospira crunogena XCL-2.
AB  - Thiomicrospira crunogena XCL-2 is a novel sulfur-oxidizing chemolithoautotroph
      that plays a significant role in the sustainability of deep-sea hydrothermal vent
      communities. This recently discovered gammaproteobacterium encodes and expresses
      four carbonic anhydrases (CAs) from three evolutionarily and structurally
      distinct CA families: an alpha-CA, two beta-CAs and a gamma-CA. In order to
      characterize and elucidate the physiological roles of these CAs, X-ray
      crystallographic structural studies have been initiated on the alpha-CA. The
      alpha-CA crystallized in space group C2. The crystals diffracted to a maximum
      resolution of 2.6 A, with unit-cell parameters a = 127.1, b = 102.2, c = 105.0 A,
      beta = 127.3 degrees , and a calculated Matthews coefficient of 2.04 A(3) Da(-1)
      with four identical protein molecules in the crystallographic asymmetric unit. A
      preliminary solution was determined by molecular replacement with the PHENIX
      AutoMR wizard, which had an initial TFZ score of 17.9. Refinement of the
      structure is currently in progress.

PMID- 22949196
TI  - Expression, purification, crystallization and preliminary X-ray analysis of a
      novel N-substituted branched-chain L-amino-acid dioxygenase from Burkholderia
      ambifaria AMMD.
AB  - Ferrous ion- and alpha-ketoglutarate-dependent dioxygenase from Burkholderia
      ambifaria AMMD (SadA) catalyzes the C3-hydroxylation of N-substituted branched
      chain L-amino acids, especially N-succinyl-L-leucine, coupled to the conversion
      of alpha-ketoglutarate to succinate and CO(2). SadA was expressed in Escherichia
      coli, purified and crystallized using the sitting-drop vapour-diffusion method at
      293 K. Crystals of selenomethionine-substituted SadA were obtained using a
      reservoir solution containing PEG 3000 as the precipitant at pH 9.5 and
      diffracted X-rays to 2.4 A resolution. The crystal belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 49.3, b = 70.9, c = 148.2 A. The
      calculated Matthews coefficient (V(M) = 2.1 A(3) Da(-1), 41% solvent content)
      suggested that the crystal contains two molecules per asymmetric unit.

PMID- 22949197
TI  - Crystallization and preliminary X-ray crystallographic analysis of YgjG from
      Escherichia coli.
AB  - Putrescine, one of the polyamines that are found in virtually all living
      organisms, has been implicated as an important biological material. The protein
      YgjG is involved in the putrescine-degradation pathway in Escherichia coli. The
      enzyme is a putrescine:2-oxoglutarate aminotransferase that belongs to the class
      III aminotransferases. In this study, YgjG from E. coli was overexpressed,
      purified and crystallized using the hanging-drop vapour-diffusion method.
      Diffraction data were collected to 2.1 A resolution using synchrotron radiation.
      The crystal belonged to the primitive orthorhombic space group P2(1)2(1)2(1),
      with unit-cell parameters a = 121.1, b = 129.5, c = 131.3 A, and is estimated to
      contain four molecules of YgjG per asymmetric unit.

PMID- 22949198
TI  - Crystallization and preliminary crystallographic analysis of the NheA component
      of the Nhe toxin from Bacillus cereus.
AB  - The nonhaemolytic enterotoxin (Nhe) of Bacillus cereus plays a key role in cases
      of B. cereus food poisoning. The toxin is comprised of three different proteins:
      NheA, NheB and NheC. Here, the expression in Escherichia coli, purification and
      crystallization of the NheA protein are reported. The protein was crystallized by
      the sitting-drop vapour-diffusion method using PEG 3350 as a precipitant. The
      crystals of NheA diffracted to 2.05 A resolution and belonged to space group C2,
      with unit-cell parameters a = 308.7, b = 58.2, c = 172.9 A, beta = 110.6 degrees
      . Calculation of V(M) values suggests that there are approximately eight protein
      molecules per asymmetric unit.

PMID- 22949199
TI  - Crystallization and preliminary X-ray crystallographic studies of Rab6A'(Q72L): a
      GTP-locked form.
AB  - Rab6A, a member of the Ras superfamily of small G proteins, is involved in the
      regulation of vesicle trafficking, which is critical for endocytosis, cell
      differentiation and cell growth. Rab6A can exist in two isoforms termed Rab6A and
      Rab6A'. The substitution of Gln72 by Leu (Q72L) in the Rab6A family blocks GTP
      hydrolysis activity, and this mutation usually causes the Rab6A protein to be in
      a constitutively active form. In this study, in order to understand the
      functional uniqueness of Rab6A' and the molecular mechanism of the control of
      activity by GTP and GDP from the crystal structure, a Rab6A'(Q72L) mutant form
      was overexpressed in Escherichia coli with an engineered N-terminal His tag.
      Rab6A'(Q72L) was then purified to homogeneity and crystallized at 293 K. X-ray
      diffraction data were collected to a resolution of 1.9 A from a crystal belonging
      to space group P22(1)2(1) with unit-cell parameters a = 36.84, b = 96.78, c =
      109.99 A. The asymmetric unit was estimated to contain two molecules.

PMID- 22949200
TI  - Crystallographic characterization of mouse AIM2 HIN-200 domain bound to a 15 bp
      and an 18 bp double-stranded DNA.
AB  - AIM2 (absent in melanoma 2) is an innate immune receptor for cytosolic double
      stranded DNA (dsDNA). The engagement of dsDNA by AIM2 activates the AIM2
      inflammasome, resulting in the cleavage of pro-interleukin-1beta by caspase-1.
      The DNA-binding HIN-200 domain of mouse AIM2 bound to a 15 bp dsDNA and to an 18
      bp dsDNA was purified and crystallized. The AIM2 HIN-200 domain in complex with
      the 15 bp DNA crystallized in the cubic space group I23 or I2(1)3, with unit-cell
      parameter a = 235.60 A. The complex of the AIM2 HIN-200 domain and the 18 bp DNA
      crystallized in a similar unit cell. Diffraction data for the two complexes were
      collected to about 4.0 A resolution. Mutagenesis and DNA-binding studies suggest
      that mouse AIM2 uses a similar surface to human AIM2 to recognize DNA.

PMID- 22949201
TI  - Purification, crystallization and preliminary X-ray analysis of SGR6054, a
      Streptomyces homologue of the mycobacterial integration host factor mIHF.
AB  - The mycobacterial integration host factor (mIHF) is a small nonspecific DNA
      binding protein that is essential for the growth of Mycobacterium smegmatis. mIHF
      homologues are widely distributed among Actinobacteria, and a Streptomyces
      homologue of mIHF is involved in control of sporulation and antibiotic production
      in S. coelicolor A3(2). Despite their important biological functions, a structure
      of mIHF or its homologues has not been elucidated to date. Here, the S. griseus
      mIHF homologue (SGR6054) was expressed and purified from Escherichia coli and
      crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour
      diffusion method. The plate-shaped crystal belonged to space group C2, with unit
      cell parameters a = 88.53, b = 69.35, c = 77.71 A, beta = 96.63 degrees , and
      diffracted X-rays to 2.22 A resolution.

PMID- 22949202
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of succinyl-diaminopimelate desuccinylase (Rv1202, DapE)
      from Mycobacterium tuberculosis.
AB  - Succinyl-diaminopimelate desuccinylase from Mycobacterium tuberculosis (DapE,
      Rv1202) has been cloned, heterologously expressed in Escherichia coli and
      purified using standard chromatographic techniques. Diffraction-quality crystals
      were obtained at acidic pH from ammonium sulfate and PEG and diffraction data
      were collected from two crystals to resolutions of 2.40 and 2.58 A, respectively.
      The crystals belonged to the monoclinic space group P2(1), with unit-cell
      parameters a = 79.7, b = 76.0, c = 82.9 A, beta = 119 degrees . The most probable
      content of the asymmetric unit was two molecules of DapE, which would correspond
      to a solvent content of 56%. Both examined crystals turned out to be pseudo
      merohedrally twinned, with twin operator -h, -k, h + l and twin fractions of
      approximately 0.46 and 0.16, respectively.

PMID- 22949203
TI  - Crystallization and preliminary X-ray analysis of Chandipura virus glycoprotein
      G.
AB  - Fusion in members of the Rhabdoviridae virus family is mediated by the G
      glycoprotein. At low pH, the G glycoprotein catalyzes fusion between viral and
      endosomal membranes by undergoing a major conformational change from a pre-fusion
      trimer to a post-fusion trimer. The structure of the G glycoprotein from
      vesicular stomatitis virus (VSV G), the prototype of Vesiculovirus, has recently
      been solved in its trimeric pre-fusion and post-fusion conformations; however,
      little is known about the structural details of the transition. In this work, a
      soluble form of the ectodomain of Chandipura virus G glycoprotein (CHAV G(th))
      was purified using limited proteolysis of purified virus; this soluble ectodomain
      was also crystallized. This protein shares 41% amino-acid identity with VSV G and
      thus its structure could provide further clues about the structural transition of
      rhabdoviral glycoproteins induced by low pH. Crystals of CHAV G(th) obtained at
      pH 7.5 diffracted X-rays to 3.1 A resolution. These crystals belonged to the
      orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 150.3, b =
      228.2, c = 78.8 A. Preliminary analysis of the data based on the space group and
      the self-rotation function indicated that there was no trimeric association of
      the protomers. This unusual oligomeric status could result from the presence of
      fusion intermediates in the crystal.

PMID- 22949204
TI  - Crystallization and preliminary X-ray crystallographic analysis of the putative
      NADP(H)-dependent oxidoreductase YncB from Vibrio vulnificus.
AB  - The yncB gene product from Vibrio vulnificus, which belongs to the medium-chain
      dehydrogenase/reductase (MDR) superfamily, was crystallized using the microbatch
      crystallization method at 295 K. Diffraction data sets were collected using
      synchrotron radiation. Crystals of selenomethionine-substituted YncB protein
      belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 90.52, b =
      91.56, c = 104.79 A. Assuming the presence of two molecules in the asymmetric
      unit, the solvent content was estimated to be about 57%. Crystals of the YncB
      NADP(H) complex belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell
      parameters a = b = 90.14, c = 105.61 A. Assuming the presence of one molecule in
      the asymmetric unit, the solvent content was estimated to be about 56.42%.

PMID- 22949205
TI  - Purification, crystallization and preliminary X-ray analysis of uracil-DNA
      glycosylase from Sulfolobus tokodaii strain 7.
AB  - Uracil-DNA glycosylase (UDG) specifically removes uracil from DNA by catalyzing
      hydrolysis of the N-glycosidic bond, thereby initiating the base-excision repair
      pathway. Although a number of UDG structures have been determined, the structure
      of archaeal UDG remains unknown. In this study, a deletion mutant of UDG isolated
      from Sulfolobus tokodaii strain 7 (stoUDGDelta) and stoUDGDelta complexed with
      uracil were crystallized and analyzed by X-ray crystallography. The crystals were
      found to belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell
      parameters a = 52.2, b = 52.3, c = 74.7 A and a = 52.1, b = 52.2, c = 74.1 A for
      apo stoUDGDelta and stoUDGDelta complexed with uracil, respectively.

PMID- 22949206
TI  - Crystallization and preliminary crystallographic studies of FoxE from Rhodobacter
      ferrooxidans SW2, an Fe(II) oxidoreductase involved in photoferrotrophy.
AB  - FoxE is a protein encoded by the foxEYZ operon of Rhodobacter ferrooxidans SW2
      that is involved in Fe(II)-based anoxygenic photosynthesis ('photoferrotrophy').
      It is thought to reside in the periplasm, where it stimulates light-dependent
      Fe(II) oxidation. It contains 259 residues, including two haem c-binding motifs.
      As no three-dimensional model is available and there is no structure with a
      similar sequence, crystals of FoxE were produced. They diffracted to 2.44 A
      resolution using synchrotron radiation at the Fe edge. The phase problem was
      solved by SAD using SHELXC/D/E and the experimental maps confirmed the presence
      of two haems per molecule.

PMID- 22949207
TI  - Crystallization and preliminary X-ray characterization of the Vitis vinifera
      fucokinase:GDP-fucose pyrophosphorylase.
AB  - The Vitis vinifera dual-activity fucose and nucleotide-sugar metabolizing enzyme
      L-fucokinase:GDP-fucose pyrophosphorylase (FKP) has been purified to homogeneity
      and the 118.8 kDa monomeric protein has been crystallized by vapor diffusion in
      Zeppezauer tubes at 277 K. Crystals of the apoenzyme diffracted to 2.6 A
      resolution and belonged to the tetragonal space group P4(1)2(1)2. There is a
      single FKP monomer in the asymmetric unit, giving a Matthews coefficient of 3.22
      A(3) Da(-1) and a solvent content of 61.8%. A complete native data set has been
      collected as a first step in determining the three-dimensional structure of this
      enzyme.

PMID- 22949208
TI  - Production and crystallization of alpha-phosphoglucomutase from Lactococcus
      lactis.
AB  - alpha-Phosphoglucomutase (alpha-PGM) is an enzyme that is essential for the
      growth of Lactococcus lactis. The enzyme links bacterial anabolism with sugar
      utilization through glycolysis by catalyzing the reversible interconversion of
      glucose 6-phosphate and alpha-glucose 1-phosphate. The gene encoding alpha-PGM
      was cloned and overexpressed in L. lactis. The purified protein was functionally
      active and was crystallized with ammonium sulfate as a precipitant using vapour
      diffusion and seeding techniques. Optimized crystals diffracted to 1.5 A
      resolution at a synchrotron source.

PMID- 22949209
TI  - Crystallization and preliminary X-ray characterization of a type III cohesin
      dockerin complex from the cellulosome system of Ruminococcus flavefaciens.
AB  - In Ruminococcus flavefaciens, a predominant fibre-degrading bacterium found in
      ruminants, cellulosomal proteins are anchored to the bacterial cell wall through
      a relatively small ScaE scaffoldin which includes a single type III cohesin. The
      cotton-binding protein CttA consists of two cellulose-binding modules and a C
      terminal modular pair (XDoc) comprising an X-module and a contiguous dockerin,
      which exhibits high affinity towards the ScaE cohesin. Seleno-L-methionine
      labelled derivatives of the ScaE cohesin module and the XDoc from CttA have been
      expressed, copurified and cocrystallized. The crystals belonged to the tetragonal
      space group P4(3)2(1)2, with unit-cell parameters a = b = 78.7, c = 203.4 A, and
      the unit cell contains a single cohesin-XDoc complex in the asymmetric unit. The
      diffraction data were phased to 2.0 A resolution using the anomalous signal of
      the Se atoms.

PMID- 22949210
TI  - Purification and crystallization of mono-ubiquitylated ubiquitin receptor Rpn10.
AB  - Protein ubiquitylation controls nearly all cellular pathways in eukaryotes. A
      repertoire of proteins named ubiquitin (Ub) receptors harbouring ubiquitin
      binding domains (UBDs) recognize ubiquitylated proteins. These Ub receptors
      decode the Ub signal by tethering a UBD or UBDs to a functional domain or
      domains, thus linking the ubiquitylated target to a specific function. The rapid
      dynamics of ubiquitylation/deubiquitylation has impeded the characterization of
      ubiquitylated proteins. To bypass this obstacle, a recently developed synthetic
      system that reconstructs the entire eukaryotic ubiquitylation cascade in
      Escherichia coli was used to purify the mono-ubiquitylated form of the regulatory
      proteasomal non-ATPase subunit (Ub-Rpn10) from Saccharomyces cerevisiae. Here,
      the first crystallization and data collection of Ub-Rpn10 is reported. Purified
      Ub-Rpn10 was crystallized in 12%(w/v) PEG 20,000, 0.1 M MES pH 6.5 and yielded
      thin rhombus-shaped crystals. X-ray analysis revealed that these crystals
      belonged to the monoclinic system C2, with unit-cell parameters a = 107.3, b =
      49.7, c = 81.3 A, alpha = gamma = 90.0, beta = 130.5 degrees . A full synchrotron
      data set has been collected, merged and scaled with a diffraction limit of 3.14
      A.

PMID- 22949211
TI  - Crystallization and preliminary diffraction studies of SFC-1, a carbapenemase
      conferring antibiotic resistance.
AB  - SFC-1, a class A carbapenemase that confers antibiotic resistance, hydrolyzes the
      beta-lactam rings of beta-lactam antibiotics (carbapenems, cephalosporins,
      penicillins and aztreonam). SFC-1 presents an enormous challenge to infection
      control, particularly in the eradication of Gram-negative pathogens. As SFC-1
      exhibits a remarkably broad substrate range, including beta-lactams of all
      classes, the enzyme is a potential target for the development of antimicrobial
      agents against pathogens producing carbapenemases. In this study, SFC-1 was
      cloned, overexpressed, purified and crystallized. The SFC-1 crystal diffracted to
      1.6 A resolution and belonged to the orthorhombic space group P2(1)2(1)2(1), with
      unit-cell parameters a = 65.8, b = 68.3, c = 88.8 A. Two molecules are present in
      the asymmetric unit, with a corresponding V(M) of 1.99 A(3) Da(-1) and a solvent
      content of 38.1%.

PMID- 22949212
TI  - Crystallization and preliminary X-ray crystallographic analysis of Aquifex
      aeolicus SelA, a bacterial selenocysteine synthase.
AB  - Selenocysteine (Sec), the 21st amino acid, is synthesized on its specific tRNA
      (tRNA(Sec)) via a multi-step process. In bacteria, tRNA(Sec) is ligated first
      with serine by seryl-tRNA synthetase, which is followed by Ser-to-Sec conversion
      by Sec synthase (SelA). To elucidate its structure and catalytic mechanism,
      Aquifex aeolicus SelA was crystallized. Although wild-type SelA crystals
      diffracted X-rays poorly (to up to 8 A resolution), the resolution was improved
      by introducing a quadruple point mutation targeting the loop regions and by
      methylating the lysine residues, which yielded 3.9 A resolution diffraction data
      from a full-length SelA crystal. Truncation of the N-terminal region (DeltaN)
      also improved the resolution. A 3.3 A resolution data set for phase determination
      was obtained from a crystal of selenomethionine-substituted Lys-methylated SelA
      DeltaN.

PMID- 22949214
TI  - Introduction: a special issue on tumor microenvironment research in china and
      Asia.

PMID- 22949213
TI  - Soaking of DNA into crystals of archaeal RNA polymerase achieved by desalting in
      droplets.
AB  - Transcription is a fundamental process across the three domains of life and is
      carried out by multi-subunit enzymatic DNA-directed RNA polymerases (RNAPs). The
      interaction of RNAP with nucleic acids is tightly controlled for precise and
      processive RNA synthesis. Whilst a wealth of structural information has been
      gathered on the eukaryotic Pol II in complex with DNA/RNA, no information exists
      on its ancestral counterpart archaeal RNAP. Thus, in order to extend knowledge of
      the archaeal transcriptional apparatus, crystallization of Sulfolobus shibatae
      RNAP (molecular mass of ~400 kDa) with DNA fragments was pursued. To achieve this
      goal, crystal growth was first optimized using a nanoseeding technique. An ad hoc
      soaking protocol was then put into place, which consisted of gently exchanging
      the high-salt buffer used for apo-RNAP crystal growth into a low-salt buffer
      necessary for DNA binding to RNAP. Of the various crystals screened, one
      diffracted to 4.3 A resolution and structural analysis showed the presence of
      bound DNA [Wojtas et al. (2012). Nucleic Acids Res. 40, doi:10.1093/nar/gks692].

PMID- 22949215
TI  - Effects of transmyocardial jet revascularization with chitosan hydrogel on
      channel patency and angiogenesis in canine infarcted hearts.
AB  - The purpose of this study was to investigate whether transmyocardial jet
      revascularization (TMJR) with chitosan scaffolds retains channel patency and
      enhances angiogenesis after acute myocardial infarction (AMI) in a canine model.
      A total of 32 canines were randomly divided into four groups: myocardial
      infarction (MI), normal saline (NS), chitosan hydrogel (CH), and chitosan plus
      growth factor (CH + GF) groups. TMJR was performed surgically using a needle-free
      injector from the epicardium of canines in the NS, CH, and CH + GF groups;
      channels were filled with NS, CH, and CH + GF, respectively. After 6 weeks, the
      patency of the channels and angiogenesis around the channels were assessed by
      hematoxylin-eosin staining, immunohistochemistry, and Masson's trichrome
      staining. Results suggest that the channels in the CH and CH + GF groups may
      retain patency with luminal endothelization. Moreover, the vessel densities of
      the NS, CH, and CH + GF groups were significantly higher than that of the MI
      group, and that of the CH + GF group was the highest (p < 0.05). This study
      suggests that TMJR with chitosan scaffolds may help retain transmyocardial
      channel patency and enhance angiogenesis after AMI in canines.

PMID- 22949216
TI  - Peroxidase immobilized on phospholipid bilayers supported on Au (111) by DTT self
      assembled monolayers: application to dopamine determination.
AB  - In this work, horseradish peroxidase (HRP) was immobilized on
      dimyristoylphosphatidylcholine (DMPC) bilayers supported on Au (111) by
      dithiotreitol (DTT) self-assembled monolayers and used as a nanostructured
      electrochemical biosensor to dopamine determination. The morphology of the
      phospholipid bilayers and the immobilization of HRP to these layers were
      characterized by atomic force microscopy (AFM). Square-wave voltammetry (SWV)
      experiments were done to investigate the performance of the HRP-modified
      electrode. The AFM images indicate that the enzyme is adsorbed at the external
      layer of the lipid bilayer and, although the electrical charges on the surface
      were not measured, the enzyme and phospholipids surface interaction occurs
      probably by electrostatic forces due to the pH used in the experiments.
      Interestingly, the present system can be used as one-shot sensor for the rapid
      detection of dopamine. The analytical performance of this system was linear for
      dopamine concentrations from 3.3 * 10-5 to 1.3 * 10-3  mol L-1 (r = 0.9997) with
      a detection limit of 2.0 * 10-6  mol L-1. Our results indicate that the use of
      HRP-DMPC bilayer system may be useful not only in developing new nanostructured
      materials for technological purposes, but could be very useful in fundamental
      studies to investigate the interactions between different micro-and
      macromolecules, even with soluble proteins, and lipid membranes.

PMID- 22949217
TI  - Mixture-of-exponentials models to explain heterogeneity in studies of the
      duration of Chlamydia trachomatis infection.
AB  - Published studies of the duration of asymptomatic Chlamydia trachomatis infection
      in women have produced diverse estimates, and most reviewers have not attempted
      an evidence synthesis. We review the designs of duration studies, distinguishing
      between the incident cases presenting soon after infection in clinic-based
      studies and prevalent cases ascertained in population screening studies. We
      combine evidence from all studies under fixed-effect (single clearance rate),
      random-effect (study-specific clearance rate), and mixture-of-exponentials
      models, in which there are either two or three classes of infection that clear at
      different rates. We can identify classes as 'passive' infection and fast-clearing
      and slow-clearing infections. We estimate models by Bayesian MCMC and compared
      them using posterior mean residual deviance and the deviance information
      criterion. The single fixed-effect clearance rate model fitted very poorly. The
      random-effect model was adequate but inferior to the two-class and three-class
      mixture of exponentials. According to the two-class model, the proportion in the
      first class was 23% (95% CI: 16-31%), and the mean duration of C. trachomatis
      infection is 1.36 years (95% CI: 1.13-1.63 years). With the three-rate model,
      duration was similar, but identification of the proportions in each class (19%,
      31%, and 49%) was poor. Although the random-effect model was descriptively
      adequate, the extreme degree of between-study variation in the clearance rate it
      predicted lacked biological plausibility. Differences in study recruitment and
      sampling mechanisms, acting through a mixture-of-exponentials model, better
      explains the apparent heterogeneity in duration.

PMID- 22949218
TI  - Rare case of the trunk of the inferior phrenic arteries originating from a common
      stem with a superior additional left renal artery from the abdominal aorta.
AB  - We describe in this article a rare case of a 39-year-old male with an inferior
      phrenic arteries trunk (IPAaT) originating from a common stem with a superior
      additional left renal artery (SAdLRA) from the abdominal aorta as revealed by
      routine multidetector computed tomography angiography. The IPAaT with an
      endoluminal diameter at the origin of 2.8 mm had an upward path with a total
      length of 18.4 mm, forking to the right inferior phrenic artery and left inferior
      phrenic artery. These two arteries had an endoluminal diameter at the origin of
      1.7 mm and 2.0 mm, respectively. The presence of the common stem of the IPAaT
      with a SAdLRA and the length of the IPAaT complicate selective chemoembolization
      of the liver parenchyma.

PMID- 22949219
TI  - Carcinogenicity and hormone studies with the tissue-selective estrogen receptor
      modulator bazadoxifene.
AB  - Bazedoxifene Acetate (BZA) is a selective estrogen receptor modulator (SERM) that
      is approved for the prevention and/or treatment of osteoporosis in postmenopausal
      women. To assess for carcinogenic potential, BZA was administered ad libitum in
      the diet to rats for 2 years. BZA caused an increase in benign ovarian tumors in
      female rats and decreased incidences of mammary tumors (females) and pituitary
      tumors (males and females). In addition, BZA provided a significant survival
      benefit at all dosages tested, which correlated with a significant reduction in
      pituitary and mammary gland tumors and decreased body weight gain (both genders).
      Additional studies were subsequently conducted in rats and monkeys to further
      explore the mechanisms likely responsible for the observed effects. Results from
      studies in hypophysectomized and chemically castrated female rats indicated that
      BZA did not directly stimulate formation of ovarian cysts, but an intact
      pituitary was required for cyst formation. Further, BZA increased estradiol
      concentrations in rats and monkeys. In monkeys, BZA increased concentrations of
      luteinizing hormone (LH) after onset of treatment and prohibited the preovulatory
      surge of LH until after cessation of treatment. These hormonal changes suggest
      that BZA inhibited both the positive and negative feedback effects of estrogen on
      gonadotropins and the resulting increase in LH caused formation and persistence
      of ovarian cysts, which eventually transformed into benign ovarian granulosa cell
      tumors in the rat carcinogenicity study. These results also suggest that the
      reductions in pituitary and mammary gland tumors were attributed to BZA-related
      antagonism of endogenous estrogens at the estrogen receptors.

PMID- 22949220
TI  - Electrophoretically mediated microanalysis for characterization of the
      enantioselective CYP3A4 catalyzed N-demethylation of ketamine.
AB  - Execution of an enzymatic reaction performed in a capillary with subsequent
      electrophoretic analysis of the formed products is referred to as
      electrophoretically mediated microanalysis (EMMA). An EMMA method was developed
      to investigate the stereoselectivity of the CYP3A4-mediated N-demethylation of
      ketamine. Ketamine was incubated in a 50 MUm id bare fused-silica capillary
      together with human CYP3A4 Supersomes using a 100 mM phosphate buffer (pH 7.4) at
      37 degrees C. A plug containing racemic ketamine and the NADPH regenerating
      system including all required cofactors for the enzymatic reaction was injected,
      followed by a plug of the metabolizing enzyme CYP3A4 (500 nM). These two plugs
      were bracketed by plugs of incubation buffer to ensure proper conditions for the
      enzymatic reaction. The rest of the capillary was filled with a pH 2.5 running
      buffer comprising 50 mM Tris, phosphoric acid, and 2% w/v of highly sulfated
      gamma-cyclodextrin. Mixing of reaction plugs was enhanced via application of -10
      kV for 10 s. After an incubation of 8 min at 37 degrees C without power
      application (zero-potential amplification), the capillary was cooled to 25
      degrees C within 3 min followed by application of -10 kV for the separation and
      detection of the formed enantiomers of norketamine. Norketamine formation rates
      were fitted to the Michaelis-Menten model and the elucidated values for V(max) 
      and K(m)  were found to be comparable to those obtained from the off-line assay
      of a previous study.

PMID- 22949222
TI  - A closer look at temporal summation of second pain in healthy persons.

PMID- 22949223
TI  - Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1
      vaccination in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the influence of abatacept (ABA) and associated
      contributing factors on pandemic 2009 influenza A/H1N1 vaccine immunogenicity in
      rheumatoid arthritis (RA) patients. METHODS: The response to a nonadjuvanted
      monovalent pandemic 2009 influenza A/H1N1 killed virus vaccine was analyzed in 11
      RA patients using ABA (RA-ABA), most with concomitant nonbiologic disease
      modifying antirheumatic drugs (DMARDS), and compared to 33 age-matched RA
      patients on methotrexate (MTX) and 55 healthy controls, all without previous
      seroprotection. Clinical and laboratory evaluations were performed before and 21
      days after vaccination. Anti-influenza antibody titers were measured by
      hemagglutination inhibition assay. Seroprotection (antibody titers >=1:40) and
      the factor increase (FI) in the geometric mean titers (GMTs) were calculated.
      Prevaccination lymphocyte counts and gammaglobulin levels were determined.
      RESULTS: Sex distribution, disease duration, and the Disease Activity Score in 28
      joints were similar in the RA groups (P > 0.05). After vaccination,
      seroprotection was significantly reduced in RA-ABA patients compared to RA-MTX
      patients (9% versus 58%; P = 0.006) and controls (69%; P <= 0.001). FI-GMT was
      severely reduced in RA-ABA patients compared to RA-MTX patients (1.8 [1.4-2.3]
      versus 8.7 [5.2-17.4]; P < 0.001) and controls (11.5 [8.0-16.7]; P <= 0.001).
      Lymphocyte counts were comparable in RA groups (P > 0.05), but RA-ABA patients
      had slightly lower gammaglobulin levels than RA-MTX patients (0.9 gm/dl [0.6-1.8]
      versus 1.2 gm/dl [0.8-1.7]; P = 0.03), although almost all were within the normal
      range values. CONCLUSION: The current study established that ABA, in association
      with traditional DMARDs, significantly reduces the humoral response to pandemic
      2009 influenza A/H1N1 vaccine in RA patients. The results suggest an influence of
      costimulatory modulation in humoral response to this vaccine.

PMID- 22949224
TI  - Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary
      exacerbations: III. fluoroquinolones.
AB  - This review is the third installment in a comprehensive State of the Art series
      and aims to evaluate the use of fluoroquinolones in the management of P.
      aeruginosa infection in both children and adults with cystic fibrosis (CF). Oral
      and intravenous ciprofloxacin have been shown to be well-tolerated in the
      treatment of acute pulmonary exacerbations (APE) secondary to P. aeruginosa.
      Older literature supports an oral dosing regimen of 40 mg/kg/day divided every 12
      hr, up to 2 g/day, and intravenous (IV) ciprofloxacin 30 mg/kg/day divided every
      8 hr, maximum 1.2 g/day in children, and 750 mg administered orally twice a day
      or 400 mg IV every 8 hr in adults. However, a recent pharmacodynamic (PD)
      modeling study shows that the literature, U.S. Food and Drug Administration (FDA)
      approved, and Cystic Fibrosis Foundation (CFF) guideline dosing regimens may be
      suboptimal for the treatment of P. aeruginosa in APE. Further study is warranted
      to determine if higher doses of ciprofloxacin are needed. Limited pharmacokinetic
      (PK), PK/PD, and efficacy studies involving levofloxacin exist in adult patients
      with CF. No pediatric data exists for levofloxacin in CF patients. Further study
      is needed to determine the tolerability and efficacy of levofloxacin in APE. At
      this time, the routine use of levofloxacin in the treatment of APE in pediatric
      and adult patients cannot be recommended.

PMID- 22949225
TI  - Activation of coagulation and platelets by candidate membranes of implantable
      devices in a whole blood model without soluble anticoagulant.
AB  - Implantable devices are challenged with thrombus formation at their biomaterial
      interface. Thus the importance of identifying compatible biomaterials that will
      help to improve the performance of these devices are becoming increasingly
      paramount. The aim of this study was to evaluate the activation of coagulation
      and platelets by candidate membranes considered for use in implantable devices on
      the basis of an adapted whole blood model without soluble anticoagulants.
      Evaluated materials were incubated with whole blood without soluble anticoagulant
      in wells coated with heparin. Prothrombin fragment 1+2 (PTF 1+2), thrombin
      antithrombin complex (TAT), and beta-thromboglobulin (BTG) were analyzed in
      plasma samples using enzyme immunoassays. The C5 inhibitor eculizumab was used to
      evaluate the role of complement. Incubation of two of the polyamide membranes PAR
      and PATF led to an increase in concentration of PTF 1+2 and TAT (p < 0.01 for
      PAR, ns for PATF). The BTG concentration was significantly increased for five
      materials [PAR, PATF, polycarbonate (PC), and two polyarylethersulphone membranes
      PAES-1 and PAES-2]. Complement inhibition had no effect on coagulation or
      platelet activation induced by PAR and PATF. In conclusion, PAR and PATF were not
      compatible with blood and should be avoided for use in implantable devices.

PMID- 22949226
TI  - De novo heterozygous desmoplakin mutations leading to Naxos-Carvajal disease.
AB  - STUDY/PRINCIPLES: Arrythmogenic right ventricular cardiomyopathy/dysplasia
      (ARVC/D) is an autosomal-dominantly inherited disease caused by mutations in
      genes encoding desmosomal proteins and is characterised by fibrofatty replacement
      occurring predominantly in the right ventricle and can result in sudden cardiac
      death. Naxos and Carvajal syndrome, autosomal recessive forms of ARVC/D, are
      characterised by involvement of the right and/or left ventricle in association
      with palmoplantar keratoderma and woolly hair. The aim of the present study has
      been to screen for mutations in the desmosomal protein genes of two unrelated
      patients with Naxos-Carvajal syndrome. METHODS AND RESULTS: Desmosomal protein
      genes were screened for mutations by polymerase chain reaction as well as direct
      sequencing approach. In each patient we identified a single heterozygous de novo
      mutation in the desmoplakin gene DSP, p.Leu583Pro and p.Thr564Ile, leading to
      severe combined cardiac/dermatological and cardiac/dermatological/dental
      phenotypes. The DSP missense mutations are localised in the N terminal domain of
      desmoplakin. CONCLUSION: The identified variations in DSP involve highly
      conserved residues. Moreover, the variations are de novo mutations and they are
      localised in critical protein domains that appear to be mutation hot spots. We
      assume that these heterozygous variations are causal for the mixed Naxos-Carvajal
      syndrome phenotype in the screened patients.

PMID- 22949227
TI  - Role of cyclin B1/Cdc2 in mediating Bcl-XL phosphorylation and apoptotic cell
      death following nocodazole-induced mitotic arrest.
AB  - Treatment of cancer cells with microtubule inhibitors causes mitotic arrest,
      which subsequently leads to cell death via activation of the intrinsic apoptotic
      pathway. Mitotically arrested cells typically display increased phosphorylation
      (i.e., inactivation) of two key anti-apoptotic proteins, Bcl-2 and Bcl-XL , but
      the mechanisms that regulate their phosphorylation as well as their role in
      apoptotic cell death following mitotic arrest are still poorly understood at
      present, which are the focus of this study. We recently showed that cyclin B1 and
      cell division cycle 2 (Cdc2) proteins are strongly up-regulated in human breast
      cancer cells following treatment with nocodazole (a prototypical microtubule
      inhibitor), and their up-regulation plays a critical role in the development of
      mitotic prometaphase arrest. In this study, we present evidence showing that the
      up-regulated cyclin B1/Cdc2 complex in nocodazole-treated human breast cancer
      cells is also responsible for the increased phosphorylation of Bcl-2 and Bcl-XL .
      However, only the increased phosphorylation of Bcl-XL , but not the
      phosphorylation of Bcl-2, contributes to subsequent activation of the intrinsic
      cell death pathway. In addition, evidence is presented to show that mitotic
      arrest deficient 2 (MAD2) is a key upstream mediator of the up-regulation of
      cyclin B1/Cdc2 as well as the subsequent increase in phosphorylationof Bcl-2 and
      Bcl-XL in nocodazole-treated cancer cells. Together, these results reveal that
      the up-regulated cyclin B1/Cdc2 complex not only mediates prometaphase arrest in
      nocodazole-treated cells, but also activates the subsequent intrinsic cell death
      pathway in these cells via increased phosphorylation of Bcl-XL .

PMID- 22949228
TI  - Towards a universal method for protein refolding: the trimeric beta barrel
      membrane Omp2a as a test case.
AB  - It has recently been reported that 2-methyl-2,4-pentanediol (MPD) can modulate
      the protein-binding properties of sodium dodecyl sulfate (SDS), turning it into a
      non-denaturing detergent. Indeed both alpha (the lysozyme) and beta (the carbonic
      anhydrase II) soluble enzymes, as well as a beta membrane protein (PagP) have
      been successfully refolded into their native form by using this amphiphatic
      alcohol. In order to support the universal character of our MPD-based technique,
      we have extended its transferability to the Omp2a trimeric membrane porin. The
      far-UV circular dichroism signature of Omp2a refolded with our original procedure
      is identical to that obtained by classical techniques, clearly indicating a
      proper refolding. Moreover, we show that the optimal SDS/MPD ratio for refolding
      Omp2a is similar to what has been observed for other types of proteins. While the
      protocol allows refolding at higher protein concentration (up to 4 mg/mL) and
      ionic strength (up to 1 M NaCl) than other refolding methods, it is also more
      efficient at basic pH values and medium temperature (20-40 degrees C). Finally,
      the key role of the cosolvent was highlighted by a thorough study of the
      efficiency of MPD analogues, and a high variability was observed, as they can be
      able or unable to induce refolding at low or high salt concentrations.

PMID- 22949229
TI  - IGF binding protein-3 mediates stress-induced apoptosis in non-transformed
      mammary epithelial cells.
AB  - Mammary epithelial cell (MEC) number is an important determinant of milk
      production in lactating dairy cows. IGF-I increases IGF binding protein-3 (IGFBP
      3) production in these cells, which plays a role in its ability to enhance
      proliferation. In the present study, we show that the apoptotic factor anisomycin
      (ANS) also increases IGFBP-3 mRNA and protein in a dose- and concentration
      dependent manner that mirrors activation of caspase-3 and -7, with significant
      increases in both IGFBP-3 protein and caspase activation observed by 3 h. Knock
      down of IGFBP-3 with small interfering (si) RNA attenuated the ability of ANS to
      induce apoptosis, while knock-down of IGFBP-2, the other major IGFBP made by
      bovine MEC, had no effect. Reducing IGFBP-3 also decreased the ability of ANS to
      induce mitochondrial cytochrome c release, indicating its involvement in the
      intrinsic apoptotic pathway. In contrast, transfection with IGFBP-3 in the
      absence of ANS failed to induce apoptosis. Since both the mitogen IGF-I and the
      apoptotic inducer ANS increase IGFBP-3 production in MEC, we proposed that
      cellular localization might determine IGFBP-3 action. While both IGF-I and ANS
      stimulated the release of IGFBP-3 into conditioned media, only ANS induced
      nuclear localization of IGFBP-3. A pan-caspase inhibitor had no effect on ANS
      induced nuclear localization of IGFBP-3, indicating that nuclear entry of IGFBP-3
      precedes caspase activation. Treatment with IGF-I had no effect on ANS-induced
      nuclear localization, but did block ANS-induced apoptosis. In summary, our data
      indicate that IGFBP-3 plays a role in stress-induced apoptosis that may require
      nuclear localization in non-transformed MEC.

PMID- 22949230
TI  - Correction of sampling bias in a cross-sectional study of post-surgical
      complications.
AB  - Cross-sectional designs are often used to monitor the proportion of infections
      and other post-surgical complications acquired in hospitals. However,
      conventional methods for estimating incidence proportions when applied to cross
      sectional data may provide estimators that are highly biased, as cross-sectional
      designs tend to include a high proportion of patients with prolonged
      hospitalization. One common solution is to use sampling weights in the analysis,
      which adjust for the sampling bias inherent in a cross-sectional design. The
      current paper describes in detail a method to build weights for a national survey
      of post-surgical complications conducted in Israel. We use the weights to
      estimate the probability of surgical site infections following colon resection,
      and validate the results of the weighted analysis by comparing them with those
      obtained from a parallel study with a historically prospective design.

PMID- 22949231
TI  - Preventive and curative effects of radon inhalation on chronic constriction
      injury-induced neuropathic pain in mice.
AB  - BACKGROUND: Radon therapy is clinically useful for the treatment of pain-related
      diseases. However, there have been no studies regarding the effects of radon
      inhalation on neuropathic pain. In this study, we aimed to determine whether
      radon inhalation actually induced a remission of neuropathic pain and improved
      the quality of life. METHODS: First, we investigated the antinociceptive effects
      of radon inhalation in the chronic constriction injury (CCI) model of neuropathic
      pain. We evaluated pain behaviour in mice before and after CCI surgery, using von
      Frey test. Pretreated mice received CCI surgery immediately after 24-h inhalation
      of radon at background (BG) concentration (c. 19 Bq/m(3) ), or at a concentration
      of 1000 or 2000 Bq/m(3) , and post-treated mice inhaled similar levels of radon 2
      days after CCI surgery. RESULTS: CCI surgery induced mechanical allodynia and
      hyperalgesia on a plantar surface of mice, as assessed using von Frey test, and
      2000 Bq/m(3) radon inhalation alleviated hyperalgesic conditions 22-37% compared
      to BG level concentration. Concurrently, CCI surgery increased norepinephrine
      (NE), tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO)
      concentrations in plasma, and leukocyte migration in paws. Furthermore, CCI
      induced neuropathy reduced superoxide dismutase (SOD) activity. Treatment with
      radon inhalation, specifically at a concentration of 2000 Bq/m(3) , produced
      antinociceptive effects, i.e., lowered plasma TNF-alpha, NE and NO levels and
      restored SOD activity, as well as pain-related behaviour. CONCLUSIONS: This study
      showed that inhalation of 2000 Bq/m(3) radon prevented and alleviated CCI-induced
      neuropathic pain in mice.

PMID- 22949232
TI  - Isolation and screening of heavy metal resistant bacteria from wastewater: a
      study of heavy metal co-resistance and antibiotics resistance.
AB  - The uncontrolled discharges of wastes containing a large quantity of heavy metal
      create huge economical and healthcare burdens particularly for people living near
      that area. However, the bioremediation of metal pollutants from wastewater using
      metal-resistant bacteria is a very important aspect of environmental
      biotechnology. In this study, 13 heavy metal resistant bacteria were isolated
      from the wastewater of wadi El Harrach in the east of Algiers and characterized.
      These include zinc-, lead-, chromium- and cadmium-resistant bacteria. The metal
      resistant isolates characterized include both Gram-negative (77%) and Gram
      positive (23%) bacteria. The Minimum Inhibitory Concentration (MIC) of wastewater
      isolates against the four heavy metals was determined in solid media and ranged
      from 100 to 1,500 MUg/ml. All the isolates showed co-resistance to other heavy
      metals and antibiotic resistance of which 15% were resistant to one antibiotic
      and 85% were multi- and bi-antibiotics resistant. The zinc-resistant species
      Micrococcus luteus was the much more heavy metal resistant. The results of
      toxicity tests on Vibrio fischeri showed that the DI(50) (5 min) as low as 0.1
      carried away luminescence inhibition greater than 50%.

PMID- 22949233
TI  - How reliable are odour assessments?
AB  - This paper will demonstrate the differences found in odour test results, when
      odour sampling is performed at the same sources by two different consultants. By
      examining two case studies, this paper will highlight that the difference between
      the results can be significant. Both studies are based on odour sampling programs
      determining the odour removal efficiency of odour control units installed at two
      different facilities: a pet food facility and an oil/grease recycling facility.
      The first study is based on odour measurements at the inlet and outlet of the
      unit installed by Applied Plasma Physics AS at the pet food facility. Odour
      assessments were performed by two separate consultants at the same time. The
      second study is based on testing of the odour removal effectiveness of two units:
      a scrubber and a biofilter at an oil/grease recycling facility. During this study
      two odour sampling programs were performed by two consultants at different times,
      but under the same process conditions. This paper will show how varying results
      can play a role in choosing the adequate odour control technologies. The final
      results suggest that although, an odour control unit may appear to be
      insufficient, it actually is successful at removing the odours.

PMID- 22949234
TI  - The role of MBR technology for the improvement of environmental footprint of
      wastewater treatment.
AB  - This paper aims to demonstrate the relevance of membrane bioreactor (MBR)
      technology for the reduction of the environmental footprint of wastewater
      treatment in terms of removal of microbial and organic trace pollutants with
      increased reliability of operation. The application of a holistic approach using
      failure mode analysis, life cycle analysis (LCA), water quality fingerprints and
      environmental impacts underlines the lower environmental footprint of MBRs
      compared with conventional activated sludge. Several elements of this empirical
      approach can be included to upgrade the existing LCA tools in order to include
      the reduction of eco-toxicity, better human health protection and water reuse.

PMID- 22949235
TI  - Enumeration of viable Escherichia coli by real-time PCR with propidium monoazide.
AB  - A photo-inducible DNA-binding dye, propidium monoazide (PMA), was used to
      distinguish viable and dead Escherichia coli cells. Microscopic observations
      using a combination of the dyes 4',6-diamidino-2-phenylindole and PMA indicated
      that PMA stained only dead cells, with membrane damage, red. Mixtures of viable
      and heat-treated E. coli cells were subjected to real-time polymerase chain
      reaction (PCR) with PMA treatment. Viable cell counts were linearly related to
      real-time PCR threshold cycle values for PMA-treated cells in the mixtures of
      viable and heat-treated cells, as long as the ratio of dead cells to viable cells
      was no greater than 10. In the wastewater treatment plants, total, viable and
      culturable E. coli were enumerated by real-time PCR, real-time PCR coupled with
      PMA treatment and the most probable number method using EC-MUG medium,
      respectively. The concentrations of viable E. coli in the wastewater treatment
      plants were much higher than those of culturable cells. In addition, viable cells
      were even more chlorine resistant than culturable ones.

PMID- 22949236
TI  - Study of antifouling modified ultrafiltration membrane based on the secondary
      treated water of urban sewage.
AB  - Mixtures of polyvinylidene fluoride (PVDF) and polyvinyl alcohol (PVA) containing
      hydrophilic ultrafiltration membranes were prepared by adding PVA (5 to 30%) to
      PVDF by the phase inversion method. The hydrophilic contact angle (CA),
      equilibrium water content, pure water flux and bovine serum albumin retention
      were studied to assess the membrane performance. The anti-fouling performance of
      modified membrane to the secondary treated water was evaluated by flux decline,
      washing recovery rate and fouling resistance analysis. Scanning electron
      microscopy showed that the cross-section structure of the membranes had finger
      like pores, which were well developed and uniformly distributed, and the sub
      layer structure was looser and more porous with the increasing content of PVA.
      The CA gradually decreased. The steady flux was 800 L/m(2) h from P15 to P30, and
      the BSA retention sharply declined. The ultrafiltration tests for secondary
      treated water indicated that the main fouling source of the modified membrane was
      the concentration polarization and cake layer resistance. After physical
      flushing, the flux recovery ratio of the membrane could reach 100% when the PVA
      content was 5-15%, which shows excellent anti-pollution performance and good
      prospects for use in processing wastewater from urban sewage.

PMID- 22949237
TI  - Seawater injection barrier recharge with advanced reclaimed water at Llobregat
      delta aquifer (Spain).
AB  - The main aquifer of the Llobregat delta (Barcelona, Spain) has been affected by
      seawater intrusion since the 1960s. The Catalan Water Agency (ACA) has sponsored
      the construction of a positive hydraulic barrier in order to stop the progress of
      seawater intrusion advance due to the intensive aquifer development. The
      hydraulic barrier consists of 15 wells into which highly treated reclaimed water
      from the waste water treatment plant of the Baix Llobregat is injected. Water is
      subjected, prior to the distribution to the injection wells, to secondary and
      tertiary treatments, and later to ultrafiltration, UV disinfection without
      chlorination, and salinity reduction through reverse osmosis. A preliminary pilot
      phase of the project was started in late 2007, with highly positive results, and
      the second phase started in mid 2010. Hydrogeological and hydrochemical
      monitoring data indicate an efficient performance and aquifer improvement. The
      evaluation of such efficiency and operational costs has been analyzed and
      discussed.

PMID- 22949238
TI  - A fuzzy inference method based on association rule analysis with application to
      river flood forecasting.
AB  - In this paper, a computationally efficient version of the widely used Takagi
      Sugeno (T-S) fuzzy reasoning method is proposed, and applied to river flood
      forecasting. It is well known that the number of fuzzy rules of traditional fuzzy
      reasoning methods exponentially increases as the number of input parameters
      increases, often causing prohibitive computational burden. The proposed method
      greatly reduces the number of fuzzy rules by making use of the association rule
      analysis on historical data, and therefore achieves computational efficiency for
      the cases of a large number of input parameters. In the end, we apply this new
      method to a case study of river flood forecasting, which demonstrates that the
      proposed fuzzy reasoning engine can achieve better prediction accuracy than the
      widely used Muskingum-Cunge scheme.

PMID- 22949239
TI  - Application of a simulated annealing optimization to a physically based erosion
      model.
AB  - A major risk concerning the calibration of physically based erosion models has
      been partly attributable to the lack of robust optimization tools. This paper
      presents the essential concepts and application to optimize the erosion
      parameters of an erosion model using data collected in an experimental basin,
      with a global optimization method known as simulated annealing (SA) which is
      suitable for solving optimization problems of large scales. The physically based
      erosion model that was chosen to be optimized here is the Watershed Erosion
      Simulation Program (WESP), which was developed for small basins to generate the
      hydrograph and the respective sedigraph. The field data were collected in an
      experimental basin located in a semiarid region of Brazil. On the basis of these
      results, the following erosion parameters were optimized: the soil moisture
      tension parameter (N(s)) that depends also on the initial moisture content, the
      channel erosion parameter (a), the soil detachability factor (K(R)), and the
      sediment entrainment parameter by rainfall impact (K(I)), whose values could
      serve as initial estimates for semiarid regions within northeastern Brazil.

PMID- 22949240
TI  - Effect of chemical and biological factors on the densification of filamentous
      sludge.
AB  - Densification may be an alternative method for controlling sludge bulking;
      however, little information is available on the method. Various methods including
      different oxygen concentrations, surface velocities of aeration, calcium
      concentrations and extended starvation period were employed for triggering
      densification of filamentous sludge in this study. It was found that high surface
      velocity of aeration could effectively improve the settleability of filamentous
      sludge in the short term, which resulted in filamentous granulation, but could
      not avoid filamentous bulking even after granulation. Increase of calcium
      concentration could also improve the settleability by forming pigtail filaments
      colony in the short term, but could not trigger granulation. Extension of
      starvation period seems effective neither for further densification nor for
      granulation. Additionally, increased ovality of meshes formed by filaments was
      frequently associated with a dense structure of filamentous sludge. It was
      suggested that pigtail type of filamentous colony that thus increased the
      resistance to elevated shear force may encourage the densification of sludge, and
      two kind of densification growth patterns, i.e., granular or cluster growth
      pattern of filamentous sludge, were identified.

PMID- 22949241
TI  - Removal of micropollutants in municipal wastewater treatment plants by powder
      activated carbon.
AB  - Micropollutants (MP) are only partly removed from municipal wastewater by
      nutrient removal plants and are seen increasingly as a threat to aquatic
      ecosystems and to the safety of drinking water resources. The addition of powder
      activated carbon (PAC) is a promising technology to complement municipal nutrient
      removal plants in order to achieve a significant reduction of MPs and ecotoxicity
      in receiving waters. This paper presents the salient outcomes of pilot- and full
      scale applications of PAC addition in different flow schemes for micropollutant
      removal in municipal wastewater treatment plants (WWTPs). The sorption efficiency
      of PAC is reduced with increasing dissolved organic carbon (DOC). Adequate
      treatment of secondary effluent with 5-10 g DOC m(-3) requires 10-20 g PAC m(-3)
      of effluent. Counter-current use of PAC by recycling waste PAC from post
      treatment in a contact tank with an additional clarifier to the biology tank
      improved the overall MP removal by 10 to 50% compared with effluent PAC
      application alone. A dosage of 15 g PAC m(-3) to a full-scale flocculation sand
      filtration system and recycling the backwash water to the biology tank showed
      similar MP elimination. Due to an adequate mixing regime and the addition of
      adapted flocculants, a good retention of the fine fraction of the PAC in the deep
      bed filter were observed (1-3 g TSS m(-3); TSS: total suspended solids). With
      double use of PAC, only half of the PAC was required to reach MP removal
      efficiencies similar to the direct single dosage of PAC to the biology tank.
      Overall, the application of PAC in WWTPs seems to be an adequate and feasible
      technology for efficient MP elimination (>80%) from wastewater comparable with
      post ozonation.

PMID- 22949242
TI  - Surface characterisation of biofouled NF membranes: role of surface energy for
      improved rejection predictions.
AB  - Biomass attachment and growth on high pressure membranes alter the surface
      characteristics and rejection performance of nanofiltration membranes. Along with
      electrostatic interaction and size exclusion, hydrophobic interaction between
      solutes and membrane surface play the major role in the separation process.
      Therefore, in attempt to properly quantify the surface energy of clean and
      biofouled membranes, different contact angle techniques were applied in this
      research. The surface energies of membranes were determined on dry, wet and
      hydrated surfaces. Results indicate that drying of the membrane surface leads to
      a modification of the surface properties, which are therefore not representative
      of the membrane in its operational conditions. Immersing the membrane in water
      resulted in detachment of biomass material into the surrounding liquid, thus
      hampering a correct estimation of the contact angle. Contact angle measurements
      on hydrated surfaces, on the contrary, produced reproducible results, which are
      consistent with current knowledge. In addition, when the values obtained by
      hydrated method were applied in a predictive model earlier developed, a
      significant improvement in predictions resulted.

PMID- 22949244
TI  - Purification of eutrophic water by ryegrass.
AB  - The present study was carried out to investigate the growth characteristics of
      different ryegrass (Lolium perenne L.) cultivars and their ability to remediate
      eutrophic water using floating plant-bed technology. Greenhouse and lake
      experiments were conducted to evaluate the grass genotypes for water remediation.
      Twelve cultivars of ryegrass including Grazer, Secale Cerale, Energa, Rustmaster,
      AngusI, Abundant, AngusII, Jivet, Gulf, Surrey, Major and Barwoltra were grown in
      the floating plant-bed system. The plant biomass, plant NP (nitrogen and
      phosphorus) accumulations and the water purification capacity of selected grasses
      were significantly different (P < 0.05). Abundant, AngusII and Major showed most
      efficient purification capacity of eutrophic water. In a greenhouse, after 26
      days of growth, the eutrophic water was purified to various extents by the
      different ryegrass cultivars. Nitrogen removal efficiency varied from 52.20% to
      73.82% and phosphorus removal efficiency ranged from 75.12% to 84.77%. In a lake
      experiment at Huajiachi pond, after 162 days of growth, the plant shoot biomass
      increased from 321.5 to 922.8 g/m(2) dry weight basis, shoot NP accumulation
      ranged from 61.5 to 168.2 mg m(-2) d(-1) and 11.9 to 47.2 mg m(-2) d(-1)
      respectively. NP accumulation rate by the various cultivars of ryegrass was
      highly positively correlated to their biomass production and water purification
      capacity. Thus, plant biomass could be used as an indicator for assessing
      purification capacity of a ryegrass cultivar.

PMID- 22949243
TI  - Engineered ecosystem for on-site wastewater treatment in tropical areas.
AB  - There is a worldwide demand for decentralized wastewater treatment options. An on
      site engineered ecosystem (EE) treatment plant was designed with a multistage
      approach for small wastewater generators in tropical areas. The array of
      treatment units included a septic tank, a submersed aerated filter, and a
      secondary decanter followed by three vegetated tanks containing aquatic
      macrophytes intercalated with one tank of algae. During 11 months of operation
      with a flow rate of 52 L h(-1), the system removed on average 93.2% and 92.9% of
      the chemical oxygen demand (COD) and volatile suspended solids (VSS) reaching
      final concentrations of 36.3 +/- 12.7 and 13.7 +/- 4.2 mg L(-1), respectively.
      Regarding ammonia-N (NH(4)-N) and total phosphorus (TP), the system removed on
      average 69.8% and 54.5% with final concentrations of 18.8 +/- 9.3 and 14.0 +/-
      2.5 mg L(-1), respectively. The tanks with algae and macrophytes together
      contributed to the overall nutrient removal with 33.6% for NH(4)-N and 26.4% for
      TP. The final concentrations for all parameters except TP met the discharge
      threshold limits established by Brazilian and EU legislation. The EE was
      considered appropriate for the purpose for which it was created.

PMID- 22949245
TI  - Effect of substrates and intermediate compounds on foaming in manure digestion
      systems.
AB  - Manure contains several compounds that can potentially cause foaming during
      anaerobic digestion. Understanding the effect of substrates and intermediate
      compounds on foaming tendency and stability could facilitate strategies for
      foaming prevention and recovery of the process. In this study, the effect of
      physicochemical properties of substrates and intermediate compounds on liquid
      properties such as surface tension, surfactant property, and hydrophobicity were
      investigated and compared with the effect on foaming tendency and foam stability.
      The results showed that there was no consistent correlation between foaming
      potential and hydrophobicity, oil displacement area (ODA) or surface tension of
      the tested solutions, and the best way to determine the foaming property of the
      solution was to directly measure foaming tendency and foam stability. Na-oleate
      and acetic acid showed the highest potential to create foam in a manure digester.
      Moreover, high organic loading of lipids and protein, and high concentrations of
      acetic and butyric acids also showed a strong tendency to create foaming during
      anaerobic digestion. Due to their great ability to stabilize foam, high organic
      loadings of Na-oleate or gelatine were considered to be the main potential
      foaming problem.

PMID- 22949246
TI  - Revealing microbial community structures in large- and small-scale activated
      sludge systems by barcoded pyrosequencing of 16S rRNA gene.
AB  - The diversity of bacterial groups in activated sludge from large- and small-scale
      wastewater treatment plants was explored by barcoded pyrosequencing of 16S rRNA
      gene. Activated sludge samples (three small and 17 large scale) were collected
      from 12 wastewater treatment plants to clarify precise taxonomy and relative
      abundances. DNA was extracted, and amplified by 4 base barcoded 27f/519r primer
      set. The 454 Titanium (Roche) pyrosequences were obtained and analyses performed
      by Quantitative Insight Into Microbial Ecology (QIIME) with around 100,000 reads.
      Sequence statistics were computed, while constructing a phylogenetic tree and
      heatmap. Computed results explained total microbial diversity at phylum and class
      level and resolution was further extended to Operational Taxonomic Unit (OTU)
      based taxonomic assignment for investigating community distribution based on
      individual sample. Composition of sequence reads were compared and microbial
      community structures for large- and small-scale treatment plants were identified
      as major phyla (Proteobacteria and Bacteroidetes) and classes (Betaproteobacteria
      and Bacteroidetes). Also, family level breakdowns were explained and differences
      in family Nitrospiraceae and phylum Actinobacteria found at their species level
      were also illustrated. Thus, the pyrosequencing method provides high resolution
      insight into microbial community structures in activated sludge that might have
      been unnoticed with conventional approaches.

PMID- 22949247
TI  - A groundwater perspective on the river basin management plan for central Portugal
      - developing a methodology to assess the potential impact of N fertilizers on
      groundwater bodies.
AB  - The Water Framework Directive establishes that the river basin management plans
      must have a summary of the pressures and impacts of human activities, such as
      agriculture, on the chemical and quantitative status of groundwater bodies. In
      order to identify those areas where a potential impact from agricultural
      activities on groundwater bodies exists, but currently lacking groundwater
      monitoring data, a methodology was developed that combines the use of gross
      nitrogen balance values with the results of a specific vulnerability assessment
      index. A farm management efficiency parameter is added, to identify the factors
      that contribute to nitrogen use efficiency and to assess the near-future
      scenarios. This methodology allows the identification of significant pressures
      that may be responsible for a groundwater body failing good status where there is
      no representative monitoring network.

PMID- 22949248
TI  - Flow and sediment yield simulations for Bukit Merah Reservoir catchment,
      Malaysia: a case study.
AB  - Bukit Merah Reservoir is the main potable and irrigation water source for Kerian
      District, Perak State, Malaysia. For the past two decades, the reservoir has
      experienced water stress. Land-use activities have been identified as the
      contributor of the sedimentation. The Soil and Water Assessment Tool (SWAT) was
      used to simulate and quantify the impacts of land-use change in the reservoir
      watershed. The SWAT was calibrated and two scenarios were constructed
      representing projected land use in the year 2015 and hypothetical land use to
      represent extensive land-use change in the catchment area. The simulation results
      based on 17 years of rainfall records indicate that average water quantity will
      not be significantly affected but the ground water storage will decrease and
      suspended sediment will increase. Ground water decrease and sediment yield
      increase will exacerbate the Bukit Merah Reservoir operation problem.

PMID- 22949249
TI  - Bioremoval of textile dyes with different chemical structures by Aspergillus
      versicolor in molasses medium.
AB  - Bioremoval of 17 dyes with different chemical structures by Aspergillus
      versicolor was detected in this study. Maxilon Red GRL (MR-GRL), Everdirect Fast
      Black VSF (EFB-VSF) and Brillant Blue R (BB-R) were removed better by fungal
      mycelia. Optimum pH values were found as 6 for all three dyes. In further
      experiments in the highest dye concentrations tested in this study, 58.3, 100 and
      49% removal yields and 14.8, 12.6, 9.0 q(m) values were found for MR-GRL, EFB-VSF
      and BB-R, respectively. Chemical oxygen demand (COD) reduction after seven days
      of incubation period and role of laccase activity of Aspergillus sp. were also
      investigated. COD reduction and laccase activities were 55.6% and 2.93 U/mL for
      MR-GRL, 90.7% and 3.0 U/mL for EFB-VSF and 69.0% and 1.79 U/mL for BB-R,
      respectively. According to these results A. versicolor deserves notable attention
      for removal of these dyes in wastewater effluents.

PMID- 22949250
TI  - Survey on production quality of electrodialysis reversal and reverse osmosis on
      municipal wastewater desalination.
AB  - Water shortage has become an emerging environmental issue. Reclamation of the
      effluent from municipal wastewater treatment plant (WWTP) is feasible for meeting
      the growth of water requirement from industries. In this study, the results of a
      pilot-plant setting in Futian wastewater treatment plant (Taichung, Taiwan) were
      presented. Two processes, sand filter - ultrafiltration - reverse osmosis (SF-UF
      RO) and sand filter - electrodialysis reversal (SF-EDR), were operated in
      parallel to evaluate their stability and filtrate quality. It has been noticed
      that EDR could accept inflow with worse quality and thus required less
      pretreatment compared with RO. During the operation, EDR required more frequent
      chemical cleaning (every 3 weeks) than RO did (every 3 months). For the filtrate
      quality, the desalination efficiency of SF-EDR ranged from 75 to 80% in
      continuous operation mode, while the conductivity ranged from 100 to 120 MUS/cm,
      with turbidity at 0.8 NTU and total organic carbon at 1.3 mg/L. SF-EDR was less
      efficient in desalinating the multivalent ions than SF-UF-RO was. However for the
      monovalent ions, the performances of the two processes were similar to each
      other. Noticeably, total trihalomethanes in SF-EDR filtrate was lower than that
      of SF-UF-RO, probably because the polarization effects formed on the concentrated
      side of the EDR membrane were not significant. At the end of this study, cost
      analysis was also conducted to compare the capital requirement of building a full
      scale wastewater reclamation plant using the two processes. The results showed
      that using SF-EDR may cost less than using SF-UF-RO, if the users were to accept
      the filtrate quality of SF-EDR.

PMID- 22949251
TI  - Occurrence of micro-organic pollutants on phosphorus recovery from urine.
AB  - Increased population growth and food prices have resulted in more demand for
      fertilizers, especially phosphorus (P), to be used in agriculture and production
      of food crops. Phosphorus is one of the important natural resources and will be
      exhausted in the near future. Nowadays, struvite production is a good method to
      recover P from urine. However, the natural urines contain high amounts of micro
      organic pollutants which may cause health risks. Therefore, in this contribution,
      we investigated the amount of micro-organic pollutants in struvite from urine.
      There are various kinds of pharmaceuticals and hormones which are used in the
      world. Nevertheless, we focused on 10 pharmaceuticals (amoxycillin,
      carbamazepine, erythromycin, furosemide, atenolol, ibuprofen, norfloxacin,
      trimethoprim, tetracycline, and acetylsalicylic acid) and one hormone (17beta
      estradiol) as representatives. The experiments were carried out with synthetic
      and natural urines. After the production of struvite, the results from synthetic
      and natural urine samples showed that only tetracycline, erythromycin, and
      norfloxacin remained in the struvite, and, especially, tetracycline remained in
      struvite with quite a high amount.

PMID- 22949252
TI  - Biodegradation of bisphenol A and 4-alkylphenols by Novosphingobium sp. strain
      TYA-1 and its potential for treatment of polluted water.
AB  - We investigated the use of Novosphingobium sp. strain TYA-1 for the simultaneous
      removal of bisphenol A (BPA) and 4-alkylphenols (4-APs) from complex polluted
      waters. Strain TYA-1 degraded BPA and utilized it as a sole carbon and energy
      source via oxidative skeletal rearrangement involving the cytochrome p450
      monooxygenase system. Strain TYA-1 also degraded 4-APs with branched side alkyl
      chains (4-tert-butylphenol [4-tert-BP], 4-sec-butylphenol, 4-tert-pentylphenol, 4
      tert-octylphenol [4-tert-OP], and branched nonylphenol mixture) via 4
      alkylcatechols but could not degrade 4-APs with linear side alkyl chains.
      Degradation of 4-APs, like that of BPA, involved the cytochrome p450
      monooxygenase system in strain TYA-1. A sequencing batch bioreactor (100 mL of
      polluted water [50 mg/L BPA, 50 mg/L 4-tert-BP, and 5 mg/L 4-tert-OP]; 6 h of
      reaction time/cycle; 12 cycles in total) containing alginate-immobilized TYA-1
      cells (15 mg dry cells) simultaneously removed BPA, 4-tert-BP, and 4-tert-OP from
      complex polluted waters. These immobilized TYA-1 cells could be reused for a
      total of 9 cycles without any loss of degradation activity. Our results support
      the potential of using immobilized TYA-1 cells for the simultaneous removal of
      BPA and 4-APs from complex polluted waters.

PMID- 22949253
TI  - Quantum efficiencies of the photo-Fenton degradation of atrazine in water.
AB  - An experimental work in a well-stirred batch recycling reactor for the photo
      Fenton degradation of atrazine in water is presented. A study of the quantum
      efficiency is performed to assess the effectiveness of the photo-Fenton process
      on the atrazine degradation and total organic carbon (TOC) mineralization.
      Apparent and absolute quantum efficiencies of degradation and mineralization of
      an atrazine-based commercial herbicide are determined under different
      experimental conditions. Higher apparent efficiencies were found for both
      atrazine degradation and TOC mineralization when the ferric ion and hydrogen
      peroxide concentrations are increased. Because of the well known stability of the
      triazine ring, atrazine was not completely mineralized by the photo-Fenton
      process. However, a TOC reduction of 40% was achieved, being 62.5% of the maximum
      value that can be reached.

PMID- 22949254
TI  - Biodegradability and methane production potential of glycerol generated by
      biodiesel industry.
AB  - Crude glycerol, the main by-product of the biodiesel industry, is a material
      containing compounds considered recalcitrant to microorganisms. The aims of this
      study were to determine the anaerobic biodegradability and the methane production
      potential (MPP) of different crude glycerols generated from the
      transesterification of oils from several kinds of seeds and/or beans, and the
      anaerobic toxicity of crude glycerol obtained from a mixture of soybean and
      cottonseed oils. All tests were based on specific methanogenic activity assays
      (SMA). The biodegradability tests and the MPP assays lasted 30 days. Toxicity was
      evaluated through the statistical technique of factorial design and a response
      surface was generated in which the concentrations of crude glycerol and glucose
      were the independent variables and SMA was the dependent variable. The results
      showed that the type of seed or bean, as well as the transesterification process,
      affected the anaerobic biodegradability. Biodegradability ranged between 65.9 and
      85.6% and MPP, between 0.220 and 0.322 m(3) CH(4)/kg crude glycerol. The toxicity
      test showed that crude glycerol was not toxic to anaerobic sludge.

PMID- 22949255
TI  - Impact assessment of odours emitted by a wastewater treatment plant.
AB  - Complaints from the Domingos Martins population about sewage odours in the city
      made the district attorney order an impact assessment of the odours emitted by
      the city wastewater treatment plant (WWTP). This study comprised various
      techniques, models and population surveys. In 2007, an odour emission model
      proved that the main hydrogen sulphide emitter was the aeration tank of the WWTP
      (13.5 g h(-1)) and such emissions, according to CALPUFF model, should be
      perceived in the whole Domingos Martins city centre area. In this area, 58% of
      those interviewed were annoyed by the WWTP odours. However, in 2009, the odour
      monitoring panel recorded few odour occurrences. A second population survey
      showed that hereafter only 20% of those interviewed were annoyed by the WWTP
      emissions. Odour emission and dispersion models run with 2010 data proved a
      drastic reduction of the WWTP aeration tank emissions and consequently the city
      centre was not bothered by WWTP emissions anymore. The odour emission reduction
      was due to the modification of the WWTP aeration tank system. Despite the odour
      emission reduction, houses located southeast of the WWTP were still annoyed by
      sewage odours. However, in this part of the town, other sources of sewage odours
      have been found.

PMID- 22949256
TI  - Optimization of the removal of phenol by soybean seed coats using response
      surface methodology.
AB  - Peroxidase from soybean seed coats catalyzes the oxidation and polymerization of
      aromatic compounds in the presence of H(2)O(2). The present study investigated
      the optimization of the phenol removal from wastewaters by direct using of
      soybean seed coats that can be extended to large scale, as a cost-effective
      option in comparison to pure enzyme. A central composite design was used to
      evaluate the effect of the following factors on the phenol removal: H(2)O(2)
      concentration (1-40 mmol/L), polyethylene glycol (PEG) concentration (0-1 g/L)
      and the amount of soybean seed coats (10-60 g/L). The results showed that PEG
      concentration had no significant effect on phenol conversion. Additionally, by
      increasing the amount of soybean seed coats, the extent of phenol conversion was
      increased and a higher concentration of H(2)O(2) was required to reach the
      maximum phenol conversion. Under optimum conditions for 1 mmol/L initial phenol,
      50 g/L soybean seed coats, 14 mmol/L H(2)O(2) and 0.8 g/L PEG, the phenol
      conversion after 30 min was 78%. After 2 h, the catalyzed process was capable of
      achieving 90-92% removal of the total phenol from synthetic wastewater. A cubic
      model was also developed that was verified by predicting some independent
      experimental results.

PMID- 22949257
TI  - Effect of the addition of fatty by-products from the refining of vegetable oil on
      methane production in co-digestion.
AB  - The purpose of this work was to investigate the effects of the addition of by
      products from the refining of vegetable oil on the behavior of co-digestion
      reactors treating a mixture of grass, cow dung and fruit and vegetable waste.
      Three by-products were used: one soapstock, one used winterization earth and one
      skimming of aeroflotation of the effluents. Three 15 l reactors were run in
      parallel and fed five times a week. In a first phase of 4 weeks, the three
      reactors were fed with the co-digestion substrates alone (grass, cow dung and
      fruit and vegetable waste) at an organic loading rate (OLR) of 1.5 g VS/kg d (VS:
      volatile solids). Then, a different by-product from the refining of oil was added
      to the feed of each reactor at an OLR of 0.5 g VS/kg d, generating a 33% increase
      in the OLR. The results show that the addition of by-products from the refining
      of oil is an efficient way of increasing the methane production of co-digestion
      reactors thanks to high methane yield of such by-products (0.69-0.77 l CH(4)/g VS
      loaded). In fact, in this work, it was possible to raise the methane production
      of the reactors by about 60% through a 33% increase in the OLR thanks to the
      addition of the by-products from the refining of vegetable oil.

PMID- 22949258
TI  - Enhanced denitrification with external carbon sources in a biological anoxic
      filter.
AB  - Three parallel biological anoxic filters (BaFs) were operated to investigate the
      denitrification kinetics of methanol, brewery wastewater and bakery wastewater.
      The experiment was conducted within the temperature range of 15-20  degrees C,
      with an influent nitrate and carbon dosage of 30 mg/L and 150 mg COD/L (COD:
      chemical oxygen demand). The denitrification efficiencies of brewery wastewater,
      bakery wastewater and methanol were 84, 66 and 74%, specific denitrification
      rates were 1.44, 1.11 and 1.24 kg NO(3)-N/m(3) d, and total nitrogen (TN) removal
      rates were 74, 62 and 66%, respectively. The volatile attached solid (VAS) tests
      reveal that methanol has the minimum net biomass yield, so it needs the least
      carbon to nitrogen (expressed in COD to nitrate, C/N) ratio for complete
      denitrification. While the brewery wastewater and bakery wastewater need higher
      C/N ratio to remove all nitrate nitrogen, and they both may need pretreatment to
      remove phosphate when used as external carbon sources.

PMID- 22949259
TI  - The use of a range of ultrasound frequencies to reduce colouration caused by
      dyes.
AB  - The formation of hydrogen peroxide and the degree of decolourisation of six
      different dyes as a result of sonication over several ultrasonic frequencies (20,
      40, 380, 512, 850, 1,000 and 1,176 kHz) was investigated and correlated. It was
      found that the highest levels of hydrogen peroxide and also the greatest amount
      of decolourisation occurred at 850 kHz. 380 and 512 kHz also resulted in some
      decolourisation, however higher and lower ultrasonic frequencies were not
      effective.

PMID- 22949260
TI  - The role of the headspace in hydrogen sulfide removal during microaerobic
      digestion of sludge.
AB  - The role of the headspace (HS) in the microaerobic removal of hydrogen sulfide
      from biogas produced during sludge digestion was studied. Research was carried
      out in a pilot reactor with a total volume of 265 L, under mesophilic conditions.
      Biogas was successfully desulfurized (99%) by introducing pure oxygen (0.46
      NL/L(fed)) into the recirculation stream when the HS volume was both 50.0 and 9.5
      L. The removal efficacy dropped sharply to ~15% when the HS was reduced to 1.5 L.
      The system responded quickly to the operational changes imposed: micro
      oxygenation stops and variations in supply, as well as HS volume reductions and
      increases. As the final result, the microaerobic process required a minimum
      surface into the gas space to occur, which along with the elemental sulfur
      deposition in this area indicated that the oxidation took place there.
      Additionally, the pattern of sulfur accumulation suggested that the removal
      occurred preferentially on certain materials, and pointed to a significant
      biological contribution.

PMID- 22949261
TI  - Gas pockets in a wastewater rising main: a case study.
AB  - This paper presents a case study of an existing wastewater rising main (WWRM) in
      which an extreme transient event produced by simultaneous power failure of the
      pumps caused the rupture of a 1.2 m (48 in) prestressed concrete cylinder pipe
      (PCCP), causing an important leakage of sewage. The event and the methodology
      followed in order to validate the diagnostics of the failure are described. The
      detail study included in situ observation of the system, experimental
      investigation in a setup, hydraulic analysis, as well as details of the
      structural strength of the WWRM. After the extensive investigation and several
      simulations of fluid transients for different scenarios and flow conditions, it
      was found that stationary small gas pockets accumulated at high points of the
      WWRM were identified as the principal contributory factor of the failure. This
      case study serves as clear warning of the consequences of operating a WWRM with
      gas pockets at its high points.

PMID- 22949263
TI  - Characterization of drug-protein interactions by capillary electrophoresis
      hyphenated to mass spectrometry.
AB  - The demand for analytical techniques to evaluate and measure drug-plasma protein
      interactions continues to increase. The binding of drugs to plasma proteins is an
      important parameter to determine during the drug development process because it
      impacts both pharmacokinetics and pharmacodynamics. Among the numerous methods
      that have been proposed to perform such studies, CE in frontal analysis mode
      (CE/FA) is attractive because it consumes a relatively low amount of samples, is
      fast, and enables analyses under near-physiological conditions. Most CE/FA
      applications have been performed with UV detection and often lack sensitivity. In
      this study, CE was hyphenated to MS to enhance the sensitivity of the method and
      to evaluate strong drug-plasma protein interactions. To adapt the previously
      developed CE/FA-UV method to CE/FA-MS, different parameters were considered, such
      as the buffer composition, the rinsing step, and the ESI and MS parameters. The
      most critical aspect involved obtaining stable MS signals. Good results were
      achieved due to careful optimization of the ESI and MS parameters, among which
      the sheath liquid composition appeared to be the most significant. Interactions
      between six drugs and alpha(1) -acid glycoprotein and three drugs and BSA,
      including basic, neutral, and acidic drugs, were measured with the optimized
      CE/FA-MS method. The obtained affinity constants ranged from 1.10(-4)  M(-1)  to
      2.10(-5)  M(-1)  and were in good agreement with the results that were obtained
      by CE/FA-UV and equilibrium dialysis.

PMID- 22949264
TI  - Reply: To PMID 22744978.

PMID- 22949265
TI  - Enhanced production of Aspergillus niger laccase-like multicopper oxidases
      through mRNA optimization of the glucoamylase expression system.
AB  - In filamentous fungi, most of the strategies used for the improvement of protein
      yields have been based on an increase in the transcript levels of a target gene.
      Strategies focusing at the translational level have been also described, but are
      far less explored. Here the 5' untranslated sequence of the glaA mRNA, a widely
      used expression system for the expression of recombinant proteins, was modified
      by the introduction of different nucleotide elements that have positive role in
      the translation process. Five Aspergillus niger laccase-like multicopper oxidases
      (MCOs) coding genes were fused to the native glaA 5'UTR and the three synthetic
      versions (sUTR1, sUTR2, and sUTR3) as well, and placed under the control of the
      glucoamylase gene promoter. Afterwards, a total of 20 fungal transformations were
      done using A. niger N593 as a recipient strain and 50 transformants per
      transformation were isolated and analyzed. The result of the incorporation of the
      synthetic 5'UTRs on the overall productivity of the transformants was assessed,
      on one hand by monitoring the laccase activity of all the isolated transformants,
      and on the other hand by quantifying and comparing the activity of those
      secreting the highest level of each MCO. For this purpose, a high-throughput
      method for the screening and selection of the best producers was developed. Once
      the best transformants producing the highest yield of McoA, McoB, McoC, McoD, and
      McoJ laccases were selected, their production level was quantified in
      supernatants of liquid cultures. The results obtained in this work indicate that
      modifications in the native glaA 5'UTR can lead to improvements in protein
      yields.

PMID- 22949266
TI  - CD26: a negative selection marker for human Treg cells.
AB  - A major obstacle hampering the therapeutic application of regulatory T (Treg)
      cells is the lack of suitable extracellular markers, which complicates their
      identification/isolation. Treg cells are normally isolated via CD25 (IL-2Ralpha)
      targeting, but this protein is also expressed by activated CD4(+) effector T
      (Teff) lymphocytes. Other extracellular (positive or negative) Treg selection
      markers (e.g., HLA-DR, CD127) are also nonspecific. CD26 is an extracellular
      peptidase whose high expression has been traditionally used as an indicator of
      immune activation and effector functions in T cells. Now, we provide flow
      cytometry data showing high levels of CD26 within CD4(+)CD25(-) or CD4(+)FoxP3(
      /low) effector T (Teff) lymphocytes, but negative or low levels (CD26(-/low)) in
      Treg cells selected according to the CD4(+)CD25(high) or the CD4(+)FoxP3(high)
      phenotype. Unlike the negative marker CD127 (IL-7Ralpha), which is down modulated
      in CD4(+) Teff lymphocytes after TCR triggering, most of these cells upregulate
      CD26 and take a CD4(+)CD25(+/high) CD26(+) phenotype upon activation. In
      contrast, there is only a slight upregulation within Treg cells (CD4(+)CD25(high)
      CD26(-/low)). Thus, differences in CD26 levels between Treg and Teff subsets are
      stable, and assessment of this marker, in combination with others like CD25,
      FoxP3, or CD127, may be useful during the quantitative evaluation or the
      isolation of Treg cells in samples containing activated Teff lymphocytes (e.g.,
      from patients with autoimmune/inflammatory diseases).

PMID- 22949267
TI  - Preserved circannual rhythm of vitamin D in kidney transplant patients.
AB  - BACKGROUND: A high prevalence of vitamin D insufficiency has been found in the
      general population, in patients with chronic kidney disease and in kidney
      transplant patients. During winter there is a higher prevalence of vitamin D
      insufficiency due to the lack of solar ultraviolet B (UVB) exposure. Kidney
      transplant patients are advised to avoid sun exposure because of their high risk
      of skin cancer. This is considered to be one of the main reasons for the very
      high prevalence of vitamin D insufficiency in these patients. Whether circannual
      rhythm of vitamin D is totally reversed in kidney transplant patients is not
      known. METHODS: In this single centre prospective observational study, 50 kidney
      transplant patients visiting our outpatient clinic in January and February 2011
      were included. Serum concentration of 25-hydroxvitamin D (25[OH]D), 1-25
      hydroxvitamin D (1-25[OH]D) and intact parathormone (iPTH) were measured at study
      entry and 6 months later in summer. RESULTS: A total of 90% (45/50) of the study
      population had vitamin D deficiency 25(OH)D (<50 nmol/l) during winter. There was
      a rise of 25(OH)D in 94% (47/50) of patients from winter to summer (p <0.0001)
      leading to a decline of 25(OH)D deficiency from 90 to 60%, to a rise of 25(OH)D
      insufficiency from 6 to 26% and normal 25(OH)D from 4 to 14%, respectively (p =
      0.0024). CONCLUSIONS: Vitamin D insufficiency during winter is very common in
      kidney transplant patients at our centre. Despite avoidance of exposure to UVB
      there is a preserved circannual rhythm of vitamin D in kidney transplant
      patients.

PMID- 22949268
TI  - Regulation of intracellular pH in cancer cell lines under normoxia and hypoxia.
AB  - Acid-extrusion by active transport is important in metabolically active cancer
      cells, where it removes excess intracellular acid and sets the intracellular
      resting pH. Hypoxia is a major trigger of adaptive responses in cancer, but its
      effect on acid-extrusion remains unclear. We studied pH-regulation under normoxia
      and hypoxia in eight cancer cell-lines (HCT116, RT112, MDA-MB-468, MCF10A, HT29,
      HT1080, MiaPaca2, HeLa) using the pH-sensitive fluorophore, cSNARF-1. Hypoxia
      responses were triggered by pre-incubation in low O(2) or with the 2-oxoglutarate
      dependent dioxygenase inhibitor dimethyloxalylglycine (DMOG). By selective
      pharmacological inhibition or transport-substrate removal, acid-extrusion flux
      was dissected into components due to Na(+)/H(+) exchange (NHE) and Na(+)
      dependent HCO(3)(-) transport. In half of the cell-lines (HCT116, RT112, MDA-MB
      468, MCF10A), acid-extrusion on NHE was the dominant flux during an acid load,
      and in all of these, bar one (MDA-MB-468), NHE-flux was reduced following hypoxic
      incubation. Further studies in HCT116 cells showed that <4-h hypoxic incubation
      reduced NHE-flux reversibly with a time-constant of 1-2 h. This was not
      associated with a change in expression of NHE1, the principal NHE isoform.
      Following 48-h hypoxia, inhibition of NHE-flux persisted but became only slowly
      reversible and associated with reduced expression of the glycosylated form of
      NHE1. Acid-extrusion by Na(+)-dependent HCO(3)(-) transport was hypoxia
      insensitive and comparable in all cell lines. This constitutive and stable
      element of pH-regulation was found to be important for setting and stabilizing
      resting pH at a mildly alkaline level (conducive for growth), irrespective of
      oxygenation status. In contrast, the more variable flux on NHE underlies cell
      specific differences in their dynamic response to larger acid loads.

PMID- 22949269
TI  - Association of maternal diabetes and child asthma.
AB  - BACKGROUND: Perinatal programming is an emerging theory for the fetal origins of
      chronic disease. Maternal asthma and environmental tobacco smoke (ETS) are two of
      the best-known triggers for the perinatal programming of asthma, while the
      potential role of maternal diabetes has not been widely studied. OBJECTIVE: To
      determine if maternal diabetes is associated with child asthma, and if so,
      whether it modifies the effects of ETS exposure and maternal asthma. METHODS: We
      studied 3,574 Canadian children, aged 7-8 years, enrolled in a population-based
      birth cohort. Standardized questionnaires were completed by the children's
      parents, and data were analyzed by multivariable logistic regression. RESULTS:
      Asthma was reported in 442 children (12.4%). Compared to those without asthma,
      asthmatic children were more likely to have mothers (P = 0.003), but not fathers
      (P = 0.89), with diabetes. Among children without maternal history of diabetes,
      the likelihood of child asthma was 1.4-fold higher in those exposed to ETS
      (adjusted odds ratio, 1.40; 95% confidence interval, 1.13-1.73), and 3.6-fold
      higher in those with maternal asthma (3.59; 2.71-4.76). Among children born to
      diabetic mothers, these risks were amplified to 5.7-fold (5.68; 1.18-27.37) and
      11.3-fold (11.30; 2.26-56.38), respectively. In the absence of maternal asthma or
      ETS, maternal diabetes was not associated with child asthma (0.65, 0.16-2.56).
      CONCLUSION: Our findings suggest that maternal diabetes may contribute to the
      perinatal programming of child asthma by amplifying the detrimental effects of
      ETS exposure and maternal asthma.

PMID- 22949271
TI  - Proteomic profiling of osteosarcoma cells identifies ALDOA and SULT1A3 as
      negative survival markers of human osteosarcoma.
AB  - Osteosarcoma (OSA) is the most common primary malignancy of bone. Molecular
      mechanism underlying OSA remains to be fully elucidated. It is critical to
      identify reliable diagnostic and prognostic markers for OSA at the molecular
      levels. This study is designed to investigate possible molecular mechanisms
      behind OSA development and to identify novel prognostic markers related to OSA
      survival. We conduct a comprehensive proteomic profiling analysis of human OSA
      cell lines with differential metastatic potential. Through comprehensive
      combinatorial analyses of the proteomic data and the previously obtained cDNA
      microarray results, we identify 37 candidate proteins which are differentially
      expressed in OSA sublines. Among them, ALDOA and SULT1A3 are selected for further
      investigation. The expressions of protein are confirmed by Western blotting
      analysis. We further analyze the expression levels of ALDOA and SULT1A3 from 40
      clinical cases of OSA. The results demonstrate that the expression of ALDOA
      and/or SULT1A3 is significantly higher in patients with worse survival time than
      patients with better survival time. Five-year survival analysis shows there is a
      statistically significant difference between two patient populations. The data
      strongly suggest that ALDOA and/or SULT1A3 expression level in biopsy samples may
      predict the clinical outcomes of OSA patients. Furthermore, the biological
      functions of ALDOA and SULT1A3 may be implicated in OSA development and/or
      progression.

PMID- 22949272
TI  - Transdiagnostic treatment for anxiety and depression.

PMID- 22949270
TI  - Selective improvement in Seattle Heart Failure Model risk stratification using
      iodine-123 meta-iodobenzylguanidine imaging.
AB  - BACKGROUND: The Seattle Heart Failure Model (SHFM) is a multivariable model that
      uses demographic and clinical markers to predict survival in patients with heart
      failure. Inappropriate activation of the sympathetic nervous system, which
      contributes to the progression of heart failure and increased mortality, can be
      assessed using iodine-123 meta-iodobenzylguanidine (MIBG) cardiac imaging. This
      study investigated the incremental value of MIBG cardiac imaging when added to
      the SHFM for prediction of all-cause mortality. METHODS: Survival data from 961
      NYHA II-III subjects in the ADMIRE-HFX trial were included in this analysis. The
      predictive value of the SHFM alone and in combination with MIBG heart-to
      mediastinum ratio (H/M) was compared for all-cause mortality (101 deaths during a
      median follow-up of 2 years). RESULTS: The addition of H/M to the SHFM in a Cox
      model significantly improved risk prediction (P < .0001), with a greater utility
      in higher risk SHFM patients. The observed 2-year mortality in the highest-risk
      SHFM subjects (rounded SHFM score of 1) was 24%, but varied from 46% with H/M
      <1.2 to 0% with H/M >1.8. Net reclassification improvement was 22.7% (P < .001),
      with 14.9% of subjects who died reclassified into a higher risk category than
      suggested by SHFM score alone (P = .01) and 7.9% of subjects who survived
      reclassified into a lower risk category (P < .0001). The 2-year integrated
      discrimination improvement (+4.14%, P < .0001) and the 1-year area under the
      receiver-operator characteristic curve (+0.04, P = .026) both showed significant
      improvement for the combined model with H/M compared to the SHFM alone.
      CONCLUSION: The addition of MIBG imaging to the SHFM improves risk
      stratification, especially in higher risk patients. MIBG may have clinical
      utility in higher risk patients who are being considered for devices such as ICD,
      CRT-D, LVAD, and cardiac transplantation.

PMID- 22949273
TI  - Clinical inquiry in stroke: using different perspectives to guide future
      research.

PMID- 22949274
TI  - Stroke and heart disease prevention education via telenovela: a focus group's
      evaluation.
AB  - PURPOSE: To evaluate a telenovela, "La Familia Nutritiva y Balanceada," for
      cultural context and its efficacy as an educational tool to promote positive
      health behaviors in Latino families. METHOD: Ethnography was employed to
      interpret cultural health behaviors of 12 Latinas through a focus group after
      viewing the telenovela, a culturally accepted form of entertainment education.
      RESULTS: Analysis of the transcribed interview revealed three recurrent themes:
      Not all fat is bad; add fruits and vegetables daily to diet; and children need to
      be involved. The group purported that the inclusion of children in the marketing
      and preparation of the food would translate into better food habits. DISCUSSION:
      Participants demonstrated basic knowledge between food and health, and
      acknowledged that they gained an appreciation for good fat in the diet. The group
      related the telenovela would be a good tool for clinics, health fairs, and
      schools. CONCLUSION: Latinos are at high risk for cardiovascular disease and
      stroke. Health education messages need to incorporate cultural norms into an
      intervention that supports a behavior change, such as improved nutrition. Studies
      support that Latinos connect to media, such as telenovela and interpersonal
      communication, which make these appropriate choices for health education tools.

PMID- 22949275
TI  - Bladder management in female stroke survivors: translating research into
      practice.
AB  - AIMS: Impaired bladder management is common after stroke. By implementing
      evidence-based interventions, comprehensive inpatient rehabilitation can assist
      the stroke survivor in improving bladder management skills. The study goal was to
      determine if these interventions could improve bladder function of these stroke
      survivors. METHODS: This research utilization project was implemented in a free
      standing inpatient rehabilitation facility, on 35 female stroke survivors. Thirty
      five patients discharged from the same facility immediately before implementation
      of these interventions were used as the control group. RESULTS: Functional
      independence measure (FIM) bladder score was used to determine bladder function
      at admission and discharge, and to calculate FIM change. ANOVA results indicated
      that implementation of these interventions did significantly increase bladder FIM
      scores. CONCLUSIONS: Consistent implementation of evidence-based interventions by
      an interdisciplinary rehabilitation team can influence bladder management skills
      in poststroke patients.

PMID- 22949277
TI  - Examining the cost per caregiver of an intervention designed to improve the
      quality of life of spousal caregivers of stroke survivors.
AB  - BACKGROUND AND PURPOSE: There is a growing consensus among healthcare researchers
      that, within the field of family caregiving, cost-effectiveness research is
      needed to determine which programs have the greatest benefit for family members.
      This study examines the cost per caregiver of an intervention designed to improve
      the quality of life of spousal caregivers of stroke survivors. METHOD: Cost data
      from the CAReS study were analyzed to determine the cost of the intervention per
      caregiver. RESULTS: The cost of the intervention per caregiver was $2,500 at the
      2009 median wage estimate. It was $1,700 at the 2009 10 percentile wage estimate
      and $3,500 at the 2009 90 percentile wage estimate. CONCLUSIONS: This study
      provides a prototype cost analysis from which researchers can build. In future
      analyses, costs should be tracked at a participant level so uncertainty can be
      calculated using the bias-corrected percentile bootstrapping method and plotted
      to calculate cost-effectiveness acceptability curves, enabling cost-effectiveness
      comparisons between interventions.

PMID- 22949276
TI  - A problem-solving early intervention for stroke caregivers: one year follow-up.
AB  - PURPOSE: The study purposes were to assess the efficacy of a caregiver problem
      solving intervention (CPSI) on stroke caregiver physical and psychosocial
      adaptation compared with a wait-list control (WLC) treatment, and to assess the
      mediation effects of coping on outcomes. METHODS: A stress and coping model
      guided the study design. Outcomes were depression, anxiety, preparedness, life
      changes, and family functioning. CPSI started during acute rehabilitation and
      continued 3 months postdischarge. Data were collected at baseline (T1),
      postintervention (T2), and 6 (T3) and 12 months postdischarge (T4). RESULTS: Of
      255 caregivers, 75% were depressed at baseline. Repeated measures ANOVA of study
      completers (n = 121) indicated improved T2 depression, life change, and health
      (ps < .04) favoring the CPSI group. Improvements faded by 6 months. Although no
      group differences in outcomes were found in the intention-to-treat analysis,
      growth curve modeling indicated a difference in depression rate of change,
      favoring the CPSI (p = .04). Perceived health, threat appraisal and rational
      problem-solving were significant mediators (ps < .05). CONCLUSIONS: Findings
      provide direction for future interventions to promote and sustain healthy
      caregiver adaptation.

PMID- 22949278
TI  - Adequate oral fluid intake in hospitalized stroke patients: does viscosity
      matter?
AB  - PURPOSE: Sufficient intake of oral fluids to meet hydration needs is a critical
      recovery issue for patients hospitalized post stroke. Concerns for adequate oral
      fluid intake are generally focused on dysphagic patients restricted to thickened
      liquids; however, fluid intake patterns in stroke patients receiving thin liquids
      are unknown. METHOD: This study examines the oral fluid intake patterns of three
      groups over 72 hours: community dwelling individuals, patients hospitalized post
      stroke receiving thin liquids and patients hospitalized post stroke receiving
      thickened liquids. RESULTS: Mean oral fluid intake differed significantly between
      the two hospitalized groups (p = .04), with individuals receiving thickened
      liquids consuming less. Less than 1% of patients hospitalized post stroke met a
      minimum standard of 1500 mL/day, regardless of liquid viscosity. Conversely,
      community dwelling participants consumed significantly more fluids on average
      than their hospitalized counterparts. CONCLUSION: Compliance with beverage
      preference, frequency of beverage offering, and inaccurate preparation of
      thickened beverages were identified as factors potentially influencing fluid
      intake.

PMID- 22949281
TI  - Vitamin D intake cannot represent the extent of vitamin D deficiency or
      insufficiency: comment on the article by Hiraki et al.

PMID- 22949279
TI  - Caregivers' incongruence: emotional strain in caring for persons with stroke.
AB  - PURPOSE: Guided by Friedemann's framework, the purpose of this study was to
      examine the dimensions of new family caregivers' emotional strain in caring for
      persons with stroke. METHOD: Seventy-three caregivers who were new to that role
      participated in an interview every 2 weeks for a year as part of a NIH project.
      Of these caregivers, 36 participants were randomly assigned and had access to a
      Web-based intervention and its e-mail discussion. In this secondary data
      analysis, 2,148 e-mail discussion messages plus 2,455 narrative interview entries
      were used to examine dimensions of caregivers' emotional strain. Rigorous content
      analysis was applied to these data. RESULTS: The majority of these caregivers
      were white women with an average of 55 years who cared for spouses. Three themes
      emerged from these data: (1) being worried, (2) running on empty, and (3) losing
      self. DISCUSSION: Caregivers worried about themselves and their care recipient,
      sharing feelings of being just "plain tired." The caregivers felt that their
      lives were lost to giving care. They described in detail the emotional strain
      that they felt, as they took on new roles in caring for the person with stroke.
      CONCLUSION: This study informs nurses about new family caregivers' emotional
      strain, or incongruence in Friedemann's terms, from their viewpoint and provides
      direction for supportive education interactions.

PMID- 22949282
TI  - Paramagnetic particles coupled with an automated flow injection analysis as a
      tool for influenza viral protein detection.
AB  - Currently, the influenza virus infects millions of individuals every year. Since
      the influenza virus represents one of the greatest threats, it is necessary to
      develop a diagnostic technique that can quickly, inexpensively, and accurately
      detect the virus to effectively treat and control seasonal and pandemic strains.
      This study presents an alternative to current detection methods. The flow
      injection analysis-based biosensor, which can rapidly and economically analyze a
      wide panel of influenza virus strains by using paramagnetic particles modified
      with glycan, can selectively bind to specific viral A/H5N1/Vietnam/1203/2004
      protein-labeled quantum dots. Optimized detection of cadmium sulfide quantum dots
      (CdS QDs)-protein complexes connected to paramagnetic microbeads was performed
      using differential pulse voltammetry on the surface of a hanging mercury drop
      electrode (HMDE) and/or glassy carbon electrode (GCE). Detection limit (3 S/N)
      estimations based on cadmium(II) ions quantification were 0.1 MUg/mL or 10 MUg/mL
      viral protein at HMDE or GCE, respectively. Viral protein detection was directly
      determined using differential pulse voltammetry Brdicka reaction. The limit
      detection (3 S/N) of viral protein was estimated as 0.1 MUg/mL. Streptavidin
      modified paramagnetic particles were mixed with biotinylated selective glycan to
      modify their surfaces. Under optimized conditions (250 MUg/mL of glycan, 30-min
      long interaction with viral protein, 25 degrees C and 400 rpm), the viral protein
      labeled with quantum dots was selectively isolated and its cadmium(II) content
      was determined. Cadmium was present in detectable amounts of 10 ng per mg of
      protein. Using this method, submicrogram concentrations of viral proteins can be
      identified.

PMID- 22949283
TI  - Handedness in infants' tool use.
AB  - In this study, we investigated whether hand preference influences infants' choice
      of what hand to use in grasping a new tool presented at the midline, and whether
      this will change in the course of learning the functionality of a tool. The tool
      was a rake within reach placed beside an out-of-reach toy presented either to its
      right or to its left. Forty-eight infants from 16 to 22 months of age were
      tested. The results show that use of the right-preferred hand to grasp the rake
      is strong as of 16 months of age and does not change significantly with age in
      the condition where using the right hand leads to a better outcome than using the
      left hand. In the condition where using the left-non-preferred hand makes toy
      retrieval easier, infants increasingly use the left hand with age. Thus, when
      grasping the tool, younger infants are more influenced by their hand preference
      than older infants, who are better at anticipating the most successful
      strategies.

PMID- 22949284
TI  - [Lifetime prevalence and correlates of schizophrenia and disorders with psychotic
      symptoms in the general population of Izmir, Turkey].
AB  - OBJECTIVE: To estimate the lifetime prevalence of 12 DSM-IV disorders with
      psychotic symptoms in a general population survey. METHOD: Addresses were
      contacted in a multistage clustered area probability sampling frame of
      administrative neighbourhoods and households, covering 9 districts and 302
      neighbourhoods in the Izmir metropolitan area between November 2007 and October
      2008. One household member aged between 15 and 64 years and available to complete
      the interview was randomly selected using a within-household sampling method. The
      primary screening instrument was the Composite International Diagnostic Interview
      2.1. A systematic screening procedure was implemented to detect probable cases
      with any psychotic disorder. Those selected by the screens were re-interviewed
      with the Structured Clinical Interview for DSM-IV. Diagnoses of individuals who
      were not available for re-interview were made by combining screening information
      with case register diagnoses and/or the telephone interviews with relatives or
      spouse. RESULTS: A total of 4011 individuals were screened for disorders with
      psychotic symptoms. After screening, 499 respondents were selected as a probable
      case. 277 of screen positive respondents were available for clinical reappraisal.
      Initial screening interviews and additional material were used for best estimate
      diagnoses of the remaining 172 respondents. Total lifetime prevalence of 12 DSM
      IV disorders with psychotic symptoms was 2.62%. Lifetime prevalence of each
      disorder separately were as follows: 0.74% for schizophrenia, 0.20% for
      schizoaffective disorder, 0.05% for schizophreniform disorder, 0.10% for
      delusional disorder, 0.12% for brief psychotic disorder, 0.55% for major
      depressive disorder with psychotic features, 0.37% for bipolar I disorder, 0.20%
      for substance induced psychotic disorder, and 0.07% for psychotic disorders due
      to a general medical condition. CONCLUSION: Total lifetime prevalence of
      disorders with psychotic symptoms is higher than any previously reported
      estimates in Turkey; with a prevalence of approximately 2.5%, these disorders can
      be considered a major public health concern.

PMID- 22949285
TI  - [Mapping genes related to early onset major depressive disorder in Dagestan
      genetic isolates].
AB  - AIM: The purpose of this study was to determine the molecular epidemiology of
      early onset major depressive disorder (MDD) in genetic isolates of the Caucasus
      Dagestan indigenous ethnic populations using molecular and statistical population
      genetic approaches. METHODS: Two multigenerational pedigrees from two diverse
      remote highland isolates with aggregation of early onset MDD were ascertained
      within our long-term research program titled 'Dagestan Genetic Heritage, DGH'.
      The first isolate included 48 cases of MDD (19 living) with 11 suicides
      committed, and the second included 60 MDD cases (30 living) with 12 suicides
      committed. The phenotypes of the affected family members were determined using a
      database containing diagnoses from a regional psychiatric hospital and through
      our own clinical examinations, which were based on a Russian translation of DIGS
      software based on the DSM-IV criteria . A 10 cM genomic scan (Weber/CHLC 9.0
      STRs) of the 64 affected and non-affected members of the pedigrees was performed
      and the data was used for multipoint parametric linkage analyses. Following this
      scan, selected cases were analyzed by Affymetrix 6.0 SNP arrays in order to
      refine the contribution of copy number variations (CNVs) to the genetic basis of
      MDD. RESULTS: We found a total of 18 genomic regions with nominal (LOD>1.3)
      linkage to MDD across the two isolates. Three genomic regions had genome-wide
      significant (LOD>3) linkages and were found at 2p13.2-p11.2, 14q31.12-q32.13 and
      22q12.3. We also confirmed previous findings for MDD at 4q25, 11p15, 12q23-24,
      13q31-32, 18q21-22 and 22q11-13. Six linkage regions were observed in both
      genetic isolates, while 12 other linkages demonstrated population-specific
      heterogeneity. We detected CNV rearrangements within 12 of the 18 linkage
      regions. Affected subjects had the highest rate of genomic instability within the
      linkage regions at 2p13.2-p11.2, 4q25-q28.2, 7p14.1, 8p23, 14q31.12-q32.13,
      18q22.1 and 20p13. CONCLUSION: The results obtained in this study suggest that
      mapping genes of complex diseases, including MDD, across genetically homogeneous
      isolates can help detect linkage signals and expedite the search for
      susceptibility genes when combined with methods that detect structural genomic
      variation in linkage regions.

PMID- 22949286
TI  - [The relationship between right hemi-space visuospatial attention disturbance and
      anger in antisocial individuals].
AB  - OBJECTIVE: Evidence suggests that individuals with antisocial personality
      disorder (APD) exhibit a less asymmetric pattern than healthy controls during
      auditory and visuospatial attention tasks characterized by a right hemispheric
      advantage; however, the association between attention asymmetry and
      symptomatology is not clear. The present study aimed to examine the relationship
      between visuospatial attention in the right and left hemi-spaces, and various
      dimensions of anger in individuals with APD. MATERIALS AND METHODS: We compared
      visuospatial attention performance in the right and left hemi-spaces during a
      computerized Line Bisection Test (LBT) in individuals with APD (n = 52) and
      healthy controls (n = 34). We also administered the Multi-Dimensional Anger Scale
      (MDAS) to both groups. RESULTS: Subjects in the APD group made larger bisection
      errors than healthy controls only during the right hemi-space condition and had
      higher scores than those in the control group on all MDAS dimensions of anger.
      The severity of anger symptoms and thoughts were predicted by right hemi-space
      visuospatial attention disturbance in the APD group, whereas no such association
      was observed in the control group. CONCLUSION: The present findings either
      suggest a left hemisphere neuropathology or a disturbance in inter-hemispheric
      transmission in the APD group. Right hemi-space-specific visual attention
      disturbance may mediate the relationship between neuropathology, and somatic and
      trait dimensions of anger in APD.

PMID- 22949287
TI  - [How is quality of life affected in women in the presence of anxiety and
      depression symptoms?].
AB  - OBJECTIVE: To assess how quality of life is affected among reproductive age women
      from the presence of anxiety and depression symptoms and the risk factors related
      to both. METHOD: A cross sectional analytic study was performed in person with
      461 women. General Health Questionnarie-12 and WHOQOL-BREF were used. RESULTS:
      35.5% of the women displayed symptoms of anxiety and depression and those who had
      experienced domestic violence had a 2.61-fold increase in symptom frequency and
      those with an income below 500 TL had a 2.49-fold more frequent occurrence of
      symptoms compared to others. General health quality mean score was 3.33 +/-
      0.804, the mean overall quality of life was 3.62 +/- 0.791; Physical Health
      Domain: 15.95 +/- 2.422; Psychological Health Domain: 14.70 +/- 2.337; Social
      Relations Domain 14.64 +/- 3,027; Environmental Domain 14:27 +/- 2.20; National
      Domain 14:29 +/- 2.144l. The total score of GHQ-12 and the first two questions of
      WHOQOL-BREF had a negative, moderate and highly significant correlation, whereas
      the Psychological HD score had a a negative,, strong and significant correlation
      All other domains and the total score of GHQ-12 had negative, moderate and 
      significant correlations. CONCLUSION: Screening with GHQ-12 as well as offering
      the possibility of early diagnosis and treatment, is also important to prevent
      impairment in all areas of quality of life among women. Early diagnosis and
      treatment of psychological problems of women with risk factors such as exposure
      to domestic violence and low socio-economic status are the intervention areas
      with priority.

PMID- 22949288
TI  - [The mortality rate among patients with delirium 6 months after diagnosis by a
      consultation-liaison psychiatric team].
AB  - AIM: Data from Western countries suggest that delirium is associated with a high
      rate of mortality; however, the mortality rate in patients with delirium in India
      has not been studied. The aim of this study is to determine the mortality rate
      among a group of hospitalized patients with delirium 6 months after being
      diagnosed with delirium. METHODOLOGY: The study included 97 patients with
      delirium that were evaluated by the consultation-liaison psychiatric team.
      Informed consent was provided by the patients' caregivers. The patients were
      rated according to the Delirium Rating Scale-Revised 98 (DRS-R-98) and Delirium
      Motor Subtype Scale, and the etiology of delirium was recorded using a structured
      format. RESULTS: Mean age of the patients was 47.14 +/- 18.10 years and mean
      duration of formal education was 8.35 +/- 5.63 years. Most of the patients were
      male (n = 69, 71.13%) and had hospital-emergent delirium (n = 68, 70.10%). Mean
      duration of delirium was 4.15 +/- 5.71 d at the time of assessment and mean DRS-R
      98 score was 30.71 +/- 4.82. Among the 97 patients, 12 (12.1%) died during their
      hospital stay- a higher mortality rate than that observed in other patients
      referred for consultation-liaison psychiatric services that were diagnosed with
      psychiatric disorders other than delirium (4.43%) or not diagnosed with a
      psychiatric disorder (no deaths) during the same time period. The mortality rate
      in patients with delirium was also significantly higher than that seen among all
      other hospital admissions during the study period (6.79%; 2119 deaths among
      31,190 admissions; chi-square value: 4.73; P = 0.02). Mortality rate in patient's
      with delirium at 6 month follow-up was 27.83%. CONCLUSIONS: Delirium in
      hospitalized patients is associated with a high mortality rate.

PMID- 22949289
TI  - [Reliability and validity study of the Turkish version of functioning assessment
      short test in bipolar disorder].
AB  - OBJECTIVE: There is a need for instruments to assess the Functioning Assessment
      Short Test practically. In this study the goal was to to perform a reliability
      and validity analyses of the Functioning Assessment Short Test (FAST) in bipolar
      disorder. METHOD: The study was harbored 70 patients with bipolar disorder and
      134 healthy control subjects. Thirteen of the patients were in the manic episode,
      16 were in the depressive episode, and 41 patients were in remission. First, FAST
      was translated into Turkish and then it was back-translated into English. The
      translation was finally approved by the author of the original development study.
      In the concurrent validity, Bipolar Disorder Functioning Questionnaire (BBi) was
      used. RESULTS: In the reliability analyses, Cronbach alpha coefficient of
      internal consistency was calculated to be 0.960, and test-retest reliability
      coefficient was found to be 0.945. In the validity analyses, in the exploratory
      factor analysis five factors were obtained and the factor represented social
      functioning, occupational functioning, autonomy, cognitive functioning and
      financial issues. In the confirmatory factor analysis, comparative fit index was
      0.912 and RMSEA value was 0.085. In the concurrent validity analyses, the domains
      of FAST were correlated poorly to moderately with the subscales of BBi. FAST
      discriminated bipolar patients with symptomatic episodes and remitted patients,
      healthy controls. The area under the ROC curve was found to be 0.824. CONCLUSION:
      These results point out that the Turkish version of Functioning Assessment Short
      Test can used reliably and validly in bipolar patients.

PMID- 22949290
TI  - [Unipolar mania: a distinct entity or characteristic of manic preponderance?].
AB  - OBJECTIVE: It has been reported that fewer patients with unipolar mania respond
      to lithium prophylaxis as do those with classical bipolar disorder. This study
      aimed to determine if the difference to response to lithium is related to
      unipolar mania or to a high preponderance of mania during the course of
      bipolarity. MATERIALS AND METHODS: The study included bipolar-I patients
      (according to DSM-IV criteria) that had a >= 2-year history of either lithium or
      valproate prophylaxis as monotherapy. The response rate in the patients with
      unipolar mania and classical bipolar disorder were compared. Then, the response
      rate to lithium in all the patients with a manic episode rate <50% and >50%, and
      <80% and >80% during their course were compared. Finally, the above comparisons
      were repeated, excluding the patients with unipolar mania. RESULTS: The study
      included 121 bipolar-I patients (34 unipolar mania and 87 classical bipolar
      disorder). The response rate to lithium prophylaxis was significantly lower in
      the unipolar mania group than that in the bipolar group, whereas, the response
      rate to valproate prophylaxis was similar in both groups. Additionally,
      significantly fewer patients with a manic episode rate >80% during their course
      responded to lithium, followed by those with a manic episode rate >50%; however,
      these differences disappeared when the unipolar mania group was excluded from the
      comparison. CONCLUSION: Fewer patients with unipolar mania responded to lithium
      prophylaxis than those with classical bipolar disorder, which appeared to be
      related to unipolar mania, rather than to a high manic predominance during the
      disease course. On the other hand, response to valproate prophylaxis was similar
      in the unipolar mania and classical bipolar disorder groups.

PMID- 22949291
TI  - [Cognitive-behavioral group treatment for schizophrenia and other psychotic
      disorders- a systematic review].
AB  - OBJECTIVE: This study aims to revise empirical studies that were used to evaluate
      the effectiveness of cognitive-behavioral group treatment programs in the
      treatment for schizophrenia and other psychotic disorders. METHOD: Articles in
      English that were published between the years of 1980 and 2011 (july) have been
      searched in the: PsycINFO, PsycARTICLES and MEDLINE databases by using "(1)
      psychosis and cognitive treatment (2) schizophrenia and cognitive treatment, (3)
      schizophrenia and cognitive therapy, (4) psychosis and cognitive therapy, (5)
      schizophrenia and cognitive intervention (6), psychosis and cognitive
      intervention, (7) hallucination and cognitive therapy, (8) hallucination and
      cognitive treatment, (9) hallucination and cognitive intervention" keywords. The
      articles that were gathered by the search have been read and the ones that were
      not therapy effectiveness studies, group therapies were eliminated. RESULTS: The
      remaining 42 studies that were in conformance with the search criteria were
      introduced in the context of method (properties of population, measures,
      randomization, results, follow-up, etc.) and therapy characteristics (number of
      sessions, frequency of sessions, number of therapists and members, etc.).
      CONCLUSION: It can be seen that the cognitive behavioral therapies plus standard
      treatment that are applied to people who have schizophrenia and other psychotic
      disorders are effective in decreasing the symptoms of the disorders (positive and
      negative symptoms etc.) and/or the problems that accompany the disorder (anxiety,
      hopelessness etc.).

PMID- 22949292
TI  - [Mania associated with Usher syndrome type II].
AB  - Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder
      characterized by sensorineural deafness, retinitis pigmentosa, and variable
      vestibular deficit; Usher syndrome type II is the most common form. Various
      neuropsychiatric disorders have been reported to occur in those with Usher
      syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent
      depressive illness, neurotic disorder, and mental retardation; however, bipolar
      disorder is not common in those with Usher syndrome.    Herein we describe a 30
      year-old male with Usher syndrome type II that developed features indicative of a
      probable manic episode. The patient had complete remission of symptoms in
      response to treatment with olanzapine 20 mg d-1. In persons with dual sensory
      impairment there are inherent problems with assessment and diagnosis is difficult
      due to their limited communication abilities. The diagnosis of Usher syndrome
      depends heavily on behavioral observation and disturbances in vegetative
      functions.

PMID- 22949294
TI  - Integrated electrokinetic sample fractionation and solid-phase extraction in
      microfluidic devices.
AB  - A microfluidic device that performs "in space" sample fractionation, collection,
      and preconcentration for proteomics is described. Effluents from a 2.75 mm long
      fractionation channel, focused via sheath flow, were sequentially delivered into
      an array of 36-collection channels containing monolithic polymer beds for SPE.
      Optimum conditions for the device design, and simultaneous photolytic fabrication
      of 36 monolithic columns in the 36 channels, as well as for their proper
      performance in electrokinetic sample fractionation and collection are described.
      A hydrophobic butyl methacrylate-based monolithic porous polymer was
      copolymerized with an ionizable monomer, acryloamido-methyl-propane sulfonate, to
      form a polymer monolith for SPE that also sustains cathodic electroosmotic flow.
      The SPE bed was made deep enough to greatly reduce the linear flow rate within
      the bed, in order to compensate for the lower electroosmotic mobility of the
      cationically charged SPE bed relative to the glass walled device. Under these
      conditions, electrokinetic fractionation of a protein sample resulted in tightly
      focused sample zones delivered into each of the 36-channel polymer beds with no
      observed crosscontamination. Monolithic columns showed reproducible performance
      with preconcentration factor of 30 for 2 min loading time. The ability to
      fractionate, collect, and preconcentrate samples on a microfluidic platform will
      be especially useful for automated or continuous operation of these devices in
      proteomics research.

PMID- 22949295
TI  - Abnormality of maternal-to-embryonic transition contributes to MEHP-induced mouse
      2-cell block.
AB  - Mono (2-ethylhexyl) phthalate (MEHP), an environmental contaminant, is known to
      cause many serious diseases, especially in reproductive system. However, little
      is known about the effect of MEHP on preimplantation embryo development. In this
      study, we found that the development of mouse 2-cell embryo was blocked by 10(-3)
      M MEHP. A significant increase in the level of reactive oxygen species (ROS) was
      observed in arrested 2-cell embryo following 10(-3)  M MEHP treatment for 24 h.
      However, antioxidants, catalase (CAT), and superoxide dismutase (SOD), reduced
      intracellular ROS and protected MEHP-exposed embryos from death but failed to
      return the arrested embryos. Further experiments demonstrated that the level of
      apoptosis was not altered in live arrested 2-cell embryo and increased in dead
      arrested 2-cell embryo after MEHP treatment, which implied that ROS and apoptosis
      were not related with 2-cell block. During analysis of the indicators of
      embryonic genome activation (EGA) initiation (Hsc70, MuERV-L, Hsp70.1, eIF-1A,
      and Zscan4) and maternal-effect genes (OCT4 and SOX2), we found that MEHP
      treatment could significantly decline Hsc70, MuERV-L mRNA level and SOX2 protein
      level, and markedly enhance Hsp70.1, eIF-1A, Zscan4 mRNA level, and OCT4 protein
      level at 2-cell to 4-cell stage. Supplementation of CAT and SOD did not reverse
      the expression tendency of EGA related genes. Collectively, this study
      demonstrates for the first time that MEHP-induced 2-cell block is mediated by the
      failure of EGA onset and maternal-effect genes, not oxidative stress and
      apoptosis.

PMID- 22949296
TI  - The effectiveness of internet cognitive behavioural therapy for generalized
      anxiety disorder in clinical practice.
AB  - BACKGROUND: Clinical trials have demonstrated the efficacy of internet cognitive
      behavioral therapy (iCBT) in the treatment of generalized anxiety disorder (GAD).
      The current study aims to determine whether these efficacy findings, established
      under controlled research conditions, translate into effectiveness in practice.
      METHODS: The sample comprised 588 patients who completed at least one iCBT lesson
      for GAD through CRUfAD clinic (www.crufadclinic.org). This six-lesson course
      became available to primary care physicians to prescribe in 2009. Routine data
      collection included demographics, GAD symptomatology (GAD-7), psychological
      distress (K-10), and disability (WHODAS). RESULTS: All six lessons were completed
      by 324/588 (55.1%) patients. When compared with completers, noncompleters tended
      to be younger and based in rural locations. Prior to discontinuing the course,
      noncompleters demonstrated statistically significant reductions in psychological
      distress. For those who completed the course, effect sizes on all outcome
      measures were medium to large and over 60% of moderate-to-severe GAD cases met
      criteria for remission upon treatment completion. CONCLUSIONS: The current study
      indicates that computerized CBT for GAD is effective in generating positive,
      clinically significant outcomes among typical patients treated under the usual
      conditions in primary care. Future research should focus on reducing treatment
      discontinuation among younger people and those based in rural locations.

PMID- 22949297
TI  - Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary
      exacerbations: II. cephalosporins and penicillins.
AB  - Acute pulmonary exacerbations (APE) are well-described complications of cystic
      fibrosis (CF) and are associated with progressive morbidity and mortality.
      Despite aggressive management with two or more intravenous anti-pseudomonal
      agents, approximately 25% of exacerbations will result in a loss of lung
      function. The aim of this review is to provide an evidence-based summary of
      pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies
      utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and
      penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the
      treatment of APE and to identify areas where further study is warranted. The
      ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day
      divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8
      hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for
      piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18
      24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up
      to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF
      patients will not regain their lung function following an APE, we suggest the
      need to optimize antibiotic dosing and dosing regimens used to treat an APE in
      efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa.
      Future studies are needed to determine the clinical efficacy of higher than FDA
      approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The
      usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to
      treatment-related adverse effects. Further understanding of these adverse effects
      in CF patients is needed.

PMID- 22949298
TI  - Histogenesis of the unique morphology of proboscidean ivory.
AB  - The chequered pattern (often called Schreger pattern), which can be seen by
      unaided eye on transverse profiles of several proboscidean tusks and which can be
      emphasized by the spreading pattern of the cracks or by mineral discoloration, is
      an autapomorph feature of the clade Elephantoidea. The pattern differs among
      proboscidean taxa; therefore, it allows the coarse differentiation of elephants,
      mammoths, and some other basal groups. Such identification methods could
      facilitate efforts concerned with protection of the remaining elephant
      populations through ivory trade restrictions, since the tooth dentine from
      extinct Mammuthusprimigenius and from extant Loxodontaafricana and Elephasmaximus
      are the most common raw materials of the ivory carvings. The aim of this study
      was to show the internal structure of proboscidean ivory and to revise the
      existing theories on the aforementioned pattern of the elephantoids with
      reflections on the events which lead to the development of this microstructure.
      Thin sections and natural crack surfaces with various orientations of
      M.primigenius, Elephasantiquus, Prodeinotherium, and Deinotherium tusk fragments
      were used to produce a three-dimensional model which explains the features on all
      profiles. The "phase shift" model is introduced, which assumes a sinusoid
      undulation of the dentinal tubules in radial profiles in the case of
      elephantoids. The model was confirmed by photomicrographs, scanning electron
      microscopic images, interpretation of natural crack surfaces, and radial
      displacement analysis of the dentinal tubules. The latter proved that the
      adjacent waves are not in the same phase. Several new nondestructive
      distinguishing methods are described here on the basis of the correlation between
      some microscopic and macroscopic features related to the Schreger pattern.

PMID- 22949300
TI  - [In process citation].
AB  - INTRODUCTION : An estimated 300 to 500 million clinical cases of malaria occur
      each year worldwide, 90% in Africa, mostly among young children. In Cote
      d'Ivoire, malaria is 46.03% of disease states and 62.44% of hospital admissions.
      In children under 5 years, it is 42.67% of the reasons for consultation and
      59.68% of hospital admissions. In pregnant women, it represents 22.91% of disease
      states and 36.07% of hospital admissions. In Africa, traditional medicine is the
      first resort for the vast majority of people, because of its accessibility both
      geographically, economically and culturally. However, some modern practitioners
      show an attitude of distrust of traditional medicine and its players, calling
      them irrational. This work had set out to assess knowledge, attitudes and
      practices of traditional healers in the uncomplicated and complicated in the
      context of collaboration between traditional and modern medicine for the optimal
      management of critical cases. MATERIALS AND METHOD : The study focused on
      traditional healers practicing in the city of Abidjan. The study was conducted
      using individual interviews over a period of 30 days. The interviews were
      conducted in local languages, with the assistance, if necessary, translators. For
      data collection, we used a questionnaire containing four items: the socio
      demographic characteristics of traditional healers, their knowledge on malaria,
      diagnostic practices and traditional therapies. RESULTS : Of the 60 healers and
      included in the study, only six were women (10%), a sex-ratio of a woman to 9
      men. 66.7% of respondents traditional healers are herbalists and 25% of
      naturopaths.Only 8.3% were spiritualists. The etiology of malaria most commonly
      cited by the traditional healers were mosquito bites (16.7%), food (1.7%), solar
      (1.7%) and fatigue (1.7%) . 25% of traditional healers are associated with
      mosquitoes, sun and fatigue. Symptomatology most cited were fever (100%), dark
      urine (86%), the yellow or pale conjunctiva (80%), vomiting (71.7%), nausea
      (58.3%) and abdominal pain (48.3%). Traditional healers recognized three types of
      malaria: the white shape, form yellow / red and the black form. Traditional
      healers malarious patients surveyed were receiving both first (58.3%) than second
      line (41.7%). 78.3% of them practiced an interview and physical examination of
      theirpatients before the diagnosis. In 13.3% of cases they were divinatory
      consultation. Medications used to treat malaria were herbal in 95% of cases. The
      main sign of healing was the lack of fever (58.3%). 90%of traditional healers
      interviewed referring cases of malaria black (severe malaria). This reference is
      made to modern health facilities (90.2%). 68.3% of respondents practiced
      traditional healers of malaria prophylaxis among pregnant women and children
      under 5 years.CONCLUSION : A description of clinical malaria by traditional
      practitioners in health is not very far from that of modern medicine.
      Nevertheless, the logics of our respondents are etiological more complex and
      linked to their cultural context. The management of cases is made from medicinal
      plants in treatment failure patients are usually referred to modern health
      facilities. The involvement of traditional healers in the detection and quick
      reference risk cases can contribute to reducing child mortality due to severe
      malaria.

PMID- 22949299
TI  - Ferritin as a novel reporter gene for photoacoustic molecular imaging.
AB  - Reporter genes may serve as endogenous contrast agents in the field of
      photoacoustic (PA) molecular imaging (PMI), enabling greater characterization of
      detailed cellular processes and disease progression. To demonstrate the
      feasibility of using ferritin as a reporter gene, human melanoma SK-24 (SK-MEL
      24) cells were co-transfected with plasmid expressing human heavy chain ferritin
      (H-FT) and plasmid expressing enhanced green fluorescent protein (pEGFP-C1) using
      lipofectamineTM 2000. Nontransfected SK-MEL-24 cells served as a negative
      control. Fluorescent imaging of GFP confirmed transfection and transgene
      expression in co-transfected cells. To detect iron accumulation due to ferritin
      overexpression in SK-MEL-24 cells, a focused high-frequency ultrasonic transducer
      (60 MHz, f/1.5), synchronized to a pulsed laser (fluence < 5 mJ/cm(2)) was used
      to scan the PA signal at a wide range NIR wavelengths (850-950 nm). PA signal
      intensity from H-FT transfected SK-MEL-24 cells was about 5-9 dB higher than
      nontransfected SK-MEL-24 cells at 850-950 nm. Immunofluorescence and RT-PCR
      analysis both indicate high levels of ferritin expression in H-FT transfected SK
      MEL24 cells, with little ferritin expression in nontransfected SK-MEL-24 cells.
      In this study, the feasibility of using ferritin as a reporter gene for PMI has
      been demonstrated in vitro. The use of ferritin as a reporter gene represents a
      novel concept for PMI using an endogenous contrast agent and may provide various
      opportunities for molecular imaging and basic science research.

PMID- 22949301
TI  - Sociodemographic risk, parenting, and effortful control: relations to salivary
      alpha-amylase and cortisol in early childhood.
AB  - Early sociodemographic risk, parenting, and temperament were examined as
      predictors of the activity of children's (N = 148; 81 boys, 67 girls)
      hypothalamic-pituitary-adrenal axis and autonomic nervous system. Demographic
      risk was assessed at 18 months (T1), intrusive/overcontrolling parenting and
      effortful control were assessed at 30 months (T2), and salivary cortisol and
      alpha-amylase were collected at 72 (T3) months of age. Demographic risk at T1
      predicted lower levels of children's effortful control and higher levels of
      mothers' intrusive/overcontrolling parenting at T2. Intrusive/overcontrolling
      parenting at T2 predicted higher levels of children's cortisol and alpha-amylase
      at T3, but effortful control did not uniquely predict children's cortisol or
      alpha-amylase levels. Findings support the open nature of stress responsive
      physiological systems to influence by features of the early caregiving
      environment and underscore the utility of including measures of these systems in
      prevention trials designed to influence child outcomes by modifying parenting
      behavior.

PMID- 22949302
TI  - Oroxylin A prevents inflammation-related tumor through down-regulation of
      inflammatory gene expression by inhibiting NF-kappaB signaling.
AB  - Increasing evidence suggests that inflammatory microenvironment plays a critical
      role at different stages of tumor development. However, the molecular mechanisms
      of the interaction between inflammation and proliferation of cancer cells remain
      poorly defined. Here we reported the inhibitory effects of oroxylin A on the
      inflammation-stimulated proliferation of tumor cells and delineated the mechanism
      of its action. The results indicated that treatment with oroxylin A inhibited NF
      kappaB p65 nuclear translocation and phosphorylation of IkappaBalpha and
      IKKalpha/beta in both human colon tumor HCT116 cells and human monocytes THP-1
      cells. In addition, in THP-1 cells, oroxylin A significantly suppressed
      lipopolysaccharide (LPS)-induced secretion of prototypical proinflammatory
      cytokine IL-6 but not IL-1beta, and it was confirmed at the transcription level.
      Moreover, oroxylin A inhibited the proliferation of HCT116 cells stimulated by
      LPS-induced THP-1 cells in co-culture microenvironment. In summary, oroxylin A
      modulated NF-kappaB signaling pathway involved in inflammation-induced cancer
      initiation and progression and therefore could be a potential cancer
      chemoprevention agent for inflammation-related cancer.

PMID- 22949303
TI  - High-sensitivity C-reactive protein, disease activity, and cardiovascular risk
      factors in systemic lupus erythematosus.
AB  - OBJECTIVE: To study the level of high-sensitivity C-reactive protein (hsCRP) and
      its relationship with disease activity, damage, and cardiovascular risk factors
      in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive
      patients who fulfilled >=4 American College of Rheumatology criteria for SLE who
      did not have a concurrent infection were recruited. Blood was assayed for hsCRP
      level, and disease activity, organ damage of SLE, and cardiovascular risk factors
      were assessed. Linear regression analyses were performed for the relationship
      between hsCRP levels, SLE activity, damage, and cardiovascular risk factors.
      RESULTS: In total, 289 patients were studied (94% women, mean +/- SD age 39.0 +/-
      13.1 years, and mean +/- SD SLE duration 7.8 +/- 6.7 years). The mean +/- SD
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4.9 +/-
      5.6 and clinically active SLE was present in 122 patients (42%). The mean +/- SD
      hsCRP level was 4.87 +/- 12.7 mg/liter, and 28 patients with active SLE (23%) had
      an undetectable hsCRP level (<0.3 mg/liter). The linear regression analyses
      revealed a significant correlation between hsCRP level and musculoskeletal
      disease (beta = 0.21), hematologic disease (beta = 0.19), active serositis (beta
      = 0.46), and clinical SLEDAI score (beta = 0.24) after adjusting for age, sex,
      body mass index, serum creatinine, and the use of various medications (P < 0.005
      for all). hsCRP levels correlated significantly with anti-double-stranded DNA
      titer (beta = 0.33, P < 0.001) but did not correlate with complement C3 (beta = 
      0.07, P = 0.26). An hsCRP level >3 mg/liter was significantly associated with
      male sex, long-term smoking, diabetes mellitus, a higher atherogenic index, and a
      history of arterial thrombosis. hsCRP levels correlated significantly with
      pulmonary and endocrine damage scores. CONCLUSION: hsCRP was detectable in 77% of
      SLE patients with clinically active disease and correlated with SLEDAI scores,
      particularly in serositis and in the musculoskeletal and hematologic systems.
      Elevated hsCRP levels in SLE were associated with certain cardiovascular risk
      factors and a history of arterial thromboembolism.

PMID- 22949304
TI  - High-dimensional gene expression profiling studies in high and low responders to
      primary smallpox vaccination.
AB  - BACKGROUND: The mechanisms underlying smallpox vaccine-induced variations in
      immune responses are not well understood, but are of considerable interest to a
      deeper understanding of poxvirus immunity and correlates of protection. METHODS:
      We assessed transcriptional messenger RNA expression changes in 197 recipients of
      primary smallpox vaccination representing the extremes of humoral and cellular
      immune responses. RESULTS: The 20 most significant differentially expressed genes
      include a tumor necrosis factor-receptor superfamily member, an interferon (IFN)
      gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones
      (P <= 1.06E(-20), q <= 2.64E(-17)). A pathway analysis identified 4 enriched
      pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being
      the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of
      IFNs, P = 8.95E(-05); and IFN-alpha/beta signaling pathway, P = 2.92E(-04)),
      integral to innate immunity, were enriched when comparing high with low antibody
      responders (false discovery rate, < 0.05). Genes related to immune function and
      transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P
      <= .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on
      immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found
      to be expressed differentially in high versus low antibody responders.
      CONCLUSION: We identified novel and known immunity-related genes and pathways
      that may account for differences in immune response to smallpox vaccination.

PMID- 22949305
TI  - HHV-8, transfusion, and mortality.

PMID- 22949306
TI  - Protein energy malnutrition decreases immunity and increases susceptibility to
      influenza infection in mice.
AB  - BACKGROUND: Protein energy malnutrition (PEM), a common cause of secondary immune
      deficiency in children, is associated with an increased risk of infections. Very
      few studies have addressed the relevance of PEM as a risk factor for influenza.
      METHODS: We investigated the influence of PEM on susceptibility to, and immune
      responses following, influenza virus infection using isocaloric diets providing
      either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model.
      RESULTS: We found that mice maintained on the VLP diet, when compared to mice fed
      with the AP diet, exhibited more severe disease following influenza infection
      based on virus persistence, trafficking of inflammatory cell types to the lung
      tissue, and virus-induced mortality. Furthermore, groups of mice maintained on
      the VLP diet showed significantly lower virus-specific antibody response and a
      reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice
      fed on the AP diet. Importantly, switching diets for the group maintained on the
      VLP diet to the AP diet improved virus clearance, as well as protective immunity
      to viral challenge. CONCLUSIONS: Our results highlight the impact of protein
      energy on immunity to influenza infection and suggest that balanced protein
      energy replenishment may be one strategy to boost immunity against influenza
      viral infections.

PMID- 22949307
TI  - Association between transfusion with human herpesvirus 8 antibody-positive blood
      and subsequent mortality.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda and transmissible by
      blood. We evaluated mortality following transfusion of HHV-8 antibody-positive
      blood. METHODS: In a hospital-based, observational, prospective cohort study with
      a 6-month follow-up, we examined the effect of HHV-8 antibody-positive blood on
      transfusion recipients surviving at least 7 days. RESULTS: Of 1092 recipients,
      471 (43.1%) were transfused with HHV-8 antibody-positive blood. Median age was
      1.8 years (range, 0.1-78); 111 (10.2%) died during follow-up. After adjusting for
      confounders (increasing age, human immunodeficiency virus infection, illness
      other than malaria, receipt of multiple transfusions), recipients of HHV-8
      antibody-positive blood stored <=4 days ("short-stored") were more likely to die
      than recipients of HHV-8 antibody-negative blood (adjusted hazards ratio [AHR],
      1.92; 95% confidence interval [CI], 1.21-3.05; P = .01). The AHR of the effect of
      each additional short-stored HHV-8 antibody-positive transfusion was 1.79 (95%
      CI, 1.33-2.41; P = .001). CONCLUSIONS: Transfusion with short-stored HHV-8
      antibody-positive blood was associated with an increased risk of death. Further
      research is warranted to determine if a causal pathway exists and to verify the
      observed association between acute HHV-8 infection and premature mortality.

PMID- 22949309
TI  - Diagnosis of invasive pulmonary aspergillosis in children with bronchoalveolar
      lavage galactomannan.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a life-threatening
      complication in immunocompromised patients. Early diagnosis and therapy improves
      outcome. Assessment of galactomannan (GM) in bronchoalveolar lavage (BAL) fluid
      is a proposed tool to diagnose IPA. Little is known about the diagnostic value of
      BAL GM in children. MATERIALS AND METHODS: Retrospectively, 72 bronchoscopies
      were analyzed for GM in patients fulfilling the host factor criteria as defined
      by the EORTC/MSG. A cut-off index value GM of >=0.5 was used. Clinical data,
      results of chest CT-scans and BAL cultures were collected. RESULTS: Sensitivity,
      specificity, PPV, and NPV of BAL GM for a diagnosis of proven and probable IPA (n
      = 41) were 82.4%, 87.5%, 82.4%, and 87.5% respectively. A significant relation
      was found for BAL GM and abnormal chest CT (P = 0.01). No significant
      relationship was observed between BAL Aspergillus sp. culture and chest CT (n =
      47). BAL GM and serum GM correlated significantly. In 9 out of 12 patients
      classified as possible IPA, antifungal therapy was continued or started, despite
      a negative BAL GM. CONCLUSIONS: BAL GM test had good diagnostic value in children
      suspected of IPA. However, the decision to continue or start antifungal therapy
      was mainly determined by the clinical suspicion of IPA based on chest CT-outcome,
      serum GM index values and failure of antibiotic therapy.

PMID- 22949308
TI  - Impaired hepatitis C virus (HCV)-specific interferon-gamma responses in
      individuals with HIV who acquire HCV infection: correlation with CD4(+) T-cell
      counts.
AB  - Studies examining the effect of coinfection with human immunodeficiency virus
      (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute
      HCV infection are limited. This study directly compared acute HCV-specific T-cell
      responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV
      monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C
      (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in
      vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on
      the HCV-specific cytokine production in acute HCV infection, particularly on HCV
      specific interferon gamma (IFN-gamma) production (magnitude P = .004; breadth P =
      .046), which correlated with peripheral CD4(+) T-cell counts (rho = 0.605; P =
      .005) but not with detectable HIV viremia (rho = 0.152; P = .534).

PMID- 22949310
TI  - Human mesenchymal stem cells: a bank perspective on the isolation,
      characterization and potential of alternative sources for the regeneration of
      musculoskeletal tissues.
AB  - The continuous discovery of human mesenchymal stem cells (hMSCs) in different
      tissues is stirring up a tremendous interest as a cell source for regenerative
      medicine therapies. Historically, hMSCs have been always considered a sub
      population of mononuclear cells present in the bone marrow (BM). Although BM
      hMSCs are still nowadays considered as the most promising mesenchymal stem cell
      population to reach the clinics due to their capacity to differentiate into
      multiple tissues, hMSCs derived from other adult and fetal tissues have also
      demonstrated to possess similar differentiation capacities. Furthermore,
      different reports have highlighted a higher recurrence of hMSCs in some of these
      tissues as compared to BM. This offer a fascinating panorama for cell banking,
      since the creation of a stem cell factory could be envisioned where hMSCs are
      stocked and used for ad hoc clinical applications. In this review, we summarize
      the main findings and state of the art in hMSCs isolation, characterization, and
      differentiation from alternative tissue sources and we attempt to compare their
      potency for musculoskeletal regeneration.

PMID- 22949311
TI  - Elution behavior of short dsDNA strands in silicon micropillar array columns in
      ion pair reversed-phase chromatography mode.
AB  - In the present paper, dsDNA separation has been studied in a silicon micropillar
      array column using ion-pair RP-HPLC (IP-RP-HPLC). The deep-etched (32.0 MUm)
      silicon micropillar array was fabricated by advanced deep UV lithography and by a
      dedicated Bosch etch process and then sealed by anodic bonding to a Pyrex glass.
      The pillar surface was subsequently conditioned hydrophobic. Working in isocratic
      mode under nonretained conditions, van Deemter curves of dsDNA and coumarin were
      established to assess the performance of the micropillar array column, resulting
      in plate heights of only a few micrometers. Working in gradient mode, separations
      of dsDNA fragments were evaluated. The relevant gradient operation parameters
      were studied to understand their influence on dsDNA separations. The correlation
      between DNA length and retention was measured and theoretically described in a
      length range of 50-500 bp, promising for the determination of DNA of an unknown
      length. Finally, a separation example demonstrated the excellent separation power
      of on-chip IP-RP chromatography by achieving a large operation range of DNA
      length (10-300 bp) with a 5-bp difference among 11 dsDNA fragments.

PMID- 22949313
TI  - Ambulatory Monitoring of Preterm Infant During Their First Year of Life at the
      Pediatric Deparment of Cocody Teaching Hospital.
AB  - The prematurity remains in our developing countries a problem of current events.
      The deficiency in human resources and the low level of the technical equipment
      exposes premature babies to a high risk of morbidity and mortality in neonatal
      period. Those who survive need a closer follow-up after their discharge from
      hospital. Our objective through this study was to appreciate the quality of
      following-up premature babies in ambulatory. It was a longitudinal study with
      descriptive aim which took place from January, 2007 till December, 2008 in the
      paediatric service of the Teaching Hospital of Cocody. Our population was
      constituted by 100 premature babies selected in a random way. The premature
      babies had on average 31,7 weeks of gestationel age. The sex ratio was 0,96. The
      born weight was between 900 and 2550g. The main causes of prematurity were
      multiple pregnancies (18 %), malaria (15 %), premature break of membranes (12 %)
      and eclampsia (10 %). Most of premature babies were hospitalized for a problem of
      breeding ( 47 %.). The average number of consultation was 6,25. Only 25 children
      were effectively followed during 12 months with a middleweight of 9112g. The
      follow-up had been interrupted before 3 months of native age in 31 % of cases and
      before 3 months of real age in 52 % of cases. The mothers had preferred the
      feeding in 48 % of cases, but the curves of weight development were superposables
      whatever the type of food supply. The pathology during the follow-up was
      dominated by digestive disorders, respiratory infections and anaemia. Forty
      percent of the premature babies was able to have an haemoglobin test and 8 %, a
      neuroradiological scraeming. A third of the premature babies (30 %) had been
      hospitalized again for anaemia (10 %) and respiratory infections (10 %). We
      recorded 3 deaths.  CONCLUSION:  The follow-up of premature babies getting out of
      hospital remains difficult in our context of life. The mothers must be sensitived
      on the consequences of prematurity and the importance of their follow-up. This
      follow-up has to be the affair of all, as well parents, health workers that
      government.

PMID- 22949314
TI  - Surface chemical and physical modification in stent technology for the treatment
      of coronary artery disease.
AB  - Coronary artery disease (CAD) kills millions of people every year. It results
      from a narrowing of the arteries (stenosis) supplying blood to the heart. This
      review discusses the merits and limitations of balloon angioplasty and stent
      implantation, the most common treatment options for CAD, and the pathophysiology
      associated with these treatments. The focus of the review is heavily placed on
      research efforts geared toward the modification of stent surfaces for the
      improvement of stent-vascular compatibility and the reduction in the occurrence
      of related pathophysiologies. Such modifications may be chemical or physical,
      both of which are surveyed here. Chemical modifications may be passive or active,
      while physical modification of stent surfaces can also provide suitable
      substrates to manipulate the responses of vascular cells (endothelial, smooth
      muscle, and fibroblast). The influence of micro- and nanostructured surfaces on
      the in vitro cell response is discussed. Finally, future perspectives on the
      combination of chemical and physical modifications of stent surfaces are also
      presented.

PMID- 22949315
TI  - Reply: To PMID 22563589.

PMID- 22949318
TI  - Emerging new roles of Th17 cells.

PMID- 22949319
TI  - Human Th17 subsets.
AB  - Since their discovery as a distinct T helper (Th) cell lineage, Th17 cells have
      been extensively investigated both in mice and in humans. These studies have
      identified factors involved in their differentiation and effector functions and
      have also revealed a high degree of flexibility that seems to be a characteristic
      of the Th17-cell lineage. In this review, we discuss recent studies addressing
      the heterogeneity of human Th17 cells, their differentiation requirements, their
      migratory capacities, and their role in defense against fungi and extracellular
      bacteria.

PMID- 22949320
TI  - IL-17-producing gammadelta T cells and innate lymphoid cells.
AB  - The inflammatory cytokine IL-17 plays a critical role in immunity to infection
      and is involved in the inflammatory pathology associated with certain autoimmune
      diseases, such as psoriasis and rheumatoid arthritis. While CD4(+) and CD8(+) T
      cells are important sources of this cytokine, recent evidence has suggested that
      gammadelta T cells and a number of families of innate lymphoid cells (ILCs) can
      secrete IL-17 and related cytokines. The production of IL-17 by gammadelta T
      cells appears to be largely independent of T-cell receptor activation and is
      promoted through cytokine signalling, in particular by IL-23 in combination with
      IL-1beta or IL-18. Therefore IL-17-secreting gammadelta T cells can be
      categorised as a family of cells similar to innate-like lymphoid cells. IL-17
      secreting gammadelta T cells function as a part of mucosal defence against
      infection, with most studies to date focusing on their response to bacterial
      pathogens. gammadelta T cells also play a pathological role in certain autoimmune
      diseases, where they provide an early source of IL-17 and IL-21, which initiate
      responses mediated by conventional IL-17-secreting CD4(+) T cells (Th17 cells).
      ILCs lack an antigen receptor or other lineage markers, and ILC subsets that
      express the transcriptional factor RORgammat have been found to secrete IL-17.
      Evidence is emerging that these newly recognised sources of IL-17 play both
      pathological and protective roles in inflammatory diseases as discussed in this
      article.

PMID- 22949321
TI  - Small molecule inhibitors of RORgammat: targeting Th17 cells and other
      applications.
AB  - Nuclear hormone receptors (NHRs) form a family of transcription factors that are
      composed of modular protein structures with DNA- and ligand-binding domains (DBDs
      and LBDs). The DBDs confer gene target site specificity, whereas LBDs serve as
      control switches for NHR function. For many NHRs, both endogenous and synthetic
      small molecule ligands bind to small pockets within the LBDs, resulting in
      conformational changes that regulate transcriptional activity. This property of
      NHRs has been exploited by the pharmaceutical industry for therapeutic targeting
      of a wide variety of diseases, ranging from inflammatory diseases and cancer to
      endocrine and metabolic diseases. Th17 cells are CD4(+)  T helper effector cells
      that express several pro-inflammatory cytokines, including IL-17A, and the
      actions of these cells have been linked to multiple human autoimmune diseases.
      Our laboratory previously identified the NHR RORgammat, an immune cell-specific
      isoform of RORgamma (retinoic acid receptor-related orphan nuclear receptor
      gamma), as a key transcription factor for the development of Th17 cells both in
      human and mouse. Although endogenous ligands for RORgammat have not yet been
      reported, it is thought that RORgammat activity and Th17-cell development can be
      modulated with highly specific small molecules that bind to the RORgammat LBD and
      displace its endogenous ligands. Recent studies from multiple groups have
      reported the activities of such inhibitors. In this mini review, we describe how
      RORgammat inhibitors were identified and how they may contribute to our
      understanding about RORgammat and its biology.

PMID- 22949322
TI  - Life, death, and miracles: Th17 cells in the intestine.
AB  - Th17 cells, a distinct subset of CD4(+)  T-helper cells, are commonly associated
      with chronic inflammatory and autoimmune diseases; however, Th17 cells also
      possess a variety of beneficial functions as they maintain and defend mucosal
      barriers against pathogens and promote tissue repair. Furthermore, recent
      findings indicate that Th17 cells can also acquire immunosuppressive functions
      that protect against inflammatory and auto-immune diseases. A sentinel population
      of Th17 cells is localized in the intestine in the absence of pathology and, in
      response to infection, this population expands in number, and can also modulate
      its functions. This review discusses the beneficial and pathogenic roles played
      by Th17 cells in the intestine.

PMID- 22949324
TI  - A role for Th17 cells in the regulation of tertiary lymphoid follicles.
AB  - Immune responses propagate in secondary lymphoid organs (SLOs), such as the
      spleen and lymph nodes. These highly organized structures are typified by
      distinct B-cell follicles and T-cell zones, and are orchestrated by interactions
      between the TNF superfamily molecules expressed on hematopoietic cells and their
      receptors on mesenchymal cells and the subsequent cytokines and chemokines that
      are elicited. During chronic immune responses, cellular effectors of the immune
      response can infiltrate target tissue and organize anatomically into de novo B
      cell follicles and T-cell areas, a phenomenon called lymphoid neogenesis or the
      formation of tertiary lymphoid organs (TLOs). Critical to the development of SLOs
      are lymphoid-tissue inducer (LTi) cells, that is innate lymphoid cells that arise
      from common precursor cells within the fetal liver. Of interest, Th17 cells, a
      subset of CD4(+)  T cells most associated with autoimmune pathogenesis, share
      many developmental and effector markers with LTi cells. Here, we compare and
      contrast LTi and Th17 cells, and review recent evidence that Th17 cells and Th17
      cytokines, such as IL-17 and IL-22, contribute to the development of ectopic
      lymphoid structures in chronic-ally inflamed tissue.

PMID- 22949325
TI  - IL-23: one cytokine in control of autoimmunity.
AB  - During the past decade, it has been firmly established that IL-23 is essential
      for disease development in several models of autoimmune disease, including
      psoriatic skin inflammation, inflammatory bowel disease (IBD), and experimental
      autoimmune encephalomyelitis (EAE). The mechanism by which IL-23 exerts its
      pathogenic role has been mostly scrutinized in the context of Th17 cells, which
      were thought to mediate autoimmunity by secretion of IL-17 family cytokines.
      However, the picture emerging now is one of multiple IL-23-responsive cell types,
      pro-inflammatory cytokine induction, and pathogenic "licensing" following an IL
      23-dominated interaction between the T cell and the antigen-presenting cell
      (APC). This review will focus on our changing view of IL-23-dependent autoimmune
      pathologies with a particular emphasis on the responder cells and their IL-23
      induced factors that ultimately mediate tissue destruction.

PMID- 22949323
TI  - Immunity to infection in IL-17-deficient mice and humans.
AB  - Mice with defective IL-17 immunity display a broad vulnerability to various
      infectious agents at diverse mucocutaneous surfaces. In humans, the study of
      patients with various primary immunodeficiencies, including autosomal dominant
      hyper-IgE syndrome caused by dominant-negative STAT3 mutations and autosomal
      recessive autoimmune polyendocrinopathy syndrome type 1 caused by null mutations
      in AIRE, has suggested that IL-17A, IL-17F and/or IL-22 are essential for
      mucocutaneous immunity to Candida albicans. This hypothesis was confirmed by the
      identification of rare patients with chronic mucocutaneous candidiasis (CMC) due
      to autosomal recessive IL-17RA deficiency and autosomal dominant IL-17F
      deficiency. Heterozygosity for gain-of-function mutations in STAT1 in additional
      patients with CMC was recently shown to inhibit the development of IL-17 T cells.
      Although the infectious phenotype of patients with CMC and inborn errors of IL-17
      immunity remains to be finely delineated, it appears that human IL-17A and IL-17F
      display redundancy for protective immunity in natural conditions that is not seen
      in their mouse orthologs in experimental conditions.

PMID- 22949326
TI  - IL-17: a new actor in IFN-driven systemic autoimmune diseases.
AB  - Systemic autoimmune diseases such as systemic lupus erythematosus are type I IFN
      driven diseases with exaggerated B-cell responses and autoantibody production.
      Th17 cells, a T-helper-cell subset with high inflammatory capacity, was initially
      discovered and characterized in the context of experimental autoimmune
      encephalomyelitis - an animal model of multiple sclerosis. There is now emerging
      evidence that Th17 cells, and more generally IL-17 and IL-17-producing cells, may
      play a role in the pathogenesis of type I IFN-driven systemic autoimmune diseases
      such as lupus. Here, we review the different studies suggesting a role for IL-17
      and IL-17-producing cells in systemic autoimmune diseases, both in humans and in
      animal models, and we consider the possible mechanisms by which these cells may
      contribute to disease. We also discuss the hypothesis that type I IFN and IL-17
      act in concert to sustain and amplify autoimmune and inflammatory responses,
      making them a dangerous combination involved in the pathogenesis of systemic
      autoimmune diseases.

PMID- 22949327
TI  - T-cell exhaustion due to persistent antigen: quantity not quality?
AB  - T-cell exhaustion is characterized by failure to respond to a persistent antigen
      and is a hallmark of chronic infections and cancer. Here, we discuss several
      recent reports on T-cell exhaustion, including one in this issue of the European
      Journal of Immunology where Richter et al. [Eur. J. Immunol. 42:2290-2304]
      examine the importance of the amount of persistent antigen versus the cell type
      presenting it to induce CD8(+)  T-cell exhaustion, and the consequences for host
      survival during chronic viral infection.

PMID- 22949330
TI  - Semi-synthesis and biological evaluation of 1,2,3-triazole-based podophyllotoxin
      congeners as potent antitumor agents inducing apoptosis in HepG2 cells.
AB  - A series of 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners
      were synthesized by employing click chemistry and further evaluated for their
      antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22,
      and 24) exhibited approximately 100-fold more potent inhibitory activity against
      four tumor cell lines (HepG2, MKN-45, NCI-H1993, and B16) than etoposide as
      positive control. Docking studies on binding in the ATPase domain of
      topoisomerase II revealed perfect docking of four congeners in the active site.
      Furthermore, the podophyllotoxin congeners 10, 11, 12, and 13 induced cell cycle
      arrest of HepG2 cells at the G(2) /M phase in a concentration-dependent manner,
      assessed by flow cytometric analysis, highlighting that they exert their
      antitumor activity via HepG2 cell apoptosis.

PMID- 22949331
TI  - Changes in gastric pressure and volume during mechanical in-exsufflation.
AB  - BACKGROUND/PURPOSE: A mechanical insufflator-exsufflator (MI-E) is used to
      replicate spontaneous cough in weak or neurologically impaired patients. Its use
      is often withheld after abdominal surgery because of concerns for potential wound
      dehiscence from abdominal distension or development of excessive abdominal
      positive pressure. We hypothesized that gastric pressure during MI-E use would
      not exceed usual pressures generated during a spontaneous cough. METHODS:
      Thirteen subjects 0.8-23.1 years (mean 10.5 years) with neuromuscular weakness,
      pre-existing gastrostomy tube, and established MI-E routine were studied. A
      pressure transducer through the gastrostomy tube measured gastric pressure (Pgas)
      during MI-E treatment. Chest and abdominal volume change was assessed by
      respiratory inductance plethysmography. In three subjects, the same measurements
      were made during spontaneous cough. RESULTS: The maximum Pgas was 24 cm with
      applied pressures of 20-40 cm. In the three subjects able to cough, the maximum
      Pgas achieved during the spontaneous maneuver was 25 cm, a value higher than they
      achieved with MI-E treatment. CONCLUSION: MI-E resulted in less positive
      abdominal pressure than has been described in healthy subjects during spontaneous
      coughing. As such, use of an MI-E device should be considered safe to use in the
      post-operative period following abdominal surgery in patients with neuromuscular
      weakness.

PMID- 22949332
TI  - Optical microflow cytometer based on external total reflection.
AB  - A novel optical microflow cytometer based on external total reflection comprising
      a laser-induced fluorescence system, a PDMS chip, a plane mirror and a dichroic
      beamsplitter is proposed for the simultaneous detection, enumeration and sizing
      of labeled and nonlabeled microparticles. In the proposed approach, the total
      number and size of the particles passing through the detection region is
      determined via the nonscattered light signal reflected from a plane mirror
      positioned over the microchip, while the number of fluorescence-labeled particles
      is determined via the back scattered fluorescence signal. The experimental
      results confirm the ability of the proposed system to count and size fluorescent
      and nonfluorescent particles with nominal diameters ranging from 6 to 10.2 MUm.
      In addition, it is shown that for a mixed sample containing both labeled and
      nonlabeled particles, the number of nonlabeled particles can be determined by
      subtracting the number of peaks in the fluorescence signal from that in the
      reflected light signal.

PMID- 22949334
TI  - The dual roles of inflammatory cytokines and chemokines in the regulation of
      autoimmune diseases and their clinical implications.
AB  - Cytokines and chemokines are secreted, small cell-signaling protein molecules,
      whose receptors are expressed on immune cells. These factors play a critical role
      in immune cell differentiation, migration, and polarization into functional
      subtypes and in directing their biological functions. Much attention has been
      devoted to exploring the role of key inflammatory cytokines and promigratory
      chemokines in autoimmune, autoinflammatory, and allergic diseases, leading to
      development of therapeutic strategies that are based on their targeted
      neutralization. Recent studies, including those coming from our groups, show that
      several major proinflammatory cytokines and chemokines, including IFN-gamma, IL
      2, CCL2, and CXCL12, may also function as anti-inflammatory mediators and
      therefore, may have potential as anti-inflammatory drugs. Likewise, major anti
      inflammatory mediators, such as TGF-beta, may under certain conditions, in
      combination with other cytokines, exhibit proinflammatory function and direct the
      polarization of the highly inflammatory CD4(+) Th17 cells. We show here that the
      biological function of pro- and anti-inflammatory cytokines is dependent on three
      key parameters: the local concentration of a given cytokine, the stage of disease
      in which it is administered, and its combination with other cytokines. The
      therapeutic implications of these findings are discussed, including two very
      recent studies summarizing clinical trials, in which low-dose administration of
      IL-2 was used to successfully suppress HCV and GVHD.

PMID- 22949335
TI  - Evaluation of the Neuropad sudomotor function test as a screening tool for
      polyneuropathy in the elderly population with diabetes and pre-diabetes: the KORA
      F4 survey.
AB  - BACKGROUND: Neuropad is a novel indicator test for sudomotor dysfunction, which
      has not been validated as a screening tool in a population-based study. This
      study aimed to evaluate the utility of Neuropad as a screening tool for distal
      symmetric polyneuropathy among elderly subjects with diabetes and pre-diabetes in
      the general population. METHODS: Eligible subjects aged 61-82 years (n = 940)
      from the KORA F4 survey were examined, 201 of whom had diabetes and 231 had pre
      diabetes (WHO 1999 criteria). Polyneuropathy was defined by the Michigan
      Neuropathy Screening Instrument (MNSI) score >3. RESULTS: Polyneuropathy was
      diagnosed in 60 (29.9%) subjects with diabetes and in 45 (19.5%) subjects with
      pre-diabetes, respectively (p = 0.013). The sensitivity and negative predictive
      value of Neuropad (reading time: 10 min) for the diagnosis of polyneuropathy were
      moderately high, reaching 76.7% and 78.1% in subjects with diabetes and 57.8% and
      76.5% in those with pre-diabetes, respectively. Conversely, the specificity and
      positive predictive value for the diagnosis of polyneuropathy were rather low:
      35.5% and 33.6% in diabetic individuals and 33.3% and 17.3% in subjects with pre
      diabetes, respectively. Use of the >2 cut-off and MNSI combined with monofilament
      examination did not improve the diagnostic performance of Neuropad. CONCLUSIONS:
      In the elderly general population with diabetes and pre-diabetes, Neuropad has
      reasonable sensitivity but rather low specificity for the diagnosis of
      polyneuropathy. It is a useful simple and inexpensive tool to screen for and to
      exclude polyneuropathy as desired, while its low specificity implies that a
      longer reading time merits consideration.

PMID- 22949336
TI  - Rapid screening and determination of designer drugs in saliva by a nib-assisted
      paper spray-mass spectrometry and separation technique.
AB  - A method for the rapid screening and determination of amphetamine-type designer
      drugs in saliva by a novel nib-assisted paper spray-mass spectrometry procedure
      is described. Under optimized conditions, the limit of detections for amphetamine
      derivatives (model samples: o-, m-, p-chloroamphetamine and o-, m-, p
      fluoroamphetamine, respectively) were determined to 0.1 MUg/mL by the nib
      assisted paper spray-mass spectrometry method. This method is easier and has a
      higher sensitivity than similar methodologies, including atmospheric
      pressure/matrix-assisted laser desorption ionization mass spectrometry and
      electrospray-assisted laser desorption ionization/mass spectrometry. Data
      obtained using more classical separation methods, including liquid chromatography
      and capillary electrophoresis, are also reported.

PMID- 22949337
TI  - [In process citation].
AB  - INTRODUCTION: Myocardial infarction is a major emergency involving life
      threatening in the absence of appropriate treatment. The aim of this study was to
      analyze the problem of management of myocardial infarction in a second reference
      hospital in Mali. PATIENTS AND METHODS : This was a prospective descriptive study
      over a period of six months from January to June 2010. It concerned all patients
      admitted for myocardial infarction in intensive care.The diagnosis was suspected
      in chest pain or the occurrence of complications (PAO, cardiogenic shock) and
      electrocardiogram signs on at least two precordial leads. The parameters studied
      were: age,reason for admission, risk factors, hemodynamic parameters, the
      deadline for completion of the ECG, the topography of lesions and electrical
      changes within 15 days. RESULTS: A male was found with a mean age of 54.62 years.
      Chest pain was the main reason for admission (6 cases) followed by cardiogenic
      shock (1 case) and acute pulmonary edema (1 case). The electrocardiogram was
      performed in 7 patients more than 24 hours after admission. The anterior
      territory was the most affected. On admission three patients had a systolic
      pressure below 90 mmHg.The evolution was marked by occurred heart failure (3
      cases) and death (2 cases). CONCLUSION: The lack of diagnostic and therapeutic
      method in our heath facility helps to increase morbidity and mortality associated
      with myocardial infarction.

PMID- 22949338
TI  - The 'T' in ITP remains.

PMID- 22949339
TI  - A woman with a swollen uvula.

PMID- 22949340
TI  - The apples and oranges of cost-effectiveness: a rejoinder.

PMID- 22949341
TI  - The conundrum of cost-effectiveness.

PMID- 22949342
TI  - Flashing lights, floaters, and reduced vision.

PMID- 22949343
TI  - Fever, dyspnea, and hepatitis in an Iraq veteran.

PMID- 22949344
TI  - The role of aldosterone receptor antagonists in the management of heart failure:
      an update.
AB  - The aldosterone receptor antagonists (ARAs) spironolactone (Aldactone) and
      eplerenone (Inspra) have become part of standard medical therapy for heart
      failure, having shown clinical efficacy in randomized trials in patients with
      advanced symptomatic systolic heart failure, postinfarction heart failure with
      cardiac dysfunction, and systolic heart failure with mild symptoms. The benefits
      include a lower rate of death. Yet to be answered is whether the two drugs are
      clinically equivalent; another question is whether they may benefit everyone with
      symptomatic heart failure, including diastolic heart failure.

PMID- 22949345
TI  - Immune thrombocytopenia in adults: an update.
AB  - Immune thrombocytopenia (ITP) in adults is a chronic disease resulting from
      increased platelet destruction and impaired platelet production. Splenectomy
      remains the most effective and durable treatment in cases that are refractory to
      first-line therapy, but its use has declined because of the availability of
      alternate medical therapy, the associated risk of infection, and concern for
      surgery-related complications. Rituximab (Rituxan) may be an effective
      alternative but carries the risk of immunosuppression.

PMID- 22949346
TI  - Using the ankle-brachial index to diagnose peripheral artery disease and assess
      cardiovascular risk.
AB  - The ankle-brachial index is valuable for screening for peripheral artery disease
      in patients at risk and for diagnosing the disease in patients who present with
      lower-extremity symptoms that suggest it. The ankle-brachial index also predicts
      the risk of cardiovascular events, cerebrovascular events, and even death from
      any cause. Few other tests provide as much diagnostic accuracy and prognostic
      information at such low cost and risk.

PMID- 22949347
TI  - Is acetaminophen at daily doses of 2,000 mg and higher safe? Comment on the
      article by Hochberg et al.

PMID- 22949348
TI  - Can doping graphite trigger room temperature superconductivity? Evidence for
      granular high-temperature superconductivity in water-treated graphite powder.
AB  - Granular superconductivity in powders of small graphite grains (several tens of
      micrometers) is demonstrated after treatment with pure water. The temperature,
      magnetic field and time dependence of the magnetic moment of the treated graphite
      powder provides evidence for the existence of superconducting vortices with some
      similarities to high-temperature granular superconducting oxides but even at
      temperatures above 300 K. Room temperature superconductivity in doped graphite or
      at its interfaces appears to be possible.

PMID- 22949349
TI  - The effect of rotative stress on CAII, FAS, FASL, OSCAR, and TRAP gene expression
      in osteoclasts.
AB  - This study was designed to explore the effects of rotative stress on carbonic
      anhydrase II (CAII), TNF receptor superfamily member 6 (FAS), FAS ligand (FASL),
      osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase
      (TRAP) gene expression in osteoclasts. Osteoclasts were induced from RAW264.7
      cells cultured in medium containing recombinant murine soluble receptor activator
      of NF-Kbeta ligand (sRANKL). The mRNA and protein expression of CAII, FAS, FASL,
      OSCAR, and TRAP genes in osteoclasts was detected by RT-PCR and Western blot,
      respectively, after osteoclasts were loaded at various rotative stress strengths
      and times. No significant differences in mRNA and protein expression were
      observed between any of the control groups (P > 0.05). Importantly, rotative
      stress had a significant effect on the mRNA and protein expression of these genes
      (P < 0.05). We found a negative relationship between rotative stress strength and
      prolonged loading time and the expression of FAS/FASL genes in osteoclasts. In
      addition, there was a positive relationship between rotative stress strength and
      prolonged loading time and the expression of CAII, OSCAR, or TRAP genes in
      osteoclasts. Based on these results, rotative stress has a significant effect on
      CAII, FAS, FASL, OSCAR, and TRAP gene expression in osteoclasts.

PMID- 22949350
TI  - Lymphoscintigraphy in plastic bronchitis, a pediatric case report.
AB  - Plastic bronchitis (PB) is an uncommon, potentially fatal disease, marked by
      endobronchial cast formation causing variable degrees of respiratory distress.
      Primary and secondary pulmonary lymphatic abnormalities have been identified
      among the underlying mechanisms of cast formation. We present a case of PB where
      lymphoscintigraphy demonstrated the underlying lymphatic defect. A 6-year-old
      Hispanic male with congenital heart disease (CHD; post-Fontan) presented with
      recurrent pneumonia, respiratory distress. Bronchoscopy showed inflamed
      hypervascular mucosa and thick mucus plugs; no casts were seen. Later, PB was
      diagnosed after the patient expectorated a bronchial cast. Cast analysis showed
      lymphocytic aggregates with mucin and fibrin. Lymphoscintigraphy revealed
      abnormal lymphatic collaterals and retrograde trace reflux into the superior
      mediastinum, a picture consistent with thoracic duct lymph leakage into the
      tracheobronchial tree. The pathogenesis of PB is not fully understood, especially
      in patients with CHD. Chyle in bronchial casts suggests abnormal lymphatic flow.
      Reports of lymph flow abnormalities, especially endobronchial lymph leakage in
      CHD are limited. Lymphoscintigraphy in our case demonstrated clear evidence of
      retrograde lymph reflux and leakage into the bronchial tree. The case presented
      suggests that in some patients following Fontan surgery, high intrathoracic
      lymphatic pressure and retrograde lymph flow may contribute to recurrent cast
      formation. Finding the underlying lymphatic abnormality helps in specific case
      management. Lymphoscintigraphy is a safer and easier method than
      lymphangiography. Surgical lymphatic-venous shunting may be possible in select
      cases.

PMID- 22949351
TI  - Pseudopotentials for hybridized carbon atoms.
AB  - Pseudopotentials for hybridized atoms are extracted and combined. The study
      focuses on sp(2) carbon atoms and their combination to give rise to a pi
      electronic system. As electrons of interest are treated explicitly, any ab initio
      method can be used, thus, configuration interaction methods and time-dependent
      density functional theory are used and compared. All electron and pseudopotential
      calculations are in good agreement for electronic transition spectroscopy (0.2 eV
      difference), geometrical parameters (error of 0.8 pm), and reaction energies.

PMID- 22949352
TI  - Molecular characterization of prosomeric and intraprosomeric subdivisions of the
      embryonic zebrafish diencephalon.
AB  - During development of the early neural tube, positional information provided by
      signaling gradients is translated into a grid of transverse and longitudinal
      transcription factor expression domains. Transcription factor specification codes
      defining distinct histogenetic domains within this grid are evolutionarily
      conserved across vertebrates and may reflect an underlying common vertebrate
      bauplan. When compared to the rich body of comparative gene expression studies of
      tetrapods, there is considerably less comparative data available for teleost
      fish. We used sensitive multicolor fluorescent in situ hybridization to generate
      a detailed map of regulatory gene expression domains in the embryonic zebrafish
      diencephalon. The high resolution of this technique allowed us to resolve
      abutting and overlapping gene expression of different transcripts. We found that
      the relative topography of gene expression patterns in zebrafish was highly
      similar to those of orthologous genes in tetrapods and consistent with a three
      prosomere organization of the alar and basal diencephalon. Our analysis further
      demonstrated a conservation of intraprosomeric subdivisions within prosomeres 1,
      2, and 3 (p1, p2, and p3). A tripartition of zebrafish p1 was identified
      reminiscent of precommissural (PcP), juxtacommissural (JcP), and commissural
      (CoP) pretectal domains of tetrapods. The constructed detailed diencephalic
      transcription factor gene expression map further identified molecularly distinct
      thalamic and prethalamic rostral and caudal domains and a prethalamic eminence
      histogenetic domain in zebrafish. Our comparative gene expression analysis
      conformed with the idea of a common bauplan for the diencephalon of anamniote and
      amniote vertebrates from fish to mammals.

PMID- 22949353
TI  - [In process citation].
AB  - The binding of the horns takes a place growing among the various processes of
      birth-control. This binding of the horns is almost irreversible and the women who
      make recourse to this method are generally saddles which think of having achieved
      their families.

PMID- 22949354
TI  - Luminometer development in the last four decades: recollections of two
      entrepreneurs.
AB  - This article, written by two entrepreneurs in luminescence, traces their
      involvement in the major part of the interconnected innovation and development of
      luminometers, adenosine triphosphate (ATP) bioluminescence and other technologies
      from the mid-1970s to 2011 that ushered in much of the field of luminometry as we
      know it today. Key developments leading to current commercial applications of ATP
      bioluminescence, luminescence immunoassay, cellular luminescence, reporter gene
      and other applications are described from the first tube luminometers derived
      from early luminescence studies using liquid scintillation counting technology to
      measuring bioluminescence from crude ATP and firefly tail extracts.

PMID- 22949355
TI  - Determination of trace triclosan in environmental water by microporous bamboo
      activated charcoal solid-phase extraction combined with HPLC-ESI-MS.
AB  - A sensitive and efficient analytical method for triclosan (TCS) determination in
      water, which involves enrichment with bamboo-activated charcoal and detection
      with HPLC-ESI-MS, was developed. The influence of several operational parameters,
      including the eluant and its volume, the flow rate, the volume andacidity of the
      sample, and the amount of bamboo-activated charcoal, were investigated and
      optimized. Under the optimum conditions, linearity of the method was observed in
      the range of 0.02-20 MUg/L, with correlation coefficients (r(2) ) >0.9990. The
      limit of detection was 0.002 MUg/L based on the ratio of chromatographic signal
      to baseline noise (S/N = 3). The spiked recoveries of TCS in real water samples
      were achieved in the range of 97.6-112.5%. The proposed method was applied to
      analyze TCS in real aqueous samples. All the surface water samples collected in
      Xiaoqing River had detectable levels of TCS with concentrations of 42-197 ng/L.

PMID- 22949356
TI  - Simultaneous activation of p38 and JNK by arachidonic acid stimulates the
      cytosolic phospholipase A2-dependent synthesis of lipid droplets in human
      monocytes.
AB  - Exposure of human peripheral blood monocytes to free arachidonic acid (AA)
      results in the rapid induction of lipid droplet (LD) formation by these cells.
      This effect appears specific for AA in that it is not mimicked by other fatty
      acids, whether saturated or unsaturated. LDs are formed by two different routes:
      (i) the direct entry of AA into triacylglycerol and (ii) activation of
      intracellular signaling, leading to increased triacylglycerol and cholesteryl
      ester formation utilizing fatty acids coming from the de novo biosynthetic route.
      Both routes can be dissociated by the arachidonyl-CoA synthetase inhibitor
      triacsin C, which prevents the former but not the latter. LD formation by AA
      induced signaling predominates, accounting for 60-70% of total LD formation, and
      can be completely inhibited by selective inhibition of the group IVA cytosolic
      phospholipase A(2)alpha (cPLA(2)alpha), pointing out this enzyme as a key
      regulator of AA-induced signaling. LD formation in AA-treated monocytes can also
      be blocked by the combined inhibition of the mitogen-activated protein kinase
      family members p38 and JNK, which correlates with inhibition of cPLA(2)alpha
      activation by phosphorylation. Collectively, these results suggest that
      concomitant activation of p38 and JNK by AA cooperate to activate cPLA(2)alpha,
      which is in turn required for LD formation possibly by facilitating biogenesis of
      this organelle, not by regulating neutral lipid synthesis.

PMID- 22949357
TI  - Use of X-ray diffraction, molecular simulations, and spectroscopy to determine
      the molecular packing in a polymer-fullerene bimolecular crystal.
AB  - The molecular packing in a polymer: fullerene bimolecular crystal is determined
      using X-ray diffraction (XRD), molecular mechanics (MM) and molecular dynamics
      (MD) simulations, 2D solid-state NMR spectroscopy, and IR absorption
      spectroscopy. The conformation of the electron-donating polymer is significantly
      disrupted by the incorporation of the electron-accepting fullerene molecules,
      which introduce twists and bends along the polymer backbone and 1D electron
      conducting fullerene channels.

PMID- 22949358
TI  - Molecular biomarkers of colorectal cancer: prognostic and predictive tools for
      clinical practice.
AB  - Colorectal cancer remains one of the most common types of cancer and leading
      causes of cancer death worldwide. Although we have made steady progress in
      chemotherapy and targeted therapy, evidence suggests that the majority of
      patients undergoing drug therapy experience severe, debilitating, and even lethal
      adverse drug events which considerably outweigh the benefits. The identification
      of suitable biomarkers will allow clinicians to deliver the most appropriate
      drugs to specific patients and spare them ineffective and expensive treatments.
      Prognostic and predictive biomarkers have been the subjects of many published
      papers, but few have been widely incorporated into clinical practice. Here, we
      want to review recent biomarker data related to colorectal cancer, which may have
      been ready for clinical use.

PMID- 22949359
TI  - Simulation of biatrial conduction via different pathways during sinus rhythm with
      a detailed human atrial model.
AB  - In order to better understand biatrial conduction, investigate various conduction
      pathways, and compare the differences between isotropic and anisotropic
      conductions in human atria, we present a simulation study of biatrial conduction
      with known/assumed conduction pathways using a recently developed human atrial
      model. In addition to known pathways: (1) Bachmann's bundle (BB), (2) limbus of
      fossa ovalis (LFO), and (3) coronary sinus (CS), we also hypothesize that there
      exist two fast conduction bundles that connect the crista terminalis (CT), LFO,
      and CS. Our simulation demonstrates that use of these fast conduction bundles
      results in a conduction pattern consistent with experimental data. The comparison
      of isotropic and anisotropoic conductions in the BB case showed that the atrial
      working muscles had small effect on conduction time and conduction speed,
      although the conductivities assigned in anisotropic conduction were two to four
      times higher than the isotropic conduction. In conclusion, we suggest that the
      hypothesized intercaval bundles play a significant role in the biatrial
      conduction and that myofiber orientation has larger effects on the conduction
      system than the atrial working muscles. This study presents readers with new
      insights into human atrial conduction.

PMID- 22949360
TI  - Impairment of liver regeneration by the histone deacetylase inhibitor valproic
      acid in mice.
AB  - BACKGROUND AND OBJECTIVE: Liver regeneration is a complex process regulated by a
      group of genetic and epigenetic factors. A variety of genetic factors have been
      reported, whereas few investigations have focused on epigenetic regulation during
      liver regeneration. In the present study, valproic acid (VPA), a histone
      deacetylase (HDAC) inhibitor, was used to investigate the effect of HDAC on liver
      regeneration. METHODS: VPA was administered via intraperitoneal injection to 2/3
      partially hepatectomized mice to detect hepatocyte proliferation during liver
      regeneration. The mice were sacrificed, and their liver tissues were harvested at
      sequential time points from 0 to 168 h after treatment. DNA synthesis was
      detected via a BrdU assay, and cell proliferation was tested using Ki-67. The
      expressions of cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), and CDK4
      were detected by Western blot analysis. Chromatin immunoprecipitation (ChIP)
      assay was used to examine the recruitment of HDACs to the target promoter regions
      and the expression of the target gene was detected by Western blot. RESULTS:
      Immunohistochemical analysis showed that cells positive for BrdU and Ki-67
      decreased, and the peak of BrdU was delayed in the VPA-administered mice.
      Consistently, cyclin D1 expression was also delayed. We identified B-myc as a
      target gene of HDACs by complementary DNA (cDNA) microarray. The expression of B
      myc increased in the VPA-administered mice after hepatectomy (PH). The ChIP assay
      confirmed the presence of HDACs at the B-myc promoter. CONCLUSIONS: HDAC
      activities are essential for liver regeneration. Inhibiting HDAC activities
      delays liver regeneration and induces liver cell cycle arrest, thereby causing an
      anti-proliferative effect on liver regeneration.

PMID- 22949361
TI  - Impact of nodular size on the predictive values of gray-scale, color-Doppler
      ultrasound, and sonoelastography for assessment of thyroid nodules.
AB  - OBJECTIVE: To define the roles of gray-scale, color-Doppler ultrasound, and
      sonoelastography for the assessment of thyroid nodule to determine whether nodule
      size affects the differential diagnosis of benign and malignant. METHODS: A total
      of 243 consecutive subjects (214 women, 29 men) with 329 thyroid nodules were
      examined by gray-scale, color-Doppler ultrasound, and sonoelastography in this
      prospective study. All patients underwent surgery and the final diagnosis was
      obtained from histopathological examination. RESULTS: Three hundred and twenty
      nine nodules (208 benign, 121 malignant) were divided into small (SNs, 5-10 mm,
      n=137) and large (LNs, >10 mm, n=192) nodules. Microcalcifications were more
      frequent in malignant LNs than in malignant SNs, but showed no significant
      difference between benign LNs and SNs. Poorly-circumscribed margins were not
      significantly different between malignant SNs and LNs, but were less frequent in
      benign LNs than in benign SNs. Among all nodules, marked intranodular vascularity
      was more frequent in LNs than in SNs. By comparison, shape ratio of
      anteroposterior to transverse dimensions (A/T) >= 1 was less frequent in LNs than
      in SNs. Otherwise, among all nodules, marked hypoechogenicity and elasticity
      score of 4-6 showed no significant difference between LNs and SNs. CONCLUSIONS:
      The predictive values of microcalcifications, nodular margins, A/T ratio, and
      marked intranodular vascularity depend on nodule size, but the predictive values
      of echogenicity and elastography do not.

PMID- 22949362
TI  - Should few retrieved oocytes be as an indication for intracytoplasmic sperm
      injection?
AB  - OBJECTIVE: To reevaluate whether relatively few oocytes obtained in one cycle are
      an indication for intracytoplasmic sperm injection (ICSI). METHODS: A total of
      406 cycles with three or fewer retrieved oocytes performed in 396 non-male
      infertile couples were retrospectively reviewed. Cycles were classified into
      three groups by different fertilization techniques: the in vitro fertilization
      (IVF) group, insemination with conventional IVF; the ICSI group, insemination
      with ICSI though semen parameters were normal; and the rescue ICSI group, re
      insemination with ICSI after conventional IVF failure. RESULTS: The ICSI group
      resulted in higher normal fertilization compared with the conventional IVF group.
      Correspondingly, the cycle cancellation rate was decreased in the ICSI group,
      though it was not statistically significant. The clinical pregnancy rate and
      implantation rate were lower in the ICSI group compared with the conventional IVF
      group. Rescue ICSI was a method to avert total fertilization failure in
      conventional IVF, increasing fertilization and ensuring embryo availability for
      transfer, but the normal fertilization was the lowest due to delayed insemination
      and the chance of pregnancy was very little. CONCLUSIONS: Obtaining only few
      oocytes in one cycle is not considered as an indication for ICSI when the sperm
      sample is apparently normal. Rescue ICSI is either not recommended if
      conventional insemination fails. Such patients should not be subjected to the
      unnecessary costs and potential risks of ICSI.

PMID- 22949363
TI  - Effect of primary iris and ciliary body cyst on anterior chamber angle in
      patients with shallow anterior chamber.
AB  - OBJECTIVE: To evaluate the prevalence of primary iris and/or ciliary body cysts
      in eyes with shallow anterior chamber and their effect on the narrowing of the
      anterior chamber angle. METHODS: Among the general physical check-up population,
      subjects with shallow anterior chambers, as judged by van Herick technique, were
      recruited for further investigation. Ultrasound biomicroscope (UBM) was used to
      detect and measure the cysts located in the iris and/or ciliary body, the
      anterior chamber depth (ACD), the angle opening distance at 500 um (AOD500), and
      the trabecular-iris angle (TIA). A-scan ultrasonography was used to measure the
      ocular biometry, including lens thickness, axial length, lens/axial length factor
      (LAF), and relative lens position (RLP). The effect of the cyst on narrowing the
      corresponding anterior chamber angle and the entire angle was evaluated by the
      UBM images, ocular biometry, and gonioscopic grading. The eye with unilateral
      cyst was compared with the eye without the cyst for further analysis. RESULTS:
      Among the 727 subjects with shallow anterior chamber, primary iris and ciliary
      body cysts were detected in 250 (34.4%) patients; among them 96 (38.4%) patients
      showed unilateral single cyst, 21 (8.4%) patients had unilateral double cysts,
      and 42 (16.8%) patients manifested unilateral multiple and multi-quadrants cysts.
      Plateau iris configuration was found in 140 of 361 (38.8%) eyes with cysts. The
      mean size of total cysts was (0.6547 +/- 0.2319) mm. In evaluation of the effect
      of the cyst size and location on narrowing the corresponding angle to their
      position, the proportion of the cysts causing corresponding angle narrowing or
      closure among the cysts larger than 0.8 mm (113/121, 93.4%) was found to be
      significantly higher than that of the cysts smaller than 0.8 mm (373/801, 46.6%),
      and a significant higher proportion was also found in the cysts located at
      iridociliary sulcus (354/437, 81.0%) than in that at the pars plicata (131/484,
      27.1%). In evaluating the effect of the cyst on the entire anterior chamber
      angle, the eyes with multiple and multi-quadrants cysts manifested significant
      narrowing of the entire anterior chamber angle as compared with the eyes without
      cysts, based on the data analysis in comparison of TIA, AOD500, and gonioscopic
      grading evaluation. The unilateral single or double cysts in the eyes had no
      significant effect on narrowing of anterior chamber angle as compared with eyes
      without cysts. The iris and/or ciliary body cysts did not seem to affect the
      axial length, ACD, lens thickness, RLP, LAF. CONCLUSIONS: The prevalence of
      primary iris and ciliary body cyst was 34.4% in the subjects with shallow
      anterior chamber. The cysts larger than 0.8 mm, locating at iridociliary sulcus,
      or multiple and extensive cysts were inclined to cause the angle narrowing or
      closure.

PMID- 22949364
TI  - Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To review the efficacy and safety of rituximab therapy for systemic
      lupus erythematosus (SLE). METHODS: We searched for randomized controlled trails
      and observational studies that evaluated the effect of rituximab based on the
      systemic lupus erythematosus disease activity index (SLEDAI), British Isles lupus
      assessment group index (BILAG), urine protein levels, and the prednisolone dose,
      and had adequate data to calculate the mean, standard deviation (SD), and 95%
      confidence intervals, and to systematically review and meta-analyze observational
      studies with fixed effects model or random effects model. RESULTS: We included 2
      randomized controlled studies and 19 observational clinical studies. We
      summarized the data from the 19 observational studies, analyzed the heterogeneity
      of the literature, and then used fixed effect model or random effect model for
      statistical analysis. The SLEDAI, BILAG, and urine protein levels and the
      prednisolone dosage were decreased after rituximab treatment, and the decreases
      in the BILAG, urine protein levels, and the prednisolone dose were found to be
      significant (P<0.05), when compared with baseline level. Rituximab's adverse
      effects generally could be controlled with an effective dosing regimen.
      CONCLUSIONS: Although there are still controversies about rituximab's treatment
      on SLE, but our study had showed that rituximab had favorable effects on
      refractory lupus. The long-term efficacy and safety of rituximab require further
      study.

PMID- 22949365
TI  - Topical imiquimod treatment of cutaneous vascular disorders in pediatric
      patients: clinical evaluation on the efficacy and safety.
AB  - OBJECTIVE: To evaluate the clinical effect of topical imiquimod treatment on
      cutaneous vascular disorders in pediatric patients. METHODS: A retrospective
      investigation was conducted in 25 pediatric patients with cutaneous vascular
      disorders, including 19 infantile hemangiomas (IHs) (12 superficial/7 mixed
      type), 5 nevus flammeus (NF), and 1 pyogenic granuloma (PG). Imiquimod 5% cream
      was applied every other day for 4 to 16 weeks (average 9.6 weeks). RESULTS: Of
      the 19 IHs treated, an overall efficacy of 52.6% was achieved, with a clinical
      resolution rate of 15.8%, excellent rate of 26.3%, and moderate rate of 10.5%.
      The superficial type responded the best at 66.7%, while the mixed type showed
      only 28.6% effectiveness, which was predominantly from their superficial parts.
      No obvious response was noted in the 5 patients with NF. Side effects were
      observed in 78.9% of the patients, mostly mild to moderate local irritations and
      occasionally severe reactions such as thick crusting and ulceration. Systemic
      side events were observed in 4 IH patients including fever and digestive tract
      reactions. No recurrence was observed during the follow-up examination.
      CONCLUSIONS: Topical imiquimod could be an alternative option for the treatment
      of uncomplicated superficial IHs with satisfactory tolerability.

PMID- 22949366
TI  - High accuracy in automatic detection of atrial fibrillation for Holter
      monitoring.
AB  - Atrial fibrillation (AF) has been considered as a growing epidemiological problem
      in the world, with a substantial impact on morbidity and mortality. Ambulatory
      electrocardiography (e.g., Holter) monitoring is commonly used for AF diagnosis
      and therapy and the automated detection of AF is of great significance due to the
      vast amount of information provided. This study presents a combined method to
      achieve high accuracy in AF detection. Firstly, we detected the suspected
      transitions between AF and sinus rhythm using the delta RR interval distribution
      difference curve, which were then classified by a combination analysis of P wave
      and RR interval. The MIT-BIH AF database was used for algorithm validation and a
      high sensitivity and a high specificity (98.2% and 97.5%, respectively) were
      achieved. Further, we developed a dataset of 24-h paroxysmal AF Holter recordings
      (n=45) to evaluate the performance in clinical practice, which yielded
      satisfactory accuracy (sensitivity=96.3%, specificity=96.8%).

PMID- 22949367
TI  - A new plastic surgical technique for adult congenital webbed penis.
AB  - OBJECTIVE: To introduce a novel surgical technique for correction of adult
      congenital webbed penis. METHODS: From March 2010 to December 2011, 12 patients
      (age range: 14-23 years old) were diagnosed as having a webbed penis and
      underwent a new surgical procedure designed by us. RESULTS: All cases were
      treated successfully without severe complication. The operation time ranged from
      20 min to 1 h. The average bleeding volume was less than 50 ml. All patients
      achieved satisfactory cosmetic results after surgery. The penile curvature
      disappeared in all cases and all patients remained well after 1 to 3 months of
      follow-up. CONCLUSIONS: Adult webbed penis with complaints of discomfort or
      psychological pressure due to a poor profile should be indicators for surgery.
      Good corrective surgery should expose the glans and coronal sulcus, match the
      penile skin length to the penile shaft length dorsally and ventrally, and provide
      a normal penoscrotal junction. Our new technique is a safe and effective method
      for the correction of adult webbed penis, which produces satisfactory results.

PMID- 22949368
TI  - Emerging role of berbamine as an anti-cancer agent in systemic malignancies
      besides chronic myeloid leukemia.

PMID- 22949369
TI  - Severity scoring systems: are they internally valid, reliable and predictive of
      oxygen use in children with acute bronchiolitis?
AB  - BACKGROUND: Severity scores are commonly used in research and clinically to
      assess the severity of bronchiolitis. However, there are limitations as few have
      been validated. The aim of our study was to: (i) determine the validity and
      reliability of a bronchiolitis scoring system, and (ii) examine if the score
      predicted the need for oxygen at 12 and 24 hrs. Children aged <24 months
      presenting to Royal Darwin Hospital with a clinical diagnosis of bronchiolitis
      were eligible to participate. STUDY DESIGN: We reviewed published papers that
      used a bronchiolitis score and summarized the data in a table. We chose the Tal
      score that was easy to use and encompassed clinically important parameters. Three
      research nurses, trained to assess children, used two scoring systems (Tal and
      Modified-Tal; respiratory rate, accessory muscle use, wheezing, cyanosis, and
      oxygen saturation), blindly evaluated children within 15 min of each other.
      RESULTS: The children's (n = 115) median age was 5.4 months (IQR 2.9, 10.4); 65%
      were male and 64% were Indigenous. Internal consistency was excellent (Tal:
      Cronbach alpha = 0.66; Modified-Tal: alpha = 0.70). There was substantial inter
      rater agreement; weighted kappa of 0.72 (95% CI: 0.63, 0.83) for Tal and 0.70
      (95% CI: 0.63, 0.76) for Modified-Tal. For predicting requirement for oxygen at
      12 and 24 hrs; area under receiver operating curve (aROC) was 0.69 (95% CI: 0.13,
      1.0) and 0.75 (95% CI: 0.34, 1.0), respectively. CONCLUSION: The Tal and Modified
      Tal scoring systems for bronchiolitis is repeatable and can reliably be used in
      research and clinical practice. Its utility for prediction of O2 requirement is
      limited.

PMID- 22949371
TI  - Very efficient search for nucleotide alignments.
AB  - We describe a very efficient search for nucleotide alignments, which is analogous
      to the novel very efficient search for protein alignment. Just as it has been the
      case with the alignment of proteins, based on 20 * 20 adjacency matrices for
      amino acids, obtained from a superposition of labeled amino acids adjacency
      matrices for the proteins considered, one can construct labeled matrices of size
      4 * 4, listing adjacencies of nucleotides in DNA sequence. The matrix elements
      correspond to 16 pairs of adjacent nucleotides. To obtain DNA alignments, one
      combines information in the corresponding matrices for a pair of DNA nucleotides.
      Matrices are obtained by insertion of the sequential labels for pairs of
      nucleotides in the corresponding cells of the 4 * 4 tables. When two such
      matrices are superimposed, one can identify all segments in two DNA sequences,
      which are shifted relative to one another by the same amount in either direction,
      without using trial-and-error displacements of the two sequences one relative to
      the other to find local nucleotide alignments.

PMID- 22949370
TI  - Different affinity windows for virus and cancer-specific T-cell receptors:
      implications for therapeutic strategies.
AB  - T-cell destiny during thymic selection depends on the affinity of the TCR for
      autologous peptide ligands presented in the context of MHC molecules. This is a
      delicately balanced process; robust binding leads to negative selection, yet some
      affinity for the antigen complex is required for positive selection. All TCRs of
      the resulting repertoire thus have some intrinsic affinity for an MHC type
      presenting an assortment of peptides. Generally, TCR affinities of peripheral T
      cells will be low toward self-derived peptides, as these would have been
      presented during thymic selection, whereas, by serendipity, binding to pathogen
      derived peptides that are encountered de novo could be stronger. A crucial
      question in assessing immunotherapeutic strategies for cancer is whether natural
      TCR repertoires have the capacity for efficiently recognizing tumor-associated
      peptide antigens. Here, we report a comprehensive comparison of TCR affinities to
      a range of HLA-A2 presented antigens. TCRs that bind viral antigens fall within a
      strikingly higher affinity range than those that bind cancer-related antigens.
      This difference may be one of the key explanations for tumor immune escape and
      for the deficiencies of T-cell vaccines against cancer.

PMID- 22949372
TI  - Aptamers: a promising tool for cancer imaging, diagnosis, and therapy.
AB  - Aptamers are a group of molecules, which can specifically bind, track, and
      inhibit target molecules, comprising DNA aptamers, RNA aptamers, and peptide
      aptamers. So far, there are much progress about developing novel aptamers and
      their expansile applications. This prospect systematically introduces the
      composition and technological evolution of aptamers, and then focuses on the
      application of aptamers in cancer diagnosis, imaging, and therapy. Following
      this, we discuss the potential to harness aptamers in discovering the biomarker
      of stem cells, which is favorable for us to study the normal developmental or
      abnormal pathological process of tissue and to deliver drugs into target cells or
      tissues in the future.

PMID- 22949374
TI  - Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine
      hydrochloride.
AB  - The present monograph reviews data relevant to applying the biowaiver procedure
      for the approval of immediate release (IR) multisource solid dosage forms
      containing amodiaquine hydrochloride (ADQ) as the single active pharmaceutical
      ingredient (API). Both biopharmaceutical and clinical data of ADQ were assessed.
      Solubility studies revealed that ADQ meets the "highly soluble" criteria
      according to World Health Organization (WHO) and European Medicines Agency (EMA)
      but fails to comply with the United States Food and Drug Administration (US FDA)
      specifications. Although metabolism hints at high permeability, available
      permeability data are too scanty to classify ADQ inequivocably as a Class I drug
      substance. According to WHO and EMA guidances, ADQ would be conservatively
      categorized as a Class III drug, whereas according to the US FDA specifications,
      it would fall into Class IV. ADQ has a wide therapeutic index. Furthermore, no
      cases of bioinequivalent products have been reported in the open literature. As
      risks associated with biowaiving appear minimal and requirements for "highly
      soluble" API are met in the WHO and EMA jurisdictions, the biowaiver procedure
      can be recommended for bioequivalence (BE) testing of multisource IR products
      containing ADQ as the only API, provided the test product contains excipients
      used in ADQ products approved in International Conference of Harmonisation and
      associated countries, and in similar amounts. Furthermore, both comparator and
      test should conform to "very rapidly dissolving" product criteria (>=85%
      dissolution of the API in 15 min at pH 1.2, 4.5, and 6.8) and the labeling should
      specify that the product not be coadministered with high-fat meals. If the
      comparator and/or test product fails to meet these criteria, BE needs to be
      established by pharmacokinetic studies in humans.

PMID- 22949376
TI  - Aptasensor for amplified IgE sensing based on fluorescence quenching by graphene
      oxide.
AB  - Water-soluble graphene oxide (GO) with a two-dimensional layered nanostructure
      was synthesized and used as a quencher to construct a highly sensitive and
      selective fluorescence resonance energy transfer (FRET) aptasensor for sensing
      Immunoglobulin E (IgE). The fluorescein isothiocyanate (FITC)-labeled aptamer
      could be adsorbed stably onto the surface of GO via pi -> pi stacking
      interaction, which led to the occurrence of FRET from FITC to GO, and the
      fluorescence of FITC-labeled aptamer was quenched by GO via energy transfer. In
      the presence of IgE, the fluorescence was recovered due to a higher affinity
      between the aptamer and IgE compared with interactions between GO and the
      aptamer, leading to a high signal-to-background ratio. The fluorescence intensity
      of the aptamer increased in proportion to the amount of IgE in the sample,so that
      IgE could be detected with a linear range of 60-225 pM and a detection limit of
      22 pM. The assay was highly selective because the aptamer was unaffected by the
      presence of immunoglobulin G (IgG), human serum albumin (HSA) and bovine serum
      albumin (BSA). The practical application of the proposed aptasensor was
      successfully carried out for the determination of IgE in human serum samples.

PMID- 22949380
TI  - Measurement of barrier tissue integrity with an organic electrochemical
      transistor.
AB  - The integration of an organic electrochemical transistor with human barrier
      tissue cells provides a novel method for assessing toxicology of compounds in
      vitro. Minute variations in paracellular ionic flux induced by toxic compounds
      are measured in real time, with unprecedented temporal resolution and extreme
      sensitivity.

PMID- 22949379
TI  - A multifactorial likelihood model for MMR gene variant classification
      incorporating probabilities based on sequence bioinformatics and tumor
      characteristics: a report from the Colon Cancer Family Registry.
AB  - Mismatch repair (MMR) gene sequence variants of uncertain clinical significance
      are often identified in suspected Lynch syndrome families, and this constitutes a
      challenge for both researchers and clinicians. Multifactorial likelihood model
      approaches provide a quantitative measure of MMR variant pathogenicity, but first
      require input of likelihood ratios (LRs) for different MMR variation-associated
      characteristics from appropriate, well-characterized reference datasets.
      Microsatellite instability (MSI) and somatic BRAF tumor data for unselected
      colorectal cancer probands of known pathogenic variant status were used to derive
      LRs for tumor characteristics using the Colon Cancer Family Registry (CFR)
      resource. These tumor LRs were combined with variant segregation within families,
      and estimates of prior probability of pathogenicity based on sequence
      conservation and position, to analyze 44 unclassified variants identified
      initially in Australasian Colon CFR families. In addition, in vitro splicing
      analyses were conducted on the subset of variants based on bioinformatic splicing
      predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a
      colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44
      variants, the posterior probabilities of pathogenicity were such that altered
      clinical management would be indicated. Our findings provide a working
      multifactorial likelihood model for classification that carefully considers mode
      of ascertainment for gene testing.

PMID- 22949381
TI  - Hair zinc and selenium levels in children with recurrent wheezing.
AB  - The prevalence of asthma and other allergic diseases has increased markedly in
      the last few decades. Oxidative stress plays a central role in asthma
      pathogenesis, and reduced daily consumption of antioxidants is positively
      correlated with increased risk of asthma. Zinc (Zn) and selenium (Se) are the
      main antioxidant elements. In our study, we aimed to investigate hair Zn and Se
      levels in children with recurrent wheezing. The study included 65 patients with
      recurrent wheezing (RW) and 65 healthy children (HC). The hair Zn and Se levels
      (ug/g) of the RW group were lower in comparison with the HC group (162.43 +/-
      91.52 vs. 236.38 +/- 126.44, P < 0.001, and 217.37 +/- 83.01 vs. 280.53 +/-
      122.73, P < 0.001, respectively). Total antioxidant capacity (TAC) (mmol/L) of
      the RW group was found to be significantly lower in comparison with the HC group
      (1.38 +/- 0.14 vs. 1.53 +/- 0.20, respectively; P < 0.001). Number of wheezing
      episodes in the last 6 months were negatively correlated with serum TAC, hair Zn,
      and Se levels in RW group (r(p)  = -0.291, P = 0.001; r(p)  = -0.209, P = 0.017;
      r(p)  = -0.206, P = 0.019, respectively). The number of acute respiratory tract
      infection (ARTI) episodes in the last 6 months was negatively correlated with
      serum TAC and hair Zn levels (r(p)  = -0.316, P < 0.001, and r(p)  = -0.196, P =
      0.025, respectively). In this study, we found that TAC, hair Zn, and hair Se
      levels were lower in children with RW than HC and negatively correlated with
      wheezing episodes in the last 6 months. Also body Zn and Se levels can be
      reliably measured in hair samples.

PMID- 22949382
TI  - Appropriate description of intermolecular interactions in the methane hydrates:
      an assessment of DFT methods.
AB  - Accurate description of hydrogen-bonding energies between water molecules and van
      der Waals interactions between guest molecules and host water cages is crucial
      for study of methane hydrates (MHs). Using high-level ab initio MP2 and CCSD(T)
      results as the reference, we carefully assessed the performance of a variety of
      exchange-correlation functionals and various basis sets in describing the
      noncovalent interactions in MH. The functionals under investigation include the
      conventional GGA, meta-GGA, and hybrid functionals (PBE, PW91, TPSS, TPSSh,
      B3LYP, and X3LYP), long-range corrected functionals (omegaB97X, omegaB97, LC
      omegaPBE, CAM-B3LYP, and LC-TPSS), the newly developed Minnesota class
      functionals (M06-L, M06-HF, M06, and M06-2X), and the dispersion-corrected
      density functional theory (DFT) (DFT-D) methods (B97-D, omegaB97X-D, PBE-TS, PBE
      Grimme, and PW91-OBS). We found that the conventional functionals are not
      suitable for MH, notably, the widely used B3LYP functional even predicts
      repulsive interaction between CH(4) and (H(2)O)(6) cluster. M06-2X is the best
      among the M06-Class functionals. The omegaB97X-D outperforms the other DFT-D
      methods and is recommended for accurate first-principles calculations of MH. B97
      D is also acceptable as a compromise of computational cost and precision.
      Considering both accuracy and efficiency, B97-D, omegaB97X-D, and M06-2X
      functional with 6-311++G(2d,2p) basis set without basis set superposition error
      (BSSE) correction are recommended. Though a fairly large basis set (e.g., aug-cc
      pVTZ) and BSSE correction are necessary for a reliable MP2 calculation, DFT
      methods are less sensitive to the basis set and BSSE correction if the basis set
      is sufficient (e.g., 6-311++G(2d,2p)). These assessments provide useful guidance
      for choosing appropriate methodology of first-principles simulation of MH and
      related systems. (c) 2012 Wiley Periodicals, Inc.

PMID- 22949383
TI  - Novel starch-based PVA thermoplastic capsules for hydrophilic lipid-based
      formulations.
AB  - For decades, gelatin has been used in the rotary die process as a shell-forming
      material of soft capsules because of its unique physicochemical properties.
      However, with respect to the encapsulation of comparatively hydrophilic lipid
      based formulations, gelatin has one considerable drawback: Immediately after
      production, the capsule shell contains a large amount of water (up to 35%). There
      is the potential for water to migrate from the capsule shell into the
      formulation, which will lead to a decrease in drug solubility and, in turn, the
      potential for drug crystallization. The present study introduces a novel capsule
      material that was obtained from extrusion. The starch-based polyvinyl alcohol
      thermoplastic capsules (S-PVA-C) mainly comprised a blend of starch and PVA.
      Gelatin and the novel material were used to encapsulate a hydrophilic lipid-based
      system of fenofibrate. Considerable water migration was observed from the soft
      gelatin shell to the hydrophilic formulation during drying and drug
      crystallization resulted in soft gelatin capsules. In contrast, S-PVA-C displayed
      no substantial water exchange or drug crystallization upon storage. The
      thermoplastic capsule material further exhibited more surface roughness and
      higher resistance to mechanical deformation compared with gelatin. In conclusion,
      S-PVA-C provided a robust drug product following encapsulation of a rather
      hydrophilic lipid-based formulation.

PMID- 22949384
TI  - Celastrol attenuates adipokine resistin-associated matrix interaction and
      migration of vascular smooth muscle cells.
AB  - Obesity instigates various health problems such as atherosclerosis, diabetes, and
      cancer. Resistin, an adipose tissue-specific secretory adipokine, operates
      endocrine functions through increasing insulin resistance. Vascular smooth muscle
      cells (SMC) migrate into the subendothelial space and proliferate, thereby
      contributing to neointimal formation in atherosclerosis and restenosis. The aim
      of this study was to elucidate whether celastrol obtained from Tripterygium
      wilfordii Hook, inhibited human aortic SMC migration. Celastrol capable of
      antagonizing inflammatory responses attenuated the resistin secretion from THP-1
      derived macrophages. The macrophage-conditioned media promoted SMC proliferation
      and MMP-2 production, which was dampened by 10-100 nM celastrol. Celastrol
      encumbered the SMC migration in response to 50 ng/ml resistin, concomitant with
      the inhibition of induction of connective tissue growth factor and collagen I/IV.
      In addition, celastrol disabled human aortic SMC exposed to resistin from
      migrating. The resistin-induced shedding of integrin beta2/beta3 expression was
      demoted by celastrol, thereby contributing to the inhibition of collagen matrix
      SMC interaction. Next, resistin-induced Toll-like receptor-4 (TLR-4) expression
      was abrogated by celastrol, indicating that TLR-4 was the resistin signaling
      receptor that was blocked by celastrol. Collectively, these results demonstrate
      that anti-inflammatory celastrol blunted the macrophage secretion of the
      adipokine resistin, and suppressed the SMC migration by disturbing the
      interaction between SMC and intimal collagen matrix. Therefore, celastrol may
      inhibit atherogenic migration of vascular SMC upon resistin loading by intimal
      macrophages within atherosclerotic lesions.

PMID- 22949386
TI  - Preparation, characterization and luminescence properties of BiPO4 :Eu
      nanophosphors.
AB  - A facile chemical method was employed to prepare fine BiPO4 :Eu(3+) phosphor
      particles calcined at the same temperature. Introducing lithium greatly affected
      the morphology of the samples and further affected the luminescence intensity.
      The samples were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and photoluminescence (PL) spectroscopy. The XRD patterns of
      BiPO4 :Eu(3+) indicated a monoclinic phase. From the fluorescence spectra, the
      emission transition (5) D0  -> (7) F1 is more prominent than the normal red
      emission transition (5) D0  -> (7) F2 . Based on the intensity ratios of (5) D0  
      > (7) F2 to (5) D0  -> (7) F1 in the emission spectra, it can be concluded that
      introducing Li(+) can improve the symmetry of the crystal lattice and modify the
      emission intensity. Sharp lines at 395 nm are the strongest of the f-f
      transitions and match well with near-UV LED chips.

PMID- 22949388
TI  - Hazardous drinking among restaurant workers.
AB  - BACKGROUND/AIMS: We address three research questions pertaining to Swedish
      restaurant workers: (i) What is the prevalence of hazardous drinking? (ii) How is
      the consumption of alcohol distributed? (iii) Does the prevention paradox apply?
      METHODS: Data were collected by administering the Alcohol Use Disorders
      Identification Test (AUDIT) among restaurant workers who attended a 2-day
      Responsible Beverage Service training in Stockholm during the period from October
      2008 to December 2009. The control group comprised a sample representative of the
      general Swedish population. We restricted the analyses to the age span 18-59
      years, which yielded a sample size of 579 for restaurant workers and 434 for the
      general population. RESULTS: The prevalence of hazardous drinking as measured by
      AUDIT (8+ for men and 6+ for women) was markedly higher among restaurant workers
      than in the general population. The difference was especially pronounced among
      females below 30 years of age. We found no difference between restaurant workers
      and the general population in the distribution of alcohol consumption. About 76%
      of the drinking problems were found in the lower part of the consumption
      distribution (bottom 88%), which supports the prevention paradox. CONCLUSIONS:
      Restaurant workers comprise a high-risk group with respect to drinking.

PMID- 22949387
TI  - Calibration of multiple in silico tools for predicting pathogenicity of mismatch
      repair gene missense substitutions.
AB  - Classification of rare missense substitutions observed during genetic testing for
      patient management is a considerable problem in clinical genetics. The Bayesian
      integrated evaluation of unclassified variants is a solution originally developed
      for BRCA1/2. Here, we take a step toward an analogous system for the mismatch
      repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer
      susceptibility in Lynch syndrome by calibrating in silico tools to estimate prior
      probabilities of pathogenicity for MMR gene missense substitutions. A qualitative
      five-class classification system was developed and applied to 143 MMR missense
      variants. This identified 74 missense substitutions suitable for calibration.
      These substitutions were scored using six different in silico tools (Align
      Grantham Variation Grantham Deviation, multivariate analysis of protein
      polymorphisms [MAPP], MutPred, PolyPhen-2.1, Sorting Intolerant From Tolerant,
      and Xvar), using curated MMR multiple sequence alignments where possible. The
      output from each tool was calibrated by regression against the classifications of
      the 74 missense substitutions; these calibrated outputs are interpretable as
      prior probabilities of pathogenicity. MAPP was the most accurate tool and MAPP +
      PolyPhen-2.1 provided the best-combined model (R(2)  = 0.62 and area under
      receiver operating characteristic = 0.93). The MAPP + PolyPhen-2.1 output is
      sufficiently predictive to feed as a continuous variable into the quantitative
      Bayesian integrated evaluation for clinical classification of MMR gene missense
      substitutions.

PMID- 22949389
TI  - Dispersible surface-enhanced Raman scattering nanosheets.
AB  - Ultrathin and flexible silica nanosheets, synthesized with gold nanorod dimers
      embedded uniformly throughout, can be dispersed in solution and deposited onto
      arbitrary surfaces. These novel materials conform and maintain the as-synthesized
      density of dimers, allowing them to be used reliably in labeling and detection
      applications.

PMID- 22949390
TI  - Bronchoscopy and airway management in patients with mucopolysaccharidoses (MPS).
AB  - INTRODUCTION: Mucopolysaccharidoses (MPS) are a group of lysosomal storage
      disorders characterized by tissue deposition of glycosaminoglycans (GAG). Their
      musculoskeletal abnormalities and the GAG storage in the airway result in
      increased risk for patients undergoing anesthesia. This study evaluates a multi
      disciplinary airway management approach and reports upper and lower airway
      findings of flexible bronchoscopy performed during these procedures. METHODS:
      This is a retrospective study over 10 years evaluating approaches to and outcomes
      of airway management and bronchoscopic findings in this patient group. RESULTS:
      Thirty-one patients underwent a total of 105 anesthetic events of which 74
      involved multiple surgical services. The majority of patients were either MPS I
      (n = 9) or MPS II (n = 19). The median age was 8.6 years (range 1.1-24 years).
      Airway management by anesthesiologists alone occurred in 31 cases including
      natural airway (n = 7), perilaryngeal airway (n = 7), oral or nasal intubation (n
      = 7) or tracheostomy (n = 6) and emergent fiberoptic intubation in four cases. In
      74 of the procedures, flexible bronchoscopy was performed which included
      fiberoptic intubation in 22 cases. Post-operative complications occurred in eight
      cases mostly when prolonged airway instrumentation had occurred. The most
      frequent findings on bronchoscopy were GAG deposits/adenoid hypertrophy in 72%,
      laryngomalacia in 31% and lower airway deposits and/or tracheobronchomalacia in
      46% of procedures. Deposits of GAG were seen in patients as young as 4 years of
      age. CONCLUSION: Our experience demonstrates that a multidisciplinary approach
      and combined surgeries in MPS provides for safe airway management and allows
      diagnostic assessments for further patient care without added risks. Significant,
      multi-factorial airway compromise may occur already in early childhood including
      upper and lower airway GAG deposits.

PMID- 22949391
TI  - An assessment of pure, hybrid, meta, and hybrid-meta GGA density functional
      theory methods for open-shell systems: the case of the nonheme iron enzyme 8R
      LOX.
AB  - The performance of a range density functional theory functionals combined in a
      quantum mechanical (QM)/molecular mechanical (MM) approach was investigated in
      their ability to reliably provide geometries, electronic distributions, and
      relative energies of a multicentered open-shell mechanistic intermediate in the
      mechanism 8R-Lipoxygenase. With the use of large QM/MM active site chemical
      models, the smallest average differences in geometries between the catalytically
      relevant quartet and sextet complexes were obtained with the B3LYP(*) functional.
      Moreover, in the case of the relative energies between (4) II and (6) II, the use
      of the B3LYP(*) functional provided a difference of 0.0 kcal mol(-1). However,
      B3LYP(+/-) and B3LYP also predicted differences in energies of less than 1 kcal
      mol(-1). In the case of describing the electronic distribution (i.e., spin
      density), the B3LYP(*), B3LYP, or M06-L functionals appeared to be the most
      suitable. Overall, the results obtained suggest that for systems with multiple
      centers having unpaired electrons, the B3LYP(*) appears most well rounded to
      provide reliable geometries, electronic structures, and relative energies.

PMID- 22949392
TI  - Sinusoidal injury induction: monocrotaline dose and hepatic sinusoidal injury in
      rats not correlated.

PMID- 22949393
TI  - The influence of RAMP1 overexpression on CGRP-induced osteogenic differentiation
      in MG-63 cells in vitro: an experimental study.
AB  - The aim of this study was to elucidate the influence of receptor activity
      modifying protein 1 (RAMP1) overexpression on the expression and distribution of
      calcitonin receptor-like receptor (CRLR) in MG-63 cells. Our research also
      focused on whether RAMP1 overexpression enhanced the promoting effect of
      exogenous CGRP on osteogenic differentiation in MG-63 cells. We first constructed
      a eukaryotic expression vector containing human RAMP1 and stably transfected it
      into MG-63 cells. Real-time PCR and Western blotting were used to determine the
      expression levels of RAMP1 and CRLR mRNA and protein, respectively.
      Immunofluorescence analysis was employed to compare the distribution of CRLR in
      transfected cells. After treatment with CGRP, the extent of osteogenic
      differentiation was evaluated by simultaneous monitoring of alkaline phosphatase
      activity, the expression patterns of osteoblastic markers and mineralisation
      staining. We found that RAMP1 was more highly expressed in the transfected group
      compared with the control groups (P < 0.01). The CRLR expression was
      significantly higher than that in the control groups (P < 0.05). In addition,
      after 7 days of CGRP treatment to induce osteogenic differentiation, the
      expression of collagen I mRNA was markedly increased in the transfected group (P
      < 0.05). The transfected group exhibited more granular precipitation in the
      cytoplasm with alkaline phosphatase staining after 7 and 14 days of
      differentiation. When stained with Alizarin Red, cells overexpressing RAMP1 were
      darker and formed many mineralised nodules with clear boundaries and calcium
      deposition typical of mineralised bone matrix structures at 28 days post
      induction of differentiation. The CGRP-induced ALP activity in the RAMP1
      overexpression group was significantly higher 3, 6 and 9 days after induction
      than that in the two control groups (P < 0.05). RAMP1 overexpression promotes
      CRLR expression, localisation on the cell membrane and enhanced CGRP-mediated
      differentiation of MG-63 cells. This study contributes to a better understanding
      of the molecular mechanisms governing CGRP-induced MG-63 differentiation.

PMID- 22949394
TI  - A study on the interaction between 3-spiro-piperidones and bovine serum albumin
      using spectroscopic approaches.
AB  - The interaction between 3-spiro-2'-pyrrolidine-3'-spiro-3"-piperidine-2,3"-dione
      (PPD) and bovine serum albumin (BSA) in aqueous solution was studied using
      fluorescence and UV-vis spectroscopy. Fluorescence emission data revealed that
      BSA (1.00 * 10(-5)  mol/L) fluorescence was statically quenched by PPD at various
      concentrations, which implies that a PPD-BSA complex was formed. The binding
      constant (KA ), the number of binding sites (n) and the specific binding site of
      the PPD with BSA were determined. Energy-transfer efficiency parameters were
      determined and the mechanism of the interaction discussed. The thermodynamic
      parameters, DeltaG, DeltaH and DeltaS, were obtained according to van't Hoff's
      equation, showing the involvement of hydrophobic forces in these interactions.
      The effect of PPD acting on the BSA conformation was detected by synchronous
      fluorescence.

PMID- 22949395
TI  - Description of a large family with autosomal dominant hypercholesterolemia
      associated with the APOE p.Leu167del mutation.
AB  - Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia
      characterized by high cholesterol and triglycerides levels. Autosomal dominant
      hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9
      genes, is characterized by an isolated elevation of cholesterol due to the high
      levels of low-density lipoproteins (LDLs). We now report an exceptionally large
      family including 14 members with ADH. Through genome-wide mapping, analysis of
      regional/functional candidate genes, and whole exome sequencing, we identified a
      mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported
      associated with sea-blue histiocytosis and familial combined hyperlipidemia. We
      confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted
      destabilization of an alpha-helix in the binding domain, (2) a decreased apo E
      level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that
      mutations in the APOE gene can be associated with bona fide ADH.

PMID- 22949397
TI  - Oral intake of beet extract provides protection against skin barrier impairment
      in hairless mice.
AB  - The epidermis acts as a functional barrier against the external environment.
      Disturbances in the function of this barrier cause water loss and increase the
      chances of penetration by various irritable stimuli, leading to skin diseases
      such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical
      natural element of the protective epidermal barrier. The aim of this study was to
      evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural
      product rich in glucosylceramide (GlcCer), may prevent disturbance in skin
      barrier function. When HR-1 hairless mice were fed a special diet (HR-AD),
      transepidermal water loss (TEWL) from the dorsal skin increased, with a
      compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry
      skin with erythema and showed increased scratching behaviour. Histological
      examinations revealed a remarkable increase in the thickness of the skin at 8
      weeks. Supplemental addition of beet extract, which contained GlcCer at a final
      concentration of 0.1%, significantly prevented an increase TEWL, water intake,
      cumulative scratching time, and epidermal thickness at 8 weeks. These results
      indicate that oral intake of beet extract shows potential for preventing skin
      diseases associated with impaired skin barrier function.

PMID- 22949398
TI  - Outcomes of surgical management of severe GERD in patients with cystic fibrosis.
AB  - BACKGROUND: Patients with cystic fibrosis (CF) are at high risk for
      gastroesophageal reflux disease (GERD) and medical management of GERD improves
      pulmonary symptoms. Some patients with worsening CF and GERD symptoms undergo
      Nissen fundoplication, but the extent to which surgical management of GERD
      improves respiratory symptoms is not well studied. The purpose of this
      retrospective study was to evaluate the safety and efficacy of Nissen
      fundoplication in 48 patients with CF and uncontrolled GERD. RESULTS: Patients
      exhibited significantly fewer pulmonary exacerbations, increased weight gain and
      slower decline in % predicted FEV1 at 2 years after the surgery, compared to 2
      years before surgery. Mean change in % predicted FEV1 in 2 years before surgery
      was--13.57% and mean change in % predicted FEV1 in 2 years after the surgery was
      +1.5% and difference was significant P = 0.001. Better pulmonary and nutritional
      outcomes were noted among patients with milder lung disease compared to those
      with severe lung disease, and among patients who received gastrostomy tube
      feedings for >=6 months compared to those with no G-tube or tube feedings for <6
      months. There was no mortality associated with surgery. CONCLUSION: In CF
      patients with worsening lung disease and uncontrolled GERD, Nissen fundoplication
      not only slows the decline in lung function but leads to significant improvement
      in weight, and decrease in CF exacerbations. Patients with milder disease and
      patients receiving G-tube feedings for >=6 months after surgery benefited the
      most.

PMID- 22949399
TI  - Prediction of the rate of decline in fetal hemoglobin levels between first and
      second transfusions in red cell alloimmune disease.
AB  - OBJECTIVE: To determine variables that predict the rate of decline in fetal
      hemoglobin levels in alloimmune disease. METHOD: Retrospective review of
      singleton pregnancies that underwent first and second intrauterine transfusions
      for treatment of fetal anemia because of maternal Rh alloimmunization in a
      tertiary referral center. RESULTS: Forty-one first intrauterine transfusions were
      performed at 26.1 weeks (standard deviation, SD, 4.6), mean volume of blood
      transfused was 44.4 mL (SD 23.5) and estimated feto-placental volume expansion
      was 51.3% (SD 14.5%). Between first and second transfusion, hemoglobin levels
      reduced on average 0.40 g/dl/day (SD 0.25). Stepwise multiple regression analysis
      demonstrated that this rate significantly correlated with hemoglobin levels after
      the first transfusion, the interval between both procedures, and middle cerebral
      artery systolic velocity before the second transfusion. CONCLUSION: The rate of
      decline in fetal hemoglobin levels between first and second transfusions in
      alloimmune disease can be predicted by a combination of hemoglobin levels after
      the first transfusion, interval between both procedures, and middle cerebral
      artery systolic velocity before the second transfusion.

PMID- 22949400
TI  - The pattern and risk factors of recurrence of proximal gastric cancer after
      curative resection.
AB  - PURPOSE: To explore the time and pattern of recurrence of proximal gastric cancer
      and estimate the risk factors and prognostic factors for it. Considering these
      risk factors, postoperative adjuvant therapies and follow-up program can be
      individualized. METHODS: The data of 135 recurrence proximal gastric cancer
      patients were extracted and analyzed. RESULTS: In 135 recurrence patients, the
      median time to recurrence was 14.0 months, 116 (85.9%) patients had recurrences
      within 2 years. Loco-regional recurrence was the most prevalent pattern.
      Hematogenous metastasis was next prevalent pattern in which the liver was the
      most common organ. Peritoneal recurrence occurred in 32 patients. Five patients
      recurred in distant lymph nodes. The deeper invasion was associated with higher
      incidence of hematogenous metastases and peritoneal recurrence. The histological
      type, depth of invasion, and lymph node metastasis were independent risk factors
      for overall recurrence. While, negative lymph nodes counts were another
      independent risk factors for early recurrence. Patients with systemic recurrence
      and early recurrence patients had poorer prognosis. CONCLUSION: Total gastrectomy
      and adequate lymph nodes dissection were rational choice of proximal gastric
      cancer with deeper invasion. Pathologic predictors of invasion, histological
      type, lymph nodes metastasis and negative lymph node counts could guide
      individualized, risk-oriented adjuvant treatment, and follow-up plan.

PMID- 22949401
TI  - Secreted phosphoprotein-24 kDa (Spp24) attenuates BMP-2-stimulated Smad 1/5
      phosphorylation and alkaline phosphatase induction and was purified in a
      protective complex with alpha2 -Macroglobulins From Serum.
AB  - Secreted phosphoprotein-24 kDa (Spp24) binds cytokines of the bone morphogenetic
      protein/transforming growth factor-beta (BMP/TGFbeta) superfamily and is one of
      the most abundant serum phosphoproteins synthesized by the liver. Little is known
      about how Spp24 binding affects BMP signal transduction and osteoblastic
      differentiation or how this labile protein is transported from the liver to
      remote tissues, such as bone. When Spp24 was administered to W-20-17 mesenchymal
      stem cells with rhBMP-2, short-term Smad1/5 phosphorylation was inhibited,
      intermediate-term alkaline phosphatase (ALP) induction was blunted, and long-term
      mineralization was unaffected. This supports the hypothesis that Spp24
      proteolysis restricts the duration of its regulatory effects, but offers no
      insight into how Spp24 is transported intact from the liver to bone. When Spp24
      was immunopurified from serum and subjected to native PAGE and Western blotting,
      a high molecular weight band of >500 kDa was found. Under reducing SDS-PAGE, a 24
      kDa band corresponding to monomeric Spp24 was liberated, suggesting that Spp24 is
      bound to a complex linked by disulfide bonds. However, such a complex cannot be
      disrupted by 60 mM EDTA under non-reducing condition or in purification buffers
      containing 600 mM NaCl and 0.1% Tween-20 at pH 2.7-8.5. LC-MS/MS analysis of
      affinity-purified, non-reducing SDS-PAGE separated, and trypsin digested bands
      showed that the Spp24 was present in a complex with three alpha(2) 
      macroglobulins (alpha(2) -macroglobulin [alpha(2) M], pregnancy zone protein
      [PZP] and complement C3 [C3]), as well as ceruloplasmin and the protease
      inhibitor anti-thrombin III (Serpin C1), which may protect Spp24 from
      proteolysis.

PMID- 22949402
TI  - Revisited microanatomy of the corneal endothelial periphery: new evidence for
      continuous centripetal migration of endothelial cells in humans.
AB  - The control of corneal transparency depends on the integrity of its endothelial
      monolayer, which is considered nonregenerative in adult humans. In pathological
      situations, endothelial cell (EC) loss, not offset by mitosis, can lead to
      irreversible corneal edema and blindness. However, the hypothesis of a slow,
      clinically insufficient regeneration starting from the corneal periphery remains
      debatable. The authors have re-evaluated the microanatomy of the endothelium in
      order to identify structures likely to support this homeostasis model. Whole
      endothelia of 88 human corneas (not stored, and stored in organ culture) with
      mean donor age of 80 +/- 12 years were analyzed using an original flat-mounting
      technique. In 61% of corneas, cells located at the extreme periphery (last 200
      MUm of the endothelium) were organized in small clusters with two to three cell
      layers around Hassall-Henle bodies. In 68% of corneas, peripheral ECs formed
      centripetal rows 830 +/- 295 MUm long, with Descemet membrane furrows visible by
      scanning electron microscopy. EC density was significantly higher in zones with
      cell rows. When immunostained, ECs in the extreme periphery exhibited lesser
      differentiation (ZO-1, Actin, Na/K ATPase, CoxIV) than ECs in the center of the
      cornea but preferentially expressed stem cell markers (Nestin, Telomerase, and
      occasionally breast cancer resistance protein) and, in rare cases, the
      proliferation marker Ki67. Stored corneas had fewer cell clusters but more Ki67
      positive ECs. We identified a novel anatomic organization in the periphery of the
      human corneal endothelium, suggesting a continuous slow centripetal migration,
      throughout life, of ECs from specific niches.

PMID- 22949403
TI  - Erucin and benzyl isothiocyanate suppress growth of late stage primary human
      ovarian carcinoma cells and telomerase activity in vitro.
AB  - In the present study we analysed the effects of isothiocyanates (ITCs)--plant
      derived sulphur-containing constituents known for their potential
      chemotherapeutic activity--on growth inhibition and programmed death in primary
      ovarian carcinoma cells from ascites of human patients. Twenty-four hour exposure
      of carcinoma cells to 5-50 MUM erucin or benzyl ITC led to a concentration
      dependent viability loss, as determined by erytrosin B cell staining. This
      concurred with an increase in internucleosomal DNA fragmentation, mitochondrial
      membrane depolarization and downregulation of Akt as indicator for apoptosis
      induction. Cell accumulation at the G2/M phase was evident after 48 h of erucin
      treatment. Telomerase, a selective target of cancer cells, was suppressed by
      erucin. Although pre-treatment of cells with the thiol antioxidant N
      acetylcysteine could completely prevent initialization of the apoptotic process,
      it failed to abolish ITC-mediated telomerase suppression. Taken together, in our
      study, ITC exerted comparable cytotoxic efficacy against primary ovarian cancer
      cells as reported for corresponding cell lines. The clinical significance of this
      observation should be addressed in future studies and the role of telomerase
      further investigated.

PMID- 22949404
TI  - Clinical risk factors are more relevant than respiratory viruses in predicting
      bronchiolitis severity.
AB  - BACKGROUND: The role of respiratory viruses in the pathogenesis of bronchiolitis
      was re-evaluated with the use of molecular methods such as PCR for virus
      detection. Whether specific viruses or the classical clinical risk factors are
      more important in determining severe bronchiolitis is not well established. AIM:
      To analyze the specific viruses and clinical variables that can predict severe
      bronchiolitis at admission. METHODS: Nasopharyngeal aspirates were prospectively
      collected from 484 children <12 months admitted to the pediatrics ward or PICU at
      Universitary Hospital Sant Joan de Deu (Barcelona, Spain) for bronchiolitis from
      October 2007 to October 2008. Clinical and demographic data were collected.
      Sixteen respiratory viruses were studied using PCR. Severity was assessed with a
      bronchiolitis clinical score (BCS). RESULTS: Four hundred ten infants that tested
      positive for respiratory viruses were analyzed. Mixed viral infections did not
      increase the severity of the disease. Rhinovirus was associated with severe BCS
      in univariate analysis (P = 0.041), but in the multivariate logistic regression
      including viruses and clinical data only bronchopulmonary dysplasia (OR 7.2; 95%
      CI 1.2-43.3), congenital heart disease (OR 4.7; 95% CI 1.1-19.9), prematurity (OR
      2.6; 95% CI 1.3-5.1), and fever (OR 1.8, 95% CI 1.1-3.1) showed statistical
      significance for predicting severe BCS. CONCLUSIONS: Classical clinical risk
      factors have more weight in predicting a severe BCS in infants with acute
      bronchiolitis than the involved viruses.

PMID- 22949405
TI  - Fetotoxicity of 2,4-dichlorophenoxyacetic acid in rats and the protective role of
      vitamin E.
AB  - The present study was conducted to investigate the potential role of 2,4
      dichlorophenoxyacetic acid (2,4-D) in inducing developmental toxicity and
      oxidative damage in pregnant rats and their fetuses as well as to assess the
      efficacy of vitamin E to prevent or alleviate such defects. Pregnant rats
      received 2,4-D (100 mg/kg bw) alone or in combination with vitamin E (100 mg/kg
      bw) daily from gestation day 1 to 19. The number of implantations, viable and
      resorbed fetuses and sex ratio were not statistically different among groups.
      However, fetuses maternally treated with 2,4-D were characterized by lower body
      weight and higher morphologic and skeletal defect rate. 2,4-D induced oxidative
      stress in the liver of mothers and fetuses which was indicated by a significant
      elevation of malondialdehyde level with reduction in catalase activity and total
      antioxidant capacity. Coadministration of vitamin E can counteract the
      deleterious effects of 2,4-D by successive reduction in the oxidative stress. 

PMID- 22949406
TI  - Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary
      function partly via VEGF-VEGF receptors.
AB  - Progressive pulmonary inflammation and emphysema have been implicated in the
      progression of chronic obstructive pulmonary disease (COPD), while current
      pharmacological treatments are not effective. Transplantation of bone marrow
      mesenchymal stem cells (MSCs) has been identified as one such possible strategy
      for treatment of lung diseases including acute lung injury (ALI) and pulmonary
      fibrosis. However, their role in COPD still requires further investigation. The
      aim of this study is to test the effect of administration of rat MSCs (rMSCs) on
      emphysema and pulmonary function. To accomplish this study, the rats were exposed
      to cigarette smoke (CS) for 11 weeks, followed by administration of rMSCs into
      the lungs. Here we show that rMSCs infusion mediates a down-regulation of pro
      inflammatory mediators (TNF-alpha, IL-1beta, MCP-1, and IL-6) and proteases (MMP9
      and MMP12) in lung, an up-regulation of vascular endothelial growth factor
      (VEGF), VEGF receptor 2, and transforming growth factor (TGFbeta-1), while
      reducing pulmonary cell apoptosis. More importantly, rMSCs administration
      improves emphysema and destructive pulmonary function induced by CS exposure. In
      vitro co-culture system study of human umbilical endothelial vein cells
      (EA.hy926) and human MSCs (hMSCs) provides the evidence that hMSCs mediates an
      anti-apoptosis effect, which partly depends on an up-regulation of VEGF. These
      findings suggest that MSCs have a therapeutic potential in emphysematous rats by
      suppressing the inflammatory response, excessive protease expression, and cell
      apoptosis, as well as up-regulating VEGF, VEGF receptor 2, and TGFbeta-1.

PMID- 22949407
TI  - Mitochondrial superoxide production negatively regulates neural progenitor
      proliferation and cerebral cortical development.
AB  - Although high amounts of reactive oxygen species (ROS) can damage cells, ROS can
      also play roles as second messengers, regulating diverse cellular processes.
      Here, we report that embryonic mouse cerebral cortical neural progenitor cells
      (NPCs) exhibit intermittent spontaneous bursts of mitochondrial superoxide (SO)
      generation (mitochondrial SO flashes) that require transient opening of membrane
      permeability transition pores (mPTP). This quantal SO production negatively
      regulates NPC self-renewal. Mitochondrial SO scavengers and mPTP inhibitors
      reduce SO flash frequency and enhance NPC proliferation, whereas prolonged mPTP
      opening and SO generation increase SO flash incidence and decrease NPC
      proliferation. The inhibition of NPC proliferation by mitochondrial SO involves
      suppression of extracellular signal-regulated kinases. Moreover, mice lacking
      SOD2 (SOD2-/- mice) exhibit significantly fewer proliferative NPCs and
      differentiated neurons in the embryonic cerebral cortex at midgestation compared
      with wild-type littermates. Cultured SOD2-/- NPCs exhibit a significant increase
      in SO flash frequency and reduced NPC proliferation. Taken together, our findings
      suggest that mitochondrial SO flashes negatively regulate NPC self-renewal in the
      developing cerebral cortex.

PMID- 22949408
TI  - How can measurement, monitoring, modeling and control advance cell culture in
      industrial biotechnology?
AB  - This report highlights the potential of measurement, monitoring, modeling and
      control (M(3) C) methodologies in animal and human cell culture technology. In
      particular, state-of-the-art of M(3) C technologies and their industrial
      relevance of existing technology are addressed. It is a summary of an expert
      panel discussion between biotechnologists and biochemical engineers with both
      academic and industrial backgrounds. The latest ascents in M(3) C are discussed
      from a cell culture perspective for industrial process development and production
      needs. The report concludes with a set of recommendations for targeting M(3) C
      research toward the industrial interests. These include issues of importance for
      biotherapeutics production, miniaturization of measurement techniques and
      modeling methods.

PMID- 22949409
TI  - Lung transplantation for childhood diffuse lung disease.
AB  - BACKGROUND: Pediatric diffuse lung diseases comprise a heterogeneous group of
      rare lung disorders which may lead to end stage lung disease and referral for
      lung transplantation. Previous studies are limited by small numbers of patients
      with specific forms of diffuse lung disease. Children with all forms of diffuse
      lung disease who underwent lung transplantation at two pediatric centers were
      evaluated in terms of several pre- and post-transplant factors and compared to
      children with other end stage lung disorders. METHODS: A retrospective chart
      review was performed on all patients transplanted between October 1, 2002 and
      June 15, 2007 at Texas Children's Hospital and St. Louis Children's Hospital.
      Multiple pre-transplant characteristics and post-transplant morbidities and
      mortality were compared between diffuse lung disease, cystic fibrosis, and
      pulmonary vascular disease groups. RESULTS: There were 31 diffuse lung disease
      (DLD), 57 cystic fibrosis (CF), and 16 pulmonary vascular disease (PVD) patients
      included in our analysis. Patients with DLD had significantly higher pre
      transplant morbidity including lower percent predicted of forced expiratory
      volume in first second (P = 0.013) and more patients with pulmonary hypertension
      (P = 0.001) and hypercapnia (P = 0.031). Compared to CF patients, more DLD and
      PVD patients required invasive ventilation (P = 0.001) and care in the pediatric
      intensive care unit (P = 0.001). After transplant, there was a difference among
      the three groups with regards to number of acute allograft rejections but
      statistical limitations preclude knowing between which group the difference lies.
      A difference in time to bronchiolitis obliterans was found between the PVD and CF
      groups but not when compared to the DLD patients. The three groups had similar
      time to post-transplant lymphoproliferative disease, rate of infections, and
      survival. CONCLUSION: Lung transplantation is as successful for patients with end
      stage diffuse lung disease as compared to other lung transplant candidates.

PMID- 22949410
TI  - Schizonepeta tenuifolia inhibits the development of atopic dermatitis in mice.
AB  - Historically, Schizonepeta tenuifolia (ST) has been used for the treatment of
      skin disorders, such as allergic dermatitis, eczema, and inflammatory diseases.
      In this study, we examined whether ST inhibited 2,4-dinitrochlorobenzene (DNCB)
      induced atopic dermatitis (AD) in BALB/c mice. In histopathological analyses of
      the epidermis and dermis, skin thickness was significantly increased in DNCB
      induced mice as compared with normal group. Treatment with ST inhibited this
      inflammatory change and markedly suppressed the secretion of immunoglobulin E,
      tumor necrosis factor alpha, and interleukin 6 levels in the serum of DNCB
      induced mice. In addition, ST treatment significantly restored the upregulation
      of proinflammatory factors, such as nuclear factor (NF)-kappaB and mitogen
      activated protein kinase expression. Taken together, due to its ability to
      suppress inflammatory factors and upregulate proinflammatory factors, ST may be
      useful as a therapeutic treatment for AD. ST extract application decreased both
      epidermis and dermis thickness in DNCB-induced mice. In serum, ST reduced
      immunoglobulin E, tumor necrosis factor, and interleukin 6 level. In addition, ST
      suppressed NF-kappaB activation as well as the mitogen-activated protein kinase
      activities.

PMID- 22949411
TI  - Combination therapy with immune-modulators and moxifloxacin on fulminant
      macrolide-resistant Mycoplasma pneumoniae infection: A case report.
AB  - This report entails a case of refractory pneumonia with a wild variety of extra
      pulmonary manifestations due to macrolide-resistant Mycoplasma pneumoniae
      infection in a 7-year-old boy. The diagnosis was based on isolating M. pneumoniae
      through cultivation from the patient's bronchial aspirations at admission and the
      following susceptibility testing. Initial treatments consisting of a combination
      of azithromycin and standard-dosed methylprednisone (2 mg/kg) were completely
      nonresponsive and the patient's condition deteriorated rapidly. However,
      methylprednisone pulse therapy (20 mg/kg for 3 days, tapering within 1 month) and
      intravenous immunoglobulin (1 g/kg/day, two doses), in addition to moxifloxacin
      (10 mg/kg for 7 days) were remarkably effective and led to a favorable outcome
      without any observed side effects during inpatient hospitalization and outpatient
      follow-up.

PMID- 22949412
TI  - Proliferative and nonproliferative lesions of the rat and mouse male reproductive
      system.
AB  - The INHAND Project (International Harmonization of Nomenclature and Diagnostic
      Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of
      Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and
      North America (STP) to develop an internationally accepted nomenclature for
      proliferative and nonproliferative lesions in laboratory animals. The purpose of
      this publication is to provide a standardized nomenclature and differential
      diagnosis for classifying microscopic lesions observed in the male reproductive
      system of laboratory rats and mice, with color microphotographs illustrating
      examples of some lesions. The standardized nomenclature presented in this
      document is also available for society members electronically on the Internet
      (http://goreni.org). Sources of material included histopathology databases from
      government, academia, and industrial laboratories throughout the world. Content
      includes spontaneous and aging lesions as well as lesions induced by exposure to
      test materials. A widely accepted and utilized international harmonization of
      nomenclature for lesions of the male reproductive system in laboratory animals
      will decrease confusion among regulatory and scientific research organizations in
      different countries and provide a common language to increase and enrich
      international exchanges of information among toxicologists and pathologists.

PMID- 22949414
TI  - New reference equations to improve interpretation of infant lung function.
AB  - RATIONALE: With increasing use of infant pulmonary function tests (IPFTs) in both
      clinical and research studies, appropriate interpretation of results is
      essential. OBJECTIVES: To investigate the potential bias associated with
      "normalising" IPF by expressing results as a ratio of body size and to develop
      reference ranges for tidal breathing parameters, passive respiratory mechanics
      (compliance [Crs] and resistance [Rrs]) and plethysmographic functional residual
      capacity (FRCp ) for white infants during the first 2 years of life. METHODS:
      IPFTs were measured using the Jaeger BabyBody system and standardized protocols.
      Reference equations, adjusted for body size, age, and sex where appropriate, were
      created using multilevel modeling. RESULTS: The ratio of lung function to body
      length changes markedly with growth, thereby precluding its use for any outcome.
      While the ratio of tidal volume and Crs to body weight remained relatively
      constant with growth, this was not the case for FRCp . Even in healthy infants, a
      strong inverse relationship was observed between lung function/body weight and
      weight z-score which could distort interpretation of results in growth-restricted
      infants with lung disease, such as cystic fibrosis. Reference equations were
      derived from 153 healthy white infants on 232 test occasions (median age 35.5
      weeks [range: 2.6-104.7]). Crown-heel length was the strongest predictor of IPF.
      CONCLUSIONS: When reporting IPF, use of size-corrected ratios should be
      discouraged, with interpretation instead based on appropriate reference
      equations. The current equations are applicable to white infants and young
      children up to 2 years of age, studied using the same commercially available
      equipment. The extent to which these equations are applicable to infants and
      young children of other ethnic backgrounds or who are tested with different
      equipment needs to be established.

PMID- 22949413
TI  - Proliferative and nonproliferative lesions of the rat and mouse mammary,
      Zymbal's, preputial, and clitoral glands.
AB  - The mammary gland of laboratory rodents is an important organ for the evaluation
      of effects of xenobiotics, especially those that perturb hormonal homeostasis or
      are potentially carcinogenic. Mammary gland cancer is a leading cause of human
      mortality and morbidity worldwide and is a subject of major research efforts
      utilizing rodent models. Zymbal's, preputial, and clitoral glands are standard
      tissues that are evaluated in animal models that enable human risk assessment of
      xenobiotics. A widely accepted and utilized international harmonization of
      nomenclature for mammary, Zymbal's, preputial, and clitoral gland lesions in
      laboratory animals will improve diagnostic alignment among regulatory and
      scientific research organizations and enrich international exchanges of
      information among toxicologists and pathologists.

PMID- 22949415
TI  - Next steps for Vision and Change: moving from setting the vision to change.

PMID- 22949416
TI  - Integrating genomics research throughout the undergraduate curriculum: a
      collection of inquiry-based genomics lab modules.

PMID- 22949417
TI  - Common origins of diverse misconceptions: cognitive principles and the
      development of biology thinking.
AB  - Many ideas in the biological sciences seem especially difficult to understand,
      learn, and teach successfully. Our goal in this feature is to explore how these
      difficulties may stem not from the complexity or opacity of the concepts
      themselves, but from the fact that they may clash with informal, intuitive, and
      deeply held ways of understanding the world that have been studied for decades by
      psychologists. We give a brief overview of the field of developmental cognitive
      psychology. Then, in each of the following sections, we present a number of
      common challenges faced by students in the biological sciences. These may be in
      the form of misconceptions, biases, or simply concepts that are difficult to
      learn and teach, and they occur at all levels of biological analysis (molecular,
      cellular, organismal, population, and ecosystem). We then introduce the notion of
      a cognitive construal and discuss specific examples of how these cognitive
      principles may explain what makes some misconceptions so alluring and some
      biological concepts so challenging for undergraduates. We will argue that
      seemingly unrelated misconceptions may have common origins in a single underlying
      cognitive construal. These ideas emerge from our own ongoing cross-disciplinary
      conversation, and we think that expanding this conversation to include other
      biological scientists and educators, as well as other cognitive scientists, could
      have significant utility in improving biology teaching and learning.

PMID- 22949418
TI  - Teacher preparation: one key to unlocking the gate to STEM literacy.

PMID- 22949419
TI  - Recent research in science teaching and learning.

PMID- 22949420
TI  - Cell biology apps for Apple devices.
AB  - Apps for touch-pad devices hold promise for guiding and supporting learning.
      Students may use them in the classroom or on their own for didactic instruction,
      just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and
      iPhone) have a substantial share of the touch-pad device market (Campbell, 2012),
      this Feature will explore cell biology apps available from the App Store. My
      review includes iPad and iPhone apps available in June 2012, but does not include
      courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app
      on a five-point scale (1 star = lowest; 5 stars = highest) for educational and
      production values; I also provide an overall score.

PMID- 22949421
TI  - Moving beyond GK-12.
AB  - The National Science Foundation GK-12 program has made more than 300 awards to
      universities, supported thousands of graduate student trainees, and impacted
      thousands of K-12 students and teachers. The goals of the current study were to
      determine the number of sustained GK-12 programs that follow the original GK-12
      structure of placing graduate students into classrooms and to propose models for
      universities with current funding or universities interested in starting a
      program. Results from surveys, literature reviews, and Internet searches of
      programs funded between 1999 and 2008 indicated that 19 of 188 funded sites had
      sustained in-classroom programs. Three distinct models emerged from an analysis
      of these programs: a full-stipend model, in which graduate fellows worked with
      partner teachers in a K-12 classroom for 2 d/wk; a supplemental stipend model in
      which fellows worked with teachers for 1 d/wk; and a service-learning model, in
      which in-classroom activity was integrated into university academic coursework.
      Based on these results, potential models for sustainability and replication are
      suggested, including establishment of formal collaborations between sustained GK
      12 programs and universities interested in starting in-classroom programs;
      development of a new Teaching Experience for Fellows program; and integration of
      supplemental fellow stipends into grant broader-impact sections.

PMID- 22949422
TI  - Biology undergraduates' misconceptions about genetic drift.
AB  - This study explores biology undergraduates' misconceptions about genetic drift.
      We use qualitative and quantitative methods to describe students' definitions,
      identify common misconceptions, and examine differences before and after
      instruction on genetic drift. We identify and describe five overarching
      categories that include 16 distinct misconceptions about genetic drift. The
      accuracy of students' conceptions ranges considerably, from responses indicating
      only superficial, if any, knowledge of any aspect of evolution to responses
      indicating knowledge of genetic drift but confusion about the nuances of genetic
      drift. After instruction, a significantly greater number of responses indicate
      some knowledge of genetic drift (p = 0.005), but 74.6% of responses still contain
      at least one misconception. We conclude by presenting a framework that organizes
      how students' conceptions of genetic drift change with instruction. We also
      articulate three hypotheses regarding undergraduates' conceptions of evolution in
      general and genetic drift in particular. We propose that: 1) students begin with
      undeveloped conceptions of evolution that do not recognize different mechanisms
      of change; 2) students develop more complex, but still inaccurate, conceptual
      frameworks that reflect experience with vocabulary but still lack deep
      understanding; and 3) some new misconceptions about genetic drift emerge as
      students comprehend more about evolution.

PMID- 22949423
TI  - The benefits of multi-year research experiences: differences in novice and
      experienced students' reported gains from undergraduate research.
AB  - This mixed-methods study explores differences in novice and experienced
      undergraduate students' perceptions of their cognitive, personal, and
      professional gains from engaging in scientific research. The study was conducted
      in four different undergraduate research (UR) programs at two research-extensive
      universities; three of these programs had a focus on the biosciences. Seventy
      three entry-level and experienced student researchers participated in in-depth,
      semi-structured interviews and completed the quantitative Undergraduate Research
      Student Self-Assessment (URSSA) instrument. Interviews and surveys assessed
      students' developmental outcomes from engaging in UR. Experienced students
      reported distinct personal, professional, and cognitive outcomes relative to
      their novice peers, including a more sophisticated understanding of the process
      of scientific research. Students also described the trajectories by which they
      developed not only the intellectual skills necessary to advance in science, but
      also the behaviors and temperament necessary to be a scientist. The findings
      suggest that students benefit from multi-year UR experiences. Implications for UR
      program design, advising practices, and funding structures are discussed.

PMID- 22949424
TI  - Facilitating long-term changes in student approaches to learning science.
AB  - Undergraduates entering science curricula differ greatly in individual starting
      points and learning needs. The fast pace, high enrollment, and high stakes of
      introductory science courses, however, limit students' opportunities to self
      assess and modify learning strategies. The University of Washington's Biology
      Fellows Program (BFP) intervenes through a 20-session, premajors course that
      introduces students to the rigor expected of bioscience majors and assists their
      development as science learners. This study uses quantitative and qualitative
      approaches to assess whether the 2007-2009 BFP achieved its desired short- and
      long-term impacts on student learning. Adjusting for differences in students'
      high school grade point average and Scholastic Aptitude Test scores, we found
      that participation in the BFP was associated with higher grades in two subsequent
      gateway biology courses, across multiple quarters and instructors. Two to 4 yr
      after participating in the program, students attributed changes in how they
      approached learning science to BFP participation. They reported having learned to
      "think like a scientist" and to value active-learning strategies and learning
      communities. In addition, they reported having developed a sense of belonging in
      bioscience communities. The achievement of long-term impacts for a short-term
      instructional investment suggests a practical means to prepare diverse students
      for the rigors of science curricula.

PMID- 22949425
TI  - What are they thinking? Automated analysis of student writing about acid-base
      chemistry in introductory biology.
AB  - Students' writing can provide better insight into their thinking than can
      multiple-choice questions. However, resource constraints often prevent faculty
      from using writing assessments in large undergraduate science courses. We
      investigated the use of computer software to analyze student writing and to
      uncover student ideas about chemistry in an introductory biology course. Students
      were asked to predict acid-base behavior of biological functional groups and to
      explain their answers. Student explanations were rated by two independent raters.
      Responses were also analyzed using SPSS Text Analysis for Surveys and a custom
      library of science-related terms and lexical categories relevant to the
      assessment item. These analyses revealed conceptual connections made by students,
      student difficulties explaining these topics, and the heterogeneity of student
      ideas. We validated the lexical analysis by correlating student interviews with
      the lexical analysis. We used discriminant analysis to create classification
      functions that identified seven key lexical categories that predict expert
      scoring (interrater reliability with experts = 0.899). This study suggests that
      computerized lexical analysis may be useful for automatically categorizing large
      numbers of student open-ended responses. Lexical analysis provides instructors
      unique insights into student thinking and a whole-class perspective that are
      difficult to obtain from multiple-choice questions or reading individual
      responses.

PMID- 22949426
TI  - Multiple-choice exams: an obstacle for higher-level thinking in introductory
      science classes.
AB  - Learning science requires higher-level (critical) thinking skills that need to be
      practiced in science classes. This study tested the effect of exam format on
      critical-thinking skills. Multiple-choice (MC) testing is common in introductory
      science courses, and students in these classes tend to associate memorization
      with MC questions and may not see the need to modify their study strategies for
      critical thinking, because the MC exam format has not changed. To test the effect
      of exam format, I used two sections of an introductory biology class. One section
      was assessed with exams in the traditional MC format, the other section was
      assessed with both MC and constructed-response (CR) questions. The mixed exam
      format was correlated with significantly more cognitively active study behaviors
      and a significantly better performance on the cumulative final exam (after
      accounting for grade point average and gender). There was also less gender-bias
      in the CR answers. This suggests that the MC-only exam format indeed hinders
      critical thinking in introductory science classes. Introducing CR questions
      encouraged students to learn more and to be better critical thinkers and reduced
      gender bias. However, student resistance increased as students adjusted their
      perceptions of their own critical-thinking abilities.

PMID- 22949427
TI  - An educational intervention designed to increase women's leadership self
      efficacy.
AB  - Women are sparsely represented in leadership in academic science, technology,
      engineering, mathematics, and medicine (STEMM). Cultural stereotypes about men,
      women, and leaders influence the attitudes, judgments, and decisions that others
      make about women and the choices women make for themselves. Multilevel
      interventions are needed to counteract the impact of these pervasive and easily
      activated stereotypes, which conspire in multiple ways to constrain women's
      entry, persistence, and advancement in academic STEMM. We describe an individual
      level educational intervention. Using the transtheoretical model of behavioral
      change as a framework, we assessed the success of a semester course on increasing
      women's leadership self-efficacy for the first three cohorts of course
      participants (n = 30). Pre/post questionnaires showed gains in leadership self
      efficacy, personal mastery, and self-esteem, and decreases in perceived
      constraints. Qualitative text analysis of weekly journals indicated increasing
      leadership self-efficacy as course participants applied course information and
      integrated strategies to mitigate the impact of societal stereotypes into their
      own leadership practices. Follow-up queries of the first two cohorts supported
      the enduring value of course participation. We conclude that providing strategies
      to recognize and mitigate the impact of gender stereotypes is effective in
      increasing leadership self-efficacy in women at early stages of academic STEMM
      careers.

PMID- 22949428
TI  - Student learning outcomes and attitudes when biotechnology lab partners are of
      different academic levels.
AB  - The North Carolina State University Biotechnology Program offers laboratory
      intensive courses to both undergraduate and graduate students. In "Manipulation
      and Expression of Recombinant DNA," students are separated into undergraduate and
      graduate sections for the laboratory, but not the lecture, component. Evidence
      has shown that students prefer pairing with someone of the same academic level.
      However, retention of main ideas in peer learning environments has been shown to
      be greater when partners have dissimilar abilities. Therefore, we tested the
      hypothesis that there will be enhanced student learning when lab partners are of
      different academic levels. We found that learning outcomes were met by both
      levels of student, regardless of pairing. Average undergraduate grades on every
      assessment method increased when undergraduates were paired with graduate
      students. Many of the average graduate student grades also increased modestly
      when graduate students were paired with undergraduates. Attitudes toward working
      with partners dramatically shifted toward favoring working with students of
      different academic levels. This work suggests that offering dual-level courses in
      which different-level partnerships are created does not inhibit learning by
      students of different academic levels. This format is useful for institutions
      that wish to offer "boutique" courses in which student enrollment may be low, but
      specialized equipment and faculty expertise are needed.

PMID- 22949429
TI  - Phylogenetic and physicochemical analyses enhance the classification of rare
      nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome.
AB  - BACKGROUND: Hundreds of nonsynonymous single nucleotide variants (nsSNVs) have
      been identified in the 2 most common long-QT syndrome-susceptibility genes (KCNQ1
      and KCNH2). Unfortunately, an ~3% BACKGROUND: and KCNH2 nsSNVs amongst healthy
      individuals complicates the ability to distinguish rare pathogenic mutations from
      similarly rare yet presumably innocuous variants. METHODS AND RESULTS: In this
      study, 4 tools [(1) conservation across species, (2) Grantham values, (3) sorting
      intolerant from tolerant, and (4) polymorphism phenotyping] were used to predict
      pathogenic or benign status for nsSNVs identified across 388 clinically definite
      long-QT syndrome cases and 1344 ostensibly healthy controls. From these data,
      estimated predictive values were determined for each tool independently, in
      concert with previously published protein topology-derived estimated predictive
      values, and synergistically when >=3 tools were in agreement. Overall, all 4
      tools displayed a statistically significant ability to distinguish between case
      derived and control-derived nsSNVs in KCNQ1, whereas each tool, except Grantham
      values, displayed a similar ability to differentiate KCNH2 nsSNVs. Collectively,
      when at least 3 of the 4 tools agreed on the pathogenic status of C-terminal
      nsSNVs located outside the KCNH2/Kv11.1 cyclic nucleotide-binding domain, the
      topology-specific estimated predictive value improved from 56% to 91%.
      CONCLUSIONS: Although in silico prediction tools should not be used to predict
      independently the pathogenicity of a novel, rare nSNV, our results support the
      potential clinical use of the synergistic utility of these tools to enhance the
      classification of nsSNVs, particularly for Kv11.1's difficult to interpret C
      terminal region.

PMID- 22949430
TI  - Subtle abnormalities in contractile function are an early manifestation of
      sarcomere mutations in dilated cardiomyopathy.
AB  - BACKGROUND: Sarcomere mutations cause both dilated cardiomyopathy (DCM) and
      hypertrophic cardiomyopathy (HCM); however, the steps leading from mutation to
      disease are not well described. By studying mutation carriers before a clinical
      diagnosis develops, we characterize the early manifestations of sarcomere
      mutations in DCM and investigate how these manifestations differ from sarcomere
      mutations associated with HCM. METHODS AND RESULTS: Sixty-two genotyped
      individuals in families with sarcomeric DCM underwent clinical evaluation
      including strain echocardiography. The group included 12 subclinical DCM mutation
      carriers with normal cardiac dimensions and left ventricular ejection fraction
      (LVEF >=55%), 21 overt DCM subjects, and 29 related mutation (-) normal controls.
      Results were compared with a previously characterized cohort of 60 subclinical
      HCM subjects (sarcomere mutation carriers without left ventricular hypertrophy).
      Systolic myocardial tissue velocity, longitudinal, circumferential, and radial
      strain, and longitudinal and radial strain rate were reduced by 10%-23% in
      subclinical DCM mutation carriers compared with controls (P<0.001 for all
      comparisons), after adjusting for age and family relations. No significant
      differences in diastolic parameters were identified comparing the subclinical and
      control cohorts. The opposite pattern of contractile abnormalities with reduced
      diastolic but preserved systolic function was seen in subclinical HCM.
      CONCLUSIONS: Subtle abnormalities in systolic function are present in subclinical
      DCM mutation carriers, despite normal left ventricular size and ejection
      fraction. In contrast, impaired relaxation and preserved systolic function appear
      to be the predominant early manifestations of sarcomere mutations that lead to
      HCM. These findings support the theory that the mutation's intrinsic impact on
      sarcomere function influences whether a dilated or hypertrophic phenotype
      develops.

PMID- 22949431
TI  - Trastuzumab and congestive heart failure: what can we learn from use in the
      community?

PMID- 22949437
TI  - Payment reform: parlous, and yet still promising.

PMID- 22949432
TI  - Risk of heart failure in breast cancer patients after anthracycline and
      trastuzumab treatment: a retrospective cohort study.
AB  - BACKGROUND: Clinical trials demonstrated that women treated for breast cancer
      with anthracycline or trastuzumab are at increased risk for heart failure and/or
      cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We
      estimated real-world adjuvant anthracycline and trastuzumab use and their
      associations with incident HF/CM. METHODS: We conducted a population-based,
      retrospective cohort study of 12,500 women diagnosed with incident, invasive
      breast cancer from January 1, 1999 through December 31, 2007, at eight integrated
      Cancer Research Network health systems. Using administrative procedure and
      pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy
      use. We identified incident HF/CM following chemotherapy initiation and assessed
      risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy.
      Multivariable Cox proportional hazards regression models were used to estimate
      hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at
      diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation
      therapy, and comorbidities. RESULTS: Among 12 500 women (mean age = 60 years,
      range = 22-99 years), 29.6% received anthracycline alone, 0.9% received
      trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received
      other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and
      trastuzumab recipients were younger, with fewer comorbidities than recipients of
      other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was
      higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI =
      1.11 to 1.76), although the increased risk was similar to other chemotherapy
      (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in
      patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to
      7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to
      10.35). CONCLUSIONS: Anthracycline and trastuzumab were primarily used in
      younger, healthier women and associated with increased HF/CM risk compared with
      no chemotherapy. This population-based observational study complements findings
      from clinical trials on cancer treatment safety.

PMID- 22949438
TI  - The Food and Drug Administration gets new tools to spur regulatory science.

PMID- 22949439
TI  - The lessons of Medicare's prospective payment system show that the bundled
      payment program faces challenges.
AB  - Policy makers have been trying to replace Medicare's fee-for-service payment
      system for years with approaches that pay one price for an aggregation of
      services. The intent is to reward providers for offering needed care in the most
      appropriate and cost-effective manner. Medicare's first payment change designed
      to accomplish such a change was the hospital prospective payment system,
      introduced during 1983-84. But because it focused only on hospital care, its
      impact on total Medicare spending was limited. In 2011 Medicare began a new
      initiative to expand the "bundled payment" concept to link payments for multiple
      services that patients receive during an episode of care. The goal of Medicare's
      current bundled payment initiative is to provide incentives to deliver health
      care more efficiently while maintaining or improving quality. This article
      provides a detailed analysis of how Medicare implemented the hospital prospective
      payment system, how hospitals responded to the new incentives, and lessons
      learned that are applicable to the bundled payment initiative. The lessons
      include that any Medicare payment reform needs to continuously respond to the
      many different components of the health system and that payment reform should be
      coupled with analogous reforms in private insurance payment, so that providers
      receive consistent signals to alter their behavior.

PMID- 22949440
TI  - A giant of health policy reflects on past reforms.

PMID- 22949441
TI  - Medicare's new hospital value-based purchasing program is likely to have only a
      small impact on hospital payments.
AB  - Medicare's new hospital pay-for-performance program for all acute care hospitals
      will begin in October 2012. It will be the largest Medicare quality improvement
      initiative for hospitals to date. Using 2009 data on hospital performance, we
      calculated hospital performance scores and projected payments under the new
      program for all eligible hospitals. Despite differences across hospitals in terms
      of performance, expected changes in payments were small, even for hospitals with
      the best and worst performance scores. Almost two-thirds of hospitals would
      experience changes of just a fraction of 1 percent. Although the program will in
      effect redistribute resources among hospitals, our data suggest that the
      redistribution is not likely to cause major problems because the amount being
      redistributed is also small. These results raise questions about whether the new
      pay-for-performance program will substantially alter the quality of hospital
      care, and they highlight the challenges of designing effective quality
      improvement incentives.

PMID- 22949443
TI  - Beyond capitation: how new payment experiments seek to find the 'sweet spot' in
      amount of risk providers and payers bear.
AB  - A key issue in the decades-long struggle over US health care spending is how to
      distribute liability for expenses across all market participants, from insurers
      to providers. The rise and abandonment in the 1990s of capitation payments-lump
      sum, per person payments to health care providers to provide all care for a
      specified individual or group-offers a stark example of how difficult it is for
      providers to assume meaningful financial responsibility for patient care. This
      article chronicles the expansion and decline of the capitation model in the
      1990s. We offer lessons learned and assess the extent to which these lessons have
      been applied in the development of contemporary forms of provider cost sharing,
      particularly accountable care organizations, which in effect constitute a search
      for the "sweet spot," or appropriate place on a spectrum, between providers and
      payers with respect to the degree of risk they absorb.

PMID- 22949442
TI  - Medicare postacute care payment reforms have potential to improve efficiency of
      care, but may need changes to cut costs.
AB  - The Affordable Care Act mandates changes in payment policies for Medicare
      postacute care services intended to contain spending in the long run and help
      ensure the program's financial sustainability. In addition to reducing annual
      payment increases to providers under the existing prospective payment systems,
      the act calls for demonstration projects of bundled payment, accountable care
      organizations, and other strategies to promote care coordination and reduce
      spending. Experience with the adoption of Medicare prospective payment systems in
      postacute care settings approximately a decade ago suggests that current reforms
      could, but need not necessarily, produce such undesirable effects as decreased
      access for less profitable patients, poorer patient outcomes, and only short
      lived curbs on spending. Policy makers will need to be vigilant in monitoring the
      impact of the Affordable Care Act reforms and be prepared to amend policies as
      necessary to ensure that the reforms exert persistent controls on spending
      without compromising the delivery of patient-appropriate postacute services.

PMID- 22949444
TI  - The design and application of shared savings programs: lessons from early
      adopters.
AB  - Different forms of physician payment result in different levels of financial risk
      for health care payers and providers, and can affect clinical decision making and
      the cost of care. Shared savings programs reward providers for holding spending
      below specific targets, thus introducing a level of financial accountability not
      present in strictly volume-based payment models, such as fee-for-service. Here we
      examine the design and application of shared savings formulas across a range of
      actual programs. We also present a more detailed description of one particular
      shared savings program-the Massachusetts Patient-Centered Medical Home Initiative
      focusing on key trade-offs between payers and providers that eventually led to
      agreement on specific aspects of the program. We conclude with principles for the
      design of future shared savings arrangements and consideration of issues that
      will confront decision makers as these efforts mature and expand.

PMID- 22949445
TI  - A global budget pilot project among provider partners and Blue Shield of
      California led to savings in first two years.
AB  - Health care plans and providers in the private sector are developing alternative
      payment and delivery models to reduce spending and improve health care quality.
      To respond to intense competition from other organizations, Blue Shield of
      California created a partnership with health care providers to use an annual
      global budget for total expected spending and to share risk and savings among
      partners for providing health care. The patient population consisted of certain
      members of the California Public Employees' Retirement System in Northern
      California. Launched in 2010, the pilot accountable care organization in
      Sacramento provided a framework for operations and established goals and
      financial risk arrangements. The model shows early promise for its ease of
      implementation and effectiveness in controlling costs. During the two-year
      period, the total compound annual growth rate for per member per month cost was
      approximately 3 percent, or less than half the rate at which premiums rose over
      the past decade. Some of the savings stemmed from declines in inpatient lengths
      of-stay and thirty-day readmission rates. Results suggest that the approach can
      achieve considerable financial savings in as little as one year and can gain wide
      acceptance from reform-minded providers.

PMID- 22949446
TI  - Fee-for-service will remain a feature of major payment reforms, requiring more
      changes in Medicare physician payment.
AB  - Many health policy analysts envision provider payment reforms currently under
      development as replacements for the traditional fee-for-service payment system.
      Reforms include per episode bundled payment and elements of capitation, such as
      global payments or accountable care organizations. But even if these approaches
      succeed and are widely adopted, the core method of payment to many physicians for
      the services they provide is likely to remain fee-for-service. It is therefore
      critical to address the current shortcomings in the Medicare physician fee
      schedule, because it will affect physician incentives and will continue to play
      an important role in determining the payment amounts under payment reform. This
      article reviews how the current payment system developed and is applied, and it
      highlights areas that require careful review and modification to ensure the
      success of broader payment reform.

PMID- 22949447
TI  - Many large medical groups will need to acquire new skills and tools to be ready
      for payment reform.
AB  - Federal and state policy makers are now experimenting with programs that hold
      health systems accountable for delivering care under predetermined budgets to
      help control health care spending. To assess how well prepared medical groups are
      to participate in these arrangements, we surveyed twenty-one large,
      multispecialty groups. We evaluated their participation in risk contracts such as
      capitation and the degree of operational support associated with these
      arrangements. On average, about 25 percent of the surveyed groups' patient care
      revenue stemmed from global capitation contracts and 9 percent from partial
      capitation or shared risk contracts. Groups with a larger share of revenue from
      risk contracts were more likely than others to have salaried physicians, advanced
      data management capabilities, preferred relationships with efficient specialists,
      and formal programs to coordinate care for high-risk patients. Our findings
      suggest that medical groups that lack risk contracting experience may need to
      develop new competencies and infrastructure to successfully navigate federal
      payment reform programs, including information systems that track performance and
      support clinicians in delivering good care; physician-level reward systems that
      are aligned with organizational goals; sound physician leadership; and an
      organizational commitment to supporting performance improvement. The difficulty
      of implementing these changes in complex health care organizations should not be
      underestimated.

PMID- 22949448
TI  - Michigan's Physician Group Incentive Program offers a regional model for
      incremental 'fee for value' payment reform.
AB  - Blue Cross Blue Shield of Michigan partnered with providers across the state to
      create an innovative, "fee for value" physician incentive program that would
      deliver high-quality, efficient care. The Physician Group Incentive Program
      rewards physician organizations-formal groups of physicians and practices that
      can accept incentive payments on behalf of their members-based on the number of
      quality and utilization measures they adopt, such as generic drug dispensing
      rates, and on their performance on these measures across their patient
      populations. Physicians also receive payments for implementing a range of patient
      centered medical home capabilities, such as patient registries, and they receive
      higher fees for office visits for incorporating these capabilities into routine
      practice while also improving performance. Taken together, the incentive dollars,
      fee increases, and care management payments amount to a potential increase in
      reimbursement of 40 percent or more from Blue Cross Blue Shield of Michigan for
      practices designated as high-performing patient-centered medical homes. At the
      same time, we estimate that implementing the patient-centered medical home
      capabilities was associated with $155 million in lower medical costs in program
      year 2011 for Blue Cross Blue Shield of Michigan members. We intend to devote a
      higher percentage of reimbursement over time to communities of caregivers that
      offer high-value, system-based care, and a lower percentage of reimbursement to
      individual physicians on a service-specific basis.

PMID- 22949449
TI  - Early results show WellPoint's patient-centered medical home pilots have met some
      goals for costs, utilization, and quality.
AB  - Primary care must be reengineered to improve outcomes and affordability. To
      achieve those goals, WellPoint invested in ten patient-centered medical home
      pilots that encourage care coordination, preventive care, and shared decision
      making. Two of the three pilots described in this article-in Colorado and New
      Hampshire-layer incentive payments for care coordination and quality improvement
      on top of a traditional fee-for-service payment. The third-in New York-pays
      doctors an enhanced fee that is tied to achievement of quality levels.
      Preliminary evaluations show encouraging signs that the Colorado and New
      Hampshire pilots are meeting some cost, utilization, and quality objectives. A
      full evaluation in all three states is ongoing. To help enable systemwide
      transformation, WellPoint is now applying similar payment strategies to primary
      care practices that may not have the resources to become full-fledged medical
      homes.

PMID- 22949450
TI  - Colorado's Patient-Centered Medical Home Pilot met numerous obstacles, yet saw
      results such as reduced hospital admissions.
AB  - The Colorado Multipayer Patient-Centered Medical Home Pilot, which ran from May
      2009 through April 2012, was one of the first voluntary multipayer medical home
      pilot projects in the country. Six health plans, the state's high-risk pool
      carrier, and sixteen family or internal medicine practices with approximately
      100,000 patients participated. Although a full analysis is currently under way,
      preliminary results show that the pilot significantly reduced emergency
      department visits and also reduced hospital admissions, particularly for patients
      with multiple chronic conditions. One payer reported a return on its investment
      of 250-400 percent in the pilot. However, participants also ran into numerous
      obstacles. Among them: Many practices were left providing extra services to a
      large fraction of patients whose employer-sponsored insurance plans declined to
      pay the enhanced fees necessary to cover the cost of the patient-centered medical
      home expansion. The experience demonstrates that creating patient-centered
      medical homes and enabling them to be successful will take strong commitments and
      collaborative efforts on multiple fronts.

PMID- 22949451
TI  - Horizon's patient-centered medical home program shows practices need much more
      than payment changes to transform.
AB  - Skyrocketing costs and the uneven quality of patient care challenge the US health
      care system. Some health insurance companies are exploring patient-centered
      medical homes as a way to change incentives and transform the health care
      delivery system by increasing primary care providers' accountability for care
      coordination and outcomes. Horizon Healthcare Services, Inc., New Jersey's oldest
      and largest health insurance company, developed medical home programs that
      include financial incentives with essential support tools. Our experience in
      implementing and evaluating various approaches indicates that medical homes
      require intensive and targeted patient care coordination supported by committed
      primary care leadership, as well as new payment structures that include a monthly
      care coordination fee and outcome-based payments. Our experience also indicates
      that considerable nonmonetary support-such as an education program for population
      care coordinators, a medical home guide that offers effective ways to transform a
      practice into a medical home, and useful data sharing-are needed to improve the
      quality of care and reduce costs.

PMID- 22949452
TI  - Payers test reference pricing and centers of excellence to steer patients to low
      price and high-quality providers.
AB  - Hospitals frequently exhibit wide variation in their prices, and employers and
      insurers are now experimenting with the use of incentives to encourage employees
      to make price-conscious choices. This article examines two major new benefit
      design instruments being tested. In reference pricing, an employer or insurer
      makes a defined contribution toward covering the cost of a particular service and
      the patient pays the remainder. Through centers of excellence, employers or
      insurers limit coverage or strongly encourage patients to use particular
      hospitals for such procedures as orthopedic joint replacement, interventional
      cardiology, and cardiac surgery. We compare these two types of benefit designs
      with respect to consumer choice and how they balance price and quality. The
      article then examines their potential role in the policy debate over appropriate
      coverage and cost-sharing requirements.

PMID- 22949453
TI  - Large employers that have lived through transformation say payment reform alone
      won't cut costs and reengineer care.
AB  - As payment reform in health care gathers momentum, employers, as major payers,
      endorse the effort to move away from volume-driven payment to incentivizing and
      rewarding the delivery of better health care at lower cost. In this commentary we
      discuss large employers' perspectives on three particular challenges that payment
      reform alone, as important as it is, may not be sufficient to address: high
      health care prices, inefficient and complex systems, and an outdated work
      environment ill designed to meet the pressing goals of better health care at
      lower cost. We believe that policies that support health care organizations in
      redesigning work processes will be essential to reducing prices and simplifying
      interactions in care delivery. We also believe that health care organizations
      will need to redesign their compensation systems to align their employees' pay
      with improvements in performance. To that end, we describe the major
      transformation that IBM underwent in the 1990s to position itself to compete in a
      radically changed computer marketplace. We also offer several policy
      recommendations to support health care organizations in making the necessary
      changes.

PMID- 22949454
TI  - Posing a framework to guide government's role in payment and delivery system
      reform.
AB  - Innovative payment reform initiatives occur in both the public and private
      sector, but the optimal role in such reforms of the public sector, specifically
      the Centers for Medicare and Medicaid Services, is up for debate. In this article
      we examine recent experiences with public-private collaboration on payment and
      delivery reform and present a framework for determining the role of the
      government in spurring reform. We argue that as a purchaser, the government
      should consider the scale and maturity of private-sector activity in determining
      how to approach designing and implementing payment and delivery system reform.
      The government can further spur innovation by implementing payment reform for
      providers less ready to participate in it-such as smaller provider groups with
      limited organizational and technological capacity to implement reform-through
      identifying best practices related to attribution models and quality benchmarks
      and promoting dialogue with the private sector about the testing of new reform
      programs.

PMID- 22949455
TI  - Medicare's payment strategy for end-stage renal disease now embraces bundled
      payment and pay-for-performance to cut costs.
AB  - Since 1973 Medicare has provided health insurance coverage to all people who have
      been diagnosed with end-stage renal disease, or kidney failure. In this article
      we trace the history of payment policies in Medicare's dialysis program from 1973
      to 2011, while also providing some insight into the rationale for changes made
      over time. Initially, Medicare adopted a fee-for-service payment policy for
      dialysis care, using the same reimbursement standards employed in the broader
      Medicare program. However, driven by rapid spending growth in this population,
      the dialysis program has implemented innovative payment reforms, such as
      prospective bundled payments and pay-for-performance incentives. It is uncertain
      whether these strategies can stem the increase in the total cost of dialysis to
      Medicare, or whether they can do so without adversely affecting the quality of
      care. Future research on the intended and unintended consequences of payment
      reform will be critical.

PMID- 22949456
TI  - Providers' payment and delivery system reforms hold both threats and
      opportunities for the drug and device industries.
AB  - For decades, medical device and specialty drug makers have produced a steady
      stream of breakthroughs and incremental improvements, from cancer therapies to
      orthopedic joint replacements, drug-eluting stents, and cardiac pacemakers. The
      advances were financed by a fragmented health care system that paid for whichever
      clinical technologies were favored by physicians without strong concern for cost.
      But now hospitals, health systems, insurers, and policy makers are embracing
      payment reforms that seek to control costs and foster uniformity in the adoption
      of new drugs and devices. This article explores payment reforms that will have an
      impact on the medical technology industry and describes opportunities for the
      industry to flourish in this new, more financially constrained landscape.

PMID- 22949457
TI  - How Geisinger structures its physicians' compensation to support improvements in
      quality, efficiency, and volume.
AB  - The movement of US physicians toward working as employees rather than working as
      private practitioners is increasing interest in compensation systems that drive
      improved quality and efficiency without compromising the productivity of existing
      fee-for-service payment systems. We describe the approach of Geisinger Health
      System, an integrated delivery system in Pennsylvania that assigns about 20
      percent of total expected physician compensation to incentives that support
      improvements in quality and efficiency along with growth in clinical volume. We
      believe that dedicating a moderate portion of physician compensation to achieving
      strategic goals, such as maximizing quality and efficiency, is improving the
      value of care provided at Geisinger. At the same time, because most of
      Geisinger's clinical care is still delivered and paid for on a fee-for-service
      basis, the incentives for clinical volume are enabling Geisinger to achieve the
      financial viability to pursue its mission.

PMID- 22949458
TI  - Payer-provider collaboration in accountable care reduced use and improved quality
      in Maine Medicare Advantage plan.
AB  - Patient-centered, accountable care has garnered increased attention with the
      passage of the Affordable Care Act and new Medicare regulations. This case study
      examines a care model jointly developed by a provider and a payer that
      approximates an accountable care organization for a Medicare Advantage
      population. The collaboration between Aetna and NovaHealth, an independent
      physician association based in Portland, Maine, focused on shared data, financial
      incentives, and care management to improve health outcomes for approximately 750
      Medicare Advantage members. The patient population in the pilot program had 50
      percent fewer hospital days per 1,000 patients, 45 percent fewer admissions, and
      56 percent fewer readmissions than statewide unmanaged Medicare populations.
      NovaHealth's total per member per month costs across all cost categories for its
      Aetna Medicare Advantage members were 16.5 percent to 33 percent lower than costs
      for members not in this provider organization. Clinical quality metrics for
      diabetes, ischemic vascular disease, annual office visits, and postdischarge
      follow-up for patients in the program were consistently high. The experience of
      developing and implementing this collaborative care model suggests that several
      components are key, including robust data sharing and information systems that
      support it, analytical support, care management and coordination, and joint
      strategic planning with close provider-payer collaboration.

PMID- 22949459
TI  - Wide variation in episode costs within a commercially insured population
      highlights potential to improve the efficiency of care.
AB  - Reforming payment methods to move away from fee-for-service reimbursement is
      widely seen as a crucial step toward controlling health care costs. Although
      there is a good deal of evidence about variability in costs under Medicare,
      little has been published about the variability of costs for care that is
      financed by private insurance. We examined both quality and actual medical costs
      for episodes of care provided by nearly 250,000 US physicians serving
      commercially insured patients nationwide. Overall, episode costs for a set of
      major medical procedures varied about 2.5-fold, and for a selected set of common
      chronic conditions, episode costs varied about 15-fold. Among doctors meeting
      quality and efficiency benchmarks, however, costs for episodes of care were on
      average 14 percent lower than among other doctors. Some markets exhibited much
      higher variation in episode costs, but there was essentially no correlation
      between average episode costs and measured quality across markets. The overall
      analysis suggests that changing incentives through payment reforms could help to
      improve performance, but providers are at different stages of readiness for such
      reforms and thus will often need support in order to succeed.

PMID- 22949460
TI  - Introducing decision aids at Group Health was linked to sharply lower hip and
      knee surgery rates and costs.
AB  - Decision aids are evidence-based sources of health information that can help
      patients make informed treatment decisions. However, little is known about how
      decision aids affect health care use when they are implemented outside of
      randomized controlled clinical trials. We conducted an observational study to
      examine the associations between introducing decision aids for hip and knee
      osteoarthritis and rates of joint replacement surgery and costs in a large health
      system in Washington State. Consistent with prior randomized trials, our
      introduction of decision aids was associated with 26 percent fewer hip
      replacement surgeries, 38 percent fewer knee replacements, and 12-21 percent
      lower costs over six months. These findings support the concept that patient
      decision aids for some health conditions, for which treatment decisions are
      highly sensitive to both patients' and physicians' preferences, may reduce rates
      of elective surgery and lower costs.

PMID- 22949461
TI  - Personal responsibility: how Mitt Romney embraced the individual mandate in
      Massachusetts health reform.

PMID- 22949462
TI  - How I helped create a flawed mental health system that's failed millions--and my
      son.

PMID- 22949465
TI  - A randomized trial of 'hospital at home'.

PMID- 22949467
TI  - Caring for those eligible for Medicaid and Medicare.

PMID- 22949468
TI  - The 'knotty' problem of dual eligibles.

PMID- 22949469
TI  - Physicians can help unhealthy communities.

PMID- 22949470
TI  - Silent stroke: not listened to rather than silent.
AB  - BACKGROUND AND PURPOSE: The prevalence of silent brain infarcts varies from 8% to
      28% in the general elderly population. Silent brain infarcts are associated with
      increased risk of subsequent stroke and cognitive dysfunction. By definition,
      silent strokes lack clinically overt stroke-like symptoms and fail to come to
      clinical attention; however, impaired recall of symptoms may be a potential
      confounder. Our aim is to report a series of patients with incidentally detected
      acute and subacute strokes and examine whether they were truly asymptomatic.
      METHODS: Subjects included in this study were drawn from ongoing dementia
      research studies at the Memory Ageing and Cognition Center, in which all
      participants underwent a cranial MRI. Incidental hyperintense lesions on
      diffusion-weighted imaging with corresponding apparent diffusion coefficient
      defects indicative of acute/subacute silent stroke were identified. Clinical data
      for individuals with incidental hyperintense lesions on diffusion-weighted
      imaging were collated. RESULTS: Six of 649 subjects had incidental hyperintense
      lesions on diffusion-weighted imaging; on retrospective questioning, 3 recalled
      symptoms temporally correlated with MRI lesions, which had been reported to but
      ignored by family members. Two subjects had focal neurological signs. A majority
      of the subjects with incidental hyperintense lesions on diffusion-weighted
      imaging had significant cognitive impairment. CONCLUSIONS: A significant number
      of strokes may be "silent" due to lack of awareness of stroke-like symptoms in
      the elderly and their families. Enhanced stroke prevention education strategies
      are needed for the elderly population and, in particular, for their families.

PMID- 22949471
TI  - Effect of focal ischemia on long noncoding RNAs.
AB  - BACKGROUND AND PURPOSE: Long noncoding RNAs (lncRNAs) play a significant role in
      cellular physiology. We evaluated the effect of focal ischemia on the expression
      of 8314 lncRNAs in rat cerebral cortex using microarrays. METHODS: Ischemia was
      induced by transient middle cerebral artery occlusion. Genomic and transcriptomic
      correlates of the stroke-responsive lncRNAs and the transcription factor binding
      sties in their promoters were evaluated with bioinformatics. RESULTS: Three
      hundred fifty-nine lncRNAs were upregulated (>2-fold) and 84 were downregulated
      (<0.5-fold) at 3 hours to 12 hours of reperfusion after middle cerebral artery
      occlusion compared with sham. Sixty-two stroke-responsive lncRNAs showed >90%
      sequence homology with exons of protein-coding genes. Promoters of stroke
      responsive lncRNA genes and their homologous protein-coding genes showed highly
      overlapping transcription factor binding sites. Despite presence of open reading
      frames, lncRNAs did not form any product when subjected to in vitro translation.
      CONCLUSIONS: Stroke significantly alters cerebral lncRNA expression profiles.

PMID- 22949472
TI  - Different impacts of blood pressure variability on the progression of cerebral
      microbleeds and white matter lesions.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) and white matter lesions (WML)
      are cerebral small vessel diseases. Hypertension is considered the most important
      risk factor. Its mechanism is not yet clarified. Our study assessed the
      association of blood pressure variability (BPV) with CMB and WML progression.
      METHODS: Patients with a history of ischemic stroke within 1 to 6 months were
      consecutively recruited and followed-up for 12 to 18 months. Blood pressure was
      measured monthly and controlled to a target level. BPV was quantified by the
      maximum, standard deviation, coefficient of variation, successive variation,
      standard deviation independent of mean, and successive variation independent of
      mean. Magnetic resonance imaging was performed at baseline and the end of the
      study. CMB and WML were rated using Microbleed Anatomic Rating Scale and Age
      Related White Matter Changes scales, respectively. Multiple logistic analyses
      assessed BPV associations with CMB and WML development. RESULTS: Of 720 patients
      recruited, 500 and 584 had follow-up results for CMB and WML, respectively; 13.2%
      and 48.1% showed CMB and WML progression, respectively, over a median of 14
      months. Patients with CMB had a higher mean, maximum, standard deviation,
      coefficient of variation, successive variation, standard deviation independent of
      the mean, and successive variation independent of the mean in either systolic
      blood pressure or diastolic blood pressure (P<0.05). Systolic blood pressure
      variability was an independent risk factor for deep and infratentorial CMB
      progression, whereas diastolic blood pressure variability was independently
      associated with CMB development in deep regions. WML progression was not
      significantly associated with BPV between visits. CONCLUSIONS: BPV independently
      predicts CMB progression in deep and infratentorial regions. CLINICAL TRIAL
      REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00202020.

PMID- 22949473
TI  - How are household economic circumstances affected after a stroke? The
      Psychosocial Outcomes In StrokE (POISE) Study.
AB  - BACKGROUND AND PURPOSE: Stroke is associated with severe economic consequences.
      This is the first study to investigate in younger survivors the household
      economic burden of stroke. METHODS: A multicenter, 3-year prospective cohort
      study was conducted of younger (18-65 years) survivors in Australia. Pre- and
      poststroke patterns of income and hardship were evaluated and multivariable
      logistic regression identified the predictors of economic hardship after stroke.
      RESULTS: Four hundred fourteen participants were followed up over 12 months after
      stroke. The variables that independently predicted economic hardship after stroke
      were: female (OR, 2.94; 95% CI, 1.52-5.70), hazardous alcohol consumption (OR,
      2.28; 95% CI, 1.00-5.20), manual occupation (OR, 1.88; 95% CI, 1.07-3.30), lack
      of health insurance (OR, 2.01; 95% CI, 1.12-3.60), and prior hardship (OR, 3.93;
      95% CI, 2.12-7.29), whereas concessional status (OR, 0.50; 95% CI, 0.26-0.95) and
      more social contacts per week (OR, 0.99; 95% CI, 0.98-1.00) reduced hardship
      likelihood. CONCLUSIONS: Higher prestroke income did not buffer hardship after
      stroke nor did clinical, health service, or disability factors. Policies to
      reduce inequalities after stroke would be best aimed at socioeconomic targets.

PMID- 22949474
TI  - What is certain when the stroke etiology is uncertain?

PMID- 22949475
TI  - Transcranial Doppler ultrasound for screening cerebral small vessel disease: a
      community study.
AB  - BACKGROUND AND PURPOSE: We explored the association between pulsatility index
      (PI) as derived from transcranial Doppler ultrasound with various measures of
      small vessel disease in the community. METHODS: We performed transcranial Doppler
      and magnetic resonance imaging in 205 consecutive community-dwelling elderly
      subjects who were participants of the Shanghai Aging Study. We investigated the
      association between middle cerebral artery (MCA) PI with measures of white matter
      lesions (WML), lacunes, and microbleeds. RESULTS: Multiple logistic regression
      found that MCA PI was associated with severe WML (odds ratio, 1.33 per 0.1
      increase in PI; 95% confidence interval, 1.04-1.70; P=0.02). At optimal MCA PI
      cut-off, the area under curve, positive predictive value, and negative predictive
      value were 0.70 (95% confidence interval, 0.60-0.80), 34.9%, and 85.6%,
      respectively, for detection of severe WML. No association was found between MCA
      PI and measures of lacunes or microbleeds. CONCLUSIONS: PI correlates with WML
      severity. With a high negative predictive value, the chance of having severe WML
      with a normal PI is low. Transcranial Doppler may guide selective magnetic
      resonance imaging scanning for the detection of WML in the community.

PMID- 22949476
TI  - Arterial stiffness and progressive neurological deficit in patients with acute
      deep subcortical infarction.
AB  - BACKGROUND AND PURPOSE: The mechanism of progressive neurological deficit (PND)
      in patients with ischemic stroke remains unclear. The aim of this study was to
      clarify whether arterial stiffness, a marker of vascular endothelial impairment
      and arteriosclerosis, is associated with PND in patients with acute deep
      subcortical infarction. METHODS: We evaluated 156 consecutive first-ever ischemic
      stroke patients with acute deep subcortical infarction. PND was defined as an
      increment of >=2 points in the National Institute of Health Stroke Scale score or
      an increase of >=1 point in the limb weakness score within 7 days of stroke
      onset. Patients were assessed for risk factors, and infarct size was measured on
      initial diffusion-weighted magnetic resonance imaging. We measured brachial-ankle
      pulse wave velocity (baPWV) as a marker of arterial stiffness. We divided
      patients into 2 groups according to the presence or absence of PND to compare
      their clinical characteristics. RESULTS: Fifty-two patients (33%) had PND, and
      baPWV was significantly higher in patients with than in those without PND. The
      baPWV cut-off value for PND was 18.24 m/s, with 90% sensitivity and 47%
      specificity. In multivariable logistic regression analysis, high baPWV (>=18.24
      m/s; odds ratio, 8.22; 95% confidence interval, 2.55-31.9), large infarct size
      (>=15 mm; odds ratio, 2.76; 95% confidence interval, 1.01-7.92), and >=3 infarct
      slices on serial axial diffusion-weighted imaging (odds ratio, 3.38; 95%
      confidence interval, 1.22-10.0) were independently associated with PND.
      CONCLUSIONS: Arterial stiffness indicated by baPWV is independently associated
      with PND in patients with acute deep subcortical infarction.

PMID- 22949477
TI  - Inhaled nitric oxide reduces brain damage by collateral recruitment in a neonatal
      stroke model.
AB  - BACKGROUND AND PURPOSE: We recently demonstrated that endogenous nitric oxide
      (NO) modulates collateral blood flow in a neonatal stroke model in rats. The
      inhalation of NO (iNO) has been found to be neuroprotective after ischemic brain
      damage in adults. Our objective was to examine whether iNO could modify cerebral
      blood flow during ischemia-reperfusion and reduce lesions in the developing
      brain. METHODS: In vivo variations in cortical NO concentrations occurring after
      20-ppm iNO exposure were analyzed using the voltammetric method in P7 rat pups.
      Inhaled NO-mediated blood flow velocities were measured by ultrasound imaging
      with sequential Doppler recordings in both internal carotid arteries and the
      basilar trunk under basal conditions and in a neonatal model of ischemia
      reperfusion. The hemodynamic effects of iNO (5 to 80 ppm) were correlated with
      brain injury 48 hours after reperfusion. RESULTS: Inhaled NO (20 ppm)
      significantly increased NO concentrations in the P7 rat cortex and compensated
      for the blockade of endogenous NO synthesis under normal conditions. Inhaled NO
      (20 ppm) during ischemia increased blood flow velocities and significantly
      reduced lesion volumes by 43% and cellular damage. In contrast, both 80 ppm iNO
      given during ischemia and 5 or 20 ppm iNO given 30 minutes after reperfusion were
      detrimental. CONCLUSIONS: Our findings strongly indicate that, with the
      appropriate timing, 20 ppm iNO can be transported into the P7 rat brain and
      mediated blood flow redistribution during ischemia leading to reduced infarct
      volume and cell injury.

PMID- 22949478
TI  - Utility of Framingham Coronary Heart Disease Risk Score for predicting cardiac
      risk after stroke.
AB  - BACKGROUND AND PURPOSE: Coronary heart disease (CHD) is a major cause of
      mortality among stroke patients after the acute period. Simple risk
      stratification of stroke patients without known CHD may permit prompt
      implementation of CHD-specific management strategies for those who are at high
      risk for cardiac events. We assessed the utility of the Framingham Coronary Heart
      Disease Risk Score (FCRS) as a prognosticator in stroke patients without known
      CHD. METHODS: Post hoc analysis of a trial dataset of 3509 recent ischemic stroke
      patients who were aged 35 years or older, recruited from 56 centers, and followed
      up for 2 years. Patients were categorized as having known CHD, high FCRS (>=20%),
      and low/intermediate FCRS (<20%). The predictive values between baseline FCRS and
      primary (myocardial infarction [MI]), secondary (MI or vascular death), and
      tertiary (recurrent stroke) outcomes were assessed in multivariate analyses.
      RESULTS: Rates of first MI at 2 years were 6.34%, 4.65%, and 1.44% for the known
      CHD, high FCRS, and low/intermediate FCRS groups. Compared with stroke patients
      with low/intermediate FCRS, individuals with high FCRS had a higher risk of MI
      (adjusted hazard ratio, 3.70; 95% confidence interval, 2.14-6.38) and MI or
      vascular death (adjusted hazard ratio, 2.21; 95% confidence interval, 1.48-3.28).
      High FCRS did not predict recurrent stroke. CONCLUSIONS: Among patients with a
      recent ischemic stroke without known CHD, high FCRS was associated with a higher
      risk of MI and vascular death, but not stroke. FCRS could be a simple way to
      identify recent stroke patients who may benefit from additional CHD-specific
      management.

PMID- 22949479
TI  - Letter by Gomez-Choco and Garcia regarding article "spectrum of transient focal
      neurological episodes in cerebral amyloid angiopathy".

PMID- 22949480
TI  - Using biomarkers to disentangle different causes of Parkinsonism.

PMID- 22949481
TI  - Improving behavioral performance under full attention by adjusting response
      criteria to changes in stimulus predictability.
AB  - One of the key features of active perception is the ability to predict critical
      sensory events. Humans and animals can implicitly learn statistical regularities
      in the timing of events and use them to improve behavioral performance. Here, we
      used a signal detection approach to investigate whether such improvements in
      performance result from changes of perceptual sensitivity or rather from
      adjustments of a response criterion. In a regular sequence of briefly presented
      stimuli, human observers performed a noise-limited motion detection task by
      monitoring the stimulus stream for the appearance of a designated target
      direction. We manipulated target predictability through the hazard rate, which
      specifies the likelihood that a target is about to occur, given it has not
      occurred so far. Analyses of response accuracy revealed that improvements in
      performance could be accounted for by adjustments of the response criterion; a
      growing hazard rate was paralleled by an increasing tendency to report the
      presence of a target. In contrast, the hazard rate did not affect perceptual
      sensitivity. Consistent with previous research, we also found that reaction time
      decreases as the hazard rate grows. A simple rise-to-threshold model could well
      describe this decrease and attribute predictability effects to threshold
      adjustments rather than changes in information supply. We conclude that, even
      under conditions of full attention and constant perceptual sensitivity,
      behavioral performance can be optimized by dynamically adjusting the response
      criterion to meet ongoing changes in the likelihood of a target.

PMID- 22949482
TI  - Problems with estimation of ancestral frequencies under stationary models.

PMID- 22949483
TI  - Phylogenomic insights into the cambrian explosion, the colonization of land and
      the evolution of flight in arthropoda.
AB  - The timing of the origin of arthropods in relation to the Cambrian explosion is
      still controversial, as are the timing of other arthropod macroevolutionary
      events such as the colonization of land and the evolution of flight. Here we
      assess the power of a phylogenomic approach to shed light on these major events
      in the evolutionary history of life on earth. Analyzing a large phylogenomic
      dataset (122 taxa, 62 genes) with a Bayesian-relaxed molecular clock, we
      simultaneously reconstructed the phylogenetic relationships and the absolute
      times of divergences among the arthropods. Simulations were used to test whether
      our analysis could distinguish between alternative Cambrian explosion scenarios
      with increasing levels of autocorrelated rate variation. Our analyses support
      previous phylogenomic hypotheses and simulations indicate a Precambrian origin of
      the arthropods. Our results provide insights into the 3 independent colonizations
      of land by arthropods and suggest that evolution of insect wings happened much
      earlier than the fossil record indicates, with flight evolving during a period of
      increasing oxygen levels and impressively large forests. These and other findings
      provide a foundation for macroevolutionary and comparative genomic study of
      Arthropoda.

PMID- 22949484
TI  - TreeFix: statistically informed gene tree error correction using species trees.
AB  - Accurate gene tree reconstruction is a fundamental problem in phylogenetics, with
      many important applications. However, sequence data alone often lack enough
      information to confidently support one gene tree topology over many competing
      alternatives. Here, we present a novel framework for combining sequence data and
      species tree information, and we describe an implementation of this framework in
      TreeFix, a new phylogenetic program for improving gene tree reconstructions.
      Given a gene tree (preferably computed using a maximum-likelihood phylogenetic
      program), TreeFix finds a "statistically equivalent" gene tree that minimizes a
      species tree-based cost function. We have applied TreeFix to 2 clades of 12
      Drosophila and 16 fungal genomes, as well as to simulated phylogenies and show
      that it dramatically improves reconstructions compared with current state-of-the
      art programs. Given its accuracy, speed, and simplicity, TreeFix should be
      applicable to a wide range of analyses and have many important implications for
      future investigations of gene evolution. The source code and a sample data set
      are available at http://compbio.mit.edu/treefix.

PMID- 22949485
TI  - Response to 'Calcium, phosphate and the risk of cardiovascular events and all
      cause mortality in a population with stable coronary heart disease'.

PMID- 22949486
TI  - Problems with epidemiological approach and conclusions.

PMID- 22949487
TI  - Two zotarolimus-eluting stent generations: a meta-analysis of 12 randomised
      trials versus other limus-eluting stents and an adjusted indirect comparison.
AB  - OBJECTIVE: To evaluate efficacy and safety of two zotarolimus-eluting stent
      generations versus other limus-eluting stents (LES), and to compare Resolute
      zotarolimus-eluting stents (R-ZES) with Endeavor zotarolimus-eluting stents (E
      ZES). BACKGROUND: The performance of zotarolimus-eluting stents versus other LES,
      and the possible improvements of R-ZES versus E-ZES still remain to be defined.
      METHODS: We undertook a meta-analysis of trials in which patients were randomly
      assigned to percutaneous coronary interventions (PCI) with R-ZES versus LES, or
      with E-ZES versus LES, as well as an indirect comparison of R-ZES versus E-ZES,
      with LES as common comparator. The primary efficacy endpoint was ischaemia-driven
      target vessel revascularisation (ID-TVR); the primary safety endpoints were
      myocardial infarction (MI), cardiac death and cumulative definite/probable stent
      thrombosis (ST). RESULTS: Overall, 13'709 patients were assigned to PCI with R
      ZES versus LES (n=7185) or with E-ZES versus LES (n=6524). The risk of ID-TVR (OR
      (95% CI)=1.06 (0.90 to 1.25), p=0.47), MI (1.00 (0.81 to 1.25), p=0.97), cardiac
      death (0.99 (0.69 to 1.42), p=0.96) and ST (1.18 (0.68 to 2.03), p=0.56) did not
      differ between R-ZES and LES. Patients receiving E-ZES were more likely to
      undergo ID-TVR as compared with those receiving LES (1.95 (1.40 to 2.73),
      p<0.0001). The risk of MI (0.91 (0.54 to 1.54), p=0.73), cardiac death (1.02
      (0.54 to 1.91), p=0.96) and ST (1.10 (0.50 to 2.44), p=0.81) was similar between
      E-ZES and LES. At indirect comparison, PCI with R-ZES versus E-ZES reduced the
      risk of ID-TVR (0.54 (0.37 to 0.78), p=0.001), without increasing MI (1.09 (0.62
      to 1.93), p=0.74), cardiac death (0.97 (0.46 to 2.00), p=0.93) and ST (1.07 (0.40
      to 2.80), p=0.88). CONCLUSIONS: The antirestenotic efficacy of Resolute
      zotarolimus-eluting stents is superior to Endeavor zotarolimus-eluting stents and
      similar to other limus-eluting stents. Endeavor zotarolimus-eluting stents
      increase the risk of reinterventions as compared with other limus-eluting stents.
      First and second-generation zotarolimus-eluting stents have similar
      thrombogenicity compared with other limus-eluting stents.

PMID- 22949488
TI  - Predicting peri-procedural myocardial infarction during PCI.

PMID- 22949489
TI  - Hospital variation in readmission after coronary artery bypass surgery in
      California.
AB  - BACKGROUND: Readmissions are common after coronary artery bypass grafting (CABG)
      surgery and account for a significant percentage of hospital healthcare costs.
      Readmission rates also vary widely between hospitals, but the reasons for this
      variation have not been studied previously. METHODS AND RESULTS: We linked 2009
      California CABG clinical registry data to hospital discharge data for 2009 and
      2010 to identify 30-day readmissions for all patients undergoing isolated CABG
      surgery. Both standard and hierarchical logistic models were developed to predict
      readmission risk and explore sources of hospital readmission variation. Among 11
      823 patients discharged alive after isolated CABG in 2009, 1565 (13.2%) patients
      were readmitted within 30 days of surgery. Heart failure and postoperative
      infections were the most frequent reasons for readmission (15.3% and 12.9%,
      respectively). Multiple patient risk factors, including age, sex, and lower zip
      code-level median household income, were significant predictors of readmission
      (all adjusted odds ratios >1.0; P<0.05). The readmission rates among the 119
      hospitals performing CABG varied from 0% to 26.9%. Compared with hospitals in
      lower quartiles for readmission, hospitals in higher quartiles had a
      significantly higher readmission rates due to circulatory diseases, infections,
      complications for surgical and medical care and digestive diseases (all P<0.05).
      In a hierarchical model, including several hospital characteristics, hospital
      level variables did not predict readmission risk (all P>0.05, with an intraclass
      correlation of 0.004 for hospitals). CONCLUSIONS: California hospitals performing
      CABG surgery vary widely in 30-day readmission rates. Patient demographic and
      clinical risk factors, rather than measured hospital characteristics, accounted
      for most of the observed hospital-level variation in CABG readmissions.

PMID- 22949490
TI  - National trends in oral anticoagulant use in the United States, 2007 to 2011.
AB  - BACKGROUND: Little is known regarding the adoption of direct thrombin inhibitors
      in clinical practice. We examine trends in oral anticoagulation for the
      prevention of thromboembolism in the United States. METHODS AND RESULTS: We used
      the IMS Health National Disease and Therapeutic Index, a nationally
      representative audit of office-based providers, to quantify patterns of oral
      anticoagulant use among all subjects and stratified by clinical indication. We
      quantified oral anticoagulant expenditures using the IMS Health National
      Prescription Audit. Between 2007 and 2011, warfarin treatment visits declined
      from ~2.1 million (M) quarterly visits to ~1.6M visits. Dabigatran use increased
      from 0.062M quarterly visits (2010Q4) to 0.363M visits (2011Q4), reflecting its
      increasing share of oral anticoagulant visits from 3.1% to 18.9%. In contrast to
      warfarin, the majority of dabigatran visits have been for atrial fibrillation,
      though this proportion decreased from 92% (2010Q4) to 63% (2011Q4), with
      concomitant increases in dabigatran's off-label use. Among atrial fibrillation
      visits, warfarin use decreased from 55.8% visits (2010Q4) to 44.4% (2011Q4),
      whereas dabigatran use increased from 4.0% to 16.9%. Of atrial fibrillation
      visits, the fraction not treated with any oral anticoagulants has remained
      unchanged at ~40%. Expenditures related to dabigatran increased rapidly from $16M
      in 2010Q4 to $166M in 2011Q4, exceeding expenditures on warfarin ($144M) in
      2011Q4. CONCLUSIONS: Dabigatran has been rapidly adopted into ambulatory practice
      in the United States, primarily for treatment of atrial fibrillation, but
      increasingly for off-label indications. We did not find evidence that it has
      increased overall atrial fibrillation treatment rates.

PMID- 22949491
TI  - Development of 2 registry-based risk models suitable for characterizing hospital
      performance on 30-day all-cause mortality rates among patients undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: Variation in outcomes after percutaneous coronary interventions (PCI)
      may reflect differences in quality of care. To date, however, we lack a
      methodology to monitor and improve national hospital 30-day mortality rates among
      patients undergoing PCI. METHODS AND RESULTS: We developed hierarchical logistic
      regression models to calculate hospital risk-standardized 30-day all-cause PCI
      mortality rates. Due to differences in risk, patients were divided into 2
      cohorts: those with ST-segment elevation myocardial infarction or cardiogenic
      shock, and those with no ST-segment elevation myocardial infarction and no
      cardiogenic shock. The models were derived using 2006 data from the CathPCI
      Registry linked with administrative claims data, and validated using comparable
      2005 data. In the derivation cohort of the ST-segment elevation myocardial
      infarction or shock model (n=15 123), the unadjusted 30-day mortality rate was
      9.2%. The final model included 13 variables with the observed mortality rates
      ranging from 1.4% to 40.3% across deciles of the predicted patient mortality
      rates. The 25th and 75th percentiles of the risk-standardized mortality rate were
      8.5% and 9.7%, with 5th and 95th percentiles of 7.6% and 11.0%. In the derivation
      cohort of the no ST-segment elevation myocardial infarction and no shock model
      (n=110 529), the unadjusted 30-day mortality rate was 1.4%. The final model
      included 16 variables with the observed predicted mortality rates ranging from
      0.1% to 7.0% across deciles of the predicted patient mortality rates. The 25th
      and 75th percentiles of the risk-standardized mortality rate across 612 hospitals
      were 1.3% and 1.6%, with 5th and 95th percentiles of 1.0% and 2.0%. CONCLUSIONS:
      These National Quality Forum endorsed registry-based models produce estimates of
      hospital risk-standardized mortality rates for patients undergoing PCI.

PMID- 22949492
TI  - Five-year clinical and economic outcomes among patients with medically managed
      severe aortic stenosis: results from a Medicare claims analysis.
AB  - BACKGROUND: Patients with severe, symptomatic aortic stenosis, who do not undergo
      valve replacement surgery have a poor long-term prognosis. Limited data exist on
      the medical resource utilization and costs during the final stages of the
      disease. METHODS AND RESULTS: We used data from the 2003 Medicare 5% standard
      analytic files to identify patients with aortic stenosis and a recent
      hospitalization for heart failure, who did not undergo valve replacement surgery
      within the ensuing 2 calendar quarters. These patients (n=2150) were considered
      to have medically managed severe aortic stenosis and were tracked over 5 years to
      measure clinical outcomes, medical resource use, and costs (from the perspective
      of the Medicare Program). The mean age of the cohort was 82 years, 64% were
      female, and the estimated logistic European System for Cardiac Operative Risk
      Evaluation (EuroSCORE) (a measure of predicted mortality with cardiac surgery)
      was 17%. During 5 years of follow-up, overall mortality was 88.4% with a mean
      survival duration of 1.8 years. During this time period, patients experienced an
      average of 4.4 hospital admissions, 52% were admitted to skilled nursing care,
      and 28% were admitted to hospice care. The total 5-year costs were $63 844 per
      patient, whereas mean annual follow-up costs (excluding the index quarter) per
      year alive were $29 278. CONCLUSIONS: Elderly patients with severe aortic
      stenosis undergoing medical management have limited long-term survival and incur
      substantial costs to the Medicare Program. These results have important
      implications for policy makers interested in better understanding the cost
      effectiveness of emerging treatment options such as transcatheter aortic valve
      replacement.

PMID- 22949493
TI  - Guideline adherence after ST-segment elevation versus non-ST segment elevation
      myocardial infarction.
AB  - BACKGROUND: Clinical guidelines recommend similar medical therapy for patients
      with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment
      elevation MI (NSTEMI). METHODS AND RESULTS: Using the Get with the Guidelines
      Coronary Artery Disease registry (GWTG-CAD), we analyzed data including 72 352
      patients (48 966, NSTEMI; 23 386, STEMI) from 237 US sites between May 1, 2006
      and March 21, 2010. Performance and quality measures were compared between NSTEMI
      and STEMI patients. NSTEMI patients were older and had a higher rate of medical
      comorbidities compared with STEMI patients, including prior coronary artery
      disease (38.5% versus 24.7%; P<0.0001), heart failure (17.5% versus 6.2%;
      P<0.0001), hypertension (70.8% versus 59.1%; P<0.0001) and diabetes mellitus
      (34.9 versus 23.3%; P<0.0001). Adjusting for confounding variables, STEMI
      patients were more likely to receive aspirin within 24 hours 98.5% versus 97.1%
      (adjusted odds ratio [AOR], 1.63; 95% confidence interval [CI], 1.32-2.02), be
      discharged on aspirin 98.5% versus 97.3% (AOR, 1.33; 95% CI, 1.19-1.49), beta
      blockers 98.2% versus 96.9% (AOR, 1.48; 95% CI, 1.35-1.63), or lipid-lowering
      medication for low-density lipoprotein level >100 mg/dL 96.8% versus 91.0% (AOR,
      1.85; 95% CI, 1.61-2.13). STEMI patients were also more likely to receive beta
      blockers within 24 hours of hospital arrival 93.9% versus 90.8% (AOR, 1.57; 95%
      CI, 1.37-1.79) and the following discharge medications: angiotensin-converting
      enzyme inhibitors or angiotensin receptor blocking agents 85.3% versus 77.4%
      (AOR, 1.62; 95% CI, 1.51-1.75), clopidogrel 85.6% versus 67.0% (AOR, 2.42; 95%
      CI, 2.23-2.61) or lipid-lowering medications 94.8% versus 88.0% (AOR, 1.71; 95%
      CI, 1.56-1.86). CONCLUSIONS: Among hospitals participating in GWTG-CAD, adherence
      with guideline-based medical therapy was high for patients with both STEMI and
      NSTEMI. Yet, there is still room for further improvement, particularly in the
      care of NSTEMI patients.

PMID- 22949494
TI  - Impact of door-to-activation time on door-to-balloon time in primary percutaneous
      coronary intervention for ST-segment elevation myocardial infarctions: a report
      from the Activate-SF registry.
AB  - BACKGROUND: Little is known about the components of door-to-balloon time among
      patients with ST-segment elevation myocardial infarction undergoing primary
      percutaneous coronary intervention. We assessed the role of time from hospital
      arrival to ST-segment elevation myocardial infarction diagnosis (door-to
      activation time) on door-to-balloon time in contemporary practice and evaluated
      factors that influence door-to-activation times. METHODS AND RESULTS: Registry
      data on 347 consecutive patients diagnosed with a ST-segment elevation myocardial
      infarction in the emergency department over 30 months at 2 urban primary
      percutaneous coronary intervention centers were analyzed. The primary study end
      point was the time from hospital arrival to catheterization laboratory activation
      by the emergency department physician, and we assessed factors associated with
      this period. Door-to-balloon time and its other components were secondary study
      end points. The median door-to-activation time was 19 minutes (interquartile
      range, 9-54). Variation in door-to-activation times explained 93% of the
      variation in door-to-balloon times and demonstrated the strongest correlation
      with door-to-balloon times (r=0.97). Achieving a door-to-activation time of <=20
      minutes resulted in an 89% chance of achieving a door-to-balloon time of <=90
      minutes compared with only 28% for patients with a door-to-activation time >20
      minutes. Factors significantly associated with door-to-activation time include
      the following: prehospital ECG use (61% shorter, 95% confidence interval, -50 to 
      72%; P<0.001) and computed tomography scan use in the emergency department (245%
      longer, 95% confidence interval, +50 to +399%; P=0.001). CONCLUSIONS: The
      interval from hospital arrival to ST-segment elevation myocardial infarction
      diagnosis and catheterization laboratory activation (door-to-activation time) is
      a strong driver of overall door-to-balloon times. Achieving a door-to-activation
      time <=20 minutes was key to achieving a door-to-balloon time <=90 minutes.
      Delays in door-to-activation time are not associated with delays in other aspects
      of the primary percutaneous coronary intervention process.

PMID- 22949495
TI  - Left ventricular ejection fraction assessment among patients with acute
      myocardial infarction and its association with hospital quality of care and
      evidence-based therapy use.
AB  - BACKGROUND: The left ventricular ejection fraction (LVEF) has prognostic and
      therapeutic utility after acute myocardial infarction (AMI). Although LVEF
      assessment is a key performance measure among AMI patients, contemporary rates of
      in-hospital assessment and its association with therapy use have not been well
      characterized. METHODS AND RESULTS: We examined rates of in-hospital LVEF
      assessment among 77 982 non-ST-elevation myocardial infarction patients and 50
      863 ST-elevation myocardial infarction patients in Acute Coronary Treatment and
      Intervention Outcomes Network Registry-Get With The Guidelines between January
      2007 and September 2009, after excluding patients who died in-hospital or who
      were transferred to another acute care facility, discharged to end-of-life care,
      or had missing LVEF assessment status. LVEF assessment increased significantly
      over time, with higher rates among ST-elevation myocardial infarction than non-ST
      elevation myocardial infarction patients (95.1% versus 91.6%; P<0.001). Excluding
      patients with prior heart failure did not alter these observations. Significant
      interhospital variability in LVEF assessment rates was observed. Compared with
      patients with in-hospital LVEF assessment, patients who did not have LVEF
      assessed were older and more likely to have clinical comorbidities. In
      multivariable modeling, lower overall hospital quality of AMI care was also
      associated with lower likelihood of LVEF assessment (odds ratio for failure to
      assess LVEF, 1.09; 95% confidence interval, 1.05-1.13 per 10% decrease in defect
      free care). Patients with in-hospital LVEF assessment were more likely to be
      discharged on evidence-based secondary prevention medication therapies compared
      with patients without LVEF assessment. CONCLUSIONS: The assessment of LVEF among
      patients with AMI has improved significantly over time, yet significant
      interhospital variability exists. Patients who did not have in-hospital LVEF
      assessment were less likely to receive evidence-based medications at discharge.
      These patients represent targets for future quality improvement efforts.

PMID- 22949496
TI  - Assessing secondhand smoke exposure with reported measures.
AB  - Non-smokers are exposed to tobacco smoke from the burning cigarette and the
      exhaled smoke from smokers. In spite of decades of development of approaches to
      assess secondhand smoke exposure (SHSe), there are still unresolved
      methodological issues. This manuscript summarises the scientific evidence on the
      use of SHSe reported measures and their methods, objectives, strengths and
      limitations; and discusses best practices for assessing behaviour leading to SHSe
      for lifetime and immediate or current SHSe. Recommendations for advancing
      measurement science of SHSe are provided. Behavioural measures of SHSe commonly
      rely on self-reports from children and adults. Most commonly, the methodology
      includes self, proxy and interview-based reporting styles using retrospective
      recall or diary-style reporting formats. The reporting method used will vary
      based upon the subject of interest, assessment objectives and cultural context.
      Appropriately implemented, reported measures of SHSe provide an accurate, timely
      and cost-effective method for assessing exposure time, location and quantity in a
      wide variety of populations.

PMID- 22949497
TI  - Environmental monitoring of secondhand smoke exposure.
AB  - The complex composition of secondhand smoke (SHS) provides a range of
      constituents that can be measured in environmental samples (air, dust and on
      surfaces) and therefore used to assess non-smokers' exposure to tobacco smoke.
      Monitoring SHS exposure (SHSe) in indoor environments provides useful information
      on the extent and consequences of SHSe, implementing and evaluating tobacco
      control programmes and behavioural interventions, and estimating overall burden
      of disease caused by SHSe. The most widely used markers have been vapour-phase
      nicotine and respirable particulate matter (PM). Numerous other environmental
      analytes of SHS have been measured in the air including carbon monoxide, 3
      ethenylpyridine, polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines,
      nitrogen oxides, aldehydes and volatile organic compounds, as well as nicotine in
      dust and on surfaces. The measurement of nicotine in the air has the advantage of
      reflecting the presence of tobacco smoke. While PM measurements are not as
      specific, they can be taken continuously, allowing for assessment of exposure and
      its variation over time. In general, when nicotine and PM are measured in the
      same setting using a common sampling period, an increase in nicotine
      concentration of 1 MUg/m(3) corresponds to an average increase of 10 MUg/m3 of
      PM. This topic assessment presents a comprehensive summary of SHSe monitoring
      approaches using environmental markers and discusses the strengths and weaknesses
      of these methods and approaches.

PMID- 22949498
TI  - Television watching, leisure time physical activity, and the genetic
      predisposition in relation to body mass index in women and men.
AB  - BACKGROUND: Previous studies on gene-lifestyle interaction and obesity have
      focused mostly on the FTO gene and physical activity, whereas little attention
      has been paid to sedentary behavior as indicated by television (TV) watching.
      METHODS AND RESULTS: We analyzed interactions between TV watching, leisure time
      physical activity, and genetic predisposition in relation to body mass index
      (BMI) in 7740 women and 4564 men from 2 prospective cohorts: The Nurses' Health
      Study and the Health Professionals Follow-up Study. Data on physical activity and
      TV watching were collected 2 years before assessment of BMI. A weighted genetic
      risk score was calculated on the basis of 32 established BMI-associated variants.
      In both women and men, the genetic associations with BMI strengthened with
      increased hours of TV watching. An increment of 10 points in the weighted genetic
      risk score was associated with 0.8 (SE, 0.4), 0.8 (SE, 0.2), 1.4 (SE, 0.2), 1.5
      (SE, 0.2), and 3.4 (SE, 1.0) kg/m(2) higher BMI across the 5 categories of TV
      watching (0-1, 2-5, 6-20, 21-40, and >40 h/wk; P for interaction=0.001). In
      contrast, the genetic association with BMI weakened with increased levels of
      physical activity. An increment of 10 points in the weighted genetic risk score
      was associated with 1.5 (SE, 0.2), 1.3 (SE, 0.2), 1.2 (SE, 0.2), 1.2 (SE, 0.2),
      and 0.8 (SE, 0.2) kg/m(2) higher BMI across the quintiles of physical activity.
      The interactions of TV watching and physical activity with genetic predisposition
      in relation to BMI were independent of each other. CONCLUSIONS: A sedentary
      lifestyle, indicated by prolonged TV watching, may accentuate the predisposition
      to elevated adiposity, whereas greater leisure time physical activity may
      attenuate the genetic association.

PMID- 22949499
TI  - Development and functionality of a handheld computer program to improve fruit and
      vegetable intake among low-income youth.
AB  - Mobile technologies hold promise for improving diet and physical activity, but
      little attention is given to creating programs that adolescents like and will
      use. This study developed a personal digital assistant (PDA) program to promote
      increased intake of fruits and vegetables (FV) in predominately low-income,
      ethnic minority girls. This study used a three-phase community-engaged process,
      including (i) engagement of a Student Advisory Board (SAB) to determine comfort
      with PDAs; (ii) early testing of Prototype I and rapid re-design by the SAB and
      (iii) feasibility testing of Prototype II in a new sample of girls. Phase 1
      results showed that girls were comfortable with the PDA. Testing of Prototype I
      in Phase 2 showed that acceptability was mixed, with girls responding to 47.3% of
      the prompts. Girls wanted more reminders, accountability in monitoring FV, help
      in meeting daily goals and free music downloads based on program use. The PDA was
      reprogrammed and testing of Prototype II in Phase 3 demonstrated marked
      improvement in use (78.3%), increases in FV intake (1.8 +/- 2.6 daily servings)
      and good overall satisfaction. Findings suggest that mobile technology designed
      with the early input of youth is a promising way to improve adolescent health
      behaviors.

PMID- 22949500
TI  - Identifying critical sun-protective beliefs among Australian adults.
AB  - We investigated critical beliefs to target in interventions aimed at improving
      sun-protective behaviours of Australian adults, a population at risk for skin
      cancer. Participants (N = 816) completed a Theory of Planned Behaviour belief
      based questionnaire and a 1-week follow-up of sun-protective behaviour. A range
      of behavioural, normative and control beliefs correlated with sun-protective
      behaviour, with no and only minimal differences observed in correlations between
      beliefs and behaviour by gender and age, respectively. A range of key beliefs
      made independent contributions to behaviour; however, the behavioural belief
      about being less likely to tan (beta = 0.09); normative belief about friends
      (beta = 0.20); and control beliefs about forgetfulness (beta = -0.14),
      inconvenience (beta = -0.17), knowing I will be in the sun for a long time (beta
      = 0.16) and more fashionable sun-protective clothing (beta = 0.13) were
      significant critical beliefs guiding people's sun-protective behaviour. Our study
      fills a gap in the literature by investigating an at-risk population for skin
      cancer and using an established theoretical framework to identify critical
      beliefs that guide Australian adults' decisions to sun protect. Attention to
      these critical beliefs will assist health campaigns and interventions aimed at
      combating the increasing rates of skin cancer for adults.

PMID- 22949501
TI  - Genetic evidence of an evolutionarily conserved role for Nrf2 in the protection
      against oxidative stress.
AB  - Transcription factor Nrf2 is considered a master regulator of antioxidant defense
      in mammals. However, it is unclear whether this concept is applicable to
      nonmammalian vertebrates, because no animal model other than Nrf2 knockout mice
      has been generated to examine the effects of Nrf2 deficiency. Here, we
      characterized a recessive loss-of-function mutant of Nrf2 (nrf2(fh318)) in a
      lower vertebrate, the zebrafish (Danio rerio). In keeping with the findings in
      the mouse model, nrf2(fh318) mutants exhibited reduced induction of the Nrf2
      target genes in response to oxidative stress and electrophiles but were viable
      and fertile, and their embryos developed normally. The nrf2(fh318) larvae
      displayed enhanced sensitivity to oxidative stress and electrophiles, especially
      peroxides, and pretreatment with an Nrf2-activating compound, sulforaphane,
      decreased peroxide-induced lethality in the wild type but not nrf2(fh318)
      mutants, indicating that resistance to oxidative stress is highly dependent on
      Nrf2 functions. These results reveal an evolutionarily conserved role of
      vertebrate Nrf2 in protection against oxidative stress. Interestingly, there were
      no significant differences between wild-type and nrf2(fh318) larvae with regard
      to their sensitivity to superoxide and singlet oxygen generators, suggesting that
      the importance of Nrf2 in oxidative stress protection varies based on the type of
      reactive oxygen species (ROS).

PMID- 22949502
TI  - A novel mechanism for the autonomous termination of pre-B cell receptor
      expression via induction of lysosome-associated protein transmembrane 5.
AB  - The expression of the pre-B cell receptor (BCR) is confined to the early stage of
      B cell development, and its dysregulation is associated with anomalies of B
      lineage cells, including leukemogenesis. Previous studies suggested that the pre
      BCR signal might trigger the autonomous termination of pre-BCR expression even
      before the silencing of pre-BCR gene expression to prevent sustained pre-BCR
      expression. However, the underlying mechanism remains ill defined. Here we
      demonstrate that the pre-BCR signal induces the expression of lysosome-associated
      protein transmembrane 5 (LAPTM5), which leads to the prompt downmodulation of the
      pre-BCR. While LAPTM5 induction had no significant impact on the internalization
      of cell surface pre-BCR, it elicited the translocation of a large pool of
      intracellular pre-BCR from the endoplasmic reticulum to the lysosomal compartment
      concomitantly with a drastic reduction of the level of intracellular pre-BCR
      proteins. This reduction was inhibited by lysosomal inhibitors, indicating the
      lysosomal degradation of the pre-BCR. Notably, the LAPTM5 deficiency in pre-B
      cells led to the augmented expression level of surface pre-BCR. Collectively, the
      pre-BCR induces the prompt downmodulation of its own expression through the
      induction of LAPTM5, which promotes the lysosomal transport and degradation of
      the intracellular pre-BCR pool and, hence, limits the supply of pre-BCR to the
      cell surface.

PMID- 22949503
TI  - Ablation of ALCAT1 mitigates hypertrophic cardiomyopathy through effects on
      oxidative stress and mitophagy.
AB  - Oxidative stress causes mitochondrial dysfunction and  heart failure through
      unknown mechanisms. Cardiolipin (CL), a mitochondrial membrane phospholipid
      required for oxidative phosphorylation, plays a pivotal role in cardiac function.
      The onset of age-related heart diseases is characterized by aberrant CL acyl
      composition that is highly sensitive to oxidative damage, leading to CL
      peroxidation and mitochondrial dysfunction. Here we report a key role of ALCAT1,
      a lysocardiolipin acyltransferase that catalyzes the synthesis of CL with a high
      peroxidation index, in mitochondrial dysfunction associated with hypertrophic
      cardiomyopathy. We show that ALCAT1 expression was potently upregulated by the
      onset of hyperthyroid cardiomyopathy, leading to oxidative stress and
      mitochondrial dysfunction. Accordingly, overexpression of ALCAT1 in H9c2 cardiac
      cells caused severe oxidative stress, lipid peroxidation, and mitochondrial DNA
      (mtDNA) depletion. Conversely, ablation of ALCAT1 prevented the onset of T4
      induced cardiomyopathy and cardiac dysfunction. ALCAT1 deficiency also mitigated
      oxidative stress, insulin resistance, and mitochondrial dysfunction by improving
      mitochondrial quality control through upregulation of PINK1, a mitochondrial
      GTPase required for mitochondrial autophagy. Together, these findings implicate a
      key role of ALCAT1 as the missing link between oxidative stress and mitochondrial
      dysfunction in the etiology of age-related heart diseases.

PMID- 22949504
TI  - HtrA1 is a novel antagonist controlling fibroblast growth factor (FGF) signaling
      via cleavage of FGF8.
AB  - Accumulating evidence suggests that HtrA1 (high-temperature requirement A1) is
      involved in modulating crucial cellular processes and implicated in life
      threatening diseases, such as cancer and neuropathological disorders; however,
      the exact functions of this protease in vivo remain unknown. Here, we show that
      loss of HtrA1 function increases fibroblast growth factor 8 (FGF8) mRNA levels
      and triggers activation of FGF signaling, resulting in dorsalization in zebrafish
      embryos. Notably, HtrA1 directly cleaves FGF8 in the extracellular region, and
      this cleavage results in decreased activation of FGF signaling, which is
      essential for many physiological processes. Therefore, HtrA1 is indispensable for
      dorsoventral patterning in early zebrafish embryogenesis and serves as a key
      upstream regulator of FGF signaling through the control of FGF levels.
      Furthermore, this study offers insight into new strategies to control human
      diseases associated with HtrA1 and FGF signaling.

PMID- 22949505
TI  - Oxidative stress responses involve oxidation of a conserved ubiquitin pathway
      enzyme.
AB  - Although it is vital that cells detect and respond to oxidative stress to allow
      adaptation and repair damage, the underlying sensing and signaling mechanisms
      that control these responses are unclear. Protein ubiquitinylation plays an
      important role in controlling many biological processes, including cell division.
      In Saccharomyces cerevisiae, ubiquitinylation involves a single E1 enzyme, Uba1,
      with multiple E2s and E3s providing substrate specificity. For instance, the
      conserved E2 Cdc34 ubiquitinylates many substrates, including the cyclin
      dependent kinase inhibitor Sic1, targeting it for degradation to allow cell cycle
      progression. Here we reveal that, in contrast to other ubiquitin pathway E2
      enzymes, Cdc34 is particularly sensitive to oxidative inactivation, through
      sequestration of the catalytic cysteine in a disulfide complex with Uba1, by
      levels of oxidant that do not reduce global ubiquitinylation of proteins. This
      Cdc34 oxidation is associated with (i) reduced levels of Cdc34-ubiquitin
      thioester forms, (ii) increased stability of at least one Cdc34 substrate, Sic1,
      and (iii) Sic1-dependent delay in cell cycle progression. Together, these data
      reveal that the differential sensitivity of a ubiquitin pathway E2 enzyme to
      oxidation is utilized as a stress-sensing mechanism to respond to oxidative
      stress.

PMID- 22949506
TI  - Geminin regulates the transcriptional and epigenetic status of neuronal fate
      promoting genes during mammalian neurogenesis.
AB  - Regulating the transition from lineage-restricted progenitors to terminally
      differentiated cells is a central aspect of nervous system development. Here, we
      investigated the role of the nucleoprotein geminin in regulating neurogenesis at
      a mechanistic level during both Xenopus primary neurogenesis and mammalian
      neuronal differentiation in vitro. The latter work utilized neural cells derived
      from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells
      from mouse forebrain. In all of these contexts, geminin antagonized the ability
      of neural basic helix-loop-helix (bHLH) transcription factors to activate
      transcriptional programs promoting neurogenesis. Furthermore, geminin promoted a
      bivalent chromatin state, characterized by the presence of both activating and
      repressive histone modifications, at genes encoding transcription factors that
      promote neurogenesis. This epigenetic state restrains the expression of genes
      that regulate commitment of undifferentiated stem and neuronal precursor cells to
      neuronal lineages. However, maintaining geminin at high levels was not sufficient
      to prevent terminal neuronal differentiation. Therefore, these data support a
      model whereby geminin promotes the neuronal precursor cell state by modulating
      both the epigenetic status and expression of genes encoding neurogenesis
      promoting factors. Additional developmental signals acting in these cells can
      then control their transition toward terminal neuronal or glial differentiation
      during mammalian neurogenesis.

PMID- 22949507
TI  - Essential roles of Da transactivation domains in neurogenesis and in E(spl)
      mediated repression.
AB  - E proteins are a special class of basic helix-loop-helix (bHLH) proteins that
      heterodimerize with many bHLH activators to regulate developmental decisions,
      such as myogenesis and neurogenesis. Daughterless (Da) is the sole E protein in
      Drosophila and is ubiquitously expressed. We have characterized two transcription
      activation domains (TADs) in Da, called activation domain 1 (AD1) and loop-helix
      (LH), and have evaluated their roles in promoting peripheral neurogenesis. In
      this context, Da heterodimerizes with proneural proteins, such as Scute (Sc),
      which is dynamically expressed and also contributes a TAD. We found that either
      one of the Da TADs in the Da/Sc complex is sufficient to promote neurogenesis,
      whereas the Sc TAD is incapable of doing so. Besides its transcriptional
      activation role, the Da AD1 domain serves as an interaction platform for E(spl)
      proteins, bHLH-Orange family repressors which antagonize Da/Sc function. We show
      that the E(spl) Orange domain is needed for this interaction and strongly
      contributes to the antiproneural activity of E(spl) proteins. We present a
      mechanistic model on the interplay of these bHLH factors in the context of neural
      fate assignment.

PMID- 22949508
TI  - Caspase-3 protects stressed organs against cell death.
AB  - The ability to generate appropriate defense responses is crucial for the survival
      of an organism exposed to pathogenesis-inducing insults. However, the mechanisms
      that allow tissues and organs to cope with such stresses are poorly understood.
      Here we show that caspase-3-knockout mice or caspase inhibitor-treated mice were
      defective in activating the antiapoptotic Akt kinase in response to various
      chemical and environmental stresses causing sunburns, cardiomyopathy, or colitis.
      Defective Akt activation in caspase-3-knockout mice was accompanied by increased
      cell death and impaired survival in some cases. Mice homozygous for a mutation in
      RasGAP that prevents its cleavage by caspase-3 exhibited a similar defect in Akt
      activation, leading to increased apoptosis in stressed organs, marked
      deterioration of their physiological functions, and stronger disease development.
      Our results provide evidence for the relevance of caspase-3 as a stress intensity
      sensor that controls cell fate by either initiating a RasGAP cleavage-dependent
      cell resistance program or a cell suicide response.

PMID- 22949509
TI  - The PRoteomics IDEntification (PRIDE) Converter 2 framework: an improved suite of
      tools to facilitate data submission to the PRIDE database and the ProteomeXchange
      consortium.
AB  - The original PRIDE Converter tool greatly simplified the process of submitting
      mass spectrometry (MS)-based proteomics data to the PRIDE database. However,
      after much user feedback, it was noted that the tool had some limitations and
      could not handle several user requirements that were now becoming commonplace.
      This prompted us to design and implement a whole new suite of tools that would
      build on the successes of the original PRIDE Converter and allow users to
      generate submission-ready, well-annotated PRIDE XML files. The PRIDE Converter 2
      tool suite allows users to convert search result files into PRIDE XML (the format
      needed for performing submissions to the PRIDE database), generate mzTab skeleton
      files that can be used as a basis to submit quantitative and gel-based MS data,
      and post-process PRIDE XML files by filtering out contaminants and empty spectra,
      or by merging several PRIDE XML files together. All the tools have both a
      graphical user interface that provides a dialog-based, user-friendly way to
      convert and prepare files for submission, as well as a command-line interface
      that can be used to integrate the tools into existing or novel pipelines, for
      batch processing and power users. The PRIDE Converter 2 tool suite will thus
      become a cornerstone in the submission process to PRIDE and, by extension, to the
      ProteomeXchange consortium of MS-proteomics data repositories.

PMID- 22949510
TI  - Mutant Twinkle increases dopaminergic neurodegeneration, mtDNA deletions and
      modulates Parkin expression.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder in
      the developed world, and is characterized by the loss of dopaminergic (DA)
      neurons in the substantia nigra (SN). Somatic mitochondrial DNA (mtDNA) deletions
      reach their highest concentration with age in the SN in humans, and may
      contribute to PD; yet whether mtDNA deletions cause DA neuron degeneration
      remains unclear. Inherited mutations of Twinkle helicase involved in mtDNA
      replication causes a dominant increase in mtDNA deletions in humans. We
      constructed a mouse model expressing mutant Twinkle in DA neurons. Mutant mice
      had an increase in age-related mtDNA deletions, reduction of DA neuron number in
      SN at 17-22 months and displayed abnormalities in rota-rod behavior. Functional
      analysis of midbrain indicated a slight reduction in mitochondrial state II
      respiration in mutants, but no decrease in maximal respiration. Also, Parkin
      expression was significantly decreased in DA neurons in the SN of 22-month-old
      mutant mice, and in PC12 cells after 48 h transfection of mutant Twinkle. Both
      confocal imaging and coimmunoprecipitation indicated interaction of Twinkle with
      Parkin in the mitochondria. Parkin overexpression rescued the reduction of
      proteasome activity caused by mutant Twinkle in PC12 cells. In addition, the
      autophagy marker LC3 was increased in the SN of 22-month transgenics, and this
      increase was similarly mutant Twinkle-dependent in PC12 cells. Collectively, our
      data demonstrate that mammalian Twinkle is important for mitochondrial integrity
      in DA neurons and provide a novel mouse model in which increased mtDNA deletions
      may lead to DA neuron degeneration and parkinsonism.

PMID- 22949512
TI  - Reduced cathepsins B and D cause impaired autophagic degradation that can be
      almost completely restored by overexpression of these two proteases in Sap C
      deficient fibroblasts.
AB  - Saposin (Sap) C deficiency, a rare variant form of Gaucher disease, is due to
      mutations in the Sap C coding region of the prosaposin (PSAP) gene. Sap C is
      required as an activator of the lysosomal enzyme glucosylceramidase (GCase),
      which catalyzes glucosylceramide (GC) degradation. Deficit of either GCase or Sap
      C leads to the accumulation of undegraded GC and other lipids in lysosomes of
      monocyte/macrophage lineage. Recently, we reported that Sap C mutations affecting
      a cysteine residue result in increased autophagy. Here, we characterized the
      basis for the autophagic dysfunction. We analyzed Sap C-deficient and GCase
      deficient fibroblasts and observed that autophagic disturbance was only
      associated with lack of Sap C. By a combined fluorescence microscopy and
      biochemical studies, we demonstrated that the accumulation of autophagosomes in
      Sap C-deficient fibroblasts is not due to enhanced autophagosome formation but to
      delayed degradation of autolysosomes caused, in part, to decreased amount and
      reduced enzymatic activity of cathepsins B and D. On the contrary, in GCase
      deficient fibroblasts, the protein level and enzymatic activity of cathepsin D
      were comparable with control fibroblasts, whereas those of cathepsin B were
      almost doubled. Moreover, the enhanced expression of both these lysosomal
      proteases in Sap C-deficient fibroblasts resulted in close to functional
      autophagic degradation. Our data provide a novel example of altered autophagy as
      secondary event resulting from insufficient lysosomal function.

PMID- 22949511
TI  - Mutations in FKBP10, which result in Bruck syndrome and recessive forms of
      osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone
      collagen.
AB  - Although biallelic mutations in non-collagen genes account for <10% of
      individuals with osteogenesis imperfecta, the characterization of these genes has
      identified new pathways and potential interventions that could benefit even those
      with mutations in type I collagen genes. We identified mutations in FKBP10, which
      encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21
      families with OI. These include 10 families from the Samoan Islands who share a
      founder mutation. Of the mutations, three are missense; the remainder either
      introduce premature termination codons or create frameshifts both of which result
      in mRNA instability. In four families missense mutations result in loss of most
      of the protein. The clinical effects of these mutations are short stature, a high
      incidence of joint contractures at birth and progressive scoliosis and fractures,
      but there is remarkable variability in phenotype even within families. The loss
      of the activity of FKBP65 has several effects: type I procollagen secretion is
      slightly delayed, the stabilization of the intact trimer is incomplete and there
      is diminished hydroxylation of the telopeptide lysyl residues involved in
      intermolecular cross-link formation in bone. The phenotype overlaps with that
      seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme
      that hydroxylates the telopeptide lysyl residues. These findings define a set of
      genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to
      contribute to molecular stability and post-translational modification of type I
      procollagen, without which bone mass and quality are abnormal and fractures and
      contractures result.

PMID- 22949513
TI  - Genome-wide association analysis of genetic generalized epilepsies implicates
      susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.
AB  - Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and
      account for 20-30% of all epilepsies. Despite their high heritability of 80%, the
      genetic factors predisposing to GGEs remain elusive. To identify susceptibility
      variants shared across common GGE syndromes, we carried out a two-stage genome
      wide association study (GWAS) including 3020 patients with GGEs and 3954 controls
      of European ancestry. To dissect out syndrome-related variants, we also explored
      two distinct GGE subgroups comprising 1434 patients with genetic absence
      epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint
      Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at
      2p16.1 (rs13026414, P(meta) = 2.5 * 10(-9), OR[T] = 0.81) and 17q21.32
      (rs72823592, P(meta) = 9.3 * 10(-9), OR[A] = 0.77). The search for syndrome
      related susceptibility alleles identified significant associations for GAEs at
      2q22.3 (rs10496964, P(meta) = 9.1 * 10(-9), OR[T] = 0.68) and at 1q43 for JME
      (rs12059546, P(meta) = 4.1 * 10(-8), OR[G] = 1.42). Suggestive evidence for an
      association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 *
      10(-6)) nearby the SCN1A gene, which is currently the gene with the largest
      number of known epilepsy-related mutations. The associated regions harbor high
      ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at
      2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to
      elucidate whether these positional candidate genes contribute to the heritability
      of the common GGE syndromes.

PMID- 22949514
TI  - Expression of SMARCB1 (INI1) mutations in familial schwannomatosis.
AB  - Genetic changes in the SMARCB1 tumor suppressor gene have recently been reported
      in tumors and blood from families with schwannomatosis. Exon scanning of all nine
      SMARCB1 exons in genomic DNA from our cohort of families meeting the criteria for
      'definite' or 'presumptive' schwannomatosis previously revealed constitutional
      alterations in 13 of 19 families (68%). Screening of four new familial
      schwannomatosis probands identified one additional constitutional alteration. We
      confirmed the presence of mRNA transcripts for two missense alterations, four
      mutations of conserved splice motifs and two additional mutations, in less
      conserved sequences, which also affect splicing. Furthermore, we found that
      transcripts for a rare 3'-untranslated region (c.*82C > T) alteration shared by
      four unrelated families did not produce splice variants but did show unequal
      allelic expression, suggesting that the alteration is either causative itself or
      linked to an unidentified causative mutation. Overexpression studies in cells
      lacking SMARCB1 suggest that mutant SMARCB1 proteins, like wild-type SMARCB1
      protein, retain the ability to suppress cyclin D1 activity. These data, together
      with the expression of SMARCB1 protein in a proportion of cells from
      schwannomatosis-related schwannomas, suggest that these tumors develop through a
      mechanism that is distinct from that of rhabdoid tumors in which SMARCB1 protein
      is completely absent in tumor cells.

PMID- 22949515
TI  - Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship
      with thrombocytopenia, endothelial activation, and vascular stability.
AB  - The pathogenesis of plasma leakage during dengue hemorrhagic fever/dengue shock
      syndrome (DHF/DSS) is largely unknown. Angiopoietins are key regulators of
      vascular integrity: Angiopoietin-1 is stored in platelets and maintains vascular
      integrity, and endothelium-derived angiopoietin-2 promotes vascular leakage. We
      determined angiopoietin-1 and angiopoietin-2 levels in a cohort of children in
      Indonesia with DHF/DSS and related them to plasma leakage markers. Patients with
      DHF/DSS had reduced angiopoietin-1 and increased angiopoietin-2 plasma levels on
      the day of admission when compared with levels at discharge and in healthy
      controls. There was an inverse correlation between angiopoietin-1 and markers of
      plasma leakage and a positive correlation between angiopoietin-2 and markers of
      plasma leakage. Angiopoietin-1 levels followed the same trend as the soluble
      platelet activation marker P-selectin and correlated with platelet counts. Dengue
      associated thrombocytopenia and endothelial activation are associated with an
      imbalance in angiopoietin-2: angiopoietin-1 plasma levels. This imbalance may
      contribute to the transient plasma leakage in DHF/DSS.

PMID- 22949516
TI  - Single-nucleotide polymorphism and copy number variation of the multidrug
      resistance-1 locus of Plasmodium vivax: local and global patterns.
AB  - Emerging resistance to chloroquine (CQ) poses a major challenge for Plasmodium
      vivax malaria control, and nucleotide substitutions and copy number variation in
      the P. vivax multidrug resistance 1 (pvmdr-1) locus, which encodes a digestive
      vacuole membrane transporter, may modulate this phenotype. We describe patterns
      of genetic variation in pvmdr-1 alleles from Acre and Amazonas in northwestern
      Brazil, and compare then with those reported in other malaria-endemic regions.
      The pvmdr-1 mutation Y976F, which is associated with CQ resistance in Southeast
      Asia and Oceania, remains rare in northwestern Brazil (1.8%) and its prevalence
      mirrors that of CQ resistance worldwide. Gene amplification of pvmdr-1, which is
      associated with mefloquine resistance but increased susceptibility to CQ, remains
      relatively rare in northwestern Brazil (0.9%) and globally (< 4%), but became
      common (> 10%) in Tak Province, Thailand, possibly because of drug-mediated
      selection. The global database we have assembled provides a baseline for further
      studies of genetic variation in pvmdr-1 and drug resistance in P. vivax malaria.

PMID- 22949517
TI  - Severe thrombotic events associated with dengue fever, Brazil.
AB  - Dengue fever has been a major problem in hospital settings in Brazil for the past
      15 years. The main concern has been the severe forms, i.e., dengue hemorrhagic
      fever and dengue shock syndrome. Hemorrhagic events of different degrees have
      also been a major concern. We report five cases of large vein thrombotic events
      associated with the acute phase of dengue fever, including a previously non
      reported case of mesenteric vein thrombosis. Complications such as these could
      have been overlooked in the diagnosis of dengue fever, given that the major
      concern is the hemorrhagic event.

PMID- 22949518
TI  - Genetic population structure of cercariae from an urban foci of Schistosoma
      mansoni, Brazil.
AB  - Rapid urbanization in Brazil has meant that many persons from rural areas where
      Schistosoma mansoni is endemic have migrated to cities. Discovery of a focus of
      active transmission in the city of Salvador prompted a citywide survey for active
      and potential transmission sites. Cercariae shed from infected snails collected
      from four locations were used to determine how these samples were related and if
      they were representative of the parasite population infecting humans. Each
      cercarial collection was greatly differentiated from the others, and diversity
      was significantly lower when compared with eggs from natural human infections in
      one site. Egg samples collected 7 years apart in one neighborhood showed little
      differentiation (Jost's D = 0.01-0.03). Given the clonal nature of parasite
      reproduction in the snail host and the short-term acquisition of parasites,
      cercariae from collections at one time point are unlikely to be representative of
      the diversity in the human population.

PMID- 22949519
TI  - Genetic diversity of Anopheles triannulatus s.l. (Diptera: Culicidae) from
      northwestern and southeastern Colombia.
AB  - Anopheles triannulatus s.l. is a species complex, however in Colombia its
      taxonomic status is unclear. This study was conducted to understand the level of
      genetic differentiation or population structure of specimens of An. triannulatus
      s.l. from northwestern and southeastern Colombia. Cytochrome oxidase subunit I
      (COI) and internal transcribed spacer (ITS2) sequence analyses suggested high
      genetic differentiation between the NW and SE populations. A TCS network and
      Bayesian inference analysis based on 814 bp of COI showed two main groups: group
      I included samples from the NW and group II samples from the SE. Two main ITS2
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      patterns were found. Pattern I is present in both the NW and SE, and pattern II
      is found in the SE specimens. To further elucidate the taxonomic status of An.
      triannulatus s.l. in Colombia and how these COI lineages are related to the
      Triannulatus Complex species, the evaluation of immature stages, male genitalia,
      and additional mitochondrial and nuclear markers will be needed.

PMID- 22949520
TI  - Identification of immunodominant peptides from Gnathostoma binucleatum.
AB  - Gnathostomiasis is now recognized as a zoonosis with a worldwide distribution. In
      the Americas, it is caused by the third-stage larvae of Gnathostoma binucleatum
      and in Asia mainly by G. spinigerum. The availability and preparation of specific
      antigens are among the main obstacles for developing reliable immunodiagnostic
      tests. In this study, six immunodominant peptides were identified and
      characterized from G. binucleatum, somatic antigens (AgS: 24, 32, and 40 kDa) and
      excretory-secretory antigens (AgES: 42, 44, and 56 kDa) by two-dimensional
      immunoblot analysis. Among those immunodominant peptides, two AgS spots were
      characterized by mass spectrometric analysis (32 kDa; pI 6.3 and 6.5) and
      identified as type 1 galectins. In accordance with this finding, a fraction of
      AgS exhibited affinity to lactose and displayed a 100% specificity and
      sensitivity for the diagnosis of human gnathostomiasis.

PMID- 22949521
TI  - 9-Cis-retinoic acid induces growth inhibition in retinoid-sensitive breast cancer
      and sea urchin embryonic cells via retinoid X receptor alpha and replication
      factor C3.
AB  - There is widespread interest in defining factors and mechanisms that suppress the
      proliferation of cancer cells. Retinoic acid (RA) is a potent suppressor of
      mammary cancer and developmental embryonic cell proliferation. However, the
      molecular mechanisms by which 9-cis-RA signaling induces growth inhibition in RA
      sensitive breast cancer and embryonic cells are not apparent. Here, we provide
      evidence that the inhibitory effect of 9-cis-RA on cell proliferation depends on
      9-cis-RA-dependent interaction of retinoid X receptor alpha (RXRalpha) with
      replication factor C3 (RFC3), which is a subunit of the RFC heteropentamer that
      opens and closes the circular proliferating cell nuclear antigen (PCNA) clamp on
      DNA. An RFC3 ortholog in a sea urchin cDNA library was isolated by using the
      ligand-binding domain of RXRalpha as bait in a yeast two-hybrid screening. The
      interaction of RFC3 with RXRalpha depends on 9-cis-RA and bexarotene, but not on
      all-trans-RA or an RA receptor (RAR)-selective ligand. Truncation and mutagenesis
      experiments demonstrated that the C-terminal LXXLL motifs in both human and sea
      urchin RFC3 are critical for the interaction with RXRalpha. The transient
      interaction between 9-cis-RA-activated RXRalpha and RFC3 resulted in
      reconfiguration of the PCNA-RFC complex. Furthermore, we found that knockdown of
      RXRalpha or overexpression of RFC3 impairs the ability of 9-cis-RA to inhibit
      proliferation of MCF-7 breast cancer cells and sea urchin embryogenesis. Our
      results indicate that 9-cis-RA-activated RXRalpha suppresses the growth of RA
      sensitive breast cancer and embryonic cells through RFC3.

PMID- 22949523
TI  - Genomic evidence for large, long-lived ancestors to placental mammals.
AB  - It is widely assumed that our mammalian ancestors, which lived in the Cretaceous
      era, were tiny animals that survived massive asteroid impacts in shelters and
      evolved into modern forms after dinosaurs went extinct, 65 Ma. The small size of
      most Mesozoic mammalian fossils essentially supports this view. Paleontology,
      however, is not conclusive regarding the ancestry of extant mammals, because
      Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here,
      we use full-genome data to estimate the longevity and body mass of early
      placental mammals. Analyzing 36 fully sequenced mammalian genomes, we reconstruct
      two aspects of the ancestral genome dynamics, namely GC-content evolution and
      nonsynonymous over synonymous rate ratio. Linking these molecular evolutionary
      processes to life-history traits in modern species, we estimate that early
      placental mammals had a life span above 25 years and a body mass above 1 kg. This
      is similar to current primates, cetartiodactyls, or carnivores, but markedly
      different from mice or shrews, challenging the dominant view about mammalian
      origin and evolution. Our results imply that long-lived mammals existed in the
      Cretaceous era and were the most successful in evolution, opening new
      perspectives about the conditions for survival to the Cretaceous-Tertiary crisis.

PMID- 22949522
TI  - Whole-genome duplication and the functional diversification of teleost fish
      hemoglobins.
AB  - Subsequent to the two rounds of whole-genome duplication that occurred in the
      common ancestor of vertebrates, a third genome duplication occurred in the stem
      lineage of teleost fishes. This teleost-specific genome duplication (TGD) is
      thought to have provided genetic raw materials for the physiological,
      morphological, and behavioral diversification of this highly speciose group. The
      extreme physiological versatility of teleost fish is manifest in their diversity
      of blood-gas transport traits, which reflects the myriad solutions that have
      evolved to maintain tissue O(2) delivery in the face of changing metabolic
      demands and environmental O(2) availability during different ontogenetic stages.
      During the course of development, regulatory changes in blood-O(2) transport are
      mediated by the expression of multiple, functionally distinct hemoglobin (Hb)
      isoforms that meet the particular O(2)-transport challenges encountered by the
      developing embryo or fetus (in viviparous or oviparous species) and in free
      swimming larvae and adults. The main objective of the present study was to assess
      the relative contributions of whole-genome duplication, large-scale segmental
      duplication, and small-scale gene duplication in producing the extraordinary
      functional diversity of teleost Hbs. To accomplish this, we integrated
      phylogenetic reconstructions with analyses of conserved synteny to characterize
      the genomic organization and evolutionary history of the globin gene clusters of
      teleosts. These results were then integrated with available experimental data on
      functional properties and developmental patterns of stage-specific gene
      expression. Our results indicate that multiple alpha- and beta-globin genes were
      present in the common ancestor of gars (order Lepisoteiformes) and teleosts. The
      comparative genomic analysis revealed that teleosts possess a dual set of TGD
      derived globin gene clusters, each of which has undergone lineage-specific
      changes in gene content via repeated duplication and deletion events.
      Phylogenetic reconstructions revealed that paralogous genes convergently evolved
      similar functional properties in different teleost lineages. Consistent with
      other recent studies of globin gene family evolution in vertebrates, our results
      revealed evidence for repeated evolutionary transitions in the developmental
      regulation of Hb synthesis.

PMID- 22949524
TI  - Gene-environment interaction in preterm delivery with special reference to
      organochlorine pesticides.
AB  - We investigated the association between glutathione S-transferases mu1 (GSTM1),
      theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V
      (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs)
      level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD
      (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected
      at the time of delivery/after delivery. Women occupationally exposed to OCPs and
      other high-risk factors such as anemia, hypertension and dietary habit were
      excluded. The OCP levels were estimated by gas chromatography, and polymorphic
      analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and
      PCR-restriction fragment length polymorphism, respectively. The frequency of
      GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the
      controls. Significantly high levels of alpha-hexachlorocyclohexane (HCH), gamma
      HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal
      blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane
      and p'p'-DDE were found in the cord blood of PTD cases compared with the
      controls. A significant association was seen between beta-HCH and GSTM1 genotype
      when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and
      period of gestation (POG) was ascertained. A significant reduction in POG was
      observed. Similarly, cord blood dieldrin levels were significantly associated
      with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that
      higher levels of OCPs in pregnant women may be associated with increased risk of
      'idiopathic' PTD. Furthermore, this study shows that the interaction between high
      OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the
      risk of PTD, thus providing evidence for a gene-environment interaction in
      pregnant women.

PMID- 22949525
TI  - Solute restriction reveals an essential role for clag3-associated channels in
      malaria parasite nutrient acquisition.
AB  - The plasmodial surface anion channel (PSAC) increases erythrocyte permeability to
      many solutes in malaria but has uncertain physiological significance. We used a
      PSAC inhibitor with different efficacies against channels from two Plasmodium
      falciparum parasite lines and found concordant effects on transport and in vitro
      parasite growth when external nutrient concentrations were reduced. Linkage
      analysis using this growth inhibition phenotype in the Dd2 * HB3 genetic cross
      mapped the clag3 genomic locus, consistent with a role for two clag3 genes in
      PSAC-mediated transport. Altered inhibitor efficacy, achieved through allelic
      exchange or expression switching between the clag3 genes, indicated that the
      inhibitor kills parasites through direct action on PSAC. In a parasite unable to
      undergo expression switching, the inhibitor selected for ectopic homologous
      recombination between the clag3 genes to increase the diversity of available
      channel isoforms. Broad-spectrum inhibitors, which presumably interact with
      conserved sites on the channel, also exhibited improved efficacy with nutrient
      restriction. These findings indicate that PSAC functions in nutrient acquisition
      for intracellular parasites. Although key questions regarding the channel and its
      biological role remain, antimalarial drug development targeting PSAC should be
      pursued.

PMID- 22949527
TI  - Adding accessories for hypertension: alpha2delta-1 subunits upregulate CaV1.2
      channels in arterial myocytes in a model of genetic hypertension.

PMID- 22949526
TI  - Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK
      NCC phosphorylation cascade in hyperinsulinemic db/db mice.
AB  - Metabolic syndrome patients have insulin resistance, which causes
      hyperinsulinemia, which in turn causes aberrant increased renal sodium
      reabsorption. The precise mechanisms underlying this greater salt sensitivity of
      hyperinsulinemic patients remain unclear. Abnormal activation of the recently
      identified with-no-lysine kinase (WNK)-oxidative stress-responsive kinase 1
      (OSR1)/STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NaCl cotransporter
      (NCC) phosphorylation cascade results in the salt-sensitive hypertension of
      pseudohypoaldosteronism type II. Here, we report a study of renal WNK-OSR1/SPAK
      NCC cascade activation in the db/db mouse model of hyperinsulinemic metabolic
      syndrome. Thiazide sensitivity was increased, suggesting greater activity of NCC
      in db/db mice. In fact, increased phosphorylation of OSR1/SPAK and NCC was
      observed. In both SpakT243A/+ and Osr1T185A/+ knock-in db/db mice, which carry
      mutations that disrupt the signal from WNK kinases, increased phosphorylation of
      NCC and elevated blood pressure were completely corrected, indicating that
      phosphorylation of SPAK and OSR1 by WNK kinases is required for the increased
      activation and phosphorylation of NCC in this model. Renal phosphorylated Akt was
      increased in db/db mice, suggesting that increased NCC phosphorylation is
      regulated by the phosphatidylinositol 3-kinase/Akt signaling cascade in the
      kidney in response to hyperinsulinemia. A phosphatidylinositol 3-kinase inhibitor
      (NVP-BEZ235) corrected the increased OSR1/SPAK-NCC phosphorylation. Another more
      specific phosphatidylinositol 3-kinase inhibitor (GDC-0941) and an Akt inhibitor
      (MK-2206) also inhibited increased NCC phosphorylation. These results indicate
      that the phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK
      OSR1/SPAK-NCC phosphorylation cascade in db/db mice. This mechanism may play a
      role in the pathogenesis of salt-sensitive hypertension in human hyperinsulinemic
      conditions, such as the metabolic syndrome.

PMID- 22949528
TI  - alpha-adrenergic vasoconstriction contributes to the age-related increase in
      conduit artery retrograde and oscillatory shear.
AB  - Aging is associated with increased retrograde and oscillatory shear in peripheral
      conduit arteries of humans. Although the mechanisms responsible for these age
      related changes are not completely understood, augmented downstream alpha
      adrenergic tone likely plays a significant role in this phenomenon. Therefore, in
      protocol 1, brachial artery diameter and blood velocity were measured via Doppler
      ultrasound during (1) rest (control), (2) endogenous norepinephrine release via
      intra-arterial infusions of tyramine, and (3) alpha-adrenergic blockade via
      infusions of phentolamine in young healthy humans (n=12). Tyramine increased
      brachial artery retrograde (-4.0+/-1.4 to -9.5+/-1.4 s(-1)) and oscillatory shear
      (0.05+/-0.02 to 0.18+/-0.05 arbitrary units), whereas phentolamine abolished
      retrograde and oscillatory shear (P<0.05). Additionally, in protocol 2, we
      examined brachial artery shear patterns in young (n=12; 29+/-2 years) and older
      (n=13; 69+/-2 years) healthy adults during (1) rest (control), (2) sympathetic
      activation via lower body negative pressure, and (3) infusion of phentolamine. At
      rest, older adults exhibited greater brachial artery retrograde and oscillatory
      shear (-9.9+/-2.7 s(-1) and 0.11+/-0.03 arbitrary units, respectively) compared
      with younger adults (-3.1+/-1.0 s(-1) and 0.05+/-0.02 arbitrary units,
      respectively; P<0.05 for both). Lower body negative pressure increased retrograde
      and oscillatory shear in young (P<0.05), but not older adults (P=0.85-0.97), such
      that differences between young and older were eliminated (P>0.05). During
      infusion of phentolamine, retrograde and oscillatory shear were abolished in
      young adults (P<0.05) and markedly reduced, yet still persistent, in older adults
      (P<0.01). Our data indicate that alpha-adrenergic vasoconstriction is a major
      contributor to age-related discrepancies in conduit artery shear-rate patterns at
      rest.

PMID- 22949530
TI  - Achievement of cardiometabolic goals in aware hypertensive patients in Spain: a
      nationwide population-based study.
AB  - Despite the importance of achieving cardiometabolic goals beyond blood pressure,
      in the health of hypertensives, no comprehensive assessment of these
      characteristics has been performed in whole countries. We studied in 2008-2010 a
      total of 11 957 individuals representative of the Spanish population aged>=18
      years. Information on cardiometabolic characteristics was collected at the
      participants' homes, through structured questionnaires, physical examination, and
      fasting blood samples. A total of 3983 individuals (33.3%) had hypertension
      (>=140/90 mm Hg or current antihypertensive drug treatment), 59.4% were aware of
      their condition, 78.8% treated among those aware, and 48.5% controlled among
      those aware and treated (22.7% of all hypertensives). Of the aware hypertensives,
      13.8% had a body mass index<25 kg/m2, 38.6% consumed <2.4 g/d of sodium, 19.3%
      were diabetic with 61% attaining goal hemoglobin A1c<6.5%, whereas 42.3% had
      hypercholesterolemia, with 38.1% reaching goal low-density lipoprotein<115 mg/dL.
      Only 30.7% of overweight patients received a prescription of specific method for
      weight loss, 17.4% of daily smokers were offered a smoking cessation strategy,
      and 15.8% of older patients were given a flu shot. Aware and unaware
      hypertensives showed a similar frequency of some lifestyle, such as adequate
      physical activity. In conclusion, in a European country with a well-developed,
      free-access healthcare system, achievement of many cardiometabolic goals among
      hypertensives is poor. Moreover, a serious deficiency in hypertension awareness
      and in the effectiveness of some lifestyle interventions among aware
      hypertensives is present. Greater effort is needed in the management of
      coexisting risk factors and on lifestyle medical advice to improve the
      cardiometabolic health of hypertensives.

PMID- 22949529
TI  - G protein receptor kinase 4 polymorphisms: beta-blocker pharmacogenetics and
      treatment-related outcomes in hypertension.
AB  - G protein-coupled receptor kinases (GRKs) are important regulatory proteins for
      many G protein-coupled receptors, but little is known about GRK4
      pharmacogenetics. We hypothesized that 3 nonsynonymous GRK4 single-nucleotide
      polymorphisms, R65L (rs2960306), A142V (rs1024323), and A486V (rs1801058), would
      be associated with blood pressure response to atenolol, but not
      hydrochlorothiazide, and would be associated with long-term cardiovascular
      outcomes (all-cause death, nonfatal myocardial infarction, nonfatal stroke) in
      participants treated with an atenolol-based versus verapamil-SR-based
      antihypertensive strategy. GRK4 single-nucleotide polymorphisms were genotyped in
      768 hypertensive participants from the Pharmacogenomic Evaluation of
      Antihypertensive Responses (PEAR) trial. In whites and blacks, increasing copies
      of the variant 65L-142V haplotype were associated with significantly reduced
      atenolol-induced diastolic blood pressure lowering (-9.1+/-6.8 versus -6.8+/-7.1
      versus -5.3+/-6.4 mm Hg in participants with 0, 1, and 2 copies of 65L-142V,
      respectively; P=0.0088). One thousand four hundred sixty participants with
      hypertension and coronary artery disease from the INternational VErapamil
      SR/Trandolapril STudy (INVEST) were genotyped, and variant alleles of all 3 GRK4
      single-nucleotide polymorphisms were associated with increased risk for adverse
      cardiovascular outcomes in an additive fashion, with 486V homozygotes reaching
      statistical significance (odds ratio, 2.29 [1.48-3.55]; P=0.0002). These effects
      on adverse cardiovascular outcomes were independent of antihypertensive
      treatment. These results suggest that the presence of GRK4 variant alleles may be
      important determinants of blood pressure response to atenolol and risk for
      adverse cardiovascular events. The associations with GRK4 variant alleles were
      stronger in patients who were also ADRB1 389R homozygotes, suggesting a potential
      interaction between these 2 genes.

PMID- 22949531
TI  - Preeclampsia is associated with compromised maternal synthesis of long-chain
      polyunsaturated fatty acids, leading to offspring deficiency.
AB  - Obesity and excessive lipolysis are implicated in preeclampsia (PE). Intrauterine
      growth restriction is associated with low maternal body mass index and decreased
      lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism
      is altered in mothers in the third trimester of pregnancy with PE (n=62) or
      intrauterine growth restriction (n=23) compared with healthy pregnancies (n=164).
      Markers of lipid metabolism and erythrocyte fatty acid concentrations were
      measured. Maternal adipose tissue fatty acid composition and mRNA expression of
      adipose tissue fatty acid-metabolizing enzymes and placental fatty acid
      transporters were compared. Mothers with PE had higher plasma triglyceride (21%,
      P<0.001) and nonesterified fatty acid (50%, P<0.001) concentrations than
      controls. Concentrations of major n-6 and n-3 long-chain polyunsaturated fatty
      acids in erythrocytes were 23% to 60% lower (all P<0.005) in PE and intrauterine
      growth restriction mothers and offspring compared with controls. Subcutaneous
      adipose tissue Delta-5 and Delta-6 desaturase and very long-chain fatty acid
      elongase mRNA expression was lower in PE than controls (respectively, mean [SD]
      control 3.38 [2.96] versus PE 1.83 [1.91], P=0.030; 3.33 [2.25] versus 1.03
      [0.96], P<0.001; 0.40 [0.81] versus 0.00 [0.00], P=0.038 expression relative to
      control gene [square root]). Low maternal and fetal long-chain polyunsaturated
      fatty acid concentrations in PE may be the result of decreased maternal
      synthesis.

PMID- 22949532
TI  - Transcriptional upregulation of alpha2delta-1 elevates arterial smooth muscle
      cell voltage-dependent Ca2+ channel surface expression and cerebrovascular
      constriction in genetic hypertension.
AB  - A hallmark of hypertension is an increase in arterial myocyte voltage-dependent
      Ca2+ (CaV1.2) currents that induces pathological vasoconstriction. CaV1.2
      channels are heteromeric complexes composed of a pore-forming CaV1.2alpha1 with
      auxiliary alpha2delta and beta subunits. Molecular mechanisms that elevate CaV1.2
      currents during hypertension and the potential contribution of CaV1.2 auxiliary
      subunits are unclear. Here, we investigated the pathological significance of
      alpha2delta subunits in vasoconstriction associated with hypertension. Age
      dependent development of hypertension in spontaneously hypertensive rats was
      associated with an unequal elevation in alpha2delta-1 and CaV1.2alpha1 mRNA and
      protein in cerebral artery myocytes, with alpha2delta-1 increasing more than
      CaV1.2alpha1. Other alpha2delta isoforms did not emerge in hypertension. Myocytes
      and arteries of hypertensive spontaneously hypertensive rats displayed higher
      surface-localized alpha2delta-1 and CaV1.2alpha1 proteins, surface alpha2delta
      1:CaV1.2alpha1 ratio, CaV1.2 current density and noninactivating current, and
      pressure- and depolarization-induced vasoconstriction than those of Wistar-Kyoto
      controls. Pregabalin, an alpha2delta-1 ligand, did not alter alpha2delta-1 or
      CaV1.2alpha1 total protein but normalized alpha2delta-1 and CaV1.2alpha1 surface
      expression, surface alpha2delta-1:CaV1.2alpha1, CaV1.2 current density and
      inactivation, and vasoconstriction in myocytes and arteries of hypertensive rats
      to control levels. Genetic hypertension is associated with an elevation in
      alpha2delta-1 expression that promotes surface trafficking of CaV1.2 channels in
      cerebral artery myocytes. This leads to an increase in CaV1.2 current-density and
      a reduction in current inactivation that induces vasoconstriction. Data also
      suggest that alpha2delta-1 targeting is a novel strategy that may be used to
      reverse pathological CaV1.2 channel trafficking to induce cerebrovascular
      dilation in hypertension.

PMID- 22949533
TI  - Hemoglobin level is positively associated with blood pressure in a large cohort
      of healthy individuals.
AB  - It has been hypothesized that an increased hemoglobin level elevates blood
      pressure. The present study investigated the association between hemoglobin level
      and systolic blood pressure and diastolic blood pressure in healthy persons. The
      study population was composed of 101 377 whole blood and plasma donors, who made
      691 107 visits to the blood bank. At each visit, hemoglobin level and blood
      pressure were measured as part of the standard procedure before a blood donation.
      We used repeated measurement analysis to analyze the data. We used generalized
      estimating equation models to assess the between-person effect and linear mixed
      models to assess the within-person effect. All of the analyses were done
      separately for men and women. In the study population, 50% were men. The mean age
      in men was 49.3 years (+/-12.5 years), and in women it was 42.4 years (+/-13.7
      years). Hemoglobin level was positively associated with both systolic and
      diastolic blood pressures. With respect to the between-person effect, regression
      coefficients for systolic blood pressure were 1.3 mm Hg per millimole per liter
      increase in hemoglobin level for men and 1.8 mm Hg per millimole per liter
      increase in hemoglobin level for women. With respect to the within-person effect,
      regression coefficients for systolic blood pressure were 0.7 mm Hg and 0.9 mm Hg
      per millimole per liter increase in hemoglobin level, for men and women,
      respectively. For diastolic blood pressure, results were comparable. The results
      show that hemoglobin level is positively associated with both systolic and
      diastolic blood pressures in healthy individuals. We observed consistent effects
      between persons but also within persons.

PMID- 22949534
TI  - Aldosterone acting through the central nervous system sensitizes angiotensin II
      induced hypertension.
AB  - Previous studies have shown that preconditioning rats with a nonpressor dose of
      angiotensin II (Ang II) sensitizes the pressor response produced by later
      treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can
      modulate each other's pressor effects through actions involving the central
      nervous system. The current studies tested whether Aldo can cross-sensitize the
      pressor actions of Ang II to enhance hypertension by employing an induction-delay
      expression experimental design. Male rats were implanted for telemetered blood
      pressure recording. During induction, subpressor doses of either subcutaneous or
      intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for
      1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang
      II was given subcutaneously for 2 weeks (expression). During induction and delay,
      Aldo had no sustained effect on blood pressure. However, during expression, Ang
      II-induced hypertension was greater in the groups receiving subcutaneous or
      intracerebroventricular Aldo during induction in comparison with those groups
      receiving vehicle. Central administration of mineralocorticoid receptor
      antagonist blocked sensitization. Brain tissue collected at the end of delay and
      expression showed increased mRNA expression of several renin-angiotensin
      aldosterone system components in cardiovascular-related forebrain regions of
      cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo
      displayed greater increases in [Ca2+]i after Ang II treatment, and there was a
      greater Fra-like immunoreactivity present at the end of expression in
      cardiovascular-related forebrain structures. Taken together, these results
      indicate that Aldo pretreatment cross-sensitizes the development of Ang II
      induced hypertension probably by mechanisms that involve the central nervous
      system.

PMID- 22949536
TI  - Achievement of cardiometabolic goals in aware hypertensive patients in Spain:
      implications for population health.

PMID- 22949535
TI  - Association of genetic variation in the mitochondrial genome with blood pressure
      and metabolic traits.
AB  - Elevated blood pressure (BP) is a major risk factor for cardiovascular disease.
      Several studies have noted a consistent maternal effect on BP; consequently,
      mitochondrial DNA variation has become an additional target of investigation of
      the missing BP heritability. Analyses of common mitochondrial DNA polymorphisms,
      however, have not found evidence of association with hypertension. To explore
      associations of uncommon (frequency>5%) mitochon drial DNA variants with BP, we
      identified uncommon/rare variants through sequencing the entire mitochondrial
      genome in 32 unrelated individuals with extreme-high BP in the Framingham Heart
      Study and genotyped 40 mitochondrial single nucleotide polymorphisms in 7219
      Framingham Heart Study participants. The nonsynonymous mitochondrial single
      nucleotide polymorphism 5913G>A (Asp4Asn) in the cytochrome c oxidase subunit 1
      of respiratory complex IV demonstrated significant associations with BP and
      fasting blood glucose (FBG) levels. Individuals with the rare 5913A allele had,
      on average, 7-mm Hg higher systolic BP at baseline (Pempirical=0.05) and 17-mg/dL
      higher mean FBG over 25 years of follow-up (Pempirical=0.009). Significant
      associations with FBG levels were also detected for nonsynonymous mitochondrial
      single nucleotide polymorphism 3316G>A (Ala4Thr) in the NADH dehydrogenase
      subunit 1 of complex I. On average, individuals with rare allele 3316A had 17-
      and 25-mg/dL higher FBG at baseline (Pempirical=0.01) and over 25 years of follow
      up (Pempirical=0.007). Our findings provide the first evidence of putative
      association of variants in the mitochondrial genome with systolic BP and FBG in
      the general population. Replication in independent samples, however, is needed to
      confirm these putative associations.

PMID- 22949537
TI  - The influence of sex on early stage markers of kidney dysfunction in response to
      juvenile obesity.
AB  - Changes within the kidney in response to obesity are critical in determining the
      magnitude of later dysfunction. However, the cause of this process in response to
      juvenile onset obesity and how it can be determined by sex is poorly understood.
      We therefore examined the effect of juvenile obesity induced by exposure to a
      restricted activity environment from weaning until early adulthood on the
      molecular responses within the kidney together with glomerular area and nucleated
      cell number. This was stratified by sex and was undertaken in a sheep model of
      early obesity. Despite a similar magnitude of increase in fat mass with obesity
      onset between sexes, adverse effects on glomerular area and cell number together
      with raised gene expression within the kidney only occurred in males.
      Irrespective of obesity, gene expression of C-C motif receptor 2 was higher, and
      interleukin-6 lower, in male kidneys compared with female kidneys. The effects of
      sex on molecular differences within the kidney were amplified with obesity, which
      had no effect on any gene studied in females but had an enhanced response in
      males. Obese males therefore showed increased gene expression of a range of
      markers relating to the glucocorticoid axis, inflammation, and lipid sensing. In
      conclusion, young females were protected from adverse renal effects of obesity,
      which results in very little inflammatory or related responses. Our findings
      emphasize the critical importance of sex specificity in disease pathogenesis. An
      increased understanding of the specific mechanisms will have important
      implications for therapeutic strategies aimed at preventing adverse consequences
      of obesity.

PMID- 22949538
TI  - Insights into left ventricular remodeling through noninvasive measures of
      myocardial matrix expansion with cardiovascular magnetic resonance.

PMID- 22949540
TI  - Body fat distribution and risk of cardiovascular disease: an update.

PMID- 22949541
TI  - Implantation of the right ventricular lead of an implantable cardioverter
      defibrillator complicated by apical myocardial infarction.

PMID- 22949539
TI  - Transthyretin (TTR) cardiac amyloidosis.

PMID- 22949542
TI  - A severe restrictive aortic regurgitation resulting from valve tenting by unusual
      aortic chordae tendineae strands.

PMID- 22949545
TI  - Letter by Pettit et al regarding article, "Electrical heart activity recorded
      during prolonged avalanche burial".

PMID- 22949543
TI  - An update on the prognosis of patients with atrial fibrillation.

PMID- 22949546
TI  - First reported detection of a low pathogenicity avian influenza virus subtype H9
      infection in domestic fowl in England.
AB  - In December 2010, infection with a H9N1 low pathogenicity avian influenza (LPAI)
      virus was detected in a broiler breeder flock in East Anglia. Disease suspicion
      was based on acute drops in egg production in two of four sheds on the premises,
      poor egg shell quality and evidence of diarrhoea. H9N1 LPAI virus infection was
      confirmed by real-time reverse transcription PCR. Sequencing revealed high
      nucleotide identity of 93.6 per cent and 97.9 per cent with contemporary North
      American H9 and Eurasian N1 genes, respectively. Attempted virus isolation in
      embryonated specific pathogen free (SPF) fowls' eggs was unsuccessful.
      Epidemiological investigations were conducted to identify the source of infection
      and any onward spread. These concluded that infection was restricted to the
      affected premises, and no contacts or movements of poultry, people or fomites
      could be attributed as the source of infection. However, the infection followed a
      period of extremely cold weather and snow which impacted on the biosecurity
      protocols on site, and also led to increased wild bird activity locally,
      including waterfowl and game birds around the farm buildings. Analysis of the N1
      gene sequence suggested direct introduction from wild birds. Although H9
      infection in poultry is not notifiable, H9N2 LPAI viruses have been associated
      with production and mortality episodes in poultry in many parts of Asia and the
      Middle East. In the present H9N1 outbreak, clinical signs were relatively mild in
      the poultry with no mortality, transient impact on egg production and no
      indication of zoonotic spread. However, this first reported detection of H9 LPAI
      virus in chickens in England was also the first H9 UK poultry case for 40 years,
      and vindicates the need for continued vigilance and surveillance of avian
      influenza viruses in poultry populations.

PMID- 22949547
TI  - Prevalence of antibodies to bovine viral diarrhoea virus in bulk tank milk and
      associated risk factors in Scottish dairy herds.
AB  - Bulk tank milk samples were collected from 374 dairy farms in Scotland in
      2007/2008 along with questionnaire data relating to the management of the farm.
      Milk samples were tested for antibodies to bovine viral diarrhoea virus (BVDV)
      using a commercially available (Svanova) kit and percentage positivity scores
      calculated according to the manufacturer's guidelines. There were 220 farms that
      did not routinely vaccinate for bovine viral diarrhoea (BVD), and these were
      distributed according to the Swedish BVD eradication classes as 12.7 per cent,
      22.3 per cent, 44.5 per cent and 20.5 per cent for Classes 0, 1, 2 and 3,
      respectively. A more sophisticated statistical method (finite mixture modelling)
      which does not depend on arbitrary thresholds and categories suggested a 73 per
      cent prevalence of herds with high mean levels of antibodies. Risk factor
      analysis suggested that routine vaccination for BVD, suspicion of BVD, housing of
      pregnant cows with calves, total number of cows and the proportion of cows that
      were dry were all associated with increased BVDV antibodies in bulk milk. The
      inclusion of BVD within the farm's health plan was associated with decreased BVDV
      antibodies in the bulk milk.

PMID- 22949548
TI  - Streptococcal m1 protein triggers farnesyltransferase-dependent formation of CXC
      chemokines in alveolar macrophages and neutrophil infiltration of the lungs.
AB  - The M1 serotype of Streptococcus pyogenes plays an important role in
      streptococcal toxic shock syndrome. Simvastatin, a 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, has been shown to inhibit streptococcal
      M1 protein-induced acute lung damage, although downstream mechanisms remain
      elusive. Protein isoprenylation, such as farnesylation and geranylgeranylation,
      has been suggested to regulate anti-inflammatory effects exerted by statins.
      Here, we examined the effect of a farnesyltransferase inhibitor (FTI-277) on M1
      protein-triggered lung inflammation. Male C57BL/6 mice were treated with FTI-277
      prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were
      harvested for quantification of neutrophil recruitment, edema, and CXC chemokine
      formation. Flow cytometry was used to determine Mac-1 expression on neutrophils.
      The gene expression of CXC chemokines was determined in alveolar macrophages by
      using quantitative reverse transcription (RT)-PCR. We found that the
      administration of FTI-277 markedly decreased M1 protein-induced accumulation of
      neutrophils, edema formation, and tissue damage in the lung. Notably, inhibition
      of farnesyltransferase abolished M1 protein-evoked production of CXC chemokines
      in the lung and gene expression of CXC chemokines in alveolar macrophages.
      Moreover, FTI-277 completely inhibited chemokine-induced neutrophil migration in
      vitro. However, farnesyltransferase inhibition had no effect on M1 protein
      induced expression of Mac-1 on neutrophils. Our findings suggest that
      farnesyltransferase is a potent regulator of CXC chemokine formation in alveolar
      macrophages and that inhibition of farnesyltransferase not only reduces
      neutrophil recruitment but also attenuates acute lung injury provoked by
      streptococcal M1 protein. We conclude that farnesyltransferase activity is a
      potential target in order to attenuate acute lung damage in streptococcal
      infections.

PMID- 22949549
TI  - Subtilase cytotoxin enhances Escherichia coli survival in macrophages by
      suppression of nitric oxide production through the inhibition of NF-kappaB
      activation.
AB  - Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga
      toxigenic Escherichia coli (STEC), cleaves an endoplasmic reticulum (ER)
      chaperone, BiP/Grp78, leading to induction of ER stress and caspase-dependent
      apoptosis. SubAB alters the innate immune response. SubAB pretreatment of
      macrophages inhibited lipopolysaccharide (LPS)-induced production of both
      monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor alpha (TNF
      alpha). We investigated here the mechanism by which SubAB inhibits nitric oxide
      (NO) production by mouse macrophages. SubAB suppressed LPS-induced NO production
      through inhibition of inducible NO synthase (iNOS) mRNA and protein expression.
      Further, SubAB inhibited LPS-induced IkappaB-alpha phosphorylation and nuclear
      localization of the nuclear factor-kappaB (NF-kappaB) p65/p50 heterodimer.
      Reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that SubAB
      reduced LPS-induced NF-kappaB p65/p50 heterodimer binding to an NF-kappaB binding
      site on the iNOS promoter. In contrast to the native toxin, a catalytically
      inactivated SubAB mutant slightly enhanced LPS-induced iNOS expression and
      binding of NF-kappaB subunits to the iNOS promoter. The SubAB effect on LPS
      induced iNOS expression was significantly reduced in macrophages from NF-kappaB1
      (p50)-deficient mice, which lacked a DNA-binding subunit of the p65/p50
      heterodimer, suggesting that p50 was involved in SubAB-mediated inhibition of
      iNOS expression. Treatment of macrophages with an NOS inhibitor or expression of
      SubAB by E. coli increased E. coli survival in macrophages, suggesting that NO
      generated by macrophages resulted in efficient killing of the bacteria and SubAB
      contributed to E. coli survival in macrophages. Thus, we hypothesize that SubAB
      might represent a novel bacterial strategy to circumvent host defense during STEC
      infection.

PMID- 22949550
TI  - CsrRS and environmental pH regulate group B streptococcus adherence to human
      epithelial cells and extracellular matrix.
AB  - Streptococcus agalactiae (group B Streptococcus or GBS) is a common colonizer of
      the gastrointestinal and genital tracts and an important cause of invasive
      infections in newborn infants and in adults with predisposing chronic conditions
      or advanced age. Attachment to epithelial surfaces at mucosal sites is a critical
      step in the successful colonization of a human host, and regulation of this
      process is likely to play an important role in both commensalism and
      dissemination to cause invasive disease. We found that inactivation of the CsrRS
      (or CovRS) two-component system increased GBS adherence to epithelial cells
      derived from human vaginal, cervical, and respiratory epithelium, as well as
      increasing adherence to extracellular matrix proteins and increasing biofilm
      formation on polystyrene. Neutral (as opposed to acidic) pH enhanced GBS binding
      to vaginal epithelial cells and to fibrinogen and fibronectin, effects that were
      partially dependent on CsrRS. The regulatory effects of CsrRS and environmental
      pH on bacterial adherence correlated with their effects on the expression of
      multiple surface adhesins, as assessed by quantitative reverse transcription-PCR.
      We conclude that GBS adherence to epithelial and abiotic surfaces is regulated by
      the CsrRS two-component system and by environmental pH through their regulatory
      effects on the expression of bacterial surface adhesins. Dynamic regulation of
      GBS adherence enhances the organism's adaptability to survival in multiple niches
      in the human host.

PMID- 22949551
TI  - Structural and functional properties of staphylococcal superantigen-like protein
      4.
AB  - Staphylococcus aureus is a prevalent and significant human pathogen. Among the
      repertoire of virulence factors produced by this bacterium are the 14
      staphylococcal superantigen-like (SSL) proteins. SSL protein 4 (SSL4) is one
      member of this family and contains a highly conserved carbohydrate binding site
      also found in SSL2, SSL3, SSL5, SSL6, and SSL11. Recombinant SSL4(t), comprising
      amino acids 109 to 309 of Newman strain SSL4 (SSL4-Newman), has been shown to
      bind and be internalized by human granulocytes and macrophages in a sialic-acid
      (Sia)-dependent manner. SSL4(t) can compete with itself for cell binding,
      indicating that binding is target specific. A 2.5-A-resolution crystal structure
      of SSL4(t) complexed with sialyl Lewis X (sLe(x)) [sLe(x)-Neu5Acalpha2-3Galbeta1
      4(Fucalpha1-3)GlcNAc] revealed a similar binding site to SSL5 and SSL11. These
      data, along with data on SSL4(t) binding to a glycan array and biosensor analysis
      of sLe(x) and sialyllactosamine (sLacNac) binding are compared with those for
      SSL11. Although these proteins show great similarity in their carbohydrate
      binding sites, with a root mean square (RMS) difference between main chain atom
      positions of only 0.34 A, these proteins differ in detail in their affinity for
      sLe(x) and sLacNac, as well as their glycan preference. Together with cell
      binding data, this shows how S. aureus produces multiple related proteins that
      target myeloid cells through specific sialyllactosamine-containing glycoproteins.

PMID- 22949552
TI  - Pseudomonas aeruginosa Alkyl quinolones repress hypoxia-inducible factor 1 (HIF
      1) signaling through HIF-1alpha degradation.
AB  - The transcription factor hypoxia-inducible factor 1 (HIF-1) has recently emerged
      to be a crucial regulator of the immune response following pathogen perception,
      including the response to the important human pathogen Pseudomonas aeruginosa.
      However, as mechanisms involved in HIF-1 activation by bacterial pathogens are
      not fully characterized, understanding how bacteria and bacterial compounds
      impact on HIF-1alpha stabilization remains a major challenge. In this context, we
      have focused on the effect of secreted factors of P. aeruginosa on HIF-1
      regulation. Surprisingly, we found that P. aeruginosa cell-free supernatant
      significantly repressed HIF-1alpha protein levels. Further characterization
      revealed that HIF-1alpha downregulation was dependent on a subset of key secreted
      factors involved in P. aeruginosa pathogenesis, the 2-alkyl-4-quinolone (AQ)
      quorum sensing (QS) signaling molecules, and in particular the pseudomonas
      quinolone signal (PQS). Under hypoxic conditions, the AQ-dependent downregulation
      of HIF-1alpha was linked to the suppressed induction of the important HIF-1
      target gene hexokinase II. Furthermore, we demonstrated that AQ molecules
      directly target HIF-1alpha protein degradation through the 26S-proteasome
      proteolytic pathway but independently of the prolyl hydroxylase domain (PHD). In
      conclusion, this is the first report showing that bacterial molecules can repress
      HIF-1alpha protein levels. Manipulation of HIF-1 signaling by P. aeruginosa AQs
      could have major consequences for the host response to infection and may
      facilitate the infective properties of this pathogen.

PMID- 22949553
TI  - Lack of lipid A pyrophosphorylation and functional lptA reduces inflammation by
      Neisseria commensals.
AB  - The interaction of the immune system with Neisseria commensals remains poorly
      understood. We have previously shown that phosphoethanolamine on the lipid A
      portion of lipooligosaccharide (LOS) plays an important role in Toll-like
      receptor 4 (TLR4) signaling. For pathogenic Neisseria, phosphoethanolamine is
      added to lipid A by the phosphoethanolamine transferase specific for lipid A,
      which is encoded by lptA. Here, we report that Southern hybridizations and
      bioinformatics analyses of genomic sequences from all eight commensal Neisseria
      species confirmed that lptA was absent in 15 of 17 strains examined but was
      present in N. lactamica. Mass spectrometry of lipid A and intact LOS revealed the
      lack of both pyrophosphorylation and phosphoethanolaminylation in lipid A of
      commensal species lacking lptA. Inflammatory signaling in human THP-1 monocytic
      cells was much greater with pathogenic than with commensal Neisseria strains that
      lacked lptA, and greater sensitivity to polymyxin B was consistent with the
      absence of phosphoethanolamine. Unlike the other commensals, whole bacteria of
      two N. lactamica commensal strains had low inflammatory potential, whereas their
      lipid A had high-level pyrophosphorylation and phosphoethanolaminylation and
      induced high-level inflammatory signaling, supporting previous studies indicating
      that this species uses mechanisms other than altering lipid A to support
      commensalism. A meningococcal lptA deletion mutant had reduced inflammatory
      potential, further illustrating the importance of lipid A pyrophosphorylation and
      phosphoethanolaminylation in the bioactivity of LOS. Overall, our results
      indicate that lack of pyrophosphorylation and phosphoethanolaminylation of lipid
      A contributes to the immune privilege of most commensal Neisseria strains by
      reducing the inflammatory potential of LOS.

PMID- 22949554
TI  - Capsular polysaccharide of Erysipelothrix rhusiopathiae, the causative agent of
      swine erysipelas, and its modification with phosphorylcholine.
AB  - The capsule has been implicated in the virulence of the swine pathogen
      Erysipelothrix rhusiopathiae, a rod-shaped, intracellular Gram-positive bacterium
      that has a unique phylogenetic position in the phylum Firmicutes and is a close
      relative of Mollicutes (mycoplasma species). In this study, we analyzed the
      genetic locus and composition of the capsular polysaccharide (CPS) of the
      Fujisawa strain of E. rhusiopathiae. Genome analysis of the Fujisawa strain
      revealed that the genetic locus for capsular polysaccharide synthesis (cps) is
      located next to an lic operon, which is involved in the incorporation and
      expression of phosphorylcholine (PCho). Reverse transcription-PCR analysis showed
      that cps and lic are transcribed as a single mRNA, indicating that the loci form
      an operon. Using the cell surface antigen-specific monoclonal antibody (MAb) ER21
      as a probe, the capsular materials were isolated from the Fujisawa strain by hot
      water extraction and treatment with DNase, RNase, pronase, and N-acetylmuramidase
      SG, followed by anion-exchange and gel filtration chromatography. The materials
      were then analyzed by high-performance liquid chromatography, mass spectrometry,
      and nuclear magnetic resonance (NMR) spectroscopy. The CPS of E. rhusiopathiae is
      heterogeneous and consists of the major monosaccharides galacturonic acid,
      galactose, mannose, glucose, arabinose, xylose, and N-acetylglucosamine and some
      minor monosaccharides containing ribose, rhamnose, and N-acetylgalactosamine. In
      addition, the capsule is modified by PCho, which comigrates with the capsular
      materials, as determined by Western immunoblotting, and colocalizes on the cell
      surface, as determined by immunogold electron microscopy. Virulence testing of
      PCho-defective mutants in mice demonstrated that PCho is critical for the
      virulence of this organism.

PMID- 22949555
TI  - The meningococcal adhesin NhhA provokes proinflammatory responses in macrophages
      via toll-like receptor 4-dependent and -independent pathways.
AB  - Activation of macrophages by Toll-like receptors (TLRs) and functionally related
      proteins is essential for host defense and innate immunity. TLRs recognize a wide
      variety of pathogen-associated molecules. Here, we demonstrate that the
      meningococcal outer membrane protein NhhA has immunostimulatory functions and
      triggers release of proinflammatory cytokines from macrophages. NhhA-induced
      cytokine release was found to proceed via two distinct pathways in RAW 264.7
      macrophages. Interleukin-6 (IL-6) secretion was dependent on activation of TLR4
      and required the TLR signaling adaptor protein MyD88. In contrast, release of
      tumor necrosis factor (TNF) was TLR4 and MyD88 independent. Both pathways
      involved NF-kappaB-dependent gene regulation. Using a PCR-based screen, we could
      identify additional targets of NhhA-dependent gene activation such as the
      cytokines and growth factors IL-1alpha, IL-1beta, granulocyte colony-stimulating
      factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In
      human monocyte-derived macrophages, G-CSF, GM-CSF, and IL-6 were found to be
      major targets of NhhA-dependent gene regulation. NhhA induced transcription of IL
      6 and G-CSF mRNA via TLR4-dependent pathways, whereas GM-CSF transcription was
      induced via TLR4-independent pathways. These data provide new insights into the
      role of NhhA in host-pathogen interaction.

PMID- 22949558
TI  - The costs of choice in senior care.

PMID- 22949556
TI  - Construction and evaluation of a novel recombinant T cell epitope-based vaccine
      against Coccidioidomycosis.
AB  - Clinical and animal studies of coccidioidomycosis have demonstrated that
      activated CD4(+) T lymphocytes are essential for protection against this fungal
      respiratory disease. We previously reported a vaccine against Coccidioides
      infection which contained three recombinant CD4(+) T cell-reactive proteins and
      induced a robust, protective immune response in mice. Due to the anticipated high
      cost of production and clinical assessment of this multivalent vaccine, we
      generated a single protein which contained immunodominant T cell epitopes of the
      three polypeptides. Epitopes were initially identified by computational
      prediction of their ability to bind promiscuously to human major
      histocompatibility complex class II (MHC II) molecules. Cellular immunoassays
      confirmed the immunogenicity of the synthesized epitope peptides, while in vitro
      binding assays revealed a range of peptide affinity for MHC II. A DNA construct
      was synthesized for bacterial expression of a recombinant protein vaccine which
      contained five epitopes with the highest affinity for human MHC II, each fused
      with leader and spacer peptides proposed to optimize epitope processing and
      presentation to T cell receptors. Recall assays of immune T lymphocytes obtained
      from human MHC II-expressing HLA-DR4 transgenic mice confirmed that 4 of the 5
      epitope peptides were processed. Mice immunized with the epitope-based vaccine
      admixed with a synthetic oligodeoxynucleotide adjuvant or loaded into yeast
      glucan particles and then challenged intranasally with Coccidioides showed early
      lung infiltration of activated T helper-1 (Th1), Th2, and Th17 cells, elevated
      gamma interferon (IFN-gamma) and interleukin (IL)-17 production, significant
      reduction of fungal burden, and prolongation of survival compared to
      nonvaccinated mice. This is the first report of an epitope-based vaccine against
      coccidioidomycosis.

PMID- 22949559
TI  - Attracting small-town docs a challenge.

PMID- 22949560
TI  - The new rules of naturopathy.

PMID- 22949561
TI  - Aboriginal health programming under siege, critics charge.

PMID- 22949562
TI  - Psoriasis.

PMID- 22949563
TI  - Effect of a centralized prescription network on inappropriate prescriptions for
      opioid analgesics and benzodiazepines.
AB  - BACKGROUND: Opioid analgesics and benzodiazepines are often misused in clinical
      practice. We determined whether implementation of a centralized prescription
      network offering real-time access to patient-level data on filled prescriptions
      (PharmaNet) reduced the number of potentially inappropriate prescriptions for
      opioids and benzodiazepines. METHODS: We conducted a time series analysis using
      prescription records between Jan. 1, 1993, and Dec. 31, 1997, for residents of
      the province of British Columbia who were receiving social assistance or were 65
      years or older. We calculated monthly percentages of filled prescriptions for an
      opioid or a benzodiazepine that were deemed inappropriate (those issued by a
      different physician and dispensed at a different pharmacy within 7 days after a
      filled prescription of at least 30 tablets of the same drug). RESULTS: Within 6
      months after implementation of PharmaNet in July 1995, we observed a relative
      reduction in inappropriate filled prescriptions for opioids of 32.8% (95%
      confidence interval [CI] 31.0%-34.7%) among patients receiving social assistance;
      inappropriate filled prescriptions for benzodiazepines decreased by 48.6% (95% CI
      43.2%-53.1%). Similar and statistically significant reductions were observed
      among residents 65 years or older. INTERPRETATION: The implementation of a
      centralized prescription network was associated with a dramatic reduction in
      inappropriate filled prescriptions for opioids and benzodiazepines.

PMID- 22949564
TI  - Intracranial abscess as a complication of nasal septal abscess.

PMID- 22949566
TI  - Extended cleavage specificity of the mast cell chymase from the crab-eating
      macaque (Macaca fascicularis): an interesting animal model for the analysis of
      the function of the human mast cell chymase.
AB  - Serine proteases are the major protein constituents within mast cell secretory
      granules. These proteases are subdivided into chymases and tryptases depending on
      their primary cleavage specificity. Here, we present the extended cleavage
      specificity of the macaque mast cell chymase and compare the specificity with
      human chymase (HC) and dog chymase (DC) that were produced in the same insect
      cell expression host. The macaque chymase (MC) shows almost identical
      characteristics as the HC, including both primary and extended cleavage
      specificities as well as sensitivity to protease inhibitors, whereas the DC
      differs in several of these characteristics. Although previous studies have shown
      that mouse mast cell protease-4 (mMCP-4) is similar in its hydrolytic specificity
      to the HC, mouse mast cells contain several related enzymes. Thus mice may not be
      the most appropriate model organism for studying HC activity and inhibition.
      Importantly, macaques express only one chymase and, as primates, are closely
      related to human general physiology. In addition, the human and macaque enzymes
      both cleave angiotensin I (Ang I) in the same way, generating primarily
      angiotensin II (Ang II) and they do not further degrade the peptide like most
      rodent enzymes do. Both enzymes also cleave two additional potential in vivo
      substrates, fibronectin and secretory leukocyte protease inhibitor (SLPI) in a
      similar way. Given the fact that both HC and MC are encoded by a single gene with
      high sequence homology and that many physiological processes are similar between
      these species, the macaque may be a very interesting model to study the
      physiological role of the chymase and to determine the potency and potential side
      effects of various chymase inhibitors designed for therapeutic human use.

PMID- 22949567
TI  - Nitric oxide and glucocorticoids synergize in inducing apoptosis of CD4+8+
      thymocytes: implications for 'Death by Neglect' and T-cell function.
AB  - Thymic epithelial cells (TECs) play a central role in T-cell development by
      presenting self-antigens on MHC proteins. Double-positive (DP) thymocytes that
      fail to interact with TEC via their TCR die by 'Death by Neglect'. We
      demonstrated a role for TEC-derived glucocorticoids (GCs) in this process. In a
      previous study, we used an in vitro system recapitulating Death by Neglect, to
      demonstrate the involvement of nitric oxide (NO) and inducible NO synthase (iNOS)
      in this process. In this study, we show that NO synergizes with GCs to induce
      apoptosis of DP thymocytes in a fetal thymic organ culture. Also, DP thymocytes
      from iNOS-/- mice are less sensitive to GC-induced apoptosis. Furthermore, the
      number of DP thymocytes in iNOS-/- mice is higher than in wild-type mice,
      suggesting a role for NO in Death by Neglect. This phenomenon effects T-cell
      function profoundly: iNOS-/- T cells do not respond to TCR-mediated activation
      signals, measured by up-regulation of CD69, IL-2R and IFNgamma secretion. This
      failure to activate is a result of TCR incompetence because iNO-/- T cells
      respond to TCR-independent stimuli (phorbol myristate acetate and calcium
      ionophore). This study suggests that NO and GCs synergize to execute TEC-induced
      death of DP thymocytes.

PMID- 22949568
TI  - Mechanisms modulating immune clearance during human cytomegalovirus latency.

PMID- 22949569
TI  - Effectiveness of antismoking media messages and education among adolescents in
      Malaysia and Thailand: findings from the international tobacco control southeast
      Asia project.
AB  - INTRODUCTION: Finding ways to discourage adolescents from taking up smoking is
      important because those who begin smoking at an earlier age are more likely to
      become addicted and have greater difficulty in quitting. This article examined
      whether anti smoking messages and education could help to reduce smoking
      susceptibility among adolescents in two Southeast Asian countries and to explore
      the possible moderating effect of country and gender. METHODS: Data came from
      Wave 1 of the International Tobacco Control Southeast Asia Project (ITC-SEA)
      survey conducted in Malaysia (n = 1,008) and Thailand (n = 1,000) where
      adolescents were asked about receiving antismoking advice from nurses or doctors,
      being taught at schools about the danger of smoking, noticing antismoking
      messages, knowledge of health effects of smoking, beliefs about the health risks
      of smoking, smoking susceptibility, and demographic information. Data were
      analyzed using chi-square tests and logistic regression models. RESULTS: Overall,
      significantly more Thai adolescents reported receiving advice from their nurses
      or doctors about the danger of smoking (p < .001), but no country difference was
      observed for reported antismoking education in schools and exposure to
      antismoking messages. Multivariate analyses revealed that only provision of
      antismoking education at schools was significantly associated with reduced
      susceptibility to smoking among female Malaysian adolescents (OR = 0.26). Higher
      knowledge of smoking harm and higher perceived health risk of smoking were
      associated with reduced smoking susceptibility among Thai female (OR = 0.52) and
      Malaysian male adolescents (OR = 0.63), respectively. CONCLUSIONS: Educating
      adolescents about the dangers of smoking in schools appears to be the most
      effective means of reducing adolescents' smoking susceptibility in both
      countries, although different prevention strategies may be necessary to ensure
      effectiveness for male and female adolescents.

PMID- 22949570
TI  - Perceived treatment assignment and smoking cessation in a clinical trial of
      bupropion versus placebo.
AB  - INTRODUCTION: Psychoactive effects of smoking cessation medi cations such as
      bupropion may allow participants in smoking cessation clinical trials to
      correctly guess their treatment assignment at rates greater than chance. Previous
      research has found an association between perceived treatment assignment and
      smoking cessation rates among moderate to heavy smokers (>= 10 cigarettes per day
      [cpd]) in two bupropion clinical trials. METHODS: The aim of this study was to
      determine the impact of perceived treatment assignment on end-of-treatment
      cotinine-verified smoking abstinence at Week 7 and Week 26 among African American
      light smokers (<= 10 cpd) enrolled in a double-blind, placebo-controlled study of
      bupropion. Participants (n = 390) included in this study reported their perceived
      treatment assignment on the end-of-treatment (Week 7) survey. RESULTS:
      Participants were predominantly female (63.1%), 48.1 years of age (SD = 11.2),
      and smoked an average of 8 cpd (SD = 2.5). Participants given bupropion were more
      likely to correctly guess their treatment assignment (69%; 140/203) than those
      assigned to placebo (51.3%; 96/187) (p < .0001). After adjusting for treatment
      condition, participants who perceived assignment to bupropion versus placebo were
      not more likely to be abstinent than those who perceived assignment to placebo at
      Week 7 or at Week 26. The interaction between treatment and perceived treatment
      assignment was also nonsignificant. CONCLUSIONS: Consistent with two previous
      studies testing bupropion, participants assigned to bupropion were more likely to
      correctly guess their treatment assignment than those assigned to placebo.
      However, in contrast to previous studies with heavier smokers, perceived
      treatment assignment did not significantly impact cotinine-verified abstinence in
      light smokers.

PMID- 22949571
TI  - Tobacco industry strategies to minimize or mask cigarette smoke: opportunities
      for tobacco product regulation.
AB  - INTRODUCTION: The tobacco industry has developed technologies to reduce the
      aversive qualities of cigarette smoke, including secondhand smoke (SHS). While
      these product design changes may lessen concerns about SHS, they may not reduce
      health risks associated with SHS exposure. Tobacco industry patents were reviewed
      to understand recent industry strategies to mask or minimize cigarette smoke from
      traditional cigarettes. METHODS: Patent records published between 1997 and 2008
      that related to cigarette smoke were conducted using key word searches. The U.S.
      Patent and Trademark Office web site was used to obtain patent awards, and the
      World Intellectual Property Organization's Patentscope and Free Patents Online
      web sites were used to search international patents. RESULTS: The search
      identified 106 relevant patents published by Japan Tobacco Incorporated, British
      America Tobacco, Philip Morris International, and other tobacco manufacturers or
      suppliers. The patents were classified by their intended purpose, including
      reduced smoke constituents or quantity of smoke emitted by cigarettes (58%, n =
      62), improved smoke odor (25%, n = 26), and reduced visibility of smoke (16%, n =
      18). Innovations used a variety of strategies including trapping or filtering
      smoke constituents, chemically converting gases, adding perfumes, or altering
      paper to improve combustion. CONCLUSIONS: The tobacco industry continues to
      research and develop strategies to reduce perceptions of cigarette smoke,
      including the use of additives to improve smoke odor. Surveillance and regulatory
      response to industry strategies to reduce perceptions of SHS should be
      implemented to ensure that the public health is adequately protected.

PMID- 22949572
TI  - Initial reactions to tobacco use and risk of future regular use.
AB  - INTRODUCTION: Studies suggest that initial smoking pleasure influences future
      smoking behavior. We investigated how initial reactions to cigarettes or Swedish
      smokeless tobacco (snus) were associated with future use among 10,708 adults from
      the Swedish Twin Registry. METHODS: The Early Smoking Experience questionnaire
      captured physiologic reactions to initial tobacco use. Binary recursive
      partitioning (BRP) identified combinations of initial reactions predictive of
      regular tobacco use. Analyses, stratified by sex, were conducted separately among
      those who experimented with only cigarettes (EC), only snus (ES), and both
      products (EC+S). RESULTS: Among EC, 39.8% of men and 43.7% of women became
      smokers, while among ES, 78.6% of men and 53.7% of women became snus users. Among
      EC+S, 31.3% of men and 20.0% of women became dual users. BRP identified different
      reactions as predictive of future smoking for men (buzz) and women (dizziness,
      difficulty inhaling). No initial reaction predicted future snus use among men,
      but pleasant sensations, later age at first use, and relaxation predicted future
      snus use for women. Among EC+S, future exclusive use of either product was
      associated with a favorable initial reaction to that product. Dual users
      experienced higher prevalence of pleasant reactions and lower prevalence of
      unpleasant reactions in response to both products. CONCLUSIONS: Our findings
      support that those who progress to regular tobacco use may be sensitive to the
      rewarding effects of nicotine but suggest that initial reactions differ by
      tobacco type. A high proportion of men became regular snus users regardless of
      initial reactions.

PMID- 22949573
TI  - Tobacco use among southwestern Alaska Native people.
AB  - INTRODUCTION: We examined the characteristics, attitudes, beliefs, and exposure
      to tobacco products in a cohort of rural dwelling Alaska Native (AN) people.
      METHODS: We conducted a study of 400 of AN adult tobacco  users and nonusers
      living in Southwestern Alaska. Questionnaires covered variables such as
      demographics, tobacco-use history, current tobacco use and dependence scales,
      general health status, attitudes and beliefs about tobacco, and quitting history.
      RESULTS: The study population smoked 7.8 cigarettes per day compared with 16.8 on
      average for the U.S. population: a significant proportion of the population
      engaged in dual use of cigarettes and smokeless tobacco products. Over one third
      (40.9%), first tried tobacco at age 11 or younger. The mean measures of tobacco
      addiction (e.g., Fagerstrom Test for Nicotine Dependence, Severson Scale of
      Smokeless Tobacco Dependence) scores were lower compared with other U.S.
      populations. CONCLUSIONS: Very high tobacco-use prevalence, dual product use, and
      early tobacco use are observed in Southwestern AN people. Unexpectedly these did
      not appear to be correlated with heavier individual tobacco use or higher levels
      of addiction in this population.

PMID- 22949575
TI  - Effects of moderating factors including serotonin transporter polymorphisms on
      smoking behavior: a systematic review and meta-analysis update.
AB  - INTRODUCTION: The aim of this review was to report an update of a previous meta
      analysis (by another group) of a possible relationship between serotonin
      transporter (5-HTTLPR) genotype and smoking behavior, and extend previous work by
      factoring in some demographic parameters (age, gender, and ethnicity) in a
      multiple regression model to examine the relationship between these demographic
      factors and the effect of 5-HTTLPR polymorphism on smoking behavior. METHODS:
      Effect sizes were calculated for each study selected for meta-analysis and were
      pooled using the random-effects model, which assumes within-study sampling and
      between-study variance and provides wider confidence intervals. Effect sizes
      calculated in each study were used to evaluate the correlations with participant
      data for age, gender, and ethnicity (moderating variable) by multiple regression
      analysis. RESULTS: Meta-analysis indicated a relationship between smoking rate
      and the 5-HTTLPR genotype, but not smoking initiation and persistence, which was
      consistent with that of the previous review. Publication bias was not indicated
      for smoking initiation or persistence. Multiple regression analysis revealed that
      mean participant age significantly affected effect sizes for smoking initiation
      and persistence of each study. The proportion of Caucasians may have been
      partially influenced by the difference in effect sizes for smoking persistence
      among the studies. CONCLUSION: A significant relationship stratified by ancestry
      was observed between the 5-HTTLPR genotype and smoking rate, but not between the
      5-HTTLPR genotype and smoking initiation and persistence. Regression analysis
      detected effects of age and/or ethnicity as moderating factors on smoking
      initiation and persistence.

PMID- 22949574
TI  - Does tobacco-control mass media campaign exposure prevent relapse among recent
      quitters?
AB  - OBJECTIVE: To determine whether greater mass media campaign exposure may assist
      recent quitters to avoid relapse. METHOD: Using date of data collection and
      postcode, media market estimates of televised tobacco-control advertising
      exposure measured by gross ratings points (GRPs) were merged with a replenished
      cohort study of 443 Australians who had quit in the past year. Participants'
      demographic and smoking characteristics prior to quitting, and advertising
      exposure in the period after quitting, were used to predict relapse 1 year later.
      RESULTS: In multivariate analysis, each increase in exposure of 100 GRPs (i.e., 1
      anti-smoking advertisement) in the three-month period after the baseline quit was
      associated with a 5% increase in the odds of not smoking at follow-up (OR = 1.05,
      95% CI 1.02-1.07, p < 0.001). This relationship was linear and unmodified by
      length of time quit prior to the baseline interview. At the mean value of 1081
      GRPs in the 3 months after the baseline-quit interview, the predicted probability
      of being quit at follow-up was 52%, whereas it was 41% for the minimum (0) and
      74% for the maximum (3,541) GRPs. CONCLUSION: Greater exposure to tobacco-control
      mass media campaigns may reduce the likelihood of relapse among recent quitters.

PMID- 22949576
TI  - Crossing the smoking divide for young adults: expressions of stigma and identity
      among smokers and nonsmokers.
AB  - OBJECTIVES: Denormalizing campaigns reframe smoking as an unappealing behavior,
      more likely to lead to social exclusion than inclusion. Social identity theory
      suggests this strategy will reinforce smoke-free norms and, as these become
      mainstream, decrease smoking prevalence. However, little is known about how these
      campaigns affect perceptions of smoking among young adult smokers and nonsmokers,
      or behavior toward smokers. A qualitative study was conducted to a) explore how
      smokers and smoking were perceived in an environment where smoking has become an
      increasingly unacceptable social behavior and b) examine whether and how this
      environment stigmatized smokers. METHODS: About 14 group discussions and 4 in
      depth interviews involving 86 participants, aged between 18 and 24 and of Maori,
      Pacific, and NZ European ethnicities, were conducted as part of a wider study
      examining young adults' responses to tobacco branding and plain packaging.
      RESULTS: The themes identified illustrated how nonsmokers' perception of smoking
      as illogical and self-destructive supported harsh reactions, including
      stigmatizing behaviors that antagonized smokers. Nonsmokers, who recognized
      smoking's addictiveness, were more empathic and less judgmental of smokers.
      CONCLUSION: Including empathic content in smoking denormalizing campaigns may
      reduce judgmental reactions that inadvertently create a gulf between status of
      young adult smokers and nonsmokers. A supportive/empathic tobacco-control
      denormalization approach could enhance young adult smokers' willingness to make
      the transition from smoker to smoke free and elicit stronger support for their
      efforts from nonsmokers.

PMID- 22949577
TI  - Preliminary evidence that adherence to counseling mediates the effects of
      pretreatment self-efficacy and motivation on outcome of a cessation attempt in
      smokers with ADHD.
AB  - BACKGROUND: Few studies have evaluated predictors of smoking cessation outcomes
      in smokers with attention-deficit/hyperactivity disorder (ADHD), which could help
      to improve suboptimal treatment outcomes in this population. The purpose of this
      study was to examine pretreatment thoughts about smoking abstinence (i.e., desire
      to quit, perceived difficulty quitting, and expected success in quitting) as
      predictors of smoking cessation outcomes in smokers with ADHD and to determine
      the extent to which treatment adherence mediates these relationships. METHODS:
      Participants were adult smokers with ADHD (n = 255), who were enrolled in a
      multisite smoking cessation study and received either osmotic-release oral system
      methylphenidate (OROS-MPH) or placebo in combination with transdermal nicotine
      replacement and brief cessation counseling. Bootstrapped logistic regression
      models were generated to test main effects of thoughts about abstinence on
      smoking cessation outcomes and to examine treatment adherence as a mediator of
      these relationships. RESULTS: Desire to quit and expected success in quitting,
      but not perceived difficulty quitting, predicted smoking cessation outcomes, as
      did all of the treatment adherence variables (i.e., percent sessions attended,
      counselor ratings of counseling adherence, and percent patch adherence).
      Counseling adherence partially mediated the relationship between smoking
      cessation outcomes and both pretreatment desire to quit and expected success.
      CONCLUSIONS: Smokers with ADHD who have higher self-efficacy (i.e., expected
      success) and motivation (i.e., desire) to quit are more adherent to smoking
      cessation counseling and have better smoking cessation outcomes. Additional
      research is needed to determine whether treatment-seeking smokers with ADHD would
      benefit from an intervention designed to increase self-efficacy and motivation to
      quit.

PMID- 22949578
TI  - Effects of smoking cues and argument strength of antismoking advertisements on
      former smokers' self-efficacy, attitude, and intention to refrain from smoking.
AB  - INTRODUCTION: This study examines the impact of smoking cues employed in
      antismoking advertisements on former smokers. Previous findings indicate that
      visual smoking cues in antismoking advertisements with weak antismoking arguments
      can elicit smoking urges in smokers and undermine message effectiveness. This
      study extends these observations to former smokers asking whether smoking cues in
      antismoking advertisements influence former smokers' self-efficacy, attitudes,
      and intention to refrain from smoking, along with smoking urges and perceived
      message effectiveness. METHODS: The study was a mixed 2 (smoking cues; present
      vs. absent) * 2 (argument strength [AS]; high vs. low) design where smoking cue
      was a between-subject factor and AS was a within-subject factor. Potential
      participants recruited via online ads were screened in a phone interview for
      their eligibility. A total of 105 former smokers (aged 21-65) participated in the
      study, which was conducted in a laboratory setting. Repeated measure ANOVA and
      MANOVA were used for the analyses. RESULTS: The results showed that the presence
      of smoking cues in antismoking ads undermines former smokers' behavioral self
      efficacy, attitude, and intention about smoking abstinence, which increased as AS
      for the ads increased. Former smokers' reports of smoking urge were not affected
      by smoking cues or AS. However, consistent with previous findings for smokers,
      the presence of cues weakened perceived message effectiveness of antismoking ads
      rated by former smokers. CONCLUSIONS: The effect of smoking cues on former
      smokers' self-efficacy, attitude, and intention to refrain from smoking is
      problematic. Inclusion of smoking cues in antismoking ads should be undertaken
      only when accompanied by strong arguments.

PMID- 22949579
TI  - Psychological differences between smokers who spontaneously quit during pregnancy
      and those who do not: a review of observational studies and directions for future
      research.
AB  - INTRODUCTION: Although remarkable interindividual differences among pregnant
      smokers' decision/ability to quit have been documented, the psychological factors
      that may account for these differences have received less attention and comprised
      the primary aim of this review. METHODS: We searched the medical and behavioral
      sciences literature from 1996 to November 2011 using PubMed and PsycINFO((r)).
      Fifty-one articles were identified based on titles or abstracts. These articles
      were reviewed in full and searched for quantitative observational studies of
      population-based or clinical samples, with the main topic of comparing smokers
      who quit spontaneously during pregnancy with those who did not, utilizing
      multivariable analyses. RESULTS: The eight pertinent studies reviewed herein
      included four longitudinal studies and four cross-sectional analyses. Amidst
      significant variability among measures used, social support, depressive symptoms,
      and anxiety appeared unrelated to smoking cessation during pregnancy.
      Furthermore, when severity of nicotine dependence was controlled, maternal
      history of attention-deficit/hyperactivity disorder, depression, bipolar
      disorder, and schizophrenia all showed no independent relationship with smoking
      cessation during pregnancy, whereas maternal history of conduct disorder did.
      Secure attachment, prosocial personality, self-esteem, and perceived parenting
      competence were additional predictors of cessation during pregnancy. CONCLUSIONS:
      A greater understanding of psychological factors that differentiate smokers who
      spontaneously quit during pregnancy from those who do not is crucial to the
      design of more effective prenatal smoking cessation interventions and also may
      elucidate causal mechanisms that underlie the well-established link between
      maternal smoking during pregnancy and offspring behavioral problems. Directions
      for future research and public health and policy implications are discussed.

PMID- 22949580
TI  - Perceptions of plain and branded cigarette packaging among Norwegian youth and
      adults: a focus group study.
AB  - INTRODUCTION: In Norway, packaging is one of the few remaining ways for tobacco
      companies to promote their products. Plain packaging of tobacco products could be
      a means to limit this promotion. METHODS: Eleven focus group interviews with
      daily, occasional, and former smokers and nonsmokers (N = 69) aged 16-50 were
      undertaken to explore perceptions of different cigarette brands, the role of
      package design in communicating brand images, and how participants perceived
      cigarette packages when important design elements such as colors, symbols, logos,
      and branded fonts were removed. RESULTS: Distinct images of brands and user
      identities associated with these were narrated. Elements of the package design
      such as colors, images, and fonts were described as configuring brand images.
      Compared with current, completely branded cigarette packages, packages that
      displayed progressively fewer branding design elements were perceived
      increasingly unfavorably and as detracting from the images that packages
      otherwise communicate. CONCLUSIONS: The findings indicate that packaging is vital
      to consumer identification with and differentiation between cigarette brands and
      that a policy of plain packaging could be useful in reducing the impact of
      packaging in promotion of tobacco products.

PMID- 22949582
TI  - Effects of abstinence in adolescent tobacco smokers: withdrawal symptoms, urge,
      affect, and cue reactivity.
AB  - INTRODUCTION: The aim of this study was to evaluate abstinence effects in
      adolescent daily smokers by examining the effects of experimentally manipulated
      acute smoking abstinence on measures including: (a) withdrawal symptoms, (b)
      reactive irritability, (c) smoking urges, (d) affect, and (e) responses to
      smoking cues. METHODS: Participants (ages 13-19, 74 daily smokers, and 22
      nonsmokers) completed baseline questionnaires and laboratory assessments (Session
      1) and returned 1-4 days later to repeat the laboratory assessments (Session 2);
      half of the smokers were randomly assigned to overnight tobacco abstinence
      preceding Session 2. RESULTS: During Session 2, abstinent smokers reported
      significantly greater increases in withdrawal symptoms, smoking urges, and
      negative affect compared with smokers who did not abstain and compared with
      nonsmokers. Although there was not a significant effect of abstinence on
      differential reactivity to smoking versus neutral cues, abstinence did result in
      significantly increased peak provoked urges and negative effect. There was not a
      significant effect of abstinence on positive affect or reactive irritability,
      CONCLUSIONS: Our results suggest that adolescents experience increases in
      withdrawal symptoms, smoking urges (un-cued and peak provoked), and negative
      affect (un-cued and peak provoked) after acute smoking abstinence, but do not
      experience the increases in reactive irritability or decreases in positive affect
      that have been shown in adult smokers. Overall findings support the withdrawal
      relief and negative reinforcement models of smoking maintenance in adolescents
      and point to withdrawal, urge, and negative affect as important targets for
      treatment.

PMID- 22949581
TI  - Impact of tobacco regulation on animal research: new perspectives and
      opportunities.
AB  - INTRODUCTION: The Family Smoking Prevention and Tobacco Control Act in the United
      States and the World Health Organization Framework Convention on Tobacco or
      Health ratified by over 170 countries render scientific investigations into the
      abuse liability, harm, and effects of tobacco more critical than ever. A key area
      to explore relates to the potential regulation of nicotine content in cigarettes.
      Determining the nicotine content per cigarette below which smokers reliably
      reduce their consumption of and dependence on cigarettes, an idea proposed almost
      20 years ago (Benowitz & Henningfield, 1994), could be a powerful approach to
      reduce the abuse liability and consequent harm from cigarettes. However, this
      approach is laden with potentially complex issues. Many of these complications
      can be studied using animal models, but they require a particular perspective.
      METHODS: Herein, we review several challenges for animal researchers interested
      in nicotine reduction as examples of how this perspective dictates new approaches
      to animal research. These include defining the threshold nicotine dose for
      maintaining self-administration, evaluating the differential impact of various
      implementation strategies, assessing the factors that could interact with
      nicotine to alter the reinforcement threshold, describing the role of cues in
      maintaining low dose nicotine self-administration, and examining individual
      differences in response to nicotine reduction. CONCLUSIONS: Researchers who study
      tobacco using animal models have the opportunity to play a central role in the
      regulatory science of tobacco and conduct studies that directly inform policy
      decisions that could impact the lives of millions.

PMID- 22949583
TI  - Pharmacogenetic smoking cessation intervention in a health care setting: a pilot
      feasibility study.
AB  - INTRODUCTION: There is increasing evidence that response to pharmacological
      treatment for nicotine dependence may be moderated by genetic polymorphisms.
      However, the feasibility, acceptability, and impact of genetically tailoring
      treatment in real-world clinical settings are unknown. METHODS: We conducted a
      multiphased, mixed-methods feasibility study with current smokers to develop and
      evaluate a patient-centered, theoretically grounded personalized medicine
      treatment protocol. The initial research phase included formative work to develop
      intervention materials. The second phase included a randomized pilot trial to
      evaluate the intervention. Trial participants (n = 36) were genotyped for ANKK1
      rs1800497 and were randomized to receive genetic feedback (GF) plus standard
      behavioral counseling (BC) for smoking cessation or BC without GF. All
      participants received genetically tailored pharmacotherapy (nicotine patch or
      bupropion). RESULTS: The intervention was feasible to implement and was
      acceptable to participants based on satisfaction ratings and objective measures
      of participation. There was no evidence that the GF resulted in adverse
      psychological outcomes (e.g., depression, fatalism, reduced perceived control
      over quitting, differential motivation for quitting) based on quantitative or
      qualitative outcomes. CONCLUSIONS: Study results suggest that it is feasible to
      offer treatment within a health care setting that includes genetically tailored
      pharmacotherapy and doing so had no apparent adverse psychological impacts.
      Further evaluation of pharmacogenetically tailored smoking cessation
      interventions appears warranted.

PMID- 22949584
TI  - Native, discount, or premium brand cigarettes: what types of cigarettes are
      Canadian youth currently smoking?
AB  - INTRODUCTION: The objective of the study was to determine the brand distribution
      of premium, discount, and native cigarette brands and to identify the factors
      associated with smoking these brands among a nationally representative sample of
      Canadian youth smokers. METHODS: Data from 3,137 current smokers in Grades 9-12
      participating in the 2008-2009 Youth Smoking Survey (YSS) were used to examine
      the prevalence and factors associated with different cigarette brand preferences.
      RESULTS: The most prevalent brand of cigarette smoked was premium cigarettes
      (44.7%), followed by discount cigarettes (33.7%), and to be native cigarettes
      (7.3%). There was significant variability in brand preference by province with
      the majority of youth in Atlantic Canada and Quebec smoking a discount brand of
      cigarettes and higher prevalence rates of native cigarette use in Ontario and
      Quebec. Respondents were more likely to smoke discount cigarettes if they were
      female, daily smokers, or if they only had $1-20 a week in spending money.
      Respondents were more likely to smoke native cigarettes if they were Aboriginal,
      heavier smokers, or if they reported having no weekly spending money.
      CONCLUSIONS: A significant proportion of students from Grade 9 to 12 in Canada
      smoke cigarettes that are more affordable than premium brands and it appears that
      the market share for these more affordable cigarette options has increased in
      recent years. Given that the price of cigarettes is an important determinant in
      youth smoking behavior, it is critical to develop and continue to enforce tobacco
      control strategies designed to eliminate access to cheaper sources of cigarettes
      among youth populations.

PMID- 22949585
TI  - Acute respiratory symptoms following massive carbon black exposure.
AB  - BACKGROUND: Chronic carbon black exposure in the work environment can cause both
      respiratory symptoms and changes in lung function. There is limited information
      on the respiratory effects of acute exposure to carbon black. METHODS: Case
      report and literature review. RESULTS: A 44-year-old man had intense exposure to
      carbon black when his crane ran into a truck with a trailer filled with carbon
      black. One week after this exposure he developed shortness of breath and cough
      with sputum production. These symptoms persisted and increased in intensity.
      Physical examination revealed expiratory wheezes when in the supine position.
      Pulmonary function tests revealed a mild obstructive ventilatory defect with a
      reduced FEV(1)/FVC ratio. The patient responded to treatment with fluticasone and
      salmeterol with a reduction in symptoms and improvement in his spirometry to a
      normal range. CONCLUSIONS: Acute exposure to carbon black can cause respiratory
      symptoms and an obstructive ventilatory defect. This presentation suggests a
      small airway disease which improved over time with inhaled steroids and long
      acting beta-agonists. Patients with intense carbon black exposure following
      industrial accidents will need frequent evaluation to manage any related
      respiratory tract injury.

PMID- 22949586
TI  - Cancer incidence in UK electricity generation and transmission workers, 1973
      2008.
AB  - BACKGROUND: The effects of magnetic field exposure on cancer risks remains
      unclear. AIMS: To examine cancer incidence among a cohort of UK electricity
      generation and transmission workers. METHODS: Cancer morbidity experienced by a
      cohort of 81 842 employees of the former Central Electricity Generating Board of
      England and Wales was investigated for the period 1973-2008. All employees had
      worked for at least 6 months with some employment between 1973 and 1982.
      Standardized registration ratios (SRRs) were calculated on the basis of national
      rates. RESULTS: Overall cancer morbidity was slightly below expectation in males
      and females. Significant excesses were found in male workers for mesothelioma
      (Observed [Obs] 504, SRR 331), skin cancer (non-melanoma) (Obs 3187, SRR 107) and
      prostate cancer (Obs 2684, SRR 107) and in female workers for cancer of the small
      intestine (Obs 10, SRR 306) and nasal cancer (Obs 9, SRR 474). Brain cancers were
      close to expectation in males and below expectation in females. Leukaemia
      incidence (all types) was slightly below expectation in males and females. More
      detailed analyses showed import ant contrasts for mesothelioma and leukaemia.
      CONCLUSIONS: The clear occupational excess of mesothelioma was not matched by a
      corresponding excess of lung cancer, and the level of asbestos-induced lung
      cancer in this industry must be low. Leukaemia risks declined with period from
      hire; confident interpretation of this finding is not possible. The excesses of
      cancers of the nasal cavities and small intestine are probably not occupational,
      though the excess of skin cancer may be due to outdoor work.

PMID- 22949587
TI  - Analysis of minocycline as a countermeasure against acute radiation syndrome.
AB  - BACKGROUND/AIM: To evaluate the impact of an antibiotic, minocycline, on several
      immune parameters in response to radiation in a mouse model. MATERIALS AND
      METHODS: C57BL/6 mice were treated with minocycline (i.p.) for 5 days, beginning
      immediately before radiation with 1-3 Gy (60)Co gamma-rays. Spleen and blood were
      collected on day 4 post-irradiation. Cell populations were determined in the
      blood and spleen. Splenocytes were activated with anti-CD3 antibody for 48 h and
      cytokines were quantified. RESULTS: Minocycline increased the counts and/or
      percentages of splenic macrophages, granulocytes, natural killer, T- and CD8(+) T
      cells (p<0.05 versus radiation alone). Minocycline significantly increased the
      expression of interleukin-1alpha and beta, which are radioprotective, as well as
      the ones of granulocyte-macrophage colony-stimulating factor and granulocyte
      colony-stimulating factor, which accelerate neutrophil recovery (p<0.05 versus
      radiation alone), while suppressing cytokines that could prevent hematopoiesis,
      e.g. macrophage inflammatory protein-1alpha, tumor necrosis factor-alpha and
      interferon-gamma. CONCLUSION: These data indicate that minocycline should be
      further tested for use in restoration of the hematopoietic system after radiation
      exposure.

PMID- 22949588
TI  - Effects of curcumin and capsaicin irradiated with visible light on murine oral
      mucosa.
AB  - The purpose of this study was to evaluate the histopathological effects of
      curcumin and capsaicin, with or without visible light (VL) irradiation for 5 min,
      on the oral mucous membrane in mice. Capsaicin-treated, but not curcumin-treated,
      buccal epithelium exhibited slight tissue damage; VL irradiation caused excessive
      tissue damage, particularly when combined with the former treatment. The TdT
      mediated dUTP-biotin nick end-labeling (TUNEL) method demonstrated that both
      capsaicin and curcumin induced apoptosis, with the apoptotic effect of capsaicin
      appearing at an early stage of application. VL irradiation increased the number
      of apoptotic cells, particularly those upon in the capsaicin-treated area.
      Capsaicin and curcumin acted as photosensitizers exposure to VL, in the presence
      of oxygen. Curcumin and capsaicin with VL irradiation could thus be used for
      photodynamic therapy in the clinical setting, especially in precancerous oral
      diseases.

PMID- 22949589
TI  - A comparative study of phytoestrogen action in mitigating apoptosis induced by
      oxidative stress.
AB  - The phytoestrogens kaempferol, genistein and genistin were characterized using in
      vitro assays utilizing iodoacetic acid (IAA)-induced oxidative stress and
      mitochondrial dysfunction. RGC-5 cells were treated with different concentrations
      of IAA, and phytoestrogens were administered along with IAA. IAA is cytotoxic to
      RGC-5 cells and induces the generation of reactive oxygen species (ROS) in vitro.
      Genistein rescued RGC-5 cells in the presence of IAA, however, it also increased
      caspase activation and did not inhibit the generation of ROS. Genistein increased
      phosphorylation of ribosomal s6 kinase (p90RSK), reduced phosphorylation of the
      ribosomal S6 protein, and had no effect on phosphorylation of protein kinase B
      (AKT). Kaempferol and genistin rescued RGC-5 cells from IAA-induced cell death,
      as well as reduced caspase activation and ROS generation. Kaempferol increased
      phosphorylation of AKT and MAP kinase (p44/42). Genistin reduced phosphorylation
      of p42 and p90RSK. Although these phytoestrogens are flavonoids and similar in
      structure, they exhibit different effects on cell signaling.

PMID- 22949590
TI  - Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse
      pharmaceutical and biomedical properties.
AB  - Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var.
      chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO
      consist of nearly 70 constituents and have demonstrated numerous and diverse
      biomedical and pharmacological properties including (a) eradication of bacteria
      and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the
      mouth and saliva; (b) amelioration or dramatic reduction of symptoms of
      autoimmune diseases by inhibiting production of pro-inflammatory substances by
      activated macrophages, production of cytokines by peripheral blood mononuclear
      cells in patients with active Crohn's disease, and suppression of production of
      inflammatory cytokines and chemokines in an asthma model in mice; (c) protection
      of the cardiovascular system by effectively lowering the levels of total serum
      cholesterol, low-density lipoprotein and triglycerides in rats, and protection of
      low-density lipoprotein from oxidation in humans; (d) induction of apoptosis in
      human cancer cells in vitro and extensive inhibition of growth of human tumors
      xenografted in immunodeficient mice; and (e) improvement of symptoms in patients
      with functional dyspepsia. Collectively taken, these numerous and diverse medical
      and pharmaceutical properties of CMG and MGO warrant further research in an
      effort to enhance specific properties and identify specific constituent(s) that
      might be associated with each property.

PMID- 22949591
TI  - Spontaneous mutant ICR kuru2 might be another shaker-2 deaf mouse.
AB  - BACKGROUND: We have established a mouse model of spontaneous deafness by sib
      inbreeding over 10 years. The mouse was designated as kuru(2) and has been
      previously reported in this Journal. MATERIALS AND METHODS: In order to identify
      the genetic abnormality, the mouse was back-crossed to Mus musculus castaneus
      (CAST), and myosine 15 or myoXV on chromosome 11 was assumed to be the responsive
      gene. The background abnormality was identified by gene sequencing. RESULTS:
      Deletion of 2446 base pairs occurred in the mouse (from 28795 to 31241 in the
      complete sequence of the Mus musculus unconventional myosin-15 gene; NCBI
      accession: AF144093). DISCUSSION: The myosin ATP-binding site is present in the
      deleted area. Considering the function that the affected area regulates and
      previous reports, hearing loss of the examined mouse is attributable to the
      abnormality of the myoXV gene and this mouse might be another type of shaker-2
      deaf mouse.

PMID- 22949592
TI  - Effects of antibodies to EG-VEGF on angiogenesis in the chick embryo
      chorioallantoic membrane.
AB  - BACKGROUND: Endocrine gland-related vascular endothelial growth factor (EG-VEGF),
      is an angiogenic factor specifically targeting endothelial cells derived from
      endocrine tissues. The inhibition of the EG-VEGF/prokineticin receptor pathway
      could represent a selective antiangiogenic and anticancer strategy. AIM: to
      evaluate the impact of an antibody to EG-VEGF on the rapidly growing capillary
      plexus of the chick embryo chorioallantoic membrane (CAM). MATERIALS AND METHODS:
      The in ovo CAM assay was performed for the humanized EG-VEGF antibody. RESULTS:
      Hemorrhagic damage was induced in the capillaries, which led to early death of
      the embryos. Upon morphological staining, there was evidence of vascular
      disruption and extravasation of red blood cells in the chorion. Signs of
      vacuolization of the covering epithelium were also observed. CONCLUSION: Blocking
      endogenous EG-VEGF might represent a valuable approach of impairing or inhibiting
      angiogenesis in steroidogenic-derived embryonic tissues.

PMID- 22949593
TI  - Review: Impact of mediators present in amniotic fluid on preterm labour.
AB  - Preterm birth continues to be one of the most important issues in current
      obstetric medicine, being the single largest cause of perinatal morbidity and
      mortality. The signals that initiate preterm and term labour remain a mystery.
      Intrauterine inflammation with the secretion of cytokines is one of the accepted
      explanations for the mechanism of initiation of preterm labour. This review
      discusses the current understanding of the molecular mechanisms for the
      initiation of preterm labour, focusing chiefly on the role of intra-amniotic
      fluid mediators, whether endogenous or infection-induced, in the regulation of
      inflammatory response pathways associated with spontaneous preterm labour.
      Prostaglandins (PGs) are considered to be one of the key mediators of preterm
      labour, with the concentration of biologically active PGs in the amniotic fluid,
      particularly PGE(2) and PGF(2alpha), being significantly higher in women with
      preterm labour. Cytokines, such as interleukins and tumour necrosis factor alpha,
      additionally play a dominant role in preterm labour, particularly in association
      with infection. Elevated amniotic fluid concentrations of extracellular matrix
      mediators, including metalloproteases, are also implicated in the process of
      foetal membrane rupture in preterm labour. Allelic variations in the main
      amniotic fluid mediators may be the key to understanding the disparity in the
      rates of preterm birth between different ethnic populations. We also discuss the
      role of other potential mediators such as cell-adhesion molecules, nitric oxide
      and novel biomarkers found in the amniotic fluid.

PMID- 22949594
TI  - Influence of maternal smoking during pregnancy on oxidant status in amniotic
      fluid.
AB  - BACKGROUND: Approximately 20% of women in Germany are smokers, and some of them
      are unable to stop smoking during pregnancy. As cigarette smoke generates free
      radicals, it has been suggested that it may be one of the major sources of
      oxidant stress in pregnant women and unborn fetuses. On the other hand, the human
      placenta is known to be a major source of pro-oxidant agents, antioxidant enzyme
      systems, and hormones, and is able to keep lipid peroxidation under control in
      normal pregnancy. The aim of the present study was to determine whether it is
      possible to detect antioxidants in amniotic fluid using the Esterbauer method and
      to analyze whether there are any differences in the oxidant status of the
      amniotic fluid between smoking and non-smoking mothers. The results were
      confirmed by two assays measuring the total antioxidant capacity (TAC), as well
      as the malon dialdehyde concentration (MDA) in the amniotic fluid of smoking and
      non-smoking mothers. MATERIALS AND METHODS: Differences in low-density
      lipoprotein (LDL) susceptibility to oxidation were measured using the Esterbauer
      method in the amniotic fluid of smoking and non-smoking mothers. RESULTS: The
      results showed that there was a significant difference in the duration of
      susceptibility of LDL to oxidation between smokers and non-smokers (49.47 +/-
      24.78 min, n=20 and 31.94 +/- 14.26 min, n=67; p=0.006). Arithmetic average of
      MDA was higher in smokers than in non-smokers (11 pmol/mg and 6 pmol/mg); for TAC
      it was vice versa 840 mM vs. 1054 mM. CONCLUSION: Measuring the lag phase of LDL
      oxidation makes it possible to study antioxidative effects. As the lag phase was
      significantly longer in smokers than in non-smokers, it can be assumed that there
      must be a substance in the amniotic fluid of smokers which has antioxidative
      power, inhibits LDL oxidation, and intercepts radicals. It can be assumed that
      the fetoplacental unit has mechanisms to react against tobacco smoke inhaled by
      the mother.

PMID- 22949595
TI  - New findings concerning the mutual action of hormones and receptors.
AB  - The actual mechanisms concerning the role of the hormone-receptor complex cannot
      satisfactorily explain the various hormone activities. Photobiological studies
      were performed in order to gain a deeper insight in this respect. 17beta
      estradiol (17betaE(2)) was used as representative hormone and methionine
      enkephaline (ME) was used as an adequate model for a receptor. Their biological
      behaviors and mutual interactions were investigated in air-free media (pH~7.4; 37
      degrees C) by excitation in singlet state, using monochromatic UV-light
      (lambda=254 nm; E=4.85 eV/heta). It was found that tyrosine (Tyr) as a main
      component of ME, as well as ME itself, can eject solvated electrons (e(aq)(-)),
      when excited in singlet state. The observed quantum yields, Q (e(aq)(-)), in both
      cases decreased with an increase of the corresponding substrate concentration.
      The effect is explained by the formation of associates (unstable complexes of
      molecules prevailing in the ground state), which consume a proportion of the
      emitted e(aq)(-). The ME transients, resulting from the electron emission, can
      partly regenerate by electron transfer from an efficient electron donor, e.g.
      ascorbate. 17betaE(2), like other hormones, can also eject electrons under the
      same experimental conditions. In a mix of 17betaE(2) and ME in air-free media
      (40/60 water/ethanol, pH~7.4; 37 degrees C), a mutual electron exchange takes
      place. Thereby 17betaE(2) transients, being in status nascendy state, can partly
      regenerate by electron transfer from ME. Thus, the duration and action of
      17betaE(2) are prolonged. To our knowledge this fact is reported for the first
      time and it is a finding of basic biological and medical importance.

PMID- 22949596
TI  - Comparison of nine media in the culture of human ovarian granulosa lutein cells.
AB  - BACKGROUND: Cultures of human ovarian granulosa lutein (hGL) cells are broadly
      used in experimental studies. The choice of the culture medium is important for
      the optimization of the conditions for culture of hGL cells. AIM: To compare the
      efficiency of a basic salt solution and eight different defined media on the
      culture of hGL cells. MATERIALS AND METHODS: Cultures of the HGL-5 cell line were
      maintained for 72 hours with DMEM/F12, RPMI-1640, Ham'sF10, Modified Ham'sF10(r),
      HTFXtra(r), Global(r), Complete Multiblast(r), Universal(r) or Earle's balanced
      salt solution (EBSS). At the end of the culturing period, the attachment, the
      viability and the total number of cells were measured. RESULTS: Culture in
      DMEM/F12 led to the highest score of all studied parameters, followed by RPMI
      1640. The lowest performance was recorded with Complete Multiblast(r) and EBSS.
      The use of the other media gave mediocre results. CONCLUSION: Among the media
      tested, DMEM/F12 appears to be the best choice for the culture of hGL cells.

PMID- 22949597
TI  - Doxorubicin induces early embryo apoptosis by inhibiting poly(ADP ribose)
      polymerase.
AB  - BACKGROUND: The effect of Doxorubicin, a widely used chemotherapeutic agent, on
      early mouse embryonic development has not been previously characterized.
      MATERIALS AND METHODS: Expression of apoptosis-related genes and poly(ADP-ribose)
      polymerase (PARP) family genes were assessed by real-time reverse transcription
      polymerase chain reaction (RT-PCR). Apoptosis in mouse blastocysts was tested
      using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      assay. Cleaved (c)-PARP was analyzed by western blot. RESULTS: A 20 h exposure to
      doxorubicin caused rapid cytoplasmic fragmentation, DNA condensation and
      disruption of the cytoskeleton in mouse embryos. Doxorubicin altered the
      expression of genes involved in DNA repair and apoptosis and blocked early
      embryonic development, suggesting that doxorubicin affects DNA synthesis and
      repair. Furthermore, the effect of doxorubicin on early embryo development was
      determined by assessing the rates of development to different stages and an
      apoptosis index. Both assays confirmed that doxorubicin altered embryonic
      development. In conclusion, doxorubicin blocked pre-implantation development in
      early mouse embryos by altering apoptosis-related gene expression and
      inactivating DNA repair by PARP.

PMID- 22949598
TI  - The effects of cetrorelix and triptorelin on the viability and steroidogenesis of
      cultured human granulosa luteinized cells.
AB  - BACKGROUND: We investigated the effects of the gonadotropin-releasing hormone
      (GnRH) agonist triptorelin as well the GnRH antagonist cetrorelix those of on the
      viability and steroidogenesis in human granulosa luteinized (hGL) cell cultures.
      MATERIALS AND METHODS: The hGL cells were obtained from 34 women undergoing
      ovarian stimulation for IVF treatment. The cells were cultured for 48 h with or
      without 1 nM or 3 nM of cetrorelix or triptorelin in serum-free media. The cell
      viability was evaluated by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl
      tetrazolium bromide] assay. The concentrations of estradiol and progesterone in
      culture supernatants were measured by ELISA. RESULTS: Treatment with triptorelin
      slightly increased cell viability, whereas treatment with 3 nM cetrorelix led to
      a significant decrease. Estradiol concentrations were reduced with 3 nM
      triptorelin. Cultures treated with high-dose of either cetrorelix or triptorelin
      tended to secrete less progesterone than controls. CONCLUSION: Cetrorelix
      significantly reduces the viability of hGL cells. Triptorelin and cetrorelix may
      have minor effects on steroidogenesis. These results suggest that GnRH analogues
      may influence ovarian functions.

PMID- 22949599
TI  - Treatment of sleep apnoea using a mandibular advancement splint--an open
      prospective study.
AB  - Obstructive sleep apnoea (OSA) may cause considerable disturbances, including the
      development of health problems. This study was performed in order to evaluate the
      results of treating OAS with a mandibular advancement splint (MAS), and to
      evaluate the effects of this treatment. This was a prospective open longitudinal
      study. Ninety patients were randomly selected and included in the study. All 90
      patients received an MAS. Forty-eight patients concluded the study, whereas 27
      dropped-out and 15 were excluded. The sleep pattern was monitored at home with
      portable equipment. There was a clear tendency towards a reduction in the
      apnoea/hypopnea index (AHI) and the oxygen desaturation index (ODI) between the
      two investigations. Furthermore, there was a tendency towards reduced sleep
      apnoea; ratings on the Epworth sleepiness scale were lower, indicating a
      reduction in daytime sleepiness. Treatment with MAS in our study reduced sleep
      apnoea and snoring, and lowered the values of the Epworth sleepiness scale,
      indicating a reduction in daytime sleepiness in the majority of the patients.
      Lifestyle factors are not believed to have affected the results.

PMID- 22949600
TI  - An odontogenic keratocystic tumor in the buccal space: an unusual site of origin
      and a review of the literature.
AB  - AIM: Keratocystic odontogenic tumors (KCOTs) arise from remnants of epithelial
      structures associated with the development of teeth and occur predominantly
      intraosseously. In rare occasions they can appear extraosseously in the gingiva
      as peripheral counterparts; only 15 cases have been reported to date. Evenmore
      rare are cases of KCOTs of the buccal soft tissues. The aim of this report is to
      present a rare case of KCOT affecting the buccal soft tissue as an original site
      and a review of the literature regarding diagnostic and therapeutic options.

PMID- 22949601
TI  - Obesity effects on cyclophosphamide-induced DNA damage in hematopoietic cell
      transplant recipients.
AB  - BACKGROUND: Cyclophosphamide, an alkylating agent, is metabolically activated to
      phosphoramide mustard, to form toxic DNA-DNA (G-NOR-G) crosslinks. Increased
      exposure to cyclophosphamide metabolites has been associated with treatment
      related toxicity. The effect of obesity on exposure to cyclophosphamide-induced G
      NOR-G crosslinks is not known. Therefore we sought to determine whether obesity
      affects the formation of cyclophosphamide-specific G-NOR-G crosslinks. PATIENTS
      AND METHODS: Plasma cyclophosphamide concentrations and blood cell G-NOR-G
      amounts were measured. RESULTS: Overweight/obese patients received a
      significantly higher daily cyclophosphamide dose (median 3000 vs. 4450 mg,
      p<0.01). Despite the higher doses, overweight/obese patients had lower exposure
      to cyclophosphamide compared to lean patients with an area under the curve (AUC(0
      infinity)) =529.24 vs. 867.99 MUcg/ml*h respectively, p<0.01. G-NOR-G amounts
      were similar in overweight/obese and lean subjects, AUC(0-infinity)=142.8 vs.
      147.0 adducts/10(6) nucleotides*h, respectively, p=0.59. CONCLUSION:
      Overweight/obese patients have altered metabolism and disposition of
      cyclophosphamide. This altered exposure may be an important determinant of
      efficacy and may play a role in treatment-related mortality.

PMID- 22949602
TI  - An easy method to quantify plasma cells in caeliac disease.
AB  - BACKGROUND: Caeliac disease is a common immune-mediated condition in the proximal
      small intestine, generated by a permanent intolerance to cereal gluten proteins
      in genetically predisposed individuals. It has become apparent that abnormal
      microbiota proliferate in the duodenal lumen of patients with caeliac disease.
      Recently it was also noticed that an antibody against multiple myeloma oncogene
      1/IRF4 (MUM1) stained plasma cells and their precursors. MATERIALS AND METHODS:
      Eleven consecutive duodenal biopsies were investigated; four had villous atrophy
      (caeliac patients) and the remaining seven exhibited histologically normal mucosa
      (non-caeliac patients). Sections were stained with H&E and with anti-MUM1. A
      graticulated eyepiece (10 mm, divided into 10 * 10 squares) was used for counting
      of MUM1-expressing cells in the superficial compartment (SC) and in the deep
      compartment (DC) of the lamina propria mucosa (lpm). RESULTS: In the duodenal
      mucosa of caeliac patients the mean number of MUM1-labelled cells in 12 areas of
      the lpm was 67.1 (range 37-88) in the SC and 61.5 (range 42-84) in the DC. In the
      duodenal mucosa of non-caeliac patients, the mean number of MUM1-labelled cells
      in 21 areas of the lpm was 7.6 (range 0-24) in the SC, and 29.2 (range 22-40) in
      the DC (p<0.05). CONCLUSION: These preliminary results showed that a
      significantly higher number of plasma cells/plasma cell precursors accumulate in
      the lpm in patients with caeliac disease, particularly in the SC. This abnormal
      accumulation of MUM1-expressing cells might be a defence mechanism against the
      alien bacterial flora recently reported in the duodenal microenvironment in
      caeliac patients. This appears to be the first report in which MUM1
      immunostaining is applied to assess the frequency of plasma cell precursors in
      the duodenal mucosa in caeliac patients.

PMID- 22949603
TI  - Comparing bioelectrical impedance values in assessing early upper limb lymphedema
      after breast cancer surgery.
AB  - AIM: The purpose of this prospective study was to evaluate resistance (R) and
      phase angle (Pa) determined by single-frequency whole-body bioelectrical
      impedance analysis (BIA), as predictors for the early onset of edema of the upper
      limb in patients undergoing surgical treatment for breast cancer. MATERIALS AND
      METHODS: Whole-body BIA was performed before surgery, as well as at two days, at
      one and three months after surgery. RESULTS: A total of 33 women undergoing
      breast cancer surgery were examined. Four patients developed an edema of the
      upper limb within the first three months after surgery. Both analyzed parameters
      showed a fairly good performance in terms of sensitivity (R=75%, Pa=75%) and
      specificity (R=86%, Pa=83%). The positive predictive values of 43% (R) and 38%
      (Pa) were unsatisfactory, whereas the negative predictive values were 96% for
      both parameters. CONCLUSION: Pa, as well as R, in whole-body BIA can be used to
      rule out a developing edema of the upper limb.

PMID- 22949604
TI  - The impact of ultrasound contrast medium administration on the right ventricle in
      patients with heart failure.
AB  - BACKGROUND: The purpose of the present study was to examine the effect of
      SonoVueTM on right ventricular (RV) dimensions and contractility in patients with
      heart failure. PATIENTS AND METHODS: Twenty-four patients were divided into two
      groups. Group A consisted of 15 patients with heart failure and group B (control)
      of nine patients without heart disease. SonoVue was administered at low (2 ml)
      and high (4 ml) doses in both groups separately, in a random order. RV
      dimensions, contractility, peak systolic pressure gradient from tricuspid
      regurgitation (TRPG) and the time to maximal RV end-diastolic dimension (EDD), as
      well as the time for RV-EDD to return to the baseline value (recovery), were
      calculated in every cardiac cycle starting before the administration of SonoVue
      (baseline) until the recovery of RV-EDD. RESULTS: Low-(group A, p<0.001 and group
      B, p<0.05) and high-dose (group A, p<0.0001 and group B, p<0.01) contrast
      infusion increased the RV-EDD compared to baseline values. TRPG increased
      significantly (p<0.05) in both groups, under low-as well as high-dose. In group
      A, high-dose compared to low-dose produced a significant delay in the time
      duration to max RV-EDD (p<0.05) and in the time to RV-EDD recovery (p<0.0001).
      CONCLUSION: The administration of SonoVue in patients with heart failure was
      followed by an acute, transient, dose-dependent increase in RV-EDD and TRPG,
      without any effect on RV contractility.

PMID- 22949605
TI  - Positive parenting, not physical punishment.

PMID- 22949606
TI  - Consent requirements for pelvic examinations.

PMID- 22949607
TI  - Consent requirements for pelvic examinations.

PMID- 22949609
TI  - Growing up with a cochlear implant: education, vocation, and affiliation.
AB  - The long-term educational/vocational, affiliation, and quality-of-life outcomes
      of the first and second cohorts of children with bilateral, profound hearing loss
      who received cochlear implants under a large National Institutes of Health-funded
      study was investigated in 41 of 61 eligible participants. Educational and
      vocational outcomes were collected from user survey data. Affiliation and quality
      of-life data were collected from the Satisfaction-with-Life scale and the Deaf
      Identity Scale. Qualitative results indicated that compared with their hearing,
      adult-age peers, this group obtained high educational achievement, and they
      reported a very high satisfaction of life. With respect to forming an identity in
      these first 2 cohorts of cochlear implant users, we found that most of the
      individuals endorsed a dual identity, which indicates they feel just as
      comfortable with Deaf individuals as they do with hearing individuals.
      Quantitative results revealed a significant relationship between ability to hear
      and ability to speak, in addition to consistency of device use. Additional
      relationships were found between mother's and the individual's educational
      statuses, hearing scores, and communication system used. Younger individuals
      scored higher on satisfaction-with-life measures, and they also tended to endorse
      a dual identity more often. Taken together, these findings diminish concerns that
      profoundly deaf individuals growing up with cochlear implants will become
      culturally bereft and unable to function in the hearing world.

PMID- 22949610
TI  - An interview with Haruhiko Koseki. Interviewed by Eva Amsen.

PMID- 22949611
TI  - Epithelial-mesenchymal transitions: insights from development.
AB  - Epithelial-mesenchymal transition (EMT) is a crucial, evolutionarily conserved
      process that occurs during development and is essential for shaping embryos. Also
      implicated in cancer, this morphological transition is executed through multiple
      mechanisms in different contexts, and studies suggest that the molecular programs
      governing EMT, albeit still enigmatic, are embedded within developmental programs
      that regulate specification and differentiation. As we review here, knowledge
      garnered from studies of EMT during gastrulation, neural crest delamination and
      heart formation have furthered our understanding of tumor progression and
      metastasis.

PMID- 22949612
TI  - Tooth shape formation and tooth renewal: evolving with the same signals.
AB  - Teeth are found in almost all vertebrates, and they therefore provide a general
      paradigm for the study of epithelial organ development and evolution. Here, we
      review the developmental mechanisms underlying changes in tooth complexity and
      tooth renewal during evolution, focusing on recent studies of fish, reptiles and
      mammals. Mammals differ from other living vertebrates in that they have the most
      complex teeth with restricted capacity for tooth renewal. As we discuss, however,
      limited tooth replacement in mammals has been compensated for in some taxa by the
      evolution of continuously growing teeth, the development of which appears to
      reuse the regulatory pathways of tooth replacement.

PMID- 22949613
TI  - Tup/Islet1 integrates time and position to specify muscle identity in Drosophila.
AB  - The LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component
      of cardiogenesis in Drosophila and vertebrates. We report here an additional
      major role for Drosophila Tup in specifying dorsal muscles. Tup is expressed in
      the four dorsal muscle progenitors (PCs) and tup-null embryos display a severely
      disorganized dorsal musculature, including a transformation of the dorsal DA2
      into dorsolateral DA3 muscle. This transformation is reciprocal to the DA3 to DA2
      transformation observed in collier (col) mutants. The DA2 PC, which gives rise to
      the DA2 muscle and to an adult muscle precursor, is selected from a cluster of
      myoblasts transiently expressing both Tinman (Tin) and Col. The activation of tup
      by Tin in the DA2 PC is required to repress col transcription and establish DA2
      identity. The transient, partial overlap between Tin and Col expression provides
      a window of opportunity to distinguish between DA2 and DA3 muscle identities. The
      function of Tup in the DA2 PC illustrates how single cell precision can be
      reached in cell specification when temporal dynamics are combined with positional
      information. The contributions of Tin, Tup and Col to patterning Drosophila
      dorsal muscles bring novel parallels with chordate pharyngeal muscle development.

PMID- 22949614
TI  - SPACA1-deficient male mice are infertile with abnormally shaped sperm heads
      reminiscent of globozoospermia.
AB  - SPACA1 is a membrane protein that localizes in the equatorial segment of
      spermatozoa in mammals and is reported to function in sperm-egg fusion. We
      produced a Spaca1 gene-disrupted mouse line and found that the male mice were
      infertile. The cause of this sterility was abnormal shaping of the sperm head
      reminiscent of globozoospermia in humans. Disruption of Spaca1 led to the
      disappearance of the nuclear plate, a dense lining of the nuclear envelope facing
      the inner acrosomal membrane. This coincided with the failure of acrosomal
      expansion during spermiogenesis and resulted in the degeneration and
      disappearance of the acrosome in mature spermatozoa. Thus, these findings clarify
      part of the cascade leading to globozoospermia.

PMID- 22949615
TI  - The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase
      Smurf1 in the control of axon growth.
AB  - Axon growth is an essential event during brain development and is extremely
      limited due to extrinsic and intrinsic inhibition in the adult brain. The E3
      ubiquitin ligase Cdh1-anaphase promoting complex (APC) has emerged as an
      important intrinsic suppressor of axon growth. In this study, we identify in
      rodents the E3 ligase Smurf1 as a novel substrate of Cdh1-APC and that Cdh1
      targets Smurf1 for degradation in a destruction box-dependent manner. We find
      that Smurf1 acts downstream of Cdh1-APC in axon growth and that the turnover of
      RhoA by Smurf1 is important in this process. In addition, we demonstrate that
      acute knockdown of Smurf1 in vivo in the developing cerebellar cortex results in
      impaired axonal growth and migration. Finally, we show that a stabilized form of
      Smurf1 overrides the inhibition of axon growth by myelin. Taken together, we
      uncovered a Cdh1-APC/Smurf1/RhoA pathway that mediates axonal growth suppression
      in the developing mammalian brain.

PMID- 22949616
TI  - ISWI contributes to ArsI insulator function in development of the sea urchin.
AB  - Insulators are genomic elements that regulate transcriptional activity by forming
      chromatin boundaries. Various DNA insulators have been identified or are
      postulated in many organisms, and the paradigmatic CTCF-dependent insulators are
      perhaps the best understood and most widespread in function. The diversity of DNA
      insulators is, however, understudied, especially in the context of embryonic
      development, when many new gene territories undergo transitions in functionality.
      Here we report the functional analysis of the arylsulfatase insulator (ArsI)
      derived from the sea urchin, which has conserved insulator activity throughout
      the many metazoans tested, but for which the molecular mechanism of function is
      unknown. Using a rapid in vivo assay system and a high-throughput mega-shift
      assay, we identified a minimal region in ArsI that is responsible for its
      insulator function. We discovered a small set of proteins specifically bound to
      the minimal ArsI region, including ISWI, a known chromatin-remodeling protein.
      During embryogenesis, ISWI was found to interact with select ArsI sites
      throughout the genome, and when inactivated led to misregulation of select gene
      expression, loss of insulator activity and aberrant morphogenesis. These studies
      reveal a mechanistic basis for ArsI function in the gene regulatory network of
      early development.

PMID- 22949618
TI  - Dynamic microtubules at the vegetal cortex predict the embryonic axis in
      zebrafish.
AB  - In zebrafish, as in many animals, maternal dorsal determinants are vegetally
      localized in the egg and are transported after fertilization in a microtubule
      dependent manner. However, the organization of early microtubules, their dynamics
      and their contribution to axis formation are not fully understood. Using live
      imaging, we identified two populations of microtubules, perpendicular bundles and
      parallel arrays, which are directionally oriented and detected exclusively at the
      vegetal cortex before the first cell division. Perpendicular bundles emanate from
      the vegetal cortex, extend towards the blastoderm, and orient along the animal
      vegetal axis. Parallel arrays become asymmetric on the vegetal cortex, and orient
      towards dorsal. We show that the orientation of microtubules at 20 minutes post
      fertilization can predict where the embryonic dorsal structures in zebrafish will
      form. Furthermore, we find that parallel microtubule arrays colocalize with wnt8a
      RNA, the candidate maternal dorsal factor. Vegetal cytoplasmic granules are
      displaced with parallel arrays by ~20 degrees , providing in vivo evidence of a
      cortical rotation-like process in zebrafish. Cortical displacement requires
      parallel microtubule arrays, and probably contributes to asymmetric transport of
      maternal determinants. Formation of parallel arrays depends on Ca(2+) signaling.
      Thus, microtubule polarity and organization predicts the zebrafish embryonic
      axis. In addition, our results suggest that cortical rotation-like processes
      might be more common in early development than previously thought.

PMID- 22949617
TI  - Promoter DNA methylation couples genome-defence mechanisms to epigenetic
      reprogramming in the mouse germline.
AB  - Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of
      the comprehensive epigenetic reprogramming that occurs during PGC development.
      5mC plays an important role in maintaining stable gene silencing and repression
      of transposable elements (TE) but it is not clear how the extensive loss of DNA
      methylation impacts on gene expression and TE repression in developing PGCs.
      Using a novel epigenetic disruption and recovery screen and genetic analyses, we
      identified a core set of germline-specific genes that are dependent exclusively
      on promoter DNA methylation for initiation and maintenance of developmental
      silencing. These gene promoters appear to possess a specialised chromatin
      environment that does not acquire any of the repressive H3K27me3, H3K9me2,
      H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation.
      Intriguingly, this methylation-dependent subset is highly enriched in genes with
      roles in suppressing TE activity in germ cells. We show that the mechanism for
      developmental regulation of the germline genome-defence genes involves DNMT3B
      dependent de novo DNA methylation. These genes are then activated by lineage
      specific promoter demethylation during distinct global epigenetic reprogramming
      events in migratory (~E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that
      genes involved in genome defence are developmentally regulated primarily by
      promoter DNA methylation as a sensory mechanism that is coupled to the potential
      for TE activation during global 5mC erasure, thereby acting as a failsafe to
      ensure TE suppression and maintain genomic integrity in the germline.

PMID- 22949619
TI  - An inwardly rectifying K+ channel is required for patterning.
AB  - Mutations that disrupt function of the human inwardly rectifying potassium
      channel KIR2.1 are associated with the craniofacial and digital defects of
      Andersen-Tawil Syndrome, but the contribution of Kir channels to development is
      undefined. Deletion of mouse Kir2.1 also causes cleft palate and digital defects.
      These defects are strikingly similar to phenotypes that result from disrupted
      TGFbeta/BMP signaling. We use Drosophila melanogaster to show that a Kir2.1
      homolog, Irk2, affects development by disrupting BMP signaling. Phenotypes of
      irk2 deficient lines, a mutant irk2 allele, irk2 siRNA and expression of a
      dominant-negative Irk2 subunit (Irk2DN) all demonstrate that Irk2 function is
      necessary for development of the adult wing. Compromised Irk2 function causes
      wing-patterning defects similar to those found when signaling through a
      Drosophila BMP homolog, Decapentaplegic (Dpp), is disrupted. To determine whether
      Irk2 plays a role in the Dpp pathway, we generated flies in which both Irk2 and
      Dpp functions are reduced. Irk2DN phenotypes are enhanced by decreased Dpp
      signaling. In wild-type flies, Dpp signaling can be detected in stripes along the
      anterior/posterior boundary of the larval imaginal wing disc. Reducing function
      of Irk2 with siRNA, an irk2 deletion, or expression of Irk2DN reduces the Dpp
      signal in the wing disc. As Irk channels contribute to Dpp signaling in flies, a
      similar role for Kir2.1 in BMP signaling may explain the morphological defects of
      Andersen-Tawil Syndrome and the Kir2.1 knockout mouse.

PMID- 22949621
TI  - Interspecies mobilization of an ermT-carrying plasmid of Streptococcus
      dysgalactiae subsp. equisimilis by a coresident ICE of the ICESa2603 family.
AB  - OBJECTIVES: The recently documented presence of almost identical, small, non-self
      transmissible, erm(T)-carrying plasmids in clonally unrelated erythromycin
      resistant isolates of Streptococcus pyogenes and Streptococcus agalactiae
      suggests that these plasmids somehow circulate in the streptococcal population.
      The objective of this study was to characterize the erm(T)-carrying genetic
      element in a clinical isolate of Streptococcus dysgalactiae subsp. equisimilis
      (Sde5580) and to provide a possible explanation for the spread of erm(T)-carrying
      plasmids in streptococci. METHODS: The erm(T)-carrying element of Sde5580 was
      investigated by plasmid analysis, PCR experiments and sequencing. Transfer and
      retransfer experiments were performed using S. pyogenes, S. agalactiae and
      Streptococcus suis strains as recipients and by selection in the presence of
      suitable drug concentrations. Transconjugants were analysed by SmaI
      macrorestriction analysis. Genetic studies also included PCR-restriction fragment
      length polymorphism analysis using HindIII endonuclease. RESULTS: Sde5580
      contained two mobile genetic elements: a 4950 bp erm(T)-carrying plasmid (p5580)
      almost identical to the non-self-transmissible erm(T)-carrying plasmids of S.
      pyogenes and S. agalactiae mentioned above, and an ~63 kb cadC/cadA-carrying
      integrative and conjugative element (ICESde3396-like) of the ICESa2603 family.
      p5580 was transferable at high frequency to the recipients of all three species
      through in trans mobilization by the coresident ICESde3396-like element. p5580
      and ICESde3396-like were able to be transferred either separately or together.
      CONCLUSIONS: This is the first evidence of horizontal transfer of an erm(T)
      carrying plasmid between streptococci. In trans mobilization by coresident ICEs
      may be one mechanism for the spread of erm(T)-carrying plasmids in the
      streptococcal population.

PMID- 22949620
TI  - Dissecting the molecular bridges that mediate the function of Frizzled in planar
      cell polarity.
AB  - Many epithelia have a common planar cell polarity (PCP), as exemplified by the
      consistent orientation of hairs on mammalian skin and insect cuticle. One
      conserved system of PCP depends on Starry night (Stan, also called Flamingo), an
      atypical cadherin that forms homodimeric bridges between adjacent cells. Stan
      acts together with other transmembrane proteins, most notably Frizzled (Fz) and
      Van Gogh (Vang, also called Strabismus). Here, using an in vivo assay for
      function, we show that the quintessential core of the Stan system is an
      asymmetric intercellular bridge between Stan in one cell and Stan acting together
      with Fz in its neighbour: such bridges are necessary and sufficient to polarise
      hairs in both cells, even in the absence of Vang. By contrast, Vang cannot
      polarise cells in the absence of Fz; instead, it appears to help Stan in each
      cell form effective bridges with Stan plus Fz in its neighbours. Finally, we show
      that cells containing Stan but lacking both Fz and Vang can be polarised to make
      hairs that point away from abutting cells that express Fz. We deduce that each
      cell has a mechanism to estimate and compare the numbers of asymmetric bridges,
      made between Stan and Stan plus Fz, that link it with its neighbouring cells. We
      propose that cells normally use this mechanism to read the local slope of tissue
      wide gradients of Fz activity, so that all cells come to point in the same
      direction.

PMID- 22949622
TI  - Primary care clinicians' perceptions of antibiotic resistance: a multi-country
      qualitative interview study.
AB  - OBJECTIVES: To explore and compare primary care clinicians' perceptions of
      antibiotic resistance in relation to the management of community-acquired lower
      respiratory tract infection (LRTI) in contrasting European settings. METHODS:
      Qualitative interview study with 80 primary care clinicians in nine European
      countries. Data were subjected to a five-stage analytical framework approach
      (familiarization; developing a thematic framework from the interview questions
      and the themes emerging from the data; indexing; charting; and mapping to search
      for interpretations in the data). Preliminary analysis reports were sent to all
      network facilitators for validation. RESULTS: Most clinicians stated that
      antibiotic resistance was not a problem in their practice. Some recommended
      enhanced feedback about local resistance rates. Northern European respondents
      generally favoured using the narrowest-spectrum agent, motivated by containing
      resistance, whereas southern/eastern European respondents were more motivated by
      maximizing the potential of a rapid treatment effect and so justified empirical
      use of broad-spectrum antibiotics. Antibiotic treatment failure was ascribed
      largely to viral aetiology rather than resistant bacteria. Clinicians generally
      agreed that resistance will become more serious without enhanced antibiotic
      stewardship or new drug discovery. CONCLUSIONS: If current rates of antibiotic
      resistance are likely to result in important treatment failures, then provision
      of local resistance data is likely to enhance clinicians' sense of importance of
      the issue. Interventions to enhance the quality of antibiotic prescribing in
      primary care should address perceptions, particularly in the south and east of
      Europe, that possible advantages to patients from antibiotic treatment in
      general, and from newer broad-spectrum compared with narrow-spectrum agents,
      outweigh disadvantages to patients and society from associated effects on
      antibiotic resistance.

PMID- 22949623
TI  - Extended-spectrum-beta-lactamase- and AmpC-beta-lactamase-producing Escherichia
      coli in Dutch broilers and broiler farmers.
AB  - OBJECTIVES: The aim of this study was to establish the prevalence of extended
      spectrum beta-lactamase (ESBL)- and AmpC beta-lactamase-producing Escherichia
      coli at Dutch broiler farms and in farmers and to compare ESBL/AmpC-producing
      isolates from farmers and their animals. METHODS: Twenty-five to 41 cloacal swabs
      collected from broilers at each of 26 farms and 18 faecal samples from 18 broiler
      farmers were analysed for determination of the presence of ESBL/AmpC-producing E.
      coli. ESBL/AmpC genes were characterized by microarray, PCR and sequencing.
      Plasmids were characterized by transformation and PCR-based replicon typing.
      Subtyping of plasmids was done by plasmid multilocus sequence typing or
      restriction fragment length polymorphism. E. coli genotypes were determined by
      multilocus sequence typing. RESULTS: Birds from all farms were positive for
      ESBL/AmpC-producing E. coli, and on 22/26 farms the within-farm prevalence was >=
      80%. Six of 18 farmers carried isolates containing ESBL/AmpC genes bla(CTX-M-1),
      bla(CMY-2) and/or bla(SHV-12), which were also present in the samples from their
      animals. In five of these isolates, the genes were located on identical plasmid
      families [IncI1 (n = 3), IncK (n = 1) or IncN (n = 1)], and in isolates from two
      farmers the genes were carried on identical plasmid subtypes (IncI1 ST12 and IncN
      ST1, where ST stands for sequence type) as in the isolates from their animals.
      CONCLUSIONS: This study shows a high prevalence of birds carrying ESBL/AmpC
      producing E. coli at Dutch broiler farms and a high prevalence of ESBL/AmpC
      producing E. coli in farmers. This is undesirable due to the risk this poses to
      human health. Future research should focus on identification of the source of
      these isolates in the broiler production chain to make interventions resulting in
      reduction of these isolates possible.

PMID- 22949624
TI  - Five years of non-prescription oseltamivir: effects on resistance, immunization
      and stockpiling.
AB  - OBJECTIVES: In 2007 New Zealand (NZ) became the first country to make oseltamivir
      (Tamiflu(r)) available off-prescription. This study investigated the extent of
      pharmacist supply of oseltamivir over 5 years, including during the influenza
      A(H1N1) pandemic, and the impact of pharmacist supply of oseltamivir on influenza
      virus oseltamivir susceptibility, personal stockpiling and influenza vaccine
      uptake. METHODS: Randomly selected community pharmacies in NZ reported
      oseltamivir provision by prescription and through pharmacist supply from 1
      January 2007 to 15 September 2011. Oseltamivir resistance data on influenza
      viruses isolated during influenza surveillance from 2008 to 2011 were obtained,
      along with influenza vaccine uptake data from 2005 to 2011 and influenza
      detection data. RESULTS: Seventy of 85 eligible pharmacies completed the study
      (82% response rate). Most supplies of oseltamivir throughout the 5 years were
      dispensed against a prescription rather than pharmacist supplied, with pharmacist
      supply responsible for 11% of supplies during the pandemic years (2009-10) versus
      27% and 31% during 2007 and 2008, respectively. Pharmacist-supplied oseltamivir
      did not appear to be associated with the development of resistance, with
      identified likely stockpiling or with a decline in influenza immunization.
      Pharmacist supplies largely matched the timing of influenza in the community and
      peaked in June 2009, as did prescription supplies. CONCLUSIONS: Five years of non
      prescription oseltamivir in NZ has resulted in no significant change in the
      development of resistance or rates of influenza immunization. Supplies remained
      modest and significant consumer stockpiling through pharmacist supply has not
      occurred, even during the influenza A(H1N1)pdm09 pandemic in 2009 and 2010.
      Pharmacists could be better utilized in ensuring fast distribution of antivirals
      to influenza sufferers during a pandemic.

PMID- 22949625
TI  - The emerging problem of linezolid-resistant Staphylococcus.
AB  - The oxazolidinone antibiotic linezolid has demonstrated potent antimicrobial
      activity against Gram-positive bacterial pathogens, including methicillin
      resistant staphylococci. This article systematically reviews the published
      literature for reports of linezolid-resistant Staphylococcus (LRS) infections to
      identify epidemiological, microbiological and clinical features for these
      infections. Linezolid remains active against >98% of Staphylococcus, with
      resistance identified in 0.05% of Staphylococcus aureus and 1.4% of coagulase
      negative Staphylococcus (CoNS). In all reported cases, patients were treated with
      linezolid prior to isolation of LRS, with mean times of 20.0 +/- 47.0 months for
      S. aureus and 11.0 +/- 8.0 days for CoNS. The most common mechanisms for
      linezolid resistance were mutation (G2576T) to the 23S rRNA (63.5% of LRSA and
      60.2% of LRCoNS) or the presence of a transmissible cfr ribosomal
      methyltransferase (54.5% of LRSA and 15.9% of LRCoNS). The emergence of linezolid
      resistance in Staphylococcus poses significant challenges to the clinical
      treatment of infections caused by these organisms, and in particular CoNS.

PMID- 22949626
TI  - Alterations in intestinal microbiota of elderly Irish subjects post-antibiotic
      therapy.
AB  - OBJECTIVES: The human intestinal microbiota composition alters naturally with
      age, but is unusually perturbed by antibiotic therapy. The impact of antibiotic
      therapy on the composition of the intestinal microbiota of a cross-section of
      elderly Irish subjects (n = 185, >= 65 years) was investigated, taking into
      consideration their residence location. METHODS: Forty-two of the 185 elderly
      subjects were treated with at least one antibiotic within 1 month prior to faecal
      microbiota profiling. The residence locations of the subjects varied from long
      term nursing care and rehabilitation wards to day hospitals and the community.
      RESULTS: Culture-dependent methods indicated that faecal Bifidobacterium spp.
      numbers were significantly reduced following antibiotic treatment (P = 0.004, 7
      fold reduction), while levels of Lactobacillus spp. and Enterobacteriaceae were
      unaffected. The largest decrease in Bifidobacterium spp. numbers was linked to
      the administration of nucleic acid synthesis inhibitors (P = 0.004, 23-fold
      reduction). Microbiota profiling revealed a significant compositional change
      across nine genera following antibiotic therapy, including a relative increase in
      Lactobacillus spp. (P = 0.031), as well as a decrease in the number of genera
      identified in the antibiotic-treated subjects (n = 58), when compared with
      untreated subjects (n = 79). More alterations in the intestinal microbiota were
      observed post-nucleic acid synthesis inhibitor therapy, most notably a decrease
      in relative Faecalibacterium spp. numbers (P < 0.001). CONCLUSIONS: The impact of
      antibiotic therapy on the intestinal microbiota in the elderly should be
      considered for long-term health effects, and differential susceptibility may
      require the development of products (e.g. prebiotics and probiotics) for at-risk
      subjects.

PMID- 22949627
TI  - Reversible disulfide formation of the glutamate carboxypeptidase II inhibitor
      E2072 results in prolonged systemic exposures in vivo.
AB  - E2072 [(3-2-mercaptoethyl)biphenyl-2,3'-dicarboxylic acid] is a novel, potent and
      selective thiol-based glutamate carboxypeptidase II (GCP-II) inhibitor that has
      shown robust analgesic and neuroprotective efficacy in preclinical models of
      neuropathic pain and chemotherapy-induced peripheral neuropathy. For the first
      time, we describe the drug metabolism and pharmacokinetic profile of E2072 in
      rodents and primates. Intravenously administered E2072 was found to exhibit an
      unexpectedly long terminal half-life (105 +/- 40 h) in rats. The long half-life
      was found to be the result of its ability to rapidly form reversible homo- and
      possibly heterodisulfides that served as a continuous E2072 depot. The half-life
      of reversible homodisulfides was 208 +/- 81 h. In further support, direct
      intravenous administration of the E2072-homodisulfide in rats resulted in the
      formation of E2072, with both E2072 and its disulfide detected in plasma up to 7
      days after dose. The observed long exposures were consistent with the sustained
      efficacy of E2072 in rodent pain models for several days after dose cessation. It
      is noteworthy that a shorter t(1/2) of E2072 (23.0 +/- 1.2 h) and its
      homodisulfide (21.0 +/- 0.95 h) was observed in primates, indicating interspecies
      differences in its disposition. In addition, E2072 was found to be orally
      available with an absolute bioavailability of ~30% in rats and ~39% in monkeys. A
      tissue distribution study of E2072 and its homodisulfide in rats showed good
      tissue penetration, particularly in sciatic nerve, the presumed site of action
      for treatment of neuropathy. Metabolic stability and the correlation between
      pharmacokinetic profile and pharmacological efficacy support the use of this GCP
      II inhibitor in the clinic.

PMID- 22949629
TI  - Reported loneliness rather than social isolation is a risk factor for 10-year
      mortality in older men.

PMID- 22949628
TI  - Preferred binding orientations of phenacetin in CYP1A1 and CYP1A2 are associated
      with isoform-selective metabolism.
AB  - Human cytochromes P450 1A1 and 1A2 play important roles in drug metabolism and
      chemical carcinogenesis. Although these two enzymes share high sequence identity,
      they display different substrate specificities and inhibitor susceptibilities. In
      the present studies, we investigated the structural basis for these differences
      with phenacetin as a probe using a number of complementary approaches, such as
      enzyme kinetics, stoichiometric assays, NMR, and molecular modeling. Kinetic and
      stoichiometric analyses revealed that substrate specificity (k(cat)/K(m)) of
      CYP1A2 was approximately 18-fold greater than that of CYP1A1, as expected.
      Moreover, despite higher H2O2 production, the coupling efficiency of reducing
      equivalents to acetaminophen formation in CYP1A2 was tighter than that in CYP1A1.
      CYP1A1, in contrast to CYP1A2, displayed much higher uncoupling, producing more
      water. The subsequent NMR longitudinal (T1) relaxation studies with the substrate
      phenacetin and its product acetaminophen showed that both compounds displayed
      similar binding orientations within the active site of CYP1A1 and CYP1A2.
      However, the distance between the OCH2 protons of the ethoxy group (site of
      phenacetin O-deethylation) and the heme iron was 1.5 A shorter in CYP1A2 than in
      CYP1A1. The NMR findings are thus consistent with our kinetic and stoichiometric
      results, providing a likely molecular basis for more efficient metabolism of
      phenacetin by CYP1A2.

PMID- 22949630
TI  - Following self-harm, there are shared and differing risk factors for subsequent
      suicide death or accidental death.

PMID- 22949631
TI  - Biased inheritance of the protein PatN frees vegetative cells to initiate
      patterned heterocyst differentiation.
AB  - Heterocysts, cells specialized for nitrogen fixation in certain filamentous
      cyanobacteria, appear singly in a nonrandom spacing pattern along the chain of
      vegetative cells. A two-stage, biased initiation and competitive resolution model
      has been proposed to explain the establishment of this spacing pattern. There is
      substantial evidence that competitive resolution of a subset of cells initiating
      differentiation occurs by interactions between a self-enhancing activator
      protein, HetR, and a diffusible pentapeptide inhibitor PatS-5 (RGSGR). Results
      presented here show that the absence of a unique membrane protein, PatN, in
      Nostoc punctiforme strain ATCC 29133 leads to a threefold increase in heterocyst
      frequency and a fourfold decrease in the vegetative cell interval between
      heterocysts. A PatN-GFP translational fusion shows a pattern of biased
      inheritance in daughter vegetative cells of ammonium-grown cultures. Inactivation
      of another heterocyst patterning gene, patA, is epistatic to inactivation of
      patN, and transcription of patA increases in a patN-deletion strain, implying
      that patN may function by modulating levels of patA. The presence of PatN is
      hypothesized to decrease the competency of a vegetative cell to initiate
      heterocyst differentiation, and the cellular concentration of PatN is dependent
      on cell division that results in cells transiently depleted of PatN. We suggest
      that biased inheritance of cell-fate determinants is a phylogenetic domain
      spanning paradigm in the development of biological patterns.

PMID- 22949632
TI  - Assistive listening devices drive neuroplasticity in children with dyslexia.
AB  - Children with dyslexia often exhibit increased variability in sensory and
      cognitive aspects of hearing relative to typically developing peers. Assistive
      listening devices (classroom FM systems) may reduce auditory processing
      variability by enhancing acoustic clarity and attention. We assessed the impact
      of classroom FM system use for 1 year on auditory neurophysiology and reading
      skills in children with dyslexia. FM system use reduced the variability of
      subcortical responses to sound, and this improvement was linked to concomitant
      increases in reading and phonological awareness. Moreover, response consistency
      before FM system use predicted gains in phonological awareness. A matched control
      group of children with dyslexia attending the same schools who did not use the FM
      system did not show these effects. Assistive listening devices can improve the
      neural representation of speech and impact reading-related skills by enhancing
      acoustic clarity and attention, reducing variability in auditory processing.

PMID- 22949633
TI  - Precursor-centric genome-mining approach for lasso peptide discovery.
AB  - Lasso peptides are a class of ribosomally synthesized posttranslationally
      modified natural products found in bacteria. Currently known lasso peptides have
      a diverse set of pharmacologically relevant activities, including inhibition of
      bacterial growth, receptor antagonism, and enzyme inhibition. The biosynthesis of
      lasso peptides is specified by a cluster of three genes encoding a precursor
      protein and two enzymes. Here we develop a unique genome-mining algorithm to
      identify lasso peptide gene clusters in prokaryotes. Our approach involves
      pattern matching to a small number of conserved amino acids in precursor
      proteins, and thus allows for a more global survey of lasso peptide gene clusters
      than does homology-based genome mining. Of more than 3,000 currently sequenced
      prokaryotic genomes, we found 76 organisms that are putative lasso peptide
      producers. These organisms span nine bacterial phyla and an archaeal phylum. To
      provide validation of the genome-mining method, we focused on a single lasso
      peptide predicted to be produced by the freshwater bacterium Asticcacaulis
      excentricus. Heterologous expression of an engineered, minimal gene cluster in
      Escherichia coli led to the production of a unique lasso peptide, astexin-1. At
      23 aa, astexin-1 is the largest lasso peptide isolated to date. It is also highly
      polar, in contrast to many lasso peptides that are primarily hydrophobic. Astexin
      1 has modest antimicrobial activity against its phylogenetic relative Caulobacter
      crescentus. The solution structure of astexin-1 was determined revealing a unique
      topology that is stabilized by hydrogen bonding between segments of the peptide.

PMID- 22949634
TI  - UTX regulates mesoderm differentiation of embryonic stem cells independent of
      H3K27 demethylase activity.
AB  - To investigate the role of histone H3K27 demethylase UTX in embryonic stem (ES)
      cell differentiation, we have generated UTX knockout (KO) and enzyme-dead knock
      in male ES cells. Deletion of the X-chromosome-encoded UTX gene in male ES cells
      markedly decreases expression of the paralogous UTY gene encoded by Y chromosome,
      but has no effect on global H3K27me3 level, Hox gene expression, or ES cell self
      renewal. However, UTX KO cells show severe defects in mesoderm differentiation
      and induction of Brachyury, a transcription factor essential for mesoderm
      development. Surprisingly, UTX regulates mesoderm differentiation and Brachyury
      expression independent of its enzymatic activity. UTY, which lacks detectable
      demethylase activity, compensates for the loss of UTX in regulating Brachyury
      expression. UTX and UTY bind directly to Brachyury promoter and are required for
      Wnt/beta-catenin signaling-induced Brachyury expression in ES cells.
      Interestingly, male UTX KO embryos express normal levels of UTY and survive until
      birth. In contrast, female UTX KO mice, which lack the UTY gene, show embryonic
      lethality before embryonic day 11.5. Female UTX KO embryos show severe defects in
      both Brachyury expression and embryonic development of mesoderm-derived posterior
      notochord, cardiac, and hematopoietic tissues. These results indicate that UTX
      controls mesoderm differentiation and Brachyury expression independent of H3K27
      demethylase activity, and suggest that UTX and UTY are functionally redundant in
      ES cell differentiation and early embryonic development.

PMID- 22949635
TI  - Wnt ligands signal in a cooperative manner to promote foregut organogenesis.
AB  - Endoderm-mesenchyme cross-talk is a central process in the development of foregut
      derived organs. How signaling pathways integrate the activity of multiple ligands
      to guide organ development is poorly understood. We show that two Wnt ligands,
      Wnt2 and Wnt7b, cooperatively induce Wnt signaling without affecting the
      stabilization of the Wnt canonical effector beta-catenin despite it being
      necessary for Wnt2-Wnt7b cooperativity. Wnt2-Wnt7b cooperation is specific for
      mesenchymal cell lineages and the combined loss of Wnt2 and Wnt7b leads to more
      severe developmental defects in the lung than loss of Wnt2 or Wnt7b alone. High
      throughput small-molecule screens and biochemical assays reveal that the Pdgf
      pathway is required for cooperative Wnt2-Wnt7b signaling. Inhibition of Pdgf
      signaling in cell culture reduces Wnt2-Wnt7b cooperative signaling. Moreover,
      inhibition of Pdgf signaling in lung explant cultures results in decreased Wnt
      signaling and lung smooth-muscle development. These data suggest a model in which
      Pdgf signaling potentiates Wnt2-Wnt7b signaling to promote high levels of Wnt
      activity in mesenchymal progenitors that is required for proper development of
      endoderm-derived organs, such as the lung.

PMID- 22949636
TI  - Role of genes linked to sporadic Alzheimer's disease risk in the production of
      beta-amyloid peptides.
AB  - Alzheimer's disease (AD) is characterized by the presence of toxic protein
      aggregates or plaques composed of the amyloid beta (Abeta) peptide. Various
      lengths of Abeta peptide are generated by proteolytic cleavages of the amyloid
      precursor protein (APP). Mutations in many familial AD-associated genes affect
      the production of the longer Abeta42 variant that preferentially accumulates in
      plaques. In the case of sporadic or late-onset AD, which accounts for greater
      than 95% of cases, several genes are implicated in increasing the risk, but
      whether they also cause the disease by altering amyloid levels is currently
      unknown. Through loss of function studies in a model cell line, here RNAi
      mediated silencing of several late onset AD genes affected Abeta levels is shown.
      However, unlike the genes underlying familial AD, late onset AD-susceptibility
      genes do not specifically alter the Abeta42/40 ratios and suggest that these
      genes probably contribute to AD through distinct mechanisms.

PMID- 22949637
TI  - Molecular basis for recognition of methylated and specific DNA sequences by the
      zinc finger protein Kaiso.
AB  - Methylation of CpG dinucleotides in DNA is a common epigenetic modification in
      eukaryotes that plays a central role in maintenance of genome stability, gene
      silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional
      Cys(2)His(2) zinc finger protein implicated in tumor-cell proliferation, binds to
      both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif
      (TCCTGCNA) and represses transcription by recruiting chromatin remodeling
      corepression machinery to target genes. Here we report structures of the Kaiso
      zinc finger DNA-binding domain in complex with its nonmethylated, sequence
      specific DNA target (KBS) and with a symmetrically methylated DNA sequence
      derived from the promoter region of E-cadherin. Recognition of specific bases in
      the major groove of the core KBS and mCpG sites is accomplished through both
      classical and methyl CH...O hydrogen-bonding interactions with residues in the
      first two zinc fingers, whereas residues in the C-terminal extension following
      the third zinc finger bind in the opposing minor groove and are required for high
      affinity binding. The C-terminal region is disordered in the free protein and
      adopts an ordered structure upon binding to DNA. The structures of these Kaiso
      complexes provide insights into the mechanism by which a zinc finger protein can
      recognize mCpG sites as well as a specific, nonmethylated regulatory DNA
      sequence.

PMID- 22949638
TI  - Energetics of life on the deep seafloor.
AB  - With frigid temperatures and virtually no in situ productivity, the deep oceans,
      Earth's largest ecosystem, are especially energy-deprived systems. Our knowledge
      of the effects of this energy limitation on all levels of biological organization
      is very incomplete. Here, we use the Metabolic Theory of Ecology to examine the
      relative roles of carbon flux and temperature in influencing metabolic rate,
      growth rate, lifespan, body size, abundance, biomass, and biodiversity for life
      on the deep seafloor. We show that the relative impacts of thermal and chemical
      energy change across organizational scales. Results suggest that individual
      metabolic rates, growth, and turnover proceed as quickly as temperature
      influenced biochemical kinetics allow but that chemical energy limits higher
      order community structure and function. Understanding deep-sea energetics is a
      pressing problem because of accelerating climate change and the general lack of
      environmental regulatory policy for the deep oceans.

PMID- 22949639
TI  - The meaning of default options for potential organ donors.
AB  - Rates of participation in organ donation programs are known to be powerfully
      influenced by the relevant default policy in effect ("opt-in" vs. "opt-out").
      Three studies provide evidence that this difference in participation may occur in
      part because the requirement to opt-in or opt-out results in large differences in
      the meaning that individuals attach to participation. American participants in
      Study 1 rated participation as a significantly more substantial action when
      agreement was purportedly obtained under opt-in rather than opt-out conditions,
      and nonagreement as a greater abrogation of responsibility when that decision was
      made under opt-out rather than under opt-in conditions. Study 2 replicated these
      findings with respondents who live in Germany, which employs an opt-in donation
      policy, and in Austria, which has an opt-out policy. Study 3 required American
      participants to rate various actions that differ in the effort and self-sacrifice
      they demand. As predicted, the placement of organ donation on the resulting
      multidimensional scaling dimension differed significantly depending on whether it
      purportedly was made in an opt-in country (where it was considered roughly akin
      to giving away half of one's wealth to charity upon one's death) or an opt-out
      country (where it fell between letting others get ahead of one in line and
      volunteering some time to help the poor). We discuss the relationship between
      this change of meaning account and two other mechanisms-behavioral inertia and
      implicit norms-that we believe underlie the default effect in decision making and
      other effects of policies designed to influence decision-makers.

PMID- 22949640
TI  - Fusion activation by a headless parainfluenza virus 5 hemagglutinin-neuraminidase
      stalk suggests a modular mechanism for triggering.
AB  - The Paramyxoviridae family of enveloped viruses enters cells through the
      concerted action of two viral glycoproteins. The receptor-binding protein,
      hemagglutinin-neuraminidase (HN), H, or G, binds its cellular receptor and
      activates the fusion protein, F, which, through an extensive refolding event,
      brings viral and cellular membranes together, mediating virus-cell fusion.
      However, the underlying mechanism of F activation on receptor engagement remains
      unclear. Current hypotheses propose conformational changes in HN, H, or G
      propagating from the receptor-binding site in the HN, H, or G globular head to
      the F-interacting stalk region. We provide evidence that the receptor-binding
      globular head domain of the paramyxovirus parainfluenza virus 5 HN protein is
      entirely dispensable for F activation. Considering together the crystal
      structures of HN from different paramyxoviruses, varying energy requirements for
      fusion activation, F activation involving the parainfluenza virus 5 HN stalk
      domain, and properties of a chimeric paramyxovirus HN protein, we propose a
      simple model for the activation of paramyxovirus fusion.

PMID- 22949641
TI  - Self-regulation of the head-inducing properties of the Spemann organizer.
AB  - The Spemann organizer stands out from other signaling centers of the embryo
      because of its broad patterning effects. It defines development along the
      anteroposterior and dorsoventral axes of the vertebrate body, mainly by secreting
      antagonists of growth factors. Qualitative models proposed more than a decade ago
      explain the organizer's region-specific inductions (i.e., head and trunk) as the
      result of different combinations of antagonists. For example, head induction is
      mediated by extracellular inhibition of Wnt, BMP, and Nodal ligands. However,
      little is known about how the levels of these antagonists become harmonized with
      those of their targets and with the factors initially responsible for germ layers
      and organizer formation, including Nodal itself. Here we show that key
      ingredients of the head-organizer development, namely Nodal ligands, Nodal
      antagonists, and ADMP ligands reciprocally adjust each other's strength and range
      of activity by a self-regulating network of interlocked feedback and feedforward
      loops. A key element in this cross-talk is the limited availability of ACVR2a,
      for which Nodal and ADMP must compete. By trapping Nodal extracellularly, the
      Nodal antagonists Cerberus and Lefty are permissive for ADMP activity. The system
      self-regulates because ADMP/ACVR2a/Smad1 signaling in turn represses the
      expression of the Nodal antagonists, reestablishing the equilibrium. In sum, this
      work reveals an unprecedented set of interactions operating within the organizer
      that is critical for embryonic patterning.

PMID- 22949642
TI  - Coexistence between wildlife and humans at fine spatial scales.
AB  - Many wildlife species face imminent extinction because of human impacts, and
      therefore, a prevailing belief is that some wildlife species, particularly large
      carnivores and ungulates, cannot coexist with people at fine spatial scales
      (i.e., cannot regularly use the exact same point locations). This belief provides
      rationale for various conservation programs, such as resettling human communities
      outside protected areas. However, quantitative information on the capacity and
      mechanisms for wildlife to coexist with humans at fine spatial scales is scarce.
      Such information is vital, because the world is becoming increasingly crowded.
      Here, we provide empirical information about the capacity and mechanisms for
      tigers (a globally endangered species) to coexist with humans at fine spatial
      scales inside and outside Nepal's Chitwan National Park, a flagship protected
      area for imperiled wildlife. Information obtained from field cameras in 2010 and
      2011 indicated that human presence (i.e., people on foot and vehicles) was
      ubiquitous and abundant throughout the study site; however, tiger density was
      also high. Surprisingly, even at a fine spatial scale (i.e., camera locations),
      tigers spatially overlapped with people on foot and vehicles in both years.
      However, in both years, tigers offset their temporal activity patterns to be much
      less active during the day when human activity peaked. In addition to temporal
      displacement, tiger-human coexistence was likely enhanced by abundant tiger prey
      and low levels of tiger poaching. Incorporating fine-scale spatial and temporal
      activity patterns into conservation plans can help address a major global
      challenge-meeting human needs while sustaining wildlife.

PMID- 22949643
TI  - Resistance of Australian Helicoverpa armigera to fenvalerate is due to the
      chimeric P450 enzyme CYP337B3.
AB  - Worldwide, increasing numbers of insects have evolved resistance to a wide range
      of pesticides, which hampers their control in the field and, therefore, threatens
      agriculture. Members of the carboxylesterase and cytochrome P450 monooxygenase
      superfamilies are prominent candidates to confer metabolic resistance to
      pyrethroid insecticides. Both carboxylesterases and P450 enzymes have been shown
      to be involved in pyrethroid resistance in Australian Helicoverpa armigera, the
      noctuid species possessing by far the most reported resistance cases worldwide.
      However, specific enzymes responsible for pyrethroid resistance in field
      populations of this species have not yet been identified. Here, we show that the
      resistance toward fenvalerate in an Australian strain of H. armigera is due to a
      unique P450 enzyme, CYP337B3, which arose from unequal crossing-over between two
      parental P450 genes, resulting in a chimeric enzyme. CYP337B3 is capable of
      metabolizing fenvalerate into 4'-hydroxyfenvalerate, which exhibits no toxic
      effect on susceptible larvae; enzymes from the parental P450 genes showed no
      detectable fenvalerate metabolism. Furthermore, a polymorphic H. armigera strain
      could be bred into a susceptible line possessing the parental genes CYP337B1 and
      CYP337B2 and a resistant line possessing only CYP337B3. The exclusive presence of
      CYP337B3 in resistant insects of this strain confers a 42-fold resistance to
      fenvalerate. Thus, in addition to previously documented genetic mechanisms of
      resistance, recombination can also generate selectively advantageous variants,
      such as this chimeric P450 enzyme with an altered substrate specificity leading
      to a potent resistance mechanism.

PMID- 22949644
TI  - Deficiency in TNFRSF13B (TACI) expands T-follicular helper and germinal center B
      cells via increased ICOS-ligand expression but impairs plasma cell survival.
AB  - Mutations in TNFRSF13B, better known as transmembrane activator and calcium
      modulator and cyclophilin ligand interactor (TACI), contribute to common variable
      immunodeficiency and autoimmunity in humans. How TACI regulates these two
      opposing conditions is unclear, however. TACI binds the cytokines BAFF and APRIL,
      and previous studies using gene KO mice indicated that loss of TACI affected only
      T-cell-independent antibody responses. Here we demonstrate that Taci(-/-) mice
      have expanded populations of T follicular helper (T(fh)) and germinal center (GC)
      B cells in their spleens when immunized with T-cell-dependent antigen. The
      increased numbers of T(fh) and GC B cells in Taci(-/-) mice are largely a result
      of up-regulation of inducible costimulator (ICOS) ligand on TACI-deficient B
      cells, given that ablation of one copy of the Icosl allele restores normal levels
      of T(fh) and GC B cells in Taci(-/-) mice. Interestingly, despite the presence of
      increased T(fh) and antigen-specific B cells, immunized Taci(-/-) mice
      demonstrate defective antigen-specific antibody responses resulting from
      significantly reduced numbers of antibody-secreting cells (ASCs). This effect is
      attributed to the failure to down-regulate the proapoptotic molecule BIM in Taci(
      /-) plasma cells. Ablation of BIM could rescue ASC formation in Taci(-/-) mice,
      suggesting that TACI is more important for the survival of plasma cells than for
      the differentiation of these cells. Thus, our data reveal dual roles for TACI in
      B-cell terminal differentiation. On one hand, TACI modulates ICOS ligand
      expression and thereby limits the size of T(fh) and GC B-cell compartments and
      prevents autoimmunity. On the other hand, it regulates the survival of ASCs and
      plays an important role in humoral immunity.

PMID- 22949645
TI  - Structural basis for activation of the complement system by component C4
      cleavage.
AB  - An essential aspect of innate immunity is recognition of molecular patterns on
      the surface of pathogens or altered self through the lectin and classical
      pathways, two of the three well-established activation pathways of the complement
      system. This recognition causes activation of the MASP-2 or the C1s serine
      proteases followed by cleavage of the protein C4. Here we present the crystal
      structures of the 203-kDa human C4 and the 245-kDa C4.MASP-2 substrate.enzyme
      complex. When C4 binds to MASP-2, substantial conformational changes in C4 are
      induced, and its scissile bond region becomes ordered and inserted into the
      protease catalytic site in a manner canonical to serine proteases. In MASP-2, an
      exosite located within the CCP domains recognizes the C4 C345C domain 60 A from
      the scissile bond. Mutations in C4 and MASP-2 residues at the C345C-CCP interface
      inhibit the intermolecular interaction and C4 cleavage. The possible assembly of
      the huge in vivo enzyme-substrate complex consisting of glycan-bound mannan
      binding lectin, MASP-2, and C4 is discussed. Our own and prior functional data
      suggest that C1s in the classical pathway of complement activated by, e.g.,
      antigen-antibody complexes, also recognizes the C4 C345C domain through a CCP
      exosite. Our results provide a unified structural framework for understanding the
      early and essential step of C4 cleavage in the elimination of pathogens and
      altered self through two major pathways of complement activation.

PMID- 22949646
TI  - History of expansion and anthropogenic collapse in a top marine predator of the
      Black Sea estimated from genetic data.
AB  - Two major ecological transitions marked the history of the Black Sea after the
      last Ice Age. The first was the postglacial transition from a brackish-water to a
      marine ecosystem dominated by porpoises and dolphins once this basin was
      reconnected back to the Mediterranean Sea (ca. 8,000 y B.P.). The second occurred
      during the past decades, when overfishing and hunting activities brought these
      predators close to extinction, having a deep impact on the structure and dynamics
      of the ecosystem. Estimating the extent of this decimation is essential for
      characterizing this ecosystem's dynamics and for formulating restoration plans.
      However, this extent is poorly documented in historical records. We addressed
      this issue for one of the main Black Sea predators, the harbor porpoise, using a
      population genetics approach. Analyzing its genetic diversity using an
      approximate Bayesian computation approach, we show that only a demographic
      expansion (at most 5,000 y ago) followed by a contemporaneous population collapse
      can explain the observed genetic data. We demonstrate that both the postglacial
      settlement of harbor porpoises in the Black Sea and the recent anthropogenic
      activities have left a clear footprint on their genetic diversity. Specifically,
      we infer a strong population reduction (~90%) that occurred within the past 5
      decades, which can therefore clearly be related to the recent massive killing of
      small cetaceans and to the continuing incidental catches in commercial fisheries.
      Our study thus provides a quantitative assessment of these demographically
      catastrophic events, also showing that two separate historical events can be
      inferred from contemporary genetic data.

PMID- 22949647
TI  - Ultrastructural dynamics of proteins involved in endocytic budding.
AB  - Fluorescence live-cell imaging has temporally resolved the conserved choreography
      of more than 30 proteins involved in clathrin and actin-mediated endocytic
      budding from the plasma membrane. However, the resolution of these studies is
      insufficient to unveil how the endocytic machinery actually drives membrane
      deformation in vivo. In this study, we use quantitative immuno-EM to introduce
      the temporal dimension to the ultrastructural analysis of membrane budding and
      define changes in the topography of the lipid bilayer coupled to the dynamics of
      endocytic proteins with unprecedented spatiotemporal resolution. Using this
      approach, we frame the emergence of membrane curvature with respect to the
      recruitment of endocytic factors and show that constriction of the invaginations
      correlates with translocation of membrane-sculpting proteins. Furthermore, we
      show that initial bending of the plasma membrane is independent of actin and
      clathrin polymerization and precedes building of an actin cap branched by the
      Arp2/3 complex. Finally, our data indicate that constriction and additional
      elongation of the endocytic profiles require the mechanochemical activity of the
      myosins-I. Altogether, this work provides major insights into the molecular
      mechanisms driving membrane deformation in a cellular context.

PMID- 22949648
TI  - Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs
      378 and 378*.
AB  - Obesity and metabolic syndrome are associated with mitochondrial dysfunction and
      deranged regulation of metabolic genes. Peroxisome proliferator-activated
      receptor gamma coactivator 1beta (PGC-1beta) is a transcriptional coactivator
      that regulates metabolism and mitochondrial biogenesis through stimulation of
      nuclear hormone receptors and other transcription factors. We report that the PGC
      1beta gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which
      counterbalance the metabolic actions of PGC-1beta. Mice genetically lacking miR
      378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit
      enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of
      insulin-target tissues. Among the many targets of these miRNAs, carnitine O
      acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and
      MED13, a component of the Mediator complex that controls nuclear hormone receptor
      activity, are repressed by miR-378 and miR-378*, respectively, and are elevated
      in the livers of miR-378/378* KO mice. Consistent with these targets as
      contributors to the metabolic actions of miR-378 and miR-378*, previous studies
      have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and
      obesity. Our findings identify miR-378 and miR-378* as integral components of a
      regulatory circuit that functions under conditions of metabolic stress to control
      systemic energy homeostasis and the overall oxidative capacity of insulin target
      tissues. Thus, these miRNAs provide potential targets for pharmacologic
      intervention in obesity and metabolic syndrome.

PMID- 22949649
TI  - Persistent and reversible consequences of combat stress on the mesofrontal
      circuit and cognition.
AB  - Prolonged stress can have long-lasting effects on cognition. Animal models
      suggest that deficits in executive functioning could result from alterations
      within the mesofrontal circuit. We investigated this hypothesis in soldiers
      before and after deployment to Afghanistan and a control group using functional
      and diffusion tensor imaging. Combat stress reduced midbrain activity and
      integrity, which was associated to compromised sustained attention. Long-term
      follow-up showed that the functional and structural changes had normalized within
      1.5 y. In contrast, combat stress induced a persistent reduction in functional
      connectivity between the midbrain and prefrontal cortex. These results
      demonstrate that combat stress has adverse effects on the human mesofrontal
      circuit and suggests that these alterations are partially reversible.

PMID- 22949650
TI  - Loss of p63 and its microRNA-205 target results in enhanced cell migration and
      metastasis in prostate cancer.
AB  - p63 inhibits metastasis. Here, we show that p63 (both TAp63 and DeltaNp63
      isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR
      205 is essential for the inhibitory effects of p63 on markers of epithelial
      mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the
      inhibitory effect of p63 on EMT markers and cell migration is reverted by anti
      miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell
      migration, in a cell line expressing endogenous mutated p53, can be abrogated by
      pre-miR-205 or silencing of mutated p53. In accordance with this in vitro data,
      DeltaNp63 or miR-205 significantly inhibits the incidence of lung metastasis in
      vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR
      205 axis were absent in metastases or colonized lymph nodes in a set of 218 human
      prostate cancer samples. This was confirmed in an independent clinical data set
      of 281 patients. Loss of this axis was associated with higher Gleason scores, an
      increased likelihood of metastatic and infiltration events, and worse prognosis.
      These data suggest that p63/miR-205 may be a useful clinical predictor of
      metastatic behavior in prostate cancer.

PMID- 22949651
TI  - Evidence for additive and interaction effects of host genotype and infection in
      malaria.
AB  - The host mechanisms responsible for protection against malaria remain poorly
      understood, with only a few protective genetic effects mapped in humans. Here, we
      characterize a host-specific genome-wide signature in whole-blood transcriptomes
      of Plasmodium falciparum-infected West African children and report a
      demonstration of genotype-by-infection interactions in vivo. Several associations
      involve transcripts sensitive to infection and implicate complement system,
      antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1,
      FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that
      validated a genome-wide association candidate gene (SCO1), implicating binding
      variation within a noncoding regulatory element. Gene expression profiles in mice
      infected with Plasmodium chabaudi revealed and validated similar responses and
      highlighted specific pathways and genes that are likely important responders in
      both hosts. These results suggest that host variation and its interplay with
      infection affect children's ability to cope with infection and suggest a
      polygenic model mounted at the transcriptional level for susceptibility.

PMID- 22949652
TI  - In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts.
AB  - In embryonic development, the pancreas and liver share developmental history up
      to the stage of bud formation. Therefore, we postulated that direct reprogramming
      of liver to pancreatic cells can occur when suitable transcription factors are
      overexpressed. Using a polycistronic vector we misexpress Pdx1, Ngn3, and MafA in
      the livers of NOD-SCID mice rendered diabetic by treatment with streptozotocin
      (STZ). The diabetes is relieved long term. Many ectopic duct-like structures
      appear that express a variety of beta-cell markers, including dense core granules
      visible by electron microscopy (EM). Use of a vector also expressing GFP shows
      that the ducts persist long after the viral gene expression has ceased,
      indicating that this is a true irreversible cell reprogramming event. We have
      recovered the insulin(+) cells by cell sorting and shown that they display
      glucose-sensitive insulin secretion. The early formed insulin(+) cells can be
      seen to coexpress SOX9 and are also labeled in mice lineage labeled for Sox9
      expression. SOX9(+) cells are normally found associated with small bile ducts in
      the periportal region, indicating that the duct-like structures arise from this
      source. This work confirms that developmentally related cells can be reprogrammed
      by suitable transcription factors and also suggests a unique therapy for
      diabetes.

PMID- 22949653
TI  - Changes in water chemistry can disable plankton prey defenses.
AB  - The effectiveness of antipredator defenses is greatly influenced by the
      environment in which an organism lives. In aquatic ecosystems, the chemical
      composition of the water itself may play an important role in the outcome of
      predator-prey interactions by altering the ability of prey to detect predators or
      to implement defensive responses once the predator's presence is perceived. Here,
      we demonstrate that low calcium concentrations (<1.5 mg/L) that are found in many
      softwater lakes and ponds disable the ability of the water flea, Daphnia pulex to
      respond effectively to its predator, larvae of the phantom midge, Chaoborus
      americanus. This low-calcium environment prevents development of the prey's
      normal array of induced defenses, which include an increase in body size,
      formation of neck spines, and strengthening of the carapace. We estimate that
      this inability to access these otherwise effective defenses results in a 50-186%
      increase in the vulnerability of the smaller juvenile instars of Daphnia, the
      stages most susceptible to Chaoborus predation. Such a change likely contributes
      to the observed lack of success of daphniids in most low-calcium freshwater
      environments, and will speed the loss of these important zooplankton in lakes
      where calcium levels are in decline.

PMID- 22949654
TI  - The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding
      sites for water- and lipid-soluble substrates.
AB  - Bioenergy is efficiently produced in the mitochondria by the respiratory system
      consisting of complexes I-V. In various organisms, complex I can be replaced by
      the alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes the transfer
      of an electron from NADH via FAD to quinone, without proton pumping. The Ndi1
      protein from Saccharomyces cerevisiae is a monotopic membrane protein, directed
      to the matrix. A number of studies have investigated the potential use of Ndi1 as
      a therapeutic agent against complex I disorders, and the NDH-2 enzymes have
      emerged as potential therapeutic targets for treatments against the causative
      agents of malaria and tuberculosis. Here we present the crystal structures of
      Ndi1 in its substrate-free, NAD(+)- and ubiquinone- (UQ2) complexed states. The
      structures reveal that Ndi1 is a peripheral membrane protein forming an intimate
      dimer, in which packing of the monomeric units within the dimer creates an
      amphiphilic membrane-anchor domain structure. Crucially, the structures of the
      Ndi1-NAD(+) and Ndi1-UQ2 complexes show overlapping binding sites for the NAD(+)
      and quinone substrates.

PMID- 22949656
TI  - Lateralization of observational fear learning at the cortical but not thalamic
      level in mice.
AB  - Major cognitive and emotional faculties are dominantly lateralized in the human
      cerebral cortex. The mechanism of this lateralization has remained elusive owing
      to the inaccessibility of human brains to many experimental manipulations. In
      this study we demonstrate the hemispheric lateralization of observational fear
      learning in mice. Using unilateral inactivation as well as electrical stimulation
      of the anterior cingulate cortex (ACC), we show that observational fear learning
      is controlled by the right but not the left ACC. In contrast to the cortex,
      inactivation of either left or right thalamic nuclei, both of which are in
      reciprocal connection to ACC, induced similar impairment of this behavior. The
      data suggest that lateralization of negative emotions is an evolutionarily
      conserved trait and mainly involves cortical operations. Lateralization of the
      observational fear learning behavior in a rodent model will allow detailed
      analysis of cortical asymmetry in cognitive functions.

PMID- 22949655
TI  - Sex, prions, and plasmids in yeast.
AB  - Even deadly prions may be widespread in nature if they spread by infection faster
      than they kill off their hosts. The yeast prions [PSI+] and [URE3] (amyloids of
      Sup35p and Ure2p) were not found in 70 wild strains, while [PIN+] (amyloid of
      Rnq1p) was found in ~16% of the same population. Yeast prion infection occurs
      only by mating, balancing the detrimental effects of carrying the prion. We
      estimated the frequency of outcross mating as about 1% of mitotic doublings from
      the known detriment of carrying the 2-MUm DNA plasmid (~1%) and its frequency in
      wild populations (38/70). We also estimated the fraction of total matings that
      are outcross matings (~23-46%) from the fraction of heterozygosity at the highly
      polymorphic RNQ1 locus (~46%). These results show that the detriment of carrying
      even the mildest forms of [PSI+], [URE3], or [PIN+] is greater than 1%. We find
      that Rnq1p polymorphisms in wild strains include several premature stop codon
      alleles that cannot propagate [PIN+] from the reference allele and others with
      several small deletions and point mutations which show a small transmission
      barrier. Wild strains carrying [PIN+] are far more likely to be heterozygous at
      RNQ1 and other loci than are [pin-] strains, probably reflecting its being a
      sexually transmitted disease. Because sequence differences are known to block
      prion propagation or ameliorate its pathogenic effects, we hypothesize that
      polymorphism of RNQ1 was selected to protect cells from detrimental effects of
      the [PIN+] prion.

PMID- 22949657
TI  - TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst
      during infection.
AB  - Phagocytosis and oxidative burst are two major effector arms of innate immunity.
      Although it is known that both are activated by Toll-like receptors (TLRs) and
      Rac GTPases, how their strengths are controlled in quiescent and TLR-activated
      cells is not clear. We report here that TIPE2 (TNFAIP8L2) serves as a negative
      regulator of innate immunity by linking TLRs to Rac. TLRs control the expression
      levels of TIPE2, which in turn dictates the strengths of phagocytosis and
      oxidative burst by binding to and blocking Rac GTPases. Consequently, TIPE2
      knockout cells have enhanced phagocytic and bactericidal activities and TIPE2
      knockout mice are resistant to bacterial infection. Thus, TIPE2 sets the
      strengths of phagocytosis and oxidative burst and may be targeted to effectively
      control infections.

PMID- 22949658
TI  - Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein
      activity and improves drug delivery to the brain.
AB  - P-glycoprotein, an ATP-driven drug efflux pump, is a major obstacle to the
      delivery of small-molecule drugs across the blood-brain barrier and into the CNS.
      Here we test a unique signaling-based strategy to overcome this obstacle. We used
      a confocal microscopy-based assay with isolated rat brain capillaries to map a
      signaling pathway that within minutes abolishes P-glycoprotein transport activity
      without altering transporter protein expression or tight junction permeability.
      This pathway encompasses elements of proinflammatory- (TNF-alpha) and
      sphingolipid-based signaling. Critical to this pathway was signaling through
      sphingosine-1-phosphate receptor 1 (S1PR1). In brain capillaries, S1P acted
      through S1PR1 to rapidly and reversibly reduce P-glycoprotein transport activity.
      Sphingosine reduced transport by a sphingosine kinase-dependent mechanism.
      Importantly, fingolimod (FTY720), a S1P analog recently approved for treatment of
      multiple sclerosis, also rapidly reduced P-glycoprotein activity; similar effects
      were found with the active, phosphorylated metabolite (FTY720P). We validated
      these findings in vivo using in situ brain perfusion in rats. Administration of
      S1P, FTY720, or FTY729P increased brain uptake of three radiolabeled P
      glycoprotein substrates, (3)H-verapamil (threefold increase), (3)H-loperamide
      (fivefold increase), and (3)H-paclitaxel (fivefold increase); blocking S1PR1
      abolished this effect. Tight junctional permeability, measured as brain (14)C
      sucrose accumulation, was not altered. Therefore, targeting signaling through
      S1PR1 at the blood-brain barrier with the sphingolipid-based drugs, FTY720 or
      FTY720P, can rapidly and reversibly reduce basal P-glycoprotein activity and thus
      improve delivery of small-molecule therapeutics to the brain.

PMID- 22949659
TI  - Epistasis dominates the genetic architecture of Drosophila quantitative traits.
AB  - Epistasis-nonlinear genetic interactions between polymorphic loci-is the genetic
      basis of canalization and speciation, and epistatic interactions can be used to
      infer genetic networks affecting quantitative traits. However, the role that
      epistasis plays in the genetic architecture of quantitative traits is
      controversial. Here, we compared the genetic architecture of three Drosophila
      life history traits in the sequenced inbred lines of the Drosophila melanogaster
      Genetic Reference Panel (DGRP) and a large outbred, advanced intercross
      population derived from 40 DGRP lines (Flyland). We assessed allele frequency
      changes between pools of individuals at the extremes of the distribution for each
      trait in the Flyland population by deep DNA sequencing. The genetic architecture
      of all traits was highly polygenic in both analyses. Surprisingly, none of the
      SNPs associated with the traits in Flyland replicated in the DGRP and vice versa.
      However, the majority of these SNPs participated in at least one epistatic
      interaction in the DGRP. Despite apparent additive effects at largely distinct
      loci in the two populations, the epistatic interactions perturbed common,
      biologically plausible, and highly connected genetic networks. Our analysis
      underscores the importance of epistasis as a principal factor that determines
      variation for quantitative traits and provides a means to uncover genetic
      networks affecting these traits. Knowledge of epistatic networks will contribute
      to our understanding of the genetic basis of evolutionarily and clinically
      important traits and enhance predictive ability at an individualized level in
      medicine and agriculture.

PMID- 22949660
TI  - Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with
      regulation of virulence through cyclic dimeric guanosine monophosphate turnover.
AB  - Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum
      sensing (QS) signals in modulation of virulence and biofilm formation. Previous
      work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is
      involved in sensing and responding to DSF signals, but little is known in other
      microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family
      signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic
      dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR,
      which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same
      phenotypes as BDSF including swarming motility, biofilm formation, and virulence.
      In addition, the BDSF(-) mutant phenotypes could be rescued by in trans
      expression of RpfR, or its EAL domain that functions as a c-di-GMP
      phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high
      affinity and stimulates its phosphodiesterase activity through induction of
      allosteric conformational changes. Our work presents a unique and widely
      conserved DSF-family signal receptor that directly links the signal perception to
      c-di-GMP turnover in regulation of bacterial physiology.

PMID- 22949661
TI  - Alpha 1-antitrypsin reduces inflammation and enhances mouse pancreatic islet
      transplant survival.
AB  - The promise of islet cell transplantation cannot be fully realized in the absence
      of improvements in engraftment of resilient islets. The marginal mass of islets
      surviving the serial peritransplant insults may lead to exhaustion and thereby
      contribute to an unacceptably high rate of intermediate and long-term graft loss.
      Hence, we have studied the effects of treatment with alpha 1-antitrypsin (AAT) in
      a syngeneic nonautoimmune islet graft model. A marginal number of syngeneic mouse
      islets were transplanted into nonautoimmune diabetic hosts and islet function was
      analyzed in control and AAT treated hosts. In untreated controls, marginal mass
      islet transplants did not restore euglycemia. Outcomes were dramatically improved
      by short-term AAT treatment. Transcriptional profiling identified 1,184
      differentially expressed transcripts in AAT-treated hosts at 3 d
      posttransplantation. Systems-biology-based analysis revealed AAT down-regulated
      regulatory hubs formed by inflammation-related molecules (e.g., TNF-alpha, NF
      kappaB). The conclusions yielded by the systems-biology analysis were rigorously
      confirmed by QRT-PCR and immunohistology. These data suggest that short-term AAT
      treatment of human islet transplant recipients may be worthy of a clinical trial.

PMID- 22949663
TI  - Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and
      its implication for de novo design of nanomedicine.
AB  - Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth
      leading cause of cancer-related death in North America. Matrix metalloproteinases
      (MMPs) have long been targeted as a potential anticancer therapy because of their
      seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor
      survival and invasion. However, the inhibition specificity to MMPs and the
      molecular-level understanding of the inhibition mechanism remain largely
      unresolved. Here, we found that endohedral metallofullerenol Gd@C(82)(OH)(22) can
      successfully inhibit the neoplastic activity with experiments at animal, tissue,
      and cellular levels. Gd@C(82)(OH)(22) effectively blocks tumor growth in human
      pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also
      show Gd@C(82)(OH)(22) not only suppresses the expression of MMPs but also
      significantly reduces their activities. We then applied large-scale molecular
      dynamics simulations to illustrate the molecular mechanism by studying the
      Gd@C(82)(OH)(22)-MMP-9 interactions in atomic detail. Our data demonstrated that
      Gd@C(82)(OH)(22) inhibits MMP-9 mainly via an exocite interaction, whereas the
      well-known zinc catalytic site only plays a minimal role. Steered by nonspecific
      electrostatic, hydrophobic, and specific hydrogen-bonding interactions,
      Gd@C(82)(OH)(22) exhibits specific binding modes near the ligand-specificity loop
      S1', thereby inhibiting MMP-9 activity. Both the suppression of MMP expression
      and specific binding mode make Gd@C(82)(OH)(22) a potentially more effective
      nanomedicine for pancreatic cancer than traditional medicines, which usually
      target the proteolytic sites directly but fail in selective inhibition. Our
      findings provide insights for de novo design of nanomedicines for fatal diseases
      such as pancreatic cancer.

PMID- 22949662
TI  - Reproductive clonality of pathogens: a perspective on pathogenic viruses,
      bacteria, fungi, and parasitic protozoa.
AB  - We propose that clonal evolution in micropathogens be defined as restrained
      recombination on an evolutionary scale, with genetic exchange scarce enough to
      not break the prevalent pattern of clonal population structure, a definition
      already widely used for all kinds of pathogens, although not clearly formulated
      by many scientists and rejected by others. The two main manifestations of clonal
      evolution are strong linkage disequilibrium (LD) and widespread genetic
      clustering ("near-clading"). We hypothesize that this pattern is not mainly due
      to natural selection, but originates chiefly from in-built genetic properties of
      pathogens, which could be ancestral and could function as alternative allelic
      systems to recombination genes ("clonality/sexuality machinery") to escape
      recombinational load. The clonal framework of species of pathogens should be
      ascertained before any analysis of biomedical phenotypes (phylogenetic character
      mapping). In our opinion, this model provides a conceptual framework for the
      population genetics of any micropathogen.

PMID- 22949664
TI  - Vitamin D accelerates resolution of inflammatory responses during tuberculosis
      treatment.
AB  - Calcidiol, the major circulating metabolite of vitamin D, supports induction of
      pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates
      circulating calcidiol concentrations, and thus has a potential role in the
      prevention and treatment of infection. The immunomodulatory effects of
      administering vitamin D to humans with an infectious disease have not previously
      been reported. To characterize these effects, we conducted a detailed
      longitudinal study of circulating and antigen-stimulated immune responses in
      ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis
      who were randomized to receive adjunctive high-dose vitamin D or placebo in a
      clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D
      supplementation accelerated sputum smear conversion and enhanced treatment
      induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and
      hyperchemokinaemia. Administration of vitamin D also suppressed antigen
      stimulated proinflammatory cytokine responses, but attenuated the suppressive
      effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC
      chemokine ligand 5, and IFN-alpha. We demonstrate a previously unappreciated role
      for vitamin D supplementation in accelerating resolution of inflammatory
      responses during tuberculosis treatment. Our findings suggest a potential role
      for adjunctive vitamin D supplementation in the treatment of pulmonary infections
      to accelerate resolution of inflammatory responses associated with increased risk
      of mortality.

PMID- 22949665
TI  - Linking habitat mosaics and connectivity in a coral reef seascape.
AB  - Tropical marine ecosystems are under mounting anthropogenic pressure from
      overfishing and habitat destruction, leading to declines in their structure and
      function on a global scale. Although maintaining connectivity among habitats
      within a seascape is necessary for preserving population resistance and
      resilience, quantifying movements of individuals within seascapes remains
      challenging. Traditional methods of identifying and valuing potential coral reef
      fish nursery habitats are indirect, often relying on visual surveys of abundance
      and correlations of size and biomass among habitats. We used compound-specific
      stable isotope analyses to determine movement patterns of commercially important
      fish populations within a coral reef seascape. This approach allowed us to
      quantify the relative contributions of individuals from inshore nurseries to reef
      populations and identify migration corridors among important habitats. Our
      results provided direct measurements of remarkable migrations by juvenile snapper
      of over 30 km, between nurseries and reefs. We also found significant plasticity
      in juvenile nursery residency. Although a majority of individuals on coastal
      reefs had used seagrass nurseries as juveniles, many adults on oceanic reefs had
      settled directly into reef habitats. Moreover, seascape configuration played a
      critical but heretofore unrecognized role in determining connectivity among
      habitats. Finally, our approach provides key quantitative data necessary to
      estimate the value of distinctive habitats to ecosystem services provided by
      seascapes.

PMID- 22949666
TI  - Neural populations in human posteromedial cortex display opposing responses
      during memory and numerical processing.
AB  - Our understanding of the human default mode network derives primarily from
      neuroimaging data but its electrophysiological correlates remain largely
      unexplored. To address this limitation, we recorded intracranially from the human
      posteromedial cortex (PMC), a core structure of the default mode network, during
      various conditions of internally directed (e.g., autobiographical memory) as
      opposed to externally directed focus (e.g., arithmetic calculation). We observed
      late-onset (>400 ms) increases in broad high gamma-power (70-180 Hz) within PMC
      subregions during memory retrieval. High gamma-power was significantly reduced or
      absent when subjects retrieved self-referential semantic memories or responded to
      self-judgment statements, respectively. Conversely, a significant deactivation of
      high gamma-power was observed during arithmetic calculation, the duration of
      which correlated with reaction time at the signal-trial level. Strikingly, at
      each recording site, the magnitude of activation during episodic autobiographical
      memory retrieval predicted the degree of suppression during arithmetic
      calculation. These findings provide important anatomical and temporal details-at
      the neural population level-of PMC engagement during autobiographical memory
      retrieval and address how the same populations are actively suppressed during
      tasks, such as numerical processing, which require externally directed attention.

PMID- 22949667
TI  - Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs
      striatal neuron development.
AB  - Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are
      associated with the physiology of the striatum and the loss of its normal
      functioning under pathological conditions. The role of BDNF and its downstream
      signaling in regulating the development of the striatum has not been fully
      investigated, however. Here we report that ablation of Bdnf in both the cortex
      and substantia nigra depletes BDNF in the striatum, and leads to impaired
      striatal development, severe motor deficits, and postnatal lethality.
      Furthermore, striatal-specific ablation of TrkB, the gene encoding the high
      affinity receptor for BDNF, is sufficient to elicit an array of striatal
      developmental abnormalities, including decreased anatomical volume, smaller
      neuronal nucleus size, loss of dendritic spines, reduced enkephalin expression,
      diminished nigral dopaminergic projections, and severe deficits in striatal
      dopamine signaling through DARPP32. In addition, TrkB ablation in striatal
      neurons elicits a non-cell-autonomous reduction of tyrosine hydroxylase protein
      level in the axonal projections of substantia nigral dopaminergic neurons. Thus,
      our results establish an essential function for TrkB in regulating the
      development of striatal neurons.

PMID- 22949668
TI  - Monkeys benefit from reciprocity without the cognitive burden.
AB  - The debate about the origins of human prosociality has focused on the presence or
      absence of similar tendencies in other species, and, recently, attention has
      turned to the underlying mechanisms. We investigated whether direct reciprocity
      could promote prosocial behavior in brown capuchin monkeys (Cebus apella). Twelve
      capuchins tested in pairs could choose between two tokens, with one being
      "prosocial" in that it rewarded both individuals (i.e., 1/1), and the other being
      "selfish" in that it rewarded the chooser only (i.e., 1/0). Each monkey's choices
      with a familiar partner from their own group was compared with choices when
      paired with a partner from a different group. Capuchins were spontaneously
      prosocial, selecting the prosocial option at the same rate regardless of whether
      they were paired with an in-group or out-group partner. This indicates that
      interaction outside of the experimental setting played no role. When the paradigm
      was changed, such that both partners alternated making choices, prosocial
      preference significantly increased, leading to mutualistic payoffs. As no
      contingency could be detected between an individual's choice and their partner's
      previous choice, and choices occurred in rapid succession, reciprocity seemed of
      a relatively vague nature akin to mutualism. Having the partner receive a better
      reward than the chooser (i.e., 1/2) during the alternating condition increased
      the payoffs of mutual prosociality, and prosocial choice increased accordingly.
      The outcome of several controls made it hard to explain these results on the
      basis of reward distribution or learned preferences, and rather suggested that
      joint action promotes prosociality, resulting in so-called attitudinal
      reciprocity.

PMID- 22949669
TI  - Antibody-free, targeted mass-spectrometric approach for quantification of
      proteins at low picogram per milliliter levels in human plasma/serum.
AB  - Sensitive detection of low-abundance proteins in complex biological samples has
      typically been achieved by immunoassays that use antibodies specific to target
      proteins; however, de novo development of antibodies is associated with high
      costs, long development lead times, and high failure rates. To address these
      challenges, we developed an antibody-free strategy that involves PRISM (high
      pressure, high-resolution separations coupled with intelligent selection and
      multiplexing) for sensitive selected reaction monitoring (SRM)-based targeted
      protein quantification. The strategy capitalizes on high-resolution reversed
      phase liquid chromatographic separations for analyte enrichment, intelligent
      selection of target fractions via on-line SRM monitoring of internal standards,
      and fraction multiplexing before nano-liquid chromatography-SRM quantification.
      Application of this strategy to human plasma/serum demonstrated accurate and
      reproducible quantification of proteins at concentrations in the 50-100 pg/mL
      range, which represents a major advance in the sensitivity of targeted protein
      quantification without the need for specific-affinity reagents. Application to a
      set of clinical serum samples illustrated an excellent correlation between the
      results obtained from the PRISM-SRM assay and those from clinical immunoassay for
      the prostate-specific antigen level.

PMID- 22949670
TI  - Molecular analysis of the amphioxus frontal eye unravels the evolutionary origin
      of the retina and pigment cells of the vertebrate eye.
AB  - The origin of vertebrate eyes is still enigmatic. The "frontal eye" of amphioxus,
      our most primitive chordate relative, has long been recognized as a candidate
      precursor to the vertebrate eyes. However, the amphioxus frontal eye is composed
      of simple ciliated cells, unlike vertebrate rods and cones, which display more
      elaborate, surface-extended cilia. So far, the only evidence that the frontal eye
      indeed might be sensitive to light has been the presence of a ciliated putative
      sensory cell in the close vicinity of dark pigment cells. We set out to
      characterize the cell types of the amphioxus frontal eye molecularly, to test
      their possible relatedness to the cell types of vertebrate eyes. We show that the
      cells of the frontal eye specifically coexpress a combination of transcription
      factors and opsins typical of the vertebrate eye photoreceptors and an inhibitory
      Gi-type alpha subunit of the G protein, indicating an off-responding
      phototransductory cascade. Furthermore, the pigmented cells match the retinal
      pigmented epithelium in melanin content and regulatory signature. Finally, we
      reveal axonal projections of the frontal eye that resemble the basic photosensory
      motor circuit of the vertebrate forebrain. These results support homology of the
      amphioxus frontal eye and the vertebrate eyes and yield insights into their
      evolutionary origin.

PMID- 22949671
TI  - Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive
      immunity in bacteria.
AB  - Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR
      associated (Cas) systems provide adaptive immunity against viruses and plasmids
      in bacteria and archaea. The silencing of invading nucleic acids is executed by
      ribonucleoprotein complexes preloaded with small, interfering CRISPR RNAs
      (crRNAs) that act as guides for targeting and degradation of foreign nucleic
      acid. Here, we demonstrate that the Cas9-crRNA complex of the Streptococcus
      thermophilus CRISPR3/Cas system introduces in vitro a double-strand break at a
      specific site in DNA containing a sequence complementary to crRNA. DNA cleavage
      is executed by Cas9, which uses two distinct active sites, RuvC and HNH, to
      generate site-specific nicks on opposite DNA strands. Results demonstrate that
      the Cas9-crRNA complex functions as an RNA-guided endonuclease with RNA-directed
      target sequence recognition and protein-mediated DNA cleavage. These findings
      pave the way for engineering of universal programmable RNA-guided DNA
      endonucleases.

PMID- 22949672
TI  - Structural and mechanistic insights into guanylylation of RNA-splicing ligase
      RtcB joining RNA between 3'-terminal phosphate and 5'-OH.
AB  - The RtcB protein has recently been identified as a 3'-phosphate RNA ligase that
      directly joins an RNA strand ending with a 2',3'-cyclic phosphate to the 5'
      hydroxyl group of another RNA strand in a GTP/Mn(2+)-dependent reaction. Here, we
      report two crystal structures of Pyrococcus horikoshii RNA-splicing ligase RtcB
      in complex with Mn(2+) alone (RtcB/ Mn(2+)) and together with a covalently bound
      GMP (RtcB-GMP/Mn(2+)). The RtcB/ Mn(2+) structure (at 1.6 A resolution) shows two
      Mn(2+) ions at the active site, and an array of sulfate ions nearby that indicate
      the binding sites of the RNA phosphate backbone. The structure of the RtcB
      GMP/Mn(2+) complex (at 2.3 A resolution) reveals the detailed geometry of
      guanylylation of histidine 404. The critical roles of the key residues involved
      in the binding of the two Mn(2+) ions, the four sulfates, and GMP are validated
      in extensive mutagenesis and biochemical experiments, which also provide a
      thorough characterization for the three steps of the RtcB ligation pathway: (i)
      guanylylation of the enzyme, (ii) guanylyl-transfer to the RNA substrate, and
      (iii) overall ligation. These results demonstrate that the enzyme's substrate
      induced GTP binding site and the putative reactive RNA ends are in the vicinity
      of the binuclear Mn(2+) active center, which provides detailed insight into how
      the enzyme-bound GMP is tansferred to the 3'-phosphate of the RNA substrate for
      activation and subsequent nucleophilic attack by the 5'-hydroxyl of the second
      RNA substrate, resulting in the ligated product and release of GMP.

PMID- 22949673
TI  - Structure of the human MTERF4-NSUN4 protein complex that regulates mitochondrial
      ribosome biogenesis.
AB  - Proteins crucial for the respiratory chain are translated by the mitochondrial
      ribosome. Mitochondrial ribosome biogenesis is therefore critical for oxidative
      phosphorylation capacity and disturbances are known to cause human disease. This
      complex process is evolutionary conserved and involves several RNA processing and
      modification steps required for correct ribosomal RNA maturation. We recently
      showed that a member of the mitochondrial transcription termination factor
      (MTERF) family of proteins, MTERF4, recruits NSUN4, a 5-methylcytosine RNA
      methyltransferase, to the large ribosomal subunit in a process crucial for
      mitochondrial ribosome biogenesis. Here, we describe the 3D crystal structure of
      the human MTERF4-NSUN4 complex determined to 2.9 A resolution. MTERF4 is composed
      of structurally repeated MTERF-motifs that form a nucleic acid binding domain.
      NSUN4 lacks an N- or C-terminal extension that is commonly used for RNA
      recognition by related RNA methyltransferases. Instead, NSUN4 binds to the C
      terminus of MTERF4. A positively charged surface forms an RNA binding path from
      the concave to the convex side of MTERF4 and further along NSUN4 all of the way
      into the active site. This finding suggests that both subunits of the protein
      complex likely contribute to RNA recognition. The interface between MTERF4 and
      NSUN4 contains evolutionarily conserved polar and hydrophobic amino acids, and
      mutations that change these residues completely disrupt complex formation. This
      study provides a molecular explanation for MTERF4-dependent recruitment of NSUN4
      to ribosomal RNA and suggests a unique mechanism by which other members of the
      large MTERF-family of proteins can regulate ribosomal biogenesis.

PMID- 22949674
TI  - Activator protein 1 suppresses antitumor T-cell function via the induction of
      programmed death 1.
AB  - T cells play a critical role in tumor immunosurveillance by eliminating newly
      transformed somatic cells. However, tumor cell variants can escape from
      immunological control after immunoediting, leading to tumor progression. Whether
      and how T cells respond to tumor growth remain unclear. Here, we found that tumor
      infiltrating T cells exhibited persistently up-regulated expression of the
      activator protein 1 (AP-1) subunit c-Fos during tumor progression. The ectopic
      expression of c-Fos in T cells exacerbated tumor growth, whereas the T-cell
      specific deletion of c-Fos reduced tumor malignancy. This unexpected
      immunosuppressive effect of c-Fos was mediated through the induced expression of
      immune inhibitory receptor programmed death 1 (PD-1) via the direct binding of c
      Fos to the AP-1-binding site in the Pdcd1 (gene encoding PD-1) promoter. A knock
      in mutation of this binding site abrogated PD-1 induction, augmented antitumor T
      cell function and repressed tumor growth. Taken together, these findings indicate
      that T-cell c-Fos subsequently induces PD-1 expression in response to tumor
      progression and that disrupting such induction is essential for repression of
      tumor growth.

PMID- 22949675
TI  - Skeletal parasympathetic innervation communicates central IL-1 signals regulating
      bone mass accrual.
AB  - Bone mass accrual is a major determinant of skeletal mass, governed by bone
      remodeling, which consists of bone resorption by osteoclasts and bone formation
      by osteoblasts. Bone mass accrual is inhibited by sympathetic signaling centrally
      regulated through activation of receptors for serotonin, leptin, and ACh.
      However, skeletal activity of the parasympathetic nervous system (PSNS) has not
      been reported at the bone level. Here we report skeletal immune-positive fibers
      for the PSNS marker vesicular ACh transporter (VAChT). Pseudorabies virus
      inoculated into the distal femoral metaphysis is identifiable in the sacral
      intermediolateral cell column and central autonomic nucleus, demonstrating PSNS
      femoral innervation originating in the spinal cord. The PSNS neurotransmitter ACh
      targets nicotinic (nAChRs), but not muscarinic receptors in bone cells, affecting
      mainly osteoclasts. nAChR agonists up-regulate osteoclast apoptosis and restrain
      bone resorption. Mice deficient of the alpha(2)nAChR subunit have increased bone
      resorption and low bone mass. Silencing of the IL-1 receptor signaling in the
      central nervous system by brain-specific overexpression of the human IL-1
      receptor antagonist (hIL1ra(Ast)(+/+) mice) leads to very low skeletal VAChT
      expression and ACh levels. These mice also exhibit increased bone resorption and
      low bone mass. In WT but not in hIL1ra(Ast)(+/+) mice, the cholinergic ACh
      esterase inhibitor pyridostigmine increases ACh levels and bone mass apparently
      by inhibiting bone resorption. Taken together, these results identify a
      previously unexplored key central IL-1-parasympathetic-bone axis that antagonizes
      the skeletal sympathetic tone, thus potently favoring bone mass accrual.

PMID- 22949677
TI  - Ubiquity and quantitative significance of detoxification catabolism of
      chlorophyll associated with protistan herbivory.
AB  - Chlorophylls are essential components of the photosynthetic apparati that sustain
      all of the life forms that ultimately depend on solar energy. However, a drawback
      of the extraordinary photosensitizing efficiency of certain chlorophyll species
      is their ability to generate harmful singlet oxygen. Recent studies have
      clarified the catabolic processes involved in the detoxification of chlorophylls
      in land plants, but little is understood about these strategies in aquatic
      ecosystem. Here, we report that a variety of heterotrophic protists accumulate
      the chlorophyll a catabolite 13(2),17(3)-cyclopheophorbide a enol (cPPB-aE) after
      their ingestion of algae. This chlorophyll derivative is nonfluorescent in
      solution, and its inability to generate singlet oxygen in vitro qualifies it as a
      detoxified catabolite of chlorophyll a. Using a modified analytical method, we
      show that cPPB-aE is ubiquitous in aquatic environments, and it is often the
      major chlorophyll a derivative. Our findings suggest that cPPB-aE metabolism is
      one of the most important, widely distributed processes in aquatic ecosystems.
      Therefore, the herbivorous protists that convert chlorophyll a to cPPB-aE are
      suggested to play more significant roles in the modern oceanic carbon flux than
      was previously recognized, critically linking microscopic primary producers to
      the macroscopic food web and carbon sequestration in the ocean.

PMID- 22949678
TI  - Endogenous viral antigen processing generates peptide-specific MHC class I cell
      surface clusters.
AB  - Sensitivity is essential in CD8+ T-cell killing of virus-infected cells and tumor
      cells. Although the affinity of the T-cell receptor (TCR) for antigen is
      relatively low, the avidity of T cell-antigen-presenting cell interactions is
      greatly enhanced by increasing the valence of the interaction. It is known that
      TCRs cluster into protein islands after engaging their cognate antigen (peptides
      bound to MHC molecules). Here, we show that mouse K(b) class I molecules
      segregate into preformed, long-lasting (hours) clusters on the antigen-presenting
      cell surface based on their bound viral peptide. Peptide-specific K(b) clustering
      occurs when source antigens are expressed by vaccinia or vesicular stomatitis
      virus, either as proteasome-liberated precursors or free intracellular peptides.
      By contrast, K(b)-peptide complexes generated by incubating cells with synthetic
      peptides are extensively intermingled on the cell surface. Peptide-specific
      complex sorting is first detected in the Golgi complex, and compromised by
      removing the K(b) cytoplasmic tail. Peptide-specific clustering is associated
      with increased T-cell sensitivity: on a per-complex basis, endogenous SIINFEKL
      activates T cells more efficiently than synthetic SIINFEKL, and wild-type K(b)
      presents endogenous SIINFEKL more efficiently than tailless K(b). We propose that
      endogenous processing generates peptide-specific clusters of class I molecules to
      maximize the sensitivity and speed of T-cell immunosurveillance.

PMID- 22949679
TI  - Regulation of immunity and disease resistance by commensal microbes and chromatin
      modifications during zebrafish development.
AB  - How fish larvae are protected from infection before the maturation of adaptive
      immunity, a process which may take up to several weeks in most species, has long
      been a matter of speculation. Using a germ-free model, we show that colonization
      by commensals in newly hatched zebrafish primes neutrophils and induces several
      genes encoding proinflammatory and antiviral mediators, increasing the resistance
      of larvae to viral infection. Commensal microbe recognition was found to be
      mediated mainly through a TLR/MyD88 signaling pathway, and professional
      phagocytes were identified as the source of these immune mediators. However, the
      induction of proinflammatory and antiviral genes, but not of antimicrobial
      effector genes, also required the covalent modification of histone H3 at gene
      promoters. Interestingly, chromatin modifications were not altered by commensal
      microbes or hatching. Taken together, our results demonstrate that gene-specific
      chromatin modifications are associated with the protection of zebrafish larvae
      against infectious agents before adaptive immunity has developed and prevent
      pathologies associated with excessive inflammation during development.

PMID- 22949680
TI  - Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap
      junction transfer of GDP-L-fucose in Drosophila.
AB  - Notch (N) is a transmembrane receptor that mediates cell-cell interactions to
      determine many cell-fate decisions. N contains EGF-like repeats, many of which
      have an O-fucose glycan modification that regulates N-ligand binding. This
      modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose
      biosynthetic pathways are well understood, including the de novo pathway, which
      depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5
      epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied
      GDP-L-fucose and the molecular basis of such transportation have not been
      explored in depth. To address these points, we studied the genetic effects of
      mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these
      mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied
      intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not
      supplied through body fluids from different isolated organs, indicating that the
      intercellular distribution of GDP-L-fucose is restricted within a given organ.
      Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to
      support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like
      repeats. Our results indicate that intercellular delivery is a metabolic pathway
      for nucleotide sugars in live animals under certain circumstances.

PMID- 22949681
TI  - Models with a porpoise.

PMID- 22949682
TI  - Oncogenic mutations mimic and enhance dynamic events in the natural activation of
      phosphoinositide 3-kinase p110alpha (PIK3CA).
AB  - The p110alpha catalytic subunit (PIK3CA) is one of the most frequently mutated
      genes in cancer. We have examined the activation of the wild-type
      p110alpha/p85alpha and a spectrum of oncogenic mutants using hydrogen/deuterium
      exchange mass spectrometry (HDX-MS). We find that for the wild-type enzyme, the
      natural transition from an inactive cytosolic conformation to an activated form
      on membranes entails four distinct events. Analysis of oncogenic mutations shows
      that all up-regulate the enzyme by enhancing one or more of these dynamic events.
      We provide the first insight into the activation mechanism by mutations in the
      linker between the adapter-binding domain (ABD) and the Ras-binding domain (RBD)
      (G106V and G118D). These mutations, which are common in endometrial cancers,
      enhance two of the natural activation events: movement of the ABD and ABD-RBD
      linker relative to the rest of the catalytic subunit and breaking the C2-iSH2
      interface on binding membranes. C2 domain mutants (N345K and C420R) also mimic
      these events, even in the absence of membranes. A third event is breaking the
      nSH2-helical domain contact caused by phosphotyrosine-containing peptides binding
      to the enzyme, which is mimicked by a helical domain mutation (E545K).
      Interaction of the C lobe of the kinase domain with membranes is the fourth
      activation event, and is potentiated by kinase domain mutations (e.g., H1047R).
      All mutations increased lipid binding and basal activity, even mutants distant
      from the membrane surface. Our results elucidate a unifying mechanism in which
      diverse PIK3CA mutations stimulate lipid kinase activity by facilitating
      allosteric motions required for catalysis on membranes.

PMID- 22949683
TI  - AU-rich element-binding protein negatively regulates CCAAT enhancer-binding
      protein mRNA stability during long-term synaptic plasticity in Aplysia.
AB  - The consolidation of long-term memory for sensitization and synaptic facilitation
      in Aplysia requires synthesis of new mRNA including the immediate early gene
      Aplysia CCAAT enhancer-binding protein (ApC/EBP). After the rapid induction of
      ApC/EBP expression in response to repeated treatments of 5-hydroxytryptamine (5
      HT), ApC/EBP mRNA is temporarily expressed in sensory neurons of sensory-to-motor
      synapses. However, the molecular mechanism underlying the rapid degradation of
      ApC/EBP transcript is not known. Here, we cloned an AU-rich element (ARE)-binding
      protein, ApAUF1, which functions as a destabilizing factor for ApC/EBP mRNA.
      ApAUF1 was found to bind to the 3' UTR of ApC/EBP mRNA that contains AREs and
      subsequently reduces the expression of ApC/EBP 3' UTR-containing reporter genes.
      Moreover, overexpression of ApAUF1 inhibited the induction of ApC/EBP mRNA in
      sensory neurons and also impaired long-term facilitation of sensory-to-motor
      synapses by repetitive 5-HT treatments. These results provide evidence for a
      critical role of the posttranscriptional modification of ApC/EBP mRNA during the
      consolidation of synaptic plasticity.

PMID- 22949684
TI  - The changing conditions of zebrafish mutants.

PMID- 22949686
TI  - Direct substitution and assisted dissociation pathways for turning off
      transcription by a MerR-family metalloregulator.
AB  - Metalloregulators regulate transcription in response to metal ions. Many studies
      have provided insights into how transcription is activated upon metal binding by
      MerR-family metalloregulators. In contrast, how transcription is turned off after
      activation is unclear. Turning off transcription promptly is important, however,
      as the cells would not want to continue expressing metal resistance genes and
      thus waste energy after metal stress is relieved. Using single-molecule FRET
      measurements we studied the dynamic interactions of the copper efflux regulator
      (CueR), a Cu(+)-responsive MerR-family metalloregulator, with DNA. Besides
      quantifying its DNA binding and unbinding kinetics, we discovered that CueR
      spontaneously flips its binding orientation at the recognition site. CueR also
      has two different binding modes, corresponding to interactions with specific and
      nonspecific DNA sequences, which would facilitate recognition localization. Most
      strikingly, a CueR molecule coming from solution can directly substitute for a
      DNA-bound CueR or assist the dissociation of the incumbent CueR, both of which
      are unique examples for any DNA-binding protein. The kinetics of the direct
      protein substitution and assisted dissociation reactions indicate that these two
      unique processes can provide efficient pathways to replace a DNA-bound holo-CueR
      with apo-CueR, thus turning off transcription promptly and facilely.

PMID- 22949687
TI  - Coherence brightened laser source for atmospheric remote sensing.
AB  - We have studied coherent emission from ambient air and demonstrated efficient
      generation of laser-like beams directed both forward and backward with respect to
      a nanosecond ultraviolet pumping laser beam. The generated optical gain is a
      result of two-photon photolysis of atmospheric O(2), followed by two-photon
      excitation of atomic oxygen. We have analyzed the temporal shapes of the emitted
      pulses and have observed very short duration intensity spikes as well as a large
      Rabi frequency that corresponds to the emitted field. Our results suggest that
      the emission process exhibits nonadiabatic atomic coherence, which is similar in
      nature to Dicke superradiance where atomic coherence is large and can be
      contrasted with ordinary lasing where atomic coherence is negligible. This atomic
      coherence in oxygen adds insight to the optical emission physics and holds
      promise for remote sensing techniques employing nonlinear spectroscopy.

PMID- 22949688
TI  - Recurrent slow slip event likely hastened by the 2011 Tohoku earthquake.
AB  - Slow slip events (SSEs) are another mode of fault deformation than the fast
      faulting of regular earthquakes. Such transient episodes have been observed at
      plate boundaries in a number of subduction zones around the globe. The SSEs near
      the Boso Peninsula, central Japan, are among the most documented SSEs, with the
      longest repeating history, of almost 30 y, and have a recurrence interval of 5 to
      7 y. A remarkable characteristic of the slow slip episodes is the accompanying
      earthquake swarm activity. Our stable, long-term seismic observations enable us
      to detect SSEs using the recorded earthquake catalog, by considering an
      earthquake swarm as a proxy for a slow slip episode. Six recurrent episodes are
      identified in this way since 1982. The average duration of the SSE
      interoccurrence interval is 68 mo; however, there are significant fluctuations
      from this mean. While a regular cycle can be explained using a simple physical
      model, the mechanisms that are responsible for the observed fluctuations are
      poorly known. Here we show that the latest SSE in the Boso Peninsula was likely
      hastened by the stress transfer from the March 11, 2011 great Tohoku earthquake.
      Moreover, a similar mechanism accounts for the delay of an SSE in 1990 by a
      nearby earthquake. The low stress buildups and drops during the SSE cycle can
      explain the strong sensitivity of these SSEs to stress transfer from external
      sources.

PMID- 22949689
TI  - Fluoride resistance and transport by riboswitch-controlled CLC antiporters.
AB  - A subclass of bacterial CLC anion-transporting proteins, phylogenetically distant
      from long-studied CLCs, was recently shown to be specifically up-regulated by F(
      ). We establish here that a set of randomly selected representatives from this
      "CLC(F)" clade protect Escherichia coli from F(-) toxicity, and that the purified
      proteins catalyze transport of F(-) in liposomes. Sequence alignments and
      membrane transport experiments using (19)F NMR, osmotic response assays, and
      planar lipid bilayer recordings reveal four mechanistic traits that set CLC(F)
      proteins apart from all other known CLCs. First, CLC(F)s lack conserved residues
      that form the anion binding site in canonical CLCs. Second, CLC(F)s exhibit high
      anion selectivity for F(-) over Cl(-). Third, at a residue thought to distinguish
      CLC channels and transporters, CLC(F)s bear a channel-like valine rather than a
      transporter-like glutamate, and yet are F(-)/H(+) antiporters. Finally, F(-)/H(+)
      exchange occurs with 1:1 stoichiometry, in contrast to the usual value of 2:1.

PMID- 22949690
TI  - Direct observation of hydrogen atom dynamics and interactions by ultrahigh
      resolution neutron protein crystallography.
AB  - The 1.1 A, ultrahigh resolution neutron structure of hydrogen/deuterium (H/D)
      exchanged crambin is reported. Two hundred ninety-nine out of 315, or 94.9%, of
      the hydrogen atom positions in the protein have been experimentally derived and
      resolved through nuclear density maps. A number of unconventional interactions
      are clearly defined, including a potential O?H...pi interaction between a water
      molecule and the aromatic ring of residue Y44, as well as a number of potential
      C?H...O hydrogen bonds. Hydrogen bonding networks that are ambiguous in the 0.85
      A ultrahigh resolution X-ray structure can be resolved by accurate orientation of
      water molecules. Furthermore, the high resolution of the reported structure has
      allowed for the anisotropic description of 36 deuterium atoms in the protein. The
      visibility of hydrogen and deuterium atoms in the nuclear density maps is
      discussed in relation to the resolution of the neutron data.

PMID- 22949691
TI  - Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as
      revealed by combining FTIR and biomolecular simulations.
AB  - Members of the Ras superfamily regulate many cellular processes. They are down
      regulated by a GTPase reaction in which GTP is cleaved into GDP and P(i) by
      nucleophilic attack of a water molecule. Ras proteins accelerate GTP hydrolysis
      by a factor of 10(5) compared to GTP in water. GTPase-activating proteins (GAPs)
      accelerate hydrolysis by another factor of 10(5) compared to Ras alone. Oncogenic
      mutations in Ras and GAPs slow GTP hydrolysis and are a factor in many cancers.
      Here, we elucidate in detail how this remarkable catalysis is brought about. We
      refined the protein-bound GTP structure and protein-induced charge shifts within
      GTP beyond the current resolution of X-ray structural models by combining quantum
      mechanics and molecular mechanics simulations with time-resolved Fourier
      transform infrared spectroscopy. The simulations were validated by comparing
      experimental and theoretical IR difference spectra. The reactant structure of GTP
      is destabilized by Ras via a conformational change from a staggered to an
      eclipsed position of the nonbridging oxygen atoms of the gamma- relative to the
      beta-phosphates and the further rotation of the nonbridging oxygen atoms of alpha
      relative to the beta- and gamma-phosphates by GAP. Further, the gamma-phosphate
      becomes more positive although two of its oxygen atoms remain negative. This
      facilitates the nucleophilic attack by the water oxygen at the phosphate and
      proton transfer to the oxygen. Detailed changes in geometry and charge
      distribution in the ligand below the resolution of X-ray structure analysis are
      important for catalysis. Such high resolution appears crucial for the
      understanding of enzyme catalysis.

PMID- 22949692
TI  - Shaping acoustic fields as a toolset for microfluidic manipulations in diagnostic
      technologies.
AB  - Ultrasonics offers the possibility of developing sophisticated fluid manipulation
      tools in lab-on-a-chip technologies. Here we demonstrate the ability to shape
      ultrasonic fields by using phononic lattices, patterned on a disposable chip, to
      carry out the complex sequence of fluidic manipulations required to detect the
      rodent malaria parasite Plasmodium berghei in blood. To illustrate the different
      tools that are available to us, we used acoustic fields to produce the required
      rotational vortices that mechanically lyse both the red blood cells and the
      parasitic cells present in a drop of blood. This procedure was followed by the
      amplification of parasitic genomic sequences using different acoustic fields and
      frequencies to heat the sample and perform a real-time PCR amplification. The
      system does not require the use of lytic reagents nor enrichment steps, making it
      suitable for further integration into lab-on-a-chip point-of-care devices. This
      acoustic sample preparation and PCR enables us to detect ca. 30 parasites in a
      microliter-sized blood sample, which is the same order of magnitude in
      sensitivity as lab-based PCR tests. Unlike other lab-on-a-chip methods, where the
      sample moves through channels, here we use our ability to shape the acoustic
      fields in a frequency-dependent manner to provide different analytical functions.
      The methods also provide a clear route toward the integration of PCR to detect
      pathogens in a single handheld system.

PMID- 22949693
TI  - Sulfur isotopes of organic matter preserved in 3.45-billion-year-old
      stromatolites reveal microbial metabolism.
AB  - The 3.45-billion-year-old Strelley Pool Formation of Western Australia preserves
      stromatolites that are considered among the oldest evidence for life on Earth. In
      places of exceptional preservation, these stromatolites contain laminae rich in
      organic carbon, interpreted as the fossil remains of ancient microbial mats. To
      better understand the biogeochemistry of these rocks, we performed microscale in
      situ sulfur isotope measurements of the preserved organic sulfur, including both
      Delta(33)S and  . This approach allows us to tie physiological inference from
      isotope ratios directly to fossil biomass, providing a means to understand sulfur
      metabolism that is complimentary to, and independent from, inorganic proxies
      (e.g., pyrite). Delta(33)S values of the kerogen reveal mass-anomalous
      fractionations expected of the Archean sulfur cycle, whereas   values show large
      fractionations at very small spatial scales, including values below -150/00. We
      interpret these isotopic patterns as recording the process of sulfurization of
      organic matter by H(2)S in heterogeneous mat pore-waters influenced by
      respiratory S metabolism. Positive Delta(33)S anomalies suggest that
      disproportionation of elemental sulfur would have been a prominent microbial
      process in these communities.

PMID- 22949694
TI  - Stress imparted by the great 2004 Sumatra earthquake shut down transforms and
      activated rifts up to 400 km away in the Andaman Sea.
AB  - The origin and prevalence of triggered seismicity and remote aftershocks are
      under debate. As a result, they have been excluded from probabilistic seismic
      hazard assessment and aftershock hazard notices. The 2004 M = 9.2 Sumatra
      earthquake altered seismicity in the Andaman backarc rift-transform system. Here
      we show that over a 300-km-long largely transform section of the backarc, M>=4.5
      earthquakes stopped for five years, and over a 750-km-long backarc section, the
      rate of transform events dropped by two-thirds, while the rate of rift events
      increased eightfold. We compute the propagating dynamic stress wavefield and find
      the peak dynamic Coulomb stress is similar on the rifts and transforms. Long
      period dynamic stress amplitudes, which are thought to promote dynamic failure,
      are higher on the transforms than on the rifts, opposite to the observations. In
      contrast to the dynamic stress, we calculate that the mainshock brought the
      transform segments approximately 0.2 bar (0.02 MPa) farther from static Coulomb
      failure and the rift segments approximately 0.2 bar closer to static failure,
      consistent with the seismic observations. This accord means that changes in
      seismicity rate are sufficiently predictable to be included in post-mainshock
      hazard evaluations.

PMID- 22949695
TI  - Direct observation of a force-induced switch in the anisotropic mechanical
      unfolding pathway of a protein.
AB  - Many biological processes generate force, and proteins have evolved to resist and
      respond to tension along different force axes. Single-molecule force spectroscopy
      allows for molecular insight into the behavior of proteins under force and the
      mechanism of protein folding in general. Here, we have used src SH3 to
      investigate the effect of different pulling axes under the low-force regime
      afforded by an optical trap. We find that this small cooperatively folded protein
      shows an anisotropic response to force; the protein is more mechanically
      resistant to force applied along a longitudinal axis compared to force applied
      perpendicular to the terminal beta strand. In the longitudinal axis, we observe
      an unusual biphasic behavior revealing a force-induced switch in the unfolding
      mechanism suggesting the existence of two parallel unfolding pathways. A site
      specific variant can selectively affect one of these pathways. Thus, even this
      simple two-state protein demonstrates a complex mechanical unfolding trajectory,
      accessing multiple unfolding pathways under the low-force regime of the optical
      trap; the specific unfolding pathway depends on the perturbation axis and the
      applied force.

PMID- 22949696
TI  - Roll up nanowire battery from silicon chips.
AB  - Here we report an approach to roll out Li-ion battery components from silicon
      chips by a continuous and repeatable etch-infiltrate-peel cycle. Vertically
      aligned silicon nanowires etched from recycled silicon wafers are captured in a
      polymer matrix that operates as Li(+) gel-electrolyte and electrode separator and
      peeled off to make multiple battery devices out of a single wafer. Porous,
      electrically interconnected copper nanoshells are conformally deposited around
      the silicon nanowires to stabilize the electrodes over extended cycles and
      provide efficient current collection. Using the above developed process we
      demonstrate an operational full cell 3.4 V lithium-polymer silicon nanowire
      (LIPOSIL) battery which is mechanically flexible and scalable to large
      dimensions.

PMID- 22949697
TI  - Biodiversity tracks temperature over time.
AB  - The geographic distribution of life on Earth supports a general pattern of
      increase in biodiversity with increasing temperature. However, some previous
      analyses of the 540-million-year Phanerozoic fossil record found a contrary
      relationship, with paleodiversity declining when the planet warms. These
      contradictory findings are hard to reconcile theoretically. We analyze marine
      invertebrate biodiversity patterns for the Phanerozoic Eon while controlling for
      sampling effort. This control appears to reverse the temporal association between
      temperature and biodiversity, such that taxonomic richness increases, not
      decreases, with temperature. Increasing temperatures also predict extinction and
      origination rates, alongside other abiotic and biotic predictor variables. These
      results undermine previous reports of a negative biodiversity-temperature
      relationship through time, which we attribute to paleontological sampling biases.
      Our findings suggest a convergence of global scale macroevolutionary and
      macroecological patterns for the biodiversity-temperature relationship.

PMID- 22949698
TI  - Sensitization of ultra-long-range excited-state electron transfer by energy
      transfer in a polymerized film.
AB  - Distance-dependent energy transfer occurs from the Metal-to-Ligand Charge
      Transfer (MLCT) excited state Ru(bpy)3(2+*) to an anthracene-acrylate derivative
      (Acr-An) incorporated into the polymer network of a semirigid
      poly(ethyleneglycol)dimethacrylate monolith. Following excitation, Ru(bpy)3(2+*)
      to Acr-An triplet energy transfer occurs followed by long-range, Acr-(3)An-Acr-An
      -> Acr-An-Acr-(3)An, energy migration. With methyl viologen dication (MV(2+))
      added as a trap, Acr-(3)An + MV(2+) -> Acr-An(+) + MV(+) electron transfer
      results in sensitized electron transfer quenching over a distance of
      approximately 90 A.

PMID- 22949699
TI  - Synthesis, cellular evaluation, and mechanism of action of piperlongumine
      analogs.
AB  - Piperlongumine is a naturally occurring small molecule recently identified to be
      toxic selectively to cancer cells in vitro and in vivo. This compound was found
      to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer
      cell lines. The synthesis of 80 piperlongumine analogs has revealed structural
      modifications that retain, enhance, and ablate key piperlongumine-associated
      effects on cells, including elevation of ROS, cancer cell death, and selectivity
      for cancer cells over nontransformed cell types. Structure/activity relationships
      suggest that the electrophilicity of the C2-C3 olefin is critical for the
      observed effects on cells. Furthermore, we show that analogs lacking a reactive
      C7-C8 olefin can elevate ROS to levels observed with piperlongumine but show
      markedly reduced cell death, suggesting that ROS-independent mechanisms,
      including cellular cross-linking events, may also contribute to piperlongumine's
      induction of apoptosis. In particular, we have identified irreversible protein
      glutathionylation as a process associated with cellular toxicity. We propose a
      mechanism of action for piperlongumine that may be relevant to other small
      molecules having two sites of reactivity, one with greater and the other with
      lesser electrophilicity.

PMID- 22949700
TI  - Phenotype-based high-content chemical library screening identifies statins as
      inhibitors of in vivo lymphangiogenesis.
AB  - Lymphangiogenesis plays an important role in promoting cancer metastasis to
      sentinel lymph nodes and beyond and also promotes organ transplant rejection. We
      used human lymphatic endothelial cells to establish a reliable three-dimensional
      lymphangiogenic sprouting assay with automated image acquisition and analysis for
      inhibitor screening. This high-content phenotype-based assay quantifies sprouts
      by automated fluorescence microscopy and newly developed analysis software. We
      identified signaling pathways involved in lymphangiogenic sprouting by screening
      the Library of Pharmacologically Active Compounds (LOPAC)(1280) collection of
      pharmacologically relevant compounds. Hit characterization revealed that mitogen
      activated protein kinase kinase (MEK) 1/2 inhibitors substantially block
      lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins,
      for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in
      vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was
      mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase and subsequently the isoprenylation of Rac1. Supplementation with the
      enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic
      sprouting and the recruitment of Rac1 to the plasma membrane.

PMID- 22949701
TI  - Singular orientations and faceted motion of dislocations in body-centered cubic
      crystals.
AB  - Dislocation mobility is a fundamental material property that controls strength
      and ductility of crystals. An important measure of dislocation mobility is its
      Peierls stress, i.e., the minimal stress required to move a dislocation at zero
      temperature. Here we report that, in the body-centered cubic metal tantalum, the
      Peierls stress as a function of dislocation orientation exhibits fine structure
      with several singular orientations of high Peierls stress-stress spikes
      surrounded by vicinal plateau regions. While the classical Peierls-Nabarro model
      captures the high Peierls stress of singular orientations, an extension that
      allows dislocations to bend is necessary to account for the plateau regions. Our
      results clarify the notion of dislocation kinks as meaningful only for
      orientations within the plateau regions vicinal to the Peierls stress spikes.
      These observations lead us to propose a Read-Shockley type classification of
      dislocation orientations into three distinct classes-special, vicinal, and
      general-with respect to their Peierls stress and motion mechanisms. We predict
      that dislocation loops expanding under stress at sufficiently low temperatures,
      should develop well defined facets corresponding to two special orientations of
      highest Peierls stress, the screw and the M111 orientations, both moving by kink
      mechanism. We propose that both the screw and the M111 dislocations are jointly
      responsible for the yield behavior of BCC metals at low temperatures.

PMID- 22949702
TI  - Equilibrium at the edge and atomistic mechanisms of graphene growth.
AB  - The morphology of graphene is crucial for its applications, yet an adequate
      theory of its growth is lacking: It is either simplified to a phenomenological
      continuum level or is overly detailed in atomistic simulations, which are often
      intractable. Here we put forward a comprehensive picture dubbed nanoreactor,
      which draws from ideas of step-flow crystal growth augmented by detailed first
      principles calculations. As the carbon atoms migrate from the feedstock to
      catalyst to final graphene lattice, they go through a sequence of states whose
      energy levels can be computed and arranged into a step-by-step map. Analysis
      begins with the structure and energies of arbitrary edges to yield equilibrium
      island shapes. Then, it elucidates how the atoms dock at the edges and how they
      avoid forming defects. The sequence of atomic row assembly determines the kinetic
      anisotropy of growth, and consequently, graphene island morphology, explaining a
      number of experimental facts and suggesting how the growth product can further be
      improved. Finally, this analysis adds a useful perspective on the synthesis of
      carbon nanotubes and its essential distinction from graphene.

PMID- 22949703
TI  - Geometry sensing by self-organized protein patterns.
AB  - In the living cell, proteins are able to organize space much larger than their
      dimensions. In return, changes of intracellular space can influence biochemical
      reactions, allowing cells to sense their size and shape. Despite the possibility
      to reconstitute protein self-organization with only a few purified components, we
      still lack knowledge of how geometrical boundaries affect spatiotemporal protein
      patterns. Following a minimal systems approach, we used purified proteins and
      photolithographically patterned membranes to study the influence of spatial
      confinement on the self-organization of the Min system, a spatial regulator of
      bacterial cytokinesis, in vitro. We found that the emerging protein pattern
      responds even to the lateral, two-dimensional geometry of the membrane such that,
      as in the three-dimensional cell, Min protein waves travel along the longest axis
      of the membrane patch. This shows that for spatial sensing the Min system does
      not need to be enclosed in a three-dimensional compartment. Using a computational
      model we quantitatively analyzed our experimental findings and identified
      persistent binding of MinE to the membrane as requirement for the Min system to
      sense geometry. Our results give insight into the interplay between geometrical
      confinement and biochemical patterns emerging from a nonlinear reaction-diffusion
      system.

PMID- 22949704
TI  - Molecular mechanisms of cobalt-catalyzed hydrogen evolution.
AB  - Several cobalt complexes catalyze the evolution of hydrogen from acidic
      solutions, both homogeneously and at electrodes. The detailed molecular
      mechanisms of these transformations remain unresolved, largely owing to the fact
      that key reactive intermediates have eluded detection. One method of stabilizing
      reactive intermediates involves minimizing the overall reaction free-energy
      change. Here, we report a new cobalt(I) complex that reacts with tosylic acid to
      evolve hydrogen with a driving force of just 30 meV/Co. Protonation of Co(I)
      produces a transient Co(III)-H complex that was characterized by nuclear magnetic
      resonance spectroscopy. The Co(III)-H intermediate decays by second-order
      kinetics with an inverse dependence on acid concentration. Analysis of the
      kinetics suggests that Co(III)-H produces hydrogen by two competing pathways: a
      slower homolytic route involving two Co(III)-H species and a dominant heterolytic
      channel in which a highly reactive Co(II)-H transient is generated by Co(I)
      reduction of Co(III)-H.

PMID- 22949705
TI  - Tension induces a base-paired overstretched DNA conformation.
AB  - Mixed-sequence DNA molecules undergo mechanical overstretching by approximately
      70% at 60-70 pN. Since its initial discovery 15 y ago, a debate has arisen as to
      whether the molecule adopts a new form [Cluzel P, et al. (1996) Science 271:792
      794; Smith SB, Cui Y, Bustamante C (1996) Science 271:795-799], or simply
      denatures under tension [van Mameren J, et al. (2009) Proc Natl Acad Sci USA
      106:18231-18236]. Here, we resolve this controversy by using optical tweezers to
      extend small 60-64 bp single DNA duplex molecules whose base content can be
      designed at will. We show that when AT content is high (70%), a force-induced
      denaturation of the DNA helix ensues at 62 pN that is accompanied by an extension
      of the molecule of approximately 70%. By contrast, GC-rich sequences (60% GC) are
      found to undergo a reversible overstretching transition into a distinct form that
      is characterized by a 51% extension and that remains base-paired. For the first
      time, results proving the existence of a stretched basepaired form of DNA can be
      presented. The extension observed in the reversible transition coincides with
      that produced on DNA by binding of bacterial RecA and human Rad51, pointing to
      its possible relevance in homologous recombination.

PMID- 22949706
TI  - Cytoplasmic streaming in Drosophila oocytes varies with kinesin activity and
      correlates with the microtubule cytoskeleton architecture.
AB  - Cells can localize molecules asymmetrically through the combined action of
      cytoplasmic streaming, which circulates their fluid contents, and specific
      anchoring mechanisms. Streaming also contributes to the distribution of nutrients
      and organelles such as chloroplasts in plants, the asymmetric position of the
      meiotic spindle in mammalian embryos, and the developmental potential of the
      zygote, yet little is known quantitatively about the relationship between
      streaming and the motor activity which drives it. Here we use Particle Image
      Velocimetry to quantify the statistical properties of Kinesin-dependent streaming
      during mid-oogenesis in Drosophila. We find that streaming can be used to detect
      subtle changes in Kinesin activity and that the flows reflect the architecture of
      the microtubule cytoskeleton. Furthermore, based on characterization of the
      rheology of the cytoplasm in vivo, we establish estimates of the number of
      Kinesins required to drive the observed streaming. Using this in vivo data as the
      basis of a model for transport, we suggest that the disordered character of
      transport at mid-oogenesis, as revealed by streaming, is an important component
      of the localization dynamics of the body plan determinant oskar mRNA.

PMID- 22949707
TI  - De novo automated design of small RNA circuits for engineering synthetic
      riboregulation in living cells.
AB  - A grand challenge in synthetic biology is to use our current knowledge of RNA
      science to perform the automatic engineering of completely synthetic sequences
      encoding functional RNAs in living cells. We report here a fully automated design
      methodology and experimental validation of synthetic RNA interaction circuits
      working in a cellular environment. The computational algorithm, based on a
      physicochemical model, produces novel RNA sequences by exploring the space of
      possible sequences compatible with predefined structures. We tested our
      methodology in Escherichia coli by designing several positive riboregulators with
      diverse structures and interaction models, suggesting that only the energy of
      formation and the activation energy (free energy barrier to overcome for
      initiating the hybridization reaction) are sufficient criteria to engineer RNA
      interaction and regulation in bacteria. The designed sequences exhibit
      nonsignificant similarity to any known noncoding RNA sequence. Our riboregulatory
      devices work independently and in combination with transcription regulation to
      create complex logic circuits. Our results demonstrate that a computational
      methodology based on first-principles can be used to engineer interacting RNAs
      with allosteric behavior in living cells.

PMID- 22949708
TI  - Genetic systems for functional cell ablation in Drosophila.
AB  - The selective removal of cells by ablation is a powerful tool in the study of
      eukaryotic developmental biology, providing much information about the origin,
      fate, or function of these cells in the developing organism. In Drosophila, three
      main methods have been used to ablate cells: chemical, genetic, and laser
      ablation. Each method has its own applicability with regard to developmental
      stage and the cells to be ablated, and its own limitations. This article
      describes genetic systems for functional cell ablation in Drosophila. Genetic
      ablation consists of delivering a toxin or death-inducing gene under the control
      of a cell-specific enhancer, or by means of the GAL4 system. Because of the wide
      range of existing enhancers, toxins and death genes can be targeted to virtually
      any cell of choice, allowing for cell-type-specificity. Genetic ablation is less
      expensive and less labor-intensive than laser ablation. It allows one to analyze
      the effects of eliminating every cell of a given type within an embryo, and also
      allows the examination of populations rather than individuals.

PMID- 22949709
TI  - TUNEL-antibody double-labeling method for Drosophila embryos.
AB  - The terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling
      (TUNEL) method for monitoring targeted cell ablation is based on the in situ
      labeling of DNA fragmentation sites in nuclei of intact fixed cells. Unlike other
      methods of detecting dying cells, the use of fixed material allows antigen
      expression to be monitored at the same time that apoptosis is confirmed in the
      targeted cells. Double-labeling of Drosophila embryos using the TUNEL reaction
      and fluorescently tagged antibodies can be adapted to the selected antigen. For
      some antigens, it is preferable that the TUNEL reaction be performed first,
      whereas for others, the TUNEL reaction should follow antigen detection. This may
      be because some antigens may not survive the 37 degrees C incubation or the
      conditions of the reaction. Similarly, increased fixation times yield better
      results for some antigens, but not for others. This protocol describes a TUNEL
      reaction adapted for use on Drosophila embryos in conjunction with fluorescently
      labeled antibodies.

PMID- 22949710
TI  - Intracardial embryonic delivery of developmental modifiers in utero.
AB  - Our knowledge of organ ontogeny is largely based on loss-of-function (knockout)
      or gain-of-function (transgenesis) approaches. However, developmental modulators
      such as proteins, mRNAs, microRNAs(miRNAs), small interfering RNAs, and other
      small molecules may complement the above DNA-modifying technologies in a much
      more direct way. Unfortunately, their use is often limited by the ability of
      these compounds to cross the placenta and reach physiologically relevant
      concentrations when administered systemically to the mother. The design of safe
      and effective techniques to deliver these compounds into the embryo is therefore
      an area of great scientific potential. In this article we report a new method for
      introducing developmental modulators into murine embryos by means of direct
      injection into the heart. Unlike other reported methods that require surgical
      exposure of the uterus, our percutaneous ultrasound-guided approach allows for
      the intracardial injection of mouse embryos as early as embryonic day 10.5
      (e10.5) and throughout gestation in a minimally invasive manner that largely
      preserves embryo viability. This system offers a critical advantage over in vitro
      settings because the effects of any given treatment can be observed without
      disturbing the native environment of the developing organ. Procedures are
      described for the delivery and detection of transducible proteins as well as
      morpholinos designed to block the expression of specific miRNAs within the living
      embryo.

PMID- 22949711
TI  - Labeling and confocal imaging of neurons in thick invertebrate tissue samples.
AB  - Neuroscience researchers have long sought methods to describe the neural
      connectivity of the circuits responsible for specific behaviors. One major
      obstacle is scale: Neural spines can be <1 um in diameter, but axons can range
      from millimeters to centimeters (or larger) in length, making tissue imaging and
      neuron reconstruction a challenging task. New tissue-clearing agents and long
      working-distance objectives offer improved imaging conditions, and here we
      present a complete protocol for invertebrate tissue that uses these advances. In
      this protocol, tissue-processing steps previously published in separate articles
      are combined with recent advances in confocal imaging to visualize invertebrate
      tissue samples that are >500 um thick and contain dye-filled neurons. The steps
      describe dye filling, fixing, antibody labeling, clearing, whole tissue mounting,
      and confocal imaging with matched refractive indexes. Thus, manual sectioning or
      "flipping" the tissue to image the whole volume is not required. With matched
      refractive indexes, loss of resolution and signal is avoided. Tissue volumes are
      imaged in one stack and nonlinear deformations caused by tissue flipping are
      prevented. We apply the protocol to whole dragonfly thoracic ganglia (2 * 1 * 0.6
      mm) and cephalopod skin samples (20 * 2 * 0.6 mm) with minimal tissue
      deformation. The resulting images will be used to develop a three-dimensional
      connectivity atlas of dragonfly ganglia and cephalopod skin innervation. This
      protocol can be applied to other invertebrate species, and has the advantage that
      it avoids problems with antigen specificity.

PMID- 22949712
TI  - Imaging axon pathfinding in Xenopus in vivo.
AB  - Axon pathfinding in the developing animal involves a highly dynamic process in
      which the axonal growth cone makes continuous decisions as it navigates toward
      its target. Changes occurring in the growth cone with respect to retracting from
      or extending into complex new territories can occur in minutes. Thus, the advent
      of strategies to visualize axon path-finding in vivo in a live intact animal is
      crucial for a better understanding of how the growth cone makes such rapid
      decisions in response to multiple cues. Combining these strategies with loss-of
      function and/or gain-of-function techniques allows one to gain some insight as to
      which molecules are crucial to particular growth cone behaviors at specific
      choice points during navigation. The main advantage of using Xenopus lies in the
      accessibility of major axon tracts for live microscopy, as their embryonic
      development occurs ex utero. Furthermore, the robust embryos remain healthy
      during immobilization and allow for good imaging for long periods. This protocol
      describes the methods for stabilizing and preparing live Xenopus embryos for
      imaging labeled axonal tracts at high spatial and temporal resolution for up to
      72 h. This approach can been used to investigate how the knockdown of certain
      gene functions can affect the speed of navigation through the well-studied
      Xenopus retinotectal pathway. It can be adapted to visualize other axon tracts of
      interest.

PMID- 22949713
TI  - Imaging axon pathfinding in zebrafish in vivo.
AB  - Axon pathfinding in the developing animal involves a highly dynamic process in
      which the axonal growth cone makes continuous decisions as it navigates toward
      its target. Changes occurring in the growth cone with respect to retracting from
      or extending into complex new territories can occur in minutes. Thus, the advent
      of strategies to visualize axon path-finding in vivo in a live intact animal is
      crucial for a better understanding of how the growth cone makes such rapid
      decisions in response to multiple cues. Combining these strategies with loss-of
      function and/or gain-of-function techniques, one can gain some insight as to
      which molecules are crucial to particular growth cone behaviors at specific
      choice points during navigation. The major advantage of using zebrafish lies in
      the accessibility of major axon tracts for live microscopy, as their embryonic
      development occurs ex utero. Furthermore, the robust embryos remain healthy
      during immobilization and allow for good imaging for long periods. This protocol
      describes the method for stabilizing and preparing live zebrafish embryos for
      imaging labeled axonal tracts at high spatial and temporal resolution for up to
      72 h. It has been used for retinotectal axon pathfinding, but can be adapted to
      visualize other axon tracts of interest.

PMID- 22949714
TI  - Corneal pocket assay in rabbits.
AB  - The anterior chamber of the eye is a natural site for observing tumor growth, and
      implantation in a corneal pocket can be used for this purpose. This protocol
      describes the corneal pocket assay in rabbits. Because of the 3D nature of vessel
      growth, it is difficult to quantify the vascular response except in the early
      stages when the vessel length/number can be assessed. The assay can be used for
      mice with modification. Although it is less expensive to use rats/mice compared
      with rabbits, surgery on smaller eyes is more difficult. Furthermore, because the
      rat/mouse cornea is thinner than the rabbit's, the three-dimensional (3D) growth
      of vessels is even more limited.

PMID- 22949715
TI  - Circuit mapping by ultraviolet uncaging of glutamate.
AB  - In laser photostimulation, small clusters of neurons in brain slices are induced
      to fire action potentials by focal glutamate uncaging, and synaptic connectivity
      between photoexcited presynaptic neurons and individual postsynaptic neurons is
      assessed by intracellular recording of synaptic events. With a scanner, this
      process can be repeated sequentially across a patterned array of stimulus
      locations, generating maps of neurons' local sources of synaptic inputs. Laser
      scanning photostimulation (LSPS) based on patterned glutamate uncaging offers an
      efficient, quantitative, optical-electrophysiological way to map synaptic
      circuits in brain slices. The efficacy of glutamate-based photostimulation for
      circuit mapping (in contrast to electrical stimulation) derives from the ability
      to stimulate neurons with high precision and speed, and without stimulating axons
      of passage. This protocol describes the components, assembly, and operation of a
      laser scanning microscope for ultraviolet (UV) uncaging, along with experimental
      methods for circuit mapping in brain slices. It presents a general approach and a
      set of guidelines for quantitative circuit mapping using "standard" LSPS methods
      based on single-photon glutamate uncaging using a UV laser, a pair of scanning
      mirror galvanometers, a patch-clamp setup, and open-source data acquisition
      software.

PMID- 22949716
TI  - Arc lamps and monochromators for fluorescence microscopy.
AB  - Fluorescence microscopy requires high photon-flux densities in the specimen
      plane. These intensities are only achieved by lasers, arc lamps, and, most
      recently, light-emitting diodes (LEDs). Lasers and LEDs, however, are restricted
      to a limited number of wavelength regions, whereas with arc lamps it is possible
      to select arbitrary wavelengths and wavelength regions. Moreover, the lower cost
      of arc lamps, compared with lasers, makes them the light source of choice for the
      majority of fluorescence microscopy applications. Recently, so-called white light
      lasers have become commercially available, but their photon fluxes--although
      sufficient for laser scanning applications--are still not high enough for
      applications where extended areas need to be illuminated. This article discusses
      arc lamps and the design and performance of an arc lamp-based illumination system
      for fluorescence microscopy that allows the user to choose any wavelength from
      ultraviolet (UV) to infrared. The system permits rapid switching speed between
      colors, while maintaining quite stable and homogenous emissions.

PMID- 22949717
TI  - Labeling DNA (or RNA) for single-molecule FRET.
AB  - Single-molecule (sm) fluorescence detection is a powerful method for studying
      biological events without time and population averaging. Forster (fluorescence)
      resonance energy transfer (FRET) is a spectroscopic technique for measuring
      distances in the 30-80 A range in which excitation energy of a donor molecule is
      transferred to an acceptor via interaction between two induced dipoles. A variant
      of smFRET is based on total internal reflection (TIR) microscopy. This protocol
      describes the labeling of nucleic acids (DNA or RNA) for smFRET with TIR
      microscopy. The protocol is optimized for 5 nanomoles of DNA that has an amine
      modified thymine in its sequence. It is a simplified version of a protocol from
      Invitrogen.

PMID- 22949718
TI  - Labeling proteins for single-molecule FRET.
AB  - Single-molecule (sm) fluorescence detection is a powerful method for studying
      biological events without time and population averaging. Forster (fluorescence)
      resonance energy transfer (FRET) is a spectroscopic technique for measuring
      distances in the 30-80 A range in which excitation energy of a donor molecule is
      transferred to an acceptor via interaction between two induced dipoles. A variant
      of smFRET is based on total internal reflection (TIR) microscopy. This protocol
      describes the labeling of protein for smFRET with TIR microscopy. It is based on
      a labeling procedure for E. coli Rep helicase. A different assay (e.g., different
      chemical conditions) may be required for other proteins.

PMID- 22949719
TI  - SV40 in vitro packaging: a pseudovirion gene delivery system.
AB  - Nuclear extracts of Spodoptera frugiperda (Sf9) insect cells infected with
      baculoviruses encode the simian virus 40 (SV40) major coat protein (VP1). As
      described in this protocol, these extracts are able to package supercoiled
      plasmid DNA or RNA interference (RNAi) sequences in the presence of MgCl(2),
      CaCl(2), and ATP, thus forming SV40 pseudovirions in vitro. Such packaging has
      numerous advantages over other viral and nonviral delivery systems. Specifically,
      it provides a wide host range and high transduction efficiency. The only major
      disadvantage of this system is low expression per transduced cell observed in
      vitro, likely a result of DNA trapped in the cytoplasmic compartment of the cell
      that does not enter the cell nucleus.

PMID- 22949720
TI  - The precision of estimates in stereological analyses.
AB  - When quantifying the total volume, number, length, or surface of morphological
      features in complex structures such as the brain, it is neither desirable nor
      feasible to make absolute determinations of these parameters. It would take a
      lifetime to count all of the neurons or measure the total length of dendrites in
      many parts of the brain. Estimates based on a relatively small number of samples
      of even the most complex structures will suffice, if the estimates are unbiased
      and have a sufficient amount of precision. It is important to have an
      understanding of what the precision of an estimate actually means and how it can
      be calculated and altered, to optimize studies with regard to the number of
      individuals, sections, and probes used in an analysis. An optimal sampling scheme
      is one that involves a minimum of sampling but still provides enough precision to
      draw a conclusion with a predetermined level of confidence.

PMID- 22949721
TI  - Bacterial RNA isolation.
AB  - In this bacterial RNA isolation protocol, an "RNA-protective" treatment is
      followed by lysozyme digestion of the peptidoglycan component of the cell wall.
      EDTA promotes the loss of the outer membrane of Gram-negative bacteria and allows
      the lysozyme better access to the peptidoglycan. Cells begin to lyse during
      digestion in hypotonic lysozyme buffer and lysis is completed by sodium dodecyl
      sulfate (SDS) and hot phenol:chloroform:isoamyl alcohol (PCA) extraction. SDS and
      hot phenol disrupt membranes, denature protein (including RNase), and strip
      proteins from RNA. The separation of the organic phase from the aqueous phase is
      achieved using Phase Lock Gel, an inert material with a density intermediate
      between the organic and aqueous samples. The sample is split into three phases:
      from bottom to top, these are phenol and chloroform (organic phase), the inert
      gel with the interface material, and the aqueous phase with the RNA. The gel acts
      as a physical barrier between the sample and the organic phase plus interface.
      Following organic extraction, the RNA is concentrated by ethanol precipitation.

PMID- 22949722
TI  - RNAi in cultured mammalian cells using synthetic siRNAs.
AB  - RNA interference (RNAi) enables sequence-specific, experimentally induced
      silencing of almost any gene by tapping into innate regulatory mechanisms that
      are conserved among virtually all eukaryotes. In a typical RNAi experiment, an
      artificial silencing trigger directs the RNAi pathway toward a target that it
      would not normally recognize. This is most often an endogenous protein-coding
      gene, although some noncoding RNAs can also be silenced effectively. The
      artificial silencing trigger varies; this protocol uses synthetic small
      interfering RNAs (siRNAs). Lipofectamine 2000 is used to deliver the siRNAs into
      HEK293 cells. This lipid reagent has proven to be effective for many different
      cultured mammalian cell lines.

PMID- 22949724
TI  - Robert Ader: psychologist, past president of the American Psychosomatic Society,
      and pioneer in psychoneuroimmunology research.

PMID- 22949725
TI  - Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption
      and cumulus cell expansion in the pig.
AB  - To define signaling pathways that drive FSH- and epidermal growth factor (EGF)
      like peptide-induced cumulus expansion and oocyte meiotic resumption, in vitro
      cultured pig cumulus-oocyte complexes were treated with specific protein kinase
      inhibitors. We found that FSH-induced maturation of oocytes was blocked in
      germinal vesicle (GV) stage by protein kinase A (PKA), MAPK14, MAPK3/1, and EGF
      receptor (EGFR) tyrosine kinase inhibitors (H89, SB203580, U0126, and AG1478
      respectively) whereas phosphoinositide-3-kinase/v-akt murine thymoma viral
      oncogene homolog (PI3K/AKT) inhibitor (LY294002) blocked maturation of oocytes in
      metaphase I (MI). Amphiregulin (AREG)-induced maturation of oocytes was
      efficiently blocked in GV by U0126, AG1478, and low concentrations of LY294002;
      H89, SB203580, and high concentrations of LY294002 allowed the oocytes to undergo
      breakdown of GV and blocked maturation in MI. Both FSH- and AREG-induced cumulus
      expansion was incompletely inhibited by H89 and completely inhibited by SB203580,
      U0126, AG1478, and LY294002. The inhibitors partially or completely inhibited
      expression of expansion-related genes (HAS2, PTGS2, and TNFAIP6) with two
      exceptions: H89 inhibited only TNFAIP6 expression and LY294002 increased
      expression of PTGS2. The results of this study are consistent with the idea that
      PKA and MAPK14 pathways are essential for FSH-induced transactivation of the
      EGFR, and synthesis of EGF-like peptides in cumulus cells and MAPK3/1 is involved
      in regulation of transcriptional and posttranscriptional events in cumulus cells
      required for meiotic resumption and cumulus expansion. PI3K/AKT signaling is
      important for regulation of cumulus expansion, AREG-induced meiotic resumption,
      and oocyte MI/MII transition. The present data also indicate the existence of an
      FSH-activated and PKA-independent pathway involved in regulation of HAS2 and
      PTGS2 expression in cumulus cells.

PMID- 22949726
TI  - Early consultation with a rheumatologist for RA: does it reduce subsequent use of
      orthopaedic surgery?
AB  - OBJECTIVE: Optimal care in RA includes early use of DMARDs to prevent joint
      damage and hopefully decrease the need for costly surgical interventions. Our
      objective was to determine whether a reduced rate of orthopaedic surgery was
      evident for persons with RA who saw a rheumatologist early in the disease course.
      METHODS: We studied persons who had a diagnosis of RA based on billing code data
      in the province of Quebec in 1995, and for whom the initial date of RA diagnosis
      by a non-rheumatologist could be established before the confirmatory diagnosis by
      the rheumatologist. We followed these patients until 2007. Patients were
      classified as early consulters or late consulters depending on whether they were
      seen by a rheumatologist within or beyond 3 months of being diagnosed with RA by
      their referring physician. The outcome, orthopaedic surgery, was defined using
      International Classification of Diseases (ICD) procedure codes ICD9 and ICD10.
      Multivariate Cox regression with time-dependent covariates estimated the effect
      of early consultation on the time to orthopaedic surgery. RESULTS: Our cohort
      consisted of 1051 persons; mean age at diagnosis was 55.7 years, 68.2% were
      female and 50.7% were early consulters. Among all patients, 20.5% (215) had an
      orthopaedic surgery during the observation interval. Early consulters were less
      likely to undergo orthopaedic surgery during the 12-year follow-up period
      (adjusted hazard ratio 0.60, 95% CI 0.44, 0.82). CONCLUSION: Persons with RA who
      consult a rheumatologist later in the disease course have a worse outcome in
      terms of eventual requirement for orthopaedic surgery.

PMID- 22949727
TI  - Gout and its comorbidities: implications for therapy.
AB  - Gout is a common form of arthritis. It is associated with a number of
      comorbidities, including hypertension, cardiovascular disease, renal impairment,
      diabetes, obesity, hyperlipidaemia and frequently in a combination known as the
      metabolic syndrome. These comorbidities and their treatment may have an effect on
      the development of gout and on the choice of therapeutic agent. Treatment of
      acute gout with short-term corticosteroids may be a safer option than either
      NSAIDs or colchicine in patients with significant renal and/or cardiac
      impairment. Sustained reduction of serum urate <0.36 mmol/l is required for long
      term management of gout. The optimal dosing regimen for patients with renal
      impairment is the subject of on-going investigation. There is less experience
      with newer urate-lowering therapies. This review will consider the relationship
      between comorbidities and gout with a particular focus on the treatment of gout
      and the potential interactions between drugs used for gout and those for comorbid
      conditions.

PMID- 22949728
TI  - Comment on: non-infectious pulmonary toxicity of rituximab: a systematic review.

PMID- 22949729
TI  - Detection of free light chain monoclonal proteins co-migrating with intact
      monoclonal proteins in patients with monoclonal gammopathy.
AB  - BACKGROUND: In a small, but potentially significant proportion of patients with a
      monoclonal gammopathy, patients show the existence of an intact monoclonal (M-)
      protein co-migrating with a free light chain (FLC) M-protein. Using traditional
      methods for detection of monoclonal immunoglobulins, only the intact M-protein
      may be detectable, and hence the FLC M-proteins may be missed. METHODS:
      Immunofixation electrophoresis (IFE) using two different sets of antisera were
      compared (one detecting both free and bound FLC epitopes, and one detecting only
      the free FLC epitopes), alongside urine protein electrophoresis and the Freelite
      assay in order to ascertain the best methods of detecting both types of M
      proteins in this subset of patients. RESULTS: A total of 2% of the patient
      population tested were shown to have a FLC M-protein migrating coincidentally
      with an intact M-protein. These were not detected by IFE using the widely
      utilised antisera to both free and bound FLC epitopes, and hence may have been
      missed during routine testing, but were detectable using the other methods.
      CONCLUSIONS: This study highlights the important finding that in some patients
      with both an intact and a FLC M-protein, the FLC M-protein may be missed during
      routine testing. In incidences where no corresponding urine sample is sent to the
      laboratory alongside the serum sample, we would suggest testing for the presence
      of FLC M-proteins in this subset of patients using the Freelite assay, if no
      urine sample can be obtained, to ensure all FLC M-proteins are appropriately
      detected.

PMID- 22949730
TI  - A future for faecal haemoglobin measurements in the medical laboratory.
AB  - Guaiac-based faecal occult blood tests (gFOBT) are still used in asymptomatic
      population bowel screening programmes but are being replaced by faecal
      immunochemical tests (FIT) for haemoglobin. gFOBT have many well-documented
      disadvantages and there is little evidence for their use in assessment of the
      symptomatic. Many laboratories have eliminated gFOBT from their approved
      repertoires by invoking the authoritative published guidelines. Data continue to
      accumulate that gFOBT are obsolete. FIT are available in two formats, qualitative
      and quantitative, the latter having advantages that the faecal haemoglobin
      concentrations are measured and cut-off concentrations that stimulate further
      investigation can be user-defined. There is growing evidence that FIT would be
      useful in a spectrum of clinical settings in addition to screening. All
      laboratories should have FIT in their existing repertoire. For some uses,
      qualitative FIT would be adequate. However, much evidence has accumulated that
      measurements of faecal haemoglobin concentrations are beneficial for the
      assessment of both disease severity and the future risk of colorectal neoplasia.
      Interpretation requires appreciation that faecal haemoglobin concentrations are
      higher in men than women and rise with age. It might well be that risk scoring
      systems that take gender and age into account, possibly with other factors
      including symptoms, will benefit individuals. Laboratories should consider how
      quantitative faecal haemoglobin measurements could be brought into routine
      practice and included in their forward planning. External quality assessment is
      needed. Specialists in laboratory medicine are urged to play a significant role
      in the research and development still required to make this a truly mature
      investigation.

PMID- 22949731
TI  - Testosterone measurement by liquid chromatography tandem mass spectrometry: the
      importance of internal standard choice.
AB  - BACKGROUND: Testosterone measurement by liquid chromatography tandem mass
      spectrometry (LC-MS/MS) is well accepted as the preferred technique for the
      analysis of testosterone. Variation is seen between assays and is likely to be
      due to method differences. One area of inconsistency among assays is the choice
      of internal standard. We investigated the effects of three internal standards.
      METHODS: Testosterone with two deuterium (D2), five deuterium (D5) and three
      carbon 13 enrichment (C13) were separately assessed. Samples were extracted using
      ether following the addition of 10 MUL of internal standard. All aliquots were
      prepared in triplicate, one for each type of internal standard. After mixing, the
      ether was transferred to a 96-deep well block, and then evaporated to dryness.
      Extracts were reconstituted with 50% mobile phases and analysed using a Waters
      Acquity UPLC and Quattro Premier tandem mass spectrometer. This method had
      previously been shown to have excellent agreement with a reference method using
      the D2 internal standard and this was considered the target. RESULTS: Lower
      results were obtained when using D5 testosterone when compared with D2
      testosterone. The C13 internal standard also gave lower results, but was closer
      to the D2 target than the D5 internal standard. CONCLUSIONS: The choice of
      internal standard alone can have a significant affect on the results obtained by
      LC-MS/MS assays for testosterone using this chromatography. The effects of the
      combination of chromatography and internal standard choice should be investigated
      during method development.

PMID- 22949732
TI  - Breast compression in mammography: pressure distribution patterns.
AB  - BACKGROUND: Breast compression is important in mammography in order to improve
      image quality, better separate tissue components, and reduce absorbed dose to the
      breast. In this study we use a method to measure and visualize the distribution
      of pressure over a compressed breast in mammography. PURPOSE: To measure and
      describe the pressure distribution over the breast as a result of applied breast
      compression in mammography. MATERIAL AND METHODS: One hundred and three women
      aged 40.7-74.3 years (median, 48.9 years) invited for mammographic screening
      consented to take part in this study. They were subjected to two additional
      breast compressions of the left breast (standard force and approximately 50%
      reduction). Pressure images of the compressed breast were obtained using force
      sensing resistor (FSR) sensors placed underneath the compression plate. Subjects
      rated their experience of pain on a visual analogue scale (VAS). RESULTS: Four
      pressure patterns were identified, fitting 81 of the 103 breasts, which were
      grouped accordingly. The remaining 22 breasts were found to correspond to a
      combination of any two patterns. Two groups (43 breasts) showed pressure mainly
      over the juxtathoracic part of the breast, had significantly greater breast
      thickness (P = 0.003) and had a lower mean pressure over dense tissue (P <
      0.0001) than those with more evenly distributed pressure. Reducing compression
      force increased average breast thickness by 1.8 mm (P < 0.0001). CONCLUSION: The
      distribution of pressure differed greatly between breasts. In a large proportion
      of breasts the compression plate did not provide optimal compression of the
      breast, the compression force being absorbed in juxtathoracic structures.

PMID- 22949733
TI  - Deficits in domains of social cognition in schizophrenia: a meta-analysis of the
      empirical evidence.
AB  - OBJECTIVE: Social cognition is strongly associated with functional outcome in
      schizophrenia, making it an important target for treatment. Our goal was to
      examine the average magnitude of differences between schizophrenia patients (SCs)
      and normal comparison (NCs) patients across multiple domains of social cognition
      recognized by the recent NIMH consensus statement: theory of mind (ToM), social
      perception, social knowledge, attributional bias, emotion perception, and emotion
      processing. METHOD: We conducted a meta-analysis of peer-reviewed studies of
      social cognition in schizophrenia, published between 1980 and November, 2011.
      RESULTS: 112 studies reporting results from 3908 SCs and 3570 NCs met our
      inclusion criteria. SCs performed worse than NCs across all domains, with large
      effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g =
      0.89), and emotion processing (g = 0.88). Regression analyses showed that
      statistically significant heterogeneity in effects within domains was not
      explained by age, education, or gender. Greater deficits in social and emotion
      perception were associated with inpatient status, and greater deficits in emotion
      processing were associated with longer illness duration. CONCLUSIONS: Despite the
      limitations of existing studies, including lack of standardization or
      psychometric validation of measures, the evidence for deficits across multiple
      social cognitive domains in schizophrenia is clear. Future research should
      examine the role of neurobiological and psychosocial factors in models linking
      various aspects of deficit in schizophrenia, including social cognition, in order
      to identify targets for intervention.

PMID- 22949734
TI  - Allosteric regulation of nucleotidyl cyclases: an emerging pharmacological
      target.
AB  - Adenylyl cyclases (ACs) and guanylyl cyclases (GCs) produce the second messengers
      cyclic adenosine monophosphate and cyclic guanosine monophosphate, respectively.
      ACs and GCs are differentially regulated by intercellular signaling molecules and
      are implicated in various disease states, including cardiovascular diseases,
      aging, pain, and neuropsychiatric ailments. Hence, ACs and GCs constitute
      interesting drug targets. Because the catalytic sites of these enzymes are highly
      conserved, it is difficult to achieve isoform specificity. However, studies have
      provided evidence for the notion that regulatory allosteric domains in the
      vicinity of the catalytic site provide new opportunities for pharmacological
      intervention. Here, we summarize the current status of such research and discuss
      future directions in this exciting field.

PMID- 22949735
TI  - FAM123A binds to microtubules and inhibits the guanine nucleotide exchange factor
      ARHGEF2 to decrease actomyosin contractility.
AB  - The FAM123 gene family comprises three members: FAM123A, the tumor suppressor WTX
      (also known as FAM123B), and FAM123C. WTX is required for normal development and
      causally contributes to human disease, in part through its regulation of beta
      catenin-dependent WNT signaling. The roles of FAM123A and FAM123C in signaling,
      cell behavior, and human disease remain less understood. We defined and compared
      the protein-protein interaction networks for each member of the FAM123 family by
      affinity purification and mass spectrometry. Protein localization and functional
      studies suggest that the FAM123 family members have conserved and divergent
      cellular roles. In contrast to WTX and FAM123C, we found that microtubule
      associated proteins were enriched in the FAM123A protein interaction network.
      FAM123A interacted with and tracked with the plus end of dynamic microtubules.
      Domain interaction experiments revealed a "SKIP" amino acid motif in FAM123A that
      mediated interaction with the microtubule tip tracking proteins end-binding
      protein 1 (EB1) and EB3--and therefore with microtubules. Cells depleted of
      FAM123A showed compartment-specific effects on microtubule dynamics, increased
      actomyosin contractility, larger focal adhesions, and decreased cell migration.
      These effects required binding of FAM123A to and inhibition of the guanine
      nucleotide exchange factor ARHGEF2, a microtubule-associated activator of RhoA.
      Together, these data suggest that the SKIP motif enables FAM123A, but not the
      other FAM123 family members, to bind to EB proteins, localize to microtubules,
      and coordinate microtubule dynamics and actomyosin contractility.

PMID- 22949737
TI  - Critically appraised topic: the effect of hospice care in patients with dementia.

PMID- 22949736
TI  - Guanylyl cyclases A and B are asymmetric dimers that are allosterically activated
      by ATP binding to the catalytic domain.
AB  - It is not known how natriuretic peptides and adenosine triphosphate (ATP)
      activate guanylyl cyclase A (GC-A) and GC-B, which generate the second messenger
      cyclic guanosine monophosphate. We determined that natriuretic peptides increased
      the maximum rate of these enzymes >10-fold in a positive cooperative manner in
      the absence of ATP. In the absence of natriuretic peptides, ATP shifted substrate
      velocity profiles from cooperative to linear but did not increase the affinity of
      GCs for the substrate guanosine triphosphate (GTP) since the Michaelis constant
      was unchanged. However, in the presence of natriuretic peptides, ATP competed
      with GTP for binding to an allosteric site, which enhanced the activation of GCs
      by decreasing the Michaelis constant. Thus, natriuretic peptide binding was
      required for communication of the allosteric activation signal to the catalytic
      site. The ability of ATP to activate GCs decreased and enzyme potency (a measure
      of sensitivity to stimulation) increased with increasing GTP concentrations.
      Point mutations in the purine-binding site of the catalytic domain abolished GC
      activity but not allosteric activation. Coexpression of inactive mutants produced
      half the activity expected for symmetric catalytic dimers. 2'-Deoxy-ATP and 2'
      deoxy-GTP were poor allosteric activators, but 2'-deoxy-GTP was an effective
      substrate, consistent with distinct binding requirements for the allosteric and
      catalytic sites. We conclude that membrane GC domains are asymmetric homodimers
      with distinct and reciprocally regulated catalytic and allosteric sites that bind
      to GTP and ATP, respectively. These data define a new membrane GC activation
      model and provide evidence of a previously unidentified GC drug interaction site.

PMID- 22949738
TI  - Would you go broke to stay alive in Singapore? Further analysis of a survey on
      how costs may affect choice of therapy.
AB  - AIMS: This study attempts to explore how high treatment costs can result in
      people foregoing necessary treatment. METHODS: Health care professionals (HCPs)
      were invited to complete a questionnaire survey, in which they were requested to
      imagine that they had locally recurrent head and neck cancers. They were then
      asked to choose a treatment in each of the 3 scenarios, which differed only in
      the cost of treatment. RESULTS: Majority would choose the cheapest treatment
      option if treatment costs mirrored that in real life. But majority would opt for
      the treatment that gave the greatest median survival, if cost was not an issue.
      CONCLUSION: High cost of treatment can be a strong deterrent to patients who need
      and can benefit from those treatments.

PMID- 22949739
TI  - Specialized palliative care services in Japan: a nationwide survey of resources
      and utilization by patients with cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the availability and
      utilization of specialized palliative care services among patients with cancer in
      Japan. METHODS: We conducted a nationwide cross-sectional survey of 828
      institutions predicted to provide specialized palliative care services. RESULTS:
      Responses were received from 751 institutions (response rate, 91%); of these, 541
      had specialized palliative care services. Adding the census data of palliative
      care units, the total estimated number of institutions with specialized
      palliative care services was 659. Of all the patients with cancer who died in the
      period from April 2009 to May 2010 in Japan, the estimated proportion who
      utilized specialized palliative care services was 24%. CONCLUSIONS: Usage of
      specialized palliative care services in Japan have increased explosively in the
      past decade.

PMID- 22949740
TI  - Effect of transradial coronary angiography procedure on vascular diameter and
      vasodilator functions in the access site.
AB  - The present study aimed to investigate the long-term effects of transradial
      procedures on the radial artery diameter and vasodilator properties. The study
      included a total of 35 patients (28 males and 7 females) who underwent left
      transradial coronary angiography with an appropriate indication. The radial
      artery diameters were measured before and after flow-mediated vasodilation (FMD)
      and nitrate-mediated vasodilation (NMD). The nonintervened right radial artery
      served as the control. A marked narrowing in the diameter of the intervened
      radial artery and impaired FMD response indicating endothelial dysfunction were
      observed at a mean of 9 months after transradial intervention. Structural and
      functional changes should be taken into consideration if previously intervened
      radial artery would be used for interventions, such as arterial bypass graft or
      dialysis fistula.

PMID- 22949741
TI  - Evaluating unfractionated heparin fixed dosing protocol and establishing an
      institutional therapeutic range for UFH in hospital setting in Jordan.
AB  - This study was conducted to evaluate current unfractionated heparin (UFH) dosing
      regimen and establish an institutional therapeutic range for UFH in a public
      hospital in Jordan. In the first part, medical records of 241 patients who
      received UFH were reviewed retrospectively. In the second part, blood samples
      were withdrawn from 60 patients on UFH, and activated partial thromboplastin time
      and anti-Xa assay were measured. Most activated partial thromboplastin time
      readings were not therapeutic (91.4%) and recurrence of thrombosis was reported
      in 35.3% of patients. In the second part, therapeutic activated partial
      thromboplastin time range corresponding to the UFH concentration of 0.3 to 0.7
      anti-factor Xa unit/mL was 56 to 95 seconds, which corresponds to an activated
      partial thromboplastin time range of 1.5 of 2.8 times the mean control value. The
      traditional activated partial thromboplastin time range ratio of 1.5 to 2.5 times
      the control value can result in subtherapeutic UFH levels. 

PMID- 22949742
TI  - Changing choices: disabled and chronically ill people's experiences of
      reconsidering choices.
AB  - OBJECTIVES: To increase understanding of disabled and chronically ill people's
      experiences of revisiting choices by considering events that prompted people to
      reconsider choices; what factors motivated them to act upon these events and what
      factors affected their experiences of revisiting choices. METHODS: A sub-sample
      of 20 disabled and chronically ill people who took part in a qualitative,
      longitudinal study exploring choice-making in the context of changing
      circumstances. Each person was interviewed three times. Analysis focussed on
      choices that people had been prompted to revisit. RESULTS: Most choices were
      about health or social care and were revisited within a year due to: changes in
      health or social circumstances; poorer than expected outcomes; and external
      interventions. People were motivated to make changes by a desire to maintain
      independence and control, but perceived short-term costs of decision-making could
      act as a deterrent. Experiences of revisiting choices were affected by help from
      other people and emotional strength. DISCUSSION: Making and revisiting choices is
      complex; people need support to engage with the continual cycle of choice-making.
      People who instigate revisions of their own accord may be particularly vulnerable
      to lack of support.

PMID- 22949743
TI  - Promoting first relationships: randomized trial of a relationship-based
      intervention for toddlers in child welfare.
AB  - We conducted a community-based, randomized control trial with intent-to-treat
      analyses of Promoting First Relationships (PFR) to improve parenting and toddler
      outcomes for toddlers in state dependency. Toddlers (10-24 months; N = 210) with
      a recent placement disruption were randomized to 10-week PFR or a comparison
      condition. Community agency providers were trained to use PFR in the intervention
      for caregivers. From baseline to postintervention, observational ratings of
      caregiver sensitivity improved more in the PFR condition than in the comparison
      condition, with an effect size for the difference in adjusted means
      postintervention of d = .41. Caregiver understanding of toddlers' social
      emotional needs and caregiver reports of child competence also differed by
      intervention condition postintervention (d = .36 and d = .42) with caregivers in
      the PFR condition reporting more understanding of toddlers and child competence.
      Models of PFR effects on within-individual change were significant for caregiver
      sensitivity and understanding of toddlers. At the 6-month follow-up, only 61% of
      original sample dyads were still intact and there were no significant differences
      on caregiver or child outcomes.

PMID- 22949744
TI  - Ozone Uptake During Inspiratory Flow in a Model of the Larynx, Trachea and
      Primary Bronchial Bifurcation.
AB  - Three-dimensional simulations of the transport and uptake of a reactive gas such
      as O(3) were compared between an idealized model of the larynx, trachea, and
      first bifurcation and a second "control" model in which the larynx was replaced
      by an equivalent, cylindrical, tube segment. The Navier-Stokes equations, Spalart
      Allmaras turbulence equation, and convection-diffusion equation were implemented
      at conditions reflecting inhalation into an adult human lung. Simulation results
      were used to analyze axial velocity, turbulent viscosity, local fractional
      uptake, and regional uptake. Axial velocity data revealed a strong laryngeal jet
      with a reattachment point in the proximal trachea. Turbulent viscosity data
      indicated that jet turbulence occurred only at high Reynolds numbers and was
      attenuated by the first bifurcation. Local fractional uptake data affirmed
      hotspots previously reported at the first carina, and suggested additional
      hotspots at the glottal constriction and jet reattachment point in the proximal
      trachea. These laryngeal effects strongly depended on inlet Reynolds number, with
      maximal effects (approaching 15%) occurring at maximal inlet flow rates. While
      the increase in the regional uptake caused by the larynx subsided by the end of
      the model, the effect of the larynx on cumulative uptake persisted further
      downstream. These results suggest that with prolonged exposure to a reactive gas,
      entire regions of the larynx and proximal trachea could show signs of tissue
      injury.

PMID- 22949745
TI  - A surge in the seroprevalence of toxoplasmosis among the residents of islands in
      Gangwha-gun, Incheon, Korea.
AB  - Seroepidemiological changes of Toxoplasma gondii infection among the residents of
      the islands of Gangwha-gun, Incheon for 2 years were surveyed and evaluated by
      ELISA using a crude extract antigen. In 2010, sera of 919 adult residents in
      Gyodong-myeon and 313 adults in Samsan-myeon were collected and checked for IgG
      antibody titers, which showed 14.5% (133 sera) and 19.8% (62 sera) positive
      rates, respectively. In 2011, sera of 955 adults in Gyodong-myeon and 341 adults
      in Samsan-myeon were examined, which showed an increase of positive rates to
      23.8% (227 sera) and 31.7% (108 sera), respectively. Totally, the seroprevalence
      of the first year was 15.8% and it increased rapidly to 25.8% in the second year.
      The positive rates of both sexes increased simultaneously with the significant
      ratio of males to females by 1.7-2.2 fold (P<0.05). In both myeons, 661 sera were
      collected every year and showed changes in optical density (OD) in 177 sera;
      newly found as positives in 73 persons (11.0%), negative conversion in 10 persons
      (1.5%), and maintained or increased in 94 persons (14.2%). This rapid increase in
      the prevalence of toxoplasmosis in Gangwha islands may be due to in part peculiar
      changes in the toxoplasmic environment of the islands and presumably the
      consumption of the pork bred domestically within the islands or imported from
      high endemic nations. It is necessary to find out symptomatic toxoplasmic
      patients and confirm the risk factors for further infection in the islands of
      Gangwha-gun.

PMID- 22949746
TI  - Real-time RT-PCR on SAG1 and BAG1 gene expression during stage conversion in
      immunosuppressed mice infected with Toxoplasma gondii Tehran strain.
AB  - Toxoplasmic encephalitis is caused by reactivation of bradyzoites to rapidly
      dividing tachyzoites of the apicomplexan parasite Toxoplasma gondii in
      immunocompromised hosts. Diagnosis of this life-threatening disease is
      problematic, because it is difficult to discriminate between these 2 stages.
      Toxoplasma PCR assays using gDNA as a template have been unable to discriminate
      between an increase or decrease in SAG1 and BAG1 expression between the active
      tachyzoite stage and the latent bradyzoite stage. In the present study, real-time
      RT-PCR assay was used to detect the expression of bradyzoite (BAG1)- and
      tachyzoite-specific genes (SAG1) during bradyzoite/tachyzoite stage conversion in
      mice infected with T. gondii Tehran strain after dexamethasone sodium phosphate
      (DXM) administration. The conversion reaction was observed in the lungs and brain
      tissues of experimental mice, indicated by SAG1 expression at day 6 after DXM
      administration, and continued until day 14. Bradyzoites were also detected in
      both organs throughout the study; however, it decreased at day 14 significantly.
      It is suggested that during the reactivation period, bradyzoites not only escape
      from the cysts and reinvade neighboring cells as tachyzoites, but also converted
      to new bradyzoites. In summary, the real-time RT-PCR assay provided a reliable,
      fast, and quantitative way of detecting T. gondii reactivation in an animal
      model. Thus, this method may be useful for diagnosing stage conversion in
      clinical specimens of immunocompromised patients (HIV or transplant patients) for
      early identification of tachyzoite-bradyzoite stage conversion.

PMID- 22949747
TI  - Comparative morphology of minute intestinal fluke eggs that can occur in human
      stools in the republic of Korea.
AB  - The egg morphology of minute intestinal flukes (MIF) that can occur as human
      infections in the Republic of Korea, i.e., Metagonimus yokogawai, M. miyatai, M.
      takahashii, Heterophyes nocens, Heterophyopsis continua, Stellantchasmus
      falcatus, Stictodora fuscata, Pygidiopsis summa, and Gymnophalloides seoi, was
      studied in comparison with Clonorchis sinensis. The adult worms were obtained
      from residents of endemic areas, and their intrauterine eggs were studied and
      measured using light microscopy; the length, width, length-width ratio (LWR), and
      Faust-Meleney index (FMI). Several specimens were processed for scanning electron
      microscopy (SEM), and before gold-coating, the uterine portion of each fluke was
      etched with a sharp pin in order to expose the eggs. The MIF eggs were ovoid,
      pyriform, or elliptical with a size range of 21-35*12-21 um. S. fuscata eggs
      revealed the highest FMI (largest in the area) and lowest LWR, whereas P. summa
      eggs showed the lowest FMI and medium LWR. SEM revealed that G. seoi and S.
      fuscata had remarkably clean shell surface lacking the muskmelon-like structure
      which is prominent in C. sinensis eggs. In Metagonimus spp., H. continua, H.
      nocens, and S. falcatus eggs, minute surface ridges were recognizable though less
      prominent compared with C. sinensis. On the surface of P. summa eggs, thread-like
      curly structures were characteristically seen. The results revealed that
      important differential keys for MIF eggs include the length, width, area (FMI),
      shape of the eggs, and the extent of the muskmelon-like structure or ridges on
      their shell surface and operculum.

PMID- 22949748
TI  - Infection status of estuarine fish and oysters with intestinal fluke
      metacercariae in Muan-gun, Jeollanam-do, Korea.
AB  - The source of human infection with intestinal flukes was surveyed in estuarine
      fishes, including the dotted gizzard shad, common sea bass, common blackish goby,
      redlip mullet, black sea bream, and oyster collected from Muan-gun, Jeollanam-do,
      Korea during August and September 2007. Collected fishes and oysters were
      artificially digested in pepsin-HCl solution and examined under a
      stereomicroscope. In 36 shads (Konosirus punctatus) and 20 basses (Lateolabrax
      japonicus) examined, Heterophyopsis continua metacercariae were found in 58.3%
      and 100%, and their average numbers were 12.0 and 6.3 per infected fish,
      respectively. In 34 gobies (Acanthogobius flavimanus) examined, metacercariae of
      H. continua were detected in 79.4%, Stictodora lari in 97.1%, and Acanthotrema
      felis in 92.1%, and their average numbers were 45.8, 189.3, and 235.3 per
      infected fish, respectively. In 37 redlip mullets (Chelon haematocheilus),
      Heterophyes nocens metacercariae were found in 56.8%, Pygidiopsis summa in 94.6%,
      and Stictodora fuscata in 45.9%, and the average metacercarial densities were
      17.4, 31.3, and 35.1 per infected fish, respectively. In 30 black sea breams
      (Acanthopagrus schlegeli) and 45 oysters (Crassostrea gigas) examined, no
      metacercariae were detected. From the above results, it has been confirmed that
      the dotted gizzard shad, common sea bass, common blackish goby, and redlip mullet
      from Muan-gun, Jeollanam-do, Korea are infected with the metacercariae of
      heterophyid flukes.

PMID- 22949749
TI  - The first human case of Thelazia callipaeda infection in Vietnam.
AB  - A 26-year-old man residing in a village of Thai Nguyen Province, North Vietnam,
      visited the Thai Nguyen Provincial Hospital in July 2008. He felt a bulge
      sticking pain in his left eye and extracted 5 small nematode worms by himself
      half a day before visiting the hospital. Two more worms were extracted from his
      left eye by a medical doctor, and they were morphologically observed and
      genetically analyzed on the mitochondrial cytochrome c oxidase 1 gene. The worms
      were 1 male and 1 female, and genetically identical with those of Thelazia
      callipaeda. By the present study, the presence of human T. callipaeda infection
      is first reported in Vietnam.

PMID- 22949750
TI  - Seroprevalence of toxoplasmosis in the residents of Cheorwon-gun, Gangwon-do,
      Korea.
AB  - The seroepidemiological status of toxoplasmosis was surveyed among the residents
      of Cheorwon-gun, Gangwon-do by means of ELISA using a crude extract antigen of
      Toxoplasma gondii. The sera of 1,661 adult residents (866 males and 795 females)
      were collected and checked for IgG antibody titers, which showed 17.0% positive
      rate (282 sera). The positive rate was significantly different between the sex;
      20.6% for males and 13.1% for females (P<0.05). The positive rates were higher in
      fifties of males (28.7%) and forties of females (20.0%). This positive rate of
      toxoplasmosis in Cheorwon-gun residents is regarded as the highest among the
      surveys of different geographical regions of Korea. This high positive rate may
      due in part to peculiar geographical locality of the surveyed area near the
      naturally well preserved demilitarized zone (DMZ) or presumably consumption of
      the pork imported from high endemic nations. Therefore, it is necessary to study
      further the epidemiology of toxoplasmosis in Cheorwon-gun.

PMID- 22949751
TI  - Detection of ocular Toxoplasma gondii infection in chronic irregular recurrent
      uveitis by PCR.
AB  - Toxoplasma gondii is a zoonotic parasite resulting in human infections and one of
      the infectious pathogens leading to uveitis and retinochoroiditis. The present
      study was performed to assess T. gondii infection in 20 ocular patients with
      chronic irregular recurrent uveitis (20 aqueous humor and 20 peripheral blood
      samples) using PCR. All samples were analyzed by nested PCR targeting a specific
      B1 gene of T. gondii. The PCR-positive rate was 25% (5/20), including 5% (1) in
      blood samples, 25% (5) in aqueous humor samples, and 5% (1) in both sample types.
      A molecular screening test for T. gondii infection in ocular patients with common
      clinical findings of an unclear retinal margin and an inflammatory membrane over
      the retina, as seen by fundus examination, may be helpful for early diagnosis and
      treatment.

PMID- 22949752
TI  - Production and evaluation of Toxoplasma gondii recombinant GRA7 for serodiagnosis
      of human infections.
AB  - The precise diagnosis of the acute toxoplasmosis in pregnant women and
      immunocompromsied patients has critical importance. Most of the commercially
      available assays use the whole Toxoplasma soluble extract as the antigen.
      However, the assays currently available for the detection of specific anti
      Toxoplasma antibodies may vary in their abilities to detect serum
      immunoglobulins, due to the lack of a purified standardized antigen. The aim of
      this study was production and evaluation of the usefulness of the recombinant
      Toxoplasma gondii GRA7 antigen for the serodiagnosis of Toxoplasma gondii IgM and
      IgG by ELISA. A total of 70 T. gondii IgM positive sera, 74 T. gondii IgG
      positive sera, and 60 sera from subjects who were not infected with T. gondii
      were examined. These sera were shown different absorbance values in ELISA test.
      To control the specificity of the rGRA7 other parasitic diseases, for example,
      echinococcosis, malaria, leishmaniasis, fascioliasis, and strongyloidiasis were
      tested of which none showed positive results. Sensitivity and specificity of the
      generated recombinant IgG ELISA in comparison with commercial ELISA (com ELISA)
      were 89% and 90%, and the sensitivity and specificity of the generated
      recombinant IgM ELISA were 96% and 90%, respectively. The results obtained here
      show that this antigen is useful for diagnostic purposes.

PMID- 22949753
TI  - Effect of temperature on embryonation of Ascaris suum eggs in an environmental
      chamber.
AB  - The influence of temperature on the development and embryonation of Ascaris suum
      eggs was studied using coarse sand medium in an environmental chamber with 50%
      humidity. The time required for development and embryonation of eggs was examined
      under 3 different temperature conditions, 5 degrees C, 25 degrees C, and 35
      degrees C. A. suum eggs did not develop over 1 month at the temperature of 5
      degrees C. However, other temperature conditions, 25 degrees C and 35 degrees C,
      induced egg development to the 8-cell-stage at days 5-6 after incubation. All
      eggs examined developed to the 8-cell stage at day 6 after incubation in the sand
      medium at 25 degrees C. The higher temperature, 35 degrees C, slightly
      accelerated the A. suum egg development compared to 25 degrees C, and the
      development to the 8-cell stage occurred within day 5 after incubation. The
      formation of larvae in A. suum eggs at temperatures of 35 degrees  and 25 degrees
      C appeared at days 17 and 19 after incubation, respectively. These findings show
      that 35 degrees  condition shortens the time for the development of A. suum eggs
      to the 8-cell-stage in comparison to 25 degrees C, and suggest the possibility of
      accelerated transmission of this parasite, resulting from global warming and
      ecosystem changes.

PMID- 22949754
TI  - Quantitative evaluation of viability- and apoptosis-related genes in Ascaris suum
      eggs under different culture-temperature conditions.
AB  - Ascaris suum eggs are inactivated by composting conditions; however, it is
      difficult to find functional changes in heat-treated A. suum eggs. Here,
      unembryonated A. suum eggs were incubated at 20 degrees C, 50 degrees C, and 70
      degrees C in vitro, and the gene expression levels related to viability, such as
      eukaryotic translation initiation factor 4E (IF4E), phosphofructokinase 1 (PFK1),
      and thioredoxin 1 (TRX1), and to apoptosis, such as apoptosis-inducing factor 1
      (AIF1) and cell death protein 6 (CDP6), were evaluated by real-time quantitative
      RT-PCR. No prominent morphological alterations were noted in the eggs at 20
      degrees C until day 10. In contrast, the eggs developed rapidly, and embryonated
      eggs and hatched larvae began to die, starting on day 2 at 50 degrees C and day 1
      at 70 degrees C. At 20 degrees C, IF4E, PFK1, and TRX1 mRNA expression was
      significantly increased from days 2-4; however, AIF1 and CDP6 mRNA expression was
      not changed significantly. IF4E, PFK1, and TRX1 mRNA expression was markedly
      decreased from day 2 at 50 degrees  and 70 degrees C, whereas AIF1 and CDP6 mRNA
      expression was significantly increased. The expressions of HSP70 and HSP90 were
      detected for 9-10 days at 20 degrees C, for 3-5 days at 50 degrees C, and for 2
      days at 70 degrees C. Taken together, incremental heat increases were associated
      with the rapid development of A. suum eggs, decreased expression of genes related
      to viability, and earlier expression of apoptosis-related genes, and finally
      these changes of viability- and apoptosis-related genes of A. suum eggs were
      associated with survival of the eggs under temperature stress.

PMID- 22949755
TI  - A seroepidemiological survey of toxocariasis among eosinophilia patients in
      Chungcheongnam-do.
AB  - There have been several reports on the relationship between toxocariasis and
      eosinophilia, but all have been limited to the areas of Seoul or Gangwon-do. In
      the present study, we investigated the seroprevalence of toxocariasis among
      eosinophilia patients in Chungcheongnam-do, the central district of Korea. Among
      the 101 patients tested, 51 (50.5%) were identified as positive by Toxocara
      ELISA, and 46 (45.5%) were confidently diagnosed with toxocariasis because of
      absence of any other cause of eosinophilia. Whereas 22 of 42 seropositive
      patients (52.3%) had a recent history of consuming raw livers, especially the cow
      liver, only 1 of 25 seronegative patients (4%) had done so (P<0.01). From these
      results, we could confirm that toxocariasis is related to eosinophilia, and infer
      that ingestion of raw cow liver plays a vital role in the transmission of
      toxocariasis in Chungcheongnam-do.

PMID- 22949756
TI  - Molecular identification of Oesophagostomum and Trichuris eggs isolated from wild
      Japanese macaques.
AB  - Natural habitat fragmentation and reducing habitat quality have resulted in an
      increased appearance of Japanese macaques, Macaca fuscata (Gray, 1870), in
      suburban areas in Japan. To investigate the risk of zoonotic infections, a
      coprological survey of helminth eggs passed by wild Japanese macaques was carried
      out in 2009 and 2010 in Shiga Prefecture, Japan. Microscopic examination found
      helminth eggs in high prevalence, and nucleotide sequencing of DNA extracted from
      the eggs identified Oesophagostomum cf. aculeatum and Trichuris trichiura. A
      fecal culture also detected infective larvae of Strongyloides fuelleborni. These
      zoonotic nematodes pose a potential health issue to local people in areas
      frequented by Japanese macaques.

PMID- 22949757
TI  - Prevalence of Enterobius vermicularis among preschool children in Muan-gun,
      Jeollanam-do, Korea.
AB  - We assessed the prevalence of Enterobius vermicularis infection and changes in
      the egg positive rate (EPR) over 1-year time, using the adhesive cellophane-tape
      perianal swab method in 2,347 preschool children in Muan-gun, Jeollanam-do,
      Republic of Korea in 2008 and 2009. The overall EPR for E. vermicularis was 4.1%
      in 2008 and 4.5% in 2009. A study population of 389 children was repeatedly
      examined for 2 years. Within this group, the EPR in 2009 was twice higher than in
      2008, and the EPR of the group of 5-7-year-old children was significantly higher
      than that of other age groups. Moreover, in the group of 5-7-year-old children in
      2009, the rates of positive and negative conversion were significantly higher and
      lower, respectively, than in other age groups. Conclusively, enterobiasis was
      prevalent during 2008-2009 among preschool children in Muan-gun, Jeollanam-do,
      and the increased EPR in 2009 was due to an increase in newly acquired infections
      among 5-7-year-old children.

PMID- 22949758
TI  - Two human cases infected by the horsehair worm, Parachordodes sp. (Nematomorpha:
      Chordodidae), in Japan.
AB  - The present study was performed to describe 2 human cases infected by the
      horsehair worm, Parachordodes sp., in Japan. Two gordiid worms were collected in
      the vomit and excreta of an 80-year-old woman in November 2009 in Kyoto city, and
      in the mouth of 1-year-old boy in December 2009 in Nara city, Japan,
      respectively. Both worms were males having bifurcated posterior ends and male
      gonads in cross sectional specimens. They were identified as Parachordodes sp.
      (Nematomorpha: Chordodidae) based on the characteristic morphologies of cross
      sections and areoles in the cuticle. DNA analysis on 18S rRNA partial sequence
      arrangements was also carried out and both worms were assumed to be close to the
      genus Paragordionus based on tree analysis, and far from Gordius sp. which has
      already been reported in humans in Japan. DNA sequencing of the Parachordodes
      worm does not appear on the database; therefore, more information on the gene
      sequences of the genus Parachordodes from humans, animals, or intermediates is
      required.

PMID- 22949759
TI  - Echinostome flukes receovered from humans in Khammouane Province, Lao PDR.
AB  - Echinostome eggs were detected in 22 (1.1%) of 2,074 people residing in riparian
      villages along the Mekong River in Khammouane Province, Lao PDR. In order to
      recover the adult flukes, 9 persons were treated with praziquantel and purged
      with magnesium salts. A total of 55 echinostome specimens (4 species) were
      recovered from the 9 persons. Echinostoma revolutum (8 specimens) was recovered
      from 3 persons, Artyfechinostomum malayanum (8 specimens) was from 2 persons,
      Echinochasmus japonicus (33 specimens) was from 7 persons, and Euparyphium sp. (6
      specimens) was from 1 person. In Lao PDR, only human infections with E. japonicus
      were previously known. Therefore, the present study describes human infections
      with E. revolutum, A. malayanum, and Euparyphium sp. for the first time in Lao
      PDR. These results indicate that the surveyed villages of Khammouane Province,
      Lao PDR are low-grade endemic foci of echinostomiasis.

PMID- 22949760
TI  - Discovery of Endocotyle incana and Spelotrema pseudogonotyla (Digenea:
      Microphallidae) from scolopacid migratory birds in Korea.
AB  - Migratory birds have been suspected as playing a central role in transmission of
      various trematodes, but few surveys have been undertaken in the Republic of
      Korea. In the present study, we describe new fauna of microphallid flukes in
      Korea. Two species of microphallids were found in the intestines of 2 migratory
      bird species, namely the red necked stints (Calidris ruficollis) and the terek
      sandpiper (Xenus cinereus), in a coastal area of Gunsan-si, Jeollabuk-do. The
      microphallids recovered from the latter were 451 um in length and 217 um in
      width, and the eggs were very small, 13 um by 8 um. They had the characteristic
      extracecal vitellaria intruding into the median posttesticular area, belonging to
      Endocotyle incana. Another microphallids were discovered from both migratory
      birds, 417 um in length and 249 um in width. The cirrus was projecting into the
      genital atrium in form of male papilla, and bounded by a muscular flap, termed
      pseudogonotyl. They were identified as Spelotrema pseudogonotyla in consideration
      of the distinctive male papilla and pseudogonotyl. Besides these flukes,
      Maritrema obstipum and Gynaecotyla squatarolae also were recovered. This paper is
      in fact the first report on the presence of Spelotrema and Endocotyle in Korea.

PMID- 22949761
TI  - Reliance.

PMID- 22949762
TI  - Dizzy medical writing and editing: time for a lockout?

PMID- 22949763
TI  - Carotid artery stenting versus endarterectomy: a systematic review.
AB  - For about 2 decades, investigators have been comparing carotid endarterectomy
      with carotid artery stenting in regard to their effectiveness and safety in
      treating carotid artery stenosis. We conducted a systematic review to summarize
      and appraise the available evidence provided by randomized trials, meta-analyses,
      and registries comparing the clinical outcomes of the 2 procedures. We searched
      the MEDLINE, SciVerse Scopus, and Cochrane databases and the bibliographies of
      pertinent textbooks and articles to identify these studies. The results of
      clinical trials and, consequently, the meta-analyses of those trials produced
      conflicting results regarding the comparative effectiveness and safety of carotid
      endarterectomy and carotid stenting. These conflicting results arose because of
      differences in patient population, trial design, outcome measures, and
      variability among centers in the endovascular devices used and in operator
      skills. Careful appraisal of the trials and meta-analyses, particularly the most
      recent and largest National Institutes of Health-sponsored trial (the Carotid
      Revascularization Endarterectomy vs Stenting Trial [CREST]), showed that carotid
      stenting and endarterectomy were associated with similar rates of death and
      disabling stroke. Within the 30-day periprocedural period, carotid stenting was
      associated with higher risks of stroke, especially for patients aged >70 years,
      whereas carotid endarterectomy was associated with a higher risk of myocardial
      infarction. The slightly higher cost of stenting compared with endarterectomy was
      within an acceptable range by cost-effectiveness standards. We conclude that
      carotid artery stenting is an equivalent alternative to carotid endarterectomy
      when patient age and anatomy, surgical risk, and operator experience are
      considered in the choice of treatment approach.

PMID- 22949764
TI  - Cellular retrograde cardiomyoplasty and relaxin therapy for postischemic
      myocardial repair in a rat model.
AB  - We sought to determine whether skeletal myoblasts, wild-type or engineered to
      express relaxin, might improve myocardial viability and performance in a rat
      model of chronic myocardial infarction. Our purpose was to investigate a
      potential new therapy for heart failure. From October 2005 through September
      2009, we surgically induced acute myocardial infarction in 80 male Wistar rats.
      Thirty days after surgery, the rats underwent reoperation for the retrograde
      coronary venous infusion of skeletal myoblasts, relaxin, or both. The animals
      were randomly assigned to 4 experimental groups: R1 (the control group, which
      underwent saline-solution infusion), R2 (systemic relaxin therapy), R3 (myoblast
      infusion), and R4 (myoblast infusion and systemic relaxin therapy).
      Echocardiography, positron emission tomography, and cellular and histologic
      analysis were performed at 4 established time points. Mortality rates were
      similar among the groups. Postinfarction echocardiographic evaluation revealed
      similar left ventricular dysfunction. Viable myocardium, evaluated with positron
      emission tomography, was analogous. After therapy, the echocardiographic values
      of cardiac function improved significantly (P<0.05) in all groups except R1.
      Myocardial viability volume increased significantly in groups R3 and R4 (P<0.05)
      but was unchanged in groups R2 and R1. In group R4, the echocardiographic and
      positron emission tomographic results improved significantly (P<0.001).
      Histologic analysis showed that myoblasts settled in regions of ischemic
      scarring, especially when combined with relaxin. The retrograde venous route is
      safe, effective, and clinically feasible for cell delivery. Myoblasts and relaxin
      are better than either alone in terms of myocardial viability and performance
      improvement.

PMID- 22949765
TI  - Potential role of plasma myeloperoxidase level in predicting long-term outcome of
      acute myocardial infarction.
AB  - We investigated the prognostic importance of plasma myeloperoxidase levels in
      patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up,
      and we analyzed the correlations between plasma myeloperoxidase levels and other
      biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 +/
      11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control
      participants. Patients were divided into 2 groups according to the median
      myeloperoxidase level (Group 1: plasma myeloperoxidase <= 68 ng/mL; and Group 2:
      plasma myeloperoxidase > 68 ng/mL). Patients were monitored for the occurrence of
      major adverse cardiovascular events (MACE), which were defined as cardiac death;
      reinfarction; new hospital admission for angina; heart failure; and
      revascularization procedures. The mean follow-up period was 25 +/- 16 months.
      Plasma myeloperoxidase levels were higher in STEMI patients than in control
      participants (82 +/- 34 vs 20 +/- 12 ng/mL; P = 0.001). Composite MACE occurred
      in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low
      myeloperoxidase levels (11%) (P = 0.02). The incidences of nonfatal recurrent
      myocardial infarction and verified cardiac death were higher in the high
      myeloperoxidase group. In multivariate analysis, high plasma myeloperoxidase
      levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence
      interval, 1.625-6.563; P = 0.003). High plasma myeloperoxidase levels identify
      patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation
      of plasma myeloperoxidase levels might be useful in determining patients at high
      risk of death and MACE who can benefit from further aggressive treatment and
      closer follow-up.

PMID- 22949766
TI  - Subxiphoid versus intercostal chest tubes: comparison of postoperative pain and
      pulmonary morbidities after coronary artery bypass grafting.
AB  - Chest tubes are one cause of pain after cardiac surgery. In a prospective,
      randomized study, we investigated the effects of the position of chest tubes on
      acute postoperative pain and pulmonary morbidities in patients who underwent
      coronary artery bypass grafting. From June through December 2010, 40 patients who
      underwent elective coronary artery bypass grafting were enrolled in the study. We
      investigated 2 randomized groups of patients: Group 1 (n-20) had a left chest
      tube inserted through the midline inferior to the xiphoid process (subxiphoid
      approach), and Group 2 (n-20) had a left chest tube inserted through the 6th
      intercostal space along the anterior axillary line (intercostal approach). We
      compared the results with respect to postoperative pain, the need for analgesic
      agents, chest-tube drainage, pulmonary morbidities, and duration of
      hospitalization. The intensity of postoperative pain was similar between the
      groups. The cumulative doses of analgesic agents, incidence of pulmonary
      morbidities, and duration of hospitalization were also similar. Pleural effusion
      and atelectasis were each diagnosed in 3 patients in Group 1 (15%) and 1 patient
      in Group 2 (5%) (both P=0.68). Two of the patients in Group 1 required drainage
      of the pleural effusion. In our study, we found that the subxiphoid and
      intercostal approaches for chest-tube placement yielded similar clinical
      outcomes.

PMID- 22949767
TI  - Nitinol thermoreactive clips for secondary sternal closure in cases of
      noninfective sternal dehiscence.
AB  - Postoperative sternal dehiscence is a potentially catastrophic sequela to median
      sternotomy that can cause not only chest-wall discomfort and pulmonary
      dysfunction but infection, both superficial and mediastinal. Nitinol
      thermoreactive clips use a novel material in the treatment of sternal dehiscence.
      We sought to determine whether the use of these clips is an effective remedy for
      noninfective sternal dehiscence. From January 2008 through December 2011, we
      retrospectively studied the data on 10 patients whose sternums had been closed
      with nitinol thermoreactive clips after the development of noninfective sternal
      dehiscence. Diagnosis was made on the bases of clinical criteria, chest
      radiography, and microbiological investigation. There was no control group. No
      procedure-related sequelae occurred. There was no recurrent sternal instability
      and dehiscence, sternal-related hemorrhage, superficial wound infection, or
      mediastinal infection. We believe that the use of nitinol thermoreactive clips is
      a safe, easy, and efficient method of secondary sternal closure for noninfective
      sternal dehiscence.

PMID- 22949768
TI  - Anticoagulants for stroke prevention in nonvalvular atrial fibrillation: new
      agents and an updated understanding.

PMID- 22949769
TI  - Outflow tract ventricular tachycardia.

PMID- 22949770
TI  - Ventricular tachycardias in the setting of cardiomyopathy: approaches to
      ablation.

PMID- 22949771
TI  - Antiarrhythmic therapy in atrial fibrillation: indications, guidelines, and
      safety.

PMID- 22949772
TI  - Exclusion of the left atrial appendage to prevent stroke in cases of atrial
      fibrillation.

PMID- 22949773
TI  - Benign or malignant anomaly? Very high takeoff of the left main coronary artery
      above the left coronary sinus.
AB  - Very high takeoff of the left main coronary artery in the absence of another
      coronary anomaly is a rare finding. The pathologic consequences of this anomaly
      are unclear, and the literature on this subject does not agree on whether the
      condition is dangerous. We present our findings in 2 patients who were discovered
      to have this anomaly upon noninvasive computed tomographic coronary angiography,
      and we discuss our analysis of the literature and our management of these
      patients.

PMID- 22949774
TI  - Continuous-flow total heart replacement device implanted in a 55-year-old man
      with end-stage heart failure and severe amyloidosis.
AB  - We implanted a continuous-flow total heart replacement device in a 55-year-old
      man who had severe end-stage heart failure due to amyloidosis and no other
      options for treatment. The device was composed of 2 modified HeartMate II
      ventricular assist pumps. After the implantation, our patient recovered normal
      neurologic function and was able to converse with his family and work on his
      computer. He died of multisystem organ failure caused by severe amyloidosis 5
      weeks after the implantation. During the past 6 years, we have been developing
      and testing various technological iterations for total heart replacement in our
      animal laboratory and have achieved survival periods as long as 90 days in
      calves. We describe the development, preclinical trials, and adaptation for human
      use of the modified HeartMate II apparatus, as well as its role in our patient's
      survival.

PMID- 22949775
TI  - Cleft posterior mitral valve leaflet in an adult with Turner syndrome diagnosed
      with the use of 3-dimensional transesophageal echocardiography.
AB  - Turner syndrome is a monosomy (45,X karyotype) in which the prevalence of
      cardiovascular anomalies is high. However, this aspect of Turner syndrome has
      received little attention outside of the pediatric medical literature, and the
      entire spectrum of cardiovascular conditions in adults remains unknown. We
      present the case of a 34-year-old woman who had Turner syndrome. When she was a
      teenager, her native bicuspid aortic valve was replaced with a mechanical
      prosthesis. Fifteen years later, during preoperative examination for prosthesis
      patient mismatch, severe mitral regurgitation was detected, and a congenital
      cleft in the posterior leaflet of the mitral valve was diagnosed with use of 3
      dimensional transesophageal echocardiography. The patient underwent concurrent
      mitral valve repair and aortic valve replacement. To our knowledge, this is the
      first report of a cleft in the posterior mitral valve leaflet as a cardiovascular
      defect observed in Turner syndrome, and the first such instance to have been
      diagnosed with the use of 3-dimensional echocardiography.

PMID- 22949776
TI  - Multiple left ventricular thrombi in a patient with left ventricular
      noncompaction.
AB  - The major clinical features of myocardial noncompaction are heart failure,
      arrhythmias, and thromboembolic events. Prominent myocardial trabeculae and deep
      recesses characteristic of myocardial noncompaction can cause stagnant blood flow
      and the formation of left ventricular clots. We describe the case of a 62-year
      old woman who presented with symptoms of heart failure secondary to left
      ventricular noncompaction. Transthoracic and transesophageal echocardiography
      revealed multiple left ventricular thrombi, which had formed despite the
      patient's long-term therapy with aspirin. Anticoagulative therapy should be
      considered for patients with myocardial noncompaction who also have risk factors
      for thromboembolism, such as atrial fibrillation, a history of systemic embolism,
      or severe left ventricular systolic dysfunction. However, chronic antiplatelet
      therapy may not sufficiently prevent clot formation in patients who have
      myocardial noncompaction and severe left ventricular systolic dysfunction.

PMID- 22949777
TI  - Remission of chronic anthracycline-induced heart failure with support from a
      continuous-flow left ventricular assist device.
AB  - We report the case of a patient who had chronic anthracycline-induced
      cardiomyopathy that was reversed after treatment with a left ventricular assist
      device. A 29-year-old woman had undergone anthracycline-based chemotherapy as a
      teenager in 1991 and 1992 and received a diagnosis of dilated cardiomyopathy 10
      years later. Optimal medical therapy had initially controlled the symptoms of
      heart failure. However, in June 2006, the symptoms worsened to New York Heart
      Association functional class IV status. We implanted a continuous-flow left
      ventricular assist device as a bridge to cardiac transplantation; of note, a left
      ventricular core biopsy at that time showed no replacement fibrosis. The
      patient's clinical status improved thereafter, enabling left ventricular assist
      device ex-plantation after 17 months. To our knowledge, this is the first report
      of the use of left ventricular assist device support to reverse chronic
      anthracycline-induced heart failure.

PMID- 22949778
TI  - A rare case of isolated congenital right ventricular inflow obstruction due to
      the presence of an intraventricular muscular shelf.
AB  - A 56-year-old man presented with anasarca and a 40-lb weight gain that had
      occurred over the course of 3 to 4 weeks. He had a history of permanent atrial
      fibrillation and a congenital anomaly of the right ventricular inflow tract. This
      defect consisted of a muscular shelf in the right ventricular inflow tract, which
      encased the tricuspid subvalvular apparatus in such a manner that it created
      tricuspid stenosis. The clinical consequences of this anatomic and hemodynamic
      situation were a massively dilated right atrium, permanent atrial fibrillation,
      and clinical evidence of right-sided heart failure, including fluid retention and
      ascites. The patient underwent surgical resection of the muscular shelf, which
      was followed by progressive resolution of the ascites and fluid retention.

PMID- 22949779
TI  - Percutaneous stenting to treat pulmonary vein stenosis after single-lung
      transplantation.
AB  - Pulmonary vein stenosis after lung transplantation is rare. Untreated, it can
      cause transplant failure and death. We describe the case of a 56-year-old man in
      whom pulmonary vein stenosis developed after single-lung transplantation. He was
      successfully treated with angioplasty and stent implantation guided by
      intravascular ultrasonography. To our knowledge, this is the first report of
      using this method to evaluate the pulmonary vein after lung transplantation, to
      confirm the diagnosis of pulmonary vein stenosis, and to guide the sizing and
      positioning of a stent. In lung-transplant recipients, percutaneous stent
      implantation may preclude reoperation and salvage the transplanted lung when used
      as treatment for pulmonary vein stenosis.

PMID- 22949780
TI  - Early cardiac metastasis from squamous cell carcinoma of the tongue in 2
      patients.
AB  - Cardiac metastasis from primary tumors is rare. Cardiac metastasis from squamous
      cell carcinoma of the tongue is rare; in the English-language medical literature,
      we read of only 4 patients with this condition. Here, we discuss the cases of 2
      such patients who presented at our institution only a few months apart. In both,
      with the use of 2-dimensional echocardiography, we incidentally found cardiac
      metastasis from squamous cell carcinoma of the tongue. Resection of the cardiac
      masses was precluded. These cases illustrate the usefulness of early cardiac
      evaluation with 2-dimensional echocardiography in patients with head and neck
      cancer and known metastatic disease.

PMID- 22949781
TI  - Marked attenuation of shock burden by the use of antitachycardia pacing therapy
      in a patient with an implanted cardioverter-defibrillator.
AB  - A 76-year-old man was admitted to our institution for elective exchange of his
      implanted cardioverter-defibrillator generator. Nine years earlier, he had been
      diagnosed with nonischemic cardiomyopathy and nonsustainable ventricular
      tachycardia. At that time, he had received a single-chamber implanted
      cardioverter-defibrillator, which was upgraded to a dual-chamber implanted
      cardioverter-defibrillator 3 years later. In the course of the current admission,
      routine device interrogation during exchange of the patient's implanted
      cardioverter-defibrillator generator revealed 150 episodes of ventricular
      tachycardia in the preceding 7 months, 137 of which had been successfully treated
      by antitachycardia pacing therapy without shock. These findings show the
      remarkable effectiveness of antitachycardia pacing in terminating ventricular
      tachycardia while preventing the delivery of shocks, minimizing patient
      discomfort, and avoiding implanted cardioverter-defibrillator battery depletion.

PMID- 22949782
TI  - Aberrant right subclavian artery-esophageal fistula and severe gastrointestinal
      bleeding after surgical correction of scimitar syndrome.
AB  - Scimitar syndrome and gastrointestinal bleeding from an aberrant right subclavian
      artery-esophageal fistula are each extremely rare. Although scimitar syndrome and
      aberrant right subclavian artery are typically asymptomatic in adults, fistulous
      connection between the aberrant artery and the esophagus is associated with a
      poor prognosis. Outcomes are contingent upon timely diagnosis and prompt surgical
      repair. Prolonged nasogastric and endotracheal intubation can lead to
      gastrointestinal bleeding in patients who have an aberrant right subclavian
      artery or other vascular ring. We recommend neither embolization nor the use of
      endovascular stents as anything other than a temporizing measure in the
      management of aberrant right subclavian artery injury. These methods can stop
      acute hemorrhage; however, sentinel bleeding will eventually occur and require
      definitive ligation. We report the case of a 57-year-old woman in whom an
      aberrant right subclavian artery-esophageal fistula developed after surgical
      correction of symptomatic scimitar syndrome. Massive gastrointestinal bleeding
      resulted from prolonged nasogastric and endotracheal intubation. To our
      knowledge, this is the first report of aberrant right subclavian artery and
      scimitar syndrome in the same patient, and the 4th report of a patient's
      surviving a fistula between the aberrant artery and the esophagus.

PMID- 22949783
TI  - Hyperinsulinemia euglycemia therapy for calcium channel blocker overdose: a case
      report.
AB  - We report the case of a patient with calcium channel blocker toxicity who was
      treated successfully with hyperinsulinemia euglycemia therapy, without prior use
      of vasopressors. The patient was a 60-year-old man with schizoaffective disorder
      who presented with severe hemodynamic compromise after an intentional overdose of
      5,400 mg of extended-release diltiazem. He had been admitted to the hospital
      twice before for attempted suicide with diltiazem and nifedipine, respectively.
      During the previous admissions, conventional treatments were used, and
      complications included hemodynamic compromise, ischemic bowel requiring
      ileostomy, and a prolonged hospital stay. During the current admission, the
      patient's clinical condition failed to improve after treatment with charcoal,
      fluid resuscitation, calcium, and glucagon. Eight hours after admission,
      hyperinsulinemia euglycemia therapy was initiated; 3 hours later, the patient's
      hemodynamic status showed sustained improvement. His bradycardia and hypotension
      resolved without cardiac pacing or vasopressors. Hyperinsulinemia euglycemia
      therapy is a potentially life-saving treatment for calcium channel blocker
      toxicity. We suggest that such therapy should be considered early, in conjunction
      with conventional therapy, for the treatment of calcium channel blocker overdose
      in patients not responding to initial treatment.

PMID- 22949784
TI  - Surgical repair of right atrial wall rupture after blunt chest trauma.
AB  - Right atrial wall rupture after blunt chest trauma is a catastrophic event
      associated with high mortality rates. We report the case of a 24-year-old woman
      who was ejected 40 feet during a motor vehicle accident. Upon presentation, she
      was awake and alert, with a systolic blood pressure of 100 mmHg. Chest computed
      tomography disclosed a large pericardial effusion; transthoracic echocardiography
      confirmed this finding and also found right ventricular diastolic collapse. A
      diagnosis of cardiac tamponade with probable cardiac injury was made; the patient
      was taken to the operating room, where median sternotomy revealed a 1-cm
      laceration of the right atrial appendage. This lesion was directly repaired with
      4-0 polypropylene suture. Her postoperative course was uneventful, and she
      continued to recover from injuries to the musculoskeletal system. This case
      highlights the need for a high degree of suspicion of cardiac injuries after
      blunt chest trauma. An algorithm is proposed for rapid recognition, diagnosis,
      and treatment of these lesions.

PMID- 22949785
TI  - Minimally invasive retrieval of patent foramen ovale closure device after device
      migration to the descending aorta.
AB  - Percutaneous treatment of patent foramen ovale with a septal closure device has
      become a common procedure, but it is associated with various complications.
      Migration of the device is uncommon, and migration through the aortic valve into
      the aorta is rare. Managing the migration of a patent foramen ovale occluder can
      be challenging; it usually requires surgical retrieval of the foreign body. We
      report a rare case in which a patient experienced migration of a large patent
      foramen ovale closure device to the descending aorta. Rarer still was its
      successful percutaneous management.

PMID- 22949786
TI  - Descending aorta-to-coronary artery bypass graft imaging by means of multislice
      computed tomography.

PMID- 22949787
TI  - Biventricular intracardiac device implanted in a patient with persistent left
      superior vena cava.

PMID- 22949788
TI  - Jazz musician hangs by a string.

PMID- 22949789
TI  - Aortic valve perforation diagnosed with use of 3-dimensional transesophageal
      echocardiography.

PMID- 22949790
TI  - Endovascular treatment of a mobile thrombus of the thoracic aorta in association
      with ulcerative colitis.

PMID- 22949791
TI  - Surviving a rare event: left main coronary artery occlusion.

PMID- 22949792
TI  - Optical coherence tomography-guided left main stem stenting: a new approach?

PMID- 22949793
TI  - Left anterior descending coronary artery muscular bridge: lengthy and complete.

PMID- 22949794
TI  - Medical education on the brink.

PMID- 22949795
TI  - Medical education on the brink.

PMID- 22949796
TI  - Medical education on the brink.

PMID- 22949797
TI  - Carbohydrate antigen-125 is a mirror of both left and right sides of the heart.

PMID- 22949798
TI  - Hemostatic modifications of the Bentall procedure.

PMID- 22949800
TI  - Contributions to the Improvement of Living Conditions among Neglected Populations
      with Trachoma.
AB  - OBJECTIVE: Trachoma (Chlamydia-triggered blinding infection) provoked
      irreversible visual impairment in about 8 million people in 2011, and the
      prevalence among children with dirty faces is more than three fold that among
      children with clean faces. In 250 villages with a high prevalence of trachoma
      (Kolofata district, Far North Region, Cameroon), the lack of water for facial
      cleanliness was reported during trachoma awareness campaigns. The objective of
      this study was to determine if the lack of water was linked with the absence of
      means to dig wells. METHODS: Wells, waterholes, motorcycles, irrigation pumps,
      electricity, goats and oxen, cell phones and distance from waterholes were
      recorded in January 2011 in 50 randomized villages of Kolofata's district.
      RESULTS: The number of villages with <25 goats and <5 oxen was 0 and the number
      of adults owning <1 goat was 0. The cost of a pail of water was 0.01 USD.
      Motorcycles, cell phones and televisions have been reported in more than 66% of
      villages. The cost for the construction of lined shaft wells ranged between 15-35
      goats and 0.5-3 oxen; the cost for drinking water wells ranged between 50-200
      goats and 3-30 oxen. DISCUSSION: No link between the means for digging wells at
      the village level and access to water was found. Social solidarity, which refers
      to a social debt owed by each person to his/her group, should be added to
      training guides to gauge its ability to release people from the dead end of
      having to wait for external assistance to gain access to water.

PMID- 22949801
TI  - Clinical and microbiological assessment of trachoma in the kolofata health
      district, far north region, cameroon.
AB  - BACKGROUND AND AIMS: Trachoma is a sight-threatening process triggered by the
      infection of the conjunctiva with Chlamydiae. Blindness associated with trachoma
      was reported in Sahelian areas of Cameroon. However, data on the prevalence of
      this neglected infection in the Far North Region are not available. The aim of
      this study was a) to assess clinical trachoma and b) to detect Chlamydia in the
      conjunctiva of trachomatous populations living in the Far North Regions of
      Cameroon. METHODS: A total of 2,423 randomly selected children (1-10 years) and
      1,590 women over 14 from randomly selected villages from the Kolofata Health
      District (115,000 inhabitants) were included in a cross-sectional study in
      February 2009. Trained staff examined and obtained conjunctival swabs from
      trachomatous subjects. DNA was extracted and amplified to detect Chlamydia DNA by
      real-time PCR. The quality of sampling was assessed by quantifying the number of
      epithelial cells. RESULTS: Children (2,397 or 98.9% of the predicted number) and
      women (1,543; 97.0%) were examined. The prevalence of follicular trachoma (TF) in
      children was 21% (95% CI 17.8-24.5) and of intense inflammatory trachoma (TI)
      5.2% (95% CI 3.6-7.3). Among the women, trichiasis (TT) was observed in 3.4% (95%
      CI 2.4-4.7), corneal opacities (CO) in 1.4% (95% CI 0.8-2.3) and trachoma-related
      blindness in 0.9% (95% CI 0.4-1.8). Conditions related to income, illiteracy,
      latrines, water supply and animals wandering close to dwellings were similar in
      all the villages. PCR was positive in 35% of children with active trachoma and in
      6% of adult females presenting TT and/or related corneal opacities. CONCLUSION:
      The prevalence of trachoma and the severe trachoma sequelae found during this
      survey underline the urgent need to implement efficient blindness prevention
      interventions to improve the visual future of the people in the Sahelian region.

PMID- 22949802
TI  - Paradoxical tuberculomas after completion of antituberculous treatment.
AB  - Paradoxical reactions in tuberculosis have been reported in patients with
      tuberculous meningitis and appear as intracranial tuberculomas within 14-270 days
      of starting antituberculous therapy (ATT). Paradoxical reactions are due to the
      immune response of the host to ATT. They are commonly seen in the intensive phase
      of chemotherapy. However, paradoxical reactions occurring after completion of ATT
      are rare. We report 2 patients with tuberculous meningitis who had already
      completed ATT and then developed tuberculomas.

PMID- 22949803
TI  - Pancreatitis and MODS Due to Scrub Typhus and Dengue Co-Infection.
AB  - We report a 40 year old woman admitted with an acute abdomen. Investigations
      revealed pancreatitis, bilateral pleural effusion, renal failure, disseminated
      intravascular coagulation, and scrub IgM ELISA and dengue NS1 positivity. She
      improved with azithromycin and appropriate pain and fluid management. She also
      developed central venous catheter-related MRSA sepsis that was managed in the
      hospital.

PMID- 22949804
TI  - Early amyloidogenic oligomerization studied through fluorescence lifetime
      correlation spectroscopy.
AB  - Amyloidogenic protein aggregation is a persistent biomedical problem. Despite
      active research in disease-related aggregation, the need for multidisciplinary
      approaches to the problem is evident. Recent advances in single-molecule
      fluorescence spectroscopy are valuable for examining heterogenic biomolecular
      systems. In this work, we have explored the initial stages of amyloidogenic
      aggregation by employing fluorescence lifetime correlation spectroscopy (FLCS),
      an advanced modification of conventional fluorescence correlation spectroscopy
      (FCS) that utilizes time-resolved information. FLCS provides size distributions
      and kinetics for the oligomer growth of the SH3 domain of alpha-spectrin, whose
      N47A mutant forms amyloid fibrils at pH 3.2 and 37  degrees C in the presence of
      salt. The combination of FCS with additional fluorescence lifetime information
      provides an exciting approach to focus on the initial aggregation stages,
      allowing a better understanding of the fibrillization process, by providing
      multidimensional information, valuable in combination with other conventional
      methodologies.

PMID- 22949805
TI  - Scutellaria barbata D. Don inhibits tumor angiogenesis via suppression of
      Hedgehog pathway in a mouse model of colorectal cancer.
AB  - Angiogenesis, which plays a critical role during tumor development, is tightly
      regulated by the Sonic Hedgehog (SHH) pathway, which has been known to
      malfunction in many types of cancer. Therefore, inhibition of angiogenesis via
      modulation of the SHH signaling pathway has become very attractive for cancer
      chemotherapy. Scutellaria barbata D. Don (SB) has long been used in China to
      treat various cancers including colorectal cancer (CRC). Our published data
      suggested that the ethanol extract of SB (EESB) is able to induce apoptosis of
      colon cancer cells and inhibit angiogenesis in a chick embryo chorioallantoic
      membrane model. To further elucidate the precise mechanisms of its anti-tumor
      activity, in the present study we used a CRC mouse xenograft model to evaluate
      the effect of EESB on tumor growth and angiogenesis in vivo. Our current data
      indicated that EESB reduces tumor size without affecting on the body weight gain
      in CRC mice. In addition, EESB treatment suppresses the expression of key
      mediators of the SHH pathway in tumor tissues, which in turn resulted in the
      inhibition of tumor angiogenesis. Furthermore, EESB treatment inhibits the
      expression of vascular endothelial growth factor A (VEGF-A), an important target
      gene of SHH signaling and functioning as one of the strongest stimulators of
      angiogenesis. Our findings suggest that inhibition of tumor angiogenesis via
      suppression of the SHH pathway might be one of the mechanisms by which
      Scutellaria barbata D. Don can be effective in the treatment of cancers.

PMID- 22949806
TI  - Micelle and bilayer formation of amphiphilic janus particles in a slit-pore.
AB  - We employ molecular dynamics simulations to investigate the self-assembly of
      amphiphilic Janus particles in a slit-pore consisting of two plane-parallel, soft
      walls. The Janus particles are modeled as soft spheres with an embedded unit
      vector pointing from the hydrophobic to the hydrophilic hemisphere. The structure
      formation is analyzed via cluster size distributions, density and polarization
      profiles, and in-plane correlation functions. At low temperatures and densities,
      the dominating structures are spherical micelles, whereas at higher densities we
      also observe wall-induced bilayer formation. Finally, we compare the MD results
      with those from a previous density functional study.

PMID- 22949807
TI  - Pre-ischemic treadmill training for prevention of ischemic brain injury via
      regulation of glutamate and its transporter GLT-1.
AB  - Pre-ischemic treadmill training exerts cerebral protection in the prevention of
      cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate
      release following ischemic stroke. However, the underlying mechanism of this
      process remains unclear. Cerebral ischemia-reperfusion injury was observed in a
      rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid
      was collected using the microdialysis sampling method, and the concentration of
      glutamate was determined every 40 min from the beginning of ischemia to 4 h after
      reperfusion with high-performance liquid chromatography (HPLC)-fluorescence
      detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate
      transporter-1 (GLT-1) protein in brain tissues was determined by Western blot
      respectively. The effect of pre-ischemic treadmill training on glutamate
      concentration and GLT-1 expression after cerebral ischemia in rats along with
      changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia
      yields critical information necessary to understand the protection mechanism
      exhibited by pre-ischemic treadmill training. The results demonstrated that pre
      ischemic treadmill training up-regulates GLT-1 expression, decreases
      extracellular glutamate concentration, reduces cerebral infarct volume, and
      improves neurobehavioral score. Pre-ischemic treadmill training is likely to
      induce neuroprotection after cerebral ischemia by regulating GLT-1 expression,
      which results in re-uptake of excessive glutamate.

PMID- 22949808
TI  - Expression patterns, activities and carbohydrate-metabolizing regulation of
      sucrose phosphate synthase, sucrose synthase and neutral invertase in pineapple
      fruit during development and ripening.
AB  - Differences in carbohydrate contents and metabolizing-enzyme activities were
      monitored in apical, medial, basal and core sections of pineapple (Ananas comosus
      cv. Comte de paris) during fruit development and ripening. Fructose and glucose
      of various sections in nearly equal amounts were the predominant sugars in the
      fruitlets, and had obvious differences until the fruit matured. The large rise of
      sucrose/hexose was accompanied by dramatic changes in sucrose phosphate synthase
      (SPS) and sucrose synthase (SuSy) activities. By contrast, neutral invertase (NI)
      activity may provide a mechanism to increase fruit sink strength by increasing
      hexose concentrations. Furthermore, two cDNAs of Ac-sps (accession no. GQ996582)
      and Ac-ni (accession no. GQ996581) were first isolated from pineapple fruits
      utilizing conserved amino-acid sequences. Homology alignment reveals that the
      amino acid sequences contain some conserved function domains. Transcription
      expression analysis of Ac-sps, Ac-susy and Ac-ni also indicated distinct patterns
      related to sugar accumulation and composition of pineapple fruits. It suggests
      that differential expressions of multiple gene families are necessary for sugar
      metabolism in various parts and developmental stages of pineapple fruit. A cycle
      of sucrose breakdown in the cytosol of sink tissues could be mediated through
      both Ac-SuSy and Ac-NI, and Ac-NI could be involved in regulating crucial steps
      by generating sugar signals to the cells in a temporally and spatially restricted
      fashion.

PMID- 22949809
TI  - Effects of high glucose on vascular endothelial growth factor synthesis and
      secretion in aortic vascular smooth muscle cells from obese and lean Zucker rats.
AB  - Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin
      deficiency and insulin resistance: in both conditions, hyperglycaemia is
      accompanied by an increased cardiovascular risk, due to increased atherosclerotic
      plaque formation/instabilization and impaired collateral vessel formation. An
      important factor in these phenomena is the Vascular Endothelial Growth Factor
      (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed
      at evaluating the role of high glucose on VEGF-A(164) synthesis and secretion in
      VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and
      OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with d-glucose
      (5.5, 15 and 25 mM) or with the osmotic controls l-glucose and mannitol, we
      measured VEGF-A(164) synthesis (western, blotting) and secretion (western
      blotting and ELISA). We observed that: (i) d-glucose dose-dependently increases
      VEGF-A(164) synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p =
      0.002-0.0001); (ii) all the effects of 15 and 25 mM d-glucose are attenuated in
      VSMC from OZR vs. LZR (p = 0.0001); (iii) l-glucose and mannitol reproduce the
      VEGF-A(164) modulation induced by d-glucose in VSMC from both LZR and OZR. Thus,
      glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC,
      an effect attenuated in the presence of insulin resistance.

PMID- 22949811
TI  - Thermal studies of Zn(II), Cd(II) and Hg(II) complexes of some N-alkyl-N-phenyl
      dithiocarbamates.
AB  - The thermal decomposition of Zn(II), Cd(II) and Hg(II) complexes of N-ethyl-N
      phenyl and N-butyl-N-phenyl dithiocarbamates have been studied using
      thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The
      products of the decomposition, at two different temperatures, were further
      characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray
      spectroscopy (EDX). The results show that while the zinc and cadmium complexes
      undergo decomposition to form metal sulphides, and further undergo oxidation
      forming metal oxides as final products, the mercury complexes gave unstable
      volatiles as the final product.

PMID- 22949810
TI  - Detection of differential levels of proteins in the urine of patients with
      endometrial cancer: analysis using two-dimensional gel electrophoresis and o
      glycan binding lectin.
AB  - Cancers can cause some proteins to be aberrantly excreted or released in the
      urine, which can be used as biomarkers. To screen for potential biomarkers for
      endometrial cancer (ECa), the urinary proteins from patients who were newly
      diagnosed with early stage ECa and untreated controls were separated using two
      dimensional gel electrophoresis (2-DE) and followed by image analysis. The
      altered levels of zinc alpha-2 glycoprotein, alpha 1-acid glycoprotein, and CD59
      were detected in the patients compared to the controls. In addition, the urine of
      the ECa patients was also found to contain relatively lower levels of a fragment
      of nebulin when the 2-DE separated urinary proteins were probed using champedak
      galactose binding (CGB) lectin. The different levels of the nebulin fragment were
      further validated by subjecting the urinary protein samples to CGB lectin
      affinity chromatography and analysis of the bound fractions by LC-MS/MS. Our data
      is suggestive of the potential use of the differentially expressed urinary
      proteins as biomarkers for ECa although this requires further extensive
      validation on clinically representative populations.

PMID- 22949812
TI  - Correlation between protein sequence similarity and crystallization reagents in
      the biological macromolecule crystallization database.
AB  - The protein structural entries grew far slower than the sequence entries. This is
      partly due to the bottleneck in obtaining diffraction quality protein crystals
      for structural determination using X-ray crystallography. The first step to
      achieve protein crystallization is to find out suitable chemical reagents.
      However, it is not an easy task. Exhausting trial and error tests of numerous
      combinations of different reagents mixed with the protein solution are usually
      necessary to screen out the pursuing crystallization conditions. Therefore, any
      attempts to help find suitable reagents for protein crystallization are helpful.
      In this paper, an analysis of the relationship between the protein sequence
      similarity and the crystallization reagents according to the information from the
      existing databases is presented. We extracted information of reagents and
      sequences from the Biological Macromolecule Crystallization Database (BMCD) and
      the Protein Data Bank (PDB) database, classified the proteins into different
      clusters according to the sequence similarity, and statistically analyzed the
      relationship between the sequence similarity and the crystallization reagents.
      The results showed that there is a pronounced positive correlation between them.
      Therefore, according to the correlation, prediction of feasible chemical reagents
      that are suitable to be used in crystallization screens for a specific protein is
      possible.

PMID- 22949813
TI  - Isolation and characterization of microsatellite markers in brown planthopper
      (Nilaparvata lugens Stal).
AB  - Brown planthopper (Nilaparvata lugens Stal) (Homoptera: Delphacidae) is an
      economically important pest on rice. In this study, 30 polymorphic microsatellite
      markers were developed from N. lugens genomic libraries using the method of Fast
      Isolation by AFLP of Sequence Containing Repeats (FIASCO). Polymorphism of each
      locus was detected in 48 individuals from two natural populations. These
      microsatellite loci revealed 2 to 18 alleles, and the expected and observed
      heterozygosities ranged from 0.042 to 0.937 and from 0.042 to 0.958,
      respectively. These markers will be useful for the future study of this
      agricultural pest in population genetics and molecular genetics.

PMID- 22949814
TI  - Isolation and characterization of 46 novel polymorphic EST-simple sequence
      repeats (SSR) markers in two Sinipercine Fishes (Siniperca) and cross-species
      amplification.
AB  - With the development of next generation sequencing technologies, transcriptome
      level sequence collections are emerging as prominent resources for the discovery
      of gene-based molecular markers. In this study, we described the isolation and
      characterization of 46 novel polymorphic microsatellite loci for Siniperca
      chuatsi and Siniperca scherzeri from the transcriptome of their F(1) interspecies
      hybrids. Forty-three of these loci were polymorphic in S. chuatsi, and 20 were
      polymorphic in S. scherzeri. In S. chuatsi, the number of alleles per locus
      ranged from 2 to 8, and the observed and expected heterozygosities varied from
      0.13 to 1.00 and from 0.33 to 0.85, respectively. In S. scherzeri, the number of
      alleles per locus ranged from 3 to 9, and the observed and expected
      heterozygosities varied from 0.19 to 1.00 and from 0.28 to 0.88, respectively. We
      also evaluated the cross-amplification of 46 polymorphic loci in four species of
      sinipercine fishes: Siniperca kneri, Siniperca undulata, Siniperca obscura, and
      Coreoperca whiteheadi. The interspecies cross-amplification rate was very high,
      totaling 94% of the 184 locus/taxon combinations tested. These markers will be a
      valuable resource for population genetic studies in sinipercine fishes.

PMID- 22949816
TI  - Molecular dynamics simulation of palmitate ester self-assembly with diclofenac.
AB  - Palm oil-based esters (POEs) are unsaturated and non-ionic esters with a great
      potential to act as chemical penetration enhancers and drug carriers for
      transdermal drug nano-delivery. A ratio of palmitate ester and nonionic Tween80
      with and without diclofenac acid was chosen from an experimentally determined
      phase diagram. Molecular dynamics simulations were performed for selected
      compositions over a period of 15 ns. Both micelles showed a prolate-like shape,
      while adding the drug produced a more compact micellar structure. Our results
      proposed that the drug could behave as a co-surfactant in our simulated model.

PMID- 22949815
TI  - Implication of tumor microenvironment in chemoresistance: tumor-associated
      stromal cells protect tumor cells from cell death.
AB  - Tumor development principally occurs following the accumulation of genetic and
      epigenetic alterations in tumor cells. These changes pave the way for the
      transformation of chemosensitive cells to chemoresistant ones by influencing the
      uptake, metabolism, or export of drugs at the cellular level. Numerous reports
      have revealed the complexity of tumors and their microenvironment with tumor
      cells located within a heterogeneous population of stromal cells. These stromal
      cells (fibroblasts, endothelial or mesothelial cells, adipocytes or adipose
      tissue-derived stromal cells, immune cells and bone marrow-derived stem cells)
      could be involved in the chemoresistance that is acquired by tumor cells via
      several mechanisms: (i) cell-cell and cell-matrix interactions influencing the
      cancer cell sensitivity to apoptosis; (ii) local release of soluble factors
      promoting survival and tumor growth (crosstalk between stromal and tumor cells);
      (iii) direct cell-cell interactions with tumor cells (crosstalk or oncologic
      trogocytosis); (iv) generation of specific niches within the tumor
      microenvironment that facilitate the acquisition of drug resistance; or (v)
      conversion of the cancer cells to cancer-initiating cells or cancer stem cells.
      This review will focus on the implication of each member of the heterogeneous
      population of stromal cells in conferring resistance to cytotoxins and
      physiological mediators of cell death.

PMID- 22949817
TI  - Comparative studies on the induction of Trichoderma harzianum mutanase by alpha
      (1->3)-glucan-rich fruiting bodies and mycelia of Laetiporus sulphureus.
AB  - Mutanase (alpha-(1->3)-glucanase) is a little-known inductive enzyme that is
      potentially useful in dentistry. Here, it was shown that the cell wall
      preparation (CWP) obtained from the fruiting body or vegetative mycelium of
      polypore fungus Laetiporus sulphureus is rich in alpha-(1->3)-glucan and can be
      successfully used for mutanase induction in Trichoderma harzianum. The content of
      this biopolymer in the CWP depended on the age of fruiting bodies and increased
      along with their maturation. In the case of CWP prepared from vegetative mycelia,
      the amount of alpha-(1->3)-glucan depended on the mycelium age and also on the
      kind of medium used for its cultivation. All CWPs prepared from the individually
      harvested fruiting body specimens induced high mutanase activity (0.53-0.82 U/mL)
      in T. harzianum after 3 days of cultivation. As for the CWPs obtained from the
      hyphal mycelia of L. sulpureus, the maximal enzyme productivity (0.34 U/mL after
      3 days of incubation) was recorded for CWP prepared from the 3 week-old mycelium
      cultivated in Sabouraud medium. Statistically, a high positive correlation was
      found between the total percentage content of alpha-(1->3)-glucan in the CWP and
      the mutanase activity.

PMID- 22949818
TI  - Evaluation of sex-specific gene expression in archived dried blood spots (DBS).
AB  - Screening newborns for treatable serious conditions is mandated in all US states
      and many other countries. After screening, Guthrie cards with residual blood
      (whole spots or portions of spots) are typically stored at ambient temperature in
      many facilities. The potential of archived dried blood spots (DBS) for at-birth
      molecular studies in epidemiological and clinical research is substantial.
      However, it is also challenging as analytes from DBS may be degraded due to
      preparation and storage conditions. We previously reported an improved assay for
      obtaining global RNA gene expression from blood spots. Here, we evaluated sex
      specific gene expression and its preservation in DBS using oligonucleotide
      microarray technology. We found X inactivation-specific transcript (XIST), lysine
      specific demethylase 5D (KDM5D) (also known as selected cDNA on Y, homolog of
      mouse (SMCY)), uncharacterized LOC729444 (LOC729444), and testis-specific
      transcript, Y-linked 21 (TTTY21) to be differentially-expressed by sex of the
      newborn. Our finding that trait-specific RNA gene expression is preserved in
      unfrozen DBS, demonstrates the technical feasibility of performing molecular
      genetic profiling using such samples. With millions of DBS potentially available
      for research, we see new opportunities in using newborn molecular gene expression
      to better understand molecular pathogenesis of perinatal diseases.

PMID- 22949819
TI  - Isolation and identification of fourteen microsatellite markers in Clivia miniata
      and Clivia nobilis (Amaryllidaceae).
AB  - Clivia is a genus of great horticultural importance and has been widely
      cultivated as ornamental plants in all over the world. In order to assess the
      phylogenetic relationships and genetic diversity of the wild Clivia species and
      cultivars, we isolated AC-enriched repeats using FIASCO from a single clone each
      of C. miniata Regel. and Clivia nobilis Lindl. Of the fourteen repeats, 10 were
      polymorphic and 4 were monomorphic. The polymorphic marker loci were
      characterized using 61 Clivia accessions. The number of alleles ranged from two
      to six, observed heterozygosity ranged from 0.04 to 1.00 and expected
      heterozygosity ranged from 0.04 to 0.83. These microsatellite marker loci provide
      tools for future studies of Clivia species and cultivars.

PMID- 22949820
TI  - Metal-sulfate induced generation of ROS in human brain cells: detection using an
      isomeric mixture of 5- and 6-carboxy-2',7'-dichlorofluorescein diacetate (carboxy
      DCFDA) as a cell permeant tracer.
AB  - Evolution of reactive oxygen species (ROS), generated during the patho
      physiological stress of nervous tissue, has been implicated in the etiology of
      several progressive human neurological disorders including Alzheimer's disease
      (AD) and amylotrophic lateral sclerosis (ALS). In this brief communication we
      used mixed isomers of 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate
      (carboxy-DCFDA; C(25)H(14)C(l2)O(9); MW 529.3), a novel fluorescent indicator, to
      assess ROS generation within human neuronal-glial (HNG) cells in primary co
      culture. We introduced pathological stress using the sulfates of 12
      environmentally-, industrially- and agriculturally-relevant divalent and
      trivalent metals including Al, Cd, Cu, Fe, Hg, Ga, Mg, Mn, Ni, Pb, Sn and Zn. In
      this experimental test system, of all the metal sulfates analyzed, aluminum
      sulfate showed by far the greatest ability to induce intracellular ROS. These
      studies indicate the utility of using isomeric mixtures of carboxy-H(2)DCFDA
      diacetates as novel and highly sensitive, long-lasting, cell-permeant,
      fluorescein-based tracers for quantifying ROS generation in intact, metabolizing
      human brain cells, and in analyzing the potential epigenetic contribution of
      different metal sulfates to ROS-generation and ROS-mediated neurological
      dysfunction.

PMID- 22949821
TI  - Arsenic trioxide inhibits cell growth and induces apoptosis through inactivation
      of notch signaling pathway in breast cancer.
AB  - Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic
      cell death in many human cancer cells including breast cancer. However, the
      precise molecular mechanisms underlying the anti-tumor activity of arsenic
      trioxide are still largely unknown. In the present study, we assessed the effects
      of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For
      mechanistic studies, we used multiple cellular and molecular approaches such as
      MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting,
      and invasion assays. For the first time, we found a significant reduction in cell
      viability in arsenic trioxide-treated cells in a dose-dependent manner, which was
      consistent with induction of apoptosis and also associated with down-regulation
      of Notch-1 and its target genes. Taken together, our findings provide evidence
      showing that the down-regulation of Notch-1 by arsenic trioxide could be an
      effective approach, to cause down-regulation of Bcl-2, and NF-kappaB, resulting
      in the inhibition of cell growth and invasion as well as induction of apoptosis.
      These results suggest that the anti-tumor activity of arsenic trioxide is in part
      mediated through a novel mechanism involving inactivation of Notch-1 and its
      target genes. We also suggest that arsenic trioxide could be further developed as
      a potential therapeutic agent for the treatment of breast cancer.

PMID- 22949822
TI  - Neuroprotective effects of triterpene glycosides from glycine max against
      glutamate induced toxicity in primary cultured rat cortical cells.
AB  - To examine the neuroprotective effects of Glycine max, we tested its protection
      against the glutamate-induced toxicity in primary cortical cultured neurons. In
      order to clarify the neuroprotective mechanism(s) of this observed effect,
      isolation was performed to seek and identify active fractions and components.
      From such fractionation, two triterpene glycosides, 3-O-[alpha-l
      rhamnopyranosyl(1-2)-beta-d-glucopyranosyl(1-2)-beta-d-glucuronopyranosyl]olean
      12-en-3beta,22beta,24-triol (1) and 3-O-[beta-d-glucopyranosyl(1-2)-beta-d
      galactopyranosyl(1-2)-beta-d-glucuronopyranosyl]olean-12-en-3beta,22beta,24-triol
      (2) were isolated with the methanol extracts with of air-dried Glycine max. Among
      these compounds, compound 2 exhibited significant neuroprotective activities
      against glutamate-induced toxicity, exhibiting cell viability of about 50% at
      concentrations ranging from 0.1 MUM to 10 MUM. Therefore, the neuroprotective
      effect of Glycine max might be due to the inhibition of glutamate-induced
      toxicity by triterpene glycosides.

PMID- 22949824
TI  - Enzymatic properties and mutational studies of chalcone synthase from
      Physcomitrella patens.
AB  - PpCHS is a member of the type III polyketide synthase family and catalyses the
      synthesis of the flavonoid precursor naringenin chalcone from p-coumaroyl-CoA.
      Recent research reports the production of pyrone derivatives using either
      hexanoyl-CoA or butyryl-CoA as starter molecule. The Cys-His-Asn catalytic triad
      found in other plant chalcone synthase predicted polypeptides is conserved in
      PpCHS. Site directed mutagenesis involving these amino acids residing in the
      active-site cavity revealed that the cavity volume of the active-site plays a
      significant role in the selection of starter molecules as well as product
      formation. Substitutions of Cys 170 with Arg and Ser amino acids decreased the
      ability of the PpCHS to utilize hexanoyl-CoA as a starter molecule, which
      directly effected the production of pyrone derivatives (products). These
      substitutions are believed to have a restricted number of elongations of the
      growing polypeptide chain due to the smaller cavity volume of the mutant's active
      site.

PMID- 22949823
TI  - Selenium compounds, apoptosis and other types of cell death: an overview for
      cancer therapy.
AB  - Selenium (Se) is an essential trace element involved in different physiological
      functions of the human body and plays a role in cancer prevention and treatment.
      Induction of apoptosis is considered an important cellular event that can account
      for the cancer preventive effects of Se. The mechanisms of Se-induced apoptosis
      are associated with the chemical forms of Se and their metabolism as well as the
      type of cancer studied. So, some selenocompounds, such as SeO(2) involve the
      activation of caspase-3 while sodium selenite induces apoptosis in the absence of
      the activation of caspases. Modulation of mitochondrial functions has been
      reported to play a key role in the regulation of apoptosis and also to be one of
      the targets of Se compounds. Other mechanisms for apoptosis induction are the
      modulation of glutathione and reactive oxygen species levels, which may function
      as intracellular messengers to regulate signaling pathways, or the regulation of
      kinase, among others. Emerging evidence indicates the overlaps between the
      apoptosis and other types of cell death such as autophagy. In this review we
      report different processes of cell death induced by Se compounds in cancer
      treatment and prevention.

PMID- 22949825
TI  - Neuroprotective effects of germinated brown rice against hydrogen peroxide
      induced cell death in human SH-SY5Y cells.
AB  - The neuroprotective and antioxidative effects of germinated brown rice (GBR),
      brown rice (BR) and commercially available gamma-aminobutyric acid (GABA) against
      cell death induced by hydrogen peroxide (H(2)O(2)) in human neuroblastoma SH-SY5Y
      cells have been investigated. Results show that GBR suppressed H(2)O(2)-mediated
      cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells.
      Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented
      phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of
      apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and
      antioxidative activities as compared to BR and GABA. These results indicate that
      GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y
      cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore,
      GBR could be developed as a value added functional food to prevent
      neurodegenerative diseases caused by oxidative stress and apoptosis.

PMID- 22949827
TI  - Effects of cyclooxygenase inhibitors in combination with taxol on expression of
      cyclin D1 and Ki-67 in a xenograft model of ovarian carcinoma.
AB  - The present study was designed to investigate the effects of cyclooxygenase (COX)
      inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in
      human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were
      treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone, 3 mg/kg SC
      560 (a COX-1 selective inhibitor) alone by gavage twice a day, 20 mg/kg taxol
      alone by intraperitoneally (i.p.) once a week, or celecoxib/taxol, SC
      560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test
      the mechanism of the combination treatment, the index of cell proliferation and
      expression of cyclin D1 in tumor tissues were determined by immunohistochemistry.
      The mean tumor volume in the treated groups was significantly lower than control
      (p < 0.05), and in the three-drug combination group, tumor volume was reduced by
      58.27% (p < 0.01); downregulated cell proliferation and cyclin D1 expression were
      statistically significant compared with those of the control group (both p <
      0.01). This study suggests that the effects of COX selective inhibitors on the
      growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse
      xenograft model were similar to taxol. The three-drug combination showing a
      better decreasing tendency in growth-inhibitory effect during the experiment may
      have been caused by suppressing cyclin D1 expression.

PMID- 22949826
TI  - Molecular dynamic simulation insights into the normal state and restoration of
      p53 function.
AB  - As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in
      cancer prevention. Almost 50 percent of all human malignant tumors are closely
      related to a deletion or mutation in p53. The activity of p53 is inhibited by
      over-active celluar antagonists, especially by the over-expression of the
      negative regulators MDM2 and MDMX. Protein-protein interactions, or post
      translational modifications of the C-terminal negative regulatory domain of p53,
      also regulate its tumor suppressor activity. Restoration of p53 function through
      peptide and small molecular inhibitors has become a promising strategy for novel
      anti-cancer drug design and development. Molecular dynamics simulations have been
      extensively applied to investigate the conformation changes of p53 induced by
      protein-protein interactions and protein-ligand interactions, including peptide
      and small molecular inhibitors. This review focuses on the latest MD simulation
      research, to provide an overview of the current understanding of interactions
      between p53 and its partners at an atomic level.

PMID- 22949828
TI  - Constituents from Vigna vexillata and their anti-inflammatory activity.
AB  - The seeds of Vigna genus are important food resources and there have already been
      many reports regarding their bioactivities. In our preliminary bioassay, the
      chloroform layer of methanol extracts of V. vexillata demonstrated significant
      anti-inflammatory bioactivity. Therefore, the present research is aimed to purify
      and identify the anti-inflammatory principles of V. vexillata. One new sterol (1)
      and two new isoflavones (2,3) were reported from the natural sources for the
      first time and their chemical structures were determined by the spectroscopic and
      mass spectrometric analyses. In addition, 37 known compounds were identified by
      comparison of their physical and spectroscopic data with those reported in the
      literature. Among the isolates, daidzein (23), abscisic acid (25), and quercetin
      (40) displayed the most significant inhibition of superoxide anion generation and
      elastase release.

PMID- 22949829
TI  - Structural and catalytic differences between two FADH(2)-dependent
      monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100
      and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134.
AB  - 2,4,5-TCP 4-monooxygenase (TftD) and 2,4,6-TCP 4-monooxygenase (TcpA) have been
      discovered in the biodegradation of 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6
      trichlorophenol (2,4,6-TCP). TcpA and TftD belong to the reduced flavin adenine
      dinucleotide (FADH(2))-dependent monooxygenases and both use 2,4,6-TCP as a
      substrate; however, the two enzymes produce different end products. TftD
      catalyzes a typical monooxygenase reaction, while TcpA catalyzes a typical
      monooxygenase reaction followed by a hydrolytic dechlorination. We have
      previously reported the 3D structure of TftD and confirmed the catalytic residue,
      His289. Here we have determined the crystal structure of TcpA and investigated
      the apparent differences in specificity and catalysis between these two closely
      related monooxygenases through structural comparison. Our computational docking
      results suggest that Ala293 in TcpA (Ile292 in TftD) is possibly responsible for
      the differences in substrate specificity between the two monooxygenases. We have
      also identified that Arg101 in TcpA could provide inductive effects/charge
      stabilization during hydrolytic dechlorination. The collective information
      provides a fundamental understanding of the catalytic reaction mechanism and the
      parameters for substrate specificity. The information may provide guidance for
      designing bioremediation strategies for polychlorophenols, a major group of
      environmental pollutants.

PMID- 22949830
TI  - The metalloporphyrin antioxidant, MnTE-2-PyP, inhibits Th2 cell immune responses
      in an asthma model.
AB  - MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway
      inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we
      hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone
      marrow derived dendritic cells (DC) and OVA(323-339)-specific Th2 cells were
      cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to
      the co-culturing of the two cell types in the presence of an OVA(323-339) peptide
      and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL
      4, IL-5 and IFNgamma production and inhibited Th2 cell proliferation in the DC
      Th2 co-culturing system in the presence of the OVA(323-339) peptide. Similar
      results were obtained using the CD3/CD28 cell-activation system; the addition of
      MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25
      expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit
      the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory
      molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major
      mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC
      and suppressing Th2 cell proliferation and activation.

PMID- 22949831
TI  - High throughput mining and characterization of microsatellites from common carp
      genome.
AB  - In order to supply sufficient microsatellite loci for high-density linkage
      mapping, whole genome shotgun (WGS) sequences of the common carp (Cyprinus
      carpio) were assembled and surveyed for microsatellite identification. A total of
      79,014 microsatellites were collected which were harbored in 68,827 distinct
      contig sequences. These microsatellites were characterized in the common carp
      genome. Information of all microsatellites, including previously published BAC
      based microsatellites, was then stored in a MySQL database, and a web-based
      database interface (http://genomics.cafs.ac.cn/ssrdb) was built for public access
      and download. A total of 3,110 microsatellites, including 1,845 from WGS and
      1,265 from BAC end sequences (BES), were tested and genotyped on a mapping family
      with 192 individuals. A total of 963 microsatellites markers were validated with
      polymorphism in the mapping family. They will soon be used for high-density
      linkage mapping with a vast number of polymorphic SNP markers.

PMID- 22949832
TI  - Less expression of prohibitin is associated with increased paired box 2 (PAX2) in
      renal interstitial fibrosis rats.
AB  - Prohibitin (PHB) and paired box 2 (PAX2) are associated with the development of
      renal interstitial fibrosis (RIF). This study was performed to investigate
      whether or not the PHB could regulate the PAX2 gene expression in unilateral
      ureteral obstruction (UUO) in rats. Eighty Wistar male rats were randomly divided
      into two groups: sham operation group (SHO) and model group subjected to
      unilateral ureteral obstruction (GU), n = 40, respectively. The model was
      established by left ureteral ligation. Renal tissues were collected at 14-day and
      28-day after surgery. RIF index, protein expression of PHB, PAX2, transforming
      growth factor-betal (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), collagen
      IV (Col-IV), fibronectin (FN) or cleaved Caspase-3, and cell apoptosis index in
      renal interstitium, and mRNA expressions of PHB, PAX2 and TGF-beta1 in renal
      tissue were detected. When compared with those in SHO group, expression of PHB
      (mRNA and protein) was significantly reduced, and expressions of PAX2 and TGF
      beta1 (protein and mRNA) were markedly increased in the GU group (each p < 0.01).
      Protein expressions of alpha-SMA, Col-IV, FN and cleaved Caspase-3, and RIF index
      or cell apoptosis index in the GU group were markedly increased when compared
      with those in the SHO group (each p < 0.01). The protein expression of PHB was
      negatively correlated with protein expression of PAX2, TGF-beta1, alpha-SMA, Col
      IV, FN or cleaved Caspase-3, and RIF index or cell apoptosis index (all p <
      0.01). In conclusion, less expression of PHB is associated with increased PAX2
      gene expression and RIF index in UUO rats, suggesting that increasing the PHB
      expression is a potential therapeutic target for prevention of RIF.

PMID- 22949834
TI  - Conformational solvation studies of LIGNOLs with molecular dynamics and conductor
      like screening model.
AB  - Molecular dynamics (MD) simulations were performed on sterically hindered alpha
      conidendrin-based chiral 1,4-diols (LIGNOLs) from the naturally occurring lignan
      hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was
      to explore the conformational behaviour of the LIGNOLs in aqueous solution
      adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually
      and they were modeled with the OPLS-AA force field implemented in GROMACS. The
      four most relevant torsional angles in the LIGNOLs were properly analyzed during
      the simulations. The determining property for the conformation preferred in
      aqueous solution was found to be the lowest energy in gas phase. The solvation
      effects on the LIGNOLs were also studied by quantum chemical calculations
      applying the COnductor-like Screening MOdel (COSMO). The hydration studies of the
      MD simulations showed that several of these LIGNOLs, produced from a renewable
      source, have a great potential of acting as chiral catalysts.

PMID- 22949833
TI  - Molecular mechanisms of aging and immune system regulation in Drosophila.
AB  - Aging is a complex process that involves the accumulation of deleterious changes
      resulting in overall decline in several vital functions, leading to the
      progressive deterioration in physiological condition of the organism and
      eventually causing disease and death. The immune system is the most important
      host-defense mechanism in humans and is also highly conserved in insects.
      Extensive research in vertebrates has concluded that aging of the immune function
      results in increased susceptibility to infectious disease and chronic
      inflammation. Over the years, interest has grown in studying the molecular
      interaction between aging and the immune response to pathogenic infections. The
      fruit fly Drosophila melanogaster is an excellent model system for dissecting the
      genetic and genomic basis of important biological processes, such as aging and
      the innate immune system, and deciphering parallel mechanisms in vertebrate
      animals. Here, we review the recent advances in the identification of key players
      modulating the relationship between molecular aging networks and immune signal
      transduction pathways in the fly. Understanding the details of the molecular
      events involved in aging and immune system regulation will potentially lead to
      the development of strategies for decreasing the impact of age-related diseases,
      thus improving human health and life span.

PMID- 22949835
TI  - Acute effect of Ghrelin on ischemia/reperfusion injury in the rat spinal cord.
AB  - Ghrelin, a 28-amino acid peptide, is mainly secreted by the stomach. Ghrelin has
      been shown to have neuroprotective effects. However, whether ghrelin protects the
      spinal cord from ischemia/reperfusion (I/R) injury is unknown. To investigate
      this, 60 rats were randomly divided into three different groups: the sham group
      (n = 20), the vehicle group (n = 20), and the Ghrelin group (100 MUg/kg, n = 20).
      Rats were sacrificed 12, 24, 48 and 72 h after ischemia. After the evaluation of
      neurologic function (48 h), the spinal cords were immediately removed for the
      determination of myeloperoxidase (MPO) activity (12-72 h). Apoptosis was
      quantitatively measured using the terminal transferase UTP nick end-labeling
      (TUNEL) method (24 h). The expression of bax and bcl-2 were evaluated by Western
      blot analysis (1 h), and GHSR-1a mRNA expression was detected using reverse
      transcriptase polymerase chain reaction (24 h). The neurological motor function
      was evaluated by 'Tarlov's score'. The neurologic outcomes in the ghrelin-group
      were significantly better than those in the vehicle group (p < 0.05). Serum tumor
      necrosis factor (TNF-alpha) levels were assessed in the peripheral venous blood.
      Ghrelin decreased the serum TNF-alpha levels and ameliorated the down regulation
      of spinal cord MPO activity. The expression of ghrelin receptors (GHSR-1a) in the
      rat spinal cord was decreased by I/R injury and increased by ghrelin. Ghrelin
      reduced the TUNEL-positive rate. Greater bcl-2, HSP27, HSP70, and attenuated bax
      expression were observed in the ghrelin-treated rats. Our results suggest that
      ghrelin administration may inhibit spinal I/R injury. Moreover, the improvement
      of neurologic function in rats was increased after the ghrelin treatment.

PMID- 22949836
TI  - Wogonin induces reactive oxygen species production and cell apoptosis in human
      glioma cancer cells.
AB  - Glioma is the most common primary adult brain tumor with poor prognosis because
      of the ease of spreading tumor cells to other regions of the brain. Cell
      apoptosis is frequently targeted for developing anti-cancer drugs. In the present
      study, we have assessed wogonin, a flavonoid compound isolated from Scutellaria
      baicalensis Georgi, induced ROS generation, endoplasmic reticulum (ER) stress and
      cell apoptosis. Wogonin induced cell death in two different human glioma cells,
      such as U251 and U87 cells but not in human primary astrocytes (IC 50 > 100 MUM).
      Wogonin-induced apoptotic cell death in glioma cells was measured by propidine
      iodine (PI) analysis, Tunnel assay and Annexin V staining methods. Furthermore,
      wogonin also induced caspase-9 and caspase-3 activation as well as up-regulation
      of cleaved PARP expression. Moreover, treatment of wogonin also increased a
      number of signature ER stress markers glucose-regulated protein (GRP)-78, GRP-94,
      Calpain I, and phosphorylation of eukaryotic initiation factor-2alpha
      (eIF2alpha). Treatment of human glioma cells with wogonin was found to induce
      reactive oxygen species (ROS) generation. Wogonin induced ER stress-related
      protein expression and cell apoptosis was reduced by the ROS inhibitors apocynin
      and NAC (N-acetylcysteine). The present study provides evidence to support the
      fact that wogonin induces human glioma cell apoptosis mediated ROS generation, ER
      stress activation and cell apoptosis.

PMID- 22949837
TI  - Development of microsatellite markers using pyrosequencing in Galium trifidum
      (Rubiaceae), a rare species in Central Europe.
AB  - We identify a large number of microsatellites from Galium trfidum, a plant
      species considered rare and endangered in Central and Western Europe. Using a
      combination of a total enriched genomic library and small-scale 454
      pyrosequencing, we determined 9755 contigs with a length of 100 to 6192 bp.
      Within this dataset, we identified 153 SSR motifs in 144 contigs. Here, we tested
      14 microsatellite loci in 2 populations of G. trifidum. The number of alleles and
      expected heterozygosity were 1-8 (mean 3.2) and 0.00-0.876 (0.549 on average),
      respectively. The markers described in this study will be useful for evaluating
      genetic diversity within and between populations, and gene flow between G.
      trifidum populations. These markers could also be applied to investigate the
      biological aspects of G. trifidum, such as the population dynamics and clonal
      structure, and to develop effective conservation programs for the Central
      European populations of this species.

PMID- 22949838
TI  - Molecular mechanisms of epigenetic variation in plants.
AB  - Natural variation is defined as the phenotypic variation caused by spontaneous
      mutations. In general, mutations are associated with changes of nucleotide
      sequence, and many mutations in genes that can cause changes in plant development
      have been identified. Epigenetic change, which does not involve alteration to the
      nucleotide sequence, can also cause changes in gene activity by changing the
      structure of chromatin through DNA methylation or histone modifications. Now
      there is evidence based on induced or spontaneous mutants that epigenetic changes
      can cause altering plant phenotypes. Epigenetic changes have occurred frequently
      in plants, and some are heritable or metastable causing variation in epigenetic
      status within or between species. Therefore, heritable epigenetic variation as
      well as genetic variation has the potential to drive natural variation.

PMID- 22949839
TI  - Green synthesis of silver nanoparticles through reduction with Solanum
      xanthocarpum L. berry extract: characterization, antimicrobial and urease
      inhibitory activities against Helicobacter pylori.
AB  - A green synthesis route for the production of silver nanoparticles using methanol
      extract from Solanum xanthocarpum berry (SXE) is reported in the present
      investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance
      (SPR) band centered at 406 nm, were synthesized by reacting SXE (as capping as
      well as reducing agent) with AgNO(3) during a 25 min process at 45  degrees C.
      The synthesized AgNps were characterized using UV-Visible spectrophotometry,
      powdered X-ray diffraction, and transmission electron microscopy (TEM). The
      results showed that the time of reaction, temperature and volume ratio of SXE to
      AgNO(3) could accelerate the reduction rate of Ag(+) and affect the AgNps size
      and shape. The nanoparticles were found to be about 10 nm in size, mono-dispersed
      in nature, and spherical in shape. In vitro anti-Helicobacter pylori activity of
      synthesized AgNps was tested against 34 clinical isolates and two reference
      strains of Helicobacter pylori by the agar dilution method and compared with
      AgNO(3) and four standard drugs, namely amoxicillin (AMX), clarithromycin (CLA),
      metronidazole (MNZ) and tetracycline (TET), being used in anti-H. pylori therapy.
      Typical AgNps sample (S1) effectively inhibited the growth of H. pylori,
      indicating a stronger anti-H. pylori activity than that of AgNO(3) or MNZ, being
      almost equally potent to TET and less potent than AMX and CLA. AgNps under study
      were found to be equally efficient against the antibiotic-resistant and
      antibiotic-susceptible strains of H. pylori. Besides, in the H. pylori urease
      inhibitory assay, S1 also exhibited a significant inhibition. Lineweaver-Burk
      plots revealed that the mechanism of inhibition was noncompetitive.

PMID- 22949840
TI  - Methods for identification of CA125 from ovarian cancer ascites by high
      resolution mass spectrometry.
AB  - CA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory
      sensitivity and specificity especially at early stage. It is quantified by
      antibody-based immunoassays; however different molecular weight isoforms have
      been described in the literature which have never been validated by mass
      spectrometry, potentially affecting the diagnostic accuracy and clinical
      reliability of the test. In this study, CA125 was detected by Western blot and
      its identity confirmed by mass spectrometry. Two-dimensional (2D) gel
      electrophoresis in combination with mass spectrometry revealed that positive
      Western blot signals up to 500 kDa are most likely false-positive interactions of
      M11-like and OC125-like antibodies. Fibronectin, identified as one of these false
      positive interaction partners, increased the reading for CA125 in a first
      generation ELISA significantly (p = 0.02). The existence of low-molecular weight
      isoforms of CA125 is therefore questionable and is most likely reflecting cross
      reactivity of the antibodies with other proteins. This would explain the
      conflicting reports on the molecular structure of CA125 and also the
      inconsistency of CA125 levels by different ELISAs. Our results are also the first
      steps towards a mass spectrometric assay for CA125 quantification, which would
      improve sensitivity and reliability.

PMID- 22949841
TI  - Chick chorioallantoic membrane (CAM) assay as an in vivo model to study the
      effect of newly identified molecules on ovarian cancer invasion and metastasis.
AB  - The majority of ovarian cancer patients present with advanced disease and despite
      aggressive treatment, prognosis remains poor. Significant improvement in ovarian
      cancer survival will require the development of more effective molecularly
      targeted therapeutics. Commonly, mouse models are used for the in vivo assessment
      of potential new therapeutic targets in ovarian cancer. However, animal models
      are costly and time consuming. Other models, such as the chick embryo
      chorioallantoic membrane (CAM) assay, are therefore an attractive alternative.
      CAM assays have been widely used to study angiogenesis and tumor invasion of
      colorectal, prostate and brain cancers. However, there have been limited studies
      that have used CAM assays to assess ovarian cancer invasion and metastasis. We
      have therefore developed a CAM assay protocol to monitor the metastatic
      properties of ovarian cancer cells (OVCAR-3, SKOV-3 and OV-90) and to study the
      effect of potential therapeutic molecules in vivo. The results from the CAM assay
      are consistent with cancer cell motility and invasion observed in in vitro
      assays. Our results demonstrate that the CAM assay is a robust and cost effective
      model to study ovarian cancer cell metastasis. It is therefore a very useful in
      vivo model for screening of potential novel therapeutics.

PMID- 22949842
TI  - Synthesis of triptorelin lactate catalyzed by lipase in organic media.
AB  - Triptorelin lactate was successfully synthesized by porcine pancreatic lipase
      (PPL) in organic solvents. The effects of acyl donor, substrate ratio, organic
      solvent, temperature, and water activity were investigated. Under the optimum
      conditions, a yield of 30% for its ester could be achieved in the reaction for
      about 48 h.

PMID- 22949843
TI  - Combined phosphatase and tensin homolog (PTEN) loss and fatty acid synthase (FAS)
      overexpression worsens the prognosis of Chinese patients with hepatocellular
      carcinoma.
AB  - We aimed to investigate the expression pattern of phosphatase and tensin homolog
      (PTEN), to evaluate the relationship between PTEN expression and
      clinicopathological characteristics, including fatty acid synthase (FAS)
      expression, and to determine the correlations of PTEN and FAS expression with
      survival in Chinese patients with hepatocellular carcinoma (HCC). The expression
      patterns of PTEN and FAS were determined using tissue microarrays and
      immunohistochemistry. The expression of PTEN was compared with the
      clinicopathological characteristics of HCC, including FAS expression. Receiver
      operator characteristic curves were used to calculate the clinical sensitivity
      and specificity of PTEN expression. Kaplan-Meier survival curves were constructed
      to evaluate the correlations of PTEN loss and FAS overexpression with overall
      survival. We found that the loss of PTEN expression occurred predominantly in the
      cytoplasm, while FAS was mainly localized to the cytoplasm. Cytoplasmic and total
      PTEN expression levels were significantly decreased in HCC compared with adjacent
      non-neoplastic tissue (both, p < 0.0001). Decreased cytoplasmic and total PTEN
      expression showed significant clinical sensitivity and specificity for HCC (both,
      p < 0.0001). Downregulation of PTEN in HCC relative to non-neoplastic tissue was
      significantly correlated with histological grade (p = 0.043 for histological
      grades I-II versus grade III). Loss of total PTEN was significantly correlated
      with FAS overexpression (p = 0.014). Loss of PTEN was also associated with poor
      prognosis of patients with poorly differentiated HCC (p = 0.049). Moreover, loss
      of PTEN combined with FAS overexpression was associated with significantly worse
      prognosis compared with other HCC cases (p = 0.011). Our data indicate that PTEN
      may serve as a potential diagnostic and prognostic marker of HCC. Upregulating
      PTEN expression and inhibiting FAS expression may offer a novel therapeutic
      approach for HCC.

PMID- 22949844
TI  - RNA-mediated gene silencing signals are not graft transmissible from the
      rootstock to the scion in greenhouse-grown apple plants Malus sp.
AB  - RNA silencing describes the sequence specific degradation of RNA targets.
      Silencing is a non-cell autonomous event that is graft transmissible in different
      plant species. The present study is the first report on systemic acquired dsRNA
      mediated gene silencing of transgenic and endogenous gene sequences in a woody
      plant like apple. Transgenic apple plants overexpressing a hairpin gene construct
      of the gusA reporter gene were produced. These plants were used as rootstocks and
      grafted with scions of the gusA overexpressing transgenic apple clone T355. After
      grafting, we observed a reduction of the gusA gene expression in T355 scions in
      vitro, but not in T355 scions grown in the greenhouse. Similar results were
      obtained after silencing of the endogenous Mdans gene in apple that is
      responsible for anthocyanin biosynthesis. Subsequently, we performed grafting
      experiments with Mdans silenced rootstocks and red leaf scions of TNR31-35 in
      order to evaluate graft transmitted silencing of the endogenous Mdans. The
      results obtained suggested a graft transmission of silencing signals in in vitro
      shoots. In contrast, no graft transmission of dsRNA-mediated gene silencing
      signals was detectable in greenhouse-grown plants and in plants grown in an
      insect protection tent.

PMID- 22949845
TI  - Effects of a buried cysteine-to-serine mutation on yeast triosephosphate
      isomerase structure and stability.
AB  - All the members of the triosephosphate isomerase (TIM) family possess a cystein
      residue (Cys126) located near the catalytically essential Glu165. The
      evolutionarily conserved Cys126, however, does not seem to play a significant
      role in the catalytic activity. On the other hand, substitution of this residue
      by other amino acid residues destabilizes the dimeric enzyme, especially when Cys
      is replaced by Ser. In trying to assess the origin of this destabilization we
      have determined the crystal structure of Saccharomyces cerevisiae TIM (ScTIM) at
      1.86 A resolution in the presence of PGA, which is only bound to one subunit.
      Comparisons of the wild type and mutant structures reveal that a change in the
      orientation of the Ser hydroxyl group, with respect to the Cys sulfhydryl group,
      leads to penetration of water molecules and apparent destabilization of residues
      132-138. The latter results were confirmed by means of Molecular Dynamics, which
      showed that this region, in the mutated enzyme, collapses at about 70 ns.

PMID- 22949846
TI  - Forster resonance energy transfer (FRET) correlates of altered subunit
      stoichiometry in cys-loop receptors, exemplified by nicotinic alpha4beta2.
AB  - We provide a theory for employing Forster resonance energy transfer (FRET)
      measurements to determine altered heteropentameric ion channel stoichiometries in
      intracellular compartments of living cells. We simulate FRET within nicotinic
      receptors (nAChRs) whose alpha4 and beta2 subunits contain acceptor and donor
      fluorescent protein moieties, respectively, within the cytoplasmic loops. We
      predict FRET and normalized FRET (NFRET) for the two predominant stoichiometries,
      (alpha4)(3)(beta2)(2)vs. (alpha4)(2)(beta2)(3). Studying the ratio between FRET
      or NFRET for the two stoichiometries, minimizes distortions due to various
      photophysical uncertainties. Within a range of assumptions concerning the
      distance between fluorophores, deviations from plane pentameric geometry, and
      other asymmetries, the predicted FRET and NFRET for (alpha4)(3)(beta2)(2) exceeds
      that of (alpha4)(2)(beta2)(3). The simulations account for published data on
      transfected Neuro2a cells in which alpha4beta2 stoichiometries were manipulated
      by varying fluorescent subunit cDNA ratios: NFRET decreased monotonically from
      (alpha4)(3)(beta2)(2) stoichiometry to mostly (alpha4)(2)(beta2)(3). The
      simulations also account for previous macroscopic and single-channel observations
      that pharmacological chaperoning by nicotine and cytisine increase the
      (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) populations, respectively. We
      also analyze sources of variability. NFRET-based monitoring of changes in subunit
      stoichiometry can contribute usefully to studies on Cys-loop receptors.

PMID- 22949848
TI  - 2,3-dihydro-1H-cyclopenta[b]quinoline derivatives as acetylcholinesterase
      inhibitors-synthesis, radiolabeling and biodistribution.
AB  - In the present study we describe the synthesis and biological assessment of new
      tacrine analogs in the course of inhibition of acetylcholinesterase. The obtained
      molecules were synthesized in a condensation reaction between activated 6-BOC
      hydrazinopyridine-3-carboxylic acid and 8-aminoalkyl derivatives of 2,3-dihydro
      1H-cyclopenta[b]quinoline. Activities of the newly synthesized compounds were
      estimated by means of Ellman's method. Compound 6h (IC(50) = 3.65 nM) was found
      to be most active. All obtained novel compounds present comparable activity to
      that of tacrine towards acetylcholinesterase (AChE) and, simultaneously, lower
      activity towards butyrylcholinesterase (BChE). Apart from 6a, all synthesized
      compounds are characterized by a higher affinity for AChE and a lower affinity
      for BChE in comparison with tacrine. Among all obtained molecules, compound 6h
      presented the highest selectivity towards inhibition of acetylcholinesterase.
      Molecular modeling showed that all compounds demonstrated a similar binding mode
      with AChE and interacted with catalytic and peripheral sites of AChE. Also, a
      biodistribution study of compound 6a radiolabeled with (99m)Tc was performed.

PMID- 22949849
TI  - New biofuel integrating glycerol into its composition through the use of covalent
      immobilized pig pancreatic lipase.
AB  - By using 1,3-specific Pig Pancreatic lipase (EC 3.1.1.3 or PPL), covalently
      immobilized on AlPO(4)/Sepiolite support as biocatalyst, a new second-generation
      biodiesel was obtained in the transesterification reaction of sunflower oil with
      ethanol and other alcohols of low molecular weight. The resulting biofuel is
      composed of fatty acid ethyl esters and monoglycerides (FAEE/MG) blended in a
      molar relation 2/1. This novel product, which integrates glycerol as
      monoacylglycerols (MG) into the biofuel composition, has similar physicochemical
      properties compared to those of conventional biodiesel and also avoids the
      removal step of this by-product. The biocatalyst was found to be strongly fixed
      to the inorganic support (75%). Nevertheless, the efficiency of the immobilized
      enzyme was reduced to half (49.1%) compared to that of the free PPL. The
      immobilized enzyme showed a remarkable stability as well as a great reusability
      (more than 40 successive reuses) without a significant loss of its initial
      catalytic activity. Immobilized and free enzymes exhibited different reaction
      mechanisms, according to the different results in the Arrhenius parameters (Ln A
      and Ea). However, the use of supported PPL was found to be very suitable for the
      repetitive production of biofuel due to its facile recyclability from the
      reaction mixture.

PMID- 22949847
TI  - Blood glutamate scavenging: insight into neuroprotection.
AB  - Brain insults are characterized by a multitude of complex processes, of which
      glutamate release plays a major role. Deleterious excess of glutamate in the
      brain's extracellular fluids stimulates glutamate receptors, which in turn lead
      to cell swelling, apoptosis, and neuronal death. These exacerbate neurological
      outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate
      receptors have failed to demonstrate clinical benefit. Alternatively, eliminating
      excess glutamate from brain interstitial fluids by making use of the naturally
      occurring brain-to-blood glutamate efflux has been shown to be effective in
      various animal studies. This is facilitated by gradient driven transport across
      brain capillary endothelial glutamate transporters. Blood glutamate scavengers
      enhance this naturally occurring mechanism by reducing the blood glutamate
      concentration, thus increasing the rate at which excess glutamate is cleared.
      Blood glutamate scavenging is achieved by several mechanisms including:
      catalyzation of the enzymatic process involved in glutamate metabolism,
      redistribution of glutamate into tissue, and acute stress response. Regardless of
      the mechanism involved, decreased blood glutamate concentration is associated
      with improved neurological outcome. This review focuses on the physiological,
      mechanistic and clinical roles of blood glutamate scavenging, particularly in the
      context of acute and chronic CNS injury. We discuss the details of brain-to-blood
      glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and
      exogenous blood glutamate scavenging systems, and redistribution of glutamate. We
      then propose different applied methodologies to reduce blood and brain glutamate
      concentrations and discuss the neuroprotective role of blood glutamate
      scavenging.

PMID- 22949850
TI  - Quantitative expression of C-type lectin receptors in humans and mice.
AB  - C-type lectin receptors and their adaptor molecules are involved in the
      recognition of glycosylated self-antigens and pathogens. However, little is known
      about the species- and organ-specific expression profiles of these molecules. We
      therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN,
      Syk, Card-9, Bcl-10, Malt-1, Src, Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12
      in 11 solid organs of human and mice. Mouse organs revealed lower mRNA levels of
      most molecules compared to spleen. However, Dec-205 and Galectin-1 in thymus, Src
      in brain, MR2, Card-9, Bcl-10, Src, and Dec-205 in small intestine, MR2, Bcl-10,
      Src, Galectin-1 in kidney, and Src and Galectin-1 in muscle were at least 2-fold
      higher expressed compared to spleen. Human lung, liver and heart expressed higher
      mRNA levels of most genes compared to spleen. Dectin-1, MR1, Syk and Trem-1 mRNA
      were strongly up-regulated upon ischemia-reperfusion injury in murine kidney.
      Tim3, DAP-12, Card-9, DC-SIGN and MR2 were further up-regulated during renal
      fibrosis. Murine kidney showed higher DAP-12, Syk, Card-9 and Dectin-1 mRNA
      expression during the progression of lupus nephritis. Thus, the organ-, and
      species-specific expression of C-type lectin receptors is different between mice
      and humans which must be considered in the interpretation of related studies.

PMID- 22949851
TI  - Cyclodextrin-based [1]rotaxanes on gold nanoparticles.
AB  - Transformation of mechanically interlocked molecules (e.g., rotaxanes and
      catenanes) into nanoscale materials or devices is an important step towards their
      real applications. In our current work, an azobenzene-modified beta-cyclodextrin
      (beta-CD) derivative that can form a self-inclusion complex in aqueous solution
      was prepared. The self-included beta-CD derivative was then functionalized onto a
      gold nanoparticle (AuNP) surface via a ligand-exchange reaction in aqueous
      solution, leading to the formation of AuNP-[1]rotaxane hybrids. Corresponding non
      self-included beta-CD derivative functionalized AuNPs were also developed in a
      DMF/H(2)O mixture solution for control experiments. These hybrids were fully
      characterized by UV-vis and circular dichroism spectroscopies, together with
      transmission electron microscopy (TEM). The competitive binding behavior of the
      hybrids with an adamantane dimer was investigated.

PMID- 22949852
TI  - Epigenetic effects of environmental chemicals bisphenol A and phthalates.
AB  - The epigenetic effects on DNA methylation, histone modification, and expression
      of non-coding RNAs (including microRNAs) of environmental chemicals such as
      bisphenol A (BPA) and phthalates have expanded our understanding of the etiology
      of human complex diseases such as cancers and diabetes. Multiple lines of
      evidence from in vitro and in vivo models have established that epigenetic
      modifications caused by in utero exposure to environmental toxicants can induce
      alterations in gene expression that may persist throughout life. Epigenetics is
      an important mechanism in the ability of environmental chemicals to influence
      health and disease, and BPA and phthalates are epigenetically toxic. The
      epigenetic effect of BPA was clearly demonstrated in viable yellow mice by
      decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating
      effect of BPA was prevented by maternal dietary supplementation with a methyl
      donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be
      trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell
      line and mice. BPA exposure of human placental cell lines has been shown to alter
      microRNA expression levels, and specifically, miR-146a was strongly induced by
      BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate
      BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG
      islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant
      DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase
      DNA methylation and expression levels of DNA methyltransferases in mouse testis.
      Further, some epigenetic effects of BPA and phthalates in female rats were found
      to be transgenerational. Finally, the available new technologies for global
      analysis of epigenetic alterations will provide insight into the extent and
      patterns of alterations between human normal and diseased tissues. In vitro
      models such as human embryonic stem cells may be extremely useful in bettering
      the understanding of epigenetic effects on human development, health and disease,
      because the formation of embryoid bodies in vitro is very similar to the early
      stage of embryogenesis.

PMID- 22949853
TI  - The Opuntia streptacantha OpsHSP18 gene confers salt and osmotic stress tolerance
      in Arabidopsis thaliana.
AB  - Abiotic stress limits seed germination, plant growth, flowering and fruit
      quality, causing economic decrease. Small Heat Shock Proteins (sHSPs) are
      chaperons with roles in stress tolerance. Herein, we report the functional
      characterization of a cytosolic class CI sHSP (OpsHSP18) from Opuntia
      streptacantha during seed germination in Arabidopsis thaliana transgenic lines
      subjected to different stress and hormone treatments. The over-expression of the
      OpsHSP18 gene in A. thaliana increased the seed germination rate under salt
      (NaCl) and osmotic (glucose and mannitol) stress, and in ABA treatments, compared
      with WT. On the other hand, the over-expression of the OpsHSP18 gene enhanced
      tolerance to salt (150 mM NaCl) and osmotic (274 mM mannitol) stress in
      Arabidopsis seedlings treated during 14 and 21 days, respectively. These plants
      showed increased survival rates (52.00 and 73.33%, respectively) with respect to
      the WT (18.75 and 53.75%, respectively). Thus, our results show that OpsHSP18
      gene might have an important role in abiotic stress tolerance, in particular in
      seed germination and survival rate of Arabidopsis plants under unfavorable
      conditions.

PMID- 22949854
TI  - Helicobacter pylori disrupts host cell membranes, initiating a repair response
      and cell proliferation.
AB  - Helicobacter pylori (H. pylori), the human stomach pathogen, lives on the inner
      surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric
      cancer. Plasma membrane repair response is a matter of life and death for human
      cells against physical and biological damage. We here test the hypothesis that H.
      pylori also causes plasma membrane disruption injury, and that not only a
      membrane repair response but also a cell proliferation response are thereby
      activated. Vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA)
      have been considered to be major H. pylori virulence factors. Gastric cancer
      cells were infected with H. pylori wild type (vacA+/cagA+), single mutant
      (DeltavacA or DeltacagA) or double mutant (DeltavacA/DeltacagA) strains and
      plasma membrane disruption events and consequent activation of membrane repair
      components monitored. H. pylori disrupts the host cell plasma membrane, allowing
      localized dye and extracellular Ca(2+) influx. Ca(2+)-triggered members of the
      annexin family, A1 and A4, translocate, in response to injury, to the plasma
      membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2,
      increases. Additional forms of plasma membrane disruption, unrelated to H. pylori
      exposure, also promote host cell proliferation. We propose that H. pylori
      activation of a plasma membrane repair is pro-proliferative. This study might
      therefore provide new insight into potential mechanisms of H. pylori-induced
      gastric carcinogenesis.

PMID- 22949855
TI  - Structural and oxidative changes in the kidney of crucian carp induced by silicon
      based quantum dots.
AB  - Silicon-based quantum dots were intraperitoneally injected in Carassius auratus
      gibelio specimens and, over one week, the effects on renal tissue were
      investigated by following their distribution and histological effects, as well as
      antioxidative system modifications. After three and seven days, detached
      epithelial cells from the basal lamina, dilated tubules and debris in the lumen
      of tubules were observed. At day 7, nephrogenesis was noticed. The reduced
      glutathione (GSH) concentration decreased in the first three days and started to
      rise later on. The superoxide dismutase (SOD) activity increased only after one
      week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The
      activities of glutathione reductase (GR) and glutathione peroxidise (GPX)
      decreased dramatically by approximately 50% compared to control, whereas the
      glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH)
      increased significantly after 3 and 7 days of treatment. Oxidative modifications
      of proteins and the time-dependent increase of Hsp70 expression were also
      registered. Our data suggest that silicon-based quantum dots induced oxidative
      stress followed by structural damages. However, renal tissue is capable of
      restoring its integrity by nephron development.

PMID- 22949857
TI  - Bone marrow-derived HipOP cell population is markedly enriched in
      osteoprogenitors.
AB  - We recently succeeded in purifying a novel multipotential progenitor or stem cell
      population from bone marrow stromal cells (BMSCs). This population exhibited a
      very high frequency of colony forming units-osteoblast (CFU-O; 100 times higher
      than in BMSCs) and high expression levels of osteoblast differentiation markers.
      Furthermore, large masses of mineralized tissue were observed in in vivo
      transplants with this new population, designated highly purified osteoprogenitors
      (HipOPs). We now report the detailed presence and localization of HipOPs and
      recipient cells in transplants, and demonstrate that there is a strong
      relationship between the mineralized tissue volume formed and the transplanted
      number of HipOPs.

PMID- 22949856
TI  - Mitochondrial adaptations to oxidative stress confer resistance to apoptosis in
      lymphoma cells.
AB  - Acquired resistance to drugs commonly used for lymphoma treatment poses a
      significant barrier to improving lymphoma patient survival. Previous work with a
      lymphoma tissue culture model indicates that selection for resistance to
      oxidative stress confers resistance to chemotherapy-induced apoptosis. This
      suggests that adaptation to chronic oxidative stress can contribute to
      chemoresistance seen in lymphoma patients. Oxidative stress-resistant WEHI7.2
      cell variants in a lymphoma tissue culture model exhibit a range of apoptosis
      sensitivities. We exploited this phenotype to test for mitochondrial changes
      affecting sensitivity to apoptosis in cells made resistant to oxidative stress.
      We identified impaired release of cytochrome c, and the intermembrane proteins
      adenylate kinase 2 and Smac/DIABLO, indicating inhibition of the pathway leading
      to permeabilization of the outer mitochondrial membrane. Blunting of a
      glucocorticoid-induced signal and intrinsic mitochondrial resistance to
      cytochrome c release contributed to both points of resistance. The level of Bcl-2
      family members or a difference in Bim induction were not contributing factors.
      The extent of cardiolipin oxidation following dexamethasone treatment, however,
      did correlate with apoptosis resistance. The differences found in the variants
      were all proportionate to the degree of resistance to glucocorticoid treatment.
      We conclude that tolerance to oxidative stress leads to mitochondrial changes
      that confer resistance to apoptosis.

PMID- 22949858
TI  - The complete mitochondrial genome of the pink stem borer, Sesamia inferens, in
      comparison with four other Noctuid moths.
AB  - The complete 15,413-bp mitochondrial genome (mitogenome) of Sesamia inferens
      (Walker) (Lepidoptera: Noctuidae) was sequenced and compared with those of four
      other noctuid moths. All of the mitogenomes analyzed displayed similar
      characteristics with respect to gene content, genome organization, nucleotide
      comparison, and codon usages. Twelve-one protein-coding genes (PCGs) utilized the
      standard ATN, but the cox1 gene used CGA as the initiation codon; cox1, cox2, and
      nad4 genes had the truncated termination codon T in the S. inferens mitogenome.
      All of the tRNA genes had typical cloverleaf secondary structures except for
      trnS1(AGN), in which the dihydrouridine (DHU) arm did not form a stable stem-loop
      structure. Both the secondary structures of rrnL and rrnS genes inferred from the
      S. inferens mitogenome closely resembled those of other noctuid moths. In the A+T
      rich region, the conserved motif "ATAGA" followed by a long T-stretch was
      observed in all noctuid moths, but other specific tandem-repeat elements were
      more variable. Additionally, the S. inferens mitogenome contained a potential
      stem-loop structure, a duplicated 17-bp repeat element, a decuplicated segment,
      and a microsatellite "(AT)(7)", without a poly-A element upstream of the trnM in
      the A+T-rich region. Finally, the phylogenetic relationships were reconstructed
      based on amino acid sequences of mitochondrial 13 PCGs, which support the
      traditional morphologically based view of relationships within the Noctuidae.

PMID- 22949859
TI  - Evaluation of antioxidant properties and mineral composition of Purslane
      (Portulaca oleracea L.) at different growth stages.
AB  - The main objective of this research was to appraise the changes in mineral
      content and antioxidant attributes of Portulaca oleracea over different growth
      stages. The antioxidant activity was measured using 1,1-diphenyl-2-picrylhydrazyl
      (DPPH), ferric-reducing antioxidant power (FRAP) assays. The iodine titration
      method was used to determine the ascorbic acid content (AAC). DPPH scavenging
      (IC(50)) capacity ranged from 1.30 +/- 0.04 to 1.71 +/- 0.04 mg/mL, while the
      ascorbic acid equivalent antioxidant activity (AEAC) values were 229.5 +/- 7.9 to
      319.3 +/- 8.7 mg AA/100 g, total phenol content (TPC) varied from 174.5 +/- 8.5
      to 348.5 +/- 7.9 mg GAE/100 g. AAC 60.5 +/- 2.1 to 86.5 +/- 3.9 mg/100 g and FRAP
      1.8 +/- 0.1 to 4.3 +/- 0.1 mg GAE/g. There was good correlation between the
      results of TPC and AEAC, and between IC(50) and FRAP assays (r(2) > 0.9). The
      concentrations of Ca, Mg, K, Fe and Zn increased with plant maturity. Calcium
      (Ca) was negatively correlated with sodium (Na) and chloride (Cl), but positively
      correlated with magnesium (Mg), potassium (K), iron (Fe) and zinc (Zn). Portulaca
      olerecea cultivars could be used as a source of minerals and antioxidants,
      especially for functional food and nutraceutical applications.

PMID- 22949861
TI  - Effects of humidity and surfaces on the melt crystallization of ibuprofen.
AB  - Melt crystallization of ibuprofen was studied to understand the effects of
      humidity and surfaces. The molecular self-assembly during the amorphous-to
      crystal transformation was examined in terms of the nucleation and growth of the
      crystals. The crystallization was on Al, Au, and self-assembled monolayers with 
      CH(3), -OH, and -COOH functional groups. Effects of the humidity were studied at
      room temperature (18-20  degrees C) with relative humidity 33%, 75%, and 100%.
      Effects of the surfaces were observed at -20  degrees C (relative humidity 36%)
      to enable close monitoring with slower crystal growth. The nucleation time of
      ibuprofen was faster at high humidity conditions probably due to the local
      formation of the unfavorable ibuprofen melt/water interface. The crystal
      morphologies of ibuprofen were governed by the nature of the surfaces, and they
      could be associated with the growth kinetics by the Avrami equation. The current
      study demonstrated the effective control of the melt crystallization of ibuprofen
      through the melt/atmosphere and melt/surface interfaces.

PMID- 22949862
TI  - Comparative characterization of total flavonol glycosides and terpene lactones at
      different ages, from different cultivation sources and genders of Ginkgo biloba
      leaves.
AB  - The extract from Ginkgo biloba leaves has become a very popular plant medicine
      and herbal supplement for its potential benefit in alleviating symptoms
      associated with peripheral vascular disease, dementia, asthma and tinnitus. Most
      research on G. biloba leaves focus on the leaves collected in July and August
      from four to seven year-old trees, however a large number of leaves from fruit
      cultivars (trees older than 10 years) are ignored and become obsolete after fruit
      harvest season (November). In this paper, we expand the tree age range (from one
      to 300 years) and first comparatively analyze the total flavonol glycosides and
      terpene lactones at different ages, from different cultivation sources and
      genders of G. biloba leaves collected in November by using the validated HPLC
      ELSD and HPLC-PDA methods. The results show that the contents of total terpene
      lactones and flavonol glycosides in the leaves of young ginkgo trees are higher
      than those in old trees, and they are higher in male trees than in female trees.
      Geographical factors appear to have a significant influence on the contents as
      well. These results will provide a good basis for the comprehensive utilization
      of G. biloba leaves, especially the leaves from fruit cultivars.

PMID- 22949860
TI  - Biogenesis and mechanism of action of small non-coding RNAs: insights from the
      point of view of structural biology.
AB  - Non-coding RNAs are dominant in the genomic output of the higher organisms being
      not simply occasional transcripts with idiosyncratic functions, but constituting
      an extensive regulatory network. Among all the species of non-coding RNAs, small
      non-coding RNAs (miRNAs, siRNAs and piRNAs) have been shown to be in the core of
      the regulatory machinery of all the genomic output in eukaryotic cells. Small non
      coding RNAs are produced by several pathways containing specialized enzymes that
      process RNA transcripts. The mechanism of action of these molecules is also
      ensured by a group of effector proteins that are commonly engaged within high
      molecular weight protein-RNA complexes. In the last decade, the contribution of
      structural biology has been essential to the dissection of the molecular
      mechanisms involved in the biosynthesis and function of small non-coding RNAs.

PMID- 22949863
TI  - Molecular tools for exploring polyploid genomes in plants.
AB  - Polyploidy is a very common phenomenon in the plant kingdom, where even diploid
      species are often described as paleopolyploids. The polyploid condition may bring
      about several advantages compared to the diploid state. Polyploids often show
      phenotypes that are not present in their diploid progenitors or exceed the range
      of the contributing species. Some of these traits may play a role in heterosis or
      could favor adaptation to new ecological niches. Advances in genomics and
      sequencing technology may create unprecedented opportunities for discovering and
      monitoring the molecular effects of polyploidization. Through this review, we
      provide an overview of technologies and strategies that may allow an in-depth
      analysis of polyploid genomes. After introducing some basic aspects on the origin
      and genetics of polyploids, we highlight the main tools available for genome and
      gene expression analysis and summarize major findings. In the last part of this
      review, the implications of next generation sequencing are briefly discussed. The
      accumulation of knowledge on polyploid formation, maintenance, and divergence at
      whole-genome and subgenome levels will not only help plant biologists to
      understand how plants have evolved and diversified, but also assist plant
      breeders in designing new strategies for crop improvement.

PMID- 22949864
TI  - Effects of rice bran oil on the intestinal microbiota and metabolism of
      isoflavones in adult mice.
AB  - This study examined the effects of rice bran oil (RBO) on mouse intestinal
      microbiota and urinary isoflavonoids. Dietary RBO affects intestinal cholesterol
      absorption. Intestinal microbiota seem to play an important role in isoflavone
      metabolism. We hypothesized that dietary RBO changes the metabolism of
      isoflavonoids and intestinal microbiota in mice. Male mice were randomly divided
      into two groups: those fed a 0.05% daidzein with 10% RBO diet (RO group) and
      those fed a 0.05% daidzein with 10% lard control diet (LO group) for 30 days.
      Urinary amounts of daidzein and dihydrodaidzein were significantly lower in the
      RO group than in the LO group. The ratio of equol/daidzein was significantly
      higher in the RO group (p < 0.01) than in the LO group. The amount of fecal bile
      acids was significantly greater in the RO group than in the LO group. The
      composition of cecal microbiota differed between the RO and LO groups. The
      occupation ratios of Lactobacillales were significantly higher in the RO group (p
      < 0.05). Significant positive correlation (r = 0.591) was observed between the
      occupation ratios of Lactobacillales and fecal bile acid content of two dietary
      groups. This study suggests that dietary rice bran oil has the potential to
      affect the metabolism of daidzein by altering the metabolic activity of
      intestinal microbiota.

PMID- 22949865
TI  - An investigation on the thermal effusivity of nanofluids Containing Al(2)O(3) and
      CuO nanoparticles.
AB  - The thermal effusivity of Al(2)O(3) and CuO nanofluids in different base fluids,
      i.e., deionized water, ethylene glycol and olive oil were investigated. The
      nanofluids, nanoparticles dispersed in base fluids; were prepared by mixing
      Al(2)O(3), CuO nanopowder and the base fluids using sonication with high-powered
      pulses to ensure a good uniform dispersion of nanoparticles in the base fluids.
      The morphology of the particles in the base fluids was investigated by
      transmission electron microscopy (TEM). In this study, a phase frequency scan of
      the front pyroelectric configuration technique, with a thermally thick PVDF
      pyroelectric sensor and sample, was used to measure the thermal effusivity of the
      prepared nanofluids. The experimental results of the thermal effusivity of the
      studied solvents (deionized water, ethylene glycol and olive oil) showed good
      agreement with literature values, and were reduced in the presence of
      nanoparticles. The thermal effusivity of the nanofluid was found to be
      particularly sensitive to its base fluid and the type of nanoparticles.

PMID- 22949866
TI  - Melanogenesis inhibition by homoisoflavavone sappanone A from Caesalpinia sappan.
AB  - Homoisoflavanone, sappanone A, was isolated from Caesalpinia sappan and proven to
      dose-dependently inhibit both melanogenesis and cellular tyrosinase activity via
      repressing tyrosinase gene expression in mouse B16 melanoma cells. To our
      knowledge, sappanone A is the first homoisoflavanone to be discovered with
      melanogenesis inhibitory activity. Our results give a new impetus to the future
      search for other homoisoflavanone melanogenesis inhibitors.

PMID- 22949869
TI  - A density functional theory study on the deformation behaviors of Fe-Si-B
      metallic glasses.
AB  - Density functional theory has been employed to investigate the deformation
      behaviors of glassy Fe-Si-B model systems prepared by ab initio molecular
      dynamics. The atomistic deformation defects which are closely related to the
      local dilation volumes or excess volumes and unstable bonding have been
      systematically analyzed. It has been found that the icosahedral structures are
      relatively stable under shear deformation until fracture occurs. Plastic flow is
      indicated by interruption of percolating icosahedral structures, caused by
      unstable Fe-Si bonding of p-s hybridization in nature.

PMID- 22949867
TI  - Macromolecule-assisted de novo protein folding.
AB  - In the processes of protein synthesis and folding, newly synthesized polypeptides
      are tightly connected to the macromolecules, such as ribosomes, lipid bilayers,
      or cotranslationally folded domains in multidomain proteins, representing a
      hallmark of de novo protein folding environments in vivo. Such linkage effects on
      the aggregation of endogenous polypeptides have been largely neglected, although
      all these macromolecules have been known to effectively and robustly solubilize
      their linked heterologous proteins in fusion or display technology. Thus, their
      roles in the aggregation of linked endogenous polypeptides need to be elucidated
      and incorporated into the mechanisms of de novo protein folding in vivo. In the
      classic hydrophobic interaction-based stabilizing mechanism underlying the
      molecular chaperone-assisted protein folding, it has been assumed that the
      macromolecules connected through a simple linkage without hydrophobic
      interactions and conformational changes would make no effect on the aggregation
      of their linked polypeptide chains. However, an increasing line of evidence
      indicates that the intrinsic properties of soluble macromolecules, especially
      their surface charges and excluded volume, could be important and universal
      factors for stabilizing their linked polypeptides against aggregation. Taken
      together, these macromolecules could act as folding helpers by keeping their
      linked nascent chains in a folding-competent state. The folding assistance
      provided by these macromolecules in the linkage context would give new insights
      into de novo protein folding inside the cell.

PMID- 22949868
TI  - MUC16/CA125 in the context of modular proteins with an annotated role in adhesion
      related processes: in silico analysis.
AB  - Mucin 16 (MUC16) is a type I transmembrane protein, the extracellular portion of
      which is shed after proteolytic degradation and is denoted as CA125 antigen, a
      well known tumor marker for ovarian cancer. Regarding its polypeptide and glycan
      structures, as yet there is no detailed insight into their heterogeneity and
      ligand properties, which may greatly influence its function and biomarker
      potential. This study was aimed at obtaining further insight into the biological
      capacity of MUC16/CA125, using in silico analysis of corresponding mucin
      sequences, including similarity searches as well as GO (gene ontology)-based
      function prediction. The results obtained pointed to the similarities within
      extracellular serine/threonine rich regions of MUC16 to sequences of proteins
      expressed in evolutionary distant taxa, all having in common an annotated role in
      adhesion-related processes. Specifically, a homology to conserved domains from
      the family of herpesvirus major outer envelope protein (BLLF1) was found. In
      addition, the possible involvement of MUC16/CA125 in carbohydrate-binding
      interactions or cellular transport of protein/ion was suggested.

PMID- 22949870
TI  - Identification of tillering node proteins differentially accumulated in barley
      recombinant inbred lines with different juvenile growth habits.
AB  - Barley (Hordeum vulgare L.) is an important cereal crop grown for both the feed
      and malting industries. The allelic dwarfing gene sdw1/denso has been used
      throughout the world to develop commercial barley varieties. Proteomic analysis
      offers a new approach to identify a broad spectrum of genes that are expressed in
      the living system. Two-dimensional electrophoresis and mass spectrometry were
      applied to investigate changes in protein abundance associated with different
      juvenile growth habit as effect of the denso locus in barley homozygous lines
      derived from a Maresi * Pomo cross combination. A total of 31 protein spots were
      revealed that demonstrate quantitative differences in protein abundance between
      the analyzed plants with different juvenile growth habit, and these protein spots
      were selected to be identified by mass spectrometry. Identification was
      successful for 27 spots, and functional annotations of proteins revealed that
      most of them are involved in metabolism and disease/defense-related processes.
      Functions of the identified proteins and their probable influence on the growth
      habit in barley are discussed.

PMID- 22949871
TI  - An iRGD based strategy to study electrochemically the species inside a cell.
AB  - This paper reports a method for electrical communication between the inner part
      of cells and an electrode with the help of iRGD peptide. Due to the enhancement
      of the cell penetration caused by iRGD peptide, DNA molecules, previously
      modified on a gold electrode surface, can be easily transfected into the cells.
      At the same time, doxorubicin, an anticancer drug, can also be transfected into
      cells with high penetration. Consequently, doxorubicin binds to DNA chains
      through electrostatic interaction, and the redox reaction is transferred out of
      the cell across the cell membrane. As a result, this work may provide a novel way
      to get information from inside of cells.

PMID- 22949872
TI  - An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin
      F, and its anti-inflammatory activity.
AB  - A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible
      fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by
      comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is
      valuable for further biological studies. The present study is the first total
      synthesis of benzocamphorin F and the developed strategy described is a more
      efficient procedure that allowe the large-scale production of benzocamphorin F
      for further research of the biological activity both in vitro and in vivo.

PMID- 22949873
TI  - Species differentiation of Chinese mollitrichosiphum (Aphididae: greenideinae)
      driven by geographical isolation and host plant acquirement.
AB  - The impact of both the uplift of the Qinghai-Tibetan Plateau (QTP) and the
      separation of the Taiwan and Hainan Islands on the evolution of the fauna and
      flora in adjacent regions has been a topic of considerable interest.
      Mollitrichosiphum is a polyphagous insect group with a wide range of host plants
      (14 families) and distributions restricted to Southeast Asia. Based on the
      mitochondrial Cytochrome C Oxidase Subunit I (COI) and Cytochrome b (Cytb) genes,
      the nuclear elongation factor-1alpha (EF-1alpha) gene, and the detailed
      distribution and host plant data, we investigated the species differentiation
      modes of the Chinese Mollitrichosiphum species. Phylogenetic analyses supported
      the monophyly of Mollitrichosiphum. The divergence time of Mollitrichosiphum
      tenuicorpus (c. 11.0 mya (million years ago)), Mollitrichosiphum nandii and
      Mollitrichosiphum montanum (c. 10.6 mya) was within the time frame of the uplift
      of the QTP. Additionally, basal species mainly fed on Fagaceae, while species
      that fed on multiple plants diverged considerably later. Ancestral state
      reconstruction suggests that Fagaceae may be the first acquired host, and the
      acquisition of new hosts and the expansion of host range may have promoted
      species differentiation within this genus. Overall, it can be concluded that
      geographical isolation and the expansion of the host plant range may be the main
      factors driving species differentiation of Mollitrichosiphum.

PMID- 22949874
TI  - Transforming growth Factor-Beta-Induced Protein (TGFBI)/(betaig-H3): a matrix
      protein with dual functions in ovarian cancer.
AB  - Transforming growth factor-beta-induced protein (TGFBI, also known as betaig-H3
      and keratoepithelin) is an extracellular matrix protein that plays a role in a
      wide range of physiological and pathological conditions including diabetes,
      corneal dystrophy and tumorigenesis. Many reports indicate that betaig-H3
      functions as a tumor suppressor. Loss of betaig-H3 expression has been described
      in several cancers including ovarian cancer and promoter hypermethylation has
      been identified as an important mechanism for the silencing of the TGFBI gene.
      Our recent findings that betaig-H3 is down-regulated in ovarian cancer and that
      high concentrations of betaig-H3 can induce ovarian cancer cell death support a
      tumor suppressor role. However, there is also convincing data in the literature
      reporting a tumor-promoting role for betaig-H3. We have shown betaig-H3 to be
      abundantly expressed by peritoneal cells and increase the metastatic potential of
      ovarian cancer cells by promoting cell motility, invasion, and adhesion to
      peritoneal cells. Our findings suggest that betaig-H3 has dual functions and can
      act both as a tumor suppressor or tumor promoter depending on the tumor
      microenvironment. This article reviews the current understanding of betaig-H3
      function in cancer cells with particular focus on ovarian cancer.

PMID- 22949876
TI  - A novel cyclodextrin glycosyltransferase from Alkaliphilic Amphibacillus sp. NPST
      10: purification and properties.
AB  - Screening for cyclodextrin glycosyltransferase (CGTase)-producing alkaliphilic
      bacteria from samples collected from hyper saline soda lakes (Wadi Natrun Valley,
      Egypt), resulted in isolation of potent CGTase producing alkaliphilic bacterium,
      termed NPST-10. 16S rDNA sequence analysis identified the isolate as
      Amphibacillus sp. CGTase was purified to homogeneity up to 22.1 fold by starch
      adsorption and anion exchange chromatography with a yield of 44.7%. The purified
      enzyme was a monomeric protein with an estimated molecular weight of 92 kDa using
      SDS-PAGE. Catalytic activities of the enzyme were found to be 88.8 U mg(-1)
      protein, 20.0 U mg(-1) protein and 11.0 U mg(-1) protein for cyclization,
      coupling and hydrolytic activities, respectively. The enzyme was stable over a
      wide pH range from pH 5.0 to 11.0, with a maximal activity at pH 8.0. CGTase
      exhibited activity over a wide temperature range from 45  degrees C to 70 
      degrees C, with maximal activity at 50  degrees C and was stable at 30  degrees C
      to 55  degrees C for at least 1 h. Thermal stability of the purified enzyme could
      be significantly improved in the presence of CaCl(2). K(m) and V(max) values were
      estimated using soluble starch as a substrate to be 1.7 +/- 0.15 mg/mL and 100 +/
      2.0 MUmol/min, respectively. CGTase was significantly inhibited in the presence
      of Co(2+), Zn(2+), Cu(2+), Hg(2+), Ba(2+), Cd(2+), and 2-mercaptoethanol. To the
      best of our knowledge, this is the first report of CGTase production by
      Amphibacillus sp. The achieved high conversion of insoluble raw corn starch into
      cyclodextrins (67.2%) with production of mainly beta-CD (86.4%), makes
      Amphibacillus sp. NPST-10 desirable for the cyclodextrin production industry.

PMID- 22949877
TI  - Gender related differences in kidney injury induced by mercury.
AB  - The aim of this study was to determine if there are sex-related differences in
      the acute kidney injury induced by HgCl(2) since female rats express lower levels
      of renal Oat1 and Oat3 (transporters involved in renal uptake of mercury) as
      compared with males. Control males and females and Hg-treated male and female
      Wistar rats were employed. Animals were treated with HgCl(2) (4 mg/kg body weight
      (b.w.), intraperitoneal (i.p.)) 18 h before the experiments. HgCl(2) induced
      renal impairment both in male and female rats. However, female rats showed a
      lower renal impairment than male rats. The observed increase in kidney
      weight/body weight ratio seen in male and female rats following HgCl(2) treatment
      was less in the female rats. Urine volume and creatinine clearance decreased and
      Oat5 urinary excretion increased in both males and females, but to a lesser
      degree in the latter. Urinary alkaline phosphatase (AP) activity and histological
      parameters were modified in male but not in female rats after HgCl(2)
      administration. These results indicate that the lower Oat1 and Oat3 expression in
      the kidney of females restricts Hg uptake into renal cells protecting them from
      this metal toxicity. These gender differences in renal injury induced by mercury
      are striking and also indicate that Oat1 and Oat3 are among the main transporters
      responsible for HgCl(2)-induced renal injury.

PMID- 22949875
TI  - The role of free radicals in the aging brain and Parkinson's Disease: convergence
      and parallelism.
AB  - Free radical production and their targeted action on biomolecules have roles in
      aging and age-related disorders such as Parkinson's disease (PD). There is an age
      associated increase in oxidative damage to the brain, and aging is considered a
      risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade
      with aging; however, the rate and intensity of neuronal loss in patients with PD
      is more marked than that of aging. Here, we enumerate the common link between
      aging and PD at the cellular level with special reference to oxidative damage
      caused by free radicals. Oxidative damage includes mitochondrial dysfunction,
      dopamine auto-oxidation, alpha-synuclein aggregation, glial cell activation,
      alterations in calcium signaling, and excess free iron. Moreover, neurons
      encounter more oxidative stress as a counteracting mechanism with advancing age
      does not function properly. Alterations in transcriptional activity of various
      pathways, including nuclear factor erythroid 2-related factor 2, glycogen
      synthase kinase 3beta, mitogen activated protein kinase, nuclear factor kappa B,
      and reduced activity of superoxide dismutase, catalase and glutathione with aging
      might be correlated with the increased incidence of PD.

PMID- 22949878
TI  - Characterization of aptamer-protein complexes by X-ray crystallography and
      alternative approaches.
AB  - Aptamers are oligonucleotide ligands, either RNA or ssDNA, selected for high
      affinity binding to molecular targets, such as small organic molecules, proteins
      or whole microorganisms. While reports of new aptamers are numerous,
      characterization of their specific interaction is often restricted to the
      affinity of binding (K(D)). Over the years, crystal structures of aptamer-protein
      complexes have only scarcely become available. Here we describe some relevant
      technical issues about the process of crystallizing aptamer-protein complexes and
      highlight some biochemical details on the molecular basis of selected aptamer
      protein interactions. In addition, alternative experimental and computational
      approaches are discussed to study aptamer-protein interactions.

PMID- 22949879
TI  - Direct observation of protein microcrystals in crystallization buffer by
      atmospheric scanning electron microscopy.
AB  - X-ray crystallography requires high quality crystals above a given size. This
      requirement not only limits the proteins to be analyzed, but also reduces the
      speed of the structure determination. Indeed, the tertiary structures of many
      physiologically important proteins remain elusive because of the so-called
      "crystallization bottleneck". Once microcrystals have been obtained,
      crystallization conditions can be optimized to produce bigger and better
      crystals. However, the identification of microcrystals can be difficult due to
      the resolution limit of optical microscopy. Electron microscopy has sometimes
      been utilized instead, with the disadvantage that the microcrystals usually must
      be observed in vacuum, which precludes the usage for crystal screening. The
      atmospheric scanning electron microscope (ASEM) allows samples to be observed in
      solution. Here, we report the use of this instrument in combination with a
      special thin-membrane dish with a crystallization well. It was possible to
      observe protein crystals of lysozyme, lipase B and a histone chaperone TAF-Ibeta
      in crystallization buffers, without the use of staining procedures. The smallest
      crystals observed with ASEM were a few MUm in width, and ASEM can be used with
      non-transparent solutions. Furthermore, the growth of salt crystals could be
      monitored in the ASEM, and the difference in contrast between salt and protein
      crystals made it easy to distinguish between these two types of microcrystals.
      These results indicate that the ASEM could be an important new tool for the
      screening of protein microcrystals.

PMID- 22949880
TI  - Deciphering the molecular nature of ovarian cancer biomarker CA125.
AB  - The ovarian cancer biomarker CA125 has been extensively investigated over the
      last 30 years. The knowledge about the exact molecular nature of this protein,
      however, remains fragmented. This review provides an overview of the structural
      research regarding CA125, and presents an orthogonal verification method to
      confirm the identity of this molecule. The need for independent identification of
      CA125 is exemplified by several reports where mutually exclusive data concerning
      the existence of isoforms and the glycan moieties is presented. Mass spectrometry
      can overcome the pitfalls of a single detection/identification method such as
      antibody probing. Independent verification of CA125 identity in characterization
      studies will help establish a refined model of its molecular structure that will
      promote the development of new approaches for diagnosis, prognosis and therapy of
      ovarian cancer.

PMID- 22949881
TI  - Development of microsatellite markers for the Korean Mussel, Mytilus coruscus
      (Mytilidae) using next-generation sequencing.
AB  - Mytilus coruscus (family Mytilidae) is one of the most important marine shellfish
      species in Korea. During the past few decades, this species has become endangered
      due to the loss of habitats and overfishing. Despite this species' importance,
      information on its genetic background is scarce. In this study, we developed
      microsatellite markers for M. coruscus using next-generation sequencing. A total
      of 263,900 raw reads were obtained from a quarter-plate run on the 454 GS-FLX
      titanium platform, and 176,327 unique sequences were generated with an average
      length of 381 bp; 2569 (1.45%) sequences contained a minimum of five di- to tetra
      nucleotide repeat motifs. Of the 51 loci screened, 46 were amplified
      successfully, and 22 were polymorphic among 30 individuals, with seven of
      trinucleotide repeats and three of tetranucleotide repeats. All loci exhibited
      high genetic variability, with an average of 17.32 alleles per locus, and the
      mean observed and expected heterozygosities were 0.67 and 0.90, respectively. In
      addition, cross-amplification was tested for all 22 loci in another congener
      species, M. galloprovincialis. None of the primer pairs resulted in effective
      amplification, which might be due to their high mutation rates. Our work
      demonstrated the utility of next-generation 454 sequencing as a method for the
      rapid and cost-effective identification of microsatellites. The high degree of
      polymorphism exhibited by the 22 newly developed microsatellites will be useful
      in future conservation genetic studies of this species.

PMID- 22949882
TI  - Antisense oligonucleotide against clusterin regulates human hepatocellular
      carcinoma invasion through transcriptional regulation of matrix metalloproteinase
      2 and E-cadherin.
AB  - Secreted clusterin (sCLU) has been shown to be overexpressed in metastatic
      hepatocellular carcinoma (HCC) tissue, and its overexpression in HCC cells
      increases cell migration and the formation of liver metastatic tumor nodules in
      vivo. In this study, we tested the hypothesis that sCLU plays a role in the
      invasiveness of human HCC and may be associated with its metastatic spread.
      HCCLM3, a human hepatocellular carcinoma cell line, was transiently transfected
      with an antisense oligonucleotide (ASO) against sCLU (OGX-011). HepG2 liver
      hepatocellular cells were transiently transfected with the pc.DNA3.1-sCLU plasmid
      to overexpress sCLU, and subsequently evaluated for effects on invasion and the
      expression of molecules involved in invasion. We observed that suppression of the
      sCLU gene significantly reduced the invasive capability of the highly invasive
      HCCLM3 cells, and vice versa in the low invasive HepG2 cell line. The results
      revealed that knockdown of sCLU by OGX-011 resulted in a significant increase in
      the expression of E-cadherin and a decrease in matrix metalloproteinase-2 (MMP-2)
      gene transcription. Overexpression of sCLU by transfection with pc.DNA3.1-sCLU
      significantly decreased the expression of E-cadherin and increased MMP-2 gene
      transcription. These data were further verified by reverse transcription-PCR and
      Western blot analysis. A significant reduction in MMP-2 expression and an
      increase in E-cadherin expression in sCLU-knockdown HCCLM3 cells were observed,
      as well as a significant increase in MMP-2 expression and a decrease in E
      cadherin expression in HepG2 cells overexpressing sCLU. These data indicate a
      role for sCLU in augmenting MMP-2 transcription and decreasing E-cadherin
      expression. Our data show the involvement of sCLU in human HCC invasion, and
      demonstrate that silencing sCLU gene expression inhibits the invasion of human
      HCC cells by inhibiting MMP-2 expression and promoting E-cadherin expression.
      Thus, OGX-011 could be an effective therapeutic agent for HCC.

PMID- 22949884
TI  - Optimization of Xylanase production from Penicillium sp.WX-Z1 by a two-step
      statistical strategy: Plackett-Burman and Box-Behnken experimental design.
AB  - The objective of the study was to optimize the nutrition sources in a culture
      medium for the production of xylanase from Penicillium sp.WX-Z1 using Plackett
      Burman design and Box-Behnken design. The Plackett-Burman multifactorial design
      was first employed to screen the important nutrient sources in the medium for
      xylanase production by Penicillium sp.WX-Z1 and subsequent use of the response
      surface methodology (RSM) was further optimized for xylanase production by Box
      Behnken design. The important nutrient sources in the culture medium, identified
      by the initial screening method of Placket-Burman, were wheat bran, yeast
      extract, NaNO(3), MgSO(4), and CaCl(2). The optimal amounts (in g/L) for maximum
      production of xylanase were: wheat bran, 32.8; yeast extract, 1.02; NaNO(3),
      12.71; MgSO(4), 0.96; and CaCl(2), 1.04. Using this statistical experimental
      design, the xylanase production under optimal condition reached 46.50 U/mL and an
      increase in xylanase activity of 1.34-fold was obtained compared with the
      original medium for fermentation carried out in a 30-L bioreactor.

PMID- 22949883
TI  - Recent advances on the neuroprotective potential of antioxidants in experimental
      models of Parkinson's disease.
AB  - Parkinson's disease (PD), a neurodegenerative movement disorder of the central
      nervous system (CNS) is characterized by a progressive loss of dopaminergic
      neurons in the substantia nigra pars compacta region of the midbrain. Although
      the etiology of PD is not completely understood and is believed to be
      multifactorial, oxidative stress and mitochondrial dysfunction are widely
      considered major consequences, which provide important clues to the disease
      mechanisms. Studies have explored the role of free radicals and oxidative stress
      that contributes to the cascade of events leading to dopamine cell degeneration
      in PD. In general, in-built protective mechanisms consisting of enzymatic and non
      enzymatic antioxidants in the CNS play decisive roles in preventing neuronal cell
      loss due to free radicals. But the ability to produce these antioxidants
      decreases with aging. Therefore, antioxidant therapy alone or in combination with
      current treatment methods may represent an attractive strategy for treating or
      preventing the neurodegeneration seen in PD. Here we summarize the recent
      discoveries of potential antioxidant compounds for modulating free radical
      mediated oxidative stress leading to neurotoxicity in PD.

PMID- 22949886
TI  - Spontaneous transformation of stem cells in vitro and the issue of cross
      contamination.

PMID- 22949885
TI  - Molecular mechanisms of oligodendrocyte injury in multiple sclerosis and
      experimental autoimmune encephalomyelitis.
AB  - New evidence has emerged over the last decade indicating that oligodendrocyte
      injury in multiple sclerosis (MS) is not a single unified phenomenon but rather a
      spectrum of processes ranging from massive immune destruction to a subtle cell
      death in the absence of significant inflammation. Experimentally, protection of
      oligodendrocytes against inflammatory injury results in protection against
      experimental autoimmune encephalitis, the animal model of multiple sclerosis. In
      this review, we will discuss the molecular mechanisms regulating oligodendrocyte
      injury and inflammatory demyelination. We draw attention to the injurious role of
      IFN-gamma signaling in oligodendrocytes and the pro-inflammatory effect of their
      death. In conclusion, studying the molecular mechanisms of oligodendrocyte injury
      is likely to provide new perspective on the pathogenesis of MS and a rationale
      for cell protective therapies.

PMID- 22949888
TI  - Protein interactions on telomeric retrotransposons in Drosophila.
AB  - Telomere length in Drosophila is maintained by targeted transposition of three
      non-LTR retrotransposons: HeT-A, TART and TAHRE (HTT), but understanding the
      regulation of this process is hindered by our poor knowledge of HTT associated
      proteins. We have identified new protein components of the HTT array: Chromator
      (Chro), the TRF2/DREF complex and the sumoylation machinery. Chro was localized
      on telomeric HTT arrays by immunostaining, where it may interact with Prod
      directly, as indicated by yeast two-hybrid interaction, co-IP, and colocalization
      on polytene chromosomes. The TRF2/DREF complex may promote the open structure of
      HTT chromatin. The protein interactions controlling HTT chromatin structure and
      telomere length may be modulated by sumoylation.

PMID- 22949889
TI  - TGF-beta-operated growth inhibition and translineage commitment into smooth
      muscle cells of periodontal ligament-derived endothelial progenitor cells through
      Smad- and p38 MAPK-dependent signals.
AB  - The periodontal ligament (PDL) is a fibrous connective tissue that attaches the
      tooth to the alveolar bone. We previously demonstrated the ability of PDL
      fibroblast-like cells to construct an endothelial cell (EC) marker-positive blood
      vessel-like structure, indicating the potential of fibroblastic lineage cells in
      PDL tissue as precursors of endothelial progenitor cells (EPCs) to facilitate the
      construction of a vascular system around damaged PDL tissue. A vascular
      regeneration around PDL tissue needs proliferation of vascular progenitor cells
      and the subsequent differentiation of the cells. Transforming growth factor-beta
      (TGF-beta) is known as an inducer of endothelial-mesenchymal transition (EndMT),
      however, it remains to be clarified what kinds of TGF-beta signals affect growth
      and mesenchymal differentiation of PDL-derived EPC-like fibroblastic cells. Here,
      we demonstrated that TGF-beta1 not only suppressed the proliferation of the PDL
      derived EPC-like fibroblastic cells, but also induced smooth muscle cell (SMC)
      markers expression in the cells. On the other hand, TGF-beta1 stimulation
      suppressed EC marker expression. Intriguingly, overexpression of Smad7, an
      inhibitor for TGF-beta-induced Smad-dependent signaling, suppressed the TGF-beta1
      induced growth inhibition and SMC markers expression, but did not the TGF-beta1
      induced downregulation of EC marker expression. In contrast, p38 mitogen
      activated protein kinase (MAPK) inhibitor SB 203580 suppressed the TGF-beta1
      induced downregulation of EC marker expression. In addition, the TGF-beta1
      induced SMC markers expression of the PDL-derived cells was reversed upon
      stimulation with fibroblast growth factor (FGF), suggesting that the TGF-beta1
      might not induce terminal SMC differentiation of the EPC-like fibroblastic cells.
      Thus, TGF-beta1 not only negatively controls the growth of PDL-derived EPC-like
      fibroblastic cells via a Smad-dependent manner but also positively controls the
      SMC-differentiation of the cells possibly at the early stage of the translineage
      commitment via Smad- and p38 MAPK-dependent manners.

PMID- 22949891
TI  - Multimodal treatment of hepatic metastasis in the form of a bile duct tumor
      thrombus from pancreatic acinar cell carcinoma: case report of successful
      resection after chemoradiation therapy.
AB  - Pancreatic acinar cell carcinoma (ACC) is a rare tumor, and its pathophysiology
      has not been well understood. Treatment strategies for hepatic metastasis
      originating from ACC remain controversial. We report the case of a 66-year-old
      woman who had undergone total pancreatectomy from ACC 7 years prior to clinical
      presentation. Contrast-enhanced computed tomography imaging revealed a tumorous
      lesion measuring 7 cm in length and 1 cm in diameter and extending along the
      intrahepatic bile duct (B6), which showed mild enhancement in the early phase and
      modest washout in the late phase. This lesion was diagnosed as hepatic metastasis
      primarily in the form of a bile duct tumor thrombus originating from the prior
      ACC by the pathological evaluation of the fine needle biopsy specimen. The
      patient underwent preoperative gemcitabine-based chemoradiation therapy followed
      by subsequent surgical resection, which included subsegmentectomy (S6) of the
      liver and complete removal of the bile duct tumor thrombus. The patient has had
      no recurrence during the past 8 months since her last surgery. Multimodal
      treatment including preoperative chemoradiation therapy might be beneficial
      especially for marginally resectable cases of ACC.

PMID- 22949890
TI  - Reduced activity of protein kinase C in the frontal cortex of subjects with
      regressive autism: relationship with developmental abnormalities.
AB  - Autism is a neurodevelopmental disorder with unknown etiology. In some cases,
      typically developing children regress into clinical symptoms of autism, a
      condition known as regressive autism. Protein kinases are essential for G-protein
      coupled receptor-mediated signal transduction, and are involved in neuronal
      functions, gene expression, memory, and cell differentiation. Recently, we
      reported decreased activity of protein kinase A (PKA) in the frontal cortex of
      subjects with regressive autism. In the present study, we analyzed the activity
      of protein kinase C (PKC) in the cerebellum and different regions of cerebral
      cortex from subjects with regressive autism, autistic subjects without clinical
      history of regression, and age-matched control subjects. In the frontal cortex of
      subjects with regressive autism, PKC activity was significantly decreased by
      57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as
      compared to non-regressed autistic subjects (p = 0.0048). PKC activity was
      unaffected in the temporal, parietal and occipital cortices, and in the
      cerebellum in both autism groups, i.e., regressive and non-regressed autism as
      compared to control subjects. These results suggest brain region-specific
      alteration of PKC activity in the frontal cortex of subjects with regressive
      autism. Further studies showed a negative correlation between PKC activity and
      restrictive, repetitive and stereotyped pattern of behavior (r = -0.084, p =
      0.0363) in autistic individuals, suggesting involvement of PKC in behavioral
      abnormalities in autism. These findings suggest that regression in autism may be
      attributed, in part, to alterations in G-protein-coupled receptor-mediated signal
      transduction involving PKA and PKC in the frontal cortex.

PMID- 22949892
TI  - Common bile duct obstruction secondary to a periampullary diverticulum.
AB  - Periampullary duodenal diverticula are not uncommon and are usually asymptomatic
      although complications may occasionally occur. Here, we report the case of a 72
      year-old woman who presented with painless obstructive jaundice. Laboratory tests
      showed abnormally elevated serum concentrations of total and direct bilirubin, of
      alkaline phosphatase, of gamma-glutamyl transpeptidase, and of aspartate and
      alanine aminotransferases. Serum concentrations of the tumor markers carbohydrate
      antigen 19-9 and carcinoembryonic antigen were normal. Abdominal ultrasonography
      showed dilatation of the common bile duct (CBD), but no gallstones were found
      either in the gallbladder or in the CBD. The gallbladder wall was normal.
      Computed tomography failed to detect the cause of CBD obstruction. Magnetic
      resonance imaging and magnetic resonance cholangiopancreatography revealed a
      periampullary diverticulum measuring 2 cm in diameter and compressing the CBD.
      The pancreatic duct was normal. Hypotonic duodenography demonstrated a
      periampullary diverticulum with a filling defect corresponding to the papilla.
      CBD compression by the diverticulum was considered as the cause of jaundice. The
      patient was successfully treated by surgical excision of the diverticulum. In
      conclusion, the presence of a periampullary diverticulum should be considered in
      elderly patients presenting with obstructive jaundice in the absence of CBD
      gallstones or of a tumor mass. Non-interventional imaging studies should be
      preferred for diagnosis of this condition, and surgical or endoscopic
      interventions should be used judiciously for the effective and safe treatment of
      these patients.

PMID- 22949893
TI  - Preoperative gemcitabine and oxaliplatin in a patient with ovarian metastasis
      from pancreatic cystadenocarcinoma.
AB  - We describe a case of clinical benefit and partial response with gemcitabine and
      oxaliplatin (GEMOX) in a young patient with ovarian metastasis from
      cystadenocarcinoma of the pancreas. A young woman complained of abdominal pain
      and constipation. Computed tomography (CT) and magnetic resonance imaging scans
      disclosed two bilateral ovarian masses with pancreatic extension. She underwent
      bilateral ovarian and womb resection. During surgery peritoneal carcinosis, a
      pancreatic mass and multiple abdominal lesions were found. The final diagnosis
      was mucinous pancreatic cystadenocarcinoma with ovarian and peritoneal
      metastases. She started chemotherapy with GEMOX (gemcitabine 1,000 mg/m(2)/d1 and
      oxaliplatin 100 mg/m(2)/d2 every 2 weeks). After 12 cycles of chemotherapy a CT
      scan showed reduction of the pancreatic mass. She underwent distal pancreatic
      resection, regional lymphadenectomy and splenectomy. Pathologic examination
      documented prominent fibrous tissue and few neoplastic cells with mucin-filled
      cytoplasm. Chemotherapy was continued with gemcitabine as adjuvant treatment for
      another 3 cycles. There is currently no evidence of disease. As reported in the
      literature, GEMOX is associated with an improvement in progression-free survival
      and clinical benefit in patients with advanced pancreatic cancer. This is an
      interesting case in whom GEMOX transformed inoperable pancreatic cancer into a
      resectable tumor.

PMID- 22949894
TI  - Dipeptidyl Peptidase IV Inhibitor Improves Insulin Resistance and Steatosis in a
      Refractory Nonalcoholic Fatty Liver Disease Patient: A Case Report.
AB  - A 67-year-old Asian woman was referred to Kurume University Hospital due to
      abnormal liver function tests. She was diagnosed with nonalcoholic fatty liver
      disease (NAFLD). NAFLD was treated by diet therapy with medication of metformin
      and pioglitazone; however, NAFLD did not improve. Subsequently, the patient was
      administered sitagliptin. Although her energy intake and physical activity did
      not change, her hemoglobin A1c level was decreased from 7.8 to 6.4% 3 months
      after treatment. Moreover, her serum insulin level and homeostasis model
      assessment-insulin resistance value were also improved, as was the severity of
      hepatic steatosis. These findings indicate that sitagliptin may improve insulin
      resistance and steatosis in patients with refractory NAFLD.

PMID- 22949895
TI  - Acute inflammatory bowel disease complicating chronic alcoholism and mimicking
      carcinoid syndrome.
AB  - We report the case of a woman with a history of chronic alcohol abuse who was
      hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion,
      nausea, vomiting, abdominal pain, alternations of high blood pressure with phases
      of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and
      cortisol. Although carcinoid syndrome was hypothesized, abdominal computed
      tomography and colonoscopy showed non-specific inflammatory bowel disease with
      severe colic wall thickening, and multiple colic biopsies confirmed non-specific
      inflammation with no evidence of carcinoid cells. During the following days
      diarrhea slowly decreased and the patient's condition progressively improved. One
      year after stopping alcohol consumption, the patient was asymptomatic and serum
      potassium was normal. Chronic alcohol exposure is known to have several
      deleterious effects on the intestinal mucosa and can favor and sustain local
      inflammation. Chronic alcohol intake may also be associated with high blood
      pressure, behavior disorders, abnormalities in blood pressure regulation with
      episodes of hypotension during hospitalization due to impaired baroreflex
      sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5
      hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased
      urinary cortisol as a result of hypothalamic-pituitary-adrenal axis
      dysregulation. These considerations, together with the regression of symptoms and
      normalization of potassium levels after stopping alcohol consumption, suggest the
      intriguing possibility of a alcohol-related acute inflammatory bowel disease
      mimicking carcinoid syndrome.

PMID- 22949896
TI  - Long-term therapy of a patient with summerskill-walshe-tygstrup syndrome by
      applying prometheus(r) liver dialysis: a case report.
AB  - Summerskill-Walshe-Tygstrup syndrome is a rare benign chronic liver disease
      characterized by recurring cholestasis with jaundice and severe pruritus. Due to
      insufficient conservative treatment, liver dialysis by Prometheus((r)) was
      applied to a 45-year-old female patient with resistant pruritus. Initially, other
      possible liver diseases were excluded and the patient was treated symptomatically
      since the diagnosis of Summerskill-Walshe-Tygstrup was stated in 1998. As
      conservative and endoscopic methods progressively failed to relieve the patient's
      suffering, Prometheus((r)) liver dialysis was performed regularly since 2006 at 3
      month intervals and successfully led to a decrease in the patient's symptoms.
      Cholestatic liver enzymes and also serum bile acids could be lowered
      significantly from an average of 22.5 +/- 2.7 to 7.3 +/- 1.7 umol/l.
      Consequently, Prometheus((r)) liver dialysis may be a beneficial option for
      patients with benign recurrent intrahepatic cholestasis suffering from therapy
      resistant symptoms and may be used as well as other extracorporeal liver support
      devices which have already been reported to improve cholestatic pruritus.

PMID- 22949897
TI  - Unroofing technique for endoscopic resection of a large colonic lipoma.
AB  - A 77-year-old man presented with repeated episodes of melena. He had a medical
      history of hypertension, atrial fibrillation and cardiogenic brain infarction and
      took medications, i.e. an antiplatelet agent. Laboratory data revealed iron
      deficiency anemia. Colonoscopy revealed a yellowish smooth submucosal tumor, 50
      mm in diameter, on the Bauhin valve. The lesion was soft and compressible. The
      overlying mucosa was erosive. CT scan showed a uniform mass with very low density
      in the ascending colon, corresponding to the above-detected lesion. The clinical
      diagnosis of colonic lipoma was established. Using a 25 mm electrocautery snare
      (Olympus, Tokyo, Japan), we transected the upper portion of the mass to unroof
      the lesion. The mucosa layer was thick and hard. Fat tissue was observed
      extruding from the cut surface, consistent with the diagnostic hypothesis. After
      dissecting the overlying mucosa on the anal side by means of an IT knife
      (Olympus) in order to completely extrude the mass, the fat tissue was further
      exposed. It took about 26 min to perform the whole procedure. There were no
      procedure-related complications. Macroscopically, the resected lesion was a
      yellow solid tumor, 1.6 * 1.5 * 0.7 cm in diameter. Histopathologic examination
      of the excised specimen confirmed the diagnosis of a lipoma. The clinical course
      was uneventful. A follow-up endoscopy 1 month later showed a scarred mucosa at
      the resection site. Similarly, a follow-up CT scan 2 months later revealed no
      evidence of residual lipoma. The unroofing technique is safe, easy and suitable
      for the treatment of large lipomas.

PMID- 22949898
TI  - Multicentric reticulohistiocytosis associated with liver carcinoma: report of a
      case.
AB  - We report a unique case of multicentric reticulohistiocytosis (MRH) associated
      with liver carcinoma. A 61-year-old man presented with a 4-month history of
      nonpruritic, generalized, ruby-red papules and nodules, accompanied by fever,
      joint swelling and difficulty in swallowing. Skin histology showed polymorphic
      histiocyte infiltration with typical 'ground glass' cytoplasm. Further
      immunohistochemical studies characterized the lesions as positive for leukocyte
      common antigen, HLA-DR and CD68. The patient had a history of hepatitis B, and
      systemic examination, including carcinoma index and type-B ultrasonic
      examination, revealed high levels of AFP and a solid tumor, which was considered
      malignant, localized on the right lobe of the liver. Treatment of the liver
      carcinoma resulted in a significant improvement of the skin symptoms. This is the
      first case study to report an association between MRH and liver carcinoma. A
      review of the English-language literature reveals the close linkage between MRH
      and malignancy. All patients with MRH should be evaluated and monitored carefully
      to determine the underlying neoplasm.

PMID- 22949899
TI  - A pediatric case of pityriasis rubra pilaris successfully treated with low-dose
      vitamin a.
AB  - Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory keratosis that is
      clinically characterized by gradually developing reddish or orange extending
      plaques and keratotic follicular papules. In pediatric patients, we frequently
      hesitate to administer certain medications for treatment of PRP, specifically
      etretinate, systemic corticosteroids, and biologics recommended by previous
      studies. Although administration of high-dose vitamin A was described in a
      previous textbook of dermatology, details about the lower limits and treatment
      periods were not provided. We presented a pediatric case of PRP that was
      successfully controlled with minimum dosage of systemic vitamin A in the
      literature. Before and 14 days after beginning the therapy, both vitamin A levels
      of peripheral blood were within the normal range. We considered that the clinical
      efficacy may not be due to a supplementary effect of vitamin A, but to a
      pharmacological action because serum vitamin A was within the normal limits
      during the therapy.

PMID- 22949900
TI  - Laugier-hunziker syndrome in a patient with pancreatic cancer.
AB  - Laugier-Hunziker syndrome is a rare acquired disorder characterized by macular
      hyperpigmentation of the oral and occasionally genital mucosa as well as
      longitudinal melanonychia. It is considered a benign condition without systemic
      manifestation or malignant potential. We report on a woman who concomitantly
      developed Laugier-Hunziker syndrome and a carcinoma of the pancreas.

PMID- 22949901
TI  - Clostridium difficile Colitis and Neutropenic Fever Associated with Docetaxel
      Chemotherapy in a Patient with Advanced Extramammary Paget's Disease.
AB  - Extramammary Paget's disease is a rare cutaneous malignant neoplasm. Previous
      studies indicated the efficacy of docetaxel in advanced cases. The common side
      effects of docetaxel are usually tolerable and seldom life-threatening. We
      experienced a case of severe pseudomembranous colitis and neutropenic fever that
      developed just after the first cycle of docetaxel chemotherapy. To the best of
      our knowledge, there are few reports of pseudomembranous colitis associated with
      docetaxel administration for skin cancers. The patient showed complete resolution
      of her symptoms within 2 weeks with an oral metronidazole therapy. During the
      second and third cycles, the patient received docetaxel safely with lower doses.
      The present case indicated that pseudomembranous colitis should be included in
      the differential diagnosis when assessing patients who develop severe diarrhea
      during systemic chemotherapy with docetaxel.

PMID- 22949902
TI  - Comparison and analysis of delirium induced by histamine h(2) receptor
      antagonists and proton pump inhibitors in cancer patients.
AB  - OBJECTIVE: H(2) blockers have been reported to be responsible for drug-induced
      delirium. We compared the incidence of delirium between two groups of patients
      who were treated with H(2) blockers (H(2) group) or proton pump inhibitors (PPI
      group) for anastomotic ulcer prevention following surgical treatment of
      esophageal cancer. METHOD: The incidence and severity of delirium were
      retrospectively compared in patients of the H(2) group (30 cases; age, 65.2 +/-
      8.1 years) and the PPI group (30 cases; 65.2 +/- 6.5 years). The diagnosis of
      delirium was based on the Diagnostic and Statistical Manual of Mental Disorders
      IV-Text Revision. Delirium severity was rated on the Delirium Rating Scale (DRS).
      RESULTS: The incidence of delirium was significantly lower in the PPI group than
      in the H(2) group (p = 0.047). In the 11 patients from the H(2) group who
      developed delirium, discontinuation of H(2) blockers resulted in a significant
      reduction in the DRS score (p = 0.009). In three patients for whom H(2) blockers
      were discontinued, DRS scores decreased by 50% or more three days after
      discontinuation compared to the prediscontinuation score. CONCLUSIONS: These
      results suggested that switching antiulcer drugs from H(2) blockers to PPIs
      reduced delirium and thus provided an appropriate coping method for drug-induced
      delirium from antiulcer drugs.

PMID- 22949903
TI  - Rituximab plus Ifosfamide, Carboplatin and Etoposide for T-Cell/Histiocyte-Rich B
      Cell Lymphoma Arising in Nodular Lymphocyte-Predominant Hodgkin's Lymphoma.
AB  - A small subset of patients with nodular lymphocyte-predominant Hodgkin's lymphoma
      (NLPHLs) develop a non-Hodgkin lymphoma either concurrently or subsequently,
      usually T-cell/histiocyte-rich B-cell lymphomas (T/HRBCL), which are subtypes of
      diffuse large B-cell lymphomas (DLBCL). The standard treatment of DLBCL patients
      is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine
      and prednisolone. However, the administration of this chemotherapy regimen to
      patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of
      anthracycline because the majority of these patients had already received
      anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and
      dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential
      transformation of NLPHL to T/HRBCL. They initially presented with limited-stage
      NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At
      the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin
      and etoposide, and complete responses were obtained.

PMID- 22949904
TI  - Non-islet cell tumor hypoglycemia at the second recurrence of malignant solitary
      fibrous tumor in the retroperitoneum and pelvis: a case report.
AB  - An 83-year-old man underwent complete resection of a large malignant solitary
      fibrous tumor in the retroperitoneum in 2006 and of a local recurrent tumor in
      2010. In 2011, he was admitted to our hospital because of hypoglycemia. His serum
      glucose level was very low, and his levels of insulin and C-peptide were low.
      Furthermore, he had a recurrent tumor in the retroperitoneum and pelvis.
      Immediately after the third surgery for complete resection, he had no
      hypoglycemic episodes and his serum glucose level was within the normal range.
      Immunoblotting analysis revealed a high-molecular-weight form of insulin-like
      growth factor II in the patient's serum and in the protein extract obtained from
      the resected specimen in 2011. To our knowledge, this is the first report of non
      islet cell tumor hypoglycemia caused by a malignant solitary fibrous tumor
      secreting a high-molecular-weight form of insulin-like growth factor II at the
      second recurrence.

PMID- 22949905
TI  - Efficacy of Cetuximab in Combination with FOLFIRI in a Patient with KRAS Wild
      Type Metastatic Anal Cancer.
AB  - Anal canal cancer is a rare tumor without clear treatment evidence in the
      metastatic setting. In terms of the bad prognosis of patients with metastatic
      anal cancer, further therapeutic options are urgently needed. In this paper we
      present the case of a 64-year-old man suffering from undifferentiated squamous
      cell carcinoma with liver metastases. After progression on cisplatin and
      fluorouracil, tumor tissue was analyzed with respect to anti-EGFR therapy with
      cetuximab. There was no KRAS mutation and the EGFR expression level in the tumor
      tissue was 2+; ideal conditions for the immunotherapy. Encouraged by these
      results we started a therapy using FOLFIRI in combination with cetuximab.
      Fortunately the patient showed a partial response after 6 cycles. On patient's
      preference we did a therapy break of 6 weeks. Within this time period the disease
      was progressive indicating its aggressiveness. However, the same immunotherapy
      was able to stabilize the disease for a further 3 months. The patient died 21
      months after diagnosis because of liver failure. Nevertheless, from our
      perspective the combination of FOLFIRI and cetuximab is quite a promising
      therapeutic option for patients with metastatic anal cancer. Potential predictive
      factors of the immunochemotherapy are discussed in this paper.

PMID- 22949906
TI  - A case report of scrotal carcinoma and review of the literature.
AB  - Scrotal carcinoma is a rare tumor. We report one case of such disease in a 60
      year-old man presenting with an ulcerated-bleeding lesion on the left side of the
      scrotum and an enlarged lymph node in the left inguinal region. Biopsy of the
      ulcerated lesion found squamous cell carcinoma of the scrotum. He underwent
      initial tumor resection and left inguinal lymph node biopsy followed by
      postoperative concurrent chemoradiotherapy. Postoperative pathological
      examination confirmed well-differentiated squamous cell carcinoma of the scrotum
      and lymph node metastasis. Five months after the treatment, the size of the lymph
      node was dramatically decreased, with no signs of tumor progression. Surgical
      treatment combined with concurrent chemoradiotherapy may be an appropriate
      management approach to achieve palliative symptom relief for this disease.

PMID- 22949907
TI  - Primary small cell neuroendocrine carcinoma of the endometrium.
AB  - BACKGROUND: Small cell neuroendocrine carcinoma is very rarely encountered within
      the endometrium. CASE STUDY: A patient underwent a hysterectomy and salpingo
      oophorectomy for a suspicious gynecologic condition. Pathology revealed invasive
      small cell neuroendocrine carcinoma of the endometrium; the neoplasm exhibited
      positive immunoreactivity for synaptophysin, pancytokeratin and CD56 but was
      negative for CD3 and CD20. Prior to chemotherapy, a completion lymphadenectomy
      was indicated to determine the presence of nodal metastases. CONCLUSION: The
      prognosis of small cell neuroendocrine carcinoma of the endometrium is
      unfavorable but prompt detection with surgery and adjuvant therapy may confer a
      better clinical outcome.

PMID- 22949908
TI  - Neurological Adverse Effects after Radiation Therapy for Stage II Seminoma.
AB  - We report 3 cases of patients with testicular cancer and stage II seminoma who
      developed neurological symptoms with bilateral leg weakness about 4 to 9 months
      after radiation therapy (RT). They all received RT to the para-aortic lymph nodes
      with a total dose of 40 Gy (36 Gy + 4 Gy as a boost against the tumour bed) with
      a conventional fractionation of 2 Gy/day, 5 days per week. RT was applied as
      hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully
      resolved. Therapeutic irradiation can cause significant injury to the peripheral
      nerves of the lumbosacral plexus and/or to the spinal cord. RT is believed to
      produce plexus injury by both direct toxic effects and secondary microinfarction
      of the nerves, but the exact pathophysiology of RT-induced injury is unclear.
      Since reported studies of radiation-induced neurological adverse effects are
      limited, it is difficult to estimate their frequency and outcome. The treatment
      of neurological symptoms due to RT is symptomatic.

PMID- 22949909
TI  - Clear cell sarcoma: a case report with radiological and pathological features of
      an atypical case.
AB  - Clear cell sarcoma of soft tissue is a rare, aggressive soft tissue tumor, which
      is morphologically similar to malignant melanoma but has no precursor skin lesion
      and, instead, has a characteristic chromosomal translocation. It is critical, yet
      challenging, to recognize clear cell sarcoma of soft tissue because the outcome
      is very different to that of metastatic melanoma. We report a case of clear cell
      sarcoma of soft tissue arising in the left foot of a 35-year-old African-American
      woman.

PMID- 22949910
TI  - Transient global amnesia: a case report.
AB  - INTRODUCTION: Transient global amnesia is a syndrome of temporary and reversible
      disruption of short-term memory accompanied by repetitive questioning. Although
      the etiology is unknown, the prognosis usually benign, and no particular
      treatment is required, it is important for all involved clinicians to recognize
      the diagnosis and possess knowledge about the evaluation of these affected
      patients. CASE PRESENTATION: A middle-aged Caucasian woman presented for
      neurologic evaluation for acute forgetfulness. Neurologic examination disclosed
      repetitive questioning with preserved orientation and no focal motor, speech,
      sensory, coordination, or cranial nerve deficits. Neurologic investigations did
      not reveal any pathologic findings. Her memory improved and reverted to normal
      baseline over the course of a 24-hour hospital stay. CONCLUSION: Transient global
      amnesia is an interesting syndrome of reversible anterograde amnesia associated
      with repetitive questioning that occurs with an unclear etiology in middle-aged
      and elderly individuals. Due clinical diligence is required in the investigation
      of these patients. Treatment is generally not required, and the condition usually
      does not recur. Clinicians, including neurologists, internists, family practice
      physicians, and psychiatrists, need awareness of this condition.

PMID- 22949911
TI  - A patient with a prolonged activated partial thromboplastin time and a deep
      intracerebral haemorrhage.
AB  - We report on a 57-year-old woman with a pontine haemorrhage and an extremely
      prolonged activated partial thromboplastin time (aPTT) of more than 240 s,
      suggestive of a coagulation disorder. Given the location of the haemorrhage,
      which is associated with a high mortality rate, recombinant factor VIIa was
      administered, although not all necessary laboratory analyses could be performed
      at that time. In our case, a deficiency of factor XII was found, which is not
      associated with an increased bleeding risk. In an acute setting, evaluation of a
      prolonged aPTT may cause diagnostic and therapeutic challenges, in particular in
      situations where additional laboratory investigations may not be readily
      available.

PMID- 22949912
TI  - Pseudovitelliform Subfoveal Deposit in Waldenstrom's Macroglobulinemia.
AB  - BACKGROUND: Waldenstrom's macroglobulinemia may be complicated by retinal
      hemorrhages, retinal vein occlusion, serous macular detachment or macular edema.
      We report a patient with pseudovitelliform subfoveal deposit complicating
      Waldenstrom's macroglobulinemia. CASE REPORT: A 56-year-old man presented with
      hyperviscosity syndrome due to Waldenstrom's macroglobulinemia. After systemic
      therapy, a large serous retinal detachment persisted in the left eye. A
      pseudovitelliform subfoveal deposit was observed in the right eye. CONCLUSION:
      Pseudovitelliform subfoveal deposits may be part of the spectrum of ocular
      complications in Waldenstrom's macroglobulinemia. They could be due to
      accumulation of macroglobulins.

PMID- 22949913
TI  - Rapid regression of exudative maculopathy in idiopathic retinitis, vasculitis,
      aneurysms and neuroretinitis syndrome after intravitreal ranibizumab.
AB  - The idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome is a
      rare retinal vascular disorder characterized by multiple leaking aneurysmal
      dilations, retinal vasculitis, neuroretinitis and peripheral vascular ischemia.
      Visual loss mainly occurs due to the development of retinal neovascularization
      and/or exudative maculopathy. Although the treatment of choice has not yet been
      established, retinal photocoagulation seems to be the best option to control the
      disease and to prevent its progression. Herein, we report a case of idiopathic
      retinitis, vasculitis, aneurysms and neuroretinitis syndrome with both retinal
      neovascularization and macular exudation successfully managed with intravitreal
      ranibizumab (Lucentis((r))) as adjunctive therapy to retinal photocoagulation.

PMID- 22949914
TI  - Tissue plasminogen activator-assisted vitrectomy for ruptured eye with
      suprachoroidal hemorrhage.
AB  - PURPOSE: To report a case of a ruptured eye with a suprachoroidal hemorrhage
      (SCH) in which tissue plasminogen activator (tPA)-assisted vitrectomy was
      successful in reconstructing the globe and restoring good vision. CASE: A 32-year
      old man was struck on the right eye by a surfboard. His eye was ruptured and his
      visual acuity decreased to hand movements. Surgery was immediately performed to
      successfully close the ruptured globe. Nine days later, a second surgery was
      performed, and tPA (25 ug/0.1 ml monteplase) was used to liquefy and drain the
      SCH. This freed enough vitreous space for a more comprehensive vitrectomy.
      Eighteen months after the injury, the retina remained attached, and the decimal
      best-corrected visual acuity improved to 0.8. CONCLUSION: tPA was helpful in
      lysing a massive SCH, thereby contributing to the excellent visual outcome. tPA
      assisted drainage should be considered in cases of massive SCH when drainage is
      difficult due to an incomplete lysis of the clot.

PMID- 22949915
TI  - Cataractogenesis after Repeat Laser in situ Keratomileusis.
AB  - There has been the unsubstantiated clinical impression that laser refractive
      surgery accelerates cataract development along with solid experimental data about
      the cataractogenic effects of excimer laser treatment. We present the first
      documented case of significant cataract formation in a young myope after repeat
      excimer laser ablation necessitating phacoemulsification with a posterior chamber
      implant. Proposed explanations include focusing of the ablation wave on the
      posterior capsule (acoustic wave lens epithelial damage), photooxidative stress
      of the lens (ultraviolet and inflammatory oxidative stress), and corticosteroid
      induced cataract (lens toxicity).

PMID- 22949916
TI  - An unexpected delayed complication of cataract surgery: retinal detachment
      secondary to capsular tension ring dislocation.
AB  - We aim to present a case of retinal detachment secondary to capsular tension ring
      dislocation following cataract surgery. A 45-year-old man who underwent cataract
      surgery 2 years previously presented with decreased vision in his left eye. The
      patient's posterior capsule was intact with a well-located posterior chamber
      intraocular lens. Fundus examination revealed retinal detachment with retinal
      tears, and a capsular tension ring located around the tear was noticed during
      pars plana vitrectomy; it was removed through the sclerotomy site. In conclusion,
      dislocation of the capsular tension ring is a rare and unexpected complication of
      cataract surgery. Although the integrity of the posterior lens capsule is
      partially preserved, the ring may shift through a small tear in the bag even
      during its placement, and may cause retinal tears, retinal detachment or just
      remain silently suspended in the vitreous.

PMID- 22949917
TI  - Urinary matrix metalloproteinase activity in diabetic kidney disease: a potential
      marker of disease progression.
AB  - BACKGROUND: Progressive kidney fibrosis, associated with chronic kidney disease
      (CKD), results from an imbalance in extracellular matrix (ECM) homeostasis.
      Reduced matrix metalloproteinases (MMP) activity causing lower clearance of ECM
      proteins has been implicated mainly through an overproduction of tissue
      inhibitors of metalloproteinases (TIMP), but also by reduced MMP synthesis. We
      tested the hypothesis that MMP activity can be measured in human urine and can be
      used as a potential biomarker of the progression of diabetic kidney disease
      (DKD). METHODS: An observational prospective study was performed on 102 DKD
      patients using 21 diabetic patients without kidney disease and 21 healthy
      volunteers as controls. The Molecular Probes EnzChek Gelatinase/Collagenase Assay
      Kit were used to determine urinary MMP activity using DQTM Gelatin (total MMPs),
      DQTM Collagen I (interstitial collagenases) and DQTM Collagen IV (gelatinises)
      substrates. A broad-spectrum synthetic inhibitor of all MMP, 1,10-phenanthroline,
      was used to confirm that the proteolytic activity is due to MMP activity. All MMP
      values were expressed per unit of urine creatinine. RESULTS: Overall urinary MMP
      activity (DQ Gelatin substrate) was significantly elevated in DKD patients (14.76
      +/- 3.65 Delta fl/h/mmol creatinine) compared to diabetes mellitus controls (7.09
      +/- 2.12 Delta fl/h/mmol creatinine) and healthy volunteers (1.87 +/- 0.74 Delta
      fl/h/mmol creatinine) (ANOVA p = 0.01). Within the DKD cohort, there was an
      approximate threefold higher urinary MMP activity in nonprogressive DKD patients
      compared to those with progressive disease (p = 0.002). The urinary MMP
      activity:creatinine ratio was significantly higher in normoalbuminuric and
      microalbuminuric DKD compared to macroalbuminuric DKD. Positive correlations were
      observed between the rate of total MMP activity and interstitial collagenases (r
      = 0.75, p < 0.0001) and gelatinases (r = 0.59, p = 0.0001). The accuracy of MMP
      activity to predict the rate of annual eGFR decline (ROC analysis) was 77%
      compared to 64% for albuminuria. CONCLUSIONS: Total MMP activity can be easily
      measured in human urine. Surprisingly and in contrast to MMP activity in the
      kidney, urine MMP activity is elevated in DKD. However, there is a significantly
      lower MMP activity in patients with progressive DKD. ROC analysis demonstrates
      that single urine MMP activity estimation is superior to albuminuria in
      predicting DKD patients with progressive disease.

PMID- 22949918
TI  - Evolution and biological control.

PMID- 22949919
TI  - The biology of small, introduced populations, with special reference to
      biological control.
AB  - Populations are introduced into novel environments in different contexts, one
      being the biological control of pests. Despite intense efforts, less than half
      introduced biological control agents establish. Among the possible approaches to
      improve biological control, one is to better understand the processes that
      underpin introductions and contribute to ecological and evolutionary success. In
      this perspective, we first review the demographic and genetic processes at play
      in small populations, be they stochastic or deterministic. We discuss the
      theoretical outcomes of these different processes with respect to individual
      fitness, population growth rate, and establishment probability. Predicted
      outcomes differ subtly in some cases, but enough so that the evaluating results
      of introductions have the potential to reveal which processes play important
      roles in introduced populations. Second, we attempt to link the theory we have
      discussed with empirical data from biological control introductions. A main
      result is that there are few available data, but we nonetheless report on an
      increasing number of well-designed, theory-driven, experimental approaches.
      Combining demography and genetics from both theoretical and empirical
      perspectives highlights novel and exciting avenues for research on the biology of
      small, introduced populations, and great potential for improving both our
      understanding and practice of biological control.

PMID- 22949920
TI  - Sex determination meltdown upon biological control introduction of the parasitoid
      Cotesia rubecula?
AB  - Natural enemies may go through genetic bottlenecks during the process of
      biological control introductions. Such bottlenecks are expected to be
      particularly detrimental in parasitoid Hymenoptera that exhibit complementary sex
      determination (CSD). CSD is associated with a severe form of inbreeding
      depression because homozygosity at one or multiple sex loci leads to the
      production of diploid males that are typically unviable or sterile. We observed
      that diploid males occur at a relatively high rate (8-13% of diploid adults) in a
      field population of Cotesia rubecula in Minnesota, USA, where this parasitoid was
      introduced for biological control of the cabbage white Pieris rapae. However, our
      laboratory crosses suggest two-locus CSD in a native Dutch population of C.
      rubecula and moderately high diploid males survival (approximately 70%), a
      scenario expected to produce low proportions of diploid males. We also show that
      courtship behavior of diploid males is similar to that of haploid males, but
      females mated to diploid males produce only very few daughters that are triploid.
      We use our laboratory data to estimate sex allele diversity in the field
      population of C. rubecula and discuss the possibility of a sex determination
      meltdown from two-locus CSD to effective single-locus CSD during or after
      introduction.

PMID- 22949922
TI  - Host specificity in biological control: insights from opportunistic pathogens.
AB  - Host/prey specificity is a significant concern in biological control. It
      influences the effectiveness of a natural enemy and the risks it might have on
      non-target organisms. Furthermore, narrow host specificity can be a limiting
      factor for the commercialization of natural enemies. Given the great diversity in
      taxonomy and mode of action of natural enemies, host specificity is a highly
      variable biological trait. This variability can be illustrated by opportunist
      fungi from the genus Lecanicillium, which have the capacity to exploit a wide
      range of hosts - from arthropod pests to fungi causing plant diseases - through
      different modes of action. Processes determining evolutionary trajectories in
      host specificity are closely linked to the modes of action of the natural enemy.
      This hypothesis is supported by advances in fungal genomics concerning the
      identity of genes and biological traits that are required for the evolution of
      life history strategies and host range. Despite the significance of specificity,
      we still need to develop a conceptual framework for better understanding of the
      relationship between specialization and successful biological control. The
      emergence of opportunistic pathogens and the development of 'omic' technologies
      offer new opportunities to investigate evolutionary principles and applications
      of the specificity of biocontrol agents.

PMID- 22949921
TI  - Evolution and the microbial control of insects.
AB  - Insect pathogens can be utilized in a variety of pest management approaches, from
      inundative release to augmentation and classical biological control, and
      microevolution and the consideration of evolutionary principles can potentially
      influence the success of all these strategies. Considerable diversity exists in
      natural entomopathogen populations and this diversity can be either beneficial or
      detrimental for pest suppression, depending on the pathogen and its mode of
      competition, and this should be considered in the selection of isolates for
      biological control. Target hosts can exhibit considerable variation in their
      susceptibility to entomopathogens, and cases of field-evolved resistance have
      been documented for Bacillus thuringiensis and baculoviruses. Strong selection,
      limited pathogen diversity, reduced gene flow, and host plant chemistry are
      linked to cases of resistance and should be considered when developing resistance
      management strategies. Pre- and post-release monitoring of microbial control
      programs have received little attention; however, to date there have been no
      reports of host-range evolution or long-term negative effects on nontarget hosts.
      Comparative analyses of pathogen population structure, virulence, and host
      resistance over time are required to elucidate the evolutionary dynamics of
      microbial control systems.

PMID- 22949923
TI  - Evolution in biocontrol strains: insight from the harlequin ladybird Harmonia
      axyridis.
AB  - After being used as a biocontrol agent against aphids for decades without harmful
      consequences, the Asian harlequin ladybird Harmonia axyridis has suddenly become
      an invasive pest on a worldwide scale. We investigate the impact of captive
      breeding on several traits of this ladybird such as genetic diversity, fecundity,
      survival and pathogen resistance. We conducted an experiment in the laboratory to
      compare the fecundity and the susceptibility to the entomopathogenic fungus
      Beauveria bassiana of wild and biocontrol adults of H. axyridis. We compiled
      these new findings with already published data. Altogether, our findings suggest
      that mass rearing of biological control agents may strongly impact genetic
      diversity and life-history traits. We discuss how such changes may subsequently
      affect the fitness of biological control strains in natural environments.

PMID- 22949924
TI  - Hybrid vigor in the biological control agent, Longitarsus jacobaeae.
AB  - Hybridization is an important evolutionary mechanism that can increase the
      fitness and adaptive potential of populations. A growing body of evidence
      supports its importance as a key factor contributing to rapid evolution in
      invasive species, but the effects of hybridization have rarely been assessed in
      intentionally introduced biological control agents. We investigated hybrids
      between a Swiss and an Italian population of the beetle, Longitarsus jacobaeae, a
      biological control agent of Jacobaea vulgaris, by reciprocally crossing
      individuals in the laboratory. Phenological traits of F1 and F2 hybrid lineages
      showed intermediate values relative to their parental populations, with some
      maternal influence. Fitness of the F2 generation, measured as lifetime fecundity,
      was higher than that of the Italian parent in one of the lineages and higher than
      that of either parent in the other hybrid lineage. The increased fecundity of
      hybrids may benefit tansy ragwort biological control by increasing the
      establishment success and facilitating a more rapid population buildup in the
      early generations. Even though the long-term consequences of hybridization in
      this and other systems are hard to predict, intentional hybridization may be a
      useful tool in biological control strategies as it would promote similar
      microevolutionary processes operating in numerous targeted invasive species.

PMID- 22949925
TI  - Intraspecific variability in the parasitoid wasp Trichogramma chilonis: can we
      predict the outcome of hybridization?
AB  - In the framework of biological control, the selection of effective natural
      enemies determines the final pest control. Thus, the genetic improvement of
      biocontrol agents could enhance the efficiency of biocontrol programs. Although
      promising, this approach has rarely been applied in this field. At the
      intraspecific level, hybridization between divergent populations of biocontrol
      agents is expected to promote hybrid vigor (heterosis), but it is not clear to
      what extent. An even more difficult task is the ability to predict the fitness of
      hybrids from the biological characteristics of their parents. We investigated
      these general questions by crossing seven populations of the parasitoid wasp
      Trichogramma chilonis (Hymenoptera: Trichogrammatidae). Our results show
      different levels of mating compatibilities among populations, including
      asymmetric or almost complete reproductive isolation. Hybrids' performance
      (fitness of the F(1) generation) ranges from inbreeding depression to heterosis.
      It was possible, to some extent, to predict hybrid fitness from pairwise genetic
      and phenotypic distances among parents, in accordance with the 'dominance'
      hypothesis. This may provide general guidelines for the genetic improvement of
      biological control agents.

PMID- 22949926
TI  - Evolution of critical day length for diapause induction enables range expansion
      of Diorhabda carinulata, a biological control agent against tamarisk (Tamarix
      spp.).
AB  - In classical weed biological control, small collections of arthropods are made
      from one or a few sites in the native range of the target plant and are
      introduced to suppress the plant where it has become invasive, often across a
      wide geographic range. Ecological mismatches in the new range are likely, and
      success using the biocontrol agent may depend on postrelease evolution of
      beneficial life history traits. In this study, we measure the evolution of
      critical day length for diapause induction (day length at which 50% of the
      population enters dormancy), in a beetle (Diorhabda carinulata) introduced into
      North America from China to control an exotic shrub, Tamarix spp. Beetle
      populations were sampled from four sites in North America 7 years after
      introduction, and critical day length was shown to have declined, forming a cline
      over a latitudinal gradient At one field site, decreased critical day length was
      correlated with 16 additional days of reproductive activity, resulting in a
      closer match between beetle life history and the phenology of Tamarix. These
      findings indicate an enhanced efficacy and an increasingly wider range for D.
      carinulata in Tamarix control.

PMID- 22949927
TI  - Evolving while invading: rapid adaptive evolution in juvenile development time
      for a biological control organism colonizing a high-elevation environment.
AB  - We report evidence of adaptive evolution in juvenile development time on a
      decadal timescale for the cinnabar moth Tyria jacobaeae (Lepidoptera: Arctiidae)
      colonizing new habitats and hosts from the Willamette Valley to the Coast Range
      and Cascades Mountains in Oregon. Four lines of evidence reveal shorter egg to
      pupa juvenile development times evolved in the mountains, where cooler
      temperatures shorten the growing season: (i) field observations showed that the
      mountain populations have shorter phenological development; (ii) a common garden
      experiment revealed genetic determination of phenotypic differences in juvenile
      development time between Willamette Valley and mountain populations correlated
      with the growing season; (iii) a laboratory experiment rearing offspring from
      parental crosses within and between Willamette Valley and Cascades populations
      demonstrated polygenic inheritance, high heritability, and genetic determination
      of phenotypic differences in development times; and (iv) statistical tests that
      exclude random processes (founder effect, genetic drift) in favor of natural
      selection as explanations for observed differences in phenology. These results
      support the hypothesis that rapid adaptation to the cooler mountain climate
      occurred in populations established from populations in the warmer valley
      climate. Our findings should motivate regulators to require evaluation of
      evolutionary potential of candidate biological control organisms prior to
      release.

PMID- 22949928
TI  - Roles of computed tomography and [(18)F]fluorodeoxyglucose-positron emission
      tomography/computed tomography in the characterization of multiple solitary solid
      lung nodules.
AB  - The purpose of this study is to compare the performance of multidetector computed
      tomography (CT) and positron emission tomography/CT (PET/CT) with
      [(18)F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in
      14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were
      reviewed by a radiologist and nuclear medicine physician, respectively, blinded
      to the pathological diagnoses of lung cancer, considering nodule size, shape, and
      location (CT) and maximum standardized uptake value normalized to body weight
      (SUVbw max). Nodules were judged malignant or benign. The sensitivity,
      specificity, and accuracy of the two techniques were compared. CT had a
      sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively,
      whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and
      87.1%, respectively. Clinical management would have been erroneous in two
      patients by CT alone and in four patients by PET/CT alone. In one patient, the
      two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have
      complimentary roles in characterization of multiple solitary pulmonary nodules.
      Small nodules are poorly characterized by CT, and small-sized low-SUV malignant
      nodules are difficult to detect with PET/CT.

PMID- 22949929
TI  - Huge bilateral polycystic kidneys with suspicion of malignancy, recurrent
      bleeding in cysts, and acute abdomen.
AB  - We present a case of huge bilateral polycystic kidneys, with suspicion of
      malignancy and repeated admissions with acute abdomen, secondary to bleeding in
      cysts, and anaemia, requiring affected side nephrectomy. KEY MESSAGE: Autosomal
      dominant polycystic kidney disease (ADPKD) mostly ends up with end stage renal
      disease (ESRD), requiring haemodialysis, with increased risk of malignancy and
      enlargement of kidneys with its associated complications, mostly dealt with
      conservatively, except malignancy, which requires nephrectomy.

PMID- 22949930
TI  - Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms:
      implications for Alzheimer's disease.
AB  - Alzheimer's disease is characterized in part by extracellular aggregation of the
      amyloid-beta peptide in the form of diffuse and fibrillar plaques in the brain.
      Electron microscopy (EM) has made an important contribution in understanding of
      the structure of amyloid plaques in humans. Classical EM studies have revealed
      the architecture of the fibrillar core, characterized the progression of neuritic
      changes, and have identified the neurofibrillary tangles formed by paired helical
      filaments (PHF) in degenerating neurons. Clinical data has strongly correlated
      cognitive impairment in AD with the substantial synapse loss observed in these
      early ultrastructural studies. Animal models of AD-type brain amyloidosis have
      provided excellent opportunities to study amyloid and neuritic pathology in
      detail and establish the role of neurons and glia in plaque formation. Transgenic
      mice overexpressing mutant amyloid precursor protein (APP) alone with or without
      mutant presenilin 1 (PS1), have shown that brain amyloid plaque development and
      structure grossly recapitulate classical findings in humans. Transgenic APP/PS1
      mice expressing human apolioprotein E isoforms also develop amyloid plaque
      deposition. However no ultrastructural data has been reported for these animals.
      Here we show results from detailed EM analysis of amyloid plaques in APP/PS1 mice
      expressing human isoforms of ApoE and compare these findings with EM data in
      other transgenic models and in human AD. Our results show that similar to other
      transgenic animals, APP/PS1 mice expressing human ApoE isoforms share all major
      cellular and subcellular degenerative features and highlight the identity of the
      cellular elements involved in Abeta deposition and neuronal degeneration.

PMID- 22949931
TI  - Predictors of Gleason Score (GS) upgrading on subsequent prostatectomy: a single
      Institution study in a cohort of patients with GS 6.
AB  - BACKGROUND: Biopsy Gleason score (bGS) remains an important prognostic indicator
      for adverse outcomes in Prostate Cancer (PCA). In the light of recent studies
      purporting difference in prognostic outcomes for the subgroups of GS7 group
      (primary Gleason pattern 4 vs. 3), upgrading of a bGS of 6 to a GS>=7 has serious
      implications. We sought to identify pre-operative factors associated with
      upgrading in a cohort of GS6 patients who underwent prostatectomy. DESIGN: We
      identified 281 cases of GS6 PCA on biopsy with subsequent prostatectomies. Using
      data on pre-operative variables (age, PSA, biopsy pathology parameters), logistic
      regression models (LRM) were developed to identify factors that could be used to
      predict upgrading to GS>=7 on subsequent prostatectomy. A decision tree (DT) was
      constructed. RESULTS: 92 of 281 cases (32.7%) were upgraded on subsequent
      prostatectomy. LRM identified a model with two variables with statistically
      significant ability to predict upgrading, including pre-biopsy PSA (Odds Ratio
      8.66; 2.03-37.49, 95% CI) and highest percentage of cancer at any single biopsy
      site (Odds Ratio 1.03, 1.01-1.05, 95% CI). This two-parameter model yielded an
      area under curve of 0.67. The decision tree was constructed using only 3 leave
      nodes; with a test set classification accuracy of 70%. CONCLUSIONS: A simplistic
      model using clinical and biopsy data is able to predict the likelihood of
      upgrading of GS with an acceptable level of certainty. External validation of
      these findings along with development of a nomogram will aid in better
      stratifying the cohort of low risk patients as based on the GS.

PMID- 22949932
TI  - Morphoproteomics provides support for TGF-beta pathway signaling in the
      osteoclastogenesis and immune dysregulation of osteolytic Langerhans cell
      histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) has a challenging and still unclear
      pathogenesis. A body of literature points to impaired maturation of the lesional
      dendritic cells, and to immune dysregulation in the form of increased FoxP3
      cells. Various cytokine abnormalities such as expression of transforming growth
      factor (TGF)-beta have been reported, as well as abnormalities in lipid content
      in LCH cells. Morphoproteomic techniques were applied to identify the signal
      transduction pathways that could influence histogenesis and immune regulation in
      osteolytic LCH. Five pediatric cases of osteolytic LCH were examined, using
      antibodies against CD1a, S100, CD68, CD8, FoxP3, phosphorylated (p)-STAT3
      (Tyr705), protein kinase C (PKC)-alpha, phospholipase (PL)D1, fatty acid synthase
      (FASN), and zinc finger protein, Gli2. Positive and negative controls were
      performed. A FoxP3(+)/CD8(+) cell ratio was calculated by counting the FoxP3+ and
      CD8+ cells in 10 high power fields for each case. There is induction of sonic
      hedgehog (SHH) mediators consistent with TGF-beta signaling pathway through Smad3
      dependent activation of Gli2, findings supported by the plasmalemmal and
      cytoplasmic expression of PKC-alpha and PLD1, and nuclear expression of Gli2, in
      lesional cells. The FoxP3+/CD8+ cell ratio is increased, ranging from 1.7-7.94.
      There is moderate cytoplasmic expression of FASN in most of the Langerhans cells,
      a finding that supports previously published phospholipid abnormalities in LCH
      and is consistent with PKC-alpha/PLD1/TGF-beta signaling. With our study, we
      strongly suggest that the TGF-beta cell signaling pathway is a major player in
      the pathogenesis of LCH, leading to non-canonical induction of nuclear Gli2
      expression, thereby contributing to osteoclastogenesis in LCH histiocytes. It
      could also cause a state of immune frustration in LCH, by inducing the
      transformation of CD4(+)CD25(-) cells into CD4(+)/FoxP3(+) cells. This coincides
      with the clinical evidence of a response to thalidomide in patients with
      osteolytic LCH, given its reported ability to reduce TGF-beta 1 and FoxP3 cells.
      Such TGF-beta signaling in osteoclastogenesis and immune dysregulation, and the
      presence of FASN in the majority of cells, have additional therapeutic
      implications for osteolytic LCH.

PMID- 22949933
TI  - Hepatic angiomyolipoma: a series of six cases with emphasis on pathological
      radiological correlations and unusual variants diagnosed by core needle biopsy.
AB  - Hepatic angiomyolipoma is rare and may pose differential diagnostic difficulty,
      particularly if encountered in core needle biopsy. We studied 6 cases from 5
      males and one female (median age, 48.6 yrs). All presented with non-specific
      symptoms or an incidentally discovered tumor mass. Two patients had a remote
      history of chemotherapy for hematological neoplasms (acute lymphoblastic leukemia
      and Hodgkin lymphoma respectively) and another had clear cell renal cell
      carcinoma and anaplastic pancreatic carcinoma diagnosed at autopsy without
      definable syndrome. None of the patients had evidence of the tuberous sclerosis
      complex or renal or other extra-renal angiomyolipoma. Three tumors were resected
      completely and three have been only biopsied and followed up. None of the
      resected cases recurred at a mean follow-up of 35 months. Histologically, tumors
      were classified as classical triphasic (1), lipomatous (2),
      epithelioid/oncocytoid (1), epithelioid trabecular (1) and myelolipoma-like (1).
      The adjacent liver parenchyma was normal in 3 cases, showed pigment cirrhosis in
      one case and mild fatty change in another case. One case had clinically diagnosed
      but histologically unverified cirrhosis. The initial diagnostic impression/frozen
      section was misleading in 5 of the cases and included vascular lesion, focal
      fatty change, myelolipoma, hepatocellular tumor and oncocytic neoplasm. All
      tumors expressed HMB45 and variably desmin. One epithelioid lesion expressed
      HMB45 and TFE3, but lacked desmin expression. In conclusion, hepatic
      angiomyolipomas are increasingly recognized as incidental findings during
      surveillance for cirrhosis or investigations for unrelated conditions. Awareness
      of their diverse morphological spectrum in liver biopsy is necessary to avoid
      misdiagnosis as hepatocellular carcinoma, metastatic melanoma or other malignant
      neoplasms.

PMID- 22949934
TI  - Telmisartan counteracts TGF-beta1 induced epithelial-to-mesenchymal transition
      via PPAR-gamma in human proximal tubule epithelial cells.
AB  - Chronic renal failure (CRF) mainly results from kidney fibrosis. Epithelial-to
      mesenchymal transition (EMT) occurs in stressed tubular epithelial cells and
      contributes to renal fibrosis. Transforming growth factor-beta1 (TGF-beta1) has
      been shown to initiate and complete the whole EMT process. Peroxisome
      proliferators-activated receptor-gamma (PPAR-gamma) exerts anti-inflammatory,
      anti-fibrotic and vaculo-protective effects on different renal diseases.
      Telmisartan is a member of angiotensin II (Ang II) receptor blocker (ARB) family.
      Recent studies show that Telmisartan has a partial agonistic effect on PPAR
      gamma. Therefore, we tested the hypothesis that Telmisartan reverses the
      progression of induced EMT by TGF-beta1 in cultured human renal proximal tubular
      epithelial (HK-2) cells. Cultured HK-2 cells were treated with TGF-beta1 (3
      ng/ml), a combination of TGF-beta1 and Telmisartan (10-200 umol/L) and a
      combination of TGF-beta1, Telmisartan and GW9662, a PPAR-gamma antagonist for 48
      hours. EMT was determined by quantitative real-time PCR analysis of E-cadherin (E
      cad), Connective Tissue Growth Factor (CTGF) and PPAR-gamma transcript expression
      and immunocytochemical analysis of E-cad, alpha-Smooth Muscle Actin (alpha-SMA)
      and PPAR-gamma protein expression. TGF-beta1 induced phenotypic EMT in cultured
      HK-2 cell line via significantly reduced E-cad expression and significantly
      increased CTGF, alpha-SMA expression in association with the loss of epithelial
      morphology. Telmisartan reversed all EMT markers in a dose-dependent manner which
      was inhibited by PPAR antagonist GW9662. In the present study, it was suggested
      that Telmisartan attenuated TGF-beta1 induced EMT by agonistic activation of PPAR
      gamma.

PMID- 22949935
TI  - Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression pre- and
      post- neoadjuvant chemotherapy in primary breast carcinoma: a single
      institutional experience.
AB  - BACKGROUND: The estrogen receptor (ER), progesterone receptor (PR), and HER2
      profile of a primary breast carcinoma plays a significant role in patient
      management and treatment. Because of the increasing utilization of neoadjuvant
      chemotherapy or hormone therapy, surgically-resected carcinomas often show marked
      treatment effect. The aim of this study was to compare immunohistochemical (IHC)
      profiles (ER, PR, HER2, HER2 FISH) of primary breast carcinomas before and after
      neoadjuvant chemotherapy to assess the subsequent effects on hormone receptor
      status. DESIGN: Primary breast carcinomas from 38 female patients treated with
      neoadjuvant therapy after needle core biopsy or fine needle aspiration diagnosis
      were included. Histologic data was collected for each case, including site, type,
      grade, tumor size (cm), pre- and post- neoadjuvant treatment IHC panel (ER, PR,
      HER2), and fluorescence in-situ hybridization (FISH) for HER2. RESULTS: Of the 38
      carcinomas studied, 45 % were positive for ER by IHC both pre- and post-
      neoadjuvant treatment (P=1.00). IHC studies for PR in these 38 patients showed
      37% positivity for PR pre-neoadjuvant therapy and 21% positivity post-treatment
      (p=0.03). For 37 patients with HER2 IHC, 32% were positive pre-treatment, and 22%
      were positive post-treatment (P = 0.20). For 7 patients, HER2 FISH was positive
      in 71% pre-therapy and in 57% post-treatment (P=0.32). CONCLUSIONS: Profiles for
      ER, HER2 IHC, and HER2 FISH were not significantly different in primary breast
      carcinomas before and after neoadjuvant chemotherapy. Further investigation is
      warranted to assess reproducibility of technique and investigate clinical
      implications of significant loss of PR status in treated patients.

PMID- 22949936
TI  - Analysis of whole genomic expression profiles and screening of the key signaling
      pathways associated with pancreatic cancer.
AB  - The tumorigenesis of pancreatic cancer is thought to be a complex process.
      Investigation of the molecular mechanism of pancreatic cancer and exploring the
      specific markers for early diagnosis and specific targets of therapy is a key
      point to prevent and treat pancreatic cancer effectively and to improve their
      prognosis. In this study, expression profiles experiment was performed using
      Agilent human whole genomic oligonucleotide microarrays with 41,000 genes.
      Differentially expressed genes related with pancreatic cancer were screened, and
      analyzed further by GO term analysis and KEGG Pathway analysis. Our results
      showed that there were 1276 differentially expressed genes associated with
      pancreatic cancer. 691 genes were up regulated and 585 were down regulated in
      pancreatic cancer group. The present study confirmed that the occurrence of
      pancreatic cancer was involved in multiple-gene interaction. In addition, our
      study found that pancreatic cancer was related to an activation of the mTOR
      signaling pathway and renal cell carcinoma pathway.

PMID- 22949937
TI  - The inactive form of glycogen synthase kinase-3beta is associated with the
      development of carcinomas in galectin-3 wild-type mice, but not in galectin-3
      deficient mice.
AB  - Galectin-3 has been implicated in the tumor development via its mediation of the
      Wnt signaling pathway. Likewise, glycogen synthase kinase-3beta (GSK3beta) also
      plays a role in the Wnt signaling pathway by controlling the levels of
      cytoplasmic beta-catenin. Altered GSK3beta expression has been described in
      various tumors, but to date, there are no studies evaluating its expression in
      models of oral carcinogenesis. Additionally, it is unknown whether the absence of
      galectin-3 regulates the expression of GSK3beta. To this end, Gal3-deficient
      (Gal3(-/-)) and wild-type (Gal3(+/+)) male mice were treated with 4NQO for 16
      weeks and sacrificed at week 16 and 32. The tongues were removed, processed, and
      stained with H&E to detect dysplasias and carcinomas. An immunohistochemical
      assay was performed to determine the level of P-GSK3beta-Ser9 expression in both
      groups. Carcinomas were more prevalent in Gal3(+/+) than Gal3(-/-) mice (55.5%
      vs. 28.5%), but no statistical difference was reached. In the dysplasias, the
      proportion of cells positive for P-GSK3beta-Ser9 was slightly higher in Gal3(+/+)
      than Gal3(-/-) mice (63% vs. 61%). In the carcinomas, a significant difference
      between Gal3(+/+) and Gal3(-/-) mice was found (74% vs. 59%; p=0.02). P-GSK3beta
      Ser9-positive cells slightly decreased from the progression of dysplasias to
      carcinomas in Gal3(-/-) mice (61% vs. 59%; p>0.05). However, a significant
      increase in P-GSK3beta-Ser9 expression was observed from dysplasias to carcinomas
      in Gal3(+/+) mice (63% vs. 74%; p=0.01). In conclusion, these findings suggest
      that fully malignant transformation of the tongue epithelium is associated with
      increased P-GSK3beta-Ser9 expression in Gal3(+/+) mice, but not in Gal3(-/-)
      mice.

PMID- 22949938
TI  - Knockdown of apoptosis repressor with caspase recruitment domain (ARC) increases
      the sensitivity of human glioma cell line U251MG to VM-26.
AB  - Previous studies have demonstrated that apoptosis repressor with caspase
      recruitment domain (ARC) is up-regulated in many forms of malignant tumors and
      low levels of ARC protein were expressed in normal human brain tissue. Little is
      known expression of ARC in glioma. Here, we found that ARC protein was highly
      expressed in primary human glioma when compared with normal brain tissues. A
      decrease in cell viability and an increase in apoptosis were observed in U251MG
      cells after ARC was knocked down. Knockdown of ARC was confirmed by western
      blotting. Knockdown of ARC promoted caspase-8, caspase-3 activation and Bax
      accumulation. These results indicate that ARC has a anti-apoptosis function in
      glioma.

PMID- 22949939
TI  - The cell death of C6 astrocytoma cells induced by oridonin and its mechanism.
AB  - Many studies have shown that oridonin, a compound purified from Rabdosia
      rubescens, was able to suppress proliferation and induce apoptosis in many cell
      types. In this study, In order to investigate the proliferation suppression and
      apoptosis-inducing effect of oridonin on Rat C6 astrocytoma cells, we treated C6
      cells with different concentrations of oridonin for various time intervals.
      Oridonin concentration-time viability curve were used to test the effect of
      oridonin on the C6 cells. The distribution of cell cycle and percentage of
      apoptosis cells was analyzed by flow cytometry. The protein expression of Bax,
      Bcl-2, and caspase-3 in the C6 cells was detected by western blot analysis. The
      results of viability curve demonstrated that oridonin induced suppression of
      proliferation in a concentration- and time-dependent manner. Hochest 33258
      staining and flow cytometry revealed that oridonin induced apoptosis and arrested
      the entry into G2/M phase of C6 cells. According to the results of Western blot,
      oridonin down-regulated Bcl-2, up-regulated Bax protein, and activated caspase-3
      in the oridonin-treated C6 cells. All together, our results suggested that
      oridonin can cause the suppression of proliferation in C6 astrocytoma cells and
      the cell death induced by oridonin might be associated with mitochondria-
      mediated apoptosis by activating caspase-3.

PMID- 22949940
TI  - Keratinocyte growth factor up-regulates Interleukin-7 expression following
      intestinal ischemia/reperfusion in vitro and in vivo.
AB  - BACKGROUND: Epithelial cell (EC)-derived Interleukin-7 (IL-7) plays a crucial
      role in control of neighboring intestinal intraepithelial lymphocytes (IEL)
      development and homeostasis, and IEL derived keratinocyte growth factor (KGF)
      promotes intestinal epithelial growth, which was regulated by EC-derived IL-7. On
      this basis, we hypothesize that there is a crosstalk between IELs and ECs, and
      KGF could regulate the EC-derived IL-7 expression, which should be associated
      with the protective effects by KGF on intestinal injury. METHODS: Histological
      evaluation was performed in small intestine tissues of patients with intestinal
      obstruction and IL-7 expression was detected by immunofluorescence. Intestinal
      epithelial cells (LoVo) and adult C57BL/6J mice undergoing ischemia/reperfusion
      injury were treated with recombinant KGF. KGF, KGF receptor(KGFR) and IL-7
      expressions were measured with western blot and immunofluorescence analysis.
      RESULTS: IL-7 expression increased in the mild ischemia while decreased in severe
      ischemia small intestinal tissues of patients with intestinal obstruction. KGF
      expression significantly decreased while IL-7 expression increased early after
      acute intestinal I/R administration in a mouse model. KGF treatment significantly
      increased the IL-7 expression both in vitro and in vivo, while when the KGFR was
      blocked, the findings above were absent. In addition, our results showed changes
      of IL-7 expression at different stages after acute intestinal I/R administration,
      KGF treatment significantly attenuated the decreasing of IL-7 expression caused
      by acute intestinal I/R. CONCLUSION: KGF could up-regulate the IL-7 expression
      both in vitro and in vivo through KGFR pathway, which should have associated with
      the protective effects of KGF in intestinal injury.

PMID- 22949941
TI  - An examination of the relationship between the endoscopic appearance of
      duodenitis and the histological findings in patients with epigastric pain.
AB  - The endoscopic appearance of duodenitis is a common finding in patients
      undergoing endoscopy because of epigastric pain however, the relationship of the
      visual findings to histology is poorly defined. We set out to ascertain if there
      was a correlation between the endoscopic and histological appearances of the
      duodenal mucosa. Consecutive patients with epigastric pain referred for
      diagnostic gastroduodenoscopy were studied. The visual appearances of
      'duodenitis' (erythema, erosions and sub-epithelial haemorrhage) were reported
      independently by two endoscopists. Duodenal biopsies were taken and assessed for:
      neutrophil infiltrate, mononuclear infiltrate, gastric metaplasia, villous
      atrophy and a breach in the mucosa. H pylori status was determined. Of the 93
      patients with endoscopic features of duodenitis an increase in histological
      markers of inflammation was found in 75 (81%). However, histological inflammation
      was absent or minimal in 68 (73%). Conversely, biopsies from normal-looking
      mucosa revealed histological evidence of inflammation in 26 (27%). For patients
      with the endoscopic features of duodenitis the positive & negative predictive
      value for neutrophilic infiltrate was 39% and 98% respectively. Biopsies from
      erosions confirmed a breach in the mucosa in only 2 of 40 patients. Neutrophilic
      infiltrate occurred with NSAI ingestion and infection with H pylori. The
      endoscopic appearance of the duodenal mucosa is unreliable in determining the
      presence of histological inflammation. The endoscopic appearance of 'erosions' is
      not usually associated with a mucosal breach.

PMID- 22949942
TI  - Renal cell carcinoma metastatic to the nasal cavity.
AB  - Metastatic renal cell carcinoma of the nasal cavity is very rare. A 76-year-old
      man presented with epistaxis and admitted to our hospital. His past histories
      were right radical nephrectomy for renal cell carcinomas at the age of 68 years
      and brain infarction at the age of 75 years. Laryngoscopic examination revealed a
      red polyp of the right nasal cavity. Imaging modalities including CT and MRI also
      revealed a tumor measuring 2 x 3 x 2 cm. Angiography showed that the tumor is
      very hypervascular. Clinical diagnosis was angiogenic tumors including
      hemangioma, sinonasal hemangiopericytoma, and paraganglioma. A blood data showed
      anemia and low platerets, and bone marrow biopsy revealed myelodysplastic
      syndrome. A coiling embolization of the feeding artery was performed, and the
      tumor reduced markedly. The tumor was resected almost entirely. Pathologically,
      the tumor was 2 x 1.5 x 1.5 cm red tumor. The tumor cells had clear cytoplasm,
      and arranged in a trabecular pattern lined by a layer of endothelial cells.
      Atypia is mild. Immunohistochemically, the tumor cells were positive for
      pancytokeratin (AE1/3, CAM5.2), RCC ma, CD10, and Ki-67 (labeling=20%), but
      negative for CD34, factor-VIII-related antigen, CEA, EMA, melanosome (HMB45),
      S100 protein, p53, and HepPar-1. The pathological diagnosis was made without
      knowledge of kidney status. A pathological diagnosis of metastatic renal cell
      carcinoma of clear cell type (grade 1) was made. The patient is now free from
      tumor, and palliative chemoradiation is considered.

PMID- 22949943
TI  - Concurrent Paget's disease and basal cell carcinoma of the vulva; a case report.
AB  - An 82-year-old Caucasian woman had a long-standing history of recurrent Paget's
      disease of the right perianal region that was documented by multiple skin
      biopsies. Histological examination of a skin biopsy from an erythematous raised
      right perianal area revealed large rounded cells with ample pale staining
      cytoplasm scattered throughout the epidermis in multifocal nests and a flattened
      basal layer. A second lesion showed tongues of basaloid cells with peripheral
      palisading in continuity with the undersurface of the epidermis at multiple
      points. The individual tumor nests had cytoplasmic melanization and slit-like
      stromal separation. The tumor cells in the epidermis showed positive
      immunoreactivity for carcinoembryonic antigen while the basaloid cells were
      negative. A diagnosis of combined vulvar Paget's disease and basal cell carcinoma
      of an infundibulocystic type was rendered. Concurrent involvement of the same
      area by Paget's disease and Basal cell carcinoma (BCC) has been reported only
      once. Here we report a second case of BCC concurrent with vulvar Paget's disease.

PMID- 22949944
TI  - Small cell carcinoma of the urinary bladder.
AB  - Primary small cell carcinoma of the urinary bladder is very rare; only several
      studies have been reported in the English literature. A 62-year-old woman was
      admitted to our hospital because of hematuria and dysuria. Bladder endoscopy
      revealed a large polypoid tumor at the bladder base. Transurethral bladder
      tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained.
      Histologically, the bladder tumor was pure small cell carcinoma.
      Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3,
      CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56),
      synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived
      growth factor receptor-alpha (PDGFRA). The tumor cells were negative for CK5/6,
      CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic
      analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13
      and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various
      imaging techniques. The patient is now treated by cisplatin-based chemotherapy.

PMID- 22949945
TI  - Plasmacytoid urothelial carcinoma of the urinary bladder: a clinical pathological
      study and literature review.
AB  - PURPOSE: Plasmacytoid carcinoma of the urinary bladder or plasmacytoid urothelial
      carcinoma (PUC) is a rare and only recently described histological variant of
      transitional cell carcinoma (TCC). We herein report the clinical and
      histopathological features for a new case of PUC. By combining with those
      reported cases, we intend to define the characteristics of PUC and to provide a
      therapeutic and prognostic guidance for this disease. MATERIALS AND METHODS: The
      index case at our institution was a patient with complaint of lower abdominal
      pain but without any urological symptoms. The patient underwent radical
      cystectomy, and the representative sections of tumor were submitted for
      immunohistochemical analysis. The data for this patient were collected from
      clinical charts, histological review and follow-up studies. We also performed an
      extensive literature review of PUC including clinical presentation, pathological
      features, therapy and prognosis. RESULTS: Clinically, patients with PUC are
      associated with nonspecific abdominal pain but absent of hematuria. Cystoscopy
      analysis revealed that PUC is manifested by the coarse and indurated mucosal
      fold. Macroscopic studies demonstrated an ulcerated firm mass which was present
      in the left lateral wall of the bladder. Histologically, PUC appeared to be
      dyscohesive, plasmacytoid cells with eccentric nuclei and abundant eosinophilic
      cytoplasm with characteristics of plasmacytoid morphology. The tumor cells are
      negative for E-cadherin, but positive for CD138 expression. This particular
      patient died 3 months after the radical cystectomy and one course of adjuvant
      chemotherapy. Literature review revealed that most PUC cases showed similar
      clinical and pathological features along with poor prognosis. CONCLUSIONS: PUC is
      a rare tumor associated with poor prognosis due to its advanced clinical stage
      upon its diagnosis. The delayed diagnosis is mainly due to the late occurrence of
      hematuria and absence of papulary mucosal surface at cystoscopy. Diagnosis can be
      achieved based on its typical histological features, clinical history and
      immunohistochemical results. Other than radical cystectomy, postoperative
      adjuvant treatment could be a good approach to prolong the survival time of PUC
      patients.

PMID- 22949946
TI  - Late recurrence of sigmoid carcinoma mimicking primary vulvar cancer: case report
      and review of the literature.
AB  - OBJECTIVE: To demonstrate a unique case report about late and isolated vulvar
      metastasis of sigmoid adeno-carcinoma with review of the literature. MATERIAL
      METHOD: 57 year old postmenopausal patient with prior sigmoid colon cancer
      history was admitted with isolated vulvar mass. Immunohistochemistry (IHC) and
      KRAS gen mutation analysis following surgery were performed to discriminate the
      metastasis from a vulvar primary malignancy. Further imaging techniques were also
      performed to exclude additional tumours. RESULTS: Immunohistochemistry (IHC) and
      KRAS gene mutation analysis revealed isolated metastasis of the colonic adeno
      carcinoma in the vulva. CONCLUSION: Isolated and late occurring vulvar metastasis
      of colonic origin is very unusual. Careful evaluation and IHC is useful for such
      cases.

PMID- 22949947
TI  - Subchondral insufficiency fractures of the femoral head.
AB  - A subchondral insufficiency fracture (SIF) of the femoral head is a recently
      proposed concept, which needs to be differentiated from osteonecrosis.
      Clinically, SIF has generally been observed in the osteoporotic elderly women or
      renal transplant recipients. Radiographical changes are not obvious in its early
      phase, however, some cases undergo subchondral collapse (crescent sign). On the
      T1-weighted magnetic resonance images, a low intensity band is one of the
      characteristic imaging appearances, which corresponds histologically to the
      fracture line and associated fracture repair tissue. Therefore, the shape of the
      low intensity band generally tends to be irregular, disconnected, and convex to
      the articular surface. The prognosis of SIF is not clearly established. Some
      cases show resolution of the symptoms by the conservative treatments, while other
      cases show rapid progression of the collapse such as rapidly progressive
      arthrosis of the hip.

PMID- 22949948
TI  - Minocycline-induced periarticular black bones in inflamed joints which underwent
      arthroplastic reconstruction.
AB  - BACKGROUND: Minocycline-induced pigmentation of bone (black bone) is well
      described in tooth-bearing intra-oral bone, but is less known in periarticular
      bone in patients who have undergone total joint arthroplasty. On a retrospective
      basis, we investigated the short-term clinico-radiological results of total joint
      arthroplasties in which the patient developed minocycline-induced periarticular
      black bone. METHODS: We found 5 cases (0.08%), in 4 patients, of periarticular
      bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees,
      and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year
      time period in our 3 institutes. Their mean age was 56 years at surgery. All
      patients had received long-term minocycline treatment. Mean dosage and duration
      of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been
      prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late
      infection after total joint arthroplasty (two patients). Mean follow-up period
      was 3.4 years after the surgeries. RESULTS: All cases had black or brown
      pigmentation in the periarticular bones during the surgery. There was no
      pigmentation in the cartilage or soft tissues of the joints. The mean Japanese
      Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot
      (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up
      (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to
      those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5,
      55). No implant loosening was noted on radiographic examination during the follow
      up period. No abnormal bone formation, bone necrosis, hemosiderin deposition,
      malignancy or metallic debris was found on histological examination. CONCLUSIONS:
      No clinico-radiological symptoms of total joint arthroplasties showed in the
      patients with minocycline-induced periarticular black bone in the short-term.
      Systemic minocycline treatment has the potential to induce significant black
      pigmentation of many tissues. In particular, minocycline-induced pigmentation of
      periarticular bone may be accelerated by inflammation due to rheumatic or
      pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in
      inflamed joints due to the systemic treatment of minocycline and explore its
      influence on periarticular bone and total joint arthroplasty in the long-term.

PMID- 22949949
TI  - Development of a pneumatic tensioning device for gap measurement during total
      knee arthroplasty.
AB  - BACKGROUND: Despite the importance of soft tissue balancing during total knee
      arthroplasty (TKA), all estimating techniques are dependent on a surgeon's manual
      distraction force or subjective feeling based on experience. We developed a new
      device for dynamic gap balancing, which can offer constant load to the gap
      between the femur and tibia, using pneumatic pressure during range of motion.
      METHODS: To determine the amount of distraction force for the new device, 3
      experienced surgeons' manual distraction force was measured using a conventional
      spreader. A new device called the consistent load pneumatic tensor was developed
      on the basis of the biomechanical tests. Reliability testing for the new device
      was performed using 5 cadaveric knees by the same surgeons. Intraclass
      correlation coefficients (ICCs) were calculated. RESULTS: The distraction force
      applied to the new pneumatic tensioning device was determined to be 150 N. The
      interobserver reliability was very good for the newly tested spreader device with
      ICCs between 0.828 and 0.881. CONCLUSIONS: The new pneumatic tensioning device
      can enable us to properly evaluate the soft tissue balance throughout the range
      of motion during TKA with acceptable reproducibility.

PMID- 22949950
TI  - Three dimensional CT-based virtual patellar resection in female patients
      undergoing total knee replacement: a comparison between tendon and subchondral
      method.
AB  - BACKGROUND: Due to its small size, variable shape, and lack of distinct
      anatomical landmarks, osteoarthritic knees make a precise patellar resection
      extremely difficult. METHODS: We performed virtual patellar resection with
      digital software using three dimensional computed tomography scans of knees from
      49 patients who underwent primary total knee replacement at our hospital. We
      compared 2 commonly used resection methods, the tendon method (TM) and the
      subchondral method, to determine an ideal resection plane with respect to the
      symmetry and thickness of the patellar remnant. RESULTS: The TM gave a thicker
      resected patella, and a less oval cut surface shape, which gives better coverage
      for a domed prosthesis. Both methods, however, gave a symmetric resection both
      superior-inferiorly, as well as mediolaterally. CONCLUSIONS: Although TM appears
      statistically better with respect to the thickness and cut surface shape, only
      further intraoperative studies with long-term clinical follow-up may provide us
      with the most appropriate patellar resection method.

PMID- 22949951
TI  - Transpedicular curettage and drainage of infective lumbar spondylodiscitis:
      technique and clinical results.
AB  - BACKGROUND: Infective spondylodiscitis usually occurs in patients of older age,
      immunocompromisation, co-morbidity, and individuals suffering from an overall
      poor general condition unable to undergo reconstructive anterior and posterior
      surgeries. Therefore, an alternative, less aggressive surgical method is needed
      for these select cases of infective spondylodiscitis. This retrospective clinical
      case series reports our novel surgical technique for the treatment of infective
      spondylodiscitis. METHODS: Between January 2005 and July 2011, among 48 patients
      who were diagnosed with pyogenic lumbar spondylodiscitis or tuberculosis lumbar
      spondylodiscitis, 10 patients (7 males and 3 females; 68 years and 48 to 78
      years, respectively) underwent transpedicular curettage and drainage. The mean
      postoperative follow-up period was 29 months (range, 7 to 61 months). The pedicle
      screws were inserted to the adjacent healthy vertebrae in the usual manner. After
      insertion of pedicle screws, the drainage pedicle holes were made through
      pedicles of infected vertebra(e) in order to prevent possible seeding of
      infective emboli to the healthy vertebra, as the same instruments and utensils
      are used for both pedicle screws and the drainage holes. A minimum of 15,000 mL
      of sterilized normal saline was used for continuous irrigation through the
      pedicular pathways until the drained fluid looked clear. RESULTS: All patients'
      symptoms and inflammatory markers significantly improved clinically between
      postoperative 2 weeks and postoperative 3 months, and they were satisfied with
      their clinical results. Radiologically, all patients reached the spontaneous
      fusion between infected vertebrae and 3 patients had the screw pulled-out but
      they were clinically tolerable. CONCLUSIONS: We suggest that our method of
      transpedicular curettage and drainage is a useful technique in regards to the
      treatment of infectious spondylodiscitic patients, who could not tolerate
      conventional combined anterior and posterior surgery due to multiple co
      morbidities, multiple level infectious lesions and poor general condition.

PMID- 22949952
TI  - Locking plate for proximal humeral fracture in the elderly population: serial
      change of neck shaft angle.
AB  - BACKGROUND: We conducted this radiographic study in the elderly population with
      proximal humeral fracture aiming to evaluate 1) the serial changes of neck-shaft
      angle after locking plate fixation and 2) find relationship between change in
      neck shaft angle and various factors such as age, fracture pattern, severity of
      osteoporosis, medial support and initial reduction angle. METHODS: Twenty-five
      patients who underwent surgical treatment for proximal humeral fracture with
      locking plate between September 2008 and August 2010 are included. True
      anteroposterior and axillary lateral radiographs were made postoperatively and at
      each follow-up visit. Measurement of neck shaft angle was done at immediate
      postoperative, 3 months postoperative and a final follow-up (average, 11 months;
      range, 8 to 17 months). Severity of osteoporosis was assessed using cortical
      thickness suggested by Tingart et al. RESULTS: The mean neck shaft angles were
      133.6 degrees  (range, 100 degrees  to 116 degrees ) at immediate postoperative,
      129.8 degrees  (range, 99 degrees  to 150 degrees ) at 3 months postoperative and
      128.4 degrees  (range, 97 degrees  to 145 degrees ) at final follow-up. The mean
      loss in the neck-shaft angle in the first 3 months was 3.8 degrees  as compared
      to 1.3 degrees  in the period between 3 months and final follow-up. This was
      statistically significant (p = 0.002), indicating that most of the fall in neck
      shaft angle occurs in the first three months after surgery. Relationship between
      neck shaft angle change and age (p = 0.29), fracture pattern (p = 0.41), cortical
      thickness (p = 0.21), medial support (p = 0.63) and initial reduction accuracy (p
      = 0.65) are not statistically significant. CONCLUSIONS: The proximal humerus
      locking plate maintains reliable radiographic results even in the elderly
      population with proximal humerus fracture.

PMID- 22949953
TI  - Positive or negative ulnar variance after ulnar shortening for ulnar impaction
      syndrome: a retrospective study.
AB  - BACKGROUND: The goal of this study was to compare simple radiographic findings
      and clinical results according to residual ulnar variance following ulnar
      shortening for ulnar impaction syndrome. METHODS: Forty-five cases of ulnar
      impaction syndrome, which were treated with ulnar shortening from 2005 to 2008,
      were studied retrospectively. Group I included 13 cases with positive residual
      variance after ulnar shortening and group II included 32 cases with negative
      variance after shortening. The presence of a lunate cystic lesion both
      preoperatively and at final follow-up and assessments of wrist function based on
      the modified Mayo wrist score, the disabilities of the arm, shoulder, and hand
      (DASH) score, as well as the Chun and Palmer score were evaluated. RESULTS: A
      cystic lesion of the lunate was present in 4 cases preoperatively and the size
      decreased in 2 cases at final follow-up in group I, and in 10 and 5 cases,
      respectively, in group II. No statistical difference was observed between the
      groups. The modified Mayo wrist score, DASH score, as well as the Chun and Palmer
      score improved significantly in both groups. No significant differences were
      observed between the two groups in terms of the proportion of positive cystic
      lesions at final follow-up or the functional scores. CONCLUSIONS: After ulnar
      shortening, the degree of radiological change in the cystic lunate lesions and
      clinical improvement did not differ significantly between the groups with
      unintended residual positive and negative variance after shortening.

PMID- 22949954
TI  - Revisit of Broden's view for intraarticular calcaneal fracture.
AB  - BACKGROUND: This study was performed to investigate the relationship between
      coronal computed tomography (CT) and Broden's view in terms of location of the
      fracture line and fracture pattern. METHODS: Forty-five feet of 45 patients with
      intraarticular calcaneal fractures were evaluated. The mean age of the patients
      was 46.3 years (standard deviation, 18.1; range, 15 to 80 years), and there were
      34 men and 11 women. The Broden's views were acquired using the ray sum
      projection, reviewed, and correlated with the coronal CT image to determine the
      location of the fracture on the posterior facet and fracture pattern described by
      the Sanders classification. The quantified location of the fracture line was
      defined as the distance between the medial margin of posterior facet and the
      fracture line divided by the whole length of the posterior facet, which was
      expressed as a percentage. RESULTS: The fracture line on the Broden's view was
      positioned at 22.3% (standard deviation, 29.6) laterally compared to that on
      coronal CT (p < 0.01). Although all cases showed posterior facet involvement on
      the CT scan, the fracture line was positioned lateral to the posterior facet in 6
      cases (13.3%) in the Broden's view. The coronal CT and Broden's view showed a low
      level of agreement in the fracture pattern according to the Sanders
      classification, with kappa values of 0.23. CONCLUSIONS: Surgeons should consider
      that the fracture line on the Broden's view shows positioning laterally compared
      to coronal CT and they should consider that the fracture line at the lateral to
      posterior facet on the Broden's view might be an intraarticular fracture line.
      There are some limitations when applying the Sanders classification with the
      Broden's view.

PMID- 22949955
TI  - Clinical analysis of femur shaft insufficiency fractures.
AB  - BACKGROUND: To characterize the recently issued femur shaft insufficiency
      fracture in terms of a patient's own epidemiological status. METHODS: Fourteen
      patients were treated for insufficiency fracture from July 2002 to June 2008,
      excluding cases including the risk factors of insufficiency fracture. All
      patients were female, and their mean age was 75.6 years (range, 65 to 89 years).
      The mean follow-up period was 50.6 months (range, 14 to 86 months). RESULTS: The
      mean body weight of the Koreans in the same age group was 58.1 +/- 9.7 kg, and
      the mean height was 155.5 +/- 8.8 cm. The mean body weight of our insufficiency
      fracture patients was 45.7 kg and it was statistically significantly lower than
      that of the Koreans in the same age group (p < 0.001). The mean height was 147.3
      cm and it was significantly shorter than the mean height of the Koreans in the
      same age group (p = 0.002). In regard to menopausal time, the mean menopausal
      time of the Koreans was 48.0 +/- 4.2 years, it was 44 years in our study, as
      menopause occurred statistically significantly earlier (p = 0.017). The patients
      with insufficiency fracture showed statistically lower weight, shorter stature
      and an earlier menopausal period than that of the general population.
      CONCLUSIONS: In early menopausal, underweight, and short patients prescribed
      osteoporosis medication for an extended period of time, if predromal symptom is
      present, it is necessary to suspect insufficiency fracture of the femur.

PMID- 22949957
TI  - Modified Mason-Allen suture bridge technique: a new suture bridge technique with
      improved tissue holding by the modified Mason-Allen stitch.
AB  - We present a new method of suture bridge technique for medial row fixation using
      a modified Mason-Allen stitch instead of a horizontal mattress. Medial row
      configuration of the technique is composed of the simple stitch limb and the
      modified Mason-Allen stitch limb. The limbs are passed through the tendon by a
      shuttle relay. The simple stitch limb passes the cuff once and the modified Mason
      Allen stitch limb passes three times which creates a rip stop that prevents
      tendon pull-out. In addition, the Mason-Allen suture bridge configuration is
      basically a knotless technique which has an advantage of reducing a possibility
      of strangulation of the rotator cuff tendon, impingement or irritation that may
      be caused by knot.

PMID- 22949956
TI  - Effect of combined sex hormone replacement on bone/cartilage turnover in a murine
      model of osteoarthritis.
AB  - BACKGROUND: Estrogens act on estrogen receptors distributed in articular
      cartilages, synovial membrane, and ligaments, which are thought to be related
      with degenerative changes. Meanwhile, progesterone is known to have a weak
      anabolic action on bone formation This study evaluates the effects of estrogen
      and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats.
      METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided
      into 5 groups and then ovariectomized bilaterally except the sham control group.
      The first and the second group acting as controls did not receive hormonal
      therapy, the third group received estrogen, the fourth group received
      progesterone, and the fifth group received combination of both hormones 10 weeks
      after surgery. Evaluations were done using the serum levels of cartilage
      oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C
      telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks
      after OVX and histology using the Osteoarthritis Research Society International
      (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS:
      Significantly less cartilage degradation (decreased levels of COMP) was found in
      the combined hormone treated group in comparison with OVX group. Similarly, both
      hormonal treatment resulted in increased bone formation and decreased bone
      resorption i.e., a low overall bone turnover status (decrease in the serum OC and
      CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found
      to be convincing in terms of reducing the severity of OA in this experimental
      model.

PMID- 22949958
TI  - Bilateral carpometacarpal joint dislocations of the thumb.
AB  - A traumatic carpometacarpal joint dislocation of the thumb accounts for less than
      1% of all hand injuries. Optimal treatment strategies for this injury are still a
      subject of debate. In this article, we report a case of bilateral thumb
      carpometacarpal joint dislocations: a unique combination of injuries. We believe
      our case is the second report of bilateral carpometacarpal joint dislocation
      regarding the thumb in English literature. It was successfully treated with
      closed reduction and percutaneous K-wires fixation on one side, and an open
      reduction and reconstruction of the ligament on the other side.

PMID- 22949959
TI  - The Change of Bone Metabolism in Ovariectomized Rats : Analyses of MicroCT Scan
      and Biochemical Markers of Bone Turnover.
AB  - OBJECTIVE: The purpose of this study was to verify the appropriateness of
      ovariectomized rats as the osteoporosis animal model. METHODS: Twelve female
      Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral
      ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum
      biochemical markers of bone turnover were analyzed; osteocalcin and alkaline
      phosphatase, which are sensitive biochemical markers of bone formation, and C
      terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a
      sensitive biochemical marker of bone resorption. Bone histomorphometric
      parameters and microarchitectural properties of 4th lumbar vertebrae were
      determined by micro-computed tomographic (CT) scan. RESULTS: The OVX group showed
      on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham
      group, indicating increased bone turnover. Micro-CT analysis showed significantly
      lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX
      group. Furthermore, the OVX group was found to have a significantly lower
      trabecular bone volume fraction (p=0.002). CONCLUSION: Our results showed that
      bone turnover was significantly increased and bone mass was significantly
      decreased 8 weeks after ovariectomy in rats. Thus, we propose that the
      ovariectomized rat model be considered a reproducible and reliable model of
      osteoporosis.

PMID- 22949960
TI  - Increased Vascular Endothelial Growth Factor in the Ventricular Cerebrospinal
      Fluid as a Predictive Marker for Subsequent Ventriculoperitoneal Shunt Infection
      : A Comparison Study among Hydrocephalic Patients.
AB  - OBJECTIVE: The aim of this study is to determine the association between the
      cerebrospinal fluid (CSF) biomarkers and inflammation, and the predictive value
      of these CSF biomarkers for subsequent shunt associated infection. METHODS: We
      obtained CSF samples from the patients with hydrocephalus during
      ventriculoperitoneal (VP) shunt operations. Twenty-two patients were enrolled for
      this study and divided into 3 groups: subarachnoid hemorrhage (SAH)-induced
      hydrocephalus, idiopathic normal pressure hydrocephalus (INPH) and hydrocephalus
      with a subsequent shunt infection. We analyzed the transforming growth factor
      beta1, tumor necrosis factor-alpha, vascular endothelial growth factor (VEGF) and
      total tau in the CSF by performing enzyme-linked immunosorbent assay. The
      subsequent development of shunt infection was confirmed by the clinical
      presentations, the CSF parameters and CSF culture from the shunt devices.
      RESULTS: The mean VEGF concentration (+/-standard deviation) in the CSF of the
      SAH-induced hydrocephalus, INPH and shunt infection groups was 236+/-138, 237+/
      80 and 627+/-391 pg/mL, respectively. There was a significant difference among
      the three groups (p=0.01). Between the SAH-induced hydrocephalus and infection
      groups and between the INPH and infection groups, there was a significant
      difference of the VEGF levels (p<0.01). However, the other marker levels did not
      differ among them. CONCLUSION: The present study showed that only the CSF VEGF
      levels are associated with the subsequent development of shunt infection. Our
      results suggest that increased CSF VEGF could provide a good condition for
      bacteria that are introduced at the time of surgery to grow in the brain, rather
      than reflecting a sequel of bacterial infection before VP shunt.

PMID- 22949961
TI  - Comparison between Lateral Supraorbital Approach and Pterional Approach in the
      Surgical Treatment of Unruptured Intracranial Aneurysms.
AB  - OBJECTIVE: The lateral supraorbital (LSO) approach is a modified method of the
      classic pterional approach and it has advantages of short skin incision and small
      craniotomy compared with the pterional approach. This study was designed to
      compare the two approaches in the surgical treatment of unruptured intracranial
      aneurysms. METHODS: We retrospectively reviewed 122 patients with 137 unruptured
      intracranial aneurysms treated by clipping, from July 2009 to April 2011. Between
      August 2010 and April 2011, 61 patients were treated by clipping via the lateral
      supraorbital approach and the same number of patients treated by clipping via the
      pterional approach were retrospectively enrolled. We analyzed the two groups and
      compared demographic, radiologic and clinical variables. RESULTS: The mean age of
      patients in the two groups was 54.6 years (LSO group) and 55.7 years (Pterion
      group). The mean duration of hospitalization was shorter in the LSO group than in
      the Pterion group (7.9 days vs. 9.0 days, p=0.125) and the mean operation time
      was also significantly shorter in the LSO group (117.1 minutes vs. 164.3 minutes,
      p<0.001). Furthermore, the mean craniotomy area was much smaller in the LSO group
      (1275.4 mm(2) vs. 2858.9 mm(2), p<0.001). The two groups showed similar
      distributions of aneurysm location and postoperative complications. CONCLUSION:
      The lateral supraorbital approach for the clipping of unruptured intracranial
      aneurysm could be a good alternative to the classic pterional approach.

PMID- 22949962
TI  - Implementation and outcomes of a critical pathway for lumbar laminectomy or
      microdiscectomy.
AB  - OBJECTIVE: The aim of this study is to implement a critical pathway (CP) for
      patients undergoing lumbar laminectomy or microdiscectomy and describe the
      results before and after the CP in terms of length of hospital stay and cost.
      METHODS: From March 2008 to February 2009, 61 patients underwent lumbar
      laminectomy or microdiscectomy due to stenosis or one- or two-level disc
      herniation in our department and were included in the prepathway group. After
      development and implementation of the CP in March 2009, 58 patients were
      applicable for the CP, and these were classified as the postpathway group.
      RESULTS: The CP, which established a 6-day hospital stay (5 bed-days), was
      fulfilled by 42 patients (72.4%) in the postpathway group. The mean length of
      stay was 5.4 days in the postpathway group compared to 6.9 days in the prepathway
      group, demonstrating a 20% reduction, which was a statistically significant
      difference (p<=0.000). There was a statistically significant reduction in charges
      for bed and nursing care (p=0.002). CONCLUSION: Implementation of a CP for lumbar
      laminectomy or microdiscectomy produced significant decreases in length of
      hospitalization and charges for bed and nursing care. We believe that this CP
      reduces the unnecessary use of hospital resources without increasing risk of
      adverse events.

PMID- 22949963
TI  - NFlex Dynamic Stabilization System : Two-Year Clinical Outcomes of Multi-Center
      Study.
AB  - OBJECTIVE: Pedicle-based dynamic stabilization systems, in which semi-rigid rods
      or cords are used to restrict or control spinal segmental motion, aim to reduce
      or eliminate the drawbacks associated with rigid fusion. In this study, we
      analyzed the two-year clinical outcomes of patients treated with the NFlex
      (Synthes Spine, Inc.), a pedicle-based dynamic stabilization system. METHODS:
      Five sites participated in a retrospective study of 72 consecutive patients who
      underwent NFlex stabilization. Of these 72 patients, 65 were available for 2-year
      follow-up. Patients were included based on the presence of degenerative disc
      disease (29 patients), degenerative spondylolisthesis (16 patients), lumbar
      stenosis (9 patients), adjacent segment degeneration (6 patients), and
      degenerative lumbar scoliosis (5 patients). The clinical outcome measures at each
      assessment were Visual Analogue Scale (VAS) to measure back pain, and Oswestry
      Disability Index (ODI) to measure functional status. Radiographic assessments
      included evidence of instrumentation failure or screw loosening. RESULTS: Sixty
      five patients (26 men and 39 women) with a mean age of 54.5 years were included.
      Mean follow-up was 25.6 months. The mean VAS score improved from 8.1
      preoperatively to 3.8 postoperatively, representing a 53% improvement, and the
      ODI score from 44.5 to 21.8, representing a 51% improvement. Improvements in pain
      and disability scores were statistically significant. Three implant-related
      complications were observed. CONCLUSION: Posterior pedicle-based dynamic
      stabilization using the NFlex system seems effective in improving pain and
      functional scores, with sustained clinical improvement after two years. With
      appropriate patient selection, it may be considered an effective alternative to
      rigid fusion.

PMID- 22949964
TI  - Perioperative risk factors related to lumbar spine fusion surgery in korean
      geriatric patients.
AB  - OBJECTIVE: Life expectancy for humans has increased dramatically and with this
      there has been a considerable increase in the number of patients suffering from
      lumbar spine disease. Symptomatic lumbar spinal disease should be treated, even
      in the elderly, and surgical procedures such as fusion surgery are needed for
      moderate to severe lumbar spinal disease. However, various perioperative
      complications are associated with fusion surgery. The aim of this study was to
      examine perioperative complications and assess risk factors associated with
      lumbar spinal fusion, focusing on geriatric patients at least 70 years of age in
      the Republic of Korea. METHODS: We retrospectively investigated 489 patients with
      various lumbar spinal diseases who underwent lumbar spinal fusion surgery between
      2003 and 2007 at our institution. Three fusion procedures and the number of fused
      segments were analyzed in this study. Chronic diseases were also evaluated. Risk
      factors for complications and their association with age were analyzed. RESULTS:
      In this study, 74 patients experienced complications (15%). The rate of
      perioperative complications was significantly higher in patients 70 years of age
      or older than in other age groups (univariate analysis, p=0.001; multivariate
      analysis, p=0.004). However, perioperative complications were not significantly
      associated with the other factors tested (sex, comorbidities, operation
      procedures, fusion segments involved). CONCLUSION: Increasing age was an
      important risk factor for perioperative complications in patients undergoing
      lumbar spinal fusion surgery whereas other factors were not significant. We
      recommend good clinical judgment and careful selection of geriatric patients
      undergoing lumbar spinal fusion surgery.

PMID- 22949965
TI  - The effect of surgery time on prognosis in newborns with meningomyelocele.
AB  - OBJECTIVE: To investigate the effect of surgery time on prognosis of newborns
      with meningomyelocele. METHODS: The records of neonates with meningomyelocele
      were retrospectively analyzed. Demographic and clinical characteristics as well
      as information, timing of surgery, and durations of hospital stay and antibiotic
      therapy were recorded. RESULTS: The records of 30 babies were included in the
      final analysis. Overall, the mean gestational age was 37.7+/-2.7 weeks, with a
      mean birth weight of 2967+/-755 g and head circumference of 35.8+/-3.8 cm. In
      terms of localization, 46.6% of the meningomyeloceles were lumbosacral, 40% were
      lumbar, 10% were thoracolumbar and 3.3% were thoracal. The mean size of the
      meningomyelocele sacs was 4.33+/-1.2 cm. Newborns underwent surgery on average of
      8.2+/-5.9 days after birth, with an overall mean duration of hospital stay of
      30+/-25.1 days. Patients were divided into two groups based on timing of surgery
      (group 1, <=5 days; group 2, >5 days), and comparisons between groups revealed
      that earlier surgery was associated with significantly shorter durations of
      hospital stay (p<0.001) and antibiotic therapy (p<0.05). CONCLUSION: Early
      surgical intervention (<=5 days) was associated with a shorter duration of
      hospital stay and antibiotic therapy as well as a lower complication rate. We
      recommend that corrective surgery be undertaken as soon as reasonably possible.

PMID- 22949966
TI  - Neurolysis for meralgia paresthetica.
AB  - OBJECTIVE: Meralgia paresthetica (MP) is a syndrome of pain and/or dysesthesia in
      the anterolateral thigh that is caused by an entrapment of the lateral femoral
      cutaneous nerve (LFCN) at its pelvic exit. Despite early accounts of MP, there is
      still no consensus concerning the effectiveness of neurolysis or transaction
      treatments in the long-term relief for medically refractory patients with MP. We
      retrospectively analyzed available long-term results of LFCN neurolysis for
      medically refractory MP in an effort to clarify this issue. METHODS: During the
      last 7 years, 11 patients who had neurolysis for MP were enrolled in this study.
      Nerve entrapment was confirmed preoperatively by electrophysiological studies or
      a positive response to local anesthetic injection. Decompression of the LFCN was
      performed at the level of the iliac fascia, inguinal ligament, and fascia of the
      thigh distally. The outcome of surgery was assessed 8 weeks after the procedure
      followed at regular intervals if symptoms persisted. RESULTS: Twelve
      decompression procedures were performed in 11 patients over a 7-year period. The
      average duration of symptoms was 8.5 months (range, 4-15 months). The average
      follow-up period was 33 months (range, 12-60 months). Complete and partial
      symptom improvement were noted in nine (81.8%) and two (18.2%) cases,
      respectively. No recurrence was reported. CONCLUSION: Neurolysis of the LFCN can
      provide adequate pain relief with minimal complications for medically refractory
      MP. To achieve a good outcome in neurolysis for MP, an accurate diagnosis with
      careful examination and repeated blocks of the LFCN, along with electrodiagnosis
      seems to be essential. Possible variation in the course of the LFCN and thorough
      decompression along the course of the LFCN should be kept in mind in planning
      decompression surgery for MP.

PMID- 22949967
TI  - Terson syndrome caused by intraventricular hemorrhage associated with moyamoya
      disease.
AB  - Terson syndrome was originally used to describe a vitreous hemorrhage arising
      from aneurysmal subrarachnoid hemorrhage. Terson syndrome can be caused by
      intracranial hemorrhage, subdural or epidural hematoma and severe brain injury
      but is extremely rare in intraventricular hemorrhage associated with moyamoya
      disease. A 41-year-old man presented with left visual disturbance. He had a
      history of intraventicular hemorrhage associated with moyamoya disease three
      months prior to admission. At that time he was in comatose mentality.
      Ophthalmologic examination at our hospital detected a vitreous hemorrhage in his
      left eye, with right eye remaining normal. Vitrectomy with epiretinal membrane
      removal was performed. After operation his left visual acuity was recovered.
      Careful ophthalmologic examination is mandatory in patients with hemorrhagic
      moyamoya disease.

PMID- 22949968
TI  - In-stent stenosis of stent-assisted coil embolization of the supraclinoid
      internal carotid artery aneurysm.
AB  - The intracranial stent functions primarily to prevent protrusion of coils into
      the parent vessel during the embolization of wide-necked cerebral aneurysms and
      might also reduce aneurysm recanalization rate. In spite of these advantages,
      little is known about the long-term interaction of the stent with the parent
      vessel wall. We present a rare case of severe in-stent stenosis occurring as a
      delayed complication of Neuroform stent-assisted coil embolization of an
      unruptured intracranial aneurysm.

PMID- 22949969
TI  - Retained microcatheter after onyx embolization of intracranial arteriovenous
      malformation.
AB  - Endovascular embolization is being increasingly used to treat intracranial
      arteriovenous malformations (AVMs). However, we experienced two patients with
      retained microcatheters after AVM embolization using Onyx.

PMID- 22949970
TI  - Gastric mucosa-associated lymphoid tissue lymphoma followed by primary central
      nervous system lymphoma.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is one of the most common
      lymphomas and accounts for about 7% of all newly diagnosed non-Hodgkin's lymphoma
      (NHL). The clinical course of MALT lymphoma is relatively indolent and, in the
      majority of cases (50%), the lymphoma arises within the stomach. Primary central
      nervous system lymphoma (PCNSL), an uncommon variant of extranodal NHL, can
      affect any part of the neuraxis, including the eyes, brain, leptomeninges, or
      spinal cord. Herein, we present a rare case of PCNSL, which occurred one year
      after radiochemotherapy of gastric MALT lymphoma. A 62-year-old man presented
      with a 3-day history of left facial palsy. One year ago, he underwent antibiotic
      eradication therapy of Helicobacter pylori, local stomach fractional
      radiotherapy, and chemotherapy for gastric MALT lymphoma. Magnetic resonance
      imaging revealed a strong enhancing solid mass in the right frontal lobe. The
      tumor was completely removed, and the histological diagnosis of PCNSL developing
      from diffuse large B-cell lymphoma was made. Although elucidating the correlation
      between the first gastric MALT lymphoma and the second PCNSL seemed difficult, we
      have postulated and discussed some possible pathogeneses, together with a review
      of literature.

PMID- 22949971
TI  - Recurrent bacterial meningitis accompanied by a spinal intramedullary abscess.
AB  - Bacterial meningitis is rarely complicated by an intradural spinal abscess, and
      recurrent meningitis is an uncommon presentation of a spinal intramedullary
      abscess. Here, we report a 63-year-old patient with recurrent meningitis as the
      first manifestation of an underlying spinal intramedullary abscess. To the best
      of our knowledge, no previous report has been issued on recurrent meningitis
      accompanied by a spinal intramedullary abscess in an adult. In this article, the
      pathophysiological mechanism of this uncommon entity is discussed and the
      relevant literature reviewed.

PMID- 22949972
TI  - Surgical management of cervical spinal epidural abscess caused by Brucella
      melitensis : report of two cases and review of the literature.
AB  - Spinal epidural abscess, if especially caused by Brucellosis is a very rare
      disease which is usually a consequence of spondylodiscitis. The spinal column can
      be affected at any joint; however, the lumbar spine is the most common region,
      especially at the level of the L4-5 and L5-S1. The frequency of spinal
      involvement usually seen at the lumbar, thoracic and cervical spine respectively.
      As an occupational disease in farmers, veterinaries, butchers, laboratory staff
      and shepherds, brucellosis can also occur by direct contact to animals and
      infected materials or ingestion of raw cheese, milk or unpasteurized milk
      products. In this study, we presented two cases with cervical spinal epidural
      abscess caused by brucella melitensis, which was successfully treated by surgical
      approach. Initial treatment was combined with antibiotic therapy after the
      surgery for 3 months.

PMID- 22949973
TI  - Spondylolisthesis accompanying bilateral pedicle stress fracture at two
      vertebrae.
AB  - There has been no report of bilateral pedicle stress fractures involving two
      vertebrae. The authors describe a unique case of spondylolisthesis accompanying a
      bilateral pedicle stress fracture involving two vertebrae. De novo development of
      spondylolisthesis at the L5-S1 vertebrae accompanying a bilateral pedicle stress
      fracture at L4 and L5 was observed in a 70-year-old woman. The patient's medical
      history was unremarkable and she did not have any predisposing factors except
      severe osteoporosis. Interbody fusion with bone cement augmented screw fixation
      was performed. Surgical treatment resulted in good pain management and improved
      functional recovery.

PMID- 22949974
TI  - Seeing is believing: ultrasound guidance for central venous access in clinical
      anesthesia.

PMID- 22949975
TI  - Remifentanil used as adjuvant in general anesthesia for spinal fusion does not
      exhibit acute opioid tolerance.
AB  - BACKGROUND: Although acute tolerance to opioids, especially to remifentanil, has
      been demonstrated consistently in animal studies, the results of clinical trials
      in humans are controversial. The aim of this study was to determine whether
      intraoperative infusions of remifentanil used as an adjuvant in general
      anesthesia result in acute tolerance, an event manifested by increased
      postoperative pain and a higher opioid requirement than usual. METHODS: Sixty
      patients who underwent surgery under general anesthesia for spinal fusion were
      randomly assigned to receive sevoflurane-nitrous oxide-oxygen (group SO, n = 20),
      sevoflurane-remifentanil-nitrous oxide-oxygen (group SR, n = 20), or propofol
      remifentanil-oxygen (group PR, n = 20) in a double-blinded manner. All patients
      within 1 hour after induction received PCA (fentanyl 0.4 ug/kg/ml and ondansetron
      16 mg) administered intravenously at a basal infusion rate of 1 ml/h, after being
      intravenously injected with a loading dose of fentanyl (1 ug/kg). Data for
      fentanyl requirement, verbal Numerical Rating Scale (NRS) pain score at rest, and
      presence of nausea or vomiting were collected at 1, 24, and 48 hours after
      surgery. RESULTS: We did not find any significant difference in postoperative PCA
      fentanyl requirements, NRS or side effects among the groups. CONCLUSIONS:
      Remifentanil as an adjuvant to sevoflurane or propofol in general anesthesia for
      adults having surgery for spinal fusion does not appear to cause acute opioid
      tolerance or hyperalgesia in patients. However, further studies are needed to
      elucidate whether sevoflurane and propofol exert a clinically significant effect
      on opioid-induced tolerance or hyperalgesia and whether this effect is related to
      the age of the patient, the dose and duration of remifentanil given and the
      intensity of pain experienced postoperatively.

PMID- 22949976
TI  - The optimal effect-site concentration of remifentanil to attenuate the pain
      caused by propofol.
AB  - BACKGROUND: The injection pain of propofol is a frequent and well-known adverse
      effect. This study was designed to determine the optimal effect-site
      concentration of remifentanil for minimizing injection pain during induction with
      propofol. METHODS: A total intravenous anesthetic technique was used for patients
      undergoing general anesthesia and remifentanil was pretreated to reach a certain
      target concentration before propofol injection. Using Dixon's up-and-down method,
      the degree of pain described by the patient was used to adjust the target
      concentration of remifentanil for the next patient. Ten success-failure curves
      (crossovers) were sought to find the effect-site concentration (EC) of
      remifentanil for minimizing injection pain of propofol. RESULTS: The EC of
      remifentanil in 50% and 95% of adult female population (EC(50) and EC(95)) for
      minimizing injection pain of propofol were 3.09 ng/ml (95% confidence limits [CI]
      2.92-3.30 ng/ml) and 3.78 ng/ml (95% CI 3.45-3.95 ng/ml), respectively.
      Clinically significant hemodynamic compromise or respiratory complications were
      not found during remifentanil infusion. CONCLUSIONS: Maintaining 3.78 ng/ml EC of
      remifentanil during induction with propofol attenuate propofol injection pain
      without serious adverse events in female patients undergoing general anesthesia
      and this method may provide the patient's comfort without preparing other drugs
      for pain relief.

PMID- 22949977
TI  - Perioperative effects of various anesthetic adjuvants with TIVA guided by
      bispectral index.
AB  - BACKGROUND: This prospective, randomized, double blinded, controlled study was
      designed to compare effects of intravenous co-administration of clonidine,
      magnesium, or ketamine on anesthetic consumption, intraoperative hemodynamics,
      postoperative analgesia and recovery indices during Bispectral Index (BIS) guided
      total intravenous anesthesia (TIVA). METHODS: After ethical committee approval
      and written informed consent, 120 adult patients ASA I and II scheduled for open
      cholecystectomy were randomly assigned to one of 4 equal groups. Group CL
      received clonidine 3 ug/kg and maintained by 2 ug/kg/h. Group MG received
      magnesium sulphate 50 mg/kg and maintained by 8 mg/kg/h. Group KET received
      racemic ketamine 0.4 mg/kg and maintained by 0.2 mg/kg/h. Control group (CT)
      received the same volume of isotonic saline. Anesthesia was induced and
      maintained by fentanyl, propofol and rocuronium. Propofol infusion was adjusted
      to keep the BIS value between 45-55. Intraoperative hemodynamics, induction time,
      anesthetic consumption, recovery indices, and PACU discharge were recorded.
      RESULTS: Induction time, propofol requirements for induction and maintenance of
      anesthesia, intraoperative fentanyl and hemodynamic values were significantly
      lower with Groups CL and MG compared to Groups KET and CT (P < 0.05). Patients in
      Group MG showed significantly lower muscle relaxant consumption, delayed recovery
      and PACU discharge than other groups (P < 0.05). First, analgesic requirement was
      significantly longer and total postoperative analgesic consumption was
      significantly lower in the adjuvant groups versus Group CT (P < 0.05).
      CONCLUSIONS: Clonidine, magnesium, and ketamine can be useful adjuvant agents to
      BIS-guided TIVA. Pharmacokinetic studies of such drug combinations were
      recommended to investigate their interaction.

PMID- 22949978
TI  - Urinary trypsin inhibitor attenuates liver enzyme elevation after liver
      resection.
AB  - BACKGROUND: Urinary trypsin inhibitors (UTI) have been widely used for the
      treatment of diseases including disseminated intravascular coagulation, shock,
      and pancreatitis. Since UTI synthesis is likely to be reduced in patients who
      have undergone liver resection, the incidence of inflammatory reactions may be
      increasing accordingly. For such patients, the liver enzyme increases after the
      operation can reflect liver damage. The purpose of this study was to examine if
      ulinastatin can inhibit liver enzyme increases after liver resection. METHODS:
      After receiving Institutional Review Board approval, a retrospective chart review
      was performed on 201 patients who underwent hepatic resection from 2006 to 2010.
      We divided the records into the control (n = 69) and ulinastatin (n = 132) groups
      according to the use of intraoperative ulinastatin and compared the preoperative
      and postoperative laboratory test results. The number of patients who had > 400
      U/L elevation of aspartate transaminase (AST) level after surgery was compared
      between the 2 groups. RESULTS: The mean AST, alanine transaminase (ALT), and
      total bilirubin levels after liver resection were significantly lower in the
      ulinastatin group than in the control group. The number of patients who showed an
      AST > 400 U/L after liver resection was significantly higher in the control group
      (odds ratio = 3.02). CONCLUSIONS: Ulinastatin attenuates the elevation of hepatic
      enzymes and bilirubin after liver resection.

PMID- 22949979
TI  - Comparison of dexmedetomidine and remifentanil for attenuation of hemodynamic
      responses to laryngoscopy and tracheal intubation.
AB  - BACKGROUND: This study was designed to compare the effect of dexmedetomidine and
      remifentanil used in anesthetic induction on hemodynamic change after direct
      laryngoscopy and tracheal intubation. METHODS: A total of 90 ASA class 1 or 2
      patients were randomly assigned to one of 3 groups to receive one of the
      following treatments in a double-blind manner: normal saline (Group C, n = 30),
      dexmedetomidine 1 ug/kg (Group D, n = 30), remifentanil 1 ug/kg (Group R, n= 30).
      Anesthesia was induced with propofol 2 mg/kg and rocuronium 0.6 mg/kg and
      maintained with 2 vol% sevoflurane and 50% nitrous oxide in oxygen. In group D,
      dexmedetomidine 1 ug/kg was infused for 10 min before tracheal intubation.
      Patients in group R was received 1 ug/kg of remifentanil 1 minute before tracheal
      intubation. The systolic blood pressure, diastolic blood pressure and heart rate
      were recorded from entrance to operation room to 5 min after tracheal intubation.
      RESULTS: The percent increase in systolic and diastolic blood pressure due to
      tracheal intubation in group D and R were significantly lower than that of group
      C (P < 0.05). The heart rate 1 min after tracheal intubation was lower in groups
      R and D than in the group C (P < 0.05). CONCLUSIONS: In healthy normotensive
      patients, the use of dexmedetomidine during anesthetic induction suppressed a
      decrease in blood pressure due to anesthetic induction and blunted the
      hemodynamic responses to endotracheal intubation.

PMID- 22949980
TI  - A comparison of hemodynamic changes after endotracheal intubation by the
      OptiscopeTM and the conventional laryngoscope.
AB  - BACKGROUND: OptiscopeTM is a newly developed video stylet device. This study
      evaluated and compared the hemodynamic changes observed after endotracheal
      intubation with video stylet and after conventional laryngoscopic endotracheal
      intubation. METHODS: Fifty-eight adult patients with American Society of
      Anesthesiologists (ASA) physical status class 1 or 2, undergoing general
      anesthesia, were randomized into two groups: one group of patients were intubated
      using video stylet (n = 29) and the other group were intubated using direct
      laryngoscope (n = 29). Systolic blood pressure (SBP), mean arterial pressure
      (MAP), diastolic blood pressure (DBP), heart rate (HR), POGO (percentage of
      glottic opening) score, time for intubation and degree of sore throat were
      recorded. RESULTS: There were no significant differences in the SBP, MAP, DBP,
      HR, and the sore throat incidence between the two groups. OptiscopeTM produced
      better POGO scores, but time for intubation was longer than with conventional
      laryngoscope. CONCLUSIONS: OptiscopeTM, when compared with conventional
      laryngoscope for intubation, does not modify the hemodynamic response, but it
      provides a better view of the vocal cords.

PMID- 22949981
TI  - Comparison of the clinical effectiveness between the streamlined liner of
      pharyngeal airway (SLIPA) and the laryngeal mask airway by novice personnel.
AB  - BACKGROUND: The aim of this study was to compare the streamlined liner of the
      pharynx airway (SLIPA) with the classic laryngeal mask airway when used by novice
      personnel. METHODS: There were 114 patients enrolled into this study who
      underwent general anesthesia were randomly allocated into one of 2 groups; LMA
      group (n = 57) or SLIPA group (n = 57). After insertion, insertion success rate,
      insertion time, and hemodynamic responses to insertion were accessed. After
      surgery, postoperative airway morbidity (sore throat, dysphonia, dysphagia) were
      evaluated. RESULTS: The SLIPA was successfully inserted in 96% of patients
      (55/57) and the LMA in 93% (53/57) (P = 0.408). First attempt success rates were
      88% (44/57) and 77% (50/57) in the SLIPA and the LMA (P = 0.142). The successful
      insertion time in SLIPA group (33.4 +/- 11.0 sec) was significantly shorter than
      that of LMA group (38.8 +/- 16.6 sec) (P = 0.048) and the insertion time at the
      first attempt was also shorter in SLIPA group (31.0 +/- 6.3 sec) than LMA group
      (34.7 +/- 8.6 sec) (P = 0.013). There was no statistically significant difference
      between the two groups in hemodynamic responses and postoperative airway
      morbidity. CONCLUSIONS: The SLIPA was similar to the LMA in insertion success
      rate, hemodynamic response, and postoperative airway morbidity by novice
      personnel. The insertion time at the first attempt and successful insertion time
      of the SLIPA were significantly shorter than those of the LMA. Therefore, the
      SLIPA could be a useful alternative to the LMA as primary SGA for novice
      personnel.

PMID- 22949982
TI  - Effect of a single bolus of methylene blue prophylaxis on vasopressor and
      transfusion requirement in infective endocarditis patients undergoing cardiac
      surgery.
AB  - BACKGROUND: The accentuated nitric oxide (NO) release that is induced by the
      systemic inflammatory response associated with infective endocarditis (IE) and
      cardiopulmonary bypass (CPB) may result in catecholamine refractory hypotension
      (vasoplegia) and increased transfusion requirement due to platelet inhibition.
      Methylene blue (MB) is an inhibitory drug of inducible NO. We aimed to evaluate
      the effect of prophylactic MB administration before CPB on vasopressor and
      transfusion requirements in patients with IE undergoing valvular heart surgery
      (VHS). METHODS: Forty-two adult patients were randomly assigned to receive 2
      mg/kg of MB (MB group, n = 21) or saline (control group, n = 21) for 20 min
      before the initiation of CPB. The primary end points were comparisons of
      vasopressor requirements serially assessed after weaning from CPB and hemodynamic
      parameters serially recorded before and after CPB. The secondary endpoint was the
      comparison of transfusion requirements. RESULTS: Two patients in the control
      group received MB after weaning from CPB due to norepinephrine and vasopressin
      refractory vasoplegia and were thus excluded. There were no significant
      differences in vasopressor requirements and hemodynamic parameters between the
      two groups. The mean number of units of packed erythrocytes transfused per
      transfused patient was significantly less in the MB group. The numbers of
      patients transfused with fresh frozen plasma and platelet concentrates were less
      in the MB group. CONCLUSIONS: In IE patients undergoing VHS, prophylactic MB
      administration before CPB did not confer significant benefits in terms of
      vasopressor requirements and hemodynamic parameters, but it was associated with a
      significant reduction in transfusion requirement.

PMID- 22949983
TI  - Effect of superoxide on the development and maintenance of mechanical allodynia
      in a rat model of chronic post-ischemia pain.
AB  - BACKGROUND: Reactive oxygen species and inflammatory responses contribute to the
      development of neuropathic pain. Superoxide serves to mediate cell signaling
      processes and tissue injury during inflammation. We examined the effects of
      superoxide on the development and maintenance of mechanical allodynia, as well as
      its contribution to central sensitization in a superoxide-rich animal model of
      neuropathic pain. METHODS: Chronic post-ischemia pain (CPIP) was induced via the
      left hindpaw ischemia for 3 h, followed by reperfusion. Superoxide dismutase
      (4,000 U/kg, i.p.) was administered either 5 min before ischemia (BI), 5 min
      before reperfusion (BR), or 3 days after reperfusion (3AR). Withdrawal thresholds
      of the four paws were measured to assess the mechanical allodynia and the effects
      of circulating xanthine oxidase (XO)-mediated superoxide production. In addition,
      we measured the levels of N-methyl D-aspartate receptor subunit 1 phosphorylation
      (p-NR1) in the ipsilateral and contralateral spinal cord (L4-6), by Western
      blotting, to examine the superoxide-mediated central sensitization. Superoxide
      production was assessed by allopurinol-sensitive, XO-mediated lipid peroxidation
      of the spinal cord and gastrocnemius muscles. RESULTS: Withdrawal thresholds of
      forepaws did not vary across the 7 days of testing. In the hindpaws, both
      ipsilateral and contralateral mechanical allodynia was most attenuated in the BR
      group, followed by the BI and 3AR groups. The degree of NR1 activation was in
      contrast to the changes in the withdrawal thresholds. CONCLUSIONS: These data
      suggest that superoxide is involved in the development and maintenance of
      mechanical allodynia, particularly via central sensitization in the spinal cord.

PMID- 22949984
TI  - Wire-reinforced endotracheal tube fire during tracheostomy -A case report-.
AB  - Every operation could have a fire emergency, especially in the case of a
      tracheostomy. When a flammable gas meets a source of heat, the danger of fire is
      remarkable. A tracheal tube filled with a high concentration of oxygen is also a
      great risk factor for fire. Intra-tracheal tube fire is a rare, yet critical
      emergency with catastrophic consequences. Thus, numerous precautions are taken
      during a tracheostomy like, use of a special tube to prevent laser damage,
      ballooning of the tube with normal saline instead of air, and dilution of FiO(2)
      with helium or nitrogen. Since the first recorded cases on tube fires, most of
      the fires were initiated in the balloon and the tip. In the present case report,
      however, we came across a fire incidence, which originated from the wire.

PMID- 22949985
TI  - A case report of a carbon dioxide embolism caused by endoscopic vein harvesting
      during cardiac surgery -A case report-.
AB  - A carbon dioxide (CO(2)) embolism during endoscopic vein harvesting is a rare but
      potentially fatal complication. Early and accurate diagnosis is crucial for
      limiting the extent of the embolism and stabilizing the resulting cardiovascular
      compromise. We report a case of CO(2) embolization during endoscopic vein
      harvesting. Transesophageal echocardiography was instrumental in the diagnosis
      and management of this patient by further improving the decision making process,
      which resulted in the best outcome. Mid-esophageal bicaval view is the best view
      to determine whether a CO(2) embolism is coming from the upper or lower
      extremities.

PMID- 22949986
TI  - A case of diffuse alveolar hemorrhage after tonsillectomy -A case report-.
AB  - Diffuse alveolar hemorrhage (DAH) is an acute, life-threatening event. The blood
      gas barrier must be very thin to allow gas exchange and is therefore subjected to
      high mechanical stresses when the capillary pressure rises. In general
      anesthesia, inhaled gases cause high mechanical stresses, and thus DAH occurs
      under certain conditions. We describe a case of inferred postoperative DAH. A 25
      year-old man had an acute episode after undergoing a tonsillectomy for snoring.
      During surgery, no problems occurred and no marked bleeding was observed. After
      removal of the endotracheal tube, however, the patient had severe cough and
      hemoptysis. The patient was treated with an antihemorrhagic agent and
      antibiotics. He recovered after 1 week. Chronic snoring likely caused the
      alveolar damage in this patient and intubation led to DAH. The patient presented
      with a benign course that regressed spontaneously with medical intervention.

PMID- 22949987
TI  - Total intravenous anesthesia in a 10-month-old patient with congenital myotonic
      dystrophy undergoing endoscopic third ventriculostomy -A case report-.
AB  - Myotonic dystrophy is a rare genetic disorder characterized by muscle atrophy and
      weakness. Surgical treatment of this condition poses various problems for the
      anesthesiologist. We describe the anesthetic management of a 10-month-old infant
      with congenital myotonic dystrophy, who was scheduled for endoscopic third
      ventriculostomy under general anesthesia. Anesthesia was induced with thiopental
      sodium, fentanyl, and vecuronium, and thereafter maintained via continuous
      infusion of propofol and remifentanil. The train-of-four ratio was monitored
      throughout the operation, and muscle relaxation was reversed with pyridostigmine
      and glycopyrrolate at the end of the procedure. We show that total intravenous
      anesthesia using propofol and remifentanil is a satisfactory anesthetic technique
      in very young patients with congenital myotonic dystrophy.

PMID- 22949988
TI  - Seizure developed after palonosetron intravenous injection during recovery from
      general anesthesia -A case report-.
AB  - Seizure associated with antiemetics is rare. We report seizure associated with a
      5-HT(3) receptor antagonist in a 38 years old female. The patient underwent
      ureterorenoscopic lithotripsy due to left upper ureter stone. After operation,
      the patient complained of nausea in the postanesthetic recovery unit. In order to
      subside symptom, the patient was administrated 5-HT(3) receptor antagonist,
      palonosetron, 0.075 mg intravenously. Shortly after administration of that, the
      patient developed generalized tonic-clonic seizures. The symptom was subsided
      after midazolam and thiopental sodium were injected. But 40 minutes later,
      seizure recurred and subsided with midazolam again. The patient recovered
      completely without any specific sequelae.

PMID- 22949989
TI  - The use of laryngeal mask airway in pediatric patient with massive post
      tonsillectomy hemorrhage.

PMID- 22949990
TI  - Rhabdomyolysis in a chronic kidney disease patient after lung surgery.

PMID- 22949991
TI  - General anesthesia without neuromuscular blockade for a child with mitochondrial
      myopathy.

PMID- 22949992
TI  - Phrenic nerve palsy after internal jugular venous catheter placement.

PMID- 22949993
TI  - Current trends in the management of post-prostatectomy incontinence.
AB  - One of the annoying complications of radical prostatectomy is urinary
      incontinence. Post-prostatectomy incontinence (PPI) causes a significant impact
      on the patient's health-related quality of life. Although PPI is stress urinary
      incontinence caused by intrinsic sphincter deficiency in most cases, bladder
      dysfunction and vesicourethral anastomotic stenosis can induce urine leakage
      also. Exact clinical assessments, such as a voiding diary, incontinence
      questionnaire, pad test, urodynamic study, and urethrocystoscopy, are necessary
      to determine adequate treatment. The initial management of PPI is conservative
      treatment including lifestyle interventions, pelvic floor muscle training with or
      without biofeedback, and bladder training. An early start of conservative
      treatment is recommended during the first year. If the conservative treatment
      fails, surgical treatment is recommended. Surgical treatment of stress urinary
      incontinence after radical prostatectomy can be divided into minimally invasive
      and invasive treatments. Minimally invasive treatment includes injection of
      urethral bulking agents, male suburethral sling, and adjustable continence
      balloons. Invasive treatment includes artificial urinary sphincter implantation,
      which is still the gold standard and the most effective treatment of PPI.
      However, the demand for minimally invasive treatment is increasing, and many
      urologists consider male suburethral slings to be an acceptable treatment for
      PPI. The male sling is usually recommended for patients with persistent mild or
      moderate incontinence. It is necessary to improve our understanding of the
      pathophysiologic mechanisms of PPI and to compare different procedures for the
      development of new and potentially better treatment options.

PMID- 22949994
TI  - Cost aspects of radical nephrectomy for the treatment of renal cell carcinoma in
      Korea: open, laparoscopic, robot-assisted laparoscopic, and video-assisted
      minilaparotomy surgeries.
AB  - PURPOSE: This study aimed to comparatively evaluate the cost-effectiveness of
      four different types of radical nephrectomy (RN) techniques: open, laparoscopic,
      robot-assisted laparoscopic, and video-assisted minilaparotomy surgery (VAMS).
      MATERIALS AND METHODS: Among patients who were diagnosed with renal cell
      carcinoma and underwent RN, 20 patients were selected who received open,
      laparoscopic, robot-assisted laparoscopic, or VAMS RN between January 2008 and
      December 2010. Their medical fees were divided into four categories: procedure
      and operation, anesthesia, laboratory test, and medical supply fees. The medical
      costs of the patients were also divided into insured and uninsured costs.
      RESULTS: The total direct cost of VAMS, open, laparoscopic, and robot-assisted
      laparoscopic RN were 2,023,791+/-240,757, 2,024,246+/-674,859 (p=0.998),
      3,603,557+/-870,333 (p<0.01), and 8,021,902+/-330,157 (p<0.01) Korean Won (KRW,
      the currency of South Koea), respectively. The total insured cost of VAMS, open,
      laparoscopic, and robot-assisted laparoscopic RN was 1,904,627+/-231,957,
      1,798,127+/-645,602 (p=0.634), 3,039,769+/-711,792 (p<0.01), and 899,668+/
      323,508 (p<0.01) KRW, respectively. The total uninsured cost of VAMS, open,
      laparoscopic, and robot-assisted laparoscopic RN was 119,163+/-24,581, 226,119+/
      215,009, 563,788+/-487,798 (p<0.01), and 7,122,234+/-56,117 (p<0.01) KRW,
      respectively. Medical supply fees accounted for the largest portion of the costs
      and amounted to 33.43% of the VAMS cost. CONCLUSIONS: VAMS RN is as cost
      effective as open surgery. Furthermore, it is comparatively more cost-effective
      than laparoscopic and robot-assisted laparoscopic RN.

PMID- 22949995
TI  - Preoperative factors predictive of continence recovery after radical retropubic
      prostatectomy.
AB  - PURPOSE: We assessed the factors predictive of continence recovery after radical
      retropubic prostatectomy performed by use a single operative technique by a
      single surgeon. MATERIALS AND METHODS: Preoperative factors, including age, body
      mass index (BMI), prostate volume, prostate-specific antigen level, and
      anatomical information from preoperative magnetic resonance imaging (MRI), such
      as membranous urethral length, thickness of the levator ani muscle, and
      urogenital diaphragm, were evaluated in 94 consecutive patients who underwent
      radical retropubic prostatectomy between April 2005 and October 2010. Patients
      were also categorized into four different groups according to the overlying
      pattern of the prostatic apex and the membranous urethra. Continence status was
      evaluated by direct patient questioning at 12 months after the operation.
      RESULTS: The overall continence rate at 12 months after the operation was 79.8%.
      In the age- and BMI-adjusted logistic regression analysis, the membranous
      urethral length and the overlying pattern of the prostatic apex were significant
      predictive factors of the continence rate at 12 months after the operation
      (p=0.006 and p=0.007, respectively). Other predictive factors were not
      contributory. Patients with no overlapping observed between the prostatic apex
      and membranous urethra had longer membranous urethral lengths (14.24+/-2.73 mm)
      and higher rates of recovery of continence compared with other groups.
      CONCLUSIONS: Membranous urethral length and shape of the prostatic apex as
      assessed by preoperative MRI are significantly associated with recovery of
      urinary continence after radical retropubic prostatectomy.

PMID- 22949996
TI  - Differences in Postoperative Pathological Outcomes between Prostate Cancers
      Diagnosed at Initial and Repeat Biopsy.
AB  - PURPOSE: We evaluated the differences in pathological outcomes between prostate
      cancers (PCas) diagnosed at initial and repeat biopsy. MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of 287 patients who underwent
      radical retropubic prostatectomy from 2005 to 2010. We investigated preoperative
      factors, such as age, serum prostate-specific antigen (PSA), prostate volume
      (PV), digital rectal examination (DRE) results, biopsy schema, clinical stage,
      and number of prior biopsies, and postoperative pathological outcomes, including
      specimen volume, percent tumor volume, Gleason score (GS), tumor bilaterality,
      pathological stage, positive surgical margin (PSM), lymphovascular invasion
      (LVI), and perineural invasion (PNI). Patients were then classified into two
      groups by the number of prior biopsies (initial biopsy vs. repeat biopsy). We
      compared preoperative factors and postoperative pathological outcomes between the
      two groups. RESULTS: Of the 287 patients, 246 (85.7%) were diagnosed with cancer
      at the initial biopsy and 41 (14.3%) at the repeat biopsy. The repeat biopsy
      group was older (p=0.048), had a larger PV (p=0.009), had a significantly
      different biopsy schema (p<0.001), and had a lower (<10%) percentage tumor volume
      (p=0.016). In the multivariate analysis (after adjustment for biopsy schema, age,
      serum PSA, PV, and DRE), repeat biopsy was not an independent predictor of GS,
      tumor bilaterality, pathological stage, PSM, LVI, or PNI (p=0.212, 0.456, 0.459,
      0.917, 0.991 and 0.827, respectively), but repeat biopsy could predict lower
      percentage tumor volume (p=0.037). CONCLUSIONS: The pathological outcomes of PCas
      detected at repeat biopsy were not significantly different from those of PCas
      detected at initial biopsy except for a lower (<10%) percentage tumor volume.

PMID- 22949997
TI  - Advantages of robot-assisted laparoscopic radical prostatectomy in obese
      patients: comparison with the open procedure.
AB  - PURPOSE: Obesity has been suggested as a risk factor for worse perioperative
      outcomes, especially in radical prostatectomy, in several studies. However, the
      impact of obesity on perioperative outcomes has not yet been well elucidated for
      robot-assisted laparoscopic radical prostatectomy (RALP). We evaluated whether
      obesity had an adverse effect on outcomes following RALP compared with retropubic
      radical prostatectomy (RRP). MATERIALS AND METHODS: From April 2008 to May 2011,
      181 patients underwent radical prostatectomy (RALP, 111; RRP, 70). These patients
      were subdivided into two groups according to body mass index (BMI): the nonobese
      group (BMI, 25 kg/m(2) or less) and the obese group (BMI, greater than 25
      kg/m(2)). Perioperative outcomes in RALP and RRP were retrospectively compared
      between the two groups. RESULTS: In RRP, patients in the obese group (n=20)
      showed greater blood loss and a higher complication rate than did those in the
      nonobese group (n=50). However, in RALP, no statistically significant differences
      in perioperative outcomes were observed between the obese (n=37) and the nonobese
      (n=74) groups. RALP showed less blood loss and a lower complication rate in both
      the obese and nonobese groups than did RRP. CONCLUSIONS: RALP is thought to be a
      more effective and safer procedure in obese patients compared with traditional
      open radical prostatectomy. In the management of obese patients with localized
      prostate cancer, RALP should be considered as a primary choice for treatment.

PMID- 22949998
TI  - Analysis of the risk factors for overactive bladder on the basis of a survey in
      the community.
AB  - PURPOSE: To evaluate the risk factors for overactive bladder (OAB) in a
      population aged 40 years and over in the community. MATERIALS AND METHODS: We
      conducted a community-based survey of OAB in a population aged 40 years and over
      in Guri City and Yangpyeong County, South Korea, by use of the overactive bladder
      symptom score (OABSS) questionnaire. A total of 926 subjects were included in the
      final analysis. The definition of OAB was more than 2 points for the urgency
      score and 3 points for the sum of scores. In addition, the subjects were asked
      about age, dwelling place, marital status, educational status, behavioral factors
      (smoking, drinking, etc), and medical history. Categorical variables were
      analyzed by using the logistic regression model and were adjusted for age by
      using the logistic regression model. RESULTS: Overall OAB prevalence was 14.1%
      (130/926), made up of 49/403 males (12.2%) and 81/523 females (15.5%). OAB
      prevalence increased with age (p<0.0001). Risk factors for OAB were educational
      status (age-adjusted p=0.0487), stroke (p=0.0414), osteoporosis (p=0.0208),
      asthma (p=0.0091), rhinitis (p=0.0008), and cataract. Other factors (dwelling
      place, marital status, smoking, drinking, hypertension, diabetes, hyperlipidemia,
      myocardial infarction, angina, tuberculosis, atopic dermatitis, hepatitis B, and
      depression) were not associated with OAB. CONCLUSIONS: The prevalence of OAB in
      our study was about 14.1% and the risk factors for OAB were educational status,
      stroke, osteoporosis, asthma, rhinitis, and cataract. Knowledge of these risk
      factors may help in the diagnosis and treatment of OAB.

PMID- 22949999
TI  - Comparative Evaluation of Periprostatic Nerve Block with and without
      Intraprostatic Nerve Block in Transrectal Ultrasound-Guided Prostatic Needle
      Biopsy.
AB  - PURPOSE: Controversy exists over the pain during prostate biopsy. Periprostatic
      nerve block is a commonly used anaesthetic technique during transrectal
      ultrasound (TRUS)-guided prostate biopsy. The recent trend toward increasing the
      number of cores has become popular. This practice further increases the need for
      a proper anaesthetic application. We compared the efficacy of periprostatic nerve
      block with or without intraprostatic nerve block. MATERIALS AND METHODS: We
      conducted a prospective double-blinded placebo-controlled study at our institute
      with 142 consecutive patients. Patients were randomly assigned into 3 groups.
      Group 1 received periprostatic nerve block with intraprostatic nerve block with
      1% lignocaine. Group 2 patients were administered periprostatic nerve block only
      with 1% lignocaine. Group 3 received no anaesthesia. Patients were asked to grade
      their level of pain by using an 11-point linear analogue scale at the time of
      ultrasound probe insertion, at the time of anaesthesia, during biopsy, and 30
      minutes after biopsy. RESULTS: The study groups were comparable in demographic
      profile, prostate-specific antigen (PSA) level, and prostate size. The mean pain
      scores at the time of biopsy in groups 1, 2, and 3 were 2.70, 3.39, and 4.16,
      respectively. Group 1 recorded the minimum mean pain score of 2.70 during
      prostate biopsy, which was significantly lower than the scores of groups 2 and 3
      (p<0.001). There were no significant differences in pain scores among the 3
      groups during probe insertion, during anaesthesia, or at 30 minutes after biopsy
      (p>0.05). CONCLUSIONS: Periprostatic nerve block with intraprostatic nerve block
      provides better pain control than does periprostatic nerve block alone in TRUS
      guided prostate biopsy.

PMID- 22950000
TI  - Analysis of changes in the glomerular filtration rate as measured by the cockroft
      gault formula in the early period after percutaneous nephrolithotomy.
AB  - PURPOSE: We aimed to analyze the changes in kidney function during the
      postoperative early period caused by the application of percutaneous
      nephrolithotomy (PNL), which is commonly used in kidney stone surgery. MATERIALS
      AND METHODS: PNL was performed in 80 patients (48 men, 32 women) with kidney
      stones. The mean age of the patients was 43.71 years (range, 18 to 71 years).
      Preoperative and postoperative values for stone size, glomerular filtration rate
      (GFR), serum creatinine, urea, electrolytes (Na, K, Cl), and Hb were compared in
      80 patients in whom PNL surgery was performed. The formula of Cockroft-Gault was
      used to calculate the GFR during the early postoperative period (72 to 96 hours).
      RESULTS: Statistically significant decreases after PNL were observed in average
      stone size (preoperative, 627.75+/-375.10 mm(2); postoperative, 81.70+/-16.15
      mm(2)), serum urea (preoperative, 38.40+/-17.26 mg/dl; postoperative, 33.28+/
      16.98 mg/dl), and creatinine (preoperative, 1.03+/-0.53 mg/dl; postoperative,
      0.97+/-0.55 mg/dl) and an increase was observed in GFR (preoperative, 104.30+/
      37.30 ml/min; postoperative, 112.38+/-40.1 ml/min). No changes were detected in
      the serum electrolyte values (Na, K, Cl). Multiple access, operation time, and
      type of lithotripter did not have any significant effects on the change in the
      GFR. CONCLUSIONS: In light of our results, PNL for kidney stone operations
      appears to be a reliable and efficient method that provides recovery of kidney
      functions in the early post-operative period by increasing the GFR and with high
      stone-free rates.

PMID- 22950001
TI  - Isolation and characterization of smooth muscle cells from rat corpus cavernosum
      tissue for the study of erectile dysfunction.
AB  - PURPOSE: Primary culture of the cavernous smooth muscle cells from corpus
      cavernous tissues is known to be difficult, mainly because of contamination with
      fibroblasts. We applied a new method for better isolation of rat penile smooth
      muscle cells (RPSMCs) from rat corpus cavernosum tissue for reliable ex vivo
      research on erectile dysfunction. MATERIALS AND METHODS: With the use of 8-week
      old adult male Sprague-Dawley rats, ex vivo migrations of rat cavernous tissue
      were measured by penis and aortic ring assay by use of a Matrigel-based D-valine
      modified culture method. The expression of alpha-smooth muscle actin (alpha-SMA)
      and platelet/endothelial cell adhesion molecule (PECAM)-1 in the RPSMCs was
      determined by standard immunofluorescent staining and immunoblotting. The
      expression patterns of phosphodiesterase (PDE) family mRNA in RPSMCs were
      compared with patterns in rat aortic smooth muscle cells (RASMCs) by use of
      quantitative real-time reverse transcription polymerase chain reaction. RESULTS:
      Immunocytochemical staining showed greater alpha-SMA-positive and PCAM-1-negative
      fluorescence. Moreover, whereas the expression of alpha-SMA was detected in the
      RPSMCs, that of PECAM-1 was not. The levels of PDE1A, PDE1B, PDE1C, PDE2A, PDE3A,
      PDE4A, PDE4B, PDE4C, PDE4D, and PDE5A mRNA in the RPSMCs were about 3.2-, 4.4-,
      3.4-, 29.0-, 3.5-, 2.8-, 2.9-, 6.1-, 45.0-, and 6.0-fold the corresponding
      expression in RASMCs. CONCLUSIONS: We developed a two-stage tissue culture method
      utilizing a Matrigel-based sprouting culture system to facilitate stromal cell
      sprouting and an adherent culture system using D-valine to eliminate the
      contamination of fibroblasts into the smooth muscle cells.

PMID- 22950002
TI  - Comparison of Surgical Outcomes between Dismembered Pyeloplasty with or without
      Ureteral Stenting in Children with Ureteropelvic Junction Obstruction.
AB  - PURPOSE: To evaluate the impact of temporary internal ureteral stents on the
      surgical outcomes of dismembered pyeloplasty in children. MATERIALS AND METHODS:
      The medical records of 70 children (76 renal units) who underwent dismembered
      pyeloplasty for ureteropelvic junction (UPJ) obstruction at at Asan Medical
      Center between January 2005 and December 2010 were retrospectively reviewed. We
      classified the renal units into the stented group (22 renal units) and the
      nonstented group (54 renal units). Fifty-four of 70 patients were male and their
      mean age was 2.2+/-3.8 years old. The mean follow-up period was 29.6+/-16.8
      months. RESULTS: Sixty-four children had unilateral UPJ obstruction. The mean
      stent duration was 31.9 days. As shown by evaluation of radiologic images, there
      were no significant differences between the stented group and the nonstented
      group during the follow-up period (p>0.05). The mean preoperative and
      postoperative anteroposterior pelvic diameters (APPDs) of the nonstented group
      were 31.3 mm and 15.1 mm, respectively (p<0.001). The preoperative and
      postoperative grades of hydronephrosis were 3.9 and 2.9, respectively (p=0.037).
      The mean preoperative and postoperative APPDs of the stented group were 36.4 mm
      and 15.6 mm, respectively (p<0.001). The preoperative and postoperative grades of
      hydronephrosis were 4 and 3.1, respectively (p<0.001). Repeat obstruction was
      shown in 4 subjects as a postoperative complication (5.7%). Two children from
      each group had recurrent UPJ obstruction, with percentages of 3.7% and 9%,
      respectively (p=0.575). CONCLUSIONS: In a comparison of nonstented and stented
      groups during pediatric dismembered pyeloplasty for UPJ obstruction, no
      significant differences were found in the resolution of hydronephrosis or overall
      postoperative complications.

PMID- 22950003
TI  - Comparison of immediate primary repair and delayed urethroplasty in men with
      bulbous urethral disruption after blunt straddle injury.
AB  - PURPOSE: The aim of this study was to analyze the outcomes of immediate primary
      repair (IPR) compared with delayed repair (DR) after initial suprapubic
      cystostomy. MATERIALS AND METHODS: We reviewed the records of 60 patients with
      bulbous urethral disruption after blunt trauma from February 2001 to March 2011.
      Seventeen patients who presented in an acute injury state underwent IPR; 43
      patients underwent DR after the initial suprapubic cystostomy. None of the
      patients had undergone previous urethral manipulation. We compared the outcomes,
      including stricture, impotence, and incontinence, between the two management
      approaches. We also measured the time to spontaneous voiding, the duration of
      suprapubic diversion, and the number of days spent in the hospital. RESULTS: The
      median follow-up was 20.5 months (range, 13 to 59 months; mean, 23.3 months).
      Among 17 patients in the IPR group, strictures developed in 2 patients (11.7%),
      and among 53 patients in the DR group, strictures developed in 8 patients (18.6%,
      p=0.709). The incidences of impotence and incontinence were similar in both
      groups (17.6% and 0% in the IPR group vs. 27.9% and 4.6% in the DR group, p=0.520
      and 1.000, respectively). The time to spontaneous voiding and the duration of
      suprapubic diversion were significantly shorter in the IPR group (average 27.3
      and 33.4 days, respectively) than in the DR group (average 191.6 and 198.1 days,
      respectively; p<0.001 and <0.001). CONCLUSIONS: IPR may provide comparable
      outcomes to DR and allow for shorter times to spontaneous voiding and reduce the
      duration of suprapubic diversion.

PMID- 22950004
TI  - Category migration of renal cystic masses with use of gadolinium-enhanced
      magnetic resonance imaging.
AB  - The Bosniak renal cyst classification has been accepted by urologists and
      radiologists as a way of diagnosing cystic renal masses and determining the
      management approach. We report two cases of a renal cystic mass that showed a
      category change from category II on the basis of enhanced computed tomography to
      category IV after further gadolinium-enhanced magnetic resonance imaging. In both
      cases, the cysts were later confirmed as kidney cancer by pathology.

PMID- 22950005
TI  - Wilms' tumor in a horseshoe kidney.
AB  - The incidence of horseshoe kidney is about 1 in 400 cases. The presence of Wilms'
      tumor with a horseshoe kidney is unusual, and the occurrence of Wilms' tumor in a
      horseshoe kidney is estimated at 0.4 to 0.9% of all Wilms' tumors. We report the
      case of a 5-year-old boy who presented with a stage IV Wilms' tumor in a
      horseshoe kidney. The patient was treated with preoperative chemotherapy followed
      by surgical resection and adjuvant chemotherapy. This case illustrates the role
      of preoperative chemotherapy for preserving renal function and aims to highlight
      the multimodality treatment of Wilms' tumor.

PMID- 22950006
TI  - Opening new perspectives on microbiology.

PMID- 22950007
TI  - Isolation of a novel Saccharophagus species (Myt-1) capable of degrading a
      variety of seaweeds and polysaccharides.
AB  - A bacterial strain, Myt-1, was isolated in Toyama Bay in Toyama Prefecture,
      Japan. Myt-1 was capable of reducing the thalli of various seaweed species to
      single cell detritus particles. A 16S rDNA homology search revealed that the
      closest relative of Myt-1 was Saccharophagus degradans 2-40 (CP000282; 100%
      similarity), which was first isolated in Chesapeake Bay in Virginia, USA. The Myt
      1 strain was capable of degrading more than 10 polysaccharides, almost all of
      which were also degraded by S. degradans 2-40. Analyses of alginase gene DNA
      sequence homology, DNA-DNA homology, and zymogram analysis of obtained
      polysaccharidases suggested that Myt-1 was a new species of Saccharophagus. Thus,
      Myt-1 is only the second species in this genus, which has contained only one
      strain and species since 1988, and was tentatively designated Saccharophagus sp.
      Myt-1. Myt-1 has considerable potential for reducing the volume of seaweed
      wastes, and for producing functional materials from seaweed substrate.

PMID- 22950008
TI  - Importance of the latex-clearing protein (Lcp) for poly(cis-1,4-isoprene) rubber
      cleavage in Streptomyces sp. K30.
AB  - Streptomyces sp. strain K30 induces the formation of an extracellular Lcp (latex
      clearing protein) during poly(cis-1,4-isoprene) degradation. To investigate the
      function of this enzyme in Streptomyces sp. strain K30, the lcp gene was
      disrupted. This was the first time that the screening for a knock out lcp mutant
      of Streptomyces sp. strain K30 was successful. The resulting mutant Streptomyces
      sp. K30_lcpOmegaKm exhibited reduced growth in liquid mineral salts media
      containing poly(cis-1,4-isoprene) as the sole carbon and energy source.
      Additionally, there was no detectable Lcp activity on latex overlay agar plates.
      When Lcp from Streptomyces sp. strain K30 was heterologously expressed in strains
      TK23 and TK24 of Streptomyces lividans and a strain of S. erythraea with plasmid
      pIJ6021::lcp, the recombinant strains acquired the ability to cleave synthetic
      poly(cis-1,4-isoprene), confirming the involvement of Lcp in initial polymer
      cleavage. Specific anti-LcpK30 IgGs were employed in Western blot analysis to
      detect the secretion of Lcp in the supernatant. We have conducted an important
      experiment to demonstrate Lcp activity using the supernatant of these Lcp
      expressing strains in vitro. All three strains obviously secreted a functional
      Lcp, as indicated by the formation of halo. Functional testing of Lcp with
      different plasmids in Escherichia coli strains and Pseudomonas strains was,
      however, not successful.

PMID- 22950009
TI  - Identification of a five-oxidoreductase-gene cluster from Acetobacter
      pasteurianus conferring ethanol-dependent acidification in Escherichia coli.
AB  - Acetobacter pasteurianus, a Gram-negative bacterium belonging to the alpha
      divison of Proteobacteria, produces acetic acid through ethanol oxidation. A
      genomic bank of A. pasteurianus 386B DNA was cloned in the low-copy cosmid
      pRG930Cm vector and the resulting clones were screened for the production of
      protease using the skimmed-milk agar assay whereby a clearing zone around the
      inoculated spots indicates casein degradation. Several positive clones were
      selected and restriction analysis revealed that many contained the same inserts.
      One clone was further analyzed and the cosmid DNA subjected to in vitro
      transposon insertion. After electroporation, several clones having lost the
      capacity to cause casein degradation were isolated and the sequence of the
      transposon-flanking regions analyzed. The majority of insertions mapped to one
      gene encoding an NAD(P)(+)-dependent aldehyde dehydrogenase (ALDH) of the PNTB
      superfamily, whereas one insert was found upstream in a gene encoding an ethanol
      dehydrogenase. Addition of phenol red to the medium confirmed the ethanol
      dependent acidification around the inoculated spots of the clones without
      transposon insertion, suggesting that casein degradation is due to the production
      of acetic acid as a result of the combined activities of the alcohol
      dehydrogenase and ALDH. Quantitative data and pH measurements confirmed a
      significant acidification, and the presence of acetic acid.

PMID- 22950010
TI  - XatA, an AT-1 autotransporter important for the virulence of Xylella fastidiosa
      Temecula1.
AB  - Xylella fastidiosa Temecula1 is the causative agent of Pierce's disease of
      grapevine, which is spread by xylem-feeding insects. An important feature of the
      infection cycle is the ability of X. fastidiosa to colonize and interact with two
      distinct environments, the xylem of susceptible plants and the insect foregut.
      Here, we describe our characterization of XatA, the X. fastidiosa autotransporter
      protein encoded by PD0528. XatA, which is classified as an AT-1 (classical)
      autotransporter, has a C-terminal beta-barrel domain and a passenger domain
      composed of six tandem repeats of approximately 50 amino acids. Localization
      studies indicate that XatA is present in both the outer membrane and membrane
      vesicles and its passenger domain can be found in the supernatant. Moreover, XatA
      is important for X. fastidiosa autoaggregation and biofilm formation based on
      mutational analysis and the discovery that Escherichia coli expressing XatA
      acquire these traits. The xatA mutant also shows a significant decrease in
      Pierce's disease symptoms when inoculated into grapevines. Finally, X. fastidiosa
      homologs to XatA, which can be divided into three distinct groups based on
      synteny, form a single, well-supported clade, suggesting that they arose from a
      common ancestor.

PMID- 22950011
TI  - Antimicrobial metallic copper surfaces kill Staphylococcus haemolyticus via
      membrane damage.
AB  - Recently, copper (Cu) in its metallic form has regained interest for its
      antimicrobial properties. Use of metallic Cu surfaces in worldwide hospital
      trials resulted in remarkable reductions in surface contaminations. Yet, our
      understanding of why microbes are killed upon contact to the metal is still
      limited and different modes of action have been proposed. This knowledge,
      however, is crucial for sustained use of such surfaces in hospitals and other
      hygiene-sensitive areas. Here, we report on the molecular mechanisms by which the
      Gram-positive Staphylococcus haemolyticus is inactivated by metallic Cu.
      Staphylococcus haemolyticus was killed within minutes on Cu but not on stainless
      steel demonstrating the antimicrobial efficacy of metallic Cu. Inductively
      coupled plasma mass spectroscopy (ICP-MS) analysis and in vivo staining with
      Coppersensor-1 indicated that cells accumulated large amounts of Cu ions from
      metallic Cu surfaces contributing to lethal damage. Mutation rates of Cu- or
      steel-exposed cells were similarly low. Instead, live/dead staining indicated
      cell membrane damage in Cu- but not steel-exposed cells. These findings support a
      model of the cellular targets of metallic Cu toxicity in bacteria, which suggests
      that metallic Cu is not genotoxic and does not kill via DNA damage. In contrast,
      membranes constitute the likely Achilles' heel of Cu surface-exposed cells.

PMID- 22950012
TI  - Short-term effects of temperature on the abundance and diversity of magnetotactic
      cocci.
AB  - Temperature is one of the most important climate factors that can regulate the
      activity and growth of organisms. However, it is so far unclear how temperature
      influences the abundance and community composition of magnetotactic bacteria
      (MTB) that mineralize intracellular magnetite and/or greigite magnetosomes and
      play significant roles in the global iron cycling and sediment magnetization. To
      address this specific problem, in this study we have assessed the impact of
      temperature on freshwater magnetotactic cocci through laboratory microcosm
      simulations. Microcosms containing MTB were exposed to four constant temperatures
      ranging from 9 degrees C to 37 degrees C. After 10 days and 28 days of
      incubation, no significant differences in abundance were detected in microcosms
      at 9 degrees C, 15 degrees C, and 26 degrees C (Student's t-test, P > 0.05);
      however, microcosms exposed to 37 degrees C exhibited a significant decrease of
      magnetotactic cocci abundance (P < 0.05). Dendrogram analysis of community
      amplified ribosomal DNA restriction analysis (community ARDRA) banding patterns
      distinguished the 37 degrees C samples from samples at lower temperatures
      regardless of incubation periods. Furthermore, clone library analysis revealed
      that most of the operational taxonomic units (OTUs) detected in samples from 9
      degrees C to 26 degrees C were absent from the 37 degrees C microcosms, whereas
      six OTUs were exclusively detected in the 37 degrees C samples. Community
      compositions from four incubation temperatures were further compared using
      statistical phylogenetic methods (UniFrac and LIBSHUFF), which revealed that the
      37 degrees C samples harbored phylogenetically distinct MTB communities compared
      to those found in 9 degrees C, 15 degrees C, and 26 degrees C samples. Taken
      together, our results indicate that elevated temperature can influence the
      abundance and diversity of dominant members of magnetotactic cocci. This linkage
      further infers that the abundance and diversity of MTB (e.g., based on the fossil
      magnetosomes) may be useful in reconstruction of paleotemperature.

PMID- 22950013
TI  - Comparison of Scheffersomyces stipitis strains CBS 5773 and CBS 6054 with regard
      to their xylose metabolism: implications for xylose fermentation.
AB  - The various strains of Scheffersomyces stipitis (Pichia stipitis) differ
      substantially with respect to their ability to ferment xylose into ethanol. Two
      P. stipitis strains CBS 5773 and CBS 6054 have been most often used in literature
      but comparison of their performance in xylose fermentation under identical
      conditions has not been reported so far. Conversion of xylose (22 g/L) by each of
      these P. stipitis strain was analyzed under anaerobic and microaerobic
      conditions. Ethanol yields of ~0.41 g/g were independent of strain and conditions
      used. Glycerol and acetate were formed in constant yields of 0.006 g/g and 0.02
      g/g, respectively. Xylitol formation decreased from ~0.08 g/g to ~0.05 g/g upon
      switch from anaerobic to microaerobic conditions. Specific activities of enzymes
      of the two-step oxidoreductive xylose conversion pathway (xylose reductase and
      xylitol dehydrogenase) matched for both strains within limits of error. When
      xylose was offered at 76 g/L under microaerobic reaction conditions, ethanol
      yields were still high (0.37-0.39 g/g) for both strains even though the xylitol
      yields (0.12-0.13 g/g) were increased as compared to the conditions of low xylose
      concentration. P. stipitis strains CBS 5773 and CBS 6054 are therefore identical
      by the criteria selected and show useful performance during conversion of xylose
      into ethanol, irrespective of the supply of oxygen.

PMID- 22950014
TI  - The C-tail anchored TssL subunit, an essential protein of the enteroaggregative
      Escherichia coli Sci-1 Type VI secretion system, is inserted by YidC.
AB  - Type VI secretion systems (T6SS) are macromolecular complexes present in Gram
      negative bacteria. T6SS are structurally similar to the bacteriophage cell
      puncturing device and have been shown to mediate bacteria-host or bacteria
      bacteria interactions. T6SS assemble from 13 to 20 proteins. In enteroaggregative
      Escherichia coli (EAEC), one of the subassemblies is composed of four proteins
      that form a trans-envelope complex: the TssJ outer membrane lipoprotein, the
      peptidoglycan-anchored inner membrane TagL protein, and two putative inner
      membrane proteins, TssL and TssM. In this study, we characterized the TssL
      protein of the EAEC Sci-1 T6SS in terms of localization, topology, and function.
      TssL is a critical component of the T6SS, anchored to the inner membrane through
      a single transmembrane segment located at the extreme C-terminus of the protein.
      We further show that this transmembrane segment is essential for the function of
      the protein and its proper insertion in the inner membrane is dependent upon YidC
      and modulated by the Hsp70 homologue DnaK.

PMID- 22950016
TI  - Eukaryotic life in biofilms formed in a uranium mine.
AB  - The underground uranium mine Konigstein (Saxony, Germany), currently in the
      process of remediation, represents an underground acid mine drainage (AMD)
      environment, that is, low pH conditions and high concentrations of heavy metals
      including uranium, in which eye-catching biofilm formations were observed. During
      active uranium mining from 1984 to 1990, technical leaching with sulphuric acid
      was applied underground on-site resulting in a change of the underground mine
      environment and initiated the formation of AMD and also the growth of AMD-related
      copious biofilms. Biofilms grow underground in the mine galleries in a depth of
      250 m (50 m above sea level) either as stalactite-like slime communities or as
      acid streamers in the drainage channels. The eukaryotic diversity of these
      biofilms was analyzed by microscopic investigations and by molecular methods,
      that is, 18S rDNA PCR, cloning, and sequencing. The biofilm communities of the
      Konigstein environment showed a low eukaryotic biodiversity and consisted of a
      variety of groups belonging to nine major taxa: ciliates, flagellates, amoebae,
      heterolobosea, fungi, apicomplexa, stramenopiles, rotifers and arthropoda, and a
      large number of uncultured eukaryotes, denoted as acidotolerant eukaryotic
      cluster (AEC). In Konigstein, the flagellates Bodo saltans, the stramenopiles
      Diplophrys archeri, and the phylum of rotifers, class Bdelloidea, were detected
      for the first time in an AMD environment characterized by high concentrations of
      uranium. This study shows that not only bacteria and archaea may live in
      radioactive contaminated environments, but also species of eukaryotes, clearly
      indicating their potential influence on carbon cycling and metal immobilization
      within AMD-affected environment.

PMID- 22950017
TI  - Human mitochondrial ferritin improves respiratory function in yeast mutants
      deficient in iron-sulfur cluster biogenesis, but is not a functional homologue of
      yeast frataxin.
AB  - We overexpressed human mitochondrial ferritin in frataxin-deficient yeast cells
      (Deltayfh1), but also in another mutant affected in [Fe-S] assembly (Deltaggc1).
      Ferritin was correctly processed and expressed in the mitochondria of these
      cells, but the fraction of total mitochondrial iron bound to ferritin was very
      low, and most of the iron remained in the form of insoluble particles of ferric
      phosphate in these mitochondria, as evidenced by gel filtration analysis of the
      mitochondrial matrix (fast protein liquid chromatography [FPLC]) and by Mossbauer
      spectroscopy. Mutant cells in which ferritin was overexpressed still accumulated
      iron in the mitochondria and remained deficient in [Fe-S] assembly, suggesting
      that human mitochondrial ferritin is not a functional homologue of yeast
      frataxin. However, the respiratory function was improved in these mutants, which
      correlates with an improvement of cytochrome and heme synthesis. Overexpression
      of mitochondrial ferritin in [Fe-S] mutants resulted in the appearance of a small
      pool of high-spin ferrous iron in the mitochondria, which was probably
      responsible for the improvement of heme synthesis and of the respiratory function
      in these mutants.

PMID- 22950018
TI  - Zinc-responsive coactivator recruitment by the yeast Zap1 transcription factor.
AB  - The zinc-responsive Zap1 transcription factor of Saccharomyces cerevisiae
      controls many genes involved in zinc homeostasis. Zap1 has two activation
      domains, AD1 and AD2, which are independently regulated by zinc. While AD1 can
      fully activate most Zap1 target genes, AD2 is active only on a subset of those
      genes. One hypothesis explaining this promoter specificity was that AD1 and AD2
      recruit different coactivators. To address this question, we carried out a
      genetic screen to identify coactivator complexes that are required for Zap1
      mediated activation. SWI/SNF, SAGA, and Mediator complexes were implicated as
      playing major roles in Zap1 activation. Consistent with this conclusion, we found
      that these three complexes are recruited to Zap1 target promoters in a zinc
      responsive and Zap1-dependent manner. Coactivator recruitment was highly
      interdependent such that mutations disrupting SAGA impaired recruitment of
      SWI/SNF and vice versa. Optimal Mediator recruitment was dependent on both SAGA
      and SWI/SNF. A comparison of the coactivators recruited by AD1 and AD2 found no
      obvious differences suggesting that recruitment of different coactivators is not
      likely the mechanism of AD specificity. Rather, our results suggest that AD2
      recruits coactivators less effectively than AD1 and is therefore only functional
      on some promoters.

PMID- 22950019
TI  - Expression of a small (p)ppGpp synthetase, YwaC, in the (p)ppGpp(0) mutant of
      Bacillus subtilis triggers YvyD-dependent dimerization of ribosome.
AB  - To elucidate the biological functions of small (p)ppGpp synthetases YjbM and YwaC
      of Bacillus subtilis, we constructed RIK1059 and RIK1066 strains carrying
      isopropyl-beta-D-thiogalactopyranoside (IPTG) inducible yjbM and ywaC genes,
      respectively, in the DeltarelA DeltayjbM DeltaywaC triple mutant background.
      While the uninduced and IPTG-induced RIK1059 cells grew similarly in LB medium,
      the growth of RIK1066 cells was arrested following the addition of IPTG during
      the early exponential growth phase. Induction of YwaC expression by IPTG also
      severely decreased the intracellular GTP level and drastically altered the
      transcriptional profile in RIK1066 cells. Sucrose density gradient centrifugation
      analysis of the ribosomal fractions prepared from the IPTG-induced RIK1066 cells
      revealed three peaks corresponding to 30S, 50S, and 70S ribosome particles, and
      also an extra peak. Electron microscope studies revealed that the extra peak
      fraction contained dimers of 70S ribosomes, which were similar to the Escherichia
      coli 100S ribosomes. Proteomic analysis revealed that the 70S dimer contained an
      extra protein, YvyD, in addition to those found in the 70S ribosome. Accordingly,
      strain resulting from the disruption of the yvyD gene in the RIK1066 cells was
      unable to form 70S dimers following IPTG induction, indicating that YvyD is
      required for the formation of these dimers in B. subtilis.

PMID- 22950021
TI  - Identification of a putative glycosyltransferase responsible for the transfer of
      pseudaminic acid onto the polar flagellin of Aeromonas caviae Sch3N.
AB  - Motility in Aeromonas caviae, in a liquid environment (in broth culture), is
      mediated by a single polar flagellum encoded by the fla genes. The polar
      flagellum filament of A. caviae is composed of two flagellin subunits, FlaA and
      FlaB, which undergo O-linked glycosylation with six to eight pseudaminic acid
      glycans linked to serine and threonine residues in their central region. The flm
      genetic locus in A. caviae is required for flagellin glycosylation and the
      addition of pseudaminic acid (Pse) onto the lipopolysaccharide (LPS) O-antigen.
      However, none of the flm genes appear to encode a candidate glycotransferase that
      might add the Pse moiety to FlaA/B. The motility-associated factors (Maf
      proteins) are considered as candidate transferase enzymes, largely due to their
      conserved proximity to flagellar biosynthesis loci in a number of pathogens.
      Bioinformatic analysis performed in this study indicated that the genome of A.
      caviae encodes a single maf gene homologue (maf1). A maf mutant was generated and
      phenotypic analysis showed it is both nonmotile and lacks polar flagella. In
      contrast to flm mutants, it had no effect on the LPS O-antigen pattern and has
      the ability to swarm. Analysis of flaA transcription by reverse transcriptase PCR
      (RT-PCR) showed that its transcription was unaltered in the maf mutant while a
      His-tagged version of the FlaA flagellin protein produced from a plasmid was
      detected in an unglycosylated intracellular form in the maf strain.
      Complementation of the maf strain in trans partially restored motility, but
      increased levels of glycosylated flagellin to above wild-type levels.
      Overexpression of maf inhibited motility, indicating a dominant negative effect,
      possibly caused by high amounts of glycosylated flagellin inhibiting assembly of
      the flagellum. These data provide evidence that maf1, a pseudaminyl transferase,
      is responsible for glycosylation of flagellin and suggest that this event occurs
      prior to secretion through the flagellar Type III secretion system.

PMID- 22950020
TI  - Diversity of Bacteria and Archaea in hypersaline sediment from Death Valley
      National Park, California.
AB  - The objective of this study was to phylogenetically analyze microorganisms from
      the domains Bacteria and Archaea in hypersaline sediment from Death Valley
      National Park. Using domain-specific primers, a region of the 16S rRNA gene was
      amplified using polymerase chain reaction (PCR), and the product was subsequently
      used to create a clone library. A total of 243 bacterial clones, 99 archaeal
      clones, and 209 bacterial isolates were examined. The 243 clones from Bacteria
      were affiliated with the following groups: the Bacilli (59 clones) and Clostridia
      (1) of the Firmicutes, Bacteroidetes (90), Proteobacteria (27), Cyanobacteria
      (18), Gemmatimonadetes (41), candidate division OP1 (5), Actinobacteria (1), and
      the Deinococcus-Thermus division (1). Within the class Bacilli, 46 of 59 clones
      were tentatively identified as 10 unclassified species. The majority of bacterial
      isolates (130 of 209) were more closely related to the Bacillus subtilis-B.
      licheniformis clade than to any other recognized taxon, and an Ecotype Simulation
      analysis of B. subtilis relatives identified four previously unknown ecotypes.
      Several new genera were discovered within the Bacteroidetes (4) and the
      Gemmatimonadetes (2). Of the 99 archaeal clones, 94 were tentatively identified
      as belonging to 3 new genera within the Halobacteriaceae; other clones
      represented novel species within each of 4 established genera.

PMID- 22950022
TI  - Debaryomyces hansenii strains differ in their production of flavor compounds in a
      cheese-surface model.
AB  - Flavor production among 12 strains of Debaryomyces hansenii when grown on a
      simple cheese model mimicking a cheese surface was investigated by dynamic
      headspace sampling followed by gas chromatography-mass spectrometry. The present
      study confirmed that D. hansenii possess the ability to produce important cheese
      flavor compounds, primarily branched-chain aldehydes and alcohols, and thus
      important for the final cheese flavor. Quantification of representative aldehydes
      (2-Methylpropanal, 3-Methylbutanal) and alcohols (2-Methyl-1-propanol, 3-Methyl-1
      butanol, and 3-Methyl-3-buten-1-ol) showed that the investigated D. hansenii
      strains varied significantly with respect to production of these flavor
      compounds. Contrary to the alcohols (2-Methyl-1-propanol, 3-Methyl-1-butanol, and
      3-Methyl-3-buten-1-ol), the aldehydes (2-Methylpropanal, 3-Methylbutanal) were
      produced by the D. hansenii strains in concentrations higher than their sensory
      threshold values, and thus seemed more important than alcohols for cheese flavor.
      These results show that D. hansenii strains may have potential to be applied as
      cultures for increasing the nutty/malty flavor of cheese due to their production
      of aldehydes. However, due to large strain variations, production of flavor
      compounds has to be taken into consideration for selection of D. hansenii strains
      as starter cultures for cheese production.

PMID- 22950023
TI  - A theoretical and experimental proteome map of Pseudomonas aeruginosa PAO1.
AB  - A total proteome map of the Pseudomonas aeruginosa PAO1 proteome is presented,
      generated by a combination of two-dimensional gel electrophoresis and protein
      identification by mass spectrometry. In total, 1128 spots were visualized, and
      181 protein spots were characterized, corresponding to 159 different protein
      entries. In particular, protein chaperones and enzymes important in energy
      conversion and amino acid biosynthesis were identified. Spot analysis always
      resulted in the identification of a single protein, suggesting sufficient spot
      resolution, although the same protein may be detected in two or more neighboring
      spots, possibly indicating posttranslational modifications. Comparison to the
      theoretical proteome revealed an underrepresentation of membrane proteins, though
      the identified proteins cover all predicted subcellular localizations and all
      functional classes. These data provide a basis for subsequent comparative studies
      of the biology and metabolism of P. aeruginosa, aimed at unraveling global
      regulatory networks.

PMID- 22950024
TI  - Adaptation to potassium starvation of wild-type and K(+)-transport mutant
      (trk1,2) of Saccharomyces cerevisiae: 2-dimensional gel electrophoresis-based
      proteomic approach.
AB  - Saccharomyces cerevisiae wild-type (BY4741) and the corresponding mutant lacking
      the plasma membrane main potassium uptake systems (trk1,trk2) were used to
      analyze the consequences of K(+) starvation following a proteomic approach. In
      order to trigger high-affinity mode of potassium transport, cells were
      transferred to potassium-free medium. Protein profile was followed by two
      dimensional (2-D) gels in samples taken at 0, 30, 60, 120, 180, and 300 min
      during starvation. We observed a general decrease of protein content during
      starvation that was especially drastic in the mutant strain as it was the case of
      an important number of proteins involved in glycolysis. On the contrary, we
      identified proteins related to stress response and alternative energetic
      metabolism that remained clearly present. Neural network-based analysis indicated
      that wild type was able to adapt much faster than the mutant to the stress
      process. We conclude that complete potassium starvation is a stressful process
      for yeast cells, especially for potassium transport mutants, and we propose that
      less stressing conditions should be used in order to study potassium homeostasis
      in yeast.

PMID- 22950025
TI  - Extracytoplasmic function sigma factors of the widely distributed group ECF41
      contain a fused regulatory domain.
AB  - Bacteria need signal transducing systems to respond to environmental changes.
      Next to one- and two-component systems, alternative sigma factors of the extra
      cytoplasmic function (ECF) protein family represent the third fundamental
      mechanism of bacterial signal transduction. A comprehensive classification of
      these proteins identified more than 40 phylogenetically distinct groups, most of
      which are not experimentally investigated. Here, we present the characterization
      of such a group with unique features, termed ECF41. Among analyzed bacterial
      genomes, ECF41 sigma factors are widely distributed with about 400 proteins from
      10 different phyla. They lack obvious anti-sigma factors that typically control
      activity of other ECF sigma factors, but their structural genes are often
      predicted to be cotranscribed with carboxymuconolactone decarboxylases,
      oxidoreductases, or epimerases based on genomic context conservation. We
      demonstrate for Bacillus licheniformis and Rhodobacter sphaeroides that the
      corresponding genes are preceded by a highly conserved promoter motif and are the
      only detectable targets of ECF41-dependent gene regulation. In contrast to other
      ECF sigma factors, proteins of group ECF41 contain a large C-terminal extension,
      which is crucial for sigma factor activity. Our data demonstrate that ECF41 sigma
      factors are regulated by a novel mechanism based on the presence of a fused
      regulatory domain.

PMID- 22950026
TI  - Prokaryotic community structure and respiration during long-term incubations.
AB  - Despite the importance of incubation assays for studies in microbial ecology that
      frequently require long confinement times, few reports are available in which
      changes in the assemblage structure of aquatic prokaryotes were monitored during
      long-term incubations. We measured rates of dissolved organic carbon degradation
      and microbial respiration by consumption of dissolved oxygen (DO) in four
      experiments with Lake Kinneret near-surface water and, concomitantly, we analyzed
      the variability in prokaryotic community structure during long-term dark bottle
      incubations. During the first 24 h, there were only minor changes in bacterial
      community composition. Thereafter there were marked changes in the prokaryotic
      community structure during the incubations. In contrast, oxygen consumption rates
      (a proxy for both respiration and dissolved organic carbon degradation rates)
      remained stable for up to 10-23 days. This study is one of the first to examine
      closely the phylo-genetic changes that occur in the microbial community of
      untreated freshwater during long-term (days) incubations in dark, sealed
      containers. Novel information on the diversity of the main bacterial phylotypes
      that may be involved in dissolved organic matter degradation in lake Kinneret is
      also provided. Our results suggest that, under certain ecological settings,
      constant community metabolic rates can be maintained as a result of shifts in
      community composition.

PMID- 22950027
TI  - Identification of functions linking quorum sensing with biofilm formation in
      Burkholderia cenocepacia H111.
AB  - Burkholderia cenocepacia has emerged as an important pathogen for patients
      suffering from cystic fibrosis (CF). Previous work has shown that this organism
      employs the CepIR quorum-sensing (QS) system to control the expression of
      virulence factors as well as the formation of biofilms. To date, however, very
      little is known about the QS-regulated virulence factors and virtually nothing
      about the factors that link QS and biofilm formation. Here, we have employed a
      combined transcriptomic and proteomic approach to precisely define the QS regulon
      in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR
      activated loci, three were analyzed in better detail for their roles in biofilm
      development: (i) a gene cluster coding for the BclACB lectins, (ii) the large
      surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants
      revealed that BapA plays a major role in biofilm formation on abiotic surfaces
      while inactivation of the type I pilus showed little effect both in a static
      microtitre dish-based biofilm assay and in flow-through cells. Inactivation of
      the bclACB lectin genes resulted in biofilms containing hollow microcolonies,
      suggesting that the lectins are important for biofilm structural development.

PMID- 22950029
TI  - Atopic Sensitization is Associated With Severe Lower Respiratory Illness in
      Children With Pandemic H1N1 Influenza Viral Infection.

PMID- 22950031
TI  - The cockroach and allergic diseases.
AB  - The cockroach represents one of the most common sources of indoor allergens
      worldwide, and 40%-60% of patients with asthma in urban and inner-city areas
      possess IgE antibodies to cockroach allergens. In Korean homes, four cockroach
      species have been found, of which the most commonly encountered is the German
      cockroach. The pathogenic mechanism underlying the association between cockroach
      allergens and allergic diseases has not been fully elucidated. Allergenicity is
      associated with the cockroach allergens themselves, enzymatic protease activity,
      and ligands for pattern recognition receptors. Although allergen-specific
      adaptive immune responses orchestrate the cockroach allergic response, recent
      data suggest that the innate immune system is also a critical contributor to
      pathogenesis. We review the current evidence for the demographics of cockroach
      exposure and sensitization, characteristics of cockroach allergens, and
      inflammatory responses to cockroach allergens initiated through protease
      dependent pathways.

PMID- 22950030
TI  - Immunologic evaluation of drug allergy.
AB  - Hypersensitivity drug reactions (HDR) consist of an individual abnormal response
      with the involvement of the immunological system. In addition to specific
      immunological mechanisms where specific antibodies or sensitised T cells
      participate, release of inflammatory mediators by non-specific immunological
      recognition may also occur. Within this category are one of the most common
      groups of drugs, the non-steroidal anti-inflammatory drugs. In addition to
      chemical drugs new emerging ones with an increasing protagonism are biological
      agents like humanised antibodies and others. For IgE dependent reactions both in
      vivo and in vitro tests can be used for the immunological evaluation. Sensitivity
      of these is not optimal and very often a drug provocation test must be considered
      for knowing the mechanism involved and/or establishing the diagnosis. For non
      immediate reactions also both in vivo and in vitro tests can be used. Sensitivity
      for in vivo tests is generally low and in vitro tests may be needed for the
      immunological evaluation. Immunohistochemical studies of the affected tissue
      enable a more precise classification of non-immediate reactions. The
      monitorization of the acute response of the reactions has given clues for
      understanding these reactions and has promising results for the future of the
      immunological evaluation of HDR.

PMID- 22950032
TI  - The predictors of poorly controlled asthma in elderly.
AB  - PURPOSE: To evaluate asthma control in elderly individuals and identify the
      factors that predict poor control. METHODS: A retrospective, observational study
      evaluating 108 elderly individuals with asthma (59 females: >=60 years, mean age:
      70.5 years) was conducted at Ajou University Hospital from October 2010 to March
      2011. Subjects were classified into two groups according to scores on the asthma
      control test (ACT). Group I consisted of 38 patients with ACT scores <=19 (poor
      controllers) and group II included 70 patients with ACT scores >19 (controllers).
      Clinical data was analyzed. Spirometry was performed, and the ACT and asthma
      quality-of-life survey were completed. Medication possession ratios were
      calculated to evaluate compliance. RESULTS: Of the 108 enrolled subjects, 54.6%
      were female, 7.5% were obese, and 49.0% were atopic. The mean age of the patients
      was 70.5, and the average of time patients had suffered from asthma was 15.5
      years. Comorbid conditions were found in more than 80% of the patients. Allergic
      rhinitis was most common comorbid condition; this was followed by cardiovascular
      disease and degenerative arthritis (76.9%, 65.7%, and 51.9%, respectively). Many
      patients (35.2%) were in poorly controlled states characterized by significantly
      lower asthma quality of life scores (P<0.001) and higher admission rates
      (P=0.034). Multivariate logistic regression analysis showed that a history of
      pulmonary tuberculosis was a predictor of poorly controlled asthma in elderly
      individuals even after adjusting for age, sex, smoking, lung function and other
      comorbidities (OR=4.70, CI=1.06-20.81, P=0.042). CONCLUSIONS: The asthma of more
      than one-third of elderly individuals with this condition was poorly controlled,
      and a history of pulmonary tuberculosis may have contributed to this outcome.
      Proper evaluation and management of comorbid conditions in elderly patients with
      asthma is essential for the achievement of better control of the disease and a
      higher quality of life for those who suffer from it.

PMID- 22950033
TI  - Increased Prevalence of H1N1-Induced Severe Lower Respiratory Tract Diseases in
      Children With Atopic Sensitization.
AB  - PURPOSE: Viral infection is the most common aggravating factor for childhood
      asthma. Asthma may be a risk factor for severe respiratory symptoms in children
      with lower respiratory tract infections of viral etiology. Influenza A infection
      enhances Th2-polarization to house dust mites during the acute phase and leads to
      lung dysfunction in a mouse model. However, there are no data on the relationship
      between atopic sensitization and H1N1 (Influenza A) infection in humans. To
      investigate whether atopic sensitization is associated with the severity of H1N1
      pneumonia, we compared clinical features and the atopic sensitization rate
      between children with and without H1N1 infection. METHODS: Using reverse
      transcription-polymerase chain reactions, we investigated H1N1 virus infection in
      214 children who were hospitalized with high fever and respiratory symptoms from
      September 2009 to February 2010. We also performed immunoassays for total and
      specific IgEs to six common aeroallergens. Atopy was defined as positivity for
      more than one specific IgE. The clinical severity of pneumonia was evaluated
      based on intensive care unit admission, oxygen therapy, steroid therapy, and
      atelectasis. RESULTS: There were 70 H1N1-positive children, 42.9% of whom had
      pneumonia. Children with H1N1 infection were older and had a higher prevalence of
      atopic sensitization and pneumonia compared with H1N1-negative children. The rate
      of atelectasis was higher in children with H1N1 pneumonia than in children with
      non-H1N1 pneumonia. Among children with H1N1 viral infection, those with atopic
      sensitization had a higher prevalence of intensive care unit admission and oxygen
      therapy, and a longer duration of hospitalization than non-atopic children. There
      were no differences between atopic and non-atopic children without H1N1 viral
      infection. CONCLUSIONS: The prevalence of H1N1-induced severe lower respiratory
      tract diseases is higher in children with atopic sensitization.

PMID- 22950034
TI  - Clinical Features and the Diagnostic Value of Component Allergen-Specific IgE in
      Hymenoptera Venom Allergy.
AB  - PURPOSE: Although patient history is vital for the diagnosis of hymenoptera venom
      allergy, specific IgE detection is also important to identify the culprit insect
      and monitor the effect of immunotherapy. We evaluated the diagnostic value of
      serum-specific IgE detection of hymenoptera venom component allergens and
      documented changes in allergen-specific IgE after immunotherapy. METHODS: Fifty
      six hymenoptera venom allergy patients receiving venom immunotherapy were
      recruited from Ajou University Hospital, Korea. The clinical manifestations of
      the patients were noted, and serum-specific IgE detection was performed, using
      conventional venom extracts as well as component allergens. Data were analyzed
      retrospectively. RESULTS: A total of 35 (62.5%) patients were male, and 33
      (73.3%) patients were atopic. The mean patient age was 44.9+/-13.8 years.
      Localized reactions occurred in 23.2% of patients, and systemic reactions
      occurred in 76.8%. The most common clinical manifestations included skin
      involvement, such as urticaria and angioedema, and respiratory involvement.
      Yellow jackets were the most frequent culprit insect, followed by yellow hornets,
      white-faced hornets, honeybees, and paper wasps, as determined at the time of
      diagnosis. Double sensitization to both Apidae and Vespidae species was detected
      in 70.9% of patients. The positive predictive values (PPV) of rVes v 5-specific
      and rPol d 5-specific IgE detection were 85.7% and 87.5%, respectively, which
      correlated well with conventional venom extract-specific IgE detection (r=0.762
      and r=0.757, respectively). In contrast, the PPV of rApi m 1-specific IgE
      detection at the time of diagnosis was 34.8%. Three years of venom immunotherapy
      resulted in decreased venom-specific IgE, particularly IgE specific for Vespidae
      venom components. CONCLUSIONS: Stings by yellow jackets and male sex may be risk
      factors for hymenoptera venom allergy in Korea. Vespidae component-specific IgE,
      but not Apidae component-specific IgE, had diagnostic and monitoring value in
      hymenoptera venom allergy comparable to that of conventional hymenoptera venom
      extract-specific IgE.

PMID- 22950035
TI  - Evaluation of atorvastatin for the treatment of patients with asthma: a double
      blind randomized clinical trial.
AB  - PURPOSE: Statins are known as cholesterol-lowering agents, but have been
      suggested for the treatment of asthma because of their anti-inflammatory effects.
      In this study, the potential therapeutic effects of atorvastatin were
      investigated in asthmatic patients. METHODS: A total of 62 patients with
      persistent mild to moderate asthma who presented at asthma clinics of Arak
      University of Medical Sciences were recruited in a double-blind randomized
      clinical trial. The asthma clinical control score was assessed based on the
      standardized Asthma Control Test. Lung volume, i.e., percentage of forced
      expiratory volume in one second (FEV1%) and percentage of forced vital capacity
      (FVC%), and peripheral blood eosinophils were also measured. The intervention
      group was treated with atorvastatin 40 mg per day for 8 weeks, while the control
      group received a placebo. Asthma controller treatments were not changed. At the
      beginning and end of the study, serum cholesterol and triglyceride levels were
      measured to evaluate adherence of the patients to the treatment. RESULTS: The
      asthma control score did not significantly differ between the intervention and
      control groups (P=0.06). Difference in FEV1%, FVC%, and blood eosinophil count
      between the intervention and control groups were not statistically significant
      (P>0.05). The differences in post-treatment cholesterol and low-density
      lipoprotein cholesterol levels were significant (P<0.05). CONCLUSIONS: Our study
      shows that atorvastatin is not effective in the treatment of persistent mild to
      moderate asthma.

PMID- 22950036
TI  - TLR4, 5, and 9 Agonists Inhibit Murine Airway Invariant Natural Killer T Cells in
      an IL-12-Dependent Manner.
AB  - PURPOSE: Invariant natural killer T (iNKT) cells may play an important role in
      the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the
      function of iNKT cells may have therapeutic potential to control asthma. We
      hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes
      in the cytokine milieu may modify and even inhibit the function of airway iNKT
      cells in asthma. METHODS: Because increased alpha-galactosylceramide (GalCer)
      induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells,
      alpha-GalCer-induced AHR, as well as inflammatory cells and cytokines in
      bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo
      treatment with LPS, flagellin, or CpG in naive BALB/c mice. Intracellular IL-4
      and IFN-gamma were measured in spleen iNKT cells after in vitro treatment with
      LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined.
      RESULTS: Intranasal administration of LPS, flagellin, or CpG reduced development
      of alpha-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2
      cytokine responses in BAL fluid, while producing IL-12 in BAL fluid.
      Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of
      LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced
      production of IL-4 and IFN-gamma from alpha-GalCer-stimulated spleen iNKT cells;
      these effects were ameliorated by addition of anti-IL-12 mAb. CONCLUSIONS: TLR4,
      5, and 9 agonists may suppress the function of airway and spleen iNKT cells via
      IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in
      suppression by these TLR agonists.

PMID- 22950037
TI  - Clinical features of allergic bronchopulmonary aspergillosis in Korea.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a complex disease, triggered by
      a hypersensitivity reaction to the allergen Aspergillus fumigatus. This disease
      occurs frequently in patients with cystic fibrosis and severe asthma in Western
      countries, with a prevalence of 2%-15%. However, there have been only a few case
      reports in Korea. We investigated the clinical and immunological features of
      patients with ABPA. Ten adult patients diagnosed with ABPA, according to
      Greenberger's criteria, were analyzed during the period January 2001 to December
      2010 in a tertiary hospital. Skin-prick tests, pulmonary function tests, and high
      resolution computed tomography (HRCT) were performed, and total serum IgE and A.
      fumigatus-specific IgE were measured. The patient cohort consisted of men who
      were middle-aged (median, 62.5; range, 19.0-79.0 years) at the diagnosis of ABPA
      with a long duration of asthma (median, 15.0; range, 1-48 years). Approximately
      40% of the patients had a history of pulmonary tuberculosis more than 10 years
      prior to the study (median 23.5; range, 10.0-31.0 years) accompanied by severe
      obstructive lung function and radiological post-tuberculous destructive lung
      lesions. These patients also tended to have increased levels of immunologic
      parameters, such as total eosinophil count, total IgE, and A. fumigates-specific
      IgE, compared to those without tuberculosis sequels. Two patients with steroid
      dependent asthma were treated with anti-IgE therapy and showed good responses. We
      report the clinical features of 10 ABPA patients, including 4 with histories of
      post-tuberculosis destructive lesions. Furthermore, anti-IgE antibody therapy may
      be an alternative strategy in cases of steroid-dependent ABPA.

PMID- 22950038
TI  - A case of allopurinol-induced fixed drug eruption confirmed with a lymphocyte
      transformation test.
AB  - Allopurinol is one of the causative drugs that induce fixed drug eruption (FDE).
      The lymphocyte transformation test (LTT) is a safe and reliable diagnostic
      procedure for drug allergy, but is reported to be rarely positive in patients
      with FDE. In the current case, we performed an LTT and successfully confirmed
      allopurinol as the offending drug. This case report suggests that an LTT should
      be an optional diagnostic tool for FDE or delayed reaction due to allopurinol.

PMID- 22950039
TI  - Mood symptoms contribute to working memory decrement in active-duty soldiers
      being treated for posttraumatic stress disorder.
AB  - A significant proportion of military veterans of operations in Afghanistan and
      Iraq have been diagnosed with posttraumatic stress disorder (PTSD). Growing
      evidence suggests that neuropsychological deficits are a symptom of PTSD. The
      current study investigated neurocognitive functioning among soldiers diagnosed
      with PTSD. Specifically, active-duty soldiers with and without a diagnosis of
      PTSD were assessed for performance on tests of attention and working memory. In
      addition, factors such as combat experience, depression, anxiety, PTSD symptom
      severity, and alcohol consumption were explored as possible mediators of group
      differences in neurocognitive functioning. Twenty-three active-duty soldiers
      diagnosed with PTSD were matched with 23 healthy Soldier controls; all were
      administered the Attention Network Task (ANT), Backward Digit Span (BDS) task,
      Beck Depression Inventory, Beck Anxiety Inventory, PTSD Checklist-Military
      Version, Combat Exposure Scale, and Modified Drinking Behavior Questionnaire.
      Soldiers diagnosed with PTSD performed significantly worse on the working memory
      task (BDS) than healthy controls, and reported greater levels of PTSD symptoms,
      combat exposure, depression, and anxiety. However, after controlling for
      depression and anxiety symptoms, the relationship between PTSD and working memory
      was no longer present. The results indicate that PTSD is accompanied by deficits
      in working memory, which appear to be partially attributed to anxiety and
      depression symptoms.

PMID- 22950040
TI  - Hypothalamic expression of Peg3 gene is associated with maternal care differences
      between SM/J and LG/J mouse strains.
AB  - Maternal care is essential in mammals, and variations in the environment provided
      by mothers may directly influence the viability of newborns and emotional
      behavior later in life. A previous study investigated genetic variations
      associated with maternal care in an intercross of LG/J and SM/J inbred mouse
      strains and identified two single-locus QTLs (quantitative trait loci). Here, we
      selected three candidate genes located within these QTLs intervals; Oxt on
      chromosome 2, and FosB and Peg3 on chromosome 7 and tested their association with
      maternal care. LG/J females showed impaired postpartum nest building and pup
      retrieval, a one-day delay in milk ejection, reduced exploratory activity, and
      higher anxiety-like behavior when compared to SM/J females. The nucleotide
      sequences of Oxt and FosB were similar between strains, as were their
      hypothalamic expression levels. Conversely, Peg3 nucleotide sequences showed four
      nonsynonymous replacement substitutions on LG/J dams, T11062G, G13744A, A13808G,
      and G13813A, and a 30 base pair (10 aa) in tandem repeat in the coding region
      with three copies in SM/J and five copies in LG/J. Maternal care impaired LG/J
      mothers express 37% lower Peg3 mRNA levels in the hypothalamus on the second
      postpartum day. We also found an association of the Peg3 repeat-variant and poor
      maternal care in F(2) heterozygote females derived from a LG/J * SM/J intercross.
      These results may suggest that the maternally imprinted Peg3 gene is responsible
      for the single-locus QTL on chromosome 7 that has been shown to influence
      maternal care in these strains. Furthermore, these data provide additional
      support for an epigenetic regulation of maternal behavior.

PMID- 22950041
TI  - Use of cranial CT to identify a new infarct in patients with a transient ischemic
      attack.
AB  - Research on infarct detection by noncontrast cranial computed tomography (CCT) in
      patients with transient ischemic attack (TIA) is sparse. However, the aims of
      this study are to determine the frequency of new infarcts in patients with TIA,
      to evaluate the independent predictors of infarct detection, and to investigate
      the association between a new infarct and early short-term risk of stroke during
      hospitalization. We prospectively evaluated 1533 consecutive patients (mean age,
      75.3 +/- 11 years; 54% female; mean National Institutes of Health Stroke Scale
      [NIHSS] score, 1.7 +/- 2.9) with TIA who were admitted to hospital within 48 h of
      symptom onset. A new infarct was detected by CCT in 47 (3.1%) of the 1533
      patients. During hospitalization, 17 patients suffered a stroke. Multivariate
      logistic regression analysis revealed the following independent predictors for
      infarct detection: NIHSS score >=10 (odds ratio [OR], 4.8), time to CCT
      assessment >6 h (OR 2.2), and diabetes (OR 2.3). The evidence of a new infarct
      was not associated with the risk of stroke after TIA. The frequency of a new
      infarct in patients with TIA using CCT is low. The use of the CCT tool to predict
      the stroke risk during hospitalization in patients with TIA is found to be
      inappropriate. The estimated clinical predictors are easy to use and may help
      clinicians in the TIA work up.

PMID- 22950042
TI  - The relationship between nerve conduction velocity and fiber morphology during
      peripheral nerve regeneration.
AB  - We analyzed the relationship between motor nerve conduction velocity (MCV) and
      morphological changes in regenerating nerve fibers at different times after
      sciatic nerve transection to identify reliable indices of functional recovery.
      Thirty rats were divided into five equal groups, one control group and four
      groups subjected to sciatic nerve transection and immediate suturing, followed by
      regeneration for 50, 100, 150, and 200 days, respectively. MCV was measured in
      each group, followed by morphometric analyses of fibers of the common peroneal
      nerve. MCV increased progressively with time after nerve transection, although it
      remained lower than the control velocity. Mean fiber diameter (axon plus myelin
      sheath) also increased with time after nerve transection. Recovery of mean fiber
      diameter was well correlated with MCV, even though regenerating nerves likely
      contained many small nonconducting fibers. In contrast, the change in the mean
      diameter of regenerating axons and relative myelin thickness (g-ratio) did not
      provide an accurate measure of recovery as they were not increasing in a time
      dependent manner. Furthermore, internodal length changed only slightly with
      increasing fiber diameter in regenerating nerves; therefore, the regression
      relation between fiber diameter and internodal length was not a sensitive index
      of recovery. MCV and mean fiber diameter were the most sensitive indices of
      functional recovery during sciatic nerve regeneration.

PMID- 22950043
TI  - Pharmacological evidence that D-aspartate activates a current distinct from
      ionotropic glutamate receptor currents in Aplysia californica.
AB  - D-Aspartate (D-Asp) activates a nonspecific cation current of unknown identity
      independent of L-glutamate (L-Glu) in neurons of Aplysia californica. Whole-cell
      voltage clamp studies were conducted using primary cultures of Aplysia buccal S
      cluster (BSC) neurons to characterize these receptor channels pharmacologically.
      The N-methyl-D-aspartate receptor (NMDAR) coagonist glycine potentiated D-Asp
      currents only at -30 mV, while D-serine did not potentiate D-Asp currents at any
      amplitude. Portions of D-Asp currents were blocked by the L-Glu antagonists
      kynurenate, DL-2-amino-5-phosphonopentanoic acid (APV), (2S,3R)-1-(phenanthren-2
      carbonyl)piperazine-2,3-dicarboxylic acid (PPDA), and 1,3-dihydro-5-[3-[4
      (phenylmethyl)-1-2H-benzimidazol-2-one (TCS46b), suggesting that L-Glu channels,
      particularly NMDAR-like channels, may partially contribute to D-Asp whole-cell
      currents. In contrast, L-Glu currents were unaffected by APV, and showed greater
      block by kynurenate, suggesting that D-Asp and L-Glu act, in part, at different
      sites. The excitatory amino acid transport blocker DL-threo-b-Benzyloxyaspartic
      acid (TBOA) blocked a fraction of D-Asp currents, suggesting that currents
      associated with these transporters also contribute. Non-NMDA L-GluR antagonists
      that preferentially block alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic
      acid (AMPA)/kainate receptors significantly increased D-Asp currents, suggesting
      a possible allosteric potentiating effect of these antagonists on D-Asp
      receptors. L-Glu-induced currents were significantly reduced in the presence of
      bath-applied D-Asp, whereas bath-applied L-Glu had no effect on D-Asp-induced
      currents. The mixed effects of these agents on D-Asp-induced currents in Aplysia
      illustrate that the underlying channels are not uniformly characteristic of any
      known agonist associated channel type.

PMID- 22950044
TI  - The spatiotemporal localization of JAM-C following sciatic nerve crush in adult
      rats.
AB  - JAM-C is a junctional adhesion molecule, enriched at tight junctions on
      endothelial and epithelial cells, and also localized to Schwann cells at
      junctions between adjoining myelin end loops. The role of JAM-C following
      peripheral nerve injury (PNI) is currently unknown. We examined the localization
      of JAM-C after sciatic nerve crush injury in adult rats. JAM-C immunoreactivity
      was present in paranodes and incisures in sham surgery control nerve, but distal
      to the crush injury significantly decreased at three and 14 days. JAM-C was re
      expressed at 28 days and, by 56 days, was significantly increased in the distal
      nerve compared to controls. In a 7-mm length of sciatic nerve sampled distal to
      the crush site, the densities of JAM-C immunoreactive paranodes increased in the
      distal direction. Conversely, the densities of JAM-C immunoreactive incisures
      were highest immediately distal to the crush site and decreased in the more
      distal direction. Further analysis revealed a strong correlation between JAM-C
      localization and remyelination. Fifty-six days after crush injury, greater
      densities of JAM-C paranodes were seen compared to the nodal marker jacalin,
      suggesting that paranodal JAM-C precedes node formation. Our data are the first
      to demonstrate a potential role of JAM-C in remyelination after PNI.

PMID- 22950045
TI  - Impaired social decision making in patients with major depressive disorder.
AB  - Research on how depression influences social decision making has been scarce.
      This study investigated how people with depression make decisions in an
      interpersonal trust-reciprocity game. Fifty female patients diagnosed with major
      depressive disorders (MDDs) and 49 healthy women participated in this study. The
      experiment was conducted on a one-to-one basis. Participants were asked to play
      the role of a trustee responsible for investing money given to them by an
      anonymous female investor playing on another computer station. In each trial, the
      investor would send to a participant (the trustee) a request for a certain
      percentage of the appreciated investment (repayment proportion). Since only the
      participant knew the exact amount of the appreciated investment, she could decide
      to pay more (altruistic act), the same, or less (deceptive act) than the
      requested amount. The participant's money acquired in the trial would be
      confiscated if her deceptive act was caught. The frequency of deceptive or
      altruistic decisions and relative monetary gain in each decision choice were
      examined. People with depression made fewer deceptive and fewer altruistic
      responses than healthy controls in all conditions. Moreover, the specific
      behavioral pattern presented by people with depression was modulated by the task
      factors, including the risk of deception detection and others' intentions
      (benevolence vs. malevolence). Findings of this study contribute to furthering
      our understanding of the specific pattern of social behavioral changes associated
      with depression.

PMID- 22950046
TI  - A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in
      neurodevelopment and disease.
AB  - Reactive oxygen species (ROS) play essential roles in cell signaling, survival,
      and homeostasis. Aberrant ROS lead to disease and contribute to the aging
      process. Numerous enzymes and vigilant antioxidant pathways are required to
      regulate ROS for normal cellular health. Mitochondria are a major source of ROS,
      and mechanisms to prevent elevated ROS during oxidative phosphorylation require
      super oxide dismutase (SOD) activity. SOD2, also known as MnSOD, is targeted to
      mitochondria and is instrumental in regulating ROS by conversion of superoxides
      to hydrogen peroxide, which is further broken down into H(2)O and oxygen. Here,
      we describe the identification of a novel mutation within the mitochondrial SOD2
      enzyme in Drosophila that results in adults with an extremely shortened life
      span, sensitivity to hyperoxia, and neuropathology. Additional studies
      demonstrate that this novel mutant, SOD2(bewildered), exhibits abnormal brain
      morphology, suggesting a critical role for this protein in neurodevelopment. We
      investigated the basis of this neurodevelopmental defect and discovered an
      increase in aberrant axonal that could underlie the aberrant neurodevelopment and
      brain morphology defects. This novel allele, SOD2(bewildered), provides a unique
      opportunity to study the effects of increased mitochondrial ROS on neural
      development, axonal targeting, and neural cell degeneration in vivo.

PMID- 22950047
TI  - Prevalence, laterality, and comorbidity of hippocampal sclerosis in an autopsy
      sample.
AB  - Hippocampal sclerosis (HS) is a common and often asymmetric neuropathological
      finding among elderly persons who experience progressive memory loss, but its
      cause is unknown and it is rarely diagnosed during life. In order to improve both
      understanding and diagnosis of late-life HS, bilateral hippocampi and cerebral
      hemispheres were reviewed in 130 consecutive autopsy cases drawn from a
      longitudinal study of subjects with subcortical ischemic vascular dementia (IVD),
      Alzheimer disease (AD) and normal aging. HS was found in 31 of 130 cases (24.5%).
      Of these, 45% were bilateral, 32% left-sided, and 23% right-sided. The majority
      of HS cases involved the entire rostral-caudal extent of the hippocampus.
      However, in 7 cases HS was focal in nature and was only found at or anterior to
      the lateral geniculate nucleus. In 77% of cases, HS was accompanied by other
      types of pathology ('mixed' HS), but in 23% of cases it was the sole
      neuropathologic finding ('pure' HS). TDP-43-positive cytoplasmic inclusions were
      found in dentate granule cells in 93% of all HS cases, 55% of AD cases with no
      HS, but 0% of IVD cases with no HS. MRI hippocampal volumes were significantly
      lower in bilateral HS compared to AD (p < 0.001) and in unilateral HS cases
      compared to cases with intact hippocampi (p < 0.001). Since HS may occur
      unilaterally in approximately a quarter of cases, its prevalence may be
      underestimated if only one cerebral hemisphere is examined. The presence of TDP
      43 inclusions in HS cases, regardless of accompanying pathologies (e.g., AD, IVD,
      FTLD), is consistent with an underlying neurodegenerative pathogenetic mechanism.
      Further studies are warranted to determine whether greater severity of
      hippocampal atrophy on MRI may assist the clinical differentiation of HS from AD.

PMID- 22950048
TI  - A promising randomized trial of a new therapy for obsessive-compulsive disorder.
AB  - Pharmacotherapy and cognitive-behavioral therapy (CBT) are currently the most
      effective interventions for treating obsessive-compulsive disorder (OCD). These
      treatments, however, are time consuming and in some cases the patients do not
      show significant improvement. In all, 30%-60% of OCD patients do not respond
      adequately to pharmacotherapy and 20%-40% of OCD patients who complete CBT do not
      improve significantly, suggesting a more efficacious approach is needed. The
      objectives of this study are to demonstrate an efficacious pharmacotherapy plus
      psychotherapy, named cognitive-coping therapy (CCT), for OCD and to investigate
      the efficacy of this approach in a larger sample size. Therefore, a total of 108
      patients with OCD were randomly allocated into three groups: pharmacotherapy (N =
      38), pharmacotherapy plus CBT (PCBT, N = 34), and pharmacotherapy plus CCT (PCCT,
      N = 36). The severity of symptoms and the patients' functioning were assessed
      pretreatment and after 7, 14, 21 days, and 1-, 3-, 6-, and 12-month treatment
      using the Yale-Brown Obsessive Compulsive Scale and Global Assessment of
      Functioning (GAF). Compared with the pharmacotherapy and PCBT groups, the
      severity of OCD symptoms was significantly reduced (P < 0.001), the rates of
      response (100%) and remission (85.0%) were significantly higher (P < 0.001), and
      relapse rate was lower (P = 0.017) in PCCT group during the 1-year follow-up. In
      addition, the GAF score was significantly higher in the PCCT group than in the
      other two groups (P < 0.001). Our preliminary data suggest that PCCT is a more
      efficacious psychotherapy for OCD patients than pharmacotherapy or PCBT.

PMID- 22950049
TI  - Maternal separation is associated with strain-specific responses to stress and
      epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse.
AB  - Stressful events early in life have been widely linked to behavioral phenotypes
      and have been implicated in the development of psychiatric disorders. Using a
      maternal separation paradigm, we investigated phenotypic and epigenetic changes
      following early life stress in two inbred strains of mice, C57BL/6J and DBA/2J.
      We found an increase in the corticosterone response to stress in male, C57BL/6J
      mice that had undergone maternal separation compared to controls. In addition,
      early life stress induced a number of mild but significant behavioral changes,
      many of which were sex and strain dependent. Following maternal separation
      anxiety was decreased in males but increased in DBA/2J females, DBA/2J males
      displayed reduced exploration of a novel object, and baseline activity was
      altered in males of both strains. Finally, we examined DNA methylation levels in
      the hippocampus across promoter regions of Nr3c1, Avp, and Nr4a1, and found
      altered levels at several CpG sites in maternally separated male mice compared to
      controls. This study contributes to a growing body of recent literature
      suggesting that epigenetic changes may mediate the impact of early life stress on
      behavior. In particular, we establish that the phenotypic and epigenetic
      responses to an adverse environment differ as a function of genetic background.

PMID- 22950050
TI  - Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural
      properties, regulation, and physiological role in protection against oxidative
      stress and mitochondrial dysfunction.
AB  - Uncoupling proteins (UCPs) belong to a large family of mitochondrial solute
      carriers 25 (SLC25s) localized at the inner mitochondrial membrane. UCPs
      transport protons directly from the intermembrane space to the matrix. Of five
      structural homologues (UCP1 to 5), UCP4 and 5 are principally expressed in the
      central nervous system (CNS). Neurons derived their energy in the form of ATP
      that is generated through oxidative phosphorylation carried out by five
      multiprotein complexes (Complexes I-V) embedded in the inner mitochondrial
      membrane. In oxidative phosphorylation, the flow of electrons generated by the
      oxidation of substrates through the electron transport chain to molecular oxygen
      at Complex IV leads to the transport of protons from the matrix to the
      intermembrane space by Complex I, III, and IV. This movement of protons to the
      intermembrane space generates a proton gradient (mitochondrial membrane
      potential; MMP) across the inner membrane. Complex V (ATP synthase) uses this MMP
      to drive the conversion of ADP to ATP. Some electrons escape to oxygen-forming
      harmful reactive oxygen species (ROS). Proton leakage back to the matrix which
      bypasses Complex V resulting in a major reduction in ROS formation while having a
      minimal effect on MMP and hence, ATP synthesis; a process termed "mild
      uncoupling." UCPs act to promote this proton leakage as means to prevent
      excessive build up of MMP and ROS formation. In this review, we discuss the
      structure and function of mitochondrial UCPs 4 and 5 and factors influencing
      their expression. Hypotheses concerning the evolution of the two proteins are
      examined. The protective mechanisms of the two proteins against neurotoxins and
      their possible role in regulating intracellular calcium movement, particularly
      with regard to the pathogenesis of Parkinson's disease are discussed.

PMID- 22950051
TI  - The use of P300-based BCIs in amyotrophic lateral sclerosis: from augmentative
      and alternative communication to cognitive assessment.
AB  - The use of augmentative and alternative communication (AAC) tools in patients
      with amyotrophic lateral sclerosis (ALS), as effective means to compensate for
      the progressive loss of verbal and gestural communication, has been deeply
      investigated in the recent literature. The development of advanced AAC systems,
      such as eye-tracking (ET) and brain-computer interface (BCI) devices, allowed to
      bypass the important motor difficulties present in ALS patients. In particular,
      BCIs could be used in moderate to severe stages of the disease, since they do not
      require preserved ocular-motor ability, which is necessary for ET applications.
      Furthermore, some studies have proved the reliability of BCIs, regardless of the
      severity of the disease and the level of physical decline. However, the use of
      BCI in ALS patients still shows some limitations, related to both technical and
      neuropsychological issues. In particular, a range of cognitive deficits in most
      ALS patients have been observed. At the moment, no effective verbal-motor free
      measures are available for the evaluation of ALS patients' cognitive integrity;
      BCIs could offer a new possibility to administer cognitive tasks without the need
      of verbal or motor responses, as highlighted by preliminary studies in this
      field. In this review, we outline the essential features of BCIs systems,
      considering advantages and challenges of these tools with regard to ALS patients
      and the main applications developed in this field. We then outline the main
      findings with regard to cognitive deficits observed in ALS and some preliminary
      attempts to evaluate them by means of BCIs. The definition of specific cognitive
      profiles could help to draw flexible approaches tailored on patients' needs. It
      could improve BCIs efficacy and reduce patients' efforts. Finally, we handle the
      open question, represented by the use of BCIs with totally locked in patients,
      who seem unable to reliably learn to use such tool.

PMID- 22950054
TI  - The role of oxidative stress in the pathogenesis of diabetic vascular
      complications.
AB  - Oxidative stress has been paid increasing attention to as an important causative
      factor for diabetic vascular complications. Among possible various sources,
      accumulating evidence has indicated that NAD(P)H oxidase may be the most
      important source for reactive oxygen species production in diabetic vascular
      tissues. The mechanisms underlying activation and up-regulation of NAD(P)H
      oxidase has been supposed to be mediated by high glucose-induced protein kinase C
      (PKC) activation. In this review article, activation of local renin-angiotensin
      II system induced by chymase activation is also shown to amplify such a PKC
      dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the
      beneficial effect of antioxidants on diabetic vascular complications. Bilirubin
      has been recognized as a strong endogenous antioxidant. Here markedly lower
      prevalence of vascular complications is shown in diabetic patients with Gilbert
      syndrome, a congenital hyperbilirubinemia, as well as reduced markers of
      oxidative stress and inflammation. Lastly, statin, angiotensin II receptor
      blocker, chymase inhibitor, bilirubin and biliverdin, PKC beta isoform inhibitor,
      and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have
      some beneficial effect on diabetic vascular complications, via inhibiting PKC
      NAD(P)H oxidase activation, supporting the notion that this mechanism may be an
      effective therapeutic target for preventing diabetic vascular complications.

PMID- 22950055
TI  - GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases,
      is caused by the disruption of hepatic lipid homeostasis. It is associated with
      insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1
      (GLP-1) is an incretin that increases insulin sensitivity and aids glucose
      metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel
      therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing
      lipogenesis, and improving hepatic glucose metabolism. In this report, we provide
      an overview of the role and mechanism of GLP-1 in relieving NAFLD.

PMID- 22950052
TI  - Substrates of neuropsychological functioning in stimulant dependence: a review of
      functional neuroimaging research.
AB  - Stimulant dependence is associated with neuropsychological impairments. Here, we
      summarize and integrate the existing neuroimaging literature on the neural
      substrates of neuropsychological (dys)function in stimulant dependence, including
      cocaine, (meth-)amphetamine, ecstasy and nicotine dependence, and excessive
      caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls
      (HCs). Despite some inconsistencies, most studies indicated altered brain
      activation in prefrontal cortex (PFC) and insula in response to reward and
      punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation
      during craving and attentional bias paradigms in SAs compared with HCs.
      Impulsivity in SAs was associated with lower ACC and presupplementary motor area
      activity compared with HCs, and related to both ventral (amygdala, ventrolateral
      PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex)
      systems. Decision making in SAs was associated with low dorsolateral PFC activity
      and high orbitofrontal activity. Finally, executive function in SAs was
      associated with lower activation in frontotemporal regions and higher activation
      in premotor cortex compared with HCs. It is concluded that the lower activations
      compared with HCs are likely to reflect the neural substrate of impaired
      neurocognitive functions, whereas higher activations in SAs compared with HCs are
      likely to reflect compensatory cognitive control mechanisms to keep behavioral
      task performance to a similar level as in HCs. However, before final conclusions
      can be drawn, additional research is needed using neuroimaging in SAs and HCs
      using larger and more homogeneous samples as well as more comparable task
      paradigms, study designs, and statistical analyses.

PMID- 22950056
TI  - Obstructive sleep apnea and abnormal glucose metabolism.
AB  - Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially
      in subjects with obesity or diabetes. OSA is related to several metabolic
      abnormalities, including diabetes, insulin resistance, hypertension, and
      cardiovascular diseases. Although Koreans are less obese than Caucasians, the
      prevalence of OSA is comparable in both groups. Thus, the impact of OSA on
      metabolism may be similar. Many epidemiologic and experimental studies have
      demonstrated that OSA is associated with glucose intolerance and insulin
      resistance via intermittent hypoxia, sleep fragmentation, and sleep deprivation.
      The effect of continuous positive airway pressure treatment on glucose metabolism
      is still controversial. Randomized controlled trials are needed to evaluate the
      ability of OSA treatment to reduce the risk of diabetes and insulin resistance in
      subjects without diabetes and to ameliorate glucose control in patients with
      diabetes.

PMID- 22950057
TI  - Severe hypoglycemia in patients with diabetes.

PMID- 22950058
TI  - Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell
      ABCA1.
AB  - BACKGROUND: The aim of this study was to investigate the effects of balsamic
      vinegar on beta-cell dysfunction. METHODS: In this study, 28-week-old Otsuka Long
      Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet
      (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks.
      Oral glucose tolerance tests and histopathological analyses were performed
      thereafter. RESULTS: In rats fed both the both chow diet and the HFD, the rats
      given balsamic vinegar showed increased insulin staining in islets compared with
      tap water administered rats. Balsamic vinegar administration also increased beta
      cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in
      islets and decreased cholesterol levels. CONCLUSION: These findings provide the
      first evidence for an anti-diabetic effect of balsamic vinegar through
      improvement of beta-cell function via increasing beta-cell ABCA1 expression.

PMID- 22950059
TI  - Severe hypoglycemia is a serious complication and becoming an economic burden in
      diabetes.
AB  - BACKGROUND: The prevalence of hypoglycemia is increasing due to the growing
      incidence of diabetes and the latest strict guidelines for glycated hemoglobin
      (HbA1c) levels under 7%. This study examined the clinical characteristics, causal
      factors, and medical costs of severely hypoglycemic patients in an emergency room
      (ER) of Uijeongbu St. Mary's Hospital. METHODS: The study consisted of a
      retrospective analysis of the characteristics, risk factors, and medical costs of
      320 severely hypoglycemic patients with diabetes who presented to an ER of
      Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009. RESULTS:
      Most hypoglycemic patients (87.5%, 280/320) were over 60 years old with a mean
      age of 69.5+/-10.9 years and a mean HbA1c level of 6.95+/-1.46%. Mean serum
      glucose as noted in the ER was 37.9+/-34.5 mg/dL. Renal function was decreased,
      serum creatinine was 2.0+/-2.1 mg/dL and estimated glomerular filtration rate
      (eGFR) was 48.0+/-33.6 mL/min/1.73 m(2). In addition, hypoglycemic patients
      typically were taking sulfonylureas or insulin and a variety of other
      medications, and had a long history of diabetes. CONCLUSION: Severe hypoglycemia
      is frequent in older diabetic patients, subjects with low HbA1c levels, and
      nephropathic patients. Therefore, personalized attention is warranted, especially
      in long-term diabetics with multiple comorbidities who may not have been properly
      educated or may need re-education for hypoglycemia.

PMID- 22950061
TI  - Intracerebroventricular injection of metformin induces anorexia in rats.
AB  - BACKGROUND: Metformin, an oral biguanide insulin-sensitizing agent, is well known
      to decrease appetite. Although there is evidence that metformin could affect the
      brain directly, the exact mechanism is not yet known. METHODS: To evaluate
      whether metformin induces anorexia via the hypothalamus, various concentrations
      of metformin were injected into the lateral ventricle of rats through a
      chronically implanted catheter and food intake was measured for 24 hours. The
      hypothalamic neuropeptides associated with regulation of food intake were also
      analyzed following 1 hour of intracerebroventricular (ICV) injections of
      metformin. RESULTS: An ICV injection of metformin decreased food intake in a dose
      dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP
      activated protein kinase (pAMPK) increased by 3 ug with metformin treatment, but
      there was no further increase in pAMPK with increases in metformin dosage. The
      hypothalamic phosphorylated signal transducer and activator of transcription 3
      (pSTAT3) increased by 3 ug with metformin treatment, but, there was no further
      increase in pSTAT3 level following increases of metformin dosage. Hypothalamic
      proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y
      was not significantly changed. CONCLUSION: Our results suggest that metformin
      induces anorexia via direct action in the hypothalamus and the increase in
      pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK
      appears not to contribute to metformin-induced appetite reduction in normal rats.
      Further studies exploring new pathways connecting metformin and feeding
      regulation are needed.

PMID- 22950060
TI  - Influence of visceral adiposity on cardiovascular autonomic neuropathy in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to investigate the influences of visceral
      adiposity on cardiovascular autonomic neuropathy (CAN) in patients with type 2
      diabetes mellitus. METHODS: Two hundred eleven patients with type 2 diabetes
      participated in this study. Anthropometric and metabolic parameters were
      measured, and the visceral fat area was assessed using computed tomography. CAN
      was diagnosed using a cardiovascular reflex test. We analyzed the correlation
      between the visceral fat area and each parameter in this test. RESULTS: The mean
      age, body mass index (BMI), and duration of diabetes of the study population were
      60+/-14 years (mean+/-standard deviation), 25.1+/-4.2 kg/m(2), and 12.3+/-8.9
      years, respectively. The visceral fat area showed positive correlations with age,
      BMI, waist circumference, and subcutaneous fat area. There was no statistically
      significant difference in the cardiovascular reflex test outcome between genders.
      Univariate linear regression analysis showed that an increased visceral fat area
      diminished good heart rate response to a Valsalva maneuver (R(2)=4.9%, P=0.013 in
      an unadjusted model), but only in women. This statistical association was
      preserved after adjusting for age and BMI (R(2)=9.8%, P=0.0072). CONCLUSION: The
      results of this study suggest that visceral adiposity contributes to an autonomic
      imbalance to some degree, as demonstrated by the impaired cardiovascular reflex
      test among women with type 2 diabetes.

PMID- 22950062
TI  - Total energy intake may be more associated with glycemic control compared to each
      proportion of macronutrients in the korean diabetic population.
AB  - BACKGROUND: Major macronutrients for energy intake vary among countries and
      cultures. Carbohydrates, including rice, are the major component of daily energy
      intake in Korea. The aim of this study was to examine the association of daily
      energy intake or each proportion of macronutrients, especially carbohydrates,
      with glycemic control in diabetic Koreans. METHODS: A total of 334 individuals
      with diabetes (175 men, age 57.4+/-0.8 years; 159 women, age 60.9+/-0.9 years)
      who participated in the 2005 Korean National Health and Nutrition Examination
      Survey were examined. Glycemic control was categorized based on concentration of
      glycated hemoglobin (HbA1c; HbA1c <=6.5%; 6.6% to 8.0%; >=8.1%). Dietary intake
      was assessed by using a 24-recall item questionnaire. RESULTS: High total energy
      intake was associated with poor glycemic control (HbA1c <=6.5%, 1,824+/-75 kcal;
      6.6% to 8.0%, 1,990+/-57 kcal; >=8.1%, 2,144+/-73 kcal; P value for trend=0.002).
      Each proportion of protein, fat, or carbohydrate was not associated with glycemic
      control. Even after adjusting for several parameters, the association of daily
      energy intake with glycemic control still persisted. CONCLUSION: Total energy
      intake may be more closely related to glycemic control than each proportionof
      macronutrients in Korean diabetics.

PMID- 22950063
TI  - Urinary neutrophil gelatinase-associated lipocalin levels in comparison with
      glomerular filtration rate for evaluation of renal function in patients with
      diabetic chronic kidney disease.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising
      biomarker of acute kidney injury. There is a growing body of evidence suggesting
      that NGAL is also a marker of kidney disease and severity in chronic kidney
      disease (CKD). We studied the utility of urinary NGAL in more accurately
      predicting renal function in patients with diabetic CKD. METHODS: We studied
      possible relationships between urinary NGAL, estimated glomerular filtration rate
      (eGFR), and proteinuria in diabetic CKD patients and in healthy populations.
      RESULTS: Urinary NGAL levels were significantly higher in CKD patients than in
      healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL,
      P=0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3]
      mL/min/1.73 m(2) vs. 85.6 [72 to 106.7] mL/min/1.73 m(2), P<0.0001). The urinary
      NGAL level showed a significant inverse correlation with GFR (r=-0.5634,
      P<0.0001). The correlation analyses between urinary protein level and urinary
      NGAL levels and GFR were as follows: urine protein and urinary NGAL (r=0.3009,
      P=0.0256), urine protein and GFR (r=-0.6245, P<0.0001), urine microalbumin and
      urinary NGAL (r=0.1794, P=0.2275), and urine microalbumin and GFR (r=-0.5190,
      P=0.0002). CONCLUSION: From these results, we concluded that urinary NGAL is a
      reliable marker of renal function in diabetic CKD patients. However, urinary NGAL
      did not provide more accurate information regarding renal function than GFR.

PMID- 22950064
TI  - Letter: prevalence and correlates of disordered sleep in southeast asian indians
      with type 2 diabetes (diabetes metab j 2012;36:70-6).

PMID- 22950065
TI  - Response: prevalence and correlates of disordered sleep in southeast asian
      indians with type 2 diabetes (diabetes metab j 2012;36:70-6).

PMID- 22950066
TI  - Analysis of acid sphingomyelinase activity in dried blood spots using tandem mass
      spectrometry.
AB  - BACKGROUND: Niemann Pick disease (NP) is a rare, lysosomal storage disorder due
      to deficiency of the intra-lysosomal enzyme acid sphingomyelinase (ASM) resulting
      in intracellular accumulation of sphingomyelin. We evaluated a tandem mass
      spectrometry (MS/MS) method to analyze ASM activity in dried blood spots (DBS)
      that may be suitable for laboratory diagnosis of NP including high throughput
      screening of at-risk populations and potentially for newborn screening. METHODS:
      ASM activity was measured in 3.2 mm punches from DBS. The eluate was incubated
      with the ASM substrate (N-Hexanoyl-D-erythro-sphingosylphosphorylcholine [C6
      sphingomyelin (C(29)H(59)N(2)O(6)P)]) and an internal standard (N-butyroyl-D
      erythro-sphingosine [C4-ceramide (C(22)H(43)NO(3))]). ASM product and IS were
      analyzed using MS/MS in multiple reaction monitoring mode for transitions m/z
      370.6>264.3 (ASM internal standard) and m/z 398.6>264.3 (ASM product). RESULTS:
      ASM activities were stable for up to 2 months at or below 4C. Position of the
      punch in the DBS and/or hematocrit of the DBS had a limited effect on ASM
      activities. Both intra- and inter-assay variability were below 10%. There was no
      carry-over. The median ASM activity in 2,085 newborn infants was 9.5 umol/h/L
      (mean 10.6) with a SD of 5.06 umol/h/L. Six of 2,085 (0.3%) infants were found to
      have ASM activities below the cut-off of 2.5 umol/h/L. ASM activities were below
      the cut-off level in all 10 previously diagnosed cases with NP (range: 0.16 to
      2.08 umol/h/L). CONCLUSIONS: This MS/MS method for the measurement of ASM
      activity in DBS is robust and suitable for laboratory diagnosis of NP.

PMID- 22950067
TI  - AbaR7, a genomic resistance island found in multidrug-resistant Acinetobacter
      baumannii isolates in Daejeon, Korea.
AB  - BACKGROUND: Acinetobacter baumannii resistance islands (AbaRs) have been recently
      recognized as mobile genetic elements that harbor multiple resistance
      determinants and are associated with multidrug resistance (MDR). In the present
      study, we aimed to determine the AbaRs conferring multiple antimicrobial
      resistance and their clonal relatedness to MDR A. baumannii clinical isolates
      obtained from a university hospital in Daejeon, Korea. METHODS: This study
      included 29 MDR A. baumannii strains isolated in Daejeon, Korea. The minimal
      inhibitory concentrations (MICs) were determined by Etest. A. baumannii isolates
      were characterized using the 2 multiplex PCR assays and multilocus sequence
      typing (MLST) scheme. To detect and characterize AbaRs, PCR and PCR mapping
      experiments were performed. RESULTS: Twenty-seven of the 29 isolates belonged to
      the European (EU) clone II lineage and contained 5 sequence types (STs) (75, 92,
      137, 138, and 357). In this study, ST357 was confirmed for the first time in
      Korea. Only 2 of the 29 isolates belonged to the EU clone I lineage, and were
      confirmed as ST109. These 2 isolates harbored the 22-kb AbaR7 aacC1-orfP-orfQ
      aadA1 gene cassette array. In contrast, AbaR was not found in EU clone II
      isolates. CONCLUSIONS: This is the first study that attempted to determine the
      AbaRs in MDR A. baumannii isolates in Korea. We found 2 EU clone I isolates
      (ST109) that harbored AbaR7.

PMID- 22950068
TI  - Clinical usefulness of cell-based indirect immunofluorescence assay for the
      detection of aquaporin-4 antibodies in neuromyelitis optica spectrum disorder.
AB  - BACKGROUND: The presence of antibodies to aquaporin-4 (AQP4) has been identified
      as a key characteristic of neuromyelitis optica spectrum disorder (NMOSD), an
      autoimmune inflammatory demyelinating central nervous system (CNS) disorder. We
      evaluated the performance of a cell-based indirect immunofluorescence assay
      (CIIFA) for detecting AQP4 antibodies using antigen prepared with a recombinant
      AQP4 peptide transfection technique and assessed the usefulness of CIIFA for
      diagnosis of NMOSD in routine clinical practice. METHODS: Forty-six serum samples
      from 36 patients as a comparison set and another 101 patients enrolled
      consecutively from a neurology clinic were included. CIIFA and fluorescence
      immunoprecipitation assays (FIPA) were performed. CIIFA was performed at 2
      different institutions for comparison purposes. RESULTS: CIIFA and FIPA
      sensitivity in the comparison set was 86% and 79% in neuromyelitis optica (NMO)
      patients and 55% and 36% in high-risk NMO patients, respectively. The
      semiquantitative titer measured by CIIFA correlated well with the arbitrary unit
      (fluorescence units [FU]) derived from FIPA (r=0.66). Titers measured by CIIFA
      and FIPA were elevated in NMO patients compared to high-risk NMO patients (1:240
      vs. 1:180 and 8,390 vs. 4,059 FU, respectively). The frequency of AQP4 antibody
      detection by CIIFA in 101 consecutively enrolled patients was 100% in NMO and 23%
      in high-risk NMO patients, while only 4.6% in control patients, including those
      with multiple sclerosis. CONCLUSIONS: Detection of AQP4 antibodies by CIIFA
      provides sensitive and highly specific diagnostic information for NMO and high
      risk NMO patients, which can be used to differentiate these conditions from other
      demyelinating CNS diseases.

PMID- 22950069
TI  - Changes in the levels of interleukins 6, 8, and 10, tumor necrosis factor alpha,
      and granulocyte-colony stimulating factor in Korean burn patients: relation to
      burn size and postburn time.
AB  - BACKGROUND: Major burn injury induces an inflammatory response that is
      accompanied by the release of various cytokines. We investigated the gradual
      changes in the levels of pro-inflammatory and anti-inflammatory cytokines
      following burn injury and determined the relationship between these levels and
      burn size in adult Korean patients with burn injury. METHODS: Blood samples from
      9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7,
      14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL
      10, tumor necrosis factor (TNF)-alpha, and granulocyte-colony stimulating factor
      (G-CSF) were measured. Burn patients were divided into 3 groups according to burn
      size (15-30%, 31-50%, >50% total body surface area), and the concentrations of
      the cytokines were compared between these groups and the control group over 3
      weeks. RESULTS: Compared to their levels in controls, IL-6, IL-8, IL-10, TNF
      alpha, and G-CSF levels in burn patients were significantly higher during the
      observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time
      point increased with burn size, although peak levels and time to peak levels of
      these cytokines differed from patient to patient. CONCLUSIONS: These findings
      indicate that IL-6, IL-8, IL-10, TNF-alpha, and G-CSF are important mediators in
      inflammatory changes after burn injury; however, various factors, including burn
      size, may influence the concentrations of these cytokines.

PMID- 22950070
TI  - New decision criteria for selecting delta check methods based on the ratio of the
      delta difference to the width of the reference range can be generally applicable
      for each clinical chemistry test item.
AB  - BACKGROUND: Many laboratories use 4 delta check methods: delta difference, delta
      percent change, rate difference, and rate percent change. However, guidelines
      regarding decision criteria for selecting delta check methods have not yet been
      provided. We present new decision criteria for selecting delta check methods for
      each clinical chemistry test item. METHODS: We collected 811,920 and 669,750
      paired (present and previous) test results for 27 clinical chemistry test items
      from inpatients and outpatients, respectively. We devised new decision criteria
      for the selection of delta check methods based on the ratio of the delta
      difference to the width of the reference range (DD/RR). Delta check methods based
      on these criteria were compared with those based on the CV% of the absolute delta
      difference (ADD) as well as those reported in 2 previous studies. RESULTS: The
      delta check methods suggested by new decision criteria based on the DD/RR ratio
      corresponded well with those based on the CV% of the ADD except for only 2 items
      each in inpatients and outpatients. Delta check methods based on the DD/RR ratio
      also corresponded with those suggested in the 2 previous studies, except for 1
      and 7 items in inpatients and outpatients, respectively. CONCLUSIONS: The DD/RR
      method appears to yield more feasible and intuitive selection criteria and can
      easily explain changes in the results by reflecting both the biological variation
      of the test item and the clinical characteristics of patients in each laboratory.
      We suggest this as a measure to determine delta check methods.

PMID- 22950071
TI  - Evaluation of the Xpert Clostridium difficile assay for the diagnosis of
      Clostridium difficile infection.
AB  - Infection with Clostridium difficile is a growing concern because of the
      increasing prevalence and spread of nosocomial infections. Emergence of the
      hypervirulent 027/NAP1/BI strain is also notable. Existing diagnostic methods
      have low sensitivity or are time-consuming. Therefore, establishing a rapid and
      accurate microbiological diagnostic assay is needed. We evaluated the Xpert C.
      difficile assay (Xpert CD assay; Cepheid, USA) to detect toxigenic C. difficile.
      This assay is a real-time multiplex PCR assay that can be used to detect
      toxigenic C. difficile strains and differentiate the C. difficile presumptive
      027/NAP1/BI strain. A total of 253 loose stool specimens were collected and
      toxigenic cultures, VIDAS C. difficile A & B assays (VIDAS CDAB assay;
      bioMerieux, France), and the Xpert CD assay were performed. In comparison to
      toxigenic cultures, the sensitivity, specificity, and positive and negative
      predictive values were 100%, 94.6%, 83.1%, and 100%, respectively, for the Xpert
      CD assay and 40.8%, 98.0%, 100%, and 88.9%, respectively, for VIDAS CDAB assay.
      Because of the low prevalence of the PCR ribotype 027 in Korea, the evaluation of
      the usefulness of the Xpert CD assay for screening for the 027 strain was
      limited. The Xpert CD assay provides great sensitivity in diagnosing toxigenic C.
      difficile infection. In addition, this method has excellent usability because it
      is simple and fast.

PMID- 22950072
TI  - Multiplex PCR for rapid detection of genes encoding class A carbapenemases.
AB  - In recent years, there have been increasing reports of KPC-producing Klebsiella
      pneumoniae in Korea. The modified Hodge test can be used as a phenotypic
      screening test for class A carbapenamase (CAC)-producing clinical isolates;
      however, it does not distinguish between carbapenemase types. The confirmation of
      type of CAC is important to ensure optimal therapy and to prevent transmission.
      This study applied a novel multiplex PCR assay to detect and differentiate CAC
      genes in a single reaction. Four primer pairs were designed to amplify fragments
      encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR
      detected all genes tested for 4 CAC families that could be differentiated by
      fragment size according to gene type. This multiplex PCR offers a simple and
      useful approach for detecting and distinguishing CAC genes in carbapenem
      resistant strains that are metallo-beta-lactamase nonproducers.

PMID- 22950073
TI  - Detection of RUNX1-MECOM fusion gene and t(3;21) in a very elderly patient having
      acute myeloid leukemia with myelodysplasia-related changes.
AB  - An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes
      (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet
      counts of 27 * 10(9)/L, and white blood cell counts of 85.33 * 10(9)/L with 55%
      blasts. Peripheral blood samples were used in all the tests, as bone marrow
      examination could not be performed because of the patient's extremely advanced
      age and poor general health condition. Flow cytometric analysis, chromosome
      analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC
      resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this
      is the second most elderly de novo AML patient associated with t(3;21) to be
      reported.

PMID- 22950074
TI  - Quinolone-resistant Shigella flexneri isolated in a patient who travelled to
      India.
AB  - We report a recent case in which ciprofloxacin-resistant Shigella flexneri was
      isolated from a 23-yr-old female patient with a history of travel to India. Prior
      to her admission to our internal medicine department, she experienced symptoms of
      high fever and generalized weakness from continuous watery diarrhea that
      developed midway during the trip. S. flexneri was isolated from the stool
      culture. Despite initial treatment with ciprofloxacin, the stool cultures
      continued to show S. flexneri growth. In the susceptibility test for antibiotics
      of the quinolone family, the isolate showed resistance to ciprofloxacin (minimum
      inhibitory concentration [MIC], 8 ug/mL), norfloxacin (MIC, 32 ug/mL), ofloxacin
      (MIC, 8 ug/mL), nalidixic acid (MIC, 256 ug/mL), and intermediate resistance to
      levofloxacin (MIC, 4 ug/mL). In molecular studies for quinolone resistance
      related genes, plasmid borne-quinolone resistance genes such as qnrA, qnrB, qnrS,
      aac(6')-Ib-cr, qepA, and oqxAB were not detected. Two mutations were observed in
      gyrA (248C->T, 259G->A) and 1 mutation in parC (239G->T). The molecular
      characteristics of the isolated S. flexneri showed that the isolate was more
      similar to the strains isolated from the dysentery outbreak in India than those
      isolated from Korea.

PMID- 22950075
TI  - First Korean case of Robinsoniella peoriensis bacteremia in a patient with
      aspiration pneumonia.
AB  - Robinsoniella peoriensis has recently been identified as a Gram-positive, spore
      forming, anaerobic rod originally recovered from swine manure storage pits. To
      date, 6 cases of R. peoriensis infection have been reported, including 2 cases of
      bacteremia, 1 of abdominal fluid collection, and 3 of wound infection. In the
      present study, we report a 76-yr-old man with R. peoriensis bacteremia who
      developed aspiration pneumonia. Gram staining of a purified colony revealed Gram
      positive, rod-shaped bacteria. Biochemical identification using API 20 A
      (bioMerieux, France) indicated presence of Clostridium spp. We performed both 500
      bp and full-gene sequencing of 16S rRNA of the isolate. The sequence was analyzed
      with MicroSeq ID 16S rRNA Library v2.0 (Applied Biosystems, USA), GenBank Basic
      Local Alignment Search Tool (BLAST) (http://www.ncbi.nlm.nih.gov/genbank), and
      EzTaxon database v2.1 (http://www.eztaxon.org). The 500-bp 16S rRNA sequence of
      the blood culture isolate showed 99.16-99.79% similarity with R. peoriensis and
      the full-gene 16S rRNA sequence showed 98.87-99.50% similarity with R.
      peoriensis. The organism was confirmed as R. peoriensis by using all of the
      mentioned databases except for MicroSeq, which did not include the RNA sequence
      of this bacterium. This case suggests that identification of R. peoriensis might
      be challenging in clinical laboratories with no access to molecular methods, as
      certain commercial identification systems may not identify, or may misidentify,
      this organism. To the best of our knowledge, this is the first report of the
      isolation of R. peoriensis in Korea.

PMID- 22950076
TI  - Molecular identification of Schizophyllum commune as a cause of allergic fungal
      sinusitis.
AB  - Schizophyllum commune, a basidiomycetous fungus, rarely causes disease in humans.
      We report a rare case of allergic fungal sinusitis caused by S. commune in a 14
      yr-old girl. The patient presented with nasal obstruction and a purulent nasal
      discharge. Materials obtained during endoscopic surgery of the frontal recess
      revealed allergic mucin and a few fungal hyphae. A potato dextrose agar (PDA)
      culture from the allergic mucin yielded a rapidly growing white woolly mold.
      Although no distinctive features including hyphae bearing spicules or a clamp
      connection were present, the case isolate disclosed compatible mycological
      features including growth at 37C, susceptibility to cycloheximide, and production
      of a tart and disagreeable smell. S. commune was confirmed by sequence analysis
      of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal
      DNA. We believe this is the first report of allergic fungal sinusitis caused by
      S. commune in Korea. Moreover, this report highlights the value of gene
      sequencing as an identification tool for non-sporulating isolates of S. commune.

PMID- 22950077
TI  - A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal
      diagnosis.
AB  - Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems.
      Genetic testing, including prenatal testing, is a prerequisite for the diagnosis
      of many clinical conditions. However, genetic testing is complicated for FA
      because there are often many genes that are associated with its development, and
      large deletions, duplications, or sequence variations are frequently found in
      some of these genes. This study describes successful genetic testing for
      molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and
      his family in Korea. We analyzed all exons and flanking regions of the FANCA,
      FANCC, and FANCG genes for mutation identification and subsequent prenatal
      diagnosis. Multiplex ligation-dependent probe amplification analysis was
      performed to detect large deletions or duplications in the FANCA gene. Molecular
      analysis revealed two mutations in the FANCA gene: a frameshift mutation
      c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were
      separately inherited from each parent, c.2546delC was derived from the father,
      whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were
      c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the
      first report of genetic testing that was successfully applied to molecular
      diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in
      Korea.

PMID- 22950078
TI  - Contribution of gold nanoparticles to the signal amplification in surface plasmon
      resonance.
AB  - Gold nanoparticle labelling has been shown to produce a remarkable improvement in
      sensitivity for small molecule detection based on Surface Plasmon Resonance (SPR)
      bio-sensing. The LSPR (localised SPR)-SPR coupling effect and size/mass-material
      properties associated with gold nanoparticles are the two main factors to change
      the SPR resonance condition and cause the enhancement. In this paper we examine
      the separation of these factors in the context of a classical SPR bio-interaction
      assay format, and consider the implications on the design of biodetection systems
      to maximise response. The coupling effect plays a distance dependent role, which
      allows it to be mapped. The dominant enhancement associated with this factor only
      occurs within ~8 nm for a 20 nm gold nanoparticle and is changing by ~7 nm
      wavelength shift/nm distance from the Au SPR thin film. Beyond this distance, the
      size/mass associated with the nanoparticle itself dominates the enhancement. This
      is demonstrated in a 20-mer DNA sequence sandwich detection, where the
      enhancement ratio between the coupling effect and the mass is ~1.5 : 1. This
      simple method for deconvolution of the mass and coupling effects allows
      consideration of formats with LSPR nanoparticle labelling for small molecule
      detection and the best design of the labelling geometry.

PMID- 22950079
TI  - Network generation enhances interpretation of proteomics data sets by a
      combination of two-dimensional polyacrylamide gel electrophoresis and matrix
      assisted laser desorption/ionization-time of flight mass spectrometry.
AB  - Recent advances in proteomic technologies have enabled us to create detailed
      protein-protein interaction maps in diseases. As the size of the interaction
      dataset increases, powerful computational methods are required in order to
      effectively interpret network models from large scale interactome data. In this
      study, we carried out comparative proteomics to construct and identify the
      proteins networks associated with hepatic injury (HI) which are largely unknown,
      as a case study. All proteins expressed were separated and identified by two
      dimensional gel electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization time-of-flight-time-of-flight mass spectrometry (MALDI
      TOF/TOF MS). Protein-interacting networks and pathways were mapped using STRING
      analysis program. We have performed for the first time a comprehensive profiling
      of changes in protein expression of HI rats, to uncover the networks altered by
      treated with CCl(4). Identification of fifteen spots (seven over-expressed and
      eight under-expressed) were established by MALDI-TOF/TOF MS. These proteins were
      subjected to functional pathway analysis using STRING software for better
      understanding of the biological context of the identified proteins. It suggested
      that modulation of multiple vital physiological pathways including DNA repair
      process, cell apoptosis, oxidation reduction, signal transduction, metabolic
      process, intracellular signaling cascade, regulation of biological processes,
      cell communication, regulation of cellular process, and molecular transport. In
      summary, the present study provides the first protein-interacting network maps
      and novel insights into the biological responses and potential pathways of HI.
      The generation of protein interaction networks clearly enhances the
      interpretation of proteomic data, particularly in respect of understanding
      molecular mechanisms of panel protein biomarkers.

PMID- 22950080
TI  - Direct detection of peptides and small proteins in fingermarks and determination
      of sex by MALDI mass spectrometry profiling.
AB  - Matrix Assisted Laser Desorption Ionisation Mass Spectrometry (MALDI MS) can
      detect and image a variety of endogenous and exogenous compounds from latent
      fingermarks. This opportunity potentially provides investigators with both an
      image for suspect identification and chemical information to be used as
      additional intelligence. The latter becomes particularly important when the
      fingermark is distorted or smudged or when the suspect is not a previously
      convicted offender and therefore their fingerprints are not present in the
      National Fingerprint Database. One of the desirable pieces of intelligence would
      be the sex of the suspect from the chemical composition of a fingermark. In this
      study we show that the direct detection of peptides and proteins from fingermarks
      by MALDI MS Profiling (MALDI MSP), along with the multivariate modeling of the
      spectra, enables the determination of sex with 85% accuracy. The chemical
      analysis of the fingermark composition is expected to additionally provide
      information on traits such as nutritional habits, drug use or hormonal status.

PMID- 22950081
TI  - First magnets based on thiocyanato-bridges.
AB  - 2-D NCS-bridged {3d-4d} molecule-based magnets, formed by reaction of
      [Mo(III)(NCS)(6)](3-) with either Ni(II) or Co(II) complexes, have been found to
      exhibit magnetic ordering with T(C) = 39 K for {Co(3)Mo(2)} while {Ni(3)Mo(2)}
      has a non-magnetic ground state as a result of exact compensation by the
      individual sub-lattices.

PMID- 22950082
TI  - Rechargeable battery-triggered electrochemiluminescence detection on microfluidic
      origami immunodevice based on two electrodes.
AB  - A low-cost, portable rechargeable battery was firstly used to fabricate a battery
      triggered, screen-printed two-electrode electrochemiluminescent immunoassay on a
      3D microfluidic origami electronic device.

PMID- 22950083
TI  - Cooperativity of H-bonding and anion-pi interaction in the binding of anions with
      neutral pi-acceptors.
AB  - A rare anion-pi complex between bromide and a neutral receptor is reported and
      related receptor systems are studied with a series of anions. The interaction is
      observed in the solid state and in solution, and further evidence for it is
      obtained by a computational study.

PMID- 22950084
TI  - A bifunctional luminescent single-ion magnet: towards correlation between
      luminescence studies and magnetic slow relaxation processes.
AB  - A new heterodinuclear [Zn(L)Dy](3+) complex, with L being a compartmental Schiff
      base ligand, exhibits the characteristic Dy(3+) luminescence associated with a
      single-ion field induced slow relaxation of the magnetisation. This complex may
      be considered as one of the rare examples of a bifunctional luminescent single
      ion magnet.

PMID- 22950085
TI  - Point-to-helical chirality transfer for a scalable and resolution-free synthesis
      of a helicenoidal DMAP organocatalyst.
AB  - The synthesis of a second-generation [6]-helicenoidal DMAP organocatalyst is
      reported. The synthesis is reliant upon a highly diastereoselective Rh-catalysed
      [2 + 2 + 2] triyne cycloisomerization, using an existing stereocentre to control
      the sense of forming helicity. Taken together, a scalable (>1 g), resolution-free
      entry to a helical DMAP with the capacity for subsequent functionalization, has
      been achieved.

PMID- 22950086
TI  - Local orientational disorder in peptide fibrils probed by a combination of
      residue-specific 13C-18O labelling, polarised infrared spectroscopy and molecular
      combing.
AB  - A novel combination of site-specific isotope labelling, polarised infrared
      spectroscopy and molecular combing reveals local orientational ordering in the
      fibril-forming peptide YTIAALLSPYSGGRADS. Use of (13)C-(18)O labelled alanine
      residues demonstrates that the N-terminal end of the peptide is incorporated into
      the cross-beta structure, while the C-terminal end shows orientational disorder.

PMID- 22950087
TI  - Curcumin and inflammatory bowel disease: biological mechanisms and clinical
      implication.
AB  - Increased recognition of the limits of conventional medicine has helped drive the
      growing interest in complementary and alternative medicine which is now being
      commonly used in patients with chronic diseases, including individuals with
      Crohn's disease and ulcerative colitis. Recently, scientific interest has
      unraveled the beneficial pharmacological effects of curcumin. We present an
      updated concise review of currently available in vitro, animal and clinical
      studies demonstrating the therapeutic effect of herbal medication in inflammatory
      bowel disease.

PMID- 22950088
TI  - Exercise is good for pregnant women and safe for the fetus.

PMID- 22950089
TI  - Red wine may decrease endogenous estrogen levels in premenopausal women, but does
      this protect against breast cancer?

PMID- 22950090
TI  - Drink tea for bone health but not too much.

PMID- 22950091
TI  - An updated scientific review of the benefits of breastfeeding with additional
      resources for use in everyday practice.

PMID- 22950092
TI  - More research needed on acceptability and safety of nicotine patches in pregnancy
      for smoking cessation.

PMID- 22950093
TI  - Misconceptions in interpretation of antimicrobial resistance data.

PMID- 22950094
TI  - The vexed question of race-based admission to medical school.

PMID- 22950095
TI  - Pretoria intervention saves E Cape health corruption buster.

PMID- 22950096
TI  - System burning out our doctors.

PMID- 22950097
TI  - Discovery to tighten disclosure protocol on new device.

PMID- 22950098
TI  - SA men-time for introspection/renewed action?

PMID- 22950099
TI  - Images of the month: the reduviid bug travels north: an impressive manifestation
      of megaesophagus.

PMID- 22950100
TI  - Naturally occurring antibodies.

PMID- 22950101
TI  - [Therapeutic ultrasound clarifies suspicion].

PMID- 22950102
TI  - [Does it help to have your own serum for osteochondral lesions?].

PMID- 22950103
TI  - [Early mobilization: painful and unnecessary?].

PMID- 22950104
TI  - [Sports-what exactly does the fetus say?].

PMID- 22950105
TI  - [Does sport promote fertility?].

PMID- 22950106
TI  - [Marathon runners are resistant to advice].

PMID- 22950107
TI  - [Suspected hamstring tendinopathy? Pain provocation!].

PMID- 22950108
TI  - [Standard ECG criteria help in diagnosis].

PMID- 22950110
TI  - [Sports and energy drinks are attacking tooth enamel].

PMID- 22950109
TI  - [Music soothes diurnal muscle fluctuation].

PMID- 22950111
TI  - [New research - Researchers targeting stem cells to bone].

PMID- 22950112
TI  - [Osteoarthritis - glucosamine does not combine with coumarins].

PMID- 22950113
TI  - [Heterozygous sickle cell anemia increases risk of death from overload].

PMID- 22950114
TI  - [Sudden death - registry for prevention].

PMID- 22950115
TI  - [Carpal tunnel syndrome - ultrasound avoids complications].

PMID- 22950117
TI  - Class, health, and the American elections.

PMID- 22950116
TI  - [Manual-medical differential diagnosis of low back pain including osteopathic
      procedures].
AB  - The differential diagnostic evaluation of painful functional disorders of the
      lumbosacral and lumbopelvic region, i. e. the so-called "low back pain" is very
      extensive, but is often reduced to the question of chronicity. The manual medical
      diagnosis can make a valuable contribution in such cases for determination of
      structural and functional pathology. Early application of manual medical
      therapies seems to be effective for peracute complaints. The mobilization of
      restrictions of the pelvic visceral attachments should be included. In the
      following review manual medical syndromes are presented that summarize the
      findings from the musculoskeletal and visceral system. This is intended to
      facilitate the primary differential diagnostic evaluation, as well as treatment
      planning. The combination with osteopathic methods is very profitable. A
      necessary specialist differential diagnosis remains essential.

PMID- 22950118
TI  - Days of the giants: remembering Robert F Loeb.

PMID- 22950119
TI  - Climacteric commentaries.  Sexual activity and satisfaction in community-dwelling
      older women.

PMID- 22950120
TI  - Climacteric commentaries. Statin use and the risk for diabetes mellitus.

PMID- 22950121
TI  - Climacteric commentaries. Better sleep but higher mortality risk.

PMID- 22950122
TI  - Climacteric commentaries. Cognitive behavior therapy for treatment of hot
      flushes.

PMID- 22950123
TI  - Climacteric commentaries.  SSRIs for hot flushes and insomnia.

PMID- 22950124
TI  - Climacteric commentaries. Physical activity across adulthood maintains physical
      capability in midlife.

PMID- 22950125
TI  - Climacteric commentaries.  Simple ovarian cysts in postmenopausal women: scope of
      conservative management.

PMID- 22950126
TI  - [MPFL reconstruction after first luxation ].

PMID- 22950127
TI  - [Not Available].

PMID- 22950128
TI  - Guest editorial: bioinformatics and computational systems biology.

PMID- 22950130
TI  - [Not Available].

PMID- 22950129
TI  - Guest editors' introduction to the special section on bioinformatics research and
      applications.

PMID- 22950131
TI  - [Don't forget to apply!].

PMID- 22950132
TI  - [Not Available].

PMID- 22950133
TI  - [Not Available].

PMID- 22950134
TI  - [Radiotherapy treatment is highly effective in all stages].

PMID- 22950135
TI  - [The "Hegar test" facilitates detection of a dystopic suburethral band].

PMID- 22950136
TI  - [The dream of eternal youth].
AB  - Eugen Steinach (1861-1944) was one of the best known hormone researchers in the
      early 20th century. Above all he was famous for his work in the field of sexual
      physiology. Particularly controversial was his method of transplanting testicles
      under the abdominal wall that was supposed to lead to the patient's rejuvenation.

PMID- 22950137
TI  - [Misunderstandings - man has 4 ears].

PMID- 22950138
TI  - [GKV - health care structure regulation - challenges and risks].

PMID- 22950139
TI  - Bibliography. Movement disorders. Current world literature.

PMID- 22950140
TI  - [Early diagnosis of excessive stress and depression at health examination and the
      future prospect].

PMID- 22950141
TI  - [From mental health examination to post-diagnosis guidance at occupational health
      services--a report on the outcome of the implementation of the 2010 mental health
      service by the National Labor Hygiene Alliance].

PMID- 22950143
TI  - [Management of problems related to suicide and mental health].

PMID- 22950142
TI  - [Toward a revision of the Occupational Health and Safety Law for mental health
      improvement].

PMID- 22950144
TI  - Sharing information between the Department of Veterans Affairs and the Department
      of Defense. Final rule.
AB  - This document adopts as final, without change, the interim final rule published
      in the Federal Register on October 20, 2011. This final rule removes a Department
      of Veterans Affairs (VA) regulatory restriction on the sharing of certain medical
      information with the Department of Defense (DoD) that is not required by the
      applicable statute and is inconsistent with the intent and purpose of that
      statute.

PMID- 22950145
TI  - Service dogs. Final rule.
AB  - The Department of Veterans Affairs (VA) amends its regulations concerning
      veterans in need of service dogs. Under this final rule, VA will provide to
      veterans with visual, hearing, or mobility impairments benefits to support the
      use of a service dog as part of the management of such impairments. The benefits
      include assistance with veterinary care, travel benefits associated with
      obtaining and training a dog, and the provision, maintenance, and replacement of
      hardware required for the dog to perform the tasks necessary to assist such
      veterans.

PMID- 22950146
TI  - Administrative simplification: adoption of a standard for a unique health plan
      identifier; addition to the National Provider Identifier requirements; and a
      change to the compliance date for the International Classification of Diseases,
      10th Edition (ICD-10-CM and ICD-10-PCS) medical data code sets. Final rule.
AB  - This final rule adopts the standard for a national unique health plan identifier
      (HPID) and establishes requirements for the implementation of the HPID. In
      addition, it adopts a data element that will serve as an other entity identifier
      (OEID), or an identifier for entities that are not health plans, health care
      providers, or individuals, but that need to be identified in standard
      transactions. This final rule also specifies the circumstances under which an
      organization covered health care provider must require certain noncovered
      individual health care providers who are prescribers to obtain and disclose a
      National Provider Identifier (NPI). Lastly, this final rule changes the
      compliance date for the International Classification of Diseases, 10th Revision,
      Clinical Modification (ICD-10-CM) for diagnosis coding, including the Official
      ICD-10-CM Guidelines for Coding and Reporting, and the International
      Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS)
      for inpatient hospital procedure coding, including the Official ICD-10-PCS
      Guidelines for Coding and Reporting, from October 1, 2013 to October 1, 2014.

PMID- 22950147
TI  - Labor market effects of the Massachusetts health insurance reform.

PMID- 22950148
TI  - Are consumers forward-looking in responding to health care prices?

PMID- 22950150
TI  - [Advances in airway humidification during mechanical ventilation].

PMID- 22950149
TI  - [Isolation and characterization of human alveolar type II cells and phenotypes
      maintaining study].
AB  - OBJECTIVE: To establish a method of isolate, purify, primary culture and identify
      human alveolar type II cells (AT II ) in vitro, as well as its possible
      maintaining phenotype characteristics. METHODS: The marginal lung tissue was
      collected. AT II cells were isolated with trypsin and elastase, purified by a
      series of steps, such as, cell sieve filtration, differential adhesion, gradient
      separation and anti-CD14 beads separation. AT II cells were identified with
      immunofluorescence of human pro-surfactant-associated protein C (pro-SP-C), Green
      DND-26 probe and electron microscope. The purity of AT II cells was measured by
      immunofluorescence of human pro-SP-C and Green DND-26 probe. The viability of AT
      II cells was measured by trypan blue staining. The phenotypes (SP-A, SP-B,SP-C,
      SP-D) were monitored with reverse transcription-polymerase chain reaction (RT
      PCR) at different time points. RESULTS: The output of AT II cells from lung
      tissue was (5-10) x 105/g, and the cell viability was (93 +/- 2)% with trypan
      blue staining, the cell purity was about 98% with pro-SP-C immunofluorescence and
      Green DND-26 fluorescent probe, the lamellar bodies were clearly observed with
      transmission electron microscope. In the aspect of phenotypes maintaining, the
      time of surfactant expression was about 24 days [SP-A: 0.52 + 0.03 (day 16), 0.35
      + 0.02 (day 20),0.26 +/- 0.01 (day 24), 0.10 + 0.08 (day 28); SP-C: 0.68 0.16
      (day l6), 0.31 + 0.04 (day 20), 0.18 + 0.06 (day 24), 0.14 + 0.09 (day 28)], and
      the longest one was more than 28 days [SP-B: 1.05 + 0.17 (day 16), 0.76 +
      0.35(day 20), 0.55 0.15 (day 24), 0.36 0.19 (day 28); SP-D: 0.52 0.19 (day 16),
      0.33 + 0.12 (day 20), 0.31 +0.04 (day 24), 0.23 +/- 0.02 (day 28)). CONCLUSION:
      We successfully established a procedure to separate, purify,identify of AT II
      cells, which retain primary phenotypic characteristics over long period.

PMID- 22950151
TI  - Food animal producer pledge should be developed to match pet owner pledge.

PMID- 22950152
TI  - Distributed teaching methods.

PMID- 22950153
TI  - Visions of the future: NRC study advances debate about veterinary medicine in the
      21st century.

PMID- 22950155
TI  - VCPR definition could change.

PMID- 22950154
TI  - On the right path: Study reinforces current efforts to help profession.

PMID- 22950156
TI  - Border violence complicates animal health surveillance: port-of-entry facilities
      moved for safety reasons.

PMID- 22950157
TI  - White-nose fungus found in endangered Tenn. bats.

PMID- 22950158
TI  - Judge orders antimicrobial safety evaluation.

PMID- 22950159
TI  - [Suicide prevention and mental health].

PMID- 22950160
TI  - [Cooperation between general and psychiatric emergency health personnel in the
      approach to suicide prevention].

PMID- 22950161
TI  - [On clinical diagnosis of depression].
AB  - In this paper, diagnosis of depression was deliberatively considered from a view
      of psychopathological studies, and problems of operational diagnostic system in
      psychiatry were discussed. For good clinical practices, 1) diagnosis must be
      considered as a part of clinical practices. 2) diagnosis must be closely related
      to therapeutic works, 3) the process of making a diagnosis itself should be
      managed to be remedial, and 4) a clinical category is expected to contain not
      only a summation of individual cases, and at the same time the link between the
      category and individual cases should not be abandoned. The author also discussed
      about some clinical maneuvers.

PMID- 22950162
TI  - [Choosing the adequate antidepressant focusing on efficacy, tolerability and its
      predictors].
AB  - Major depressive disorder is a debilitating disease that imposes significant
      burden not only on patients but also on society for its high prevalence and
      association with serious consequences such as suicide and substantial negative
      impact on social health, with both direct and indirect considerable costs
      worldwide. Selective serotonin reuptake inhibitors (SSRIs) treatment was
      introduced 12 years ago and reduced morbidity of major depressive disorder with a
      favorable side effect profile. However, unfortunately, not all individuals
      benefit from treatment and 30-40% of patients do not show a complete response to
      treatment. Clinical guideline does not show which antidepressant is the most
      appropriate to the patient just in front of you in clinical setting but simply
      suggest 'use the new antidepressant such as SSRI, SNRI, mirtazapine as first line
      therapy' or 'be vigilant for side effect'. In this paper, I summarized the
      considerable evidence such as meta-analysis, guideline and double blind
      randomized controlled trial to detect the most appropriate pharmacotherapy as
      first-line and second or later therapy including treatment resistant depression
      from the some specific factors point of view; specific feature of symptom,
      ethnicity and genetic feature.

PMID- 22950163
TI  - [Treatment of depression using transcranial stimulation (TMS)and neuroimaging].
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive technique for
      stimulating the cerebral cortex and altering cortical and subcortical activities.
      High-frequency stimulation (5-20 Hz) has been shown to enhance cortical
      excitability, and low-frequency stimulation (1 Hz) to inhibit cortical
      excitability. High-frequency stimulation over the left dorsolateral prefrontal
      cortex (DLPFC) and low-frequency stimulation over the right DLPFC have both been
      shown to be antidepressant effects in the treatment of depression. Our previous
      studies have revealed that high-frequency stimulation over the left DLPFC
      increases cerebral blood flow (CBF) in the left prefrontal cortex, orbitofrontal
      cortex, anterior cingulate, and subcallosal area (subgenual cingulate cortex)
      with improvement of depression, and low-frequency stimulatin over the right DLPFC
      decreases CBF in the right prefrontal cortex, orbitofrontal cortex, and
      subcallosal area with improvement of depression. Theses findings suggest that
      there might be differences in the antidepressant effects between high-frequency
      stimulation over the left DLPFC and low-frequency stimulation over the right
      DLPFC, raising a possibility that more appropriate approaches could be taken for
      the treatment of depression by using neuroimaging, and tailor-made medicine with
      TMS could be provided depending on each patient with depression.

PMID- 22950164
TI  - Patient satisfaction: Public engagement with service information is key test of
      choice.

PMID- 22950165
TI  - Social enterprises risk contracts axe.

PMID- 22950166
TI  - Turning the NHS into a lean, mean, healthcare machine.

PMID- 22950167
TI  - Time to push the accelerator--and change the culture.

PMID- 22950168
TI  - Innovation driving quality and value: Mind P and Q... but focus on I.

PMID- 22950169
TI  - Perspectives on innovation, health and wealth: 'We cannot rest on our laurels'.

PMID- 22950170
TI  - Supporting the NHS to deliver: Make an impact: How NHS organisations will be
      helped to implement the six high impact innovations.

PMID- 22950171
TI  - 'The challenge is massive'. Interview by Daloni Carlisle.

PMID- 22950172
TI  - Academic health science networks: Let's get practical.

PMID- 22950173
TI  - High impact innovations: Making it happen.

PMID- 22950174
TI  - Britain's sporting chance.

PMID- 22950175
TI  - Let patients into the information age.

PMID- 22950176
TI  - Converting data into currency.

PMID- 22950177
TI  - GPs on the streets?

PMID- 22950178
TI  - How to buy: car parking: Remove the barriers to your perfect vehicle.

PMID- 22950179
TI  - Determining the value of wellness programs.
AB  - Recent advances can give companies a solid set of return on investment (ROI)
      measurements on their health improvement programs, provided they are willing to
      invest in both wellness programs and measurement efforts that effectively gauge
      those programs' merit. As this article explains, choosing the right methodology
      will depend on the health improvement programs being evaluated, data and
      resources available, and the degree of precision desired by management. The
      authors discuss the different measurement methodologies and various measurement
      considerations. They conclude that using several methods and multiple iterations
      under varying sets of assumptions is often useful, not only for calculating ROI
      but also for providing companies a framework for continual program tracking and
      improvement.

PMID- 22950180
TI  - Wellness strategies for smaller businesses.
AB  - While innovative smaller companies are implementing employee wellness programs,
      many smaller firms may point to a lack of resources, such as staffing and
      financial resources, to establish and sustain a wellness program. The uncertain
      economy and rising health care costs have caused many smaller businesses to focus
      on core business strategies to keep the doors open and the business going.
      However, innovative companies realize that building a culture of health is a long
      term business strategy directly related to improving the bottom line. This
      article highlights one company's approach to wellness and the results of the
      company's programs. It also outlines the components of a successful wellness
      program and suggests practical implementation steps for smaller businesses.

PMID- 22950181
TI  - The medical home bends cost curve.
AB  - While the Affordable Care Act is trying to manage health insurance, as well as
      mandating coverage, a number of projects around the country are trying to manage
      the underlying cost of health care. By bringing back the concept of a true
      primary care physician, who provides 90% of your care and coordinates with your
      specialists, these programs are bending the curve of health care cost trends.
      Most are seeing a reduction in emergency room visits and hospital days in the
      double digits. Others that are taking fee-for-service insurance out of the
      picture altogether are experiencing even higher reduction rates. The goal is to
      increase patient health, which includes the patient having an active role in
      understanding his or her condition, treatment options and self-care strategies.
      It is estimated that if all Americans had access to a medical home, our nation
      could save $37 billion annually.

PMID- 22950182
TI  - HSA programs for groups: employer versus employee responsibilities.
AB  - Employers implementing a health savings account (HSA) program face a shared
      compliance burden with their employees. The law dictates that all HSAs are
      individual accounts that must be opened by an Internal Revenue Service (IRS)
      approved custodian or trustee. The individual account features combined with a
      required third-party custodian place much of the compliance burden for HSAs on
      the employee and custodian rather than the employer. Employees are compensated
      for the additional burden because HSAs give them more control over their health
      care money, and employers are generally pleased with their own reduced compliance
      burden. The shared compliance responsibilities, however, create confusion and
      misunderstanding for both employers and employees. This article distinguishes
      between the responsibilities of the employer and the employees for HSAs.

PMID- 22950184
TI  - Fiduciary duty. Faber v. MetLife, 648 F.3d 98, 2011 WL 3375530 (2d cir. 2011).
      Providing postdistribution banking services does not continue the ERISA fiduciary
      relationship.

PMID- 22950183
TI  - Erisa preemption. King v. BlueCross BlueShield, 439 Fed.Appx. 386, 2011 WL
      3822023 (5th Cir. 2011). ERISA preemption applies even to former beneficiaries,
      or those whose benefits have been canceled by a plan, as long as the claims
      relate to the plan.

PMID- 22950185
TI  - Amendment of health benefits. Sullivan v. CUNA Mutual, 649 F.3d 553, 2011 WL
      3487414 (7th Cir. 2011). Employer can amend health plan without violating
      anticutback rule, sick days are not plan assets.

PMID- 22950186
TI  - Scope of discovery--benefits determination. Crosby v. Louisiana health service,
      647 F. 3d 258 (5th Cir 2011). Relevant evidence may go beyond just administrative
      record.

PMID- 22950187
TI  - Intervention: South London's 'failure' leaves the big questions unanswered.

PMID- 22950189
TI  - Privately run trust tops patient satisfaction survey.

PMID- 22950188
TI  - Lansley invokes hospital failure regime.

PMID- 22950190
TI  - Patient cost could inform pricing.

PMID- 22950191
TI  - Plan B has arrived.

PMID- 22950192
TI  - End ageism and care will improve for all.

PMID- 22950194
TI  - Let's get serious about telehealth.

PMID- 22950193
TI  - Taking charge.

PMID- 22950195
TI  - Self-care: The long answer.

PMID- 22950196
TI  - Beating COPD.

PMID- 22950197
TI  - Respiratory care: Clearing obstructions.

PMID- 22950198
TI  - Respiratory care: case studies: How to get better.

PMID- 22950199
TI  - Workforce: The steps towards transition.

PMID- 22950200
TI  - Technology: a futuristic enterprise.

PMID- 22950201
TI  - Roundtable: commissioning information: Full measures.

PMID- 22950202
TI  - How to buy: clinical portals: A window of opportunity.

PMID- 22950203
TI  - General practice: Taking the nip out of the QIPP.

PMID- 22950204
TI  - Leadership framework: A single focus on leadership development.

PMID- 22950205
TI  - Commissioning: Spelling out the value in voluntary.

PMID- 22950206
TI  - Accountability: Getting right to the point.

PMID- 22950207
TI  - Leadership: Why so many vacancies? Time to stop the NHS talent drain.

PMID- 22950208
TI  - Revealed: DH warnings to pipeline laggards.

PMID- 22950209
TI  - Employers' plan targets pay of senior staff.

PMID- 22950210
TI  - Commissioning: Plans launched to integrate health and social care data.

PMID- 22950211
TI  - Spending on branded drugs expected to drop.

PMID- 22950212
TI  - Private MH hospitals facing tighter margins.

PMID- 22950213
TI  - Take the shakes out the shake-ups.

PMID- 22950214
TI  - Why the NHS and local government jigsaw can fit together this time.

PMID- 22950215
TI  - Out with the old.

PMID- 22950216
TI  - Medication errors: A safer approach to hospital pharmacy.

PMID- 22950217
TI  - Performance: A private lesson in productivity.

PMID- 22950218
TI  - Quality: Why patient leaders are the new kids on the block.

PMID- 22950219
TI  - Long-term conditions: A few words on self-management.

PMID- 22950220
TI  - Estates: Properties of a prosperous estate.

PMID- 22950221
TI  - No shortage of blame. Congress refocuses on gray market in drug shortfalls.

PMID- 22950223
TI  - Potential for success. Care, pay changes linked to cutting disparities.

PMID- 22950222
TI  - Greening hospitals. Initiative lets hospitals collaborate on 'challenges'.

PMID- 22950224
TI  - Not budging. Good news hard to find in 30-day readmissions data.

PMID- 22950225
TI  - Sour economy cited in debt downgrades.

PMID- 22950226
TI  - Out with old, in with new. Many providers switching vendors, EHR systems.

PMID- 22950227
TI  - Reform spurs dealmaking. Provisions, clarity in law clear path for partnerships.

PMID- 22950228
TI  - On the line for Mich. Blues. Decision on 'most favored nation' clauses could
      affect federal litigation.

PMID- 22950229
TI  - The early returns on accountable care. Newly minted ACOs grapple with allocating
      resources and adjusting operations to put the theory to work.

PMID- 22950230
TI  - Targeting early deliveries. Initiative helped reduce admissions of premature
      babies to NICU by 25%.

PMID- 22950231
TI  - The root of disease. Lifestyle interventions take aim at chronic ailments.

PMID- 22950232
TI  - The recruiting network. Social media sites, tools become increasingly popular on
      both sides of job search.

PMID- 22950233
TI  - 'Novel and contentious': NHS rethinks its funding options.

PMID- 22950234
TI  - Pension funds to bankroll pounds 298 m hospital in finance first.

PMID- 22950235
TI  - Bed waiting times for A&E admissions soar.

PMID- 22950236
TI  - In the new NHS, you are what you tweet.

PMID- 22950237
TI  - In the new NHS, you are what you tweet.

PMID- 22950238
TI  - CCGs need nurses' talents.

PMID- 22950239
TI  - The paper chase is on as trusts change the record.

PMID- 22950240
TI  - How to make it to merger.

PMID- 22950241
TI  - Clinical leaders. Why doctors should be bothered to lead.

PMID- 22950242
TI  - Public health. Olympic legacy of a better life.

PMID- 22950243
TI  - Partnership working. Collaborating competitive marketplace.

PMID- 22950244
TI  - CCGs face wicked choices reversing trend in GP referrals.

PMID- 22950245
TI  - Rising GP referrals contradict Lansley claim.

PMID- 22950247
TI  - Former Virgin's next conquest. Interview by Daloni Carlisle.

PMID- 22950246
TI  - Caution over social care reform funding.

PMID- 22950248
TI  - The PCT legacy.

PMID- 22950249
TI  - One day at a time.

PMID- 22950250
TI  - Towards a brighter future.

PMID- 22950251
TI  - At the heart of it.

PMID- 22950252
TI  - Welcome to higher performing healthcare.

PMID- 22950253
TI  - Trial blazers.

PMID- 22950254
TI  - Asking trusts to look at themselves under a lens.

PMID- 22950255
TI  - Getting up to date is simply essential.

PMID- 22950256
TI  - The key is in the community.

PMID- 22950257
TI  - Beyond the tickbox.

PMID- 22950258
TI  - People of the future.

PMID- 22950259
TI  - Good genes. Are we ready for inexpensive, easy access to personal DNA tests?

PMID- 22950260
TI  - Cardiac arrests. Hospitals anxious they could face hefty false claims penalties
      in implanted cardiac defibrillator cases.
AB  - Hospitals are nervously waiting to hear if False Claims Act penalties will be
      imposed on implanted defibrillator cases that don't fit Medicare guidelines. The
      Cleveland Clinic's heart program has had 264 of its cases questioned. "At the
      time, I think we made the right decision, and I don't feel at all uncomfortable
      defending that," says Bruce Lindsay, left, of the system. "I think we did the
      right thing".

PMID- 22950261
TI  - Ball is in providers' court. UDI system aims to help FDA identify problem
      products more quickly.

PMID- 22950262
TI  - Don't deny the economics. Hospice and palliative care are best for chronic
      illness, controlling costs.

PMID- 22950263
TI  - The first step. Hospice-care providers to begin reporting on two quality
      measures, and incremental approach that the industry supports.

PMID- 22950264
TI  - Care up in the air. Helicopter ambulance services save lives, but still face
      cost, safety concerns.

PMID- 22950265
TI  - Disease can't hide.

PMID- 22950266
TI  - iPad, M.D.

PMID- 22950267
TI  - [Bariatric surgery: history up to the present].

PMID- 22950268
TI  - [Gastric shunting operation for the morbid obesity treatment].

PMID- 22950269
TI  - [Biliopancreatic shunting].

PMID- 22950270
TI  - [Comparative results of various methods of surgical treatment of severe forms of
      metabolic syndrome].
AB  - The data about metabolic syndrome (MS), characteristic for interrelationship of
      the main pathogenetic factors, are adduced. Along with positive moments, the
      faults of conservative therapy for MS are described, the indications for surgical
      treatment performance were substantiated and the results of its application in
      220 patients, suffering severe forms of MS, were analyzed.

PMID- 22950271
TI  - [Peculiarities of the blood microcirculation in the anterior abdominal wall in
      patients with excessive body mass].
AB  - Investigation was conducted, using laser Doppler flowmetry (LDF) with the help of
      LAKK-02 analizator, with the objective to improve the results of surgical
      treatment and prophylaxis of complications in the postoperative wound healing in
      patients, suffering concomitant obesity. Characteristic disorders of
      microcirculation in soft tissues of the anterior abdominal wall in the operative
      intervention region were analyzed. There were examined 31 patients, suffering
      obesity stages I-III, their body mass index was (39.11 +/- 0.79) kg/m2 at
      average. Microcirculation disorders in soft tissues of the anterior abdominal
      wall have caused worsening of the postoperative period course in the patients.
      LDF is a highly informative noninvasive method, which have to be used trustworthy
      for estimation of a microcirculation bed state in the patients, suffering
      obesity.

PMID- 22950272
TI  - [Possibilities of improving of videothoracoscopic operations for spontaneous
      pneumothorax].
AB  - A 15-years experience of videothoracoscopic operations in the treatment of 616
      patients, suffering spontaneous pneumothorax, was summarized. The methods of
      videothoracoscopic operations, depending on the volume and localization of
      pathological process in pulmonary tissues, were depicted. The stages of
      endoscopic surgical intervention for spontaneous pneumothorax were analyzed. The
      disease recurrence, while using videothoracoscopic operations, have occurred in
      3.6% of patients. All the patients are alive.

PMID- 22950273
TI  - [Application of laparoscopic splenectomy in the treatment of surgical diseases of
      the spleen].
AB  - From October 2007 laparoscopic splenectomy (LS) was performed in 16 patients,
      including for thrombocytopenicpurpura--in 6, splenomegaly--in 4, hemolytic
      microsphaerocytus anemia--in 2, echinococcal splenic cysts--in 2, nonparasytic
      splenic cysts--in 2. LS solely was performed in 6 patients, while a manually
      assisted LS, using Pneumo Sleeve (the Dexterity firm) system, as well as original
      pneumosleeve of own design--in 10. The operation duration was from 110 to 220
      min. The stationary postoperative treatment duration have had constituted 2-4
      days. The first experience of LS conduction witnesses the possibility of
      successful application of the method in various surgical diseases of the spleen.

PMID- 22950274
TI  - [Coefficient of activation of the brain subcortex structures in a comatose
      state].
AB  - The brain bioelectric activity changes in patients, suffering comatose state, may
      not be revealed by electroencephalography (EEG) data. This obstacle makes
      difficult to accomplish the patient functional state estimation and restricts the
      conducted treatment efficacy. That's why there was elaborated a quantitative
      diagnostic criterion of EEG--coefficient of a subcortex activation, permitting
      precisely and objectively to estimate the changes of functional state of the
      comatose patient brain.

PMID- 22950275
TI  - [Optimization of surgical correction of varicocele in children].
AB  - The operation, named after Ivanissevich, performed in children for varicocele,
      under intraoperative phlebotesticulography, is highly effective. The venography
      method permits to prognosticate a postoperative period course, to prevent the
      disease recurrence occurrence. A surgical method, applied for varicocele
      correction has an advantages, because it includes the excision of the testis
      veins in a wide fashion together with anastomoses from the upper third of a
      lumbar portion to deep inguinal ring, to the testis vein formation region,
      permitting to omit a reason for the disease recurrence without application of
      roentgencontrast investigation. The method was used in 145 children for a left
      sided varicocele stages II-III. Complications were not observed. In terms of
      follow-up before 2 years the recurrences were not observed.

PMID- 22950276
TI  - [Intraoperative plasty of complex defects of the bones and soft tissues in a
      craniofacial region].
AB  - The results of treatment of 159 patients, suffering craniofacial region tumors,
      were analyzed. In tumoral invasion of cranial bones with affection of the head
      soft tissues the bone defects dimensions were determined and the implants
      prepared preoperatively, the soft tissues defects were closed, using
      transposition or free microsurgical transplantation of the tissues composite
      complexes. The complex approach application have permitted to close the bones and
      soft tissues defects of the head craniofacial region with achievement of
      subsequent functional and aesthetic result.

PMID- 22950277
TI  - [Changes of energy balance in patients during anesthesia].
AB  - A new method of energobiometric monitoring, which is realized, using the applied
      computeric programm, was proposed. Energobiometric monitoring permits to
      determine quantitatively the energetic deficiency level and to correct it in time
      for the perioperative morbidity minimization. The patients, suffering
      uncomplicated operational trauma, presenting in two groups and differing for the
      anesthesy method applied, have took part in the clinical investigation.

PMID- 22950278
TI  - [Experimental investigation of possibilities of the ultrasound and liquid-stream
      dissector in operations on parenchymatous organs].
AB  - The results of experimental investigations were adduced, concerning studying of
      possibilities and the outcomes analysis of the ultrasound and a liquid-stream
      dissector application while operating on parenchymatous organs. There was
      established, that while operating on liver, there was not any essential
      difference between application of the ultrasound and stream of a liquid
      concerning the achievement of a quality of the stroma elements isolation; while
      performing operations on the spleen a liquid-stream dissector have had evolved as
      a more effective one, permitting to isolate a significantly more quantity of
      unaffected elements of stroma. The hemostasis methods are the main, which
      influence the organs stump formation and the typical cellular structure
      restoration, and they must be applied, using the both methods of dissection.

PMID- 22950279
TI  - [Experience of work of the polytrauma department].

PMID- 22950280
TI  - Pack mentality.

PMID- 22950281
TI  - The buddy system. Leveraging a partnership improves hospitals' quality, lowers
      costs: report.

PMID- 22950282
TI  - Race as a risk factor. Higher mortality rates seen for white patients, but
      readmissions higher for minorities, report finds.

PMID- 22950283
TI  - Making progress. Life-expectancy gap between races decreasing.

PMID- 22950284
TI  - Go ahead--cry at work.

PMID- 22950285
TI  - How stem cells are changing the way we think about disease.

PMID- 22950286
TI  - Monitor scraps controversial restrictions.

PMID- 22950287
TI  - Non-acute services see rise in transfer delays.

PMID- 22950288
TI  - The hard data man's soft spot.

PMID- 22950289
TI  - Living within our means locally.

PMID- 22950290
TI  - The magic number for service satisfaction.

PMID- 22950291
TI  - Go fishing for the best variety of CCG for you.

PMID- 22950292
TI  - Taking control of their condition.

PMID- 22950293
TI  - Moved to the point of tears.

PMID- 22950294
TI  - Mortal combat.

PMID- 22950295
TI  - Web MDs: Social media are changing how we diagnose disease.

PMID- 22950296
TI  - Payday for payers. Compensation of the top execs at investor-owned insurers
      outpaced that of the leaders at hospitals and specialty care.
AB  - Top executives at investor-owned hospital chains saw their compensation packages
      take a hit last year, amid the debt-ceiling crisis and concerns over how it might
      affect Medicare. Wayne Smith at Community Health Systems led the pack in that
      sector, with a $21 million payday, while Trevor Fetter, left, of Tenet, came in a
      distant second with $10.7 million.

PMID- 22950297
TI  - On the defensive. HCA case highlights fiscal, legal pressures on execs.

PMID- 22950298
TI  - Give and take. Government, states show flexibility on expansion.

PMID- 22950299
TI  - A big heart. Acquisition of practices draws antitrust scrutiny.

PMID- 22950300
TI  - Attacking drug shortages. FTC won't challenge plan to send data to FDA.

PMID- 22950301
TI  - Belt-tightening. New law has Mass. providers 'aggressively focused' on spending.

PMID- 22950302
TI  - Traumatic differences. Study finds variations in costs but not outcomes.

PMID- 22950303
TI  - Reaching for the sky. Work group: meaningful users should aim high, but don't
      have to be perfect.

PMID- 22950304
TI  - Keep executive compensation in check. Ongoing push for transparency and links
      between pay and performance continue to drive trends.

PMID- 22950305
TI  - Finding an apt app. Efforts aim to help navigate mobile health maze.

PMID- 22950306
TI  - Lolo's no choke.

PMID- 22950307
TI  - Survival of the fittest.

PMID- 22950308
TI  - Effects of body weight and season on serum lipid concentrations in sloth bears
      (Melursus ursinus ursinus).
AB  - Serum lipid levels were measured in 66 healthy sloth bears (Melursus ursinus
      ursinus) living under semicaptive conditions with access to natural food
      resources in the Bannerghatta Biological Park (Karnataka, India), a portion of
      their native habitat range in the Indian peninsula. Total cholesterol,
      triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density
      lipoprotein cholesterol levels were analyzed. The effects of age, body weight,
      and season on these lipid parameters were statistically evaluated. There were no
      correlations between age and any of the serum lipid parameters analyzed. Positive
      correlations of body weight to both triglyceride and HDL cholesterol levels in
      these bears were identified. In addition, seasonal trends in physiological serum
      lipid values, potentially due to variations in the sloth bear diet, were
      identified. Serum triglyceride levels were higher during postmonsoon season and
      cholesterol levels were higher during winter compared to other seasons. Serum
      lipid values obtained from sloth bears in this study were also compared to
      previously published data on other members of the family Ursidae. This is the
      first report of serum lipid values as a reference for sloth bears. These values
      can be used as sensitive predictors of overall health and nutritional status to
      aid in the captive management and feeding of these bears.

PMID- 22950309
TI  - Hematological survey of common neotropical bat species from Costa Rica.
AB  - Although bats are one of the largest groups within the class Mammalia and may
      carry several zoonotic diseases, basic information about their hematology is
      limited. In this study, hematocrit (Hct), total white blood cell counts (TWBC;
      leukocytes), and differential white blood cell counts (DWBC) of free-ranging
      Neotropical bats were quantified. Blood samples from 255 bats representing 26
      species from the families of Emballonuridae (3 species; 33 individuals),
      Molossidae (2 species; 26 individuals), Mormoopidae (1 species; 1 individual),
      Phyllostomidae (18 species; 180 individuals), and Vespertilionidae (2 species; 15
      individuals) were collected in a Caribbean lowland rainforest of Costa Rica. Hct
      was measured after centrifugation of microhematocrit capillaries, TWBCs were
      performed using the Unopette system and a hemocytometer, and DWBCs were performed
      on eosin methylene blue stained blood films. Hct of bats ranged between 51.8 +/-
      0.7% for Phyllostomus discolor (n = 27) and 65.8 +/- 2.2% for Molossus sinaloae
      (n = 6). Bat species of the same taxonomic family had comparable TWBCs; these
      were lower for insectivorous emballonurid, molossid, and vespertilionid bat
      species than for mostly phytophagous phyllostomid bat species. However,
      Ectophylla alba (Phyllostomidae) exhibited exceptionally low TWBCs (836 +/- 166
      /microl; n = 10); this was less than half of the TWBCs of all other bat species,
      which ranged from 1,714 +/- 297/microl for Molossus bondae (n = 20) to 7,339 +/-
      1,503/microl for Trachops cirrhosus (n = 6). Species with higher TWBCs tended to
      have lower Hct values. Overall, blood cell morphology was similar to other
      mammalian species. A large number of polychromatophilic erythrocytes and
      differences in lymphocyte morphology were noted. This study provides important
      hematological values for Neotropical bat species and significantly expands the
      knowledge on basal physiological measurements of Chiroptera.

PMID- 22950310
TI  - A study of peripheral blood in hedgehogs in Turkey.
AB  - The aim of this study was to determine diameters of blood cells, differential
      counts of peripheral blood leukocytes, alpha-naphthyl acetate esterase (ANAE),
      acid phosphatase (ACP-ase) activity of some leukocyte types, and enzymatic
      positivity percentages of peripheral blood lymphocytes in two hedgehogs species,
      Hemiechinus auritus, the long-eared hedgehog, and Erinaceus concolor, the
      southern white-breasted hedgehog. Air-dried peripheral blood smears were stained
      with May-Grunwald-Giemsa stain. ANAE and ACP-ase were stained in glutaraldehyde
      acetone-fixed smears. ANAE-positive lymphocytes displayed a dot-like positivity
      pattern characterized with 1-5 reddish brown cytoplasmic granules, whereas ACP
      ase positive lymphocytes displayed a dot-like positivity pattern characterized
      with 1-3 pinkish cytoplasmic granules. Monocytes gave a diffuse and strong
      reaction while neutrophils displayed a weak positive reaction for ANAE and ACP
      ase. No difference was observed in mean diameters of peripheral blood cells of
      these species. It was found that lymphocytes made up the majority (64.3% and
      65.5%) of leukocytes, followed by neutrophils (23.9% and 23.3%), eosinophils
      (9.0% and 7.6%), monocytes (1.8% and 2.3%), and basophils (1.0% and 1.3%) in H.
      auritus and E. concolor, respectively. Mean ANAE positivity oflymphocytes was
      36.6% and 51.3% and ACP-ase positivity was 32.1% and 37.5% for H. auritus and E.
      concolor, respectively. The ANAE positivity of lymphocytes in E. concolor was
      significantly (P < 0.05) higher than that of H. auritus.

PMID- 22950311
TI  - Hepatozoon spp. (Apicomplexa: Hepatozoidae) infection and selected hematological
      values of the neotropical rattlesnake, Crotalus durissus collilineatus (Linnaeus,
      1758) (Serpentes: Viperidae), from Brazil.
AB  - This study aims to establish the hematological values of Crotalus durissus
      collilineatus snakes captured in Brazil as well as to verify the effects of
      hematozoan infection on these snakes. Eighty-three blood samples were drawn from
      C. d. collilineatus specimens for analysis. The sample set was composed of 30
      males and 30 females, recently caught from the wild, and 11 males and 12 females
      bred in captivity. Blood samples were used to determine red blood cell counts,
      white blood cell counts, thrombocyte counts, hematocrit values, hemoglobin
      concentration, and total plasma protein. Blood smears were used to diagnose
      Hepatozoon spp. infection and to calculate the parasitic load in the sample as
      well as the percentage of immature red cells. Results obtained for the wild
      caught animals, with and without parasites, were compared among themselves and
      with the values obtained for the captive-bred animals. Hematological values for
      C. durissus were established. Wild-caught snakes had an infection rate of 38.3%,
      while no Hepatozoon sp. infection was detected in the captive-bred animals. The
      snakes which were not infected by the Hepatozoon sp. exhibited average weight,
      length, and weight-length ratios higher than those of the infected animals. An
      increase in immature red cells was noted in the Hepatozoon-infected snakes.

PMID- 22950312
TI  - Pododermatitis in captive-reared black stilts (Himantopus novaezelandiae).
AB  - A potential cause of pododermatitis ("bumblefoot") was investigated in captive
      reared juvenile black stilts at the Department of Conservation "Kaki Recovery
      Program" at Twizel, New Zealand. To address the importance of substrate, the
      development of clinical signs in individuals was compared among aviaries that
      contained rubber matting and/or salt footbaths, and controls. No effect of either
      experimental manipulation of the environment was apparent on pododermatitis
      development. With the substrate appearing not to be an initiating factor, and a
      previous study that indicated that the birds' diet fulfills the nutritional
      requirements for rearing black stilts in captivity, results of this study suggest
      that insufficient space for exercise may instead be the cause.

PMID- 22950313
TI  - Short-term survival and effects of transmitter implantation into western grebes
      using a modified surgical procedure.
AB  - Two pilot trials and one study in a closely related grebe species suggest that
      Western grebes (Aechmophorus occidentalis) will not tolerate intracoelomic
      transmitter implantation with percutaneous antennae and often die within days of
      surgery. Wild Western grebes (n = 21) were captured to evaluate a modified
      surgical technique. Seven birds were surgically implanted with intracoelomic
      transmitters with percutaneous antennae by using the modified technique
      (transmitter group), 7 received the same surgery without transmitter implantation
      (celiotomy group), and 7 served as controls (only undergoing anesthesia).
      Modifications included laterally offsetting the body wall incision from the skin
      incision, application of absorbable cyanoacrylate tissue glue to the subcutaneous
      space between the body wall and skin incisions, application of a waterproof
      sealant to the skin incision after suture closure, and application of a piece of
      porcine small intestine submucosa to the antenna egress. Survival did not differ
      among the 3 groups with 7 of 7 control, 6 of 7 celiotomy, and 6 of 7 transmitter
      birds surviving the 9-day study. Experimental birds were euthanized at the end of
      the study, and postmortem findings indicated normal healing. Significant
      differences in plasma chemistry or immune function were not detected among the 3
      groups, and only minor differences were detected in red blood cell indices and
      plasma proteins. After surgery, the birds in the transmitter group spent more
      time preening tail feathers than those in the control and celiotomy groups. These
      results demonstrate that, in a captive situation, celiotomy and intracoelomic
      transmitter implantation caused minimal detectable homeostatic disturbance in
      this species and that Western grebes can survive implantation of intracoelomic
      transmitters with percutaneous antennae. It remains to be determined what
      potential this modified surgical procedure has to improve postoperative survival
      of Western grebes that are intracelomically implanted with transmitters with
      percutaneous antennae and released into the wild.

PMID- 22950314
TI  - The effects of a probiotic on blood urea nitrogen and creatinine concentrations
      in large felids.
AB  - Chronic kidney disease is a common finding in older captive exotic felids. The
      purpose of this study was to evaluate the effectiveness of a probiotic to reduce
      blood urea nitrogen and creatinine in large felids. Fifteen adult, large felids
      (6 tigers [Panthera tigris], 5 lions [Panthera leo], 3 cougars [Puma concolor],
      and 1 leopard [Panthera pardus]) were administered a probiotic twice daily after
      a baseline complete blood cell count and plasma chemistry panel was obtained.
      Plasma chemistry values were rechecked at 2 mo (n = 14) and 6 mo (n = 9). There
      was no significant change in blood urea nitrogen over time; however, there was a
      significant change in creatinine over time (P = 0.04). Creatinine concentration
      decreased significantly between 2 and 6 mo (P = 0.02), and a decrease was seen
      between 0 and 6 mo, but this change was not significant (P = 0.05). There was no
      significant difference noted for creatinine concentration between 0 and 2 mo (P =
      0.35). This probiotic may be helpful in large felids with elevated creatinine
      concentrations because of chronic kidney disease; however, further studies are
      warranted.

PMID- 22950315
TI  - Comparison of carfentanil-xylazine and thiafentanil-medetomidine in
      electroejaculation of captive gaur (Bos gaurus).
AB  - Carfentanil citrate and thiafentanil oxalate have been used successfully to
      immobilize captive and free-ranging ungulates. The objective of this study was to
      compare the efficacy and certain physiologic parameters of protocols by using the
      2 opioids in gaur (Bos gaurus). Eight adult gaur bulls were immobilized for
      electroejaculation at Omaha's Henry Doorly Zoo (Omaha, Nebraska, USA). All the
      animals were immobilized twice, by using each of the following protocols one
      time: 10 mg carfentanil combined with 100 mg xylazine (CX), reversed with 1,000
      mg naltrexone and 24 mg yohimbine; and 12 mg thiafentanil combined with 20 mg
      medetomidine (TM), reversed with 120 mg naltrexone and 100 mg atipamezole.
      Immobilization drugs were delivered intramuscularly into the shoulder area via
      pole syringe. Electroejaculation was carried out by a standardized protocol to
      duplicate procedural stimulation on each animal. Induction and recovery times,
      initial rectal temperature, heart rate, respiratory rate, anesthetic depth,
      oxygen saturation, indirect blood pressure, and arterial blood gases were
      recorded at the time of initial handling, before ejaculation, and after
      ejaculation. Antagonists were administered 1/4 i.v. and 3/4 s.q. Both protocols
      require a small volume of drug for a large ungulate, provide smooth induction,
      and adequate anesthesia. Both protocols produced a significant hypoxemia,
      although the animals on CX showed slightly better blood gas values (based on
      lower partial pressure of carbon dioxide) and numerically lower blood pressure
      values. Animals on TM had better muscle relaxation and smoother recoveries, with
      no renarcotization noted. The results of the present study indicate the TM and CX
      protocols used for immobilizing gaur result in similar quality ejaculates that
      can be used for fertility examination as well as for assisted reproduction such
      as artificial insemination. Additional immobilizations need to take place to
      further compare these 2 combinations in this species.

PMID- 22950316
TI  - Comparison of clinical parameters in captive Cracidae fed traditional and
      extruded diets.
AB  - The Cracidae family of neotropical birds is regarded as one of the most severely
      threatened in the world. They traditionally have been extensively hunted, and,
      thus, ex situ efforts for their conservation are recommended and involve the
      optimization of their care in captivity. Nutrition is a fundamental aspect of
      husbandry, which influences survival and reproduction in captivity. In this
      study, a total of 29 animals, including 3 species (Penelope obscura, Penelope
      superciliaris, and Aburria jacutinga), were subjected to monthly physical
      examination and blood sampling before and after dietary conversion from the
      traditional diet of broiler feed, fruits, and vegetables to a nutritionally
      balanced commercial diet specifically designed for wild Galliformes. The diet
      change produced differences in several parameters tested, including an increase
      (P < 0.05) in hemoglobin concentration for all species. Increases (P < 0.05) in
      erythrocyte count, packed cell volume, and body weight were observed in P.
      obscura, with a concomitant decrease in the standard deviation for such
      parameters that show improved uniformity. Globulins and lipase also were reduced
      (P < 0.05) in P. obscura. Although leukocyte count was lowered and eosinophils
      were increased in all 3 species after dietary conversion, only these 2 changes
      were significant (P < 0.05) in P. superciliaris. A. jacutinga had higher (P <
      0.05) blood glucose concentrations than the other species, but diet had no effect
      on this parameter. Blood uric acid concentrations were higher (P < 0.05) after
      conversion to the commercial diet in P superciliaris. The provision of a
      commercial extruded diet as a single food source was beneficial, which led to a
      general improvement in clinical aspects and group uniformity in these 3 species
      of Cracidae.

PMID- 22950317
TI  - Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline
      free acid) in the ball python (Python regius).
AB  - The objective of this study was to determine the pharmacokinetics of a long
      acting formulation of ceftiofur crystalline-free acid (CCFA) following
      intramuscular injection in ball pythons (Python regius). Six adult ball pythons
      received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples
      were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12,
      18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA
      administration. Plasma ceftiofur concentrations were determined by high
      performance liquid chromatography. A noncompartmental pharmacokinetic analysis
      was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95
      microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to
      infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination
      half-life associated with the terminal slope of the concentration-time curve was
      64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr.
      CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory
      concentration (MIC) data for bacterial isolates from snakes are not well
      established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15
      mg/kg) provides adequate plasma concentrations for at least 5 days in the ball
      python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may
      be required.

PMID- 22950318
TI  - Management, breeding, and health records from a captive colony of pekin robins
      (Leiothrix lutea), 2001 - 2010.
AB  - Pekin robins (Leiothrix lutea) were once the most widely kept softbills in
      captivity. As a result of the Convention on the International Trade of Endangered
      Species of Fauna and Flora (CITES-1997), the worldwide trade of wild-caught pekin
      robins has been prohibited due to the depletion of native populations of this
      species. In Brazil, as in other countries, pekin robins imported prior to the
      enactment of the CITES have disappeared from aviaries because the end of the
      birds' natural life span has passed, and only very few captive-bred pekin robins
      now exist. While captive propagation fails to address the primary causes of wild
      bird population decline, it might help the recovery of populations of this
      species. This article presents records made over a 10-yr period of a captive
      colony of pekin robins. Emphasis is placed on the management of the flock, the
      ailments affecting the birds, and the findings associated with bird losses. The
      main causes of bird losses included rearing management failures and age-related
      disorders.

PMID- 22950319
TI  - Diet manipulation as treatment for elevated serum iron parameters in captive
      raggiana bird of paradise (Paradisaea raggiana).
AB  - Elevated serum iron parameters were lowered through dietary manipulation in
      captive Raggiana bird of paradise (Paradisaea raggiana). Study birds were part of
      a captive breeding program consisting of two males and one female, captive born,
      3.5-9 yr of age. Serum iron, total iron binding capacity (TIBC), percentage
      saturation, body weight, albumin, aspartate aminotransferase, and hematocrit were
      monitored at regular intervals for 2.5 yr. Routine diet consisted of a variety of
      fruits, vegetables, a multivitamin supplement, and a commercial low iron avian
      pellet, with a dietary iron content of 55 mg/kg (dry matter basis) or 1.12 mg
      iron/bird/day. Dietary treatment involved removal of the commercial avian pellet
      for 30 days at 6-to 12-mo intervals, resulting in an iron content of 42 mg/kg
      (dry matter basis) or 0.64 mg iron/bird/day. Average serum iron and TIBC were
      decreased by 75% (TIBC) to 80% (serum iron) ofpretreatment values after one 30
      day treatment. Average iron saturation levels were lowered by 10% of pretreatment
      values after one 30-day treatment. Average hematocrit, albumin, aspartate
      aminotransferase, and body weight remained unchanged. No adverse effects were
      noted through the 2.5-yr evaluation period, and breeding behavior was
      undisturbed. Periodic removal of low iron commercial pellets in the diet of
      captive bird of paradise is a safe and effective method for lowering serum iron
      values without need for handling. Periodic application of this technique may be
      useful as a preventive tool to maintain appropriate serum iron values in avian
      species susceptible to iron storage disease.

PMID- 22950320
TI  - Mycobacterium kansasii infection in a bontebok (Damaliscus pygaragus dorcas)
      herd: diagnostic challenges in differentiating from the Mycobacterium
      tuberculosis complex.
AB  - Two adult female bontebok (Damaliscus pygarus dorcas) were euthanized because of
      signs of pneumonia and weakness (case 1), and a nonresponsive lameness with
      draining fistula (case 2). Necropsy findings were similar in both cases and
      consisted of disseminated granulomatous lesions in the liver, kidneys, spleen,
      lungs, pleural surfaces, and multiple lymph nodes. Mycobacterium kansasii was
      isolated from both cases after multiple attempts on a variety of samples by two
      laboratories. The remaining four animals in the herd were tested for antibody
      responses using the Chembio ElephantTB STAT-PAK, DPP VetTB kits, and multi
      antigen print immunoassay (MAPIA), for immune reaction using the intradermal
      tuberculin test, and by tracheal wash cultures, and thoracic radiographs. Banked
      serum samples collected in 2005 and obtained from the original institution,
      revealed 1/9 (11.11%) seropositive animals using the three immunoassays.
      Retesting the current herd in 2008 showed 2/6 (33.33%) seropositive animals by
      the three tests, with MAPIA demonstrating antibody reactivity to MPB83 and MPB70
      proteins. Inconsistent intradermal tuberculin test results, cross-reactivity in
      serologic assays designed for tuberculosis detection, difficulty in obtaining
      definitive identification by culture, and inability to identify a source of
      infection created challenges in distinguishing the atypical mycobacteriosis due
      to M. kansasii from the initially suspected tuberculous infection in this herd.
      Owing to regulatory considerations, differences in host-to-host transmission, and
      source of infection between Mycobacterium tuberculosis complex and nontuberculous
      mycobacteria, correct diagnosis is crucial for management of these diseases in
      wildlife species.

PMID- 22950321
TI  - Nematode and ciliate nasal infection in captive archey's frogs (Leiopelma
      archeyi).
AB  - Archey's frogs (Leiopelma archeyi) are first on the list of evolutionarily
      distinct and globally endangered (EDGE) amphibians. Captive breeding is an
      important strategy for protection of the species, but programs are hampered by a
      lack of information on diseases present in wild and captive populations. Two
      novel nematodes (Koerneria sp. and Rhabditis sp.) were found separately in four
      captive Archey's frogs showing clinical signs of hemorrhagic purulent nasal
      discharge and weight loss. One of these frogs also had a novel protozoal
      infection (Tetrahymena) in the nasal cavity. Koerneria, Rhabditis, and
      Tetrahymena have not previously been reported in amphibians in New Zealand. One
      frog was treated successfully with oral moxidectin at 0.4 mg/kg for the nematode
      infection and topical metronidazole at 10 mg/kg for the protozoal infection. The
      clinical signs abated only after both infections were cleared. The second frog
      died before treatment could be established. The third and fourth frogs were found
      dead.

PMID- 22950322
TI  - Influence of season on the hematological and serum biochemical values of
      bottlenose dolphins (Tursiops truncatus) housed in a controlled environment in
      northern Italy.
AB  - Season appears to influence the physiology of bottlenose dolphins (Tursiops
      truncatus). From 2000 to 2005, blood parameters of three captive bottlenose
      dolphins housed in northern Italy were examined to determine if seasonal
      variation was present. Seasonal variation was observed in the male dolphins, with
      both males exhibiting aminotransferase levels that were higher in autumn and
      lower in winter. Mean serum creatinine levels were higher during summer and lower
      during autumn in the adult male, and mean lactate dehydrogenase higher during
      summer and lower during spring in the juvenile male. Both males exhibited red
      blood cell counts and hemoglobin levels that were higher during autumn and lower
      during summer. This study contributes to the knowledge of baseline hematologic
      and biochemical values based on seasonality in bottlenose dolphins.

PMID- 22950323
TI  - Suspected seminal vesiculitis in an Asian elephant (Elephas maximus).
AB  - A 32-year-old male Asian elephant (Elephas maximus) underwent routine transrectal
      stimulation for semen collection as part of an artificial insemination program.
      The procedure consisted of a preinsemination semen collection followed by two
      consecutive days of semen collections for artificial insemination. The second
      day's sample contained large numbers of inflammatory cells, intracellular
      bacteria, and phagocytized sperm. Semen was submitted for culture and
      sensitivity. Culture revealed Acinetobacter lwoffii, Staphylococcus intermedius,
      Kocuria roseus, and an unidentified gram-positive organism. Empirical antibiotic
      therapy with trimethoprim sulfa was initiated and then changed to enrofloxacin
      based on sensitivity panel results for a total of 28 days of treatment.
      Diagnostic semen collections were performed during treatment and 2 wk
      posttreatment to determine the success of therapy. Posttreatment collections
      revealed resolution of the inflammation. The origin of the infection was
      suspected to be the seminal vesicles.

PMID- 22950324
TI  - Diagnosis and treatment of primary hyperparathyroidism in a bobcat (Lynx rufus).
AB  - An 18-yr-old male bobcat (Lynx rufus) presented with chronic moderate weight loss
      and acute onset of anorexia and lethargy. Hypercalcemia and azotemia were present
      on the serum chemistry panel. Abdominal ultrasound revealed hyperechoic renal
      cortices, but no evidence of neoplasia. Ionized calcium and 25-hydroxyvitamin D
      were mildly elevated, intact parathyroid hormone was severely elevated, and
      parathormone-related protein was undetected, suggesting primary
      hyperparathyroidism with possible renal dysfunction. Azotemia lessened in
      severity following diuresis, but hypercalcemia persisted; thus primary
      hyperparathyroidism was considered the most probable differential diagnosis. A
      second ultrasound including the cervical region revealed a solitary
      intraparenchymal left thyroid nodule. The nodule was surgically excised;
      histopathology confirmed a parathyroid adenoma. Although primary
      hyperparathyroidism was suspected, diagnosis was not achieved from serum
      chemistry values alone. This case emphasizes the importance of diagnostic imaging
      and histopathology in the investigation of persistently abnormal laboratory
      values.

PMID- 22950325
TI  - Evaluation of antibody response to vaccination against West Nile virus in thick
      billed parrots (Rhynchopsitta pachyrhyncha).
AB  - West Nile virus (WNV) was first documented in North America in New York City in
      1999. Several deaths attributable to WNV have been reported in captive thick
      billed parrots (Rhynchopsitta pachyrhyncha), an endangered psittacine native to
      North America. The serologic responses in 12 captive adult thick-billed parrots
      after a series of three initial WNV vaccine injections with annual boosters over
      6 yr was evaluated. In addition, the serologic responses of 11 thick-billed
      parrot chicks following an initial vaccination series to determine if there were
      seroconversions were also reported. Most adults (67%) had seroconverted after 5
      yr of annual vaccination, with a median titer of 1:80 (range 1:40-1:160) for
      those that seroconverted. After the first year, birds were likely naturally
      exposed to WNV, which limited interpretation of titers. None of the chicks
      seroconverted during the initial three-vaccine series; only two of four chicks
      (50%) had seroconverted when tested at the 1-yr yearly booster, and at 2 yr,
      three of four chicks had seroconverted. Although some birds had detectable
      antibody titers, it is unclear whether this vaccine can reliably provide
      protection against WNV in thick-billed parrots.

PMID- 22950326
TI  - Minimum anesthetic concentration and cardiovascular dose-response relationship of
      isoflurane in cinereous vultures (Aegypius monachus).
AB  - This study aimed to determine the minimum anesthetic concentration (MAC) and dose
      related cardiovascular effects of isoflurane during controlled ventilation in
      cinereous vultures (Aegypius monachus). The MAC was determined for 10 cinereous
      vultures as the midpoint between the end-tidal isoflurane concentration that
      allows gross purposeful movement and that which prevents the movement in response
      to clamping a pedal digit. Immediately after the MAC was determined, the
      cardiovascular effects of isoflurane at 1.0, 1.5, and 2.0 times the MAC were
      investigated in seven of the 10 birds. The MAC of isoflurane for 10 cinereous
      vultures during controlled ventilation was 1.06 +/- 0.07% (mean +/- SD). When the
      isoflurane concentration was increased to 1.5 and 2.0 times the MAC, there was
      significant dose-dependent decrease in the arterial blood pressure. However, the
      heart rate did not change over a range of 1.0 to 2.0 times the MAC.

PMID- 22950327
TI  - Cuterebrid myiasis (Diptera: Oestridae) in captive ring-tailed lemurs (Lemur
      catta) at a South Carolina zoo.
AB  - In September 2008, two ring-tailed lemurs (Lemur catta), comprising a mother
      daughter pair, at the Greenville Zoo, Greenville, South Carolina, USA, were
      diagnosed with cuterebrid myiasis (Diptera: Oestridae) subsequent to sudden death
      of the adult lemur. On necropsy, a single bot warble was discovered in the
      subcutis of the axillary region. Histopathology revealed a severe eosinophilic
      bronchopneumonia. The juvenile lemur was inspected and found to have warbles on
      three separate dates in late September. One representative bot fly larva was
      identified as a Cuterebra sp. that normally infests lagomorphs in the
      southeastern United States. Cuterebrid myiasis is rarely reported in lemurs and
      has not been previously associated with pneumonia or death in these animals.

PMID- 22950328
TI  - Recovery of Arcobacter spp. from nonlivestock species.
AB  - The genus Arcobacter encompasses campylobacter-like organisms that grow in air at
      25 degrees C. Arcobacter has been detected or isolated from clinically healthy
      livestock as well as aborted fetuses and has been presumptively identified as
      either Campylobacter or Leptospira, based on its growth in selective semisolid
      media. Because reports from nonlivestock species are limited, this study examined
      nine presumptive isolates of Arcobacter spp. from an alpaca (Vicugna pacos),
      black rhinoceros (Diceros bicornis), white rhinoceros (Ceratotherium simum),
      gorilla (Troglodytes gorilla), gazelle (Eudorcas thomsoni), rhea (Rhea
      americana), and aborted equine fetuses. Seven of these nine phenotypically
      identified isolates of Arcobacter were confirmed by a multiplex polymerase chain
      reaction assay. The remaining two isolates were subsequently identified as
      Arcobacter skirrowii (Case 5) and Campylobacter jejuni (Case 6) by sequence
      analysis of a 527-base pair fragment of the 16S rRNA gene. Together, these cases
      underscore the challenges to a clinical laboratory of identifying Arcobacter in
      cases which mimic vibrionic abortion or leptospirosis.

PMID- 22950329
TI  - Diaphragmatic hernia in a two-year-old alpaca (Vicugna pacos).
AB  - A 2-yr-old male intact alpaca (Vicugna pacos) was admitted for a 4-day history of
      anorexia and colic. Five months prior, the alpaca had undergone surgical removal
      of a duodenal trichophytobezoar and had recovered uneventfully. The alpaca died
      under anesthesia, and diaphragmatic herniation of the third gastric compartment
      (C3) was diagnosed at necropsy. A defect was identified in the left dorsal
      hemidiaphragm accompanied by herniation of 80% of C3 and the aboral portion of
      the second gastric compartment into the pericardial sac. The smooth margins and
      dorsal location of the diaphragmatic defect suggested a congenital origin.
      Diaphragmatic herniation is uncommon in camelids, and only one other case has
      been reported. Due to the dorsal location of the diaphragmatic defect in this
      animal, positioning during the previous surgery may have initiated a partial
      entrapment of gastric compartments, leading to a more complete incarceration
      between when the animal was discharged and presented again.

PMID- 22950330
TI  - Hematochezia in an African spurred tortoise (Centrochelys sulcata).
AB  - An African spurred tortoise (Centrochelys sulcata) that had been housed with a
      conspecific was presented for tenesmus, diarrhea, and hematochezia of 48 hr
      duration. Husbandry was considered substandard. Hematology and plasma biochemical
      analysis revealed dehydration. Urinalysis was considered normal and fecal
      examination was negative for parasitic ova and protozoa. Radiography demonstrated
      moderate constipation. Initial treatment consisted of fluid therapy,
      enrofloxacin, metoclopramide, and improvement of husbandry practices. Recurrence
      of hematochezia developed 2 wk after initial presentation. Cloacoscopy followed
      by manual exteriorization of the penis revealed a puncture wound on the dorsal
      surface of the corpus cavernosum proximal to the glans penis. The wound was
      sutured using an absorbable monofilament material. The tortoise recovered
      uneventfully and was asymptomatic for the following 6 mo.

PMID- 22950331
TI  - Pheochromocytoma in a white rhinoceros (Ceratotherium simum).
AB  - A 46-yr-old male white rhinoceros (Ceratotherium simum) died during anesthesia
      following agonal excitation. On postmortem, a well-demarcated 2.5-cm tan mass was
      identified in the right adrenal gland. Histopathology confirmed the presence of a
      pheochromocytoma, and elevated levels of epinephrine in serum collected shortly
      prior to the animal's death, as compared with sera from healthy controls,
      demonstrated the functional nature of the tumor. Although rare, pheochromocytoma
      should be considered as a differential diagnosis in cases of suspected
      hypertension and acute death in rhinos.

PMID- 22950332
TI  - Clinical challenge. Radio-dense foreign bodies.

PMID- 22950333
TI  - [Cancer and the family].

PMID- 22950334
TI  - [Reactive changes in psychological condition and behaviour in children of parents
      with cancer--results of an epidemiological survey].
AB  - Children of cancer patients are at risk for developing psychological symptoms.
      The parental appraisal of the child's psychological condition is a key variable
      for the utilization of child-centred psychosocial services. This study aimed at
      the systematic analysis of parental appraisals of changes in the emotional
      condition or behaviour of their children. We conducted an epidemiologic survey
      with a sample size of 1,809 patients with different cancer diagnoses, giving
      information about 2,581 children aged 21 years or younger at time of diagnosis.
      Quantitative information on children's distress during the disease and on changes
      in psychological condition or behaviour and qualitative information on the kind
      of changes were analysed. About half of the children were considered to be
      psychologically strongly affected during the disease. For about 25 % negative
      changes in psychological condition or behaviour are reported, positive changes
      are reported for 20 % of the children. Negative changes are most frequently
      described in young children (up to five years), positive changes are most
      frequently described in young adults (18 to 21 years). The results indicate that
      from the cancer parent's view many children are substantially distressed. Thus,
      the implementation of additional preventive psychosocial services seems
      reasonable and necessary.

PMID- 22950335
TI  - [Support for families with a parent diagnosed with cancer and children under the
      age of five--delineation of a counselling concept].
AB  - Parents of infants and young children, who have been diagnosed with cancer wish
      to protect their child from the emotional strains of their illness. They wonder,
      what the child can understand about the illness and how it is able to process or
      assimilate the experience of the illness. In fact, infants and young children are
      particularly sensitive to the degree of emotional burden and the mental state of
      their parents and will experience varying degrees of insecurity due to even small
      changes in their relationship with their parents. On the basis of psychological
      development parameters specific to this age group as well as scientific findings
      on risk and protection factors an integrated interaction based counseling
      approach was developed. Within this approach, support for the communication
      between parent and child in view of the specific strains of their illness, both
      non-verbal and in the child's early stages of verbal communication, is central.
      In the present article the counselling concept is described and illustrated by
      case studies. Application and limits are discussed.

PMID- 22950336
TI  - [Anticipatory grief in adolescents and young adults coping with parental cancer].
AB  - By the current state of research, it cannot be answered clearly how adolescents
      experience anticipatory grief and if and to which extent this process differs
      from anticipatory grief of adults. The present study will fill this gap by
      providing both a quantitative and a qualitative description of anticipatory grief
      processes. Therefore, 74 adolescents and young adults (11-21 years), whose
      parents have suffered from cancer, completed an adapted version of the
      "Trauerfragebogen" (Weiser u. Ochsmann, 2002). Additionally a subsample of n = 38
      took part in a qualitative guided interview. Based on these interviews, 16
      categories were formed, that were assigned to two types of stressors. Beside
      communication and prioritization of family, different symptoms of grief were the
      central category in the loss-oriented type, where fears of loss, compassion and
      concern were of crucial importance. Also categories of the restoration-oriented
      type were strongly present. Thus, it seems that young people generally manage to
      accept their new role in the stressful family situation and they have a series of
      coping mechanisms available to do so. This was also reflected in the quantitative
      data, were the subscale "Inner Strength" reached the highest value. In the
      counselling of adolescents with cancer-diseased parents, both loss-oriented and
      restoration-oriented processes should equally be recognized and encouraged.

PMID- 22950337
TI  - [Depression in children of cancer patients over time and dependence of the
      parental distress].
AB  - This study was part of the German multicentre project "Psychosocial Services for
      Children of Parents with Cancer" (2009-2012, research grant: German Cancer Aid).
      60 parent-child-dyads (children's age: >10 years, at least one parent with
      cancer) could be included in data analysis. Depressive symptoms of children were
      assessed with the CES-DC at two times (t1 and t2). Depression scores were
      compared with a representative comparison group from the general population.
      Further, the relationship between the distress of cancer patients and the
      depression of the children was examined. Children with at least one parent with
      cancer were significantly more depressed than the comparison group (t1 and t2).
      25.8% of the boys and 35.7% of the girls reported clinically relevant scores of
      depression at t1. There were no significant changes in the depression scores on
      the individual level for boys and girls at t2. There was a positive correlation
      between children's depression (t1) and the parental anxiety at t1 with r = 0.26
      (p <0.05). Depressive symptoms in children of parents with cancer persist over
      time, and therefore should be identified early.

PMID- 22950338
TI  - [Parental cancer--parents ways of coping, family functioning, and psychosocial
      adjustment of dependent children].
AB  - Children exposed to parental cancer have an increased risk of mental health
      problems. However, the parental illness itself and its features do not predict
      children's psychological adjustment. Parent- and family-related factors are more
      predictive for children's well-being and the incidence of psychopathological
      symptoms, respectively. This study focuses on parental ways of coping with
      illness from both, the ill and healthy parent's perspective, and the relationship
      with family functioning and children's adjustment. Results show a significant
      impact of parental coping styles on children's health-related quality of life and
      psychopathological symptoms and, furthermore, that this relationship is mediated
      by aspects of family functioning. This study support the importance of family
      systems approaches. Implications for further studies and practical issues are
      discussed.

PMID- 22950339
TI  - Proposed amendments to the Clinical Laboratory Improvement Amendments of 1988 and
      the Health Insurance Portability and Accountability Act of 1996: opening doors to
      patient access or to increased liability for health care professionals?

PMID- 22950340
TI  - Highly sensitive troponin immunoassays: navigating between the scylla and
      charybdis.
AB  - The recent development and introduction into clinical and laboratory practice of
      the novel highly sensitive cardiac troponin assays has contributed to improve the
      diagnosis and risk stratification of patients presenting with suspected
      myocardial injury and acute coronary syndrome at the emergency department (ED).
      The enhanced ability to detect very low amount of troponin in blood with the
      novel tests has also raised the challenge of intercepting values above the 99th
      percentile of the reference population in apparently healthy subjects as well as
      several patients with comorbidities different from myocardial infarction. As
      such, the diagnostic approach and the triage of chest pain patients need to be
      readjusted and, most probably, the role of clinical judgment will assume greater
      importance than with the old generation immunoassays. In this perspective, a
      strategy based on the "delta biomarker approach" rather than that based on the
      traditional "peak" value might be more viable, since the observation of a dynamic
      pattern of troponin values might help discriminating the timing of injury as well
      as distinguishing acute from chronic etiologies and thereby increasing both the
      specificity and the positive predictive value (PPV) of the test. Nevertheless,
      this approach would require an accurate definition of the reference ranges as
      well as the identification of the magnitude of increase or decrease during serial
      sampling. We are thereby navigating between the Scylla (i.e., definition of
      appropriate 99th percentile of the reference population) and Charybdis (i.e.,
      identification of a reliable delta threshold) of the novel highly sensitive
      immunoassays. The aim of this article is to provide an overview on the clinical
      impact of the highly sensitive cardiac troponin immunoassays in the differential
      diagnosis of patients presenting to ED with thoracic pain suggestive for acute
      coronary syndrome.

PMID- 22950341
TI  - Circulating forms of the b-type natriuretic peptide prohormone: pathophysiologic
      and clinical considerations.
AB  - Recent studies reported that many different biochemical forms of B-type-related
      peptides circulate in human blood. In particular, a significant amount of the
      prohormone peptide (i.e., proBNP108) can be detected in plasma of patients with
      heart failure. These data indicate that the posttranslational maturation
      processing of the B-type natriuretic peptide (BNP) precursor may not be efficient
      in heart failure. The aim of this chapter is to describe the biochemical pathways
      of proBNP108 maturation and to discuss the pathophysiological relevance of
      alteration of the posttranslational maturation mechanisms in heart failure. An
      impaired cardiac endocrine function was proposed to explain the altered
      electrolyte and fluid homeostasis occurring in chronic heart failure. Recent
      studies demonstrated that a great part of BNPs assayed by immunoassay methods in
      healthy subjects and in patients with cardiovascular disease is devoid of
      biological activity. These findings suggest that an alteration in
      posttranslational maturation of BNP precursor may promote the resistance to
      biological action of BNP in patients with heart failure at a prereceptor level.
      These studies also open a new and more complex scenario regarding the circulating
      BNPs. The active hormone (i.e., BNP1-32) may be produced even in vivo from the
      circulating precursor proBNP108 by plasma enzyme degradation, such as the soluble
      form of corin, possibly able to process the circulating intact precursor of
      natriuretic hormones. As a future perspective, the simultaneous measurement of
      the proBNP1-108 and the active peptide BNP1-32 with more specific methods could
      allow a more accurate estimation of both production/secretion of B-type-related
      peptides from cardiomyocytes and the true activity of the cardiac endocrine
      function.

PMID- 22950342
TI  - Next generation natriuretic peptide measurement.
AB  - Plasma measurement of natriuretic peptides is a "must" for clinical laboratories.
      For the next generation measurement, the unraveling of the molecular complexity
      of the peptides points toward a more qualitative assessment, as the
      posttranslational processing also changes with disease. Changes in the molecular
      heterogeneity could in itself contain valuable information of clinical status,
      and the time seems right for industry and dedicated researchers in the field to
      get together and discuss the next generation natriuretic peptide measurement. In
      such an environment, new strategies can be developed with the mutual aim of
      making already very good plasma markers even better.

PMID- 22950343
TI  - Cytokines in muscle damage.
AB  - Multiple cellular and molecular processes are rapidly activated following
      skeletal muscle damage to restore normal muscle structure and function. These
      processes typically involve an inflammatory response and potentially the
      consequent occurrence of secondary damage before their resolution and the
      completion of muscle repair or regeneration. The overall outcome of the
      inflammatory process is potentially divergent, with the induction of prolonged
      inflammation and further muscle damage, or its active termination and the
      promotion of muscle repair and regeneration. The final, detrimental, or
      beneficial effect of the inflammatory response on muscle repair is influenced by
      specific interactions between inflammatory and muscle cell-derived cytokines that
      act as positive and/or negative regulators to coordinate local and systemic
      inflammatory-related events and modulate muscle repair process. A crucial balance
      between proinflammatory and anti-inflammatory cytokines appears to attenuate an
      excessive inflammatory reaction, prevent the development of muscle fibrosis, and
      adequately promote the regenerative process. In this review, we address the
      interactive cytokine responses following muscle damage, in the context of
      induction and progression, or resolution of muscle inflammation and the promotion
      of muscle repair.

PMID- 22950344
TI  - The immune system--a hidden treasure for biomarker discovery in cutaneous
      melanoma.
AB  - This chapter describes how skin immune system (SIS) is specifically involved in
      the development of cutaneous melanoma. Local immune surveillance is presented as
      a complex process that comprises markers to be monitored in disease's evolution
      and in therapy. The ranking of tissue or soluble immune markers in a future panel
      of diagnostic/prognostic panel are evaluated. Taking into account the
      difficulties of cutaneous melanoma patients' management, this chapter shows the
      immune surveillance at the skin level, the conditions that favor the tumor escape
      from the immunological arm, the immune pattern of skin melanoma with
      diagnostic/prognostic relevance, the circulatory immune markers, and, last but
      not least, how immune markers are used in immune-therapy monitoring. The chapter
      cannot be exhaustive but will give the reader a glimpse of the complex immune
      network that lies within tumor escape and where to search for immune
      therapeutical targets in skin melanoma.

PMID- 22950345
TI  - Neutrophil gelatinase-associated lipocalin in acute kidney injury.
AB  - Acute kidney injury (AKI) is recognized as an independent risk factor for
      morbidity and mortality. Unfortunately, this syndrome was historically
      underdiagnosed due to inconsistent definition of AKI as well as insensitive and
      nonspecific diagnostic tools. Recent advances in defining AKI, understanding its
      pathophysiology, and improving its diagnostic accuracy have an impact in disease
      management and clinical outcome. Prompt recognition and treatment of AKI still
      remains the cornerstone of clinical management of this syndrome. This chapter
      focuses on the recent advances in diagnosis of AKI using novel serum and urine
      biomarkers. The role of neutrophil gelatinase-associated lipocalin (NGAL) in
      pathophysiology and diagnosis of AKI is presented. A detailed analysis of the
      biology of NGAL and presentation of laboratory methods of measurement is also
      provided. The role of NGAL as biomarker beyond the boundaries of nephrology is
      also presented.

PMID- 22950346
TI  - Urinary metabolomics in newborns and infants.
AB  - Metabolomics is a new approach based on the systematic study of the full
      complement of metabolites in a biological sample. This technology consists of two
      sequential steps: (1) an experimental technique, based on nuclear magnetic
      resonance (NMR) spectroscopy or mass spectrometry, designed to profile low
      molecular-weight compounds, and (2) multivariate data analysis. The metabolomic
      analysis of biofluids or tissues has been successfully used in the fields of
      physiology, diagnostics, functional genomics, pharmacology, toxicology, and
      nutrition. Recent studies have evaluated how physiological variables or
      pathological conditions can affect metabolomic profiles of different biofluids in
      pediatric populations. The overall metabolic status of the neonate is little
      known. If more information on perinatal/neonatal maturational processes and their
      metabolic background were available, the management of sick or preterm newborns
      might be improved. Currently, the use of metabolomics in neonatology is still in
      the pioneering phase. Meaningful diagnostic information and simple, noninvasive
      collection techniques make urine a particularly suitable biofluid for metabolomic
      approach in neonatal medicine, although blood has also been investigated.
      Different fields of neonatology such as postnatal maturation, asphyxia/hypoxia,
      inborn errors of metabolism, nutrition, nephrouropathies, nephrotoxicity,
      cardiovascular diseases, and other conditions have been investigated using a
      metabolomic approach. Together with genomics and proteomics, metabolomics appears
      to be a promising tool in neonatology for the monitoring of postnatal metabolic
      maturation, the identification of biomarkers as early predictors of outcome, the
      diagnosis and monitoring of various diseases, and the "tailored" management of
      neonatal disorders.

PMID- 22950347
TI  - Antihypertensive role of polyphenols.
AB  - Hypertension is considered the most important risk factor in the development of
      cardiovascular disease. Considerable evidence suggests that oxidative stress,
      which results in an excessive generation of reactive oxygen species (ROS), plays
      a key role in the pathogenesis of hypertension. This phenomenon leads to
      endothelial dysfunction, an imbalance between endothelium-derived relaxing
      factors, such as nitric oxide (NO), and contracting factors, such as angiotensin
      II and endothelin (ET)-1, favoring the latter. Vascular remodeling also takes
      place; both processes lead to hypertension establishment. Antioxidant therapies
      have been evaluated in order to decrease ROS production or increase their
      scavenging. In this line, polyphenols, widespread antioxidants in fruits,
      vegetables, and wine, have demonstrated their beneficial role in prevention and
      therapy of hypertension, by acting as free radical scavengers, metal chelators,
      and in enzyme modulation and expression. Polyphenols activate and enhance
      endothelial nitric oxide synthase (eNOS) expression by several signaling
      pathways, increase glutathione (GSH), and inhibit ROS-producing enzymes such as
      NADPH and xanthine oxidases. These pathways lead to improved endothelial
      function, subsequent normalization of vascular tone, and an overall
      antihypertensive effect. In practice, diets as Mediterranean and the "French
      paradox" phenomenon, the light and moderate red wine consumption, supplementation
      with polyphenols as resveratrol or quercetin, and also experimental and clinical
      trials applying the mentioned have coincided in the antihypertensive effect of
      polyphenols, either in prevention or in therapy. However, further trials are yet
      needed to fully assess the molecular mechanisms of action and the appearance of
      adverse reactions, if a more extensive recommendation of polyphenol introduction
      in diet wants to be made.

PMID- 22950348
TI  - Personal growth and the transition to grandfatherhood.
AB  - The study examined personal growth among new grandfathers (n = 101, age 45-67), 2
      to 24 months after the birth of their first grandchild. Specifically, it
      investigated the contribution of internal resources (self-esteem), perceived
      characteristics of the situation (grandparenthood distress and cognitive
      appraisals of threat, challenge, and self-efficacy), and external resources
      (perceived marital relationship) to the experience of growth. Associations with
      several background variables, including age, education, health and economic
      status, grandchild's age, and frequency of grandfather-grandchild meetings, were
      also examined. The results showed that lower internal resources, a positive
      assessment of the situation, and lower education were most closely associated
      with a higher experience of growth in first-time grandfathers. The discussion
      relates to the uniqueness of focusing on grandfathers and the potential for
      personal growth in this new family role.

PMID- 22950349
TI  - Effects of aging and education on false memory.
AB  - This study examined the effects of aging and education on participants' false
      memory for words that were not presented. Three age groups of participants with
      either a high or low education level were asked to study lists of semantically
      related words. Both age and education were found to affect veridical and false
      memory, as indicated in the recall and recognition of the studied word and
      nonstudied lures. A low education level had a negative effect on memory
      performance for both young and middle-aged adults. Older adults with a high level
      of education had a higher level of false memory than those with a lower education
      level. The results of this study are discussed in terms of the importance of
      education on false memory and mechanisms that create false memory of words in
      older adults.

PMID- 22950350
TI  - Daily social exchanges and affect in middle and later adulthood: the impact of
      loneliness and age.
AB  - Although daily social exchanges are important for well-being, it is unclear how
      different types of exchanges affect daily well-being, as well as which factors
      influence the way in which individuals react to their daily social encounters.
      The present study included a sample of 705 adults aged 31 to 91, and using
      Multilevel Modeling analyses investigated whether loneliness or age moderate the
      relationship between daily affect and daily social exchanges with family and
      friends. Results indicated differences between events involving family and those
      involving friends. Furthermore, lonelier individuals benefitted more from
      positive events than less lonely adults but were not more negatively reactive to
      negative events. Moreover, results suggested that older adults' affect is more
      independent of both positive and negative social events compared to younger
      people. Implications are discussed for the importance of daily social exchanges,
      daily social stress vulnerability, and the influences of loneliness across middle
      and later adulthood.

PMID- 22950351
TI  - The application of a generativity model for older adults.
AB  - Generativity is a concept first introduced by Erik Erikson as a part of his
      psychosocial theory which outlines eight stages of development in the human life.
      Generativity versus stagnation is the main developmental concern of middle
      adulthood; however, generativity is also recognized as an important theme in the
      lives of older adults. Building on the work of Erikson, McAdams and de St. Aubin
      (1992) developed a model explaining the generative process. The aims of this
      article are: (a) to explore the relationship between generativity and older
      adults as it appears in research literature; and (b) to examine McAdam's model
      and use it to explain the role of generativity in older adults who share life
      stories with gerontology students through an oral history project.

PMID- 22950352
TI  - A gated-7T MRI technique for tracking lung tumor development and progression in
      mice after exposure to low doses of ionizing radiation.
AB  - A gated-7T magnetic resonance imaging (MRI) application is described that can
      accurately and efficiently measure the size of in vivo mouse lung tumors from
      ~0.1 mm(3) to >4 mm(3). This MRI approach fills a void in radiation research
      because the technique can be used to noninvasively measure the growth rate of
      lung tumors in large numbers of mice that have been irradiated with low doses
      (<50 mGy) without the additional radiation exposure associated with planar X ray,
      CT or PET imaging. High quality, high resolution, reproducible images of the
      mouse thorax were obtained in ~20 min using: (1) a Bruker 7T micro-MRI scanner
      equipped with a 60 mm inner diameter gradient insert capable of generating a
      maximum gradient of 1000 mT/m; (2) a 35 mm inner diameter quadrature
      radiofrequency volume coil; and (3) an electrocardiogram and respiratory gated
      Fast Low Angle Shot (FLASH) pulse sequence. The images had an in-plane image
      resolution of 98 MUm and a 0.5 mm slice thickness. Tumor diameter measured by MRI
      was highly correlated (R(2) = 0.97) with the tumor diameter measured by
      electronic calipers. Data generated with an initiation/promotion mouse model of
      lung carcinogenesis and this MRI technique demonstrated that mice exposed to 4
      weekly fractions of 10, 30 or 50 mGy of CT radiation had the same lung tumor
      growth rate as that measured in sham-irradiated mice. In summary, this high
      field, double-gated MRI approach is an efficient way of quantitatively tracking
      lung tumor development and progression after exposure to low doses of ionizing
      radiation.

PMID- 22950353
TI  - Collagen-templated bioactive titanium dioxide porous networks for drug delivery.
AB  - A Type I collagen gel was used as a template for fabricating porous titanium
      dioxide networks. Conducting sol-gel chemistry within the template, followed by a
      mild solvothermal treatment (selected TiO(2)-collagen hybrids only), and then
      calcination to remove the template, produced anatase TiO(2) porous networks
      composed of mesoporous fibers. The collagen morphology was retained. TiO(2)
      fibers had walls up to 300 nm in thickness and hollow cores where the template
      was removed. Crystallite size, specific surface area (12.3-110 m(2) g(-1)),
      mesopore diameter (4.2-8.8 nm), and pore volume of the networks varied under
      different synthesis conditions; solvothermal treatment of the hybrid doubled the
      surface area and mesopore diameter of the final material. Biomineralization was
      studied by immersion in a simulated body fluid. All networks displayed in vitro
      bioactivity, and hence potential bone-bonding capability, with apatite clusters
      growing on the fibers. Drug delivery was assessed by the adsorption and release
      of anti-inflammatory ibuprofen. Ibuprofen was stored both at the fiber surface
      and in mesopores below 15 nm in diameter, while release was a sustained diffusion
      process. The network solvothermally treated as a hybrid adsorbed ibuprofen up to
      58.9 mg g(-1). The TiO(2) networks compared favorably with literature drug
      delivery vehicles when ibuprofen loading was normalized against surface area.
      Therefore, porous TiO(2) networks have potential as materials for biomedical
      applications.

PMID- 22950354
TI  - One-pot synthesis of benzo[1,4]thiazin-3(4H)-ones and a Theoretical Study of the
      S-N type Smiles rearrangement mechanism.
AB  - Benzo[1,4]thiazin-3(4H)-one derivatives are conveniently prepared in one pot via
      a Smiles rearrangement (SR) tandem reaction. In order to understand the reaction,
      we present here a theoretical study on the S-N type SR mechanism.

PMID- 22950355
TI  - Photoswitchable metal coordinating tweezers operated by light-harvesting
      dendrimers.
AB  - A dendrimer bearing two cyclam units linked by an azobenzene moiety, and
      luminescent naphthalene units at the periphery performs three different functions
      (light-harvesting, photoisomerization and coordination of metal ions) which can
      cooperate or interfere depending on the nature of the metal ion. It is thus an
      example of light controlled molecular tweezers in which Zn(II) coordination
      allows 100% efficient photosensitization of azobenzene switching, while Cu(II)
      shuts down azobenzene isomerization.

PMID- 22950356
TI  - Branched polymeric media: perchlorate-selective resins from hyperbranched
      polyethyleneimine.
AB  - Perchlorate (ClO(4)(-)) is a persistent contaminant found in drinking groundwater
      sources in the United States. Ion exchange (IX) with selective and disposable
      resins based on cross-linked styrene divinylbenzene (STY-DVB) beads is currently
      the most commonly utilized process for removing low concentrations of ClO(4)(-)
      (10-100 ppb) from contaminated drinking water sources. However, due to the low
      exchange capacity of perchlorate-selective STY-DVB resins (~0.5-0.8 eq/L), the
      overall cost becomes prohibitive when treating groundwater with higher
      concentration of ClO(4)(-) (e.g., 100-1000 ppb). In this article, we describe a
      new perchlorate-selective resin with high exchange capacity. This new resin was
      prepared by alkylation of branched polyethyleneimine (PEI) beads obtained from an
      inverse suspension polymerization process. Batch and column studies show that our
      new PEI resin with mixed hexyl/ethyl quaternary ammonium chloride exchange sites
      can selectively extract trace amounts of ClO(4)(-) from a makeup groundwater (to
      below detection limit) in the presence of competing ions. In addition, this resin
      has a strong-base exchange capacity of 1.4 eq/L, which is 1.75-2.33 times larger
      than those of commercial perchlorate-selective STY-DVB resins. The overall
      results of our studies suggest that branched PEI beads provide versatile and
      promising building blocks for the preparation of perchlorate-selective resins
      with high exchange capacity.

PMID- 22950357
TI  - Effect of cardinal directions on gall morphology and parasitization of the gall
      wasp, Cynips quercusfolii.
AB  - This survey investigated the relationship between gall morphology and some
      fitness components in the asexual generation of Cynips quercusfolii L.
      (Hymenoptera: Cynipidae). Results showed that larger C. quercusfolii galls were
      formed on the south side of oak trees Quercus infectoria Olivier (Fagales:
      Fagaceae). Larval chamber diameter in the gall was similar, but gall diameter and
      gall wall thickness varied with the location of the gall on the tree. Cynips
      quercusfolii was attacked by parasitoids, and the south-facing galls suffered
      significantly lower parasitoid attacks. Thickness of gall walls and parasitism
      rate were negatively correlated. Mean gall diameter and gall wall thickness were
      significantly larger in south-facing galls than other directions, but the
      difference in the mean larval chamber diameter was not significant. These results
      suggest that the position of galls on the tree affected gall wall thickness, and
      this plays an important role in parasitoid attacks. These results suggest that C.
      quercusfolii prefer to attack the south side of oak trees, and selection of this
      side by wasps led to formation of larger galls with thick walls that decreased
      parasite attack, which will affect growth and survival of wasp larvae.

PMID- 22950358
TI  - Natalizumab treatment during pregnancy - effects on the neonatal immune system.
AB  - BACKGROUND: Pregnancies in women with severe relapsing-remitting multiple
      sclerosis treated with natalizumab constitute a major challenge, because
      withdrawal of the drug may cause relapses but continuation might have unknown
      effects on the infantile immune system. AIMS OF THE STUDY: To identify the impact
      of maternal natalizumab treatment during pregnancy on basic immune functions of
      the newborn. METHODS: Basic immunological testing and assessment of the
      chemotaxis rate of freshly isolated T lymphocytes in the presence and absence of
      CXCL12 was performed in two neonates, whose mothers were treated with natalizumab
      until the 34th week of pregnancy (pw). RESULTS: Both children had an uneventful
      birth. However, a reduction in the CXCL12-induced T-cell chemotaxis was found in
      both children. In contrast, the chemotaxis rate of unstimulated T lymphocytes was
      not altered. The distribution of the lymphocyte subpopulations was investigated
      only in case 1 and was normal. CONCLUSIONS: Here, we present to our knowledge the
      first assessment of T lymphocytes chemotaxis rate in two natalizumab-exposed
      newborns. A significant reduction in the CXCL12-induced chemotaxis rate of T
      lymphocytes has been observed and may compromise host defence function in early
      life. More clinical and immunological data on natalizumab-exposed neonates are
      warranted.

PMID- 22950359
TI  - Photodegradation of ormetoprim in aquaculture and stream-derived dissolved
      organic matter.
AB  - Ormetoprim (OMP) is an antibiotic approved for use in the United States to
      prevent the spread of disease in freshwater aquaculture. It has been shown in the
      previous literature to be photochemically stable to direct photolysis, but the
      role of photosensitization processes in the presence of dissolved organic matter
      (DOM) on the rate of degradation is not well understood. The present results show
      that water and DOM (specifically the fulvic acid fraction) isolated from a
      eutrophic aquaculture catfish pond and a nearby stream (Deer Creek) at the
      Mississippi State University Delta Research and Extension Center facility in
      Stoneville, MS, significantly increased the phototransformation of OMP relative
      to direct photolysis. Similar results were reported for reference fulvic acids
      obtained from the International Humic Substances Society. Results from a
      combination of scavenging experiments and experiments conducted under anoxic
      conditions indicate the indirect photodegradation pathway occurs by hydroxyl
      radical, singlet oxygen attack, and reaction with triplet excited-state DOM.

PMID- 22950360
TI  - Ambulatory ECG-based T-wave alternans and heart rate turbulence can predict
      cardiac mortality in patients with myocardial infarction with or without diabetes
      mellitus.
AB  - BACKGROUND: Many patients who survive a myocardial infarction (MI) remain at risk
      of sudden cardiac death despite revascularization and optimal medical treatment.
      We used the modified moving average (MMA) method to assess the utility of T-wave
      alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients
      with or without diabetes mellitus (DM). METHODS: We prospectively enrolled 248
      consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM
      patients); 75 controls without cardiovascular disease (group control). Both TWA
      and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed
      by two parameters ? turbulence onset (TO) and turbulence slope (TS). HRT was
      considered positive when both TO >=0% and TS <=2.5 ms/R-R interval were met. The
      endpoint was cardiac mortality. RESULTS: TWA values differed significantly
      between MI and controls. Post-MI + DM patients had higher TWA values than post-MI
      patients (58 +/- 21 MUV VS 52 +/- 18 MUV, P = 0.029). Impaired HRT--increased TO
      and decreased TS were observed in MI patients with or without DM. During follow
      up of 578 +/- 146 days, cardiac death occurred in ten patients and three of them
      suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT
      positive outcome [HR (95% CI): 5.01, 1.33-18.85; P = 0.017], as well as the
      combination of abnormal TWA (>=47 MUV) and positive HRT had significant
      association with the endpoint [HR (95% CI): 9.08, 2.21-37.2; P = 0.002)].
      CONCLUSION: This study indicates that AECGs-based TWA and HRT can predict cardiac
      mortality in MI patients with or without DM. Combined analysis TWA and HRT may be
      a convenient and useful method of identifying patients at high risk for
      cardiovascular death.

PMID- 22950361
TI  - (Soft) capsules of wisdom: preventing myo-inositol malabsorption caused by
      coffee.

PMID- 22950362
TI  - Correlated magnetic states in extended one-dimensional defects in graphene.
AB  - Ab initio calculations indicate that while the electronic states introduced by
      tilt grain boundaries in graphene are only partially confined to the defect core,
      a translational grain boundary introduces states near the Fermi level that are
      very strongly confined to the core of the defect, and display a ferromagnetic
      instability. The translational boundary lies along a graphene zigzag direction
      and its magnetic state is akin to that which has been theoretically predicted to
      occur on zigzag edges of graphene ribbons. Unlike ribbon edges, the translational
      grain boundary is fully immersed within the bulk of graphene, hence its magnetic
      state is protected from the contamination and reconstruction effects that have
      hampered experimental detection of the magnetic ribbon states. Moreover, our
      calculations suggest that charge transfer between grain boundaries and the bulk
      in graphene is short ranged, with charge redistribution confined to ~5 A from the
      geometric center of the 1D defects.

PMID- 22950363
TI  - Hydrodynamic size-dependent cellular uptake of aqueous QDs probed by fluorescence
      correlation spectroscopy.
AB  - Aqueous quantum dots (QDs) directly synthesized with various thiol ligands have
      been investigated as imaging probes in living cells. However, the effect of the
      surface chemistry of these ligands on QDs' cellular uptakes and their
      intracellular fate remains poorly understood. In this work, four CdTe QDs were
      directly synthesized under aqueous conditions using four different thiols as
      stabilizers and their interactions with cells were investigated. Fluorescence
      correlation spectroscopy (FCS), X-ray photoelectron spectroscopy (XPS), and zeta
      potential measurements on QDs primarily show that the surface structure of these
      QDs is highly dependent on the thiol ligands used in the preparation of QDs'
      precursors, including its layer thicknesses, densities, and surface charges.
      Subsequently, FCS integrated with the maximum-entropy-method-based FCS (MEMFCS)
      was used to investigate the concentration distribution and dynamics of these QDs
      in living A-427 cells. Our findings indicate that QDs' surface characteristics
      affect cell membrane adsorption and subsequent internalization. More critically,
      we show that the cellular uptake of aqueous QDs is dependent on their
      hydrodynamic diameter and might have the potential to escape trapped environments
      to accumulate in the cytoplasm.

PMID- 22950364
TI  - Transcriptomic profiling of proteases and antiproteases in the liver of sexually
      mature hens in relation to vitellogenesis.
AB  - BACKGROUND: Most egg yolk precursors are synthesized by the liver, secreted into
      the blood and transferred into oocytes, to provide nutrients and bioactive
      molecules for the avian embryo. Three hundred and sixteen distinct proteins have
      been identified in egg yolk. These include 37 proteases and antiproteases, which
      are likely to play a role in the formation of the yolk (vitellogenesis), as
      regulators of protein metabolism. We used a transcriptomic approach to define the
      protease and antiprotease genes specifically expressed in the hen liver in
      relation to vitellogenesis by comparing sexually mature and pre-laying chickens
      showing different steroid milieu. RESULTS: Using a 20 K chicken oligoarray, a
      total of 582 genes were shown to be over-expressed in the liver of sexually
      mature hens (1.2 to 67 fold-differences). Eight of the top ten over-expressed
      genes are known components of the egg yolk or perivitelline membrane. This list
      of 582 genes contains 12 proteases and 3 antiproteases. We found that
      "uncharacterized protein LOC419301/similar to porin" (GeneID:419301), an
      antiprotease and "cathepsin E-A-like/similar to nothepsin" (GeneID:417848), a
      protease, were the only over-expressed candidates (21-fold and 35-fold
      difference, respectively) that are present in the egg yolk. Additionally, we
      showed the 4-fold over-expression of "ovochymase-2/similar to oviductin"
      (GeneID:769290), a vitelline membrane-specific protease. CONCLUSIONS: Our
      approach revealed that three proteases and antiproteases are likely to
      participate in the formation of the yolk. The role of the other 12 proteases and
      antiproteases which are over-expressed in our model remains unclear. At least 1/3
      of proteases and antiproteases identified in egg yolk and vitelline membrane
      proteomes are expressed similarly in the liver regardless of the maturity of
      hens, and have been initially identified as regulators of haemostasis and
      inflammatory events. The lack of effect of sex steroids on these genes expressed
      in the liver but the products of which are found in the yolk suggests that these
      may be passively incorporated into the yolk rather than actively produced for
      that purpose. These results raise the question of the biological significance of
      egg yolk proteases and antiproteases, and more generally of all minor proteins
      that have been identified in egg yolk.

PMID- 22950365
TI  - Knowledge of undisclosed corporate authorship ("ghostwriting") reduces the
      perceived credibility of antidepressant research: a randomized vignette study
      with experienced nurses.
AB  - BACKGROUND: There is much concern regarding undisclosed corporate authorship
      ("ghostwriting") in the peer-reviewed medical literature. However, there are no
      studies of how disclosure of ghostwriting alone impacts the perceived credibility
      of research results. FINDINGS: We conducted a randomized vignette study with
      experienced nurses (n = 67), using a fictional study of antidepressant
      medication. The vignette described a randomized controlled trial and gave
      efficacy and adverse effect rates. Participants were randomly assigned to one of
      two authorship conditions, either (a) traditional authorship (n = 35) or (b)
      ghostwritten paper (n = 32), and then completed a perceived credibility scale.
      Our primary hypothesis was that the median perceived credibility score total
      would be lower in the group assigned to the ghostwritten paper. Our secondary
      hypotheses were that participants randomized to the ghostwritten condition would
      be less likely to (a) recommend the medication, and (b) want the psychiatrist in
      the vignette as their own clinician. We also asked respondents to estimate
      efficacy and adverse effect rates for the medication.There was a statistically
      significant difference in perceived credibility among those assigned to the
      ghostwriting condition. This amounted to a difference of 9.0 points on the 35
      point perceived credibility scale as tested through the Mann-Whitney U test.
      There was no statistically significant difference between groups in terms of
      recommending the medication, wanting the featured clinician as their own, or in
      estimates of efficacy or adverse effects (p > .05 for all such comparisons).
      CONCLUSION: In this study, disclosure of ghostwriting resulted in lower perceived
      credibility ratings.

PMID- 22950366
TI  - Thrombin inhibitors from the freshwater cyanobacterium Anabaena compacta.
AB  - Bioassay-guided investigation of the cyanobacterium Anabaena compacta extracts
      afforded spumigin J (1) and the known thrombin inhibitor spumigin A (2). The
      absolute configuration of 1 was analyzed by advanced Marfey's methodology.
      Compounds 1 and 2 inhibited thrombin with EC(50) values of 4.9 and 2.1 MUM, and
      0.7 and 0.2 MUM in the cathepsin B inhibitory assay, respectively. The MM-GBSA
      methodology predicted spumigin A with 2S-4-methylproline as the better thrombin
      inhibitor.

PMID- 22950367
TI  - Magnetite nanoparticles for functionalized textile dressing to prevent fungal
      biofilms development.
AB  - The purpose of this work was to investigate the potential of functionalized
      magnetite nanoparticles to improve the antibiofilm properties of textile
      dressing, tested in vitro against monospecific Candida albicans biofilms.
      Functionalized magnetite (Fe3O4/C18), with an average size not exceeding 20 nm,
      has been synthesized by precipitation of ferric and ferrous salts in aqueous
      solution of oleic acid (C18) and NaOH. Transmission electron microscopy, X-ray
      diffraction analysis, and differential thermal analysis coupled with thermo
      gravimetric analysis were used as characterization methods for the synthesized
      Fe3O4/C18. Scanning electron microscopy was used to study the architecture of the
      fungal biofilm developed on the functionalized textile dressing samples and
      culture-based methods for the quantitative assay of the biofilm-embedded yeast
      cells. The optimized textile dressing samples proved to be more resistant to C.
      albicans colonization, as compared to the uncoated ones; these functionalized
      surfaces-based approaches are very useful in the prevention of wound microbial
      contamination and subsequent biofilm development on viable tissues or implanted
      devices.

PMID- 22950369
TI  - Employing an extended Theory of Planned Behaviour to predict breastfeeding
      intention, initiation, and maintenance in White British and South-Asian mothers
      living in Bradford.
AB  - BACKGROUND: Despite reported differences in breastfeeding rates amongst women of
      different ethnic groups, little research has investigated whether the thoughts
      and feelings (social cognitions) of women from these different groups during
      pregnancy influence their later breastfeeding behaviour. OBJECTIVE: This study
      investigates the extent to which social cognitions (based on the Theory of
      Planned Behaviour; TPB) predict differences in breastfeeding intentions,
      initiation, and maintenance between White British (WB) and South Asian (SA)
      women. DESIGN AND METHODS: Two hundred and fifty women (predominantly WB or SA)
      in the last trimester of pregnancy completed a questionnaire based on the TPB.
      The women were followed up 6 months later and their breastfeeding during the
      previous 6 months was recorded. RESULTS: The TPB predicted significant variance
      in breastfeeding across the sample and was able to account for differences
      between SA and WB women. Affective attitudes (emotional reactions to
      breastfeeding) and moral norms (reactions about whether breastfeeding is right or
      wrong) were the strongest predictors of intentions. Intentions and affective
      attitudes were predictive of breastfeeding initiation, whilst only affective
      attitudes were predictive of breastfeeding maintenance. CONCLUSION: Stronger
      intentions to breastfeed led to higher rates of breastfeeding amongst SA women.
      In turn, intentions were predicted by emotional and moral beliefs about
      breastfeeding, beliefs that were less positive amongst a WB sample. This suggests
      that those tasked with encouraging breastfeeding may need to have a different
      conversation with women about breastfeeding that goes beyond a focus on costs and
      benefits.

PMID- 22950368
TI  - Modeling gene expression using chromatin features in various cellular contexts.
AB  - BACKGROUND: Previous work has demonstrated that chromatin feature levels
      correlate with gene expression. The ENCODE project enables us to further explore
      this relationship using an unprecedented volume of data. Expression levels from
      more than 100,000 promoters were measured using a variety of high-throughput
      techniques applied to RNA extracted by different protocols from different
      cellular compartments of several human cell lines. ENCODE also generated the
      genome-wide mapping of eleven histone marks, one histone variant, and DNase I
      hypersensitivity sites in seven cell lines. RESULTS: We built a novel
      quantitative model to study the relationship between chromatin features and
      expression levels. Our study not only confirms that the general relationships
      found in previous studies hold across various cell lines, but also makes new
      suggestions about the relationship between chromatin features and gene expression
      levels. We found that expression status and expression levels can be predicted by
      different groups of chromatin features, both with high accuracy. We also found
      that expression levels measured by CAGE are better predicted than by RNA-PET or
      RNA-Seq, and different categories of chromatin features are the most predictive
      of expression for different RNA measurement methods. Additionally, PolyA+ RNA is
      overall more predictable than PolyA- RNA among different cell compartments, and
      PolyA+ cytosolic RNA measured with RNA-Seq is more predictable than PolyA+
      nuclear RNA, while the opposite is true for PolyA- RNA. CONCLUSIONS: Our study
      provides new insights into transcriptional regulation by analyzing chromatin
      features in different cellular contexts.

PMID- 22950370
TI  - An analysis of stratagems to reduce drowning deaths of young children in private
      swimming pools and spas in Victoria, Australia.
AB  - This population-based retrospective case series study examined the frequency and
      distribution of protective stratagems (legislatively compliant safety barrier,
      adequate caregiver supervision, water familiarisation and early administration of
      cardiopulmonary resuscitation [CPR]) amongst drowning deaths of young children (0
      4 years) in private swimming pools or spas in Victoria, Australia. In 65.0%
      (52/80) of deaths, none of the four protective stratagems were known to be
      present and there was only one case where all four were known to be present. This
      indicates that if the presence of all four stratagems is increased, this may
      reduce drowning in this age group and setting. While these results are positive,
      further examination of the presence and interaction of these stratagems for
      effectiveness is required. Further research is also warranted to explore the
      impact of enforcement of pool fencing legislation and potential associations
      between water familiarisation and drowning risk. In addition, a consensus on the
      definition of adequate supervision in needed. 

PMID- 22950371
TI  - Exploring pregnancy termination experiences and needs among Malaysian women: a
      qualitative study.
AB  - BACKGROUND: Malaysia has relatively liberal abortion laws in that they permit
      abortions for both physical and mental health cases. However, abortion remains a
      taboo subject. The stagnating contraceptive prevalence rate combined with the
      plunging fertility rate suggests that abortion might be occurring clandestinely.
      This qualitative study aimed to explore the experiences of women and their needs
      with regard to abortion. METHODS: Women from diverse backgrounds were purposively
      selected from an urban family planning clinic in Penang, Malaysia based on
      inclusion criteria of being aged 21 and above and having experienced an induced
      abortion. A semi-structured interview guide consisting of open ended questions
      eliciting women's experiences and needs with regard to abortion were utilized to
      facilitate the interviews. Audio recordings were transcribed verbatim and
      analyzed thematically. RESULTS: Thirty-one women, with ages ranging from 21-43
      years (mean 30.16 +/- 6.41), who had induced surgical/medical abortions were
      recruited from an urban family planning clinic. Ten women reported only to have
      had one previous abortion while the remaining had multiple abortions ranging from
      2-8 times. The findings revealed that although women had abortions, nevertheless
      they faced problems in seeking for abortion information and services. They also
      had fears about the consequences and side effects of abortion and wish to receive
      more information on abortion. Women with post-abortion feelings ranged from no
      feelings to not wanting to think about the abortion, relief, feeling of sadness
      and loss. Abortion decisions were primarily theirs but would seek
      partner/husband's agreement. In terms of the women's needs for abortion, or if
      they wished for more information on abortion, pre and post abortion counseling
      and post-abortion follow up. CONCLUSIONS: The existing abortion laws in Malaysia
      should enable the government to provide abortion services within the law.
      Unfortunately, the study findings show that this is generally not so, most
      probably due to social stigma. There is an urgent need for the government to
      review its responsibility in providing accessible abortion services within the
      scope of the law and to look into the regulatory requirements for such services
      in Malaysia. This study also highlighted the need for educational efforts to make
      women aware of their reproductive rights and also to increase their reproductive
      knowledge pertaining to abortion. Besides the government, public education on
      abortion may also be improved by efforts from abortion providers, advocacy groups
      and related NGOs.

PMID- 22950372
TI  - Response assessment in lymphoma: time to lower the bar?

PMID- 22950373
TI  - Optical factors in the rapid analysis of captive bubbles.
AB  - Bubbles and droplets offer multiple advantages over Langmuir troughs for
      compressing interfacial films. Experiments, however, that manipulate films to
      maintain constant surface tension (gamma) present problems because they require
      feedback. Measurements of bubbles and droplets calculate gamma from the shape of
      the interface, and calculations in real time based on finding the Laplacian shape
      that best fits the interface can be difficult. Faster methods obtain gamma from
      only the height and diameter, but the bubbles and droplets rest against a solid
      support, which obscures one section of the interface and complicates measurements
      of the height. The experiments here investigated a series of optical variables
      that affect the visualized location of the different surfaces for captive
      bubbles. The pitch of the support and camera as well as the collimation of
      illuminating light affected the accuracy of the measured dimensions. The
      wavelength of illumination altered the opacity of turbid subphases and hydrated
      gel used to form the solid support. The width of all visualized edges depended on
      the spectral width and collimation of the illuminating light. The intensity of
      illumination had little effect on the images as long as the grayscale remained
      within the dynamic range of the camera. With optimization of these optical
      factors, the width of all edges narrowed significantly. The surfaces away from
      the solid support approached the infinite sharpness of the physical interface.
      With these changes, the grayscale at the upper interface provided the basis for
      locating all surfaces, which improved real-time measurements based on the height
      and diameter.

PMID- 22950374
TI  - Long-term estrogen treatment of mice with a prothrombotic phenotype induces
      sustained increases in thrombin generation without affecting tissue fibrin
      deposition.

PMID- 22950375
TI  - Comparing apples with oranges: A. M. Beliaev, R. J. Marshall, et al. (2011).
      'Clinical benefits and cost-effectiveness of allogeneic red-blood-cell
      transfusion in severe symptomatic anaemia.' Vox Sang.

PMID- 22950376
TI  - Paroxetine use during pregnancy and perinatal outcomes including types of cardiac
      malformations in Quebec and France: a short communication.
AB  - BACKGROUND: Antidepressants, more specifically SSRIs, represent one example of a
      widely prescribed class of medications in pregnant women for which less than
      adequate pregnancy data have been available since the first drug in this class
      was marketed 20 years ago. Moreover, findings from studies performed after 2005,
      when health governmental authorities issued warnings regarding first trimester
      exposure to paroxetine and the risk of cardiac malformations, may be the result
      of detection bias if physicians were investigating more their pregnant patients
      that used paroxetine than the others. OBJECTIVES: To estimate the prevalence of
      1) paroxetine use during pregnancy, and 2) diagnosed cardiac malformations in the
      Quebec and France populations. METHODS: Two distinct pregnancy databases were
      used for this ecologic study: the Quebec Pregnancy Registry and the French
      EFEMERIS database. RESULTS: In Quebec, among the 109,344 eligible pregnancies,
      1,612 (1.5%) were exposed to paroxetine. Prevalence of paroxetine use during
      pregnancy increased from 0.7% to 1.2% between 1998 and 2003, simultaneously to
      the increase of the prevalence of cardiac malformation diagnoses. In France,
      among 40,317 eligible pregnancies, 173 (0.4%) were exposed to paroxetine; between
      2004 and 2008 the number of paroxetine fillings and cardiac malformation
      diagnoses remained constant. CONCLUSIONS: Despite differences in the Quebec and
      French healthcare systems, increase in paroxetine prevalence use during pregnancy
      was already consistent with an increase in the prevalence of cardiac
      malformations, even before the warning on the risk of cardiac malformations in
      newborns in 2005-2006, limiting the possibility of detection bias.

PMID- 22950377
TI  - In silico prediction of adverse drug reactions and toxicities based on
      structural, biological and clinical data.
AB  - Drug adverse effects (ADEs) and toxicities have been extensively studied from
      chemical structure, genetic, biological systems and clinical perspectives. The
      rapid accumulation of chemical, biological and clinical data are highly useful
      for characterizing and predicting ADEs, and have enabled increasing exploration
      of computational methods as low cost tools for predicting various ADEs and
      toxicities. This article reviews the strategies, current progresses, underlying
      difficulties and future prospects in using computational methods for predicting
      ADEs and toxicities.

PMID- 22950378
TI  - Quetiapine induced hypomania: a case report and a review of the literature.
AB  - OBJECTIVES: The 5-HT2 antagonistic action of quetiapine may disinhibit the
      dopaminergic system enhancing dopaminergic activity in the forebrain and
      influencing the mood state. Our objective is to investigate the possible
      induction of manic symptoms by quetiapine through a case report and a review of
      the literature. METHOD: We report the case of a 54 year old woman suffering from
      bipolar depression who developed hypomania seven weeks after the initiation of
      300 mg/d of quetiapine. A literature review concerning the induction of hypomania
      or mania by quetiapine have retrieved the presence of seven similar case reports
      or series. RESULTS: Available literature points toward an early induction of
      hypomania or mania with low dosage of quetiapine treatment (between 100 and 400
      mg/day never exceeding 600 mg/day). Hypomania or mania are possible short term
      complications that can be present few days to few weeks of treatment initiation.
      The discontinuation of the drug or the increase of its dose seems to reverse the
      hypomanic or manic symptoms. Patients described in the literature suffer mostly
      from schizophrenia. CONCLUSION: The atypical antipsychotic drug quetiapine, which
      have antidepressant properties at low doses via its indirect dopamine enhancing
      activity due its serotoninergic antagonism, appears to be involved in the
      induction of rare hypomanic or manic state in patients suffering from bipolar
      disorders and to have mood stabilizing properties at higher doses when its
      dopamine antagonist activity becomes more prominent. Its manic/hypomanic
      induction properties should not prevent its administration to patients suffering
      from bipolar disorder.

PMID- 22950379
TI  - Specific TNF-alpha inhibition in cerebral aneurysm formation and subarachnoid
      hemorrhage.
AB  - The signal transduction of tumor necrosis factor-alpha (TNF-alpha) is complex and
      regulated via a vast number of interconnecting pathways. The TNF-alpha signaling
      pathway plays a major role in the pathogenesis of subarachnoid hemorrhage (SAH).
      The advent of molecular mimicry has provided a number of opportunities to tackle
      disease with improved specificity. Here we review the mechanisms of their action
      and the potential for TNF-alpha inhibitors as a treatment for subarachnoid
      hemorrhage. Searches were performed using PubMed with the search terms
      "subarachnoid haemorrhage", "TNF alpha", "novel drugs" TNF alpha inhibition",
      "management", "cerebral aneurysm", and "vasospasm" from 1970 to February, 2012.
      Articles were also identified through searches of the Cochrane library and
      searches of the authors' own files. Only papers published in English were
      reviewed. In conclusion, there is considerable theoretical evidence for the
      potential of TNF-alpha inhibitors to impact on the pathogenesis of aneurismal
      SAH. Such indications demonstrate the potential for specific targeting of
      molecular signaling pathways to prevent the growth and rupture of cerebral
      aneurysm.

PMID- 22950380
TI  - Non-steroidal anti-inflammatory drugs used as a treatment modality in
      subarachnoid hemorrhage.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently
      prescribed therapies worldwide. Meta-analysis data indicate the potential for
      myocardial infarction, cerebrovascular incident, heart failure, renal failure and
      arterial hypertension. Here we review the mechanisms of their actions and the
      potential for therapeutic use in subarachnoid hemorrhage. Searches were performed
      using PubMed with the search terms "subarachnoid hemorrhage", "NSAID",
      "treatment", "management", "cerebral aneurysm", and "vasospasm" from 1970 to
      February, 2012. Articles were also identified through searches of the Cochrane
      library and searches of the authors' own files. Only papers published in English
      were reviewed.There are considerably mixed views on the potential impact of
      NSAIDs on the treatment and prevention of SAH. Whilst theoretically, the
      potential for positive intervention in the condition is huge, little effect
      appears to be measurable in clinical practice.

PMID- 22950381
TI  - Exploring the use of estrogen & progesterone replacement therapy in subarachnoid
      hemorrhage.
AB  - The hypothesis that alterations in hormone levels can impact on subarachnoid
      hemorrhage (SAH) is rapidly gaining momentum. Specifically, the concept that post
      menopausal women are more susceptible to the condition has convinced many of the
      protective roles of estrogen and progesterone. Here we review the mechanisms of
      their actions and the potential for estrogen and progesterone replacement therapy
      in subarachnoid hemorrhage. Searches were performed using PubMed with the search
      terms "subarachnoid hemorrhage", "estrogen", "progesterone "treatment",
      "management", "cerebral aneurysm", and "vasospasm" from 1970 to February, 2012.
      Articles were also identified through searches of the Cochrane library and
      searches of the authors' own files. Only papers published in English were
      reviewed. In conclusion, there is significant theoretical evidence for the
      potential role of estrogen and progesterone use in altering the pathogenesis of
      SAH. Nevertheless, this has received mixed reviews in both case controlled
      studies and cohort analysis within the literature.

PMID- 22950382
TI  - Correlation of CYP2B6-516G > T Polymorphism with Plasma Efavirenz Concentration
      and Depression in HIV-Infected Adults in Northern Thailand.
AB  - BACKGROUND: Single nucleotide polymorphism of the hepatic cytochrome P450
      isoenzyme 2B6 (CYP2B6) gene is a cause of variation in plasma efavirenz (EFV)
      concentrations. We aimed to determine the allelic distribution of CYP2B6 gene,
      plasma levels of EFV, the prevalence of clinical depression, and their
      correlations in northern Thai population. METHODS: This was a cross-sectional
      study of HIV-infected patients on EFV-containing antiretroviral regimens for >=48
      weeks. A single blood specimen was collected for determination of the mid-dose
      plasma EFV concentration and CYP2B6- 516G > T polymorphism. The presence and
      severity of depression were assessed. RESULTS: One hundred patients were enrolled
      [mean age (+/-SD) was 41.81+/-8.44 years, mean CD4 lymphocyte count 462+/-193
      cells/ul]. The genotype CYP2B6-516 guanine/guanine (G/G), guanine/thymidine
      (G/T), and T/T were found in 49%, 37%, and 14% of patients, respectively. The
      allele frequency of CYP2B6-516 G to T replacement was 32.5%. The median plasma
      EFV concentration was 2,616 ng/mL (IQR 1,851-3,742); 79% had EFV plasma
      concentrations from 1,000 to 4,000 ng/mL. The mean EFV concentrations for those
      with G/G, G/T and T/T genotypes were 2,082+/-630, 3,166+/-1,074, and 11,196+/
      6,265 ng/mL, respectively (p < 0.01). CYP2B6-516G > T polymorphism was the only
      factor associated with high plasma EFV levels. Nineteen patients had depression;
      13 of 18 (72%) with mild and one with major depression had normal plasma EFV
      level. A weak correlation between plasma EFV concentrations and depression scores
      was observed (p=0.009, R2=0.059). CONCLUSIONS: The prevalence of CYP2B6-516G > T
      polymorphism in northern Thai population is high and strongly associated with
      inter-individual drug levels variation.

PMID- 22950384
TI  - Isoflurane facilitates synaptic NMDA receptor endocytosis in mice primary
      neurons.
AB  - Inhalation anesthetic isoflurane has been reported to induce caspase activation
      and accumulation of beta-amyloid (Abeta), however, the down-stream consequences
      of these effects are largely unknown. Isoflurane has also been shown to impair
      learning and memory, however, the up-stream mechanisms of these effects remain
      largely to be determined. Facilitation of synaptic NMDA receptor endocytosis can
      reduce synaptic function, leading to learning and memory impairment. We therefore
      set out to determine the effects of isoflurane on synaptic NMDA receptor
      endocytosis. Primary neurons from wild-type and Alzheimer's disease transgenic
      mice were treated with 2% isoflurane for six hours. Synaptic surface levels of
      NMDA receptor 2B (NR2B) and NR2B internalization were determined by surface and
      cleavable biotinylation assay, western blot analysis and immunofluorescence. Here
      we show that isoflurane can induce caspase-3 activation, increase levels of beta
      site amyloid precursor protein-cleaving enzyme and cause accumulation of Abeta in
      the primary neurons. Isoflurane facilitates synaptic NR2B endocytosis as
      evidenced by reducing surface NR2B levels, increasing NR2B internalization, and
      decreasing the ratio of synaptic surface NR2B to synapsin in mice primary
      neurons. Moreover, caspase activation inhibitor Z-VAD and gamma-secretase
      inhibitor L-685,458 attenuated the isoflurane-facilitated NR2B endocytosis. These
      results suggest that isoflurane induces caspase activation and Abeta
      accumulation, leading to facilitation of synaptic NMDA receptor endocytosis,
      which potentially serve as the upstream mechanism of the isoflurane-induced
      impairment of learning and memory. These findings will encourage further studies
      to determine the underlying mechanism by which isoflurane and other anesthetics
      promote Alzheimer's disease neuropathogenesis and induce cognitive dysfunction.

PMID- 22950383
TI  - NFAT gene family in inflammation and cancer.
AB  - Calcineurin-NFAT signaling is critical for numerous aspects of vertebrate
      function during and after embryonic development. Initially discovered in T cells,
      the NFAT gene family, consisting of five members, regulates immune system,
      inflammatory response, angiogenesis, cardiac valve formation, myocardial
      development, axonal guidance, skeletal muscle development, bone homeostasis,
      development and metastasis of cancer, and many other biological processes. In
      this review we will focus on the NFAT literature relevant to the two closely
      related pathological systems: inflammation and cancer.

PMID- 22950385
TI  - Metformin use and improved response to therapy in esophageal adenocarcinoma.
AB  - BACKGROUND: We investigated the radiographic and pathologic response rate of
      esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients
      taking metformin. MATERIAL AND METHODS: Two hundred eighty-five patients with
      esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed
      by esophagectomy from 1997 to 2012 were included in the study, including 29
      diabetics taking metformin, 21 diabetics not taking metformin and 235 non
      diabetics. Pre- and post-treatment positron emission tomography (PET) scans were
      available for 204 patients. Pathologic response was graded at the time of
      surgery. Response rates were compared using both the chi(2) statistic as well as
      ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was
      performed to control for predictors of pathologic complete response (CR) after
      CRT. RESULTS: The overall rate of pathologic CR for the study population was 20%.
      The pathologic CR rate was higher in patients taking metformin (34.5%), compared
      to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic
      patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with >=
      1500 mg/d associated with a higher CR rate. No significant difference seen in pre
      CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly
      decreased in patients taking metformin (p = 0.05). On multivariate logistic
      regression, metformin use was independently associated with pathologic CR (p =
      0.04). Metformin use was also associated with decreased in field loco-regional
      failure following radiation (p = 0.05). CONCLUSION: Metformin use is associated
      with a dose-dependent increased response to CRT in esophageal cancer and may be a
      sensitizer to this therapy.

PMID- 22950386
TI  - Dose-volume histogram analysis for risk factors of radiation-induced rib fracture
      after hypofractionated proton beam therapy for hepatocellular carcinoma.
AB  - BACKGROUND: Radiation-induced rib fracture has been reported as a late
      complication after external radiotherapy to the chest. The purpose of this study
      was to clarify the characteristics and risk factors of rib fracture after
      hypofractionated proton beam therapy (PBT). MATERIAL AND METHODS: The
      retrospective study comprised 67 patients with hepatocellular carcinoma who were
      treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We
      analyzed the patients' characteristics and determined dose-volume histograms
      (DVHs) for the irradiated ribs, and then estimated relationships between risk of
      fracture and several dose-volume parameters. An irradiated rib was defined to be
      any rib included in the area irradiated by PBT as determined by treatment
      planning computed tomography. RESULTS: Among the 67 patients, a total of 310 ribs
      were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs
      developed fractures in 11 patients (16.4%). No significant relationships were
      seen between incidence of fracture and characteristics of patients, including
      sex, age, tumor size, tumor site, and follow-up period (p >= 0.05). The results
      of receiver operating characteristic curve analysis using DVH parameters
      demonstrated that the largest area under the curve (AUC) was observed for the
      volume of rib receiving a biologically effective dose of more than 60 Gy(3 )(RBE)
      (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy(3)] and the AUCs of
      V30 to V120 (EQD2; 18-72 Gy(3)) and Dmax to D(10 cm)(3) were similar to that of
      V60. No significant relationships were seen for DVH parameters and intervals from
      PBT to incidence of fracture. CONCLUSION: DVH parameters are useful in predicting
      late adverse events of rib irradiation. This study identified that V60 was a most
      statistically significant parameter, and V30 to V120 and Dmax to D(10 cm)(3) were
      also significant and clinically useful for estimating the risk of rib fracture
      after hypofractionated PBT.

PMID- 22950388
TI  - Lessons from liver transplantation.

PMID- 22950387
TI  - A literature-based meta-analysis of clinical risk factors for development of
      radiation induced pneumonitis.
AB  - INTRODUCTION: The risk of developing side effects after radiotherapy is not only
      dependent on radiation dose, but may also be affected by patient-related risk
      factors. Here we perform a literature-based meta-analysis to estimate the effect
      of various clinical risk factors on the incidence of symptomatic radiation
      pneumonitis (RP). MATERIAL AND METHODS: A systematic review of English language
      articles in the Pubmed, Embase and Cochrane controlled trials registers. Studies
      with the mesh term "radiation pneumonitis" or the search term "radiation
      pneumonitis" were included. Additional studies were identified by manual
      searching of the references. Studies reporting crude incidence or odds ratios
      (OR) for radiation pneumonitis vs. age, disease location, smoking status,
      chemotherapy schedule or comorbidity were included. A systematic overview (meta
      analysis) was conducted to synthesize data across multiple studies. RESULTS:
      Significant risk factors for RP were: older age (OR = 1.7, p < 0.0001); disease
      located in mid-lower lung (OR = 1.9, p = 0.002); presence of comorbidity (OR =
      2.3, p = 0.007). Ongoing smoking was found to protect against RP (OR = 0.6, p =
      0.008). History of smoking tended to protect against RP (OR = 0.7, p = 0.06).
      Sequential (rather than concomitant) chemotherapy scheduling (OR = 1.6, p = 0.01)
      increased RP risk, but treatment intensity and patients selection are likely
      confounders. CONCLUSION: This systematic overview revealed several clinical risk
      factors for RP that have not been unambiguously identified in the literature.
      These risk factors should be considered when defining dose-volume constraints for
      radiation treatment plan optimization.

PMID- 22950389
TI  - Death by regional block: can the analgesic benefits ever outweigh the risks?

PMID- 22950390
TI  - A comparison of intra-operative blood loss and acid-base balance between
      vasopressor and inotrope strategy during living donor liver transplantation: a
      randomised, controlled study.
AB  - Administration of vasopressors or inotropes during liver transplant surgery is
      almost universal, as this procedure is often accompanied by massive haemorrhage,
      acid-base imbalance, and cardiovascular instability. However, the actual agents
      that should be used and the choice between a vasopressor and an inotrope strategy
      are not clear from existing published evidence. In this prospective, randomised,
      controlled and single-blinded study, we compared the effects of a vasopressor
      strategy on intra-operative blood loss and acid-base status with those of an
      inotrope strategy during living donor liver transplantation. Seventy-six adult
      liver recipients with decompensated cirrhosis were randomly assigned to receive a
      continuous infusion of either phenylephrine at a dose of 0.3-0.4 MUg.kg(-1).min(
      1) or dopamine and/or dobutamine at 2-8 MUg.kg(-1).min(-1) during surgery.
      Vascular resistance was higher over time in the phenylephrine group than in the
      dopamine/dobutamine group. Estimated blood loss was significantly lower in the
      phenylephrine group than in the dopamine/dobutamine group (mean (SD) 4.5 (1.8) l
      vs 6.1 (3.4) l, respectively, p=0.011). Patients in the phenylephrine group had
      lower lactate levels in the late pre-anhepatic and the early anhepatic phase and
      needed less bicarbonate administration than those in the dopamine/dobutamine
      group (median (IQR [range]) 40 (0-100 [0-160]) mEq vs 70 (40-163 [0-260]) mEq,
      respectively, p=0.018). Postoperative clinical outcomes and laboratory-measured
      hepatic and renal function did not differ between the groups. Increased vascular
      resistance and reduction of portal blood flow by intra-operative phenylephrine
      infusion is assumed to decrease the amount of intra-operative bleeding and
      thereby ameliorate the progression of lactic acidosis during liver transplant
      surgery.

PMID- 22950391
TI  - Catastrophic complication of an interscalene catheter for continuous peripheral
      nerve block analgesia.
AB  - We report a catastrophic postoperative complication of a prolonged interscalene
      block performed under general anaesthesia. The course of the anaesthetic was
      uneventful and the patient remained stable during his stay in the recovery area
      with the operative extremity paralysed and insensate. No further local
      anaesthetic was administered until later that day when the patient received 10 ml
      bupivacaine 0.25% through the catheter. Upon completion of the top-up dose, no
      change in the patient's status was noticed. The patient was next assessed 6.5 h
      later when he was found dead in his bed. A postmortem CT scan revealed the
      catheter to be sited intrathecally, presumably the result of dural sleeve
      penetration.

PMID- 22950392
TI  - The 'Magic Eye(r)' method of rhythm assessment.

PMID- 22950393
TI  - 'Optimal' catheter positions in the superior vena cava?

PMID- 22950394
TI  - Labetalol for hypertensive pulmonary oedema in pregnancy.

PMID- 22950396
TI  - Variation in costs of emergency laparotomy following a multicentre national
      audit.

PMID- 22950397
TI  - Sugammadex and rocuronium-induced anaphylaxis.

PMID- 22950398
TI  - Plethysmographic variability index: everywhere for everyone?

PMID- 22950402
TI  - Medical simulation in 'my world'.

PMID- 22950403
TI  - Systematic underestimation of blood loss.

PMID- 22950404
TI  - Is the Blood Loss Score universally acceptable?

PMID- 22950407
TI  - Anaesthesia machine check.

PMID- 22950408
TI  - Measurement of forces during direct laryngoscopy and videolaryngoscopy.

PMID- 22950410
TI  - Common inversion polymorphism at 17q21.31 affects expression of multiple genes in
      tissue-specific manner.
AB  - BACKGROUND: Chromosome 17q21.31 contains a common inversion polymorphism of
      approximately 900 kb in populations with European ancestry. Two divergent MAPT
      haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns
      across the region reflecting the inversion status at this locus. The MAPT H1
      haplotype has been associated with progressive supranuclear palsy, corticobasal
      degeneration, Parkinson's disease and Alzheimer's disease, while the H2 is linked
      to recurrent deletion events associated with the 17q21.31 microdeletion syndrome,
      a disease characterized by developmental delay and learning disability. RESULTS:
      In this study, we investigate the effect of the inversion on the expression of
      genes in the 17q21.31 region. We find the expression of several genes in and at
      the borders of the inversion to be affected; specific either to whole blood or
      different regions of the human brain. The H1 haplotype was found to be associated
      with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a
      decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1.
      CONCLUSIONS: Studies thus far have focused on the expression of MAPT in the
      inversion region. However, our results show that the inversion status affects
      expression of other genes in the 17q21.31 region as well. Given the link between
      the inversion status and different neurological diseases, these genes may also be
      involved in disease pathology, possibly in a tissue-specific manner.

PMID- 22950412
TI  - "Primum non nocere": the addition of granulocyte-macrophage colony stimulating
      factor to alemtuzumab in chronic lymphocytic leukemia.

PMID- 22950411
TI  - Synthetic metabolic engineering-a novel, simple technology for designing a
      chimeric metabolic pathway.
AB  - BACKGROUND: The integration of biotechnology into chemical manufacturing has been
      recognized as a key technology to build a sustainable society. However, the
      practical applications of biocatalytic chemical conversions are often restricted
      due to their complexities involving the unpredictability of product yield and the
      troublesome controls in fermentation processes. One of the possible strategies to
      overcome these limitations is to eliminate the use of living microorganisms and
      to use only enzymes involved in the metabolic pathway. Use of recombinant
      mesophiles producing thermophilic enzymes at high temperature results in
      denaturation of indigenous proteins and elimination of undesired side reactions;
      consequently, highly selective and stable biocatalytic modules can be readily
      prepared. By rationally combining those modules together, artificial synthetic
      pathways specialized for chemical manufacturing could be designed and
      constructed. RESULTS: A chimeric Embden-Meyerhof (EM) pathway with balanced
      consumption and regeneration of ATP and ADP was constructed by using nine
      recombinant E. coli strains overproducing either one of the seven glycolytic
      enzymes of Thermus thermophilus, the cofactor-independent phosphoglycerate mutase
      of Pyrococcus horikoshii, or the non-phosphorylating glyceraldehyde-3-phosphate
      dehydrogenase of Thermococcus kodakarensis. By coupling this pathway with the
      Thermus malate/lactate dehydrogenase, a stoichiometric amount of lactate was
      produced from glucose with an overall ATP turnover number of 31. CONCLUSIONS: In
      this study, a novel and simple technology for flexible design of a bespoke
      metabolic pathway was developed. The concept has been testified via a non-ATP
      forming chimeric EM pathway. We designated this technology as "synthetic
      metabolic engineering". Our technology is, in principle, applicable to all
      thermophilic enzymes as long as they can be functionally expressed in the host,
      and thus would be potentially applicable to the biocatalytic manufacture of any
      chemicals or materials on demand.

PMID- 22950413
TI  - Recognition of platinum-DNA adducts by HMGB1a.
AB  - Cisplatin (CP) and oxaliplatin (OX), platinum-based drugs used widely in
      chemotherapy, form adducts on intrastrand guanines (5'GG) in genomic DNA. DNA
      damage recognition proteins, transcription factors, mismatch repair proteins, and
      DNA polymerases discriminate between CP- and OX-GG DNA adducts, which could
      partly account for differences in the efficacy, toxicity, and mutagenicity of CP
      and OX. In addition, differential recognition of CP- and OX-GG adducts is highly
      dependent on the sequence context of the Pt-GG adduct. In particular, DNA binding
      protein domain HMGB1a binds to CP-GG DNA adducts with up to 53-fold greater
      affinity than to OX-GG adducts in the TGGA sequence context but shows much
      smaller differences in binding in the AGGC or TGGT sequence contexts. Here,
      simulations of the HMGB1a-Pt-DNA complex in the three sequence contexts revealed
      a higher number of interface contacts for the CP-DNA complex in the TGGA sequence
      context than in the OX-DNA complex. However, the number of interface contacts was
      similar in the TGGT and AGGC sequence contexts. The higher number of interface
      contacts in the CP-TGGA sequence context corresponded to a larger roll of the Pt
      GG base pair step. Furthermore, geometric analysis of stacking of phenylalanine
      37 in HMGB1a (Phe37) with the platinated guanines revealed more favorable
      stacking modes correlated with a larger roll of the Pt-GG base pair step in the
      TGGA sequence context. These data are consistent with our previous molecular
      dynamics simulations showing that the CP-TGGA complex was able to sample larger
      roll angles than the OX-TGGA complex or either CP- or OX-DNA complexes in the
      AGGC or TGGT sequences. We infer that the high binding affinity of HMGB1a for CP
      TGGA is due to the greater flexibility of CP-TGGA compared to OX-TGGA and other
      Pt-DNA adducts. This increased flexibility is reflected in the ability of CP-TGGA
      to sample larger roll angles, which allows for a higher number of interface
      contacts between the Pt-DNA adduct and HMGB1a.

PMID- 22950414
TI  - Integrating pathology and radiology disciplines: an emerging opportunity?
AB  - Pathology and radiology form the core of cancer diagnosis, yet the workflows of
      both specialties remain ad hoc and occur in separate "silos," with no direct
      linkage between their case accessioning and/or reporting systems, even when both
      departments belong to the same host institution. Because both radiologists' and
      pathologists' data are essential to making correct diagnoses and appropriate
      patient management and treatment decisions, this isolation of radiology and
      pathology workflows can be detrimental to the quality and outcomes of patient
      care. These detrimental effects underscore the need for pathology and radiology
      workflow integration and for systems that facilitate the synthesis of all data
      produced by both specialties. With the enormous technological advances currently
      occurring in both fields, the opportunity has emerged to develop an integrated
      diagnostic reporting system that supports both specialties and, therefore,
      improves the overall quality of patient care.

PMID- 22950415
TI  - Clinical significance of Koebner phenomenon in vitiligo.
AB  - BACKGROUND: The clinical significance of Koebner phenomenon (KP) in vitiligo with
      respect to disease activity and course is still debatable. Recently, a new
      classification was introduced for the assessment of KP. OBJECTIVES: To evaluate
      the new assessment method for KP in clinical practice and to determine its
      clinical significance, both with respect to the clinical profile, course of
      vitiligo and treatment response. METHODS: Seven hundred patients with generalized
      vitiligo were included in this observational cohort study. KP was classified
      according to the new classification system into different subtypes [KP1, by
      history; KP2A and KP2B, by clinical examination (A, lesions on friction areas; B,
      linear, artefactual lesions)]. RESULTS: KP1 was positive in 34.1% of the
      patients, 66.3% were KP2A positive and 15.1% showed KP2B. The body surface area
      (BSA) was significantly (P < 0.001) higher in the presence of any KP subtype and
      more disease activity was found in KP1-positive and KP2B-positive patients. An
      earlier age at onset and elevated risk of further depigmentation despite
      treatment were observed in all KP-positive groups. In KP2A- and KP2B-positive
      patients, depigmentation of wrists/ankles was more common. In the KP2A-positive
      group, a significantly higher prevalence of thyroid disease was found while
      autoimmune diseases were less prevalent in KP2B-positive patients. CONCLUSION:
      The new assessment method for KP, taking into account both history and clinical
      examination, seems to be a useful and valuable tool for assessing KP in daily
      practice. Our results support the hypothesis that KP may function as a clinical
      parameter to assess and predict the clinical profile and course of vitiligo.

PMID- 22950416
TI  - A nationwide, population-based, long-term follow-up study of repeated self-harm
      in Taiwan.
AB  - BACKGROUND: Previous follow-up studies of repeated self-harm show that the
      cumulative risk of repeated self-harm within one year is 5.7%-15%, with females
      at greatest risk. However, relatively few studies have focused on the Far East.
      The objective of this study was to calculate the cumulative risk of repeated self
      harm over different lengths of follow-up time (3 months, 6 months, and 1-8
      years), to determine factors influencing repeated self-harm and to explore the
      interaction between gender and self-harm methods. METHODS: We used self-harm
      patient who hospitalized due to first-time self-harm between 2000 and 2007 from
      1,230 hospitals in Taiwan. Hospitalization for repeated self-harm among members
      of this cohort was tracked after 3 months, 6 months, and 1-8 years. Tracking
      continued until December 31, 2008. We analyzed the cumulative risk and risk
      factors of repeated self-harm by using negative binomial regression. RESULTS: Of
      the 39,875 individual study samples, 3,388 individuals (8.50%) were found to have
      repeatedly self-harmed. The cumulative risk of repeated self-harm within three
      months was 7.19% and within one year was 8%. Within 8 years, it was 8.70%.
      Females were more likely to repeatedly self-harm than males (RR = 1.21, 95% CI =
      1.15-1.76). The main method of self-harm was solid or liquid substances (RR =
      1.88, 95% CI = 1.23-2.04) or cutting or piercing (RR = 1.36, 95% CI = 1.02-1.82),
      and in patients with psychiatric disorders were more likely to self-harm (RR =
      1.61, 95% CI = 1.48-1.75). CONCLUSIONS: The key time for intervention for
      repeated self-harm is within three months. Appropriate prevention programs should
      be developed based on gender differences.

PMID- 22950417
TI  - An "aprotic" Tamao oxidation/syn-selective tautomerization reaction for the
      efficient synthesis of the C1-C9 fragment of fludelone.
AB  - An efficient synthesis of the C(1)-C(9) fragment of fludelone has been developed.
      The key step is a tandem silylformylation-crotylsilylation/Tamao oxidation
      sequence that establishes the C(5) ketone, the C(6), C(7), and C(8)
      stereocenters, and the C(9) alkene in a single operation from a readily accessed
      starting material. The stereochemical outcome at C(6) depends critically on the
      development of an "aprotic" Tamao oxidation, which leads to a reversal in the
      intrinsic diastereoselectivity observed using "standard" Tamao oxidation
      conditions.

PMID- 22950419
TI  - Effect of different postharvest temperatures on the accumulation of sugars,
      organic acids, and amino acids in the juice sacs of Satsuma mandarin (Citrus
      unshiu Marc.) fruit.
AB  - To elucidate the effect of different postharvest temperatures on the accumulation
      of sugars, organic acids, and amino acids and to determine the best temperature
      to minimize their postharvest change, their content after harvest was
      investigated at 5, 10, 20, and 30  degrees C for 14 days in the juice sacs of
      Satsuma mandarin (Citrus unshiu Marc. cv. Aoshima-unshiu) fruit. In all sugars,
      the changes were negligible at all temperatures. Organic acids decreased slightly
      at all temperatures, with the exception of malic acid at 30  degrees C, which
      increased slightly. Two amino acids, ornithine and glutamine, increased at 5 
      degrees C, but they did not increase at other temperatures. In 11 amino acids
      (phenylalanine, tryptophan, tyrosine, isoleucine, leucine, valine, threonine,
      lysine, methionine, histidine, and gamma-amino butyric acid), the content was
      higher at 20 and 30  degrees C than at other temperatures. Thus, the content of
      amino acids was more variable than that of sugars and organic acids in response
      to temperatures. Moreover, amino acids responded to temperature differently: two
      amino acids were cold responsive, and 11 were heat-responsive. The best
      temperature to minimize the postharvest changes in amino acid profiles in the
      juice sacs of Aoshima-unshiu was 10  degrees C. The responsiveness to
      temperatures in two cold-responsive (ornithine and glutamine) and five heat
      responsive (phenylalanine, tryptophan, valine, lysine, and histidine) amino acids
      was conserved among three different Satsuma mandarin cultivars, Aoshima-unshiu
      (late-maturing cultivar), Silverhill (midmaturing cultivar), and Miyagawa-wase
      (early-maturing cultivar). The metabolic responsiveness to temperature stress was
      discussed on the basis of the changes in the amino acid profile.

PMID- 22950420
TI  - Endothelial cell protein C receptor-mediated redistribution and tissue-level
      accumulation of factor VIIa.
AB  - BACKGROUND: Recent studies show that activated factor VII (FVIIa) binds to the
      endothelial cell protein C receptor (EPCR) on the vascular endothelium; however,
      the importance of this interaction in hemostasis or pathophysiology is unknown.
      OBJECTIVE: The aim of the present study was to investigate the role of the FVIIa
      interaction with EPCR on the endothelium in mediating FVIIa transport from the
      circulation to extravascular tissues. METHODS: Wild-type, EPCR-deficient or ECPR
      over-expressing mice were injected with human recombinant (r)FVIIa (120 MUg kg(
      1) body weight) via the tail vein. At varying time intervals after rFVIIa
      administration, blood and various tissues were collected to measure FVIIa antigen
      and activity levels. Tissue sections were analyzed by immunohistochemistry for
      FVIIa and EPCR. RESULTS: The data reveal that, after intravenous (i.v.)
      injection, rFVIIa rapidly disappears from the blood and associates with the
      endothelium in an EPCR-dependent manner. Immunohistochemical analyses revealed
      that the association of FVIIa with the endothelium was maximal at 30 min and
      thereafter progressively declined. The FVIIa association with the endothelium was
      undetectable at time points exceeding 24 h post-FVIIa administration. The levels
      of rFVIIa accumulated in tissue correlate with expression levels of EPCR in mice
      and FVIIa associated with tissues remained functionally active for periods of at
      least 7 days. CONCLUSIONS: The observation that an EPCR-dependent association of
      FVIIa with the endothelium is most pronounced soon after rFVIIa administration
      and subsequently declines temporally, combined with the retention of functionally
      active FVIIa in tissue homogenates for extended periods, indicates that FVIIa
      binding to EPCR on the endothelium facilitates the transport of FVIIa from
      circulation to extravascular tissues where TF resides.

PMID- 22950421
TI  - Linkage disequilibrium and haplotype analysis of the ATP7B gene in Alzheimer's
      disease.
AB  - Copper dyshomeostasis leading to a labile Cu(2+) not bound to ceruloplasmin
      ("free" copper) may influence Alzheimer's disease (AD) onset or progression. To
      investigate this hypothesis, we investigated ATP7B, the gene that controls copper
      excretion through the bile and concentrations of free copper in systemic
      circulation. Our study analyzed informative ATP7B single-nucleotide polymorphisms
      (SNPs) in a case-control population (n=515). In particular, we evaluated the
      genetic structure of the ATP7B gene using the HapMap database and carried out a
      genetic association investigation. Linkage disequilibrium (LD) analysis
      highlighted that our informative SNPs and their LD SNPs covered 96% of the ATP7B
      gene sequence, distinguishing two "strong LD" blocks. The first LD block contains
      the gene region encoding for transmembrane and copper-binding, whereas the second
      LD block encodes for copper-binding domains. The genetic association analysis
      showed significant results after multiple testing correction for all investigated
      variants (rs1801243, odds ratio [OR]=1.52, 95% confidence interval [CI]=1.10
      2.09, p=0.010; rs2147363, OR=1.58, 95% CI=1.11-2.25, p=0.010; rs1061472, OR=1.73,
      95% CI=1.23-2.43, p=0.002; rs732774, OR=2.31, 95% CI=1.41-3.77, p<0.001),
      indicating that SNPs in transmembrane domains may have a stronger association
      with AD risk than variants in copper-binding domains. Our study provides novel
      insights that confirm the role of ATP7B as a potential genetic risk factor for
      AD. The analysis of ATP7B informative SNPs confirms our previous hypothesis about
      the absence of ATP7B in the significant loci of genome-wide association studies
      of AD and the genetic association study suggests that transmembrane and adenosine
      triphosphate (ATP) domains in the ATP7B gene may harbor variants/haplotypes
      associated with AD risk.

PMID- 22950423
TI  - MxA polymorphisms are associated with risk and age-at-onset in Alzheimer disease
      and accelerated cognitive decline in Chinese elders.
AB  - Alzheimer disease (AD) is the most common neurodegenerative disease, and
      inflammation has been associated with the pathogenesis of AD. The myxovirus
      resistance protein 1 (MxA) is an interferon-induced antiviral protein and is
      widely studied in virus-caused diseases. An immunohistochemical study has shown
      MxA expression in senile plaques of the AD brain, suggesting that MxA might be
      involved in the pathogenesis of AD. In this study, 10 tagged single-nucleotide
      polymorphisms (SNPs) and two commonly studied SNPs in the MxA gene were
      investigated in 220 AD patients and 316 age-matched healthy Chinese subjects to
      investigate the association to the predisposition and age of onset (AAO) of AD.
      Healthy subjects were followed up for 2 years to determine the association of MxA
      polymorphisms and the rate of cognitive deterioration. Our result showed
      rs17000900 (MxA-123) and rs461093 were significantly associated with the risk of
      AD. Six MxA SNPs, including MxA -123, were associated to AAO of AD. The carriers
      of minor alleles of five MxA SNPs, including rs457274, rs2071430 (MxA -88),
      rs461093, rs469083, and rs1557372, were associated with faster cognitive decline
      over 2 years. Furthermore, our functional assay showed significant association
      between increased MxA expression and the -123A/-88T haplotype, which is in line
      with our findings in genetic association. This is the first study showing the
      significant association of MxA SNPs and predisposition of AD, modulation of AAO
      in AD, and rate of cognitive decline.

PMID- 22950422
TI  - Relationship between renal function and physical performance in elderly
      hospitalized patients.
AB  - Chronic kidney disease (CKD) is increasingly recognized as a cause of worsening
      physical functioning in older patients. The Short Physical Performance Battery
      (SPPB) is highly reliable in older populations, but no data on older hospitalized
      patients with different degrees of kidney function are available. We aimed at
      testing the association between estimated glomerular filtration rate (eGFR) and
      SPPB, either global score (range 0-12) or its individual components (muscle
      strength, balance, and walking speed, each ranging from 0 to 4), in a sample of
      older hospitalized patients. Our series consisted of 486 patients aged 65 or more
      consecutively enrolled in 11 acute care medical wards participating to a
      multicenter observational study. eGFR was obtained by the Chronic Kidney Disease
      Epidemiological Collaboration (CKD-EPI) equation. Physical performance was
      objectively measured by the SPPB. The relationship between eGFR and SPPB was
      investigated by multiple linear regression analysis. Physically impaired patients
      (SPPB total score<5) were older, had lower serum albumin and Mini-Mental State
      Examination (MMSE) scores as well as higher overall co-morbidity, prevalence of
      stroke, cancer, and anemia compared to those with intermediate (SPPB=5-8) and
      good physical performance (SPPB=9-12). Fully adjusted multivariate models showed
      that eGFR (modeled as 10 mL/min per 1.73 m(2) intervals) was independently
      associated with the SPPB total score (B=0.49; 95% confidence interval [CI]=0.18
      0.66; p=0.003), balance (B=0.30; 95% CI=0.10-0.49; p=0.005), and muscle strength
      (B=0.06; 95% CI=0.01-0.10; p=0.043), but not with walking speed (B=-0.04; 95% CI=
      0.09-0.11; p=0.107). In conclusion, reduced renal function is associated with
      poorer physical performance in older hospitalized patients. SPPB is worthy of
      testing to monitor changes in physical performance in elderly CKD patients.

PMID- 22950424
TI  - Systems biology and bioinformatics in aging research: a workshop report.
AB  - In an "aging society," health span extension is most important. As in 2010, talks
      in this series of meetings in Rostock-Warnemunde demonstrated that aging is an
      apparently very complex process, where computational work is most useful for
      gaining insights and to find interventions that counter aging and prevent or
      counteract aging-related diseases. The specific topics of this year's meeting
      entitled, "RoSyBA: Rostock Symposium on Systems Biology and Bioinformatics in
      Ageing Research," were primarily related to "Cancer and Aging" and also had a
      focus on work funded by the German Federal Ministry of Education and Research
      (BMBF). The next meeting in the series, scheduled for September 20-21, 2013, will
      focus on the use of ontologies for computational research into aging, stem cells,
      and cancer. Promoting knowledge formalization is also at the core of the set of
      proposed action items concluding this report.

PMID- 22950425
TI  - Quinic acid could be a potential rejuvenating natural compound by improving
      survival of Caenorhabditis elegans under deleterious conditions.
AB  - Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which
      is found to be active in enhancing DNA repair and immunity in model systems and
      able to generate neuroprotective effects in neurons. However, QA's role in
      improving survival is not well studied. Here we report that QA can provide
      protection in Caenorhabidits elegans and improve worm survival under stress.
      Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2)
      survived 17.8% and 29.7% longer, respectively, than the control worms. Our data
      suggest that under heat stress, QA can upregulate the expression of the small
      heat shock protein hsp-16.2 gene, which could help the worms survive a longer
      time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2
      (gk249)] life span by 15.7% under normal culture conditions. However, under
      normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated
      the expression of daf-16 and sod-3 in a DAF-16-dependent manner, and
      downregulated the level of reactive oxygen species (ROS), suggesting that under
      normal conditions QA acts in different pathways. As a natural product, QA
      demonstrates great potential as a rejuvenating compound.

PMID- 22950426
TI  - The challenge of maintaining successful aging at 87 years old: the Octabaix study
      two-year follow-up.
AB  - Preserving physical and cognitive function is crucial to successful aging. The
      objective of this study is to determine how many 87-year-old community-dwelling
      subjects continued to age successfully, according to a definition using a
      quantitative approach, and to assess the predictive value of certain factors
      evaluated 2 years previously. A total of 162 participants were assessed.
      Sociodemographic variables, the Barthel Index (BI), the Spanish version of the
      Mini-Mental State Examination (MEC), the Mini Nutritional Assessment (MNA), the
      Charlson Index, the Gait Rating Scale, social risk, quality of life, prevalent
      chronic diseases, and chronic drug prescription were collected. All subjects with
      scores over 90 points on the BI and above 23 points on the MEC were compared with
      the rest of the participants. A multiple regression analysis was performed. With
      the selected criteria, 90 (61.6%) community-dwelling subjects continued to age
      successfully. The multiple logistic regression analysis showed that the following
      were significantly associated with continued successful aging: A higher level of
      studies (p<0.02, odds ratio [OR] 3.223, 95% confidence interval [CI] 1.158
      8.975), better MEC scores (p<0.01, OR 1.204, 95% CI 1.046-1.386) and Tinetti gait
      scale scores (p<0.01, OR 1.433, 95% CI 1.013-2.027), and fewer chronic drug
      prescriptions (p<0.001, OR 0.768, 95% CI 0.655-0.899). In conclusion, more than
      half of the individuals continued to age successfully. In subjects aged 87 years,
      the factors associated with continued successful aging were longer schooling,
      better cognition scores, lower risk of falls, and fewer chronic drug
      prescriptions at baseline evaluation.

PMID- 22950428
TI  - A score to predict the development of adverse clinical events after transition
      from acute hospital wards to post-acute care settings.
AB  - Adverse clinical events (ACEs) are common in post-acute hospital care. We aimed
      at developing and validating a method, able to be administered in hospital wards,
      for identifying elderly patients at increased risk of ACEs after transferral to
      post-acute care (PAC) facilities. This was a prospective observational study,
      including 502 patients admitted to 19 PAC facilities in northern Italy from July
      1(st) to August 14(th), 2009. A standardized form was used to collect data.
      Variables showing stable association with ACEs in testing group were used to
      derive the score. The relative risk (RR) of developing ACEs according to the
      score was measured in the validation group. Age >=87 years, delirium, pressure
      sore, indwelling bladder catheter, malnutrition, and acute infection on admission
      were identified as stable ACE predictors. A score of 1 was assigned to each
      predictor. Subjects were classified as having low (score=0), medium-low
      (score=1), medium-high (score=2-3), or high (score >=4) risk of ACEs. The RR of
      developing >=1 ACE increased progressively from low (RR=1) to medium-low (RR=1.5,
      95% confidence interval [CI] 1.1-1.9), medium-high (RR=1.6, 95% CI 1.3-2.1), and
      high (RR=1.8, 95% CI 1.4-2.3) risk score. The RR of being not discharged to home
      increased monotonically from 1.0 in low-risk to 2.7 in high-risk groups. In
      conclusion, this study proposes a method, able to be administered in hospital
      wards, for identifying patients at increased risk of ACEs after transferral to
      PAC. The score might also be used to identify people who will not return to home
      after PAC discharge.

PMID- 22950427
TI  - Tissue inhibitor of matrix metalloproteinase-3 or vascular endothelial growth
      factor transfection of aged human mesenchymal stem cells enhances cell therapy
      after myocardial infarction.
AB  - Mesenchymal stem cell (MSC) transplantation has been proposed as a potential
      therapeutic approach for ischemic heart disease, but the regenerative capacity of
      these cells decreases with age. In this study, we genetically engineered old
      human MSCs (O-hMSCs) with tissue inhibitor of matrix metalloproteinase-3 (TIMP3)
      and vascular endothelial growth factor (VEGF) and evaluated the effects on the
      efficacy of cell-based gene therapy in a rat myocardial infarction (MI) model.
      Cultured O-hMSCs were transfected with TIMP3 (O-TIMP3) or VEGF (O-VEGF) and
      compared with young hMSCs (Y-hMSCs) and non-transfected O-hMSCs for growth,
      clonogenic capacity, and differentiation potential. In vivo, rats were subjected
      to left coronary artery ligation with subsequent injection of Y-hMSCs, O-hMSCs, O
      TIMP3, O-VEGF, or medium. Echocardiography was performed prior to and at 1, 2,
      and 4 weeks after MI. Myocardial levels of matrix metalloproteinase-2 (MMP2),
      MMP9, TIMP3, and VEGF were assessed at 1 week. Hemodynamics, morphology, and
      histology were measured at 4 weeks. In vitro, genetically modified O-hMSCs showed
      no changes in growth, colony formation, or multi-differentiation capacity. In
      vivo, transplantation with O-TIMP3, O-VEGF, or Y-hMSCs increased capillary
      density, preserved cardiac function, and reduced infarct size compared to O-hMSCs
      and medium control. O-TIMP3 and O-VEGF transplantation enhanced TIMP3 and VEGF
      expression, respectively, in the treated animals. O-hMSCs genetically modified
      with TIMP3 or VEGF can increase angiogenesis, prevent adverse matrix remodeling,
      and restore cardiac function to a degree similar to Y-hMSCs. This gene-modified
      cell therapy strategy may be a promising clinical treatment to rejuvenate stem
      cells in elderly patients.

PMID- 22950429
TI  - An ideal preparation for dermal regeneration: skin renewal growth factors, the
      growth factor composites from porcine platelets.
AB  - The use of growth factor composites from platelets has been introduced to many
      areas of clinical applications and studies. With the richest source of growth
      factors (GFs), beneficial effects have been shown on tissue regeneration and
      wound healing. However, animal and clinical studies have revealed inconsistent
      outcomes with the use of platelet-derived growth factors (PDGFs), which were
      likely due to variations in the presence and concentrations of GFs between
      various sources. Autologous PDGFs are considered to be safer, but they are
      limited by the feasibility of large-scale production to be used extensively in
      the acute phase, greater surface area, or general cosmetic applications. This
      study employed a simple process to obtain growth factor composites from activated
      platelets of porcine origin, namely skin renewal growth factors (SRGF). The
      functions of SRGF were subsequently evaluated on cultured human fibroblasts,
      keratinocytes, and melanocytes. Our data revealed that SRGF significantly
      promoted the proliferation of fibroblasts, accompanied by increased expression of
      collagens (types I, III, IV, and VIII) and proteoglycans. Diminished
      proliferation and arrested differentiation of keratinocytes were evidenced by the
      attenuated expression of laminin V and keratin 10. In addition, SRGF also
      suppressed the growth of melanocytes and reduced the expression of microphthalmia
      associated transcription factor (MITF), tyrosinase, and paired box 3 (PAX3),
      which mediates melanogensis. Our results suggest that SRGF possesses beneficial
      properties and is a promising and cost-effective composition for the development
      of a safe cosmetic agent or topical products for skin regeneration. The
      development of SRGF may also provide an alternative strategy for tissue
      engineering.

PMID- 22950430
TI  - Estrogen replacement therapy improves pulmonary function in postmenopausal women
      with genital prolapse.
AB  - OBJECTIVE: This study examined the impact of estrogen replacement therapy with
      spirometry on pulmonary function in surgically castrated (salpingo-oophorectomy)
      postmenopausal women with genital prolapse. METHODS: The study included 60
      postmenopausal women with pelvic organ prolapse. The study received institutional
      Ethics Committee approval, and all subjects signed an informed consent. Women
      were randomly divided into two groups of 30 subjects: Group 1 (n=30) was
      administered estrogen replacement with 1 mg of stradiol hemihydrate (1 mg/day)
      orally for 6 months, and group 2 (n=30) was not taking estrogen. Both groups were
      matched by age, height, body mass index, parity, and duration of postmenopause.
      All subjects were evaluated with spirometry initially and after 6 months. For
      statistical analysis, descriptive and analytical methods were used, based on data
      type and distribution. The mean and standard deviations were used as measures of
      central tendency and variability. Categorical data were expressed as absolute and
      relative numbers (percentage). The t-test for independent samples (for comparison
      of groups) and t-test for dependent samples (for comparison of serial
      measurements in the same patients) were used. The analysis was performed using R
      software ( www.r-project.org ), with the level of significance set at p<0.05.
      RESULTS: Analysis of spirometry parameters showed statistically significant
      differences between the estrogen users and the nonusers groups. CONCLUSION: The
      most important study result was the significantly improved lung respiratory
      function in postmenopausal women with genital prolapse after 6 months of taking
      estrogen, confirming that hormone replacement therapy should be recommended to
      postmenopausal women. The findings of our study suggest the need for further
      research into the effect of estrogen on pulmonary function.

PMID- 22950431
TI  - Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related
      dysfunctions in motor coordination and contextual memory in mice: role of
      oxidative stress.
AB  - The aim of this study was to evaluate the effects of olive oil phenols on brain
      aging in mice and to verify whether the antioxidant and antiinflammatory
      activities of these polyphenols were involved. C57Bl/6J mice were fed from middle
      age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in
      phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to
      assess cognitive, motor, and emotional behavior after 6 or 12 months of
      treatment. Parameters of oxidative status and inflammation were measured in
      different brain areas at the same times and evaluated for correlation with
      behavioral changes. The treatment with olive oil phenols improved contextual
      memory in the step-down test to levels similar to young animals and prevented the
      age-related impairment in motor coordination in the rotarod test. This motor
      effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05),
      whereas the memory effect did not correlate with oxidation or inflammation
      parameters. In conclusion, this work points out that natural polyphenols
      contained in extra-virgin olive oil can improve some age-related dysfunctions by
      differentially affecting different brain areas. Such a modulation can be obtained
      with an olive oil intake that is normal in the Mediterranean area, provided that
      the oil has a sufficiently high content of polyphenols.

PMID- 22950432
TI  - Dietary intake of resveratrol enhances the adaptive immunity of aged rats.
AB  - It is well known that immune response declines with aging. Resveratrol, a
      polyphenol that occurs naturally in several plant species including grapevines
      and berries, has been shown to have potent antiaging and health-promoting
      activities. However, the mechanism underlying these activities remains largely
      unknown. Here we clearly demonstrate that: (1) Dietary intake of resveratrol
      induced a significant increase in T helper cells (CD4(+)) in middle-aged (12
      months old) and aged (21 months old) Wistar male rats; (2) resveratrol
      supplementation considerably increased the delayed-type hypersensitivity
      response, a T cell-mediated immune response, in aged rats; and (3) reveratrol
      supplementation remarkably promoted the production of total anti-keyhole limpet
      hemocyanin (KLH) immunoglobulin G (IgG), anti-KLH IgG(1), and anti-KLH
      IgG(2alpha) in aged rats without disturbing immune homeostasis. These data
      together indicate that resveratrol is capable of counteracting immunosenescence,
      thereby leading to rejuvenation. In practice, resveratrol can be useful to help
      the elderly generate an improved response to vaccine with stronger humoral and
      cell-mediated immune responses.

PMID- 22950433
TI  - Potential clinical utility of advanced glycation end product cross-link breakers
      in age- and diabetes-associated disorders.
AB  - Reducing sugars can react nonenzymatically with the amino groups of proteins to
      form Amadori products. These early glycation products undergo further complex
      reactions, such as rearrangement, dehydration, and condensation, to become
      irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced
      glycation end products (AGEs). The formation and accumulation of AGEs have been
      known to progress in a normal aging process and at an accelerated rate under
      diabetes. Nonenzymatic glycation and cross-linking of proteins not only leads to
      an increase in vascular and myocardial stiffness, but also deteriorates
      structural integrity and physiological function of multiple organ systems.
      Furthermore, there is accumulating evidence that interaction of AGEs with a cell
      surface receptor, receptor for AGEs (RAGE), elicits oxidative stress generation
      and subsequently evokes inflammatory, thrombogenic, and fibrotic reactions,
      thereby being involved in atherosclerosis, diabetic microvascular complications,
      erectile dysfunction, and pancreatic beta-cell apoptosis. Recently, AGE cross
      link breakers have been discovered. Therefore, removal of the preexisting AGEs by
      the breakers has emerged as a novel therapeutic approach to various types of
      diseases that develop with aging. This article summarizes the potential clinical
      utility of AGE cross-link breakers in the prevention and management of age- and
      diabetes-associated disorders.

PMID- 22950434
TI  - Spermidine and spermine are enriched in whole blood of nona/centenarians.
AB  - Polyamines (putrescine, spermidine, and spermine) are a family of molecules that
      derive from ornithine through a decarboxylation process. They are essential for
      cell growth and proliferation, stabilization of negative charges of DNA, RNA
      transcription, translation, and apoptosis. Recently, it has been demonstrated
      that exogenously administered spermidine promotes longevity in yeasts, flies,
      worms, and human cultured immune cells. Here, using a cross-sectional
      observational study, we determined whole-blood polyamines levels from 78 sex
      matched unrelated individuals divided into three age groups: Group 1 (31-56
      years, n=26, mean age 44.6+/-6.07), group 2 (60-80 years, n=26, mean age 68.7+/
      6.07), and group 3 (90-106 years, n=26, mean age 96.5+/-4.59). The total content
      of polyamines is significantly lower in groups 2 and 3 compared to group 1
      (p=3.6*10(-12)). Interestingly, this reduction is mainly attributable to the
      lower putrescine content. Group 2 displays the lowest levels of spermidine and
      spermine. On the other hand, nona/centenarians (group 3) display a significantly
      higher median relative percentage content of spermine with respect to total
      polyamines, compared to the other groups (13.2% vs. 14.1% vs. 30.6%, p=6.0*10(
      4)). For the first time, we report profiles of polyamines from the whole blood of
      healthy nona/centenarians, and our results confirm and extend previous findings
      on the role of polyamines in determining human longevity. However, although we
      found an important correlation between polyamines levels and age groups, further
      studies are warranted to fully understand the role of polyamines in determining
      life span. Also, longitudinal and nutritional studies might suggest potential
      therapeutic approaches to sustain healthy aging and to increase human life span.

PMID- 22950435
TI  - Sexing of adults for three Mexican pine cone beetle species, Conophthorus
      conicolens, C. teocotum, and C. michoacanae.
AB  - Individuals belonging to species of the genus Conophthorus (Coleoptera:
      Curculionidae) are notoriously difficult to sex, especially if only certain parts
      of the beetle are available and the genitals are unidentifiable. We are
      presenting evidence demonstrating that rows of setae and setal characteristics at
      the posterior margin of tergite VII (the fifth visible tergite) can be used to
      sex the three Mexican pine cone beetle species Conophthorus conicolens Wood, C.
      teocotum Hopkins, and C. michoacanae Wood, from each other. Although the three
      Conophthorus are clearly described taxonomically by Wood ( 1977 ), the continued
      increase and development of forest plantations with a mixture of host species
      elucidates the importance of having reliable methods of sexing these species for
      purposes of researching and monitoring programs of their populations and pest
      management and control.

PMID- 22950436
TI  - The legal highs problem in the Polish printed media--actors, claims, and its
      hidden meanings.
AB  - The authors present the results of a qualitative analysis of press articles
      focused on legal highs in Poland. The aim of analysis was the identification of
      all social actors involved in the media discourse, the arguments used, and the
      claims made in the frame of social, political, economical, legal, and moral
      issues. This analysis covered two major daily newspapers--Gazeta Wyborcza and
      Rzeczpospolita and two weeklies--Polityka and Newsweek. Articles were collected
      during a systematic analysis covering the complete number of issues starting from
      2008 to 2011. As a result, a base of 386 articles was developed. The study was
      founded by the statutory budget.

PMID- 22950438
TI  - Alcohol use policies that restrict alcohol use.
AB  - The present commentary reacts to ideas including viewing alcohol use as being an
      important device of proper socialization, which may contrast with duties to
      regulate alcohol misuse. I argue that formal policies to restrict alcohol use are
      often based on attempting to reduce misuse of alcohol as an intoxicant, and often
      times support informal policies. In general, evidence-based alcohol misuse
      oriented policies do not intend to greatly restrict nonharmful levels of alcohol
      use.

PMID- 22950437
TI  - Gender differences in the relationship between discrimination and substance use
      disorder among Latinos.
AB  - Using data from the National Latino and Asian American Study collected in 2002
      2003 (N = 2,554), we assessed the adjusted odds of lifetime substance use
      disorder (SUD) associated with report of both unfair treatment and racial/ethnic
      discrimination. Among men, SUD was increased for those reporting low, moderate,
      and high levels of unfair treatment compared to those reporting no unfair
      treatment and patterns were similar for racial/ethnic discrimination. Among
      women, only those reporting high levels of unfair treatment were at increased
      risk of lifetime SUD and no associations were observed between racial/ethnic
      discrimination and lifetime SUD. Future research should examine the role that
      discrimination plays in the development of substance misuse among Latinos.

PMID- 22950439
TI  - Water-dependent reaction pathways: an essential factor for the catalysis in HEPD
      enzyme.
AB  - The hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the critical carbon
      carbon bond cleavage step in the phosphinothricin (PT) biosynthetic pathway. The
      experimental research suggests that water molecules play an important role in the
      catalytic reaction process of HEPD. This work proposes a water involved reaction
      mechanism where water molecules serve as an oxygen source in the generation of
      mononuclear nonheme iron oxo complexes. These molecules can take part in the
      catalytic cycle before the carbon-carbon bond cleavage process. The properties of
      trapped water molecules are also discussed. Meanwhile, water molecules seem to be
      responsible for converting the reactive hydroxyl radical group ((-)OH) to the
      ferric hydroxide (Fe(III)-OH) in a specific way. This converting reaction may
      prevent the enzyme from damages caused by the hydroxyl radical groups. So, water
      molecules may serve as biological catalysts just like the work in the heme enzyme
      P450 StaP. This work could provide a better interpretation on how the
      intermediates interact with water molecules and a further understanding on the
      O(18) label experimental evidence in which only a relatively smaller ratio of
      oxygen atoms in water molecules (~40%) are incorporated into the final product
      HMP.

PMID- 22950440
TI  - Protein capsules assembled via isobutyramide grafts: sequential growth,
      biofunctionalization, and cellular uptake.
AB  - We report the sequential assembly of proteins via the alternating physical
      adsorption of human serum albumin (HSA) and chemical grafting with isobutyramide
      (IBAM) or bromoisobutyramide (BrIBAM) groups. This approach, performed on silica
      template particles, leads to the formation of noncovalent protein films with
      controlled growth at the nanometer scale. Further, after template removal, hollow
      protein capsules with tunable wall thicknesses and high mechanical stability are
      obtained. The use of BrIBAM, compared to IBAM grafts, leads to significantly
      thicker capsule walls, highlighting the influence of the bromine atoms in the
      assembly process, which is discussed in terms of a theoretical model of
      noncovalent interactions. Another feature of the process is the possibility to
      functionalize the HSA capsules with other biologically active macromolecules,
      including enzymes, polysaccharides, or DNA plasmids, demonstrating the
      versatility of this approach. We also report that BrIBAM-HSA and IBAM-HSA
      capsules display negligible cytotoxicity in vitro with HeLa cells and that their
      cellular uptake is dependent on the thickness of the capsule walls. These
      findings support the potential use of these protein capsules in tailored
      biological applications such as drug delivery.

PMID- 22950441
TI  - Safety profile and bleeding risk of ticagrelor compared with clopidogrel.
AB  - INTRODUCTION: Ticagrelor is a novel, non-thienopyridine ADP inhibitor that
      reversibly blocks the P2Y(12) receptor, preventing platelet activation and
      aggregation. It is the first ADP inhibitor to show a mortality benefit in
      patients with acute coronary syndromes (ACS). Its major safety concern, as with
      the other ADP blockers, is bleeding. Other common adverse effects of ticagrelor
      such as dyspnea and ventricular pauses appear to be mild and self-limited. AREAS
      COVERED: The pharmacological properties of ticagrelor compared with clopidogrel
      are explored in this article. In addition, the relevant clinical trials in which
      ticagrelor was investigated are described, with an emphasis on efficacy and
      safety end points. EXPERT OPINION: Although some patients suffer from dyspnea
      when administered with ticagrelor, there is no evidence of any untoward effects
      on the cardiovascular or pulmonary systems. Given that the majority of these
      episodes are mild to moderate and self-limiting, patients should be encouraged to
      continue the medication, as symptoms may resolve. Furthermore, patients with
      underlying heart failure or lung disease do not appear to be at an increased risk
      of developing ticagrelor-induced dyspnea. Its overall mortality benefit among
      patients with ACS, along with its ability to inhibit platelet aggregation more
      rapidly and consistently, makes it the preferred agent over clopidogrel.

PMID- 22950442
TI  - Nanoscale arrangement of proteins by single-molecule cut-and-paste.
AB  - Protein-based nanostructures are key to the organization of life and it is their
      precise arrangement, which determines their specific functions. A single-molecule
      approach for the directed assembly of protein arrangements allows for a
      controlled composition of systems based on protein components. Applying
      antibodies and antigenic peptide tags we utilized the Single-Molecule Cut-and
      Paste (SMC&P) technique for the handling of single proteins. Protein-DNA
      complexes could be arranged to complex patterns with the functionality of the
      protein part remaining unimpaired.

PMID- 22950443
TI  - Organic nanocomposite structure tailored by controlling droplet coalescence
      during inkjet printing.
AB  - Inkjet printing offers a low-cost, high-throughput avenue for producing
      functional organic materials through rapid translation of desktop discoveries to
      industrial roll-to-roll processes. Here, we report a simple, but effective
      strategy to control droplet coalescence during inkjet printing, as a major
      variable, to tailor the nanoscale morphology of organic composite materials
      produced upon evaporation of all-liquid inks. During deposition, the spacing
      between ink droplets was controlled to systematically vary the extent of droplet
      coalescence. Our results show that decreasing coalescence increased the solvent
      evaporation rate, supersaturation of the solutes, and nucleation density of the
      precipitating organic crystals. This phenomenon was utilized to tailor the
      average size of pentaerythritol tetranitrate (PETN) crystals dispersed in an
      adhesive binder matrix from ~0.2 to upwards of 100 MUm. The results suggest that
      controlling the extent of droplet coalescence can be used as an effective means
      to tailor the composite morphology of printed organic materials at the nanoscale.

PMID- 22950444
TI  - 9,10-Diarylanthracenes as stable electrochemiluminescent emitters in water.
AB  - Two hydrophilic diarylanthracenes, explicitly 9,10-bis(N-methylimidazolium-3
      propoxyphenyl)anthracene (DAA1) and 9,10-bis(N-methylimidazolium-3-propoxy-2,6
      dimethylphenyl)anthracene (DAA2), are synthesized and fully characterized. Both
      are found to be soluble in aqueous medium and to exhibit optical properties
      similar to those of the parent 9,10-diphenylanthracene, whose solubility is
      virtually negligible in water. The detailed analysis of their photochemical
      stability as well as electrochemical and electrochemiluminescent properties
      reveals that the sterically highly shielded anthracene DAA2 shows inertness
      toward reactions with singlet oxygen and OH(-) ions during photo- and
      electrochemical initiation and stable ECL emission in aqueous medium.

PMID- 22950445
TI  - Influence of inorganic ions on aggregation and adsorption behaviors of human
      adenovirus.
AB  - In this study, we investigated the influence of inorganic ions on the aggregation
      and deposition (adsorption) behavior of human adenovirus (HAdV). Experiments were
      conducted to determine the surface charge and size of HAdV and viral adsorption
      capacity of sand in different salt conditions. The interfacial potential energy
      was calculated using extended Derjaguin and Landau, Verwey and Overbeek (XDLVO)
      and steric hindrance theories to interpret the experimental results. Results
      showed that different compositions of inorganic ions have minimal effect on
      varying the iso-electric point pH (pH(iep)) of HAdV (ranging from 3.5 to 4.0).
      Divalent cations neutralized/shielded virus surface charge much more effectively
      than monovalent cations at pH above pH(iep). Consequently, at neutral pH the
      presence of divalent cations enhanced the aggregation of HAdV as well as its
      adsorption to sand. Aggregation and adsorption behaviors generally agreed with
      XDLVO theory; however, in the case of minimal electrostatic repulsion, steric
      force by virus' fibers can increase the energy barrier and distance of secondary
      minimum, resulting in limited aggregation and deposition. Overall, our results
      indicated that subsurface water with low hardness residing in sandy soils may
      have a higher potential of being contaminated by HAdV.

PMID- 22950446
TI  - The impact on cardiac diagnosis and mortality of focused transthoracic
      echocardiography in hip fracture surgery patients with increased risk of cardiac
      disease: a retrospective cohort study.
AB  - Hip fracture surgery is associated with a high rate of mortality and morbidity;
      heart disease is the leading cause and is often unrecognised and inadequately
      treated. Pre-operative focused transthoracic echocardiography by anaesthetists
      frequently influences management, but mortality outcome studies have not been
      performed to date. Mortality over the 12 months after hip fracture surgery, in 64
      patients at risk of cardiac disease who received pre-operative echocardiography,
      was compared with 66 randomised historical controls who did not receive
      echocardiography. Mortality was lower in the group that received echocardiography
      over the 30 days (4.7% vs 15.2%, log rank p=0.047) and 12 months after surgery
      (17.1% vs 33.3%, log rank p=0.031). Hazard of death was also reduced with pre
      operative echocardiography over 12 months after adjustment for known risk factors
      (hazard ratio 0.41, 95% CI 0.2-0.85, p=0.016). Pre-operative echocardiography was
      not associated with a delay in surgery. These data support a randomised
      controlled trial to confirm these findings.

PMID- 22950447
TI  - A new horizon of herbal medicines in anorexia-cachexia syndrome.

PMID- 22950448
TI  - Characterization of copper-resistant bacteria and bacterial communities from
      copper-polluted agricultural soils of central Chile.
AB  - BACKGROUND: Copper mining has led to Cu pollution in agricultural soils. In this
      report, the effects of Cu pollution on bacterial communities of agricultural
      soils from Valparaiso region, central Chile, were studied. Denaturing gradient
      gel electrophoresis (DGGE) of the 16S rRNA genes was used for the
      characterization of bacterial communities from Cu-polluted and non-polluted
      soils. Cu-resistant bacterial strains were isolated from Cu-polluted soils and
      characterized. RESULTS: DGGE showed a similar high number of bands and banding
      pattern of the bacterial communities from Cu-polluted and non-polluted soils. The
      presence of copA genes encoding the multi-copper oxidase that confers Cu
      resistance in bacteria was detected by PCR in metagenomic DNA from the three Cu
      polluted soils, but not in the non-polluted soil. The number of Cu-tolerant
      heterotrophic cultivable bacteria was significantly higher in Cu-polluted soils
      than in the non-polluted soil. Ninety two Cu-resistant bacterial strains were
      isolated from three Cu-polluted agricultural soils. Five isolated strains showed
      high resistance to copper (MIC ranged from 3.1 to 4.7 mM) and also resistance to
      other heavy metals. 16S rRNA gene sequence analyses indicate that these isolates
      belong to the genera Sphingomonas, Stenotrophomonas and Arthrobacter. The
      Sphingomonas sp. strains O12, A32 and A55 and Stenotrophomonas sp. C21 possess
      plasmids containing the Cu-resistance copA genes. Arthrobacter sp. O4 possesses
      the copA gene, but plasmids were not detected in this strain. The amino acid
      sequences of CopA from Sphingomonas isolates (O12, A32 and A55), Stenotrophomonas
      strain (C21) and Arthrobacter strain (O4) are closely related to CopA from
      Sphingomonas, Stenotrophomonas and Arthrobacter strains, respectively.
      CONCLUSIONS: This study suggests that bacterial communities of agricultural soils
      from central Chile exposed to long-term Cu-pollution have been adapted by
      acquiring Cu genetic determinants. Five bacterial isolates showed high copper
      resistance and additional resistance to other heavy metals. Detection of copA
      gene in plasmids of four Cu-resistant isolates indicates that mobile genetic
      elements are involved in the spreading of Cu genetic determinants in polluted
      environments.

PMID- 22950450
TI  - Analysis of the pre-retinal opacities in Gaucher Disease using spectral domain
      optical coherent tomography.
AB  - Fundal opacities have been reported in patients with Gaucher disease, a rare
      autosomal recessive lysosomal storage disease, prior to the advent of optical
      coherent tomography. This report provides a detailed analysis of the fundal
      opacities in a 14-year-old girl with genetically proven Gaucher disease using
      spectral domain optical coherent tomography. It illustrates clearly that these
      opacities were pre-retinal opacities located at the vitreo-retinal interface
      associated with localized posterior vitreous detachments, rather than vitreous
      opacities as previously suggested in the literature.

PMID- 22950449
TI  - Partial chromosome 7 duplication with a phenotype mimicking the HOXA1 spectrum
      disorder.
AB  - PURPOSE: To evaluate possible monogenic and chromosomal anomalies in a patient
      with bilateral Duane retraction syndrome and hearing impairment resulting in a
      phenotype resembling the HOXA1 spectrum disorder. METHODS: Sequencing HOXA1 and
      performing high resolution array comparative genomic hybridization (arrayCGH).
      RESULTS: The proband had bilateral Duane retraction syndrome (DRS) with severe
      hearing loss bilaterally and an absent right vertebral artery, mimicking the
      major features of the Bosley-Salih-Alorainy variant of the HOXA1 spectrum.
      However, he also had developmental delay, mild mental retardation, and seizures.
      His parents were not related, but his father had milder sensorineural hearing
      loss bilaterally, and two paternal uncles and a paternal cousin had seizures.
      Neuroimaging revealed moderate maldevelopment of inner ear bony anatomy
      bilaterally. HOXA1 sequencing was normal, but arrayCGH revealed a small partial
      duplication of chromosome 7 encompassing only the PTPRN2 gene (protein tyrosine
      phosphatase, receptor type, N polypeptide 2) that was not present in his parents,
      an unaffected brother, or 53 normal ethnically-matched individuals. CONCLUSIONS:
      PTPRN2 is not yet linked to a genetic syndrome, although its expression has been
      identified in the adult human brain, in certain tumors, and in association with
      type 1 diabetes mellitus. The phenotype of this patient is strikingly similar to,
      but not identical to, that of the HOXA1 spectrum disorder. The findings in this
      patient raise the possibility that PTPRN2 may be active during early development
      of the human brainstem and that its overexpression may cause bilateral DRS with
      hearing loss as occurs in patients with homozygous HOXA1 mutations.

PMID- 22950451
TI  - Human RNA integrity after postmortem retinal tissue recovery.
AB  - PURPOSE: To assess the parameters for postmortem retinal tissue recovery and
      processing that affect the quality of RNA extracted from the retina/retinal
      pigment epithelium (RPE) complex. METHODS: RNA was extracted from retina/RPE
      samples. The RNA quality was determined based on qualitative/quantitative
      measurements made with a Bioanalyzer (Agilent) and on the expression of a long
      retinal gene (RPE65). After a pilot analysis on rats, ocular RNA was extracted
      from human donor eyeballs (group A) explanted according to conventional
      procedures for cornea transplantation. In a second experiment, another group of
      human donor eyeballs (group B) were processed in a much shorter time. The
      postmortem interval (T) comprised two periods: T1, the time between a donor's
      death and enucleation, and T2, the time between eyeball explantation and
      immersion of the excised retina/RPE sample in preservative solution (T = T1 +
      T2). RESULTS: A short T2 was correlated with good quality of RNA extracted from
      the retina/RPE complex (p = 0.043) and successful expression of a tissue-specific
      gene (p = 0.007). No other parameter appeared to influence RNA quality.
      CONCLUSIONS: The time between eyeball explantation and immersion of the
      retina/RPE sample in preservative solution was the chief parameter affecting the
      quality of RNA extracted from the retina/RPE complex.

PMID- 22950452
TI  - Ophthalmic findings in a family with early-onset isolated ectopia lentis and the
      p.Arg62Cys mutation of the fibrillin-1 gene (FBN1).
AB  - PURPOSE: The purpose of this paper is to describe ophthalmic findings in a family
      with isolated ectopia lentis (EL) caused by a specific FBN1 mutation. METHODS:
      Detailed family histories and clinical data were recorded for six isolated EL
      patients of 11 family members. The ophthalmological and systematic examinations
      were performed on patients and unaffected members of the investigated family. The
      detailed ocular examinations included visual acuity, anterior chamber depth,
      pupil size, lens location, optometry, central corneal thickness, keratometry,
      slitlamp examination, fundus examination, axial length, ocular B-ultrasound,
      gonioscope checking, ultrasound biomicroscopy (UBM) and intraocular pressure
      (IOP; Goldmann applanation tonometer). Systematic examinations included the
      measurement of echocardiogram, height, arm span, skull, face, jaw, tooth, breast
      bone, spinal column, and skin. Genomic DNA was extracted using the phenol
      chloroform extraction method for all subjects, and sequencing was carried out on
      an ABI Prism 3730 Genetic Analyzer. RESULTS: A heterozygous mutation, c.184C>T
      (p.Arg62Cys) in exon 2 of FBN1 was identified in all affected members but was not
      found in any unaffected member of the family. Our study presented detailed
      clinical manifestations, including some novel ophthalmic findings, such as
      pupillary abnormality, different types of glaucoma, and progressive hyperopia.
      CONCLUSIONS: Ophthalmic findings and the p.Arg62Cys mutation of FBN1 gene were
      reported in a family with early-onset isolated ectopia lentis.

PMID- 22950453
TI  - Late recurrence of tumor necessitating enucleation in an adult onset
      retinoblastoma.
AB  - Retinoblastoma is the most common primary intraocular malignancy in children.
      Although rare cases of adult onset retinoblastoma have been reported, the numbers
      are very few worldwide. We report a case where tumor recurrence following a
      quiescent period of 31/2 years led to enucleation of the eye in an adult onset
      retinoblastoma. A 33-year-old female was noted to have an intraocular mass lesion
      in the inferonasal quadrant of the retina. Computed Tomography, B-scan and
      vitreous biopsy confirmed the diagnosis of retinoblastoma. The patient underwent
      plaque brachytherapy, cryotherapy, and laser indirect ophthalmoscopy which
      resulted in complete regression of the tumor mass with no areas of activity. At
      the last follow up 31/2 years after the treatment the right eye showed anterior
      chamber infiltration with a tumor-like mass. Fundus examination showed vitreous
      hemorrhage, vitreous seedings and a small focus of tumor reactivation. B-scan,
      ultrasound biomicroscopy and MRI confirmed the mass lesion. In view of the tumor
      infiltrating the anterior chamber and involving the ciliary body prompt
      enucleation of the right eye was performed. The diagnosis of retinoblastoma was
      confirmed by histopathology. It is important that even after complete regression
      of the tumor frequent surveillance with fundus examination is necessary to detect
      early recurrences and to institute prompt management.

PMID- 22950454
TI  - PatA and PatB form a functional heterodimeric ABC multidrug efflux transporter
      responsible for the resistance of Streptococcus pneumoniae to fluoroquinolones.
AB  - All bacterial multidrug ABC transporters have been shown to work as either
      homodimers or heterodimers. Two possibly linked genes, patA and patB from
      Streptococcus pneumococcus, that encode half-ABC transporters have been shown
      previously to be involved in fluoroquinolone resistance. We showed that the
      DeltapatA, DeltapatB, or DeltapatA/DeltapatB mutant strains were more sensitive
      to unstructurally related compounds, i.e., ethidium bromide or fluoroquinolones,
      than the wild-type R6 strain. Inside-out vesicles prepared from Escherichia coli
      expressing PatA and/or PatB transported Hoechst 33342, a classical substrate of
      multidrug transporters, only when both PatA and PatB were coexpressed. This
      transport was inhibited either by orthovanadate or by reserpine, and mutation of
      the conserved Walker A lysine residue of either PatA or PatB fully abrogated
      Hoechst 33342 transport. PatA, PatB, and the PatA/PatB heterodimer were purified
      from detergent-solubilized E. coli membrane preparations. Protein dimers were
      identified in all cases, albeit in different proportions. In contrast to the
      PatA/PatB heterodimers, homodimers of PatA or PatB failed to show a vanadate
      sensitive ATPase activity. Thus, PatA and PatB need to interact together to make
      a functional drug efflux transporter, and they work only as heterodimers.

PMID- 22950455
TI  - Predicting skin penetration of actives from complex cosmetic formulations: an
      evaluation of inter formulation and inter active effects during formulation
      optimization for transdermal delivery.
AB  - Twenty products, containing a radiolabelled form of each active in typical
      cosmetic formulations, were made and applied to female human epidermal membranes
      mounted in Franz diffusion cells for 48 h under 'in use' conditions. The products
      consisted of combinations of five formulations (a hydro-alcoholic gel, an oil in
      water emulsion, a water in oil emulsion, a microemulsion and an oil) with four
      model drug actives (testosterone, hydrocortisone, 5-fluorouracil and
      ketoconazole). Steady-state flux appeared to be reached by 8 h and maintained for
      all products, other than for the microemulsions, consistent with the actives
      being present in the residual formulation on the skin at saturation. The recovery
      for each active at the end of the 48-h study (from a series of stratum corneum
      tape strips, the remaining skin, cumulative amount penetrating into the receptor
      solution, product washed from the skin and on the donor chamber cap) ranged from
      86.5% to 100.6%. The rank order of the fluxes for the actives from the hydro
      alcoholic gel is consistent with the known active molecular size and polarity
      determinants for maximum epidermal flux. Actives with similar steady-state
      (maximum) fluxes from a range of formulations had retention in the stratum
      corneum and similar transport rate constants through the stratum corneum. The
      microemulsion formulation significantly enhanced both the stratum corneum steady
      state flux and transport rate constant for 5-fluorouracil, hydrocortisone and
      testosterone. The penetration flux of each active could be related to its size
      and polarity and appeared maximal when the actives in the different cosmetic
      formulations applied to the skin under 'in use' conditions were likely to remain
      in the residual product on the skin as a saturated solution after solvent
      evaporation. Enhanced penetration fluxes can be achieved by formulation selection
      and an appropriate choice/mix of emollients/adjuvants. The principles described
      here provide a framework for understanding the delivery of cosmetic ingredients
      from various formulations.

PMID- 22950456
TI  - Validity of self-reported use of sulphadoxine-pyrimethamine intermittent
      presumptive treatment during pregnancy (IPTp): a cross-sectional study.
AB  - BACKGROUND: Malaria in pregnancy is a major health problem that can cause
      maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra
      uterine stunting. The WHO recommends use of sulphadoxine-pyrimethamine (SP) for
      intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic
      areas. Towards monitoring and assessing IPTp coverage in the population, the Roll
      Back Malaria Partnership recommends the use of self-reported data. The aim of
      this study was to assess the validity of self-reported IPTp by testing for
      sulphadoxine in maternal blood at delivery. METHODS: Two hundred and four
      pregnant women were consented and enrolled in a cross-sectional study in Mulago
      National Referral Hospital in Kampala Uganda. - Participants who reported a
      history of taking sulpha-containing drugs like co-trimoxazole , those who were
      not sure of dates relating to last menstrual period or who took IPTp within the
      first 20 weeks of gestation were excluded from the study. Data on demographic
      characteristics, obstetric history, and delivery outcome were collected. At
      birth, maternal venous blood was taken off aseptically and used to make thick
      blood smears for malaria parasites and plasma for determining sulphadoxine using
      high performance liquid chromatography (HPLC). RESULTS: Of 120 participants who
      self reported to have used IPTp, 35 (29.2%) tested positive for sulphadoxine by
      HPLC, while 63 (75%) of 84 patients who reported not having used IPTp tested
      negative for sulphadoxine. Participants possessing post-primary education were
      more likely to have reported using IPTp. The low agreement (kappa coefficient =
      0.037) between self-report and actual presence of the drug in the blood casts
      doubt on the validity of self-reported data in estimating IPTp coverage.
      CONCLUSIONS: The results of this study question the accuracy of self-reported
      data in estimating IPTp coverage in the population. More studies on validity of
      self reported data are recommended. Since the validity of IPTp self reports is
      vital for guiding policy on malaria control in pregnancy, ways should be sought
      to improve accuracy of the information from such reports.

PMID- 22950457
TI  - Drug-resistant microorganisms with a higher fitness--can medicines boost
      pathogens?
AB  - Drug-resistant microorganisms (DRMs) are generally thought to suffer from a
      fitness cost associated with their drug-resistant trait, inflicting them a
      disadvantage when the drug pressure reduces. However, Leishmania resistant to
      pentavalent antimonies shows traits of a higher fitness compared to its sensitive
      counterparts. This is likely due the combination of an intracellular pathogen and
      a drug that targets the parasite's general defense mechanisms while at the same
      time stimulating the host's immune system, resulting in a DRM that is better
      adapted to withstand the host's immune response. This review aims to highlight
      how this fitter DRM has emerged and how it might affect the control of
      leishmaniasis. However, this unprecedented example of fitter antimony-resistant
      Leishmania donovani is also of significance for the control of other
      microorganisms, warranting more caution when applying or designing drugs that
      attack their general defense mechanisms or interact with the host's immune
      system. 

PMID- 22950458
TI  - Activities and sources of income after a period of long-term sick leave--a
      population-based prospective cohort study.
AB  - BACKGROUND: There is limited knowledge about what happens to people after long
      term sick leave. The aim of this report was to conduct a prospective study of
      individuals who were on prolonged sick leave during a particular year,
      considering their activities and sources of income during subsequent years. To
      enable comparison of different time periods, we used three cohorts of individuals
      with different starting years. METHODS: Using data from national registers, three
      separate cohorts were constructed that included all people living in Sweden who
      were 20-64 years of age (>5 million) in the years 1995, 2000 and 2005,
      respectively. The individual members of the cohorts were classified into the
      following groups based on their main source of income and activity in 1995-2008:
      on long-term sick leave, employed, old-age pensioner, long-term unemployed,
      disability pensioner, on parental leave, social assistance recipient, student
      allowance recipient, deceased, or emigrated. RESULTS: Most individuals on long
      term (> 6 months) sick leave in 1995 were not employed 13 years later. Only 11%
      of the women and 13% of the men were primarily in employment after 13 years.
      Instead, a wide range of alternatives existed, for example, many had been granted
      disability pension, and about 10% of the women and 17% of the men had died during
      the follow-up period. A larger proportion of those with long-term sick leave were
      back in employment when 2005 was the starting year for the follow-up.
      CONCLUSIONS: The low future employment rates for people on long-term sick leave
      may seem surprising. There are several possible explanations for the finding: The
      disorders these people may have, might have entailed longstanding difficulties on
      the labor market. Besides, long-term absence from work, no matter what its causes
      were, might have worsen the chances of further employment. The economic cycles
      may also have been of importance. The improving labor market during later years
      seems to have improved the chances for employment among those earlier on long
      term sick leave.

PMID- 22950459
TI  - The microRNA miR-181c controls microglia-mediated neuronal apoptosis by
      suppressing tumor necrosis factor.
AB  - BACKGROUND: Post-ischemic microglial activation may contribute to neuronal damage
      through the release of large amounts of pro-inflammatory cytokines and neurotoxic
      factors. The involvement of microRNAs (miRNAs) in the pathogenesis of disorders
      related to the brain and central nervous system has been previously studied, but
      it remains unknown whether the production of pro-inflammatory cytokines is
      regulated by miRNAs. METHODS: BV-2 and primary rat microglial cells were
      activated by exposure to oxygen-glucose deprivation (OGD). Global cerebral
      ischemia was induced using the four-vessel occlusion (4-VO) model in rats.
      Induction of pro-inflammatory and neurotoxic factors, such as tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO), were assessed
      by ELISA, immunofluorescence, and the Griess assay, respectively. The miRNA
      expression profiles of OGD-activated BV-2 cells were subsequently compared with
      the profiles of resting cells in a miRNA microarray. BV-2 and primary rat
      microglial cells were transfected with miR-181c to evaluate its effects on TNF
      alpha production after OGD. In addition, a luciferase reporter assay was
      conducted to confirm whether TNF-alpha is a direct target of miR-181c. RESULTS:
      OGD induced BV-2 microglial activation in vitro, as indicated by the
      overproduction of TNF-alpha, IL-1beta, and NO. Global cerebral
      ischemia/reperfusion injury induced microglial activation and the release of pro
      inflammatory cytokines in the hippocampus. OGD also downregulated miR-181c
      expression and upregulated TNF-alpha expression. Overproduction of TNF-alpha
      after OGD-induced microglial activation provoked neuronal apoptosis, whereas the
      ectopic expression of miR-181c partially protected neurons from cell death caused
      by OGD-activated microglia. RNAinterference-mediated knockdown of TNF-alpha
      phenocopied the effect of miR-181c-mediated neuronal protection, whereas
      overexpression of TNF-alpha blocked the miR-181c-dependent suppression of
      apoptosis. Further studies showed that miR-181c could directly target the 3'
      untranslated region of TNF-alpha mRNA, suppressing its mRNA and protein
      expression. CONCLUSIONS: Our data suggest a potential role for miR-181c in the
      regulation of TNF-alpha expression after ischemia/hypoxia and microglia-mediated
      neuronal injury.

PMID- 22950460
TI  - Identities in the third space? Solidity, elasticity and resilience amongst young
      British Pakistani Muslims.
AB  - Over the last decade the issue of identity has been prevalent in discussions
      about British Muslims, with the events of 9/11 serving as a touchstone for media
      debates about religious, national and cultural affiliations. The 7/7 terrorist
      attacks in the UK led to young British Pakistanis being subjected to intense
      public and institutional scrutiny and wider political concerns being expressed
      about the failure of multiculturalism. Young British Pakistanis have thus had to
      negotiate and maintain their identities in an environment in which they have been
      defined as a threat to national security whilst simultaneously being pressurized
      to align with 'core British values'. Within this context, we convey the findings
      of a qualitative study involving British Pakistanis living in the North-west of
      England. In presenting the experiences and perspectives of participants, three
      interconnected processes salient to the maintenance of identity are delineated:
      solidity, elasticity and resilience. Having unpacked these processes, we draw
      upon Bhabha's third space thesis to explore the political potentiality of and the
      limits to hybridic identities.

PMID- 22950461
TI  - Self-interest and the theory of action.
AB  - The concept of self-interest remains underdeveloped in sociology although central
      to economics. Recent methodological and social trends render sociological
      indifference to the concept untenable. The term has enjoyed historical
      predominance in the West since the sixteenth century. While it is seen in modern
      economics as a singular motivating force, Adam Smith regarded self-interest in
      economic action as necessarily moderated by sympathy. In addition to its
      problematic economic conceptualization self-interest has an experiential basis in
      unequal power relations. An alternative to the concept of self-interest is
      presented by Amartya Sen in his account of commitment; its inconsistencies,
      however, render Sen's statement unsatisfactory. Differences between present and
      future interests indicate that the distinction between self-interested and other
      interested action is not sustainable.

PMID- 22950462
TI  - On natural-social commodities. The form and value of things.
AB  - This article re-reads Marx's account of the commodity as a socio-natural entity.
      In doing so, it re-evaluates the status of the political (as opposed to questions
      of political economy) in Marx's analysis and also reads his argument in light of
      Actor-Network-Theory's call for the thingness of things to be taken seriously.
      The paper argues that there is a complex duality to the commodity as it is always
      comprised of both use-value and exchange-value and hence as both 'natural' and
      'social'. It is pointed out that the usual translation of words with the root
      'gesellschaft-' as 'social' is unhelpful and that a better term would be
      'societal', as this enables Marx, and us, to re-approach the very distinction
      between the natural, the societal and the social. Marx's notion of 'value as
      equivalence' is then outlined and it is argued that this crucial stage in his
      account is often passed over. Value as equivalence is not a mere social
      production but relies upon the expression of the use-value of one thing in
      another. This leads to the third move which is an outline of the importance of
      value-form and social form. It is argued that it is this formation of a commodity
      (comprising both the natural and the social) which is the key both to
      understanding it as a specific historical entity as well as offering a powerful,
      non-reductive, account of the natural, social, material and historical character
      of things. Overall, the article attempts to develop a novel conception of natural
      social commodities which does not premise either side of this dyad and so might
      help social theorists to talk of real things whilst avoiding charges of
      essentialism and reductionism as well as possible Latourian critiques of over
      generalization.

PMID- 22950463
TI  - Class, gender and time poverty: a time-use analysis of British workers' free time
      resources.
AB  - Free time, that is, the time that remains at one's own discretion after
      conducting daily work and personal care activities, has been previously
      recognized as a 'primary good' and an important welfare resource that provides
      opportunities for participation in social life and leisure. However, recent years
      have witnessed an increasing preoccupation with the phenomenon of time poverty,
      drawing attention to the distribution of free time and its relationship to
      structural and family circumstances. In this article we propose a novel approach
      to the measurement of time poverty and document its occurrence amongst British
      workers. In line with previous literature, a conceptualization of time poverty as
      a relative lack of free time resources vis-a-vis other members of the community
      is adopted. However, unlike previous empirical studies, we investigate the
      differential configuration of time poverty on weekdays and weekend days,
      alongside indicators of the quality of free time, taking into account insights
      from theoretical and empirical work within the field of the sociology of time.
      Our analysis of the 2000 UK Time Use Survey highlights class and gender
      inequalities that have been missed by previous measurement approaches and
      demonstrates that, overall, working women experience multiple and more severe
      free time constraints, which may constitute an additional barrier for their
      leisure and social participation.

PMID- 22950464
TI  - Struggles for value: value practices, injustice, judgment, affect and the idea of
      class.
AB  - This paper is about the struggle for value by those who live intensified
      devaluation in the new conditions of legitimation and self-formation, by which
      the self is required to repeatedly reveal its value through its accrual and
      investment in economic, symbolic, social and cultural capitals. It explores how
      this value struggle is experienced: felt affectively, known and spoken through
      discourses of injustice. Drawing on a small research project, which uses the
      British New Labour government's Respect Agenda as an evocative device to provoke
      discussion, the paper details how those positioned as already marginal to the
      dominant symbolic, presented as 'useless' subjects rather than 'subjects of
      value' of the nation, generate alternative ways for making value. It examines how
      the experience of injustice generates affective responses expressed as 'ugly
      feelings'. The conversion of these 'ugly feelings' into articulations of 'just
      talk' reveals how different understandings of value, of what matters and what
      counts, come into effect and circulate alongside the dominant symbolic. The issue
      that most angered working-class respondents is how they are positioned, judged,
      blamed and held responsible for an inheritance over which they have no control,
      'an accident of birth'. They were acutely aware of how they were constantly
      judged and de-legitimated and how practices such as selfishness and greed were
      legitimate for others. Showing how they refuse to authorize those they consider
      lacking in value but with authority and in a position to judge, the paper
      demonstrates how class relations are lived through a struggle, not only against
      economic limitation but a struggle against unjustifiable judgment and authority
      and for dignified relationality. The paper reveals a struggle at the very core of
      ontology, demonstrating how the denigrated defend and make their lives liveable;
      an issue at the heart of current austerity politics which may have increased
      significance for the future.

PMID- 22950465
TI  - Desperately seeking social approval: Adam Smith, Thorstein Veblen and the moral
      limits of capitalist culture.
AB  - Adam Smith and Thorstein Veblen shared much in matters of economic ontology. Both
      dismissed the very notion of an autonomous economic self and instead investigated
      the processes through which self and other are mutually constituted under
      changing cultural traditions of individual aspiration. Their strikingly similar
      critiques of status-oriented consumption and concern for the moral basis of the
      market economy are established in this manner. However, the political
      implications of their analyses point in different directions, with Veblen being
      the more radical. The Smithian individual can always use spectatorial insights to
      assert through genuinely praiseworthy behaviour personal moral distance from
      social norms of status-oriented consumption. The Veblenian individual, by
      contrast, has no such capacity for elevating abstract moral principles above
      socially-situated conduct, as mind and environment co-evolve in line with
      changing material circumstances of life. For Veblen, the rise of status-oriented
      consumption itself acted as a form of moral self-education that more deeply
      entrenched the social norms of ownership out of which it arose, thus the
      impossibility of an autonomous economic self was matched by the impossibility of
      an autonomous moral self. To his way of thinking, moral degradation in
      conspicuous consumption was irredeemably inscribed into the whole cultural
      structure of capitalism.

PMID- 22950466
TI  - Devalued, deskilled and diversified: explaining the proliferation of the strip
      industry in the UK.
AB  - This paper looks beyond the debates that focus on the objectification of the
      female body to examine the question as to why strip clubs have proliferated and
      found a permanent place in the night-time economy in the UK. Using empirical
      qualitative and quantitative data from the largest study into the strip industry
      in the UK to date, we challenge the common assumption that 'demand' is
      responsible for the rise in erotic dance. Instead, we argue that the
      proliferation of strip clubs is largely due to the internal economic structures
      of the industry which have developed partly in response to the financial crisis
      beginning in 2008. First, we argue that clubs profit from individual dancers
      through an exploitative system of fees and fines, rendering a strip club business
      a low cost investment with high returns and little risk to club owners. Second,
      we note that the last decade has seen diversification of the industry accompanied
      by deskilling and devaluing of dancing and dancers' labour. Third, we demonstrate
      that despite the negative effects of these changes on workers, there has been an
      expansion of the industry as the ability to make profit, even during a financial
      crisis was ensured through the transferral of risk to workers. Overall, we
      suggest that far from proliferating as a response to demand, the industry has
      maintained its market presence due to its ability to establish highly financially
      exploitation employment relationships with dancers at a time of economic
      fragility.

PMID- 22950467
TI  - The logic of strategic ignorance.
AB  - Ignorance and knowledge are often thought of as opposite phenomena. Knowledge is
      seen as a source of power, and ignorance as a barrier to consolidating authority
      in political and corporate arenas. This article disputes this, exploring the ways
      that ignorance serves as a productive asset, helping individuals and institutions
      to command resources, deny liability in the aftermath of crises, and to assert
      expertise in the face of unpredictable outcomes. Through a focus on the Food and
      Drug Administration's licensing of Ketek, an antibiotic drug manufactured by
      Sanofi-Aventis and linked to liver failure, I suggest that in drug regulation,
      different actors, from physicians to regulators to manufacturers, often battle
      over who can attest to the least knowledge of the efficacy and safety of
      different drugs - a finding that raises new insights about the value of ignorance
      as an organizational resource.

PMID- 22950468
TI  - Patronage and secularization: social obligation and church support.
AB  - As a contribution to our understanding of secularization in Britain, this paper
      examines the role of religious patronage. It illustrates nineteenth and early
      twentieth century support for the churches from rural landowners and major
      industrial employers, considers its benefits, and explains its rapid
      disappearance. The paper argues that the end of the expectation that high status
      individuals and major employers would actively promote organized religion is both
      significant evidence of secularization and a cause of further decline.

PMID- 22950469
TI  - Highly sensitive ratiometric fluorescent chemosensor for silver ion and silver
      nanoparticles in aqueous solution.
AB  - A pyrene derivative chemosensor (Pyr-WH) based on a dipeptide shows a highly
      sensitive ratiometric response to Ag(I) as well as silver nanoparticles in
      aqueous solution at physiological pH. Pyr-WH penetrated live HeLa cells and
      exhibits a ratiometric response to intracellular Ag(I). The binding mode of Pyr
      WH with Ag(I) was characterized based on fluorescence changes in different pH,
      NMR, and ESI mass spectrometer experiments.

PMID- 22950471
TI  - Trends in health worker performance after implementing the Integrated Management
      of Childhood Illness strategy in Benin.
AB  - OBJECTIVE: Training health workers to use Integrated Management of Childhood
      Illness (IMCI) guidelines can improve care for ill children in outpatient
      settings in developing countries. However, even after IMCI training, important
      performance gaps exist. One potential reason is that the effect of training can
      rapidly wane. Our aim was to determine if the performance of IMCI-trained health
      workers deteriorated over 3 years. METHODS: We studied two departments in Benin.
      First, we performed a record review of 32 IMCI-trained health workers during the
      first year of IMCI implementation (2001-2002). Second, we analysed data from
      cross-sectional health facility surveys from 2001 to 2004 that represented the
      entire study area. Primary outcomes were the proportion of children under 5 years
      old with potentially life-threatening illnesses who received either recommended
      or adequate treatment, and among all children, an index of overall guideline
      adherence. Secondary outcomes reflected the treatment of individual diseases.
      Outcomes were calculated monthly, and time trends were evaluated with regression
      modelling. RESULTS: The record review included 9393 consultations, and the
      surveys included 411 consultations performed by 105 health workers. For both data
      sources, performance trends were essentially flat for nearly all outcomes.
      Absolute levels of performance revealed substantial performance gaps.
      CONCLUSIONS: We found no evidence that performance declined over 3 years after
      IMCI training. However, important performance gaps found immediately after IMCI
      training persisted and should be addressed.

PMID- 22950472
TI  - Molecular mobility in dense protein systems: an investigation through 1H NMR
      relaxometry and diffusometry.
AB  - Understanding how proteins behave in highly concentrated systems is a major issue
      in many fields of research, including biology, biophysics, and chemical
      engineering. In this paper, we provide a comprehensive (1)H NMR study of
      molecular mobility in dilute to highly concentrated dispersions of the exact same
      protein (casein) but organized in two distinct supramolecular forms: spongelike
      casein micelles or soft casein aggregates. Both relaxometry and diffusometry
      experiments were performed, so that three different parameters are reported: spin
      spin relaxation rates of non-water protons (1/T(2,ne)), spin-spin relaxation
      rates of water protons (1/T(2,e+w)), and water self-diffusion coefficients
      (D(w)). The results are discussed in an effort to understand the respective
      effects of protein crowding and protein supramolecular organization on each
      mobility indicator. We also examine if connections exist between the observed
      changes in molecular mobility and the already documented changes in rheological
      and osmotic properties of casein dispersions as concentration is increased.

PMID- 22950473
TI  - Raft formation by the red imported fire ant, Solenopsis invicta.
AB  - The raft behavior of the invasive red imported fire ant, Solenopsis invicta Buren
      (Hymenoptera: Formicidae), has been documented for over a century. However, no
      rigorous tests have been performed elucidating the structure, limits, and
      important characteristics of this behavior. Rafting makes S. invicta competitive
      in both native and foreign environments. Further understanding of this behavior
      will provide critical advancement to the comprehension of this ant's global
      invasion ecology. Though speculations exist, no one has looked at the movements
      of individuals within the raft formation, the longevity of rafts, raft success
      rate, or the importance of different life stages and varying types of adults to
      raft formation. Furthermore, bubble use has been extensively studied in
      arthropods, but it has never been documented in social insects. The use of
      bubbles as a means of floatation has never before been noted in raft formation.
      This study shows that ants trapped under water escape by lifting themselves to
      the air-water interface through the use of bubbles collected from submerged
      substrate. The presence of larvae was noted to increase colony survival and
      maximize raft longevity due in part their ability to hold bubbles under
      hydrophobic setae.

PMID- 22950475
TI  - Removal of Cu(II) and fulvic acid by graphene oxide nanosheets decorated with
      Fe3O4 nanoparticles.
AB  - Graphene oxide/Fe(3)O(4) (GO/Fe(3)O(4)) composites were synthesized and
      characterized by scanning electron microscopy, transmission electron microscopy,
      and X-ray photoelectron spectroscopy. The removal of Cu(II) and a natural organic
      macromolecule (fulvic acid (FA)) by GO/Fe(3)O(4) was investigated. The mutual
      effects of FA/Cu(II) on Cu(II) and FA sorption onto GO/Fe(3)O(4), as well as the
      effect of pH, ionic strength, FA/Cu(II) concentrations, and the addition
      sequences of FA/Cu(II) were examined. The results indicated that Cu(II) sorption
      on GO/Fe(3)O(4) were strongly dependent on pH and independent of ionic strength,
      indicating that the sorption was mainly dominated by inner-sphere surface
      complexation rather than outer-sphere surface complexation or ion exchange. The
      presence of FA leads to a strong increase in Cu(II) sorption at low pH and a
      decrease at high pH, whereas the presence of Cu(II) led to an increase in FA
      sorption. The adsorbed FA contributes to the modification of sorbent surface
      properties and partial complexation of Cu(II) with FA adsorbed. Different effects
      of FA/Cu(II) concentrations and addition sequences on Cu(II) and FA sorption were
      observed, indicating the difference in sorption mechanisms. After GO/Fe(3)O(4)
      adsorbed FA, the sorption capacity for Cu(II) was enhanced at pH 5.3, and the
      sorption capacity for FA was also enhanced after Cu(II) sorption on GO/Fe(3)O(4).
      These results are important for estimating and optimizing the removal of metal
      ions and organic substances by GO/Fe(3)O(4) composites.

PMID- 22950476
TI  - EPR investigation of zinc/iodine exchange between propargyl iodides and
      diethylzinc: detection of propargyl radical by spin trapping.
AB  - The production of propargyl radicals in the reaction of dialkylzincs with
      propargyl iodides in nondegassed medium was investigated by EPR using tri-tert
      butylnitrosobenzene (TTBNB) as a spin trap. The radical mechanism and the nature
      of the observed species were confirmed by the trapping of propargyl radicals
      generated by an alternative pathway: i.e., upon irradiation of propargyl iodides
      in the presence of hexa-n-butyldistannane. In dialkylzinc-mediated experiments a
      high concentration of adduct was instantaneously observed, whereas no spontaneous
      production of spin adduct was detected in a blank experiment performed with the
      propargylic iodide and TTBNB in the absence of diethylzinc. Under irradiation in
      the presence of distannane, two different species were observed at the very
      beginning of the irradiation; the nitroxide resulting from the trapping of
      propargyl radical at the propargyl carbon remained the only species detected
      after irradiating for several minutes. The absence of adducts resulting from the
      trapping of allenyl canonical forms was supported by DFT calculations and by the
      preparation of an authentic sample.

PMID- 22950477
TI  - Influence of the calcination and carbonation conditions on the CO2 uptake of
      synthetic Ca-based CO2 sorbents.
AB  - In this work we report the development of a Ca-based, Al(2)O(3)-stabilized
      sorbent using a sol-gel technique. The CO(2) uptake of the synthetic materials as
      a function of carbonation and calcination temperature and CO(2) partial pressure
      was critically assessed. In addition, performing the carbonation and calcination
      reactions in a gas-fluidized bed allowed the attrition characteristics of the new
      material to be investigated. After 30 cycles of calcination and carbonation
      conducted in a fluidized bed, the CO(2) uptake of the best sorbent was 0.31 g
      CO(2)/g sorbent, which is 60% higher than that measured for Rheinkalk limestone.
      A detailed characterization of the morphology of the sol-gel derived material
      confirmed that the nanostructure of the synthetic material is responsible for its
      high, cyclic CO(2) uptake. The sol-gel method ensured that Ca(2+) and Al(3+) were
      homogenously mixed (mostly in the form of the mixed oxide mayenite). The
      formation of a finely and homogeneously dispersed, high Tammann temperature
      support stabilized the nanostructured morphology over multiple reaction cycles,
      whereas limestone lost its initial nanostructured morphology rapidly due to its
      intrinsic lack of a support component.

PMID- 22950478
TI  - Photoelectrochemical and impedance spectroscopic investigation of water oxidation
      with "Co-Pi"-coated hematite electrodes.
AB  - Uniform thin films of hematite (alpha-Fe(2)O(3)) deposited by atomic layer
      deposition (ALD) coated with varying amounts of the cobalt phosphate catalyst,
      "Co-Pi," were investigated with steady-state and transient photoelectrochemical
      measurements and impedance spectroscopy. Systematic studies as a function of Co
      Pi thickness were performed in order to clarify the mechanism by which Co-Pi
      enhances the water-splitting performance of hematite electrodes. It was found
      that under illumination, the Co-Pi catalyst can efficiently collect and store
      photogenerated holes from the hematite electrode. This charge separation reduces
      surface state recombination which results in increased water oxidation
      efficiency. It was also found that thicker Co-Pi films produced increased water
      oxidation efficiencies which is attributed to a combination of superior charge
      separation and increased surface area of the porous catalytic film. These
      combined results provide important new understanding of the enhancement and
      limitations of the Co-Pi catalyst coupled with semiconductor electrodes for water
      splitting applications.

PMID- 22950479
TI  - The Manchester Color Wheel: validation in secondary school pupils.
AB  - BACKGROUND: As part of our research programme into facilitating improved ways of
      communicating with patients, especially about more sensitive clinical issues, we
      have been investigating whether there are any non-verbal methods that might aid
      this process. One such approach is to ask patients to choose a color in response
      to a particular question, for instance about health or psychological status, and
      for this purpose we developed the Manchester Color Wheel (MCW). This instrument
      consists of positive, neutral and negative colors and its validation in normal
      adults and those with anxiety or depression showed that it is responsive to
      change and reproducible. It also has the capacity to identify a positive frame of
      mind. We concluded that it might be a particularly useful instrument in
      adolescents and therefore this study aimed to validate it in a secondary school.
      METHODS: 620 pupils (aged 11-17 years, mean age 14.0 years, 298 (48.1%) males,
      322 (51.9%) females) at Sale Grammar School in Greater Manchester were asked to
      relate their mood to a MCW color and also complete the Hospital Anxiety
      Depression (HAD) questionnaire. To give these pupils an experience in science,
      197 were divided into four subgroups for an 'experiment' to ascertain whether,
      compared to controls, a change in mood color choice could be induced by
      participation in sport, music or art activities. RESULTS: Although mood color and
      HAD depression score are unlikely to be measuring exactly the same psychological
      state, a negative mood color was chosen by 62.5% of HAD depressed compared to
      only 14.5% of HAD normal pupils (p < 0.001). In contrast, a positive mood color
      was chosen by 48.9% of normal and only 18.8% of depressed pupils (p < 0.001). In
      the 'experiment', compared to controls, all activities resulted in an increased
      choice of positive mood colors which reached significance for sport and music.
      CONCLUSION: This study confirms the potential utility of the MCW to rapidly and
      easily assess a variety of health issues in large populations, including
      adolescents. Some of our results should also be of interest to educationalists.

PMID- 22950480
TI  - Are salt loading and prolonging infusion period effective in prevention of
      amphotericin B-induced nephrotoxicity?
AB  - INTRODUCTION: Nephrotoxicity is generally considered as the most clinically
      significant adverse reaction of amphotericin B, and has been reported in up to
      80% of amphotericin B recipients during the first 2 weeks of treatment. Numerous
      experimental and clinical investigations have been performed over the past 4
      decades, to find appropriate interventions for preventing or minimizing the
      nephrotoxic effects of amphotericin B. AREAS COVERED: The aim of this literature
      review was to collect available clinical data regarding interventions to prevent
      amphotericin B-induced nephrotoxicity in human populations. A literature search
      was performed in the following databases: Scopus, Medline, Embase, Cochrane
      central register of controlled trials, and Cochrane database systematic reviews.
      The key words used as search terms were 'amphotericin', 'amphotericin B',
      'nephrotoxicity', 'renal failure', 'renal damage', 'renal dysfunction', 'renal
      impairment', 'prevention', 'preventive measures', and 'preventive interventions'.
      EXPERT OPINION: Studies in humans have clearly demonstrated that salt loading can
      prevent or alleviate an amphotericin B-induced rise in serum creatinine, or
      decrease in glomerular filtration rate, without beneficial effects on tubular
      toxicity of amphotericin B. Current clinical data regarding the prolongation of
      amphotericin B duration of infusion in the prevention of nephrotoxicity is
      controversial and associated with several clinical and practical drawbacks.

PMID- 22950481
TI  - Good function after shoulder arthroplasty.
AB  - BACKGROUND AND PURPOSE: Different results after shoulder arthroplasty have been
      found for different diagnostic groups. We evaluated function, pain, and quality
      of life after shoulder arthroplasty in 4 diagnostic groups. PATIENTS AND METHODS:
      Patients with shoulder arthroplasties registered in the Norwegian Arthroplasty
      Register from 1994 through 2008 were posted a questionnaire in 2010. 1,107
      patients with rheumatoid arthritis (RA), osteoarthritis (OA), acute fracture
      (AF), or fracture sequela (FS) returned completed forms (65% response rate). The
      primary outcome measure was the Oxford shoulder score (OSS), which assesses
      symptoms and function experienced by the patient on a scale from 0 to 48. A
      secondary outcome measure was the EQ-5D, which assesses life quality. The
      patients completed a questionnaire concerning symptoms 1 month before surgery,
      and another concerning the month before they received the questionnaire. RESULTS:
      Patients with RA and OA had the best results with a mean improvement in OSS of 16
      units, as opposed to 11 for FS patients. Both shoulder pain and function had
      improved substantially. The change in OSS for patients with AF was negative (
      11), but similar end results were obtained for AF patients as for RA and OA
      patients. Quality of life had improved in patients with RA, OA, and FS.
      INTERPRETATION: Good results in terms of pain relief and improved level of
      function were obtained after shoulder arthroplasty for patients with RA, OA, and
      to a lesser degree-FS. A shoulder arthropathy had a major effect on quality of
      life, and treatment with shoulder replacement substantially improved it.

PMID- 22950482
TI  - Phosphatidylinositol 4,5-biphosphate (PIP(2)) lipids regulate the phosphorylation
      of syntaxin N-terminus by modulating both its position and local structure.
AB  - Syntaxin (STX) is a N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) protein that binds to the plasma membrane and regulates ion channels and
      neurotransmitter transporters. Experiments have established the involvement of
      the N-terminal segment of STX in direct protein-protein interactions and have
      suggested a critical role for the phosphorylation of serine 14 (S14) by casein
      kinase-2 (CK2). Because the organization of STX in the plasma membrane was shown
      to be regulated by phosphatidylinositol 4,5-biphosphate (PIP(2)) lipids, we
      investigated the mechanistic involvement of PIP(2) lipids in modulating both the
      membrane interaction and the phosphorylation of STX, using a computational
      strategy that integrates mesoscale continuum modeling of protein-membrane
      interactions, with all-atom molecular dynamics (MD) simulations. Iterative
      applications of this protocol produced quantitative evaluations of lipid-type
      demixing due to the protein and identified conformational differences between STX
      immersed in PIP(2)-containing and PIP(2)-depleted membranes. Specific sites in
      STX were identified to be important for the electrostatic interactions with the
      PIP(2) lipids attracted to the protein, and the segregation of PIP(2) lipids near
      the protein is shown to have a dramatic effect on the positioning of the STX N
      terminal segment with respect to the membrane/water interface. This PIP(2)
      dependent repositioning is shown to modulate the extent of exposure of S14 to
      large reagents representing the CK2 enzyme and hence the propensity for
      phosphorylation. The prediction of STX sites involved in such PIP(2)-dependent
      regulation of STX phosphorylation at S14 offers experimentally testable probes of
      the mechanisms and models presented in this study, through structural
      modifications that can modulate the effects.

PMID- 22950483
TI  - The role of chelants in controlling Cu(II)-induced radical chemistry in oxidative
      hair colouring products.
AB  - The catalytic formation of hydroxyl radicals in oxidative hair colourant systems
      in the presence of added copper ions was measured and quantified using a
      colorimetric probe N,N'-(5-nitro-1,3-phenylene)bisglutaramide. Also monitored in
      the same experiments was the decomposition of hydrogen peroxide. The first set of
      experiments was performed using aqueous model solutions containing the key
      oxidant actives in a hair colourant, ammonium hydroxide and hydrogen peroxide at
      pH 10, with added copper and calcium ions. The second set of experiments was
      performed in the presence of hair containing different levels of copper in
      conditions very close to those found during hair colouring. Both sets of
      experiments demonstrate the ability of copper ions to trigger the formation of
      hydroxyl radicals and catalyse the decomposition of hydrogen peroxide. The
      ability of chelants ethylenediamine tetraacetic acid (EDTA) and N,N'
      ethylenediamine disuccinic acid (EDDS) to moderate the flux of hydroxyl radicals
      formed in solution systems was demonstrated in the presence of copper ions alone.
      However, only EDDS was successful in the presence of both calcium and copper
      ions. This was confirmed in the hair experiments where again only EDDS was
      successful at preventing hydroxyl radical formation where hair is added as the
      source of copper and calcium ions. These results are explained using metal
      speciation modelling and demonstrate the importance of the chelant to be able to
      specifically bind and prevent the one-electron redox chemistry of copper in the
      presence of high levels of calcium ions as found in hair. The formation of
      hydroxyl radicals during the colouring process was shown to lead to hair
      structure damage as measured by protein loss. EDDS was demonstrated to
      significantly reduce cuticle damage by suppressing the formation of the hydroxyl
      radicals in systems with realistic concentrations of calcium and copper.

PMID- 22950484
TI  - A randomised comparison of two intranasal dexmedetomidine doses for premedication
      in children.
AB  - We compared sedation levels in children following administration of intranasal
      dexmedetomidine. One hundred and sixteen children aged between 1 and 8 years were
      enrolled in this prospective, randomised trial. Children were assigned to receive
      either intranasal dexmedetomidine 1 MUg.kg(-1) (Group 1) or 2 MUg.kg(-1) (Group
      2). Thirty-one (53%) patients from Group 1 and 38 (66%) patients from Group 2
      were satisfactorily sedated at the time of anaesthetic induction. Logistic
      regression showed a significant interaction effect (p=0.049), with the odds ratio
      between Group 2 over Group 1 estimated as 1.1 (95% CI 0.5-2.7) for the 1-4 year
      age group, and 10.5 (95% CI 1.4-80.2) for the 5-8 year age group. Both doses
      produced a similar level of satisfactory sedation in children aged 1-4 years,
      whereas 2 MUg.kg(-1) resulted in a higher proportion of satisfactory sedation in
      children aged 5-8 years. There were no adverse haemodynamic effects. We conclude
      that intranasal dexmedetomidine in a premedication dose of 2 MUg.kg(-1) resulted
      in excellent sedation in children.

PMID- 22950485
TI  - Investigation of noise-induced instabilities in quantitative biological
      spectroscopy and its implications for noninvasive glucose monitoring.
AB  - Over the past decade, optical spectroscopy has been employed in combination with
      multivariate chemometric models to investigate a wide variety of diseases and
      pathological conditions, primarily due to its excellent chemical specificity and
      lack of sample preparation requirements. Despite promising results in several
      proof-of-concept studies, its translation to the clinical setting has often been
      hindered by inadequate accuracy of the conventional spectroscopic models. To
      address this issue and the possibility of curved (nonlinear) effects in the
      relationship between the concentrations of the analyte of interest and the
      mixture spectra (due to fluctuations in sample and environmental conditions),
      support vector machine-based least-squares nonlinear regression (LS-SVR) has been
      recently proposed. In this paper, we investigate the robustness of this
      methodology to noise-induced instabilities and present an analytical formula for
      estimating modeling precision as a function of measurement noise and model
      parameters. This formalism can be readily used to evaluate uncertainty in
      information extracted from spectroscopic measurements, particularly important for
      rapid-acquisition biomedical applications. Subsequently, using field data (Raman
      spectra) acquired from a glucose clamping study on an animal model subject, we
      perform the first systematic investigation of the relative effect of additive
      interference components (namely, noise in prediction spectra, calibration
      spectra, and calibration concentrations) on the prediction error of nonlinear
      spectroscopic models. Our results show that the LS-SVR method gives more accurate
      results and is substantially more robust to additive noise when compared with
      conventional regression methods such as partial least-squares regression (PLS),
      when careful selection of the LS-SVR model parameters are performed. We
      anticipate that these results will be useful for uncertainty estimation in
      similar biomedical applications where the precision of measurements and its
      response to noise in the data set is as important, if not more so, than the
      generic accuracy level.

PMID- 22950486
TI  - Using classification tree modelling to investigate drug prescription practices at
      health facilities in rural Tanzania.
AB  - BACKGROUND: Drug prescription practices depend on several factors related to the
      patient, health worker and health facilities. A better understanding of the
      factors influencing prescription patterns is essential to develop strategies to
      mitigate the negative consequences associated with poor practices in both the
      public and private sectors. METHODS: A cross-sectional study was conducted in
      rural Tanzania among patients attending health facilities, and health workers.
      Patients, health workers and health facilities-related factors with the potential
      to influence drug prescription patterns were used to build a model of key
      predictors. Standard data mining methodology of classification tree analysis was
      used to define the importance of the different factors on prescription patterns.
      RESULTS: This analysis included 1,470 patients and 71 health workers practicing
      in 30 health facilities. Patients were mostly treated in dispensaries. Twenty two
      variables were used to construct two classification tree models: one for
      polypharmacy (prescription of >=3 drugs) on a single clinic visit and one for co
      prescription of artemether-lumefantrine (AL) with antibiotics. The most important
      predictor of polypharmacy was the diagnosis of several illnesses. Polypharmacy
      was also associated with little or no supervision of the health workers,
      administration of AL and private facilities. Co-prescription of AL with
      antibiotics was more frequent in children under five years of age and the other
      important predictors were transmission season, mode of diagnosis and the location
      of the health facility. CONCLUSION: Standard data mining methodology is an easy
      to-implement analytical approach that can be useful for decision-making.
      Polypharmacy is mainly due to the diagnosis of multiple illnesses.

PMID- 22950488
TI  - Factors associated with HIV testing and condom use in Mozambique: implications
      for programs.
AB  - BACKGROUND: To identify predictors of HIV testing and condom use in Mozambique.
      METHODS: Nationally representative survey data collected in Mozambique in 2009
      was analyzed. Logistic regression analysis was used for two outcomes: HIV testing
      and condom use. RESULTS: Women at a higher risk of HIV were less likely to be
      tested for HIV than women at a lower risk: compared to married women, HIV testing
      was lower among never married women (OR = 0.37, CI: 0.25-0.54); compared to women
      with one lifetime partner, HIV testing was lower among women with four or more
      lifetime partners (OR = 0.62, CI: 0.47-0.83). Large wealth differentials were
      observed: compared to the poorest women, HIV testing was higher among the
      wealthiest women (OR = 3.03, CI: 1.96-4.68). Perceived quality of health services
      was an important predictor of HIV testing: HIV testing was higher among women who
      rated health services as being of very good quality (OR = 2.12, CI: 1.49-3.00).
      Type of sexual partner was the strongest predictor of condom use: condom use was
      higher among men who reported last sex with a girlfriend (OR = 9.75, CI: 6.81
      13.97) or a casual partner (OR = 11.05, CI: 7.21-16.94). Being tested for HIV
      during the last two years was the only programmatic variable that predicted
      condom use. Interestingly, being tested for HIV more than two years ago was not
      associated with condom use. Frequent mass media exposure was neither associated
      with HIV testing nor with condom use. CONCLUSIONS: The focus of HIV testing
      should shift from married women (routinely tested during antenatal care visits)
      to unmarried women and women with multiple sexual partners. Financial barriers to
      HIV testing appear to be substantial. Since HIV testing is done without a fee
      being charged, these barriers are presumably related to the cost of
      transportation to static health facilities. Mechanisms should be developed to
      cover the cost of transportation to health facilities. Substantially increasing
      community-based counseling is one way of reducing the cost of transportation. Men
      should be encouraged to test for HIV periodically.

PMID- 22950487
TI  - Nighttime assaults: using a national emergency department monitoring system to
      predict occurrence, target prevention and plan services.
AB  - BACKGROUND: Emergency department (ED) data have the potential to provide critical
      intelligence on when violence is most likely to occur and the characteristics of
      those who suffer the greatest health impacts. We use a national experimental ED
      monitoring system to examine how it could target violence prevention
      interventions towards at risk communities and optimise acute responses to
      calendar, holiday and other celebration-related changes in nighttime assaults.
      METHODS: A cross-sectional examination of nighttime assault presentations (6.01
      pm to 6.00 am; n = 330,172) over a three-year period (31st March 2008 to 30th
      March 2011) to English EDs analysing changes by weekday, month, holidays, major
      sporting events, and demographics of those presenting. RESULTS: Males are at
      greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95%
      confidence intervals [CIs] 3.11-3.16; P < 0.001); with male:female ratios
      increasing on more violent nights. Risks peak at age 18 years. Deprived
      individuals have greater risks of presenting across all ages (AOR 3.87, 95% CIs
      3.82-3.92; P < 0.001). Proportions of assaults from deprived communities increase
      midweek. Female presentations in affluent areas peak aged 20 years. By age 13,
      females from deprived communities exceed this peak. Presentations peak on Friday
      and Saturday nights and the eves of public holidays; the largest peak is on New
      Year's Eve. Assaults increase over summer with a nadir in January. Impacts of
      annual celebrations without holidays vary. Some (Halloween, Guy Fawkes and St
      Patrick's nights) see increased assaults while others (St George's and
      Valentine's Day nights) do not. Home nation World Cup football matches are
      associated with nearly a three times increase in midweek assault presentation.
      Other football and rugby events examined show no impact. The 2008 Olympics saw
      assaults fall. The overall calendar model strongly predicts observed
      presentations (R2 = 0.918; P < 0.001). CONCLUSIONS: To date, the role of ED data
      has focused on helping target nightlife police activity. Its utility is much
      greater; capable of targeting and evaluating multi-agency life course approaches
      to violence prevention and optimising frontline resources. National ED data are
      critical for fully engaging health services in the prevention of violence.

PMID- 22950489
TI  - Further findings linking SSRIs during pregnancy and persistent pulmonary
      hypertension of the newborn: clinical implications.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a rare but potentially
      life-threatening neonatal condition. Several authors have suggested that late
      pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) may
      increase the risk of PPHN. This association has been investigated in seven
      published studies that have shown mixed findings based on diverse methods.
      Several methodological limitations may account for the diversity of findings,
      which include, in some studies, a lack of control for well established risk
      factors for PPHN. The methodological improvement in the most recent study
      tentatively suggests that infants prenatally exposed to SSRIs are approximately
      twice as likely to suffer PPHN. Further research on the biological mechanisms
      involved is required. Clinicians should consider late pregnancy exposure to SSRIs
      as one of several possible risks for PPHN, which has implications for both
      prescribing SSRIs to pregnant women and for neonatal care of SSRI-exposed
      infants.

PMID- 22950491
TI  - Alteplase: a review of its use in the management of acute ischaemic stroke.
AB  - Alteplase (Actilyse((r)), Activase((r))) is a recombinant tissue-type plasminogen
      activator that activates plasminogen directly to plasmin. It is the only
      pharmacological treatment currently approved for patients with acute ischaemic
      stroke. This article reviews the efficacy and tolerability of alteplase, focusing
      on data relevant to treatment between 0 and 4.5 hours after onset of stroke, and
      summarizes its pharmacological properties. Well designed clinical trials showed
      that alteplase administered within 3 hours (in the NINDS trial) and between 3 and
      4.5 hours (in the ECASS III trial) after stroke onset significantly improved
      clinical outcomes at 90 days relative to placebo. Alteplase was generally well
      tolerated in these trials, with no significant difference observed between
      alteplase and placebo recipients in the 90-day mortality rates, despite
      significantly higher incidences of any and symptomatic intracranial haemorrhages
      in alteplase recipients. These results were generally supported by those of the
      SITS-MOST and SITS-ISTR observational studies, which showed that alteplase was
      effective and generally well tolerated when administered within 4.5 hours of
      stroke onset in routine clinical practice. However, results from SITS-ISTR
      indicated that the safety and functional outcomes were generally less favourable
      when alteplase was administered 3-4.5 hours after stroke onset than within 3
      hours of stroke onset. Additionally, results from pooled analyses of randomized
      clinical trials indicated that the benefit of alteplase therapy over placebo
      decreased as the time between stroke onset and treatment initiation increased,
      with no significant benefit observed when treatment was initiated >4.5 hours
      after stroke onset. Moreover, the odds of mortality increased as the time between
      stroke onset and treatment initiation increased. Thus, the greatest benefit of
      alteplase therapy is gained with early treatment. Based on these results, current
      EU labelling and treatment guidelines recommend that alteplase should be
      administered as early as possible within 4.5 hours of symptom onset in patients
      with acute ischaemic stroke. However, recent results from a meta-analysis and IST
      3 suggest that some patients may benefit from treatment up to 6 hours after
      stroke onset. Patients for whom alteplase therapy is contraindicated as per
      current EU licensing criteria, such as those aged >80 years, may also benefit
      from therapy. Further randomized trials of alteplase administered >4.5 hours
      after stroke in selected patients are required to confirm these findings.

PMID- 22950492
TI  - Sulforaphane protects small intestinal mucosa from aspirin/NSAID-induced injury
      by enhancing host defense systems against oxidative stress and by inhibiting
      mucosal invasion of anaerobic enterobacteria.
AB  - BACKGROUND AND AIMS: Recent studies have shown that daily use of NSAIDs,
      frequently causes small intestinal ulcers and erosions. However, effective drugs
      to prevent aspirin/NSAIDs-induced small intestinal lesions have not been
      developed. In the present study, we examined the effects of sulforaphane (SFN), a
      substance rich in broccoli sprouts, on aspirin/NSAIDs-induced small intestinal
      injury. METHODS: 1. In vitro study: IEC6 cells, derived from rat small intestinal
      mucosae, were incubated with or without SFN. The cells were subsequently exposed
      to aspirin. In some experiments, the effect of zinc protoporphyrin-IX (ZnPP), 0.1
      MUM, an inhibitor of heme oxygenase- 1 (HO-1), was also examined. 2. In vivo
      study: IND-induced small intestinal mucosal injury was induced in male ddY mice.
      SFN glucosinolates (SGS), which is glucosinolates precursor of SFN, was orally
      administered to the mice, at dose of 17 mg/mouse, before and after the injection
      of IND. Vascular permeability was assessed by measuring the amount of exudated
      Evans Blue in the mucosa, which had been injected intravenously. Neutrophil
      activation was evaluated by myeloperoxidase (MPO) activity. Amount of mucosal
      anaerobic bacteria was also measured. RESULTS: 1. In vitro study: (1) SFN, 5 MUM,
      significantly attenuated aspirin (20 mM)-induced cell injury. (2) SFN enhanced HO
      1 expression in IEC-6 cells. The protective effect of SFN against aspirin-induced
      injury was attenuated by 0.1 MUM ZnPP. 2. In vivo study: (1) IND treatment caused
      mucosal injury in small intestine, increased vascular permeability, enhanced MPO
      activity, and augmented mucosal invasion of anaerobic enterobacteria. (2) SGS
      attenuated the IND-induced small intestinal injury. (3) SGS prevented the IND
      induced increase in mucosal invasion of anaerobic enterobacteria. CONCLUSIONS:
      These results suggest that SFN protects small intestine from aspirin / NSAIDs
      induced injury, presumably by up-regulating nrf2-keap1 dependent antioxidant
      system and by inhibiting invasion of anaerobic bacteria into the mucosa.

PMID- 22950493
TI  - Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms
      of gastroprotective and ulcer healing actions of antacids.
AB  - This article updates current views on gastric mucosal defense, injury, protection
      and ulcer healing with a focus on mucosal protective and ulcer healing actions of
      antacids. The gastric mucosa is continuously exposed to a variety of noxious
      factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids,
      lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others.
      Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post
      epithelial defense mechanisms permitting the mucosa to withstand exposure to the
      above damaging factors. When mucosal defense is weakened or overwhelmed by
      injurious factors, injury develops in the form of erosions or ulcers. In the late
      1970s Andre Robert and coworkers discovered that microgram amounts of a
      prostaglandin E2 analog protects the gastric mucosa against a variety of
      ulcerogenic and necrotizing agents - even such strong inducers of injury as 100%
      ethanol and boiling water. They proposed a new concept of cytoprotection.
      Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal
      growth factor were shown to exert protective action on gastric mucosa.
      Additionally, some antacids have been shown to exert a potent mucosal protective
      action against a variety of injurious factors and accelerate healing of erosions
      and gastric ulcers. These actions of antacids, especially hydrotalcite - the
      newest and the most extensively studied antacid - are due to activation of
      prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H.
      pylori toxins; induction of heat shock proteins; and, activation of genes
      encoding growth factors and their receptors.

PMID- 22950490
TI  - Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and
      management.
AB  - Frontotemporal lobar degeneration (FTLD) describes a spectrum of clinically,
      pathologically and genetically heterogeneous neurodegenerative disorders of
      unknown aetiology. FTLD spectrum disorders collectively represent a leading cause
      of early-onset dementia, with most cases presenting between 45 and 64 years of
      age. FTLD is characterized by progressive changes in behaviour, executive
      dysfunction and/or language impairment and can be differentiated clinically into
      three frontotemporal dementia (FTD) syndromes as follows: (i) behavioural variant
      (bvFTD); (ii) semantic dementia (SD); and (iii) progressive nonfluent aphasia
      (PNFA). Additionally, there is a significant clinical, pathological and genetic
      overlap between FTD and motor neuron disease/amyotrophic lateral sclerosis (FTD
      ALS) and the atypical parkinsonian syndromes, progressive supranuclear palsy
      (PSP) and corticobasal syndrome (CBS). bvFTD is characterized by progressive
      behavioural impairment and a decline in executive function with frontal lobe
      predominant atrophy, SD by a loss of object knowledge with prominent anomia and
      asymmetrical atrophy of the anterior temporal lobes and PNFA by expressive or
      motor speech deficits with predominantly left peri-sylvian atrophy. Recent
      advances in molecular biology and immunohistochemical staining techniques have
      further classified the FTLD spectrum disorders based upon the predominant
      neuropathological protein into three main categories: (i) microtubule-associated
      protein tau (FTLD-TAU); (ii) TAR DNA-binding protein-43 (FTLD-TDP); and (iii)
      fused in sarcoma protein (FTLD-FUS). Up to 40% of FTD patients report a family
      history of neurodegenerative illness, and one-third to one-half of familial cases
      of FTD follow an autosomal dominant inheritance pattern. Mutations in MAPT, PGRN,
      TARDBP, VCP and CHMP2B have been described, along with a recently identified
      C9ORF72 hexanucleotide repeat expansion. To date, there are no US FDA-approved
      treatments or disease-modifying therapies for FTD. Pharmacological strategies
      have focused on neurotransmitter replacement and modulation for the treatment of
      behavioural, motor and cognitive symptoms of FTD, and include selective serotonin
      reuptake inhibitors (SSRIs), atypical antipsychotics, acetylcholinesterase
      inhibitors and glutamate NMDA receptor antagonists. At present, adequate
      management of FTD symptoms involves a combination of pharmacological therapy with
      behavioural, physical and environmental modification techniques.

PMID- 22950494
TI  - Chemoprevention of cancers in gastrointestinal tract with cyclooxygenase 2
      inhibitors.
AB  - The finding that cyclooxygenase-2 (COX-2) is over-expressed and plays an
      important role in carcinogenesis in gastrointestinal (GI) cancers including
      esophagus, gastric and colorectal cancers has triggered the researches of COX-2
      inhibitors as the chemopreventive option for GI cancers. This reviewer updates
      the current molecular biology on the regulation of COX-2 expression,
      pharmacological concepts of COX-2 inhibitors in the chemoprevention of GI tract,
      the clinical efficacies of COX -2 inhibitors in prevention of cancers in GI tract
      and associated main adverse events. In inflammation, COX-2 expression is
      regulated both at the transcriptional and posttranscriptional levels.
      Hypermethylation of the CpG island in the COX-2 gene is the major cause of COX-2
      silencing in a subset of GI cancers. However, the tumor-inhibitory efficacy of
      non-selective non-steroidal antiinflammatory drugs (NSAIDs) or selective COX-2
      inhibitors is not necessarily related to their COX-inhibitory potential. These
      compounds harbor additional pharmacological activities that are entirely
      independent of its COX-2 inhibitory activity. The clearly identified targets
      relevant for anticancer therapy, the benefits from clinical chemoprevention of GI
      tract cancers and the absence of adverse findings of cardiovascular function or
      histopathology in preclinical toxicology studies indicate the promising results
      of COX-2 inhibitors. The efficacy and toxicity of NSAIDs are a consequence of the
      inhibition of the COX enzymes. Therefore, an optimal regime of COX-2 inhibitors
      in chemoprevention of GI cancers should be further investigated probably by
      adjustment of dosage, duration, integration of co-therapy and careful selection
      of candidates.

PMID- 22950495
TI  - Novel possible pharmaceutical research tools: stem cells, gene delivery and their
      combination.
AB  - Both stem cell research and gene delivery are very promising fields of today's
      biomedical research. In the present review we first attempt to summarize the
      state of the art in stem cell research. We describe the major categories of stem
      cells based on cell sources: embryonic, fetal, postnatal and induced pluripotent
      stem cells. We then present new data on stem cell cultures of dental pulp origin
      as examples of the progress of postnatal stem cell research. Afterwards, we
      briefly summarize the most promising achievements in the field of gene delivery.
      As an example of such advances, we describe novel in vitro and in vivo gene
      delivery studies to demonstrate that salivary glands are highly potential targets
      for gene therapy: they can be used to produce therapeutic peptides delivered
      either into the oral cavity or into the systemic circulation. Finally, we
      describe and compare studies combining the use of stem cells and gene delivery.
      We conclude that stem cell therapy and gene delivery alone are both very exciting
      research areas, and they may act in synergy when used in combination.

PMID- 22950496
TI  - Discovery of lansoprazole and its unique pharmacological properties independent
      from anti-secretory activity.
AB  - The proton pump inhibitors (PPIs) lansoprazole (LPZ) and omeprazole (OPZ) have
      been widely used for more than 20 years in the treatment of acid-related diseases
      such as gastro-duodenal ulcers and reflux esophagitis. Both LPZ and OPZ are
      derivatives of 2-[(2- pyridylmethyl)sulfinyl]-1H-benzimidazole, but LPZ has a
      trifluoroethoxy group in the molecule which seems to provide unique
      pharmacological properties in addition to its anti-secretory effect. For example,
      the anti-secretory effect of LPZ in rats was roughly 2 times greater than that of
      OPZ but the anti-ulcer effects were more than 10 times stronger than those of OPZ
      in rat models of reflux esophagitis, indomethacin-induced gastric antral ulcers
      and mepirizole-induced duodenal ulcers. It has also been reported that LPZ has
      acid-independent protective effects on the gastrointestinal mucosa, anti
      inflammatory effects, and anti-bacterial effects on Helicobacter pylori. In
      contrast, recent advances in endoscopy have revealed that non-steroidal anti
      inflammatory drugs (NSAIDs) often cause ulcers not only in the stomach and
      duodenum, but also in the small intestine in humans. Anti-secretory drugs such as
      PPIs and histamine H(2)-receptor antagonists (H(2)-RAs) are commonly used for the
      treatment of upper gastrointestinal mucosal lesions induced by NSAIDs. However,
      the effects of these drugs on NSAID-induced small intestinal lesions are still
      not fully understood. In this article, both a brief history of the discovery of
      LPZ and the unique pharmacological properties of LPZ independent from its anti
      secretory action are reviewed, and the effects of PPIs and H(2)-RAs on NSAID
      induced small intestinal lesions are discussed.

PMID- 22950498
TI  - Taming the irritable bowel.
AB  - This narrative review covers the mechanisms of actions of trendy drugs approved
      for or proposed for calming the irritable bowel. Many drugs that target
      functional gastrointestinal disorders (FGIDS), which includes IBS, have their
      actions in the enteric nervous system (i.e., the brain-in-the-gut). The in-depth
      insight into fundamental neurophysiology, which is essential for understanding
      how the drugs act to achieve their effects, is covered from a
      neurogastroenterological view point. Pharmacotherapeutic research in FGIDS, which
      is now lagging, is focused mainly on symptom control. Major progress will require
      a change to orientation on the malfunction underlying each of the symptoms that
      constitute Manning, Rome I and Rome II symptom-based criteria for FIGD diagnoses.
      A high incidence of autoimmune degenerative neuropathy in the enteric nervous
      system occurs in IBS and is postulated to be the cause of symptoms emerging from
      failure of normal neural control of motility, blood flow and secretory glands, in
      concert with sensitization of spinal and vagal sensory mechanisms.

PMID- 22950497
TI  - Antimicrobial peptides and colitis.
AB  - Antimicrobial peptides (AMPs) are important components of innate immunity. They
      are often expressed in response to colonic inflammation and infection. Over the
      last several years, the roles of several antimicrobial peptides have been
      explored. Gene expression of many AMPs (beta defensin HBD2-4 and cathelicidin) is
      induced in response to invasion of gut microbes into the mucosal barrier. Some
      AMPs are expressed in a constitutive manner (alpha defensin HD 5-6 and beta
      defensin HBD1), while others (defensin and bactericidal/ permeability increasing
      protein BPI) are particularly associated with Inflammatory Bowel Disease (IBD)
      due to altered defensin expression or development of autoantibodies against
      Bactericidal/permeability increasing protein (BPI). Various AMPs have different
      spectrum and strength of antimicrobial effects. Some may play important roles in
      modulating the colitis (cathelicidin) while others (lactoferrin, hepcidin) may
      represent biomarkers of disease activity. The use of AMPs for therapeutic
      purposes is still at an early stage of development. A few natural AMPs were shown
      to be able to modulate colitis when delivered intravenously or intracolonically
      (cathelicidin, elafin and SLPI) in mouse colitis models. New AMPs (synthetic or
      artificial non-human peptides) are being developed and may represent new
      therapeutic approaches against colitis. This review discusses the latest research
      developments in the AMP field with emphasis in innate immunity and
      pathophysiology of colitis.

PMID- 22950499
TI  - Target-oriented mechanisms of novel herbal therapeutics in the chemotherapy of
      gastrointestinal cancer and inflammation.
AB  - A prominent group of effective cancer chemopreventive drugs has been derived from
      natural products having low toxicity while possessing apparent benefit in the
      disease process. It is plausible that there are multiple target molecules
      critical to cancer cell survival. Herbal terpenoids have demonstrated excellent
      target-specific anti-neoplastic functions by suppression of cell proliferation
      and induction of apoptosis. Transcriptional molecules in the NF-kappaB, MEK/ERK
      and PI3K/Akt/mTOR pathways are important molecular targets of chemotherapy that
      play distinctive roles in modulating the apoptosis cascades. It is recently
      suggested that NSAID-activated gene (NAG-1), a novel proapoptotic protein, is the
      upstream anti-carcinogenic target of NSAIDs, PPAR ligands and herbal
      chemotherapeutic agents that triggers some of the events mentioned above.
      Besides, angiogenesis, oxidative stress as well as inflammation are important
      factors that contribute to the development and metastasis of cancer, which could
      be actively modulated by novel agents of plant origin. The aim of the present
      review is to discuss and summarize the contemporary use of herbal therapeutics
      and phytochemicals in the treatment of human cancers, in particular that of the
      colon. The major events and signaling pathways in the carcinogenesis process
      being potentially modulated by natural products and novel herbal compounds will
      be evaluated, with emphasis on some terpenoids. Advances in eliciting the precise
      cellular and molecular mechanisms during the anti-tumorigenic process of novel
      herbal therapeutics will be of imperative clinical significance to increase the
      efficacy and reduce prominent adverse drug effects in cancer patients through
      target-specific therapy.

PMID- 22950500
TI  - Role of nitric oxide in the central interferon-alpha-induced inhibition of
      gastric acid secretion in rats.
AB  - Cytokines are known to play a key role in regulation of gastric functions.
      Interferon-alpha (IFN-alpha) has been published to impair gastric motility. Aims
      of this study were to clarify effect of IFN-alpha on gastric acid secretion (GAS)
      and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000,
      10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections
      of IFN-alpha dose-dependently inhibited GAS induced by pylorus ligation in male
      SD rats in 2 hrs (370+/-40, 233+/-39, 208+/-50 micromol vs control 415+/-59
      micromol and 481+/-50, 249+/-75, 141+/-25 micromol vs control 485+/-65 micromol,
      respectively). Central doses inducing same level inhibition were 100 times lower.
      NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50)
      dose 100 IU IFN-alpha (507+/-75 micromol/2 hrs), while L-arginine, the substrate
      of nitric oxide synthase (NOS) prevented L-NAME action (266+/-82 micromol/2 hrs).
      D-arginine failed to prevent L-NAME action on IFN-alpha-induced inhibition of
      GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to
      block IFN-alpha induced inhibition of GAS. Results suggest that IFN-alpha
      inhibits GAS centrally through nitric oxide pathways probably mediated by
      continuous isoform of NOS that can be important in regulation of GAS in healthy
      or pathological conditions.

PMID- 22950501
TI  - Gastric mucosal protection and central nervous system.
AB  - Several human and experimental data suggest the particular importance of gastric
      protective processes in maintaining mucosal integrity. Both peripheral and
      central mechanisms are involved in this process. In the periphery, pre-epithelial
      mucus-bicarbonate layer, mucus, phospholipids, trefoil peptides, prostaglandins,
      heat shock proteins, sensory neuropeptides, nitric oxide, and hydrogen sulfide
      may mediate mucosal protection. In the central nervous system hypothalamus and
      dorsal vagal complex (DVC) have particular important role in the regulation of
      centrally-induced gastroprotection. Stimulation of paraventricular nuclei either
      aggravates or inhibits the mucosal injury depending on the ulcer model. Vagal
      nerve also has a dual role, its activation can induce mucosal injury (by high
      dose of thyrotropin- releasing hormone (TRH), electrical stimulation), however,
      integrity of vagal nerve is necessary for gastroprotection induced either
      peripherally (by PGE2, prostacyclin, adaptive cytoprotection), or centrally (e.g.
      by neuropeptides). The centrally induced gastroprotection is likely to be vagal
      dependent, though vagal independent pathways have also been shown. Endomorphin-1
      and endomorphin-2, selective MU-opioid receptor ligands, proved to be highly
      potent and effective gastroprotective agents in ethanol ulcer model (0.03-3 pmol
      intracerebroventricularly). Inhibition of the degradation of endomorphins by
      diprotin A resulted in gastroprotective effect, indicating the potential role of
      these endogenous opioids in the regulation of gastric mucosal integrity.
      Endomorphin-2 injected intracerebroventricularly restored the reduced levels of
      CGRP and somatostatin in gastric mucosa induced by ethanol. In conclusion,
      neuropeptides expressed in dorsal vagal complex and hypothalamus may have a
      regulatory role in maintaining gastric mucosal integrity by stimulating the
      formation of mucosal protective compounds.

PMID- 22950502
TI  - Irsogladine: overview of the mechanisms of mucosal protective and healing-
      promoting actions in the gastrointestinal tract.
AB  - Irsogladine, a mucosal protective drug, was developed in Japan for the treatment
      of peptic ulcer disease and acute gastritis. This drug is superior to gefarnate,
      the same therapeutic category drug, in a randomized, controlled and double-blind
      clinical study in 1987. The mechanisms of irsogladine's actions are apparently
      different from those of antisecretory drugs. Irsogladine increases intracellular
      cyclic adenosine 3',5'-monophosphate content via non-selective inhibition of
      phosphodiesterase isozymes and exhibits gastric cytoprotection partly mediated by
      endogenous nitric oxide. These effects may account for a variety of actions of
      irsogladine in the gastrointestinal tract, including facilitation of gap
      junctional intercellular communication, inhibition of the reduced gastric mucosal
      blood flow response, suppression of reactive oxygen generation and so on. Since
      1984, more than 60 papers have been published to further verify the effects of
      irsogladine on gap junctional intercellular communication, tight junction, nitric
      oxide production and neutrophil migration as well as Helicobacter pylori-related
      pathological changes in the stomach as well as the adverse reactions induced in
      the stomach or the small intestine by various drugs, including nonsteroidal anti
      inflammatory drugs, bisphosphonates or selective serotonin re-uptake inhibitors.
      In this article, we review recent advances in understanding the mechanisms of
      irsogladine's actions and the most recent data in experimental as well as
      clinical studies.

PMID- 22950503
TI  - Gastroprotective role of glucocorticoids during NSAID-induced gastropathy.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) make significant contributions to
      gastric ulcer disease which remains widespread. Although several factors have
      been postulated as pathogenic elements of the gastric injury induced by NSAIDs,
      it is, however believed that prostaglandin deficiency plays a critical role in
      the pathogenesis of this injury. During prostaglandin deficiency, other defensive
      mechanisms might operate to attenuate NSAID-induced gastropathy. According to our
      results, NSAIDs, similar to stress, induce an increase in glucocorticoid
      production that in turn helps the gastric mucosa to resist the harmful actions of
      these drugs. In this article, we review our experimental data suggesting that
      glucocorticoids may play a role as natural defensive factors in maintaining the
      integrity of the gastric mucosa during NSAID therapy and might operate to
      attenuate NSAID-induced gastropathy.

PMID- 22950504
TI  - Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157.
AB  - Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent,
      proven in clinical trials to be both safe in inflammatory bowel disease (PL-10,
      PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no
      toxicity being reported. Recently, we claim that BPC 157 may be used as an
      antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach,
      duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain,
      hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel
      function, counteraction of prolonged bleeding and thrombocytopenia after
      application of various anticoagulants and antiplatelet agents and wound healing
      improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC
      157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC
      157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract,
      liver and brain and finally, counteraction of aspirin-induced prolonged bleeding
      and thrombocytopenia) obviously have a counteracting effect on several
      established side-effects of NSAIDs use. The mentioned variety of the beneficial
      effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as
      a NSAIDs antidote since no other single agent has portrayed a similar array of
      effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be
      not achieved)) profile is reported for BPC 157. Also, unlike the different dosage
      levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten,
      all these beneficial and counteracting effects of BPC 157 were obtained using the
      equipotent dosage (MUg, ng/kg) in parenteral or peroral regimens.

PMID- 22950505
TI  - Novel pharmacologic approaches to the prevention and treatment of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the
      colonic mucosa followed by poor quality of healing and recurring lesions. Recent
      studies demonstrated that the poor healing and chronic inflammation in colon of
      UC could be the result of microvascular dysfunction and endothelial barrier
      defect, resulting in sustained tissue hypoperfusion and ischemia in the colon.
      Long before angiogenesis became a popular research topic, our laboratory was the
      first to postulate that stimulation of angiogenesis alone might be sufficient to
      accelerate ulcer healing in the gastrointestinal tract. Our earlier studies
      demonstrated that therapy with genes or peptides of angiogenic growth factors,
      e.g., bFGF, PDGF and VEGF significantly accelerated healing of experimental
      duodenal ulcers (DU), while blockade of these angiogenic factors resulted in
      impaired healing of DU. However, unlike the angiogenesis in DU, increasing
      evidences from us and others indicate that angiogenesis plays a pathogenic role
      in UC, e.g., VEGF induces an abnormal "pathologic" angiogenesis which interferes
      with UC healing. Recently, another angiogenic factor, placental growth factor
      (PlGF), has also been suggested to be a marker of pathologic angiogenesis and may
      play a critical role in pathogenesis of UC. Although inhibition of pathologic
      angiogenesis by, e.g., anti-VEGF or -PlGF, was demonstrated to be a new approach
      to attenuate UC development, additional data of our and others showed that
      stimulating angiogenesis by administration of PDGF or bFGF significantly
      accelerated healing of UC. Also, activation of Rac1, a small GTPase, markedly
      improved VEGF-induced neovessel architecture defect and reduced vascular
      permeability (VP) in an angiogenic model. Thus, it seems that both angiogenic and
      anti-angiogenic therapies may be used in various stages of UC. More recently, we
      demonstrated that increased VP in colonic mucosa is an early and essential
      element in the initiation and progression of UC. The increased VP is initiated by
      early release of histamine and maintained/aggravated by VEGF, leading to
      perivascular edema, vascular stasis, hypoxia, inflammatory cell infiltration, and
      colonic erosions/ulcers. Inhibition of increased VP prevents or reduces
      development and progression of UC. In this review, we discuss novel pharmacologic
      approaches to prevent UC, differential actions of angiogenic growth factors in UC
      pathogenesis and blocking the early increase in VP in UC development, these new
      findings may provide new insights into the regulation of angiogenesis in UC and
      may lead to development of VP-related drugs to accelerate the healing of UC.

PMID- 22950506
TI  - The impact of asymmetric dimethylarginine (ADAMA), the endogenous nitric oxide
      (NO) synthase inhibitor, to the pathogenesis of gastric mucosal damage.
AB  - This review was designed to provide an update on the role of asymmetric arginine
      (ADMA), the endogenous inhibitor of nitric oxide (NO) synthase in the
      pathophysiology of the upper gastrointestinal (GI) tract. Numerous studies in the
      past confirmed that NO is a multifunctional endogenous gas molecule involved in
      most of the body organs' functional and metabolic processes including the
      regulation of gastrointestinal (GI) secretory functions, motility, maintenance of
      GI integrity, gastroprotection and ulcer healing. NO is metabolized from L
      arginine by enzymatic reaction in the presence of constitutive NO synthase. In
      upper GI tract, NO acts as a potent vasodilator known to increase gastric mucosa
      blood flow, regulates the secretion of mucus and bicarbonate, inhibits the
      gastric secretion and protects the gastric mucosa against the damage induced by a
      variety of damaging agents and corrosive substances. In contrast, ADMA first time
      described by Vallance and coworkers in 1992, is synthesized by the hydrolysis of
      proteins containing methylated arginine amino acids located predominantly within
      the nucleus of cells. This molecule has been shown to competitively inhibit NO
      synthase suggesting its regulatory role in the functions of vascular endothelial
      cells and systemic circulation in humans and experimental animals. Nowadays, ADMA
      is a potentially important risk factor for coronary artery diseases and a marker
      of cardiovascular risk. Increased plasma levels of ADMA have been documented in
      several conditions that are characterized by endothelial dysfunction, including
      hypertension, hypercholesterolemia, hyperglycemia, renal failure and tobacco
      exposure. The role of ADMA in other systems including GI-tract has been so far
      less documented. Nevertheless, ADMA was shown to directly induce oxidative stress
      and cell apoptosis in gastric mucosal cells in vitro and to contribute to the
      inflammatory reaction associated with major human pathogen to gastric mucosa,
      Helicobacter pylori (H.pylori). Infection of gastric mucosa with this germ or H.
      pylori water extract led to marked increase in the plasma concentration of ADMA
      and significantly inhibited bicarbonate secretion, considered as one of the
      important components of upper GI-tract defense system. When administered to
      rodents, ADMA aggravated gastric mucosal lesions injury induced by cold stress,
      ethanol and indomethacin and this worsening effect on gastric lesions was
      accompanied by the significant increase in the plasma level of ADMA. This
      exaggeration of gastric lesions by ADMA was coincided with the inhibition of NO,
      the suppression of gastric blood flow and excessive release of proinflammatory
      cytokine TNF-alpha. This metabolic analog of L-arginine applied to rats was
      exposed to water immersion and restraint stress and ischemia-reperfusion, causing
      an elevation of plasma levels of ADMA and gastric MDA content, which is the
      marker of lipid peroxidation. These effects, including the rise in the plasma
      levels of ADMA in rats with stress and ischemia-reperfusion-induced gastric
      lesions, were attenuated by concomitant treatment with L-arginine, the substrate
      for NO-synthase, and superoxide dismutase (SOD), a reactive oxygen metabolite
      scavenger added to ADMA. We conclude that ADMA could be considered as an
      important factor contributing to the pathogenesis of gastric mucosal damage and
      inflammatory reaction in H. pylori-infected stomach due to inhibition of NO,
      suppression of GI microcirculation, and the proinflammatory and proapoptotic
      actions of this arginine analog.

PMID- 22950507
TI  - Nicotine and gastrointestinal disorders: its role in ulceration and cancer
      development.
AB  - Cigarette smoke has always been the single most preventive cause of death in the
      world. In 2011, over 460,000 died from cigarette smoke-related diseases in US.
      The detrimental effects of cigarette smoke on human beings are due to the
      presence of many carcinogens and other components (e.g. nicotine and tar).
      Nicotine is now accepted as one of the major components responsible for
      gastrointestinal disorders. Cigarette smoking, nicotine and a nicotine-derived
      nitrosamine, 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered
      as risk factors for gastrointestinal cancer, however, the underlying mechanism
      remains largely unknown. Previous studies reported that cigarette smoke and
      nicotine aggravated inflammation not only in the stomach, but also in the colon.
      The carcinogenic actions of cigarette smoke, nicotine and NNK on gastrointestinal
      cancers development have been widely studied. The strong association of
      cyclooxygenase-2 (COX-2) with gastrointestinal diseases has been extensively
      studied, however, due to the unresolved cardiovascular risk, it is of great
      importance to develop other new anti-cancer drugs for the treatment of cancers.
      This current review aims to provide an overview of the effects of cigarette
      smoke, nicotine and NNK on gastrointestinal inflammation, and also the
      carcinogenic properties in cancer development (tumor growth, angiogenesis and
      epithelial-mesenchymal transition). In addition, current studies on nicotinic
      acetylcholine receptors, adrenergic receptors and miRNAs in nicotine-related
      cancer pathogenesis are also highlighted.

PMID- 22950509
TI  - How drugs may work to better protect the gastrointestinal tract: mechanisms
      involved in gastrointestinal tract protection.

PMID- 22950510
TI  - The production and R&D structure of the Brazilian pharmaceutical industry: the
      role of public procurement and public drug production.
AB  - This article examines the use of governmental purchasing power and public
      laboratories to stimulate domestic production and research and development (R&D)
      activities in the Brazilian pharmaceutical industry. Three main areas in which
      public laboratories can play an important role are identified: (1) large-scale
      production of essential medications; (2) production of strategic drugs to reduce
      the trade deficit in the health sector; and (3) in-house research efforts and
      stimulation of R&D in the private sector through public-private partnerships
      (PPPs). The analysis of the production and R&D structure of the Brazilian
      pharmaceutical industry tends to show that the Ministry of Health (MOH)
      purchasing power can be used to nurture the growth of public laboratories and
      generate positive externalities for the private sector. Nonetheless, fieldwork
      data reveal that the lack of alignment between health policies and public
      laboratories' production are resulting in idle production capacity. In order for
      the current governmental strategy to promote industrial growth, there should be a
      division of tasks among public laboratories within a long-term framework, based
      on a stable set of priorities from the MOH.

PMID- 22950508
TI  - Central actions of somatostatin-28 and oligosomatostatin agonists to prevent
      components of the endocrine, autonomic and visceral responses to stress through
      interaction with different somatostatin receptor subtypes.
AB  - Somatostatin was discovered four decades ago and since then its physiological
      role has been extensively investigated, first in relation with its inhibitory
      effect on growth hormone secretion but soon it expanded to extrapituitary actions
      influencing various stressresponsive systems. Somatostatin is expressed in
      distinct brain nuclei and binds to five somatostatin receptor subtypes which are
      also widely expressed in the brain with a distinct distribution pattern. The last
      few years witnessed the discovery of highly selective peptide somatostatin
      receptor agonists and antagonists representing valuable tools to delineate the
      respective pathways of somatostatin signaling. Here we review the centrally
      mediated actions of somatostatin and related selective somatostatin receptor
      subtype agonists to influence the endocrine, autonomic, and visceral components
      of the stress response and basal behavior as well as thermogenesis.

PMID- 22950512
TI  - Plasmodium falciparum, anaemia and cognitive and educational performance among
      school children in an area of moderate malaria transmission: baseline results of
      a cluster randomized trial on the coast of Kenya.
AB  - OBJECTIVES: Studies have typically investigated health and educational
      consequences of malaria among school-aged children in areas of high malaria
      transmission, but few have investigated these issues in moderate transmission
      settings. This study investigates the patterns of and risks for Plasmodium
      falciparum and anaemia and their association with cognitive and education
      outcomes on the Kenyan coast, an area of moderate malaria transmission. METHODS:
      As part of a cluster randomised trial, a baseline cross-sectional survey assessed
      the prevalence of and risk factors for P. falciparum infection and anaemia and
      the associations between health status and measures of cognition and educational
      achievement. Results are presented for 2400 randomly selected children who were
      enrolled in the 51 intervention schools. RESULTS: The overall prevalence of P.
      falciparum infection and anaemia was 13.0% and 45.5%, respectively. There was
      marked heterogeneity in the prevalence of P. falciparum infection by school. In
      multivariable analysis, being male, younger age, not sleeping under a mosquito
      net and household crowding were adjusted risk factors for P. falciparum
      infection, whilst P. falciparum infection, being male and indicators of poor
      nutritional intake were risk factors for anaemia. No association was observed
      between either P. falciparum or anaemia and performance on tests of sustained
      attention, cognition, literacy or numeracy. CONCLUSION: The results indicate that
      in this moderate malaria transmission setting, P. falciparum is strongly
      associated with anaemia, but there is no clear association between health status
      and education. Intervention studies are underway to investigate whether removing
      the burden of chronic asymptomatic P. falciparum and related anaemia can improve
      education outcomes.

PMID- 22950513
TI  - Low-frequency repetitive transcranial magnetic stimulation for the treatment of
      refractory partial epilepsy: a controlled clinical study.
AB  - PURPOSE: This study was designed to evaluate the therapeutic effect of low
      frequency repetitive transcranial magnetic stimulation (rTMS) on patients with
      refractory partial epilepsy. METHODS: Sixty-four patients with refractory focal
      epilepsy were screened and 60 patients were randomly divided into two groups by
      stimulation intensity: 90% (group 1) or 20% (group 2) of resting motor threshold
      (rMT). Seizure frequency and interictal EEG epileptic discharges were compared
      between the baseline and follow-up periods. KEY FINDINGS: Seizures significantly
      decreased following 2-weeks high intensity (90% rMT) rTMS treatment compared with
      baseline level (p < 0.05). rTMS also decreased interictal epilepsy discharges and
      improved the scales of Symptom Checklist-90 significantly (p < 0.05). Seizures
      and spikes in the follow-up period in the patients who received low intensity
      (20% rMT) rTMS did not show any difference compared with baseline data (p > 0.05,
      respectively). SIGNIFICANCE: Low-frequency high intensity rTMS (90% rMT)
      delivered into the epileptogenic zone had a significant antiepileptic effect on
      patients with refractory partial seizures. rTMS treatment can also reduce the
      interictal epileptic discharge frequency and improve the psychological condition
      of these patients.

PMID- 22950514
TI  - Intramolecular Diels-Alder reactions of cycloalkenones: translation of high endo
      selectivity to trans junctions.
AB  - Intramolecular Diels-Alder reactions of cyclobutenone and larger cycloalkenones
      are described. High levels of endo addition attained from Lewis acid catalysis
      translate to trans hydrindene junctions upon fragmentation of the tricyclic
      adducts.

PMID- 22950516
TI  - Interconversion of active and inactive conformations of urokinase-type
      plasminogen activator.
AB  - The catalytic activity of serine proteases depends on a salt-bridge between the
      amino group of residue 16 and the side chain of Asp194. The salt-bridge
      stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some
      serine proteases exist in only partially active forms, in which the amino group
      of residue 16 is exposed to the solvent. Such a partially active state is assumed
      by a truncated form of the murine urokinase-type plasminogen activator (muPA),
      consisting of residues 16-243. Here we investigated the allosteric
      interconversion between partially active states and the fully active state. Both
      a monoclonal antibody (mU3) and a peptidic inhibitor (mupain-1--16) stabilize the
      active state. The epitope of mU3 is located in the 37- and 70-loops at a site
      homologous to exosite I of thrombin. The N-terminus((Ile16)) of muPA((16--243))
      was less exposed upon binding of mU3 or mupain-1--16. In contrast, introduction
      of the mutations F40Y or E137A into muPA((16--243)) increased exposure of the N
      terminus((Ile16)) and resulted in large changes in the thermodynamic parameters
      for mupain-1--16 binding. We conclude that the distorted state of muPA((16--243))
      is conformationally ordered upon binding of ligands to the active site and upon
      binding of mU3 to the 37- and 70-loops. Our study establishes the 37- and 70
      loops as a unique site for binding to compounds stabilizing the active state of
      serine proteases.

PMID- 22950515
TI  - Optimization of flow cytometric detection and cell sorting of transgenic
      Plasmodium parasites using interchangeable optical filters.
AB  - BACKGROUND: Malaria remains a major cause of morbidity and mortality worldwide.
      Flow cytometry-based assays that take advantage of fluorescent protein (FP)
      expressing malaria parasites have proven to be valuable tools for quantification
      and sorting of specific subpopulations of parasite-infected red blood cells.
      However, identification of rare subpopulations of parasites using green
      fluorescent protein (GFP) labelling is complicated by autofluorescence (AF) of
      red blood cells and low signal from transgenic parasites. It has been suggested
      that cell sorting yield could be improved by using filters that precisely match
      the emission spectrum of GFP. METHODS: Detection of transgenic Plasmodium
      falciparum parasites expressing either tdTomato or GFP was performed using a flow
      cytometer with interchangeable optical filters. Parasitaemia was evaluated using
      different optical filters and, after optimization of optics, the GFP-expressing
      parasites were sorted and analysed by microscopy after cytospin preparation and
      by imaging cytometry. RESULTS: A new approach to evaluate filter performance in
      flow cytometry using two-dimensional dot blot was developed. By selecting optical
      filters with narrow bandpass (BP) and maximum position of filter emission close
      to GFP maximum emission in the FL1 channel (510/20, 512/20 and 517/20; dichroics
      502LP and 466LP), AF was markedly decreased and signal-background improve
      dramatically. Sorting of GFP-expressing parasite populations in infected red
      blood cells at 90 or 95% purity with these filters resulted in 50-150% increased
      yield when compared to the standard filter set-up. The purity of the sorted
      population was confirmed using imaging cytometry and microscopy of cytospin
      preparations of sorted red blood cells infected with transgenic malaria
      parasites. DISCUSSION: Filter optimization is particularly important for
      applications where the FP signal and percentage of positive events are relatively
      low, such as analysis of parasite-infected samples with in the intention of gene
      expression profiling and analysis. The approach outlined here results in
      substantially improved yield of GFP-expressing parasites, and requires decreased
      sorting time in comparison to standard methods. It is anticipated that this
      protocol will be useful for a wide range of applications involving rare events.

PMID- 22950517
TI  - Management of hypothyroidism in pregnancy: we must do better.

PMID- 22950518
TI  - Pre-operative echocardiography for hip fractures: time to make it a standard of
      care.

PMID- 22950519
TI  - Towards condom skills: a cross-sectional study of the association between condom
      proficiency, condom problems and STI risk amongst MSM.
AB  - BACKGROUND: Condom use problems are common amongst Scotland's men who have sex
      with men (MSM). To date condom errors have been associated with the likelihood of
      sexually transmitted infections in heterosexual sexually transmitted infection
      (STI) clinic attendees but not in MSM and direct evidence of a link between
      condom problems and STI acquisition in MSM have been lacking. This study
      investigated the possibility of an independent association between condom
      proficiency, condom problems and STI acquisition in MSM in Scotland. METHODS: An
      exploratory observational design employed cross-sectional surveys in both STI
      clinic and community settings. Respondents completed self-report measures of
      socio-demographic variables, scales of condom proficiency and condom problems and
      numbers of different partners with whom men have had unprotected anal intercourse
      (UAI partners) in the preceding year. Self-report data was corroborated with
      clinical STI diagnosis where possible. Analysis included chi-squared and Mann
      Whitney tests and multiple logistic regression. RESULTS: 792 respondents provided
      data with an overall response rate of 70% (n = 459 clinic sample, n = 333
      community sample). Number of UAI partners was the strongest predictor of self
      reported STI acquisition over the previous 12 months (p < 0.001 in both clinic
      and community samples). Demographic characteristics were not associated with self
      reported STI diagnosis. However, condom proficiency score was associated with
      self-reported STI acquisition (p < 0.05 in both samples). Condom problem score
      was also associated with self-reported STI diagnosis in the clinic (p = 0.001)
      but not the community sample. Condom problem score remained associated with self
      reported STI diagnosis in the clinic sample after adjusting for number of UAI
      partners with logistic regression. CONCLUSIONS: This exploratory study highlights
      the potential importance of targeted condom use skills interventions amongst MSM.
      It demands further research examining the utility of condom problem measures in
      wider populations, across prospective and experimental research designs, and a
      programme of research exploring their feasibility as a tool determining candidacy
      for brief interventions.

PMID- 22950521
TI  - Mass-linked immuno-selective assays in targeted proteomics.

PMID- 22950520
TI  - The influence of hepatitis B virus on antiviral treatment with interferon and
      ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection:
      a meta-analysis.
AB  - BACKGROUND: Clinical and laboratory studies have indicated that coinfection with
      hepatitis B virus (HBV) and hepatitis C virus (HCV) can suppress one another,
      eliciting a dominant disease phenotype. To assess whether HBV can influence the
      antiviral effect of treatment on HCV, we performed a meta-analysis to
      comparatively analyze the response to interferon plus ribavirin treatment in
      patients with HBV/HCV coinfection and HCV mono-infection. METHODS: Published
      studies in the English-language medical literature that involved cohorts of
      HBV/HCV coinfection and HCV mono-infection were obtained by searching Medline,
      Cochrane and Embase databases. Studies that compared the efficacy of treatment
      with interferon plus ribavirin in HBV/HCV coinfection and HCV mono-infection were
      assessed. End-of-treatment virological response (ETVR), sustained virological
      response (SVR), HCV relapse rate, and alanine aminotransferase (ALT)
      normalization rate were compared between HBV/HCV coinfection and HCV mono
      infection patients. RESULTS: Five trials involving 705 patients were analyzed. At
      the end of follow-up serum ALT normalization rates in patients with HCV mono
      infection were significantly higher than in patients with HBV/HCV coinfection
      (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.40-0.80, P = 0.001). The
      ETVR and SVR achieved in HBV/HCV coinfection patients were comparable to those in
      HCV mono-infection patients (OR = 1.03, 95% CI: 0.37-2.82, P = 0.96 and OR =
      0.87, 95% CI: 0.62-1.21, P = 0.38, respectively). The rate of relapse for HCV or
      HCV genotype 1 was not significantly different between HBV/HCV coinfection
      patients and HCV mono-infection patients (OR = 1.55, 95% CI: 0.98-2.47, P = 0.06;
      HCV genotype 1: OR = 2.4, 95% CI: 1.17-4.91, P = 0.19). CONCLUSIONS: Treatment
      with interferon and ribavirin achieves similar ETVR and SVR in HBV/HCV
      coinfection and HCV mono-infection. HBV/HCV coinfection patients had
      distinctively lower end of follow-up serum ALT normalization.

PMID- 22950522
TI  - Pharmacokinetics, safety, and tolerability of GLPG0259, a mitogen-activated
      protein kinase-activated protein kinase 5 (MAPKAPK5) inhibitor, given as single
      and multiple doses to healthy male subjects.
AB  - BACKGROUND AND OBJECTIVES: GLPG0259 is a small-molecule inhibitor of mitogen
      activated protein kinase-activated protein kinase 5 (MAPKAPK5), a kinase enzyme
      that plays a role in important inflammatory pathways. The main objectives of the
      phase I clinical studies in early development were to characterize the
      pharmacokinetics, tolerability, and safety of GLPG0259 in healthy subjects,
      including the development of a solid dosage form (free-base pellets and fumarate
      salt capsules) and the potential for interaction of GLPG0259 with methotrexate.
      SUBJECTS AND METHODS: Four phase I studies were initiated. Study 1 was a
      randomized, double-blind, placebo-controlled study to evaluate the safety,
      tolerability, and pharmacokinetics of single ascending doses (1.5-150 mg) and
      multiple oral doses (20 and 50 mg once daily) of GLPG0259 in healthy male
      subjects (n = 34). Study 2 was a randomized, double-blind, placebo-controlled
      study to evaluate the safety, tolerability, and pharmacokinetics of oral multiple
      ascending doses of GLPG0259 (25-75 mg once daily) given for 14 days to healthy
      male subjects, and to get preliminary information on the potential
      pharmacokinetic interaction between GLPG0259 and methotrexate (n = 24). Studies 3
      and 4 were open-label, randomized, crossover studies to compare the oral
      bioavailability of two solid dosage forms of GLPG0259 (a capsule) relative to an
      oral solution after a 100 mg or 50 mg single dose and to evaluate the effect of
      food on these formulations (n = 12 for each study). MAIN OUTCOME MEASURES: The
      non-compartmental pharmacokinetic parameters for plasma concentrations of
      GLPG0259 were determined, and a population pharmacokinetic model of GLPG0259 was
      developed to support the planning of the number and timing of the sparse samples
      to be taken per patient in the phase II study. Safety and tolerability data are
      also summarized. RESULTS: The absorption of GLPG0259 was slow, with a decrease in
      the absorption rate with increasing dose, and there was decreased elimination,
      with an apparent terminal elimination half-life of 26.0 hours. On the basis of
      statistical analysis of variance, the exposure to GLPG0259 increased in
      proportion to the dose over a 30-150 mg single-dose range and a 25-75 mg repeated
      dose range. Between- and within-subject variability in GLPG0259 pharmacokinetics
      was low/moderate (coefficient of variation [CV] 16-30%). After once-daily
      repeated dosing, steady-state plasma concentrations were reached at between 5 and
      8 dosing days, which is consistent with the long apparent elimination half-life
      of GLPG0259. Food increased the bioavailability of GLPG0259 given in a solid
      dosage form. Co-administration of GLPG0259 with a single dose of methotrexate 7.5
      mg did not result in any change in the pharmacokinetic profiles of either
      GLPG0259 or methotrexate. CONCLUSION: In summary, the investigation of
      safety/tolerability and pharmacokinetics in the early development phase showed
      that single and repeated doses of GLPG0259 were safe and well tolerated. The most
      common adverse event reported was mild gastrointestinal discomfort. The
      pharmacokinetics characterized in healthy male subjects showed no major obstacles
      and supports a once-daily oral regimen in patients.

PMID- 22950523
TI  - Effect of ethanol in Paclitaxel injections on the ethanol concentration in
      exhaled breath.
AB  - BACKGROUND: Ethanol is included in certain injectable preparations of anticancer
      drugs to increase their solubility. Since the volume of ethanol in these
      preparations is approximately half of the total injection volume, the potential
      inhibitory effects of ethanol on the central nervous system cannot be
      disregarded, especially considering that patients may drive immediately after
      administration of the medication. Therefore, the concentration of ethanol was
      examined in exhaled breath after administration of paclitaxel, an anticancer
      medication containing ethanol. METHODS: The ethanol concentration in exhaled
      breath immediately after an intravenous infusion of paclitaxel was measured in 30
      patients, using a balloon-type gas detector tube. Correlations between the
      concentration of ethanol in exhaled breath and the total amount of ethanol
      administered or the intravenous infusion speed were calculated. RESULTS: The mean
      ethanol concentration in exhaled breath was 0.028 +/- 0.015 mg/L. The correlation
      between the ethanol concentration in exhaled breath and the total dose of ethanol
      was weak (R2 = 0.25; p = 0.055), while the intravenous infusion speed showed a
      stronger positive correlation with the concentration of ethanol in the breath (R2
      = 0.49; p = 0.11). The maximum concentration of ethanol measured in exhaled
      breath (0.06 mg/L) was equivalent to 40% of the threshold for drunk driving, as
      specified in the Road Traffic Act in Japan. CONCLUSION: In this study, no patient
      had a breath ethanol concentration exceeding the legal threshold for drunk
      driving. However, it is still advisable for patients to avoid driving after
      receiving paclitaxel injections. When driving cannot be avoided, patients should
      wait for a sufficient time after receiving the injection before driving.

PMID- 22950524
TI  - Hippocampal SPARC regulates depression-related behavior.
AB  - SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein
      highly expressed during development, reorganization and tissue repair. In the
      central nervous system, glial cells express SPARC during development and in
      neurogenic regions of the adult brain. Astrocytes control the glutamate receptor
      levels in the developing hippocampus through SPARC secretion. To further
      characterize the role of SPARC in the brain, we analyzed the hippocampal
      dependent adult behavior of SPARC KO mice. We found that SPARC KO mice show
      increased levels of anxiety-related behaviors and reduced levels of depression
      related behaviors. The antidepressant-like phenotype could be rescued by
      adenoviral vector-mediated expression of SPARC in the adult hippocampus, but
      anxiety-related behavior persisted in these mice. To identify the cellular
      mechanisms underlying these behavioral alterations, we analyzed neuronal activity
      and neurogenesis in the dentate gyrus (DG). SPARC KO mice have increased levels
      of neuronal activity, evidenced as more neurons that express c-Fos after a
      footshock. SPARC also affects cell proliferation in the subgranular zone of the
      DG, although it does not affect maturation and survival of new neurons. SPARC
      expression in the adult DG does not revert the proliferation phenotype in KO
      mice, but our results suggest a role of SPARC in limiting the survival of new
      neurons in the DG. This work suggests that SPARC could affect anxiety-related
      behavior by modulating neuronal activity, and that depression-related behavior is
      dependent upon the adult expression of SPARC, which affects adult brain function
      by mechanisms that need to be elucidated. 

PMID- 22950525
TI  - A rapid course through the five electrographic stages of status epilepticus.
AB  - A 54-year-old woman was transferred to a university hospital for severe sepsis
      and multiorgan failure. A complex partial seizure was noted and she was placed on
      continuous electroencephalography (EEG). During EEG monitoring she developed
      generalized convulsive status epilepticus. After consultation with family it was
      decided not to escalate treatment due to her overall medical condition. She
      proceeded sequentially through the five stages of status epilepticus, described
      by Treiman et al. (1990) over 22 h and 30 min and then developed electrocerebral
      silence. This case is significant in that it is the first report of a single
      individual experiencing all five stages of status epilepticus displayed on a
      continuous EEG. The case further demonstrates the rapid progression of status
      epilepticus and exemplifies the need for prompt treatment.

PMID- 22950526
TI  - Exertional leg pain as a manifestation of occult spondyloarthropathy in familial
      Mediterranean fever: an MRI evaluation.
AB  - OBJECTIVES: Familial Mediterranean fever (FMF) is characterized by recurrent
      episodes of fever, peritonitis, arthritis, and pleuritis, caused by neutrophil
      induced sterile serositis. Another clinical manifestation in patients with FMF is
      exertional leg and ankle pain that appears after minor exercise, for which the
      underlying mechanism is obscure. The purpose of the current study was to feature
      distal leg changes in FMF patients complaining of exertional leg pain, using
      magnetic resonance imaging (MRI). METHODS: Eleven patients with FMF who suffer
      from exertional leg pain (eight males, three females; mean age 33 years) and six
      unaffected controls (three males, three females; mean age 39 years) underwent MRI
      (3 T) of the ankle, including conventional T1 and T2 with fat saturation
      sequences, before and after graded exercise on a treadmill. Clinical and genetic
      data and sacroiliac radiographs were obtained. RESULTS: Ten patients (91%) with
      FMF but none of the control group had signs compatible with enthesitis of the
      Achilles tendon, long plantar ligament, or the plantar fascia (including
      enthesophytes, erosions, and bone marrow oedema). Nine patients (80%) had
      radiographic signs of sacroiliitis on the pelvic radiograph. CONCLUSIONS:
      Exertional leg pain in FMF patients, shown to be associated with signs of
      enthesopathy on imaging, may be included within the spectrum of
      spondyloarthropathy.

PMID- 22950527
TI  - Surgeon General's Call to Action to Support Breastfeeding: significant actions in
      the first year.

PMID- 22950528
TI  - Chromium(IV)-peroxo complex formation and its nitric oxide dioxygenase
      reactivity.
AB  - The O(2) and NO reactivity of a Cr(II) complex bearing a 12-membered
      tetraazamacrocyclic N-tetramethylated cyclam (TMC) ligand, [Cr(II)(12
      TMC)(Cl)](+) (1), and the NO reactivity of its peroxo derivative, [Cr(IV)(12
      TMC)(O(2))(Cl)](+) (2), are described. By contrast to the previously reported
      Cr(III)-superoxo complex, [Cr(III)(14-TMC)(O(2))(Cl)](+), the Cr(IV)-peroxo
      complex 2 is formed in the reaction of 1 and O(2). Full spectroscopic and X-ray
      analysis revealed that 2 possesses side-on eta(2)-peroxo ligation. The
      quantitative reaction of 2 with NO affords a reduction in Cr oxidation state,
      producing a Cr(III)-nitrato complex, [Cr(III)(12-TMC)(NO(3))(Cl)](+) (3). The
      latter is suggested to form via a Cr(III)-peroxynitrite intermediate. [Cr(II)(12
      TMC)(NO)(Cl)](+) (4), a Cr(II)-nitrosyl complex derived from 1 and NO, could also
      be synthesized; however, it does not react with O(2).

PMID- 22950529
TI  - Vital capacity and inspiratory capacity as additional parameters to evaluate
      bronchodilator response in asthmatic patients: a cross sectional study.
AB  - BACKGROUND: Bronchodilator response in patients with asthma is evaluated based on
      post-bronchodilator increase in forced expiratory volume in one second (FEV1) and
      forced vital capacity (FVC). However, the need for additional parameters, mainly
      among patients with severe asthma, has already been demonstrated. METHODS: The
      aim of this study was to evaluate the usefulness of vital capacity (VC) and
      inspiratory capacity (IC) to evaluate bronchodilator response in asthma patients
      with persistent airflow obstruction. The 43 asthma patients enrolled in the study
      were stratified into moderate or severe airflow obstruction groups based on
      baseline FEV1. All patients performed a 6-minute walk test before and after the
      bronchodilator (BD). A bipolar visual analogue scale post-BD was performed to
      assess clinical effect. The correlation between VC and IC and clinical response,
      determined by visual analogue scale (VAS) and 6-minute walk test (6MWT), was
      investigated. RESULTS: Patients in the severe group presented: 1) greater
      bronchodilator response in VC (48% vs 15%, p = 0.02), 2) a significant
      correlation between VC variation and the reduction in air trapping (Rs = 0.70; p
      < 0.01), 3) a significant agreement between VC and VAS score (kappa = 0.57; p <
      0.01). There was no correlation between IC and the reduction in air trapping or
      clinical data. CONCLUSIONS: VC may be a useful additional parameter to evaluate
      bronchodilator response in asthma patients with severe airflow obstruction.

PMID- 22950530
TI  - A cooperative role for the counteranion in the PCl5-initiated living, cationic
      chain growth polycondensation of the phosphoranimine Cl3P?NSiMe3.
AB  - The counteranion associated with the cationic initiator [Cl(3)P?N?PCl(3)](+)
      ([4](+)) generated during the PCl(5)-initiated living, cationic chain growth
      polycondensation of the N-silylphosphoranimine Cl(3)P?NSiMe(3) (3) to give
      poly(dichlorophosphazene), [N?PCl(2)](n) (2), has been found to have a dramatic
      effect on the polymerization. When the counteranion of [4](+) was changed from
      PCl(6)(-) or Cl(-) to the weakly coordinating anions [BAr*(F)(4)](-) and
      [BAr(F)(4)](-) (Ar*(F) = 3,5-{CF(3)}(2)C(6)H(3), Ar(F) = C(6)F(5)) instead of the
      polymerization of 3 being complete in 4-6 h, no reaction was observed after 24 h.
      Remarkably, the polymerization of 3 may be initiated by Cl(-) anions even in the
      absence of an active cation such as [4](+). However, in the presence of [4](+),
      the reaction proceeded significantly faster and allowed for molecular weight
      control. These results reveal that the currently accepted mechanism for the
      PCl(5)-initiated living polymerization of 3 needs to be revised to reflect the
      key role of the counteranion present.

PMID- 22950531
TI  - Maternal behavior in transgenic mice with reduced fibroblast growth factor
      receptor function in gonadotropin-releasing hormone neurons.
AB  - BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are
      necessary for the proper development of gonadotropin-releasing hormone (GnRH)
      neurons, which are key activators of the hypothalamo-pituitary-gonadal axis.
      Transgenic mice that have the targeted expression of a dominant negative FGFR
      (dnFGFR) in GnRH neurons (dnFGFR mice) have a 30% decrease of GnRH neurons.
      Additionally, only 30-40% of the pups born to the transgenic dams survive to
      weaning age. These data raised the possibility that FGFR defects in GnRH neurons
      could adversely affect maternal behavior via novel mechanisms. METHODS: We first
      determined if defective maternal behavior in dnFGFR mothers may contribute to
      poor pup survival by measuring pup retrieval and a battery of maternal behaviors
      in primiparous control (n=10-12) and dnFGFR (n=13-14) mothers. Other endocrine
      correlates of maternal behaviors, including plasma estradiol levels and
      hypothalamic pro-oxyphysin and GnRH transcript levels were also determined using
      enzyme-linked immunoassay and quantitative reverse transcription polymerase chain
      reaction, respectively. RESULTS: Maternal behaviors (% time crouching with pups,
      time off pups but not feeding, time feeding, and total number of nesting bouts)
      were not significantly different in dnFGFR mice. However, dnFGFR dams were more
      likely to leave their pups scattered and took significantly longer to retrieve
      each pup compared to control dams. Further, dnFGFR mothers had significantly
      lower GnRH transcripts and circulating E2, but normal pro-oxyphysin transcript
      levels. CONCLUSIONS: Overall, this study suggests a complex scenario in which a
      GnRH system compromised by reduced FGF signaling leads to not only suboptimal
      reproductive physiology, but also suboptimal maternal behavior.

PMID- 22950532
TI  - A procedure for Alcian blue staining of mucins on polyvinylidene difluoride
      membranes.
AB  - The isolation and characterization of mucins are critically important for
      obtaining insight into the molecular pathology of various diseases, including
      cancers and cystic fibrosis. Recently, we developed a novel membrane
      electrophoretic method, supported molecular matrix electrophoresis (SMME), which
      separates mucins on a polyvinylidene difluoride (PVDF) membrane impregnated with
      a hydrophilic polymer. Alcian blue staining is widely used to visualize
      mucopolysaccharides and acidic mucins on both blotted membranes and SMME
      membranes; however, this method cannot be used to stain mucins with a low acidic
      glycan content. Meanwhile, periodic acid-Schiff staining can selectively
      visualize glycoproteins, including mucins, but is incompatible with glycan
      analysis, which is indispensable for mucin characterizations. Here we describe a
      novel staining method, designated succinylation-Alcian blue staining, for
      visualizing mucins on a PVDF membrane. This method can visualize mucins
      regardless of the acidic residue content and shows a sensitivity 2-fold higher
      than that of Pro-Q Emerald 488, a fluorescent periodate Schiff-base stain.
      Furthermore, we demonstrate the compatibility of this novel staining procedure
      with glycan analysis using porcine gastric mucin as a model mucin.

PMID- 22950533
TI  - Opioid-induced bowel dysfunction: pathophysiology and management.
AB  - Opioids are the most commonly prescribed medications to treat severe pain in the
      Western world. It has been estimated that up to 90% of American patients
      presenting to specialized pain centres are treated with opioids. Along with their
      analgesic properties, opioids have the potential to produce substantial side
      effects, such as nausea, cognitive impairment, addiction and urinary retention.
      In the gut, opioids exert their action on the enteric nervous system, where they
      bind to the myenteric and submucosal plexuses, causing dysmotility, decreased
      fluid secretion and sphincter dysfunction, which all leads to opioid-induced
      bowel dysfunction (OIBD). In the clinic, this is reported as nausea, vomiting,
      gastro-oesophageal reflux-related symptoms, constipation, etc. One of the most
      severe symptoms is constipation, which can be assessed using different scales for
      subjective assessment. Objective methods such as radiography and colonic transit
      time can also be used, together with manometry and evaluation of anorectal
      function to explore the pathophysiology. Dose-limiting adverse symptoms of OIBD
      can lead to insufficient pain treatment. Even though several treatment strategies
      are available, the side effects are still a major challenge. Traditional
      laxatives are normally prescribed but they are often insufficient to alleviate
      symptoms, especially those from the upper gastrointestinal tract. Newer
      prokinetics, such as prucalopride and lubiprostone, may be more effective in
      alleviating OIBD. Another treatment approach is co-administration of opioid
      antagonists, which either cannot cross the blood-brain barrier or selectively
      target opioid receptors in the gastrointestinal tract. However, although these
      new agents have proved to be more efficacious than placebo, clinical trials still
      need to prove their superiority to standard co-prescribed laxative regimes.

PMID- 22950535
TI  - Nomegestrol acetate/estradiol: in oral contraception.
AB  - Nomegestrol acetate/estradiol is a combined oral contraceptive with approval in
      many countries. This fixed-dose combination tablet contains nomegestrol acetate,
      a highly selective progestogen, and estradiol, a natural estrogen. It is the
      first monophasic combined oral contraceptive to contain estradiol, and is taken
      in 28-day cycles, consisting of 24 active therapy days with 4 placebo days (i.e.
      24/4-day cycles). In two large, 1-year, randomized, open-label, multicentre,
      phase III trials in healthy adult women (aged 18-50 years), nomegestrol
      acetate/estradiol was at least as effective as drospirenone/ethinylestradiol as
      contraceptive therapy, as the pregnancy rates in women aged 18-35 years (primary
      efficacy population) in terms of the Pearl Index (primary endpoint) were
      numerically lower with nomegestrol acetate/estradiol, although the between-group
      difference was not statistically significant. In both trials, nomegestrol
      acetate/estradiol was given in a 24/4-day cycle, and
      drospirenone/ethinylestradiol was given in a 21/7-day cycle. The criteria for
      using condoms in case of forgotten doses were less stringent in the nomegestrol
      acetate/estradiol group than in the drospirenone/ethinylestradiol group.
      Nomegestrol acetate/estradiol therapy for up to 1 year was generally well
      tolerated in healthy adult women, with an acceptable tolerability profile in line
      with that expected for a combined oral contraceptive. The most commonly reported
      adverse events were acne and abnormal withdrawal bleeding (most often shorter,
      lighter or absent periods). Overall, compared with drospirenone/ethinylestradiol,
      nomegestrol acetate/estradiol appeared to be associated with less favourable acne
      related outcomes, and shorter, lighter or absent periods.

PMID- 22950536
TI  - Bendamustine: a review of its use in the management of chronic lymphocytic
      leukaemia, rituximab-refractory indolent non-Hodgkin's lymphoma and multiple
      myeloma.
AB  - Bendamustine (Levact(r)) is an alkylating agent consisting of three structural
      elements: a 2-chloroethylamine alkylating group; a butyric acid side chain; and a
      benzimidazole ring. Although its precise mechanism of action is as yet unknown,
      it appears to exert its antineoplastic effects via a different mechanism to those
      of other alkylating agents. This article reviews the utilization of intravenous
      bendamustine in patients with chronic lymphocytic leukaemia (CLL), rituximab
      refractory indolent non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM),
      focusing on indications for which the agent is approved in the EU. As
      monotherapy, bendamustine was effective in the first-line treatment of adults
      with CLL, significantly prolonging progression-free survival (PFS) and improving
      the overall response (OR) rate after a median duration of follow-up of 35 months
      compared with chlorambucil in a randomized, open-label, multinational, phase III
      study. PFS and the OR rate were at least 2-fold greater with bendamustine than
      with chlorambucil when data from the overall patient population were stratified
      by Binet stage. In the treatment of adults with rituximab-refractory indolent
      NHL, monotherapy with bendamustine was efficacious, with an OR achieved by at
      least three-quarters of patients in two noncomparative multicentre studies.
      Patients with follicular histology or those who had responded or were refractory
      to their previous chemotherapy regimen (including alkylator therapy) also
      appeared to respond to bendamustine monotherapy. Front-line combination therapy
      with bendamustine plus prednisone was significantly more effective than
      combination therapy with melphalan plus prednisone in prolonging the time to
      treatment failure, according to a randomized, open-label multicentre, phase III
      study in adults with MM. Moreover, the benefits of bendamustine plus prednisone
      appeared to be maintained beyond 30 months, with a retrospective calculation of
      PFS demonstrating a borderline statistical significance in favour of bendamustine
      plus prednisone over melphalan plus prednisone. The tolerability profile of
      bendamustine in adults with CLL, indolent NHL or MM was mostly consistent with
      the known toxicities of the agent, with adverse events often managed with dose
      modifications. Although further data are required to fully establish the
      comparative efficacy of intravenous bendamustine in the management of CLL,
      rituximab-refractory indolent NHL or MM, it appears to be a useful addition to
      the armamentarium of currently available therapies for these haematological
      malignancies.

PMID- 22950538
TI  - Fatty acid composition including trans-fatty acids in edible oils and fats:
      probable intake in Indian population.
AB  - The susceptibility of trans-fat to the human health risk prompted the Food and
      Agriculture Organization (FAO) and World Health Organization (WHO) to prepare
      regulations or compulsory claims for trans-fatty acids (TFA) in edible oils and
      fats. In this study, analysis of fatty acid composition and TFA content in edible
      oils and fats along with the possible intake of trans-fat in Indian population
      was carried out. The analysis was carried out as per the Assn. of Official
      Analytical Chemists (AOAC) methodology and the results were statistically
      analyzed. The average TFA content in nonrefined mustard and refined soybean oils
      exceeded by 1.16- to 1.64-fold as compared to the Denmark limit of 2% TFA in fats
      and oils destined for human consumption. In branded/nonbranded butter and butter
      oil samples, average TFA limit exceeded by 4.2- to 9.5-fold whereas hydrogenated
      vegetable oil (HVO) samples exceeded the limit by 9.8-fold, when compared to
      Denmark standards. The probable TFA intake per day through different oils in
      Indian population were found to be less than WHO recommendation. However Punjab
      having highest consumption of HVO (-15 g/d) showed 1.09-fold higher TFA intake
      than the WHO recommendation, which is alarming and may be one of the factors for
      high cardiovascular disease mortality rate that needs further elucidation. Thus
      there is a need to prescribe TFA limit for edible oil, butter, and butter oil in
      India and to reduce the already proposed TFA levels in HVO to safeguard the
      health of consumers. PRACTICAL APPLICATION: The probable daily intake of trans
      fatty acid (TFA) especially through hydrogenated vegetable oil (HVO) was
      assessed. In absence of any specification for TFA and fatty acid composition for
      edible oils, butter, and butter samples, a pressing need was felt to prescribe
      TFA limit in India. The study indicates that TFA intake through HVO consumption
      is higher in States like Punjab than the recommended daily intake prescribed by
      WHO. Hence, strategies should be adopted to either decrease the consumption of
      HVO or to modify the industrial processing method of HVO with less content of TFA
      to safeguard the health of consumers.

PMID- 22950539
TI  - Impact of substrate overloading on archaeal populations in anaerobic digestion of
      animal waste.
AB  - AIMS: To characterize adaptive changes in methanogenic microbial community in
      response to substrate overloading and identify potential linkages between process
      performance and microbial community composition. METHODS AND RESULTS: Triplicate
      continuous anaerobic digesters were developed as model anaerobic digestion
      processes, which were subsequently disrupted by substrate overloading. The clone
      library analysis of archaeal communities experiencing substrate overloading
      showed that populations related to Methanosaeta were the dominant methanogens
      before and after substrate overloading, suggesting the functional importance of
      these acetoclastic methanogens in balanced anaerobic digestion processes
      characterized with low organic acids concentrations. Population redundancy in
      Methanosaeta increased following substrate overloading with the emergence of
      additional populations of Methanosaeta. More importantly, the methanogenic
      community responded to process imbalance with greater functional diversity with
      increased abundance of functionally distinct hydrogenotrophic and acetoclastic
      methanogens, which likely enhanced the functional stability of anaerobic
      digestion during disruptions in the anaerobic food web under process
      perturbation. Crenarchaeota were identified as persistent constituents of the
      archaeal communities in anaerobic digestion, warranting further efforts to
      identifying the functions of these phylogenetically distinct populations in
      anaerobic digestion. CONCLUSIONS: Substrate overloading in anaerobic digestion
      resulted in an increased functional diversity of the methanogenic community,
      which enhanced the capacity to overcome subsequent occurrences of process
      perturbations without performance disruption, providing a potential strategy to
      maintain process stability in anaerobic digestion. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Anaerobic digestion is a sustainable option for waste treatment and
      renewable energy production. However, process instability resulting from
      variations in substrate loading has been one of the obstacles to the broader
      adoption of anaerobic digestion technology. Insight into the linkages between
      process performance and microbial community gained in this study is valuable for
      developing strategies for the mitigation of the impact of substrate overloading
      on anaerobic digestion processes.

PMID- 22950540
TI  - Reliability and relative validity of a food frequency questionnaire to assess
      food group intakes in New Zealand adolescents.
AB  - BACKGROUND: Due to the absence of a current and validated food frequency
      questionnaire (FFQ) for use in New Zealand adolescents, there is a need to
      develop one as a cost-effective way to assess adolescents' food patterns. This
      study aims to examine the test-retest reliability and relative validity of the
      New Zealand Adolescent FFQ (NZAFFQ) to assess food group intake in adolescents
      aged 14 to 18 years. METHODS: A non-quantitative (without portion size), 72-item
      FFQ was developed and pretested. Fifty-two participants (aged 14.9 +/- 0.8 years)
      completed the NZAFFQ twice within a two-week period for test-retest reliability.
      Forty-one participants (aged 15.1 +/- 0.9 years) completed a four-day estimated
      food record (4DFR) in addition to the FFQs to enable assessment of validity.
      Spearman's correlations and cross-classification analyses were used to examine
      relative validity while intra-class correlations were additionally used for test
      retest reliability. RESULTS: Weekly intakes were estimated for each food item and
      aggregated into 34 food groups. The median Spearman's correlation coefficient
      (SCC) between FFQ administrations was 0.71. SCCs ranged from 0.46 for fruit juice
      or cordial to 0.87 for non-standard milk. The median intra-class correlation
      coefficient (ICC) between FFQ administrations was 0.69. The median SCC between
      food groups from the FFQ and the 4DFR was 0.40 with the highest SCC seen for
      standard milk (0.70). The exact agreement between the methods in ranking
      participants into thirds was highest for meat alternatives (78%), but lowest for
      red or yellow vegetables and potatoes (27%). The mean percent of participants
      misclassified into extreme thirds for food group intake was 12%. CONCLUSIONS:
      Despite a small sample size, the NZAFFQ exhibited good to excellent short-term
      test-retest reliability and reasonable validity in ranking the majority of the
      food group intakes among adolescents aged 14 to 18 years. The comparability of
      the validity to that in the current literature suggests that the NZAFFQ may be
      used among adolescent New Zealanders to identify dietary patterns and rank them
      according to food group intake.

PMID- 22950541
TI  - Influence of fluid intake on soccer performance in a temperate environment.
AB  - The study aim was to examine the effect of fluid intake and dehydration on soccer
      skill and high-intensity, intermittent-running performance after 90-minutes
      intermittent exercise (Loughborough Intermittent Shuttle Test). Thirteen semi
      professional, men soccer-players completed, the 90-minute intermittent exercise
      on three fluid trials: prescribed fluid equal to sweat loss (1.65 +/- 0.17
      litres: Mean +/- s), ad libitum fluid (0.85 +/- 0.19 litres) and no fluid. After
      the intermittent exercise, dehydration was equivalent to 0.3 +/- 0.1, 1.1 +/-
      0.2, 2.5 +/- 0.4% body mass loss on the prescribed-fluid, ad libitum-fluid and no
      fluid trials, respectively. Soccer-skill and high-intensity, intermittent-running
      performance, as assessed by the Loughborough Soccer Passing and Shooting Tests,
      and the Yo-Yo Intermittent Recovery Test, declined after the intermittent
      exercise compared with assessments made before. The decline in performance was
      however similar on all fluid trials (P > 0.34 for interactions and effect sizes
      were trivial or small). These effect sizes suggest larger fluid intakes had
      limited and inconsistent (both beneficial and detrimental) effects on
      performance. In conclusion the results suggest that fluid intake during 90
      minutes of intermittent exercise and modest dehydration have limited and
      inconsistent effects on soccer passing and shooting skill or high-intensity,
      intermittent-running in a temperate environment.

PMID- 22950534
TI  - Sedation for critically ill or injured adults in the intensive care unit: a
      shifting paradigm.
AB  - As most critically ill or injured patients will require some degree of sedation,
      the goal of this paper was to comprehensively review the literature associated
      with use of sedative agents in the intensive care unit (ICU). The first and
      selected latter portions of this article present a narrative overview of the
      shifting paradigm in ICU sedation practices, indications for uninterrupted or
      prolonged ICU sedation, and the pharmacology of sedative agents. In the second
      portion, we conducted a structured, although not entirely systematic, review of
      the available evidence associated with use of alternative sedative agents in
      critically ill or injured adults. Data sources for this review were derived by
      searching OVID MEDLINE and PubMed from their first available date until May 2012
      for relevant randomized controlled trials (RCTs), systematic reviews and/or meta
      analyses and economic evaluations. Advances in the technology of mechanical
      ventilation have permitted clinicians to limit the use of sedation among the
      critically ill through daily sedative interruptions or other means. These
      practices have been reported to result in improved mortality, a decreased length
      of ICU and hospital stay and a lower risk of drug-associated delirium. However,
      in some cases, prolonged or uninterrupted sedation may still be indicated, such
      as when patients develop intracranial hypertension following traumatic brain
      injury. The pharmacokinetics of sedative agents have clinical importance and may
      be altered by critical illness or injury, co-morbid conditions and/or drug-drug
      interactions. Although use of validated sedation scales to monitor depth of
      sedation is likely to reduce adverse events, they have no utility for patients
      receiving neuromuscular receptor blocking agents. Depth of sedation monitoring
      devices such as the Bispectral Index (BIS(c)) also have limitations. Among
      existing RCTs, no sedative agent has been reported to improve the risk of
      mortality among the critically ill or injured. Moreover, although propofol may be
      associated with a shorter time to tracheal extubation and recovery from sedation
      than midazolam, the risk of hypertriglyceridaemia and hypotension is higher with
      propofol. Despite dexmedetomidine being linked with a lower risk of drug
      associated delirium than alternative sedative agents, this drug increases risk of
      bradycardia and hypotension. Among adults with severe traumatic brain injury,
      there are insufficient data to suggest that any single sedative agent decreases
      the risk of subsequent poor neurological outcomes or mortality. The lack of
      examination of confounders, including the type of healthcare system in which the
      investigation was conducted, is a major limitation of existing pharmacoeconomic
      analyses, which likely limits generalizability of their results.

PMID- 22950542
TI  - Emergency neurosurgical referrals in the North East of England - trends over four
      years 2008-2011.
AB  - AIMS: On-call referrals are a considerable part of the neurosurgical workload.
      Many neurosurgical centres in the UK have now adopted the practice of maintenance
      of electronic databases to keep records of on-call activity. We analysed the
      neurosurgical on-call referrals database maintained at the Newcastle General
      Hospital (NGH)/Royal Victoria Infirmary (RVI) to assess any trends in the nature
      of referrals. METHODS: Retrospective review and statistical analysis of a
      contemporaneously populated referrals database, maintained at the Regional
      Neurosciences Unit in Newcastle. Data were analysed from August 2008 to April
      2011. A three point moving average was used to depict trend in the number of
      referrals. Descriptive statistics were used to display other trends. Analysis was
      conducted using JMP 8.0.2 (SAS Institute, Cary, NC, USA). RESULTS: Our analysis
      reveals that the number of emergency referrals to neurosurgery in the North East
      of England is increasing year-on-year. Mean number of referrals per day has
      increased by almost 5 over the study period (9.06 in 2008 compared to 13.93 in
      2011). The major diagnoses that account for this increase are lumbar degenerative
      conditions, intracerebral haematomas, spinal trauma and subarachnoid haemorrhage.
      50% of the patients are referred out of hours and approximately one-third are
      admitted. In contrast, 47% of all referrals to rule out a cauda equina syndrome,
      need admission for scanning. General practitioners (GP) are the single biggest
      source of referral outside of the parent NHS trust and 47% of the GP referrals
      are regarding lumbar degenerative conditions and cauda equina syndrome.
      CONCLUSIONS: Continuously increasing referrals have implications on cost,
      staffing and sustainability of the service. Alternative referral pathways,
      especially for referrals from primary care, must be considered to restore the on
      call workload to 'true' neurosurgical emergencies.

PMID- 22950544
TI  - Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the
      severity of cystic fibrosis.
AB  - BACKGROUND: The most common cystic fibrosis (CF) manifestation is the progressive
      chronic obstructive pulmonary disease caused by deficiency, dysfunction, or
      absence of the CFTR (Cystic Fibrosis Transmembrane Regulator) protein on the
      apical surface of the cells in the respiratory tract. The use of bronchodilators
      (BD), and inhaled corticosteroids (IC) have been suggested for the management of
      airway inflammation in CF. The effectiveness of BD and IC have been verified,
      proven in laboratory and in the clinical treatment for asthma patients. However,
      in CF, the effectiveness of these drugs is controversial. The extent of asthma's
      response to BD depends on the presence of polymorphisms in the ADRB2 gene. In
      contrast, in CF, little is known about the response to the BD and the association
      of CF's severity with the different polymorphisms in ADRB2 gene. In this context,
      our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in
      ADRB2 gene are associated with severity and with the bronchodilator response in
      CF patients. METHOD: Cross-sectional study of 122 CF patients subjected to
      analysis of mutations in the CFTR gene, polymorphisms in ADRB2 gene, along with
      clinical and laboratorial characteristics of severity. RESULT: The Arg16Gly
      polymorphism in ADRB2 gene was associated with pancreatic insufficiency(p:0.009),
      Bhalla score(p:0.039), forced expiratory volume in the first
      second[FEV1(%)](p:0.003), forced expiratory flow between 25 and 75% of the forced
      vital capacity-FVC[FEF25-75(%)](p:0.008) and lower age at the first isolation of
      the Pseudomonas aeruginosa(p:0.012). The response to the BD spirometry was
      associated with clinical severity markers, FEV1(%)(p:0.011) and FEF25
      75(%)(p:0.019), for the Arg16Gly polymorphism in the ADRB2 gene. The haplotype
      analysis showed association with the FEV1/FVC marker from the spirometry test,
      before and after using the BD, with higher values in the group with Gly/Gly and
      Glu/Glu, respectively, for the Arg16Gly and Gln27Glu polymorphisms. The analysis
      by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly
      was respondent by 17.35% and Gln27Glu by 6.8% in variation found. CONCLUSION:
      There was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2
      gene with CF's severity and bronchodilator response.

PMID- 22950545
TI  - Powerful amino diol catalyst for effecting the direct asymmetric conjugate
      addition of aldehydes to acrylates.
AB  - Di-tert-butyl methylenemalonate (1) could be employed as a reactive equivalent of
      a three-carbon Michael acceptor such as acrylate in a direct asymmetric conjugate
      addition of aldehydes catalyzed by an axially chiral amino diol (S)-3a.
      Furthermore, acrylate, an unexplored and challenging substrate in enamine
      catalysis, has also been successfully employed in asymmetric conjugate addition
      reaction. Relatively inert acrylate is doubly activated by polyfluoroalkyl group
      of 2 and the hydroxyl group on the axially chiral amino diol catalyst (S)-3b,
      giving corresponding conjugate adducts in high yield with excellent enantiomeric
      excess. The obtained conjugate addition products were readily converted to
      synthetically useful and important chiral building blocks.

PMID- 22950546
TI  - Treatment of adolescents with depression: the effect of transference
      interventions in a randomized controlled study of dynamic psychotherapy.
AB  - BACKGROUND: Depression in adolescents seems to be a growing problem that causes
      mental suffering and prevents young people from joining the workforce. There is
      also a high risk of relapse during adult life. There is emerging evidence for the
      effect of psychodynamic psychotherapy in adolescents. In-session relational
      intervention (that is, transference intervention) is a key component of
      psychodynamic psychotherapy. However, whether depressed adolescents profit most
      from psychodynamic psychotherapy with or without transference interventions has
      not been stated. OBJECT: The effect of transference interventions in depressed
      adolescents and the moderator moderating effect of quality of object relations,
      personality disorder and gender will be explored. METHODS AND STUDY DESIGN: The
      First Experimental Study of Transference Work-In Teenagers (FEST-IT) will be a
      randomized clinical trial with a dismantling design. The study is aimed to
      explore the effects of transference work in psychodynamic psychotherapy for
      adolescents with depression. One hundred patients ages 16 to 18 years old will be
      randomized to one of two treatment groups, in both of which general psychodynamic
      techniques will be used. The patients will be treated over 28 weeks with either a
      moderate level of transference intervention or no transference intervention.
      Follow-up will be at 1 year after treatment termination. The outcome measures
      will be the Psychodynamic Functioning Scales (PFS), Inventory of Interpersonal
      Problems-Circumplex Version (IIP-C), Global Assessment of Functioning (GAF), and
      the total mean score of Symptom Checklist-90 (Global Severity Index; GSI), Beck
      Depression Inventory (BDI), and Montgomery Asberg Rating Scale (MADRS). The
      quality of adolescents' relationships will be a central focus of the study, and
      the Adolescent Relationship Scales (ARS) and Differentiation-Relatedness Scale
      (DRS) will also be used. Change will be assessed using linear-mixed models.
      Gender personality disorder (PD) and quality of object relations (QOR) will be
      the preselected putative moderators. DISCUSSION: The object of this clinical
      trial is to explore the effect of transference interventions in psychodynamic
      psychotherapy in adolescents with a major depressive disorder. Using a randomized
      and dismantling design, we hope that the study will add more specific knowledge
      to the evidence base. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01531101First Experimental Study of Transference work Work-In Teenagers (FEST
      IT).

PMID- 22950547
TI  - Omalizumab for the treatment of severe persistent allergic asthma in children
      aged 6-11 years: a NICE single technology appraisal.
AB  - Following a licence extension to include those aged 6-11 years, the National
      Institute for Health and Clinical Excellence (NICE) invited the manufacturer of
      omalizumab (Novartis Pharmaceuticals UK) to submit evidence for the clinical and
      cost effectiveness of this drug for patients with severe persistent allergic
      asthma in this age bracket. NICE had previously considered the use of omalizumab
      in patients aged 12 years and over. The Centre for Reviews and Dissemination
      (CRD) and the Centre for Health Economics (CHE) at the University of York were
      commissioned as the Evidence Review Group (ERG) to critically appraise the
      evidence presented by the manufacturer. This article summarizes that review of
      the evidence, the deliberations of the NICE Appraisal Committee and the resulting
      NICE guidance. The ERG critically reviewed the evidence presented in the
      manufacturer's submission and identified areas requiring clarification, for which
      the manufacturer provided additional evidence. The relevant patient population
      was patients aged 6-11 years of age with severe persistent allergic
      immunoglobulin E-mediated asthma whose condition remained uncontrolled despite
      best standard care with high-dose inhaled corticosteroids and a long-acting
      inhaled beta2-agonist. The main clinical effectiveness data were derived from a
      pre-planned subgroup analysis of a single randomized controlled trial comparing
      omalizumab plus standard therapy against standard therapy alone. At a 52-week
      follow-up, the only outcome to show a statistically significant benefit of
      omalizumab compared with placebo was the number of exacerbations defined as
      'clinically significant' [CS] (relative risk [RR] 0.504; 95% CI 0.350, 0.725; p <
      0.001). At the ERG's request, the manufacturer provided analyses stratified by
      baseline exacerbation rate, which indicated the effect of omalizumab on CS
      exacerbations was statistically significant only for those children with >=3
      exacerbations as baseline. The ERG identified a number of issues relating to the
      clinical effectiveness results: it was unclear whether the pre-planned subgroup
      analysis had sufficient power; the definition of CS exacerbation was less severe
      than that used in UK clinical practice; and the method for imputing exacerbations
      for those who withdrew from treatment may have underestimated the exacerbation
      rate. The incremental cost-effectiveness ratio based on the manufacturer's
      results was considerably above the threshold range stated in the NICE Guide to
      the Methods of Technology Appraisal. The ERG identified numerous issues relating
      to the cost-effectiveness results, which included the following: the 10-year time
      horizon for treatment may exceed that in clinical practice; the assumption of
      constant exacerbation rates over a lifetime given that adolescence is expected to
      impact on the severity of asthma; and whether it is appropriate to use health
      related quality-of-life data collected in adults for children. The ERG concluded
      that omalizumab appears to reduce CS exacerbations but there was no evidence of
      improvement in daily symptoms, CS severe (CSS) exacerbations or hospitalization
      rates. The main driver of cost effectiveness was the reduction in asthma-related
      mortality associated with a reduction in CSS exacerbations. As the number of CSS
      exacerbations avoided was low, as is asthma-related mortality in children, the
      potential small gain in QALYs associated with omalizumab was not sufficient to
      compensate for the high treatment cost even under the most favourable scenario
      analyses. The Appraisal Committee recommended that omalizumab should not be
      routinely provided for the treatment of severe persistent allergic asthma in
      children aged 6-11 years.

PMID- 22950548
TI  - Myocardial calcium overload during graded hypothermia and after rewarming in an
      in vivo rat model.
AB  - AIM: Mechanisms underlying cardiac contractile dysfunction during and after
      rewarming from hypothermia remain largely unknown. We have previously reported
      myocardial post-hypothermic calcium overload to be the culprit. The aim of the
      present study was to measure changes in myocardial [Ca(2+) ](i) during graded
      hypothermia and after rewarming in an anesthetized, intact rat model, using the
      (45) Ca(2+) technique. METHODS: Rats were randomized and cooled to 15  degrees C.
      Hearts were excised and perfusion-washed to remove extracellular calcium after
      0.5 h of hypothermia (n = 9), 4 h of hypothermia (n = 8), and after 4 h of
      hypothermia and 2 h rewarming (n = 9). A normothermic group, kept at 37  degrees
      C for 5 h, served as control (n = 6). [Ca(2+) ](i) was determined in perchloric
      acid extracts of heart tissue. Spontaneous cardiac electromechanic work was
      maintained during hypothermia without cardiac arrest or ischaemia. RESULTS:
      Between 0.5 and 4 h at 15  degrees C, a six-fold increase in cardiac [Ca(2+) ](i)
      was observed (0.55 +/- 0.10 vs. 2.93 +/- 0.76 MUmol (g dry wt)(-1) ). Rewarming
      resulted in a 33% decline in [Ca(2+) ](i) , but the actual value was
      significantly above the value measured in control hearts. CONCLUSION: We show
      that calcium overload is a characteristic feature of the beating heart during
      deep hypothermia, which aggravates by increasing duration of exposure. The
      relatively low decline in [Ca(2+) ](i) during the rewarming period indicates
      difficulties in recovering calcium homoeostasis, which in turn may explain
      cardiac contractile dysfunction observed after rewarming.

PMID- 22950549
TI  - Culture-based and denaturing gradient gel electrophoresis analysis of the
      bacterial community from Chungkookjang, a traditional Korean fermented soybean
      food.
AB  - The bacterial community of Chungkookjang and raw rice-straw collected from
      various areas in South Korea was investigated using both culture-dependent and
      culture-independent methods. Pure cultures were isolated from Chungkookjang and
      raw rice-straw on tryptic soy agar plates with 72 to 121 colonies and identified
      by 16S rDNA gene sequence analysis, respectively. The traditional culture-based
      method and denaturing gradient gel electrophoresis analysis of PCR-amplified 16S
      rDNA confirmed that Pantoea agglomerans and B. subtilis were identified as
      predominant in the raw rice-straw and Chungkookjang, respectively, from Iljuk
      district of Gyeonggi province, P. ananatis and B. licheniformis were identified
      as predominant in the raw rice-straw and Chungkookjang from Wonju district of
      Gangwon province, and Microbacterium sp. and B. licheniformis were identified as
      predominant in the raw rice-straw and Chungkookjang from Sunchang district of
      Jeolla province. Other strains, such as Bacillus, Enterococcus, Pseudomonas,
      Rhodococcus, and uncultured bacteria were also present in raw rice-straw and
      Chungkookjang. PRACTICAL APPLICATION: A comprehensive analysis of these
      microorganisms would provide a more detailed understanding of the biologically
      active components of Chungkookjang and help improve its quality. Polymerase chain
      reaction-denaturing gradient gel electrophoresis analysis can be successfully
      applied to a fermented food to detect unculturable or more species than the
      culture-dependent method. This technique is an effective and convenient culture
      independent method for studying the bacterial community in Chungkookjang. In this
      study, the bacterial community of Chungkookjang collected from various areas in
      South Korea was investigated using both culture-dependent and culture-independent
      methods.

PMID- 22950550
TI  - The science of prescribing.

PMID- 22950551
TI  - Balanced prescribing - principles and challenges.
AB  - Balanced prescribing is a process that recommends a medicine appropriate to the
      patient's condition and, within the limits created by the uncertainty that
      attends therapeutic decisions, a dosage regimen that optimizes the balance of
      benefit to harm. The essential steps in achieving this are (a) careful attention
      to the history, examination, and investigation of the patient's condition and
      drug therapy, (b) accurate diagnosis, (c) detailed attention to prescribing the
      dosage regimen in the light of the therapeutic goal, (d) careful writing of the
      prescription and (e) regular monitoring of therapy, including attention to
      beneficial outcomes, adverse reactions, and patient adherence. The two major
      requirements in determining the dosage regimen are (1) understanding the
      pathophysiology of a health problem and matching it to the mechanisms of action
      of the relevant medicines and (2) assessing the benefit to harm balance of the
      therapy, although the difficulties in doing this in the individual are great.
      Major challenges in prescribing include provision of adequate education for all
      prescribers early in their undergraduate training and maintaining their expertise
      after graduation, obtaining evidence to inform appropriate monitoring of therapy,
      reducing the incidence of medication errors, and providing high quality
      information that will at the same time guide prescribing decisions and be
      sufficiently flexible to allow prescribers to tailor therapy to the needs of the
      individual patient. Careful attention to all facets of prescribing can improve
      the chances of benefit, reduce the risks of adverse reactions and interactions,
      and enhance adherence to therapy.

PMID- 22950553
TI  - Time-of-flight secondary ion mass spectrometry-based molecular distribution
      distinguishing healthy and osteoarthritic human cartilage.
AB  - Osteoarthritis (OA) is a pathology that ultimately causes joint destruction. The
      cartilage is one of the principal affected tissues. Alterations in the lipid
      mediators and an imbalance in the metabolism of cells that form the cartilage
      (chondrocytes) have been described as contributors to the OA development. In this
      study, we have studied the distribution of lipids and chemical elements in
      healthy and OA human cartilage. Time of flight-secondary ion mass spectrometry
      (TOF-SIMS) allows us to study the spatial distribution of molecules at a high
      resolution on a tissue section. TOF-SIMS revealed a specific peak profile that
      distinguishes healthy from OA cartilages. The spatial distribution of cholesterol
      related peaks exhibited a remarkable difference between healthy and OA
      cartilages. A distinctive colocalization of cholesterol and other lipids in the
      superficial area of the cartilage was found. A higher intensity of oleic acid and
      other fatty acids in the OA cartilages exhibited a similar localization. On the
      other hand, CN(-) was observed with a higher intensity in the healthy samples.
      Finally, we observed an accumulation of calcium and phosphate ions exclusively in
      areas surrounding the chondrocyte in OA tissues. To our knowledge, this is the
      first time that TOF-SIMS revealed combined changes in the molecular distribution
      in the OA human cartilage.

PMID- 22950554
TI  - Traffic air pollution and mortality from cardiovascular disease and all causes: a
      Danish cohort study.
AB  - BACKGROUND: Traffic air pollution has been linked to cardiovascular mortality,
      which might be due to co-exposure to road traffic noise. Further, personal and
      lifestyle characteristics might modify any association. METHODS: We followed up
      52 061 participants in a Danish cohort for mortality in the nationwide Register
      of Causes of Death, from enrollment in 1993-1997 through 2009, and traced their
      residential addresses from 1971 onwards in the Central Population Registry. We
      used dispersion-modelled concentration of nitrogen dioxide (NO2) since 1971 as
      indicator of traffic air pollution and used Cox regression models to estimate
      mortality rate ratios (MRRs) with adjustment for potential confounders. RESULTS:
      Mean levels of NO2 at the residence since 1971 were significantly associated with
      mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI],
      1.06-1.51, per doubling of NO2 concentration) and all causes (MRR, 1.13; 95% CI,
      1.04-1.23, per doubling of NO2 concentration) after adjustment for potential
      confounders. For participants who ate < 200 g of fruit and vegetables per day,
      the MRR was 1.45 (95% CI, 1.13-1.87) for mortality from cardiovascular disease
      and 1.25 (95% CI, 1.11-1.42) for mortality from all causes. CONCLUSIONS: Traffic
      air pollution is associated with mortality from cardiovascular diseases and all
      causes, after adjustment for traffic noise. The association was strongest for
      people with a low fruit and vegetable intake.

PMID- 22950555
TI  - Classification of vascular disorders in the skin and selected data on new
      evaluation and treatment.
AB  - Cutaneous vascular disorders are common. They include arteries, veins, and
      lymphatic vessels, or a mixture of them. In this review, we discuss
      classification, new developments in understanding and treatment of vascular
      diseases. We focus on infantile hemangiomas and drug therapy, vasculitides with
      new vasculitic syndromes, yellow nail syndrome and localized lymphatic
      malformations. Benign cutaneous vascular lesions may be a sign of severe internal
      diseases. In many cases multidisciplinary treatment is important. The
      dermatologist can often act as a pilot for these patients.

PMID- 22950556
TI  - Dermoscopy, confocal laser microscopy, and hi-tech evaluation of vascular skin
      lesions: diagnostic and therapeutic perspectives.
AB  - Vascular skin lesions comprise a wide and heterogeneous group of malformations
      and tumors that can be correctly diagnosed based on natural history and physical
      examination. However, considering the high incidence of such lesions, a great
      number of them can be misdiagnosed. In addition, it is not so rare that an
      aggressive amelanotic melanoma can be misdiagnosed as a vascular lesion. In this
      regard, dermoscopy and confocal laser microscopy examination can play a central
      role in increasing the specificity of the diagnosis of such lesions. In fact, the
      superiority of these tools over clinical examination has encouraged
      dermatologists to adopt these devices for routine clinical practice, with a
      progressive spread of their use. In this review, we will go through the
      dermoscopic and the confocal laser microscopy of diagnosis of most frequent
      vascular lesions (i.e., hemangiomas angiokeratoma, pyogenic granuloma,
      angiosarcoma) taking into particular consideration the differential diagnosis
      with amelanotic melanoma.

PMID- 22950557
TI  - Management of leg ulcers in patients with chronic venous insufficiency: the
      experience of a Dermatology Clinic in Bucharest, Romania.
AB  - Venous ulcers are the most severe skin manifestation of chronic venous
      insufficiency. Treatment is complex and it is performed according to the stage of
      the disease. It includes changes of lifestyle, compressive therapy, phlebotropic
      medication, topical therapy of the ulcer, antibiotic therapy (topical and
      systemic), sclerotherapy, and surgical treatment. Patients with venous leg ulcers
      that attend the Second Dermatology Clinic of Colentina Clinical Hospital, are
      treated both as inpatients and as outpatients. They benefit from topical
      treatment and bandaging performed by specialized medical personnel in separate
      treatment room with strictly monitored conditions of asepsis and antisepsis. A
      follow-up study of these patients was made from January 1, 2009 to December 31,
      2011. The average age of patients was 65.9 years (+/- 14.2), most of them being
      in the eight decade of life (31.9%). In almost half of the cases (44.2%), the
      patients spent more than 1 week in the hospital. Bacteriological investigations
      from the ulcers were performed in 55.1% of patients and the most frequent
      infectious agents were found to be Staphylococcus aureus (26.3%) and Enterobacter
      spp. (17.2%). Treatment of leg ulcer patients proves to be a long and complex
      one, a systematic and organized approach being needed in order to obtain healing
      of the wound.

PMID- 22950558
TI  - Laser use in infantile hemangiomas, when and how.
AB  - Infantile hemangiomas (IHs) are proliferating embrional tumors which can stem
      from placented tissue and are constituted by endothelial cell hyperproliferation.
      The management of the IHs is always challenging for all the specialists because
      of the heterogeneous behavior of these lesions. The factors leading to an
      aggressive position are essentially these: the prevention or reduction of
      aesthetic risks, the prevention or treatment of ulcerated hemangiomas, the
      prevention or impairment of functional risks and pain, and the removal of life
      threatening risks. The treatment of vascular lesions is one of the mostly sought
      and performed cutaneous laser procedures, and in the field of IH treatments the
      more used laser devices certainly are pulsed dye lasers. Early laser therapy is
      able to reduce the possibility that the lesion will reach its full size,
      preventing several complications, connected to the hemangioma's growth, and
      providing psychological relief for pediatric patients and their parents.

PMID- 22950559
TI  - Hemangiomas: new insight and medical treatment.
AB  - Infantile hemangiomas (IHs) are the most common tumors of infancy and are usually
      characterized by a pattern of rapid proliferation, followed by a slower period of
      involution. In most cases, IHs do not require any treatment because they
      spontaneously regress over the years. However, in a minority of patients, a
      therapy is mandatory and should be started early to avoid functional and esthetic
      impairment or even severe systemic complications. Currently, no medications exist
      that are specifically labeled to treat his; however, because the serendipitous
      discovery of the efficacy of propranolol in the treatment of IHs at the
      Dermatologic Department of the University of Bologna, beta-blocker therapy has
      become the first-line therapy in severe and/or complicated hemangiomas. This is a
      practical review reporting our approach to IHs in our daily practice.

PMID- 22950560
TI  - Cutaneous necrotizing vasculitis: a rational therapeutic approach.
AB  - Cutaneous necrotizing vasculitis is a heterogeneous group of disorders
      characterized clinically by palpable purpura, and histologically by a segmental
      angiocentric inflammatory condition with fibrinoid necrosis of the vessel wall,
      endothelial swelling, and nuclear dust of the post capillary venules. Often, the
      skin seems the only organ apparently damaged, but systemic involvement may occur.
      In up to 60% of cases of cutaneous necrotizing vasculitis, the cause remains
      unknown; in others, it may be due to a variety of underlying conditions such as
      drugs, chemicals, food allergens, infections, chronic inflammatory systemic
      disorders, or malignant neoplasms. A rational therapeutic approach of vasculitis
      begins with the identification and stoppage of any suspected underlying
      condition. This may be all that is required for the treatment, because it is
      usually followed by the clearing of cutaneous lesions, and systemic signs and
      symptoms. In other cases, local and/or systemic anti-inflammatory and/or
      immunosuppressive therapy is recommended.

PMID- 22950561
TI  - Laser use for cutaneous vascular alterations of cosmetic interest.
AB  - In 1983, selective photothermolysis dramatically transformed vascular surgery,
      reducing the adverse effects and increasing its efficacy. As a result, laser
      surgery is now considered the gold standard treatment for many congenital and
      acquired skin vascular disorders. In this paper, the authors analyze the main
      laser sources for vascular surgery, the general parameters regarding laser-tissue
      interactions that can influence the treatment (such as hemodynamic features,
      anatomical areas, vessel depth, and diameters), and other aspects important for a
      good laser practice. Afterward, the main indications for laser treatment in
      vascular cutaneous disorders are discussed, with particular reference to port
      wine stain, hemangioma, facial telangiectasia, rosacea, spider angioma, venous
      lake, varicose leg veins, and leg telangiectasias.

PMID- 22950562
TI  - Management of lymphedema.
AB  - The basic principle of the management of lymphedema is so called complex
      decongestive physical therapy. This therapy is divided into two phases: (i) edema
      reduction phase--an initial intensive treatment phase aiming for limb volume
      reduction; and (ii) maintenance phase--following long-term phase to sustain a
      manageable limb volume. The first phase consists of a number of physical
      therapeutic approaches which are: manual lymph drainage, pneumatic pump drainage,
      low-stretch bandaging, exercises, and skin care. Long-term maintenance phase
      consists of self-lymph drainage, low-stretch bandaging, or compressive garments,
      and sometimes when indicated pneumatic pump drainage, exercises, and skin care.

PMID- 22950563
TI  - Cutaneous vascular lesions and their management in Indian setting.
AB  - Indian skin with its broad range of skin color and complexion differs in the
      presentation and management of cutaneous vascular lesions. Common congenital and
      acquired vascular lesions are discussed with respect to the epidemiology,
      clinical presentation, and management strategies in an Indian setting. An effort
      has been made to review Indian case reports and studies of cutaneous vascular
      lesions, potential possible modification in the conventional treatment
      considering resource constraints, cultural practices, availability and cost
      effectiveness of the laser and light sources, camouflage techniques, and
      sclerotherapy. The review concludes with emphasis on the need of availability of
      cost-effective, quality equipment customized to Indian skin and quality studies
      and trials for the management of cutaneous vascular lesions in an Indian setting.

PMID- 22950564
TI  - Paradoxical effect of infliximab in a patient with hidradenitis suppurativa.

PMID- 22950565
TI  - Mizoribine treatment for antihistamine-resistant chronic autoimmune urticaria.
AB  - Chronic autoimmune urticaria is routinely diagnosed using an autologous serum
      skin test. Mizoribine is a newly developed immunosuppressive agent that has low
      toxicity. The pharmacological effects of mizoribine are similar to those of
      another purine biosynthesis inhibitor, mycophenolate mofetil. A 57-year-old woman
      presented with recurrent wheals and was insufficiently managed with
      administration of antihistamines, antileukotrienes, oral corticosteroids, and
      cyclosporine. She was positive in the autologous serum skin test. Oral mizoribine
      therapy was started as a combination therapy with prednisolone. The patient
      achieved a dramatic improvement in symptoms and complete resolution of the
      urticaria a few days after adding mizoribine to her treatment. The prednisolone
      was tapered after the start of mizoribine treatment. Her symptoms did not flare
      up, and no side effects were observed. In vitro basophil histamine release assays
      suggested that she might have anti-IgE autoantibody-type histamine release
      activity. We believe that mizoribine has a therapeutic role in some patients with
      chronic autoimmune urticaria and may be useful for treatment of cases not
      responsive to classical therapy. We suggest that mizoribine might help to reduce
      anti-IgE autoantibody acting on the surface of basophils in chronic autoimmune
      urticaria.

PMID- 22950566
TI  - Therapeutic effect of mizoribine on pemphigus vulgaris and pemphigus foliaceus.
AB  - We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive
      agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and
      pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and
      three pemphigus foliaceus) received the combination therapy of prednisolone and
      mizoribine. Complete remission was observed in three of the eight patients with
      pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The
      four patients with complete remission had a rapid clinical response and achieved
      remission at a median of 11.8 months. Partial remission was achieved in two of
      the three patients with pemphigus foliaceus. The median time to achieve partial
      remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had
      complete or partial remission and were able to taper their prednisolone. The
      cumulative probability of having a complete remission was 64.3% at 19 months of
      follow-up using Kaplan-Meier analysis. The effectiveness of the additional
      mizoribine therapy could be attributed to its corticosteroid-sparing properties
      as well as its immunosuppressive effects. The serum concentration titer of
      mizoribine was around 1.0 MUg/mL 2 hours after administration. Patients who were
      not improved by the additional mizoribine might require a continuously higher
      dose of mizoribine to achieve effective therapy.

PMID- 22950567
TI  - Successful clearance of facial common warts by local hyperthermia: report of two
      cases.
AB  - Facial common wart is a disfiguring condition caused by human papilloma virus
      infection. Choices to treat facial warts should be cautious, in consideration of
      adverse cosmetic consequences. Two cases of facial common warts were treated by
      local hyperthermia at 44  degrees C for 30 minutes, once a day for three
      consecutive days (the first session), and similarly treated a week later for more
      2 days (second session). The warts completely disappeared in 10 and 12 weeks,
      respectively in the two patients. Adverse effect was tolerable burning sensation
      in the two patients and a temporary heat-induced blistering in one of them. This
      pioneer trial suggested that mild hyperthermia is a safe and effective method in
      treating facial common warts.

PMID- 22950569
TI  - All hands on dex.

PMID- 22950570
TI  - Modifications in connexin expression in liver development and cancer.
AB  - The establishment of an elaborate gap junctional intercellular communication
      network, especially between hepatocytes, is important for normal liver
      development. In fact, the production of the gap junction building blocks, the
      connexins, undergoes several well-defined changes throughout the hepatic
      differentiation process. This ultimately results in the acquisition of an adult
      connexin expression pattern which is critical for maintaining the fully
      differentiated hepatocyte-specific phenotype. Abnormalities of connexin
      production are observed in a number of pathological conditions, such as during
      liver cancer. This article provides an overview of these processes with emphasis
      on the underlying molecular mechanisms.

PMID- 22950571
TI  - Stress is dominant in patients with depression and chronic low back pain. A
      qualitative study of psychotherapeutic interventions for patients with non
      specific low back pain of 3-12 months' duration.
AB  - BACKGROUND: There is continuing uncertainty in back pain research as to which
      treatment is best suited to patients with non-specific chronic low back pain
      (CLBP). In this study, Gestalt therapy and the shock trauma method Somatic
      Experiencing(r) (SE) were used as interventions in parallel with the usual cross
      disciplinary approach. The aim was to investigate how these treatments influence
      a patient's capacity to cope with CLBP when it is coupled with depression.
      METHODS: In this qualitative explorative study, a phenomenological-hermeneutic
      framework was adopted. Patients were recruited on the basis of following
      criteria: A moderate depression score of 23-30 according to the Beck Depression
      Inventory Scale and a pain score of 7-10 (Box scale from 0-10) and attendance at
      five- six psychotherapeutic sessions. Six patients participated in the study. The
      data was comprised of written field notes from each session, which were
      subsequently analysed and interpreted at three levels: naive reading, structural
      analysis and critical interpretation and discussion. RESULTS: Three areas of
      focus emerged: the significance of previous experiences, restrictions in everyday
      life and restoration of inner resources during the therapy period. The study
      revealed a diversity of psychological stressors that related to loss and sorrow,
      being let down, violations, traumatic events and reduced functioning, which led
      to displays of distress, powerlessness, reduced self-worth, anxiety and
      discomfort.Overall, the sum of the stressors together with pain and depression
      were shown to trigger stress symptoms. Stress was down-played in the
      psychotherapeutic treatment and inner resources were re-established, which
      manifested as increased relaxation, presence, self-worth, sense of responsibility
      and happiness. This, in turn, assisted the patients to better manage their CLBP.
      CONCLUSIONS: CLBP is a stress factor in itself but when coupled with depression,
      they can be regarded as two symptom complexes that mutually affect each other in
      negative ways. When pain, stress and depression become overwhelming and there are
      few internal resources available, stress seems to become prominent. In this
      study, Gestalt therapy and the SE-method may have helped to lower the six
      patients' level of stress and restore their own internal resources, thereby
      increasing their capacity to cope with their CLBP.

PMID- 22950572
TI  - Major barriers against renin-angiotensin-aldosterone system blocker use in
      chronic kidney disease stages 3-5 in clinical practice: a safety concern?
AB  - Renin-angiotensin-aldosterone system (RAAS) blockers are underutilized in
      patients with chronic kidney disease (CKD). We aimed to determine barriers
      against the use of RAAS blockers in these patients. Patients with stage 3-5 CKD
      referred to Hacettepe University Hospital Nephrology Unit during a 1 year period
      were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166
      male, 113 female) were analyzed. The mean age of the patients was 56.7 +/- 15.2
      years, mean serum creatinine was 2.45 +/- 1.44 mg/dL, and mean glomerular
      filtration rate was 33.3 +/- 15.1 mL/min. The mean follow-up time was 22.0 +/-
      21.9 months and the clinical visit number was 4.0 +/- 3.5. Angiotensin-converting
      enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all
      patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of
      patients, RAAS blockers had either been used earlier or were being used.
      Hyperkalemia was the principal reason for both not starting and also
      discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for
      not starting RAAS blockers were unclear. This study showed that hyperkalemia is
      the major barrier against the use of RAAS blockers in patients with CKD. There
      was, however, a subset of patients who did not receive RAAS blockers even without
      clear contraindications.

PMID- 22950573
TI  - Copper(I)-catalyzed formal carboboration of alkynes: synthesis of tri- and
      tetrasubstituted vinylboronates.
AB  - The first copper-catalyzed formal carboboration of alkynes, in which a C-B bond
      and a C-C bond are created in a single catalytic cycle, is presented. The
      reaction proceeds with high regioselectivity and syn-stereoselectivity to form
      tri- and tetrasubstituted vinylboronic esters from commercially available
      bis(pinacolato)diboron. A subsequent cross-coupling reaction gives access to
      highly substituted alkenes.

PMID- 22950574
TI  - A guide to reporting studies in rural and remote health.

PMID- 22950575
TI  - Effects of heat treatment on the carotenoid and tocopherol composition of tomato.
AB  - The objective of this study was to determine the influence of thermal processing
      on the assessment of tocopherols and carotenoids, as well as their isomer
      formation in tomatoes. The sliced tomatoes were heated in an oven at 100, 130,
      and 160  degrees C for 5, 10, and 20 min, then freeze-dried. Freeze-dried samples
      were finely ground and the analysis was performed on lyophilized samples. The
      average concentrations of total lycopene, lutein, beta-carotene, alpha
      tocopherol, and gamma-tocopherol in fresh tomatoes (in 100 g dry weight) were
      21.2, 1.1, 2.7, 8.0, and 2.5 mg, respectively. Oven baking of tomato at 160 
      degrees C for 20 min led to a significant increase in the apparent measurement of
      lycopene, beta-carotene, and alpha-tocopherol content by 75%, 81%, and 32%,
      respectively. Heating induced isomerization of (all-E) to various (Z) isomers of
      lycopene, and we found that the total (Z)-lycopene proportion in the tomatoes
      increased with longer heating time. (All-E)-lycopene constituted 75.4% in fresh
      tomatoes and decreased to 52.5% in oven-baked tomatoes (160  degrees C, 20 min),
      while (5Z)-lycopene increased from 9.4% to 17.9% of total lycopene. However, beta
      carotene release and isomerization was less influenced by the heat treatment than
      that of lycopene. These results suggested that thermal processes might break down
      cell walls and enhance the release of carotenoids and tocopherols from the
      matrix, as well as increase isomerization of lycopene and beta-carotene.

PMID- 22950576
TI  - Population genetic structure of the malaria vector Anopheles funestus, in a
      recently re-colonized area of the Senegal River basin and human-induced
      environmental changes.
AB  - BACKGROUND: Anopheles funestus is one of the major malaria vectors in tropical
      Africa. Because of several cycles of drought events that occurred during the
      1970s, this species had disappeared from many parts of sahelian Africa, including
      the Senegal River basin. However, this zone has been re-colonized during the last
      decade by An. funestus, following the implementation of two dams on the Senegal
      River. Previous studies in that area revealed heterogeneity at the biological and
      chromosomal level among these recent populations. METHODS: Here, we studied the
      genetic structure of the newly established mosquito populations using eleven
      microsatellite markers in four villages of the Senegal River basin and compared
      it to another An. funestus population located in the sudanian domain. RESULTS:
      Our results presume Hardy Weinberg equilibrium in each An. funestus population,
      suggesting a situation of panmixia. Moreover, no signal from bottleneck or
      population expansion was detected across populations. The tests of genetic
      differentiation between sites revealed a slight but significant division into
      three distinct genetic entities. Genetic distance between populations from the
      Senegal River basin and sudanian domain was correlated to geographical distance.
      In contrast, sub-division into the Senegal River basin was not correlated to
      geographic distance, rather to local adaptation. CONCLUSIONS: The high genetic
      diversity among populations from Senegal River basin coupled with no evidence of
      bottleneck and with a gene flow with southern population suggests that the re
      colonization was likely carried out by a massive and repeated stepping-stone
      dispersion starting from the neighboring areas where An. funestus endured.

PMID- 22950577
TI  - An un-commissioned randomized, placebo-controlled double-blind study to test the
      effect of deep sea fish oil as a pain reliever for dogs suffering from canine OA.
AB  - BACKGROUND: An un-commissioned randomized, double-blinded, placebo controlled
      clinical study was planned using a deep sea fish oil product for pets. Seventy
      seven client-owned dogs with osteoarthritis were randomly assigned to supplement
      the food with either the fish oil product or corn (=placebo) oil. Our main
      outcome variables were force platform variables peak vertical force (PVF) and
      impulse, the validated Helsinki Chronic Pain Index (HCPI) and the use of rescue
      NSAIDs. Secondary outcome variables were a locomotion visual analog scale (VAS),
      a Quality of life VAS, a comparative questionnaire, a veterinary assessment,
      owners' final assessment of outcome and guessing the product given. RESULTS: When
      comparing the two test groups at the end of the trial (16 weeks) there was no
      significant difference in any of the main outcome variables but owners of dogs
      that had taken fish oil were significantly happier with the treatment at the end
      visit and did significantly better at guessing what group their dogs had been in,
      compared to the placebo group. When comparing variables within the fish oil group
      as change from baseline to trial end, there were significant positive changes in
      PVF, HCPI, NSAID use, Quality of life VAS, as well as in all three scores in the
      comparative questionnaire (locomotion, every-day situations, and skin & coat).
      There were similar positive trends in force platform impulse and in the
      veterinary assessment variables, although they did not reach significance. Within
      the placebo group there were significant positive changes only in the HCPI and a
      significant deterioration according to veterinary assessment. CONCLUSIONS: When
      compared to placebo, there was not a major statistically significant benefit in
      using deep sea fish oil as a pain reliever in our study population of dogs
      suffering from osteoarthritis. However, the fish oil treated patients improved
      significantly in many of the variables, when comparing baseline values to the
      study-end values within the group, indicating a true but small relief in
      symptoms. Deep sea fish oil supplementation could be considered a part of the
      multimodal pain relieving approach currently recommended for dogs suffering from
      OA, especially for individuals that do not tolerate anti-inflammatory drugs.

PMID- 22950578
TI  - Vascularisation of myringo-/tympanoplastic grafts in active and inactive chronic
      mucosal otitis media: a prospective cohort study.
AB  - OBJECTIVES: To evaluate the vascularisation process of the grafted fascia or
      perichondrium in active and inactive chronic mucosal otitis media. DESIGN:
      Prospective study. SETTING: University-based, secondary referral hospital.
      PARTICIPANTS: Two hundred thirty-two patients who underwent type 1 tympanoplasty
      or myringoplasty by one experienced surgeon. MAIN OUTCOME MEASURES: After
      postoperative days 5-7, the graft was inspected using a binocular operating
      microscope at least twice weekly until vascularisation was confirmed to have
      commenced. This point was defined as the time of vascularisation. An intact graft
      at 3 months postoperatively was considered a closure success. RESULTS: The mean
      time of vascularisation of 232 grafts was 14.2 +/- 3.6 days (range 8-25). The
      vascularisation time differed according to the perforation size. The perforations
      involving 50% and less of the pars tensa were revascularised earlier than those
      involving 75% and more. There was no relationship between vascularisation time
      and closure success or failure. Age itself did not influence the vascularisation
      time or the risk of closure failure. Postoperative otorrhea was higher in
      patients with a preoperative wet middle ear mucosa than among those with a dry
      one. CONCLUSION: The vascularisation time was shorter in perforations of 50% and
      less than those of 75% and more but the rate of closure success was not different
      between two. The graft failure was not attributed to the failure of
      vascularisation. Age itself seemed not to be a contraindication for myringo
      /tympanoplasty in otherwise healthy elderly patients.

PMID- 22950579
TI  - Binary fluorous alkylation of biogenic primary amines with perfluorinated
      aldehyde followed by fluorous liquid chromatography-tandem mass spectrometry
      analysis.
AB  - We have developed a novel method for the determination of biogenic amines
      (dopamine, norepinephrine, 3-methoxytyramine, normetanephrine, serotonin,
      tyramine, tryptamine, 5-methoxytryptamine, and histamine) utilizing liquid
      chromatography with electrospray ionization tandem mass spectrometry (LC-ESI
      MS/MS) combined with a separation-oriented derivatization technique. Using this
      approach, primary amino groups in the target amines were selectively dialkylated
      with a perfluorinated aldehyde reagent (2H,2H,3H,3H-perfluoroundecan-1-al)
      through reductive amination. The derivatives were directly injected onto an LC
      column containing perfluoroalkyl-modified stationary phase and were separated via
      gradient elution using a water/methanol/trifluoroacetic acid mixture and
      trifluoroethanol with formic acid as mobile phases. Matrix-induced signal
      suppression effects were eliminated because the binary fluorous-labeled amines
      were strongly retained on the fluorous-phase LC column, whereas the nonfluorous
      derivatives, including matrix components and monofluorous-labeled compounds such
      as the derivatization reagent, were poorly retained under the separation
      conditions. The linear dynamic ranges of the target amines were established over
      a concentration range of 0.01-1 nM (r > 0.9978), and the limits of detection were
      found to be 7.8-26 amol on column. The feasibility of this method was further
      evaluated by applying it to human plasma samples.

PMID- 22950582
TI  - Cities, environmental stressors, ageing and chronic disease.

PMID- 22950583
TI  - Successful ageing: the case of Taiwan.
AB  - AIM: To investigate the conditions of successful ageing in Taiwan. METHODS: The
      respondents included two age groups, namely, 45-64 years (n = 1143), and 65 years
      and older (n = 1309), from a cross-section national representative survey
      conducted in 2007. RESULTS: Older people faced more problems that cause
      depression than their counterparts. Eleven per cent of older people were in the
      labour market. Neither middle-aged people nor older people were actively involved
      in volunteer services. Those who lived longer had less social support. Over 50%
      felt their financial preparations for later life were not adequate. Educational
      levels and family income were the significant factors affecting the levels of
      successful ageing. CONCLUSIONS: Improvement in the four dimensions of successful
      ageing must be re-emphasised for both age groups.

PMID- 22950580
TI  - Biomolecule gradient in micropatterned nanofibrous scaffold for spatiotemporal
      release.
AB  - Controlled molecule release from scaffolds can dramatically increase the scaffold
      ability of directing tissue regeneration in vitro and in vivo. Crucial to the
      regeneration is precise regulation over release direction and kinetics of
      multiple molecules (small genes, peptides, or larger proteins). To this end, we
      developed gradient micropatterns of electrospun nanofibers along the scaffold
      thickness through programming the deposition of heterogeneous nanofibers of
      poly(epsilon-caprolactone) (PCL) and poly(D,L-lactide-co-glycolide) acid (PLGA).
      Confocal images of the scaffolds containing fluorophore-impregnated nanofibers
      demonstrated close matching of actual and designed gradient fiber patterns;
      thermal analyses further showed their matching in the composition. Using acid
      terminated PLGA (PLGAac) and ester-terminated PLGA (PLGAes) to impregnate
      molecules in the PCL-PLGA scaffolds, we demonstrated for the first time their
      differences in nanofiber degeneration and molecular weight change during
      degradation. PLGAac nanofibers were more stable with gradual and steady increase
      in the fiber diameter during degradation, resulting in more spatially confined
      molecule delivery from PCL-PLGA scaffolds. Thus, patterns of PCL-PLGAac
      nanofibers were used to design versatile controlled delivery scaffolds. To test
      the hypothesis that molecule-impregnated PLGAac in the gradient-patterned PCL
      PLGAac scaffolds can program various modalities of molecule release, model
      molecules, including small fluorophores and larger proteins, were respectively
      used for time-lapse release studies. Gradient-patterns were used as building
      blocks in the scaffolds to program simultaneous release of one or multiple
      proteins to one side or, respectively, to the opposite sides of scaffolds for up
      to 50 days. Results showed that the separation efficiency of molecule delivery
      from all the scaffolds with a thickness of 200 MUm achieved >88% for proteins and
      >82% for small molecules. In addition to versatile spatially controlled delivery,
      micropatterns were designed to program sequential release of proteins. The
      hierarchically structured materials presented here may enable development of
      novel multifunctional scaffolds with defined 3D dynamic microenvironments for
      tissue regeneration.

PMID- 22950584
TI  - Cities, environmental stressors, ageing and chronic disease.
AB  - AIM: This study attempts to identify any association between length of exposure
      to urban environmental risk and non-infectious chronic disease in a group of
      Australian residents who lived in the same location for at least 20 years.
      METHODS: Using Australian survey data, we selected 1256 participants who were 45
      years and older and had lived in the same location for at least 20 years. We used
      logistic regression and survival analysis to identify factors associated with the
      presence of non-infectious chronic disease at baseline and after 7 years.
      RESULTS: Results show that increasing age, living in an urban area and living in
      an area with a lower socioeconomic status increase the odds of having a long-term
      health condition. CONCLUSION: This study provides empirical evidence that older
      long-term Australian urban residents are more likely to have a non-infectious
      chronic disease, which may be associated with environmental exposure, than those
      living in rural locations.

PMID- 22950585
TI  - Health education programs may be as effective as exercise intervention on
      improving health-related quality of life among Japanese people over 65 years.
AB  - AIM: The current study was aimed to examine the short-term effects of a 3-month
      health education program on health-related quality of life using the Short-Form
      36. METHODS: Twenty-five Japanese older people aged 65 and older in the health
      education program were compared with two historical control groups (n = 25 each)
      undertaking group and resistance exercise interventions and matched by age, sex
      and body mass index. A series of split-design two-way analyses of variance were
      conducted for data analysis. RESULTS: Significant improvements were observed in
      general health and vitality subscales of the Short-Form 36 in the educational
      program group. Multivariate analyses, adjusted for several confounding factors,
      revealed that the effects of the three programs were comparable. CONCLUSIONS: The
      findings suggest that a structured 3-month educational program may be as
      effective as exercise interventions in improving general health and vitality in a
      community-dwelling Japanese older population.

PMID- 22950586
TI  - Validation of the Environmental Audit Tool in both purpose-built and non-purpose
      built dementia care settings.
AB  - AIM: To provide further validation of the Environmental Audit Tool (EAT) by
      describing data on scores from 56 facilities and comparing the scores of
      facilities with a purpose-built dementia environment with those with non-purpose
      built designs. METHODS: Fifty-six facilities were assessed with the EAT. EAT
      scores for 24 purpose-built environments were compared with 32 non-purpose-built
      environments using a Wilcoxon rank-sum test. RESULTS: Descriptive data on EAT
      scores are presented across all facilities. Facilities scored well on
      safety/security, familiarity, highlighting useful stimuli and privacy. Purpose
      built unit scores were significantly higher than those for non-purpose-built
      environments for nine of 10 subscales of the EAT and the overall EAT score.
      CONCLUSION: The EAT can assess the quality of homelike environments in
      residential aged care facilities for people with dementia, differentiate between
      the quality of design in various types of facilities and provide an evidence
      basis for devising improvements.

PMID- 22950587
TI  - Adherence, persistence and continuation with cholinesterase inhibitors in
      Alzheimer's disease.
AB  - AIM: To determine adherence, persistence and continuation beyond 6 months with
      cholinesterase inhibitors in Australians with Alzheimer's disease. METHODS:
      Adherence and persistence with cholinesterase inhibitors were assessed by data
      linkage using the Pharmaceutical Benefits Scheme (PBS) Authority database and
      other health databases. RESULTS: Over 18 000 people commenced cholinesterase
      inhibitors during 2004. Adherence was 79.4% while the medication possession ratio
      was 0.88. Some 70.3% of people filled all six scripts for the initial trial
      period of therapy. Some 57.3% of evaluable patients accessed funding beyond six
      prescriptions, indicating that their clinicians had declared that there was a two
      point or more greater improvement in the Mini-Mental State Examination. Despite
      the high rate of continuation beyond 6 months, the rates of institutionalisation
      and death were no different to those reported in clinical trials. CONCLUSIONS:
      Persistence and adherence with cholinesterase inhibitors was reasonable once
      treatment was established. There was an unexpectedly high continuation rate
      beyond six prescriptions.

PMID- 22950588
TI  - Ageing in place: implications of morbidity patterns among older persons--findings
      from a cross-sectional study in a developing country (Jamaica).
AB  - AIM: This paper describes morbidity patterns among older people, relevant health
      care resources in a localised population in a developing country (Jamaica) and
      implications for ageing in place in the community. METHODS: Local morbidity
      patterns among older people were determined in Jamaica from a 2007 cross
      sectional study involving record searches at major hospitals and clinics. Age
      specific morbidity distributions were compiled. Data on health-care staff
      complement were also collected. RESULTS: Non-communicable diseases predominate in
      older people in Jamaica; 50% of diagnoses related to cardiovascular disorders and
      diabetes. Staff-to-population ratios were low compared with other international
      data. CONCLUSION: A high prevalence of non-communicable disease coupled with
      inadequate staffing threatens the likelihood of ageing in place in the Jamaican
      community. Secondary prevention efforts and social support services which enhance
      ageing in place are needed.

PMID- 22950589
TI  - Recruitment strategies for an osteoporosis clinical trial: analysis of
      effectiveness.
AB  - AIM: To examine the effectiveness of a planned rapid recruitment strategy in an
      osteoporosis clinical trial. METHODS: Multiple recruitment methods were explored,
      including media advertising, searching bone density scan and X-ray results in
      specialist and primary practice databases, community initiatives, and generation
      of research centre and study-specific pamphlets. RESULTS: Of 246 women screened,
      41 consenting to the study, only 14 were randomised. Thus, 232 (94%) volunteers
      were screen failures, ineligible or declined to participate. With regard to the
      cost-effectiveness of all recruitment strategies, searching the research centre
      database was the most successful, with four women randomised at a cost of
      approximately NZ$302 per volunteer. Other strategies were less cost-effective.
      CONCLUSION: Obtaining a specific study cohort can be achieved by a comprehensive,
      targeted, rapid recruitment program. A research centre database search was the
      most successful and cost-effective recruitment modality in this small study.

PMID- 22950590
TI  - Transportation behaviours of older adults: an investigation into car dependency
      in urban Australia.
AB  - AIM: Increased car dependency among Australia's ageing population may result in
      increased social isolation and other health impacts associated with the cessation
      of driving. While public transport represents an alternative to car usage,
      patronage remains low among older cohorts. This study investigates the
      facilitators and barriers to public transport patronage and the nature of car
      dependence among older Australians. METHODS: Data were gathered from a sample of
      24 adults (mean age = 70 years) through a combination of quantitative (remote
      behavioural observation) and qualitative (interviews) investigation. RESULTS:
      Findings suggest that relative convenience, affordability and health/mobility may
      dictate transport mode choices. The car is considered more convenient for the
      majority of suburban trips irrespective of the availability of public transport.
      CONCLUSION: Policy attention should focus on providing better education and
      information regarding driving cessation and addressing older age specific social
      aspects of public transport including health and mobility issues.

PMID- 22950591
TI  - Randomised controlled pilot study in Japan comparing a home visit program using a
      Functioning Improvement Tool with a home visit with conversation alone.
AB  - AIM: This study aimed to determine the effect of a home visit program using a
      Functioning Improvement Tool (FIT) compared with a home visit using conversation
      alone. METHODS: Twenty-eight participants (mean age, 78.6 +/- 7.5 years) were
      randomly assigned to an intervention (n = 13) or control (n = 15) group for 3
      months. The intervention group received a 60-minute FIT home visit program; the
      control group received a 30-minute home visit using common conversational
      techniques. Measures were Mini-Mental State Examination, Frontal Assessment
      Battery (FAB) and Geriatric Depression Scale. RESULTS: The FAB score was
      significantly improved in the intervention group compared with the control group
      (2.5 vs -0.5, P = 0.02). CONCLUSIONS: Our FIT home visit program improved
      cognitive function. Further studies with larger samples and longer follow-up
      periods are needed to assess the long-term effectiveness of a FIT home visit
      program on cognition.

PMID- 22950592
TI  - Characteristics of older and younger patients with suspected paracetamol
      toxicity.
AB  - AIM: The aim of this study was to compare the characteristics of older and
      younger patients with suspected paracetamol toxicity. METHODS: A retrospective
      audit of the medical records of older (>=65 years, n = 25) and younger (20-30
      years, n = 50) patients with a detectable paracetamol level at a Sydney hospital.
      RESULTS: Older patients showed a different clinical pattern of suspected
      paracetamol toxicity and were more likely than younger patients to have
      multifactorial elevation of liver function tests. Additionally, older age was
      more likely to be associated with chronic therapeutic paracetamol dosing (71%
      older, 6% younger, P < 0.001), or with accidental toxic exposure (90% older, 29%
      younger, P < 0.001), while younger patients were more likely to have a deliberate
      high-dose exposure (10% older, 71% younger, P < 0.001). CONCLUSIONS: The age
      related differences in paracetamol exposure, paracetamol levels and liver
      function tests described in this population should be considered when ordering
      and interpreting paracetamol levels.

PMID- 22950593
TI  - Socioeconomic, psychological and demographic determinants of Australian baby
      boomers' financial planning for retirement.
AB  - AIM: Research from around the Western World has shown that psychological,
      socioeconomic and demographic factors can influence levels of financial planning.
      This study aims to determine how these factors interrelate to predict planning
      outcomes. METHOD: Data from the Ageing Baby Boomers in Australia Study were used
      to examine the effects of multiple factors on financial planning for 709 employed
      Australians nearing retirement. RESULTS: The results showed that higher income,
      future time perspective (FTP) and financial knowledge independently predicted
      levels of retirement planning. The effects of FTP and financial knowledge on
      financial planning were consistent across levels of socioeconomic status.
      CONCLUSIONS: While similar issues in financial planning appeared across
      socioeconomic status, a 'one size fits all' approach to retirement policy may not
      be effective. Instead, policy should be targeted towards the diverse needs of
      different groups. Raising public awareness of FTP and financial knowledge may
      provide a useful starting point.

PMID- 22950594
TI  - Neuropsychiatric effects of Parkinson's disease treatment.
AB  - Advances in the treatment of Parkinson's disease have led to significant
      improvement in many of the disabling motor symptoms of the disease, but often at
      the cost of neuropsychiatric side-effects. These include psychosis, dopamine
      dysregulation syndrome, impulse control disorders, mood disorders and Parkinson's
      disease drug withdrawal syndromes. Such side-effects can be as disabling and have
      as much impact on activities of daily living, quality of life, relationships and
      caregiver burden as motor symptoms. Awareness of these potential side-effects is
      important both in terms of obtaining informed consent, and to aid early
      identification and intervention, as patients may not spontaneously report side
      effects because of lack of insight, or deny them out of shame or embarrassment.
      The challenge of treatment can be a trade off between the emergence of such side
      effects and the amelioration of parkinsonism, best mastered with an informed
      dialogue between clinician and patient.

PMID- 22950595
TI  - The relationship between microalbuminuria, left ventricular hypertrophy,
      retinopathy, and sex hormone status in newly diagnosed hypertensive women.
AB  - An increased incidence of hypertension (HT) in postmenopausal female population
      has been shown in previous studies and this has been ascribed to an association
      with altered status of estrogen (E2) and other female sex hormones. Hypertension
      is associated with certain target organ damage (TOD) and related clinical
      conditions. The aim of this study was to determine the relationship between
      microalbuminuria, left ventricular hypertrophy (LVH), retinopathy, and sex
      hormone status in newly diagnosed hypertensive women. A total of 66 hypertensive
      women (39 postmenopausal and 27 premenopausal) were included in the study. Along
      with the tests recommended in the HT guidelines, LVH, hypertensive retinopathy,
      and microalbuminuria were investigated in all the patients. Sex hormones
      (follicle stimulating hormone, luteinizing hormone, progesterone, and E2) of the
      patients were also measured. The results show that there was no statistically
      significant difference between the two groups in regard to TOD except
      microalbuminuria. The frequency of microalbuminuria in premenopausal group
      patients was higher than that of the postmenopausal group patients (P = .038).
      This study suggests that TOD caused by HT is a very important health problem,
      seeming to be related with female sex hormones. 

PMID- 22950596
TI  - Health-related quality of life in patients with dual diagnosis: clinical
      correlates.
AB  - BACKGROUND: Although the studies published so far have found an affectation in
      the Health Related Quality of Life (HRQOL) in both psychiatric and substance use
      dependence disorders, very few studies have applied HRQOL as an assessment
      measure in patients suffering both comorbid conditions, or Dual Diagnosis. The
      aim of the current study was to assess HRQOL in a group of patients with Dual
      Diagnosis compared to two other non-comorbid groups and to determine what
      clinical factors are related to HRQOL. METHODS: Cross-sectional assessment of
      three experimental groups was made through the Short Form - 36 Item Health Survey
      (SF-36). The sample consisted of a group with Dual Diagnosis (DD; N = 35), one
      with Severe Mental Illness alone (SMI; N = 35) and another one with Substance Use
      Dependence alone (SUD; N = 35). The sample was composed only by males. To assess
      the clinical correlates of SF-36 HRQOL, lineal regression analyses were carried
      out. RESULTS: The DD group showed lower scores in most of the subscales, and in
      the mental health domain. The group with SUD showed in general a better state in
      the HRQOL while the group with SMI held an intermediate position with respect to
      the other two groups. Daily medication, suicidal attempts and daily number of
      coffees were significantly associated to HRQOL, especially in the DD group.
      CONCLUSIONS: The DD group showed lower self-reported mental health quality of
      life. Assessment of HRQOL in dual patients allows to identify specific needs in
      this population, and may help to establish therapeutic goals to improve
      interventions.

PMID- 22950597
TI  - Proposal of a histopathological predictive rule for the differential diagnosis
      between American tegumentary leishmaniasis and sporotrichosis skin lesions.
AB  - BACKGROUND: American tegumentary leishmaniasis (ATL) and sporotrichosis exhibit
      similar histopathology and low frequencies of microorganism detection.
      OBJECTIVES: This study seeks to identify microscopic alterations that can
      distinguish between these diseases. METHODS: Haematoxylin and eosin stained
      slides of 171 ATL and 97 sporotrichosis samples from active cutaneous lesions
      were examined for histopathological alterations. The lesions were diagnosed by
      isolating the agent (which was not visible) in culture. An intuitive diagnosis
      was assigned to each slide. The strength of the association between the
      histopathological findings and the diagnosis was estimated by an odds ratio, and
      each finding was graded according to a regression model. A score was assigned to
      each sample based on the histopathological findings. A study of the interobserver
      reliability was performed by calculating kappa coefficients of the
      histopathological findings and intuitive diagnoses. RESULTS: The markers
      'macrophage concentration', 'tuberculoid granuloma' and 'extracellular matrix
      degeneration' were associated with ATL. 'Suppurative granuloma', 'stellate
      granuloma', 'different types of giant cells', 'granulomas in granulation tissue'
      and 'abscess outside the granuloma' were associated with a diagnosis of
      sporotrichosis. 'Macrophage concentration' and 'suppurative granuloma' had the
      highest (substantial and almost perfect, respectively) reliability. The
      regression model score indicated 92.0% accuracy. The intuitive diagnosis had
      82.5% diagnostic accuracy and substantial reliability. CONCLUSIONS: Taking into
      account the clinical and epidemiological context, some histopathological
      alterations might be useful for the differential diagnosis between ATL and
      sporotrichosis cutaneous lesions in cases in which the aetiological agent is not
      visible.

PMID- 22950598
TI  - Highly efficient blue electrophosphorescent polymers with fluorinated
      poly(arylene ether phosphine oxide) as Backbone.
AB  - In view of the tolerance of F atoms in FIrpic to the nucleophilic aromatic
      substitution polymerization, an activated fluorinated poly(arylene ether
      phosphine oxide) backbone is used to construct novel blue electrophosphorescent
      polymers containing FIrpic as the blue emitter, because they can be synthesized
      under a milder temperature of 120  degrees C. Compared with the counterparts
      prepared at high temperature (165  degrees C), unexpected bathochromic shift is
      successfully avoided, and a state-of-art luminous efficiency as high as 19.4 cd
      A(-1) is achieved. The efficiency is comparable to the corresponding physical
      blend system, which indicates that the fluorinated poly(arylene ether phosphine
      oxide) has the potential to be used as the platform for the development of high
      performance all-phosphorescent white polymer based on single polymer system.

PMID- 22950599
TI  - In vivo functional expression of a screened P. aeruginosa chaperone-dependent
      lipase in E. coli.
AB  - BACKGROUND: Microbial lipases particularly Pseudomonas lipases are widely used
      for biotechnological applications. It is a meaningful work to design experiments
      to obtain high-level active lipase. There is a limiting factor for functional
      overexpression of the Pseudomonas lipase that a chaperone is necessary for
      effective folding. As previously reported, several methods had been used to
      resolve the problem. In this work, the lipase (LipA) and its chaperone (LipB)
      from a screened strain named AB which belongs to Pseudomonas aeruginosa were
      overexpressed in E. coli with two dual expression plasmid systems to enhance the
      production of the active lipase LipA without in vitro refolding process. RESULTS:
      In this work, we screened a lipase-produced strain named AB through the screening
      procedure, which was identified as P. aeruginosa on the basis of 16S rDNA.
      Genomic DNA obtained from the strain was used to isolate the gene lipA (936 bp)
      and lipase specific foldase gene lipB (1023 bp). One single expression plasmid
      system E. coli BL21/pET28a-lipAB and two dual expression plasmid systems E. coli
      BL21/pETDuet-lipA-lipB and E. coli BL21/pACYCDuet-lipA-lipB were successfully
      constructed. The lipase activities of the three expression systems were compared
      to choose the optimal expression method. Under the same cultured condition, the
      activities of the lipases expressed by E. coli BL21/pET28a-lipAB and E. coli
      BL21/pETDuet-lipA-lipB were 1300 U/L and 3200 U/L, respectively, while the
      activity of the lipase expressed by E. coli BL21/pACYCDuet-lipA-lipB was up to
      8500 U/L. The lipase LipA had an optimal temperature of 30 degrees C and an
      optimal pH of 9 with a strong pH tolerance. The active LipA could catalyze the
      reaction between fatty alcohols and fatty acids to generate fatty acid alkyl
      esters, which meant that LipA was able to catalyze esterification reaction. The
      most suitable fatty acid and alcohol substrates for esterification were octylic
      acid and hexanol, respectively. CONCLUSIONS: The effect of different plasmid
      system on the active LipA expression was significantly different. pACYCDuet-lipA
      lipB was more suitable for the expression of active LipA than pET28a-lipAB and
      pETDuet-lipA-lipB. The LipA showed obvious esterification activity and thus had
      potential biocatalytic applications. The expression method reported here can give
      reference for the expression of those enzymes that require chaperones.

PMID- 22950600
TI  - Paraoxonase enzyme activity is enhanced by zinc supplementation in hemodialysis
      patients.
AB  - BACKGROUND AND AIMS: Patients on maintenance hemodialysis (HD) face an increased
      risk of atherosclerosis, a crucial problem and the leading cause of
      cardiovascular morbidity and mortality. This study was designed to evaluate the
      effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients
      on HD. METHODS: This double-blind randomized controlled trial was conducted from
      June 2005 to June 2007. Sixty HD patients were enrolled and divided into two
      groups: treatment (case) and control. The treatment and control groups were
      treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc
      concentration was measured by atomic absorption spectrophotometry. PON activity
      was evaluated by spectrophotometric method. Lipid profile was determined using
      commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were
      measured by commercial immunoturbidimetric kits. RESULTS: In the case group,
      there was no significant change in the serum total cholesterol (TC), triglyceride
      (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of
      high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly
      increased (p = 0.02). In the control group, although significant increases were
      observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001,
      respectively), the serum PON activity was significantly decreased (p = 0.025) and
      the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of
      intervention period, the serum level of Apo-AI and PON activity were
      significantly higher in the case group. CONCLUSIONS: Zinc supplementation
      increased both the activity of PON and the serum level of Apo-AI in the HD
      patients.

PMID- 22950601
TI  - Limited proteolysis via millisecond digestions in protease-modified membranes.
AB  - Sequential adsorption of poly(styrene sulfonate) (PSS) and proteases in porous
      nylon yields enzymatic membrane reactors for limited protein digestion. Although
      a high local enzyme density (~30 mg/cm(3)) and small pore diameters in the
      membrane lead to digestion in <1 s, the low membrane thickness (170 MUm) affords
      control over residence times at the millisecond level to limit digestion.
      Apomyoglobin digestion demonstrates that peptide lengths increase as the
      residence time in the membrane decreases. Moreover, electron transfer
      dissociation (ETD) tandem mass spectrometry (MS/MS) on a large myoglobin
      proteolytic peptide (8 kDa) provides a resolution of 1-2 amino acids. Under
      denaturing conditions, limited membrane digestion of bovine serum albumin (BSA)
      and subsequent ESI-Orbitrap MS analysis reveal large peptides (3-10 kDa) that
      increase the sequence coverage from 53% (2 s digestion) to 82% (0.05 s
      digestion). With this approach, we also performed membrane-based limited
      proteolysis of a large Arabidopsis GTPase, Root Hair Defective 3 (RHD3) and
      showed suitable probing for labile regions near the C-terminus to suggest what
      protein reconstruction might make RHD3 more suitable for crystallization.

PMID- 22950602
TI  - Effects of potato fiber and potato-resistant starch on biomarkers of colonic
      health in rats fed diets containing red meat.
AB  - The effects of red meat consumption with and without fermentable carbohydrates on
      indices of large bowel health in rats were examined. Sprague-Dawley rats were fed
      cellulose, potato fiber, or potato-resistant starch diets containing 12% casein
      for 2 wk, then similar diets containing 25% cooked beef for 6 wk. After week 8,
      cecal and colonic microbiota composition, fermentation end-products, colon
      structure, and colonocyte DNA damage were analyzed. Rats fed potato fiber had
      lower Bacteroides-Prevotella-Porphyromonas group compared to other diet groups.
      Colonic Bifidobacterium spp. and/or Lactobacillus spp. were higher in potato
      fiber and potato-resistant starch diets than in the cellulose diet. Beneficial
      changes were observed in short-chain fatty acid concentrations (acetic, butyric,
      and propionic acids) in rats fed potato fiber compared with rats fed cellulose.
      Phenol and p-cresol concentrations were lower in the cecum and colon of rats fed
      potato fiber. An increase in goblet cells per crypt and longer crypts were found
      in the colon of rats fed potato fiber and potato-resistant starch diets.
      Fermentable carbohydrates had no effect on colonic DNA damage. Dietary
      combinations of red meat with potato fiber or potato-resistant starch have
      distinctive effects in the large bowel. Future studies are essential to examine
      the efficacy of different types of nondigestible carbohydrates in maintaining
      colonic health during long-term consumption of high-protein diets. PRACTICAL
      APPLICATION: Improved understanding of interactions between the food consumed and
      gut microbiota provides knowledge needed to make healthier food choices for large
      bowel health. The impact of red meat on large bowel health may be ameliorated by
      consuming with fermentable dietary fiber, a colonic energy source that produces
      less harmful by-products than the microbial breakdown of colonic protein for
      energy. Developing functional red meat products with fermentable dietary fiber
      could be one way to promote a healthy and balanced macronutrient diet.

PMID- 22950603
TI  - Searching for links in the biotic characteristics and abiotic parameters of nine
      different biogas plants.
AB  - To find links between the biotic characteristics and abiotic process parameters
      in anaerobic digestion systems, the microbial communities of nine full-scale
      biogas plants in South Tyrol (Italy) and Vorarlberg (Austria) were investigated
      using molecular techniques and the physical and chemical properties were
      monitored. DNA from sludge samples was subjected to microarray hybridization with
      the ANAEROCHIP microarray and results indicated that sludge samples grouped into
      two main clusters, dominated either by Methanosarcina or by Methanosaeta, both
      aceticlastic methanogens. Hydrogenotrophic methanogens were hardly detected or if
      detected, gave low hybridization signals. Results obtained using denaturing
      gradient gel electrophoresis (DGGE) supported the findings of microarray
      hybridization. Real-time PCR targeting Methanosarcina and Methanosaeta was
      conducted to provide quantitative data on the dominating methanogens. Correlation
      analysis to determine any links between the microbial communities found by
      microarray analysis, and the physicochemical parameters investigated was
      conducted. It was shown that the sludge samples dominated by the genus
      Methanosarcina were positively correlated with higher concentrations of acetate,
      whereas sludge samples dominated by representatives of the genus Methanosaeta had
      lower acetate concentrations. No other correlations between biotic
      characteristics and abiotic parameters were found. Methanogenic communities in
      each reactor were highly stable and resilient over the whole year.

PMID- 22950604
TI  - Protective efficacy of menthol propylene glycol carbonate compared to N, N
      diethyl-methylbenzamide against mosquito bites in Northern Tanzania.
AB  - BACKGROUND: The reduction of malaria parasite transmission by preventing human
      vector contact is critical in lowering disease transmission and its outcomes.
      This underscores the need for effective and long lasting arthropod/insect
      repellents. Despite the reduction in malaria transmission and outcomes in
      Tanzania, personal protection against mosquito bites is still not well
      investigated. This study sought to determine the efficacy of menthol propylene
      glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent
      N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination
      (blend), both in the laboratory and in the field against Anopheles gambiae s.l
      and Culex quinquefasciatus. METHODS: In the laboratory evaluations, repellents
      were applied on one arm while the other arm of the same individual was treated
      with a base cream. Each arm was separately exposed in cages with unfed female
      mosquitoes. Repellents were evaluated either as a single dose or as a blend.
      Efficacy of each repellent was determined by the number of mosquitoes that landed
      and fed on treated arms as compared to the control or among them. In the field,
      evaluations were performed by human landing catches at hourly intervals from
      18:00  hr to 01:00  hr. RESULTS: A total of 2,442 mosquitoes were collected
      during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66
      (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar
      protective efficacy ranging from 92% to 100 for both single compound and blends.
      These findings indicate that MR08 has a similar protective efficacy as DEET for
      personal protection outside bed nets when used singly and in blends. Because of
      the personal protection provided by MR08, DEET and blends as topical applicants
      in laboratory and field situations, these findings suggest that, these repellents
      could be used efficiently in the community to complement existing tools. Overall,
      Cx. quinquefasciatus were significantly prevented from blood feeding compared to
      An. gambiae s.l. CONCLUSION: The incorporation of these topical repellents for
      protection against insect bites can be of additional value in the absence or
      presence of IRS and ITNs coverage. However, a combination of both the physical
      (bed nets) and the repellent should be used in an integrated manner for maximum
      protection, especially before going to bed. Additional research is needed to
      develop repellents with longer duration of protection.

PMID- 22950605
TI  - Molecular dynamics studies on the adaptability of an ionic liquid in the
      extraction of solid nanoparticles.
AB  - Recently, a number of publications have suggested that ionic liquids (ILs) can
      absorb solid particles. This development may have implications in fields like oil
      sand processing, oil spill beach cleanup, and water treatment. In this Article,
      we provide a computational investigation of this phenomenon via molecular
      dynamics simulations. Two particle surface chemistries were investigated: (1)
      hydrocarbon-saturated and (2) silanol-saturated, representing hydrophobic and
      hydrophilic particles, respectively. Employing 1-butyl-3-methylimidazolium
      hexafluorophosphate ([BMIM][PF(6)]) as a model IL, these nanoparticles were
      allowed to equilibrate at the IL/water and IL/hexane interfaces to observe the
      interfacial self-assembled structures. At the IL/water interface, the hydrocarbon
      based nanoparticles were nearly completely absorbed by the IL, while the silica
      nanoparticles maintained equal volume in both phases. At the IL/hexane interface,
      the hydrocarbon nanoparticles maintained minimal interactions with the IL,
      whereas the silica nanoparticles were nearly completely absorbed by it. Studies
      of these two types of nanoparticles immersed in the bulk IL indicate that the
      surface chemistry has a great effect on the corresponding IL liquid structure.
      These effects include layering of the ions, hydrogen bonding, and irreversible
      absorption of some ions to the silica nanoparticle surface. We quantify these
      effects with respect to each nanoparticle. The results suggest that ILs likely
      exhibit this absorption capability because they can form solvation layers with
      reduced dynamics around the nanoparticles.

PMID- 22950606
TI  - Scoring system predictive of survival for patients undergoing stereotactic body
      radiation therapy for liver tumors.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment
      option for liver tumors. This study evaluated outcomes after SBRT to identify
      prognostic variables and to develop a novel scoring system predictive of
      survival. METHODS: The medical records of 52 patients with a total of 85 liver
      lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty
      four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary
      tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT.
      The median prescribed dose was 30 Gy (range, 16 - 50 Gy) in a median of 3
      fractions (range, 1-5). RESULTS: With median follow-up of 11.3 months, median
      overall survival (OS) was 12.5 months, and 1 year OS was 50.8%. In 42 patients
      with radiographic follow up, 1 year local control was 74.8%. On univariate
      analysis, number of lesions (p = 0.0243) and active extralesional disease (p <
      0.0001) were predictive of OS; Karnofsky Performance Status (KPS) approached
      statistical significance (p = 0.0606). A scoring system for predicting survival
      was developed by allocating 1 point for each of the three following factors:
      active extralesional disease, 2 or more lesions, and KPS <= 80%. Score was
      associated with OS (p < 0.0001). For scores of 0, 1, 2 and 3, median survival
      intervals were 34, 12.5, 7.6, and 2.8 months, respectively. CONCLUSIONS: SBRT
      offers a safe and feasible treatment option for liver tumors. A prognostic
      scoring system based on the number of liver lesions, activity of extralesional
      disease, and KPS predicts survival following SBRT and can be used as a guide for
      prospective validation and ultimately for treatment decision-making.

PMID- 22950607
TI  - Backyard poultry raising in Bangladesh: a valued resource for the villagers and a
      setting for zoonotic transmission of avian influenza. A qualitative study.
AB  - INTRODUCTION: Backyard poultry raising is common in rural communities and a
      valued resource that provides food and income for subsistence farmers. Close
      contact with infected backyard poultry has been associated with H5N1 human cases
      in different countries. The emergence of this virus within Bangladesh means that
      backyard poultry raisers are at risk of avian influenza infections. The aim of
      this study was to understand why people raise backyard poultry and to
      characterize people's regular interaction with their poultry. METHODS: In 2008, a
      qualitative study was conducted in two villages from two districts of Bangladesh.
      In a social mapping exercise the villagers drew all the households in their
      village: 115 households in the village in Netrokona and 85 households in the
      village in Rajshahi District. Selected were 40 households (20 households from
      each of the two villages) for data collection through in-depth interviews (n=40)
      and household mapping (n=40), and observation sessions (n=16). RESULTS: In both
      villages, 92% of households raised backyard poultry. The majority of the owners
      was female and used the money earned from poultry raising to purchase cooking
      ingredients, clothing, and agricultural seeds, and pay for children's education
      expenses. The households consumed poultry meat and eggs. In the village in
      Netrokona, 80% (85/106) of households kept poultry inside the bedroom. In the
      village in Rajshahi, 87% (68/78) of households had separate cage/night sheds.
      During feeding the poultry and cleaning the poultry raising areas, villagers came
      into contact with poultry and poultry feces. Poultry scavenged for food on the
      floor, bed, in the food pot and around the place where food was cooked. Poultry
      drank from and bathed in the same body of water that villagers used for bathing
      and washing utensils and clothes. CONCLUSION: Although raising poultry provides
      essential support to the families' livelihoods, it exposes them to the risk of
      avian influenza through close contact with their poultry. Simple warnings to
      avoid poultry contact are unlikely to change practices that are essential to
      household survival. Interventions that help to protect poultry flocks and improve
      household profitability are more likely to be practiced.

PMID- 22950608
TI  - Cabazitaxel: a novel drug for hormone-refractory prostate cancer.
AB  - Cabazitaxel has recently been approved by FDA for the treatment of docetaxel
      resistant hormone-refractory prostate cancer. It has been developed by Sanofi
      Aventis under the trade name of Jevtana. It is given in combination with
      prednisone/prednisolone and has passed the clinical trial over well-known drug
      mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can
      penetrate blood brain barrier (BBB). The FDA granted fast track designation to
      this drug in November 2009 and thereafter, new drug application submission was
      done in March 2010. Priority review to this drug was granted in April 2010 and
      finally in July 2010 it was approved by FDA. It is available in the form of
      injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use
      by the diluents supplied along with the injection. It is a second-line drug and
      has proven to be effective in patients experiencing docetaxel based treatment
      failure.

PMID- 22950609
TI  - Frequency vs. intensity: which should be used as anchors for self-report
      instruments?
AB  - BACKGROUND: The aim of the present study was to investigate the usability of
      verbal rating scale anchors in patients suffering from a depressive episode and
      whether differences between frequency or intensity scales could be determined.
      Frequency and intensity terms were evaluated concerning their interindividual
      congruency, intraindividual stability across time, and distinguishability of
      adjacent terms. METHODS: In a longitudinal design, 44 patients (age M=39.1,
      SD=15.2, 68.2% female) with a depressive disorder filled out several established
      questionnaires (e.g. BDI or SCL-90) and questionnaires containing frequency and
      intensity terms which should be indicated by the percentage of time or intensity
      that is reflected by each term at two different measuring times within one week.
      Data analysis contained t-tests for paired samples and effect sizes d according
      to Cohen. RESULTS: Intensity terms showed weaker intraindividual stability across
      time as compared to frequency terms. Participants were able to reliably
      distinguish four frequency and intensity terms at both measuring times. Overall
      congruency between patients was larger for intensity terms in comparison to
      frequency terms. CONCLUSIONS: The present results indicate that both frequency
      and intensity terms can be applied as verbal anchors for clinical self-report
      scales. However, if longitudinal assessment is intended, our results indicate
      that frequency terms should be used as they showed slightly greater stability
      across time. Generally, the present study suggests that no more than four
      different verbal anchors should be used together in rating scales as especially
      older patients and those with low lexical experience would not be able to
      reasonably differentiate more than these.

PMID- 22950610
TI  - Women's health and the Millennium Development Goals: a long way to go.

PMID- 22950611
TI  - Short-term behavioral changes in pregnant women after a quit-smoking program via
      e-learning: a descriptive study from Japan.
AB  - Approximately 20% of Japanese women in their reproductive years are smokers.
      Therefore, in the present study, we report the behavioral changes of woman who
      undertook a 3 month stop-smoking program. Sixty-six pregnant smokers in the first
      trimester of pregnancy participated in this study from two hospitals and an
      obstetric clinic in Japan. Our newly-developed e-learning program uses a cell
      phone Internet connection service to support pregnant women who want to quit
      smoking. Using this, service participants were given guidance concerning smoking,
      and were breath tested for their carbon monoxide levels every 4 weeks for 3
      months. An e-learning cessation smoking-support program was maintained throughout
      the same period. Consequently, 52 of 66 pregnant smokers from three settings
      began the program, and 48 of 52 eventually completed it. The achievement rate of
      non-smoking was 71.1% (37/48), and their carbon monoxide exhalation levels
      significantly decreased from 6.43 +/- 4.5 ppm at the beginning to 0.7 +/- 1.0 ppm
      in 1 month, to 0.29 +/- 1.08 in 3 months (P < 0.001). These results suggest the
      effectiveness of our e-leaning program. This paper reports the results of the
      study.

PMID- 22950612
TI  - Lived experience of Thai women and their changing bodies in midlife.
AB  - This study focused on the lived experience of Thai women and their changing
      bodies in midlife. The methodology chosen was a phenomenological approach.
      Eighteen women aged 46-55 years, who lived in the southern Thailand and
      identified themselves as experiencing physiological changes, participated in the
      study. Five themes became apparent during the analysis of the women's stories:
      changing in midlife, sensing normal phenomena, searching for explanation, sense
      of loss, and self-managing. This study reveals that Thai women's traditional ties
      to Buddhism play a major role in their acceptance of midlife as part of the life
      cycle; an event that is best managed with support from other women. Health
      professionals should reconsider their understanding of women's midlife
      experiences in order to provide effective healthcare support to Thai women.

PMID- 22950613
TI  - Interpersonal psychotherapy-oriented program for Chinese pregnant women:
      delivery, content, and personal impact.
AB  - The interpersonal psychotherapy-oriented childbirth education program has the
      potential to promote social support and maternal role competence and prevent
      postpartum depression in Chinese women. The present study explored the
      perceptions of Chinese women about the delivery, content, and personal impact of
      the interpersonal psychotherapy-oriented childbirth education program. The study
      was conducted in a regional teaching hospital in China. The intervention was
      based on the principles of interpersonal psychotherapy, and consisted of two 90
      min antenatal classes and a telephone follow up within 2 weeks after delivery.
      Ninety two women, pregnant for the first time, completed the program. The Program
      Satisfaction Questionnaires, with five open-ended questions, was used for the
      process evaluation (n = 83), and a one-on-one, in-depth interview was used for
      the outcome evaluation (n = 20). The findings suggested that the program could
      facilitate the participants' adjustment to motherhood, help to establish or
      improve their relationships, and enhance their perceived social support and
      maternal role competence. Future programs could be strengthened by lengthening
      the program and adding more interactive learning.

PMID- 22950614
TI  - Health supervision of young women during pregnancy and early motherhood: a
      Norwegian qualitative study.
AB  - This study describes and interprets midwives' and public health nurses'
      perceptions of their experiences of caring for young women during pregnancy and
      early motherhood. A number of studies suggest that teenage pregnancy is
      associated with many adverse psychological, physical, social, and financial
      outcomes. Multistage focus group interviews were conducted with six
      professionals, and a qualitative content analysis was performed. The result of
      this descriptive and explorative study comprised one main theme, creating a
      trusting and committed relationship to support immature young women,
      characterized by two themes: searching for security and love in daily life and
      active involvement with "the children of their hearts". In summary, in order to
      support the young women, the informants used modeling as a strategy to achieve
      self-esteem, thus helping them to cope with daily life. Continuity of team
      supervision should be improved to enhance midwives' and public health nurses'
      professional roles.

PMID- 22950615
TI  - Performance care practices in complementary and alternative medicine by Thai
      breast cancer survivors: an ethnonursing study.
AB  - The purpose of this study was to explore how Thai breast cancer survivors perform
      care practices in complementary and alternative medicine to promote their health
      and well-being. Research was conducted using an ethnonursing method. Data were
      collected through semi-structured interviews with 17 Thai breast cancer survivors
      in Thailand. The transcribed interviews were analyzed using the ethnonursing
      analysis method. The findings showed Thai breast cancer survivors started their
      care practices in complementary and alternative medicine immediately following a
      diagnosis of breast cancer. They sought out and gathered alternative medicine
      information from several sources, such as the people around them, media
      resources, books, magazines, or newspapers. After gathering information, Thai
      breast cancer survivors would try out various types of complementary medicines
      rather than use only one type because of information from other people and their
      own evaluation. The findings of this study indicate the need for a conversation
      about complementary medicine use between healthcare providers and Thai breast
      cancer survivors as an on-going process throughout the cancer trajectory to
      ensure that safe and holistic care is provided.

PMID- 22950616
TI  - Effect of intimate partner violence on postpartum women's health in northeastern
      Thailand.
AB  - In the present study, we investigated the prevalence of psychological, physical,
      and sexual violence perpetrated by an intimate partner, and the effects on health
      status of postpartum women who gave birth at two tertiary hospitals in
      northeastern Thailand. Participants were recruited during pregnancy and
      interviewed at 6 weeks' postpartum. Measures included the Short Form 12-Item
      Health Survey, Psychological Maltreatment of Women Inventory, and Severity of
      Violence against Women scale. Participants reported high rates of psychological
      abuse, threats and/or acts of physical abuse, and sexual violence. Abused
      postpartum women had lower well-being than non-abused women on all Short Form 12
      Item Health Survey subscales, except the general health subscale. These women
      also had significant poorer health compared to non-abused women, in social
      functioning and mental health. The study findings suggest that routine screening
      for intimate partner violence by maternity services is urgently needed.

PMID- 22950617
TI  - Childbirth experience of migrants in China: a systematic review.
AB  - As preliminary research into the childbirth experience of migrants in China, this
      paper presents a systematic review of Chinese and English literature published
      between 1999 and 2011 on childbirth in migrants in China. Electronic databases
      were accessed and papers were found by keyword search. A total of 132 Chinese and
      9 English papers were catalogued for review. These papers address migrant
      maternity issues concerning antenatal, intrapartum, postnatal care, institutional
      issues, family planning or birth control. Since China's economic reforms, the
      healthcare infrastructure has been inadequate for childbirth in migrants. They
      experience more adverse birth outcomes than local residents. This suggests that
      the effects of change upon childbirth and the existing urban and rural care
      systems cannot meet the needs of the migrants. There is a lack of research in the
      childbirth experience of women. Knowledge of their childbirth experience will
      contribute to the understanding of these needs, informing systems' reform. The
      medical approach results in many unnecessary interventions and higher costs. It
      is argued here that a midwifery model of care is most appropriate for the
      childbirth experience of migrant women.

PMID- 22950618
TI  - Do Thai parents really know about the sexual risk taking of their children? A
      qualitative study in Bangkok.
AB  - This qualitative study explores the perceptions of parents and adolescents toward
      sexual risk-taking behaviors. In-depth interviews were conducted with 30 parents
      and 30 adolescents (aged 13-14 years) in Bangkok, and were analyzed by using
      coding and thematic analysis. The results showed that although parents generally
      believed that Thai teens begin to have sex at an early age and engage in sexual
      risk-taking behaviors, they trusted that their teens would follow parental
      guidance and rules and not engage in sexual activity at this age. Most of the
      Thai teens reported that their parents were not really aware of their sexual
      behaviors because of their tendency to keep their sexual stories secret for fear
      of being scolded, blamed, and punished. The teens also reported that they wanted
      their parents to listen, give them warmth and more freedom, and be more in touch
      with their activities. Parents expressed their need for knowledge and skills so
      that they could help guide their adolescent children to avoid sexual risk-taking
      behaviors. A family intervention specifically aimed at empowering Thai urban
      parents is needed.

PMID- 22950619
TI  - The life experiences of Korean children and adolescents with complex congenital
      heart disease: a qualitative study.
AB  - This exploratory study analyzed the life experiences of Korean children and
      adolescents with complex congenital heart disease in a sociocultural context and
      undertook in-depth interviews. Participants were 10 patients who ranged in age
      from 14 to 22 years, who were recruited at a hospital in Seoul, Korea. Our
      content analysis showed that the participants were initially unaware of the true
      nature of their conditions. After entering school, they realized that they were
      different from peers because of their physical limitations and their parents'
      overprotectiveness. Generally, health providers tend to convey information about
      congenital heart disease to parents, and not the patients. Therefore, most of our
      participants lacked knowledge about their disease and its management, and tended
      to have feelings of isolation and guilt. Healthcare providers of children and
      adolescents should provide disease and management information not only to
      parents, but also to patients, and should set aside specific times for
      communication with patients with complex congenital heart disease.

PMID- 22950620
TI  - Consistency analysis of parenting styles in Thailand during children's first
      year.
AB  - This descriptive study identifies and examines the consistency of parenting
      styles during the first year of their children's lives. The data were collected
      from interviewing 4088 parents or primary care takers of the 6 month old infants
      during the third wave of data collection of The Prospective Cohort of Thai
      Children project. The instrument used was the Infant Parenting Styles
      Questionnaire, developed by the researchers, which reflected parental responses
      to infant care in five different situations. After the answers were categorized
      into controlling, reasoning, overprotection, and neglectful parenting styles, the
      weighted kappa was used for the consistency analysis. The findings revealed that
      during the first 6 months of life, the overprotection style was the most common,
      followed by the reasoning style. The controlling and neglectful styles were very
      seldom used. The consistency of the parental styles in the same care givers using
      the kappa values showed that agreement between each of the styles was very low (
      0.0419 to 0.0688). This suggests that parenting styles during the first year of
      life seem to occur in random patterns.

PMID- 22950621
TI  - Advanced nursing roles: a systematic review.
AB  - In this systematic literature review, we analyzed and synthesized the literature
      on one specialized advance practice nursing role in three countries for the
      purpose of describing and comparing these roles, as well as discussing whether an
      international consensus of the advance practice nursing definition is possible. A
      systematic search on CINAHL and PubMed Medline was conducted in 2011 to search
      the literature on the nurse consultant in the UK, the clinical nurse specialist
      in the USA, and the clinical nurse consultant in Australia. The studies (n = 42)
      were analyzed and combined using qualitative content analysis method. The roles
      of the nurse consultant, clinical nurse specialist, and clinical nurse consultant
      were similar. The variation in the roles appears to derive from organizational or
      individual choices, not the country in question. The study process comprised a
      synthesized representation of one specialized advance practice nursing role. More
      work is needed to further define the concept of the advance practice nursing, as
      well as its implementation on other cultures beyond this review. Based on this
      review, an international consensus regarding the definition of advance practice
      nursing and its subroles is possible.

PMID- 22950622
TI  - Solar cell efficiency, self-assembly, and dipole-dipole interactions of
      isomorphic narrow-band-gap molecules.
AB  - We examine the correlations of the dipole moment and conformational stability to
      the self-assembly and solar cell performance within a series of isomorphic,
      solution-processable molecules. These charge-transfer chromophores are described
      by a D(1)-A-D-A-D(1) structure comprising electron-rich 2-hexylbithiophene and
      3,3'-di-2-ethylhexylsilylene-2,2'-bithiophene moieties as the donor units D(1)
      and D, respectively. The building blocks 2,1,3-benzothiadiazole (BT) and
      [1,2,5]thiadiazolo[3,4-c]pyridine (PT) were used as the electron-deficient
      acceptor units A. Using a combination of UV-visible spectroscopy, field-effect
      transistors, solar cell devices, grazing incident wide-angle X-ray scattering,
      and transmission electron microscopy, three PT-containing compounds (1-3) with
      varying regiochemistry and symmetry, together with the BT-based compound 5,5'
      bis{(4-(7-hexylthiophen-2-yl)thiophen-2-yl)-[1,2,5]thiadiazolobenzene}-3,3'-di-2
      ethylhexylsilylene-2,2'-bithiophene (4), are compared and contrasted in solution,
      in thin films, and as blends with the electron acceptor [6,6]-phenyl-C(70)
      butyric acid methyl ester. The molecules with symmetric orientations of the PT
      acceptor, 1 and 2, yield highly ordered blended thin films. The best films,
      processed with the solvent additive 1,8-diiodooctane, show donor "crystallite"
      length scales on the order of 15-35 nm and photovoltaic power conversion
      efficiencies (PCEs) of 7.0 and 5.6%, respectively. Compound 3, with an
      unsymmetrical orientation of PT heterocycles, shows subtle differences in the
      crystallization behavior and a best PCE of 3.2%. In contrast, blends of the BT
      containing donor 4 are highly disordered and give PCEs below 0.2%. We speculate
      that the differences in self-assembly arise from the strong influence of the BT
      acceptor and its orientation on the net dipole moment and geometric description
      of the chromophore.

PMID- 22950623
TI  - Short-term teriparatide treatment does not affect NT-proBNP, a marker of cardiac
      disease.
AB  - BACKGROUND: Teriparatide (Parathyroid hormone (PTH) 1-34) has been shown to
      increase bone mineral density (BMD) and reduce the risk of vertebral fractures
      when given intermittently. In contrast primary hyperparathyroidism (PHPT) is
      associated with increased bone loss. Moreover an increased occurrence of
      cardiovascular disease (CVD) is seen in PHPT patients. The N-terminal fragment of
      the pro-peptide of Brain Natriuretic peptide (NT-proBNP), a risk marker of CVD,
      has been shown to be elevated in PHPT patients, indicating that continuously high
      concentrations of PTH affect the heart. Therefore the aim of this study was to
      investigate whether teriparatide treatment is associated with changes in plasma
      NT-proBNP. METHODS: A total of 42 patients receiving teriparatide treatment were
      included in the study. Blood samples were taken at baseline, and after 1, 3 and 6
      months of treatment. Plasma concentrations of NT-proBNP were measured. Plasma
      concentrations of ionized calcium, PTH and alkaline phosphatase (ALP) were also
      analyzed, and BMD for the lumbar spine and total hip was recorded at baseline and
      after 6 months. RESULTS: Data from 10 men and 32 women, mean age 68 years, were
      included in the analysis. No effect of teriparatide on plasma concentrations of
      NT-proBNP was observed at any time points. Ionized calcium and ALP concentrations
      in the plasma increased after 6 months of treatment, whereas PTH concentrations
      decreased. Spine BMD T-score was significantly increased after 6 months of
      treatment. CONCLUSION: After 6 months of treatment with teriparatide, it did not
      change the concentration of NT-proBNP in plasma, suggesting that intermittent
      exposure to therapeutic levels of teriparatide does not affect heart function.

PMID- 22950624
TI  - The activity of paraoxonase and arylesterase in patients with osteomyelitis.
AB  - BACKGROUND: The aim of this study was to evaluate oxidative stress and to
      determine the activity of paraoxonase and arylesterase in patients with
      osteomyelitis compared to healthy controls. METHOD: In total, 30 patients
      diagnosed with osteomyelitis and 30 healthy volunteers were enrolled in the
      study. Paraoxonase and arylesterase activities were measured
      spectrophotometrically. Serum lipid hydroperoxide (LOOH) concentrations were
      measured by ferrous oxidation with xylenol orange (FOX) assay as markers of
      oxidative stress. RESULTS: Serum paraoxonase and arylesterase activities were
      significantly lower in patients with osteomyelitis compared to control
      individuals (all p < 0.05). Serum LOOH concentrations were significantly higher
      in patients with osteomyelitis than those in controls (p < 0.05). Arylesterase
      activity was inversely correlated with triglyceride (r =- 0.49; p = 0.005) and
      cholesterol concentrations (r =- 0.41; p = 0.025). CONCLUSION: In light of the
      findings obtained from the present study, it may be assumed that decreased
      activity of serum paraoxonase and increased concentrations of LOOH observed in
      osteomyelitis patients appear to be related to the increased oxidative stress and
      inflammatory conditions present in these patients, and may cause a much more
      severe status of the disease.

PMID- 22950625
TI  - Clinicopathological significance and prognostic value of MMP-13 expression in
      colorectal cancer.
AB  - The purpose of this study was to evaluate the association of matrix
      metalloproteinase-13 (MMP-13) expression with clinicopathological features and
      prognosis in colorectal cancer (CRC) patients. CRC tissues and distal normal
      mucosa tissues of 158 CRC patients were detected by immunohistochemistry. The
      correlations between MMP-13 expression, the patients' clinicopathological
      features, and overall survival rate were analyzed. It was found that positive
      expression rate of MMP-13 in distal normal mucosa tissues was significantly lower
      than that in CRC tissues (36.7% vs 60.8%, p < 0.001). Poor histological
      differentiation, advanced clinical stage and lymph node metastasis were
      significantly correlated with the MMP-13 expression in CRC. The overall survival
      rate of the MMP-13-negative group was significantly higher than the positive
      group (Log-rank test = 12.452, p < 0.001). Collectively, we found that MMP-13 was
      correlated with progression and metastasis of CRC and could be used as a
      prognostic marker in CRC.

PMID- 22950626
TI  - Plasma concentrations of asymmetric dimethylarginine, nitric oxide and
      homocysteine in patients with slow coronary flow.
AB  - OBJECTIVES: Slow coronary flow (SCF) is slow progression of contrast agent in the
      coronary arteries in the absence of stenosis in epicardial coronary vessels.
      Endothelial dysfunction and diffuse atherosclerosis have been proposed for the
      etiology of SCF. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of
      nitric oxide synthesis, levels are associated with an increased risk of
      endothelial dysfunction and atherosclerosis. ADMA levels may be increased by
      homocysteine. The aim of this study was to evaluate the relationship between
      ADMA, nitric oxide and homocysteine in patients with SCF. METHODS: The study
      group consisted of 50 patients with SCF. An age- and gender-matched control group
      was composed of 30 patients with normal coronary arteries and normal coronary
      flow on coronary angiography. We measured ADMA, nitric oxide and homocysteine
      plasma concentrations in all patients. RESULTS: Plasma nitric oxide
      concentrations were significantly lower in the SCF group than in the control
      group (11.4 +/- 6, 16.1 +/- 9, p = 0.02). Plasma ADMA concentrations (0.9 +/-
      0.3, 0.7 +/- 0.3, p = 0.01) and plasma homocysteine concentrations (12.4 +/- 5,
      9.8 +/- 2, p = 0.03) were significantly higher in the SCF group than control
      group. The mean TIMI frame count (TFC) was significantly correlated with plasma
      ADMA (r = 0.26, p = 0.02) and homocysteine (r = 0.28, p = 0.02) concentrations,
      but not with nitric oxide concentrations (r = - 0.18, p = 0.13). In linear
      regression analysis, plasma ADMA concentrations (beta = 4.6, p = 0.005) and
      homocysteine concentrations (beta = 0.2, p = 0.03) were independently and
      positively associated with mean TFC. CONCLUSION: Our results suggest that plasma
      concentrations of ADMA and homocysteine are increased in SCF and also that these
      are independent predictors of SCF.

PMID- 22950627
TI  - A novel appetite peptide, nesfatin-1 in patients with non-alcoholic fatty liver
      disease.
AB  - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the most
      common liver pathology worldwide and is strongly associated with obesity and
      insulin-resistance and food intake. Nesfatin-1 is a new peptide that controls
      appetite and food intake. The objective of this research was to examine the serum
      concentrations of nesfatin-1 in NAFLD. MATERIAL AND METHODS: Thirty NAFLD
      patients who had elevated liver enzymes and 40 age- and sex-matched healthy
      subjects were included in this study. NAFLD was diagnosed and graded with the
      findings of liver ultrasound scan. Nesfatin-1 concentrations were measured using
      an ELISA method and the relationship between nesfatin-1 and metabolic parameters
      were investigated. The subjects were divided into two groups according to their
      body mass index (>= 30 and < 30) and nesfatin-1 concentrations were examined
      between both groups. RESULTS: Serum nesfatin-1 concentrations in NAFLD patients
      were lower than healthy controls (0.26 +/- 0.14 ng/ml, 0.38 +/- 0.18 ng/ml,
      respectively, and p = 0.008). We found a negative correlation between nesfatin-1
      and fasting glucose and body mass index. In obese subjects, serum nesfatin-1
      concentrations were significantly lower when compared with non-obese subjects
      (0.26 +/- 0.12 ng/ml, 0.37 +/- 0.19 ng/ml, respectively; p = 0.014). In addition,
      we showed that nesfatin-1 concentrations in subjects with insulin resistance were
      significantly lower in comparison with insulin-sensitive ones (0.27 +/- 0.17
      ng/ml, 0.38 +/- 0.17 ng/ml, respectively; p = 0.015). CONCLUSION: Our study has
      shown that nesfatin-1 concentrations were reduced in NAFLD. The results of this
      study indicate that nesfatin-1 may have a significant role in NAFLD.

PMID- 22950629
TI  - Factors associated with above and under 5-year survival in peritoneal dialysis
      patients.
AB  - BACKGROUND/AIMS: A few patients stay on peritoneal dialysis (PD) for 5 years or
      longer from initiation of therapy. We investigated patient survival and factors
      affecting mortality in PD patients. METHODS: This was a retrospective study
      including 354 PD patients. The demographic, clinical, and biochemical data were
      collected from the medical records. Two hundred patients were excluded.
      Evaluation was carried out on data from 154 patients, including 83 surviving 5
      years or more and 71 who were taken as surviving less than 5 years. RESULTS: Mean
      age, number of comorbid diseases, prevalence of diabetes mellitus (DM), rate of
      mandatory preference of PD, making their PD exchanges with help from anyone were
      lower in surviving patients, and education level was higher in surviving
      patients. Advanced age, high rate of mandatory preference of PD, high rate of
      baseline high, and high-average peritoneal transporters were associated with an
      increased risk of death. CONCLUSION: Long-term survival is possible for PD
      patients, particularly nondiabetics, those having higher education level, those
      with a self-preference of PD, and those making PD exchanges without any help.

PMID- 22950628
TI  - High molecular mass proteomics analyses of left ventricle from rats subjected to
      differential swimming training.
AB  - BACKGROUND: Regular exercises are commonly described as an important factor in
      health improvement, being directly related to contractile force development in
      cardiac cells.In order to evaluate the links between swimming exercise intensity
      and cardiac adaptation by using high molecular mass proteomics, isogenic Wistar
      rats were divided into four groups: one control (CG) and three training groups
      (TG's), with low, moderate and high intensity of exercises.In order to evaluate
      the links between swimming exercise intensity and cardiac adaptation by using
      high molecular mass proteomics, isogenic Wistar rats were divided into four
      groups: one control (CG) and three training groups (TG's), with low, moderate and
      high intensity of exercises. RESULTS: Findings here reported demonstrated clear
      morphologic alterations, significant cellular injury and increased energy
      supplies at high exercise intensities. alpha-MyHC, as well proteins associated
      with mitochondrial oxidative metabolism were shown to be improved. alpha-MyHC
      expression increase 1.2 fold in high intensity training group when compared with
      control group. alpha-MyHC was also evaluated by real-time PCR showing a clear
      expression correlation with protein synthesis data increase in 8.48 fold in high
      intensity training group. Other myofibrillar protein, troponin , appear only in
      high intensity group, corroborating the cellular injury data. High molecular
      masses proteins such as MRS2 and NADH dehydrogenase, involved in metabolic
      pathways also demonstrate increase expression, respectily 1.5 and 1.3 fold, in
      response to high intensity exercise. CONCLUSIONS: High intensity exercise
      demonstrated an increase expression in some high molecular masses myofibrilar
      proteins, alpha-MyHC and troponin. Furthermore this intensity also lead a
      significant increase of other high molecular masses proteins such as MRS2 and
      NADH dehydrogenase in comparison to low and moderate intensities. However, high
      intensity exercise also represented a significant degree of cellular injury, when
      compared with the individuals submitted to low and moderate intensities.

PMID- 22950630
TI  - Prevalence of Toxoplasma gondii antibodies, circulating antigens and DNA in stray
      cats in Shanghai, China.
AB  - BACKGROUND: Toxoplasma gondii is prevalent in most areas of the world and may
      cause abortions or neonatal complications in humans. As the only definitive host,
      cats play an important role in the epidemiology of the disease. Infection rates
      in cats, especially stray or free-living cats, are considered to be the best
      sentinels of the level of T. gondii in the environment. The T. gondii infection
      can be diagnosed in different ways with different methods depending on the
      target. However, little information on T. gondii infection in cats was available
      in Shanghai, China. Moreover reports on prevalence of circulating antigens,
      antibodies and DNA of T. gondii in the same study are rare. METHODS: In the
      present study, the presence of antibodies (Ab), circulating antigens (CA), and/or
      DNA of Toxoplasma gondii in samples from 145 stray or unwanted cats from 6 animal
      shelters in Shanghai (China) was determined in order to estimate the prevalence
      of T. gondii infection, by Ab-ELISA, CA-ELISA, and nested-PCR, respectively.
      RESULTS: The positive rates for the antibodies, circulating antigen and DNA of T.
      gondii were 11.7% (17 of 145), 5.5% (8 of 145) and 5.71% (2 of 35), respectively.
      No cat tested was positive by both the Ab-ELISA and the CA-ELISA, but the results
      of the PCR were consistent with the CA-ELISA assay. Therefore, the overall
      estimated prevalence of toxoplasmosis was 17.2% (25 of 145). According to our
      results, the positive rates of specific antibodies and circulating antigen of T.
      gondii were significantly different between adult cats (>1 year old) and juvenile
      cats (<=1 year old); the former was 13.5% versus 3.9% by Ab-ELISA, while the
      latter was 1.7% versus 23.1% by CA-ELISA. From the results obtained with all
      three detection methods used in this study, the rate of infection was not
      significantly different between male and female cats (P >=0.05); and the overall
      rate was 17.9% for males versus 16.4% for females. CONCLUSIONS: The results
      suggest that detection of circulating antigens (CA) is necessary in surveys of T.
      gondii infection, especially for juvenile cats. Our investigation revealed that
      the prevalence of T. gondii infection in stray cats in Shanghai is high. Control
      programs are needed for stray cat populations in order to reduce the risk of
      zoonotic transmission of toxoplasmosis to other domestic animals and humans,
      especially females.

PMID- 22950631
TI  - Enzyme-free and label-free ultrasensitive electrochemical detection of human
      immunodeficiency virus DNA in biological samples based on long-range self
      assembled DNA nanostructures.
AB  - Biosensors based on nanomaterials have been used for detection of various
      biological molecules with high sensitivity and selectivity. Herein, we developed
      a simple and ultrasensitive electrochemical DNA biosensor using long-range self
      assembled DNA nanostructures as carriers for signal amplification, which can
      achieve an impressive detection limit of 5 aM human immunodeficiency virus (HIV)
      DNA even in complex biological samples. In this study, we designed two auxiliary
      probes. A cascade of hybridization events between the two auxiliary probes can
      lead to long-range self-assembly and form micrometer-long one-dimensional DNA
      nanostructures. In the presence of target DNA, each copy of the target can act as
      a trigger to connect a DNA nanostructure to a capture probe on the electrode
      surface. Then, a great amount of redox indicator [Ru(NH(3))(6)](3+) can be
      electrostatically bound to the DNA nanostructures and eventually result in
      significantly amplified electrochemical signals.

PMID- 22950632
TI  - The rare disease challenge and how to promote a productive rare disease
      community: case study of Birt-Hogg-Dube symposia.
AB  - Resources for rare diseases are lacking. Patients do not have the information and
      support that they need, and researchers struggle to make progress due to a
      shortage of skills and collaborations within the field. One way to overcome these
      hurdles is to host annual Symposia, focused on a specific rare disease. Here, we
      use the example of Birt-Hogg-Dube Symposia to discuss the practical issues of
      such meetings, including the importance of timing and the choice of invited
      speakers. We highlight the ways in which rare disease symposia can create a
      single community, removing barriers between patients, clinicians and researchers.

PMID- 22950633
TI  - Oxidative stress markers in follicular fluid of women undergoing in vitro
      fertilization and embryo transfer.
AB  - The aim of the study was to evaluate the levels of lipid and protein peroxidation
      markers, in the follicular fluids (FF) of 82 patients undergoing in vitro
      fertilization (IVF). This included, thiobarbituric acid-reactive substances
      (TBARS), protein carbonyl, and thiol groups. The oxidative stress markers were
      compared between the pregnancy positive and pregnancy negative patient groups.
      The two patient groups were compared in terms of their age, body mass index
      (BMI), cause of infertility, and the plasma hormone levels (AMH, E(2), peak
      E(2)). Protein carbonyl and thiol groups were estimated using an ELISA assay and
      with Ellman's reagent (5, 5'-dithiobis-2-nitrobenzoic acid, DTNB), respectively.
      The mean FF TBARS level of 29 pregnant women was 0.954 +/- 0.420 umol/l, whereas
      it was twice as high (1.961 +/- 0.796 umol/l) in a group of 53 non-pregnant
      patients (p < 0.0001). In non-pregnant patients, we observed 2-fold elevated
      levels of protein carbonyl groups when compared to pregnant women (2.969 +/-
      0.723 vs. 1.523 +/- 0.254; p < 0.0001). The mean age of women and BMI were
      significantly higher in the pregnancy negative vs. pregnancy positive group.
      There were no significant differences in protein thiols and in the levels of the
      hormones tested between patient groups. Our results demonstrate that elevated FF
      lipid and protein peroxidation level may have a negative impact on IVF outcome.
      The findings support the idea that increased level of oxidative stress markers in
      follicular fluid may play an important role in fertility.

PMID- 22950634
TI  - Wavelet-based detection of transcriptional activity on a novel Staphylococcus
      aureus tiling microarray.
AB  - BACKGROUND: High-density oligonucleotide microarray is an appropriate technology
      for genomic analysis, and is particulary useful in the generation of
      transcriptional maps, ChIP-on-chip studies and re-sequencing of the
      genome.Transcriptome analysis of tiling microarray data facilitates the discovery
      of novel transcripts and the assessment of differential expression in diverse
      experimental conditions. Although new technologies such as next-generation
      sequencing have appeared, microarrays might still be useful for the study of
      small genomes or for the analysis of genomic regions with custom microarrays due
      to their lower price and good accuracy in expression quantification. RESULTS:
      Here, we propose a novel wavelet-based method, named ZCL (zero-crossing lines),
      for the combined denoising and segmentation of tiling signals. The denoising is
      performed with the classical SUREshrink method and the detection of
      transcriptionally active regions is based on the computation of the Continuous
      Wavelet Transform (CWT). In particular, the detection of the transitions is
      implemented as the thresholding of the zero-crossing lines. The algorithm
      described has been applied to the public Saccharomyces cerevisiae dataset and it
      has been compared with two well-known algorithms: pseudo-median sliding window
      (PMSW) and the structural change model (SCM). As a proof-of-principle, we applied
      the ZCL algorithm to the analysis of the custom tiling microarray hybridization
      results of a S. aureus mutant deficient in the sigma B transcription factor. The
      challenge was to identify those transcripts whose expression decreases in the
      absence of sigma B. CONCLUSIONS: The proposed method archives the best
      performance in terms of positive predictive value (PPV) while its sensitivity is
      similar to the other algorithms used for the comparison. The computation time
      needed to process the transcriptional signals is low as compared with model-based
      methods and in the same range to those based on the use of filters. Automatic
      parameter selection has been incorporated and moreover, it can be easily adapted
      to a parallel implementation. We can conclude that the proposed method is well
      suited for the analysis of tiling signals, in which transcriptional activity is
      often hidden in the noise. Finally, the quantification and differential
      expression analysis of S. aureus dataset have demonstrated the valuable utility
      of this novel device to the biological analysis of the S. aureus transcriptome.

PMID- 22950635
TI  - Gene expression profiling of the synergy of 5-aza-2'-deoxycytidine and paclitaxel
      against renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is one of the most common kidney cancers
      and is highly resistant to chemotherapy. We previously demonstrated that 5-aza-2'
      deoxycytidine (DAC) could significantly increase the susceptibility of renal cell
      carcinoma (RCC) cells to paclitaxel (PTX) treatment in vitro, and showed the
      synergy of DAC and PTX against RCC. The purpose of this study is to investigated
      the gene transcriptional alteration and investigate possible molecular mechanism
      and pathways implicated in the synergy of DAC and PTX against RCC. METHODS: cDNA
      microarray was performed and coupled with real-time PCR to identify critical
      genes in the synergistic mechanism of both agents against RCC cells. Various
      patterns of gene expression were observed by cluster analysis. IPA software was
      used to analyze possible biological pathways and to explore the inter
      relationships between interesting network genes. RESULTS: We found that lymphoid
      enhancer-binding factor 1 (LEF1), transforming growth factor beta-induced
      (TGFBI), C-X-C motif ligand 5 (CXCL5) and myelocytomatosis viral related oncogene
      (c-myc) may play a pivotal role in the synergy of DAC and PTX. The PI3K/Akt
      pathway and other pathways associated with cyclins, DNA replication and cell
      cycle/mitotic regulation were also associated with the synergy of DAC and PTX
      against RCC. CONCLUSION: The activation of PI3K/Akt-LEF1/beta-catenin pathway
      could be suppressed synergistically by two agents and that PI3K/Akt-LEF1/beta
      catenin pathway is participated in the synergy of two agents.

PMID- 22950636
TI  - Effect of steam baking on acrylamide formation and browning kinetics of cookies.
AB  - Effects of baking method and temperature on surface browning and acrylamide
      concentration of cookies were investigated. Cookies were baked in natural and
      forced convection and steam-assisted hybrid ovens at 165, 180, and 195  degrees C
      and at different times. For all oven types, the acrlyamide concentration and
      surface color of cookies increased with increasing baking temperature.
      Significant correlation was observed between acrylamide formation and browning
      index, BI, which was calculated from Hunter L, a, and b color values, and it
      showed that the BI may be considered as a reliable indicator of acrylamide
      concentration in cookies. Acrylamide formation and browning index in cookies were
      considered as the first-order reaction kinetics and the reaction rate constants,
      k, were in the range of 0.023 to 0.077 (min(-1) ) and 0.019 to 0.063 (min(-1) ),
      respectively. The effect of baking temperature on surface color and acrylamide
      concentration followed the Arrhenius type of equation, with activation energies
      for acrylamide concentration as 6.87 to 27.84 kJ/mol; for BI value as 19.54 to
      35.36 kJ/mol, for all oven types. Steam-assisted baking resulted in lower
      acrylamide concentration at 165  degrees C baking temperature and lower surface
      color for all temperatures. Steam-assisted baking is recommended as a healthy way
      of cooking providing the reduction of harmful compounds such as acrylamide for
      bakery goods, at a minimal level, while keeping the physical quality. PRACTICAL
      APPLICATION: The kinetics of acrylamide formation and browning of cookies will
      possibly allow definition of optimum baking temperatures and times at
      convectional and steam-assisted baking ovens. The kinetic model can be used by
      developing baking programs that can automatically control especially a new home
      scale steam-assisted hybrid oven producing healthy products, for the use of
      domestic consumers.

PMID- 22950637
TI  - Management of raised glucose, a clinical decision tool to reduce length of stay
      of patients with hyperglycaemia.
AB  - OBJECTIVE: To assess whether the introduction of a management of raised glucose
      clinical decision tool could improve assessment of patients with hyperglycaemia
      by non-specialist physicians, leading to early discharge and improved quality of
      inpatient care. METHODS: Participants were adults aged 18 years or over
      presenting to the Medical Assessment Unit with a capillary blood glucose level >
      11.1 mmol/l. Phase 1 of the study (phase 1) evaluated current clinical practice
      and potential impact of the clinical decision tool. Phase 2 evaluated the
      effectiveness of the management of raised glucose tool in clinical practice.
      Primary outcome measures were inpatient length of stay and same-calendar-day
      discharges. Secondary outcome measures were diabetes specialist input, patient
      assessment, intravenous insulin infusion use and patient satisfaction. RESULTS:
      Implementation of the management of raised glucose clinical decision tool allowed
      safe, same-calendar-day discharges of 40% of patients with hyperglycaemia as
      their primary reason for attendance. Median length of stay was lower in the phase
      1 than in phase 2 (1.0 vs. 3.5 days, P < 0.01). Early discharge did not result in
      an increase in readmissions. There was improvement in hyperglycaemia assessment
      for all patients (P < 0.01), a reduction in the use of intravenous insulin
      infusions (P < 0.01) and high level of patient satisfaction. CONCLUSION: The
      management of raised glucose clinical decision tool resulted in a significant
      increase in the number of same-calendar-day discharges and reduction in hospital
      length of stay without adverse impact on readmission rates. Additionally, the
      tool was associated with improvements in inpatient diabetes care and patient
      satisfaction.

PMID- 22950638
TI  - Ultrahigh sensitivity of Au/1D alpha-Fe2O3 to acetone and the sensing mechanism.
AB  - Hematite (alpha-Fe(2)O(3)) is a nontoxic, stable, versatile material that is
      widely used in catalysis and sensors. Its functionality in sensing organic
      molecules such as acetone is of great interest because it can result in potential
      medical applications. In this report, microwave irradiation is applied in the
      preparation of one-dimensional (1D) alpha-FeOOH, thereby simplifying our previous
      hydrothermal method and reducing the reaction time to just a few minutes. Upon
      calcination, the sample was converted to porous alpha-Fe(2)O(3) nanorods, which
      were then decorated homogeneously by fine Au particles, yielding Au/1D alpha
      Fe(2)O(3) at nominally 3 wt % Au. After calcination, the sample was tested as a
      potential sensor for acetone in the parts per million range and compared to a
      similarly loaded Pt sample and the pure 1D alpha-Fe(2)O(3) support. Gold addition
      results in a much enhanced response whereas Pt confers little or no improvement.
      From tests on acetone in the 1-100 ppm range in humid air, Au/1D alpha-Fe(2)O(3)
      has a fast response, short recovery time, and an almost linear response to the
      acetone concentration. The optimum working temperature was found to be 270 
      degrees C, which was judged to be a compromise between the thermal activation of
      lattice oxygen in hematite and the propensity for acetone adsorption. The surface
      reaction was investigated by diffuse reflectance infrared Fourier transform
      spectroscopy (DRIFTS), and a possible sensing mechanism is proposed. The presence
      of Au nanoparticles is believed to promote the dissociation of molecular oxygen
      better in replenishing O vacancies, thereby increasing the instantaneous supply
      of lattice oxygen to the oxidation of acetone (to H(2)O and CO(2)), which
      proceeds through an adsorbed acetate intermediate. This work contributes to the
      development of next-generation sensors, which offer ultrahigh detection
      capabilities for organic molecules.

PMID- 22950639
TI  - Contact sensitivity in Behcet's disease.
AB  - CONTEXT: Behcet's disease (BD) is a multisystemic inflammatory disorder with
      unknown etiology. Many immunological changes were reported in BD previously and
      these changes may affect the frequency of contact sensitivity in these patients.
      OBJECTIVE: We aimed to identify whether there is an interaction between contact
      sensitivity and BD. METHODS: The 'European standard series' with 27 allergens
      were performed on the upper backs of patients and healthy volunteers according to
      international standards using the IQ-Chamber. The test-units which contain these
      allergens were removed after 2 days. According to International Contact
      Dermatitis Research Group Recommendations test areas were evaluated on days 2, 3
      and 7 to detect any delayed allergic reactions. The results of both groups were
      compared by using chi-square test. RESULTS: One hundred adult persons (50 BDs and
      50 healthy controls) were tested. Positive patch test reaction to 1 or more
      allergens was observed in 7 (14%) patients in BD group and in 12 (24%) persons in
      control group. There was no statistically significant difference between these
      two groups. CONCLUSIONS: The frequency of contact sensitivity in BD is not
      different from healthy persons.

PMID- 22950640
TI  - Childhood caries in the state of Kentucky, USA: a cross-sectional study.
AB  - BACKGROUND: Untreated dental caries afflicts almost one third of school-aged
      children in the United States and many of them are from disadvantaged families.
      This cross-sectional study was undertaken to investigate the prevalence of
      untreated caries in north central Kentucky, USA and to examine the relationships
      between the available demographic variables and untreated childhood caries as
      reported on the forms from the Smile Kentucky! program. METHODS: During the fall
      of 2008, caries status was assessed during the visual oral screening examination
      component of "SmileKentucky!"- a model of the American Dental Association's Give
      Kids A Smile program. Parents had completed brief surveys concerning 3,488
      elementary school children aged 5 to 13 years who participated in the program. A
      secondary analysis was conducted using univariate, bivariate and multivariate
      statistical methods. RESULTS: Untreated caries was reported in 33% of children.
      Bivariate and logistic regression analyses found that the most significant risk
      factors for having untreated caries were living in the metropolitan Louisville,
      Kentucky area, not having had a dental visit in the previous 3 years and not
      having any form of dental insurance. CONCLUSIONS: Untreated caries in elementary
      school children is prevalent in north-central Kentucky despite efforts to improve
      access to care. The results suggest that additional family and community
      preventive initiatives are needed to reduce the development of childhood caries
      in this area of the United States.

PMID- 22950641
TI  - The effects of vitamin E-coated membrane dialyzer compared to simvastatin in
      patients on chronic hemodialysis.
AB  - BACKGROUND: We investigated the effects of the use of vitamin E-coated membrane
      (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation,
      oxidative stress, and endothelial cell apoptosis in ten patients on chronic
      hemodialysis (HD), aiming at distinguishing the different treatment effects and
      their time sequence on these pathogenetic routes. METHODS: Ten HD patients were
      sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of
      simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3,
      and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo)
      A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6),
      monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion
      molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1),
      soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL),
      and plasma oxidized low-density lipoproteins (oxLDL) levels were determined.
      RESULTS: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1
      at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in
      a significant decrease in CRP, which correlated with decreases in both total (r =
      0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1,
      oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1
      (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean
      difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly
      from the corresponding VEM effects. CONCLUSIONS: The 6-month use of VEM resulted
      in more direct and immediate anti-inflammatory effects compared with those caused
      by the 6-month treatment with simvastatin. Simvastatin caused a more intense
      decrease in the markers of inflammation, which was in part correlated with its
      lipid-lowering effects.

PMID- 22950643
TI  - A new insight into estrogen signaling: Yin-Yang perspective.
AB  - During recent years, new advances in the field of estrogen signaling (e.g., the
      discovery of the second estrogen receptor named ERbeta) have led to the
      conclusion that all the major human tissues are estrogen-responsive. The impact
      of estrogen on human health is far more complex and stronger than scientists had
      previously thought. Several scientists suggested that the interplay between
      ERalpha and ERbeta (antagonism, synergism, etc.) simulates a Yin-Yang
      relationship. This article is intended to integrate the Yin-Yang theory of
      Traditional Chinese Medicine with modern scientific findings on estrogen
      signaling to offer a better understanding of the complex interactions between
      ERalpha and ERbeta. A different approach, such as that of Yin-Yang theory, may
      complete the standard scientific perspective, reveal hidden meanings of the
      tissue-dependent ERalpha-ERbeta predominance, and reveal new aspects of estrogen
      receptor imbalance.

PMID- 22950642
TI  - Babesia spp. and Anaplasma phagocytophilum in questing ticks, ticks parasitizing
      rodents and the parasitized rodents--analyzing the host-pathogen-vector interface
      in a metropolitan area.
AB  - BACKGROUND: The aims of this study were to evaluate the host-tick-pathogen
      interface of Babesia spp. and Anaplasma phagocytophilum in restored areas in both
      questing and host-attached Ixodes ricinus and Dermacentor reticulatus and their
      small mammalian hosts. METHODS: Questing ticks were collected from 5 sites within
      the city of Leipzig, Germany, in 2009. Small mammals were trapped at 3 of the 5
      sites during 2010 and 2011. DNA extracts of questing and host-attached I. ricinus
      and D. reticulatus and of several tissue types of small mammals (the majority
      bank voles and yellow-necked mice), were investigated by PCR followed by
      sequencing for the occurrence of DNA of Babesia spp. and by real-time PCR for A.
      phagocytophilum. A selected number of samples positive for A. phagocytophilum
      were further investigated for variants of the partial 16S rRNA gene. Co-infection
      with Rickettsia spp. in the questing ticks was additionally investigated.
      RESULTS: 4.1% of questing I. ricinus ticks, but no D. reticulatus, were positive
      for Babesia sp. and 8.7% of I. ricinus for A. phagocytophilum. Sequencing
      revealed B. microti, B. capreoli and Babesia spp. EU1 in Leipzig and sequence
      analysis of the partial 16S RNA gene of A. phagocytophilum revealed variants
      either rarely reported in human cases or associated with cervid hosts. The
      statistical analysis revealed significantly less ticks infected with A.
      phagocytophilum in a city park in Leipzig as compared to the other sampling
      sites. A. phagocytophilum-DNA was detected in 2 bank voles, DNA of B. microti in
      1 striped field-mouse and of Babesia sp. EU1 in the skin tissue of a mole. Co
      infections were detected. CONCLUSION: Our results show the involvement of small
      mammals in the natural endemic cycles of tick-borne pathogens. A more thorough
      understanding of the interactions of ticks, pathogens and hosts is the essential
      basis for effective preventive control measures.

PMID- 22950644
TI  - An overview of viral oncology in Italy - report from the Pavia meeting on solid
      tumors.
AB  - This is a report on some of the research activities currently ongoing in Italy
      as outlined at the "Viruses and solid tumors" meeting jointly organized by the
      Oncology Sections of IRCCS Policlinico "San Matteo" (Pavia) and IRCCS National
      Cancer Institute (Aviano), held in Pavia, Italy, on October 2011. Experts from
      the various disciplines involved in the study of the complex relationships
      between solid tumors and viruses met to discuss recent developments in the field
      and to report their personal contributions to the specified topics. Secondary end
      point was to establish a multidisciplinary work group specifically devoted to
      solid tumors and infectious agents, aimed to identify areas of common interest,
      promoting and establishing collaborative projects and programs, and to coordinate
      clinical and research activities. The group, which will be named IVOG (Italian
      Viral Oncology Group), will operate under the patronage of the various scientific
      societies of interest.

PMID- 22950645
TI  - Steroidogenic and maturation-inducing potency of native gonadotropic hormones in
      female chub mackerel, Scomber japonicus.
AB  - BACKGROUND: The gonadotropins (GtHs), follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH) are produced in the pituitary gland and regulates
      gametogenesis through production of gonadal steroids. However, respective roles
      of two GtHs in the teleosts are still incompletely characterized due to technical
      difficulties in the purification of native GtHs. METHODS: Native FSH and LH were
      purified from the pituitaries of adult chub mackerel, Scomber japonicus by anion
      exchange chromatography and immunoblotting using specific antisera. The
      steroidogenic potency of the intact chub mackerel FSH (cmFSH) and LH (cmLH) were
      evaluated in mid- and late-vitellogenic stage follicles by measuring the level of
      gonadal steroids, estradiol-17beta (Epsilon2) and 17,20beta-dihydroxy-4-pregnen-3
      one (17,20beta-P). In addition, we evaluated the maturation-inducing potency of
      the GtHs on same stage follicles. RESULTS: Both cmFSH and cmLH significantly
      stimulated E2 production in mid-vitellogenic stage follicles. In contrast, only
      LH significantly stimulated the production of 17,20beta-P in late-vitellogenic
      stage follicles. Similarly, cmLH induced final oocyte maturation (FOM) in late
      vitellogenic stage follicles. CONCLUSIONS: Present results indicate that both FSH
      and LH may regulate vitellogenic processes, whereas only LH initiates FOM in chub
      mackerel.

PMID- 22950646
TI  - Single-stranded DNA curtains for real-time single-molecule visualization of
      protein-nucleic acid interactions.
AB  - Single-molecule imaging of biological macromolecules has dramatically impacted
      our understanding of many types of biochemical reactions. To facilitate these
      studies, we have established new strategies for anchoring and organizing DNA
      molecules on the surfaces of microfluidic sample chambers that are otherwise
      coated with fluid lipid bilayers. This previous work was reliant upon the use of
      double-stranded DNA, precluding access to information on biological processes
      involving single-stranded nucleic acid substrates. Here, we present procedures
      for aligning and visualizing single-stranded DNA molecules along the leading
      edges of nanofabricated barriers to lipid diffusion, in both "single-tethered"
      and "double-tethered" experimental formats. This new single-molecule approach
      provides long-awaited access to critical biological reactions involving single
      stranded DNA binding proteins.

PMID- 22950647
TI  - Segmental dataset and whole body expression data do not support the hypothesis
      that non-random movement is an intrinsic property of Drosophila retrogenes.
AB  - BACKGROUND: Several studies in Drosophila have shown excessive movement of
      retrogenes from the X chromosome to autosomes, and that these genes are
      frequently expressed in the testis. This phenomenon has led to several hypotheses
      invoking natural selection as the process driving male-biased genes to the
      autosomes. Metta and Schlotterer (BMC Evol Biol 2010, 10:114) analyzed a set of
      retrogenes where the parental gene has been subsequently lost. They assumed that
      this class of retrogenes replaced the ancestral functions of the parental gene,
      and reported that these retrogenes, although mostly originating from movement out
      of the X chromosome, showed female-biased or unbiased expression. These
      observations led the authors to suggest that selective forces (such as meiotic
      sex chromosome inactivation and sexual antagonism) were not responsible for the
      observed pattern of retrogene movement out of the X chromosome. RESULTS: We
      reanalyzed the dataset published by Metta and Schlotterer and found several
      issues that led us to a different conclusion. In particular, Metta and
      Schlotterer used a dataset combined with expression data in which significant sex
      biased expression is not detectable. First, the authors used a segmental dataset
      where the genes selected for analysis were less testis-biased in expression than
      those that were excluded from the study. Second, sex-biased expression was
      defined by comparing male and female whole-body data and not the expression of
      these genes in gonadal tissues. This approach significantly reduces the
      probability of detecting sex-biased expressed genes, which explains why the vast
      majority of the genes analyzed (parental and retrogenes) were equally expressed
      in both males and females. Third, the female-biased expression observed by Metta
      and Schlotterer is mostly found for parental genes located on the X chromosome,
      which is known to be enriched with genes with female-biased expression. Fourth,
      using additional gonad expression data, we found that autosomal genes analyzed by
      Metta and Schlotterer are less up regulated in ovaries and have higher chance to
      be expressed in meiotic cells of spermatogenesis when compared to X-linked genes.
      CONCLUSIONS: The criteria used to select retrogenes and the sex-biased expression
      data based on whole adult flies generated a segmental dataset of female-biased
      and unbiased expressed genes that was unable to detect the higher propensity of
      autosomal retrogenes to be expressed in males. Thus, there is no support for the
      authors' view that the movement of new retrogenes, which originated from X-linked
      parental genes, was not driven by selection. Therefore, selection-based genetic
      models remain the most parsimonious explanations for the observed chromosomal
      distribution of retrogenes.

PMID- 22950648
TI  - Ionome of soybean seed affected by previous cropping with mycorrhizal plant and
      manure application.
AB  - Two field experiments were conducted to investigate the effects of previous
      cultivation of an arbuscular mycorrhizal (AM) host plant and manure application
      on the concentration of 19 mineral elements in soybean ( Glycine max  L. Merr.
      cv. Tsurumusume) seeds. Each experiment ran for two years (experiment 1 took
      place in 2007-2008, and experiment 2 took place in 2008-2009) with a split plot
      design. Soybeans were cultivated after growing either an AM host plant (maize, 
      Zea mays  L. cv. New dental) or a non-AM host plant (buckwheat,  Fagopyrum
      esculentum  Moench. cv. Kitawase-soba) in the first year in the main plots, with
      manure application (0 and 20 t/ha) during the soybean season in split plots from
      both main plots. On the basis of the two experiments, manure application
      significantly increased the available potassium (K) and decreased the available
      iron (Fe) and cesium (Cs) in the soil. However, higher concentrations of cadmium
      (Cd) and barium (Ba) and lower concentrations of Cs in the seed were induced by
      the application of manure. Cd levels in the seed were decreased by prior
      cultivation with the AM host plant. The present study showed that the identity of
      the prior crop and manure application changed the mineral contents of the soybean
      seed and suggests a connection between environmental factors and food safety.

PMID- 22950649
TI  - Application of selected ion flow tube mass spectrometry coupled with chemometrics
      to study the effect of location and botanical origin on volatile profile of
      unifloral American honeys.
AB  - Ten Ohio and Indiana honey samples from star thistle (Centaurea Americana),
      blueberry (Vaccinium spp.), clover (Trifolium spp.), cranberry (Vaccinium spp.),
      wildflower, and an unknown source were collected. The headspace of these honeys
      was analyzed by selected ion flow tube mass spectrometry and soft independent
      modeling of class analogy (SIMCA). SIMCA was utilized to statistically
      differentiate between honeys based on their composition. Ohio honeys from star
      thistle, blueberry, and clover were similar to each other in volatile
      composition, while Ohio wildflower honey was different. Indiana honeys from star
      thistle, blueberry, and wildflower were different from each other in volatile
      composition, while clover and cranberry honeys were similar. Honeys from Ohio and
      Indiana with the same floral origins were different in volatile composition.
      Furfural, 1-octen-3-ol, butanoic, and pentanoic acids were the volatiles with the
      highest discriminating power between types of floral honey. Methanol and ethanol
      followed by acetic acid were at the highest levels in most honeys, though
      furfural was at the highest concentration in Indiana blueberry honey, while 1
      octen-3-ol was at the highest concentration in Indiana wildflower honey. The
      highest concentration of volatile compounds was in Indiana wildflower honey
      followed by Ohio wildflower honey, while the lowest concentration of volatile
      compounds was observed in Ohio clover honey followed by Indiana clover honey.
      PRACTICAL APPLICATION: Using chemometrics, concentrations of volatile compounds
      in different honeys can be used to determine the influence of botanical and
      geographical origins on aroma, which is important for the quality of honey.
      Characterization of volatile compounds can also be a useful tool for assessing
      honey quality.

PMID- 22950650
TI  - Alternative female kangaroo care for procedural pain in preterm neonates: a pilot
      study.
AB  - AIM: To determine the feasibility and effect size of kangaroo care (KC) for pain
      from heel lance in preterm neonates provided by either the infant's mother (MKC)
      or an unrelated alternate female (AFKC). METHODS: Using a randomized crossover
      design, preterm neonates (n = 18) between 28 and 37 weeks gestational age within
      10 days of life from two university-affiliated level III NICU's undergoing
      routine heel lance were assigned to receive KC 30 min before and during the
      procedure from either their mother (MKC) or an unrelated woman. In the second
      heel lance procedure at least 24 h later but within 10 days, the infants were
      crossed over to the other condition. RESULTS: There was a 48% participation rate,
      with only 40 of 82 eligible cases having maternal consent. The main reason for
      refusal was discomfort with another woman providing kangaroo care. The effect
      sizes on the pain scores (PIPP) were small, ranging from .23 to .43 across the
      first 2 min of procedure. CONCLUSION: The difference between nonrelated females
      and the mother in decreasing pain response is small, although not negligible.
      Given the high refusal rate, nonrelated females are a less desirable alternative
      to mothers than fathers.

PMID- 22950652
TI  - Cleft palate associated with hairy polyp: a case report.
AB  - Congenital tumors of the oral cavity are extremely uncommon, and hairy polyps are
      rare nonneoplastic growths. Most hairy polyps arise from the oronasopharynx and
      may cause impairment of the upper aerodigestive tract in newborns. Cleft palate
      is one of the most common congenital anomalies but its association with hairy
      polyp has been rarely reported. We report a case of hairy polyp with cleft palate
      and its management. 

PMID- 22950651
TI  - Cryo-thawed embryo transfer: natural versus artificial cycle. A non-inferiority
      trial. (ANTARCTICA trial).
AB  - BACKGROUND: Frozen thawed embryo transfer (FET) is a cost-effective adjunct to
      IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be
      carried out during a period of optimal endometrial receptivity. To optimize
      implantation several methods for endometrium preparation have been proposed. In
      natural cycle FET (NC-FET), the endometrium develops under endogenous hormonal
      stimulation. The development of the dominant follicle and endometrium is
      monitored by ultrasound and FET is timed after triggering ovulation induction or
      determination of the spontaneous LH surge. In an artificial cycle FET (AC-FET)
      estrogens and progesterone are administered to prepare the endometrium for
      implantation. While the currently available data show no significant difference
      in pregnancy rates between these methods, well designed randomized controlled
      trials are lacking. Moreover there is little literature on difference in
      cancellation rates, cost-efficiency and adverse events. METHODS AND DESIGN: In
      this randomized, multi-centre, non-inferiority trial we aim to test the
      hypothesis that there is no significant difference in live birth rates between
      patients undergoing NC-FET versus AC-FET. The primary outcome will be live birth
      rate per embryo transfer procedure. Secondary outcomes will be ongoing and
      clinical pregnancy rate, cancellation rate, (serious) adverse events and cost
      efficiency. Based on a live birth rate of 20% and a minimal clinical important
      difference of 7.5% (one-sided alpha 2.5%, beta 20%) a total of 1150 patients will
      be needed. Analyzes will be performed using both per protocol as well as
      intention to treat analyses. DISCUSSION: This prospective, randomized, non
      inferiority trial aims to address the hypothesis that there is no significant
      difference in live birth rates between patients undergoing NC-FET versus patients
      undergoing AC-FET. Moreover it addresses cost-efficiency as well as the perceived
      burden of both treatments. TRIAL REGISTER: Netherlands trial register (NTR):
      1586.

PMID- 22950653
TI  - Uniform amorphous lactose microspheres formed in simultaneous convective and
      dehydration antisolvent precipitation under atmospheric conditions.
AB  - A simultaneous convection-dehydration and antisolvent precipitation approach has
      been shown to produce uniform microsized lactose particles from aqueous droplet
      at atmospheric pressure. Microparticles with high uniformity having diameters of
      between 1.0 and 2.4 MUm have been obtained. The precipitation of the
      microparticles is driven by a unique self-assembly mechanism that cannot be fully
      elucidated by supersaturation alone. Further analysis suggests that structural
      changes in the solvent/antisolvent mixture, due to hydrophobic hydration, could
      play a role in the precipitation process observed.

PMID- 22950654
TI  - Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first-time-in
      human single-dose study.
AB  - AIMS: Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the
      final step in triacylglycerol (TAG) assembly, is suggested as a treatment for
      type 2 diabetes and obesity based on animal data indicating insulin sensitization
      and weight reduction. This first-time-in-human single ascending dose study
      explored the safety, tolerability, pharmacokinetics and pharmacodynamics of the
      selective DGAT1 inhibitor AZD7687. METHODS: Eighty healthy male subjects were
      enrolled. In each of 10 cohorts, six subjects received the same dose of AZD7687
      orally (range across cohorts 1-60 mg) and two placebo. Plasma AZD7687 exposure
      was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h
      after a standardized mixed meal with fat energy content of 60% (SMM 60%; five
      cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut
      DGAT1 activity. RESULTS: AZD7687 markedly reduced postprandial TAG excursion with
      a steep concentration-effect relationship. Incremental TAG AUC (area under the
      serum concentration vs. time curve) following SMM 60% was decreased >75% from
      baseline at doses >=5 mg (p < 0.0001 vs. placebo). Serum levels of
      diacylglycerol, specifically measured with mass spectrometry, did not increase
      after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with
      increasing doses and they limited dose escalation. Lowering of SMM fat content to
      45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal
      symptoms at a given dose of AZD7687. CONCLUSIONS: The attenuating effect of
      AZD7687 on postprandial TAG excursion provides proof of mechanism with respect to
      gut DGAT1 inhibition. However, dose and diet-related gastrointestinal side
      effects may impact further development of DGAT1 inhibitors.

PMID- 22950655
TI  - Knowledge, attitudes and misconceptions of primary care physicians regarding
      fever in children: a cross sectional study.
AB  - BACKGROUND: Fever is an extremely common sign in paediatric patients and the most
      common cause for a child to be taken to the doctor. The literature indicates that
      physicians and parents have too many misconceptions and conflicting results about
      fever management. In this study we aim to identify knowledge, attitudes and
      misconceptions of primary care physicians regarding fever in children. METHODS:
      This cross-sectional study was conducted in April-May 2010 involving primary care
      physicians (n=80). The physicians were surveyed using a self-administered
      questionnaire. Descriptive statistics were used. RESULTS: In our study only 10%
      of the physicians knew that a body temperature of above 37.2  degrees C according
      to an auxiliary measurement is defined as fever. Only 26.2% of the physicians
      took into consideration signs and symptoms other than fever to prescribe
      antipyretics. 85% of the physicians prescribed antipyretics to control fever or
      prevent complications of fever especially febrile seizures. Most of the
      physicians (76.3%) in this study reported that the height of fever may be used as
      an indicator for severe bacterial infection. A great majority of physicians
      (91.3%) stated that they advised parents to alternate the use of ibuprofen and
      paracetamol. CONCLUSIONS: There were misconceptions about the management and
      complications of fever. There is a perceived need to improve the recognition,
      assessment, and management of fever with regards to underlying illnesses in
      children.

PMID- 22950656
TI  - Caffeic acid phenethyl ester protects kidneys against acetylsalicylic acid
      toxicity in rats.
AB  - AIM: The aim of this study was to investigate the protective effect of caffeic
      acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in
      rats. MATERIALS AND METHODS: A total of 40 rats were randomly divided into five
      groups, with eight rats in each group-group 1: control, not receiving any
      medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20
      MUg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) +
      CAPE (20 MUg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days.
      The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase
      1 (PON-1) activity of the blood samples and kidney tissues were determined.
      Histopathological examinations of the kidneys were performed using light
      microscopic methods. RESULTS: The TOS level in the serum of rats and kidney
      tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC
      and PON-1 in these tissues significantly decreased in group 4 when compared with
      the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues
      increased and the levels of TOS decreased in the CAPE treatment groups (groups 3
      and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and
      4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when
      compared to group 4 (p < 0.05). These results were supported by histopathological
      observation. CONCLUSION: Oxidative stress plays an important role in ASA-induced
      nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

PMID- 22950657
TI  - Development and validation of the Yin deficiency scale.
AB  - OBJECTIVES: Yin Deficiency (YD) is a pathophysiologic pattern that manifests with
      emaciation, dry mouth, tidal fever, Five Center Heat, night sweats, and malar
      flushing. The purpose of the present study was to develop and validate a new YD
      metric, the Yin Deficiency Scale (YDS), to define an optimum cutoff point for the
      YDS, and to examine the relationships between YD and Cold-Heat patterns. METHODS:
      A total of 169 outpatients and 83 college students were asked to complete the
      YDS. The college students were also asked to complete the Yin Deficiency
      Questionnaire (YDQ) and Cold-Heat Questionnaire (CHQ). Twelve clinicians
      determined whether or not the 169 outpatients had YD. YDS and YDQ data were used
      to estimate the internal consistency, construct validity, and concurrent validity
      of the YDS. CHQ data were used to examine the relationships between YDS and CHQ
      subscale scores. Total YDS scores and the clinicians' diagnoses of the
      outpatients were used to define an optimum cutoff score for the YDS. RESULTS: The
      27-item YDS had satisfactory internal consistency (alpha=0.885) and concurrent
      validity, with correlations between the YDS and YDQ subscale scores. A total of
      eight factors were extracted in the test of construct validity, using principal
      component analysis, and the overall variance explained by all factors was 63.1%.
      Among the eight factors, cough, fever, and skin-related factors were associated
      only with Heat pattern, whereas pain, urine, and fatigue-related factors were
      associated with both Cold and Heat patterns. In the receiver operating
      characteristic curve analysis, the sensitivity, specificity, and area under the
      curve of the YDS were 73.7%, 84.8%, and 0.875, respectively. The optimum cutoff
      score was defined as 10 points. CONCLUSIONS: The results of this study suggest
      that the YDS is a reliable and valid instrument for evaluating YD.

PMID- 22950658
TI  - Universal routine HPV vaccination for young girls in Uganda: a review of
      opportunities and potential obstacles.
AB  - This article reviews the existing realities in Uganda to identify opportunities
      and potential obstacles of providing universal routine HPV vaccination to young
      adolescent girls. Cervical cancer is a public health priority in Uganda where it
      contributes to about 50-60% of all female malignancies. It is associated with a
      dismal 5-year relative survival of approximately 20%. With adequate financial
      resources, primary prevention through vaccination is feasible using existing
      education and health infrastructure. Cost-effectiveness studies show that at a
      cost of US$2 per dose, the current vaccines would be cost effective. With optimal
      (>=70%) coverage of the target population, the lifetime risk of cervical cancer
      could be reduced by >50%. Uganda fulfils 4 out of the 5 criteria set by the WHO
      for the introduction of routine HPV vaccination to young adolescent girls. The
      existing political commitment, community support for immunization and the
      favorable laws and policy environment all provide an opportunity that should not
      be missed to introduce this much needed vaccine to the young adolescent girls.
      However, sustainable financing by the government without external assistances
      remains a major obstacle. Also, the existing health delivery systems would
      require strengthening to cope with the delivery of HPV vaccine to a population
      that is normally not targeted for routine vaccination. Given the high incidence
      of cervical cancer and in the absence of a national screening program, universal
      HPV vaccination of Ugandan adolescent girls is critical for cervical cancer
      prevention.

PMID- 22950659
TI  - Synthesis, insecticidal activity, crystal structure, and molecular docking
      studies of nitenpyram analogues with an omega-hydroxyalkyl ester arm anchored on
      the tetrahydropyrimidine ring.
AB  - On the basis of the research of the proposed modes of action between
      neonicotinoids and insect nicotinic acetylcholine receptor (nAChR), a new series
      of nitenpyram analogues with an omega-hydroxyalkyl ester arm anchored on the
      tetrahydropyrimidine ring was designed and synthesized to further enhance the
      strength of the hydrogen-bonding action they display in binding with the nAChR.
      The structures of the target compounds were characterized by (1)H NMR, IR, and
      elemental analysis, and the cis configuration was confirmed by X-ray diffraction.
      Preliminary bioassays indicated that all of the nitenpyram analogues exhibited
      good insecticidal activity against Nilaparvata lugens and Myzus persicae at 100
      mg/L, whereas analogues 4d and 6a afforded the best in vitro activity that had >=
      95% mortality at 4 mg/L; the LC(50) values of the analogues 4d and 6a were 0.170
      and 0.154 mg/L, respectively. Structure-activity relationship (SAR) studies
      suggested that their insecticidal potency was also dual-controlled by the
      flexibility and size of the molecule. In addition, molecular docking simulations
      revealed that analogues 4d and 6a displayed stronger hydrogen-bonding action in
      binding with the nAChR, which explained the SARs observed in vitro and implied
      that the designed nitenpyram analogues are both practical and feasible.

PMID- 22950660
TI  - Effect of luteal-phase support on endometrial microRNA expression following
      controlled ovarian stimulation.
AB  - BACKGROUND: Studies suggested that microRNAs influence cellular activities in the
      uterus including cell differentiation and embryo implantation. In assisted
      reproduction cycles, luteal phase support, given to improve endometrial
      characteristics and to facilitate the implantation process, has been a standard
      practice. The effect of different types of luteal phase support using steroid
      hormones in relation to endometrial miRNA profiles during the peri-implantation
      period has not seen described. This study was designed to evaluate the expression
      of miRNAs during the luteal phase following controlled ovarian stimulation for
      IVF and the influence of different luteal phase support protocols on miRNA
      profiles. METHODS: The study was approved by the Johns Hopkins Hospital
      Institutional Review Board. Endometrial biopsies were obtained on the day of
      oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy
      was obtained 3-5 days later (Group II) after the donors were randomized into
      three groups. Group IIa had no luteal-phase support, group IIb had luteal support
      with micronized progesterone (P), and Group IIc had luteal support with
      progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and
      microarray analysis was performed using an Illumina miRNA expression panel.
      RESULTS: A total of 526 miRNAs were identified. Out of those, 216 miRNAs were
      differentially regulated (p < 0.05) between the comparison groups. As compared to
      the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than
      2 fold in the groups of no support, in the P support only, and in the P + E
      support respectively, 3-5 days after retrieval. During the peri-implantation
      period (3-5 days after retrieval) the expression of 33 and 6 miRNAs increased,
      while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E
      group respectively as compared to the no steroid supplementation group.
      CONCLUSION: Luteal support following COS has a profound influence on miRNA
      profiles. Up or down regulation of miRNAs after P or P + E support suggest a
      role(s) of luteal support in the peri-implantation uterus in IVF cycles through
      the regulation of associated target genes.

PMID- 22950662
TI  - Heat-induced cross-linking and degradation of wheat gluten, serum albumin, and
      mixtures thereof.
AB  - Some wheat-based food systems, such as cakes, cookies, and egg noodles, contain
      mixtures of animal and plant (gluten) proteins and are processed under (mildly)
      alkaline conditions. Although changes in these proteins during processing can
      affect end product quality, they have seldom been studied. This study
      investigated protein cross-linking and degradation during heating (0-120 min, pH
      8.0, 50-130  degrees C) of (mixtures of) wheat gluten and bovine serum albumin
      (BSA). The decrease in protein extractabilities in sodium dodecyl sulfate
      containing buffer under (non)reducing conditions and the levels of (cross-linked)
      amino acids were measured. No indications for polymerization at 50  degrees C
      were found. Below 100  degrees C, BSA polymerized more readily than wheat gluten.
      Above 100  degrees C, the opposite was observed. The kinetics of heat-induced
      polymerization of a 1:1 gluten-BSA mixture were similar to that of isolated
      gluten, implying that gluten decelerated BSA denaturation. Severe heating (130 
      degrees C, >15 min) induced degradation reactions in gluten but not in BSA. At
      all conditions used in this study, disulfide (SS) bonds contributed to the
      extractability loss. In addition, above 110  degrees C, beta-elimination of
      cystine led to non-SS cross-links. Intramolecular SS bonds more often transformed
      in intermolecular non-SS bonds in BSA than in gluten. 

PMID- 22950661
TI  - Investigating the molecular basis of local adaptation to thermal stress:
      population differences in gene expression across the transcriptome of the copepod
      Tigriopus californicus.
AB  - BACKGROUND: Geographic variation in the thermal environment impacts a broad range
      of biochemical and physiological processes and can be a major selective force
      leading to local population adaptation. In the intertidal copepod Tigriopus
      californicus, populations along the coast of California show differences in
      thermal tolerance that are consistent with adaptation, i.e., southern populations
      withstand thermal stresses that are lethal to northern populations. To understand
      the genetic basis of these physiological differences, we use an RNA-seq approach
      to compare genome-wide patterns of gene expression in two populations known to
      differ in thermal tolerance. RESULTS: Observed differences in gene expression
      between the southern (San Diego) and the northern (Santa Cruz) populations
      included both the number of affected loci as well as the identity of these loci.
      However, the most pronounced differences concerned the amplitude of up-regulation
      of genes producing heat shock proteins (Hsps) and genes involved in
      ubiquitination and proteolysis. Among the hsp genes, orthologous pairs show
      markedly different thermal responses as the amplitude of hsp response was greatly
      elevated in the San Diego population, most notably in members of the hsp70 gene
      family. There was no evidence of accelerated evolution at the sequence level for
      hsp genes. Among other sets of genes, cuticle genes were up-regulated in SD but
      down-regulated in SC, and mitochondrial genes were down-regulated in both
      populations. CONCLUSIONS: Marked changes in gene expression were observed in
      response to acute sub-lethal thermal stress in the copepod T. californicus.
      Although some qualitative differences were observed between populations, the most
      pronounced differences involved the magnitude of induction of numerous hsp and
      ubiquitin genes. These differences in gene expression suggest that evolutionary
      divergence in the regulatory pathway(s) involved in acute temperature stress may
      offer at least a partial explanation of population differences in thermal
      tolerance observed in Tigriopus.

PMID- 22950663
TI  - In vivo study of the survival of Lactobacillus delbruecki subsp. bulgaricus CECT
      4005T and Streptococcus thermophilus CECT 801 by DVC-FISH after consumption of
      fermented milk.
AB  - Direct Viable Count (DVC) method has been recently combined with fluorescent in
      situ hybridization (FISH) for the specific detection of viable cells of
      Lactobacillus delbrueckii subsp. bulgaricus CECT 4005T and Streptococcus
      thermophilus CECT 801. This method has been used to determine their in vitro
      viability to gastrointestinal juices, being the resistance of L. delbrueckii
      subsp. bulgaricus and S. thermophilus 26.2% and 9.2%, respectively. On the other
      hand, an in vivo study has been carried out with the application of this
      technique for their detection in human feces, after consuming fermented milk.
      Cells of L. delbrueckii subsp. bulgaricus CECT 4005T were not detected, whereas
      viable cells of S. thermophilus CECT 801 were detected in a number higher than
      10(3)  cells per gram in a 30% of the samples after 4 wk of consumption. DVC-FISH
      is a quick and culture-independent useful method, which has been applied for the
      1st time in an in vivo survival study of LAB.

PMID- 22950665
TI  - Reduced intravenous toxicity of amiodarone nanosuspension in mice and rats.
AB  - The toxicity of amiodarone Lek formulation (test formulation) was investigated
      after a single intravenous (i.v.) administration to mice and rats. When compared
      to the reference item, Cordarone (Cordarone((r)); Wyeth Pharmaceuticals Inc.,
      Collegeville, Pennsylvania, USA), median lethal dose (LD(50)) after i.v.
      administration in female mice was 294.0 mg/kg body weight (b.w.) for the test
      formulation and 227.5 mg/kg b.w. for Cordarone. In female rats after i.v.
      administration, the LD(50) value was 269.9 mg/kg b.w. for the test formulation
      and 192.4 mg/kg b.w. for Cordarone. By altering the particle size of amiodarone
      in the Lek formulation, we were able to improve the solubility of amiodarone,
      thereby decreasing the number and quantity of excipients needed for preparation
      of the i.v. formulation and, consequently, reduced the acute toxic effects
      observed in the present study.

PMID- 22950666
TI  - Depletion-mediated potentials and phase behavior for micelles, macromolecules,
      nanoparticles, and hydrogel particles.
AB  - We report a simple depletion potential that captures measured potentials and
      phase behavior for micrometer-sized colloids in the presence of unadsorbing
      charged micelles, charged nanoparticles, nonionic macromolecules, and nonionic
      hydrogel particles. Total internal reflection microscopy (TIRM) is used to
      measure net potentials between colloids and surfaces, and video microscopy (VM)
      is used to measure quasi-2D phase behavior in the same material systems. A
      modified Asakura-Oosawa (AO) depletion potential is developed to accurately
      quantify particle-wall potentials and interfacial crystallization via particle
      particle potentials in Monte Carlo (MC) simulations. The modified AO potential
      includes effective depletant sizes, accurate osmotic equations of state, and
      partition coefficients. Partition coefficients are used as the sole adjustable
      fitting parameter, although an approach to their theoretical prediction from
      depletant density profiles is also presented. Our results demonstrate a model
      that accurately captures depletion interactions and phase behavior in a variety
      of material systems.

PMID- 22950667
TI  - Lessons learned from a double-blind randomised placebo-controlled study with a
      iota-carrageenan nasal spray as medical device in children with acute symptoms of
      common cold.
AB  - BACKGROUND: Common cold is caused by a variety of respiratory viruses. The
      prevalence in children is high, and it potentially contributes to significant
      morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral
      load in nasal secretions and alleviated symptoms in adults with common cold.
      METHODS: We have assessed the antiviral and therapeutic activity of a nasal spray
      containing iota-carrageenan in children with acute symptoms of common cold. A
      cohort of 153 children between 1-18 years (mean age 5 years), displaying acute
      symptoms of common cold were randomly assigned to treatment with a nasal spray
      containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as
      placebo for seven days. Symptoms of common cold were recorded and the viral load
      of respiratory viruses in nasal secretions was determined at two consecutive
      visits. RESULTS: The results of the present study showed no significant
      difference between the iota carrageenan and the placebo group on the mean of TSS
      between study days 2-7. Secondary endpoints, such as reduced time to clearance of
      disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and
      lower incidence of secondary infections with other respiratory viruses (p =
      0.046) indicated beneficial effects of iota-carrageenan in this population. The
      treatment was safe and well tolerated, with less side effects observed in the
      verum group compared to placebo. CONCLUSION: In this study iota-carrageenan did
      not alleviate symptoms in children with acute symptoms of common cold, but
      significantly reduced viral load in nasal secretions that may have important
      implications for future studies. TRIAL REGISTRATION: ISRCTN52519535,
      http://www.controlled-trials.com/ISRCTN52519535/

PMID- 22950668
TI  - Modification of high saturated fat diet with n-3 polyunsaturated fat improves
      glucose intolerance and vascular dysfunction.
AB  - AIMS: The ability of dietary enrichment with monounsaturated fatty acid (MUFA), n
      3 or n-6 polyunsaturated fatty acids (PUFAs) to reverse glucose intolerance and
      vascular dysfunction resulting from excessive dietary saturated fatty acids is
      not resolved. We hypothesized that partial replacement of dietary saturated fats
      with n-3 PUFA-enriched menhaden oil (MO) would provide greater improvement in
      glucose tolerance and vascular function compared to n-6 enriched safflower oil
      (SO) or MUFA-enriched olive oil (OO). METHODS: We fed mice a high saturated fat
      diet (HF) (60% kcal from lard) for 12 weeks before substituting half the lard
      with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed
      glucose tolerance, insulin signalling and reactivity of isolated pressurized
      gracilis arteries. RESULTS: After 12 weeks of saturated fat diet, body weights
      were elevated and glucose tolerance was abnormal compared to mice on control diet
      (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose
      tolerance and indices of insulin signalling (phosphorylated Akt) to normal,
      whereas restoration was limited for SO and OO substitutions. Although dilation to
      acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared
      to normal diet, dilation to acetylcholine was fully restored and constriction to
      phenylephrine was reduced in MO-fed mice compared to normal. CONCLUSION: We
      conclude that short-term enrichment of an ongoing high fat diet with n-3 PUFA
      rich MO, but not MUFA rich OO or n-6 PUFA rich SO, reverses glucose tolerance,
      insulin signalling and vascular dysfunction.

PMID- 22950669
TI  - Complete mitochondrial genome of Gekko swinhonis (Squamata, Gekkonidae).
AB  - The complete mitochondrial genome sequence of Gekko swinhonis was determined in
      this paper. The genome was 16,818 bp in length and contained 13 protein-coding
      genes, 2 rRNA genes, 22 tRNA genes, and 1 control region (CR). The gene
      composition and order of G. swinhonis were similar to most other squamate
      reptiles. The overall base composition of the genome in descending order was
      31.35% A, 27. 71% C, 26.28% T, and 14.67% G, with a slight AT bias of 57.62%. CR
      is located between the tRNA-Pro and tRNA-Phe genes and is 1456 bp in length; some
      tandem repeat sequences and conserved elements (TAS, CSB1-3) were found in the
      CR.

PMID- 22950670
TI  - Lung adenocarcinoma with Lambert-Eaton myasthenic syndrome indicated by voltage
      gated calcium channel: a case report.
AB  - INTRODUCTION: Lambert-Eaton myasthenic syndrome is a rare disorder and it is
      known as a paraneoplastic neurological syndrome. Small cell lung cancer often
      accompanies this syndrome. Lambert-Eaton myasthenic syndrome associated with lung
      adenocarcinoma is extremely rare; there are only a few reported cases worldwide.
      CASE PRESENTATION: A 75-year-old Japanese man with a past history of chronic
      rheumatoid arthritis and Sjogren syndrome was diagnosed with Lambert-Eaton
      myasthenic syndrome by electromyography and serum anti-P/Q-type voltage-gated
      calcium channel antibody level preceding the diagnosis of lung cancer. A chest
      computed tomography to screen for malignant lesions revealed an abnormal shadow
      in the lung. Although a histopathological examination by bronchoscopic study
      could not reveal the malignancy, lung cancer was mostly suspected after the
      results of a chest computed tomography and [18F]-fluorodeoxyglucose positron
      emission tomography. An intraoperative diagnosis based on the frozen section
      obtained by tumor biopsy was adenocarcinoma so the patient underwent a lobectomy
      of the right lower lobe and lymph node dissection with video-assisted
      thoracoscopic surgery. The permanent pathological examination was the same as the
      frozen diagnosis (pT2aN1M0: Stage IIa: TNM staging 7th edition).
      Immunohistochemistry revealed that most of the cancer cells were positive for P/Q
      type voltage-gated calcium channel. CONCLUSIONS: Our case is a rare combination
      of Lambert-Eaton myasthenic syndrome associated with lung adenocarcinoma,
      rheumatoid arthritis and Sjogren syndrome, and to the best of our knowledge it is
      the first report that indicates the presence of voltage-gated calcium channel in
      lung adenocarcinoma by immunostaining.

PMID- 22950671
TI  - Glutathione export from human erythrocytes and Plasmodium falciparum malaria
      parasites.
AB  - Glutathione export from uninfected human erythrocytes was compared with that from
      cells infected with the malaria parasite Plasmodium falciparum using two separate
      methods that distinguish between oxidized (GSSG) and reduced (GSH) glutathione.
      One involved enzymatic recycling with or without thiol-masking; the other
      involved rapid derivatization followed by HPLC. Glutathione efflux from
      uninfected erythrocytes under physiological conditions occurred predominantly as
      GSH. On exposure of the cells to oxidative challenge, efflux of GSSG exceeded
      that of GSH. Efflux of both species was blocked by MK571, an inhibitor of
      mammalian multidrug-resistance proteins. Glutathione efflux from parasitized
      erythrocytes was substantially greater than that from uninfected erythrocytes.
      Under physiological conditions, the exported species was GSH, whereas under
      energy-depleted conditions, GSSG efflux occurred. Glutathione export from
      parasitized cells was inhibited partially by MK571 and more so by furosemide, an
      inhibitor of the 'new permeability pathways' induced by the parasite in the host
      erythrocyte membrane. Efflux from isolated parasites occurred as GSH. On exposure
      to oxidative challenge, this GSH efflux decreased, but no GSSG export was
      detected. These results are consistent with the view that the parasite supplies
      its host erythrocyte with GSH, much of which is exported from the infected cell
      via parasite-induced pathways.

PMID- 22950672
TI  - Electrochromic properties of inkjet printed vanadium oxide gel on flexible
      polyethylene terephthalate/indium tin oxide electrodes.
AB  - Vanadium oxide gel was synthesized and formulated for the assembly of solid-state
      electrochromic cells on flexible and transparent electrodes using inkjet
      printing. FTIR, Raman, and X-ray diffraction spectroscopic measurements showed
      that the vanadium oxide gel here synthesized consisted of V(2)O(5).6H(2)O,
      microstructures similar to orthorhombic V(2)O(5), while Raman spectroscopy also
      shows the presence of amorphous domains. Atomic force microscopy (AFM) images of
      the thin films printed using an inkjet shows a ribbonlike structure, which is in
      accordance with previous results of the vanadium oxide gels in solution. Solid
      state electrochromic devices were assembled at room temperature using the inkjet
      printed films, without any sinterization step. The electrochemical properties of
      the vanadium oxide gel were characterized by cyclic voltammetry and
      spectroelectrochemistry by visible/NIR absorption spectroscopy (in both liquid
      and solid-state). Several redox steps are observed, which gives rise to a variety
      of color transitions as a function of the applied voltage. The different optical
      properties of the vanadium oxide gel are assigned to different intercalation
      steps of Li(+), leading to different crystalline phases of the gel. The final
      result is a solid-state electrochromic cell showing excellent contrast between
      the redox states, giving rise to colors such as yellow, green, or blue. Color
      space analysis was used to characterize the electrochromic transitions, and while
      absorption spectra showed rather long switching times (up to 100 s), in L*a*b*
      color space coordinates, the switching time is smaller than 30 s. These
      electrochromic cells also have an excellent cycling stability showing high
      reversibility and a cyclability up to more than 30,000 cycles with a degradation
      of 18%.

PMID- 22950673
TI  - Possible mechanisms of action of the hypotensive effect of Annona muricata
      (soursop) in normotensive Sprague-Dawley rats.
AB  - CONTEXT: Annona muricata Linn (Annonaceae) (soursop) is a food plant reported to
      have antihypertensive properties. OBJECTIVE: We investigated the blood pressure
      reducing effect of its aqueous leaf extract and the possible mechanisms that may
      be responsible. METHODS: Intravenous administration of an aqueous leaf extract
      (9.17-48.5 mg/kg) of A. muricata on the mean arterial pressure and heart rate
      were recorded invasively on anaesthetized, normotensive Sprague-Dawley rats.
      Contractile responses of rat aortic rings to the extract (0.5-4.0 mg/mL) were
      studied using standard organ bath techniques. RESULTS: A. muricata (9.17-48.5
      mg/kg) caused significant (p < 0.05) dose-dependent reduction in blood pressure
      without affecting the heart rates. The hypotensive effects were unaffected by
      atropine (2 mg/kg), mepyramine (5 mg/kg), propranolol (1 mg/kg) and L-NAME (5
      mg/kg). A. muricata leaf aqueous extract significantly (p < 0.05) relaxed
      phenylephrine (10(-9)-10(-4) M) and 80 mM KCl induced contractions in endothelium
      intact and denuded aortic rings; and caused a significant (p < 0.05) rightward
      shift of the Ca(2+) dose response curves in Ca(2+)-free Kreb's solution
      containing 0.1 mM EGTA. CONCLUSIONS: The hypotensive effects of A. muricata are
      not mediated through muscarinic, histaminergic, adrenergic and nitric oxide
      pathways, but through peripheral mechanisms involving antagonism of Ca(2+).

PMID- 22950674
TI  - High strength of physical hydrogels based on poly(acrylic acid)-g-poly(ethylene
      glycol) methyl ether: role of chain architecture on hydrogel properties.
AB  - This investigation was to study the connections between polymer branch
      architecture of physical hydrogels and their properties. The bottle-brush-like
      polymer chains of poly(acrylic acid)-g-poly(ethylene glycol) methyl ether (PAA-g
      mPEG) with PAA as backbones and mPEG as branch architecture were synthesized and
      in situ grafted from silica nanoparticles (SNs) to construct hydrogels cross
      linked networks in aqueous solutions. The structural variables to be discussed
      included molecular weight and molar ratio of branch chains, and new aspects of
      the formation mechanism of physical hydrogels with branch structure in the
      absence of organic cross-links were present. The results indicated that the
      differences of polymer chain architecture could be distinguished via their
      different interactions that are present by gelation process and mature gel
      properties, such as gel strength and swelling ratio. The gelation occurred at the
      critical polymer concentration and molecular weight, respectively, and the
      inorganic/organic (SNs/PAA-g-mPEG) nanoparticles began to entangle and construct
      the cross-linking networks afterward. The gel-to-sol transition temperature (T(g
      s)) and radii of SNs that were encapsulated by polymer chains as a function of
      time for chains' disentanglement were monitored according to the observation of
      the dissolution process, and the molecular weight between two consecutive
      entanglements (M(e)) was calculated thereafter. This study showed that the
      introduction of branch chain onto the linear backbone significantly promoted the
      chain interactions and increased entanglement density, which contributed to the
      hydrogels' network integrity and rigidity, thus illustrating greater elongation
      at break and tensile strength than the hydrogels formulated with linear polymer
      chains.

PMID- 22950676
TI  - Generalized two-dimensional perturbation correlation infrared spectroscopy
      reveals mechanisms for the development of surface charge and recalcitrance in
      plant-derived biochars.
AB  - Fundamental knowledge of how biochars develop surface-charge and resistance to
      environmental degradation is crucial to their production for customized
      applications or understanding their functions in the environment. Two-dimensional
      perturbation-based correlation infrared spectroscopy (2D-PCIS) was used to study
      the biochar formation process in three taxonomically different plant biomass,
      under oxygen-limited conditions along a heat-treatment-temperature gradient (HTT;
      200-650  degrees C). Results from 2D-PCIS pointed to the systematic, HTT-induced
      defragmenting of lignocellulose H-bonding network and
      demethylenation/demethylation, oxidation, or dehydroxylation/dehydrogenation of
      lignocellulose fragments as the primary reactions controlling biochar properties
      along the HTT gradient. The cleavage of OH(...)O-type H-bonds, oxidation of free
      primary hydroxyls to carboxyls (carboxylation; HTT <= 500  degrees C), and their
      subsequent dehydrogenation/dehydroxylation (HTT > 500  degrees C) controlled
      surface charge on the biochars; while the dehydrogenation of methylene groups,
      which yielded increasingly condensed structures (R-CH(2)-R ->R?CH-R ->R?C?R),
      controlled biochar recalcitrance. Variations in biochar properties across plant
      biomass type were attributable to taxa-specific transformations. For example,
      apparent inefficiencies in the cleavage of wood-specific H-bonds, and their
      subsequent oxidation to carboxyls, lead to lower surface charge in wood biochars
      (compared to grass biochars). Both nontaxa and taxa-specific transformations
      highlighted by 2D-PCIS could have significant implications for biochar
      functioning in fire-impacted or biochar-amended systems.

PMID- 22950675
TI  - Phylogenetic relationships among Staphylococcus species and refinement of cluster
      groups based on multilocus data.
AB  - BACKGROUND: Estimates of relationships among Staphylococcus species have been
      hampered by poor and inconsistent resolution of phylogenies based largely on
      single gene analyses incorporating only a limited taxon sample. As such, the
      evolutionary relationships and hierarchical classification schemes among species
      have not been confidently established. Here, we address these points through
      analyses of DNA sequence data from multiple loci (16S rRNA gene, dnaJ, rpoB, and
      tuf gene fragments) using multiple Bayesian and maximum likelihood phylogenetic
      approaches that incorporate nearly all recognized Staphylococcus taxa. RESULTS:
      We estimated the phylogeny of fifty-seven Staphylococcus taxa using partitioned
      model Bayesian and maximum likelihood analysis, as well as Bayesian gene-tree
      species-tree methods. Regardless of methodology, we found broad agreement among
      methods that the current cluster groups require revision, although there was some
      disagreement among methods in resolution of higher order relationships. Based on
      our phylogenetic estimates, we propose a refined classification for
      Staphylococcus with species being classified into 15 cluster groups (based on
      molecular data) that adhere to six species groups (based on phenotypic
      properties). CONCLUSIONS: Our findings are in general agreement with gene tree
      based reports of the staphylococcal phylogeny, although we identify multiple
      previously unreported relationships among species. Our results support the
      general importance of such multilocus assessments as a standard in microbial
      studies to more robustly infer relationships among recognized and newly
      discovered lineages.

PMID- 22950678
TI  - Not everything about atrial fibrillation is a hot topic: drug-induced atrial
      fibrillation is an exception.

PMID- 22950677
TI  - Increased proton pump inhibitor and NSAID exposure in irritable bowel syndrome:
      results from a case-control study.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) seen by a
      gastroenterologist often utilize medications that may alter intestinal
      homeostasis. The question arises whether exposure to these drugs is associated
      with the development of IBS symptoms. Aim of this study was therefore to assess
      the use of PPIs and NSAIDs in patients with IBS versus controls. METHODS: Cases
      of IBS from the last 5 years were reviewed. All patients having had at least one
      prescription for a particular drug (PPIs, NSAIDs, SSRIs, diuretics, ACE
      inhibitors) in the 6 months prior to the time of initial symptom onset were
      considered exposed. The control group consisted of individuals randomly selected
      from the general population. RESULTS: 287 cases of IBS were retrieved for
      analysis together with 287 age and sex-matched controls. Exposure to PPIs and
      NSAIDs was significantly higher in IBS patients, whereas no association between
      ACE inhibitor use and IBS was found. PPIs were not significantly associated when
      excluding patients with gastrointestinal reflux disease or functional dyspepsia.
      Exposure to SSRIs was also positively associated with IBS, but only when patients
      with psychiatric comorbidity were included in the analyses. CONCLUSIONS:
      Medications that may alter intestinal homeostasis such as NSAIDs and PPIs were
      more frequently used in IBS patients compared to controls. This association might
      be relevant for everyday clinical practice, but it is remains to be elucidated
      whether this association is of etiological nature.

PMID- 22950679
TI  - Site-selective electrophilic cyclization and subsequent ring-opening: a synthetic
      route to pyrrolo[1,2-a]quinolines and indolizines.
AB  - An efficient strategy for the synthesis of pyrrolo[1,2-a]quinolines and
      indolizines from pyranoquinolines via site-selective electrophilic cyclization
      and subsequent opening of pyran ring using silver/iodine under mild reaction
      conditions is described. This approach involves the preferential attack of the
      pyridyl nitrogen over aryl ring and leads to the formation of 5-endo-dig cyclized
      products. Quantum chemical calculations between C-N (DeltaE(a) = 9.01 kcal/mol)
      and C-C (DeltaE(a) = 31.31 kcal/mol) bond formation were performed in order to
      rationalize the observed site selectivity. Structure of the products were
      confirmed by the X-ray crystallographic studies. Iodo-substituted compounds
      generated by the electrophilic iodocyclization were further diversified via Pd
      catalyzed cross-coupling reactions.

PMID- 22950680
TI  - Targeted synthesis of silicomolybdic acid (Keggin acid) inside mesoporous silica
      hollow spheres for Friedel-Crafts alkylation.
AB  - Herein we report an inside-out preinstallation-infusion-hydration method for
      targeted synthesis of Keggin heteropoly acids (silicomolybdic acid,
      H(4)SiMo(12)O(40)) within mesoporous silica (SiO(2)) hollow spheres. In this
      process, discrete molybdenum dioxide (MoO(2)) nanoparticles with diameter size
      ranging from 25 to 60 nm were first prepared by a one-pot hydrothermal route in
      water/ethanol mixed solvents at 180  degrees C, which were then used as cores to
      grow the shell of supramolecular templated silica with tetraethyl orthosilicate
      (TEOS) and hexadecyltrimethyl- ammonium chloride (CTACl) in alkaline solution. By
      thermal treatment of as-synthesized MoO(2)@SiO(2) core-shell spheres, the organic
      template was burned off and mesoporous shell was formed (BET specific surface
      area was as high as 872 m(2)/g). Meanwhile, the encapsulated MoO(2) was oxidized
      to Mo(6+) and infused to the mesoporous silica shells, forming heptamolybdate
      species (Mo(7)O(24)(6-)) uniformly dispersed on the mesopore surfaces of silica,
      while generating void space at the center of spheres. After hydration with water,
      H(4)SiMo(12)O(40) was formed by reaction between the surface Mo(7)O(24)(6-) and
      silica species in the presence of water. The prepared H(4)SiMo(12)O(40) @mSiO(2)
      hollow spheres were tested for Friedel-Crafts alkylation of toluene by benzyl
      alcohol. The H(4)SiMo(12)O(40)@mSiO(2) catalysts fabricated via this novel route
      exhibited excellent catalytic activity toward benzylation of toluene, which was
      approximately 2.6 times as high as that of commercial Amberlyst-15 catalyst. In
      addition, the H(4)SiMo(12)O(40)@mSiO(2) catalyst was very robust and could be
      reused after regeneration.

PMID- 22950681
TI  - Venous thromboembolism risk and prophylaxis in the acute hospital care setting:
      report from the ENDORSE study in Egypt.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of hospital-related
      deaths worldwide. However, the proportion of patients at risk of VTE who receive
      appropriate prophylaxis in Egypt is unknown. The ENDORSE study in Egypt is part
      of a global initiative to uncover the incidence of high-risk surgical and medical
      patients and determine what proportion of these patients receive appropriate VTE
      prophylaxis. METHODS: Ten Egyptian hospitals participated in this observational
      study, enrolling all surgical and medical patients that met the study criteria.
      This resulted in a cohort of 1,008 patients in acute care facilities who
      underwent a retrospective chart review. Each patient's VTE risk status and the
      presence or absence of appropriate prophylactic care was assessed according to
      the American College of Chest Physicians (ACCP) guidelines 2004. RESULTS: Of the
      1,008 patients enrolled, 395 (39.2%) were found to be at high-risk for VTE.
      Overall, 227 surgical patients were at high-risk, although only 80 (35.2%)
      received ACCP-recommended prophylaxis. Similarly, 55/268 (32.75%) of high-risk
      medical patients received appropriate VTE prophylaxis. Low molecular weight
      heparin was the most commonly used anticoagulant, while mechanical prophylactic
      use was quite low (1.5%) in high-risk patients. CONCLUSIONS: In Egypt, more than
      one-third of all patients hospitalized for surgery or acute medical conditions
      are at high risk for developing VTE. However, only a small fraction of these
      patients receive appropriate VTE prophylaxis. Corrective measures are necessary
      for preventing VTE morbidity and mortality in these high risk patients.

PMID- 22950682
TI  - Biology of Culex sitiens, a predominant mosquito in Phang Nga, Thailand after a
      tsunami.
AB  - A tsunami affected area in Phang Nga province, Thailand was explored randomly as
      some freshwater sites had changed into brackish-water sites. A survey of four
      areas found Culex sitiens to be the most dominant mosquito species.This mosquito
      prefers to breed in putrefied water with garbage and it was found in almost every
      stagnant, brackish-water site in full sunlight. The larval density was more than
      300 larvae/dip/250 ml water. Its biting cycle, determined by human landing catch,
      was nocturnal, with a single peak at 19.00-20.00 hr. The maximum rate was 108
      mosquitoes per person/hour. The biology of the mosquito was studied by
      colonization in natural water under laboratory conditions. The mean number of
      eggs per raft was 158.1 +/- 31.7, hatchability 96.6 +/- 4.1%, development from
      1st instar larvae to adult was 8.8-11.7 days, and longevity of adult males was
      7.3-41.3 days and females 11.0-52.7 days. The ratio of adult males to adult
      females was 1:1.1 +/- 0.2.

PMID- 22950683
TI  - Effect of germination temperatures on proteolysis of the gluten-free grains rice
      and buckwheat during malting and mashing.
AB  - This study examined the performance of rice and buckwheat when malted under
      various temperature conditions and for different lengths of time. The mashed
      malts produced from both rice and buckwheat contained a wide spectra of sugars
      and amino acids that are required for yeast fermentation, regardless of malting
      temperature. At the germination temperatures of 20, 25, and 30  degrees C used,
      production of reducing sugars and free amino nitrogen (FAN) followed similar
      patterns. This implies that temperature variations, experienced in different
      countries, will not have an adverse effect on the production and release of amino
      acids and sugars, required by yeast during fermentation, from these grains. Such
      consistency in the availability of yeast substrates is likely to reduce
      differences in processing when these malts are used for brewing. This study
      revealed that, while rice malt consistently produced more maltose than glucose,
      buckwheat malt gave several times more glucose than maltose, across all
      germination temperatures. Buckwheat malt also produced more soluble and free
      amino nitrogen than rice malt. Unlike sorghum, which has gained wide application
      in the brewing industry for the production of gluten-free beer, the use of rice
      and buckwheat is minimal. This study provides novel information regarding the
      potential of rice and buckwheat for brewing. Both followed similar patterns to
      sorghum, suggesting that they could play a similar role to sorghum in the brewing
      industry. Inclusion of rice and buckwheat as brewing raw materials will increase
      the availability of suitable materials for use in the production of gluten-free
      beer, potentially making it more sustainable, cheaper, and more widely available.

PMID- 22950684
TI  - Adsorption characteristics of fungal family 1 cellulose-binding domain from
      Trichoderma reesei cellobiohydrolase I on crystalline cellulose: negative
      cooperative adsorption via a steric exclusion effect.
AB  - Cellobiohydrolases (CBHs) hydrolyzing crystalline cellulose share a two-domain
      structure of catalytic domain (CD) and cellulose-binding domain (CBD). To focus
      on the binding characteristics of CBD, we analyzed the adsorption of fusion
      protein of fungal family 1 CBD from  Trichoderma reesei  CBH I and red
      fluorescent protein on crystalline and amorphous celluloses. Binding data were
      better fitted by Hill's model with negative cooperativity than by other
      adsorption models, suggesting the occurrence of a steric exclusion effect among
      the fusion molecules on the cellulose surfaces. The degree of negative
      cooperativity depended on the nature of the cellulose. The significance of this
      phenomenon for catalysis by intact CBHI is discussed.

PMID- 22950685
TI  - Recombinant erythropoietin for the anaemia of patients with advanced
      Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only
      in non progressive patients.
AB  - Recombinant erythropoietin for the anaemia of patients with advanced
      Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only
      in non progressive patients. BACKGROUND: Imatinib is a standard treatment for
      advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed
      in patients with advanced GIST, and is one of the most frequent side effects of
      imatinib with grade 3-4 anaemia in 10% of patients. Whether EPO treatment is
      useful in the management of GIST patients receiving imatinib treatment is
      unknown. METHODS: A retrospective study of EPO treatment in GIST patients
      receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO
      treatment among the 319 GIST patients treated with imatinib in clinical trials or
      with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia
      of patients with GIST treated with imatinib was analyzed. RESULTS: There were 18
      males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary
      tumour sites were mainly gastric (32%) and small bowel (29%). Sites of metastases
      were mainly liver (82%) and peritoneum (79%). The median delay between the
      initiation of imatinib treatment and EPO was 58 days (range 0-553). Median
      haemoglobin (Hb) level prior to EPO was 9 g/dL (range 6,9-11,8) and 11,7 g/dL
      (range 6,8-14,4) after 2 months. An increase of more than 2 g/dL was observed in
      18 (53%) of patients. None of the 7 patients who progressed (PD) under imatinib
      treatment (400 mg/day) experienced HB response, as compared to 66% (18/27) of the
      remaining patients (PR + SD) (p = 0,002). Primary tumour site, liver metastases,
      peritoneal metastases, age, gender did not correlate with HB response to EPO.
      Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800
      mg/day) vs 16/23 of others. Using logistic regression, only PD before EPO
      treatment was retained as a predictive factor for EPO response. CONCLUSION: EPO
      enables to increase Hb in most anaemic GIST patients who do not progress under
      imatinib, but not in patients with progressive disease.

PMID- 22950686
TI  - Developing open source, self-contained disease surveillance software applications
      for use in resource-limited settings.
AB  - BACKGROUND: Emerging public health threats often originate in resource-limited
      countries. In recognition of this fact, the World Health Organization issued
      revised International Health Regulations in 2005, which call for significantly
      increased reporting and response capabilities for all signatory nations.
      Electronic biosurveillance systems can improve the timeliness of public health
      data collection, aid in the early detection of and response to disease outbreaks,
      and enhance situational awareness. METHODS: As components of its Suite for
      Automated Global bioSurveillance (SAGES) program, The Johns Hopkins University
      Applied Physics Laboratory developed two open-source, electronic biosurveillance
      systems for use in resource-limited settings. OpenESSENCE provides web-based data
      entry, analysis, and reporting. ESSENCE Desktop Edition provides similar
      capabilities for settings without internet access. Both systems may be configured
      to collect data using locally available cell phone technologies. RESULTS: ESSENCE
      Desktop Edition has been deployed for two years in the Republic of the
      Philippines. Local health clinics have rapidly adopted the new technology to
      provide daily reporting, thus eliminating the two-to-three week data lag of the
      previous paper-based system. CONCLUSIONS: OpenESSENCE and ESSENCE Desktop Edition
      are two open-source software products with the capability of significantly
      improving disease surveillance in a wide range of resource-limited settings.
      These products, and other emerging surveillance technologies, can assist resource
      limited countries compliance with the revised International Health Regulations.

PMID- 22950687
TI  - Identifying novel biomarkers for cardiovascular disease risk prediction.
AB  - The primary prevention of cardiovascular disease relies on the ability to
      identify at-risk individuals long before the development of overt events. In the
      past decade, research into circulating, genetic and imaging biomarkers to augment
      traditional methods of risk prediction has only achieved modest success. Emerging
      technologies in the fields of genomics, metabolomics and proteomics are providing
      new platforms for biomarker discovery. Here, we review current concepts in the
      evaluation and discovery of cardiovascular biomarkers. Further research is needed
      to identify new biomarkers to successfully stratify risk of cardiovascular
      disease in low-risk populations, as well as to test whether management strategies
      informed by biomarker testing are better than standard of care.

PMID- 22950688
TI  - Commentary on: Tse R, Langlois N, Winskog C, Byard RW. An assessment of the
      usefulness of routine histological examination in hanging deaths. J Forensic Sci
      2012;57(4):976-8.

PMID- 22950690
TI  - Commentary on: Feltracco P, Barbieri S, Galligioni H, Pasin L, Gaudio RM, Tommasi
      A, et al. A fatal case of anaphylactic shock during paragliding. J Forensic Sci
      2012; doi: 10.1111/j.1556-4029.2012.02187.x [Epub ahead of print].

PMID- 22950692
TI  - Commentary on: Inoue K, Fukunaga T, Okazaki Y. Study of an economic issue as a
      possible indicator of suicide risk. J Forensic Sci 2012;57(3):783-5.

PMID- 22950694
TI  - Commentary on: Levi-Faict TW, Quatrehomme G. So-called spontaneous human
      combustion. J Forensic Sci 2011;56(5):1334-39.

PMID- 22950696
TI  - Commentary on: Kunz SN, Zinka B, Fieseler S, Graw M, Peschel O. Functioning and
      effectiveness of electronic control devices such as the TASER(r) M- and X-Series:
      a review of the current literature. J Forensic Sci 2012; doi: 10.1111/j.1556
      4029.2012.02167.x [Epub ahead of print].

PMID- 22950698
TI  - Commentary on: Chi JH. Metallographic analysis and fire dynamics simulation for
      electrical fire scene reconstruction. J Forensic Sci 2012;57(1):246-9.

PMID- 22950700
TI  - Commentary on: Akyildiz E, Uzun I, Inanici MA, Baloglu H. Computerized image
      analysis in differentiation of skin lesion caused by electrocution, flame burns,
      and abrasion. J Forensic Sci 2009;54(6):1419-22.

PMID- 22950701
TI  - The protective effects of omega 3 fatty acids and sesame oil against cyclosporine
      A-induced nephrotoxicity.
AB  - Cyclosporine A (CsA) is a drug used in autoimmune disorders and organ
      transplantations. Omega 3 fatty acids (O-3) and sesame oil (SO) have antioxidant
      properties. We aimed to investigate and compare the protective effects of O-3 and
      SO against CsA-induced nephrotoxicity. Seven groups of male Wistar albino rats
      were included in the study. In group 1 (control), saline was administered, and in
      group 2, CsA (subcutaneously) was administered. In group 3, CsA+SO (orally; p.o.)
      was given; in group 4, CsA+O-3 (p.o.) was given; and in group 5, CsA+SO+O-3 was
      given. In group 6, SO was administered, and in group 7, O-3 was administered.
      After 15 days of treatment, kidneys were excised. Histopathological evaluation,
      apoptotic cell count, and renal/hepatic function tests were performed. In group
      2, vacuolar degeneration and necrosis of tubular cells as well as hemorrhagic
      foci were observed; the apoptotic cell number was higher than in the control (P <
      0.001). In groups 3, 4, and 5, tubular scores and apoptotic cell count were lower
      than in group 2 (P < 0.01 and P < 0.001, respectively). In groups 6 and 7,
      healthy renal histology and a few apoptotic cells were determined. In groups 2,
      3, 4, and 5, blood urea nitrogen was higher and albumin was lower than in the
      control (P < 0.001). Liver enzymes were unchanged. O-3/SO showed similar
      protective effects against CsA-induced nephrotoxicity, as revealed by a
      remarkable decrease in histopathological changes and apoptotic cell count.
      However, impaired renal function tests were not improved with O-3/SO treatment.
      SO and O-3 can be used as chemoprotectants against CsA.

PMID- 22950703
TI  - Complete mitochondrial genome of the ring-necked pheasant, Phasianus colchicus
      (Galliformes: Phasianidae).
AB  - The complete mitochondrial genome of Phasianus colchicus is 16,692 bp in length
      and composed of 13 typical protein-coding genes, 22 transfer RNA (tRNA) genes, 2
      ribosomal RNA (rRNA) genes, and 1 putative control region. One extra nucleotide
      "C" is present in nad3 of P. colchicus, which is found in many other birds and is
      thought not to be translated. All protein-coding, rRNA, and tRNA genes have more
      than 99.0% nucleotide sequence similarity with the previously reported
      individual, except for cox3 and tRNA (Pro) genes which has more similarity with
      Phasianus versicolor.

PMID- 22950702
TI  - Vildagliptin preserves the mass and function of pancreatic beta cells via the
      developmental regulation and suppression of oxidative and endoplasmic reticulum
      stress in a mouse model of diabetes.
AB  - AIM: We investigated the molecular mechanisms by which vildagliptin preserved
      pancreatic beta cell mass and function. METHODS: Morphological, biochemical and
      gene expression profiles of the pancreatic islets were investigated in male KK
      A(y) -TaJcl(KK-A(y) ) and C57BL/6JJcl (B6) mice aged 8 weeks which received
      either vildagliptin or a vehicle for 4 weeks. RESULTS: Body weight, food intake,
      fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were
      unchanged with vildagliptin treatment in both mice. In KK-A(y) mice treated with
      vildagliptin, increased plasma triglyceride (TG) level and islet TG content were
      decreased, insulin sensitivity significantly improved, and the glucose tolerance
      ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin
      increased glucose-stimulated insulin secretion, islet insulin content and
      pancreatic beta cell mass in both strains. By vildagliptin, the expression of
      genes involved in cell differentiation/proliferation was upregulated in both
      strains, those related to apoptosis, endoplasmic reticulum stress and lipid
      synthesis was decreased and those related to anti-apoptosis and anti-oxidative
      stress was upregulated, in KK-A(y) mice. The morphological results were
      consistent with the gene expression profiles. CONCLUSION: Vildagliptin increases
      beta cell mass by not only directly affecting cell kinetics but also by
      indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum
      stress in diabetic mice.

PMID- 22950704
TI  - Simultaneous SNP identification and assessment of allele-specific bias from ChIP
      seq data.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) have been associated with many
      aspects of human development and disease, and many non-coding SNPs associated
      with disease risk are presumed to affect gene regulation. We have previously
      shown that SNPs within transcription factor binding sites can affect
      transcription factor binding in an allele-specific and heritable manner. However,
      such analysis has relied on prior whole-genome genotypes provided by large
      external projects such as HapMap and the 1000 Genomes Project. This requirement
      limits the study of allele-specific effects of SNPs in primary patient samples
      from diseases of interest, where complete genotypes are not readily available.
      RESULTS: In this study, we show that we are able to identify SNPs de novo and
      accurately from ChIP-seq data generated in the ENCODE Project. Our de novo
      identified SNPs from ChIP-seq data are highly concordant with published
      genotypes. Independent experimental verification of more than 100 sites estimates
      our false discovery rate at less than 5%. Analysis of transcription factor
      binding at de novo identified SNPs revealed widespread heritable allele-specific
      binding, confirming previous observations. SNPs identified from ChIP-seq datasets
      were significantly enriched for disease-associated variants, and we identified
      dozens of allele-specific binding events in non-coding regions that could
      distinguish between disease and normal haplotypes. CONCLUSIONS: Our approach
      combines SNP discovery, genotyping and allele-specific analysis, but is
      selectively focused on functional regulatory elements occupied by transcription
      factors or epigenetic marks, and will therefore be valuable for identifying the
      functional regulatory consequences of non-coding SNPs in primary disease samples.

PMID- 22950706
TI  - Celebrating the scientific life of Richard A. Mathies.

PMID- 22950705
TI  - Magnetic resonance imaging findings in primary lymphoma of the liver: a case
      report.
AB  - INTRODUCTION: Primary lymphoma of the liver is an extremely rare finding, with
      the few such cases reported in the literature to date describing indeterminate
      imaging findings, being focused more on computed tomography. To the best of our
      knowledge, there is no prior report describing magnetic resonance imaging scan
      findings with such a lesion. In the case reported here, magnetic resonance
      imaging gave us the opportunity to ascertain the correct diagnosis, confirmed by
      histopathology, thus avoiding unnecessary surgery or other treatments. Although
      this condition is rare, knowledge of magnetic resonance imaging findings will be
      invaluable for radiologists and other medical subspecialties that may face such
      cases in the future in helping to provide adequate management for affected
      patients. CASE PRESENTATION: A focal lesion was incidentally detected by
      ultrasound in a 75-year-old asymptomatic Albanian man being treated for benign
      hypertrophy of prostate. Chest and abdomen computed tomography scans did not
      reveal any abnormal findings besides a solid focal lesion on the right lobe of
      the liver and a mild homogenous enlargement of the prostate gland. Subsequently,
      magnetic resonance imaging of the upper abdomen was performed for better
      characterization of this lesion. Our patient was free of symptoms and his
      laboratory test results were normal. CONCLUSIONS: The magnetic resonance imaging
      scan results showed some distinctive features that helped us to make the correct
      diagnosis, and were thus very important in helping us provide the correct
      treatment for our patient.

PMID- 22950709
TI  - Publications of Richard A. Mathies.

PMID- 22950710
TI  - In vitro and in vivo anticancer properties of cucurbitacin isolated from
      Cayaponia racemosa.
AB  - CONTEXT: Cucurbitacins are a group of triterpenoids that have a cucurbitane
      skeleton with a wide range of biological activities. OBJECTIVES: This study
      evaluated the anticancer properties of one cucurbitacin isolated from Cayaponia
      racemosa Cong. (Cucurbitaceae), 2beta,3beta,16alpha,20(R),25-pentahydroxy-22
      oxocucurbita-5-en (1), with in vitro and in vivo models. MATERIALS AND METHODS:
      In vitro cytotoxic activity was determined with human leukemia (HL60) and normal
      blood cells (PBMC). Sarcoma 180 was used as in vivo model. RESULTS: The
      cucurbitacin (1) reduced the number of viable cells; however, there was no
      changed in the number of non-viable cells at 5 ug/mL. Selectivity towards cancer
      cells was suggested by the absence of activity on normal proliferating
      lymphocytes at the concentrations tested (IC50 >25 ug/ml). Morphological analysis
      of compound 1-treated cells showed typical apoptotic features, such as intense
      deposition of granules in the cytoplasm (eosinophilia), DNA fragmentation and
      irregularities in the plasma membrane. In addition, the cells treated with
      compound 1 presented intense vacuolization and disruption of the plasma membrane.
      Acridine orange/Ethidium bromide staining confirmed these findings, revealing an
      increased number of apoptotic cells. In the Sarcoma 180 tumor model, compound 1
      showed 52 and 62% of antitumor activity, either alone (25 mg/kg/day) or in
      association with the chemotherapeutic agent 5-FU (10 + 10 mg/kg/day),
      respectively. Moreover, either alone or associated with 5-FU, treatment with
      compound 1 caused an increase in spleen weight and morphological alterations
      related to immunostimulatory properties. CONCLUSION: These data indicate that
      these naturally occurring compounds have anticancer potential.

PMID- 22950711
TI  - Rationale and design of a double-blind, placebo-controlled, randomized trial to
      evaluate the safety and efficacy of nimodipine in preventing cognitive impairment
      in ischemic cerebrovascular events (NICE).
AB  - BACKGROUND: Stroke is the second most common cause of mortality and the leading
      cause of neurological disability, cognitive impairment and dementia worldwide.
      Nimodipine is a dihydropyridinic calcium antagonist with a role in
      neuroprotection, making it a promising therapy for vascular cognitive impairment
      and dementia. METHODS/DESIGN: The NICE study is a multicenter, randomized, double
      blind, placebo-controlled study being carried out in 23 centers in China. The
      study population includes patients aged 30-80 who have suffered an ischemic
      stroke (<=7 days). Participants are randomly allocated to nimodipine (90 mg/d) or
      placebo (90 mg/d). The primary efficacy is to evaluate the level of mild
      cognitive impairment following treatment of an ischemic stroke with nimodipine or
      placebo for 6 months. Safety is being assessed by observing side effects of
      nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are
      required in this study to obtain statistical power of 90%. The first patient was
      recruited in November 2010. DISCUSSION: Previous studies suggested that
      nimodipine could improve cognitive function in vascular dementia and Alzheimer's
      disease dementia. It is unclear that at which time-point intervention with
      nimodipine should occur. Therefore, the NICE study is designed to evaluate the
      benefits and safety of nimodipine, which was adminstered within seven days, in
      preventing/treating mild cognitive impairment following ischemic stroke.

PMID- 22950712
TI  - Polymorphism in the barley granule bound starch synthase 1 (gbss1) gene
      associated with grain starch variant amylose concentration.
AB  - Granule bound starch synthase 1 (GBSS1) accumulation within starch granules and
      structure of Gbss1 alleles were determined for nine barley ( Hordeum vulgare L.)
      genotypes producing amylose-free (undetectable), near-waxy (1.6-4.5%), normal
      (25.8%), and increased (38.0-40.8%) amylose grain starches. Compared to normal
      starch granules, GBSS1 accumulation was severely reduced in three near-waxy,
      slightly reduced in two waxy, and slightly elevated in three increased amylose
      starches. Gbss1 nucleotide sequence analysis for the nine genotypes distinguished
      them into three Gbss1 groups with several single-nucleotide polymorphisms. A new
      unique Q312H substitution within GBSS1 was discovered in near-waxy genotype
      SB94912 with reduced amylose (1.6%) concentration relative to the other two near
      waxy lines, CDC Rattan and CDC Candle (4.5%). The two waxy genotype GBSS1 showed
      a previously described D287V change for CDC Alamo and a new G513W change for CDC
      Fibar. Both amino acid alterations are conserved residues within starch synthase
      domains involved in glucan interaction. The increased amylose genotypes showed
      several unique nucleotide changes within the second and fourth Gbss1 introns, but
      only SB94893 GBSS1 showed a unique amino acid substitution, A250T in exon 6. The
      Gbss1 nucleotide differences were used to design genetic markers to monitor Gbss1
      alleles in genotypes with various amylose grain starches. 

PMID- 22950713
TI  - Social meanings and understandings in patient-nurse interaction in the community
      practice setting: a grounded theory study.
AB  - BACKGROUND: The patient-nurse relationship is a traditional concern of
      healthcare research. However, patient-nurse interaction is under examined from a
      social perspective. Current research focuses mostly on specific contexts of care
      delivery and experience related to medical condition or illness, or to nurses'
      speciality. Consequentially, this paper is about the social meanings and
      understandings at play within situated patient-nurse interaction in the community
      practice setting in a transforming healthcare service. METHODS: Grounded theory
      methodology was used and the research process was characterised by principles of
      theoretical sensitivity and constant comparative analysis. The field of study was
      four health centres in the community. The participants were patients and nurses
      representative of those attending or working in the health centres and meeting
      there by scheduled appointment. Data collection methods were observations,
      informal interviews and semi-structured interviews. RESULTS: Key properties of
      'Being a good patient, being a good nurse', 'Institutional experiences' and
      'Expectations about healthcare' were associated with the construction of a
      category entitled 'Experience'. Those key properties captured that in an evolving
      healthcare environment individuals continually re-constructed their reality of
      being a patient or nurse as they endeavoured to perform appropriately;
      articulation of past and present healthcare experiences was important in that
      process. Modus operandi in role as patient was influenced by past experiences in
      healthcare and by those in non-healthcare institutions in terms of engagement and
      involvement (or not) in interaction. Patients' expectations about interaction in
      healthcare included some uncertainly as they strived to make sense of the
      changing roles and expertise of nurses and, differentiating between the roles and
      expertise of nurses and doctors. CONCLUSIONS: The importance of social meanings
      and understandings in patient-nurse interaction is not fully apparent to nurses,
      but important in the patient experience. Seeking understanding from a social
      perspective makes a contribution to enhancing knowledge about patient-nurse
      interaction with subsequent impact on practice, in particular the development of
      the patient-nurse relationship. The implications are that the meanings and
      understandings patients and nurses generate from experiences beyond and within
      their situated interaction are pivotal to the development of their relationship
      in the transforming community healthcare environment.

PMID- 22950714
TI  - Zinc oxide nanowire photodetectors with single-walled carbon nanotube thin-film
      electrodes.
AB  - In this study, transparent and flexible zinc oxide (ZnO) nanowire ultraviolet
      (UV) photodetectors prepared via a solution-based method in which single-walled
      carbon nanotube (SWNT) thin films were used as transparent electrodes are
      reported. The photoresponse current was found to be in proportion with the ZnO
      nanowire density, and the nanowire density could be tuned to increase the
      photocurrent by a factor of 300. The decay time for the fabricated photodetectors
      was found to be as low as 16 s. This study suggests the possibility of
      fabricating inexpensive, visible-blind UV photodetectors via solution-based
      methods.

PMID- 22950715
TI  - Non-clinical toxicological considerations for pharmaceutical salt selection.
AB  - INTRODUCTION: Over half of all active pharmaceutical ingredients currently
      approved for use in the USA are pharmaceutical salts. The safety assessment of a
      pharmaceutical salt provides additional challenges in addition to those
      encountered when assessing the safety of the free acid or base form of a new
      chemical entity (NCE). The addition of a counter ion may have an impact on
      pharmacokinetics, toxicity, impurity profile and potential route of
      administration. AREAS COVERED: In this review, the toxicologic profiles of
      commonly used counter ions and strategies for supporting the development of novel
      or alternate pharmaceutical salt forms are summarized. Furthermore, the article
      highlights the major concerns that may be encountered by the non-clinical
      toxicologist when considering a novel pharmaceutical salt. EXPERT OPINION: Given
      the large numbers of pharmaceutical salts approved for use in the USA, relatively
      little non-clinical toxicologic data are available for commonly used counter
      ions. This information gap leaves the non-clinical toxicologist with limited
      resources to assess the impact of a counter ion on the toxicologic program for an
      NCE. The data summarized in this review provide a starting point toward a more
      detailed understanding of counter ion-related effects on the toxicity of
      pharmaceutical salts.

PMID- 22950717
TI  - Measurement of time taken by the Formosan termite, Coptotermes formosanus, to
      pass tunnel intersections.
AB  - Subterranean termites build complex tunnel networks below ground for foraging.
      During the foraging activity, termites may encounter a considerable number of
      tunnel intersections. When they encounter the intersections, they spend some time
      gathering information for making a decision regarding their moving direction by
      anntenation. The spent time is likely to be directly connected to the termites'
      survival because depending on the time, the total traveling time taken by the
      termites for transferring food resources from the site of food to their nest can
      vary significantly because of many intersections. In the present study, we
      measured the time spent by a termite to pass an intersection with widths of W(1)
      and W(2) (W(1) and W(2) : 2, 3, or 4 mm); tau(L) , tau(R) , and tau(s) are the
      passing time for turning left, turning right, and going straight, respectively.
      W(1) represents the width of the tunnel in which the termites advanced, and W(2)
      represents the width of the other tunnel encountered by the advancing termites.
      For the combinations of W(1) and W(2), (W(1), W(2) ) = (2, 2), (3, 3), (2, 3),
      (2, 4), (3, 4), and (4, 3), the values of Ttau(L), tau(R), and tau(s) in each
      case were statistically equal. For (W(1), W(2) ) = (3, 2), (4, 2), and (4, 4),
      tau(s) was shorter than tau(R) and tau(R) in each case. The experimental results
      are briefly discussed in relation to the termite foraging efficiency.

PMID- 22950718
TI  - Diagnostic challenges in the older patient.
AB  - Older patients often present with a long, complex history and a clinical picture
      that frequently includes co-morbidities. It is essential that health
      professionals caring for older patients become familiar with common age-related
      changes, and the specific clinical factors that complicate the diagnostic
      process. A case-based approach is taken in this article to explore the diagnostic
      challenges in caring for older patients. Three areas of focus are used: a)
      polypharmacy, b) cognitive issues such as delirium, dementia and depression, and
      c) increased odds of pathologies and chronic illnesses.

PMID- 22950716
TI  - Is intensive counseling in maternity care feasible and effective in promoting
      physical activity among women at risk for gestational diabetes? Secondary
      analysis of a cluster randomized NELLI study in Finland.
AB  - BACKGROUND: Women who are physically active during early pregnancy have notably
      lower odds of developing gestational diabetes than do inactive women. The purpose
      of the intervention was to examine whether intensified physical activity (PA)
      counseling in Finnish maternity care is feasible and effective in promoting
      leisure-time PA (LTPA) among pregnant women at risk of gestational diabetes.
      METHODS: Fourteen municipalities were randomized to intervention (INT) and usual
      care group (UC). Nurses in INT integrated five PA counseling sessions into
      routine maternity visits and offered monthly group meetings on PA instructed by
      physiotherapists. In UC conventional practices were continued. Feasibility
      evaluation included safety (incidence of PA-related adverse events;
      questionnaire), realization (timing and duration of sessions, number of sessions
      missed, attendance at group meetings; systematic record-keeping of the nurses and
      physiotherapists) and applicability (nurses' views; telephone interview).
      Effectiveness outcomes were weekly frequency and duration of total and intensity
      specific LTPA and meeting PA recommendation for health self-reported at 8-12
      (baseline), 26-28 and 36-37 weeks' gestation. Multilevel analysis with
      adjustments was used in testing for between-group differences in PA changes.
      RESULTS: The decrease in the weekly days of total and moderate-to-vigorous
      intensity LTPA was smaller in INT (N = 219) than in UC (N = 180) from baseline to
      the first follow-up (0.1 vs. -1.2, p = 0.040 and -0.2 vs. -1.3, p = 0.016). A
      similar trend was seen in meeting the PA recommendation (-11%-points vs. -28%
      points, p = 0.06). INT did not experience more adverse events classified as
      warning signs to terminate exercise than UC, counseling was implemented as
      planned and viewed positively by the nurses. CONCLUSIONS: Intensified counseling
      had no effects on the duration of total or intensity-specific weekly LTPA.
      However, it was able to reduce the decrease in the weekly frequency of total and
      moderate-to-vigorous-intensity LTPA from baseline to the end of second trimester
      and was feasibly embedded into routine practices. TR

PMID- 22950719
TI  - The effect of monomer order on the hydrolysis of biodegradable poly(lactic-co
      glycolic acid) repeating sequence copolymers.
AB  - The effect of sequence on copolymer properties is rarely studied despite the
      precedent from Nature that monomer order can create materials of significant
      diversity. Poly(lactic-co-glycolic acid) (PLGA), one of the most important
      biodegradable copolymers, is widely used in an unsequenced, random form for both
      drug delivery microparticles and tissue engineering matrices. Sequenced PLGA
      copolymers have been synthesized and fabricated into microparticles to study how
      their hydrolysis rates compare to those of random copolymers. Sequenced PLGA
      microparticles were found to degrade at slower, and often more constant, rates
      than random copolymers with the same lactic to glycolic acid ratios as
      demonstrated by molecular weight decrease, lactic acid release, and thermal
      property analyses. The impact of copolymer sequence on in vitro release was
      studied using PLGA microparticles loaded with model agent rhodamine-B. These
      assays established that copolymer sequence affects the rate of release and that a
      more gradual burst release can be achieved using sequenced copolymers compared to
      a random control.

PMID- 22950720
TI  - Utilizing carbon dioxide as a reaction medium to mitigate production of
      polycyclic aromatic hydrocarbons from the thermal decomposition of styrene
      butadiene rubber.
AB  - The CO(2) cofeed impact on the pyrolysis of styrene butadiene rubber (SBR) was
      investigated using thermogravimetric analysis (TGA) coupled to online gas
      chromatography/mass spectroscopy (GC/MS). The direct comparison of the chemical
      species evolved from the thermal degradation of SBR in N(2) and CO(2) led to a
      preliminary mechanistic understanding of the formation and relationship of light
      hydrocarbons (C(1-4)), aromatic derivatives, and polycyclic aromatic hydrocarbons
      (PAHs), clarifying the role of CO(2) in the thermal degradation of SBR. The
      identification and quantification of over 50 major and minor chemical species
      from hydrogen and benzo[ghi]perylene were carried out experimentally in the
      temperature regime between 300 and 500  degrees C in N(2) and CO(2). The
      significant amounts of benzene derivatives from the direct bond dissociation of
      the backbone of SBR, induced by thermal degradation, provided favorable
      conditions for PAHs by the gas-phase addition reaction at a relatively low
      temperature compared to that with conventional fuels such as coal and petroleum
      derived fuels. However, the formation of PAHs in a CO(2) atmosphere was decreased
      considerably (i.e., ~50%) by the enhanced thermal cracking behavior, and the
      ultimate fates of these species were determined by different pathways in CO(2)
      and N(2) atmospheres. Consequently, this work has provided a new approach to
      mitigate PAHs by utilizing CO(2) as a reaction medium in thermochemical
      processes.

PMID- 22950721
TI  - Polymorphic infection and organogenesis patterns induced by a Rhizobium
      leguminosarum isolate from Lotus root nodules are determined by the host
      genotype.
AB  - To sample the natural variation in genes controlling compatibility in the legume
      rhizobium symbiosis, we isolated rhizobia from nodules of endemic Lotus species
      from 21 sites across Europe. The majority of isolates were identified as
      Mesorhizobium- or Bradyrhizobium-related and formed nitrogen-fixing root nodules
      on Lotus corniculatus and L. pendunculatus, respectively, thus confirming
      previously defined cross-inoculation groups. Rhizobium leguminosarum (Rl) strain
      Norway, isolated from L. corniculatus nodules, displayed an exceptional
      phenotypic variation on different Lotus genotypes. On L. burttii, Rl Norway
      formed infected nodules, whereas tumors and elongated infected swellings were
      induced on L. glaber and L. japonicus ecotype Nepal, respectively. A symbiosis-
      and Nod-factor-responsive promoter:uidA fusion was strongly and rapidly induced
      in L. japonicus Gifu, but infection threads or signs of nodule organogenesis were
      absent. This complex phenotypic pattern was not mimicked by either of three
      engineered R. leguminosarum bv viciae strains producing different Nod-factor
      variants. Intriguingly, Rl Norway formed infection threads on Pisum sativum cv
      Sparkle, but failed to induce organogenesis. Rl Norway thus uncovered variation
      in symbiotic capabilities among diploid Lotus species and ecotypes that are
      obscured by optimally adapted M. loti strains. These contrasting infection and
      organogenesis phenotypes reveal recent diversification of recognition
      determinants in Lotus.

PMID- 22950722
TI  - New approaches for bottom-up assembly of tobacco mosaic virus-derived
      nucleoprotein tubes on defined patterns on silica- and polymer-based substrates.
AB  - The capability of some natural molecular building blocks to self-organize into
      defined supramolecular architectures is a versatile tool for nanotechnological
      applications. Their site-selective integration into a technical context, however,
      still poses a major challenge. RNA-directed self-assembly of tobacco mosaic virus
      derived coat protein on immobilized RNA scaffolds presents a possibility to grow
      nucleoprotein nanotubes in place. Two new methods for their site-selective,
      bottom-up assembly are introduced. For this purpose, isothiocyanate alkoxysilane
      was used to activate oxidic surfaces for the covalent immobilization of DNA
      oligomers, which served as linkers for assembly-directing RNA. Patterned
      silanization of surfaces was achieved (1) on oxidic surfaces via dip-pen
      nanolithography and (2) on polymer surfaces (poly(dimethylsiloxane)) via
      selective oxidization by UV-light irradiation in air. Atomic force microscopy and
      X-ray photoelectron spectroscopy were used to characterize the surfaces. It is
      shown for the first time that the combination of the mentioned structuring
      methods and the isothiocyanate-based chemistry is appropriate (1) for the site
      selective immobilization of nucleic acids and, thus, (2) for the formation of
      viral nanoparticles by bottom-up self-assembly after adding the corresponding
      coat proteins.

PMID- 22950724
TI  - Fanning the flame of prevention effort.

PMID- 22950723
TI  - Unusual death due to a bleeding from a varicose vein: a case report.
AB  - BACKGROUND: Varicose veins are a common entity presenting a worldwide
      distribution. Although they are usually benign, sometimes are proved to be a
      threatening condition. Massive hemorrhage is an unusual complication of this
      common venous pathology that demands immediate medical intervention. CASE
      PRESENTATION: We present a case of a 66-year-old woman found dead in her house
      surrounded by a large quantity of blood. Autopsy revealed a 7 mm ulcer on the
      internal surface of the left lower leg communicating with a varicose vein, signs
      of exsanguinations and liver cirrhosis. Toxicological analysis was negative.
      CONCLUSION: Massive hemorrhage from a ruptured varicosity is a severe medical
      emergency. Awareness of the risk of massive hemorrhage may provoke preventive
      treatment to be undertaken so as terminal loss of consciousness and a subsequent
      unattended death to be averted.

PMID- 22950725
TI  - Virtual reality training followed by box training improves the laparoscopic
      skills of novice surgeons.
AB  - BACKGROUND: The detailed influence of virtual reality training (VRT) and box
      training (BT) on laparoscopic performance is unknown; we aimed to determine the
      optimal order of imparting these training programs. MATERIAL AND METHODS: This
      randomized controlled trial involved two groups, each with 20 participants
      without prior laparoscopic surgical experience: A BT-VRT group (60 min BT
      followed by 60 min VRT) and a VRT-BT group (60 min VRT followed by 60 min BT). We
      objectively assessed the laparoscopic skills with a motion-analysis system
      (Hiroshima University Endoscopic Surgical Assessment Device: HUESAD), which
      reliably assesses surgical dexterity. Skill assessment was performed before and
      after the training session. RESULTS: No inter-group differences were identified
      in the study measures at the pre-training assessment. In both groups, the
      performance on all tasks was significantly better at the post-training assessment
      than at the pre-training assessment. However, the outcome of the tests using the
      HUESAD was significantly better in the VRT-BT group than in the BT-VRT group at
      the post-training assessment. CONCLUSIONS: VRT followed by BT effectively
      improves the dexterity of novice surgeons during initial laparoscopic
      (combination) training.

PMID- 22950726
TI  - Catching up with the digital evolution.

PMID- 22950727
TI  - The excesses of care: a matter of understanding the asymmetry of power.
AB  - The aim of the article is to illustrate concrete problems in the asymmetrical
      nurse-patient power relationship. It is an ethical demand that the nurse is faced
      with the challenges that the power in the relation is administered so that the
      patient's room for action is expanded and trust maintained. It is an essential
      message in care philosophy, but in clinical practice, success is not always
      achievable. A hidden and more or less unconscious restriction of the patient's
      room for action may result in the excesses of care. Three selected aspects:
      dependence, trust, and power described by the Danish philosopher K.E. Logstrup
      and the Norwegian nursing philosopher Kari Martinsen's care philosophy has
      inspired this empirically based examination of some current barriers in the
      asymmetrical nurse-patient relationship. On the basis of qualitative interviews
      with six patients and six nurses, the research thus provides an identifying and
      problem-exploratory examination of some current obstacles in which the handling
      of trust and power reflects the excesses of care. The findings develop three
      themes. 'Being a burden' acknowledges that the balance of power will always tip
      to the nurse's advantage. The second theme, 'Doing only what's absolutely
      necessary', shows how a fixation with 'technicalism' creates a distance between
      people that may constrain the patient's room for action. The last theme is
      concerning the nurse's ability to navigate between closeness and distance is
      essential in avoiding 'the excesses of care', paternalism, and
      overprotectiveness. A situation in which distance takes the upper hand and care
      turns into paternalism. A different situation would arise if the nurse's emotions
      became sentimental or intimate with the result that closeness gets the upper
      hand. To avoid a harmful exercise of power and the excesses of care, the findings
      have demonstrated that a relationship-based caring is a demand for situation
      specific sensitive attention skills.

PMID- 22950728
TI  - Abductive reasoning and qualitative research.
AB  - Abduction, deduction and induction describe forms of reasoning. Deduction and
      induction are discussed in the nursing literature. However, abduction has been
      largely neglected by nurse scholars. In this paper it is proposed that abduction
      may play a part in qualitative data analysis - specifically, in the
      identification of themes, codes, and categories. Abduction is not, in research,
      restricted to or associated with any particular methodology. Nevertheless,
      situating abduction in qualitative research facilitates the identification of
      three interlinked issues. First, it is suggested that abductively derived claims
      require support from deductive and inductively sourced evidence if they are to
      'hold' and, yet, in qualitative research this is clearly problematic. Second,
      difficulties in choosing between alternative plausible hypotheses (i.e.
      concerning theme, code, and category description) are explored through an
      examination of the 'generality problem'. Third, the role of background and
      auxiliary theories in adjudicating between hypothesis options is discussed. It is
      argued that if qualitative researchers utilize abductive inference in the manner
      suggested, then the peculiarly fallible nature of abduction must be acknowledged
      and, in consequence, the action guiding potential of qualitative research
      findings is compromised.

PMID- 22950729
TI  - Only a whisper away. A philosophical view of the awake patient's situation during
      regional anaesthetics and surgery.
AB  - In this study the awake patient's intraoperative situation and experiences during
      regional anaesthetics and surgery are reflected upon by using the work of the
      French philosopher Maurice Merleau-Ponty. Merleau-Ponty's phenomenological idea
      of the body as being at the centre of the world highlights the patient's embodied
      position and bestows significance onto the body as a whole, as a lived body. A
      case, based on the findings from a previous interview study, is presented as a
      contextual starting point where a patient goes from having a familiar body
      recognized as her own to having a partially anaesthetized body experienced as an
      unknown object. The intraoperative caring space is described in this context as
      the mutual ground where the awake patient and the nurse anaesthetist (NA) can
      interact to create meaning. The NA can act as the patient's bodily extension to
      bridge the gap between the patient's experiences and the situation. This calls
      for the NA's proximity and genuine presence in order to meet and understand the
      patient's awake experiences. Learning from the patient's situatedness gives
      information that is valuable for NAs to share with patients who are less
      experienced with this contextual situation. The challenge for the NA is not to
      perform routine-based care, but to acknowledge every patient's lifeworld and
      uniqueness thus enabling the patient to move easily along the mind-body-world
      continuum. The core of intraoperative care is to provide support and promote well
      being of awake patients in the intraoperative environment. The use of a
      philosophical perspective is relevant for nurses who work in an intraoperative
      setting where patients undergo regional anaesthetics. This study shows how
      nursing research using phenomenological philosophy can help uncover new meanings
      known only to the patients living the experience.

PMID- 22950730
TI  - Furthering the sceptical case against virtue ethics in nursing ethics.
AB  - In a recent article in this journal I presented a sceptical argument about the
      current prominence of virtue ethics in nursing ethics. Daniel Putman has
      responded with a defence of the relevance of virtue in nursing. The present
      article continues this discussion by clarifying, defending, and expanding the
      sceptical argument. I start by emphasizing some features of the sceptical case,
      including assumptions about the nature of sceptical arguments, and about the
      character of both virtue ethics and nursing ethics. Then I respond to objections
      of Putman's such as that, according to virtue ethics, virtue is relevant to the
      whole of a human life, including one's behaviour in a professional context; and
      that eudaimonia should be central in explaining and motivating a nurse's decision
      to enter the profession. Having argued that these objections are not compelling,
      I go on to discuss an interesting recent attempt to reassert the role of virtue
      ethics in the ethics of professions, including nursing. This centres on whether
      role-specific obligations - e.g. the obligations that arise for a moral agent qua
      lawyer or mother - can be accommodated in a virtue ethics approach. Sean Cordell
      has argued that the difficulty of accommodating role-specific obligations results
      in an 'institution-shaped gap' in virtue ethics. He suggests a way of meeting
      this difficulty that appeals to the ergon of institutions. I endorse the negative
      point that role-specific obligations elude virtue ethics, but argue that the
      appeal to the ergon of institutions is unsuccessful. The upshot is further
      support for scepticism about the virtue ethics approach to nursing ethics. I end
      by gesturing to some of the advantages of a sceptical view of virtue ethics in
      nursing ethics.

PMID- 22950731
TI  - A cyborg ontology in health care: traversing into the liminal space between
      technology and person-centred practice.
AB  - Person-centred practice indubitably seems to be the antithesis of technology. The
      ostensible polarity of technology and person-centred practice is an easy road to
      travel down and in their various forms has been probably travelled for decades if
      not centuries. By forging ahead or enduring these dualisms, we continue to
      approach and recede, but never encounter the elusive and the liminal space
      between technology and person-centred practice. Inspired by Haraway's work, we
      argue that healthcare practitioners who critically consider their cyborg ontology
      may begin the process to initiate and complicate the liminal and sought after
      space between technology and person-centred practice. In this paper, we draw upon
      Haraway's idea that we are all materially and ontologically cyborgs. Cyborgs, the
      hybridity of machine and human, are part of our social reality and embedded in
      our everyday existence. By considering our cyborg ontology, we suggest that
      person-centred practice can be actualized in the contextualized, embodied and
      relational spaces of technology. It is not a question of espousing technology or
      person-centred practice. Such dualisms have been historically produced and
      reproduced over many decades and prevented us from recognizing our own cyborg
      ontology. Rather, it is salient that we take notice of our own cyborg ontology
      and how technological, habitual ways of being may prevent (and facilitate) us to
      recognize the embodied and contextualized experiences of patients. A disruption
      and engagement with the habitual can ensure we are not governed by technology in
      our logics and practices of care and can move us to a conscious and critical
      integration of person-centred practice in the technologized care environments. By
      acknowledging ourselves as cyborgs, we can recapture and preserve our humanness
      as caregivers, as well as thrive as we proceed in our technological way of being.

PMID- 22950732
TI  - Phenomenology, ethics, and the crisis of the lived-body.

PMID- 22950733
TI  - The organ donation process: a humanist perspective based on the experience of
      nursing care.

PMID- 22950735
TI  - An archaeal protein evolutionarily conserved in prokaryotes is a zinc-dependent
      metalloprotease.
AB  - A putative protease gene (tldD) was previously identified from studying tolerance
      of letD encoding the CcdB toxin of a toxin-antidote system of the F plasmid in
      Escherichia coli. While this gene is evolutionarily conserved in archaea and
      bacteria, the proteolytic activity of encoded proteins remained to be
      demonstrated experimentally. Here we studied Sso0660, an archaeal TldD homologue
      encoded in Sulfolobus solfataricus by overexpression of the recombinant protein
      and characterization of the purified enzyme. We found that the enzyme is active
      in degrading azocasein and FITC-BSA substrates. Protease inhibitor studies showed
      that EDTA and o-phenanthroline, two well-known metalloprotease inhibitors, either
      abolished completely or strongly inhibited the enzyme activity, and flame
      spectrometric analysis showed that a zinc ion is a cofactor of the protease.
      Furthermore, the protein forms disulfide bond via the Cys416 residue, yielding
      protein dimer that is the active form of the enzyme. These results establish for
      the first time that tidD genes encode zinc-containing proteases, classifying them
      as a family in the metalloprotease class.

PMID- 22950736
TI  - A mechanistic basis for amplification differences between samples and between
      genome regions.
AB  - BACKGROUND: For many analytical methods the efficiency of DNA amplification
      varies across the genome and between samples. The most affected genome regions
      tend to correlate with high C + G content, however this relationship is complex
      and does not explain why the direction and magnitude of effects varies
      considerably between samples. RESULTS: Here, we provide evidence that sequence
      elements that are particularly high in C + G content can remain annealed even
      when aggressive melting conditions are applied. In turn, this behavior creates
      broader 'Thermodynamically Ultra-Fastened' (TUF) regions characterized by
      incomplete denaturation of the two DNA strands, so reducing amplification
      efficiency throughout these domains. CONCLUSIONS: This model provides a
      mechanistic explanation for why some genome regions are particularly difficult to
      amplify and assay in many procedures, and importantly it also explains inter
      sample variability of this behavior. That is, DNA samples of varying quality will
      carry more or fewer nicks and breaks, and hence their intact TUF regions will
      have different lengths and so be differentially affected by this amplification
      suppression mechanism - with 'higher' quality DNAs being the most vulnerable. A
      major practical consequence of this is that inter-region and inter-sample
      variability can be largely overcome by employing routine fragmentation methods
      (e.g. sonication or restriction enzyme digestion) prior to sample amplification.

PMID- 22950737
TI  - Soil suppressiveness to fusarium disease: shifts in root microbiome associated
      with reduction of pathogen root colonization.
AB  - Soil suppressiveness to Fusarium disease was induced by incubating sandy soil
      with debris of wild rocket (WR; Diplotaxis tenuifolia) under field conditions. We
      studied microbial dynamics in the roots of cucumber seedlings following
      transplantation into WR-amended or nonamended soil, as influenced by inoculation
      with Fusarium oxysporum f. sp. radicis-cucumerinum. Disease symptoms initiated in
      nonamended soil 6 days after inoculation, compared with 14 days in WR-amended
      soil. Root infection by F. oxysporum f. sp. radicis-cucumerinum was quantified
      using real-time polymerase chain reaction (PCR). Target numbers were similar 3
      days after inoculation for both WR-amended and nonamended soils, and were
      significantly lower (66%) 6 days after inoculation and transplanting into the
      suppressive (WR-amended) soil. This decrease in root colonization was correlated
      with a reduction in disease (60%) 21 days after inoculation and transplanting
      into the suppressive soil. Fungal community composition on cucumber roots was
      assessed using mass sequencing of fungal internal transcribed spacer gene
      fragments. Sequences related to F. oxysporum, Fusarium sp. 14005, Chaetomium sp.
      15003, and an unclassified Ascomycota composed 96% of the total fungal sequences
      in all samples. The relative abundances of these major groups were highly
      affected by root inoculation with F. oxysporum f. sp. radicis-cucumerinum, with a
      10-fold increase in F. oxysporum sequences, but were not affected by the WR
      amendment. Quantitative analysis and mass-sequencing methods indicated a
      qualitative shift in the root's bacterial community composition in suppressive
      soil, rather than a change in bacterial numbers. A sharp reduction in the size
      and root dominance of the Massilia population in suppressive soil was accompanied
      by a significant increase in the relative abundance of specific populations;
      namely, Rhizobium, Bacillus, Paenibacillus, and Streptomyces spp. Composition of
      the Streptomyces community shifted significantly, as determined by PCR denaturing
      gradient gel electrophoresis, resulting in an increase in the dominance of a
      specific population in suppressive soils after only 3 days. This shift was
      related mainly to the increase in Streptomyces humidus, a group previously
      described as antagonistic to phytopathogenic fungi. Thus, suitable soil amendment
      resulted in a shift in the root's bacterial communities, and infection by a
      virulent pathogen was contained by the root microbiome, leading to a reduced
      disease rate.

PMID- 22950738
TI  - Production and release of asexual sporangia in Plasmopara viticola.
AB  - To study the influence of environmental conditions on sporulation of Plasmopara
      viticola lesions under vineyard's conditions, unsprayed vines were inspected
      every second or third day and the numbers of sporulating and nonsporulating
      lesions were counted in two North Italy vineyards in 2008 to 2010. Infected
      leaves were removed so that only fresh lesions were assessed at each field
      assessment. Sporulation was studied at two scales, across field assessments and
      across the seasonal population of lesions. Frequencies of sporulating lesions
      were positively correlated with the numbers of moist hours in the preceding dark
      period (i.e., the number of hours between 8:00 p.m. and 7:00 a.m. with relative
      humidity >=80%, rainfall >0 mm, or wetness duration >30 min). In a receiver
      operating characteristic analysis, predicted sporulation based on the occurrence
      of >=3 moist hours at night provided overall accuracy of 0.85. To study the time
      course of sporulation on lesions which were not washed by rainfall, numbers of
      sporangia produced per square millimeter of lesion were estimated on individual
      cohorts of lesions over the whole infectious period. The numbers of sporangia per
      square millimeter of lesion increased rapidly during the first 4 days after the
      beginning of sporulation and then tapered off prior to a halt; the time course of
      cumulative sporangia production by a lesion followed a monomolecular growth model
      (R(2) = 0.97). The total number of sporangia produced by a square millimeter of
      lesion increased as the maximum temperature decreased and moist hours in the dark
      increased. To study the release pattern of the sporangia, spore samplers were
      placed near grapevines with sporulating lesions. Airborne sporangia were caught
      in 91.2% of the days over a wide range of weather conditions, including rainless
      periods. The results of this study provide quantitative information on production
      of P. viticola sporangia that may help refine epidemiological models used as
      decision aids in grape disease management programs.

PMID- 22950739
TI  - Online nanoscale ERLIC-MS outperforms RPLC-MS for shotgun proteomics in complex
      mixtures.
AB  - We have explored the use of electrostatic repulsion hydrophilic interaction
      chromatography (ERLIC) as an alternative to the gold-standard in shotgun
      proteomics: reversed-phase (RP) LC for online ESI-MS/MS. Conditions for sample
      solubilization and initial gradient conditions were optimized to strike a balance
      between peptide solubility and maximum peptide retention when using mobile phase
      with high organic solvent concentration. Online ERLIC-MS demonstrated a 57%
      increase in total peptide identifications compared to RP-MS. We examined the
      mechanism of this improved performance and found that it stems from ERLIC's
      propensity to retain longer peptides, which can be identified with greater
      confidence. Online nanoscale ERLIC-MS provides a powerful new tool for enhancing
      MS-based shotgun proteomic in a broad range of applications.

PMID- 22950740
TI  - Origin of low sensitizing efficiency of quantum dots in organic solar cells.
AB  - Organic semiconductors are of great interest for application in cheap and
      flexible solar cells. They have a typical absorption onset in the visible.
      Infrared light can be harvested by use of lead-chalcogenide quantum dot
      sensitizers. However, bulk-heterojunction solar cells with quantum-dot
      sensitizers are inefficient. Here we use ultrafast transient absorption and time
      domain terahertz spectroscopy to show that charge localization on the quantum dot
      leads to enhanced coulomb attraction of its counter charge in the organic
      semiconductor. This localization-enhanced coulomb attraction is the fundamental
      cause of the poor efficiency of these photovoltaic architectures. It is of prime
      importance for improving solar cell efficiency to directly photogenerate
      spatially separated charges. This can be achieved when both charges are
      delocalized. Our findings provide a rationalization in the development of
      photovoltaic architectures that exploit quantum dots to harvest the near-infrared
      part of the solar spectrum more efficiently.

PMID- 22950741
TI  - Photopolymeric multifunctional dendrimer toward holographic applications.
AB  - We present a photopolymeric multifunctional dendrimer for holographic
      applications. In this study, we described a synthesis of multiphotoreactive
      dendrimer and phase compatible polymer matrix as well as a numerical simulation
      of the dendrimer. This holographic photopolymer containing a nanosized
      photoreactive organic dendrimer could address the aggregation issue of
      conventional inorganic nanoparticle additives and allowed writing-induced
      shrinkage to be successfully reduced to the extent of acceptable values for 130
      MUm thick film. In this report, holographic performance including diffraction
      efficiency (DE), transmission, photosensitivity, modulation of refractive index,
      polarization sensitivity, and volume shrinkage has been discussed. The page-wise
      recording by using an amplitude spatial light modulator (SLM) was also
      demonstrated.

PMID- 22950742
TI  - Nanotechnology based platforms for survivin targeted drug discovery.
AB  - INTRODUCTION: Development of an effective, safe and targeted drug delivery system
      to fight cancer and other diseases is a prime focus in the area of drug
      discovery. The emerging field of nanotechnology has revolutionised the way cancer
      therapy and diagnosis is achieved primarily due to the recent advances in
      material engineering and drug availability. Further, the recognition of the
      crucial role played by anti-apoptotic proteins such as survivin, has initiated
      the development of therapeutics that can target this protein as an attempt to
      develop alternative cancer therapies. However, a key challenge faced in drug
      development is the efficient delivery of survivin-targeted molecules to specific
      areas in the body. AREAS COVERED: This review primarily focuses on the different
      strategies employing nanotechnology for targeting survivin expressed in human
      cancers. Different nanomaterials incorporating nucleic molecules or drugs
      targeted at survivin are discussed and the results obtained from studies are
      highlighted. EXPERT OPINION: There are extensive studies reporting different
      treatment regimens for cancer, however, they still result in systemic toxicity,
      reduced bioavailability and ineffective delivery. Novel approaches involve the
      use of biocompatible nanomaterials together with gene or drug molecules to target
      proteins such as survivin, which is overexpressed in cancerous cells. These
      nanoformulations allow the benefits of protecting easily degradable molecules,
      allow controlled release, and enhance targeted delivery and effectiveness. Hence,
      nanotherapy utilizing survivin targeting can be considered to play a key role in
      the development of personalized nanomedicine for cancer.

PMID- 22950743
TI  - Antioxidant capacity of teas and herbal infusions: polarographic assessment.
AB  - Hydrogen peroxide scavenging (HPS) activity of unfermented (green, yellow, and
      white), partially fermented (oolong), and completely fermented (black) tea (
      Camellia sinensis ), mate ( Ilex paraguariensis ), and various herbal infusions,
      as well as individual compounds (flavan-3-ols, flavonols, cinnamic and benzoic
      acids, and methylxanthines), was assessed by recently developed direct current
      (DC) polarographic assay. Correlations of tea and herbal infusion HPS activity
      with total phenolic content determined using the Folin-Ciocalteu assay (FC-GAE)
      (0.81 and 0.93), ferric reducing/antioxidant power (FRAP) (0.97 and 0.92), 1,1
      diphenyl-2-picrylhydrazyl (DPPH) (0.77 and 0.80), and 2,2'-azinobis(3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging (0.86 and 0.86) were
      statistically significant. Correlations between relative antioxidant capacity
      index (RACI), calculated by assigning all applied assays equal weight, and HPS
      (0.98), FRAP (0.97), ABTS (0.89), and DPPH (0.89) confirmed DC polarographic
      assay reliability when applied individually. Correlation analysis, ANOVA, and
      Levene and Tukey's HSD tests unequivocally confirmed this reliable, rapid, and
      low-cost assay validity, clearly demonstrating its advantages over
      spectrophotometric assays applied.

PMID- 22950744
TI  - Pre-test of questions on health-related resource use and expenditure, using
      behaviour coding and cognitive interviewing techniques.
AB  - BACKGROUND: Validated instruments collecting data on health-related resource use
      are lacking, but required, for example, to investigate predictors of healthcare
      use or for health economic evaluation.The objective of the study was to develop,
      test and refine a questionnaire collecting data on health-related resource use
      and expenditure in patients with diabetes. METHODS: The questionnaire was tested
      in 43 patients with diabetes mellitus types 1 and 2 in Germany. Response
      behaviour suggestive of problems with questions (item non-response, request for
      clarification, comments, inadequate answer, "don't know") was systematically
      registered. Cognitive interviews focusing on information retrieval and
      comprehension problems were carried out. RESULTS: Many participants had
      difficulties answering questions pertaining to frequency of visits to the general
      practitioner (26%), time spent receiving healthcare services (39%), regular
      medication currently taken (35%) and out of pocket expenditure on medication
      (42%). These difficulties seem to result mainly from poor memory. A number of
      comprehension problems were established and relevant questions were revised
      accordingly. CONCLUSION: The questionnaire on health-related resource use and
      expenditure for use in diabetes research in Germany was developed and refined
      after careful testing. Ideally, the questionnaire should be externally validated
      for different modes of administration and recall periods within a variety of
      populations.

PMID- 22950745
TI  - Whole genome methylation profiles as independent markers of survival in stage
      IIIC melanoma patients.
AB  - BACKGROUND: The clinical course of cutaneous melanoma (CM) can differ
      significantly for patients with identical stages of disease, defined clinico
      pathologically, and no molecular markers differentiate patients with such a
      diverse prognosis. This study aimed to define the prognostic value of whole
      genome DNA methylation profiles in stage III CM. METHODS: Genome-wide methylation
      profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in
      short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised
      K-means partitioning clustering was exploited to sort patients into 2 groups
      based on their methylation profiles. Methylation patterns related to the
      discovered groups were determined using the nearest shrunken centroid
      classification algorithm. The impact of genome-wide methylation patterns on
      overall survival (OS) was assessed using Cox regression and Kaplan-Meier
      analyses. RESULTS: Unsupervised K-means partitioning by whole genome methylation
      profiles identified classes with significantly different OS in stage IIIC CM
      patients. Patients with a "favorable" methylation profile had increased OS (P =
      0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC
      patients with a "favorable" vs. "unfavorable" methylation profile were 31.5 and
      10.4 months, respectively. The 5 year OS for stage IIIC patients with a
      "favorable" methylation profile was 41.2% as compared to 0% for patients with an
      "unfavorable" methylation profile. Among the variables examined by multivariate
      Cox regression analysis, classification defined by methylation profile was the
      only predictor of OS (Hazard Ratio = 2.41, for "unfavorable" methylation profile;
      95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature
      able to correctly assign prognosis (overall error rate = 0) in stage IIIC
      patients on the basis of distinct methylation-defined groups was also identified.
      CONCLUSIONS: A discrete whole-genome methylation signature has been identified as
      molecular marker of prognosis for stage IIIC CM patients. Its use in daily
      practice is foreseeable, and promises to refine the comprehensive clinical
      management of stage III CM patients.

PMID- 22950746
TI  - Weed host specificity of the aphid, Aphis spiraecola: developmental and
      reproductive performance of aphids in relation to plant growth and leaf chemicals
      of the Siam weed, Chromolaena odorata.
AB  - Density, distribution, and nutritional quality of plants are the causal basis of
      host plant selection in aphids. Nutritional qualities of a plant vary according
      to its growth stage and also in response to seasonal variation. How host plant
      growth stages shape aphid performance was studied in Aphis spiraecola Patch
      (Homoptera: Aphididae) on the perennial Siam weed, Chromolaena odorata (L.) King
      and Robinson (Asterales: Asteraceae). This plant species is the preferred host in
      the hot and humid tropical parts of northeast and southern India. Variations in
      developmental and reproductive performances in apterous viviparous female aphids
      were recorded in relation to differences in leaf chemicals in different growth
      stages of C. odorata. Aphids reproduced at higher rates in the vegetative stage
      of C. odorata when developmental time was shortest, and fecundity was higher in a
      longer reproductive time. Intrinsic rate of increase and net reproductive rate
      were also recorded to be higher in the vegetative stage of the weed host. In the
      vegetative stage, leaves contained higher quantity of proteins and nitrogen,
      which are vital for insect reproduction. Results of this study have demonstrated
      that A spiraecola showed synchronization of its developmental and reproductive
      performances to growth stages of C. odorata, which occur in high abundance in the
      study area.

PMID- 22950747
TI  - Introduction to the special issue honoring Professor David R. Bickers.

PMID- 22950748
TI  - Phylogenetic diversity of actinomycetes cultured from coastal multipond solar
      saltern in Tuticorin, India.
AB  - BACKGROUND: Hypersaline solar salterns are extreme environments in many tropical
      and subtropical regions throughout the world. In India, there are several coastal
      solar salterns along with the coastal line of the Bay of Bengal and Arabian Sea
      and inland solar salterns around Sambhar saltlake, from which sodium chloride is
      obtained for human consumption and industrial needs. Studies on characterization
      of such coastal and inland solar salterns are scarce and both the bacterial and
      archaeal diversity of these extreme saline environment remains poorly understood.
      Moreover, there are no reports on exclusive diversity of actinomycetes inhabiting
      Indian solar salterns. RESULTS: Soil sediments were collected from both
      concentrator and crystallizer ponds of solar salterns and subjected to detailed
      physico-chemical analysis. Actinomycetes were selectively isolated by employing
      selective processing methods and agar media. A total of 12 representatives were
      selected from the 69 actinomycete isolates obtained from the saltern soil
      samples, using Amplified Ribosomal DNA Restriction Analysis. Sequencing and
      analysis of 16S rDNA from chosen representative isolates displayed the presence
      of members affiliated to actinobacterial genera: Streptomyces, Micromonospora,
      Nocardia, Nocardiopsis, Saccharopolyspora and Nonomuraea. The genus Streptomyces
      was found to be the dominant among the isolates. Furthermore, rare actinomycete
      genus Nonomuraea was isolated for the first time from Indian solar salterns.
      CONCLUSIONS: To the best of our knowledge, this study constitutes the first
      characterization of actinomycete diversity centred on solar salterns located in
      the eastern coastal region of India. Furthermore, this is the very first report
      of isolation of Nonomuraea species from solar salterns and also from India. As
      actinomycetes encompass recurrently foremost sources of biotechnologically
      important member of the microbial communities, the actinomycetes retrieved from
      the Indian saltern soil samples laid the platform to search for novel
      biotechnologically significant bioactive substances.

PMID- 22950749
TI  - Determinants of periodontal health in pregnant women and association with
      infants' anthropometric status: a prospective cohort study from Eastern Uganda.
AB  - BACKGROUND: Preterm-low birth weight delivery is a major cause of infant
      morbidity and mortality in sub Saharan Africa and has been linked to poor
      periodontal health during pregnancy. This study investigated predisposing and
      enabling factors as Determinants of oral health indicators in pregnancy as well
      as the association between periodontal problems at 7 months gestational age and
      the infants' anthropometric status. METHOD: A community -based prospective cohort
      study was conducted in Mbale, Eastern Uganda between 2006 and 2008. Upon
      recruitment, 713 pregnant women completed interviews and a full mouth oral
      clinical examination using the CPITN (Community Periodontal Index of Treatment
      Need) and OHI-S (Simplified Oral Hygiene) indices. A total of 593 women were
      followed up with anthropometric assessments of their infants 3 weeks after
      delivery. Multiple logistic regression analyses were used to identify independent
      determinants of periodontal problems and use of dental services during pregnancy.
      Analysis of covariance (ANCOVA) was used to investigate the relationship between
      periodontal problems and the child's anthropometric status in terms of wasting,
      underweight and stunting. RESULTS: A total of 67.0% women presented with
      periodontal problems, 12.1% with poor oral hygiene, 29.8% with recent dental
      visit and 65.0% with periodontal symptoms. Of the infants, 2.0% were wasted, 6.9%
      were underweight and 10.0% were stunted. The odds ratio of having CPI > 0
      increased with increased maternal age and single marital status, and was lower in
      primiparous women and those who used mosquito bed nets. Mean wasting scores
      discriminated between mothers with CPI = 0 and CPI > 0 as well as between mothers
      with good and poor OHI-S scores. CONCLUSIONS: Socio-demographic factors and
      information about oral health were associated with oral health indicators in
      pregnant women. Second, the height- for- age status at 3 weeks postpartum was
      worse in infants of mothers having periodontal problems and poor oral hygiene
      during pregnancy. Efforts to prevent oral diseases during pregnancy should be
      part of the local state and national health policy agenda in Uganda.

PMID- 22950750
TI  - Effect of dissolved CO2 on a shallow groundwater system: a controlled release
      field experiment.
AB  - Capturing carbon dioxide (CO(2)) emissions from industrial sources and injecting
      the emissions deep underground in geologic formations is one method being
      considered to control CO(2) concentrations in the atmosphere. Sequestering CO(2)
      underground has its own set of environmental risks, including the potential
      migration of CO(2) out of the storage reservoir and resulting acidification and
      release of trace constituents in shallow groundwater. A field study involving the
      controlled release of groundwater containing dissolved CO(2) was initiated to
      investigate potential groundwater impacts. Dissolution of CO(2) in the
      groundwater resulted in a sustained and easily detected decrease of ~3 pH units.
      Several trace constituents, including As and Pb, remained below their respective
      detections limits and/or at background levels. Other constituents (Ba, Ca, Cr,
      Sr, Mg, Mn, and Fe) displayed a pulse response, consisting of an initial increase
      in concentration followed by either a return to background levels or slightly
      greater than background. This suggests a fast-release mechanism (desorption,
      exchange, and/or fast dissolution of small finite amounts of metals) concomitant
      in some cases with a slower release potentially involving different solid phases
      or mechanisms. Inorganic constituents regulated by the U.S. Environmental
      Protection Agency remained below their respective maximum contaminant levels
      throughout the experiment.

PMID- 22950751
TI  - Establishing a health demographic surveillance site in Bhaktapur district, Nepal:
      initial experiences and findings.
AB  - BACKGROUND: A health demographic surveillance system (HDSS) provides longitudinal
      data regarding health and demography in countries with coverage error and poor
      quality data on vital registration systems due to lack of public awareness,
      inadequate legal basis and limited use of data in health planning. The health
      system in Nepal, a low-income country, does not focus primarily on health
      registration, and does not conduct regular health data collection. This study
      aimed to initiate and establish the first HDSS in Nepal. RESULTS: We conducted a
      baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The
      study surveyed 2,712 households comprising a total population of 13,669. The sex
      ratio in the study area was 101 males per 100 females and the average household
      size was 5. The crude birth and death rates were 9.7 and 3.9/1,000
      population/year, respectively. About 11% of births occurred at home, and we found
      no mortality in infants and children less than 5 years of age. Various health
      problems were found commonly and some of them include respiratory problems
      (41.9%); headache, vertigo and dizziness (16.7%); bone and joint pain (14.4%);
      gastrointestinal problems (13.9%); heart disease, including hypertension (8.8%);
      accidents and injuries (2.9%); and diabetes mellitus (2.6%). The prevalence of
      non-communicable disease (NCD) was 4.3% (95% CI: 3.83; 4.86) among individuals
      older than 30 years. Age-adjusted odds ratios showed that risk factors, such as
      sex, ethnic group, occupation and education, associated with NCD. CONCLUSION: Our
      baseline survey demonstrated that it is possible to collect accurate and reliable
      data in a village setting in Nepal, and this study successfully established an
      HDSS site. We determined that both maternal and child health are better in the
      surveillance site compared to the entire country. Risk factors associated with
      NCDs dominated morbidity and mortality patterns.

PMID- 22950752
TI  - Friction-mediated dynamic disordering of phospholipid membrane by mechanical
      motions of photoresponsive molecular glue: activation of ion permeation.
AB  - A water-soluble photoresponsive molecular glue, Azo-(18)Glue, consisting of a
      photochromic azobenzene core and two adhesive dendritic wedges with a total of 18
      peripheral guanidinium ion (Gu(+)) pendants tightly adheres to the surface of a
      phospholipid membrane, even in buffer, via a multivalent salt-bridge formation
      with phosphate anions. A photomechanical motion of adhering Azo-(18)Glue possibly
      gives rise to dynamic structural disordering of the phospholipid membrane and
      activates transmembrane ion permeation. In sharp contrast, no activation of ion
      permeation results when poorly adhesive Azo-(6)Glue carrying only six Gu(+)
      pendants is used in place of Azo-(18)Glue.

PMID- 22950753
TI  - Necrotrophic pathogens use the salicylic acid signaling pathway to promote
      disease development in tomato.
AB  - Plants use different immune pathways to combat pathogens. The activation of the
      jasmonic acid (JA)-signaling pathway is required for resistance against
      necrotrophic pathogens; however, to combat biotrophic pathogens, the plants
      activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA
      signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is
      considered a master regulator of SA signaling. NPR1 interacts with TGA
      transcription factors, ultimately leading to the activation of SA-dependent
      responses. SA has been shown to promote disease development caused by the
      necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the
      expression of two JA-dependent defense genes, proteinase inhibitors I and II. We
      show here that the transcription factor TGA1.a contributes to disease development
      caused by B. cinerea in tomato by suppressing the expression of proteinase
      inhibitors I and II. Finally, we present evidence that the SA-signaling pathway
      contributes to disease development caused by another necrotrophic pathogen,
      Alternaria solani, in tomato. Disease development promoted by SA through NPR1
      requires the TGA1.a transcription factor. These data highlight how necrotrophs
      manipulate the SAsignaling pathway to promote their disease in tomato.

PMID- 22950754
TI  - Expression profile and functional activity of peptide transporters in prostate
      cancer cells.
AB  - Peptide transporters are expressed predominantly in intestinal and renal
      epithelial cells. The functional expression of peptide transporters is also
      identified in other types of tissues, such as glia cells, macrophages, and the
      epithelia of the bile duct, the lungs, and the mammary glands. However, their
      presence and role are poorly understood in carcinomas. We explored the expression
      profile and functional activity of peptide transporters in the prostate cancer
      cell lines LNCaP, PC-3, and DU145. Quantitative real time RT-PCR (qRT-PCR) and
      Western blot were used to evaluate the expression profile of peptide transporter
      1 (PEPT1), peptide transporter 2 (PEPT2), peptide histidine transporter 1 (PHT1),
      and peptide histidine transporter 2 (PHT2) in these cells. LNCaP expresses high
      levels of PEPT2 and PHT1, while PC-3 demonstrates strong expression of PEPT1 and
      PHT1. DU145 shows only weak expression of PEPT1 and PHT1. Functional activities
      were studied in these cell lines using radiolabeled glycylsarcosine ([(3)H]Gly
      Sar) and l-histidine ([(3)H]-l-histidine). The uptake of [(3)H]Gly-Sar and [(3)H]
      l-histidine was time- and pH-dependent. A kinetic study showed that the uptake of
      Gly-Sar and l-histidine is saturable over the tested concentration range. The
      binding affinity (K(m)) and the maximal velocity (V(max)) exhibited in the three
      cell lines were consistent with the expression profiles we observed in qRT-PCR
      and Western blot analysis. A competitive inhibition study revealed that peptide
      transporters in prostate cancer cells exhibited broad substrate specificity with
      a preference for hydrophobic dipeptides, such as Leu-Leu. Fluorescence microscopy
      study revealed that the fluorescent dipeptide probe d-Ala-Lys-AMCA (a substrate
      of peptide transporters) specifically accumulated in the cytoplasm of LNCaP and
      PC-3, but not DU145 cells. Inhibiting the peptide transporter activity by Gly-Sar
      suppressed the growth of LNCaP and PC-3 cells. Our study indicated that PC-3
      cells can be established as a new cell culture model for PEPT1 study, and LNCaP
      can be used as a model for PEPT2 study. Moreover, our results suggested that
      peptide transporters are overexpressed in prostate cancer cells and can be
      adopted as a promising target for tumor-specific drug delivery.

PMID- 22950755
TI  - Long-term dietary exposure to lead in young European children: comparing a pan
      European approach with a national exposure assessment.
AB  - Long-term dietary exposures to lead in young children were calculated by
      combining food consumption data of 11 European countries categorised using
      harmonised broad food categories with occurrence data on lead from different
      Member States (pan-European approach). The results of the assessment in children
      living in the Netherlands were compared with a long-term lead intake assessment
      in the same group using Dutch lead concentration data and linking the consumption
      and concentration data at the highest possible level of detail. Exposures
      obtained with the pan-European approach were higher than the national exposure
      calculations. For both assessments cereals contributed most to the exposure. The
      lower dietary exposure in the national study was due to the use of lower lead
      concentrations and a more optimal linkage of food consumption and concentration
      data. When a pan-European approach, using a harmonised food categorisation system
      and "European" concentration data, results in a possible health risk related to
      the intake of an environmental chemical for a certain country, it is advisable to
      refine this assessment, as part of a tiered approach, using national occurrence
      data, including an optimised linkage between foods analysed and consumed for that
      country. In the case of lack of occurrence data, these data can be supplemented
      with data from the "European" concentration database or by generating additional
      concentration data at country level.

PMID- 22950757
TI  - One-step patterning of hybrid xerogel materials for the fabrication of disposable
      solid-state light emitters.
AB  - The one-step room-temperature micropatterning of a fluorophore-doped xerogel
      material on silicon oxide substrates is reported. The organo-alkoxysilane
      precursors and organic fluorescent dyes, as well as the polymerization
      experimental conditions, were tailored in order to obtain a highly homogeneous
      transparent material suitable for photonic applications. A thorough structural
      characterization was carried out by Fourier transform infrared (FT-IR)
      spectroscopy, (29)Si nuclear magnetic resonance ((29)Si NMR), thermogravimetric
      analysis (TGA), N(2) adsorption Brunauer-Emmett-Teller (BET) porosimetry, and
      confocal microscopy. These studies revealed a stable nonporous highly cross
      linked polymer network containing evenly dispersed fluorescent molecules. Xerogel
      microstructures having thicknesses between 4 and 80 MUm and height-to-width
      ratios between 0.04 and 4, as well as showing different geometries, from well
      arrays to waveguides, were patterned in a single step by micromolding in
      capillaries (MIMIC) soft lithographic technique. The reliability of the
      replication process was tested by bright-field optical microscopy and scanning
      electron microscopy (SEM) that show the close fidelity of the microstructures to
      the applied mold. The optical performance of the developed material was
      demonstrated by fabricating waveguides and evaluating their corresponding
      spectral response, obtaining absorption bands, at the expected excitation
      wavelengths of the corresponding fluorescent dyes and gain due to photonic re
      emission (fluorescence) at their corresponding dye emission wavelengths. The
      hybrid xerogel material and the application of the simple fabrication technology
      presented herein can be directly applied to the development of cost-effective
      photonic components, as could be light emitters, to be readily integrated in
      single-use lab-on-chip devices and other polymeric microsystems.

PMID- 22950756
TI  - Sigma factor-mediated plastid retrograde signals control nuclear gene expression.
AB  - Retrograde signalling from plastids to the nucleus is necessary to regulate the
      organelle's proteome during the establishment of photoautotrophy and fluctuating
      environmental conditions. Studies that used inhibitors of chloroplast biogenesis
      have revealed that hundreds of nuclear genes are regulated by retrograde signals
      emitted from plastids. Plastid gene expression is the source of at least one of
      these signals, but the number of signals and their mechanisms used to regulate
      nuclear gene expression are unknown. To further examine the effects of plastid
      gene expression on nuclear gene expression, we analyzed Arabidopsis mutants that
      were defective in each of the six sigma factor (SIG) genes that encode proteins
      utilized by plastid-encoded RNA polymerase to transcribe specific sets of plastid
      genes. We showed that SIG2 and SIG6 have partially redundant roles in plastid
      transcription and retrograde signalling to control nuclear gene expression. The
      loss of GUN1 (a plastid-localized pentatricopeptide repeat protein) is able to
      restore nuclear (but not plastid) gene expression in both sig2 and sig6, whereas
      an increase in heme synthesis is able to restore nuclear gene expression in sig2
      mutants only. These results demonstrate that sigma factor function is the source
      of at least two retrograde signals to the nucleus; one likely to involve the
      transcription of tRNA(Glu) . A microarray analysis showed that these two signals
      accounted for at least one subset of the nuclear genes that are regulated by the
      plastid biogenesis inhibitors norflurazon and lincomycin. Together these data
      suggest that such inhibitors can induce retrograde signalling by affecting
      transcription in the plastid. 

PMID- 22950759
TI  - Inferring genetic architecture of complex traits using Bayesian integrative
      analysis of genome and transcriptome data.
AB  - BACKGROUND: To understand the genetic architecture of complex traits and bridge
      the genotype-phenotype gap, it is useful to study intermediate -omics data, e.g.
      the transcriptome. The present study introduces a method for simultaneous
      quantification of the contributions from single nucleotide polymorphisms (SNPs)
      and transcript abundances in explaining phenotypic variance, using Bayesian whole
      omics models. Bayesian mixed models and variable selection models were used and,
      based on parameter samples from the model posterior distributions, explained
      variances were further partitioned at the level of chromosomes and genome
      segments. RESULTS: We analyzed three growth-related traits: Body Weight (BW),
      Feed Intake (FI), and Feed Efficiency (FE), in an F2 population of 440 mice. The
      genomic variation was covered by 1806 tag SNPs, and transcript abundances were
      available from 23,698 probes measured in the liver. Explained variances were
      computed for models using pedigree, SNPs, transcripts, and combinations of these.
      Comparison of these models showed that for BW, a large part of the variation
      explained by SNPs could be covered by the liver transcript abundances; this was
      less true for FI and FE. For BW, the main quantitative trait loci (QTLs) are
      found on chromosomes 1, 2, 9, 10, and 11, and the QTLs on 1, 9, and 10 appear to
      be expression Quantitative Trait Locus (eQTLs) affecting gene expression in the
      liver. Chromosome 9 is the case of an apparent eQTL, showing that genomic
      variance disappears, and that a tri-modal distribution of genomic values
      collapses, when gene expressions are added to the model. CONCLUSIONS: With
      increased availability of various -omics data, integrative approaches are
      promising tools for understanding the genetic architecture of complex traits.
      Partitioning of explained variances at the chromosome and genome-segment level
      clearly separated regulatory and structural genomic variation as the areas where
      SNP effects disappeared/remained after adding transcripts to the model. The
      models that include transcripts explained more phenotypic variance and were
      better at predicting phenotypes than a model using SNPs alone. The predictions
      from these Bayesian models are generally unbiased, validating the estimates of
      explained variances.

PMID- 22950758
TI  - Age-related loss of nitric oxide synthase in skeletal muscle causes reductions in
      calpain S-nitrosylation that increase myofibril degradation and sarcopenia.
AB  - Sarcopenia, the age-related loss of muscle mass, is a highly-debilitating
      consequence of aging. In this investigation, we show sarcopenia is greatly
      reduced by muscle-specific overexpression of calpastatin, the endogenous
      inhibitor of calcium-dependent proteases (calpains). Further, we show that
      calpain cleavage of specific structural and regulatory proteins in myofibrils is
      prevented by covalent modification of calpain by nitric oxide (NO) through S
      nitrosylation. We find that calpain in adult, non-sarcopenic muscles is S
      nitrosylated but that aging leads to loss of S-nitrosylation, suggesting that
      reduced S-nitrosylation during aging leads to increased calpain-mediated
      proteolysis of myofibrils. Further, our data show that muscle aging is
      accompanied by loss of neuronal nitric oxide synthase (nNOS), the primary source
      of muscle NO, and that expression of a muscle-specific nNOS transgene restores
      calpain S-nitrosylation in aging muscle and prevents sarcopenia. Together, the
      findings show that in vivo reduction of calpain S-nitrosylation in muscle may be
      an important component of sarcopenia, indicating that modulation of NO can
      provide a therapeutic strategy to slow muscle loss during old age.

PMID- 22950761
TI  - Body image during pregnancy: an evaluation of the suitability of the Body
      Attitudes Questionnaire.
AB  - BACKGROUND: Available data suggest that body dissatisfaction is common during
      pregnancy and may even be a precursor to post-natal depression. However, in order
      to accurately identify at-risk women, it is essential to first establish that
      body image measures function appropriately in pregnant populations. Our study
      examines the suitability of the Body Attitudes Questionnaire (BAQ) for measuring
      body dissatisfaction among pregnant women by comparing the psychometric
      functioning of the BAQ: (1) across key phases of pregnancy, and (2) between
      pregnant and non-pregnant women. METHODS: A total of 176 pregnant women from
      Melbourne, Victoria filled out a questionnaire battery containing demographic
      questions and the Body Attitudes Questionnaire at 16, 24, and 32 weeks during
      pregnancy. A comparison group of 148 non-pregnant women also completed the
      questionnaire battery at Time 1. Evaluations of the psychometric properties of
      the BAQ consisted of a series of measurement invariance tests conducted within a
      structural equation modelling framework. RESULTS: Although the internal
      consistency and factorial validity of the subscales of the BAQ were established
      across time and also in comparisons between pregnant and non-pregnant women,
      measurement invariance tests showed non-invariant item intercepts across
      pregnancy and also in comparison with the non-pregnant subgroup. Inspection of
      modification indices revealed a complex, non-uniform pattern of differences in
      item intercepts across groups. CONCLUSIONS: Collectively, our findings suggest
      that comparisons of body dissatisfaction between pregnant and non-pregnant women
      (at least based on the BAQ) are likely to be conflated by differential
      measurement biases that serve to undermine attempts to accurately assess level of
      body dissatisfaction. Researchers should be cautious in assessments of body
      dissatisfaction among pregnant women until a suitable measure has been
      established for use in this population. Given the fact that body dissatisfaction
      is often associated with maladaptive behaviours, such as unhealthy eating and
      extreme weight loss behaviours, and with ante-and post-natal depression, that
      have serious negative implications for women's health and well-being, and
      potentially also for the unborn foetus during pregnancy, developing a suitable
      body image screening tool, specific to the perinatal period is clearly warranted.

PMID- 22950760
TI  - Malondialdehyde measurement in oxidized foods: evaluation of the
      spectrophotometric thiobarbituric acid reactive substances (TBARS) test in
      various foods.
AB  - The ability of the spectrophotometric thiobarbituric acid reactive substances
      (TBARS) test to determine malondialdehyde (MDA) in various food matrices was
      evaluated. MDA was extracted from the foods; the extract reacted with
      thiobarbituric acid (TBA); and the formed TBA-MDA adduct was measured
      spectrophotometricaly at 532 nm. In parallel, the TBA-MDA adduct was analyzed
      with high-performance liquid chromatography (HPLC) coupled with fluorescence
      detection. Oils and unprocessed and uncooked meat and fish products did not
      exhibit any significant difference in the amount of MDA measured by the two
      methods, indicating that the major substance reacting with TBA and forming an
      adduct that absorbs at 532 nm was MDA. However, in products such as dry nuts,
      pork sausages, cooked fish, and gouda cheese, an overestimation of MDA was
      observed, indicating that TBARS test was unsuitable for accurate determination of
      MDA. Furthermore, the results in the present work suggest that the overestimation
      of MDA by the TBARS test as it was applied is related to the interference of
      other than secondary lipid oxidation products.

PMID- 22950763
TI  - State of psychiatry in Europe.

PMID- 22950762
TI  - Impact of organic carbon on the stability and toxicity of fresh and stored silver
      nanoparticles.
AB  - Studies investigating the impact of particle size and capping agents on
      nanosilver toxicity in pristine laboratory conditions are becoming available.
      However, the relative importance of known environmental mitigating factors for
      dissolved silver remains poorly characterized for nanosilver in context with
      existing predictive toxicity models. This study investigated the implications of
      freshly prepared versus stored 20 and 100 nm nanosilver stocks to freshwater
      zooplankton (Ceriodaphnia dubia) in presence and absence of dissolved organic
      carbon (DOC). Results indicated that while the acute toxicity of nanosilver
      decreased significantly with larger size and higher DOC, storage resulted in
      significant increases in toxicity and ion release. The most dramatic decrease in
      toxicity due to DOC was observed for the 20 nm particle (2.5-6.7 fold decrease),
      with more modest toxicity reductions observed for the 100 nm particle (2.0-2.4
      fold) and dissolved silver (2.7-3.1 fold). While a surface area dosimetry
      presented an improvement over mass when DOC was absent, the presence of DOC
      confounded its efficacy. The fraction of dissolved silver in the nanosilver
      suspensions was most predictive of acute toxicity regardless of system
      complexity. Biotic Ligand Model (BLM) predictions based on the dissolved fraction
      in nanosilver suspensions were comparable to observed toxicity.

PMID- 22950764
TI  - The state of psychiatry in Europe: facing the challenges, developing consensus.
AB  - All European countries are facing the challenge to address the very high
      prevalence of mental disorders with limited mental health resources, resulting in
      a treatment gap. Countries have drafted mental health strategies, replacing
      institutions with community based models of care with the aim to offer good and
      decent care. Psychiatry across Europe is very diverse, whether one considers
      models of care, resources, ways of working or training. Variation within
      countries, due to regionalization, can be as large as across frontiers. Valid
      comparisons of service delivery and their outcomes is essential for
      identification and dissemination of effective and efficient practice, but
      hampered by widely used but poorly defined terminology such as 'primary care' and
      'community services', or assumptions about common ways of working. There is also
      still a lack of standardisation of outcome indicators. The combination of high
      morbidity and low supply in the presence of effective interventions is a strong
      argument in favour of investment, especially at times of growing need. It is
      necessary to support this argument with consistent evidence of improved outcome.
      It is essential that international groups now accept the challenge to reach
      consensus in order to advocate for more mental health resources.

PMID- 22950765
TI  - The state of psychiatry in the Czech Republic.
AB  - This overview of Czech psychiatry begins with a brief review of its history;
      outlines its social, political and economic determinants and then describes the
      field itself. Both epidemiological and service-related information are discussed,
      together with the issues for mental health personnel, education and research. The
      heavy burden of communist history pervades most areas and must be taken into
      account in the specific characteristics that influence both the current situation
      and future prospects of Czech psychiatry. This consideration is essential for
      orientation in the field and to understand Czech particularities. The greatest
      challenges, however, originate from the fundamental changes that are going on in
      the world today. These challenges reach beyond national boundaries and include
      such phenomena as globalization, migration, ageing population, growing burden of
      mental ill health, the still prevailing stigma towards psychiatry, and the
      psychological roots and consequences of current financial and societal crises.

PMID- 22950766
TI  - The state of psychiatry in Belgium.
AB  - Belgium, at the crossroads of different cultures, developed complex governmental
      structures hindering the development of comprehensive mental health policies. A
      total of 10.2% of the gross domestic product is spent on healthcare but only 6.1%
      of this total expenditure goes to mental health. Although mental healthcare is
      largely accessible and offers high levels of quality, it is questionable whether
      this can be maintained, given the economic climate. The collection of
      epidemiological data is problematic due to the different ways registration takes
      place within different care systems and the complexity of the state structure and
      its consecutive constitutional reforms. Coming from a largely hospital-driven
      psychiatric care, mental healthcare reforms of past decades have created more
      community-based care and new care pathways, still an on-going process. Psychiatry
      as a profession is currently challenged. Teaching mental health issues remains
      extremely limited within medical schools, resources for research are
      disproportionally limited, and working conditions less favourable, all this
      compared with other specialisms. Hence few graduates choose a career in
      psychiatry. Changing the public perception of what psychiatry is about,
      redefining the identity of psychiatrists as medical specialists, and their work
      have become important challenges for the next future.

PMID- 22950768
TI  - The state of psychiatry in Greece.
AB  - Greek psychiatry is presently in a transitional period. Following a large-scale
      reform effort that started in the mid 1980s, de-institutionalization and
      establishment of numerous community services has been achieved to a great extent.
      However, sectorization, development of primary care policies, inter-sectoral
      communication and long-range planning have not been achieved and deficiencies in
      the provision of care for children, adolescents, old people, individuals with
      autism, with intellectual disabilities and with eating disorders as well as
      deficiencies in forensic psychiatric services have been identified. Thus, the
      Greek psychiatric reform is an unfinished reform. The financial crisis that has
      recently hit the country has had a serious impact on the population and
      especially on vulnerable groups such as individuals with psychiatric disorders.
      Continuation of psychiatric reform to its desired extent has become problematic.
      This situation calls for re-orientation of the national mental health strategy
      towards more realistic and priority-orientated goals, i.e. securing a
      satisfactory level of function of the existing services, persisting in the
      implementation of the basic targets of psychiatric reform, creating the necessary
      infrastructure but avoiding the creation of expensive facilities of secondary
      importance.

PMID- 22950767
TI  - State of psychiatry in Denmark.
AB  - Danish psychiatry has gone through profound changes over the past two to three
      decades, reducing inpatient-based treatment and increasing outpatient treatment
      markedly. The number of patients treated has almost doubled, and the diagnostic
      profile has broadened, now including a substantial number of common mental
      disorders, in particular depression and anxiety. Furthermore, 'new' diagnostic
      groups are represented in the treatment statistics with steeply increasing
      incidences, e.g. attention deficit hyperactivity disorder (ADHD) and eating
      disorders, especially in the outpatient part of the statistics. Over the same 30
      years, the number of available beds has been reduced by 60-70%; however, as the
      length of stay of inpatients has been reduced markedly, the departments are still
      able to treat a high number of patients. The financial budgeting of psychiatry is
      not increasing equivalently to the somatic specialities, handicapping development
      in psychiatry. Action has been taken to increase research activity in psychiatry.
      This is facilitated by an increasing interest among medical students and young
      graduate physicians attracted by the neuropsychiatric paradigm, rapidly
      implemented in Danish psychiatry.

PMID- 22950769
TI  - State of psychiatry in Hungary.
AB  - Hungary has a tradition both in biological psychiatry and psychotherapy, and for
      decades developed together with neurology. From the mid 1980s the speed of
      development of psychiatry started lagging behind expected standards. Psychiatric
      care, research and teaching were hit hard in 2007 by unprecedented closures of
      facilities and budget reductions. Although suicide rates have decreased since the
      mid 1980s, the country has still the second highest rate in the European Union.
      The high prevalence of alcohol use and the rapidly increasing prevalence of
      illicit drug use contribute to comorbidity and related behavioural issues,
      including the increased frequency of severe violent events committed by people
      with psychiatric disorders, which have not been properly addressed. The country
      expects the first major restructuring of its healthcare starting in 2012 since
      the major political changes of 1989/1990. The profession, patients and their
      caregivers should use this opportunity to modernize psychiatry in Hungary.

PMID- 22950770
TI  - State of psychiatry in Italy 35 years after psychiatric reform. A critical
      appraisal of national and local data.
AB  - Thirty-four years have elapsed since the passing of the Italian Law 180, the
      reform law that marked the transition from a hospital-based system of care to a
      model of community psychiatry that was designed to be an alternative to, rather
      than to complement, the old hospital-centred services. The main principle of Law
      180 is that psychiatric patients have the right to be treated the same way as
      patients with other diseases and only voluntary treatments are allowed, with a
      few exceptions that are strictly regulated. The main features and consequences of
      the Italian reform are initially reviewed; national and local level experiences
      and epidemiological data are then analysed in order to highlight and disentangle
      the 'active ingredients' of the Italian experience. A public health attitude with
      the capacity to network good practice in service organization by giving voice to
      successful experiences and promoting health service research, apart from some
      local services, is still generally lacking. Furthermore, it is still difficult to
      provide an evidence-based reply to the question: can a l'Italienne community-care
      be exported elsewhere?

PMID- 22950771
TI  - The state of psychiatry in the Netherlands: strength by quality, influence by
      capabilities.
AB  - Psychiatry and mental healthcare in the Netherlands has a long history of
      institutional care, slowly more adapted to the community, but differentiated from
      mainstream healthcare in terms of organization and remuneration. It is in a
      crucial phase of reconsideration. Along with harsh cuts on the budgets in
      healthcare, the field is in transition where training is concerned. The good news
      is that in fruitful cooperation the government and all spcialist parties involved
      in mental healthcare are on the verge of reaching an important agreement that
      should make mental healthcare more patient centred, affordable and accessible for
      those who need it. The bad news that needs serious consideration and ongoing
      action is that mental health problems are still highly stigmatized and that as a
      result the government could impose an unjust and unfair own financial
      contribution for users in mental care as a means of lowering the costs in the
      field.

PMID- 22950772
TI  - History and current condition of Russian psychiatry.
AB  - Russian psychiatry has a dramatic history, and until now has been at a
      transitional stage of development. It is facing problems not only common in world
      psychiatry, but also specific to eastern Europe, in particular Russia. Starting
      from the beginning of the 1990s, considerable changes have occurred in
      psychiatry, especially after 1992 when the law on psychiatric care and guarantees
      of citizens' rights in its provision was adopted. It became the ideological and
      legislative basis for reforms. However, there are definite obstacles to
      structural reforms in psychiatry. They are unfavourable technical conditions in
      many psychiatric clinics, hypercentralization of psychiatric services, shortage
      of clinical psychologists and social workers in psychiatry, some difficulties in
      cooperation between psychiatric and general medical institutions. Economic
      difficulties in the transition period of Russia's social development prevent the
      overcoming of these problems. They are being actively discussed and some of them
      are being gradually solved, e.g. the organization of team work in mental health
      services, the increasing number of specialists on social work, and the
      involvement of non-government organizations in psychosocial rehabilitation.

PMID- 22950773
TI  - The emergence of psychiatry in Portugal: from its roots to now.
AB  - The authors describe the panorama of psychiatry in Portugal. Starting with the
      emergence of psychiatry with a humanizing stamp, in 1848, cover the six major
      periods of development of this speciality in Portugal, proposed by Barahona
      Fernandes, and add a seventh period that corresponds to the last quarter of the
      20th century. They highlight the figures with greater emphasis during these
      periods, as well as their contributions to the speciality, not forgetting the
      essential role of Ordens Hospitaleiras (Hospitallers Orders). The transition
      period for mental health is examined in the light of the socio-political
      conditions of that time. The authors then describe both the teaching of
      psychiatry, and the actual training program of that medical speciality in
      Portugal. In this regard, the authors address the on-going mental health policies
      and their consequences on the current situation on the ground. Aspects such as
      the prevalence of mental disorders in Portugal, the current status of training in
      psychiatry, the sub-specialities of psychiatry and allied professions, the main
      areas of research, workforce issues and human rights issues are also analysed.
      Finally, the authors end with a few words about the future and the challenges of
      psychiatry in Portugal.

PMID- 22950774
TI  - State of psychiatry in Serbia--problems, advances and perspectives.
AB  - Serbia has been exposed to many severe stressors during the last 20 years and as
      a result there is an increase of the incidence of mental health problems in its
      population, so that mental disorders are the second largest public health
      problem, after cardiovascular diseases. The National Strategy for Development of
      Mental Health Care was approved by the government in January 2007 which initiated
      the reform of psychiatry in the country. The major advantages of the existing
      organization of mental healthcare are a sufficient number of psychiatric services
      and the number of well educated professionals, but there are considerable
      problems in big psychiatric hospitals which are significantly overcrowded with
      patients, as well as with the lack of a network of community services. In the
      future, key points of mental health reform aim to focus on improved cooperation
      and collaboration between primary, secondary and tertiary healthcare levels,
      definition of catchment areas and responsibilities, continuing education of
      general practitioners in mental health issues, and better cooperation between
      psychiatric and social welfare institutions. The profile of the Institute for
      Mental Health is described as a case of good practice in the field of mental
      healthcare in Serbia.

PMID- 22950775
TI  - The state of psychiatry in Spain.
AB  - The 1986 General Health Act and the so-called 'psychiatric reform' were key
      issues in the development of the mental healthcare system (MHCS) in Spain. The
      World Health Organization Declaration and Action Plan on Mental Health in 2005
      gave it a revitalizing impetus and resulted in the first National Health System
      (NHS) Mental Health Strategy in 2006. A literature search was performed using
      MEDLINE, Spanish journals, reference lists, national databases, and European and
      Spanish official documents to describe the current state of the MHCS in Spain.
      The main results were: (1) existence of great variability among the autonomous
      communities with respect to mental health resources and provision of care; (2)
      lack of national epidemiological information on mental disorders with the
      exception of substance use disorders and suicide, which comprise powerful
      longitudinal national data, (3) training in psychiatry is well established,
      although there is no specialism of child and adolescent psychiatry, and (4) a
      dramatic increase in scientific productivity in the last decade among research
      groups, in part due to the creation of the Spanish Mental Health Network, the
      Centro de Investigacion Biomedica en Red en el Area de Salud Mental (CIBERSAM).
      Quantifiable and reliable indicators are needed to provide efficient monitoring
      and analysis of epidemiological events and subsequently to understand the status
      of the Spanish MHCS.

PMID- 22950776
TI  - The state of psychiatry in Sweden.
AB  - The number of practising psychiatrists in Sweden has increased by nearly 30%
      between the years 1995-2009; however, the profession has suffered serious
      recruitment difficulties. The Swedish National Board of Health and Welfare
      estimated that about 5-10% of the population is in need of psychiatric treatment,
      but only 3-4% seek psychiatric care. Among patients who receive psychiatric care,
      approximately 47% are treated with psychopharmacology, 13% are treated with
      psychotherapy and 40% receive both treatments. There are still challenges facing
      Swedish psychiatry: reduction in waiting times for psychiatric care, broader
      accessibility of evidence-based treatment methods for all groups of psychiatric
      patients both in rural and urban areas, and targeting the needs of immigrants and
      refugees. The allocation of resources to psychiatric research, and development of
      novel treatment methods are crucially needed. The Swedish government is strongly
      committed to decreasing the number of suicides, as there are approximately 1,400
      individuals lost to suicide every year in a country with a population of around
      10 million. Given that nearly 20% of all suicides are amongst psychiatric
      inpatients, a regulation has been passed regarding the analysis of all completed
      suicides in the healthcare system. Results from these analyses can be used for
      increasing quality of treatment.

PMID- 22950777
TI  - The organization of psychiatric care in France: current aspects and future
      challenges.
AB  - In the last four decades, psychiatric care in France has led to the development
      of catchment area-based service provision. Within each geographical area teams
      are now responsible for psychiatric care both at outpatient and inpatient levels.
      However, financial and economic constraints have led to a reduction in beds and
      staffing levels. The numbers of psychiatrists in private practice has remained
      more or less the same over the years due to steady demand and other factors. As
      in many other western European countries, de-institutionalization has been a
      major driver in the evolution of psychiatric care delivery in France. This is
      linked with several developments, including the introduction of more efficient
      pharmaceutical drugs which have reduced the likelihood of relapse. Other factors
      which have influenced this include the progressive 'de-stigmatization' of
      psychiatric disorders and policy changes leading to significant bed reduction.
      All of these factors are inter-linked and have influenced psychiatric care
      delivery. In this paper we provide an overview of the current state of
      psychiatric care and its delivery in France.

PMID- 22950778
TI  - Austria: a brief report.
AB  - In spite of a large population base, Austria spends around 11% of gross domestic
      product on healthcare for its citizens. Psychiatric services include both
      inpatient services and community-based services, and the government has initiated
      many educational programmes. The government has a mental health plan which is the
      responsibility of the state rather than the federal government, and has a recent
      suicide prevention programme.

PMID- 22950779
TI  - Psychiatry in Germany 2012.
AB  - Healthcare in Germany is characterized by a dichotomy of a private and a public
      healthcare sector, which also pertains to mental healthcare. While the prevalence
      figures of mental disorders in Germany remained fairly constant over the last 15
      years, utilization rates of healthcare services due to mental disorders increased
      by 70-80% including inpatient and outpatient services, sick leave cases and cases
      of early retirement due to mental disorders. Several challenges are currently
      evident for mental healthcare in Germany, ranging from interesting a sufficient
      number of medical students for this field of medicine, dealing with the yet
      unforeseeable consequences of a novel mental hospital remuneration system, better
      integration of services and remuneration providers, to elucidating the causes of
      the increasing utilization rates. Mental healthcare research will take centre
      stage in addressing these challenges.

PMID- 22950780
TI  - State of psychiatric services in the UK.
AB  - In the UK, medical services, including psychiatric services, are all delivered
      under the broad umbrella of the National Health Service, which provides services
      free at the point of contact and according to need. In this paper we provide a
      brief historical overview of the National Health Service and illustrate changes
      leading to changes in the delivery of psychiatric services. Historical and
      political developments have contributed to changes in the way services develop
      and are delivered. The introduction of community mental health services and
      functionalized teams are a reflection of policy changes. We attempt here to offer
      a brief overview and note the lessons from history along with changes in
      healthcare delivery, development of new teams and psychiatric response to
      political and economic changes.

PMID- 22950781
TI  - Metallic conduction and large electron-phonon-impurity interference effect in
      single TiSi nanowires.
AB  - We report on the first electrical characterizations of single-crystalline TiSi
      nanowires (NWs) synthesized by chemical vapor deposition reactions. By utilizing
      the focused-ion-beam-induced deposition technique, we have delicately made four
      probe contacts onto individual NWs. The NW resistivities have been measured
      between 2 and 300 K, which reveal overall metallic conduction with small residual
      resistivity ratios in the NWs. Surprisingly, we find that the effect due to the
      interference processes between the elastic electron scattering and the electron
      phonon scattering largely dominates over the usual Boltzmann transport even at
      room temperature. Such prominent electron-phonon-impurity interference effect is
      ascribed to the presence of large amounts of disorder and high Debye temperatures
      in TiSi NWs.

PMID- 22950782
TI  - Differential oxidative modification of proteins in MRL+/+ and MRL/lpr mice:
      Increased formation of lipid peroxidation-derived aldehyde-protein adducts may
      contribute to accelerated onset of autoimmune response.
AB  - Even though reactive oxygen species (ROS) have been implicated in SLE
      pathogenesis, the contributory role of ROS, especially the consequences of
      oxidative modification of proteins by lipid peroxidation-derived aldehydes
      (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) in eliciting an
      autoimmune response and disease pathogenesis remains largely unexplored. MRL/lpr
      mice, a widely used model for SLE, spontaneously develop a condition similar to
      human SLE, whereas MRL+/+ mice with the same MRL background, show much slower
      onset of SLE. To assess if the differences in the onset of SLE in the two
      substrains could partly be due to differential expression of LPDAs and to provide
      evidence for the role of LPDA-modified proteins in SLE pathogenesis, we
      determined the serum levels of MDA-/HNE-protein adducts, anti-MDA-/HNE-protein
      adduct antibodies, MDA-/HNE-protein adduct specific immune complexes, and various
      autoantibodies in 6-, 12- and 18-week old mice of both substrains. The results
      show age-related increases in the formation of MDA-/HNE-protein adducts, their
      corresponding antibodies and MDA-/HNE-specific immune complexes, but MRL/lpr mice
      showed greater and more accelerated response. Interestingly, a highly positive
      correlation between increased anti-MDA-/HNE-protein adduct antibodies and
      autoantibodies was observed. More importantly, we further observed that HNE-MSA
      caused significant inhibition in antinuclear antibodies (ANA) binding to nuclear
      antigens. These findings suggest that LPDA-modified proteins could be important
      sources of autoantibodies and CICs in these mice, and thus contribute to
      autoimmune disease pathogenesis. The observed differential responses to LPDAs in
      MRL/lpr and MRL+/+ mice may, in part, be responsible for accelerated and delayed
      onset of the disease, respectively.

PMID- 22950783
TI  - Identification of a foldaxane kinetic byproduct during guest-induced single to
      double helix conversion.
AB  - An aromatic oligoamide sequence was designed and synthesized to fold in a single
      helix having a large cavity and to behave as a host for a dumbbell-shaped guest
      derived from tartaric acid. NMR, molecular modeling, and circular dichroism (CD)
      evidence demonstrated the rapid formation of this 1:1 host-guest complex and
      induction of the helix handedness of the host by the guest. This complex was
      found to be a long-lived kinetic supramolecular byproduct, as it slowly
      transformed into a 2:2 host-guest complex with two guest molecules bound at the
      extremities of a double helix formed by the host, as shown by NMR and CD
      spectroscopy and a solid-state structure. The guest also induced the handedness
      of the double helical host, but with an opposite bias. The chiroptical properties
      of the system were thus found to revert with time as the 1:1 complex formed
      first, followed by the 2:2 complex.

PMID- 22950785
TI  - Vibrational spectra and structures of neutral Si(m)C(n) clusters (m + n = 6):
      sequential doping of silicon clusters with carbon atoms.
AB  - Vibrational spectra of mixed silicon carbide clusters Si(m)C(n) with m + n = 6 in
      the gas phase are obtained by resonant infrared-vacuum-ultraviolet two-color
      ionization (IR-UV2CI for n <= 2) and density functional theory (DFT)
      calculations. Si(m)C(n) clusters are produced in a laser vaporization source, in
      which the silicon plasma reacts with methane. Subsequently, they are irradiated
      with tunable IR light from an IR free electron laser before they are ionized with
      UV photons from an F(2) laser. Resonant absorption of one or more IR photons
      leads to an enhanced ionization efficiency for Si(m)C(n) and provides the size
      specific IR spectra. IR spectra measured for Si(6), Si(5)C, and Si(4)C(2) are
      assigned to their most stable isomers by comparison with calculated linear
      absorption spectra. The preferred Si(m)C(n) structures with m + n = 6 illustrate
      the systematic transition from chain-like geometries for bare C(6) to three
      dimensional structures for bare Si(6). In contrast to bulk SiC, carbon atom
      segregation is observed already for the smallest n (n = 2).

PMID- 22950784
TI  - A device for performing lateral conductance measurements on individual double
      stranded DNA molecules.
AB  - A nanofluidic device is described that is capable of electrically monitoring the
      driven translocation of DNA molecules through a nanochannel. This is achieved by
      intersecting a long transport channel with a shorter orthogonal nanochannel. The
      ionic conductance of this transverse nanochannel is monitored while DNA is
      electrokinetically driven through the transport channel. When DNA passes the
      intersection, the transverse conductance is altered, resulting in a transient
      current response. In 1 M KCl solutions, this was found to be a current
      enhancement of 5-25%, relative to the baseline transverse ionic current. Two
      different device geometries were investigated. In one device, the DNA was
      detected after it was fully inserted into and translocating through the transport
      nanochannel. In the other device, the DNA was detected while it was in the
      process of entering the nanochannel. It was found that these two conditions are
      characterized by different transport dynamics. Simultaneous optical and
      electrical monitoring of DNA translocation confirmed that the transient events
      originated from DNA transport through the nanochannel intersection.

PMID- 22950786
TI  - Design of electrical conductive composites: tuning the morphology to improve the
      electrical properties of graphene filled immiscible polymer blends.
AB  - Polystyrene (PS) and poly(methyl methacrylate) (PMMA) blends filled with
      octadecylamine-functionalized graphene (GE-ODA) have been fabricated to obtain
      conductive composites with a lower electrical percolation threshold according to
      the concept of double percolation. The dependence of the electrical properties of
      the composites on the morphology is examined by changing the proportion of PS and
      PMMA. Our results reveal that the electrical conductivity of the composites can
      be optimal when PS and PMMA phases form a cocontinuous structure and GE-ODA
      nanosheets are selectively located and percolated in the PS phase. For the
      PS/PMMA blend (50w/50w), the composites exhibit an extremely low electrical
      percolation threshold (0.5 wt %) because of the formation of a perfect double
      percolated structure. Moreover, the rheological properties of the composites are
      also measured to gain a fundamental understanding of the relationship between
      microstructure and electrical properties.

PMID- 22950787
TI  - Sitagliptin: anti-platelet effect in diabetes and healthy volunteers.
AB  - Sitagliptin, a selective dipeptidyl peptidase-4 inhibitor drug is used to treat
      type-2 diabetes (T2DM). We investigated the anti-platelet activity of sitagliptin
      in patients with T2DM and in in vitro samples obtained from healthy humans.
      Patients with T2DM (27 male + 23 female) were selected and followed up before
      (control) and after treatment with sitagliptin for up to 3 months. Platelets were
      isolated from the blood of sitagliptin treated patients and controls. Patients
      with T2DM treated with sitagliptin for 1and 3 months, showed 10 +/- 2% and 30 +/-
      5% inhibition of platelet aggregation, respectively. For the in vitro study,
      platelets from 10 normal humans (n = 10) were isolated. Platelet aggregation,
      intracellular free calcium and tyrosine phosphorylation of multiple proteins were
      measured by aggregometer, spectrofluorometer and western blotting, respectively.
      Platelets pre-treated with 5 and 10 ug/ml of sitagliptin, showed 25 +/- 4% and 40
      +/- 6% inhibition of thrombin-induced platelet aggregation, respectively.
      Sitagliptin decreased intracellular free calcium (2.5-fold) and tyrosine
      phosphorylation of multiple proteins in thrombin-induced platelet activation.
      Sitagliptin inhibited platelet aggregation in T2DM as well as in healthy humans.
      Sitagliptin has significant concentration-dependent anti-platelet activity. This
      activity was due to its inhibitory effect on intracellular free calcium and
      tyrosine phosphorylation.

PMID- 22950788
TI  - Utility of thyroglobulin measurements in fine-needle aspirates of space occupying
      lesions in the thyroid bed after thyroid cancer operations.
AB  - BACKGROUND: Ultrasound, and sometimes cytology, cannot differentiate between
      recurrent or persistent thyroid cancer and benign forms of space occupying
      lesions (SOLs) in the thyroid bed, including unsuspected thyroid remnants, that
      are noted several months to years after thyroidectomy (Tx) for thyroid cancer.
      The purpose of the present study was to evaluate the hypothesis that measurement
      of thyroglobulin (Tg) in fine-needle aspirates from these lesions might help
      differentiate between benign and malignant SOLs in the thyroid bed. METHODS: We
      studied 47 lesions in the thyroid bed from 43 patients who, 8-240 months
      previously, had 43 Txs for thyroid cancer. Eleven patients had a lobectomy and 32
      patients had a total Tx. Also, some patients had radioactive iodine (RAI)
      ablation after their thyroid surgery and some did not. "Recurrence" was defined
      as the SOL, which was confirmed by cytological or histopathological results.
      "Benign SOL" was defined as a focal lesion, which was benign or nondiagnostic
      result on cytology and for which there was no RAI uptake on whole-body
      scintigraphy with both negative serum Tg and Tg antibodies. Diagnostic
      performances of fine-needle aspiration cytology (FNAC), FNA-Tg, and combining
      FNAC with FNA-Tg level were assessed for detection of malignant SOL. The
      diagnostic performance of FNA-Tg was assessed using three threshold values: 1
      ng/mL, 10 ng/mL, and an FNA-Tg/serum-Tg ratio of 1.0. RESULTS: FNA-Tg level and
      combining FNA-Tg levels with FNAC had higher sensitivities (100% in all three
      threshold values) and diagnostic accuracies (91.5%-95.7%) than FNAC alone
      (sensitivity of 85.3%, accuracy of 89.4%) in all threshold values. In both the
      RAI ablation and non-RAI ablation groups, the FNA-Tg levels and combining the FNA
      Tg levels with FNAC had a higher sensitivity and diagnostic accuracy than FNAC
      alone with threshold values of 10 ng/mL and FNA-Tg/serum-Tg ratio of 1.0. The non
      RAI ablation group did not have a different diagnostic accuracy than the RAI
      ablation group in all threshold values (p>0.05). FNA-Tg level showed a negative
      predictive value of 100% in all threshold values, in both the RAI ablation and
      the non-RAI ablation groups. CONCLUSIONS: Measurement of Tg levels in the FNA of
      SOLs in the thyroid bed can be helpful in diagnosing tumor recurrence, because an
      FNA-Tg level lower than the threshold value has the added value of suggesting a
      benign lesion rather than tumor recurrence.

PMID- 22950790
TI  - Introducing the Global Research Interprofessional Network (GRIN).

PMID- 22950789
TI  - Dichloroacetonitrile and dichloroacetamide can form independently during
      chlorination and chloramination of drinking waters, model organic matters, and
      wastewater effluents.
AB  - The increasing usage of organic nitrogen-rich wastewater- or algal-impacted
      waters, and chloramines for secondary disinfection, raises concerns regarding the
      formation of haloacetonitriles, haloacetamides and other nitrogenous disinfection
      byproducts (N-DBPs). Previous research obtained contradictory results regarding
      the relative importance of chlorination or chloramination for promoting these
      byproducts, but applied chlorine and chloramines at different doses and exposure
      periods. Additionally, mechanistic work, mostly using model precursors, suggested
      that haloacetonitrile and haloacetamide formation should be correlated because
      hydrolysis of haloacetonitriles forms haloacetamides. In this work, the formation
      of dichloroacetonitrile (DCAN) and dichloroacetamide (DCAcAm) were compared
      across a range of chlorine and chloramine exposures for drinking waters,
      wastewater effluents, algal extracellular polymeric substances (EPS), NOM
      isolates and model precursors. While chlorination favored formation of DCAN over
      DCAcAm, chloramination nearly always formed more DCAcAm than DCAN, suggesting the
      existence of haloacetamide formation pathways that are independent of the
      hydrolysis of haloacetonitriles. Experiments with asparagine as a model precursor
      also suggested DCAcAm formation without a DCAN intermediate. Application of (15)N
      labeled monochloramine indicated initial rapid formation of both DCAN and DCAcAm
      by pathways where the nitrogen originated from organic nitrogen precursors.
      However, slower formation occurred by pathways involving chloramine incorporation
      into organic precursors. While wastewater effluents and algal EPS tended to be
      more potent precursors for DCAN during chlorination, humic materials were more
      potent precursors for DCAcAm during chlorination and for both DCAN and DCAcAm
      during chloramination. These results suggest that, rather than considering
      haloacetamides as haloacetonitrile hydrolysis products, they should be treated as
      a separate N-DBP class associated with chloramination. While use of impaired
      waters may promote DCAN formation during chlorination, use of chloramines may
      promote haloacetamide formation for a wider array of waters.

PMID- 22950791
TI  - Interprofessional education accreditation standards in the USA: a comparative
      analysis.
AB  - Interprofessional education (IPE) and interprofessional collaborative practice
      (IPCP) will play a prominent role in the future of health professions' education
      and healthcare delivery in the USA and internationally. To assess the
      accreditation mandate for IPE in the USA, content analysis of IPE-related
      accreditation statements for all practice-level degrees in dentistry, medicine,
      nursing, occupational therapy, pharmacy, physical therapy, physician assistant,
      psychology, public health and social work was performed. Eighteen keywords were
      used to locate potentially relevant IPE statements within each accreditation
      document. Identified statements were independently categorized by each author
      into one of three mutually exclusive categories: accountable, non-accountable or
      non-applicable (kappa = 0.79; 95% CI 0.69-0.89). Eighteen of 21 accreditation
      documents analyzed contained applicable IPE statements. The Commission on
      Collegiate Nursing Education and Accreditation Council for Pharmacy Education
      documents contained 77% (46/60) of accountable IPE statements. Two-thirds (14/21)
      of documents contained two or fewer accountable IPE statements. Statement
      categorization using inductive methodology identified four IPE student competency
      and organizational structure/process domains, respectively. Collectively, US
      health professions' graduates are not required to complete IPE and, therefore,
      may not be prepared for IPCP. US accrediting bodies are encouraged to collaborate
      to create a common IPE accreditation standard.

PMID- 22950793
TI  - Abstracts of the Joint International Neurogastroenterology and Motility Meeting.
      September 6-8, 2012. Bologna, Italy.

PMID- 22950795
TI  - Abstracts of the Stillbirth Summit 2011. Minneapolis, Minnesota, USA. October 6
      8, 2011.

PMID- 22950796
TI  - Tunable cross coupling of silanols: selective synthesis of heavily substituted
      allenes and butadienes.
AB  - 1,3-Dienyl-2-silanols with a wide range of substitution patterns are readily
      obtained by palladium-catalyzed silaboration of 1,3-enynes followed by Suzuki
      Miyaura cross coupling with aryl bromides. Subsequent Hiyama-Denmark cross
      coupling with aryl iodides provides either 1,3- or 1,2-dienes in high yields. The
      site selectivity can be fully controlled by the choice of activator used in the
      coupling reaction. In the presence of strong bases such as NaOt-Bu, KOt-Bu, and
      NaH, clean formation of 1,2-dienes takes place via allylic rearrangement. In
      contrast, stereo- and site-selective formation of tetra- and trisubstituted 1,3
      dienes results from use of Ag(2)O and Bu(4)NF.3H(2)O, respectively, as
      activators. Under microwave heating at 100  degrees C the base-mediated cross
      couplings are largely accelerated and are completed within one hour or less. The
      ratio of diastereomeric allenes varies depending on the substitution pattern of
      the silanol and ranges from >99:1 to 52:48.

PMID- 22950794
TI  - Role of regulatory micro RNAs in type 2 diabetes mellitus-related inflammation.
AB  - Micro RNAs (miRNAs) are small, non-coding RNAs with the function of post
      transcriptional gene expression regulation. Micro RNAs may function in networks,
      forming a complex relationship with diseases. Alterations of specific miRNA
      levels have significant correlation with diseases of divergent origin, such as
      diabetes. Type 2 diabetes mellitus (T2DM) has an increasing worldwide epidemic
      with serious complications. However, T2DM is a chronic process, and from early
      metabolic alterations to manifest complications decades may pass, during which
      our diagnostic arsenal is limited. Micro RNAs may thus serve as novel diagnostic
      tools as well as therapeutic targets in pre-diabetes.   Recent Fundings: Micro
      RNAs (miRNAs) involved in inflammatory processes contributing to the development
      of type 2 diabetes mellitus (T2DM) published mostly in the past 2 years. MiRNAs
      are involved in such early diabetic processes as non-alcoholic steatohepatitis
      (NASH) and inflammation of the visceral adipose tissue. Evidence is emerging
      regarding the continuous spectrum between type 1 diabetes (T1DM) and T2DM being
      just 2 endpoints of the same disease with different genetic background. Thus,
      miRNA regulation of autoimmune components in T2DM may shed new light on
      pathogenesis. Finally, the involvement of miRNAs in inflammation as a key driving
      force of diabetic complications is also summarized. CONCLUSION: Inflammation is
      emerging as a central pathophysiological process in the development of T2DM.
      Visceral adipose tissue inflammation and non-alcoholic steatohepatitis together
      with insulitis are probably the first events leading to a complex metabolic
      disorder. These early events may be diagnosed or even influenced through our
      increasing knowledge about the involvement of post-transcriptional gene
      regulation by miRNAs.

PMID- 22950797
TI  - Characterization of a 65 kDa NIF in the nuclear matrix of the monocot Allium cepa
      that interacts with nuclear spectrin-like proteins.
AB  - Plant cells have a well organized nucleus and nuclear matrix, but lack
      orthologues of the main structural components of the metazoan nuclear matrix.
      Although data is limited, most plant nuclear structural proteins are coiled-coil
      proteins, such as the NIFs (nuclear intermediate filaments) in Pisum sativum that
      cross-react with anti-intermediate filament and anti-lamin antibodies, form
      filaments 6-12 nm in diameter in vitro, and may play the role of lamins. We have
      investigated the conservation and features of NIFs in a monocot species, Allium
      cepa, and compared them with onion lamin-like proteins. Polyclonal antisera
      against the pea 65 kDa NIF were used in 1D and 2D Western blots, ICM
      (imunofluorescence confocal microscopy) and IEM (immunoelectron microscopy).
      Their presence in the nuclear matrix was analysed by differential extraction of
      nuclei, and their association with structural spectrin-like proteins by co
      immunoprecipitation and co-localization in ICM. NIF is a conserved structural
      component of the nucleus and its matrix in monocots with Mr and pI values similar
      to those of pea 65 kDa NIF, which localized to the nuclear envelope,
      perichromatin domains and foci, and to the nuclear matrix, interacting directly
      with structural nuclear spectrin-like proteins. Its similarities with some of the
      proteins described as onion lamin-like proteins suggest that they are highly
      related or perhaps the same proteins.

PMID- 22950798
TI  - Conservation of gene order in human microRNA-neighboring regions.
AB  - The biological function and evolution of microRNAs (miRNAs), an important class
      of noncoding regulatory genes, have attracted wide interest. However, their
      evolutionary impact on gene order rearrangements remains unknown. We examined the
      gene-order stability of miRNA-neighboring regions by a comparative human-mouse
      genomic analysis and found that the neighboring genes of human miRNAs tend to
      have a conserved gene order. This observation cannot be attributed to the
      functional bias of neighboring genes, and is a unique characteristic of miRNAs
      but not other noncoding RNAs. Our findings suggest that mammalian miRNAs
      stabilize the genomic architecture in evolution.

PMID- 22950799
TI  - The prebiotic effect of Anoectochilus formosanus and its consequences on bone
      health.
AB  - The present study evaluated the prebiotic effect of a standardised aqueous
      extract of Anoectochilus formosanus (SAEAF) and its effects on osteoporosis in
      ovariectomised (OVX) rats. The OVX rats were randomly divided into five groups
      and orally treated with water, SAEAF (200 and 400 mg/kg daily) and inulin (400
      mg/kg daily) for 12 weeks. The sham group was orally treated with water. The
      SAEAF treatment enhanced the number of faecal bifidobacteria in OVX rats. The
      results of a Ca-balance experiment showed that SAEAF increased apparent Ca
      absorption and retention. The OVX rats were killed after SAEAF treatment lasting
      12 weeks. The SAEAF decreased the caecal pH values and increased the caecal wall
      weight, caecal mucosa calbindin-D9k mRNA expression, free-Ca concentration and
      levels of SCFA in the caecum. The mineral content, density and biomechanical
      strength of bones were lower in OVX rats than the sham group, but these bone
      losses were prevented by SAEAF administration. Microtomography scanning showed
      that the SAEAF-treated rats had higher trabecular bone volume than the OVX rats.
      These results suggest that SAEAF prevented bone loss associated with ovarian
      hormone deficiency in the rats.

PMID- 22950800
TI  - Nucleophilic reactivities of hydrazines and amines: the futile search for the
      alpha-effect in hydrazine reactivities.
AB  - The kinetics of the reactions of amines, hydrazines, hydrazides, and
      hydroxylamines with benzhydrylium ions and quinone methides were studied in
      acetonitrile and water by UV-vis spectroscopy, using conventional spectrometers
      and stopped-flow and laser-flash techniques. From the second-order rate constants
      k(2) of these reactions, the nucleophilicity parameters N and s(N) were
      determined according to the linear free energy relationship log k(2) = s(N)(N +
      E). While methyl groups increase the reactivities of the alpha-position of
      hydrazines, they decrease the reactivities of the beta-position. Despite the
      10(2) times lower reactivities of amines and hydrazines in water than in
      acetonitrile, the relative reactivities of differently substituted amines and
      hydrazines are almost identical in the two solvents. In both solvents hydrazine
      has a reactivity similar to that of methylamine. This observation implies that
      replacement of one hydrogen in ammonia by Me increases the nucleophilicity more
      than introduction of an amino group, if one takes into account that hydrazine has
      two reactive centers. Plots of log k(2) versus the corresponding equilibrium
      constants (log K) or Bronsted basicities (pK(aH)) do not show enhanced
      nucleophilicities (alpha-effect) for either hydrazines or hydroxylamine relative
      to alkylamines.

PMID- 22950801
TI  - TEMPO-oxidized nanocellulose participating as crosslinking aid for alginate-based
      sponges.
AB  - Crosslinked polysaccharide sponges have been prepared by freeze-drying of
      amorphous alginate-oxidized nanocellulose in the presence of a Ca(2+) ionic
      crosslinking agent. The new carboxyl groups on the surface of nanocellulose
      induced by the chemical oxidization provided the possibility of participating in
      the construction of an alginate-based sponge's structure and played a fundamental
      role in the structural and mechanical stability of ensuing sponges. Furthermore,
      enhanced mechanical strength induced by oxidized cellulose nanocrystals and the
      formation of a semi-interpenetrating polymer network from oxidized
      microfibrillated cellulose were reported. Together with the facile and ionic
      crosslinking process, the ultrahigh porosity, promising water absorption and
      retention, as well as the improved compression strength of the crosslinked
      sponges should significantly extend the use of this soft material in diverse
      practical applications.

PMID- 22950802
TI  - Controlling the localization of polymer-functionalized nanoparticles in mixed
      lipid/polymer membranes.
AB  - Surface hydrophobicity plays a significant role in controlling the interactions
      between nanoparticles and lipid membranes. In principle, a nanoparticle can be
      encapsulated into a liposome, either being incorporated into the hydrophobic
      bilayer interior or trapped within the aqueous vesicle core. In this paper, we
      demonstrate the preparation and characterization of polymer-functionalized CdSe
      NPs, tuning their interaction with mixed lipid/polymer membranes from 1,2
      dipalmitoyl-sn-glycero-3-phophocholine and PIB(87)-b-PEO(17) block copolymer by
      varying their surface hydrophobicity. It is observed that hydrophobic PIB
      modified CdSe NPs can be selectively located within polymer domains in a mixed
      lipid/polymer monolayer at the air/water interface, changing their typical domain
      morphologies, while amphiphilic PIB-PEO-modified CdSe NPs showed no specific
      localization in phase-separated lipid/polymer films. In addition, hydrophilic
      water-soluble CdSe NPs can readily adsorb onto spread monolayers, showing a
      larger effect on the molecule packing at the air/water interface in the case of
      pure lipid films compared to mixed monolayers. Furthermore, the incorporation of
      PIB-modified CdSe NPs into hybrid lipid/polymer GUVs is demonstrated with respect
      to the prevailing phase state of the hybrid membrane. Monitoring fluorescent
      labeled PIB-CdSe NPs embedded into phase-separated vesicles, it is demonstrated
      that they are enriched in one specific phase, thus probing their selective
      incorporation into the hydrophobic portion of PIB(87)-b-PEO(17) BCP-rich domains.
      Thus, the formation of biocompatible hybrid GUVs with selectively incorporated
      nanoparticles opens a new perspective for subtle engineering of membranes
      together with their (nano-) phase structure serving as a model system in
      designing functional nanomaterials for effective nanomedicine or drug delivery.

PMID- 22950803
TI  - A coordination chemistry study of hydrated and solvated cationic vanadium ions in
      oxidation states +III, +IV, and +V in solution and solid state.
AB  - The coordination chemistry of hydrated and solvated vanadium(III),
      oxovanadium(IV), and dioxovanadium(V) ions in the oxygen-donor solvents water,
      dimethyl sulfoxide (DMSO), and N,N'-dimethylpropyleneurea (DMPU) has been studied
      in solution by extended X-ray absorption fine structure (EXAFS) and large-angle X
      ray scattering (LAXS) and in the solid state by single-crystal X-ray diffraction
      and EXAFS. The hydrated vanadium(III) ion has a regular octahedral configuration
      with a mean V-O bond distance of 1.99 A. In the hydrated and DMSO-solvated
      oxovanadium(IV) ions, vanadium binds strongly to an oxo group at ca. 1.6 A. The
      solvent molecule trans to the oxo group is very weakly bound, at ca. 2.2 A, while
      the remaining four solvent molecules, with a mean V-O bond distance of 2.0 A,
      form a plane slightly below the vanadium atom; the mean O?V-O(perp) bond angle is
      ca. 98 degrees . In the DMPU-solvated oxovanadium(IV) ion, the space-demanding
      properties of the DMPU molecule leave no solvent molecule in the trans position
      to the oxo group, which reduces the coordination number to 5. The O?V-O bond
      angle is consequently much larger, 107 degrees , and the mean V?O and V-O bond
      distances decrease to 1.58 and 1.97 A, respectively. The hydrated and DMSO
      solvated dioxovanadium(V) ions display a very distorted octahedral configuration
      with the oxo groups in the cis position with a mean V?O bond distance of 1.6 A
      and a O?V?O bond angle of ca. 105 degrees . The solvent molecules trans to the
      oxo groups are weakly bound, at ca. 2.2 A, while the remaining two have bond
      distances of 2.02 A. The experimental studies of the coordination chemistry of
      hydrated and solvated vanadium(III,IV,V) ions are complemented by summarizing
      previously reported crystal structures to yield a comprehensive description of
      the coordination chemistry of vanadium with oxygen-donor ligands.

PMID- 22950804
TI  - Serial and parallel processing in reading: investigating the effects of
      parafoveal orthographic information on nonisolated word recognition.
AB  - We present a novel lexical decision task and three boundary paradigm eye-tracking
      experiments that clarify the picture of parallel processing in word recognition
      in context. First, we show that lexical decision is facilitated by associated
      letter information to the left and right of the word, with no apparent
      hemispheric specificity. Second, we show that parafoveal preview of a repeat of
      word n at word n + 1 facilitates reading of word n relative to a control
      condition with an unrelated word at word n + 1. Third, using a version of the
      boundary paradigm that allowed for a regressive eye movement, we show no
      parafoveal "postview" effect on reading word n of repeating word n at word n - 1.
      Fourth, we repeat the second experiment but compare the effects of parafoveal
      previews consisting of a repeated word n with a transposed central bigram (e.g.,
      caot for coat) and a substituted central bigram (e.g., ceit for coat), showing
      the latter to have a deleterious effect on processing word n, thereby
      demonstrating that the parafoveal preview effect is at least orthographic and not
      purely visual.

PMID- 22950805
TI  - Sustaining cardiovascular absolute risk management in Australian general
      practice.
AB  - This study describes the attitudes and practices of patients and GPs 12 months
      after participating in a trial of absolute cardiovascular risk assessment in
      general practice. It involved a qualitative design using semistructured
      interviews with 12 Sydney GPs from the intervention arm of a cluster randomised
      controlled trial of cardiovascular absolute risk (CVAR) assessment and 15 of
      their moderate to high risk patients who participated in the assessments. Most
      GPs had sustained CVAR assessment in their practice, using it primarily to
      motivate patients to change their behaviour and adhere to management rather than
      to make decisions about pharmacotherapy or referral. Time was a barrier to its
      use. Patients who sustained changes to their behaviour had internalised the
      benefits to their health and received support from family and friends. Those who
      relapsed attributed this to their own lack of motivation and extrinsic factors.
      CVAR assessment needs to be incorporated into practice information systems and
      long-term planned preventive care if it is to be sustained in general practice
      and have long-term impacts on patient behaviour.

PMID- 22950806
TI  - Development of an eight-subtest short form of the WISC-IV and evaluation of its
      clinical utility in children with traumatic brain injury.
AB  - This study evaluated the degree to which an 8-subtest short form of the Wechsler
      Intelligence Scale for Children--Fourth Edition would yield acceptable estimates
      of the long-form Full-Scale IQ index while clarifying the underlying factor
      structure in a sample of 100 children and adolescents with traumatic brain
      injury. The short-form Full-Scale IQ had sufficient (i.e., at least two thirds)
      nonerror covariance with its full-length counterpart. In addition, a sufficient
      proportion (i.e., > 80%) of these short-form estimates fell within the 90%
      confidence interval of the respective full-length scores. Importantly, the
      elimination of 2 subtests, and in particular the Picture Concepts subtest,
      resulted in a factor structure where each remaining subtest was fairly
      specifically associated with its intended scale. It is concluded that this short
      form can be used clinically in children with traumatic brain injury without
      sacrificing reliability and with more straightforward interpretability at the
      level of the factor index scores.

PMID- 22950807
TI  - Effect of a public awareness campaign on the incidence of symptomatic objectively
      confirmed deep vein thrombosis: a controlled study.
AB  - BACKGROUND: Although there have been attempts to raise public awareness about
      deep vein thrombosis (DVT), their influence on identifying confirmed cases is
      unknown. OBJECTIVE: To determine the effect and its duration of a public
      awareness campaign about venous thromboembolism. PATIENTS/METHODS: A campaign to
      raise public awareness of DVT was conducted during one year in an urban
      population of approximately 100,000 (pop A). A comparison urban population of
      approximately 1,574,000 (pop B) was not exposed to this campaign. Patients
      symptomatic for DVT in both populations were referred by general practitioners
      for a standardized compression ultrasound (CUS) of the whole leg at no charge.
      Positive CUS examinations documented by photographs were analyzed by an
      independent adjudication committee blinded to the population. Pop A was followed
      for 8 months after the information campaign ended. RESULTS AND CONCLUSIONS:  
      Symptomatic objectively confirmed DVT was found in 48 of 800 subjects tested in
      pop A and 226 of 2384 tested in pop B. The 1-year incidence of confirmed DVT
      (proximal and distal) was 46/100,000 (95% CI, 33-59) in A and 14/100,000 (95% CI,
      12-16) in B (P < 0.001). The increase in pop A was due to distal DVT (36/100,000
      vs. 5/100,000 in pop B, P < 0.001). The DVT rate for pop A in an 8-month follow
      up period was 12/100,000, significantly lower than in the first 8 months of the
      study period (34/100,000/8 months) (P = 0.001). The public awareness campaign
      significantly increased the diagnosis of distal DVT. When the campaign ended, DVT
      rates returned to community baseline.

PMID- 22950809
TI  - The state of risk prevention in a sample of Australian hospitals, medical centres
      and allied health services.
AB  - This paper reports on an investigation into five risk prevention factors
      (technology, people, organisational structure, culture and top management
      psychology) to inform organisational preparedness planning and to update managers
      on the state of health care services. Data were collected by means of a 10
      question, cross-sectional survey of key decision-making executives in eight
      different types of 75 health care organisations. Many organisations were found to
      have deficient risk prevention practices and allied health organisations were
      considerably worse than health organisations. Forty per cent of hospitals and
      chiropractic practices had out-dated or poor technology. Results on
      organisational culture and structure found that many executives associate these
      factors with risk prevention, but none of them appreciate the relationship
      between these factors and crisis causation. Gaps and areas for improvement are
      identified and a change in top management attitude is recommended to address
      resource allocation and implement appropriate risk prevention systems and
      mechanisms. Reactive managers need to increase their awareness of risks in order
      to become capable of preventing them. Proactive managers are those who invest in
      risk prevention. 

PMID- 22950808
TI  - Elevated C-peptide and insulin predict increased risk of colorectal adenomas in
      normal mucosa.
AB  - BACKGROUND: Lower concentrations of the insulin-like growth factor binding
      protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been
      associated with an increase in colorectal cancer risk (CRC). However few studies
      have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only
      known precursor for CRC. METHODS: Between November 2001 and December 2002, we
      examined associations between circulating concentrations of insulin, C-peptide,
      IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps
      and 488 with no adenomatous polyps using logistic regression models. RESULTS:
      Individuals with the highest concentrations of C-peptide were more likely to have
      adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations;
      associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than
      women. Individuals with high insulin concentrations also had a higher risk of
      adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were
      associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1
      0.7). Overweight and obese individuals with higher C-peptide levels (>1(st) Q)
      were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an
      association that remained strong in overweight and obese men (OR = 6.3, 95% CI
      1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were
      associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0).
      CONCLUSIONS: Associations between these peptides and the apoptosis index in
      overweight and obese individuals, suggest that the mechanism by which C-peptide
      could induce adenomas may include its anti-apoptotic properties. This study
      suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that
      outcomes associated with colorectal carcinogenesis maybe modified by gender.

PMID- 22950810
TI  - Composite microspheres for separation of plasmid DNA decorated with MNPs through
      in situ growth or interfacial immobilization followed by silica coating.
AB  - Raspberry-like colloidal polymer/magnetite/silica composite microspheres were
      rationally fabricated based on in situ growth or interfacial immobilization of
      magnetic nanoparticles (MNPs) onto the polymer matrices and the followed sol-gel
      coating process. Monodisperse cross-linked poly(styrene-co-glycidyl methacrylate)
      microspheres were first prepared by surfactant-free emulsion polymerization,
      followed by surface modification of carboxyl or amine moieties through thiol
      epoxy click chemistry. Then the carboxyl-modified microspheres were in situ
      decorated with MNPs through solvothermal process or chemical coprecipitation
      reaction. In parallel, incorporation of MNPs onto polymer matrices was also
      realized by the interaction of amine-modified polymer microspheres with carboxyl
      capped MNPs based on the electrostatic interaction. The two pathways for
      synthesis of the composite microspheres decorated with MNPs were systematically
      investigated. Furthermore, the composite microspheres were coated with a thin
      layer of silica through a sol-gel process. The thus-produced magnetic composite
      microspheres with desirable magnetization (~23 emu/g) served as effective
      supports for high-payload plasmid DNA enrichment (~17 MUg per mg of
      microspheres), much better than that of the commercial-available sample of SM1
      015B (~12 MUg per mg of SM1-015B), shedding lights on the potential advantages of
      the nanoplatforms for separation of bioactive entities.

PMID- 22950811
TI  - DNA origami delivery system for cancer therapy with tunable release properties.
AB  - In the assembly of DNA nanostructures, the specificity of Watson-Crick base
      pairing is used to control matter at the nanoscale. Using this technology for
      drug delivery is a promising route toward the magic bullet concept, as it would
      allow the realization of complex assemblies that co-localize drugs, targeting
      ligands and other functionalities in one nanostructure. Anthracyclines' mechanism
      of action in cancer therapy is to intercalate DNA, and since DNA nanotechnology
      allows for such a high degree of customization, we hypothesized that this would
      allow us to tune the DNA nanostructures for optimal delivery of the anthracycline
      doxorubicin (Dox) to human breast cancer cells. We have tested two DNA origami
      nanostructures on three different breast cancer cell lines (MDA-MB-231, MDA-MB
      468, and MCF-7). The different nanostructures were designed to exhibit varying
      degrees of global twist, leading to different amounts of relaxation in the DNA
      double-helix structure. By tuning the nanostructure design we are able to (i)
      tune the encapsulation efficiency and the release rate of the drug and (ii)
      increase the cytotoxicity and lower the intracellular elimination rate when
      compared to free Dox. Enhanced apoptosis induced by the delivery system in breast
      cancer cells was investigated using flow cytometry. The findings indicate that
      DNA origami nanostructures represent an efficient delivery system for Dox,
      resulting in high degrees of internalization and increased induction of
      programmed cell death in breast cancer cells. In addition, by designing the
      structures to exhibit different degrees of twist, we are able to rationally
      control and tailor the drug release kinetics.

PMID- 22950812
TI  - Cascading radical cyclization of bis-vinyl ethers: mechanistic investigation
      reveals a 5-exo/3-exo/retro-3-exo/5-exo pathway.
AB  - We recently described an iterative synthesis of oligo-vinyl ethers, followed by a
      radical cascade to provide a family of hexahydro-2H-furo[3,4-b]pyrans. Our
      results for the radical cascade were consistent with either a direct 6-endo-trig
      addition of a vinyl radical onto the first vinyl ether function or an initial 5
      exo-trig addition, followed by rearrangement to the more stable anomeric radical
      intermediate. In this report, we describe our further mechanistic studies aimed
      at distinguishing between these two possibilities and conclude that the 5-exo/3
      exo/retro-3-exo pathway is dominant.

PMID- 22950814
TI  - New kaurene diterpenoid glycosides from fenugreek seeds.
AB  - Two new kaurene diterpenoid glycosides, named Graecumoside A (1) and B (2), were
      isolated from fenugreek seeds, along with three known flavonoid-C-glycosides,
      isoorientin (3), isovitexin (4) and vitexin (5). By combined analyses of 1D- and
      2D-NMR, and MS spectroscopy, the structures of two new compounds were elucidated
      as 3-O-beta- D-glucopyranosyl kaur-5, 16-dien-3beta, 6, 13beta-trihydroxy-7-oxo
      18-oic acid methyl ester and 3-O-beta-neohesperidosyl kaur-5, 16-dien-3beta, 6,
      13beta-trihydroxy-7-oxo-18-oic acid methyl ester, respectively. The kaurene
      diterpenoid glycosides were first isolated and identified from fenugreek seeds. 

PMID- 22950813
TI  - Inflammation induced by lipopolysaccharide does not prevent the vitamin A and
      retinoic acid-induced increase in retinyl ester formation in neonatal rat lungs.
AB  - Vitamin A (VA) plays an important role in post-natal lung development and
      maturation. Previously, we have reported that a supplemental dose of VA combined
      with 10% of all-trans-retinoic acid (VARA) synergistically increases retinol
      uptake and retinyl ester (RE) storage in neonatal rat lung, while up-regulating
      several retinoid homeostatic genes including lecithin:retinol acyltransferase
      (LRAT) and the retinol-binding protein receptor, stimulated by retinoic acid 6
      (STRA6). However, whether inflammation has an impact on the expression of these
      genes and thus compromises the ability of VARA to increase lung RE content is not
      clear. Neonatal rats, 7- to 8-d-old, were treated with VARA either concurrently
      with lipopolysaccharide (LPS; Expt 1) or 12 h after LPS administration (Expt 2);
      in both studies, lung tissue was collected 6 h after VARA treatment, when RE
      formation is maximal. Inflammation was confirmed by increased IL-6 and chemokine
      (C-C motif) ligand 2 (CCL2) gene expression in lung at 6 h and C-reactive protein
      in plasma at 18 h. In both studies, LPS-induced inflammation only slightly
      reduced, but did not prevent the VARA-induced increase in lung RE. Quantitative
      RT-PCR showed that co-administration of LPS with VARA slightly attenuated the
      VARA-induced increase of LRAT mRNA, but not of STRA6 or cytochrome P450 26B1, the
      predominant RA hydroxylase in lung. By 18 h post-LPS, expression had subsided and
      none of these genes differed from the level in the control group. Overall, the
      present results suggest that retinoid homeostatic gene expression is reduced
      modestly, if at all, by acute LPS-induced inflammation and that VARA is still
      effective in increasing lung RE under conditions of moderate inflammation.

PMID- 22950815
TI  - Reductive deprotonation and dehydrogenation of phenylhydrazine at a nickel center
      to give a nickel diazenido complex.
AB  - The reaction of [L(tBu)Ni(OEt(2))] (where L(tBu) =
      [HC(C(t)BuNC(6)H(3)((i)Pr)(2))(2)](-)) with phenylhydrazine leads to the
      phenylhydrazido(1-) complex [L(tBu)Ni(eta(2)-NPhNH(2))] (1) with concomitant
      formation of H(2). Treatment of 1 with potassium graphite in the presence of
      crown ether again leads to H(2) evolution and affords the heterobimetallic
      complex [L(tBu)Ni(MU-eta(2):eta(2)-NPhNH)]K(18-crown-6) containing the doubly
      deprotonated phenylhydrazido(2-) ligand. 1 can be converted into a
      phenyldiazenido complex [L(tBu)Ni(eta(1)-NNPh)] in the course of a
      dehydrogenation reaction employing 1,2-diisopropylazo dicarboxylate (DIAD) as the
      oxidant.

PMID- 22950816
TI  - Effect of acupuncture therapy for postponing Wallerian degeneration of cerebral
      infarction as shown by diffusion tensor imaging.
AB  - OBJECTIVE: One aim of this study was to investigate the effects of acupuncture on
      cerebral function of patients with acute cerebral infarction. Another goal was to
      evaluate the relationship between acupuncture treatment and motor recovery
      patients with stroke and to provide a foundation for using acupuncture therapy
      for such patients. DESIGN: Twenty (20) patients with recent cerebral infarction
      were divided randomly to an acupuncture group and a control group. The infarction
      area in each patient was in the basal ganglia or included the basal ganglia with
      an area size of > 1 cm(2). Serial diffusion tensor imaging (DTI), fluid
      attenuated inversion recovery (FLAIR), and T2-weighted imaging (T(2)WI) scans
      were performed on all patients and the results were evaluated using the National
      Institute of Health Stroke Scale and the Barthel Index each week. DTI images were
      postprocessed and analyzed. Apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) values of abnormal signals on DTI in the infarction areas and
      cerebral peduncles were calculated for both groups and compared with one another.
      RESULTS: (1) The ADC value of infarction lesions decreased at stroke onset; then,
      a significant elevation was observed after the acute stage, and a significant
      reduction in FA values was observed from stroke onset to the chronic stage. (2)
      The ADC of the bilateral cerebral peduncle was reduced on the infarction side.
      (3) There was a significant difference in ADC and FA values between the
      acupuncture and control groups. The FA value was higher in the acupuncture group
      than the control group. CONCLUSIONS: ADC and FA values might correlate to patient
      recovery and reveal the progress of secondary degeneration. Acupuncture treatment
      is effective for protecting neurons and facilitating recovery.

PMID- 22950817
TI  - Volatiles from apple trees infested with light brown apple moth larvae attract
      the parasitoid Dolichogenidia tasmanica.
AB  - The volatile compounds emitted from uninfested apple seedlings, cv. Royal Gala,
      and apple seedlings infested with generalist herbivore  Epiphyas postvittana 
      larvae were sampled using headspace collection and analyzed by gas chromatography
      mass spectrometry. Nine additional compounds were only detected in infested apple
      seedlings [including benzyl alcohol, (E)-beta-ocimene, benzyl cyanide, indole,
      (E)-nerolidol, and four unidentified compounds]. Infested apple seedlings
      produced larger amounts of (Z)-3-hexenyl acetate, linalool, 4,8-dimethyl-1,3(E),7
      nonatriene, methyl salicylate, beta-caryophyllene, germacrene D, (E,E)-alpha
      farnesene, and (Z)-3-hexenyl benzoate than uninfested plants. Female parasitoids
      flew exclusively upwind to infested and not to uninfested apple seedlings in wind
      tunnel choice tests and preferred infested leaflets in still air, even after the
      removal of larvae. The attraction of a parasitoid to infested apple seedlings in
      the laboratory and in the field to apple and many other plants in at least six
      families supports considerable generality of the tritrophic signaling process.

PMID- 22950818
TI  - Waldenstrom's macroglobulinemia-associated renal amyloidosis presenting as a
      solitary lung mass.
AB  - A single nodular lesion can be observed in various pulmonary diseases, including
      cancer, tuberculosis, and fungal infection. Waldenstrom's macroglobulinemia (WM)
      usually occurs in older adults and involves the lymph nodes, bone marrow, and
      spleen. Respiratory tract involvement is very rare. We reported a case of WM
      associated renal amyloidosis. The patient was admitted with the initial
      presentation as a single mass in the lung and progression to renal involvement.

PMID- 22950819
TI  - Expression of cyclin A, B1 and D1 after induction of cell cycle arrest in the
      Jurkat cell line exposed to doxorubicin.
AB  - Jurkat human lymphoblastoid cells were incubated in increasing concentrations of
      doxorubicin (0.05, 0.1 and 0.15 MUM) to induce cell death, and their expression
      of cyclin A, B1 and D1 was evaluated by flow cytometry (cell cycle progression,
      Annexin V assay, percentages and levels of each of the cyclins), transmission
      electron microscopy (ultrastructure) and confocal fluorescence microscopy
      (expression and intracellular localization of cyclins). After low-dose
      doxorubicin treatment, Jurkat cells responded mainly by G2/M arrest, which was
      related to increased cyclin B1, A and D1 levels, a low level of apoptosis and/or
      mitotic catastrophe. The influence of doxorubicin on levels and/or localization
      of selected cyclins was confirmed, which may in turn contribute to the G2/M
      arrest induced by the drug.

PMID- 22950820
TI  - Methods for culturing saltwater rotifers (Brachionus plicatilis) for rearing
      larval zebrafish.
AB  - The saltwater rotifer, Brachionus plicatilis, is widely used in the aquaculture
      industry as a prey item for first-feeding fishes due to its ease of culture,
      small size, rapid reproductive rate, and amenability to enrichment with
      nutrients. Despite the distinct advantages of this approach, rotifers have only
      been sporadically utilized for rearing larval zebrafish, primarily because of the
      common misconception that maintaining cultures of rotifers is difficult and
      excessively time-consuming. Here we present simple methods for maintaining
      continuous cultures of rotifers capable of supporting even the very largest
      zebrafish aquaculture facility, with minimal investments in materials, time,
      labor, and space. Examples of the methods' application in one large, existing
      facility is provided, and troubleshooting of common problems is discussed.

PMID- 22950821
TI  - Reinvestigation of the photocatalytic reaction mechanism for Pt-complex-modified
      TiO2 under visible light irradiation by means of ESR spectroscopy and
      chemiluminescence photometry.
AB  - A plausible reaction mechanism for a visible light photocatalyst of TiO(2)
      modified with platinum(IV) chloride (PtCl) was proposed on the basis of the
      measurements with electron spin resonance (ESR) spectroscopy and
      chemiluminescence photometry. Under visible light (lambda > 500 nm) irradiation,
      the deposited Pt(IV) chloride is charge-separated into Pt(3+) and Cl radical by
      the excitation of the ligand-to-metal charge transfer. The Pt(3+) gives an
      electron to the conduction band of TiO(2), which has Pt(3+) return to Pt(4+). The
      electron in the conduction band reduces the oxygen molecule into O(2)(-). The
      presence of Pt(3+) and O(2)(-) has been elucidated in the present study.
      Moreover, valence band holes of TiO(2) were detected by ESR spectroscopy under
      visible light irradiation. Therefore, besides being used to oxidize organic
      compounds, the photogenerated Cl radicals likely receive electrons from the
      TiO(2) valence band by visible light excitation, producing the valence band
      holes. Because the valence band holes have a stronger oxidation power than Cl
      radicals, the excitation of valence band electrons to Cl radicals would be the
      origin of the high photocatalytic activity of the PtCl-modified TiO(2) under
      visible light irradiation.

PMID- 22950822
TI  - Conformation of single polymer chain in rubbed thin film observed by fluorescence
      imaging.
AB  - The conformation of poly(methyl methacrylate) (PMMA) chains in a thin film after
      the rubbing process was investigated through the direct observation of the single
      chains by scanning near-field optical microscopy (SNOM) and excitation
      polarization modulation microscopy (EPMM). The rubbing at room temperature hardly
      changed the dimension on the whole chain scale in spite of the increase in
      orientational order on the segmental scale. The increase in the chain dimension
      along the rubbing direction was observed in the film rubbed at the higher
      temperature, which showed a surface morphology with fine groove. The extension
      ratio of the whole chain in the rubbed film was much smaller than that in the
      uniaxially stretched film. This indicates that the rubbing process mainly induces
      the conformational change on the length scale of the monomer unit rather than for
      the whole chain.

PMID- 22950823
TI  - Activating patients with chronic disease for self-management: comparison of self
      managing patients with those managing by frequent readmissions to hospital.
AB  - Understanding the factors that activate people to self-manage chronic disease is
      important in improving uptake levels. If the many frequent hospital users who
      present with acute exacerbations of chronic disease were to self-manage at home,
      some hospital admissions would be avoided. Patient interview and demographic,
      psychological, clinical and service utilisation data were compared for two groups
      of patients with chronic disease: those attending self-management services and
      those who managed by using hospital services. Data were analysed to see whether
      there were differences that might explain the two different approaches to
      managing their conditions. The two groups were similar in terms of comorbidity,
      age, sex, home services, home support and educational level. Self-managing
      patients were activated by their clinician, accepted their disease, changed their
      identity, confronted emotions and learnt the skills to self-manage and avoid
      hospital. Patients who frequently used hospital services to manage their chronic
      disease were often in denial about their chronic disease, hung on to their
      identity and expressed little emotional response. However, they reported a
      stronger sense of coherence and rated their health more highly than self-managing
      patients. This study shed light on the process of patient activation for self
      management. A better understanding of the process of patient activation would
      encourage clinicians who come into contact with frequently readmitted chronic
      disease patients to be more proactive in supporting self-management. 

PMID- 22950824
TI  - The gut chooses faster than the mind: a latency advantage of affective over
      cognitive decisions.
AB  - Dual-process theories often cite that affective processing occurs more rapidly
      than cognitive processing. A wide range of evidence seems to support this notion;
      however, little research exists in the context of decision making. We tested the
      hypothesis that affective decisions would be performed faster than cognitive
      decisions. Forty-nine students completed a series of forced-choice tasks
      involving well-known consumer brands, focusing on either emotionally or
      cognitively relevant aspects of the products. The results revealed a significant
      latency advantage for affective processing compared to cognitive processing.

PMID- 22950825
TI  - Clinical, in silico, and experimental evidence for pathogenicity of two novel
      splice site mutations in the SH3TC2 gene.
AB  - Charcot-Marie-Tooth (CMT) neuropathy is the most common inherited neuromuscular
      disorder. CMT is genetically very heterogeneous. Mutations in the SH3TC2 gene
      cause Charcot-Marie-Tooth neuropathy type 4C (CMT4C), a demyelinating form with
      autosomal recessive inheritance. In this study, two novel splice site mutations
      in the SH3TC2 gene have been studied (c.279G -> A, c.3676-8G -> A). Mutation
      c.279G -> A was detected on one allele in two unrelated families with CMT4C in
      combination with a known pathogenic mutation (c.2860 C ->T in one family, c.505T 
      > C in the other) on the second allele of SH3TC2 gene. Variant c.3676-8G -> A was
      detected in two patients from unrelated families on one allele of the SH3TC2 gene
      in combination with c.2860C ->T mutation on the other allele. Several in silico
      tests were performed and exon trap experiments were undertaken in order to prove
      the effect of both mutations on proper splicing of SH3TC2. Fragments of SH3TC2
      were subcloned into pET01 exon trap vector (Mobitec) and transfected into COS-7
      cells. Aberrant splicing was predicted in silico for both mutations, which was
      confirmed by exon trap analysis. For c.279G -> A mutation, 19 bases from intron 3
      are retained in cDNA. The mutation c.3676-8G-> A produces a novel splice acceptor
      site for exon 17 and complex changes in splicing were observed. We present
      evidence that mutations c.279G -> A and c.3676-8G ->A in the SH3TC2 gene cause
      aberrant splicing and are therefore pathogenic and causal for CMT4C.

PMID- 22950827
TI  - Factors contributing to the sustainability of alcohol and other drug
      interventions in Australian community health settings.
AB  - This study identifies factors that support the sustainability of interventions
      implemented to enhance responses to alcohol and other drug misuse in Australian
      community health settings. Eight completed projects that had received time
      limited funding were sampled to reflect a mix of project types, contexts and
      success in meeting funding objectives. Projects were investigated using a case
      study approach involving thematic analysis. Project records were analysed and
      interviews were conducted with stakeholders to identify intervention elements
      that continued after funding ceased, and factors that supported this
      sustainability. Key factors identified were: embedding changes in the operations
      of the agency; filling a critical gap in the sector; building support from key
      individuals and agencies; and planning realistically for future ownership. We
      argue that complexity theory provides a framework to understand both the context
      bound nature of intervention sustainability and differences within the literature
      as to how sustainability is typologised. Each factor associated with intervention
      sustainability identified in this study reflects an astute understanding of
      project context and a capacity to adapt. These factors could assist people
      designing interventions with time-limited funding to maximise ongoing impact of
      interventions. They should optimally be implemented within an overall approach of
      flexibility and sensitivity to context.

PMID- 22950826
TI  - Quality of life across chemotherapy lines in patients with cancers of the
      pancreas and biliary tract.
AB  - BACKGROUND: In patients with cancers of the pancreatic and biliary tract quality
      of life (QOL) improvement is the main treatment goal, since survival can be
      prolonged only marginally. Up to date, knowledge on QOL impairments throughout
      the entire treatment process, often including several chemotherapy lines, is
      scarce. Our study aimed at investigating QOL trajectories from adjuvant treatment
      to palliative 3rd-line therapy METHODS: Patients were included in routine
      electronic patient-reported outcome monitoring at Kufstein County Hospital at the
      time of diagnosis and assessed with the EORTC QLQ-C30 during each chemotherapy
      cycle. RESULTS: Eighty out of 147 patients with pancreatic cancer or cancer of
      the bile ducts treated at the Kufstein County Hospital, fulfilled inclusion
      criteria and could be included in the study (mean age 67.4 years; 53.8% women).
      Physical, Emotional and Cognitive Functioning, and Global QOL deteriorated across
      chemotherapy lines, whereas Fatigue, Pain, Dyspnoea, Sleeping Disturbances,
      Diarrhoea, and Taste Alterations increased. With regard to Physical Functioning,
      Global QOL, Fatigue, Dyspnoea, Diarrhoea and Taste Alterations, the patients
      receiving adjuvant or 1st-line palliative chemotherapy did not differ
      significantly. Most patients in 2nd- or 3rd-line chemotherapy showed
      significantly higher impairments and symptom burden. However, patients under 1st
      and 2nd-line treatment showed stable QOL trajectories, whereas 3rd-line patients
      perceived substantial deteriorations. CONCLUSIONS: The results suggest early
      palliative treatment initiation to stabilise QOL on a level as high as possible.
      The continuous QOL improvement during adjuvant treatment, probably reflecting
      post-operative recovery, may indicate that deleterious effects of adjuvant
      chemotherapy on QOL are highly unlikely.

PMID- 22950828
TI  - Evaluating a healthy eating, healthy action program in small Maori communities in
      Aotearoa, New Zealand.
AB  - Evidence from health surveys have identified that Maori, the indigenous people of
      Aotearoa New Zealand, experience a high incidence of obesity with physical and
      social implications. In 2000, the New Zealand Government introduced a strategy
      aimed, among other objectives, at improving nutrition, increasing physical
      activity and reducing obesity through a 'Healthy Eating Health Action' (HEHA)
      strategy. As part of the HEHA strategy, a Maori primary health organisation (PHO)
      in a regional centre of Aotearoa, New Zealand, developed a program aimed at
      improving the health of the local Maori communities. The program, called Project
      REPLACE, invited participants to gradually change their behaviour by replacing
      behaviours potentially detrimental to health with a healthier alternative.
      Between 2009 and 2010 a team of researchers evaluated the program, taking care to
      use Maori approaches when conducting the research. The findings from the
      evaluation were that each community was innovative in their approaches to
      implementing Project REPLACE, drawing on their culture to combine healthy eating
      with increased exercise activities as well as measurements of achievement. The
      relationship that each coordinator had with the community was pivotal to the
      success of the program. Project REPLACE highlighted the importance of Maori
      ownership and control of health initiatives.

PMID- 22950829
TI  - P6 acupressure effectiveness on acute vertiginous patients: a double blind
      randomized study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of P6
      acupressure on vertigo and neurovegetative symptoms, its possible interference
      with vestibular-ocular reflex (VOR), and its clinical usefulness during acute
      vertigo. MATERIALS AND METHODS: Two hundred and four patients, either affected by
      acute vertigo (n=124) or undergoing labyrinth stimulation (n=80), were randomly
      divided in two homogeneous groups: an experimental group A and a placebo group B.
      Each patient rated severity of vertigo and neurovegetative symptoms on a visuo
      analogue scale ranging from 0 to 10, before and after bilateral placement of a P6
      device. The latter was placed on the P6 acupressure point (appropriate placement)
      in Group A patients or on the dorsal part of the carpus (inappropriate placement)
      in the Group B patients. Furthermore, qualitative and quantitative nystagmus
      parameters were collected via recorded video-oculoscopy and
      electronystagmography. RESULTS: Eighty-five percent of Group A patients reported
      improvement of symptoms, which was significant for neurovegetative symptoms, but
      not for vertigo. In contrast, only 11% of the Group B patients reported
      improvement. VOR analysis did not show any significant variation of qualitative
      and quantitative nystagmus variables. CONCLUSIONS: This study demonstrated that
      the P6 device is effective in improving neurovegetative symptoms in patients
      affected by spontaneous and provoked vertigo, without any interference with VOR.
      Given the low cost and lack of side-effects of the P6 device, its routine
      application is suggested for acute vertigo and during labyrinth stimulation.

PMID- 22950830
TI  - Direct deposition of cubic boron nitride films on tungsten carbide-cobalt.
AB  - Thick cubic boron nitride (cBN) films in micrometer-scale are deposited on
      tungsten carbide-cobalt (WC-Co) substrates without adhesion interlayers by
      inductively coupled plasma-enhanced chemical vapor deposition (ICP-CVD) using the
      chemistry of fluorine. The residual film stress is reduced because of very low
      ion-impact energies (a few eV to ~25 eV) controlled by the plasma sheath
      potential. Two types of substrate pretreatment are used successively; the removal
      of surface Co binder using an acid solution suppresses the catalytic effect of Co
      and triggers cBN formation, and the surface roughening using mechanical
      scratching and hydrogen plasma etching increases both the in-depth cBN fraction
      and deposition rate. The substrate surface condition is evaluated by the
      wettability of the probe liquids with different polarities and quantified by the
      apparent surface free energy calculated from the contact angle. The surface
      roughening enhances the compatibility in energy between the cBN and substrate,
      which are bridged by the interfacial sp(2)-bonded hexagonal BN buffer layer, and
      then, the cBN overlayer is nucleated and  evolved easier.

PMID- 22950831
TI  - Structural impact of platinum on the incommensurably modulated gamma-brass
      related composite structure Pd15Zn54.
AB  - The crystal structure of three incommensurately modulated gamma-brass related
      composite structures in the Pd-Zn-Pt system has been solved from X-ray single
      crystal diffraction data using a 3 + 1-dimensional super space description. The
      compounds Pt(x)Pd(15-x)Zn(54) (x ~ 6, 7, 10) crystallize in orthorhombic
      superspace group Fmmm(alpha00)0s0 (F = [(1/2, 1/2, 0, 0); (1/2, 0, 1/2, 0); (0,
      1/2, 1/2, 0)] with the following fundamental cell dimensions: a = 4.265(1) A, b =
      9.132(1) A, c = 12.928(2) A, q ~ 0.629a*; a = 4.284(1) A, b = 9.151(2) A, c =
      12.948(4) A, q ~ 0.628a*; and a = 4.288(1) A, b = 9.140(4) A, c = 12.926(7) A, q
      ~ 0.627a*. Each structure is built by two sub-lattices-pentagonal antiprismatic
      columns parallel to [100] and a zigzag chain of Zn atoms running along the center
      of the column.

PMID- 22950832
TI  - Aerobic palladium(II)-catalyzed dehydrogenation of cyclohexene-1-carbonyl indole
      amides: an indole-directed aromatization.
AB  - A palladium(II)-catalyzed oxidative dehydrogenation of cyclohexene-1-carbonyl
      indole amides yielding the corresponding benzoylindoles is reported. The new
      aromatization is also applied to functionalized indoles such as tryptamine and
      tryptophan. The tethered indole is likely acting as a directing group for allylic
      C-H bond activation, and there is evidence for a mechanism proceeding through 1,3
      diene formation followed by aromatization.

PMID- 22950833
TI  - Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary
      hemorrhage in the course of pulmonary tuberculosis.
AB  - A 66-year-old man with uremia and on hemodialysis was referred to our hospital
      because of hemoptysis. A chest radiograph showed diffuse infiltration in the
      right lung field. Laboratory data were remarkable for renal failure accompanied
      by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic
      glomerulonephritis with linear staining of IgG along the glomerular basement
      membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the
      findings of renal biopsy suggested anti-GBM disease, the patient was treated with
      plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of
      his pulmonary symptoms and chest radiograph abnormalities. However, sputum
      culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later.
      Therefore, immunosuppressive agents were discontinued and antituberculous agents
      were administrated. No relapse of pulmonary hemorrhage occurred during the next 1
      year period of follow-up, but the patient did not regain renal function and
      remained on hemodialysis.

PMID- 22950834
TI  - Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast
      cancer cells via Akt pathway modulation.
AB  - Berberine (BBR) is a natural alkaloid with significant antitumor activities
      against many types of cancer cells. In this study, we investigated the molecular
      mechanisms by which BBR repressed the metastatic potential of breast cancer
      cells. BBR was found to downregulate the enzymatic activities and expression
      levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The
      BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the
      Akt/nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) signaling
      pathways. Furthermore, BBR repressed the expression of the Akt protein by
      modulating the mRNA expression level and protein degradation of Akt. In
      conclusion, this study suggests that BBR can reduce the metastatic potential of
      highly metastatic breast cancer cells and may be a useful adjuvant therapeutic
      agent in the treatment of breast cancer by targeting the Akt pathway.

PMID- 22950835
TI  - Olive oil and CVD: accruing evidence of a protective effect.

PMID- 22950836
TI  - New acylated salicin bis-glucosides from Viburnum veitchii.
AB  - The phytochemical study of aerial parts of Viburnum veitchii C.H. Wright, a
      deciduous species originary of Central China, led to the isolation of three
      salicin derivative bis-glucosides, i.e. henryoside (1), and the new structures
      2'b-acetyl-3'b-(3-methylbutyryl)-henryoside (2) and 2'b,6'b-diacetyl-3'b-(3
      methylbutyryl)-henryoside (3). In addition, luteolin, lonicerin, robustaflavone
      and eugenyl-beta-D-glucopyranoside were also isolated. 

PMID- 22950837
TI  - Vacuum-ultraviolet electronic circular dichroism study of methyl alpha-D
      glucopyranoside in aqueous solution by time-dependent density functional theory.
AB  - The vacuum-ultraviolet (VUV) electronic circular dichroism (ECD) spectrum of
      methyl alpha-D-glucopyranoside (methyl alpha-D-Glc) was measured down to 163 nm
      in aqueous solution using a synchrotron-radiation VUV-ECD spectrophotometer. The
      spectrum exhibited two characteristic ECD peaks around 170 nm, which depend on
      the trans (T) and gauche (G) configurations of the hydroxymethyl group at C-5. To
      elucidate the influences of the T and G configurations on the spectrum, the ECD
      spectra of three rotamers (alpha-GT, alpha-GG, and alpha-TG) of methyl alpha-D
      Glc were calculated using time-dependent density functional theory (TDDFT)
      combined with molecular dynamics simulation. A linear combination of the ECD
      spectra of these three rotamers, which differ markedly from each other, produced
      a methyl alpha-D-Glc spectrum similar to that observed experimentally. The
      spectrum was assignable to the n-sigma* transitions of the ring oxygen and
      methoxy oxygen with minor contributions from the hydroxyl oxygen. The differences
      in alpha-GT, alpha-GG, and alpha-TG spectra were attributed to fluctuations of
      the configurations of the hydroxymethyl group at C-5 and the hydroxyl group at C
      4, which strongly affected the orientations of intramolecular hydrogen bonds
      around the ring oxygen. These findings demonstrate that combining VUV-ECD and
      TDDFT is useful for structural characterization of saccharides in aqueous
      solution.

PMID- 22950838
TI  - Processing of syllables during handwriting: effects of graphomotor constraints.
AB  - The processing of syllables during the writing of isolated words has been shown
      to occur either before or during the writing of the word containing them. To
      demonstrate that this difference is related to graphomotor constraints,
      participants copied bi- and trisyllabic words three times, in four conditions
      where graphomotor constraints were gradually increased. As expected, latencies
      were only affected by syllable number in the low-constraint condition. In all
      four conditions, interletter intervals at syllable boundaries were longer than
      intrasyllabic interletter intervals. The difference between inter- and
      intrasyllabic intervals increased with the level of graphomotor constraint. Taken
      together, these findings indicate that under low graphomotor-constraint
      conditions, all the syllable processing takes place prior to the writing of a
      word, whereas under higher graphomotor-constraint conditions, syllable processing
      is more sequential, each syllable being processed just before it is written.

PMID- 22950839
TI  - TNFalpha enhances TLR3-dependent effects on MMP-9 expression in human mesangial
      cells.
AB  - The role of MMPs (matrix metalloproteinases) in kidney diseases has been widely
      accepted, where they can regulate inflammatory response because of their effects
      on both recruitment and survival of inflammatory cells. TNFalpha (tumour necrosis
      factor alpha) has also been implicated in the pathogenesis of inflammatory kidney
      diseases, including forms of glomerulonephritis associated with viral diseases.
      Previously, we established the functional linkage between viral receptors of the
      innate immune system, the TLRs (Toll-like receptors) and control of MMP activity
      in human MC (mesangial cells). Expression levels of MMP-2, MMP-7, MMP-9, TIMP-1
      (tissue inhibitor of metalloproteinase 1) and TIMP-2 in human MC in culture were
      analysed by RT-PCR (reverse transcription-PCR). TNFalpha significantly enhanced
      the TLR3-dependent induction of MMP-9 in human MC. Expression levels of MMP-2,
      TIMP-1 and TIMP-2 were not significantly affected by the activation of TLR3 or
      TNFalpha stimulation. No significant MMP-7 expression was found. We conclude that
      the role of MMP-9 in chemotaxis, activation and proliferation of inflammatory
      cells is amplified by TNFalpha originating from infiltrating cells, especially
      monocytes, producing a regulatory loop that potentially leads to a self
      propagating inflammation.

PMID- 22950840
TI  - Isotyping the human TOMM40 variable-length polymorphism by gene amplification and
      restriction digest.
AB  - Recent studies have shown that the translocase of outer mitochondrial membrane 40
      homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which
      is associated with an increase in AD incidence among APOE 3 carriers. Current
      methods to isotype the poly-T region rely on long PCR, subcloning and sequencing
      to distinguish among the allelic variants. While such methods are extremely
      accurate as well as quantitative in determining the number of T residues in the
      poly-T region, the process can be cumbersome, time consuming and expensive to
      employ in routine laboratories. To this end, we have developed a quick and simple
      method to isotype the human TOMM40 variable length polymorphism using a PCR- and
      restriction digest-based approach, enabling rapid genotyping of TOMM40 variants.

PMID- 22950841
TI  - Health insurance-motivated disability enrollment and the ACA.

PMID- 22950842
TI  - Health care reform and the dynamics of insurance coverage--lessons from
      Massachusetts.

PMID- 22950843
TI  - Amphiphile behavior in mixed solvent media I: self-aggregation and ion
      association of sodium dodecylsulfate in 1,4-dioxane-water and methanol-water
      media.
AB  - Mixed aquo-organic solvents are used in chemical, industrial, and pharmaceutical
      processes along with amphiphilic materials. Their fundamental studies with
      reference to bulk and interfacial phenomena are thus considered to be important,
      but such detailed studies are limited. In this work, the interfacial adsorption
      of sodium dodecylsulfate (SDS, C12H25SO4(-)Na(+)) in dioxane-water (Dn-W) and
      methanol-water (Ml-W) media in extensive mixing ratios along with its bulk
      behavior have been investigated. The solvent-composition-dependent properties
      have been identified, and their quantifications have been attempted. The SDS
      micellization has been assessed in terms of different solvent parameters, and the
      possible formation of an ion pair and triple ion of the colloidal electrolyte,
      C12H25SO4(-)Na(+) in the Dn-W medium has been correlated and quantified. In the
      Ml-W medium at a high volume percent of Ml, the SDS amphiphile formed special
      associated species instead of ion association. The formation of self-assembly and
      the energetics of SDS in the mixed solvent media have been determined and
      assessed using conductometry, calorimetry, tensiometry, viscometry, NMR, and DLS
      methods. The detailed study undertaken herein with respect to the behavior of SDS
      in the mixed aquo-organic solvent media (Dn-W and Ml-W) is a new kind of
      endeavor.

PMID- 22950844
TI  - Reluctant to train, reluctant to prescribe: barriers to general practitioner
      prescribing of opioid substitution therapy.
AB  - Opioid substitution therapy (OST) is a well-recognised, evidence-based treatment
      for opioid dependence. Since the early 1990s, Australia has used a community
      based general practitioner (GP) model ofprescribing, particularly within the
      state of Victoria, where over 85% of OST prescribing is undertaken by GPs in
      community settings. Yet the majority of GPs invited to complete the required OST
      training decline the offer, while of those who complete training, the majority
      prescribe to few or no patients. This study aimed to determine the reasons for
      this. Twenty-two in-depth interviews were conducted with Victorian GPs exploring
      the reasons why the majority declined training, and for trained GPs, why they
      prescribed to few or no patients in the first 12 months after training. General
      practitioners who declined to train were predominantly influenced by negative
      experiences with drug-seeking patients, although other secondary reasons also
      affected their decision. Some GPs who completed the training were prevented from
      prescribing by several structural and operational barriers, many of which could
      be addressed. Fear of deskilling with time became a further impediment. General
      practitioners who became regular prescribers were highly committed with lengthy
      general practice experience. Concerns exist about the recruitment process for OST
      prescriber training, where nearly all GPs decline the offer of training, and the
      barriers that prevent GPs prescribing after training. Action is needed to address
      barriers to GP OST training and prescribing, and further research is necessary to
      ascertain measures required to facilitate long-term prescribing.

PMID- 22950845
TI  - 'This is a forever project': supporting lifestyle changes in a regional
      Queensland community-based cardiac rehabilitation program.
AB  - Cardiac rehabilitation programs throughout the world have struggled for several
      years to attract more participants and facilitate behaviour changes in these
      clients. Over the past few years, there has been an increased level of attention
      in the role that self-efficacy and social support may play in this respect. The
      main aim of this study was to explore self-efficacy and social support within a
      regional, community-based cardiac rehabilitation program that does not adhere to
      traditional cardiac rehabilitation structures. Twelve participants were
      interviewed and two major themes emerged from the thematic analysis of the
      interview transcripts: making personal lifestyle changes; and supportive
      environment for lifestyle changes. Although this study is exploratory in nature,
      it has highlighted the significance of social support from within a program as
      opposed to participants' friends and family, the subject of most social-support
      research. It also contributes to the challenges others are starting to make
      regarding the limited timeframes associated with traditional cardiac
      rehabilitation programs, suggesting more time may be needed to build firmer
      psychosocial foundations for behaviour change after cardiac events. 

PMID- 22950846
TI  - The study design and methodology for the ARCHER study--adolescent rural cohort
      study of hormones, health, education, environments and relationships.
AB  - BACKGROUND: Adolescence is characterized by marked psychosocial, behavioural and
      biological changes and represents a critical life transition through which adult
      health and well-being are established. Substantial research confirms the role of
      psycho-social and environmental influences on this transition, but objective
      research examining the role of puberty hormones, testosterone in males and
      oestradiol in females (as biomarkers of puberty) on adolescent events is lacking.
      Neither has the tempo of puberty, the time from onset to completion of puberty
      within an individual been studied, nor the interaction between age of onset and
      tempo. This study has been designed to provide evidence on the relationship
      between reproductive hormones and the tempo of their rise to adult levels, and
      adolescent behaviour, health and wellbeing. METHODS/DESIGN: The ARCHER study is a
      multidisciplinary, prospective, longitudinal cohort study in 400 adolescents to
      be conducted in two centres in regional Australia in the State of New South
      Wales. The overall aim is to determine how changes over time in puberty hormones
      independently affect the study endpoints which describe universal and risk
      behaviours, mental health and physical status in adolescents. Recruitment will
      commence in school grades 5, 6 and 7 (10-12 years of age). Data collection
      includes participant and parent questionnaires, anthropometry, blood and urine
      collection and geocoding. Data analysis will include testing the reliability and
      validity of the chosen measures of puberty for subsequent statistical modeling to
      assess the impact over time of tempo and onset of puberty (and their interaction)
      and mean-level repeated measures analyses to explore for significant upward and
      downward shifts on target outcomes as a function of main effects. DISCUSSION: The
      strengths of this study include enrollment starting in the earliest stages of
      puberty, the use of frequent urine samples in addition to annual blood samples to
      measure puberty hormones, and the simultaneous use of parental questionnaires.

PMID- 22950847
TI  - Mononuclear five- and six-coordinate iron hydrazido and hydrazine species.
AB  - This article describes the synthesis and characterization of several low-spin
      iron(II) complexes that coordinate hydrazine (N(2)H(4)), hydrazido (N(2)H(3)(-)),
      and ammonia. The sterically encumbered tris(di-meta-terphenylphosphino)borate
      ligand, [PhBP(mter)(3)](-), is introduced to provide access to species that
      cannot be stabilized with the [PhBP(Ph)(3)](-) ligand ([PhBP(R)(3)](-) =
      PhB(CH(2)PR(2))(3)(-)). Treatment of [PhBP(mter)(3)]FeMe with hydrazine generates
      the unusual 5-coordinate hydrazido complex [PhBP(mter)(3)]Fe(eta(2)-N(2)H(3))
      (1), in which the hydrazido serves as an L(2)X-type ligand. Upon coordination of
      an L-type ligand, the hydrazido shifts to an LX-type ligand, generating
      [PhBP(mter)(3)]Fe(L)(eta(2)-N(2)H(3)) (L = N(2)H(4) (2) or NH(3) (3)). In
      contrast, treatment of [PhBP(Ph)(3)]FeMe with hydrazine forms the adduct
      [PhBP(Ph)(3)]Fe(Me)(eta(2)-N(2)H(4)) (5). Complex 5 is thermally unstable to
      methane loss, generating intermediate [PhBP(Ph)(3)]Fe(eta(2)-N(2)H(3)), which
      undergoes bimolecular coupling to produce {[PhBP(Ph)(3)]Fe}(2)(MU-eta(1):eta(1)
      N(2)H(4))(MU-eta(2):eta(2)-N(2)H(2)). The oxidation of these and related
      hydrazine and hydrazido species is also presented. For example, oxidation of 1 or
      5 with Pb(OAc)(4) results in disproportionation of the N(2)H(x) ligand (x = 3,
      4), and formation of [PhBP(R)(3)]Fe(NH(3))(OAc) (R = Ph (9) and mter (11)).

PMID- 22950848
TI  - Protective effect of infliximab on ischemia/reperfusion-induced damage in rat
      kidney.
AB  - OBJECTIVE: To investigate the protective effect of infliximab on ischemia
      reperfusion (I/R) injury of the rat kidney. METHODS: Twenty-eight male Wistar
      albino rats were divided into four groups: sham-operated, I/R, I/R with
      infliximab administered before ischemia [I/R + infliximab (bi)], and I/R with
      infliximab administered before reperfusion [I/R + infliximab (br)]. After a right
      nephrectomy to produce damage, the left renal vessels were occluded for 60 min,
      followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by
      measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO),
      glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin
      eosin (H&E)-stained and periodic acid-Schiff (PAS) sections. RESULTS: The MDA and
      MPO levels in the I/R group were significantly higher than in the other groups (p
      < 0.05), and the SOD and GSH levels in the I/R + infliximab (bi) and I/R +
      infliximab (br) groups were significantly higher than in the I/R group (p <
      0.05). However, histological examination revealed that the I/R + infliximab (bi)
      group and the I/R + infliximab (br) group had significantly fewer tubular changes
      and interstitial inflammatory cell infiltration than the I/R group. CONCLUSION:
      These results show that infliximab may protect against I/R injury in the rat I/R
      model.

PMID- 22950849
TI  - Fundamental vibrational frequencies and spectroscopic constants of HOCS+, HSCO+,
      and isotopologues via quartic force fields.
AB  - Besides the nu(1) O-H stretching mode at 3435 cm(-1) for HOCS(+), the fundamental
      vibrational frequencies for this cation and its HSCO(+) isomer have not been
      determined experimentally. Because these systems are analogues to HOCO(+), a
      detected interstellar molecule, and are believed to play an important role in
      reactions of OCS, which has also been detected in the interstellar medium, these
      cations are of importance to interstellar chemistry and reaction surface studies.
      This work provides the fundamental vibrational frequencies and spectroscopic
      constants computed with vibrational perturbation theory (VPT) at second order and
      the vibrational configuration interaction (VCI) method conjoined with the most
      accurate quartic force field (QFF) applied to date for these systems. Our
      computations match experiment to better than 2 cm(-1) for the known O-H stretch.
      Additionally, there is strong agreement in the prediction of the fundamentals
      across methods and choices of QFFs. The consistency in the computations and the
      correspondence for the known mode should give accurate reference data for the
      rovibrational spectra of these cations and their singly substituted isotopologues
      for D, (18)O, and (34)S.

PMID- 22950850
TI  - Contextual influences on children's use of vocal affect cues during referential
      interpretation.
AB  - In three experiments, we investigated 5-year-olds' sensitivity to speaker vocal
      affect during referential interpretation in cases where the indeterminacy is or
      is not resolved by speech information. In Experiment 1, analyses of eye gaze
      patterns and pointing behaviours indicated that 5-year-olds used vocal affect
      cues at the point where an ambiguous description was encountered. In Experiments
      2 and 3, we used unambiguous situations to investigate how the referential
      context influences the ability to use affect cues earlier in the utterance. Here,
      we found a differential use of speaker vocal affect whereby 5-year-olds'
      referential hypotheses were influenced by negative vocal affect cues in advance
      of the noun, but not by positive affect cues. Together, our findings reveal how 5
      year-olds use a speaker's vocal affect to identify potential referents in
      different contextual situations and also suggest that children may be more
      attuned to negative vocal affect than positive vocal affect, particularly early
      in an utterance.

PMID- 22950851
TI  - Evaluation of electrophilic heteroaromatic substitution: synthesis of
      heteroaromatic-fused pyrimidine derivatives via sequential three-component
      heterocyclization.
AB  - A new sequential three-component heterocyclization was developed by reacting
      aromatic and heterocyclic substrates, including aminobenzenes, 1
      aminonaphthalene, 2-aminopyrazines, 5-aminopyrazoles, 3-aminopyridine, 5
      aminopyrimidine, 5-aminoquinoline, and 8-aminoquinoline, with formamide in the
      presence of PBr(3). The reaction gave the corresponding pyrazolo[3,4
      d]pyrimidines in good yields (59-96%), except for aminobenzenes and 3
      aminopyridine. A plausible reaction mechanism involving amidination,
      electrophilic substitution imination, and oxidative cyclization in three steps
      was proposed to account for the heterocyclization. The reactivity of the reaction
      was found proportional to the electrophilicity of the aromatic or heterocyclic
      substrate.

PMID- 22950852
TI  - Introducing the D4 Diagnostic Quadrant as a targeting tool: developing a
      framework for the effectiveness of HIV/AIDS interventions in Tanzania and beyond.
AB  - The current study develops and evaluates a tool to distinguish four different
      categories of educators for the effective delivery of HIV/AIDS health education
      using data from 548 randomly selected participants aged 16 years. The D4
      Diagnostic Quadrant is based on HIV knowledge and sexual practice behaviours and
      indicates four distinct typologies of educator. The discerning educator has high
      HIV/AIDS knowledge and healthy sexual practices. The dissolute educator has high
      HIV/AIDS knowledge but employs unhealthy or risky sexual practices. The decorous
      educator has low HIV/AIDS knowledge but practices healthy sexual practices. The
      disempowered educator has low HIV/AIDS knowledge and employs unhealthy or risky
      sexual practices. The study found that the two categories that will result in the
      most effective behaviour-change interventions are those that target 'discerning'
      and 'decorous' individuals as the educators. Both these categories have
      underlying healthy practices that minimise the risk of HIV transmission. The D4
      Diagnostic Quadrant tool provides information as to existing knowledge and
      beliefs about HIV/AIDS that can inform decisions relating to the allocation of
      scarce resources. The tool will be very useful in the selection process of would
      be educators particularly in health-promotion interventions.

PMID- 22950854
TI  - Microbial metabolism. Part 14. Isolation and bioactivity evaluation of microbial
      metabolites of resveratrol.
AB  - The fungi, Beauveria bassiana (ATCC 13144) and Penicillium chrysogenium (ATCC
      9480) transformed resveratrol to resveratrol-3-O-sulphate. The former, in
      addition, gave 5-methoxyresveratrol-3-O-beta-glucoside with the latter yielding 5
      methoxyresveratrol-3-O-sulphate. The structures were established by spectroscopic
      methods. Evaluation of biological activity of metabolites through a series of
      mammalian cell based assays indicated that resveratrol tends to lose its anti
      inflammatory, cytotoxic and anti-oxidant activities with the substitution of its
      hydroxyl groups.

PMID- 22950853
TI  - Dietary patterns obtained through principal components analysis: the effect of
      input variable quantification.
AB  - Principal components analysis (PCA) is a popular method for deriving dietary
      patterns. A number of decisions must be made throughout the analytic process,
      including how to quantify the input variables of the PCA. The present study aims
      to compare the effect of using different input variables on the patterns
      extracted using PCA on 3-d diet diary data collected from 7473 children, aged 10
      years, in the Avon Longitudinal Study of Parents and Children. Four options were
      examined: weight consumed of each food group (g/d), energy-adjusted weight,
      percentage contribution to energy of each food group and binary intake
      (consumed/not consumed). Four separate PCA were performed, one for each intake
      measurement. Three or four dietary patterns were obtained from each analysis,
      with at least one component that described 'more healthy' and 'less healthy'
      diets and one component that described a diet with high consumption of meat,
      potatoes and vegetables. There were no obvious differences between the patterns
      derived using percentage energy as a measurement and adjusting weight for total
      energy intake, compared to those derived using gram weights. Using binary input
      variables yielded a component that loaded positively on reduced fat and reduced
      sugar foods. The present results suggest that food intakes quantified by gram
      weights or as binary variables both resulted in meaningful dietary patterns and
      each method has distinct advantages: weight takes into account the amount of each
      food consumed and binary intake appears to describe general food preferences,
      which are potentially easier to modify and useful in public health settings.

PMID- 22950855
TI  - Impacts and outcomes of diabetes care in a high risk remote Indigenous community
      over time: implications for practice.
AB  - The aim of this study was to determine diabetes care processes and intermediate
      clinical outcomes in a remote primary care service in 2009 compared with 2004. A
      retrospective review of diabetes care from January 2009 to January 2010 was
      conducted using a chronic disease register (Project Ferret). Completeness of
      ascertainment was verified by a manual audit of charts. The results from this
      audit were compared with a similar study conducted in this community in 2004. The
      main outcome measure was diabetic management: in terms of (a) regular monitoring
      of diabetic care processes, and (b) compliance with national optimal management
      guidelines and comparison with diabetic outcomes data from a 2004 audit and the
      National data from 2009. People with diabetes on the register increased from 60
      in 2004 to 77 in 2009. They were younger and heavier with a shorter duration of
      diagnosed diabetes. Recording of diabetic care processes in 2009 decreased
      between 5 and 32% compared with 2004 data. Intermediate clinical measures (e.g.
      glycosylated haemoglobin, blood pressure, triglycerides, albumin creatinine
      ratio) indicate stable or poorer diabetic control across all measures except
      total cholesterol. When compared with non-Indigenous diabetics, diabetes is
      diagnosed earlier and rates of smoking, hypertension, dyslipidaemia and diabetic
      nephropathy are higher in this population. Insulin use appears to be lower in the
      study population than reported in the national sample. Improved diabetic care
      processes and outcomes reported from 1999 to 2003 have not been sustained, and
      intermediate clinical measures have become more adverse over a 5 year period in
      this high risk remote community. Chronic care systems, including quality
      improvement, require renewed investment. 

PMID- 22950856
TI  - Effect of hydrophobic interactions on volume and thermal expansivity as derived
      from micelle formation.
AB  - Volumetric parameters have long been used to elucidate the phenomena governing
      the stability of protein structures, ligand binding, or transitions in
      macromolecular or colloidal systems. In spite of much success, many problems
      remain controversial. For example, hydrophobic groups have been discussed to
      condense adjacent water to a volume lower than that of bulk water, causing a
      negative contribution to the volume change of unfolding. However, expansivity
      data were interpreted in terms of a structure-making effect that expands the
      water interacting with the solute. We have studied volume and expansivity effects
      of transfer of alkyl chains into micelles by pressure perturbation calorimetry
      and isothermal titration calorimetry. For a series of alkyl maltosides and
      glucosides, the methylene group contribution to expansivity was obtained as 5
      uL/(mol K) in a micelle (mimicking bulk hydrocarbon) but 27 uL/(mol K) in water
      (20  degrees C). The latter value is virtually independent of temperature and
      similar to that obtained from hydrophobic amino acids. Methylene contributions of
      micellization are about -60 J/(mol K) to heat capacity and 2.7 mL/mol to volume.
      Our data oppose the widely accepted assumption that water-exposed hydrophobic
      groups yield a negative contribution to expansivity at low temperature that would
      imply a structure-making, water-expanding effect.

PMID- 22950857
TI  - Exogenous long-term treatment with 17beta-oestradiol alters the innervation
      pattern in pig ovary.
AB  - The aim of the present study was to determine the effect of long-term 17beta
      oestradiol (E2) exposure, a simulation of pathological states that occur with
      oestrogen overproduction, on the innervation patterns of ovaries in adult gilts.
      The intraovarian distribution and density of nerve fibres immunoreactive (IR) to
      protein gene product (PGP) 9.5 and containing dopamine-beta-hydroxylase (DBH),
      neuropeptide Y (NPY), somatostatin (SOM) and galanin (GAL) were determined. From
      Day 4 of the first oestrous cycle to Day 20 of the second cycle studied,
      experimental gilts were injected with E2 (1000MUg every 12h) whereas control
      gilts were injected with corn oil. After E2 administration, there was an increase
      in the number of PGP9.5-, DBH-, NPY- and GAL-IR fibres. Numerous PGP9.5-IR
      terminals were observed within the ground plexus around secondary follicles and
      small or medium tertiary follicles. Long-term E2 treatment increased the density
      of DBH- and NPY-IR fibres in the cortical part of the ground plexus, DBH- and GAL
      IR fibres in the medullary part of the ground plexus, DBH-IR fibres near small
      and medium tertiary follicles and NPY-IR fibres around medullary arteries. The
      data indicate that long-term exposure of gilts to E2 increases the total number
      of intraovarian fibres, including sympathetic fibres. These results suggest that
      elevated E2 levels that occur during pathological states may affect the
      innervation patterns of ovaries and their function(s).

PMID- 22950858
TI  - Identifying intimate partner violence when screening for health and lifestyle
      issues among women attending general practice.
AB  - Intimate partner violence is a common but under-recognised issue for women
      attending primary care. There is a lack of studies looking at women's comfort to
      discuss and openness to getting help for health issues, including fear of a
      partner, in primary care. Female patients (aged 16-50 years) attending 55 general
      practitioners (GPs) in Victoria, Australia were mailed a brief survey that
      screened for health and lifestyle issues, comfort to discuss these issues and
      intention to get help in primary care. Needing physical activity and smoking were
      the issues women were most comfortable to discuss; followed by difficulty
      controlling what and/or how much is eaten, feeling down, depressed, hopeless or
      worried, and use of drugs or alcohol. Women were least comfortable to discuss
      fear of a partner and least likely to seek help for it from the GP or primary
      care nurse. However, as with the other issues, acceptability of being asked in a
      survey was high. All health and lifestyle issues predicted fear of a partner.
      Primary care practitioners should be aware of this complex major public health
      issue especially when carrying out preventive health care.

PMID- 22950859
TI  - Product identification and safety evaluation of aflatoxin B1 decontaminated by
      electrolyzed oxidizing water.
AB  - In this study with aflatoxin-contaminated peanuts, the effectiveness of
      electrolyzed oxidizing water (EOW) in the decontamination of aflatoxin B(1) was
      investigated. The aflatoxin B(1) content was markedly reduced upon treatment with
      EOW, particularly with neutral electrolyzed oxidizing water (NEW). The conversion
      product of EOW treatment was isolated and identified as 8-chloro-9-hydroxy
      aflatoxin B(1) (compound 1), which is an amphiphilic molecule, in contrast to fat
      soluble aflatoxin B(1). A mutagenic response study revealed that the number of
      revertants per plate after treatment of bacterial strains TA-97, TA-98, TA-100,
      and TA-102 with NEW was within the standard value range. The HepG2 cell viability
      assay yielded an IC(50) value of compound 1 approximately 150 mM. This study
      indicates that EOW had the ability to decontaminate aflatoxin B(1), and the
      conversion product, compound 1, did not exhibit mutagenic activity or cytotoxic
      effects.

PMID- 22950860
TI  - Isatins as privileged molecules in design and synthesis of spiro-fused cyclic
      frameworks.

PMID- 22950862
TI  - DNA methyltransferase inhibitors in acute myeloid leukemia: discovery, design and
      first therapeutic experiences.
AB  - INTRODUCTION: DNA methylation is an epigenetic change mediated by DNA
      methyltranferases (DNMTs), which are promising epigenetic targets for the
      treatment of acute myeloid leukemia (AML). This is evidenced by the two DNMT
      inhibitors (azacitidine and decitabine) approved by the Food and Drug
      Administration of the United States for the treatment of high-risk
      myelodysplastic syndromes and the first clinical data available in AML. AREAS
      COVERED: This paper reviews data from the international literature regarding the
      design, sites of impact and pharmacodynamic characteristics of DNMT inhibitors,
      and their first clinical experiences in AML. EXPERT OPINION: The strongest
      advances in epigenetic therapy have been in the treatment of AML. There are now
      an increasing number of DNMT inhibitors. These agents may be potentially
      administered at different times of leukemia therapy: before or instead of
      chemotherapy, as maintenance therapy, prior to allogeneic stem cell transplant
      (SCT) or after relapse following SCT.

PMID- 22950861
TI  - Safety and efficacy of topiramate in neonates with hypoxic ischemic
      encephalopathy treated with hypothermia (NeoNATI).
AB  - BACKGROUND: Despite progresses in neonatal care, the mortality and the incidence
      of neuro-motor disability after perinatal asphyxia have failed to show
      substantial improvements. In countries with a high level of perinatal care, the
      incidence of asphyxia responsible for moderate or severe encephalopathy is still
      2-3 per 1000 term newborns. Recent trials have demonstrated that moderate
      hypothermia, started within 6 hours after birth and protracted for 72 hours, can
      significantly improve survival and reduce neurologic impairment in neonates with
      hypoxic-ischemic encephalopathy. It is not currently known whether
      neuroprotective drugs can further improve the beneficial effects of hypothermia.
      Topiramate has been proven to reduce brain injury in animal models of neonatal
      hypoxic ischemic encephalopathy. However, the association of mild hypothermia and
      topiramate treatment has never been studied in human newborns. The objective of
      this research project is to evaluate, through a multicenter randomized controlled
      trial, whether the efficacy of moderate hypothermia can be increased by
      concomitant topiramate treatment. METHODS/DESIGN: Term newborns (gestational age
      >= 36 weeks and birth weight >= 1800 g) with precocious metabolic, clinical and
      electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be
      randomized, according to their EEG pattern, to receive topiramate added to
      standard treatment with moderate hypothermia or standard treatment alone.
      Topiramate will be administered at 10 mg/kg once a day for the first 3 days of
      life. Topiramate concentrations will be measured on serial dried blood spots. 64
      participants will be recruited in the study. To evaluate the safety of topiramate
      administration, cardiac and respiratory parameters will be continuously
      monitored. Blood samplings will be performed to check renal, liver and metabolic
      balance. To evaluate the efficacy of topiramate, the neurologic outcome of
      enrolled newborns will be evaluated by serial neurologic and neuroradiologic
      examinations. Visual function will be evaluated by means of behavioural
      standardized tests. DISCUSSION: This pilot study will explore the possible
      therapeutic role of topiramate in combination with moderate hypothermia. Any
      favourable results of this research might open new perspectives about the
      reduction of cerebral damage in asphyxiated newborns.

PMID- 22950863
TI  - Evidence that enzyme processivity mediates differential Abeta production by PS1
      and PS2.
AB  - The gamma-secretase complex cleaves the carboxy-terminal 99 residue (C99)
      fragment of the amyloid precursor protein (APP) to generate the amyloid-beta
      (Abeta) peptide. The catalytic activity of this complex is mediated either by the
      presenilin- 1 (PS1) or the presenilin-2 (PS2) subunit. In vitro and in vivo
      studies have demonstrated that PS1-containing complexes generate more total Abeta
      product than PS2-containing complexes, indicating greater cleavage activity by
      PS1- containing gamma-secretase complexes at the APP gamma-site. However, it
      remains untested whether gamma-secretase cleavage at the APP -site, which
      precedes gamma-site cleavage and produces the physiologically active APP
      intracellular domain (AICD), follows the same rule. Using a novel Swedish APP-GVP
      substrate to facilitate the parallel detection of Abeta and AICD products from
      PS1-/-/PS2-/- cells co-transfected with either PS1 or PS2, we observed that while
      PS1 generates more total Abeta product than PS2, consistent with published
      reports, PS1 and PS2 unexpectedly generate equal amounts of AICD product. We also
      observed that PS1 and PS2 produce equivalent amounts of Notch intracellular
      domain (NICD), indicating equal cleavage activity at the Notch S3-site (the
      corollary of the APP -site). Our findings suggest that processivity differences
      between PS1 and PS2 underlie the differential production of Abeta peptide. Taken
      together these findings offer novel insights into gamma- secretase biology and
      have important implications for therapeutically targeting gamma-secretase.

PMID- 22950864
TI  - Apolipoprotein E4 serum concentration for increased sensitivity and specificity
      of diagnosis of drug treated Alzheimer's disease patients vs. drug treated
      parkinson's disease patients vs. age-matched normal controls.
AB  - BACKGROUND: Inasmuch as Alzheimer's disease (AD) is difficult to diagnose,
      patients with suspected dementias are often given FDA approved medications,
      including donepezil, rivastigmine, memantine HCl, or a combination, prior to
      diagnosis, and some respond with improved cognition. The present study
      demonstrates how concentrations of a select group of serum protein biomarkers can
      provide the basis for sensitive and specific differential diagnosis of AD in drug
      treated patients. Optimization is addressed by taking into account whether the
      patients and controls have or do not have increased risk of AD die to the
      presence or absence of Apolipoprotein E4. METHODS: For differential diagnosis of
      AD, prospectively collected newly drawn blood serum samples were obtained from
      drug treated Alzheimer's disease and Parkinson's disease patients from a first
      (39 drug treated DTAD, and 31 age matched normal controls) and second medical
      center (56 drug treated DTPD, 47 age-matched normal controls). Analytically
      validated quantitative 2D gel electrophoresis (%CV <= 20%; LOD >= 0.5 ng/spot,
      300 MUg/ml of blood serum) was employed with patient and control sera for
      differential diagnosis of AD. Protein quantitation was subjected to statistical
      analysis by single variable Dot, Box and Whiskers and Receiver Operator
      Characteristics (ROC) plots for individual biomarker performance, and
      multivariate linear discriminant analysis for joint performance of groups of
      biomarkers. Protein spots were identified and characterized by LC MS/MS of in-gel
      trypsin digests, amino acid sequence spans of the identified peptides, and the
      protein spot molecular weights and isoelectric points. RESULTS: The single
      variable statistical profiles of 58 individual protein biomarker concentrations
      of the DTAD patient group differed from those of the normal and/or the disease
      control groups. Multivariate linear discriminant analysis of blood serum
      concentrations of the 58 proteins distinguished drug treated Alzheimer's disease
      (DTAD) patients from drug treated Parkinson's disease (DTPD) patients and age
      matched normal controls (collectively not-DTAD, DTAD Sensitivity 87.2%, Not-DTAD
      Specificity 87.2). Moreover, when the patients and controls were stratified into
      carriers or non-carriers of Alzheimer's high risk Apolipoprotein E 4 allele
      and/or the Apolipoprotein E4 protein, the DTAD, DTPD and control Apo E4 (+)
      profiles were more divergent from one another than the corresponding Apo E4 (-)
      profiles. Multivariate stepwise linear discriminant analysis selected 17 of the
      58 biomarkers as optimal and complimentary for distinguishing Apo E4 (+) DTAD
      patients from Apo E4 (+) DTPD and Apo E4 (+) controls (collectively Apo E4 (+)
      not-DTAD, DTAD Sensitivity 100%, not-DTAD Specificity 100%) and 22 of the 58
      biomarkers for distinguishing Apo E4 (-) DTAD patients from Apo E4 (-) DTPD and
      Apo E4 (-) controls (collectively Apo E4 (-) not-DTAD, DTAD Sensitivity 94.4%,
      not- DTAD Specificity 94.4%). Only 6 of the selected proteins were common to both
      the Apo E4 (+) and the Apo E4 (-) discriminant functions. Recombining of the
      results of Apo E4 (+) and Apo E4 (-) discriminations provided overall sensitivity
      for total DTAD of 97.4% and specificity for total not-DTAD of 95.7%. CONCLUSIONS:
      These results can form the basis of a blood test for differential diagnosis of
      Alzheimer's disease patients already under treatment (DTAD) by anti dementia
      drugs, including donepezil, rivastigmine, memantine HCl, or a combination
      thereof. Also, the profile differences and the rise in specificity and
      sensitivity obtained by handling the Apo E4 (+) and Apo E4 (-) groups separately
      supports the concept that they are different patient and control populations in
      terms of the "normal" physiology, the pathophysiology of disease, and the
      response to drug treatment. Taking that into account enables increased
      sensitivity and specificity of differential diagnosis of Alzheimer's disease.

PMID- 22950865
TI  - All cognitive systems but speed and visuospatial functions reduce the effect of
      CSF pathology on other systems.
AB  - The concept of reserve can be conceived as differences in the ability to
      compensate for pathology by recruiting additional or alternative networks. The
      purpose of this study was to examine whether certain cognitive systems may
      compensate for the effect of CSF amyloid beta 42 (Abeta42) and total tau (T-tau)
      on other cognitive systems. Five hundred and nine participants underwent
      neuropsychological examination and lumbar puncture. Multiple regression was
      performed with interaction terms to test whether a cognitive system reduced the
      impact of CSF pathology on other systems. All cognitive systems except speed and
      visuospatial functions were associated with reduced effects of T-tau and Abeta42
      on semantic memory, working memory and visuospatial abilities. The burden of
      Abeta42 was reduced more often than that of T-tau. Our results suggest that most
      cognitive systems may be beneficial to maintenance of cognitive performance
      despite CSF burden. The results support the notion of cognitive reserve.

PMID- 22950866
TI  - New assay for old markers-plasma beta amyloid of mild cognitive impairment and
      Alzheimer's disease.
AB  - Although there is a consensus on the reduced levels of Abeta1-42 in the CSF of
      patients with AD, studies of plasma Abeta levels were inconsistent and have
      limited clinical value. We developed an immunomagnetic reduction assay (IMR) to
      determine the plasma levels of Abeta. We surveyed patients with varying AD
      severity (CDR = 0.5, n=16; CDR >= 1, n=18) and controls (n=26). Significant group
      differences were apparent in the levels of Abeta1-42 (F = 5.54, p = 0.002) and
      the Abeta1-42/Abeta1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed
      significant differences in the Abeta1-42 levels of controls and AD patients (p =
      0.001) and in the Abeta1-42/Abeta1-40 ratio of control, MCI and AD subjects (all
      p <= 0.001). Regression analysis of Abeta1-42/Abeta1-40 ratios on dementia
      severity showed an adjusted R2 of 0.553 (p = 0.001). We identified a cut-off of
      16.1 pg/ml for Abeta1-42 to differentiate control subjects from patients (both AD
      and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off
      value of 0.303 for Abeta1-42/Abeta1-40 ratios with 85.3% sensitivity and 96.2%
      specificity. APOE 4 carriers had significantly higher Abeta1-42/Abeta1-40 ratios
      than the non-carriers (F = 4.839, p = 0.015). An independent group of case
      control subjects validated both cut-off values for Abeta1-42/Abeta1-40 (100%
      sensitivity and 83.3% specificity) and for Abeta1-42 (100% sensitivity and 75.3%
      specificity). In a subgroup of longitudinal follow- up study, we found that the
      plasma Abeta was relatively stable with an interval of approximately 3 months. In
      conclusion, we found that the plasma Abeta1-42 is a useful biomarker for AD. The
      Abeta1-42/Abeta1-40 ratio improves the diagnostic power of the plasma Abeta
      biomarkers. The iron nanoparticles and IMR provides a novel method to measure
      plasma Abeta and could serve as an important clinical tool for the diagnosis of
      neurodegenerative diseases.

PMID- 22950867
TI  - Look again, and not just at behavioural and cognitive psychotherapy.

PMID- 22950868
TI  - The rescripting of pain images.
AB  - BACKGROUND: The majority of pain sufferers experience images when in pain. The
      most distressing of these images (the Index image) provokes intense emotional
      reactions, appraisal shifts, and increases in pain. The ability of pain sufferers
      to rescript their Index images, and the consequences of doing so, remain to be
      determined. AIMS: To assess the effects upon emotions, appraisals and pain
      experience of rescripting Index images in pain sufferers. METHOD: The Index
      images of a group of 55 pain sufferers were assessed using a voluntary image
      induction procedure (VIE) to obtain basal levels of pain, appraisal and emotion.
      Participants were than randomly allocated to one of two groups: Rescripted Image
      repetition or Index Image repetition. The two groups were compared on their
      responses to their Index and Rescripted images respectively. RESULTS: The
      participants found it easy to rescript their distressing Index images. During
      rescripting, they reported dramatic reductions in emotion, negative appraisals,
      and pain. The clinically and statistically significant decrements in pain were
      found independent of reductions in emotion. The pain levels during rescripting
      were significantly below their basal levels, with 49% reporting no pain at all
      while viewing a rescripted image. These changes were not a function of image
      repetition. CONCLUSION: Index images of pain sufferers can be easily elicited and
      rescripted. Rescripting leads to remarkable reductions in emotion, cognitions and
      pain levels that are not attributable to image repetition. The significant
      reductions in pain were independent of reductions in emotion. The implications of
      these results for CBT approaches to pain management are considered.

PMID- 22950869
TI  - Structural modulation and phase transitions in La2CoO(4.14) investigated by
      synchrotron X-ray and neutron single-crystal diffraction.
AB  - We report a combined synchrotron X-ray and neutron diffraction study on as-grown
      La(2)CoO(4.14) single-crystal from 10 to 470 K. Unprecedented structural features
      in terms of a (3 + 2)D incommensurate modulation have been detected and
      characterized in the Low Temperature Orthorhombic (LTO) phase already at room
      temperature despite the complex twinning that was unravelled. A new intermediate
      phase between the LTO and High Temperature Tetragonal (HTT) phases has been
      observed for the first time (in the range of 413-433 K). The transformation from
      LTO to this so-called HTLO (High Temperature Less Orthorhombic) phase is
      associated to a lowering of orthorhombicity and a loss of one modulation vector,
      yielding a (3 + 1)D incommensurate modulation. Conversely, above 433 K the HTT
      phase appears as nonmodulated but exhibits a strong dynamic disorder of CoO(6)
      octahedra, which has been characterized in detail by reconstruction of nuclear
      densities via the Maximum Entropy Method (MEM).

PMID- 22950870
TI  - Development of time sensitivity: duration ratios in time bisection.
AB  - This study investigated the development of children's abilities to discriminate
      durations as a function of their ratio and examined whether the ability to
      discriminate durations that differed by a very difficult ratio is related to the
      development of attention capacities. Children aged 5 and 8 years, as well as
      adults, performed a series of temporal bisection tasks with a ratio between the
      short and the long anchor duration that was changed to control the difficulty of
      the task (5:6, 2:3, and 1:2) in two duration ranges (<1 s and >3 s). In addition,
      they completed neuropsychological tests in order to assess their short-term
      memory, working memory, and visual attention abilities. The results showed that,
      at ratios of 2:3 and 1:2, most participants were able to discriminate the anchor
      durations in bisection. However, their sensitivity to time improved, whatever the
      duration range, both as the distance between the anchor durations increased and
      with increasing age. For the smallest duration ratio (5:6), few of the children
      were able to discriminate the anchor durations in the bisection task in
      comparison to adults. Hierarchical regression analyses performed on the
      neuropsychological tests revealed that, for the 2:3 ratio between anchor
      durations, the participants' visual attention scores explained a large part of
      the variance in time sensitivity. The children's lower temporal sensitivity was
      probably due to their limited visual attention abilities, thus explaining the
      difficulty they experienced in discriminating very close durations (5:6).

PMID- 22950871
TI  - Glycopolymer brushes for the affinity adsorption of RCA120: effects of thickness,
      grafting density, and epitope density.
AB  - The interactions between glycopolymer brushes and lectin are very important for
      the development of affinity membrane chromatography in protein separation. Here,
      we report the combination of surface-initiated atom transfer radical
      polymerization (SI-ATRP) and surface plasmon resonance (SPR) to investigate the
      relationship between the structure of glycopolymer brushes and the affinity
      adsorption of lectin. The glycopolymer brushes were fabricated from self-assembly
      of 11-mercapto-1-undecanol (MUD)/1-undecanethiol (UDT) mixture, immobilization of
      ATRP initiators, and then SI-ATRP of 2-lactobionamidoethyl methacrylate (LAMA).
      Brush thickness and grafting density were adjusted by controlling polymerization
      time and thiol ratio in MUD/UDT mixture, respectively. Sugar epitope density was
      also controlled through copolymerization of 2-hydroxylethyl methacrylate (HEMA)
      with LAMA. Ricinus communis agglutinin (RCA(120)), one kind of lectin that can
      bind galactose specifically, was chosen to study the effects of brush
      architectures on lectin adsorption. SPR results indicate not only the thickness
      but also the grafting density and the epitope density of glycopolymer brushes can
      achieve the best performance of sugar cluster effect in affinity adsorption of
      lectin. In addition, the mass transport effect is crucial in the adsorption
      process. We propose that it is important to keep the balance between the sugar
      cluster effect and the mass transport effect in the preparation of high
      performance affinity membrane chromatography.

PMID- 22950872
TI  - Cyclobutene ring-opening of bicyclo[4.2.0]octa-1,6-dienes: access to CF3
      substituted 5,6,7,8-tetrahydro-1,7-naphthyridines.
AB  - An efficient method for the synthesis of novel CF(3)-substituted tetrahydro-1,7
      naphthyridines including cyclic alpha-amino acid derivatives has been developed.
      The method is based on unusual cyclobutene ring-opening of bicyclo[4.2.0]octa-1,6
      dienes with pyrrolidine to afford the corresponding 1,5-diketones followed by
      their heterocyclization. A convenient one-pot procedure has been also elaborated
      starting from readily available trifluoromethylated 1,6-allenynes.

PMID- 22950873
TI  - Electrically tunable damping of plasmonic resonances with graphene.
AB  - Dynamic switching of a plasmonic resonance may find numerous applications in
      subwavelength optoelectronics, spectroscopy, and sensing. Graphene shows a highly
      tunable carrier concentration under electrostatic gating, and this could provide
      an effective route to achieving electrical control of the plasmonic resonance. In
      this Letter, we demonstrate electrical control of a plasmonic resonance at
      infrared frequencies using large-area graphene. Plasmonic structures fabricated
      on graphene enhance the interaction of the incident optical field with the
      graphene sheet, and the impact of graphene is much stronger at mid-infrared
      wavelengths. Full-wave simulations, where graphene is modeled as a 1 nm thick
      effective medium, show excellent agreement with experimental results.

PMID- 22950874
TI  - Filters and hubs: shortening the distance to palliative care evidence.
AB  - Palliative care is an integral part of the care provided by GPs and other primary
      health care providers, and as Australia's population ages and the palliative care
      needs of patients with end stage organ failure are recognised, this area of care
      is likely to increase. Using a knowledge translation framework, two strategies
      have been used to develop resources to support those providing palliative care in
      the community. PubMed searches on a range of common palliative care topics and
      incorporating a palliative care filter provide an easy and validated mechanism to
      retrieve relevant literature. A 'GP Hub' offers knowledge, skills and practical
      advice for GPs who provide palliative care in the community. Both resources are
      freely available within the CareSearch website, ensuring immediate access to
      palliative care information and evidence when it is needed.

PMID- 22950875
TI  - Programming a highly structured ribozyme into complex allostery using RNA
      oligonucleotides.
AB  - RNA possesses great potential for expanding the toolbox currently available to
      synthetic biologists. Here, the modulation of the Hepatitis Delta Virus
      ribozyme's activity with a series of rationally designed aptamers and effector
      RNA oligonucleotides is described. The ribozyme was initially fused with an 18
      nucleotide hairpin structure that abolished its self-cleaving activity. The
      binding of a 14-mer oligonucleotide to the hairpin rescued the self-cleavage in a
      concentration-dependent manner. This modified ribozyme was inserted into the 5'
      UTR of a reporter gene, and the resulting construct was used to demonstrate that
      it is possible to modulate the ribozyme activity in cellulo with the
      oligonucleotide. Subsequently, ribozymes possessing specialized aptamers
      respecting other logic gates were also successfully designed and found to be
      functional in vitro. To our knowledge, this is the first example of HDV ribozyme
      regulation by oligonucleotides, as well as the first allosteric regulation of HDV
      ribozyme in mammalian cells.

PMID- 22950876
TI  - A systematic review of diffusion tensor imaging findings in sports-related
      concussion.
AB  - Sports-related concussion (SRC) is typically associated with functional, as
      opposed to structural, injury. The results of traditional structural neuroimaging
      techniques used to assess SRC tend to be normal in many athletes, and are only
      clinically helpful in ruling out a more serious injury. Diffusion tensor imaging
      (DTI) has increasingly been touted as a method offering greater clinical
      potential in mild traumatic brain injury (mTBI). Despite this, the utility of DTI
      as a clinical tool for diagnosing and managing SRC has received considerably less
      attention than it has in the general TBI research literature. The aim of this
      article is to conduct a systematic review of DTI in SRC, and to provide a focus
      and overview of research findings using this MRI technique in SRC. A systematic
      review of articles published in the English language, up to February 2012, was
      retrieved via PsycINFO((r)), MEDLINE((r)), EMBASE, SPORTDiscus(TM), Scopus, Web
      of Science, and Informit; using the key search terms: diffusion tensor imaging,
      diffusion magnetic resonance imaging, diffusion weighted MRI, diffusion MRI,
      fractional anisotropy, tractography, apparent diffusion coefficient, magnetic
      resonance imaging, mild traumatic brain injury, mTBI, traumatic brain injury,
      concussion, sport, athletic and athlete. Observational, cohort, correlation,
      cross-sectional and longitudinal studies were all included in the current review.
      Results of the review found eight articles that met inclusion criteria, which
      included data on 214 athletes and 96 controls. Seven of eight studies reported
      some type of DTI abnormality, although the neuroanatomical sites involved varied.
      Although considerable methodological variations exist across studies, the current
      review suggests that DTI may possess adequate diagnostic sensitivity to detect
      SRC in affected athletes. Further longitudinal studies are required to
      demonstrate its discriminate validity and prognostic capacity within this field.

PMID- 22950877
TI  - Attitudes of primary health care physician managers toward research: a pre
      experimental study.
AB  - Research in primary health care (PHC) is underdeveloped and scarce, especially in
      developing countries. It is important to understand the attitudes and aspirations
      of PHC physicians for the promotion of research. The aim of this study was to
      determine the attitudes of PHC physician managers toward research in Qassim
      province and to identify barriers that impede performing research in the PHC
      system. The study was based on social cognitive theory framework, and was pre
      experimental with a 'one-group pre-test-post-test' design. The study participants
      were physician managers in PHC administration, Qassim. The participants'
      attitudes were measured by adapting statements from the Attitude Towards Research
      scale. The intervention was the 1-day training program 'Introduction to Research
      in Primary Health Care'. A total of 23 PHC physicians participated in the study.
      The mean age of the participants was 45.4 (+/-1.6) years, and the mean years of
      work experience was 16.2 (+/-2.2) years. Only one participant had an article
      published in a peer-reviewed journal. The results of the study showed that PHC
      physicians had a baseline positive attitude toward research that was further
      enhanced after participating in an introductory research-training program. During
      the pre-test, out of the total score of 63, the mean score on attitude toward
      research was 48.35 (+/-6.8) while the mean total attitude score in the post-test
      was 49.7 (+/-6.6). However, the difference was not statistically significant at
      P<0.05. The item with the highest score regarded the role of research in the
      improvement of health care services, while the lowest-scoring item was about
      support from administration to conduct research. The participants recognised lack
      of skills, lack of training and inadequate resources as major barriers in
      conducting research. Our study results suggest that the PHC physicians' positive
      attitudes toward research can be further improved through in-service training. To
      promote research in PHC in Qassim, regular research-training programs and
      incentives for conducting research should be provided to the PHC physicians. 

PMID- 22950878
TI  - Lipid nanoparticles for cancer therapy: state of the art and future prospects.
AB  - INTRODUCTION: Cancer is a leading cause of death worldwide and it is estimated
      that deaths from this disease will rise to over 11 million in 2030. Most cases of
      cancer can be cured with surgery, radiotherapy or chemotherapy if they are
      detected at an early stage. However, current cancer therapies are commonly
      associated with undesirable side effects, as most chemotherapy treatments are
      cytotoxic and present poor tumor targeting. AREAS COVERED: Lipid nanoparticles
      (LN) are one of the most promising options in this field. LN are made up of
      biodegradable generally recognized as safe (GRAS) lipids, their formulation
      includes different techniques, and most are easily scalable to industrial
      manufacture. LN overcome the limitations imposed by the need for intravenous
      administration, as they are mainly absorbed via the lymphatic system when they
      are administered orally, which improves drug bioavailability. Furthermore,
      depending on their composition, LN present the ability to cross the blood-brain
      barrier, thus opening up the possibility of targeting brain tumors. EXPERT
      OPINION: The drawbacks of chemotherapeutic agents make it necessary to invest in
      research to find safer and more effective therapies. Nanotechnology has opened
      the door to new therapeutic options through the design of formulations that
      include a wide range of materials and formulations at the nanometer range, which
      improve drug efficacy through direct or indirect tumor targeting, increased
      bioavailability and diminished toxicity.

PMID- 22950879
TI  - A novel antibacterial and antifungal phenolic compound from the endophytic fungus
      Pestalotiopsis mangiferae.
AB  - A novel phenolic compound, 4-(2,4,7-trioxa-bicyclo[4.1.0]heptan-3-yl) phenol (1),
      was isolated from Pestalotiopsis mangiferae, an endophytic fungus associated with
      Mangifera indica Linn. The structure of the compound was elucidated on the basis
      of comprehensive spectral analysis (UV, IR, 1H-, 13C- and 2D-NMR, as well as
      HRESI-MS). Compound (1) shows potent antibacterial and antifungal activity
      against Bacillus subtilis, Klebsiella pneumoniae, Escherichia coli, Micrococcus
      luteus, Pseudomonas aeruginosa and Candida albicans. The transmission electron
      microscope study for the mode of inhibition of compound (1) on bacterial
      pathogens revealed the destruction of bacterial cells by cytoplasm agglutination
      with the formation of pores in cell wall membranes.

PMID- 22950880
TI  - Chemical reactivity and skin sensitization potential for benzaldehydes: can
      Schiff base formation explain everything?
AB  - Skin sensitizers chemically modify skin proteins rendering them immunogenic.
      Sensitizing chemicals have been divided into applicability domains according to
      their suspected reaction mechanism. The widely accepted Schiff base applicability
      domain covers aldehydes and ketones, and detailed structure-activity-modeling for
      this chemical group was presented. While Schiff base formation is the obvious
      reaction pathway for these chemicals, the in silico work was followed up by
      limited experimental work. It remains unclear whether hydrolytically labile
      Schiff bases can form sufficiently stable epitopes to trigger an immune response
      in the living organism with an excess of water being present. Here, we performed
      experimental studies on benzaldehydes of highly differing skin sensitization
      potential. Schiff base formation toward butylamine was evaluated in acetonitrile,
      and a detailed SAR study is presented. o-Hydroxybenzaldehydes such as
      salicylaldehyde and the oakmoss allergens atranol and chloratranol have a high
      propensity to form Schiff bases. The reactivity is highly reduced in p-hydroxy
      benzaldehydes such as the nonsensitizing vanillin with an intermediate reactivity
      for p-alkyl and p-methoxy-benzaldehydes. The work was followed up under more
      physiological conditions in the peptide reactivity assay with a lysine-containing
      heptapeptide. Under these conditions, Schiff base formation was only observable
      for the strong sensitizers atranol and chloratranol and for salicylaldehyde.
      Trapping experiments with NaBH3CN showed that Schiff base formation occurred
      under these conditions also for some less sensitizing aldehydes, but the reaction
      is not favored in the absence of in situ reduction. Surprisingly, the Schiff
      bases of some weaker sensitizers apparently may react further to form stable
      peptide adducts. These were identified as the amides between the lysine residues
      and the corresponding acids. Adduct formation was paralleled by oxidative
      deamination of the parent peptide at the lysine residue to form the peptide
      aldehyde. Our results explain the high sensitization potential of the oakmoss
      allergens by stable Schiff base formation and at the same time indicate a novel
      pathway for stable peptide-adduct formation and peptide modifications by
      aldehydes. The results thus may lead to a better understanding of the Schiff base
      applicability domain.

PMID- 22950881
TI  - Multimorbidity is associated with higher out-of-pocket spending: a study of older
      Australians with multiple chronic conditions.
AB  - Most older Australians have at least one chronic health condition. The management
      of chronic disease is associated with potentially severe economic consequences
      for patients and their households, partially due to the financial burden
      associated with out-of-pocket costs for medical and health-related care. A
      questionnaire was mailed to a cross-sectional sample of older Australians in mid
      2009, with 4574 responding. Multivariate logistic regression models were
      developed to investigate the relationships between multimorbidity and out-of
      pocket spending on medical and health-related expenses, including the factors
      associated with severe financial stress among older Australians. We found a
      positive relationship between number of chronic conditions and out-of-pocket
      spending on health and that people with multiple chronic conditions tend to be on
      lower incomes. People with five or more chronic conditions spent on average five
      times as much on their health as those with no diagnosed chronic conditions and
      each additional chronic disease added 46% to the likelihood of a person facing a
      severe financial burden due to health costs. 

PMID- 22950882
TI  - Biosynthesis of oestrogen by the early equine embryo proper.
AB  - The embryo proper in early equine pregnancy has recently been shown to have a
      remarkable capacity for metabolism of oestrogens. High concentrations of
      oestrogens in yolk-sac fluid could provide substrate for local metabolism in
      tissues of the embryo proper and this activity could have significance for early
      development. Due to the high level of oestrogen metabolism in the embryo proper
      we examined the possibility that it could also biosynthesise oestrogens.
      Conceptuses were collected in the fourth week of pregnancy (n=23) and the embryo
      was separated from extraembryonic tissues for incubation with
      [(3)H]androstenedione. Steroids were recovered from media by solid-phase
      extraction and eluted as unconjugated and conjugated fractions. Profiles of free
      and sulfoconjugated fractions, as well as the phenolic steroids extracted from
      them, were obtained by chromatography. Oestrone and oestradiol were seen clearly,
      indicating oestrogen biosynthesis, and the presence of more polar products,
      arising from metabolism of the primary oestrogens, gave further evidence that the
      embryo was capable of oestrogen biosynthesis. Aromatase activity was also
      demonstrated by detection of tritium loss, as (3)H(2)O, from incubations (n=3)
      with [1beta-(3)H]androstenedione. It is suggested that its oestrogen biosynthesis
      may have significance for the remarkable development of the vasculature in the
      embryo proper at this stage.

PMID- 22950883
TI  - The Pap smear screening as an occasion for smoking cessation and physical
      activity counselling: effectiveness of the SPRINT randomized controlled trial.
AB  - BACKGROUND: The organized Cervical Cancer Screening Programme (CCSP) in Italy
      might represent an occasion to deliver smoking cessation (SC) counselling to
      women attending the Pap test examination. Evidence of effectiveness of physical
      activity (PA) promotion and intervention in adjunct to SC counselling is not
      strong.Objective of the SPRINT trial was to evaluate the effectiveness of a
      standard SC counselling intervention delivered by trained midwives in the CCSP,
      and whether the adjunct of a PA counselling to the SC counselling might increase
      quit rates. METHODS/DESIGN: We undertook a randomized controlled trial of 1,100
      women undergoing the Pap examination in the three study centres Florence, Turin,
      and Mantua: 363 were randomly assigned to the SC counselling arm, 366 to the SC +
      PA counselling arm, and 371 to the control group. The intervention was a standard
      brief SC counselling combined with a brief counselling on increasing PA, and was
      tailored according to the Di Clemente-Prochaska motivational stages of change for
      SC and/or PA. Primary outcomes were quit rates, improvement in the motivational
      stages of change for SC, and reduced daily cigarette consumption. Analysis was by
      intention to treat. RESULTS: Participants randomized in both intervention arms
      and in the preparation stage of change for SC doubled their likelihood of
      quitting at 6-month follow-up in comparison to controls (odds ratio [OR]=2.1, 95%
      confidence interval [95% CI]:1.0-4.6). Moreover, participants in the intervention
      arms and in the contemplation stage were more likely to reduce their daily
      cigarette consumption after the intervention (OR=1.8, 95% CI:1.1-3.0). Our study
      did not show any effect of PA counselling on various outcomes. CONCLUSIONS:
      Smoking cessation counselling delivered by midwives to smokers in preparation and
      contemplation stages of change during the Pap-smear screening was effective and
      should be recommended, given the high number of women attending the cervical
      cancer screening programme in Italy. Moreover, the daily number of women invited
      for the Pap-smear examination should be slightly lowered, in order to let
      midwives deliver SC counselling to smokers. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN52660565.

PMID- 22950884
TI  - Validation of a transparent decision model to rate drug interactions.
AB  - BACKGROUND: Multiple databases provide ratings of drug-drug interactions. The
      ratings are often based on different criteria and lack background information on
      the decision making process. User acceptance of rating systems could be improved
      by providing a transparent decision path for each category. METHODS: We rated 200
      randomly selected potential drug-drug interactions by a transparent decision
      model developed by our team. The cases were generated from ward round
      observations and physicians' queries from an outpatient setting. We compared our
      ratings to those assigned by a senior clinical pharmacologist and by a standard
      interaction database, and thus validated the model. RESULTS: The decision model
      rated consistently with the standard database and the pharmacologist in 94 and
      156 cases, respectively. In two cases the model decision required correction.
      Following removal of systematic model construction differences, the DM was fully
      consistent with other rating systems. CONCLUSION: The decision model reproducibly
      rates interactions and elucidates systematic differences. We propose to supply
      validated decision paths alongside the interaction rating to improve
      comprehensibility and to enable physicians to interpret the ratings in a clinical
      context.

PMID- 22950885
TI  - Reversed phase HPLC analysis of stability and microstructural effects on
      degradation kinetics of beta-carotene encapsulated in freeze-dried maltodextrin
      emulsion systems.
AB  - Degradation of dispersed lipophilic compounds in hydrophilic solids depends upon
      matrix stability and lipid physicochemical properties. This study investigated
      effects of solid microstructure and size of lipid droplets on the stability of
      dispersed beta-carotene in freeze-dried systems. Emulsions of beta-carotene in
      sunflower oil were dispersed in maltodextrin systems (M040/DE6, M100/DE11, and
      M250/DE25.5) (8% w/w oil) and prefrozen at various freezing conditions prior to
      freeze-drying to control nucleation and subsequent pore size and structural
      collapse of freeze-dried solids. The particle size, physical state, and beta
      carotene contents of freeze-dried emulsions were measured during storage at
      various water activity (a(w)) using a laser particle size analyzer, differential
      scanning calorimeter, and high performance liquid chromatography (HPLC),
      respectively. The results showed that M040 stabilized emulsions in low
      temperature freezing exhibited lipid crystallization. Collapse of solids in
      storage at a(w) which plasticized systems to the rubbery state led to flow and
      increased the size of oil droplets. Degradation of beta-carotene analyzed using a
      reversed-phase C(30) column followed first-order kinetics. Porosity of solids had
      a major effect on beta-carotene stability; however, the highest stability was
      found in fully plasticized and collapsed solids.

PMID- 22950886
TI  - Birth of cloned calves from vitrified-warmed zona-free buffalo (Bubalus bubalis)
      embryos produced by hand-made cloning.
AB  - The availability of techniques for the vitrification of cloned blastocysts can
      improve their effective use. The present study compared the developmental
      competence of buffalo cloned embryos derived from adult (BAF), newborn (BNF) and
      fetal fibroblast (BFF) before and after vitrification. Despite similar cleavage
      rates among the three groups, the blastocyst rate was lower for BAF- than BNF-
      and BFF-derived embryos (30.2+/-2.2% vs 41.7+/-1.7% and 39.1+/-2.1%,
      respectively; P<0.01). The total cell number of BNF-derived blastocysts was
      significantly higher (P<0.01) than that of BFF-derived blastocysts, which, in
      turn, was higher (P<0.01) than that of BAF-derived blastocysts. Following
      transfer of vitrified-warmed blastocysts to recipients, no pregnancy was obtained
      with fresh (n=8) or vitrified-warmed (n=18) BAF-derived blastocysts, whereas
      transfer of fresh BNF- (n=53) and BFF-derived (n=32) blastocysts resulted in four
      and three pregnancies, respectively, which aborted within 90 days of gestation.
      The transfer of vitrified-warmed BNF-derived blastocysts (n=39) resulted in the
      live birth of a calf weighing 41kg, which is now 23 months old and has no
      apparent abnormality, whereas the transfer of vitrified-warmed BFF-derived
      blastocysts (n=18) resulted in one live birth of a calf that died within 6h.
      These results demonstrate that cloned buffalo embryos cryopreserved by
      vitrification can be used to obtain live offspring. 

PMID- 22950887
TI  - Shifts of the psychometric function: distinguishing bias from perceptual effects.
AB  - Morgan, Dillenburger, Raphael, and Solomon have shown that observers can use
      different response strategies when unsure of their answer, and, thus, they can
      voluntarily shift the location of the psychometric function estimated with the
      method of single stimuli (MSS; sometimes also referred to as the single-interval,
      two-alternative method). They wondered whether MSS could distinguish response
      bias from a true perceptual effect that would also shift the location of the
      psychometric function. We demonstrate theoretically that the inability to
      distinguish response bias from perceptual effects is an inherent shortcoming of
      MSS, although a three-response format including also an "undecided" response
      option may solve the problem under restrictive assumptions whose validity cannot
      be tested with MSS data. We also show that a proper two-alternative forced-choice
      (2AFC) task with the three-response format is free of all these problems so that
      bias and perceptual effects can easily be separated out. The use of a three
      response 2AFC format is essential to eliminate a confound (response bias) in
      studies of perceptual effects and, hence, to eliminate a threat to the internal
      validity of research in this area.

PMID- 22950888
TI  - Practitioner perceptions of the use of the Triple P - Positive Parenting Program
      with families from culturally diverse backgrounds.
AB  - Parenting programs are effective as a means of preventing and treating child
      emotional and behavioural problems; however, engagement of families from
      culturally diverse populations has been low. The perceptions of practitioners who
      conduct parent consultations with families from culturally diverse backgrounds
      were assessed to examine the perceived suitability of the Triple P - Positive
      Parenting Program. Practitioners rated the program as moderately acceptable.
      Previous training in parenting intervention and years of experience working with
      parents impacted on practitioner ratings, as did the type of practitioner
      profession. Practitioners identified certain barriers to parents' participation
      and preferred traditional face-to-face delivery formats. Practitioner perceptions
      may influence parental access to parenting programs. To enhance parental access
      to parenting interventions, practitioners may require additional training and
      education about parental preferences and evidence based practice.

PMID- 22950889
TI  - Gossypium herbaceam L. extracts ameliorate disequilibrium of IL-1RA/IL-1beta
      ratio to attenuate inflammatory process induced by amyloid beta in rats.
AB  - A chronic inflammatory response possibly mediated by Amyloid beta (Abeta) is
      believed to be a major factor in the pathology of Alzheimer's disease (AD).
      Studies suggest that the mediators of the inflammatory response, which might
      contribute to brain damage, involve cytokines, such as IL-1beta. IL-1beta could
      play an important part in the development of pathologic conditions. There is also
      an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which
      could prevent the actions of IL-1beta by competing for receptor binding without
      inducing any signal transduction. Therefore, the balance of IL-1beta vs IL-1RA is
      a critical parameter in determining not only whether excessive host inflammation
      will occur, but also the degree of subsequent host cell damage and associated
      toxicity. In our previous study, it has been determined that the anti
      inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its
      neuroprotection. However, the effects of GHE on IL-1beta and IL-1RA have not been
      clearly defined in the experimental rat model of AD induced by Abeta. Therefore,
      the current study is performed to evaluate whether GHE could affect the
      disequilibrium of IL-1RA/IL-1beta ratio in the hippocampus of rats after Abeta
      treatment. Subsequently, we further identify that GHE could efficaciously promote
      Akt and GSK3beta phosphorylation, and thereby contribute to IL-1beta release
      decrease as well as a concurrent increase in the level of IL-1RA through NF
      kappaB and MAPK pathways. As a consequence, GHE is potentially beneficial to
      maintain the endogenous IL-1RA/ IL-1beta balance in the hippocampus of rats and
      it might be a potential agent to ameliorate inflammatory process in AD.

PMID- 22950890
TI  - Nanoparticulate X-ray computed tomography contrast agents: from design validation
      to in vivo applications.
AB  - X-ray computed tomography (CT) is one of the most powerful noninvasive diagnostic
      imaging techniques in modern medicine. Nevertheless, the iodinated molecules used
      as CT contrast agents in the clinic have relatively short circulation times in
      vivo, which significantly restrict the applications of this technique in target
      specific imaging and angiography. In addition, the use of these agents can
      present adverse. For example, an adult patient typically receives approximately
      70 mL of iodinated agent (350 mg I/mL) because of iodine's low contrast efficacy.
      Rapid renal clearance of such a large dose of these agents may lead to serious
      adverse effects. Furthermore, some patients are hypersensitive to iodine. 
      Therefore, biomedical researchers have invested tremendous efforts to address
      these issues. Over the past decade, advances in nanoscience have created new
      paradigms for imaging. The unique properties of nanomaterials, such as their
      prolonged circulating half-life, passive accumulation at the tumor sites, facile
      surface modification, and integration of multiple diverse functions into a single
      particle, make them advantageous for in vivo applications. However, research on
      the utilization of nanomaterials for CT imaging has lagged far behind their
      applications for other imaging techniques such as MRI and fluorescence imaging
      because of the challenges in the preparation of cost-effective nanoparticulate CT
      contrast agents with excellent biocompatibility, high contrast efficacy, long in
      vivo circulation time, and long-term colloidal stability in physiological
      environments.  This Account reviews our recent work on the design and in vivo
      applications of nanoparticulate CT contrast agents. By optimizing the contrast
      elements in the nanoparticles according to the fundamental principles of X-ray
      imaging and by employing the surface engineering approaches that we and others
      have developed, we have synthesized several nanoparticulate CT contrast agents
      with excellent imaging performance. For example, a novel Yb-based nanoparticulate
      agent provides enhanced contrast efficacy compared to currently available CT
      contrast agents under normal operating conditions. To deal with special
      situations, we integrated both Ba and Yb with great differential in K-edge value
      into a single particle to yield the first example of binary contrast agents. This
      agent displays much higher contrast than iodinated agents at different voltages
      and is highly suited to diagnostic imaging of various patients. Because of their
      prolonged in vivo circulation time and extremely low toxicity, these agents can
      be used for angiography.

PMID- 22950891
TI  - Stereocontrolled intramolecular iron-mediated diene/vinyl ether cyclocoupling
      reactions.
AB  - A stereocontrolled intramolecular iron-mediated diene/olefin cyclocoupling
      reaction has been explored using vinyl ethers as the olefin partners.
      Spirolactams with functionalized (alkoxymethyl) side chains can be formed under
      thermal conditions. With a methoxy substituent on the diene, demetalation and
      hydrolysis of the cyclocoupling product afforded a single diastereomer.

PMID- 22950892
TI  - Ultrafast intramolecular charge separation in a donor-acceptor assembly
      comprising bis(eta5-cyclopentadienyl)molybdenum coordinated to an ene-1,2
      dithiolate-naphthalenetetracarboxylicdiimide ligand.
AB  - The first example of a Donor-spacer-Acceptor tryad, based upon a molybdenum-ene
      1,2-dithiolate unit as the Donor and a naphthalene-diimide as the Acceptor, has
      been synthesized and its photophysical properties investigated. Synthesis
      required the preparation of a new pro-ligand containing a protected ene-1,2
      dithiolate bound through a phenyl linkage to a naphthalenetetracarboxylicdiimide
      (NDI) group. Deprotection of this pro-ligand by base hydrolysis, followed by
      reaction with [Cp(2)MoCl(2)], produced the new dyad [Cp(2)Mo(SC(H)C(C(6)H(4)
      NDI)S)] (2). Electrochemical studies showed that 2 can be reversibly oxidized to
      [2](+) and reduced to [2](-), [2](2-), and [2](3-). These studies, augmented by
      UV/vis, IR, and electron paramagnetic resonance (EPR) spectra of
      electrochemically generated [2](+) and [2](-), show that the highest occupied
      molecular orbital (HOMO) of 2 is ene-1,2-dithiolate-based and the lowest
      unoccupied molecular orbital (LUMO) is NDI-based; these conclusions are supported
      by density functional theory (DFT) calculations for the electronic ground state
      on a model of 2 which also showed that these two parts of the molecule are
      electronically distinct. The dynamics of the excited states of 2 in CH(2)Cl(2)
      solution were investigated by picosecond time-resolved IR spectroscopy following
      irradiation by a 400 nm ~120 fs laser pulse. These investigations were
      complemented by an ultrafast transient absorption spectroscopic study from 420 to
      760 nm of the nature of the excited states of 2 in CH(2)Cl(2) solution following
      irradiation by a 383 nm ~120 fs laser pulse. These studies showed that
      irradiation of 2 at both 400 and 383 nm leads to the formation of the
      [(Cp)(2){Mo(dt)}(+)-Ph-{NDI}(-)] charge-separated state as a result of a cascade
      electron transfer initiated by the formation of an (1)NDI* excited state. (1)NDI*
      rapidly (ca. 0.2 ps) forms the local charge transfer state [Cp(2)Mo(dt)-{Ph}(+)
      {NDI}(-)] which has a lifetime of about 1.7 ps and decays to produce the ground
      state and the charge-separated state [(Cp)(2){Mo(dt)}(+.)-Ph-{NDI}(-)]; the
      latter has an appreciable lifetime, about 15 ns in CH(2)Cl(2) at room
      temperature.

PMID- 22950893
TI  - Drop motion induced by repeated stretching and relaxation on a gradient surface
      with hysteresis.
AB  - The motion of a droplet can be induced by periodically compressing and extending
      it between two similar gradient surfaces possessing significant wetting
      hysteresis. The shape fluctuation of the drop during repeated compression
      extension cycles leads to its ratchetlike motion toward the region of higher
      wettability. A simple model requiring the volume preservation of the drop during
      the compression-extension cycles is sufficient to account for the effect and
      predict drop velocity across the surface when drop size and cycle frequency are
      specified. In connection with this study, we also report a variation of the
      standard vapor phase adsorption method of preparing a chemically graded surface
      that allows for good control over the steepness and the length of the active
      zone. The method can be used to produce a linear or a radial gradient, both of
      which are employed here to drive droplet motion along these patterns. This type
      of discrete droplet motion can be used to move drops on surfaces to transport
      materials within miniaturized digital fluidic devices.

PMID- 22950894
TI  - Do rural primary health care nurses feel equipped for palliative care?
AB  - Community primary health care nurses in rural and remote settings are required to
      provide palliative care as part of their generalist role. They have limited
      access to specialist medical and nursing support and sometimes there are no
      resident GPs. A study consisting of a mailed survey and follow-up interviews was
      conducted to explore the experiences of these nurses and to determine how
      personally and professionally equipped they felt for palliative care service
      provision. Most participants were registered nurses experienced in nursing and in
      rural and remote settings, who juggled multiple generalist work roles. They had
      only occasional palliative care patients, and more than half had provided
      palliative care for a friend or family member. Some nurses found palliative care
      rewarding, others preferred not to have to do it. However, even those who did not
      enjoy working with palliative care patients often went beyond the 'call of duty'
      to support a home death if that was what the patient wanted. Three-quarters had
      attended palliative care education in the last 2 years but 88% wanted more
      education. Barriers to education included competing work roles, work load,
      geographical isolation and lack of backfill. Support from managers and peers was
      considered important, as was accessing timely and relevant clinical support.

PMID- 22950895
TI  - Barbiturates use and its effects in patients with severe traumatic brain injury
      in five European countries.
AB  - The guidelines for management of traumatic brain injury (TBI) recommend that high
      dose barbiturate therapy may be considered to lower intracranial pressure (ICP)
      that is refractory to other therapeutic options. Lower doses of barbiturates may
      be used for sedation of patients with TBI, although there is no mention of this
      in the published guidelines. The goal of this study was to analyze the use of
      barbiturates in patients with severe TBI in the European centers where the
      International Neurotrauma Research Organization introduced guideline-based TBI
      management and to analyze the effects of barbiturates on ICP, use of
      vasopressors, and short- and long-term outcome of these patients. Data on 1172
      patients with severe TBI were collected in 13 centers located in five European
      countries. Patients were categorized into three groups based on doses of
      barbiturates administered during treatment. Univariate and multivariate
      statistical methods were used to analyze the effects of barbiturates on the
      outcome of patients. Fewer than 20% of all patients with severe TBI were given
      barbiturates overall, and only 6% was given high doses. High-dose barbiturate
      treatment caused a decrease in ICP in 69% of patients but also caused hemodynamic
      instability leading to longer periods of mean arterial pressure <70 mm Hg despite
      increased use of high doses of vasopressors. The adjusted analysis showed no
      significant effect on outcome on any stage after injury.Thiopental and
      methohexital were equally effective. Low doses of thiopental and methohexital
      were used for sedation of patients without side effects. Phenobarbital was
      probably used for prophylaxis of post-traumatic seizures.

PMID- 22950896
TI  - Health and demographic surveillance systems: a step towards full civil
      registration and vital statistics system in sub-Sahara Africa?
AB  - BACKGROUND: In the developed world, information on vital events is routinely
      collected nationally to inform population and health policies. However, in many
      low-and middle-income countries, especially those in sub-Saharan Africa (SSA),
      there is a lack of effective and comprehensive national civil registration and
      vital statistics system. In the past decades, the number of Health and
      Demographic Surveillance Systems (HDSSs) has increased throughout SSA. An HDSS
      monitors births, deaths, causes of death, migration, and other health and socio
      economic indicators within a defined population over time. Currently, the
      International Network for the Continuous Demographic Evaluation of Populations
      and Their Health (INDEPTH) brings together 38 member research centers which run
      44 HDSS sites from 20 countries in Africa, Asia and Oceana. Thirty two of these
      HDSS sites are in SSA. DISCUSSION: This paper argues that, in the absence of an
      adequate national CRVS, HDSSs should be more effectively utilised to generate
      relevant public health data, and also to create local capacity for longitudinal
      data collection and management systems in SSA. If HDSSs get strategically located
      to cover different geographical regions in a country, data from these sites could
      be used to provide a more complete national picture of the health of the
      population. They provide useful data that can be extrapolated for national
      estimates if their regional coverage is well planned. HDSSs are however resource
      intensive. Efforts are being put towards getting them linked to local or national
      policy contexts and to reduce their dependence on external funding. Increasing
      their number in SSA to cover a critical proportion of the population, especially
      urban populations, must be carefully planned. Strategic planning is needed at
      national levels to geographically locate HDSS sites and to support these through
      national funding mechanisms. SUMMARY: The paper does not suggest that HDSSs
      should be seen as a replacement for civil registration systems. Rather, they
      should serve as a short- to medium-term measure to provide data for health and
      population planning at regional levels with possible extrapolation to national
      levels. HDSSs can also provide useful lessons for countries that intend to set up
      nationally representative sample vital registration systems in the long term.

PMID- 22950897
TI  - Quantitative detection of IDH2 mutation for minimal residual disease monitoring
      in patients with acute myeloid leukemia and its comparison with mutations in NPM1
      gene.

PMID- 22950898
TI  - Photochemotherapeutic strategies against Acanthamoeba keratitis.
AB  - Here, we determined the potential of photochemotherapy, namely the application
      of photodynamic compounds followed by exposure to a suitable source of UV-visible
      radiation against corneal pathogen, Acanthamoeba. Organometallic macromolecule,
      tin porphyrin [Sn(IV)porphyrin] was synthesized and purity confirmed using
      nuclear magnetic resonance spectroscopy. The Sn(IV)porphyrin was tested against a
      keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype using
      growth and viability assays. The effects of Sn(IV)porphyrin on A. castellanii
      binding to and cytopathogenicity of human corneal epithelial cells in vitro were
      tested. The metalloporphyrin showed potent amoebistatic effects. The tin
      porphyrin inhibited amoebae binding to and cytopathogenicity of corneal
      epithelial cells. By using derivatives of photodynamic compounds [Sn(IV)porphyrin
      antibody conjugates] for selective targeting of the parasite together with
      appropriate selection of light source will determine the potential of
      photochemotherapy against Acanthamoeba keratitis.

PMID- 22950899
TI  - Sequence variations in OsAGPase significantly associated with amylose content and
      viscosity properties in rice (Oryza sativa L.).
AB  - Sequence-based variations in starch synthesis-related genes (SSRGs) exert a basic
      influence on the determination of eating quality in rice (Oryza sativa L.). This
      study aimed to investigate the relationship between the sequence variations from
      parts of 10 SSRGs and the amylose content (AC) plus rapid viscosity analysis
      (RVA) profiles in a heuristic rice core set by association mapping (AM). In
      total, 86 sequence variations were found in 10 sequenced amplicons, including 79
      single-nucleotide polymorphisms (SNPs), six insertion-deletions (InDels) and one
      polymorphic simple sequence repeat (SSR). Among them, 61 variations were exon
      based, of which 41 should lead to amino acid changes. Four subpopulations were
      revealed by population structure analysis based on 170 genome-wide SSR genotypes.
      The final AM showed a sum of four significant associations between three
      phenotypic indices and three sequence variations. An ADP-glucose
      pyrophosphorylase small unit 1 (OsAGPS1) SNP (A-G) was significantly associated
      with increased AC (P<0.001, R(2)=15.6%), while a 12-bp deletion of AGPase large
      unit 4 (OsAGPL4) was significantly related to the decreased breakdown viscosity
      (BDV) (P<0.001, R(2)=16.6%) in both general linear model (GLM) and mixed linear
      model (MLM). This study provides a new perspective of allele mining for breeding
      strategies based on marker-assisted selection.

PMID- 22950900
TI  - Comparing linkage and association analyses in sheep points to a better way of
      doing GWAS.
AB  - Genome wide association studies (GWAS) have largely succeeded family-based
      linkage studies in livestock and human populations as the preferred method to map
      loci for complex or quantitative traits. However, the type of results produced by
      the two analyses contrast sharply due to differences in linkage disequilibrium
      (LD) imposed by the design of studies. In this paper, we demonstrate that
      association and linkage studies are in agreement provided that (i) the effects
      from both studies are estimated appropriately as random effects, (ii) all markers
      are fitted simultaneously and (iii) appropriate adjustments are made for the
      differences in LD between the study designs. We demonstrate with real data that
      linkage results can be predicted by the sum of association effects. Our
      association study captured most of the linkage information because we could
      predict the linkage results with moderate accuracy. We suggest that the ability
      of common single nucleotide polymorphism (SNP) to capture the genetic variance in
      a population will depend on the effective population size of the study organism.
      The results provide further evidence for many loci of small effect underlying
      complex traits. The analysis suggests a more informed method for GWAS is to fit
      statistical models where all SNPs are analysed simultaneously and as random
      effects.

PMID- 22950901
TI  - Gene network-based cancer prognosis analysis with sparse boosting.
AB  - High-throughput gene profiling studies have been extensively conducted, searching
      for markers associated with cancer development and progression. In this study, we
      analyse cancer prognosis studies with right censored survival responses. With
      gene expression data, we adopt the weighted gene co-expression network analysis
      (WGCNA) to describe the interplay among genes. In network analysis, nodes
      represent genes. There are subsets of nodes, called modules, which are tightly
      connected to each other. Genes within the same modules tend to have co-regulated
      biological functions. For cancer prognosis data with gene expression
      measurements, our goal is to identify cancer markers, while properly accounting
      for the network module structure. A two-step sparse boosting approach, called
      Network Sparse Boosting (NSBoost), is proposed for marker selection. In the first
      step, for each module separately, we use a sparse boosting approach for within
      module marker selection and construct module-level 'super markers'. In the second
      step, we use the super markers to represent the effects of all genes within the
      same modules and conduct module-level selection using a sparse boosting approach.
      Simulation study shows that NSBoost can more accurately identify cancer
      associated genes and modules than alternatives. In the analysis of breast cancer
      and lymphoma prognosis studies, NSBoost identifies genes with important
      biological implications. It outperforms alternatives including the boosting and
      penalization approaches by identifying a smaller number of genes/modules and/or
      having better prediction performance.

PMID- 22950902
TI  - Fine-mapping quantitative trait loci with a medium density marker panel:
      efficiency of population structures and comparison of linkage disequilibrium
      linkage analysis models.
AB  - Recently, a Haley-Knott-type regression method using combined linkage
      disequilibrium and linkage analyses (LDLA) was proposed to map quantitative trait
      loci (QTLs). Chromosome of 5 and 25 cM with 0.25 and 0.05 cM, respectively,
      between markers were simulated. The differences between the LDLA approaches with
      regard to QTL position accuracy were very limited, with a significantly better
      mean square error (MSE) with the LDLA regression (LDLA_reg) in sparse map cases;
      the contrary was observed, but not significantly, in dense map situations. The
      computing time required for the LDLA variance components (LDLA_vc) model was much
      higher than the LDLA_reg model. The precision of QTL position estimation was
      compared for four numbers of half-sib families, four different family sizes and
      two experimental designs (half-sibs, and full- and half-sibs). Regarding the
      number of families, MSE values were lowest for 15 or 50 half-sib families,
      differences not being significant. We observed that the greater the number of
      progenies per sire, the more accurate the QTL position. However, for a fixed
      population size, reducing the number of families (e.g. using a small number of
      large full-sib families) could lead to less accuracy of estimated QTL position.

PMID- 22950903
TI  - Extreme weather-related health needs of people who are homeless.
AB  - To identify the extreme weather-related health needs of homeless people and the
      response by homeless service providers in Adelaide, South Australia, a five
      phased qualitative interpretive study was undertaken. (1) Literature review,
      followed by semi-structured interviews with 25 homeless people to ascertain
      health needs during extreme weather events. (2) Identification of homeless
      services. (3) Semi-structured interviews with 16 homeless service providers
      regarding their response to the health needs of homeless people at times of
      extreme weather. (4) Gap analysis. (5) Suggestions for policy and planning.
      People experiencing homelessness describe adverse health impacts more from
      extreme cold, than extreme hot weather. They considered their health suffered
      more, because of wet bedding, clothes and shoes. They felt more depressed and
      less able to keep themselves well during cold, wet winters. However, homeless
      service providers were more focussed on planning for extra service responses
      during times of extreme heat rather than extreme cold. Even though a city may be
      considered to have a temperate climate with a history of very hot summers,
      primary homeless populations have health needs during winter months. The
      experiences and needs of homeless people should be considered in extreme weather
      policy and when planning responses. 

PMID- 22950905
TI  - Understanding the impact of Schottky barriers on the performance of narrow
      bandgap nanowire field effect transistors.
AB  - Semiconductor nanowires have been explored as alternative electronic materials
      for high performance device applications exhibiting low power consumption specs.
      Electrical transport in III-V nanowire (NW) field-effect transistors (FETs) is
      frequently governed by Schottky barriers between the source/drain and the NW
      channel. Consequently the device performance is greatly impacted by the contacts.
      Here we present a simple model that explains how ambipolar device characteristics
      of NW-FETs and in particular the achievable on/off current ratio can be analyzed
      to gain a detailed idea of (a) the bandgap of the synthesized NWs and (b) the
      potential performance of various NW materials. In particular, we compare the
      model with our own transport measurements on InSb and InAs NW-FETs as well as
      results published by other groups. The analysis confirms excellent agreement with
      the predictions of the model, highlighting the potential of our approach to
      understand novel NW based materials and devices and to bridge material
      development and device applications.

PMID- 22950904
TI  - The impact of visa status and Medicare eligibility on people diagnosed with HIV
      in Western Australia: a qualitative report.
AB  - BACKGROUND: In Australia, temporary visa holders are ineligible for Medicare and
      subsidised antiretroviral drugs. Additionally, HIV testing is not mandatory for
      visas unless applicants seek work in the health sector. We sought to understand
      the impact of HIV and issues of access and adherence to antiretroviral therapy
      (ART) in people holding temporary visas and permanent residents. METHODS: Data
      were gathered from interviews with 22 participants. Information concerning
      medication adherence, side effects, CD4 T-cell count, viral load and rate of
      response to generic drugs were collected. RESULTS: The mean age was 33.4 years
      (+/-s.d.=6.0), 21 out of 22 were from HIV-prevalent areas in East Africa and
      Asia, 14 out of 22 were on temporary visas, 12 were ineligible for Medicare, 14
      out of 22 were diagnosed during health screening, 19 out of 22 risk exposures
      were in country of origin, 8 out of 17 were taking generic ART at an average cost
      of $180 per month, adherence was excellent and self-reported side-effects were
      relatively infrequent. Participants applying for visa continuations and permanent
      residency were fearful, believing their HIV serostatus would prejudice their
      applications. Patients cited belief in ART efficacy, were motivated to maintain
      therapy and were anxious about lack of access to treatment in their countries of
      origin. CONCLUSION: Adherence to antiretroviral drugs in Medicare-ineligible HIV
      infected individuals is excellent despite limited access to treatment. The threat
      of visa non-renewal and the likely failure of applications for permanent
      residency result in considerable anxiety and confidentiality concerns.

PMID- 22950906
TI  - The Healthy Lifestyle Scale for University Students: development and psychometric
      testing.
AB  - We report the development and validation of a scale to evaluate the healthy
      lifestyles of university students. The Delphi technique was used to determine the
      content validity of the scale with a panel of33 experts. Psychometric testing was
      performed and confirmed with 6000 undergraduate students who were randomly
      selected from 10 universities in China. Three Delphi rounds were required to
      achieve final consensus for content validity. The split-half correlation
      coefficient and Cronbach's alpha coefficient for the total scale were 0.841 and
      0.892, respectively. Construct validity was supported by exploratory factor
      analysis, which yielded an eight-factor instrument that explained 55.02% of the
      variance in the 38 items. The proposed Healthy Lifestyle Scale for University
      Students has good construct validity and reliability and can be used as an
      evaluation tool for health counselling in university health centres.

PMID- 22950907
TI  - Unravelling the needs of singly in vitro-produced bovine embryos: from cumulus
      cell co-culture to semi-defined, oil-free culture conditions.
AB  - Producing bovine in vitro embryos individually is a challenge as it generally
      leads to impaired embryo development. Earlier research optimised a single embryo
      in vitro production (IVP) protocol using serum, cumulus cells and oil during
      culture. As some of these factors are undesirable in certain circumstances, the
      present study investigated their necessity and possible interactions, and defined
      their role during single-embryo culture. Although the cumulus cell monolayer
      produced progesterone, it appeared not to be a key factor in supporting single
      embryo development. Because in vitro culture in large medium volumes was shown to
      impair single-embryo development, two new oil-free culture protocols were tested.
      Using a 30-uL droplet of medium in 96-well plates with a small surface area
      resulted in comparable blastocyst rates to those obtained under oil. When serum
      was used, co-culture with cumulus cells seems necessary, leading to consistently
      high blastocyst rates. Finally, a serum-free, oil-free culture system using
      insulin, transferrin, selenium and BSA resulted in embryos with similar total
      cell numbers and apoptotic cell ratios, but blastocyst rates did not equal those
      obtained with serum and co-culture. This research additionally stresses the fact
      that specific interaction mechanisms between somatic cells and a developing in
      vitro embryo are far from unravelled.

PMID- 22950908
TI  - Memory of chirality of tertiary aromatic amide: application to the asymmetric
      synthesis of (S)-alpha-methylDOPA.
AB  - We describe an original asymmetric synthesis of (S)-alpha-methylDOPA proceeding
      by the concept of memory of chirality, the only source of chirality being the
      starting D-alanine. The initial chirality of the amino acid is temporarily
      transferred to a dynamic axial chirality of a tertiary aromatic amide. The (S)
      alpha-methylDOPA hydrochloride is obtained after four steps with 98% ee.

PMID- 22950909
TI  - Brain environment and Alzheimer's disease mutations affect the survival,
      migration and differentiation of neural progenitor cells.
AB  - Enhancement of neurogenesis and stem cell transplantation are potential therapies
      for neurodegenerative diseases. In Alzheimer's disease (AD) newborn neural cells
      and the transplanted cells encounter a diseased brain where the accumulation of
      toxic amyloid-beta (Abeta) peptides disturbs normal functions and interactions of
      brain cells. In addition, ADlinked mutatations in newborn neurons or autologously
      transplanted neural progenitor cells (NPCs) are likely to affect the fate of
      these cells. Here we analyzed the effect of AD-linked APdE9 mutant on NPCs in
      culture and by isolating NPCs from APdE9 transgenic mice and transplanting them
      into APdE9 and wild type mouse brain. We show that the brain environment in APdE9
      mutant mice reduced astrocytic differentiation but increased the survival and
      migration of NPCs in vivo. APdE9 mutation of NPCs increased neuronal
      differentiation also in vitro. Instead extracellular Abeta(42) peptide decreased
      the survival, neuronal differentiation and migration of NPCs in vitro, whereas
      Abeta(40) had an opposite effect. NPC transplantation induced brain neurogenesis,
      which was not altered in Abeta burdened APdE9 brain or by APdE9 mutant in NPCs.
      Thus, AD-linked mutations in newborn neural cells or NPCs do not compromise the
      utilization of enhanced neurogenesis or autologous NPC transplantation as
      potential therapies. The results suggest that combining the treatments resulting
      in reduced Abeta(42) and enhanced neurogenesis may be one therapeutic approach to
      be explored in AD.

PMID- 22950910
TI  - Intracellular accumulation of toxic turn amyloid-beta is associated with
      endoplasmic reticulum stress in Alzheimer's disease.
AB  - Amyloid-beta protein (Abeta) accumulates in the neurons of Alzheimer's disease
      (AD) patients at an early stage of the disease. Recently, we found that Abeta
      with a toxic turn at positions 22 and 23 accumulates in neurons in AD brain.
      Here, we studied the accumulation of Abeta, toxic turn Abeta and high-molecular
      weight Abeta oligomers in presenilin 1 (PS1) gene-transfected SH-SY5Y cells as
      well as in the brains of 3xTg-AD mice and AD patients. Immunostaining revealed
      that accumulation of toxic turn Abeta was promoted in G384A- and I143T-mutant PS1
      transfected cells and further enhanced by co-transfection of cells with the Abeta
      precursor protein (AbetaPP) gene. In contrast, accumulation of high-molecular
      weight Abeta oligomers was promoted in mutant PS1 cells but attenuated by co
      transfection of cells with the AbetaPP gene. Toxic turn Abeta was detected in the
      neurons of 3xTg-AD mice aged 2 months, when the mice were cognitively unimpaired.
      In contrast, high-molecular-weight Abeta oligomers were detected in the neurons
      of 7-month-old mice, when memory dysfunction is apparent. Furthermore,
      immunostaining and western blotting for Rab4, Rab6 and GRP78 revealed increased
      levels of these proteins in mutant PS1 cells and their accumulation in the
      neurons of 3xTg-AD mice. Remarkably, GRP78 immunoreactivity was increased at 2
      months of age. Double-label immunostaining of AD brain revealed an apparent
      association between toxic turn Abeta and GRP78, an endoplasmic reticulum (ER)
      stress marker. Intraneuronal accumulation of toxic turn Abeta may be associated
      with ER stress in the brains of AD model mice and AD patients at an early stage.

PMID- 22950911
TI  - Therapeutic effects of quetiapine on memory deficit and brain beta-amyloid plaque
      pathology in a transgenic mouse model of Alzheimer's disease.
AB  - Our previous study has shown the preventive effects of quetiapine, an atypical
      antipsychotic drug, on memory impairment and brain pathological changes in a
      mouse model of Alzheimer's disease (AD). The aim of the present study was to
      evaluate the therapeutic effects of quetiapine on memory deficit and
      neuropathology in an amyloid precursor protein (APP)/presenilin-1 (PS1) double
      transgenic mouse model of AD. The APP/PS1 mice started to have detectable brain
      beta-amyloid (Abeta) at 3 months of age. Non-transgenic and transgenic mice were
      treated with quetiapine (0, 2.5, or 5 mg/(kg day)) in drinking water from the age
      of 4 months. After 8 months of continuous quetiapine administration, memory
      deficit was reversed and brain Abeta plaque pathology was attenuated in the AD
      mice. Quetiapine also decreased the soluble Abeta peptide levels in brain and
      cerebrospinal fluid (CSF), and attenuated the decreased synaptic protein levels
      in the AD mice. Furthermore, quetiapine normalized the abnormal activity of
      glycogen synthase kinase-3beta (GSK-3beta), an AD-involved kinase, in the AD
      mice. These results suggest that quetiapine can treat and alleviate the
      neuropathology in an APP/PS1 transgenic mouse model of AD, and indicate that
      quetiapine may have therapeutic effects in the treatment of AD.

PMID- 22950912
TI  - Systemic oxidative stress in older patients with mild cognitive impairment or
      late onset Alzheimer's disease.
AB  - A large body of evidences obtained in human and animal brain tissue suggest a
      role of oxidative stress (OxS) in the pathogenesis of late onset Alzheimer's
      disease (LOAD); on the contrary, data on peripheral markers of OxS in LOAD are
      still controversial. We evaluated the serum levels of products of lipid
      peroxidation, hydroperoxides, advanced oxidation protein products, total and
      residual antioxidant power, thiols, and uric acid in a sample of 334 older
      individuals: 101 LOAD patients, 134 patients with mild cognitive impairment
      (MCI), and 99 controls. At univariate analysis, serum hydroperoxides were higher
      while residual antioxidant power was lower in MCI and LOAD compared with in
      controls. By multivariate logistic regression analysis we found that, compared
      with controls, high levels (over median value) of serum hydroperoxides were
      independently associated with an increase in the likehood of having MCI (Odd
      Ratio: 2.59, 95% Confidence Interval: 1.08-6.21) or LOAD (OR: 4.09, 95%CI: 1.36
      11.81). Furthermore, low levels of residual antioxidant power (below the median
      value) were associated with increased risk of having MCI (OR: 3.97, 95% CI: 1.62
      9.72), but not dementia (OR: 2.31, 95%CI: 0.83-6.63). Our study suggests that a
      systemic redox-imbalance leading to OxS might be associated not only with LOAD
      but also with MCI.

PMID- 22950913
TI  - Lipid rafts mediate amyloid-induced calcium dyshomeostasis and oxidative stress
      in Alzheimer's disease.
AB  - Several lines of evidence suggest that the initial events of amyloid-beta peptide
      (Abeta) oligomerization and deposition in Alzheimer's disease (AD) involve the
      interaction of soluble oligomers with neuronal membranes. In this study, we show
      that Abeta42 oligomers are recruited to lipid rafts, which are ordered membrane
      microdomains rich in cholesterol and gangliosides, resulting in lipid
      peroxidation, Ca(2+) dyshomeostasis and membrane permeabilization in primary
      fibroblasts from familial AD patients (FAD) bearing APPVal717Ile, PS-1Leu392Val
      or PS-1Met146Leu gene mutations. Moreover, the presence of significantly higher
      levels of lipid peroxidation correlated with greater structural modification in
      detergent resistant domains (DRMs) isolated from APP and PS-1 fibroblasts,
      compared to WT fibroblasts from healthy subjects. Modulation of raft GM1,
      including modest depletion of GM1 content and interference with GM1 exposure or
      negative charge, precluded the interaction of amyloid aggregates with the plasma
      membrane and the resulting cell damage in FAD fibroblasts and rat brains cortical
      neurons. These findings suggest a specific role for raft domains as primary
      mediators of amyloid toxicity in AD neurons.

PMID- 22950914
TI  - Quetiapine modulates conditioned anxiety and alternation behavior in Alzheimer's
      transgenic mice.
AB  - Quetiapine, an atypical antipsychotic drug, is effective in treating the
      behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is
      presently unclear whether quetiapine has beneficial effects on memory and whether
      the effects of quetiapine on psychological symptoms are associated with its
      effect on memory in AD. The present study was designed to examine the effect of
      chronic administration of quetiapine on the conditioned (generalized) anxiety
      that is related to learning experience of open arm exposure in the elevated T
      maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double
      transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on
      memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and
      transgenic mice were treated with quetiapine in drinking water from the age of 2
      months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months,
      mice were tested for conditioned anxiety on the ETM task. After ETM testing, the
      expression of brain-derived neurotrophic factor (BDNF), a neuroprotective
      protein, was examined by immunohistochemistry in the basolateral amygdala (BLA)
      and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5
      mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After
      10 months of administration, quetiapine prevented the decrease of conditioned
      anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented
      memory impairment in the Y-maze test in AD mice. These findings suggest that the
      therapeutic mechanism of quetiapine on anxiety in AD may be associated with its
      beneficial effect on memory and its neuroprotective effect on cerebral BDNF
      expression.

PMID- 22950915
TI  - Antipsychotic use and mortality risk in community-dwelling Alzheimer's disease
      patients: evidence for a role of dementia severity.
AB  - Antipsychotics are widely used for the treatment of behavioral and psychological
      symptoms of dementia (BPSD). Concerns have been raised in the literature over the
      safety of antipsychotics, with suggestions of an increased risk of mortality. The
      objective of this study was to determine the all-cause mortality risk associated
      with antipsychotic use among Alzheimer's disease (AD) patients. A new-user study
      was conducted in a multicentric prospective cohort, composed of 534 community
      dwelling mild-to-moderate AD patients recruited in 16 French memory centers. A
      survival analysis using a Cox proportional hazards model assessed hazard ratios
      (HRs) for death according to either first or second generation antipsychotic use
      (time-varying variable). Among the 534 patients, 102 new users were identified
      throughout the 3.5 year-follow-up period and 113 deaths occurred. The main
      antipsychotics used were risperidone and tiapride. Unadjusted and
      sociodemographic-adjusted (age, gender, center) analyses suggested an increased
      risk of death with antipsychotic use (HR: 1.84; 95% CI: [1.09-3.09] and HR: 1.93;
      95% CI: [1.15-3.25]) respectively). However, antipsychotic use did not appear to
      be an independent predictive factor of death when dementia severity (cognitive
      status) was accounted for during fully adjusted multivariate analyses (HR: 1.12;
      95% CI: [0.59-2.12]). Antipsychotic use may be associated with an increased risk
      of mortality, but to a lesser extent than several other factors which were found
      to be significant predictors of mortality (age, male gender, cognitive score,
      recent hospitalisation, medical aid). To date, antipsychotic risks outweigh their
      benefits in BPSD for which non-pharmacological approaches remain the first-line
      strategy and should be privileged.

PMID- 22950916
TI  - Morphology of twin and triplet equine conceptuses during weeks 3 and 4 of
      pregnancy.
AB  - Twin ovulations are common in horses, but twin pregnancies are rarely carried to
      term. Theories of how one or both twins is/are naturally eliminated in early
      pregnancy, termed 'embryo reduction', have been based on ultrasonographic, not
      morphological, studies. Here we describe conceptuses recovered transcervically
      between Days 15 and 28 from 31 twin and two triplet pregnancies. Signs of contact
      between conceptuses were deduced from those seen in one pair that remained
      attached by their capsules on Day 18. Signs were found on capsules in two of 10
      pairs before or during fixation (immobilisation) at Days 16-17 even though
      contact had not been seen by ultrasound. After fixation, the signs became
      stronger in seven of nine unilateral pregnancies, indicated adhesion between
      pairs and included effects on the vitelline circulation and/or degeneration of
      one twin. Conceptuses recovered from five of seven unilateral twin pregnancies
      after the time of capsule disruption (~Day 21) evidenced embryo reduction; in the
      two surviving pairs, attachment between twins was near the trilaminar/bilaminar
      yolk-sac wall border. The findings are consistent with the notions that: (1) the
      capsule plays a role in initiating adhesion between twins; and (2) twin survival
      depends on an unencumbered trilaminar yolk-sac wall and a functional vitelline
      circulation.

PMID- 22950917
TI  - Large-scale synthesis of lipid-polymer hybrid nanoparticles using a multi-inlet
      vortex reactor.
AB  - Lipid-polymer hybrid nanoparticles combine the advantages of both polymeric and
      liposomal drug carriers and have shown great promise as a controlled drug
      delivery platform. Herein, we demonstrate that it is possible to adapt a multi
      inlet vortex reactor (MIVR) for use in the large-scale synthesis of these hybrid
      nanoparticles. Several parameters, including formulation, polymer concentration,
      and flow rate, are systematically varied, and the effects of each on nanoparticle
      properties are studied. Particles fabricated from this process display
      characteristics that are on par with those made on the lab-scale such as small
      size, low polydispersity, and excellent stability in both PBS and serum. Using
      this approach, production rates of greater than 10 g/h can readily be achieved,
      demonstrating that use of the MIVR is a viable method of producing hybrid
      nanoparticles in clinically relevant quantities.

PMID- 22950919
TI  - Relationships between physical activity and awareness and treatment status among
      adults with low femoral bone density in the United States.
AB  - PURPOSE: To examine relationships between physical activity (PA) and awareness
      and treatment status of low bone mineral density (BMD) among adults. DESIGN:
      Cross-sectional. SETTING: Stratified sample of adults living independently in the
      community. SUBJECTS: A total of 1928 adults aged 50 years and older who
      participated in the National Health and Nutrition Examination Survey 2005-2006
      were included in the analysis. Among those, about 54% were women, 84% were non
      Hispanic whites, 65% were married, and 44% were between 50 and 59 years of age.
      MEASURES: Objective measures: femoral neck BMD and duration of PA and step counts
      measured by accelerometers. Self-report: strength exercise, and awareness and
      treatment of low bone density. ANALYSIS: Multivariate regression analyses using
      SUDAAN. RESULTS: Despite a high prevalence of low BMD, self-reported awareness,
      treatment, and PA were very low. After controlling socio-demographic and health
      related factors, those who were aware of their low bone density status and who
      received treatment for it were less physically active than those who were unaware
      of their bone condition or who did not have any treatment. CONCLUSIONS: PA levels
      are below the recommended level for bone health benefits. Health care providers
      should consider screening individuals at risk of low bone density and encourage
      them to implement prevention and treatment regimen including increasing daily
      levels of PA.

PMID- 22950920
TI  - Participation in community-originated interventions is associated with positive
      changes in weight status and health behaviors in youth.
AB  - PURPOSE: To assess changes in children's health behaviors and weight status after
      participation in community-originated interventions. DESIGN: Prospective cohort
      study following body mass index (BMI) z-score trajectory over time. SETTING:
      Schools and community settings in 19 locations in North Carolina. SUBJECTS: A
      total of 1144 children, with an average age of 9.5 years, participating in
      community-originated physical activity and nutrition interventions, such as
      active recess and healthy cafeteria offerings, and environment and policy changes
      designed to prevent and reduce the prevalence of childhood obesity. Retention
      from baseline to final collection was 54%. Measures . Self-reported physical
      activity and eating behaviors; measured height and weight were collected at
      baseline and after interventions (average of 20 months). Z-score was compared
      with expected growth without intervention. ANALYSIS: Descriptive statistics,
      chi(2) tests and t-tests, and ANOVA analyses of variance to assess changes in
      health behaviors and weight status. RESULTS: More than 11% of children improved
      their weight status, and 86% of children who began at a healthy weight remained
      there. The average BMI for children who were overweight at enrollment was
      significantly lower after intervention (1.1 kg/m(2) lower for boys and 0.88
      kg/m(2) lower for girls). Overweight and obese children who made improvements in
      key health behaviors showed greater decreases in BMI z-score than those who did
      not improve those behaviors (increased fruit [-.2207 vs. -.0793] and vegetable [
      .2215 vs. -.0855] intake, and drinking less soda [-.1985 vs. -.0912]). There were
      no significant increases in physical activity, and changes in physical activity
      were not related to decreases in BMI z-score in this study. CONCLUSION: Community
      originated interventions to raise awareness about food choices and to change
      policies and environments may improve BMI z-scores.

PMID- 22950921
TI  - The positive influence of state agricultural marketing programs on adults' fruit
      and vegetable consumption.
AB  - PURPOSE: To assess whether state-sponsored agricultural marketing programs had a
      positive influence on adult consumers' fruit and vegetable consumption. DESIGN:
      Differences in fruit and vegetable consumption between 2000 and 2005 in states
      that initiated marketing campaigns during this period and those that did not were
      examined. SUBJECTS: A representative sample (n  =  237,320) of adults aged 18 and
      older from states with and without marketing programs was used. The study used
      data from the 2000 and 2005 Behavioral Risk Factor Surveillance System. MEASURES:
      The number of fruit and vegetable servings per week and the percentage of
      respondents consuming five or more servings of fruits and vegetables per day were
      examined. ANALYSIS: Between-subjects analysis of variance and logistic
      regression. RESULTS: In the absence of a marketing campaign, there was a
      significant decrease in fruit and vegetable consumption between 2000 and 2005. In
      states with campaigns, consumption remained stable or increased. Marketing
      effects were stronger for women than for men. Conclusions . State-sponsored
      agricultural marketing programs had favorable effects on consumers' consumption
      of fruits and vegetables.

PMID- 22950922
TI  - The relationships among socioeconomic status, fruit and vegetable intake, and
      alcohol consumption.
AB  - PURPOSE: We examined the relationships among fruit and vegetable intake, alcohol
      consumption, and socioeconomic status (SES). We hypothesized that fruit and
      vegetable consumption would be inversely associated with alcohol consumption and
      the relationship would differ by SES. DESIGN: A cross-sectional analysis.
      SETTING: Large, urban Midwestern county. SUBJECTS: A unique, racially/ethnically
      diverse sample of 9959 adults (response rate: 66.3%). MEASURES: Fruit and
      vegetable intake was measured using two items that assessed servings per day.
      Alcohol consumption was measured in terms of volume of alcohol consumed and binge
      drinking. Individual measures of SES included education and household income.
      ANALYSIS: Weighted multivariate linear and Poisson regression were used to
      estimate effects. RESULTS: The relationship between fruit and vegetable intake
      and alcohol consumption varied by SES. Those with lower household incomes who
      consumed five or more servings of fruits and vegetables per day were less likely
      to engage in binge drinking relative to those consuming zero to one servings of
      fruits and vegetables per day (risk ratio  =  .66; 95% confidence interval: .46,
      .95). No association was observed for higher-household-income individuals.
      CONCLUSION: We observed an inverse relationship between fruit and vegetable
      consumption and alcohol intake in those with lower household incomes but not in
      those with higher household incomes. Results suggest that the relationship
      between diet and alcohol consumption may be more relevant in populations with
      more restricted economic choices. Results are, however, based on cross-sectional
      data.

PMID- 22950923
TI  - State tobacco control plans: who falls outside the plans?
AB  - PURPOSE: To review published state tobacco control plans (STCPs) to determine the
      extent to which the needs of the states' populations are being addressed. DESIGN:
      A qualitative cross-sectional comparison of states' strategic plans for tobacco
      control as of March 2010. SETTING: Online searches. PARTICIPANTS: The 50 states
      and the District of Columbia. METHOD: Internet-based searches were completed
      using tobacco and other keywords (control, prevention, strategies,
      comprehensive/strategic plan) to obtain all publicly available STCPs; telephone
      follow-up was conducted to ensure that all publicly available plans were
      captured. Each plan was coded by two researchers using a standardized protocol to
      assess provisions made for addressing disparate populations as defined by the
      states. RESULTS: A total of 43 states addressed disparate populations. Thirty-six
      states addressed these populations within published STCPs, six states had
      separate stand-alone tobacco disparities plans, and one addressed it within their
      cancer plan. Specific populations addressed included racial and ethnic
      minorities, blue-collar employees, pregnant women, children under the age of 18,
      and college students. There were also several STCPs that cited the general goal
      of eliminating tobacco use disparities. CONCLUSION: More work is needed to
      address tobacco disparities, including additional planning efforts in some states
      and effective implementation and evaluation among states with plans. States can
      look to the experiences of other states to help guide tobacco control planning
      for their own populations.

PMID- 22950924
TI  - The prevalence of metabolic syndrome and metabolic syndrome risk factors in
      college-aged students.
AB  - PURPOSE: Metabolic syndrome (MetS) is characterized by a constellation of
      metabolic risk factors that consist of the following: atherogenic dyslipidemia,
      elevated blood pressure, elevated glucose associated with insulin resistance,
      prothrombotic state, and proinflammatory state. The objective of the study was to
      quantify the prevalence of MetS among college students and to determine whether
      fatness (body mass index [BMI] and waist circumference) or physical activity was
      more strongly associated with individual components of the MetS. DESIGN: A cross
      sectional study. SETTING: Eau Claire, Wisconsin, United States. SUBJECTS: Authors
      collected health history information and performed assessments of individual MetS
      components for 207 college students aged 18 to 24 years. MEASURES: Physical
      activity levels were self-reported, while direct measurements were obtained for
      MetS components (waist circumference, blood pressure, high-density lipoprotein
      (HDL)-cholesterol, triglycerides, blood glucose). ANALYSIS: Descriptive
      statistics and multiple regression analysis. RESULTS: The prevalence of MetS was
      found to be 6.8% according to the National Cholesterol Education Program Adult
      Treatment Panel III guidelines. The authors also found that 42.5% and 13.0% of
      our sample had one and two MetS components, respectively. Waist circumference was
      independently associated (p < .05) with HDL-cholesterol, triglycerides, and
      systolic blood pressure. CONCLUSION: Our findings provide evidence for the
      presence of MetS on college campuses. It also appears, in part, that central
      adiposity contributes to the high incidence of individual MetS components. Given
      the elevated lifetime risk for cardiovascular disease and lower survival for
      those with risk factors in young adulthood, there appears to be a need for
      primary prevention programs within university and college settings.

PMID- 22950925
TI  - Repeated exposure to media messages encouraging parent-child communication about
      sex: differential trajectories for mothers and fathers.
AB  - PURPOSE: To examine changes in parent-child communication related to sexual
      behavior after exposure to public health messages. DESIGN: Randomized, controlled
      trial that was part of precampaign message testing. SETTING: Exposure occurred
      online or through DVDs mailed to participants and viewed on their personal
      computers. Data collection occurred via a secure Web site. PATIENTS: Participants
      included parents (n  =  1969) living with a child age 10 to 14 years drawn from a
      nationally representative sample of U.S. households. INTERVENTION: Treatment
      participants were exposed to video, audio, and print advertisements that promoted
      the benefits of speaking to their children early and often about delaying
      initiation of sexual activity; messages also directed parents to an informational
      Web site. MEASURES: The dependent variable assessed frequency of parent-child
      communication related to sexual behavior. The primary independent variable was
      treatment assignment. ANALYSIS: Longitudinal growth modeling that included five
      waves of data. RESULTS: The trajectory of growth over time differed between
      fathers in the treatment group and fathers in the control group (F[1, 2357]  = 
      4.15; p < .042), indicating more frequent communication among treatment fathers
      than among control fathers. Trajectories did not differ between mothers in
      treatment and control groups. CONCLUSION: This study demonstrates that father
      child and mother-child communication patterns differ over time in response to
      public health messages. Findings have implication for researchers developing
      health marketing campaigns.

PMID- 22950926
TI  - Evaluating the quality and accessibility of physical activity resources in two
      southern cities.
AB  - PURPOSE: Access and quality of physical activity resources (PARs) influence
      physical activity (PA) participation. This study examined the type, size,
      accessibility, features, amenities, and incivilities of PARs in two cities.
      DESIGN: Researchers identified all PARs within an 800-meter radius of the homes
      of participants from a larger study. Each PAR was evaluated by a trained
      assessor. SETTING: PARs were evaluated in Houston and Austin, Texas. PATIENTS:
      The final sample included 1326 PARs in Houston and 297 in Austin, Texas.
      MEASURES: The 2010 Physical Activity Resource Assessment (PARA), a direct
      observation audit tool, was used to assess the type, size, accessibility,
      features, amenities, and incivilities of a PAR. ANALYSIS: Both t-tests and
      analyses of variance were used to determine differences in features, amenities,
      and incivilities by city, type, and accessibility. RESULTS: Houston PARs had
      greater amenities (t[421]  =  4.445; p < .001) and fewer incivilities (t[371]  = 
      -6.89; p < .001) than Austin PARs. Combination resources had the highest score
      for features (M  =  9.94; standard deviation [SD]  =  5.62); fitness clubs had
      the highest score for amenities (M  =  17.06; SD  =  5.27); and trails had the
      most incivilities (M  =  4.23; SD  =  4.88). Free PARs had greater features (F[3,
      1509]  =  16.87; p < .001), amenities (F[3, 1500]  =  3.13; p  =  .025), and
      incivilities (F[3, 1540]  =  21.97; p < .001) than pay for use PARs. CONCLUSION:
      Improvements to quality and maintenance of existing free PARs may be an
      economical strategy to increase PA.

PMID- 22950927
TI  - A smoker identity measure for experimental, intermittent, and daily college
      student smokers.
AB  - PURPOSE: To provide initial tests of internal consistency reliability and both
      structural and concurrent validity of a smoker identity (SI) scale for college
      student populations. DESIGN: Cross-sectional design. SETTING: Midsouth
      university. PARTICIPANTS: Undergraduates in a random sample of university classes
      completed surveys (92.3% response rate). METHOD: SI items derived from a
      literature review and clinical expertise, lifetime and current tobacco use,
      cigarette purchasing patterns, and quitting variables. ANALYSIS: Current (some
      days or every day) cigarette users (n  =  362) were divided into daily,
      intermittent, and experimental smoker groups. After principal components analysis
      was conducted on the SI items, analysis of variance (ANOVA) was used to assess SI
      differentiation of smoker groups, and correlational analysis or ANOVA was used to
      assess SI relationships with smoking and quitting variables. RESULTS: Eight SI
      items produced a high-internal-consistency, single-factor structure (alpha  = 
      .93) and clearly differentiated the three smoker groups. Higher SI scores
      indicated greater smoking rate, smoking within 30 minutes of awakening, larger
      purchased quantities, and both greater interest and lower confidence in quitting.
      CONCLUSIONS: The scale demonstrated good reliability and validity. Other SI
      measures exist, but this is the first scale to establish utility with
      experimental and intermittent smokers-substantial groups among college students.
      The extent to which cigarette users identify as smokers may provide useful
      information beyond behavioral measures, especially among college students.

PMID- 22950932
TI  - "Eat Healthy, Stay Active!": a coordinated intervention to improve nutrition and
      physical activity among Head Start parents, staff, and children.
AB  - PURPOSE: Examine the effectiveness of the "Eat Healthy, Stay Active!" pilot
      program, a multisite, 6-month educational intervention to promote healthy
      nutrition and physical activity among Head Start staff, parents, and children.
      DESIGN: Comparison of within-group preintervention and postintervention knowledge
      and behavior, along with anthropomorphic measurements. SETTING: The study was
      conducted in a convenience sample of six large Head Start agencies in five
      states. SUBJECTS: Participants included 496 staff, 438 parents, and 112 preschool
      children. INTERVENTION: The 6-month intervention consisted of core trainings and
      reinforcing activities for staff and parents that aligned with children's
      curricula. MEASURES: Pre-post questionnaires and anthropometric measurements
      examined changes in body mass index (BMI), knowledge, and behaviors related to
      nutrition and physical activity. ANALYSIS: Paired t-tests to compare
      preintervention and postintervention weights and BMI; multiple regression
      analyses to examine associations between weight changes and other covariates,
      including knowledge and behavior changes, controlling for sociodemographic
      variables. RESULTS: Each group of participants demonstrated significant
      reductions in BMI (mean  =  30.1 to 29.2; p < .001 in adults and 17.0 to 16.6; p
      < 0.001 in children) and in the proportion of obese children (30% to 21%; p <
      .001) and adults (45% to 40%; p < .001). Child weight changes correlated with
      parent weight changes. CONCLUSION: This intervention showed promising initial
      results, with potential effectiveness as an intervention to promote healthier
      behaviors among adults and children in Head Start settings.

PMID- 22950933
TI  - Identification of environmental, managerial, and sociodemographic correlates of
      hiker volume on the Florida National Scenic Trail.
AB  - PURPOSE: The purpose of this study was to identify the association of
      environmental, managerial, and sociodemographic variables with hiker volume on
      the Florida National Scenic Trail. DESIGN: Monthly hiker count data from 43 count
      stations along the Florida National Scenic Trail were used. For each station the
      characteristics of the built and natural environment as well as sociodemographic
      variables were computed within a Geographic Information System based on census,
      land use, and land cover data, together with managerial data. SETTING: Counts
      were performed on access points of the Florida National Scenic Trail located
      between the panhandle area in the northwest and the Everglades in the south.
      SUBJECTS: A total of 34,734 hikers were counted across the 43 stations over 12
      month periods for years 2003-2004 and 2008-2009. MEASURES: Hiker volume was
      measured through infrared counters and registration cards at trail access points.
      ANALYSIS: A negative binomial regression with monthly hiker counts as response
      variable. RESULTS: Positive associations with hiker volume were observed for
      (population density per hectare) 2 (beta  =  .207, p < .02), residential areas
      (beta  =  .041, p < .0003), household income between $25,000 and $49,999 (beta  =
      .266, p < .0001), household income between $50,000 and $99,999 (beta  =  .135, p
      < .0001), open water (beta  =  .135, p < .0001), and station kilometers north
      (beta  =  .003, p < .0001). Negative associations with hiker volume were observed
      for age <18 (beta  =  -.305, p < .0001) and presence of trail fees (beta  =  
      .583, p < .0001). Positive and negative associations were observed for different
      categories in categorical variables including prominent vegetation type (p <
      .0001), trail management agency (p < .0001), and month (p < .0001). CONCLUSIONS:
      The correlates should be considered for the design, planning, and promotion of
      hiking trails in publicly managed areas to increase hiker volume.

PMID- 22950936
TI  - We are beginning to speak with one voice: consensus statement on wellness
      incentives.

PMID- 22950937
TI  - The high bar of return on investment in wellness.

PMID- 22950938
TI  - Aboriginal and Torres Strait Islander utilisation of the Quitline service for
      smoking cessation in South Australia.
AB  - Smoking prevalence among Indigenous Australians far exceeds that of non
      Indigenous Australians and is considered the greatest contributor to burden of
      disease for Indigenous Australians. The Quitline is a primary intervention for
      facilitating smoking cessation and, given the health implications of tobacco use,
      maximising its effectiveness for Indigenous Australians is imperative. However,
      the utilisation and effectiveness of this service within the Indigenous
      Australian population has not been examined. This study explores the utilisation
      of the South Australian Quitline by smokers identifying as Indigenous Australian.
      Quitline counsellors collected data regarding demographic characteristics, and
      smoking and quitting behaviour from Quitline callers in 2010. Results indicated
      that the proportion of Indigenous and non-Indigenous smokers who registered for
      the service was comparable. Demographic variables and smoking addiction at time
      of registration with the Quitline were similar for Indigenous and non-Indigenous
      callers. However, results indicated that Indigenous callers received
      significantly fewer callbacks than non-Indigenous callers and were significantly
      less likely to set a quit date. Significantly fewer Indigenous callers reported
      that they were still successfully quit at 3 months. Thus, Indigenous Australian
      callers may be less engaged with the Quitline and further research is required
      exploring whether the service could be tailored to make it more engaging for
      Indigenous Australians who smoke. 

PMID- 22950939
TI  - CARTs to the rescue: therapeutic potential of chimeric antigen receptor T-cells
      in patients with B-cell malignancies.

PMID- 22950940
TI  - Involvement of microRNA-335-5p in cytoskeleton dynamics in mouse oocytes.
AB  - MicroRNA is a short RNA molecule expressed in eukaryotic cells that is involved
      in multiple processes, including translational repression, target degradation and
      gene silencing. However, its specific role(s) in these processes remains largely
      unknown, especially in terms of germ cell development. The present study
      identified a microRNA, namely miR-335-5p, that is involved in mouse oocyte
      meiosis. MiR-335-5p was highly expressed in oocytes, but levels decreased
      markedly shortly after fertilisation. Microinjection of miR-335-5p or its
      inhibitor into oocytes resulted in a higher proportion of 2-cell-like MII oocytes
      and oocytes at the germinal vesicle breakdown and/or MI stage, indicating failure
      of asymmetric oocyte division. This may be due to regulation of actin because
      perturbation of miR-335-5p resulted in reduced expression of actin nucleator
      Daam1, a member of the Formin family. Moreover, injection of miR-335-5p or its
      inhibitor resulted in aberrant spindle morphology, namely an elongated spindle
      and multiple poles spindle. After injection of oocytes, levels of phosphorylated
      extracellular signal-regulated kinase 1/2 (ERK1/2) decreased, suggesting that miR
      335-5p may regulate spindle formation via the mitogen-activated protein kinase
      pathway. Overexpression and inhibition of miR-335-5p had no effect on embryo
      development. Together, the results of the present study indicate that miR-335-5p
      is a novel regulator expressed in oocytes that is involved in cytoskeleton
      dynamics.

PMID- 22950941
TI  - Characteristics of an educational publication sourced from deaths investigated by
      the coroner that is reported to have promoted practice change.
AB  - OBJECTIVE: The purpose of this study was to investigate the characteristics of
      the Residential Aged Care Coronial Communique that have promoted previously
      reported professional practice change, and to explore the circumstances of these
      changes. METHODS: This was an exploratory, qualitative study for which data was
      collected through semi-structured interview of 15 subscribers to the Residential
      Aged Care Coronial Communique. RESULTS: The Residential Aged Care Coronial
      Communique was reported to promote self-reported practice change though the
      inclusion of case studies, by being associated with the Coroner, and by providing
      evidence to justify change. The combination of existing concerns about risk and
      staff awareness, in conjunction with reading the Residential Aged Care Coronial
      Communique was also reported to promote practice change, as was having the
      support of senior staff and the authority to implement change. CONCLUSIONS: The
      combination of narrative case studies in the context of an educational
      publication associated with the Coroner's Office has been reported to provided
      evidence and incentive to promote professional practice change in an aged care
      setting. However the relative influence of the Residential Aged Care Coronial
      Communique, and other background circumstance and facilitating factors on
      practice change cannot be determined from this study.

PMID- 22950942
TI  - Water safety education among primary school children in Grenada.
AB  - Drowning is a common cause of death among children. Successful prevention
      interventions currently used in developed countries are often not transferable
      into developing countries due to differences in both environment and resources.
      In this study, we adapted a water safety education programme developed by the
      American Red Cross for primary school students in Grenada. Water safety knowledge
      before and after the training session was assessed using a nine-question
      evaluation tool. Following the training, a survey was administered to all
      teachers to assess the adaptability and effectiveness of the WHALE Tales
      training. Fifty-six students (30% males) completed the training. The age range
      was between 5 and 12 years old. Participants' water safety knowledge increased
      15% (p < 0.01). Mean scores of correct answers increased for every grade level,
      ranging from a 5% increase for first graders to 33% increase for second graders.
      The findings from this study suggested that implementation of such a programme is
      effective. With cultural modifications and outsourcing, we believe this adapted
      programme would be successful in Grenada and other similar settings. 

PMID- 22950943
TI  - Searching for global descriptors of engineered nanomaterial fate and transport in
      the environment.
AB  - Engineered nanomaterials (ENMs) are a new class of environmental pollutants.
      Researchers are beginning to debate whether new modeling paradigms and
      experimental tests to obtain model parameters are required for ENMs or if
      approaches for existing pollutants are robust enough to predict ENM distribution
      between environmental compartments. This Account outlines how experimental
      research can yield quantitative data for use in ENM fate and exposure models. We
      first review experimental testing approaches that are employed with ENMs. Then we
      compare and contrast ENMs against other pollutants. Finally, we summarize the
      findings and identify research needs that may yield global descriptors for ENMs
      that are suitable for use in fate and transport modeling. Over the past decade,
      researchers have made significant progress in understanding factors that
      influence the fate and transport of ENMs. In some cases, researchers have
      developed approaches toward global descriptor models (experimental, conceptual,
      and quantitative). We suggest the following global descriptors for ENMs: octanol
      water partition coefficients, solid-water partition coefficients, attachment
      coefficients, and rate constants describing reactions such as dissolution,
      sedimentation, and degradation. ENMs appear to accumulate at the octanol-water
      interface and readily interact with other interfaces, such as lipid-water
      interfaces. Batch experiments to investigate factors that influence retention of
      ENMs on solid phases are very promising. However, ENMs probably do not behave in
      the same way as dissolved chemicals, and therefore, researchers need to use
      measurement techniques and concepts more commonly associated with colloids.
      Despite several years of research with ENMs in column studies, available
      summaries tend to discuss the effects of ionic strength, pH, organic matter, ENM
      type, packing media, or other parameters qualitatively rather than reporting
      quantitative values, such as attachment efficiencies, that would facilitate
      comparison across studies. Only a few structure-activity relationships have been
      developed for ENMs so far, but such evaluations will facilitate the understanding
      of the reactivities of different forms of a single ENM. The establishment of
      predictive capabilities for ENMs in the environment would enable accurate
      exposure assessments that would assist in ENM risk management. Such information
      is also critical for understanding the ultimate disposition of ENMs and may
      provide a framework for improved engineering of nanomaterials that are more
      environmentally benign. 

PMID- 22950946
TI  - Adolescents and alcohol: an explorative audience segmentation analysis.
AB  - BACKGROUND: So far, audience segmentation of adolescents with respect to alcohol
      has been carried out mainly on the basis of socio-demographic characteristics. In
      this study we examined whether it is possible to segment adolescents according to
      their values and attitudes towards alcohol to use as guidance for prevention
      programmes. METHODS: A random sample of 7,000 adolescents aged 12 to 18 was drawn
      from the Municipal Basic Administration (MBA) of 29 Local Authorities in the
      province North-Brabant in the Netherlands. By means of an online questionnaire
      data were gathered on values and attitudes towards alcohol, alcohol consumption
      and socio-demographic characteristics. RESULTS: We were able to distinguish a
      total of five segments on the basis of five attitude factors. Moreover, the five
      segments also differed in drinking behavior independently of socio-demographic
      variables. CONCLUSIONS: Our investigation was a first step in the search for
      possibilities of segmenting by factors other than socio-demographic
      characteristics. Further research is necessary in order to understand these
      results for alcohol prevention policy in concrete terms.

PMID- 22950947
TI  - Ratiometric and selective fluorescent sensor for Zn2+ as an "off-on-off" switch
      and logic gate.
AB  - A new chemosensor, 2,3,15,16-tetrakis(pyridin-2-yl)-7,8,10,11,20,21,23,24
      octahydro[1,4,7,10,13,16]hexaoxacyclooctadecino[2,3-g:11,12-g']diquinoxaline (1),
      containing 2,3-bis(pyridin-2-yl)quinoxaline and crown ether moieties, has been
      designed and found to be a ratiometric and selective fluorescent detector of
      Zn(2+) over a wide range of tested metal ions. The addition of Zn(2+) to the
      solution of 1 in acetonitrile induced the formation of a 1:2 ligand-metal
      complex, 1-Zn(2+), which exhibits a remarkable enhanced fluorescent emission
      centered at 460 nm, with the disappearance of the fluorescent emission of 1
      centered at 396 nm due to the mechanism of internal charge transfer. In contrast,
      the presence of K(+) results in the fluorescence quenching of 1 and 1-Zn(2+)
      through the photoinduced electron-transfer mechanism. These results demonstrate
      that 1 can perform as not only an INHIBIT logic gate but also an "off-on-off"
      molecular switch triggered by Zn(2+) and K(+). The structure of complex 1-Zn(2+)
      has been characterized by single-crystal X-ray crystallography, mass
      spectrometry, and (1)H NMR titration experiments. Density functional theory
      calculation results on 1 and the 1-Zn(2+) complex are well consistent with the
      experimental results.

PMID- 22950945
TI  - Classification of human genomic regions based on experimentally determined
      binding sites of more than 100 transcription-related factors.
AB  - BACKGROUND: Transcription factors function by binding different classes of
      regulatory elements. The Encyclopedia of DNA Elements (ENCODE) project has
      recently produced binding data for more than 100 transcription factors from about
      500 ChIP-seq experiments in multiple cell types. While this large amount of data
      creates a valuable resource, it is nonetheless overwhelmingly complex and
      simultaneously incomplete since it covers only a small fraction of all human
      transcription factors. RESULTS: As part of the consortium effort in providing a
      concise abstraction of the data for facilitating various types of downstream
      analyses, we constructed statistical models that capture the genomic features of
      three paired types of regions by machine-learning methods: firstly, regions with
      active or inactive binding; secondly, those with extremely high or low degrees of
      co-binding, termed HOT and LOT regions; and finally, regulatory modules proximal
      or distal to genes. From the distal regulatory modules, we developed
      computational pipelines to identify potential enhancers, many of which were
      validated experimentally. We further associated the predicted enhancers with
      potential target transcripts and the transcription factors involved. For HOT
      regions, we found a significant fraction of transcription factor binding without
      clear sequence motifs and showed that this observation could be related to strong
      DNA accessibility of these regions. CONCLUSIONS: Overall, the three pairs of
      regions exhibit intricate differences in chromosomal locations, chromatin
      features, factors that bind them, and cell-type specificity. Our machine learning
      approach enables us to identify features potentially general to all transcription
      factors, including those not included in the data.

PMID- 22950948
TI  - Magnetoporation and magnetolysis of cancer cells via carbon nanotubes induced by
      rotating magnetic fields.
AB  - Weak magnetic fields (40 and 75 mT) were used either to enhance cell membrane
      poration (magnetoporation) or to ablate cultured human tumor cells (magnetolysis)
      by polymer-coated multiwalled carbon nanotubes, which form rotating bundles on
      exposure to magnetic fields. Findings of this study have potential clinical
      applications including enhanced tumor cell poration for targeted cancer
      chemotherapy and mechanical ablation of tumors.

PMID- 22950949
TI  - Chlamydia prevention indicators for Australia: review of the evidence from New
      South Wales.
AB  - BACKGROUND: Annual notifications of chlamydia (Chlamydia trachomatis) diagnoses
      have increased steadily in Australia in the last decade. To guide public health
      programs, we developed 10 national chlamydia prevention indicators and report on
      each indicator for New South Wales (NSW). METHODS: Using systematic methods, we
      reviewed the literature to report on the 10 health and behaviour indicators for
      15- to 29-year-old heterosexuals in NSW from 2000. We included data with two or
      more time points. RESULTS: Chlamydia notification rates (Indicator 1) in 15- to
      29-year-olds have increased by 299%, from 237 per 100000 population in 2001 to
      946 per 100000 population in 2010; and the percent of 15- to 34-year-olds with an
      annual Medicare-rebated chlamydia test (Indicator 2) increased by 326%, from 1.9%
      in 2001 to 8.1% in 2010. Since 2004, sentinel surveillance showed a 28% increase
      in chlamydia prevalence (Indicator 3) in 15- to 29-year-old females tested at
      their first sexual health service visit (from 8.5% in 2004 to 10.9% in 2010) but
      no significant increase in males. No NSW-specific chlamydia incidence (Indicator
      4) was available. Pelvic inflammatory disease hospitalisation separations rate
      decreased from 0.58 per 1000 in 2001 to 0.44 per 1000 in 2010 in 15- to 29-year
      old females (Indicator 5).Secondary school surveys in 2002 and 2008 showed
      chlamydia knowledge increased in males. The sexual risk-taking behaviour of young
      people remained unchanged (Indicators 6-10). CONCLUSIONS: Although notifications
      have risen steeply, the modest increase in chlamydia prevalence maybe a more
      realistic reflection of transmission rates. Strategies are needed to increase
      testing and to modify sexual risk behaviour. Crucial gaps in epidemiological data
      were identified.

PMID- 22950950
TI  - A taxonomy of primary health care practices: an avenue for informing management
      and policy implementation.
AB  - Health policy and practice managers often treat primary practices as being
      homogenous, despite evidence that these organisations vary along multiple
      dimensions. This treatment can be a barrier to the development of a strong health
      care system. Therefore, a more sophisticated taxonomy of organisations could
      inform management and policy to better cater to the diversity of practice
      contexts, needs and capabilities. The purpose of this study was to categorise
      primary practices using practice features and characteristics associated with the
      job satisfaction of GPs. The current study uses data from 3906 GPs from the 2008
      wave of the MABEL survey. Seven configurations of primary health care practices
      emerged from multivariate cluster analyses. The configurations incorporate, yet
      move beyond, simplistic categorisations such as geographic location and highlight
      the complexity facing managers and health policy interventions. The
      multidimensional configurations in the taxonomy are a mechanism for informing
      health care management and policy. The process of deriving configurations can be
      applied in a variety of countries and contexts. 

PMID- 22950951
TI  - Microarray analysis of mRNA from cumulus cells following in vivo or in vitro
      maturation of mouse cumulus-oocyte complexes.
AB  - The IVM of mammalian cumulus-oocyte complexes (COCs) yields reduced oocyte
      developmental competence compared with oocytes matured in vivo. Altered cumulus
      cell function during IVM is implicated as one cause for this difference. We have
      conducted a microarray analysis of cumulus cell mRNA following IVM or in vivo
      maturation (IVV). Mouse COCs were sourced from ovaries of 21-day-old CBAB6F1 mice
      46h after equine chorionic gonadotrophin (5IU, i.p.) or from oviducts following
      treatment with 5IU eCG (61h) and 5IU human chorionic gonadotrophin (13h). IVM was
      performed in alpha-Minimal Essential Medium with 50 mIU FSH for 17h. Three
      independent RNA samples were assessed using the Affymetrix Gene Chip Mouse Genome
      430 2.0 array (Affymetrix, Santa Clara, CA, USA). In total, 1593 genes were
      differentially expressed, with 811 genes upregulated and 782 genes downregulated
      in IVM compared with IVV cumulus cells; selected genes were validated by real
      time reverse transcription-polymerase chain reaction (RT-PCR). Surprisingly,
      haemoglobin alpha (Hba-a1) was highly expressed in IVV relative to IVM cumulus
      cells, which was verified by both RT-PCR and western blot analysis. Because
      haemoglobin regulates O2 and/or nitric oxide availability, we postulate that it
      may contribute to regulation of these gases during the ovulatory period in vivo.
      These data will provide a useful resource to determine differences in cumulus
      cell function that are possibly linked to oocyte competence.

PMID- 22950952
TI  - Perceptions of barriers to discussing and testing for sexually transmitted
      infections in a convenience sample of general practice patients.
AB  - We aimed to identify patient perceptions of barriers to discussing sexually
      transmitted infections (STIs) at the primary care level. An anonymous
      questionnaire was available to patients (16-70 years) in the waiting room of four
      metropolitan Perth general practices. Results are based on 370 participant views
      (9.5% of the potential target population). Patients felt comfortable discussing
      STIs with their general practitioner (GP) and their level of comfort would be
      enhanced if they knew their GP had a special interest or qualification in sexual
      health. Willingness to discuss issues increased or remained unchanged if the GP
      took time to explain it to them or was a good listener. Patients were willing to
      discuss STIs if they were a new patient and irrespective of the GP's gender and
      age. Fewer patients were willing to discuss STIs if they knew the GP socially.
      Patients who had sex with a new partner were willing to request a STI test from
      their GP. Patients were not embarrassed if discussion was initiated in a
      consultation unrelated to sexual health and did not mind discussing the topic in
      the presence of a partner or parent, though this depended on circumstances.
      Waiting room STI test advertising did not affect patient comfort level. Patients
      would involve their GP when seeking information about STIs. Patients have fewer
      barriers to discussing sexual health matters than perceived by GPs. 

PMID- 22950953
TI  - Studies on the structure of N-phenyl-substituted hexaaza[1(6)]paracyclophane:
      synthesis, electrochemical properties, and theoretical calculation.
AB  - The N-phenyl-substituted hexaaza[1(6)]paracyclophane (3, hexamer) has been
      synthesized successfully in two steps and the noncoplanar conformation was
      calculated by gaussian program. The electrochemical properties exhibited lots of
      interesting results and each overlapping oxidative wave contained two-electron
      transfer.

PMID- 22950954
TI  - Obesity. Struggle the global epidemic.

PMID- 22950955
TI  - Drug treatment of metabolic syndrome.
AB  - The metabolic syndrome is a constellation of risk factors for cardiovascular
      diseases including: abdominal obesity, a decreased ability to metabolize glucose
      (increased blood glucose levels and/or presence of insulin resistance),
      dyslipidemia, and hypertension. Patients who have developed this syndrome have
      been shown to be at an increased risk of developing cardiovascular disease and/or
      type 2 diabetes. Genetic factors and the environment both are important in the
      development of the metabolic syndrome, influencing all single components of this
      syndrome. The goals of therapy are to treat the underlying cause of the syndrome,
      to reduce morbidity, and to prevent complications, including premature death.
      Lifestyle modification is the preferred first-step treatment of the metabolic
      syndrome. There is no single effective drug treatment affecting all components of
      the syndrome equally known yet. However, each component of metabolic syndrome has
      independent goals to be achieved, so miscellaneous types of drugs are used in the
      treatment of this syndrome, including weight losing drugs, antidiabetics,
      antihypertensives, antilipemic and anticlothing drugs etc. This article provides
      a brief insight into contemporary drug treatment of components the metabolic
      syndrome. 

PMID- 22950956
TI  - Challenging the evidence based medicine principles among clinical obesity
      treatments.
AB  - Obesity is among the greatest health problems worldwide. However, there is a
      certain lack in regard to objective evidence-based clinical therapeutic
      algorithms. The conservative therapy (lifestyle changes, pharmacotherapy) often
      fails to attain clinically significant weight lost. For this reason, more
      effective forms of treatment were developed (for example bariatric surgery or
      newly emerging field of endoscopic gastroenterological devices). The
      implementation of surgical therapy is marked with relatively narrowly stated
      indication parameters. The endoscopic methods showed promising results in weight
      loss, within satisfying safety profiles, although there are no clear defined
      positions of endoscopic devices in the treatment of obesity. Endoscopic treatment
      seems to be especially interesting as an alternative to surgery, because of
      significant surgical risk reduction. This review presents an analysis of the
      position of invasive treatments of obesity.

PMID- 22950957
TI  - Obesity in the cardiovascular continuum.
AB  - A higher prevalence of coronary heart disease, cardiac and overall mortality is
      associated with obesity. The development of obesity appears in different
      adaptations in the morphology of cardiac structure and function. Obesity causes
      eccentric hypertrophy and changes in diastolic function of left ventricle. A
      systolic on diastolic heart dysfunction results from the breakdown of
      compensatory pace to raised wall stress and dilatation of chambers. Obesity does
      not possess primary cause and effect relationship with cardiovascular disease,
      such as LDL cholesterol. It is regarded as a means of facilitating factors such
      as hypertension, diabetes or cigarette smoking. Adipose tissue in this manner
      works as the hormone generating tissue, secreting various peptides and secondary
      messengers and inflammatory cytokines. Pharmacotherapy can be a useful component
      in the global fight against obesity. Besides repeating re-evaluations of weight
      loosing drug treatment with respect to efficiency or safety for continuous use,
      one must not underappreciate the pretreatment risk-assessments and expected
      benefits of treatment, along with impact on the patient's quality of life and
      motivation. Pharmacotherapy of obesity is reserved for obese people with body
      mass index (BMI) >= 30 kg/m2 but also in individuals with BMI 27 .0 and 29 .9
      kg/m2 and obesity related comorbidities as obstructive sleep apnea, hypertension,
      dyslipidemias, diabetes and metabolic syndrome. Although connections between
      obesity and cardiovascular diseases (CVD) are acknowledged for over dozen of
      years, there is still a lack of scientific research into the field and it is a
      challenge for future studies.

PMID- 22950958
TI  - The position of endoscopic procedures in the treatment of obesity.
AB  - Obesity is a worldwide health problem associated with substantial morbidity and
      cost. Lifestyle modification and pharmacotherapy for obesity have limited
      benefit. Bariatric surgery is effective but with substantial risks, considerable
      cost and limited patient applicability. Endoscopic approach to obesity has
      evolved as a result of an attempt to replicate some of the anatomical
      manipulations and the physiological effects of the traditional weight loss
      surgery in a minimally invasive manner. Endoscopic interventions performed
      entirely through the GI tract offer the potential for an ambulatory weight loss
      procedure that is more cost-effective compared with current surgical approaches.
      There are two main endoscopic weight loss modalities - restrictive and
      malabsorptive. Restrictive procedures act to decrease gastric volume by space
      occupying prosthesis and/or by suturing or stapling devices that alter gastric
      anatomy while malabsorptive procedures tend to create malabsorption by preventing
      food contact with the duodenum and proximal jejunum. Restrictive endoscopic
      procedures include intragastric balloon treatment, endoluminal vertical
      gastroplasty, transoral gastroplasty (TOGA) and transoral endoscopic restrictive
      implant system (TERIS). The duodenojejunal bypass sleeve (DJBS) is a
      malabsorptive device that mimics such surgical procedure. Gastroduodenojejunal
      bypass sleeve is a combination of both procedures. Except for intragastric
      balloon all mentioned procedures are rather novel, tested on a small number of
      subjects and with limited knowledge on safety and long-term efficacy. Owing to
      evolving field of evidence-based medicine with demand for rigorous evaluation of
      the scientific evidence these therapies need to be carefully tested in a
      randomized controlled manner to determine their safety and efficacy in the short
      and long-term. This review is aimed to compare endoscopic bariatric interventions
      with each other and with other weight loss modalities including conventional
      treatment and surgical procedures. 

PMID- 22950959
TI  - Endocrinology and immunology of obesity, obesity vaccines.
AB  - The amount of body fat is precisely regulated in the overall process of energy
      homeostasis. Multiple organ systems participate in the regulatory process. Key
      regulatory signals reach the brain from the blood and control food intake and
      energy expenditure. The hypothalamus region integrates neurohormonal signaling
      from gut and adipose tissue. Morbid obesity is also associated with low grade
      systemic inflammation and immune activation. It can be at least in part regarded
      as an inflammatory disease. The anti-ghrelin vaccine decreases food intake,
      decreases hypothalamic orexigenic signals and increases energy expenditure and
      therefore might become an alternative treatment tool. 

PMID- 22950960
TI  - Multifaceted individualities in pharmacological treatments of obesity.
AB  - Simply put, there is no cure for obesity. Pharmaceuticals that induce weight loss
      of extent of at least 5% from baseline are applied and tested as the weight
      loosing drugs. Available guidelines include recommendations that pharmacologic
      treatment of obesity may be offered to patients with BMI > 30 kg/m2; or BMI >27
      kg/m2 and obesity related comorbidity. Both categories cumulatively include
      essential boundary condition of failing to achieve clinically significant weight
      loss through diet and exercise alone. In despite the exceedingly growing number
      of investigations and approaches, overall achievements in pharmacological
      treatments of obesity are limited. Antiobesity drugs are typically burdened with
      issues concerning the sustainability of lost weight, besides limitations in short
      term efficiency. Another important problem lays in the fact that the drug induced
      weight loss could be annihilated or reversed if patient does not adhere to
      personal lifestyle changes. Later include adjustments in behaviour sphere,
      dietary habits and physical activity. Recently, focus of clinical interests came
      to prevention of obesity epidemic through optimization of chronic
      pharmacotherapies, especially ones associated with weight gain side-effect. This
      review presents the most important representatives of antiobesity drugs and
      essential principles that ought to be taken in to count in order to treat obesity
      more successfully.

PMID- 22950961
TI  - Using information and communication technologies to consult with patients in
      Victorian primary care: the views of general practitioners.
AB  - Information and communication technologies such as email, text messaging and
      video messaging are commonly used by the general population. However,
      international research has shown that they are not used routinely by GPs to
      communicate or consult with patients. Investigating Victorian GPs' perceptions of
      doing so is timely given Australia's new National Broadband Network, which may
      facilitate web-based modes of doctor-patient interaction. This study therefore
      aimed to explore Victorian GPs' experiences of, and attitudes toward, using
      information and communication technologies to consult with patients. Qualitative
      telephone interviews were carried out with a maximum variation sample of 36GPs
      from across Victoria. GPs reported a range of perspectives on using new
      consultation technologies within their practice. Common concerns included medico
      legal and remuneration issues and perceived patient information technology
      literacy. Policy makers should incorporate GPs' perspectives into primary care
      service delivery planning to promote the effective use of information and
      communication technologies in improving accessibility and quality of general
      practice care. 

PMID- 22950962
TI  - Mollusk glue inspired mucoadhesives for biomedical applications.
AB  - Chitosan (CH), partially N-deacetylated chitin, is a biodegradable and
      biocompatible polymer that has shown great potential in drug delivery and tissue
      engineering applications. Although bioadhesive, CH has limited mucoadhesion in
      wet conditions due to weak interactions with biological surfaces. DOPA (3,4
      dihydroxy-L-phenylalanine), a catechol-containing molecule naturally present in
      marine mussel foot proteins, has been shown to increase the mucoadhesion of
      several polymers. We report here a simple and bioinspired approach to enhance CH
      mucoadhesion in wet conditions by preparing mixed hydrogels including CH and
      different catechol-containing compounds, namely DOPA, hydrocaffeic acid (HCA),
      and dopamine (DA). We characterized the hydrogels for their swelling, release
      kinetics of the catechol compounds, and mucoadhesive strength to rabbit small
      intestine. The swelling of the hydrogels was pH dependent with maximum swelling
      at pH 1. The hydrogel swelling was higher in the presence of the DOPA and DA but
      lower in the presence of HCA. HCA/CH hydrogel also showed the slowest catechol
      release, most likely due to electrostatic interactions between CH and HCA. Lower
      hydrogel swelling and slower HCA release resulted in increased mucoadhesion:
      HCA/CH showed more than 2-fold enhancement of mucoadhesion to rabbit small
      intestine compared to CH alone. Since it is known that catechol compounds can be
      oxidized, we analyzed the oxidation of DOPA, HCA, and DA at different pH values
      and its effect on mucoadhesion. We found that oxidation occurring before contact
      with the intestinal mucosa did not improve mucoadhesion, while oxidation
      occurring during the contact further increased the mucoadhesion of HCA/CH
      hydrogels. These results show that mucoadhesion of CH hydrogels can be increased
      with a simple bioinspired approach, which has the potential to be applied to
      other polymers since it does not require any chemical modification.

PMID- 22950963
TI  - The role of hypoxia-induced genes in ovarian angiogenesis.
AB  - The hypoxic microenvironment that occurs in fast-growing tissue such as the
      corpus luteum (CL) is a major contributor to its ability to survive via the
      induction of an intricate vascular network. Cellular responses to hypoxia are
      mediated by hypoxia-inducible factor-1 (HIF-1), an oxygen-regulated
      transcriptional activator. HIF-1, a heterodimer consisting of a constitutively
      expressed beta subunit and an oxygen-regulated alpha subunit, binds to the
      hypoxia responsive element (HRE) present in the promoter regions of responsive
      genes. This review summarises evidence for the involvement of hypoxia and HIF
      1alpha in CL development and function. Special emphasis is given to hypoxia
      induced, luteal cell-specific expression of multiple genes (vascular endothelial
      growth factor A (VEGFA), fibroblast growth factor 2 (FGF-2), prokineticin
      receptor 2 (PK-R2), stanniocalcin 1 (STC-1) and endothelin 2 (EDN-2) that
      participate in the angiogenic process during CL formation.

PMID- 22950964
TI  - Dynamics and binding affinity of spin-labeled stearic acids in beta
      lactoglobulin: evidences from EPR spectroscopy and molecular dynamics simulation.
AB  - beta-Lactoglobulin (beta-LG) is a member of the lipocalin protein family involved
      in the transport of fatty acids and other small hydrophobic molecules. The main
      binding site is at a central cavity, referred to as "calyx", formed by the
      protein beta-barrel sandwich. Continuous-wave and pulsed Fourier transform
      electron spin resonance (cw- and FT-EPR) spectroscopy and molecular dynamics (MD)
      simulation were combined to investigate the interaction of fatty acids with
      bovine beta-LG. Stearic acid bearing the nitroxide label at different positions,
      n, along the acyl chain (n-SASL, n = 5, 7, 10, 12, 16) were used. The EPR data
      show that the protein affinity for SASL decreases on going from n = 5 to 16. This
      behavior is due to the accommodation of the SASL in the protein calyx, which is
      hampered by steric hindrance of the doxyl ring for n >= 10, as evidenced by MD
      data. Conformation and dynamics of 5-SASL are similar to those of the unlabeled
      stearate molecule. 5-SASL in the protein binding site undergoes librational
      motion of small amplitude on the nanosecond time scale at cryogenic temperature
      and rotational dynamics with correlation time of 4.2 ns at physiological
      temperature. The results highlight the dynamical features of fatty acids/beta-LG
      interaction.

PMID- 22950965
TI  - An audit of pneumococcal and hepatitis vaccination in an outpatient HIV clinic.
AB  - BACKGROUND: HIV-positive adults are at risk of vaccine preventable infections
      including Streptococcus pneumoniae, hepatitis A virus (HAV) and hepatitis B virus
      (HBV). Uptake of immunisations in HIV patients is suboptimal despite evidence of
      efficacy. METHODS: An audit was made of the vaccination records in 200 adult HIV
      positive regular clinic attendees, with a CD4+ count >200 cells MUL(-1). RESULTS:
      Medical records or laboratory data revealed that 10% had been vaccinated against
      S. pneumoniae; 74% were immune or immunised against HAV; 40% had evidence of
      natural infection with HBV and 84% of nonimmune patients had been vaccinated.
      CONCLUSIONS: Strategies to improve vaccine uptake are required.

PMID- 22950966
TI  - Would the real Waldenstrom cell line please stand up?

PMID- 22950967
TI  - Demystifying cultural sensitivity and equity of care.
AB  - While most health professionals would like to believe that the care they provide
      is culturally sensitive, a poor understanding of the concepts of cultural
      sensitivity and equity of care often results in the contrary. In order to ensure
      equity of care for all its clients, it becomes necessary for health services to
      provide care that is culturally sensitive. This letter attempts to explain these
      concepts with the help of two everyday examples.

PMID- 22950969
TI  - 'You're more likely to tell the GP if you're asked': women's views of care from
      general practitioners in the first postpartum year.
AB  - New mothers and their infants are high frequency users of primary health care
      services in Australia providing opportunities for GPs to engage with women about
      common postnatal morbidities. This study aimed to explore women's views of GP
      care in the first year following birth. We used semistructured interviews with a
      subsample of women who had participated in a population-based survey of women who
      gave birth in two Australian states (Victoria and South Australia) in 2007.
      Twenty-nine women were interviewed. Prominent themes that emerged were around
      issues of disclosure, including women's views on ways practitioner interactions
      and systems of care facilitate or hinder disclosure and subsequent discussion of
      health problems. Women reflected on the role GPs played in their health and
      wellbeing after childbirth, the importance of enquiry, communication style and
      the way access to, and time in, consultations impact on disclosure, perceived
      support and discussions. To improve care for women after childbirth we need to
      know the contexts that facilitate disclosure. Findings from this qualitative
      study deliver an important message to clinicians: women value primary care,
      identify issues that facilitate and hinder disclosure and describe 'good'
      encounters as ones where they feel understood, supported and reassured.

PMID- 22950968
TI  - Analysis of variation at transcription factor binding sites in Drosophila and
      humans.
AB  - BACKGROUND: Advances in sequencing technology have boosted population genomics
      and made it possible to map the positions of transcription factor binding sites
      (TFBSs) with high precision. Here we investigate TFBS variability by combining
      transcription factor binding maps generated by ENCODE, modENCODE, our previously
      published data and other sources with genomic variation data for human
      individuals and Drosophila isogenic lines. RESULTS: We introduce a metric of TFBS
      variability that takes into account changes in motif match associated with
      mutation and makes it possible to investigate TFBS functional constraints
      instance-by-instance as well as in sets that share common biological properties.
      We also take advantage of the emerging per-individual transcription factor
      binding data to show evidence that TFBS mutations, particularly at evolutionarily
      conserved sites, can be efficiently buffered to ensure coherent levels of
      transcription factor binding. CONCLUSIONS: Our analyses provide insights into the
      relationship between individual and interspecies variation and show evidence for
      the functional buffering of TFBS mutations in both humans and flies. In a broad
      perspective, these results demonstrate the potential of combining functional
      genomics and population genetics approaches for understanding gene regulation.

PMID- 22950970
TI  - Genetics and diabetic retinopathy.
AB  - There are many reasons to suspect a genetic influence on the development and
      progression of diabetic retinopathy, including substantial variability in disease
      severity among patients with similar risk factors. Linkage studies have suggested
      associations with chromosomes 1, 3, 12 and others. The most studied individual
      genes are those encoding vascular endothelial growth factor, aldose reductase,
      and the receptor for advanced glycation end products, all of which have shown
      statistically significant associations in multiple series from various parts of
      the world. At this time, no definite genetic associations with diabetic
      retinopathy have been consistently reported. This may be due to small sample
      sizes, differences in study design, underlying genetic differences between study
      populations, or other factors. As we continue to collect data, these
      relationships may become more clear.

PMID- 22950972
TI  - Slow magnetic relaxations in manganese(III) tetra(meta-fluorophenyl)porphyrin
      tetracyanoethenide. Comparison with the relative single chain magnet ortho
      compound.
AB  - Mn(III) tetra(meta-fluorophenyl)porphyrin-tetracyanoethenide coordination polymer
      (abbreviated meta-F) was synthesized and crystallographically and magnetically
      characterized. The compound crystallizes in the space group C2/c with four
      equivalent molecules in the unit cell arranged along two symmetry related
      nonparallel linear chain directions. Magnetic properties were studied by SQUID dc
      magnetization and ac susceptibility techniques and high field-high frequency
      electron spin resonance (HF-ESR). Glassy transition to a ferromagnetic-like state
      is observed at 10 K accompanied by slow magnetic relaxations. The glassiness is
      interpreted as due to 3D domain wall pinning. In a bias dc magnetic field the
      width of the relaxation time distribution decreases and the relaxations become
      similar to the relaxations of the single chain magnet Mn(III) tetra(ortho
      fluorophenyl)porphyrin-tetracyanoethenide (abbreviated ortho-F), for which
      comparative HF-ESR studies were also conducted in this work. Magnetic properties
      of these two compounds are compared, and the nature of magnetic relaxations in
      meta-F is discussed.

PMID- 22950973
TI  - 'Talk to us like we're people, not an X-ray': the experience of receiving care
      for chronic pain.
AB  - Chronic pain is a commonly reported problem in primary care, and is Australia's
      third most costly health problem. Despite advances in the understanding and
      treatment of pain, many people with chronic pain do not receive the best
      available care. This paper examines the health care experiences of people with
      chronic pain and focuses discussion on the impact that institutional and cultural
      factors can have on individual experience. Unstructured narrative interviews were
      conducted with a convenience sample of 20 people with chronic pain. Participants'
      experiences pointed to several factors that can affect the outcome of the health
      care they receive, including: the belief that all pain is due to identifiable
      injury or disease; a commitment to finding a diagnosis and cure; problematic
      patient-provider communication; and poor integration of health services.
      Comprehensively addressing these factors cannot be achieved by focusing
      interventions at the individual level. A multifaceted response, which includes
      public health and systemic initiatives, is required. 

PMID- 22950971
TI  - Safety profile of gutless adenovirus vectors delivered into the normal brain
      parenchyma: implications for a glioma phase 1 clinical trial.
AB  - Adenoviral vectors (Ads) have been evaluated in clinical trials for glioma.
      However, systemic immunity against the vectors can hamper therapeutic efficacy.
      We demonstrated that combined immunostimulation and cytotoxic gene therapy
      provides long-term survival in preclinical glioma models. Because helper
      dependent high-capacity Ads (HC-Ads) elicit sustained transgene expression, in
      the presence of antiadenoviral immunity, we engineered HC-Ads encoding
      conditional cytotoxic herpes simplex type 1 thymidine kinase and
      immunostimulatory cytokine Fms-like tyrosine kinase ligand-3 under the control of
      the TetOn system. Escalating doses of combined HC-Ads (1*10(8), 1*10(9), and
      1*10(10) viral particles [VP]) were delivered into the rat brain. We assessed
      neuropathology, biodistribution, transgene expression, systemic toxicity, and
      behavioral impact at acute and chronic time points after vector delivery.
      Histopathological analysis did not reveal any evidence of toxicity or long-term
      inflammation at the lower doses tested. Vector genomes were restricted to the
      injection site. Serum chemistry did not uncover adverse systemic side effects at
      any of the doses tested. Taken together, our data indicate that doses of up to
      1*10(9) VP of each HC-Ad can be safely administered into the normal brain. This
      comprehensive toxicity and biodistribution study will lay the foundations for
      implementation of a phase 1 clinical trial for GBM using HC-Ads.

PMID- 22950974
TI  - The spectrum of aortic pathology in alport syndrome: a case report and review of
      the literature.
AB  - Alport syndrome is an inherited disorder of type IV collagen most commonly
      leading to glomerulonephritis and kidney failure. Various extrarenal
      manifestations have been reported, including a spectrum of aortic and aortic
      valve diseases. We report a case of a 34-year-old man with Alport syndrome
      presenting with chest pain. Work-up showed a dilated aortic root, bicuspid aortic
      valve, aortic insufficiency, and small ascending aortic dissection necessitating
      surgical repair. We provide a review of the literature describing aortic
      pathology in Alport syndrome and suggest that clinicians caring for patients with
      Alport syndrome have a high index of suspicion for such entities in patients
      presenting with symptoms of chest pain.

PMID- 22950975
TI  - Mortality and cardiovascular and bleeding outcomes in patients with CKD receiving
      antiplatelet therapy.

PMID- 22950976
TI  - Effect of branched-chain fatty acids, 3-methylindole and 4-methylphenol on
      consumer sensory scores of grilled lamb meat.
AB  - Tenderness, flavour, overall liking and odour are important components of
      sheepmeat eating quality. Consumer assessment of these attributes has been made
      for carcasses from the Information Nucleus Flock (INF) of the Cooperative
      Research Centre for Sheep Industry Innovation. The concentrations of three
      branched chain fatty acids, 4-methyloctanoic (MOA), 4-ethyloctanoic (EOA) and 4
      methylnonanoic acids (compounds related to 'mutton flavour' in cooked sheepmeat)
      and 3-methylindole and 4-methylphenol (compounds related to 'pastoral' flavour)
      were determined for 178 fat samples taken from INF carcasses. Statistical
      modelling revealed that both MOA and EOA impacted on the 'Like Smell' consumer
      sensory score of the cooked meat product (P<0.05), with increasing concentration
      causing lower consumer acceptance of the product. None of the compounds though
      had an effect on the liking of flavour. Obviously, reducing the effect of MOA and
      EOA on the odour of grilled lamb will improve consumer acceptance of the cooked
      product but other factors affecting the eating quality also need to be
      considered. 

PMID- 22950977
TI  - Quality of fresh and seasoned fat of Cinta Senese pigs as affected by fattening
      with chestnut.
AB  - This trial was aimed to verify the effect of fattening with chestnut on carcass
      characteristics and on quality traits of products of Cinta Senese breed. Thirty
      three Cinta Senese pigs were allotted into three groups. One group was fed a
      commercial feedstuff (0-CH), the other two groups were fed chestnut for one (1
      CH) or three (3-CH) months. Pigs were slaughtered at 130 kg of live weight. The 1
      CH group showed significantly lower pH value at 24h (P<0.05). For sample joint
      dissection a significant effect (P<0.05) of feeding system was found only on
      intermuscular fat, highest in 1-CH. A significant effect of feeding system
      (P<0.05) was found on physical and chemical parameters of Longissimus lumborum:
      the 3-CH group showed the highest values (P<0.05) of L, a, b, drip loss, cooking
      loss, shear force and intramuscular fat on raw meat. The 3-CH showed
      significantly higher level (P<0.05) of unsaturation for the highest percentage of
      MUFA and PUFA.

PMID- 22950978
TI  - Effect of stocking density and group size on growth performance, carcass traits
      and meat quality of outdoor-reared rabbits.
AB  - The effect of stocking density (16 rabbits/m(2), 5 rabbits/m(2), 2.5
      rabbits/m(2), n = 60, Experiment 1) and group size (4 rabbits/cage, 8
      rabbits/cage, 16 rabbits/cage, n = 88, Experiment 2) on productive performance,
      carcass and meat quality of a slow-growing rabbit population reared outdoors was
      investigated in two experiments. The highest stocking density induced the highest
      skin percentage. Lower stocking densities showed lower lightness of Biceps
      femoris and higher redness of Longissimus lumborum muscles. Four rabbits/cage
      group (Experiment 2) showed the highest daily weight gain and slaughter weight
      and the lowest skin percentage. The muscles of 16 rabbits/cage showed
      significantly higher pHu than 8 and 4 rabbits/cage. BF of 16 and 4 rabbits/cage
      showed higher L* value. Productive performance and meat quality of rabbits reared
      outdoors improved in low group size while stocking density needs more
      experiments. The best combination of density, group size and total available
      surface that showed the best production and carcass traits was of 5 rabbits/m(2),
      4 rabbits/cage, and 0.8m(2).

PMID- 22950979
TI  - Sperm capacitation combined with removal of the sperm acrosome and plasma
      membrane enhances paternal nucleus remodelling and early development of bovine
      androgenetic embryos.
AB  - The androgenetic embryo is a useful model for functional analysis of the paternal
      genome during embryogenesis. However, few studies have focused on the factors
      involved in the suppressed developmental competence of such embryos or why sperm
      cloning-derived androgenetic embryos fail to develop beyond the morula stage in
      large domestic animals. To overcome this developmental failure, we tried to
      improve sperm decondensation, as well as to enhance embryonic development by
      sperm capacitation and removal of the acrosome and plasma membrane before
      injection of the spermatozoa. Before injection of the spermatozoa, we quantified
      the effects of sperm capacitation combined with sperm pretreatment on the
      acrosome and plasma membrane status. We also evaluated sperm decondensation
      potential, sperm viability and chromatin integrity. Immunostaining data showed
      that the sperm acrosome and plasma membrane could be more efficiently removed
      after capacitation. Dithiothreitol-induced sperm decondensation potential was
      improved with capacitation and removal of the acrosome and plasma membrane.
      Although most spermatozoa lost viability after pretreatment, their chromatin
      remained integrated. The patterns of paternal chromatin remodelling within
      uncleaved androgenetic embryos and the nucleus morphology of cleaved embryos
      indicated that capacitation combined with membrane disruption could make injected
      spermatozoa decondense synchronously not only with each other, but also with the
      developmental pace of the ooplasm. We successfully produced androgenetic
      blastocysts, and efficiency increased with sperm pretreatment. In conclusion,
      sperm decondensation and the early development of androgenetic embryos were
      enhanced with sperm capacitation and removal of the acrosome and plasma membrane
      prior to sperm injection.

PMID- 22950980
TI  - [Orthostatic hypotension: a potential independent cardiovascular risk factor].

PMID- 22950981
TI  - [Prognosis of giant cell arteritis].
AB  - The short-term prognosis of giant cell arteritis is associated to the risk of
      permanent visual loss, concerning 5-20% of patients, and mainly secondary to
      anterior ischaemic optic neuropathy. Most studies have suggested that long-term
      survival, around 80% at 5 years, is not impaired in giant cell arteritis.
      However, increased mortality has been often noticed in the year following
      diagnosis, especially related to cardiovascular disorders including aortitis (10
      20% of cases), stroke (5-10% of cases), or myocardial infarction, commonly
      associated to atherosclerosis and to arterial hypertension. Aortic dissections or
      aneurysm ruptures are causes of death, which can therefore be directly related to
      the vasculitis. Most of the patients develop steroid related complications:
      infections that may lead to death, or osteoporosis in 20-40% of cases with a
      better prognosis than before thanks to preventive treatments.

PMID- 22950982
TI  - Screening for anal neoplasia: anal cytology - sampling, processing and reporting.
AB  - Anorectal cytology (ARC) is increasingly accepted as a valid screening tool for
      the diagnosis of squamous intraepithelial lesions in populations at increased
      risk for anal cancer. As with cervical cancer screening protocols, proper patient
      preparation, specimen collection and specimen processing are essential for
      obtaining an optimal cytological sample. With attention and experience, the
      clinician can collect the best possible ARC specimen for laboratory evaluation.
      The incorporation of repeated interval anal cytology into standard surveillance
      practices for high-risk individuals is a valuable tool for the early detection of
      human papillomavirus-related anal squamous epithelial lesions and the prevention
      of anal squamous cell carcinomas.

PMID- 22950983
TI  - Selective and potent urea inhibitors of cryptosporidium parvum inosine 5'
      monophosphate dehydrogenase.
AB  - Cryptosporidium parvum  and related species are zoonotic intracellular parasites
      of the intestine.  Cryptosporidium  is a leading cause of diarrhea in small
      children around the world. Infection can cause severe pathology in children and
      immunocompromised patients. This waterborne parasite is resistant to common
      methods of water treatment and therefore a prominent threat to drinking and
      recreation water even in countries with strong water safety systems. The drugs
      currently used to combat these organisms are ineffective. Genomic analysis
      revealed that the parasite relies solely on inosine-5'-monophosphate
      dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we
      report a selective urea-based inhibitor of  C. parvum  IMPDH (CpIMPDH) identified
      by high-throughput screening. We performed a SAR study of these inhibitors with
      some analogues exhibiting high potency (IC(50) < 2 nM) against CpIMPDH, excellent
      selectivity >1000-fold versus human IMPDH type 2 and good stability in mouse
      liver microsomes. A subset of inhibitors also displayed potent antiparasitic
      activity in a  Toxoplasma gondii  model.

PMID- 22950984
TI  - Insecticidal management and movement of the brown stink bug, Euschistus servus,
      in corn.
AB  - In eastern North Carolina, some brown stink bugs, Euschistus servus (Say)
      (Hemiptera: Pentatomidae) are suspected to pass the F(1) generation in wheat
      (Triticum aestivum L.) (Poales: Poaceae) before moving into corn (Zea mays L.)
      (Poales: Poaceae). These pests can injure corn ears as they develop. To test
      their effectiveness as a management tactic, pyrethroids were aerially applied to
      field corn in two experiments, one with 0.77 ha plots and another with 85 ha
      plots. Euschistus servus population abundance was monitored over time in both
      experiments and yield was assessed in the larger of the two experiments. In the
      smaller experiment, the populations were spatially monitored in a 6.3 ha area of
      corn adjacent to a recently harvested wheat field (352 sampling points of 6.1 row
      meters in all but the first sampling event). Overall E. servus abundance
      decreased throughout the monitoring period in the sampling area of the smaller
      experiment, but remained unchanged over time in the large-scale experiment.
      During all sampling periods in both experiments, abundance was the same between
      treatments. Yield was unaffected by treatment where it was measured in the larger
      experiment. In the smaller experiment, E. servus were initially aggregated at the
      field edge of the corn (two, six and 13 days following the wheat harvest).
      Sixteen days following the wheat harvest they were randomly distributed in the
      corn. Although it was not directly measured, stink bugs are suspected to move the
      cornfield edge as a result of the adjacent wheat harvest. More study of the
      biology of E. servus is needed, specifically in the area of host preference,
      phenology and movement to explain these phenomena and to produce better
      management strategies for these pests.

PMID- 22950985
TI  - Pharmacokinetic and pharmacogenetic analysis of oral busulfan in stem cell
      transplantation: prediction of poor drug metabolism to prevent drug toxicity.
AB  - High dose busulfan (BU) has become a mainstay in conditioning regimens for
      hematopoietic stem cell transplantation (HSCT), despite its unpredictable
      response, narrow therapeutic index and severe toxicity. The present study
      provides an integration of pharmacokinetic and genetic data of 63 adults with
      acute myeloid leukemia (AML) preconditioned for HSCT with high dose oral BU, with
      the aim of defining biomarkers predictive of poor BU metabolism. BU area under
      the concentration time curve (AUC) demonstrated that 76% of the patients achieved
      target AUC; 24% required dose modification. The main findings of this study were:
      (1) AML patients carrying the GSTP1 rs1695 variant allele were at risk of
      developing supra-therapeutic BU-AUC due to reduced BU clearance. (2) Combined
      polymorphisms in GSTM1 and ABCB1 were associated with BU clearance and AUC rates.
      In conclusion, GST and ABCB1 genotyping may assist care-givers in personalizing
      BU dosage with less trial-and-error and may enable preemptive identification of
      patients at risk for BU toxicity.

PMID- 22950986
TI  - Subungueal haemorrhages following docetaxel (taxotere) treatment.
AB  - INTRODUCTION: Docetaxel belongs to the taxane group of chemotherapeutic agents
      used in the management of various malignant diseases. Nail changes as a
      complication of such treatment are observed in about 44%. Subungual haemorrhages
      (SH), are very rare following docetaxel therapy and only a few cases have been
      previously reported. OBSERVATION: An 80-year-old man suffering from prostate
      adenocarcinoma was treated with a 3-weekly cure of docetaxel started 3 months
      earlier. Nail changes occurred after the 5th cycle of docetaxel. Clinical
      examination revealed orange discoloration of the nail plates, subungueal
      haemorrhages (SH) and onycholysis involving nails of all the digits and toenails
      of both hands and feet. These features were highly suggestive of nail toxicity
      following docetaxel therapy. DISCUSSION: Nail changes secondary to Taxane
      chemotherapy includes nail bed dyschromia, onycholysis, red or orange Beau's
      lines and subungueal hyperkeratosis. SH, as reported in this case, is related to
      the cumulative dose of docetaxel and should not be attributed to other systemic
      diseases. Clinicians should recognize this complication to avoid abusive
      treatment or investigations and inform the patients about the possibility of nail
      changes secondary to taxane drugs.

PMID- 22950987
TI  - Comparison of methods for the detection of medication safety events in the
      critically ill.
AB  - PURPOSE: To categorize and synthesize medication safety event detection methods
      in the critically ill in order to provide clinicians and administrators with
      approaches to event detection that are intended to expand and complement
      traditional voluntary reporting systems. METHODS: A literature search of
      OvidMEDLINE was performed to identify articles related to medication safety
      involving critically ill patients in the intensive care unit setting. The
      inclusion of articles was restricted to comparative studies. The bibliographies
      of all retrieved articles were reviewed to obtain additional articles of
      relevance. The various event detection methods were compared by: evidence
      supporting their use; number, type and severity of events detected; phase of the
      medication use process in which events were detected; and ease and cost of
      implementation. Major limitations of each method were also collated. RESULTS:
      There are a number of methods that can be used to identify medication safety
      events in the critically ill. These can broadly be categorized as: 1) voluntary
      reporting, 2) record review, 3) rules/triggers and 4) direct observation and 5)
      interviews/surveys. Relatively few studies have directly compared these
      assessment methods in the ICU setting, although the limitations of the
      traditional voluntary reporting system as the sole method of event detection are
      well established. Although not truly dichotomous, these methods can be broken
      down into more proactive and reactive approaches. Rules/triggers and direct
      observation of the medication use process in the ICU are examples of proactive
      approaches to event detection, while the traditional unsolicited voluntary
      reporting is typically reactive. However, each of the event detection methods has
      advantages and disadvantages, so the methods should not be considered mutually
      exclusive with respect to obtaining information about medication safety.
      CONCLUSIONS: Given the limitations of traditional voluntary reporting systems, a
      multimodal approach used to identify medication safety events is most likely to
      capture the largest number and type of events. We would advise not trying to
      implement additional approaches beyond voluntary reporting systems all at once.
      This would be difficult and costly. Rather, we suggest a systematic
      implementation of additional event detection approaches that takes into account
      hospital-specific considerations.

PMID- 22950988
TI  - Effects of filtration on the presence of particulate and oxycodone content of
      injections prepared from crushed OxyContin(r) tablets.
AB  - It is common for injecting drug users (IDU) to prepare injections by crushing
      tablets which are not designed for parental administration. The injection of
      insoluble tablet excipients can lead to serious local and systemic medical
      complications. The aim of the study was to investigate the effectiveness of
      various types of filters in removing harmful insoluble particles from the
      injections prepared using crushed oxycodone tablets. Injections were prepared
      from a sustained-release oxycodone tablet formulation. The filtration of tablet
      extracts was carried out following procedures used by IDU using makeshift filter
      and commercially available filters. Particulate contamination and oxycodone
      content were analysed using light microscopy and spectrophotometer. Unfiltered
      extracts contained hundreds of thousands of particles of sufficient size to cause
      harms. Cigarette filters removed large particles but failed to remove small
      particles. The combination of cigarette filter and syringe filter (0.45 MUm or
      0.22 MUm) reduced the particle count by 90 - 95%. A double membrane syringe
      filter (0.8/0.2 MUm) removed more than 99% of the particles. Recovery of
      oxycodone was more than 95% with the tested syringe filters. Particulate
      contamination in injections prepared from crushed tablets can be effectively
      removed using a combination process of cigarette filter and syringe filters, or a
      0.8/0.2 MUm syringe filter. Compared to other filters, the 0.8/0.2 MUm syringe
      filter did not block, the filtration was quick and easy to perform, and did not
      retain oxycodone. The use of a 0.8/0.2 MUm syringe filter can provide an
      important harm reduction measure for IDU.

PMID- 22950989
TI  - Comparison of melatonin and ozone in the prevention of reperfusion injury
      following unilateral testicular torsion in rats.
AB  - OBJECTIVE: To compare the efficacy of ozone with melatonin, shown as the most
      powerful antioxidant in attenuation of testicular ischemia/reperfusion injury, in
      an experimental rat model of testicular torsion/detorsion. METHODS: Twenty-four
      male Wistar rats were divided into 4 groups: sham-operated, torsion/detorsion,
      torsion/detorsion plus melatonin, and torsion/detorsion plus ozone. Melatonin (10
      mg/kg) and ozone (4 mg/kg) were intraperitoneally injected daily beginning 15
      minutes before detorsion for the following 7 days. At the seventh day, blood and
      tissue samples were obtained. Johnsen score, malondialdehyde, inhibin B,
      glutathione plasma total sulfhydryl group (RSH) levels, and total nitric oxide
      were studied. RESULTS: Torsion/detorsion caused increase in tissue
      malondialdehyde and total nitric oxide along with a decrease in Johnsen score,
      tissue and plasma inhibin B, RSH, and glutathione levels. Melatonin prevented the
      rise in malondialdehyde and total nitric oxide levels and improved Johnsen score,
      tissue and plasma inhibin B, and tissue glutathione levels, along with a decrease
      in plasma RSH level. Ozone showed similar results except for the total nitric
      oxide level. Concomitantly, in contralateral testis, melatonin and ozone induced
      similar changes for Johnsen score, malondialdehyde, and inhibin B (not
      significant) and in glutathione (significant). Melatonin decreased the total
      nitric oxide level in both testes and ozone increased the same parameter.
      CONCLUSION: On different pathways, ozone was comparable with melatonin in the
      amelioration of ischemia/reperfusion injury. Protective effects of ozone were
      associated with nitrous oxide. The potential for ozone as a treatment for
      torsion/detorsion therefore deserves to be further elucidated.

PMID- 22950990
TI  - Proximal hypospadias: effect of urethral plate mobilization on release of
      chordee.
AB  - OBJECTIVE: To accurately measure the correction obtained by the release of the
      skin and dartos fascia and that obtained by mobilization of the urethral plate
      and resection of the underlying fibrous tissue (according to Koyanagi and
      Mollard), in the release of chordee. METHODS: From February 1996 to February
      2011, 234 patients underwent surgery for proximal hypospadias by 1 surgeon.
      Lateral photographs were taken during successive saline erection tests for 205
      patients. The first test was performed at the beginning of the operation, the
      second test after the release of the skin and dartos fascia, the third test after
      possible mobilization of the urethral plate and resection of the underlying
      fibrous tissue, and the last test at the end of surgery. RESULTS: Preservation of
      the urethral plate was possible in 191 patients (93%). Analysis of the lateral
      photographs showed that stripping of the penis resulted in complete correction of
      all chordee <45 degrees . For curvature >90 degrees , stripping of the penis was
      insufficient in 88% of the cases. However, mobilization of the urethral plate
      with resection of the underlying fibrous tissue resulted in very low correction
      (10 degrees -20 degrees ), although the blood supply to this plate was preserved.
      CONCLUSION: The results of the present study have shown that correction of the
      curvature that accompanies proximal hypospadias is obtained mainly by release of
      the skin and dartos fascia.

PMID- 22950991
TI  - Confocal laser endomicroscopy of bladder tumors associated with photodynamic
      diagnosis: an ex vivo pilot study.
AB  - OBJECTIVE: To improve the sensitivity of white light cystoscopy, photodynamic
      diagnosis (PDD) is useful but has low specificity. Recently, confocal laser
      endomicroscopy (CLE) has been used for the diagnosis of urothelial cell
      carcinoma. The main objective was to examine the feasibility of simultaneous PDD
      and CLE. A secondary objective was to determine whether hexyl aminolevulinic acid
      (HAL) can be used just as fluorescein for CLE. METHODS: In the present
      prospective single-center study with a same-patient comparison, patients with
      suspected urothelial cell carcinoma underwent surgical exploration after
      receiving a bladder instillation of HAL. After resection of suspected lesions
      under blue light, the samples were inspected ex vivo using CLE with and without
      fluorescein. Simultaneous blue light CLE inspection was performed. All samples
      were then transferred to the pathology laboratory for the classic analysis.
      RESULTS: Of the 12 patients studied, blue light cystoscopy revealed suspect
      lesions in 11; 10 had pathology proven urothelial cell carcinoma. CLE analysis
      was not modified by sample exposure to blue light, which facilitated orientation
      of the fiber toward the suspect red fluorescence areas. The fluorescence obtained
      with HAL-CLE was insufficient for microscopic histologic analysis, unlike the
      resolution obtained with fluorescein. Comparing CLE and the pathologic findings
      was possible and conclusive for 4 of 12 samples. CONCLUSION: Combining PDD and
      CLE ex vivo demonstrated the usefulness of HAL for guiding blue light CLE. HAL
      was insufficient to allow histologic CLE, which required the use of fluorescein.
      The results of this pilot study have indicated the feasibility of CLE. However,
      an in vivo method incorporating fluorescein and PDD will be required to improve
      the diagnostic specificity of PDD alone.

PMID- 22950992
TI  - The effect of 5-aminolevulinic acid and its derivatives on protoporphyrin IX
      accumulation and apoptotic cell death in castrate-resistant prostate cancer
      cells.
AB  - OBJECTIVE: To examine whether pharmacologically relevant zinc-binding agents are
      capable of depleting X-linked inhibitor of apoptosis protein in tumor cells. Our
      prior work reveals that treatment with zinc-chelating agents induces selective
      downregulation of the X-linked inhibitor of apoptosis protein in cancer cells of
      various origins. A precursor of the heme synthetic pathway, 5-aminolevulinic
      acid, is metabolized to protoporphyrin IX, which is highly reactive with zinc. We
      assessed whether modified versions of 5-aminolevulinic acid with lipophilic side
      chains can enhance efficacy and selectivity with respect to protoporphyrin IX
      accumulation, X-linked inhibitor of apoptosis protein depletion, and tumor
      necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human
      castration-resistant prostate cancer cells. METHODS: Seven modified versions of 5
      aminolevulinic acid (5 esters and 2 amides) were synthesized. Levels of
      endogenous protoporphyrin IX were examined by flow cytometry. X-linked inhibitor
      of apoptosis protein expression was examined by Western blotting. terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay was used
      to assess cell apoptosis. Results were compared qualitatively. RESULTS:
      Accumulation of endogenous protoporphyrin IX by castration-resistant prostate
      cancer cells was shown to be directly related to the carbon chain length of the
      esterified 5-aminolevulinic acid derivatives. In fact, treatment with 5
      aminolevulinic acid-HE was superior to that achieved by 5-aminolevulinic acid
      with respect to X-linked inhibitor of apoptosis protein downregulation. 5
      aminolevulinic acid and 5-aminolevulinic acid-HE in combination with tumor
      necrosis factor-related apoptosis-inducing ligand significantly enhanced
      apoptotic cell death in castration-resistant prostate cancer cell lines.
      CONCLUSION: Esterified derivatives of 5-aminolevulinic acid alone or in
      combination with other agents may provide therapeutic opportunities in the
      treatment of castration-resistant prostate cancer by harnessing apoptotic
      pathways that are triggered by cellular zinc imbalance.

PMID- 22950993
TI  - Clinical characteristics and reproductive outcomes in infertile men with
      testicular early and late maturation arrest.
AB  - OBJECTIVE: To compare the clinical characteristics and reproductive outcomes of
      nonobstructive azoospermic men with uniform early and late maturation arrest.
      METHODS: Patients with biopsy-documented uniform maturation arrest undergoing
      testicular sperm retrieval and complete medical records were enrolled in the
      present study. Their medical history, physical examination findings, testicular
      volume, serum hormone parameters, genetic anomalies, sperm retrieval, and
      reproductive outcomes were retrospectively analyzed. RESULTS: In a cohort of 223
      nonobstructive azoospermic men, 34 men with uniform maturation arrest (21 early
      maturation arrest and 13 late maturation arrest) were identified. No significant
      differences were seen in the age distribution, testicular volume, or hormone
      parameters between patients with early and late maturation arrest. Only 13
      patients (38.2%) had a normal serum follicle-stimulating hormone level and normal
      testicular volume. Patients with early maturation arrest had a greater frequency
      of overall genetic anomalies, and patients with late maturation arrest had a
      greater frequency of previous testicular insults. The sperm retrieval and
      impregnation rate were nonsignificantly greater in patients with late maturation
      arrest. CONCLUSION: Maturation arrest has a variety of causes and presents with
      diverse phenotypes. Not all patients with uniform maturation arrest have a normal
      follicle-stimulating hormone level or testicular volume. Patients with early
      maturation arrest have a greater incidence of genetic anomalies and are more
      likely to have worse reproductive outcomes than are patients with late maturation
      arrest.

PMID- 22950995
TI  - Editorial comment.

PMID- 22950996
TI  - Assessment of rates of lymph nodes and lymph node metastases in periprostatic fat
      pads in a consecutive cohort treated with retropubic radical prostatectomy.
AB  - OBJECTIVE: To determine the rates of lymph nodes and lymph node metastases in
      periprostatic fat pads yielded during exposure of the anterior surface of the
      dorsal vein complex, puboprostatic ligaments, and endopelvic fascia during
      radical prostatectomy. METHODS: Histopathologic examination was performed in 356
      patients who underwent radical prostatectomy between July 2010 and September 2010
      at a single institution. Separate histologic work-up of the periprostatic fat
      pads addressed the presence of lymph nodes and possible metastatic invasion of
      lymph nodes within this area. Descriptive analyses and multivariable analyses to
      predict the presence of lymph node metastases within these fat pads were
      performed. RESULTS: Lymph nodes within periprostatic fat pads were detected in 19
      (5.5%) patients. Among these patients, tumor infiltration was found in 4 (1.2%).
      Three of these 4 patients harbored lymph node metastases without any other lymph
      node metastasis during standard lymphadenectomy. No relationship was detected
      between the total number of lymph nodes removed and the detection of lymph nodes
      within periprostatic fat pads (P = .6). CONCLUSION: Our analysis demonstrates
      that periprostatic fat pads harbor lymph nodes. No relationship between the
      presence of lymph node metastases in periprostatic fat pads and the presence of
      lymph node metastases in other areas was found. Similarly, no relationship exists
      between the presence of lymph nodes in this area and the total number of lymph
      nodes yielded in other lymphatic fields. Therefore, for guaranteeing precise
      lymph node staging, implementing routinely pathologic work-up of periprostatic
      fat pads yielded during radical prostatectomy should be considered.

PMID- 22950997
TI  - Differences in frequency of ERG oncoprotein expression between index tumors of
      Caucasian and African American patients with prostate cancer.
AB  - OBJECTIVE: To systematically evaluate the ETS-related gene (ERG) alterations in
      the multifocal tumor context using whole-mount prostatectomy specimens from
      African and Caucasian American patients matched for age, pathologic grade and
      stage. Oncogenic activation of the ERG is the most common early genomic
      alteration in patients with prostate cancer (CaP) in Western countries. However,
      ERG alterations have not been systematically examined in African American
      patients with a known greater risk of CaP incidence and mortality. METHODS: ERG
      oncoprotein expression was analyzed in 91 Caucasian and 91 African American
      patients with CaP, who were matched for age, Gleason score, and pathologic stage.
      A unique aspect of the present study was the evaluation of ERG in whole-mount
      prostatectomy sections, minimizing sampling bias and allowing the careful
      assessment of the ERG in the multifocal tumor context of CaP. RESULTS: The
      frequency of ERG-positive prostate tumors was significantly greater among
      Caucasian Americans than among African Americans when assessed in all tumor foci
      (41.9% vs 23.9%, P < .0001). A markedly greater frequency of ERG oncoprotein
      expression was noted between the index tumors of the Caucasian Americans (63.3%)
      and those of the African Americans (28.6%). Also, in the African American
      patients, the higher grade index tumors were predominantly ERG negative.
      CONCLUSION: ERG typing of CaP established a major difference between the index
      tumors of Caucasian and African American patients. ERG-negative index tumors
      might indicate a less favorable outcome for African American patients. The
      results of the present study underscore that typing of CaP for the ERG could
      enhance our understanding of the biologic differences between the examined ethnic
      groups.

PMID- 22950998
TI  - Fluoro-less ureteral stent placement following uncomplicated ureteroscopic stone
      removal: a feasibility study.
AB  - OBJECTIVE: To test the feasibility of ureteral stent placement without image
      guidance after uncomplicated ureteral stone removal and to compare the outcomes
      of fluoro-less and conventional ureteral stent placement. METHODS: A technique
      was devised to allow placement of a ureteral stent without image guidance by
      substituting fluoroscopy with visual and tactile cues. A retrospective review of
      25 patients using fluoro-less stent placement was compared with 25 consecutive
      patients who underwent conventional stent placement with fluoroscopy. Stent
      placement was graded on a 6-point scale to assess coil symmetry and location.
      Comparisons between the fluoro-less stent placements and controls were performed
      with the Mann-Whitney U test. All hypotheses were 2-sided and conducted at an
      alpha level of 0.05. RESULTS: All 25 ureteral stent placements were performed
      successfully without the use of fluoroscopy for image guidance. There was no
      significant difference in age, gender, body mass index, stone size, or
      complication rates when fluoro-less and conventional stent placements were
      compared. In addition, grade 1 placement was achieved in 76% of the fluoro-less
      group and in 64% of the conventional group. Although placement accuracy was
      higher in the fluoro-less group this was not statistically significant (P = .13).
      CONCLUSION: Ureteral stent placement without fluoroscopic guidance is feasible.
      It maintains comparable efficacy and complication rates with conventional
      ureteral stent placement. This technique allows reduced radiation exposure in
      patients requiring ureteral stent placement.

PMID- 22950999
TI  - Activation of VEGF and ERK1/2 and improvement of urethral function by adipose
      derived stem cells in a rat stress urinary incontinence model.
AB  - OBJECTIVE: To investigate the injected autologous adipose-derived stem cells
      (ADSCs) in improving stress urinary incontinence in a rodent model of parturition
      related stress incontinence and the possible mechanism. METHODS: The 40 rats were
      developed stress urinary incontinence models by postpartum balloon dilation of
      the vagina for 4 hours followed by bilateral ovariectomy. ADSCs were isolated
      from the peri-ovarian fat and labeled with thymidine analog 5-ethynyl-2
      deoxyuridine (EdU). Twenty stress urinary incontinence rats received peri
      urethral injection of phosphate-buffered saline as the negative controls and the
      other 20 stress urinary incontinence rats received peri-urethral injection of EdU
      labeled ADSCc. Twenty control rats underwent sham ovariectomy without balloon
      dilation and served as positive controls. Four weeks later, voiding function was
      assessed by cystometry. Urethral histologic examination (Masson trichrome stain,
      picrosirius red stain, Hart elastin stain, Gordon and Sweet stain, and
      immunohistochemical stain) and Western blot were performed on urethral tissues.
      RESULTS: Both leak point pressure and bladder capacity were significantly
      increased in ADSC-treated rats, compared to the balloon-injured ovariectomized
      rats. Histologic examination revealed normalized appearance of the fibromuscular
      structure of the urethra as well as increased peri-urethral blood vessel density
      in ADSC-treated rats. On Western blot, vascular endothelial growth factor and P
      extracellular signal-regulated kinases (ERKs)1/2 protein was expressed at a
      higher rate in tissues from ADSC-treated rats compared to phosphate-buffered
      saline-treated rats. CONCLUSION: Peri-urethral injection of ADSCs is associated
      with more normal urinary function and urethral structure in rats with parturition
      related incontinence. The activation of vascular endothelial growth factor and
      ERK1/2 may be responsible for the paracrine effects from ADSCs.

PMID- 22951000
TI  - The protective effects of spirulina in cyclophosphamide induced nephrotoxicity
      and urotoxicity in rats.
AB  - OBJECTIVE: To evaluate the role of Spirulina, a blue-green algae with antioxidant
      properties in the protection of cyclophosphamide-induced nephrotoxicity and
      hemorrhagic cystitis in rats. METHODS: The control group (C) was sacrificed 24
      hours after being given a single dose of saline intraperitoneally (150 mg/kg) on
      the seventh day of the experiment. The rats in the second group (CP) were
      sacrificed 24 hours after being given a single dose of cyclophosphamide,
      intraperitoneally (150 mg/kg) on the seventh day of the experiment. Spirulina was
      administered to the third group (SP+CP) orally (1000 mg/kg bw/day) for 7 days and
      a single dose of cyclophosphamide was injected intraperitoneally (150 mg/kg) on
      the seventh day of the experiment. At the eighth day of the experiment,
      malondialdehyde, superoxide dismutase, and catalase levels in renal and urinary
      bladder tissues were measured. Histomorphology in urinary bladder, apoptosis by
      caspase 3 immunostaining, and TUNEL assay in kidney were also evaluated. RESULTS:
      Tissue levels of malondialdehyde in the SP+CP group were significantly lower
      versus CP group (P < .05). Tissue levels of superoxide dismutase and catalase in
      the SP+CP group were significantly higher vs the CP group (P < .05). The
      histomorphologic alteration in urinary bladder in the SP+CP group was
      significantly lower vs that in the CP group. In the kidney, apoptosis in the
      SP+CP group as shown with TUNEL assay and immunohistochemistry was significantly
      lower vs that in the CP group (P < .05). CONCLUSION: Pretreatment with Spirulina
      protects the rats from cyclophosphamide-induced nephro-urotoxicity via its
      antioxidant and anti-apoptotic properties.

PMID- 22951001
TI  - Effects of high glucose on human cavernous endothelial cells.
AB  - OBJECTIVE: To obtain experimental evidence for a causal effect of high glucose
      (HG) on cavernous endothelial dysfunction. METHODS: Cavernous tissues were
      obtained from patients undergoing surgery for penile prosthesis implantation.
      Endothelial cells were isolated by binding to anti-CD31 antibody, followed by
      magnetic capture. Their endothelial identity was verified by flow cytometry and
      immunofluorescence staining for endothelial markers CD31, von Willebrand factor,
      and endothelial nitric oxide synthase, and by their ability to form tube-like
      structures in matrigel (tube formation) and to endocytose acetylated low-density
      lipoprotein (low-density lipoprotein uptake). The cells were then cultured under
      normal glucose (NG) (5 mM) or HG (25 mM) conditions, followed by analysis for
      endothelial gene expression, function, proliferation, apoptosis, and
      mitochondrial fragmentation. RESULTS: Human cavernous endothelial cell (HCEC)
      strains were established and determined to be nearly 100% pure endothelial cells.
      In the HG culture condition, HCECs expressed approximately 50% less CD31, von
      Willebrand factor, and endothelial nitric oxide synthase, but nearly twice as
      much collagen IV compared with HCECs grown in NG medium. HG also suppressed low
      density lipoprotein uptake and tube formation by approximately 50%. HCECs grew
      significantly slower in the high-glucose medium than in the NG medium.
      Approximately 3 times as many cells exhibited apoptosis in the HG medium as in
      the NG medium. Approximately 4 times as many cells contained fragmented
      mitochondria in the HG medium as in the NG medium. CONCLUSION: HG caused a
      decrease in endothelial proliferation, function, and marker expression. It also
      caused an increase in endothelial collagen IV expression, apoptosis, and
      mitochondrial fragmentation. Together, these HG-induced changes in cavernous
      endothelial cells provide an explanation for hyperglycemia's detrimental effects
      on erectile function.

PMID- 22951002
TI  - A case series of genital vascular anomalies in children and their management:
      lessons learned.
AB  - OBJECTIVE: To review our experience with genital vascular anomalies and discuss
      the management considerations for patients with associated genitourinary defects.
      METHODS: We reviewed the presentation, course, management considerations,
      surgical treatment, and follow-up of all cases of genital vascular anomalies
      treated at a single institution from January 2008 to October 2011. The lesions
      were classified according to the International Society for the Study of Vascular
      Anomalies. All patients were boys <18 years old. RESULTS: We identified 3
      patients with genital vascular anomalies. Of these 3 patients, 2 had an infantile
      hemangioma and 1 had a venous malformation. All lesions were identifiable on
      physical examination, and 2 of the patients presented within a few months of
      birth. One patient had associated genitourinary abnormalities that complicated
      his treatment. Scrotal ultrasonography and pelvic magnetic resonance imaging
      consistently showed the vascular anomalies to be highly vascular and distinct
      from the underlying testes. Both intrascrotal lesions were excised, and the
      cutaneous lesion was excised as a part of a larger genitourinary reconstruction.
      At a mean follow-up of 33 months (range 23-42), the intrascrotal infantile
      hemangioma had recurred, requiring repeat intervention, but the cutaneous
      hemangioma had not. CONCLUSION: Vascular anomalies of the male genitalia are
      rare. Pelvic magnetic resonance imaging is useful for characterizing the internal
      extent of vascular anomalies and ultrasonography is useful in monitoring these
      lesions over time. The timing of surgery and the high recurrence rate are
      important considerations when planning surgical resection of genital vascular
      anomalies, especially when associated with concomitant genitourinary defects.

PMID- 22951003
TI  - Expression pattern of testicular claudin-11 in infertile men.
AB  - OBJECTIVE: To investigate the expression levels of claudin-11 mRNA and the
      localization of claudin-11 protein in testes of infertile men. METHODS: This
      study included 5 men with obstructive azoospermia and 50 men with nonobstructive
      azoospermia who had undergone testicular sperm extraction. Testicular tissues
      were obtained from these men and expression levels of claudin-11 mRNA in
      testicular samples were determined by real-time reverse transcription-polymerase
      chain reaction. The localization of claudin-11 protein was analyzed by
      immunofluorescent staining. RESULTS: Expression levels of testicular claudin-11
      mRNA in nonobstructive azoospermia men were significantly greater than in
      obstructive azoospermia men, whereas there was no significant difference in
      testicular claudin-11 mRNA expression between men with and without successful
      sperm retrieval by testicular sperm extraction. Based on the findings of
      immunofluorescent staining, expression patterns of claudin-11 protein could be
      divided into normal (localization to basal component of seminiferous tubules) and
      abnormal patterns (diffuse expression in Sertoli cells/extremely low or no
      expression). The proportion of nonobstructive azoospermia men with an abnormal
      expression pattern of claudin-11, particularly that of Sertoli cell-only syndrome
      men, was significantly greater than that of obstructive azoospermia men.
      Furthermore, claudin-11 expression showing an abnormal pattern in men without
      successful sperm retrieval was significantly frequent compared with those whose
      sperm were successfully retrieved. CONCLUSION: These findings suggest that
      disorganization of claudin-11 expression in Sertoli cells might be one of the
      factors involved in the impairment of spermatogenesis.

PMID- 22951004
TI  - Scrotal metastasis from a nonmuscle-infiltrative bladder cancer: a surprising
      clinical evolution.

PMID- 22951005
TI  - Inhibitory effect of somatostatin receptor subtype-4 agonist NNC 26-9100 on
      micturition reflex in rats.
AB  - OBJECTIVE: To investigate the effects of activation of somatostatin subtype 4
      (SST4) on the micturition reflex in rats. METHODS: Continuous cystometrograms
      (0.04 mL/min infusion rate) were performed in female Sprague-Dawley rats (242-265
      g) under urethane anesthesia. After stable micturition cycles were established, a
      selective SST4 receptor agonist, NNC 26-9100, was administered intravenously in
      normal rats or rats pretreated with capsaicin 4 days before the experiments. The
      micturition parameters were recorded and compared before and after drug
      administration. RESULTS: Intravenous administration of NNC 26-9100 (10-300
      MUg/kg) significantly increased the intercontraction interval in a dose-dependent
      fashion. Intravenous administration of NNC 26-9100 (10-300 MUg/kg) also
      significantly increased the pressure threshold in a dose-dependent fashion. No
      significant changes were seen in the baseline pressure, maximum voiding pressure,
      or postvoid residual urine volume. However, NNC 26-9100-induced increases in the
      intercontraction intervals and pressure threshold were not seen in rats with C
      fiber desensitization induced by capsaicin pretreatment. CONCLUSION: These
      results indicate that in urethane-anesthetized rats, activation of the SST4
      receptor can inhibit the micturition reflex by suppression of capsaicin-sensitive
      C-fiber afferent pathways. Thus, the SST4 receptor could be a potential target
      for the treatment of C-fiber afferent-mediated bladder dysfunction.

PMID- 22951006
TI  - An unusual case of chromophobe RCC: presented with an inferior vena cava thrombus
      and liver metastases and no discernible mass within the kidney on computerized
      tomography images.
AB  - A 57-year-old female with fatigue presented to our hospital. High-quality
      contrasted abdominal computerized tomography images demonstrated extensive
      filling defect within the left renal vein and the inferior vena cava and an
      enhancing hepatic mass with no obvious mass lesion in the left kidney. The
      patient underwent a total resection of the left kidney and venous thrombectomy by
      open surgery; intraoperative hepatic mass biopsy with frozen section confirmed a
      metastatic disease and right hepalobectomy was conducted in one surgical session.
      Histopathologic examination revealed a lesion of chromophobe renal cell carcinoma
      within the left kidney.

PMID- 22951007
TI  - Midline extraperitoneal approach for retroperitoneal lymph node dissection for
      testicular germ cell tumor.
AB  - INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) for the treatment of
      testicular germ cell tumor is technically difficult and associated with
      significant morbidity. We postulated that a novel midline extraperitoneal (EP)
      approach might minimize the morbidity. TECHNICAL CONSIDERATIONS: We describe a
      midline extraperitoneal approach in detail. The operative time, estimated blood
      loss, lymph node yield, return of bowel function, length of stay, and
      postoperative complications were retrospectively reviewed. From April 2010 to May
      2011, 12 consecutive patients underwent EP-RPLND at 2 tertiary centers by a
      single surgeon, including 5 primary and 7 postchemotherapy RPLNDs. The clinical
      characteristics and outcomes were compared with those from a matched cohort of
      transperitoneal-RPLND patients. RESULTS: The median follow-up was 173 and 201
      days in the EP and transperitoneal groups, respectively. The EP group had a
      shorter mean operative time of 292 versus 337 minutes (P = .02) and lower
      estimated blood loss of 305 versus 575 mL (P = .05). More lymph nodes were
      retrieved in the EP group (44 vs 27 nodes, P = .0006). Finally, an earlier return
      of bowel function (1.7 vs 2.9 days, P = .0001) and a shorter median length of
      stay (3.3 vs 5.3 days, P = .0001) was seen in the EP group. CONCLUSION: EP-RPLND
      can be performed safely without prolonged operative times or compromised lymph
      node retrieval, even in the postchemotherapy setting, and is associated with a
      faster return of bowel function and shortened length of stay.

PMID- 22951008
TI  - Factors affecting renal function after open partial nephrectomy-a comparison of
      clampless and clamped warm ischemic technique.
AB  - OBJECTIVE: To analyze factors impacting postoperative renal function after open
      partial nephrectomy using both the clampless and clamped warm-ischemic technique.
      METHODS: We studied a cohort of patients who underwent clamped partial
      nephrectomy (n = 164) and clampless partial nephrectomy (n = 64) from March 2002
      to March 2009 with >= 12-months follow-up. Clamped partial nephrectomy used hilar
      occlusion before resection. Clampless partial nephrectomy used focal radio
      frequency coagulation to facilitate hemostasis before resection, nonischemic
      dissection/resection with hydro-dissection, or sharp resection after local
      compression. Demographics, tumor characteristics/RENAL nephrometry scores,
      perioperative variables, and complications were compared between the two methods.
      Multivariable analysis was performed to identify factors predicting de novo
      estimated glomerular filtration rate <60. RESULTS: Patient characteristics were
      similar between groups. Mean RENAL score was greater in clamped (6.9) vs
      clampless (6.4, P = .026); complications (P = .430) and urine leaks (clampless
      partial nephrectomy 3.1% vs clamped-PN 7.3%, P = .360) were similar. Mean warm
      ischemia time (min) was 24.5 for clamped partial nephrectomy. De novo estimated
      glomerular filtration rate <60(%) at last follow up was 13.5 (clamped) vs 3.1
      (clampless) (P = .071). Multivariable analysis of the entire cohort revealed
      increasing body mass index (OR 1.1, P = .042) and RENAL score (OR 1.71, P = .002)
      as being independently associated with development of postoperative de novo
      estimated glomerular filtration rate <60. Multivariable analysis of the clamped
      subgroup demonstrated increasing body mass index (OR 1.12, P = .028), RENAL score
      (OR 1.56, P = .010), and ischemia time (OR 1.15, P = .042) as independent factors
      associated with de novo estimated glomerular filtration rate <60. CONCLUSION:
      Body mass index and RENAL score were factors predictive of development of de novo
      estimated glomerular filtration rate <60 after partial nephrectomy, with
      increasing warm ischemia time also being predictive in clamped partial
      nephrectomy patients. Further investigation and long-term functional data are
      requisite.

PMID- 22951009
TI  - Stock or stroke? Stock market movement and stroke incidence in Taiwan.
AB  - This paper investigates the impact of stock market movement on incidences of
      stroke utilizing population-based aggregate data in Taiwan. Using the daily data
      from the Taiwan Stock Exchange Capitalization Weighted Stock Index and from the
      National Health Insurance Research Database during 2001/1/1-2007/12/31, which
      consist of 2556 observations, we examine the effects of stock market on stroke
      incidence - the level effect and the daily change effects. In general, we find
      that both a low stock index level and a daily fall in the stock index are
      associated with greater incidences of stroke. We further partition the data on
      sex and age. The level effect is found to be significant for either gender, in
      the 45-64 and 65 >= age groups. In addition, two daily change effects are found
      to be significant for males and the elderly. Although stockholdings can increase
      wealth, they can also increase stroke incidence, thereby representing a cost to
      health.

PMID- 22951010
TI  - The case for addressing explosive weapons: conflict, violence and health.
AB  - In recent years, states and non-governmental organizations have expressed concern
      about the humanitarian consequences of the category of technologies labelled
      'explosive weapons', particularly in relation to their use in populated areas.
      This article seeks to outline the magnitude of these consequences as well as what
      can be done to reduce harms. In particular, it makes a case for how health
      approaches could help prevent the harms associated with this category of weapons.
      Attention is given to the types of evidence and argument that might be required
      to characterize explosive weapons. An overarching aim is to consider how
      alternative ways of understanding weapons and violence can create new
      opportunities for addressing harms from conflict.

PMID- 22951011
TI  - When you can't have the cake and eat it too: a study of medical doctors'
      priorities in complex choice situations.
AB  - Available literature provides little insight into medical doctors' prescription
      choices when they are required to make complex trade-offs between different
      concerns such as treatment effect, costs, and patient preferences simultaneously.
      This study investigates this issue. It is based on a Discrete Choice Experiment
      (DCE) conducted with 571 Norwegian doctors, where the DCE captures preferences
      for medications described along five dimensions important for both clinical
      decision-making and prioritisation in the health sector. Although effectiveness
      is the most important determinant of choice in our study, doctors also put
      considerable weight on patients' preferences and on avoiding high total costs.
      The probability of choosing a particular medication increases when doctors have a
      positive experience with the medication. GPs value high clinical effectiveness
      less than hospital consultants do. They are also less concerned with patient
      preferences. For both groups of doctors it turns out that they are willing to
      make difficult trade-offs between attributes they are often assumed not to be
      willing to compromise on, like effectiveness or patient preferences, and cost
      measures - given that they have proper information about these attributes.

PMID- 22951012
TI  - Postpartum emotional support: a qualitative study of women's and men's
      anticipated needs and preferred sources.
AB  - Australian health policy emphasises prevention, early intervention and improved
      pathways to treatment for perinatal mental disorders. Primary care is vital to
      achieving these aims. The aim of this study was to understand the anticipated
      needs and preferred sources of mental health information and support of men and
      women expecting their first baby. Nulliparous English-speaking expectant parents
      attending childbirth education programs in public and private hospitals
      participated in single sex small group discussions in late pregnancy. Discussions
      were audio-recorded, transcribed and analysed thematically using the group as the
      unit of analysis. Eight groups (22 women; 16 men) encompassing diverse
      socioeconomic circumstances were conducted. Analyses showed idealised fantasies
      consistently tempered with realistic expectations about adjustment to life with a
      baby. However, there were diverse and gendered views about whether primary care
      providers should discuss mental health with parents of infants and willingness to
      complete written questionnaires or be referred for specialist mental health care.
      Men regard primary family care as mother not father inclusive. Expectant parents
      readily anticipate realistic postnatal adjustment and need for emotional support.
      Increased provision of services that meet men's needs and public understanding
      and acceptance of Australian integrated models of primary postnatal mental health
      care are needed.

PMID- 22951013
TI  - Effect of cooled storage on quality and DNA integrity of Asian elephant (Elephas
      maximus) spermatozoa.
AB  - Artificial insemination (AI) is a potentially useful tool for breeding captive
      elephants because it facilitates efforts to minimise inbreeding. However, cooled
      storage of elephant semen markedly reduces fertility. This study compared the
      effects on semen-quality parameters, including sperm DNA fragmentation, of
      storing elephant semen at 4 degrees C or 15 degrees C in a commonly-used diluent
      (TEST) or a diluent developed to protect against sperm DNA damage (BullMax).
      Storing elephant semen for >24 h in either extender at either temperature
      resulted in decreases in sperm motility, viability, acrosome integrity and DNA
      integrity (P < 0.05); the decrease in motility was especially rapid. A subjective
      impression of circular sperm movement in TEST was confirmed by a higher
      curvilinear velocity and amplitude of lateral head displacement, but lower
      straight-line velocity and linearity than in BullMax. Initial percentages of
      spermatozoa with fragmented DNA (%SDF) did not differ between extenders or
      temperatures, but the rate of increase in %SDF during a 48-h incubation at 37
      degrees C was higher in TEST than in BullMax (P < 0.05). In conclusion, BullMax
      allows more linear movement and better preserves DNA stability of stored elephant
      spermatozoa than TEST. Sperm DNA stability during incubation at 37 degrees C is a
      promising, discriminative parameter for selecting semen storage conditions of
      bulls for elephant AI.

PMID- 22951014
TI  - Predictive role of plasma vascular endothelial growth factor for the effect of
      celecoxib in advanced non-small cell lung cancer treated with chemotherapy.
AB  - AIM OF THE STUDY: The primary purpose of this study is to investigate if
      pretreatment plasma levels of vascular endothelial growth factor (VEGF) are
      predictive of the effect of celecoxib on survival in advanced non-small cell lung
      cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to
      describe the course of plasma VEGF levels during and after treatment with
      cytotoxic chemotherapy combined with celecoxib or placebo. METHODS: In a
      previously published double-blind multicenter phase III trial, 316 patients with
      NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2
      were randomised to receive celecoxib 400mg b.i.d. or placebo in combination with
      two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks
      and planned duration of chemotherapy was four cycles. Celecoxib was given for a
      maximum of one year but was stopped earlier in case of disease progression or
      prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined
      at onset of treatment and at 6, 12 and 20 weeks. RESULTS: VEGF levels at start of
      treatment were obtained in 107 patients at four study sites. The median value was
      70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20
      weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an
      inverse relationship between initial plasma VEGF and the impact of celecoxib on
      survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in
      the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence
      interval (CI) 0.43-0.95], p=0.028). CONCLUSION: Low pretreatment plasma levels of
      VEGF appear to be predictive of a positive effect of celecoxib on survival.

PMID- 22951015
TI  - Prospective technical validation and assessment of intra-tumour heterogeneity of
      a low density array hypoxia gene profile in head and neck squamous cell
      carcinoma.
AB  - BACKGROUND AND PURPOSE: Tumour hypoxia is associated with a poor prognosis in
      head and neck squamous cell carcinoma (HNSCC), however there is no accepted
      method for assessing hypoxia clinically. We aimed to conduct a technical
      validation of a hypoxia gene expression signature using the TaqMan Low Density
      Array (TLDA) platform to investigate if this approach reliably identified hypoxic
      tumours. MATERIALS AND METHODS: Tumour samples (n=201) from 80 HNSCC patients
      were collected prospectively from two centres. Fifty-three patients received
      pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS)
      were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and
      customised TLDA cards. Assay performance was assessed as coefficient of variation
      (CoV). RESULTS: The assay was sensitive with linear reaction efficiencies across
      a 4 log(10) range of inputted cDNA (0.001-10 ng/MUl). Intra- (CoV=6.9%) and inter
      (CoV=2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was
      lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene
      measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell
      lines increased with decreasing pO(2). TLDA-HS correlated with Affymetrix U133
      Plus 2.0 microarray HS (p<0.01) and positive pimonidazole scores (p=0.005).
      CONCLUSIONS: Gene expression measurements of hypoxia using a 25-gene signature
      and TLDA cards are sensitive, reproducible and associated with lower intra-tumour
      heterogeneity than assaying individual genes or pimonidazole binding. The
      approach is suitable for further assessment of prognostic and predictive
      capability in clinical trial material.

PMID- 22951016
TI  - Cervical cancer screening and abnormalities among women in a residential drug
      rehabilitation program.
AB  - Women in a residential drug-rehabilitation program had lower rates of cervical
      screening attendance and higher rates ofdetected abnormalities than women
      attending a local Well Women's Clinic. As a result ofthis study we plan to
      include a more comprehensive sexual health history into routine women's health
      consultations.

PMID- 22951017
TI  - Tracheostomy teams reduce total tracheostomy time and increase speaking valve
      use: a systematic review and meta-analysis.
AB  - PURPOSE: Multidisciplinary tracheostomy teams have been implemented in acute
      hospitals over the past 10 years. This systematic review of the literature and
      meta-analysis aimed to assess the effect of tracheostomy teams on patient
      outcomes. MATERIALS AND METHODS: We conducted an electronic search of the
      literature in the following databases: MEDLINE, CINAHL, EMBASE, and AMED.
      Inclusion/exclusion criteria were applied, and included articles were assessed
      against quality criteria. Qualitative synthesis and meta-analysis were completed.
      RESULTS: Seven studies were included. The studies were all pre-post cohort
      designs of low-moderate quality. Meta-analysis showed that tracheostomy teams
      were associated with reductions in total tracheostomy time (4 studies; mean
      difference, 8 days; 95% confidence interval, 6-11; P < .01; I(2) = 0%) and
      hospital length of stay (LOS) (3 studies; mean difference, -14 days; 95%
      confidence interval, -39 to 9; P = .23; I(2) = 50%). Reductions in intensive care
      unit LOS (3 studies) and increases in speaking valve (3 studies) use were also
      reported with tracheostomy teams. CONCLUSION: There is low-quality evidence that
      multidisciplinary tracheostomy care contributes to a reduction in total
      tracheostomy time and increase speaking valve use for patients leading to
      improved quality of life. There is insufficient evidence to determine that
      multidisciplinary tracheostomy teams reduce hospital or intensive care unit LOS.

PMID- 22951018
TI  - Microparticles and acute renal dysfunction in septic patients.
AB  - PURPOSE: The role of microparticles (MPs) in the pathogenesis of sepsis is not
      completely elucidated. We aimed to assess changes in the number of MPs during
      severe sepsis to follow the effect of sepsis-related organ failures, particularly
      renal impairment, an independent mortality factor of sepsis. MATERIALS AND
      METHODS: Thirty-seven severe septic patients and 20 controls were enrolled.
      Patient status as well as organ failure-related laboratory markers was followed
      up to 5 consecutive days. Microparticles (annexin V+ events in MP size gate) of
      platelet (CD41, CD42a, and PAC1), monocyte (CD14), and myeloid cell line (CD13)
      origin were measured using flow cytometry. RESULTS: Significantly increased total
      MP and CD41-, CD42a-, and PAC1-positive particle numbers were found in septic
      patients compared with controls. Actual number of organ dysfunctions on sample
      collection showed no correlation with MP numbers. Septic patients with renal
      dysfunction showed an increase in total MP, CD41(+), and CD13(+) particle numbers
      on admission. Amounts of platelet-derived CD42a(+) particles from patients with
      sepsis-related renal injury correlated negatively with actual blood urea nitrogen
      and creatinine concentrations. CONCLUSION: The increased numbers of platelet
      derived MPs in severe septic patients emphasize the possible contribution of the
      hemostasis system in the development of sepsis-related renal impairments.

PMID- 22951019
TI  - Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a
      comparison between 2 citrate modalities and unfractionated heparin.
AB  - PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated
      continuous hemodiafiltration (CVVHDF) modalities and a heparin modality.
      MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and
      lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium
      containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium
      citrate with calcium-free low-bicarbonate buffered fluids
      (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering
      (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total
      bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h
      (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with
      Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in
      ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate
      groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in
      ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in
      ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The
      higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher
      blood flow used in this modality and the calcium-containing dialysate.
      CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate
      and citrate. The amount substantially differs between modalities despite a
      similar CVVHDF dose and is unacceptably high when using ACD with calcium
      containing lactate-buffered solutions and a higher blood flow. When calculating
      nutritional needs, we should account for the energy delivered by CVVHDF.

PMID- 22951021
TI  - New South Wales and Australian Capital Territory Researcher Development Program
      2005-07: modest investment, considerable outcomes.
AB  - This evaluation of the Researcher Development Program (RDP) in NSW and ACT aimed
      to determine whether the RDP was effective in assisting novice researchers to
      undertake primary health care research. In mid-2008, 47 participants of the NSW
      and ACT RDP during 2005-07 were invited to participate in a postal survey. The
      survey included questions regarding previous research training and experience,
      outcomes during and after participation in the program, and organisational
      aspects of the program. Follow-up interviews were conducted with selected
      participants. Interview questions covered time in the program, supervision,
      organisational support and placement outcomes. Thirty-seven participants
      responded to the survey and 23 (62%) participants took part in the semi
      structured interviews. Seventy-eight per cent of survey respondents felt that the
      RDP helped them move from novice to a more experienced researcher with effective
      supervision identified by participants as a key element in determining the
      success of the program. Many felt that time allocation was inadequate and 20%
      thought their capacity to maintain their workload was adversely affected by
      participating. Outcomes were considerable given the modest nature of the program.
      Notable outcomes were that most participants published their research and
      presented their research at a conference. Furthermore, one-fifth of survey
      respondents had enrolled in higher degrees. Several interviewees reported that
      their research led to changes in practice. Most respondents found the RDP
      valuable and considered that undertaking the program increased their research
      knowledge.

PMID- 22951020
TI  - Functional analysis of transcription factor binding sites in human promoters.
AB  - BACKGROUND: The binding of transcription factors to specific locations in the
      genome is integral to the orchestration of transcriptional regulation in cells.
      To characterize transcription factor binding site function on a large scale, we
      predicted and mutagenized 455 binding sites in human promoters. We carried out
      functional tests on these sites in four different immortalized human cell lines
      using transient transfections with a luciferase reporter assay, primarily for the
      transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1. RESULTS: In each
      cell line, between 36% and 49% of binding sites made a functional contribution to
      the promoter activity; the overall rate for observing function in any of the cell
      lines was 70%. Transcription factor binding resulted in transcriptional
      repression in more than a third of functional sites. When compared with predicted
      binding sites whose function was not experimentally verified, the functional
      binding sites had higher conservation and were located closer to transcriptional
      start sites (TSSs). Among functional sites, repressive sites tended to be located
      further from TSSs than were activating sites. Our data provide significant
      insight into the functional characteristics of YY1 binding sites, most notably
      the detection of distinct activating and repressing classes of YY1 binding sites.
      Repressing sites were located closer to, and often overlapped with, translational
      start sites and presented a distinctive variation on the canonical YY1 binding
      motif. CONCLUSIONS: The genomic properties that we found to associate with
      functional TF binding sites on promoters -- conservation, TSS proximity, motifs
      and their variations -- point the way to improved accuracy in future TFBS
      predictions.

PMID- 22951022
TI  - Solid bolt fixation of the medial column in Charcot midfoot arthropathy.
AB  - Charcot medial column and midfoot deformities are associated with rocker bottom
      foot, recurrent plantar ulceration, and consequent infection. The primary goal of
      surgical intervention is to realign and stabilize the plantar arch in a shoe
      able, plantigrade alignment. Different fixation devices, including screws,
      plates, and external fixators, can be used to stabilize the Charcot foot;
      however, each of these methods has substantial disadvantages. To assess the
      effectiveness of rigid, minimally invasive fixation of the medial column and
      midfoot, 8 cases of solid intramedullary bolt fixation for symptomatic Charcot
      neuroarthropathy were reviewed. The patients included 6 males (75%) and 2 females
      (25%), with a mean age of 63 (range 46 to 80) years. The Charcot foot deformity
      was caused by diabetic neuropathy in 7 cases (87.5%) and alcoholic neuropathy in
      1 (12.5%). The mean duration of postoperative follow-up period was 27 (range 12
      to 44) months. The mean radiographic correction of the lateral talar-first
      metatarsal angle was 15 degrees  (range 3 degrees  to 19 degrees ), and the mean
      radiographic correction of the dorsal midfoot dislocation was 9 (range -4 to 23)
      mm. The mean loss of correction of the lateral talar-first metatarsal angle and
      midfoot dislocation after surgery was 7 degrees  (range 0 degrees  to 26 degrees
      ) and 1 (range 0 to 7) mm, respectively. No bolt breakage was observed, and no
      cases of recurrent or residual ulceration occurred during the observation period.
      Bolt removal was performed in 3 cases (37.5%), 2 (25%) because of axial migration
      of the bolt into the ankle joint and 1 (12.5%) because of infection. The results
      of the present review suggest that a solid intramedullary bolt provides
      reasonable fixation for realignment of the medial column in cases of Charcot
      neuroarthropathy.

PMID- 22951023
TI  - [Influence of prenatal hospitalization on parental stressful experience in the
      case of a premature birth].
AB  - OBJECTIVES: To investigate the influence of prenatal hospitalization before a
      premature birth, on the parental stressful experience, parental symptoms of post
      traumatic stress and quality of parent-infant interaction during the
      hospitalization in neonatology. POPULATION AND METHODS:  POPULATION: 51 preterm
      infants born and 25 full term infants control. Four groups: controls, premature
      without prenatal hospitalization, premature with a short (<8 days) prenatal
      hospitalization and premature with a long (>= 8 days) prenatal hospitalization.
      INSTRUMENTS: the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:
      NICU, Miles et al., 1993 [14]) and the Perinatal PTSD Questionnaire (PPQ,
      Quinnell and Hynan, 1999 [16]). RESULTS: When prenatal hospitalization of the
      mother occurred, parents acknowledged increased stress induced by the
      environmental factors during the infant's hospitalization. Furthermore, mothers
      from the group with a short prenatal hospitalization presented significantly more
      symptoms of post-traumatic stress. Parents presenting more symptoms of post
      traumatic stress describe a significantly more difficult interaction with their
      infant in neonatology. CONCLUSION: This study highlights the necessity to deliver
      special care to women hospitalized shortly (<8 days) prior to the delivery of
      their premature baby. This group is at high risk of presenting post-traumatic
      stress symptoms, which could have a negative impact on the quality of parent
      infant interactions.

PMID- 22951024
TI  - Spindle assembly checkpoint regulation of chromosome segregation in mammalian
      oocytes.
AB  - The spindle assembly checkpoint (SAC) is a surveillance mechanism that monitors
      the quality of the spindle during division and blocks anaphase entry in the
      presence of anomalies that could result in erroneous segregation of the
      chromosomes. Because human aneuploidy is mainly linked to the erroneous
      segregation of genetic material in oocytes, the issue of the effectiveness of the
      SAC in female meiosis is especially important. The present review summarises our
      understanding of the SAC control of mammalian oocyte meiosis, including its
      possible impact on the incidence of embryonic aneuploidy. Owing to the
      peculiarities of cell cycle control in female meiosis, the integration of the SAC
      within such a specific environment results in several unusual situations, which
      are also discussed.

PMID- 22951025
TI  - Polymerization of ethyl methacrylate under the influence of ultrasound assisted a
      new multi-site phase-transfer catalyst system--a kinetic study.
AB  - The kinetics of multi-site phase-transfer catalyzed free radical polymerisation
      of ethyl methacrylate (EMA) using potassium peroxy disulphate (PDS) as a water
      soluble initiator and newly synthesized 1,4-dihexadecylpyrazine-1,4-diium
      dibromide as multi-site phase-transfer catalyst (MPTC) has been investigated in
      ethyl acetate/water two phase system at constant temperature 55 +/- 1  degrees C
      under nitrogen atmosphere and ultrasound irradiation conditions. The rate of
      polymerization increases with an increase in concentrations of EMA, PDS and MPTC.
      The order with respect to monomer, initiator and MPTC were found to be 1.03, 0.52
      and 0.53, respectively. Based on the observed results a suitable mechanism has
      been proposed to account for the experimental observations and its significance
      was discussed.

PMID- 22951026
TI  - Do frail older persons need more protein?

PMID- 22951027
TI  - Squamous cell carcinoma of the anal canal: a review of the aetiology,
      presentation, staging, prognosis and methods available for treatment.
AB  - Anal cancer is an uncommon malignancy, with the majority of cases comprised of
      squamous cell carcinomas. The increasing incidence of this disease reflects a
      rise in the transmission of the human papillomavirus, the causative organism of
      most tumours. Abdominoperineal resection (APR), once the primary mode of
      treatment, has been supplanted by sphincter-saving combination chemoradiation as
      the first-line therapy. However, surgeons continue to play a role in the
      multidisciplinary management of patients with anal cancer for diagnosis and post
      treatment surveillance. Sentinel node biopsy may identify patients with
      clinically and radiographically negative inguinal lymph nodes who will benefit
      from groin irradiation. In very select cases, the controversial means of local
      excision has been employed as primary treatment, often in conjunction with
      radiation and chemotherapy. The management of persistent or recurrent anal
      cancers following primary chemoradiation remains a concern, for which only
      salvage APR currently offers the possibility of a cure. The introduction of human
      papillomavirus vaccines presents the exciting potential for the eradication of
      the disease.

PMID- 22951028
TI  - A water-based training program that includes perturbation exercises improves
      speed of voluntary stepping in older adults: a randomized controlled cross-over
      trial.
AB  - This study evaluated the effects of a water exercise training program that
      includes perturbation exercises (WEP) to improve the speed of voluntary stepping
      reaction in older adults. Speed of voluntary stepping considered as an important
      skill to prevent a fall when balance is lost. In a single-blinded randomized
      controlled trial with a crossover design thirty-six independent old adults (64-88
      years old) were divided into two groups. Group A received WEP for the first 12
      weeks, followed by no intervention for the second 12 weeks. Group B did not
      receive intervention for the first 12 weeks and received WEP for the second 12
      weeks. Voluntary Step Execution Test and postural stability in upright standing
      (eyes open and closed conditions) were measured at baseline, 12 weeks, and 24
      weeks. A significant interaction effect between group and time was found for the
      step execution, due to improvement in initiation phase and swing phase durations
      in the WEP group. Also significant improvement in postural stability parameters
      in eyes open and closed conditions is noted. The present results indicate that
      the primary benefit of WEP that include perturbations to induce stepping, was a
      reduction in voluntary stepping times. The WEP generalized to a better control of
      balance in up-right standing.

PMID- 22951029
TI  - Corticospinal and intracortical excitability of the quadriceps in active older
      and younger healthy adults.
AB  - Age-related declines in neuromuscular function are well-documented, though the
      mechanisms underlying these deficits are unclear. Specific changes in
      corticospinal and intracortical neurophysiology may contribute, but have not been
      well studied, especially in lower extremity muscles. Furthermore, variations in
      physical activity levels may potentially confound the interpretation of
      neurophysiologic findings. Therefore, the purpose of this study was to quantify
      differences in transcranial magnetic stimulation (TMS) measures of corticospinal
      and intracortical excitability of the quadriceps between healthy, active older
      and younger adults. Twenty younger (age: 25.2 +/- 2.4 years; body mass index
      [BMI]: 22.1 +/- 3.0 kg/m(2); 11 males and 9 females) and twenty older (age: 67.7
      +/- 5.5 years; BMI: 26.8 +/- 3.8 kg/m(2); 11 males and 9 females) subjects who
      exercised regularly (at least 30 min, 3 times/week) completed testing. Motor
      evoked potentials (MEPs) were measured by superficial electromyographic
      recordings of the vastus lateralis (VL). Measures of corticospinal excitability
      using a double cone TMS coil included resting motor thresholds (RMT), resting
      recruitment curves (RRCs) and silent periods (SP). Intracortical excitability was
      measured using paired pulse paradigms for short interval intracortical inhibition
      (SICI) and intracortical facilitation (ICF). No statistically significant
      differences between older and younger adults were found for RMT, RRC slopes, SP,
      SICI or ICF measures (p>0.05). The physically active nature of the older adults
      included in this study may have contributed to the lack of differences in
      corticospinal and intracortical excitability since physical activity in older
      adults attenuates age-related declines in neuromuscular function.

PMID- 22951031
TI  - Highly sensitive and selective dopamine biosensor based on 3,4,9,10-perylene
      tetracarboxylic acid functionalized graphene sheets/multi-wall carbon
      nanotubes/ionic liquid composite film modified electrode.
AB  - A sensitive and selective electrochemical sensor for determination of dopamine
      (DA) was fabricated based on 3,4,9,10-perylene tetracarboxylic acid
      functionalized graphene sheets, multi-wall carbon nanotubes and ionic liquid
      modified glass carbon electrode and the properties of modified electrode were
      characterized by scanning electron microscopy, transmission electron microscope
      and electrochemical impedance spectroscopy. The modified electrode showed
      excellent electrocatalytic activity toward the oxidation of DA. Meanwhile, a
      possible reaction mechanism related to the oxidation of DA was proposed. The
      differential pulse voltammetry was used for the determination of DA in the
      presence of 500 MUM ascorbic acid and 330 MUM uric acid under the optimum
      conditions and a good linear relationship between peak current and the
      concentration of DA was obtained in the concentration range from 0.03 MUM to 3.82
      mM with a detection limit of 1.2*10(-9) M (S/N=3). Moreover, the proposed method
      was successfully applied to determine DA in real sample and satisfactory results
      were obtained. The results showed that the modified electrode exhibits an
      excellent catalytic activity, good sensitivity, reproducibility and long-term
      stability.

PMID- 22951030
TI  - The effect of third-party reporting on adoption of evidence-based mesalazine
      regimens in ulcerative colitis: an observational study.
AB  - BACKGROUND AND AIMS: The optimal mesalazine dosing strategy for ulcerative
      colitis (UC) continues to evolve. The current study aimed to explore whether
      documenting drug use could prompt changes in prescribing habits. METHODS: In a
      multicenter, prospective, observational study, outpatients with active or
      quiescent UC were enrolled if they were receiving, or were planned to receive,
      sustained release mesalazine microgranules (Pentasa). Clinical and prescribing
      data were collected at study entry, after 2 and 8 weeks. Physician-reported
      influences on prescribing decisions were recorded at study entry. RESULTS: 360
      patients were analyzed (203 active UC, 157 remission). Prior to study entry, the
      range of oral mesalazine doses was 0.50-6.00 g/day in active UC patients, and
      0.50-4.00 g/day for patients in remission. These changed to 1.50-5.00 g/day and
      1.00-4.00 g/day, respectively, at study entry with little change thereafter. Use
      of a single daily mesalazine dose increased from 16.7% to 58.0% of active cases
      during the study, and from 5.9% to 46.8% in remission cases. Gastroenterologists
      reported that their basis for prescription decision-making was most frequently
      medical experience (80.8%), followed by guidelines (67.2%), further education or
      colleagues' recommendations (50.0%) and current study results (20.0%).
      CONCLUSION: In this analysis of mesalazine dosing in routine clinical practice,
      there was an improvement in adherence to European Crohn's and Colitis
      Organisation (ECCO) guidelines and in use of once-daily dosing, consistent with
      recent trial results, following documentation of dosing regimens. Written
      reporting of drug dosing schedules should be considered fundamental for chronic,
      complex diseases such as UC.

PMID- 22951032
TI  - Thirty-day outcomes support implementation of a surgical safety checklist.
AB  - BACKGROUND: Thirty-day postoperative complications from unintended harm adversely
      affect patients and their families and increase institutional health care costs.
      A surgical checklist is an inexpensive tool that will facilitate effective
      communication and teamwork. Surgical team training has demonstrated the
      opportunity for stakeholders to professionally engage one another through
      leveling of the authority gradient to prevent patient harm. The American College
      of Surgeons National Surgical Quality Improvement Program database is an outcomes
      reporting tool capable of validating the use of surgical checklists. STUDY
      DESIGN: Three 60-minute team training sessions were conducted and participants
      were oriented to the use of a comprehensive surgical checklist. The surgical team
      used the checklist for high-risk procedures selected from those analyzed for the
      American College of Surgeons National Surgical Quality Improvement Program.
      Trained observers assessed the checklist completion and collected data about
      perioperative communication and safety-compromising events. RESULTS: Data from
      the American College of Surgeons National Surgical Quality Improvement Program
      were compared for 2,079 historical control cases, 246 cases without checklist
      use, and 73 cases with checklist use. Overall completion of the checklist
      sections was 97.26%. Comparison of 30-day morbidity demonstrated a statistically
      significant (p = 0.000) reduction in overall adverse event rates from 23.60% for
      historical control cases and 15.90% in cases with only team training, to 8.20% in
      cases with checklist use. CONCLUSIONS: Use of a comprehensive surgical safety
      checklist and implementation of a structured team training curriculum produced a
      statistically significant decrease in 30-day morbidity. Adoption of a
      comprehensive checklist is feasible with team training intervention and can
      produce measurable improvements in patient outcomes.

PMID- 22951033
TI  - Deciding laparoscopic approaches for wedge resection in gastric submucosal
      tumors: a suggestive flow chart using three major determinants.
AB  - BACKGROUND: The aim of this study was to determine the optimal laparoscopic
      approach for wedge resection of gastric submucosal tumors (SMTs) based on tumor
      characteristics. STUDY DESIGN: Between March 2008 and June 2010, 57 patients
      underwent laparoscopic wedge resection for suspected gastric SMT. Of these 57
      patients, 40 underwent exogastric wedge resection (EWR), with the remaining
      undergoing transgastric wedge resection (TWR). RESULTS: Fifty-seven consecutive
      patients undergoing surgical resection of gastric SMT were reviewed, with 40 and
      17 tumors treated with EWR and TWR, respectively. The average tumor size was
      significantly greater in the EWR group (p = 0.004). A circular tumor location was
      a decisive factor for selecting the laparoscopic approach (p = 0.011). Tumors
      presenting with exophytic growths were predominantly found in the EWR group, and
      those with endophytic growth were dominant in the TWR group (p < 0.001). A
      multivariate analysis to determine the independent factors influencing the choice
      for EWR or TWR revealed that tumor size (95% CI, 1.1 to 20.0; p = 0.033) and
      circular location of tumor (95% CI, 1.4 to 106.9; p = 0.021) were statistically
      significant factors. CONCLUSIONS: These data suggest a strategy for selection of
      appropriate laparoscopic wedge resection strategies based on tumor
      characteristics. This decision is affected by tumor size, location, and growth
      pattern.

PMID- 22951034
TI  - Conversion of the gastric LAP-BAND port to low-profile access: an adjunctive
      technique during abdominoplasty in the bariatric patient.

PMID- 22951035
TI  - Being a botanist and a gardener: using diagnostic frameworks in general practice
      patients with medically unexplained symptoms.
AB  - Patients with multiple medically unexplained symptoms commonly seek treatment in
      primary care. Many of these patients seem to have a psychological 'core' to their
      illness that affects the way they experience, conceptualise and communicate their
      distress. There is considerable debate around diagnosis for this group of
      patients. Existing diagnoses include somatoform disorders in psychiatry and
      functional disorders in the medical specialties. Some clinicians use the term
      'heartsink' patients, which reflects the interpersonal frustration inherent in
      some therapeutic relationships. A good diagnosis should be clinically useful,
      helping clinicians and patients understand and manage illness. Diagnosis should
      also provide a reliable classification for research and evidence-based treatment.
      The allegory of the botanist and the gardener has been used to describe
      diagnosis. For the botanist, a good diagnosis produces a taxonomy that is
      rigorous and reliable. For the gardener, it informs the way a garden is described
      and understood in a specific context. Clinicians need both: a 'botanical' type of
      classification to bring rigour to research and therapy, and clinical 'gardening',
      which allows for multiple perspectives and diagnostic frameworks. Clinical
      reasoning is a form of research with therapeutic intent. Botany and gardening
      represent a mixed-methods approach that can enrich diagnosis. The challenge is to
      integrate multiple perspectives in clinically helpful ways that help us retain
      both richness and rigour. 

PMID- 22951036
TI  - ROCK inhibitor Y-27632 enhances the survivability of dissociated buffalo (Bubalus
      bubalis) embryonic stem cell-like cells.
AB  - This study investigated the effects of supplementation of culture medium with 10
      MUM Y-27632, a specific inhibitor of Rho kinase activity, for 6 days on self
      renewal of buffalo embryonic stem (ES) cell-like cells at Passage 50-80. Y-27632
      increased mean colony area (P<0.05) although it did not improve their survival.
      It decreased OCT4 expression (P<0.05), increased NANOG expression (P<0.05), but
      had no effect on SOX2 expression. It also increased expression of anti-apoptotic
      gene BCL-2 (P<0.05) and decreased that of pro-apoptotic genes BAX and BID
      (P<0.05). It increased plating efficiency of single-cell suspensions of ES cells
      (P<0.05). Following vitrification, the presence of Y-27632 in the vitrification
      solution or thawing medium or both did not improve ES cell colony survival.
      However, following seeding of clumps of ES cells transfected with pAcGFP1N1
      carrying green fluorescent protein (GFP), Y-27632 increased colony formation rate
      (P<0.01). ES cell colonies that formed in all Y-27632-supplemented groups were
      confirmed for expression of pluripotency markers alkaline phosphatase, SSEA-4 and
      TRA-1-60, and for their ability to generate embryoid bodies containing cells that
      expressed markers of ectoderm, mesoderm and endoderm. In conclusion, Y-27632
      improves survival of buffalo ES cells under unfavourable conditions such as
      enzymatic dissociation to single cells or antibiotic-assisted selection after
      transfection, without compromising their pluripotency.

PMID- 22951038
TI  - Grip and pinch capability assessment system for children.
AB  - The grip movement is essential for performing daily activities. However, the
      assessment of this movement is currently made subjectively, due to the lack of
      appropriate quantification equipment. The objective of this study was to develop,
      validate and test a virtual environment controlled by five trigger devices used
      to analyse cylindrical, spherical and hook grips as well as tip-to-tip pinch and
      pulp-to-side movements. Sensors and electronic circuits that detect the correct
      grip, the threshold of grip strength and the range of motion were inserted into
      the devices. To validate this system, tests were conducted with 20 children while
      being evaluated by three physical therapists, all specialists in neurology. The
      results from the evaluators and the system agreed to an extent of 86.6%.
      Following validation, the system was used by 35 children with no motor impairment
      and by 10 children with mild motor abnormalities in an upper limb; these
      assessments provided efficient and reliable results. The developments presented
      in this study may help to assess grip and pinch movements and facilitate the
      choice of strategies in therapeutic processes.

PMID- 22951037
TI  - The GENCODE pseudogene resource.
AB  - BACKGROUND: Pseudogenes have long been considered as nonfunctional genomic
      sequences. However, recent evidence suggests that many of them might have some
      form of biological activity, and the possibility of functionality has increased
      interest in their accurate annotation and integration with functional genomics
      data. RESULTS: As part of the GENCODE annotation of the human genome, we present
      the first genome-wide pseudogene assignment for protein-coding genes, based on
      both large-scale manual annotation and in silico pipelines. A key aspect of this
      coupled approach is that it allows us to identify pseudogenes in an unbiased
      fashion as well as untangle complex events through manual evaluation. We
      integrate the pseudogene annotations with the extensive ENCODE functional
      genomics information. In particular, we determine the expression level,
      transcription-factor and RNA polymerase II binding, and chromatin marks
      associated with each pseudogene. Based on their distribution, we develop simple
      statistical models for each type of activity, which we validate with large-scale
      RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and
      variation data from primate alignments and the 1000 Genomes project, producing
      lists of pseudogenes potentially under selection. CONCLUSIONS: At one extreme,
      some pseudogenes possess conventional characteristics of functionality; these may
      represent genes that have recently died. On the other hand, we find interesting
      patterns of partial activity, which may suggest that dead genes are being
      resurrected as functioning non-coding RNAs. The activity data of each pseudogene
      are stored in an associated resource, psiDR, which will be useful for the initial
      identification of potentially functional pseudogenes.

PMID- 22951039
TI  - Evaluation of a minimally invasive renal cooling device using heat transfer
      analysis and an in vivo porcine model.
AB  - Partial nephrectomy is the gold standard treatment for renal cell carcinoma. This
      procedure requires temporary occlusion of the renal artery, which can cause
      irreversible damage due to warm ischemia after 30 min. Open surgical procedures
      use crushed ice to induce a mild hypothermia of 20 degrees C in the kidney, which
      can increase allowable ischemia time up to 2.5 h. The Kidney Cooler device was
      developed previously by the authors to achieve renal cooling using a minimally
      invasive approach. In the present study an analytical model of kidney cooling in
      situ was developed using heat transfer equations to determine the effect of
      kidney thickness on cooling time. In vivo porcine testing was conducted to
      evaluate the cooling performance of this device and to identify opportunities for
      improved surgical handling. Renal temperature was measured continuously at 6
      points using probes placed orthogonally to each other within the kidney. Results
      showed that the device can cool the core of the kidney to 20 degrees C in 10-20
      min. Design enhancements were made based on surgeon feedback; it was determined
      that the addition of an insulating air layer below the device increased
      difficulty of positioning the device around the kidney and did not significantly
      enhance cooling performance. The Kidney Cooler has been shown to effectively
      induce mild renal hypothermia of 20 degrees C in an in vivo porcine model.

PMID- 22951040
TI  - Phenolic constituents from the rhizomes of Acorus gramineus and their biological
      evaluation on antitumor and anti-inflammatory activities.
AB  - On the search for anti-cancer compounds from natural Korean medicinal sources, a
      bioassay-guided fractionation and chemical investigation of the MeOH extract from
      the rhizomes of Acorus gramineus resulted in the isolation and identification of
      thirteen phenolic derivatives (1-13) including two new 8-O-4'-neolignans, named
      surinamensinols A (1) and B (2) and a new phenolic compound, named acoramol (9).
      The structures of these new compounds were elucidated on the basis of 1D and 2D
      NMR spectroscopic data analyses as well as circular dichroism (CD) spectroscopy
      studies. The cytotoxic activities of the isolates (1-13) were evaluated by
      determining their inhibitory effects on human tumor cell lines. The new 8-O-4'
      neolignans, compounds 1 and 2, showed moderate antiproliferative activities
      against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC(50) values in the
      range of 4.17-26.18MUM. On the basis of the expanded understanding that
      inflammation is a crucial cause of tumor progression, anti-inflammatory
      activities of these compounds were determined by measuring nitric oxide (NO)
      levels in the medium using murine microglia BV-2 cells. Compounds 1, 2, 4, 7 and
      10 inhibited NO production in BV-2 stimulated by lipopolysaccharide with IC(50)
      values of 8.17-18.73MUM via NO scavenging, inhibition of iNOS activity, and/or
      suppression of iNOS expression.

PMID- 22951041
TI  - Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan
      replacement with alternative amino acids.
AB  - Daptomycin was shown to interact in vitro with pulmonary surfactant leading to
      reduction of its antibacterial activity. We report herein the preparation and
      anti-staphylococcal activity of a series of daptomycin analogs with reduced
      pulmonary surfactant interaction by replacing tryptophan with various amino
      acids.

PMID- 22951043
TI  - The sigma(1) receptor antagonist S1RA is a promising candidate for the treatment
      of neurogenic pain.

PMID- 22951042
TI  - [Laparoscopic drainage of a pancreatic pseudocyst: a case report].
AB  - Pancreatic pseudocysts are defined as homogeneous pancreatic or peripancreatic
      collections that are not associated with necrotic tissue and are surrounded by
      granulated or fibrous tissue with no epithelium. Management has been classified
      as surgical (conventional and laparoscopic) and nonsurgical (endoscopic and
      radiologic). The aim of this report is to describe our initial experience in the
      management of a pancreatic pseudocyst by means of laparoscopic posterior cyst
      gastrostomy anastomosis, performed at the Pancreas Clinic of the Hospital General
      "Dr. Manuel Gea Gonzalez" in Mexico City. New techniques and instrumentation have
      contributed to the relatively recent development of laparoscopic pancreatic
      surgery. Our technique has practical advantages that have been confirmed by other
      authors, such as simple hemostasis, a wide viewing angle enabling adequate
      necrosectomy, anastomosis that does not require the use of staples, and the
      possibility of resolving other associated intra-abdominal pathologies, as in this
      case.

PMID- 22951044
TI  - From state care to self-care: cancer screening behaviours among Russian-speaking
      Australian women.
AB  - In this article, we report on a small qualitative scale study with immigrant
      Russian-speaking Australian women, carers of dependent family members. Drawing on
      in-depth interviews, we explore women's health-related behaviours, in particular
      their participation in breast and cervical cancer screening. Differences in
      preventive health care policies in country of origin and Australia explain their
      poor participation in cancer screening. Our participants had grown up in the
      former Soviet Union, where health checks were compulsory but where advice about
      frequency and timing was the responsibility of doctors. Following migration,
      women continued to believe that the responsibility for checks was their doctor's,
      and they maintained that, compared with their experience of preventive medicine
      in the former Soviet Union, Australian practice was poor. Women argued that if
      reproductive health screening were important in cancer prevention, then health
      care providers would take a lead role to ensure that all women participated. Data
      suggest how women's participation in screening may be improved. 

PMID- 22951045
TI  - Role of the Chronic Dental Disease Scheme in Enhanced Primary Care: allied health
      or allied outlier?
AB  - This study aims to provide a comparative analysis of the Chronic Dental Disease
      Scheme (CDSS) and the Allied Health Profession (AHP) program as they related to
      the greater Enhanced Primary Care Scheme introduced by the Australian Government
      to manage patients with chronic and complex diseases. A retrospective analysis of
      data pertaining to Medicare items related to dentistry and the allied health
      professions were extracted from the Medicare Benefits Schedule database online,
      and formed the basis of this study. The highest proportion of services was
      provided in the state of New South Wales. There appears to be synergy in the
      utilisation of services with jurisdictions either overutilising or underutilising
      services. Costs to the Enhanced Primary Care Scheme under the CDSS model (fee for
      service) were up to 40 times more expensive compared with the AHP model (fee per
      visit). Costs and treatment associated with the CDSS experienced an increase of
      13350% during the period 2007-08, coincident with an increase in subsidization.
      Reconstructive dentistry accounted for the majority of the increase. Gender
      disparities in dentistry were less distinct when compared with AHPs and were
      postulated to be due to males presenting with conditions that were more
      progressive requiring more invasive treatment. A comparative analysis indicates
      significant differences in costs, nature of treatment and the manner of
      remuneration between dentistry and the AHPs. A fee for service schedule as
      evidenced by the CDSS is dependent on the degree of financial incentive as
      indicated by patterns in utilisation over time. The amount of treatment
      considered necessary may be influenced by the level of subsidy with treatment
      that may not reflect disease management. The AHP model, which is based around a
      fee for visit schedule, is not without its deficiencies but has not experienced
      significant rises in cost compared with the CDSS.

PMID- 22951046
TI  - Anal sex practices in heterosexual and male homosexual populations: a review of
      population-based data.
AB  - Anal sex is known to be an important risk factor for anal cancer. Yet compared
      with vaginal intercourse, little is known about anal sex practices in either
      heterosexual or male homosexual populations. Of the data that are available, it
      appears a significant and increasing minority of heterosexuals have ever
      practised anal intercourse. Among homosexual men, most, but not all, report anal
      sex, with large proportions of men engaging in both insertive and receptive anal
      intercourse. The most significant finding of the review was the dearth of
      population-based data, particularly relating to homosexual men.

PMID- 22951047
TI  - Relationship between arm morbidity and patient-reported outcomes following
      surgery in women with node-negative breast cancer: NSABP protocol B-32.
AB  - BACKGROUND: The impact of arm morbidity following breast cancer surgery on
      patient-observed changes in daily functioning and health-related quality of life
      (HRQoL) has not been well-studied. OBJECTIVE: To examine the association of
      objective measures such as range of motion (ROM) and lymphedema, with patient
      reported outcomes (PROs) in the arm and breast, upper extremity function,
      activities, and HRQoL. METHODS: The National Surgical Adjuvant Breast and Bowel
      Project Protocol B-32 was a randomized trial comparing sentinel node resection
      (SNR) with axillary dissection (AD) in women with node-negative breast cancer.
      ROM and arm volume were measured objectively. PROs included symptoms; arm
      function; limitations in social, recreational, occupational, and other regular
      activities; and a global index of HRQoL. Statistical methods included cross
      tabulations and multivariable linear regression models. RESULTS: In all, 744
      women provided at least 1 postsurgery assessment. About one-third of the patients
      experienced arm mobility restrictions. A similar number of patients avoided the
      use of the arm 6 months after surgery. Limitations in work and other regular
      activities were reported by about a quarter of the patients. In this
      multivariable analysis, arm mobility and sensory neuropathy were predictors of
      patient-reported arm function and overall HRQoL. Predictors for activity
      limitations also included side of surgery (dominant vs nondominant). Edema was
      not significant after adjustment for sensory neuropathy and ROM. LIMITATIONS: Arm
      mobility and edema were measured simultaneously only once during the follow-up (6
      months). CONCLUSION: Clinical measures of sensory neuropathy and restrictions in
      arm mobility following breast cancer surgery are associated with self-reported
      limitations in activity and reductions in overall HRQoL.

PMID- 22951048
TI  - Avoiding harmful palliative chemotherapy treatment in the end of life:
      development of a brief patient-completed questionnaire for routine assessment of
      performance status.
AB  - BACKGROUND: Earlier studies have shown that up to 43% of patients with incurable
      cancer are treated with palliative chemotherapy in the last month of their lives.
      Although pretreatment blood tests are acceptable, the patient's general condition
      may not permit further palliative chemotherapy treatment (PCT). Presently, there
      is no patient self-assessment tool available to monitor performance status during
      PCT. OBJECTIVES: To describe the development process of the Performance Status in
      Palliative Chemotherapy (PSPC) questionnaire, and the testing of its psychometric
      properties. METHODS: The questionnaire was developed by the authors based on the
      Eastern Cooperative Oncology Group Performance Status Rating (ECOG PSR) scale as
      well as their clinical experience with PCT. Adult patients who were diagnosed
      with epithelial cancers (n = 118) were enrolled to test the PSPC questionnaire
      for reliability, sensitivity for change, and validity. RESULTS: After stepwise
      modifications of the PSPC questionnaire, psychometric tests revealed acceptable
      values for reliability (via a test-retest method), sensitivity for change (via a
      comparison of patients with progressive disease over time), and validity (via a
      comparison of the PSPC vs the Edmonton Symptom Assessment System [ESAS]).
      LIMITATIONS: At this stage of questionnaire development, we are unable to
      conclude whether the PSPC is superior to the conventional ECOG PSR in the
      evaluation of performance status and the prediction of chemotherapy response.
      CONCLUSION: Psychometric tests suggest that the PSPC questionnaire may be a
      useful patient-completed tool in the late stages of cancer disease to routinely
      monitor performance status in palliative chemotherapy treatments so as to
      minimize the risk of inflicting more harm than good.

PMID- 22951049
TI  - Persistence of an immunoreactive MUC1 protein at the feto-maternal interface
      throughout pregnancy in the mare.
AB  - A polyclonal human mucin-1 (MUC1) antibody was used to stain
      immunohistochemically for the presence of MUC1 on the endometrium and fetal
      membranes in mares between 20 and 309 days of gestation. Western blot analysis
      demonstrated the presence of a protein equivalent in size to a human MUC1
      isoform, MUC1/Y, in equine endometrium, allantochorion and amnion. At all stages
      of gestation examined immunoreactivity to the MUC1 antibody was detected on the
      apical surface of the lumenal epithelium of the endometrium and the epithelium
      lining the mouths and apical regions of the endometrial glands. Furthermore, it
      persisted unchanged on the surface of the lumenal epithelium lying beneath the
      highly-invasive chorionic girdle component of the trophoblast before, during and
      after development of the endometrial cups. The MUC1 immunoreactive protein was
      also present on the trophoblast and other components of the fetal membranes
      during the post-fixation, pre-attachment period of gestation (20-40 days) and it
      persisted on the apical surface of the non-invasive trophoblast of the
      allantochorion before, during and after attachment, microvillous interdigitation
      and development of the microcotyledonary epitheliochorial placenta. Hence, the
      delayed placentation response in mares appears to occur independently of the
      persistence of an immunoreactive MUC1 protein at the feto-maternal interface.

PMID- 22951050
TI  - The rat oocyte synthesises melatonin.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine originally identified
      in the pineal gland, where it is synthesised enzymatically from serotonin (5
      hydroxytryptamine) by the sequential action of arylalkylamine N-acetyltransferase
      (AANAT) and acetylserotonin O-methyltransferase (ASMT; also known as
      hydroxyindole O-methyltransferase). Melatonin directly affects ovarian functions
      and previous studies have suggested that melatonin is synthesised in the ovary.
      In the present study, we examined whether AANAT and ASMT are expressed in the
      adult rat ovary. Reverse transcription-polymerase chain reaction analyses
      demonstrated that both AANAT and ASMT mRNAs are expressed in the ovary. Western
      blotting for AANAT protein showed that the ovary, like the pineal gland, contains
      this enzymatic protein with a molecular mass of 24kDa. Immunohistochemistry
      revealed that the AANAT protein is localised to the oocyte, corpus luteum and
      medulla, including mast cells. AANAT protein was found in oocytes at all stages
      of follicular development, and its levels in oocytes increased progressively
      throughout follicular development. Furthermore, isolated oocytes metabolised
      exogenous serotonin to melatonin. These findings demonstrate that melatonin is
      synthesised from serotonin in oocytes. Melatonin synthesised in the oocyte may be
      implicated in its own growth or maturation, for example, by acting as a
      calmodulin antagonist or an antioxidant.

PMID- 22951051
TI  - Essential genes as antimicrobial targets and cornerstones of synthetic biology.
AB  - Essential genes are absolutely required for the survival of any living entity.
      Investigation of essential genes is therefore expected to advance tremendously
      our understanding of the universal principles of life. Determination of a minimal
      set of essential genes needed to sustain life also plays an important role in the
      emerging field of synthetic biology, whose goals include creation of a
      stringently controlled minimal cell with predesigned phenotypic traits. In
      addition, due to their indispensability for survival of bacteria, genes encoding
      essential cellular functions have great potential in medicine as promising
      targets for the development of novel antimicrobials. Here, we review recent
      advances in the investigation of essential genes, with emphasis on the practical
      applications in medicine and synthetic biology.

PMID- 22951052
TI  - Post-traumatic bone and/or joint limb infections due to Clostridium spp.
AB  - BACKGROUND: Clostridium spp. are saprophytic Gram-positive bacteria found in soil
      and capable of generating endospores. Spore germination occurs when environmental
      conditions are favorable. Clostridium spp. can cause infections of compound
      fractures and deep wounds contaminated from soil micro-organisms. HYPOTHESIS:
      Clostridium spp. infections of traffic-related injuries are particularly severe
      events whose outcome is uncertain even with aggressive medical and surgical
      treatment. MATERIALS AND METHODS: We retrospectively reviewed 12 patients (median
      age, 45 years) with Clostridium spp. bone and/or joint infections complicating
      compound limb fractures with soil contamination and extensive soft-tissue damage.
      Prophylactic amoxicillin-clavulanic acid therapy was administred, followed by
      emergency surgical wound debridment and lavage. Fracture fixation was performed
      immediately in nine patients (external in four and internal in five) or at a
      later time on three patients. The immediate outcome was unfavourable in all 12
      cases, requiring early reoperation after a median of 10 days (range, 5-25 days).
      RESULTS: Median time to Clostridium strain identification was 14.5 days (range, 5
      160). All infections were polymicrobial. Surgical wound excision, hardware
      removal (in four cases), and antibiotic therapy produced a favourable outcome in
      one patient, with no recurrence after 2 years of follow-up; the outcome was
      unfavourable in 11 cases, with delayed fracture union, septic non-union, impaired
      healing, and/or chronic sinus tract drainage. Several second-line treatments were
      used in these 11 patients: intramedullary nailing without bone grafting in four
      patients, with three failures; decortication and grafting in two patients, with
      failure in both; nailing with decortication in one patient, who had a good
      outcome; and the induced membrane procedure described by Masquelet in four
      patients, all of whom had good outcomes. After a median follow-up of 24 months
      (range, 18-53 months), the bone infection had subsided in eight patients. The
      remaining four patients had septic non-union. DISCUSSION: Clostridium spp.
      infections are particularly severe. The diagnosis is delayed and identification
      of the organism is challenging. The treatment is difficult and results in
      unfavorable outcomes in one-third of cases. The identification of Clostridium in
      specimens from an osteoarticular infection indicates a need for extremely
      extensive and aggressive surgical resection, as spore resistance may impair the
      in vivo efficacy of antimicrobial agents. LEVEL OF EVIDENCE: IV (retrospective
      cohort study).

PMID- 22951053
TI  - Painful patellofemoral instability secondary to peroperative patellar fracture
      during bone-patellar tendon-bone autograft harvesting for anterior cruciate
      ligament reconstruction.
AB  - Reconstructive surgery of the anterior cruciate ligament (ACL) of the knee in
      young active patients is a routine procedure, but with certain risks that need to
      be taken into account. Peroperative patellar fracture after bone-patellar tendon
      bone autograft harvesting is a rare complication, which can significantly impair
      the functional outcome of ACL single-bundle reconstruction. We report the case of
      a patient presenting with disabling patellofemoral syndrome 3 years after
      arthroscopic ACL reconstruction by bone-tendon-bone autograft, revealing
      unnoticed mal-union of a iatrogenic sagittal patellar fracture. Patellar
      osteotomy corrected this painful iatrogenic patellar instability.

PMID- 22951054
TI  - Scarf osteotomy versus metatarsophalangeal arthrodesis in forefoot first ray
      disorders: comparison of functional outcomes.
AB  - INTRODUCTION: Scarf osteotomies of the first metatarsal and metatarsophalangeal
      arthrodesis are the two most frequent surgical forefoot reconstructive
      procedures. HYPOTHESIS: We compared functional results of isolated arthrodesis of
      the first metatarsophalangeal joint with an isolated Scarf osteotomy of the first
      metatarsal. MATERIALS AND METHODS: This was a retrospective, observational,
      continuous study of patients operated between 1993 and 2008. After patients who
      had undergone a procedure on the lateral rays, extremely elderly patients, lost
      to follow-up patients and those with incomplete questionnaires had been excluded,
      there remained two comparable groups of 25 patients. Mean age was 60 in the
      arthrodesis group [41-70] and 59.8 in the Scarf group [47-71]. The Scarf group
      included 25 hallux valgus (100%) compared to 16 hallux valgus (64%) and nine
      hallux rigidus (36%) in the arthrodesis group. Complications were recorded.
      Evaluation of functional results was based on the most recent functional or
      quality of life scores (AOFAS, FFI, FAAM, SF 36) and a questionnaire on physical
      and athletic ability. RESULTS: There was no significant difference in the rate of
      complications between the two groups. There was no difference in pain according
      to the AOFAS score with 35.6/40 (+/- 6.5) in the Scarf group and 34.5 (+/- 5.9)
      in the arthrodesis group. Global satisfaction was also similar between the Scarf
      and arthrodesis groups: 91.4% and 90% of very satisfied or satisfied patients,
      respectively. The FFI score was higher in the Scarf group than in the arthrodesis
      group: 8.6 (+/- 20.1) and 19.8 (+/- 17.7) respectively. Functional results were
      better in the Scarf group than in the arthrodesis group with a FAAM Daily
      Activity score of 80.2 (+/- 12.1) compared to 68 (+/- 7.2), a FAAM Sports
      Activity score of 29.7 (+/- 6.7) compared to 25.2 (+/- 7.6) and a FAAM Global
      Function score of 94% (+/- 10.8) compared to 87% (+/- 15.7), respectively. The
      Global SF36 score was higher in the Scarf group than in the arthrodesis group:
      70.9% (+/- 14.1) and 62.3% (+/- 20.6) respectively, which was due to a higher
      Mental Health score in the Scarf group: 68.7% (+/- 14.2) and 60.4% (+/- 19.3)
      respectively. In the area of sports activities the Scarf group practiced more
      hiking than the arthrodesis group (74% versus 42% respectively). There was no
      difference for other activities. DISCUSSION AND CONCLUSION: This study provides
      detailed information on the level of physical and sports activities that are
      practiced following these procedures, so that the patient can be better informed.

PMID- 22951055
TI  - Specificity and responsiveness of patient-reported and clinician-rated outcome
      measures in the context of elbow surgery, comparing patients with and without
      rheumatoid arthritis.
AB  - OBJECTIVES: To examine and contrast the ability of patient-reported and clinician
      rated measures, reflecting different levels of specificity, to detect differences
      in outcomes between patients with and without rheumatoid arthritis (RA), at 6
      months following elbow surgery. METHODS: One hundred and four consecutive
      patients/elbows self-completed the Oxford Elbow Score (OES), Disabilities of the
      Arm, Shoulder and Hand (DASH) and SF-36 general health questionnaires prior to
      elbow surgery. A surgeon assessed the standard Mayo Elbow Performance Score
      (MEPS) and recorded patients' diagnoses. Assessments were repeated 6 months
      following surgery in an outpatient clinic. Patients also completed pain
      "transition" and global satisfaction items. Patients who did not attend completed
      their assessment by post. RESULTS: Twenty-three (22%) patients had RA. These
      patients were more likely than other patients to have bilateral elbow problems
      and to have total elbow replacement (85.7% versus 10.5% P<0.001). Patients with
      RA had more severe preoperative elbow-specific scores, and experienced a large
      and significantly greater amount of change in elbow function, as measured by the
      OES function (P=0.002) and pain scales (P=0.013). The surgeon-assessed elbow
      specific MEPS score also detected a large and significant difference between the
      two groups (P<0.001). However, these differences were not detected by the upper
      limb specific DASH, by any SF-36 general health dimensions, or by transition or
      satisfaction items. CONCLUSIONS: The OES performed well in assessing surgical
      outcomes in patients with RA. Neither the upper limb specific DASH nor the SF-36
      is specific or responsive enough to warrant its exclusive use as an outcome
      measure for elbow surgery. LEVEL OF EVIDENCE: Level II (prospective non
      randomised study).

PMID- 22951056
TI  - Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins
      characterizes acute and chronic atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common disease with an increasing
      prevalence. The primary pathogenesis of the disease is still elusive, resulting
      in the lack of specific treatments. AD is currently considered a biphasic
      disease, with T(H)2 predominating in acute disease and a switch to T(H)1
      characterizing chronic disease. Elucidation of the molecular factors that
      participate in the onset of new lesions and maintenance of chronic disease is
      critical for the development of targeted therapeutics. OBJECTIVES: We sought to
      characterize the mechanisms underlying the onset and maintenance of AD. METHODS:
      We investigated intrapersonal sets of transcriptomes from nonlesional skin and
      acute and chronic lesions of 10 patients with AD through genomic, molecular, and
      cellular profiling. RESULTS: Our study associated the onset of acute lesions with
      a striking increase in a subset of terminal differentiation proteins,
      specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was
      also associated with significant increases in gene expression levels of major
      T(H)22 and T(H)2 cytokines and smaller increases in IL-17 levels. A lesser
      induction of T(H)1-associated genes was detected in acute disease, although some
      were significantly upregulated in chronic disease. Further significant
      intensification of major T(H)22 and T(H)2 cytokines was observed between acute
      and chronic lesions. CONCLUSIONS: Our data identified increased S100A7, S100A8,
      and S100A9 gene expression with AD initiation and concomitant activation of T(H)2
      and T(H)22 cytokines. Our findings support a model of progressive activation of
      T(H)2 and T(H)22 immune axes from the acute to chronic phases, expanding the
      prevailing view of pathogenesis with important therapeutic implications.

PMID- 22951057
TI  - IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies.
AB  - Decades of research in animal models have provided abundant evidence to show that
      IL-13 is a key T(H)2 cytokine that directs many of the important features of
      airway inflammation and remodeling in patients with allergic asthma. Several
      promising focused therapies for asthma that target the IL-13/IL-4/signal
      transducer and activator of transcription 6 pathway are in development, including
      anti-IL-13 mAbs and IL-4 receptor antagonists. The efficacy of these new
      potential asthma therapies depends on the responsiveness of patients. However, an
      understanding of how IL-13-directed therapies might benefit asthmatic patients is
      confounded by the complex heterogeneity of the disease. Recent efforts to
      classify subphenotypes of asthma have focused on sputum cellular inflammation
      profiles, as well as cluster analyses of clinical variables and molecular and
      genetic signatures. Researchers and clinicians can now evaluate biomarkers of
      T(H)2-driven airway inflammation in asthmatic patients, such as serum IgE levels,
      sputum eosinophil counts, fraction of exhaled nitric oxide levels, and serum
      periostin levels, to aid decision making in clinical trials and drug development
      and to identify subsets of patients who might benefit from therapies. Although it
      is unlikely that these therapies will benefit all asthmatic patients with this
      heterogeneous disease, advances in understanding asthma subphenotypes in relation
      to clinical variables and T(H)2 cytokine responses offer the opportunity to
      improve the efficacy and safety of proposed therapies for asthma.

PMID- 22951058
TI  - The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US
      longitudinal cohort.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common skin disease that is characterized
      by recurrent episodes of itching. Filaggrin (FLG) loss-of-function (FLG null)
      mutations have been associated with an increased risk of AD. OBJECTIVE: We sought
      to evaluate the effect of individual FLG null mutations on the persistence of AD
      over time. METHODS: We evaluated a multiyear prospective cohort study of children
      with AD with respect to FLG null mutations (R501X, 2282del4, R2447X, and S3247X).
      We evaluated the association of these mutations with the persistence of AD
      symptoms over time with respect to reports of no symptoms of AD and whether
      topical medication was needed for symptom resolution. RESULTS: Eight hundred
      fifty-seven subjects were followed for 3684 person-years. One or more FLG null
      mutations were noted in 16.3% of subjects and specifically in 27.5% of white
      subjects and 5.8% of African American subjects. Subjects with an FLG null
      mutation were less likely (odds ratio [OR], 0.54; 95% CI, 0.41-0.71) to report
      that their skin was symptom free at any time compared with those without an FLG
      null mutation. The effect of these mutations was similar in white subjects (OR,
      0.42; 95% CI, 0.31-0.57) and African-American subjects (OR, 0.53; 95% CI, 0.25
      1.12; P = .62). Children with the R501X mutation (OR, 0.44; 95% CI, 0.22-0.88)
      were the least responsive to therapy. CONCLUSIONS: In a US cohort with AD, FLG
      null mutations were common. Children with FLG null mutations were more likely to
      have persistent AD. Although these mutations were more common in those of
      European ancestry, their effect on persistence was similar in those of African
      ancestry. Response to therapy was not uniform among children with FLG null
      mutations.

PMID- 22951059
TI  - Recurrent acute lower-limb ischemia with multiple organ infarctions secondary to
      acute myeloid leukaemia M1.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is usually associated with coagulopathy
      and disorders of hemostasis, but cases of ischemic events have been reported. We
      present a case of AML with recurrent acute limb ischemia and multiple organ
      infarctions. METHODS AND RESULTS: A 57-year-old woman diagnosed with AML subtype
      M1 developed recurrent bilateral acute lower-limb ischemia refractory to multiple
      thromboembolectomies and bypass grafting. Histopathology revealed that thrombi
      were composed of leukemic blasts, and computed tomography angiogram incidentally
      revealed multiple infarctions. She demonstrated a response to chemotherapy, but
      died of an overwhelming sepsis 22 days after her acute admission. CONCLUSIONS:
      AML subtype M1 with acute lower-limb ischemia and multiple organ infarctions is
      associated with a poor prognosis. The role of emergency chemotherapy in reducing
      the tumour burden and possibly improving the results of vascular interventions
      needs to be defined. Limb-salvaging surgery should not be delayed but be
      administered immediately according to the degree of ischemia.

PMID- 22951060
TI  - Aortoiliac thrombi in inflammatory bowel disease.
AB  - Isolated arterial thrombi complicating inflammatory bowel disease occurs rarely.
      We encountered a case of a 28-year-old man with Crohn disease who presented with
      abdominal pain and severe claudication and was found to have an isolated
      aortoiliac thrombus. Bilateral aortoiliac thromboembolectomies were performed
      with successful restoration of femoral blood flow. Long-term anticoagulation
      therapy was instituted after an extensive hypercoagulable workup, which failed to
      reveal an etiology for the patient's coagulopathy. We present our case and
      perform an extensive literature review on this topic.

PMID- 22951061
TI  - Three-dimensional workstation is useful for measuring the correct size of
      abdominal aortic aneurysm diameters.
AB  - BACKGROUND: Abdominal aortic aneurysm diameter is usually measured by the maximum
      minor-axis diameter on axial computed tomography (CT). However, this
      "traditional" diameter may underestimate the real size, as the aorta is not
      always straight and the aneurysm shape is sometimes in the form of an ellipse
      along the cross section. Therefore, we measured maximum major-axis diameters
      using a three-dimensional (3D) workstation and compared them with the traditional
      maximum minor-axis diameters measured using thin-slice axial CT. METHODS: CT data
      of 141 AAA patients (with fusiform aneurysms) were stored in a 3D workstation.
      These thin-slice CT images were reviewed on the 3D workstation to obtain curved
      multiplanar reconstruction images (CPR images). Using the CPR images, we measured
      the maximum major-axis and minor-axis diameters on CPR and the angle of the
      aneurysms to the body axis. RESULTS: The mean traditional maximum minor-axis
      diameter was 51.2 +/- 8.2 mm, whereas the mean maximum major-axis diameter on CPR
      was 54.7 +/- 10.1 mm. Sixty eight patients had a mean aneurysm size of <50 mm
      when measured by the traditional minor-axis diameter. Among these patients, five
      (7.4%) had a major-axis diameter >55 mm on CPR. CONCLUSION: The measurement of
      the traditional maximum minor-axis diameter of aneurysms is useful in the case of
      most patients. However, the traditional maximum minor-axis diameter may
      underestimate the real aneurysmal diameter, particularly in patients with an
      ellipse-shaped aneurysm. The maximum major-axis diameter as measured using CPR
      images is effective for representing the real aneurysmal size.

PMID- 22951062
TI  - Isokinetic strength and endurance in proximal and distal muscles in patients with
      peripheral artery disease.
AB  - BACKGROUND: The objective of this study was to analyze the muscle strength and
      endurance of the proximal and distal lower-extremity muscles in peripheral artery
      disease (PAD) patients. METHODS: Twenty patients with bilateral PAD with symptoms
      of intermittent claudication and nine control subjects without PAD were included
      in the study, comprising 40 and 18 legs, respectively. All subjects performed an
      isokinetic muscle test to evaluate the muscle strength and endurance of the
      proximal (knee extension and knee flexion movements) and distal (plantar flexion
      and dorsiflexion movements) muscle groups in the lower extremity. RESULTS:
      Compared with the control group, the PAD group presented lower muscle strength in
      knee flexion (-14.0%), dorsiflexion (-26.0%), and plantar flexion (-21.2%)
      movements (P < 0.05) but similar strength in knee extension movements (P > 0.05).
      The PAD patients presented a 13.5% lower knee flexion/extension strength ratio
      compared with the control subjects (P < 0.05), as well as lower muscle endurance
      in dorsiflexion (-28.1%) and plantar flexion (-17.0%) movements (P < 0.05). The
      muscle endurance in knee flexion and knee extension movements was similar between
      PAD patients and the control subjects (P > 0.05). CONCLUSION: PAD patients
      present lower proximal and distal muscle strength and lower distal muscle
      endurance than control patients. Therefore, interventions to improve muscle
      strength and endurance should be prescribed for PAD patients.

PMID- 22951063
TI  - Natural history of carotid artery occlusion.
AB  - Carotid artery occlusion (CAO) is a risk factor for stroke ipsilateral to the
      occlusion and puts patients in a high-risk category when contralateral
      endarterectomy is performed. The purpose of this study was to evaluate the long
      term outcomes of patients with internal CAO and to determine risk factors
      predictive of subsequent neurological event, contralateral carotid intervention,
      or death. Patients with internal CAO shown by duplex ultrasonography were
      retrospectively identified and followed between January 2002 and June 2010
      (follow-up: 1-101 months, mean: 52 months) at a tertiary care hospital. All had
      multiple duplex examinations available for review. Chi-square analysis was used
      to determine risk factors for neurologic event, contralateral intervention, or
      all-cause morality. Multivariate Cox proportional hazard analysis was conducted
      using univariate risk factors with P values <0.1. Survival was estimated using
      the Kaplan-Meier method (P < 0.05 significant). Eighty patients with internal CAO
      were identified and available for analysis. On initial encounter, 30 (38%) were
      symptomatic, with 26 (87%) having symptoms referable to the side of the occluded
      internal carotid artery. During follow-up, seven (9%) had a neurologic event, of
      which six (86%) were referable to the occluded side; 14 (18%) patients underwent
      a contralateral operation. Nineteen (24%) patients died during the period of
      study. Although numerous variables of multivessel disease were significant with
      chi(2) analysis, there was no significant risk factor associated with neurologic
      event on multivariate analysis. However, the development of a hemodynamically
      significant stenosis (>50%) or occlusion of the external carotid artery (ECA)
      ipsilateral to the occlusion on follow-up (P < 0.027) was associated with
      increased risk of death. Kaplan-Meier analysis showed 7-year survival for
      patients with ECA disease at follow-up was significantly worse (16.2% +/- 10.3%
      [n = 21] vs. 79% +/- 8.7% [n = 59]; P < 0.00001). Frequently, patients present
      with neurological symptoms referable to the side of the internal CAO. Eighty-six
      percent of neurologic events that occur in follow-up are attributable to the side
      of the occluded carotid, indicating that the occluded side continues to
      contribute to neurologic morbidity over time. Multivariate analysis revealed no
      single factor to be predictive of subsequent neurologic events. With significant
      risk of death in patients found to have ipsilateral ECA stenosis during follow
      up, it seems reasonable to continue surveillance of the occluded carotid.

PMID- 22951064
TI  - Totally implanted venous access devices implanted in the saphenous vein. Relation
      between the reservoir site and comfort/discomfort of the patients.
AB  - BACKGROUND: When a totally implantable venous access device (TIVAD) is implanted
      in the femoral or saphenous vein, the port can be placed in the abdominal wall,
      thigh, or anteroinferior thoracic wall. This study analyzed the relationship
      between the position of the port and patient comfort. METHODS: All patients who
      underwent TIVAD implantation from 1995 to 2011 were included in the study. Sex,
      age, indication for TIVAD implantation, contraindication for implantation in a
      vein draining into the superior vena cava, surgical technique, length of
      procedure, complications, difficulties recorded by nurses, and patient comfort or
      discomfort were recorded. RESULTS: The TIVAD was implanted in the saphenous vein
      in 6 of 581 patients (1.3%) who received a TIVAD, consisting of four male
      subjects and two female subjects aged 35 to 56 years (mean age: 47.3 years), who
      all underwent TIVAD implantation for the treatment of a solid tumor. The port was
      positioned in the anteroinferior thoracic wall in one patient, the abdominal wall
      in one patient, the anterior thigh in three patients, and the lateral thigh in
      one patient. The mean procedure duration was 52 minutes (range: 20-135 minutes).
      No immediate or early complications were recorded. The nurses had difficulty in
      puncturing the port in the abdominal wall. Patient comfort levels were high when
      the port was placed in the anterior thigh. CONCLUSION: The anterior thigh may be
      the most useful and comfortable position for the port of a TIVAD implanted in the
      inferior vena cava. Larger studies should be undertaken to confirm this.

PMID- 22951065
TI  - Aneurysm of a 32-year-old aortorenal saphenous vein bypass graft.
AB  - We report the case of an incidentally discovered aneurysm of a previous saphenous
      vein bypass graft performed 32 years earlier for a renal artery aneurysm. The
      patient is a 52-year-old man who initially suffered from symptoms of hypertension
      and left-sided back pain. Saphenous vein bypass grafting was performed with
      aneurysm resection. Thirty-two years after surgery, the patient underwent a
      magnetic resonance imaging scan for back pain, hip pain, and anemia, discovering
      a 1.8-cm focal aneurysm at the site of the previous bypass. The patient underwent
      a repeat aortorenal bypass with an 8-mm flanged Dacron graft with excision of the
      existing aneurysmal saphenous vein graft.

PMID- 22951066
TI  - Internal jugular vein hemangioma.
AB  - Primary tumors of the major body veins arising intraluminally are rare clinical
      entities. As such, few cases have been reported in the literature. As a primary
      tumor, hemangiomas arising in the internal jugular vein are extremely rare, while
      those arising in the external jugular vein are only slightly more common. We
      present a case of an internal jugular vein hemangioma that was incidentally
      discovered during an ultrasound examination performed for the evaluation of the
      internal carotid arteries. We believe that this is the second case of internal
      jugular vein hemangioma reported in the English literature.

PMID- 22951067
TI  - 'Working with the team': an exploratory study of improved type 2 diabetes
      management in a new model of integrated primary/secondary care.
AB  - This study aimed to explore how a new model of integrated primary/secondary care
      for type 2 diabetes management, the Brisbane South Complex Diabetes Service
      (BSCDS), related to improved diabetes management in a selected group of patients.
      We used a qualitative research design to obtain detailed accounts from the BSCDS
      via semi-structured interviews with 10 patients. The interviews were fully
      transcribed and systematically coded using a form of thematic analysis.
      Participants' responses were grouped in relation to: (1) Patient-centred care;
      (2) Effective multiprofessional teamwork; and (3) Empowering patients. The key
      features of this integrated primary/secondary care model were accessibility and
      its delivery within a positive health care environment, clear and supportive
      interpersonal communication between patients and health care providers, and
      patients seeing themselves as being part of the team-based care. The BSCDS
      delivered patient-centred care and achieved patient engagement in ways that may
      have contributed to improved type 2 diabetes management in these participants. 

PMID- 22951068
TI  - Epidemiology of pain among outpatients in methadone maintenance treatment
      programs.
AB  - BACKGROUND: This analysis explored the prevalence and correlates of pain in
      patients enrolled in methadone maintenance treatment (MMT). METHODS: Patients in
      two MMT programs starting a hepatitis care coordination randomized controlled
      trial completed the Brief Pain Inventory Short-Form and other questionnaires.
      Associations between clinically significant pain (average daily pain>=5 or mean
      pain interference>=5 during the past week) and sociodemographic data, medical
      status, depressive symptoms, and health-related quality of life, and current
      substance use were evaluated in multivariate analyses. RESULTS: The 489 patients
      included 31.8% women; 30.3% Hispanics, 29.4% non-Hispanic Blacks, and 36.0% non
      Hispanic Whites; 60.1% had hepatitis C, 10.6% had HIV, and 46.8% had moderate or
      severe depressive symptomatology. Mean methadone dose was 95.7mg (SD 48.9) and
      urine drug screening (UDS) was positive for opiates, cocaine, and amphetamines in
      32.9%, 40.1%, and 2.9%, respectively. Overall, 237 (48.5%) reported clinically
      significant pain. Pain treatments included prescribed opioids (38.8%) and non
      opioids (48.9%), and self-management approaches (60.8%), including prayer
      (33.8%), vitamins (29.5%), and distraction (12.7%). Pain was associated with
      higher methadone dose, more medical comorbidities, prescribed opioid therapy, and
      more severe depressive symptomatology; it was not associated with UDS or self
      reported substance use. CONCLUSIONS: Clinically significant pain was reported by
      almost half of the patients in MMT programs and was associated with medical and
      psychological comorbidity. Pain was often treated with opioids and was not
      associated with measures of drug use. Studies are needed to further clarify these
      associations and determine their importance for pain treatment strategies.

PMID- 22951069
TI  - Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the
      genome by association with GATA3.
AB  - BACKGROUND: The TCF7L2 transcription factor is linked to a variety of human
      diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2
      could influence expression of genes involved in diverse diseases is by binding to
      distinct regulatory regions in different tissues. To test this hypothesis, we
      performed ChIP-seq for TCF7L2 in six human cell lines. RESULTS: We identified
      116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to the
      six cell lines. Using ChIP-seq, we showed that many genomic regions that are
      marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that
      TCF7L2 plays a critical role in enhancer activity. Bioinformatic analysis of the
      cell type-specific TCF7L2 binding sites revealed enrichment for multiple
      transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and
      the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co
      localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells.
      Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites
      but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis
      suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test
      this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding
      was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses
      transcription when tethered to the genome via GATA3. CONCLUSIONS: Our studies
      demonstrate a novel relationship between GATA3 and TCF7L2, and reveal important
      insights into TCF7L2-mediated gene regulation.

PMID- 22951070
TI  - Neuroimaging correlates of pathologically defined subtypes of Alzheimer's
      disease: a case-control study.
AB  - BACKGROUND: Three subtypes of Alzheimer's disease (AD) have been pathologically
      defined on the basis of the distribution of neurofibrillary tangles: typical AD,
      hippocampal-sparing AD, and limbic-predominant AD. Compared with typical AD,
      hippocampal-sparing AD has more neurofibrillary tangles in the cortex and fewer
      in the hippocampus, whereas the opposite pattern is seen in limbic-predominant
      AD. We aimed to determine whether MRI patterns of atrophy differ between these
      subtypes and whether structural neuroimaging could be a useful predictor of
      pathological subtype at autopsy. METHODS: We identified patients who had been
      followed up in the Mayo Clinic Alzheimer's Disease Research Center (Rochester,
      MN, USA) or in the Alzheimer's Disease Patient Registry (Rochester, MN, USA)
      between 1992 and 2005. To be eligible for inclusion, participants had to have had
      dementia, AD pathology at autopsy (Braak stage >=IV and intermediate to high
      probability of AD), and an ante-mortem MRI. Cases were assigned to one of three
      pathological subtypes--hippocampal-sparing, limbic-predominant, and typical AD-
      on the basis of neurofibrillary tangle counts in hippocampus and cortex and ratio
      of hippocampal to cortical burden, without reference to neuronal loss. Voxel
      based morphometry and atlas-based parcellation were used to compare patterns of
      grey matter loss between groups and with age-matched control individuals.
      Neuroimaging was obtained at the time of first presentation. To summarise pair
      wise group differences, we report the area under the receiver operator
      characteristic curve (AUROC). FINDINGS: Of 177 eligible patients, 125 (71%) were
      classified as having typical AD, 33 (19%) as having limbic-predominant AD, and 19
      (11%) as having hippocampal-sparing AD. Most patients with typical (98 [78%]) and
      limbic-predominant AD (31 [94%]) initially presented with an amnestic syndrome,
      but fewer patients with hippocampal-sparing AD (eight [42%]) did. The most severe
      medial temporal atrophy was recorded in patients with limbic-predominant AD,
      followed by those with typical disease, and then those with hippocampal-sparing
      AD. Conversely, the most severe cortical atrophy was noted in patients with
      hippocampal-sparing AD, followed by those with typical disease, and then limbic
      predominant AD. The ratio of hippocampal to cortical volumes allowed the best
      discrimination between subtypes (p<0.0001; three-way AUROC 0.52 [95% CI 0.47
      0.52]; ratio of AUROC to chance classification 3.1 [2.8-3.1]). Patients with
      typical AD and non-amnesic initial presentation had a significantly higher ratio
      of hippocampal to cortical volumes (median 0.045 [IQR 0.035-0.056]) than did
      those with an amnesic presentation (0.041 [0.031-0.057]; p=0.001).
      INTERPRETATION: Patterns of atrophy on MRI differ across the pathological
      subtypes of AD. MRI regional volumetric analysis can reliably track the
      distribution of neurofibrillary tangle pathology and can predict pathological
      subtype of AD at autopsy. FUNDING: US National Institutes of Health (National
      Institute on Aging).

PMID- 22951071
TI  - The effects of N-acetyl-L-cysteine supplementation on in vitro porcine oocyte
      maturation and subsequent fertilisation and embryonic development.
AB  - The effects of supplementation with 1.5 mM n-acetyl-l-cysteine (NAC) during in
      vitro oocyte maturation were studied. Oocytes were supplemented with 1.5 mM NAC
      during maturation for 0 to 24 h, 24 to 48 h, or 0 to 48 h then subjected to IVF
      and embryo development. Oocytes were evaluated after maturation for intracellular
      glutathione concentration, superoxide dismutase and glutathione peroxidase
      activities and DNA fragmentation. Fertilisation and embryonic development success
      were also evaluated. There was no effect of treatment on intracellular
      glutathione concentrations, enzyme activities or fertilisation success rates.
      Supplementing NAC during maturation significantly decreased (P < 0.05) the
      percentage of oocytes with fragmented DNA compared with no NAC supplementation.
      Supplementing NAC from 24 to 48 h or 0 to 48 h resulted in a significantly higher
      (P < 0.05) percentage of oocytes with male pronuclei than for oocytes from the
      other treatment groups. There was no difference in the percentage of embryos
      cleaved by 48 h after IVF between treatment groups. Supplementing NAC from 24 to
      48 h or 0 to 48 h resulted in a significantly higher (P < 0.05) percentage of
      embryos reaching the blastocyst stage by 144 h after IVF compared with the other
      treatment groups. These results indicate that supplementation of the oocyte
      maturation medium with 1.5 mM NAC, specifically during the last 24 h, improves
      male pronucleus formation and blastocyst development in pigs.

PMID- 22951072
TI  - The cost-effectiveness of screening for anal cancer in men who have sex with men:
      a systematic review.
AB  - Anal cancer is a relatively rare neoplasm, related to human papillomavirus (HPV),
      with an incidence that does not warrant general screening. However, as many cases
      occur in identifiable high-risk populations, targeting these groups may be cost
      effective. Screening for anal cancer in men who have sex with men (MSM) may be
      appropriate, given their elevated risk of anal cancer. Examining existing cost
      effectiveness analyses can help inform the design and conduct of future clinical
      and economic studies.A review of the literature was performed using three
      databases to identify studies that assessed the cost-effectiveness of anal cancer
      screening in MSM. Five analyses were identified: four modelled the cost
      effectiveness of cytological screening over a patient's lifetime, and estimated
      final health outcomes as survival or quality adjusted survival. The fifth
      presented a decision analysis with intermediate health outcomes only and did not
      extrapolate to longer-term health outcomes.Several factors influenced the
      incremental cost-effectiveness ratios. These factors were related to a paucity of
      primary data and included: availability of longer-term epidemiological and
      natural history data; availability of utility-based quality of life data from an
      appropriate respondent population; appropriate resource use information; and
      availability of information on screening adherence.There is considerable
      uncertainty in model results: analyses from the United States suggest screening
      is almost always cost-effective; analyses from the United Kingdom suggest that
      screening is unlikely to be cost-effective. Uncertainty is primarily driven by
      data paucity; by summarising key uncertainties in existing models, this review
      can inform the design and conduct of future studies.

PMID- 22951073
TI  - Redox control of cell proliferation.
AB  - Cell proliferation is regulated by multiple signaling pathways and stress
      surveillance systems to ensure cell division takes place with fidelity. In
      response to oxidative stress, cells arrest in the cell-cycle and aberrant redox
      control of proliferation underlies the pathogenesis of many diseases including
      cancer and neurodegenerative disorders. Redox sensing of cell-cycle regulation
      has recently been shown to involve reactive cysteine thiols that function as
      redox sensors in cell-cycle regulators. By modulating cell-cycle regulators these
      redox-active thiols ensure cell division is executed at the right redox
      environment. This review summarizes recent findings on regulation of cell
      division by the oxidation of cysteines in cell division regulators and the
      potential of targeting these critical cysteine residues for cancer therapy.

PMID- 22951074
TI  - Novel aromatase inhibitors by structure-guided design.
AB  - Human cytochrome P450 aromatase catalyzes with high specificity the synthesis of
      estrogens from androgens. Aromatase inhibitors (AIs) such as exemestane, 6
      methylideneandrosta-1,4-diene-3,17-dione, are preeminent drugs for the treatment
      of estrogen-dependent breast cancer. The crystal structure of human placental
      aromatase has shown an androgen-specific active site. By utilization of the
      structural data, novel C6-substituted androsta-1,4-diene-3,17-dione inhibitors
      have been designed. Several of the C6-substituted 2-alkynyloxy compounds inhibit
      purified placental aromatase with IC(50) values in the nanomolar range.
      Antiproliferation studies in a MCF-7 breast cancer cell line demonstrate that
      some of these compounds have EC(50) values better than 1 nM, exceeding that for
      exemestane. X-ray structures of aromatase complexes of two potent compounds
      reveal that, per their design, the novel side groups protrude into the opening to
      the access channel unoccupied in the enzyme-substrate/exemestane complexes. The
      observed structure-activity relationship is borne out by the X-ray data.
      Structure-guided design permits utilization of the aromatase-specific
      interactions for the development of next generation AIs.

PMID- 22951075
TI  - Prospective, randomized, multicenter study evaluating safety and efficacy of
      intragastric dual-balloon in obesity.
AB  - BACKGROUND: Intragastric balloons are designed to occupy space within the stomach
      and induce satiety. The present study evaluated the safety and efficacy of an
      intragastric dual balloon as an adjunct to diet and exercise in obese patients
      compared with diet and exercise alone. METHODS: After approval from the
      institutional review board, patients provided written consent and were randomized
      to the treatment group (TG) or control group (CG) in a 2:1 ratio. Three sites
      randomized a total of 30 patients to the TG (n = 21) or CG (n = 9). Patients
      randomized to the TG underwent endoscopic placement of the dual balloon. Both
      groups received similar diet and exercise counseling. After 24 weeks, the device
      was removed. Patient weight, adverse events, and quality of life data were
      evaluated throughout the 48-week study duration. RESULTS: Our patient population
      included 26 women and 4 men aged 26-59 years. At 24 weeks, the mean excess weight
      loss in the TG and CG was 31.8% +/- 21.3% and 18.3% +/- 20.9%, respectively (P =
      .1371). At 48 weeks, 24 weeks after device removal, the TG maintained 64% of
      their weight loss. No deaths, unanticipated adverse effects, early removals,
      balloon deflations, or balloon migrations occurred. In the TG, 4 patients were
      readmitted for severe nausea, 1 had asymptomatic gastritis at balloon removal,
      and 1 patient experienced transient hypoxia during device removal. CONCLUSION: In
      the present small study, the dual balloon proved easy to use, was associated with
      a trend toward greater weight loss than the CG, and demonstrated a good safety
      profile.

PMID- 22951076
TI  - Laparoscopic sleeve gastrectomy in Chinese female patient with Prader-Willi
      syndrome and diabetes.

PMID- 22951077
TI  - Two-year follow-up of wound complications associated with laparoendoscopic single
      site adjustable gastric banding.
AB  - BACKGROUND: In an effort to provide better cosmesis for patients, there has been
      a surge recently in the use of laparoendoscopic single-site adjustable gastric
      banding. Few data, however, are available on the long-term wound complications
      resulting from this technique. We conducted a retrospective review of patients to
      identify the extent of wound complications found during a minimum follow-up
      period of 2 years after laparoendoscopic single-site adjustable gastric banding.
      The complications evaluated included infection, hernia rates, and port and tubing
      complications. All the laparoendoscopic single-site adjustable gastric banding
      cases were performed at University of Illinois Medical Center by a single
      surgeon. METHODS: Twenty-five patients underwent single-site laparoscopic
      adjustable gastric banding from March 2009 to January 2010, and the data were
      reviewed retrospectively. The single incision was made with multifascial trocar
      placement using conventional laparoscopic instruments. The patients were followed
      up during band adjustments and clinic visits and by telephone interview. RESULTS:
      Six months after surgery, 1 patient required port removal because of port site
      infection with internalization of the tubing. A second patient experienced a foul
      smelling, clear discharge and was treated with antibiotics, with no additional
      consequences. No incisional hernias or flipped ports were noted. CONCLUSION: In
      our experience, laparoendoscopic single-site adjustable gastric banding produced
      a low rate of port and wound site complications in patients during a minimum
      follow-up period of 2 years. We believe this is a valid alternative to the
      standard procedure, providing cosmetic advantages and a low wound complication
      rate in morbidly obese patients.

PMID- 22951078
TI  - Gastrointestinal function and eating behavior after gastric bypass and duodenal
      switch.
AB  - BACKGROUND: Duodenal switch provides greater weight loss than gastric bypass in
      severely obese patients; however, comparative data on the changes in
      gastrointestinal symptoms, bowel function, eating behavior, dietary intake, and
      psychosocial functioning are limited. METHODS: The setting for the present study
      was 2 university hospitals in Norway and Sweden. Participants with a body mass
      index of 50-60 kg/m(2) were randomly assigned to gastric bypass (n = 31) or
      duodenal switch (n = 29) and followed up for 2 years. Of the 60 patients, 97%
      completed the study. Their mean weight decreased by 31.2% after gastric bypass
      and 44.8% after duodenal switch. At inclusion and 1 and 2 years of follow-up, the
      participants completed the Gastrointestinal Symptom Rating Scale, a bowel
      function questionnaire, the Three-Factor Eating Questionnaire-R21, a 4-day food
      record, and the Obesity-related Problems scale. RESULTS: Compared with the
      gastric bypass group, the duodenal switch group reported more symptoms of
      diarrhea (P = .0002), a greater mean number of daytime defecations (P = .007),
      and more anal leakage of stool (50% versus 18% of participants, respectively; P =
      .015) after 2 years. The scores for uncontrolled and emotional eating were
      significantly and similarly reduced after both operations. The mean total caloric
      intake and intake of fat and carbohydrates were significantly reduced in both
      groups. Protein intake was significantly reduced only after gastric bypass (P =
      .008, between-group comparison). Psychosocial function was significantly improved
      after both operations (P = .23, between the 2 groups). CONCLUSION:
      Gastrointestinal side effects and anal leakage of stool were more pronounced
      after duodenal switch than after gastric bypass. Both procedures led to reduced
      uncontrolled and emotional eating, reduced caloric intake, and improved
      psychosocial functioning.

PMID- 22951079
TI  - Effect of Helicobacter pylori on marginal ulcer and stomal stenosis after Roux-en
      Y gastric bypass.
AB  - BACKGROUND: Conflicting data have been published regarding whether Helicobacter
      pylori (HP) positivity is associated with increased complication rates in
      patients undergoing Roux-en-Y gastric bypass (RYGB). METHODS: We retrospectively
      examined the rate of complications in patients undergoing RYGB according to
      preoperative HP positivity and persistent post-treatment positivity to determine
      whether a correlation exists. RESULTS: A total of 228 patients underwent RYGB
      during a 2-year period (2009-2011). No patient had evidence of active ulcer
      disease on preoperative endoscopy. Of the 228 patients, 68 tested positive for HP
      on serum antigen screening and were treated with omeprazole, clarithromycin, and
      amoxillin. After treatment, 24 patients were persistently positive on repeat
      endoscopic biopsy. Of the 228 patients, 12 experienced a total of 13
      complications (stomal stenosis in 8, marginal ulcer in 5, and none with
      anastomotic leak or gastrointestinal bleeding). Of the 68 patients with HP
      positivity preoperatively, 1 complication (2.3%) developed in the 44 patients who
      had responded to triple therapy, and no complications occurred in the 24 patients
      who had remained positive after treatment (P = 1.00), showing no difference.
      Also, no significant difference was found in the rate of complications (P = .11)
      between patients who were HP negative preoperatively (11 of 160, 6.9%) and those
      who were positive preoperatively (1 of 68, 1.5%). CONCLUSION: HP status, whether
      positive preoperatively or persistently positive after treatment, had no effect
      on the marginal ulcer or stomal stenosis rates in patients undergoing RYGB in the
      present study.

PMID- 22951080
TI  - Women's knowledge, attitudes and practice about breast cancer screening in the
      region of Monastir (Tunisia).
AB  - Breast cancer remains a worldwide public health problem. In Tunisia, it is
      considered to be the primary women's cancer and causes high morbidity and
      mortality. This study aimed to investigate female knowledge, attitudes and
      practice of breast cancer screening in the region of Monastir (Tunisia). We
      conducted a descriptive cross-sectional design exploring knowledge, attitudes and
      practices of women in the region of Monastir on breast cancer screening. The
      study was conducted in health centres of this region from 1 March 2009 to 30 June
      2009. Data were collected via a structured questionnaire containing 15 items on
      demographic status, knowledge of risk factors and screening methods and attitudes
      towards the relevance and effectiveness of breast cancer screening. A scoring
      scheme was used to score women's responses. A total of 900 women agreed to take
      part in the study. Their mean age was 41.6+/-12.4 years and 64% did not exceed
      the primary level of education. According to the constructed scores, 92% of
      participants had poor knowledge of the specific risk factors for breast cancer
      and 63.2% had poor knowledge of the screening methods. Proper practice of breast
      cancer screening was observed in 14.3% of cases. Multiple logistic regression
      analysis showed that good knowledge of risk factors and screening methods, higher
      level of education and positive family history of breast cancer were
      independently correlated with breast cancer screening practice. This study
      revealed poor knowledge of breast cancer and the screening methods as well as low
      levels of practice of breast cancer screening among women in the region of
      Monastir. Results justify educational programs to raise women's adherence to
      breast cancer screening programs in Tunisia.

PMID- 22951081
TI  - Gabapentin: a suppressant for refractory chronic cough.

PMID- 22951083
TI  - The battle against stent thrombosis--to protect and to serve.

PMID- 22951084
TI  - Gabapentin for refractory chronic cough: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Refractory chronic cough causes substantial symptoms and quality-of
      life impairment. Similarities between central reflex sensitisation in refractory
      chronic cough and neuropathic pain suggest that neuromodulators such as
      gabapentin might be effective for refractory chronic cough. We established the
      efficacy of gabapentin in patients with refractory chronic cough. METHODS: This
      randomised, double-blind, placebo-controlled trial was undertaken at an
      outpatient clinic in Australia. Adults with refractory chronic cough (>8 weeks'
      duration) without active respiratory disease or infection were randomly assigned
      to receive gabapentin (maximum tolerable daily dose of 1800 mg) or matching
      placebo for 10 weeks. Block randomisation was done with randomisation generator
      software, stratified by sex. Patients and investigators were masked to assigned
      treatment. The primary endpoint was change in cough-specific quality of life
      (Leicester cough questionnaire [LCQ] score) from baseline to 8 weeks of
      treatment, analysed by intention to treat. This study is registered with the
      Australian New Zealand Clinical Trials Registry, number ACTRN12608000248369.
      FINDINGS: 62 patients were randomly assigned to gabepentin (n=32) or placebo
      (n=30) and ten patients withdrew before the study end. Gabapentin significantly
      improved cough-specific quality of life compared with placebo (between-group
      difference in LCQ score during treatment period 1.80, 95% CI 0.56-3.04; p=0.004;
      number needed to treat of 3.58). Side-effects occurred in ten patients (31%)
      given gabapentin (the most common being nausea and fatigue) and three (10%) given
      placebo. INTERPRETATION: The treatment of refractory chronic cough with
      gabapentin is both effective and well tolerated. These positive effects suggest
      that central reflex sensitisation is a relevant mechanism in refractory chronic
      cough. FUNDING: National Health and Medical Research Council of Australia and
      Hunter Medical Research Institute, Newcastle, Australia.

PMID- 22951085
TI  - Exposure to bisphenol A results in a decline in mouse spermatogenesis.
AB  - Bisphenol A (BPA), a chemical used in many consumer products, interferes with the
      endocrine system of mammals, including humans. The aim of the present study was
      to investigate the effect of BPA on spermatogenesis and semen quality. The
      objective of this study was to assess the effects of BPA on mouse
      spermatogenesis. CD1 mice were used in all experiments. Mice were treated with
      different doses of BPA (0, 20 and 40 MUg kg-1 day-1 from postnatal Day (PND) 3 to
      PND21, PND 35 or PND49. After 5 weeks BPA treatment, oestrogen receptor alpha
      expression was increased in mouse testis, whereas the meiotic progression of germ
      cells was slowed. Thus, both the quality and quantity of spermatozoa were
      decreased in 7-week-old mice. However, BPA had no effect on DNA methylation of
      imprinted genes such as Igf2, Igf2r, Peg3 and H19, in germ cells. In addition,
      exposure of male mice to BPA resulted in abnormal offspring that were smaller
      with a low-quality pelage when they were 35 days old. In conclusion, BPA hampers
      spermatogenesis and the subsequent development of offspring.

PMID- 22951086
TI  - The place of robotics in gynecologic surgery.
AB  - Robot-assisted laparoscopic gynecologic surgery has undergone widespread
      development in recent years. The surgical literature on this subject continues to
      grow. The goal of this article is to summarize the principal indications for
      robotic assistance in gynecologic surgery and to offer a general overview of the
      principal articles dealing with robotic surgery for both benign and malignant
      disease.

PMID- 22951087
TI  - Outcomes and opportunities: a nurse-led model of chronic disease management in
      Australian general practice.
AB  - The Australian government's commitment to health service reform has placed
      general practice at the centre of its agenda to manage chronic disease. Concerns
      about the capacity of GPs to meet the growing chronic disease burden has
      stimulated the implementation and testing of new models of care that better
      utilise practice nurses (PN). This paper reports on a mixed-methods study nested
      within a larger study that trialled the feasibility and acceptability of a new
      model of nurse-led chronic disease management in three general practices.
      Patients over 18 years of age with type 2 diabetes, hypertension or stable
      ischaemic heart disease were randomised into PN-led or usual GP-led care. Primary
      outcomes were self-reported quality of life and perceptions of the model's
      feasibility and acceptability from the perspective of patients and GPs. Over the
      12-month study quality of life decreased but the trend between groups was not
      statistically different. Qualitative data indicate that the PN-led model was
      acceptable and feasible to GPs and patients. It is possible to extend the scope
      of PN care to lead the routine clinical management of patients' stable chronic
      diseases. All GPs identified significant advantages to the model and elected to
      continue with the PN-led care after our study concluded. 

PMID- 22951082
TI  - Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting
      or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open
      label, controlled trial.
AB  - BACKGROUND: We sought to compare the long-term safety of two devices with
      different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E
      ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis,
      Johnson & Johnson) in a broad group of patients and lesions. METHODS: Between May
      21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting
      countries to participate in this open-label, multicentre, randomised, superiority
      trial. Eligible patients were those aged 18 years or older undergoing elective,
      unplanned, or emergency procedures in native coronary arteries. Patients were
      randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation
      was stratified per centre with varying block sizes of four, six, or eight
      patients, and concealed with a central telephone-based or web-based allocation
      service. The primary outcome was definite or probable stent thrombosis at 3 years
      and was analysed by intention to treat. Patients and investigators were aware of
      treatment assignment. This trial is registered with ClinicalTrials.gov, number
      NCT00476957. FINDINGS: PROTECT randomised 8791 patients, of whom 8709 provided
      consent to participate and were eligible: 4357 were allocated to the E-ZES group
      and 4352 patients to the C-SES group. At 3 years, rates of definite or probable
      stent thrombosis did not differ between groups (1.4% for E-ZES [predicted: 1.5%]
      vs 1.8% [predicted: 2.5%] for C-SES; hazard ratio [HR] 0.81, 95% CI 0.58-1.14,
      p=0.22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge,
      7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years.
      INTERPRETATION: No evidence of superiority of E-ZES compared with C-SES in
      definite or probable stent thrombosis rates was noted at 3 years. Time analysis
      suggests a difference in definite or probable stent thrombosis between groups is
      emerging over time, and a longer follow-up is therefore needed given the clinical
      relevance of stent thrombosis. FUNDING: Medtronic, Inc.

PMID- 22951088
TI  - Ventricular tachycardia in coronary artery disease.
AB  - Ventricular arrhythmias are important contributors to morbidity and mortality in
      patients with coronary artery disease. Ventricular fibrillation accounts for the
      majority of deaths occurring in the acute phase of ischemia, whereas sustained,
      monomorphic ventricular tachycardia due to reentry generated in the scar tissue
      develops most often in the setting of healed myocardial infarction, especially in
      patients with lower left ventricular ejection fraction. Despite determinant
      advances in population education and myocardial infarction management, the
      ventricular tachycardia risk in the overall population with coronary artery
      disease continues to be a major problem in clinical practice. The initial
      evaluation of a patient presenting with ventricular tachycardia requires a 12
      lead electrocardiogram, which can be helpful to confirm the diagnosis, suggest
      the presence of potential underlying heart disease, and identify the location of
      the ventricular tachycardia circuit. An invasive electrophysiologic study is
      usually crucial to determine the mechanism of the arrhythmia once induced and to
      provide guidance for ablation. The approach for ventricular tachycardia ablation
      depends on several factors, including inducibility, sustainability, and clinical
      tolerance of ventricular tachycardia. The paper also reviews other therapeutic
      options for patients with ventricular tachycardia associated with coronary artery
      disease, including antiarrhythmic drug therapy, surgical ablation, and current
      implantable cardioverter-defibrillator indications.

PMID- 22951089
TI  - Relationship of central and peripheral blood pressure to left ventricular mass in
      hypertensive patients.
AB  - INTRODUCTION AND OBJECTIVES: The purpose of the present study was to assess the
      relationship of central and peripheral blood pressure to left ventricular mass.
      METHODS: Cross-sectional study that included 392 never treated hypertensive
      individuals. Measurement of office, 24-h ambulatory, and central blood pressure
      (obtained using applanation tonometry) and determination of left ventricular mass
      by echocardiography were performed in all patients. RESULTS: In a multiple
      regression analysis, with adjustment for age, gender and metabolic syndrome, 24-h
      blood pressure was more closely related to ventricular mass than the respective
      office and central blood pressures. Systolic blood pressures always exhibited a
      higher correlation than diastolic blood pressures in all 3 determinations. The
      correlation between left ventricular mass index and 24-h systolic blood pressure
      was higher than that of office (P<.002) or central systolic blood pressures
      (P<.002). Changes in 24-h systolic blood pressure caused the greatest variations
      in left ventricular mass index (P<.001). CONCLUSIONS: In our population of
      untreated middle-aged hypertensive patients, left ventricular mass index is more
      closely related to 24-h ambulatory blood pressure than to office or central blood
      pressure. Central blood pressure does not enable us to better identify patients
      with left ventricular hypertrophy.

PMID- 22951090
TI  - Emerging roles of immune cells in luteal angiogenesis.
AB  - In the mammalian ovary, the corpus luteum (CL) is a unique transient endocrine
      organ displaying rapid angiogenesis and time-dependent accumulation of immune
      cells. The CL closely resembles 'transitory tumours', and the rate of luteal
      growth equals that of the fastest growing tumours. Recently, attention has
      focused on multiple roles of immune cells in luteal function, not only in
      luteolysis (CL disruption by immune responses involving T lymphocytes and
      macrophages), but also in CL development (CL remodelling by different immune
      responses involving neutrophils and macrophages). Neutrophils and macrophages
      regulate angiogenesis, lymphangiogenesis, and steroidogenesis by releasing
      cytokines in the CL. In addition, functional polarisation of neutrophils
      (proinflammatory N1 vs anti-inflammatory N2) and macrophages (proinflammatory M1
      vs anti-inflammatory M2) has been demonstrated. This new concept concurs with the
      phenomenon of immune function within the luteal microenvironment: active
      development of the CL infiltrating anti-inflammatory N2 and M2 versus luteal
      regression together with proinflammatory N1 and M1. Conversely, excessive
      angiogenic factors and leucocyte infiltration result in indefinite disordered
      tumour development. However, the negative feedback regulator vasohibin-1 in the
      CL prevents excessive tumour-like vasculogenesis, suggesting that CL development
      has well coordinated time-dependent mechanisms. In this review, we discuss the
      physiological roles of immune cells involved in innate immunity (e.g. neutrophils
      and macrophages) in the local regulation of CL development with a primary focus
      on the cow.

PMID- 22951091
TI  - Sequential generations of honey bee (Apis mellifera) queens produced using
      cryopreserved semen.
AB  - Much of the world's food production is dependent on honey bees for pollination,
      and expanding food production will further increase the demand for managed
      pollination services. Apiculturists outside the native range of the honey bee, in
      the Americas, Australia and eastern Asia, have used only a few of the 27
      described subspecies of honey bees (Apis mellifera) for beekeeping purposes.
      Within the endemic ranges of a particular subspecies, hybridisation can threaten
      native subspecies when local beekeepers import and propagate non-native honey
      bees. For many threatened species, cryopreserved germplasm can provide a resource
      for the preservation of diversity and recovery of endangered populations.
      However, although instrumental insemination of queen honey bees is well
      established, the absence of an effective means to cryopreserve honey bee semen
      has limited the success of efforts to preserve genetic diversity within the
      species or to develop repositories of honey bee germplasm for breeding purposes.
      Herein we report that some queens inseminated with cryopreserved semen were
      capable of producing a substantial number of fertilised offspring. These diploid
      female larvae were used to produce two additional sequential generations of new
      queens, which were then back-crossed to the same stock of frozen semen. Our
      results demonstrate the ability to produce queens using cryopreserved honey bee
      spermatozoa and the potential for the establishment of a honey bee genetic
      repository.

PMID- 22951093
TI  - Actin nucleator Arp2/3 complex is essential for mouse preimplantation embryo
      development.
AB  - The Arp2/3 complex is a critical actin nucleator, which promotes actin assembly
      and is widely involved in a diverse range of actin-related processes such as cell
      locomotion, phagocytosis and the establishment of cell polarity. Previous studies
      showed that the Arp2/3 complex regulates spindle migration and asymmetric
      division during mouse oocyte maturation; however, the role of the Arp2/3 complex
      in early mouse embryo development is still unknown. The results of the present
      study show that the Arp2/3 complex is critical for cytokinesis during mouse
      embryo development. The Arp2/3 complex was concentrated at the cortex of each
      cell at the 2- to 8-cell stage and the peripheral areas of the morula and
      blastocyst. Inhibition of the Arp2/3 complex by the specific inhibitor CK666 at
      the zygote stage caused a failure in cell division; mouse embryos failed to
      undergo compaction and lost apical-basal polarity. The actin level decreased in
      the CK666-treated group, and two or more nuclei were observed within a single
      cell, indicating a failure of cell division. Addition of CK666 at the 8-cell
      stage caused a failure of blastocyst formation, and CDX2 staining confirmed the
      loss of embryo polarity and the failure of trophectoderm and inner cell mass
      formation. Taken together, these data suggest that the Arp2/3 complex may
      regulate mouse embryo development via its effect on cell division.

PMID- 22951094
TI  - Australian health policy makers' priorities for research synthesis: a survey.
AB  - OBJECTIVES: Health policy making is complex, but can be informed by evidence of
      what works, including systematic reviews. We aimed to inform the work of the
      Cochrane Effective Practice and Organisation of Care (EPOC) Group by identifying
      systematic review topics relevant to Australian health policy makers and
      exploring whether existing Cochrane reviews address these topics. METHODS: We
      interviewed 30 senior policy makers from State and Territory Government
      Departments of Health to identify topics considered important for systematic
      reviews within the scope of health services research, including professional,
      financial, organisational and regulatory interventions to improve professional
      practice and the organisation of services. We then looked for existing Cochrane
      reviews relevant to these topics. RESULTS: Eighty-five priority topics were
      identified by policy makers, including advanced practice roles, care for
      Indigenous Australians, care for chronic disease, coordinating across
      jurisdictions, admission avoidance, and eHealth. Sixty published Cochrane reviews
      address these issues, and 34 additional reviews are in progress. Thirty-four
      topics are yet to be addressed. CONCLUSIONS: This survey has identified questions
      for which Australian policy makers have indicated a need for systematic reviews.
      Further, it has confirmed that existing reviews do address issues of importance
      to policy makers, with the potential to inform policy processes.

PMID- 22951095
TI  - The novelty of the "Accordion Grating Illusion".

PMID- 22951096
TI  - Emerging real-time technologies in molecular medicine and the evolution of
      integrated 'pharmacomics' approaches to personalized medicine and drug discovery.
AB  - The advent of real-time macromolecular sequencing is opening the way for new
      levels of understanding of dynamic biological states and new approaches to point
      of-care diagnosis and drug discovery. This fast-growing area promises
      unprecedented capacity to develop detailed descriptions of biosystems in health
      and disease that integrate features from both inherent trait analysis (e.g. by
      genotyping) and dynamic analysis of transient states (e.g. by transcriptome or
      proteome typing). This evolving, integrated 'pharmacomics' will facilitate the
      characterization and monitoring of disease states and drug responses in terms of
      perturbations of biosystems from optimal states. This review considers how the
      latest generation of advances in ultra-rapid macromolecular sequencing will
      accelerate the evolution of personalized medicine and more systematic, rational
      drug discovery.

PMID- 22951097
TI  - Clients' experience of brief lifestyle interventions by community nurses.
AB  - Lifestyle modification interventions in primary health care settings are an
      important means of addressing lifestyle risk factors. An essential factor for the
      success of lifestyle advice is the client's acceptance. Lifestyle interventions
      offered in general practice are well accepted by clients. However, little is
      known about how lifestyle interventions are accepted if offered by community
      nurses in the client's home. This study investigates the experience and
      perspectives of clients who were offered brief lifestyle interventions from
      community nurses, based on the 5As model. Semi-structured interviews were
      conducted with 20 clients who had received brief lifestyle interventions from
      community nurses as part of a larger intervention trial. All clients perceived
      the provision of lifestyle interventions to be an appropriate part of the
      community nurses' role. The advice and support offered was useful only to some,
      depending on personal preferences, experiences, perceived lifestyle risk and self
      rated health. Offering brief lifestyle interventions did not affect the rapport
      between client and nurse and this puts community nurses in an ideal place to
      address lifestyle issues that can sometimes be sensitive. However, client
      centredness must be emphasised to improve clients' uptake of lifestyle advice and
      support.

PMID- 22951099
TI  - Ambulatory blood pressure monitoring should be included in the National Health
      and Nutritional Examination Survey (NHANES).

PMID- 22951098
TI  - 'Eat coffee candy and die': sex, death and Huli funerals.
AB  - BACKGROUND: Sex and death have traditionally been linked in Huli culture in the
      Southern Highlands in Papua New Guinea. Huli regarded that close contact with
      women could result in men becoming sick or dying. However, there has been rapid
      social and economic development in the area and Huli traditions are changing. At
      the same time, HIV prevalence is rising. METHODS: Twenty-five semistructured in
      depth interviews were carried out with key informants during a study on HIV risk
      in the Southern Highlands. Interviews were conducted mostly in Tok Pisin.
      Interviews were transcribed and the data were analysed though thematic coding.
      RESULTS: Huli people use 'eating coffee candy' as a metaphor for engaging in sex
      at funerals. This is very new and against traditional values, where women
      attended funerals and men only built the coffins and buried the body. Nowadays,
      sex occurs at funerals. This change has disturbed older people because it has not
      only changed the customary meaning of the funeral space, but it has also
      encouraged the spread of HIV. Huli use the fatalistic expression 'Eat coffee
      candy and die,' to refer to funerals as a space of HIV risk. CONCLUSION: Huli
      community and church leaders, and health workers are attempting to deal with the
      situation by not allowing men to stay at the funeral site overnight, burying the
      dead on the same day they die and using customary village law to charge men
      caught having sex at a funeral. However, traditional beliefs and rapid social
      change in the context of an HIV epidemic need to be taken into account.

PMID- 22951100
TI  - Influence of angiotensin II type 1 receptor-associated protein on prenatal
      development and adult hypertension after maternal dietary protein restriction
      during pregnancy.
AB  - An adverse relationship between suboptimal fetal environments and the development
      of adult diseases, such as hypertension, type II diabetes, and cardiovascular
      disease, has been reported in numerous studies. The purpose of this study was to
      investigate the strain difference of offspring's response to maternal
      malnutrition during pregnancy and the involvement of the renin-angiotensin system
      (RAS) in the development of adult hypertension using C57BL/6J (C57) mice and
      angiotensin II (Ang II) type 1 receptor-associated protein-transgenic (ATRAP-Tg)
      mice. Pregnant dams were fed an isocaloric diet containing either 20% (normal
      protein; NP) or 8% (low protein; LP) protein. Birth weight was significantly
      reduced in C57-LP offspring, but not in ATRAP-Tg-LP offspring. Arterial blood
      pressure was higher in C57-LP offspring than in the other groups. In contrast,
      ATRAP-Tg-LP offspring did not show an increase in blood pressure compared with NP
      offspring. Renal angiotensin II type 1 (AT(1)) receptor expression was not
      altered by maternal malnutrition, whereas angiotensin II type 2 receptor
      expression was significantly decreased in C57-LP offspring. In conclusion, these
      findings suggest that a suboptimal intrauterine environment induces adult
      hypertension because of an alteration of expression of RAS components, which was
      partly suppressed by sustained ATRAP overexpression via attenuation of the AT(1)
      receptor-mediated pathological response.

PMID- 22951101
TI  - Thiazide diuretics in advanced chronic kidney disease.
AB  - Chronic kidney disease (CKD) is prevalent in 3%-4% of the adult population in the
      United States, and the vast majority of these people are hypertensive. Compared
      with those with essential hypertension, hypertension in CKD remains poorly
      controlled despite the use of multiple antihypertensive drugs. Hypervolemia is
      thought to be a major cause of hypertension, and diuretics are useful to improve
      blood pressure control in CKD. Non-osmotic storage of sodium in the skin and
      muscle may be a novel mechanism by which sodium may modulate hypertension;
      further work is need to study this novel phenomenon with diuretics. Among people
      with stage 4 CKD, loop diuretics are recommended over thiazides. Thiazide
      diuretics are deemed ineffective in people with stage 4 CKD. Review of the
      literature suggests that thiazides may be useful even among people with advanced
      CKD. They cause a negative sodium balance, increasing sodium excretion by 10%-15%
      and weight loss by 1-2 kg in observational studies. Observational data show
      improvement in seated clinic blood pressure of about 10-15 mm Hg systolic and 5
      10 mm Hg diastolic, whereas randomized trials show about 15 mm Hg improvement in
      mean arterial pressure. Volume depletion, hyponatremia, hypokalemia,
      hypercalcemia, and acute kidney injury are adverse effects that should be closely
      monitored. Our review suggests that adequately powered randomized trials are
      needed before the use of thiazide diuretics can be firmly recommended in those
      with advanced CKD.

PMID- 22951102
TI  - Quantitative analysis of sperm mRNA in the pig: relationship with early embryo
      development and capacitation.
AB  - Although it is well known that mRNA is present in mammalian spermatozoa, the
      relevance of mRNA to capacitation and early embryo development in the pig remains
      unclear. In the present study, we investigated differences in the abundance of
      selected mRNAs coding for MYC, CYP19, ADAM2, PRM1 and PRM2 in purified porcine
      spermatozoa depending on embryo cleavage rate and capacitation (n=20 semen
      samples). Semen samples were used in IVF procedures, with subsequent embryo
      development classified into one of two groups based on cleavage rate (i.e. high
      (>75%) and low (<75%) cleavage groups) and mRNA abundance in purified spermatozoa
      compared between these two groups. In addition, mRNA abundance was compared
      between capacitated and non-capacitated spermatozoa. Comparison of mRNA levels
      between porcine spermatozoa revealed that the abundance of MYC, CYP19, ADAM2,
      PRM1 and PRM2 mRNA was significantly greater in the high cleavage group (n=10
      high cleavage group semen samples) than in the low cleavage group (n=10; P<0.05).
      Significant downregulation of MYC mRNA was observed in capacitated spermatozoa
      (n=12; P<0.05). The results of the present study suggest that the amount of
      specific mRNAs could be used for estimating the quality of spermatozoa in the
      pig.

PMID- 22951103
TI  - Multifunctional near-infrared-emitting nano-conjugates based on gold clusters for
      tumor imaging and therapy.
AB  - Gold nanoclusters (NCs) were functionalized as a fluorescent probe and a pro-drug
      intended for tumor diagnosis and therapy. Firstly, Au NCs were conjugated with
      methionine (Met) and MPA, a near-infrared (NIR) fluorescent dye, giving a probe,
      Au-Met-MPA. The tumor targeting capability endowed by Met as well as low
      cytotoxicity of this contrast agent and its clinical potential for tumor
      targeting imaging were demonstrated in vitro and in vivo. Secondly, Doxorubicin
      (DOX), a widely used clinical anti-cancer drug, was immobilized on the methionine
      modified Au NCs to form a pro-drug, Au-Met-DOX. The enhanced tumor affinity and
      improved anti-tumor activity of this pro-drug were demonstrated. Results in this
      study suggest not only the prospect of non-toxic Au NCs modified with functional
      ligands for tumor-targeted imaging, but also confirm the promising future of Au
      NCs as a core for the design of pro-drug in the field of cancer therapy.

PMID- 22951104
TI  - Employing mated females as recipients for transfer of cloned dog embryos.
AB  - It has been suggested that co-transferring parthenogenetic embryos could improve
      the pregnancy success rate with cloned embryos in mammals. As an alternative to
      co-transferring parthenotes, in dogs we employed recipient females that possessed
      in vivo-fertilised embryos as a result of mating to determine whether mated
      bitches could be suitable recipients for cloned embryos. The effect of using
      mated recipients on implantation and pregnancy rates of canine somatic cell
      nuclear transfer embryos was also determined. Cloned embryos were transferred
      into the oviducts of naturally synchronous females that had mated with male dogs
      before ovulation. The pregnancy rate appeared to be similar between mated
      recipients (50%) and non-mated recipients (28.57%; P>0.05). However, the delivery
      rate of cloned pups was significantly higher in mated recipients than non-mated
      recipients (10.53 vs 2.38%; P<0.05). A decrease in progesterone levels in the
      mated recipients before the due date induced natural delivery. However, cloned
      pups in non-mated recipients were delivered by Caesarean section because the fall
      in progesterone concentration in these females did not occur until the due date.
      The present study demonstrated for the first time that mated female dogs can be
      used as recipients for cloned embryos.

PMID- 22951105
TI  - Use of health services for sexually transmitted and blood-borne viral infections
      by young Aboriginal people in New South Wales.
AB  - The objective of the present study was to describe use of health services for
      sexually transmitted infections (STI), blood borne viral infections (BBV) and
      drug and alcohol issues by young Aboriginal people in New South Wales (NSW). A
      cross-sectional survey was conducted at two Aboriginal sports and cultural events
      in NSW, in 2007 and 2008, among Aboriginal people aged 16-30 years to ascertain
      their knowledge of STI, BBV, associated risk behaviours and health service access
      in NSW. A total of 293 young Aboriginal people completed the survey; 58% were
      female, the mean age was 20 years, and almost 70% were single. Just over one
      third (34%) of participants had been tested for an STI in the past 12 months, and
      over half (58%) reported that they had ever had an STI test (including HIV). Of
      respondents who had had an STI test in the past 12 months, 54.0% had done so at
      an Aboriginal Community Controlled Health Service (ACCHS) and 29% by a GP. Just
      over one-third (36%) of participants had ever had a test for hepatitis C, 45% of
      whom had received their test at an ACCHS. Participants were also asked about the
      types of services they had used for advice about STI and BBV. Of the 69% who had
      sought STI advice, ACCHS was the most common clinical location for doing so (36%
      for STI and 26% for hepatitis C). This study highlights the important role that
      ACCHS play in the provision of STI and BBV testing care and management for a
      cohort of young Aboriginal people in NSW.

PMID- 22951106
TI  - Cryopreservation and long-term maintenance of bovine embryo-derived cell lines.
AB  - The aim of this study was to develop methods for cryopreservation and long-term
      maintenance of putative bovine embryonic stem cells (ESCs). Putative bovine ESC
      (bESC) lines (n=3) isolated in conventional medium were used to compare slow
      freezing and vitrification. After warming, vitrified cells (96.9%) demonstrated
      significantly (P<0.05) better survival than frozen-thawed cells (81.5%) and
      formed significantly more colonies with good morphology (vitrification: 93/93,
      100.0%; slow-freezing: 74/106, 69.81%; P<0.05). The effect of inhibitors of
      differentiation (PD184352, SU5402, CHIR99021) on ESC maintenance was assessed on
      putative bESC lines established in N2B27-3i medium (n=8) or conventional medium
      (n=1) after culture over 30 passages (>240 days). All cell lines expressed ALP,
      SSEA1, SSEA4, OCT4, REX1 and SSEA1. OCT4 expression was confirmed by relative
      real-time PCR and was upregulated in early passages of putative bESCs cultured in
      N2B27-3i (2.9+/-0.89-fold higher at Passage (P) 2-4), whereas the converse was
      observed later (P22-26; 2.2+/-0.1-fold increase in conventional medium). Putative
      bESC lines isolated in N2B27-3i medium (n=3) or conventional medium (n=1) were
      vitrified at P18 and, after warming, were cultured for a further 12 passages.
      These cells survived vitrification and expressed OCT4, REX1, SSEA1, ALP, SSEA1
      and SSEA4. These results demonstrate that putative bESC lines that express
      pluripotent markers can be cultured long term and retain expression of
      pluripotent markers after vitrification.

PMID- 22951107
TI  - Glutamatergic neurotransmission in the hypothalamus PVN on heart rate variability
      in exercise trained rats.
AB  - The paraventricular nucleus of hypothalamus (PVN) is a well known site of
      integration for autonomic and cardiovascular responses, and the glutamate
      neurotransmitter plays an important role. The aim of our study was to evaluate
      the cardiovascular parameters and autonomic modulation by means of spectral
      analysis after ionotropic glutamate receptor inhibition in the PVN in conscious
      sedentary (S) or swimming trained (ST) rats. After exercise training protocol,
      adult male Wistar rats, instrumented with guide cannulae to PVN and artery and
      vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR)
      recording. At baseline, physical training induced a resting bradycardia (S: 379
      +/- 3, ST: 349 +/- 2 bpm, Pb<0.05) and promoted adaptations in HRV characterized
      by an increase of HF in normalized values and a decrease of LF in absolute and
      normalized units compared with the sedentary group. Microinjection of kynurenic
      acid (KYNA) in the PVN of sedentary and trained rats promoted decreases in MAP
      and HR, but the decrease in HR was smaller in the trained animals (DeltaHRS: -48
      +/- 7, ST: -28 +/- 4 bpm, Pb<0.05). Furthermore, the differences in baseline
      parameters of pulse interval, found between sedentary and trained animals,
      disappeared after KYNA microinjection in the PVN. Our data suggest that the
      cardiovascular and autonomic adaptations to the heart induced by exercise
      training may involve glutamatergic mechanisms in the PVN.

PMID- 22951109
TI  - Coronary artery stent evaluation by combining iterative reconstruction and high
      resolution kernel at coronary CT angiography.
AB  - PURPOSE: To evaluate stent lumen visualization by combining high-resolution
      cardiac kernel and the iterative reconstruction (iDose) on an anthropomorphic
      moving heart phantom and in patients at coronary computed tomography (CT)
      angiography. MATERIALS AND METHODS: We used the moving heart phantom and a 64
      detector-row CT, retrospectively gated helical scanning, and image
      reconstruction. The heart rate was set at nonpulsating condition of 0 beats/min,
      50 beats/min, and 80 beats/min. The 120-kV images were reconstructed in
      synchronization with electrocardiogram data using filtered back projection (FBP)
      or iDose algorithm and standard kernel/filter (CB) or high-resolution
      kernel/filter (CD). We measured image noise, the kurtosis, and stent lumen
      diameter in the phantom study. We also assessed the visual inspections by two
      radiologists. RESULTS: With cardiac motion at 50 and 80 beats/min, the difference
      of kurtosis improved with CD relative to CB (P < .05). iDose algorithm with level
      7 provided lowest noise, with no statistically significance in difference of the
      kurtosis relative to level 4 (P > .05). Without cardiac motion at 0 beats/min,
      the stent lumen diameter measurements with CD kernel were better relative to CB
      kernel (P < .05). In addition, no significant difference was found in stent lumen
      diameter between iDose level 4 and level 7 (P > .05). CONCLUSION: The use of
      iDose and a sharp kernel allowed improved stent visualization at a lower
      radiation dose.

PMID- 22951108
TI  - Targeting angiogenesis in the pathological ovary.
AB  - The ovary is a key tissue in the study of physiological neo-vascularisation in
      the adult and its study has highlighted important molecules involved in the
      regulation of angiogenesis in vivo. These include vascular endothelial growth
      factor, delta-like ligand 4, thrombospondin-1, prokineticin-1 and prostaglandin
      E2. Targeting these molecular pathways has therapeutic potential and their
      manipulation has an increasing preclinical and clinical role in the management of
      the pathological ovary. Targeting angiogenic pathways has utility in the
      promotion of ovarian angiogenesis to improve tissue and follicle survival and
      function as well as the prevention and management of ovarian hyperstimulation
      syndrome. There is a theoretical possibility that targeting angiogenesis may
      improve the function of the polycystic ovary and a real role for targeting
      angiogenesis in ovarian cancer.

PMID- 22951110
TI  - Establishing a normative atlas of the human lung: computing the average
      transformation and atlas construction.
AB  - RATIONALE AND OBJECTIVES: To establish the range of normal for quantitative
      computed tomography (CT)-based measures of lung structure and function, we seek
      to develop methods for matching pulmonary structures across individuals and
      establishing a normative human lung atlas. MATERIALS AND METHODS: In our previous
      work, we have presented a three-dimensional (3D) image registration method
      suitable for pulmonary atlas construction based on CT datasets. The method has
      been applied to a population of normative lungs in multiple experiments and, in
      each instance, has resulted in significant reductions in registration errors.
      This study is a continuation to our previous work by presenting a method for
      synthesizing a computerized human lung atlas from previously registered and
      matched 3D pulmonary CT datasets from a population of normative subjects. Our
      method consists of defining the origin of the atlas coordinate system; defining
      the nomenclature and labels for anatomical structures within the atlas system;
      computing the average transformation based on the displacement fields to register
      individual subject to the common template subject; constructing the atlas by
      deforming the template with the average transformation; and calculating shape
      variations within the population. RESULTS: The feasibility of pulmonary atlas
      construction was evaluated using CT datasets from 20 normal volunteers.
      Substantial reductions in shape variability were demonstrated. In addition, the
      constructed atlas depends only slightly on a specific subject being selected as
      the template. These results indicate the framework is a robust and valid method
      for pulmonary atlas construction based on CT scans. The atlas consists of a
      grayscale CT dataset of the template, a labeled mask dataset of the template (ie,
      lungs, lobes, and lobar fissures are labeled with different gray levels), a data
      set representing the population's average shape, datasets representing the
      population's shape variations (ie, the magnitude of standard deviation), a data
      structure to contain the labels and coordinates of major airway branchpoints, and
      the labels of the mask dataset, and a reference coordinate system for each lung.
      CONCLUSION: A computerized human lung atlas representing by the average shape of
      a population of twenty normal subjects was constructed and visualized. The atlas
      provides a basis for establishing regional ranges of normative values for
      structural and functional measures of the human lung. In the future, we plan to
      use the computerized human lung atlas to help detect and quantify early signs of
      lung pathology.

PMID- 22951111
TI  - Quantitative assessment of asymmetric aortic dilation with valve-related aortic
      disease.
AB  - RATIONALE AND OBJECTIVES: Previous work suggests that ascending aortic (AsAo)
      dilation can be asymmetric and is potentially related to valve-related blood flow
      abnormalities. The aim of this study was to investigate the relationship between
      the aortic valve and AsAo dilation using a quantitative, three-dimensional
      assessment of aortic shapes. MATERIALS AND METHODS: Computed tomographic and
      magnetic resonance images of the thorax were retrospectively reviewed. Four
      groups with aortic dilation were studied: those with tricuspid aortic valves
      (TAVs) with and without stenosis and those with bicuspid aortic valves (BAVs)
      with and without stenosis. Controls had either TAVs or BAVs but no aortic
      stenosis or dilation. In additional to standard orthogonal diameters, a unique
      measurement of AsAo asymmetry was used: the ratio of the greater to lesser
      curvatures measured using three-dimensional reformats in a "candy-cane"
      orientation. RESULTS: A total of 105 patients were identified. Ratios of greater
      to lesser curvature in patients with aortic dilation and nonstenotic TAVs were
      not significantly different from those in controls (1.69 vs 1.55, P > .20), but
      the asymmetry reflected by this ratio was markedly increased in patients with
      aortic dilation and stenotic TAVs (1.94, P < .001). Patients with aortic dilation
      and BAVs had significantly elevated ratios regardless of the status of the aortic
      valve (1.96 for nonstenotic and 2.05 for stenotic vs 1.53 for controls, P <
      .001). CONCLUSIONS: Asymmetric AsAo dilation with relative bulging of the greater
      curvature is linked to aortic stenosis, but it is also seen with nonstenotic
      BAVs. This suggests that the hemodynamic forces that contribute to aortic
      dilation are not fully revealed by conventional assessment of the aortic valve.

PMID- 22951112
TI  - Usefulness of 3D DSA-MR fusion imaging in the pretreatment evaluation of brain
      arteriovenous malformations.
AB  - RATIONALE AND OBJECTIVES: For the evaluation of patients scheduled for the
      treatment of brain arteriovenous malformations (AVMs), accurate anatomical
      information is essential. The purpose of this study was to assess the usefulness
      of three-dimensional (3D) digital subtraction angiography (DSA)-magnetic
      resonance (MR) fusion imaging for the pretreatment evaluation of AVMs. MATERIALS
      AND METHODS: The study population consisted of 11 consecutive patients (7 males,
      4 females; age 10-72 years; mean 45 years) with brain AVMs. All prospectively
      underwent pretreatment MR imaging (MRI), MR angiography (MRA), and two
      dimensional (2D) and 3D DSA. The 3D DSA and MR images were semiautomatically
      fused with fusion software on a workstation. In the delineation of AVM nidus,
      feeder, drainer, and relationship between AVM and the adjacent brain structures,
      two radiologists independently evaluated MRA and MRI, three-dimensional (3D) DSA,
      and MRI, and 3D DSA-MR fusion images using a 4-point scoring system. The
      referring neurosurgeons were asked whether the information provided by 3D DSA-MR
      fusion images was helpful for treatment decisions. RESULTS: For all four items,
      the delineation was significantly better with the 3D DSA/MRI or 3D DSA-MR fusion
      images than the MRA/MRI images. Although the delineation for the nidus, feeder,
      and drainer were not significantly different between the 3D DSA/MRI and 3D DSA-MR
      fusion images, 3D DSA-MR fusion imaging were significantly better for the
      relationship between AVM and the adjacent brain structures than 3D DSA/MR imaging
      (P = .0047). The information provided by 3D DSA-MR fusion images was helpful for
      treatment decisions in all cases. CONCLUSION: 3D DSA-MR fusion images are useful
      for the pretreatment evaluation of brain AVMs.

PMID- 22951113
TI  - Whether intravenous contrast is necessary for CT diagnosis of acute appendicitis
      in adult ED patients?
AB  - RATIONALE AND OBJECTIVES: To assess the necessity of intravenous contrast medium
      for abdominopelvic computed tomography (CT) diagnosis of acute appendicitis (APP)
      among adult patients with right lower quadrant (RLQ) abdominal pain at emergency
      department (ED). MATERIALS AND METHODS: ED patients with clinical suspicion of
      APP from RLQ pain for a period of 8 months were enrolled retrospectively. Both
      pre- and postintravenous contrast-enhanced CT scans were performed for these
      patients. The visibility of vermiform appendix and specific CT findings of APP
      were recorded separately for noncontrast CT (NCT) and contrast-enhanced CT (CCT)
      images without knowledge of the patient's identity and final diagnosis. The
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy of CT diagnosis for APP were compared between the two
      groups. The ease of identifying appendix was also compared. RESULTS: Forty-two
      (42.0%) of the 100 patients (55 males, 45 females; age range, 16-90 years; mean
      age, 49.3 years) were APP. There was no significant difference for the visibility
      of appendix (94% vs. 91%; P = .589) and radiological characters between the CCT
      and NCT groups. There were significant differences between the two groups for
      sensitivity (100% vs. 90.5%; P = .036), specificity (94.8% vs. 100%; P = .038),
      PPV (93.3% vs. 100%; P = .021), NPV (100% vs. 93.5%; P = .021), but no
      significant difference for accuracy (97% vs. 96%; P = 1). The appendix was easier
      to detect on CCT than NCT images (P = .013). CONCLUSION: The diagnostic
      sensitivity of CCT was significantly better than that of NCT. Intravenous
      contrast administration could also make doctors easier in indentifying
      appendixes.

PMID- 22951114
TI  - A frozen analogue approach to aminopyridinylimidazoles leading to novel and
      promising p38 MAP kinase inhibitors.
AB  - In this study we report the design, synthesis, and biological evaluation of
      constrained aminopyridinylimidazoles as p38alpha MAP kinase inhibitors. The
      frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres
      as constrained structure analogues. The identification of the most potent
      bioisostere was followed by a further derivatization to address hydrophobic
      region II. In combination with C-2 modifications of the imidazole core, we were
      able to design highly active inhibitors on the p38alpha MAP kinase. The inhibitor
      design presented herein represents a promising and highly efficient advancement
      of recent stages of development in this class of p38 MAP kinase inhibitors. In
      combination with the highly flexible synthetic strategy, directions toward
      further investigations of complex C-5 modifications of diarylimidazoles are
      indicated.

PMID- 22951115
TI  - Osteoporosis in survivors of early life starvation.
AB  - The objective of this study was to provide evidence for the association of early
      life nutritional deprivation and adult osteoporosis, in order to suggest that a
      history of such deprivation may be an indicator of increased risk of osteoporosis
      in later life. The 'fetal programming' of a range of metabolic and cardiovascular
      disorders in adults was first proposed in the 1990s and more recently extended to
      disorders of bone metabolism. Localised famines during World War II left
      populations in whom the long-term effects of maternal, fetal and infantile
      nutritional deprivation were studied. These studies supported the original
      concept of 'fetal programming' but did not consider bone metabolism. The present
      paper offers clinical data from another cohort of World War II famine survivors -
      those from the Holocaust. The data presented here, specifically addressing the
      issue of osteoporosis, report on 11 Holocaust survivors in Australia (five
      females, six males) who were exposed to starvation in early life. The cases show,
      in addition to other metabolic disorders associated with early life starvation,
      various levels of osteoporosis, often with premature onset. The cohort studied is
      too small to support firm conclusions, but the evidence suggests that the risk of
      adult osteoporosis in both males and females is increased by severe starvation
      early in life - not just in the period from gestation to infancy but also in
      childhood and young adulthood. It is recommended that epidemiological research on
      this issue be undertaken, to assist planning for the future health needs of
      immigrants to Australia coming from famine affected backgrounds. Pending such
      research, it would be prudent for primary care health workers to be alert to the
      prima facie association between early life starvation and adult osteoporosis, and
      to take this factor into account along with other indicators when assessing a
      patient's risk of osteoporosis in later life.

PMID- 22951116
TI  - Association of the transcription profile of bovine oocytes and embryos with
      developmental potential.
AB  - Although improvements in culture system have enhanced in vitro embryo production,
      success rates are still not adequate. The reasons for developmental arrest of a
      part of in vitro produced embryos are unknown, but are connected in part with low
      cytoplasmic competence of oocytes. The immaturity of cytoplasm can negatively
      influence fertilization efficiency and subsequent progression through embryonic
      genome activation (EGA), which are necessary steps in further pre-implantation
      development. A large number of studies have compared mRNA abundance among oocytes
      with different developmental competence with the aim to find markers of the
      normal embryo development. The amount of mitochondrial DNA (mtDNA) and mRNA for
      mitochondrial transcriptional factors directing oxidative phosphorylation belongs
      to such promising markers. Nevertheless, recently published studies revealed that
      the mammalian embryo is able to compensate for a reduced level of mtDNA in oocyte
      during subsequent pre-implantation development. The search for other molecular
      markers is in progress. Characterization of oocyte and embryonic mRNA expression
      patterns during the pre-implantation period, and their relationship to the
      successful in vitro and in vivo development will be essential for defining the
      optimized culture conditions or the nuclear transfer protocols. Microarrays
      technology enables us to reveal the differentially expressed genes during EGA,
      and to compare the expression profile of in vivo and in vitro produced embryos.
      Recent evidence indicates that the depletion of the pool of stored maternal mRNAs
      is critical for subsequent embryo development. All these experiments gradually
      offer a list of possible candidates for quality and developmental competence
      markers for mammalian oocytes and pre-implantation embryos.

PMID- 22951117
TI  - Comparison between lactating and non-lactating dairy cows on follicular growth
      and corpus luteum development, and endocrine patterns of ovarian steroids and
      luteinizing hormone in the estrous cycles.
AB  - The dynamics of ovarian follicle, corpus luteum (CL), and peripheral plasma
      ovarian steroids were compared between lactating and non-lactating cows, and a
      possible association of pulsatile luteinizing hormone (LH) secretion with the
      dynamics was examined. Lactating (n=5) and non-lactating (n=5) cows were
      monitored daily for follicle and CL throughout two consecutive estrous cycles
      (Day 0: day of ovulation). Blood samples were collected daily and at 15 min
      intervals for 8h on Days 2, 4, 6, 8, and 14 of the second cycle. Lactating cows
      had larger CL (25.4 +/- 1.8mm vs. 23.5 +/- 1.5mm, P<0.01) and greater
      progesterone concentrations (4.6 +/- 1.0ng/ml vs. 3.9 +/- 0.9 ng/ml, P<0.01)
      during mid-luteal phase compared with non-lactating cows. Maximal diameters of
      the first wave dominant follicle (17.2 +/- 1.8mm vs. 15.5 +/- 0.8mm) and the
      ovulatory follicle (17.9 +/- 1.2mm vs. 15.2 +/- 0.8mm) were greater (P<0.05) in
      lactating cows than in non-lactating cows during the estrous cycles with two
      follicular waves, but no significant differences were detected between the groups
      during the estrous cycles with three follicular waves. Plasma estradiol
      concentrations did not differ between the groups throughout the experiment.
      Lactating cows had more LH pulses from Days 2 to 14 than non-lactating cows.
      These results imply that differences in ovarian dynamics may exist between
      lactating and non-lactating cows, for which the increased number of LH pulses
      observed in lactating cows may have responsibility.

PMID- 22951119
TI  - The epidemiology of anal human papillomavirus infection among women and men
      having sex with women.
AB  - The goal of this review is to summarise epidemiological data that support an
      understanding of the natural history of anal human papillomavirus (HPV) among
      women and men having sex with women (MSW). HPV is a common infection of the anal
      canal among women and MSW. Although there have been a limited number of studies
      to date, both oncogenic and nononcogenic HPV genotypes commonly occur among these
      populations even when individuals do not report receptive anal sex. Genotype
      distribution is quite diverse, with recent studies typically detecting more than
      two dozen genotypes in the anal canal in samples of women and MSW. Factors most
      consistently associated with HPV in the anal canal among both women and MSW are
      lifetime number of sexual partners and detection of HPV at the genitals. The
      common finding of genotypic concordance between the genitals and anal canal in
      women and MSW, and the infectious nature of HPV, in addition to a limited number
      of studies offering empirical evidence of anal-to-genital self-inoculation and
      evidence of HPV hand carriage, may help explain the detection of HPV in the anal
      canal outside the context of receptive anal sex. HPV vaccination has been shown
      to reduce anal HPV infection among women and is also a promising prevention
      strategy among MSW.

PMID- 22951118
TI  - Application of next generation sequencing in mammalian embryogenomics: lessons
      learned from endogenous betaretroviruses of sheep.
AB  - Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and
      are remnants of ancient exogenous retroviral infections of the host germline
      transmitted vertically from generation to generation. The sheep genome contains
      27 JSRV-related endogenous betaretroviruses (enJSRVs) related to the pathogenic
      Jaagsiekte sheep retrovirus (JSRV) that have been integrating in the host genome
      for the last 5-7 million years. The exogenous JSRV is a causative agent of a
      transmissible lung cancer in sheep, and enJSRVs are able to protect the host
      against JSRV infection. In sheep, the enJSRVs are most abundantly expressed in
      the uterine epithelia as well as in the conceptus (embryo and associated
      extraembryonic membranes) trophectoderm. Sixteen of the 27 enJSRV loci contain an
      envelope (env) gene with an intact open reading frame, and in utero loss-of
      function experiments found the enJSRVs Env to be essential for trophoblast
      outgrowth and conceptus elongation. Collectively, available evidence supports the
      ideas that genes captured from ancestral retroviruses were pivotal in the
      acquisition of new, important functions in mammalian evolution and were
      positively selected for biological roles in genome plasticity, protection of the
      host against infection of related pathogenic and exogenous retroviruses, and a
      convergent physiological role in placental morphogenesis and thus mammalian
      reproduction. The discovery of ERVs in mammals was initially based on molecular
      cloning discovery techniques and will be boosted forward by next generation
      sequencing technologies and in silico discovery techniques.

PMID- 22951120
TI  - Quantitative analysis of endocardial and epicardial left ventricular myocardial
      deformation-comparison of strain-encoded cardiac magnetic resonance imaging with
      two-dimensional speckle-tracking echocardiography.
AB  - BACKGROUND: Quantitative analysis of segmental myocardial deformation of
      different myocardial layers has become possible using strain-encoded cardiac
      magnetic resonance imaging (SENC) and speckle-tracking echocardiography (STE). We
      evaluated and compared the quantitative analysis of myocardial deformation using
      SENC and STE. METHODS: In 44 patients (age 61 +/- 13 years, 34 men), SENC by
      cardiac magnetic resonance imaging using a 1.5-Tesla whole-body scanner and two
      dimensional STE were performed prospectively. Quantitative layer-specific
      analysis of segmental left ventricular function was performed to determine the
      peak circumferential and peak longitudinal systolic strain values using SENC and
      STE of an endocardial and epicardial myocardial layer. In addition, segmental
      function was defined as normokinetic, hypokinetic, or akinetic by visual analysis
      of the magnetic resonance imaging cine sequences. RESULTS: The endocardial and
      epicardial strain defined by SENC or STE differed significantly between the
      visually defined segmental function states. The correlation of the peak
      circumferential endocardial strain by SENC versus STE (intraclass correlation
      coefficient [ICC] 0.493, 95% CI 0.358-0.597) tended to be better than the
      correlation of the circumferential epicardial strain using both methods (ICC
      0.321, 95% CI 0.238-0.399). The correlation of the peak longitudinal endocardial
      strain by SENC and STE was similar (ICC 0.472, 95% CI 0.398-0.541), in contrast
      to the longitudinal epicardial strain analysis by both techniques (ICC 0.554, 95%
      CI 0.417-0.655). Circumferential strain analysis by STE allowed better
      distinction of the hypokinetic or akinetic segments from the normokinetic
      segments than did the circumferential strain analysis by SENC of the endocardial
      layer (area under the receiver operating characteristic curve [AUC ROC] 0.946 vs
      0.884; P < .001) or epicardial layer (AUC ROC 0.884 vs 0.782; P < .001).
      Longitudinal strain analysis using STE and SENC of the endocardial layer (AUC ROC
      0.851 vs 0.839; P = .5838) and epicardial layer (AUC ROC 0.849 vs 0.833; P =
      .4321) had similar diagnostic value for identifying the presence of hypokinetic
      and akinetic segments. CONCLUSIONS: Quantitative analysis of segmental
      deformation by SENC and STE allowed accurate distinction of myocardial segments
      with different functional states. Circumferential endocardial strain analysis by
      STE allowed the best distinction of segments with impaired function from the
      normokinetic segments.

PMID- 22951121
TI  - Consideration of gender in diagnosis and management of blood-borne viruses: the
      case of hepatitis C.
AB  - Gender-sensitive health education and clinical management are key components of
      successful care for people living with chronic illness, yet there is little
      research available on the specific needs of women living with hepatitis C viral
      (HCV) infection. This paper reports on a qualitative investigation of HCV
      diagnosis, symptoms, health care and wellbeing among 109 women living with HCV in
      two major cities in Australia. Women's experiences of HCV reflect several gender
      specific needs around diagnosis, reproductive health and psycho-social wellbeing.
      Personal relationships were central to women's experiences of health and health
      care and remained dominant in their considerations for the future. Particularly
      because women are more likely than men to be responsible for family, we highlight
      the need to consider the social issues of stigma, poverty and drug use when
      caring for Australian women living with HCV. 

PMID- 22951122
TI  - A novel automated spike sorting algorithm with adaptable feature extraction.
AB  - To study the electrophysiological properties of neuronal networks, in vitro
      studies based on microelectrode arrays have become a viable tool for analysis.
      Although in constant progress, a challenging task still remains in this area: the
      development of an efficient spike sorting algorithm that allows an accurate
      signal analysis at the single-cell level. Most sorting algorithms currently
      available only extract a specific feature type, such as the principal components
      or Wavelet coefficients of the measured spike signals in order to separate
      different spike shapes generated by different neurons. However, due to the great
      variety in the obtained spike shapes, the derivation of an optimal feature set is
      still a very complex issue that current algorithms struggle with. To address this
      problem, we propose a novel algorithm that (i) extracts a variety of geometric,
      Wavelet and principal component-based features and (ii) automatically derives a
      feature subset, most suitable for sorting an individual set of spike signals.
      Thus, there is a new approach that evaluates the probability distribution of the
      obtained spike features and consequently determines the candidates most suitable
      for the actual spike sorting. These candidates can be formed into an individually
      adjusted set of spike features, allowing a separation of the various shapes
      present in the obtained neuronal signal by a subsequent expectation maximisation
      clustering algorithm. Test results with simulated data files and data obtained
      from chick embryonic neurons cultured on microelectrode arrays showed an
      excellent classification result, indicating the superior performance of the
      described algorithm approach.

PMID- 22951123
TI  - [A woman with multiple masses on her left hand].
AB  - We describe a 66-year-old woman who presented with firm masses on her left hand,
      which had recently increased in size, and multiple haemangiomas. A diagnosis of
      Maffucci syndrome was established. Renewed growth of enchondromas during
      adulthood is suspicious for malignant transformation. Therefore, curettage with
      adjuvant fenolisation was performed in our patient. Clinical and radiological
      follow-up was required concerning local recurrence.

PMID- 22951124
TI  - [Topical treatment of vulvar lichen sclerosus with calcineurin inhibitors].
AB  - OBJECTIVE: To provide an overview of the literature concerning the topical
      treatment of vulvar lichen sclerosus, a chronic inflammatory skin disease, with
      calcineurin inhibitors, such as pimecrolimus and tacrolimus. DESIGN: A literature
      review into the use of topical calcineurin inhibitors (TCIs) in the treatment of
      vulvar lichen sclerosus. METHOD: A literature search was performed using PubMed
      and EMBASE and the search terms 'tacrolimus', 'pimecrolimus' or 'calcineurin
      inhibitors' and 'lichen sclerosus et atrophicus', 'vulvar lichen sclerosus',
      'vulvar dermatoses' or 'vulvar diseases'. RESULTS: The search produced 6 case
      reports, 5 patient series, 3 pilot studies, 2 open-label studies and 1 RCT
      concerning the use of TCIs for the treatment of vulvar lichen sclerosus. The
      literature shows that both medications are effective and well tolerated. However,
      glucocorticoids seem to be effective in more patients than TCIs. Tacrolimus has a
      stronger immunosuppressant effect than pimecrolimus and therefore seems to be
      more effective without having more observed side-effects. CONCLUSIONS: TCIs may
      represent a useful second-line therapeutic option for patients for whom treatment
      with glucocorticoids is not effective or who do not tolerate them well.
      Randomized clinical studies are required to determine the role of TCIs in the
      treatment of lichen sclerosus. CONFLICT OF INTEREST: none declared. Financial
      support: none declared.

PMID- 22951125
TI  - [A woman with retrograde amnesia].
AB  - A 56-year-old woman presented with retrograde amnesia and confusion at the
      Emergency Department after falling down the stairs. Physical examination revealed
      a bilateral periorbital hematoma (raccoon eyes) and bilateral retroauricular
      ecchymosis, both strongly indicative of a basilar skull fracture.

PMID- 22951126
TI  - [Reproduction in the year 2012: in vivo or in vitro?].
AB  - The Dutch Minister of Health has proposed reducing the number of reimbursed in
      vitro fertilisation (IVF) cycles per couple from 3 to 1, in order to save 30
      million euro per year. In the Netherlands, the number of IVF cycles has increased
      by 50% in the past 13 years, resulting in, on average, one child conceived
      through IVF in every classroom today. The increase in the number of IVF
      treatments is also caused by expansion of the indications for IVF, despite the
      lack of evidence proving the effectiveness of IVF for some of these indications.
      In a time of financial constraint, the restriction of reimbursed indications
      would be fairer than reducing the number of reimbursed treatments with IVF or
      intracytoplasmic sperm injection (ICSI) for all couples.

PMID- 22951128
TI  - [Outcome of an intestinal rehabilitation program for children with short bowel
      syndrome].
AB  - OBJECTIVE: To evaluate an intestinal rehabilitation program, introduced in 2001,
      for children who developed short bowel syndrome (SBS) after extensive intestinal
      resection. DESIGN: Retrospective cohort study. METHOD: General information on
      disease status and outcome of intestinal rehabilitation plus demographic data on
      all SBS patients, treated in the programme between 2001 and 2009, were collected.
      The outcome measures were intestinal autonomy, intestinal and/or liver
      transplantation and survival. RESULTS: A total of 10 boys and 9 girls, born at a
      median gestational age of 36 weeks, were treated according to intestinal
      rehabilitation programme guidelines. Eight of them had been referred to our
      centre from elsewhere, 3 times as many as in 1991-2000. The causes of SBS were:
      intestinal atresia (n = 3), gastroschisis (n = 2), volvulus (n = 9), necrotising
      enterocolitis (n = 3) or strangulation (n = 2). Median remaining small-intestinal
      length was 35 cm (range: 10-70 cm). In 14 patients the ileocecal valve was still
      present and in all 19 patients at least 25% of the colon remained. The median
      follow-up period was 25 months (range: 50 days-9 years). Following total
      parenteral nutrition lasting a median 138 days (range: 41 days-11 years), 16
      patients (84%) reached intestinal autonomy. Central venous catheter-related
      complications occurred in all of the patients; liver function disorders in 13
      (68%) and failure to thrive in 5 (26%). One patient underwent an intestinal
      lengthening procedure. None of the patients needed an intestinal transplantation,
      but one patient underwent a liver transplantation for intestinal failure
      associated liver disease. Overall mortality was 11%: 2 patients died of abdominal
      sepsis. CONCLUSION: The specialised intestinal rehabilitation programme led to
      intestinal autonomy in 84% of the patients with SBS.

PMID- 22951129
TI  - [Catheter-directed thrombolysis in iliofemoral deep-vein thrombosis].
AB  - Despite optimal treatment of acute deep-vein thrombosis (DVT) there is a great
      chance of recurrent DVT and development of post-thrombotic syndrome (PTS) in the
      long term. The degree of spontaneous recanalization differs per patient and per
      thrombus location. 90% of all femoropopliteal occlusions will fully recanalize
      within 1 year; however, in the case of an iliofemoral thrombosis, recanalization
      occurs only in a minority of cases. Post-thrombotic complications occur more
      often following iliofemoral thrombosis, and the chance of recurrent thrombosis is
      greater than following thrombosis in a more distal location. An anatomical
      variation or abnormality also more often underlies an iliofemoral thrombosis. It
      is important to identify patients with a greater chance of developing PTS
      promptly and to treat them in order to prevent post-thrombotic damage. There are
      still insufficient trial data available to implement catheter-directed
      thrombolysis as standard therapy for iliofemoral thrombosis

PMID- 22951130
TI  - [Guideline 'Incontinence urine and feces' of the Dutch Preventive Youth Health
      Care].
AB  - Continence problems can occur during childhood. This guideline is for the Dutch
      Youth Health Care (JGZ) and gives recommendations for the prevention, early
      detection and treatment of these problems. As a preventative measure advices for
      potty training should be started in children aged 18-24 months. If incontinence
      is present, it is important to take a history and carry out physical examination.
      In children over the age of 5 who are incontinent of urine the following are
      recommended: taking child out of bed, calendar with reward system, bedwetting
      alarm or voiding diary; children over the age of 8 can follow dry bed training.
      Faecal incontinence is often associated with constipation. Incontinent children
      with constipation are given advice about normal eating and exercise patterns. If
      this is not successful then laxatives are prescribed. The JGZ should refer
      further if there are indications of an underlying condition; if children over the
      age of 5 are wet during the day; if children are incontinent of faeces at night;
      if children are incontinent of faeces but not constipated; if children
      persistently wet the bed; if there is faecal incontinence despite counselling,
      and if medication needs to be prescribed.

PMID- 22951131
TI  - [Living with a short bowel: longer and better?].
AB  - Congenital malformations or complications of premature birth may require
      extensive intestinal resection which could result in short bowel syndrome.
      Prolonged parenteral nutrition and its complications (e.g. cholestasis, venous
      catheter-associated infections, thrombosis and limited vascular access) have a
      major impact on the quality of life of infants and comprise a great burden for
      parents. The merits of extensive intestinal resection are discussed from the
      perspective of a Dutch intestinal rehabilitation programme that provides
      multidisciplinary medical care and advanced surgical options, including liver and
      intestinal transplantation.

PMID- 22951132
TI  - [Decompression illness: minor symptoms, major consequences].
AB  - Nowadays, diving is being performed ever more frequently; it is thus important to
      take diving injuries into consideration in patients presenting with even minor
      complaints after diving. Every dive is risky and could result in decompression
      illness, barotrauma and/or death. We report on two cases of decompression
      illness: a 30-year old man, an occupational diver, and a 46-year old man, an
      experienced diver, who were both clinically suspected of having decompression
      illness and were treated with hyperbaric oxygen in a recompression chamber. Both
      were eventually symptom-free after several treatments. Decompression illness is
      caused by a reduction in ambient pressure, which results in intra- or
      extravascular bubbles. Symptoms vary and are dependent on the site affected: from
      minor pain to neurological symptoms and death. If patients are suspected of
      having diving injuries, we recommend contacting a centre specialised in diving
      and hyperbaric medicine. Recompression in a hyperbaric chamber is the definitive
      treatment for decompression illness and should be performed as soon as possible.

PMID- 22951133
TI  - [The bioresorbable coronary scaffold].
AB  - The routine placement of permanent metal stents has led to an improvement of the
      long-term and short-term effects of percutaneous coronary interventions.
      Treatment with the newest generation of drug-eluting stents results in a low risk
      of restenosis. The antiproliferative drug eluted by these stents, however,
      prevents endothelialisation; this leads to an increased risk of exposed metallic
      stent parts, which in turn leads to a higher risk of stent thrombosis. There is
      evidence that the vessel wall support provided by the stent is only a temporary
      requirement. Permanent metallic stents could, therefore, be superfluous in the
      long term. A bioresorbable vascular scaffold (BVS), manufactured from polylactic
      acid and completely resorbed within 18-24 months, is a new alternative. It is
      expected that these scaffolds will lead to the disappearance of the risk of late
      stent thrombosis. Theoretically, the bioresorbable vascular scaffold also
      provides a considerable advantage for patients who will probably have to undergo
      further coronary intervention in the future. Metal stents can be an important
      limiting factor for these patients.

PMID- 22951134
TI  - [Summary of the multidisciplinary guideline on cardiovascular risk management
      (revision 2011)].
AB  - The decision whether to treat individuals not previously known to have
      cardiovascular disease is based on a new risk table in which Dutch research data
      on morbidity have been incorporated. An explanation of the roles of additional
      risk factors ignored in the cardiovascular risk function, such as a sedentary
      lifestyle and a high BMI, is provided. A method for estimating the cardiovascular
      risk in patients with diabetes mellitus and rheumatoid arthritis has been
      developed. New recommendations concerning the measurement of blood pressure at
      home and in the ambulatory setting have been formulated. The recommendations for
      the choice of antihypertensive drugs have been revised. The recommendations on
      handling therapy-resistant hypertension are provided. Recommendations for
      choosing statins based on a current cost-effectiveness analysis are provided.

PMID- 22951135
TI  - [Dutch guideline for cardiovascular risk management: a consensus model].
AB  - This commentary concerns two major aspects of the guideline, which was revised in
      2011 and seems to us the result of a consensus model. The first aspect, namely,
      of age in relation to cardiovascular risk stratification and the indication that
      recent studies show that treatment of hypertension of both very old and young
      people should be considered, is discussed. The second aspect discussed in this
      commentary, regarding hyperlipidaemia in obesity and diabetes, concerns the
      argument that apolipoprotein B-100 level or non-HDL cholesterol should
      specifically be measured for screening and treatment targets.

PMID- 22951136
TI  - [The guideline 'Cardiovascular risk management' is too simplified for elderly
      care].
AB  - In the 2011 revision of the multidisciplinary guideline 'Cardiovascular Risk
      Management', the new age category '70-year olds' was added to the risk chart.
      Virtually all people aged 70 years and over have a 10-year risk of cardiovascular
      mortality and morbidity that exceeds 20%, and are therefore eligible for
      preventive medication when lifestyle changes fail. In view of the attenuating
      predictive value of classic risk factors with age, the authors of this commentary
      discuss the lack of a more age-differentiated approach for older persons. They
      underline the importance of including differences in the levels of vulnerability
      in older patients when making medication decisions. The risk of undue
      medicalisation of a large segment of the population is discussed. Alternative
      approaches are conveyed: the use of age-dependent thresholds for different risk
      categories, the use of relative risk charts, and the search for better risk
      markers in (very) old age.

PMID- 22951137
TI  - A high-throughput colorimetric-assay for monitoring glucose consumption by
      cultured trophoblast cells and placental tissue.
AB  - Diabetes mellitus is associated with abnormalities in placental structure and
      function and significant pregnancy complications. In vitro studies to investigate
      the effect of hyperglycaemia on trophoblast structure and function require an
      accurate, inexpensive and reliable assay to monitor the concentration of glucose
      in culture medium. We have modified and validated an existing protocol for use
      with a 96-well microplate. This provides a specific, high-throughput assay which
      accurately measures culture media glucose concentrations between 7 and 30 mM,
      without spectral interferences by phenol red or sera. Use of this assay revealed
      that the concentration of glucose in BeWo cell cultures remains stable for 48 h.
      In contrast placental explants rapidly consume glucose thus the concentration in
      culture media significantly decreases over 12 h necessitating more frequent
      replenishment in order to maintain the desired concentration. We therefore advise
      researchers to monitor glucose concentrations in in vitro investigations
      modelling the effect of diabetes mellitus on placental structure and function.

PMID- 22951138
TI  - The golden age of DNA metasystematics.
AB  - The convergence of next-generation sequencing and DNA barcoding has sparked a
      golden age of 'DNA metasystematics', allowing researchers to understand the
      biodiversity of an entire ecosystem solely through DNA information, and
      transforming the way we view the living world around us.

PMID- 22951139
TI  - Causes and consequences of ribonucleotide incorporation into nuclear DNA.
AB  - Intuitively one would not expect that ribonucleotides are incorporated into
      nuclear DNA beyond their role in priming Okazaki fragments, nor that such
      incorporation would be functional. However, several recent studies have shown
      that not only are ribonucleotides present in the nuclear DNA, but that they can
      be incorporated by at least two different mechanisms: random 'mis'-incorporation
      of ribonucleotides, which occurs at a surprisingly high frequency; and site
      specific incorporation at a stalled fork. Importantly, in the latter case, the
      ribonucleotides have been shown to have a biological function - acting to
      initiate a replication-coupled recombination event mediating a cell type change.
      Traditionally, it has been thought that 'random' ribonucleotide incorporation
      causes genetic instability, but new evidence suggests there may be a fine balance
      between mechanisms preventing and incorporating ribonucleotides into genomic DNA.
      Indeed, genomic ribonucleotides might have diverse roles affecting genetic
      stability, DNA damage repair, heterochromatin formation, cellular
      differentiation, and development.

PMID- 22951140
TI  - The genetics of politics: discovery, challenges, and progress.
AB  - For the greater part of human history, political behaviors, values, preferences,
      and institutions have been viewed as socially determined. Discoveries during the
      1970s that identified genetic influences on political orientations remained
      unaddressed. However, over the past decade, an unprecedented amount of
      scholarship utilizing genetic models to expand the understanding of political
      traits has emerged. Here, we review the 'genetics of politics', focusing on the
      topics that have received the most attention: attitudes, ideologies, and pro
      social political traits, including voting behavior and participation. The
      emergence of this research has sparked a broad paradigm shift in the study of
      political behaviors toward the inclusion of biological influences and recognition
      of the mutual co-dependence between genes and environment in forming political
      behaviors.

PMID- 22951141
TI  - Mouse oocyte meiosis is disturbed by knockdown of Suv4-20h.
AB  - Suv4-20h was initially characterised as a histone methyltransferase (HMTase) that
      catalyses lysine 20 of histone H4 dimethylation (H4K20me2) and trimethylation
      (H4K20me3). In the present study, using RNA interference (RNAi), we found that
      Suv4-20h activity is required for the fidelity of chromosome distribution during
      meiosis in the mammalian oocyte. Knockdown of Suv4-20h resulted in attenuation of
      H4K20me3 and the accumulation of H4K20me1. After Suv4-20h knockdown, oocytes
      exhibited an increasing percentage of aberrant chromosome alignment in MI,
      together with a decreasing percentage of polar body I extrusion. We conclude that
      Suv4-20h may be required for normal chromosome behaviour and that it is crucial
      for proper meiotic progression in mammalian oocytes.

PMID- 22951142
TI  - Effects of lipid polarisation on survival of in vivo-derived porcine zygotes
      vitrified by the superfine open pulled-straw method.
AB  - This study aimed to evaluate the post-warming in vitro viability of intact
      porcine zygotes vitrified using the superfine open pulled-straw (SOPS) method and
      to investigate whether cryotolerance is increased by lipid polarisation before
      vitrification. In vivo-derived zygotes (n=317) were either untreated before SOPS
      vitrification or subjected to one of the following pre-treatments: (1)
      centrifugation (20 min, 15000 g) or (2) equilibration in high-osmolality medium
      (6 min, 400 mOsm kg(-1)) followed by centrifugation. Vitrified-warmed and non
      vitrified fresh zygotes were cultured in vitro for 120 h. There were no
      differences in the blastocyst formation rates between the vitrification groups
      (from 35.4+/-5.3% to 48.2+/-5.6%), but fresh zygotes exhibited higher (P<0.001)
      blastocyst formation rates (87.5+/-5.3%) than did vitrified-warmed zygotes. The
      total blastocyst cell number was similar among all groups (from 34.9+/-2.8 to
      44.1+/-2.8). In conclusion, SOPS vitrification is a promising method for the
      cryopreservation of untreated in vivo-derived porcine zygotes. Neither lipid
      polarisation by centrifugation nor exposure to a high-osmolality medium followed
      by centrifugation affected the post-warming in vitro viability of zygotes. Our
      study also demonstrated that the donor is an important factor in determining the
      success of vitrification for in vivo-derived porcine zygotes.

PMID- 22951143
TI  - Primary intraosseous myoepithelioma of the mandible with ameloblastomalike
      features.
AB  - Primary intraosseous salivary gland tumors of the jaw are overwhelmingly
      malignant. We describe, for the first time, a genuine myoepithelioma originating
      centrally in the mandible. A 33-year-old man had a well-circumscribed, unilocular
      osteolytic lesion between the roots of the mandibular second premolar and first
      molar with no extraosseous extension. Histologically, an encapsulated,
      solid/trabecular tumor was composed of benign epithelioid > spindled > basaloid >
      plasmacytoid cells and showed a distinctive myoepithelial immunoprofile. Multiple
      sections revealed neither duct formation nor myxochondroid stroma. In addition,
      focal areas shared features with conventional ameloblastoma histologically and
      immunohistochemically. This unique biphenotypic cellular and architectural make
      up indicates the possibility of divergent myoepithelial and ameloblastic
      differentiation in the present jawbone tumor.

PMID- 22951144
TI  - GLP-2 receptors in human disease: high expression in gastrointestinal stromal
      tumors and Crohn's disease.
AB  - Peptide hormones of the glucagon-like peptide (GLP) family play an increasing
      clinical role, as reported for GLP-1 in diabetes therapy and insulinoma
      diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal
      actions translated into preliminary clinical studies using the GLP-2 analogue
      teduglutide for treatment of short bowel syndrome and Crohn's disease, remains
      poorly characterized in terms of expression of its receptor in tissues of
      interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and
      148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2
      receptor expression was present in 68% of gastrointestinal stromal tumors (GIST).
      Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus,
      with significant up-regulation in active Crohn's disease. The GLP-2 receptors in
      GIST may be used for clinical applications like in vivo targeting with
      radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over
      expressed GLP-2 receptor in the myenteric plexus may represent the morphological
      correlate of the clinical target of teduglutide in Crohn's disease.

PMID- 22951145
TI  - What factors contribute most to the retention of general practitioners in rural
      and remote areas?
AB  - The objectives of this study were to measure the relative strength, significance
      and contribution of factors associated with rural and remote medical workforce
      retention. Length of stay data from two Australian GP workforce datasets, the
      2008 National Minimum Data Set (4223 GPs) and a subset of the 2008 Medicine in
      Australia: Balancing Employment and Life dataset (1189 GPs), were separately
      analysed using multiple linear regression models and the results compared. Length
      of employment in their current practice location was the outcome measure.
      Consistent results were obtained across both datasets. The most important factors
      associated with the retention of rural and remote GPs, after adjusting for GP
      age, were primary income source, registrar status, hospital work and restrictions
      on practice location (which are linked to geographic location). Practice
      ownership was associated with -70% higher retention than average, whilst
      undertaking hospital work in addition to routine general practice was associated
      with at least 18% higher retention compared with if no hospital work was
      undertaken. Less important factors included geographic location, procedural
      skills, annual leave, workload and practice size. Our findings quantify a range
      of financial and economic, professional and organisational, and geographic
      factors contributing to the retention of rural GPs. These findings have important
      implications for future medical workforce policy, providing an empirical evidence
      base to support the targeting and 'bundling' of retention initiatives in order to
      optimise the retention of rural GPs.

PMID- 22951146
TI  - Clinical and genetic features of protein C deficiency in 23 unrelated Chinese
      patients.
AB  - In this study, we investigated the clinical and genetic features of protein C
      deficiency in the Chinese population. A total of 23 symptomatic patients with
      protein C deficiency were identified by thrombophilic assays. Detailed clinical
      data about the patients with respect to their personal and family history of
      venous thromboembolism (VTE) were collected. Mutational analysis was then
      performed by direct sequencing of the protein C gene (PROC) in the patients and
      their family members. Of the 23 patients, 30.4% (7/23) had additional risk
      factors, 51.2% (12/23) suffered from recurrent thrombotic episodes, and 50.0%
      (6/12) of the patients with recurrent thrombosis had more than one heterozygous
      mutation in PROC itself or combined with protein S gene (PROS). The sex
      distribution of male:female was 19:4 in the 23 symptomatic patients and 10:2 in
      the 12 recurrent patients. Almost all patients (22/23) had lower extremity deep
      vein thrombosis (DVT) and one had pulmonary embolism (PE) only. A total of 15
      different causative mutations were identified from the 23 subjects with 6 (40.0%)
      of the mutations being novel. Among the mutations identified, the Arg147Trp
      substitution was hotspot mutation in the Chinese population with a high frequency
      of 43.5%. Our finding suggests that complex genotypes of PROC or combined with
      protein S deficiency are primarily responsible for an increased risk of recurrent
      VTE. Our data further provides a framework for correlating the clinical
      pathogenesis of protein C deficiency to ethnic backgrounds in the Chinese
      population.

PMID- 22951147
TI  - Associations between family history of cardiovascular disease, knowledge of
      cardiovascular disease risk factors and health behaviours.
AB  - The objective of the study was to examine associations between family history of
      premature cardiovascular disease (CVD), knowledge of CVD risk and protective
      factors, and health behaviours. The design was via administration of a
      questionnaire to 307 participants from four general practice centre waiting rooms
      in the Sydney West area. The most recognised CVD risk factor was smoking (97.7%)
      and the most recognised CVD protective factor was omega-3 fatty acids (78.5%).
      After adjustment for age, sex, education attainment and personal history of CVD,
      a strong family history of premature CVD was associated with being more likely to
      interpret a blood pressure of 130/85 as a CVD risk factor (OR 2.77, 95% CI 1.07
      7.14), but less likely to identify being an ex-smoker (compared with never having
      smoked before) as a risk factor (OR 0.32, 95% CI 0.12-0.90). Those with a strong
      family history of premature CVD, on average, had smoked 0.82 pack years more than
      those with an average family history of premature CVD (s.e. 4.22, P=0.04). In
      conclusion, there continues to be both strengths and deficits in the community's
      overall knowledge of CVD risk and protective factors, and a strong family history
      of premature CVD appears to be an independent risk factor for smoking. 

PMID- 22951148
TI  - Daily prolactin pulse inhibits the corpus luteum during lactational quiescence in
      the marsupial, Macropus eugenii.
AB  - The corpus luteum (CL) of the tammar wallaby is inhibited by prolactin during
      lactation and seasonal quiescence. In seasonal quiescence a daily transient pulse
      of prolactin (PRL) of less than 2h duration is sufficient to maintain inhibition.
      We investigated whether the same inhibition applies in lactation and, if so, how.
      Our results show that inhibition of the CL during lactation is maintained by a
      transient pulse of prolactin once a day. They also show that the minimum time
      without a PRL pulse for the CL to escape inhibition is more than 48 h and less
      than 72 h. Nevertheless, some animals had a longer refractory period than 72 h,
      which was reflected in a longer interval to the progesterone peak and birth.
      These results support the previous conclusion that PRL exercises its effect on a
      rate-limiting step in progesterone synthesis and secretion rate from the CL,
      which precedes any increase in its mass. Therefore, we conclude that the role of
      PRL is to act as a luteostatic agent, an effect that is in marked contrast to its
      luteotrophic effect in many eutherian species, including rodents.

PMID- 22951149
TI  - A cross-sectional study of elderly Asian and European women with primary operable
      breast cancer aged 70 and older. Are there differences?
AB  - BACKGROUND: Breast cancer (BC) is becoming a disease of the elderly.
      Additionally, BC-incidence is rising in Asia. The aim of this study was to
      explore clinico-pathological characteristics and differences of breast cancer in
      elderly Asian/Han-Chinese compared to Caucasian/Austrian women. METHODS: A total
      number of 630 consecutive primary operable, unilateral breast cancer cases, 70
      years and older, were analyzed. Histo-pathological findings and biological
      characteristics of 198 Caucasian/Austrian were compared with 432 Asian/Han
      Chinese. Pearson's chi-square test was used to assess differences in the analyzed
      populations. RESULTS: A significantly higher rate of triple-negative BC (p=0.027)
      was diagnosed among the Chinese geriatric population. More estrogen-receptor
      positive BC was detected in the Caucasian study group (p<0.001). No statistically
      significant differences were detected based on tumor size, axillary lymph-node
      status, nor HER2-receptor expression. CONCLUSION: This study will help us gain
      additional ethnic-specific insight into the biological characteristics of breast
      cancer in the elderly Caucasian/Austrian and Asian/Han-Chinese populations.

PMID- 22951150
TI  - Age-related change in kidney function, its influencing factors, and association
      with asymptomatic carotid atherosclerosis in healthy individuals--a 5-year follow
      up study.
AB  - OBJECTIVES: To better define the longitudinal changes in renal function, to
      examine the associated risk factors, and to investigate whether there is an
      independent association of decline in renal function with presence of carotid
      plaque in a middle-aged and elderly healthy population. METHODS: 245 healthy
      individuals (98 males, 147 females) evaluated at baseline and 5 years later.
      RESULTS: Over five years, estimated glomerular filtration rate (eGFR) decreased
      from 98.1+/-15.6 to 90.4+/-17.3mL/min/1.73m(2). There are three kinds of change
      in eGFR (elevated, stable and decreased) during follow-up, accounting for 14%,
      29% and 57%, respectively. Multivariate analysis of cross-sectional data showed
      that gender, age, and serum uric acid (UA) were major factors which consistently
      affected eGFR at both baseline and follow-up, and that higher systolic blood
      pressure (SBP) and presence of plaque were involved in lower eGFR at the follow
      up point. In longitudinal analysis, five baseline factors - age, SBP, low-density
      lipoprotein cholesterol (LDL-C), serum transferrin (TRF) and eGFR - independently
      predicted a greater variability in renal function. In addition, presence of
      plaque was an independent risk factor for a faster decline of eGFR. CONCLUSIONS:
      Cross-sectional analysis demonstrates that renal function declines with
      increasing age. However, 43% of participants did not experience a decline in eGFR
      during follow-up. Besides older age and higher initial eGFR, presence of
      atherosclerotic carotid plaque, higher SBP, higher LDL-C and lower TRF are
      independent risk factors to predict a rapid decline of renal function in the
      healthy Chinese population.

PMID- 22951151
TI  - Geographical clustering of anal cancer incidence in Australia.
AB  - INTRODUCTION: Homosexual men are at an increased risk of anal cancer. We aimed to
      establish the burden of anal squamous cell carcinoma (SCC) in those parts of
      Australia where homosexual men are most likely to live. METHODS: Data on the
      proportion of homosexual male residents were obtained from published estimates.
      Men were categorised into three postcode groups by prevalence of men reporting
      homosexual identity. Male population data in age groups were extracted for each
      postcode group and analyses of cancer incidence were performed by postcode group.
      The analyses were restricted to 2000-2005. RESULTS: Eight postcodes had
      populations where more than 10% of males reported homosexual identity (high
      prevalence) and 4-10% of men reported homosexual activity in a further 19
      postcodes (medium prevalence). From 2000 to 2005, the average annual age
      standardised incidence rates of anal SCC in males was 7.61 per 100000 (95%
      confidence interval (CI): 4.68-10.55) and 2.21 per 100000 (95% CI: 1.05-3.37) in
      high and medium prevalence postcodes, respectively. The corresponding incidence
      rate ratios compared with low prevalence postcodes (less than 4% of males
      reported homosexual identity) were 9.6 (95% CI: 6.6-14.1) for the high prevalence
      and 2.4 (95% CI: 1.4-4.1) for the medium prevalence postcodes. CONCLUSION: A
      substantial concentration of the burden of anal cancer occurred among areas where
      large proportions of homosexual men reside. These results should guide the
      prioritisation of health service investment in anal cancer treatment and
      prevention to appropriate geographical areas.

PMID- 22951152
TI  - Benefits and risks from the national strategy for improvement of iodine
      nutrition: a community-based epidemiologic survey in Chinese schoolchildren.
AB  - OBJECTIVE: Mild to severe iodine deficiency has been documented in China since
      1960. To eliminate this persisting iodine deficiency, legislation on universal
      salt iodization was introduced in 1995 as a long-term public health intervention
      strategy. We examined the urinary iodine excretion and the iodine content of
      drinking water and salt samples to assess the benefits and risks of this national
      strategy. METHODS: We examined the urinary iodine excretion of 1594
      schoolchildren 8 to 10 y old from the 16 counties of China. The iodine content of
      1097 drinking water and 4501 table salt samples also was assessed in these
      counties. The study was conducted from April 2009 through October 2010. Urinary
      iodine excretion and iodine levels in drinking water and table salt samples were
      measured based on the Sandell-Kolthoff reaction. Data were interpreted according
      to World Health Organization criteria. RESULTS: The median urinary iodine levels
      of the schoolchildren were 198.2, 277.2, 336.2, and 494.8 MUg/L in areas with
      iodine levels lower than 10, 10 to 150, 150 to 300, and higher than 300 MUg/L in
      the drinking water, respectively. The mean iodine level in the table salt
      specimens was 30.4 mg/kg, the coverage rate was 98.6%, and the qualified rate was
      96.7%. The goiter prevalence was 8.0% in the areas with an iodine level higher
      than 150 MUg/L in the drinking water. CONCLUSION: In each area, the median
      urinary iodine of schoolchildren was nearly or above 200 MUg/L, which confirmed
      the effectiveness of the iodization strategy. However, in areas with an iodine
      content higher than 150 MUg/L in the drinking water, the schoolchildren had more
      than adequate or excessive iodine intake, which was associated with the
      prevalence of goiter. Therefore, it is important to adjust the strategy of
      universal salt iodization control in China.

PMID- 22951153
TI  - Decreased interferon-alpha and interferon-beta production in obesity and
      expression of suppressor of cytokine signaling.
AB  - OBJECTIVE: We analyzed the interferon-alpha (IFN-alpha), IFN-beta, and
      proinflammatory responses induced by Toll-like receptor (TLR) ligands in
      peripheral blood mononuclear cells (PBMCs) from obese subjects and their
      association with suppressor of cytokine signaling-1 (SOCS1) and SOCS3 expression.
      METHODS: The IFN responses were measured by real-time quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent
      assay in PBMCs stimulated with TLR-3 and TLR-7 ligands from 30 non-obese (body
      mass index <= 25 kg/m(2)) and 30 obese (body mass index >= 30 kg/m(2))
      volunteers. The mRNA expression of nuclear factor-kappaB, SOCS1, and SOCS3 also
      was evaluated by qRT-PCR. Proinflammatory cytokine responses were measured by
      enzyme-linked immunosorbent assay. RESULTS: Obese subjects showed a decreased
      ability to produce IFN-alpha and IFN-beta in response to TLR ligands; this
      response was associated with increased basal levels of SOCS3 but not SOCS1.
      However, after stimulation, the expression of SOCS3 and SOCS1 mRNA was
      significantly lower in PBMCs from obese compared with non-obese subjects. The
      PBMCs from obese subjects also showed higher basal levels of interleukin-6 and a
      decreased response of proinflammatory cytokines interleukin-6 and interleukin
      1beta after stimulation with the TLR-3 ligand compared with PBMCs from non-obese
      participants. CONCLUSION: These data suggest that obesity is related to impaired
      IFN-alpha and IFN-beta responses and increased SOCS3 basal mRNA expression and
      that a signaling pathway by TLR-3 may be involved. These results could explain,
      at least in part, the inadequate response of obese people against viral
      infections, such as influenza.

PMID- 22951154
TI  - Beneficial effects of coffee consumption go beyond antioxidation.

PMID- 22951155
TI  - Sleep deprivation is associated with lower diet quality indices and higher rate
      of general and central obesity among young female students in Iran.
AB  - OBJECTIVES: Short sleep duration and low diet quality are associated with weight
      gain. However, little is known about the relationship between sleep duration and
      the quality of diets. Therefore, we aimed to compare the diet quality indices and
      anthropometric measures between short and longer sleepers. METHODS: This cross
      sectional study consisted of 410 female youths who were chosen among students of
      Isfahan University of Medical Sciences based on stratified random sampling
      method. Dietary intake assessment was done using a semiquantitative validated
      food frequency questionnaire. Sleep duration was estimated using self-reported
      nocturnal sleep duration by each person. Anthropometric measures were done using
      standard protocols. Diet quality indices (including dietary energy density,
      dietary diversity scores, healthy eating index, nutrient adequacy ratio, and mean
      adequacy ratio) were calculated using the standard definition. RESULTS: Subjects
      who slept less than 6 h/d were more likely to be overweight and obese (P =
      0.0001) and also abdominally obese (P = 0.03). They also consumed more dietary
      energy (2406 +/- 825 versus 2092 +/- 700 kcal/d; P = 0.01, respectively) and
      carbohydrates (58.1 +/- 16.2% versus 51.6 +/- 10.3%; P = 0.03) but a lower amount
      of fiber (12 +/- 7 versus 18 +/- 7 g/d; P = 0.04), fruits (2.4 +/- 0.6 versus 3.1
      +/- 0.7 servings/d; P = 0.04), whole grains (0.9 +/- 0.1 versus 1.3 +/- 0.1
      servings/d; P = 0.04), and beans (0.3 +/- 0.1 versus 0.8 +/- 0.1 servings/d; P =
      0.04). All diet quality indices were significantly lower among short sleepers (P
      < 0.05), apart from dietary energy density, which did not differ significantly (P
      = 0.8). CONCLUSION: Our findings confirm the association of short sleep duration
      and obesity in young female youths. It might be derived from lower diet quality
      among short sleepers more than longer sleepers.

PMID- 22951156
TI  - Mechanisms responsible for disuse muscle atrophy: potential role of protein
      provision and exercise as countermeasures.
AB  - Muscle disuse is often observed after injury or during periods of illness,
      resulting in the loss of muscle mass and strength, with sometimes debilitating
      consequences. Although substantial advancements have been made in determining the
      mechanisms responsible for the etiology of muscle disuse atrophy in rodents, only
      in recent years have studies of any significant number focused on reaffirming
      these findings in humans. In this review, we discuss the processes responsible
      for disuse atrophy as based on current evidence and highlight where gaps in our
      knowledge persist. Furthermore, given the emphasis placed on resistance exercise
      and nutrition as potential therapeutic countermeasures, we consider recent
      advancements in the study of resistance exercise and nutrition in the stimulation
      of muscle protein synthesis and the associated implications when devising
      effective treatment strategies.

PMID- 22951157
TI  - Comment re. Obesity: The preventive role of the pomegranate (Punica granatum).

PMID- 22951158
TI  - Heme iron-based dietary intervention for improvement of iron status in young
      women.
AB  - OBJECTIVE: Conventional iron deficiency treatment with pharmacologic iron doses
      often causes side effects. Heme iron has high bioavailability and a low capacity
      to cause gastrointestinal side effects. This study investigated the possibility
      of using heme iron in the form of blood-based crisp bread as a diet-based
      treatment program to improve the iron status of women of reproductive age.
      METHODS: In a 12-wk intervention study, 77 women (mean age 24 y) were assigned to
      one of four groups: blood-based crisp bread (35 mg of iron [Fe], 27 mg of which
      was heme Fe), iron supplementation consisting of 35 mg of non-heme iron/day
      (Fe35), iron supplementation consisting of 60 mg of non-heme iron/day (Fe60), and
      controls (iron-free tablets). RESULTS: Body iron increased significantly in the
      crisp bread group by a median of 2.7 mg/kg (interquartile range 3.1, n = 18), in
      the Fe35 group by 2.7 mg/kg (interquartile range 2.8, n = 11), and in the Fe60
      group by 4.1 mg/kg (interquartile range 3.6, n = 13), whereas no change was
      observed in the control group. No statistically significant difference in iron
      status increase was observed between the crisp bread group compared with the two
      iron-supplemented groups. CONCLUSION: Dietary-based treatment containing heme
      iron has few side effects and can be used efficiently to improve the iron status
      of women of reproductive age.

PMID- 22951159
TI  - Iatrogenic prion diseases in humans: an update.
AB  - Although Creutzfeldt-Jakob disease (CJD) was first identified in 1920, prevention
      of transmission raised particular concern all over the world when a new variant
      of the disease was first described in 1996. There is good evidence of iatrogenic
      transmission of this new variant among human beings through blood, blood
      components, tissues and growth hormone. Furthermore, four cases of iatrogenic
      transmission of CJD through fertility treatment with human pituitary-derived
      gonadotrophins have been reported. It is important to distinguish the categories
      of infectivity and categories of risk, which require consideration not only of
      the level of infectivity of a given tissue or fluid, but also the amount of
      tissue/fluid to which a person is exposed, the duration of exposure and the route
      by which infection is transmitted. The potential presence and infectivity of
      prion proteins in human urinary gonadotrophin preparations is a matter of debate.
      Differences in the sensitivity of bioassay methods are of paramount importance
      when considering the infectivity of a tissue. Some new methods might detect small
      amounts of agent in some tissues currently thought to be free of infectivity. No
      cases of human prion disease due to the use of urinary gonadotrophins have been
      recognized to date. However, the detection of prions in the urine of experimental
      animals and in some urine-based preparations, and the young age of fertility drug
      recipients, require the application of the precautionary principle to urinary
      preparations.

PMID- 22951160
TI  - The value of perioperative mitomycin C instillation in improving subsequent
      bacillus calmette-guerin instillation efficacy in intermediate and high-risk
      patients with non-muscle invasive bladder cancer: a prospective randomized study.
AB  - PURPOSE: We evaluated the efficacy of perioperative mitomycin C (MMC)
      instillation to improve subsequent bacillus Calmette-Guerin (BCG) instillation
      efficacy in intermediate and high risk patients with non-muscle invasive bladder
      cancer (NMIBC). MATERIALS AND METHODS: From November 2004 to May 2006, 51
      patients with intermediate or high risk NMIBC were enrolled in this prospective
      randomized trial. In group A, patients were treated with perioperative MMC (40 mg
      MMC in 40 mL saline was administered within 6 hours of surgery) followed by
      delayed (at least 15 days from surgery) BCG instillations (once a week for 6
      weeks, 5 x 108 colony-forming units in 50 mL saline). Patients in group B were
      treated with delayed BCG instillations alone. The primary end points were
      recurrence-free interval and recurrence rate. RESULTS: There were 25 and 26
      patients in groups A and B, respectively. Median follow-up was 41.3 months (range
      8 to 64) in group A and 40.9 months (range 6 to 68) in group B. Recurrence rate
      was 36 % (9 of 25) and 19.3 % (5 of 26) in group A and B, respectively (p =
      0.052). Median time to the first recurrence was 8 months in group A and 7 months
      in group B (p = 0.12). CONCLUSIONS: The present study showed no statistically
      significant difference in terms of recurrence rate and median time to first
      recurrence between intermediate or high-risk patients with NMIBC who were treated
      with early single dose instillation of MMC plus delayed BCG and those who were
      treated with only BCG.

PMID- 22951161
TI  - PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut
      off: 20 or 35?
AB  - PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients
      undergoing repeated saturation prostate biopsy (SPBx). MATERIAL AND METHODS: From
      January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative
      extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent
      suspicion of PCa. The indications for repeated biopsy were: persistently high or
      increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL
      with free/total PSA <= 25% and <= 20 %, respectively; moreover, before performing
      SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and
      median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32
      patients (27.1 %): PCA3 score was 59 (median; range: 7-201) in the presence of
      PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the
      presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40
      (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV
      and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50 %,
      90.6 vs 71.9 %, 27.9 vs 41.8 %, 31.9 vs 31.5 % and 88.9 vs 80 %, respectively.
      ROC analysis demonstrated an AUC for PCA3 >= 20 vs >= 35 of 0.678 and 0.634,
      respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an
      exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided
      22.9 vs 38.1 % of biopsies while missing 9.4 % and 28 % diagnosis of PCa.

PMID- 22951162
TI  - Influence of strict sperm morphology on the results of classic in vitro
      fertilization.
AB  - OBJECTIVE: To determine the influence of the concentration of oval spermatozoa
      according to the strict morphology criterion in men with normal sperm
      concentration following the World Health Organization criteria on the results of
      classic IVF. MATERIALS AND METHODS: Based on review of patient charts, this study
      included infertile couples presenting with female causes for infertility or
      unexplained infertility, in whom men presented with normal spermogram values for
      sperm concentration, sperm motility, volume of ejaculate and total sperm count
      after semen processing greater than 20 million. Based on the value obtained in
      strict sperm morphology, patients were divided into three groups: in Group A,
      patients with values between 0 % and 4 %; in group B, between 5 % and 14 %, and
      in group C, patients with sperm morphology greater than 14 %. The outcomes
      analyzed were oocyte fertilization rate, biochemical pregnancy rate, clinical
      pregnancy rate and rate of liveborns. RESULTS: A total of 244 cases met the
      inclusion criteria, 27 of them in group A, 165 in group B, and 52 in group C. The
      mean fertilization rate and the rate of liveborns were, respectively: 71.9 % and
      33.3 % in group A; 80.9 % and 24.2 % in group B, and 78.8 % and 28.8 % in group
      C. There was no statistical difference among the groups in any of the outcomes
      analyzed. CONCLUSION: The values of strict sperm morphology, as proposed by
      Kruger and adopted by the World Health Organization, had no infl uence on the
      results of classic in vitro fertilization in the studied sample.

PMID- 22951163
TI  - Structural alterations of foreskin caused by chronic smoking may explain high
      levels of urethral reconstruction failure using foreskin flaps.
AB  - OBJECTIVES: The aim of the present study was to perform a stereological and
      biochemical analysis of the foreskin of smoker subjects. MATERIALS AND METHODS:
      Foreskin samples were obtained from 20 young adults (mean = 27.2 years old)
      submitted to circumcision. Of the patients analyzed, one group (n = 10) had
      previous history of chronic smoking (a half pack to 3 packs per day for 3 to 13
      years (mean = 5.8 +/- 3.2). The control group included 10 nonsmoking patients.
      Masson 's trichrome stain was used to quantify the foreskin vascular density.
      Weigert's resorcin-fucsin stain was used to assess the elastic system fibers and
      Picrosirius red stain was applied to study the collagen. Stereological analysis
      was performed using the Image J software to determine the volumetric densities.
      For biochemical analysis, the total collagen was determined as ug of
      hydroxyproline per mg of dry tissue. Means were compared using the unpaired t
      test (p < 0.05). RESULTS: Elastic system fibers of smokers was 42.5 % higher than
      in the control group (p = 0.002). In contrast, smooth muscle fibers (p = 0.42)
      and vascular density (p = 0.16) did not show any significant variation.
      Qualitative analysis using Picrosirius red stain with polarized light evidenced
      the presence of type I and III collagen in the foreskin tissue, without
      significant difference between the groups. Total collagen concentration also did
      not differ significantly between smokers and non-smokers (73.1 ug/mg +/- 8.0 vs.
      69.2 ug/mg +/- 5.9, respectively, p = 0.23). CONCLUSIONS: The foreskin tissue of
      smoking patients had a significant increase of elastic system fibers. Elastic
      fibers play an important role in this tissue's turnover and this high
      concentration in smokers possibly causes high extensibility of the foreskin. The
      structural alterations in smokers' foreskins could possibly explain the poor
      results in smoking patients submitted to foreskin fasciocutaneous flaps in
      urethral reconstruction surgery.

PMID- 22951164
TI  - Expression of VEGF and collagen using a latex biomembrane as bladder replacement
      in rabbits.
AB  - OBJECTIVE: To investigate the VEGF expression and collagen deposition using a
      latex biomembrane as bladder replacement in rabbits. MATERIALS AND METHODS: After
      partial cystectomy, a patch of a non-vulcanized latex biomembrane (2 x 2 cm) was
      sewn to the bladder of rabbits with 5/0 monofilament polydioxanone sulfate
      sutures in a watertight manner. Groups of 5 animals were killed at 15, 45 and 90
      days after surgery and the bladder was removed. Sections of 5um were cut and
      stained with picrosirius-red in order to estimate the amount of extracellular
      matrix in the graft. To confirm the presence of VEGF in tissues, protein
      expression was determined by immunohistochemistry. RESULTS: No death, urinary
      leakage or graft extrusion occurred in any group. All bladders showed a spherical
      shape. A progressive reduction in the amount of collagen occurred in the graft
      area and was negatively and linearly correlated with time (p < 0.001). VEGF
      expression was higher in grafted areas when compared to controls at 15 and 45
      days after surgery and decreased with time (p < 0.001). CONCLUSION: The latex
      biomembrane as a matrix for partial bladder replacement in rabbits promotes
      temporary collagen deposition and stimulates the angiogenic process.

PMID- 22951165
TI  - Characterization of the deposition of collagen fibers and lithogenic potential in
      bladder of rats submitted to a sugar cane biopolymer graft.
AB  - OBJECTIVES: Suture materials are widely used in urology. The interaction of these
      materials with the extracellular matrix in the inflammatory process can be
      estimated by stereology of collagen fibers and the present study was designed to
      determine the behavior of the bladder tissue of rats to grafts of the biopolymer
      of sugar cane (BPCA), and the inflammation and intravesical stone formation
      compared to the polyglactin 910. MATERIALS AND METHODS: 42 Wistar rats were
      divided in four groups: Group I (n = 10) rats submitted to bladder implantation
      of ~4-0 BPCA suture graft and euthanized at 4 weeks; Group II (n = 10) rats
      submitted to bladder implantation of 4-0 polyglactin 910 suture graft and
      euthanized at 4 weeks; Group III (n = 12) rats submitted to bladder implantation
      of ~4-0 BPCA suture graft and euthanized at 8 weeks; Group IV (n = 10) rats
      submitted to bladder implantation of 4-0 polyglactin 910 suture graft and
      euthanized at 8 weeks. Bladders collected at necropsy were analyzed for their
      weight and the presence of grafts and calculi. Sections were prepared for
      stereological analysis of collagen fibers. RESULTS: The bladder weight was higher
      in group I, particularly in the presence of bladder stones. The presence of the
      graft was observed in 100 % (group I), 80 % (group II), 91.6 % (group III) and 30
      % (group IV); polyglactin 910 showed an absorption of 70 % in this period. The
      stereological analysis showed a higher volume density of collagen fibers in group
      I versus other groups (p < 0.001). CONCLUSION: The BPCA was a material with good
      integration into the bladder of rats; its absorption was slower than that of the
      polyglactin 910. The presence of urinary stones was lower in bladders with
      implantation of BPCA, particularly after 8 weeks. There was a greater initial
      inflammatory response to BPCA graft that was directly related to the increase in
      bladder weight and the presence of urinary stones, but that equalized the results
      of polyglactin 910 after 8 weeks.

PMID- 22951166
TI  - Influence of oxidative stress on inducing micturition dysfunction following
      chronic infravesical obstruction and the protective role of an antioxidant diet -
      association of in vivo and in vitro studies in rats.
AB  - OBJECTIVE: This study was developed to determine whether the generation of free
      radicals, induced by ischemia followed by reperfusion in a model of chronic
      intravesical obstruction in rats, would lead to damage in the detrusor. It also
      investigates the possible protective action of the flavonoid galangin on the
      tissue lesion induced by lipid peroxidation. MATERIALS AND METHODS: Twenty-one
      male rats were divided into three groups of seven animals each. Group A was
      subjected to a sham procedure; group B to partial obstruction of the bladder
      neck; and group C to partial obstruction of the bladder neck, but also received a
      diet rich in the flavonoid galangin. All the animals were subjected to urodynamic
      evaluation and then sacrificed. The bladders were sent for enzymatic tests.
      RESULTS: The urodynamic showed that group B developed significantly greater
      numbers of involuntary contractions of the detrusor, greater post-micturition
      residue and lower compliance. The group A presented TEAC levels greater than to
      the group B. Comparative analysis of group A, B and C demonstrated significantly
      greater malondialdehyde levels in group B in relation to groups A and C. The
      group B presented smaller contraction amplitudes than did groups A and C, in
      electrically stimulated contractions. CONCLUSIONS: That oxidative stress is
      implicated in the damage to the detrusor musculature following a period of
      chronic intravesical obstruction. We show, for the first time, that
      administration of an antioxidant prior to and following the start of chronic
      obstruction makes it possible to avoid the cellular lesions that cause detrusor
      dysfunction.

PMID- 22951167
TI  - Microscopic hematuria and pelvic congestion syndrome in a patient with cirrhosis.

PMID- 22951168
TI  - CT diagnosis of foreign body in urinary bladder after surgical management of
      stress urinary incontinence.

PMID- 22951169
TI  - Ventral phalloplasty.
AB  - PURPOSE: To present the surgical technique of ventral phalloplasty as an adjunct
      procedure to the classic prosthetic surgery. MATERIALS AND METHODS: In this video
      we demonstrate how to perform a ventral phalloplasty in a patient that has
      undergone a penile prosthesis implantation. Our technique consists of:
      delineation of the penile scrotal web, excision of this redundant skin, and re
      approximation of the wound to mimic the natural median raphe. RESULTS: The
      ventral phalloplasty improves the perception of phallic length, as well as
      patients' satisfaction after prosthetic surgery. CONCLUSION: Penile length
      perception is the main concern of patients that have undergone penile prosthesis
      implantation. In this video we demonstrate that the ventral phalloplasty can
      improve perception of phallic length, and can be an important adjunct to the
      classic prosthetic surgery.

PMID- 22951170
TI  - Re: Video-assisted left inguinal lymphadenectomy for penile cancer.

PMID- 22951172
TI  - The prevalence of prostate cancer in Brazil is higher in Black men than in White
      men: systematic review and meta-analysis.
AB  - BACKGROUND: Black men have a higher incidence of prostate cancer compared with
      White men in several countries. In Brazil, most studies reported a similar
      prevalence of prostate cancer between Blacks and Whites as a result of the high
      race mixture of the population. OBJECTIVE: To perform a systematic review with
      meta-analysis of the prevalence of prostate cancer in Black versus White, Brown
      versus White, and Black versus Brown Brazilian men. DESIGN, SETTING, AND
      PARTICIPANTS: This systematic review included cohort, cross sectional and case
      control studies comparing the prevalence of prostate cancer between races in
      Brazil. It was performed using an electronic search of references in
      bibliographic databases, and dissertations and theses databases from several
      Brazilian hospitals, universities, and schools of medicine. Meta-analysis was
      conducted using the RevMan software from the Cochrane Collaboration. To control
      for potential confounding variables, sensitivity analyses excluding case-control
      and cross sectional studies were performed. MEASUREMENTS: The outcomes of
      interest included the number of participants, prevalence of prostate cancer, and
      odds ratio of cancer between Black and White men, Brown and White men, and Black
      and Brown men. RESULTS AND LIMITATIONS: Twelve studies approaching the prevalence
      of prostate cancer in Black or Brown vs. White men in Brazil were identified,
      totalizing 41388 participants. The prevalence of prostate cancer was 9.6% in
      Black vs. 5.6% in White men (OR 1.58), 10.1% in Black vs. 6.7% in Brown men (OR
      1.43), and 6.7% in Brown vs. 6.6% in White men (OR 1.14). Limitations of this
      review reflect the complexity and ambiguity in the definition of who is Black and
      who is not in such an heterogeneous population like the Brazilian people.
      CONCLUSIONS: This systematic review with meta-analysis demonstrates a higher
      prevalence of prostate cancer in Black men compared to White or Brown Brazilian
      men. The prevalence of prostate cancer is similar in Brown versus White men.

PMID- 22951173
TI  - Antegrade pressure measurement of urinary tract in children with persistent
      hydronephrosis.
AB  - INTRODUCTION: Dilation of urinary tract occurs without the presence of
      obstruction. Diagnostic methods that depend on renal function may elicit mistaken
      diagnosis. Whitaker (1973) proposed the evaluation of urinary tract pressure
      submitted to constant flow. Other investigators proposed perfusion of renal
      pelvis under controlled pressure, making the method more physiological and
      reproducible. The objective of the present study was to evaluate the results of
      the anterograde pressure measurement (APM) of the urinary tract of children with
      persistent hydronephrosis after surgery suspected to present persistent
      obstruction. MATERIALS AND METHODS: Along 12 years, 26 renal units with
      persistent hydronephrosis after surgery (12 PUJ and 14 VUJ) were submitted to
      evaluation of the renal tract pressure in order to decide the form of treatment.
      Previous radionuclide scans with DTPA, intravenous pyelographies and ultrasounds
      were considered undetermined in relation to obstruction in 10 occasions and
      obstructive in 16. APM was performed under radioscopy through renal pelvis
      puncture or previous stoma. Saline with methylene blue + iodine contrast was
      infused under constant pressure of 40 cm H2O to fill the urinary system. The
      ureteral opening pressure was measured following the opening of the system and
      stabilization of the water column. RESULTS: Among the 10 cases with undetermined
      previous diagnosis, APM was considered non-obstructive in two and those were
      treated clinically and eight were considered obstructive and were submitted to
      surgery. Among the 16 cases previously classified as obstructive, nine confirmed
      obstruction and were submitted to surgery. Seven cases were considered non
      obstructive, and were treated clinically, with stable DMSA and hydronephrosis.
      CONCLUSIONS: APM avoided unnecessary surgery in one third of the cases and was
      important to treatment decision in 100 %. We believe that this simple test is an
      excellent diagnostic tool when selectively applied mainly in the presence of
      functional deficit.

PMID- 22951174
TI  - Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent
      prognostic significance.
AB  - PURPOSE: To analyze the immunohistochemical expression of the standard isoform of
      CD44 (CD44s) adhesion molecule in clear cell renal cell carcinoma (CCRCC) and its
      impact on clinical outcomes. MATERIALS AND METHODS: Ninety-nine consecutive
      patients treated surgically for RCC between 1992 and 2009 were selected. A single
      pathologist reviewed all cases to effect a uniform reclassification and determine
      the most representative tumor areas for construction of a tissue microarray. The
      same pathologist, who was blinded to the outcome of the cases, semi
      quantitatively scored the staining intensity of CD44s in all specimens. The
      counting was done using the H-Score algorithm. RESULTS: Of the 99 immunostained
      RCC specimens, 57(57.7 %) showed low expression, and 42(42.4 %) showed high
      expression levels of CD44s. The expression of CD44s was directly associated with
      tumor size (p = 0.03), clinical stage (p = 0.02) and Fuhrman grade (p = 0.02).
      Disease specifi c survival (DSS) rates for patients whose specimens expressed low
      and high levels of CD44s was 88.1 % and 67.5 %, respectively (p = 0.009).
      Progression free survival (PFS) rates in patients with low and high expression of
      CD44s were 78.8 % and 61.7 %, respectively (p = 0.05). Classical features such as
      the presence of metastasis and clinical stage remained isolated predictors of
      survival. CONCLUSIONS: Immunohistochemical expression of CD44s was associated
      with important clinical variables such as stage and Fuhrman grade. However, it
      was not an independent predictor of survival. Therefore, we believe it has a
      limited role as a prognostic marker in patients with CCRCC.

PMID- 22951175
TI  - Twenty-five milligrams of clomiphene citrate presents positive effect on
      treatment of male testosterone deficiency - a prospective study.
AB  - INTRODUCTION: Male testosterone deficiency is associated with bad sexual function
      and quality of life (QoL). The aim of this study was to determine whether a daily
      dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous
      testosterone production pathway and to address the applicability of this
      medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND
      METHODS: This was a prospective study. Men with low sexual desire and
      testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood
      samples were obtained to determine baseline measurements of serum T, estradiol,
      LH, lipid profile and fasting plasma glucose. Each patient was treated with a
      daily dose of 25 mg CC for at least 3 months. Patients were asked if they
      experienced any side effects related to the use of CC and if they experienced any
      improvement in their sexual profile. Paired samples T-test was utilized to
      analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with
      hypogonadism and low libido. Mean age was 62 years (+/- 11.1 years). Serum T
      levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after
      CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197
      to 186 mg/dL (p = 0.003). There were no statistically significant differences
      when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting
      plasma glucose and prolactin. All men reported improvements in the post-treatment
      QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was
      effective in stimulating the endogenous production of testosterone. A lower level
      of total cholesterol was verified after three months of treatment. This
      medication should be considered as a therapeutic option for some patients with
      symptomatic male testosterone deficiency.

PMID- 22951176
TI  - Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion
      molecules and prognosis for upper urinary tract urothelial carcinomas.
AB  - INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal
      epithelial phenotype, and abnormalities in CAM expression have been related to
      cancer progression, including bladder urothelial carcinomas. There is only one
      study that correlates E-cadherin and Alpha-, Beta- and y-catenin expression with
      prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern
      of immune expression of these CAMs in urothelial carcinomas from the renal pelvis
      and ureter in patients who have been treated surgically. Our goal is to correlate
      these expression levels and characteristics with well-known prognostic parameters
      for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20
      patients with urothelial carcinomas of the renal pelvis and ureter who were
      treated with nephroureterectomy or ureterectomy between June 1997 and January
      2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray
      and correlated with histopathological characteristics and patient outcomes after
      a mean follow-up of 55 months. RESULTS: We observed a relationship between E
      cadherin expression and disease recurrence. Disease recurrence occurred in 87.5%
      of patients with strong E-cadherin expression. Only 50.0% of patients with
      moderate expression and 0% of patients with weak or no expression of E-cadherin
      had disease recurrence (p = 0.014). There was also a difference in disease-free
      survival. Patients with strong E-cadherin expression had a mean disease-free
      survival rate of 49.1 months, compared to 83.9 months for patients with moderate
      expression (p = 0.011). Additionally, an absence of Alpha-catenin expression was
      associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We
      demonstrated for the first time that immune expression of E-cadherin is related
      to tumor recurrence and disease-free survival rates, and the absence of Alpha
      catenin expression is related to tumor size in upper tract urothelial carcinomas.

PMID- 22951177
TI  - Clampless laparoscopic partial nephrectomy: a step towards a harmless nephron
      sparing surgery?
AB  - PURPOSE: To evaluate the results of our technique of clampless laparoscopic
      partial nephrectomy (LPN) and its impact as an emerging treatment for small renal
      masses (SMRs). MATERIALS AND METHODS: We reviewed our prospectively maintained
      database: data of 117 patients who consecutively underwent LPN at our Institution
      from January 2009 to December 2011 were studied. Patients were divided into 2
      Groups based on operative technique: Group A: clampless-LPN (cl-LPN); Group B:
      conventional LPN (clamping of renal artery). Demographic and peri-operative data,
      complications, pre- and post-operative serum creatinine and estimated glomerular
      filtration rate (eGFR) were registered and compared by Student's t- and Chi
      square-tests (p-values < 0.05 considered statistically significant). RESULTS: 41
      patients were in Group A and 76 in Group B. Groups were comparable in terms of
      preoperative data except for tumour's size (2.35 +/- 1.10 vs. 3.19 +/- 1.57,
      Group A vs. B, respectively, p = 0.0029). Concerning perioperative data, warm
      ischemia time (WIT) was 0 min. in all Group A cases; mean WIT in Group B was
      20.90 +/- 9.27 min. One case (2.4%) in Group A (central tumour) was converted to
      conventional LPN. Mean eGFR postoperative decrease was higher in Group B (0.17 +/
      9.30 vs. 4.38 +/- 11.37 mL/min., A vs B, respectively, p = 0.0445). CONCLUSIONS:
      Notwithstanding the limits of the study, our results suggest that cl-LPN is a
      safe and effective technique, which allows surgeon to surgically treat SRMs even
      in case of complex location, without injuring kidney by ischemia.

PMID- 22951178
TI  - Early outcomes of laparoscopic donor nephrectomy with multiple renal arteries.
AB  - PURPOSE: We evaluated our experience with laparoscopic donor nephrectomy in
      patients with multiple renal arteries, comparing operative outcomes and early
      graft function with patients with a single renal artery. MATERIALS AND METHODS:
      From January 2003 to February 2009, 130 patients underwent laparoscopic donor
      nephrectomy at our institution, 108 (83 %) with a single renal artery and 22 (17
      %) with multiple arteries. Donor and recipient outcomes for single artery and
      multiple arteries allografts were compared. RESULTS: The LDN operative time was
      similar between the single artery and multiple arteries groups (162 vs 163 min,
      respectively, p = 0.87). Allografts with multiple arteries had significantly
      longer warm ischemia time (3.9 vs 4.9 min, p = 0.05) and cold ischemia time (72
      vs 94 min, p < 0.001) than those with single artery. The conversion rate was
      similar between single and multiple arteries groups (6 % vs 4.5 %, respectively,
      p = 0.7). Multiple arteries grafts had a non statistically significant higher
      rate of poor graft function when compared to single artery grafts (23 % vs 12 %,
      respectively, p = 0.18). Five patients in the single artery group (4.6 %) and one
      patient in the multiple arteries group (4.5 %) needed dialysis during the first
      postoperative week. Overall, recipient complication rates were similar between
      single and multiple arteries groups (12.9 % vs 18.1 %, respectively, p = 0.51).
      CONCLUSION: Laparoscopic donor nephrectomy with multiple arteries was associated
      with a non statistically significant higher rate of poor early graft function.
      The procedure appears to be safe in patients with multiple arteries, with similar
      complications rates. Multiple arteries should not be a contraindication for
      laparoscopic donor nephrectomy.

PMID- 22951179
TI  - Efficacy and safety of percutaneous nephrolithotomy (PCNL): a prospective and
      randomized study comparing regional epidural anesthesia with general anesthesia.
AB  - OBJECTIVE: To compare the efficacy and safety of regional epidural anesthesia and
      general anesthesia in patients who underwent PCNL. MATERIALS AND METHODS: Fifty
      patients submitted to percutaneous nephrolithotomy (PCNL) were randomized into
      two groups: Group I (N = 26) received general anesthesia and Group II (N = 24)
      received regional epidural anesthesia. Demographic and operative data including
      age, BMI, stone position, stone size, postoperative pain, amount of postoperative
      analgesic usage, length of hospital stay, patient satisfaction, preoperative and
      postoperative hemoglobin and hematocrit, adverse effects and surgical
      complications were compared between both groups. RESULTS: Average pain score at 1
      hour. was 6.88 in group I and 3.12 in group II (p < 0.001), at 4 hours. 5.07 in
      group I and 3.42 in group II (p = 0.025). Less morphine was required in the
      regional epidural anesthesia group compared to the general anesthesia group.
      Higher satisfaction was found in the regional epidural group. 6 (23.07 %)
      patients in Group I and 1 patient (4.19 %) in Group II had postoperative nausea
      and vomiting, respectively (p = 0.05). Pain score at 12 hours, 24 hours, 48
      hours, 72 hours, preoperative and postoperative hemoglobin and hematocrit, length
      of hospital stay, and adverse effects were no different between the two groups.
      CONCLUSION: Regional epidural anesthesia is an alternative technique for PCNL
      which achieves more patient satisfaction, less early postoperative pain and less
      adverse effects from medication with the same efficacy and safety compared to
      general anesthesia.

PMID- 22951181
TI  - Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits
      induced by scopolamine or MK-801.
AB  - The objective of this study was to assess the effects of phosphodiesterase type 2
      (PDE2) and type 10 (PDE10) inhibition on memory function in the object
      recognition task using the scopolamine- and MK-801-induced memory deficit model.
      The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on
      object recognition performance were investigated in the scopolamine (0.1mg/kg,
      i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of
      0.3-3mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1mg/kg (p.o.)
      in the scopolamine model and 0.3-3mg/kg in the MK-801 model. All compounds were
      injected 30 min before the learning trial. Both BAY 60-7550 (1mg/kg) and PQ-10
      (0.3mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced
      memory deficit was reversed after treatment with each PDE inhibitor at a dose of
      1mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the
      brain were very low after oral treatment. We concluded that since BAY 60-7550 and
      PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports
      the notion that dual substrate PDE inhibitors might be suitable candidates for
      cognition enhancement.

PMID- 22951180
TI  - High-throughput screening of stem cell therapy for globoid cell leukodystrophy
      using automated neurophenotyping of twitcher mice.
AB  - Globoid cell leukodystrophy (Krabbe's disease) is an autosomal recessive
      neurodegenerative disorder that results from the deficiency of
      galactosylceramidase, a lysosomal enzyme involved in active myelination. Due to
      the progressive, lethal nature of this disease and the limited treatment options
      available, multiple laboratories are currently exploring novel therapies using
      the mouse model of globoid cell leukodystrophy. In order to establish a protocol
      for motor function assessment of the twitcher mouse, this study tested the
      capability of an automated system to detect phenotypic differences across mouse
      genotypes and/or treatment groups. The sensitivity of this system as a screening
      tool for the assessment of therapeutic interventions was determined by the
      administration of murine bone marrow-derived stem cells into twitcher mice via
      intraperitoneal injection. Animal behavior was analyzed using the Noldus
      EthoVision XT7 software. Novel biomarkers, including abnormal locomotion (e.g.,
      velocity, moving duration, distance traveled, turn angle) and observed behaviors
      (e.g., rearing activity, number of defecation boli), were established for the
      twitcher mouse. These parameters were monitored across all mouse groups, and the
      automated system detected improved locomotion in the treated twitcher mice based
      on the correction of angular velocity, turn angle, moving duration, and
      exploratory behavior, such as thigmotaxis. Further supporting these findings, the
      treated mice showed improved lifespan, gait, wire hang ability, twitching
      severity and frequency, and sciatic nerve histopathology. Taken together, these
      data demonstrate the utility of computer-based neurophenotyping for motor
      function assessment of twitcher mice and support its utility for detecting the
      efficacy of stem cell-based therapy for neurodegenerative disorders.

PMID- 22951182
TI  - Suboptimal maternal nutrition during early fetal kidney development specifically
      promotes renal lipid accumulation following juvenile obesity in the offspring.
AB  - Reduced maternal food intake between early-to-mid gestation results in tissue
      specific adaptations in the offspring following juvenile-onset obesity that are
      indicative of insulin resistance. The aim of the present study was to establish
      the extent to which renal ectopic lipid accumulation, as opposed to other markers
      of renal stress, such as iron deposition and apoptosis, is enhanced in obese
      offspring born to mothers nutrient restricted (NR) throughout early fetal kidney
      development. Pregnant sheep were fed either 100% (control) or NR (i.e. fed 50% of
      their total metabolisable energy requirement from 30-80 days gestation and 100%
      at all other times). At weaning, offspring were made obese and, at approximately
      1 year, kidneys were sampled. Triglyceride content, HIF-1alpha gene expression
      and the protein abundance of the outer-membrane transporter voltage-dependent
      anion-selective channel protein (VDAC)-I on the kidney cortex were increased in
      obese offspring born to NR mothers compared with those born to controls, which
      exhibited increased iron accumulation within the tubular epithelial cells and
      increased gene expression of the death receptor Fas. In conclusion, suboptimal
      maternal nutrition coincident with early fetal kidney development results in
      enhanced renal lipid deposition following juvenile obesity and could accelerate
      the onset of the adverse metabolic, rather than cardiovascular, symptoms
      accompanying the metabolic syndrome.

PMID- 22951183
TI  - Effectiveness of multicultural health workers in chronic disease prevention and
      self-management in culturally and linguistically diverse populations: a
      systematic literature review.
AB  - With a large and increasing culturally and linguistically diverse (CALD)
      population, the Australian health care system faces challenges in the provision
      of accessible culturally competent health care. Communities at higher risk of
      chronic disease include CALD communities. Overseas, multicultural health workers
      (MHWs) have been increasingly integrated in the delivery of culturally relevant
      primary health care to CALD communities. The objective of this systematic review
      was to examine the effectiveness of MHW interventions in chronic disease
      prevention and self-management in CALD populations with the aim to inform policy
      development of effective health care in CALD communities in Australia. A
      systematic review protocol was developed and computerised searches were conducted
      of multiple electronic databases from 1 January 1995 until 1 November 2010.
      Thirty-nine studies were identified including 31 randomised controlled trials.
      Many of the studies focussed on poor and underserved ethnic minorities. Several
      studies reported significant improvements in participants' chronic disease
      prevention and self-management outcomes and meta-analyses identified a positive
      trend associated with MHW intervention. Australian Government policies express
      the need for targeted inventions for CALD communities. The broader systemic
      application of MHWs in Australian primary health care may provide one of the most
      useful targeted interventions for CALD communities.

PMID- 22951184
TI  - Developmental profile of localized spontaneous Ca(2+) release events in the
      dendrites of rat hippocampal pyramidal neurons.
AB  - Recent experiments demonstrate that localized spontaneous Ca(2+) release events
      can be detected in the dendrites of pyramidal cells in the hippocampus and other
      neurons (J. Neurosci. 29 (2009) 7833-7845). These events have some properties
      that resemble ryanodine receptor mediated "sparks" in myocytes, and some that
      resemble IP(3) receptor mediated "puffs" in oocytes. They can be detected in the
      dendrites of rats of all tested ages between P3 and P80 (with sparser sampling in
      older rats), suggesting that they serve a general signaling function and are not
      just important in development. However, in younger rats the amplitudes of the
      events are larger than the amplitudes in older animals and almost as large as the
      amplitudes of Ca(2+) signals from backpropagating action potentials (bAPs). The
      rise time of the event signal is fast at all ages and is comparable to the rise
      time of the bAP fluorescence signal at the same dendritic location. The decay
      time is slower in younger animals, primarily because of weaker Ca(2+) extrusion
      mechanisms at that age. Diffusion away from a brief localized source is the major
      determinant of decay at all ages. A simple computational model closely simulates
      these events with extrusion rate the only age dependent variable.

PMID- 22951185
TI  - Gender differences in nighttime sleep and daytime napping as predictors of
      mortality in older adults: the Rancho Bernardo study.
AB  - OBJECTIVE: Many studies suggest optimal sleep duration for survival is 7
      8h/night. We report the gender-specific independent association of all-cause
      mortality with nighttime sleep and daytime nap duration in older adults who were
      followed for up to 19years. METHODS: Between 1984 and 1987, 2001 community
      dwelling, mostly retired, adults (1112 women), age 60-96years, answered questions
      about health, mood, medications, life-style, daytime napping, and nighttime sleep
      duration. Vital status was confirmed for 96% through July 2001. RESULTS: At
      baseline, men reported significantly longer nighttime sleep and daytime napping
      than women. In both men and women, nighttime sleep <6h was associated with
      depressed mood and sleep-related medication, and ?9h was associated with more
      alcohol consumption. Napping ?30min was associated with prevalent depressed mood,
      coronary heart disease, and cancer. Of the group, 61% died over the next 19years,
      at an average age of 85.6years. Mortality risk was lowest among those sleeping 7
      7.9h/night in both men and women. Multiple-adjusted analyses showed that
      increased mortality was associated with nighttime sleep ?9h in women (HR 1.51:
      95% CI=1.05-2.18), and with daytime napping ?30min in men (HR 1.28: 95% CI, 1.00
      1.64). CONCLUSIONS: Mechanisms for these differences are unknown.

PMID- 22951186
TI  - Prevalence and factors associated with snoring in 3-year olds: early links with
      behavioral adjustment.
AB  - OBJECTIVE: Identify the prevalence of sleep disordered breathing (SDB) symptoms
      in a community sample of New Zealand 3-year olds. To examine sleep, demographic,
      health, environmental, familial, perinatal, and behavioral adjustment factors
      associated with habitual snoring. METHODS: A cross sectional study, in which
      parents of 823 children aged 3 years 0 months to 3 years 12 months (M:F=1:0.9)
      were recruited from the community. Participants completed questionnaires designed
      to assess information relevant to their children's sleep, with a particular focus
      on snoring. RESULTS: Parents reported snoring at least once a week in 36.9% of
      children, and habitual snoring (more than four nights per week) in 11.3% of
      children. Univariate analysis showed habitual snoring was more common amongst
      Maori (indigenous New Zealanders) (P=0.04) and males (P=0.05), and that habitual
      snorers came from more socio-economically deprived neighborhoods (P<0.01).
      Several other SDB-related symptoms were significantly associated with habitual
      snoring: mouth breathing, sweating profusely, waking during the night, sleeping
      with neck extended, constant runny nose, and suffering from tonsillitis. Mouth
      breathing was the most strongly associated. Multivariate analyzes revealed a
      strong positive relationship between snoring and some health and familial
      factors, as well as parent reported child irritability (OR=2.83; 95% CI 1.4-5.6)
      and hyperactivity (OR=1.6; 95% CI 1.0-2.7). CONCLUSIONS: The prevalence of
      habitual snoring amongst New Zealand pre-schoolers is similar to that reported
      elsewhere. Factors associated with habitual snoring include male gender, Maori
      ethnicity, and poorer deprivation neighborhood, as well as a variety of other
      environmental and health factors. The data provide evidence that habitual snoring
      associated with irritable and hyperactive behavior is evident in children as
      young as three.

PMID- 22951187
TI  - Oxidative stress parameters in serum and low density lipoproteins of Hashimoto's
      thyroiditis patients with subclinical and overt hypothyroidism.
AB  - BACKGROUND: Although prooxidant and antioxidant status were reported to be
      changed in clinical and experimental hypothyroidism, obtained results are
      conflicting. In addition, in subclinical hypothyroidism, scarced and
      controversial data are available about oxidative stress. Therefore, we aimed to
      investigate prooxidant-antioxidant status only in Hashimoto's thyroiditis (HT)
      patients with subclinical (sHT) and overt hypothyroidism (oHT). SUBJECTS AND
      METHODS: Thirty sHT and 18 oHT patients and 30 healthy control subjects were
      included in the study. Endogenous and prooxidant 2,2'-azobis-(2-amidinopropane)
      hydrochloride (AAPH)-induced malondialdehyde (MDA), diene conjugate (DC), protein
      carbonyl (PC) and nitrotyrosine (NT) levels as well as ferric reducing
      antioxidant power (FRAP) were determined in serum. In addition, endogenous DC and
      copper-induced MDA levels were measured in low density lipoprotein (LDL)
      fraction. RESULTS: Although there were no significant difference in serum
      endogenous MDA and DC levels, AAPH-induced MDA levels were significantly
      increased in sHT patients. All these parameters increased in oHT patients. Serum
      PC levels were detected to be increased in both sHT and oHT patients. Serum FRAP
      values did not alter in sHT patients, but they lowered in oHT patients.
      Endogenous DC and copper-induced MDA levels in LDL fraction did not change in sHT
      patients. However, these parameters were detected to be increased significantly
      in oHT patients as compared to controls and sHT patients. CONCLUSION: In
      conclusion, there were significant increases in oxidative stress parameters in
      serum and LDL-fraction in oHT patients. However, oxidative stress was detected to
      stimulate partly in serum, but not LDL fraction in sHT patients.

PMID- 22951188
TI  - Omega-3 fatty acid-derived mediator, Resolvin E1, ameliorates 2,4
      dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease for which few
      effective treatments are available. Resolvin E1 (RvE1; 5S,12R,18R-trihydroxy
      6Z,8E,10E,14Z,16E-eicosapentaenoic acid) is an endogenous lipid mediator derived
      from omega-3 fatty eicosapentaenoic acid, which is a potent inhibitor of
      inflammation. AD-like skin lesion was induced by repetitive skin contact with
      DNFB in NC/Nga mice and the effects of RvE1 were evaluated on the basis of
      histopathological findings of skin, ear swelling and cytokine production of
      CD4(+) T cells. Intraperitoneal injection of RvE1 for one week after DNFB
      challenge significantly lowered ear swelling and improved back skin lesions. In
      addition, RvE1 significantly suppressed production of interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4) by activated CD4(+) T cells and serum IgE level.
      Furthermore, RvE1 reduced DNFB-induced infiltration of eosinophils, mast cells,
      CD4(+) T cells, and CD8(+) T cells in skin lesions. Therefore, RvE1 may suppress
      the development of AD-like skin lesions in DNFB-treated NC/Nga mice by reducing
      IL-4 and IFN-gamma of activated CD4(+) T cells and serum IgE levels and
      infiltration of immune cells to skin lesion.

PMID- 22951189
TI  - Bacteriophage T7 protein kinase: Site of inhibitory autophosphorylation, and use
      of dephosphorylated enzyme for efficient modification of protein in vitro.
AB  - Bacteriophage T7 encodes a serine/threonine-specific protein kinase that
      phosphorylates multiple cellular proteins during infection of Escherichia coli.
      Recombinant T7 protein kinase (T7PK), normally purified in phosphorylated form,
      exhibits a modest level of phosphotransferase activity. A procedure is described
      that provides dephosphorylated T7PK with an enhanced ability to phosphorylate
      protein substrates, including translation initiation factor IF1 and the nuclease
      domain of ribonuclease III. Mass spectrometric analysis identified Thr12 as the
      site of IF1 phosphorylation in vitro. T7PK undergoes Mg(2+)-dependent
      autophosphorylation on Ser216 in vitro, which also is modified in vivo. The
      inability to isolate the presumptive autophosphorylation-resistant T7PK Ser216Ala
      mutant indicates a toxicity of the phosphotransferase activity and suggests a
      role for Ser216 modification in limiting T7PK activity during infection.

PMID- 22951190
TI  - Follicular fluid leptin concentrations and expression of leptin and leptin
      receptor in the equine ovary and in vitro-matured oocyte with reference to
      pubertal development and breeds.
AB  - There is no published information about follicular-fluid leptin concentrations or
      the presence of leptin and leptin receptor in the equine ovary or oocyte. Three
      groups of mares - adult draft mares, draft fillies and adult Standardbred mares -
      were included in the study. Leptin and leptin receptor were detected in all
      immature oocytes by immunofluorescence with higher intensity in oocytes from
      draft mares compared with draft fillies and Standardbred mares. After in vitro
      maturation a higher proportion of oocytes reached metaphase II in draft mares
      than in draft fillies and Standardbred mares, and in all groups both leptin and
      leptin receptor became localised in the oocyte cortex but with higher
      immunopositivity in draft mares compared with draft fillies and Standardbred
      mares. These intensities were confirmed by the expression profiles of leptin and
      leptin receptor mRNA. Moreover, leptin was detected in ovarian blood vessels in
      all three types of animal and within the corpora lutea in adult mares. Serum and
      follicular-fluid concentrations of leptin were similar in draft and Standardbred
      mares but higher in draft mares than in draft fillies. This study supports the
      hypothesis that expression of leptin and leptin receptor mRNA and the rate of
      maturation can be related either to adiposity or to puberty.

PMID- 22951191
TI  - Enhanced primary care improves GP service regularity in older patients without
      impacting on service frequency.
AB  - The objective ofthis study was to assess the impact of Enhanced Primary Care
      service utilisation on subsequent GP service regularity and frequency. The study
      involved a retrospective population-based longitudinal cohort using linked
      administrative health records of hospital and primary care services for people
      over the age of 65 years. Multinomial logistic regression modelling was used to
      evaluate changes in the relative likelihood of increased primary care service
      regularity and frequency in exposed and unexposed individuals adjusting for age,
      sex and recent chronic disease hospitalisation history. Enhanced Primary Care
      services significantly and substantially increased the relative likelihood of
      increased regularity with no corresponding higher likelihood of increased
      frequency of GP contact. Increased regularity was more likely with increasing age
      except for the oldest age group (90+ years). Some chronic disease histories (e.g.
      diabetes) showed a higher likelihood of improved regularity while others were
      less likely to produce an increased regularity (e.g. hypertension). The study
      suggests a capacity for modification of physician and patient behaviour using
      incentivised services within the current fee-for-service system in Australia.

PMID- 22951192
TI  - Abdominoperineal extralevator resection.
AB  - INTRODUCTION: Abdominoperineal resection for distal rectal cancer is associated
      with a higher recurrence rate and a poorer overall prognosis than anterior
      resection. In order to improve the outcome, a more extensive procedure -
      extralevator abdominoperineal resection - has been introduced. There are,
      however, currently no prospective or registry-based studies on the effect of this
      new procedure on local recurrence rates. MATERIAL AND METHODS: Abdominoperineal
      extralevator resection (APER) is a registry-based Swedish study investigating
      local recurrence rate three years postoperatively in the entire population of
      Swedish patients who underwent abdominoperineal resection or extralevator
      abdominoperineal resection in the 2007-2009-period. In addition to local
      recurrence rates, the study also investigates the functional and quality-of-life
      related outcome 3-4 years postoperatively in the entire study population.
      DISCUSSION: Distal rectal cancer is a surgical and oncological challenge. The
      APER study will be able to compare the two operative techniques (standard
      abdominoperineal resection or extralevator abdominoperineal resection) in terms
      of oncological and functional outcome. FUNDING: not relevant. TRIAL REGISTRATION:
      The trial is registered at ClinicalTrials.gov, identifier NCT01296984.

PMID- 22951193
TI  - Local injection of methylprednisolonacetat to prevent seroma formation after
      mastectomy.
AB  - INTRODUCTION: This study served the following three purposes: To evaluate the
      prophylactic effect against seroma of a single dose of steroid in the mastectomy
      cavity, to evaluate the thesis that there is a connection between subclinical
      bacterial colonization and seroma formation and to evaluate if a simple urine
      stix test can detect postmastectomy infection. MATERIAL AND METHODS: This was a
      double-blinded and randomized study of injection of methylprednisolonacetate
      versus saline in the mastectomy cavity at the time of drain removal. A total of
      160 females were enrolled after mastectomy. The study parameters were as follows:
      seroma volume, number of seroma punctures, frequency of clinical infections,
      degree and type of subclinical colonization, complications and evaluation of the
      microbiological results of the stix test with automatically read glucose,
      ketones, blood, pH, protein, nitrite and leucocytes. The degree of inflammation
      was monitored by measurement of 15 cytokines in each sample of seroma fluid. The
      study was initiated in August 2010 and is expected to run for three years.
      DISCUSSION: Some reports have concluded that seroma formation forms part of
      postsurgical inflammation. Steroids are effective against inflammation and
      accumulation of fluid at the surgical site after several types of surgery and
      have also proved valuable in the treatment of seroma formation. In the present
      study, the prophylactic effect of steroids on seroma formation is investigated.
      CONCLUSION: As the incidence of postmastectomy seroma formation is 80%, there is
      a need for improvement in the prophylaxis and treatment of this condition.
      FUNDING: not relevant. TRIAL REGISTRATION: Medicines Agency The EudraCT number
      2009-016650-40 has been issued for your Sponsor's Protocol Code Number 23837.
      Data protection agency J.no. F.750.75-2. The study is perfomed in collaboration
      with the GCP Unit, capital Region, Bispebjerg Hospital under the EudraCT number:
      2009-016650-40.

PMID- 22951194
TI  - Ileoscopy reduces the need for small bowel imaging in suspected Crohn's disease.
AB  - INTRODUCTION: In suspected Crohn's disease (CD), current diagnostic guidelines
      recommend additional small bowel imaging irrespective of the findings at
      ileocolonoscopy. Magnetic resonance imaging enterography (MRE) and computed
      tomography enterography (CTE) are regarded first line imaging techniques and
      should generally precede capsule endoscopy. MATERIAL AND METHODS: This article
      brings together results from a prospective blinded diagnostic study of MRE, CTE,
      capsule endoscopy and faecal calprotectin (fCal) in 93 patients undergoing their
      first diagnostic work-up for CD. RESULTS: In patients with suspected CD, fCal is
      useful for the identification patients without need for colonoscopy or small
      bowel imaging. Patients with an elevated fCal should undergo colonoscopy
      including a persistent attempt to intubate the terminal ileum. CD isolated in the
      upper small bowel is rare, and in patients with a normal ileocolonoscopy or non
      complicated CD in the colon and/or terminal ileum, small bowel imaging provides
      little extra information compared to ileoscopy alone. Small bowel imaging is
      primarily indicated if ileoscopy is not achieved and capsule endoscopy is
      recommended as first line imaging technique. If small bowel stenosis is not ruled
      out, a preceding test with a patency capsule can be performed to avoid capsule
      retention. MRE and CTE are complimentary modalities preferably used in patients
      with stenosis detected at ileocolonoscopy or suspicion of extra-intestinal
      disease complications. CONCLUSION: Our results suggest that a diagnostic approach
      different to that described in the guidelines may be expedient. FUNDING: not
      relevant. TRIAL REGISTRATION: The study was approved by the Ethics Committee of
      Southern Denmark (S-20070072) and the Danish Data Protection Agency (journal
      number: 2007-41-0675). ClinicalTrials.gov identifier: NCT01019460.

PMID- 22951195
TI  - Selected determinants may account for dropout risks among medical students.
AB  - INTRODUCTION: The dropout level from the Danish medical schools is high, but we
      have only little insight into this problem. The purpose of this study was to
      qualify the ongoing discussions concerning dropout. MATERIAL AND METHODS: In this
      retrospective cohort study, relevant variables were extracted from the
      established database of Aarhus University for the 639 students initiating
      medicine studies between 1 January 1999 and 31 December 2000. A multivariate pre
      admission and post-admission model was examined. RESULTS: Of the 639 medical
      students, 20% dropped out. Most students dropped out during their first year. The
      type of admission exam was a strong predictor of dropout in the pre-admission
      model, whereas previous higher education protected against dropout. Obtaining
      leave was a very strong predictor of dropout in the post-admission model, whereas
      high grades protected against dropout. CONCLUSION: The dropout rate has been
      decreasing during the past decade. Young people considering studying medicine
      could be advised to choose natural science subjects in high school, and a number
      of research questions concerning preparedness for medical school are worth
      pursuing. Leave or very low grades during the first and second study years might
      serve as red flags to supervisors. FUNDING: Study research was funded by Aarhus
      University. TRIAL REGISTRATION: Not relevant, register-based research with no
      biological human material cannot be notified to the Danish Committee System. The
      Danish Data Protection Agency allows schools to conduct anonymized, non
      sensitive, educational analyses without notification.

PMID- 22951196
TI  - Promising results after vacuum-assisted wound closure and mesh-mediated fascial
      traction.
AB  - INTRODUCTION: Patients with an open abdomen (OA) present a major challenge to the
      surgeon. High mortality and associated complication rates have been reported
      depending on the specific method of temporary abdominal closure, the primary
      disorder and any co-morbidity. Vacuum-assisted wound closure and mesh-mediated
      fascial traction (VAWCM) is a novel technique recently introduced for late
      fascial closure of the OA. In previous studies, the disease aetiologies were
      mainly vascular and visceral surgical disease and trauma. We report our results
      using VAWCM in a non-trauma patient population treated with an OA due to visceral
      surgical disease. MATERIAL AND METHODS: Medical records of all patients in our
      department treated with VAWCM during the period from 1 August 2009 to 31 May 2011
      were reviewed. All sixteen patients were non-trauma patients. The initial
      treatment was vacuum-assisted closure (VAC) (Abdominal Dressing System KCI, San
      Antonio, Texas, USA). VAWCM treatment was initiated if complete fascial closure
      could not be obtained with VAC. RESULTS: Two patients died of multiple organ
      failure that was not associated with the VAWCM treatment. In one patient,
      treatment was terminated due to a very short life expectancy. We achieved a
      complete fascial closure rate in seven out of 16 patients. One patient had a
      pancreatic fistula at discharge that was not associated with the VAWCM treatment.
      No enteric fistulas occurred. CONCLUSION: It seems that VAWCM can improve the
      rate of complete fascial closure after treatment with OA without increasing the
      mortality or the occurrence of enteric fistula compared with other kinds of
      temporary abdominal closure. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22951197
TI  - Need for more clear parental recommendations regarding foreign body aspiration in
      children.
AB  - INTRODUCTION: Foreign body (FB) aspiration is a common cause of respiratory
      emergency in early childhood and is associated with a high rate of airway
      distress. FB aspiration peaks at the age of 1-2 years. Factors placing children
      at higher risk include incomplete dentition, immature swallowing coordination and
      the tendency to be easily distracted while eating. Symptoms may vary from an un
      affected child to impending airway failure. Mucosal cough receptors often
      accommodate and the child may be asymptomatic when evaluated. MATERIAL AND
      METHODS: Files of children (0-15 years) admitted with suspected FB aspiration
      were reviewed. Patients were included if the FB was confirmed by bronchoscopy.
      RESULTS: Among 136 children undergoing bronchoscopy, a FB was confirmed in 59
      patients. The median age was one year. All children had a history of aspiration
      and in 48% a persistent cough was present at the initial examination. Eleven
      children (19%) had a normal physical examination at admission. Nuts were
      identified in 34% and carrots in 20%. Of the FBs removed, 86% were organic and
      14% were inorganic. Organic FBs were more common in patients younger than three
      years (p < 0.001). CONCLUSION: Parental suspicion of FB aspiration indicates
      acute bronchoscopy in children, even in case of no abnormal findings. The
      completion of the bronchoscopy within 24 hours facilitates the examination and
      reduces the risk of complications. We recommend increased awareness of the
      hazards associated with small crunchy organic food items, especially nuts and
      carrots, given to children under three years of age. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 22951198
TI  - Screening for microalbuminuria in patients with type 2 diabetes is incomplete in
      general practice.
AB  - INTRODUCTION: National Danish guidelines recommend screening for microalbuminuria
      with assessment of urinary albumin/creatinine ratio at least annually in patients
      with type 2 diabetes. To which extent such screening is actually performed is not
      known. MATERIAL AND METHODS: A total of 2,057 patients with type 2 diabetes were
      randomly selected from 64 general practitioners (GPs) from different geographical
      areas of Denmark. Clinical and laboratory data on the individual patients were
      collected through the GPs' electronic medical patient records; particular
      emphasis was given to annual screening for microalbuminuria. RESULTS: The mean
      age of the patients was 66.2 +/- 11.6 years and 58.7% were male. Only 57.2% of
      the patients had been screened for microalbuminuria with any method within the
      preceding 12 months period; of these 76.0% had normo- and 21.0% had
      microalbuminuria, whereas 3.0% had overt proteinuria. In contrast, 97.6% of
      patients had had a minimum of one plasma-creatinine measurement within the past
      year. CONCLUSION: In Danish primary care, screening for microalbuminuria in type
      2 diabetes is insufficiently implemented, whereas renal function is evaluated in
      almost all patients by plasma-creatinine measurements. The importance of
      diagnosing microalbuminuria in patients with type 2 diabetes needs to be
      emphasised. FUNDING: The project has received funding in the form of a research
      grant from Boehringer Ingelheim, Denmark. TRIAL REGISTRATION: not relevant.

PMID- 22951199
TI  - Patients perceive tonsil cancer as a strike at psycho-socially "vital organs".
AB  - INTRODUCTION: Tonsil cancer (TC) is a type of head and neck cancer (HNC) that is
      predominantly associated with infection with human papilloma virus (HPV). In
      Denmark, the incidence of HPV-related HNC has increased fivefold over the past
      three decades. HNC more often affects men than women, and HPV-related HNC tends
      to affect younger age groups than other HNCs. The present study examined the long
      term health-related quality of life (QoL) in patients with TC. MATERIAL AND
      METHODS: A medical anthropological approach was applied using individual
      qualitative interviews with seven former TC patients. The participants included
      men and women who had undergone various treatments, i.e. radiation therapy,
      chemotherapy and operation. Data were analyzed using a narrative methodology.
      RESULTS: Treatment sequelae peaked within the first three months and included
      severe pain in the radiated area, nausea and fatigue. Within this period,
      patients were unable to eat solid food and often had difficulty speaking. Half of
      the participants lost some of their hearing due to radiation. Even two years
      after treatment, most participants had persisting sequelae, mainly xerostomia,
      porous teeth and reduced mobility of the tongue and jaw. Fatigue and difficulties
      eating and communicating, in particular, had a very negative effect on the
      participants' psycho-social QoL. CONCLUSION: This study allowed for a deeper
      understanding of the negative effects of HNC on patients' QoL. These QoL effects
      ought to be included in future considerations of HPV vaccination of boys as well
      as girls. FUNDING: The study was funded by an unrestricted research grant from
      Sanofi Pasteur MSD. TRIAL REGISTRATION: not relevant.

PMID- 22951200
TI  - Vitamin D deficiency is unrelated to type of atrial fibrillation and its
      complications.
AB  - INTRODUCTION: Vitamin D plays an important role in a broad range of organ
      functions, including the cardiovascular system. Only one study has tested the
      association between vitamin D deficiency and arrhythmia and it found no
      association. The aim of the present study was to evaluate the association between
      vitamin D deficiency and the type of atrial fibrillation (AF) and complications
      to AF. MATERIAL AND METHODS: In total, 258 patients were consecutively included
      from March 2009 to February 2011. All in- and out-patients in the Department of
      Cardiology at Hvidovre Hospital were invited to participate, provided they had
      electrocardiographically documented AF. Patients with dementia or terminal
      illness were excluded. 25 hydroxyvitamin D (25 OHD) was measured with a
      chemiluminescence assay (Liaison from DiaSorin, Stillwater, Minnesota, USA).
      RESULTS: No association between vitamin D level and type of AF was found.
      Furthermore, no association between vitamin D deficiency and ischaemic heart
      disease, stroke or acute myocardial infarction was found. Vitamin D deficiency
      was significantly associated with low age (p = 0.02) and gender with a higher
      proportion of females having the optimal level of 25 OHD (p = 0.0005).
      CONCLUSION: Other studies have found a beneficial effect of vitamin D on
      cardiovascular diseases, but we found no association between vitamin D deficiency
      and the type of AF or complications to AF. Further investigation is necessary to
      determine whether vitamin D supplementation improves cardiovascular outcomes in
      patients with AF. FUNDING: The study has received financial support from several
      private and one public fund. TRIAL REGISTRATION: The study was approved by the
      National Ethics Committee (Project-ID: H-C-2009-014).

PMID- 22951201
TI  - The outcome of rectal cancer after early salvage surgery following transanal
      endoscopic microsurgery seems promising.
AB  - INTRODUCTION: Transanal endoscopic microsurgery (TEM) allows locally complete
      resection of early rectal cancer as an alternative to conventional radical
      surgery. In patients with unfavourable post-TEM histology, salvage surgery can be
      performed. The aim of this study was to evaluate the results of early radical
      surgery after TEM for rectal cancer. MATERIAL AND METHODS: From 1997 to 2010, 86
      TEM procedures were performed in 79 patients due to rectal cancer. Early salvage
      surgery was performed in 25 patients. Data were obtained from the patients'
      charts and reviewed retrospectively. Perioperative data and oncological outcome
      were analysed. RESULTS: No patients received preoperative chemotherapy. The
      median time to salvage surgery was 37 days. Five patients underwent laparoscopic
      surgery. The median operative time was 165 min (range: 101-341 min, 95%
      confidence interval (CI): 156-214 min) and the median blood loss 275 ml (range: 0
      1,275 ml, 95% CI: 232-530 ml). The 30-day mortality was 8% (95% CI: 1-19%, n =
      2). Intraoperative perforation occurred in 20% (95% CI: 3-37%, n = 5). The median
      number of harvested lymph nodes was 12 (range: 3-25, 95% CI: 9-14) and the median
      circumferential resection margin (CRM) was 10 mm (range: 0-20 mm, 95% CI: 5-12
      mm). Only one patient (4%, 95%CI: 1-12%) had a positive CRM. The median follow-up
      time was 25 months (range: 3-80 months). There was no local recurrence. Distant
      metastasis occurred in 4% (95% CI: 1-12%, n = 1). CONCLUSION: Early salvage
      surgery after TEM seems to be safe despite a high risk of specimen perforation
      during the operation. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22951202
TI  - Surgeons' motivation for choice of workplace.
AB  - INTRODUCTION: To ensure qualified health care professionals at public hospitals
      in the future, it is important to understand which factors attract health care
      professionals to certain positions. The aim of this study was to explore motives
      for choosing employment at either public or private hospitals in a group of
      Danish surgeons, as well as to examine if organizational characteristics had an
      effect on motivation. MATERIAL AND METHODS: Eight qualitative interviews were
      conducted with surgeons from both public and private hospitals sampled using the
      snowball method. The interviews were based on a semi-structured interview guide
      and analyzed by means of phenomenological theory. RESULTS: Motivational factors
      such as personal influence on the job, the opportunity to provide the best
      possible patient care, challenging work tasks colleagues, and ideological reasons
      were emphasized by the surgeons as important reasons for their choice of
      employment. Motivational factors appeared to be strongly connected to the
      structure of the organization; especially the size of the organization was
      perceived to be essential. It is worth noting that salary, in contrast to the
      general belief, was considered a secondary benefit rather than a primary
      motivational factor for employment. CONCLUSION: The study revealed that
      motivational factors are multidimensional and rooted in organizational structure;
      i.e. organizational size rather than whether the organization is public or
      private is crucial. There is a need for further research on the topic, but it
      seems clear that future health care planning may benefit from taking into account
      the implications that large organizational structures have for the staff working
      within these organizations. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22951203
TI  - Significant improvement in statin adherence and cholesterol levels after acute
      myocardial infarction.
AB  - INTRODUCTION: Not all patients recovering from acute myocardial infarction (AMI)
      are optimally treated with statin, and their adherence to statin treatment may be
      inadequate. We set out to describe changes in statin treatment adherence and
      cholesterol values over time. MATERIAL AND METHODS: Data from two cohorts of AMI
      patients discharged from the Department of Cardiology, Odense University
      Hospital, in 2003 (n = 474, mean age 68 years, 66% males) and 2008 (n = 550, mean
      age 67 years, 69% males) were compared. Based on the number of tablets collected
      at the pharmacy, patients' adherence to statin treatment in a period of two years
      after discharge was analysed. Patients were considered adherent when in
      possession of medication >= 80% of the period. From the day of admission and at
      follow-up, cholesterol values and the relative number of patients with a total
      cholesterol < 4.5 mmol/l were calculated. RESULTS: A significant improvement in
      statin adherence was noted: 42% versus 75% (p < 0.0001). The most significant
      difference was observed in patients >= 80 years, who improved from 25% to 72% (p
      < 0.0001). Furthermore, an overall significant reduction in follow-up cholesterol
      levels was observed: from 4.4 to 4.2 mmol/l (p = 0.003). More-over, an increase
      was observed in the proportion of patients with a follow-up cholesterol value <
      4.5 mmol/l: from 57% to 67% (p = 0.001). The most significant changes were
      demonstrated in patients >= 70 years. CONCLUSION: Over the five-year period from
      2003 to 2008, statin adherence and cholesterol values significantly improved.
      However, room for improvement remains, particularly in younger patients. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22951204
TI  - Antiplatelet effect of aspirin in patients with coronary artery disease.
AB  - Cardiovascular disease is the number one cause of death globally, and
      atherothrombosis is the underlying cause of most cardiovascular events. Several
      studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic
      acid), reduces the risk of cardiovascular events and death. However, it is well
      known that many patients experience cardiovascular events despite treatment with
      aspirin, often termed "aspirin low-responsiveness". This fact has caused
      considerable debate: does biochemical aspirin low-responsiveness have prognostic
      value? Can low-responders be reliably identified? And if so, should
      antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug
      response merely a result of low compliance? Compliance should be carefully
      optimised, before evaluating the pharmacological effect of a drug. It is well
      known that cardiovascular disease is multifactorial, and, therefore, total risk
      reduction is not feasible. Aetiological factors to the variable platelet
      inhibition by aspirin seem to include genetic factors, pharmacological
      interactions, smoking, diabetes mellitus, and increased platelet turnover. It is
      a captivating thought that antiplatelet therapy may be improved by individually
      tailored therapy based on platelet function testing. Ongoing studies are
      challenging the current one-size-fits-all dosing strategy, but the preceding
      evaluation of platelet function assays has not been adequate. The overall
      objective of this thesis was to evaluate the reproducibility of and aggreement
      between a number of widely used platelet function tests and to explore the
      importance of platelet turnover for the antiplatelet effect of aspirin in
      patients with coronary artery disease. In the intervention studies (studies 1, 3,
      and 4), optimal compliance was confirmed by measurements of serum thromboxane,
      which is the most sensitive assay to confirm compliance with aspirin. In study 1,
      platelet function tests widely used to measure the antiplatelet effect of aspirin
      were evaluated in healthy individuals and patients with coronary artery disease.
      Pharmaco-specific metabolites were measured in urine and serum to investigate the
      pharmacodynamic effect of aspirin and to enable the comparison with the more
      global tests of platelet function. Based on repeated duplicate measurements, we
      evaluated the reproducibility of each test. We found that reproducibility of the
      classical reference method was not impressive and that the newer, so-called point
      of-care tests differed markedly on reproducibility. With coefficients of
      variation of about 3%, the VerifyNow Aspirin test was clearly the most
      reproducible test - even after correction of the official scale, which begins at
      about 350 aspirin reaction units and, therefore, results in artificially low
      coefficients of variation. Among the platelet function tests investigated,
      Multiplate was most sensitive for aspirin treatment. In study 2 we performed the
      hitherto largest study of newly released, immature platelets as a marker of
      platelet turnover. The study population included healthy individuals, patients
      with stable coronary artery disease, and patients with acute coronary syndromes.
      The main finding was an increased fraction of immature platelets in patients with
      ST-segment myocardial infarction, indicating an increased platelet turnover.
      Smoking and type 2 diabetes were identified as independent determinants of
      platelet turnover. In study 3 we explored the relationship between platelet
      turnover and the antiplatelet effect of aspirin in patients with stable coronary
      artery disease. The study results support the hypothesis that an increased
      platelet turnover reduces the antiplatelet effect of aspirin. The main findings
      were: 1) platelet turnover correlated with platelet aggregation measured by
      Multiplate and with sP-selectin, a marker of platelet activation. 2) Patients
      with diabetes mellitus type 2 had reduced antiplatelet effect of aspirin compared
      with patients without diabetes. 3) Widely used platelet function tests differ
      with respect to dependence on platelet parameters, including platelet count. 4)
      Smoking, diabetes mellitus type 2, and thrombopoietin were identified as
      independent determinants of platelet turnover. 5) The relative fraction of
      immature platelets has been employed in most previous studies, but in stable
      patients the absolute immature platelet count does not seem dependent on the
      total platelet count, and it has a stronger correlation with both platelet
      activation measured by sP-selectin and with platelet aggregation during treatment
      with aspirin. In study 4 we investigated platelet turnover and the antiplatelet
      effect of aspirin in a nested case-control study on patients with previous
      definite stent thrombosis. Patients with stent thrombosis were compared with
      patients without stent thrombosis, with whom they were matched at a 1:2 ratio
      with respect to risk factors for stent thrombosis: age, sex, stent type, and
      indication for percutaneous coronary intervention. The study showed that patients
      with previous stent thrombosis have reduced antiplatelet effect of aspirin and a
      tendency towards increased platelet turnover. In conclusion, widely used platelet
      function tests markedly differ on reproducibility, and the agreement between
      tests is relatively poor. An increased platelet turnover as suggested by the
      presence of newly formed immature platelets is important for the antiplatelet
      effect of aspirin, and, perhaps also for the development of acute coronary
      thrombosis. In the future, individually tailored antiplatelet therapy may
      potentially improve the benefit-risk ratio of antiplatelet therapy.

PMID- 22951205
TI  - The use of secondary medical prevention after primary vascular reconstruction:
      studies on usage and effectiveness.
AB  - Peripheral arterial disease (PAD) is a common manifestation of symptomatic
      atherosclerosis that leads to a significantly elevated risk of cardiovascular
      events, including major limb loss, myocardial infarction, stroke and death. The
      prevalence proportions of PAD increase dramatically with age and appear to
      progress more aggressively in women than in men. Several studies have indicated
      that the use of secondary medical prevention is generally insufficient among PAD
      patients. However, current national and international guidelines recommend lipid
      lowering and anti-platelet therapy, supplemented with aggressive blood pressure
      lowering treatment. We aimed to determine whether there were age-, gender-,
      geography or time related differences in the use of secondary medical prevention,
      following primary vascular reconstruction. We also sought to describe the
      prognoses for the same population, according to the association between the use
      of ACE/ATII inhibitors (angiotensin-converting enzyme inhibitors and angiotensin
      II receptor antagonists) or beta blockers and clinical outcomes (all cause
      mortality, myocardial infarction, stroke, major amputation and/or recurrent
      vascular surgery) in a population-based, long-term follow-up study. We
      established a data base by linking four population based administrative and
      health-care registries. All Danish patients undergoing primary vascular surgical
      reconstruction due to atherosclerotic disease between 1997 and 2007 were included
      and identified in the Danish Vascular Registry; a total of 20,761 patients were
      followed during a median of 582 days (range of 30 to 4,379 days). Data regarding
      all prescriptions filled by the study population were obtained from the Medical
      Registry of the Danish Medicines Agency. Study I: Age- and gender-related
      differences. We found moderate to low use of secondary medical prevention.
      However, this use has increased in recent years and the age- and gender-related
      differences in use have been reduced or eliminated. Study II: Geographic or time
      related differences. The use of evidence-based secondary medical prevention,
      especially lipid-lowering drugs, increased substantially over time, regardless of
      socio-demographic and clinical factors. No substantial differences in
      pharmacological use according to location of residence were observed. Study III:
      Use of ACE/ATII and prognosis. We found the use of ACE inhibitors to be
      associated with lower all cause mortality but also an increased long-term risk of
      recurrent vascular reconstruction and myocardial infarction. Study IV: Use of
      beta blockers and prognosis. We found beta blocker use to be associated with a
      lower risk of major amputation, but also an increased risk of new myocardial
      infarction and stroke. No association were found regarding all cause mortality or
      the risk of recurrent vascular surgery. In conclusion, the use of secondary
      medical prevention following primary vascular surgery (between 1996 and 2006 in
      Denmark) shifted towards a more evidence-based treatment, as reduction in age-,
      gender- and geography related differences were observed early in the study
      period. However, recommendations for the current clinical guidelines suggest that
      additional improvement can be made. The treatment of hypertension in PAD patients
      is complex, and our results are also complex but indicate that ACE/ATII and beta
      blockers are safe for use in symptomatic PAD patients.

PMID- 22951206
TI  - Vitrification in human and domestic animal embryology: work in progress.
AB  - According to the analysis of papers published in major international journals,
      rapidly increasing application of vitrification is one of the greatest
      achievements in domestic animal and especially human embryology during the first
      decade of our century. This review highlights factors supporting or hampering
      this progress, summarises results achieved with vitrification and outlines future
      tasks to fully exploit the benefits of this amazing approach that has changed or
      will change many aspects of laboratory (and also clinical) embryology. Supporting
      factors include the simplicity, cost efficiency and convincing success of
      vitrification compared with other approaches in all species and developmental
      stages in mammalian embryology, while causes that slow down the progress are
      mostly of human origin: inadequate tools and solutions, superficial teaching,
      improper application and unjustified concerns resulting in legal restrictions.
      Elimination of these hindrances seems to be a slower process and more demanding
      task than meeting the biological challenge. A key element of future progress will
      be to pass the pioneer age, establish a consensus regarding biosafety
      requirements, outline the indispensable features of a standard approach and
      design fully-automated vitrification machines executing all phases of the
      procedure, including equilibration, cooling, warming and dilution steps.

PMID- 22951207
TI  - Multidisciplinary collaboration in primary care: through the eyes of patients.
AB  - Managing chronic illness is highly complex and the pathways to access health care
      for the patient are unpredictable and often unknown. While multidisciplinary care
      (MDC) arrangements are promoted in the Australian primary health care system,
      there is a paucity of research on multidisciplinary collaboration from patients'
      perspectives. This exploratory study is the first to gain an understanding of the
      experiences, perceptions, attitudes and potential role of people with chronic
      illness (asthma) on the delivery of MDC in the Australian primary health care
      setting. In-depth semi-structured interviews were conducted with asthma patients
      from Sydney, Australia. Qualitative analysis of data indicates that patients are
      significant players in MDC and their perceptions of their chronic condition,
      perceived roles of health care professionals, and expectations of health care
      delivery, influence their participation and attitudes towards multidisciplinary
      services. Our research shows the challenges presented by patients in the delivery
      and establishment of multidisciplinary health care teams, and highlights the need
      to consider patients' perspectives in the development of MDC models in primary
      care. 

PMID- 22951209
TI  - Screening for abdominal aortic aneurysm: does it affect men's quality of life?
AB  - A prospective study investigated the psychological wellbeing and quality of life
      of older rural men after a community-based screening for abdominal aortic
      aneurysm (AAA). Five hundred and sixteen men aged 65-74 years attended the
      screening program; 53 had an abnormal aorta detected. These and a subsample of
      men with a normal aorta were followed up 6 months post-screening. All men
      completed a pre-screening questionnaire including the Medical Outcomes Short Form
      36v 2 (MOSF36) and Hospital Anxiety and Depression Scale (HADS). Six months after
      screening all 53 men with an abnormal and 130 with a normal aorta were sent a
      questionnaire including MOSF36 and HADS. Baseline and 6 month scores for both
      MOSF36 and HADS scores were compared between the two groups and within each
      group. Baseline scores for both MOSF36 and HADS were not significantly different
      between men who were subsequently diagnosed with an abnormal aorta and those with
      a normal aorta. After 6 months there was no difference in HADS scores but a
      significant increase in the MOSF36 dimension of general health. Those with a
      normal aorta reported better general health, social functioning and greater
      freedom from bodily pain. AAA screening appears highly acceptable to men in the
      target age group and future research should focus on implementation, cost
      effectiveness and collateral benefits of AAA screening.

PMID- 22951208
TI  - Metagenomics and metatranscriptomics: windows on CF-associated viral and
      microbial communities.
AB  - BACKGROUND: Samples collected from CF patient airways often contain large amounts
      of host-derived nucleic acids that interfere with recovery and purification of
      microbial and viral nucleic acids. This study describes metagenomic and
      metatranscriptomic methods that address these issues. METHODS: Microbial and
      viral metagenomes, and microbial metatranscriptomes, were successfully prepared
      from sputum samples from five adult CF patients. RESULTS: Contaminating host DNA
      was dramatically reduced in the metagenomes. Each CF patient presented a unique
      microbiome; in some Pseudomonas aeruginosa was replaced by other opportunistic
      bacteria. Even though the taxonomic composition of the microbiomes is very
      different, the metabolic potentials encoded by the community are very similar.
      The viral communities were dominated by phages that infect major CF pathogens.
      The metatranscriptomes reveal differential expression of encoded metabolic
      potential with changing health status. CONCLUSIONS: Microbial and viral
      metagenomics combined with microbial transcriptomics characterize the dynamic
      polymicrobial communities found in CF airways, revealing both the taxa present
      and their current metabolic activities. These approaches can facilitate the
      development of individualized treatment plans and novel therapeutic approaches.

PMID- 22951210
TI  - Basic gait analysis based on continuous wave radar.
AB  - A gait analysis method based on continuous wave (CW) radar is proposed in this
      paper. Time-frequency analysis is used to analyze the radar micro-Doppler echo
      from walking humans, and the relationships between the time-frequency spectrogram
      and human biological gait are discussed. The methods for extracting the gait
      parameters from the spectrogram are studied in depth and experiments on more than
      twenty subjects have been performed to acquire the radar gait data. The gait
      parameters are calculated and compared. The gait difference between men and women
      are presented based on the experimental data and extracted features. Gait
      analysis based on CW radar will provide a new method for clinical diagnosis and
      therapy.

PMID- 22951211
TI  - Kinematic coupling relationships exist between non-adjacent segments of the foot
      and ankle of healthy subjects.
AB  - Pathologies of foot and ankle structures affect the kinematics at the site of the
      impaired structure but also influence kinematics elsewhere in the foot and ankle.
      An understanding of kinematic coupling relationships in the foot could provide
      insight into mechanisms that explain differences in foot and ankle kinematics
      between healthy and pathological subjects. The aim of this study was to explore
      foot and ankle kinematic coupling relationships between adjacent and non-adjacent
      segments of healthy subjects and evaluate individual variability of and effect of
      walking speed on these relationships. Gait of 14 subjects was recorded at
      comfortable and two slower walking speeds to assess individual foot kinematics
      during stance phase. A qualitative evaluation of the coupling relationships was
      made using angle-angle plots to determine their consistency, i.e. changes in
      movement direction of each segment occurred at the same time and the plot
      returned along the same line after the turning point. The Pearson correlation
      coefficient of determination (R(2)) was used to provide a quantitative evaluation
      of coupling. Individual variability was assessed with the coefficient of
      variation (CV). The Friedman-test was used to test the effect of walking speed.
      Consistent coupling relationships were observed between hindfoot in/eversion and
      hallux plantar/dorsiflexion (R(2) 0.7, CV 0.2), between hindfoot in/eversion and
      forefoot ab/adduction (R(2) 0.5, CV 0.3) and between leg rotation and midfoot
      collapse/elevation (R(2) 0.5, CV 0.4). Less or non-consistent coupling
      relationships were observed between the other studied segments. Walking speed
      significantly influenced coupling relationships between hindfoot and midfoot.

PMID- 22951212
TI  - Structural analysis and cellular localization of polyunsaturated C27 hydrocarbons
      in the marine dinoflagellate, Pyrocystis lunula (Dinophyceae).
AB  - A neutral lipid fraction obtained from two strains of the permanently sheathed
      dinoflagellate, Pyrocystis lunula, was found to contain three polyunsaturated C27
      hydrocarbons as abundant lipid components. A combination of mass spectrometry
      techniques was used to identify these compounds as n-heptacosa-3,6,9,12,15,18
      hexaene (C27:6), approx. 0.7 ng/sheathed cell), n-heptacosa-3,6,9,12,15,18,21
      heptaene (C27:7), approx. 2 ng/sheathed cell), and n-heptacosa
      3,6,9,12,15,18,21,24-octaene (C27:8), approx. 2 ng/sheathed cell).
      Polyunsaturated C21, C23, and C25 hydrocarbons were also found at lesser amounts
      of approximately 0.2-0.5 ng/sheathed cell. Fluorescent microscopy revealed Nile
      red staining in both the vegetative cell and structures within the outer sheath
      surrounding the cell. These hydrocarbons were not present in two other species of
      Pyrocystis, P. fusiformis and P. noctiluca. Although their function(s) is not
      known, previous studies have shown and hypothesized that similar hydrocarbons
      function in carbon storage, buoyancy regulation, or signaling.

PMID- 22951213
TI  - Mendelian inheritance pattern and high mutation rates of microsatellite alleles
      in the diatom Pseudo-nitzschia multistriata.
AB  - The diatom Pseudo-nitzschia multistriata exhibits a diplontic life cycle composed
      of an extensive phase of vegetative cell division and a brief phase of sexual
      reproduction. To explore genotypic stability, we genotyped seven polymorphic
      microsatellite loci in 26 monoclonal strains over 3-16 months in a culture
      maintenance regime. Moreover, to assess inheritance patterns of the
      microsatellite alleles, we genotyped 246 F1 strains resulting from four mating
      experiments between parental strains of know genotype. Results generally
      conformed expectations according to Mendelian inheritance patterns, but
      deviations were detected indicating mutations during sexual reproduction. A total
      of forty-two mutations were detected in the clonal cultures over time.
      Microsatellites with more core-repeats accumulated mutations faster. The mutation
      rate varied significantly across loci and strains. A binomial mass function and a
      computer simulation showed that the mutation rate was significantly higher during
      the first months of culture (MU~3*10(-3) per locus per cell division) and
      decreased to MU~1*10(-3) in the strains kept for 16 months. Our results suggest
      that genetic mutations acquired in both the vegetative phase and sexual
      reproduction add to the allelic diversity of microsatellites, and hence to the
      genotypic variation present in a natural population.

PMID- 22951214
TI  - Effect of resveratrol on oxygen consumption by Philasterides dicentrarchi, a
      scuticociliate parasite of turbot.
AB  - The phytoalexin resveratrol (RESV) displays antiparasitic activity against
      Philasterides dicentrarchi, a scuticociliate pathogen of turbot, and causes
      oxidative stress, inhibition of antioxidant enzyme activity and morphological
      alterations in the parasite mitochondria. In this study, we analysed the
      mitochondrial biology of P. dicentrarchi and assessed the effect of RESV on
      mitochondrial metabolism. We found that RESV caused dose-dependent inhibition of
      mitochondrial electron transport and O2 consumption in ciliates permeabilized
      with digitonin. Although the RESV molecule has a high capacity for antiradical
      and antioxidant activity, it induced a high level of pro-oxidant activity against
      the ciliate, thus causing a significant increase in intracellular ROS production.
      The increased ROS production was accompanied by mitochondrial collapse and
      dysfunction of mitochondrial membrane potential (DeltaPsim) and by a significant
      increase in intracellular Ca+2 levels. RESV inhibited parasite growth in a
      similar way to antimycin A, an inhibitor of mitochondrial electron transport and
      ROS generator. The findings confirm the mitochondria as a target in the potential
      development of effective antiparasitic treatments.

PMID- 22951215
TI  - Apparent low ability of liver and muscle to adapt to variation of dietary
      carbohydrate:protein ratio in rainbow trout (Oncorhynchus mykiss).
AB  - The rainbow trout (Oncorhynchus mykiss) exhibits high dietary amino acid
      requirements and an apparent inefficiency to use dietary carbohydrates. Using
      this species, we investigated the metabolic consequences of long-term high
      carbohydrates/low protein feeding. Fish were fed two experimental diets
      containing either 20% carbohydrates/50% proteins (C20P50), or high levels of
      carbohydrates at the expense of proteins (35% carbohydrates/35% proteins-
      C35P35). The expression of genes related to hepatic and muscle glycolysis
      (glucokinase (GK), pyruvate kinase and hexokinase) illustrates the poor
      utilisation of carbohydrates irrespective of their dietary levels. The increased
      postprandial GK activity and the absence of inhibition of the gluconeogenic
      enzyme glucose-6-phosphatase activity support the hypothesis of the existence of
      a futile cycle around glucose phosphorylation extending postprandial
      hyperglycaemia. After 9 weeks of feeding, the C35P35-fed trout displayed lower
      body weight and feed efficiency and reduced protein and fat gains than those fed
      C20P50. The reduced activation of eukaryotic translation initiation factor 4-E
      binding protein 1 (4E-BP1) in the muscle in this C35P35 group suggests a
      reduction in protein synthesis, possibly contributing to the reduction in N gain.
      An increase in the dietary carbohydrate:protein ratio decreased the expression of
      genes involved in amino acid catabolism (serine dehydratase and branched-chain
      alpha-keto acid dehydrogenase E1alpha and E1beta), and increased that of
      carnitine palmitoyltransferase 1, suggesting a higher reliance on lipids as
      energy source in fish fed high-carbohydrate and low-protein diets. This probably
      also contributes to the lower fat gain. Together, these results show that
      different metabolic pathways are affected by a high-carbohydrate/low-protein diet
      in rainbow trout.

PMID- 22951216
TI  - The clinical relevance of IgA anticardiolipin and IgA anti-beta2 glycoprotein I
      antiphospholipid antibodies: a systematic review.
AB  - The antiphospholipid syndrome (APS) is diagnosed in patients with thromboembolic
      events and/or pregnancy loss in the presence of persistent laboratory evidence
      for antiphospholipid antibodies (aPL). Diagnostic tests for the detection of
      antiphospholipid antibodies include laboratory assays that detect anticardiolipin
      antibodies, lupus anticoagulants, and anti-beta(2)-glycoprotein I antibodies.
      Most studies on aPL have mainly focused on the estimation of the IgG and IgM
      isotypes, with only a few studies reporting on the pathogenic significance of IgA
      aPL. In this review we aimed to summarize and analyze the evidence published in
      the literature on the prevalence and the clinical significance of IgA aPL.

PMID- 22951217
TI  - beta-Nerve growth factor is a major component of alpaca seminal plasma and
      induces ovulation in female alpacas.
AB  - Ovulation in camelids is induced by an unidentified protein in the seminal plasma
      of the male termed 'ovulation-inducing factor'. This protein has been reported to
      be a 14-kDa protein under reducing conditions, which, when purified from seminal
      plasma, induces ovulation in llamas. The identification of this protein and
      investigation of its potential to induce ovulation in camelids may aid the
      development of protocols for the induction of ovulation. In the present study,
      alpaca seminal plasma proteins were separated using one-dimensional sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and the most abundant protein
      of 14 kDa was identified as beta-nerve growth factor (beta-NGF) by liquid
      chromatography mass spectrometry. Female alpacas (n = 5 per group) were given
      intramuscular injections of: (1) 1 mL of 0.9% saline; (2) 4 ug buserelin, a
      gonadotrophin-releasing hormone agonist; (3) 2 mL alpaca seminal plasma; or (4)
      1mg human beta-NGF. Ovulation was detected by transrectal ultrasonography 8 days
      after treatment and confirmed by plasma progesterone concentrations. Ovulation
      occurred in 0%, 80%, 80% and 80% of animals treated with saline, buserelin,
      seminal plasma and beta-NGF, respectively. Treatment type did not affect the
      diameter of the corpus luteum, but plasma progesterone concentrations were lower
      in saline-treated animals than in the other treatment groups owing to the lack of
      a corpus luteum. The present study is the first to identify the ovulation
      inducing factor protein in alpacas. beta-NGF successfully induces ovulation in
      alpacas and this finding may lead to new methods for the induction of ovulation
      in camelids.

PMID- 22951218
TI  - Small and long non-coding RNAs in cardiac homeostasis and regeneration.
AB  - Cardiovascular diseases and in particular heart failure are major causes of
      morbidity and mortality in the Western world. Recently, the notion of promoting
      cardiac regeneration as a means to replace lost cardiomyocytes in the damaged
      heart has engendered considerable research interest. These studies envisage the
      utilization of both endogenous and exogenous cellular populations, which undergo
      highly specialized cell fate transitions to promote cardiomyocyte replenishment.
      Such transitions are under the control of regenerative gene regulatory networks,
      which are enacted by the integrated execution of specific transcriptional
      programs. In this context, it is emerging that the non-coding portion of the
      genome is dynamically transcribed generating thousands of regulatory small and
      long non-coding RNAs, which are central orchestrators of these networks. In this
      review, we discuss more particularly the biological roles of two classes of
      regulatory non-coding RNAs, i.e. microRNAs and long non-coding RNAs, with a
      particular emphasis on their known and putative roles in cardiac homeostasis and
      regeneration. Indeed, manipulating non-coding RNA-mediated regulatory networks
      could provide keys to unlock the dormant potential of the mammalian heart to
      regenerate. This should ultimately improve the effectiveness of current
      regenerative strategies and discover new avenues for repair. This article is part
      of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of
      Differentiation, Metabolism and Contraction.

PMID- 22951220
TI  - Extracellular ATP induces cell death in human intestinal epithelial cells.
AB  - BACKGROUND: Extracellular ATP is an endogenous signaling molecule released by
      various cell types and under different stimuli. High concentrations of ATP
      released into the extracellular medium activate the P2X7 receptor in most
      inflammatory conditions. Here, we seek to characterize the effects of ATP in
      human intestinal epithelial cells and to evaluate morphological changes in these
      cells in the presence of ATP. METHODS: We treated human intestinal epithelial
      cells with ATP and evaluated the effects of this nucleotide by scanning and
      transmission electron microscopy analysis and calcium measurements. We used flow
      cytometry to evaluate apoptosis. We collected human intestinal explants for
      immunohistochemistry, apoptosis by the TUNEL approach and caspase-3 activity
      using flow cytometry analyses. We also evaluated the ROS production by flow
      cytometry and NO secretion by the Griess technique. RESULTS: ATP treatment
      induced changes characteristic of cell death by apoptosis and autophagy but not
      necrosis in the HCT8 cell line. ATP induced apoptosis in human intestinal
      explants that showed TUNEL-positive cells in the epithelium and in the lamina
      propria. The explants exhibited a significant increase of caspase-3 activity when
      the colonic epithelial cells were incubated with IFN-gamma followed by ATP as
      compared to control cells. In addition, it was found that antioxidants were able
      to inhibit both the ROS production and the apoptosis induced by ATP in epithelial
      cells. GENERAL SIGNIFICANCE: The activation of P2X7 receptors by ATP induces
      apoptosis and autophagy in human epithelial cells, possibly via ROS production,
      and this effect might have implications for gut inflammatory conditions.

PMID- 22951219
TI  - Impact of titin isoform on length dependent activation and cross-bridge cycling
      kinetics in rat skeletal muscle.
AB  - The magnitude of length dependent activation in striated muscle has been shown to
      vary with titin isoform. Recently, a rat that harbors a homozygous autosomal
      mutation (HM) causing preferential expression of a longer, giant titin isoform
      was discovered (Greaser et al. 2005). Here, we investigated the impact of titin
      isoform on myofilament force development and cross-bridge cycling kinetics as
      function of sarcomere length (SL) in tibialis anterior skeletal muscle isolated
      from wild type (WT) and HM. Skeletal muscle bundles from HM rats exhibited
      reductions in passive tension, maximal force development, myofilament calcium
      sensitivity, maximal ATP consumption, and tension cost at both short and long
      sarcomere length (SL=2.8MUm and SL=3.2MUm, respectively). Moreover, the SL
      dependent changes in these parameters were attenuated in HM muscles.
      Additionally, myofilament Ca(2+) activation-relaxation properties were assessed
      in single isolated myofibrils. Both the rate of tension generation upon Ca(2+)
      activation (kACT) as well as the rate of tension redevelopment following a length
      perturbation (kTR) were reduced in HM myofibrils compared to WT, while relaxation
      kinetics were not affected. We conclude that presence of a long isoform of titin
      in the striated muscle sarcomere is associated with reduced myofilament force
      development and cross-bridge cycling kinetics, and a blunting of myofilament
      length dependent activation. This article is part of a Special Issue entitled:
      Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and
      Contraction.

PMID- 22951221
TI  - Novel aminobenzyl-acetamidine derivative modulate the differential regulation of
      NOSs in LPS induced inflammatory response: role of PI3K/Akt pathway.
AB  - BACKGROUND: Previous reports suggest that NO may contribute to the
      pathophysiology of septic shock. Recently, we have synthesized and characterized
      a series of benzyl- and dibenzyl derivative of N-(3-aminobenzyl)acetamidine, a
      potent and selective inhibitor of iNOS, in vitro assay. We evaluated the
      molecular mechanisms by which these compounds are involved in the regulation of
      NOSs expression. METHODS: H9c2 cells were stimulated with lipopolysaccharide
      (LPS) in the presence or absence of acetamidine-derivative. The NOSs mRNA and
      protein, and activation of signaling pathways (Akt and NF-kappaB) were assayed.
      RESULTS: The induction of endotoxic shock in H9c2 with LPS caused an increase of
      inducible NOS and a down-regulation of constitutive NOS. The molecular mechanism
      involved in the modulation of NOSs expression in H9c2 cells upon LPS stimulation
      resulted in the modification of the redox state responsible for NF-kB nuclear
      translocation via NIK -IKKalpha/beta-IkBalpha, simultaneously to the inactivation
      of the PI3K/Akt pathway. The compounds acted as an anti-inflammatory modulator.
      CONCLUSION: These results suggest that LPS regulates the opposite NOS expression
      in H9c2 cells by modifying the redox state of these cells responsible for the NF
      kB nuclear translocation via NIK-IKKalpha/beta-IkBalpha, simultaneous to the
      inactivation of the PI3K/Akt pathway. The new molecule acts as an anti
      inflammatory modulator in LPS-induced inflammation in H9c2 cells by the
      restoration of eNOS and nNOS expressions, mechanistically involving the PI3K/Akt
      pathway. GENERAL SIGNIFICANCE: This study delineates the underlying mechanisms of
      opposite NOSs expression in H9c2 cells stimulated with LPS.

PMID- 22951222
TI  - The composition of carcass volatile profiles in relation to storage time and
      climate conditions.
AB  - After death organisms are decomposed by a variety of enzymes and microorganisms.
      The decay is typically accompanied by the emission of a plethora of volatile
      organic compounds responsible for the unpleasant odour of a carcass and thus, for
      the attraction of necrophagous insects. The composition of carcass-related odour
      profiles strongly depends on the composition of macro-nutrients like fat,
      carbohydrates, and particularly protein, as well as on the presence of oxygen
      which influences the community of microorganisms colonising the corpse. The
      impact of abiotic factors like temperature and humidity on carcass-related
      volatile emission is less well understood although these parameters are known to
      have a strong impact on the growth of microorganisms. In the present study we
      investigated the volatile succession released from dead mice stored for one, ten
      and 30 days under warm/hot (wh, 22 degrees C/80-90% RH) or cold/dry (cd, 12
      degrees C/40-60% RH) climate conditions. We identified 51 typical carcass
      volatiles by coupled gas chromatography-mass spectrometry and analysed the
      volatile profiles by multivariate statistical methods to find compounds
      characterising the different stages. Dead mice stored under wh conditions
      released volatiles much faster, in higher amounts, and in a greater diversity
      than those stored under cd conditions. The relatively low amount of sulphur
      chemicals released under cd conditions were most striking. The results are
      discussed with respect to their possible applicability in forensic science and
      insect ecology studies.

PMID- 22951223
TI  - Recycling ground granulated blast furnace slag as cold bonded artificial
      aggregate partially used in self-compacting concrete.
AB  - Ground granulated blast furnace slag (GGBFS), a by-product from iron industry,
      was recycled as artificial coarse aggregate through cold bonding pelletization
      process. The artificial slag aggregates (ASA) replaced partially the natural
      coarse aggregates in production of self-compacting concrete (SCC). Moreover, as
      being one of the most widely used mineral admixtures in concrete industry, fly
      ash (FA) was incorporated as a part of total binder content to impart desired
      fluidity to SCCs. A total of six concrete mixtures having various ASA replacement
      levels (0%, 20%, 40%, 60%, and 100%) were designed with a water-to-binder (w/b)
      ratio of 0.32. Fresh properties of self-compacting concretes (SCC) were observed
      through slump flow time, flow diameter, V-funnel flow time, and L-box filling
      height ratio. Compressive strength of hardened SCCs was also determined at 28
      days of curing. It was observed that increasing the replacement level of ASA
      resulted in decrease in the amount of superplasticizer to achieve a constant
      slump flow diameter. Moreover, passing ability and viscosity of SCC's enhanced
      with increasing the amount of ASA in the concrete. The maximum compressive
      strength was achieved for the SCC having 60% ASA replacement.

PMID- 22951224
TI  - Self-cleaning, maintenance-free aerosol filter by non-thermal plasma at
      atmospheric pressure.
AB  - Two lab-scale self-cleaning filters based on dielectric barrier discharges in air
      at atmospheric pressure have been developed and tested. Experimental results on
      aerosol removal by charging and electro-collection are presented versus plasma
      and hydrodynamic parameters for monodisperse aerosol from 20 nm to 1.2 MUm. For
      classical atmospheric aerosol, the average mass and number filtration
      efficiencies exceed 95% and 87%, respectively in the most penetrating size range
      (100-700 nm). The frequency of the applied voltage controls the amplitude of the
      oscillation of charged particle and can be adjusted to favour either filtration
      or cleaning. Low frequency (1 kHz) is suitable for electro-collection, while high
      frequency (60 kHz) is favourable for filter cleaning. Electrical characterization
      and filter efficiency are two indicators of the filter loading. The durations of
      both filtration step at maximal efficiency and cleaning step depends on the
      deposited mass, the surface input power and subsequent dielectric surface
      temperature.

PMID- 22951225
TI  - The effect of co-impregnated acids on the performance of Zn-based broad spectrum
      respirator carbons.
AB  - Impregnated activated carbons (IACs) that are used in multi-gas respirator
      applications usually contain copper and/or zinc impregnants. Co-impregnating with
      properly selected acids can improve the distribution of the metallic impregnant
      on the carbon and improve the gas adsorption capacity of the IAC. In this work a
      comparative study of some common acids co-impregnated with a zinc nitrate
      (Zn(NO(3))(2)) precursor is performed. The IACs were heated in an inert
      atmosphere at temperatures which promoted the thermal decomposition of
      Zn(NO(3))(2) to zinc oxide (ZnO). The gas adsorption properties of the IACs were
      tested using ammonia (NH(3)), sulphur dioxide (SO(2)) and hydrogen cyanide (HCN)
      challenge gases. Powder X-ray diffraction (XRD) was used to identify the
      impregnant species present after heating and to study impregnant distribution.
      Gravimetric analysis was used to determine the impregnant loading, and help to
      identify the impregnant species after heating. The interactions between the co
      impregnated acid and Zn(NO(3))(2) precursor during heating are discussed. The
      relationship between impregnant species and gas adsorption capacity is discussed.

PMID- 22951226
TI  - Emergence of New Delhi metallo-beta-lactamase in Jerusalem, Israel.

PMID- 22951227
TI  - Can pollination niches facilitate plant coexistence?
AB  - The question of why there are so many plant species needs two kinds of answer: an
      explanation for the origin of plant species, and an explanation for how they can
      coexist. Pollinators are often implicated in the origin of plant species because
      adaptation to different modes of pollination can drive divergence in floral
      traits and bring about reproductive isolation. However, very few studies have
      attempted to answer the next question: 'Can plant species that differ only in
      their mode of pollination coexist?' Fragmentary evidence supports the idea that
      intraspecific competition for pollination resources can limit population growth
      rate, thus allowing the coexistence of species that use different pollinators, or
      the same pollinators at different times.

PMID- 22951228
TI  - Apoptotic responses of Carassius auratus lymphocytes to nodularin exposure in
      vitro.
AB  - Nodularin, a metabolite of Nodularin spumigena, is widely detected in water
      blooms worldwide and causes serious negative effects on fish. The apoptosis
      related cytotoxic effects and mechanisms of nodularin on Carassius auratus
      lymphocytes were investigated. Transmission electron microscopy results showed
      that nodularin-treated lymphocytes display a series of morphological changes,
      including condensed cytoplasm, nuclear chromatin agglutination and
      marginalization. DNA fragmentation was verified by the DNA-ladder and formation
      of sub-G1 DNA peaks. These cell characteristics confirmed the occurrence of
      apoptosis in lymphocytes. Flow cytometric results showed that the percentages of
      apoptotic cells incubated with 1, 5, 10, and 100 MUg/L nodularin for 12 h reached
      15.76%, 17.36%, 20.34% and 44.21%, respectively; controls showed low rates of
      apoptosis (2.4%). The mechanism of apoptosis induced by nodularin was determined,
      and results showed that nodularin exposure caused a significant increase in
      intracellular reactive oxygen species (ROS), loss of mitochondrial transmembrane
      potential in a dose-dependent manner, upregulation of intracellular Ca2+,
      downregulation of Bcl-2 and upregulation of Bax expression at the mRNA and
      protein levels, and activation of caspase-3 and caspase-9 without caspase-8. In
      summary, all the results suggest that nodularin induces lymphocyte apoptosis via
      the mitochondrial apoptotic pathway and destroys the immune response of fish.

PMID- 22951229
TI  - Biostatic activity of piscine serum and mucus on myxozoan fish infective stages.
AB  - Since the basis of host specificity in Myxozoa, i.e. the differential disposition
      and extinction of erroneously penetrated myxozoan infective stages in non
      susceptible fish hosts, remains puzzling, we aimed to explore the role of the
      innate immune system in this issue. In a comparative incubation challenge of
      actinospore sporoplasms of the freshwater parasite species Myxobolus cerebralis,
      Henneguya nuesslini and Myxobolus pseudodispar to isolates of host and non-host
      muci and blood sera, we measured cellular disintegration proportions and times by
      means of a double staining viability assay utilizing fluorescent dyes. After
      their activation, emerging primary and secondary sporoplasm cells were evaluated
      microscopically for physical integrity and onset of cell death due to exposure.
      Impairment by any mucus used was not detected up to 100 min of exposure. All
      parasites showed significantly increased cellular breakdown in non-susceptible
      host serum compared to the respective substrates from susceptible host fish.
      Except for M. cerebralis, the serum of the susceptible host was considerably less
      effective over time. In this species, both the primary and the secondary cells
      were affected in much shorter times than in the other two representatives.
      Inhibition of protease activity did not affect carp serum effect on M. cerebralis
      stages. We suggest the active components to be complement or complement induced
      factors since heat inactivation and withdrawal of bivalent metal ions lowered
      serum activity significantly. The study marks the first in vitro viability
      challenge of activated myxozoan transmission stages with teleost derived immune
      factors.

PMID- 22951230
TI  - Isolation and characterization of a novel antibacterial peptide derived from
      hemoglobin alpha in the liver of Japanese eel, Anguilla japonica.
AB  - We isolated and characterized a novel antibacterial peptide, AJHbalpha, derived
      from hemoglobin alpha in the liver of Japanese eel, Anguilla japonica. It with
      concentration of 11.30 MUM exhibited stronger antibacterial activity against
      pathogenic bacterium 1 * 10(6) cell ml(-1)Edwardsiella tarda than other two
      bacteria. The extraction procedure for AJHbalpha included extraction with acetate
      acid, ultrafiltration, cation-exchange chromatography on HiTrapTM CM FF, reverse
      phase liquid chromatography on Source 5R RPC and C18 RP-HPLC. MALDI-TOF MS
      suggested that the peptide had an observed molecular weight of 2388.05 Da. Its
      amino acid sequence determined by Edman degradation was similar to those of
      hemoglobin alpha chain in other fish by BLAST analysis. A complete N-terminal
      amino acid sequence of the AJHbalpha was FAHWPDLGPGSPSVKKHGKVIM corresponding to
      the cDNA sequence by RACE amplification. Its synthetic peptide had strong
      antibacterial activities against ten Gram-positive or negative bacteria. To our
      knowledge, AJHbalpha was the first identified fragment of hemoglobin alpha chain
      with strong antibacterial activity in fish.

PMID- 22951231
TI  - The reporting of anal cytology and histology samples: establishing terminology
      and criteria.
AB  - Our understanding of the human papillomavirus (HPV) related cytomorphology and
      histopathology of the anal canal is underpinned by our knowledge of HPV infection
      in the cervix. In this review, we utilise cervical reporting of cytological and
      histological specimens as a foundation for the development of standardised and
      evidence-based terminology and criteria for reporting of anal specimens. We
      advocate use of the Australian Modified Bethesda System 2004 for reporting anal
      cytology. We propose the use of a two-tiered histological reporting system for
      noninvasive disease - low-grade and high-grade anal intraepithelial neoplasia.
      These classification systems reflect current understanding of the biology of HPV
      and enhance diagnostic reproducibility. Biomarkers such as p16(INK4A) may prove
      useful in further improving diagnostic accuracy. Standardisation is important
      because it will increase the value of the data collected as Australian centres
      develop programs for screening for anal neoplasia.

PMID- 22951232
TI  - A portrait of the GET pathway as a surprisingly complicated young man.
AB  - Many eukaryotic membrane proteins have a single C-terminal transmembrane domain
      that anchors them to a variety of organelles in secretory and endocytic pathways.
      These tail-anchored (TA) proteins are post-translationally inserted into the
      endoplasmic reticulum by molecular mechanisms that have long remained mysterious.
      This review describes how, in just the past 5 years, intense research by a
      handful of laboratories has led to identification of all the key components of
      one such mechanism, the guided entry of TA proteins (GET) pathway, which is
      conserved from yeast to man. The GET pathway is both surprisingly complicated and
      yet more experimentally tractable than most other membrane insertion mechanisms,
      and is rapidly revealing new fundamental concepts in membrane protein biogenesis.

PMID- 22951234
TI  - Does protein phosphorylation govern host cell entry and egress by the
      Apicomplexa?
AB  - Members of the phylum Apicomplexa are responsible for a wide range of diseases in
      humans and animals. The absence of an effective vaccine or safe curing drugs and
      the continuous emergence of resistant parasites to available treatments impose a
      high demand on the identification of novel targets for intervention against the
      apicomplexans. Protein kinases are considered attractive potential therapeutic
      targets not only against cancers but also to combat infectious diseases. The
      scope and aim of this review is to report on the recent progress in dissecting
      the impact of protein phosphorylation in regulating motility and invasion.

PMID- 22951233
TI  - Molecular mechanisms of host cell egress by malaria parasites.
AB  - Egress is a crucial step for malaria parasites to progress from one host cell to
      another. The rapid transition between host cells is mediated by the invasive
      merozoite stages. Merozoite egress from the enveloping cell includes the rupture
      of two membranes, the membrane of the parasitophorous vacuole and the host cell
      membrane. Egress from the host cell is also of importance for the
      intraerythrocytic gametocytes in order to undergo gametogenesis following their
      transmission to the mosquito during the blood meal. An increasing number of
      studies have aimed to identify the molecules involved in host cell egress by
      malaria parasites and decipher the sequence of membrane rupture. Recent work has
      acknowledged the crucial roles of plasmodial and host-derived proteases in
      membrane rupture and has indicated the involvement of secretory vesicles in
      priming the enveloping membranes for egress. This review highlights recent
      insight into the mechanisms of host cell egress by Plasmodium parasites. We will
      discuss the mode of egress of intrahepatic and intraerythrocytic parasites and
      their measures to evade the host immune system during this process.

PMID- 22951235
TI  - Introduction: a fresh look at monoamine oxidase inhibitors for depression.

PMID- 22951236
TI  - The epidemiology of depression and the evolution of treatment.
AB  - Depression is a prevalent and pernicious disorder. About 1 in 5 US adults have at
      least 1 lifetime episode of major depression. Of those with depression, the
      majority will relapse over the long-term and many will have poor mental health
      outcomes and psychosocial disabilities. Over the past century, a range of
      treatments, including medications with varying mechanisms of action, have been
      developed to manage depression. Treatments from seizure therapies to an array of
      medications--amphetamine, tricyclic antidepressants, monoamine oxidase
      inhibitors, mixed-action antidepressants, selective serotonin reuptake
      inhibitors, and dual reuptake inhibitors--have evolved.

PMID- 22951237
TI  - The role of monoamine oxidase inhibitors in depression treatment guidelines.
AB  - Monoamine oxidase inhibitors (MAOIs) have proven efficacy for treating depression
      and for decades have been a preferred treatment for patients with atypical
      depression, high levels of anxiety, anergic bipolar depression, and treatment
      resistant depression. However, MAOIs are infrequently used due to safety and
      tolerability concerns and the need for dietary restrictions. Current guidelines,
      which are reviewed here, recommend MAOIs as third-, fourth-, or fifth-line
      treatments due to these concerns. However, a transdermal formulation of
      selegiline limits the need for dietary restrictions and has fewer side effects
      than many more widely used antidepressants. The availability of a safer and more
      tolerable formulation gives clinicians another option in their armamentarium for
      treating depression.

PMID- 22951238
TI  - Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an
      update.
AB  - Monoamine oxidase inhibitors (MAOIs) are effective treatments for depression that
      has atypical features or that has failed to respond to other antidepressants.
      However, MAOIs are underused because clinicians are concerned about dietary and
      drug interactions with this class of medication. Hypertensive crisis and
      serotonin syndrome can occur in rare cases due to interactions between MAOIs and
      foods containing tyramine as well as interactions with serotonergic and
      sympathomimetic agents. A better understanding of the foods and drugs that can
      cause adverse reactions, as well as knowledge of newer MAOIs with mechanisms of
      action and delivery methods that reduce these risks, may help clinicians to
      consider the use of these medications, when appropriate, in their patients with
      depression.

PMID- 22951239
TI  - The transdermal delivery system of monoamine oxidase inhibitors.
AB  - Monoamine oxidase inhibitors (MAOIs) were once widely used as effective
      treatments for major depressive disorder, particularly for patients with atypical
      or treatment-resistant depression. Today, MAOIs have largely been replaced by
      newer antidepressants because of concerns over potential serious side effects due
      to their mechanism of action. Monoamine oxidase (MAO) is an enzyme that
      metabolizes serotonin, norepinephrine, and dopamine, the neurotransmitters that
      are most associated with depression; inhibiting MAO, therefore, makes more of
      these neurotransmitters available for synaptic action. However, MAO also
      metabolizes tyramine, a trace amine found in some foods that acts as a
      sympathomimetic. Allowing excess tyramine to accumulate via MAO inhibition can
      result in hypertensive crisis due to the release of norepinephrine; therefore,
      patients taking an MAOI have had to follow dietary restrictions to avoid tyramine
      rich foods. Hypertensive crisis may also be precipitated by using MAOIs in
      conjunction with other drugs that have vasoconstrictive properties, that act as
      sympathomimetics, or that inhibit the reuptake of norepinephrine. Serotonin
      syndrome is another serious adverse effect that can potentially occur when using
      an MAOI with another drug that inhibits the reuptake of serotonin. In this
      article, the mechanism of action of MAOIs is reviewed, along with that of a newer
      MAOI formulation that lessens the need for dietary restrictions and has a greater
      safety and tolerability profile than the older oral formulations.

PMID- 22951240
TI  - Issues in adherence to treatment with monoamine oxidase inhibitors and the rate
      of treatment failure.
AB  - In 2000, the economic burden of depression in the United States was estimated to
      be $83.1 billion. Although many effective treatments are available and treatment
      rates have increased, response and remission rates for patients with depression
      remain low and multiple treatment trials are often required. Whether patients are
      adherent to their medication affects response and remission rates, and
      nonadherence is common among patients with depression. Increasing adherence
      improves treatment outcomes and lowers treatment costs. Interventions that
      increase adherence include educational, behavioral, affective, and provider
      targeted strategies; transdermal delivery of drugs also may increase adherence by
      simplifying the patient's medication regimen. While monoamine oxidase inhibitors
      (MAOIs) have proven efficacy for depression, particularly for patients with
      treatment-resistant or atypical depression, they are underprescribed due, in
      part, to concerns over dietary and drug restrictions that are required to avoid
      potential serious side effects. However, newer MAOI formulations, including a
      transdermal delivery system, have improved safety and tolerability profiles and
      avoid or lessen the need for dietary restrictions, giving clinicians another
      option for treating patients who may be nonadherent or nonresponsive to their
      current antidepressant.

PMID- 22951241
TI  - The use of monoamine oxidase inhibitors in primary care.
AB  - Although primary care clinicians have developed considerable expertise in
      managing patients with major depressive disorder, and a range of treatment
      strategies is currently available, some patients still fail to reach remission.
      Two strategies have fallen out of common use: treating patients with monoamine
      oxidase inhibitors (MAOIs) and subgrouping patients by diagnosis when selecting
      antidepressant treatment. Monoamine oxidase inhibitors became less popular
      because other treatments were perceived to be safer and easier to use. However, a
      newer transdermal formulation of an MAOI that limits the need for the dietary
      restrictions of oral MAOIs may make it worthwhile to consider using this class of
      medication in patients who have failed several treatment trials. Although adverse
      events due to patients' diets are less likely with the transdermal MAOI,
      clinicians should still be alert for drug interactions and observe recommended
      washout periods. Patients who may benefit from MAOI treatment include those with
      treatment-resistant depression, atypical depression, anxiety, or anergic bipolar
      depression and those who have experienced intolerable metabolic or sexual side
      effects with other medications.

PMID- 22951242
TI  - Discussion: a fresh look at monoamine oxidase inhibitors for depression.

PMID- 22951243
TI  - Constant connections: piloting a mobile phone-based peer support program for Nuer
      (southern Sudanese) women.
AB  - Refugee women have poor psychosocial health as a result of past trauma and
      difficulties associated with settlement. This study was a pilot to find out how
      to use mobile phone-based peer support to improve the psychosocial health of, and
      facilitate settlement in a group of nine Nuer refugee women in Melbourne,
      Australia. Nine participants recruited by a community leader received peer
      support training over two five-week periods. They were further provided with
      mobile phone recharge vouchers to call one another to practice peer support
      techniques. The fifth and final sessions were focus groups to evaluate the
      intervention. Notes from the focus groups were thematically analysed. The women
      reported greater confidence and empowerment as they received more support, had
      better connections within the group and better access to information.
      Relationships with friends, family and the community became richer as they
      adopted and experienced more functional communication patterns. Using mobile
      phones for peer support helped to re-create community by bridging the
      geographical distance that separates refugee women. It allowed the women, from
      similar backgrounds and with similar experiences, to provide mutual support and
      exchange information through a verbal channel, the form of communication they are
      most comfortable with. The program demonstrates the positive psychosocial effect
      of peer support in a refugee community, and provides a viable model for using
      mobile phones in health promotion interventions. The successful outcomes, as
      perceived by the participants, are indicative of the potential of using
      technology to bridge health inequities in a marginalised group.

PMID- 22951244
TI  - Feasibility and acceptability of nurse-led youth clinics in Australian general
      practice.
AB  - Internationally, youth access to primary health care is problematic due to
      documented barriers such as cost, concerns about confidentiality, and knowledge
      about when to attend and available services. The treatment of health problems
      earlier in life together with engagement in prevention and health education can
      optimise youth health and maximise the potential of future wellbeing. This study
      investigated the feasibility, acceptability and cost of establishing nurse-led
      youth clinics in Victoria, Australia. Three general practices in rural and
      regional areas of Victoria implemented the nurse-led youth health clinics. The
      clinics were poorly attended by young people. Practice nurses identified several
      barriers to the clinic attendance including the short timeframe of the study, set
      times of the clinics and a lack of support for the clinics by some GPs and
      external youth health clinics, resulting in few referrals. The clinics cost from
      $5912 to $8557 to establish, which included training the practice nurses.
      Benefits of the clinics included increased staff knowledge about youth health
      issues and improved relationships within the general practice staff teams. The
      implementation of youth health clinics is not feasible in a short timeframe and
      to maximise use of the clinics, all members of the general practice team need to
      find the clinics acceptable. 

PMID- 22951245
TI  - Nitric oxide and obstructive sleep apnea.
AB  - Obstructive sleep apnea is a common disease, affecting 16% of the working age
      population. Although sleep apnea has a well-established connection to daytime
      sleepiness presumably mediated through repetitive sleep disruption, some other
      consequences are less well understood. Clinical, epidemiological, and
      physiological investigations have demonstrated a connection between sleep apnea
      and daytime hypertension. The elevation of arterial pressure is evident during
      waking, when patients are not hypoxic, and is mediated by sustained
      sympathoexcitation and by altered peripheral vascular reactivity. This review
      summarizes data suggesting that both the sympathoexcitation and the altered
      vascular reactivity are, at least in part, a consequence of reduced expression of
      nitric oxide synthase, in neural tissue and in endothelium. Reduced nitric oxide
      generation in central and peripheral sites of sympathoregulation and in
      endothelium together may, in part, explain the elevations in waking pressures
      observed in sleep apnea patients.

PMID- 22951246
TI  - A superovulation protocol for the spiny mouse (Acomys cahirinus).
AB  - This study aimed to develop a superovulation protocol for the spiny mouse (Acomys
      cahirinus). The spiny mouse is a desert-adapted rodent species, with a long
      oestrus cycle (11 days) compared with rat and mouse, and gives birth to few (mean
      litter size is 3) precocial offspring after a relatively long gestation (39
      days). We successfully optimised a superovulation protocol that elicited a 5-fold
      increase in the normal ovulation rate of this species. To induce superovulation
      in the spiny mouse 2 injections of equine chorionic gonadotrophin (eCG, 10 IU
      each), 9h apart, were required, followed by 20 IU of human chorionic
      gonadotrophin (hCG). This protocol was successful in 100% of females trialed and
      at 33 h post-hCG an average of 14.7 +/- 1.5, 1-2 cell embryos were recovered.
      Histological analysis of ovaries following superovulation revealed large corpus
      lutea and post-ovulatory follicles occupying a large part of the ovary. Ovulation
      commenced 6-12 h after the hCG injection and continued until 24-33 h post-hCG as
      indicated by both histological analysis of ovaries and the presence of
      oocytes/embryos in the oviduct. This superovulation protocol will facilitate the
      development of an in vitro culture system for spiny mouse embryos.

PMID- 22951247
TI  - It's just too hard! Australian health care practitioner perspectives on barriers
      to advance care planning.
AB  - This article presents findings from six focus groups with health care
      practitioners in an Australian hospital during 2010, which sought to elicit their
      perspectives on the barriers for people to plan their future health care should
      they become unwell. Such knowledge is invaluable in overcoming the barriers
      associated with advance care planning and enhancing the uptake of advance
      directives and the appointment of an enduring power of attorney for people of all
      ages. A person's rights to self-determination in health care, including decision
      making about their wishes for future care in the event they lose cognitive
      capacity, should not be overlooked against the backdrop of increasing pressure on
      health care systems. Findings suggest that multiple barriers exist, from
      practitioners' perspectives, which can be divided into three major categories,
      namely: patient-centred, practitioner-centred and system-centred barriers.
      Specifically, patient-centred barriers include lack of knowledge, accessibility
      concerns, the small 'window of opportunity' to discuss advance care planning,
      emotional reactions and avoidance when considering one's mortality, and
      demographic influences. At the practitioner level, barriers relate to a lack of
      knowledge and uncertainty around advance care planning processes. Systemically,
      legislative barriers (including a lack of a central registry and conflicting
      state legislation), procedural issues (particularly in relation to assessing
      cognitive capacity and making decisions ad hoc) and questions about delegation,
      roles and responsibilities further compound the barriers to advance care
      planning.

PMID- 22951248
TI  - Prevalence and predictors of high-grade anal intraepithelial neoplasia in a
      community-based sample of homosexual men.
AB  - BACKGROUND: We report the prevalence and predictors for high-grade anal
      intraepithelial neoplasia (HGAIN) in community-based cohorts of HIV-negative and
      HIV-positive homosexual men in Sydney, Australia. METHODS: A cross-sectional
      study of consecutive participants in both cohorts was performed in 2005 (204 HIV
      negative and 128 HIV-positive men). Anal swabs collected by a research nurse
      underwent cytological analysis, using the ThinPrep procedure, and human
      papillomavirus (HPV) testing. Participants who had cytological abnormalities
      other than low-grade squamous epithelial lesions (SIL) were referred for high
      resolution anoscopy (HRA). RESULTS: A total of 114 men had cytological
      abnormalities (24.3% of HIV-negative and 57.5% of HIV-positive men, odds ratio
      (OR)=4.21, 95% confidence interval (CI) 2.57-6.90). However, only three (2.3%)
      HIV-positive men and no HIV-negative men had high-grade SIL on anal cytology.
      Seventy-seven men were referred for HRA, of whom 63 (81.8%) attended.
      Histologically confirmed HGAIN was detected in 21 (33.3%). The prevalence of
      HGAIN was higher in HIV-positive men (10.8%) than in HIV-negative men (5.0%,
      OR=2.29, 95% CI 0.93-5.63, P=0.071). HGAIN was not related to age but was
      strongly associated with the detection of high-risk types of anal HPV (OR=10.1,
      95% CI 1.33-76.2) rather than low-risk types (OR=1.97, 95% CI 0.74-5.25).
      CONCLUSION: HGAIN was prevalent in homosexual men across all age groups and was
      more than twice as common in HIV-positive men compared with HIV-negative men. The
      presence of high-risk anal HPV was highly predictive of HGAIN.

PMID- 22951249
TI  - Early clinical characteristics according to developmental stage in children with
      definite moyamoya disease.
AB  - The objective is to clarify the early clinical characteristics in childhood
      moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic
      rates were assessed in 64 children (0-18 years) with definite MD according to
      developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5
      years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median
      ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in
      toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was
      observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6
      months before main symptoms (6/11). As an initial symptom, weakness was observed
      in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and
      unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was
      observed in 27% (17/64): frequently in infancy (100%, P<0.01), as the focal type
      (71%), and in the right extremity (3:1). Isolated seizures without other symptoms
      was frequent in children ~5 years (P<0.01). Severe headache associated with MD
      was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in
      school age, frequently during eating (28%); and in toddlerhood/preschool age,
      during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset
      were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%,
      respectively. Symptomatic progression at diagnosis was observed in 38% (24/64).
      Initial clinical characteristics in childhood definite MD differed according to
      developmental stage and from at diagnosis.

PMID- 22951251
TI  - An evaluation of the changes in distance from the external sole surface to the
      distal phalanx in heifers in their first lactation.
AB  - Thin soles are a significant cause of lameness in dairy cattle but in most cases
      the diagnosis is based on subjective assessment. Ultrasonography has been used to
      more directly estimate sole thickness, but mostly on a one-off basis or over a
      short period of time. Data over a longer period of time (such as a lactation
      period) are lacking and there are no descriptions of the normal changes that
      occur over time and to show how sole thickness at calving relates to thickness
      later in lactation. This study measured the distance between the external sole
      surface and the distal phalanx (DP) in 25 mixed breed (Jersey cross Friesian and
      Friesian) heifers on five occasions over their first lactation (approximately 10,
      60, 110, 160 and 220 days post calving). There was a significant effect of claw
      (medial/lateral) and of time after calving on DP. Mean DP was highest on day 10
      and was lowest on day 110 at the tip of the distal phalanx (S1) and on day 160 25
      mm towards the heel from the tip (S2). DP was greater at S1 in medial claws and
      S2 in lateral claws. Although mean DP decreased between days 10 and 110, this
      change was correlated to DP at day 10. At S1 claws with a DP of <7.5mm tended to
      increase in thickness between day 10 and 110. Claws which were <= 8.25 mm at day
      10 were 2.43 (95% CI 0.86-6.89) times more likely to be thin (<7.0mm) at day 110,
      but of the 12 thin claws at day 110, six had had an adequate DP (>8.25 mm) at day
      10. A single measurement of DP at calving was not an effective method for
      predicting which claws would became thin during lactation.

PMID- 22951250
TI  - A descriptive review of the peer and non-peer reviewed literature on the
      treatment and prevention of foot lameness in cattle published between 2000 and
      2011.
AB  - The aim of this study was to collate and review the peer and non-peer reviewed
      English language literature on the treatment and prevention of foot lameness in
      cattle published since January 2000. The study aimed to identify deficits in
      knowledge and areas of disparity between what is recommended in the field by
      veterinarians, foot trimmers and advisors and what has been substantiated
      experimentally. Peer reviewed literature containing original work was gathered by
      searching three databases. Papers were categorised and reviewed if they contained
      material on treatment or prevention. Non-peer reviewed clinical materials were
      collated from a range of sources. The materials were reviewed and categorised
      based on whether they recommended a range of possible treatment and prevention
      strategies. The peer reviewed data base contained 591 papers, of which 286
      contained information on treatment or prevention. The vast majority of papers
      (258) concerned prevention; only a small number covered treatment (31) and of
      these only three contained information on the treatment of sole ulcers or white
      line disease. The number of intervention studies and trials was low; most papers
      on prevention were observational. Generally, lesion specific outcomes were not
      described making the findings of these papers difficult to use clinically. The
      non-peer reviewed material contained 46 sources; they varied significantly in
      regard to the treatments they advocated with some texts directly contradicting
      each other. Some aspects of prevention recommended in these sources seemed poorly
      supported by findings from the research literature. Well designed intervention
      studies are required to address these deficits.

PMID- 22951252
TI  - Alpaca semen quality in relation to different diets.
AB  - The aim of the present study was to evaluate the biochemical composition of
      seminal plasma, along with semen quality, of alpacas maintained on different
      diets (hay; hay+pasture grazing; pasture grazing+sheep concentrate; pasture
      grazing+horse concentrate; Periods 1-4, respectively). Alpacas (n=5) were fed the
      four different diets for a period of 6 weeks each. During the period of feeding
      of each diet, semen was collected using an artificial vagina to determine its
      volume, viscosity, sperm concentration and sperm motility. Moreover, testicular
      volume and body condition score were evaluated. Seminal plasma was analysed
      biochemically to measure total protein, triglyceride, cholesterol, gamma-glutamyl
      transferase, alanine aminotransferase (ALT) and alkaline phosphatase levels.
      Protein profiles were investigated using one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. There was high variability in semen
      parameters between different males maintained on the same diet. Semen volume
      increased significantly (P<0.05) when alpacas were fed diets containing
      commercial sheep and horse concentrates. In contrast, sperm concentration and
      motility decreased significantly (P<0.05) from Period 1 to Period 4. Dietary
      changes had no effect on viscosity. Significant reductions were seen in
      triglyceride and cholesterol content, as well as gamma-glutamyl transferase, ALT
      and alkaline phosphatase concentrations, from Period 1 to Period 4. Regardless of
      experimental period, a wide variation was seen in seminal plasma enzyme
      concentrations between alpacas, whereas diet had no effect on glucose and total
      protein concentrations in the seminal plasma. Eight protein bands, with molecular
      weights ranging from 200 to 14kDa, were considered in electrophoresis gel after
      image analysis. Proteins fractions of the 14-kDa (total protein express in mddL(
      1) with a molecular weight of 14-kDa, TP8) and 21-kDa (total protein express in
      mddL(-1) with a molecular weight of 21-kDa, TP7) bands were not present in all
      samples of alpaca seminal plasma. There were no significant changes in the
      concentration of any protein fractions during the four periods. Moreover, the
      protein fraction of the 60-kDa (total protein express in mddL(-1) with a
      molecular weight of 60-kDa, TP3) band was the most prevalent in all periods.
      These results demonstrate that there are marked changes in semen quality, as well
      as some parameters related to the composition of alpaca seminal plasma, that are
      dependent on diet, which may indicate the need for specific diet formulation to
      improve reproductive performance. We hypothesise that, in alpacas, the mechanisms
      underlying the changes in some reproductive traits in response to feeding
      regimens could be related to changes in the endocrine-gonadal system.

PMID- 22951253
TI  - Telaprevir: a hepatitis C NS3/4A protease inhibitor.
AB  - BACKGROUND: Telaprevir is a hepatitis C NS3/4A protease inhibitor approved by the
      US Food and Drug Administration as part of combination therapy for the management
      of chronic hepatitis C virus (HCV) genotype 1 infection. OBJECTIVE: The article
      reviews published literature on telaprevir, including its chemistry, mechanism of
      action, resistance, pharmacodynamic and pharmacokinetic properties, drug
      interactions, therapeutic efficacy, HIV/HCV coinfection, pharmacogenomics,
      adverse events, pharmacoeconomics, and dosing and administration. METHODS:
      English-language literature was included. Searches of MEDLINE and BIOSIS
      databases from 1975 through January 2012 were performed. Emphasis was placed on
      reference citations involving clinical trials, randomized controlled trials, and
      research in humans. Additional publications were found by searching the reference
      lists of identified articles and reviewing abstracts from recent scientific
      meetings. Search terms included, but were not limited to, telaprevir, VX-950,
      hepatitis C virus genotype 1, resistance, pharmacology, pharmacokinetics,
      pharmacodynamics, drug interactions, pharmacogenomics, adverse events, and
      therapeutic use. RESULTS: Review of the databases revealed 471
      publications/abstracts on this subject. Of these, 85 were chosen based on the
      review criteria. Two Phase III studies investigated the efficacy and tolerability
      of telaprevir administered for 12 weeks (T12) when used with peginterferon alfa
      and ribavirin (PR) in treatment-naive subjects. The ADVANCE study reported that
      patients who had an extended rapid virologic response (eRVR; an undetectable HCV
      RNA level at both 4 and 12 weeks of treatment) with triple therapy could be
      treated with PR for a total of 24 weeks (T12PR24 group) versus standard PR
      treatment for 48 weeks (PR48 group [control]). The proportions of patients who
      achieved sustained virologic response (SVR; undetectable HCV RNA concentration at
      24 weeks after the completion of therapy) in the T12PR24 and PR48 groups were 89%
      and 44%, respectively. The ILLUMINATE study reported T12PR24 was noninferior to
      T12PR48 in patients with an eRVR to combination therapy. In the REALIZE study,
      patients with a history of relapse responded well to T12PR48 compared with PR48
      (SVR, 83% vs 24%). Telaprevir is a substrate/inhibitor of cytochrome P450
      (CYP3A4) and a substrate/inhibitor of P-glycoprotein and poses an important risk
      for drug interactions. Adverse drug events (ADEs) reported most commonly with
      triple therapy compared with the T or PR regimen alone were rash, pruritus,
      nausea, diarrhea, and anemia. The serious AEs most commonly reported during T +
      PR therapy were anemia, rash, and pruritus. Two reports concluded that T combined
      with PR was not cost-effective due to the high cost of telaprevir. One study
      reported that the combination of T + PR would be cost-effective if the treatment
      rate of HCV genotype 1 infected patients reached 50%. CONCLUSION: Including
      telaprevir as part of triple therapy for the management of chronic HCV genotype 1
      infection significantly increases the likelihood of achieving an SVR over
      standard dual drug therapy (PR) in both treatment-naive and -experienced
      patients. However, due to the high cost, the use of triple therapy with
      telaprevir will likely be limited to patient groups known to respond poorly to
      dual therapy.

PMID- 22951254
TI  - Anatomical investigation of a new vertical obturator nerve block technique.
AB  - BACKGROUND: We evaluated a vertical obturator nerve block (VOB) using a single
      morphological landmark and no additional distance measurement or obligatory
      changes of the needle's direction. MATERIALS AND METHOD: A total of 88 cadavers
      (176 lower limbs), prepared using Thiel's embalming method, were examined. The
      index finger was placed lateral to the palpable pubic tubercle and the needle
      inserted laterally to the distal part of the fingernail at the tubercle's level
      and advanced strictly perpendicular to the table's surface. If bone contact was
      made, the needle was slightly turned to pass the bone distally. Colored latex (5
      ml) was then injected. The injection depth was documented, then followed by
      dissection and nerve exposition. The real skin-nerve distance and the degree of
      difficulty in orientation and of palpation were measured. Additionally, the
      dissemination around the nerve or its branches and the intrapelvic spread were
      documented. RESULTS: The nerve was colored completely in 93.75%, partially in
      1.71%, and not colored in 4.54% of cases. The mean injection depth was 3.9 cm (+/
      0.7 SD) and real nerve depth was 3.8 cm (+/-0.69 SD). Bone contact necessitating
      the needle's redirection was found in 20 (11.4%) cases. Easy orientation and
      palpation of the tubercle was always found. In 40 cases, the latex spread via the
      obturator canal into the lesser pelvis. CONCLUSION: In this anatomical study, the
      VOB technique exhibits easy orientation without stimulation or ultrasound
      guidance. The nerve was located at a constant depth. The injection offered a high
      percentage of colored nerves.

PMID- 22951255
TI  - A sulfoximine-based inhibitor of human asparagine synthetase kills L-asparaginase
      resistant leukemia cells.
AB  - An adenylated sulfoximine transition-state analogue 1, which inhibits human
      asparagine synthetase (hASNS) with nanomolar potency, has been reported to
      suppress the proliferation of an l-asparagine amidohydrolase (ASNase)-resistant
      MOLT-4 leukemia cell line (MOLT-4R) when l-asparagine is depleted in the medium.
      We now report the synthesis and biological activity of two new sulfoximine
      analogues of 1 that have been studied as part of systematic efforts to identify
      compounds with improved cell permeability and/or metabolic stability. One of
      these new analogues, an amino sulfoximine 5 having no net charge at cellular pH,
      is a better hASNS inhibitor (K(I)(*)=8 nM) than 1 and suppresses proliferation of
      MOLT-4R cells at 10-fold lower concentration (IC(50)=0.1mM). More importantly,
      and in contrast to the lead compound 1, the presence of sulfoximine 5 at
      concentrations above 0.25 mM causes the death of MOLT-4R cells even when ASNase
      is absent in the culture medium. The amino sulfoximine 5 exhibits different dose
      response behavior when incubated with an ASNase-sensitive MOLT-4 cell line (MOLT
      4S), supporting the hypothesis that sulfoximine 5 exerts its effect by inhibiting
      hASNS in the cell. Our work provides further evidence for the idea that hASNS
      represents a chemotherapeutic target for the treatment of leukemia, and perhaps
      other cancers, including those of the prostate.

PMID- 22951256
TI  - Regulation of transforming growth factor beta1-dependent aldose reductase
      expression by the Nrf2 signal pathway in human mesangial cells.
AB  - Aldose reductase (AR) is a key enzyme in the alternative glucose metabolism
      pathway, the polyol pathway. To date, AR is known to be involved in several
      secondary complications of diabetes and various kidney diseases. The goal of this
      study was to elucidate how the Nrf2-anti-oxidant response element (ARE) signal
      pathway plays a role in TGFbeta1's regulation of AR expression in human renal
      mesangial cells (HRMCs). As an in vitro model system, HRMCs were used to
      investigate AR mRNA by qPCR, protein by Western blot and enzymatic activity by
      spectrophotometric assay. The ability of TGFbeta1 to induce reactive oxygen
      species (ROS) in cells was measured by electron-spin resonance (ESR) trapping
      method. Reporter assays were used to test the activity of the AR promoter region,
      and ChIP was employed to test the direct binding of Nrf2 with the endogenous AR
      promoter. Treatment of HRMCs with TGFbeta1 up-regulated the expression of AR
      mRNA, protein, and activity level. Additionally, TGFbeta1 rapidly increased
      cellular ROS levels, which in turn activated the Nrf2-ARE pathway. Either
      inhibition of ROS production or knockdown of Nrf2 in HRMCs decreased the TGFbeta1
      induction of AR expression. Nrf2 regulated AR luciferase activity specifically
      via two AREs within the AR promoter, and bound directly to the endogenous AR
      promoter. Furthermore, the TGFbeta1-mediated expression of AR required Nrf2 and
      was significantly abrogated in Nrf2-/- cells. These data show the regulation of
      AR by TGFbeta1 is induced by TGFbeta1 stimulation of ROS, which activates the
      Nrf2-ARE pathway allowing Nrf2 to directly increase AR expression in HRMCs.

PMID- 22951257
TI  - Bayesian hierarchical multi-subject multiscale analysis of functional MRI data.
AB  - We develop a methodology for Bayesian hierarchical multi-subject multiscale
      analysis of functional Magnetic Resonance Imaging (fMRI) data. We begin by
      modeling the brain images temporally with a standard general linear model. After
      that, we transform the resulting estimated standardized regression coefficient
      maps through a discrete wavelet transformation to obtain a sparse representation
      in the wavelet space. Subsequently, we assign to the wavelet coefficients a prior
      that is a mixture of a point mass at zero and a Gaussian white noise. In this
      mixture prior for the wavelet coefficients, the mixture probabilities are related
      to the pattern of brain activity across different resolutions. To incorporate
      this information, we assume that the mixture probabilities for wavelet
      coefficients at the same location and level are common across subjects.
      Furthermore, we assign for the mixture probabilities a prior that depends on a
      few hyperparameters. We develop an empirical Bayes methodology to estimate the
      hyperparameters and, as these hyperparameters are shared by all subjects, we
      obtain precise estimated values. Then we carry out inference in the wavelet space
      and obtain smoothed images of the regression coefficients by applying the inverse
      wavelet transform to the posterior means of the wavelet coefficients. An
      application to computer simulated synthetic data has shown that, when compared to
      single-subject analysis, our multi-subject methodology performs better in terms
      of mean squared error. Finally, we illustrate the utility and flexibility of our
      multi-subject methodology with an application to an event-related fMRI dataset
      generated by Postle (2005) through a multi-subject fMRI study of working memory
      related brain activation.

PMID- 22951258
TI  - A 10-year longitudinal fMRI study of narrative comprehension in children and
      adolescents.
AB  - Comprehension of spoken narratives requires coordination of multiple language
      skills. As such, for normal children narrative skills develop well into the
      school years and, during this period, are particularly vulnerable in the face of
      brain injury or developmental disorder. For these reasons, we sought to determine
      the developmental trajectory of narrative processing using longitudinal fMRI
      scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6,
      or 7, were examined annually for up to 10 years. At each fMRI session, children
      were presented with a set of five, 30s-long, stories containing 9, 10, or 11
      sentences designed to be understood by a 5 year old child. fMRI data analysis was
      conducted based on a hierarchical linear model (HLM) that was modified to
      investigate developmental changes while accounting for missing data and
      controlling for factors such as age, linguistic performance and IQ. Performance
      testing conducted after each scan indicated well above the chance (p<0.002)
      comprehension performance. There was a linear increase with increasing age in
      bilateral superior temporal cortical activation (BAs 21 and 22) linked to
      narrative processing. Conversely, age-related decreases in cortical activation
      were observed in bilateral occipital regions, cingulate and cuneus, possibly
      reflecting changes in the default mode networks. The dynamic changes observed in
      this longitudinal fMRI study support the increasing role of bilateral BAs 21 and
      22 in narrative comprehension, involving non-domain-specific integration in order
      to achieve final story interpretation. The presence of a continued linear
      development of this area throughout childhood and teenage years with no apparent
      plateau, indicates that full maturation of narrative processing skills has not
      yet occurred and that it may be delayed to early adulthood.

PMID- 22951259
TI  - Abnormal network topographies and changes in global activity: absence of a causal
      relationship.
AB  - Changes in regional brain activity can be observed following global normalization
      procedures to reduce variability in the data. In particular, spurious regional
      differences may appear when scans from patients with low global activity are
      compared to those from healthy subjects. It has thus been suggested that the
      consistent increases in subcortical activity that characterize the abnormal
      Parkinson's disease-related metabolic covariance pattern (PDRP) are artifacts of
      global normalization, and that similar topographies can be identified in scans
      from healthy subjects with varying global activity. To address this issue, we
      examined the effects of experimental reductions in global metabolic activity on
      PDRP expression. Ten healthy subjects underwent 18F-fluorodeoxyglucose PET in
      wakefulness and following sleep induction. In all subjects, the global metabolic
      rate (GMR) declined with sleep (mean -34%, range: -17 to -56%), exceeding the
      test-retest differences of the measure (p<0.001). By contrast, sleep-wake
      differences in PDRP expression did not differ from test-retest differences, and
      did not correlate (R2=0.04) with concurrent declines in global metabolic
      activity. Indeed, despite significant GMR reductions in sleep, PDRP values
      remained within the normal range. Likewise, voxel weights on the principal
      component patterns resulting from combined analysis of the sleep and wake scans
      did not correlate (R2<0.07) with the corresponding regional loadings on the PDRP
      topography. In aggregate, the data demonstrate that abnormal PDRP expression is
      not induced by reductions in global activity. Moreover, significant declines in
      GMR are not associated with the appearance of PDRP-like spatial topographies.

PMID- 22951260
TI  - Alterations in grooming activity and syntax in heterozygous SERT and BDNF
      knockout mice: the utility of behavior-recognition tools to characterize mutant
      mouse phenotypes.
AB  - Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key
      modulators of molecular signaling, cognition and behavior. Although SERT and BDNF
      mutant mouse phenotypes have been extensively characterized, little is known
      about their self-grooming behavior. Grooming represents an important behavioral
      domain sensitive to environmental stimuli and is increasingly used as a model for
      repetitive behavioral syndromes, such as autism and attention
      deficit/hyperactivity disorder. The present study used heterozygous ((+/-)) SERT
      and BDNF male mutant mice on a C57BL/6J background and assessed their spontaneous
      self-grooming behavior applying both manual and automated techniques. Overall,
      SERT(+/-) mice displayed a general increase in grooming behavior, as indicated by
      more grooming bouts and more transitions between specific grooming stages.
      SERT(+/-) mice also aborted more grooming bouts, but showed generally unaltered
      activity levels in the observation chamber. In contrast, BDNF(+/-) mice displayed
      a global reduction in grooming activity, with fewer bouts and transitions between
      specific grooming stages, altered grooming syntax, as well as hypolocomotion and
      increased turning behavior. Finally, grooming data collected by manual and
      automated methods (HomeCageScan) significantly correlated in our experiments,
      confirming the utility of automated high-throughput quantification of grooming
      behaviors in various genetic mouse models with increased or decreased grooming
      phenotypes. Taken together, these findings indicate that mouse self-grooming
      behavior is a reliable behavioral biomarker of genetic deficits in SERT and BDNF
      pathways, and can be reliably measured using automated behavior-recognition
      technology.

PMID- 22951261
TI  - Experimental procedures to mitigate electron beam induced artifacts during in
      situ fluid imaging of nanomaterials.
AB  - Scanning transmission electron microscopy of various fluid and hydrated
      nanomaterial samples has revealed multiple imaging artifacts and electron beam
      fluid interactions. These phenomena include growth of crystals on the fluid stage
      windows, repulsion of particles from the irradiated area, bubble formation, and
      the loss of atomic information during prolonged imaging of individual
      nanoparticles. Here we provide a comprehensive review of these fluid stage
      artifacts, and we present new experimental evidence that sheds light on their
      origins in terms of experimental apparatus issues and indirect electron beam
      sample interactions with the fluid layer. A key finding is that many artifacts
      are a result of indirect electron beam interactions, such as production of
      reactive radicals in the water by radiolysis, and the associated crystal growth.
      The results presented here will provide a methodology for minimizing fluid stage
      imaging artifacts and acquiring quantitative in situ observations of nanomaterial
      behavior in a liquid environment.

PMID- 22951262
TI  - Advanced reconstruction algorithms for electron tomography: from comparison to
      combination.
AB  - In this work, the simultaneous iterative reconstruction technique (SIRT), the
      total variation minimization (TVM) reconstruction technique and the discrete
      algebraic reconstruction technique (DART) for electron tomography are compared
      and the advantages and disadvantages are discussed. Furthermore, we describe how
      the result of a three dimensional (3D) reconstruction based on TVM can provide
      objective information that is needed as the input for a DART reconstruction. This
      approach results in a tomographic reconstruction of which the segmentation is
      carried out in an objective manner.

PMID- 22951263
TI  - Effect of an ultrafast laser induced plasma on a relativistic electron beam to
      determine temporal overlap in pump-probe experiments.
AB  - In this paper we report on a simple and robust method to measure the absolute
      temporal overlap of the laser and the electron beam at the sample based on the
      effect of a laser induced plasma on the electron beam transverse distribution,
      successfully extending a similar method from keV to MeV electron beams. By
      pumping a standard copper TEM grid to form the plasma, we gain timing information
      independent of the sample under study. In experiments discussed here the optical
      delay to achieve temporal overlap between the pump electron beam and probe laser
      can be determined with ~1 ps precision.

PMID- 22951264
TI  - Study of atomic structure and electronic structure of an AA'3B4O12 double
      perovskite CaCu3Ir4O12 using STEM imaging and EELS techniques.
AB  - A newly discovered 1:3 A-site-ordered AA'3B4O12 perovskite oxide CaCu3Ir4O12
      which has unusual electrical and magnetic properties was investigated using STEM
      imaging and EELS techniques in a probe corrected microscope. The target sample
      was compared with the other two iso-structural oxides of CaCu3Ru4O12 and
      CaCu3Ti4O12 with dissimilar physical properties. It has been found by STEM HAADF
      imaging that Ca and Cu on A and A' sites are ordered as expected. Oxygen atoms
      are imaged with STEM ABF imaging. The fine structures of the Cu L2,3 core loss
      and O-K edges show that the electronic structure of CaCu3Ir4O12 is very close to
      that of CaCu3Ru4O12, but different from CaCu3Ti4O12. The O-K near edge fine
      structures show extensive hybridization of Ir 5d and O 2p band. Cu L2,3 peaks
      indicate Cu in CaCu3Ir4O12 has 2+ valence, though Cu(2+) electrons mainly
      localized, they might have strong interactions with Ir(4+) 5d electrons through
      Ir-O-Cu, similar to the strong coupling of Ru with Cu in CaCu3Ru4O12.

PMID- 22951265
TI  - Microstructural changes in silicon induced by patterning with focused ion beams
      of Ga, Si and Au.
AB  - We use focused beams of Ga(+), Au(+) and Si(++) ions to induce local
      microstructural changes in single crystal silicon. The ions were delivered as
      single spot pulses into thin Si membranes that could subsequently be imaged and
      annealed in situ in a transmission electron microscope. For each ion, the focused
      ion beam implantation created an array of amorphous regions in the crystalline
      membrane. Annealing causes solid phase epitaxial regrowth to take place, but we
      show that the resulting microstructure depends on the ion species. For Ga(+) and
      Au(+), precipitates remain after recrystallization, while for Si(++), dislocation
      loops form around the periphery of each implanted spot. We attribute these loops
      to defects formed during solid phase epitaxial regrowth, with controlled
      placement of the loops possible.

PMID- 22951266
TI  - Skeletal adaptations associated with pre-pubertal gymnastics participation as
      determined by DXA and pQCT: a systematic review and meta-analysis.
AB  - Participation in gymnastics prior to puberty offers an intriguing and unique
      model, particularly in girls. The individuality comes from both upper and lower
      limbs being exposed to high mechanical loading through year long intensive
      training programs, initiated at a young age. Studying this unique model and the
      associated changes in musculoskeletal health during growth is an area of specific
      interest. Previous reviews on gymnastics participation and bone health have been
      broad; and not limited to a particular maturation period, such as pre-puberty.
      OBJECTIVES: To determine the difference in skeletal health between pre-pubertal
      girls participating in gymnastics compared with non-gymnasts. DESIGN: Meta
      analysis. METHODS: Following a systematic search, 17 studies were included in
      this meta-analysis. All studies used dual-energy X-ray absorptiometry to assess
      bone mineral density and bone mineral content. In addition, two studies included
      peripheral quantitative computed tomography. RESULTS: Following the
      implementation of a random effects model, gymnasts were found to have greater
      bone properties than non-gymnasts. The largest difference in bone health between
      gymnasts and non-gymnasts was observed in peripheral quantitative computed
      tomography-derived volumetric bone mineral density at the distal radius (d=1.06).
      CONCLUSIONS: Participation in gymnastics during pre-pubertal growth was
      associated with skeletal health benefits, particularly to the upper body.

PMID- 22951267
TI  - Musculoskeletal symptoms and associated risk factors among office workers with
      high workload computer use.
AB  - OBJECTIVE: Although the prevalence of reported discomfort by computer workers is
      high, the impact of high computer workload on musculoskeletal symptoms remains
      unclear. The purpose of this study was to investigate the prevalence of
      musculoskeletal symptoms for office workers with high computer workload. The
      association between risk factors and musculoskeletal symptoms was also assessed.
      METHODS: Two questionnaires were posted on the Web sites of 3 companies and 1
      university to recruit computer users in Tainan, Taiwan, during May to July 2009.
      The 12-item Chinese Health Questionnaire and Musculoskeletal Symptom
      Questionnaire were chosen as the evaluation tools for musculoskeletal symptoms
      and its associated risk factors. Chinese Health Questionnaire greater than 5 and
      computer usage greater than 7 h/d were used to as the cutoff line to divide
      groups. Descriptive statistics were computed for mean values and frequencies.
      chi(2) Analysis was used to determine significant differences between groups. A
      0.05 level of significance of was used for statistical comparisons. RESULTS: A
      total of 254 subjects returned the questionnaire, of which 203 met the inclusion
      criteria. The 3 leading regions of musculoskeletal symptoms among the computer
      users were the shoulder (73%), neck (71%), and upper back (60%) areas. Similarly,
      the 3 leading regions of musculoskeletal symptoms among the computer users with
      high workload were shoulder (77.3%), neck (75.6%), and upper back (63.9%)
      regions. High psychologic distress was significantly associated with shoulder and
      upper back complaints (odds ratio [OR], 3.46; OR, 2.24), whereas a high workload
      was significantly associated with lower back complaints (OR, 1.89). Females were
      more likely to report shoulder complaints (OR, 2.25). CONCLUSIONS: This study
      found that high psychologic distress was significantly associated with shoulder
      and upper back pain, whereas high workload was associated with lower back pain.
      Women tended to have a greater risk of shoulder complaints than men. Developing
      an intervention that addresses both physical and psychologic problems is
      important for future studies.

PMID- 22951268
TI  - A Literature Review of Pediatric Spinal Manipulation and Chiropractic
      Manipulative Therapy: Evaluation of Consistent Use of Safety Terminology.
AB  - OBJECTIVE: The purpose of this study was to perform a literature search to
      identify relevant studies on pediatric spinal manipulation and chiropractic
      manipulative therapy and to assess if safety terminology was consistent with the
      International Conference on Harmonisation of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH). METHODS: A literature search
      was performed in PubMed using the following terms: spinal manipulation pediatric,
      chiropractic safety pediatric, and manual therapy safety pediatric. PubMed was
      searched from inception to April 2012 with no language limitations. The
      international standards included the terminology of the World Health Organization
      on side effects, adverse reactions, adverse events and the ICH guideline
      templates that were adapted for manual therapy for this study. RESULTS: Of the 9
      relevant articles identified in this study, 3 reported methodology for
      classifying safety incidents, and all 9 used safety terminology (adverse effects
      or adverse events). However, terminology was not used consistently. CONCLUSION:
      Most of the articles identified in this literature review did not use terminology
      consistent with the standards established by the ICH when reporting on safety
      incidents following pediatric spinal manipulation or chiropractic manipulative
      therapy. More efforts should be taken to include consistent terminology for
      studies of spinal manipulation and chiropractic manipulative therapy for
      children.

PMID- 22951269
TI  - Chiropractic use, health care expenditures, and health outcomes for rural and
      nonrural individuals with arthritis.
AB  - OBJECTIVE: Arthritis is considered the leading cause of disability among adults
      in the United States today and contributes substantially to the rising cost of
      health care. Residents of rural areas are especially affected. The purposes of
      this article are to describe chiropractic use by rural and nonrural individuals
      with arthritis and to identify differences in other health care use and health
      status by those using chiropractic care plus conventional care or conventional
      care alone. METHODS: A longitudinal cohort from panel 12 (N = 12440) of the
      Medical Expenditure Panel Survey spanning 2007 to 2008 was selected for this
      study to represent changes in health care expenditures and use and outcomes
      throughout this period. The population was stratified by self-reported physician
      diagnosed arthritis and rural status and compared across demographics, health
      status, and health care use and expenditures, including use of chiropractic
      services plus conventional care or conventional care alone. RESULTS: Twice as
      many rural people with arthritis had 1 or more visits with a doctor of
      chiropractic compared with nonrural persons with arthritis. More rural
      chiropractic users with arthritis reported their perceived health status as
      excellent, very good, or good compared with nonrural chiropractic users with
      arthritis and to rural people with arthritis who reported no chiropractic visits.
      Health care expenditures for other physician services were higher among rural
      chiropractic users with arthritis than nonrural users with arthritis.
      CONCLUSIONS: Differences in chiropractic use were observed between rural and
      nonrural individuals with arthritis. More studies are needed to investigate these
      differences and the impact on health care use and expenditures and outcomes of
      individuals with arthritis.

PMID- 22951270
TI  - Embryonic development of the fossorial gymnophthalmid lizards Nothobachia
      ablephara and Calyptommatus sinebrachiatus.
AB  - The evolutionary history of the lizard family Gymnophthalmidae is characterized
      by several independent events of morphological modifications to a snake-like body
      plan, such as limb reduction, body elongation, loss of external ear openings, and
      modifications in skull bones, as adaptive responses to a burrowing and fossorial
      lifestyle. The origins of such morphological modifications from an ancestral
      lizard-like condition can be traced back to evolutionary changes in the
      developmental processes that coordinate the building of the organism. Thus, the
      characterization of the embryonic development of gymnophthalmid lizards is an
      essential step because it lays the foundation for future studies aiming to
      understand the exact nature of these changes and the developmental mechanisms
      that could have been responsible for the evolution of a serpentiform (snake-like)
      from a lacertiform (lizard-like) body form. Here we describe the post
      ovipositional embryonic development of the fossorial species Nothobachia
      ablephara and Calyptommatus sinebrachiatus, presenting a detailed staging system
      for each one, with special focus on the development of the reduced limbs, and
      comparing their development to that of other lizard species. The data provided by
      the staging series are essential for future experimental studies addressing the
      genetic basis of the evolutionary and developmental variation of the
      Gymnophthalmidae.

PMID- 22951271
TI  - Skeletal development in the fossorial gymnophthalmids Calyptommatus
      sinebrachiatus and Nothobachia ablephara.
AB  - The development of the cartilaginous and bony elements that form the skull and
      axial and appendicular skeleton is described in detail for the post-ovipositional
      embryonic development of the fossorial gymnophthalmid species Calyptommatus
      sinebrachiatus and Nothobachia ablephara. Both species have a snake-like
      morphology, showing an elongated body and reduced or absent limbs, as well as
      modifications in skull bones for burrowing, such as complex articulation surfaces
      and development of bony extensions that enclose and protect the brain. Similar
      morphological changes have originated independently in several squamate groups,
      including the one that led to the snake radiation. This study characterizes the
      patterns of chondrogenesis and osteogenesis, with special emphasis on the
      features associated with the burrowing habit, and may be used for future
      comparative analyses of the developmental patterns involved in the origin of the
      convergent serpentiform morphologies.

PMID- 22951272
TI  - Migration of multipotent interstitial stem cells in Hydra.
AB  - Stem cells in Hydra represent one of the phylogenetically most ancient stem cell
      systems and, therefore, provide information for reconstructing the early history
      of stem cell control mechanisms. Hydra's interstitial stem cells are multipotent
      and differentiate into both somatic cell types and germ line cells. Although it
      is well accepted that cells of the interstitial cell lineage are migratory, the
      in vivo migratory potential of multipotent interstitial stem cells has never been
      explored. Combining in vivo tracing of genetically labeled interstitial stem
      cells and tissue transplantation, we show that in contrast to precursor cells,
      multipotent interstitial stem cells are stationary. Only when exposed to tissue
      depleted of the interstitial cell lineage, interstitial stem cells start to
      migrate and to repopulate emptied stem cell niches. We conclude that multipotent
      interstitial stem cells in Hydra are static and that microenvironmental cues
      including signals derived from the interstitial cell lineage or from niche cells
      can trigger a shift in collective stem cell behavior to start migration.

PMID- 22951273
TI  - Stomach fullness modulates prey size choice in the frillfin goby, Bathygobius
      soporator.
AB  - Behaviours related to foraging and feeding in predator-prey systems are
      fundamental to our understanding of food webs. From the perspective of a
      predator, the selection of prey size depends upon a number of factors including
      prey vulnerability, prey size, and the predator's motivation to eat. Thus,
      feeding motivation and prey visual cues are supposed to influence predator
      decisions and it is predicted that prey selection by visual cues is modulated by
      the predator's stomach fullness prior to attacking a prey. This study was
      conducted using an animal model from the rocky shores ecosystem, a predatory
      fish, the frillfin goby Bathygobius soporator, and a benthic prey, the mottled
      shore crab Pachygrapsus transversus. Our results demonstrate that frillfin gobies
      are capable of visually evaluating prey size and that the size evaluation process
      is modulated by the level of stomach fullness. Predators with an empty stomach
      (0% fullness) attacked prey that was larger than the predicted optimal size.
      Partially satiated predators (50% stomach fullness) selected prey close to the
      optimal size, while fully satiated predators (100% stomach fullness) showed no
      preference for size. This finding indicates an integrative response of the
      predator that depends on the input of both internal and external sensory
      information when choosing prey. Predator perceptions of visual cues (prey size)
      and stomach fullness modulate foraging decisions. As a result, a flexible feeding
      behaviour emerges, evidencing a clearly adaptive response in line with optimal
      foraging theory predictions.

PMID- 22951274
TI  - Central mechanisms of menthol-induced analgesia.
AB  - Menthol is one of the most commonly used chemicals in our daily life, not only
      because of its fresh flavor and cooling feeling but also because of its medical
      benefit. Previous studies have suggested that menthol produces analgesic action
      in acute and neuropathic pain through peripheral mechanisms. However, the central
      actions and mechanisms of menthol remain unclear. Here, we report that menthol
      has direct effects on the spinal cord. Menthol decreased both ipsilateral and
      contralateral pain hypersensitivity induced by complete Freund's adjuvant in a
      dose-dependent manner. Menthol also reduced both first and second phases of
      formalin-induced spontaneous nocifensive behavior. We then identified the
      potential central mechanisms underlying the analgesic effect of menthol. In
      cultured dorsal horn neurons, menthol induced inward and outward currents in a
      dose-dependent manner. The menthol-activated current was mediated by Cl(-) and
      blocked by bicuculline, suggesting that menthol activates gamma-aminobutyric acid
      type A receptors. In addition, menthol blocked voltage-gated sodium channels and
      voltage-gated calcium channels in a voltage-, state-, and use-dependent manner.
      Furthermore, menthol reduced repetitive firing and action potential amplitude,
      decreased neuronal excitability, and blocked spontaneous synaptic transmission of
      cultured superficial dorsal horn neurons. Liquid chromatography/tandem mass
      spectrometry analysis of brain menthol levels indicated that menthol was rapidly
      concentrated in the brain when administered systemically. Our results indicate
      that menthol produces its central analgesic action on inflammatory pain probably
      via the blockage of voltage-gated Na(+) and Ca(2+) channels. These data provide
      molecular and cellular mechanisms by which menthol decreases neuronal
      excitability, therefore contributing to menthol-induced central analgesia.

PMID- 22951275
TI  - Spermatogenesis is seasonal in the large hairy armadillo, Chaetophractus villosus
      (Dasypodidae, Xenarthra, Mammalia).
AB  - Very little is known about the distinct reproductive biology of armadillos. Very
      few studies have investigated armadillo spermatogenesis, with data available only
      for Euphractus sexcinctus and Dasypus novemcinctus. In the present study, we
      analysed male germ cell differentiation in the large hairy armadillo
      Chaetophractus villosus throughout the year, describing a cycle of the
      seminiferous epithelium made of eight different stages. Evaluation of the
      testis/body mass ratio, analysis of the architecture of the seminiferous
      epithelium and the frequency of defective seminiferous tubules allowed
      identification of a temporal interruption of spermatogenesis during the period
      between mid-May to July (mid-end autumn) in correlation with very low
      testosterone levels. Overall, these results suggest that spermatogenesis is
      seasonal in C. villosus.

PMID- 22951276
TI  - Non-invasive brain stimulation in the functional evaluation of alcohol effects
      and in the treatment of alcohol craving: a review.
AB  - Acute and chronic consumption of alcohol have direct effects on central nervous
      system by altering predominantly gamma-aminobutyric acidergic and glutamatergic
      neurotransmission. Abnormalities in these neurotransmitter systems can be
      demonstrated by changes in cortical excitability parameters assessed with
      transcranial magnetic stimulation (TMS). Furthermore, integrated approaches
      utilizing TMS combined with electroencephalography (EEG) enable the evaluation of
      the focal effects of alcohol on the human cortex, providing useful information,
      different from that obtained using other functional brain imaging modalities.
      Alcohol was found to modulate EEG responses evoked by motor-cortex TMS,
      predominantly at the right prefrontal cortex, indicating that ethanol alters the
      functional connectivity between motor and prefrontal areas. Alcohol decreases
      amplitudes of EEG responses of anterior parts of the cortex after left prefrontal
      TMS, suggesting a decrease of prefrontal cortical excitability. High-frequency
      repetitive TMS (rTMS) revealed significant changes in short-term plasticity of
      the primary motor cortex after acute ethanol intake and in patients with chronic
      alcohol abuse. TMS findings also support the recently emerged theory that
      abnormal function of glutamate receptors plays a relevant role in the development
      of alcohol dependence and manifestation of the alcohol withdrawal syndrome.
      Finally, initial studies provide evidence that non-invasive brain stimulation
      techniques (rTMS and transcranial direct current stimulation) might represent a
      potential therapeutic tool to reduce alcohol craving. Future studies with larger
      sample size evaluating the clinical effects of these neuromodulatory approaches
      are required to confirm and extend the preliminary findings.

PMID- 22951277
TI  - Repetitive loading damages healing ligaments more than sustained loading
      demonstrated by reduction in modulus and residual strength.
AB  - Healing ligaments have decreased strength compared to normal ligaments, leaving
      healing ligaments vulnerable to damage accumulation during normal daily
      activities at functional stresses. Rabbit medial collateral ligament gap scars
      after 14 weeks of healing were exposed to long-term creep and fatigue loading
      over a range of functional stresses. In addition to the 58 healing ligaments that
      underwent in vitro creep and fatigue testing, seven healing ligaments underwent
      only monotonic failure tests for comparison with residual strength tests that
      followed creep and fatigue testing. When exposed to repetitive loading during
      fatigue testing, healing ligaments exhibited modulus reduction earlier than when
      exposed to sustained loading during creep testing that was occasionally
      interrupted with unloading/reloading cycles to measure modulus. In other words,
      after the same loading duration, repetitive loading was more damaging than
      sustained loading. At modulus reduction, the increase in strain during fatigue
      was greater than or similar to that during creep. Healing ligaments that were
      damaged during long-term loading exhibited decreased strength and increased toe
      region strain during subsequent residual strength tests. Normal daily activities
      that result in repetitive loading of a ligament healing from an injury will
      likely cause damage to accumulate faster than activities that result in sustained
      loading.

PMID- 22951278
TI  - A paradigm for the development and evaluation of novel implant topologies for
      bone fixation: in vivo evaluation.
AB  - While contemporary prosthetic devices restore some function to individuals who
      have lost a limb, there are efforts to develop bio-integrated prostheses to
      improve functionality. A critical step in advancing this technology will be to
      securely attach the device to remnant bone. To investigate mechanisms for
      establishing robust implant fixation in bone while undergoing loading, we
      previously used a topology optimization scheme to develop optimized orthopedic
      implants and then fabricated selected designs from titanium (Ti)-alloy with
      selective laser sintering (SLS) technology. In the present study, we examined how
      implant architecture and mechanical stimulation influence osseointegration within
      an in vivo environment. To do this, we evaluated three implant designs (two
      optimized and one non-optimized) using a unique in vivo model that applied
      cyclic, tension/compression loads to the implants. Eighteen (six per implant
      design) adult male canines had implants surgically placed in their proximal,
      tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load
      of +/-22 N for 1000 cycles) was applied to one of each animal's bilateral
      implants for the latter six weeks. Following harvest, osseointegration was
      assessed by non-destructive mechanical testing, micro-computed tomography
      (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that
      implant loading enhanced osseointegration by significantly increasing construct
      stiffness, peri-implant trabecular morphology, and percentages of interface
      connectivity and bone ingrowth. While this experiment did not demonstrate a clear
      advantage associated with the optimized implant designs, osseointegration was
      found to be significantly influenced by aspects of implant architecture.

PMID- 22951279
TI  - Proteasome inhibition in cancer is associated with enhanced tumor targeting by
      the adeno-associated virus/phage.
AB  - Bacteriophage (phage), which are viruses that infect bacteria only, have shown
      promise as vehicles for targeted cancer gene therapy, albeit with poor
      efficiency. Recently, we generated an improved version of phage vectors by
      incorporating cis genetic elements of adeno-associated virus (AAV). This novel
      AAV/phage hybrid (AAVP) efficiently delivered systemically administered
      therapeutic genes to various tumor targets by displaying an integrin tumor
      targeting ligand on the phage capsid. However, inherent limitations in
      bacteriophage mean that these AAVP vectors still need to be improved. One of the
      limitations of AAVP in mammalian cells may be its susceptibility to proteasomal
      degradation. The proteasome is upregulated in cancer and it is known that it
      constitutes a barrier to gene delivery by certain eukaryotic viruses. We report
      here that inhibition of proteasome improved targeted reporter gene delivery by
      AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector
      administration to tumor-bearing mice. We also show enhanced targeted tumor cell
      killing by AAVP upon proteasome inhibition. The AAVP particles persisted
      significantly in cancer cells in vitro and in tumors in vivo after systemic
      administration, and accumulated polyubiquitinated coat proteins. Our results
      suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and
      indicate that a combination of proteasome-inhibiting drugs and AAVP should be
      considered for clinical anticancer therapy.

PMID- 22951280
TI  - Possible involvement of SDF-1/CXCL12 in the pathogenesis of Degos disease.
AB  - BACKGROUND: Degos disease or malignant atrophic papulosis is a rare occlusive
      vasculopathic disease characterized by pathognomonic cutaneous lesions and
      frequently fatal systemic involvement. The etiology of malignant atrophic
      papulosis remains unclear, and there is currently no effective treatment for
      malignant atrophic papulosis. Several chemokines can potentiate and expand the
      platelet response to increase thrombus formation. Among these chemokines, this
      study examined the expression of stromal cell-derived factor (SDF)-1/CXCL12,
      which is secreted by bone-marrow stromal and endothelial cells, activates
      megakaryocyte precursors, and costimulates platelet activation. OBJECTIVE: We
      sought to investigate and compare the expression of SDF-1/CXCL12 in tissue
      sections taken from 2 patients with Degos disease, 2 patients with other vaso
      occlusive diseases, and 2 healthy control subjects. METHODS: Immunohistochemical
      staining involving antibodies to SDF-1/CXCL12 was performed on 3 skin biopsy
      specimens taken from 2 patients with Degos disease, 1 from a patient with
      antiphospholipid syndrome, 1 from a patient with cryoglobulinemia, and 2 from
      healthy control subjects. RESULTS: Strong SDF-1/CXCL12 staining was observed in
      the infiltrating inflammatory cells in the perivascular, intravascular, and
      perineural areas in tissue samples from patients with Degos disease. No staining
      was observed in samples from patients with antiphospholipid syndrome or
      cryoglobulinemia or from healthy control subjects. LIMITATIONS: The number of
      cases available for evaluation was small. The findings were based primarily on
      the immunohistochemical results and were not confirmed using other techniques.
      CONCLUSIONS: The intense staining of SDF-1/CXCL12 in lesions attributed to Degos
      disease, demonstrated for the first time to our knowledge in this study, suggests
      SDF-1/CXCL12 involvement in the pathogenesis of the disease.

PMID- 22951281
TI  - The Teamwork Study: enhancing the role of non-GP staff in chronic disease
      management in general practice.
AB  - There is evidence for a team-based approach in the management of chronic disease
      in primary health care. However, the standard of care is variable, probably
      reflecting the limited organisational capacity of health services to provide the
      necessary structured and organised care for this group of patients. This study
      aimed to evaluate the impact of a structured intervention involving non-GP staff
      in GP practices on the quality of care for patients with diabetes or
      cardiovascular disease. A cluster randomised trial was undertaken across 60 GP
      practices. The intervention was implemented in 30 practices with staff and
      patients interviewed at baseline and at 12-15 months follow up. The change in
      team roles was evaluated using a questionnaire completed by practice staff. The
      quality of care was evaluated using the Patient Assessment of Chronic Illness
      Care questionnaire. We found that although the team roles of staff improved in
      the intervention practices and there were significant differences between
      practices, there was no significant difference between those in the intervention
      and control groups in patient-assessed quality of care after adjusting for
      baseline-level score and covariates at the 12-month follow up. Practice team
      roles were not significantly associated with change in Patient Assessment of
      Chronic Illness Care scores. Patients with multiple conditions were more likely
      to assess their quality of care to be better. Thus, although previous research
      has shown a cross-sectional association between team work and quality of care, we
      were unable to replicate these findings in the present study. These results may
      be indicative of insufficient time for organisational change to result in
      improved patient-assessed quality of care, or because non-GP staff roles were not
      sufficiently focussed on the aspects of care assessed. The findings provide
      important information for researchers when designing similar studies. 

PMID- 22951282
TI  - The Four Seasons approach to the management of modern HIV medicine in high-income
      countries.

PMID- 22951283
TI  - A general approach for the microrheology of cancer cells by atomic force
      microscopy.
AB  - The determination of the viscoelastic properties of cells by atomic force
      microscopy (AFM) is mainly realized by looking at the relaxation of the force
      when a constant position of the AFM head is maintained or at the evolution of the
      indentation when a constant force is maintained. In both cases the analysis rests
      on the hypothesis that the motion of the probe before the relaxation step is
      realized in a time which is much smaller than the characteristic relaxation time
      of the material. In this paper we carry out a more general analysis of the probe
      motion which contains both the indentation and relaxation steps, allowing a
      better determination of the rheological parameters. This analysis contains a
      correction of the Hertz model for large indentation and also the correction due
      to the finite thickness of the biological material; it can be applied to
      determine the parameters representing any kind of linear viscoelastic model. This
      approach is then used to model the rheological behavior of one kind of cancer
      cell called Hep-G2. For this kind of cell, a power law model does not well
      describe the low and high frequency modulus contrary to a generalized Maxwell
      model.

PMID- 22951284
TI  - Resistance strength training's effects on late components of postural responses
      in the elderly.
AB  - The effect of resistance strength training on different phases of reactive
      postural responses to upright-stance perturbation was assessed in elderly women.
      Perturbation to body balance was produced by fast arm movements aiming at lifting
      different loads in either certain or uncertain contexts. Results from center-of
      pressure analysis showed that lifting a light load under uncertainty led to more
      body sway than under certainty. Resistance strength training led to short periods
      of body sway in the compensation phase and to decreased variability in the
      stabilization phase of postural responses. These results suggest that
      neuromuscular adaptation from resistance strength training benefits late phases
      of postural responses to perturbation of body balance in the elderly.

PMID- 22951286
TI  - TAS-102 in refractory colorectal cancer: caution is needed.

PMID- 22951285
TI  - Comparison of the agar block and Lieber-DeCarli diets to study chronic alcohol
      consumption in an aging model of Fischer 344 female rats.
AB  - INTRODUCTION: Post-menopausal women have a greater risk of developing alcoholic
      complications compared to age-matched men. Unfortunately, animal models of
      chronic ethanol consumption with estrogen deficiency are lacking. Here, we
      characterize the ability of the agar block and Lieber-DeCarli models of chronic
      ethanol consumption to produce elevated blood alcohol content (BAC) and liver
      pathology in the F344 postmenopausal animal model of aging. METHODS: Adult (3 mo)
      and aged (18 mo) F344 ovary-intact or ovariectomized rats were administered
      ethanol for 14-20 weeks as follows: diet 1, standard chow access, 10% ethanol in
      drinking water, and 40% ethanol in agar blocks; diet 2, diet 1 plus low
      phytoestrogen chow (known to affect ethanol metabolism) for the final 4 weeks;
      diet 3, Lieber-DeCarli all liquid diet with 36% kcal ethanol. Control animals
      were matched isocalorically with dextrin. RESULTS: For the agar block diet,
      average BAC was 13+/-4 mg/dL across groups. BAC was unaffected by reducing
      dietary phytoestrogen content (12+/-4 mg/dL), which is known to interfere with
      ethanol metabolism. Liver pathology was unaffected by the agar block diet. In
      contrast, the Lieber-DeCarli diet resulted in BAC of 45+/-5 mg/dL in conjunction
      with more severe hepatopathology.223 DISCUSSION: We conclude that the Lieber
      DeCarli diet produces greater BAC and hepatopathology to study the effects of
      chronic ethanol administration in the F344 postmenopausal rodent model of aging
      when compared to an ethanol agar block diet.

PMID- 22951287
TI  - TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind,
      randomised, placebo-controlled phase 2 trial.
AB  - BACKGROUND: Treatments that confer survival benefit are needed in patients with
      heavily pretreated metastatic colorectal cancer. The aim of this trial was to
      investigate the efficacy and safety of TAS-102-a novel oral nucleoside antitumour
      agent. METHODS: Between August 25, 2009, and April 12, 2010, we undertook a
      multicentre, double-blind, randomised, placebo-controlled phase 2 trial in Japan.
      Eligible patients were 20 years or older; had confirmed colorectal
      adenocarcinoma; had a treatment history of two or more regimens of standard
      chemotherapy; and were refractory or intolerant to fluoropyrimidine, irinotecan,
      and oxaliplatin. Patients had to be able to take oral drugs; have measurable
      lesions; have an Eastern Cooperative Oncology Group performance status of between
      0 and 2; and have adequate bone-marrow, hepatic, and renal functions within 7
      days of enrolment. Patients were randomly assigned (2:1) to either TAS-102 (35
      mg/m(2) given orally twice a day in a 28-day cycle [2-week cycle of 5 days of
      treatment followed by a 2-day rest period, and then a 14-day rest period]) or
      placebo; all patients received best supportive care. Randomisation was done with
      minimisation methods, with performance status as the allocation factor. The
      randomisation sequence was generated with a validated computer system by an
      independent team from the trial sponsor. Investigators, patients, data analysts,
      and the trial sponsor were masked to treatment assignment. The primary endpoint
      was overall survival in the intention-to-treat population. Safety analyses were
      done in the per-protocol population. The study is in progress and is registered
      with Japan Pharmaceutical Information Center, number JapicCTI-090880. FINDINGS:
      112 patients allocated to TAS-102 and 57 allocated to placebo made up the
      intention-to-treat population. Median follow-up was 11.3 months (IQR 10.7-14.0).
      Median overall survival was 9.0 months (95% CI 7.3-11.3) in the TAS-102 group and
      6.6 months (4.9-8.0) in the placebo group (hazard ratio for death 0.56, 80% CI
      0.44-0.71, 95% CI 0.39-0.81; p=0.0011). 57 (50%) of 113 patients given TAS-102 in
      the safety population had neutropenia of grade 3 or 4, 32 (28%) leucopenia, and
      19 (17%) anaemia. No patient given placebo had grade 3 or worse neutropenia or
      leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events
      occurred in 21 (19%) patients in the TAS-102 group and in five (9%) in the
      placebo group. No treatment-related deaths occurred. INTERPRETATION: TAS-102 has
      promising efficacy and a manageable safety profile in patients with metastatic
      colorectal cancer who are refractory or intolerant to standard chemotherapies.

PMID- 22951288
TI  - Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1
      cells.
AB  - Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems,
      was subjected to in vitro experiments to investigate its bioactivities on
      proliferation, differentiation and mineralization of the osteoblastic cell line
      MC3T3-E1. MTT assay, the alkaline phosphatase (ALP) activity and calcium
      deposition were determined, and the secretion of collagen I (COL I), osteocalcin
      (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB
      ligand (RANKL) were also assayed by enzyme-linked immunosorbent assay (ELISA).
      The results showed that ECH caused a significant increase in cell proliferation,
      ALP activity, COL I contents, OCN levels and an enhancement of mineralization in
      osteoblasts at the concentration range from 0.01 to 10nmol.L(-1) (p<0.05),
      suggesting that ECH has a stimulatory effect on osteoblastic bone formation or
      has potential activity against osteoporosis. In addition, the ratio of OPG/RANKL
      also could be enhanced by ECH. These findings provide the potent evidence that
      ECH can promote bone regeneration in cultured osteoblastic MC3T3-E1 cells, which
      might be done by elevating the OPG/RANKL ratio, and potential evidence for
      echinacoside to be a promising drug or a lead compound in the development of
      disease-modifying drug to prevent osteoporosis.

PMID- 22951289
TI  - Quadriceps strength and corticospinal excitability as predictors of disability
      after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Disability is common in a proportion of patients after anterior
      cruciate ligament reconstruction (ACL-R). Neuromuscular quadriceps deficits are a
      hallmark impairment after ACL-R, yet the link between muscle function and
      disability is not understood. PURPOSES: To evaluate the ability of quadriceps
      strength and cortical excitability to predict self-reported disability in
      patients with ACL-R. METHODS: Fifteen participants with a history of ACL-R (11
      female, 4 male; 172 +/- 9.8 cm, 70.4 +/- 17.5 kg, 54.4 +/- 40.9 mo postsurgery)
      were included in this study. Corticospinal excitability was assessed using active
      motor thresholds (AMT), while strength was assessed with maximal voluntary
      isometric contractions (MVIC). Both voluntary strength and corticospinal
      excitability were used to predict disability measured with the International Knee
      Documentation Committee Index (IKDC). RESULTS: The overall multiple-regression
      model significantly predicted 66% of the variance in self-reported disability as
      measured by the IKDC index (R2 = .66, P = .01). Initial imputation of MVIC into
      the model accounted for 61% (R2 = .61, P = .01) of the variance in IKDC. The
      subsequent addition of AMT into the model accounted for an insignificant increase
      of 5% (Delta R2 = .05, P = .19) in the prediction capability of the model.
      CONCLUSIONS: Quadriceps voluntary strength and cortical excitability predicted
      two-thirds of the variance in disability of patients with ACL-R, with strength
      accounting for virtually all of the predictive capability of the model.

PMID- 22951290
TI  - Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and
      HSL expression, and stimulation of lipolysis in adipose tissue.
AB  - Dehydroepiandrosterone (DHEA) reduces body fat in rodents and humans, and
      increases glycerol release from isolated rat epididymal adipocytes and human
      visceral adipose tissue explants. It suggests that DHEA stimulates triglyceride
      hydrolysis in adipose tissue; however, the mechanisms underlying this action are
      still unclear. We examined the effects of DHEA on the expression of adipose
      triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), the key enzymes of
      lipolysis, in rat epididymal white adipose tissue (eWAT). Male Wistar rats were
      fed a diet containing 0.6% DHEA for 2 weeks and eWAT was analyzed for mRNA and
      protein expression of ATGL and HSL, as well as mRNA expression of peroxisome
      proliferator-activated receptor gamma 2 (PPARgamma2) and its downstream target
      fatty acid translocase (FAT). Glycerol release from eWAT explants and serum free
      fatty acids (FFA) were also measured. Rats that received DHEA gained less weight,
      had 23% lower eWAT mass and 31% higher serum FFA levels than controls. Cultured
      explants of eWAT from DHEA-treated rats released 81% more glycerol than those
      from control rats. DHEA administration upregulated ATGL mRNA (1.62-fold, P<0.05)
      and protein (1.78-fold, P<0.05) expression as well as augmented HSL mRNA levels
      (1.36-fold, P<0.05) and Ser660 phosphorylation of HSL (2.49-fold, P<0.05).
      PPARgamma2 and FAT mRNA levels were also increased in DHEA-treated rats (1.61
      fold, P<0.05 and 2.16-fold, P<0.05; respectively). Moreover, ATGL, HSL, and FAT
      mRNA levels were positively correlated with PPARgamma2 expression. This study
      demonstrates that DHEA promotes lipid mobilization in adipose tissue by
      increasing the expression and activity of ATGL and HSL. The effects of DHEA
      appear to be mediated, at least in part, via PPARgamma2 activation, which in turn
      upregulates ATGL and HSL gene expression.

PMID- 22951291
TI  - The activities of 5alpha-reductase and 17,20-lyase determine the direction
      through androgen synthesis pathways in patients with 21-hydroxylase deficiency.
AB  - OBJECTIVE: The 'backdoor' pathway provides an efficient route from 17alpha
      hydroxyprogesterone (17-OHP) to dihydrotestosterone (DHT) in patients with 21
      hydroxylase deficiency (21-OHD). 17-OHP is a good substrate for 5alpha-reductase
      leading to 17alpha-hydroxyallopregnanolone, which is an excellent substrate for
      the 17,20-lyase activity of CYP17A1. 5alpha-Reductase and CYP17A1 are therefore
      two crucial enzymes in the backdoor route. The 17,20-lyase activity of CYP17A1
      additionally promotes the conversion of 17-OHP and 17alpha-hydroxypregnenolone to
      androgens in the classical Delta(4) and Delta(5) pathways. Thus, we hypothesised
      that the activities of 5alpha-reductase and 17,20-lyase should determine the flux
      through the androgen synthesis pathways in patients with 21-OHD. DESIGN AND
      METHODS: We compared retrospectively urinary steroid hormone profiles determined
      by gas chromatography-mass spectrometry of 142 untreated 21-OHD patients (age
      range: 1 day to 25.4 years; 51 males) with 138 control subjects. RESULTS: The
      relative activities of the backdoor pathway and 5alpha-reductase correlated
      significantly (p<0.0001). Neonates with 21-OHD demonstrated a moderate activity
      of the 5alpha-reductase leading to moderate 17alpha-hydroxyallopregnanolone
      generation in the backdoor pathway. Due to substantial 17,20-lyase activity,
      17alpha-hydroxyallopregnanolone is converted rapidly to androsterone. During
      infancy, the activity of 5alpha-reductase is very high leading to a high activity
      of the backdoor pathway until the generation of 17alpha-hydroxyallopregnanolone.
      Only a moderate androsterone production is the result of low 17,20-lyase
      activity. Children show a low 5alpha-reductase and a high 17,20-lyase activity
      leading to a low androsterone generation via the backdoor pathway. CONCLUSION:
      The 5alpha-reductase is the gatekeeper of the backdoor pathway, whereas the 17,20
      lyase activity of CYP17A1 is the regulator of the flux through the androgen
      pathways.

PMID- 22951292
TI  - Treatment options for anal intraepithelial neoplasia and evidence for their
      effectiveness.
AB  - There is a growing range of treatment options for anal intraepithelial neoplasia
      (AIN). In HIV-positive patients, sustained treatment is often required to achieve
      clearance. The treatments considered are topically applied fluorouracil,
      imiquimod, cidofovir and trichloroacetic acid, the potential treatments of
      topical lopinavir and photodynamic therapy with aminolevulenic acid, and the
      surgical methods of electrosurgery, infrared coagulation and laser. Destructive
      treatment methods, possibly including TCA, are more effective than self applied
      topical treatments. Combining or alternating different treatments should be
      considered.

PMID- 22951293
TI  - Computational biotechnology: prediction of competitive substrate inhibition of
      enzymes by buffer compounds with protein-ligand docking.
AB  - In vitro enzymatic activity highly depends on the reaction medium. One of the
      most important parameters is the buffer used to keep the pH stable. The buffering
      compound prevents a severe pH-change and therefore a possible denaturation of the
      enzyme. However buffer agents can also have negative effects on the enzymatic
      activity, such as competitive substrate inhibition. We assess this effect with a
      computational approach based on a protein-ligand docking method and the HYDE
      scoring function. Our method predicts competitive binding of the buffer compound
      to the active site of the enzyme. Using data from literature and new experimental
      data, the procedure is evaluated on nine different enzymatic reactions. The
      method predicts buffer-enzyme interactions and is able to score these
      interactions with the correct trend of enzymatic activities. Using the new
      method, possible buffers can be selected or discarded prior to laboratory
      experiments.

PMID- 22951294
TI  - Serum levels of the hepcidin-20 isoform in a large general population: the Val
      Borbera study.
AB  - Hepcidin, a 25 amino-acid liver hormone, has recently emerged as the key
      regulator of iron homeostasis. Proteomic studies in limited number of subjects
      have shown that biological fluids can also contain truncated isoforms, whose role
      remains to be elucidated. We report, for the first time, data about serum levels
      of the hepcidin-20 isoform (hep-20) in a general population, taking advantage of
      the Val Borbera (VB) study where hepcidin-25 (hep-25) was measured by SELDI-TOF
      MS. Detectable amount of hep-20 were found in sera from 854 out of 1577 subjects
      (54.2%), and its levels were about 14% of hep-25 levels. A small fraction of
      subjects (n=30, 1.9%) had detectable hep-20 but undetectable hep-25. In
      multivariate regression models, significant predictors of hep-20 were hep-25 and
      age in males, and hep-25, age, serum ferritin and body mass index in females. Of
      note, the hep-25:hep-20 ratio was not constant in the VB population, but
      increased progressively with increasing ferritin levels. This is not consistent
      with the simplistic view of hep-20 as a mere catabolic byproduct of hep-25.
      Although a possible active regulation of hep-20 production needs further
      confirmation, our results may also have implications for immunoassays for serum
      hepcidin based on antibodies lacking specificity for hep-25. This article is part
      of a Special Issue entitled: Integrated omics.

PMID- 22951295
TI  - Prohibitin-1 deficiency promotes inflammation and increases sensitivity to liver
      injury.
AB  - Liver diseases are the fifth cause of mortality in Western countries, and as
      opposed to other major causes of mortality, their incidence is increasing.
      Understanding the molecular background contributing to the progression of liver
      ailments will surely open new perspectives for the better management of patients.
      The aim of this study is to elucidate mechanisms underlying the progression of
      liver injury associated with deficient prohibitin 1, an essential protein to
      maintain mitochondrial homeostasis and gene expression. PHB1+/- mice developed a
      more severe steatohepatitis than WT littermates when exposed to a choline and
      methionine deficient diet. The increased sensitivity was mediated by
      mitochondrial dysfunction and metabolic impairment in PHB1+/- livers, including
      inactivation of AMP kinase, measured under a non-restricted diet. Moreover, pro
      inflammatory challenges induced higher mortality and liver injury in PHB+/- mice.
      The increased proliferative capacity of PHB+/- splenocytes, resulting from
      constitutive defects in central molecular pathways as stated by deregulation of
      GSK3beta, Erk, Akt or SHP-1, and the concomitant overproduction of pro
      inflammatory mediators in Phb1 deficient mice, might account for these effects.
      In light of these results it might be concluded that Phb1 deficiency is a
      potential driver of chronic liver diseases by inducing hepatocyte damage and
      inflammation.

PMID- 22951296
TI  - Glucagon receptor is required for long-term survival: a natural history study of
      the Mahvash disease in a murine model.
AB  - BACKGROUND AND AIM: We have described a novel Mahvash disease of
      hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an
      inactivating glucagon receptor mutation, and identified the glucagon receptor
      deficient (Gcgr(-/-)) mice as its murine model. We aim to elucidate the natural
      history of the rare Mahvash disease by long-term observation of the Gcgr(-/-)
      mice. MATERIALS AND METHOD: Wild type (WT) (n=52), heterozygous (n=127), and
      Gcgr(-/-) (n=56) mice living under standard vivarium conditions were observed
      without specific treatments over 22 months. Autopsy was performed on dead
      animals. RESULTS: The WT and heterozygous mice did not exhibit any measurable
      differences. The Gcgr(-/-) mice became progressively lethargic and cachexic after
      12 months. Random glucose levels were stable in WT and heterozygous mice but
      decreased with age in the Gcgr(-/-) mice. At the end of observation, 28/56 Gcgr(
      /-), 7/52 WT, and 24/127 heterozygous mice died. The survival curve of Gcgr(-/-)
      mice began to separate from those of WT and heterozygous mice at 12 months and
      the survival difference widened with age. At 18 months, survival probability was
      17% for Gcgr(-/-) mice but 77% for WT and 81% for heterozygous mice. Autopsy
      revealed numerous PNETs up to 15 mm in diameter in most well-preserved Gcgr(-/-)
      pancreata (17/20) but none in WT or heterozygous ones. Four Gcgr(-/-) mice
      developed liver or subcutaneous metastasis. CONCLUSION: The untreated Mahvash
      disease may cause cachexia, severe hypoglycemia, and early death. Patients with
      Mahvash disease need to undergo life-long surveillance for PNETs. Functional
      glucagon receptor is thus required for long-term survival.

PMID- 22951297
TI  - Interdisciplinary perspectives on the management of the unsettled baby: key
      strategies for improved outcomes.
AB  - The objectives of this study were to analyse the perspectives of key informants
      with clinical expertise in the care of unsettled babies in the first few months
      of life and their families, concerning changes required to improve outcomes. The
      research used a purposive selection strategy and thematic analysis of key
      informant interviews of24 health professionals from 11 disciplines. Informants
      were selected for extensive experience in the management of unsettled babies and
      their families. Participants corroborated existing evidence that post-birth care
      in Australia is fragmented. All held the view that, first, early primary care
      intervention for unsettled infants and their families, and second, improved cross
      professional communication, are vital if the burden of this problem to the
      infant, family and health system are to be minimised. There was consensus, third,
      that significant gaps exist in health professionals' knowledge base and
      management behaviours. The development of education resources, best practice
      guidelines, shared assessment frameworks for primary care practitioners and
      strategies for improved cross-professional communication are necessary to improve
      the health outcomes and decrease the burden of this common yet complex post-birth
      problem.

PMID- 22951299
TI  - Chest CT in infants and children.
AB  - Computed tomography (CT) is a powerful and irreplaceable imaging technique in the
      evaluation of thoracic disease in infants and children. Recent advances in CT
      technology, with multi-detector equipment now widely available in most
      institutions, allowing a highly detailed evaluation of the chest in a short time
      period has resulted in expanding indications of chest CT in paediatric patients.
      Its improved diagnostic yield along with a widespread availability has also
      resulted in an increased number of CT examinations in children, not always with
      beneficial impact on patient management and outcome. Accordingly with the ALARA
      concept, a judicious and correct use of CT is strongly advisable in order to
      reduce unnecessary high dose radiation exposure. The objective of this paper is
      to review the use of chest CT in paediatric patients focused mainly on basic
      technical aspects and clinical applications in the evaluation of the lungs,
      mediastinum and chest wall.

PMID- 22951298
TI  - Imaging tumors of the patella.
AB  - BACKGROUND: Patellar tumors are rare; only a few series have been described in
      the literature and radiographic diagnosis can be challenging. We reviewed all
      patellar tumors at one institution and reviewed the literature. MATERIALS AND
      METHODS: In an evaluation of the database at one institution from 1916 to 2009,
      23,000 bone tumors were found. Of these, 41 involved the patella. All had imaging
      studies and microscopic diagnostic confirmation. All medical records, imaging
      studies, and pathology were reviewed. RESULTS: There were 15 females and 26
      males, ranging from 8 to 68 years old (average 30). There were 30 benign tumors;
      eight giant cell tumors, eight chondroblastomas, seven osteoid osteomas, two
      aneurysmal bone cysts, two ganglions, one each of chondroma, exostosis, and
      hemangioma. There were 11 malignant tumors: five hemangioendotheliomas, three
      metastases, one lymphoma, one plasmacytoma, and one angiosarcoma. CONCLUSION:
      Patellar tumors are rare and usually benign. As the patella is an apophysis, the
      most frequent lesions are giant cell tumor in the adult and chondroblastoma in
      children. Osteoid osteomas were frequent in our series and easily diagnosed.
      Metastases are the most frequent malignant diagnoses in the literature; in our
      series malignant vascular tumors were more common. These lesions are often easily
      analyzed on radiographs. CT and MR define better the cortex, soft tissue
      extension, and fluid levels. This study presents the imaging patterns of the more
      common patellar tumors in order to help the radiologist when confronted with a
      lesion in this location.

PMID- 22951300
TI  - D-dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in
      preadipocytes.
AB  - We previously identified D-dopachrome tautomerase (DDT) as a novel adipokine
      whose mRNA levels in adipocytes are negatively correlated with obesity-related
      clinical parameters, and which acts on adipocytes to regulate lipid metabolism.
      Here we investigated functions of DDT on preadipocytes. Recombinant DDT (rDDT)
      enhanced both the expression and secretion of interleukin-6 (IL-6) in SGBS cells,
      a human preadipocyte cell line. Treatment with rDDT increased levels of
      phosphorylated ERK1/2, but not p38, in SGBS cells, and rDDT-induced IL-6 mRNA
      expression was attenuated by pretreatment with an ERK inhibitor, U0126. Knockdown
      of CD74, but not CD44, inhibited rDDT-induced IL-6 mRNA expression in SGBS cells.
      These results suggested that the rDDT-induced IL-6 expression in preadipocytes
      occurred through the CD74-ERK pathway. Furthermore, in SGBS cells subjected to
      adipogenic induction, rDDT decreased the amount of triacylglycerol, number of
      cells with oil droplets, and levels of mRNA encoding adipocyte marker proteins.
      Increased expression of CCAAT/enhancer binding protein families and peroxisome
      proliferator-activated receptor gamma2 during adipogenesis was inhibited in the
      cells treated with rDDT. These results suggested DDT to inhibit adipogenesis by
      suppressing the expression of genes encoding adipogenic regulators in
      preadipocytes.

PMID- 22951301
TI  - Couch-based motion compensation: modelling, simulation and real-time experiments.
AB  - The paper presents a couch-based active motion compensation strategy evaluated in
      simulation and validated experimentally using both a research and a clinical
      Elekta Precise TableTM. The control strategy combines a Kalman filter to predict
      the surrogate motion used as a reference by a linear model predictive controller
      with the control action calculation based on estimated position and velocity
      feedback provided by an observer as well as predicted couch position and velocity
      using a linearized state space model. An inversion technique is used to
      compensate for the dead-zone nonlinearity. New generic couch models are presented
      and applied to model the Elekta Precise TableTM dynamics and nonlinearities
      including dead zone. Couch deflection was measured for different manufacturers
      and found to be up to 25 mm. A feed-forward approach is proposed to compensate
      for such couch deflection. Simultaneous motion compensation for longitudinal,
      lateral and vertical motions was evaluated using arbitrary trajectories generated
      from sensors or loaded from files. Tracking errors were between 0.5 and 2 mm RMS.
      A dosimetric evaluation of the motion compensation was done using a sinusoidal
      waveform. No notable differences were observed between films obtained for a fixed
      or motion-compensated target. Further dosimetric improvement could be made by
      combining gating, based on tracking error together with beam on/off time, and PSS
      compensation.

PMID- 22951302
TI  - Naturally occurring infections of cattle with Theileria lestoquardi and sheep
      with Theileria annulata in the Sudan.
AB  - Theileria annulata is endemic in northern Sudan, hindering all efforts at
      upgrading cattle for milk production. T. lestoquardi clinical cases occur
      throughout the year and causes annual outbreaks that result in substantial losses
      in sheep. In the northern Sudan both cattle and small ruminants are frequently
      raised together and/or share common grazing grounds at river banks. In an attempt
      to evaluate field cross infectivity of Theileria lestoquardi and T. annulata in
      cattle and sheep respectively, a PCR analysis was carried out on samples
      collected from closely reared sheep and cattle using both T. annulata and T.
      lestoquardi specific primers. A total of 19 sheep out of 51 (37.3%) were positive
      for T. lestoquardi while four sheep (7.8%) showed T. annulata specific amplicons.
      A total of 38 out of 52 (73.1%) surveyed cattle were PCR positive for T. annulata
      and only two (3.8%) showed T. lestoquardi specific bands. These findings indicate
      complex epidemiology of both infections in areas where both parasites are
      transmitted by the same vector and call for further investigations of this
      phenomenon.

PMID- 22951303
TI  - Prevalence and distribution of Clostridium difficile PCR ribotypes in cats and
      dogs from animal shelters in Thuringia, Germany.
AB  - Clostridium difficile is an important cause of nosocomial diarrhoea in humans.
      Pet animals and livestock are discussed as potential natural reservoirs and
      sources of infection. In this study faecal samples from dogs and cats were
      collected at 10 animal shelters in Thuringia, Germany. C. difficile was isolated
      from 9 out of 165 (5.5%) canine and 5 out of 135 (3.7%) feline samples. Five PCR
      ribotypes (010, 014/020, 039, 045, SLO 066) were identified. PCR ribotypes 010
      and 014/020 were detected in more than one shelter and PCR ribotypes 014/020 and
      045 were isolated from dogs and cats. MLVA profiles of strains of a PCR ribotype
      from one shelter were identical or closely related, while strains of the same PCR
      ribotype from different shelters showed significant differences. This study shows
      that dogs and cats kept in animal shelters are a reservoir of C. difficile PCR
      ribotypes which can infect also humans.

PMID- 22951304
TI  - EXAMINATION of new drug-eluting stents--top of the class!

PMID- 22951305
TI  - Everolimus-eluting stent versus bare-metal stent in ST-segment elevation
      myocardial infarction (EXAMINATION): 1 year results of a randomised controlled
      trial.
AB  - BACKGROUND: Everolimus-eluting stent (EES) reduces the risk of restenosis in
      elective percutaneous coronary intervention. However, the use of drug-eluting
      stent in patients with ST-segment elevation myocardial infarction (STEMI) is
      still controversial. Data regarding the performance of second-generation EES in
      this setting are scarce. We report the 1-year result of the EXAMINATION (clinical
      Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing
      EES with bare-metal stents (BMS) in patients with STEMI. METHODS: This
      multicentre, prospective, randomised, all-comer controlled trial was done in 12
      medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we
      recruited patients with STEMI up to 48 h after the onset of symptoms requiring
      emergent percutaneous coronary intervention. Patients were randomly assigned
      (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six
      patients, stratified by centre and centralised by telephone. Patients were masked
      to treatment. The primary endpoint was the patient-oriented combined endpoint of
      all-cause death, any recurrent myocardial infarction, and any revascularisation
      at 1 year and was analysed by intention to treat. The secondary endpoints of the
      study included the device-oriented combined endpoint of cardiac death, target
      vessel myocardial infarction or target lesion revascularisation, and rates of all
      cause or cardiac death, recurrent myocardial infarction, target lesion or target
      vessel revascularisation, stent thrombosis, device and procedure success, and
      major and minor bleeding. This trial is registered with ClinicalTrials.gov,
      number NCT00828087. FINDINGS: Of the 1504 patients randomised, 1498 patients were
      randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was
      similar in both groups (89 [11.9%] of 751 patients in the EES group vs 106
      [14.2%] of 747 patients in the BMS group; difference -2.34 [95% CI -5.75 to
      1.07]; p=0.19). Device-oriented endpoint (44 [5.9%] in the EES group vs 63 [8.4%]
      in the BMS group; difference -2.57 [95% CI -5.18 to 0.03]; p=0.05) did not differ
      between groups, although rates of target lesion and vessel revascularisation were
      significantly lower in the EES group (16 [2.1%] vs 37 [5.0%], p=0.003, and 28
      [3.7%] vs 51 [6.8%], p=0.0077, respectively). Rates of all cause (26 [3.5%] for
      EES vs 26 [3.5%] for BMS, p=1.00) or cardiac death (24 [3.2%] for EES vs 21
      [2.8%] for BMS, p=0.76) or myocardial infarction (10 [1.3%] vs 15 [2.0%], p=0.32)
      did not differ between groups. Stent thrombosis rates were significantly lower in
      the EES group (4 [0.5%] patients with definite stent thrombosis in the EES group
      vs 14 [1.9%] in the BMS group and seven [0.9%] patients with definite or probable
      stent thrombosis in the EES group vs 19 [2.5%] in the BMS group, both p=0.019).
      Although device success rate was similar between groups, procedure success rate
      was significantly higher in the EES group (731 [97.5%] vs 705 [94.6%]; p=0.0050).
      Finally, Bleeding rates at 1 year were comparable between groups (29 [3.9%]
      patients in the EES group vs 39 [5.2%] in the BMS group; p=0.19). INTERPRETATION:
      The use of EES compared with BMS in the setting of STEMI did not lower the
      patient-oriented endpoint. However, at the stent level both rates of target
      lesion revascularisation and stent thrombosis were reduced in recipients of EES.
      FUNDING: Spanish Heart Foundation.

PMID- 22951306
TI  - Clostridium difficile detection: identification of colonization, subclinical and
      overt disease.

PMID- 22951307
TI  - Test-retest reliability and validity of isometric knee-flexion and -extension
      measurement using 3 methods of assessing muscle strength.
AB  - CONTEXT: Physicians and clinicians need portable, efficient, and cost-effective
      assessment tools to determine the effectiveness of rehabilitation programs after
      knee injury. Progress in rehabilitation should be evaluated using valid and
      reliable measurement methods. OBJECTIVE: To examine the test-retest reliability
      of portable fixed dynamometry (PFD), handheld dynamometry (HHD), and isokinetic
      dynamometry (IKD). In addition, the authors sought to examine the validity of PFD
      and HHD by comparing differences in peak torque of the knee flexors and extensors
      to that of the "gold standard" IKD. DESIGN: Repeated measures. PARTICIPANTS: 16
      healthy subjects (age 29.3 +/- 7.2 y, height 167.4 +/- 8.04 cm, mass 73.7 +/-
      20.0 kg). MAIN OUTCOME MEASURES: The dependent variables were peak torque
      (normalized to body weight) of the knee flexors and extensors; the independent
      variables were trial (trial 1, trial 2) and instrument (IKD, PFD, and HHD).
      RESULTS: Test-retest reliability was high for both PFD and IKD. However, fair to
      poor reliability was found for HHD. There were no differences in peak torque (Nm)
      between IKD and PFD. However, significant differences in peak torque were
      observed between IKD and HHD and between PFD and HHD. CONCLUSIONS: PFD provides
      reliable measures of strength and also demonstrates similar output measures as
      IKD. Its portability, ease of use, and cost provide clinicians an effective means
      of measuring strength.

PMID- 22951308
TI  - Application of IL-2 therapy to target T regulatory cell function.
AB  - Interleukin-2 (IL-2) was originally discovered as a growth factor for activated T
      cells in vitro. IL-2 promotes CD8(+) T cell growth and differentiation in vivo,
      but has little effect on CD4(+) T cell function. Regulatory T cells (Treg cells)
      express all three chains (CD25, CD122, and CD132) of the IL-2 receptor complex
      and are dependent on IL-2 for survival and function. Exogenous IL-2 can augment
      Treg cell numbers in vivo and may have therapeutic value in the treatment of
      autoimmune and inflammatory diseases. Complexes of IL-2 with different IL-2
      antibodies can target delivery to cells expressing all three receptor chains
      (Treg cells and activated T effector cells) or to cells expressing just CD122 and
      CD132 (NK cells and memory phenotype CD8(+) T cells).

PMID- 22951310
TI  - Interaction of cellular poly(C)-binding protein 2 with nonstructural protein
      1beta is beneficial to Chinese highly pathogenic porcine reproductive and
      respiratory syndrome virus replication.
AB  - Non-structural protein1beta (Nsp1beta) of porcine reproductive and respiratory
      syndrome virus (PRRSV) has been recognized to be involved in suppressing the host
      innate immune response and mediating viral subgenomic mRNA transcription. In the
      present study, we have analyzed the interaction of Nsp1beta of Chinese highly
      pathogenic PRRSV (HP-PRRSV) with cellular poly(C)-binding 2 (PCBP2) by means of
      the yeast two-hybrid screening in a pulmonary alveolar macrophages (PAMs) cDNA
      library and co-immunoprecipitation (Co-IP) assay. Our results indicated that the
      Nsp1beta of the HP-PRRSV is able to bind and interact with cellular PCBP2
      strongly in both the infected cells and plasmid transfected cells. Their minimal
      binding regions were identified to be the residues 85-203 aa (PCPbeta and CTE
      domains) for the Nsp1beta and the residues 96-168 aa (KH2 domain) for PCBP2,
      respectively. Next, we used confocal immunofluorescence analysis and discovered
      that, during PRRSV infection in MARC-145 cells and/or plasmid-transfected cells,
      the Nsp1beta and PCBP2 mainly colocalized in the cytoplasm and perinuclear
      pattern. Moreover, the siRNA-mediated silencing of PCBP2 gene in the MARC-145
      cells resulted in significant reduction of the virus titer in supernatants as
      well as viral proteins, while no significant effects on the expression of the
      type I interferon alpha and interferon beta, suggesting that the interaction of
      the Nsp1beta with cellular PCBP2 is beneficial to Chinese HP-PRRSV replication in
      MARC-145 cells.

PMID- 22951309
TI  - Endogenous modulators of inflammatory cell recruitment.
AB  - Leukocyte recruitment is a central immune process. Multiple factors have been
      described to promote leukocyte infiltration into inflamed tissues, but only
      recently has evidence for endogenous negative modulators of this inflammatory
      process emerged. The discovery of several locally produced modulators has emerged
      into a new field of endogenous inhibitors of leukocyte extravasation. Recent
      findings from several inflammatory disease models show that tissues can self
      regulate the recruitment of inflammatory cells, suggesting that local tissues may
      have a greater 'regulatory say' over the immune response than previously
      appreciated. Here, we propose that locally produced modulators of leukocyte
      recruitment may represent local homeostatic mechanisms that tissues and organs
      may have evolved for protection against the destructive potential of the immune
      system.

PMID- 22951311
TI  - A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein
      for the immunotherapy of HPV-associated cancers.
AB  - Development of effective therapeutic vaccines against human papilloma virus (HPV)
      infections remains a priority, considering the high number of new cases of
      cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines
      expressing the E7 oncoprotein, which is detectable in all HPV-positive pre
      cancerous and cancer cells, might clear already established tumors and support
      the treatment of HPV-related lesions. In this study, DNA or fowlpox virus
      recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein
      (DNA(E7GGG) and FP(E7GGG)) were generated. Two immunization regimens were tested
      in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP)
      prime-boost protocols to evaluate the immune response and therapeutic efficacy of
      the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were
      elicited after immunization, and in vivo experiments resulted in a higher number
      of tumor-free mice after the heterologous immunization. These results establish a
      preliminary indication for therapy of HPV-related tumors by the combined use of
      DNA and avipox recombinants, which might represent safer immunogens than vaccinia
      based vaccines.

PMID- 22951312
TI  - Mapping interactions of Chikungunya virus nonstructural proteins.
AB  - The four nonstructural proteins (nsPs1-4) of Chikungunya virus (CHIKV) play
      important roles involving enzymatic activities and specific interactions with
      both viral and host components, during different stages of viral pathogenesis.
      Elucidation of the presence and/or absence of interactions among nsPs in a
      systematic manner is thus of scientific interest. In the current study, each pair
      wise combination among the four nonstructural proteins of CHIKV was
      systematically analyzed for possible interactions. Six novel protein interactions
      were identified for CHIKV, using systems such as yeast two-hybrid, GST pull down
      and ELISA, three of which have not been previously reported for the genus
      Alphavirus. These interactions form a network of organized associations that
      suggest the spatial arrangement of nonstructural proteins in the late replicase
      complex. The study identified novel interactions as well as concurred with
      previously described associations in related alphaviruses.

PMID- 22951313
TI  - Differences in mortality for surgical cancer patients by insurance and hospital
      safety net status.
AB  - Recent research suggests hospitals serving low-income patients have poorer
      outcomes. However, safety net hospitals (SNHs) offering access to care regardless
      of insurance coverage may provide better care than low-income patients would
      otherwise receive. This study considers the association between insurance and
      mortality among surgical cancer patients and the role of SNHs. We estimate models
      of 1- and 5-year mortality on insurance, SNH status, patient characteristics, and
      hospital surgical volume for colorectal and breast cancer patients. Interaction
      terms between insurance and SNH status estimate how mortality differs by
      insurance source at SNHs. Medicaid and uninsurance are associated with
      significantly higher mortality for colorectal cancer patients. There is a
      statistically significant improvement in mortality for Medicaid colorectal cancer
      patients treated in SNHs relative to non-SNHs and a marginally significant
      improvement for uninsured breast cancer patients treated in SNHs. The results
      suggest a survival benefit for low-income patients treated in SNHs.

PMID- 22951314
TI  - Use of specialty OB consults during high-risk pregnancies in a Medicaid-covered
      population: initial impact of the Arkansas ANGELS intervention.
AB  - This study examines the impact of a Medicaid-supported intervention (Antenatal
      and Neonatal Guidelines, Education and Learning System) to expand a high-risk
      obstetrics consulting service on the use of specialty consults between 2001 and
      2006. Using a Medicaid claims-birth certificate data set, we find a decline over
      time in use of specialty consults for lower risk diagnoses and a shift to remote
      modalities for contact. Local physician participation in grand rounds via
      teleconference was associated both with specialty contact and use of remote
      modalities. Local physician use of a Call Center service was also associated with
      patient specialty contact. Expansion of telemedicine remote sites did not
      increase the likelihood of contact but was associated with the shift toward
      remote modalities. Specialty consult use and modality were influenced by the care
      context of the patient, particularly level of pregnancy risk, the specialty of
      the primary prenatal care provider, the timing of her prenatal care, and her
      ethnicity and education level.

PMID- 22951315
TI  - An unusual endoscopic finding in a patient with melena: multiple gastric ulcers
      of regular shape.

PMID- 22951316
TI  - Disruption of a patellar tendon repair.
AB  - The patient was a 38-year-old man evaluated by a physical therapist 14 weeks
      after repair of the left patellar tendon. The physical therapist requested
      radiographs, which revealed findings consistent with a patellar tendon retear.
      The radiologist recommended further evaluation with magnetic resonance imaging,
      which showed a left patellar tendon tear.

PMID- 22951317
TI  - A rapid LC-ESI-MS/MS method for the quantitation of choline, an active metabolite
      of citicoline: Application to in vivo pharmacokinetic and bioequivalence study in
      Indian healthy male volunteers.
AB  - A rapid, simple, and sensitive high performance liquid chromatography-tandem mass
      spectrometry method (LC-ESI-MS/MS) was developed and validated for the
      determination and pharmacokinetic investigation of choline (CL), active
      metabolite of citicoline in human plasma using metformin (MF) as IS. The
      chromatographic separation was performed on a reversed-phase Phenomenx Gemini C18
      column with a mobile phase of methanol:water (containing 10mM ammonium formate)
      (9:1, v/v). The calibration curves were linear over the range of 0.05-5MUg/ml.
      The validated LC-ESI-MS/MS method was successfully applied for the evaluation of
      pharmacokinetic parameters and bioequivalence study of test and reference control
      release (CR) tablet preparation of citicoline 1000mg after a single oral
      administration to all 12 healthy male volunteers.

PMID- 22951318
TI  - Approach to dose definition to the gross tumor volume for lung cancer with
      respiratory tumor motion.
AB  - The purpose of this study was to validate the dose prescription defined to the
      gross tumor volume (GTV) 3D and 4D dose distributions of stereotactic
      radiotherapy for lung cancer. Treatment plans for 94 patients were generated
      based on computed tomography (CT) under free breathing. A uniform margin of 8 mm
      was added to the internal target volume (ITV) to generate the planning target
      volume (PTV). A leaf margin of 2 mm was added to the PTV. The prescription dose
      was defined such that 99% of the GTV should receive 100% of the dose using the
      Monte Carlo calculation (iPlan RT Dose(TM)) for 6-MV photon beams. The 3D dose
      distribution was determined using CT under free breathing. The 4D dose
      distribution plan was recalculated to investigate the effect of tumor motion
      using the same monitor units as those used for the 3D dose distribution plan. D99
      (99% of the GTV) in the 4D plan was defined as the average D99 in each of the
      four breathing phases (0%, 25%, 50% and 75%). The dose difference between maximum
      and minimum at D99 of the GTV in 4D calculations was 0.6 +/- 1.0% (range 0.2
      4.6%). The average D99 of the GTV from 4D calculations in most patients was
      almost 100% (99.8 +/- 1.0%). No significant difference was found in dose to the
      GTV between 3D and 4D dose calculations (P = 0.67). This study supports the
      clinical acceptability of treatment planning based on the dose prescription
      defined to the GTV.

PMID- 22951319
TI  - In vitro stemness characterization of radio-resistant clones isolated from a
      medulloblastoma cell line ONS-76.
AB  - One-third of patients with medulloblastoma die due to recurrence after various
      treatments including radiotherapy. Although it has been postulated that cancer
      stem-like cells are radio-resistant and play an important role in tumor
      recurrence, the "stemness" of medulloblastoma cells surviving irradiation has not
      yet been elucidated. Using a medulloblastoma cell line ONS-76, cells that
      survived gamma irradiation were investigated on their "stemness" in vitro. From
      10 500 cells, 20 radio-resistant clones were selected after gamma ray irradiation
      (5 Gy * two fractions) using the replica micro-well technique. These 20 resistant
      clones were screened for CD133 positivity by flow cytometry followed by side
      population assay, tumor sphere formation assay and clonogenic survival assay.
      Results revealed CD133 fractions were significantly elevated in three clones,
      which also exhibited significantly increased levels of tumor sphere formation
      ability and side population fraction. Clonogenic survival assay demonstrated that
      their radio-resistance was significantly higher than the parental ONS-76. This
      may support the hypothesis that a small number of cancer stem-like cells (CSCs)
      are the main culprits in local recurrence after radiotherapy, and disruption of
      the resistance mechanism of these CSCs is a critical future issue in improving
      the outcome of patients with medulloblastoma.

PMID- 22951321
TI  - Inflammation and apoptosis in malignant transformation of sinonasal inverted
      papilloma: the role of the bridge molecules, cyclooxygenase-2, and nuclear factor
      kappaB.
AB  - PURPOSE: This study examined the early events in the neoplastic progression of
      the sinonasal inverted papilloma to squamous cell carcinoma from the viewpoint of
      chronic inflammation and apoptosis. MATERIALS AND METHODS: In total, 118 archival
      slides stained with hematoxylin and eosin from 45 patients were graded according
      to histopathology (grades I-IV). Their representative portions were transferred
      to a tissue microarray, sections of which were stained immunohistochemically for
      cyclooxygenase-2, p53, bax, bcl-2, and nuclear factor kappaB. RESULTS:
      Cyclooxygenase-2 expression was positively correlated with histopathologic grade,
      with higher expression in advanced grades. p53s were detected in all cores from
      advanced grades (III, IV), but not in early grades (I, II). The expressions of
      nuclear factor kappaB, bax, and bcl-2 were not correlated with the grade.
      CONCLUSIONS: A p53 mutation seems be a critical event for the malignant
      transformation of the sinonasal inverted papilloma. Cyclooxygenase-2-mediated
      inflammatory signals, activated as a consequence of the p53 mutation, may
      contribute to promoting the proliferation of the advanced sinonasal inverted
      papilloma.

PMID- 22951320
TI  - Selective local delivery of RANK siRNA to bone phagocytes using bone augmentation
      biomaterials.
AB  - Fracture healing and fracture fixation in the context of osteoporosis is
      extremely difficult. To inhibit osteoclast-induced bone resorption and associated
      implant loosening in this pathology, we describe a local delivery strategy to
      delivery RNA interfering technology to bone sites to target and down-regulate
      osteoclast formation and function. Resorbable polymer, poly(lactic-co-glycolic
      acid) (PLGA) microparticles were exploited as a passive phagocyte-targeting
      carrier to deliver RANK siRNA to both osteoclast precursors and osteoclasts - the
      professional phagocytes in bone. These natural phagocytes internalize micron
      sized particles while most other non-targeted cells in bone cannot. PLGA-siRNA
      microparticles were dispersed within biomedical grade calcium-based injectable
      bone cement clinically used in osteoporosis as a bone augmentation biomaterial
      for fragility fracture prevention and fixation. siRNA released from this
      formulation in vitro retains bioactivity against the cell target, RANK, in
      cultured osteoclast precursor cells, inhibiting their progression toward the
      osteoclastic phenotype. These data support the proof-of-concept to utilize a
      clinically relevant approach to locally deliver siRNA to phagocytes in bone and
      improve fragility fracture healing in the context of osteoporosis. This local
      delivery system delivers siRNA therapeutics directly to osteoporosis sites from
      clinically familiar injected bone augmentation materials but could be extended to
      other injectable biomaterials for local siRNA delivery.

PMID- 22951322
TI  - Effects of endokinin A/B and endokinin C/D on the antinociception properties of
      hemopressin in mice.
AB  - The current study evaluated the effects of hemopressin (HP) on pain modulation by
      endokinin A/B (EKA/B) and endokinin C/D (EKC/D) at the supraspinal level in mice.
      Intracerebroventricular administration of HP (10 nmol) fully antagonized the
      hyperalgesia induced by EKA/B (10, 30, and 100 pmol), and induced a dose
      dependent potent analgesic effect. HP at different concentrations (10 pmol, 100
      pmol, and 1 nmol) showed varying effects on the analgesic effect of EKA/B (3
      nmol). HP extended the duration of the analgesic effect of EKC/D (3 nmol).
      Moreover, HP at different concentrations (10 pmol, 5 pmol, 1 pmol, and 100 fmol)
      co-administered with EKC/D (30 pmol) induced significant analgesia at two
      different time points: 5 min and 50 min. To investigate the antinociceptive
      mechanism, we used SR140333B and SR142801. HP (1 pmol) potentiated the analgesic
      effect of SR140333B (100 pmol)+EKA/B (30 pmol) in 5-10 min, while HP (100 pmol)
      had no effect in the analgesia induced by SR140333B (3 nmol)+EKA/B (3 nmol). HP
      (1 nmol) fully inhibited the analgesic effect of SR140333B (3 nmol)+EKC/D (3
      nmol) or SR142801 (3 nmol)+EKC/D (3 nmol). HP (1 pmol) weakened the analgesic
      effect of SR142801 (100 pmol)+EKA/B (30 pmol), but HP (100pmol) strengthened the
      analgesic effect of SR142801 (3 nmol)+EKA/B (3 nmol). These findings may pave the
      way for a new strategy on investigating the interaction between tachykinins and
      opioids on pain modulation.

PMID- 22951323
TI  - Characterization of diverse antimicrobial peptides in skin secretions of Chungan
      torrent frog Amolops chunganensis.
AB  - We have cloned, synthesized, and characterized 11 novel antimicrobial peptides
      from a skin derived cDNA library of the Chungan torrent frog, Amolops
      chunganensis. Seven of the 11 antimicrobial peptides were present in authentic A.
      chunganensis skin secretions. Sequence analysis indicated that the 11 peptides
      belonged to the temporin, esculentin-2, palustrin-2, brevinin-1, and brevinin-2
      families. The peptides displayed potent antimicrobial activities against several
      strains of microorganisms. One peptide, brevinin-1CG5, demonstrated antimicrobial
      activity against all tested Gram-positive and Gram-negative bacteria and fungi,
      and showed high antimicrobial potency (MIC=0.6 MUM) against Gram-positive
      bacterium Rhodococcus rhodochrous. Some peptides also demonstrated weak hemolytic
      activity against human erythrocytes in vitro. Phylogenetic analysis based on the
      amino acid sequences of brevinin-1, brevinin-2, and esculentin-2 peptides from
      family Ranidae confirmed that the current taxonomic status of A. chunganensis is
      correct.

PMID- 22951324
TI  - Regulated granule trafficking in platelets and neurons: a common molecular
      machinery.
AB  - Platelet function in primary hemostasis involves the secretion of granules upon
      activation, providing the localized delivery of effector proteins at sites of
      vascular injury. The sequential process of regulated secretion in platelets, from
      the biogenesis of the granules, through their transport and up to the exocytotic
      fusion process at the acceptor membrane, involves a complex molecular machinery
      conserved between some other specialized cells such as neurons. Mutations in
      genes encoding proteins involved in this process of granule trafficking have
      helped towards demystification of the underlying secretory mechanisms. Human
      diseases of trafficking encompass a broad symptomatology including a platelet
      related bleeding diathesis and neuronal problems. In this review, we want to
      highlight the similarities in granule biology between platelets and neurons and
      further focus on some granule trafficking disorders that result in bleeding and
      neuropathology. This review provides evidence that platelet research can be
      expanded from traditional studies of isolated thrombopathies to the field of
      neuropathologies that include a platelet secretion defect.

PMID- 22951325
TI  - Comparison of the performance of anal cytology and cervical cytology as screening
      tests.
AB  - Cervical cytology screening has a long history and has successfully reduced the
      impact of cervical cancer in many countries. Anal cytology is a relative newcomer
      and anal screening is currently offered in only a few centres around the world.
      Many questions need to be answered before anal screening is more widely adopted.
      While there are many similarities between cervical and anal squamous cell
      carcinoma, there are also important differences: differences in the prevalence of
      disease, in the 'at-risk' target populations and possibly in the robustness of
      the reference standard of biopsy. The performance of cytology as a screening test
      in the literature varies widely but it is essential to understand that some of
      this variability is due to differences in the definitions of key parameters in
      the various studies. For cervical screening, estimates of sensitivity have ranged
      from 19% to 94% and specificity from 94% to 98%. For anal screening, data are
      fewer and more limited. Estimates of the sensitivity of anal cytology in men who
      have sex with men and HIV-positive populations have ranged from 55% to 87% and
      specificity from 37% to 76%. Ultimately, rather than comparing anal with cervical
      cytology, it may be more helpful to assess the value of anal cytology
      independently through well designed trials.

PMID- 22951326
TI  - Kinetic parameter estimation using a closed-form expression via integration by
      parts.
AB  - Dynamic emission computed tomographic imaging with compartment modeling can
      quantify in vivo physiologic processes, eliciting more information regarding
      underlying molecular disease processes than is obtained from static imaging.
      However, estimation of kinetic rate parameters for multi-compartment models can
      be computationally demanding and problematic due to local minima. A number of
      techniques for kinetic parameter estimation have been studied and are in use
      today, generally offering a tradeoff between computation time, robustness of fit
      and flexibility with differing sets of assumptions. This paper presents a means
      to eliminate all differential operations by using the integration-by-parts method
      to provide closed-form formulas, so that the mathematical model is less sensitive
      to data sampling and noise. A family of closed-form formulas are obtained.
      Computer simulations show that the proposed method is robust without having to
      specify the initial condition.

PMID- 22951330
TI  - Hartmannella vermiformis can promote proliferation of Candida spp. in tap-water.
AB  - Candida yeasts colonize humans' oral cavities as commensals or opportunistic
      pathogens. They may be isolated from water circulating in dental unit waterlines
      mixed with saliva traces mainly because of dysfunction of anti-retraction valves.
      Free-living amoebae (FLA), like Hartmannella vermiformis, are frequently found in
      aquatic environments and they have also been already isolated from dental unit
      waterlines. They can be implicated as reservoir for pathogens or directly in
      infections. This work deals with the survival of three species of Candida
      (Candida albicans, Candida glabrata and Candida parapsilosis), in co-cultivation
      with FLA in tap-water. One strain of each Candida species was studied.
      Microbiological and microscopic approaches were used; amoebae-yeasts co
      cultivation assays were performed at different temperatures of incubation.
      Results have shown that H. vermiformis were able to internalize Candida yeasts
      and promote their proliferation in tap-water with or without saliva traces (2%
      v/v). Amoebae interact differently with Candida depending on the temperature used
      and the studied species of yeasts. In conclusion, this study emphasizes the
      survival of yeasts and/or FLA in tap-water. The ability of yeasts and amoebae to
      interact should be taken into account because it could lead to candidiasis
      infection for the frailest patients after a dental treatment.

PMID- 22951329
TI  - Kinetic model of excess activated sludge thermohydrolysis.
AB  - Thermal hydrolysis of excess activated sludge suspensions was carried at
      temperatures ranging from 423 K to 523 K and under pressure 0.2-4.0 MPa. Changes
      of total organic carbon (TOC) concentration in a solid and liquid phase were
      measured during these studies. At the temperature 423 K, after 2 h of the
      process, TOC concentration in the reaction mixture decreased by 15-18% of the
      initial value. At 473 K total organic carbon removal from activated sludge
      suspension increased to 30%. It was also found that the solubilisation of
      particulate organic matter strongly depended on the process temperature. At 423 K
      the transfer of TOC from solid particles into liquid phase after 1 h of the
      process reached 25% of the initial value, however, at the temperature of 523 K
      the conversion degree of 'solid' TOC attained 50% just after 15 min of the
      process. In the article a lumped kinetic model of the process of activated sludge
      thermohydrolysis has been proposed. It was assumed that during heating of the
      activated sludge suspension to a temperature in the range of 423-523 K two
      parallel reactions occurred. One, connected with thermal destruction of activated
      sludge particles, caused solubilisation of organic carbon and an increase of
      dissolved organic carbon concentration in the liquid phase (hydrolysate). The
      parallel reaction led to a new kind of unsolvable solid phase, which was further
      decomposed into gaseous products (CO(2)). The collected experimental data were
      used to identify unknown parameters of the model, i.e. activation energies and
      pre-exponential factors of elementary reactions. The mathematical model of
      activated sludge thermohydrolysis appropriately describes the kinetics of
      reactions occurring in the studied system.

PMID- 22951331
TI  - ANCA vasculitis in a patient with systemic sclerosis.

PMID- 22951332
TI  - Significance of Helicobacter pylori vacA intermediate region genotyping-a
      Bulgarian study.
AB  - The significance of the intermediate (i) region of the Helicobacter pylori vacA
      gene as a virulence factor associated with the severity of gastric disease is
      still disputable. The aim of the present study was to evaluate the prevalence and
      significance of vacA i alleles alone or in combination with other vacA alleles in
      symptomatic Bulgarian patients and to find out possible associations between vacA
      i genotype and patients' disease, age, sex, and other H. pylori virulence
      factors. Unlike vacA s1 and m1, vacA i1 prevalence was significantly higher
      (75.0%) in strains from peptic ulcer patients than in strains from nonulcer
      patients with gastric diseases (58.6%) (P = 0.022). Less virulent vacA s1 i2 m2
      strains were more prevalent in females (P = 0.03), and cagA(+) was associated
      with vacA i1, s1, m1, and their combinations. In conclusion, vacA i status is a
      better predictor for the strain virulence than other vacA alleles.

PMID- 22951333
TI  - Gaze behaviour in social blushers.
AB  - Gaze aversion could be a central component of social phobia. Fear of blushing is
      a symptom of social anxiety disorder (SAD) but is not yet described as a specific
      diagnosis in psychiatric classifications. Our research consists of comparing gaze
      aversion in SAD participants with or without fear of blushing in front of
      pictures of different emotional faces using an eye tracker. Twenty-six
      participants with DSM-IV SAD and expressed fear of blushing (SAD+FB) were
      recruited in addition to twenty-five participants with social phobia and no fear
      of blushing (SAD-FB). Twenty-four healthy participants aged and sex matched
      constituted the control group. We studied the number of fixations and the dwell
      time in the eyes area on the pictures. The results showed gaze avoidance in the
      SAD-FB group when compared to controls and when compared to the SAD+FB group.
      However we found no significant difference between SAD+FB and controls. We also
      observed a correlation between the severity of the phobia and the degree of gaze
      avoidance across groups. These findings seem to support the claim that social
      phobia is a heterogeneous disorder. Further research is advised to decide whether
      fear of blushing can constitute a subtype with specific behavioral
      characteristics.

PMID- 22951334
TI  - Reducing seclusion through involuntary medication: a randomized clinical trial.
AB  - PURPOSE: The study evaluated whether seclusion and coercive incidents would be
      reduced in extent and number if involuntary medication was the first choice of
      intervention. Patients admitted to an acute psychiatric ward were randomly
      allocated to two groups. In Group 1, involuntary medication was the intervention
      of first choice for dealing with agitation and risk of violence. In Group 2,
      seclusion was the intervention of first choice. Patients' characteristics between
      the groups were compared by Pearson chi(2) and two-sample t-tests; the incidence
      rates and risk ratios (RRs) were calculated to examine differences in number and
      duration of coercive incidents. In Group 1, the relative risk of being secluded
      was lower than in Group 2, whereas the risk of receiving involuntary medication
      was higher. However, the mean duration of the seclusion incidents did not differ
      significantly between the two groups; neither did the total number of coercive
      incidents. Although the use of involuntary medication could successfully replace
      and reduce the number of seclusions, alternative interventions are needed to
      reduce the overall number and duration of coercive incidents. A new policy for
      managing acute aggression - such as involuntary medication - can be implemented
      effectively only if certain conditions are met.

PMID- 22951335
TI  - Burnout, compassion fatigue, and compassion satisfaction among staff in community
      based mental health services.
AB  - Providing care to individuals with complex mental health needs can be stressful.
      However, little research has focused on the emotional, cognitive, and physical
      consequences of providing mental health care. The aim of this study is to assess
      burnout (BO), compassion fatigue (CF) and compassion satisfaction (CS) among
      staff at the four community-based mental health services (CMHS) of Verona, Italy.
      All staff were asked to complete anonymously the Professional Quality of Life
      Scale, the General Health Questionnaire, and a socio-demographic questionnaire.
      In total 260 staff participated (a response rate of 84%). Psychiatrists and
      social workers were the professionals with the highest levels of BO and CF.
      Workers with psychological distress reported both higher BO and CF scores, and
      lower levels of CS. A significant increase in the BO and CF scores was also
      detected for each extra year spent working in a CMHS. A higher level of CF was
      associated with female and having been experienced one negative life event in the
      previous year. These findings are useful for health managers and team leaders to
      identify factors affecting the professional quality of life of mental healthcare
      staff, and can provide a rationale for detecting staff at risk for developing
      negative work-related outcomes.

PMID- 22951336
TI  - A cross-cultural replication of an interactive model of anxiety sensitivity
      relevant to suicide.
AB  - Recent findings indicate a relationship between anxiety sensitivity (AS) and
      suicide in a variety of populations in the United States. However, the link
      between AS and suicide has not been evaluated in other cultures. Suicide rates in
      Russia are among the highest worldwide making it an excellent choice to evaluate
      the cross-cultural robustness of these findings. The current investigation sought
      to replicate and extend the investigation of AS subfactors (i.e., cognitive,
      physical, and their interaction) in relation to suicidality in a sample of
      Russian adults. Participants were 390 adults recruited from Moscow using a
      geographic sampling method. Findings from the current study indicate that the
      interaction of AS cognitive concerns and AS physical concerns are associated with
      elevated rates of suicidality and previous suicide attempt, above and beyond
      negative affectivity and hazardous alcohol use. Clinicians may benefit from
      implementing AS reduction strategies with individuals who endorse elevated
      suicide risk as well as elevated AS cognitive concerns and low AS physical
      concerns.

PMID- 22951337
TI  - Which came first, delusions or hallucinations? An exploration of clinical
      differences among patients with first-episode psychosis based on patterns of
      emergence of positive symptoms.
AB  - Remarkably little is known about patterns of emergence of specific symptoms in
      the early course of nonaffective psychotic disorders. Some 159 well-characterized
      first-episode psychosis patients were categorized into those with: (1) delusions
      only (n=29, 18.2%); (2) delusions that emerged at least 1 month before
      hallucinations (n=31, 19.5%); (3) hallucinations that began at least 1 month
      before delusions (n=26, 16.4%); and (4) delusions and hallucinations that emerged
      concomitantly, within the same month (n=73, 45.9%). These four groups were
      compared across a number of clinical features, including duration of untreated
      psychosis, symptom severity, insight, and functioning, while controlling for
      potential confounders. Patients with delusions and hallucinations emerging within
      the same month had a shorter duration of untreated psychosis than those in whom
      one psychotic symptom emerged greater than one month before the other. The
      delusions-only group had significantly less severe positive, negative, and
      general psychopathology symptom scores, as well as better social and occupational
      functioning. Replication and further elucidation of specific patterns of symptom
      emergence would deepen the field's understanding of early-course phenomenology,
      and may inform efforts to improve upon nosology, prognostication, and treatment
      selection.

PMID- 22951338
TI  - Uptake of 17beta-trenbolone and subsequent metabolite trendione by the pinto bean
      plant (Phaseolus vulgaris).
AB  - Manure from livestock feeding operations is commonly applied to agricultural
      fields as an alternative to commercial fertilizers. Trenbolone acetate (TbA) is a
      synthetic growth promoter frequently utilized in beef cattle feeding operations.
      Metabolites of TbA can be present in manure and subsequently applied to fields.
      Fate ofTbA metabolites 17beta-trenbolone (17betaTb), 17alpha-trenbolone
      (17alphaTb), and trendione (TbO) have been assessed in manure and soils, but
      plant uptake in agricultural fields is not fully understood. The objective of
      this study was to investigate potential plant uptake and biotransformation of
      17betaTb using the pinto bean plant (Phaseolus vulgaris). Vegetated (n=20) and
      control sands (n=16) were amended with 17betaTb at a level of 1MUg/g once per
      week for a total of four weeks. Sand, above-ground plant portion and below-ground
      plant portion were collected each week and then analyzed for 17betaTb, 17alphaTb,
      and TbO. By week four, low concentrations of 17betaTb (10+/-4.9MUg/g fresh
      weight) were taken up into the roots of plants and, to a much lesser extent,
      translocated throughout the plant (0.04+/-0.02MUg/g fresh weight). Extensive
      transformation of 17betaTb to the metabolite trendione (TbO) occurred in
      vegetated sand, while minimal TbO was detected in control sand. These results
      suggest the biotransformation of 17betaTb to TbO is predominantly through
      microbial degradation. Trenbolone (Tb) metabolites can then be taken up into
      plants but remain concentrated in the roots with only slight translocation to
      above ground portions of the plant. After four weeks, maximum observed
      concentrations of total Tb (parent+metabolites) in fresh plant tissues were
      33.0MUg/g in roots and 0.25MUg/g in leaves. No phytotoxicity was observed to
      pinto bean plants throughout the four week study.

PMID- 22951340
TI  - T1 radiculopathy.
AB  - The patient was a 40-year-old man who had experienced a constant deep ache over
      his left T1-2 paravertebral muscle region. Following 2 weeks of physical
      therapist intervention with no improvement, the patient self-referred to a
      neurosurgeon. Magnetic resonance imaging of the cervical and upper thoracic spine
      regions was ordered and revealed a left paracentral disc protrusion at T1-2 that
      resulted in moderate left foraminal stenosis.

PMID- 22951339
TI  - 12- and 15-lipoxygenases in adipose tissue inflammation.
AB  - The lipoxygenases (LOs) are principal enzymes involved in the oxidative
      metabolism of polyunsaturated fatty acids, including arachidonic acid. 12- and 15
      LO and their lipid metabolites have been implicated in the development of insulin
      resistance and diabetes. Adipose tissue, and in particular visceral adipose
      tissue, plays a primary role in the development of the inflammation seen in these
      conditions. 12- and 15-LO and their lipid metabolites act as upstream regulators
      of many of the cytokines involved in the inflammatory response in adipose tissue.
      While the role that 12- and 15-LO play in chronically inflamed adipose tissue is
      becoming clearer, there are still many questions that remain unanswered regarding
      their activation, signaling pathways, and roles in healthy fat. 12- and 15-LO
      also generate products with anti-inflammatory properties that are under
      investigation. Therefore, 12- and 15-LO have the potential to be very important
      targets for therapeutics aimed at reducing insulin resistance and the comorbid
      conditions associated with obesity. 

PMID- 22951341
TI  - Mechanical input restrains PPARgamma2 expression and action to preserve
      mesenchymal stem cell multipotentiality.
AB  - Exercise-generated signals are pro-osteogenic and anti-adipogenic within the
      marrow. In vitro studies indicate that mechanical signals directly block
      adipogenic differentiation through activation of beta-catenin and by limiting
      PPARgamma2 expression. Whether mechanically generated beta-catenin can inhibit
      adipogenesis during PPARgamma transactivation is unknown. We evaluated the
      ability of mechanical signals to limit adipogenesis in marrow derived mesenchymal
      stem cells (mdMSC) distal to activation of PPARgamma. First, we established that
      mdMSC attained an adipogenic phenotype within 2-4 days in the presence of
      rosiglitazone (1-25 MUM) and that beta-catenin activation via GSK3beta inhibition
      interfered with this process. Similarly, mechanical strain (3600 cycles, 2%
      strain daily) inhibited adipogenesis at 3 days, preventing rosiglitazone-induced
      PPARgamma upregulation as well as aP2 and adiponectin protein expression. To
      assess whether a reduction in PPARgamma expression was necessary for anti
      adipogenic action, PPARgamma2 was overexpressed: both mechanical strain and
      GSK3beta inhibition prevented expression of aP2 and adiponectin proteins despite
      abundant PPARgamma2 and its ligand. To understand the fate of single cells
      experiencing mechanical strain we generated mdMSC from aP2-GFP reporter
      expressing mice. Rosiglitazone treatment for 3 days induced GFP expression in
      more than 80% of cells. Sorting by GFP expression revealed that the highest 20%
      of aP2-GFP expressing cells was responsible for the majority of adipogenic
      protein expression. This highly expressing GFP fraction had a reduced ability to
      respond to an osteogenic stimulus: BMP-2 treatment increased osterix by 12-fold
      in contrast to the 42-fold increase in osterix expression that resulted from BMP
      2 treatment of the bottom 75% of GFP expressing cells. This suggested that highly
      expressing aP2-GFP cells represented more terminally differentiated adipocytes,
      with reduced multipotentiality. Application of mechanical strain to aP2-GFP mdMSC
      treated with rosiglitazone caused a two-fold decrease in the size of the upper
      cell fraction, suggesting that mechanical strain preserved MSC in a multipotent
      state. Our data show that mechanical strain restricts adipogenesis both by
      limiting PPARgamma2 expression and by preventing PPARgamma action, protecting the
      potential of MSC to enter other lineages.

PMID- 22951342
TI  - Prediction of welfare outcomes for broiler chickens using Bayesian regression on
      continuous optical flow data.
AB  - Currently, assessment of broiler (meat) chicken welfare relies largely on labour
      intensive or post-mortem measures of welfare. We here describe a method for
      continuously and robustly monitoring the welfare of living birds while husbandry
      changes are still possible. We detail the application of Bayesian modelling to
      motion data derived from the output of cameras placed in commercial broiler
      houses. We show that the forecasts produced by the model can be used to
      accurately assess certain key aspects of the future health and welfare of a
      flock. The difference between healthy flocks and less-healthy ones becomes
      predictable days or even weeks before clinical symptoms become apparent. Hockburn
      (damaged leg skin, usually only seen in birds of two weeks or older) can be well
      predicted in flocks of only 1-2 days of age, using this approach. Our model
      combines optical flow descriptors of bird motion with robust multivariate
      forecasting and provides a sparse, efficient model with sparsity-inducing priors
      to achieve maximum predictive power with the minimum number of key variables.

PMID- 22951343
TI  - Repelled from the wound, or randomly dispersed? Reverse migration behaviour of
      neutrophils characterized by dynamic modelling.
AB  - Following neutralization of infectious threats, neutrophils must be removed from
      inflammatory sites for normal tissue function to be restored. Recently, a new
      paradigm has emerged, in which viable neutrophils migrate away from inflammatory
      sites by a process best described as reverse migration. It has generally been
      assumed that this process is the mirror image of chemotaxis, where neutrophils
      are drawn into the areas of infection or tissue damage by gradients of
      chemotactic cues. Indeed, efforts are underway to identify cues that drive
      neutrophils away by the reverse process, fugetaxis. By using photoconvertible
      pigments expressed in neutrophils in transparent zebrafish larvae, we were able
      to image the position of each neutrophil during inflammation resolution in vivo.
      These neutrophil coordinates were analysed within a dynamic modelling framework,
      using different forms of the drift-diffusion equation with model selection and
      parameter estimation based on approximate Bayesian computation. This analysis
      revealed the experimental data were best fitted by a model incorporating a
      diffusion term but no drift term-where the presence of drift would indicate
      fugetaxis. This result, for the first time, provides rigorous data-driven
      evidence that reverse migration of neutrophils in vivo is not a form of
      fugetaxis, but rather a stochastic redistribution.

PMID- 22951344
TI  - Frigatebird behaviour at the ocean-atmosphere interface: integrating animal
      behaviour with multi-satellite data.
AB  - Marine top predators such as seabirds are useful indicators of the integrated
      response of the marine ecosystem to environmental variability at different
      scales. Large-scale physical gradients constrain seabird habitat. Birds however
      respond behaviourally to physical heterogeneity at much smaller scales. Here, we
      use, for the first time, three-dimensional GPS tracking of a seabird, the great
      frigatebird (Fregata minor), in the Mozambique Channel. These data, which provide
      at the same time high-resolution vertical and horizontal positions, allow us to
      relate the behaviour of frigatebirds to the physical environment at the (sub
      )mesoscale (10-100 km, days-weeks). Behavioural patterns are classified based on
      the birds' vertical displacement (e.g. fast/slow ascents and descents), and are
      overlaid on maps of physical properties of the ocean-atmosphere interface,
      obtained by a nonlinear analysis of multi-satellite data. We find that
      frigatebirds modify their behaviours concurrently to transport and thermal
      fronts. Our results suggest that the birds' co-occurrence with these structures
      is a consequence of their search not only for food (preferentially searched over
      thermal fronts) but also for upward vertical wind. This is also supported by
      their relationship with mesoscale patterns of wind divergence. Our multi
      disciplinary method can be applied to forthcoming high-resolution animal tracking
      data, and aims to provide a mechanistic understanding of animals' habitat choice
      and of marine ecosystem responses to environmental change.

PMID- 22951345
TI  - Effect of fresh human amniotic membrane dressing on graft take in patients with
      chronic burn wounds compared with conventional methods.
AB  - BACKGROUND: Burns are among the most devastating forms of injury. Nowadays the
      standard treatment for deep partial thickness and full-thickness burn is early
      excision and grafting, but this technique is not always feasible; and this leads
      to chronicity and microbial colonization of burn wounds. Interesting properties
      of human amniotic membrane made us use it in management of chronic infected burn
      wounds. METHODS: From January 2008 to September 2010, in a prospective clinical
      trail, 38 patients (76 limbs) with symmetric chronic burn wounds in both upper or
      lower limbs included in this study. Tissue cultures were taken from all the
      wounds. For the right, after debridement of granulation tissue and meshed split
      thickness skin grafting, the graft surfaces were covered with amniotic membrane
      dressing and in left limb wounds, after debridement, skin grafting was done in
      conventional method. 21 days later, the success rate of graft take was compared
      between two groups. RESULTS: The study group was composed of 76 limbs in 38
      patients with mean age of 27.18+/-6.38 and burn in 29.18+/-7.23 TBSA%. The most
      common causes of the burn wounds chronicity in the selected patients was delayed
      admission due to poor compliance of the patients (44.8%). Staphylococcus was the
      most frequent isolate in wounds in our patients (62.85%). Mean graft take was
      observed in 90.13% of right upper limbs, and 67.36% of left upper limbs; which
      was significantly different (P<0.001). CONCLUSIONS: Our study showed that human
      amniotic membrane dressing significantly increases the success rate of graft take
      in chronic wounds, and it can be recommended as an important dressing in chronic
      burn wounds management, due to interesting anti-microbial, and better graft take
      effects.

PMID- 22951346
TI  - Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System.
      Part 4: Eight-day randomized clinical trial in Korea.
AB  - A randomized, controlled, open-label parallel-group, single-center study to
      determine biomarkers of exposure to 12 selected harmful and potentially harmful
      constituents (HPHC) in cigarette smoke and urinary excretion of mutagenic
      material in 72 male and female Korean subjects smoking Lark One cigarettes (1.0mg
      tar, 0.1mg nicotine, and 1.5mg CO) at baseline. Subjects were randomized to
      continue smoking Lark One cigarettes, or switch to an Electrically Heated
      Cigarette Smoking System (EHCSS) and EHCSS-K3 cigarette (3mg tar, 0.2mg nicotine,
      and 0.6 mg CO), or to no-smoking. The mean decreases from baseline to Day 8 were
      statistically significant (all p<0.05) for 10 of 12 HPHC in mainstream cigarette
      smoke including CO (the primary objective) in the EHCSS-K3 group (range: -1.5% to
      -74.2%). Exposure to the other determined HPHC was not significantly different.
      In the Lark One group, the mean exposure to 6 of 12 HPHC in cigarette smoke was
      significantly (all p<0.05) decreased; however, exposure to CO was significantly
      increased. The largest mean reductions in biomarkers of exposure to HPHC occurred
      in smokers who switched to no-smoking (-3.4% to -98.9%). The mean excretion of
      mutagenic material was significantly decreased (p<0.05) in the EHCSS-K3 and no
      smoking groups (-31.8% and -45.3%, respectively), and increased in the Lark One
      group (+31.5%).

PMID- 22951347
TI  - Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System.
      Part 6: 6-Day randomized clinical trial of a menthol cigarette in Japan.
AB  - A randomized, controlled, open-label, parallel-group, single-center study to
      determine biomarkers of exposure to 12 selected harmful and potentially harmful
      constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine,
      and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese
      subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4J(M); 4 mg tar
      and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking
      M4J(M), or switch to smoking either the Electrically Heated Cigarette Smoking
      System menthol cigarette (EHCSS-K6(M); 5mg tar and 0.3mg nicotine) or the Lark
      One menthol cigarette (Lark1(M); 1mg tar and 0.1mg nicotine), or to no-smoking.
      The mean decreases from baseline to Day 5/6 were statistically significant (p <=
      0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary
      endpoint (carbon monoxide) and urinary excretion of mutagenic material in the
      EHCSS-K6(M) group (-12.3% to -83.4%). Smaller, but statistically significant
      reductions (p <= 0.05) occurred in the Lark1(M) group (-3.3% to -35.2%), with the
      exception of urinary mutagens. The largest mean reductions (all p <= 0.05) in
      exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in
      the no-smoking group (-1.4% to -93.6%). Serum CC16, an indicator of lung
      epithelial injury, was not significantly different between groups.

PMID- 22951348
TI  - Nanoparticle iron medicinal products - Requirements for approval of intended
      copies of non-biological complex drugs (NBCD) and the importance of clinical
      comparative studies.
AB  - Currently, most countries apply the standard generic approach for the approval of
      intended copies of originator nanoparticle iron medicinal products, requiring
      only demonstration of bioequivalence to a reference medicinal product by
      bioavailability studies. However, growing evidence suggests that this regulatory
      approach is not appropriate. Clinical and non-clinical studies have shown that
      intended copy preparations of nanoparticle iron medicinal products can differ
      substantially from the originator product in their efficacy and potentially in
      their safety profile. An adapted regulatory pathway (separate from the standard
      generic approach) with defined data requirements is needed for approval of
      intended copies of iron medicinal products. Here, we discuss the difficulties
      involved in assessing therapeutic equivalence of nanoparticle iron medicinal
      products and suggest key concepts of a regulatory approach. Standardized non
      clinical comparative studies are necessary but, as demonstrated in the reported
      clinical data, they may not be sufficient to demonstrate a comparable efficacy
      and safety profile. Validated, prospective, comparative clinical studies might be
      needed, in addition to non-clinical studies, in order to enable appropriate
      assessment of therapeutic equivalence. Furthermore, including brand names in
      addition to the International Non-proprietary Names (INNs) in safety reports
      could enable effective safety monitoring of intended copies and originator
      products.

PMID- 22951349
TI  - Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System.
      Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland.
AB  - This randomized, open-label, ambulatory, controlled clinical study investigated
      biomarkers associated with cardiovascular risk and biomarkers of exposure to 10
      selected harmful and potentially harmful constituents (HPHC) in cigarette smoke
      in 316 male and female Polish smokers. Subjects were randomized to continue
      smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically
      Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker
      assessments were performed at several time points during the study at baseline
      and during the 1-month investigational period. The primary biomarkers were high
      sensitivity C-reactive protein and white blood cell counts. No statistically
      significant differences in the two primary biomarkers were found between the
      study groups at the end of the study. End-of-study comparisons of secondary
      biomarkers between study groups indicated an increase in high-density lipoprotein
      cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit
      levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC
      were decreased in the EHCSS-K6 group, despite an increase in cigarette
      consumption, compared to the CC group. There were no apparent differences in any
      of the safety assessment parameters between the groups, and the overall incidence
      of study-related adverse events was low.

PMID- 22951351
TI  - Nav1.5 sodium channels in macrophages in multiple sclerosis lesions.
AB  - BACKGROUND: Macrophages are dynamic participants in destruction of white matter
      in active multiple sclerosis (MS) plaques. Regulation of phagocytosis and myelin
      degradation along endosomal pathways in macrophages is highly-orchestrated and
      critically-dependent upon acidification of endosomal lumena. Evidence from in
      vitro studies with macrophages and THP-1 cells suggests that sodium channel
      Nav1.5 is present in the limiting membrane of maturing endosomes where it plays a
      prominent role in the accumulation of protons. However, a contribution of the
      Nav1.5 channel to macrophage-mediated events in vivo has not been demonstrated.
      METHOD: We examined macrophages within active MS lesions by immunohistochemistry
      to determine whether Nav1.5 is expressed in these cells in situ and, if
      expressed, whether it is localized to specific compartments along the endocytic
      pathway. RESULTS: Our results demonstrate that Nav1.5 is expressed within
      macrophages in active MS lesions, and that it is preferentially expressed in late
      endosomes and phagolysosomes (Rab7(+), LAMP-1(+)), and sparsely expressed in
      early (EEA-1(+)) endosomes. Triple-immunolabeling studies showed localization of
      Nav1.5 within Rab7(+) endosomes containing proteolipid protein, a myelin marker,
      in macrophages within active MS plaques. CONCLUSIONS: These observations support
      the suggestion that Nav1.5 contributes to the phagocytic pathway of myelin
      degradation in macrophages in vivo within MS lesions.

PMID- 22951350
TI  - In-bore setup and software for 3T MRI-guided transperineal prostate biopsy.
AB  - MRI-guided prostate biopsy in conventional closed-bore scanners requires
      transferring the patient outside the bore during needle insertion due to the
      constrained in-bore space, causing a safety hazard and limiting image feedback.
      To address this issue, we present our custom-made in-bore setup and software to
      support MRI-guided transperineal prostate biopsy in a wide-bore 3 T MRI scanner.
      The setup consists of a specially designed tabletop and a needle-guiding template
      with a Z-frame that gives a physician access to the perineum of the patient at
      the imaging position and allows the physician to perform MRI-guided transperineal
      biopsy without moving the patient out of the scanner. The software and Z-frame
      allow registration of the template, target planning and biopsy guidance.
      Initially, we performed phantom experiments to assess the accuracy of template
      registration and needle placement in a controlled environment. Subsequently, we
      embarked on our clinical trial (N = 10). The phantom experiments showed that the
      translational errors of the template registration along the right-left (RP) and
      anterior-posterior (AP) axes were 1.1 +/- 0.8 and 1.4 +/- 1.1 mm, respectively,
      while the rotational errors around the RL, AP and superior-inferior axes were
      (0.8 +/- 1.0) degrees , (1.7 +/- 1.6) degrees  and (0.0 +/- 0.0) degrees ,
      respectively. The 2D root-mean-square (RMS) needle-placement error was 3 mm. The
      clinical biopsy procedures were safely carried out in all ten clinical cases with
      a needle-placement error of 5.4 mm (2D RMS). In conclusion, transperineal
      prostate biopsy in a wide-bore 3T scanner is feasible using our custom-made
      tabletop setup and software, which supports manual needle placement without
      moving the patient out of the magnet.

PMID- 22951352
TI  - Breastfeeding is associated with lower risk for multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease with known genetic
      and environmental susceptibility factors. Breastfeeding has been shown to be
      protective in other autoimmune diseases. OBJECTIVE: This case-control study
      analyzed the association of breastfeeding in infancy on the risk of developing
      MS. METHODS: A case-control study was performed in Berlin of 245 MS patients and
      296 population-based controls, who completed a standardized questionnaire on
      their history and duration of breastfeeding in infancy and demographic
      characteristics. Univariable and multivariable logistic regression analysis was
      performed to investigate the association between breastfeeding and MS. The
      multivariate model was adjusted for age, gender, number of older siblings, number
      of inhabitants in place of domicile between ages 0 and 6 (categorized in each
      case), and daycare attendance between ages 0 and 3. RESULTS: In multivariable
      analysis, breastfeeding showed an independent association with MS (adjusted OR
      0.58; p = 0.028). However, with no breastfeeding as reference, the protective
      effect only emerges after four months of breastfeeding (multivariable analysis
      for <= four months adjusted OR 0.87; p = 0.614 and for > four months OR 0.51; p =
      0.016). CONCLUSION: The results of this case-control study support the hypothesis
      that breastfeeding is associated with a lower risk of MS. These results are in
      line with findings of previous studies on other autoimmune diseases, in which
      breastfeeding was shown to have protective effects.

PMID- 22951354
TI  - Src kinases are important regulators of mitochondrial functions.
AB  - Mitochondria produce the most part of the energy used by the cells. This
      energetic production occurs through the oxidative phosphorylation (OXPHOS)
      process. Mitochondrial functions such as OXPHOS need to be tightly regulated to
      respect the needs of cells. Phosphorylation of mitochondrial proteins now appears
      as a major regulation pathway of mitochondrial functions. Several kinases and
      phosphatases are specifically targeted to mitochondria where they modulate
      mitochondrial functions. However, we still poorly understand the extent of
      tyrosine phosphorylation events on mitochondrial metabolism. Among the tyrosine
      kinases observed in mitochondria, Src kinases emerge as key players. In the past
      years, several mitochondrial proteins were shown to be substrates of Src kinases.
      Notably, these kinases can impact greatly OXPHOS and apoptosis. Important
      regulators of Src kinases activity are also observed in mitochondria. The aim of
      this review is to summarize the recent findings on how overall mitochondrial
      tyrosine phosphorylation events and more specifically Src kinases can influence
      mitochondrial functions. The different mechanisms of Src kinases regulation and
      translocation into mitochondria will be also discussed. This article is part of a
      Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

PMID- 22951353
TI  - HIV infection and obesity: where did all the wasting go?
AB  - BACKGROUND: The success of antiretroviral therapy (ART) has led to dramatic
      changes in causes of morbidity and mortality in HIV-infected individuals. As
      chronic diseases rates have increased in HIV+ populations, modifiable risk
      factors such as obesity have increased in importance. Our objective was to
      evaluate factors associated with weight change among patients receiving ART.
      METHODS: ART-naive patients initiating therapy at the University of Alabama -
      Birmingham 1917 HIV/AIDS Clinic from 2000- 2008 were included. Body Mass Index
      (BMI) was categorized as: underweight (<18.5), normal weight (18.5-24.9),
      overweight (25-29.9) and obese (>=30). Linear regression models were used to
      evaluate overall change in BMI and factors associated with increased BMI category
      24 months following ART initiation. RESULTS: Among 681 patients, the mean
      baseline BMI was 25.4 +/- 6.1; 44% of patients were overweight/obese. At 24
      months, 20% of patients moved from normal to overweight/obese or overweight to
      obese BMI categories. Greater increases in BMI were observed in patients with
      baseline CD4 count < 50 cells/ul (3.4 +/- 4.1, P<0.01) and boosted protease
      inhibitor use (2.5+/-4.1 P=0.01), but did not account for all of the variation
      observed in weight change. CONCLUSIONS: The findings that almost half of patients
      were overweight or obese at ART initiation, and 1 in 5 patients moved to a
      deleterious BMI category within 2 years of ART initiation are alarming. ART
      therapy provides only a modest contribution to weight gain in patients. Obesity
      represents a highly prevalent condition in patients with HIV infection and an
      important target for intervention.

PMID- 22951356
TI  - Influence of soil copper content on the kinetics of thiram adsorption and on
      thiram leachability from soils.
AB  - This work aimed to assess the influence of soil copper content on the sorption
      processes of thiram, a fungicide widely used in agriculture, most of the times
      together with copper. Two different types of studies were performed: (1)
      desorption studies of thiram with acetonitrile after batch adsorption
      equilibration, and ageing of the wet soil for a variable period of time; (2)
      kinetic studies of thiram adsorption performed using the soil in its original
      form and after fortification with copper ions. In the desorption studies, with
      the increase of the ageing time, a decrease of the thiram peak and a simultaneous
      increase of a new peak, assigned to a copper complex, were observed in the
      chromatograms. This new peak increases sharply until an ageing period of about 4d
      and then this area is maintained approximately constant until 18 d, the maximum
      ageing period studied. These results indicate that thiram reacts with copper ions
      along time giving rise to the formation of relatively persistent copper complexes
      in soil. Desorption studies with CaCl(2) 0.01 M solution showed that this complex
      is not extracted. Thus, it is not easily leached to ground and surface waters and
      copper may contribute to thiram immobilization in soil. The kinetic studies of
      thiram adsorption were performed in both soils and for two initial thiram
      concentrations (~7 and 20 mg L(-1)). For the soil fortified with copper the
      percentage of adsorbed thiram is higher than observed for the original soil at
      the same initial concentrations and equilibration times and 100% of adsorption is
      attained in 15 h or 48 h, depending on the thiram initial concentration. Four
      kinetic equations, the pseudo first- and second-order equations, the Elovich and
      the intraparticle diffusion equations were selected to fit the kinetic data of
      the adsorption process of thiram onto both original and fortified soil. The best
      model to describe the kinetics of thiram adsorption onto the original soil is the
      intraparticle diffusion model. For the soil fortified with copper ions we
      verified that for the highest initial thiram concentration, the best model is
      also the intraparticle diffusion model, however, for the lower initial thiram
      concentration the best model is the pseudo second-order kinetic equation,
      suggesting that, for a high Cu:Thi ratio, a chemical reaction of thiram with
      copper ions on the soil surface can occur, and it may be the rate controlling
      step. Since the kinetics of adsorption depends on both soil copper content and
      the initial thiram concentration in solution, i.e. depends on Cu:Thi ratio, it is
      difficult to choose a fixed batch equilibration time for adsorption studies of
      thiram.

PMID- 22951355
TI  - Contributions of maltreatment and serotonin transporter genotype to depression in
      childhood, adolescence, and early adulthood.
AB  - BACKGROUND: Past findings on gene-by-environment (G*E) effects on depression have
      been mixed, leading to a debate of the plausibility of such mechanisms and
      methodological considerations that warrant attention. A developmental systems
      perspective postulates that complex, multi-level G*E effects are likely
      contributors to depression. METHODS: Participants from families experiencing low
      income status at birth were followed over 28 years. Maltreatment was recorded
      prospectively using multiple means and sources. Depression was measured
      repeatedly using well-validated interviews in middle childhood, through
      adolescence, and into adulthood. RESULTS: Findings support a G*E effect where the
      less efficient form of the promoter region of the serotonin transporter gene (5
      HTTLPR) contributes to a vulnerability to depressogenic aspects of maltreatment
      in childhood and adolescence. The presence of less efficient forms of the 5
      HTTLPR polymorphism and maltreatment together raised risk for depression. This
      G*E effect was present generally and also among those who reported clinical
      levels of depression at only one point in time. LIMITATIONS: This study used a
      low-income sample which limits generalizability to other populations. Sample size
      and rates of different forms of depression and depression at individual
      developmental stages supported general analyses, but limited the sorts of
      specific sub-analyses that were possible. CONCLUSIONS: These findings support the
      plausibility of G*E effects on depression during childhood, adolescence, and
      early adulthood, key periods for the development of depression. Ongoing debates
      about the presence of G*E effects would be well served by additional work that
      was theoretically informed and employed prospective, longitudinal methodologies
      with well-validated measures of key constructs.

PMID- 22951357
TI  - Maternal autism-associated IgG antibodies delay development and produce anxiety
      in a mouse gestational transfer model.
AB  - A murine passive transfer model system was employed to ascertain the effects of
      gestational exposure to a single, intravenous dose of purified, brain-reactive
      IgG antibodies from individual mothers of children with autism (MAU) or mothers
      with typically developing children (MTD). Growth and behavioral outcomes in
      offspring were measured from postnatal days 8 to 65 in each group. Comparisons
      revealed alterations in early growth trajectories, significantly impaired motor
      and sensory development, and increased anxiety. This report demonstrates for the
      first time the effects of a single, low dose gestational exposure of IgG derived
      from individual MAU on their offspring's physical and social development.

PMID- 22951358
TI  - A single center, open, randomized study investigating the clinical safety and the
      endothelial modulating effects of a prostacyclin analog in combination with
      eptifibatide in patients having undergone primary percutaneous coronary
      intervention (PCI) for ST-segment elevation myocardial infarction.
AB  - Treatment with the endothelial modulator prostacyclin may be beneficial in
      patients with endothelial dysfunction. The primary aim of the present pilot study
      was to evaluate the safety and the potential endothelial modulating affect of the
      prostacyclin analog iloprost in patients with a recent ST segment elevation
      myocardial infarction (STEMI). Seventeen patients were randomized to either 24 h
      of iloprost infusion in combination with low dose eptifibatide infusion or saline
      infusion+eptifibatide. The study was randomized and open labeled. None of the
      patients experienced any bleeding complications and vital signs were stable
      throughout the entire study period in both groups. None of the functional
      hemostatic whole blood assays applied in the present study differed between the
      active treatment and the placebo group. The endothelial marker, sE-selectin,
      displayed a decrease over time in the iloprost group but increased in the placebo
      group (p=0.008), whereas none of the other biomarkers of endothelial cell and
      glycocalyx activation or damage differed significantly between the groups. In
      this pilot study, infusion of a prostacyclin analog appeared safe and has a
      detectable modulating effect of activated endothelium in patients with a recent
      STEMI. ClinicalTrials.gov: NCT01179776.

PMID- 22951359
TI  - Temporary percutaneous ileostomy versus conventional loop ileostomy in mechanical
      extraperitoneal colorectal anastomosis: a retrospective study.
AB  - AIM: Loop ileostomy is a suitable procedure for transitory faecal diversion after
      low colorectal anastomosis, but it causes relevant morbidities (discomfort,
      peristomal infections, dehydration) and requires a second operation to be closed.
      We already described an alternative technique of temporary percutaneous ileostomy
      (TPI) that can be removed without surgery. METHOD: The data of 143 consecutive
      patients, undergoing elective laparoscopic anterior resection of the rectum for
      adenocarcinoma and low mechanical colorectal anastomosis, 68 with conventional
      loop ileostomy (CLI) and 75 with TPI, were analyzed. RESULTS: Neither intra
      operative complications nor deaths occurred during the follow-up period. Clinical
      anastomotic leakage occurred in 4 patients with CLI and in 1 with TPI (p =
      0.191). The median time required for the emission of gases and faeces through the
      stoma was respectively 1 and 2.5 days in the CLI group, and 1 and 2 days in the
      TPI group (p = 0.259 and p = 0.126). The median post-operative stay was 8 days in
      the CLI group and 11 days in the TPI group (p < 0.001). PTIs were removed on the
      median of 9 days after surgery without major complications, whereas the CLIs were
      re-canalized in 79.4% of patients on an average of 106 days, with 2 major
      complications. CONCLUSION: The temporary percutaneous ileostomy seems to be a
      valid alternative to conventional ileostomy, ensuring optimal faecal diversion
      and less patient discomfort. It can be easily removed without surgery, allowing
      patients a better outcome.

PMID- 22951360
TI  - The effects of group cycling on gait and pain-related disability in individuals
      with mild-to-moderate knee osteoarthritis: a randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To determine the
      effectiveness of a community-based program of stationary group cycling on gait,
      pain, and physical function in individuals with mild-to-moderate knee
      osteoarthritis (OA). BACKGROUND: Knee pain and disability are common symptoms in
      individuals with knee OA. Though exercise for knee OA has acknowledged benefits,
      it has the potential to aggravate symptoms in some instances. METHODS: Thirty
      seven subjects (27 women, 10 men) with a mean +/- SD age of 57.7 +/- 9.8 years
      were randomly assigned to a cycling (n = 19) or control (n = 18) group for a 12
      week intervention study. Outcome variables, measured at baseline and 12 weeks,
      included preferred and maximal gait velocity, a visual analog pain scale at rest
      and following a 6-minute walk test, muscle strength, and functional-outcome
      questionnaires. Data were analyzed using mixed-model analyses of variance for
      group and time differences. RESULTS: After 12 weeks, the individuals receiving
      the cycling intervention showed significantly greater improvements (P<.05) for
      preferred gait velocity (mean difference between groups, 8.7 cm/s; 95% confidence
      interval [CI]: 2.2, 15.1), visual analog pain scale on the 6-minute walk test
      (mean difference, 16.5 mm; 95% CI: 2.1, 31.0), the Western Ontario and McMaster
      Universities Osteoarthritis Index pain subscale (mean difference, 14.9 points;
      95% CI: 2.6, 27.0) and stiffness subscale (mean difference, 10.8 points; 95% CI:
      0.7, 21.3), the Knee injury and Osteoarthritis Outcome Score pain subscale (mean
      difference, 13.3 points; 95% CI: 3.4, 23.3), and the Knee Outcome Survey
      activities of daily living subscale (mean difference, 13.9 points; 95% CI: 2.0,
      25.9) compared to controls. CONCLUSION: Stationary group cycling may be an
      effective exercise option for individuals with mild-to-moderate knee OA and may
      reduce pain with walking. US trial registration NCT00917618. LEVEL OF EVIDENCE:
      Therapy, level 1b-.

PMID- 22951361
TI  - Regional absolute conductivity reconstruction using projected current density in
      MREIT.
AB  - Magnetic resonance electrical impedance tomography (MREIT) is a non-invasive
      technique for imaging the internal conductivity distribution in tissue within an
      MRI scanner, utilizing the magnetic flux density, which is introduced when a
      current is injected into the tissue from external electrodes. This magnetic flux
      alters the MRI signal, so that appropriate reconstruction can provide a map of
      the additional z-component of the magnetic field (B(z)) as well as the internal
      current density distribution that created it. To extract the internal electrical
      properties of the subject, including the conductivity and/or the current density
      distribution, MREIT techniques use the relationship between the external
      injection current and the z-component of the magnetic flux density B = (B(x),
      B(y), B(z)). The tissue studied typically contains defective regions, regions
      with a low MRI signal and/or low MRI signal-to-noise-ratio, due to the low
      density of nuclear magnetic resonance spins, short T(2) or T*(2) relaxation
      times, as well as regions with very low electrical conductivity, through which
      very little current traverses. These defective regions provide noisy B(z) data,
      which can severely degrade the overall reconstructed conductivity distribution.
      Injecting two independent currents through surface electrodes, this paper
      proposes a new direct method to reconstruct a regional absolute isotropic
      conductivity distribution in a region of interest (ROI) while avoiding the
      defective regions. First, the proposed method reconstructs the contrast of
      conductivity using the transversal J-substitution algorithm, which blocks the
      propagation of severe accumulated noise from the defective region to the ROI.
      Second, the proposed method reconstructs the regional projected current density
      using the relationships between the internal current density, which stems from a
      current injection on the surface, and the measured B(z) data. Combining the
      contrast conductivity distribution in the entire imaging slice and the
      reconstructed regional projected current density, we propose a direct non
      iterative algorithm to reconstruct the absolute conductivity in the ROI. The
      numerical simulations in the presence of various degrees of noise, as well as a
      phantom MRI imaging experiment showed that the proposed method reconstructs the
      regional absolute conductivity in a ROI within a subject including the defective
      regions. In the simulation experiment, the relative L2-mode errors of the
      reconstructed regional and global conductivities were 0.79 and 0.43,
      respectively, using a noise level of 50 db in the defective region.

PMID- 22951362
TI  - Green Brazilian propolis effects on sperm count and epididymis morphology and
      oxidative stress.
AB  - Basal generation of reactive oxygen species (ROS) is essential for male
      reproductive function, whereas high ROS levels may be linked to low quality of
      sperm and male infertility. The number of antioxidants known to inflict damage is
      growing, and it will be of interest to study natural products, which may have
      this activity. Since the epididymis is known to play an important role in
      providing the microenvironment for sperm maturation and storage of sperm, this
      study was undertaken to evaluate the morphometric-stereological and functional
      alterations in the epididymis after chronic treatment with low doses of Brazilian
      green propolis, which is known for its antioxidant properties. For this purpose,
      forty-eight adult male Wistar rats were treated with 3, 6 and 10 mg/kg/day of
      aqueous extract of Brazilian green propolis during 56 days and morphological
      parameters, sperm production and number of sperm in rat epididymis and oxidative
      stress levels were analyzed. The results showed higher sperm production and
      greater epithelium height of the epididymis initial segment and no induction of
      oxidative stress in treated animals. Further studies are needed to fully
      understand the effects of propolis on the reproductive system but our results
      showed that it could alter male reproductive function.

PMID- 22951363
TI  - [Multiple ulcers of the lower limbs].

PMID- 22951364
TI  - A new tool to study ribavirin-induced haemolysis.
AB  - BACKGROUND: Today, treatment of chronic hepatitis C is based on a synergistic
      combination of pegylated interferon and ribavirin with antiprotease inhibitors.
      Haemolytic anaemia, which is the major side effect of ribavirin treatment,
      disrupts ribavirin treatment compliance and varies significantly from one patient
      to another. There is an individual susceptibility to ribavirin haemolysis. With a
      view to studying haemolysis, and thus optimizing the treatment response, we have
      developed a new in vitro tool for analysing the ribavirin-induced lysis of red
      blood cells. METHODS: Resuspended red blood cells were incubated with isotonic
      buffer and a range of concentrations of ribavirin. Haemolysis was quantified by
      spectrophotometric measurement of the supernatant at 540 nm. The assay was used
      to test the effects of various compounds and to investigate the susceptibility of
      patients to haemolytic anaemia. RESULTS: In our assay, the degree of haemolysis
      is dependent on the ribavirin concentration used and can be inhibited by the
      addition of dipyridamole (50% inhibitory concentration [IC(50)] 30 MUM), ATP or
      glutathione (IC(50) 1.63 mM and 767 MUM, respectively). We observed a strong
      decrease in red blood cell haemolysis in the presence of the ribavirin prodrug
      viramidine (Taribavirin((r))). When testing the performance of this assay with
      blood from 24 patients before treatment, we observed a strong correlation between
      in vitro haemolysis before treatment and the decrease in haemoglobin levels seen
      in vivo during subsequent treatment (P<0.001). CONCLUSIONS: With this new tool it
      is possible to better evaluate individual susceptibility to ribavirin-induced
      haemolysis before the start of treatment. In addition, this model will enable the
      mechanism of ribavirin-induced anaemia to be further explored and allow molecules
      that could reduce ribavirin haemolysis to be screened and tested in vitro. This
      approach could help optimize current and future therapeutic strategies involving
      ribavirin in the treatment of chronic hepatitis C.

PMID- 22951365
TI  - Oral delivery of anticancer drugs I: general considerations.
AB  - Historically, most of anticancer drugs were delivered by the intravenous route
      which is the most direct one leading to immediate and complete bioavailability of
      the drugs. However, this administration route could result in several side
      effects and requires a clinic or hospitalization visit, nursing and palliative
      treatment. For these latter reasons, oral delivery of anticancer drugs is
      nowadays more and more considered, including already marketed drugs. In this
      first review, we aim to identify general considerations for the oral delivery of
      anticancer drugs. In the second and the third reviews we respectively discuss the
      prodrug strategy and the use of drug delivery systems to improve the oral
      bioavailability of anticancer drugs.

PMID- 22951366
TI  - Clinical improvement after extracranial venoplasty in multiple sclerosis.
AB  - PURPOSE: This study proposed to prospectively evaluate safety and clinical
      changes in outpatient endovascular treatment in patients with multiple sclerosis
      (MS) and chronic cerebrospinal venous insufficiency (CCSVI). MATERIALS AND
      METHODS: Two hundred fifty-nine patients with MS were followed with the Multiple
      Sclerosis Impact Scale (MSIS-29) before and for 1 and 6 months after treatment of
      extracranial internal jugular vein and azygos vein stenoses and occlusions using
      venous angioplasty, as well as stent placement in 2.5% of patients. Before
      treatment, the patients were tested with magnetic resonance (MR) venography and
      flow quantification. RESULTS: We found statistically significant improvements in
      the MSIS-29 scores (P < .01) at both 1 and 6 months. At 1 and 6 months, 67.9% and
      53.6% were improved on the physical scale, respectively, and 53.0% and 44.4% were
      improved on the psychological scale, respectively. Women showed greater
      improvement than did men on the physical scale at 6 months (P = .01). Patients
      with primary progressive MS (PPMS) showed less improvement than did those with
      relapsing-remitting MS (RRMS) on the psychological scale at 1 month, and
      venoplasty treatment of more vein sites versus fewer vein sites showed greater
      improvement on the physical scale at both 1 and 6 months. Fifteen patients (6.3%)
      reported recurrent symptoms after clinical improvement and were treated again.
      There was one serious adverse event, a deep venous thrombosis at the catheter
      insertion site, which resolved with treatment. CONCLUSIONS: Endovascular
      treatment of CCSVI in patients with MS appears to be a safe procedure resulting
      in significant clinical improvement.

PMID- 22951368
TI  - Cord blood triglycerides are associated with IGF-I levels and contribute to the
      identification of growth-restricted neonates.
AB  - OBJECTIVE: The aim of this study was to investigate whether readily available
      laboratory tests may aid in the identification of growth-restricted neonates.
      DESIGN: Cord serum levels of 15 chemical analytes, including insulin-like growth
      factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) were
      measured in newborns >=36 weeks gestational age (GA). Based on the number of
      anthropometric indices (out of four) with values <=25th centile for GA, the
      babies were allocated into three groups, i.e., Group(25)0, Group(25)1 and
      Group(25)2 corresponding to neonates with 0, 1 and 2 or more indices,
      respectively, that were <=25th centile for GA. Furthermore, two composite
      variables were developed: A25 (Group(25)0 and Group(25)1) and B25 (Group(25)0 and
      Group(25)2). The data were evaluated by the Mann-Whitney test and multiple
      regression analyses. RESULTS: Cord serum triglycerides and total cholesterol
      levels were significantly higher in Group(25)2 compared to Group(25)0 (p values
      0.004 and 0.0009, respectively). The triglycerides almost doubled the power of
      the variable B25 for predicting IGF-I levels and were found to have a highly
      significant, negative association with the IGF-I levels (p<0.0001). The IGF-I
      along with the IGFBP-3 levels explained almost one third of the variation of
      triglycerides. CONCLUSION: Cord serum triglycerides can assist in the
      identification of growth-restricted neonates. The novel finding of the
      association of triglycerides with IGF-I calls for further research as this can
      illuminate unknown aspects of the fetal lipid metabolism.

PMID- 22951367
TI  - ATP is released from autophagic vesicles to the extracellular space in a VAMP7
      dependent manner.
AB  - Autophagy is a normal degradative pathway that involves the sequestration of
      cytoplasmic components and organelles in a vacuole called autophagosome. SNAREs
      proteins are key molecules of the vesicle fusion machinery. Our results indicate
      that in a mammalian tumor cell line a subset of VAMP7 (V-SNARE)-positive vacuoles
      colocalize with LC3 at the cell periphery (focal adhesions) upon starvation. The
      re-distribution of VAMP7 positive structures is a microtubule-dependent event,
      with the participation of the motor protein KIF5 and the RAB7 effector RILP.
      Interestingly, most of the VAMP7-labeled vesicles were loaded with ATP. Moreover,
      in cells subjected to starvation, these structures fuse with the plasma membrane
      to release the nucleotide to the extracellular medium. Summarizing, our results
      show the molecular components involved in the release of ATP to extracellular
      space, which is recognized as an important autocrine/paracrine signal molecule
      that participates in the regulation of several cellular functions such as
      immunogenicity of cancer cell death or inflammation.

PMID- 22951369
TI  - DFNB35 due to a novel mutation in the ESRRB gene in a Czech consanguineous
      family.
AB  - OBJECTIVES: Non-syndromic hearing loss (NSHL) is a genetically heterogeneous
      disorder with mostly autosomal recessive inheritance. So far 40 genes and the
      same amount of loci with as yet unknown genes were described with autosomal
      recessive NSHL. PATIENTS AND METHODS: A consanguineous Czech family with a child
      with NSHL was genotyped using SNP array and homozygous regions were compared with
      previously reported DFNB loci. RESULTS: GRXCR1 and ESRRB genes associated with
      autosomal recessive NSHL were located in two of the eight homozygous regions
      detected by SNP array genotyping. Mutation p.R291L in a homozygous state was
      found in the deaf child, the parents were heterozygous. The entire coding region
      of the ESRRB gene was sequenced in additional 39 patients of Czech origin with
      early NSHL and only two variants, p.V413I and p.P386S, were found in homozygous
      state, but are considered to be polymorphisms. CONCLUSION: Homozygosity mapping
      is a powerful method for identification of genes in heterogeneous recessive
      diseases. This is the first report of DFNB35 mutations in the Czech Republic and
      it seems to be a rare cause of NSHL. Additional mutations in ESRRB gene were
      reported in Pakistan, Tunisia and Turkey.

PMID- 22951370
TI  - Anterior cruciate ligament reconstruction in skeletally immature patients with
      transphyseal tunnels.
AB  - PURPOSE: Our purpose was to evaluate the results of transphyseal anterior
      cruciate ligament (ACL) reconstruction with hamstring autograft in skeletally
      immature patients. METHODS: Eighteen knees in 18 skeletally immature pubescent
      patients with a mean chronologic age of 14.2 years underwent transphyseal ACL
      reconstruction with hamstring autograft between 2002 and 2007. Concurrent
      meniscal surgery was performed in 9 knees. The final patient evaluation occurred
      at a mean of 43.4 months (range, 24.0 to 86.6 months) and included physical
      examination, KT-1000 arthrometry testing (MEDmetric, San Diego, CA), and
      functional outcome instruments, including the International Knee Documentation
      Committee subjective knee form, the Lysholm knee score, and the Tegner knee
      activity scale. RESULTS: At the latest follow-up, the mean International Knee
      Documentation Committee subjective knee score was 92.4 +/- 10, the mean Lysholm
      knee score was 94.3 +/- 8.8, and the mean Tegner activity scale score was 8.5 +/-
      1.4. Lachman and pivot-shift testing were negative in all knees. No restriction
      in knee range of motion of 5 degrees  or greater when compared with the
      contralateral knee was observed in any patient. The mean manual maximum side-to
      side difference with KT-1000 testing was 0.29 +/- 1.07 mm, and no patients had a
      difference greater than 3 mm. No angular deformities were noted, and all leg
      length measurements were symmetric bilaterally on clinical examination. No
      patients had traumatic graft disruption or underwent revision ACL reconstruction,
      whereas 3 patients sustained an ACL injury in the contralateral leg while
      participating in sports. CONCLUSIONS: Transphyseal ACL reconstruction with
      autogenous quadrupled hamstring graft with metaphyseal fixation in skeletally
      immature pubescent patients yielded excellent functional outcomes in a high
      percentage of patients without perceived clinical growth disturbance. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 22951371
TI  - Single- and double-bundle anterior cruciate ligament reconstruction in patients
      aged over 50 years.
AB  - PURPOSE: The purpose of our study was to retrospectively evaluate the outcomes
      after anterior cruciate ligament (ACL) reconstruction with hamstring in patients
      aged 50 years or older. In addition, we present, for the first time, the outcomes
      of a subgroup of middle-aged patients treated with double-bundle (DB)
      reconstruction. METHODS: Fifty patients aged 50 years or older underwent primary
      ACL reconstruction with hamstring. Inclusion criteria were primary ACL
      reconstruction in active patients. Exclusion criteria were multiligamentous
      injuries and a contralateral ACL-deficient knee. The mean age at surgery was 54.4
      years (range, 50 to 65 years). The mean period from the initial injury to surgery
      was 32.6 months (range, 3 to 125 months). Of the patients, 36 underwent single
      bundle (SB) ACL reconstruction and 14 underwent DB reconstruction. Patients were
      assessed preoperatively with physical examination (including range of motion,
      pivot-shift test, and instrumented knee laxity measurement), the Lysholm score,
      the International Knee Documentation Committee scoring system, and the Tegner
      activity scale. Standard radiographs were taken, and degenerative changes were
      graded according to the Ahlback radiologic classification of arthritis. RESULTS:
      Patients were evaluated at a mean of 4.4 years (range, 2 to 7 years) after
      surgery. A significant improvement in knee function and symptoms was reported in
      most patients, with increased Lysholm, International Knee Documentation
      Committee, and Tegner scores (P < .001). The outcomes of clinical assessment and
      instrumented laxity testing were clearly improved when compared with preoperative
      status (P < .001). The level of osteoarthritis did not statistically increase at
      follow-up. No statistically significant difference could be observed between the
      SB and DB groups (P = not significant). CONCLUSIONS: Operative treatment showed
      favorable outcomes in most of the ACL-reconstructed patients with regard to knee
      stability, osteoarthritis progression, and patient satisfaction in a cohort of
      subjects aged 50 years or older. Our subgroup of patients undergoing DB ACL
      reconstruction reported average satisfactory outcomes, which did not
      significantly differ from the SB group. LEVEL OF EVIDENCE: Level IV, therapeutic
      case series.

PMID- 22951372
TI  - Pathomorphologic findings of wrist arthroscopy in children and adolescents with
      chronic wrist pain.
AB  - PURPOSE: The purposes of this diagnostic study were to show pathomorphologic
      findings of children and adolescents with persistent wrist pain and to compare
      these arthroscopic findings with preoperative magnetic resonance imaging (MRI).
      METHODS: A total of 41 arthroscopies in 39 patients were retrospectively
      reviewed. The patients underwent diagnostic wrist arthroscopy because of
      persistent wrist pain after at least 3 months of unsuccessful conservative
      treatment. Of the patients, 22 (56.4%) reported an injury before the onset of
      pain. The mean age at arthroscopy was 15.3 years (range, 9.8 to 19.4 years), and
      the mean duration between the onset of symptoms and arthroscopic exploration was
      19.9 months (range, 3.0 to 121.0 months). RESULTS: Among all affected wrists, 33
      (80.5%) showed a triangular fibrocartilage complex (TFCC) tear on arthroscopy,
      with 75.6% also showing other pathomorphologic findings. Retrospectively, the
      condition of the TFCC was correctly identified by MRI in only 17 wrists (41.5%).
      In contrast, 23 wrists were incorrectly classified as having "no tear" whereas
      arthroscopy later indeed showed a TFCC tear. Concerning the TFCC, MRI and
      arthroscopy showed a significant difference of outcome (P < .01), indicating low
      agreement (kappa = 0.09) for the outcome of the 2 methods. A larger proportion of
      TFCC tears was found for patients with injuries (91.3%) as compared with the
      other patients (66.7%), although this was not significant on statistical analysis
      (P = .11). No significant difference in the time to surgery was found between
      patients with TFCC tears and those without TFCC tears classified by MRI (P = .76)
      and by arthroscopy (P = .99). CONCLUSIONS: Wrist arthroscopy in children and
      adolescents with chronic wrist pain shows TFCC lesions in a high percentage.
      However, most of these lesions have not been correctly identified by MRI before
      arthroscopy. Thus diagnostic wrist arthroscopy may be recommended to rule out
      underlying pathologies and initiate further therapeutic steps. LEVEL OF EVIDENCE:
      Level III, diagnostic study of nonconsecutive patients.

PMID- 22951373
TI  - Tibialis anterior or posterior allograft anterior cruciate ligament
      reconstruction versus hamstring autograft reconstruction: an economic analysis in
      a hospital-based outpatient setting.
AB  - PURPOSE: To analyze and compare the direct costs, reimbursement rates, gross
      contribution margins, and operating room and recovery room times for anterior
      cruciate ligament (ACL) reconstructions with the use of soft-tissue allografts
      and autografts. We aimed to determine the financial impact of using allograft
      tissue for ACL reconstruction in a hospital-based outpatient setting. METHODS:
      Financial data from the facility billing database and operating room (OR) reports
      from the electronic medical record were queried to identify all patients
      undergoing arthroscopic ACL reconstruction during a 12-month period. A subset of
      patients who had isolated ACL reconstruction with or without simple meniscectomy
      or chondral debridement was identified as the study group. We compared 46 ACL
      reconstructions using tibialis anterior or posterior allografts and 50 ACL
      reconstructions using hamstring autografts. Facility direct cost, reimbursement
      rates, gross contribution margin, OR times, and other variables were compared.
      RESULTS: The facility mean direct cost for ACL reconstruction using allografts
      was $4,587, with a mean OR time of 92 minutes. The mean direct cost and OR time
      for ACL reconstruction using autografts were $3,849 and 125 minutes,
      respectively. Allograft ACL reconstructions were $738 more costly, and
      reimbursement was also higher. Allograft ACL reconstruction produced a 41.5%
      margin with a gross contribution margin of $3,248, whereas autografts had a
      reimbursement rate with a 45% margin with a gross contribution margin of $3,156.
      CONCLUSIONS: In this study the cost of allograft tissue used in ACL
      reconstruction was not offset by the savings realized from shorter OR and
      recovery room times. However, in a hospital-based outpatient setting,
      reimbursement covered the cost of the allograft, offsetting the additional
      expense. LEVEL OF EVIDENCE: Level III, retrospective comparative study for
      economic analysis.

PMID- 22951374
TI  - Compulsive use of alcohol among college students.
AB  - Among college students alcohol consumption is associated with other high-risk
      behaviors that can lead to short- and long-term negative health consequences.
      Identification of college students consuming alcohol who are at high risk for
      problems may have important public health implications. This study examines the
      ability of the CHQ compulsive use of alcohol item to detect high-risk behaviors
      relative to other screening measures and its association with different
      dimensions of compulsive drinking. Three hundred thirty-two college students
      completed measures on compulsive drinking and hazardous behaviors. Results showed
      that among male students the CHQ compulsive use of alcohol item was not sensitive
      to detect hazardous alcohol consumption but co-occurred with the use of illicit
      drugs. Among female students it was sensitive to detect heavy drinking but not
      alcohol or drug problems. Among college students compulsive use of alcohol
      corresponds to an urge to consume alcohol that may be associated with use of
      illicit drugs in male students, with heavy drinking in female students and with
      substance use problems. This study suggest that the CHQ compulsive use of alcohol
      item should not be used as a stand-alone screening for alcohol or drug problems
      but it could be considered a marker for at-risk behaviors.

PMID- 22951375
TI  - Epilepsy surgery in a developing  country (Lebanon):  ten years experience  and
      predictors of outcome.
AB  - We present our 10-year experience and preoperative predictors of outcome in 93
      adults and children who underwent epilepsy surgery at the American University of
      Beirut. Presurgical evaluation included video-EEG monitoring, MRI,
      neuropsychological assessment with invasive monitoring, and other tests (PET,
      SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and
      multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%),
      and corpus callosotomy (1%). Mesial temporal sclerosis was the most common
      aetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14%
      class III, and 7% class IV. The number of antiepileptic drugs before surgery was
      the only preoperative factor associated with Engel class I (p=0.005). Despite the
      presence of financial and philanthropic aid, many patients could not be operated
      on for financial reasons. We conclude that advanced epilepsy presurgical workups,
      surgical procedures, and favourable outcomes, comparable to those of developed
      countries, are achievable in developing countries, but that issues of financial
      coverage remain to be addressed.

PMID- 22951376
TI  - Neandertal mobility and large-game hunting: the exploitation of reindeer during
      the Quina Mousterian at Chez-Pinaud Jonzac (Charente-Maritime, France).
AB  - Neandertals were effective hunters of large ungulates throughout their geographic
      and temporal ranges. Equipped with this knowledge, researchers in
      paleoanthropology continue to seek insight on the relationships between hunting
      and subsistence strategies with other components of the Neandertals' niche, such
      as mobility, site use, and lithic technology. The Quina Mousterian deposits from
      the rockshelter site of Chez Pinaud Jonzac (Charente-Maritime, France; hereafter
      Jonzac) offer an excellent opportunity to pursue these issues. This paper focuses
      on the extensive and well-preserved skeletal remains of reindeer (Rangifer
      tarandus) recovered from recent excavations of the site, representing at least 18
      individuals that were hunted by Neandertals during the fall through winter. Our
      zooarchaeological results indicate that all ages of reindeer were hunted but
      adult individuals predominate. No bias is evident in the comparable frequencies
      of males and females. These prey were butchered on-site, with abundant evidence
      of meat filleting and marrow exploitation. In the excavated sample, the absence
      of hearths and the almost complete lack of burned bones or stones suggest that
      Neandertals were not using fire to assist with processing the reindeer carcasses.
      The zooarchaeological results presented here indicate that reindeer were hunted
      during a restricted window of time when they were seasonally abundant in the
      local area near Jonzac. Taken together with the lithic industry based on bifacial
      elements, the evidence is consistent with a pattern of site use by highly mobile
      hunter-gatherers making frequent, short-term visits. Ongoing research at Jonzac
      and other Quina Mousterian localities will contribute to a better understanding
      of Neandertal behavior during cold climate phases.

PMID- 22951377
TI  - Electromechanical delay of the vastus medialis obliquus and vastus lateralis in
      individuals with patellofemoral pain syndrome.
AB  - STUDY DESIGN: Case-control study. OBJECTIVE: To examine electromechanical delay
      (EMD) of the vastus medialis obliquus (VMO) and the vastus lateralis (VL) in
      individuals with patellofemoral pain syndrome (PFPS). BACKGROUND: EMD is a
      mechanical property of muscles related to protective reflex and sports
      performance. The time duration of the EMD can be shortened with strength training
      and, conversely, can be lengthened secondary to immobilization. However, it is
      unclear if EMD between various components of the quadriceps is affected in
      individuals with PFPS. METHODS: Twenty-six individuals with PFPS and 26 healthy
      volunteers were studied. The VMO and VL were electrically stimulated to evoke
      muscle twitches. Ultrasound was used to assess patellar movement elicited by the
      muscle twitch. The time from the onset of electrical stimulation to the onset of
      patellar movement was measured as the EMD. The EMDs of the VMO and VL were
      compared between groups using a mixed-model analysis of variance. RESULTS:
      Subsequent to a significant interaction (P<.001), post hoc analysis indicated
      that the EMD of the VMO was longer (PFPS, 37.3 +/- 0.7 milliseconds; control,
      25.9 +/- 0.7 milliseconds; P<.001) and the EMD of the VL was shorter (PFPS, 18.4
      +/- 0.5 milliseconds; control, 25.1 +/- 0.5 milliseconds; P<.001) in the PFPS
      group. Therefore, in the individuals with PFPS, the EMD of the VMO was
      significantly longer than that of the VL (P<.001), which was not the case for
      those in the control group (P = .20). CONCLUSION: The mechanical properties of
      the VMO and VL may be altered in patients with PFPS.J Orthop Sports Phys Ther
      2012;42(9):791-796, Epub 2 August 2012. doi:10.2519/jospt.2012.3973.

PMID- 22951378
TI  - Mechanisms of high-dose citalopram-induced death in a rat model.
AB  - Citalopram, a selective serotonin reuptake inhibitor, is generally considered to
      be of low toxicity. However, serotonin syndrome, seizures, electrocardiographic
      abnormalities as well as respiratory failure and death have been described in
      patients with citalopram overdose. The mechanisms of severe toxicity remain
      unclear. Our objective was to study the mechanisms of death following high-dose
      citalopram administration in Sprague Dawley rats. The median lethal dose (MLD) of
      intraperitoneal (i.p.) citalopram was measured using Dixon & Bruce's up-and-down
      method at 102 mg/kg. Dose-effect relationships of citalopram-induced clinical
      features, alterations in arterial blood gas and plethysmography, and disturbances
      in blood lactate, plasma and platelet serotonin concentrations were studied.
      Seizures were significantly increased in rats receiving 80% and 120% of
      citalopram MLD versus controls (p<0.05 and p<0.01, respectively). A significant
      decrease in body temperature was observed after 90 min in rats treated with doses
      >60% MLD in comparison to controls (p<0.05). The occurrence of serotonin
      behavioural syndrome was comparable in all groups. Citalopram administration did
      not result in significant hypoxemia, hypercapnia and lactate elevation. However,
      a significant moderate increase in the inspiratory time (p<0.05) accompanied with
      an expiratory braking was observed. A significant dose-related linear decrease in
      platelet serotonin and increase in plasma serotonin concentrations were measured
      (p<0.05). Pre-treatments of rats receiving 120% of citalopram MLD with diazepam
      (1.77 mg/kg) and cyproheptadine (17.1mg/kg) prevented seizures and death, but
      propranolol pre-treatment was ineffective. Neuroprotection with diazepam and
      cyproheptadine was not associated with decreased serotonin plasma concentrations.
      In conclusion, citalopram-induced deaths resulted from seizures in relation to
      serotonin release, whilst respiratory and metabolic toxicity was mild. Our
      observations support the role of serotonin-induced neurotoxicity in citalopram
      overdose and suggest that cyproheptadine and benzodiazepines, but not beta
      blockers, may have a role in the management of citalopram toxicity.

PMID- 22951379
TI  - Identification of scuticociliates (Pseudocohnilembus persalinus, P. longisetus,
      Uronema marinum and Miamiensis avidus) based on the cox1 sequence.
AB  - Scuticociliatosis is characterized as highly histophagous, causing systemic
      tissue destruction and high mortality in cultured marine fish. Some of the
      scuticociliates have been implicated as the causative agents of
      scuticociliatosis. Here, we describe our study to differentially identify various
      species in complex animal-sourced samples, namely olive flounder Paralichthys
      olivaceus and black rockfish Sebastes schlegelii suffering from
      scuticociliatosis. The mitochondrial cytochrome c oxidase 1 (cox1) gene from the
      scuticociliates was amplified and sequenced. The divergence percentage of small
      subunit ribosomal DNA sequence between average scuticociliate species was found
      to be low (8.3%) but the genetic divergence of cox1 sequence reached 23.5%,
      suggesting that a hyper-variable region of the cox1 gene could be used as a
      diagnostic DNA barcoding region. Thus, we developed species-specific primers for
      use in multiplex PCR of complex (pooled) samples. The primers yielded species
      specific fragments (of distinct size) that allowed for simple, rapid, and
      effective identification and differentiation of multiple species present in a
      single sample.

PMID- 22951380
TI  - Cortisol awakening response in infants during the first six postnatal months and
      its relation to birth outcome.
AB  - CONTEXT: The rise of cortisol concentrations after awakening is well documented
      in adults and children and commonly used as easily accessible marker of
      hypothalamic-pituitary-adrenal (HPA) reactivity. OBJECTIVE: The purpose of this
      study was to demonstrate the existence of a salivary cortisol awakening response
      (CAR) in infants, and to estimate its association with birth outcome. SETTING:
      The study was conducted in the general community. PARTICIPANTS: Healthy infants
      up to six months age (N=64). MAIN OUTCOME MEASURES: Mothers were instructed to
      collect their infant's saliva immediately and 30 min after awakening on two days
      within 45 days, irrespective of awakening time. Information on birth outcome was
      collected from medical records and questionnaires. RESULTS: Linear mixed models
      analysis revealed a significant rise of infant salivary cortisol concentrations
      within 30 min after awakening (b=0.128, SE=0.024, t61=5.31, p<0.001), which was
      quite stable across the two sampling days (r=0.40, p=0.002). The infant CAR was
      predicted by length of gestation (t58=2.44, p=0.018). CONCLUSIONS: The current
      data demonstrate the existence of a CAR in infants as early as during the first
      six postnatal months; its relationship with length of gestation supports its
      usefulness for questions related to developmental neuroscience. Therefore, the
      infant CAR emerges as non-invasive biomarker of HPA axis dynamics at this early
      stage of life, with relevance for future research and potential clinical
      applications.

PMID- 22951381
TI  - Optimal partial-arcs in VMAT treatment planning.
AB  - We present a method for improving the delivery efficiency of VMAT by extending
      the recently published VMAT treatment planning algorithm vmerge to automatically
      generate optimal partial-arc plans. A high-quality initial plan is created by
      solving a convex multicriteria optimization problem using 180 equi-spaced beams.
      This initial plan is used to form a set of dose constraints, and a set of partial
      arc plans is created by searching the space of all possible partial-arc plans
      that satisfy these constraints. For each partial-arc, an iterative fluence map
      merging and sequencing algorithm (vmerge) is used to improve the delivery
      efficiency. Merging continues as long as the dose quality is maintained above a
      user-defined threshold. The final plan is selected as the partial-arc with the
      lowest treatment time. The complete algorithm is called pmerge. Partial-arc plans
      are created using pmerge for a lung, liver and prostate case, with final
      treatment times of 127, 245 and 147 . Treatment times using full arcs with vmerge
      are 211, 357 and 178 s. The mean doses to the critical structures for the vmerge
      and pmerge plans are kept within 5% of those in the initial plan, and the target
      volume covered by the prescription isodose is maintained above 98% for the pmerge
      and vmerge plans. Additionally, we find that the angular distribution of fluence
      in the initial plans is predictive of the start and end angles of the optimal
      partial-arc. We conclude that VMAT delivery efficiency can be improved by
      employing partial-arcs without compromising dose quality, and that partial-arcs
      are most applicable to cases with non-centralized targets.

PMID- 22951382
TI  - Diplopia, driving and DVLA.

PMID- 22951384
TI  - Odds ratio of risk factors for oral submucous fibrosis in a case control model.
AB  - Our aim was to calculate the odds ratio (OR) of various epidemiological, social,
      behavioural, and dietary risk factors for oral submucous fibrosis in a population
      based case control study. We did this in rural and urban Lucknow by organising
      oral health camps in the community, where a total of 3136 subjects were enrolled.
      Panmasala, a dry commercial preparation containing areca nut, slaked lime,
      catechu, and condiments, with or without tobacco, was the most important
      aetiological factor for the disease. The 95% confidence interval (CI) of the OR
      for tobaccoless panmasala ranged from 4.77 to 6.88 and for tobacco panmasala from
      4.55 to 9.71. OR using multivariate analysis was 14.09 for tobaccoless panmasala
      and 5.39 for tobacco panmasala. Patients who use panmasala are at high risk of
      developing oral submucous fibrosis. 

PMID- 22951383
TI  - In vivo evaluation of titanium-prepared platelet-rich fibrin (T-PRF): a new
      platelet concentrate.
AB  - We have developed a new, titanium-prepared, platelet-rich fibrin (T-PRF) together
      with the protocol for forming it, which is based on the hypothesis that titanium
      tubes may be more effective at activating platelets than the glass tubes used by
      Chouckroun in his platelet-rich fibrin (PRF) method. The aim of this study was to
      find a suitable animal model in which to evaluate the method and to investigate
      the efficacy of T-PRF for wound healing. Blood samples from 6 rabbits were used
      to confirm the protocol for formation of T-PRF. We evaluated T-PRF or T-PRF-like
      clots morphologically using scanning electron microscopy (EM). Blood samples from
      5 rabbits were used to develop an experiment in which to evaluate the effects of
      T-PRF on wound healing. The mucoperiosteal flaps were filled with autologous T
      PRF membranes from the vestibule in the anterior mandibular regions. Samples
      collected from the surgical sites were stained with haematoxylin and eosin. We
      found a mature fibrin network in T-PRF clots that had been centrifuged for 15 min
      at 3500 rpm and, 15 days after placement of the membrane, we found newly-forming
      connective tissue and islets of bony tissue in the T-PRF membrane. These results
      show that T-PRF could induce the formation of new bone with new connective tissue
      in a rabbit model of wound healing within 30 days of treatment.

PMID- 22951386
TI  - Emerging role of epigenetics and miRNA in diabetic cardiomyopathy.
AB  - The prevalence of heart failure independent of coronary artery disease and
      hypertension is increasing rapidly in diabetic patients. Thus, this
      pathophysiology has been recognized as a distinct clinical entity termed
      "diabetic cardiomyopathy." Several studies support the notion that diabetes is a
      threatening insult for the myocardium resulting in functional, cellular, and
      structural changes manifesting as a cardiac myopathy. Recent data suggested that
      epigenetics including DNA and histone modifications as well as microRNAs play an
      important role in the development of cardiac diseases. The role of epigenetics in
      diabetes is largely recognized; however, its role in diabetes-associated
      cardiomyopathy remains elusive. Thus, molecular, cellular, and functional
      modulations in the diabetic cardiomyopathy will be investigated in this review.
      Moreover, particular attention will be drawn on the epigenetic mechanisms that
      may play an important role in the pathophysiology of diabetic cardiomyopathy.

PMID- 22951385
TI  - GB virus C infection is associated with a reduced rate of reactivation of latent
      HIV and protection against activation-induced T-cell death.
AB  - BACKGROUND: GB virus C (GBV-C) coinfection is associated with reduced immune
      activation and a block in CD4(+) T-cell proliferation following interleukin-2 (IL
      2) therapy in HIV-infected individuals. We examined peripheral blood mononuclear
      cells (PBMCs) from HIV-infected subjects with and without GBV-C viraemia to
      determine if GBV-C correlated with reactivation of latent HIV, T-cell
      proliferation or T-cell survival following in vitro activation with
      phytohaemagglutinin A and IL-2 (PHA/IL-2). METHODS: HIV-infected subjects whose
      HIV viral load was suppressed on combination antiretroviral therapy (cART) for >6
      months were studied. PBMCs were cultured with and without PHA/IL-2 and monitored
      for HIV reactivation, proliferation and survival. GBV-C viraemia and in vitro
      replication were detected by real-time RT-PCR. HIV reactivation was determined by
      measuring HIV p24 antigen in culture supernatants. Proliferation was measured by
      counting viable cells and survival measured by flow cytometry. RESULTS: Of 49 HIV
      infected individuals, 26 had GBV-C viraemia. Significantly less HIV reactivation
      and PBMC proliferation following in vitro activation with PHA/IL-2 was observed
      in samples from GBV-C viraemic subjects compared with non-viraemic controls.
      Following 5 weeks in culture, GBV-C replication was associated with preservation
      of CD4(+) and CD8(+) T-cells compared with non-viraemic controls. CONCLUSIONS:
      GBV-C appears to inhibit immune activation and IL-2 signalling pathways, which
      might contribute to a reduction in reactivation of latent HIV from cellular
      reservoirs. In addition, GBV-C viraemia was associated with a reduction in
      activation-induced T-cell death. GBV-C-associated T-cell effects could contribute
      to the observed protective effect of GBV-C coinfection in HIV-infected
      individuals.

PMID- 22951387
TI  - Cardiac teratogenicity in mouse maternal phenylketonuria: defining phenotype
      parameters and genetic background influences.
AB  - Maternal phenylketonuria (MPKU) is a syndrome including cardiovascular
      malformations (CVMs), microcephaly, intellectual impairment, and small size for
      gestational age, caused by in-utero exposure to elevated serum phenylalanine
      (Phe) due to PKU in the mother. It is becoming a public health concern as more
      women with PKU reach child bearing age. Although a mouse model of PKU, BTBR
      Pah(enu2), has been available for 20 years, it has not been well utilized for
      studying MPKU. We used this model to delineate critical parameters in Phe
      cardiovascular teratogenicity and study the effect of genetic background. Dosing
      and timing experiments were performed with the BTBR Pah(enu2) mouse. A dose
      response curve was noted, with CVM rates at maternal serum Phe levels <360 MUM
      (control), 360-600 MUM (low), 600-900 MUM (mid), and >900 MUM (high) of 11.86%,
      16.67%, 30.86%, and 46.67% respectively. A variety of CVMs were noted on the BTBR
      background, including double outlet right ventricle (DORV), aortic arch artery
      (AAA) abnormalities, and ventricular septal defects (VSDs). Timed exposure
      experiments identified a teratogenic window from embryonic day 8.5-13.5, with
      higher rates of conotruncal and valve defects occurring in early exposure time
      and persistent truncus arteriosus (PTA) and aortic arch branching abnormalities
      occurring with late exposure. Compared to the BTBR strain, N10+ Pah(enu2)
      congenics on the C3H/HeJ background had higher rates of CVMs in general and
      propensity to left ventricular outflow tract (LVOT) malformations, while the
      C57B/L6 background had similar CVM rates but predominately AAA abnormalities. We
      have delineated key parameters of Phe cardiovascular teratogenicity, demonstrated
      the utility of this MPKU model on different mouse strains, and shown how genetic
      background profoundly affects the phenotype.

PMID- 22951388
TI  - Methionine adenosyltransferase I/III deficiency: neurological manifestations and
      relevance of S-adenosylmethionine.
AB  - Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations
      in the MAT1A gene, is an inherited metabolic disorder characterized by persistent
      hypermethioninemia, usually detected by newborn mass screening. There is a wide
      range of clinical manifestations, from completely asymptomatic to neurological
      problems associated with brain demyelination. Physiological role of S
      adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT,
      in the central nervous system has been investigated in vivo and in vitro, and
      case reports demonstrated an effectiveness of supplementary treatment of SAM in
      the improvement of neurological development and myelination. Methionine
      restriction can be an additional therapeutic strategy because hypermethioninemia
      alone may be neurotoxic; however, lowering methionine carries a risk to decrease
      the synthesis of SAM.

PMID- 22951389
TI  - Chemical composition, antioxidant and antibacterial activities of the leaf
      essential oil of Juglans regia L. and its constituents.
AB  - The essential oil from the leaves of Juglans regia L. (Juglandaceae) growing wild
      in Kashmir (India) was obtained by hydrodistillation and analysed by a
      combination of capillary GC-FID and GC-MS. A total of 38 compounds, representing
      92.7% of the oil, were identified and the major components were found to be alpha
      pinene (15.1%), beta-pinene (30.5%), beta-caryophyllene (15.5%) germacrene D
      (14.4%) and limonene (3.6%). The essential oil and the main individual
      constituents were screened for antibacterial activity and the essential oil
      evaluated for antioxidant activity. Antibacterial activity was evaluated using
      the disc diffusion and microdilution methods against a group of clinically
      significant Gram-positive (Staphylococcus epidermidis MTCC-435, Bacillus subtilis
      MTCC-441, Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris
      MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella
      dyssenteriae, Klebsiella pneumonia and Escherichia coli). The essential oil and
      its major components exhibited broad spectrum inhibition against all the
      bacterial strains with Gram-positive being more susceptible to the oil than Gram
      negative bacteria. Antioxidant activity of the oil was evaluated by the
      scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals.
      In general, the essential oil exhibited high antioxidant activity which was
      comparable to the reference standards at the same dose (ascorbic acid and
      butylated hydroxyl toluene, BHT) with IC(50) values of 34.5 and 56.4MUg/ml
      calculated by DPPH and hydroxyl radical scavenging assays respectively.

PMID- 22951390
TI  - Cerebroprotective effect of Eclipta alba against global model of cerebral
      ischemia induced oxidative stress in rats.
AB  - Oxidative stress is believed to contribute to neuronal damage induced by cerebral
      ischemia/reperfusion (I/R) injury. The present study was undertaken to evaluate
      the possible cerebroprotective and antioxidant effect of hydroalcoholic extract
      of Eclipta alba against global cerebral ischemia in the rat. Adult Wistar albino
      rats were treated with extract of Eclipta alba (250 and 500mg/kg/day, p.o.) for
      10 days. The global cerebral ischemia-reperfusion injury was induced by occluding
      bilateral common carotid arteries (BCCA) for 30min, followed by 4h reperfusion.
      Quercetin (20mg/kg, i.p.) was used for the reference compound. After that,
      animals were sacrificed by decapitation, brain was removed, various biochemical
      estimations, cerebral edema, assessment of cerebral infarct size, and
      histopathological examinations were carried out. BCCA caused significant
      depletion in superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced
      glutathione (GSH), catalase (CAT), glutahione-S-transferase (GST), glutathione
      ruductase (GR) and significant increase in malondialdehyde (MDA) in brain.
      Pretreatment with hydroalcoholic extract of Eclipta alba significantly reversed
      the levels of biochemical parameters and significantly reduced the edema and
      cerebral infarct size as compared to the ischemic control group. Eclipta alba at
      higher dose markedly reduced ischemia-induced neuronal loss of the brain.
      Reduction of cerebral edema, an early symptom of ischemia, is one of the most
      important remedies for reducing subsequent chronic neural damage in stroke. The
      results of the study show that Eclipta alba pretreatment ameliorates cerebral
      ischemia/reperfusion injury and enhances the antioxidant defense against BCCA
      occlusion induced I/R in rats; so it exhibits cerebroprotective property. HPLC
      fingerprint of hydroalcoholic extract of Eclipta alba was performed for
      conforming the coumestan present in the plant extract.

PMID- 22951391
TI  - EGb 761 promotes osteoblastogenesis, lowers bone marrow adipogenesis and
      atherosclerotic plaque formation.
AB  - AIM OF THE STUDY: Our earlier study has demonstrated that EGb 761 (standardized
      extract of Ginkgo) has the bone sparing effect on the estrogen deficiency induced
      bone loss model. In the present study, we have addressed the question whether
      treatment of osteoporosis benefits arterial calcification or vice versa, because
      both adipocyte and osteoblast originate from the same mesenchymal cell of the
      bone marrow cell (BMC) population. MATERIALS AND METHODS: Bone marrow cells were
      isolated to study the effect of EGb 761 on osteoblast and adipocytes. For in vivo
      effect hamsters were fed high fat diet and the effect of EGb 761 studied on
      atherosclerotic plaque formation and endothelial function. RESULTS: BMC's
      undergoing induced osteogenic or adipogenic differentiations in the presence of
      EGb 761 show increase and decrease in mineralization and adipogenesis
      respectively. Osteogenic and adipogenic mRNAs, reveal lineage dependent
      expression patterns. Runx-2 (osteoblast transcription factor) showed a
      progressive increase, whereas PPAR-gamma (adipogenic regulator) was attenuated,
      with same pattern of expression being for late osteogenic and adipogenic genes.
      EGb 761 led to increase in apoptotic cells and ROS, an important upstream signal.
      In vivo experiments in hamsters after induction with high cholesterol diet (HCD)
      show improvement in endothelial function by EGb 761 with lowering in total plasma
      cholesterol levels. EGb 761 led to vascular preservation of the aortic lumen with
      impairment of the endothelium dependent relaxation which was corroborated by
      micro-CT and histological sections of the thoracic region of the aorta.
      CONCLUSION: From this data, it can be implied that EGb 761 controls bone loss,
      adiposity and lowers atherogenic risk factor after HCD induction.

PMID- 22951392
TI  - Upregulation of osteoblastic differentiation marker mRNA expression in osteoblast
      like UMR106 cells by puerarin and phytoestrogens from Pueraria mirifica.
AB  - Phytoestrogens have attracted attention for their potential in the prevention of
      postmenopausal osteoporosis. Recently, phytoestrogen-rich herb Pueraria mirifica
      has been demonstrated to possess an osteogenic effect on bone in ovariectomized
      rats, but its underlying cellular mechanism was not known. Here, we investigated
      the effects of P. mirifica extract and its major isoflavone compound, puerarin,
      on cell viability, cell proliferation and the expression of differentiation
      markers in rat osteoblast-like UMR106 cells. After exposure to 17beta-estradiol
      (E2), genistein, P. mirifica extract and puerarin, proliferation but not
      viability of UMR106 cells was markedly decreased. Quantitative real-time PCR
      revealed that P. mirifica extract and puerarin significantly increased the mRNA
      expression of alkaline phosphatase (ALP) and osteoprotegerin, but not Runx2,
      osterix or osteocalcin. Puerarin also decreased the mRNA expression of receptor
      activator of nuclear factor-kappaB ligand, an osteoclastogenic factor, suggesting
      that it could induce bone gain by enhancing osteoblast differentiation and
      suppressing osteoclast function. Furthermore, after an exposure to high affinity
      estrogen receptor (ER) antagonist (ICI182780), the E2-, genistein-, P. mirifica
      extract- and puerarin-induced upregulation of ALP expressions were completely
      abolished. It could be concluded that P. mirifica extract and puerarin induced
      osteoblast differentiation rather than osteoblast proliferation in an ER
      dependent manner. The present findings, therefore, corroborated the potential
      benefit of P. mirifica extract and puerarin in the prevention and treatment of
      postmenopausal osteoporosis.

PMID- 22951393
TI  - Marchantin A, a macrocyclic bisbibenzyl ether, isolated from the liverwort
      Marchantia polymorpha, inhibits protozoal growth in vitro.
AB  - In vitro anti-plasmodial activity-guided fractionation of a diethyl ether extract
      of the liverwort species Marchantia polymorpha, collected in Iceland, led to
      isolation of the bisbibenzyl ether, marchantin A. The structure of marchantin A
      (1) was confirmed by NMR and HREIMS. Marchantin A inhibited proliferation of the
      Plasmodium falciparum strains, NF54 (IC(50)=3.41MUM) and K1 (IC(50)=2.02MUM) and
      showed activity against other protozoan species Trypanosoma brucei rhodesiense,
      T. cruzi and Leishmania donovani with IC(50) values 2.09, 14.90 and 1.59MUM,
      respectively. Marchantin A was tested against three recombinant enzymes (PfFabI,
      PfFabG and PfFabZ) of the PfFAS-II pathway of P. falciparum for malaria
      prophylactic potential and showed moderate inhibitory activity against PfFabZ
      (IC(50)=18.18MUM). In addition the cytotoxic effect of marchantin A was
      evaluated. This is the first report describing the inhibitory effects of the
      liverwort metabolite marchantin A against these parasites in vitro.

PMID- 22951394
TI  - Antimicrobial and anti-biofilm properties of new taxodione derivative from hairy
      roots of Salvia austriaca.
AB  - The aim of the present report was to evaluate antimicrobial/anti-biofilm activity
      of 7-(2-oxohexyl)-taxodione, a novel taxodione derivative isolated from n-hexane
      extract of Salvia austriaca hairy roots. Antimicrobial assays showed that 7-(2
      oxohexyl)-taxodione was at least 4 times more active than taxodione against
      methicillin-susceptible as well against methicillin-resistant staphylococci with
      MIC of 1.25-2.5 MUgml(-1). This compound was less active against vancomycin
      resistant enterococci (VRE), on the same level as taxodione (MIC ranged 10.0-20.0
      MUgml(-1)). The presence of 7-(2-oxohexyl)-taxodione in the culture medium (at
      MIC, 1/2 MIC or 1/4 MIC) decreased adhesion of staphylococci to abiotic surfaces,
      which in turn caused a reduction in biofilm formation during 24h, by
      approximately 25-30%. Also, the extent of established biofilm eradication was
      found to be significant, although it required an increased concentration of the
      compound. This is the first report on the antimicrobial activity of this, up to
      now not known compound, isolated from transformed roots of S. austriaca.

PMID- 22951395
TI  - Extraction of volatile oil from aromatic plants with supercritical carbon
      dioxide: experiments and modeling.
AB  - An overview of the studies carried out in our laboratories on supercritical fluid
      extraction (SFE) of volatile oils from seven aromatic plants: pennyroyal (Mentha
      pulegium L.), fennel seeds (Foeniculum vulgare Mill.), coriander (Coriandrum
      sativum L.), savory (Satureja fruticosa Beguinot), winter savory (Satureja
      montana L.), cotton lavender (Santolina chamaecyparisus) and thyme (Thymus
      vulgaris), is presented. A flow apparatus with a 1 L extractor and two 0.27 L
      separators was built to perform studies at temperatures ranging from 298 to 353 K
      and pressures up to 30.0 MPa. The best compromise between yield and composition
      compared with hydrodistillation (HD) was achieved selecting the optimum
      experimental conditions of extraction and fractionation. The major differences
      between HD and SFE oils is the presence of a small percentage of cuticular waxes
      and the relative amount of thymoquinone, an oxygenated monoterpene with important
      biological properties, which is present in the oils from thyme and winter savory.
      On the other hand, the modeling of our data on supercritical extraction of
      volatile oil from pennyroyal is discussed using Sovova's models. These models
      have been applied successfully to the other volatile oil extractions.
      Furthermore, other experimental studies involving supercritical CO(2) carried out
      in our laboratories are also mentioned.

PMID- 22951396
TI  - Effects of velvet antler with blood on bone in ovariectomized rats.
AB  - In traditional Chinese medicine (TCM), both velvet antlers (VA) and VA blood can
      tonify qi, essence, and marrow, nourish the blood, and invigorate bones and
      tendons. In TCM, the combination of VA and VA blood is believed to have superior
      pharmacological effects. Scientific evidence supporting the traditional
      therapeutic preference for redder antler is needed. The effectiveness of the
      combination therapy of VA middle sections (VAMs) and VA blood (VAM-B) was first
      examined in promoting proliferation of mouse osteoblastic cells (MC3T3-E1). The
      anti-osteoporotic activity of VAM-B (ratio of VAM:VA blood = 1:0.2) was evaluated
      with ovariectomized (OVX) rats at a dose of 0.2 g/kg. In VAM-B-treated OVX rats,
      the body weight decreased 10.7%, and the strength of vertebrae and the femur
      respectively increased 18.1% and 15.4%, compared to the control. VAM-B treatment
      also recovered the estrogen-related loss of the right tibial trabecular bone
      microarchitecture. Alkaline phosphatase (ALP) significantly decreased, but
      estradiol did not significantly change in serum of VAM-B-treated OVX rats. We
      also provide an effective strategy to enhance the anti-osteoporotic activity of
      VAM. In conclusion, our results provide scientific evidence supporting the
      traditional therapeutic preference of redder antler and indicate that VAM-B is a
      potential therapeutic agent for managing osteoporosis.

PMID- 22951397
TI  - Specific binding of anionic porphyrin and phthalocyanine to the G-quadruplex with
      a variety of in vitro and in vivo applications.
AB  - The G-quadruplex, a four-stranded DNA structure with stacked guanine tetrads (G
      quartets), has recently been attracting attention because of its critical roles
      in vitro and in vivo. In particular, the G-quadruplex functions as ligands for
      metal ions and aptamers for various molecules. Interestingly, the G-quadruplex
      can show peroxidase-like activity with an anionic porphyrin, iron (III)
      protoporphyrin IX (hemin). Importantly, hemin binds to G-quadruplexes with high
      selectivity over single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA),
      which is attributable to an electrostatic repulsion of phosphate groups in ssDNA
      and dsDNA. The G-quadruplex and hemin-G-quadruplex complex allow development of
      sensing techniques to detect DNA, metal ions and proteins. In addition to hemin,
      anionic phthalocyanines also bind to the G-quadruplex formed by human telomere
      DNA, specifically over ssDNA and dsDNA. Since the binding of anionic
      phthalocyanines to the G-quadruplex causes an inhibition of telomerase activity,
      which plays a role in the immortal growth of cancer cells, anionic
      phthalocyanines are promising as novel anticancer drug candidates. This review
      focuses on the specific binding of hemin and anionic phthalocyanines to G
      quadruplexes and the applications in vitro and in vivo of this binding property.

PMID- 22951398
TI  - Triple subcellular targeting of isopentenyl diphosphate isomerases encoded by a
      single gene.
AB  - Isopentenyl diphosphate isomerase (IDI) is a key enzyme of the isoprenoid
      pathway, catalyzing the interconversion of isopentenyl diphosphate and
      dimethylallyl diphosphate, the universal precursors of all isoprenoids. In
      plants, several subcellular compartments, including cytosol/ER, peroxisomes,
      mitochondria and plastids, are involved in isoprenoid biosynthesis. Here, we
      report on the unique triple targeting of two Catharanthus roseus IDI isoforms
      encoded by a single gene (CrIDI1). The triple localization of CrIDI1 in
      mitochondria, plastids and peroxisomes is explained by alternative transcription
      initiation of CrIDI1, by the specificity of a bifunctional N-terminal
      mitochondria/plastid transit peptide and by the presence of a C-terminal
      peroxisomal targeting signal. Moreover, bimolecular fluorescence complementation
      assays revealed self-interactions suggesting that the IDI likely acts as a
      multimer in vivo.

PMID- 22951399
TI  - Identification of two-component system elements downstream of AHK5 in the
      stomatal closure response of Arabidopsis thaliana.
AB  - To optimize water use efficiency, plants regulate stomatal closure through a
      complex signaling process. Hydrogen peroxide (H2O2) is produced in response to
      several environmental stimuli, and has been identified as a key second messenger
      involved in the regulation of stomatal aperture. The Arabidopsis histidine kinase
      5 (AHK5) has been shown to regulate stomatal closure in response to H2O2 and
      other stimuli that depend on H2O2. AHK5 is a member of the two-component system
      (TCS) in Arabidopsis. The plant TCS comprises three different protein types: the
      hybrid histidine kinases (HKs), the phosphotransfer proteins (HPs) and the
      response regulators (RRs). Here we determined TCS elements involved in H2O2- and
      ethylene-dependent stomatal closure downstream of AHK5. By yeast and in planta
      interaction assays and functional studies, AHP1, 2 and 5 as well as the response
      regulators ARR4 and ARR7 were identified acting downstream of AHK5 in the
      ethylene and H2O2 response pathways of guard cells. Furthermore, we demonstrate
      that aspartate phosphorylation of ARR4 is only required for the H2O2- but not for
      the ethylene-induced stomatal closure response. Our data suggest the presence of
      a complex TCS signaling network comprising of at least AHK5, several AHPs and
      response regulators, which modulate stomatal closure in response to H2O2 and
      ethylene.

PMID- 22951400
TI  - Evidence that the Arabidopsis Ubiquitin C-terminal Hydrolases 1 and 2 associate
      with the 26S proteasome and the TREX-2 complex.
AB  - The 26S proteasome interacts with a number of different proteins, while the TREX
      2 complex is an important component of the mRNA export machinery. In animals and
      yeast, members of the Ubiquitin C-terminal Hydrolase 37 (UCH37) family are found
      to associate with the 26S proteasome, but this has not been demonstrated in
      plants. The Arabidopsis UCH1 and UCH2 are orthologous to UCH37. Here, we show
      that UCH1 and UCH2 interact with the 26S proteasome lid subunits. In addition,
      the two UCHs also interact with TREX-2 components. Our data suggest that
      Arabidopsis UCHs may serve as a link between the 26S proteasome lid complex and
      the TREX-2 complex.

PMID- 22951401
TI  - The class II HD-ZIP JAIBA gene is involved in meristematic activity and important
      for gynoecium and fruit development in Arabidopsis.
AB  - Development and patterning of the gynoecium - and later the fruit - must be
      finely regulated to ensure the survival of the species that produces them. The
      process that leads to successful fruit formation starts at early stages of floral
      meristem development and follows a series of chronologically successive events.
      In a recent work we reported the functional characterization of the class II HD
      ZIP JAIBA (JAB) gene. Mutant jab plants showed sporophytic defects in male and
      female reproductive development, and combined with the mutant crabs claw (crc)
      caused defects in the floral meristem (FM) determination process and gynoecium
      medial tissue development. Furthermore, the JAB protein interacted with
      transcription factors known to regulate meristematic activity, fruit development
      and FM determinacy. Preliminary results presented here suggest a genetic
      interaction between JAB and the gene SHOOT MERISTEMLESS (STM).

PMID- 22951403
TI  - Plant intentionality and the phenomenological framework of plant intelligence.
AB  - This article aims to bridge phenomenology and the study of plant intelligence
      with the view to enriching both disciplines. Besides considering the world from
      the perspective of sessile organisms, it would be necessary, in keeping with the
      phenomenological framework, to rethink (1) the meaning of being-sessile and being
      in-a-place; (2) the concepts of sentience and attention; (3) how aboveground and
      underground environments appear to plants; (4) the significance of modular
      development for our understanding of intelligence; and (5) the concept of
      communication within and between plants and plant tissues. What emerges from
      these discussions is the image of a mind embodied in plant life.

PMID- 22951402
TI  - Role of proline under changing environments: a review.
AB  - When exposed to stressful conditions, plants accumulate an array of metabolites,
      particularly amino acids. Amino acids have traditionally been considered as
      precursors to and constituents of proteins, and play an important role in plant
      metabolism and development. A large body of data suggests a positive correlation
      between proline accumulation and plant stress. Proline, an amino acid, plays a
      highly beneficial role in plants exposed to various stress conditions. Besides
      acting as an excellent osmolyte, proline plays three major roles during stress,
      i.e., as a metal chelator, an antioxidative defense molecule and a signaling
      molecule. Review of the literature indicates that a stressful environment results
      in an overproduction of proline in plants which in turn imparts stress tolerance
      by maintaining cell turgor or osmotic balance; stabilizing membranes thereby
      preventing electrolyte leakage; and bringing concentrations of reactive oxygen
      species (ROS) within normal ranges, thus preventing oxidative burst in plants.
      Reports indicate enhanced stress tolerance when proline is supplied exogenously
      at low concentrations. However, some reports indicate toxic effects of proline
      when supplied exogenously at higher concentrations. In this article, we review
      and discuss the effects of exogenous proline on plants exposed to various abiotic
      stresses. Numerous examples of successful application of exogenous proline to
      improve stress tolerance are presented. The roles played by exogenous proline
      under varying environments have been critically examined and reviewed.

PMID- 22951404
TI  - The three-domain model: a new model for the early development of leaves in
      Arabidopsis thaliana.
AB  - Blade outgrowth and region-specific cell differentiation are crucial events
      during the early development of plant leaves, and the progression of both of
      these events requires a normal adaxial-abaxial pattern. In a recent study, we had
      demonstrated that two WUSCHEL-RELATED HOMEOBOX (WOX) family genes, i.e., PRESSED
      FLOWER (PRS) and WOX1, act redundantly in blade outgrowth and adaxial-abaxial
      patterning. During leaf development, the two genes are expressed in the domain
      between the adaxial and abaxial domains, designated "the middle domain." Together
      with additional data, we recently proposed "the three-domain model" in which the
      middle domain is distinct from the adaxial and abaxial domains and plays a key
      role in blade outgrowth and the pattern formation of the three domains through
      the function of two WOX genes. In this report, we provide three additional
      results that reinforce our model: (1) an expanded pattern of abaxial-specific
      MIR165A expression in prs wox1, (2) a genetic interaction between the two WOX
      genes and adaxial-specific REVOLUTA gene in adaxial-abaxial patterning and (3) an
      altered expression pattern of the middle domain-specific marker, consistent with
      disruption of the adaxial-abaxial pattern.

PMID- 22951405
TI  - Arabidopsis scaffold protein RACK1A modulates rare sugar D-allose regulated
      gibberellin signaling.
AB  - As energy sources and structural components, sugars are the central regulators of
      plant growth and development. In addition to the abundant natural sugars in
      plants, more than 50 different kinds of rare sugars exist in nature, several of
      which show distinct roles in plant growth and development. Recently, one of the
      rare sugars, D-allose, an epimer of D-glucose at C3, is found to suppress plant
      hormone gibberellin (GA) signaling in rice. Scaffold protein RACK1A in the model
      plant Arabidopsis is implicated in the GA pathway as rack1a knockout mutants show
      insensitivity to GA in GA-induced seed germination. Using genetic knockout lines
      and a reporter gene, the functional role of RACK1A in the D-allose pathway was
      investigated. It was found that the rack1a knockout seeds showed hypersensitivity
      to D-allose-induced inhibition of seed germination, implicating a role for RACK1A
      in the D-allose mediated suppression of seed germination. On the other hand, a
      functional RACK1A in the background of the double knockout mutations in the other
      two RACK1 isoforms, rack1b/rack1c, showed significant resistance to the D-allose
      induced inhibition of seed germination. The collective results implicate the
      RACK1A in the D-allose mediated seed germination inhibition pathway. Elucidation
      of the rare sugar signaling mechanism will help to advance understanding of this
      less studied but important cellular signaling pathway.

PMID- 22951406
TI  - The coordinated role of ethylene and glucose in sulfur-mediated protection of
      photosynthetic inhibition by cadmium.
AB  - Ethylene controls photosynthesis and induces tolerance of plants to metal stress.
      However, little is known about the interaction between ethylene, photosynthesis
      and sulfur (S) availability under cadmium (Cd) stress. Recently, we reported that
      ethylene controls photosynthesis by increasing glutathione (GSH) synthesis with
      sufficient-S availability under Cd stress. Plants treated with Cd were less
      sensitive to ethylene and showed photosynthetic inhibition. Ethylene sensitivity
      of plants was increased with exogenously-sourced ethylene or with sufficient-S
      application resulting in induced GSH synthesis and alleviation of photosynthetic
      inhibition by Cd. In this addendum we present some additional data indicating
      that ethylene regulates photosynthesis by reducing glucose (Glc) sensitivity,
      thus reducing the Glc-mediated photosynthetic repression.

PMID- 22951407
TI  - A web-based intervention to improve and prevent low back pain among office
      workers: a randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To test the feasibility,
      safety, and efficacy of a web-based multidisciplinary intervention for office
      workers with subacute, nonspecific low back pain. BACKGROUND: Low back pain is
      one of the most frequent ailments seen in primary care consultations. METHODS:
      The trial included 100 office workers with subacute low back pain. The
      intervention group had access to both the study intervention and standard care.
      The control group had access to standard care only. Standard care was defined as
      all existing non-web-based interventions offered by the University of
      Extremadura's Preventive Medicine Service. The web-based program was offered via
      the Preventive Medicine Service website. The participants in the intervention
      group were asked to engage in the web-based program at their work site for 11
      minutes each day, 5 days a week. Primary outcomes were functional disability, as
      measured by the Roland-Morris Disability Questionnaire, and health-related
      quality of life, as measured by the European Quality of Life-5 Dimensions-3
      Levels. Secondary outcomes were the number of episodes of low back pain and trunk
      muscle endurance. Outcomes were measured before and after the 9-month
      intervention period. RESULTS: Over the 9-month study, the score on the Roland
      Morris Disability Questionnaire for the participants in the web-based
      intervention group improved by a mean of -7.36 points (95% confidence interval
      [CI]: -8.41, -6.31) compared to a worsening of 1.89 points (95% CI: 0.71, 2.65)
      in the control group. The between-group difference in change on the Roland-Morris
      Disability Questionnaire over the study period was -9.25 points (95% CI: -10.57, 
      7.89). Similarly, over the 9-month study, the intervention group had a
      significant improvement in quality of life of 0.24 points (95% CI: 0.20, 0.29)
      compared to the control group. CONCLUSION: A 9-month web-based intervention is
      feasible and effective to improve function and health-related quality of life and
      to decrease episodes of low back pain among office workers with a history of
      subacute, nonspecific low back pain.

PMID- 22951408
TI  - [Helicobacter pylori - 2012].
AB  - The author overviews some aspects of literature data of the past 2 years. Genetic
      research has identified polymorphisms of Helicobacter pylori virulence factors
      and the host which could play a role in the clinical outcome of the infection
      (peptic ulcer or gastric cancer). So far they have been performed in research
      centers but with a decrease of costs, they will take their place in diagnosing
      the diseases and tailoring the treatment. Antibiotic resistance is still growing
      in Southern European countries and is decreasing in Belgium and Scandinavia.
      Currently, the clarithromycin resistance rate is of 17-33% in Budapest and
      levofloxacin resistance achieved 27%. With careful assessment of former
      antibiotic use the resistance to certain antibiotics can be avoided and the rates
      of eradication improved. Immigration is a growing problem worldwide: according to
      Australian, Canadian and Texan studies, the prevalence of Helicobacter pylori is
      much higher in the immigrant groups than in the local population. An Italian
      study showed that the eradication rate of triple therapy is significantly lower
      in the Eastern European immigrants than in the Italians. A recent research has
      suggested a link between female/male infertility, habitual abortion and
      Helicobacter pylori infection. However, there are no published data or personal
      experience to show whether successful eradication of the virus in these cases is
      followed by successful pregnancies or not. The author overviews the Maastricht
      process and analyzes the provisions of the Maastricht IV/Florence consensus, in
      which the new diagnostic algorithms and indications of eradication therapy are
      reformulated according to the latest levels of evidence and recommendation
      grading. According to the "test and treat" strategy, either the urea breath test
      or the stool monoclonal antigen test are recommended as a non-invasive diagnostic
      method in primary care. Endoscopy is still recommended in case of alarm symptoms,
      complicated ulcer, or if there is a suspicion of malignancy or MALT lymphoma.
      Local resistance to clarithromycin and levofloxacin should be considered in the
      choice of first-line therapy, in case of levels >15-20% these compounds should
      not be used. In regions with low resistance rates, classical triple therapy
      remains the regimen of choice; its alternative is the bismuth-based quadruple
      therapy. Determining antimicrobial resistance is justified after failed second-
      or third-line therapies; where available, molecular methods (fluorescence in situ
      hybridization, polymerase chain reaction) should be used. As second/third line
      treatments, the sequential, bismuth-based quadruple, concomitant quadruple
      regimens, hybrid are all possible alternatives. The Hungarian diagnostic and
      therapeutic approach in practice is different in some aspects from the provisions
      of the European consensus. Orv. Hetil., 2012, 153, 1407-1418.

PMID- 22951409
TI  - [The importance of fine needle aspiration cytology in the management of recurrent
      and metastatic melanoma].
AB  - Fine needle aspiration cytology is a widely accepted, reliable diagnostic
      modality for the early detection of metastases. OBJECTIVE: Quality assurance
      analysis of fine needle aspiration cytology in melanoma patients. METHOD: A total
      of 194 biopsies performed in 142 melanoma patients were analyzed retrospectively.
      RESULTS: 138 (71.13%) cutaneous or subcutaneous nodules and 56 (28.87%) palpable
      lymph nodes were studied. 87 (44.85%) true positive, 92 (47.42%) true negative, 3
      (1.55%) false positive and 12 (6.19%) false negative cytology results were found.
      High sensitivity (87.89%), specificity (96.84%) and diagnostic accuracy (93.72%)
      were confirmed. DISCUSSION: The quality assurance of fine needle aspiration
      biopsy in these patients with recurrent and metastatic melanoma meets the
      international requirements.

PMID- 22951410
TI  - [Acute mesenteric ischemia: analysis of cases over a ten-years period (2001
      2010)].
AB  - Acute mesenteric ischemia is a rare disorder; it occurs on average of 0.4% of
      acute surgery cases. Its diagnosis is often difficult because of the poor
      symptoms, and mortality of the patients is still as high as 70-90%. AIMS: The
      aims of the study were to assess the importance of time factor that may influence
      the outcome and to find out whether it is possible to decrease the high mortality
      rate in this disease. METHOD: Among patients admitted to Saint Pantaleon Hospital
      in Hungary between January 2001 and December 2010, patients whose surgery or
      autopsy findings confirmed intestinal necrosis were analyzed. A total of 114
      patients with acute mesenteric ischemia were included in the study. RESULTS: 55%
      of the patients had typical symptoms. 43.8% of the patients underwent surgery and
      among these patients the mortality rate was 70% despite surgical intervention.
      The survival rate was 72.3% when surgery was performed within less than 12 hours
      after the onset of symptoms, but only 20% of patients survived when surgery was
      delayed between 24 and 48 hours after the onset of symptoms. CONCLUSION: With
      early diagnosis and intervention, patients with acute mesenteric ischemia may
      have a better a chance to survive.

PMID- 22951411
TI  - [Market oriented occupational medicine].
AB  - The history and the recent state of occupational medicine in Hungary, and its
      relation with governmental labor organizations are analyzed. In the past 20
      years, large "socialist" factories were replaced by smaller companies employing
      fewer workers. They have been forced to establish contract with occupational
      health providers. Many of them offer primary care services, whereas family
      physicians having a board examination in occupational medicine are allowed to
      work in this field as well. The market of occupational medicine is less
      regulated, and ethical rules are not always considered. Undercutting prices is a
      common practice. The recent system could be improved by some regulations which
      should be respected. There is no reason to make rough changes establishing a new
      market for profit oriented insurance companies, and to allow employees and
      employers to work without specification neglecting international agreements.
      Occupational medicine should be supervised again by the health authorities
      instead of economists who have quite different, short-term priorities.

PMID- 22951412
TI  - [Caesarean section in the medieval British Isles].

PMID- 22951414
TI  - Heterotypic three-dimensional in vitro modeling of stromal-epithelial
      interactions during ovarian cancer initiation and progression.
AB  - Epithelial ovarian cancers (EOCs) are the leading cause of death from
      gynecological malignancy in Western societies. Despite advances in surgical
      treatments and improved platinum-based chemotherapies, there has been little
      improvement in EOC survival rates for more than four decades. Whilst stage I
      tumors have 5-year survival rates >85%, survival rates for stage III/IV disease
      are <40%. Thus, the high rates of mortality for EOC could be significantly
      decreased if tumors were detected at earlier, more treatable, stages. At present,
      the molecular genetic and biological basis of early stage disease development is
      poorly understood. More specifically, little is known about the role of the
      microenvironment during tumor initiation; but known risk factors for EOCs (e.g.
      age and parity) suggest that the microenvironment plays a key role in the early
      genesis of EOCs. We therefore developed three-dimensional heterotypic models of
      both the normal ovary and of early stage ovarian cancers. For the normal ovary,
      we co-cultured normal ovarian surface epithelial (IOSE) and normal stromal
      fibroblast (INOF) cells, immortalized by retrovrial transduction of the catalytic
      subunit of human telomerase holoenzyme (hTERT) to extend the lifespan of these
      cells in culture. To model the earliest stages of ovarian epithelial cell
      transformation, overexpression of the CMYC oncogene in IOSE cells, again co
      cultured with INOF cells. These heterotypic models were used to investigate the
      effects of aging and senescence on the transformation and invasion of epithelial
      cells. Here we describe the methodological steps in development of these three
      dimensional model; these methodologies aren't specific to the development of
      normal ovary and ovarian cancer tissues, and could be used to study other tissue
      types where stromal and epithelial cell interactions are a fundamental aspect of
      the tissue maintenance and disease development.

PMID- 22951416
TI  - Characterization of lipid and lipoprotein metabolism in primary human
      hepatocytes.
AB  - Primary rodent hepatocytes and hepatoma cell lines are commonly used as model
      systems to elucidate and study potential drug targets for metabolic diseases such
      as obesity and atherosclerosis. However, if therapies are to be developed, it is
      essential that our knowledge gained from these systems is translatable to that of
      human. Here, we have characterized lipid and lipoprotein metabolism in primary
      human hepatocytes for comparison to rodent primary hepatocytes and human hepatoma
      cell lines. Primary human hepatocytes were maintained in collagen coated dishes
      in confluent monolayers for up to 3 days. We found primary human hepatocytes were
      viable, underwent lipid synthesis, and were able to secret lipoproteins up to 3
      days in culture. Furthermore, the lipoprotein profile secreted by primary human
      hepatocytes was comparable to that found in human plasma; this contrasts with
      primary rodent hepatocytes and human hepatoma cells. We also investigated the
      pharmacological effects of nicotinic acid (niacin, NA), a potent dyslipidemic
      drug, on hepatic lipid synthesis and lipoprotein secretion. We found NA increased
      the expression of ATP-binding cassette transporter A1 in primary human
      hepatocytes, which may potentially explain how NA increases plasma high-density
      lipoproteins in humans. In conclusion, primary human hepatocytes are a more
      relevant model to study lipid synthesis and lipoprotein secretion than hepatoma
      cells or rodent primary hepatocyte models. Further research needs to be done to
      maintain liver specific functions of primary human hepatocytes in prolonged
      cultures for these cells to be a viable model.

PMID- 22951415
TI  - Effect of BAX499 aptamer on tissue factor pathway inhibitor function and thrombin
      generation in models of hemophilia.
AB  - INTRODUCTION: In hemophilia, thrombin generation is significantly suppressed due
      to decreased factor (F)X activation. Clinical studies and experiments with
      transgenic mice have suggested that the severity of hemophilia is substantially
      reduced by tissue factor pathway inhibitor (TFPI) deficiency. METHODS: We
      evaluated the effect of TFPI antagonist aptamer BAX499 (formerly ARC19499) on
      TFPI function in purified systems and on thrombin generation and clot formation
      in plasma and blood. RESULTS: BAX499 effectively neutralized TFPI inhibition of
      FXa and FXa dependent inhibition of TF/FVIIa by TFPI. BAX499 did not inhibit FXa
      or TF/FVIIa when used up to 500 nM. In the synthetic coagulation proteome with
      TFPI at its mean physiologic concentration, BAX499 at 1 - 10nM increased thrombin
      generation triggered with 5 pM relipidated TF in a concentration-dependent
      manner. In severe hemophilia A or B models using the synthetic coagulation
      proteome, the addition of BAX499 at 5 nM increased thrombin generation to the
      levels observed in normal control. Thrombin generation measured in induced
      hemophilia B plasma required ~100nM BAX499 to restore thrombin levels to those
      seen in untreated plasma. In induced hemophilia B whole blood, BAX499 repaired
      the clotting time but failed to appreciably impact the propagation phase of
      thrombin generation. CONCLUSION: These data suggest that inhibition of TFPI by
      BAX499 may have potential for hemophilia treatment but requires further study in
      blood-based hemophilia systems.

PMID- 22951417
TI  - A new long term hepatic complication in survivors of childhood haematological
      malignancy.
AB  - Hepatic abnormalities have been documented in survivors of childhood malignancies
      and a spectrum of liver diseases has been described in this group The risk
      factors for liver disease include: hepatic surgery; radiotherapy to field
      including liver; total body irradiation (TBI); chemotherapy, multiple blood
      transfusions and use of hematopoietic cell transplantation. We report three cases
      of hepatic adenomatosis (HA) in young women who had been treated for
      haematological malignancy as children and had bone marrow transplant. These women
      were on estrogen and growth hormone replacement. They had mild abnormalities of
      liver function tests. The diagnosis of HA was made on liver imaging and confirmed
      by liver biopsy. We also propose a hypothesis for the pathogenesis of hepatic
      adenomatosis in these patients which vascular damage, estrogen replacement and
      growth hormone deficiency.

PMID- 22951418
TI  - Increased nuclear factor-kappaB and loss of p53 are key mechanisms in Myalgic
      Encephalomyelitis/chronic fatigue syndrome (ME/CFS).
AB  - Fukuda's criteria are adequate to make a distinction between Myalgic
      Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and chronic fatigue (CF), but
      ME/CFS patients should be subdivided into those with (termed ME) and without
      (termed CFS) post exertional malaise [Maes et al. 2012]. ME/CFS is considered to
      be a neuro-immune disease. ME/CFS is characterized by activated immuno
      inflammatory pathways, including increased levels of pro-inflammatory cytokines,
      nuclear factor kappaB (NF-kappaB) and aberrations in mitochondrial functions,
      including lowered ATP. These processes may explain typical symptoms of ME/CFS,
      e.g. fatigue, malaise, hyperalgesia, and neurologic and autonomic symptoms. Here
      we hypothesize that increased NF-kappaB together with a loss of p53 are key
      phenomena in ME/CFS that further explain ME/CFS symptoms, such as fatigue and
      neurocognitive dysfunction, and explain ME symptoms, such as post-exertional
      malaise following mental and physical activities. Inactivation of p53 impairs
      aerobic mitochondrial functions and causes greater dependence on anaerobic
      glycolysis, elevates lactate levels, reduces mitochondrial density in skeletal
      muscle and reduces endurance during physical exercise. Lowered p53 and increased
      NF-kappaB are associated with elevated reactive oxygen species. Increased NF
      kappaB induces the production of pro-inflammatory cytokines, which increase
      glycolysis and further compromise mitochondrial functions. All these factors
      together may contribute to mitochondrial exhaustion and indicate that the demand
      for extra ATP upon the commencement of increased activity cannot be met. In
      conditions of chronic inflammation and oxidative stress, high NF-kappaB and low
      p53 may conspire to promote neuron and glial cell survival at a price of severely
      compromised metabolic brain function. Future research should examine p53
      signaling in ME/CFS.

PMID- 22951419
TI  - Characteristics of high-quality Asian elephant (Elephas maximus) ejaculates and
      in vitro sperm quality after prolonged chilled storage and directional freezing.
AB  - The in vitro quality of spermatozoa from one elephant (Elephas maximus) was
      examined after chilled storage and directional freezing (DF). High-quality, non
      contaminated ejaculates (77.6+/-6.0% progressive motility, 3.9+/-1.5 ug
      creatinine mL(-1) raw semen, 2.7+/-0.6% detached heads) were cryopreserved after
      0 (0hStor), 12 (12hStor) and 24 h (24hStor) of chilled storage. At 0 h and 6h
      post-thawing, total motility, plasma membrane integrity, acrosome integrity,
      mitochondrial activity and normal morphology were similar (P>0.05) across
      treatments. In contrast, progressive motility, rapid velocity and several
      kinematic parameters were lower (P<0.05) for 24Stor compared with 0hStor at 0 h
      post-thaw. By 6 h post-thaw, amplitude of lateral head displacement and velocity
      parameters (average pathway, straight-line and curvilinear velocity) were lower
      (P<0.05) for 24hStor compared with 0hStor and 12hStor. DNA integrity was high and
      remained unchanged (P>0.05) across all groups and processing stages (1.6+/-0.6%
      of cells contained fragmented DNA). Results indicate that DF after up to 12 h of
      chilled storage results in a post-thaw sperm population of acceptable quality for
      artificial insemination. These findings have implications for the
      cryopreservation of sex-sorted spermatozoa, which typically undergo more than 12
      h of chilled storage prior to sorting and preservation.

PMID- 22951420
TI  - Outcome of lamivudine-resistant chronic hepatitis B after up to 5 years of
      combination therapy with adefovir.
AB  - BACKGROUND: There is a paucity of data on the long-term efficacy of combination
      lamivudine and adefovir therapy in patients with lamivudine-resistant chronic
      hepatitis B. METHODS: We determined the cumulative virological, serological and
      biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on
      lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe
      assay were determined among patients with detectable viraemia. The significance
      of different baseline and on-treatment virological parameters was analysed.
      RESULTS: The median age and duration of follow-up were 45.1 years and 37.1
      months, respectively. The cumulative rates of HBV DNA undetectability (<20
      IU/ml), alanine aminotransferase normalization and hepatitis B e antigen
      seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One
      patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative
      resistance rate to adefovir was 10.2%. Among different baseline and on-treatment
      virological parameters, week 24 HBV DNA<200 IU/ml was associated with an
      increased chance of long-term virological suppression (P<0.001, OR 13.89, 95% CI
      3.90, 49.46). Primary non-response and high baseline viral titres were not useful
      in predicting long-term virological outcomes. The 5-year cumulative rate of serum
      creatinine elevation >0.5 mg/dl was 4.1%. CONCLUSIONS: Combination lamivudine and
      adefovir therapy for up to 5 years achieved modest rates of virological
      suppression, but resistance developed in only 10.2% of patients. Week 24 HBV
      DNA<200 IU/ml was predictive of favourable long-term virological outcomes and
      could be used to assist treatment decisions on continuing lamivudine and adefovir
      or switching to more potent therapy.

PMID- 22951421
TI  - Students' perceptions of the follow-through experience in 3 year bachelor of
      midwifery programmes in Australia.
AB  - BACKGROUND: providing opportunities for students to participate in midwifery
      continuity of care experiences is a challenge in many midwifery education
      programmes. The 'follow-through experience' was a deliberate strategy introduced
      into midwifery education programmes in Australia to ensure that students
      experienced midwifery continuity of care. The follow through experience provides
      an opportunity for midwifery students to follow a pre-determined number of women
      through pregnancy, labour and birth and into the early parenting period. AIM: the
      aim of this study was to explore the follow-through experience in the 3 year
      Bachelor of Midwifery (direct entry) in Australia to better understand its impact
      on midwifery students and to identify the learning that is associated with this
      experience. METHODS: a qualitative methodology was used. Data were collected from
      former and current Bachelor of Midwifery students through a survey and telephone
      interviews. Students from all 3-year pre-registration Bachelor of Midwifery
      programmes in Australia were invited to participate. A thematic analysis was
      undertaken. Constructivist learning theories were used to identify whether
      learning occurred in the context of the follow-through experience. FINDINGS:
      students do learn from their engagement in midwifery continuity of care
      experiences. Learning was characterised by the primacy of the relationship with
      the women. Students also identified the challenges they faced which included
      recruitment of women and finding the time to fully engage with the follow-through
      experience. Difficulties were identified around the different requirements of the
      follow-through experience, the lack of support at times for students and the
      incongruence with the existing maternity system. These issues impacted on
      students' ability to engage in and maximise their learning. CONCLUSIONS: the
      follow-through experience is an innovative midwifery education strategy that
      facilitates learning for midwifery students. Challenges need to be addressed at a
      systematic level and new strategies developed to support the learning
      opportunities presented by the follow-through experience.

PMID- 22951422
TI  - Midwives perspectives of their training and education requirements in maternal
      obesity: a qualitative study.
AB  - OBJECTIVE: to explore midwives' perceptions of their training and education
      requirements in relation to maternal obesity. DESIGN: an interpretive
      constructionist approach used focus groups and broad discussion topics to allow
      midwives to identify their own personal and professional needs. Data analysis
      incorporated researcher and data triangulation (transcripts, debrief notes, and
      observers' notes), using a thematic content analysis approach. SETTING AND
      PARTICIPANTS: participants included 46 community and hospital-based midwives from
      all NHS Trusts providing maternity services in Northeast England, UK. Eleven
      focus groups took place in midwives' place of work. Sampling was determined by
      data saturation. FINDINGS: three main themes were identified: discussing obesity,
      weight management, and practicalities of training. Midwives' justification for
      the need for training was centrally connected to all themes, and there were
      strong views on the need for training and education, and the potential benefits
      to their practice. Issues relating to obesity communication were most prominent.
      Midwives' uncertainty about effective obesity communication and management, and
      concerns of a negative impact on the midwife-woman relationship, are key barriers
      to their practice. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the provision
      of a systematic approach to training and education is endorsed by midwives, and
      would provide the required level of knowledge and skills to deliver the
      recommended standard of care appropriate to their practice. It is clear that
      midwives require both training and education, although there are challenges to
      midwives' engagement with effective continuous professional development largely
      outside their control. Realistic models of training and education are required to
      address midwives' needs, and these should be thoroughly evaluated for impact on
      midwifery practice, and on obese women's health and well-being.

PMID- 22951423
TI  - The methodological challenges of attempting to compare the safety of home and
      hospital birth in terms of the risk of perinatal death.
AB  - This paper identifies a number of methodological difficulties associated with the
      comparison of home and hospital birth in terms of the risk of perinatal death,
      and suggests ways in which these problems can be overcome. A review of recent
      studies suggests that most available data sources are unable to overcome all of
      these challenges, which is one of the reasons why the debate about whether
      perinatal death is more likely if a home birth is planned or if a hospital birth
      is planned has not been satisfactorily resolved. We argue that the debate will be
      settled only if perinatal mortality data from a sufficiently large number of
      maternity care providers over a sufficiently long period of time can be pooled
      and made available for analysis. The pooling of data will bring about its own
      difficulties due to variations over time and between providers and geographical
      areas, which would need to be taken into account when analysing pooled data.
      However, given the impracticality of a randomised controlled trial and the rarity
      of home birth in most of the Western world, we argue that more effort should be
      made to pool data for perinatal mortality and other rare pregnancy outcomes, and
      share them between health providers and researchers. Thus, high-quality analyses
      could be conducted, allowing all women to make an informed choice about place of
      birth. However, pooling data from countries or states with very different
      maternity care systems should be avoided.

PMID- 22951425
TI  - Immunogenetics of human echinococcosis.
AB  - Susceptibility and resistance to human Echinococcus infection and disease,
      although poorly understood, appear to reflect a complex interaction of parasite
      and host immunological and genetic factors. Disease stage, progression, and
      prognosis following treatment appear to be strongly influenced by cytokine and
      antibody profiles, and more recent evidence has suggested an important role of
      dendritic cells (DCs) and T regulatory cells (Tregs) in immunomodulation.
      Microarrays have supported these findings, highlighting both known and novel
      pathways involved in chronic murine disease. Genetic studies to date have been
      few and with limited success. Advanced genomic approaches, such as genome-wide
      association studies (GWAS), may provide further insight to identify the relevant
      pathways involved, thereby facilitating a new approach for the development of new
      clinical therapies.

PMID- 22951424
TI  - The diverse roles of monocytes in inflammation caused by protozoan parasitic
      diseases.
AB  - The mononuclear phagocyte system (MPS), comprising monocytes, macrophages, and
      dendritic cells (DCs), plays an important role in the control of disease, but can
      also contribute to the establishment of persistent infections. Monocytes are
      derived from progenitors in the bone marrow. Once in circulation, they migrate
      into the tissues, differentiate into macrophages, and phagocytose microbes under
      inflammatory conditions. However, recent work shows they not only act as
      phagocytes, but are also precursors for particular types of DCs, inflammatory
      macrophages, and tissue macrophages. The role of monocytes during inflammation in
      models of bacterial and viral infections, cancer, atherosclerosis, and
      autoimmunity has been widely studied and reported. In this review we focus on the
      less understood role of monocytes in protozoan infections.

PMID- 22951426
TI  - A prospective, randomized, double dummy, placebo-controlled trial of oral
      cefditoren pivoxil 400mg once daily as switch therapy after intravenous
      ceftriaxone in the treatment of acute pyelonephritis.
AB  - OBJECTIVES: To compare the clinical and bacteriological effectiveness of
      intravenous (IV) ceftriaxone followed by oral cefditoren pivoxil or IV
      ceftriaxone for acute pyelonephritis. METHODS: A prospective randomized
      controlled trial of patients with a presumptive diagnosis of acute pyelonephritis
      was performed. Daily 2g IV ceftriaxone was initially given to all patients. After
      day 3, patients who satisfied the criteria for switch therapy were randomized to
      either group A (IV ceftriaxone) or group B (oral cefditoren pivoxil 400mg once
      daily). RESULTS: Eighty-two patients were enrolled; 41 (50%) patients in group A
      and 41 (50%) patients in group B were evaluated. There was no statistically
      significant difference in baseline characteristics between the two groups.
      Clinical cure was observed in 39 of 41 (95.1%) patients in group A and 41 of 41
      (100%) patients in group B (p=0.15, 95% confidence interval (CI) -0.12 to 0.02).
      Urine bacteriological eradication was found in 63.4% in group A and 60% in group
      B (p=0.75, 95% CI -0.18 to 0.25). There was no statistically significant
      difference in adverse effects between the two treatment groups. CONCLUSION: These
      data suggest that IV ceftriaxone followed by oral cefditoren pivoxil is highly
      effective and well-tolerated for the treatment of acute pyelonephritis, even for
      uropathogens with a high proportion of quinolone-resistant strains.

PMID- 22951427
TI  - Prevalence, pattern, and determinants of placental malaria in a population of
      southeastern Nigerian parturients.
AB  - BACKGROUND: Placental malaria is a complication of malaria in pregnancy and is
      associated with adverse outcomes. Its burden is highest in Sub-Saharan Africa,
      but despite this, data based on histological analysis are scarce from this
      region. METHODS: Questionnaires administered by the researchers were used to
      obtain information from parturients at a university teaching hospital in
      southeastern Nigeria between April and November 2010. Maternal blood and
      placental blood were collected for analysis. Placental blocks were taken for
      histological analysis. Statistical analyses were done using SPSS v. 17. RESULTS:
      Three hundred and sixty-five placentas were analyzed, out of which 254 showed
      histological evidence of malaria parasitization, giving a prevalence of 69.6%. Of
      the 254 placentas, 23 (9.0%) showed active infection and 196 (77.2%) showed
      active-on-past infection, while 35 (13.8%) showed past infection. Rural
      residence, hemoglobin genotype AA, not receiving intermittent preventive
      treatment in pregnancy (IPTp), and not sleeping under insecticide-treated bed
      nets (ITN) were significantly associated with placental malaria. Placental
      parasite density was inversely related to parity. CONCLUSIONS: This study showed
      that the prevalence of placental malaria in southeastern Nigeria is high, and
      demonstrated that the mean parasite density was inversely related to parity.
      Significant factors associated with placental malaria were also identified.
      Appreciation of these significant factors will assist program managers in
      implementing the strategies for the prevention of malaria in pregnancy.

PMID- 22951428
TI  - Functional outcomes of chemoradiation in patients with head and neck cancer.
AB  - OBJECTIVE: Concurrent chemoradiotherapy (CCRT) has become the treatment of choice
      for oropharyngeal and hypopharyngolaryngeal cancers in many centers. Although it
      has increased the rates of organ preservation, there has also been an increase in
      treatment-related complications. We aimed to evaluate the functional outcomes of
      CCRT in head and neck cancer. STUDY DESIGN: Case series with chart review.
      SETTING: Tertiary cancer center. SUBJECTS AND METHODS: A retrospective study of
      patients treated with CCRT at the University of Arkansas for Medical Sciences was
      performed. Demographic data and treatment outcomes were extracted, specifically
      feeding tube and tracheotomy dependence and number of esophageal dilatations.
      RESULTS: Of the 243 patients treated with concurrent chemoradiotherapy (5
      fluorouracil + cysplatin and radiotherapy), 152 patients received a feeding tube.
      The median percutaneous gastrostomy tube (PEG) use was 9 months (range, 1-96
      months). More than 70% of the patients who had a PEG more than 6 months had a T3
      or T4 tumor. Thirty-seven patients underwent esophageal dilatations, (median, 1;
      range, 1-7). The median use of a tracheotomy was 7 months, and 77% of these
      patients were treated for hypopharyngolaryngeal cancer. CONCLUSIONS: Despite
      major improvement in locoregional control rates, CCRT has a significant negative
      impact on the functional outcomes of head and neck cancer patients, with a high
      number of patients remaining PEG and tracheotomy dependent.

PMID- 22951429
TI  - The application of CT to localize the upper airway obstruction plane in patients
      with OSAHS.
AB  - OBJECTIVE: To identify a correlation in terms of airway obstruction between awake
      and sleep apnea using spiral computed tomography (CT). STUDY DESIGN: Case series
      with planned data collection. SETTING: College medical center. METHODS: Sixty-one
      patients diagnosed with obstructive sleep apnea/hypopnea syndrome (OSAHS)
      underwent CT scans under 3 conditions: quiet breathing while awake, the end of
      deep inspiration during wakefulness, and apnea while asleep. The upper airway
      morphology under the 3 conditions was compared, and the accuracy of the
      obstructive planes as determined by CT scans under the 2 awake conditions was
      analyzed while considering the obstructive planes that occurred during apnea as a
      reference. RESULTS: The differences in the anteroposterior diameter, lateral
      dimension, and cross-sectional area of the retropalatal and retroglossal regions
      among the 3 states were statistically significant. Obstruction of the
      retropalatal region occurred in 100%, whereas retroglossal obstruction occurred
      in 44.3% of the 61 cases during sleep apnea. The coincidence rate between the
      awake quiet breathing and the sleep apnea was 85.2% in the retropalatal
      obstruction and 52.5% in the retroglossal obstruction. The coincidence rate
      between the awake deep inspiration and the sleep apnea was 82.0% in the
      retropalatal obstruction and 54.1% in the retroglossal obstruction. CONCLUSION:
      The main obstructive plane in patients with OSAHS was the retropalatal region. An
      awake upper airway CT scan can properly diagnose palatopharyngeal obstruction;
      however, it is not suitable for detecting retroglossal obstruction.

PMID- 22951430
TI  - Tympanoplasty for blast-induced perforations: the Walter Reed experience.
AB  - OBJECTIVE: To review our tympanoplasty results for blast-induced tympanic
      membrane perforations and evaluate the association of various clinical factors
      with surgical success. STUDY DESIGN: Case series with chart review. SETTING: Two
      tertiary military healthcare institutions. METHODS: This is a retrospective
      review of all patients who had nonrevision tympanoplasty during a 1-year period
      for blast-induced perforations by the 2 neurotologists at Walter Reed Army
      Medical Center and National Naval Medical Center. Various perioperative clinical
      factors were analyzed for relations to successful perforation closure, the need
      for a second operation, and postoperative hearing. RESULTS: Thirty-four patients
      met inclusion criteria. All were male, and the average age was 24.0 years. Twenty
      two (65%) were total or near-total perforations, of which 12 (35%) were repaired
      using lateral graft technique. The remainder had various medial graft procedures.
      Ossicular abnormalities were found in 6 (18%) patients. Cholesteatoma was
      discovered in 3 (9%) patients. Closure was complete in 82% of patients. The
      incomplete closures were with large perforations, those with foreign bodies
      (shrapnel), and in 1 with postoperative water exposure. There were no major
      complications, and the mean conductive hearing improvement was 11.3 dB.
      CONCLUSION: Blast-induced tympanic membrane perforations are common in our
      population of wounded warriors. These cases are challenging because most have
      total or near-total perforations, the ossicles can be out of place, the blast
      itself can implant epithelium in the middle ear, and foreign bodies can create a
      hostile middle ear environment. However, given attention to detail, we found that
      standard tympanoplasty techniques work well.

PMID- 22951431
TI  - Ambulatory office visits and medical comorbidities associated with obstructive
      sleep apnea.
AB  - OBJECTIVE: (1) Understand the epidemiology of obstructive sleep apnea (OSA)
      ambulatory office visits in the United States. (2) Quantify the prevalence of
      comorbid illnesses that are likely to occur in the setting of OSA. METHODS: From
      the 2008-2009 National Ambulatory Medical Care Surveys and National Hospital
      Ambulatory Medical Care Surveys, adult cases with a diagnosis of OSA were
      extracted. The epidemiology of OSA was determined. The prevalences of comorbid
      priority illnesses (obesity, asthma, cerebrovascular disease, depression,
      hypertension, and ischemic heart disease) were also determined. STUDY DESIGN:
      Cross-sectional analysis of a national survey database. SETTING: Ambulatory care
      settings in the United States. RESULTS: There were an estimated 4.1 +/- 1.2
      million annual visits with a diagnosis of OSA (60% +/- 3.2% men; mean age, 56.4
      +/- 0.9 years). There were 419,000 +/- 28,000 visits annually to
      otolaryngologists for OSA. Comorbid illnesses were obesity (23.8% +/- 5.2%),
      asthma (14.3% +/- 3.0%), cerebrovascular disease (2.5% +/- 1.5%), depression
      (23.2% +/- 2.6%), hypertension 53.8% +/- 3.9%), and ischemic heart disease (10.3%
      +/- 3.0%). Adjusting for age, sex, ethnicity, obesity, and race, statistically
      significant increased odds for the presence of obesity (3.6, P < .001), asthma
      (2.7, P < .001), depression (2.5, P < .001), and hypertension (2.0, P < .001)
      with OSA were noted. Increased odds for cerebrovascular disease and ischemic
      heart disease were not identified (P = .725 and P = .083, respectively).
      CONCLUSION: Obstructive sleep apnea is a relatively common diagnosis in
      ambulatory and otolaryngologic care. It is associated with a significantly
      increased prevalence of several key priority health care conditions in the United
      States. Otolaryngologists and health care providers should be aware of these
      associations, understanding the potentially broad impact of OSA on general
      health.

PMID- 22951432
TI  - Validated assessment tools for pediatric airway endoscopy simulation.
AB  - OBJECTIVE: To determine the interrater reliability and construct validity of 3
      separate assessment tools for assessing trainee skills in pediatric airway
      endoscopy simulation. DESIGN: An Objective Structured Assessment of Technical
      Skills (OSATS) was developed in which examinees were asked to name and assemble
      the airway foreign body instruments and retrieve a foreign body from an infant
      airway mannequin. Each examinee's performance was assessed in a blinded fashion
      by 3 pediatric otolaryngology faculty at separate residency programs using 3
      assessment tools: (1) objective quantifiable measures list (eg, assists needed,
      forceps openings, foreign body drops), (2) 15-point OSATS checklist, and (3)
      Global Rating Index for Technical Skills (GRITS). Setting Otolaryngology
      residency program. Subjects Examinees (medical students, n = 3; otolaryngology
      residents, n = 17; pediatric otolaryngology faculty, n = 3) and raters (n = 3).
      Main Outcome Measures Interrater reliability and construct validity. Results
      Anonymized split-screen videos simultaneously capturing each examinee's
      instrument handling and the endoscopic videos were created for all 23 examinees.
      Nineteen videos were chosen for review by 3 raters. The interrater reliability as
      measured by the intraclass correlation for objective quantifiable measures ranged
      from 0.46 to 0.98. The intraclass correlation coefficient was 0.95 for the 15
      point OSATS checklist and 0.95 for the GRITS; both showed a high degree of
      construct validity with scores correlating with previous experience. Conclusion
      Assessment tools for skills assessments must have high interrater reliability and
      construct validity. When assessing trainee skills in pediatric airway foreign
      body scenarios, the 15-point OSATS checklist developed by this group or the GRITS
      meets these criteria.

PMID- 22951433
TI  - Prognostic value of olfactory bulb volume measurement for recovery in
      postinfectious and posttraumatic olfactory loss.
AB  - OBJECTIVES: Several prognostic factors influencing the recovery from olfactory
      dysfunction have been described. The aim of this study was to investigate whether
      olfactory bulb volume could be used as a new predictor of olfactory recovery in
      postinfectious and posttraumatic olfactory loss. STUDY DESIGN: Cohort study;
      Level of evidence, 4. Setting Tertiary university clinic, department of
      otolaryngology. SUBJECTS AND METHODS: A cohort of 60 patients with postinfectious
      (n = 28) and posttraumatic olfactory loss (n = 32) was investigated. Assessment
      of olfactory function was performed using orthonasal (Sniffin' Sticks test) and
      retronasal psychophysical olfactory tests, at the time of the diagnosis (t1) and
      15 months later (t2). All patients were examined on 3 tesla magnetic resonance
      imaging, and the olfactory bulbs volume was assessed using planimetric contouring
      at the time of the diagnosis (t1). RESULTS: Recovery rate was 25% in patients
      with posttraumatic olfactory loss and 36% in patients with postinfectious
      olfactory loss. There was a correlation between both orthonasal and retronasal
      olfactory testing and the initial measurement of the total olfactory bulb volume.
      In addition, we observed a significant correlation between changes in olfactory
      functions and initial measurement of the total olfactory bulb volume, with larger
      volumes relating to higher improvement of olfactory function. Finally, we found
      that none of the patients with a total olfactory bulb volume of 40 mm(3) or less
      exhibited recovery of olfactory function. CONCLUSION: Olfactory bulb volume seems
      to be a predictor of olfactory recovery in patients with postinfectious and
      posttraumatic olfactory loss.

PMID- 22951434
TI  - A spheroid weighted-axis converter of vestibular schwannoma size: maximum
      diameter and cisternal volume.
AB  - OBJECTIVES: To evaluate spheroid models of vestibular schwannoma (VS) size for
      bidirectional conversion of maximum diameter in the cistern and 3-dimensional
      volume. STUDY DESIGN: Methodological study. SETTING: Academic tertiary referral
      center. SUBJECTS AND METHODS: Magnetic resonance imaging studies from 91 patients
      with VS from 2003 to 2011 were analyzed. Linear measurements defining meatal and
      cisternal components were extracted. Geometrically based conformal models of
      tumor volume were compared with measured tumor volume using a semiautomated
      computerized tracing method. Models were inverted to predict maximum axial
      cisternal length at the level of the internal auditory canal (IAC). RESULTS: A
      spheroid-weighted axis converter (SWC) of VS size was identified by minimizing
      input measurement parameters while maximizing output prediction performance.
      Computation steps of tumor volumes were (1) meatal-measure tumor lengths along
      the IAC and at the porus acusticus and take the average of a cone and cylinder
      and (2) cisternal-measure maximum tumor length in the axial IAC plane, use the
      median major:minor axis ratio of 1.26:1 to estimate minor axis length, take the
      geometric mean of axial dimensions to estimate axis length in the coronal plane,
      and apply input lengths to a spheroid. Performance error of this SWC had
      interquartile ranges of 33% for volume and 2 to 3 mm for maximum cisternal
      length. CONCLUSION: Reporting variability of VS tumor size has made it difficult
      to reconcile outcomes studies. We propose an accessible tool for bidirectional
      conversion of volumetric and linear indices of tumor size to unlock potential for
      meta-analyses of disparate data sets.

PMID- 22951435
TI  - Adherence index to the American Heart Association Diet and Lifestyle
      Recommendation is associated with the metabolic syndrome in Japanese male
      workers.
AB  - BACKGROUND: As Japanese societies rapidly undergo Westernization, the prevalence
      of metabolic syndrome is increasing. We investigated the association between
      dietary habits and the prevalence of metabolic syndrome using a new adherence
      index to optimal dietary habits based on the American Heart Association Diet and
      Lifestyle Recommendation (AHA-DLR). METHODS: We conducted a cross-sectional study
      of 503 male workers who completed a brief food frequency questionnaire. Adherence
      to the AHA-DLR was assessed using a 10-component adherence index (AI-84; a total
      possible score of 84 points). Metabolic syndrome was defined according to the
      most recently published harmonized criteria by the International Diabetes
      Federation in conjunction with the National Heart, Lung, and Blood Institute,
      American Heart Association, World Heart Federation, International Atherosclerosis
      Society, and International Association for the Study of Obesity. RESULTS: The
      prevalence of metabolic syndrome was 26.6% and the AI-84 score ranged from 5 to
      56 points. Subjects with metabolic syndrome had a significantly lower AI-84 score
      compared with those without (27.1 +/- 9.1 vs. 28.9 +/- 9.2, p=0.042). After
      adjusting for age, energy intake, smoking habit and physical activity, a higher
      AI-84 score was associated with a significantly lower prevalence of metabolic
      syndrome, with an odds ratio of 0.778 (95% CI 0.614-0.986, p=0.038) for each 10
      point score increment. CONCLUSIONS: A lower AI-84 score was associated with
      increased prevalence of metabolic syndrome. Our findings support a potential
      beneficial impact of nutritional assessment using adherence to the AHA-DLR for
      prevention of metabolic syndrome.

PMID- 22951436
TI  - Spectral editing in 13C solid-state NMR at high magnetic field using fast MAS and
      spin-echo dephasing.
AB  - A simple method is proposed for separating NMR resonances from protonated and non
      protonated aromatic carbons in solids under fast magic angle spinning (MAS). The
      approach uses a MAS-synchronized spin-echo to exploit the differences in
      rotational recoupling of the dipolar interactions while fully refocusing the
      isotropic chemical shifts. This strategy extends the relevant time scale of spin
      evolution to milliseconds and circumvents the limitation of the traditional
      dipolar dephasing method, which in fast rotating solids is disrupted by
      rotational refocusing. The proposed approach can be used for quantitative
      measurement of carbon aromaticities in complex solids with poorly resolved
      spectra, as demonstrated for model compounds.

PMID- 22951437
TI  - Return to preinjury sports participation following anterior cruciate ligament
      reconstruction: contributions of demographic, knee impairment, and self-report
      measures.
AB  - STUDY DESIGN: Cross-sectional cohort. OBJECTIVES: (1) To examine differences in
      clinical variables (demographics, knee impairments, and self-report measures)
      between those who return to preinjury level of sports participation and those who
      do not at 1 year following anterior cruciate ligament reconstruction, (2) to
      determine the factors most strongly associated with return-to-sport status in a
      multivariate model, and (3) to explore the discriminatory value of clinical
      variables associated with return to sport at 1 year postsurgery. BACKGROUND:
      Demographic, physical impairment, and psychosocial factors individually prohibit
      return to preinjury levels of sports participation. However, it is unknown which
      combination of factors contributes to sports participation status. METHODS:
      Ninety-four patients (60 men; mean age, 22.4 years) 1 year post-anterior cruciate
      ligament reconstruction were included. Clinical variables were collected and
      included demographics, knee impairment measures, and self-report questionnaire
      responses. Patients were divided into "yes return to sports" or "no return to
      sports" groups based on their answer to the question, "Have you returned to the
      same level of sports as before your injury?" Group differences in demographics,
      knee impairments, and self-report questionnaire responses were analyzed.
      Discriminant function analysis determined the strongest predictors of group
      classification. Receiver-operating-characteristic curves determined the
      discriminatory accuracy of the identified clinical variables. RESULTS: Fifty-two
      of 94 patients (55%) reported yes return to sports. Patients reporting return to
      preinjury levels of sports participation were more likely to have had less knee
      joint effusion, fewer episodes of knee instability, lower knee pain intensity,
      higher quadriceps peak torque-body weight ratio, higher score on the
      International Knee Documentation Committee Subjective Knee Evaluation Form, and
      lower levels of kinesiophobia. Knee joint effusion, episodes of knee instability,
      and score on the International Knee Documentation Committee Subjective Knee
      Evaluation Form were identified as the factors most strongly associated with self
      reported return-to-sport status. The highest positive likelihood ratio for the
      yes-return-to-sports group classification (14.54) was achieved when patients met
      all of the following criteria: no knee effusion, no episodes of instability, and
      International Knee Documentation Committee Subjective Knee Evaluation Form score
      greater than 93. CONCLUSION: In multivariate analysis, the factors most strongly
      associated with return-to-sport status included only self-reported knee function,
      episodes of knee instability, and knee joint effusion.

PMID- 22951438
TI  - Fluid biomarkers in Alzheimer disease.
AB  - Research progress has provided detailed understanding of the molecular
      pathogenesis of Alzheimer disease (AD). This knowledge has been translated into
      new drug candidates with putative disease-modifying effects, which are now being
      tested in clinical trials. The promise of effective therapy has created a great
      need for biomarkers able to detect AD in the predementia phase, because drugs
      will probably be effective only if neurodegeneration is not too advanced. In this
      chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core
      CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino
      acid form of beta-amyloid (Abeta42) reflect AD pathology, and have high
      diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild
      cognitive impairment cases. The rationale for the use of CSF biomarkers to
      identify and monitor the mechanism of action of new drug candidates is also
      outlined in this chapter.

PMID- 22951440
TI  - VEGF-directed blood vessel patterning: from cells to organism.
AB  - VEGF-A signaling is required for almost every aspect of vascular development, and
      it is a major regulator of vessel morphogenesis and patterning. VEGF-A
      perturbations are associated with severe vascular defects and lethality, and the
      pathway is coopted in pathological scenarios, including tumor angiogenesis. This
      review focuses on the roles of VEGF-A signaling during vessel development and
      patterning. I review the impact of VEGF-A signaling on endothelial cells in
      developing vessels, with emphasis on the importance of spatial regulation of
      several pathway components. I also discuss VEGF-A signaling patterns at the level
      of the vessel, with a focus on how polarity is set up and maintained in several
      vessel axes. The role of VEGF-A in patterning vessels relative to tissues and
      organs is also reviewed, with emphasis on neurovascular patterning and patterning
      at the embryonic midline.

PMID- 22951439
TI  - Treatment strategies targeting amyloid beta-protein.
AB  - With the advent of the key discovery in the mid-1980s that the amyloid beta
      protein (Abeta) is the core constituent of the amyloid plaque pathology found in
      Alzheimer disease (AD), an intensive effort has been underway to attempt to
      mitigate its role in the hope of treating the disease. This effort fully matured
      when it was clarified that the Abeta is a normal product of cleavage of the
      amyloid precursor protein, and well-defined proteases for this process were
      identified. Further therapeutic options have been developed around the concept of
      anti-Abeta aggregation inhibitors and the surprising finding that immunization
      with Abeta itself leads to reduction of pathology in animal models of the
      disease. Here we review the progress in this field toward the goal of targeting
      Abeta for treatment and prevention of AD and identify some of the major
      challenges for the future of this area of medicine.

PMID- 22951441
TI  - The complex role of angiopoietin-2 in the angiopoietin-tie signaling pathway.
AB  - The angiopoietin-Tie signaling system is a vascular-specific receptor tyrosine
      kinase pathway that is essential for normal vascular development. Although the
      basic functioning of the pathway is understood, many uncertainties remain about
      the role of certain members of the pathway, particularly angiopoietin-2 (Ang2),
      in pathological vascular remodeling and angiogenesis. We summarize the components
      of the angiopoietin-Tie pathway and then focus on studies that highlight the role
      of Ang2 in disease settings, including cancer and inflammation. The expression of
      Ang2 is elevated in many cancers and types of inflammation, which prompted the
      development of specific reagents to block its interaction with the Tie2 receptor.
      The application of these reagents in preclinical models of inflammation and
      cancer has begun to elucidate the role of Ang2 in vascular remodeling and disease
      pathogenesis and has led to emerging clinical tests of Ang2 inhibitors.

PMID- 22951443
TI  - Endoplasmic reticulum stress, pancreatic beta-cell degeneration, and diabetes.
AB  - Overwhelming of protein folding in the endoplasmic reticulum (ER)--referred to as
      "ER stress"--activates a set of intracellular signaling pathways termed the
      unfolded protein response (UPR). Beneficial outputs of the UPR promote adaptation
      in cells experiencing manageably low levels of ER stress. However, if ER stress
      reaches critically high levels, the UPR uses destructive outputs to trigger
      programmed cell death. Genetic mutations in various UPR components cause
      inherited syndromes of diabetes mellitus in both rodents and humans, implicating
      the UPR in the proper functioning and survival of pancreatic islet beta cells.
      Markers of chronically elevated ER stress, terminal UPR signaling, and apoptosis
      are evident in beta cells in these rare disorders; these markers are similarly
      present in islets of human patients with common forms of diabetes. These findings
      promise to enhance our molecular understanding of human diabetes significantly
      and may lead to new and effective therapies.

PMID- 22951442
TI  - HIV pathogenesis: the host.
AB  - Human immunodeficiency virus (HIV) pathogenesis has proven to be quite complex
      and dynamic with most of the critical events (e.g., transmission, CD4(+) T-cell
      destruction) occurring in mucosal tissues. In addition, although the resulting
      disease can progress over years, it is clear that many critical events happen
      within the first few weeks of infection when most patients are unaware that they
      are infected. These events occur predominantly in tissues other than the
      peripheral blood, particularly the gastrointestinal tract, where massive
      depletion of CD4(+) T cells occurs long before adverse consequences of HIV
      infection are otherwise apparent. Profound insights into these early events have
      been gained through the use of nonhuman primate models, which offer the
      opportunity to examine the early stages of infection with the simian
      immunodeficiency virus (SIV), a close relative of HIV that induces an
      indistinguishable clinical picture from AIDS in Asian primate species, but
      importantly, fails to cause disease in its natural African hosts, such as sooty
      mangabeys and African green monkeys. This article draws from data derived from
      both human and nonhuman primate studies.

PMID- 22951444
TI  - Do MHCII-presented neoantigens drive type 1 diabetes and other autoimmune
      diseases?
AB  - The strong association between particular MHCII alleles and type 1 diabetes is
      not fully understood. Two ideas that have been considered for many years are that
      autoimmunity is driven by (1) low-affinity CD4(+) T cells that escape thymic
      negative selection and respond to certain autoantigen peptides that are
      particularly well presented by particular MHCII molecules, or (2) CD4(+) T cells
      responding to neoantigens that are absent in the thymus, but uniquely created in
      the target tissue in the periphery and presented by particular MHCII alleles.
      Here we discuss the recent structural data in favor of the second idea. We review
      studies suggesting that peptide antigens recognized by autoimmune T cells are
      uniquely proteolytically processed and/or posttranslationally modified in the
      target tissue, thus allowing these T cells to escape deletion in the thymus
      during T-cell development. We postulate that an encounter with these tissue
      specific neoantigenic peptides presented by the particular susceptible MHCII
      alleles in the peripheral tissues when accompanied by the appropriate
      inflammatory milieu activates these T-cell escapees leading to the onset of
      autoimmune disease.

PMID- 22951445
TI  - Innate inflammation in Parkinson's disease.
AB  - The resident macrophages of the brain--the microglia--are morphologically
      activated during the progression of Parkinson's disease. Observational studies in
      human postmortem material and studies in animal models seek to define the
      contribution that this innate immune response might make to the pathogenesis and
      rate of progression of Parkinson's disease. We review here some of the key
      conceptual issues that need to be considered when performing these studies. We
      highlight the fact that most postmortem studies have not given due consideration
      to common comorbidities present in patients with Parkinson's disease and also the
      limitations of attempting to extrapolate from animal models to a chronic
      progressive neurodegenerative disease in humans that lasts for many years.

PMID- 22951446
TI  - Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and
      mitochondrial pathways.
AB  - Three genes have been identified that cause, in humans, autosomally inherited
      parkinsonism. These are PARK2, encoding the E3 ubiquitin ligase parkin; PINK1, a
      mitochondrial kinase; and PARK7, which codes for the protein DJ-1. In several
      experimental systems, it has been shown that all three proteins impact
      mitochondrial function and/or oxidative stress responses. These are probably
      related because mitochondria produce oxidative stress in neurons. Moreover, it is
      clear that there are relationships between these genes, with a single pathway
      linking PINK1 and parkin and a parallel relationship with DJ-1. Work in progress
      in the field is aimed at understanding these relationships in more depth.

PMID- 22951448
TI  - World distribution, population genetics, and health burden of the
      hemoglobinopathies.
AB  - Although information about the precise world distribution and frequency of the
      inherited hemoglobin disorders is still limited, there is no doubt that they are
      going to pose an increasing burden on global health resources in the future.
      Their high frequency is a reflection of natural selection combined with a high
      frequency of consanguineous marriages in many countries, together with an
      epidemiological transition; whereby, as public health measures improve in the
      poorer countries of the world, more babies with these disorders are surviving to
      present for treatment.

PMID- 22951450
TI  - National, state, and local area vaccination coverage among children aged 19-35
      months--United States, 2011.
AB  - High vaccination coverage in children by age 2 years has resulted in historically
      low levels of most vaccine-preventable diseases in the United States, but
      coverage must be maintained to reduce the burden of disease further and prevent a
      resurgence of these diseases, particularly in populations with lower vaccination
      coverage. This report describes national, state, and selected local area
      vaccination coverage by age 19-35 months for children born during January 2008
      May 2010, based on 2011 National Immunization Survey (NIS) results. Vaccination
      coverage remained above the national Healthy People 2020 target* of 90% for >=1
      dose measles, mumps, rubella vaccine (MMR) (91.6%), >=3 doses of hepatitis B
      vaccine (HepB) (91.1%), >=3 doses of poliovirus vaccine (93.9%), and >=1 dose of
      varicella vaccine (90.8%). For the birth dose of HepB, coverage increased from
      64.1% in 2010 to 68.6% in 2011; for the more recently recommended >=2 doses of
      hepatitis A vaccine (HepA) and rotavirus vaccines, coverage increased from 49.7%
      to 52.2% and from 59.2% to 67.3%, respectively; and for the full series of
      Haemophilus influenzae type b vaccine (Hib), coverage increased from 66.8% to
      80.4%, reflecting recovery from the Hib shortage that occurred during December
      2007-September 2009. The percentage of children who had not received any
      vaccinations remained at <1%. Children living below the poverty level had lower
      coverage than children living at or above poverty for >=4 doses of diphtheria,
      tetanus toxoid, and acellular pertussis vaccine (DTaP) and >=4 doses of
      pneumococcal conjugate vaccine (PCV) (by 6 percentage points each); the full Hib
      series (by 8 percentage points); and for rotavirus vaccination (by 10 percentage
      points). Continued partnerships among national, state, local, private, and public
      entities are needed to sustain current coverage levels and ensure that coverage
      for the more recently recommended vaccines continues to increase for all
      children.

PMID- 22951451
TI  - Prevalence of cholesterol screening and high blood cholesterol among adults-
      United States, 2005, 2007, and 2009.
AB  - High blood cholesterol is a leading risk factor in the development of
      atherosclerosis and coronary heart disease (CHD). The risks associated with high
      blood cholesterol can be reduced by screening and early intervention. Current
      clinical practice guidelines provide evidenced-based standards for detection,
      treatment, and control of high blood cholesterol. Healthy People 2020 monitors
      national progress related to screening and controlling high blood cholesterol
      through the National Health Interview Survey and the National Health and
      Nutrition Examination Survey (NHANES). State-level estimates of self-reported
      cholesterol screening and high blood cholesterol prevalence are available using
      Behavioral Risk Factor Surveillance System (BRFSS) data. To assess recent trends
      in the percentage of adults aged >=18 years who had been screened for high blood
      cholesterol during the preceding 5 years, and the percentage among those who had
      been screened within the previous 5 years and who were ever told they had high
      blood cholesterol, CDC analyzed BRFSS data from 2005, 2007, and 2009. The results
      of that analysis showed that the percentage of adults reporting having been
      screened for high blood cholesterol within the preceding 5 years increased
      overall from 72.7% in 2005 to 76.0% in 2009. In addition, the percentage who had
      ever been told they had high cholesterol increased from 33.2% to 35.0%. Both self
      reported screening and high cholesterol varied by state and sociodemographic
      subgroup. To reach the Healthy People 2020 target for cholesterol screening,
      public health practitioners should emphasize the importance of screening,
      especially among younger adults, men, Hispanics, and persons with lower levels of
      education.

PMID- 22951449
TI  - Glutamate mechanisms underlying opiate memories.
AB  - As the major excitatory neurotransmitter in the brain, glutamate plays an
      undisputable integral role in opiate addiction. This relates, in part, to the
      fact that addiction is a disorder of learning and memory, and glutamate is
      required for most types of memory formation. As opiate addiction develops, the
      addict becomes conditioned to engage in addictive behaviors, and these behaviors
      can be triggered by opiate-associated cues during abstinence, resulting in
      relapse. Some medications for opiate addiction exert their therapeutic effects at
      glutamate receptors, especially the NMDA receptor. Understanding the neural
      circuits controlling opiate addiction, and the locus of glutamate's actions
      within these circuits, will help guide the development of targeted
      pharmacotherapeutics for relapse.

PMID- 22951452
TI  - Vital signs: awareness and treatment of uncontrolled hypertension among adults-
      United States, 2003-2010.
AB  - BACKGROUND: Hypertension is a leading risk factor for cardiovascular disease and
      a significant cause of morbidity and mortality. This report uses data from the
      National Health and Nutrition Examination Survey (NHANES) to examine awareness
      and pharmacologic treatment of uncontrolled hypertension among U.S. adults with
      hypertension and focuses on three groups: those who are unaware of their
      hypertension, those who are aware but not treated with medication, and those who
      are aware and pharmacologically treated with medication but still have
      uncontrolled hypertension. METHODS: CDC analyzed data from the NHANES 2003-2010
      to estimate the prevalence of hypertension awareness and treatment among adults
      with uncontrolled hypertension. Hypertension was defined as an average systolic
      blood pressure (SBP)>=140 mmHg or an average diastolic blood pressure (DBP)>=90
      mmHg, or currently using blood pressure (BP)-lowering medication. Uncontrolled
      hypertension was defined as an average SBP>=140 mmHg or an average DBP>=90 mmHg,
      among those with hypertension. RESULTS: The overall prevalence of hypertension
      among U.S. adults aged>=18 years in 2003-2010 was 30.4% or an estimated 66.9
      million. Among those with hypertension, an estimated 35.8 million (53.5%) did not
      have their hypertension controlled. Among these, an estimated 14.1 million
      (39.4%) were not aware of their hypertension, an estimated 5.7 million (15.8%)
      were aware of their hypertension but were not receiving pharmacologic treatment,
      and an estimated 16.0 million (44.8%) were aware of their hypertension and were
      being treated with medication. Of the 35.8 million U.S. adults with uncontrolled
      hypertension, 89.4% reported having a usual source of health care, and 85.2%
      reported having health insurance. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Nearly
      90% of U.S. adults with uncontrolled hypertension have a usual source of health
      care and insurance, representing a missed opportunity for hypertension control.
      Improved hypertension control will require an expanded effort and an increased
      focus on BP from health-care systems, clinicians, and individuals.

PMID- 22951447
TI  - CFTR, mucins, and mucus obstruction in cystic fibrosis.
AB  - Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease
      has been recognized and is sometimes called mucoviscidosis. The disease is marked
      by mucus hyperproduction and plugging in many organs, which are usually most
      fatal in the airways of CF patients, once the problem of meconium ileus at birth
      is resolved. After the CF gene, CFTR, was cloned and its protein product
      identified as a cAMP-regulated Cl(-) channel, causal mechanisms underlying the
      strong mucus phenotype of the disease became obscure. Here we focus on mucin
      genes and polymeric mucin glycoproteins, examining their regulation and potential
      relationships to a dysfunctional cystic fibrosis transmembrane conductance
      regulator (CFTR). Detailed examination of CFTR expression in organs and different
      cell types indicates that changes in CFTR expression do not always correlate with
      the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction
      that typifies CF does not appear to be a direct cause of a defective CFTR but,
      rather, to be a downstream consequence. In organs like the lung, up-regulation of
      mucin gene expression by inflammation results from chronic infection; however, in
      other instances and organs, the inflammation may have a non-infectious origin.
      The mucus plugging phenotype of the beta-subunit of the epithelial Na(+) channel
      (betaENaC)-overexpressing mouse is proving to be an archetypal example of this
      kind of inflammation, with a dehydrated airway surface/concentrated mucus gel
      apparently providing the inflammatory stimulus. Data indicate that the luminal
      HCO(3)(-) deficiency recently described for CF epithelia may also provide such a
      stimulus, perhaps by causing a mal-maturation of mucins as they are released onto
      luminal surfaces. In any event, the path between CFTR dysfunction and mucus
      hyperproduction has proven tortuous, and its unraveling continues to offer its
      own twists and turns, along with fascinating glimpses into biology.

PMID- 22951453
TI  - RPE65 gene therapy slows cone loss in Rpe65-deficient dogs.
AB  - Recent clinical trials of retinal pigment epithelium gene (RPE65) supplementation
      therapy in Leber congenital amaurosis type 2 patients have demonstrated
      improvements in rod and cone function, but it may be some years before the
      effects of therapy on photoreceptor survival become apparent. The Rpe65-deficient
      dog is a very useful pre-clinical model in which to test efficacy of therapies,
      because the dog has a retina with a high degree of similarity to that of humans.
      In this study, we evaluated the effect of RPE65 gene therapy on photoreceptor
      survival in order to predict the potential benefit and limitations of therapy in
      patients. We examined the retinas of Rpe65-deficient dogs after RPE65 gene
      therapy to evaluate the preservation of rods and cone photoreceptor subtypes. We
      found that gene therapy preserves both rods and cones. While the moderate loss of
      rods in the Rpe65-deficient dog retina is slowed by gene therapy, S-cones are
      lost extensively and gene therapy can prevent that loss, although only within the
      treated area. Although LM-cones are not lost extensively, cone opsin
      mislocalization indicates that they are stressed, and this can be partially
      reversed by gene therapy. Our results suggest that gene therapy may be able to
      slow cone degeneration in patients if intervention is sufficiently early and also
      that it is probably important to treat the macula in order to preserve central
      function.

PMID- 22951454
TI  - Transcriptional targeting of DCs with lentiviral vectors induces antigen-specific
      tolerance in a mouse model of multiple sclerosis.
AB  - The aim of this work was to induce permanent tolerance toward self-antigens
      involved in autoimmune diseases, such as multiple sclerosis (MS). We hypothesized
      that the stable auto-antigen presentation by dendritic cells (DCs) would tolerize
      auto-reactive T cells and, therefore, prevent disease development in a mouse
      model of experimental autoimmune encephalomyelitis (EAE), which closely resembles
      MS. Specifically, our strategy included the ex vivo modification of hematopoietic
      stem cells (HSCs) with self-inactivating (SIN) lentivirus vectors that
      transcriptionally target the expression of myelin antigens to DCs. As SIN
      lentivirus vectors support the genomic integration of transgene sequences in HSC,
      the transduced and transplanted HSC may provide a constant supply of antigen
      expressing steady-state DCs. Here, we demonstrate that targeting myelin
      oligodendrocyte glycoprotein (MOG) expression to DCs indeed resulted in complete
      and stable protection from EAE. No histological signs of EAE, such as
      demyelination, axonal damage, or infiltration of leukocytes in brain, spinal cord
      and optical nerve, were observed in tolerized mice. Tolerance induction was
      concomitant with the efficient deletion of MOG-specific T cells and the
      generation of Foxp3(+) regulatory T cells and, most importantly, directed toward
      a specific self-antigen while T-cell reactivity to unrelated foreign antigens was
      fully preserved.

PMID- 22951455
TI  - Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic
      acid-g-chitosan oligosaccharide micelles.
AB  - Non-viral vesicle composing of low-molecular weight polyethylenimine-conjugated
      stearic acid-g-chitosan oligosaccharide (CSOSA-g-PEI) was synthesized for gene
      delivery and therapy. The synthesized CSOSA-g-PEI had good ion-buffer
      capabilities and DNA-binding capacity, which could form positively charged nano
      sized particles (100-150 nm) with plasmid DNA; in vitro gene transfection tests
      demonstrated that CSOSA-g-PEI presented much lower cytotoxicity and corresponding
      transfection efficiency in comparison with Lipofectamine 2000 in both human
      cancer cells (Hela and MCF-7). The gene transfection of CSOSA-g-PEI/pDNA could be
      further enhanced in the presence of serum or by adding arginine during incubation
      of CSOSA-g-PEI micelles with plasmid DNA. The biodistribution experiments
      demonstrated CSOSA-g-PEI conjugate highly localized in the tumor tissue and
      indicated a persistently increased accumulation. In vivo antitumor activity
      results showed that CSOSA-g-PEI/plasmid pigment epithelium-derived factor
      formulation could effectively suppress the tumor growth (above 60% tumor
      inhibition) without systematic toxicity against animal body after intravenous
      injection.

PMID- 22951456
TI  - A new model for companion-animal primary health care education.
AB  - The majority of graduates from veterinary schools in the United States and Canada
      join companion-animal practices. In most schools, their clinical learning and
      client interaction experiences occurred primarily in referral teaching hospitals.
      These specialty hospitals play an essential role in the veterinary care continuum
      by providing advanced training, clinically-based research, and sophisticated
      diagnostics and procedures. However, they are not ideal as the principal setting
      for preparing veterinarians to bring value to the primary health care practices
      that they join. A new model for companion-animal primary health care education
      and service delivery has been developed at the Ontario Veterinary College,
      University of Guelph. The nine integrated programs, which have defined learning
      objectives and outcome assessments, include communication, nutrition,
      rehabilitation, behavior, welfare, One Health (ecosystem approach to health),
      preventive and general medicine, good citizenship, and research. The learning
      experience begins with first-year student veterinarians and takes place in a
      practice setting with paying clients from the community. Significantly, the
      students are learning in an environment that emphasizes the importance of the
      client experience, teamwork, and practice management while ensuring quality
      health care for patients. The future of companion-animal primary health care and
      the optimal preparation of veterinarians are critical issues for the veterinary
      colleges and profession. Enhanced research into new models for primary health
      care education and service delivery is urgently needed.

PMID- 22951457
TI  - Coaching and feedback: enhancing communication teaching and learning in
      veterinary practice settings.
AB  - Communication is a critical clinical skill closely linked to clinical reasoning,
      medical problem solving, and significant outcomes of care such as accuracy,
      efficiency, supportiveness, adherence to treatment plans, and client and
      veterinarian satisfaction. More than 40 years of research on communication and
      communication education in human medicine and, more recently, in veterinary
      medicine provide a substantive rationale for formal communication teaching in
      veterinary education. As a result, veterinary schools are beginning to invest in
      communication training. However, if communication training is to result in
      development of veterinary communication skills to a professional level of
      competence, there must be follow-through with effective communication modeling
      and coaching in practice settings. The purpose of this article is to move the
      communication modeling and coaching done in the "real world" of clinical practice
      to the next level. The development of skills for communication coaching and
      feedback is demanding. We begin by comparing communication coaching with what is
      required for teaching other clinical skills in practice settings. Examining both,
      what it takes to teach others (whether DVM students or veterinarians in practice
      for several years) and what it takes to enhance one's own communication skills
      and capacities, we consider the why, what, and how of communication coaching. We
      describe the use of teaching instruments to structure this work and give
      particular attention to how to engage in feedback sessions, since these elements
      are so critical in communication teaching and learning. We consider the
      preconditions necessary to initiate and sustain communication skills training in
      practice, including the need for a safe and supportive environment within which
      to implement communication coaching and feedback. Finally we discuss the
      challenges and opportunities unique to coaching and to building and delivering
      communication skills training in practice settings.

PMID- 22951458
TI  - Workplace-based assessment in a primary-care setting.
AB  - Workplace-based assessment (WBA) is the process of directly observing students'
      work within a clinical setting, assessing their performance, and providing
      specific, goal oriented feedback. Assessment methods used for workplace-based
      assessment include tools developed for clinical interaction (e.g., the mini
      clinical evaluation exercise [mini-CEX]), for procedural or technical skills
      (e.g., the direct observation of procedural skills [DOPS]), and multi-source
      feedback tools to assess interpersonal and technical skills. While several of
      these assessment methods are being adopted by veterinary schools to evaluate
      students' progress through their clinical rotations, there is little reported at
      this time about their utility and effectiveness within the veterinary context.
      This article provides an introduction to the use of these tools and offers
      guidance in selecting appropriate methods for assessment in the primary health
      care setting.

PMID- 22951459
TI  - Education and earnings in the health professions.

PMID- 22951460
TI  - Preparing students for careers in food-supply veterinary medicine: a review of
      educational programs in the United States.
AB  - The real and/or perceived shortage of veterinarians serving food-supply
      veterinary medicine has been a topic of considerable discussion for decades.
      Regardless of this debate, there are issues still facing colleges of veterinary
      medicine (CVMs) about the best process of educating future food-supply
      veterinarians. Over the past several years, there have been increasing concerns
      by some that the needs of food-supply veterinary medicine have not adequately
      been met through veterinary educational institutions. The food-supply veterinary
      medical curriculum offered by individual CVMs varies depending on individual
      curricular design, available resident animal population, available food-animal
      caseload, faculty, and individual teaching efforts of faculty. All of the
      institutional members of the Association of American Veterinary Medical Colleges
      (AAVMC) were requested to share their Food Animal Veterinary Career Incentives
      Programs. The AAVMC asked all member institutions what incentives they used to
      attract and educate students interested in, or possibly considering, a career in
      food-supply veterinary medicine (FSVM). The problem arises as to how we continue
      to educate veterinary students with ever shrinking budgets and how to recruit and
      retain faculty with expertise to address the needs of society. Several CVMs use
      innovative training initiatives to help build successful FSVM programs. This
      article focuses on dairy, beef, and swine food-animal education and does not
      characterize colleges' educational efforts in poultry and aquaculture. This
      review highlights the individual strategies used by the CVMs in the United
      States.

PMID- 22951461
TI  - Attributes of clinical role models as described by senior veterinary students in
      Australia.
AB  - Role models incite admiration and provide inspiration, contributing to learning
      as students aspire to emulate their example. The attributes of physician role
      models for medical trainees are well documented, but they remain largely
      unexplored in the context of veterinary medical training. The aim of the current
      study was to describe the attributes that final-year veterinary students (N=213)
      at the University of Queensland identified when reflecting on their clinical role
      models. Clinical role model descriptions provided by students were analyzed using
      concept-mapping software (Leximancer v. 2.25). The most frequent and highly
      connected concepts used by students when describing their role model(s) included
      clients, vet, and animal. Role models were described as good communicators who
      were skilled at managing relationships with clients, patients, and staff. They
      had exemplary knowledge, skills, and abilities, and they were methodical and
      conducted well-structured consultations. They were well respected and, in turn,
      demonstrated respect for clients, colleagues, staff, and students alike. They
      were also good teachers and able to tailor explanations to suit both clients and
      students. Findings from this study may serve to assist with faculty development
      and as a basis for further research in this area.

PMID- 22951462
TI  - Use of the script concordance approach to evaluate clinical reasoning in food
      ruminant practitioners.
AB  - A script concordance test (SCT) was developed measuring clinical reasoning of
      food-ruminant practitioners for whom potential clinical competence difficulties
      were identified by their provincial professional organization. The SCT was
      designed to be used as part of a broader evaluation procedure. A scoring key was
      developed based on answers from a reference panel of 12 experts and using the
      modified aggregate method commonly used for SCTs. A convenient sample of 29 food
      ruminant practitioners was constituted to assess the reliability and precision of
      the SCT and to determine a fair threshold value for success. Cronbach's alpha
      coefficients were computed to evaluate internal reliability. To evaluate SCT
      precision, a test-retest methodology was used and measures of agreement beyond
      chance were computed at question and test levels. After optimization, the 36
      question SCT yielded acceptable internal reliability (Cronbach's alpha=0.70).
      Precision of the SCT at question level was excellent with 33 questions (92%)
      yielding moderate to almost perfect agreement between administrations. At test
      level, fair agreement (concordance correlation coefficient=0.32) was observed
      between administrations. A slight SCT score improvement (M=+2.8 points) on the
      second administration was in part responsible for some of the disagreement and
      was potentially a result of an adaptation to the SCT format. Scores distribution
      was used to determine a fair threshold value for success, while considering the
      underlying objectives of the examination. The data suggest that the developed SCT
      can be used as a reliable and precise measurement of clinical reasoning of food
      ruminant practitioners.

PMID- 22951463
TI  - Validation of a scenario-based assessment of critical thinking using an
      externally validated tool.
AB  - With medical education transitioning from knowledge-based curricula to competency
      based curricula, critical thinking skills have emerged as a major competency.
      While there are validated external instruments for assessing critical thinking,
      many educators have created their own custom assessments of critical thinking.
      However, the face validity of these assessments has not been challenged. The
      purpose of this study was to compare results from a custom assessment of critical
      thinking with the results from a validated external instrument of critical
      thinking. Students from the College of Veterinary Medicine at Western University
      of Health Sciences were administered a custom assessment of critical thinking
      (ACT) examination and the externally validated instrument, California Critical
      Thinking Skills Test (CCTST), in the spring of 2011. Total scores and sub-scores
      from each exam were analyzed for significant correlations using Pearson
      correlation coefficients. Significant correlations between ACT Blooms 2 and
      deductive reasoning and total ACT score and deductive reasoning were demonstrated
      with correlation coefficients of 0.24 and 0.22, respectively. No other
      statistically significant correlations were found. The lack of significant
      correlation between the two examinations illustrates the need in medical
      education to externally validate internal custom assessments. Ultimately, the
      development and validation of custom assessments of non-knowledge-based
      competencies will produce higher quality medical professionals.

PMID- 22951464
TI  - Can online conference systems improve veterinary education? A study about the
      capability of online conferencing and its acceptance.
AB  - In veterinary medicine, there is an ongoing need for students, educators, and
      veterinarians to exchange the latest knowledge in their respective fields and to
      learn about unusual cases, emerging diseases, and treatment. Networking among
      veterinary faculties is developing rapidly, but conferences and meetings can be
      difficult to attend because of time limitations and travel costs. The current
      study examines acceptance of synchronous online conferences, seminars, meetings,
      and lectures by veterinarians and students. First, an online survey on the use of
      communication technology in veterinary medicine was made available for 15 weeks
      to every German-speaking veterinary university and via professional journals and
      an online veterinary forum. A total of 1,776 persons (620 veterinarians and 1,156
      students) participated. Most reported using the Internet at least once per day;
      more than half reported using instant messengers. Most participants used the
      Internet for communication, but less than half used Skype. Second, to test the
      spectrum of tools for online conferences, a variety of "virtual classroom"
      systems (netucate systems iLinc, Adobe Acrobat Connect Pro, Cisco WebEx, Skype)
      were used to deliver student lectures, veterinary continuing-education courses,
      and academic conferences at the University of Veterinary Medicine, Hannover
      (TiHo). Of 591 participants in 63 online events, 99.4% rated the virtual events
      as enjoyable, 96.1% found them useful, and 92.4% said that they learned a lot.
      Participants noted that the courses were not tied to a certain place, and thus
      saved time and travel costs. Online conference systems thus offer new
      opportunities to provide information in veterinary medicine.

PMID- 22951465
TI  - Understanding veterinary students' use of and attitudes toward the social
      networking site, Facebook, to assist in developing curricula to address online
      professionalism.
AB  - Social media is an increasingly common form of communication, with Facebook being
      the preferred social-networking site among post-secondary students. Numerous
      studies suggest post-secondary students practice high self-disclosure on
      Facebook. Research evaluating veterinary students' use of social media found a
      notable proportion of student-posted content deemed inappropriate. Lack of
      discretion in posting content can have significant repercussions for aspiring
      veterinary professionals, their college of study, and the veterinary profession
      they represent. Veterinarians-in-training at three veterinary colleges across
      Canada were surveyed to explore their use of and attitude toward the social
      networking site, Facebook. Students were invited to complete an online survey
      with questions relating to their knowledge of privacy in relation to using
      Facebook, their views on the acceptability of posting certain types of
      information, and their level of professional accountability online. Linear
      regression modeling was used to further examine factors related to veterinary
      students' disclosure of personal information on Facebook. Need for popularity
      (p<.01) and awareness of consequences (p<.001) were found to be positively and
      negatively associated, respectively, with students' personal disclosure of
      information on Facebook. Understanding veterinary students' use of and attitudes
      toward social media, such as Facebook, reveals a need, and provides a basis, for
      developing educational programs to address online professionalism. Educators and
      administrators at veterinary schools may use this information to assist in
      developing veterinary curricula that addresses the escalating issue of online
      professionalism.

PMID- 22951466
TI  - Assessment of first-year veterinary students' communication skills using an
      objective structured clinical examination: the importance of context.
AB  - Communication skills are considered to be a core clinical skill in veterinary
      medicine and essential for practice success, including outcomes of care for
      patients and clients. While veterinary schools include communication skills
      training in their programs, there is minimal knowledge on how best to assess
      communication competence throughout the undergraduate program. The purpose of
      this study was to further our understanding of the reliability, utility, and
      suitability of a communication skills Objective Structured Clinical Examination
      (OSCE). Specifically we wanted to (1) identify the greatest source of variability
      (student, rater, station, and track) within a first-year, four station OSCE using
      exam scores and scores from videotape review by two trained raters, and (2)
      determine the effect of different stations on students' communication skills
      performance. Reliability of the scores from both the exam data and the two expert
      raters was 0.50 and 0.46 respectively, with the greatest amount of variance
      attributable to student by station. The percentage of variance due to raters in
      the exam data was 16.35%, whereas the percentage of variance for the two expert
      raters was 0%. These results have three important implications. First, the
      results reinforce the need for communication educators to emphasize that use of
      communication skills is moderated by the context of the clinical interaction.
      Second, by increasing rater training the amount of error in the scores due to
      raters can be reduced and inter-rater reliability increases. Third, the
      communication assessment method (in this case the OSCE checklist) should be built
      purposefully, taking into consideration the context of the case.

PMID- 22951467
TI  - Imaging calcium responses in GFP-tagged neurons of hypothalamic mouse brain
      slices.
AB  - Despite an enormous increase in our knowledge about the mechanisms underlying the
      encoding of information in the brain, a central question concerning the precise
      molecular steps as well as the activity of specific neurons in multi-functional
      nuclei of brain areas such as the hypothalamus remain. This problem includes
      identification of the molecular components involved in the regulation of various
      neurohormone signal transduction cascades. Elevations of intracellular Ca(2+)
      play an important role in regulating the sensitivity of neurons, both at the
      level of signal transduction and at synaptic sites. New tools have emerged to
      help identify neurons in the myriad of brain neurons by expressing green
      fluorescent protein (GFP) under the control of a particular promoter. To monitor
      both spatially and temporally stimulus-induced Ca(2+) responses in GFP-tagged
      neurons, a non-green fluorescent Ca(2+) indicator dye needs to be used. In
      addition, confocal microscopy is a favorite method of imaging individual neurons
      in tissue slices due to its ability to visualize neurons in distinct planes of
      depth within the tissue and to limit out-of-focus fluorescence. The ratiometric
      Ca(2+) indicator fura-2 has been used in combination with GFP-tagged neurons.
      However, the dye is excited by ultraviolet (UV) light. The cost of the laser and
      the limited optical penetration depth of UV light hindered its use in many
      laboratories. Moreover, GFP fluorescence may interfere with the fura-2 signals.
      Therefore, we decided to use a red fluorescent Ca(2+) indicator dye. The huge
      Stokes [corrected] shift of fura-red permits multicolor analysis of the red
      fluorescence in combination with GFP using a single excitation wavelength. We had
      previously good results using fura-red in combination with GFP-tagged olfactory
      neurons. The protocols for olfactory tissue slices seemed to work equally well in
      hypothalamic neurons. Fura-red based Ca(2+) imaging was also successfully
      combined with GFP-tagged pancreatic beta-cells and GFP-tagged receptors expressed
      in HEK cells. A little quirk of fura-red is that its fluorescence intensity at
      650 nm decreases once the indicator binds calcium. Therefore, the fluorescence of
      resting neurons with low Ca(2+) concentration has relatively high intensity. It
      should be noted, that other red Ca(2+)-indicator dyes exist or are currently
      being developed, that might give better or improved results in different neurons
      and brain areas.

PMID- 22951468
TI  - Influence of the antiandrogen flutamide on the androgen receptor gene expression
      in the placenta and umbilical cord during pregnancy in the pig.
AB  - The aim of this study was to determine the immunolocalization and expression of
      the androgen receptor (AR) in the pig placenta and umbilical cord during
      pregnancy following exposure to flutamide, a non-steroidal antiandrogen, at its
      various stages. Pregnant pigs were injected with flutamide at a daily dose of
      50mg/kg body weight at different stages of pregnancy: from day 83-89 (n=2); from
      day 101-107 (n=2). They were sacrificed and tissues collected one day after the
      last injection. Control animals, two for each experimental point, were injected
      only with the vehicle (corn oil). Collected tissue samples were fixed for
      immunohistochemistry or frozen for protein isolation. AR protein was detected in
      the nucleus of trophoblast cells forming the structure of ridges and in maternal
      endothelial cells, which are involved in the placental barrier formation. It was
      also localized in the nuclei of cells forming umbilical cord components:
      allantoic duct epithelium, amniotic epithelium, Wharton's jelly and the muscular
      layer of the umbilical cord vein and arteries. Relative optical density analysis
      showed increased expression in the material derived from animals treated with
      flutamide. The presence of AR in the placental barrier and in the umbilical cord
      components suggests a role of androgen in those temporary organs. Flutamide could
      impact on the levels of the AR protein in the reproductive tracts during
      pregnancy in sows.

PMID- 22951469
TI  - Application of adipocyte-derived stem cells in treatment of cutaneous radiation
      syndrome.
AB  - Cutaneous radiation syndrome caused by local high dose irradiation is
      characterized by delayed outcome and incomplete healing. Recent therapeutic
      management of accidentally irradiated burn patients has suggested the benefit of
      local cellular therapy using mesenchymal stem cell grafting. According to the
      proposed strategy of early treatment, large amounts of stem cells would be
      necessary in the days following exposure and hospitalization, which would require
      allogeneic stem cells banking. In this context, the authors compared the benefit
      of local autologous and allogeneic adipocyte-derived stem cell injection in a
      large animal model. Minipigs were locally irradiated using a 60Co gamma source at
      a dose of 50 Gy and divided into three groups. Two groups were grafted with
      autologous (n = 5) or allogeneic (n = 5) adipocyte-derived stem cells four times
      after the radiation exposure, whereas the control group received the vehicle
      without cells (n = 8). A clinical score was elaborated to compare the efficiency
      of the three treatments. All controls exhibited local inflammatory injuries
      leading to a persistent painful necrosis, thus mimicking the clinical evolution
      in human victims. In the autologous adipocyte-derived stem cells group, skin
      healing without necrosis or uncontrollable pain was observed. In contrast, the
      clinical outcome was not significantly different in the adipocyte-derived stem
      cell allogeneic group when compared with controls. This study suggests that
      autologous adipocyte-derived stem cell grafting improves cutaneous radiation
      syndrome wound healing, whereas allogeneic adipocyte derived stem cells do not.
      Further studies will establish whether manipulation of allogeneic stem cells will
      improve their therapeutic potential.

PMID- 22951470
TI  - High potential for methodical improvements of FISH-based translocation analysis
      for retrospective radiation biodosimetry.
AB  - Due to their high stability and accumulation over time, translocations are
      currently the cytogenetic marker of choice for radiation dose estimation
      following protracted radiation overexposures or overexposures that occurred up to
      several decades in the past (environmental/occupational/medical exposures). In
      the course of this, particular intention is focused on the quantification of low
      doses (? 1.0 Gy) for the purpose of evaluating potential associations between
      different radiation-induced chromosomal aberrations and future health
      impairments, usually cancer. However, existing limitations of FISH-based
      translocation analysis give occasion to further optimize this method. In
      particular, the practical and technical aspects of the method offer a great scope
      for potential improvements considerably facilitating the performance of extensive
      studies. On the one hand, huge studies encompassing a considerable number of
      different collectives aiming at the determination of spontaneous translocation
      frequencies due to several already determined and potentially not yet known
      confounders are essential for improved individual dosimetry in the very low dose
      range. An accurate and reliable individual dosimetry and the methodical
      feasibility of extensive FISH-based studies are prerequisites to further
      elucidate the characteristics of radiation induced cancer; e.g., radiation and
      radiation quality specificity or total dose and dose rate dependencies. This
      paper focuses on the practical and technical limitations of FISH-based
      translocation analysis, in fact the tremendous workload and costs of huge
      approaches, and points out how this could be overcome by method optimization,
      namely standardizing and automating translocation scoring to allow sharing of
      future work and planning of more extensive studies.

PMID- 22951471
TI  - Gene therapy to mitigate radiation-induced bone marrow aplasia:  preliminary
      study in highly irradiated monkeys.
AB  - The hematopoietic syndrome represents the first therapeutic challenge following
      exposure to high doses of ionizing radiation. Today there is a crucial need to
      identify/develop new treatments in order to reach the transplantation threshold.
      The authors propose the concept of a global niche therapy strategy based on local
      and short-term secretion of selected morphogenes to favor a vascular niche in
      order to raise the transplantation threshold regeneration and to stimulate
      residual hematopoietic stem and progenitor cells. The present study was aimed at
      setting up a monkey model of gene therapy using Sonic hedgehog (Shh) as a first
      candidate. Multipotent mesenchymal stem cells from adipocyte tissues were
      nucleofected with mock and Sonic hedgehog pIRES2 plasmids using Amaxa technology.
      8-Gy gamma irradiated monkeys were given a single intraosseous injection of
      manipulated or unmanipulated adipocyte stem cells 48 h following total body
      irradiation. Mock and Shh-grafts were well tolerated. This preliminary study
      establishes the feasibility of transient gene therapy in highly irradiated
      monkeys. Ongoing studies will determine the putative efficacy of this therapeutic
      strategy.

PMID- 22951472
TI  - Assessment of total- and partial-body irradiation in a baboon model:  preliminary
      results of a kinetic study including clinical, physical, and biological
      parameters.
AB  - This biodosimetry study used irradiated baboons to investigate the efficacy of a
      kinetic multiparameter (clinical, physical, and biological) approach for
      discriminating partial-body irradiation (PBI) and total-body irradiation (TBI).
      Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min)
      using either TBI or vertical left hemi-body irradiation (HBI), as follows: 2.5 Gy
      TBI (n = 2), 5 Gy TBI (n = 2), 5 Gy HBI (n = 2), and 10 Gy HBI (n = 2). Midline
      tissue doses were measured at the anterior iliac crest level with an ionization
      chamber, and body dosimetry was performed using thermoluminescent dosimeters.
      Blood samples were collected before exposure and from 1 h until 200 d after
      irradiation. Clinical status, complete blood cell count, biochemical parameters,
      and cytogenetic analysis were evaluated. The partial least square discriminant
      analysis chosen for statistical analysis showed that the four groups of
      irradiated baboons were clearly separated. However, the dicentric chromosome
      assay may not distinguish HBI from TBI in confounding situations where equivalent
      whole-body doses are similar and the time of exposure is sufficient for
      peripheral blood lymphocyte homogenization. Interestingly, as bone marrow
      shielding in HBI animals prevented aplasia from happening, hematologic parameters
      such as the platelet count and Flt-3 ligand level helped to distinguish HBI and
      TBI. Moreover, the ratio of neutrophil to lymphocyte counts, creatine kinase, and
      citrulline levels may be discriminating biomarkers of dose or injury. Both early
      and delayed clinical signs and bioindicators appear to be useful for assessment
      of heterogeneous irradiation.

PMID- 22951473
TI  - Biophysics and medical effects of enhanced radiation weapons.
AB  - Enhanced radiation weapons (ERW) are fission-fusion devices where the massive
      numbers of neutrons generated during the fusion process are intentionally allowed
      to escape rather than be confined to increase yield (and fallout products). As a
      result, the energy partition of the weapon output shifts from blast and thermal
      energies toward prompt radiation. The neutron/gamma output ratio is also
      increased. Neutrons emitted from ERW are of higher energy than the Eave of
      neutrons from fission weapons. These factors affect the patterns of injury
      distribution; delay wound healing in combined injuries; reduce the therapeutic
      efficacy of medical countermeasures; and increase the dose to radiation-only
      casualties, thus potentiating the likelihood of encountering radiation-induced
      incapacitation. The risk of radiation-induced carcinogenesis is also increased.
      Radiation exposure to first responders from activation products is increased over
      that expected from a fission weapon of similar yield. However, the zone of
      dangerous fallout is significantly reduced in area. At least four nations have
      developed the potential to produce such weapons. Although the probability of
      detonation of an ERW in the near future is very small, it is nonzero, and
      clinicians and medical planners should be aware of the medical effects of ERW.

PMID- 22951474
TI  - Reliable and sample saving gene expression analysis approach for diagnostic tool
      development.
AB  - This work answers the question of whether it is necessary to hybridize individual
      instead of pooled RNA samples on microarrays for screening gene targets suitable
      as diagnostic tools for radiation exposure scenarios, while at the same time
      meeting comparable microarray quality criteria. For developing new clinical
      diagnostic tools, a two-stage study design was employed in five projects. At
      first, pooled and not individual RNA samples were hybridized on microarrays for
      screening purposes. Potential gene candidates were selected based on their fold
      change only. This was followed by a validation/quantification step using
      individual RNA samples and quantitative RT-PCR. Quality criteria from the
      screening approach with pooled RNA samples were compared with published data from
      the MicroArray Quality Control (MAQC) consortium that hybridized each reference
      RNA sample separately and established quality criteria for microarrays. When
      comparing both approaches, only insignificant differences for quality criteria
      such as false positives, sensitivity, specificity, and overall agreement were
      found. However, material, costs, and time were drastically reduced when
      hybridizing pooled RNA and gene targets applicable for clinical diagnostic
      purposes could be successfully selected. In search of new diagnostic tools for
      radiation exposure scenarios, the two stage study design using either pooled or
      individual RNA samples on microarrays shows comparable quality criteria, but the
      RNA pooling approach saves unique material, costs, and efforts and successfully
      selects gene targets that can be used for the desired diagnostic purposes.

PMID- 22951475
TI  - The Fukushima Daiichi nuclear accident--an overview.
AB  - The Fukushima Daiichi nuclear accident on 11 March 2011 was a consequence of the
      9.0 magnitude Tohoku earthquake and the following tsunami. A series of ongoing
      equipment failures in several units of the power plant led to releases of
      radioactive material into the atmosphere and the seawater. Based on these
      emissions, the accident was regarded as a level 7 (major accident) on the
      International Nuclear and Radiological Event Scale (INES). The emissions caused
      significant radiation and isotope concentrations measured in the environment by
      involved institutions. Measurements were performed on different media like soil,
      water, and foodstuffs. Based on these monitoring data, the authorities in Japan
      implemented emergency measures to protect the population of the region. These
      measures were, for example, evacuating the people from the zone where high gamma
      dose rates were detected or banning contaminated foodstuffs with respect to
      existing limit values. Direct and indirect effects of the releases in Japan could
      also be observed in Europe. However, it should be noted that the measured values
      were far below those values that could affect human health.

PMID- 22951476
TI  - Study of the stability of EPR signals after irradiation of fingernail samples.
AB  - Previous studies have suggested that the electron paramagnetic resonance in
      fingernails can be used for radiation dosimetry purposes. Use of fingernails as
      an emergency dosimeter has benefits of easy, noninvasive sampling and fast dose
      measurements (~10 min) potentially in field conditions and almost immediately
      after an exposure event. This study represents the next step in the development
      of EPR fingernail dosimetry; e.g., evaluation of the stability of the radiation
      induced signal (RIS) at different storage and irradiation conditions. RIS fading
      during storage in both stressed (untreated) and unstressed (soaked in water)
      samples (n = 20) was studied at two temperature conditions: freezing (temp ~ -20
      degrees C) and room temperature (20-24 degrees C). Fingernail samples with the
      same clipping size and number and irradiated to 15 and 20 Gy were measured for
      over 200 d. Those irradiated to 100 and 200 Gy were measured for 114 d. The other
      group of samples irradiated to 1, 3, 8, and 20 Gy was followed for 25 mo of
      storage time. This study demonstrated that all samples that were kept at low
      freezing temperatures showed a stable RIS with no significant fading. All samples
      that were kept at room temperatures showed an initial fading of the signal with a
      slow rise of the EPR signal after irradiation with time to a saturation level.
      Obtained results allow making recommendations on the appropriate storage
      conditions of fingernails for EPR dosimetry use.

PMID- 22951477
TI  - X-ray fluorescence microscopy for investigation of archival tissues.
AB  - Several recent efforts in the radiation biology community worldwide have amassed
      records and archival tissues from animals exposed to different radionuclides and
      external beam irradiation. In most cases, these samples come from lifelong
      studies on large animal populations conducted in national laboratories and
      equivalent institutions throughout Europe, North America, and Japan. While many
      of these tissues were used for histopathological analyses, much more information
      may still be obtained from these samples. A new technique suitable for imaging of
      these tissues is x-ray fluorescence microscopy (XFM). Following development of
      third generation synchrotrons, XFM has emerged as an ideal technique for the
      study of metal content, speciation, and localization in cells, tissues, and
      organs. Here the authors review some of the recent XFM literature pertinent to
      tissue sample studies and present examples of XFM data obtained from tissue
      sections of beagle dog samples, which show that the quality of archival tissues
      allows XFM investigation.

PMID- 22951478
TI  - Internal contamination by actinides after wounding:  a robust rodent model for
      assessment of local and distant actinide retention.
AB  - Internal contamination by actinides following wounding may occur in nuclear fuel
      industry workers or subsequent to terrorist activities, causing dissemination of
      radioactive elements. Contamination by alpha particle emitting actinides can
      result in pathological effects, either local or distant from the site of entry.
      The objective of the present study was to develop a robust experimental approach
      in the rat for short- and long- term actinide contamination following wounding by
      incision of the skin and muscles of the hind limb. Anesthetized rats were
      contaminated with Mixed OXide (MOX, uranium, plutonium oxides containing 7.1%
      plutonium) or plutonium nitrate (Pu nitrate) following wounding by deep incision
      of the hind leg. Actinide excretion and tissue levels were measured as well as
      histological changes from 2 h to 3 mo. Humid swabs were used for rapid evaluation
      of contamination levels and proved to be an initial guide for contamination
      levels. Although the activity transferred from wound to blood is higher after
      contamination with a moderately soluble form of plutonium (nitrate), at 7 d most
      of the MOX (98%) or Pu nitrate (87%) was retained at the wound site. Rapid
      actinide retention in liver and bone was observed within 24 h, which increased up
      to 3 mo. After MOX contamination, a more rapid initial urinary excretion of
      americium was observed compared with plutonium. At 3 mo, around 95% of activity
      remained at the wound site, and excretion of Pu and Am was extremely low. This
      experimental approach could be applied to other situations involving
      contamination following wounding including rupture of the dermal, vascular, and
      muscle barriers.

PMID- 22951479
TI  - Improved classification of evidence for EMF health risks.
AB  - Classifying evidence of causality between a risk factor and its potential health
      effect is challenging, in particular in an already emotional situation. Even the
      assessment of health risks by designated bodies may still depend on their
      composition of individuals with their background, bias, and, in worst case, their
      interests. This may explain opposing conclusions from the same pool of data
      which, consequently, may undermine credibility if not communicated properly. To
      overcome existing weakness in classifying and communicating evidence of health
      risks such as from electromagnetic fields, a new rule-based approach is
      presented. Developed by the German Commission on Radiological Protection (SSK),
      it discloses step-by-step the criteria for weighing scientific data and pools
      partial evidences of different scientific approaches to conclude on the overall
      evidence of causality between risk factor and effects. The validity of the
      approach is demonstrated by analyzing evidence of carcinogenicity of ionizing
      radiation, mobile phone use, and nocturnal exposure to visible light.

PMID- 22951480
TI  - Emergency care centers--an efficient method for mitigation of consequences after
      a dirty bomb attack.
AB  - For emergency preparedness and response with respect to nuclear power plant
      accidents, the concept of Emergency Care Centers has been developed in Germany.
      This setup aims at monitoring contamination, to decontaminate if needed, assess
      the dose, and perform an initial medical evaluation of people who might have been
      affected by the accident. The concept has been tested in many exercises. In
      response to a terrorist attack involving a dirty bomb, this concept may prove
      useful for attending contaminated people who are not severely injured.

PMID- 22951481
TI  - Thermal effusivity:  a promising imaging biomarker to predict radiation-induced
      skin injuries.
AB  - An effective screening technology is needed to triage individuals at the time of
      radiation incidents involving a large population. Three-dimensional thermal
      tomography is a relatively new development in active thermal imaging technology
      that produces cross-sectional images based on the subject's ability to transfer
      heat-thermal effusivity-at the voxel level. This noninvasive imaging modality has
      been used successfully in nondestructive examination of complex materials; also
      it has been shown to predict the severity of radiation-induced skin injuries
      several days before the manifestation of severe moist desquamations or blister
      formation symptoms in mice at 40 Gy. If these results are confirmed at lower dose
      levels in human subjects, a thermal tomography imaging device may be an ideal
      screening tool in radiation emergencies. This imaging method is non-invasive,
      relatively simple, easily adaptable for field use, and when properly deployed, it
      will enhance public emergency preparedness for incidents involving unexpected
      radiation exposure.

PMID- 22951482
TI  - Evaluation of demographic factors that influence acute radiation response.
AB  - Casualty estimation tools are critical in planning for nuclear event scenarios.
      Current consequence assessment models based on healthy adult males may not
      adequately represent the population. To develop an understanding of the impact of
      demographic variables on casualty estimates, human data was surveyed to identify
      key demographic factors that affect acute radiation response. Information on in
      utero exposures, gender, age, and comorbidity status was collected from atomic
      bomb survivors, radiation accidents, and clinical oncology. Burn and trauma
      studies were also examined to gain insight into the impact of demographic
      variables on acute injury outcomes. Fetal radiation sensitivity is well
      documented; increased mortality or malformations are observed depending on
      gestational age. A greater incidence of radiation syndrome was observed among
      male atomic bomb survivors. Trauma data show increased mortality in males,
      apparently due to immunological differences between genders. Limited data suggest
      vulnerability in the very young and old due to immunological status and
      comorbidities, respectively. Certain genetically susceptible subpopulations
      demonstrate marked increased sensitivity to radiation exposure. Interaction of
      radiation and comorbid conditions has not been well studied; however, burn and
      trauma data indicate that comorbidities negatively impact response to acute
      injury. Key factors evaluated together with their prevalence indicate the
      importance of modeling demographic variability in casualty estimations. Also they
      can help identify vulnerable subpopulations and provide insight on treatment
      requirements.

PMID- 22951483
TI  - The Fukushima radiation accident: consequences for radiation accident medical
      management.
AB  - The March 2011 radiation accident in Fukushima, Japan, is a textbook example of a
      radiation accident of global significance. In view of the global dimensions of
      the accident, it is important to consider the lessons learned. In this context,
      emphasis must be placed on consequences for planning appropriate medical
      management for radiation accidents including, for example, estimates of necessary
      human and material resources. The specific characteristics of the radiation
      accident in Fukushima are thematically divided into five groups: the exceptional
      environmental influences on the Fukushima radiation accident, particular
      circumstances of the accident, differences in risk perception, changed
      psychosocial factors in the age of the Internet and globalization, and the
      ignorance of the effects of ionizing radiation both among the general public and
      health care professionals. Conclusions like the need for reviewing international
      communication, interfacing, and interface definitions will be drawn from the
      Fukushima radiation accident.

PMID- 22951484
TI  - Quality assurance in military medical research and medical radiation accident
      management.
AB  - The provision of quality radiation-related medical diagnostic and therapeutic
      treatments cannot occur without the presence of robust quality assurance and
      standardization programs. Medical laboratory services are essential in patient
      treatment and must be able to meet the needs of all patients and the clinical
      personnel responsible for the medical care of these patients. Clinical personnel
      involved in patient care must embody the quality assurance process in daily work
      to ensure program sustainability. In conformance with the German Federal
      Government's concept for modern departmental research, the international standard
      ISO 9001, one of the relevant standards of the International Organization for
      Standardization (ISO), is applied in quality assurance in military medical
      research. By its holistic approach, this internationally accepted standard
      provides an excellent basis for establishing a modern quality management system
      in line with international standards. Furthermore, this standard can serve as a
      sound basis for the further development of an already established quality
      management system when additional standards shall apply, as for instance in
      reference laboratories or medical laboratories. Besides quality assurance, a
      military medical facility must manage additional risk events in the context of
      early recognition/detection of health risks of military personnel on deployment
      in order to be able to take appropriate preventive and protective measures; for
      instance, with medical radiation accident management. The international standard
      ISO 31000:2009 can serve as a guideline for establishing risk management. Clear
      organizational structures and defined work processes are required when individual
      laboratory units seek accreditation according to specific laboratory standards.
      Furthermore, international efforts to develop health laboratory standards must be
      reinforced that support sustainable quality assurance, as in the exchange and
      comparison of test results within the scope of external quality assurance, but
      also in the exchange of special diagnosis data among international research
      networks. In summary, the acknowledged standard for a quality management system
      to ensure quality assurance is the very generic standard ISO 9001.Health Phys.
      103(2):221-225; 2012.

PMID- 22951486
TI  - Histone H3 lysine 4 monomethylation (H3K4me1) and H3 lysine 9 monomethylation
      (H3K9me1): distribution and their association in regulating gene expression under
      hyperglycaemic/hyperinsulinemic conditions in 3T3 cells.
AB  - Hyperglycemia/hyperinsulinemia are leading cause for the induction type 2
      diabetes and the role of post-translational histone modifications in
      dysregulating the expression of genes has emerged as potential important
      contributor in the progression of disease. The paradoxical nature of histone H3
      Lysine 4 and Lysine 9 mono-methylation (H3K4me1 and H3K9me1) in both gene
      activation and repression motivated us to elucidate the functional relationship
      of these histone modifications in regulating expression of genes under
      hyperglycaemic/hyperinsulinemic condition. Chromatin immunoprecipitation
      microarray analysis (ChIP-chip) was performed with H3 acetylation, H3K4me1 and
      H3K9me1 antibody. CLUSTER analysis of ChIP-chip (Chromatin immunoprecipitation
      microarray analysis) data showed that mRNA expression and H3 acetylation/H3K4me1
      levels on genes were inversely correlated with H3K9me1 levels on the transcribed
      regions, after 30 min of insulin stimulation under hyperglycaemic condition.
      Interestingly, we provide first evidence regarding regulation of histone
      de/acetylases and de/methylases; Myst4, Jmjd2b, Aof1 and Set by H3Ac, H3K4me1 and
      H3K9me1 under hyperinsulinemic/hyperglycaemic condition. ChIP-qPCR analysis shows
      association of increased H3Ac/H3K4me1 and decreased levels of H3K9me1 in up
      regulation of Myst4, Jmjd2, Set and Aof1 genes. We further analyse promoter
      occupancy of histone modifications by ChIP walking and observed increased
      occupancy of H3Ac/H3K4me1 on promoter region (-1000 to -1) of active genes and
      H3K9me1 on inactive genes under hyperglycemic/hyperinsulinemic condition. To best
      of our knowledge this is the first report that shows regulation of chromatin
      remodelling genes by alteration in the occupancy of histone H3Ac/H3K4/K9me on
      both promoter and transcribed regions.

PMID- 22951487
TI  - Development and comparison of a rapid isothermal nucleic acid amplification test
      for typing of herpes simplex virus types 1 and 2 on a portable fluorescence
      detector.
AB  - We have developed a rapid and simple molecular test, the IsoGlow HSV Typing
      assay, for the detection and typing of herpes simplex virus (type 1 and 2) from
      genital or oral lesions. Clinical samples suspended in viral transport mediums
      are simply diluted and then added to a helicase-dependent amplification master
      mix. The amplification and detection were performed on a portable fluorescence
      detector called the FireFly instrument. Detection of amplification products is
      based on end-point analysis using cycling probe technology. An internal control
      nucleic acid was included in the amplification master mix to monitor the presence
      of amplification inhibitors in the samples. Because the device has only two
      fluorescence detection channels, two strategies were developed and compared to
      detect the internal control template: internal control detected by melting curve
      analysis using a dual-labeled probe, versus internal control detection using end
      point fluorescence release by a CPT probe at a lower temperature. Both have a
      total turnaround time of about 1 hour. Clinical performance relative to herpes
      viral culture was evaluated using 176 clinical specimens. Both formats of the
      IsoGlow HSV typing assay had sensitivities comparable to that of the Food and
      Drug Administration-cleared IsoAmp HSV (BioHelix Corp., Beverly MA) test and
      specificity for the two types of HSV comparable to that of ELVIS HSV (Diagnostic
      Hybrids, Athens, OH).

PMID- 22951488
TI  - [Prospective economic evaluation of image-guided radiation therapy for prostate
      cancer in the framework of the national programme for innovative and costly
      therapies assessment].
AB  - PURPOSE: The main objective of the economical study was to prospectively and
      randomly assess the additional costs of daily versus weekly patient positioning
      quality control in image-guided radiotherapy (IGRT), taking into account the
      modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A
      secondary objective was to prospectively assess the additional costs of 3D versus
      2D imaging with portal imaging for patient positioning controls. PATIENTS AND
      METHODS: Economics data are issued from a multicenter randomized medico-economics
      trial comparing the two frequencies of patient positioning control during
      prostate IGRT. A prospective cohort with patient positioning control with PI
      (control group) was constituted for the cost comparison between 3D (IGRT) versus
      2D imaging. The economical evaluation was focused to the radiotherapy direct
      costs, adopting the hospital's point of view and using a microcosting method
      applied to the parameters that may lead to cost differences between evaluated
      strategies. RESULTS: The economical analysis included a total of 241 patients
      enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128
      with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to
      weekly controls, the average additional cost per patient of daily controls was
      ?847 (CBCT) and ?179 (markers). Compared to PI, the average additional cost per
      patient was ?1392 (CBCT) and ?997 (fiducial markers) for daily controls; ?545
      (CBCT) and ?818 (markers) in case of weekly controls. CONCLUSION: A daily
      frequency for image control in IGRT and 3D images patient positioning control
      (IGRT) for prostate cancer lead to significant additional cost compared to weekly
      control and 2D imaging (PI). Long-term clinical assessment will permit to assess
      the medico-economical ratio of these innovative radiotherapy modalities.

PMID- 22951489
TI  - nBu4NI-catalyzed direct synthesis of alpha-ketoamides from aryl methyl ketones
      with dialkylformamides in water using TBHP as oxidant.
AB  - A novel and easy practical direct synthesis of alpha-ketoamides has been
      developed without metals in water. This procedure was catalyzed by nBu(4)NI using
      TBHP as oxidant from simple substrates, aryl methyl ketones and
      dialkylformamides.

PMID- 22951490
TI  - Pre-existing mutations in the rilpivirine Phase III trials ECHO and THRIVE:
      prevalence and impact on virological response.
AB  - BACKGROUND: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor
      (NNRTI), was approved for HIV-1 infected, antiretroviral treatment-naive adults
      based on data from two Phase III trials. In the screening population, the
      prevalence of 49 NNRTI resistance-associated mutations (RAMs) and the impact of
      allowed NNRTI RAMs on virological response to an RPV- or efavirenz (EFV)
      containing regimen were analysed. METHODS: ECHO and THRIVE were global, Phase
      III, doubleblind, double-dummy, randomized trials in antiretroviral treatment
      naive, HIV-1-infected adults to determine whether RPV 25 mg once daily had non
      inferior efficacy versus EFV 600 mg once daily, both given with
      tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine
      or abacavir/lamivudine (THRIVE). The prevalence of 49 NNRTI RAMs, including the
      predefined list of 39 NNRTI RAMs used to exclude patients with potential
      resistance to RPV or EFV, was investigated at screening by population sequencing
      (including mixtures) using the virco((r))TYPE HIV-1 genotyping assay. RESULTS: Of
      the 1,796 screened patients in whom genotypic resistance results were available,
      372 (21%) had NNRTI RAMs. Of 527 screening failures, 148 (28%) were due to the
      presence of NNRTI RAMs. The presence of allowed NNRTI RAMs was associated with
      comparable response rates to the overall population (RPV 84.3% versus EFV 82.3%,
      intent-to-treat time-to-loss-of-virological-response): V90I (82.4% and 100% for
      RPV and EFV, respectively), V106I (85.7% and 93.3%), V179I (87.7% and 94.0%) and
      V189I (100.0% and 88.9%). CONCLUSIONS: Analysis of the ECHO and THRIVE screened
      population suggests that transmitted NNRTI resistance is prevalent in treatment
      naive patients but prevalence of the 15 RPV RAMs remains low. The four allowed
      NNRTI RAMs present at baseline did not affect RPV response at week 48.

PMID- 22951491
TI  - Hip posterolateral musculature strengthening in sedentary women with
      patellofemoral pain syndrome: a randomized controlled clinical trial with 1-year
      follow-up.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To determine if adding hip
      strengthening exercises to a conventional knee exercise program produces better
      long-term outcomes than conventional knee exercises alone in women with
      patellofemoral pain syndrome (PFPS). BACKGROUND: Recent studies have shown that a
      hip-strengthening program reduces pain and improves function in individuals with
      PFPS. However, there are no clinical trials evaluating long-term outcomes of this
      type of program compared to conventional knee-strengthening and -stretching
      exercises. METHODS: Fifty-four sedentary women between 20 and 40 years of age,
      with a diagnosis of unilateral PFPS, were randomly assigned knee exercise (KE) or
      knee and hip exercise (KHE). The women in the KE group (n = 26; mean age, 23
      years) performed a 4-week conventional knee-stretching and -strengthening
      program. The women in the KHE group (n = 28; mean age, 22 years) performed the
      same exercises as those in the KE group, as well as strengthening exercises for
      the hip abductors, lateral rotators, and extensors. An 11-point numeric pain
      rating scale, the Lower Extremity Functional Scale, the Anterior Knee Pain Scale,
      and a single-hop test were used as outcome measures at baseline (pretreatment)
      and 3, 6, and 12 months posttreatment. RESULTS: At baseline, demographic, pain,
      and functional assessment data were similar between groups. Those in the KHE
      group had a higher level of function and less pain at 3, 6, and 12 months
      compared to baseline (P<.05). In contrast, the KE group had reduced pain only at
      the 3- and 6-month follow-ups (P<.05), without any changes in Lower Extremity
      Functional Scale, Anterior Knee Pain Scale, or hop testing (P>.05) through the
      course of the study. Compared to the KE group, the KHE group had less pain and
      better function at 3, 6, and 12 months posttreatment (P<.05). For the Lower
      Extremity Functional Scale, the between-group difference in change scores from
      baseline at 3, 6, and 12 months posttreatment favored the KHE group by 22.0,
      22.0, and 20.8 points, respectively. CONCLUSION: Knee-stretching and 
      strengthening exercises supplemented by hip posterolateral musculature
      strengthening exercises were more effective than knee exercises alone in
      improving long-term function and reducing pain in sedentary women with PFPS.

PMID- 22951492
TI  - An efficient synthesis of 2-bromo(chloro)-3-selenyl(sulfenyl)indoles via tandem
      reactions of 2-(gem-dibromo(chloro)vinyl)anilines with diselenides(disulfides).
AB  - A novel and efficient synthesis of 2-bromo(chloro)-3-selenyl(sulfenyl)indoles
      through tandem reactions of 2-(gem-dibromo(chloro)vinyl)-N-methylsulfonylanilines
      with diselenides and disulfides in the presence of t-BuOLi and I(2) (10 mol%) in
      DMSO was developed. The reactions generated the desired products in good yields
      with high regio-selectivity under transition-metal-free conditions in one-pot.

PMID- 22951493
TI  - Cryptosporidiosis surveillance--United States, 2009-2010.
AB  - PROBLEM/CONDITION: Cryptosporidiosis is a nationally notifiable gastrointestinal
      illness caused by extremely chlorine-tolerant protozoa of the genus
      Cryptosporidium. REPORTING PERIOD: 2009-2010. SYSTEM DESCRIPTION: Fifty state and
      two metropolitan public health agencies voluntarily report cases of
      cryptosporidiosis through CDC's National Notifiable Diseases Surveillance System.
      RESULTS: For 2009, 7,656 confirmed and probable cases of cryptosporidiosis (2.5
      per 100,000 population) were reported; for 2010, 8,951 confirmed and probable
      cases (2.9 per 100,000 population) were reported. All jurisdictions reported
      cryptosporidiosis cases for 2009-2010, and the number of jurisdictions reporting
      >3.5 cases per 100,000 population was 18 for 2009 and 20 for 2010. Cases were
      most frequently reported in children aged 1-9 years, followed by adults aged 25
      29 years. This is the first reporting period in which more cases of
      cryptosporidiosis were reported in females than in males. Peak onset of illness
      occurred during early summer through early fall; the sympton onset of cases in
      children aged 5-9 years peaked earlier than that of cases reported in adults aged
      25-34 years. INTERPRETATION: Transmission of Cryptosporidium occurs throughout
      the United States. Rate data from reporting jurisdictions should be compared with
      caution because individual jurisdictions have varying capacities to detect,
      investigate, and report cases. The symptom onset and age-specific peaks coincide
      with the summer recreational water season and might reflect increased use of
      communal swimming venues (e.g., swimming pools and interactive fountains) by
      young children who then transmit the parasite to other users and their
      caregivers. PUBLIC HEALTH ACTION: Local, state, and federal public health
      agencies can use cryptosporidiosis surveillance data to characterize the
      epidemiology of cryptosporidiosis in the United States, establish public health
      priorities (e.g., research) to improve cryptosporidiosis prevention and control,
      and design and evaluate efforts (e.g., health communication and policy) to
      prevent and control the transmission of Cryptosporidium.

PMID- 22951494
TI  - Giardiasis surveillance--United States, 2009-2010.
AB  - PROBLEM/CONDITION: Giardiasis is a nationally notifiable gastrointestinal illness
      caused by the protozoan parasite Giardia intestinalis. REPORTING PERIOD: 2009
      2010. SYSTEM DESCRIPTION: State, commonwealth, territorial, and two metropolitan
      health departments voluntarily report cases of giardiasis through CDC's National
      Notifiable Diseases Surveillance System. RESULTS: During 2009-2010, the total
      number of reported cases of giardiasis increased slightly from 19,403 for 2009 to
      19,888 for 2010. During this period, 50 jurisdictions reported giardiasis cases.
      A larger number of case reports were received for children aged 1-9 years than
      with other age groups. The number of cases peaked annually during early summer
      through early fall. INTERPRETATION: Transmission of giardiasis occurs throughout
      the United States, with more frequent diagnosis or reporting occurring in
      northern states. However, state incidence figures should be compared with caution
      because surveillance capacity differs between states. Giardiasis is reported more
      frequently in young children, which might reflect increased contact with
      contaminated water or ill persons. PUBLIC HEALTH ACTION: Local and state health
      departments can use giardiasis surveillance data to better understand the
      epidemiologic characteristics and the disease burden of giardiasis in the United
      States, design efforts to prevent the spread of disease, and establish research
      priorities.

PMID- 22951495
TI  - Pyrolysis and dehalogenation of plastics from waste electrical and electronic
      equipment (WEEE): a review.
AB  - Plastics from waste electrical and electronic equipment (WEEE) have been an
      important environmental problem because these plastics commonly contain toxic
      halogenated flame retardants which may cause serious environmental pollution,
      especially the formation of carcinogenic substances polybrominated dibenzo
      dioxins/furans (PBDD/Fs), during treat process of these plastics. Pyrolysis has
      been proposed as a viable processing route for recycling the organic compounds in
      WEEE plastics into fuels and chemical feedstock. However, dehalogenation
      procedures are also necessary during treat process, because the oils collected in
      single pyrolysis process may contain numerous halogenated organic compounds,
      which would detrimentally impact the reuse of these pyrolysis oils. Currently,
      dehalogenation has become a significant topic in recycling of WEEE plastics by
      pyrolysis. In order to fulfill the better resource utilization of the WEEE
      plastics, the compositions, characteristics and dehalogenation methods during the
      pyrolysis recycling process of WEEE plastics were reviewed in this paper.
      Dehalogenation and the decomposition or pyrolysis of WEEE plastics can be carried
      out simultaneously or successively. It could be 'dehalogenating prior to
      pyrolysing plastics', 'performing dehalogenation and pyrolysis at the same time'
      or 'pyrolysing plastics first then upgrading pyrolysis oils'. The first strategy
      essentially is the two-stage pyrolysis with the release of halogen hydrides at
      low pyrolysis temperature region which is separate from the decomposition of
      polymer matrixes, thus obtaining halogenated free oil products. The second
      strategy is the most common method. Zeolite or other type of catalyst can be used
      in the pyrolysis process for removing organohalogens. The third strategy separate
      pyrolysis and dehalogenation of WEEE plastics, which can, to some degree, avoid
      the problem of oil value decline due to the use of catalyst, but obviously, this
      strategy may increase the cost of whole recycling process.

PMID- 22951496
TI  - Recent progress on preparation and properties of nanocomposites from recycled
      polymers: a review.
AB  - Currently, the growing consumption of polymer products creates the large
      quantities of waste materials resulting in public concern in the environment and
      people life. Nanotechnology is assumed the important technology in the current
      century. Recently, many researchers have tried to develop this new science for
      polymer recycling. In this article, the application of different nanofillers in
      the recycled polymers such as PET, PP, HDPE, PVC, etc. and the attributed
      composites and blends is studied. The morphological, mechanical, rheological and
      thermal properties of prepared nanocomposites as well as the future challenges
      are extensively discussed. The present article determines the current status of
      nanotechnology in the polymer recycling which guide the future studies in this
      attractive field.

PMID- 22951498
TI  - Root cause analysis.

PMID- 22951497
TI  - Courage and character, leaders and legends: an interview with Rear Admiral
      Kenneth P. Moritsugu, MD, MPH.

PMID- 22951499
TI  - Practice pattern and professional issues of nurse practitioners in mechanical
      circulatory support programs in the United States: a survey report.
AB  - CONTEXT: Few data-based reports about the role and work environment of advanced
      practice nurses, specifically nurse practitioners in mechanical circulatory
      support programs, have been published. OBJECTIVE: To describe the practice
      pattern and professional issues confronted by nurse practitioners in the rapidly
      evolving and expanding mechanical circulatory support programs in the United
      States. DESIGN: A descriptive research design was employed using the data from
      the 2010 mechanical circulatory support nurses survey. Quantitative and
      qualitative data that pertained to the demographic and practice profiles as well
      as barriers and overall issues faced by the nurse practitioners in their clinical
      practice were analyzed. PARTICIPANTS: Nonrandom sample of 48 nurse practitioners
      from 95 mechanical circulatory support programs nationwide. RESULTS: The practice
      pattern of nurse practitioners in mechanical circulatory support programs is
      similar to the practice pattern reported for nurse practitioners in acute and
      critical care settings. However, only 44% and 10% of nurse practitioners in
      mechanical circulatory support programs are authorized to admit and transfer
      patients into and out of the hospital, respectively. High workload, lack of
      institutional support, knowledge deficit, role ambiguity, lack of professional
      recognition, and burnout were the common issues faced by the participants in
      their clinical practice. CONCLUSION: The results provide preliminary evidence on
      the practice pattern, restrictions, and work environment issues that may threaten
      the viability of an mechanical circulatory support program in which nurse
      practitioners play a crucial role. Implications for clinical practice, research,
      and policy development are discussed.

PMID- 22951500
TI  - Bone loss after heart transplant: effect of alendronate, etidronate, calcitonin,
      and calcium plus vitamin D3.
AB  - OBJECTIVE: To compare the effects of calcitonin, etidronate, and alendronate in
      preventing bone loss during the first 2 years after heart transplant. METHODS: A
      total of 222 heart transplant recipients (mean [SD] age, 52.4 [10] years, 85%
      male) were evaluated. Patients with normal bone mineral density (reference group,
      n = 102) received 1000 mg/d calcium plus 800 IU/d vitamin D3. The rest were
      assigned to 200 IU/d of calcitonin (n=42), 400 mg/d etidronate orally for 14 days
      quarterly (n = 33), or 10 mg/d alendronate (n = 45). All patients received
      calcium and vitamin D. Bone mineral density was assessed by dual-energy x-ray
      absorptiometry in the lumbar spine, the entire femur, and the femoral neck at
      baseline and 6, 12, and 24 months after transplant. RESULTS: At 2 years after
      transplant, bone mineral density in the lumbar spine had decreased in the
      reference group (-3.07%), calcitonin group (-0.93%), and etidronate group (
      1.87%) but not in the alendronate group (+4.9%; P <.001). After 2 years, bone
      mineral density in the entire femur decreased in all groups (-3.2% in the
      reference group, -3.6% in the calcitonin group, -4.6% in the etidronate group,
      and -0.5% in the alendronate group) but bone loss was significantly lower in the
      alendronate group (P <.001). Bone mineral density in the femoral neck also
      decreased in all groups. The incidence of vertebral fractures did not differ
      among groups. Adverse events were similar between groups. CONCLUSIONS:
      Alendronate therapy in heart transplant recipients was associated with a
      significant increase in bone mineral density in the lumbar spine and less bone
      loss at the hip.

PMID- 22951501
TI  - Older adolescents' experiences living with a parent who is a transplant patient.
AB  - This descriptive qualitative study using telephone interviews and surveys
      explored how parental transplant status affected older adolescents. A sample of 8
      adolescents (62% female) between 15 and 20 years old participated. Findings
      revealed "a normal life." Other themes were feeling the impact, worrying, coping,
      and keeping healthy. Parental transplant status had positive and negative
      effects. No evidence was found of signs or symptoms of depression. Transplant
      candidates' children worried about "something going wrong"; recipients' children
      worried about organ rejection. Most stated that parental transplant status did
      not influence career plans, jobs, or friends. Strategies and recommendations for
      practice and future research are discussed.

PMID- 22951502
TI  - Essential components of transition to adult transplant services: the transplant
      coordinators' perspective.
AB  - CONTEXT: Medical and surgical advancements have resulted in improved long-term
      survival of pediatric liver transplant recipients. As pediatric patients approach
      school age and adolescence, transplant centers are challenged to facilitate the
      process of transitioning from pediatric to adult centers. OBJECTIVE: To describe
      pediatric and adult liver transplant coordinators' perspective regarding practice
      for transitioning patients to adult-oriented transplant centers. DESIGN:
      Descriptive SETTING: Pediatric and adult liver transplant coordinators associated
      with Studies of Pediatric Liver Transplantation. PARTICIPANTS: A total of 35
      pediatric liver transplant coordinators and 24 adult liver transplant
      coordinators completed the survey. METHOD: Investigator-developed survey to
      identify current practice for transition process and actual transfer of a patient
      from pediatric to adult care. RESULTS: Transplant coordinators play an integral
      role in the transition process, and study results highlight what experienced
      coordinators believe are important considerations for a successful transition
      process. Results also highlight the importance of communication and partnership
      between the pediatric and adult programs.

PMID- 22951503
TI  - Body image and eating attitudes and behaviors among adolescent heart and lung
      transplant recipients: a brief report.
AB  - BACKGROUND: Adolescents with chronic illnesses are at increased risk for body
      image and eating disorders; however, this has not been investigated in solid
      organ transplant recipients. Adolescent transplant recipients are a vulnerable
      cohort because of the sustained follow-up and immune-suppressing therapies, which
      often include steroids and may lead to weight gain and cosmetic changes.
      Consequences of body dissatisfaction such as disordered behaviors have not been
      well studied in transplant recipients. PURPOSE: To examine body image, eating
      attitudes, and behaviors among 28 adolescent thoracic transplant recipients.
      METHODS: Adolescent (11-18 years old) heart and lung transplant recipients a
      minimum of 3 months after transplant provided informed written consent and
      completed a standardized questionnaire package about eating attitudes and
      behaviors; body image and drive for thinness; actual, perceived, and desired
      weight; and medical and anthropometric information (eg, body mass index) during
      regular transplant clinics. RESULTS: Of 25 heart and 3 lung transplant recipients
      (54% female; median age, 14.5 years; median, 1.6 years after transplant), 37%
      perceived their current weight as too high or low. Moreover, 81% were
      dissatisfied with their current weight (38% wanted to lose and 44% wanted to gain
      weight), yet few engaged in disordered behaviors. CONCLUSIONS: Despite high
      levels of self-reported body dissatisfaction, low rates of disordered behaviors
      were observed. Weight dissatisfaction was high (81%) but bidirectional (to lose
      or to gain weight). Future assessment of disordered eating behaviors should
      include insidious activities such as medication nonadherence, in addition to
      traditional weight-control behaviors such as binge eating, strict dieting, or
      assiduous exercise. Further research will delineate the impact of body
      dissatisfaction and eating behaviors and outcomes on long-term transplant
      survivors, older adolescent cohorts, and other recipients of solid organ
      transplants.

PMID- 22951504
TI  - Implementing a standardized, evidence-based education program using the patient's
      electronic file for lung transplant recipients.
AB  - CONTEXT: Patient education is crucial to guarantee that transplant recipients are
      capable of adequate self-management. Until recently, our education program to
      prepare lung transplant patients for discharge lacked a systematic approach,
      meaning that it was unclear whether all key information had been provided and
      whether the patient understood the information. A lack of coordination among the
      multidisciplinary team members also was apparent. OBJECTIVES: (1) To map out a
      structured education program, outlining the content, process, and evaluation of
      education for patients before discharge after lung transplant; (2) to integrate
      this program into the patient's electronic file and pilot test this new form of
      education tracking. METHODS: We used the conceptual framework of Lorig and
      colleagues, as well as the educational leaflets of the International Transplant
      Nurses Society, to generate the content of our education program. The
      interdisciplinary lung transplant team decided when and by whom each educational
      component should be provided, as well as the evaluation criteria. Next,
      information technology engineers integrated this educational program into the
      patient's electronic file. Nurses subsequently tested the program, and their
      feedback was integrated in the next version of the program. RESULTS: Health care
      providers experienced a higher level of uniformity and transparency. After using
      the education program, most patients indicated that they felt confident to go
      home. CONCLUSION: Our electronic educational platform is promising, yet further
      testing is necessary to evaluate whether patients indeed have sufficient
      knowledge and show adequate self-management skills in the long term after
      transplant.

PMID- 22951505
TI  - The lived experience of peripheral neuropathy after solid organ transplant.
AB  - BACKGROUND: The immunosuppressants required after transplant cause peripheral
      neuropathy with an incidence of 10% to 60%. Peripheral neuropathy adversely
      affects health-related quality of life in other populations. OBJECTIVE: To
      describe the lived experience of peripheral neuropathy after solid organ
      transplant. DESIGN: A qualitative phenomenological study with semistructured
      interviews. A purposive sample of 7 solid organ transplant recipients with
      peripheral neuropathy was recruited from 2 transplant clinics at a large Midwest
      tertiary care center. Interviews were audio taped and transcribed verbatim. Data
      were analyzed line-by-line and coded by using HyperResearch 2.0. RESULTS:
      Although participants' experiences were similar to those reported by others with
      peripheral neuropathy, there were also unique differences. Unique to this
      population was unexpected onset, rapid escalation of symptoms, lack of provider
      monitoring, and poor provider response to reported symptoms. Their experience
      demonstrated that peripheral neuropathy diminished health-related quality of
      life. Four themes emerged from the data: (1) nothing is supposed to happen after
      transplant; (2) neuropathy causes me more problems than my heart; (3) maybe there
      is something that could help; and (4) I've learned to live with certain
      limitations. CONCLUSION: Development of or worsening of peripheral neuropathy
      after solid organ transplant may decrease health-related quality of life. Follow
      up care should include vigilant monitoring for signs of peripheral neuropathy.
      Providers need to provide early treatment, education, support, empathy, and
      understanding.

PMID- 22951507
TI  - Quality of Internet education about living kidney donation for Hispanics.
AB  - CONTEXT: Hispanics need disproportionately more kidney transplants, yet receive
      disproportionately fewer kidney transplants and living donor kidney transplants
      than non-Hispanic whites. Lack of knowledge and cultural beliefs about living
      kidney donation contribute to these disparities. The Internet is an optimal venue
      to educate underserved, low-literacy populations. DESIGN: Websites were evaluated
      for information on living kidney donation targeted to Hispanics. Hispanic
      websites addressing living kidney donation were identified through the Google
      search engine, using the search terms Hispanic, Latino, Spanish, and living
      kidney donor/donation. Websites were evaluated for accessibility of information,
      readability, and content required by 9 Centers for Medicare and Medicaid Services
      regulations representing 12 topics, and cultural competency. RESULTS: Twenty
      resources met inclusion criteria. Websites contained 2.3 pages on living kidney
      donation and required 2.4 links to access all information on living kidney
      donation. Websites were written at the 9th grade reading level. Sites described
      alternative treatments for recipients (n = 14), the evaluation process (n = 7),
      and the surgical procedure (n=6). Few addressed psychosocial risks (n=2). Some
      contained culturally sensitive colors and pictures (n = 8), but few addressed
      Hispanic cultural beliefs (n = 4). CONCLUSIONS: A comprehensive website on living
      kidney donation that provides more robust content and is targeted to Hispanics is
      needed to increase Hispanics' understanding of treatment options.

PMID- 22951508
TI  - Predicting willingness to donate organs according to the demographic
      characteristics of the deceased's family.
AB  - BACKGROUND: Transplant professionals need to gain a better understanding of the
      factors that facilitate willingness to donate a family member's organs, in order
      to increase the rate of organ donation. OBJECTIVE: To conduct an integrated
      analysis of demographic data relating to key family members, so as to help
      transplant professionals predict the likelihood that family members would be
      willing to donate organs. METHOD: Demographic variables were collected on 753
      brain-dead patients and 995 first-degree relatives in 20 Israeli hospitals from
      2004 to 2009. The data were recorded by transplant coordinators who used a
      uniform format to document meetings with next of kin. The data were analyzed by
      using the Chaid Statistical Test from the SPSS statistical package. RESULTS: In
      this total study population, the most significant factor affecting the decision
      to donate was religion. With increasing religiousness, the likelihood of consent
      decreased. A large disparity was apparent among Moslems, Christians, and Jews.
      Within the religious groups, education (Jews), familial proximity to the deceased
      (Christians and Moslems), and the quality of relationships with the medical staff
      (Moslems) were the main predictors of consent. SUMMARY: Most countries have
      Christian, Moslem, and Jewish residents, so the conclusions of this study and its
      implications for practice should be relevant for transplant coordinators
      anywhere. The recommendations, which stem from the results of this study, relate
      to activities of transplant coordinators before and during their interaction with
      families, before the request for organ donation.

PMID- 22951506
TI  - Prevention of poor psychosocial outcomes in living organ donors: from description
      to theory-driven intervention development and initial feasibility testing.
AB  - CONTEXT: Although some living donors experience psychological, somatic, and
      interpersonal difficulties after donation, interventions to prevent such outcomes
      have not been developed or evaluated. OBJECTIVE: To (1) summarize empirical
      evidence on psychosocial outcomes after donation, (2) describe a theoretical
      framework to guide development of an intervention to prevent poor outcomes, and
      (3) describe development and initial evaluation of feasibility and acceptability
      of the intervention. METHODS: Based on a narrative literature review suggesting
      that individuals ambivalent about donation are at risk for poor psychosocial
      outcomes after donation, the intervention targeted this risk factor. Intervention
      structure and content drew on motivational interviewing principles in order to
      assist prospective donors to resolve ambivalence. Data were collected on donors'
      characteristics at our institution to determine whether they constituted a
      representative population in which to evaluate the intervention. Study
      participants were then recruited to assess the feasibility and acceptability of
      the intervention. They were required to have scores greater than 0 on the Simmons
      Ambivalence Scale (indicating at least some ambivalence about donation). RESULTS:
      Our population was similar to the national living donor population on most
      demographic and donation-related characteristics. Eight individuals who had been
      approved to donate either a kidney or liver segment were enrolled for pilot
      testing of the intervention. All successfully completed the 2-session telephone
      based intervention before scheduled donation surgery. Participants' ratings of
      acceptability and satisfaction were high. Open-ended comments indicated that the
      intervention addressed participants' thoughts and concerns about the decision to
      donate. CONCLUSIONS: The intervention is feasible, acceptable, and appears
      relevant to donor concerns. A clinical trial to evaluate the efficacy of the
      intervention is warranted.

PMID- 22951509
TI  - The organ donation conundrum.
AB  - A discrepancy exists between the demand for and the availability of solid organs
      for transplant. Barriers to organ donation can be encountered at 2 key points:
      (1) when trying to increase the number of people willing to become organ donors
      and registering their intent and (2) at the time of organ procurement. Several
      predictors of individual willingness to register as an organ donor are discussed,
      along with issues surrounding families' refusal of consent or failures in the
      hospital system to identify potential donors. Several countries have adopted
      presumed-consent policies and have seen a subsequent increase in donation rates.
      Research is needed to explore the effectiveness of approaches to overcome the
      barriers to individual registration and family consent, particularly in countries
      where presumed consent has not been and is not likely to be adopted.

PMID- 22951510
TI  - Personal attitudes and beliefs regarding organ and tissue donation: a cross
      sectional survey of Australian emergency department clinicians.
AB  - CONTEXT: Resources are currently targeted at increasing organ and tissue donation
      rates from emergency departments in Australia. Health care professionals' beliefs
      and personal attitudes regarding organ and tissue donation are known to influence
      professional attitudes and practice. OBJECTIVE: To assess emergency department
      clinicians' general beliefs and personal attitudes toward organ and tissue
      donation, how general beliefs influence personal attitudes, and which demographic
      characteristics are related. DESIGN: A cross-sectional online survey, based on
      available literature and the validated and widely used Hospital Attitude Survey
      (DonorAction). PARTICIPANTS: Data were collected from 811 Australian emergency
      department clinicians, invited to participate through the College of Emergency
      Nursing Australasia, and the Australasian College for Emergency Medicine.
      RESULTS: Most clinicians were very supportive of organ and tissue donation
      (96.2%), believed that organ and tissue donation can save lives (98.5%), and that
      organs and tissues will be allocated fairly (82.6%); however, 30.1% did not agree
      that organ and tissue donation can help the next of kin cope with grief. Holding
      positive general beliefs increased positive personal attitudes toward organ and
      tissue donation (P < .001). Most reported willingness to donate their own organs
      and tissues after death (90%) and give family consent for their children (79.6%)
      or adult family (86.6%) member to donate. Eighty-six percent had discussed their
      wishes with next of kin, but only 50.7% had registered on the Australian Organ
      Donor Register. Older clinicians, male clinicians, and clinicians of certain
      religious and cultural backgrounds were identified as having less positive
      general beliefs and personal attitudes. CONCLUSION: Although Australian emergency
      department clinicians are generally positive toward organ and tissue donation,
      some groups could potentially benefit from education to change their beliefs and
      attitudes about organ and tissue donation further.

PMID- 22951511
TI  - A sequential decision framework for increasing college students' support for
      organ donation and organ donor registration.
AB  - CONTEXT: Despite the fact that college students support social causes, this age
      group has underparticipated in organ donor registration. Little research
      attention has been given to understanding deeper, higher-order relationships
      between the antecedent attitudes toward and perceptions of organ donation and
      registration behavior. OBJECTIVE: To test a process model useful for
      understanding the sequential ordering of information necessary for moving college
      students along a hierarchical decision-making continuum from awareness to support
      to organ donor registration. DESIGN AND SETTING: The University of Wisconsin
      organ procurement organization collaborated with the Collegiate American
      Marketing Association on a 2-year grant funded by the US Health Resources and
      Services Administration. A total of 981 association members responded to an
      online questionnaire. MEASURES: The 5 antecedent measures were awareness of organ
      donation, need acknowledgment, benefits of organ donation, social support, and
      concerns about organ donation. The 2 consequence variables were support for organ
      donation and organ donation registration. RESULTS: Structural equation modeling
      indicated that 5 of 10 direct antecedent pathways led significantly into organ
      donation support and registration. The impact of the nonsignificant variables was
      captured via indirect effects through other decision variables. Model fit
      statistics were good: the goodness of fit index was .998, the adjusted goodness
      of fit index was .992, and the root mean square error of approximation was .001.
      IMPLICATIONS: This sequential decision-making model provides insight into the
      need to enhance the acceptance of organ donation and organ donor registration
      through a series of communications to move people from awareness to behavior.

PMID- 22951512
TI  - An analytical tool that quantifies cellular morphology changes from three
      dimensional fluorescence images.
AB  - The most common software analysis tools available for measuring fluorescence
      images are for two-dimensional (2D) data that rely on manual settings for
      inclusion and exclusion of data points, and computer-aided pattern recognition to
      support the interpretation and findings of the analysis. It has become
      increasingly important to be able to measure fluorescence images constructed from
      three-dimensional (3D) datasets in order to be able to capture the complexity of
      cellular dynamics and understand the basis of cellular plasticity within
      biological systems. Sophisticated microscopy instruments have permitted the
      visualization of 3D fluorescence images through the acquisition of multispectral
      fluorescence images and powerful analytical software that reconstructs the images
      from confocal stacks that then provide a 3D representation of the collected 2D
      images. Advanced design-based stereology methods have progressed from the
      approximation and assumptions of the original model-based stereology even in
      complex tissue sections. Despite these scientific advances in microscopy, a need
      remains for an automated analytic method that fully exploits the intrinsic 3D
      data to allow for the analysis and quantification of the complex changes in cell
      morphology, protein localization and receptor trafficking. Current techniques
      available to quantify fluorescence images include Meta-Morph (Molecular Devices,
      Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor
      Technology, Belfast, Northern Ireland) software provides the feature
      MeasurementPro, which allows the manual creation of measurement points that can
      be placed in a volume image or drawn on a series of 2D slices to create a 3D
      object. This method is useful for single-click point measurements to measure a
      line distance between two objects or to create a polygon that encloses a region
      of interest, but it is difficult to apply to complex cellular network structures.
      Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament
      like however, this module has been developed to measure defined structures such
      as neurons, which are comprised of dendrites, axons and spines (tree-like
      structure). This module has been ingeniously utilized to make morphological
      measurements to non-neuronal cells, however, the output data provide information
      of an extended cellular network by using a software that depends on a defined
      cell shape rather than being an amorphous-shaped cellular model. To overcome the
      issue of analyzing amorphous-shaped cells and making the software more suitable
      to a biological application, Imaris developed Imaris Cell. This was a scientific
      project with the Eidgenossische Technische Hochschule, which has been developed
      to calculate the relationship between cells and organelles. While the software
      enables the detection of biological constraints, by forcing one nucleus per cell
      and using cell membranes to segment cells, it cannot be utilized to analyze
      fluorescence data that are not continuous because ideally it builds cell surface
      without void spaces. To our knowledge, at present no user-modifiable automated
      approach that provides morphometric information from 3D fluorescence images has
      been developed that achieves cellular spatial information of an undefined shape
      (Figure 1). We have developed an analytical platform using the Imaris core
      software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools
      allow the 3D measurement of cells without a pre-defined shape and with
      inconsistent fluorescence network components. Furthermore, this method will allow
      researchers who have extended expertise in biological systems, but not
      familiarity to computer applications, to perform quantification of morphological
      changes in cell dynamics.

PMID- 22951515
TI  - TANF over time: the tale of three studies.
AB  - We compare the experiences of women from three studies who were in different
      stages of participation in the U.S. welfare program, Temporary Assistance for
      Needy Families (TANF). The setting for the studies was a large Midwest urban
      county, targeted chain referral sampling was used, and the combined sample of the
      three studies was 106 women. The instruments were a semistructured interview
      guide, the HANES General Well-Being Schedule and a demographic data form.
      Quantitative data are augmented with qualitative interview data. The findings
      suggest barriers to self-sustaining employment include health challenges, limited
      education, socio-economic marginalization, and the welfare policy itself. Nurses
      are well positioned to advocate for women in poverty and mitigate the health
      challenges they face. The findings add to the limited evidence base on which the
      TANF policy is based and can be used to modify the policy to increase the success
      of the women who participate in it.

PMID- 22951516
TI  - Electrocortical and ocular indices of attention to fearful and neutral faces
      presented under high and low working memory load.
AB  - Working memory load reduces the late positive potential (LPP), consistent with
      the notion that functional activation of the DLPFC attenuates neural indices of
      sustained attention. Visual attention also modulates the LPP. In the present
      study, we sought to determine whether working memory load might exert its
      influence on ERPs by reducing fixations to arousing picture regions. We
      simultaneously recorded eye-tracking and EEG while participants performed a
      working memory task interspersed with the presentation of task-irrelevant fearful
      and neutral faces. As expected, fearful compared to neutral faces elicited larger
      N170 and LPP amplitudes; in addition, working memory load reduced the N170 and
      the LPP. Participants made more fixations to arousing regions of neutral faces
      and faces presented under high working memory load. Therefore, working memory
      load did not induce avoidance of arousing picture regions and visual attention
      cannot explain load effects on the N170 and LPP.

PMID- 22951517
TI  - Lower stress system activity and higher peripheral inflammation in competitive
      ballroom dancers.
AB  - Although regular physical exercise is beneficial for health, competitive ballroom
      dancers anecdotally report increased disease susceptibility. This study aims to
      uncover possible biological mechanisms and pathways that may lead to higher
      disease susceptibility in a population of otherwise healthy young athletes.
      Experienced ballroom dancers and healthy controls provided blood and saliva
      samples in order to assess diurnal cortisol and alpha-amylase (sAA) output as
      well as inflammatory parameters interleukin (IL)-6 and C-reactive protein (CRP).
      We found diurnal cortisol and sAA output to be significantly lower in dancers.
      Additionally, higher levels in IL-6 but not in CRP were shown in dancers. Dancers
      described themselves as being more anxious and reported more physical health
      complaints. Competitive ballroom dancers show evidence for hypoactivity in stress
      systems and peripheral inflammation along with more self-reported physical
      complaints. Therefore, competitive ballroom dancing represents a chronic stressor
      that can lead to important functional consequences. It remains to be investigated
      whether these alterations are causally related to health.

PMID- 22951518
TI  - Immunogenicity of different stressed IgG monoclonal antibody formulations in
      immune tolerant transgenic mice.
AB  - The presence of protein aggregates in biopharmaceutical formulations is of great
      concern for safety and efficacy reasons. The aim of this study was to correlate
      the type and amount of IgG monoclonal antibody aggregates with their immunogenic
      potential. IgG degradation was obtained by freeze-thawing cycles, pH-shift
      cycles, heating, shaking and metal-catalyzed oxidation. The size, amount,
      morphology and type of intermolecular bonds of aggregates, as well as structural
      changes and epitope integrity were characterized. These formulations were
      injected in mice transgenic (TG) for human genes for Ig heavy and light chains
      and their non-transgenic (NTG) counterparts. Anti-drug antibody (ADA) titers were
      determined by bridging ELISA. Both unstressed IgG and freeze-thawed formulation
      did not induce measurable ADA levels. A mild antibody response was obtained in a
      fairly small percentage of mice, when injected with shaken, pH-shifted and heated
      formulations. The metal-catalyzed oxidized IgG formulation was the most
      immunogenic one, in both ADA titers and number of responders. The overall titers
      of NTG responders were significantly higher than the ones produced by TG mice,
      whereas there was no significant difference between the overall number of TG and
      NTG responders. This study reinforces the important role of protein aggregates on
      immunogenicity of therapeutic proteins and provides new insight into the
      immunogenic potential of different types of IgG aggregates. The results indicate
      that the quality of the IgG aggregates has more impact on the development of an
      immune response than their quantity or size.

PMID- 22951520
TI  - An association between uric acid levels and renal arteriolopathy in chronic
      kidney disease: a biopsy-based study.
AB  - Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is
      an association between UA and renal arteriolopathy in patients with chronic
      kidney disease (CKD) is unknown. Here, we examined the cross-sectional
      association of serum UA levels with renal arteriolar hyalinosis and wall
      thickening. Arteriolar parameters were assessed by semiquantitative grading (max:
      grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and
      81 women) who underwent renal biopsy. The mean serum UA level was 6.4 mg dl(-1).
      We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients
      (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2
      and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall
      thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age
      >=40 years, sex, hypertension status, diabetes mellitus status and estimated
      glomerular filtration rate <60 ml min(-1) per 1.73 m(2) showed that hyperuricemia
      (UA >=7 mg dl(-1)) was significantly associated with a higher risk of hyalinosis
      (adjusted odds ratio: 3.13; 95% confidence interval: 1.23-7.94; P=0.02) and
      higher-grade (equal to or higher than the mean value) wall thickening (adjusted
      odds ratio: 2.66; 95% confidence interval: 1.11-6.38; P=0.03). Hence, these
      results suggest that hyperuricemia may be related to renal arteriolar damage in
      patients with CKD.

PMID- 22951521
TI  - The effects of angiotensin receptor blockers vs. calcium channel blockers on the
      acute exercise-induced inflammatory and thrombotic response.
AB  - Arterial hypertension is an established risk factor for acute coronary syndromes,
      and physical exertion may trigger the onset of such an event. The mechanisms
      involved include the rupture of a small, inflamed, coronary plaque and the
      activation of thrombogenic factors. Blood pressure (BP)-lowering treatment has
      been associated with beneficial effects on subclinical inflammation and
      thrombosis at rest and during exercise. This prospective study sought to compare
      the effect of different antihypertensive drugs on the inflammatory and thrombotic
      response during exercise. A total of 60 never-treated hypertensive patients were
      randomized to an angiotensin receptor blocker (ARB)- or non-dihydropyridine
      calcium channel blocker (CCB)-based regimen. Patients with inflammatory or
      coronary artery disease were excluded. Six months after pharmaceutical BP
      normalization, the patients underwent a maximal treadmill exercise testing. High
      sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cells
      (WBC), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), total
      fibrinogen (TF) and von Willebrand factor (vWF) levels, as well as plasminogen
      activator inhibitor-1 (PAI-1) activity were measured in blood samples taken while
      the patients were at rest and during peak exercise. All of these biomarkers
      increased with exercise, except PAI-1, which decreased (P<0.05 for the difference
      between resting and peak exercise for all biomarkers). The ARB group had less
      marked (P<0.05) exercise-induced changes than the CCB group in hsCRP (5.8% vs.
      7.7%), SAA (4.2% vs. 7.2%), WBC (46.8% vs. 52.6%), TNF-alpha (16.3% vs. 24.3%),
      TF (9.5% vs. 16.9%) and PAI-1 (-9.5% vs. -12.3%) but a similar (P=NS) change in
      IL-6 (39.4% vs. 38.6%) and vWF (29.2% vs. 28.6%). In conclusion, ARBs are most
      likely more effective than CCBs at suppressing the exercise-induced acute phase
      response. Potential protection against exercise-related coronary events remains
      to be elucidated.

PMID- 22951522
TI  - Breastfeeding leads to lower blood pressure in 7-year-old Japanese children:
      Tohoku Study of Child Development.
AB  - This study investigated the association between breastfeeding and both self
      measured home blood pressure (HBP) and conventional blood pressure (CBP) in 7
      year-old Japanese children. We obtained data pertaining to breastfeeding and
      blood pressure for 377 mother-offspring pairs from the Tohoku Study of Child
      Development, which is a prospective birth cohort study. Information on
      breastfeeding and other factors were obtained from parental questionnaires during
      the follow-up period. Based on the duration of breastfeeding as a major source of
      nutrition, mother-offspring pairs were divided into short-term (mean, 5.1 months)
      and long-term (mean, 11.3 months) breastfeeding groups. At the age of 7 years
      (84.4+/-1.8 months), each child's blood pressure was measured. The HBP in the
      long-term breastfeeding (LBF) group (92.9 mm Hg systolic/55.1 mm Hg diastolic)
      was significantly lower (P=0.006/0.04) than in the short-term breastfeeding group
      (94.7/56.4 mm Hg); however, there were no significant differences in the CBP
      measurements between the short- and LBF groups. Using multiple regression
      analysis, the duration of breastfeeding (greater than 8 months) was more strongly
      associated with HBP (P=0.008/0.05) than with CBP (P=0.4/0.9). Furthermore, the
      adjusted R-squared values for HBP (0.25/0.12) tended to be higher than those for
      CBP (0.07/0.03). These findings were independent of the birth weight. In
      conclusion, breastfeeding has a protective effect against elevated blood pressure
      even in young children, and subtle, but important, differences were precisely
      detected by self-measurements performed at home.

PMID- 22951523
TI  - Do diabetes, metabolic syndrome or their association equally affect biventricular
      function? A tissue Doppler study.
AB  - Metabolic syndrome (MetS) and type 2 diabetes (T2DM) have been associated with an
      impairment of left (LV) and right ventricular (RV) function as well as an
      increased risk of heart failure (HF). However, it remains unclear whether these
      clinical entities or their associations promote a similar derangement of
      biventricular function. Overall, 345 patients without overt cardiovascular
      disease consecutively underwent routine blood chemistry including high
      sensitivity C reactive protein (hs-CRP) and echocardiographical examination with
      conventional and tissue Doppler imaging (TDI) of both ventricles. According to
      the ATP III criteria and fasting glucose levels, the study population was
      stratified into four groups: (1) healthy controls (n=120); (2) MetS without T2DM
      (n=84); (3) T2DM without MetS (n=49); and (4) MetS+T2DM (n=92). The Myocardial
      performance index (MPI) of the RV and LV was obtained with a multi-segmental
      approach using TDI. Patients with MetS and T2DM exhibited a similar impairment of
      biventricular function compared with healthy controls, whereas a further decline
      was observed in patients having both MetS and T2DM. In addition to MetS markers,
      hs-CRP exhibited the strongest association with the MPI of both ventricles.
      Regression analyses indicated that individual MetS markers were inferior to MetS
      in identifying subtle cardiac dysfunction. Independent associations of MetS and
      T2DM with biventricular dysfunction were comparable, and the coexistence of MetS
      and T2DM exhibited the highest risk for biventricular dysfunction. Our findings
      emphasize the importance of MetS as an equivalent of T2DM and support a synergic
      effect of these clinical conditions on cardiac organ damage requiring more
      aggressive therapeutic strategies to prevent HF.

PMID- 22951524
TI  - Lumican expression in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND/AIMS: The present study was aimed to investigate lumican expression in
      and correlation with severity of pancreatic ductal adenocarcinoma (PDA).
      METHODOLOGY: We assessed mRNA expression and protein localization (using
      immunohistochemistry) in PDA samples collected from 260 patients. Additionally,
      we compared lumican expression with expression of Ki-67, VEGF and mutated p53
      proteins, which are markers of cancer progression. RESULTS: Expression levels of
      lumican mRNA and protein in cancer tissue were significantly higher than those in
      tumor-adjacent tissue (t=5.69, p<0.05). The stromal expression of lumican in
      poorly differentiated cases was significantly higher at stage T4 than stage T2-3
      (chi2=21.06, p<0.05); similarly, the stromal expression of lumican was
      significantly higher in TNM stage III-IV than in stage I-Il (chi2=17.01, p<0.05).
      Additionally, expression of Ki67 was higher in poorly differentiated cases than
      in highly-moderately differentiated cases (chi2=13.06, p<0.05). Finally, in
      highly-moderately differentiated samples, stromal expression of lumican was
      negatively correlated with expression of Ki-67, VEGF and mutated P53 (p<0.05).
      CONCLUSIONS: Lumican expression is higher in pancreatic ductal adenocarcinoma
      than in tumor-adjacent tissue, and the correlation of lumican expression with TNM
      stage in poorly differentiated samples, in contrast with its negative correlation
      with expression of Ki-67, VEGF and mutated P53 mutation in highly-moderately
      differentiated samples.

PMID- 22951525
TI  - Clinical study of disseminated tumor cells in bone marrow of patients with
      gastric cancer.
AB  - BACKGROUND/AIMS: Tumor micrometastasis usually occurs at early stage. Therefore,
      we aimed to investigate the morphology of disseminated tumor cells (DTCs) and its
      clinical significance in bone marrow (BM) of patients with gastric cancer.
      METHODOLOGY: Forty patients with gastric cancer were enrolled and mononuclear
      cells were separated from BMs. After labeled by MACS microbeads conjugated with
      human epithelial antigen (HEA) antibodies, tumor cells were viably enriched twice
      by MS+/RS+ positive separation column. Parts of the cells from the patients were
      stained with CK-FITC, DAPI and EB. Then, morphology of the stained tumor cells
      was observed under fluorescence microscope. RESULTS: Six hundred and eighty eight
      CK positive cells in 18 cases (45%) were detected, including 384 (55.8%) medium
      sized cells, 102 (14.8%) large-sized cells, 46(6.7%) stem-cell-like cells, 8
      (1.2%) M-phase cells, 84 (12.2%) nuclear debris and 64 (9.3%) non-nuclear debris.
      The number of tumor cells in BM was significantly correlated with TNM stage
      (p=0.038), but not with gender, age, histological differentiation and lymph node
      metastasis. CONCLUSIONS: The DTCs in BM of patients with gastric cancer show
      various morphological characteristics. The existence of these tumor cells
      suggests a poor prognosis.

PMID- 22951526
TI  - Harvesting solar energy by means of charge-separating nanocrystals and their
      solids.
AB  - Conjoining different semiconductor materials in a single nano-composite provides
      synthetic means for the development of novel optoelectronic materials offering a
      superior control over the spatial distribution of charge carriers across material
      interfaces. As this study demonstrates, a combination of donor-acceptor
      nanocrystal (NC) domains in a single nanoparticle can lead to the realization of
      efficient photocatalytic materials, while a layered assembly of donor- and
      acceptor-like nanocrystals films gives rise to photovoltaic materials. Initially
      the paper focuses on the synthesis of composite inorganic nanocrystals,
      comprising linearly stacked ZnSe, CdS, and Pt domains, which jointly promote
      photoinduced charge separation. These structures are used in aqueous solutions
      for the photocatalysis of water under solar radiation, resulting in the
      production of H2 gas. To enhance the photoinduced separation of charges, a
      nanorod morphology with a linear gradient originating from an intrinsic electric
      field is used. The inter-domain energetics are then optimized to drive
      photogenerated electrons toward the Pt catalytic site while expelling the holes
      to the surface of ZnSe domains for sacrificial regeneration (via methanol). Here
      we show that the only efficient way to produce hydrogen is to use electron
      donating ligands to passivate the surface states by tuning the energy level
      alignment at the semiconductor-ligand interface. Stable and efficient reduction
      of water is allowed by these ligands due to the fact that they fill vacancies in
      the valence band of the semiconductor domain, preventing energetic holes from
      degrading it. Specifically, we show that the energy of the hole is transferred to
      the ligand moiety, leaving the semiconductor domain functional. This enables us
      to return the entire nanocrystal-ligand system to a functional state, when the
      ligands are degraded, by simply adding fresh ligands to the system. To promote a
      photovoltaic charge separation, we use a composite two-layer solid of PbS and
      TiO2 films. In this configuration, photoinduced electrons are injected into TiO2
      and are subsequently picked up by an FTO electrode, while holes are channeled to
      a Au electrode via PbS layer. To develop the latter we introduce a Semiconductor
      Matrix Encapsulated Nanocrystal Arrays (SMENA) strategy, which allows bonding PbS
      NCs into the surrounding matrix of CdS semiconductor. As a result, fabricated
      solids exhibit excellent thermal stability, attributed to the heteroepitaxial
      structure of nanocrystal-matrix interfaces, and show compelling light-harvesting
      performance in prototype solar cells.

PMID- 22951527
TI  - Intensified peginterferon alpha-2a dosing increases sustained virologic response
      rates in heavy, high viral load hepatitis C genotype 1 patients with high low
      density lipoprotein.
AB  - BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated
      low-density lipoprotein (LDL) levels achieve higher sustained virologic response
      (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with
      lower LDL. Our aim was to determine whether SVR rates in patients with
      low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS,
      genotype 1 patients with baseline HCV RNA >= 400,000 IU/mL and body weight >= 85
      kg were randomized to 48 weeks of 180 ug/wk PegIFN alpha-2a (40 kDa) plus
      ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 ug/wk PegIFN alpha
      2a followed by 36 weeks of 180 ug/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600
      mg/d). This retrospective analysis assessed SVR rates among patients with low
      (<100 mg/dL) or elevated (>= 100 mg/dL) LDL. Patients with high LDL (n=256) had
      higher baseline HCV RNA (5.86 * 10(6) IU/mL) versus patients with low LDL (n=262;
      4.02 * 10(6) IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis
      identified a significant interaction between PegIFN alpha-2a dose and LDL levels
      on SVR (P=0.0193). The only treatment-related SVR predictor in the nested
      multiple logistic regression was PegIFN alpha-2a dose among patients with
      elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction
      (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and
      35% in the standard and induction-dose groups, respectively; SVR rates in
      patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS:
      Intensified dosing of PegIFN alpha-2a increases SVR rates in patients with
      elevated LDL even with the difficult-to-cure characteristics of genotype 1, high
      baseline viral load, and high body weight.

PMID- 22951528
TI  - Magnetic resonance imaging changes in the size and shape of the oropharynx
      following acute whiplash injury.
AB  - STUDY DESIGN: Prospective longitudinal. OBJECTIVE: To quantify the temporal
      development of magnetic resonance imaging changes in oropharyngeal morphometry in
      subjects with varying levels of disability following a whiplash injury.
      BACKGROUND: A recent cross-sectional investigation has identified reductions in
      the size and shape of the oropharynx in subjects with chronic whiplash-related
      disability when compared to healthy controls. The temporal development of such
      changes and their relationship to persistent disability have yet to be
      investigated. METHODS: Forty-one subjects (30 women) with acute whiplash injury
      were included. Repeated measures T1-weighted magnetic resonance imaging was used
      to measure and compare cross-sectional area (CSA) in square millimeters and shape
      ratio (SR) of the oropharynx at 4 weeks, 3 months, and 6 months postinjury.
      Subjects were classified at 6 months by their Neck Disability Index scores into
      the following categories: recovered (less than 8%), mild disability (10%-28%),
      and moderate/severe disability (greater than 30%). The effects of time and group
      and the interaction effect of group by time on oropharynx morphometry (CSA, SR)
      were investigated using repeated-measures, linear, mixed-model analysis. Based on
      previous research findings, age, gender, and body mass index were entered into
      the analyses as covariates. Where significant main or interaction effects were
      detected, pairwise comparisons were performed to investigate specific differences
      in the dependent variable between groups and within groups over time. RESULTS:
      There was a significant interaction effect for group by time for both the CSA and
      SR values. Age significantly influenced SR (P = .024) and body mass index
      significantly influenced CSA (P = .001). There was no difference in CSA or SR
      across all groups at 4 weeks postinjury. However, at 6 months, CSA was
      significantly different between the recovered group and the moderate/severe group
      (P = .001). The recovered group demonstrated a significant increase in CSA (P =
      .04) over time, whereas the moderate/severe group significantly decreased (P =
      .01). At 6 months, the moderate/severe group had a reduced SR compared to the
      mild group (P = .03). No differences in CSA or SR of the oropharynx were found
      between the mild and recovered groups throughout the study. CONCLUSION: Temporal
      reductions in CSA of the oropharynx occur following whiplash and persist to a
      greater extent in those with moderate/severe symptoms at 6 months postinjury.
      Studies are planned (1) to better investigate the underlying mechanisms of CSA
      reductions, (2) to determine their relevance to functional recovery and
      production of voice following whiplash, and (3) to evaluate multidisciplinary
      assessment and management of these patients.

PMID- 22951529
TI  - Capacitive immunoaffinity biosensor based on vertically paired ring-electrodes.
AB  - A capacitive biosensor was developed by using a vertically paired ring-electrode
      for the non-labeled immunoassay. The vertically paired ring-electrode was
      prepared by sequential deposition and etching processes. Two electrodes were
      layered on glass substrate by sputtering of gold layers with thicknesses of 50 nm
      and 100 nm, and a parylene-C film with a thickness of 550 nm was positioned
      between the electrode layers as a dielectric material by thermal deposition. The
      top layer was made by spin coating of SU-8. And then, the ring-electrodes were
      exposed at the wall of the layered structure by sequential etching processes. The
      fabricated electrodes were characterized by cyclic voltammetry of a well-known
      redox couple of 3,3',5,5'-tetramethylbenzidine. The non-labeled detection of
      antigen-antibody interaction was demonstrated by using anti-horseradish
      peroxidase (HRP) antibodies and C-reactive protein (CRP) as model analytes. When
      the model analytes were bound to the vertically paired ring-electrode, the
      impedance change was measured during the immunoassay steps, and the measured
      impedance was analyzed by using a model circuit of the ring-electrode, and the
      capacitance was estimated to be dependent on the adsorption of analytes between
      the ring-electrodes.

PMID- 22951530
TI  - Real-time label-free immunoassay of interferon-gamma and prostate-specific
      antigen using a Fiber-Optic Localized Surface Plasmon Resonance sensor.
AB  - A Fiber-Optic Localized Surface Plasmon Resonance (FO LSPR) sensor was fabricated
      using spherical gold nanoparticles (Au NPs) on a flattened end-face of the
      optical fiber. The Au NPs were easily synthesized by the Turkevich method and
      were immobilized on the end-face of the optical fiber by using a self-assembled
      monolayer (SAM). In order to examine the possibility of its application as a
      biosensor for label-free immunoassays, the fabricated FO LSPR sensor was used for
      the detection of the antibody-antigen reaction of interferon-gamma (IFN-gamma)
      and the limit of detection (LOD) was approximately 2pg/ml. Herein, The antibodies
      and bovine serum albumins (BSAs) were immobilized on the Au NPs by physisorption.
      Also, the FO LSPR sensor was used for the detection of a prostate-specific
      antigen (PSA) and the LOD was 1pg/ml below. The fabricated FO LSPR sensor can be
      used for real-time label-free immunoassay having fast detection time, high
      resolution and sensitivity. In addition, the proposed sensor platform has the
      advantages of low cost, simple optical setup, remote sensing, simple fabrication,
      real-time detection, low sample volume, and potential application to in-vivo
      detection systems.

PMID- 22951531
TI  - A sub-picogram sensitive rapid chemiluminescent immunoassay for the detection of
      human fetuin A.
AB  - A sub-picogram sensitive chemiluminescent immunoassay (CIA) was developed for the
      detection of human fetuin A (HFA), a specific biomarker for hepatocellular
      carcinoma and atherosclerosis. The anti-HFA antibody was covalently bound to 3
      aminopropyltriethoxysilane-functionalized 96-well chemiluminescent microtiter
      plates (MTP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride
      and N-hydroxysulfosuccinimide. The developed CIA detected HFA in the range of 0.3
      pg mL(-1)-20 ng mL(-1) with an analytical sensitivity of 5 pg mL(-1), which was
      125-fold more sensitive than that of commercial enzyme linked immunosorbent assay
      (ELISA). It is the most sensitive immunoassay for HFA detection. The overall
      immunoassay duration was reduced significantly by more than 3-fold in comparison
      to that of commercial ELISA. The anti-HFA antibody-bound MTPs, stored at 4
      degrees C in 0.1M PBS, were highly stable and did not show any significant
      decrease in functional activity for six months. The perfect correlation between
      the developed CIA and commercial ELISA for the detection of various
      concentrations of HFA spiked in diluted human plasma further demonstrates the
      potential utility of the developed HFA CIA for clinical diagnosis.

PMID- 22951532
TI  - Real-time monitoring of ischemia inside stomach.
AB  - The low pH in the gastric juice of the stomach makes it difficult to fabricate
      stable and functional all-solid-state pH ISE sensors to sense ischemia, mainly
      because of anion interference and adhesion problem between the ISE membrane and
      the electrode surface. In this work, the adhesion of ISE membrane on solid
      surface at low pH was improved by modifying the surface with a conductive
      substrate containing hydrophilic and hydrophobic groups. This creates a stable
      and robust candidate for low pH applications. Moreover, anion interference
      problem at low pH was solved by integration of all-solid-state ISE and internal
      reference electrodes on an array. So, the same tendencies of anion interferences
      for all-solid-state ISE and all-solid-state reference electrodes cancel each
      other in differential potentiometric detection. The developed sensor presents a
      novel all-solid-state potentiometric, miniaturized and mass producible pH ISE
      sensor for detecting ischemia on the stomach tissue on an array designed for
      endoscopic applications.

PMID- 22951533
TI  - Parasite induced genetically driven autoimmune Chagas heart disease in the
      chicken model.
AB  - The Trypanosoma cruzi acute infections acquired in infancy and childhood seem
      asymptomatic, but approximately one third of the chronically infected cases show
      Chagas disease up to three decades or later. Autoimmunity and parasite
      persistence are competing theories to explain the pathogenesis of Chagas disease.
      To separate roles played by parasite persistence and autoimmunity in Chagas
      disease we inoculate the T. cruzi in the air chamber of fertilized eggs. The
      mature chicken immune system is a tight biological barrier against T. cruzi and
      the infection is eradicated upon development of its immune system by the end of
      the first week of growth. The chicks are parasite-free at hatching, but they
      retain integrated parasite mitochondrial kinetoplast DNA (kDNA) minicircle within
      their genome that are transferred to their progeny. Documentation of the kDNA
      minicircle integration in the chicken genome was obtained by a targeted prime
      TAIL-PCR, Southern hybridizations, cloning, and sequencing. The kDNA minicircle
      integrations rupture open reading frames for transcription and immune system
      factors, phosphatase (GTPase), adenylate cyclase and phosphorylases (PKC, NF
      Kappa B activator, PI-3K) associated with cell physiology, growth, and
      differentiation, and other gene functions. Severe myocarditis due to rejection of
      target heart fibers by effectors cytotoxic lymphocytes is seen in the kDNA
      mutated chickens, showing an inflammatory cardiomyopathy similar to that seen in
      human Chagas disease. Notably, heart failure and skeletal muscle weakness are
      present in adult chickens with kDNA rupture of the dystrophin gene in chromosome
      1. Similar genotipic alterations are associated with tissue destruction carried
      out by effectors CD45+, CD8gammadelta+, CD8alpha lymphocytes. Thus this protozoan
      infection can induce genetically driven autoimmune disease.

PMID- 22951535
TI  - Images in vascular medicine. Spindle cell sarcoma of the common femoral vein as a
      possible differential for deep venous thrombosis on ultrasound.

PMID- 22951536
TI  - Significant gas uptake enhancement by post-exchange of zinc(II) with copper(II)
      within a metal-organic framework.
AB  - Coordination of a tetratopic nitrogen-rich linker with Zn(2+) under solvothermal
      conditions afforded a Zn-based metal organic framework (MOF), where the Zn(II)
      ions could be exchanged by Cu(II) ions in a single-crystal-to-single-crystal
      fashion leading to a new Cu-based MOF. Such transformation induces a significant
      enhancement in gas sorption along with a high selectivity towards CO(2) over N(2)
      and CH(4).

PMID- 22951537
TI  - The effects of thoracic spine manipulation in subjects with signs of rotator cuff
      tendinopathy.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To assess scapular
      kinematics and electromyographic signal amplitude of the shoulder musculature,
      before and after thoracic spine manipulation (TSM) in subjects with rotator cuff
      tendinopathy (RCT). Changes in range of motion, pain, and function were also
      assessed. BACKGROUND: There are various treatment techniques for RCT. Recent
      studies suggest that TSM may be a useful component in the management of pain and
      dysfunction associated with RCT. METHODS: Thirty subjects between 18 and 45 years
      of age, who showed signs of RCT, participated in this study. Changes in scapular
      kinematics and muscle activity, as well as changes in shoulder pain and function,
      were assessed pre-TSM and post-TSM using paired t tests and repeated-measures
      analyses of variance. RESULTS: TSM did not lead to changes in range of motion or
      scapular kinematics, with the exception of a small decrease in scapular upward
      rotation (P = .05). The only change in muscle activity was a small but
      significant increase in middle trapezius activity (P = .03). After TSM, subjects
      demonstrated decreased pain during performance of the Jobe empty-can (mean +/- SD
      change, 2.6 +/- 1.1), Neer (2.6 +/- 1.3), and Hawkins-Kennedy (2.8 +/- 1.3) tests
      (all, P<.001). Subjects also reported decreased pain with shoulder flexion (mean
      +/- SD change, 2.0 +/- 1.5; P<.001) and improved shoulder function (force
      production, 2.5 +/- 1.4 kg; Penn Shoulder Score, 7.7 +/- 9.4; sports/performing
      arts module of the Disabilities of the Arm, Shoulder and Hand questionnaire, 16.4
      +/- 13.2) (all, P<.001). CONCLUSION: Immediate improvements in shoulder pain and
      function post-TSM are not likely explained by alterations in scapular kinematics
      or shoulder muscle activity. For people with pain associated with RCT, TSM may be
      an effective component of their treatment plan to improve pain and function.
      However, further randomized controlled studies are necessary to better validate
      this treatment approach. LEVEL OF EVIDENCE: Therapy, level 4.

PMID- 22951538
TI  - Supine proton beam craniospinal radiotherapy using a novel tabletop adapter.
AB  - To develop a device that allows supine craniospinal proton and photon therapy to
      the vast majority of proton and photon facilities currently experiencing
      limitations as a result of couch design issues. Plywood and carbon fiber were
      used for the development of a prototype unit. Once this was found to be
      satisfactory after all design issues were addressed, computer-assisted design
      (CAD) was used and carbon fiber tables were built to our specifications at a
      local manufacturer of military and racing car carbon fiber parts. Clinic-driven
      design was done using real-time team discussion for a prototype design. A local
      machinist was able to construct a prototype unit for us in <2 weeks after the
      start of our project. Once the prototype had been used successfully for several
      months and all development issues were addressed, a custom carbon fiber design
      was developed in coordination with a carbon fiber manufacturer in partnership.
      CAD methods were used to design the units to allow oblique fields from head to
      thigh on patients up to 200 cm in height. Two custom-designed carbon fiber
      craniospinal tabletop designs now exist: one long and one short. Four are in
      successful use in our facility. Their weight tolerance is greater than that of
      our robot table joint (164 kg). The long unit allows for working with taller
      patients and can be converted into a short unit as needed. An affordable,
      practical means of doing supine craniospinal therapy with protons or photons can
      be used in most locations via the use of these devices. This is important because
      proton therapy provides a much lower integral dose than all other therapy methods
      for these patients and the supine position is easier for patients to tolerate and
      for anesthesia delivery. These units have been successfully used for adult and
      pediatric supine craniospinal therapy, proton therapy using oblique beams to the
      low pelvis, treatment of various spine tumors, and breast-sparing Hodgkin's
      therapy.

PMID- 22951539
TI  - Chronological and replicative lifespan in yeast: do they meet in the middle?

PMID- 22951540
TI  - A role for protein phosphatase 4 in regulating non-homologous end-joining.

PMID- 22951541
TI  - Cyclin D1 goes metabolic: dual functions of cyclin D1 in regulating lipogenesis.

PMID- 22951542
TI  - Acetic acid and acidification accelerate chronological and replicative aging in
      yeast.

PMID- 22951543
TI  - Floral-clustered few-layer graphene nanosheet array as high performance field
      emitter.
AB  - Graphene sheet is expected to be a highly efficient field emitter due to its
      unique electrical properties and open surface with sharp edges. However, it is
      still a tremendous technical challenge to grow and align a graphene sheet in one
      particular direction to protrude its sharp edges for good field emission. Here,
      we report an ideal graphene field emitter of flower-like graphene nanosheets
      grown on a silicon nanocone array, wherein nanocone array guides the alignment of
      vertical nanosheets and produces high-density sharp edge protrusions on the
      conical tip. We observe high performance and stable field emission with low turn
      on fields from floral-clustered graphene nanosheets. Protrusive sharp edges on
      the nanocone tip and optimized spacing between clusters both appear to locally
      enhance the electric field and dramatically increase field emission. Our new
      graphene emitter design provides a robust approach to the prospect for
      development of practical electron sources and advanced devices based on graphene
      field emitters.

PMID- 22951544
TI  - Induction of graft-versus-host disease and in vivo T cell monitoring using an MHC
      matched murine model.
AB  - Graft-versus-host disease (GVHD) is the limiting barrier to the broad use of bone
      marrow transplant as a curative therapy for a variety of hematological
      deficiencies. GVHD is caused by mature alloreactive T cells present in the bone
      marrow graft that are infused into the recipient and cause damage to host organs.
      However, in mice, T cells must be added to the bone marrow inoculum to cause
      GVHD. Although extensive work has been done to characterize T cell responses post
      transplant, bioluminescent imaging technology is a non-invasive method to monitor
      T cell trafficking patterns in vivo. Following lethal irradiation, recipient mice
      are transplanted with bone marrow cells and splenocytes from donor mice. T cell
      subsets from L2G85.B6 (transgenic mice that constitutively express luciferase)
      are included in the transplant. By only transplanting certain T cell subsets, one
      is able to track specific T cell subsets in vivo, and based on their location,
      develop hypotheses regarding the role of specific T cell subsets in promoting
      GVHD at various time points. At predetermined intervals post transplant,
      recipient mice are imaged using a Xenogen IVIS CCD camera. Light intensity can be
      quantified using Living Image software to generate a pseudo-color image based on
      photon intensity (red = high intensity, violet = low intensity). Between 4-7 days
      post transplant, recipient mice begin to show clinical signs of GVHD. Cooke et
      al. developed a scoring system to quantitate disease progression based on the
      recipient mice fur texture, skin integrity, activity, weight loss, and posture.
      Mice are scored daily, and euthanized when they become moribund. Recipient mice
      generally become moribund 20-30 days post transplant. Murine models are valuable
      tools for studying the immunology of GVHD. Selectively transplanting particular T
      cell subsets allows for careful identification of the roles each subset plays.
      Non-invasively tracking T cell responses in vivo adds another layer of value to
      murine GVHD models.

PMID- 22951545
TI  - A planar chiral [2.2]paracyclophane derived N-heterocyclic stannylene.
AB  - The reaction of pseudo-ortho-4,12-N,N'-diphenyldiamino-[2.2]paracyclophane ((+/-)
      3) with Sn[N(SiMe(3))(2)](2) results in the formation of the monomeric planar
      chiral N-heterocyclic stannylene (+/-)-4, featuring a unique [2.2]paracyclophane
      backbone, which has been characterized by an X-ray diffraction study.

PMID- 22951546
TI  - Consort 2010 statement: extension to cluster randomised trials.

PMID- 22951547
TI  - Teaching postgraduates about managing drug and alcohol misuse.

PMID- 22951548
TI  - Irritable bowel syndrome.

PMID- 22951549
TI  - Increased risk of preterm birth after treatment for CIN.

PMID- 22951550
TI  - Evidence of net benefit of proton pump inhibitors with clopidogrel is lacking in
      older patients.

PMID- 22951552
TI  - Bigger margins are not better in breast conserving surgery.

PMID- 22951553
TI  - Cleaning up joint replacement services in the UK.

PMID- 22951554
TI  - National early warning score (NEWS) is not suitable for all patients.

PMID- 22951555
TI  - Treat all cases of cellulitis with anti-staphylococcal antibiotics.

PMID- 22951556
TI  - Fungal infection, not diabetes, is risk factor for cellulitis.

PMID- 22951557
TI  - Co-trimoxazole is useful in community acquired MRSA cellulitis.

PMID- 22951558
TI  - Drug development: Innovation or imitation deficit?

PMID- 22951560
TI  - Opportunistic or population register based programmes for chlamydia screening?

PMID- 22951561
TI  - What's in a name?

PMID- 22951562
TI  - How times have changed.

PMID- 22951563
TI  - Teenagers and newborn babies in England and Wales may get pertussis jab as cases
      continue to rise.

PMID- 22951564
TI  - Paying hospitals for all patients' visits increases activity without necessarily
      improving quality, report shows.

PMID- 22951565
TI  - Why do we overtreat hypertension?

PMID- 22951566
TI  - Thalidomide manufacturer offers apology but no compensation.

PMID- 22951567
TI  - Length of hospital stay for hip fracture falls by a day, audit shows.

PMID- 22951568
TI  - Plaque assay for murine norovirus.
AB  - Murine norovirus (MNV) is the only member of the Norovirus genus that efficiently
      grows in tissue culture. Cell lysis and cytopathic effect (CPE) are observed
      during MNV-1 infection of murine dendritic cells or macrophages. This property of
      MNV-1 can be used to quantify the number of infectious particles in a given
      sample by performing a plaque assay. The plaque assay relies on the ability of
      MNV-1 to lyse cells and to form holes in a confluent cell monolayer, which are
      called plaques. Multiple techniques can be used to detect viral infections in
      tissue culture, harvested tissue, clinical, and environmental samples, but not
      all measure the number of infectious particles (e.g. qRT-PCR). One way to
      quantify infectious viral particles is to perform a plaque assay, which will be
      described in detail below. A variation on the MNV plaque assay is the fluorescent
      focus assay, where MNV antigen is immunostained in cell monolayers. This assay
      can be faster, since viral antigen expression precedes plaque formation. It is
      also useful for titrating viruses unable to form plaques. However, the
      fluorescent focus assay requires additional resources beyond those of the plaque
      assay, such as antibodies and a microscope to count focus-forming units.
      Infectious MNV can also be quantified by determining the 50% Tissue Culture
      Infective Dose (TCID50). This assay measures the amount of virus required to
      produce CPE in 50% of inoculated tissue culture cells by endpoint titration.
      However, its limit of detection is higher compared to a plaque assay. In this
      article, we describe a plaque assay protocol that can be used to effectively
      determine the number of infectious MNV particles present in biological or
      environmental samples. This method is based on the preparation of 10-fold serial
      dilutions of MNV-containing samples, which are used to inoculate a monolayer of
      permissive cells (RAW 264.7 murine macrophage cells). Virus is allowed to attach
      to the cell monolayer for a given period of time and then aspirated before
      covering cells with a mixture of agarose and cell culture media. The agar enables
      the spread of viral progeny to neighboring cells while limiting spread to
      distantly located cells. Consequently, infected cells are lysed and form holes in
      the monolayer known as plaques. Upon sufficient spread of virus, plaques become
      visible following staining of cells with dyes, like neutral red, methylene blue,
      or crystal violet. At low dilutions, each plaque originates from one infectious
      viral particle and its progeny, which spread to neighboring cells. Thus, counting
      the number of plaques allows one to calculate plaque-forming units (PFU) present
      in the undiluted sample.

PMID- 22951569
TI  - Anatase-rutile phase transformation of titanium dioxide bulk material: a DFT + U
      approach.
AB  - The anatase-rutile phase transformation of TiO(2) bulk material is investigated
      using a density functional theory (DFT) approach in this study. According to the
      calculations employing the Perdew-Burke-Ernzerhof (PBE) exchange-correlation
      functional with the Vanderbilt ultrasoft pseudopotential, it is suggested that
      the anatase phase is more energetically stable than rutile, which is in variance
      with the experimental observations. Consequently, the DFT + U method is employed
      in order to predict the correct structural stability in titania from electronic
      structure-based total energy calculations. The Hubbard U term is determined by
      examining the band structure of rutile with various values of U from 3 to 10 eV.
      At U = 5 eV, a theoretical bandgap for rutile is obtained as 3.12 eV, which is in
      very good agreement with the reported experimental bandgap. Hence, we choose the
      DFT + U method (with U = 5 eV) to investigate the transformation pathway using
      the newly-developed solid-state nudged elastic band (ss-NEB) method, and
      consequently obtain an intermediate transition structure that is 9.794 eV per
      four-TiO(2) above the anatase phase. When the Ti-O bonds in the transition state
      are examined using charge density analysis, seven Ti-O bonds (out of 24 bonds in
      the anatase unit cell) are broken, and this result is in excellent agreement with
      a previous experimental study (Penn and Banfield 1999 Am. Miner. 84 871-6).

PMID- 22951570
TI  - Construction of recombinant adenovirus vector with connexin 43 gene.

PMID- 22951571
TI  - A sport physiotherapist as medical director: taking a leadership role.
AB  - According to Wikipedia, a medical director is typically a physician who provides
      healthcare guidance, leadership,oversight, and quality assurance. The medical
      director is responsible for creating treatment protocols and providing oversight
      for all constituents who deliver healthcare services to a particular target
      population. There are, however, significant variations from country to country
      regarding the role and responsibilities of the medical director. The author
      discusses his experience as a sports physiotherapist in the medical director
      position for the Israel Football Association.

PMID- 22951572
TI  - Effectiveness of an exposure-based return-to-work program for workers on sick
      leave due to common mental disorders: a cluster-randomized controlled trial.
AB  - OBJECTIVES: In case of long-term sick leave, gradually increasing workload
      appears to be an effective component of work-directed interventions to reduce
      sick leave due to common mental disorders (CMD). CMD are defined as stress
      related, adjustment, anxiety, or depressive disorders. We developed an exposure
      based return-to-work (RTW-E) intervention and evaluated the effect on time-to
      full return to work (RTW) among workers who were on sick leave due to CMD in
      comparison to those treated with care-as-usual (CAU). CAU is guideline-directed
      and consists of problem-solving strategies and graded activities. METHODS: Using
      a two-armed cluster-randomized trial, we randomized 56 occupational physicians
      (OP). Of these, 35 OP treated 160 workers at the start of their sick leave; 75
      workers received RTW-E and 85 workers received CAU. These workers were followed
      over a 12-month follow-up period. The time-to-full RTW lasting >=28 days without
      recurrence was the primary outcome measure. To evaluate differences between
      groups, we used intention-to-treat and multilevel Cox's regression analysis.
      RESULTS: The median time-to-full RTW differed significantly between groups
      [hazard ratio (HR) 0.55; 95% confidence interval (95% CI) 0.33-0.89]. The workers
      receiving RTW-E (209 days; 95% CI 62-256) had a prolonged time-to-full RTW
      compared to workers receiving CAU (153 days; 95% CI 128-178). CONCLUSIONS:
      Workers on sick leave due to CMD treated with RTW-E showed a prolonged time-to
      full RTW compared to those treated with CAU. We recommend that OP do not apply
      RTW-E but continue counseling workers on sick leave due to CMD according to CAU.

PMID- 22951573
TI  - A new technology for recycling solder from waste printed circuit boards using
      ionic liquid.
AB  - Waste printed circuit boards (WPCBs) contain lots of valuable resources together
      with plenty of hazardous materials, which are considered both an attractive
      secondary resource and an environmental contaminant. In this study, a new
      technology for the recovery of solder from WPCBs using an ionic liquid of 1-ethyl
      3-methylimizadolium tetrafluoroborate ([EMIM(+)][BF(4)(-)]) as a heating medium
      was investigated. Experimental results indicate that the separation of solder
      from WPCBs is complete when WPCBs are heated at 240  degrees C and
      [EMIM(+)][BF(4)(-)] is stirred at 150 rpm for 10 min. By observing the cross
      sections of WPCBs before and after treatment with the ionic liquid, it has been
      found that there is a initial delaminating phenomenon for WPCBs, which implies
      that [EMIM(+)][BF(4)(-)] can dissolve bromine epoxy resins of WPCBs to some
      extent. This clean and non-polluting technology offers a new way of recycling
      valuable materials from WPCBs and prevents the environmental pollution by WPCBs
      effectively.

PMID- 22951574
TI  - Using a Multi-Locus Microsatellite Typing method improved phylogenetic
      distribution of Candida albicans isolates but failed to demonstrate association
      of some genotype with the commensal or clinical origin of the isolates.
AB  - The dimorphic yeast Candida albicans is a component of the normal microflora at
      the mucosal surfaces of healthy individuals. It possesses an array of phenotypic
      properties considered as virulence traits that contribute to pathogenicity of the
      yeast in immuno-compromised patients. We addressed the question of the
      pathogenicity of lineages of C. albicans with regard to their genotype in three
      series of C. albicans isolates (a series of commensal isolates collected in
      healthy individuals, a group of bloodstream isolates and a group of non
      bloodstream clinical isolates) using a Multi-Locus Microsatellite Typing (MLMT)
      approach based on the analysis of the polymorphism of 11 microsatellite loci. The
      MLMT analysis of the three series, corresponding to 174 C. albicans isolates,
      gave a 100% typability to the method, with a DP index of 0.999. The UPGMA
      analysis showed that the isolates segregated in eight phylogenetic groups.
      Interestingly, the clustering was comparable when using NJ and MS-tree algorithms
      and a good concordance index of the clustering was observed with MLST. All in all
      our data strongly indicated MLMT as a reliable tool for DNA-typing studies in C.
      albicans. Isolates from healthy and non-healthy individuals segregated at the
      same proportions into the eight phylogenetic groups, suggesting that isolates of
      different origin share the same overall pathogenicity. Surprisingly allelic
      frequencies at the HIS3 microsatellite differed significantly in commensal
      isolates (group A) from pooled groups B and C (clinical isolates), raising the
      possibility that some individual alleles at the HIS3 microsatellite may be
      associated with distinct pathogenic profiles in C. albicans.

PMID- 22951575
TI  - Genetic characterization and codon usage bias of full-length Hepatitis E virus
      sequences shed new lights on genotypic distribution, host restriction and genome
      evolution.
AB  - Hepatitis E virus (HEV) is present in different species and ecological niches. It
      has been divided into 4 major mammalian genotypes. In this study, 3 new full
      length genomes of swine HEV were sequenced and the results did not reveal any
      particular host determinant in comparison with human isolates belonging to the
      same genotype. Nucleotide composition and codon usage bias were determined to
      characterize HEV host restriction and genome evolution. Peculiar nucleotide bias
      was observed for A and C nucleotides in all HEV genotypes. Apart from the ORF1
      hypervariable region and the ORF2/3 overlapping region, no nucleotide bias was
      observed between the 3 codon positions. CpG dinucleotides were also shown to be
      under-represented in HEV as in most RNA viruses. The effective number of codon
      used in HEV genome was high, indicating a lack of codon bias. Correspondence
      analysis of the relative synonymous codon usage was performed and demonstrated
      that evolution of HEV is not driven by geographical or host factors, but is
      representative of HEV phylogeny. These results confirm that HEV genome evolution
      is mainly based on mutational pressure. Natural selection, for instance involving
      fine-tuning translation kinetics and escape from the host immune system, may also
      play a role in shaping the HEV genome, particularly in the ORF1 hypervariable
      region and the ORF2/3 overlapping region. These regions might be involved in host
      restriction. Finally this study revealed the need to re-evaluate the possible
      subtyping classification.

PMID- 22951576
TI  - Image of acupuncture.

PMID- 22951577
TI  - Group acupuncture for osteoarthritis; a practical option?

PMID- 22951578
TI  - Enhancement of visible-light-driven photoresponse of Mn/ZnO system:
      photogenerated charge transfer properties and photocatalytic activity.
AB  - A visible-light-active ZnO photocatalyst system in the presence of manganese ions
      (Mn/ZnO) was prepared via a simple and rapid approach. XRD, XPS, Raman scattering
      and UV-Vis DRS confirmed the manganese exists in multivalent forms
      (Mn(3+)/Mn(2+)) in the ZnO lattice, furthermore, ZnO light absorption is extended
      to the visible region. The photocatalytic activities of the catalysts were
      evaluated by measuring the photodegrading efficiency of 2,4-dichlorophenol (DCP)
      under visible light irradiation. With an optimal molar ratio of 5% in Mn/ZnO the
      highest rate photodegradation was achieved under the experimental conditions. We
      have characterized the separation and transfer behavior of the photogenerated
      charges in the visible region by means of surface photovoltage (SPV), surface
      photocurrent (SPC) and transient photovoltage (TPV) techniques. Based on the
      comprehensive investigation of the photovoltaic properties of Mn/ZnO
      photocatalyst, we illustrate the behavior of photogenerated charges have distinct
      effects on the photocatalytic activity. It is demonstrated that the incorporation
      of multivalent Mn in ZnO promoted the separation of photogenerated charges,
      inhibited the recombination of photogenerated carriers, and thus prolonged the
      charges lifetime to participate in the photocatalytic reaction, resulting in
      highly efficient photocatalytic activity, which is attributed to the formation of
      a strong electronic interaction between the multivalent Mn and ZnO.

PMID- 22951579
TI  - Noninvasive functionalization of polymers of intrinsic microporosity for enhanced
      CO2 capture.
AB  - Modifying sorbents for the purpose of improving carbon dioxide capture often
      results in the loss of surface area or accessible pores, or both. We report the
      first noninvasive functionalization of the polymers of intrinsic microporosity
      (PIMs) where inclusion of the amidoxime functionality in PIM-1 increases carbon
      dioxide capacity up to 17% and micropore surface area by 20% without losing its
      film forming ability.

PMID- 22951580
TI  - Protocol for long duration whole body hyperthermia in mice.
AB  - Hyperthermia is a general term used to define the increase in core body
      temperature above normal. It is often used to describe the increased core body
      temperature that is observed during fever. The use of hyperthermia as an adjuvant
      has emerged as a promising procedure for tumor regression in the field of cancer
      biology. For this purpose, the most important requirement is to have reliable and
      uniform heating protocols. We have developed a protocol for hyperthermia (whole
      body) in mice. In this protocol, animals are exposed to cycles of hyperthermia
      for 90 min followed by a rest period of 15 min. During this period mice have easy
      access to food and water. High body temperature spikes in the mice during first
      few hyperthermia exposure cycles are prevented by immobilizing the animal.
      Additionally, normal saline is administered in first few cycles to minimize the
      effects of dehydration. This protocol can simulate fever like conditions in mice
      up to 12-24 hr. We have used 8-12 weeks old BALB/Cj female mice to demonstrate
      the protocol.

PMID- 22951581
TI  - Functional roles of pluripotency transcription factors in mesenchymal stem cells.

PMID- 22951582
TI  - Magnetic field tuning of polaron losses in Fe doped BaTiO3 single crystals.
AB  - Artificial tuning of dielectric parameters can result from interface conductivity
      in polycrystalline materials. In ferroelectric single crystals, it has already
      been shown that ferroelectric domain walls can be the source of such artificial
      coupling. We show here that low-temperature dielectric losses can be tuned by a
      dc magnetic field. Since such losses were previously ascribed to polaron
      relaxation we suggest this results from the interaction of hopping polarons with
      the magnetic field. The fact that this loss alteration has no counterpart in the
      real part of the dielectric permittivity confirms that no interface is involved
      in this purely dynamical effect. The contribution of mobile charges hopping among
      Fe-related centers was confirmed by ESR spectroscopy, showing a maximum intensity
      at ca T ~ 40 K.

PMID- 22951583
TI  - Trapping {BW12}2 tungstoborate: synthesis and crystal structure of hybrid
      [{(H2BW12O42)2O}{Mo6O6S6(OH)4(H2O)2}]14- anion.
AB  - Reaction between monolacunary {BW(11)} tungstoborate and oxothiocationic building
      block, {Mo(2)O(2)S(2)}, results in the formation of a new polyoxothiometalate
      with a unique architecture in which two [H(2)BW(12)O(43)](9-) tungstoborate
      subunits are linked together with a hexamolybdate
      [Mo(V)(6)O(6)S(6)(OH)(4)(H(2)O)(2)](2+) bridge.

PMID- 22951584
TI  - Transcriptional profiling of the parr-smolt transformation in Atlantic salmon.
AB  - The parr-smolt transformation in Atlantic salmon (Salmo salar) is a complex
      developmental process that culminates in the ability to migrate to and live in
      seawater. We used GRASP 16K cDNA microarrays to identify genes that are
      differentially expressed in the liver, gill, hypothalamus, pituitary, and
      olfactory rosettes of smolts compared to parr. Smolts had higher levels of gill
      Na(+)/K(+)-ATPase activity, plasma cortisol and plasma thyroid hormones relative
      to parr. Across all five tissues, stringent microarray analyses identified 48
      features that were differentially expressed in smolts compared to parr. Using a
      less stringent method we found 477 features that were differentially expressed at
      least 1.2-fold in smolts, including 172 features in the gill. Smolts had higher
      mRNA levels of genes involved in transcription, protein biosynthesis and folding,
      electron transport, oxygen transport, and sensory perception and lower mRNA
      levels for genes involved in proteolysis. Quantitative RT-PCR was used to confirm
      differential expression in select genes identified by microarray analyses and to
      quantify expression of other genes known to be involved in smolting. This study
      expands our understanding of the molecular processes that underlie smolting in
      Atlantic salmon and identifies genes for further investigation.

PMID- 22951585
TI  - Dendritic cell-based in vitro assays for vaccine immunogenicity.
AB  - Dendritic cells (DC) are pivotal in the induction of adaptive immune responses
      because they can activate naive T-cells. Moreover, they steer these adaptive
      immune responses by integrating various stimuli, such as from different pathogen
      associated molecular patterns and the cytokine milieu. Immature DC are very well
      capable of ingesting protein antigens, whereas mature DC are efficient presenters
      of peptides to naive T cells. Human DC can be readily cultured from peripheral
      blood mononuclear cells, which are isolated from human blood. There is a strong
      need to monitor in a high-throughput fashion the immunogenicity of candidate
      vaccines during the process of vaccine development. Furthermore, regulators
      require efficacy and safety testing for batch release. For some vaccines, these
      tests require animal testing, causing pain and discomfort, which cannot be
      contested because it would interfere with the test results. With the aims of
      promoting vaccine development and reducing the number of animals for batch
      release testing, we propose to use more broadly human DC for vaccine
      immunogenicity testing. In this commentary, this proposition is illustrated by
      several examples in which the maturation of human DC was successfully used to
      test for vaccine and adjuvant immunogenicity.

PMID- 22951586
TI  - Ping-pong polymerization by allylation and hydroformylation for alternating vinyl
      alcohol-vinyl monomer copolymers.
AB  - Inspired by the enzymatic ping-pong mechanism, we designed a novel "ping-pong
      polymerization", which employs allylation and hydroformylation in an iterative
      and alternating manner. Thus, alternating and regioregular vinyl alcohol-vinyl
      monomer copolymers possessing multiple hydroxy groups in a periodical manner were
      successfully synthesized.

PMID- 22951587
TI  - Calibration of EBT2 film by the PDD method with scanner non-uniformity
      correction.
AB  - The EBT2 film together with a flatbed scanner is a convenient dosimetry QA tool
      for verification of clinical radiotherapy treatments. However, it suffers from a
      relatively high degree of uncertainty and a tedious film calibration process for
      every new lot of films, including cutting the films into several small pieces,
      exposing with different doses, restoring them back and selecting the proper
      region of interest (ROI) for each piece for curve fitting. In this work, we
      present a percentage depth dose (PDD) method that can accurately calibrate the
      EBT2 film together with the scanner non-uniformity correction and provide an easy
      way to perform film dosimetry. All films were scanned before and after the
      irradiation in one of the two homemade 2 mm thick acrylic frames (one portrait
      and the other landscape), which was located at a fixed position on the scan bed
      of an Epson 10 000XL scanner. After the pre-irradiated scan, the film was placed
      parallel to the beam central axis and sandwiched between six polystyrene plates
      (5 cm thick each), followed by irradiation of a 20 * 20 cm2 6 MV photon beam. Two
      different beams on times were used on two different films to deliver a dose to
      the film ranging from 32 to 320 cGy. After the post-irradiated scan, the net
      optical densities for a total of 235 points on the beam central axis on the films
      were auto-extracted and compared with the corresponding depth doses that were
      calculated through the measurement of a 0.6 cc farmer chamber and the related PDD
      table to perform the curve fitting. The portrait film location was selected for
      routine calibration, since the central beam axis on the film is parallel to the
      scanning direction, where non-uniformity correction is not needed (Ferreira et al
      2009 Phys. Med. Biol. 54 1073-85). To perform the scanner non-uniformity
      calibration, the cross-beam profiles of the film were analysed by referencing the
      measured profiles from a ProfilerTM. Finally, to verify our method, the films
      were exposed to 60 degrees  physical wedge fields and the compositive fields, and
      their relative dose profiles were compared with those from the water phantom
      measurement. The fitting uncertainty was less than 0.5% due to the many
      calibration points, and the overall calibration uncertainty was within 3% for
      doses above 50 cGy, when the average of four films were used for the calibration.
      According to our study, the non-uniformity calibration factor was found to be
      independent of the given dose for the EBT2 film and the relative dose differences
      between the profiles measured by the film and the Profiler were within 1.5% after
      applying the non-uniformity correction. For the verification tests, the relative
      dose differences between the measurements by films and in the water phantom, when
      the average of three films were used, were generally within 3% for the 60 degrees
      wedge fields and compositive fields, respectively. In conclusion, our method is
      convenient, time-saving and cost-effective, since no film cutting is needed and
      only two films with two exposures are needed.

PMID- 22951589
TI  - Charge effect of foreign metal ions and the crystal growth process in hybridized
      metal-organic frameworks.
AB  - A paddle-wheel-type Cu metal-organic framework CuHTPO involving hydrogen bonds in
      the network is utilized to obtain composite systems with different metal ions of
      Zn(2+) and Tb(3+). The framework stability and crystal transformation are
      affected by the charges of foreign cations.

PMID- 22951588
TI  - Health-related quality of life among survivors of aggressive non-Hodgkin
      lymphoma.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) is the fifth most common cancer among men
      and women. Patients with aggressive NHL receive intense medical treatments that
      can significantly compromise health-related quality of life (HRQOL). However,
      knowledge of HRQOL and its correlates among survivors of aggressive NHL is
      limited. METHODS: Self-reported data on HRQOL (physical and mental function,
      anxiety, depression, and fatigue) were analyzed for 319 survivors of aggressive
      NHL. Survivors 2 to 5 years postdiagnosis were selected from the Los Angeles
      County Cancer Registry. Bivariate and multivariable methods were used to assess
      the influence of sociodemographic, clinical, and cognitive health-appraisal
      factors on survivors' HRQOL. RESULTS: After accounting for other covariates,
      marital status was associated with all HRQOL outcomes (P < .05). Younger
      survivors reported worse mental function and higher levels of depression,
      anxiety, and fatigue (P < .01). Survivors who had more comorbid conditions or
      lacked private health insurance reported worse physical and mental function and
      higher levels of depression and fatigue (P < .05). Survivors who experienced a
      recurrence reported worse physical function and higher levels of depression and
      fatigue (P < .05). With the exception of a nonsignificant association between
      perceived control and physical function, greater perceptions of personal control
      and health competence were associated significantly with more positive HRQOL
      outcomes (P < .01). CONCLUSIONS: The current results indicated that survivors of
      aggressive NHL who are younger, are unmarried, lack private insurance, or
      experience greater illness burden may be at risk for poorer HRQOL. Cognitive
      health-appraisal factors were strongly related to HRQOL, suggesting potential
      benefits of interventions focused on these mutable factors for this population.

PMID- 22951591
TI  - A novel fluorescent reporter system for monitoring and identifying RNase III
      activity and its target RNAs.
AB  - Bacteriophage vectors for achieving single-copy gene expression linked to a
      colorigenic reporter assay have been used successfully for genetic screening
      applications. However, the limited number of cloning sites in these vectors,
      combined with the requirement for lac- strains and the time- and/or media
      dependence of the chemical-based colorimetric reaction, have limited the range of
      applications for these vectors. An alternative approach using a fluorescent
      reporter gene such as green fluorescent protein (GFP) or GFP derivatives could
      overcome some of these technical issues and facilitate real-time monitoring of
      promoter and/or protein activity. Here, we report the development of a novel
      translational bacteriophage fusion vector encoding enhanced GFP (eGFP) that can
      be incorporated into the chromosome as a single-copy gene. We identified a
      Bacillus promoter (BP) that is stably expressed in Escherichia coli and drives ~6
      fold more expression of eGFP than the T7 promoter in the absence of inducer.
      Incorporating this BP and RNase III target signals into a single system enabled
      clear detection of the absence or downregulation of RNase III activity in vivo,
      thereby establishing a system for screening and identifying novel RNase III
      targets in a matter of days. An RNase III target signal identified in this manner
      was confirmed by post-transcriptional analysis. We anticipate that this novel
      translational fusion vector will be used extensively to study activity of both
      interesting RNases and related complex or to identify or validate targets of
      RNases that are otherwise difficult to study due to their sensitivity to
      environmental stresses and/or autoregulatory processes.

PMID- 22951590
TI  - XenomiRs and miRNA homeostasis in health and disease: evidence that diet and
      dietary miRNAs directly and indirectly influence circulating miRNA profiles.
AB  - Contributions of dietary miRNAs to circulating small RNA profiles would have
      profound implications for interpretation of miRNA biomarker studies: presumptive
      disease-specific markers might instead indicate responses to disease-associated
      quantitative or qualitative dietary alteration. This examination weighs the
      evidence for a 2-fold hypothesis: first, that ingested biological matter
      contributes directly to the miRNA complement of body compartments; and second,
      that these diet-derived exogenous miRNAs (or "xenomiRs") affect total miRNA
      profiles as part of a circulating miRNA homeostasis that is altered in many
      diseases. Homeostasis of high-density lipoprotein (HDL), a known miRNA carrier
      provides a model as a proposed component of broader miRNA homeostasis. Further
      research into the dietary xenomiR hypothesis is needed to ensure rigor in the
      search for truly disease-specific miRNA biomarkers.

PMID- 22951592
TI  - Telomerase caught in the act: united we stand, divided we fall.
AB  - The stable linearity of eukaryotic chromosomes depends on special characteristics
      of their ends, the telomeres. Accurate telomere function in turn requires a
      sustained presence of repeated DNA elements, which are maintained by the enzyme
      telomerase. The telomerase holoenzyme is composed of both protein and RNA, and
      its functions rely on proper expression, maturation, trafficking and assembly of
      these components. Conflicting models for the recruitment of telomerase at
      telomeres have been proposed; one suggests a local activation of telomerase at
      short telomeres, while the other proposes that telomerase is recruited only at
      short telomeres. To discriminate between these models and investigate the cell
      cycle-dependent regulation of telomerase in living cells, a GFP reporter system
      to visualize the yeast telomerase RNA has been recently developed. This assay
      shed new light on the mechanism of recruitment of telomerase to telomeres, and it
      uncovered a hitherto unrecognized mechanism for restricting telomerase access to
      telomeres.

PMID- 22951593
TI  - Terahertz microfluidic sensing using a parallel-plate waveguide sensor.
AB  - Refractive index (RI) sensing is a powerful noninvasive and label-free sensing
      technique for the identification, detection and monitoring of microfluidic
      samples with a wide range of possible sensor designs such as interferometers and
      resonators. Most of the existing RI sensing applications focus on biological
      materials in aqueous solutions in visible and IR frequencies, such as DNA
      hybridization and genome sequencing. At terahertz frequencies, applications
      include quality control, monitoring of industrial processes and sensing and
      detection applications involving nonpolar materials. Several potential designs
      for refractive index sensors in the terahertz regime exist, including photonic
      crystal waveguides, asymmetric split-ring resonators, and photonic band gap
      structures integrated into parallel-plate waveguides. Many of these designs are
      based on optical resonators such as rings or cavities. The resonant frequencies
      of these structures are dependent on the refractive index of the material in or
      around the resonator. By monitoring the shifts in resonant frequency the
      refractive index of a sample can be accurately measured and this in turn can be
      used to identify a material, monitor contamination or dilution, etc. The sensor
      design we use here is based on a simple parallel-plate waveguide. A rectangular
      groove machined into one face acts as a resonant cavity (Figures 1 and 2). When
      terahertz radiation is coupled into the waveguide and propagates in the lowest
      order transverse-electric (TE1) mode, the result is a single strong resonant
      feature with a tunable resonant frequency that is dependent on the geometry of
      the groove. This groove can be filled with nonpolar liquid microfluidic samples
      which cause a shift in the observed resonant frequency that depends on the amount
      of liquid in the groove and its refractive index. Our technique has an advantage
      over other terahertz techniques in its simplicity, both in fabrication and
      implementation, since the procedure can be accomplished with standard laboratory
      equipment without the need for a clean room or any special fabrication or
      experimental techniques. It can also be easily expanded to multichannel operation
      by the incorporation of multiple grooves. In this video we will describe our
      complete experimental procedure, from the design of the sensor to the data
      analysis and determination of the sample refractive index.

PMID- 22951594
TI  - A genome-wide association study identifies a genetic variant in the SIAH2 locus
      associated with hormonal receptor-positive breast cancer in Japanese.
AB  - In Japan, breast cancer is the most common cancer among women and the second
      leading cause of cancer death among women worldwide. To identify genetic variants
      associated with the disease susceptibility, we performed a genome-wide
      association study (GWAS) using a total of 1086 Japanese female patients with
      hormonal receptor-positive (HRP) breast cancer and 1816 female controls. We
      selected 33 single-nucleotide polymorphisms (SNPs) with suggestive associations
      in GWAS (P-value of <1 * 10(-4)) as well as 4 SNPs that were previously
      implicated their association with breast cancer for further replication by an
      independent set of 1653 cases and 2797 controls. We identified significant
      association of the disease with a SNP rs6788895 (P(combined) of 9.43 * 10(-8)
      with odds ratio (OR) of 1.22) in the SIAH2 (intron of seven in absentia homolog
      2) gene on chromosome 3q25.1 where the involvement in estrogen-dependent diseases
      was suggested. In addition, rs3750817 in intron 2 of the fibroblast growth factor
      receptor 2 gene, which was reported to be associated with breast cancer
      susceptibility, was significantly replicated with P(combined) of 8.47 * 10(-8)
      with OR=1.22. Our results suggest a novel susceptibility locus on chromosome
      3q25.1 for a HRP breast cancer.

PMID- 22951595
TI  - Genome-wide association study identifies GYS2 as a novel genetic factor for
      polycystic ovary syndrome through obesity-related condition.
AB  - To investigate the role of genetic predisposition in the pathogenesis of
      polycystic ovary syndrome (PCOS) in relation to obesity, we performed a genome
      wide association study of PCOS in Koreans (n=1741). PCOS is a heterogeneous
      endocrinal disorder of uncertain etiology. Obesity is one of the well-known risk
      factors for PCOS. Genome-wide association study. Women with or without PCOS. A
      total of 1881 samples were genotyped using Illumina HumanOmni1 Quad v1 and
      processed by R packages. The PCOS patients were divided into two subgroups
      according to PCOS diagnostic criteria (Rotterdam and National Institutes of
      Health (NIH)). For PCOS-associated loci in the two definitions, we successfully
      confirmed significant associations of GYS2 for body mass index in the discovery
      stage. We further replicated pleiotropic associations of GYS2 in a childhood
      obesity study (n=482) and in a gestational diabetes study (n=1710), respectively.
      Our study provides a preliminary framework upon diverse genetic effects
      underlying PCOS in Korean women. A newly identified GYS2 gene as a predisposing
      factor of PCOS might expand understanding of the biological pathways in metabolic
      and endocrine regulation.

PMID- 22951596
TI  - Functional analysis of a lung cancer risk haplotype in the IL1B gene regulatory
      region.
AB  - Interleukin-1beta (IL-1beta), encoded by the IL1B gene, is a cytokine important
      in regulation of the inflammatory response. Elevated levels of IL1B expression
      have been associated with risk of gastric and lung cancer. We previously reported
      that a certain haplotype containing four single-nucleotide polymorphisms (SNPs) (
      3893G, -1464G, -511C and -31T; GGCT) in the IL1B gene regulatory region was
      associated with lung cancer risk and increased expression of the IL1B gene in the
      lung. In the present study, we have cloned the two haplotypes that were either
      protective (ACTC) or increasing lung cancer risk (GGCT) in a luciferase reporter
      vector system. We also cloned the IL1B -3893 and -1464 SNPs that were found to be
      associated with risk of lung cancer. The haplotype associated with lung cancer
      risk showed higher transcriptional activity in the human lung epithelial A549
      cell line in vitro. We also found that the IL1B -1464C allele increased
      transcriptional activity compared with the -1464G allele in the tumor necrosis
      factor alpha-stimulated cells, as well as specific transcription factor binding
      patterns to the IL1B -1464C allele. Interestingly, in vitro results showed a
      similar expression pattern as observed in the normal lung tissues of lung cancer
      patients reported earlier.

PMID- 22951597
TI  - Lateral tibial plateau fracture.
AB  - The patient was a 30-year-old man who was initially seen by a physical therapist
      for a chief complaint of left knee pain. Due to concern for a fracture, the
      physical therapist ordered radiographs of the left knee, which revealed a
      fracture of the left lateral tibial plateau. J Orthop Sports Phys Ther
      2012;42(9):819. doi:10.2519/jospt.2012.0416.

PMID- 22951598
TI  - Effect of physical exercise training on muscle strength and body composition, and
      their association with functional capacity and quality of life in patients with
      atrial fibrillation: a randomized controlled trial.
AB  - OBJECTIVE: Atrial fibrillation diminishes cardiac function, exercise tolerance
      and quality of life. The objective of this study was to determine whether
      exercise training in atrial fibrillation affects muscle strength, body
      composition, maximal exercise capacity and walking capacity positively, thus
      improving quality of life. DESIGN: Randomized clinical trial. Twelve weeks of
      physical exercise training or control. PATIENTS: Forty-nine patients in permanent
      atrial fibrillation were randomized to training or control. METHODS: Intervention
      consisted of aerobic training for 1 h 3 times per week at 70% of maximal exercise
      capacity vs control. Muscle strength, exercise capacity, 6-minute walk test, lean
      body mass, fat percentage, and quality of life were assessed. RESULTS: Muscle
      strength increased in the training group (p = 0.01), but no change was observed
      in controls. Lean body mass was unchanged in both groups. Fat percentage
      decreased in both groups, but there was no significant difference between the
      groups. Exercise capacity improved in the training group (p < 0.001), with no
      change in the control group. There was a significant difference after the
      training period between the training and control groups in terms of exercise
      capacity. (p = 0.001). Six-min walk test improved in the training group compared
      with controls (p < 0.01). Overall quality of life score, as measured by the
      Minnesota Living with Heart Failure Questionnaire, improved in the training group
      (p = 0.03). Quality of life, measured by Short Form-36, improved in the training
      group in 3 out of 8 subscales: physical functioning (p = 0.02), general health
      perceptions (p = 0.001) and vitality (p = 0.02). CONCLUSION: Muscle strength,
      exercise capacity and quality of life increased with exercise training in
      subjects with atrial fibrillation. Lean body mass was unchanged.

PMID- 22951599
TI  - High-throughput protein expression generator using a microfluidic platform.
AB  - Rapidly increasing fields, such as systems biology, require the development and
      implementation of new technologies, enabling high-throughput and high-fidelity
      measurements of large systems. Microfluidics promises to fulfill many of these
      requirements, such as performing high-throughput screening experiments on-chip,
      encompassing biochemical, biophysical, and cell-based assays. Since the early
      days of microfluidics devices, this field has drastically evolved, leading to the
      development of microfluidic large-scale integration. This technology allows for
      the integration of thousands of micromechanical valves on a single device with a
      postage-sized footprint (Figure 1). We have developed a high-throughput
      microfluidic platform for generating in vitro expression of protein arrays
      (Figure 2) named PING (Protein Interaction Network Generator). These arrays can
      serve as a template for many experiments such as protein-protein, protein-RNA or
      protein-DNA interactions. The device consist of thousands of reaction chambers,
      which are individually programmed using a microarrayer. Aligning of these printed
      microarrays to microfluidics devices programs each chamber with a single spot
      eliminating potential contamination or cross-reactivity. Moreover, generating
      microarrays using standard microarray spotting techniques is also very modular,
      allowing for the arraying of proteins, DNA, small molecules, and even colloidal
      suspensions. The potential impact of microfluidics on biological sciences is
      significant. A number of microfluidics based assays have already provided novel
      insights into the structure and function of biological systems, and the field of
      microfluidics will continue to impact biology.

PMID- 22951601
TI  - Antibiotics for surgical patients: the faster the better?

PMID- 22951600
TI  - Aggressive versus conservative initiation of antimicrobial treatment in
      critically ill surgical patients with suspected intensive-care-unit-acquired
      infection: a quasi-experimental, before and after observational cohort study.
AB  - BACKGROUND: Antimicrobial treatment in critically ill patients can either be
      started as soon as infection is suspected or after objective data confirm an
      infection. We postulated that delaying antimicrobial treatment of patients with
      suspected infections in the surgical intensive care unit (SICU) until objective
      evidence of infection had been obtained would not worsen patient mortality.
      METHODS: We did a 2-year, quasi-experimental, before and after observational
      cohort study of patients aged 18 years or older who were admitted to the SICU of
      the University of Virginia (Charlottesville, VA, USA). From Sept 1, 2008, to Aug
      31, 2009, aggressive treatment was used: patients suspected of having an
      infection on the basis of clinical grounds had blood cultures sent and
      antimicrobial treatment started. From Sept 1, 2009, to Aug 31, 2010, a
      conservative strategy was used, with antimicrobial treatment started only after
      objective findings confirmed an infection. Our primary outcome was in-hospital
      mortality. Analyses were by intention to treat. FINDINGS: Admissions to the SICU
      for the first and second years were 762 and 721, respectively, with 101 patients
      with SICU-acquired infections during the aggressive year and 100 patients during
      the conservative year. Compared with the aggressive approach, the conservative
      approach was associated with lower all-cause mortality (13/100 [13%] vs 27/101
      [27%]; p=0.015), more initially appropriate therapy (158/214 [74%] vs 144/231
      [62%]; p=0.0095), and a shorter mean duration of therapy (12.5 days [SD 10.7] vs
      17.7 [28.1]; p=0.0080). After adjusting for age, sex, trauma involvement, acute
      physiology and chronic health evaluation (APACHE) II score, and site of
      infection, the odds ratio for the risk of mortality in the aggressive therapy
      group compared with the conservative therapy group was 2.5 (95% CI 1.5-4.0).
      INTERPRETATION: Waiting for objective data to diagnose infection before treatment
      with antimicrobial drugs for suspected SICU-acquired infections does not worsen
      mortality and might be associated with better outcomes and use of antimicrobial
      drugs. FUNDING: National Institutes of Health.

PMID- 22951602
TI  - An excellent enzymatic lactic acid biosensor with ZnO nanowires-gated AlGaAs/GaAs
      high electron mobility transistor.
AB  - An excellent biosensor with ZnO nanowires-gated AlGaAs/GaAs high electron
      mobility transistor (HEMT) was used to detect lactic acid. Due to the new
      structure, addition of the Si-doped GaAs cap layer, the HEMT biosensor could
      detect a wide range of lactic acid concentrations from 0.03 nM to 300 mM. The
      novel biosensor exhibiting good performance along with fast response, high
      sensitivity, wide detection range, and long-term stability, can be integrated
      with a commercially available transmitter to realize lactic acid detection.

PMID- 22951603
TI  - Older adults with higher income or marriage have longer telomeres.
AB  - BACKGROUND: telomere length has been used to represent biological ageing and is
      found to be associated with various physiological, psychological and social
      factors. OBJECTIVE: to explore the effects of income and marriage on leucocyte
      telomere length in a representative sample of older adults. DESIGN AND SUBJECTS:
      cross-sectional analysis among 298 adults, aged 65-74, randomly selected from the
      community by census. METHODS: telomere length was measured by quantitative PCR.
      Participants provided information on sociodemographics, physical illness and
      completed questionnaires rating mental state and perceived neighbourhood
      experience. RESULTS: telomere length was negatively associated with lower income
      [coefficient -0.141 (95% CI: -0.244 to -0.020), P = 0.021] and positively
      associated with the marital status [coefficient 0.111 (95% CI: -0.008 to 0.234),
      P = 0.067] when controlling for gender, age, educational level, physical diseases
      (including diabetes, hypertension, cardiovascular diseases, cerebrovascular
      disease and Parkinson's disease), depressive symptoms, minor mental symptoms,
      cognitive impairment and perceived neighbourhood experience (including social
      support, perceived security and public facilities). CONCLUSIONS: these results
      indicate that older adults with higher income or being married have longer
      telomeres when other sociodemographics, physical diseases, mental status and
      neighbourhood experience are adjusted.

PMID- 22951604
TI  - Density-driven structural transformations in network forming glasses: a high
      pressure neutron diffraction study of GeO2 glass up to 17.5 GPa.
AB  - The structure of GeO(2) glass was investigated at pressures up to 17.5(5) GPa
      using in situ time-of-flight neutron diffraction with a Paris-Edinburgh press
      employing sintered diamond anvils. A new methodology and data correction
      procedure were developed, enabling a reliable measurement of structure factors
      that are largely free from diamond Bragg peaks. Calibration curves, which are
      important for neutron diffraction work on disordered materials, were constructed
      for pressure as a function of applied load for both single and double toroid
      anvil geometries. The diffraction data are compared to new molecular-dynamics
      simulations made using transferrable interaction potentials that include dipole
      polarization effects. The results, when taken together with those from other
      experimental methods, are consistent with four densification mechanisms. The
      first, at pressures up to approximately equal 5 GPa, is associated with a
      reorganization of GeO(4) units. The second, extending over the range from
      approximately equal 5 to 10 GPa, corresponds to a regime where GeO(4) units are
      replaced predominantly by GeO(5) units. In the third, as the pressure increases
      beyond ~10 GPa, appreciable concentrations of GeO(6) units begin to form and
      there is a decrease in the rate of change of the intermediate-range order as
      measured by the pressure dependence of the position of the first sharp
      diffraction peak. In the fourth, at about 30 GPa, the transformation to a
      predominantly octahedral glass is achieved and further densification proceeds via
      compression of the Ge-O bonds. The observed changes in the measured diffraction
      patterns for GeO(2) occur at similar dimensionless number densities to those
      found for SiO(2), indicating similar densification mechanisms for both glasses.
      This implies a regime from about 15 to 24 GPa where SiO(4) units are replaced
      predominantly by SiO(5) units, and a regime beyond ~24 GPa where appreciable
      concentrations of SiO(6) units begin to form.

PMID- 22951605
TI  - Multi-frequency EPR studies of a mononuclear holmium single-molecule magnet based
      on the polyoxometalate [Ho(III)(W5O18)2]9-.
AB  - Continuous-wave, multi-frequency electron paramagnetic resonance (EPR) studies
      are reported for a series of single-crystal and powder samples containing
      different dilutions of a recently discovered mononuclear Ho(III) (4f(10)) single
      molecule magnet (SMM) encapsulated in a highly symmetric polyoxometalate (POM)
      cage. The encapsulation offers the potential for applications in molecular
      spintronics devices, as it preserves the intrinsic properties of the nanomagnet
      outside of the crystal. A significant magnetic anisotropy arises due to a
      splitting of the Hund's coupled total angular momentum (J = L + S = 8) ground
      state in the POM ligand field. Thus, high-frequency (50.4 GHz) EPR studies reveal
      a highly anisotropic eight line spectrum corresponding to transitions within the
      lowest m(J) = +/-4 doublet, split by a strong hyperfine interaction with the I =
      7/2 Ho nucleus (100% natural abundance). X-band EPR studies reveal the presence
      of an appreciable tunneling gap between the m(J) = +/-4 doublet states having the
      same nuclear spin projection, leading to a highly non-linear field-dependence of
      the spectrum at low-frequencies.

PMID- 22951606
TI  - [The terminology, classifications and staging of neuroendocrine tumors of the
      pancreas].
AB  - The basic classifications, including the TNM and the WHO's classification of
      neuroendoctine tumors of the pancreas are highlighted. The WHO's dividing such
      tumors on G1 and G2 neuroendocrine lesions and G3 neuroendocrine carcinomas is
      substantiated.

PMID- 22951607
TI  - [The changes of intraabdominal pressure in patients with retroperitoneal
      bleeding].
AB  - The linear dependence of the intraabdominal pressure and the volume of
      retroperitoneal bleeding was revealed in 34 patients with the aortic aneurism
      rupture. In patients with the blunt abdominal trauma, treated conservatively and
      laparotomized (each group consisted of 26 patients), the intraabdominal pressure
      is higher in the operated group during the first day after the operation. The
      main factors of the intraabdominal hypertension seem to be shock and massive
      infusion and transfusion therapy.

PMID- 22951608
TI  - [The laparoscopic splenectomy in patients with hypersplenism, caused by liver
      cirrhosis].
AB  - The study aimed to assess the efficacy of the laparoscopic splenectomy in
      hematologic patients. The retrospective study included 147 patients with various
      hematologic diseases and hypersplenism operated during 2002-2010 yy. 125 (85.03%)
      conventional and 22 (14.97%) laparoscopic operations were carried out. The
      statistical difference were revealed only for the size and weight of the spleen
      and duration of the operation. The conventional group had 23.2% of complications
      and the laparoscopic group showed the 22.7% complication rate. The laparoscopic
      splenectomy was successfully carried in patients with the unchanged organ linear
      size (12.4 sm) and in younger patients. The choice of the surgical method was
      defined mainly by the spleen linear size.

PMID- 22951609
TI  - [The pancreaticogastroanastomosis by pancreatoduodenal resection].
AB  - The 10 year experience of pancreatoduodenal resection, consisting of 63
      operations was analyzed by the authors. The reconstructive stage of the operation
      included pancreaticojejunoanastomosis in 20 patients and
      pancreaticogastroanastomosis in the original modification in 43 patients. The
      method included the tamponization of the pancreatic stump with the mucosa layer
      of the gastric back wall. The suggested way of the pancreaticogastrostomy proved
      to shorten the operative time without increasing the postoperative morbidity and
      mortality rates.

PMID- 22951610
TI  - [The CT-guided transthoracic biopsy of lung's and mediastinal tumors].
AB  - The results of 107 CT-guided transthoracic biopsies, conducted during 2005-2010
      yy, were analyzed. The authors have shown the advantages of the core biopsy
      compared with the fine-needle aspiration biopsy (FNAB). Sensitivity of the first
      for the malignant tumors was 93%, while the FNAB sensitivity was only 75%. Though
      the core biopsy showed higher complication rates of the procedure. Both methods
      proved to be easy to use and should be used for the diagnostic purposes in cases
      of the peripheral lung tumors and mediastinal lymph nodes.

PMID- 22951611
TI  - [The primary tumour resection with extended D3 lymph node dissection, metastases
      of synchronous metastatic colorectal cancer].
AB  - The progress in colorectal cancer treatment of IV stage that was shown in last
      decades was mainly due to modern chemotherapy schemes and aggressive surgical
      approach towards distant metastatic lesions. Meanwhile less attention is paid to
      primary tumour treatment - the questions of necessity and volume of its resection
      are still open. The AIM of this study was to evaluate safety and oncologic
      effectiveness of primary tumour resection with D3 lymph node dissection in
      synchronous metastatic colorectal cancer. Patients with colorectal cancer and
      synchronous metastatic lesion of distant organs who underwent surgical resection
      of primary tumour were chosen from prospectively collected department database.
      The analysis of short-term and long-term results of resections with and without
      extended D3 lymph node dissection and prognostic factors affecting overall
      survival was carried out. From 2006 to 2011 total of 190 patients underwent
      primary tumour resection, 157 (82.6%) among them - with extended D3 lymph node
      dissection. Twenty one patient (11%) developed postoperative complications that
      required reintervention, 30-days mortality rate was 2.6%. Three-year cumulative
      overall survival was 37%, median survival - 22 months (25 months with extended
      lymph node dissection and 4 months without, p<0.001). Univariate analysis
      revealed following statistically significant prognostic factors improving overall
      survival: metastatic lesions in one distant organ, solitary haematogenous nodes,
      extended D3 lymph node dissection, postoperative chemotherapy, resection of
      metastatic lesions. Removal of primary tumour with extended lymph node dissection
      in metastatic colorectal cancer doesn't increase the number of postoperative
      complications and mortality. Performing D3 lymph node dissection favours increase
      of median survival and is a significant prognostic factor influencing outcomes.

PMID- 22951612
TI  - [The ethiology, pathogenesis, diagnostics and clinical features of the
      complicated posttraumatic rectal fistulae].
AB  - The ethiology, pathogenesis, diagnostics, clinical features and the capabilities
      of modern instrumental methods in the diagnosis of 134 patients with
      posttraumatic rectal fistulaes. The main causes of the rectal fistulae formation
      was the mechanism of the forecoming trauma, late hospital admission and
      postoperative complications. The use of modern diagnostic facilities allows to
      know the anatomic features of the fistulae, the presence of the septic cavities
      of the pararectal tissue, the involvement of sphincter muscles to the
      inflammatory process and their functional state. All the listed above facilitate
      the efficacy of the surgical treatment.

PMID- 22951613
TI  - [Correction of infringements of microcirculation at a widespread peritonitis].

PMID- 22951614
TI  - [The clinical and laboratory evaluation of the facial skin state after surgical
      correction].

PMID- 22951615
TI  - [The surgical treatment of giant malignant thymoma, invading pulmonary trunk,
      left lung and pericardium].

PMID- 22951616
TI  - [The autoimmune thyroiditis with subclinicsal thyreotoxicosis in the
      immunosupressed patient with renal transplant].

PMID- 22951617
TI  - [The surgical treatment of the combined hydatid disease].

PMID- 22951618
TI  - [The mesenteric-renal by-pass formation in patient with extrahepatic caval
      occlusion].

PMID- 22951619
TI  - [The esophagus extirpation with the extended right hemihepatectomy as the
      surgical treatment of the giant GIST-tumor].

PMID- 22951620
TI  - [The primary bone plasty of the mandibular with the use of autotransplant and the
      Collost membrane].

PMID- 22951621
TI  - Endothelium and hemorheology.
AB  - A number of factors are involved in the regulation and maintenance of vascular
      homeostasis. The role of the vascular endothelium has been identified almost
      three decades ago, and a number of lines of evidence provide solid support to the
      role of this tissue in modulating not only vascular tone, but also phenomena such
      as platelet, red blood cell aggregation and deformability. In turn,
      hemorheological characteristics have been proven to impact on the endothelial
      release of mediators and therefore on vascular tone. Both biochemical and
      physical stimuli are sensed by the endothelium as stimuli for the release of
      oxygen free radicals and nitric oxide. In particular, changes in blood viscosity
      have a direct effect on shear stress, which is believed to be the physiological
      stimulus for endothelial activation. These considerations have lead us to
      formulate an alternative hypothesis for the meaning of hyperviscosity in the
      setting of ischemic syndromes. While this hypothesis is supported by animal data,
      the evidence of cross-sectional human studies is controversial. This evidence is
      discussed in the present review.

PMID- 22951622
TI  - Comparative hemorheology.
AB  - Comparative data on blood composition and blood flow properties indicate
      different levels of interspecies variation for several parameters. Hematocrit and
      hemoglobin levels have relatively low variability among mammals, while mean cell
      volume and red blood cell (RBC) count are more variable. There is also a
      difference of variability between high and low shear rate blood viscosity in
      mammals, with low shear rate viscosity having a higher degree of interspecies
      variation. This observation parallels the diversity of RBC aggregation among
      mammalian species. Allometric relations for blood rheology parameters indicate
      highly significant correlations of low shear rate blood viscosity and RBC
      aggregation with body weight, especially if species belonging to the order
      Artiodactyla are excluded. These allometric relations can be used to formulate
      various hypotheses about the evolutionary histories of circulatory functions, as
      well as hypotheses related to the role of RBC aggregation in the mammalian
      circulatory system. Such comparative studies and analytical reasoning based on
      comparative data may contribute to answering the "why" questions, and accordingly
      may improve our understanding of circulatory functions and hence may have
      possible clinical importance. During the last several decades, similar approaches
      to various medical concepts have yielded a new approach to medicine that is now
      known as Evolutionary Medicine.

PMID- 22951623
TI  - Pathophysiology of the contrast media-induced nephropathy (CIN) in patients
      undergoing coronary interventions.
AB  - Contrast media-induced nephropathy (CIN) is a known complication of intra
      arterial application of radiographic contrast media (RCM) and is associated with
      both short- and long-term outcomes. The development of CIN is not easy to
      diagnose due to a lack of a uniform definition of CIN. CIN was reported in 4 to
      20% of patients after intra-arterial RCM administration during coronary
      angiography. An all-cause mortality rate of CIN patients amounted to 9% compared
      with 2% among patients not developing CIN. Pre-existing chronic renal
      insufficiency, especially, was described as important factor predisposing for
      CIN, but there was recent clinical evidence that CIN may occur also in low risk
      ambulatory patients, probably depending on the type of RCM used. Strongly
      depending on the type of RCM administered there were marked differences in the
      morphological changes of erythrocytes as well as endothelial cells coinciding in
      some cases with microcirculatory disorders in patients as well as in animal
      models. Iodixanol brought about the least cellular and microcirculatory effects
      while Iopromide induced the strongest disturbances in capillary perfusion and
      myocardial oxygen tension. It is unclear, however, whether this favours the
      development of CIN.

PMID- 22951624
TI  - Role molecular signaling pathways in changes of red blood cell deformability.
AB  - This study was designed to investigate the dependency of the red blood cell
      deformability upon activation of extra- and intracellular signaling pathways.
      Exposures of red blood cells (RBCs) to catecholamines and to insulin led to
      positive change in the RBC deformability. When forskolin, a stimulator of
      adenylyl cyclase (AC), was added to RBC suspension, the RBC deformability was
      increased. Somewhat more significant deformability rise appeared after RBC
      incubation with dB-AMP. The inhibitors of phosphodiesterase (PDE) activity
      increased red cell deformability. These results revealed a considerable role of
      the AC-cAMP signaling system in the regulation of red blood cell deformability.
      The rise of the red blood cell Ca(2+) influx, stimulated by mechanical loading or
      A23187 was accompanied by a marked lowering of RBC deformability. At the same
      time blocking of Ca(2+) entry into RBC by verapamil or Ca(2+) chelating by EGTA
      led to significant deformability rise. The comparison of the effect of the
      different protein kinases on the red blood cell deformability showed that it was
      altered more considerable under PKA activation by forskolin or dB-cAMP than by
      other protein kinases. There was a lesser but quite statistically significant
      effect of tyrosine protein kinase (TPK) on RBC microrheology. Whereas the
      microrheological effect of PKC was not so considerable. The problem of the short
      term regulation of red blood cell microrheology is examined. The latter includes:
      the modes of activation of extra- and intracellular molecular signaling pathways,
      ligand - receptor interaction, second messengers, membrane protein
      phosphorylation. On the whole the total data clearly show that the red cell
      deformability changes are connected with activation of different extra - and
      intracellular signaling pathways. It seems reasonable to suppose that red blood
      cell deformability changes were mainly associated with activation of the AC-cAMP
      PKA pathway, and with decrease of Ca(2+) entry into cells.

PMID- 22951625
TI  - Aerobic training-induced improvements in arterial stiffness are not sustained in
      older adults with multiple cardiovascular risk factors.
AB  - There is a well-established relationship between increased arterial stiffness and
      cardiovascular mortality. We examined whether a long-term aerobic exercise
      intervention (6 months) would increase arterial compliance in older adults with
      hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of
      52 older adults (mean age 69.3+/-0.6 years, 30 males and 22 females) with
      diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia
      were recruited. Subjects were randomly assigned to one of two groups: an aerobic
      group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6
      months of no aerobic exercise, NA group). Arterial stiffness was measured as
      pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased
      arterial stiffness as measured by both radial (P=0.001, 2-way analysis of
      variance with repeated measures) and femoral (P=0.002) PWV. This was due to a
      decrease in arterial stiffness in the AT group after 3 months of training, which
      was not maintained after 6-month training for either radial (P=0.707) or femoral
      (P=0.680) PWV. Our findings indicate that in older adults with multiple
      cardiovascular risk factors, short-term improvements in arterial stiffness became
      attenuated over the long term.

PMID- 22951626
TI  - Extinction training during the reconsolidation window prevents recovery of fear.
AB  - Fear is maladaptive when it persists long after circumstances have become safe.
      It is therefore crucial to develop an approach that persistently prevents the
      return of fear. Pavlovian fear-conditioning paradigms are commonly employed to
      create a controlled, novel fear association in the laboratory. After pairing an
      innocuous stimulus (conditioned stimulus, CS) with an aversive outcome
      (unconditioned stimulus, US) we can elicit a fear response (conditioned response,
      or CR) by presenting just the stimulus alone. Once fear is acquired, it can be
      diminished using extinction training, whereby the conditioned stimulus is
      repeatedly presented without the aversive outcome until fear is no longer
      expressed. This inhibitory learning creates a new, safe representation for the
      CS, which competes for expression with the original fear memory. Although
      extinction is effective at inhibiting fear, it is not permanent. Fear can
      spontaneously recover with the passage of time. Exposure to stress or returning
      to the context of initial learning can also cause fear to resurface. Our protocol
      addresses the transient nature of extinction by targeting the reconsolidation
      window to modify emotional memory in a more permanent manner. Ample evidence
      suggests that reactivating a consolidated memory returns it to a labile state,
      during which the memory is again susceptible to interference. This window of
      opportunity appears to open shortly after reactivation and close approximately 6
      hrs later, although this may vary depending on the strength and age of the
      memory. By allowing new information to incorporate into the original memory
      trace, this memory may be updated as it reconsolidates. Studies involving non
      human animals have successfully blocked the expression of fear memory by
      introducing pharmacological manipulations within the reconsolidation window,
      however, most agents used are either toxic to humans or show equivocal effects
      when used in human studies. Our protocol addresses these challenges by offering
      an effective, yet non-invasive, behavioral manipulation that is safe for humans.
      By prompting fear memory retrieval prior to extinction, we essentially trigger
      the reconsolidation process, allowing new safety information (i.e., extinction)
      to be incorporated while the fear memory is still susceptible to interference. A
      recent study employing this behavioral manipulation in rats has successfully
      blocked fear memory using these temporal parameters. Additional studies in humans
      have demonstrated that introducing new information after the retrieval of
      previously consolidated motor, episodic, or declarative memories leads to
      interference with the original memory trace. We outline below a novel protocol
      used to block fear recovery in humans.

PMID- 22951627
TI  - Fast pH-assisted functionalization of silver nanoparticles with monothiolated
      DNA.
AB  - Attaching monothiolated DNA to silver nanoparticles has been achieved at pH 3.0
      in 30 minutes and difficulties associated with DNA attachment to AgNPs at neutral
      pH have been revealed by studying DNA adsorption kinetics.

PMID- 22951628
TI  - The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting:
      a systematic review.
AB  - BACKGROUND: Ginger has been used throughout the world as a therapeutic agent for
      centuries. The herb is increasingly used in Western society also, with one of the
      most common indications being pregnancy-induced nausea and vomiting (PNV).
      OBJECTIVES: To examine the evidence for the safety and effectiveness of ginger
      for PNV. METHODS: Randomised controlled trials (RCTs) of ginger and PNV were
      sourced from CINAHL, the Cochrane library, MEDLINE and TRIP. The methodological
      quality of RCTs was assessed using the Critical Appraisal Skills Programme (CASP)
      tool. RESULTS: Four RCTs met the inclusion criteria. All trials found orally
      administered ginger to be significantly more effective than placebo in reducing
      the frequency of vomiting and intensity of nausea. Adverse events were generally
      mild and infrequent. CONCLUSION: The best available evidence suggests that ginger
      is a safe and effective treatment for PNV. However, there remains uncertainty
      regarding the maximum safe dosage of ginger, appropriate duration of treatment,
      consequences of over-dosage, and potential drug-herb interactions; all of which
      are important areas for future research.

PMID- 22951629
TI  - Features of twins and stacking faults in silver nanorice and electron-beam
      irradiation effect.
AB  - Systematic structural characterization using high resolution transmission
      electron microscope (HRTEM), selected area electron diffraction (SAED) and
      diffractogram analysis of silver nanorice was aimed to reveal the characteristic
      features of twins and stacking faults, faceting effect and smoothing phenomena of
      outer surfaces. Nucleation, growth and crystallization of new nanocrystals, and
      depletion of parent nanorice was observed by the in situ TEM through electron
      beam irradiation. It can be seen that the fundamental growth mechanism of the new
      nucleus is Ag atom diffusion or migration through carbon film supported these
      crystals. Twins in the as-grown nanorice is a reflection twin with {111} lattice
      plane as the common plane, and they are formed by 120 degrees  or 60 degrees 
      rotation about the reference twin lamella. Shockley partial dislocation was
      formed by the {111} lattice plane shifting along the <112> direction with the
      Burgers vector a/6 <112>. Twin faults occur in the form of adjacent twin lamellas
      inserted into a single atomic plane. Growth morphology analysis suggests that
      {111} and {001} lattice planes with the minimum surface attachment energy have a
      tendency to facet.

PMID- 22951630
TI  - Tenofovir use and pregnancy among women initiating HAART.
AB  - OBJECTIVE: Recent studies have raised concerns about a change in rates of
      pregnancy among HIV-negative women exposed to tenofovir. Here, our objective was
      to determine among HIV-positive women whether use of tenofovir at HAART
      initiation or thereafter is associated with subsequent changes in incidence of
      pregnancy. DESIGN: Analysis of prospectively collected clinical data. METHODS: We
      used Cox proportional hazards models and logistic regression to estimate hazard
      ratios and odds ratios for the association of baseline tenofovir use and first
      incident pregnancy. We used marginal structural Cox models to estimate hazard
      ratios for the association of current tenofovir use and time to first incident
      pregnancy. RESULTS: We studied 7275 women, of whom 1199 were initiated on
      tenofovir-based HAART regimens, and who experienced a total of 894 pregnancies in
      17,200 person-years of follow-up. Analyses showed slight reductions in hazards of
      pregnancy among women who used tenofovir but without sufficient precision to draw
      strong conclusions. Sensitivity analyses confirmed main results. CONCLUSIONS:
      Tenofovir may be associated with a lower hazard or rate of pregnancy in women
      receiving HAART. However, conclusions are limited by low precision, the
      observational nature of the data, and possible uncontrolled confounding by
      temporal trends in contraception use and other factors.

PMID- 22951631
TI  - Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons.
AB  - OBJECTIVE: The incidence of certain non-AIDS-defining cancers (NADCs) in HIV
      patients has been reported to have increased in the combination antiretroviral
      therapy (ART) era. Studies are needed to directly evaluate the effect of ART use
      on cancer risk. DESIGN: We followed 12 872 HIV-infected Kaiser Permanente members
      whose complete ART history was known for incident cancers between 1996 and 2008.
      METHODS: Cancers, identified from Surveillance, Epidemiology, and End Results
      (SEER)-based cancer registries, were grouped as ADCs, infection-related NADCs, or
      infection-unrelated NADCs. We also evaluated the most common individual cancer
      types. Rate ratios for ART use (yes/no) and cumulative duration of any ART,
      protease inhibitor, and nonnucleotide reverse transcriptase inhibitor (NNRTI)
      therapy were obtained from Poisson models adjusting for demographics,
      pretreatment or recent CD4 cell count and HIV RNA levels, years known HIV
      infected, prior antiretroviral use, HIV risk, smoking, alcohol/drug abuse,
      overweight/obesity, and calendar year. RESULTS: The cohort experienced 32 368
      person-years of ART, 21 249 person-years of protease inhibitor therapy, and 15
      643 person-years of NNRTI therapy. The mean follow-up duration was 4.5 years. ADC
      rates decrease with increased duration of ART use [rate ratio per year = 0.61
      (95% confidence interval 0.56-0.66)]; the effect was similar by therapy class.
      ART, protease inhibitor, or NNRTI therapy duration was not associated with
      infection-related or infection-unrelated NADC [rate ratio per year ART = 1.00
      (0.91-1.11) and 0.96 (0.90-1.01), respectively], except a higher anal cancer risk
      with longer protease inhibitor therapy [rate ratio per year = 1.16 (1.02-1.31)].
      CONCLUSION: No therapy class-specific effect was found for ADC. ART exposure was
      generally not associated with NADC risk, except for long-term use of protease
      inhibitor, which might be associated with increased anal cancer risk.

PMID- 22951632
TI  - Underlying genetic structure impacts the association between CYP2B6 polymorphisms
      and response to efavirenz and nevirapine.
AB  - OBJECTIVE: CYP2B6 variation predicts pharmacokinetic characteristics of its
      substrates. Consideration for underlying genetic structure is critical to protect
      against spurious associations with the highly polymorphic CYP2B6 gene. DESIGN:
      The effect of CYP2B6 variation on response to its substrates, nonnucleoside
      reverse transcriptase inhibitors (NNRTIs), was explored in the Women's
      Interagency HIV Study. METHODS: Five putative functional polymorphisms were
      tested for associations with virologic suppression within 1 year after NNRTI
      initiation in women naive to antiretroviral agents (n = 91). Principal components
      were generated to control for population substructure. Logistic regression was
      used to test the joint effect of rs3745274 and rs28399499, which together
      indicate slow, intermediate, and extensive metabolizers. RESULTS: Rs3745274 was
      significantly associated with virologic suppression [odds ratio = 3.61, 95%
      confidence interval (CI) 1.16-11.22, P trend = 0.03]; the remaining polymorphisms
      tested were not significantly associated with response. Women classified as
      intermediate and slow metabolizers were 2.90 (95% CI 0.79-12.28) and 13.44 (95%
      CI 1.66 to infinity) times as likely to achieve virologic suppression compared to
      extensive metabolizers after adjustment for principal components (P trend =
      0.005). Failure to control for genetic ancestry resulted in substantial
      confounding of the relationship between the metabolizer phenotype and treatment
      response. CONCLUSION: The CYP2B6 metabolizer phenotype was significantly
      associated with virologic response to NNRTIs; this relationship would have been
      masked by simple adjustment for self-reported ethnicity. Given the appreciable
      genetic heterogeneity that exists within self-reported ethnicity, these results
      exemplify the importance of characterizing underlying genetic structure in
      pharmacogenetic studies. Further follow-up of the CYP2B6 metabolizer phenotype is
      warranted, given the potential clinical importance of this finding.

PMID- 22951633
TI  - The impact of HIV and ART on recurrent tuberculosis in a sub-Saharan setting.
AB  - OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on the
      incidence of recurrent tuberculosis (TB) in an African population. DESIGN: A long
      term population cohort in Karonga District, northern Malawi. METHODS: Patients
      who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were
      visited annually to record vital status, ART use and screen for TB. Survival
      analysis estimated the effect of HIV/ART status at completion of treatment on
      mortality and recurrence. Analyses were stratified by time since treatment
      completion to estimate the effects on relapse (predominates during first year)
      and reinfection disease (predominates later). RESULTS: Among 1133 index TB cases
      contributing 4353 person-years of follow-up, there were 307 deaths and 103
      laboratory-confirmed recurrences (recurrence rate 4.6 per 100 person-years). Half
      the recurrences occurred in the first year since completing treatment. HIV
      infection increased the recurrence rate [rate ratio adjusted for age, sex, period
      and TB type 2.69, 95% confidence interval (CI) 1.69-4.26], but with less effect
      in the first year (adjusted rate ratio 1.71, 95% CI 0.87-3.35) than subsequently
      (adjusted rate ratio 4.2, 95% CI 2.16-8.15). Recurrence rates on ART were
      intermediate between those of HIV-negative individuals and HIV-positive
      individuals without ART. Compared with HIV-positive individuals without ART, the
      adjusted rate ratio was 0.74 (95% CI 0.27-2.06) in the first year, and 0.43 (95%
      CI 0.11-1.73) later. CONCLUSION: The increased incidence of TB recurrence
      observed in HIV-positive patients appeared to be reduced by ART. The effects are
      mostly on later (likely reinfection) disease so the impact of ART on reducing
      recurrence will be highest in high TB incidence settings.

PMID- 22951634
TI  - Adherence to antiretroviral therapy during and after pregnancy in low-income,
      middle-income, and high-income countries:  a systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate antiretroviral therapy (ART) adherence rates during
      pregnancy and postpartum in high-income, middle-income, and low-income countries.
      DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, SCI Web of
      Science, NLM Gateway, and Google scholar databases were searched. We included all
      studies reporting adherence rates as a primary or secondary outcome among HIV
      infected pregnant women. Two independent reviewers extracted data on adherence
      and study characteristics. A random-effects model was used to pool adherence
      rates; sensitivity, heterogeneity, and publication bias were assessed. RESULTS:
      Of 72 eligible articles, 51 studies involving 20 153 HIV-infected pregnant women
      were included. Most studies were from United States (n =  14, 27%) followed by
      Kenya (n = 6, 12%), South Africa (n = 5, 10%), and Zambia (n = 5, 10%). The
      threshold defining good adherence to ART varied across studies (>80, >90, >95,
      100%). A pooled analysis of all studies indicated a pooled estimate of 73.5% [95%
      confidence interval (CI) 69.3-77.5%] of pregnant women who had adequate (>80%)
      ART adherence. The pooled proportion of women with adequate adherence levels was
      higher during the antepartum (75.7%, 95% CI 71.5-79.7%) than during postpartum
      (53.0%, 95% CI 32.8-72.7%; P = 0.005). Selected reported barriers for
      nonadherence included physical, economic and emotional stresses, depression
      (especially postdelivery), alcohol or drug use, and ART dosing frequency or pill
      burden. CONCLUSION: Our findings indicate that only 73.5% of pregnant women
      achieved optimal ART adherence. Reaching adequate ART adherence levels was a
      challenge in pregnancy, but especially during the postpartum period. Further
      research to investigate specific barriers and interventions to address them is
      urgently needed globally.

PMID- 22951635
TI  - Fractures after antiretroviral initiation.
AB  - BACKGROUND: Bone mineral density declines by 2-6% within 1-2 years after
      initiation of antiretroviral therapy (ART); however, it is uncertain whether this
      results in an immediate or cumulative increase in fracture rates. METHODS: We
      evaluated the incidence and predictors of fracture in 4640 HIV-positive
      participants from 26 randomized ART studies followed in the AIDS Clinical Trials
      Group (ACTG) Longitudinal-Linked Randomized Trial study for a median of 5 years.
      Fragility and nonfragility fractures were recorded prospectively at semiannual
      visits. Incidence was calculated as fractures/total person-years. Cox
      proportional hazards models evaluated effects of traditional fracture risks, HIV
      disease characteristics, and ART exposure on fracture incidence. RESULTS: Median
      (interquartile range) age was 39 (33, 45) years; 83% were men, 48% white, and
      median nadir CD4 cell count was 187 (65, 308) cells/MUl. Overall, 116 fractures
      were reported in 106 participants with median time-to-first fracture of 2.3
      years. Fracture incidence was 0.40 of 100 person-years among all participants and
      0.38 of 100 person-years among 3398 participants who were ART naive at enrollment
      into ACTG parent studies. Among ART-naive participants, fracture rates were
      higher within the first 2 years after ART initiation (0.53/100 person-years) than
      subsequent years (0.30/100 person-years). In a multivariate analysis of ART-naive
      participants, increased hazard of fracture was associated with current smoking
      and glucocorticoid use but not with exposure to specific antiretrovirals.
      CONCLUSION: Fracture rates were higher within the first 2 years after ART
      initiation, relative to subsequent years. However, continuation of ART was not
      associated with increasing fracture rates in these relatively young HIV-positive
      individuals.

PMID- 22951636
TI  - HIV infection and glycemic response to newly initiated diabetic medical therapy.
AB  - OBJECTIVES: Type 2 diabetes (DM2) is increasingly common in HIV-infected
      individuals. Antiretroviral agents and chronic inflammation may adversely affect
      glycemic control. However, little is known about the effectiveness of diabetic
      medical therapy in HIV-infected patients. The objective of this study was to
      compare the effectiveness of initial diabetic medical therapy in patients with
      and without HIV infection. DESIGN: A retrospective cohort study was conducted
      among adults with DM2 initiating diabetic medications within the Centers for AIDS
      Research Network of Integrated Clinical Systems cohort. METHODS: Generalized
      estimating equations were used to compare changes in hemoglobin A1c (HbA1c)
      through the year after initiation of therapy, controlling for baseline HbA1c and
      demographic and clinical covariates. RESULTS: Two hundred and eighty-six HIV
      infected patients and 858 age and sex-matched HIV-uninfected patients initiated
      diabetic medications during the study period. Overall, patients had an adjusted
      absolute mean reduction in HbA1c of 1.04% [95% confidence interval (CI) -0.87 to 
      1.22] during the first year of therapy. HIV-infected patients achieved
      significantly smaller reductions in HbA1c, with an absolute mean difference of 
      0.17% (95% CI -0.28 to -0.06; P = 0.003). On subanalyses, HIV-infected patients
      on a protease inhibitor-based regimen had significantly smaller reductions in
      HbA1c compared to HIV-uninfected patients (adjusted absolute difference -0.21%,
      95% CI -0.35 to -0.08; P = 0.002). CONCLUSION: Patients with HIV infection who
      initiate diabetic medical therapy achieve smaller reductions in HbA1c than
      patients without HIV infection in the course of routine clinical care. This less
      robust response may in part be related to use of antiretrovirals that exacerbate
      insulin resistance, specifically protease inhibitors.

PMID- 22951637
TI  - Spatial accessibility and the spread of HIV-1 subtypes and recombinants.
AB  - OBJECTIVE/DESIGN: The global spread of HIV-1 main group (group M) has resulted in
      differential distributions of subtypes and recombinants, with the greatest
      diversity being found in sub-Saharan Africa. The explanations for the current
      subtype distribution patterns are likely multifactorial, but the promotion of
      human migrations and movements through transportation link availability and
      quality, summarized through 'accessibility', have been consistently cited as
      strong drivers. We sought to address the question of whether accessibility has
      been a significant factor in HIV-1 spread across mainland Africa through spatial
      analyses of molecular epidemiology, transport network and land cover data.
      METHODS: The distribution of HIV-1 subtypes and recombinants in sub-Saharan
      Africa for the period 1998-2008 was mapped using molecular epidemiology data at a
      finer level of detail than ever before. Moreover, hypotheses on the role of
      distance, road network structure and accessibility in explaining the patterns
      seen were tested using spatial datasets representing African transport
      infrastructure, land cover and an accessibility model of landscape travel speed.
      RESULTS: Coherent spatial patterns in HIV-1 subtype distributions across the
      continent exist, and a substantial proportion of the variance in the distribution
      and diversity pattern seen can be explained by variations in regional spatial
      accessibility. CONCLUSION: The study confirms quantitatively the influence of
      transport infrastructure on HIV-1 spread within Africa, presents an approach for
      examining potential future impacts of road development projects and, more
      generally, highlights the importance of accessibility in the spread of
      communicable diseases.

PMID- 22951639
TI  - Gde2 regulates cortical neuronal identity by controlling the timing of cortical
      progenitor differentiation.
AB  - The mammalian cortex is a multilaminar structure consisting of specialized layer
      specific neurons that form complex circuits throughout the brain and spinal cord.
      These neurons are generated in a defined sequence dictated by their birthdate
      such that early-born neurons settle in deep cortical layers whereas late-born
      neurons populate more superficial layers. Cortical neuronal birthdate is partly
      controlled by an intrinsic clock-type mechanism; however, the role of extrinsic
      factors in the temporal control of cell-cycle exit is less clear. Here, we show
      that Gde2, a six-transmembrane protein that induces spinal neuronal
      differentiation, is expressed in the developing cortex throughout cortical
      neurogenesis. In the absence of Gde2, cortical progenitors fail to exit the cell
      cycle on time, remain cycling, accumulate and exit the cell cycle en masse
      towards the end of the neurogenic period. These dynamic changes in cell-cycle
      progression cause deficits and delays in deep-layer neuronal differentiation and
      robust increases in superficial neuronal numbers. Gde2(-/-) cortices show
      elevated levels of Notch signaling coincident with when progenitors fail to
      differentiate, suggesting that abnormal Notch activation retains cells in a
      proliferative phase that biases them to superficial fates. However, no change in
      Notch signaling is observed at the time of increased cell-cycle exit. These
      observations define a key role for Gde2 in controlling cortical neuronal fates by
      regulating the timing of neurogenesis, and show that loss of Gde2 uncovers
      additional mechanisms that trigger remaining neuronal progenitors to
      differentiate at the end of the neurogenic period.

PMID- 22951640
TI  - Zebrafish rest regulates developmental gene expression but not neurogenesis.
AB  - The transcriptional repressor Rest (Nrsf) recruits chromatin-modifying complexes
      to RE1 'silencer elements', which are associated with hundreds of neural genes.
      However, the requirement for Rest-mediated transcriptional regulation of
      embryonic development and cell fate is poorly understood. Conflicting views of
      the role of Rest in controlling cell fate have emerged from recent studies. To
      address these controversies, we examined the developmental requirement for Rest
      in zebrafish using zinc-finger nuclease-mediated gene targeting. We discovered
      that germ layer specification progresses normally in rest mutants despite
      derepression of target genes during embryogenesis. This analysis provides the
      first evidence that maternal rest is essential for repression of target genes
      during blastula stages. Surprisingly, neurogenesis proceeds largely normally in
      rest mutants, although abnormalities are observed within the nervous system,
      including defects in oligodendrocyte precursor cell development and a partial
      loss of facial branchiomotor neuron migration. Mutants progress normally through
      embryogenesis but many die as larvae (after 12 days). However, some homozygotes
      reach adulthood and are viable. We utilized an RE1/NRSE transgenic reporter
      system to dynamically monitor Rest activity. This analysis revealed that Rest is
      required to repress gene expression in mesodermal derivatives including muscle
      and notochord, as well as within the nervous system. Finally, we demonstrated
      that Rest is required for long-term repression of target genes in non-neural
      tissues in adult zebrafish. Our results point to a broad role for Rest in fine
      tuning neural gene expression, rather than as a widespread regulator of
      neurogenesis or cell fate.

PMID- 22951641
TI  - The histone acetyltransferases CBP and Chameau integrate developmental and DNA
      replication programs in Drosophila ovarian follicle cells.
AB  - DNA replication origin activity changes during development. Chromatin
      modifications are known to influence the genomic location of origins and the time
      during S phase that they initiate replication in different cells. However, how
      chromatin regulates origins in concert with cell differentiation remains poorly
      understood. Here, we use developmental gene amplification in Drosophila ovarian
      follicle cells as a model to investigate how chromatin modifiers regulate origins
      in a developmental context. We find that the histone acetyltransferase (HAT)
      Chameau (Chm) binds to amplicon origins and is partially required for their
      function. Depletion of Chm had relatively mild effects on origins during gene
      amplification and genomic replication compared with previous knockdown of its
      ortholog HBO1 in human cells, which has severe effects on origin function. We
      show that another HAT, CBP (Nejire), also binds amplicon origins and is partially
      required for amplification. Knockdown of Chm and CBP together had a more severe
      effect on nucleosome acetylation and amplicon origin activity than knockdown of
      either HAT alone, suggesting that these HATs collaborate in origin regulation. In
      addition to their local function at the origin, we show that Chm and CBP also
      globally regulate the developmental transition of follicle cells into the
      amplification stages of oogenesis. Our results reveal a complexity of origin
      epigenetic regulation by multiple HATs during development and suggest that
      chromatin modifiers are a nexus that integrates differentiation and DNA
      replication programs.

PMID- 22951642
TI  - Multifaceted roles of PTEN and TSC orchestrate growth and differentiation of
      Drosophila blood progenitors.
AB  - The innate plasticity of hematopoietic progenitors is tightly regulated to supply
      blood cells during normal hematopoiesis and in response to stress or infection.
      We demonstrate that in the Drosophila lymph gland (LG) the tumor suppressors TSC
      and PTEN control blood progenitor proliferation through a common TOR- and 4EBP
      dependent pathway. Tsc2 or Pten deficiency in progenitors increases TOR signaling
      and causes LG overgrowth by increasing the number of actively dividing cells that
      accumulate high levels of phosphorylated (p) 4EBP during a critical window of
      growth. These phenotypes are associated with increased reactive oxygen species
      (ROS) levels in the LG, and scavenging ROS in progenitors is sufficient to rescue
      overgrowth. Blood progenitor number is also sensitive to starvation and hypoxia
      in a TOR-dependent manner. Differences between Tsc1/2 and Pten function become
      apparent at later stages. Loss of Tsc1/2 autonomously increases p4EBP and
      decreases pAKT levels, expands the number of intermediate progenitors and limits
      terminal differentiation, except for a late induction of lamellocytes. By
      contrast, absence of PTEN increases p4EBP and pAKT levels and induces
      myeloproliferative expansion of plasmatocytes and crystal cells. This increased
      malignancy is associated with non-autonomous increases in p4EBP levels within
      peripheral differentiating hemocytes, culminating in their premature release into
      circulation and demonstrating potential non-autonomous effects of Pten
      dysfunction on malignancy. This study highlights mechanistic differences between
      TSC and PTEN on TOR function and demonstrates the multifaceted roles of a
      nutrient-sensing pathway in orchestrating proliferation and differentiation of
      myeloid-specific blood progenitors through regulation of ROS levels and the
      resulting myeloproliferative disorder when dysregulated.

PMID- 22951643
TI  - Muscle length and myonuclear position are independently regulated by distinct
      Dynein pathways.
AB  - Various muscle diseases present with aberrant muscle cell morphologies
      characterized by smaller myofibers with mispositioned nuclei. The mechanisms that
      normally control these processes, whether they are linked, and their contribution
      to muscle weakness in disease, are not known. We examined the role of Dynein and
      Dynein-interacting proteins during Drosophila muscle development and found that
      several factors, including Dynein heavy chain, Dynein light chain and Partner of
      inscuteable, contribute to the regulation of both muscle length and myonuclear
      positioning. However, Lis1 contributes only to Dynein-dependent muscle length
      determination, whereas CLIP-190 and Glued contribute only to Dynein-dependent
      myonuclear positioning. Mechanistically, microtubule density at muscle poles is
      decreased in CLIP-190 mutants, suggesting that microtubule-cortex interactions
      facilitate myonuclear positioning. In Lis1 mutants, Dynein hyperaccumulates at
      the muscle poles with a sharper localization pattern, suggesting that retrograde
      trafficking contributes to muscle length. Both Lis1 and CLIP-190 act downstream
      of Dynein accumulation at the cortex, suggesting that they specify Dynein
      function within a single location. Finally, defects in muscle length or
      myonuclear positioning correlate with impaired muscle function in vivo,
      suggesting that both processes are essential for muscle function.

PMID- 22951644
TI  - S1P1 inhibits sprouting angiogenesis during vascular development.
AB  - Coordination between the vascular system and forming organs is essential for
      proper embryonic development. The vasculature expands by sprouting angiogenesis,
      during which tip cells form filopodia that incorporate into capillary loops.
      Although several molecules, such as vascular endothelial growth factor A (Vegfa),
      are known to induce sprouting, the mechanism that terminates this process to
      ensure neovessel stability is still unknown. Sphingosine-1-phosphate receptor 1
      (S1P(1)) has been shown to mediate interaction between endothelial and mural
      cells during vascular maturation. In vitro studies have identified S1P(1) as a
      pro-angiogenic factor. Here, we show that S1P(1) acts as an endothelial cell (EC)
      autonomous negative regulator of sprouting angiogenesis during vascular
      development. Severe aberrations in vessel size and excessive sprouting found in
      limbs of S1P(1)-null mouse embryos before vessel maturation imply a previously
      unknown, mural cell-independent role for S1P(1) as an anti-angiogenic factor. A
      similar phenotype observed when S1P(1) expression was blocked specifically in ECs
      indicates that the effect of S1P(1) on sprouting is EC-autonomous. Comparable
      vascular abnormalities in S1p(1) knockdown zebrafish embryos suggest cross
      species evolutionary conservation of this mechanism. Finally, genetic interaction
      between S1P(1) and Vegfa suggests that these factors interplay to regulate
      vascular development, as Vegfa promotes sprouting whereas S1P(1) inhibits it to
      prevent excessive sprouting and fusion of neovessels. More broadly, because S1P,
      the ligand of S1P(1), is blood-borne, our findings suggest a new mode of
      regulation of angiogenesis, whereby blood flow closes a negative feedback loop
      that inhibits sprouting angiogenesis once the vascular bed is established and
      functional.

PMID- 22951645
TI  - The WIF domain of the human and Drosophila Wif-1 secreted factors confers
      specificity for Wnt or Hedgehog.
AB  - The Hedgehog (Hh) and Wnt signaling pathways are crucial for development as well
      as for adult stem cell maintenance in all organisms from Drosophila to humans.
      Aberrant activation of these pathways has been implicated in many types of human
      cancer. During evolution, organisms have developed numerous ways to fine-tune Wnt
      and Hh signaling. One way is through extracellular modulators that directly
      interact with Wnt or Hh, such as the Wnt inhibitory factor (Wif-1) family of
      secreted factors. Interestingly, Wif-1 family members have divergent functions in
      the Wnt and Hh pathways in different organisms. Whereas vertebrate Wif-1 blocks
      Wnt signaling, Drosophila Wif-1 [Shifted (Shf)] regulates only Hh distribution
      and spreading through the extracellular matrix. Here, we investigate which parts
      of the Shf and human Wif-1 (WIF1) proteins are responsible for functional
      divergence. We analyze the behavior of domain-swap (the Drosophila and human WIF
      domain and EGF repeats) chimeric constructs during wing development. We
      demonstrate that the WIF domain confers the specificity for Hh or Wg morphogen.
      The EGF repeats are important for the interaction of Wif-1 proteins with the
      extracellular matrix; Drosophila EGF repeats preferentially interact with the
      glypican Dally-like (Dlp) when the WIF domain belongs to human WIF1 and with
      Dally when the WIF domain comes from Shf. These results are important both from
      the evolutionary perspective and for understanding the mechanisms of morphogen
      distribution in a morphogenetic field.

PMID- 22951646
TI  - [Investigation of SCCmec types and Panton-Valentine leukocidin in community
      acquired and nosocomial Staphylococcus aureus strains: comparing skin and soft
      tissue infections to the other infections].
AB  - Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are
      important health care problems since they are usually multidrug resistant.
      Although MRSA is isolated especially from nosocomial infections, community
      acquired MRSA infections are increasing. Methicillin resistance is due to the
      expression of mecA gene, which is located on SCCmec gene cassette. Different
      SCCmec types can be detected in hospital-acquired and community-acquired (CA-)
      MRSA strains. CA-MRSA strains might harbour Panton-Valentine leukocidin (PVL), an
      important virulence factor in skin and soft tissue infections. Strains carrying
      PVL has the ability to penetrate undamaged skin and cause more severe infections.
      The aim of this study was to detect SCCmec types and PVL gene in S.aureus strains
      isolated from skin and soft tissue infections and to compare with strains
      isolated from other infections in a university hospital in Ankara, Turkey.
      S.aureus strains isolated from skin and soft tissue infections (n= 285) and a
      control group consisting of 161 strains isolated from other infections (53 blood,
      48 lower respiratory tract samples, 30 sterile body fluids, 30 genitourinary
      tract samples) chosen by stratification and random selection method, were
      included in the study. Among skin and soft tissue infection strains 46.7% were
      from the hospitalized patients and 48.4% of skin and soft tissue infection
      strains were from female patients. The mean age of the skin and soft tissue
      infection patients was 45.5 years. Among the control strains 60.9% were from the
      hospitalized patients and 41.6% of the control patients were female. The mean age
      of the control patients was 50.2 years. Strains were identified by the Phoenix
      system (Becton Dickinson, USA) and identification was confirmed by tube coagulase
      test. Methicillin resistance was determined by the Phoenix system which
      determines both oxacillin and cefoxitin minimum inhibitor concentrations and,
      confirmed by oxacillin agar screening and/or cefoxitin disk diffusion test. All
      isolates were screened for the presence of mecA and PVL genes and SCCmec types
      were determined by PCR. MRSA constituted 20.3% (n= 58) of skin and soft tissue
      infection isolates and 24.2% (n= 39) of the control group. Of the 97 MRSA, 85 had
      a SCCmec type III-like pattern with an additional dcs region, three had type IV,
      three had type IIIa, one had type IIIb, one had type II and four could not be
      typed. The difference between SCCmec type distribution in skin and soft tissue
      infection and other infections' (control) groups was not statistically
      significant (p> 0.05). Two of the three SCCmec type IV strains were type IVa. Ten
      (2.2%) PVL positive strains, three of which were from the control group; were all
      methicillin susceptible S.aureus (MSSA). Although PVL positive MRSA was not
      common, detection of SCCmec type IVa, a marker for CAMRSA, and PVL positive MSSA
      strains which might act as a reservoir for PVL positive MRSA, indicated the
      importance of ongoing surveillance for MRSA.

PMID- 22951647
TI  - [Evaluation of antibiotic susceptibilities and VISA-VRSA rates among MRSA strains
      isolated from hospitalized patients in intensive care units of hospitals in seven
      provinces of Turkey].
AB  - The aim of this study was to determine whether vancomycin resistant
      Staphylococcus aureus (VRSA) and vancomycin intermediate susceptible S.aureus
      (VISA) strains were present among methicillin-resistant S.aureus (MRSA) strains
      isolated from patients hospitalised at intensive care units (ICU) of hospitals
      located at different regions of Turkey and to determine the minimum inhibitory
      concentration (MIC) values of teicoplanin, linezolid, tigecycline, quinupristin
      dalfopristin and daptomycin, which are alternative drugs for the treatment of
      MRSA infections. A total of 260 MRSA clinical strains (isolated from 113 lower
      respiratory tract, 90 blood, 24 wound, 17 catheter, 13 nasal swabs, two urine and
      one CSF sample) were collected from nine health-care centers in eight provinces
      [Ankara (n= 52), Konya (n= 49), Antalya (n= 40), Istanbul (n= 7), Izmir (37),
      Diyarbakir (n= 15), Van (n= 12), Trabzon (n= 48)] selected as representatives of
      the seven different geographical regions of Turkey. Methicillin resistance was
      determined by cefoxitin disk diffusion in the hospitals where the strains were
      isolated and confirmed by oxacillin salt agar screening at the Refik Saydam
      National Public Health Agency. Screening for VISA and VRSA was conducted using
      the agar screening test and E-test. Susceptibility of the MRSA strains to other
      antibiotics was also determined by E-test method. None of the 260 MRSA strains
      were determined to be VRSA or VISA. All were susceptible to teicoplanin and
      linezolid, and susceptibility rates to daptomycin, tigecycline and quinupristin
      dalfopristin were 99.6%, 96.9%, and 95%, respectively. Absence of VISA and VRSA
      among the MRSA strains surveyed currently seemed hopeful, however, continuous
      surveillance is necessary. In order to prevent the development of VISA and VRSA
      strains the use of linezolid, tigecycline, quinupristin-dalfopristin and
      daptomycin should be encouraged as alternative agents of treatment of MRSA
      infections.

PMID- 22951648
TI  - [In vitro activity of linezolid and dalbavancin against vancomycin-resistant
      enterococci].
AB  - The incidence of infections caused by multidrug resistant gram-positive bacteria
      is increasing worlwide. In addition, emergence and dissemination of glycopeptide
      resistance in enterococci has accelerated the need for the development of new
      antimicrobial agents for treatment. Linezolid which is an oxazolidinone and
      dalbavancin which is a second-generation, semi-synthetic lipoglycopeptid are
      important therapeutic options for infections caused by antimicrobial-resistant
      gram-positive pathogens. The aim of this study was to investigate the in-vitro
      antimicrobial activity of linezolid and dalbavancin against vancomycin- resistant
      enterococci (VRE). A total of 100 VRE strains, isolated from rectal swabs of
      patients hospitalized in Istanbul University Faculty of Istanbul Medicine between
      2006-2007 were included in the study. All strains were identified as Enterococcus
      spp. by conventional methods and had minimum inhibitory concentrations (MICs) of
      >= 32 ug/ml for vancomycin. Vancomycin, linezolid and dalbavancin susceptibility
      testing was performed by broth microdilution method. For the quality control of
      the tests, S.aureus ATCC 29213 and E.faecalis ATCC 29212 were included in each
      run. Molecular identification of linezolid-resistant strains (n= 2) were done by
      16S rRNA sequencing and resistance mechanisms were tested by 23S rRNA sequencing.
      Against VRE strains, MIC50, MIC90 and MIC ranges of linezolid and dalbavancin
      were found as 4, 4, 1-16 ug/ml and 32, 64, 0.25-128 ug/ml, respectively.
      Linezolid susceptibility, intermediate susceptibility and resistance rates were
      found as 32%, 66% and 2% in the same order. Linezolid-resistant two strains were
      identified as E.faecium, and this data was confirmed by Pasteur Institute. Both
      of those isolates had G2576T mutations in 23S rRNA genes. Because susceptibility
      breakpoint for dalbavancin has not been established by Clinical and Laboratory
      Standards Institute (CLSI) yet, susceptibility and resistance rates for
      dalbavancin were not indicated. According to the MIC results, linezolid was found
      to be the most effective antibiotic against VRE strains, and dalbavancin was
      found more effective than vancomycin. Additionally, our results showed that
      routine susceptibility testing of VRE strains isolated from hospitalized patients
      to linezolid was required.

PMID- 22951650
TI  - [Detection of plasmid-mediated AmpC beta-lactamase in clinical isolates of
      cefoxitin-resistant Escherichia coli and Klebsiella pneumoniae].
AB  - Extended spectrum beta-lactamases (ESBL) or AmpC beta-lactamases may be
      associated with false cephalosporin susceptibility results. Although there are
      well-established methods for screening and confirmation of class A (ESBL) and
      class B metallobeta-lactamases (MBL), there is no current guideline for the
      detection of AmpC beta-lactamases. The aim of this study was to evaluate the
      performances of three different phenotypic tests [boronic acid (BA) - klavulanic
      acid (CA) inhibition test, AmpC disk test (TRISEDTA impregnanted), modified 3
      dimensional test (M3DT)] for the detection of AmpC beta-lactamases. A total of 50
      (42 were Escherichia coli and eight were Klebsiella pneumoniae) cefoxitin
      insusceptible strains were collected during June-September 2009. Multiplex PCR
      was used as the genotypic confirmation test by using DHA, CIT, MOX, FOX and EBC
      primers. Twenty-five (50%) of 50 cefoxitin-insusceptible strains yielded positive
      result by BA-CA test. Twenty two (88%) of 25 BA-CA positive strains yielded
      positive result by multiplex PCR and all of them belonged to CIT family (CMY-2 to
      CMY-7, LAT-1 to LAT-4 and BIL-1 type) of AmpC beta-lactamases. One strain
      harboured both CIT and EBC family of AmpC beta- lactamases, one strain harboured
      CIT + MOX + ESBL. DHA and FOX family of AmpC beta-lactamases were not detected in
      this study. Both AmpC disk test and M3DT yielded positive test with 11 (52.3%) of
      21 AmpC enzyme producing strains (except for one of the PCR positive strain which
      couldn't be screened by M3DT and AmpC disk test). When BA was added to CA
      inhibition test, the number of positive isolates of ESBL increased from 13 to 14
      (63.6%) due to inhibition of AmpC with BA. Hovewer, the strains which yielded
      negative results by 3-aminophenylboronic acid (3-APB) were tested again by
      benzeneboronic acid. Three strains were also found to be positive with
      benzeneboronic acid. The results of this study indicated that BA test with
      benzene boronic acid or 3-APB warranted further study. In conclusion, for the
      phenotypic detection of AmpC beta-lactamases, BA-CA test is simple to perform and
      easy to interpret. Briefly, in order to prevent the masking effect of ESBL, CA
      must be added to the BA inhibition test. Also in order to prevent the masking
      effect of AmpC beta-lactamases on ESBL detection, BA must be added to the CA
      inhibition test.

PMID- 22951649
TI  - [Investigation of plasmid-mediated quinolone resistance determinants in
      Enterobacteriaceae: a multicenter study].
AB  - Fluoroquinolones which are in use since 1986, are effective agents both against
      gram-positive and gram-negative bacteria. Quinolones show bactericidal effect as
      a result of inhibition of DNA gyrase and topoisomerase IV enzymes. Main quinolone
      resistance mechanisms are chromosomal mutations in these enzymes and decreased
      intracellular accumulation due to efflux pumps or decreased membrane uptake.
      Recently a new quinolone resistance mechanism mediated by plasmids has been
      defined. These plasmids carry genes called as qnr. Qnr genes do not cause
      quinolone resistance but they cause decreased quinolone susceptibility and lead
      to higher minimum inhibitory concentrations. Currently there are qnrA, qnrB,
      qnrC, qnrD and qnrS genes. This study was aimed to investigate the presence of
      plasmid-mediated quinolone resistance determinants in Enterobacteriaceae isolates
      collected from four different centers in Turkey. A total of 647 isolates (387
      from Trabzon, Black Sea region; 82 from Canakkale, Trace region; 96 from Ankara,
      Central Anatolia region; 82 from Tokat, Black Sea region) belonging to the
      Enterobacteriaceae family collected between May-July 2009, were included in the
      study. Presence of qnrA, qnrB, qnrS and qnrC genes were investigated by multiplex
      polymerase chain reaction (PCR) method and confirmed by gene sequencing. The
      results of the PCR amplification revealed that 2 isolates were positive for qnrA,
      12 isolates were positive for qnrB, 4 isolates were positive for qnrC and 10
      isolates were positive for qnrS. However, the number of positive strains
      decreased with the use of gene sequencing, and this method led to the
      identification of qnrA1 in two isolates [Enterobacter cloacae (code. 796),
      Salmonella group B (code. 491)], qnrB1 in two isolates [Salmonella group B (code.
      491), Citrobacter freundii (code. 768)], qnrB6 in one isolate [Escherichia coli
      (code. CC1800)], qnrB9 in one isolate [E.coli (code. CC1873)], qnrB24 in one
      isolate [Citrobacter koseri (code. MP5200)], qnrB27 in one isolate [C.freundii
      (code. 842)], qnrS1 in two isolates [E.coli (code. CC1705), E.coli (code.159)]
      and qnrB2 in one isolate [E.coli (code. 843)]. One of the isolates that carried
      the qnr gene was ciprofloxacin-resistant and two isolates were nalidixic-acid
      resistant. Transferable quinolone resistance due to the dissemination of qnr
      genes may have important impacts in terms of infection control and treatment
      problems. Survey of plasmid mediated quinolone resistance will help to determine
      the size of the issue and guide the measures that should be taken to avoid
      escalation of resistance and dissemination problem.

PMID- 22951651
TI  - [Antibiotic susceptibility rates and beta-lactam resistance mechanisms of
      Pseudomonas aeruginosa strains].
AB  - Pseudomonas aeruginosa is a well-known cause of severe and potentially life
      threatening infections including bacteremia, skin and wound infections, pulmonary
      disease, especially among individuals with cycstic fibrosis, nosocomial urinary
      tract infections, endocarditis and meningitis. The mechanism of resistance to
      broad-spectrum beta-lactams in P.aeruginosa are overexpression of
      cephalosporinases and/or class A, B and D beta-lactamases. Recently PER-1 type
      beta-lactamase has been reported from Turkey, France, Italy, Romania, Hungary,
      Belgium, Russia, South Korea and India. OXA beta-lactamases have increasingly
      been reported in clinical strains of P.aeruginosa from various geographical
      origins. This study was aimed to investigate the antibiotic susceptibility of
      various P.aeruginosa clinical strains and to define the beta-lactamase enzymes
      leading to resistance. In this study, a total of 100 P.aeruginosa strains
      isolated from various clinical specimens (37 urine, 21 blood, 10 sputum, 5
      bronchoalveolar lavage, 5 abscess, 5 wound swabs, 4 endotracheal aspirate, 3
      throat swabs, 2 catheter tips, one of each pleural and peritoneal fluid) were
      included. According to Clinical and Laboratory Standards Institute (CLSI)
      recommendations, susceptibilities of isolates to various antibiotics were
      investigated by disk diffusion and agar dilution method, and beta-lactamase
      enzymes were detected by isoelectric focusing (IEF) method. PSE, PER-1, OXA-10
      like beta-lactamase genes and MEX-R genes of isolates were investigated by
      polymerase chain reaction (PCR). According to MIC90 values, the most effective
      antibiotics were found to be imipenem (8 ug/ml). The MIC90 values of amikacin,
      ciprofloxacin, cefepime, cefpirome, piperacillin + tazobactam, piperacillin,
      ceftazidime, ticarcilin, aztreonam and ticarcilin + clavulanic acid were 32, 64,
      64, 64, 128/4, 512, 512, 512, 512 and 512/2 ug/ml, respectively. Seven of the
      isolates were found to be ESBL positive by double-disk synergy method. It was
      detected that 10% of the isolates were imipenem-susceptible and 9% were
      intermediate susceptible. Phenotypical investigation of metallo-beta-lactamase
      enzyme in these strains by MBL E-test method did not reveal a positive result.
      PER-1 and OXA-10 like beta-lactamases were detected each in 11% of the isolates,
      and co-presence of PER-like and OXA-10 like enzymes were shown in 4% of the
      isolates. PSE gene was not found in any of the strains. The MEXR gene was
      identified in 52% of the isolates. Antibiotic resistance mechanisms in
      P.aeruginosa strains seems to be complex. Determination of the resistance
      mechanisms and antibiotic susceptibility rates in P.aeruginosa will guide the
      proper antimicrobial therapy, reducing the emergence of resistant strains.

PMID- 22951652
TI  - [Detection of Helicobacter pylori and antimicrobial resistance in gastric biopsy
      specimens].
AB  - Helicobacter pylori is reported as the etiological agent of gastritis, gastric
      and duodenal ulcer, gastric adenoid carcinoma and mucosa-associated lymphoid
      tissue lymphoma. In the diagnosis of H.pylori infections invasive (culture,
      histopathological examination, rapid urease test and molecular tests) and non
      invasive (urea breath test, serological tests, stool culture and stool
      antigen/nucleic acid tests) methods may be used. Clarithromycin, amoxicillin and
      combination of metronidazole and protonpump inhibitor or ranitidine bismuth
      citrate triple treatment protocol is applied in order to treat and eradicate the
      infection. However, increasing rates of antibiotic resistance among H.pylori
      strains reduces the success of eradication therapy. The aim of this study was to
      investigate the presence of H.pylori in the gastric antral biopsy specimens and
      to determine the antimicrobial resistance of the isolates. A total of 149 gastric
      antral biopsy specimens obtained from patients (age range: 17-83 years; 73 were
      male) who admitted to Mersin University Faculty of Medicine Department of
      Internal Medicine Gastroenterology clinic with dyspeptic complaints were included
      in the study. H.pylori presence was investigated by culture, polymerase chain
      reaction (PCR) and urease test from gastric biopsy specimens, and H.pylori
      specific antigen (HpSA) was investigated by ELISA in the stool samples of
      patients. Resistance to tetracycline, amoxicillin, metronidazole and levofloxacin
      was determined with E-test method. Clarithromycin resistance was determined both
      by E-test and PCR-RFLP (restriction fragment length polymorphism) methods.
      H.pylori was detected in 29.6% (43/145) of patients with culture, 55.2% (80/145)
      of patients with urease test, 57% (65/114) of patients with HpSA test and 71.3%
      (102/143) of patients with PCR. The sensitivity and specificity of culture, PCR,
      HpSA and urease tests were determined as 52.4% and 100%, 96.3% and 62.3%, 80.3%
      and 81.4%, 86.6% and 85.7%, respectively. According to the E-test results,
      resistance to clarithromycin was 18.2%, to tetracycline 9.1%, to metronidazole
      45.5%, to levofloxacin 18.2% and no resistance was determined to amoxicillin.
      Clarithromycin resistance was searched in 94 of PCR positive 102 samples, and 17
      (18.1%) of them yielded clarithromycin resistance. Of them 11 (64.7%) harbored
      A2144G (at 2144. nucleotide), and 6 (%35.3) harbored A2143G (at 2143. nucleotide)
      point mutations. In our study, PCR was determined as the most sensitive method,
      however due to its low specificity, the results should be confirmed with at least
      one of the other methods. The specificity of culture method was high, but
      sensitivity was found to be quite low compared with other methods. The
      sensitivity and specificity of urease and HpSA tests were found to be similar. In
      conclusion, in cases which endoscopy could not be done, non-invasive, rapid and
      practical HpSA method can be used in diagnosis and monitorization of the
      treatment. In the case of treatment failure, culture should be performed for
      antibiotic susceptibility testing of the isolate.

PMID- 22951653
TI  - [Do different interpretative methods used for evaluation of checkerboard synergy
      test affect the results?].
AB  - In recent years, owing to the presence of multi-drug resistant nosocomial
      bacteria, combination therapies are more frequently applied. Thus there is more
      need to investigate the in vitro activity of drug combinations against multi-drug
      resistant bacteria. Checkerboard synergy testing is among the most widely used
      standard technique to determine the activity of antibiotic combinations. It is
      based on microdilution susceptibility testing of antibiotic combinations.
      Although this test has a standardised procedure, there are many different methods
      for interpreting the results. In many previous studies carried out with multi
      drug resistant bacteria, different rates of synergy have been reported with
      various antibiotic combinations using checkerboard technique. These differences
      might be attributed to the different features of the strains. However, different
      synergy rates detected by checkerboard method have also been reported in other
      studies using the same drug combinations and same types of bacteria. It was
      thought that these differences in synergy rates might be due to the different
      methods of interpretation of synergy test results. In recent years, multi-drug
      resistant Acinetobacter baumannii has been the most commonly encountered
      nosocomial pathogen especially in intensive-care units. For this reason,
      multidrug resistant A.baumannii has been the subject of a considerable amount of
      research about antimicrobial combinations. In the present study, the in vitro
      activities of frequently preferred combinations in A.baumannii infections like
      imipenem plus ampicillin/sulbactam, and meropenem plus ampicillin/sulbactam were
      tested by checkerboard synergy method against 34 multi-drug resistant A.baumannii
      isolates. Minimum inhibitory concentration (MIC) values for imipenem, meropenem
      and ampicillin/sulbactam were determined by the broth microdilution method.
      Subsequently the activity of two different combinations were tested in the
      dilution range of 4 x MIC and 0.03 x MIC in 96-well checkerboard plates. The
      results were obtained separately using the four different interpretation methods
      frequently preferred by researchers. Thus, it was aimed to detect to what extent
      the rates of synergistic, indifferent and antagonistic interactions were affected
      by different interpretation methods. The differences between the interpretation
      methods were tested by chi-square analysis for each combination used.
      Statistically significant differences were detected between the four different
      interpretation methods for the determination of synergistic and indifferent
      interactions (p< 0.0001). Highest rates of synergy were observed with both
      combinations by the method that used the lowest fractional inhibitory
      concentration index of all the non-turbid wells along the turbidity/non-turbidity
      interface. There was no statistically significant difference between the four
      methods for the detection of antagonism (p> 0.05). In conclusion although there
      is a standard procedure for checkerboard synergy testing it fails to exhibit
      standard results owing to different methods of interpretation of the results.
      Thus, there is a need to standardise the interpretation method for checkerboard
      synergy testing. To determine the most appropriate method of interpretation
      further studies investigating the clinical benefits of synergic combinations and
      additionally comparing the consistency of the results obtained from the other
      standard combination tests like time-kill studies, are required.

PMID- 22951654
TI  - [Comparison of endotracheal aspiration and mini-BAL culture results in the
      diagnosis of ventilator-associated pneumonia].
AB  - The objective of this study was to compare the results of cultures obtained by
      mini-bronchoalveolar lavage (BAL) and endotracheal aspiration (ETA) techniques,
      used for rapid and accurate determination of pathogens causing ventilator
      associated pneumonia (VAP) in intensive care units. Of the 92 patients on
      mechanical ventilation followed at the emergency intensive care unit of our
      hospital between June 2010 and June 2011, 30 (32.2%) patients were diagnosed as
      VAP and they were included in this study. VAP diagnosis were based on the
      clinical and radiological findings. Clinical pulmonary infection score (CPIS) of
      > 6 was accepted as the clinical criteria of VAP. Initially ETA samples were
      collected from the patients followed by mini-BAL sampling 15 minutes later,
      together with urine and two blood cultures. Microbiological evaluation and
      identification were performed by conventional methods and Phoenix 100 (BD
      Diagnostic Systems, ABD) automated system. In quantitative culture analysis, >
      10.000 cfu/ml for BAL and > 100.000 cfu/ml for ETA were accepted as the positive
      result. The mean ages of VAP-developed (n= 30; 18 were male) and nondeveloped (n=
      62; 39 were male) patients were 68.23 +/- 16.19 and 52.16 +/- 10.41 years,
      respectively, and the mean durations of mechanical ventilation were 29.57 +/-
      15.78 and 12.11 +/- 6.01 days, respectively. Multivariate logistic regression
      analysis showed that older age (p< 0.001) and duration of mechanical ventilation
      (p< 0.001) were independent risk factors for VAP development. There was also a
      statistically significant difference in CPIS values between patients who
      developed VAP and not (6.8 +/- 1.15 and 2.71 +/- 1.06, respectively; p< 0.001).
      The use of CPIS for VAP diagnosis was found to be useful in patients on
      mechanical ventilation. In our study, a total of 16 strains (six A.baumannii,
      three P.aeruginosa, one K.pneumoniae, six S.aureus) were isolated from ETA
      cultures, while 34 strains (16 A.baumannii, six P.aeruginosa, four K.pneumoniae,
      two E.coli, six S.aureus) were isolated from mini-BAL cultures of 30 VAP
      patients. The contamination rate for ETA cultures was found as 27% (8/30),
      however there was no contamination in mini-BAL samples. The rates of negative
      cultures for ETA and mini-BAL were 20% (6/30) and 7% (2/30), respectively. Seven
      (87.5%) of the eight contaminated ETA samples, yielded pathogenic bacterial
      growth (six A.baumannii, one K.pneumoniae) in mini-BAL samples. Similarly, of the
      six negative ETA samples, 5 (83%) yielded bacterial growth (two E.coli, two
      K.pneumoniae, one P.aeruginosa) in mini-BAL samples. Statistical analysis with
      Spearman test indicated no positive correlation between the culture results of
      mini-BAL and ETA (p= 0.464), and the concordance between the culture results of
      those methods was found as 50%. It was concluded that the use of mini-BAL instead
      of ETA samples for the isolation of causative microorganisms of VAP seemed to be
      more useful due to the high contamination risk in ETA culturing techniques and
      higher bacterial isolation rates in mini-BAL sampling.

PMID- 22951655
TI  - [Determination of hepatitis B virus genotypes in chronic hepatitis B patients in
      Mersin province, Turkey].
AB  - Currently, ten genotypes (A-J) of hepatitis B virus (HBV) are identified based on
      the nucleic acid sequence heterogeneity, and these genotypes have been shown to
      have distinct geographic distribution. Reports of previous studies indicated that
      the genotype D is the predominant type among hepatitis B patients in different
      regions of Turkey, however there is no data for HBV genotypes to date from Mersin
      region. The aim of this study was to investigate the HBV genotypes by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) in chronic
      hepatitis B patients in Mersin province (located in the Mediterranean region of
      Turkey). A total of 54 serum samples were obtained from the chronic hepatitis B
      patients (33 male, 21 female; mean age: 40.05 years) followed-up at
      Gastroenterology Clinic of Mersin University Hospital. Patients had detectable
      HBV-DNA levels in their serum samples, and they were under antiviral therapy for
      at least one year. Genotyping of HBV was performed by RFLP analysis with the use
      of AvaII and MboI restriction enzymes after amplification of pre-S gene region by
      PCR. Confirmation of selected 18 cases was carried out with direct DNA
      sequencing. The genotypes were determined by phylogenetic comparison with 43
      reference NCBI (National Center for Biotechnology Information) HBV sequences.
      Genotype determination was not successful in seven cases; since three of them
      were negative in preS-PCR, three of them yielded non-specific bands, and one of
      them exhibited a deleted PCR product, at the 300 bp level that was shorter than
      expected. Four different restriction patterns were determined in PCR-RFLP
      analysis of the remaining 47 samples. One of these patterns which was AvaII [
      ]/MboI [306/89/51], was clearly discriminated in 72.3% (34/47) of the samples as
      genotype D. Genotype discrimination of three patterns could not be done properly
      and these patterns were AvaII [- ]/MboI [357/306/89/51] (7/47, 14.9%), AvaII
      [300/146]/MboI [306/89/51] (5/47, 10.7%), and AvaII [- ]/MboI [357/89/---] (1/47,
      2.1%). Phylogenetic comparison of HBV sequences demonstrated that all patterns in
      our cases were clustered in NCBI genotype D sequences. Patterns of AvaII
      [300/146]/MboI [306/89/51] and AvaII [-]/ MboI [357/89/---] and deleted sample
      were recognized as pre-S gene variants of HBV isolates. Our data indicated that
      the predominant HBV type was genotype D as commonly seen in Turkey and other
      Mediterranean countries. The results of this study also showed that the genotype
      uniformity and pre-S gene variants within the HBV isolates could be crucial in
      terms of understanding the molecular epidemiology of HBV circulating in the
      Mediterranean region of Turkey.

PMID- 22951656
TI  - [Investigation of combined effectiveness of spiramycin and beta-glucan in mice
      models of acute toxoplasmosis and determination of IL-10, IL-12 and TNF-alpha
      levels].
AB  - Toxoplasmosis which is caused by Toxoplasma gondii, has a high risk of fetal
      infection development if the infection occurs during pregnancy. Treatment with
      oral spiramycin is recommended during pregnancy in order to prevent the
      transmission of protozoa to fetus and development of infection. Since beta-
      glucan is known to stimulate the immune system and increase the phagocytic
      activity of the cells, it has been shown to exhibit immunomodulatory effect on
      many infectious diseases. The objectives of this study were to investigate the
      effectiveness of beta-glucan alone and in combination with spiramycin and to
      determinate the levels of interlokin (IL)-10, IL-12 and tumor nekrosis factor
      (TNF)-alpha in mice experimentally infected with T.gondii. For this purpose, four
      experimental groups each consisting of eight BALB/c mice, were formed with the
      approval of Ethics Committee for the Animal Experiments. All the mice were
      infected with 2 ml of suspension containing 2 x 102/ml of trophozoite prepared
      from T.gondii RH strain (Refik Saydam National Public Health Agency, Parasitology
      Laboratory of Communicable Diseases Research Department, Ankara, Turkey), by
      intraperitoneal injection. Twenty-four hours after the infection, beta-glucan (3
      mg/day) was given to the beta-glucan group, spiramycin (200 mg/kg/day) to the
      spiramycin group, beta-glucan (3 mg/day) plus spiramycin (200 mg/kg/day) to the
      beta-glucan-spiramycin (BG-S) group by oral gavage. The fourth group which was
      the control group was infected but untreated. The above administration was
      carried out for seven days. On the 8th day, under anaesthesia, 1 ml normal saline
      was given into the peritoneum, drawn back later and the number of trophozoites in
      1 ml of peritoneal fluid was determined by counting them on the Thoma slide.
      Moreover, by drawing the heart blood; IL-10, IL-12, TNF-alpha levels were
      determined in serum samples by ELISA method (eBioscience Platinum, Austria). The
      number of trophozoites in the BG-S group was found significantly lower than the
      number of trophozoites in control, beta-glucan and spiramycin groups (p< 0.05).
      There was no significant difference between the beta-glucan and spiramycin
      groups, however the number of trophozoites in both groups was significantly lower
      than the number of trophozoites in the control group (p< 0.05). There was a
      certain decrease in IL-10 level in spiramycin and BG-S groups, compared to the
      control group, in addition when IL-10 levels in spiramycin and BG-S groups were
      compared with BG group, a significant decrease was noticed (p< 0.05). There was
      no difference in IL-12 levels between the groups, while there was a certain
      decrease in TNF-alpha level in beta-glucan, spiramycin, BG-S group in comparison
      to the control group. Within the reach of our literature survey, this study is
      the first research in which the effectiveness of the combination of beta-glucan
      and spiramycin in the treatment of acute toxoplasmosis was investigated. The
      results of our study suggested that there might be synergy between beta-glucan
      and spiramycin in the treatment of acute toxoplasmosis.

PMID- 22951657
TI  - [Evaluation of Trichinella cross-reactions in the serological diagnosis of
      toxocariasis].
AB  - Toxocariasis caused by the nematode larvae of the Toxocara genus is a worldwide
      parasitic zoonosis. Diagnosis of human toxocariasis commonly relies on
      serological tests since the symptoms and signs of Toxocara infection are not
      pathognomonic. However Toxocara larval excretory-secretory (TES) antigen used in
      serological tests may exhibit low specificity due to the cross-reactions between
      related helminth infections such as ascariasis, anisakiasis, strongyloidosis and
      filariasis. In this study, we aimed to evaluate the possible effect of
      Trichinella cross-reactions in the serological diagnosis of toxocariasis by using
      ELISA and Western blot (WB) assay. For this purpose, sera samples of 209
      trichinellosis patients who were definitely diagnosed during the Trichinella
      britovi outbreak occurred in Izmir in January 2004, were used. All the samples
      were screened initially by commercial Toxocara IgG-ELISA kit (Cypress
      Diagnostics, Belgium), then commercial Toxocara IgG-WB (Test-Line Diagnostics,
      Czech Republic) was applied to positive/ borderline-positive sera for
      confirmation. In our study, 94.3% (197/209) of the sera were found seronegative,
      while nine were positive and three were borderline. Thus a total of 12 (5.7%)
      sera were considered as seropositive by Toxocara IgG-ELISA. According to the
      results of WB, only one sera with the antigenic bands of 120 kDa, 32 kDa and 26
      kDa in molecular weights was evaluated as positive. Four sera samples were found
      to be borderline. In three of border sera, the antigenic bands of 120 and 70 kDa
      in molecular weights were observed together and one sera had three (120, 70 and
      32 kDa) different antigenic bands. Seven sera that had been found to be positive
      by ELISA was considered as negative by WB. While no bands was observed in four of
      these, three samples had an antigenic band of 120 kDa which had no diagnostic
      value when it was found alone. The results of our study showed that the
      crossreactivities between anti-Trichinella antibodies and TES antigens may be
      observed during Toxocara IgG ELISA assay. For that reason the positive Toxocara
      IgG-ELISA result should be confirmed by different tests such as WB for the
      definitive diagnosis of toxocariasis.

PMID- 22951658
TI  - [Investigation of West Nile virus RNA in blood donors by real-time RT-PCR].
AB  - West Nile virus (WNV), a member of Flaviviridae family, is an enveloped,
      icosahedral symmetric RNA virus. Primary reservoir hosts of WNV are birds, but
      the virus can cause various infections in humans and other mammals. The most
      common and natural transmission way of WNV infections is mosquito bites, however,
      humans can be infected by different routes. The most important non-mosquito
      transmission route is contaminated blood and blood products. In this study, we
      aimed to investigate the risk of WNV transmission through blood and blood
      products in Ankara, Turkey. The presence of WNV RNA was investigated by in house
      real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in serum
      samples obtained from 729 healthy blood donors (mean age: 27.7 years; 711 were
      male), regardless of the donor's seropositivity status since the virus can be
      transmitted at the early stages of infection when seroconversion has not yet
      developed. Serum samples were collected in August-September 2009, the period when
      these infections are more frequent due to mosquito activity. The vast majority of
      donors (n= 702, 96.3%) have been inhabiting in Ankara and 569 (78%) of donors
      have had risk factors for arboviral infections (e.g. outdoor activity, mosquito
      and tick bites). WNV RNA was not detected by real-time RT-PCR analysis in any
      serum sample included in this study. According to the results of our study, it
      can be said that the risk of WNV transmission through blood and blood products is
      low in Ankara. However, WNV seropositivity was detected within the range of 0.56
      to 2.4% among blood donors in previous studies and probable and confirmed WNV
      infections have been reported in our region. In addition, WNV outbreaks have
      emerged in some countries neighbouring Turkey recently. Thus, the risk of WNV
      transmission through blood and blood products should not be ignored and blood
      donor questionnaires should be evaluated in detail.

PMID- 22951659
TI  - [Treatment of hemodialysis catheter-associated bacteremia due to methicillin
      resistant Staphylococcus aureus by daptomycin lock method].
AB  - Treatment of catheter-associated infections caused by Staphylococcus aureus is
      difficult without catheter removal, because of the biofilm formation and its high
      virulence. In this report, we presented our clinical and microbiological
      experience with systemic daptomycin (6 mg/kg/on alternate days IV) as well as
      antibiotic lock therapy (filling of the catheter lumen with 3.5 mg/ml daptomycin
      together with 0.045 mg/ml calcium) in the treatment of a catheter-associated
      bloodstream infection caused by methicillin-resistant S.aureus in a patient with
      hemodialysis catheter which could not be removed.

PMID- 22951660
TI  - [A case of brucellosis misdiagnosed as Crimean-Congo hemorrhagic fever].
AB  - Brucellosis which is a zoonotic infection, is an important public health problem
      in Turkey and all over the world. The disease may involve many organs and
      systems. Since the symptoms of brucellosis are non-specific, difficulties in
      differential diagnosis and misdiagnosis are frequent. In this case report we
      present a case of brucellosis, misdiagnosed as Crimean-Congo hemorrhagic fever
      (CCHF). A 13-year-old boy was referred from another medical center with
      preliminary diagnosis of CCHF and admitted to our clinic with fever and a history
      of presence of a tick on his back. His physical observation only included
      splenomegaly. The laboratory results on admission were anemia, thrombocytopenia,
      elevation of acute phase reactants and liver transaminase levels. Abdominal
      ultrasonography revealed splenomegaly. Since the patient had anemia, epistaxis,
      fever and thrombocytopenia, he was initially diagnosed as CCHF. Meantime serum
      sample of the patient had been sent to Refik Saydam National Public Health Agency
      for CCHF PCR test. The fever of the patient could not be controlled. His detailed
      medical history revealed stockbreeding and consumption of raw milk products.
      Patient's signs and symptoms were also compatible with brucellosis and standard
      tube agglutination test for brucellosis was positive at 1/1280 titer in serum.
      The patient was diagnosed as brucellosis and the treatment was started with
      combination of rifampicin (1 x 600 mg/day) and doxycycline (2 x 100 mg/day).
      Blood cultures yielded negative result. The PCR tests for CCHF was found also
      negative. His fever and other complaints improved with treatment which was
      completed in six weeks and the follow-up was without complications. Turkey is
      endemic both for brucellosis and CCHF. This case was reported to emphasize that
      the cases of brucellosis could mimic other diseases and brucellosis should also
      be considered in the differential diagnosis of CCHF.

PMID- 22951661
TI  - [Two cases of acute hepatitis associated with Q fever].
AB  - Q fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many
      species of wild and domestic mammals, birds, and arthropods, are reservoirs of
      C.burnetii in nature, however farm animals are the most frequent sources of human
      infection. The most frequent way of transmission is by inhalation of contaminated
      aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q
      fever may present as acute or chronic disease. In acute cases, the most common
      clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and
      pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with
      Q fever has rarely been described in the literature. Herein we report two cases
      of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who
      inhabited in Malkara village of Tekirdag province (located at Trace region of
      Turkey), were admitted to the hospital with the complaints of persistent high
      grade fever, chills and sweats, icterus, disseminated myalgia and headache.
      Physical examination revealed fever, icterus and the patient appeared to be
      mildly ill but had no localizing signs of infection. Radiological findings of the
      patients were in normal limits. Laboratory findings revealed leukocytosis,
      increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia-
      mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte
      sedimentation rate were found normal. Blood and urine cultures of the patients
      yielded no bacterial growth. Serological markers for acute viral hepatitis,
      citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis,
      toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of
      the cases were based on the positive results obtained by C.burnetii Phase II IgM
      and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were
      confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both
      cases were treated with doxycycline for 14 days and became afebrile within four
      days. These cases were presented to emphasize that C.burnetii infection should be
      considered in the differential diagnosis of patients with fever and elevated
      serum transaminase levels, irrespective of the presence of abdominal pain and
      exposure to potentially infected animals.

PMID- 22951662
TI  - [A fatal case of West Nile virus encephalitis].
AB  - Although West Nile virus (WNV) serologic evidence has been well demonstrated
      throghout Turkey in the last 40 years; the first symptomatic WNV infection was
      reported in 2009 and increased number of cases were reported during August 2010.
      In that period WNV encephalitis was diagnosed serologically (WNV IgM positivity
      in serum sample detected by ELISA and IFA) and confirmed by plaque reduction
      neutralization test in a 76-year-old man who was admitted to Baskent University
      Faculty of Medicine with complaints of fever, impaired consciousness and
      generalized tremors. Despite all supportive treatment, he died on the 9th day of
      hospitalization. In this report, detailed clinical course, laboratory features
      and diagnosis of this mortal case of WNV encephalitis were described. WNV
      encephalitis should be considered in the differential diagnosis of patients with
      fever of unknown origin and loss of consciousness especially in summer and early
      fall in Turkey.

PMID- 22951663
TI  - [A severe falciparum malaria case successfully treated by exchange transfusion as
      an adjunct therapy].
AB  - Plasmodium falciparum malaria is a type of malaria with high fatality rate
      despite optimal antimalarial treatment. Exchange transfusion (ET) is successfully
      used as a means of supportive therapy in severe P. falciparum malaria cases with
      hyperparasitemia. Herein, we present a case with hyperparasitemia, who received
      erythrocyte ET therapy due to lack of clinical response to antimalarial
      treatment. A 24-year-old male patient was admitted to our emergency clinic with
      the complaints of fever that persisted for 10 days, headache, nausea-vomiting,
      and impaired consciousness. Medical history revealed that he had been working in
      Sudan, Africa and returned back 12 days ago. On physical examination; he had
      fever, hypotension, tachycardia, subicterus and impaired cooperation. Laboratory
      examination revealed pancytopenia, elevated C-reactive protein,
      hyperbilirubinemia, hyponatremia, elevated creatinine level and hematuria. On
      thick blood smear and thin blood smear examinations, multiple (> 5%) trophozoites
      and gametocytes indicating P.falciparum species were observed. The case was
      diagnosed as P.falciparum malaria and parenteral fluid support, dopamine
      infusion, meropenem (IV), doxycycline (PO) and quinine sulphate (PO) were
      initiated in the intensive care unit. On reevaluation of the patient on the third
      day of hospitalization, it was observed that arterial hypotension and fever were
      persistent, anemia and trombocytopenia deteriorated and on thick blood smear
      parasitemiea was not decreased. It was decided to apply automated erythrocyte ET.
      After ET, patient's medical status was quickly improved and patient was
      discharged on the 7th day of hospitalization. In conclusion, it was noted that in
      addition to antimalarial treatment, erythrocyte ET may provide dramatic
      improvement in severe cases of P.falciparum malaria with hyperparasitemia.

PMID- 22951664
TI  - [A case of cutaneous leishmaniasis caused by Leishmania infantum in a non-endemic
      province (Ankara) of Turkey].
AB  - Southeastern Anatolia and the Mediterranean regions of Turkey are known as
      endemic areas for cutaneous leishmaniasis (CL). In this report, a 64 years-old
      male patient with CL caused by Leishmania infantum has been presented. The
      patient who was inhabiting in Ankara (Central Anatolia region, Turkey) complained
      from a lesion on his right ring finger for the last six months. He has a cat and
      has been engaged with gardening. Overall, he was healthy with the exception of
      hypertension and glucose intolerance. The patient had not left Ankara since the
      last seven months, however, he had previously been to the Aegean coast during his
      summer holiday. The examination of the 4th phalanx of his right hand revealed the
      presence of a 3 x 3 cm erythematous, slightly swollen lesion, at the center of
      which 1.5 x 1.5 cm ulcerative area covered with a hemorrhagic crust, was
      detected. Neither axillary or cervical lymphadenopathy, nor hepatosplenomegaly
      could be observed. The routine examinations, including complete blood count,
      serum biochemistry, chest X-ray and abdominal ultrasonography were within normal
      limits. Giemsa stained smears prepared from aspiration of the lesion revealed
      amastigote-like organisms and leishmania promastigotes were grown in NNN media.
      PCR amplification of the specimen indicated the presence of a positive DNA band
      of 420 bp specific for Leishmania spp. The serum sample of the patient revealed
      positivity for leishmaniasis by the rapid rK39 test and immunofluorescence
      antibody (IFAT) test. The organism was identified as L.infantum by PCR-RFLP
      applied to the cultivated organism. The examination of his cat's serum for
      leishmaniasis by IFAT and PCR, were negative. The exact way of transmission had
      not been confirmed for the patient. However, when long incubation period of CL
      was considered, the transmission might probably occurred during his summer stay
      in the Aegean coast. This case was presented to withdraw attention to a delayed
      diagnosis of CL which developed in a non-endemic area and which was due to
      L.infantum instead of the more common L.tropica species.

PMID- 22951665
TI  - [Genomic organization and proteins of human papillomavirus].
AB  - Human papillomavirus (HPV) infections are one of the most common sexually
      transmitted diseases worldwide. Nowadays, more than 200 HPV types have been
      identified by DNA sequencing. HPV types are also grouped into three, such as high
      risk (types 6, 11, 40, 42, 43, 44, 54, etc), probable high-risk (types 26, 53,
      66) and low-risk (types 6, 11, 40, 42, 43, 44, 54, etc) types according to their
      oncogenic potential. HPV is currently considered as the main aetiological factor
      of cervical intraepithelial neoplasia and cervical cancer. HPV types classified
      in Papillomaviridae family, are non-enveloped, icosahedral symmetric viruses
      about 55 nm in size. Viral genome consists of circular double-stranded DNA, about
      8 kb in size, encodes for early proteins (E1, E2, E4, E5, E6, E7) which play role
      in virus replication and cell transformation, and for late (L1, L2) proteins
      which are the structural units of the viral capsid. Integration of HPV DNA into
      the host chromosome is crucial for viral persistence and for carcinogenic
      effects. Viral DNA may integrate randomly to the cell genome and integration can
      lead to the deregulation and increase of E6/E7 expression leading to oncogenesis.
      However, increased expression of E6/E7 gene products may occur without genome
      integration. E6 and E7 proteins of especially highrisk HPV types (e.g. types 16
      and 18) interact with tumor supressor proteins such as p53 and retinoblastoma
      (pRb) proteins, respectively; inhibit their functions and cause uncontrolled
      proliferation and immortalization of the cells. The binding of E6 protein to p53
      leads its rapid degradation, and the eclipse in the G1 phase, DNA repair
      mechanisms and apoptosis are terminated. In the other way, E7 protein interacts
      with pRb and mitotically interactive cellular proteins such as cyclin-E, causing
      stimulation of cellular DNA synthesis and cell proliferation. Recently identified
      genes E3 and E8 are located in early gene region and found only in a few
      papillomavirus types (HPV 1, 11, 16, 31, 33). A fusion protein, E8^E2C, functions
      as a negative regulator for HPV DNA replication and it is thought that this
      protein may play a role in the control of viral copy number as well as in the
      stable maintenance of HPV episomes. In this review article, the genomic structure
      of HPV and the functions of gene products have been summarized.

PMID- 22951666
TI  - [Linezolid-resistant Enterococcus faecium: the first G2576T mutation in Turkey].
AB  - Linezolid which is the first member of oxazolidinone class of synthetic
      antimicrobial agents, was licensed for the treatment of gram-positive coccal
      infections in Turkey in 2006. In recent years, multidrug-resistant pathogens,
      especially vancomycin-resistant enterococci (VRE), have emerged rapidly worldwide
      and linezolid exhibited good clinical efficacy against VRE. However, linezolid
      resistant bacteria have been reported from Turkey. In April 2011, a 66-year-old
      paraplegic woman was admitted to our hospital because of an infected decubitis
      ulcer and empirical antibiotic therapy was started. Since the patient's condition
      worsened during treatment, she was moved to the intensive care unit. Klebsiella
      pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      Enterococcus faecium were recovered from tracheal aspirates and blood,
      respectively. Following three weeks of linezolid therapy blood culture yielded
      linezolid and vancomycin resistant E.faecium. Linezolid resistance in the VRE
      strain was confirmed by polymerase chain reaction and sequence analysis,
      subsequently. Linezolid-resistant two isolates were identified as E.faecium by
      16S rRNA sequencing and both isolates had G2576U mutation in 23S rRNA gene.
      Linezolid resistance which was identified in a vancomycin-resistant E.faecium
      isolate is a new problem for Turkey. Last year another mutation related to
      linezolid resistance was reported from Istanbul, Turkey. The isolate had G2576T
      mutated 23S rRNA genes. Resistance should be considered and closely followed-up
      during linezolid treatment.

PMID- 22951667
TI  - [Can mannose-binding lectin and plasma level of soluble urokinase receptor be
      used in diagnosis and treatment monitorization of brucellosis patients?].
AB  - The aim of this study was to evaluate the diagnostic value of serum mannose
      binding lectin (MBL) and plasma soluble urokinase plasminogen activator receptor
      (SuPAR) levels in monitoring the treatment in patients with brucellosis, by
      comparing their levels before and after treatment with the values obtained from
      healthy control group. Thirty brucellosis patients (mean age: 25.8 +/- 12.2
      years; 15 were male) and 28 healthy controls (mean age: 29.3 +/- 12.3 years; 15
      were male) were included in the study. Patients were diagnosed with brucellosis
      according to the characteristic clinical findings and by brucella standard tube
      agglutination test (SAT) titer >= 1/160 and/or blood culture positivity. Serum
      MBL (Antibodyshop, Denmark) and plasma SuPAR (Virogates, Denmark) levels were
      investigated with commercial ELISA kits. In our study, no statistical
      significance was observed between the pre-treatment (13.8 +/- 13.4 ng/ml) and
      post-treatment (12.4 +/- 13.1 ng/ml) MBL levels of the patient group and MBL
      levels of the control group (16.5 +/- 14.8 ng/ml) (p> 0.05). Moreover, the mean
      SuPAR levels measured in pre-treatment and post-treatment plasma samples of the
      brucellosis patients was 5.1 +/- 1.9 ng/ml and 2.9 +/- 1.3 ng/ml, respectively,
      while the mean SuPAR level was 1.8 +/- 0.5 ng/ml in the control group. The
      difference between mean SuPAR levels of patients in pre- and post-treatment
      samples was found statistically significant (p< 0.001). In addition SuPAR levels
      were significantly higher in patients before and after treatment than the control
      group (p> 0.001). In conclusion, plasma SuPAR level would be a useful marker for
      the diagnosis and treatment follow up of the patients with brucellosis.

PMID- 22951668
TI  - Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene
      amplification is a negative prognostic factor in early breast cancer.
AB  - BACKGROUND: Human epidermal growth factor receptor (HER)-2 testing in patients
      with operable breast cancer is aimed at identifying candidates for adjuvant anti
      HER-2 treatment. However, commonly defined "HER-2(-)" tumors express variable
      levels of the HER-2 protein, which can influence prognosis. We compared the
      clinical outcomes of operable breast cancer patients stratified according to a
      common HER-2 testing algorithm. METHODS: We studied 1,150 women (median age, 58
      years; range, 22-94 years) undergoing surgery for early breast cancer at our
      institution. HER-2 status was determined using the HercepTestTM (Dako, Glostrup,
      Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients
      receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the
      disease-free survival (DFS) time was studied using multivariate Cox proportional
      regression analysis. RESULTS: Four hundred-fifty seven (40%), 454 (39%), 116
      (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2(
      ) by FISH, and HER-2(+) (3+ or HER-2(+) by FISH), respectively. Compared with a
      HER-2 0 or 1+ status, a HER-2 2+/HER-2(-) by FISH status was associated with a
      worse DFS outcome on multivariate analysis. Compared with a HER-2(+) status, a
      HER-2 2+/HER-2(-) status showed a time-dependent effect on the DFS probability,
      with an initial advantage that worsened every year by a factor of 1.649.
      CONCLUSION: A HER-2 2+/HER-2(-) status is an adverse prognostic factor in
      patients with operable breast cancer. Because of suggestions from randomized
      trials that the benefits of adjuvant trastuzumab may not be limited to patients
      with HER-2(+) tumors, patients with a HER-2 2+/HER-2(-) status are ideal
      candidates for studies testing this hypothesis.

PMID- 22951669
TI  - Erythema multiforme and Malarone((r)).

PMID- 22951670
TI  - Derivation and clinical validation of consistency indices on the test of memory
      malingering.
AB  - Response consistency (CNS) is considered in free-standing performance validity
      measures like the Medical Symptom Validity Test (MSVT). This study examined the
      utility of CNS scores on the Test of Memory Malingering (TOMM). CNS indices were
      derived in a non-clinical undergraduate sample randomized to control (n = 73),
      naive simulator (n = 73), and coached simulator (n = 73) groups. Two of the three
      TOMM CNS measures showed higher classification rates identifying naive simulators
      than the standard TOMM criteria; CNS measures classified coached simulators
      better than the standard TOMM criteria. Coached simulators outperformed naive
      simulators on the standard TOMM scores, but not on CNS measures, suggesting their
      resilience to coaching. In a separate clinical sample of veterans (N = 92), TOMM
      CNS scores exhibited comparable classification rates with the standard TOMM
      scoring using the MSVT as the performance validity criterion. Overall, findings
      support TOMM CNS scores, especially in settings in which examinee coaching is
      likely.

PMID- 22951671
TI  - Validation of the route map recall test for getting lost behavior in Alzheimer's
      disease patients.
AB  - Getting lost (GL) behavior is among the early symptoms in Alzheimer's disease
      (AD). Only a few tests, however, have been developed to screen for this symptom.
      The aim of this study was to develop an instrument, the Route Map Recall Test
      (RMRT), for the screening of the GL problem in AD patients. We examined the
      psychometric properties of the RMRT and its clinical utility to predict the GL
      risk in 23 AD patients and 43 cognitively healthy older adults. The results
      showed that the RMRT has a sound reliability (test-retest, r = .752, p < .001;
      Cronbach's alpha = 0.887, p < .001). The convergent validity was supported by the
      high correlations with Trail Making Test A and B. With the optimal criteria
      (93.5/104), the discriminative validity for the diagnosis of AD showed good
      sensitivity (86%) and specificity (70%), and sensitivity (100%) and specificity
      (67%) for GL in AD patients. The findings support the RMRT to be a useful tool
      for clinical screening of AD patients and their GL risk.

PMID- 22951673
TI  - First tellurium-containing phthalocyanine analogues: strong effect of tellurium
      on spectral, redox and conductivity properties of porphyrazines with annulated
      chalcogenodiazole ring(s).
AB  - The first tellurium-containing phthalocyanine analogues have been prepared and
      spectroscopically characterised: the Mg(II) complex of tetra(1,2,5
      telluradiazolo)porphyrazine and a low-symmetry tert-butyl substituted Mg(II)
      tribenzoporphyrazine with one fused 1,2,5-telluradiazole ring. It was observed
      that the introduction of Te atom(s) reduces the energy of the Q-transition,
      facilitates the reduction of the macrocycle and strongly increases the
      conductivity of thin films.

PMID- 22951674
TI  - [The use of multimedia technologies in otorhinolaryngology].
AB  - The possibilities of using computer-assisted technologies in otorhinolaryngology
      have been analysed with a view to enhancing the efficacy of the teaching activity
      and improving the quality of diagnostics and treatment of various ENT diseases.
      It is emphasized that computers may be used not only to reproduce traditional
      teaching modalities but also to supplement them with new approaches inaccessible
      with conventional methods; the introduction of these approaches is of special
      importance for medical universities and institutes. The use of computer-based
      technologies in otorhinolaryngological practice made it possible to significantly
      improve the quality of diagnostics and treatment of the most widespread ENT
      diseases. For all that, however, the potential of computer technologies in
      otorhinolaryngology is by no means exhausted.

PMID- 22951675
TI  - [The influence of chronic otitis media on the sensorineural component of
      hearing].
AB  - The objective of the present study was to estimate the influence of chronic
      suppurative otitis media (CSOM) on the sensorineural component of deafness in the
      patients presenting with unilateral otitis media. A total of 49 patients with
      this pathology were included in the study. The bone conduction thresholds at the
      affected side were measured at a frequency of 500, 1000, 2000, and 4000 Hz and
      compared with those in the unaffected ear. The loss of hearing was especially
      well-apparent in the examination at higher frequencies and significantly
      deteriorated with age. The study did not reveal a marked influence of duration of
      the disease on the development of the sensorineural component of deafness.

PMID- 22951676
TI  - [Methods for the investigations into the functional state of the organ of hearing
      and equilibration in locomotive drivers for the early diagnostics of occupational
      sensorinerual deafness].
AB  - AIM OF THE STUDY: to estimate the diagnostic value of various tests for the
      expert assessment of the functional state of the organ of hearing and
      equilibration in locomotive drivers employed by the Minsk branch of the
      Belorussian railway. MATERIALS AND METHODS: A total of 224 members of the
      locomotive teams were examined. Healthy men (n=56) served as controls. Tonal
      threshold audimetry (TTA), molecular-genetic study. The study has demonstrated
      the advantages of performing wide-range TTA in conjunction with dynamic
      stabilometry. The molecular-genetic studies for the detection of potential 35delG
      mutations proved to be of little diagnostic value.

PMID- 22951677
TI  - [The algorithms for the tuning of the speech processors of cochlear implants].
AB  - The tuning of the speech processors of cochlear implants implies the measurement
      of the threshold perception levels and the achievement of the maximally
      comfortable level of loudness in each auditory channel. The authors present a
      detailed description of the approach to the optimal tuning including the sequence
      of procedures and manipulations for this purpose, from the first tuning to the
      achievement of the desired result. This algorithm summarizes the worldwide and
      the authors' own experience based on the original investigations that have been
      carried in the Sankt-Peterburg Research Institute of Otorhinolaryngology and
      Speech during more than 15 years.

PMID- 22951678
TI  - [The clinical study of tympanic membrane mobility with the use of the autodyne
      technique].
AB  - AIM OF THE STUDY: to estimate the possibility of application of the autodyne
      method for the detection of nano-displacements of the tympanic membrane and
      diagnostics of ear diseases. METHODS: nano-displacements of the tympanic membrane
      were revealed with the use of the original laser-assisted autodyne technique for
      the measurement of nano-vibrations. The majority of the measurements were
      performed in the free auditory field. A total of 182 patients allocated to 7
      groups depending on the form of hearing disturbances or their absence were
      involved in the study. RESULTS: the values of nano-displacement of the tympanic
      membrane at different levels of acoustic pressure have been obtained for
      otologically healthy individuals. The age dependence of this parameter was
      investigated in the absence of otological pathology. Similar studies were carried
      out in different groups of patients with the diseases of the middle and internal
      ears. The mobility of the tympanic membrane was shown to be significantly altered
      in the presence of adhesive events in the middle ear and pathological changes in
      the Eustachian tube. The possibilities of the clinical application of the
      proposed method have been estimated.

PMID- 22951679
TI  - [Specific surgical features of the tympanic cavity in the children under the age
      of 3 years].
AB  - The objective of the present study was to obtain new data of practical
      significance from the comparative analysis of the anatomical structure of the
      tympanic cavity in newborn infants and young children. MATERIALS AND METHODS: A
      total of 23 and 24 temporal bone macropreparations obtained from the newborn
      infants and young children (between 1 to 3 years of age) respectively were
      available for the examination that included sequential dissection, measurement,
      and macrophotographing of the specimens. RESULTS: The study has revealed a number
      of distinctive features of the anatomical structure of the tympanic cavity in
      newborn infants and young children.

PMID- 22951680
TI  - [Epidemiological aspects of congenital stridor].
AB  - The objective of the present work was to study epidemiology of congenital stridor
      as a leading symptom of laryngeal malformation. The continuous sampling method
      was employed to perform the retrospective analysis of the growth charts of the
      patients attending three children's polyclinics in Moscow (9.625 patients born
      between 2005 and 2009). In addition, the medical histories of 4.623 newborn and
      breast-fed babies under the age of 1 year admitted to the Department of Newborn
      and Neonatal Pathology, Saint Vladimir City Children's Clinical Hospital, and 347
      patients of the Department of Reconstructive Laryngeal Surgery were analysed. The
      children with the history of tracheal intubation in the preceding period were
      excluded from the study. The frequency of congenital stridor annually diagnosed
      in the aforementioned polyclinics varied from 0.17 to 5.8% compared with 1.5% in
      the general population. It was 2.21 to 3.14% (mean 2.47%) among the children
      treated at the Clinical Hospital. In the children under the age of 1 year,
      congenital malformations accounted for 90.8% of all laryngeal diseases. The
      principal cause of stridor was shown to be laryngomalacia. This pathology was
      diagnosed in 91.9% of the cases included in this study. In 11.2% of the patients,
      this condition occurred in combination with other congenital pathologies. It is
      concluded that the diagnosis of congenital stridor is an indication for laryngeal
      endoscopy regardless of the children's age starting from the first day of life.
      Meeting this recommendation allows the cause of stridor to be established and the
      treatment strategy to be developed on an individual basis.

PMID- 22951681
TI  - [The influence of the defects and deformities in the intranasal septum on the
      main functions of the nose (preliminary report)].
AB  - AIM OF THE STUDY: to estimate the influence of the defects and deformities in the
      intranasal septum on the main functions of the nose and therefore on the state of
      the upper respiratory tract and the ears. METHODS: A total of 180 patients
      suffering deformation of the nasal septum were available for the examination. The
      study included the evaluation of breath characteristics, excretory and
      inspiratory functions of the nose compared with control with the use of the
      conventional methods including rhinometry. RESULTS: The patients presenting with
      the defects and deformities in the intranasal septum were found to have nasal
      breathing problems, impaired sense of smell, disturbances of the excretory,
      inspiratory, air-transporting, and air-heating functions of the nose. Comparative
      analysis of laryngeal, pharyngeal, tracheal, bronchial, and pulmonary disorders
      has demonstrated the significant differences in the frequency and duration of
      these diseases and in the efficacy of their treatment between the patients of the
      study and control groups. It is concluded that the early recovery of nasal
      functions, in the first place the respiratory one, is an important precondition
      for the efficacious prevention of various catarrhal and other laryngeal diseases
      of the larynx, pharynx, trachea, bronchi, lungs, and ears.

PMID- 22951682
TI  - [The use of laser Doppler flowmetry for the estimation of the influence of
      intranasal medications on microcirculation in nasal cavity mucosa].
AB  - AIM OF THE STUDY: to investigate the influence of various intranasal medications
      on the microcirculatory bed in nasal cavity mucosa using the original method of
      laser Doppler flowmetry. METHODS: this comprehensive study of the influence of
      intranasal medicines on nasal cavity mucosa using laser Doppler flowmetry was
      designed to evaluate the mucociliary clearance, breathing efficiency of the nose,
      and subjective symptoms of its impairment. The outcomes of a single application
      of intranasal medications were estimated in 90 rhinologically healthy subjects;
      in 15 of them, the micrcirculatory blood flow in the nasal cavity was
      investigated in the early postoperative period with the use of intranasal
      decongestants and irrigation products. RESULTS: this study has demonstrated the
      relationship between the changes in the microcirculatory bed and the application
      of intranasal medications acting on nasal mucosa. Moreover, these agents were
      shown to affect intranasal mucosa and its microcirculatory bed following
      rhinological surgical interventions. Tachyphylaxis of the microcirculatory bed
      after the administration of the decongestants developed earlier than previously
      thought. At the came time, irrigation therapy exerted the beneficial effect on
      the state of the intranasal microcirculatory bed in the postoperative period.

PMID- 22951683
TI  - [Optimization of the surgical methods for the treatment of recurrent nasal
      bleeding (a pathologo-anatomical study)].
AB  - The objective of the present work was to study specific features of blood supply
      to the nasal cavity by staining mandibular and ethmoidal arteries to reveal their
      size and topographic features under conditions of a pathologo-anatomical
      department. The secondary objective was to modify the existing and develop new
      methods for the ligation of these vessels. This pathologo-anatomical study was
      based on 16 preparations examined with the use of up-to-date optical facilities.
      The results of investigations of the topographo-anatomical peculiarities of blood
      supply in the nasal cavity are supplemented by the evaluation of the potential of
      endoscopic rhinosurgery for the treatment of recurrent nasal hemorrhage. The
      methods for endoscopic ligation of mandibular and ethmoidal arteries have been
      developed and optimized.

PMID- 22951684
TI  - [Peculiar manifestations of familial chlamydiasis of the upper respiratory
      tract].
AB  - The aim of the present study was to elucidate the frequency of chlamydial
      infection in the members of the families having the confirmed disease and
      concomitant ENT pathologies. Another objective was the comparative analysis of
      otorhinolaryngological morbidity in the families with and without the carriers of
      respiratory chlamydiasis. A total of 87 families were involved in the study.
      Chlamydial infection was diagnosed by a set of laboratory methods including
      direct immunofluoresent and immunoenzyme analysis as well as polymerase chain
      reaction (PVR). It was shown that the presence of a patient suffering from
      respiratory chlamydiasis in the family creates the risk of infection for its
      remaining members. Moreover the frequency of ENT morbidity increases in the
      families that serve as a hotbed of chlamydiasis of the upper respiratory tract.

PMID- 22951685
TI  - [The application of a CO(2)-laser for tonsillectomy in the patients presenting
      with chronic decompensated tonsillitis as an alternative to the traditional
      methods of surgical treatment].
AB  - AIM OF THE STUDY: to estimate the clinical efficiency and advantages of the
      surgical treatment of palatal tonsils with the use of a CO(2)-laser in comparison
      with the traditional methods of tonsillectomy. METHODS: A total of 175 patients
      presenting with decompensated tonsillitis were available for the observation of
      which 79 were operated with the use of a CO(2)-laser. The control group was
      comprised of the patients undergoing conventional tonsillectomy. RESULTS: The
      study confirmed the high clinical efficiency of the ablation of palatal tonsils
      using the CO(2)-laser and its advantages in terms of reduced duration of the
      postoperative period, requirements for analgesic and antibacterial medications,
      recovery of the swallowing function and speech.

PMID- 22951686
TI  - [Ultrasonic therapy of vasomotor rhinitis in combination with the application of
      topical corticosteroids].
AB  - The objective of this work was to study the feasibility and effectiveness of the
      cavitational low-frequency ultrasound treatment of vasomotor rhinitis in
      combination with the application of topical corticosteroids. The study included
      220 patients with the confirmed neurovegetative form of vasomotor rhinitis
      treated with the use of a Kavitar apparatus for the ultrasonic cavitational jet
      lavage. The data obtained indicate that the low-frequency cavitational treatment
      of intranasal mucosa in combination with the application of topical
      corticosteroids may be recommended as an efficatious method for the treatment of
      vasomotor rhinitis.

PMID- 22951687
TI  - [The application of biopolymer-based antiseptic drugs for the surgical treatment
      of intranasal and paranasal tumours].
AB  - The authors report their experience with the application of the local antiseptic
      preparation Ambipor for the treatment of operative wound infection in the
      patients presenting with malignant neoplasms. Ambipor was used in 23 patients
      receiving surgical treatment of locally advanced intranasal and paranasal
      tumours. It was shown that the application of ambipor allows decreasing the risk
      of development of wound infection in the postoperative period.

PMID- 22951688
TI  - [Cryoradiation therapy of the patients presenting with locally advanced auricular
      skin cancer].
AB  - The objective of the present work was to improve the efficacy of treatment of
      locally advanced auricular skin cancer with the use of the newly proposed
      combined method including cryogenic and radiotherapy. The choice of the optimal
      temporal and thermal parameters of combined cryoradiotherapy was based on the
      results of previous experimental and theoretical investigations. Each radiation
      treatment session was immediately preceded by local cooling of the tumour down to
      0 degrees C - minus 5 degrees C with a nitrogen vapour. Radiotherapy was
      performed with the use of either photon or electron radiation at a single local
      dose of 2 Gy-2.25 Gy (the total cumulative dose 64 Gy-68 Gy). As many as 14
      patients presenting with locally advanced auricular skin cancer received combined
      cryogenic and radiotherapy; 10 of them had basal cell carcinoma and 4 squamous
      cell carcinoma. In all these cases, the treatment resulted in the complete
      regression of the tumours. Further observation during a follow-up period from 2
      to 14 years in duration demonstrated that only two patients developed tumour
      relapses. These secondary neoplasms were successfully treated by cryodestruction
      (n=1) and surgical ablation (n=1). The proposed cryoradiotherapy made it possible
      to preserve the anatomical relief of the auricle and the auditory passage with
      good aesthetic and functional outcomes.

PMID- 22951689
TI  - [Diagnostics of keratitis-ichthyosis-deafness syndrome (KID- syndrome)].
AB  - The combination of pre-lingual and sensorinerual deafness with skin
      hyperkeratinization is a relatively rare pathology. Only 11 families affected by
      this disorder were described in the literature during the last 30 years (from
      1975 to 2002). To date, there are no more than 50 cases of this condition known
      in the world. Modern molecular methods revealed in all such patients a mutation
      in the GJB2 gene as the primary cause of the disease. We studied a 4 year-old
      girl with bilateral congenital grade IV sensorineural deafness. Her unusual
      appearance drew attention aas early as the primary examination; the patient had
      the deep-set eyes and dry skin over the entire body, she presented with
      hypotrichosis of the scalp, thin and light-blond hair. Analysis of the nucleotide
      sequence of the GJB2 gene revealed the substitution of guanine-148 by adenine
      that led to D50N amino acid substitution. This dominant mutation proved to be the
      cause of keratitis-ichthyosis-deafness syndrome (KID-syndrome). A review of the
      literature concerning molecular diagnostics and clinical features of this
      syndrome is presented. The results of molecular-genetic investigations provided
      the data on pathogenesis of different variants of sensorineural deafness and the
      associated genotype-phenotype relationships that may be used as a basis for the
      further development of the methods for the prevention and treatment of KID
      syndrome.

PMID- 22951690
TI  - [Criteria for the objective assessment of the dynamic state of the retraction
      pockets in the children presenting with excudative otitis media].
AB  - This publication continues the preceding paper entitled "Early diagnostics of the
      retraction pockets in the tympanic membrane of the children". The objective of
      the present work was to develop the criteria for the objective estimation of the
      dynamic state of the retraction pockets (RP) in the children at different stages
      of excudative otitis media. The secondary objective was to develop an approach to
      the early diagnostics of cholesteatoma of the middle ear. A group of 138 children
      at the age varying from 1 to 17 years was placed under dynamic observation for
      the purpose of drawing up the individual "photo-roentgenological passport of the
      retraction pockets". Special attention was given to RP-semiotics of different
      forms of the syndrome and its severity in accordance with the classification
      universally accepted by foreign researchers. The results of the dynamic
      observations were used to develop the indications for the early preserving
      surgical treatment. It was given to 16 children six of which presented with
      cholesteatoma. The original illustrative materials for all variants of the
      retraction pockets are presented.

PMID- 22951691
TI  - [A new method for the fixation of sound-conducting elements of the middle ear
      during ossiculoplasty].
AB  - The objective of the present work was to estimate the possibilities of the
      application of platelet-enriched plasma as a filtering material for
      ossiculoplasty. The results of surgical interventions on 120 patients presenting
      with chronic suppurative otitis media are reported. All the patients underwent
      closed-type sanation surgery (differential atticoanthrotomy) including either
      complete or partial restoration of the sound conduction mechanism in the middle
      ear. Platelet-enriched plasma was applied into the tympanic cavity of 55 patients
      as a fixing material for the reconstruction of the chain of the auditory
      ossicles. Ossiculoplasty without additional fixation was performed in 65 patients
      comprising the control group. The results of the study indicate that a clot of
      platelet-enriched plasma may be a good fixing material for the reconstruction of
      the entire chain of auditory ossicles and can be used for all types of
      ossiculopasty.

PMID- 22951692
TI  - [The aerodynamic and hydrodynamic techniques for the removal of bacterial films
      and clots from the middle ear].
AB  - This study was designed to estimate the efficacy of aerodynamic and hydrodynamic
      techniques for diagnostics and treatment of otitis interna and otitis media and
      for the evacuation of bacterial films and clots from the cavities and canals of
      the middle ear. These methods were realized with the use of an otobarohydroscope
      and otobarohydroendoscope. The data obtained confirm that both the aerodynamic
      and the hydrodynamic techniques provide an efficacious tool for the destruction
      of bacterial films and clots and their evacuation from the cavities and canals of
      the middle ear.

PMID- 22951693
TI  - [Local therapy of acute sensorinerual deafness by means of intratympanic
      administration of steroids].
AB  - AIM OF THE STUDY: to estimate the efficacy of local therapy of acute
      sensorinerual deafness by means of intratympanic administration of steroids.
      PATIENTS AND METHODS: the study included 73 patients presenting with acute
      sensorinerual deafness (ACND). 24 of them were given local steroid therapy
      (through a shunt) during 6 months, another 24 patients received traditional
      systemic therapy, and 25 ones systemic steroid monotherapy (intravenously) for 10
      days. The tonal threshold audiograms obtained before as well as 1, 3, and 6
      months after the treatment were compared. It was shown that the efficacy of the
      intratympanic administration of steroids during 1 month was not significantly
      different from that of systemic therapy. The long-term therapy (for 6 months) by
      the intratympanic administration of steroids yielded better results than systemic
      therapy. CONCLUSION: the local intratympanic administration of steroids may be
      used as a self-contained method for the primary treatment of acute sensorinerual
      deafness.

PMID- 22951694
TI  - [The cytokine status as a criterion for the efficacy of intranasal aerosol
      therapy with the use of a cycloferon solution in the patients presenting with
      allergic rhinosinusitis].
AB  - The objective of the present study was to estimate the informative value of the
      variations in the levels of the principal cytokines for the evaluation of the
      efficacy of local immunotherapy in the immunocompromised individuals presenting
      with allergic rhinosinusitis (ARS). The study was focused on the analysis of the
      outcomes of the treatment with the use of a new highly effective therapeutic
      modality based on the intranasal administration of a cycloferon aerosol solution
      (125 mg/ml) used in allergologic practice. The main criterion for the efficacy of
      this treatment was variations of IL-4, IL-8, TNF-alpha, and interferon-gamma
      levels. The method for the measurement of concentrations of the principal
      cytokines may be recommended for the evaluation of the efficacy and prognosis of
      the treatment of allergic rhinosinusitis.

PMID- 22951695
TI  - [Intoxication syndrome concomitant with recurrent streptococcal tonsillitis and
      its correction].
AB  - The objective of the present work was to study selected features of intoxication
      in the patients presenting with recurrent tonsillitis (RT) and managed by means
      of the combination of basal therapy with reamberine, a preparation showing the
      detoxication activity. A total of 70 patients with moderately severe recurrent
      streptococcal tonsillitis induced by infection with group A beta-hemolytic
      streptococci were available for the examination. Characteristics of endogenous
      intoxication were explored. The study has demonstrated that recurrent tonsillitis
      is associated with the development of the pronounced symptoms of endogenous
      intoxication (EI) as suggested by the enhanced leukocytic index of intoxication
      (LII) and the elevated levels of medium molecular weight molecules (MWM) with the
      simultaneous impairment of detoxication properties of albumin. Collectively,
      these changes are indicative of incompleteness of the pathological process that
      may be regarded as an unfavourable prognostic factor and suggests the risk of
      development of tonsillogenic pathology, its relapses, and chronization of the
      process. Taken together, these findings indicate the necessity of developing
      novel approaches to the treatment of recurrent tonsillitis with special reference
      to the use of pharmaceutical products possessed of detoxication activity.
      Reamberine introduced in the combined treatment of RT was shown to decrease the
      severity of intoxication as confirmed by normalization of LII and MWM levels as
      well as the improvement of detoxication properties of albumin. It is concluded
      that therapeutic efficacy of reamberine opens up wide prospects for its clinical
      applications.

PMID- 22951696
TI  - [The efficacy of rinopront for the treatment of acute and chronic rhinitis in the
      children].
AB  - The objective of the present study was to estimate the therapeutic efficacy of
      rinopront used to treat inflammatory diseases of the nasopharynx in the children.
      The study included 32 patients at the age between 12 and 14 years presenting with
      various forms of acute and chronic rhinitis. The children with infectious
      inflammatory rhinitis with concomitant catarrhal maxillary sinusitis and
      pronounced symptoms of rhino-conjunctival syndrome recovered within 4-5 days
      after the initiation of rhinopront therapy. The patients presenting with
      vasomotor and all-the-year-round allergic rhinitis needed two courses of
      treatment (5 days each) to recover. The duration of treatment of mild seasonal
      rhinitis was 4 days whereas the moderately severe disease required the second 5
      day course of therapy to be performed to arrest the disease activity.

PMID- 22951697
TI  - [Local antibacterial therapy for the inflammatory diseases of the external and
      middle ear].
AB  - The objective of the present study was to estimate the efficacy and safety of
      candibioic designed for the treatment of the patients presenting with diffuse
      otitis externa and chronic otitis media. The open randomized trial included 40
      patients with diffuse otitis externa and 40 ones with chronic otitis media who
      had undergone a surgical sanitation procedure. Their standard clinical and
      otorhinolaryngological examination was supplemented by the characteristic of
      clinical symptoms and personal complaints using the 10-score scale. The composite
      preparation candibiotic was found to be equally effective for the treatment of
      both diffuse otitis externa and chronic otitis media. The results of the study
      give reason to recommend the use of candibiotic as an efficacious and safe drug
      for the treatment of these conditions.

PMID- 22951698
TI  - [A rare case of malignant laryngeal shcwannoma].

PMID- 22951699
TI  - [The giant fungal body in the sphenoidal sinus and the destruction of the skull
      base].
AB  - The objective of the present study was to estimate the efficacy of the optical
      systems with the variable visual field angle applied for the endoscopic
      interventions on the paranasal sinuses. The authors report a clinical observation
      of the patient presenting with the giant fungal body in the sphenoidal sinus
      responsible for the partial destruction of the bone canal of the optic nerve and
      the internal carotid artery. The patient was treated by endoscopic shenoidotomy
      through the paraseptal approach with the use of a sinuscope with the variable
      visual field angle. It was shown that the use of optical devices with the
      variable visual field angle makes it possible to significantly reduce the
      duration of the surgical intervention, facilitates orientation in the difficult
      of-access regions , and ensures adequate control during the removal of neoplasms
      at the basis of the skull.

PMID- 22951700
TI  - Paediatric cardiologist is accused of making sexual advances to young boys in
      Paris and Kenya.

PMID- 22951701
TI  - Concerns raised over organ donation "matching" website.

PMID- 22951702
TI  - Jeremy Hunt succeeds Andrew Lansley as health secretary.

PMID- 22951703
TI  - Sodium amobarbital: historical perspectives and neurorehabilitation clinical
      caveats.
AB  - The sodium amobarbital (amytal) (SA) interview is a technique that has been
      utilized in the treatment of a variety of disorders since its introduction in
      1929. Since that time, there has been an assortment of research conducted showing
      its value in both differential diagnosis and treatment of multiple conditions.
      Notwithstanding the substantive amount of experience with the technique and its
      application to a myriad number of clinical conditions, it remains a seldom used
      procedure in clinical practice and certainly in neurorehabilitation. This paper
      will review the history of SA, as well as summarize the literature published over
      the past two decades on the clinical applications of SA to provide readers with a
      foundation for the utility of this agent, as well as the sodium amytal interview
      (SAI) in neurorehabilitation clinical practice. Special emphasis will be placed
      on the use of the SAI in individuals with functional disorders that may be seen
      in the neurorehabilitation setting, as well as various classes of pain disorders.

PMID- 22951704
TI  - A systematic review of the effects of occupational therapy for persons with
      dementia: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Meta-analysis was conducted to examine effects of OT interventions
      based on sensory stimulation, environmental modification and functional task
      activity on the behavioral problems and depression of individual with dementia.
      SEARCH STRATEGY: An extensive search in database such as MEDLINE, CINAHL,
      ProQuest Medical Library, and Cochrane and OT related 11 journals was performed.
      SELECTION CRITERIA: Potential studies were identified through the KEYWORDS:
      dementia or Alzheimer, randomized controlled trials and occupational therapy or
      occupational therapist or ADL or sensory stimulation or Snoezelen or
      environmental modification or education for caregivers. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently identified studies, extracted data,
      assessed methodological quality of the studies. Effect size was estimated using
      standardized mean difference with 95% confidence intervals. Significant
      heterogeneity and publication bias were investigated. MAIN RESULTS: Nine studies
      including 751 people were selected. Sensory stimulation was effective
      intervention in improving behavioral problems (0.32; 95% CI, 0.04 to 0.59).
      CONCLUSION: This review identified that OT intervention based on sensory
      stimulation was effective intervention to improve behavioral problems. However,
      the number of studies included in this review is limited. More research is needed
      to enable evidence-based OT for dementia patients.

PMID- 22951705
TI  - Botulinum toxin use in neuro-rehabilitation to treat obstetrical plexus palsy and
      sialorrhea following neurological diseases: a review.
AB  - In neuro-rehabilitation, botulinum toxin (BTX) as adjunct to other interventions
      can result in a useful therapeutic tool treating disabled people. Other than
      spasticity, numerous motor and non motor disorders can complicate clinical course
      and hamper rehabilitative process of neurological impaired patients. A review of
      BTX use in treating muscular imbalance of children with obstetrical brachial
      plexus palsy and in reducing sialorrhea following neurological diseases including
      amyotrophic lateral sclerosis (ASL), Parkinson disease and cerebral palsy (CP) is
      provided. Clinicians have to face unique and difficult to treat clinical
      conditions such as ulcers, sores and abnormal posture and movement disorders due
      to neurological affections. BTX effectiveness in treating some of these
      conditions is also provided. Since, neurologically disabled subjects can show
      complex dysfunction, prior to initiating BTX therapy, specific functional
      limitations, goals and expected outcomes of treatment should be evaluated and
      discussed with family and caregivers.

PMID- 22951706
TI  - Delayed neural degeneration following gamma knife radiosurgery in a patient with
      an arteriovenous malformation: a diffusion tensor imaging study.
AB  - Gamma knife surgery (GKS) is a proven modality for the treatment of arteriovenous
      malformations (AVMs), but neural degeneration is a serious complication of GKS.
      In this study, we report on a patient who displayed delayed neural degeneration
      following GKR, using diffusion tensor imaging (DTI). A 43-year-old male patient
      was diagnosed with an intraventricular hemorrhage (IVH) due to rupture of an AVM
      in the right middle cerebellar peduncle, and exhibited cognitive impairment,
      quadriparesis, and ataxia after IVH onset. He underwent GKS 5 weeks after onset.
      Brain MRIs performed at 6 weeks, 7 months, and 21 months post-onset revealed
      encephalomalactic lesions in the right pons, middle cerebellar peduncle, and
      medulla oblongata. DTI at 6 weeks post-onset suggested neural injuries of the
      right corticospinal tract (CST), right middle cerebellar peduncle (MCP), and
      right inferior cerebellar peduncle (ICP). DTI at 7 months suggested that the
      right CST and right ICP had recovered to some extent, which concurred with
      improved clinical manifestations. However, at 21 months, four neural tracts
      (right CST, right MCP, and both ICPs) appeared to have degenerated, which was in
      line with aggravation of corresponding clinical manifestations. Experiences of
      this patient suggest DTI is a useful technique for the detection of neural
      degeneration after GKS.

PMID- 22951707
TI  - Adverse effects of motor-related symptoms on the ipsilateral upper limb according
      to long-term cane usage.
AB  - OBJECTIVE: Although the cane is prescribed to aid in daily living and social
      participation in stroke patients, this study aimed to identify whether long-term
      cane usage affected sensorimotor functions in the distal part of the non-affected
      upper limb in relation to a tracking task, a nine-hole pegboard test, and
      proprioceptive joint sense. PATIENT AND METHOD: Forty stroke patients who were
      divided into a cane using group (CUG) or a non-cane using group (NCUG)
      participated in this study. Subjects were evaluated in a tracking task for
      visuomotor coordination, a nine-hole pegboard test for dexterous hand motion, and
      a joint reposition test for proprioceptive sense integrity. RESULT: Comparison of
      the CUG and NCUG revealed significant differences in performance of the tracking
      task, the nine-hole pegboard test, and the joint reposition test (p < 0.05). The
      CUG had more difficulty performing visuomotor coordination and dexterous hand
      motion tasks compared with the NCUG. Proprioceptive joint sense was also
      deteriorated in the CUG. CONCLUSION: These results suggest that stroke patients
      who use a cane for a long period, could experience decreased sensorimotor
      function in the ipsilateral upper limb of a damaged hemisphere. Therefore, it
      will be necessary to provide careful evaluation and appropriate therapeutic
      intervention for stroke patients who require the use of a cane over a long
      period.

PMID- 22951708
TI  - Neural connection between injured cingulum and pedunculopontine nucleus in a
      patient with traumatic brain injury.
AB  - We report on a patient with traumatic brain injury who showed neural connection
      between injured cingulum and pedunculopontine nucleus on diffusion tensor
      tractography (DTT). A 74-year-old male who had suffered a traffic accident
      underwent conservative management for subarachnoid haemorrhage. Brain MRI which
      was performed 6 months after onset showed no specific lesions. On 6-month DTTs
      for cingulum of the patient, we observed discontinuations of both cingulums above
      the genu of corpus callosum. However, the left cingulum was connected to the left
      PPN via a neural tract that passed through the anterior corona radiata and
      thalamus. The neural connection between the injured cingulum and PPN seems to be
      a compensatory phenomenon for the destruction of cholinergic pathways from basal
      forebrain. We believe that this result might suggest one of recovery mechanisms
      of injured cingulum following brain injury.

PMID- 22951709
TI  - Motor impairments at presentation of clinically isolated syndrome suggestive of
      multiple sclerosis: Characterization of different disease subtypes.
AB  - OBJECTIVES: To evaluate the frequency of motor impairments in patients with
      recently diagnosed clinically isolated syndrome (CIS) suggestive of MS. METHODS:
      Following a neurological examination, patients with CIS were subdivided into two
      groups according to the number of functional systems involved at onset. Groups
      consisted of monosymptomatic (n=35, mean EDSS=1.3 +/- 0.2) and polysymptomatic
      (n=17, mean EDSS=2.6 +/- 0.1) patients. Motor assessment included peak isometric
      torque and fatigue index (FI) measured at the knee and ankle bilaterally and
      spatiotemporal parameters of gait and postural control. Lesion load and atrophy
      were measured on a 3.0T brain MRI using MSAnalyze computerized software. Twenty
      eight age- and gender-matched healthy subjects served as controls for motor
      assessment. RESULTS: Polysymptomatic patients demonstrated reduced peak strength
      and FI, slower gait velocity, narrower base of support and increased sway rate
      compared to healthy subjects and mono-symptomatic patients. Furthermore,
      polysymptomatic and monosymptomatic patient median score in T2-weighted volume
      lesions (mm<formula>^{3}</formula>) was 4875 and 1628, respectively. CONCLUSIONS:
      Evidence of two subtypes of CIS was established in context with MRI findings and
      motor deficits. Differentiating between these groups can potentially improve
      management of MS patients at the initial stages of the disease process.

PMID- 22951710
TI  - An adolescent with intact motor skills and intelligence after infant hemorrhagic
      stroke without rehabilitation therapy: a case report.
AB  - Devastating intracerebral hemorrhagic stroke is rarely encountered in children,
      but it has a high mortality rate. The case of a 15-year-old boy who survived a
      major stroke at 40 days old is described. He showed no significant motor or
      intelligence impairment in adolescence until he was hospitalized for transient
      left had tremors and slight left hand weakness caused by a cyst. The patient's
      almost complete motor recovery highlights the power of neural plasticity in young
      patients. The pediatric stroke was huge, but this did not affect his adolescent
      movement or intelligence, demonstrating the great neuroplastic potential of the
      developing human brain. These observations may help increase our knowledge about
      stroke in children and improve the treatment of pediatric stroke patients.

PMID- 22951711
TI  - Reliability of the Functional Reach Test and the influence of anthropometric
      characteristics on test results in subjects with hemiparesis.
AB  - First designed as an alternative method of assessing balance and susceptibility
      to falls among elderly, the Functional Reach Test (FR) has also been used among
      patients with hemiparesis. Then this study aimed to describe the intra- and inter
      rater and the test/re-test reliability of the FR measure in subjects with and
      without hemiparesis while verifying anthropometric influences on the
      measurements. The FR was administered to a sample of subjects with hemiparesis
      and to a control group that was matched by gender and age. A two-way analysis of
      variance was used to verify the intra-rater reliability. It was calculated using
      the differences between the averages of the measures obtained during single,
      double or triple trials. The intra-class correlation coefficient (ICC) was
      utilized and data plotted using the Bland-Altman method. Associations were
      analyzed using Pearson's correlation coefficient. In general, the intra-rater
      analysis did not show significant differences between the measures for the
      single, double or triple trials. Excellent ICC values were observed, and there
      were no significant associations with anthropometric parameters for the
      hemiparesis and control subjects. FR showed good reliability for patients with
      and without hemiparesis and the test measurements were not significantly
      associated with the anthropometric characteristics of the subjects.

PMID- 22951712
TI  - Contralesional cross-over in chronic neglect: visual search patterns reveal
      neglect of the ipsilesional hemispace.
AB  - INTRODUCTION: With neuropsychological rehabilitation approaches neglect patients
      can learn to compensate for the reduced awareness of the contralesional hemispace
      that is often observed after right brain damage. Here, we report contralesional
      "cross-over" deviations in line bisection that are hypothesized to be a result of
      focusing on the contralesional hemispace while the intact hemispace is
      "neglected". We investigate whether this unexpected pattern of deviation is
      related to defects in the visual field, motor intention/hypokinesia deficits or
      deficits in working memory. METHODS: Neglect patients with and without homonymous
      field defects were screened for contralesional cross-over deviations in line
      bisection of long lines. During line bisection eye movements were recorded in two
      conditions with and without requiring hand movements in order to search for
      directional hypokinesia. Visual fields were tested with near-threshold perimetry
      and with supra-threshold campimetry. RESULTS: Of 53 chronic neglect patients only
      8 showed cross-over in line bisection. Evidence for directional hypokinesia was
      found in only one patient. Patients with cross-over focused more often to the
      left than to the right of the objective line midpoint. Patients with and without
      visual field defects did not differ in the extent of cross-over deviations. Cross
      over deviation and inconsistent stimulus detection in left hemispace were
      correlated irrespective of the presence of a visual field deficit. Larger cross
      over deviations were associated with poorer verbal working memory span, and
      disorganized patterns of eye movement were related to reduced visuo-spatial
      working memory capacity. CONCLUSION: Increasing awareness of the disorder and the
      use of compensatory strategies may have led to a cross-over shift of visual
      search dominance towards the neglected side resulting in an exploration deficit
      of the ipsilesional side.

PMID- 22951713
TI  - Effects of forced use combined with scheduled home exercise program on upper
      extremity functioning in individuals with hemiparesis.
AB  - OBJECTIVES: The aims of this study were to 1) investigate the effects of forced
      use combined with scheduled home exercise program compared to forced use only on
      increasing upper extremity functioning, 2) examine whether increased upper
      extremity functioning generalized to activities of daily living (ADL)
      functioning, and 3) explore participants' psychosocial functioning. METHODS: A
      single-subject A-B-A'-C research design was employed in this study. The
      intervention consisted of two conditions: forced use only (intervention period
      B), and forced use in addtion to scheduled home exercise program (intervention
      period C). RESULTS: The results were as follows: 1) Forced use combined with
      scheduled home exercise program compared to forced use only allowed individuals
      with stroke to take part in exercise programs on their own within their home
      setting, ultimately improving their upper extremity functioning. 2) The program's
      promotion of performance in ADL tasks have the advantage of keeping participants
      focused so that a number of exercises can be maintained throughout the
      intervention. 3) Finally, forced use combined with scheduled home exercise
      program showed partial effects on improving the participants' psychosocial
      functioning. CONCLUSION: The results of the present study suggest that forced use
      combined with scheduled home exercise program compared to forced use only has the
      potential to be a cost- and resource-efficient method for intensifying
      rehabilitation.

PMID- 22951714
TI  - Treatment of hemispatial neglect in patients with post-hemiparesis: a single
      subject experimental design study using a whole-body tilt exercise plus mental
      practice.
AB  - PURPOSE: To investigate the effect of whole-body tilt exercise for treating
      hemispatial neglect and to identify the effects of incorporating mental practice
      into the exercise. METHODS: We used a single-subject experimental design
      alternating with multiple baselines. Three stroke patients with hemispatial
      neglect participated in this study. The severity of hemispatial neglect and
      balance function were measured during baseline and intervention sessions. The
      whole-body tilt exercise was performed by using a device that allows the body to
      tilt 20 degrees  from the neutral upright position. Mental practice consisted of
      5 min of relaxation, main whole-body tilt imagination, and normalization phases.
      RESULTS: When the whole-body tilt exercise alone was performed, the average
      severity score of hemispatial neglect in subjects 1, 2, and 3 decreased by 7.54,
      10.02, and 8.24, respectively; their respective average balance function score
      increased by 35.95%, 28.13%, and 15.33% under the open-eye condition and 34.66%,
      20.33%, and 13.77% under the closed-eye condition. For subjects 1, 2, and 3, the
      respective average hemispatial neglect score decreased by 9.07, 11.35, and 10.13
      after the whole-body tilt exercise with mental practice; their average balance
      function scores increased by 40.15%, 33.38%, and 24.22% under the open-eye
      condition and by 38.93%, 27.08%, and 11.88% under the closed-eye condition,
      respectively. CONCLUSION: These findings suggest that a whole-body tilt exercise
      alone may be beneficial in enhancing hemispatial neglect symptoms but the
      addition of mental practice produces a greater positive effect.

PMID- 22951715
TI  - The clinical characteristics of motor function in chronic hemiparetic stroke
      patients with complete corticospinal tract injury.
AB  - Clarification of the clinical characteristics of motor function in stroke
      patients with complete corticospinal tract (CST) injury would be of importance in
      stroke rehabilitation. However, this topic has not been clearly elucidated. We
      conducted an investigation of the clinical characteristics of motor function in
      chronic hemiparetic stroke patients with complete CST injury, as confirmed by
      transcranial magnetic stimulation and diffusion tensor imaging. Forty-one
      consecutive chronic hemiparetic stroke patients who showed an absence of motor
      evoked potential in muscles of the upper and lower extremities upon transcranial
      magnetic stimulation and in whom the integrity of the CST discontinued around
      stroke lesion on diffusion tensor imaging tractography were recruited. Mean
      Medical Research Council scores for distal musculature were lower than those for
      proximal musculature (P< 0.001). Mean Medical Research Council scores for upper
      extremity muscles were lower than those for lower extremity muscles (P< 0.001).
      The mean Motricity Index score for muscles of the upper extremities was lower
      than that for muscles of the lower extremities (P< 0.001). None of the patients
      had a functional hand; in contrast, 56% of patients were able to walk
      independently. We found that motor weaknesses of distal joint musculature and
      upper extremities were more severe than those of proximal joint musculature and
      lower extremities following complete injury of the CST in stroke, respectively.
      As a result, despite the absence of a functional hand in all patients, more than
      half were able to walk independently.

PMID- 22951716
TI  - Intra-rater reliability of the Modified Modified Ashworth Scale (MMAS) in the
      assessment of upper-limb muscle spasticity.
AB  - The aim of this study was to investigate the intra-rater reliability of the
      Modified Modified Ashworth Scale (MMAS) in the upper limb of patients with
      hemiparesis and to determine the effect of pain and contracture presence on the
      reliability of the MMAS. For this test-retest study 30 patients with hemiparesis
      were included. One physiotherapist using the MMAS, randomly rated the spasticity
      of shoulder adductors, elbow flexors, and wrist flexors in the affected upper
      limb of each patient with hemiparesis twice with at least a 1 week interval
      between testing sessions. The presence of pain and contracture during passive
      stretch was recorded. The magnitude of the contracture was measured by a
      goniometer. The quadratic weighted kappa statistics was very good for the upper
      limb spasticity (kappaw= 0.84). Intra-rater reliability was good for shoulder
      adductors (kappaw=0.75), and very good for elbow flexors and wrist flexors
      (kappaw 0.86 and 0.90, respectively). There were no differences between the
      weighted kappa values for muscle groups (p>0.05). The intra-rater reliability was
      also good in the presence of pain or contracture. The MMAS had very good intra
      rater reliability in the assessment of upper limb spasticity in patients with
      hemiparesis. The presence of pain during shoulder abduction or contracture of the
      shoulder adductors had no influence on the reliability of the MMAS (kappa w=0.75,
      0.77, respectively).

PMID- 22951717
TI  - Marrow-derived stromal cell delivery on fibrin microbeads can correct radiation
      induced wound-healing deficits.
AB  - Skin that is exposed to radiation has an impaired ability to heal wounds. This is
      especially true for whole-body irradiation, where even moderate nonlethal doses
      can result in wound-healing deficits. Our previous attempts to administer dermal
      cells locally to wounds to correct radiation-induced deficits were hampered by
      poor cell retention. Here we improve the outcome by using biodegradable fibrin
      microbeads (FMBs) to isolate a population of mesenchymal marrow-derived stromal
      cells (MSCs) from murine bone marrow by their specific binding to the fibrin
      matrix, culture them to high density in vitro, and deliver them as MSCs on FMBs
      at the wound site. MSCs are retained locally, proliferate in site, and assist
      wounds in gaining tensile strength in whole-body irradiated mice with or without
      additional skin-only exposure. MSC-FMBs were effective in two different mouse
      strains but were ineffective across a major histocompatability barrier.
      Remarkably, irradiated mice whose wounds were treated with MSC-FMBs showed
      enhanced hair regrowth, suggesting indirect effect on the correction of radiation
      induced follicular damage. Further studies showed that additional wound-healing
      benefit could be gained by administration of granulocyte colony-stimulating
      factor and AMD3100. Collagen strips coated with haptides and MSCs were also
      highly effective in correcting radiation-induced wound-healing deficits.

PMID- 22951718
TI  - Human beta-defensin 3 induces maturation of human langerhans cell-like dendritic
      cells: an antimicrobial peptide that functions as an endogenous adjuvant.
AB  - Human beta-defensins (hBDs) are antimicrobial peptides that have an important
      role in innate immune responses at epithelial barriers such as the skin. However,
      the role that hBDs have in initiating cellular immune responses that contribute
      to antigen-specific adaptive immunity is not well understood. Here we show that
      one member of the hBD family, hBD3, can induce maturation and T-helper type 1
      skewing function in human Langerhans cell-like dendritic cells (LC-DCs).
      Specifically, hBD3 potently induces phenotypic maturation of LC-DCs, including
      increased expression of CCR7, which mediates functional chemotactic responses to
      CCL19 and CCL21. hBD3-stimulated LC-DCs induce strong proliferation of and IFN
      gamma secretion by naive human T cells. hBD3 also induces phenotypic maturation
      of primary human skin-migratory DCs derived from human skin explants. These
      results suggest an important role for hBD3 in inducing DC activation, migration,
      and polarization. Thus, hBD3 contributes to the integration of innate and
      adaptive immune responses in the skin, and may be a useful adjuvant for skin
      immunization and an important factor in the pathophysiology of inflammatory skin
      diseases.

PMID- 22951719
TI  - An ex vivo model employing keloid-derived cell-seeded collagen sponges for
      therapy development.
AB  - The most distinctive feature of keloid is the extreme deposition of extracellular
      matrix, including collagens and proteoglycans (PGs). The focus of this study was
      the PG versican, which presumably defines keloid volume because of its ability to
      retain large amounts of water through its component glycosaminoglycans (GAGs).
      The excessive deposition of versican in keloids was examined by
      immunohistochemical analysis and by upregulation of the versican gene in these
      lesions by real-time PCR. The latter showed that mesenchymal cells derived from
      keloid lesion (KL) cells continue to exhibit above-normal versican production in
      culture. To establish a model of GAG deposition in keloids, collagen sponges
      seeded with KL cells (KL-SPos) were implanted in the subcutaneous space of nude
      mice. After 1 month, the KL-SPos were significantly heavier than the fibroblast
      (Fb)-seeded sponges (Fb-SPos). This ex vivo model was subsequently used to
      examine an inhibitory ability of IL-1beta that was identified to reduce versican
      in vitro. IL-1beta or chondroitinase ABC, when injected directly, successfully
      reduced the weight of the KL-SPos. Thus, on the basis of the change in weight of
      the seeded sponges, this ex vivo model can be used to test therapies aimed at
      reducing or inhibiting keloid formation and to study the pathogenesis of this
      aberrant response.

PMID- 22951720
TI  - Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK
      and CD8 T cells and restrains melanoma growth.
AB  - Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment.
      However, the putative contribution of anticancer immune responses in the efficacy
      of DTIC has not been evaluated. By testing how DTIC affects host immune responses
      to cancer in a mouse model of melanoma, we unexpectedly found that both natural
      killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect.
      Although DTIC did not directly affect immune cells, it triggered the upregulation
      of NKG2D ligands on tumor cells, leading to NK cell activation and IFNgamma
      secretion in mice and humans. NK cell-derived IFNgamma subsequently favored
      upregulation of major histocompatibility complex class I molecules on tumor
      cells, rendering them sensitive to cytotoxic CD8(+) T cells. Accordingly, DTIC
      markedly enhanced cytotoxic T lymphocyte antigen 4 inhibition efficacy in vivo in
      an NK-dependent manner. These results underscore the immunogenic properties of
      DTIC and provide a rationale to combine DTIC with immunotherapeutic agents that
      relieve immunosuppression in vivo.

PMID- 22951721
TI  - Aryl hydrocarbon receptor repressor (AhRR) function revisited: repression of CYP1
      activity in human skin fibroblasts is not related to AhRR expression.
AB  - The skin reacts to environmental noxae by inducing cytochrome P450 (CYP)
      catalyzed reactions via activation of the aryl hydrocarbon receptor (AhR). A
      drawback of this response is the generation of oxidative stress, which is
      especially dangerous for postreplicative cells such as dermal fibroblasts, in
      which damage may accumulate over time. Accordingly, in dermal fibroblasts, CYP1
      expression is repressed and it has been proposed that this is due to the AhR
      repressor (AhRR), which is supposedly overexpressed in fibroblasts as compared
      with other skin cells. Here, we revisited this "AhRR hypothesis", which has been
      mainly based on ectopic overexpression studies and correlation analyses of high
      AhRR gene expression with CYP1A1 repression in certain cell types. In primary
      human skin fibroblasts (NHDFs) of 25 individuals, we found that (i) the AhRR was
      expressed only at moderate RNA copy numbers and that, against the common view,
      (ii) in some fibroblast strains, CYP1A1 mRNA expression could be induced by AhR
      activators. However, even the highest induction did not translate into measurable
      CYP1 enzyme activity, and neither basal expression nor mRNA inducibility
      correlated with AhRR expression. In addition, enhancement of CYP1A1 mRNA
      expression by trichostatin A, which inhibits AhRR-recruited histone deacetylases
      at the CYP1A1 promoter, failed to induce measurable CYP1 activity. Finally, AhRR
      deficient ((-/-)) mouse embryonic fibroblasts were not induced to biologically
      relevant CYP1 enzyme activity despite impressive mRNA induction. These data
      clearly indicate that repressed CYP1 activity in NHDFs is not causally related to
      AhRR expression, which may serve a different, yet unknown, biological function.

PMID- 22951722
TI  - Melanoma cell invasiveness is promoted at least in part by the epidermal growth
      factor-like repeats of tenascin-C.
AB  - Tenascin-C (TNC), overexpressed in invasive growths, has been implicated in
      progression of melanoma, but the source and function of this molecule are not
      well defined. We found TNC expression at the front of invading melanoma cells,
      and that adding TNC to matrices enhances individual melanoma cell migration. As
      TNC is a multidomain protein, we examined the role of the TNC EGF-like (EGFL)
      repeats as these activate motogenic signaling cascades. We overexpressed a TNC
      fragment containing the assembly and EGFL domains of TNC (TNCEGFL). TNCEGFL
      expressing melanoma cells had lower speed and persistence in 2D migration assays
      due to a shift in the adhesion-contractility balance, as expression of TNCEGFL
      delayed melanoma cell attachment and spreading. The less adhesive phenotype was
      due, in part, to increased Rho-associated kinase (ROCK) signaling concomitant
      with myosin light chain 2 and MYPT phosphorylation. Inhibition of ROCK activity,
      which drives transcellular contractility, restored adhesion of TNCEGFL-expressing
      melanoma cells and increased their migration in 2D. In contrast to the diminished
      migration in 2D, TNCEGFL-expressing melanoma cells had higher invasive potential
      in Matrigel invasion assays, with cells expressing TNCEGFL having amoeboid
      morphology. Our findings suggest that melanoma-derived TNCEGFL exert a role in
      melanoma invasion by modulating ROCK signaling and cell migration.

PMID- 22951723
TI  - Epidermal growth factor facilitates melanoma lymph node metastasis by influencing
      tumor lymphangiogenesis.
AB  - Alterations in epidermal growth factor (EGF) expression are known to be of
      prognostic relevance in human melanoma, but EGF-mediated effects on melanoma have
      not been extensively studied. As lymph node metastasis usually represents the
      first major step in melanoma progression, we were trying to identify a potential
      role of primary tumor-derived EGF in the mediation of melanoma lymph node
      metastases. Stable EGF knockdown (EGFkd) in EGF-high (M24met) and EGF-low (A375)
      expressing melanoma cells was generated. Only in EGF-high melanoma cells, EGFkd
      led to a significant reduction of lymph node metastasis and primary tumor
      lymphangiogenesis in vivo, as well as impairment of tumor cell migration in
      vitro. Moreover, EGF-induced sprouting of lymphatic but not of blood endothelial
      cells was abolished using supernatants of M24met EGFkd cells. In addition, M24met
      EGFkd tumors showed reduced vascular endothelial growth factor-C (VEGF-C)
      expression levels. Similarly, in human primary melanomas, a direct correlation
      between EGF/VEGF-C and EGF/Prox-1 expression levels was found. Finally, melanoma
      patients with lymph node micrometastases undergoing sentinel node biopsy were
      found to have significantly elevated EGF serum levels as compared with sentinel
      lymph node-negative patients. Our data indicate that tumor-derived EGF is
      important in mediating melanoma lymph node metastasis.

PMID- 22951724
TI  - Linkage analysis of extended high-risk pedigrees replicates a cutaneous malignant
      melanoma predisposition locus on chromosome 9q21.
AB  - Three predisposition genes have been identified for cutaneous malignant melanoma
      (CMM), but they account for only ~25% of melanoma clusters/pedigrees. Linkage
      analyses of melanoma pedigrees from many countries have failed to identify
      significant linkage evidence for the remaining predisposition genes that must
      exist. The Utah linkage analysis approach of using singly informative extended
      high-risk pedigrees combined with high-density single-nucleotide polymorphism
      (SNP) markers has successfully identified significant linkage evidence for two
      regions. This is, to our knowledge, the first genome-wide linkage analysis of the
      extended Utah high-risk CMM pedigrees, and it provides confirmation of linkage
      for a chromosome 9q region previously reported in Danish pedigrees. This report
      confirms that linkage analysis for common disorders can be successful in analysis
      of high-density markers in sets of singly informative high-risk pedigrees.

PMID- 22951725
TI  - Association analyses identify three susceptibility Loci for vitiligo in the
      Chinese Han population.
AB  - To identify susceptibility loci for vitiligo, we extended our previous vitiligo
      genome-wide association study with a two-staged replication study that included
      6,857 cases and 12,025 controls from the Chinese Han population. We identified
      three susceptibility loci, 12q13.2 (rs10876864, P(combined)=8.07 * 10(-12), odds
      ratio (OR)=1.18), 11q23.3 (rs638893, P(combined)=2.47 * 10(-9), OR=1.22), and
      10q22.1 (rs1417210, P(combined)=1.83 * 10(-8), OR=0.88), and confirmed three
      previously reported loci for vitiligo, 3q28 (rs9851967, P(combined)=8.57 * 10(
      8), OR=0.88), 10p15.1 (rs3134883, P(combined)=1.01 * 10(-5), OR=1.11), and
      22q12.3 (rs2051582, P(combined)=2.12 * 10(-5), OR=1.14), in the Chinese Han
      population. The most significant single-nucleotide polymorphism in the 12q13.2
      locus is located immediately upstream of the promoter region of PMEL, which
      encodes a major melanocyte antigen and has expression loss in the vitiligo
      lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this
      study are also associated with other autoimmune diseases such as type 1 diabetes
      and systemic lupus erythematosus. These findings provide indirect support that
      vitiligo pathogenesis involves a complex interplay between immune regulatory
      factors and melanocyte-specific factors. They also highlight similarities and
      differences in the genetic basis of vitiligo in Chinese and Caucasian
      populations.

PMID- 22951726
TI  - An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in
      the absence of interleukin-17 receptor a signaling.
AB  - Topical application of imiquimod (IMQ) on the skin of mice induces inflammation
      with common features found in psoriatic skin. Recently, it was postulated that IL
      17 has an important role both in psoriasis and in the IMQ model. To further
      investigate the impact of IL-17RA signaling in psoriasis, we generated IL-17
      receptor A (IL-17RA)-deficient mice (IL-17RA(del)) and challenged these mice with
      IMQ. Interestingly, the disease was only partially reduced and delayed but not
      abolished when compared with controls. In the absence of IL-17RA, we found
      persisting signs of inflammation such as neutrophil and macrophage infiltration
      within the skin. Surprisingly, already in the naive state, the skin of IL
      17RA(del) mice contained significantly elevated numbers of Th17- and IL-17
      producing gammadelta T cells, assuming that IL-17RA signaling regulates the
      population size of Th17 and gammadelta T cells. Upon IMQ treatment of IL
      17RA(del) mice, these cells secreted elevated amounts of tumor necrosis factor
      alpha, IL-6, and IL-22, accompanied by increased levels of the chemokine CXCL2,
      suggesting an alternative pathway of neutrophil and macrophage skin infiltration.
      Hence, our findings have major implications in the potential long-term treatment
      of psoriasis by IL-17-targeting drugs.

PMID- 22951727
TI  - Pathophysiological characteristics of melanoma in-transit metastasis in a
      lymphedema mouse model.
AB  - In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor
      dissemination, characterized by the presence of melanoma cells between the
      primary lesion and the draining regional lymph node basin that is clinically
      associated with poor prognosis. In this study, we aimed to establish an
      experimental animal model of melanoma ITM, as research progress in this field has
      been hampered by a lack of suitable experimental models. We reproduced melanoma
      ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a
      mouse with lymphedema (LE). The tumor cells at the ITM site were highly
      proliferative, and mice with ITMs were more likely than control mice to develop
      distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor
      associated blood vessels were increased in the primary tumor site of the LE mice.
      Our established ITM melanoma mouse model enabled us to clarify the molecular
      determinants and pathophysiology of ITM. This ITM model is also comparable to the
      unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined
      the importance of lymphangiogenic factors in the tumor dissemination through the
      lymphatic system.

PMID- 22951728
TI  - IL-27 activates Th1-mediated responses in imiquimod-induced psoriasis-like skin
      lesions.
AB  - IL-27, a member of the IL-12 cytokine family, primes Th1 cell differentiation,
      whereas it suppresses Th17 cell development. We have previously reported that
      serum IL-27 levels are elevated in psoriatic patients and that IL-27 greatly
      induces in vitro production of Th1-type chemokines through STAT1 activation. In
      this study, to further investigate the in vivo role of IL-27 in the pathogenesis
      of psoriasis, we induced psoriasis-like inflammation on mouse back skin with
      topical application of imiquimod (IMQ), and continuously injected IL-27 or PBS
      subcutaneously. IMQ-treated skin showed an increase of IL-27 mRNA levels and the
      infiltration of IL-27-producing cells in the papillary dermis. The injection of
      IL-27 to the IMQ-treated skin exacerbated the disease compared with PBS
      injection. The IL-27 injection further augmented mRNA levels of IFN-gamma, CXCL9,
      CXCL10, CXCL11, and TNF-alpha, without altering those of IL-17A, IL-17F, IL-22,
      and CCL20. Finally, IL-27 antagonism attenuated the upregulation of IFN-gamma,
      CXCL9, CXCL10, CXCL11, and TNF-alpha mRNA levels, and induced clinical and
      histological improvement in the IMQ-treated skin. These results indicate that IL
      27 would act in a proinflammatory manner, and thereby exacerbate the psoriasis
      like skin inflammation induced by IMQ.

PMID- 22951729
TI  - Impaired proteasome function activates GATA3 in T cells and upregulates CTLA-4:
      relevance for Sezary syndrome.
AB  - Highly regulated expression of the negative costimulatory molecule cytotoxic T
      lymphocyte antigen-4 (CTLA-4) on T cells modulates T-cell activation and
      proliferation. CTLA-4 is preferentially expressed in Th2 T cells, whose
      differentiation depends on the transcriptional regulator GATA3. Sezary syndrome
      (SS) is a T-cell malignancy characterized by Th2 cytokine skewing, impaired T
      cell responses, and overexpression of GATA3 and CTLA-4. GATA3 is regulated by
      phosphorylation and ubiquitination. In SS cells, we detected increased
      polyubiquitinated proteins and activated GATA3. We hypothesized that proteasome
      dysfunction in SS T cells may lead to GATA3 and CTLA-4 overexpression. To test
      this hypothesis, we blocked proteasome function with bortezomib in normal T
      cells, and observed sustained GATA3 and CTLA-4 upregulation. The increased CTLA-4
      was functionally inhibitory in a mixed lymphocyte reaction (MLR). GATA3 directly
      transactivated the CTLA-4 promoter, and knockdown of GATA3 messenger RNA and
      protein inhibited CTLA-4 induction mediated by bortezomib. Finally, knockdown of
      GATA3 in patient's malignant T cells suppressed CTLA-4 expression. Here we
      demonstrate a new T-cell regulatory pathway that directly links decreased
      proteasome degradation of GATA3, CTLA-4 upregulation, and inhibition of T-cell
      responses. We also demonstrate the requirement of the GATA3/CTLA-4 regulatory
      pathway in fresh neoplastic CD4+ T cells. Targeting of this pathway may be
      beneficial in SS and other CTLA-4-overexpressing T-cell neoplasms.

PMID- 22951731
TI  - Epidermal inactivation of the glucocorticoid receptor triggers skin barrier
      defects and cutaneous inflammation.
AB  - The glucocorticoid (GC) receptor (GR) mediates the effects of physiological and
      pharmacological GC ligands and has a major role in cutaneous pathophysiology. To
      dissect the epithelial versus mesenchymal contribution of GR in developing and
      adult skin, we generated mice with keratinocyte-restricted GR inactivation (GR
      epidermal knockout or GR(EKO) mice). Developing and early postnatal GR(EKO) mice
      exhibited impaired epidermal barrier formation, abnormal keratinocyte
      differentiation, hyperproliferation, and stratum corneum (SC) fragility. At
      birth, GR(EKO) epidermis showed altered levels of epidermal differentiation
      complex genes, proteases and protease inhibitors which participate in SC
      maintenance, and innate immunity genes. Many upregulated genes, including
      S100a8/a9 and Tslp, also have increased expression in inflammatory skin diseases.
      Infiltration of macrophages and degranulating mast cells were observed in newborn
      GR(EKO) skin, hallmarks of atopic dermatitis. In addition to increased
      extracellular signal-regulated kinase activation, GR(EKO) newborn and adult
      epidermis had increased levels of phosphorylated signal transducer and activator
      of transcription 3, a feature of psoriasis. Although adult GR(EKO) epidermis had
      a mild phenotype of increased proliferation, perturbation of skin homeostasis
      with detergent or phorbol ester triggered an exaggerated proliferative and
      hyperkeratotic response relative to wild type. Together, our results show that
      epidermal loss of GR provokes skin barrier defects and cutaneous inflammation.

PMID- 22951730
TI  - Toll-like receptor 4 has an essential role in early skin wound healing.
AB  - Toll-like receptor 4 (TLR4) has a key role in the initiation of innate immunity
      and in the regulation of adaptive immune responses. Using microarray analysis and
      PCR, TLR4 expression was observed to increase in murine skin wounds at the early
      stages. The cellular location of TLR4 was primarily in keratinocytes at the wound
      edges. The closure of excisional wounds was significantly delayed in TLR4
      deficient (C3H/HeJ) as compared with wild-type mice, and both IL-1beta and IL-6
      production were significantly lower in the wounds of TLR4-deficient mice. EGF
      also markedly decreased in the wound edge of epidermis in TLR4-deficient mice. In
      vitro studies confirmed that a wound stimulus induces TLR4 mRNA expression in
      primary normal human epidermal keratinocytes (NHEK). In vitro injury also induced
      the phosphorylation of p38 and JNK MAPK (Jun N-terminal kinase mitogen-activated
      protein kinase) and the expression of IL-1beta and tumor necrosis factor-alpha by
      NHEK. Blockade of TLR4 delayed NHEK migration and abolished the phosphorylation
      of p38 and JNK MAPK, and blockade of TLR4 and/or p38/JNK abolished IL-1beta
      production. The results suggest that inflammatory cytokine production by injured
      NHEK is stimulated via the TLR4-p38 and JNK MAPK signaling pathway. Together, the
      results provide evidence for a role of TLR4 at sites of injury, and suggest that
      TLR4 is an important regulator of wound inflammation.

PMID- 22951732
TI  - Reduced WIF-1 expression stimulates skin hyperpigmentation in patients with
      melasma.
AB  - The expression of Wnt inhibitory factor-1 (WIF-1) gene, which was detected by a
      microarray analysis of hyperpigmented and normally pigmented skin sets of melasma
      patients, was significantly reduced in the hyperpigmented skin from melasma
      patients, but not in healthy controls, regardless of UV irradiation. Wnt signals
      regulate skin pigmentation; however, WIF-1 is expressed in cultured skin
      keratinocytes and fibroblasts, but not in melanocytes. Therefore, we examined
      whether WIF-1 knockdown in neighboring keratinocytes and fibroblasts plays a role
      in melasma. Additionally, the effect of WIF-1 overexpression on the amelioration
      of hyperpigmentation was examined. WIF-1 knockdown, either in fibroblasts or in
      keratinocytes, significantly stimulated tyrosinase expression and melanosome
      transfer, whereas melanocytes with WIF-1 overexpression significantly reduced
      those parameters. The WIF-1 knockdown decreased glycogen synthase kinase-3beta
      (GSK-3beta), beta-catenin, and NFATc2 (nuclear factor of activated T cells,
      cytoplasmic, calcineurin-dependent 2) phosphorylation and increased
      microphthalmia-associated transcription factor (MITF) expression as in
      melanocytes with Wnt-1 overexpression, whereas the WIF-1 overexpression reversed
      the results. Expression of Wnts, both canonical and noncanonical, was increased
      in the hyperpigmented skin of melasma patients. Collectively, WIF-1
      downregulation, which may occur in epidermal keratinocytes and in dermal
      fibroblasts, is involved in melasma development because of the stimulation of
      melanogenesis and melanosome transfer through upregulation of the canonical and
      the noncanonical Wnt signaling pathway.

PMID- 22951733
TI  - Repeated trans-watershed hybridization among haplochromine cichlids (Cichlidae)
      was triggered by Neogene landscape evolution.
AB  - The megadiverse haplochromine cichlid radiations of the East African lakes,
      famous examples of explosive speciation and adaptive radiation, are according to
      recent studies, introgressed by different riverine lineages. This study is based
      on the first comprehensive mitochondrial and nuclear DNA dataset from extensive
      sampling of riverine haplochromine cichlids. It includes species from the lower
      River Congo and Angolan (River Kwanza) drainages. Reconstruction of phylogenetic
      hypotheses revealed the paradox of clearly discordant phylogenetic signals.
      Closely related mtDNA haplotypes are distributed thousands of kilometres apart
      and across major African watersheds, whereas some neighbouring species carry
      drastically divergent mtDNA haplotypes. At shallow and deep phylogenetic layers,
      strong signals of hybridization are attributed to the complex Late Miocene/Early
      Pliocene palaeohistory of African rivers. Hybridization of multiple lineages
      across changing watersheds shaped each of the major haplochromine radiations in
      lakes Tanganyika, Victoria, Malawi and the Kalahari Palaeolakes, as well as a
      miniature species flock in the Congo basin (River Fwa). On the basis of our
      results, introgression occurred not only on a spatially restricted scale, but
      massively over almost the whole range of the haplochromine distribution. This
      provides an alternative view on the origin and exceptional high diversity of this
      enigmatic vertebrate group.

PMID- 22951734
TI  - Phanerozoic marine diversity: rock record modelling provides an independent test
      of large-scale trends.
AB  - Sampling bias created by a heterogeneous rock record can seriously distort
      estimates of marine diversity and makes a direct reading of the fossil record
      unreliable. Here we compare two independent estimates of Phanerozoic marine
      diversity that explicitly take account of variation in sampling-a subsampling
      approach that standardizes for differences in fossil collection intensity, and a
      rock area modelling approach that takes account of differences in rock
      availability. Using the fossil records of North America and Western Europe, we
      demonstrate that a modelling approach applied to the combined data produces
      results that are significantly correlated with those derived from subsampling.
      This concordance between independent approaches argues strongly for the reality
      of the large-scale trends in diversity we identify from both approaches.

PMID- 22951736
TI  - Avoidance of roads and selection for recent cutovers by threatened caribou:
      fitness-rewarding or maladaptive behaviour?
AB  - The impact of anthropogenic disturbance on the fitness of prey should depend on
      the relative effect of human activities on different trophic levels. This
      verification remains rare, however, especially for large animals. We investigated
      the functional link between habitat selection of female caribou (Rangifer
      tarandus) and the survival of their calves, a fitness correlate. This top-down
      controlled population of the threatened forest-dwelling caribou inhabits a
      managed forest occupied by wolves (Canis lupus) and black bears (Ursus
      americanus). Sixty-one per cent of calves died from bear predation within two
      months following their birth. Variation in habitat selection tactics among
      mothers resulted in different mortality risks for their calves. When calves
      occupied areas with few deciduous trees, they were more likely to die from
      predation if the local road density was high. Although caribou are typically
      associated with pristine forests, females selected recent cutovers without
      negative impact on calf survival. This selection became detrimental, however, as
      regeneration took place in harvested stands owing to increased bear predation. We
      demonstrate that human disturbance has asymmetrical consequences on the trophic
      levels of a food web involving multiple large mammals, which resulted in habitat
      selection tactics with a greater short-term fitness payoff and, therefore, with
      higher evolutionary opportunity.

PMID- 22951735
TI  - Intraguild predation provides a selection mechanism for bacterial antagonistic
      compounds.
AB  - Bacteriocins are bacterial proteinaceous toxins with bacteriostatic or
      bacteriocidal activity towards other bacteria. The current theory on their
      biological role concerns especially colicins, with underlying social interactions
      described as an example of spite. This leads to a rock-paper-scissors game
      between colicin producers and sensitive and resistant variants. The generality of
      this type of selection mechanism has previously been challenged with lactic acid
      bacterial (LAB) bacteriocins as an example. In the natural environment of LAB,
      batch cultures are the norm opposed to the natural habitats of Escherichia coli
      where continuous cultures are prevailing. This implies that fitness for LAB, to a
      large degree, is related to survival rates (bottleneck situations) rather than to
      growth rates. We suggest that the biological role of LAB bacteriocins is to
      enhance survival in the stationary growth phase by securing a supply of nutrients
      from lysed target cells. Thus, this social interaction is an example of
      selfishness rather than of spite. Specifically, it fits into an ecological model
      known as intraguild predation (IGP), which is a combination of competition and
      predation where the predator (LAB bacteriocin producer) and prey (bacteriocin
      susceptible bacteria) share similar and often limited resources. We hypothesize
      that IGP may be a common phenomenon promoting microbial production of
      antagonistic compounds.

PMID- 22951737
TI  - Major histocompatibility complex class II compatibility, but not class I,
      predicts mate choice in a bird with highly developed olfaction.
AB  - Mate choice for major histocompatibility complex (MHC) compatibility has been
      found in several taxa, although rarely in birds. MHC is a crucial component in
      adaptive immunity and by choosing an MHC-dissimilar partner, heterozygosity and
      potentially broad pathogen resistance is maximized in the offspring. The MHC
      genotype influences odour cues and preferences in mammals and fish and hence
      olfactory-based mate choice can occur. We tested whether blue petrels, Halobaena
      caerulea, choose partners based on MHC compatibility. This bird is long-lived,
      monogamous and can discriminate between individual odours using olfaction, which
      makes it exceptionally well suited for this analysis. We screened MHC class I and
      II B alleles in blue petrels using 454-pyrosequencing and quantified the
      phylogenetic, functional and allele-sharing similarity between individuals.
      Partners were functionally more dissimilar at the MHC class II B loci than
      expected from random mating (p = 0.033), whereas there was no such difference at
      the MHC class I loci. Phylogenetic and non-sequence-based MHC allele-sharing
      measures detected no MHC dissimilarity between partners for either MHC class I or
      II B. Our study provides evidence of mate choice for MHC compatibility in a bird
      with a high dependency on odour cues, suggesting that MHC odour-mediated mate
      choice occurs in birds.

PMID- 22951738
TI  - Rapid evolution of Wolbachia incompatibility types.
AB  - In most insects, the endosymbiont Wolbachia induces cytoplasmic incompatibility
      (CI), an embryonic mortality observed when infected males mate either with
      uninfected females or with females infected by an incompatible Wolbachia strain.
      Although the molecular mechanism of CI remains elusive, it is classically viewed
      as a modification-rescue model, in which a Wolbachia mod function disables the
      reproductive success of the sperm of infected males, unless eggs are infected and
      express a compatible resc function. The extent to which the modification-rescue
      model can predict highly complex CI pattern remains a challenging issue. Here, we
      show the rapid evolution of the mod-resc system in the Culex pipiens mosquito. We
      have surveyed four incompatible laboratory isofemale lines over 50 generations
      and observed in two of them that CI has evolved from complete to partial
      incompatibility (i.e. the production of a mixture of compatible and incompatible
      clutches). Emergence of the new CI types depends only on Wolbachia determinants
      and can be simply explained by the gain of new resc functions. Evolution of CI
      types in Cx. pipiens thus appears as a gradual process, in which one or several
      resc functions can coexist in the same individual host in addition to the ones
      involved in the self-compatibility. Our data identified CI as a very dynamic
      process. We suggest that ancestral and mutant Wolbachia expressing distinct resc
      functions can co-infect individual hosts, opening the possibility for the mod
      functions to evolve subsequently. This gives a first clue towards the
      understanding of how Wolbachia reached highly complex CI pattern in host
      populations.

PMID- 22951739
TI  - Auditory sequence analysis and phonological skill.
AB  - This work tests the relationship between auditory and phonological skill in a non
      selected cohort of 238 school students (age 11) with the specific hypothesis that
      sound-sequence analysis would be more relevant to phonological skill than the
      analysis of basic, single sounds. Auditory processing was assessed across the
      domains of pitch, time and timbre; a combination of six standard tests of
      literacy and language ability was used to assess phonological skill. A
      significant correlation between general auditory and phonological skill was
      demonstrated, plus a significant, specific correlation between measures of
      phonological skill and the auditory analysis of short sequences in pitch and
      time. The data support a limited but significant link between auditory and
      phonological ability with a specific role for sound-sequence analysis, and
      provide a possible new focus for auditory training strategies to aid language
      development in early adolescence.

PMID- 22951740
TI  - Ready steady slow: action preparation slows the subjective passage of time.
AB  - Professional ball game players report the feeling of the ball 'slowing-down'
      before hitting it. Because effective motor preparation is critical in achieving
      such expert motor performance, these anecdotal comments imply that the subjective
      passage of time may be influenced by preparation for action. Previous reports of
      temporal illusions associated with action generally emphasize compensation for
      suppressed sensory signals that accompany motor commands. Here, we show that the
      time is perceived slowed-down during preparation of a ballistic reaching movement
      before action, involving enhancement of sensory processing. Preparing for a
      reaching movement increased perceived duration of a visual stimulus. This effect
      was tightly linked to action preparation, because the amount of temporal dilation
      increased with the information about the upcoming movement. Furthermore, we
      showed a reduction of perceived frequency for flickering stimuli and an enhanced
      detection of rapidly presented letters during action preparation, suggesting
      increased temporal resolution of visual perception during action preparation. We
      propose that the temporal dilation during action preparation reflects the
      function of the brain to maximize the capacity of sensory information-acquisition
      prior to execution of a ballistic movement. This strategy might facilitate
      changing or inhibiting the planned action in response to last-minute changes in
      the external environment.

PMID- 22951741
TI  - Social discrimination by quantitative assessment of immunogenetic similarity.
AB  - Genes of the major histocompatibility complex (MHC) that underlie the adaptive
      immune system may allow vertebrates to recognize their kin. True kin-recognition
      genes should produce signalling products to which organisms can respond. Allelic
      variation in the peptide-binding region (PBR) of MHC molecules determines the
      pool of peptides that can be presented to trigger an immune response. To examine
      whether these MHC peptides also might underlie assessments of genetic similarity,
      we tested whether Xenopus laevis tadpoles socially discriminate between pairs of
      siblings with which they differed in PBR amino acid sequences. We found that
      tadpoles (four sibships, n = 854) associated preferentially with siblings with
      which they were more similar in PBR amino acid sequence. Moreover, the strength
      of their preference for a conspecific was directly proportional to the sequence
      similarity between them. Discrimination was graded, and correlated more closely
      with functional sequence differences encoded by MHC class I and class II alleles
      than with numbers of shared haplotypes. Our results thus suggest that haplotype
      analyses may fail to reveal fine-scale behavioural responses to divergence in
      functionally expressed sequences. We conclude that MHC-PBR gene products mediate
      quantitative social assessment of immunogenetic similarity that may facilitate
      kin recognition in vertebrates.

PMID- 22951742
TI  - Exploratory behaviour and stressor hyper-responsiveness facilitate range
      expansion of an introduced songbird.
AB  - Global anthropogenic changes are occurring at an unprecedented rate; one change,
      human-facilitated introduction of species outside their native range, has had
      significant ecological and economic impacts. Surprisingly, what traits facilitate
      range expansions post-introduction is relatively unknown. This information could
      help predict future expansions of introduced species as well as native species
      shifting their ranges as climate conditions change. Here, we asked whether
      specific behavioural and physiological traits were important in the ongoing
      expansion of house sparrows (Passer domesticus) across Kenya. We predicted that
      birds at the site of initial introduction (Mombasa, introduced approx. 1950)
      would behave and regulate corticosterone, a stress hormone, differently than
      birds at the range edge (Kakamega, approx. 885 km from Mombasa; colonized within
      the last 5 years). Specifically, we predicted greater exploratory behaviour and
      stronger corticosterone response to stressors in birds at the range edge, which
      may facilitate the identification, resolution and memory of stressors. Indeed, we
      found that distance from Mombasa (a proxy for population age) was a strong
      predictor of both exploratory behaviour and corticosterone release in response to
      restraint (but only while birds were breeding). These results suggest that
      certain behavioural and neuroendocrine traits may influence the ability of
      species to colonize novel habitats.

PMID- 22951743
TI  - The yield of experimental yeast populations declines during selection.
AB  - The trade-off between growth rate and yield can limit population productivity.
      Here we tested for this life-history trade-off in replicate haploid and diploid
      populations of Saccharomyces cerevisiae propagated in glucose-limited medium in
      batch cultures for 5000 generations. The yield of single clones isolated from the
      haploid lineages, measured as both optical and population density at the end of a
      growth cycle, declined during selection and was negatively correlated with growth
      rate. Initially, diploid populations did not pay this cost of adaptation but
      haploidized after about 1000-3000 generations of selection, and this ploidy
      transition was associated with a decline in yield caused by reduced cell size.
      These results demonstrate the experimental evolution of a trade-off between
      growth rate and yield, caused by antagonistic pleiotropy, during adaptation in
      haploids and after an adaptive transition from diploidy to haploidy.

PMID- 22951744
TI  - Human selection of elk behavioural traits in a landscape of fear.
AB  - Among agents of selection that shape phenotypic traits in animals, humans can
      cause more rapid changes than many natural factors. Studies have focused on human
      selection of morphological traits, but little is known about human selection of
      behavioural traits. By monitoring elk (Cervus elaphus) with satellite telemetry,
      we tested whether individuals harvested by hunters adopted less favourable
      behaviours than elk that survived the hunting season. Among 45 2-year-old males,
      harvested elk showed bolder behaviour, including higher movement rate and
      increased use of open areas, compared with surviving elk that showed less
      conspicuous behaviour. Personality clearly drove this pattern, given that inter
      individual differences in movement rate were present before the onset of the
      hunting season. Elk that were harvested further increased their movement rate
      when the probability of encountering hunters was high (close to roads, flatter
      terrain, during the weekend), while elk that survived decreased movements and
      showed avoidance of open areas. Among 77 females (2-19 y.o.), personality traits
      were less evident and likely confounded by learning because females decreased
      their movement rate with increasing age. As with males, hunters typically
      harvested females with bold behavioural traits. Among less-experienced elk (2-9
      y.o.), females that moved faster were harvested, while elk that moved slower and
      avoided open areas survived. Interestingly, movement rate decreased as age
      increased in those females that survived, but not in those that were eventually
      harvested. The latter clearly showed lower plasticity and adaptability to the
      local environment. All females older than 9 y.o. moved more slowly, avoided open
      areas and survived. Selection on behavioural traits is an important but often
      ignored consequence of human exploitation of wild animals. Human hunting could
      evoke exploitation-induced evolutionary change, which, in turn, might oppose
      adaptive responses to natural and sexual selection.

PMID- 22951745
TI  - Bottom-up effects of host-plant species diversity and top-down effects of ants
      interactively increase plant performance.
AB  - While plant diversity is well known to increase primary productivity, whether
      these bottom-up effects are enhanced by reciprocal top-down effects from the
      third trophic level is unknown. We studied whether pine tree species diversity,
      aphid-tending ants and their interaction determined plant performance and
      arthropod community structure. Plant diversity had a positive effect on aphids,
      but only in the presence of mutualistic ants, leading to a threefold greater
      number of both groups in the tri-specific cultures than in monocultures. Plant
      diversity increased ant abundance not only by increasing aphid number, but also
      by increasing ant recruitment per aphid. The positive effect of diversity on ants
      in turn cascaded down to increase plant performance; diversity increased plant
      growth (but not biomass), and this effect was stronger in the presence of ants.
      Consequently, bottom-up effects of diversity within the same genus and guild of
      plants, and top-down effects from the third trophic level (predatory ants),
      interactively increased plant performance.

PMID- 22951746
TI  - Tissue loss (white syndrome) in the coral Montipora capitata is a dynamic disease
      with multiple host responses and potential causes.
AB  - Tissue loss diseases or white syndromes (WS) are some of the most important coral
      diseases because they result in significant colony mortality and morbidity,
      threatening dominant Acroporidae in the Caribbean and Pacific. The causes of WS
      remain elusive in part because few have examined affected corals at the cellular
      level. We studied the cellular changes associated with WS over time in a dominant
      Hawaiian coral, Montipora capitata, and showed that: (i) WS has rapidly
      progressing (acute) phases mainly associated with ciliates or slowly progressing
      (chronic) phases mainly associated with helminths or chimeric parasites; (ii)
      these phases interchanged and waxed and waned; (iii) WS could be a systemic
      disease associated with chimeric parasitism or a localized disease associated
      with helminths or ciliates; (iv) corals responded to ciliates mainly with
      necrosis and to helminths or chimeric parasites with wound repair; (v) mixed
      infections were uncommon; and (vi) other than cyanobacteria, prokaryotes
      associated with cell death were not seen. Recognizing potential agents associated
      with disease at the cellular level and the host response to those agents offers a
      logical deductive rationale to further explore the role of such agents in the
      pathogenesis of WS in M. capitata and helps explain manifestation of gross
      lesions. This approach has broad applicability to the study of the pathogenesis
      of coral diseases in the field and under experimental settings.

PMID- 22951748
TI  - Make a decision, please!

PMID- 22951747
TI  - In vivo assessment of CdSe-ZnS quantum dots: coating dependent bioaccumulation
      and genotoxicity.
AB  - Semiconductor nanocrystals, or Quantum Dots (QDs), have gained considerable
      attention due to their unique size-dependent optical and electronic properties
      that make them attractive for a wide range of applications, including biology and
      nanomedicine. Their widespread use, however, poses urgent questions about their
      potential toxicity, especially because of their heavy metal composition that
      could cause harmful effects to human health and environment. In this work, we
      evaluated in vivo the long-term toxicity of CdSe-ZnS QDs with different surface
      coatings, probing oral administration in the model system Drosophila
      melanogaster. In particular, we found that all the differently coated QDs
      significantly affect the lifespan of treated Drosophila populations and induce a
      marked increase in reactive oxygen species (ROS) levels. Furthermore, we observed
      that these QDs induce severe genotoxic effects and increased rate of apoptosis in
      Drosophila haemocytes. These toxic effects were found to be mainly related to the
      in vivo degradation of QDs with consequent release of Cd(2+) ions, while the
      coating of QDs can modulate their bioaccumulation in the organism, partly
      decreasing their overall toxicity.

PMID- 22951750
TI  - Analysis of 10 X-STRs in three population groups from Ecuador.

PMID- 22951749
TI  - Ifosfamide, carboplatin, and etoposide for neuroblastoma: a high-dose salvage
      regimen and review of the literature.
AB  - BACKGROUND: The authors report a retrospective analysis of high-dose ifosfamide,
      carboplatin, and etoposide (HD-ICE) for patients with refractory or relapsed
      neuroblastoma (NB). A major reason for using this regimen was the long time since
      patients received previous treatment with a platinum compound. The authors also
      summarized the published experience on ICE in patients with NB. METHODS:
      Treatment comprised ifosfamide (2000 mg/m(2) daily for 5 days), carboplatin (500
      mg/m(2) daily for 2 days), and etoposide (100 mg/m(2) daily for 5 days). Patients
      who had poor hematologic reserve (platelet count <100,000/MUL) from previous
      therapy received peripheral blood stem cells (PBSCs) after HD-ICE. Disease status
      before and after HD-ICE was defined according to International Neuroblastoma
      Response Criteria (expanded to include (123) I-metaiodobenzylguanidine findings).
      Publications that were informative about ICE for NB were reviewed. RESULTS:
      Seventy-four patients received 92 cycles of ICE, including 37 patients who
      received PBSC rescue. Grade 3 toxicities were rare: 1-3 patients had
      encephalopathy, mucositis, or gastroenteritis. Bacteremia was documented in 24 of
      92 cycles (26%). The absolute neutrophil count reached 500/MUL on day 17-30
      (median, day 22) in patients who had satisfactory hematologic reserve. Disease
      regressions (major and minor responses) were achieved by 14 of 17 patients (82%)
      with a new relapse, 13 of 26 patients (50%) with refractory NB, and 12 of 34
      patients (35%) who were treated for progressive disease during chemotherapy (P =
      .005). In the literature, patients received ICE at lower dosages and achieved
      major response rates >36% in phase 1 and 2 studies (in which less comprehensive
      staging evaluations were used) that involved resistant NB and >70% in induction
      for newly diagnosed NB. CONCLUSIONS: HD-ICE is appealing as salvage treatment or
      consolidative therapy because of its anti-NB activity and the low risk of major
      nonhematologic toxicity. PBSC support is unnecessary for patients who had intact
      hematologic reserve.

PMID- 22951751
TI  - Effect of hyperbaric oxygen treatment on tendon healing after Achilles tendon
      repair: an experimental study on rats.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric
      oxygen treatment on early tendon healing in the treatment of Achilles tendon
      ruptures. METHODS: Fifty-six male Wistar albino rats were randomized and divided
      into two groups. Intratendinous betamethasone was administered preoperatively for
      degeneration in 28 rats and isotonic saline injection was administered to the
      remaining 28 rats. The Achilles tendons of all rats were sutured following
      tenotomy. Fourteen rats from each group were then selected and received
      hyperbaric oxygen therapy. The Achilles tendons were removed, biomechanically
      evaluated and histopathologically studied on the 11th postoperative day. The
      biomechanical properties and amount of fibrosis, inflammation and vascularization
      were compared between the groups receiving hyperbaric oxygen therapy and those
      not. RESULTS: Histopathological study showed the amount of fibrosis was
      significantly higher in the hyperbaric oxygen therapy group than in the control
      group without the hyperbaric oxygen therapy. The amount of inflammation and
      vascularization were significantly higher in the steroid administration group
      than in the no-steroid group. There was a significant difference in the
      biomechanical properties of the groups in terms of maximum force, stiffness,
      elastic modulus and maximum allowable stress. CONCLUSION: Hyperbaric oxygen
      therapy creates a positive histological and biomechanical effect on tendon
      healing after Achilles tendon repair.

PMID- 22951752
TI  - Evaluation of shoulder and elbow functions after treatment of humeral shaft
      fractures: a 20-132-month follow-up study.
AB  - OBJECTIVE: The aim of this study was to evaluate the long-term results of
      shoulder and elbow functions in humeral shaft fractures treated with functional
      brace, plate and screw osteosynthesis or intramedullary nailing. METHODS: The
      study included 128 patients treated for humeral shaft fracture. The patients were
      divided into three groups according to treatment method: Group 1 (n=62) received
      functional brace, Group 2 (n=36) plate and screw osteosynthesis and Group 3
      (n=30) intramedullary nailing. Coronal and sagittal humeral angulations were
      measured radiologically during the final follow-up. Shoulder and elbow functions
      were evaluated using the Constant shoulder score, the Mayo Elbow Performance
      Scoring and range of movement measurements. RESULTS: The mean follow-up time was
      74 (range: 20 to 132) months. Mean Constant shoulder scores were 92.4 in Group 1,
      85.6 in Group 2 and 74 in Group 3. A statistically significant difference was
      detected between the Constant shoulder scores of Groups 2 and 3 (p<0.05). In the
      last follow-up, the mean Mayo Elbow Performance Score of Group 1 was 96.9, Group
      2 was 95.7 and Group 3 was 89.2. Statistically significant differences were not
      detected between the Group 2 and 3 (p>0.05). In the statistical evaluation of the
      Constant shoulder scores, a statistically significant difference was detected
      between the Constant scores of patients with a varus angulation greater than 20
      degrees  and those with neutral alignment. CONCLUSION: Functional results of
      humeral shaft fractures treated with functional brace appear to be satisfactory.
      Varus and antecurvatum may affect shoulder and elbow function. In the presence of
      surgical indications, plate and screw fixation technique is the most effective
      method in terms of shoulder and elbow functions.

PMID- 22951753
TI  - Locked anatomic plate fixation in displaced clavicular fractures.
AB  - OBJECTIVE: We aimed to evaluate the results and complications of open reduction
      and internal fixation by locked anatomic plates in adult midshaft clavicular
      fractures. METHODS: Sixteen patients (11 males, 5 females; mean age: 39.6 years)
      who underwent open reduction and internal fixation with locked anatomic plate for
      displaced-comminuted midshaft clavicular fractures and were followed-up for at
      least one year were reviewed retrospectively. Complications in the early and late
      postoperative periods and functional scores according to the Constant and DASH
      scoring systems from the latest follow-up were evaluated. RESULTS: Mean follow-up
      period was 24.6 (range: 12 to 52) months and mean union time was 13.3 (range: 10
      to 23) weeks. None of the patients had superficial and/or deep infections in the
      early postoperative period or neurovascular complications. Two (12.5%) patients
      had implant irritation. In two (12.5%) patients, implant failure was detected in
      the late postoperative period. Delayed union was suspected in these patients and
      they were operated with longer plate and grafting in the 4th month. At the final
      follow-up, none of the patients had nonunion or malunion and the mean Constant
      and DASH scores were 85.5 and 12.8, respectively. Constant scores in patients
      with complications (p=0.007) and DASH scores in patients with no complications
      (p=0.001) were significantly lower. CONCLUSION: Fixation with locked anatomic
      plates in displaced midshaft clavicular fractures has lower complication rates.
      Possible postoperative complications are generally associated with implant
      irritation and failure. These problems can be avoided with the development in
      implant technology and new implant designs.

PMID- 22951754
TI  - Subcutaneous anterior transposition of the ulnar nerve in cubital tunnel
      syndrome.
AB  - OBJECTIVE: The aim of this study was to present the mid-to long-term results of
      subcutaneous anterior transposition of the ulnar nerve in the treatment of
      cubital tunnel syndrome. METHODS: The study retrospectively evaluated 33 patients
      (24 males, 9 females; mean age: 48 years; range: 26 to 59 years) who underwent
      subcutaneous transposition of the ulnar nerve. Mean follow-up period was 4 years
      9 months (range: 2 years 6 months to 8 years). Modified McGowan's classification
      was used for preoperative scoring and the Wilson & Krout classification for
      postoperative clinical evaluation. Preoperatively 5 patients (15%) had Grade 1, 7
      (21%) had Grade 2A, 9 (27%) had Grade 2B, and 12 (36%) had Grade 3 neuropathy.
      RESULTS: There were excellent results in 24 patients (73%), good in 7 (21%), fair
      in 1 (3%), and poor in one (3%). The patient with the poor result had developed
      neuropathy following a crush injury. There was a negative correlation between the
      preoperative McGowan grade and the postoperative Wilson & Krout score (p<0.05, r=
      0.43). The success rate of the operation was significantly lower in patient
      groups as the time from symptom onset increased (p<0.05). There were no
      complications. CONCLUSION: Subcutaneous anterior transposition of the ulnar nerve
      is an effective and reliable surgical method with a low complication rate for the
      treatment of cubital tunnel syndrome.

PMID- 22951755
TI  - Preoperative cardiac evaluation in proximal femur fractures and its effects on
      the surgical outcome.
AB  - OBJECTIVE: The aim of the current study was to evaluate the impact of cardiac
      risk stratification and preoperative cardiac evaluation on final outcomes in
      patients with acute proximal femur fractures. METHODS: This retrospective review
      included one hundred and three patients who underwent a preoperative cardiac
      evaluation prior to proximal femur fracture operation between 2004 and 2007 at a
      tertiary care hospital. Patients were divided into two groups. Group A included
      76 patients who were tested with ECG only and Group B included 27 patients with
      additional clearance. All of these files were reviewed according to a set pro
      forma. Statistical analysis was done using the SPSS 17 software. The Student's t
      test and Mann-Whitney U test were applied to compare two means. RESULTS: Fifty
      three patients had intertrochanteric fractures and 50 had femoral neck fractures.
      Only 7 patients had a metabolic equivalent task of less than 4. Group B patients
      had significant delay in time from triage to surgery (p<0.0001) and from surgery
      to ambulation (p<0.005). Group B patients also had an increased length of
      hospital stay, although no significant effect on perioperative mortality was
      observed. CONCLUSION: Preoperative cardiac evaluation is associated with delay in
      surgery and subsequent ambulation. Delay in surgery is not associated with
      increased perioperative mortality at our institute. However, the set of
      guidelines proposed by ACC/AHA should be followed, as the selection of patients
      for additional investigation was not justifiable in most cases.

PMID- 22951756
TI  - Surgical practices in total knee arthroplasty in Turkey.
AB  - OBJECTIVE: The aim of this study was to determine the current practices in the
      total knee arthroplasty (TKA) and the differences of practice among the
      orthopedic surgeons in Turkey. METHODS: Data in this cross-sectional and
      descriptive study was collected through a questionnaire from 76 orthopaedic
      surgeons performing TKA. The questionnaire form contained 57 questions under four
      main headings, covering the professional properties of the surgeon, pre-surgery
      approach, surgical technique applied for TKA and the surgical details peculiar to
      the technique with solutions applied for complication scenarios, and finally the
      postoperative approach. RESULTS: It was determined that 39.7% of the TKA
      applications were performed in operating theatres without laminar airflow or HEPA
      filters. Nearly 1/5 of the surgeons used more than one antibiotic for
      prophylaxis, and more than 85% continued prophylaxis use over 3 days. Low
      molecular-weight heparin was the most commonly used method for
      thromboprophylaxis. 94.67% of the surgeons used only the cemented technique in
      primary TKA. 44% indicated that they performed simultaneous bilateral
      arthroplasty, 89% did not use any scoring system and 72.37% preferred fixed
      bearing and posterior-cruciate-retaining type prosthesis. CONCLUSION: Results
      showed no standardization in TKA surgery among surgeons in Turkey, and important
      educational deficiencies were noted.

PMID- 22951757
TI  - Evaluation of functionality in acquired and congenital upper extremity child
      amputees.
AB  - OBJECTIVE: The aim of this study was to evaluate the functional level of children
      with congenital and acquired upper limb loss after a rehabilitation program.
      METHODS: This study included a total of 40 children, aged 8 to 17 years with
      upper limb loss. Children were divided into two groups; congenital amputees
      (n=20) and acquired amputees (n=20). The children underwent prosthetic fitting,
      prosthetic training and rehabilitation. The Child Amputee Prosthetics Project -
      Functional Status Inventory (CAPP-FSI) and Prosthetic Upper Extremity Functional
      Index (PUFI) were used at the initial visit to the prosthetic unit without
      prosthesis, 3 weeks after the prosthetic training and 6 months after discharge
      with and without prosthesis. The results with and without the prosthesis were
      compared between the acquired and congenital amputee groups. RESULTS: There were
      significant differences in all tests performed at the baseline, at the 3rd week,
      and at the 6th month without prosthesis and at the 3rd week and at the 6th month
      with prosthesis (p<0.05). The congenital group received higher scores in the CAPP
      FSI and PUFI at the baseline, at the 3rd week and at the 6th month (p<0.05).
      Patients in the congenital group used their prostheses for 8 hours a day and the
      acquired group for 4 to 8 hours. CONCLUSION: Daily prosthesis usage time and the
      child's experience with the prosthesis during daily activities are the
      determining factors for the functional level in upper limb child amputees.
      Functionality may improve based on these factors.

PMID- 22951758
TI  - Effects of unilateral backpack carriage on biomechanics of gait in adolescents: a
      kinematic analysis.
AB  - OBJECTIVE: The aim of this study was to analyze the biomechanical alterations
      during unilateral backpack carriage in adolescents and to compare the kinematic
      parameters of the loaded and unloaded sides. METHODS: Twenty adolescents (mean
      age: 13 +/- 1.2 years) were assessed during walking with no backpack and with a
      backpack on one shoulder. The kinematic parameters of a gait at a self-selected
      speed were analyzed using motion analysis. Specific kinematic peak points were
      compared between asymmetric walking; unloaded, loaded side and mean of unloaded
      walking. RESULTS: Peak ankle dorsal flexion, mean knee varum angle, peak value of
      hip extension and range of pelvic rotation decreased; and knee flexion at initial
      contact, hip adduction angle, mean pelvic anterior tilt and mean pelvic obliquity
      increased on the loaded side relative to the unloaded side and unloaded walking.
      Decreased maximum hip extension during late stance, increased hip adduction,
      elevated pelvis and increased anterior pelvic tilt were seen on the loaded side
      and the pelvis was lowered, ankle dorsal flexion increased and the hip was
      abducted on the unloaded side as a counter effect. CONCLUSION: Both the unloaded
      and loaded sides were affected by asymmetrical backpack carriage. The
      biomechanical alterations seen in asymmetrical backpack carriage may put some
      extra load on the lumbar vertebral joints and altered frontal knee biomechanics
      contribute to low back pain and pathologies in the knee joint.

PMID- 22951759
TI  - Long-segment posterior instrumentation and fusion with freeze-dried allograft in
      congenital scoliosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of long
      segment posterior instrumentation and allograft application in obtaining fusion
      in congenital scoliosis. METHODS: Twenty-one patients with congenital scoliosis
      who were treated with long-segment posterior instrumentation (>6 levels) and
      freeze-dried allograft and followed up for more than 24 months were reviewed. Six
      patients were excluded from the study due to anterior procedures. Fifteen
      patients with congenital scoliosis (13 females, 2 males; mean age: 12.2 +/- 3
      years, range: 7-17 years) were retrospectively reviewed. Mean follow-up time was
      30.9 +/- 9.4 (range: 24 to 48) months. Six patients had laminectomy either due to
      previous posterior surgeries or to address intraspinal pathologies during the
      posterior fusion procedure. Preoperative, postoperative and final follow-up
      anteroposterior and lateral spine X-rays were reviewed. Fusion was graded
      according to the classification reported by Bridwell et al. RESULTS: Two patients
      were graded as 'no fusion' (pseudarthrosis), four patients as 'probably fused',
      and nine patients as 'definitely fused'. The major curve was corrected from an
      average of 68 +/- 18.6 to 39.3 +/- 12.2 degrees (p<0.001). Mean correction lost
      in the major curve was an average of 4.5 +/- 5.2 degrees in the latest follow-up.
      There was significant correction in the compensatory curve (preoperative 37.9 +/-
      13.2 degrees, postoperative 20.2 +/- 6.6 degrees; p=0.001). Preoperative and
      postoperative global thoracic kyphosis were 39.5 +/- 13.3 and 32.3 +/- 7.9
      degrees, respectively (p=0.018). Preoperative and postoperative global lumbar
      lordosis was 36.3 +/- 7.4 and 36.1 +/- 8.9 degrees, respectively (p=0.883).
      Successful fusion was detected in %86.7 of patients in the final follow-up.
      CONCLUSION: The usage of allograft alone to achieve fusion increases the rates of
      pseudarthrosis while additional anterior procedure decreases the pseudarthrosis
      rate in patients with congenital scoliosis that require long-segment posterior
      instrumentation. Further studies should be performed to assess the efficacy of
      the usage of polysegment pedicle screw instrumentation.

PMID- 22951760
TI  - Metatarsal head resurfacing hemiarthroplasty in the treatment of advanced stage
      hallux rigidus: outcomes in the short-term.
AB  - OBJECTIVE: The aim of this study was to evaluate the short-term outcomes of
      metatarsal head metal resurfacing hemiarthroplasty in patients with advanced
      stage hallux rigidus. METHODS: The study included 14 feet (4 left, 10 right) of
      12 patients (10 female, 2 male; mean age: 63 +/- 5; range: 55 to 71 years) who
      underwent metatarsal head metal resurfacing hemiarthroplasty (HemiCAP((r)))
      between 2007 and 2010. Additionally, capsular release and periarticular
      osteophyte debridement were performed. Staging was made according to Coughlin and
      Shurnas' clinical and radiological grading system. Hallux valgus and
      intermetatarsal angles were measured using pre and postoperative standing AP and
      lateral foot views. Clinical assessment was made with first metatarsophalangeal
      joint range of motion, the AOFAS (American Orthopaedic Foot and Ankle Society)
      hallux metatarsophalangeal-interphalangeal scale and satisfaction level. RESULTS:
      Mean follow up was 19.5 (range: 14 to 26) months. Two patients had bilateral
      involvement. According to Coughlin and Shurnas' clinical and radiological grading
      system, nine feet were Stage 3 and five feet were Stage 4. According to the AOFAS
      scale, results of eight feet (57.1%) were excellent, four feet (28.6%) were good
      and two feet (14.3%) were moderate. Mean total AOFAS score increased by 26.2
      points postoperatively (p<0.05). Mean range of motion of the first
      metatarsophalangeal joint improved significantly from a preoperative 22.2 +/- 5.6
      (range: 10 to 28) degrees to a postoperative 56.3 +/- 9.6 degrees (p<0.05). Mean
      hallux valgus angle decreased from a preoperative 14.3 (range: 9 to 17) degrees
      to a postoperative 11.1 (range: 4 to 13) degrees and the mean intermetatarsal
      angle increased from a preoperative 10.5 (range: 8 to 14) degrees to a
      postoperative 10.8 (range: 8 to 15) degrees. Patient satisfaction levels were
      very good in 10 feet (71.4%), good in 3 (21.4%), and moderate in one (7.2%).
      Complications included metatarsalgia aggravated by long walks in one patient and
      hypoesthesia of the great toe in three patients. Push-off power of the great toes
      was measured as 4/5 in three cases, and 5/5 in others. CONCLUSION: Metatarsal
      head metal resurfacing hemiarthroplasty provides high patient satisfaction level
      and good functional outcome in the short-term, in the surgical treatment of
      advanced stage hallux rigidus refractory to conservative treatment options.

PMID- 22951761
TI  - Home-based general versus center-based selective rehabilitation in patients with
      posterior tibial tendon dysfunction.
AB  - OBJECTIVE: The aim of this study was to compare the effect of home-based and
      supervised center-based selective rehabilitation in patients with Grade 1 to 3
      posterior tibial tendon dysfunction (PTTD). METHODS: The study included 49
      subjects diagnosed with PTTD and referred to physiotherapy by an orthopedic
      surgeon. Subjects were randomly assigned into a home-based rehabilitation (21
      cases; mean age: 33.56 +/- 17.59) group or center-based rehabilitation (28 cases;
      mean age: 28.57 +/- 14.74 years). The patients in the home-based rehabilitation
      group followed a home program of cold application, strengthening exercises for
      the posterior tibial and intrinsic muscles, and stretching in the subtalar
      neutral position. The patients in the center-based rehabilitation group followed
      a selective, supervised treatment consisting of the home protocol plus re
      education of the non-functional tibialis posterior, proprioceptive neuromuscular
      facilitation methods, electrical stimulation, joint mobilization and taping
      techniques. Both groups received appropriate orthotics. All subjects were
      assessed before and after treatment for pain, muscle strength, foot function
      index (FFI) scores and specific tests for PTTD. RESULTS: Statistical analysis
      showed significant differences between pre- and post-treatment results for pain,
      first metatarsophalangeal angle, forefoot abduction angle, FFI scores and foot
      and ankle muscle strengths in the center-based group and for the tibialis
      posterior muscle strength in the home-based group (p<0.05). Intergroup
      comparison, however, showed no differences between the groups at the end of the
      treatment program with the exception of posterior tibial muscle strength
      (p<0.05). CONCLUSION: Home- and center-based forms of rehabilitation seem to be
      equally effective in relieving pain and improving functional outcome in patients
      with Grade 1 to 3 PTTD. A patient-selective, supervised program may provide a
      better improvement in tibialis posterior strength than home-based rehabilitation.

PMID- 22951762
TI  - Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff
      repair in rats: an in vivo experimental study.
AB  - OBJECTIVE: The purpose of this experimental study was to analyze the effects of
      local autologous platelet-rich plasma (PRP) injection on tendon-to-bone healing
      in a rotator cuff repair model in rats. METHODS: Rotator cuff injury was created
      in 68 left shoulders of rats. PRP was obtained from the blood of an additional 15
      rats. The 68 rats were divided into 4 groups with 17 rats in each group; PRP
      group (Week 2), control group (Week 2), PRP group (Week 4), and control group
      (Week 4). Platelet-rich plasma or saline was injected to the repair area
      intraoperatively. Rats were sacrificed 2 and 4 weeks after the surgery.
      Histological analysis using a semiquantitative scoring was performed on 7 rats
      per group. Tendon integrity and increases in vascularity and inflammatory cells
      and the degree of new bone formation were evaluated and compared between the
      groups. The remaining tendons (n=10) were mechanically tested. RESULTS: Degree of
      inflammation and vascularity were less in the study group at both time intervals
      (p<0.05). Tendon continuity was better in the study group at 2 weeks (p<0.05).
      Obvious new bone formation was detected in the control group at 4 weeks (p<0.05).
      Biomechanically, platelet-rich plasma-treated specimens were stronger at 2 weeks
      (p<0.05). CONCLUSION: Local autologous PRP injection may have beneficial effects
      on initial rotator cuff tendon-to-bone healing and enhance initial tendon-to-bone
      healing remodeling. This may represent a clinically important improvement in
      rotator cuff repair.

PMID- 22951763
TI  - Carotid sinus hypersensitivity due to shoulder sling pressure after arthroscopic
      rotator cuff repair: a case report.
AB  - The beach chair position is one of the most commonly used positions in
      arthroscopic shoulder surgery because of its anatomical nature and easy
      modifiability to open surgery. Despite these advantages, thromboembolic and
      neurologic complications have been reported. We report a case of carotid sinus
      hypersensitivity due to shoulder sling pressure after arthroscopic shoulder
      surgery.

PMID- 22951764
TI  - Bilateral femoral neck stress fracture following bilateral total knee
      arthroplasty: a case report.
AB  - In the treatment of degenerative knee arthritis, total knee arthroplasty is a
      commonly performed surgery. After knee replacement, stress fractures at lower
      extremity may rarely occur due to changes in lower extremity alignment and
      biomechanical axis. We report an 82-year-old woman with a bilateral femoral neck
      stress fracture 3 years after bilateral total knee replacement. Physicians should
      be aware of this rare complication and these fractures should be treated without
      any surgical delay.

PMID- 22951765
TI  - Cystic transphyseal bone tuberculosis: a report of two cases.
AB  - We present two cases of tuberculosis osteomyelitis mimicking subacute
      osteomyelitis and treated without extensive debridement. Tuberculous
      osteomyelitis should be considered in the differential diagnosis of proximal
      tibial infections in children and early diagnosis and treatment is possible
      without extensive debridement.

PMID- 22951766
TI  - Para-articular extraskeletal osteochondroma: the nomenclature dilemma and
      difficulties in differential diagnosis.

PMID- 22951768
TI  - The male victim of sexual assault.
AB  - Under-reporting by male victims is more pronounced than for females victims, and
      so male victims remain a rarity for most sexual assault aftercare service
      providers. In this chapter, I present a review of forensic medical and psycho
      social literature on male-on-male rape and sexual assault. Where appropriate,
      comparison is made with female victims, as that is the context with which most
      aftercare service providers are familiar. The following aspects are covered:
      prevalence; definitions; social perceptions of perpetrators and victims of sexual
      assault on males; characteristics of victims and assaults; physiological and
      psychological responses; and implications for forensic medical investigation.

PMID- 22951769
TI  - Demographics of infertility and management of unexplained infertility.
AB  - The cause of infertility is unexplained in about 22-28% of all infertile couples.
      The prognosis for spontaneous pregnancy in such couples is better than in those
      with diagnosed causes of infertility. Traditional treatment options in this group
      have included expectant management, clomifene citrate, intrauterine insemination
      with (super ovulation plus intrauterine insemination) or without (intrauterine
      insemination) super ovulation and in-vitro fertilisation. Despite being more
      expensive, empirical clomifene and intrauterine insemination in an unstimulated
      cycle do not improve the chances of live birth compared with expectant
      management. Although unlikely to be more effective than no treatment in couples
      with a reasonably good prognosis, super ovulation plus intrauterine insemination
      has been shown to be more effective than intrauterine insemination. Any potential
      advantage of super ovulation plus intrauterine insemination has to be balanced
      against the relatively high risk of iatrogenic multiple pregnancy. In-vitro
      fertilisation remains the treatment of choice in longstanding unresolved
      infertility and, when coupled with the use of elective single embryo transfer,
      can minimise the risk of multiple pregnancies. Data from randomised trials
      confirming the superiority of in-vitro fertilisation over expectant management is
      limited.

PMID- 22951770
TI  - [What is typical in atypical Parkinsonian syndromes?].

PMID- 22951771
TI  - [Schizophrenic psychoses with bipolar course--implications for nosology and
      treatment].
AB  - Based on a description of the psychopathological symptoms and clinical course of
      three patients, the diagnostic classification of schizophrenia, schizoaffective
      disorder and bipolar affective disorder is discussed. The reported cases are
      characterised by a rapid change of cognition, affect and psychomotor domain with
      fluctuations in two opposite directions and an incomplete remission of symptoms
      between acute episodes of illness. Such cases are not adequately represented in
      the current diagnostic systems ICD-10 and DSM-IV. This renders both the
      diagnostic classification and the development of evidence-based treatment
      guidelines more difficult. In accordance with the historical concepts of Emil
      Kraepelin and Kurt Schneider, the reported patients can be considered to suffer
      from a subtype of schizophrenia with bipolar course. The identification of such
      psychopathological course types could help to develop more concise and
      individualised treatment guidelines. In contrast, the characterisation of the
      reported cases using dimensional models seems doubtful.

PMID- 22951773
TI  - [Mechanical thrombectomy for the treatment of acute stroke--an update].

PMID- 22951772
TI  - [Meningoencephalitis and ventricular arrhythmia caused by yersiniosis].
AB  - We report on a 19-year-old patient without any immunodeficiency and without a
      history of significant diseases in whom two seizure attacks as symptoms of
      meningoencephalitis occurred after he had suffered from abdominal symptoms for a
      week. Later, we could observe frequent polymorphic ventricular extrasystoles. A
      massive production of anti-Yersinia IgM, IgG and IgA as a sign of an acute
      infection could be found, although we were not able to detect the microbe itself
      with culturing methods. After targetted antibiotic treatment, the patient fully
      recovered within two weeks and could be discharged from hospital without clinical
      abnormalities and an almost normalised cell count in the cerebrospinal fluid.
      Possible ways of infection are mice which the patient kept as pets and his work
      in the sewer system. The present case reminds us to think of uncommon infectious
      agents even in young patients without a predisposition but unusual symptoms
      and/or potentially relevant anamnestic data.

PMID- 22951775
TI  - [Autonomic regulation of the heart rate in infants with cerebral hypoxia-ischemia
      of I-II degrees].
AB  - Characteristics of psychomotor development and neurohumoral regulation of the
      cardiac heart rate in 34 infants with cerebral hypoxia-ischemia of I-II degrees,
      depending on the leading syndrome, have been studied. Individual-typological
      features of psychomotor development of infants with perinatal transient
      posthypoxic-ischemic encephalopathy, depending on central regulatory mechanisms,
      are defined. The data on adaptation mechanisms and sequence of their involvement
      into the process of the formation of motor functions in infants are presented.

PMID- 22951776
TI  - [A clinical test for diagnosis of myasthenic ptosis].
AB  - A clinical test for diagnosis of ptosis in myasthenia is described. We studied
      the effect of antiorthostatic posture with head-down position on the degree of
      ptosis in myasthenia, ocular myopathy of von Graefe, lesions of the oculomotor
      nerve and pseudoptosis. The antiorthostatic posture significantly (p<0,05)
      decreased the degree of ptosis only in patients with myasthenia The degree of
      ptosis remained unchanged in myopathy of von Graefe, lesions of the oculomotor
      nerve and pseudoptosis.

PMID- 22951777
TI  - [Characteristics of the pre-manifest stage in young patients with the first
      episode endogenous psychosis].
AB  - A retrospective study of pre-manifest personality traits in 120 young patients
      (16-25 years old) identified the clinical heterogeneity of the period preceding
      the first episode of juvenile endogenous attack-like psychosis. Depending on the
      degree of personality abnormalities, patients were stratified into 3 groups as
      having accentuated personality traits, personality disorders (psychopathy) or
      pseudopsychopathy, the latter divided into deficit and degenerative subgroups.
      Correlations between the degree of personality abnormality and the type of
      manifest episode and its nosological status were found.

PMID- 22951778
TI  - [Use of pregabalin and sertraline in complex treatment of patients with partial
      epilepsy comorbid with depressive and anxiety disorders].
AB  - Objective of this study was evaluation therapeutic efficacy and adverse effects
      of the combined treatment in patients with partial epilepsy comorbid with
      depressive and anxiety disorders. Patients were treated with antiepileptic drugs
      (AED) as monotherapy before and during the investigation. Patients of group 1 (42
      cases) were administrated sertraline (SER) 100 mg per day in combination with
      pregabalin (PGB) 300 mg per day in addition to basic AED. Patients of group 2 (41
      cases) were treated with SER 100 mg per day in addition to basic AED. The
      duration of the investigation has made 6 months. In this study several
      characteristics had been evaluated in each group: seizure frequency, severity of
      depressive and anxiety disorders, adverse effects of the drugs administrated.
      Moreover, dynamics of types of attitude to the disease were investigated under
      the drugs administration in each group. SER and PGB demonstrated high efficacy
      and safety in treatment partial epilepsy comorbid with depressive and anxiety
      disorders. PGB must be recommended in adjunctive therapy of anxiety disorders in
      patients with partial epilepsy.

PMID- 22951779
TI  - [Valdoxan (agomelatine) in combined therapy of moderate and severe non-psychotic
      depressions].
AB  - According to data received from the study VREMYA, the combined therapy of
      moderate and severe non-psychotic depressions with Valdoxane and antidepressants
      of other pharmacological groups is effective and doesn't cause serious adverse
      events. These findings suggested using the indicated combination of
      antidepressants in treatment of resistant affective disorders.

PMID- 22951780
TI  - [Demyelinating polyneuropathies in patients with diabetes mellitus and chronic
      alcoholic intoxication].
AB  - Frequency and nosological attribution of demyelinating polyneuropathies in
      patients with diabetes mellitus and alcoholism were determined. Eighty-six
      inpatients with alcoholic (n=46) and diabetic (n=40) polyneuropathy were examined
      clinically and using electroneuromyography (ENMG). A demyelinating pathogenetic
      variant was identified by clinical and ENMG data in 27 (31%) patients. Nine
      patients (33%) had dysimmune polyneuropathies (acute and chronic inflammatory
      demyelinating polyneuropathy). Polyneuropathies were specified as toxic/metabolic
      with the prevalence of a demyelinating component within the main disease in 18
      (67%) patients. Clinical and ENMG-signs of the demyelinating variant of alcoholic
      and diabetic neuropathy are presented. The efficacy of the antioxidant berlition
      was shown for toxic/metabolic polyneuropathies while the addition of immune
      modulators was needed for treatment of dysimmune polyneuropathy.

PMID- 22951781
TI  - [The effect of neurotrophic treatment on the activation of reparative processes
      in patients with acute traumatic brain injury].
AB  - The complex study of cognitive and emotional status, levels of serum serotonin
      and brain-derived neurotrophic factor (BDNF) were performed in 72 patients with
      acute traumatic brain injury, with a special focus on middle brain injuries
      (MBI), treated with Cerebrolysin. The neurological and cognitive impairment, mild
      state anxiety and depression and increased levels of humoral serotonin, which
      depends on the severity of the injury, were identified in patients with MBI
      before treatment. After the treatment, there were the decrease in the severity of
      neurological symptoms and a significant positive dynamics on the FAB scale as
      well as the increase in blood BDNF and serotonin levels. It has been concluded
      that using cerebrolysin in complex treatment of acute MBI promotes activation of
      neurotrophic processes and improves outcomes of closed craniocerebral injury.

PMID- 22951782
TI  - [A combined preparation stalevo in Parkinson's disease: a 5-year experience of
      continuous dopaminergic stimulation].
AB  - Levodopa remains a 'gold standard' for the treatment of patients with Parkinson's
      disease (PD), but its chronic use is accompanied by fluctuations of symptoms and
      dyskinesias related to unfavorable pharmacokinetics of levodopa and progressing
      loss of the nigrostriatal neurons. Prescribing inhibitors of catechol-O-methyl
      transferase (enzyme of dopamine metabolism), entacapone or tolcapone, is a
      perspective approach to the correction of the above-mentioned complications. We
      followed up 402 patients with PD who received long-term therapy with a combined
      preparation Stalevo (levodopa/carbidopa/entacapone) for 2-5 years (2.9 +/- 0.9
      years). The high (92.8%) compliancy and good tolerance of the drug in patients
      with PD was shown. Stalevo leads to the stabilization of the response to
      levodopa, improvement of patients' functional capacities, increase in their
      everyday activity, and improvement of quality of life. Stalevo may be regarded as
      a preparation of choice in the treatment of motor complications in elderly
      patients, correction of night symptoms of PD and in a number of other clinical
      situations arising in hospital and outpatient practice.

PMID- 22951783
TI  - [Results of a comparative clinical trial of the Russian Beta - interferon-1b
      bioanalogue (infibeta)].
AB  - Results of annual comparative clinical research of the Russian biosimilar of beta
      IFN - 1v at 122 patients with multiple sclerosis are presented. There were
      positive dynamics on EDSS scores in both groups (in the main group and group of
      control) in a year of treatment. There were positive dynamics in frequency of
      relapses in the main group (with 1.5 to 0.4 in a year) and in group of control
      (with 1.4 to 0.37 in a year). Positive dynamics according to MRI was also fixed
      in both groups. In both groups, good tolerability of the treatment was noted.
      This research didn't reveal essential distinctions on efficiency and safety
      parameters in both groups.

PMID- 22951784
TI  - [Higher mental functions and cognitive auditory event-related potentials
      impairment in liquidators of Chernobyl accident].
AB  - An integrated neuropsychological study and analysis of cognitive auditory event
      related potentials (ERP) using the three-stimulus oddball paradigm was performed
      in ten subjects who participated in the liquidation of Chernobyl accident and ten
      healthy subjects. Impairment of higher mental functions, including aspontaneity,
      fatigability, a decrease in the auditory-verbal and visual memories, and higher
      motor function deficiency was shown in liquidators. A decrease of amplitude in
      all components of ERP (N1, N2 and P3) was found in liquidators for all stimuli in
      both experimental situations (audition of all stimuli and counting of deviant
      stimuli) compared to healthy subjects. The latent period (LP) of ERP in
      liquidators was decreased for N1 and N2 components and increased for P3. The
      largest between-group differences in the LP were revealed in the frontal areas
      for N1 and P3 in the left hemisphere and for N2 - in the right one. The
      correlation analysis between the ERP and a neuropsychological study had shown
      that changes in the LP of N1 are correlated to the impairment of short-term
      memory and pose praxis of the right hand while changes in the N2 were correlated
      to the impairment of long-term memory and pose praxis of the left hand. The
      changes in LP of P3 were correlated to complex cognitive processing disorders.
      Thus, the complex study identified the deceleration of perception, processing,
      and analysis of information combined with the weakened inhibition and
      "uneconomical" type of reactivity which led to the impairment of higher mental
      functions in liquidators compared to healthy subjects of the same age. The
      changes found in liquidators are similar to those observed in elderly people and
      support the hypotheses on accelerated brain ageing caused by low dose
      irradiation.

PMID- 22951785
TI  - [Medical - rehabilitation schizophrenic patients and their families' potential].

PMID- 22951786
TI  - [Disorders of nervous system at patients with diabetes mellitus].

PMID- 22951787
TI  - [Focal dystonias and their treatment with dysport (botulinum toxin type A)].

PMID- 22951788
TI  - [Low back pain].

PMID- 22951789
TI  - [Autonomic dysfunction as additive risk factor of epilepsy].

PMID- 22951790
TI  - [Injectable extended-release naltrexone for opioid dependence: a double-blind,
      placebo-controlled, multicentre randomized trial].
AB  - We aimed to assess the efficacy and safety of an injectable, once monthly
      extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for
      treatment of patients with opioid dependence after detoxification. Two hundreds
      and fifty patients with opioid dependence were enrolled into the double-blind,
      placebo-controlled, randomized, 24-week trial. Patients aged 18 years or over who
      had inpatient detoxification and 7 days or more off all opioids were enrolled at
      13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg
      XR-NTX (n=124) or placebo (n=126). Participants also received 12 biweekly
      counseling sessions. The primary endpoint was the response profile for confirmed
      abstinence during weeks 5-24 assessed by urine drug tests and self report of non
      use. Secondary endpoints were self-reported opioid- free days, opioid craving
      scores, number of days of retention, and relapse to physiological opioid
      dependence. IN CONCLUSION: XR-NTX represents a new treatment option. XR-NTX in
      conjunction with psychosocial treatment was more effective for treatment of
      opioid dependence compare to psychosocial support and placebo.

PMID- 22951791
TI  - [Comorbid neurotic disorders in opioid-dependent patients].
AB  - Necessity of distinguishing between psychopathology of opioid dependence itself
      and co-occurred neurotic (ICD-10 item F4) disorders is caused by the need to
      choose an adequate therapy. The prevalence and types of comorbid neurotic
      disorders among opioid-dependent patients in sustained full and partial remission
      are described.

PMID- 22951792
TI  - [Comorbidity of opioid addiction and alcoholism in patients of young age:
      clinical variants of the double diagnosis].
AB  - A study included 115 male patients with opioid addiction, aged from 17 to 27
      years. Comorbidity of opioid addiction and alcoholism in patients of young age
      was represented by two main variants distinguishing between primary dependence on
      opioid or alcohol. In the first variant, additional variants of vicarious
      alcoholization and replacement of addiction form were singled out. In the second
      case, alcoholism preceded opioid addiction that developed as a form of
      polyaddiction and the formation of preliminary (primary) alcoholism was
      considered as a protracted stage of searching narcotism with the transition from
      alcoholism to opioid addiction. Stages and differential criteria of the variants
      of double disorders are described.

PMID- 22951793
TI  - [Cognitive impairment in patients with opioid addiction].
AB  - The authors present the results of a study on cognitive dysfunction in 77
      patients with opioid addiction. Cognitive functions were assessed with a battery
      of neuropsychological tests after stopping the syndrome of opiate withdrawal.
      Significant impairment of memory, memorization, attention, generalization and
      abstract thinking were identified in the majority of patients.

PMID- 22951794
TI  - [Functional features of the nervous system in adolescents using inhalants].
AB  - The study of features of the nervous system functioning with a complex of
      physiological methods in adolescents using inhalants has detected the significant
      functional asymmetry of hemispheres, imbalance and lability of nervous processes,
      domination of medium-weak and weak response of the nervous system, low speed of
      response, poor dynamics of nervous processes, disturbance of regulation and
      control of psychic activity. It has been proposed to use assessment of the
      functional status of the nervous system during inhalant in medical-diagnostic
      practice for development of individual correction programs.

PMID- 22951795
TI  - [Antidepressants in the treatment of alcoholism].
AB  - Alcoholism is characterized by a high frequency of comorbid depression, and both
      diseases have a mutual negative impact. The frequent comorbidity of alcoholism
      and depression (as well as disorders related to anxiety) serves as the basis for
      use of antidepressants for individuals suffering from alcohol dependence. Among
      the drugs of choice in the treatment of alcohol dependence complicated by
      depression and anxiety disorders, is escitalopram.

PMID- 22951796
TI  - [Cardiac rhythm disorders and arterial hypertension in treatment-compliant
      patients with alcoholic dependence: features of the clinical course and therapy].
AB  - Features of dynamics of arterial hypertension and rhythm disorders within 3 years
      after the termination of alcohol intake were studied. The study included 260
      patients with alcoholic dependence at the age from 22 to 74 years (mean age 46+/
      6.6 years). The functional state of the cardiovascular system was evaluated. It
      has been shown that within 1 month after the termination of alcohol intake, 73.1%
      of patients develop arterial hypertension that needs treatment. Cardiac rhythm
      disorders were registered in 23.1% of cases. Antiarrhythmic drugs are
      recommended, in at least 83.1% cases, to patients having the combination of
      arterial hypertension and paroxismal ventricular rhythm disorders in the endpoint
      of the study. Efficacy of hypotensive and antiarrhytmic drugs is analyzed.

PMID- 22951797
TI  - [The influence of suicidal tendencies on non-suicidal autoaggressive behavior,
      psychological phenomena and addictive disorders in men with alcoholic
      dependence].
AB  - The effect of suicidal activity on the auto-aggressive behavior and addictive
      behavior as well as on psychological traits has been studied in 125 men with
      alcoholic dependence. The presence of suicidal tendencies sharply increases the
      probability of various forms of non-suicidal auto-destructive behavior. This
      category of patients has specific personality-psychological features and the
      peculiar clinical presentation of the prior addictive disease.

PMID- 22951798
TI  - [Hepatoprotectors in addictive medicine].

PMID- 22951799
TI  - [Social-demographic and behavioral characteristics of drug users and evaluation
      of their population in the cities of the North-Western Federal Region].

PMID- 22951800
TI  - [Organization of drug addiction aid for chronic alcoholic patients in the Penza
      Region].

PMID- 22951801
TI  - [The study of efficacy of the psychotherapy program for relatives of patients
      with opioid addiction].
AB  - Results of a randomized controlled trial on the efficacy of psychotherapy program
      for treatment of co-dependence in relatives of patients with opioid addiction are
      presented. The study included 142 people, 96 male and 46 female, mean age 26.3+/
      2.1 years. Efficacy of treatment was estimated by the portion of patients in
      remission and psychometric data. A positive effect of the program on the
      stabilization of remission of drug addiction, recovery of social functioning and
      strengthening of the motivation to stay clean was demonstrated.

PMID- 22951802
TI  - [To a question of effective social anti-drug advertising].

PMID- 22951803
TI  - [Prevalence of tobacco smoking in addiction medicine specialists in Moscow].
AB  - According to the questionnaire results, high smoking rates among medical doctors
      working in Moscow drug-addiction out-patient clinics were identified: 78% of
      males and 42% of females smoke or used to smoke. The long duration and high
      intensity of smoking were noted. Interestingly, a large number of smoking doctors
      (36% of men and 43% of women) do not want to quit smoking. Smoking addiction
      medicine specialists pay far less attention to prevention and treatment of
      tobacco dependence in their patients.

PMID- 22951804
TI  - Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian
      failure.
AB  - BACKGROUND: WNT4 and SF1 genes play an important role in ovarian development.
      They constitute coherent candidate genes associated with premature ovarian
      failure (POF) pathogenesis. METHODS: We sequenced the coding region of WNT4 and
      SF1 in 55 Tunisian women with POF and 100 healthy controls. RESULTS: We
      identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a
      substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG-GCG) missense
      mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology.
      However, a positive association of SF1 Gly146Ala polymorphism was noted.
      Gly146Ala minor allele frequency was significantly higher (p=0.029) in POF
      patients versus controls and Ala allele containing genotypes (p=0.005) were
      positively associated with POF pathology. The carriage of 146Ala allele was also
      associated with a significant reduction in estradiol plasma levels. CONCLUSIONS:
      SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the
      Tunisian population likely by reducing estradiol levels.

PMID- 22951805
TI  - Species-specific size expansion and molecular evolution of the oleosins in
      angiosperms.
AB  - Oleosins are hydrophobic plant proteins thought to be important for the formation
      of oil bodies, which supply energy for seed germination and subsequent seedling
      growth. To better understand the evolutionary history and diversity of the
      oleosin gene family in plants, especially angiosperms, we systematically
      investigated the molecular evolution of this family using eight representative
      angiosperm species. A total of 73 oleosin members were identified, with six
      members in each of four monocot species and a greater but variable number in the
      four eudicots. A phylogenetic analysis revealed that the angiosperm oleosin genes
      belonged to three monophyletic lineages. Species-specific gene duplications,
      caused mainly by segmental duplication, led to the great expansion of oleosin
      genes and occurred frequently in eudicots after the monocot-eudicot divergence.
      Functional divergence analyses indicate that significant amino acid site-specific
      selective constraints acted on the different clades of oleosins. Adaptive
      evolution analyses demonstrate that oleosin genes were subject to strong
      purifying selection after their species-specific duplications and that rapid
      evolution occurred with a high degree of evolutionary dynamics in the pollen
      specific oleosin genes. In conclusion, this study serves as a foundation for
      genome-wide analyses of the oleosins. These findings provide insight into the
      function and evolution of this gene family in angiosperms and pave the way for
      studies in other plants.

PMID- 22951806
TI  - Genetic polymorphisms in the DNA repair gene XRCC1 and susceptibility to glioma
      in a Han population in northeastern China: a case-control study.
AB  - BACKGROUND: Several single nucleotide polymorphisms (SNPs) in the X-ray cross
      complementing group 1 (XRCC1) gene have been shown to influence DNA repair and to
      modify cancer susceptibility. To investigate the role of these loci further, we
      examined the association of three XRCC1 polymorphisms with the risk of gliomas in
      a Han population in northeastern China. METHODS: Using a PCR-RFLP method, XRCC1
      Arg194Trp, Arg280His and Arg399Gln were genotyped in 624 glioma patients and 580
      healthy controls. RESULTS: Significant differences in the distribution of the
      Arg399Gln allele were detected between glioma patients and healthy controls by a
      logistic regression analysis (OR=1.35, 95%CI 1.17-1.68, P=0.001). Our data also
      revealed that the Arg399Gln variant (allele A) carriers had an increased glioma
      risk compared to the wild-type (allele G) homozygous carriers (OR=1.40, 95%CI
      1.12-1.76, P=0.003). CONCLUSIONS: These results suggest that the XRCC1 Arg399Gln
      might influence the risk of developing glioma in a Han population in northeastern
      Chinese.

PMID- 22951807
TI  - Actin capping proteins, CapZ (beta-actinin) and tropomodulin in amphioxus
      striated muscle.
AB  - CapZ (beta-actinin) and tropomodulin (Tmod) are capping proteins involved in the
      maintenance of thin filaments in vertebrate skeletal muscles. In this study, we
      focused on amphioxus, the most primitive chordate. We searched for CapZ and Tmod
      genes in the amphioxus genome and determined their primary structures. Amphioxus
      possess one CapZalpha gene (CAPZA) and one CapZbeta gene (CAPZB), and the
      transcripts of these genes were found to be 67%-85% identical to those of human
      CapZ genes. On the other hand, amphioxus contain one Tmod gene (TMOD), and the
      product of this gene has an identity of approximately 50% with human Tmod genes 1
      4. However, helix 2 of amphioxus Tmod, which is involved in protein-binding to
      tropomyosin, was highly conserved with approximately 74% identity to human Tmod
      genes. Western blotting indicated the presence of CapZ and Tmod in the striated
      muscle of amphioxus. These results suggest that unlike most of vertebrates, such
      as fish, amphibian, bird, and mammal, CapZ from amphioxus striated muscle is
      derived from two genes CAPZA and CAPZB, and Tmod is derived from one TMOD gene.

PMID- 22951808
TI  - Design and analysis of multiple diseases genome-wide association studies without
      controls.
AB  - In genome-wide association studies (GWAS), multiple diseases with shared controls
      is one of the case-control study designs. If data obtained from these studies are
      appropriately analyzed, this design can have several advantages such as improving
      statistical power in detecting associations and reducing the time and cost in the
      data collection process. In this paper, we propose a study design for GWAS which
      involves multiple diseases but without controls. We also propose corresponding
      statistical data analysis strategy for GWAS with multiple diseases but no
      controls. Through a simulation study, we show that the statistical association
      test with the proposed study design is more powerful than the test with single
      disease sharing common controls, and it has comparable power to the overall test
      based on the whole dataset including the controls. We also apply the proposed
      method to a real GWAS dataset to illustrate the methodologies and the advantages
      of the proposed design. Some possible limitations of this study design and
      testing method and their solutions are also discussed. Our findings indicate that
      the proposed study design and statistical analysis strategy could be more
      efficient than the usual case-control GWAS as well as those with shared controls.

PMID- 22951809
TI  - Proteome analysis of gut and salivary gland proteins of fifth-instar nymph and
      adults of the sunn pest, Eurygaster integriceps.
AB  - In the digestive system of the sunn pest, Eurygaster integriceps Puton
      (Hemiptera: Scutelleridae), the salivary gland has a key role in extra oral
      digestion and the gut is the main site for digestion of food. In this study,
      proteomics was used to study the role of proteins involved in digestion. The
      amount of feeding on wheat grain by adult insects increased by comparison to
      fifth-instar nymphs. Proteins of the gut and salivary gland in adults and fifth
      instar nymphs were analyzed 1 day after feeding. The proteins related to
      digestion, metabolism, and defense against toxins were accumulated in the gut of
      adult insects. Three plant proteins including serpin, dehydroascorbate reductase,
      and beta-amylase were accumulated in guts of adults. In the salivary gland,
      phospholipase A2 and arginine kinase were increased in adults. Heat shock protein
      70 increased in the gut of fifth-instar nymphs. Proteomic analysis revealed that
      most of changed proteins in digestive system of sunn pest were increased in
      adults. This study provided more targets derived from gut and salivary gland for
      pest management.

PMID- 22951810
TI  - Tobacco control and trade policy: proactive strategies for integrating policy
      norms.
AB  - Palpable tension continues at the intersection of tobacco control and trade
      policy. Through consideration of four major tobacco control-related trade
      disputes, we suggest how to empower public health proponents in the face of
      entrenched economic policymaking norms. We argue that a more effective pro
      tobacco control message should: (a) seek to be broadly consistent with core
      principles of the world trading system, (b) boldly assert countries'
      international commitments to the Framework Convention on Tobacco Control, (c)
      marshal deep scientific evidence, and (d) come from a broad range of actors,
      including from low- and middle-income countries as well as from other trade
      policy community members.

PMID- 22951811
TI  - The first asymmetric ring-expansion carbonylation of meso-epoxides.
AB  - The first asymmetric ring-expansion carbonylation of meso-epoxides to beta
      lactones is reported. Two structurally diverse chiral Cr(III) chloro complexes in
      conjunction with Co(2)(CO)(8) were shown to be competent catalytic systems for
      this transformation, displaying significant levels of asymmetric induction of up
      to 56% ee.

PMID- 22951812
TI  - Perception of lung function, adherence to inhaled corticosteroids, and the role
      of peak expiratory flow feedback in paediatric asthma.

PMID- 22951813
TI  - Pain outcomes in patients with advanced breast cancer and bone metastases:
      results from a randomized, double-blind study of denosumab and zoledronic acid.
AB  - BACKGROUND: In this study, the authors evaluated the effect of denosumab versus
      zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone
      metastases. METHODS: The prevention of pain, reduction in pain interference with
      daily life activities, and the proportion of patients requiring strong opioid
      analgesics were assessed in a randomized, double-blind, double-dummy phase 3
      study comparing denosumab with ZA for preventing skeletal-related events in 2046
      patients who had breast cancer and bone metastases. Patients completed the Brief
      Pain Inventory-Short Form at baseline and monthly thereafter. RESULTS: Fewer
      patients who received denosumab reported a clinically meaningful worsening of
      pain severity (>=2-point increase) from baseline compared with patients who
      received ZA, and a trend was observed toward delayed time to pain worsening with
      denosumab versus ZA (denosumab, 8.5 months; ZA, 7.4 months; P = .08). In patients
      who had no/mild pain at baseline, a 4-month delay in progression to
      moderate/severe pain was observed with denosumab compared with ZA (9.7 months vs
      5.8 months; P = .002). Denosumab delayed the time to increased pain interference
      by approximately 1 month compared with ZA (denosumab, 16.0 months; ZA, 14.9
      months; P = .09). The time to pain improvement (P = .72) and the time to
      decreased pain interference (P = .92) were similar between the groups. Fewer
      denosumab-treated patients reported increased analgesic use from no/low use at
      baseline to strong opioid use. CONCLUSIONS: Denosumab demonstrated improved pain
      prevention and comparable pain palliation compared with ZA. In addition, fewer
      denosumab-treated patients shifted to strong opioid analgesic use.

PMID- 22951814
TI  - The cardiovascular risk of azithromycin was increased in a large observational
      cohort study, contradicting findings from prior randomised trials.

PMID- 22951815
TI  - A small proportion of people with dementia and neuropsychiatric symptoms
      experience clinically significant worsening when antidepressants are
      discontinued.

PMID- 22951816
TI  - Intramolecular alkoxycyanation and alkoxyacylation reactions: new types of alkene
      difunctionalizations for the construction of oxygen heterocycles.

PMID- 22951817
TI  - Revisiting sesquiterpene biosynthetic pathways leading to santalene and its
      analogues: a comprehensive mechanistic study.
AB  - Santalene and bergamotene are the major olefinic sesquiterpenes responsible for
      the fragrance of sandalwood oil. Herein we report the details of density
      functional theory investigations on the biosynthetic pathway of this important
      class of terpenes. The mechanistic study has been found to be effective toward
      gaining significant new insight into different possibilities for the formation of
      the key intermediates involved in santalene and bergamotene biosynthesis. The
      stereoelectronic features of the transition states and intermediates for (i) ring
      closure of the initial bisabolyl cation, and (ii) skeletal rearrangements in the
      ensuing bicyclic carbocationic intermediates leading to (-)-epi-beta-santalene, (
      )-beta-santalene, (-)-alpha-santalene, (+)-epi-beta-santalene, exo-beta
      bergamotene, endo-beta-bergamotene, exo-alpha-bergamotene, and endo-alpha
      bergamotene are presented. Interesting structural features pertaining to certain
      new carbocationic intermediates (such as b) resulting from the ring closure of
      bisabolyl cation are discussed. Extensive conformational sampling of all key
      intermediates along the biosynthetic pathway offered new insight into the role of
      the isoprenyl side chain conformation in the formation of santalene and its
      analogues. Although the major bicyclic products in Santalum album appear to arise
      from the right or left handed helical form of farnesyl pyrophosphate (FPP),
      different alternatives for their formation are found to be energetically
      feasible. The interconversion of the exo and endo isomers of bisabolyl cation and
      a likely epimerization, both with interesting mechanistic implications, are
      presented. The exo to endo conversion is identified to be energetically more
      favorable than another pathway emanating from the left handed helical FPP. The
      role of pyrophosphate (OPP(-)) in the penultimate deprotonation step leading to
      olefinic sesquiterpenes is also examined.

PMID- 22951820
TI  - Cochlear implant programs: balancing clinical and financial sustainability.
AB  - OBJECTIVES/HYPOTHESIS: In 2006, a tertiary academic medical center's adult and
      pediatric cochlear implant program was closed due to financial losses. Using
      business practices known as supply chain and revenue management, the objective
      was to establish a new cochlear implant program that was financially viable.
      STUDY DESIGN: Retrospective cohort study using a nonequivalent historical
      comparison group design. METHODS: Using available financial data from the period
      of 1999 to 2006, cost and revenue figures were estimated, and a business plan
      developed using supply chain and revenue management principles to re-establish
      the cochlear implant program in 2007. Actual cost and revenue data from 2007 to
      2011, the current program, were assessed for current financial performance and
      compared to the historical data. RESULTS: In comparing the period of 1999 to 2006
      to the period of 2007 to 2011, the net loss per implanted patient went from
      $22,365 to $976. Profitable gross and net margins were achieved for all payers
      except Medicaid, for which the loss per case remained unchanged. This per case
      loss may change with receipt of pending Medicaid Upper Payment Limit supplemental
      payments. CONCLUSIONS: Use of supply chain and revenue management principles
      markedly improved the financial performance of the re-established cochlear
      implant program. With improved cost and revenue outcomes, the overall negative
      net margin was reduced. Physicians who learn and use supply chain and revenue
      management methods can work to ensure that their patients will have continued
      access to cochlear implant surgery, and are applicable to any clinical services
      or procedures that must meet the challenge of achieving financial sustainability.

PMID- 22951821
TI  - Zinc finger antiviral protein inhibits murine gammaherpesvirus 68 M2 expression
      and regulates viral latency in cultured cells.
AB  - Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits
      the replication of certain viruses by binding to specific viral mRNAs and
      repressing mRNA expression. Here we report that ZAP inhibits expression of murine
      gammaherpesvirus 68 (MHV-68) M2, which plays important roles in establishment and
      maintenance of viral latency. Downregulation of endogenous ZAP in cells harboring
      latent MHV-68 promoted lytic replication of the virus. These results suggest that
      ZAP inhibits M2 expression and regulates the maintenance of MHV-68 latency.

PMID- 22951822
TI  - In vitro quantification of the relative packaging efficiencies of single-stranded
      RNA molecules by viral capsid protein.
AB  - While most T=3 single-stranded RNA (ssRNA) viruses package in vivo about 3,000
      nucleotides (nt), in vitro experiments have demonstrated that a broad range of
      RNA lengths can be packaged. Under the right solution conditions, for example,
      cowpea chlorotic mottle virus (CCMV) capsid protein (CP) has been shown to
      package RNA molecules whose lengths range from 100 to 10,000 nt. Furthermore, in
      each case it can package the RNA completely, as long as the mass ratio of CP to
      nucleic acid in the assembly mixture is 6:1 or higher. Yet the packaging
      efficiencies of the RNAs can differ widely, as we demonstrate by measurements in
      which two RNAs compete head-to-head for a limited amount of CP. We show that the
      relative efficiency depends nonmonotonically on the RNA length, with 3,200 nt
      being optimum for packaging by the T=3 capsids preferred by CCMV CP. When two
      RNAs of the same length-and hence the same charge-compete for CP, differences in
      packaging efficiency are necessarily due to differences in their secondary
      structures and/or three-dimensional (3D) sizes. For example, the heterologous
      RNA1 of brome mosaic virus (BMV) is packaged three times more efficiently by CCMV
      CP than is RNA1 of CCMV, even though the two RNAs have virtually identical
      lengths. Finally, we show that in an assembly mixture at neutral pH, CP binds
      reversibly to the RNA and there is a reversible equilibrium between all the
      various RNA/CP complexes. At acidic pH, excess protein unbinds from RNA/CP
      complexes and nucleocapsids form irreversibly.

PMID- 22951823
TI  - Cyclin-dependent kinase 2 phosphorylates s/t-p sites in the hepadnavirus core
      protein C-terminal domain and is incorporated into viral capsids.
AB  - Phosphorylation of the hepadnavirus core protein C-terminal domain (CTD) is
      important for viral RNA packaging, reverse transcription, and subcellular
      localization. Hepadnavirus capsids also package a cellular kinase. The identity
      of the host kinase that phosphorylates the core CTD or gets packaged remains to
      be resolved. In particular, both the human hepatitis B virus (HBV) and duck
      hepatitis B virus (DHBV) core CTDs harbor several conserved serine/threonine
      proline (S/T-P) sites whose phosphorylation state is known to regulate CTD
      functions. We report here that the endogenous kinase in the HBV capsids was
      blocked by chemical inhibitors of the cyclin-dependent kinases (CDKs), in
      particular, CDK2 inhibitors. The kinase phosphorylated the HBV CTD at the serine
      proline (S-P) sites. Furthermore, we were able to detect CDK2 in purified HBV
      capsids by immunoblotting. Purified CDK2 phosphorylated the S/T-P sites of the
      HBV and DHBV CTD in vitro. Inhibitors of CDKs, of CDK2 in particular, decreased
      both HBV and DHBV CTD phosphorylation in vivo. Moreover, CDK2 inhibitors blocked
      DHBV CTD phosphorylation, specifically at the S/T-P sites, in a mammalian cell
      lysate. These results indicate that cellular CDK2 phosphorylates the functionally
      critical S/T-P sites of the hepadnavirus core CTD and is incorporated into viral
      capsids.

PMID- 22951824
TI  - A mouse model for the study of contact-dependent transmission of influenza A
      virus and the factors that govern transmissibility.
AB  - Influenza A virus transmission by direct contact is not well characterized. Here,
      we describe a mouse model for investigation of factors regulating contact
      dependent transmission. Strains within the H3N2 but not H1N1 subtype of influenza
      virus were transmissible, and reverse-engineered viruses representing hybrids of
      these subtypes showed that the viral hemagglutinin is a determinant of the
      transmissible phenotype. Transmission to contact mice occurred within the first 6
      to 54 h after cohousing with directly infected index mice, and the proportion of
      contacts infected within this period was reduced if the index mice had been
      preinfected with a heterologous subtype virus. A threshold level of virus present
      in the saliva of the index mice was identified, above which the likelihood of
      transmission was greatly increased. There was no correlation with transmission
      and viral loads in the nose or lung. This model could be useful for preclinical
      evaluation of antiviral and vaccine efficacy in combating contact-dependent
      transmission of influenza.

PMID- 22951825
TI  - A neonatal mouse model of coxsackievirus A16 for vaccine evaluation.
AB  - To evaluate vaccine efficacy in protecting against coxsackievirus A16 (CA16),
      which causes human hand, foot, and mouth disease (HFMD), we established the first
      neonatal mouse model. In this article, we report data concerning CA16-induced
      pathological changes, and we demonstrate that anti-CA16 antibody can protect mice
      against lethal challenge and that the neonatal mouse model could be used to
      evaluate vaccine efficacy. To establish a mouse model, a BJCA08/CA16 strain (at
      260 50% lethal doses [LD(50)]) was isolated from a patient and used to
      intracerebrally (i.c.) inoculate neonatal mice. The infection resulted in
      wasting, hind-limb paralysis, and even death. Pathological examination and
      immunohistochemistry (IHC) staining indicated that BJCA08 had a strong tropism to
      muscle and caused severe necrosis in skeletal and cardiac muscles. We then found
      that BJCA08 pretreated with goat anti-G10/CA16 serum could significantly lose its
      lethal effect in neonatal mice. When the anti-G10 serum was intraperitoneally
      (i.p.) injected into the neonatal mice and, within 1 h, the same mice were
      intracerebrally inoculated with BJCA08, there was significant passive
      immunization protection. In a separate experiment, female mice were immunized
      with formaldehyde-inactivated G10/CA16 and BJCA08/CA16 and then allowed to mate 1
      h after the first immunization. We found that there was significant protection
      against BJCA08 for neonatal mice born to the immunized dams. These data
      demonstrated that anti-CA16 antibody may block virus invasion and protect mice
      against lethal challenge, and that the neonatal mouse model was a viable tool for
      evaluating vaccine efficacy.

PMID- 22951826
TI  - Type I interferon induction during influenza virus infection increases
      susceptibility to secondary Streptococcus pneumoniae infection by negative
      regulation of gammadelta T cells.
AB  - The majority of deaths following influenza virus infection result from secondary
      bacterial superinfection, most commonly caused by Streptococcus pneumoniae.
      Several models have been proposed to explain how primary respiratory viral
      infections exacerbate secondary bacterial disease, but the mechanistic
      explanations have been contradictory. In this study, mice were infected with S.
      pneumoniae at different days after primary influenza A (X31) virus infection. Our
      findings show that the induction of type I interferons (IFNs) during a primary
      nonlethal influenza virus infection is sufficient to promote a deadly S.
      pneumoniae secondary infection. Moreover, mice deficient in type I interferon
      receptor (IFNAR knockout [KO] mice) effectively cleared the secondary bacterial
      infection from their lungs, increased the recruitment of neutrophils, and
      demonstrated an enhanced innate expression of interleukin-17 (IL-17) relative to
      wild-type (WT) mice. Lung gammadelta T cells were responsible for almost all IL
      17 production, and their function is compromised during secondary S. pneumoniae
      infection of WT but not IFNAR KO mice. Adoptive transfer of gammadelta T cells
      from IFNAR KO mice reduced the susceptibility to secondary S. pneumoniae
      infection in the lung of WT mice. Altogether, our study highlights the importance
      of type I interferon as a key master regulator that is exploited by opportunistic
      pathogens such as S. pneumoniae. Our findings may be utilized to design effective
      preventive and therapeutic strategies that may be beneficial for coinfected
      patients during influenza epidemics.

PMID- 22951827
TI  - Chromatin assembly on herpes simplex virus 1 DNA early during a lytic infection
      is Asf1a dependent.
AB  - Herpes simplex virus (HSV) is a large DNA virus which is characterized by its
      ability to form latent infections in neurons of the peripheral nervous system.
      Although histones are found in the capsids of small DNA viruses (papovaviruses),
      none are found in the capsids of large HSV. However, after entry into the
      infected cell nucleus, the HSV genome begins to associate with nucleosomes during
      the earliest stages of infection. In contrast, late during infection, newly
      replicated viral DNA does not appear to associate with nucleosomes, suggesting
      that histones are deposited specifically on input viral DNA. The mechanisms of
      deposition and removing histones from the viral genome are unclear. Recently,
      histone chaperones, involved in the assembly and disassembly of nucleosomes, have
      been identified. Human antisilencing factor 1 (Asf1) is one such factor which is
      involved in both the assembly and disassembly of nucleosomes in cellular systems.
      In this study, we have examined the effect of small interfering RNA (siRNA)
      knockdown of Asf1a on HSV infections in HeLa cells. Both viral replication and
      growth were found to be decreased. Also, viral DNA was significantly less
      protected from micrococcal nuclease (MNase) digestion up to 6 h postinfection
      (hpi). However, transcription of the immediate early (IE) genes ICP0 and ICP4 was
      significantly upregulated at 3 h postinfection. Also, these genes were found to
      be less protected from MNase digestion and, therefore, less associated with
      nucleosomes. These results suggest that Asf1a plays a role in regulating IE genes
      by assembling chromatin onto histone-free viral DNA by 3 h postinfection.

PMID- 22951828
TI  - Persistence of Epstein-Barr virus in self-reactive memory B cells.
AB  - Epstein-Barr virus infection has been epidemiologically associated with the
      development of multiple autoimmune diseases, particularly systemic lupus
      erythematosus and multiple sclerosis. Currently, there is no known mechanism that
      can account for these associations. The germinal-center (GC) model of EBV
      infection and persistence proposes that EBV gains access to the memory B cell
      compartment via GC reactions by driving infected cells to differentiate using the
      virus-encoded LMP1 and LMP2a proteins, which act as functional homologues of CD40
      and the B cell receptor, respectively. The ability of LMP2a, when expressed in
      mice, to allow escape of autoreactive B cells suggests that it could perform a
      similar role in infected GC B cells, permitting the survival of potentially
      pathogenic autoreactive B cells. To test this hypothesis, we cloned and expressed
      antibodies from EBV(+) and EBV(-) memory B cells present during acute infection
      and profiled their self- and polyreactivity. We find that EBV does persist within
      self- and polyreactive B cells but find no evidence that it favors the survival
      of pathogenic autoreactive B cells. On the contrary, EBV(+) memory B cells
      express lower levels of self-reactive and especially polyreactive antibodies than
      their uninfected counterparts do. Our work suggests that EBV has only a modest
      effect on the GC process, which allows it to access and persist within a subtly
      unique niche of the memory compartment characterized by relatively low levels of
      self- and polyreactivity. We suggest that this might reflect an active process
      where EBV and its human host have coevolved so as to minimize the virus's
      potential to contribute to autoimmune disease.

PMID- 22951829
TI  - Hepatitis C virus activates Bcl-2 and MMP-2 expression through multiple cellular
      signaling pathways.
AB  - Hepatitis C virus (HCV) infection is associated with numerous liver diseases and
      causes serious global health problems, but the mechanisms underlying the
      pathogenesis of HCV infections remain largely unknown. In this study, we
      demonstrate that signal transducer and activator of transcription 3 (STAT3),
      matrix metalloproteinase-2 (MMP-2), and B-cell lymphoma 2 (Bcl-2) are
      significantly stimulated in HCV-infected patients. We further show that HCV
      activates STAT3, MMP-2, Bcl-2, extracellular regulated protein kinase (ERK), and
      c-Jun N-terminal kinase (JNK) in infected Huh7.5.1 cells. Functional screening of
      HCV proteins revealed that nonstructural protein 4B (NS4B) is responsible for the
      activation of MMP-2 and Bcl-2 by stimulating STAT3 through repression of the
      suppressor of cytokine signaling 3 (SOCS3). Our results also demonstrate that
      multiple signaling cascades, including several members of the protein kinase C
      (PKC) family, JNK, ERK, and STAT3, play critical roles in the activation of MMP-2
      and Bcl-2 mediated by NS4B. Further studies revealed that the C-terminal domain
      (CTD) of NS4B is sufficient for the activation of STAT3, JNK, ERK, MMP-2, and Bcl
      2. We also show that amino acids 227 to 250 of NS4B are essential for regulation
      of STAT3, JNK, ERK, MMP-2, and Bcl-2, and among them, three residues (237L, 239S,
      and 245L) are crucial for this regulation. Thus, we reveal a novel mechanism
      underlying HCV pathogenesis in which multiple intracellular signaling cascades
      are cooperatively involved in the activation of two important cellular factors,
      MMP-2 and Bcl-2, in response to HCV infection.

PMID- 22951830
TI  - Distribution and phosphorylation of the basic protein P6.9 of Autographa
      californica nucleopolyhedrovirus.
AB  - A protamine-like protein named P6.9 is thought to play a role in the condensation
      of genomes of the baculovirus Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) during an infection. Previous studies have shown
      that P6.9 is phosphorylated immediately upon synthesis and dephosphorylated upon
      the entry of the P6.9-DNA complex into the capsid. Here, we investigate the
      dynamic distribution of P6.9 in AcMNPV-infected Spodoptera frugiperda cells using
      an influenza virus hemagglutinin (HA)-tagged P6.9. Although a portion of P6.9-HA
      localized to the virogenic stroma, which is the center of viral DNA replication,
      transcription, and nucleocapsid assembly, the majority of P6.9-HA was distributed
      near the inner nuclear membrane throughout the course of infection. Antiserum
      against P6.9 detected specific phosphorylated forms of P6.9 at the edge of, but
      not within, the electron-dense matte regions of the virogenic stroma. Further
      analysis using immunoblotting revealed that at least 11 different phosphorylated
      forms of P6.9, as well as dephosphorylated P6.9, were present in association with
      occlusion-derived virions, although only dephosphorylated P6.9 was associated
      with budded virions.

PMID- 22951831
TI  - Epstein-Barr virus latent membrane protein 1 regulates the function of interferon
      regulatory factor 7 by inducing its sumoylation.
AB  - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) induces multiple signal
      transduction pathways during latent EBV infection via its C-terminal activating
      region 1 (CTAR1), CTAR2, and the less-studied CTAR3. One mechanism by which LMP1
      regulates cellular activation is through the induction of protein
      posttranslational modifications, including phosphorylation and ubiquitination. We
      recently documented that LMP1 induces a third major protein modification by
      physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and
      inducing the sumoylation of cellular proteins in latently infected cells. We have
      now identified a specific target of LMP1-induced sumoylation, interferon
      regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces
      the sumoylation of IRF7, limiting its transcriptional activity and modulating the
      activation of innate immune responses. Our data show that endogenously sumoylated
      IRF7 is detected in latently infected EBV lymphoblastoid cell lines. LMP1
      expression coincided with increased sumoylation of IRF7 in a CTAR3-dependent
      manner. Additional experiments show that LMP1 CTAR3-induced sumoylation regulates
      the expression and function of IRF7 by decreasing its turnover, increasing its
      nuclear retention, decreasing its DNA binding, and limiting its transcriptional
      activation. Finally, we identified that IRF7 is sumoylated at lysine 452. These
      data demonstrate that LMP1 CTAR3 does in fact function in intracellular
      signaling, leading to biologic effects. We propose that CTAR3 is an important
      signaling region of LMP1 that regulates protein function by sumoylation. We have
      shown specifically that LMP1 CTAR3, in cooperation with CTAR2, can limit the
      ability of IRF7 to induce innate immune responses by inducing the sumoylation of
      IRF7.

PMID- 22951832
TI  - Adaptive immunity restricts replication of novel murine astroviruses.
AB  - The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a
      lack of a small-animal model of disease. Using shotgun sequencing and a custom
      analysis pipeline, we identified two novel astroviruses capable of infecting
      research mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis
      revealed the presence of at least two additional viruses (MuAstV STL3 and STL4),
      suggestive of a diverse population of murine astroviruses in research mice.
      Complete genomic characterization and subsequent phylogenetic analysis showed
      that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely
      members of a new mamastrovirus genogroup. Using Rag1(-/-) mice deficient in B and
      T cells, we demonstrate that adaptive immunity is required to control MuAstV
      infection. Furthermore, using Stat1(-/-) mice deficient in innate signaling, we
      demonstrate a role for the innate immune response in the control of MuAstV
      replication. Our results demonstrate that MuAstV STL permits the study of the
      mechanisms of astrovirus infection and host-pathogen interactions in a
      genetically manipulable small-animal model. Finally, we detected MuAstV in
      commercially available mice, suggesting that these viruses may be present in
      academic and commercial research mouse facilities, with possible implications for
      interpretation of data generated in current mouse models of disease.

PMID- 22951833
TI  - Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from
      homologous and heterologous wild-type H5N1 influenza challenge and controls viral
      loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.
AB  - Recombinant hemagglutinin from influenza viruses with pandemic potential can be
      produced rapidly in various cell substrates. In this study, we compared the
      functionality and immunogenicity of bacterially produced oligomeric or monomeric
      HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed
      subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or
      heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated
      twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur)
      emulsified with Titermax adjuvant and were challenged with wild-type homologous
      (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005;
      clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and
      the SU-H5N1 vaccine provided protection against the lethality and morbidity of
      homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated
      more cross-neutralizing antibodies and higher levels of serum antibody binding to
      HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU
      H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly,
      viral loads after heterologous H5N1 challenge were more efficiently controlled in
      ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated
      ferrets. The reduction of viral loads in the nasal washes correlated strongly
      with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and
      clade 2.2 viruses, as measured by SPR. This is the first study to show the role
      of antibody avidity for the HA1 globular head domain in reduction of viral loads
      in the upper respiratory tract, which could significantly reduce viral
      transmission.

PMID- 22951834
TI  - Upstream AUG codons in the simian immunodeficiency virus SIVmac239 genome
      regulate Rev and Env protein translation.
AB  - The mRNAs encoding the Rev and Env proteins of simian immunodeficiency virus
      (SIV) are unique because upstream translation start codons are present that may
      modulate the expression of these viral proteins. This is true for the regular
      mRNAs, but we also report novel mRNA splicing variants that encode up to five
      upstream AUG (uAUG) codons. Their influence on Rev and Env translation was
      measured by mutational inactivation in reporter constructs and in the SIVmac239
      strain. An intricate regulatory mechanism was disclosed that allows the virus to
      express a balanced amount of these two proteins. This insight also allows the
      design of vector constructs that efficiently express these proteins.

PMID- 22951835
TI  - Conserved fiber-penton base interaction revealed by nearly atomic resolution cryo
      electron microscopy of the structure of adenovirus provides insight into receptor
      interaction.
AB  - Adenovirus (Ad) cell attachment is initiated by the attachment of the fiber
      protein to a primary receptor (usually CAR or CD46). This event is followed by
      the engagement of the penton base protein with a secondary receptor (integrin)
      via its loop region, which contains an Arg-Gly-Asp (RGD) motif, to trigger virus
      internalization. To understand the well-orchestrated adenovirus cell attachment
      process that involves the fiber and the penton base, we reconstructed the
      structure of an Ad5F35 capsid, comprising an adenovirus type 5 (Ad5) capsid
      pseudotyped with an Ad35 fiber, at a resolution of approximately 4.2 A. The fiber
      penton base interaction in the cryo-electron microscopic (cryo-EM) structure of
      Ad5F35 is similar to that in the cryo-EM structure of Ad5, indicating that the
      fiber-penton base interaction of adenovirus is conserved. Our structure also
      confirms that the C-terminal segment of the fiber tail domain constitutes the
      bottom trunk of the fiber shaft. Based on the conserved fiber-penton base
      interaction, we have proposed a model for the interaction of Ad5F35 with its
      primary and secondary receptors. This model could provide insight for designing
      adenovirus gene delivery vectors.

PMID- 22951836
TI  - Evolutionary conservation of the PA-X open reading frame in segment 3 of
      influenza A virus.
AB  - PA-X is a fusion protein of influenza A virus encoded in part from a +1
      frameshifted X open reading frame (X-ORF) in segment 3. We show that the X-ORFs
      of diverse influenza A viruses can be divided into two groups that differ in
      selection pressure and likely function, reflected in the presence of an internal
      stop codon and a change in synonymous diversity. Notably, truncated forms of PA-X
      evolved convergently in swine and dogs, suggesting a strong species-specific
      effect.

PMID- 22951837
TI  - Structure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical
      homo-oligomers and the role of caspase-3 cleavage.
AB  - Crimean-Congo hemorrhagic fever, a severe hemorrhagic disease found throughout
      Africa, Europe, and Asia, is caused by the tick-borne Crimean-Congo hemorrhagic
      fever virus (CCHFV). CCHFV is a negative-sense single-stranded RNA (ssRNA) virus
      belonging to the Nairovirus genus of the Bunyaviridae family. Its genome of three
      single-stranded RNA segments is encapsidated by the nucleocapsid protein (CCHFV
      N) to form the ribonucleoprotein complex. This ribonucleoprotein complex is
      required during replication and transcription of the viral genomic RNA. Here, we
      present the crystal structures of the CCHFV N in two distinct forms, an
      oligomeric form comprised of double antiparallel superhelices and a monomeric
      form. The head-to-tail interaction of the stalk region of one CCHFV N subunit
      with the base of the globular body of the adjacent subunit stabilizes the helical
      organization of the oligomeric form of CCHFV N. It also masks the conserved
      caspase-3 cleavage site present at the tip of the stalk region from host cell
      caspase-3 interaction and cleavage. By incubation with primer-length ssRNAs, we
      also obtained the crystal structure of CCHFV N in its monomeric form, which is
      similar to a recently published structure. The conformational change of CCHFV N
      upon deoligomerization results in the exposure of the caspase-3 cleavage site and
      subjects CCHFV N to caspase-3 cleavage. Mutations of this cleavage site inhibit
      cleavage by caspase-3 and result in enhanced viral polymerase activity. Thus,
      cleavage of CCHFV N by host cell caspase-3 appears to be crucial for controlling
      viral RNA synthesis and represents an important host defense mechanism against
      CCHFV infection.

PMID- 22951838
TI  - Deletion of the herpes simplex virus 1 UL49 gene results in mRNA and protein
      translation defects that are complemented by secondary mutations in UL41.
AB  - Herpes simplex virus 1 (HSV-1) virions, like those of all herpesviruses, contain
      a protein layer termed the tegument localized between the capsid and the
      envelope. VP22, encoded by the U(L)49 gene, is one of the most abundant tegument
      proteins in HSV-1 virions. Studies with a U(L)49-null mutant showed that the
      absence of VP22 resulted in decreased protein synthesis at late times in
      infection. VP22 is known to form a tripartite complex with VP16 and vhs through
      direct interactions with VP16. Given that U(L)49-null mutants have been shown to
      acquire spontaneous secondary mutations in the U(L)41 gene, which encodes vhs, we
      hypothesized that VP22 and vhs may play antagonistic roles during HSV-1
      infections. In the present study, we show that the protein synthesis defect
      observed in U(L)49-null virus infections was rescued by a secondary, compensatory
      frameshift mutation in U(L)41. A double mutant bearing a deletion of U(L)49 and a
      point mutation in vhs previously shown to specifically abrogate vhs's RNase
      activity also resulted in a rescue of protein synthesis. To determine whether the
      U(L)49(-) protein synthesis defect, and the rescue by secondary mutations in vhs,
      occurred at the mRNA and/or translational levels, quantitative reverse
      transcriptase PCR (qRT-PCR) and polysome analyses were performed. We found that
      the absence of VP22 caused a small decrease in mRNA levels as well as a defect in
      polysome assembly that was independent of mRNA abundance. Both defects were
      complemented by the secondary mutations in vhs, indicating functional interplay
      between VP22 and vhs in both accumulation and translation of viral mRNAs.

PMID- 22951839
TI  - The Asian-American E6 variant protein of human papillomavirus 16 alone is
      sufficient to promote immortalization, transformation, and migration of primary
      human foreskin keratinocytes.
AB  - We examined how well the human papillomavirus (HPV) E6 oncogene can function in
      the absence of the E7 oncogene during the carcinogenic process in human
      keratinocytes using a common HPV variant strongly associated with cervical
      cancer: the Asian-American E6 variant (AAE6). This E6 variant is 20 times more
      frequently detected in cervical cancer than the prototype European E6 variant, as
      evidenced by independent epidemiological data. Using cell culture and cell-based
      functional assays, we assessed how this variant can perform crucial
      carcinogenesis steps compared to the prototype E6 variant. The ability to
      immortalize and transform primary human foreskin keratinocytes (PHFKs) to acquire
      resilient phenotypes and the ability to promote cell migration were evaluated.
      The immortalization capability was assayed based on population doublings, number
      of passages, surpassing mortality stages 1 and 2, human telomerase reverse
      transcriptase (hTERT) expression, and the ability to overcome G(1) arrest via p53
      degradation. Transformation and migration efficiency were analyzed using a
      combination of functional cell-based assays. We observed that either AAE6 or
      prototype E6 proteins alone were sufficient to immortalize PHFKs, although AAE6
      was more potent in doing so. The AAE6 variant protein alone pushed PHFKs through
      transformation and significantly increased their migration ability over that of
      the E6 prototype. Our findings are in line with epidemiological data that the AA
      variant of HPV16 confers an increased risk over the European prototype for
      cervical cancer, as evidenced by a superior immortalization, transformation, and
      metastatic potential.

PMID- 22951840
TI  - Mutations in the M-gene segment can substantially increase replication efficiency
      of NS1 deletion influenza A virus in MDCK cells.
AB  - Influenza viruses unable to express NS1 protein (delNS1) replicate poorly and
      induce large amounts of interferon (IFN). They are therefore considered candidate
      viruses for live-attenuated influenza vaccines. Their attenuated replication is
      generally assumed to result from the inability to counter the antiviral host
      response, as delNS1 viruses replicate efficiently in Vero cells, which lack IFN
      expression. In this study, delNS1 virus was parallel passaged on IFN-competent
      MDCK cells, which resulted in two strains that were able to replicate to high
      virus titers in MDCK cells due to adaptive mutations especially in the M-gene
      segment but also in the NP and NS gene segments. Most notable were clustered U-to
      C mutations in the M segment of both strains and clustered A-to-G mutations in
      the NS segment of one strain, which presumably resulted from host cell-mediated
      RNA editing. The M segment mutations in both strains changed the ratio of M1 to
      M2 expression, probably by affecting splicing efficiency. In one virus, 2 amino
      acid substitutions in M1 additionally enhanced virus replication, possibly
      through changes in the M1 distribution between the nucleus and the cytoplasm.
      Both adapted viruses induced levels of IFN equal to that of the original delNS1
      virus. These results show that the increased replication of the adapted viruses
      is not primarily due to altered IFN induction but rather is related to changes in
      M1 expression or localization. The mutations identified in this paper may be used
      to enhance delNS1 virus replication for vaccine production.

PMID- 22951841
TI  - Reversible inhibition of fusion activity of a paramyxovirus fusion protein by an
      engineered disulfide bond in the membrane-proximal external region.
AB  - Cysteines were introduced into the membrane-proximal external region (MPER) of
      the paramyxovirus F protein. A disulfide bond formed, and the mutant protein was
      expressed at the cell surface but was fusion inactive. Reduction of the disulfide
      bond restored fusion activity. The data indicate that in addition to dissociation
      of the three-helix bundle stalk domain of prefusion F, the MPER region also needs
      to separate for F to be able to refold and cause fusion.

PMID- 22951842
TI  - Probing the early temporal and spatial interaction of the Sindbis virus capsid
      and E2 proteins with reverse genetics.
AB  - A 7-A cryoelectron microscopy-based reconstruction of Sindbis virus (SINV) was
      recently generated. Fitting the crystal structure of the SINV capsid protein (Cp)
      into the density map revealed that the F2-G2 loop of the Cp was shifted away from
      cytoplasmic domain of E2 (cdE2) in the 7-A reconstruction relative to its
      position in the Cp crystal structure. Furthermore, the reconstruction
      demonstrated that residue E395 in region I of the cytoplasmic domain of the E2
      envelope protein (cdE2-RI) and K252 of Cp, part of the Cp F2-G2 loop, formed a
      putative salt bridge in the virion. We generated amino acid substitutions at
      residues K250 and K252 of the SINV Cp and explored the resulting phenotypes. In
      the context of cells infected with wild-type or mutant virus, reversing the
      charge of these two residues resulted in the appearance of Cp aggregates around
      cytopathic vacuole type I (CPV-I) structures, the absence of nucleocapsid (NC)
      formation, and a lack of virus particle release in the infected mammalian cell.
      However, expressing the same Cp mutants in the cell without the envelope proteins
      or expressing and purifying the mutants from an Escherichia coli expression
      system and assembling in vitro yielded NC assembly in all cases. In addition,
      second-site mutations within cdE2 restored NC assembly but not release of
      infectious particles. Our data suggest an early temporal and spatial interaction
      between cdE2-RI and the Cp F2-G2 loop that, when ablated, leads to the absence of
      NC assembly. This interaction also appears to be important for budding of virus
      particles.

PMID- 22951844
TI  - [A perspective to lipid lowering therapy after ESC/EAS guidelines for the
      management of dyslipidaemias and the European guidelines on cardiovascular
      disease prevention in clinical practice].

PMID- 22951843
TI  - Relationship between within-host fitness and virulence in the vesicular
      stomatitis virus: correlation with partial decoupling.
AB  - Given the parasitic nature of viruses, it is sometimes assumed that rates of
      viral replication and dissemination within hosts (within-host fitness) correlate
      with virulence. However, there is currently little empirical evidence supporting
      this principle. To test this, we quantified the fitness and virulence of 21
      single- or double-nucleotide mutants of the vesicular stomatitis virus in baby
      hamster kidney cells (BHK-21). We found that, overall, these two traits
      correlated positively, but significant outliers were identified. Particularly, a
      single mutation in the conserved C terminus of the N nucleocapsid (U1323A) had a
      strongly deleterious fitness effect but did not alter or even slightly increased
      virulence. We also found a double mutant of the M matrix protein and G
      glycoprotein (U2617G/A3802G mutant) with high fitness yet low virulence. We
      further characterized these mutants in primary cultures from mouse brain cells
      and in vivo and found that their relative fitness values were similar to those
      observed in BHK-21 cells. The mutations had weak effects on the virus-induced
      death rate of total brain cells, although they specifically reduced neuron death
      rates. Furthermore, increased apoptosis levels were detected in neurons infected
      with the U2617G/A3802G mutant, consistent with its known inability to block
      interferon secretion. In vivo, this mutant had reduced virulence and, despite its
      low brain titer, it retained a relatively high fitness value owing to its ability
      to suppress competitor viruses. Overall, our results are in broad agreement with
      the notion that viral fitness and virulence should be positively correlated but
      show that certain mutations can break this association and that the fitness
      virulence relationship can depend on complex virus-host and virus-virus
      interactions.

PMID- 22951845
TI  - [Heart failure prevalence and predictors in Turkey: HAPPY study].
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of heart
      failure (HF) in adult residents of Turkey based on echocardiography and N
      terminal B type natriuretic factor. STUDY DESIGN: 4650 randomly selected
      residents aged >= 35 years were enrolled. Height, weight, waist and hip
      circumference, and blood pressure measurements were taken, and a 12-lead ECG was
      performed. Advanced age, hypertension (HT), diabetes mellitus (DM), obesity, and
      chronic renal failure (CRF) were assessed. History of any heart disease, any
      abnormal ECG, or an NT-proBNP >= 120 pg/mL was accepted as echocardiography
      indication. Patients with systolic and/or diastolic dysfunction, or NT-proBNP >=
      2000 pg/mL were classified as having HF if their functional capacity was NYHA >=
      Class II, and were classified as having asymptomatic left ventricular dysfunction
      (ASVD) if their functional capacity was NYHA <Class I. RESULTS: The absolute and
      estimated prevalences were 2.9% and 6.9% for HF, and 4.8% and 7.9% for ASVD,
      respectively. Advanced age, male gender, history of heart disease, HT and CRF
      were independent predictors of HF. In patients with ejection fraction (EF) <50%,
      HF prevalence was higher in men, while HF prevalences were higher in women when
      EF >= 50%. In global sum, HF and ALVD prevalence were similar in male and
      females. CONCLUSION: The prevalences of HF and ASVD are higher in Turkey when
      compared with western countries, despite a younger Turkish population. The
      established predictors of HF are valid for Turkey as well. There is a significant
      ASVD population in Turkey with similar characteristics and risk factors to HF.
      Focusing on the early detection and treatment of ASVD may prevent the progression
      to HF, and therefore would decrease the prevalence of HF in Turkey.

PMID- 22951846
TI  - Elevated carbohydrate antigen 125 levels in patients with aortic stenosis:
      relation to clinical severity and echocardiographic parameters.
AB  - OBJECTIVES: Carbohydrate antigen 125 (CA 125), known as a tumor marker for
      ovarian cancer, has been reported to increase in relation to disease severity in
      heart failure patients with systolic dysfunction. Aortic stenosis (AS) has a wide
      clinical spectrum that often includes heart failure symptoms. The purpose of the
      present study is to evaluate the serum levels of CA 125 in patients with AS and
      its relation to clinical severity and echocardiographic parameters. STUDY DESIGN:
      The study group consisted of 42 patients (20 males, 22 females, mean age 62.5 +/-
      14.9 years) with AS and 35 healthy controls (17 men, 18 women; mean age 59.0 +/-
      9.1 years). All patients and control subjects underwent chest X-ray and
      echocardiographic evaluation. We measured serum CA 125 values in patients with AS
      and control subjects. RESULTS: The median (interquartile range) CA 125 level was
      significantly higher among AS patients than in the control group in covariate
      analysis (9.4 [2.5-38.1] vs. 6.8 [4.4-13.9] U/ml respectively; p=0.001). Spearman
      correlation analysis in the whole group indicated that CA 125 was positively
      correlated with aortic mean gradient (p=0.007, r=0.30) and creatinine levels
      (p=0.02, r=0.26). CONCLUSION: We found that CA 125 levels were elevated in
      patients with AS and were correlated with mean gradient and creatinine levels.

PMID- 22951847
TI  - The relationship between serum total testosterone and 24-hour urinary sodium
      excretion in never-treated stage 1 essential hypertensive patients.
AB  - OBJECTIVES: To study the relationship between serum total testosterone (TT) and
      24-hour urinary sodium excretion in newly diagnosed stage 1 essential
      hypertensive patients with normal renal function. STUDY DESIGN: In total, 80
      never-treated stage 1 hypertensive patients were included. All patients provided
      medical history and underwent physical examination, blood pressure measurement,
      12-lead electrocardiography, routine urine analysis, biochemical analysis, 24
      hour urine collection to measure urinary sodium and protein excretion, and
      creatinine clearance calculation. RESULTS: Pearson correlation analysis revealed
      that logarithmically converted 24-hour urinary sodium excretion was correlated
      with age (r=-0.399, p<0.0001), body mass index, (r=0.304, p=0.006), systolic
      blood pressure (r=0.394, p<0.0001), serum potassium (r=0.233, p=0.037),
      creatinine clearance (r=0.600, p<0.0001), and logarithmically converted serum TT
      (r=-0.272, p=0.015). Stepwise linear regression analysis revealed that age
      (p<0.0001), creatinine clearance (p=0.015), systolic blood pressure (p<0.0001),
      potassium (p=0.021), and serum TT (p=0.002) were independently related to
      logarithmically converted 24-hour sodium excretion. CONCLUSION: We demonstrated
      that serum TT levels were independently related to 24-hour urinary sodium amount.

PMID- 22951848
TI  - Comparison of long term clinical outcomes, event free survival rates of patients
      undergoing enhanced external counterpulsation for coronary artery disease in the
      United States and Turkey.
AB  - OBJECTIVES: This study assessed the long-term efficacy of EECP (Enhanced External
      Counterpulsation) in Turkish (TR) patients initially and compared these results
      with the United States (US) in a real world setting. STUDY DESIGN: In this study,
      2072 patients were treated and followed in the US and 82 patients were treated
      and followed in TR. The International EECP Patient Registry Phase I and II was
      initiated and coordinated at the University of Pittsburgh. The aim of the
      "registry" was to assess the outcomes of clinical trials in a real world setting.
      Another unique feature of this study was to enroll patients not only from
      university hospitals but also from private hospitals, educational hospitals, and
      treatment centers. RESULTS: TR patients had less diabetes, hypertension, and
      hyperlipidemia than US patients (p<0.01). TR patients also had a higher
      proportion of diastolic augmentation (p<0.001). Both groups showed a significant
      reduction in the severity of angina after a 35 h EECP course (p<0.001). Major
      Adverse Cardiac Events (MACE) rate (death, coronary artery bypass graft,
      percutaneous coronary intervention, myocardial infarction) was low in both groups
      during treatment (2.5% vs. 2.7%). At 1 year follow up, 84% of TR and 76% of US
      patients had maintained the improvement of angina. CONCLUSION: Patients
      presenting for EECP treatment from TR had different baseline profiles from US
      patients. However, despite the high risk baseline characteristics, both cohorts
      achieved similar reduction in angina. In the long term follow-up, the MACE rate
      was low and the improvement after EECP was sustained in most of the patients.

PMID- 22951849
TI  - Comparison of DDD versus VVIR pacing modes in elderly patients with
      atrioventricular block.
AB  - OBJECTIVES: Dual-chamber pacing is believed to have an advantage over single
      chamber ventricular pacing. The aim of this study was to determine whether
      elderly patients who have implanted pacemakers for complete atrioventricular
      block gain significant benefits from dual-chamber (DDD) pacemakers compared with
      single chamber ventricular (VVIR) pacemakers. STUDY DESIGN: This study was
      designed as a randomized, two-period crossover study-each pacing mode was
      maintained for 1 month. Thirty patients (16 men, mean age 68.87 +/- 6.89 years)
      with implanted DDD pacemakers were submitted to a standard protocol, which
      included an interview, pacemaker syndrome assessment, health related quality of
      life (HRQoL) questionnaires assessed by an SF-36 test, 6-minute walk test (6MWT),
      and transthoracic echocardiographic examinations. All of these parameters were
      obtained on both DDD and VVIR mode pacing. Paired data were compared. RESULTS:
      HRQoL scores were similar, and 6MWT results did not differ between the two
      groups. VVIR pacing elicited significant enlargement of the left atrium and
      impaired left ventricular diastolic functions as compared with DDD pacing. Two
      patients reported subclinical pacemaker syndrome, but this was not statistically
      significant. CONCLUSION: Our study revealed that in active elderly patients with
      complete heart block, DDD pacing and VVIR pacing yielded similar improvements in
      QoL and exercise performance. However, after a short follow-up period, we noted
      that VVIR pacing caused significant left atrial enlargement and impaired left
      ventricular diastolic functions.

PMID- 22951850
TI  - [Echocardiographic evaluation of left ventricular function in normotansive obese
      children: a comparative analysis according to body mass index].
AB  - OBJECTIVES: The purpose of our study was to determine structural and functional
      changes on left ventricular function (LV) according to body mass index (BMI) in
      normotansive overweight and obese children. STUDY DESIGN: Thirty normotansive
      overweight children (group 2; mean age: 13.2 +/- 2.1 years, BMI: 25-30 kg/m2), 30
      obese children (group 3; mean age: 13.3 +/- 2.0 years, BMI >= 30 kg/m2), and 50
      healthy controls (mean age: 13.2 +/- 1.8 years, BMI: 18-24.9 kg/m2) were included
      in this study. Continuous ambulatory pressure was monitored in the obese group,
      while standard and pulsed wave (PW) Doppler echocardiographic examinations were
      evaluated in all three study groups. RESULTS: In overweight and obese children,
      left atrial volume, left atrial/aortic root diameter ratio, LV interventricular
      septum, LV posterior wall thickness, LV end-diastolic diameter and volume, and LV
      mass were significantly higher than those children in the control group (p<0.01).
      Blood pressure was within the normal range but was increased in the obese groups.
      Transmitral E/A and pulmonary vein (PV) systolic/diastolic velocity (S/D) ratios
      were decreased, but E-wave deceleration time, PVA velocities, and the end
      diastolic distance from the mitral annulus to the LV apex were increased in both
      obese groups (p<0.05). BMI was significantly correlated with duration of obesity
      and LV mass (r=0.527, r=0.506, p<0.01, respectively). Significantly negative
      correlations were found between BMI, Mitral E/A, and PV S/D ratio (r=-0.230, r=
      0.577, p<0.01, respectively). CONCLUSION: Subclinical LV myocardial dysfunction
      was noted in obese subgroups. Determination of diastolic dysfunction by PV PW
      Doppler can be useful a pre-obese period.

PMID- 22951851
TI  - Fenestrated cor triatriatum sinistrum: a case report.
AB  - We present a 20-year-old male patient with cor triatriatum sinistrum with
      fenestrations and long-standing dyspnea on exertion, fatigue, and palpitation. An
      apical early to mid-systolic murmur of grade I-II/VI was heard on cardiac
      auscultation. Electrocardiography showed sinus rhythm and an incomplete right
      bundle branch block. Transthoracic echocardiography showed a membrane dividing
      the left atrium into two compartments. Transesophageal echocardiography showed a
      membrane with fenestrations originating from the left upper pulmonary vein,
      extending to the interatrial septum, and dividing the left atrium into two
      compartments as proximal and distal. Cardiac MR imaging for further detailed
      anatomical assessment demonstrated similar findings without additional anomaly.
      Medical follow-up was conducted due to no pressure gradient across the membrane.

PMID- 22951852
TI  - Adult patient with Shone's syndrome and patent ductus arteriosus: a case report.
AB  - Shone's syndrome is a very rare cardiac malformation composed of four obstructive
      congenital lesions, which include the parachute mitral valve (PMV), supravalvular
      ring, subaortic stenosis, and coarctation of aorta. Diagnosis requires a
      comprehensive examination including a carefully performed echocardiography. It is
      extremely unusual for a patient to remain undiagnosed during adulthood. Here we
      report a 26-year-old male patient with Shone's syndrome and patent ductus
      arteriosus (PDA). The patient reported that he had been suffering from exercise
      intolerance and aggravating dyspnea. Two years ago, he was operated on in another
      hospital based on the wrong diagnosis of mitral valve prolapse and subaortic
      membrane. Transthoracic echocardiography revealed the existence of a PMV, which
      led to severe mitral stenosis through a previously implanted mitral annular ring.
      Other components of Shone's syndrome, subaortic membrane and aortic coarctation,
      together with PDA, were also observed. Another operation was suggested, but the
      patient refused. During the two year follow-up period, in spite of an atrial
      fibrillation attack and deteriorating dyspnea, the patient still did not want
      another operation. Once any of the four components of the Shone's complex is
      detected, clinicians must look for the presence of other lesions.

PMID- 22951853
TI  - Paget-von Schrotter syndrome: upper extremity deep vein thrombosis after heavy
      exercise.
AB  - We present a 52-year-old man with swelling, tightness, heaviness, and redness in
      the right half of his neck, face, upper arm, and right precordial area after
      repetitive exercises. No etiological factors such as trauma, venous catheter,
      malignancy, hematologic disorder history, or any chronic disease were noted. A
      Doppler ultrasound of the upper extremities was performed, which showed a
      complete thrombotic occlusion in the right internal jugular vein, partial
      occlusion in the right brachiocephalic and subclavian veins with thrombosis, and
      chronic thrombosis occluding the left brachial vein. Complete blood cell count,
      coagulation profiles, and rheumatologic and tumor markers were normal. The
      patient reported that he had taken spinning classes for the last 18 months, and
      for the past 4 days he reported that he had done his spinning exercises harder
      and more frequently. The swelling and redness regressed partially on the 3rd day
      of therapy with enoxaparin sodium. In the first month follow-up visit we
      performed a control Doppler ultrasound and it showed partially thrombosed areas
      in the right brachiocephalic and internal jugular veins. Also, chronic thrombosis
      persisted in the left brachial and basilic veins. Computed tomography images
      showed no evidence for malignancy and some sections showed filling defects in the
      vena cava superior, which was attributed to thrombotic materials. The patient was
      successfully treated with anticoagulants for 6 months.

PMID- 22951854
TI  - Lamotrigine related myocarditis: case report.
AB  - Myocarditis can develop secondary to several medications. Here, we report a case
      of myocarditis related to the use of lamotrigine. A 15-year-old boy was admitted
      to another hospital because of a chest pain that was sustained for 30 minutes. He
      was transferred to our hospital after detection of cardiac enzyme elevation. He
      was evaluated in our center, where electrocardiography revealed non-specific ST
      elevation at inferior derivations, and the level of troponin T was found to be
      0.47 ng/ml (0-0.1), while creatinin kinase MB was found to be 38 ng/ml (0-4.97).
      Systolic cardiac functions were normal via echocardiography. Cardiac magnetic
      resonance imaging showed minimal pericardial effusion and a minimal decrease in
      left ventricular function. He was hospitalized with the diagnosis of myocarditis.
      Viral and bacterial agents that can cause myocarditis were excluded via
      serological tests. He had been on a lamotrigine treatment due to epilepsy, and
      after cessation of lamotrigine, his cardiac enzyme levels returned to normal.
      Therefore, we diagnosed him with drug related myocarditis due to lamotrigine. If
      an etiology cannot be found during the evaluation of a myocarditis case, drug
      hypersensitivity should be considered. Changing the responsible drug for
      hypersensitivity may be beneficial for these patients.

PMID- 22951855
TI  - [A case of symptomatic right atrial lipoma].
AB  - Cardiac lipomas are rarely diagnosed tumors of heart. They are encapsulated and
      matured lipoid tumors that are diagnosed equally in all age groups and sexes.
      Cardiac lipoma are diagnosed mostly in the left ventricle, right atrium, and
      interatrial septum. We present a 62-year-old symptomatic patient with right
      atrial lipoma suffering from effort dyspnea, upper extremity and facial edema and
      palpitation, and who had a by-pass operation approximately 1.5 years ago. In
      patient transthorasic echocardiography (TTE) revealed that the right atrial mass.
      It was decided that the audience may be receiving. She underwent interatrial
      septum resection followed by reconstruction of interatrial septum and  atriocaval
      junction. In the third month after the operation, there was no intracardiac mass
      on TTE and right atrial size was within normal limits.

PMID- 22951856
TI  - [A case with tricuspid valve brucella endocarditis presenting with acute right
      heart failure].
AB  - Although the presence of brucella endocarditis is encountered rarely, it is the
      most fetal complication of brucellosis, which is shown to affect the aortic valve
      primarily and the mitral valve secondarily. Involvement of the tricuspid valve is
      extremely rare. A 62-year-old female was admitted with complaints of fever,
      fatigue, difficulty in breathing, and swellings in her legs. A transthoracic
      echocardiogram was performed since acute right heart failure was considered due
      to her symptoms. The echocardiogram showed enlarged right heart chambers, serious
      tricuspid valve insufficiency, and a mass on the tricuspid valve compatible with
      a vegetation moving in and out of the right ventricle. Although no growths were
      observed in the blood culture, antibody titration for brucellosis was found to be
      1/640 (+) in the serological examination. The patient was diagnosed with brucella
      endocarditis and placed on doxycycline, rifampicin, and ceftriaxone treatment for
      eight weeks. At the end of the eight-week treatment, the symptoms of right heart
      failure receded and the patient recovered from the endocarditis. Tricuspid valve
      brucella endocarditis should be considered in patients suffering from acute right
      heart failure accompanied by systemic infection findings since brucellosis is
      presently endemic in Turkey.

PMID- 22951857
TI  - Dysfunction of high-density lipoprotein and its apolipoproteins: new mechanisms
      underlying cardiometabolic risk in the population at large.
AB  - We review the metabolic and residual cardiovascular risk existing in populations
      with prevailing metabolic syndrome (MetS) or in people prone to impaired glucose
      tolerance. Evidence is presented that enhanced systemic inflammation, or
      oxidative stress associated with elevated plasma triglyceride-rich lipoproteins
      and their remnants, and excess oxidized lipoprotein(a) phospholipids underlie
      this risk. The adverse risk profile is augmented by loss of the anti
      inflammatory, anti-oxidative and atheroprotective properties of high-density
      lipoprotein and its apolipoproteins (apo). Common clinical manifestations are
      atherogenic dyslipidemia and hypertriglyceridemia with elevated apoB or
      hypertriglyceridemic waist phenotype. These manifestations are often accompanied
      by such inflammatory mediators/markers as elevated serum apoE, C-reactive
      protein, complement C3, and uric acid levels. Compared with men, peri- and
      postmenopausal women are more commonly and more strongly affected by multiple
      inflammation mediators. The long-term effects of cigarette smoking are not
      adverse in such women, but instead, serve as protection against obesity and other
      health issues. ApoA-I may become dysfunctional in either gender, even in the
      absence of MetS and diabetes. The public health implications of this
      cardiometabolic risk are huge. Much research is needed on this topic to further
      clarify the impact of apoA-I dysfunction, to elucidate the underlying genetics
      and mechanisms, and to determine preventive measures and optimal management.
      Avoiding (abdominal) obesity via lifestyle modifications, including dietary
      changes, improving physical inactivity, and limiting smoking and alcohol
      consumption, are mainstay measures in the prevention and management of pro
      inflammatory states and HDL dysfunction. Omega-3 fatty acids are a good adjunct
      to lower plasma triglycerides. When further treatment is needed, extended-release
      niacin or fibrates, with or without statins, are the best options.

PMID- 22951858
TI  - [How to do vasoreactivity test?].

PMID- 22951859
TI  - Case images: evaluation of early dysfunction of a prosthetic mitral valve by real
      time 3D transesophageal echocardiography.

PMID- 22951860
TI  - [Case images: closure of the coronary to pulmonary artery fistula after
      microcatheter mediated dissection].

PMID- 22951861
TI  - Case images: atrial fibrillation due to right atrial compression in a patient
      with pectus excavatum.

PMID- 22951862
TI  - Case images: percutaneous retrieval of an embolized occluder device from the
      aorta using a goose-neck snare.

PMID- 22951863
TI  - Case images: transcatheter treatment of subclavian and pulmonary steal phenomenon
      in an infant.

PMID- 22951864
TI  - Microencapsulation of self-microemulsifying systems: optimization of shell
      formation phase and hardening process.
AB  - The preparation of microcapsules with a self-microemulsifying system (SMES) core
      using a vibrating nozzle technology was improved with regard to process
      reproducibility and core phase retention. The microcapsule shell was optimized
      for composition of the alginate-pectin (A/P) ratio and hydrophilic filling agent
      content. The best-shaped microcapsules with highest encapsulation efficiency for
      furosemide-loaded SMES were obtained from the shell-formation phase with an A/P
      ratio of 25:75, containing 10% lactose, which was hardened through a one-step
      process. Fluid-bed dried microcapsules were examined for their release
      characteristics and swelling behavior of the polymeric matrix. Incorporation of
      hydrophilic filling agents in the shell-formation phase was shown to be
      successful in limiting the leakage of the core phase during the microcapsule
      production and drying processes. Moreover, the addition of different fillers also
      allows the drug release profile from Ca-alginate/pectinate microcapsules with a
      self-microemulsifying core to be modified.

PMID- 22951865
TI  - Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true
      supersaturation vs. apparent solubility enhancement.
AB  - Amorphous solid dispersions (ASDs) represent a promising formulation approach for
      poorly soluble drugs. We explored the formulation-related impact of ASDs on
      permeation rate, apparent solubility and molecular solubility of the poorly
      soluble drug ABT-102. The influence of fasted state simulated intestinal fluid
      (FaSSIF) as dispersion medium was also studied. ASDs were prepared by hot-melt
      extrusion. Permeation rate was assessed by the Caco-2 transwell assay. Cell
      viability and barrier integrity were assured by AlamarBlue(c), TEER and
      permeability of the hydrophilic marker carboxyfluorescein. Apparent solubility
      and molecular solubility were evaluated by using centrifugation and inverse
      dialysis, respectively. The in vitro permeation rate of ABT-102 from aqueous
      dispersions of the ASD was found 4 times faster than that from the dispersions of
      the crystals, while apparent solubility and molecular solubility of ABT-102 were
      increased. Yet, a further increase in apparent solubility due to micellar
      solubilization as observed when dispersing the ASD in FaSSIF, did not affect
      molecular solubility or permeation rate. Overall, a good correlation between
      permeation rate and molecular solubility but not apparent solubility was seen.

PMID- 22951866
TI  - Cyclosporin nanosphere formulation for ophthalmic administration.
AB  - Cyclosporin A (CsA) is a widely used anti-inflammatory agent for the management
      of dry eye disease, and is available commercially as ophthalmic emulsion
      formulation (RESTASIS((r))). For increasing efficacy, and for reducing local
      toxicity including irritation to eyes, CsA nanosphere (CsA-NS) formulation was
      prepared and evaluated, in this work. CsA-NS formulation was prepared in a pre
      concentrate form, which is a homogeneous solution of a CsA in a mixture of
      surfactants, lipids and solvents and provides nanosphere dispersion when added to
      aqueous medium. CsA-NS formulation was characterized and adjusted for particle
      size, pH, and osmolarity, suitable for ophthalmic administration. Thereafter, CsA
      NS formulation was evaluated for parameters like irritation to eyes and
      penetrability of CsA in the rabbit eyes. Results obtained demonstrated that
      proposed CsA-NS formulation causes less irritation in rabbit eyes, with nearly
      same CsA penetration in the rabbit eyes in comparison to marketed emulsion
      formulation.

PMID- 22951868
TI  - Assessment of the quality of evidence underlying international guidelines in
      liver disease.
AB  - OBJECTIVE: We aimed to describe the overall quality of evidence supporting
      international guidelines in liver disease. METHODS: The quality of evidence
      supporting guidelines from three international liver disease associations was
      graded as high, moderate, or low according to the systems initially used to
      assess the primary literature. RESULTS: Twenty-three current guidelines were
      developed with the use of five evidence-grading systems. Evidence was assessed as
      low-quality (from consensus opinions) in 43.9% of all recommendations.
      Recommendations based on high-quality evidence (from consistent data from
      randomized controlled trials) appeared least frequently. Where guidelines had
      been updated, there was a 22% increase in the total number of recommendations,
      due largely to an increase in recommendations based on low-quality evidence.
      Recommendations revised to include high-quality evidence accounted for only 16.3%
      of all new or updated recommendations. CONCLUSIONS: Guidelines in liver disease
      are heterogeneous. Evidence-based recommendations in these guidelines are most
      frequently based on low-quality evidence.

PMID- 22951869
TI  - Understanding gastroenterologist adherence to polyp surveillance guidelines.

PMID- 22951870
TI  - Physician-patient and patient-family communication after colonoscopy.
AB  - OBJECTIVES: A personal or family history of colorectal adenomas increases the
      risk of colorectal cancer (CRC). We aimed to compare physicians' communication
      with polyp patients vs. non-polyp patients, assess whether polyps or CRC family
      history were associated with physician-patient communication, and describe
      patients' disclosure of colonoscopy and polyp diagnosis to their relatives.
      METHODS: Four hundred nine patients completed an online survey regarding
      physician-patient communication of colonoscopy results, perceived personal and
      familial risk of polyps and CRC, and disclosure of colonoscopy results to
      relatives. RESULTS: Six percent of participants reported that their physicians
      discussed familial risks. Polyp diagnosis and family history predicted physician
      patient discussions about familial CRC risks. Polyp diagnosis predicted physician
      patient discussions of future surveillance. Twenty-two percent of patients told
      none of their relatives that they had a colonoscopy. Family history, gender, and
      education were associated with patient-family communication. CONCLUSIONS: There
      is room for improvement in physician-patient and patient-family communication
      following colonoscopy.

PMID- 22951871
TI  - Images of the month. Painful abdominal distension during pregnancy.

PMID- 22951876
TI  - Genetics of Barrett's: the bigger, the better.
AB  - Barrett's esophagus (BE) is a common lesion that predisposes to a highly fatal
      esophageal adenocarcinoma (EA). There is evidence that BE or parts of its
      phenotype are genetically predisposed. Several single-nucleotide polymorphisms
      (SNPs) have been validated as predisposing to BE but the inherent flaws in the
      trial sizes, presence of controls and statistical power need circumspect
      analysis. The current paper links the interleukin 18 cytokine with BE and perhaps
      EA. Setting aside the issues above there are other issues such as the functional
      relevance of these SNPs for the association BE. There have been several case
      control series published indicating other genes. Furthermore, there are some
      sibling pairs study results with another set of genes identified. Invariably as
      useful as these studies are the size, scale to answer complex questions
      (complexity) and potential clinical significance are proportional in genomic
      studies. The new era of large-scale genome-wide studies in Barrett's and EA is
      needed. Shortly the first will be published showing two SNPs of significance in
      7,838 Barrett's patients.

PMID- 22951877
TI  - Is there a role for angiography in patients with obscure overt bleeding?
AB  - Obscure gastrointestinal hemorrhage remains a challenging but uncommon clinical
      scenario. Video capsule endoscopy (VCE) has been recommended as the third
      diagnostic test after normal upper and lower endoscopic examinations. A recent
      randomized controlled trial comparing immediate VCE to angiography demonstrated a
      superior diagnostic yield for VCE compared with angiography. However, long-term
      outcomes, including rebleeding, hospitalization rates, and death, did not differ
      between the two cohorts. Although VCE appears to be superior to other testing
      modalities for overall diagnostic yield, the clinical outcomes ultimately depend
      upon the type of lesion detected. Vascular lesions, mainly small bowel
      angiodysplasia, can be expected to have the highest rates of rebleeding, despite
      endoscopic therapy, and have been associated with the presence of comorbid
      conditions.

PMID- 22951878
TI  - The truth about cigarette smoking and the risk of inflammatory bowel disease.
AB  - The etiology of inflammatory bowel disease (IBD) is generally believed to be
      multifactorial in nature involving both genetic and environmental factors.
      Cigarette smoking has been shown through previous retrospective observational
      studies to be an environmental factor with both positive and negative influences
      in IBD. Smoking increases the risk of developing Crohn's disease (CD) but not the
      risk of ulcerative colitis (UC). Meanwhile smoking cessation increases the risk
      of a UC flare while CD patients are more likely to show a decrease in disease
      severity. Unfortunately, these observational studies cannot control for bias the
      way a randomized controlled trial can, however, they still reveal meaningful
      truths about smoking and IBD. The study by Higuchi et al. (1) adds to our
      understanding of the impact of smoking on IBD in several ways. They showed that
      increasing exposure to smoking is associated with an increased risk of developing
      CD. They also showed that the risk of UC is highest in the first 2-5 years after
      smoking cessation but remains elevated for > 20 years. This research also raises
      several new issues regarding the association between smoking and IBD, which
      hopefully will be answered through future well-designed observational studies.

PMID- 22951879
TI  - What to take from TREAT?
AB  - The TREAT Registry is an updated submission of the 5-year follow-up of Crohn's
      disease patients from community and academic centers in North America treated
      with or without infliximab. Over 6,000 patients were followed for risks of
      mortality and serious infections. Similar to data presented after nearly 2 years
      of follow-up, mortality was similar for infliximab- and other-treatment-only
      patients. Infliximab, corticosteroids and narcotics were associated with
      increased risks of serious infections. Data presented is similar from data
      reported for controlled trials and observational series in patients with
      inflammatory bowel disease and rheumatoid arthritis.

PMID- 22951881
TI  - Saccharomyces boulardii and antibiotic-associated diarrhea: effectiveness of
      prophylactic use.

PMID- 22951882
TI  - Time to consider medical therapy for small-bowel angioectasias.

PMID- 22951883
TI  - Risk of melanoma in patients who receive thiopurines for inflammatory bowel
      disease is not increased.

PMID- 22951884
TI  - A novel use of rectal swab to test for Clostridium difficile infection by real
      time PCR.

PMID- 22951885
TI  - Actively bleeding dieulafoy lesion identified in a critically ill patient only
      after the use of hydrogen peroxide.

PMID- 22951886
TI  - EUS-Guided Fine-Needle Aspiration of Solid Masses With or Without On-Site
      Cytological Evaluation: No Paradox.

PMID- 22951890
TI  - Higher fibroblast growth factor-23 increases the risk of all-cause and
      cardiovascular mortality in the community.
AB  - Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been
      linked to cardiovascular disease in chronic kidney disease. As community-based
      data of the longitudinal association between FGF23 and cardiovascular events are
      lacking, we investigated a possible relationship in 727 men of the Uppsala
      Longitudinal Study of Adult Men population-based cohort (mean age 77 years).
      During a median follow-up of 9.7 years, 110 participants died of cardiovascular
      causes. In Cox regression models adjusted for age and established cardiovascular
      risk factors, higher serum FGF23 was associated with a significantly increased
      risk for cardiovascular mortality (hazard ratio (HR) per increased s.d. of 1.36).
      This relationship remained significant, albeit attenuated, after adjustment for
      glomerular filtration rate (GFR) (HR 1.21). FGF23 was also associated with all
      cause mortality, although the association was weaker than that with
      cardiovascular mortality, and it was nonsignificant in fully adjusted
      multivariate models. Spline analysis suggested a log-linear relationship between
      FGF23 and outcome. Participants with a combination of high FGF23 (>60 pg/ml), low
      GFR (<60 ml/min), and micro-/macro-albuminuria (albumin/creatinine ratio above 3
      mg/ml) had an almost eightfold increased risk compared with participants without
      these abnormalities. Thus, a higher FGF23 level is associated with an increased
      cardiovascular mortality risk in the community. Clinical trials are needed to
      determine whether FGF23 is a modifiable risk factor.

PMID- 22951891
TI  - The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in
      mesangial cells is associated with glomerular damage in IgA nephropathy.
AB  - IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has
      significant morbidity and mortality as 20-40% of patients progress to end-stage
      renal disease within 20 years of onset. In order to gain insight into the
      molecular mechanisms involved in the progression of IgAN, we systematically
      evaluated renal biopsies from such patients. This showed that the MAPK/ERK
      signaling pathway was activated in the mesangium of patients presenting with over
      1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens
      of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not
      associated with elevated galactose-deficient IgA1 or IgG specific for galactose
      deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation
      through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine
      secretion and was induced by large-molecular-mass IgA1-containing circulating
      immune complexes purified from patient sera. Moreover, IgA1-dependent ERK
      activation required renin-angiotensin system as its blockade was efficient in
      reducing proteinuria in those patients exhibiting substantial mesangial
      activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk,
      leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in
      diagnostic renal biopsies may predict the therapeutic efficacy of renin
      angiotensin system blockers in IgAN.

PMID- 22951894
TI  - A biocompatible flow chamber to study the hemodynamic performance of prosthetic
      heart valves.
AB  - The goal of this study was to design, fabricate, and characterize a biocompatible
      flow chamber to study the performance of artificial heart valves. The system
      consists of a testing fluid chamber and a water chamber (separated by a latex
      diaphragm), following the design of a left ventricular assist device. Two St.
      Jude bileaflet mechanical heart valves were placed oppositely in the testing
      fluid chamber to control flow direction. The flow rate of the testing fluid
      chamber was set at 5.6 L/min, with a stroke volume of 80 ml. The performance of
      the system was examined through three-dimensional numerical simulation and in
      vitro experiments with whole blood and washed platelets. Hemolysis was measured
      with whole blood using a spectrophotometer. Platelet activation was measured by
      platelet surface P-selectin expression using flow cytometry. The three
      dimensional computational fluid dynamics model demonstrated that the flow field
      in the chamber was laminar and physiological. Results from in vitro experiments
      indicated that the flow conditions in the chamber did not induce hemolysis or
      platelet activation with the presence of St. Jude heart valves. Overall, the flow
      chamber can provide a feasible environment to study the hemodynamic performance
      of artificial heart valves.

PMID- 22951892
TI  - Genome-wide association analysis of imputed rare variants: application to seven
      common complex diseases.
AB  - Genome-wide association studies have been successful in identifying loci
      contributing effects to a range of complex human traits. The majority of
      reproducible associations within these loci are with common variants, each of
      modest effect, which together explain only a small proportion of heritability. It
      has been suggested that much of the unexplained genetic component of complex
      traits can thus be attributed to rare variation. However, genome-wide association
      study genotyping chips have been designed primarily to capture common variation,
      and thus are underpowered to detect the effects of rare variants. Nevertheless,
      we demonstrate here, by simulation, that imputation from an existing scaffold of
      genome-wide genotype data up to high-density reference panels has the potential
      to identify rare variant associations with complex traits, without the need for
      costly re-sequencing experiments. By application of this approach to genome-wide
      association studies of seven common complex diseases, imputed up to publicly
      available reference panels, we identify genome-wide significant evidence of rare
      variant association in PRDM10 with coronary artery disease and multiple genes in
      the major histocompatibility complex (MHC) with type 1 diabetes. The results of
      our analyses highlight that genome-wide association studies have the potential to
      offer an exciting opportunity for gene discovery through association with rare
      variants, conceivably leading to substantial advancements in our understanding of
      the genetic architecture underlying complex human traits. 

PMID- 22951895
TI  - Substitution-free hemodiafiltration.
AB  - Hemodiafiltration (HDF) has been reported to deliver better dialysis outcomes in
      patients with end-stage renal disease. Technical advances now allow online-based
      HDF to be used on a clinical basis. However, HDF is being performed at a limited
      rate because of the requirement of exogenous fluid infusion, which causes safety
      and cost issues. Therefore, various modifications on HDF strategies have been
      devised to achieve the HDF without exogenous fluid infusion, which can be
      achieved by spontaneous fluid reinfusion. In this article, substitution-free HDF
      strategies are reviewed in detail, with specific attention to technical aspects
      of the methodology, in vivo and in vitro efficacies, and applicability to
      clinical use.

PMID- 22951896
TI  - Expeditious and less traumatic explantation of a heartware LVAD after myocardial
      recovery.
AB  - After 169 days on left ventricular assist device (LVAD) support, a 62-year-old
      male patient suffering from idiopathic dilatative cardiomyopathy showed signs of
      left ventricular recovery. Off-pump trials were done, and our explantation
      criteria were met. The LVAD removal procedure was performed after 338 days on the
      device, using a left lateral thoracotomy in the sixth intercostal space. First,
      the outflow graft was transected and the distal end was sewed. Then, the pump was
      replaced by an individually manufactured titanium plug. Finally, the driveline
      was cut so that the device could be completely withdrawn. The rest of the
      driveline was accessed through a small abdominal incision and explanted through
      the percutaneous exit site.

PMID- 22951897
TI  - Water oxidation using a particulate BaZrO3-BaTaO2N solid-solution photocatalyst
      that operates under a wide range of visible light.
AB  - Tripping the light fantastic: Despite small band gap energies (1.7-1.8 eV),
      BaZrO(3)-BaTaO(2)N solid solutions (Zr/Ta<=0.1) are capable of photocatalyzing
      both water oxidation and reduction even under irradiation above 660 nm. Solar
      water splitting to form H(2) and O(2) was also demonstrated using a
      photoelectrochemical cell consisting of a BaZrO(3)-BaTaO(2)N solid solution as an
      anode and a Pt wire cathode.

PMID- 22951893
TI  - Nucleic acid aptamers: an emerging frontier in cancer therapy.
AB  - The last two decades have witnessed the development and application of nucleic
      acid aptamers in a variety of fields, including target analysis, disease therapy,
      and molecular and cellular engineering. The efficient and widely applicable
      aptamer selection, reproducible chemical synthesis and modification, generally
      impressive target binding selectivity and affinity, relatively rapid tissue
      penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal
      recognition elements for use as therapeutics or for in vivo delivery of
      therapeutics. In this feature article, we discuss the development and biomedical
      application of nucleic acid aptamers, with emphasis on cancer cell aptamer
      isolation, targeted cancer therapy, oncology biomarker identification and drug
      discovery.

PMID- 22951898
TI  - How is the anionic tetrahedral intermediate involved in the isomerization of
      aspartyl peptides to iso-aspartyl ones? A DFT study on the tetra-peptide.
AB  - An isomerization reaction of a tetra-peptide, Ac-Gly-Asp-Gly-Gly-NHMe -> Ac-Gly
      isoAsp-Gly-Gly-NHMe, was investigated by DFT calculations. Thirteen water
      molecules were added to the peptide for simulating proton transfers during the
      isomerization. As a starting analysis, the number (m) of water molecules
      participating in ready proton transfers was examined by the use of a small model
      system, H(3)C-NH-C(=O)-CH(2)-CH(2)-COOH and (H(2)O)(m). The m = 2 stepwise path
      was found to be of the smallest activation free energy. On the basis of this
      result, the first isomerization path of the tetra-peptide was obtained with four
      elementary processes. The m = 2 proton-transfer pattern is involved in them. A
      different proton transfer gives the second isomerization path with six elementary
      processes. The second path (with ionization) is more likely than the first one
      (without ionization). Formation of the five membered rings of the
      aminosuccinimidyl-residue and anionic tetrahedral intermediates enhances the
      encapsulation of H(3)O(+) through the wound tetra-peptide ring. The role of the
      hydrogen bonds on the encapsulation was discussed in terms of the optimized
      geometries of proton-transfer transition states and intermediates.

PMID- 22951888
TI  - Genetic modulation of lipid profiles following lifestyle modification or
      metformin treatment: the Diabetes Prevention Program.
AB  - Weight-loss interventions generally improve lipid profiles and reduce
      cardiovascular disease risk, but effects are variable and may depend on genetic
      factors. We performed a genetic association analysis of data from 2,993
      participants in the Diabetes Prevention Program to test the hypotheses that a
      genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated
      single-nucleotide polymorphisms modifies the effects of lifestyle and/or
      metformin interventions on lipid levels and nuclear magnetic resonance (NMR)
      lipoprotein subfraction size and number. Twenty-three loci previously associated
      with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1 * 10(-17)).
      Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid
      profile correlated with the GRS (partial |r| = 0.07-0.17, P = 5 * 10(-5)-1 10(
      19)). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol
      levels (beta = +0.87, SEE +/- 0.22 mg/dl/allele, P = 8 * 10(-5), P(interaction) =
      0.02) in the lifestyle intervention group, but not in the placebo (beta = +0.20,
      SEE +/- 0.22 mg/dl/allele, P = 0.35) or metformin (beta = -0.03, SEE +/- 0.22
      mg/dl/allele, P = 0.90; P(interaction) = 0.64) groups. Similarly, a higher GRS
      predicted a greater number of baseline-adjusted small LDL particles at 1 year in
      the lifestyle intervention arm (beta = +0.30, SEE +/- 0.012 ln nmol/L/allele, P =
      0.01, P(interaction) = 0.01) but not in the placebo (beta = -0.002, SEE +/- 0.008
      ln nmol/L/allele, P = 0.74) or metformin (beta = +0.013, SEE +/- 0.008
      nmol/L/allele, P = 0.12; P(interaction) = 0.24) groups. Our findings suggest that
      a high genetic burden confers an adverse lipid profile and predicts attenuated
      response in LDL-C levels and small LDL particle number to dietary and physical
      activity interventions aimed at weight loss.

PMID- 22951899
TI  - A strategy to enhance the binding affinity of fluorophore-aptamer pairs for RNA
      tagging with neomycin conjugation.
AB  - Fluorogenic sulforhodamine-neomycin conjugates have been designed and synthesized
      for RNA tagging. Conjugates were fluorescently activated by binding to RNA
      aptamers and exhibited greater than 250-400 fold enhancement in binding affinity
      relative to corresponding unconjugated fluorophores.

PMID- 22951900
TI  - In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared
      region.
AB  - Hits the dot: Ag(2)S quantum dots (QDs) with bright near-infrared-II fluorescence
      emission (around 1200 nm) and six-arm branched PEG surface coating were
      synthesized for in vivo small-animal imaging. The 6PEG-Ag(2)S QDs afforded a
      tumor uptake of approximately 10 % injected dose/gram, owing to a long
      circulation half-life of approximately 4 h. Clearance of the injected 6PEG-Ag(2)S
      QDs occurs mainly through the biliary pathway in mice.

PMID- 22951901
TI  - Cyclic AMP, protein kinase A, and phosphodiesterases: proceedings of an
      international workshop.
AB  - Cyclic nucleotides cAMP and cGMP are part of almost all major cellular signaling
      pathways. Phosphodiesterases (PDEs) are enzymes that regulate the intracellular
      levels of cAMP and cGMP. Protein kinase A or cAMP-dependent protein kinase
      mediates most cAMP effects in the cell. Over the last 25 years, various
      components of this group of molecules have been involved in human diseases, both
      genetic and acquired. Lately, the PDEs attract more attention. The
      pharmacological exploitation of the PDE's ability to regulate cGMP and cAMP, and
      through them, a variety of signaling pathways, has led to a number of new drugs
      for diverse applications from the treatment of erectile dysfunction to heart
      failure, asthma, and chronic obstructive pulmonary disease. We present the
      abstracts (available online) and selected articles from the proceedings of a
      meeting that took place at the National Institutes of Health (NIH), Bethesda, MD,
      June 8-10, 2011.

PMID- 22951902
TI  - Prkar1a in the regulation of insulin secretion.
AB  - The incidence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide
      with significant consequences on individual quality of life as well as economic
      burden on states' healthcare costs. While origins of the pathogenesis of T2DM are
      poorly understood, an early defect in glucose-stimulated insulin secretion (GSIS)
      from pancreatic beta-cells is considered a hallmark of T2DM. Upon a glucose
      stimulus, insulin is secreted in a biphasic manner with an early first-phase
      burst of insulin, which is followed by a second, more sustained phase of insulin
      output. First phase insulin secretion is diminished early in T2DM as well is in
      subjects who are at risk of developing T2DM. An effective treatment of T2DM with
      incretin hormone glucagon-like peptide-1 (GLP-1) or its long acting peptide
      analogue exendin-4 (E4), restores first-phase and augments second-phase glucose
      stimulated insulin secretion. This effect of incretin action occurs within
      minutes of GLP-1/E4 infusion in T2DM humans. An additional important
      consideration is that incretin hormones augment GSIS only above a certain glucose
      threshold, which is slightly above the normal glucose range. This ensures that
      incretin hormones stimulate GSIS only when glucose levels are high, while they
      are ineffective when insulin levels are below a certain threshold. Activation of
      the GLP-1 receptor, which is highly expressed on pancreatic beta-cells,
      stimulates 2 -distinct intracellular signaling pathways: a) the cAMP-protein
      kinase A branch and b) the cAMP-EPAC2 (EPAC=exchange protein activated by cAMP)
      branch. While the EPAC2 branch is considered to mediate GLP-1 effects on first
      phase GSIS, the PKA branch is necessary for the former branch to be active.
      However, how these 2 branches interplay and converge and how their effects on
      insulin secretion and insulin vesicle exocytosis are coordinated is poorly
      understood.Thus, at the outset of our studies we have a poorly understood
      intracellular interplay of cAMP-dependent signaling pathways, which - when
      stimulated - restore glucose-dependent first phase and augment second phase
      insulin secretion in the ailing beta-cells of T2DM.

PMID- 22951904
TI  - Chondrosarcoma of the tongue: a case report and a review of the literature.
AB  - Chondrosarcoma of the head and neck is uncommon and reported to constitute
      between 1% to 12% of all chondrosarcoma cases.1, 2, 3 Extraskeletal
      chondrosarcoma of the tongue is an extremely rare type of neoplasm with only
      three previously reported cases. The underlying origin of chondrosarcoma arising
      in the tongue is controversial. We describe a case of a low-grade chondrosarcoma
      arising in the base of the tongue of a 54-year-old woman with a central area of
      dedifferentiation. The patient was treated with complete surgical resection with
      no evidence of recurrence at 1 year follow-up.

PMID- 22951903
TI  - Cardiac cyclic nucleotide phosphodiesterases: function, regulation, and
      therapeutic prospects.
AB  - The second messengers cAMP and cGMP exist in multiple discrete compartments and
      regulate a variety of biological processes in the heart. The cyclic nucleotide
      phosphodiesterases, by catalyzing the hydrolysis of cAMP and cGMP, play crucial
      roles in controlling the amplitude, duration, and compartmentalization of cyclic
      nucleotide signaling. Over 60 phosphodiesterase isoforms, grouped into 11
      families, have been discovered to date. In the heart, both cAMP- and cGMP
      hydrolyzing phosphodiesterases play important roles in physiology and pathology.
      At least 7 of the 11 phosphodiesterase family members appear to be expressed in
      the myocardium, and evidence supports phosphodiesterase involvement in regulation
      of many processes important for normal cardiac function including pacemaking and
      contractility, as well as many pathological processes including remodeling and
      myocyte apoptosis. Pharmacological inhibitors for a number of phosphodiesterase
      families have also been used clinically or preclinically to treat several types
      of cardiovascular disease. In addition, phosphodiesterase inhibitors are also
      being considered for treatment of many forms of disease outside the
      cardiovascular system, raising the possibility of cardiovascular side effects of
      such agents. This review will discuss the roles of phosphodiesterases in the
      heart, in terms of expression patterns, regulation, and involvement in
      physiological and pathological functions. Additionally, the cardiac effects of
      various phosphodiesterase inhibitors, both potentially beneficial and
      detrimental, will be discussed.

PMID- 22951908
TI  - Glutathione peroxidase 1 activity dictates the sensitivity of glioblastoma cells
      to oxidative stress.
AB  - The high intratumoral and intertumoral heterogeneity of glioblastoma (GBM) leads
      to resistance to different therapies, and hence, selecting an effective therapy
      is very challenging. We hypothesized that the antioxidant enzyme status is a
      significant feature of GBM heterogeneity. The most important reactive
      oxygen/nitrogen species (ROS/RNS) detoxification mechanisms include superoxide
      dismutase (SOD), catalase, and glutathione peroxidase (GPx). Expression and
      activity of these enzymes and the cellular response to induced oxidative stress
      were systematically analyzed and compared between GBM cells and nontransformed
      glial cells of both human and murine origin. Regardless of cell type or species,
      all tested cells expressed similar amount of catalase and MnSOD. All except one,
      GBM cell lines exhibited a deficiency in GPx1 expression and activity. Analysis
      of GBM tissue sections indicated a heterogeneous profile of weak to moderate
      expression of GPx1 in tumor cells. GPx1 deficiency led to an accumulation of
      ROS/RNS and subsequent death of GBM cells after induction of oxidative stress.
      Astrocytes, microglia/macrophages, and glioma stem cell lines expressed active
      GPx1 and resisted ROS/RNS-mediated cell death. Pharmacological inhibition or
      siRNA silencing of GPx1 partially reverted this resistance in astrocytes,
      indicating the contribution of various antioxidant molecules besides GPx1. The
      GPx1-expressing GBM cell line on the contrary, became extremely sensitive to
      oxidative stress after GPx1 inhibition. Altogether, these results highlight GPx1
      as a crucial element over other antioxidant enzymes for oxidative stress
      regulation in GBM cells. Mapping the antioxidant enzyme status of GBM may prove
      to be a useful tool for personalized ROS/RNS inducing therapies.

PMID- 22951910
TI  - Corneal angiogenesis and lymphangiogenesis.
AB  - PURPOSE OF REVIEW: The purpose of the present review is to describe new
      antilymphangiogenic treatment strategies and recent findings on strain-dependency
      of corneal lymphangiogenesis and the interdependency between blood and lymphatic
      vessel growth. RECENT FINDINGS: Studies on mice have revealed that apart from
      haemangiogenesis, lymphangiogenesis can also differ markedly between several
      mouse strains under normal and inflammatory conditions. Although haemangiogenesis
      and lymphangiogenesis are closely interconnected in their spatial-temporal
      patterning, recent data suggest that they can also occur independently. SUMMARY:
      Understanding the coordinated regulation of blood and lymphatic vessel growth and
      genetic factors determining lymphangiogenesis in more detail could improve the
      development of specifically targeted antihaemangiogenic or antilymphangiogenic
      strategies.

PMID- 22951907
TI  - Astrocytic CX43 hemichannels and gap junctions play a crucial role in development
      of chronic neuropathic pain following spinal cord injury.
AB  - Chronic neuropathic pain is a frequent consequence of spinal cord injury (SCI).
      Yet despite recent advances, upstream releasing mechanisms and effective
      therapeutic options remain elusive. Previous studies have demonstrated that SCI
      results in excessive ATP release to the peritraumatic regions and that purinergic
      signaling, among glial cells, likely plays an essential role in facilitating
      inflammatory responses and nociceptive sensitization. We sought to assess the
      role of connexin 43 (Cx43) as a mediator of CNS inflammation and chronic pain. To
      determine the extent of Cx43 involvement in chronic pain, a weight-drop SCI was
      performed on transgenic mice with Cx43/Cx30 deletions. SCI induced robust and
      persistent neuropathic pain including heat hyperalgesia and mechanical allodynia
      in wild-type control mice, which developed after 4 weeks and was maintained after
      8 weeks. Notably, SCI-induced heat hyperalgesia and mechanical allodynia were
      prevented in transgenic mice with Cx43/Cx30 deletions, but fully developed in
      transgenic mice with only Cx30 deletion. SCI-induced gliosis, detected as
      upregulation of glial fibrillary acidic protein in the spinal cord astrocytes at
      different stages of the injury, was also reduced in the knockout mice with
      Cx43/Cx30 deletions, when compared with littermate controls. In comparison, a
      standard regimen of post-SCI treatment of minocycline attenuated neuropathic pain
      to a significantly lesser degree than Cx43 deletion. These findings suggest Cx43
      is critically linked to the development of central neuropathic pain following
      acute SCI. Since Cx43/Cx30 is expressed by astrocytes, these findings also
      support an important role of astrocytes in the development of chronic pain.

PMID- 22951905
TI  - Phospho-DeltaNp63alpha/SREBF1 protein interactions: bridging cell metabolism and
      cisplatin chemoresistance.
AB  - Tumor protein (TP)-p53 family members (TP63, TP63 and TP73) are guardians of the
      genome and key players in orchestrating the cellular response to cisplatin
      treatment. Cisplatin-induced phosphorylation of DeltaNp63alpha was shown to have
      a role in regulating intracellular DeltaNp63alpha protein levels. We previously
      found that squamous cell carcinoma (SCC) cells exposed to cisplatin displayed the
      ATM-dependent phosphorylation of DeltaNp63alpha (p-DeltaNp63alpha), which is
      critical for the transcriptional regulation of specific downstream mRNAs and
      microRNAs and is likely to underlie the chemoresistance of SCC cells. However,
      SCC cells expressing non-p-DeltaNp63alpha became more cisplatin-resistant. We
      also found that p-DeltaNp63alpha forms complexes with a number of proteins
      involved in cell death response through regulation of cell cycle arrest,
      apoptosis, autophagy, RNA splicing and chromatin modifications. Here, we showed
      that p-DeltaNp63alpha induced ARG1, GAPDH, and CPT2 gene transcription in
      cisplatin-sensitive SCC cells, while non-p-DeltaNp63alpha increased a
      transcription of CAD, G6PD and FASN genes in cisplatin-resistant SCC cells. We
      report that the p-DeltaNp63alpha-dependent regulatory mechanisms implicated in
      the modulation of plethora of pathways, including amino acid, carbohydrate, lipid
      and nucleotide metabolisms, thereby affect tumor cell response to cisplatin
      induced cell death, suggesting that the ATM-dependent DeltaNp63alpha pathway
      plays a role in the resistance of tumor cells to platinum therapy.

PMID- 22951911
TI  - Guidelines change the diagnostic process of cow milk food allergy:  problem-based
      learning.
AB  - PURPOSE OF REVIEW: The accurate diagnosis of food allergy and its management has
      been the subject of two published guidelines, the National Institute of Health
      Sponsored Expert Panel Guidelines and the World Allergy Organization guidelines:
      Diagnosis and Rationale for Action Against Cow Milk Allergy. Both guidelines have
      drawn attention to the unique aspects of different food allergens. They have
      highlighted the possible overdiagnosis and underdiagnosis of food allergy. The
      purpose of this review is to demonstrate the utility and application of the two
      published guidelines in a real-life scenario that the pediatrician or
      allergy/immunology specialist may be faced with. RECENT FINDINGS: This review is
      divided into two sections: the first section is problem-based learning,
      presenting a clinical scenario of a child suspected of cow milk allergy (CMA) and
      followed over time. At each step, the guidelines are consulted and referenced.
      The second section reviews recent research that demonstrates that CMA has a high
      prevalence, and that testing methodologies can be improved on. SUMMARY:
      Clinicians taking the approach outlined by the guidelines will be able to confirm
      or refute a diagnosis of CMA, all the while minimizing unnecessary tests and
      procedures.

PMID- 22951913
TI  - Generation of controllable gradients in cell density.
AB  - Making the grad(ient): a gradient in cell density was generated on a substrate
      that was inserted into a homogeneous suspension of cells at a specific tilt angle
      by taking advantage of the gradual change in the number of cells available for
      sedimentation. Reverse gradients were also fabricated on the same substrate using
      multiple sedimentation procedures.

PMID- 22951914
TI  - Local mononuclear cell infiltrates in infertile patients with endometrial
      macropolyps versus micropolyps.
AB  - STUDY QUESTION: Is the endometrial mononuclear cell population in infertile
      patients altered in subjects with classical endometrial polyps (macropolyps)
      versus endometrial micropolyps that are hysteroscopically recognized as small
      uterine cavity protrusions? SUMMARY ANSWER: Macropolypoid endometrium had a low
      density of pan-leukocytes, pan-T cells and natural killer (NK) cells, whereas
      micropolypoid endometrium was characterized by high density of B cells and
      plasmacytes, along with a low density of NK cells. WHAT IS KNOWN ALREADY:
      Endometrial micropolyps co-exist at a high rate with chronic endometritis, which
      is an unusual plasmacyte infiltration within the endometrial stromal compartment.
      STUDY DESIGN: Prospective cross-sectional study. From July 2009 to June 2011,
      hysteroscopy was performed for infertile women who had been suspected for
      endometrial macropolyps and who had repeated in vitro fertilization-embryo
      transfer failure over three or more cycles. Endometrial biopsy samples were
      obtained from the patients with macropolyps or micropolyps during the
      proliferative phase. Of 137 patients assessed, 30 were diagnosed with endometrial
      macropolyps and 34 were diagnosed with endometrial micropolyps. After the
      exclusion of the cases with heavy uterine bleeding, potential neoplasms,
      submucosal uterine fibroids, uterine septa, and/or intrauterine adhesion, 23
      patients with macropolypoid endometrium; 25 patients with micropolypoid
      endometrium and 27 patients with non-polypoid endometrium were enrolled in the
      study. Endometrial macropolyps were surgically removed, whereas chronic
      endometritis was treated with antibiotics. The patients were followed up until
      December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The paraformaldehyde
      fixed paraffin-embedded endometrial sections were immunostained with monoclonal
      antibodies against the specific markers of pan-leukocytes (CD45), pan-T cells
      (CD3), Th cells (CD4), Tc cells (CD8), B cells (CD20), plasmacytes (CD138), NK
      cells (CD56) and macrophages (CD68). The immunoreactive cells were enumerated in
      at least 20 non-overlapping stromal areas. MAIN RESULTS AND THE ROLE OF CHANCE:
      Compared with the non-polypoid endometrium, macropolypoid endometrium contained a
      lower density of pan-leukocytes, pan-T cells and NK cells, whereas micropolypoid
      endometrium had a higher density of pan-leukocytes and B cells, along with a
      lower density of NK cells. Following the treatments, 10 patients with
      macropolypoid endometrium, 11 patients with micropolypoid endometrium and 10
      patients with non-polypoid endometrium conceived. LIMITATIONS, REASONS FOR
      CAUTION: One potential bias is immunohistochemical enumeration for leukocyte
      density was conducted by one examiner. The limitation of this study is that the
      results relied on endometrial biopsy specimens, of which immunological conditions
      may not always represent those in the whole endometrium. WIDER IMPLICATIONS OF
      THE FINDINGS: There may be some ethnic or racial variances in the composition of
      the endometrial mononuclear cell subsets of infertile women. STUDY
      FUNDING/COMPETING INTEREST(S): This study was supported by Grand-in-Aid for
      Scientific Research from the Ministry of Education, Culture, Sports, Science and
      Technology (22591840). There were no conflicts of interest to declare.

PMID- 22951915
TI  - Altered gene expression profile in cumulus cells of mature MII oocytes from
      patients with polycystic ovary syndrome.
AB  - STUDY QUESTION: Oocyte developmental competence is altered in patients with
      polycystic ovary syndrome (PCOS); is gene expression in cumulus cells (CCs) from
      mature metaphase II oocytes of patients with PCOS altered as well? SUMMARY
      ANSWER: Compared with CCs from non-PCOS patients, the gene expression profile of
      CCs isolated from mature oocytes of patients with PCOS present alterations that
      could explain the abnormal folliculogenesis and reduced oocyte competence in such
      patients. WHAT IS KNOWN ALREADY: Abnormal mRNA expression of several members of
      the insulin-like growth factor (IGF) family in CCs from PCOS patients was
      previously reported. Moreover, the whole transcriptome has been investigated in
      cultured CCs from PCOS patients. STUDY DESIGN, SIZE AND DURATION: This
      retrospective study included six PCOS patients diagnosed following the Rotterdam
      Criteria and six non-PCOS patients who all underwent ICSI for male infertility in
      the assisted reproduction technique (ART) Department of Montpellier University
      Hospital, between 2009 and 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS: CCs
      from PCOS and non-PCOS patients who underwent controlled ovarian stimulation
      (COS) were isolated mechanically before ICSI. Gene expression profiles were
      analysed using the microarray technology and the Significance Analysis of
      Microarray was applied to compare the expression profiles of CCs from PCOS and
      non-PCOS patients. MAIN RESULTS: The gene expression profile of CCs from patients
      with PCOS was significantly different from that of CCs from non-PCOS patients.
      Specifically, CCs from women with PCOS were characterized by abnormal expression
      of many growth factors, including members of the epidermal growth factor-like
      (EGFR, EREG and AREG) and IGF-like families (IGF1R, IGF2R, IGF2BP2 and IGFBP2),
      that are known to play a role in oocyte competence. In addition, mRNA transcripts
      of factors involved in steroid metabolism, such as CYP11A1, CYP1B1, CYP19A1 and
      CYP2B7P1, were deregulated in PCOS CCs, and this could explain the abnormal
      steroidogenesis observed in these women. Functional annotation of the
      differentially expressed genes suggests that defects in the transforming growth
      factor beta and estrogen receptors signalling cascades may contribute to the
      reduced oocyte developmental competence in patients with PCOS. LIMITATIONS AND
      REASONS FOR CAUTION: Owing to the strict selection criteria (similar age, weight
      and reasons for ART), this study included a small sample size (six cases and six
      controls), and thus, further investigations using a large cohort of patients are
      needed to confirm these results. WIDER IMPLICATIONS OF THE FINDINGS: This study
      opens a new perspective for understanding the pathogenesis of PCOS. STUDY
      FUNDING/COMPETING INTERESTS: This work was partially supported by a grant from
      the Ferring Pharmaceutical. The authors of the study have no competing interests
      to report. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 22951916
TI  - Unnatural amino acid mutagenesis of fluorescent proteins.

PMID- 22951917
TI  - Electron reduction processes of nitrothiophenes. A systematic approach by DFT
      computations, cyclic voltammetry and E-ESR spectroscopy.
AB  - In the framework of the interest in nitrothiophenes as drugs or hits with
      different pharmacological applications and considering that in several instances
      nitroreduction is an essential step for their biological activity, we have
      studied a complete series of mono-, di-, and tri-nitrothiophenes (1-6) and by
      comparison some mononitro benzo[b]thiophenes and benzo[b]furans (7-10). Their
      electroreduction behaviour has been investigated by different techniques: DFT
      calculations, cyclic voltammetry and electrochemical electron spin resonance
      spectroscopy. Although, the first reduction process for all of the compounds
      leads to the relevant radical anions, both the computational and experimental
      results indicate that there are significant differences in the fate of their
      corresponding forthcoming reductions, for example, formation of secondary
      radicals (open-shell electronic structures) or dianions. The effect of the
      relative positions of the nitro groups during the reduction has also been
      analysed and rationalised.

PMID- 22951918
TI  - Generation of tissue constructs for cardiovascular regenerative medicine: from
      cell procurement to scaffold design.
AB  - The ability of the human body to naturally recover from coronary heart disease is
      limited because cardiac cells are terminally differentiated, have low
      proliferation rates, and low turn-over rates. Cardiovascular tissue engineering
      offers the potential for production of cardiac tissue ex vivo, but is currently
      limited by several challenges: (i) Tissue engineering constructs require pure
      populations of seed cells, (ii) Fabrication of 3-D geometrical structures with
      features of the same length scales that exist in native tissue is non-trivial,
      and (iii) Cells require stimulation from the appropriate biological, electrical
      and mechanical factors. In this review, we summarize the current state of
      microfluidic techniques for enrichment of subpopulations of cells required for
      cardiovascular tissue engineering, which offer unique advantages over traditional
      plating and FACS/MACS-based enrichment. We then summarize modern techniques for
      producing tissue engineering scaffolds that mimic native cardiac tissue. 

PMID- 22951920
TI  - Herb-drug interactions.

PMID- 22951921
TI  - DMA Clinical Pilates Directional-Bias Assessment: Reliability and Predictive
      Validity.
AB  - STUDY DESIGN: Randomized, repeated-measures crossover design. OBJECTIVES: To
      determine the interrater reliability of directional-bias assessment and to
      investigate its validity for predicting immediate changes in dynamic postural
      stability and muscle performance following directionally biased exercises.
      BACKGROUND: Directional bias in dynamic postural stability deficits may be
      associated with outcome following intervention. METHODS: Two researchers
      independently assessed 33 participants, each with a history of more than 1
      unilateral lower-limb injury, for directional bias. Interrater reliability was
      evaluated with the kappa coefficient and a prevalence-adjusted and bias-adjusted
      kappa coefficient. Participants were randomly allocated to perform matched-bias
      (MB) or unmatched-bias (UB) exercises first, in 2 crossover groups. Two outcome
      measures, time to stabilization and rebound hopping, were assessed before and
      following each exercise intervention, using a force plate. Crossover trial data
      were analyzed by t tests for period, interaction, and treatment effects, and
      repeated-measures analyses of variance were used to investigate differences
      between baseline, MB, and UB. RESULTS: Interrater reliability of directional-bias
      assessment was substantial (kappa = 0.75; prevalence-adjusted and bias-adjusted
      kappa = 0.76). Following MB exercises, medial/lateral time to stabilization and
      time on the ground during rebound hopping were significantly shorter (P = .01 and
      P = .05, respectively) compared with UB exercises. Compared with baseline,
      pairwise change in anterior/posterior time to stabilization (P = .008) improved
      following MB, whereas time in the air decreased following UB (P = .036).
      CONCLUSION: Directional-bias assessment demonstrates substantial reliability, and
      outcomes suggest validity for predicting immediate improvements following matched
      directionally biased exercises.

PMID- 22951922
TI  - Temporal and spatial distribution of waterborne mercury in a gold miner's river.
AB  - We examined the spatial and temporal (hourly) variation of aqueous concentrations
      of mercury in a gold miner's river to determine factors that control transport,
      retention, and export of mercury. The mercury flux was estimated to account for
      episodic inputs of mercury through mining tailings, variations in flow rate, and
      the partitioning of mercury between dissolved and particulate phases. Water
      samples were collected upstream and downstream of two gold mining sites in the
      Artiguas river, Nicaragua. The samples were analyzed for dissolved and suspended
      mercury, total solids, dissolved organic carbon, and total iron in water. Water
      velocity was also measured at the sampling sites. We found that mercury was
      mainly transported in a suspended phase, with a temporal pattern of diurnal peaks
      corresponding to the amalgamation schedules at the mining plants. The
      concentrations decreased with distance from the mining sites, suggesting dilution
      by tributaries or sedimentation of particle-bound mercury. The lowest total
      mercury concentrations in the water were less than 0.1 MUg l(-1) and the highest
      concentration was 5.0 MUg l(-1). The mercury concentrations are below the present
      WHO guidelines of 6 MUg l(-1) but are considered to lead to a higher risk to
      aquatic bacteria and fish in the stream than to humans. The aqueous
      concentrations exceed the hazard endpoints for both groups by a probability of
      about 1%. Particulate mercury accounted for the largest variation of mercury
      fluxes, whereas dissolved mercury made up most of the long-range transport along
      the stream. The estimated total mass of mercury retained due to sedimentation of
      suspended solids was 2.7 kg per year, and the total mass exported downstream from
      the mining area was 1.6 kg per year. This study demonstrates the importance of
      the temporal and spatial resolution of observations in describing the occurrence
      and fate of mercury in a river affected by anthropogenic activities.

PMID- 22951923
TI  - Proton beam therapy: more than a leap of faith?

PMID- 22951924
TI  - WHO's ambitious new European health strategy.

PMID- 22951919
TI  - Shining light on nanotechnology to help repair and regeneration.
AB  - Phototherapy can be used in two completely different but complementary
      therapeutic applications. While low level laser (or light) therapy (LLLT) uses
      red or near-infrared light alone to reduce inflammation, pain and stimulate
      tissue repair and regeneration, photodynamic therapy (PDT) uses the combination
      of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen
      species that can kill infectious microorganisms and cancer cells or destroy
      unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in
      the arteries). The recent development of nanotechnology applied to medicine
      (nanomedicine) has opened a new front of advancement in the field of phototherapy
      and has provided hope for the development of nanoscale drug delivery platforms
      for effective killing of pathological cells and to promote repair and
      regeneration. Despite the well-known beneficial effects of phototherapy and
      nanomaterials in producing the killing of unwanted cells and promoting repair and
      regeneration, there are few reports that combine all three elements i.e.
      phototherapy, nanotechnology and, tissue repair and regeneration. However, these
      areas in all possible binary combinations have been addressed by many workers.
      The present review aims at highlighting the combined multi-model applications of
      phototherapy, nanotechnology and, reparative and regeneration medicine and
      outlines current strategies, future applications and limitations of nanoscale
      assisted phototherapy for the management of cancers, microbial infections and
      other diseases, and to promote tissue repair and regeneration. 

PMID- 22951925
TI  - US lags behind other countries in cutting numbers of preventable deaths.

PMID- 22951926
TI  - BMA warns against any extension of "zero hours" contracts in NHS.

PMID- 22951927
TI  - Autophagy plays a protective role in endoplasmic reticulum stress-mediated
      pancreatic beta cell death.
AB  - There is a growing evidence of the role of autophagy in pancreatic beta cell
      homeostasis. During development of type 2 diabetes, beta cells are required to
      supply the increased demand of insulin. In such a stage, beta cells have to
      address high ER stress conditions that could lead to abnormal insulin secretion,
      and ultimately, beta cell death and overt diabetes. In this study, we used
      insulin secretion-deficient beta cells derived from fetal mice. These cells
      present an increased accumulation of polyubiquitinated protein aggregates and
      LC3B-positive puncta, when compared with insulinoma-derived beta cell lines. We
      found that insulin secretion deficiency renders these cells hypersensitive to
      endoplasmic reticulum (ER) stress-mediated cell death. Chemical or shRNA-mediated
      inhibition of autophagy increased beta cell death under ER stress. On the other
      hand, rapamycin treatment increased both autophagy and cell survival under ER
      stress. Insulin secretion-deficient beta cells showed a marked reduction of the
      antiapoptotic protein BCL2, together with increased BAX expression and ERN1
      hyperactivation upon ER stress induction. These results showed how insulin
      secretion deficiency in beta cells may be contributing to ER stress-mediated cell
      death, and in this regard, we showed how the autophagic response plays a
      prosurvival role.

PMID- 22951928
TI  - Intraventricular injection of FGF-2 promotes generation of oligodendrocyte
      lineage cells in the postnatal and adult forebrain.
AB  - FGF2 is considered a key factor in the generation of oligodendrocytes (OLs)
      derived from neural stem cells (NSCs) located within the subventricular zone
      (SVZ). Here, we have examined FGF2 signaling in the forebrain of postnatal and
      adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ)
      and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these
      microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and FGFR2 are
      enriched in the dSVZ, from which OLs are largely derived, whereas FGFR3 are
      significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly
      generate olfactory interneurons. We show that direct administration of FGF2 into
      the lateral ventricle increased the generation of oligodendrocyte progenitors
      (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and
      ependymal wall of the SVZ. Furthermore, FGF2 stimulated proliferation of neural
      progenitors (NPs) and their differentiation into OPCs. The results indicate that
      FGF2 increased specification of OPCs, inducing NPs to follow an oligodendrocyte
      developmental pathway. Notably, FGF2 did not block OPC differentiation and
      increased the number of oligodendrocytes in the periventricular white matter
      (PVWM) and cortex. However, FGF2 markedly disrupted myelination in the PVWM. A
      key finding was that FGF2 had equivalent actions on the generation of OPCs and
      myelin disruption in postnatal and adult mice. This study demonstrates a central
      role for FGF2 in promoting oligodendrocyte generation in the developing and adult
      brain.

PMID- 22951929
TI  - Deciphering the epigenetic network in colorectal cancer.
AB  - The sequential accumulation of genetic alterations has been classically
      considered responsible for the origin and subsequent progression of colorectal
      cancer, although recent cumulative data provide strong evidence of the
      significance of epigenetic changes in the development of this multi-step
      malignancy. Among the epigenetic alterations, miRNAs deregulation has emerged as
      an exciting and promising field in cancer research. In a recent issue of the
      Journal of Pathology, Wang and colleagues identify miR-149 as being silenced by
      methylation in colorectal cancer. The authors also identified Sp1 as a target of
      miR-149. These intriguing observations have important biological prognostic and
      therapeutic implications.

PMID- 22951930
TI  - ICU-based rehabilitation and its appropriate metrics.
AB  - PURPOSE OF REVIEW: Survival of critically ill patients is frequently associated
      with significant functional impairment and reduced health-related quality of
      life. Early rehabilitation of ICU patients has recently been identified as an
      important focus for interdisciplinary ICU teams. However, the amount of
      rehabilitation performed in ICUs is often inadequate. The scope of the review is
      to discuss recent developments in application of assessment tools and
      rehabilitation in critically ill patients within an interdisciplinary approach.
      RECENT FINDINGS: ICU-based rehabilitation has become an important evidence-based
      component in the management of patients with critical illness. The assessment and
      evidence-based treatment of these patients should include a focus on prevention
      and treatment of deconditioning (muscle weakness, joint stiffness, impaired
      functional performance) and weaning failure (respiratory muscle weakness) to
      identify targets for rehabilitation. A variety of modalities for assessment and
      early ICU rehabilitation are supported by emerging clinical research and must be
      implemented according to the stage of critical illness, comorbidities, and
      consciousness and cooperation of the patient. SUMMARY: Daily evaluation of every
      critically ill patient should include evaluation of the need for bedrest and
      immobility, and assessment of the potential for early rehabilitation
      interventions. Early ICU rehabilitation is an interdisciplinary team
      responsibility, involving physical therapists, occupational therapists, nurses
      and medical staff.

PMID- 22951931
TI  - Isolable phosphanylidene phosphorane with a sterically accessible two-coordinate
      phosphorus atom.

PMID- 22951935
TI  - The role of myringotomy and ventilation tube insertion in maxillary swing
      approach nasopharyngectomy: review of our 10-year experience.
AB  - OBJECTIVES/HYPOTHESIS: The use of myringotomy with ventilation tube insertion
      after maxillary swing nasopharyngectomy was originally described to prevent the
      occurrence of otitis media with effusion. The outcome of this otologic procedure
      has never been reviewed and discussed. The purpose of this study is to examine
      the role of myringotomy with ventilation tube insertion in this group of
      patients. STUDY DESIGN: Retrospective review. METHODS: One hundred forty-two
      patients with maxillary swing nasopharyngectomy were recruited from 1999 to 2008.
      The otologic status was evaluated using otoscopy, pure tone audiogram, and
      tympanogram at 3 months, 6 months, and then yearly after the operation. The
      results were reviewed periodically during that 10-year period. During this
      period, there were three groups; the first group had myringotomy with ventilation
      tube inserted, the second group had myringotomy alone, and the third group had no
      myringotomy performed. RESULTS: There were significantly (P < .0001) more
      patients in the myringotomy with ventilation tube insertion group who suffered
      from adverse otologic complications such as discharging grommet, discharging
      chronic suppurative otitis media, and perforated eardrum when compared with
      patients with myringotomy alone and patients without myringotomy at 3 months, 6
      months, and 12 months. There were no differences in the incidence of acute otitis
      media among all three groups of patients. CONCLUSIONS: Patients who underwent
      maxillary swing nasopharyngectomy and myringotomy with ventilation tube
      insertions suffered from more otologic complications. The routine use of
      myringotomy with or without ventilation tube insertion for this group of patients
      is not recommended.

PMID- 22951932
TI  - Comparative genome analysis of three eukaryotic parasites with differing
      abilities to transform leukocytes reveals key mediators of Theileria-induced
      leukocyte transformation.
AB  - We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan
      protozoan parasite of cattle. The focus of this study was a comparative genome
      analysis of T. orientalis relative to other highly pathogenic Theileria species,
      T. parva and T. annulata. T. parva and T. annulata induce transformation of
      infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T.
      orientalis does not induce uncontrolled proliferation of infected leukocytes and
      multiplies predominantly within infected erythrocytes. While synteny across
      homologous chromosomes of the three Theileria species was found to be well
      conserved overall, subtelomeric structures were found to differ substantially, as
      T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable
      secreted protein-encoding gene family. Moreover, expansion of particular gene
      families by gene duplication was found in the genomes of the two transforming
      Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene
      families that are present only in T. parva and T. annulata and not in T.
      orientalis, Babesia bovis, or Plasmodium were also identified. Identification of
      differences between the genome sequences of Theileria species with different
      abilities to transform and immortalize bovine leukocytes will provide insight
      into proteins and mechanisms that have evolved to induce and regulate this
      process. The T. orientalis genome database is available at
      http://totdb.czc.hokudai.ac.jp/.

PMID- 22951936
TI  - Preparative, in vitro biocatalysis of triketide lactone chiral building blocks.
AB  - PKS biocatalysis: The terminal module of erythromycin synthase was used for the
      in vitro production of chiral triketide lactones. Combining cofactor
      regeneration, substrate truncation, and enzymatic promiscuity afforded a scalable
      strategy to generate these molecules from abundant racemic and achiral
      precursors. The described biocatalytic platform thus facilitates the application
      and study of enzymes within PKS modules.

PMID- 22951933
TI  - Comparative genome analysis of Trichophyton rubrum and related dermatophytes
      reveals candidate genes involved in infection.
AB  - The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or
      fungal pathogen of human skin. To facilitate molecular analyses of the
      dermatophytes, we sequenced T. rubrum and four related species, Trichophyton
      tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum.
      These species differ in host range, mating, and disease progression. The
      dermatophyte genomes are highly colinear yet contain gene family expansions not
      found in other human-associated fungi. Dermatophyte genomes are enriched for gene
      families containing the LysM domain, which binds chitin and potentially related
      carbohydrates. These LysM domains differ in sequence from those in other species
      in regions of the peptide that could affect substrate binding. The dermatophytes
      also encode novel sets of fungus-specific kinases with unknown specificity,
      including nonfunctional pseudokinases, which may inhibit phosphorylation by
      competing for kinase sites within substrates, acting as allosteric effectors, or
      acting as scaffolds for signaling. The dermatophytes are also enriched for a
      large number of enzymes that synthesize secondary metabolites, including
      dermatophyte-specific genes that could synthesize novel compounds. Finally,
      dermatophytes are enriched in several classes of proteases that are necessary for
      fungal growth and nutrient acquisition on keratinized tissues. Despite
      differences in mating ability, genes involved in mating and meiosis are conserved
      across species, suggesting the possibility of cryptic mating in species where it
      has not been previously detected. These genome analyses identify gene families
      that are important to our understanding of how dermatophytes cause chronic
      infections, how they interact with epithelial cells, and how they respond to the
      host immune response.

PMID- 22951937
TI  - [Meeting of experts on obstructive airway diseases: targets and methods].
AB  - New insights into the pathogenesis and clinical course of chronic obstructive
      pulmonary disease (COPD) and asthma have become available. Systematic analyses of
      well-defined and intensively monitored patient cohorts are being published,
      particularly from the ECLIPSE cohort in the U.S.A. and from the network COSYCONet
      in Germany. Important articles from 2011 on COPD and asthma put former concepts
      into question. There is a new understanding of the relationship between
      parenchymal destruction and bronchial obstruction in COPD as well as on the
      impact of cardiovascular comorbidity. Computed tomography allows high-resolution
      imaging of lung structures, and MRI delivers supplementary functional
      information. Researchers have also investigated the value of patient-reported
      outcomes, such as quality of life, dyspnoea, or the COPD assessment test (CAT).
      Members of the GOLD committee are trying to establish a feasible classification
      of the multiple facets of COPD. With respect to treatment, novel data on beta
      adrenergic antagonists in COPD and on muscarinic antagonists in asthma have been
      published. These aspects were discussed during an expert meeting and are now
      summarised in the present review article.

PMID- 22951938
TI  - [Modern treatment of sarcoidosis].

PMID- 22951941
TI  - Vulvar pain: Anatomic and recent pathophysiologic considerations.
AB  - Vulvar pain syndrome or vulvodynia is a common multifactorial, heterogeneous, and
      chronic gynecological disorder with an estimated prevalence of up to 16%. This
      disorder seriously impacts the quality of life of women in several ways. The
      etiology of this condition is complex and remains elusive and requires an
      extensive differential diagnosis. A standard therapeutic approach for the
      management of vulvar pain is still under investigation and must be
      multidisciplinary. This review outlines the anatomic and pathophysiologic aspects
      of vulvar pain.

PMID- 22951942
TI  - Base catalysed synthesis of thiochromans and azo-linked chromenes using
      allenylphosphonates.
AB  - An efficient base catalysed approach to the synthesis of thiochromans/chromenes
      from allenylphosphonates (and an allenoate) and substrates having SH/OH and CHO
      groups at appropriate positions has been developed. Several azo-linked chromenes
      that are bright red pigments are also synthesized. This methodology involves the
      domino reactions of Michael addition and subsequent cyclisation by intramolecular
      aldol reaction.

PMID- 22951943
TI  - Follicular carcinoma of the thyroid with massive invasion into the cervical and
      mediastinum great veins: our own experience and literature review.
AB  - Thyroid carcinomas with massive intralumen invasion of the great veins are
      extremely rare and reported to have poor prognosis. We report a case of a poorly
      differentiated follicular carcinoma of the thyroid with extensive invasion into
      the bilateral internal jugular veins, brachiocephalic vein, and superior vena
      cava. All of the seven major drainage veins from the thyroid were involved by
      tumor thrombus. The patient was successfully treated by surgical resection
      including removal of the tumor thrombus and repair of the great veins. The
      importance of preoperative radiological findings, treatment, and outcome are
      discussed along with a literature review.

PMID- 22951945
TI  - Nitroxide radicals as highly reactive redox mediators in dye-sensitized solar
      cells.

PMID- 22951944
TI  - Hematopoietic stem cell mobilization: updated conceptual renditions.
AB  - Despite its specific clinical relevance, the field of hematopoietic stem cell
      mobilization has received broad attention, owing mainly to the belief that
      pharmacologic stem cell mobilization might provide clues as to how stem cells are
      retained in their natural environment, the bone marrow 'niche'. Inherent to this
      knowledge is also the desire to optimally engineer stem cells to interact with
      their target niche (such as after transplantation), or to lure malignant stem
      cells out of their protective niches (in order to kill them), and in general to
      decipher the niche's structural components and its organization. Whereas, with
      the exception of the recent addition of CXCR4 antagonists to the armamentarium
      for mobilization of patients refractory to granulocyte colony-stimulating factor
      alone, clinical stem cell mobilization has not changed significantly over the
      last decade or so, much effort has been made trying to explain the complex
      mechanism(s) by which hematopoietic stem and progenitor cells leave the marrow.
      This brief review will report some of the more recent advances about
      mobilization, with an attempt to reconcile some of the seemingly inconsistent
      data in mobilization and to interject some commonalities among different
      mobilization regimes.

PMID- 22951946
TI  - Design of a testing strategy using non-animal based test methods: lessons learnt
      from the ACuteTox project.
AB  - In the framework of toxicology, a testing strategy can be viewed as a series of
      steps which are taken to come to a final prediction about a characteristic of a
      compound under study. The testing strategy is performed as a single-step
      procedure, usually called a test battery, using simultaneously all information
      collected on different endpoints, or as tiered approach in which a decision tree
      is followed. Design of a testing strategy involves statistical considerations,
      such as the development of a statistical prediction model. During the EU FP6
      ACuteTox project, several prediction models were proposed on the basis of
      statistical classification algorithms which we illustrate here. The final choice
      of testing strategies was not based on statistical considerations alone. However,
      without thorough statistical evaluations a testing strategy cannot be identified.
      We present here a number of observations made from the statistical viewpoint
      which relate to the development of testing strategies. The points we make were
      derived from problems we had to deal with during the evaluation of this large
      research project. A central issue during the development of a prediction model is
      the danger of overfitting. Procedures are presented to deal with this challenge.

PMID- 22951947
TI  - In vitro models for assessing the potential cardiovascular disease risk
      associated with cigarette smoking.
AB  - Atherosclerotic cardiovascular disease is a prevalent human disorder and a
      significant cause of human morbidity and mortality. A number of risk factors may
      predispose an individual to developing atherosclerosis, and of these factors,
      cigarette smoking is strongly associated with the development of cardiovascular
      disease. Current thinking suggests that exposure to toxicants found in cigarette
      smoke may be responsible for this elevated disease likelihood, and this gives
      rise to the idea that reductions in the levels of some smoke toxicants may reduce
      the harm associated with cigarette smoking. To assess the disease risk of
      individuals who smoke cigarettes with altered toxicant levels, a weight-of
      evidence approach is required examining both exposure and disease-related
      endpoints. A key element of such an assessment framework are data derived from
      the use of in vitro models of cardiovascular disease, which when considered
      alongside other forms of data (e.g. from clinical studies) may support evidence
      of potential reduced risk. Importantly, such models may also be used to provide
      mechanistic insight into the effects of smoking and of smoke toxicant exposure in
      cardiovascular disease development. In this review the use of in vitro models of
      cardiovascular disease and one of the contributory factors, oxidative stress, is
      discussed in the context of assessing the risk potential of both conventional and
      modified cigarettes. Practical issues concerning the use of these models for
      cardiovascular disease understanding and risk assessment are highlighted and
      areas of development necessary to enhance the power and predictive capacity of in
      vitro disease models in risk assessment are discussed.

PMID- 22951948
TI  - Comparative analysis of eight cytotoxicity assays evaluated within the ACuteTox
      Project.
AB  - A comparative analysis of eight cytotoxicity assays [the 3T3 and normal human
      keratinocytes Neutral Red Uptake (NRU) assay, the primary rat hepatocytes, human
      HepG2 and 3T3 MTT assay, and the human A.704, SH-SY5Y and HepG2 cells propidium
      iodide (PI) assay] included in several work packages of the EU Integrated Project
      ACuteTox, has been carried out. The aim was to evaluate whether cells originating
      from liver, kidney and brain provided different in vitro acute toxicity results,
      and the influence of primary liver cells versus cell lines originated from the
      same tissue. Spearman rank correlation analysis and Hierarchical Cluster Analysis
      were performed based on the IC50 (50% inhibitory concentrations for the endpoint
      measured) values generated for 57 chemicals. A relatively large number of
      neurotoxicants and hepatotoxicants were included which allowed to examine the
      impact of chemicals with specific tissue toxicity on the results. Our analyses
      confirmed the similarity between the NRU assays and between the two hepatic cell
      systems related MTT assays. The type of assay appears to have the greatest
      influence upon the clustering result regardless of the origin of the cells used.
      The information provided by the NRU and MTT assays differed from that provided by
      the PI assay. This approach did not allow to show tissue specific toxicity but it
      does reveal the effectiveness of the clustering methodology for choosing assays
      for a testing program for predicting e.g. acute oral toxicity in humans.

PMID- 22951949
TI  - Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the
      intracellular copper level, triggering cytochrome c release and caspase
      activation.
AB  - Dithiocarbamates are nitrogen- and sulfur-containing compounds commonly used in
      pharmacology, medicine and agriculture. The molecular effects of dithiocarbamates
      on neuronal cell systems are not fully understood, especially in terms of their
      ability to accumulate copper ions inside the cell. In this work, the molecular
      effects of N,N-diethyldithiocarbamate (DEDTC) were studied in human SH-SY5Y
      neuroblastoma cells to determine the role of copper in the DEDTC toxicity and the
      pathway trigged in cell by the complex Cu-DEDTC. From concentration-dependent
      studies, we found that 5 MUM of this compound induced a drastic decrease in
      viable cells with a concomitant accumulation in intracellular copper resulted
      from complexation with DEDTC, measured by atomic absorption spectroscopy. The
      mechanism of DEDTC-induced apoptosis in neuronal model cells is thought to occur
      through the death receptor signaling triggered by DEDTC-copper complex in low
      concentration that is associated with the activation of caspase 8. Our results
      indicated that the mechanism of cell death involves cytochrome c release forming
      the apoptosome together with Apaf-1 and caspase 9, converting the caspase 9 into
      its active form, allowing it to activate caspase 3 as observed by
      immunofluorescence. This pathway is induced by the cytotoxic effects that occur
      when DEDTC forms a complex with the copper ions present in the culture medium and
      transports them into the cell, suggesting that the DEDTC by itself was not able
      to cause cell death and the major effect is from its copper-complex in
      neuroblastoma cells. The present study suggests a role for the influence of
      copper by low concentrations of DEDTC in the extracellular media, the absorption
      and accumulation of copper in the cell and apoptotic events, induced by the
      cytotoxic effects that occur when DEDTC forms a complex with the copper ions.

PMID- 22951950
TI  - A step-by-step method for the reconstitution of an ABC transporter into nanodisc
      lipid particles.
AB  - The nanodisc is a discoidal particle (~ 10-12 nm large) that trap membrane
      proteins into a small patch of phospholipid bilayer. The nanodisc is a
      particularly attractive option for studying membrane proteins, especially in the
      context of ligand-receptor interactions. The method pioneered by Sligar and
      colleagues is based on the amphipathic properties of an engineered highly a
      helical scaffold protein derived from the apolipoprotein A1. The hydrophobic
      faces of the scaffold protein interact with the fatty acyl side-chains of the
      lipid bilayer whereas the polar regions face the aqueous environment. Analyses of
      membrane proteins in nanodiscs have significant advantages over liposome because
      the particles are small, homogeneous and water-soluble. In addition, biochemical
      and biophysical methods normally reserved to soluble proteins can be applied, and
      from either side of the membrane. In this visual protocol, we present a step-by
      step reconstitution of a well characterized bacterial ABC transporter, the MalE
      MalFGK2 complex. The formation of the disc is a self-assembly process that
      depends on hydrophobic interactions taking place during the progressive removal
      of the detergent. We describe the essential steps and we highlight the importance
      of choosing a correct protein-to-lipid ratio in order to limit the formation of
      aggregates and larger polydisperse liposome-like particles. Simple quality
      controls such as gel filtration chromatography, native gel electrophoresis and
      dynamic light scattering spectroscopy ensure that the discs have been properly
      reconstituted.

PMID- 22951951
TI  - Why are patients with chronic myeloid leukaemia (non-)adherent?

PMID- 22951952
TI  - Nod2 deficiency impairs inflammatory and epithelial aspects of the cutaneous
      wound-healing response.
AB  - Infection is a significant causative factor in human chronic wounds that fail to
      heal. Complex innate host response mechanisms have evolved whereby potentially
      harmful pathogens are recognized by multiple host pattern recognition receptors
      (PRRs), yet understanding of PRR function, or dysfunction, in the context of
      chronic wounds remains limited. NOD2, a cytoplasmic PRR, has been strongly
      implicated in chronic inflammation of the gut, where loss-of-function mutations
      have been linked to Crohn's disease; however, cutaneous Nod2 function remains
      poorly characterized. Here we demonstrate an important role for Nod2 in murine
      skin wound healing. Cutaneous Nod2 is induced in key wound cell types in response
      to injury. In the absence of Nod2, mice display a substantial delay in acute
      wound repair associated with epithelial and inflammatory changes. Specifically,
      Nod2-null mice display altered epidermal migration and proliferation, an initial
      delay in neutrophil recruitment associated with decreased expression of the
      chemokine receptor CXCR2, and reduced numbers of alternatively activated
      macrophages (Ym1(+)  cells). Somewhat surprisingly, these Nod2-null phenotypes
      were associated with little or no expression change in other PRRs, even though
      compensatory mechanisms have been shown to exist. In this study we show that
      healing in TLR2-null mice was essentially normal. These findings reveal a novel
      intrinsic role for Nod2 in cutaneous wound repair in addition to its role in
      recognizing invading pathogens.

PMID- 22951953
TI  - Portable automatic bioaerosol sampling system for rapid on-site detection of
      targeted airborne microorganisms.
AB  - Bioaerosols could cause various severe human and animal diseases and their
      opportune and qualitative precise detection and control is becoming a significant
      scientific and technological topic for consideration. Over the last few decades
      bioaerosol detection has become an important bio-defense related issue. Many
      types of portable and stationary bioaerosol samplers have been developed and, in
      some cases, integrated into automated detection systems utilizing various
      microbiological techniques for analysis of collected microbes. This paper
      describes a personal sampler used in conjunction with a portable real-time PCR
      technique. It was found that a single fluorescent dye could be successfully used
      in multiplex format for qualitative detection of numerous targeted bioaerosols in
      one PCR tube making the suggested technology a reliable "first alert" device.
      This approach has been specifically developed and successfully verified for rapid
      detection of targeted microorganisms by portable PCR devices, which is especially
      important under field conditions, where the number of microorganisms of interest
      usually exceeds the number of available PCR reaction tubes. The approach allows
      detecting targeted microorganisms and triggering some corresponding sanitary and
      quarantine procedures to localize possible spread of dangerous infections.
      Following detailed analysis of the sample under controlled laboratory conditions
      could be used to exactly identify which particular microorganism out of a
      targeted group has been rapidly detected in the field. It was also found that the
      personal sampler has a collection efficiency higher than 90% even for small-sized
      viruses (>20 nm) and stable performance over extended operating periods. In
      addition, it was found that for microorganisms used in this project
      (bacteriophages MS2 and T4) elimination of nucleic acids isolation and
      purification steps during sample preparation does not lead to the system
      sensitivity reduction, which is extremely important for development of miniature
      bioaerosol monitoring instrumentation in the future.

PMID- 22951954
TI  - Fast-track practice in cardiac surgery: results and predictors of outcome.
AB  - OBJECTIVES: Various studies have shown different parameters as independent risk
      factors in predicting the success of fast-track postoperative management in
      cardiac surgery. In the present study, we evaluated our 7-year experience with
      the fast-track protocol and investigated the preoperative predictors of
      successful outcome. METHODS: Between 2004 and 2010, 5367 consecutive patients
      undergoing cardiac surgery were preoperatively selected for postoperative
      admission in the postanaesthesia care unit (PACU) and were included in this
      study. These patients were then transferred to the ordinary ward on the same day
      of the operation. The primary end-point of the study was the success of the PACU
      protocol, defined as discharge to the ward on the same day, no further admission
      to the intensive care unit and no operative mortality. Logistic regression
      analysis was performed to detect the independent risk factors for failure of the
      PACU pathway. RESULTS: Of 11,895 patients undergoing cardiac surgery, 5367
      (45.2%) were postoperatively admitted to the PACU. The protocol was successful in
      4510 patients (84.0%). Using the multivariate logistic regression analysis, older
      age and left ventricular dysfunction were found to be independent risk factors
      for failure of the PACU protocol [odds ratio of 0.98/year (0.97-0.98) and 0.31
      (0.14-0.70), respectively]. CONCLUSIONS: Our fast-track management, called the
      PACU protocol, is efficient and safe for the postoperative management of selected
      patients undergoing cardiac surgery. Age and left ventricular dysfunction are
      significant preoperative predictors of failure of this protocol.

PMID- 22951956
TI  - New method to assess manual lymph drainage using lymphoscintigraphy.
AB  - The aim of this study was to describe a new variation of the technique to
      evaluate lymph drainage utilizing lymphoscintigraphy. A LS scan marks the route
      of lymphatic vessels and may be used to assess both manual lymph drainage and
      lymph drainage after using some apparatuses. This evaluation may be dynamic,
      collecting images whilst performing lymph drainage or static, with scans before
      and after the lymph drainage procedure.

PMID- 22951957
TI  - Synthesis, optical properties, and electronic structures of fully core-modified
      porphyrin dications and isophlorins.
AB  - The synthesis, structures, optical properties, and electronic structures of the
      tetraphenyltetrathiaporphyrin dication (S(4)TPP(2+), 6) and
      tetrakis(pentafluorophenyl)tetrathiaisophlorin (S(4)F(20)TPP, 7) are reported.
      S(4)TPP(2+) (6) and S(4)F(20)TPP (7) were synthesized by acid-catalyzed
      condensation of the corresponding hydroxylmethylthiophene, followed by oxidation.
      The electronic structures of S(4)TPP(2+) (6) and S(4)F(20)TPP (7) were analyzed
      by using UV/Vis-absorption spectroscopy and by magnetic circular dichroism (MCD)
      spectroscopy and the bands were assigned by using time-dependent density
      functional theory (TD-DFT) and ZINDO/s calculations. A red-shift of the Q bands
      of S(4)TPP(2+) (6) is observed relative to the spectra of tetraphenylporphyrins
      because a destabilization of the HOMO leads to a narrower HOMO-LUMO band-gap.
      Michl's perimeter model was used to assign the absorption bands and MCD spectra
      of S(4)F(20)TPP (7). Current-density maps and nucleus-independent chemical-shift
      (NICS) calculations of S(4)TPP(2+) (6) and of a model compound predict marked
      modification to the diamagnetic ring current, whilst nonaromatic character is
      predicted for S(4)F(20)TPP (7).

PMID- 22951958
TI  - An efficient and cost-effective protocol for selecting transcription factor
      binding sites that reduces isotope usage.
AB  - To function, transcription factors must position themselves by binding to DNA in
      a sequence-specific manner. Knowing the binding sites of these factors is a
      necessary step in understanding their activity. The standard protocols used for
      selecting a consensus-binding sequence for a DNA binding domain often require the
      use of radioisotopes to attain the necessary level of power in the assay.
      Alternatives are often less sensitive and may require an expensive apparatus for
      visualizing. We have created a modified binding site selection (BSS) protocol to
      improve efficiency and decrease the use of radioisotope. A GST affinity-tagged
      DNA binding domain construct was immobilized on a GSH affinity column and used to
      select from a randomized oligonucleotide library identical to those typically
      used in a radiolabeled BSS protocol. This produced a library specifically pre
      enriched for use in a standard sequential EMSA selection. Use of a pre-enriched
      library reduced the total number of labeled rounds required for selection,
      decreasing the use of radioisotope while maintaining efficacy. The protocol was
      used to select for the binding sequence for several Drosophila melanogaster
      transcription factors. The consensus sequence was then shown by competitive
      binding experiments to associate with the protein in a sequence-dependent manner.

PMID- 22951959
TI  - Gene silencing of MK2 in hard-to-transfect human U937 cells.
AB  - Genetic modifications used to answer biological questions in cultured cells are
      widely used in basic research. Common transfection methods are based on viral
      components causing cell activation or chemical modifications of small interfering
      RNA and cytotoxic reagents. Here, we report a rapid and efficient approach to
      transfect hard-to-transfect human U937 cells via the HVJ Envelope vector system,
      independent from special transfection media or immobilization of cells. This
      protocol provides a convenient means of knocking down MAPK-activated kinase 2 in
      hard-to-transfect cells to study inflammation, cell adhesion, and migration
      characteristics.

PMID- 22951960
TI  - Phosphopeptide characterization by mass spectrometry using reversed-phase
      supports for solid-phase beta-elimination/Michael addition.
AB  - We have adapted the Ba(2+) ion-catalyzed concurrent Michael addition reaction to
      solid-phase derivatization on ZipTip(C18) pipette tips using 2-aminoethanethiol
      as a nucleophile. This approach provides several advantages over the classical in
      solution-based techniques, including ease of operation, completeness of reaction,
      improved throughput, efficient use of dilute samples, and amenability to
      automation. Phosphoseryl and phosphothreonyl peptides, as well as phosphoserine
      peptides with adjoining prolines, were used to optimize the reaction conditions,
      which proved highly compatible with the integrity of the samples. The analyte was
      recovered from the silica-based C18 resin at minimal sample loss. The use of the
      protocol for improved phosphopeptide detection by signal enhancement was
      demonstrated with low-level amounts of proteolytic digests from model proteins
      and experimental samples, an effect found especially prominent with multiple
      phosphorylated species. The reaction products proved highly suitable for
      structural characterization by collisionally induced dissociation (CID), and the
      resultant increased spectral information content, greatly facilitating mapping of
      the site of phosphorylation. In select cases, the method enables phosphorylation
      site localization within known protein sequences on the basis of single-stage
      data alone. The solid-phase strategy presented here provides a simple, versatile,
      and efficient tool for phosphopeptide structural characterization equipment
      readily available in most biological laboratories.

PMID- 22951961
TI  - Development of the "Three-step MACS": a novel strategy for isolating rare cell
      populations in the absence of known cell surface markers from complex animal
      tissue.
AB  - To circumvent the difficulty of isolating specific cell populations by MACS from
      dissociated complex animal tissue, when their proportions reached levels similar
      to that of the background, we developed the "Three-step MACS" strategy. Cells of
      interest are defined by their expression of a particular gene(s) of interest
      rather by than their natural cell surface markers or size. A two-component
      transgenic cell surface protein, for two sequential rounds of MACS, is expressed
      under the promoter control of the endogenous gene of interest by means of gene
      targeting and the generation of transgenic tissue. An initial step to remove dead
      cells is also used. Here, we describe proof-of-concept experiments, using the
      biotin acceptor peptide (BAP)-low-affinity nerve growth factor receptor as the
      two-component protein. The first component, the BAP, can be biotinylated in
      specific subsets of cells expressing a particular gene by expressing the
      biotinylating enzyme, hBirA = humanized BirA (hBirA), under the promoter control
      of another gene defining the specific subpopulation. We showed that a rare
      population of cells (1.1% of the 13.5 days postcoital mouse embryo) could be
      enriched to a sufficiently high purity (84.4%). From another sample with 0.1% of
      our cells of interest, we achieved a 40.3% pure sample. The low cost, speed, and
      technical ease of the Three-step MACS also make it scalable and hence, an ideal
      method for preparing sufficient quantities of biological samples for sensitive,
      high-throughput assays.

PMID- 22951962
TI  - Ol4E-T, a eukaryotic translation initiation factor 4E-binding protein of medaka
      fish (Oryzias latipes), can interact with nanos3 and vasa in vitro.
AB  - Maternal factors have essential roles in the specification and development of
      germ cells in metazoans. In Drosophila, a number of genes such as oskar, vasa,
      nanos, and tudor are required for specific steps in pole cell formation and
      further germline development. Drosophila cup, another maternal factor, is
      confirmed as a main factor in normal oogenesis, maintenance, and survival of
      female germ-line stem cells by interaction with Nanos. Through searching for the
      homolog of Drosophila cup in the medaka, the homolog of eukaryotic translation
      initiation factor 4E (eIF4E)-transporter, named Ol4E-T, was identified. Reverse
      transcription-polymerase chain reaction (RT-PCR) and in situ hybridization
      revealed that Ol4E-T is maternally deposited in the embryo and Ol4E-T expression
      is maintained throughout embryogenesis. Ol4E-T is predominantly expressed in the
      adult gonads. In the testes, Ol4E-T is expressed in the same regions where medaka
      vasa, named olvas is expressed. In the ovary, expression of Ol4E-T conforms to
      that of nanos3 and olvas. Ol4E-T harbors a well-conserved eIF4E-binding motif,
      YTKEELL, by which Ol4E-T interacts with eIF4E in medaka. Additionally, Ol4E-T can
      interact with medaka Nanos3 and Olvas, as shown by yeast two hybridization. The
      spatial expression and interactions between Ol4E-T with germ cell markers Olvas
      and Nanos3 suggest a role for Ol4E-T in germ-line development in medaka.

PMID- 22951963
TI  - Outcomes following pharyngolaryngectomy with fasciocutaneous free flap
      reconstruction and salivary bypass tube.
AB  - OBJECTIVES/HYPOTHESIS: Reconstruction of the pharyngoesophageal defects is one of
      the most challenging for head and neck surgeons. We evaluated our experience in
      the hypopharyngeal reconstruction using a fasciocutaneous free flap in
      conjunction with a Montgomery salivary bypass tube (MSBT). STUDY DESIGN:
      Retrospective review. METHODS: The charts of 55 patients who had undergone
      hypopharynx reconstruction using either a radial forearm free flap (RFFF) (24) or
      an anterolateral thigh (ALT) flap (31) with MSBT were reviewed. There were 40
      circumferential and 15 near-circumferential defects. Outcomes analyzed included
      fistula and stricture rates and swallowing function. RESULTS: Pharyngocutaneous
      fistula occurred in 9% of patients (16% using RFFF and 3% using ALT), and
      strictures occurred in 5% (8% using RFFF and 3% using ALT). Of patients
      reconstructed with this technique, 95% were able to resume oral alimentation.
      CONCLUSIONS: The use of fasciocutaneous free flaps in conjunction with the MSBT
      is a useful tool for pharyngoesophageal reconstruction.

PMID- 22951964
TI  - NHS has relied too heavily on regulation to improve quality of care, conference
      is told.

PMID- 22951965
TI  - European court overturns preimplantation testing ban.

PMID- 22951966
TI  - Observations of increased tropical rainfall preceded by air passage over forests.
AB  - Vegetation affects precipitation patterns by mediating moisture, energy and trace
      gas fluxes between the surface and atmosphere. When forests are replaced by
      pasture or crops, evapotranspiration of moisture from soil and vegetation is
      often diminished, leading to reduced atmospheric humidity and potentially
      suppressing precipitation. Climate models predict that large-scale tropical
      deforestation causes reduced regional precipitation, although the magnitude of
      the effect is model and resolution dependent. In contrast, observational studies
      have linked deforestation to increased precipitation locally but have been unable
      to explore the impact of large-scale deforestation. Here we use satellite remote
      sensing data of tropical precipitation and vegetation, combined with simulated
      atmospheric transport patterns, to assess the pan-tropical effect of forests on
      tropical rainfall. We find that for more than 60 per cent of the tropical land
      surface (latitudes 30 degrees south to 30 degrees north), air that has passed
      over extensive vegetation in the preceding few days produces at least twice as
      much rain as air that has passed over little vegetation. We demonstrate that this
      empirical correlation is consistent with evapotranspiration maintaining
      atmospheric moisture in air that passes over extensive vegetation. We combine
      these empirical relationships with current trends of Amazonian deforestation to
      estimate reductions of 12 and 21 per cent in wet-season and dry-season
      precipitation respectively across the Amazon basin by 2050, due to less-efficient
      moisture recycling. Our observation-based results complement similar estimates
      from climate models, in which the physical mechanisms and feedbacks at work could
      be explored in more detail.

PMID- 22951967
TI  - Quantum teleportation over 143 kilometres using active feed-forward.
AB  - The quantum internet is predicted to be the next-generation information
      processing platform, promising secure communication and an exponential speed-up
      in distributed computation. The distribution of single qubits over large
      distances via quantum teleportation is a key ingredient for realizing such a
      global platform. By using quantum teleportation, unknown quantum states can be
      transferred over arbitrary distances to a party whose location is unknown. Since
      the first experimental demonstrations of quantum teleportation of independent
      external qubits, an internal qubit and squeezed states, researchers have
      progressively extended the communication distance. Usually this occurs without
      active feed-forward of the classical Bell-state measurement result, which is an
      essential ingredient in future applications such as communication between quantum
      computers. The benchmark for a global quantum internet is quantum teleportation
      of independent qubits over a free-space link whose attenuation corresponds to the
      path between a satellite and a ground station. Here we report such an experiment,
      using active feed-forward in real time. The experiment uses two free-space
      optical links, quantum and classical, over 143 kilometres between the two Canary
      Islands of La Palma and Tenerife. To achieve this, we combine advanced techniques
      involving a frequency-uncorrelated polarization-entangled photon pair source,
      ultra-low-noise single-photon detectors and entanglement-assisted clock
      synchronization. The average teleported state fidelity is well beyond the
      classical limit of two-thirds. Furthermore, we confirm the quality of the quantum
      teleportation procedure without feed-forward by complete quantum process
      tomography. Our experiment verifies the maturity and applicability of such
      technologies in real-world scenarios, in particular for future satellite-based
      quantum teleportation.

PMID- 22951968
TI  - A transcriptomic hourglass in plant embryogenesis.
AB  - Animal and plant development starts with a constituting phase called
      embryogenesis, which evolved independently in both lineages. Comparative anatomy
      of vertebrate development--based on the Meckel-Serres law and von Baer's laws of
      embryology from the early nineteenth century--shows that embryos from various
      taxa appear different in early stages, converge to a similar form during mid
      embryogenesis, and again diverge in later stages. This morphogenetic series is
      known as the embryonic 'hourglass', and its bottleneck of high conservation in
      mid-embryogenesis is referred to as the phylotypic stage. Recent analyses in
      zebrafish and Drosophila embryos provided convincing molecular support for the
      hourglass model, because during the phylotypic stage the transcriptome was
      dominated by ancient genes and global gene expression profiles were reported to
      be most conserved. Although extensively explored in animals, an embryonic
      hourglass has not been reported in plants, which represent the second major
      kingdom in the tree of life that evolved embryogenesis. Here we provide
      phylotranscriptomic evidence for a molecular embryonic hourglass in Arabidopsis
      thaliana, using two complementary approaches. This is particularly significant
      because the possible absence of an hourglass based on morphological features in
      plants suggests that morphological and molecular patterns might be uncoupled.
      Together with the reported developmental hourglass patterns in animals, these
      findings indicate convergent evolution of the molecular hourglass and a conserved
      logic of embryogenesis across kingdoms.

PMID- 22951969
TI  - Environmental science: The rainforest's water pump.

PMID- 22951970
TI  - Ploughing the deep sea floor.
AB  - Bottom trawling is a non-selective commercial fishing technique whereby heavy
      nets and gear are pulled along the sea floor. The direct impact of this technique
      on fish populations and benthic communities has received much attention, but
      trawling can also modify the physical properties of seafloor sediments, water
      sediment chemical exchanges and sediment fluxes. Most of the studies addressing
      the physical disturbances of trawl gear on the seabed have been undertaken in
      coastal and shelf environments, however, where the capacity of trawling to modify
      the seafloor morphology coexists with high-energy natural processes driving
      sediment erosion, transport and deposition. Here we show that on upper
      continental slopes, the reworking of the deep sea floor by trawling gradually
      modifies the shape of the submarine landscape over large spatial scales. We found
      that trawling-induced sediment displacement and removal from fishing grounds
      causes the morphology of the deep sea floor to become smoother over time,
      reducing its original complexity as shown by high-resolution seafloor relief
      maps. Our results suggest that in recent decades, following the industrialization
      of fishing fleets, bottom trawling has become an important driver of deep
      seascape evolution. Given the global dimension of this type of fishery, we
      anticipate that the morphology of the upper continental slope in many parts of
      the world's oceans could be altered by intensive bottom trawling, producing
      comparable effects on the deep sea floor to those generated by agricultural
      ploughing on land.

PMID- 22951971
TI  - Graphene and graphene oxide can "lubricate" ionic liquids based on specific
      surface interactions leading to improved low-temperature hypergolic performance.
AB  - Space-qualified lubricants: Graphene and graphene oxide (r-GO) can strongly
      improve the low-temperature performance of hypergolic ionic liquids by reduction
      of viscosity. Key to success is to match the graphene type to the specific ionic
      liquid functionality.

PMID- 22951972
TI  - Determining soil-transmitted helminth infection status and physical fitness of
      school-aged children.
AB  - Soil-transmitted helminth (STH) infections are common. Indeed, more than 1
      billion people are affected, mainly in the developing world where poverty
      prevails and hygiene behavior, water supply, and sanitation are often deficient.
      Ascaris lumbricoides, Trichuris trichiura, and the two hookworm species,
      Ancylostoma duodenale and Necator americanus, are the most prevalent STHs. The
      estimated global burden due to hookworm disease, ascariasis, and trichuriasis is
      22.1, 10.5, and 6.4 million disability-adjusted life years (DALYs), respectively.
      Furthermore, an estimated 30-100 million people are infected with Strongyloides
      stercoralis, the most neglected STH species of global significance which arguably
      also causes a considerable public health impact. Multiple-species infections
      (i.e., different STHs harbored in a single individual) are common, and infections
      have been linked to lowered productivity and thus economic outlook of developing
      countries. For the diagnosis of common STHs, the World Health Organization (WHO)
      recommends the Kato-Katz technique, which is a relatively straightforward method
      for determining the prevalence and intensity of such infections. It facilitates
      the detection of parasite eggs that infected subjects pass in their feces. With
      regard to the diagnosis of S. stercoralis, there is currently no simple and
      accurate tool available. The Baermann technique is the most widely employed
      method for its diagnosis. The principle behind the Baermann technique is that
      active S. stercoralis larvae migrate out of an illuminated fresh fecal sample as
      the larvae are phototactic. It requires less sophisticated laboratory materials
      and is less time consuming than culture and immunological methods. Morbidities
      associated with STH infections range from acute but common symptoms, such as
      abdominal pain, diarrhea, and pruritus, to chronic symptoms, such as anemia,
      under- and malnutrition, and cognitive impairment. Since the symptoms are
      generally unspecific and subtle, they often go unnoticed, are considered a normal
      condition by affected individuals, or are treated as symptoms of other diseases
      that might be more common in a given setting. Hence, it is conceivable that the
      true burden of STH infections is underestimated by assessment tools relying on
      self-declared signs and symptoms as is usually the case in population-based
      surveys. In the late 1980s and early 1990s, Stephenson and colleagues highlighted
      the possibility of STH infections lowering the physical fitness of boys aged 6-12
      years. This line of scientific inquiry gained new momentum recently. The 20-meter
      (m) shuttle run test was developed and validated by Leger et al. and is used
      worldwide to measure the aerobic fitness of children. The test is easy to
      standardize and can be performed wherever a 20-m long and flat running course and
      an audio source are available, making its use attractive in resource-constrained
      settings. To facilitate and standardize attempts at assessing whether STH
      infections have an effect on the physical fitness of school-aged children, we
      present methodologies that diagnose STH infections or measure physical fitness
      that are simple to execute and yet, provide accurate and reproducible outcomes.
      This will help to generate new evidence regarding the health impact of STH
      infections.

PMID- 22951973
TI  - Stereoselective total synthesis of dinemasone A by double intramolecular hetero
      Michael addition (DIHMA).
AB  - The first total synthesis of dinemasone A, a bioactive metabolite with a
      spiroketal moiety, is described. The main strategy for the construction of the
      spiroketal unit involves a double intramolecular hetero-Michael addition (DIHMA)
      of an ynone moiety. The thus obtained axial-equatorial mono anomeric spiroketal,
      on spiroepimerization with ZnBr(2), was converted into the requisite axial-axial
      double anomeric spiroketal. The ynone moiety with four stereocentres, was
      prepared from a chiral propargylic alcohol (C5-C11 fragment) and a dihydroxy
      aldehyde (C1-C4 fragment), which in turn were obtained from D-mannitol and crotyl
      alcohol respectively.

PMID- 22951974
TI  - Comments on "assessment of prenatal mercury exposure in a predominantly Caribbean
      immigrant community in Brooklyn, NY".

PMID- 22951975
TI  - Oncogene-dependent control of miRNA biogenesis and metastatic progression in a
      model of undifferentiated pleomorphic sarcoma.
AB  - Undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue
      malignancies. Patients with large, high-grade sarcomas often develop fatal lung
      metastases. Understanding the mechanisms underlying sarcoma metastasis is needed
      to improve treatment of these patients. Micro-RNAs (miRNAs) are a class of small
      RNAs that post-transcriptionally regulate gene expression. Global alterations in
      miRNAs are frequently observed in a number of disease states including cancer.
      The signalling pathways that regulate miRNA biogenesis are beginning to emerge.
      To test the relevance of specific oncogenic mutations in miRNA biogenesis in
      sarcoma, we used primary soft tissue sarcomas expressing either Braf(V600E) or
      Kras(G12D). We found that Braf(V600E) mutant tumours, which have increased MAPK
      signalling, have higher levels of mature miRNAs and enhanced miRNA processing. To
      investigate the relevance of oncogene-dependent alterations in miRNA biogenesis,
      we introduced conditional mutations in Dicer and showed that Dicer
      haploinsufficiency promotes the development of distant metastases in an oncogene
      dependent manner. These results demonstrate that a specific oncogenic mutation
      can cooperate with mutation in Dicer to promote tumour progression in vivo.

PMID- 22951978
TI  - Exocyclic bond cleavage in oxaphosphirane complexes?
AB  - A first computational insight into the intrinsic strength of exocyclic bonds to
      phosphorus in oxaphosphirane kappaP-pentacarbonylmetal(0) complexes 1a-f (M=Cr,
      Mo) is provided using a set of P-R derivatives (R=Me, tBu, CPh(3)). Whereas
      homolytic cleavage of the exocyclic P-R bond was found to be always unfavored
      (for neutral complexes), heterolytic cleavage leading to a carbocation R(+)
      moiety and the oxaphosphiranide complex 2(-) constitutes the lowest-energy
      process, especially if R is bulky and can stabilize the positive charge, that is,
      triphenylmethyl (trityl), efficiently. The energies required for P-M bond
      cleavage are about 30 kcal mol(-1), and decrease with the increasing bulk of the
      R substituent (from Me to trityl) and ongoing from Cr to Mo. The reactivities of
      complexes 1a-f towards oxidative and reductive single electron transfer (SET)
      reactions were analyzed using the facile variation of bond-strength-related
      descriptors (VBSD) methodology, thus enabling the design of synthetically useful
      strategies addressing decomplexation and P-functionalization. Reductive SET
      reactions with sodium naphthalenides enable selective P-M bond cleavage (i.e.,
      decomplexation) for the case of P-Me and P-tBu substitution, whereas reductive P
      R bond cleavage is favored in the case of the P-trityl complexes 1c,f, and
      results in the formation of the (anionic) oxaphosphiranide complex 2(-), which
      may be regarded as a potential key intermediate for further P-functionalization.

PMID- 22951977
TI  - Glutathiyl radical as an intermediate in glutathione nitrosation.
AB  - Nitrosation of thiols is thought to be mediated by dinitrogen trioxide (N(2)O(3))
      or by nitrogen dioxide radical (()NO(2)). A kinetic study of glutathione (GSH)
      nitrosation by NO donors in aerated buffered solutions was undertaken. S
      nitrosoglutathione (GSNO) formation was assessed spectrophotometrically and by
      chemiluminescence. The results suggest an increase in the rate of GSNO formation
      with an increase in GSH with a half-maximum constant EC(50) that depends on NO
      concentration. Our observed increase in EC(50) with NO concentration suggests a
      significant contribution of ()NO(2)-mediated nitrosation with the glutathiyl
      radical as an intermediate in the production of GSNO.

PMID- 22951979
TI  - Theria-specific homeodomain and cis-regulatory element evolution of the Dlx3-4
      bigene cluster in 12 different mammalian species.
AB  - The mammalian Dlx3 and Dlx4 genes are configured as a bigene cluster, and their
      respective expression patterns are controlled temporally and spatially by cis
      elements that largely reside within the intergenic region of the cluster.
      Previous work revealed that there are conspicuously conserved elements within the
      intergenic region of the Dlx3-4 bigene clusters of mouse and human. In this paper
      we have extended these analyses to include 12 additional mammalian taxa
      (including a marsupial and a monotreme) in order to better define the nature and
      molecular evolutionary trends of the coding and non-coding functional elements
      among morphologically divergent mammals. Dlx3-4 regions were fully sequenced from
      12 divergent taxa of interest. We identified three theria-specific amino acid
      replacements in homeodomain of Dlx4 gene that functions in placenta. Sequence
      analyses of constrained nucleotide sites in the intergenic non-coding region
      showed that many of the intergenic conserved elements are highly conserved and
      have evolved slowly within the mammals. In contrast, a branchial
      arch/craniofacial enhancer I37-2 exhibited accelerated evolution at the branch
      between the monotreme and therian common ancestor despite being highly conserved
      among therian species. Functional analysis of I37-2 in transgenic mice has shown
      that the equivalent region of the platypus fails to drive transcriptional
      activity in branchial arches. These observations, taken together with our
      molecular evolutionary data, suggest that theria-specific episodic changes in the
      I37-2 element may have contributed to craniofacial innovation at the base of the
      mammalian lineage.

PMID- 22951980
TI  - Effect of grapefruit juice on bioavailability of montelukast.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate possible
      interactions between grapefruit juice and montelukast for up to 4 hours. STUDY
      DESIGN: A prospective, crossover study with 23 healthy volunteers was performed
      in two sessions. METHODS: In the first session, volunteers were treated with oral
      montelukast 10 mg once daily with 250 ml water. After a 10-day washout period,
      the same volunteers were treated with 10 mg montelukast with 250 ml grapefruit
      juice. Blood samples were collected 2, 3, and 4 hours after drug administration
      and kept at -80 degrees C after both applications. Plasma samples were analyzed
      for montelukast concentration. RESULTS: The mean plasma concentration of
      montelukast across all time intervals was significantly greater (P = 0.0001) for
      those given grapefruit juice (517, 484, and 440) versus those treated with water
      (366, 356, and 292). Moreover, with respect to the time the sample was collected,
      there was no significant difference (P = 0.13) in the mean total plasma
      concentration up to 4 hours after montelukast ingestion for either group. There
      was a significant difference between the groups according to the area under curve
      with regard to marginal and cumulative values for all different time intervals (P
      < 0.05). CONCLUSIONS: Plasma concentration of montelukast was higher when
      administered with grapefruit juice, as compared to with water. This may have been
      due to the effect of grapefruit on liver metabolism of montelukast and the
      cytochrome P450 system.

PMID- 22951981
TI  - Spontaneous formation of IpaB ion channels in host cell membranes reveals how
      Shigella induces pyroptosis in macrophages.
AB  - The Gram-negative bacterium Shigella flexneri invades the colonic epithelium and
      causes bacillary dysentery. S. flexneri requires the virulence factor invasion
      plasmid antigen B (IpaB) to invade host cells, escape from the phagosome and
      induce macrophage cell death. The mechanism by which IpaB functions remains
      unclear. Here, we show that purified IpaB spontaneously oligomerizes and inserts
      into the plasma membrane of target cells forming cation selective ion channels.
      After internalization, IpaB channels permit potassium influx within endolysosomal
      compartments inducing vacuolar destabilization. Endolysosomal leakage is followed
      by an ICE protease-activating factor-dependent activation of Caspase-1 in
      macrophages and cell death. Our results provide a mechanism for how the effector
      protein IpaB with its ion channel activity causes phagosomal destabilization and
      induces macrophage death. These data may explain how S. flexneri uses secreted
      IpaB to escape phagosome and kill the host cells during infection and, may be
      extended to homologs from other medically important enteropathogenic bacteria.

PMID- 22951982
TI  - Leishmania mexicana metacaspase is a negative regulator of amastigote
      proliferation in mammalian cells.
AB  - Metacaspases (MCAs) are caspase family cysteine peptidases that have been
      implicated in cell death processes in plants, fungi and protozoa. MCAs have also
      been suggested to be involved in cell cycle control, differentiation and
      clearance of aggregates; they are virulence factors. Dissecting the function of
      MCAs has been complicated by the presence in many organisms of multiple MCA genes
      or limitations on genetic manipulation. We describe here the creation of a MCA
      gene-deletion mutant (Deltamca) in the protozoan parasite Leishmania mexicana,
      which has allowed us to dissect the role of the parasite's single MCA gene in
      cell growth and cell death. Deltamca parasites are viable as promastigotes, and
      differentiate normally to the amastigote form both in in vitro macrophages
      infection and in mice. Deltamca promastigotes respond to cell death inducers such
      as the drug miltefosine and H(2)O(2) similarly to wild-type (WT) promastigotes,
      suggesting that MCAs do not have a caspase-like role in execution of L. mexicana
      cell death. Deltamca amastigotes replicated significantly faster than WT
      amastigotes in macrophages and in mice, but not as axenic culture in vitro. We
      propose that the Leishmania MCA acts as a negative regulator of amastigote
      proliferation, thereby acting to balance cell growth and cell death.

PMID- 22951984
TI  - Induction of autophagy does not alter the anti-tumor effects of HDAC inhibitors.

PMID- 22951983
TI  - Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the
      HIF1-REDD1-TSC1-mTORC1-DEPTOR axis.
AB  - MLN4924, a newly discovered small molecule inhibitor of NEDD8-activating enzyme
      (NAE), inactivates Cullin-RING E3 ubiquitin Ligases (CRLs) by blocking cullin
      neddylation. As a result, MLN4924 causes accumulation of several key substrates
      of CRLs and effectively suppresses tumor cell growth by inducing apoptosis and
      senescence. However, the role of MLN4924 in induction of autophagy and its
      biological significance are totally unknown. Here we showed that MLN4924
      effectively induces autophagy in both time- and dose-dependent manners in
      multiple human cancer lines, indicating a general phenomenon. Mechanistically, by
      inactivating CRLs, MLN4924 causes accumulation of DEPTOR and HIF1alpha. The siRNA
      knockdown and gene KO studies showed that DEPTOR and the HIF1-REDD1-TSC1 axis are
      responsible for MLN4924-induced autophagy via inhibiting mTORC1. Biologically,
      autophagy is a survival signal to tumor cells, and blockage of autophagy via
      siRNA knockdown, gene KO and small molecule inhibitor remarkably enhanced MLN4924
      induced apoptosis. Our study reveals an uncharacterized mechanism of MLN4924
      action and provides the proof-of-concept evidence for strategic drug combination
      of MLN4924 with an autophagy inhibitor for maximal killing of tumor cells via
      enhancing apoptosis.

PMID- 22951985
TI  - Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for
      CD95L- and TRAIL-induced apoptosis.
AB  - In this study, we have analysed the apoptotic effects of the ubiquitous
      environmental toxin benzo[a]pyrene (BP) in HaCaT cells and human keratinocytes.
      Although prolonged exposure to BP was not cytotoxic on its own, a strong
      enhancement of CD95 (Fas)-mediated apoptosis was observed with BP at
      concentrations activating the aryl hydrocarbon receptor (AhR). Importantly, the
      ultimately mutagenic BP-metabolite, that is, (+)-anti-BP-7,8-diol-9,10-epoxide
      (BPDE), failed to enhance CD95-mediated cell death, suggesting that the observed
      pro-apoptotic effect of BP is neither associated with DNA adducts nor DNA-damage
      related signalling. CD95-induced apoptosis was also enhanced by beta
      naphtoflavone, a well-known agonist of the AhR that does not induce DNA damage,
      thus suggesting a crucial role for AhR activation. Consistently, BP failed to
      sensitise for CD95L-induced apoptosis in AhR knockdown HaCaT cells. Furthermore,
      inhibition of CYP1A1 and/or 1B1 expression did not affect the pro-apoptotic
      crosstalk. Exposure to BP did not increase expression of CD95, but led to
      augmented activation of caspase-8. Enhancement of apoptosis was also observed
      with the TRAIL death receptors that activate caspase-8 and apoptosis by similar
      mechanisms as CD95. Together, these observations indicate an interference of AhR
      signalling with the activity of receptor-associated signalling intermediates that
      are shared by CD95 and TRAIL receptors. Our data thus suggest that AhR agonists
      can enhance cytokine-mediated adversity upon dermal exposure.

PMID- 22951986
TI  - Low molecular weight, non-peptidic agonists of TrkA receptor with NGF-mimetic
      activity.
AB  - Exploitation of the biologic activity of neurotrophins is desirable for medical
      purposes, but their protein nature intrinsically bears adverse pharmacokinetic
      properties. Here, we report synthesis and biologic characterization of a novel
      class of low molecular weight, non-peptidic compounds with NGF (nerve growth
      factor)-mimetic properties. MT2, a representative compound, bound to Trk
      (tropomyosin kinase receptor)A chain on NGF-sensitive cells, as well as in cell
      free assays, at nanomolar concentrations and induced TrkA autophosphorylation and
      receptor-mediated internalization. MT2 binding involved at least two amino-acid
      residues within TrkA molecule. Like NGF, MT2 increased phosphorylation of
      extracellular signal-regulated kinase 1/2 and Akt proteins and production of MKP
      1 phosphatase (dual specificity phosphatase 1), modulated p38 mitogen-activated
      protein kinase activation,sustained survival of serum-starved PC12 or RDG cells,
      and promoted their differentiation. However, the intensity of such responses was
      heterogenous, as the ability of maintaining survival was equally possessed by NGF
      and MT2, whereas the induction of differentiation was expressed at definitely
      lower levels by the mimetic. Analysis of TrkA autophosphorylation patterns
      induced by MT2 revealed a strong tyrosine (Tyr)490 and a limited Tyr785 and
      Tyr674/675 activation, findings coherent with the observed functional
      divarication. Consistently, in an NGF-deprived rat hippocampal neuronal model of
      Alzheimer Disease, MT2 could correct the biochemical abnormalities and sustain
      cell survival. Thus, NGF mimetics may reveal interesting investigational tools in
      neurobiology, as well as promising drug candidates.

PMID- 22951987
TI  - InCl3-catalyzed synthesis of 1,2-dimetallic compounds by direct insertion of
      aluminum or zinc powder.
AB  - In-sertion of metal: Catalytic amounts of InCl(3)  allow the insertion of
      aluminum and zinc into aromatic 1,2-dibromides or 1,2-bromotriflates. These 1,2
      dimetallic species can undergo Cu or Pd-catalyzed acylations, allylations, or
      cross-couplings.

PMID- 22951988
TI  - A system for ex vivo culturing of embryonic pancreas.
AB  - The pancreas controls vital functions of our body, including the production of
      digestive enzymes and regulation of blood sugar levels. Although in the past
      decade many studies have contributed to a solid foundation for understanding
      pancreatic organogenesis, important gaps persist in our knowledge of early
      pancreas formation. A complete understanding of these early events will provide
      insight into the development of this organ, but also into incurable diseases that
      target the pancreas, such as diabetes or pancreatic cancer. Finally, this
      information will generate a blueprint for developing cell-replacement therapies
      in the context of diabetes. During embryogenesis, the pancreas originates from
      distinct embryonic outgrowths of the dorsal and ventral foregut endoderm at
      embryonic day (E) 9.5 in the mouse embryo. Both outgrowths evaginate into the
      surrounding mesenchyme as solid epithelial buds, which undergo proliferation,
      branching and differentiation to generate a fully mature organ. Recent evidences
      have suggested that growth and differentiation of pancreatic cell lineages,
      including the insulin-producing beta-cells, depends on proper tissue
      architecture, epithelial remodeling and cell positioning within the branching
      pancreatic epithelium. However, how branching morphogenesis occurs and is
      coordinated with proliferation and differentiation in the pancreas is largely
      unknown. This is in part due to the fact that current knowledge about these
      developmental processes has relied almost exclusively on analysis of fixed
      specimens, while morphogenetic events are highly dynamic. Here, we report a
      method for dissecting and culturing mouse embryonic pancreatic buds ex vivo on
      glass bottom dishes, which allow direct visualization of the developing pancreas
      (Figure 1). This culture system is ideally devised for confocal laser scanning
      microscopy and, in particular, live-cell imaging. Pancreatic explants can be
      prepared not only from wild-type mouse embryos, but also from genetically
      engineered mouse strains (e.g. transgenic or knockout), allowing real-time
      studies of mutant phenotypes. Moreover, this ex vivo culture system is valuable
      to study the effects of chemical compounds on pancreatic development, enabling to
      obtain quantitative data about proliferation and growth, elongation, branching,
      tubulogenesis and differentiation. In conclusion, the development of an ex vivo
      pancreatic explant culture method combined with high-resolution imaging provides
      a strong platform for observing morphogenetic and differentiation events as they
      occur within the developing mouse embryo.

PMID- 22951989
TI  - Autophagy in clear cell ovarian cancer, a potential marker for hypoxia and poor
      prognosis?(#).
AB  - Autophagy contributes to cell survival and is up-regulated under hypoxia in many
      different cancers. Ovarian cancer has a poor prognosis and is generally resistant
      to chemotherapy. Through genetic profiling, it has becoming evident that ovarian
      cancer has distinct subtypes but the significance of these subtypes in ovarian
      cancer remains unclear. In this issue, Dr Lum and colleagues have presented
      evidence that autophagy as measured by LC3A staining occurs in a clear cell
      ovarian cancer that is correlated with hypoxic regions and poor overall survival.
      In addition, autophagy under hypoxia appears to be higher in clear cell ovarian
      cancer cells compared to other subtypes. This indicates that autophagy could be a
      factor in drug resistance and poor survival in clear cell ovarian cancer
      patients. This insight could lead to a better understanding of the role of
      autophagy under hypoxia in human ovarian cancer and could be a valuable biomarker
      for the development of better therapies for clear cell ovarian cancers.

PMID- 22951990
TI  - Intermolecular electron transfer promoted by directional donor-acceptor
      attractions in self-assembled diketopyrrolopyrrole-thiophene films.
AB  - The photophysics of a symmetric triad consisting of two bithiophene (BT) units
      covalently linked to a central diketopyrrolopyrrole unit (DPP) has been
      investigated both in dichloromethane and in the thin film. The DPP-BT film
      exhibits a red-shifted low-energy absorption band compared to its solution, which
      is indicative of efficient pi-pi interactions in the solid-state phase. The
      steady-state and time-resolved fluorescence results revealed that the
      photoluminescence was subjected to severe emission quenching when DPP-BT changes
      from its solution phase to its film form. Further femtosecond transient
      absorption studies clarified that rapid intermolecular electron transfer accounts
      for the considerable fluorescence quenching event. The structural
      characterization of DPP-BT nanobelts, based on GIXRD and SAED patterns, suggested
      that the composite may be self-assembled into a slipped face-to-face
      configuration in the film, providing compact interlayer D-A interactions. As a
      result, intermolecular electron transfer is promoted by the favorable donor
      acceptor attractions between the adjacent molecules. Moreover, this packing
      configuration provides a moderate channel for charge transportation. The hole
      mobility, which was measured based on a single-belt field-effect transistor, was
      found to be around 0.07 cm(2) V(-1) s(-1). Our observation reveals the role of
      spatial orientation in photophysical processes and the consequential
      semiconductor performance, providing guidance for the development and self
      assembly of new opto-electronic molecules.

PMID- 22951992
TI  - Anion exchange membrane adsorbers for flow-through polishing steps: Part II.
      Virus, host cell protein, DNA clearance, and antibody recovery.
AB  - Anion exchange membrane adsorbers are used for contaminant removal in flow
      through polishing steps in the manufacture of biopharmaceuticals. This
      contribution describes the clearance of minute virus of mice, DNA, and host cell
      proteins by three commercially available anion-exchange membranes: Sartobind Q,
      Mustang Q, and ChromaSorb. The Sartobind Q and Mustang Q products contain
      quaternary amine ligands; whereas, ChromaSorb contains primary amine based
      ligands. Performance was evaluated over a range of solution conditions: 0-200 mM
      NaCl, pH 6.0-9.0, and flow rates of 4-20 membrane volumes/min in the presence and
      absence of up to 50 mM phosphate and acetate. In addition contaminant clearance
      was determined in the presence and absence of 5 g/L monoclonal antibody. The
      quaternary amine based ligands depend mainly on Coulombic interactions for
      removal of negatively charged contaminants. Consequently, performance of
      Sartobind Q and Mustang Q was compromised at high ionic strength. Primary amine
      based ligands in ChromaSorb enable high capacities at high ionic strength due to
      the presence of secondary, hydrogen bonding interactions. However, the presence
      of hydrogen phosphate ions leads to reduced capacity. Monoclonal antibody
      recovery using primary amine based anion-exchange ligands may be lower if
      significant binding occurs due to secondary interactions. The removal of a
      specific contaminant is affected by the level of removal of the other
      contaminants. The results of this study may be used to help guide selection of
      commercially available membrane absorbers for flow-through polishing steps.

PMID- 22951993
TI  - DNA methylation as a mechanism of nutritional plasticity: limited support from
      horned beetles.
AB  - Epigenetic changes to DNA, potentially heritable alterations above the sequence
      level, such as DNA methylation, are thought to underlie many instances of
      adaptive phenotypic plasticity. Our understanding of the links between epigenetic
      variation and adaptive phenotypic plasticity in natural populations is limited.
      If DNA methylation underlies adaptive responses to different nutritional
      environments, methylation patterns should be correlated with differences in
      performance across nutritional environments, and respond to changes in the
      environment. Additionally, genotypes that can cope with a broader range of
      nutritional environments are expected to have greater flexibility in methylation
      patterns. We tested these predictions using horned beetles (genus Onthophagus),
      which can cope with a wide range of variation in larval nutrition. We surveyed
      levels of methylation across several methylated loci in lab-reared beetles
      originating from natural populations using a methylation-specific amplified
      fragment length polymorphism (AFLP) analysis. For less than half the of the loci
      investigated, methylation level was correlated with performance, measured as
      adult body size attained on a given diet, in different nutritional environments,
      with an overall greater effect in males (the more nutritionally plastic sex) than
      females. Methylation levels at most sites were influenced more by genotype (iso
      female line) than by environment (dung type). Only 1 site (of 12) showed a
      significant genotype-by-environment interaction. Taken together, our results
      provide modest support for the hypothesis that DNA methylation underlies
      nutritional plasticity, as only 8-16% of methylated sites conformed to all of our
      predictions.

PMID- 22951994
TI  - Conformational preferences of gas-phase helices: experiment and theory struggle
      to agree: the seven-residue peptide Ac-Phe-(Ala)5-Lys-H+.
AB  - Peptide conformations: IR/UV double-resonance spectroscopy suggested relative
      energies for four peptide conformations (see figure). These results cannot be
      reproduced by any of 19 density functional methods.

PMID- 22951995
TI  - Generation of an immortalized murine brain microvascular endothelial cell line as
      an in vitro blood brain barrier model.
AB  - Epithelial and endothelial cells (EC) are building paracellular barriers which
      protect the tissue from the external and internal environment. The blood-brain
      barrier (BBB) consisting of EC, astrocyte end-feet, pericytes and the basal
      membrane is responsible for the protection and homeostasis of the brain
      parenchyma. In vitro BBB models are common tools to study the structure and
      function of the BBB at the cellular level. A considerable number of different in
      vitro BBB models have been established for research in different laboratories to
      date. Usually, the cells are obtained from bovine, porcine, rat or mouse brain
      tissue (discussed in detail in the review by Wilhelm et al.). Human tissue
      samples are available only in a restricted number of laboratories or companies.
      While primary cell preparations are time consuming and the EC cultures can differ
      from batch to batch, the establishment of immortalized EC lines is the focus of
      scientific interest. Here, we present a method for establishing an immortalized
      brain microvascular EC line from neonatal mouse brain. We describe the procedure
      step-by-step listing the reagents and solutions used. The method established by
      our lab allows the isolation of a homogenous immortalized endothelial cell line
      within four to five weeks. The brain microvascular endothelial cell lines termed
      cEND (from cerebral cortex) and cerebEND (from cerebellar cortex), were isolated
      according to this procedure in the Forster laboratory and have been effectively
      used for explanation of different physiological and pathological processes at the
      BBB. Using cEND and cerebEND we have demonstrated that these cells respond to
      glucocorticoid- and estrogen-treatment as well as to pro-infammatory mediators,
      such as TNFalpha. Moreover, we have studied the pathology of multiple sclerosis
      and hypoxia on the EC-level. The cEND and cerebEND lines can be considered as a
      good tool for studying the structure and function of the BBB, cellular responses
      of ECs to different stimuli or interaction of the EC with lymphocytes or cancer
      cells.

PMID- 22951996
TI  - Natural radioactivity content in soil and indoor air of Chellanam.
AB  - Contribution of terrestrial radiation due to the presence of naturally occurring
      radionuclides in soil and air constitutes a significant component of the
      background radiation exposure to the population. The concentrations of natural
      radionuclides in the soil and indoor air of Chellanam were investigated with an
      aim of evaluating the environmental radioactivity level and radiation hazard to
      the population. Chellanam is in the suburbs of Cochin, with the Arabian Sea in
      the west and the Cochin backwaters in the east. Chellanam is situated at ~25 km
      from the sites of these factories. The data obtained serve as a reference in
      documenting changes to the environmental radioactivity due to technical
      activities. Soil samples were collected from 30 locations of the study area. The
      activity concentrations of (232)Th, (238)U and (40)K in the samples were analysed
      using gamma spectrometry. The gamma dose rates were calculated using conversion
      factors recommended by UNSCEAR [United Nations Scientific Committee on the
      Effects of Atomic Radiation. Sources and effects of ionizing radiation. UNSCEAR
      (2000)]. The ambient radiation exposure rates measured in the area ranged from 74
      to 195 nGy h(-1) with a mean value of 131 nGy h(-1). The significant
      radionuclides being (232)Th, (238)U and (40)K, their activities were used to
      arrive at the absorbed gamma dose rate with a mean value of 131 nGy h(-1) and the
      radium equivalent activity with a mean value of 162 Bq kg(-1). The radon progeny
      levels varied from 0.21 to 1.4 mWL with a mean value of 0.6 mWL. The thoron
      progeny varied from 0.34 to 2.9 mWL with a mean value of 0.85 mWL. The ratio
      between thoron and radon progenies varied from 1.4 to 2.3 with a mean of 1.6. The
      details of the study, analysis and results are discussed.

PMID- 22951997
TI  - Selection of candidate radiation biomarkers in the serum of rats exposed to gamma
      rays by GC/TOFMS-based metabolomics.
AB  - In the study, gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)
      techniques coupled with principal components analysis (PCA) were used to
      investigate metabolite perturbations in the serum of the rats exposed to 0.75, 3
      or 8 Gy gamma rays. Male standard deviation rats were gamma-irradiated at doses
      of 0.75, 3 and 8 Gy (1.9 Gy min(-1)) or sham-irradiated. Serum samples were
      collected over the first 24 h under the exposure to irradiation in order to
      analyse the samples by GC/TOFMS. And multivariate data were analysed by PCA. The
      composition of metabolites in serum yielded distinct metabolomic phenotypes for
      0.75, 3 and 8 Gy at 24 h after irradiation. Nine serum metabolites were
      significantly altered as a result of radiation exposure. Up-regulated metabolites
      included inositol, serine, lysine, glycine, threonine and glycerol; down
      regulated metabolites included isocitrate, gluconic acid and stearic acid. The
      nine metabolites were significantly altered after ionising radiation for they may
      be the potential biomarkers for the diagnosis of radiation injury.

PMID- 22951998
TI  - A standard for absorbed dose rate to water in a 60Co field using a graphite
      calorimeter at the National Metrology Institute of Japan.
AB  - A primary standard for the absorbed dose rate to water in a 60Co radiation field
      has been newly established at the National Metrology Institute of Japan. This
      primary standard combines the calorimetric measurements using a graphite
      calorimeter with the ionometric measurements using a thick-walled graphite cavity
      ionisation chamber. The calorimeter is operated in the constant temperature mode
      using AC Wheatstone bridges. The absorbed dose rate to water was determined to be
      12 mGy s-1 at a point of 1 m from the radiation source and at a water depth of 5
      g cm-2. The uncertainty on the calibration coefficient in terms of the absorbed
      dose to water of an ionisation chamber using this standard was estimated to be
      0.39 % (k=1).

PMID- 22951999
TI  - Guanine-based photonic crystals in fish scales form from an amorphous precursor.
AB  - Starting from disorder: anhydrous guanine crystals compose the photonic arrays
      responsible for the skin and scale iridescence found in Japanese Koi fish. These
      guanine crystals were found to form in intracellular vesicles through an
      amorphous precursor phase. A combined cryo-SEM and synchrotron radiation X-ray
      diffraction study showed the evolution of the crystals in great detail.

PMID- 22952000
TI  - Notch3 and kidney injury: never two without three.
AB  - Notch receptors and their canonical ligands are transmembrane proteins of the EGF
      like family, expressed in the cell surface. Notch receptors are synthesized as
      single peptides and undergo three sequential proteolytic cleavage steps before
      rendering an active transcription factor, the Notch intracellular domain (NICD).
      Ligand binding facilitates release of NICD by gamma-secretase. Evidence for the
      role of the Notch pathway in kidney injury comes from studies on activation of
      Notch by canonical ligands in cultured cells, on inhibition/targeting of gamma
      secretase in culture or in vivo, on genetic deletion of common Notch pathway
      proteins such as CSL, or descriptions of increased transcription of Notch target
      genes in kidney injury. Inhibitors of gamma-secretase prevent fibrosis in
      experimental kidney injury. However, these drugs may modulate other signalling
      systems beyond Notch and are toxic in human trials. Information regarding the
      specific contribution of each receptor to kidney injury may help design better
      targeted therapeutic approaches. In this regard, overexpression of NICD1, NCID2,
      NICD3 or NICD4 elicits biological responses in cultured renal cells that include
      cell proliferation, apoptosis, and inflammatory and profibrotic responses,
      depending on the particular NICD. Furthermore, immunostaining for NICD1, NICD2,
      and NICD4 suggestive of receptor activation has been observed in glomerular and
      tubular cells in human and experimental kidney disease. Delayed conditional
      Notch1 or Notch2 inactivation facilitates cyst formation, and NICD1
      overexpression in podocytes or tubular cells promotes glomerulosclerosis and
      interstitial fibrosis. Kidney injury is a feature of human Notch2 mutations and
      CADASIL patients with mutated Notch3 may display renal injury. Notch3-/- mice
      display increased sensitivity to angiotensin II-induced kidney injury but are
      less sensitive to tubular injury, inflammation, and fibrosis following unilateral
      ureteral obstruction. The recent availability of blocking antibodies specific for
      Notch1, Notch2, and Notch3 may help to elucidate the therapeutic potential of
      specific targeting of individual Notch receptors in kidney disease.

PMID- 22952001
TI  - Outcome of per oral wide excision of T1-2 N0 localized squamous cell cancer of
      the buccal mucosa--analysis of 156 cases.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of the study was to study the outcomes of per
      oral wide excision of early T1-2 N0 squamous cell cancer of buccal mucosa.
      METHODS: This is a retrospective study of early and localized squamous cell
      cancer of the buccal mucosa treated with peroral wide excision at a tertiary-care
      hospital. RESULTS: A total of 156 patients were analyzed. One hundred ten
      patients (70.5%) had no recurrence, whereas 15 (9.6%) had a local recurrence, 24
      (15.4%) had regional metastasis, three (1.9%) had locoregional recurrence, and
      four (2.6%) developed second primary tumors over a median follow-up of 48 months.
      Most patients with local recurrences (14 patients, 93.3%) and regional metastases
      (24 patients, 100%) could be salvaged with treatment. In contrast, all three
      cases with locoregional could not be salvaged. Most of the cases with
      recurrences, 36 (78%) in this study group, occurred within 2 years of primary
      treatment. Out of 143 cases with a habit of tobacco/beetel quid chewing,
      premalignancy was seen in 62 (43.4%) cases, showing a statistically significant
      association with P-value of 0.012. Fifteen (21.4%) cases with stage T2 developed
      regional neck nodes, while only 9 (10.5%) cases with stage T1 developed regional
      neck nodes with P-value of 0.032. Three-year overall survival rate and disease
      free survival rates were 91.7% and 70.5%, respectively. CONCLUSIONS: Peroral wide
      excision seems to be an adequate procedure for T1-2N0 localized squamous cancer
      of buccal mucosa. Prophylactic selective neck dissection should be considered in
      only T2 N0 cases as only T stage of the disease could be significantly correlated
      with the development of the metastatic neck nodes.

PMID- 22952002
TI  - Werner coordination chemistry and neurodegeneration.
AB  - Neurodegenerative diseases are capturing the world's attention as being the next
      set of diseases we must tackle collectively. Not only are the patients
      experiencing gradual cognitive and physical decline in most cases, but these
      diseases are fatal with no prevention currently available. As these diseases are
      progressive, providing care and symptom treatment for the ageing population is
      becoming both a medical and a financial challenge. This review discusses how
      Werner coordination chemistry plays a role in three diseases - those of
      Alzheimer's, Parkinson's, and prions. Metal ions are considered to be involved in
      these diseases in part via their propensity to cause toxic aggregation of
      proteins. First, the coordination of metal ions, with emphasis on copper(II), to
      metalloproteins that are hallmarks of these diseases - amyloid beta, alpha
      synuclein, and prion, respectively - will be discussed. We will present the
      current understanding of the metal coordination environments created by the amino
      acids of these proteins, as well as metal binding affinity. Second, a diverse set
      of examples of rationally designed metal chelators to outcompete this deleterious
      binding will be examined based on coordination mode and affinity toward bio
      relevant metal ions. Overall, this review will give a general overview of protein
      and metal chelator coordination environments in neurodegenerative diseases.

PMID- 22952003
TI  - Altered feeding differentially regulates circadian rhythms and energy metabolism
      in liver and muscle of rats.
AB  - Energy metabolism follows a diurnal pattern responding to the light/dark cycle
      and food availability. This study investigated the impact of restricting feeding
      to the daylight hours and feeding a high fat diet on circadian clock (bmal1, dbp,
      tef and e4bp4) and metabolic (pepck, fas, ucp3, pdk4) gene expression and markers
      of energy metabolism in muscle and liver of rats. The results show that in chow
      fed rats switched to daylight feeding, the peak diurnal expression of genes in
      liver was shifted by 6-12h while expression of these genes in muscle remained in
      a similar phase to rats feeding ad libitum. High fat feeding during the daylight
      hours had limited effect on clock gene expression in liver or muscle but shifted
      the peak expression of metabolic genes (pepck, fas) in liver by 6-12h. The
      differential effects of daylight feeding on gene and protein expression in muscle
      and liver were accompanied by an 8% reduction in whole body energy expenditure, a
      20-30% increased glycogen content during the light phase in muscle of day-fed
      rats and increased adipose tissue deposition per gram food consumed. These data
      demonstrate that a mismatch of feeding and light/dark cycle disrupts tissue
      metabolism in muscle with significant consequences for whole body energy
      homeostasis.

PMID- 22952005
TI  - High-throughput purification of affinity-tagged recombinant proteins.
AB  - X-ray crystallography is the method of choice for obtaining a detailed view of
      the structure of proteins. Such studies need to be complemented by further
      biochemical analyses to obtain detailed insights into structure/function
      relationships. Advances in oligonucleotide- and gene synthesis technology make
      large-scale mutagenesis strategies increasingly feasible, including the
      substitution of target residues by all 19 other amino acids. Gain- or loss-of
      function phenotypes then allow systematic conclusions to be drawn, such as the
      contribution of particular residues to catalytic activity, protein stability
      and/or protein-protein interaction specificity. In order to attribute the
      different phenotypes to the nature of the mutation--rather than to fluctuating
      experimental conditions--it is vital to purify and analyse the proteins in a
      controlled and reproducible manner. High-throughput strategies and the automation
      of manual protocols on robotic liquid-handling platforms have created
      opportunities to perform such complex molecular biological procedures with little
      human intervention and minimal error rates. Here, we present a general method for
      the purification of His-tagged recombinant proteins in a high-throughput manner.
      In a recent study, we applied this method to a detailed structure-function
      investigation of TFIIB, a component of the basal transcription machinery. TFIIB
      is indispensable for promoter-directed transcription in vitro and is essential
      for the recruitment of RNA polymerase into a preinitiation complex. TFIIB
      contains a flexible linker domain that penetrates the active site cleft of RNA
      polymerase. This linker domain confers two biochemically quantifiable activities
      on TFIIB, namely (i) the stimulation of the catalytic activity during the
      'abortive' stage of transcript initiation, and (ii) an additional contribution to
      the specific recruitment of RNA polymerase into the preinitiation complex. We
      exploited the high-throughput purification method to generate single, double and
      triple substitution and deletions mutations within the TFIIB linker and to
      subsequently analyse them in functional assays for their stimulation effect on
      the catalytic activity of RNA polymerase. Altogether, we generated, purified and
      analysed 381 mutants--a task which would have been time-consuming and laborious
      to perform manually. We produced and assayed the proteins in multiplicates which
      allowed us to appreciate any experimental variations and gave us a clear idea of
      the reproducibility of our results. This method serves as a generic protocol for
      the purification of His-tagged proteins and has been successfully used to purify
      other recombinant proteins. It is currently optimised for the purification of 24
      proteins but can be adapted to purify up to 96 proteins.

PMID- 22952006
TI  - Cardiac myocytes' dynamic contractile behavior differs depending on heart
      segment.
AB  - Cardiac myocytes originating from different parts of the heart exhibit varying
      morphology and ultrastructure. However, the difference in their dynamic behavior
      is unclear. We examined the contraction of cardiac myocytes originating from the
      apex, ventricle, and atrium, and found that their dynamic behavior, such as
      amplitude and frequency of contraction, differs depending on the heart segment of
      origin. Using video microscopy and high-precision image correlation, we found
      that: (1) apex myocytes exhibited the highest contraction rate (~17 beats/min);
      (2) ventricular myocytes exhibited the highest contraction amplitude (~5.2
      micron); and (3) as myocyte contraction synchronized, their frequency did not
      change significantly, but the amplitude of contraction increased in apex and
      ventricular myocytes. In addition, as myocyte cultures mature they formed
      contractile filaments, further emphasizing the difference in myocyte dynamics is
      persistent. These results suggest that the dynamic behavior (in addition to
      static properties) of myocytes is dependent on their segment of origin.

PMID- 22952004
TI  - Impact of obesity on IL-12 family gene expression in insulin responsive tissues.
AB  - Mounting evidence has established a role for chronic inflammation in the
      development of obesity-induced insulin resistance, as genetic ablation of pro
      inflammatory cytokines and chemokines elevated in obesity improves insulin
      signaling in vitro and in vivo. Recent evidence further highlights interleukin
      (IL)-12 family cytokines as prospective inflammatory mediators linking obesity to
      insulin resistance. In this study, we present empirical evidence demonstrating
      that IL-12 family related genes are expressed and regulated in insulin-responsive
      tissues under conditions of obesity. First, we report that respective mRNAs for
      each of the known members of this cytokine family are expressed within detectable
      ranges in WAT, skeletal muscle, liver and heart. Second, we show that these
      cytokines and their cognate receptors are divergently regulated with genetic
      obesity in a tissue-specific manner. Third, we demonstrate that select IL-12
      family cytokines are regulated in WAT in a manner that is dependent on the
      developmental stage of obesity as well as the inflammatory progression associated
      with obesity. Fourth, we report that respective mRNAs for IL-12 cytokines and
      receptors are also expressed and divergently regulated in cultured adipocytes
      under conditions of inflammatory stress. To our knowledge, this report is the
      first study to systemically evaluated mRNA expression of all IL-12 family
      cytokines and receptors in any tissue under conditions of obesity highlighting
      select family members as potential mediators linking excess nutrient intake to
      metabolic diseases such as insulin resistance, diabetes and heart disease.

PMID- 22952007
TI  - Influence of age on postural compensation after unilateral deafferentation due to
      vestibular schwannoma surgery.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the age-related effects of vestibular
      schwannoma (VS) on postural control and whether the postoperative postural
      strategies differ according to age. STUDY DESIGN: Longitudinal, transversal
      study. METHODS: Forty-seven VS patients were split into three groups according to
      age (group I, 14 patients aged from 30 to 44 years; group II, 21 patients aged
      from 45 to 59 years; and group III, 12 patients aged from 60 to 75 years). All
      patients underwent vestibular and posturographic testing shortly before as well
      as 8 days and 3 months after surgical tumor removal. RESULTS: Vestibular and
      postural performance followed a classical time course with degradation just after
      surgery and recovery 3 months after surgery, whatever the age group. However, in
      the elderly the improvement of postural performances compared to preoperatively
      was more important, especially in conflicting situations. CONCLUSIONS: Despite of
      age-related decline in postural control and cognitive processes, neuroplasticity
      allowed not only a recovery but even an improvement of balance after surgical VS
      removal in the elderly. This study highlights the interest of VS surgery even at
      a more advanced age.

PMID- 22952008
TI  - Patients with polymorphic light eruption have decreased serum levels of 25
      hydroxyvitamin-D3 that increase upon 311 nm UVB photohardening.
AB  - BACKGROUND: Polymorphic light eruption (PLE) is a very common condition whose
      pathogenesis may involve immunological abnormalities. Vitamin D sufficiency is
      thought to be important for normal immune function. OBJECTIVE: To determine
      whether PLE patients are vitamin D deficient and to study how photohardening with
      311 nm UVB affects the vitamin D status of PLE patients. METHODS: The vitamin D
      status of 23 PLE patients (21 females and 2 males; age range, 18-55 years) was
      analysed at four different time points (early spring, late spring, summer, and
      winter) by measuring 25-hydroxyvitamin-D(3) (25(OH)D) serum levels through a
      standardised immunoassay. Fifteen of those patients received 311 nm UVB in early
      spring for prevention of PLE symptoms. 25(OH)D levels of the PLE patients were
      compared to that of 23 sex-, age-, and body-mass-index post hoc-matched control
      subjects. RESULTS: PLE patients had low levels of 25(OH)D throughout the year
      compared to that of the control subjects. At baseline in early spring, the mean
      +/- SD 25(OH)D level was 14.9 +/- 3.0 ng ml(-1) in the PLE patients that would
      later receive 311 nm UVB and 14.4 +/- 2.4 ng ml(-1) in the patients not receiving
      311 nm UVB. Successful prophylactic treatment with 311 nm UVB significantly
      increased 25(OH)D levels to a mean of 21.0 +/- 3.4 ng ml(-1) (p < 0.001; ANOVA,
      Tukey's test). Heading into summer, the 25(OH)D levels in treated patients
      decreased again, reaching their lowest levels in winter. In contrast, the 25(OH)D
      levels of untreated PLE patients stayed in the low range in early and late spring
      but increased by trend towards summer, reaching similar levels to that of the PLE
      patients who had received 311 nm UVB (17.1 +/- 2.3 vs. 17.3 +/- 6.0 ng ml(-1)).
      Like the treated PLE patients, 25(OH)D levels of untreated patients significantly
      decreased in winter to comparable levels (12.2 +/- 1.9 vs. 13.8 +/- 1.8 ng ml(
      1)). Taken together, the 25(OH)D levels of PLE patients were significantly lower
      at all time points than that observed in the matched control population (34.4 +/-
      12.5 ng ml(-1)) (p < 0.000003). CONCLUSIONS: PLE patients have low 25(OH)D serum
      levels. 311 nm UVB phototherapy that prevented PLE symptoms increased those
      levels. Thus, we speculate that boosting levels of vitamin D may be important in
      ameliorating PLE.

PMID- 22952009
TI  - Preparation of 2-azido-1-substituted-1H-benzo[d]imidazoles using a copper
      promoted three-component reaction and their further conversion into 2-amino and 2
      triazolyl derivatives.

PMID- 22952010
TI  - Angiogenesis: The new normal.

PMID- 22952012
TI  - Design and synthesis of 3-carbamoylbenzoic acid derivatives as inhibitors of
      human apurinic/apyrimidinic endonuclease 1 (APE1).
AB  - Apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is a multifaceted protein with
      an essential role in the base excision repair (BER) pathway. Its implication in
      tumor development, progression, and resistance has been confirmed in multiple
      cancers, making it a viable target for intensive investigation. In this work, we
      designed and synthesized different classes of small-molecule inhibitors of the
      catalytic endonuclease function of APE1 that contain a 3-carbamoylbenzoic acid
      scaffold. Further structural modifications were made with the aim of increasing
      the activity and cytotoxicity of these inhibitors. Several of our compounds were
      shown to inhibit the catalytic endonuclease function of APE1 with potencies in
      the low-micromolar range in vitro, and therefore represent novel classes of APE1
      inhibitors worthy of further development.

PMID- 22952013
TI  - Light-regulated host-guest interaction as a new strategy for intracellular PEG
      detachable polyplexes to facilitate nuclear entry.
AB  - PEG-detachable polyplexes were constructed for the first time via host-guest
      interactions between beta-cyclodextrin and azobenzene. The polyplexes had
      excellent colloidal stability and competition stability. Moreover, the
      intracellular light-regulated dePEGylation facilitated DNA release and nuclear
      entry, thus resulting in efficient transfection.

PMID- 22952014
TI  - Pharmacological and pathophysiological roles of carnitine/organic cation
      transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21).
AB  - The carnitine/organic cation transporter (OCTN) family consists of three
      transporter isoforms, i.e. OCTN1 (SLC22A4) and OCTN2 (SLC22A5) in humans and
      animals and Octn3 (Slc22a21) in mice. These transporters are physiologically
      essential to maintain appropriate systemic and tissue concentrations of carnitine
      by regulating its membrane transport during intestinal absorption, tissue
      distribution and renal reabsorption. Among them, OCTN2 is a sodium-dependent,
      high-affinity transporter of carnitine, and a functional defect of OCTN2 due to
      genetic mutation causes primary systemic carnitine deficiency (SCD). Since
      carnitine is essential for beta-oxidation of long-chain fatty acids to produce
      ATP, OCTN2 gene mutation causes a range of symptoms, including cardiomyopathy,
      skeletal muscle weakness, fatty liver and male infertility. These functional
      consequences of Octn2 gene mutation can be seen clearly in an animal model, jvs
      mouse, which exhibits the SCD phenotype. In addition, although the mechanism is
      not clear, single nucleotide polymorphisms of OCTN1 and OCTN2 genes are
      associated with increased incidences of rheumatoid arthritis, Crohn's disease and
      asthma. OCTN1 and OCTN2 accept cationic drugs as substrates and contribute to
      intestinal and pulmonary absorption, tissue distribution (including to tumour
      cells), and renal excretion of these drugs. Modulation of the transport activity
      of OCTN2 by externally administered drugs may cause drug-induced secondary
      carnitine deficiency. Rodent Octn3 transports carnitine specifically,
      particularly in male reproductive tissues. Thus, the OCTNs are physiologically,
      pathologically and pharmacologically important. Detailed characterization of
      these transporters will greatly improve our understanding of the pathology
      associated with common diseases caused by functional deficiency of OCTNs.

PMID- 22952011
TI  - Crosstalk between chromatin state and DNA damage response in cellular senescence
      and cancer.
AB  - The generation of DNA lesions and the resulting activation of DNA damage response
      (DDR) pathways are both affected by the chromatin status at the site of damaged
      DNA. In turn, DDR activation affects the chromatin at both the damaged site and
      across the whole genome. Cellular senescence and cancer are associated with the
      engagement of the DDR pathways and with profound chromatin changes. In this
      Opinion article, we discuss the interplay between chromatin and DDR factors in
      the context of cellular senescence that is induced by oncogenes and in cancer.

PMID- 22952015
TI  - Observation of subcellular metabolite gradients in single cells by laser ablation
      electrospray ionization mass spectrometry.

PMID- 22952016
TI  - Quantitative measurement of invadopodia-mediated extracellular matrix proteolysis
      in single and multicellular contexts.
AB  - Cellular invasion into local tissues is a process important in development and
      homeostasis. Malregulated invasion and subsequent cell movement is characteristic
      of multiple pathological processes, including inflammation, cardiovascular
      disease and tumor cell metastasis. Focalized proteolytic degradation of
      extracellular matrix (ECM) components in the epithelial or endothelial basement
      membrane is a critical step in initiating cellular invasion. In tumor cells,
      extensive in vitro analysis has determined that ECM degradation is accomplished
      by ventral actin-rich membrane protrusive structures termed invadopodia.
      Invadopodia form in close apposition to the ECM, where they moderate ECM
      breakdown through the action of matrix metalloproteinases (MMPs). The ability of
      tumor cells to form invadopodia directly correlates with the ability to invade
      into local stroma and associated vascular components. Visualization of
      invadopodia-mediated ECM degradation of cells by fluorescent microscopy using dye
      labeled matrix proteins coated onto glass coverslips has emerged as the most
      prevalent technique for evaluating the degree of matrix proteolysis and cellular
      invasive potential. Here we describe a version of the standard method for
      generating fluorescently-labeled glass coverslips utilizing a commercially
      available Oregon Green-488 gelatin conjugate. This method is easily scaled to
      rapidly produce large numbers of coated coverslips. We show some of the common
      microscopic artifacts that are often encountered during this procedure and how
      these can be avoided. Finally, we describe standardized methods using readily
      available computer software to allow quantification of labeled gelatin matrix
      degradation mediated by individual cells and by entire cellular populations. The
      described procedures provide the ability to accurately and reproducibly monitor
      invadopodia activity, and can also serve as a platform for evaluating the
      efficacy of modulating protein expression or testing of anti-invasive compounds
      on extracellular matrix degradation in single and multicellular settings.

PMID- 22952017
TI  - Production of 3-hydroxypropionic acid from glycerol by recombinant Klebsiella
      pneumoniae DeltadhaTDeltayqhD which can produce vitamin B12 naturally.
AB  - 3-Hydroxypropionic acid (3-HP) is an important platform chemical that can be used
      to synthesize a range of chemical compounds. A previous study demonstrated that
      recombinant Escherichia coli stains can produce 3-HP from glycerol in the
      presence of vitamin B12 (coenzyme B12), when overexpressed with a coenzyme B12
      dependent glycerol dehydratase (DhaB) and an aldehyde dehydrogenase. The present
      study examined the production of 3-HP in recombinant Klebsiella pneumoniae
      strains, which naturally synthesizes vitamin B12 and does not require
      supplementation of the expensive vitamin. The NAD+-dependent gamma-glutamyl-gamma
      aminobutyraldehyde dehydrogenase (PuuC) of K. pneumoniae alone or with its DhaB
      was overexpressed homologously, and two major oxidoreductases, DhaT and YqhD,
      were disrupted. Without vitamin B12 addition, the recombinant K. pneumoniae
      DeltadhaTDeltayqhD overexpressing PuuC could produce ~3.8 g/L 3-HP in 12 h of
      flask culture. However, this was possible only under the appropriate aeration
      conditions; 1,3-propanediol (1,3-PDO) (instead of 3-HP) was mainly produced when
      aeration was insufficient, whereas a very small amount of both 3-HP and 1,3-PDO
      were produced when aeration was too high. The production of a small amount of 3
      HP under improper aeration conditions was attributed to either slow NAD+
      regeneration (under low aeration) or reduced vitamin B12 synthesis (under high
      aeration). In a glycerol fed-batch bioreactor experiment under a constant DO of
      5%, the strain, K. pneumoniae DeltadhaTDeltayqhD, overexpressing both PuuC and
      DhaB could produce >28 g/L 3-HP in 48 h with a yield of >40% on glycerol. Only
      small amount of 3-HP was produced when cultivation was carried out at a constant
      aeration of 1 vvm or constant 10% DO. These results show that K. pneumoniae is
      potentially useful for the production of 3-HP in an economical culture medium
      that does not require vitamin B12. The results also suggest that the aeration
      conditions should be optimized carefully for the efficient production of 3-HP
      while using this strain.

PMID- 22952018
TI  - The endoscopic-assisted trephination approach for repair of frontal sinus
      cerebrospinal fluid leaks.

PMID- 22952019
TI  - Adults with diabetes who perceive family members' behaviour as unsupportive are
      less adherent to their medication regimen.

PMID- 22952020
TI  - Breastfeeding duration not associated with average adiposity levels in 6-year
      olds to 13-year-olds, but adequate breastfeeding may be associated with lower
      adiposity in the upper percentiles.

PMID- 22952021
TI  - Patient perception of nurse-led chronic disease management varies depending on
      whether this was previously familiar to them.

PMID- 22952022
TI  - New insights into cinchonine-aluminium complexes and their application as chiral
      building blocks: unprecedented ligand-exchange processes in the presence of ZnR2
      compounds.
AB  - Previous studies have demonstrated that [(CN)(2)AlCl] and [R(2)Al(MU-CN)](2)
      (CN=deprotonated cinchonine) complexes can effectively act as chiral, semirigid,
      N,N-ditopic metalloligands for Zn-containing nodes, and provide viable means for
      constructing new, homochiral, heterometallic, coordination polymers of zigzag and
      helical topologies. These findings have prompted further investigations on the
      organometallic analogues of the formula [(CN)(2)AlR], anticipating their utility
      as N,N-metalloligands for ZnR(2) units. Surprisingly, reactions of [(CN)(2)AlMe]
      type metalloligands with ZnR(2) compounds (R=Me or Et) revealed unprecedented
      ligand-exchange processes, including zinc-to-aluminium and aluminium-to-zinc
      transmetalations of alkyl groups. The molecular and crystal structure of the
      resulting compounds was determined by X-ray diffraction analysis. From the
      reaction of [(CN)(2)AlMe] with ZnMe(2) a new pseudopolymorphic form of a
      noncovalent porous material based on [Me(2)Al(MU-CN)](2) molecules was isolated.
      Strikingly, the analogous reaction involving ZnEt(2) led to the generation of a
      new chiral 4N-tetratopic heterometalloligand [(CN)EtAl(MU-CN)(2)ZnEt]. The latter
      unit was successfully connected by alkyl-exchanged ZnMe(2) nodes to give an
      original homochiral heterometallic {[(CN)EtAl(MU-CN)(2)ZnEt]ZnMe(2)}(n)
      coordination polymer adopting a snake 1D motif. The outcome of the revealed
      reactions indicates the complicated multistep reaction route that involves
      redistribution of cinchonine and alkyl ligands among the Al and Zn centers, and a
      general reaction scheme is proposed. The results are in strong contrast with the
      previously studied inorganic-organic [(CN)(2)AlCl/ZnCl(2)] system, which
      exclusively affords a helical coordination polymer based on ZnCl(2) nodes and
      (CN)(2)AlCl metalloligands and lacks the exchange of CN ligands.

PMID- 22952023
TI  - A liposomal system capable of generating CO2 bubbles to induce transient
      cavitation, lysosomal rupturing, and cell necrosis.

PMID- 22952024
TI  - The interplay between hydrogen bonding and pi-pi stacking interactions in the
      crystal packing of N1-thyminyl derivatives, and implications for the photo
      chemical [2pi + 2pi]-cycloaddition of thyminyl compounds.
AB  - The solid-state photo-chemical dimerisation of thyminyl derivatives occurs when
      two thyminyl units are aligned in such a way that the olefinic moieties are
      separated by a distance of less than 4.2 A. When irradiated with >270 nm UV, the
      thyminyl olefinic groups undergo [2pi + 2pi]-cycloaddition to form a dimeric
      cyclobutane derivative. However, the design and execution of [2pi + 2pi]
      cycloaddition reactions can be challenging due to the requirement to produce
      molecular crystals with the necessary olefinic alignment. In this investigation,
      the crystallographic and solid-state photo-chemical reactions of six N1-thyminyl
      derivatives are studied. Only one derivative, thyminyl propanamide (), was found
      to undergo [2pi + 2pi]-cycloaddition in the crystalline state. As such, quantum
      chemical methods were employed to study the photo-chemical transition states of
      the derivatives, as well as the strengths of typical intermolecular interactions
      that were observed in their crystal structures (such as pi-pi stacking between
      the thyminyl rings, Watson and Crick style hydrogen bonding and hydrogen bonding
      between functional groups of N1 substituents). These results were used to
      rationalise the solid-state photo-reactivity of more complex bis-thyminyl
      monomers.

PMID- 22952025
TI  - The role of the reactor wall in hydrothermal biomass conversions.
AB  - The processing of renewable feedstocks to platform chemicals and, to a lesser
      degree, fuels is a key part of sustainable development. In particular, the
      combination of lignocellulosic biomass with hydrothermal upgrading (HTU), using
      high temperature and pressure water (HTPW), is experiencing a renaissance. One of
      the many steps in this complicated process is the in-situ hydrogenation of
      intermediate compounds. As formic acid and related low-molecular-weight
      oxygenates are among the species generated, it is conceivable that they act as a
      hydrogen source. Such hydrogenations have been suggested to be catalyzed by
      water, by bases like NaOH, and/or to involve "reactive/nascent hydrogen". To
      achieve the temperatures and pressures required for HTU, it is necessary to
      conduct the reactions in high-pressure vessels. Metals are typical components of
      their walls and/or internal fittings. Here, using cyclohexanone as a model
      compound for more complex biomass-derived molecules, iron in the wall of high
      pressure stainless steel reactors is shown to be responsible for the
      hydrogenation of ketones with low-molecular-weight oxygenates acting as a
      hydrogen source in combination with water.

PMID- 22952026
TI  - Generation, purification, and characterization of cell-invasive DISC1 protein
      species.
AB  - Protein aggregation is seen as a general hallmark of chronic, degenerative brain
      conditions like, for example, in the neurodegenerative diseases Alzheimer's
      disease (Abeta, tau), Parkinson's Disease (alpha-synuclein), Huntington's disease
      (polyglutamine, huntingtin), and others. Protein aggregation is thought to occur
      due to disturbed proteostasis, i.e. the imbalance between the arising and
      degradation of misfolded proteins. Of note, the same proteins are found
      aggregated in sporadic forms of these diseases that are mutant in rare variants
      of familial forms. Schizophrenia is a chronic progressive brain condition that in
      many cases goes along with a permanent and irreversible cognitive deficit. In a
      candidate gene approach, we investigated whether Disrupted-in-schizophrenia 1
      (DISC1), a gene cloned in a Scottish family with linkage to chronic mental
      disease, could be found as insoluble aggregates in the brain of sporadic cases of
      schizophrenia. Using the SMRI CC, we identified in approximately 20% of cases
      with CMD but not normal controls or patients with neurodegenerative diseases
      sarkosyl-insoluble DISC1 immunoreactivity after biochemical fractionation.
      Subsequent studies in vitro revealed that the aggregation propensity of DISC1 was
      influenced by disease-associated polymorphism S704C, and that DISC1 aggresomes
      generated in vitro were cell-invasive, similar to what had been shown for Abeta,
      tau, alpha-synuclein, polyglutamine, or SOD1 aggregates. These findings prompted
      us to propose that at least a subset of cases with CMD, those with aggregated
      DISC1 might be protein conformational disorders. Here we describe how we generate
      DISC1 aggresomes in mammalian cells, purify them on a sucrose gradient and use
      them for cell-invasiveness studies. Similarly, we describe how we generate an
      exclusively multimeric C-terminal DISC1 fragment, label and purify it for cell
      invasiveness studies. Using the recombinant multimers of DISC1 we achieve similar
      cell invasiveness as for a similarly labeled synthetic alpha-synuclein fragment.
      We also show that this fragment is taken up in vivo when stereotactically
      injected into the brain of recipient animals.

PMID- 22952027
TI  - Changing microbiology of pediatric neck abscesses in Iowa 2000-2010.
AB  - OBJECTIVES/HYPOTHESIS: To examine the changing microbiology of pediatric neck
      abscesses over a 10-year period with particular interest in methicillin-resistant
      Staphylococcus aureus (MRSA) infections and their associated antibacterial
      resistance patterns, including resistance to clindamycin, a frequently used
      antibiotic for Staphylococcus aureus. STUDY DESIGN: Retrospective chart review at
      a tertiary academic medical center. METHODS: One hundred and twenty-two
      consecutive pediatric patients managed between January 2000 and June 2010 with
      incision and drainage of a proven neck abscess. RESULTS: Seventy-four patients
      with 76 abscesses were identified. A microorganism was found in 65 (85%) of the
      76 abscesses. Forty-three percent grew Staphylococcus aureus (SA), 12% were
      methicillin-resistant Staphylococcus Aureus (MRSA), and 31% were methicillin
      susceptible Staphylococcus aureus (MSSA). There was a significant increase in the
      incidence of MRSA infections during the study period, with only one case of MRSA
      diagnosed in the first half of the study (from 2000-2004) compared with seven in
      the second half (from 2005-2010) (P = 0.023). The second most common bacterial
      etiology or isolate was Streptococcus pyogenes in 27%, while the remaining 30%
      grew mixed oral flora and other microorganisms. CONCLUSIONS: These findings
      demonstrate a statistically significant rise in the proportion of MRSA neck
      infections in pediatric patients in Iowa. Resistance to clindamycin was highest
      among MSSA isolates. Clindamycin-resistant S. aureus and Streptococcus pyogenes
      are established pathogens in neck infections. In communities with similar
      microbiology patterns, empiric treatment with combination therapy of a beta
      lactam and vancomycin or trimethoprim/sulfamethoxazole should be initiated until
      culture results are available.

PMID- 22952028
TI  - Making strides in fighting childhood cancers: researchers at St. Jude Children's
      Research Hospital discuss major advances and key studies in pediatric oncology
      treatments.

PMID- 22952029
TI  - Chemotherapy and radiotherapy combination extends survival for patients with
      oligodendroglial tumors.

PMID- 22952030
TI  - Statins may slow prostate growth.

PMID- 22952032
TI  - Assessment of the pathologic inclusion criteria from contemporary adjuvant
      clinical trials for predicting disease progression after nephrectomy for renal
      cell carcinoma.
AB  - BACKGROUND: The objective of this study was to evaluate the accuracy of the
      pathologic inclusion criteria from all contemporary adjuvant trials in predicting
      disease progression (DP) for renal cell carcinoma (RCC). METHODS: A retrospective
      review was conducted on 1363 patients treated surgically for M0 RCC at the Mayo
      Clinic (Rochester, MN), from 1990 to 2001. Clinicopathologic features were
      reviewed to determine eligibility for the following trials: ARISER, ASSURE,
      EVEREST, PROTECT, SORCE, and S-TRAC. DP was defined as local recurrence or
      distant metastasis after surgery. The ability of each trial's inclusion criteria
      to accurately predict DP was evaluated by the c (concordance) index. RESULTS:
      From the Mayo Clinic cohort, we determined that 41%, 45%, 45%, 33%, 47%, and 23%
      of the patients would have been eligible for the ARISER, ASSURE, EVEREST,
      PROTECT, SORCE, and S-TRAC clinical trials, respectively. Overall, 23% of all
      patients experienced DP (n = 317). Among eligible patients, 53%, 44%, 44%, 57%,
      43%, and 59% developed DP during follow-up and 10%, 6%, 6%, 13%, 6%, and 18% went
      onto DP while not being eligible for the ARISER, ASSURE, EVEREST, PROTECT, SORCE,
      and S-TRAC trials, respectively. The c index of each trial to accurately predict
      DP from the pathologic inclusion criteria of ARISER, ASSURE, EVEREST, PROTECT,
      SORCE, and S-TRAC were 0.751, 0.751, 0.751, 0.742, 0.745, and 0.691,
      respectively. CONCLUSIONS: Although the pathologic inclusion criteria of
      contemporary adjuvant trials have notable differences, all 6 adjuvant trials
      demonstrated high predictive accuracy of DP. Overall, 43% to 59% of patients
      included for the adjuvant trials would develop DP, whereas 6% to 18% of patients
      excluded from the trials would develop DP during follow-up.

PMID- 22952033
TI  - A base-promoted tandem cycloaddition/air oxidation reaction of electron-deficient
      conjugated enynes and hydrazines: synthesis of highly substituted pyrazoles.
AB  - Rapid access: A base-mediated cycloaddition/oxidation reaction of hydrazines and
      electron-deficient 1,3-conjugated enynes gives pyrazole derivatives, some of
      which are not easily accessible by other methods (see scheme). The reaction
      conditions are mild, thus enabling a variety of functional groups to be
      tolerated.

PMID- 22952034
TI  - Efficient dye-sensitized solar cells based on hydroquinone/benzoquinone as a
      bioinspired redox couple.
AB  - A hybrid electrolyte involving tetramethylammonium (TMA)
      hydroquinone/benzoquinone redox couple is formulated. This electrolyte is more
      transparent than the traditional I(-)/I(3)(-) electrolyte and has negligible
      absorption in the visible region. Dye-sensitized solar cells using the hybrid
      electrolyte show higher light-to-electricity conversion efficiency. FTO=fluorine
      doped tin oxide.

PMID- 22952036
TI  - Exploring the myth of nascent hydrogen and its implications for biomass
      conversions.
AB  - Iron (and to a lesser extent manganese) in the wall of a 316 stainless steel (SS)
      reactor is responsible for the hydrogenation of cyclohexanone to cyclohexanol
      when using an aqueous formic acid solution under high temperature and pressure
      water (HTPW) conditions. However, not only dilute formic acid but also aqueous
      solutions of several other organic and mineral acids in the presence of iron are
      active in this reaction covering a range of aldehydes and ketones, even under
      ambient conditions. The stoichiometry, kinetics, and the possible mechanisms of
      both dihydrogen production as well as of the hydrogenation of the model compound
      cyclohexanone were examined. The reduction is essentially stoichiometric with
      respect to metallic iron, and the conversions are highly dependent on the speed
      of stirring as well as temperature and reactant concentrations. Importantly, it
      is established unequivocally that water participates in dihydrogen gas formation
      (hydrogen atoms originate from both the acid and water molecules) and facilitates
      substrate reduction.

PMID- 22952037
TI  - Internet-based cognitive behavioural therapy (FITNET) is an effective treatment
      for adolescents with chronic fatigue syndrome.

PMID- 22952038
TI  - Purification and aggregation of the amyloid precursor protein intracellular
      domain.
AB  - Amyloid precursor protein (APP) is a type I transmembrane protein associated with
      the pathogenesis of Alzheimer's disease (AD). APP is characterized by a large
      extracellular domain and a short cytosolic domain termed the APP intracellular
      domain (AICD). During maturation through the secretory pathway, APP can be
      cleaved by proteases termed alpha, beta, and gamma-secretases. Sequential
      proteolytic cleavage of APP with beta and gamma-secretases leads to the
      production of a small proteolytic peptide, termed Abeta, which is amyloidogenic
      and the core constituent of senile plaques. The AICD is also liberated from the
      membrane after secretase processing, and through interactions with Fe65 and
      Tip60, can translocate to the nucleus to participate in transcription regulation
      of multiple target genes. Protein-protein interactions involving the AICD may
      affect trafficking, processing, and cellular functions of holo-APP and its C
      terminal fragments. We have recently shown that AICD can aggregate in vitro, and
      this process is inhibited by the AD-implicated molecular chaperone ubiquilin-1.
      Consistent with these findings, the AICD has exposed hydrophobic domains and is
      intrinsically disordered in vitro, however it obtains stable secondary structure
      when bound to Fe65. We have proposed that ubiquilin-1 prevents inappropriate
      inter- and intramolecular interactions of AICD, preventing aggregation in vitro
      and in intact cells. While most studies focus on the role of APP in the
      pathogenesis of AD, the role of AICD in this process is not clear. Expression of
      AICD has been shown to induce apoptosis, to modulate signaling pathways, and to
      regulate calcium signaling. Over-expression of AICD and Fe65 in a transgenic
      mouse model induces Alzheimer's like pathology, and recently AICD has been
      detected in brain lysates by western blotting when using appropriate antigen
      retrieval techniques. To facilitate structural, biochemical, and biophysical
      studies of the AICD, we have developed a procedure to produce recombinantly large
      amounts of highly pure AICD protein. We further describe a method for inducing
      the in vitro thermal aggregation of AICD and analysis by atomic force microscopy.
      The methods described are useful for biochemical, biophysical, and structural
      characterization of the AICD and the effects of molecular chaperones on AICD
      aggregation.

PMID- 22952039
TI  - Hydrochlorothiazide and cutaneous T cell lymphoma: prospective analysis and case
      series.
AB  - BACKGROUND: Mycosis fungoides (MF) and leukemic Sezary syndrome (SS) are the most
      common cutaneous T cell lymphomas (CTCL), but their etiology remains unknown.
      After patients were observed with hydrochlorothiazide (HCTZ)-associated CTCL,
      HCTZ was examined as a putative chronic antigen in a cohort of prospectively
      staged patients. METHODS: Demographic and drug exposure data was examined from
      1443 confirmed MF and SS patients. Hypertensive CTCL patients were divided into
      HCTZ users or nonusers for statistical analysis by chi-square and t tests.
      Causality in a case series was rated by the Naranjo Adverse Drug Reaction
      Probability Scale. RESULTS: A total of 815 of 1443 MF and SS patients (56.5%)
      were hypertensive; 205 (25.2%) were taking HCTZ at initial staging. Comparing
      stage of patients who were using or not using HCTZ, the most significant
      difference was between stage I and stage IV (odds ratio of 0.45; 95% confidence
      interval of 0.25-0.78, P = .003), demonstrating reduced likelihood of being stage
      IV in patients who were on HCTZ. Seventy-seven percent of the MF patients on HCTZ
      were stage I. A total of 125 patients of 196 (63.8%) started HCTZ prior to
      developing CTCL lesions, and 35 of 121 (28.0%) started within 1 year of first
      skin rash. Thirty-six of 125 patients (28.8%) experienced complete or partial
      remissions after discontinuing HCTZ. A monoclonal T cell receptor rearrangement
      was detected more frequently in the hypertensive stage I patients not taking HCTZ
      as compared with those who were (55.3% vs 69.1%, P = .032). Three patients were
      rechallenged and developed MF lesions that resolved or improved with
      discontinuation. CONCLUSIONS: HCTZ is commonly prescribed and may be a putative
      antigen in a small subset of early MF patients. Careful drug histories and a
      trial off medication are warranted.

PMID- 22952041
TI  - Effects of PEMF on microcirculation and angiogenesis in a model of acute hindlimb
      ischemia in diabetic rats.
AB  - Hindlimb ischemia is a major complication of diabetic patients due to poor
      neovascularization. Therapy with pulsed electromagnetic fields (PEMF) can promote
      angiogenesis in ischemic lesions. However, the efficacy and therapeutic
      mechanisms of PEMF in diabetes-related hindlimb ischemia are unclear. Sprague
      Dawley rats were injected with streptozocin to induce diabetes, and 10 weeks
      later diabetic rats were subjected to surgical induction of acute hindlimb
      ischemia. The rats were randomized and treated with PEMF, and the blood perfusion
      of individual rats was determined longitudinally by laser Doppler perfusion
      imaging (LDPI). The neovascular density was examined using immunofluorescent
      analysis of CD31 expression and alkaline phosphatase (AP) staining. The levels of
      VEGF, VEGFR, FGF-2, and FGFR1 expression, and ERK 1/2 and P38 phosphorylation in
      the muscles were characterized using enzyme-linked immunosorbent assay (ELISA)
      and Western blot assays. The values of LDPI in the PEMF-treated rats at 14 and 28
      days post surgery were significantly greater than those in the controls,
      accompanied by significantly elevated levels of anti-CD31 and AP staining. The
      relative levels of FGF-2 and FGFR1, but not VEGF and VEGFR expression, and
      ERK1/2, but not P38 phosphorylation, in the muscles of the PEMF-treated rats were
      significantly higher than those in the controls. Our data indicated that PEMF
      enhanced acute hindlimb ischemia-related perfusion and angiogenesis, associated
      with up-regulating FGF-2 expression and activating the ERK1/2 pathway in diabetic
      rats. Therefore, PEMF may be valuable for the treatment of diabetic patients with
      ischemic injury.

PMID- 22952040
TI  - Incidence and clinical implications of ATM aberrations in chronic lymphocytic
      leukemia.
AB  - A subset of chronic lymphocytic leukemia (CLL) carries mutations in ataxia
      telangiectasia mutated (ATM). Such ATM mutations may be particularly relevant in
      the setting of del11q, which invariably results in the deletion of one ATM
      allele. To improve our understanding of the frequency and type of ATM mutations
      that exist in CLL, we resequenced all ATM coding exons in 24 CLL with del11q
      using direct sequencing. We detected two missense mutations, resulting in an ATM
      mutation frequency of 8%; nonsense and frameshift mutations were not identified.
      Given the low ATM mutation frequency detected in this cohort, we proceeded with
      measurements of nonmutational ATM aberrations in CLL through analysis of the
      activation state of ATM in response to external irradiation. The phosphorylation
      state of ATM at Ser-1981 was measured using quantitative immunoblotting in
      purified CLL cells isolated from 251 CLL patients; data were normalized to
      simultaneous measurements of total ATM protein and actin. Resulting p-ATM/ATM and
      p-ATM/actin ratios were subsequently analyzed for prognostic significance
      inclusive and exclusive of TP53 exons 2-10 mutations. From these analyses,
      conducted in a large prospectively enrolled CLL patient cohort, neither the p
      ATM/ATM nor the p-ATM/actin ratios were found to be prognostic for short
      survival. These data in aggregate demonstrate a low frequency of ATM aberrations
      in an unselected CLL cohort and do not support a major prognostic role for ATM
      aberrations in CLL, thus motivating renewed research efforts aimed at
      understanding the pathobiology of 11q deletions in CLL. (c) 2012 Wiley
      Periodicals, Inc.

PMID- 22952042
TI  - Added cancer yield of breast magnetic resonance imaging screening in women with a
      prior history of chest radiation therapy.
AB  - BACKGROUND: Recommendation for breast magnetic resonance imaging (MRI) screening
      for women with a prior history of chest radiation is currently based on expert
      opinion, because existing data are very scant. The objective of this study was to
      evaluate added cancer yield of screening breast MRI in this population. METHODS:
      A retrospective review identified 98 women with a prior history of chest
      radiation therapy who had screening mammography and screening MRI performed at
      the authors' institution between January 2004 and July 2010. Medical records of
      these patients and results of 558 screening studies (296 mammograms and 262 MRI)
      were reviewed. Sensitivity, specificity, positive predictive value, negative
      predictive value, and added cancer yield were calculated. RESULTS: Malignancy was
      diagnosed in 13 patients, invasive cancer was diagnosed in 10 patients, and
      ductal carcinomas in situ was diagnosed in 3 patients. The median latency from
      completion of radiation to detection of the breast cancer was 18 years (range, 8
      37 years). Of the 13 cancers, 12 (92%) were detected by MRI, and 9 (69%) by
      mammography. For mammography, the sensitivity, specificity, positive predictive
      value, and negative predictive value were 69%, 98%, 82%, and 95%, respectively;
      and, for MRI, these values were 92%, 94%, 71%, and 99%, respectively. In 4 of 98
      patients, cancer was diagnosed on MRI only, resulting in an incremental cancer
      detection rate of 4.1% (95% confidence interval, 1.6%-10%). CONCLUSIONS: The
      current results indicated that MRI is a useful adjunct modality for screening
      high-risk women who have a prior history of chest radiation therapy, resulting in
      a 4.1% (4 of 98 women) added cancer detection rate. The authors concluded that
      both MRI and mammography should be used to screen women in this high-risk group.

PMID- 22952043
TI  - Generalized anxiety disorder and the proposed associated symptoms criterion
      change for DSM-5 in a treatment-seeking sample of anxious youth.
AB  - BACKGROUND: A current proposal for the DSM-5 general anxiety disorder (GAD)
      definition is to remove fatigue, difficulty concentrating, irritability, and
      sleep disturbance from the list of associated symptoms, and to require the
      presence of one of two retained symptoms (restlessness or muscle tension) for
      diagnosis. Relevant evaluations in youth to support such a change are sparse.
      METHODS: The present study evaluated patterns and correlates of the DSM-IV GAD
      associated symptoms in a large outpatient sample of anxious youth (N = 650) to
      empirically consider how the proposed diagnostic change might impact the
      prevalence and sample composition of GAD in children. RESULTS: Logistic
      regression found irritability to be the most associated, and restlessness to be
      the least associated, with GAD diagnosis. Fatigue, difficulty concentrating, and
      sleep disturbances-which have each been suggested to be nonspecific to GAD due to
      their prevalence in depression-showed sizable associations with GAD even after
      accounting for depression and attention problems. Among GAD youth, 10.9% would
      not meet the proposed DSM-5 associated symptoms criterion. These children were
      comparable to GAD youth who would meet the proposed criteria with regard to
      clinical severity, symptomatology, and functioning. CONCLUSIONS: A substantial
      proportion of youth with excessive, clinically impairing worry may be left
      unclassified by the DSM-5 if the proposed GAD associated symptoms criterion is
      adopted. Despite support for the proposed criterion change in adult samples, the
      present findings suggest that in children it may increase the false negative
      rate. This calls into question whether the proposed associated symptoms criterion
      is optimal for defining childhood GAD.

PMID- 22952044
TI  - TLE1 is an anoikis regulator and is downregulated by Bit1 in breast cancer cells.
AB  - TLE1 is a Groucho-related transcriptional repressor protein that exerts survival
      and antiapoptotic function in several cellular systems and has been implicated in
      the pathogenesis of cancer. In the present study, we found that TLE1 is a
      regulator of anoikis in normal mammary epithelial and breast carcinoma cells. The
      induction of apoptosis following loss of cell attachment to the extracellular
      matrix (anoikis) in untransformed mammary epithelial MCF10A cells was associated
      with significant downregulation of TLE1 expression. Forced expression of
      exogenous TLE1 in these cells promoted resistance to anoikis. In breast cancer
      cells, TLE1 expression was significantly upregulated following detachment from
      the extracellular matrix. Genetic manipulation of TLE1 expression via
      overexpression and downregulation approaches indicated that TLE1 promotes the
      anoikis resistance and anchorage-independent growth of breast carcinoma cells.
      Mechanistically, we show that TLE1 inhibits the Bit1 anoikis pathway by reducing
      the formation of the proapoptotic Bit1-AES complex in part through sequestration
      of AES in the nucleus. The mitochondrial release of Bit1 during anoikis as well
      as exogenous expression of the cytoplasmic localized Bit1 or its cell death
      domain induced cytoplasmic translocation and degradation of nuclear TLE1 protein.
      These findings indicate a novel role for TLE1 in the maintenance of anoikis
      resistance in breast cancer cells. This conclusion is supported by an
      immunohistochemical analysis of a breast cancer tissue array illustrating that
      TLE1 is selectively upregulated in invasive breast tumors relative to noninvasive
      ductal carcinoma in situ and normal mammary epithelial tissues.

PMID- 22952045
TI  - SINE retrotransposons cause epigenetic reprogramming of adjacent gene promoters.
AB  - Almost half of the human genome and as much as 40% of the mouse genome is
      composed of repetitive DNA sequences. The majority of these repeats are
      retrotransposons of the SINE and LINE families, and such repeats are generally
      repressed by epigenetic mechanisms. It has been proposed that these elements can
      act as methylation centers from which DNA methylation spreads into gene promoters
      in cancer. Contradictory to a methylation center function, we have found that
      retrotransposons are enriched near promoter CpG islands that stay methylation
      free in cancer. Clearly, it is important to determine which influence, if any,
      these repetitive elements have on nearby gene promoters. Using an in vitro
      system, we confirm here that SINE B1 elements can influence the activity of
      downstream gene promoters, with acquisition of DNA methylation and loss of
      activating histone marks, thus resulting in a repressed state. SINE sequences
      themselves did not immediately acquire DNA methylation but were marked by H3K9me2
      and H3K27me3. Moreover, our bisulfite sequencing data did not support that gain
      of DNA methylation in gene promoters occurred by methylation spreading from SINE
      B1 repeats. Genome-wide analysis of SINE repeats distribution showed that their
      enrichment is directly correlated with the presence of USF1, USF2, and CTCF
      binding, proteins with insulator function. In summary, our work supports the
      concept that SINE repeats interfere negatively with gene expression and that
      their presence near gene promoters is counter-selected, except when the promoter
      is protected by an insulator element.

PMID- 22952047
TI  - The degree of tumor volume reduction during the early phase of induction
      chemotherapy is an independent prognostic factor in patients with high-risk
      neuroblastoma.
AB  - BACKGROUND: In patients with high-risk neuroblastoma, the reduction in primary
      tumor volume was measured during the early phase of induction chemotherapy as an
      indicator of early tumor response, and the authors investigated whether the
      degree of tumor volume reduction could predict outcome in these patients.
      METHODS: Primary tumor volumes were measured both at diagnosis and at the first
      tumor response evaluation (after 2 or 3 cycles of induction chemotherapy) in 90
      patients with high-risk neuroblastoma who had volumetrically evaluable computed
      tomography or magnetic resonance scans. If the tumor volume at the first response
      evaluation was >40% of the initial tumor volume, then the patient was categorized
      as a poor responder; otherwise, the patient was categorized as a good responder.
      Outcomes were compared according to the degree of tumor volume reduction at the
      first response evaluation. RESULTS: The tumor volume reduction was greater in
      patients who remained relapse free than in patients who had a relapsed tumor
      (median percentage tumor volume, 21% vs 41.5%; P = .037). The 5-year relapse-free
      survival rate was higher in the good responders than in the poor responders (83%
      [95% confidence interval, 72%-94%] vs 51% [95% confidence interval, 31%-71%]; P =
      .002). In a multivariate analysis of relapse-free survival, a poor early response
      was identified as an independent, unfavorable prognostic factor (hazard ratio,
      4.24; 95% confidence interval, 1.59-11.29; P = .004). CONCLUSIONS: A greater
      reduction in tumor volume reduction the early phase of induction chemotherapy was
      associated with a better outcome in patients with high-risk neuroblastoma.
      Tailoring treatment intensity according to the early tumor response to induction
      chemotherapy may improve patient outcomes.

PMID- 22952048
TI  - Multivalency as a chemical organization and action principle.
AB  - Multivalent interactions can be applied universally for a targeted strengthening
      of an interaction between different interfaces or molecules. The binding partners
      form cooperative, multiple receptor-ligand interactions that are based on
      individually weak, noncovalent bonds and are thus generally reversible. Hence,
      multi- and polyvalent interactions play a decisive role in biological systems for
      recognition, adhesion, and signal processes. The scientific and practical
      realization of this principle will be demonstrated by the development of simple
      artificial and theoretical models, from natural systems to functional,
      application-oriented systems. In a systematic review of scaffold architectures,
      the underlying effects and control options will be demonstrated, and suggestions
      will be given for designing effective multivalent binding systems, as well as for
      polyvalent therapeutics.

PMID- 22952049
TI  - Cellular senescence occurring in the rabbit medial collateral ligament during
      healing.
AB  - Medial collateral ligament (MCL) healing proceeds in a temporally ordered fashion
      after injury. Despite the critical roles of fibroblasts during ligament repair,
      the phenotypic features of these healing fibroblasts have not been well
      characterized. Here, we show that healing MCL fibroblasts obtained from rabbits
      at 3-week postinjury exhibited higher rates of senescent phenotypes and produced
      higher levels of TGF-beta1, collagens, alpha-SMA, and matrix metalloproteinases
      (MMPs), than the corresponding fibroblasts from sham-operated MCLs. Mechanical
      stretch further enhanced the cellular senescence and the expression of TGF-beta1,
      collagens, alpha-SMA, and MMPs in both sham and healing MCL fibroblasts. In
      addition to MCL fibroblasts at 3-week postinjury, the increased cellular
      senescence was also detected in healing MCL fibroblasts obtained at 4- and 6-week
      postinjury. Most importantly, the association between the cellular senescence and
      ligament healing was confirmed in tissue sections by the senescence-associated
      beta-galactosidase (SA-beta-gal) staining. Using a recombinant TGF-beta1 and a
      neutralizing antibody, we found that those phenotypic changes, such as cellular
      senescence and the expression of collagens and MMPs, in MCL fibroblasts under
      mechanical loading conditions were regulated through TGF-beta1. Taken together,
      our results propose that cellular senescence and turnover of extracellular
      matrixes regulated by TGF-beta1 in MCL fibroblasts are critical for ligament
      healing.

PMID- 22952050
TI  - A versatile fluorescence approach to kinetic studies of hydrocarbon autoxidations
      and their inhibition by radical-trapping antioxidants.
AB  - We report a simple coumarin-triarylphosphine conjugate that undergoes
      fluorescence enhancement upon reaction with hydroperoxides and demonstrate its
      use to follow autoxidations of 7-dehydrocholesterol (at 37  degrees C) and
      hexadecane (at 160  degrees C) and their inhibition by antioxidants.

PMID- 22952051
TI  - Activation of innate anti-viral immune response genes in symptomatic benign
      prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is the most common urologic disease in men
      over age 50. Symptoms include acute urinary retention, urgency to urinate and
      nocturia. For patients with severe symptoms, surgical treatment is used to remove
      the affected tissue. Interestingly, the presence of histologic BPH does not
      always correlate with symptoms. The molecular basis of symptomatic BPH and how it
      differs from asymptomatic BPH is unknown. Investigation into the molecular
      players involved in symptomatic BPH will likely give insight into novel
      therapeutic, and potentially preventative, targets. We determined the expression
      of genes involved in the innate anti-viral immune response in tissues from
      patients undergoing surgery to alleviate the symptoms of BPH, and compared the
      results with prostate tissue with histologic BPH, but from patients with few
      urinary issues (asymptomatic BPH). We found that expression of complement factor
      I, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like protein 3G,
      oligoadenylate synthetase 2 and interferon-induced tetratricopeptide 1, four
      genes whose protein products are involved in the innate anti-viral immune
      response, was significantly transcriptionally upregulated in symptomatic BPH.
      Additionally, we observe hypomethylation and concomitant expression of ancient
      retroviral-like sequences, the long interspersed nuclear element 1
      retrotransposons, in symptomatic BPH when compared with normal prostate tissue.
      These findings merit further investigation into the anti-viral immune response in
      symptomatic BPH.

PMID- 22952053
TI  - Laponite blue: dissolving the insoluble.
AB  - The neutral organic dye indigo forms an inorganic-organic hybrid material with
      nanoclays (see picture; blue circles on disks symbolizing indigo, spheres
      indicating liberated cations) and can thus be transferred into aqueous solution.
      Solids recovered from these solutions resemble the ancient Maya Blue pigment. The
      method can also be applied to other hydrophobic species and may open the gate for
      novel solution chemistry, including photonic and catalytic applications.

PMID- 22952052
TI  - Heterogeneity of tibial plateau cartilage in response to a physiological
      compressive strain rate.
AB  - Knowledge of the extent to which tibial plateau cartilage displays non-uniform
      mechanical topography under physiologically relevant loading conditions is
      critical to evaluating the role of biomechanics in knee osteoarthritis. Cartilage
      explants from 21 tibial plateau sites of eight non-osteoarthritic female
      cadaveric knees (age: 41-54; BMI: 14-20) were tested in unconfined compression at
      100% strain/s. The elastic tangent modulus at 10% strain (E(10%) ) was calculated
      for each site and averaged over four geographic regions: not covered by meniscus
      (I); covered by meniscus-anterior (II); covered by meniscus-exterior (III); and
      covered by meniscus-posterior (IV). A repeated-measures mixed model analysis of
      variance was used to test for effects of plateau, region, and their interaction
      on E(10%) . Effect sizes were calculated for each region pair. E(10%) was
      significantly different (p<0.05) for all regional comparisons, except I-II and
      III-IV. The regional pattern of variation was consistent across individuals.
      Moderate to strong effect sizes were evident for regional comparisons other than
      I-II on the lateral side and III-IV on both sides. Healthy tibial cartilage
      exhibits significant mechanical heterogeneity that manifests in a common regional
      pattern across individuals. These findings provide a foundation for evaluating
      the biomechanical mechanisms of knee osteoarthritis.

PMID- 22952054
TI  - Dual-channel bipolar electrode focusing: simultaneous separation and enrichment
      of both anions and cations.
AB  - In this paper we show that a microelectrochemical cell comprising two parallel
      microchannels spanned by a single bipolar electrode can be used to simultaneously
      enrich and separate both anions and cations within a single microchannel. This is
      possible because reduction and oxidation of water at the cathodic and anodic
      poles of the bipolar electrode, respectively, lead to ion depletion zones.
      Specifically, TrisH(+) is neutralized by OH(-) at the cathodic pole, while
      acetate buffer is neutralized by H(+) at the anodic pole. This action creates a
      local electric field gradient having both positive and negative components, and
      hence positive and negative ions follow their respective field gradients leading
      to separation. In the presence of an opposing counter-flow (pressure driven flow
      in this case), enrichment also occurs. In addition to separation and enrichment
      in a single channel, it is also possible to simultaneously enrich cations in one
      microchannel and anions in the other. Enrichment is achieved by controlling
      experimental parameters, including the type of buffer and the direction and
      magnitude of the opposing counter-flow.

PMID- 22952055
TI  - A phaseguided passive batch microfluidic mixing chamber for isothermal
      amplification.
AB  - With a view to developing a rapid pathogen detection system utilizing isothermal
      nucleic acid amplification, the necessary micro-mixing step is innovatively
      implemented on a chip. Passive laminar flow mixing of two 6.5 MUl batches
      differing in viscosity is performed within a microfluidic chamber. This is
      achieved with a novel chip space-saving phaseguide design which allows, for the
      first time, the complete integration of a passive mixing structure into a target
      chamber. Sequential filling of batches prior to mixing is demonstrated.
      Simulation predicts a reduction of diffusive mixing time from hours down to one
      minute. A simple and low-cost fabrication method is used which combines dry film
      resist technology and direct wafer bonding. Finally, an isothermal nucleic acid
      detection assay is successfully implemented where fluorescence results are
      measured directly from the chip after a one minute mixing sequence. In
      combination with our previous work, this opens up the way towards a fully
      integrated pathogen detection system in a lab-on-a-chip format.

PMID- 22952056
TI  - Insulinlike growth factor (IGF)-1 administration ameliorates disease
      manifestations in a mouse model of spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by
      polyglutamine expansion in the androgen receptor. Patients develop slowly
      progressive proximal muscle weakness, muscle atrophy and fasciculations. Affected
      individuals often show gynecomastia, testicular atrophy and reduced fertility as
      a result of mild androgen insensitivity. No effective disease-modifying therapy
      is currently available for this disease. Our recent studies have demonstrated
      that insulinlike growth factor (IGF)-1 reduces the mutant androgen receptor
      toxicity through activation of Akt in vitro, and spinal and bulbar muscular
      atrophy transgenic mice that also overexpress a noncirculating muscle isoform of
      IGF-1 have a less severe phenotype. Here we sought to establish the efficacy of
      daily intraperitoneal injections of mecasermin rinfabate, recombinant human IGF-1
      and IGF-1 binding protein 3, in a transgenic mouse model expressing the mutant
      androgen receptor with an expanded 97 glutamine tract. The study was done in a
      controlled, randomized, blinded fashion, and, to reflect the clinical settings,
      the injections were started after the onset of disease manifestations. The
      treatment resulted in increased Akt phosphorylation and reduced mutant androgen
      receptor aggregation in muscle. In comparison to vehicle-treated controls, IGF-1
      treated transgenic mice showed improved motor performance, attenuated weight loss
      and increased survival. Our results suggest that peripheral tissue can be
      targeted to improve the spinal and bulbar muscular atrophy phenotype and indicate
      that IGF-1 warrants further investigation in clinical trials as a potential
      treatment for this disease.

PMID- 22952057
TI  - Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in
      humans.
AB  - Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has
      been implicated in the pathogenesis and/or severity of several lung diseases,
      including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar
      macrophages are the main resident leukocytes exposed to inhaled antigens. To
      obtain insight into which innate immune pathways become activated within human
      alveolar macrophages upon exposure to LPS in vivo, we conducted a study in eight
      healthy humans, in which we instilled sterile saline into a lung segment by
      bronchoscope, followed by instillation of LPS into the contralateral lung. Six
      hours later, a bilateral bronchoalveolar lavage was performed and whole-genome
      transcriptional profiling was done on purified alveolar macrophages, comparing
      cells exposed to saline or LPS from the same individuals. LPS induced
      differential expression of 2,932 genes in alveolar macrophages; 1,520 genes were
      upregulated, whereas 1,440 genes were downregulated. A total of 26 biological
      functions were overrepresented in LPS-exposed macrophages; 44 canonical pathways
      affected by LPS were identified, among which the genes associated with the role
      of pattern recognition receptors in recognition of bacteria and viruses
      represented the top pathway. Other pathways included cellular immune response,
      signaling by tumor necrosis factor (receptor) family members, cytokine signaling
      and glucocorticoid receptor signaling. These results reveal for the first time a
      large number of functional pathways influenced by the biologically relevant
      challenge provided by LPS administered into the airways. These data can assist in
      identifying novel targets for therapeutic intervention in pulmonary diseases
      associated with LPS exposure, including pneumonia, asthma and chronic obstructive
      pulmonary disease.

PMID- 22952058
TI  - CSE1L, a novel microvesicle membrane protein, mediates Ras-triggered microvesicle
      generation and metastasis of tumor cells.
AB  - Tumor-derived microvesicles are rich in metastasis-related proteases and play a
      role in the interactions between tumor cells and tumor microenvironment in tumor
      metastasis. Because shed microvesicles may remain in the extracellular
      environment around tumor cells, the microvesicle membrane protein may be the
      potential target for cancer therapy. Here we report that chromosome segregation 1
      like (CSE1L) protein is a microvesicle membrane protein and is a potential target
      for cancer therapy. v-H-Ras expression induced extracellular signal-regulated
      kinase (ERK)-dependent CSE1L phosphorylation and microvesicle biogenesis in
      various cancer cells. CSE1L overexpression also triggered microvesicle
      generation, and CSE1L knockdown diminished v-H-Ras-induced microvesicle
      generation, matrix metalloproteinase (MMP)-2 and MMP-9 secretion and metastasis
      of B16F10 melanoma cells. CSE1L was preferentially accumulated in microvesicles
      and was located in the microvesicle membrane. Furthermore, anti-CSE1L antibody
      conjugated quantum dots could target tumors in animal models. Our findings
      highlight a novel role of Ras-ERK signaling in tumor progression and suggest that
      CSE1L may be involved in the "early" and "late" metastasis of tumor cells in
      tumorigenesis. Furthermore, the novel microvesicle membrane protein, CSE1L, may
      have clinical utility in cancer diagnosis and targeted cancer therapy.

PMID- 22952061
TI  - A new wave of hormone research: crosstalk mechanisms.

PMID- 22952060
TI  - Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes
      the incidence and progression of advanced tumors in TRAMP mice.
AB  - Despite recent advances in understanding the biological basis of prostate cancer,
      management of the disease, especially in the phase resistant to androgen
      ablation, remains a significant challenge. The long latency and high incidence of
      prostate carcinogenesis provides the opportunity to intervene with
      chemoprevention to prevent or eradicate prostate malignancies. In this study, we
      have used human hormone-resistant prostate cancer cells, DU145 and PC3, as an in
      vitro model to assess the efficacy of xanthohumol (XN) against cell growth,
      motility and invasion. We observed that treatment of prostate cancer cells with
      low micromolar doses of XN inhibits proliferation and modulates focal adhesion
      kinase (FAK) and AKT phosphorylation leading to reduced cell migration and
      invasion. Oxidative stress by increased production of reactive oxygen species
      (ROS) was associated with these effects. Transgenic adenocarcinoma of the mouse
      prostate (TRAMP) transgenic mice were used as an in vivo model of prostate
      adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of
      age, induced a decrease in the average weight of the urogenital (UG) tract,
      delayed advanced tumor progression and inhibited the growth of poorly
      differentiated prostate carcinoma. The ability of XN to inhibit prostate cancer
      in vitro and in vivo suggests that XN may be a novel agent for the management of
      prostate cancer.

PMID- 22952059
TI  - Female mice are more susceptible to nonalcoholic fatty liver disease: sex
      specific regulation of the hepatic AMP-activated protein kinase-plasminogen
      activator inhibitor 1 cascade, but not the hepatic endotoxin response.
AB  - As significant differences between sexes were found in the susceptibility to
      alcoholic liver disease in human and animal models, it was the aim of the present
      study to investigate whether female mice also are more susceptible to the
      development of non-alcoholic fatty liver disease (NAFLD). Male and female
      C57BL/6J mice were fed either water or 30% fructose solution ad libitum for 16
      wks. Liver damage was evaluated by histological scoring. Portal endotoxin levels
      and markers of Kupffer cell activation and insulin resistance, plasminogen
      activator inhibitor 1 (PAI-1) and phosphorylated adenosine monophosphate
      activated protein kinase (pAMPK ) were measured in the liver. Adiponectin mRNA
      expression was determined in adipose tissue. Hepatic steatosis was almost similar
      between male and female mice; however, inflammation was markedly more pronounced
      in livers of female mice. Portal endotoxin levels, hepatic levels of myeloid
      differentiation primary response gene (88) (MyD88) protein and of 4
      hydroxynonenal protein adducts were elevated in animals with NAFLD regardless of
      sex. Expression of insulin receptor substrate 1 and 2 was decreased to a similar
      extent in livers of male and female mice with NAFLD. The less pronounced
      susceptibility to liver damage in male mice was associated with a superinduction
      of hepatic pAMPK in these mice whereas, in livers of female mice with NAFLD, PAI
      1 was markedly induced. Expression of adiponectin in visceral fat was
      significantly lower in female mice with NAFLD but unchanged in male mice compared
      with respective controls. In conclusion, our data suggest that the sex-specific
      differences in the susceptibility to NAFLD are associated with differences in the
      regulation of the adiponectin-AMPK-PAI-1 signaling cascade.

PMID- 22952063
TI  - Sexual assault in prepubertal girls: 'It is normal to be normal' - or is it?
      Evidence of vaginal penetration in prepubertal girls.
AB  - Study objective The purpose of this study is to evaluate the long-term effects of
      penile vaginal penetration in prepubertal girls. The specific emphasis is on
      whether there would be visible identifiable medical evidence of penetration on
      examinations done months or years after the event.  Literature review The medical
      literature regarding this subject was reviewed specifically for defendable
      evidence supporting a statement that there would be no findings as well as those
      that suggested that there would be visible evidence of trauma. Specific
      definitions of sexual assault, visible anatomic change from trauma, and sexual
      penetration are established for clarity. The effect of the lack of estrogen on
      the genital tissue of prepubertal girls is reviewed in relationship to the
      potential effects of trauma. The average diameters of the hymenal opening in this
      age group and the diameter of the erect male penis were reviewed.  Conclusion The
      result of the study both from review of the medical literature and an
      understanding of the anatomy and histology of the unestrogenized genitalia of the
      prepubertal girl makes it clear that if there has been forceful penile
      penetration of the hymen there will be both a history of pain and bleeding and
      healed evidence of this forceful penetration.

PMID- 22952062
TI  - Integrated experimental and model-based analysis reveals the spatial aspects of
      EGFR activation dynamics.
AB  - The epidermal growth factor receptor (EGFR) belongs to the ErbB family of
      receptor tyrosine kinases, and controls a diverse set of cellular responses
      relevant to development and tumorigenesis. ErbB activation is a complex process
      involving receptor-ligand binding, receptor dimerization, phosphorylation, and
      trafficking (internalization, recycling and degradation), which together dictate
      the spatio-temporal distribution of active receptors within the cell. The ability
      to predict this distribution, and elucidation of the factors regulating it, would
      help to establish a mechanistic link between ErbB expression levels and the
      cellular response. Towards this end, we constructed mathematical models to
      determine the contributions of receptor dimerization and phosphorylation to EGFR
      activation, and to examine the dependence of these processes on sub-cellular
      location. We collected experimental datasets for EGFR activation dynamics in
      human mammary epithelial cells, with the specific goal of model parameterization,
      and used the data to estimate parameters for several alternate models. Model
      based analysis indicated that: (1) signal termination via receptor
      dephosphorylation in late endosomes, prior to degradation, is an important
      component of the response, (2) less than 40% of the receptors in the cell are
      phosphorylated at any given time, even at saturating ligand doses, and (3)
      receptor phosphorylation kinetics at the cell surface and early endosomes are
      comparable. We validated the last finding by measuring the EGFR dephosphorylation
      rates at various times following ligand addition both in whole cells and in
      endosomes using ELISAs and fluorescent imaging. Overall, our results provide
      important information on how EGFR phosphorylation levels are regulated within
      cells. This study demonstrates that an iterative cycle of experiments and
      modeling can be used to gain mechanistic insight regarding complex cell signaling
      networks.

PMID- 22952064
TI  - Is there a sex difference in palm print ridge density?
AB  - BACKGROUND: Analysis of fingerprints and palm prints at the crime scene is vital
      to identify the suspect and establish a crime. Dermatoglyphics can even be
      valuable in identification of a dismembered hand during medicolegal
      investigations to establish the identity of an individual in cases of mass
      disasters/mass homicides. METHODS: The present research studies the variation in
      ridge density in different areas of the palm prints among men and women. The four
      prominent areas were analysed on the palm prints that included central prominent
      part of the thenar eminence (P1), hypothenar region; inner to the proximal axial
      triradius (P2), medial mount; proximal to the triradius of the second digit (P3)
      and lateral mount; proximal to the triradius of the fifth digit (P4). RESULTS:
      The mean palm print ridge density was significantly higher among women than men
      in all the designated areas in both hands except for the P3 area in the right
      hand. Statistically significant differences were observed in the palm print ridge
      density between the different palm areas in men and women in right and left
      hands. No significant right-left differences were observed in the palm print
      ridge density in any of the four areas of palm prints among men. In women, right
      left differences were observed only in the P3 and P4 areas of palm prints.
      CONCLUSIONS: This preliminary study indicates that though the palm print ridge
      density is a sexually dimorphic variable, its utility for estimation of sex in
      forensic identification may be limited owing to significant overlapping of
      values.

PMID- 22952065
TI  - Evaluation of alkylmaltosides as intestinal permeation enhancers: comparison
      between rat intestinal mucosal sheets and Caco-2 monolayers.
AB  - Alkylmaltosides are a class of non-ionic surfactant currently in clinical trials
      to improve nasal permeation of peptide drugs, however few studies have detailed
      their potential effects on intestinal permeation enhancement. Tetradecyl
      maltoside (TDM, C(14)), was examined in Caco-2 monolayers and in isolated rat
      jejunal and colonic mucosae mounted in Ussing chambers. Dodecyl maltoside (DDM,
      C(12)) was examined in mucosae. Parameters measured included critical micelle
      concentration (CMC), transepithelial electrical resistance (TEER), and apparent
      permeability coefficients (P(app)) of paracellular and transcellular flux
      markers. TDM and DDM decreased TEER and increased the P(app) of [(14)C]-mannitol
      and FD-4 across Caco-2 monolayers and colonic mucosae in the concentration range
      of 0.01-0.1% w/v, concentrations much higher than the CMC. Remarkably, neither
      agent had any effect on the TEER or fluxes of jejunal mucosae. Histopathology,
      cell death assays (MTT and LDH) and sub-lethal high content cytotoxicity analyses
      (HCA) were carried out with TDM. Exposure of colonic mucosae to high
      concentrations of TDM had no major effects on gross histology and ion transport
      function was retained. In Caco-2, HCA data at sub-lethal concentrations of TDM
      was consistent with the action of a mild non-ionic surfactant. In conclusion,
      alkylmaltosides are effective non-toxic permeation enhancers in isolated colonic
      tissue and their inclusion in oral peptide formulations directed to that
      intestinal region warrants further study.

PMID- 22952066
TI  - Lifting the field's "repression" of defenses.

PMID- 22952067
TI  - Addictive disorders: finding the predisposing traits.

PMID- 22952068
TI  - Bioenergetics for depression: something different for depression.

PMID- 22952069
TI  - Good news for dementia care: caregiver interventions reduce behavioral symptoms
      in people with dementia and family distress.

PMID- 22952070
TI  - Nuvoluccia in her lightdress: Lucia Joyce's mental illness in Finnegans Wake.

PMID- 22952071
TI  - Atypical antipsychotic use in patients with dementia: managing safety concerns.
AB  - Neuropsychiatric symptoms such as agitation and delusions occur commonly in
      elderly patients with dementia and often cause significant distress. Data on
      treatment efficacy are strongest for atypical antipsychotics, but these agents
      must be used with great caution. Adverse effects in patients with dementia
      include an increased risk of mortality and cerebrovascular events, as well as
      metabolic effects, extrapyramidal symptoms, falls, cognitive worsening, cardiac
      arrhythmia, and pneumonia. Conventional antipsychotics may pose an even greater
      safety risk. No clear efficacy evidence exists to support the use of alternative
      psychotropic classes (e.g., antidepressants, anticonvulsants), although they may
      be safer options. An antipsychotic trial is warranted when nonpharmacological
      intervention is unsuccessful and neuropsychiatric symptoms or associated
      behaviors cause severe distress or pose a significant safety risk. Before an
      atypical antipsychotic is started, a comprehensive assessment should be performed
      to rule out medical causes of the neuropsychiatric symptoms and to ascertain
      whether any contributing environmental or caregiver factors are present. Risks,
      benefits, and alternatives should be discussed with the patient and surrogate
      decision maker, with an opportunity given to ask questions. Dosages should be the
      lowest necessary, and metabolic parameters should be regularly monitored. Face-to
      face visits are important to monitor response, tolerance, and the need for
      continued treatment. For patients in whom neuropsychiatric symptoms have been
      much improved or have been in remission for 3-6 months, a discontinuation trial
      should be considered. Through careful selection of appropriate patients for
      treatment, education of patients and caregivers, and close monitoring, safety
      risks can be minimized.

PMID- 22952073
TI  - Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms
      of dementia.
AB  - OBJECTIVE: Behavioral and psychological symptoms are common in dementia, and they
      are especially stressful for family caregivers. Nonpharmacological (or
      psychosocial) interventions have been shown to be effective in managing
      behavioral and psychological symptoms, but mainly in institutional settings. The
      authors reviewed the effectiveness of community-based nonpharmacological
      interventions delivered through family caregivers. METHOD: Of 1,665 articles
      identified in a literature search, 23 included unique randomized or
      pseudorandomized nonpharmacological interventions with family caregivers and
      outcomes related to the frequency or severity of behavioral and psychological
      symptoms of dementia, caregiver reactions to these symptoms, or caregiver
      distress attributed to these symptoms. Studies were rated according to an
      evidence hierarchy for intervention research. RESULTS: Nonpharmacological
      interventions were effective in reducing behavioral and psychological symptoms,
      with an overall effect size of 0.34 (95% CI=0.20-0.48; z=4.87; p<0.01), as well
      as in ameliorating caregiver reactions to these behaviors, with an overall effect
      size of 0.15 (95% CI=0.04-0.26; z=2.76; p=0.006). CONCLUSIONS: Nonpharmacological
      interventions delivered by family caregivers have the potential to reduce the
      frequency and severity of behavioral and psychological symptoms of dementia, with
      effect sizes at least equaling those of pharmacotherapy, as well as to reduce
      caregivers' adverse reactions. The successful interventions identified included
      approximately nine to 12 sessions tailored to the needs of the person with
      dementia and the caregiver and were delivered individually in the home using
      multiple components over 3-6 months with periodic follow-up.

PMID- 22952072
TI  - Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes
      for drug dependence.
AB  - OBJECTIVE: Not everyone who takes drugs becomes addicted, but the likelihood of
      developing drug addiction is greater in people with a family history of drug or
      alcohol dependence. Relatively little is known about how genetic risk mediates
      the development of drug dependence. By comparing the phenotypic profile of
      individuals with and without a family history of addiction, the authors sought to
      clarify the extent to which cognitive dysfunction and personality traits are
      shared by family members--and therefore likely to have predated drug dependence-
      and which aspects are specific to drug-dependent individuals. METHOD: The authors
      assessed cognitive function and personality traits associated with drug
      dependence in stimulant-dependent individuals (N=50), their biological siblings
      without a history of drug dependence (N=50), and unrelated healthy volunteers
      (N=50). RESULTS: Cognitive function was significantly impaired in the stimulant
      dependent individuals across a range of domains. Deficits in executive function
      and response control were identified in both the stimulant-dependent individuals
      and in their non-drug-dependent siblings. Drug-dependent individuals and their
      siblings also exhibited elevated anxious-impulsive personality traits relative to
      healthy comparison volunteers. CONCLUSIONS: Deficits in executive function and
      response regulation as well as anxious-impulsive personality traits may represent
      endophenotypes associated with the risk of developing cocaine or amphetamine
      dependence. The identification of addiction endophenotypes may be useful in
      facilitating the rational development of therapeutic and preventive strategies.

PMID- 22952074
TI  - Effect of Alzheimer's disease risk genes on trajectories of cognitive function in
      the Cardiovascular Health Study.
AB  - OBJECTIVE: The trajectory of cognitive decline in patients with late-onset
      Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are
      associated with Alzheimer's disease, but it is unknown whether they exert their
      effects by altering cognitive trajectory in elderly individuals at risk for the
      disease. METHOD: The authors developed a Bayesian model to fit cognitive
      trajectories in a cohort of elderly subjects and test for genetic effects. They
      first validated the model's ability to detect the previously established effects
      of APOE epsilon4 alleles on age at cognitive decline and of psychosis on the rate
      of cognitive decline in 802 subjects from the Cardiovascular Health Cognition
      Study who did not have dementia at study entry and developed incident dementia
      during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1
      on age and rate of decline in 1,831 subjects who did not have dementia at study
      entry and then did or did not develop incident dementia by study's end. RESULTS:
      The model generated robust fits to the observed cognitive trajectory data, and
      validation analysis supported the model's utility. CLU and CR1 were associated
      with more rapid cognitive decline. PICALM was associated with an earlier age at
      midpoint of cognitive decline. Associations remained after accounting for the
      effects of APOE and demographic factors. CONCLUSIONS: Evaluation of cognitive
      trajectories provides a powerful approach to dissecting genetic effects on the
      processes leading to cognitive deterioration and Alzheimer's disease.

PMID- 22952075
TI  - Short-term tropisetron treatment and cognitive and P50 auditory gating deficits
      in schizophrenia.
AB  - OBJECTIVE: The alpha7 nicotinic acetylcholine receptor (nAChR) is associated with
      cognitive and P50 auditory gating deficits in schizophrenia, and alpha7 nAChR
      agonists can potentially reverse these deficits. The authors examined multiple
      dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on
      cognition and P50 deficits in schizophrenia. METHOD: In a randomized double-blind
      design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than
      0.5 and were stabilized on 3-6 mg/day of risperidone were randomly assigned to
      receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10),
      or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered
      the Chinese-language version of the Repeatable Battery for the Assessment of
      Neuropsychological Status at baseline and after 10 days of treatment. RESULTS:
      After 10 days of treatment, all three daily doses of tropisetron significantly
      improved overall cognitive deficits, with 10 mg showing the greatest improvement
      for the immediate memory index score and 20 mg for the delayed memory index score
      on the cognitive battery. The P50 deficits were also improved, and that
      improvement was significantly correlated with cognitive improvement. Two patients
      in the 20 mg/day group dropped out because of adverse effects, but the other
      dosages were well tolerated. CONCLUSIONS: The improvement of cognition with
      tropisetron appeared to be associated with normalization in P50 deficits. Thus,
      alpha7 nAChR agonists appear to be a promising therapeutic approach for the
      treatment of cognitive deficits that are related to abnormal P50 suppression in
      schizophrenia.

PMID- 22952076
TI  - Studies in humans and mice implicate neurocan in the etiology of mania.
AB  - OBJECTIVE: Genome-wide association has been reported between the NCAN gene and
      bipolar disorder. The aims of this study were to characterize the clinical
      symptomatology most strongly influenced by NCAN and to explore the behavioral
      phenotype of Ncan knockout (Ncan(-/-)) mice. METHOD: Genotype/phenotype
      correlations were investigated in patients with bipolar disorder (N=641) and the
      genetically related disorders major depression (N=597) and schizophrenia (N=480).
      Principal components and genotype association analyses were used to derive main
      clinical factors from 69 lifetime symptoms and to determine which of these
      factors were associated with the NCAN risk allele. These analyses were then
      repeated using the associated factor(s) only in order to identify the more
      specific clinical subdimensions that drive the association. Ncan(-/-) mice were
      tested using diverse paradigms, assessing a range of behavioral traits, including
      paradigms corresponding to bipolar symptoms in humans. RESULTS: In the combined
      patient sample, the NCAN risk allele was significantly associated with the
      "mania" factor, in particular the subdimension "overactivity." Ncan(-/-) mice
      were hyperactive and showed more frequent risk-taking and repetitive behaviors,
      less depression-like conduct, impaired prepulse inhibition, amphetamine
      hypersensitivity, and increased saccharin preference. These aberrant behavioral
      responses normalized after the administration of lithium. CONCLUSIONS: NCAN
      preferentially affected mania symptoms in humans. Ncan(-/-) mice showed
      behavioral abnormalities that were strikingly similar to those of the human mania
      phenotype and may thus serve as a valid mouse model.

PMID- 22952077
TI  - Protecting psychiatrists' reputations on the Internet.

PMID- 22952079
TI  - Celiac disease and schizophrenia.

PMID- 22952080
TI  - Alternative interpretation for the early detection of psychosis study.

PMID- 22952082
TI  - Bilateral pallidal necrosis and cardiac toxicity in a patient with venlafaxine
      and bupropion overdose.

PMID- 22952089
TI  - Recovery of ionic liquids with aqueous two-phase systems induced by carbon
      dioxide.
AB  - Recovery is a very important factor for the industrial application of ionic
      liquids (ILs). In this work, a novel method is presented for the recovery of ILs
      by using carbon dioxide (CO2-induced formation of aqueous two-phase systems
      (ATPSs). It was found that, in the presence of amines, introduction of CO2 into
      aqueous IL solutions leads to the formation of ATPSs at 25  degrees C and
      atmospheric pressure, in which the upper phase is ammonium-salt-rich and the
      lower phase is IL-rich. Thus, the ILs in aqueous solutions can be significantly
      enriched, and the amines can be regenerated by heating and bubbling Ar or N2 in
      the salt-rich phase. To better understand the recovery of ILs, the phase diagrams
      of the ATPSs were measured at 25  degrees C, and the effects of the molecular
      structure of the ILs and the amines and temperature of the systems on the
      recovery efficiency of the ILs were investigated. It was shown that the single
      step recovery efficiency of the ILs could be as high as 99 % in the presence of
      primary or secondary amines. Therefore, this new method could potentially be
      sustainable, efficient, and attractive to industry.

PMID- 22952090
TI  - Patient level decision making in recurrent acute rhinosinusitis: a cost-benefit
      threshold for surgery.
AB  - OBJECTIVES/HYPOTHESIS: A previous effort to identify the threshold for surgery in
      recurrent acute rhinosinsutis (RARS) was made based on workforce productivity.
      While this macroeconomic approach is useful for population-level decision making,
      patient-level decision making is variable and driven by personal and financial
      implications. This microeconomic study seeks to identify threshold levels of
      infection where surgery becomes worthwhile to patients based on costs, lost
      income, and quality of life. STUDY DESIGN: Cost-Benefit Breakeven Analysis.
      METHODS: A breakeven analysis was constructed from literature reported medical
      and surgical response rates, change in quality of life as a result of
      intervention, and costs to patients. RESULTS: A breakeven threshold occurs when
      patients suffer from 1.3-2.8 episodes per year under the conservative assumption
      that the effects of surgery do not extend beyond 19 months--the longest outcomes
      reported. DISCUSSION: Due to possible confusion with URTIs, we have adopted an
      approach similar to that advocated by the Rhinosinusitis Task Force. Given the
      average number of URTIs suffered by adults annually is 1.4-2.3. We suggest adding
      this to the threshold number of episodes calculated in the present model. Under
      the most conservative assumptions, this suggests that patients should consider
      surgery when suffering from five or more episodes per year.

PMID- 22952091
TI  - Health is wealth: considerations to European healthcare.

PMID- 22952092
TI  - Morphology of renal interstitial fibroblasts.
AB  - INTRODUCTION: Renal fibrogenesis is a process common to all progressive kidney
      diseases. The main executive cell in this process is the fibroblast, by secreting
      and remodelling the extracellular matrix. The number of fibroblasts is minor in a
      healthy kidney interstitium, but it increases during the process of fibrosis.
      Their morphology and immunophenotype vary due to different intrinsic and
      extrinsic factors which makes their identification and visualization, as well as
      determination of their origin, very difficult. MATERIAL AND METHODS: We performed
      morphological and immunohistochemical analyses on kidney biopsies with
      interstitial fibrosis, using the following antibodies: Vimentin, alpha-SMA,
      S100A4, Cadherin 9 and CD34. We also did light-microscopy analyses of semithin
      sections of tissue embedded in epoxy resin and stained with Toluidine blue.
      RESULTS: Our observations show that different cells in the fibroblastic
      population show positivity for different markers, thus contributing to the theory
      that there are different subpopulations of fibroblasts, with different origins,
      that take part in renal fibrogenesis.

PMID- 22952093
TI  - Proteomic biomarkers for the early detection of acute kidney injury.
AB  - Acute kidney injury (AKI) comprises several syndromes that are associated with a
      sudden decrease in renal function. AKI is a common condition especially among
      critically ill patients. It is typically multifactorial and of great prognostic
      significance. The incidence of AKI has increased while the associated mortality
      rate has remained unchanged over the last years. Recent definitions of AKI,
      namely the Risk, Injury, Failure, Loss of renal function and End-stage kidney
      disease (RIFLE) classifycation or the Acute Kidney Injury Network (AKIN)
      criteria, incorporate serum creatinine and urine output as the principal markers
      to define and detect AKI. However, elevated serum creatinine or oliguria were
      demonstrated to detect AKI at late stages of renal injury when preventive
      strategies may be less effective. Therefore, there has recently been a great
      scientific interest in obtainng valuable markers for early AKI detection. In the
      last 5 years numerous new markers such as neutrophil-gelatinase associated lipo
      calin, interleukin-18, cystatin C and kidney injury molecule 1 in the urine
      and/or serum have been studied and proposed as early detection markers of AKI.
      Persistently, these markers performed well in initial pilot trials. However,
      these promising results could often not be confirmed in later, larger multicentre
      trials and limitation of these biomarkers in the early diagnosis of renal injury
      were discovered. Furthermore, as AKI is multi-factorial and heterogeneous in
      origin, it seems likely that not one single marker but a panel of biomarkers will
      be required to detect all subtypes of AKI early during their evolution. This has
      initiated proteomic studies to develop panels of biomarkers which may facilitate
      early detection of AKI. The present review will focus on the most important
      clinical studies evaluating the ability of single AKI biomarkers and on those in
      clinical proteomics that attempted to establish panels of biomarkers in urine for
      early and accurate AKI diagnosis and prognosis.

PMID- 22952094
TI  - Choledochal cysts: diagnosis and treatment.
AB  - The aim of this study is to show the different diagnostic procedures and
      treatment in patients diagnosed with congenital choledochal cysts. Choledochal
      cysts are congenital anomalies of the bile ducts and include cystic dilatation of
      the extrahepatic and intrahepatic biliary ducts or both. The study shows ten
      patients diagnosed as having choledochal cysts. Diagnosis was established by
      clinical and radiographic findings including: ultrasound (US), magnetic resonance
      cholangiopancreatograpy (MRCP), endoscopic retrograde cholangiopancreatography
      (ERCP), percutaneous transhepatic cholangiography (PTC) and cytological
      examination of the bile juice. In the study choledochal cysts were classified
      according to the Todani classification. Most common cysts were type I (six
      cases); type III (one case), type IVa (one case) and two patients were type V
      cysts (Caroli disease). The most frequent symptoms were abdominal pain, jaundice
      and cholangitis. US findings were sensitive for the preliminary diagnosis of
      choledochal cysts in all the patients. MRCP accurately defined the cyst anatomy
      and the site of the biliary origin in all the cases with extrahepatic cysts. In
      three cases ERCP clearly demonstrated the cyst and by PTC smaller cysts were well
      defined. Cytological examination of the bile juice obtained during the PTC
      procedure showed malignant cells in one case. Therefore pancreaticoduodenectomy
      was performed and pathological examination showed associated cholangiocarcinoma.
      Five years after the operation the patient was well and free of the disease. Five
      patients underwent surgical treatment with a total cyst excision and Roux-en-Y
      hepaticojejunostomy while the surgical approach in two patients was partial cyst
      excision and cystojejunostomy. Patients with Caroli disease were conservatively
      treated and 3 with interventional endoscopic procedures. Despite US evidence
      suggesting choledochal cyst diagnosis, other supportive radiographic imaging
      modalities such as MRCP, ERCP and PTC are required to define the precise cyst
      anatomy and are essential for the preoperative assessment. Total cyst excision is
      recommended for reducing cyst-related complications and risk of
      cholangiocarcinoma.

PMID- 22952095
TI  - Peripheral arterial disease and diabetes.
AB  - There are two points of view for the interplay of peripheral arterial disease
      (PAD) with diabetes: the higher prevalence of PAD that is presented in diabetes
      than in the general population, and secondly that peripheral atherosclerosis is a
      marker of polyvascular disease in these pts. The main aim of this review is to
      describe risk factors, diagnostic approaches and treatment modalities of this
      condition.

PMID- 22952096
TI  - Biopsy of the transplanted kidney--role of protocol biopsies.
AB  - Traditionally, renal allograft biopsies were performed mainly in the setting of
      acute graft dysfunction. Recently, there has been a change of paradigms. Several
      reports suggested that acute rejection of the graft and chronic allograft
      nephropathy are often subclinical without any deterioration in the graft
      function. This raises the issue of biopsies in functionally stable allografts
      (e.g. protocol biopsies) and the clinically useful information they provide.
      Namely, recent reports provide evidence in favour of treating biopsy-proven
      subclinical rejections. Moreover, by early identification of chronic histological
      lesions, protocol biopsies give an opportunity for individualized
      immunosuppressive regimen and use of targeted therapeutic strategies, in order to
      prevent chronic allograft dysfunction and improve long-term graft outcome. In
      this review, diagnostic, therapeutic and research benefit information on protocol
      biopsies performed in stable kidney recipients are described.

PMID- 22952097
TI  - Minimal screening analysis based algorithm for diagnosis and clinical
      stratification of patients with acute myeloid leukaemia (AML):  single centre
      experience.
AB  - In this paper we present our results from a study designed in order to establish
      and standardize a diagnostic algorithm for acute myeloid leukaemia (AML) in the
      Republic of Macedonia. A total of 146 consecutive adult patients (>15 years) were
      enrolled in the study. First, we determined the correct lineage assignment of the
      blast cells and evaluated the incidence of the favourable PML/RARalpha, AML1/ETO,
      CBFbeta/MYH11 genetic markers among the AML cases. Additionally, the obtained
      results were correlated with patients' age, comorbidities, and performance
      status, and each single AML patient was stratified to effective treatment
      strategy. Our results showed that morphology and cytochemistry established a
      lineage in 132 (89.1%) of the patients, but not in 16 cases that presented as
      acute leukaemia, of which 7 were assigned as myeloid, and in two a non
      haematopoietic malignancy was indicated with immunophenotyping. Mulitparameter
      flow cytometry immunophenotyping also changed the assigned lineage based on
      morphology and cytochemistry in 5 (3.3%) of the patients from lymphoid to myeloid
      and improved diagnosis in 21 (14.1%) cases. By using a reverse transcriptase
      polymerase chain reaction (RT-PCR) essay 28 (23.1%) patients were classified in
      the prognostically favourable AML genetic group; 8 patients expressed the fusion
      transcript PML/RARalpha AML1/ETO and 15 CBFbeta/MYH11. Moreover, analyses of the
      age, performance status and comorbidities further strtified an additional 12.5%
      of the patients to a different risk-adapted therapy. The applied minimal
      screening-analysis-based diagnostic algorithm enabled improved and more precise
      diagnosis and clinical stratification in 37.2 % of AML patients from our study
      group.

PMID- 22952098
TI  - Assesment of non-relapse mortality (NRM) and long-term survival after autologous
      stem cell transplantation (ASCT) in patients with lymphoproliferative diseases.
AB  - A balanced risk-benefit approach to haematopoietic stem cell transplantation
      (HSCT) is the key for maximized chances of cure with acceptable quality of life
      for patients with advanced haematological malignancies. The aim was to try to
      assess the prognostic value of comorbidity and other independent variables
      concerning pretransplant mobilization strategies that affect auto SCT in patients
      with lymphoproliferative diseases.We stratified outcomes among 90 consecutive
      adult autologous recipients with lymphoproliferative diseases. 55% of patients
      were classified in the low index group for haematopoietic stem cell
      transplantation with comorbidity index (HCT-CI) scores between 0-1, 27% of
      patients with lymphoproliferative diseases had intermediate HCT-CI scores 1-2 and
      12% of patients were in high HCT-CI group with a score>=3 and 6% undetermined.
      Two year NRM was 36% (95% CI: 17-36%), 26% (95% CI 15-39%) and 30% (95% CI: 22
      39%) in the low, intermediate and high-risk HCT-CI groups respectively. The HCT
      CI has been shown to sensitively capture organ comorbidities and provide valuable
      prognostic information for assignments of patients to clinical trials. Still,
      many questions remain to be answered, auch as good sample size, equal
      stratification of patients into risk groups, and also implementing better
      pretransplant assessment.

PMID- 22952099
TI  - Immune thrombocytopenic purpura in adults in the last 10 years: single-centre
      experience.
AB  - BACKGROUND: Immune thrombocytopenic purpura (ITP) is a benign disease with low
      morbidity and mortality and frequent remissions that occur spontaneously or in
      response to first-line treatment with steroids or splenectomy. AIM: The purpose
      of this study is to describe the clinical outcomes of 170 patients with ITP
      diagnosed and/or treated in our hospital between 2000 and 2010. METHODS AND
      RESULTS: The median age at diagnosis was 47 years. Forty three (25%) were
      asymptomatic, 65% had minor skin or mucosal bleeding and 10% had significant
      bleeding from the gastrointestinal or genitourinary system. The median platelet
      count at diagnosis was 13x10(9)/L (range: 0-98x10(9)/L). Median follow-up of all
      patients was 13 months. Ninety-five patients had a follow-up longer than 12
      months, with median 44 months (range 14-384). Corticosteroids were the initial
      treatment for 161/170 (95%) patients, 38 (22%) were splenectomized, 25 (14.7%)
      were treated with intravenous gamma globulins, while 9 did not received any
      specific treatment. A complete response to initial treatment (prednisone+/
      splenectomy) was achieved in 55/161 (34.2%), a partial response in 90 (55.9%) and
      no response in 16 (9.9%) patients. In the group of patients with follow-up longer
      than 1 year; 28 (29%) patients had refractory or unresponsive ITP with a median
      follow-up of 66 months. All patients with refractory ITP were treated with
      steroids, 11 were splenctomized, significantly more patients with refractory ITP
      12 (43%) were treated with IVIG compared with other ITP patients (16%), p=0.005.
      The median age of 38 splenectomized patients was 28 years and it is significantly
      different from the other patients (p<0.001). There were no significant
      differences in other characteristics between splenctomized or refractory ITP and
      other patients at diagnosis. CONCLUSION: Our results were similar to results
      already reported in other similar studies.

PMID- 22952100
TI  - Association of polymorphisms in human platelet antigens with idiopathic
      thrombocytopenic  purpura in Macedonians.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized
      by thrombocytopenia due to the presence of platelet autoantibodies specific for
      platelet membrane glycoproteins, such as GPIIb/IIIa, GPIb/IX and GPIa/IIa. These
      autoantibodies cause an accelerated clearance of opsonized platelets by
      phagocytes and inhibition of platelet production. Human platelet antigen (HPA)
      systems HPA-1, HPA-2, HPA-3 and HPA-5 are components of platelet GP complexes
      GPIIb/IIIa, GPIb/IX and GPIa/IIa. The HPA system consists of more than 12 bi
      allelic antigen polymorphisms in which a base-pair substitution leads to change
      in an amino acid sequence of a membrane glycoprotein expressed on the platelet
      surface. The aim of this study was to examine the association of HPA-1, HPA-2,
      HPA-3 and HPA-5 polymorphisms with idiopathic thrombocytopenic purpura. We
      performed genotyping of HPA-1, HPA-2, HPA-3, and HPA-5 systems in 60 patients
      with ITP and 120 healthy participants. Genotyping of HPA-1, -2, -3, and -5
      alleles were performed by PCR and RFLP methods by using specific primers and
      restriction enzymes. Allele and genotype frequencies of HPA-1, HPA-3, and HPA-5
      were not significantly different between patients and healthy participants. After
      Bonferroni adjustment a significant association in ITP patients with HPA-2
      alleles (P=0.015, OR=1.923, CI=1.126-3.284) was found. Allele frequencies for HPA
      2a were 0.852 in healthy participants and 0.750 in patients, and for HPA-2b 0.148
      and 0.250 respectively. These results suggests that HPA-2b allele was more
      frequent in patients with ITP and may be involved in the formation of a specific
      autoepitope.

PMID- 22952101
TI  - Predicting outcome after severe brain injury in risk neonates using the serum
      S100B biomarker: results using single (24 h) time-point.
AB  - BACKGROUND AND OBJECTIVES: In recent years, biochemical markers have been
      employed to predict the outcome of risk neonates with severe asphyxia
      contributing to traumatic brain injury (TBI). In mild TBI S100B has shown the
      most promise as a marker of outcome. The objectives of this study were: (i) to
      show the range of serum S100B levels during the acute phase after asphyxia in
      neonates and premature newborns, (ii) to determine if S100B has potential to
      discriminate favourable from unfavourable outcomes in neonates and premature
      newborns with similar severity of brain injury and (iii) to establish an S100B
      'cut-off' point for lethal outcome. METHODS: 119 neonates were recruited, divided
      into an overall risk group (N=71) and control group (N=48). The risk neonates
      were categorized into subgroups according to their clinical presentation. A serum
      blood sample was obtained from each patient at a 24 h post-injury time-point.
      S100B levels were measured using the ECLIA (Electro-Chemi-Luminiscence Immuno
      Assay) method. Injuries were coded using an internationally recognised injury
      severity scoring system (ISS). RESULTS: S100B levels were significantly higher in
      asphyxiated term neonates (N=29; M=0.64) than in premature neonates (N=30;
      M=0.18) and IUGR (intrauterine growth retardation) neonates (N=9; M=0.03). The
      neonates with a neurological defect (N=3; M=1.73) measured the highest level of
      S100B. The average serum S100B levels for the control group (N=48) was 0.12 ugL(
      1); cut-off point. CONCLUSION: During the first 24 h of life S100B protein in
      term neonates was significantly higher compared to all the other groups (cut-off
      was 0.12 ugL), except the neonates with neurological defects. S100B protein is a
      good indicator of brain damage in term neonates, especially in the first 24 h of
      life.

PMID- 22952102
TI  - Oral habits among pre-elementary children in Bitola.
AB  - AIM: The purpose of this study was to determine the prevalence of oral habits
      (nail biting, finger sucking) among the pre-elementary children in Bitola.
      METHODS: In the observational average, (cross-sectional) study were covered 890
      children 3 and 5 years old, who came to regular medical checkups during the
      period from January to December 2009, in the Health Centre in Bitola. During the
      research the following methods were applied: psychological testing (Chuturik
      Test), clinical paediatric examination, interview with the parents and applying
      the Questionnaire on Children's Behaviour, Child Behaviour Checklist-Achenbach,
      1981, in Hill R., and Castrol E. (2002): Getting rid of Ritalin, Hampton Roads
      Publishing Company, Inc. RESULTS: The research included 890 children, of whom 401
      were three yeas old and 489 five years old, and 51.6% male and 48.4% female. The
      prevalence of oral habits among the subjects was 35.39%. Statistical analyses
      showed that these habits can be found (p<0.05) among 3-year-old children, but the
      tested difference concerning the gender was statistically insignificant (p>0.05).
      Children who live in a rural environment, who do not have their own room and do
      not use a computer, statistically significantly manifested oral habits more often
      (p<0.05). Tested differences in the frequency of oral habits according to the
      number of family members were statistically insignificant (p>0.05). Children
      whose parents have primary education and whose mothers are working and have
      minimal incomes manifested a significantly more frequent presence of oral habits
      for the level of p<0.01 and p<0.05. CONCLUSION: These oral habits have a
      prevalence of 35.39% among the pre-elementary children in Bitola and should be
      viewed as a major public health problem. Because of their influence on the
      development of the orofacial system, the responsibility primarily of paediatrist
      and children's dentists is great for their prevention, early diagnosis and
      treatment in collaboration with other specialists, the child and parents.

PMID- 22952103
TI  - The influence of remifentanil and remifentanil-plus-sevoflurane-controlled
      hypotension on mean arterial pressure and heart rate in children.
AB  - The aim of the study is to determine the influence of remifentanil and
      remifentanil-plus-sevoflurane-induced anaesthesia on mean arterial pressure and
      heart-rate during controlled hypotension in children and to evaluate the quality
      of the operative field. METHODS: 30 children, ASA I physical status were
      scheduled for middle ear microsurgery for cochlear implantation and divided into
      2 groups: R group (15 children who received remifentanil as a hypotensive agent
      during general anaesthesia). R + S group (15 children who received remifentanil
      and sevoflurane as hypo-tensive agents together to reach the hypotensive level
      during general anaesthesia). The hypotensive level was defined as 20% decrease of
      baseline MAP. We used oral medication for sedation (1 mg/kg Flormidal), 10 mg/kg
      parace-tamol rectally for postoperative analgesia. Two variables were measured
      during the anaaesthesia: MAP and HR at five time intervals. We also measured the
      duration of hypotension, the time to reach a hypotensive level and the duration
      of anaesthesia and surgery (inmins). The quality of the surgical field in terms
      of dryness was rated every ten minutes by the surgeon who used a six-point scale,
      0-5 scale (0=no bleeding, visually bloodless field; 5=uncontrolled bleeding).
      RESULTS: Demographic analyses showed that 13 of the patients were female, 17 of
      them were male, with an age-range of 4.75+/-3.2 years in the R group of patients
      and 3.5+/-4.1 in the R+S group of patients. Duration of hypotension was 135+/-4
      minutes (R) and 120+/-3 minutes (R+S). Duration of anaesthesia was 160+/-10
      minutes (R) and 140+/-9 minutes (R+S). The duration of surgery was 150+/-5
      minutes (R) and 130+/-4 minutes (R+S). The time to reach hypotensive level was
      shorter in R+S group (5+/-1 minutes) than R group (7+/-6 minutes). There was no
      statistically significant difference in MAP values measured at T1, T2, T3 and T4
      time intervals between the two groups of patients (R and R+S group). We achieved
      hypotensive anaesthesia levels of MAP in both group of patients. The influence of
      anesthesia on HR was analysed at the same time intervals. In T2 time interval (30
      minutes after the induction of anaesthesia), HR values in R group patients were
      statistically significantly higher than referent hypotensive values in the R+S
      group of patients (70-80 bpm). We could see the same result of HR values at T3
      and T4 time intervals (90 and 120 minutes after the induction) in R group
      patients compared with HR values in the R+S group. We achieved a hypotensive
      level of HR (70-80 bpm) only at R+S group of patients, which means that
      remifentanil in combination with sevoflurane is an excellent combination for
      maintaining hypotension during general anaesthesia. The lowest hypotensive level
      of HR was measured 120 minutes after the induction of anaesthesia in the R+S
      group of patients (69 bpm). Remifentanil and remifentanil in combination with
      sevoflurane are effective in inducing consistent and sustained controlled
      hypotension in children undergoing middle ear microsurgery.

PMID- 22952104
TI  - Fungal rhinosinusitis.
AB  - Fungi are a major part of the ecosystem. In fact, over 250 fungal species have
      been reported to produce human infections. More than ever, fungal diseases have
      emerged as major challenges for physicians and clinical microbiologists. The aim
      of this study was to summarize the diagnostic procedures and endoscopic surgical
      treatment of patients with fungal rhinosinusitis. Eleven patients, i.e. 10% of
      all cases with chronic inflammation of paranasal sinuses, were diagnosed with
      fungal rhinosinusitis. Ten of them were patients with a noninvasive form, fungus
      ball, while only one patient was classified in the group of chronic invasive
      fungal rhinosinusitis which was accompanied with diabetes mellitus. All patients
      underwent nasal endoscopic examination, skin allergy test and had preoperative
      computed tomography (CT) scans of the sinuses in axial and coronal plane.
      Functional endoscopic sinus surgery was performed in 10 patients with fungus
      ball, while a combined approach, endoscopic and external, was done in the
      immunocompromised patient with the chronic invasive form of fungal
      rhinosinusitis. Most cases (9/11) had unilateral infection. In 9 cases infection
      was restricted to a single sinus, and here the maxillary sinus was most commonly
      affected (8/9) with infections in other patients being restricted to the sphenoid
      sinus (1/9). Two patients had infections affecting two or more sinuses. In
      patients with an invasive form of the fungal disease there was involvement of the
      periorbital and orbital tissues. In patients with fungus ball the mycelia masses
      were completely removed from the sinus cavities. Long-term outcome was positive
      in all the operated patients and no recurrence was detected. The most frequent
      fungal agent that caused rhinosinusitis was Aspergillus. Mucor was identified in
      the patient with the invasive form. Endoscopic examination of the nasal cavity
      and CT scanning of paranasal sinuses followed by endoscopic sinus surgery were
      represented as valuable diagnostic and therapeutic procedures for fungal
      rhinosinusitis.

PMID- 22952105
TI  - Use of ultrasonography in evaluation of new bone formation in patients treated by
      the method  of Ilizarov.
AB  - BACKGROUND: Lengthening of bones by gradually distracting bone fragments using an
      external apparatus by Ilizarov, is a long process with numerous complications.
      The greatest threats in limb lengthening are poor new bone formation as well as
      premature consolidation of the newly generated bone. The purpose of this study
      was to determine the importance of ultrasonography in evaluation of bone
      formation in limb lengthening. PATIENTS AND METHODS: The study involved 31
      patients, in whom 52 long bones were lengthened by the Ilizarov method at the
      University Clinic for Orthopaedic Surgery in Skopje from 2006 to 2010. The study
      revealed the results of ultrasonographic analysis of new bone formation at four
      various stages of limb lengthening. The analysis of the results of
      ultrasonographic examination of bones throughout the lengthening process was
      based on the form and dimensions of the obtained ultrasonographic parameters-
      indicators of new bone formation--as well as on the appearance of the cortical
      margin at the distraction site. RESULTS: Tiny, solitary and confluent hypo
      echogenic foci developed on sonograms approximately 2 weeks after distraction was
      commenced. At stage I a new cortical margin was detected in 30.77%. The number of
      initial small indicators significantly decreased throughout lengthening. At stage
      IV the solitary indicators rate was 9.51%, whereas the linear indicators rate
      significantly increased from 22.12% at the first stage to 54.3% at the last
      stage. the cortical margin was presented in all 52 bones at III and IV stage of
      lengthening. DISCUSSION AND CONCLUSIONS: Ultrasonography enabled an evaluation of
      the degree of new bone formation and it preceded the radiographic changes at the
      distraction site. This helped to determine the surgical lengthening and to avoid
      numerous complications.

PMID- 22952106
TI  - Significance of ultrasound in the diagnosis  and treatment of achilles tendon
      rupture.
AB  - The aim of this study is to show the importance of ultrasound method in the
      diagnosis of Achilles tendon rupture, the choice of method of treatment and
      monitoring of treatment using the same method. MATERIAL AND METHODS: Between 1999
      and 2009, 134 patients with Achilles tendon rupture were referred to our Clinic.
      66 patients (with a mean age of 38 years) were treated with surgical suture
      followed by plaster immobilization for a period of 8 weeks. 68 patients (with a
      mean age of 42 years) were treated conservatively with plaster immobilization for
      a period of 8 weeks. The follow-up in both groups of patients was 2 years.
      RESULTS: During the clinical and ultrasound monitoring of the patients it was
      proved that repeated rupture of the same tendon occurs on average within 12
      months. Return to sports activities showed in 57% of the conservatively treated
      patients and in 55% of surgically treated patients. The patients with Achilles
      tendon rupture were treated at our Clinic with previously standardized protocol
      which, besides the clinical examination, used the ultrasound method. SUMMARY:
      Ultrasound examination is a very important method in the diagnosis and the choice
      of the method of treatment, as well as in the evaluation of results in patients
      with Achilles tendon rupture, either in operative or conservative treatment.

PMID- 22952107
TI  - Very long Ag nanowire synthesis and its application in a highly transparent,
      conductive and flexible metal electrode touch panel.
AB  - The future electronics will be soft, flexible and even stretchable to be more
      human friendly in the form of wearable computers. However, conventional
      electronic materials are usually brittle. Recently, carbon based materials are
      intensively investigated as a good candidate for flexible electronics but with
      limited mechanical and electrical performances. Metal is still the best material
      for electronics with great electrical properties but with poor transparency and
      mechanical performance. Here we present a simple approach to develop a synthesis
      method for very long metallic nanowires and apply them as new types of high
      performance flexible and transparent metal conductors as an alternative to carbon
      nanotubes, graphene and short nanowire based flexible transparent conductors and
      indium tin oxide based brittle transparent conductors. We found that very long
      metallic nanowire network conductors combined with a low temperature laser nano
      welding process enabled superior transparent flexible conductors with high
      transmittance and high electrical conductivity. Further, we demonstrated highly
      flexible metal conductor LED circuits and transparent touch panels. The highly
      flexible and transparent metal conductors can be mounted on any non-planar
      surfaces and applied for various opto-electronics and ultimately for future
      wearable electronics.

PMID- 22952108
TI  - Low polydispersity (N-ethyl pyrrolidine methacrylamide-co-1-vinylimidazole)
      linear oligomers for gene therapy applications.
AB  - Nonviral methods for gene delivery are becoming ever more prevalent along with
      the need to design new vectors that are highly effective, stable in biological
      fluids, inexpensive, and facile to produce. Here, we synthesize our previously
      reported monomer N-ethyl pyrrolidine methacrylamide (EPA) and evaluate its
      effectiveness in gene vector applications when copolymerized with 1
      vinylimidazole (VI). A range of these novel linear cationic copolymers were
      synthesized via free radical polymerization with low molecular weights
      (oligomers) and low polydispersities showing two pK(a) values as the two co
      monomers are cationic. DNA-polymer polyplexes had average sizes between 100 and
      250nm and zeta-potentials between 10 and 25mV, and a strong dependence of
      composition on the size on the zeta-potential was observed. The cytotoxicity of
      the homopolymers, oligomers, and polyplexes toward human fibroblasts and 3T3
      mouse fibroblasts was evaluated using the MTT and AlamarBlueTM assays, proving
      that formulations could be made with toxicity as low as low molecular weight
      linear poly (dimethylaminoethyl methacrylate) (PDMAEMA). The transfection
      capability of the polyplexes measured using the G-luciferase marker gene far
      superseded PDMAEMA when evaluated in biological conditions. Furthermore, blood
      compatibility studies showed that these new oligomers exhibit no significant
      hemolysis or platelet activation above PBS controls. These new EPA based
      oligomers with low toxicity and ease of scalability show high transfection
      abilities in serum conditions, and blood compatibility showing its potential for
      systemic gene delivery applications.

PMID- 22952109
TI  - Total glossectomy with laryngeal preservation and free flap reconstruction:
      objective functional outcomes and systematic review of the literature.
AB  - OBJECTIVE: Advanced tongue cancer is a devastating diagnosis with potential for
      significant morbidity after treatment. This is especially true for patients
      undergoing total glossectomy with laryngeal preservation (TGLP), free flap
      reconstruction and adjuvant radiotherapy. The goals of this study were to: 1)
      determine long-term objective functional and quality of life outcomes, 2)
      investigate the influence of rehabilitation on functional recovery and 3)
      determine swallowing ability in patients with TGLP. STUDY DESIGN: Prospective
      cohort study and systematic review of the literature. METHODS: Functional
      outcomes data were collected from 2000-2010. Outcomes were measured pre- and 12
      months post-surgery and included: gastrostomy-tube (G-Tube) rates, swallowing
      transit times on video fluoroscopic swallowing studies, speech intelligibility
      and EORTC-H&N 35 quality of life scores. A systematic review of the literature
      was conducted to determine comprehensive long term G-Tube rates. RESULTS: Twelve
      patients were included and eight were still living at 12 months post-surgery.
      Fifty percent of patients in this study and 24% with systematic review used G
      Tubes at 1 year post-surgery. Patients who could swallow did not aspirate, but
      more than doubled swallowing transit times. Spoken sentence intelligibility
      averaged 66% and mean quality of life scores improved 8.9 points 12 months post
      surgery. Patients who attended >80% of swallowing and speech rehabilitation
      sessions demonstrated superior swallowing and speech functional outcomes.
      CONCLUSIONS: Although a potentially morbid treatment, TGLP and free flap
      reconstruction can provide good swallowing and speech outcomes as well as
      meaningful long-term quality of life. Regular attendance of rehabilitation
      sessions is imperative to optimize functional outcomes.

PMID- 22952110
TI  - A trial of drug-induced sleep endoscopy in the surgical management of sleep
      disordered breathing.
AB  - OBJECTIVES/HYPOTHESIS: To determine the reliability and validity of drug-induced
      sleep endoscopy (DISE) for patients undergoing surgery for sleep-disordered
      breathing (SDB). STUDY DESIGN: Non-randomized, prospective clinical trial.
      METHODS: Patients with sleep-disordered breathing were evaluated for multi-level
      upper airway surgery by awake and drug-induced sleep endoscopy to identify levels
      and degree of airway collapse. The reliability of a drug-induced sleep endoscopy
      rating index was assessed by comparing scores of three blinded investigators. The
      validity was assessed by comparison of drug-induced sleep endoscopy index scores
      from awake and drug-induced sleep endoscopy; correlation between drug-induced
      sleep endoscopy scores and Apnea-Hypopnea Index; and determination whether drug
      induced sleep endoscopy affected the original surgical plan. RESULTS: Thirty
      eight patients (22 M, 16 F) underwent preoperative assessment with awake and drug
      induced sleep endoscopy. Drug-induced sleep endoscopy was successfully performed
      in all but one patient (97%) who became combative during propofol infusion. Using
      an internal airway grading scale, drug-induced sleep endoscopy demonstrated more
      severity of collapse than awake endoscopy (P = 0.0001). The surgical plan was
      changed after drug-induced sleep endoscopy in 23 (62%) cases and unchanged in 14
      (38%). The majority (73%) had multi-segmental airway collapse with fewer having
      single-level palatal (16%) or tongue base (11%) collapse. Scoring of drug-induced
      sleep endoscopy videos demonstrated good intrarater (kappa 0.61) and interrater
      (kappa 0.65) correlation. CONCLUSIONS: Drug-induced sleep endoscopy provides more
      clinical information to assess airway function and collapse than awake endoscopy
      alone and assists in the surgical planning. Additional investigation is needed to
      standardize drug-induced sleep endoscopy techniques, training, and
      interpretation.

PMID- 22952111
TI  - Inferior vena cava filters: when, where, why?

PMID- 22952112
TI  - Underlying deep venous abnormalities in patients with unilateral chronic venous
      disease.
AB  - OBJECTIVES: To report our initial experience using direct multidetector computed
      tomography venography (MDCT-V) for imaging lower limb deep veins. CT findings in
      limbs with chronic venous disease (CVD) were compared with contralateral healthy
      limbs. METHODS: MDCT-V with bilateral direct pedal injection of contrast was used
      to image the deep veins in both lower limbs. Eight patients with unilateral lower
      limb CVD of varying severity (according to the Clinico-Etiological-Anatomical and
      Pathological classification [CEAP] class 2-6) were studied. Five patients had
      primary CVD, while three patients had CVD secondary to previous deep vein
      thrombosis. RESULTS: Deep venous obstruction (>50%) or occlusion was identified
      in all CVD limbs and was not seen in contralateral healthy limbs. These lesions
      were not only iliac, were not exclusively present in advanced CVD and were
      independent of the presence or absence of deep venous reflux. CONCLUSION:
      Morphologically significant lesions could be underlying in patients with
      clinically significant CVD. Direct MDCT-V provides clear reconstructable cross
      sectional images of the whole deep venous tree, including infrainguinal areas,
      beyond the reach of intravascular ultrasound. Utilization of new venous imaging
      modalities may uncover previously undiagnosed and potentially treatable venous
      pathology in patients with CVD.

PMID- 22952113
TI  - The effectiveness of tonsillectomy and partial adenoidectomy on obstructive sleep
      apnea in cleft palate patients.
AB  - OBJECTIVES/HYPOTHESIS: The most common cause of pediatric obstructive sleep apnea
      (OSA) is adenotonsillar hypertrophy (ATH). In cleft palate patients, however, the
      obstructive effects of ATH are more severe due to narrow airways. The aim of this
      study was to assess the effectiveness of tonsillectomy and/or partial
      adenoidectomy on OSA in cleft palate patients. STUDY DESIGN: Case series.
      METHODS: Tonsillectomy and/or partial adenoidectomy was performed in 17 repaired
      cleft palate patients with tonsillar and/or adenoid hypertrophy and OSA.
      Apnea/hypopnea (A/H) index and minimum O(2) saturation were measured before and
      after surgery. In addition, because these patients are vulnerable to speech
      impairment after pharyngeal surgery, auditory perceptual assessment (APA) and
      nasometric assessment of speech were performed. RESULTS: The mean preoperative
      A/H index was 17.6 +/- 3.9, and the mean preoperative minimum O(2) saturation was
      88.7 +/- 1.5%. Both parameters improved postoperatively, to 1.9 +/- 2.3 and 93.7
      +/- 1.5% respectively, and the changes were significant (P < 0.001). In 12 cases
      (70.6%), A/H indexes were normalized following surgery. Associated comorbidities
      such as retrognathia and narrow pharyngeal airways may underlie incomplete
      recovery in some cases. There were no significant postoperative changes in APA
      and nasalance scores. CONCLUSIONS: In most cases, tonsillectomy and/or partial
      adenoidectomy is an effective method for treatment of OSA in repaired cleft
      palate patients presenting with tonsillar and/or adenoid hypertrophy. However,
      some cases may need further procedures to relieve airway obstruction due to
      associated comorbidities.

PMID- 22952114
TI  - Effect of the peptide moiety of Lipid II on bacterial transglycosylase.

PMID- 22952115
TI  - Incidence and implication of vocal fold paresis following neonatal cardiac
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: To study the incidence and implications of vocal fold
      paresis (VFP) following congenital neonatal cardiac surgery. STUDY DESIGN:
      Retrospective chart review. METHODS: All neonates who underwent median sternotomy
      for cardiac surgery from May 2007 to May 2008 were evaluated. Flexible
      laryngoscopy was performed to evaluate vocal fold function after extubation.
      Swallow evaluation and a modified barium swallow study were performed prior to
      initiating oral feeding if the initial screening was abnormal. RESULTS: A total
      of 101 neonates underwent cardiac surgery during the study period. Ninety-four
      patients underwent a median sternotomy, and 76 of these were included in the
      study. Fifteen (19.7%) had vocal fold paresis (VFP) postoperatively. Almost 27%
      of the patients with aortic arch surgery had VFP while only 4.1% of the patients
      with nonaortic arch surgery developed VFP (P=0.02) Those patients who underwent
      aortic arch surgery weighed significantly less (P<0.01). All the patients with
      VFP had significant morbidity related to swallowing and nutrition (P=0.01) and
      required longer postsurgical hospitalization (P=0.02). CONCLUSIONS: The reported
      incidence of VFP following cardiac surgery via median sternotomy ranges between
      1.7% and 67% depending on the type of surgery and the weight of the infant at the
      time of surgery. In our cohort, 19.7% had VFP. Surgery requiring aortic arch
      manipulation had a higher incidence of complications and required longer
      hospitalizations. These results may be used to improve informed consent and to
      manage postoperative expectations by identifying patients who are at higher risk
      for complications.

PMID- 22952116
TI  - Central corneal thickness in a Korean population: the Namil Study.
AB  - PURPOSE: We investigated the distribution of central corneal thickness (CCT), and
      its association with age, sex, intraocular pressure (IOP), anterior chamber depth
      (ACD), axial length (AL), and the presence of systemic hypertension and diabetes
      in a Korean population. METHODS: Our study is a population-based glaucoma
      prevalence study of residents aged >=40 years in Namil-meon area, located in
      central South Korea. All subjects underwent a complete ophthalmic examination
      that included CCT measurement with an ultrasonic pachymeter, ACD and AL
      measurements by optical biometry, and Goldmann applanation tonometry. The right
      eye of all subjects was analyzed. RESULTS: The mean (SD) CCT of the 1259 right
      eyes was 530.9 (31.5) MUm. In univariate analysis, a thicker CCT was associated
      with a higher IOP (P < 0.001), a longer AL (P = 0.003), and a younger age (P <
      0.001). ACD was not correlated significantly with CCT (P = 0.087). Men had a 5.7
      MUm higher CCT than women (age adjusted, P = 0.001). Subjects with hypertension
      had a 4.1 MUm lower CCT than those without hypertension (age, sex-adjusted, P =
      0.027), and the presence of diabetes was not associated significantly with CCT
      (age, sex-adjusted, P = 0.892). In multivariate analysis, a higher CCT was
      associated with a higher IOP (P < 0.001), younger age (P = 0.001), male sex (P =
      0.005), and the absence of hypertension (P = 0.018). CONCLUSIONS: The mean CCT of
      a Korean population was 530.9 MUm. CCT was associated with IOP, age, sex, and
      hypertension.

PMID- 22952117
TI  - Diabetes diminishes phosphatidic acid in the retina: a putative mediator for
      reduced mTOR signaling and increased neuronal cell death.
AB  - PURPOSE: We demonstrated previously that pro-survival insulin receptor, PI3K-Akt,
      and p70 S6K signaling is diminished in models of diabetic retinopathy. As
      mammalian target of rapamycin (mTOR), an upstream activator of p70 S6Kinase is,
      in part, regulated by lipid-derived second messengers, such as phosphatidic acid
      (PA), we sought to determine if diminished mTOR/p70 S6Kinase signaling in
      diabetic retinas may reflect diminished PA levels. METHODS: Alterations in PA
      mass from retinas of control and streptozotocin-induced diabetic rats were
      determined by mass spectrometry. The biochemical and biophysical mechanisms
      underlying the actions of PA on insulin-activated mTOR/p70 S6Kinase signaling
      were determined using R28 retinal neuronal cells. RESULTS: We demonstrate a
      significant decrease in PA in R28 retinal neuronal cells exposed to hyperglycemia
      as well as in streptozotocin-induced diabetic rat retinas. Exogenous PA augmented
      insulin-induced protection from interleukin-1beta-induced apoptosis. Moreover,
      exogenous PA and insulin cooperatively activated mTOR survival pathways in R28
      neuronal cultures. Exogenous PA colocalized with activated mTOR/p70 S6kinase
      signaling elements within lipid microdomains. The biochemical consequences of
      this biophysical mechanism is reflected by differential phosphorylation of
      tuberin at threonine 1462 and serine 1798, respectively, by PA and insulin, which
      reduce this suppressor of mTOR/S6Kinase signaling within lipid microdomains.
      CONCLUSIONS: These results identify PA-enriched microdomains as a putative lipid
      based signaling element responsible for mTOR-dependent retinal neuronal survival.
      Moreover, diabetic retinal neuronal apoptosis may reflect diminished PA mass.
      Elevating PA concentrations and restoring mTOR signaling may be an effective
      therapeutic modality to reduce neuronal cell death in diabetic retinopathy.

PMID- 22952118
TI  - CXCL1-deficient mice are highly sensitive to pseudomonas aeruginosa but not
      herpes simplex virus type 1 corneal infection.
AB  - PURPOSE: To determine the role of the chemokine CXCL1 on leukocyte recruitment,
      cytokine production and host resistance during HSV-1 and Pseudomonas aeruginosa
      infection. METHODS: Viral titer and bacterial load were compared following
      infection of wild-type (WT) and CXCL1(-/-) mice. Corneal leukocyte recruitment
      was determined using flow cytometry. Cytokine levels were assessed by luminex
      based suspension arrays. Hematoxylin and eosin (H&E) staining, confocal
      microscopy, and optical coherence tomography (OCT) were used to visualize
      leukocyte recruitment and corneal thickening. RESULTS: HSV-1-infected WT and
      CXCL1(-/-) mice possessed similar viral titers in the cornea during late acute
      infection. Flow cytometry analysis detected similar leukocyte levels in the
      cornea following infection as well. By comparison, there was a significant
      increase in P. aeruginosa recovered from CXCL1(-/-) corneas as compared with WT
      mice. Imaging analysis and histochemical staining revealed impaired leukocyte
      recruitment to the central cornea and earlier corneal thickening in CXCL1(-/-)
      mice. IFN-gamma, CCL2, and CCL5 protein levels were similar between WT and CXCL1(
      /-) corneas following HSV-1 or P. aeruginosa infection. However, CXCL2 levels
      were significantly reduced in the CXCL1(-/-) corneas following either infection.
      CONCLUSIONS: The absence of CXCL1 and CXCL2 expression significantly impairs the
      ability of the host to control P. aeruginosa replication through the recruitment
      of leukocytes to the central cornea. In contrast, CXCL1, CXCL2, and the cells
      they recruit, are not required for HSV-1 clearance during acute infection.

PMID- 22952119
TI  - Segmentational analysis of retinal thickness after vitrectomy in diabetic macular
      edema.
AB  - PURPOSE: To measure the inner and outer retinal thicknesses on spectral-domain
      optical coherence tomography (SD-OCT) and evaluate their association with logMAR
      after vitrectomy for diabetic macular edema (DME). METHODS: In this retrospective
      case series, there were 55 consecutive eyes with DME for which vitrectomy was
      performed. The total retinal thickness, the inner thickness (from the innermost
      of the retina to the inner nuclear layer), and the outer thickness (from the
      outer plexiform layer to the retinal pigment epithelium) in the parafoveal
      subfields were measured manually, and the association with logMAR was evaluated.
      RESULTS: The total retinal thicknesses in the central, nasal, and inferior
      subfields were significantly (r = 0.37, P = 0.005; r = 0.29, P = 0.032; r = 0.33,
      P = 0.015, respectively) associated with the baseline logMAR; no subfield
      thickness was correlated with the logMAR at the final visit. However,
      segmentational analysis showed that the outer retinal thickness of the temporal
      subfield was associated with disruption of the junction between the inner and
      outer segments at the fovea (P = 0.021 and P = 0.005) and negatively correlated
      with the logMAR (r = -0.37, P = 0.006 and r = -0.28, P = 0.042) at the 6-month
      and final visit. The inner thickness of the nasal subfield did not change after
      vitrectomy compared with the other subfields and the outer thickness of all
      subfields in the parafoveal area; the baseline nasal total thickness was
      correlated most significantly with the logMAR (r = 0.40, P = 0.002 and r = 0.37,
      P = 0.006) at the 6-month and final visits. CONCLUSIONS: Segmentational analysis
      provided useful information for considering the prognosis and pathogenesis after
      vitrectomy for DME.

PMID- 22952120
TI  - Is whole-body hydration an important consideration in dry eye?
AB  - PURPOSE: To identify if whole-body hydration plays an important role in dry eye
      (DE). We hypothesized that individuals classified as DE have higher plasma
      osmolality (Posm), indicating suboptimal hydration, compared with those
      classified as non-DE. METHODS: Using a hospital-based observational cross
      sectional design, assessment of DE and hydration was performed upon admission in
      111 participants (N = 56 males and 55 females; mean +/- SD age 77 +/- 8 years).
      Assessments of DE included tear osmolarity (Tosm), the 5-item dry eye
      questionnaire (DEQ-5), rating of eye dryness using a visual analogue scale (VAS),
      and noninvasive tear film breakup time (NITBUT). Hydration assessment was
      performed by measuring Posm using freezing-point depression osmometry. RESULTS:
      Posm was higher in DE than control (CON), indicating suboptimal hydration when
      using the 316 mOsm/L Tosm cutoff for DE (mean Posm + 11 mOsm/kg versus CON, P =
      0.004, Cohen's effect size [d]) = 0.83) and the more conservative Tosm
      classification for DE where Tosm >324 and CON <308 mOsm/L (mean Posm + 12 mOsm/kg
      versus CON, P = 0.006, d = 0.94). Posm was also higher in DE than CON when using
      composite DE assessments, including Tosm and DEQ-5 (P = 0.021, d = 1.07); Tosm
      and NITBUT (P = 0.013, d = 1.08); and the VAS and DEQ-5 (P = 0.034, d = 0.58).
      CONCLUSIONS: These are the first published data to show that individuals
      classified as DE have higher Posm, indicating suboptimal hydration, compared with
      non-DE. These findings indicate that whole-body hydration is an important
      consideration in DE.

PMID- 22952121
TI  - Factors that influence standard automated perimetry test results in glaucoma:
      test reliability, technician experience, time of day, and season.
AB  - PURPOSE: To determine the influence of several factors on standard automated
      perimetry test results in glaucoma. METHODS: Longitudinal Humphrey field analyzer
      30-2 Swedish interactive threshold algorithm data from 160 eyes of 160 glaucoma
      patients were used. The influence of technician experience, time of day, and
      season on the mean deviation (MD) was determined by performing linear regression
      analysis of MD against time on a series of visual fields and subsequently
      performing a multiple linear regression analysis with the MD residuals as
      dependent variable and the factors mentioned above as independent variables.
      Analyses were performed with and without adjustment for the test reliability
      (fixation losses and false-positive and false-negative answers) and with and
      without stratification according to disease stage (baseline MD). RESULTS: Mean
      follow-up was 9.4 years, with on average 10.8 tests per patient. Technician
      experience, time of day, and season were associated with the MD. Approximately
      0.2 dB lower MD values were found for inexperienced technicians (P < 0.001),
      tests performed after lunch (P < 0.001), and tests performed in the summer or
      autumn (P < 0.001). The effects of time of day and season appeared to depend on
      disease stage. Independent of these effects, the percentage of false-positive
      answers strongly influenced the MD with a 1 dB increase in MD per 10% increase in
      false-positive answers. CONCLUSIONS: Technician experience, time of day, season,
      and the percentage of false-positive answers have a significant influence on the
      MD of standard automated perimetry.

PMID- 22952123
TI  - Visual field progression in glaucoma: estimating the overall significance of
      deterioration with permutation analyses of pointwise linear regression (PoPLR).
AB  - PURPOSE: To establish a method for estimating the overall statistical
      significance of visual field deterioration from an individual patient's data, and
      to compare its performance to pointwise linear regression. METHODS: The Truncated
      Product Method was used to calculate a statistic S that combines evidence of
      deterioration from individual test locations in the visual field. The overall
      statistical significance (P value) of visual field deterioration was inferred by
      comparing S with its permutation distribution, derived from repeated reordering
      of the visual field series. Permutation of pointwise linear regression (PoPLR)
      and pointwise linear regression were evaluated in data from patients with
      glaucoma (944 eyes, median mean deviation -2.9 dB, interquartile range: -6.3, 
      1.2 dB) followed for more than 4 years (median 10 examinations over 8 years).
      False-positive rates were estimated from randomly reordered series of this
      dataset, and hit rates (proportion of eyes with significant deterioration) were
      estimated from the original series. RESULTS: The false-positive rates of PoPLR
      were indistinguishable from the corresponding nominal significance levels and
      were independent of baseline visual field damage and length of follow-up. At P <
      0.05, the hit rates of PoPLR were 12, 29, and 42%, at the fifth, eighth, and
      final examinations, respectively, and at matching specificities they were
      consistently higher than those of pointwise linear regression. CONCLUSIONS: In
      contrast to population-based progression analyses, PoPLR provides a continuous
      estimate of statistical significance for visual field deterioration
      individualized to a particular patient's data. This allows close control over
      specificity, essential for monitoring patients in clinical practice and in
      clinical trials.

PMID- 22952122
TI  - Menthol activation of corneal cool cells induces TRPM8-mediated lacrimation but
      not nociceptive responses in rodents.
AB  - PURPOSE: Stimulation to the cornea via noxious chemical and mechanical means
      evokes tearing, blinking, and pain. In contrast, mild cooling of the ocular
      surface has been reported to increase lacrimation via activation of corneal cool
      primary afferent neurons. The purpose of our study was to determine whether
      menthol induces corneal cool cell activity and lacrimation via the transient
      receptor potential melastatin-8 (TRPM8) channel without evoking nociceptive
      responses. METHODS: Tear measurements were made using a cotton thread in TRPM8
      wild type and knockout mice after application of menthol (0.05-50 mM) to the
      cornea. In additional studies, nocifensive responses (eye swiping and lid
      closure) were quantified following cornea menthol application. Trigeminal
      ganglion electrophysiologic single unit recordings were performed in rats to
      determine the effect of low and high concentrations of menthol on corneal cool
      cells. RESULTS: At low concentrations, menthol increased tear production in TRPM8
      wild type and heterozygous animals, but had no effect in TRPM8 knockout mice,
      while nocifensive responses remained unaffected. At the highest concentration,
      menthol (50 mM) increased tearing and nocifensive responses in TRPM8 wild type
      and knockout animals. A low concentration of menthol (0.1 mM) increased cool cell
      activity, yet a high concentration of menthol (50 mM) had no effect. CONCLUSIONS:
      These studies indicated that low concentrations of menthol can increase
      lacrimation via TRPM8 channels without evoking nocifensive behaviors. At high
      concentrations, menthol can induce lacrimation and nocifensive behaviors in a
      TRPM8 independent mechanism. The increase in lacrimation is likely due to an
      increase in cool cell activity.

PMID- 22952124
TI  - Phosphomimetic mutants of pigment epithelium-derived factor with enhanced anti
      choroidal melanoma cell activity in vitro and in vivo.
AB  - PURPOSE: Currently, choroidal melanoma is chemoresistant and there is no routine
      adjuvant chemotherapy for it. We investigated whether pigment epithelium-derived
      factor (PEDF) and its triple phosphomimetic mutants could more efficiently
      suppress melanoma tumor growth and metastasis, as well as how the triple
      phosphomimetic mutants act as antitumor agents. METHODS: Phosphomimetic mutants
      of PEDF were constructed by site mutagenesis. Lentiviruses carrying wild type
      (WT) PEDF, S24E114E227A (EEA)-PEDF, and S24E114E227E (EEE)-PEDF were produced in
      293 fast-growing, highly transfectable (FT) cells and used to infect human
      choroidal melanoma cell line (OCM-1). The growth, migration, invasion and
      metastasis abilities of OCM-1 cells expressing WT-PEDF, EEA-PEDF or EEE-PEDF were
      investigated in vitro and in vivo, while the underlying mechanism of PEDF
      phosphomimetic mutants were investigated via Western blotting. RESULTS: OCM-1
      cells infected with lentiviruses carrying WT-PEDF, EEA-PEDF, and EEE-PEDF
      displayed reduced proliferation, migration and invasion abilities, and were more
      prone to apoptosis. Cell media containing WT-PEDF, EEA-PEDF, or EEE-PEDF protein
      inhibited the tube forming capacity of human umbilical vein endothelial cells
      (HUVEC) in vitro. OCM-1 cells expressing WT-PEDF, EEA-PEDF, or EEE-PEDF displayed
      significantly reduced tumor growth and metastasis in the melanoma xenograft of
      nude mice models, with the PEDF mutants displaying much stronger effects than the
      wild type. The antitumor effects of PEDF are associated with the inhibition of
      VEGF and nuclear factor kappa-B (NF-kappaB) expression, as well as further
      inhibition of Akt phosphorylation. CONCLUSIONS: The phosphomimetic mutants of
      PEDF showed enhanced anti-melanoma activity by directly affecting tumor cells and
      indirectly affecting angiogenesis. These findings encourage the development of
      PEDF mutants as innovative anticancer agents.

PMID- 22952125
TI  - Migration of toxoplasma gondii-infected dendritic cells across human retinal
      vascular endothelium.
AB  - PURPOSE: Toxoplasma gondii, the parasite responsible for ocular toxoplasmosis,
      accesses the retina from the bloodstream. We investigated the dendritic cell as a
      potential taxi for T. gondii tachyzoites moving across the human retinal
      endothelium, and examined the participation of adhesion molecules and chemokines
      in this process. METHODS: CD14-positive monocytes were isolated from human
      peripheral blood by antibody-mediated cell enrichment, and cultured in
      granulocyte-macrophage colony-stimulating factor and interleukin-4 to generate
      dendritic cells. Transmigration assays were performed over 18 hours in transwells
      seeded with human retinal endothelial cells and using dendritic cells exposed to
      laboratory or natural strains of T. gondii tachyzoites. Parasites were tagged
      with yellow fluorescent protein to verify infection. In some experiments,
      endothelial monolayers were preincubated with antibody directed against adhesion
      molecules, or chemokine was added to lower chambers of transwells. RESULTS: Human
      monocyte-derived dendritic cell preparations infected with laboratory or natural
      strain T. gondii tachyzoites transmigrated in larger numbers across simulated
      human retinal endothelium than uninfected dendritic cells (P <= 0.0004 in 5 of 6
      experiments). Antibody blockade of intercellular adhesion molecule (ICAM)-1,
      vascular cell adhesion molecule (VCAM)-1, and activated leukocyte cell adhesion
      molecule (ALCAM) inhibited transmigration (P <= 0.007), and CCL21 or CXCL10
      increased transmigration (P <= 0.031). CONCLUSIONS: Transmigration of human
      dendritic cells across retinal endothelium is increased following infection with
      T. gondii. Movement may be impacted by locally produced chemokines and is
      mediated in part by ICAM-1, VCAM-1, and ALCAM. These findings have implications
      for development of novel therapeutics aimed at preventing retinal infection by T.
      gondii.

PMID- 22952127
TI  - The impact of a palliative care program in a rural Appalachian community
      hospital: a quality improvement process.
AB  - BACKGROUND: Hospital inpatient palliative care consultation services (PCCSs)
      provide high-quality, comprehensive care for seriously ill patients and their
      families. The objective of the Palliative Care Impact Study was to evaluate the
      impact of a PCCS in a rural Appalachian community hospital in 4 domains:
      clinical, customer, operational, and financial. METHODS AND RESULTS: A
      nonrandomized preintervention-postintervention study enrolled 25 patients. We
      collected data in the 4 domains listed above after a palliative care (PC)
      consultation and compared them with preconsultation data. Findings demonstrated a
      statistically significant improvement in pain and symptom burden scores; customer
      metrics produced an excellent rating of 88.5% by patients and families and
      physician/providers; with an associated cost savings of $521 per patient per day
      after PC consultation was complete.

PMID- 22952126
TI  - Choroidal thinning in diabetes type 1 detected by 3-dimensional 1060 nm optical
      coherence tomography.
AB  - PURPOSE: To map choroidal (ChT) and retinal thickness (RT) in patients with
      diabetes type 1 with and without maculopathy and retinopathy in order to compare
      them with healthy subjects using high speed 3-dimensional (3D) 1060 nm optical
      coherence tomography (OCT). METHODS: Thirty-three eyes from 33 diabetes type 1
      subjects (23-57 years, 15 male) divided into groups of without pathology (NDR)
      and with pathology (DR; including microaneurysms, exudates, clinically
      significant macular-oedema and proliferative retinopathy) were compared with 20
      healthy axial eye length and age-matched subjects (24-57 years, 9 male), imaged
      by high speed (60.000 A-scans/s) 3D 1060 nm OCT performed over 36 degrees  * 36
      degrees  field of view. Ocular health status, disease duration, body mass index,
      haemoglobin-A1c, and blood pressure (bp) measurements were recorded. Subfoveal
      ChT, and 2D topographic maps between retinal pigment epithelium and the
      choroidal/scleral-interface, were automatically generated and statistically
      analyzed. RESULTS: Subfoveal ChT (mean +/- SD, MUm) for healthy eyes was 388 +/-
      109; significantly thicker than all diabetic groups, 291 +/- 64 for NDR, and 303
      +/- 82 for DR (ANOVA P < 0.004, Tukey P = 0.01 for NDR and DR). Thinning did not
      relate to recorded factors (multi-regression analysis, P > 0.05). Compared with
      healthy eyes and the NDR, the averaged DR ChT-map demonstrated temporal thinning
      that extended superiorly and temporal-inferiorly (unpaired t-test, P < 0.05).
      Foveal RT and RT-maps showed no statistically significant difference between
      groups (mean SD, MUm, healthy 212 +/- 17, NDR 217 +/- 15, DR 216 +/- 27, ANOVA P
      > 0.05). CONCLUSIONS: ChT is decreased in diabetes type 1, independent of the
      absence of pathology and of diabetic disease duration. In eyes with pathology, 3D
      1060 nm OCT averaged maps showed an extension of the thinning area matching
      retinal lesions and suggesting its involvement on onset or progression of
      disease.

PMID- 22952128
TI  - Racial/ethnic perspectives on the quality of hospice care.
AB  - Diversity in the US population is increasing, and evaluating the quality of
      culturally sensitive hospice care is important. A survey design was used to
      collect data from 743 patients enrolled in hospice or their family members or
      caregivers. Race/ethnicity was not significantly associated with any of the
      hospice interventions or outcomes. Patients were less likely to be satisfied with
      the overall hospice care (OR = 0.23, 95% CI = 0.065-0.796, P = .021) compared to
      other type of respondents.  Satisfaction with emotional support was substantially
      associated with the increased likelihood of satisfaction with pain management (OR
      = 3.82, 95% CI = 1.66-8.83, P = .002), satisfaction with other symptom management
      (OR = 6.17, 95% CI = 2.80-13.64, P < .001), and of overall satisfaction with
      hospice care (OR = 20.22, 95% CI = 8.64-47.35, P < .001).

PMID- 22952129
TI  - Spirituality, religiosity, and spiritual pain among caregivers of patients with
      advanced cancer.
AB  - BACKGROUND: Caregivers of patients with advanced cancer often face physical,
      social, and emotional distress as well as spiritual pain. Limited research has
      focused on the spiritual aspects of caregivers' suffering in the palliative care
      setting. METHODS: We interviewed 43 caregivers of patients with advanced cancer
      in our palliative care outpatient clinic. We determined demographic
      characteristics, religious affiliation, and relationship to the patient. Levels
      of spirituality, religiosity, and spiritual pain were self-reported using numeric
      rating scales (0 = lowest; 10 = highest). The participants completed various
      validated questionnaires to assess sleep disturbances, psychosocial distress,
      coping skills, and quality of life (QOL). RESULTS: The median age was 52 years
      (range, 21-83); 29 (67%) were women, 34 (78%) were white, 7 (17%) were African
      American, and 2 (5%) were Hispanic; 39 (91%) were Christian, 1 (2%) was Jewish,
      and 1 (2%) was agnostic; 37 (86%) were married; 18 (42%) were working full time;
      and 25 (58%) were spouses. All considered themselves spiritual, and 98%
      considered themselves religious, with median scores of 8 (interquartile range, 6
      10) and 8 (interquartile range, 4-9), respectively. All the caregivers reported
      that spirituality and religiosity helped them cope with their loved one's
      illness, and many reported that spirituality and religiosity had a positive
      impact on their loved one's physical (58%) and emotional (76%) symptoms.
      Spiritual pain was reported by 23 (58%), with a median score of 5 (interquartile
      range, 2-8). Caregivers with spiritual pain had higher levels of anxiety (median
      10 vs 4; P = .002), depression (6 vs 2; P = .006), and denial (3 vs 2; P = .01);
      more behavioral disengagement (3 vs 2; P = 0.011) more dysfunctional coping
      strategies (19 vs 16; P < .001) and worse QOL (70 vs 51; P < .001) than those who
      did not have spiritual pain. CONCLUSIONS: The majority of caregivers of patients
      with advanced cancer considered themselves spiritual and religious. Despite this,
      there is high prevalence of spiritual pain in this population. Caregivers with
      spiritual pain experienced worse psychological distress and worse QOL. These
      findings support the importance of spiritual assessment of and spiritual support
      for caregivers in this setting.

PMID- 22952130
TI  - Seroprevalence of Neospora caninum, paratuberculosis and Q fever in cattle in
      Belgium in 2009-2010.

PMID- 22952131
TI  - Vaccination of sows reduces the prevalence of PCV-2 viraemia in their piglets
      under field conditions.
AB  - The objectives of this study were to further understand vertical transmission of
      porcine circovirus type 2 (PCV-2) and the effect of dam vaccination on PCV-2
      viraemia in newborn piglets. Randomly selected sows from each of two breeding
      herds were designated as non-vaccinated or vaccinated groups. A commercial
      inactivated PCV-2 vaccine was administered at weaning and 18 days later to half
      of the sows on each farm. At parturition, colostrum was collected from 70 dams on
      each farm and postsuckle (Farm 1) or presuckle blood (Farm 2) was collected from
      five randomly selected piglets per litter. Colostrum samples had an anti-PCV-2
      antibody prevalence of 98.5 per cent (135/137) with significantly (P = 0.0039)
      higher concentrations in vaccinated dams. Among piglets, 43.9 per cent (301/685)
      were seropositive for PCV-2 and 11.7 per cent (80/686) were PCV-2 DNA-positive.
      All the PCV-2 DNA-positive samples were further characterised and 28 were PCV-2a,
      28 PCV-2b, and five mixed PCV-2a and PCV-2b infection. The prevalence of PCV-2
      DNA in piglets was lower (0.7-22.8 per cent) compared with previous studies (44.8
      90 per cent) indicating a change in PCV-2 ecology likely due to wide use of
      vaccination. Under the study conditions, dam vaccination reduced PCV-2 viraemia
      in the offspring with colostrum access.

PMID- 22952132
TI  - Partial brachial plexus paresis in three calves.
AB  - Partial brachial plexus paresis was diagnosed in three calves with unilateral
      functional lameness in a forelimb based on clinical and neurologic examinations.
      Clinical signs of radial nerve paresis were the main presenting problems.
      Electromyography was used to identify the affected nerves with the calves under
      general anaesthesia. Abnormal spontaneous activity of denervated muscles showed
      that the radial, musculocutaneous, median and ulnar nerves were compromised. The
      calves were treated medically, using splint bandages, and with physiotherapy. All
      calves regained function of the affected legs and normal weight bearing.

PMID- 22952133
TI  - Hypervitaminosis A in lambs fed milk replacer.

PMID- 22952134
TI  - Evidence of H3N2 canine influenza virus infection before 2007.

PMID- 22952135
TI  - Feline sarcoptic mange in the UK: a case report.

PMID- 22952136
TI  - Are kissing gourami specialized for substrate-feeding? Prey capture kinematics of
      Helostoma temminckii and other anabantoid fishes.
AB  - Helostoma temminckii are known for a "kissing" behavior, which is often used in
      intraspecific interactions, and an unusual cranial morphology that is
      characterized by an intramandibular joint (IMJ). The IMJ is located within the
      lower jaw and aids in generating the eponymous kissing movement. In other teleost
      linages the IMJ is associated with the adoption of a substrate-grazing foraging
      habit. However, because of anatomical modifications of the gill-rakers, Helostoma
      has been considered a midwater filter-feeding species. We offered midwater,
      benthic, and attached food to Helostoma, Betta, and two "true" osphronemid
      gouramis, to ask: (1) how do food capture kinematics differ in different foraging
      contexts; and (2) are Helostoma feeding kinematics distinct when compared with
      closely related anabantoids that lack an IMJ? For all anabantoid species except
      Helostoma, benthic prey were captured using a greater contribution of effective
      suction relative to midwater prey, though Helostoma was rarely willing to feed in
      the midwater. Helostoma individuals produced relatively less suction than other
      species regardless of the food type. Helostoma produced a much larger gape and
      more premaxillary protrusion than other species, but also took longer to do so.
      We suggest that the jaw morphology of Helostoma facilitates an extremely large
      mouth-gape to enhance substrate-scraping. The large amplitude mouth-opening that
      characterizes substrate-feeding may represent a functional trade-off, whereby the
      enhanced ability to procure food from the substrate is accompanied by a
      concomitant reduction in the ability to produce suction.

PMID- 22952137
TI  - Opposition of carbohydrate in a mouth-rinse solution to the detrimental effect of
      mouth rinsing during cycling time trials.
AB  - Studies have reported that rinsing the mouth with a carbohydrate (CHO) solution
      improves cycling time-trial performance compared with rinsing with a placebo
      solution. However, no studies have compared the effect of mouth rinsing with a no
      mouth-rinse control condition. The aim of this study was to compare the effects
      of a CHO mouth rinse with those of a placebo rinse and a no-rinse condition. Ten
      male cyclists completed three 1,000-kJ cycling time trials in a randomized,
      counterbalanced order. At every 12.5% of the time trial completed, participants
      were required to rinse their mouths for 5 s with either a 6.4% maltodextrin
      solution (CHO), water (WA), or no solution (CON). Heart rate and ratings of
      perceived exertion (RPE) were recorded every 25% of the time trial completed.
      Time to completion was faster in both CHO (65.7 +/- 11.07 min) and CON (67.6 +/-
      12.68 min) than in WA (69.4 +/- 13.81 min; p = .013 and p = .042, respectively).
      The difference between CHO and CON approached significance (p = .086). There were
      no differences in heart rate or RPE between any conditions. In summary, repeated
      mouth rinsing with water results in decreased performance relative to not rinsing
      at all. Adding CHO to the rinse solution appears to oppose this fall in
      performance, possibly providing additional benefits to performance compared with
      not rinsing the mouth at all. This brings into question the magnitude of the
      effect of CHO mouth rinsing reported in previous studies that did not include a
      no-rinse condition.

PMID- 22952138
TI  - EACPR/AHA Joint Scientific Statement. Clinical recommendations for
      cardiopulmonary exercise testing data assessment in specific patient populations.

PMID- 22952139
TI  - Management of heart failure: are specialists really needed?

PMID- 22952140
TI  - Complete genome sequence of Acinetobacter baumannii MDR-TJ and insights into its
      mechanism of antibiotic resistance.
AB  - OBJECTIVES: To determine the genome sequence of Acinetobacter baumannii strain
      MDR-TJ and characterize the mechanisms of multidrug resistance in this strain.
      METHODS: The whole-genome sequence was determined using Roche 454 GS FLX
      Titanium. Subsequently, the gaps were closed by sequencing PCR products. The
      genome of strain MDR-TJ was annotated using IMG ER, the RAST annotation server
      and the BASys bacterial annotation system. The comM gene of MDR-TJ was examined
      to identify a possible antibiotic resistance island. Based on the results of
      multilocus sequence typing, we investigated seven multidrug-resistant A.
      baumannii strains belonging to global clone 2 (GC2) isolated from Asia, Australia
      and Europe to determine the backbone shared by resistance islands of GC2
      isolates. RESULTS: The A. baumannii strain MDR-TJ genome consists of a circular
      chromosome and a plasmid, pABTJ1. Strain MDR-TJ was assigned to sequence type
      ST2. Strain MDR-TJ harbours a 41.6 kb resistance island designated RI(MDR-TJ),
      which can be derived from the backbone of Tn6167 through the insertion of a
      Tn6022 into the 3'-end of the tetA(B) gene. Comparative analysis showed that
      transposon Tn6022 and its truncated forms prevailed in the antibiotic resistance
      islands of GC2 isolates. The carbapenem resistance gene bla(OXA-23) carried by
      transposon Tn2009 is located on a putatively conjugative plasmid, pABTJ1.
      CONCLUSIONS: A. baumannii strain MDR-TJ belongs to GC2 and is resistant to
      multiple antibiotics. A. baumannii MDR-TJ harbours a genomic resistance island
      that interrupts the comM gene. The carbapenem resistance of MDR-TJ is mediated by
      a putatively conjugative plasmid, pABTJ1.

PMID- 22952141
TI  - Temperature effects on the biomechanics of prey capture in the frog Rana pipiens.
AB  - Movements of many animals are powered by a combination of active shortening of
      muscles and recoil of elastic structures. Movements that rely primarily on
      elastic recoil, such as the explosive locomotor and feeding movements of many
      ectotherms, have been shown to exhibit lower thermal dependence than muscle
      powered movements because elastically powered movements circumvent the effects of
      temperature on muscle contractile dynamics. To determine if elastic recoil
      contributes to the ballistic mouth opening and tongue projection of the frog Rana
      pipiens, we examined feeding kinematics and dynamics of tongue and jaw movements
      at three ambient temperatures (10, 15, and 25 degrees C) using 6,000 Hz image
      sequences. We found that ballistic mouth opening exhibits high instantaneous
      power (up to 1,783 W kg(-1) of muscle mass) and its dynamics have low thermal
      dependence (Q(10) values of 1.02-1.37), indicating the contribution of elastic
      recoil. The dynamics of tongue projection are more thermally dependent (Q(10) of
      1.35-2.51) and likely involve muscle activity during the movement. Mouth opening
      during prey transport, as well as tongue retraction and mouth closing showed
      little evidence of elastic recoil and their dynamics show relatively high thermal
      dependence (Q(10) of 1.38-1.89). R. pipiens shows lower thermal robustness and
      power of tongue projection than ballistic-tongued Bufo terrestris which displays
      complete thermal independence, suggesting that in Rana tongue projection is not
      as tightly coupled to jaw depression as in toads. We propose that thermal
      experiments may be useful in probing for elastic mechanisms in other
      biomechanical systems.

PMID- 22952142
TI  - Cloning, expression, and localization of two types of fast skeletal myosin heavy
      chain genes from black tiger and Pacific white shrimps.
AB  - The physiology and biochemistry of skeletal muscles in shrimps have been poorly
      understood compared with those from vertebrates. The present study was conducted
      focusing on myosin, the major protein in skeletal muscle, from adult specimens of
      black tiger Penaeus monodon and Pacific white Penaeus vannamei shrimps. Two genes
      encoding myosin heavy chain (MHC), a large subunit of the myosin molecule, were
      cloned from abdominal fast skeletal muscle and defined as MHCa and MHCb according
      to our previous study on kuruma shrimp Marsupenaeus japonicus. Random cloning
      demonstrated that the MHCb gene (MHCb) was expressed more abundantly than MHCa.
      The full-length cDNA clones of MHCa and MHCb from black tiger shrimp consisted of
      5,926 and 5,914 bp, respectively, which encoded 1,914 and 1,909 amino acids,
      respectively, whereas those from Pacific white shrimp consisted of 5,923 and
      5,908 bp, respectively, which encoded 1,913 and 1,909 amino acids, respectively.
      Both MHCa and MHCb were considered to be fast muscle type due to their strict
      localization in fast muscle. The amino acid identities between MHCa and MHCb of
      black tiger shrimp were 77%, 60%, and 73% in the regions of subfragment-1 (S1),
      subfragment-2 (S2) and light meromyosin (LMM), respectively, with 71% in total,
      whereas those of Pacific white shrimp were 78%, 60%, and 73% in the regions of
      S1, S2, and LMM, respectively, with 72% in total. In situ hybridization and
      northern blot analysis using different regions from abdominal muscle demonstrated
      different localizations of MHCa and MHCb transcripts in this muscle, suggesting
      their distinct physiological functions.

PMID- 22952143
TI  - Lower body surface area is highly related to mortality due to stroke or systemic
      bleeding in patients receiving an axial flow blood pump as a left ventricular
      assist device.
AB  - OBJECTIVES: Even though left ventricular assist devices (LVADs) may fit into the
      bodies of small adult patients, their prognosis is worse than that of larger
      patients. We investigated the relationship between lethal complications and the
      body surface area (BSA) in patients who received an LVAD. METHODS: Our study
      included 167 patients who received a BerlinHeart INCOR LVAD in our centre. The
      median BSA was 2.00 m(2) (range: 1.56-2.47 m2). From the line graph showing the
      relationship between the BSA for the cut-off point and the P-value of the log
      rank test for the Kaplan-Meier probability of freedom from events, the definitive
      cut-off point was determined on the basis that, with a decrease in the BSA below
      this value, the P-value gradually increases. RESULTS: For freedom from death due
      to stroke or systemic bleeding, a definitive cut-off point existed and this was a
      BSA of 1.867 m(2). For freedom from death due to sepsis, no definitive cut-off
      point was found. The multivariate Cox analysis revealed that a BSA of <1.867 m(2)
      was an independent risk factor for death due to stroke or systemic bleeding
      (hazard ratio: 2.665, 95% confidence interval: 1.349-5.265, P = 0.0048). One-year
      freedom from death due to stroke or systemic bleeding during the VAD support was
      49.1% in patients with a BSA of <1.867 m(2) (n = 42) and 82.7% in those with a
      BSA of >= 1.867 m(2) (n = 125; P = 0.0033). CONCLUSIONS: The lower BSA is an
      independent risk factor for mortality due to stroke or systemic bleeding during
      the VAD support.

PMID- 22952144
TI  - Endoscopic mitral valve reconstruction and percutaneous mitral clipping: what is
      the best solution for our patients?

PMID- 22952145
TI  - Steroid concentrations and immunoexpression of steroidogenic enzymes in ovaries
      of aged bank voles: effect of photoperiod.
AB  - The main objective of the present study was to establish morphological and
      steroidogenic changes occurring in the ovaries of senescent bank voles, with
      respect to the photoperiod of rearing. Obtained results revealed less pronounced
      changes in the ovaries of females reared in a long photoperiod (LD). Their gonads
      still possessed some healthy follicles and old corpora lutea (CLs). Senescence
      related changes encompassed the presence of abnormal follicles, large regions
      containing extra-follicular luteinized granulosa cells and numerous clusters of
      hypertrophied theca/interstitial cells, exhibiting strong expression of 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) and much weaker that of cytochrome
      P450c17. More pronounced changes were observed in animals reared in short day
      (SD) conditions and included the presence of only few, usually abnormal follicles
      and/or remnants of CLs in the surface region, and the isle-like clusters of cells
      in the ovarian medulla. The clusters were composed of cells generally featuring
      strong 3beta-HSD and/or P450c17 immunoreaction. Steroid content analysis revealed
      that progesterone dominated in the ovaries of LD bank voles and androgens in SD
      animals, while estradiol content was very low in both investigated groups. These
      studies showed for the first time morphological and steroidogenic changes found
      in the ovaries of senescent bank voles and indicated an important role of length
      light conditions in the process of reproductive aging.

PMID- 22952146
TI  - 'The chicken or the egg?' dilemma strikes back for the controlling mechanism in
      chordoma(#).
AB  - Chordoma is a rare malignant tumour of bone showing notochordal differentiation
      with characteristic expression of the transcription factor brachyury (T). Next to
      giving insight into its differentiation spectrum, the expression of T can be used
      as an adjunct diagnostic tool. The expression of brachyury in chordoma is
      necessary to maintain cell proliferation in chordoma cell lines, indicating that
      in chordoma it might be a master regulator of oncogenesis. Identification and
      mapping of the full gene regulatory network in a recent work in The Journal of
      Pathology by Nelson and colleagues not only shed light on involved pathways but
      also indicated pathways for targeted therapy, including brachyury itself.

PMID- 22952147
TI  - Isolated limb perfusion: is it possible to increase cancer treatment efficacy by
      simultaneous glucose deprivation?

PMID- 22952148
TI  - A critique of methods to measure cytotoxicity in mammalian cell genotoxicity
      assays.
AB  - Various methods have been used to estimate cytotoxicity in mammalian cell
      genotoxicity assays since their introduction more than four decades ago, and
      although there is no agreement on whether any single method is optimal, there is
      now a better appreciation of their limitations. Methods based on aspects of
      cellular function are inevitably inaccurate unless some estimate of cell number
      is included, and those using some measure of cell proliferation give different
      results depending on the mathematical model used. Although it would be desirable,
      it is not possible to provide a universal measure of cytotoxicity because the
      phenomenon is so complex. There is some flexibility in the limits of cytotoxicity
      proposed in regulatory guidelines, and it can be argued these could be even less
      precise. Also, to make valid comparisons of the performance of different test
      systems, novel or established, it would seem essential to use similar measures of
      cytotoxicity.

PMID- 22952149
TI  - Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer
      susceptibility and phenotype.
AB  - Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that
      play a key role in protecting against cancer by detoxifying numerous potentially
      cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes
      GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been
      considered important modifiers of the individual risk for environmentally induced
      cancers such as gastric cancer (GC). However, results are inconsistent among
      studies from different geographic areas and ethnic groups. Our goal was to
      perform a nationwide, case-control study in Spain to evaluate the relevance of
      several functional GST gene polymorphisms and environmental factors to GC risk
      and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy
      controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two
      SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction
      restriction fragment length polymorphism methods. Logistic regression analysis
      identified Helicobacter pylori infection with CagA strains [odds ratio (OR):
      2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI:
      1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent
      risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null
      genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1:
      21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1
      null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in
      HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and
      GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC
      patients and controls. Subgroup analysis for age, gender, Helicobacter pylori
      status, smoking habits, family history of GC, anatomic location and histological
      subtype revealed no significant association between GST variants and GC risk. Our
      results show that the GST polymorphisms evaluated in this study are not relevant
      when determining the individual susceptibility to GC or phenotype in a South
      European population.

PMID- 22952150
TI  - Effects of spindle poisons in peripheral human lymphocytes by the in vitro
      cytokinesis-block micronucleus assay.
AB  - The search for micronuclei (MN) in binucleated cells is not always the best
      choice to recognize microtubule-perturbing agents, as they give rise to
      (micronucleated) mononucleated cells, mainly via mitotic slippage. We therefore
      treated peripheral lymphocytes with vincristine (VCR), nocodazole (NOC) and
      colcemid (COL): (i) to quantify the formation of MN in mononucleated cells and
      the occurrence of abnormal mitoses (c-anaphases, endoreduplicated or tetraploid
      metaphases); (ii) to investigate the role of cytokinesis inhibition in
      determining or modulating the cytogenetic effects induced by the spindle poisons
      (we used either cytochalasin B (cyt B) or latrunculin A, a cytokinesis inhibitor
      that acts differently as compared with cyt B); (iii) to assess the ploidy of
      cells bearing MN by fluorescence in situ hybridisation (FISH) analysis; and (iv)
      to evaluate the levels of the mitotic arrest deficient (MAD2) protein, that
      blocks the cell at the metaphase-anaphase transition, by immunoblotting. We
      observed the induction of numerous abnormal mitoses and tetraploid interphase
      nuclei, as well as of MN in mononucleated cells, a high percentage of which had a
      diploid complement. We also found that the effects were generally not dose but
      chemical dependent, where NOC was proven to be more effective than COL and VCR in
      inducing overall MN formation and, specifically, diploid micronucleated
      lymphocytes. Aneugens damaged cells to a greater extent in the presence of
      cytokinesis inhibitors rather than in their absence. MAD2 protein was expressed
      in controls to an extent reflecting the amount of lymphocytes which were
      initially in the G2/M transition phase. The same trend was seen in aneugen
      treated cells where MAD2 levels decreased with increasing spindle poison
      concentration. Here, we demonstrate that micronucleated mononucleated cells and
      aberrant mitoses can be considered useful markers of exposure to aneugens-like
      spindle poisons causing preferentially, but not exclusively, mitotic slippage.
      Assessment of MAD2 levels can be used to confirm the cell-damaging activity of
      the compounds.

PMID- 22952151
TI  - The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms with
      cancer risk: a meta-analysis of 32 studies.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules, which act as post
      transcriptional regulators of gene expression and have been implicated in
      initiation, progression and treatment outcome of diverse cancers. Single
      nucleotide polymorphisms (SNPs), as the most common type of genetic variation,
      also exist in miRNA genes and can lead to alteration in miRNA expression
      resulting in diverse functional consequences. Emerging studies have evaluated the
      association of miRNA SNPs with cancer risk, but the results remain inconclusive.
      To assess the relationship between miRNA SNPs and cancer risk, we performed a
      meta-analysis of 18 studies involving 20660 subjects for miR-146a rs2910164
      polymorphism and 21 studies involving 26,018 subjects for miR-196a2 rs11614913
      polymorphism. As for rs2910164, no significant association of cancer risk was
      found in the overall analysis. In subgroup analysis by cancer type, ethnicity,
      source of controls and sample size, significant association of cancer risk was
      mainly found in papillary thyroid carcinoma, primary liver cancer, cervical
      cancer, Caucasian population and small sample size studies. For rs11614913,
      significant results were found in all the tested genetic models and T allele or
      its carriers were associated with decreased cancer risk in overall analysis (T
      vs. C: OR = 0.888, 95% CI 0.84-0.938; TT+TC vs. CC: OR = 0.897, 95% CI 0.828
      0.971). In stratified analysis by cancer type and ethnicity, significant
      association of cancer risk was observed in breast cancer, lung cancer, colorectal
      cancer and Asian population, but not in Caucasian population. During further
      stratified analysis by source of controls and sample size, results similar to
      those of overall analysis were found in all of the subgroups. Taken together, our
      results indicated that miR-196a2 rs11614913 T variant probably contribute to
      decreased susceptibility to cancer. However, limited evidence was found for
      association of miR-146a rs2910164 with cancer risk, and further well-designed
      studies with large sample size will be necessary to validate the effect of miR
      146a rs2910164 on cancer susceptibility.

PMID- 22952152
TI  - Prognostic significance of the IASLC/ATS/ERS classification in Chinese patients-A
      single institution retrospective study of 292 lung adenocarcinoma.
AB  - BACKGROUND: A new classification of pulmonary adenocarcinoma has been recently
      proposed by the International Association for the Study of Lung Cancer, American
      Thoracic Society and European Respiratory Society (IASLC/ATS/ERS). This study was
      undertaken in an attempt to explore the clinical implication of this new
      classification in Chinese patients. METHODS: Two hundred ninety-two lung
      adenocarcinomas were reclassified strictly according to the IASLC/ATS/ERS
      classification by two pathologists, independently. Kaplan-Meier and Cox
      regression analyses were used to analyze the correlation between the new
      classification and patients' prognosis. RESULTS: We confirmed three groups with
      different outcomes. Both AIS and MIA had 100% 5-year disease-free survival rate
      and 100% 5-year overall survival rate. Lepidic, acinar, and papillary as well as
      variants of invasive adenocarcinoma had intermediate prognosis. Solid and
      micropapillary cases had poor prognosis (DFS: P < 0.001, OS: P = 0.002). After
      controlling the clinicopathological factors, the new classification was
      identified as an independent prognostic factor in patients' disease-free survival
      and overall survival. CONCLUSIONS: We have demonstrated a valuable prognostic
      role of the new classification in Chinese patients. This new classification is
      valuable of screening out patients with high risk of recurrence to receive
      postoperative adjuvant therapy.

PMID- 22952153
TI  - Analysis of a force system for upper molar distalization using a trans-palatal
      arch and mini-implant: a finite element analysis study.
AB  - The purpose of this study was to analyse distal movements of molars in a force
      system using a trans-palatal arch (TPA), fixed to the maxillary first molar, and
      mini-implants placed at the palatal midline, considering the diagnostic standard
      for placement site in association with variation in upper molar locations, using
      finite element (FE) analysis. Three-dimensional FE models, divided by the
      differing direction of traction force, mesiodistal locations of the left and
      right molars, and the lateral location of the mini-implant were constructed. (1)
      When a traction force was fixed from the height of alveolar crest to the mini
      implant placed at the middle of palate, the molars underwent bodily movement. (2)
      When the location of the mini-implant was moved to the left of the midline, the
      amount of distal movement of the left molar increased. When the mesiodistal
      locations of the left and right molars differed, the amount of distal movement of
      the molar located mesially was larger than that of the contralateral molar, even
      when the mini-implant was located on the midline. 

PMID- 22952154
TI  - Effect of immediate loading on the biomechanical properties of bone surrounding
      the miniscrew implants.
AB  - The aim of this study was to investigate the effect of immediate loading on the
      biomechanical properties of bone surrounding a miniscrew implant. Forty titanium
      alloy miniscrew implants were placed on the buccal side of the maxillae and
      mandibles in four beagle dogs. Twelve pairs of miniscrew implants were
      immediately loaded with approximately 150 g of continuous force using nickel
      titanium coil springs and the remaining 16 implants were left unloaded for 8
      weeks. Nanoindentation testing was performed (peak load 10 mN) and the hardness
      and elastic modulus were calculated. Two series of indentations (in cortical and
      trabecular bone) for both the compression and tension sides were made. For each
      site, five indentations were placed approximately 25 MUm from the implant-bone
      interface and 250 MUm from the screw thread. The mean hardness and elastic
      modulus were generally higher in mandibles than maxillae and were higher in
      cortical bone than in trabecular bone. The trabecular bone near the implant-bone
      interface on the compression side was significantly harder than that at other
      locations in trabecular bone. In conclusion, this is the first study that has
      investigated the biomechanical properties of bone surrounding a miniscrew implant
      under immediate loading using nanoindentation testing. The mechanical properties
      of bone surrounding a miniscrew implant may be influenced by immediate loading.

PMID- 22952155
TI  - Cautious use of thread shape factor.

PMID- 22952157
TI  - Survival of patients operated for colorectal liver metastases and concomitant
      extra-hepatic disease: external validation of a prognostic model.
AB  - BACKGROUND: The presence of extra-hepatic disease (EHD) is no longer an absolute
      contraindication to surgery in patients with colorectal liver metastases (CRLM).
      Recently, a novel prognostic model predicting overall survival in such patients
      was proposed using five risk factors (EHD other than isolated lung metastases,
      CEA >=10 ng/ml, >5 liver metastases, right colon as the primary CRC location, and
      diagnosis of EHD concomitant to CRLM recurrence). A bi-institutional database was
      used to perform an external validation of this model. METHODS: Ninety-seven
      patients operated for CRLM and EHD between 1982 and 2011 in two institutions was
      analyzed. The proposed prognostic model was validated in this cohort using Cox
      proportional hazards models and the concordance index (c). RESULTS: Of the five
      proposed risk factors, only EHD other than isolated lung metastases was found to
      independently predict overall survival [Hazards Ratio (HR) = 2.10 (95% CI: 1.01
      4.40)]. Although, the number of risk factors was marginally associated with
      overall survival in univariate analysis (P = 0.049), the performance of the
      proposed prognostic model was poor when applied to our cohort (c = 0.64).
      CONCLUSION: The examined prognostic model of survival in patients with CRLM and
      EHD had poor performance. Further research is warranted to delineate the subset
      of patients who will benefit from surgery.

PMID- 22952158
TI  - Quantifying RNA-protein interactions in situ using modified-MTRIPs and proximity
      ligation.
AB  - The stabilization, translation and degradation of RNA are regulated by
      interactions between trans-acting factors, such as microRNA and RNA-binding
      proteins (RBP). In order to investigate the relationships between these events
      and their significance, a method that detects the localization of these
      interactions within a single cell, as well as their variability across a cell
      population, is needed. To visualize and quantify RNA-protein interactions in
      situ, we developed a proximity ligation assay (PLA) that combined peptide
      modified, multiply-labelled tetravalent RNA imaging probes (MTRIPs), targeted to
      sequences near RBP binding sites, with proximity ligation and rolling circle
      amplification (RCA). Using this method, we detected and quantified, with single
      interaction sensitivity, the localization and frequency of interactions of the
      human respiratory syncytial virus (hRSV) nucleocapsid protein (N) with viral
      genomic RNA (gRNA). We also described the effects of actinomycin D (actD) on the
      interactions of HuR with beta-actin mRNA and with poly(A)+ mRNA at both native
      and increased HuR expression levels.

PMID- 22952159
TI  - Transferring responsibility and accountability in maternity care: clinicians
      defining their boundaries of practice in relation to clinical handover.
AB  - OBJECTIVE: This exploratory study reports on maternity clinicians' perceptions of
      transfer of their responsibility and accountability for patients in relation to
      clinical handover with particular focus transfers of care in birth suite. DESIGN:
      A qualitative study of semistructured interviews and focus groups of maternity
      clinicians was undertaken in 2007. De-indentified data were transcribed and coded
      using the constant comparative method. Multiple themes emerged but only those
      related to responsibility and accountability are reported in this paper. SETTING:
      One tertiary Australian maternity hospital. PARTICIPANTS: Maternity care
      midwives, nurses (neonatal, mental health, bed managers) and doctors (obstetric,
      neontatology, anaesthetics, internal medicine, psychiatry). PRIMARY OUTCOME
      MEASURES: Primary outcome measures were the perceptions of clinicians of
      maternity clinical handover. RESULTS: The majority of participants did not
      automatically connect maternity handover with the transfer of responsibility and
      accountability. Once introduced to this concept, they agreed that it was one of
      the roles of clinical handover. They spoke of complete transfer, shared and
      ongoing responsibility and accountability. When clinicians had direct involvement
      or extensive clinical knowledge of the patient, blurring of transition of
      responsibility and accountability sometimes occurred. A lack of 'ownership' of a
      patient and their problems were seen to result in confusion about who was to
      address the clinical issues of the patient. Personal choice of ongoing
      responsibility and accountability past the handover communication were described.
      This enabled the off-going person to rectify an inadequate handover or assist in
      an emergency when duty clinicians were unavailable. CONCLUSIONS: There is a clear
      lack of consensus about the transition of responsibility and accountability-this
      should be explicit at the handover. It is important that on each shift and new
      workplace environment clinicians agree upon primary role definitions,
      responsibilities and accountabilities for patients. To provide system resilience,
      secondary responsibilities may be allocated as required.

PMID- 22952160
TI  - Patterns in wireless phone estimation data from a cross-sectional survey: what
      are the implications for epidemiology?
AB  - OBJECTIVE: Self-reported recall data are often used in wireless phone
      epidemiological studies, which in turn are used to indicate relative risk of
      health outcomes from extended radiofrequency exposure. We sought to explain
      features commonly observed in wireless phone recall data and to improve
      analytical procedures. SETTING: Wellington Region, New Zealand. PARTICIPANTS:
      Each of the 16 schools selected a year 7 and/or 8 class to participate, providing
      a representative regional sample based on socioeconomic school ratings, school
      type and urban/rural balance. There was an 85% participation rate (N=373). MAIN
      OUTCOME MEASURES: Planned: the distribution of participants' estimated extent of
      SMS-texting and cordless phone calls, and the extent of rounding to a final zero
      or five within the full set of recall data and within each order of magnitude.
      Unplanned: the distribution of the leading digits of these raw data, compared
      with that of billed data in each order of magnitude. RESULTS: The nature and
      extent of number-rounding, and the distribution of data across each order in
      recall data indicated a logarithmic (ratio-based) mental process for assigning
      values. Responses became less specific as the leading-digit increased from 1 to
      9, and 69% of responses for weekly texts sent were rounded by participants to a
      single non-zero digit (eg, 2, 20 and 200). CONCLUSIONS: Adolescents' estimation
      of their cellphone use indicated that it was performed on a mental logarithmic
      scale. This is the first time this phenomenon has been observed in the estimation
      of recalled, as opposed to observed, numerical quantities. Our findings provide
      empirical justification for log-transforming data for analysis. We recommend the
      use of the geometric rather than arithmetic mean when a recalled numerical range
      is provided. A point of calibration may improve recall.

PMID- 22952161
TI  - Jurisdictional, socioeconomic and gender inequalities in child health and
      development: analysis of a national census of 5-year-olds in Australia.
AB  - OBJECTIVES: Early child development may have important consequences for
      inequalities in health and well-being. This paper explores population level
      patterns of child development across Australian jurisdictions, considering
      socioeconomic and demographic characteristics. DESIGN: Census of child
      development across Australia. SETTING AND PARTICIPANTS: Teachers complete a
      developmental checklist, the Australian Early Development Index (AEDI), for all
      children in their first year of full-time schooling. Between May and July 2009,
      the AEDI was collected by 14 628 teachers in primary schools (government and non
      government) across Australia, providing information on 261 147 children
      (approximately 97.5% of the estimated 5-year-old population). OUTCOME MEASURES:
      Level of developmental vulnerability in Australian children for five
      developmental domains: physical well-being, social competence, emotional
      maturity, language and cognitive skills and communication skills and general
      knowledge. RESULTS: The results show demographic and socioeconomic inequalities
      in child development as well as within and between jurisdiction inequalities. The
      magnitude of the overall level of inequality in child development and the impact
      of covariates varies considerably both between and within jurisdiction by sex.
      For example, the difference in overall developmental vulnerability between the
      best-performing and worst-performing jurisdiction is 12.5% for males and 7.1% for
      females. Levels of absolute social inequality within jurisdictions range from
      8.2% for females to 12.7% for males. CONCLUSIONS: The different mix of universal
      and targeted services provided within jurisdictions from pregnancy to age 5 may
      contribute to inequality across the country. These results illustrate the
      potential utility of a developmental census to shed light on the impact of
      differences in universal and targeted services to support child development by
      school entry.

PMID- 22952162
TI  - Effect of stamped reply envelopes and timing of newsletter delivery on response
      rates of mail survey: a randomised controlled trial in a prospective cohort
      study.
AB  - OBJECTIVE: To examine the effects of stamped reply envelope and the timing of
      newsletter distribution. DESIGN: A randomised controlled trial in a prospective
      cohort study with a 2*2 factorial design of two interventions. SETTING: The Japan
      Nurses' Health Study (JNHS), a prospective cohort study for women's health.
      PARTICIPANTS: The present study included 6938 women who were part of the first
      year entry cohort for the fifth wave of the biannual follow-up survey of the
      JNHS. INTERVENTION: The participants were randomly allocated into four groups;
      Group-1 (business-reply, newsletter with initial mailing), Group-2 (business
      reply, newsletter with reminder), Group-3 (stamped envelopes, newsletter with
      initial mailing) and Group-4 (stamped envelopes, newsletter with reminder). The
      thank-you and reminder letters were mailed out at the end of the sixth week. This
      study was censored at the end of 12 weeks. MAIN OUTCOME MEASURES: Main outcome
      measures were cumulative response at the end of 6 and 12 weeks after mailing out
      the questionnaire. RESULTS: The cumulative response at 12 weeks were 58.3% for
      Group-1, 54.1% for Group-2, 60.5% for Group-3 and 56.7% for Group-4 (p=0.001).
      The odds of the response was higher for stamped envelopes than for business-reply
      envelopes (OR (95% CI)=1.10(1.00 to 1.21)). The odds was higher for newsletter
      delivery with initial mailing than for with reminder (1.18(1.07 to 1.29)). The
      response in first 6 weeks for stamped envelope was significantly higher than for
      business-reply envelope (p=0.047). Although the response in 6 weeks for women
      received the newsletter with initial mailing was lower than for women who did
      not, the proportions did not differ significantly (p=0.291). CONCLUSIONS: The
      style of return envelope affected response rates of mail survey. The results of
      this study suggest that practices of provision of the additional information,
      should be handled individually in advance, as a separate event from sending
      follow-up questionnaire or reminder letters.

PMID- 22952163
TI  - Carers' perspectives on the presentation of community-acquired pneumonia and
      empyema in children: a case series.
AB  - OBJECTIVE: To describe carers' perceptions of the development and presentation of
      community-acquired pneumonia or empyema in their children. DESIGN: Case series.
      SETTING: Seven hospitals with paediatric inpatient units in South Wales, UK.
      PARTICIPANTS: Carers of 79 children aged 6 months to 16 years assessed in
      hospital between October 2008 and September 2009 with radiographic, community
      acquired pneumonia or empyema. METHODS: Carers were recruited in hospital and
      participated in a structured face-to-face or telephone interview about the
      history and presenting features of their children's illnesses. Responses to open
      questions were initially coded very finely and then grouped into common themes.
      Cases were classified into two age groups: 3 or more years and under 3 years.
      RESULTS: The reported median duration of illness from onset until the index
      hospital presentation was 4 days (IQR 2-9 days). Pain in the torso was reported
      in 84% of cases aged 3 or more years and was the most common cause for carer
      concern in this age group. According to carer accounts, clinicians sometimes
      misjudged the origin of this pain. Almost all carers reported something unusual
      about the index illness that had particularly concerned them-mostly non-specific
      physical symptoms and behavioural changes. CONCLUSIONS: Pain in the torso and
      carer concerns about unusual symptoms in their child may provide valuable
      additional information in a clinician's assessment of the risk of pneumonia in
      primary care. Further research is needed to confirm the diagnostic value of these
      features.

PMID- 22952164
TI  - Public perceptions of coronary events risk factors: a discrete choice experiment.
AB  - OBJECTIVES: To assess public perceptions of coronary heart disease (CHD) risk
      factors. DESIGN: Discrete choice experiment questionnaire. SETTING: Six
      provincial centres in Northern Ireland. PARTICIPANTS: 1000 adults of the general
      public in Northern Ireland. PRIMARY AND SECONDARY OUTCOMES: The general public's
      perception of CHD risk factors. The effect of having risk factor(s) on that
      perception. RESULTS: Two multinomial logit models were created. One was a basic
      model (no heterogeneity permitted), while the other permitted heterogeneity based
      on respondents' characteristics. In both models individuals with very high
      cholesterol were perceived to be at the highest risk of having a coronary event.
      Respondents who reported having high cholesterol perceived the risk contribution
      of very high cholesterol to be greater than those who reported having normal
      cholesterol. Similar findings were observed with blood pressure and smoking.
      Respondents who were male and older perceived the contribution of age and gender
      to be lower than respondents who were female and younger. CONCLUSIONS:
      Respondents with different risk factors perceived such factors differently. These
      divergent perceptions of CHD risk factors could be a barrier to behavioural
      change. This brings into focus the need for more tailored health promotion
      campaigns to tackle CHD.

PMID- 22952166
TI  - Pathways to a rising caesarean section rate: a population-based cohort study.
AB  - OBJECTIVES: To determine whether the obstetric pathways leading to caesarean
      section changed from one decade to another. We also aimed to explore how much of
      the increase in caesarean rate could be attributed to maternal and pregnancy
      factors including a shift towards delivery in private hospitals. DESIGN:
      Population-based record linkage cohort study. SETTING: New South Wales,
      Australia. PARTICIPANTS: For annual rates, all women giving birth in NSW during
      1994 to 2009 were included. To examine changes in obstetric pathways two cohorts
      were compared: all women with a first-birth during either 1994-1997 (82 988
      women) or 2001-2004 (85 859 women) and who had a second (sequential) birth within
      5 years of their first-birth. PRIMARY OUTCOME MEASURES: Caesarean section rates,
      by parity and onset of labour. RESULTS: For first-births, prelabour and
      intrapartum caesarean rates increased from 1994 to 2009, with intrapartum rates
      rising from 6.5% to 11.7%. This fed into repeat caesarean rates; from 2003, over
      18% of all multiparous births were prelabour repeat caesareans. In the 1994-1997
      cohort, 17.7% of women had a caesarean delivery for their first-birth. For their
      second birth, the vaginal birth after caesarean (VBAC) rate was 28%. In the 2001
      2004 cohort, 26.1% of women had a caesarean delivery for their first-birth and
      the VBAC rate was 16%. Among women with a first-birth, maternal and pregnancy
      factors and increasing deliveries in private hospitals, only explained 24% of the
      rise in caesarean rates from 1994 to 2009. CONCLUSIONS: Rising first-birth
      caesarean rates drove the overall increase. Maternal factors and changes in
      public/private care could explain only a quarter of the increase. Changes in the
      perceived risks of vaginal birth versus caesarean delivery may be influencing the
      pregnancy management decisions of clinicians and/or mothers.

PMID- 22952165
TI  - Lung Injury Prevention with Aspirin (LIPS-A): a protocol for a multicentre
      randomised clinical trial in medical patients at high risk of acute lung injury.
AB  - INTRODUCTION: Acute lung injury (ALI) is a devastating condition that places a
      heavy burden on public health resources. Although the need for effective ALI
      prevention strategies is increasingly recognised, no effective preventative
      strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to
      test whether aspirin (ASA) could prevent and/or mitigate the development of ALI.
      METHODS AND ANALYSIS: LIPS-A is a multicentre, double-blind, randomised clinical
      trial testing the hypothesis that the early administration of ASA will result in
      a reduced incidence of ALI in adult patients at high risk. This investigation
      will enrol 400 study participants from 14 hospitals across the USA. Conditional
      logistic regression will be used to test the primary hypothesis that early ASA
      administration will decrease the incidence of ALI. ETHICS AND DISSEMINATION:
      Safety oversight will be under the direction of an independent Data and Safety
      Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB
      prior to enrolling the first study participant. Approval of both the protocol and
      informed consent documents were also obtained from the institutional review board
      of each participating institution prior to enrolling study participants at the
      respective site. In addition to providing important clinical and mechanistic
      information, this investigation will inform the scientific merit and feasibility
      of a phase III trial on ASA as an ALI prevention agent. The findings of this
      investigation, as well as associated ancillary studies, will be disseminated in
      the form of oral and abstract presentations at major national and international
      medical specialty meetings. The primary objective and other significant findings
      will also be presented in manuscript form. All final, published manuscripts
      resulting from this protocol will be submitted to Pub Med Central in accordance
      with the National Institute of Health Public Access Policy.

PMID- 22952167
TI  - Sustainable nitrogen fertilisation in sweet pepper: assessing growth and fruit
      quality and the potential nitrate pollution from different organic manures.
AB  - BACKGROUND: The use of organic cultivation with manures does not avoid the risk
      of high nitrate concentrations if nutrient management is inefficient. So we
      studied the influence of three organic manures combined or not with additional
      chemical fertilisers on growth and yield of sweet pepper (Capsicum annuum L.),
      and on the soil and plant N concentrations. RESULTS: After 3 years of organic
      cultivation, poultry manure caused the highest soil pollution. The evolution of
      nitrate and organic matter in soil showed a pattern close to that of plant
      growth. The addition of mineral fertiliser increased vegetative growth and yield,
      and a cumulative season effect was observed. In treatments with no additional
      mineral fertiliser N translocation from leaves to fruits happened. A cumulative
      effect of seasons on fruit quality and a reduction near to 30% was observed in
      the first fruit quality category after 3 years. The fruit vitamin C content was
      reduced by increasing N fertilisation. CONCLUSION: The effects of organic
      fertiliser on soil and plant growth and yield depended on the type of manure
      used, its rate, and consecutive crop seasons. Horse manure gave the best
      combination of agricultural and environmental characteristics and could be used
      without additional fertigation.

PMID- 22952168
TI  - Crystal engineering of a microporous, catalytically active fcu topology MOF using
      a custom-designed metalloporphyrin linker.

PMID- 22952169
TI  - Role of microparticles in sepsis.
AB  - This review discusses the role of microparticles in inflammation, coagulation,
      vascular function, and most importantly, their physiological and pathological
      functions in sepsis. Microparticles are proinflammatory, procoagulant membrane
      vesicles released from various cell types. They are detectable in normal
      individuals and basal levels correlate with a balance between cell proliferation,
      stimulation, and destruction. Haemostatic imbalance leads to various pathological
      states of inflammation and thrombosis including cardiovascular disease and
      sepsis, where circulating microparticles display both an increase in number and
      phenotypic change. Microparticles, mainly of platelet origin enable both local
      and disseminated amplification of the haemostatic response to endothelial injury
      through exposure of phosphatidylserine, tissue factor, and coagulation factor
      binding sites. Surface expression of membrane antigens by microparticles
      facilitates cytoadhesion, chemotaxis, and cytokine secretion to drive a
      proinflammatory response. Microparticles behave as vectors in the transcellular
      exchange of biological information and are important regulators of endothelial
      function and angiogenesis. The extent to which circulating microparticles
      contribute to the pathogenesis of sepsis and disseminated intravascular
      coagulation is currently unknown. Microparticles may in fact be beneficial in
      early sepsis, given that activated protein C bound to endothelium-derived
      microparticles retains anticoagulant activity, and increased circulating
      microparticles are protective against vascular hyporeactivity. Elevated levels of
      microparticles in early sepsis may therefore compensate for the host's systemic
      inflammatory response. Importantly, in vivo, septic microparticles induce
      deleterious changes in the expression of enzyme systems related to inflammation
      and oxidative stress, thus they may represent important contributors to multi
      organ failure in septic shock.

PMID- 22952170
TI  - Effect of eugenol and guaiacol application on tomato aroma composition determined
      by headspace stir bar sorptive extraction.
AB  - BACKGROUND: The present work was carried out because there is only a small amount
      of literature on how the volatile composition of tomatoes can be modified by the
      effect of exogenous substances in contact with tomato plants. This work studies
      how eugenol and guaiacol, either by foliar application and/or in the surrounding
      atmosphere, can affect the volatile composition of this fruit. An important work
      of this study was also conduced to validate the analytical method [headspace stir
      bar sorptive extraction-gas chromatography-mass spectrometry (HS-SBSE-GC-MS)] to
      determine the composition of the volatiles in tomato. RESULTS: Analytical method
      validation parameters such as linearity, limit of detection, limit of
      quantification, and recovery proved that this method is suitable for the analysis
      of tomato volatiles. Their eugenol and guaiacol content changed, with an increase
      of 200 and 35 times, respectively, when foliar treatment was used, and an
      increase of 10, in both cases, when plants were in contact with the contaminated
      atmosphere. As consequence of the treatments other volatile compounds changed
      considerably. CONCLUSION: For first time, a HS-SBSE-GC-MS method was successfully
      validated for the study of volatiles in tomatos. Results suggests that exogenous
      compounds in contact with the plants, such as eugenol and guaiacol, can be
      absorbed changing the global volatile composition of fruits, which could produce
      a negative or positive effect in their aroma.

PMID- 22952171
TI  - Urinary alpha-carboxyethyl hydroxychroman can be used as a predictor of alpha
      tocopherol adequacy, as demonstrated in the Energetics Study.
AB  - BACKGROUND: Other than the in vitro erythrocyte hemolysis test, no valid
      biomarkers of vitamin E status currently exist. OBJECTIVE: We hypothesized that
      the urinary vitamin E metabolite alpha-carboxyethyl hydroxychroman (alpha-CEHC)
      could serve as a biomarker. DESIGN: The relations between urinary alpha-CEHC,
      plasma alpha-tocopherol, and vitamin E intakes were assessed by using a
      previously validated multipass, Web-based, 24-h self-administered dietary recall,
      and we concurrently collected plasma and 24-h urine samples from 233 participants
      of both sexes. RESULTS: Median vitamin E intakes were 9.7 mg alpha-tocopherol/d.
      Intakes were correlated with plasma alpha-tocopherol (R = 0.40, P < 0.001) and
      urinary alpha-CEHC (R = 0.42, P < 0.001); these correlations were essentially
      unchanged after multivariate adjustments. On the basis of multiple regression
      analysis, urinary alpha-CEHC excretion increased by ~0.086 MUmol/g creatinine
      (95% CI: 0.047, 0.125) for every 1-mg (2.3-MUmol) increase in dietary alpha
      tocopherol. Urinary alpha-CEHC excretion remained at a plateau (median: 1.39
      MUmol/g creatinine) until dietary intakes of alpha-tocopherol exceeded 9 mg alpha
      tocopherol/d. The inflection point at which vitamin E metabolism increased was
      estimated to be at an intake of 12.8 mg alpha-tocopherol/d. Daily excretion of
      >1.39 MUmol alpha-CEHC/g creatinine is associated with a greater than adequate
      alpha-tocopherol status, as evidenced by increased vitamin E metabolism and
      excretion. CONCLUSION: Thus, urinary alpha-CEHC is a valid biomarker of alpha
      tocopherol status that can be used to set a value for the Estimated Adequate
      Requirement of vitamin E.

PMID- 22952172
TI  - Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy
      and Roux-en-Y gastric bypass in morbidly obese women.
AB  - BACKGROUND: The effect of bariatric surgery on iron absorption is only partially
      known. OBJECTIVE: The objective was to study the effects of sleeve gastrectomy
      (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption
      and iron status. DESIGN: Fifty-eight menstruating women were enrolled in this
      prospective study [mean (+/-SD) age: 35.9 +/- 9.1 y; weight: 101.7 +/- 13.5 kg;
      BMI (in kg/m2): 39.9 +/- 4.4]. Anthropometric, body-composition, dietary, and
      hematologic indexes and heme- and nonheme-iron absorption-using a standardized
      meal containing 3 mg Fe-were determined before and 12 mo after surgery. Forty
      three subjects completed the 12-mo follow-up. Iron supplements were strictly
      controlled. RESULTS: Heme-iron absorption was 23.9% before and 6.2% 12 mo after
      surgery (P < 0.0001). Nonheme-iron absorption decreased from 11.1% to 4.7% (P <
      0.0001). No differences were observed by type of surgery. Iron intakes from all
      sources of supplements were 27.9 +/- 6.2 mg/d in the SG group and 63.2 +/- 21.1
      mg/d in the RYGBP group (P < 0.001). Serum ferritin and total-body iron decreased
      more after RYGBP than after SG. CONCLUSIONS: Iron (heme and nonheme) absorption
      is markedly reduced after SG and RYGBP. The magnitude of the decrease in heme
      iron absorption is greater than that of nonheme iron. The amounts suggested as
      iron supplements may need to be increased to effectively prevent iron-status
      impairment.

PMID- 22952173
TI  - Role of dairy foods in weight management.

PMID- 22952174
TI  - Choline intake and risk of lethal prostate cancer: incidence and survival.
AB  - BACKGROUND: Meat, milk, and eggs have been inconsistently associated with the
      risk of advanced prostate cancer. These foods are sources of choline-a nutrient
      that may affect prostate cancer progression through cell membrane function and
      one-carbon metabolism. No study has examined dietary choline and the risk of
      lethal prostate cancer. OBJECTIVE: Our objective was to examine whether dietary
      choline, choline-containing compounds, and betaine (a choline metabolite)
      increase the risk of lethal prostate cancer. DESIGN: We prospectively examined
      the intake of these nutrients and the risk of lethal prostate cancer among 47,896
      men in the Health Professionals Follow-Up Study. In a case-only survival
      analysis, we examined the postdiagnostic intake of these nutrients and the risk
      of lethal prostate cancer among 4282 men with an initial diagnosis of
      nonmetastatic disease during follow-up. Diet was assessed with a validated
      questionnaire 6 times during 22 y of follow-up. RESULTS: In the incidence
      analysis, we observed 695 lethal prostate cancers during 879,627 person-years.
      Men in the highest quintile of choline intake had a 70% increased risk of lethal
      prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only
      survival analysis, we observed 271 lethal cases during 33,679 person-years.
      Postdiagnostic choline intake was not statistically significantly associated with
      the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1:
      1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). CONCLUSION: Of the 47,896 men in our
      study population, choline intake was associated with an increased risk of lethal
      prostate cancer.

PMID- 22952175
TI  - Treatment of moderate acute malnutrition with ready-to-use supplementary food
      results in higher overall recovery rates compared with a corn-soya blend in
      children in southern Ethiopia: an operations research trial.
AB  - BACKGROUND: Moderate and severe acute malnutrition affects 13% of children <5 y
      of age worldwide. Severe acute malnutrition affects fewer children but is
      associated with higher rates of mortality and morbidity. Supplementary feeding
      programs aim to treat moderate acute malnutrition and prevent the deterioration
      to severe acute malnutrition. OBJECTIVE: The aim was to compare recovery rates of
      children with moderate acute malnutrition in supplementary feeding programs by
      using the newly recommended ration of ready-to-use supplementary food (RUSF) and
      the more conventional ration of corn-soya blend (CSB) in Ethiopia. DESIGN: A
      total of 1125 children aged 6-60 mo with moderate acute malnutrition received 16
      wk of CSB or RUSF. Children were randomly assigned to receive one or the other
      food. The daily rations were purposely based on the conventional treatment
      rations distributed at the time of the study in Ethiopia: 300 g CSB and 32 g
      vegetable oil in the control group (1413 kcal) and 92 g RUSF in the intervention
      group (500 kcal). The higher ration size of CSB was provided because of expected
      food sharing. RESULTS: The HR for children in the CSB group was 0.85 (95% CI:
      0.73, 0.99), which indicated that they had 15% lower recovery (P = 0.039).
      Recovery rates of children at the end of the 16-wk treatment period trended
      higher in the RUSF group (73%) than in the CSB group (67%) (P = 0.056).
      CONCLUSION: In comparison with CSB, the treatment of moderate acute malnutrition
      with RUSF resulted in higher recovery rates in children, despite the large ration
      size and higher energy content of the conventional CSB ration.

PMID- 22952176
TI  - Randomized controlled trial of meat compared with multimicronutrient-fortified
      cereal in infants and toddlers with high stunting rates in diverse settings.
AB  - BACKGROUND: Improved complementary feeding is cited as a critical factor for
      reducing stunting. Consumption of meats has been advocated, but its efficacy in
      low-resource settings has not been tested. OBJECTIVE: The objective was to test
      the hypothesis that daily intake of 30 to 45 g meat from 6 to 18 mo of age would
      result in greater linear growth velocity and improved micronutrient status in
      comparison with an equicaloric multimicronutrient-fortified cereal. DESIGN: This
      was a cluster randomized efficacy trial conducted in the Democratic Republic of
      Congo, Zambia, Guatemala, and Pakistan. Individual daily portions of study foods
      and education messages to enhance complementary feeding were delivered to
      participants. Blood tests were obtained at trial completion. RESULTS: A total of
      532 (86.1%) and 530 (85.8%) participants from the meat and cereal arms,
      respectively, completed the study. Linear growth velocity did not differ between
      treatment groups: 1.00 (95% CI: 0.99, 1.02) and 1.02 (95% CI: 1.00, 1.04) cm/mo
      for the meat and cereal groups, respectively (P = 0.39). From baseline to 18 mo,
      stunting [length-for-age z score (LAZ) <-2.0] rates increased from ~33% to nearly
      50%. Years of maternal education and maternal height were positively associated
      with linear growth velocity (P = 0.0006 and 0.003, respectively); LAZ at 6 mo was
      negatively associated (P < 0.0001). Anemia rates did not differ by group; iron
      deficiency was significantly lower in the cereal group. CONCLUSION: The high rate
      of stunting at baseline and the lack of effect of either the meat or multiple
      micronutrient-fortified cereal intervention to reverse its progression argue for
      multifaceted interventions beginning in the pre- and early postnatal periods.

PMID- 22952178
TI  - Determination of the tolerable upper intake level of leucine in acute dietary
      studies in young men.
AB  - BACKGROUND: Leucine has been suggested to improve athletic performance.
      Therefore, the branched-chain amino acids (BCAAs), especially leucine, are
      popular as dietary supplements in strength-training athletes; however, the intake
      of leucine in excess of requirements raises concerns regarding adverse effects.
      Currently, the tolerable upper intake level (UL) for leucine is unknown.
      OBJECTIVE: The objective of the current study was to determine the UL for leucine
      in adult men under acute dietary conditions. DESIGN: Five healthy adults (20-35
      y) each received graded stepwise increases in leucine intakes of 50, 150, 250,
      500, 750, 1000, and 1250 mg . kg-1 . d-1, which corresponded to the Estimated
      Average Requirement (EAR) and the EAR *3, *5, *10, *15, *20, and *25 in a total
      of 29 studies. The UL of leucine was identified by the measurement of plasma and
      urinary biochemical variables and changes in leucine oxidation by using l-[1-13C]
      leucine. RESULTS: A significant increase in blood ammonia concentrations above
      normal values, plasma leucine concentrations, and urinary leucine excretion were
      observed with leucine intakes >500 mg . kg-1 . d-1. The oxidation of l-[1-13C]
      leucine expressed as label tracer oxidation in breath (F13CO2), leucine
      oxidation, and alpha-ketoisocaproic acid (KIC) oxidation led to different
      results: a plateau in F13CO2 observed after 500 mg . kg-1 . d-1, no clear plateau
      observed in leucine oxidation, and KIC oxidation appearing to plateau after 750
      mg . kg-1 . d-1. CONCLUSION: On the basis of plasma and urinary variables, the UL
      for leucine in healthy adult men can be suggested at 500 mg . kg-1 . d-1 or ~35
      g/d as a cautious estimate under acute dietary conditions.

PMID- 22952177
TI  - Zinc and heme iron intakes and risk of colorectal cancer: a population-based
      prospective cohort study in Japan.
AB  - BACKGROUND: Food sources and intakes of zinc and heme iron may differ between
      Western and Asian populations. However, all of the studies on the association
      between zinc and heme iron intakes and colorectal cancer have been conducted in
      Western populations. OBJECTIVE: We investigated the association between zinc and
      heme iron intakes and colorectal cancer risk in a Japanese general population.
      DESIGN: We conducted a large, population-based prospective study in 39,721 men
      and 45,376 women aged 45-74 y. Heme iron and zinc intakes were measured by using
      a validated food-frequency questionnaire in either 1995 or 1998. RESULTS: During
      as many as 808,053 person-years of follow-up until the end of 2006, 1284
      colorectal cancer cases were identified. In multivariate-adjusted models, zinc
      and heme iron intakes were not associated with colorectal cancer in either men or
      women. In comparison with the lowest quartile, the HRs (95% CIs) for developing
      colorectal cancer in the fourth quartile of zinc and heme iron intakes were 0.77
      (0.58, 1.03; P-trend = 0.2) and 1.06 (0.79, 1.42; P-trend = 0.6), respectively,
      for men and 1.05 (0.77, 1.44; P-trend = 0.4) and 0.88 (0.61, 1.29; P-trend =
      0.4), respectively, for women. CONCLUSION: Our results in a Japanese population
      with lower intakes and different major food sources of zinc and heme iron in
      comparison with those of Western populations suggest that zinc and heme iron
      intakes are not associated with colorectal cancer.

PMID- 22952179
TI  - Diet and exercise weight-loss trial in lactating overweight and obese women.
AB  - BACKGROUND: Current evidence suggests a combined treatment of postpartum weight
      loss of diet and exercise. However, to our knowledge, neither their separate and
      interactive effects nor long-term outcomes have been evaluated. OBJECTIVE: We
      evaluated whether a 12-wk dietary behavior modification (D) treatment to decrease
      energy intake, physical exercise behavior modification (E) treatment to implement
      moderate aerobic exercise, or combined dietary and physical exercise behavior
      modification (DE) treatment compared with control (usual care) (C) reduces body
      weight in lactating women measured at the end of treatment and at a 1-y follow-up
      9 mo after treatment termination. DESIGN: At 10-14 wk postpartum, 68 lactating
      Swedish women with a prepregnancy BMI (in kg/m2) of 25-35 were randomly assigned
      to D, E, DE, or C groups. Measurements were made at baseline, after the
      intervention, and again at a 1-y follow-up 9 mo later. A 2 * 2 factorial approach
      was used to analyze main and interaction effects of treatments. RESULTS: Weight
      changes after the intervention and 1-y follow-up were -8.3 +/- 4.2 and -10.2 +/-
      5.7 kg, respectively, in the D group; -2.4 +/- 3.2 and -2.7 +/- 5.9 kg,
      respectively, in the E group; -6.9 +/- 3.0 and -7.3 +/- 6.3 kg, respectively, in
      the DE group; and -0.8 +/- 3.0 and -0.9 +/- 6.6 kg, respectively, in the C group.
      The main effects of D treatment, but not of E treatment, on weight were
      significant at both times (P < 0.001). CONCLUSIONS: Dietary treatment provided
      clinically relevant weight loss in lactating postpartum women, which was
      sustained at 9 mo after treatment. The combined treatment did not yield
      significant weight or body-composition changes beyond those of dietary treatment
      alone.

PMID- 22952180
TI  - Effect of short-term carbohydrate overfeeding and long-term weight loss on liver
      fat in overweight humans.
AB  - BACKGROUND: Cross-sectional studies have identified a high intake of simple
      sugars as an important dietary factor predicting nonalcoholic fatty liver disease
      (NAFLD). OBJECTIVE: We examined whether overfeeding overweight subjects with
      simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this
      is reversible by weight loss. DESIGN: Sixteen subjects [BMI (kg/m2): 30.6 +/-
      1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3
      wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped
      for rs739409 in the PNPLA3 gene. Before and after overfeeding and after
      hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic
      resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate
      (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. RESULTS:
      Carbohydrate overfeeding increased weight (+/-SEM) by 2% (1.8 +/- 0.3 kg; P <
      0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL
      increased in proportion to the increase in liver fat and serum triglycerides in
      subjects with PNPLA3-148IIbut not PNPLA3-148MM. During the hypocaloric diet, the
      subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their
      liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). CONCLUSIONS:
      Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in
      liver fat (27%) than in body weight (2%). The increase in liver fat was
      proportional to that in DNL. Weight loss restores liver fat to normal. These data
      indicate that the human fatty liver avidly accumulates fat during carbohydrate
      overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial
      was registered at www.hus.fi as 235780.

PMID- 22952181
TI  - Novel metabolites and roles for alpha-tocopherol in humans and mice discovered by
      mass spectrometry-based metabolomics.
AB  - BACKGROUND: Contradictory results from clinical trials that examined the role of
      vitamin E in chronic disease could be a consequence of interindividual variation,
      caused by factors such as xenobiotic use. Cometabolism of vitamin E with other
      pharmaceutical products could affect the bioavailability of the drug. Thus, it is
      necessary to understand fully the metabolic routes and biological endpoints of
      vitamin E. OBJECTIVE: The objective was to uncover novel metabolites and roles of
      vitamin E in humans and mouse models. DESIGN: Human volunteers (n = 10) were fed
      almonds for 7 d and then an alpha-tocopherol dietary supplement for 14 d. Urine
      and serum samples were collected before and after dosing. C57BL/6 mice (n = 10)
      were also fed alpha-tocopherol-deficient and -enriched diets for 14 d. Urine,
      serum, and feces were collected before and after dosing, and liver samples were
      collected after euthanization. Ultraperformance liquid chromatography
      electrospray ionization time-of-flight mass spectrometry and multivariate data
      analysis tools were used to analyze the samples. RESULTS: Three novel urinary
      metabolites of alpha-tocopherol were discovered in humans and mice: alpha
      carboxyethylhydroxychroman (alpha-CEHC) glycine, alpha-CEHC glycine glucuronide,
      and alpha-CEHC taurine. Another urinary metabolite, alpha-CEHC glutamine, was
      discovered in mice after alpha-CEHC gavage. Increases in liver fatty acids and
      decreases in serum and liver cholesterol were observed in mice fed the alpha
      tocopherol-enriched diet. CONCLUSION: Novel metabolites and metabolic pathways of
      vitamin E were identified by mass spectrometry-based metabolomics and will aid in
      understanding the disposition and roles of vitamin E in vivo.

PMID- 22952183
TI  - Long-term dietary heme iron and red meat intake in relation to endometrial cancer
      risk.
AB  - BACKGROUND: Heme and total iron, present in meat, have been hypothesized to
      promote carcinogenesis. Few prospective studies have examined the associations
      between intakes of heme and total iron, types of meat, and endometrial cancer
      risk. OBJECTIVE: We evaluated the associations between intakes of heme and total
      iron, types of meat, and risk of endometrial cancer in a large cohort of women.
      DESIGN: Among 60,895 women in the Swedish Mammography Cohort, 720 endometrial
      cancer cases were confirmed during 21 y of follow-up. RRs and 95% CIs were
      calculated by Cox proportional hazards models. RESULTS: A comparison of the
      highest with the lowest quartile showed a 20-30% higher risk of endometrial
      cancer for higher intakes of heme iron (RR: 1.24; 95% CI: 1.01, 1.53 for >=1.63
      compared with <0.69 mg/d), total iron (RR: 1.31; 95% CI: 1.07, 1.61 for >=15.09
      compared with <12.27 mg/d), and liver (RR: 1.29; 95% CI: 1.06, 1.56 for >=100
      compared with <100 g/wk). No statistically significant associations were observed
      between intakes of red and processed meats and endometrial cancer risk. RRs did
      not greatly differ when we stratified by BMI, parity, and intakes of alcohol,
      vitamin C, or zinc or when we excluded patients with diabetes. CONCLUSIONS: Our
      study suggests a modest positive association between heme iron, total iron, and
      liver intakes and endometrial cancer risk; no statistically significant
      associations were observed for intakes of other red and processed meats and
      endometrial cancer risk.

PMID- 22952182
TI  - No improvement in suboptimal vitamin A status with a randomized, double-blind,
      placebo-controlled trial of vitamin A supplementation in children with sickle
      cell disease.
AB  - BACKGROUND: Suboptimal vitamin A status is prevalent in children with type SS
      sickle cell disease (SCD-SS) and is associated with hospitalizations and poor
      growth and hematologic status. The supplemental vitamin A dose that optimizes
      suboptimal vitamin A status in this population is unknown. OBJECTIVE: The
      efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of
      vitamin A (300, 400, or 600 MUg retinyl palmitate/d) or vitamin A + zinc (10 or
      20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was
      assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum
      retinol concentration (<30 MUg/dL). DESIGN: In this randomized, double-blind,
      placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol
      binding protein, and relative-dose-response test) and disease-related illness
      events were assessed. RESULTS: Twelve months of vitamin A supplementation at the
      doses recommended for healthy US children (based on age and sex) failed to
      improve serum retinol values in either group (vitamin A: n = 23; vitamin A +
      zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (+/-SD) in
      serum retinol (3.6 +/- 2.8 MUg/dL) in those taking 600 MUg vitamin A/d was
      significantly different from the decrease (+/-SD; -2.8 +/- 2.4 MUg/dL) in those
      taking 300 MUg/d, which possibly suggests a dose-response relation (P < 0.05)
      with RDA doses. CONCLUSIONS: Compared with placebo, 12 mo of vitamin A
      supplementation at the RDA for healthy children did not improve serum retinol
      values in children with SCD-SS, which possibly suggests that higher doses are
      needed. However, the existence of alternative conclusions emphasizes the need for
      future research.

PMID- 22952184
TI  - Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response
      of glutathione peroxidase activity to selenium supplementation: a randomized
      controlled trial.
AB  - BACKGROUND: A genetic variant at codon 200 (Pro200Leu) of the gene encoding for
      glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with
      lower enzyme activity; however, the evidence is limited to in vitro and
      observational studies. OBJECTIVE: The objective was to determine whether the GPx1
      Pro200Leu genetic variants modify the response of whole-blood glutathione
      peroxidase (GPx) activity to selenium supplementation in patients with coronary
      artery disease in New Zealand. DESIGN: The results from 2 parallel-design, double
      blind trials were combined. Participants were randomly assigned to receive a
      daily supplement of 100 MUg Se as l-selenomethionine (n = 129) or placebo (n =
      126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at
      baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu
      polymorphism. RESULTS: Selenium supplementation increased whole-blood GPx
      activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude
      of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype
      interaction). In an exploratory analysis, a significant nutrient-gene interaction
      was apparent when baseline plasma selenium concentrations were included in the
      regression model (P = 0.006 for treatment-by-genotype * baseline selenium
      concentration interaction). Increases in GPx activity were 2-fold higher in Pro
      homozygotes than in participants carrying a Leu allele when baseline selenium
      concentrations were <=1.15 MUmol/L (P < 0.05). CONCLUSIONS: These results
      indicate that GPx1 Pro200Leu variants do not substantially modify the response of
      whole-blood GPx to selenium supplementation in individuals with relatively high
      plasma selenium concentrations. A nutrient-gene interaction was observed when the
      baseline selenium concentration was low, but this requires independent
      confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639
      and ACTRN12606000197538.

PMID- 22952185
TI  - Plasma and dietary omega-3 fatty acids, fish intake, and heart failure risk in
      the Physicians' Health Study.
AB  - BACKGROUND: Data on the relation of plasma and dietary omega-3 (n-3) fatty acids
      (FAs) with heart failure (HF) risk have been inconsistent. OBJECTIVE: We
      evaluated the relation of n-3 FAs with HF in US male physicians. DESIGN: We used
      nested case-control (n = 1572) and prospective cohort study designs (n = 19,097).
      Plasma phospholipid n-3 FAs were measured by using gas chromatography, and food
      frequency questionnaires were used to assess dietary n-3 FAs and fish intake.
      Incident HF was ascertained via annual follow-up questionnaires and validated in
      a subsample. RESULTS: The mean age was 58.7 y at blood collection. In a
      multivariable model, plasma alpha-linolenic acid (ALA) was associated with a
      lower risk of HF in a nonlinear fashion (P-quadratic trend = 0.02), and the
      lowest OR was observed in quintile 4 (0.66; 95% CI: 0.47, 0.94). Plasma EPA and
      DHA were not associated with HF, whereas plasma docosapentaenoic acid (DPA)
      showed a nonlinear inverse relation with HF for quintile 2 (OR: 0.55; 95% CI:
      0.39, 0.79). Dietary marine n-3 FAs showed a trend toward a lower risk of HF in
      quintile 4 (HR: 0.81; 95% CI: 0.64, 1.02) and a nonlinear pattern across
      quintiles. Fish intake was associated with a lower risk of HF, with RRs of ~0.70
      for all categories of fish consumption greater than one serving per month.
      CONCLUSIONS: Our data are consistent with an inverse and nonlinear relation of
      plasma phospholipid ALA and DPA, but not EPA or DHA, with HF risk. Fish
      consumption greater than once per month was associated with a lower HF risk.

PMID- 22952187
TI  - Systematic review and meta-analysis of school-based interventions to improve
      daily fruit and vegetable intake in children aged 5 to 12 y.
AB  - BACKGROUND: To our knowledge, no reviews have assessed the impact of a range of
      multi- and single-component school-based programs on daily fruit and vegetable
      intake by using a meta-analysis. OBJECTIVE: The aim of this study was to quantify
      the impact of school-based interventions on fruit and vegetable intake in
      children aged 5-12 y. DESIGN: A systematic literature review was carried out to
      identify randomized and nonrandomized controlled trials that were based in
      primary schools and designed to increase portions of daily fruit and vegetable
      intake. MEDLINE, Cochrane libraries, EMBASE, PsycINFO, and Educational
      Information Centre were searched from 1985 to 2009. Data were extracted, and mean
      effect sizes were calculated by using random effects models. RESULTS: A total of
      27 school-based programs involving 26,361 children were identified that met the
      inclusion criteria and assessed the daily weight of fruit and vegetable intake
      combined, fruit intake only, or vegetable intake only, and 21 studies were used
      in meta-analyses. The results of the meta-analyses indicated an improvement of
      0.25 portions (95% CI: 0.06, 0.43 portions) of fruit and vegetable daily intake
      if fruit juice was excluded and an improvement of 0.32 portions (95% CI: 0.14,
      0.50 portions) if fruit juice was included. Improvement was mainly due to
      increases in fruit consumption but not in vegetable consumption. The results of
      the meta-analyses for fruit (excluding juice) and vegetables separately indicated
      an improvement of 0.24 portions (95% CI: 0.05, 0.43 portions) and 0.07 portions
      (95% CI: -0.03, 0.16 portions), respectively. CONCLUSIONS: School-based
      interventions moderately improve fruit intake but have minimal impact on
      vegetable intake. Additional studies are needed to address the barriers for
      success in changing dietary behavior, particularly in relation to vegetables.

PMID- 22952188
TI  - Confined polymerization in porous organic frameworks with an ultrahigh surface
      area.

PMID- 22952186
TI  - Plasma carotenoids and vitamin C concentrations and risk of urothelial cell
      carcinoma in the European Prospective Investigation into Cancer and Nutrition.
AB  - BACKGROUND: Published associations between dietary carotenoids and vitamin C and
      bladder cancer risk are inconsistent. Biomarkers may provide more accurate
      measures of nutrient status. OBJECTIVE: We investigated the association between
      plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a
      case-control study nested within the European Prospective Investigation into
      Cancer and Nutrition. DESIGN: A total of 856 patients with newly diagnosed UCC
      were matched with 856 cohort members by sex, age at baseline, study center, date
      and time of blood collection, and fasting status. Plasma carotenoids (alpha- and
      beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin) were
      measured by using reverse-phase HPLC, and plasma vitamin C was measured by using
      a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using
      conditional logistic regression with adjustment for smoking status, duration, and
      intensity. RESULTS: UCC risk decreased with higher concentrations of the sum of
      plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64;
      95% CI: 0.44, 0.93; P-trend = 0.04). Plasma beta-carotene was inversely
      associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02).
      Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56;
      95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma
      vitamin C and risk of UCC. CONCLUSIONS: Although residual confounding by smoking
      or other factors cannot be excluded, higher concentrations of plasma carotenoids
      may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce
      risk of nonaggressive UCC.

PMID- 22952189
TI  - In situ generated iron oxide nanocrystals as efficient and selective catalysts
      for the reduction of nitroarenes using a continuous flow method.

PMID- 22952191
TI  - Metal-mediated synthesis of 1,4-di-tert-butyl-1,4-azaborine.

PMID- 22952192
TI  - Physical activity and psychological distress amongst Vietnamese living in the
      Mekong Delta.
AB  - OBJECTIVE: Regular physical activity may be an important contributor to
      psychological well-being. This link has not been explored in ethnically distinct,
      low- and middle-income countries (LMIC), especially in countries affected by war.
      This study aimed to examine the relationship between physical activity and levels
      of psychological distress in an epidemiological cross-representative sample of
      Vietnamese living in the Mekong Delta region of Vietnam. METHODS: The sample was
      drawn from an urban (Cn Th City) and a rural (H u Giang) region, using a multi
      stage probabilistic cluster sampling frame. The measures applied included the
      Composite International Diagnostic Interview (CIDI 2.0) yielding 12-month
      prevalence rates of common mental disorders, including anxiety, mood and
      substance use disorders; the Phan Vietnamese Psychiatric Scale (PVPS), a
      culturally specific self-report measure; and the Harvard Trauma Questionnaire.
      The Global Physical Activity Questionnaire (GPAQ version 1) was used to measure
      activity. Analyses were conducted using SAS software v.9.1.3. The population was
      assigned to three (high, moderate and low) physical activity levels. Analyses
      included chi-square tests and univariable and multivariable logistic models.
      RESULTS: Physical activity was greater in males, the middle-aged group (30-54
      years), those who were married, the rural population, less educated individuals
      and those who were employed. High physical activity was significantly associated
      with low levels of psychological distress (indexed by a combination of CIDI and
      PVPS cases identified) when controlling for socio-demographic factors and number
      of medical conditions). Membership of the lowest of the three physical activity
      groups was associated with a psychological distress odds ratio of 2.19 (95% CI
      1.28-3.75). The results remained consistent when analyses were undertaken
      separately for males and females. CONCLUSIONS: Low levels of physical activity
      appear to be associated with greater psychological distress in the Mekong Delta
      of Vietnam. The association remained after adjusting for the influence of socio
      demographic characteristics, exposure to past trauma, urban-rural residency and
      the presence of self-reported physical disorders. These data provide a foundation
      for exploring the role of physical activity as an adjunct to conventional
      interventions for common mental disorders in resource-poor LMIC countries.

PMID- 22952193
TI  - Osmotic demyelination syndrome: An under-recognised cause of delirium?

PMID- 22952194
TI  - Grape consumption's effects on fitness, muscle injury, mood, and perceived
      health.
AB  - Compounds found in the skins of grapes, including catechins, quercetin, and
      resveratrol, have been added to the diet of rodents and improved run time to
      exhaustion, fitness, and skeletal-muscle mitochondrial function. It is unknown if
      such effects occur in humans. The purpose of this experiment was to investigate
      whether 6 wk of daily grape consumption influenced maximal oxygen uptake
      (VO(2max)), work capacity, mood, perceived health status, inflammation, pain, and
      arm-function responses to a mild eccentric-exercise-induced arm-muscle injury.
      Forty recreationally active young adults were randomly assigned to consume a
      grape or placebo drink for 45 consecutive days. Before and after 42 d of
      supplementation, assessments were made of treadmill-running VO(2max), work
      capacity (treadmill performance time), mood (Profile of Mood States), and
      perceived health status (SF-36 Health Survey). The day after posttreatment
      treadmill tests were completed, 18 high-intensity eccentric actions of the
      nondominant elbow flexors were performed. Arm-muscle inflammation, pain, and
      function (isometric strength and range of motion) were measured before and on 2
      consecutive days after the eccentric exercise. Mixed-model ANOVA showed no
      significant effect of grape consumption on any of the outcomes. Six weeks of
      supplemental grape consumption by recreationally active young adults has no
      effect on VO(2max), work capacity, mood, perceived health status, inflammation,
      pain, or physical-function responses to a mild injury induced by eccentric
      exercise.

PMID- 22952195
TI  - A novel ligand delivery system to non-invasively visualize and therapeutically
      exploit the IL13Ralpha2 tumor-restricted biomarker.
AB  - Our objective was to exploit a novel ligand-based delivery system for targeting
      diagnostic and therapeutic agents to cancers that express interleukin 13 receptor
      alpha 2 (IL13Ralpha2), a tumor-restricted plasma membrane receptor overexpressed
      in glioblastoma multiforme (GBM), meningiomas, peripheral nerve sheath tumors,
      and other peripheral tumors. On the basis of our prior work, we designed a novel
      IL13Ralpha2-targeted quadruple mutant of IL13 (TQM13) to selectively bind the
      tumor-restricted IL13Ralpha2 with high affinity but not significantly interact
      with the physiologically abundant IL13Ralpha1/IL4Ralpha heterodimer that is also
      expressed in normal brain. We then assessed the in vitro binding profile of TQM13
      and its potential to deliver diagnostic and therapeutic radioactivity in vivo.
      Surface plasmon resonance (SPR; Biacore) binding experiments demonstrated that
      TQM13 bound strongly to recombinant IL13Ralpha2 (Kd~5 nM). In addition,
      radiolabeled TQM13 specifically bound IL13Ralpha2-expressing GBM cells and
      specimens but not normal brain. Of importance, TQM13 did not functionally
      activate IL13Ralpha1/IL4Ralpha in cells or bind to it in SPR binding assays, in
      contrast to wtIL13. Furthermore, in vivo targeting of systemically delivered
      radiolabeled TQM13 to IL13Ralpha2-expressing subcutaneous tumors was demonstrated
      and confirmed non-invasively for the first time with 124I-TQM13 positron emission
      tomography imaging. In addition, 131I-TQM13 demonstrated in vivo efficacy against
      subcutaneous IL13Ralpha2-expressing GBM tumors and in an orthotopic synergeic
      IL13Ralpha2-positive murine glioma model, as evidenced by statistically
      significant survival advantage. Our results demonstrate that we have successfully
      generated an optimized biomarker-targeted scaffolding that exhibited specific
      binding activity toward the tumor-associated IL13Ralpha2 in vitro and potential
      to deliver diagnostic and therapeutic payloads in vivo.

PMID- 22952196
TI  - Outcomes of the oldest patients with primary CNS lymphoma treated at Memorial
      Sloan-Kettering Cancer Center.
AB  - Up to 20% of all primary CNS lymphoma (PCNLS) patients are aged 80 years or
      older, yet data are limited on how best to treat this rapidly growing population.
      Despite demographic pressures and the proven efficacy of methotrexate (MTX)-based
      regimens, automatic de-escalation of care based on age is standard practice
      outside of tertiary care centers. We performed a retrospective review of all
      PCNSL patients aged 80 years or older treated at Memorial Sloan-Kettering Cancer
      Center from 1993 to 2011. Demographic and clinical variables were evaluated as
      predictors of survival by multivariate analysis. Twenty-three of 24 patients were
      treated with chemotherapy (92% with high-dose MTX, typically in combination with
      vincristine and procarbazine). One patient received ocular radiation alone for
      disease limited to the eyes. Response to treatment was noted in 62.5% of
      patients; 9 (37.5%) had refractory disease. Median overall survival was 7.9
      months (95% confidence interval [CI]: 5.8-53), and median progression-free
      survival was 6.5 months (95% CI: 4.4-29.5). Two-year survival rate was 33%; 3
      year survival rate was 17%. Three patients lived more than 4 years postdiagnosis.
      Most patients tolerated therapy well, and despite low baseline creatinine
      clearance, no significant renal toxicity was noted. Response status and deep
      brain involvement were identified as the most important predictors of survival.
      Multidrug regimens containing high-dose MTX are feasible and efficacious among
      the oldest patients, particularly those who achieve a complete response by their
      fifth treatment cycle. Aggressive therapy should be offered to select patients
      irrespective of advanced age.

PMID- 22952197
TI  - Ionizing radiation and the risk of brain and central nervous system tumors: a
      systematic review.
AB  - Although exposure to moderate-to-high doses of ionizing radiation is the only
      established environmental risk factor for brain and CNS tumors, it is not clear
      whether this relationship differs across tumor subtypes, by sex or age at
      exposure, or at the low-to-moderate range of exposure. This systematic review
      summarizes the epidemiologic evidence on the association between ionizing
      radiation exposure and risk of brain/CNS tumors. Articles included in this review
      estimated radiation exposure doses to the brain and reported excess relative risk
      (ERR) estimates for brain/CNS tumors. Eight cohorts were eligible for inclusion
      in the analysis. Average age at exposure ranged from 8 months to 26 years. Mean
      dose to the brain ranged from 0.07 to 10 Gy. Elevated risks for brain/CNS tumors
      were consistently observed in relation to ionizing radiation exposure, but the
      strength of this association varied across cohorts. Generally, ionizing radiation
      was more strongly associated with risk for meningioma compared with glioma. The
      positive association between ionizing radiation exposure and risk for glioma was
      stronger for younger vs older ages at exposure. We did not observe an effect
      modification on the risk for meningioma by sex, age at exposure, time since
      exposure, or attained age. The etiologic role of ionizing radiation in the
      development of brain/CNS tumors needs to be clarified further through additional
      studies that quantify the association between ionizing radiation and risk for
      brain/CNS tumors at low-to-moderate doses, examine risks across tumor subtypes,
      and account for potential effect modifiers.

PMID- 22952198
TI  - Clinical and neuroanatomical predictors of cerebellar mutism syndrome.
AB  - Cerebellar mutism syndrome (CMS) is an important medical challenge in the
      management of pediatric posterior fossa brain tumors, because it occurs in a
      subset of children following tumor resection. A definitive clinical profile and
      neuroanatomical substrate associated with CMS remains unclear. We investigated
      the relationship between presurgical and clinical variables and the incidence of
      CMS, along with diffusion tensor imaging, to characterize the integrity of
      cerebello-thalamo-cerebral white matter pathways. Seventeen children with
      posterior fossa tumors and CMS, 34 children with posterior fossa tumors without
      CMS, and 28 healthy children were enrolled in this study. Bilateral cerebello
      thalamo-cerebral pathways were delineated and segmented into anatomical regions.
      Mean integrity measures for each region were compared among children with CMS,
      children without CMS, and healthy children. Left-handedness, medulloblastoma
      histology, and larger tumor size distinguished between patients with CMS and
      patients without CMS (P < .04). Right cerebellar white matter within the
      cerebello-thalamo-cerebral pathway was compromised in children with CMS relative
      to children without CMS and healthy children (P < .02). We provide a potential
      schema for CMS risk among children treated for posterior fossa tumors. Left
      handed children treated for medulloblastoma may be the most at risk for CMS, and
      unilateral, localized damage within the cerebello-thalamo-cerebral pathway at the
      level of the right cerebellum is implicated in the presentation of CMS. This
      disruption in communication between the right cerebellum and left frontal cortex
      may contribute to speech-language problems observed in children with CMS. Our
      findings may be relevant for surgical planning and speech-language therapy to
      mitigate symptoms of CMS.

PMID- 22952199
TI  - Highly enantio- and diastereoselective reactions of gamma-substituted butenolides
      through direct vinylogous conjugate additions.

PMID- 22952200
TI  - Effects of Ramadan on the diurnal variations of repeated-sprint performances.
AB  - PURPOSE: This study examined the effects of Ramadan on cycling repeated-sprint
      ability (RSA) and corresponding diurnal variations. METHODS: Twelve active men
      performed an RSA test (5 * 6-s maximal sprints interspersed with 24 s passive
      recovery) during morning and afternoon sessions 1 wk before Ramadan (BR), during
      the second (R2) and the fourth (R4) weeks of Ramadan, and 2 wk after Ramadan
      (AR). Maximal voluntary contraction was assessed before (MVCpre), immediately
      after (MVCpost), and 5 min after the RSA test (MVCpost5). Moreover, hematocrit,
      hemoglobin, and plasma sodium and potassium (K+) concentrations were measured at
      rest and after the RSA test and MVCpost. RESULTS: Overall, peak power (Ppeak)
      during the RSA test decreased throughout the 5 sprints. Ppeak measured in the
      first sprint and MVCpre were lower during Ramadan than BR in the afternoon (P <
      .05) and higher in the afternoon than the morning BR and AR (P < .05). However,
      this diurnal rhythmicity was not found for the last 4 sprints' Ppeak, MVCpost,
      and MVCpost5 in all testing periods. Furthermore, the last 4 sprints' Ppeak,
      MVCpost, MVCpost5, and morning MVCpre were not affected by Ramadan. [K+] measured
      at rest and after the RSA test and MVCpost were higher during Ramadan than BR in
      the afternoon (P < .05) and higher in the afternoon than the morning during
      Ramadan (P < .05). CONCLUSIONS: Fatigability is higher in the afternoon during
      Ramadan, and, therefore, training and competition should be scheduled at the time
      of day when physical performance is less affected.

PMID- 22952201
TI  - Minimally supervised multimodal exercise to reduce falls risk in economically and
      educationally disadvantaged older adults.
AB  - Few studies have evaluated the benefit of providing exercise to underprivileged
      older adults at risk for falls. Economically and educationally disadvantaged
      older adults with previous falls (mean age 79.06, SD = 4.55) were randomized to 4
      mo of multimodal exercise provided as fully supervised center-based (FS, n = 45),
      minimally supervised home-based (MS, n = 42), or to nonexercise controls (C, n =
      32). Comparing groups on the mean change in fall-relevant mobility task
      performance between baseline and 4 mo and compared with the change in C, both FS
      and MS had significantly greater reduction in timed up-and-go, F(2,73) = 5.82, p
      = .004, eta2 p = .14, and increase in tandem-walk speed, F(2,73) = 7.71, p < .001
      eta2 p = .17. Change in performance did not statistically differ between FS and
      MS. In community-dwelling economically and educationally disadvantaged older
      adults with a history of falls, minimally supervised home-based and fully
      supervised center-based exercise programs may be equally effective in improving
      fall-relevant functional mobility. 

PMID- 22952202
TI  - Obesity, diabetes mellitus, and cancer.

PMID- 22952208
TI  - Effects of tricuspid valve regurgitation on clinical and echocardiographic
      outcome in patients with cardiac resynchronization therapy.
AB  - AIMS: The severity of tricuspid regurgitation (TR) is a predictor of outcome
      among heart failure patients. The interaction between cardiac resynchronization
      therapy (CRT) and TR has not been described. In this study, we examined the
      effect of pre-implant TR, and worsened TR post-implant, on response to CRT and
      overall survival. METHODS AND RESULTS: We included all patients with successfully
      implanted CRT systems between 2007 and 2010. Patients were divided into two
      groups pre-implant: (Gp 1) no-or-mild TR; and (Gp 2) moderate-or-severe TR. Post
      implant, patients were divided into two groups: (Gp A) improved or stable TR; and
      (Gp B) worsened TR. The clinical and echocardiographic outcome of all patients
      was assessed. The study included 193 patients. Thirty-five subjects (18%) had
      moderate or severe TR pre-implant (Gp 2). Baseline echo parameters and 6 min walk
      distance were worse in Gp 2 compared with Gp 1 (mild or no TR). There was no
      significant difference in clinical response to CRT between the two groups.
      However, Gp 2 had a significantly lower echocardiographic response (35 vs. 60%, P
      = 0.01) and higher mortality over 3 years (OR = 6.70, 95% CI = 1.8-24.5, P =
      0.004). Post-implant, 25 patients (13%) developed worsened TR (Gp B), not
      associated with deterioration in right ventricle function or elevation in
      pulmonary artery pressure. Worsened TR predicted a reduced clinical response to
      CRT (42 vs. 70%, P = 0.006), when compared with Gp A. CONCLUSIONS: The presence
      of baseline moderate or severe TR is associated with increased mortality but does
      not predict clinical or echocardiographic response to CRT. Patients with worsened
      TR following CRT are less likely to clinically respond to CRT. Pacing leads
      passing through the tricuspid valve may worsen TR. It is conceivable that
      avoidance of lead-induced TR by alternative implantation techniques could improve
      the response rate to CRT.

PMID- 22952203
TI  - Upper extremity muscle volumes and functional strength after resistance training
      in older adults.
AB  - Aging leads to a decline in strength and an associated loss of independence. The
      authors examined changes in muscle volume, maximum isometric joint moment,
      functional strength, and 1-repetition maximum (1RM) after resistance training
      (RT) in the upper extremity of older adults. They evaluated isometric joint
      moment and muscle volume as predictors of functional strength. Sixteen healthy
      older adults (average age 75 +/- 4.3 yr) were randomized to a 6-wk upper
      extremity RT program or control group. The RT group increased 1RM significantly
      (p < .01 for all exercises). Compared with controls, randomization to RT led to
      greater functional pulling strength (p = .003), isometric shoulder-adduction
      moment (p = .041), elbow-flexor volume (p = .017), and shoulder-adductor volume
      (p = .009). Shoulder-muscle volumes and isometric moments were good predictors of
      functional strength. The authors conclude that shoulder strength is an important
      factor for performing functional reaching and pulling tasks and a key target for
      upper extremity RT interventions.

PMID- 22952209
TI  - A randomized controlled trial of hospital-based case management in cancer care: a
      general practitioner perspective.
AB  - BACKGROUND: Case management (CM) models based on experienced nurses are
      increasingly used to improve coordination and continuity of care for patients
      with complex health care needs. Anyway, little is known about the effects of
      hospital-based CM in cancer care.  Aim. To analyse the effects of hospital-based
      CM on (i) GPs' evaluation of information from the hospital and collaboration with
      the hospital staff and (ii) patients' contacts with GPs during daytime and out of
      hours. DESIGN: A randomized controlled trial allocated 280 colorectal cancer
      patients 1:1 to either a control group or CM intervention. SETTING: Patients were
      recruited at a Danish surgical department. METHODS: An ad hoc piloted
      questionnaire was sent to all patients' GPs 30 weeks after patients' recruitment
      and the responses from the two groups of GPs were compared. Registry data on
      patients' contacts with general practice during daytime and out of hours were
      collected 9 months after recruitment and the data from the two groups were
      compared quarterly. RESULTS: CM was associated with an overall tendency towards
      more positive GP evaluations, which for 3 of 20 items reached statistical
      significance. Statistically significantly fewer GPs of CM patients reported
      contacting the hospital. CM did not affect the number of patient contacts with
      the GPs during the daytime, but CM patients showed a tendency towards more
      contacts to the out-of-hours GP services than non-CM patients. CONCLUSIONS: CM
      was appreciated by the GPs and reduced their need for subsequent hospital
      contact. CM increased the number of patient contacts to the out-of-hours GP
      services.

PMID- 22952210
TI  - The great escape: microbiotal LPS takes a toll on the liver.
AB  - The interaction between the intestinal microbiota and host is much more complex
      than previously appreciated, and we are now learning that it can have an impact
      on extraintestinal human diseases. In this issue of the journal (beginning on
      page 1090), Lin and colleagues present important data linking the microbiota,
      lipopolysaccharide (LPS), and toll-like receptor (TLR)4 with hepatitis in a mouse
      model. These provocative results and those from other recent studies highlight
      the microbiota as a potential target for therapeutic intervention in several
      liver diseases.

PMID- 22952212
TI  - Systemic treatment of advanced pancreatic cancer--step by step progress.

PMID- 22952213
TI  - Darexaban for the prevention of venous thromboembolism in Asian patients
      undergoing orthopedic surgery: results from 2 randomized, placebo-controlled,
      double-blind studies.
AB  - OBJECTIVE: To evaluate the efficacy and safety of darexaban (YM150) in Asian
      patients undergoing total hip or total knee arthroplasty. METHODS: In 2 phase
      II/III multicenter, randomized, double-blind, placebo-controlled, parallel-group
      studies, patients were randomized to oral darexaban 15 mg twice daily (bid),
      darexaban 30 mg bid, oral placebo bid, or subcutaneous enoxaparin 20 mg bid.
      Primary efficacy outcome for both studies was total venous thromboembolism (VTE)
      incidence. RESULTS: Both darexaban doses were statistically significantly
      superior to placebo for total VTE incidence (hip study: darexaban 15 mg bid
      [2.9%] vs placebo [17.1%], P < .001; darexaban 30 mg bid [5.2%] vs placebo
      [17.1%], P = .003; and knee study: darexaban 15 mg bid [27.2%] vs placebo
      [52.8%], P = .002; darexaban 30 mg bid [15.5%] vs placebo [52.8%], P < .001). In
      both studies, the incidence of bleeding events was low across all treatment
      groups. CONCLUSION: Darexaban is effective and well tolerated as VTE prophylaxis
      in Asian patients undergoing elective major orthopedic surgery.

PMID- 22952214
TI  - Peripheral nerve blockade and neonatal limb ischemia: our experience and
      literature review.
AB  - Considering the high frequency of bleeding complications following fibrinolytic
      treatment in neonates, peripheral nerve blockade (PNB) has been proposed alone or
      in association with lower doses of tissue plasminogen activator, as a possible
      new therapeutic approach in the management of neonatal limb ischemia (LI)
      secondary to vasospasm and/or thrombosis. The present article provides a review
      of the current knowledge about the topic, in order to evaluate the efficacy and
      safety of this therapeutic approach. According to the few case reports documented
      in literature and to our experience, PNB could be considered as valid procedure
      for the treatment of LI, especially during neonatal period, when the risk of
      serious bleeding associated with fibrinolytic or anticoagulant therapy is higher.
      Peripheral nerve blockade resulted in a safe and effective procedure for the
      treatment of neonatal vascular spasm and thrombosis. 

PMID- 22952215
TI  - Stroke prevention in atrial fibrillation: impact of novel oral anticoagulants.
AB  - New orally administered anticoagulants will simplify stroke-prevention strategies
      in patients with atrial fibrillation (AF). Novel anticoagulants, such as
      dabigatran etexilate, a direct thrombin inhibitor, and rivaroxaban, a direct
      factor Xa inhibitor, have been approved by the US Food and Drug Administration
      for the prevention of stroke and systemic embolism in patients with nonvalvular
      AF. In addition, the factor Xa inhibitor apixaban has been reported to be as
      effective as warfarin in a large, randomized clinical trial, and the efficacy of
      edoxaban is being assessed in a phase III warfarin comparison trial. This review
      discusses the limitations of vitamin K antagonist therapy for patients with AF
      and establishes the need for alternative, effective anticoagulation with an
      improved benefit-risk ratio for the prevention of stroke. Novel anticoagulants
      have the potential to provide convenient, effective stroke prophylaxis without
      many of the issues inherent in the use of traditional agents.

PMID- 22952216
TI  - Sorafenib has potent antitumor activity against multiple myeloma in vitro, ex
      vivo, and in vivo in the 5T33MM mouse model.
AB  - Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of
      clonal plasma blasts/plasma cells within the bone marrow that relies on multiple
      signaling cascades, including tyrosine kinase activated pathways, to proliferate
      and evade cell death. Despite emerging new treatment strategies, multiple myeloma
      remains at present incurable. Thus, novel approaches targeting several signaling
      cascades by using the multi-tyrosine kinase inhibitor (TKI), sorafenib, seem a
      promising treatment approach for multiple myeloma. Here, we show that sorafenib
      induces cell death in multiple myeloma cell lines and in CD138(+)-enriched
      primary multiple myeloma patient samples in a caspase-dependent and -independent
      manner. Furthermore, sorafenib has a strong antitumoral and -angiogenic activity
      in the 5T33MM mouse model leading to increased overall survival. Multiple myeloma
      cells undergo autophagy in response to sorafenib, and inhibition of this
      cytoprotective pathway potentiated the efficacy of this TKI. Mcl-1, a survival
      factor in multiple myeloma, is downregulated at the protein level by sorafenib
      allowing for the execution of cell death, as ectopic overexpression of this
      protein protects multiple myeloma cells. Concomitant targeting of Mcl-1 by
      sorafenib and of Bcl-2/Bcl-xL by the antagonist ABT737 improves the efficacy of
      sorafenib in multiple myeloma cell lines and CD138(+)-enriched primary cells in
      the presence of bone marrow stromal cells. Altogether, our data support the use
      of sorafenib as a novel therapeutic modality against human multiple myeloma, and
      its efficacy may be potentiated in combination with ABT737.

PMID- 22952217
TI  - A synthetic matrix with independently tunable biochemistry and mechanical
      properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma
      model.
AB  - Better understanding of the biophysical and biochemical cues of the tumor
      extracellular matrix environment that influence metastasis may have important
      implications for new cancer therapeutics. Initial exploration into this question
      has used naturally derived protein matrices that suffer from variability, poor
      control over matrix biochemistry, and inability to modify the matrix biochemistry
      and mechanics. Here, we report the use of a synthetic polymer-based scaffold
      composed primarily of poly(ethylene glycol), or PEG, modified with bioactive
      peptides to study murine models of lung adenocarcinoma. In this study, we focus
      on matrix-derived influences on epithelial morphogenesis of a metastatic cell
      line (344SQ) that harbors mutations in Kras and p53 (trp53) and is prone to a
      microRNA-200 (miR-200)-dependent epithelial-mesenchymal transition (EMT) and
      metastasis. The modified PEG hydrogels feature biospecific cell adhesion and cell
      mediated proteolytic degradation with independently adjustable matrix stiffness.
      344SQ encapsulated in bioactive peptide-modified, matrix metalloproteinase
      degradable PEG hydrogels formed lumenized epithelial spheres comparable to that
      seen with three-dimensional culture in Matrigel. Altering both matrix stiffness
      and the concentration of cell-adhesive ligand significantly influenced epithelial
      morphogenesis as manifest by differences in the extent of lumenization, in
      patterns of intrasphere apoptosis and proliferation, and in expression of
      epithelial polarity markers. Regardless of matrix composition, exposure to TGF
      beta induced a loss of epithelial morphologic features, shift in expression of
      EMT marker genes, and decrease in mir-200 levels consistent with EMT. Our
      findings help illuminate matrix-derived cues that influence epithelial
      morphogenesis and highlight the potential utility that this synthetic matrix
      mimetic tool has for cancer biology.

PMID- 22952219
TI  - RECIST: no longer the sharpest tool in the oncology clinical trials toolbox--
      point.
AB  - Although "response" has been an attractive term for oncologists and patients,
      oncologists really want to know which therapy to start for a given patient and
      when to discontinue that therapy in favor of an alternative. In efficacy trials,
      cancer therapeutics have conventionally been assessed by endpoints that are based
      on the categorical Response Evaluation Criteria In Solid Tumors (RECIST) system.
      In this article, we make the case for a new paradigm in which therapeutics are
      assessed on a continuous scale by evidence of efficacy, using a variety of
      quantitative tools that take advantage of technologic innovations and increasing
      understanding of cancer biology. The new paradigm relies on randomized
      comparisons between investigational arms and control arms, as historical controls
      are unavailable or unreliable for these quantitative measures. We discuss
      multiple limitations of RECIST, including its overemphasis on tumor regression,
      concerns about the accuracy of tumor measurements and the validity of comparisons
      with historical controls, and its inadequacy in disease settings in which tumor
      measurements on cross-sectional imaging are difficult or uninformative. We
      discuss how the new paradigm overcomes these limitations and provides a framework
      for answering the key questions of the oncologist and improving patient outcomes.

PMID- 22952218
TI  - Overcoming limitations in nanoparticle drug delivery: triggered, intravascular
      release to improve drug penetration into tumors.
AB  - Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease
      normal tissue toxicity by improving drug specificity to tumors. The enhanced
      permeability and retention effect can permit passive accumulation into tumor
      interstitium. However, suboptimal delivery is achieved with most nanoparticles
      because of heterogeneities of vascular permeability, which limits nanoparticle
      penetration. Furthermore, slow drug release limits bioavailability. We developed
      a fast drug-releasing liposome triggered by local heat that has already shown
      substantial antitumor efficacy and is in human trials. Here, we show that
      thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor
      vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors
      in window chambers and histologic analysis of flank tumors illustrates that
      intravascular drug release increases free drug in the interstitial space. This
      increases both the time that tumor cells are exposed to maximum drug levels and
      the drug penetration distance, compared with free drug or traditional pegylated
      liposomes. These improvements in drug bioavailability establish a new paradigm in
      drug delivery: rapidly triggered drug release in the tumor bloodstream.

PMID- 22952220
TI  - Why RECIST works and why it should stay--reply to counterpoint.

PMID- 22952221
TI  - Why RECIST works and why it should stay--counterpoint.
AB  - Assessing that the efficacy of a cancer therapeutic is an integral part of its
      path to regulatory approval, we review the history that led to our current
      assessment method, Response Evaluation Criteria in Solid Tumors (RECIST). We
      describe the efforts of Moertel and Hanley to standardize response assessments in
      lymphoid malignancies and how this was adapted in the World Health Organization
      (WHO) criteria. Two decades later, RECIST was advanced to streamline WHO and
      improve its reproducibility. We describe the ways in which thresholds established
      by Moertel and Hanley to provide accuracy and reproducibility evolved to become
      measures of efficacy and why they have been valuable. While we recognize RECIST
      is far from perfect-in need of modification as a measure of efficacy for some
      agents and in some diseases-for the majority of solid tumors, it is very
      valuable. We argue that over time, the efficacy thresholds established by WHO and
      then RECIST have proved their worth, and we summarize 10 years of U.S. Food and
      Drug Administration (FDA) approvals in solid tumors to support our position that
      current RECIST thresholds should be retained.

PMID- 22952222
TI  - RECIST: no longer the sharpest tool in the oncology clinical trials toolbox-
      reply to point.

PMID- 22952223
TI  - Hallmarks of processivity in glycoside hydrolases from crystallographic and
      computational studies of the Serratia marcescens chitinases.
AB  - Degradation of recalcitrant polysaccharides in nature is typically accomplished
      by mixtures of processive and nonprocessive glycoside hydrolases (GHs), which
      exhibit synergistic activity wherein nonprocessive enzymes provide new sites for
      productive attachment of processive enzymes. GH processivity is typically
      attributed to active site geometry, but previous work has demonstrated that
      processivity can be tuned by point mutations or removal of single loops. To gain
      additional insights into the differences between processive and nonprocessive
      enzymes that give rise to their synergistic activities, this study reports the
      crystal structure of the catalytic domain of the GH family 18 nonprocessive
      endochitinase, ChiC, from Serratia marcescens. This completes the structural
      characterization of the co-evolved chitinolytic enzymes from this bacterium and
      enables structural analysis of their complementary functions. The ChiC catalytic
      module reveals a shallow substrate-binding cleft that lacks aromatic residues
      vital for processivity, a calcium-binding site not previously seen in GH18
      chitinases, and, importantly, a displaced catalytic acid (Glu-141), suggesting
      flexibility in the catalytic center. Molecular dynamics simulations of two
      processive chitinases (ChiA and ChiB), the ChiC catalytic module, and an
      endochitinase from Lactococcus lactis show that the nonprocessive enzymes have
      more flexible catalytic machineries and that their bound ligands are more
      solvated and flexible. These three features, which relate to the more dynamic on
      off ligand binding processes associated with nonprocessive action, correlate to
      experimentally measured differences in processivity of the S. marcescens
      chitinases. These newly defined hallmarks thus appear to be key dynamic metrics
      in determining processivity in GH enzymes complementing structural insights.

PMID- 22952224
TI  - Identification and quantification of a new family of peptide endocannabinoids
      (Pepcans) showing negative allosteric modulation at CB1 receptors.
AB  - The alpha-hemoglobin-derived dodecapeptide RVD-hemopressin (RVDPVNFKLLSH) has
      been proposed to be an endogenous agonist for the cannabinoid receptor type 1
      (CB(1)). To study this peptide, we have raised mAbs against its C-terminal part.
      Using an immunoaffinity mass spectrometry approach, a whole family of N
      terminally extended peptides in addition to RVD-Hpalpha were identified in rodent
      brain extracts and human and mouse plasma. We designated these peptides Pepcan-12
      (RVDPVNFKLLSH) to Pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH), referring to peptide
      length. The most abundant Pepcans found in the brain were tested for CB(1)
      receptor binding. In the classical radioligand displacement assay, Pepcan-12 was
      the most efficacious ligand but only partially displaced both [(3)H]CP55,940 and
      [(3)H]WIN55,212-2. The data were fitted with the allosteric ternary complex
      model, revealing a cooperativity factor value alpha < 1, thus indicating a
      negative allosteric modulation. Dissociation kinetic studies of [(3)H]CP55,940 in
      the absence and presence of Pepcan-12 confirmed these results by showing
      increased dissociation rate constants induced by Pepcan-12. A fluorescently
      labeled Pepcan-12 analog was synthesized to investigate the binding to CB(1)
      receptors. Competition binding studies revealed K(i) values of several Pepcans in
      the nanomolar range. Accordingly, using competitive ELISA, we found low nanomolar
      concentrations of Pepcans in human plasma and ~100 pmol/g in mouse brain.
      Surprisingly, Pepcan-12 exhibited potent negative allosteric modulation of the
      orthosteric agonist-induced cAMP accumulation, [(35)S]GTPgammaS binding, and
      CB(1) receptor internalization. Pepcans are the first endogenous allosteric
      modulators identified for CB(1) receptors. Given their abundance in the brain,
      Pepcans could play an important physiological role in modulating endocannabinoid
      signaling.

PMID- 22952225
TI  - Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin
      hydroxylation and epoxidation reactions.
AB  - The majority of characterized cytochrome P450 enzymes in actinomycete secondary
      metabolic pathways are strictly substrate-, regio-, and stereo-specific. Examples
      of multifunctional biosynthetic cytochromes P450 with broader substrate and regio
      specificity are growing in number and are of particular interest for biosynthetic
      and chemoenzymatic applications. MycG is among the first P450 monooxygenases
      characterized that catalyzes both hydroxylation and epoxidation reactions in the
      final biosynthetic steps, leading to oxidative tailoring of the 16-membered ring
      macrolide antibiotic mycinamicin II in the actinomycete Micromonospora
      griseorubida. The ordering of steps to complete the biosynthetic process involves
      a complex substrate recognition pattern by the enzyme and interplay between three
      tailoring modifications as follows: glycosylation, methylation, and oxidation. To
      understand the catalytic properties of MycG, we structurally characterized the
      ligand-free enzyme and its complexes with three native metabolites. These include
      substrates mycinamicin IV and V and their biosynthetic precursor mycinamicin III,
      which carries the monomethoxy sugar javose instead of the dimethoxylated sugar
      mycinose. The two methoxy groups of mycinose serve as sensors that mediate
      initial recognition to discriminate between closely related substrates in the
      post-polyketide oxidative tailoring of mycinamicin metabolites. Because x-ray
      structures alone did not explain the mechanisms of macrolide hydroxylation and
      epoxidation, paramagnetic NMR relaxation measurements were conducted. Molecular
      modeling based on these data indicates that in solution substrate may penetrate
      the active site sufficiently to place the abstracted hydrogen atom of mycinamicin
      IV within 6 A of the heme iron and ~4 A of the oxygen of iron-ligated water.

PMID- 22952226
TI  - A genetic model of substrate reduction therapy for mucopolysaccharidosis.
AB  - Inherited defects in the ability to catabolize glycosaminoglycans result in
      lysosomal storage disorders known as mucopolysaccharidoses (MPS), causing severe
      pathology, particularly in the brain. Enzyme replacement therapy has been used to
      treat mucopolysaccharidoses; however, neuropathology has remained refractory to
      this approach. To test directly whether substrate reduction might be feasible for
      treating MPS disease, we developed a genetic model for substrate reduction
      therapy by crossing MPS IIIa mice with animals partially deficient in heparan
      sulfate biosynthesis due to heterozygosity in Ext1 and Ext2, genes that encode
      the copolymerase required for heparan sulfate chain assembly. Reduction of
      heparan sulfate by 30-50% using this genetic strategy ameliorated the amount of
      disease-specific biomarker and pathology in multiple tissues, including the
      brain. In addition, we were able to demonstrate that substrate reduction therapy
      can improve the efficacy of enzyme replacement therapy in cell culture and in
      mice. These results provide proof of principle that targeted inhibition of
      heparan sulfate biosynthetic enzymes together with enzyme replacement might prove
      beneficial for treating mucopolysaccharidoses.

PMID- 22952227
TI  - beta-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1)
      channel.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel
      activated by multiple stimuli and is implicated in a variety of pain disorders.
      Dynamic sensitization of TRPV1 activity by A-kinase anchoring protein 150
      demonstrates a critical role for scaffolding proteins in nociception, yet few
      studies have investigated scaffolding proteins capable of mediating receptor
      desensitization. In this study, we identify beta-arrestin-2 as a scaffolding
      protein that regulates TRPV1 receptor activity. We report beta-arrestin-2
      association with TRPV1 in multiple cell models. Moreover, siRNA-mediated
      knockdown of beta-arrestin-2 in primary cultures resulted in a significant
      increase in both initial and repeated responses to capsaicin.
      Electrophysiological analysis further revealed significant deficits in TRPV1
      desensitization in primary cultures from beta-arrestin-2 knock-out mice compared
      with wild type. In addition, we found that beta-arrestin-2 scaffolding of
      phosphodiesterase PDE4D5 to the plasma membrane was required for TRPV1
      desensitization. Importantly, inhibition of PDE4D5 activity reversed beta
      arrestin-2 desensitization of TRPV1. Together, these results identify a new
      endogenous scaffolding mechanism that regulates TRPV1 ligand binding and
      activation.

PMID- 22952228
TI  - Tight control of trehalose content is required for efficient heat-induced cell
      elongation in Candida albicans.
AB  - The ability to form hyphae in the human pathogenic fungus Candida albicans is a
      prerequisite for virulence. It contributes to tissue infection, biofilm
      formation, as well as escape from phagocytes. Cell elongation triggered by human
      body temperature involves the essential heat shock protein Hsp90, which
      negatively governs a filamentation program dependent upon the Ras-protein kinase
      A (PKA) pathway. Tight regulation of Hsp90 function is required to ensure fast
      appropriate response and maintenance of a wide range of regulatory and signaling
      proteins. Client protein activation by Hsp90 relies on a conformational change of
      the chaperone, whose ATPase activity is competitively inhibited by geldanamycin.
      We demonstrate a novel regulatory mechanism of heat- and Hsp90-dependent induced
      morphogenesis, whereby the nonreducing disaccharide trehalose acts as a negative
      regulator of Hsp90 release. By means of a mutant strain deleted for Gpr1, the G
      protein-coupled receptor upstream of PKA, we demonstrate that elevated trehalose
      content in that strain, resulting from misregulation of enzymatic activities
      involved in trehalose metabolism, disrupts the filamentation program in response
      to heat. Addition of geldanamycin does not result in hyphal extensions at 30 
      degrees C in the gpr1Delta/gpr1Delta mutant as it does in wild type cells. In
      addition, validamycin, a specific inhibitor of trehalase, the trehalose-degrading
      enzyme, inhibits cell elongation in response to heat and geldanamycin. These
      results place Gpr1 as a regulator of trehalose metabolism in C. albicans and
      illustrate that trehalose modulates Hsp90-dependent activation of client proteins
      and signaling pathways leading to filamentation in the human fungal pathogen.

PMID- 22952229
TI  - Bromodomain and extra-terminal (BET) bromodomain inhibition activate
      transcription via transient release of positive transcription elongation factor b
      (P-TEFb) from 7SK small nuclear ribonucleoprotein.
AB  - By phosphorylating elongation factors and the C-terminal domain of RNA polymerase
      II, the positive transcription elongation factor b (P-TEFb) is the critical
      kinase for transcription elongation and co-transcriptional processing of
      eukaryotic genes. It exists in inactive small nuclear ribonucleoprotein (7SK
      snRNP) and active (free P-TEFb) complexes in cells. The P-TEFb equilibrium
      determines the state of cellular activation, proliferation, and differentiation.
      Free P-TEFb, which is required for growth, can be recruited to RNA polymerase II
      via transcription factors, BRD4, or the super elongation complex (SEC). UV light,
      various signaling cascades, transcriptional blockade, or compounds such as
      hexamethylene bisacetamide (HMBA), suberoylanilide hydroxamic acid (SAHA), and
      other histone deacetylase inhibitors lead to a rapid release of free P-TEFb,
      followed by its reassembly into the 7SK snRNP. As a consequence, transcription of
      HEXIM1, a critical 7SK snRNP subunit, and HIV is induced. In this study, we found
      that a bromodomain and extra-terminal (BET) bromodomain inhibitor, JQ1, which
      inhibits BRD4 by blocking its association with chromatin, also leads to the rapid
      release of free P-TEFb from the 7SK snRNP. Indeed, JQ1 transiently increased
      levels of free P-TEFb and BRD4.P-TEFb and SEC.P-TEFb complexes in cells. As a
      consequence, the levels of HEXIM1 and HIV proteins rose. Importantly, the
      knockdown of ELL2, a subunit of the SEC, blocked the ability of JQ1 to increase
      HIV transcription. Finally, the effects of JQ1 and HMBA or SAHA on the P-TEFb
      equilibrium were cooperative. We conclude that HMBA, SAHA, and JQ1 affect
      transcription elongation by a similar and convergent mechanism.

PMID- 22952230
TI  - The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold
      symmetry.
AB  - The sigma-1 receptor (Sig1R) is up-regulated in many human tumors and plays a
      role in the control of cancer cell proliferation and invasiveness. At the
      molecular level, the Sig1R modulates the activity of various ion channels,
      apparently through a direct interaction. We have previously shown using atomic
      force microscopy imaging that the Sig1R binds to the trimeric acid-sensing ion
      channel 1A with 3-fold symmetry. Here, we investigated the interaction between
      the Sig1R and the Nav1.5 voltage-gated Na(+) channel, which has also been
      implicated in promoting the invasiveness of cancer cells. We show that the Sig1R
      and Nav1.5 can be co-isolated from co-transfected cells, consistent with an
      intimate association between the two proteins. Atomic force microscopy imaging of
      the co-isolated proteins revealed complexes in which Nav1.5 was decorated by
      Sig1Rs. Frequency distributions of angles between pairs of bound Sig1Rs had two
      peaks, at ~90 degrees  and ~180 degrees , and the 90 degrees  peak was about
      twice the size of the 180 degrees  peak. These results demonstrate that the Sig1R
      binds to Nav1.5 with 4-fold symmetry. Hence, each set of six transmembrane
      regions in Nav1.5 likely constitutes a Sig1R binding site, suggesting that the
      Sig1R interacts with the transmembrane regions of its partners. Interestingly,
      two known Sig1R ligands, haloperidol and (+)-pentazocine, disrupted the
      Nav1.5/Sig1R interaction both in vitro and in living cells. Finally, we show that
      endogenously expressed Sig1R and Nav1.5 also functionally interact.

PMID- 22952231
TI  - T-cell receptor-optimized peptide skewing of the T-cell repertoire can enhance
      antigen targeting.
AB  - Altered peptide antigens that enhance T-cell immunogenicity have been used to
      improve peptide-based vaccination for a range of diseases. Although this strategy
      can prime T-cell responses of greater magnitude, the efficacy of constituent T
      cell clonotypes within the primed population can be poor. To overcome this
      limitation, we isolated a CD8(+) T-cell clone (MEL5) with an enhanced ability to
      recognize the HLA A*0201-Melan A(27-35) (HLA A*0201-AAGIGILTV) antigen expressed
      on the surface of malignant melanoma cells. We used combinatorial peptide library
      screening to design an optimal peptide sequence that enhanced functional
      activation of the MEL5 clone, but not other CD8(+) T-cell clones that recognized
      HLA A*0201-AAGIGILTV poorly. Structural analysis revealed the potential for new
      contacts between the MEL5 T-cell receptor and the optimized peptide. Furthermore,
      the optimized peptide was able to prime CD8(+) T-cell populations in peripheral
      blood mononuclear cell isolates from multiple HLA A*0201(+) individuals that were
      capable of efficient HLA A*0201(+) melanoma cell destruction. This proof-of
      concept study demonstrates that it is possible to design altered peptide antigens
      for the selection of superior T-cell clonotypes with enhanced antigen recognition
      properties.

PMID- 22952232
TI  - Genome-wide epigenetic data facilitate understanding of disease susceptibility
      association studies.
AB  - Complex traits such as susceptibility to diseases are determined in part by
      variants at multiple genetic loci. Genome-wide association studies can identify
      these loci, but most phenotype-associated variants lie distal to protein-coding
      regions and are likely involved in regulating gene expression. Understanding how
      these genetic variants affect complex traits depends on the ability to predict
      and test the function of the genomic elements harboring them. Community efforts
      such as the ENCODE Project provide a wealth of data about epigenetic features
      associated with gene regulation. These data enable the prediction of testable
      functions for many phenotype-associated variants.

PMID- 22952233
TI  - Phosphorylation of serine 51 regulates the interaction of human DNA ligase I with
      replication factor C and its participation in DNA replication and repair.
AB  - Human DNA ligase I (hLigI) joins Okazaki fragments during DNA replication and
      completes excision repair via interactions with proliferating cell nuclear
      antigen and replication factor C (RFC). Unlike proliferating cell nuclear
      antigen, the interaction with RFC is regulated by hLigI phosphorylation. To
      identity of the site(s) involved in this regulation, we analyzed phosphorylated
      hLigI purified from insect cells by mass spectrometry. These results suggested
      that serine 51 phosphorylation negatively regulates the interaction with RFC.
      Therefore, we constructed versions of hLigI in which serine 51 was replaced with
      either alanine (hLigI51A) to prevent phosphorylation or aspartic acid (hLigI51D)
      to mimic phosphorylation. hLigI51D but not hLigI51A was defective in binding to
      purified RFC and in associating with RFC in cell extracts. Although DNA synthesis
      and proliferation of hLigI-deficient cells expressing either hLig51A or hLig51
      was reduced compared with cells expressing wild-type hLigI, cellular senescence
      was only observed in the cells expressing hLigI51D. Notably, these cells had
      increased levels of spontaneous DNA damage and phosphorylated CHK2. In addition,
      although expression of hLigI51A complemented the sensitivity of hLigI-deficient
      cells to a poly (ADP-ribose polymerase (PARP) inhibitor, expression of hLig151D
      did not, presumably because these cells are more dependent upon PARP-dependent
      repair pathways to repair the damage resulting from the abnormal DNA replication.
      Finally, neither expression of hLigI51D nor hLigI51A fully complemented the
      sensitivity of hLigI-deficient cells to DNA alkylation. Thus, phosphorylation of
      serine 51 on hLigI plays a critical role in regulating the interaction between
      hLigI and RFC, which is required for efficient DNA replication and repair.

PMID- 22952234
TI  - Crystal structures of the scaffolding protein LGN reveal the general mechanism by
      which GoLoco binding motifs inhibit the release of GDP from Galphai.
AB  - GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to
      Galpha subunit and acting as guanine nucleotide dissociation inhibitors. GLs of
      LGN are also known to bind the GDP form of Galpha(i/o) during asymmetric cell
      division. Here, we show that the C-terminal GL domain of LGN binds four molecules
      of Galpha(i).GDP. The crystal structures of Galpha(i).GDP in complex with LGN GL3
      and GL4, respectively, reveal distinct GL/Galpha(i) interaction features when
      compared with the only high resolution structure known with GL/Galpha(i)
      interaction between RGS14 and Galpha(i1.) Only a few residues C-terminal to the
      conserved GL sequence are required for LGN GLs to bind to Galpha(i).GDP. A highly
      conserved "double Arg finger" sequence (RPsi(D/E)(D/E)QR) is responsible for LGN
      GL to bind to GDP bound to Galpha(i). Together with the sequence alignment, we
      suggest that the LGN GL/Galpha(i) interaction represents a general binding mode
      between GL motifs and Galpha(i). We also show that LGN GLs are potent guanine
      nucleotide dissociation inhibitors.

PMID- 22952235
TI  - Fatty acids change the conformation of uncoupling protein 1 (UCP1).
AB  - UCP1 catalyzes proton leak across the mitochondrial inner membrane to disengage
      substrate oxidation from ATP production. It is well established that UCP1 is
      activated by fatty acids and inhibited by purine nucleotides, but precisely how
      this regulation occurs remains unsettled. Although fatty acids can competitively
      overcome nucleotide inhibition in functional assays, fatty acids have little
      effect on purine nucleotide binding. Here, we present the first demonstration
      that fatty acids induce a conformational change in UCP1. Palmitate dramatically
      changed the binding kinetics of 2'/3'-O-(N-methylanthraniloyl)-GDP, a
      fluorescently labeled nucleotide analog, for UCP1. Furthermore, palmitate
      accelerated the rate of enzymatic proteolysis of UCP1. The altered kinetics of
      both processes indicate that fatty acids change the conformation of UCP1,
      reconciling the apparent discrepancy between existing functional and ligand
      binding data. Our results provide a framework for how fatty acids and nucleotides
      compete to regulate the activity of UCP1.

PMID- 22952236
TI  - Transforming growth factor beta suppresses osteoblast differentiation via the
      vimentin activating transcription factor 4 (ATF4) axis.
AB  - ATF4 is an osteoblast-enriched transcription factor of the leucine zipper family.
      We recently identified that vimentin, a leucine zipper-containing intermediate
      filament protein, suppresses ATF4-dependent osteocalcin (Ocn) transcription and
      osteoblast differentiation. Here we show that TGFbeta inhibits ATF4-dependent
      activation of Ocn by up-regulation of vimentin expression. Osteoblasts lacking
      Atf4 (Atf4(-/-)) were less sensitive than wild-type (WT) cells to the inhibition
      by TGFbeta on alkaline phosphatase activity, Ocn transcription and
      mineralization. Importantly, the anabolic effect of a monoclonal antibody
      neutralizing active TGFbeta ligands on bone in WT mice was blunted in Atf4(-/-)
      mice. These data establish that ATF4 is required for TGFbeta-related suppression
      of Ocn transcription and osteoblast differentiation in vitro and in vivo.
      Interestingly, TGFbeta did not directly regulate the expression of ATF4; instead,
      it enhanced the expression of vimentin, a negative regulator of ATF4, at the post
      transcriptional level. Accordingly, knockdown of endogenous vimentin in 2T3
      osteoblasts abolished the inhibition of Ocn transcription by TGFbeta, confirming
      an indirect mechanism by which TGFbeta acts through vimentin to suppress ATF4
      dependent Ocn activation. Furthermore, inhibition of PI3K/Akt/mTOR signaling, but
      not canonical Smad signaling, downstream of TGFbeta, blocked TGFbeta-induced
      synthesis of vimentin, and inhibited ATF4-dependent Ocn transcription in
      osteoblasts. Thus, our study identifies that TGFbeta stimulates vimentin
      production via PI3K-Akt-mTOR signaling, which leads to suppression of ATF4
      dependent Ocn transcription and osteoblast differentiation.

PMID- 22952237
TI  - Genome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight
      into chromatin structure and regulation.
AB  - Eukaryotic genomes are organized into higher order chromatin architectures by
      protein-mediated long-range interactions in the nucleus. CCCTC-binding factor
      (CTCF), a sequence-specific transcription factor, serves as a chromatin organizer
      in building this complex chromatin structure by linking chromosomal domains.
      Recent genome-wide studies mapping the binding sites of CTCF and its interacting
      partner, cohesin, using chromatin immunoprecipitation coupled with deep
      sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin.
      This partnership between CTCF and cohesin is emerging as a novel and perhaps
      pivotal aspect of gene regulatory mechanisms, in addition to playing a role in
      the organization of higher order chromatin architecture.

PMID- 22952238
TI  - Uncovering transcription factor modules using one- and three-dimensional
      analyses.
AB  - Transcriptional regulation is a critical mediator of many normal cellular
      processes, as well as disease progression. Transcription factors (TFs) often co
      localize at cis-regulatory elements on the DNA, form protein complexes, and
      collaboratively regulate gene expression. Machine learning and Bayesian
      approaches have been used to identify TF modules in a one-dimensional context.
      However, recent studies using high throughput technologies have shown that TF
      interactions should also be considered in three-dimensional nuclear space. Here,
      we describe methods for identifying TF modules and discuss how moving from a one
      dimensional to a three-dimensional paradigm, along with integrated experimental
      and computational approaches, can lead to a better understanding of TF
      association networks.

PMID- 22952239
TI  - Transcription factor-mediated epigenetic reprogramming.
AB  - Input from various signaling pathways in conjunction with specific transcription
      factors (TFs), noncoding RNAs, and epigenetic modifiers governs the maintenance
      of cellular identity. Endogenous or exogenous TFs operate within certain
      boundaries, which are set, in part, by the cell type-specific epigenetic
      landscape. Ectopic expression of selected TFs can override the cellular identity
      and induce reprogramming to alternative fates. In this minireview, we summarize
      many of the classic examples and a large number of recent studies that have taken
      advantage of TF-mediated reprogramming to produce cell types of biomedical
      relevance.

PMID- 22952240
TI  - SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions.
AB  - Chromatin-remodeling enzymes play essential roles in many biological processes,
      including gene expression, DNA replication and repair, and cell division.
      Although one such complex, SWI/SNF, has been extensively studied, new discoveries
      are still being made. Here, we review SWI/SNF biochemistry; highlight recent
      genomic and proteomic advances; and address the role of SWI/SNF in human
      diseases, including cancer and viral infections. These studies have greatly
      increased our understanding of complex nuclear processes.

PMID- 22952242
TI  - Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal
      transduction through direct binding to phosphorylated tyrosines 591 and 919 of
      Flt3.
AB  - The receptor tyrosine kinase Flt3 is an important growth factor receptor in
      hematopoiesis, and gain-of-function mutations of the receptor contribute to the
      transformation of acute myeloid leukemia. SOCS6 (suppressor of cytokine signaling
      6) is a member of the SOCS family of E3 ubiquitin ligases that can regulate
      receptor tyrosine kinase signal transduction. In this study, we analyzed the role
      of SOCS6 in Flt3 signal transduction. The results show that ligand stimulation of
      Flt3 can induce association of SOCS6 and Flt3 and tyrosine phosphorylation of
      SOCS6. Phosphopeptide fishing indicated that SOCS6 binds directly to
      phosphotyrosines 591 and 919 of Flt3. By using stably transfected Ba/F3 cells
      with Flt3 and/or SOCS6, we show that the presence of SOCS6 can enhance
      ubiquitination of Flt3, as well as internalization and degradation of the
      receptor. The presence of SOCS6 also induces weaker activation of Erk1/2, but not
      Akt, in transfected Ba/F3 and UT-7 cells and in OCI-AML-5 cells. The absence of
      SOCS6 promotes Ba/F3 and UT-7 cell proliferation induced by oncogenic internal
      tandem duplications of Flt3. Taken together, these results suggest that SOCS6
      negatively regulates Flt3 activation, the downstream Erk signaling pathway, and
      cell proliferation.

PMID- 22952243
TI  - Mycobacterium smegmatis Lsr2 physically and functionally interacts with a new
      flavoprotein involved in bacterial resistance to oxidative stress.
AB  - Lsr2, a bacterial histone-like protein, has been shown to be clearly involved in
      modulating chromatin organization, compaction and global gene expression.
      However, the regulatory mechanism of its functions remains largely unclear. In
      this study, using bacterial two-hybrid technique and pull-down assays, the
      Mycobacterium smegmatis Lsr2 was detected to associate with a hypothetical
      flavoprotein, Ms4334. A further co-immunoprecipitation assay confirmed the
      physical interaction between these two proteins in vivo in mycobacteria.
      Importantly, the Ms4334 protein was also capable of enhancing the inhibitory
      effect of Lsr2 in vitro on the function of DNA topoisomerase I (MsTopA).
      Therefore, Lsr2 could physically and functionally interact with Ms4334. Further,
      the Ms4334 gene was confirmed to encode a new FAD-binding flavoprotein that
      displayed two characteristic absorption peaks at about 370 and 450 nm in a UV
      visible spectra scanning assay. Interestingly, when comparing the growths of wild
      type M. smegmatis with the Ms4334-knockout strain in response to H(2)O(2), Ms4334
      was found to contribute to mycobacterial resistance to oxidative stress. The
      findings provided important clues for a further understanding of the regulation
      mechanism of Lsr2 in mycobacteria.

PMID- 22952241
TI  - The chromatin fingerprint of gene enhancer elements.
AB  - Different cell types within a single organism are generally distinguished by
      strikingly different patterns of gene expression, which are dynamic throughout
      development and adult life. Distal enhancer elements are key drivers of
      spatiotemporal specificity in gene regulation. Often located tens of kilobases
      from their target promoters and functioning in an orientation-independent manner,
      the identification of bona fide enhancers has proved a formidable challenge. With
      the development of ChIP-seq, global cataloging of putative enhancers has become
      feasible. Here, we review the current understanding of the chromatin landscape at
      enhancers and how these chromatin features enable robust identification of tissue
      specific enhancers.

PMID- 22952244
TI  - Should we stop testing for asymptomatic carotid atherosclerosis?

PMID- 22952246
TI  - Response from the SAMMPRIS trial principal investigators regarding inaccuracies
      in this editorial.

PMID- 22952245
TI  - Inflammation as a predictor for delayed cerebral ischemia after aneurysmal
      subarachnoid haemorrhage.
AB  - BACKGROUND: The mechanism of development of delayed cerebral ischemia (DCI) after
      aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Inflammatory
      processes are implicated in the development of ischemic stroke and may also
      predispose to the development of DCI following SAH. The objective of this study
      was to test whether concentrations of circulating inflammatory markers (C
      reactive protein (CRP), interleukin-6 (IL-6) and interleukin 1 receptor
      antagonist (IL-1Ra)) were predictive for DCI following SAH. Secondary analyses
      considered white cell count (WCC) and erythrocyte sedimentation rate (ESR).
      METHODS: This was a single-center case-control study nested within a prospective
      cohort. Plasma inflammatory markers were measured in patients up to 15 days after
      SAH (initial, peak, average, final and rate of change to final). Cases were
      defined as those developing DCI. Inflammatory markers were compared between cases
      and randomly selected matched controls. RESULTS: Among the 179 participants there
      were 46 cases of DCI (26%). In primary analyses the rate of change of IL-6 was
      associated with DCI (OR 2.3 (95% CI 1.1 to 5.0); p=0.03). The final value and
      rate of change of WCC were associated with DCI (OR 1.2 (95% CI 1.0 to 1.3) and OR
      1.3 (95% CI 1.0 to 1.6), respectively). High values of ESR were associated with
      DCI (OR 2.4 (95% CI 1.3 to 4.6) initial; OR 2.3 (95% CI 1.3 to 4.2) average; OR
      2.1 (95% CI 1.1 to 3.9) peak; and OR 2.0 (95% CI 1.2 to 3.3) final value).
      CONCLUSIONS: Leucocytosis and change in IL-6 prior to DCI reflect impending
      cerebral ischemia. The time-independent association of ESR with DCI after SAH may
      identify this as a risk factor. These data suggest that systemic inflammatory
      mechanisms may increase the susceptibility to the development of DCI after SAH.

PMID- 22952247
TI  - The sea anchor technique: a novel method to aid in stent-assisted embolization of
      giant cerebral aneurysms.
AB  - Endovascular navigation past some large or giant intracranial aneurysms for the
      purpose of stent deployment can be difficult. Some of these lesions have a
      morphology which compels the operator to navigate through the aneurysm dome in
      order to gain distal access, a step which requires straightening of the delivery
      microcatheter before a stent can be deployed. In most patients this can be
      achieved by simply retracting the microcatheter and reducing the loop within the
      aneurysm. However, in certain patients the acute angle formed between aneurysm
      inflow and outflow tracts as well as the dynamics of tension within the
      microcatheter act together to prevent this from happening. Instead of retracting
      and straightening across the aneurysm neck, the microcatheter withdraws leaving
      the intra-aneurysm loop intact. This challenge can thwart attempts at stent
      placement and subsequent embolization. The authors describe a simple and safe
      technique to circumvent this problem, a way of stabilizing the distal tip of the
      microcatheter which they term the 'sea anchor'. 

PMID- 22952248
TI  - Patient selection, physician experience and antiplatelet therapy testing are
      critical.

PMID- 22952249
TI  - VvGOLS1 and VvHsfA2 are involved in the heat stress responses in grapevine
      berries.
AB  - Among various environmental factors, temperature is a major regulator affecting
      plant growth, development and fruit composition. Grapevine is the most cultivated
      fruit plant throughout the world, and grapes are used for wine production and
      human consumption. The molecular mechanisms involved in grapevine tolerance to
      high temperature, especially at the fruit level, are poorly understood. To better
      characterize the sensitivity of berries to the microenvironment, high temperature
      conditions were locally applied to Vitis vinifera Cabernet Sauvignon clusters.
      Two genes, VvGOLS1 and VvHsfA2, up-regulated by this treatment, were identified
      and further characterized. The expression profile of VvGOLS1 correlated
      positively with galactinol accumulation in heat-stressed berries. However, no
      galactinol derivatives, such as raffinose and stachyose, accumulated upon heat
      stress. Heterologous expression of VvGOLS1 in Escherichia coli showed that it
      encodes a functional galactinol synthase. Transient expression assays showed that
      the heat stress factor VvHsfA2 transactivates the promoter of VvGOLS1 in a heat
      stress-dependent manner. Taken together, our results highlight the intrinsic
      capacity of grape berries to perceive heat stress and to initiate adaptive
      responses, suggesting that galactinol may play a signaling role in these
      responses.

PMID- 22952250
TI  - Enhancement of non-photochemical quenching in the Bryophyte Physcomitrella patens
      during acclimation to salt and osmotic stress.
AB  - Drought and salt stress are major abiotic constraints affecting plant growth
      worldwide. Under these conditions, the production of reactive oxygen species
      (ROS) is a common phenomenon taking place mainly in chloroplasts, peroxisomes,
      mitochondria and apoplasts, especially when associated with high light stress.
      ROS are harmful because of their high reactivity to cell components, thereby
      leading to cytotoxicity and cell death. During the Ordovician and early Devonian
      period, photosynthetic organisms colonized terrestrial habitats, and the
      acquisition of desiccation tolerance has been a major component of their
      evolution. We have studied the capacity for acclimation to drought and salt
      stress of the moss Physcomitrella patens, a representative of the early land
      colonization stage. Exposure to high concentrations of NaCl and sorbitol strongly
      affects chloroplast development, the Chl content and the thylakoid protein
      composition in this moss. Under sublethal conditions (0.2 M NaCl and 0.4 M
      sorbitol), the photosynthetic apparatus of P. patens responds to oxidative stress
      by increasing non-photochemical quenching (NPQ). Surprisingly, the accumulation
      of PSBS and LHCSR, the two polypeptides essential for NPQ in P. patens, was not
      up-regulated in these conditions. Rather, an increased NPQ amplitude correlated
      with the overaccumulation of zeaxanthin and the presence of the enzyme
      violaxanthin de-epoxidase. These results suggest that the regulation of excess
      energy dissipation through control of PSBS and LHCSR is mainly driven by light
      conditions, while osmotic and salt stress act through acclimative regulation of
      the xanthophyll cycle. We conclude that regulation of the xanthophyll cycle is an
      important anticipatory strategy against photoinhibition by high light.

PMID- 22952252
TI  - The importance of studying personality in individuals with congenital heart
      disease.

PMID- 22952251
TI  - Copper transport and compartmentation in grape cells.
AB  - Copper-based fungicides have been widely used against several grapevine (Vitis
      vinifera L.) diseases since the late 1800s when the Bordeaux mixture was
      developed, but their intensive use has raised phytotoxicity concerns. In this
      study, physiological, biochemical and molecular approaches were combined to
      investigate the impacts of copper in grape cells and how it is transported and
      compartmented intracellularly. Copper reduced the growth and viability of grape
      cells (CSB, Cabernet Sauvignon Berry) in a dose-dependent manner above 100 uM and
      was accumulated in specific metal ion sinks. The copper-sensitive probe Phen
      Green SK was used to characterize copper transport across the plasma membrane of
      CSB cells. The transport system (K(m) = 583 uM; V(max) = 177 * 10(-6) %DeltaF
      min(-1) protoplast(-1)) was regulated by copper availability in the culture
      medium, stimulated by Ca(2+) and inhibited by Zn(2+). The pH-sensitive
      fluorescent probe ACMA (9-amino-6-chloro-2-methoxyacridine) was used to evaluate
      the involvement of proton-dependent copper transport across the tonoplast. Cu(2+)
      compartmentation in the vacuole was dependent on the transmembrane pH gradient
      generated by both V-H(+)-ATPase and V-H(+)-pyrophosphatase (PPase). High copper
      levels in the growth medium did not affect the activity of V-H(+)-PPase but
      decreased the magnitude of the H(+) gradient generated by V-H(+)-ATPase.
      Expression studies of VvCTr genes showed that VvCTr1 and VvCTr8 were distinctly
      affected by CuSO(4) availability in grape cell cultures and that both genes were
      highly expressed in the green stage of grape berries.

PMID- 22952254
TI  - Making do with what we have: use your bootstraps.

PMID- 22952253
TI  - Prior starvation mitigates acute doxorubicin cardiotoxicity through restoration
      of autophagy in affected cardiomyocytes.
AB  - AIMS: Active autophagy has recently been reported in doxorubicin-induced
      cardiotoxicity; here we investigated its pathophysiological role. METHODS AND
      RESULTS: Acute cardiotoxicity was induced in green fluorescent protein
      microtubule-associated protein 1 light chain 3 (GFP-LC3) transgenic mice by
      administering two intraperitoneal injections of 10 mg/kg doxorubicin with a 3 day
      interval. A starvation group was deprived of food for 48 h before each injection
      to induce autophagy in advance. Doxorubicin treatment caused left ventricular
      dilatation and dysfunction within 6 days. Cardiomyocyte autophagy appeared to be
      activated in the doxorubicin group, based on LC3, p62, and cathepsin D
      expression, while it seemed somewhat diminished by starvation prior to
      doxorubicin treatment. Unexpectedly, however, myocardial ATP levels were reduced
      in the doxorubicin group, and this reduction was prevented by earlier starvation.
      Electron microscopy revealed that the autophagic process was indeed initiated in
      the doxorubicin group, as shown by the increased lysosomes, but was not
      completed, i.e. autophagolysosome formation was rare. Starvation prior to
      doxorubicin treatment partly restored autophagosome formation towards control
      levels. Autophagic flux assays in both in vivo and in vitro models confirmed that
      doxorubicin impairs completion of the autophagic process in cardiomyocytes. The
      activities of both AMP-activated protein kinase and the autophagy-initiating
      kinase unc-51-like kinase 1 (ULK1) were found to be decreased by doxorubicin, and
      these were restored by prior starvation. CONCLUSION: Prior starvation mitigates
      acute doxorubicin cardiotoxicity; the underlying mechanism may be, at least in
      part, restoration and further augmentation of myocardial autophagy, which is
      impaired by doxorubicin, probably through inactivation of AMP-activated protein
      kinase and ULK1.

PMID- 22952255
TI  - Explorations in statistics: permutation methods.
AB  - Learning about statistics is a lot like learning about science: the learning is
      more meaningful if you can actively explore. This eighth installment of
      Explorations in Statistics explores permutation methods, empiric procedures we
      can use to assess an experimental result-to test a null hypothesis-when we are
      reluctant to trust statistical theory alone. Permutation methods operate on the
      observations-the data-we get from an experiment. A permutation procedure answers
      this question: out of all the possible ways we can rearrange the observations we
      got, in what proportion of those arrangements is the sample statistic we care
      about at least as extreme as the one we got? The answer to that question is the P
      value.

PMID- 22952256
TI  - Assessing formal teaching of ethics in physiology: an empirical survey, patterns,
      and recommendations.
AB  - Ethics should be an important component of physiological education. In this
      report, we examined to what extent teaching of ethics is formally being
      incorporated into the physiology curriculum. We carried out an e-mail survey in
      which we asked the e-mail recipients whether their institution offered a course
      or lecture on ethics as part of the physiology teaching process at their
      institution, using the following query: "We are now doing an online survey in
      which we would like to know whether you offer a course or a lecture on ethics as
      part of your physiology teaching curriculum." The response rate was 53.3%: we
      received 104 responses of a total of 195 sent out. Our responses came from 45
      countries. While all of our responders confirmed that there was a need for ethics
      during medical education and scientific training, the degree of inclusion of
      formal ethics in the physiology curriculum varied widely. Our survey showed that,
      in most cases (69%), including at our Medical University of Graz, ethics in
      physiology is not incorporated into the physiology curriculum. Given this result,
      we suggest specific topics related to ethics and ethical considerations that
      could be integrated into the physiology curriculum. We present here a template
      example of a lecture "Teaching Ethics in Physiology" (structure, content,
      examples, and references), which was based on guidelines and case reports
      provided by experts in this area (e.g., Benos DJ. Ethics revisited. Adv Physiol
      Educ 25: 189-190, 2001). This lecture, which we are presently using in Graz,
      could be used as a base that could lead to greater awareness of important ethical
      issues in students at an early point in the educational process.

PMID- 22952257
TI  - Can medical students teach? A near-peer-led teaching program for year 1 students.
AB  - The General Medical Council states that United Kingdom graduates must function
      effectively as educators. There is a growing body of evidence showing that
      medical students can be included as teachers within a medical curriculum. Our aim
      was to design and implement a near-peer-led teaching program in an undergraduate
      medical curriculum and assess its acceptability among year 1 students. Students
      received six tutorials focusing on aspects of cardiac, respiratory, and blood
      physiology. Tutorials ran alongside standard module teaching. Students were
      taught in groups of ~30 students/group, and an active teaching approach was used
      in sessions where possible. Using anonymous evaluations, student feedback was
      collected for the program overall and for each tutorial. The program was
      voluntary and open to all first-year students, and 94 (of 138) medical students
      from year 1 at Brighton and Sussex Medical School were recruited to the study.
      The tutorial program was popular among students and was well attended throughout.
      Individual tutorial and overall program quantitative and qualitative feedback
      showed that students found the tutorials very useful in consolidating material
      taught within the module. Students found the small group and active teaching
      style of the near-peer tutors very useful to facilitating their learning
      experience. The end-of-module written examination scores suggest that the
      tutorials may have had a positive effect on student outcome compared with
      previous student attainment. In conclusion, the present study shows that a near
      peer tutorial program can be successfully integrated into a teaching curriculum.
      The feedback demonstrates that year 1 students are both receptive and find the
      additional teaching of benefit.

PMID- 22952258
TI  - Use of concept mapping in an undergraduate introductory exercise physiology
      course.
AB  - Physiology is often considered a challenging course for students. It is up to
      teachers to structure courses and create learning opportunities that will
      increase the chance of student success. In an undergraduate exercise physiology
      course, concept maps are assigned to help students actively process and organize
      information into manageable and meaningful chunks and to teach them to recognize
      the patterns and regularities of physiology. Students are first introduced to
      concept mapping with a commonly relatable nonphysiology concept and are then
      assigned a series of maps that become more and more complex. Students map the
      acute response to a drop in blood pressure, the causes of the acute increase in
      stroke volume during cardiorespiratory exercise, and the factors contributing to
      an increase in maximal O(2) consumption with cardiorespiratory endurance
      training. In the process, students draw the integrative nature of physiology,
      identify causal relationships, and learn about general models and core principles
      of physiology.

PMID- 22952259
TI  - How much structuring is beneficial with regard to examination scores? A
      prospective study of three forms of active learning.
AB  - Many studies have demonstrated a superiority of active learning forms compared
      with traditional lecture. However, there is still debate as to what degree
      structuring is necessary with regard to high exam outcomes. Seventy-five students
      from a premedical school were randomly attributed to an active lecture group, a
      cooperative group, or a collaborative learning group. The active lecture group
      received lectures with questions to resolve at the end of the lecture. At the
      same time, the cooperative group and the collaborative group had to work on a
      problem and prepare presentations for their answers. The collaborative group
      worked in a mostly self-directed manner; the cooperative group had to follow a
      time schedule. For the additional work of preparing the poster presentation, the
      collaborative and cooperative groups were allowed 50% more working time. In part
      1, all groups worked on the citric acid cycle, and in part 2, all groups worked
      on molecular genetics. Collaborative groups had to work on tasks and prepare
      presentations for their answers. At the end of each part, all three groups were
      subjected to the same exam. Additionally, in the collaborative and cooperative
      groups, the presentations were marked. All evaluations were performed by two
      independent examiners. Exam results of the active lecture groups were highest.
      Results of the cooperative group were nonsignificantly lower than the active
      lecture group and significantly higher than the collaborative group. The
      presentation quality was nonsignificantly higher in the collaborative group
      compared with the cooperative group. This study shows that active lecturing
      produced the highest exam results, which significantly differed from
      collaborative learning results. The additional elaboration in the cooperative and
      collaborative learning setting yielded the high presentation quality but
      apparently could not contribute further to exam scores. Cooperative learning
      seems to be a good compromise if high exam and presentation scores are expected.

PMID- 22952260
TI  - Using a high-fidelity patient simulator with first-year medical students to
      facilitate learning of cardiovascular function curves.
AB  - Students are relying on technology for learning more than ever, and educators
      need to adapt to facilitate student learning. High-fidelity patient simulators
      (HFPS) are usually reserved for the clinical years of medical education and are
      geared to improve clinical decision skills, teamwork, and patient safety. Finding
      ways to incorporate HFPS into preclinical medical education represents more of a
      challenge, and there is limited literature regarding its implementation. The main
      objective of this study was to implement a HFPS activity into a problem-based
      curriculum to enhance the learning of basic sciences. More specifically, the
      focus was to aid in student learning of cardiovascular function curves and help
      students develop heart failure treatment strategies based on basic cardiovascular
      physiology concepts. Pretests and posttests, along with student surveys, were
      used to determine student knowledge and perception of learning in two first-year
      medical school classes. There was an increase of 21% and 22% in the percentage of
      students achieving correct answers on a posttest compared with their pretest
      score. The median number of correct questions increased from pretest scores of 2
      and 2.5 to posttest scores of 4 and 5 of a possible total of 6 in each respective
      year. Student survey data showed agreement that the activity aided in learning.
      This study suggests that a HFPS activity can be implemented during the
      preclinical years of medical education to address basic science concepts.
      Additionally, it suggests that student learning of cardiovascular function curves
      and heart failure strategies are facilitated.

PMID- 22952261
TI  - The Lateralizer: a tool for students to explore the divided brain.
AB  - Despite a profusion of popular misinformation about the left brain and right
      brain, there are functional differences between the left and right cerebral
      hemispheres in humans. Evidence from split-brain patients, individuals with
      unilateral brain damage, and neuroimaging studies suggest that each hemisphere
      may be specialized for certain cognitive processes. One way to easily explore
      these hemispheric asymmetries is with the divided visual field technique, where
      visual stimuli are presented on either the left or right side of the visual field
      and task performance is compared between these two conditions; any behavioral
      differences between the left and right visual fields may be interpreted as
      evidence for functional asymmetries between the left and right cerebral
      hemispheres. We developed a simple software package that implements the divided
      visual field technique, called the Lateralizer, and introduced this experimental
      approach as a problem-based learning module in a lower-division research methods
      course. Second-year undergraduate students used the Lateralizer to experimentally
      challenge and explore theories of the differences between the left and right
      cerebral hemispheres. Measured learning outcomes after active exploration with
      the Lateralizer, including new knowledge of brain anatomy and connectivity, were
      on par with those observed in an upper-division lecture course. Moreover, the
      project added to the students' research skill sets and seemed to foster an
      appreciation of the link between brain anatomy and function.

PMID- 22952262
TI  - Overcoming misconceptions in neurophysiology learning: an approach using color
      coded animations.

PMID- 22952263
TI  - Misconceptions highlighted among medical students in the annual International
      Intermedical School Physiology Quiz.

PMID- 22952264
TI  - Multilocus variable-number tandem-repeat analysis of Mycoplasma pneumoniae
      clinical isolates from 1962 to the present: a retrospective study.
AB  - In this study, we evaluated a recently developed multilocus variable-number
      tandem-repeat (VNTR) analysis (MLVA) method for the molecular typing of
      Mycoplasma pneumoniae. The method is based on GeneScan analysis of five VNTR loci
      throughout the genome which define a specific genotype based on the number of
      tandem repeats within each locus. A retrospective analysis of 154 M. pneumoniae
      clinical isolates collected over the last 50 years and a limited (n = 4) number
      of M. pneumoniae-positive primary specimens acquired by the CDC was performed
      using MLVA. Eighteen distinct VNTR types were identified, including two
      previously unidentified VNTR types. Isolates from several M. pneumoniae community
      outbreaks within the United States were also analyzed to examine clonality of a
      specific MLVA type. Observed in vitro variability of the Mpn1 VNTR locus prompted
      further analysis, which showed multiple insertions or deletions of tandem repeats
      within this locus for a number of specimens and isolates. To our knowledge, this
      is the first report showing variation within the Mpn1 locus, thus affecting
      precise and reliable classification using the current MLVA typing system. The
      superior discriminatory capability of MLVA provides a powerful tool for greater
      resolution of M. pneumoniae strains and could be useful during outbreaks and
      epidemiological investigations.

PMID- 22952265
TI  - Ten years of external quality assessment of human immunodeficiency virus type 1
      RNA quantification.
AB  - Viral load testing is an essential parameter in guiding antiretroviral therapy
      for individuals infected with human immunodeficiency virus type 1 (HIV-1). An
      external quality assessment scheme for the molecular quantification of HIV-1 RNA
      was introduced by the United Kingdom National External Quality Assessment Service
      for Microbiology in 2000. Specimen pairs of freeze-dried plasma were distributed
      to a median of 141 participants three times a year. The aim of this study was to
      analyze the quantification of HIV-1 RNA results between 2000 and 2010. Overall
      variability, measured by the standard deviations of all viral load results for
      each specimen, was below 0.5 log copy/ml (n = 48). When we compared assay
      results, the medians of the viral load by assay were within a range of 0.25 to
      1.08 log copies/ml, with the lowest median values being consistently reported
      with the Siemens branched-chain DNA assay. The spread of participant results and,
      hence, differences between assay medians were greater when quantifying non-B
      subtypes. Laboratories were scored on the proximity of their reported log
      difference for the specimen pair to the median log difference reported by all
      laboratories. The overall level of performance with the HIV-1 RNA specimens over
      the past 10 years has been consistently good, with more than 90% of the
      participants reporting in the accepted range (median difference, +/-0.5 log
      unit). Future distributions may result in tightening the acceptance levels of
      quantification and the use of more challenging specimens, including a variety of
      subtypes, with developments focusing on maintaining the clinical relevance and
      educational value of the scheme.

PMID- 22952266
TI  - Reclassification of the Candida haemulonii complex as Candida haemulonii (C.
      haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and
      C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic
      yeasts.
AB  - The Candida haemulonii species complex is currently known as C. haemulonii groups
      I and II. Here we describe C. haemulonii group II as a new species, Candida
      duobushaemulonii sp. nov., and C. haemulonii var. vulnera as new a variety of C.
      haemulonii group I using phenotypic and molecular methods. These taxa and other
      relatives of C. haemulonii (i.e., Candida auris and Candida pseudohaemulonii)
      cannot be differentiated by the commercial methods now used for yeast
      identification. Four isolates (C. haemulonii var. vulnera) differed from the
      other isolates of C. haemulonii in the sequence of the internal transcribed
      spacer (ITS) regions of the nuclear rRNA gene operon. The new species and the new
      variety have a multiresistant antifungal profile, which includes high MICs of
      amphotericin B (geometric mean MIC, 1.18 mg/liter for C. haemulonii var. vulnera
      and 2 mg/liter for C. duobushaemulonii sp. nov) and cross-resistance to azole
      compounds. Identification of these species should be based on molecular methods,
      such as sequence analysis of ITS regions and matrix-assisted laser desorption
      ionization-time of flight mass spectrometry.

PMID- 22952267
TI  - Accurate and rapid identification of Candida spp. frequently associated with
      fungemia by using PCR and the microarray-based Prove-it Sepsis assay.
AB  - The rapid identification of microbes responsible for bloodstream infections
      (BSIs) allows more focused and effective therapies and outcomes. DNA sequence
      based methods offer an opportunity for faster, accurate diagnosis and for
      effective therapy. As our objective of the study, the ability of the Prove-it
      Sepsis platform, already proven as a rapid PCR- and microarray-based assay for
      the majority of sepsis-causing bacteria, was extended to also rapidly identify
      clinically relevant yeasts in blood culture. The performance characteristics of
      this extended platform are described. We found that the extended diagnostic Prove
      it Sepsis platform was found to be highly accurate when analyzing primary
      isolates, spiked blood cultures, nucleic acid extracts from a retrospective blood
      culture data set, and primary blood cultures. Comparison of the blood culture
      results from the Prove-it Sepsis platform with those from conventional culture
      based methods or by gene sequencing demonstrated a sensitivity of 99% and a
      specificity of 98% for fungal targets (based on analysis of a total of 388
      specimens). Total assay time was 3 h from DNA extraction to BSI diagnosis. These
      results extend the performance characteristics of the Prove-it platform for
      bacteria to the easy, rapid, and accurate detection and species identification of
      yeasts in positive blood cultures. Incorporation of this extended and rapid
      diagnostic platform into the tools for clinical patient management would allow
      possibly faster identification and more focused therapies for BSIs.

PMID- 22952268
TI  - Diagnostic accuracy of PCR alone compared to galactomannan in bronchoalveolar
      lavage fluid for diagnosis of invasive pulmonary aspergillosis: a systematic
      review.
AB  - PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic
      criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic
      review assessing the diagnostic accuracy of PCR in BAL fluid with a direct
      comparison versus galactomannan (GM) in BAL fluid. We included prospective and
      retrospective cohort and case-control studies. Studies were included if they used
      the EORTC/MSG consensus definition criteria of IPA and assessed >=80% of patients
      at risk for IPA. Two reviewers abstracted data independently. Risk of bias was
      assessed using QUADAS-2. Summary sensitivity and specificity values were
      estimated using a bivariate model and reported with a 95% confidence interval
      (CI). Nineteen studies published between 1993 and 2012 were included. The summary
      sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA
      were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine
      cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for
      reference standard definitions, the summary sensitivity and specificity values
      (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively.
      Antifungal treatment before bronchoscopy significantly reduced sensitivity. The
      diagnostic performance of PCR was similar to that of GM in BAL fluid using an
      optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a
      positive result, the pooled sensitivity was higher than that of GM alone, with
      similar specificity. We conclude that the diagnostic performance of PCR in BAL
      fluid is good and comparable to that of GM in BAL fluid. Performing both tests
      results in optimal sensitivity with no loss of specificity. Results are dependent
      on the reference standard definitions.

PMID- 22952270
TI  - Comparison of BD GeneOhm Cdiff and Seegene Seeplex ACE PCR assays using toxigenic
      Clostridium difficile culture for direct detection of tcdB from stool specimens.
AB  - We evaluated the performances of 2 PCR assays (BD GeneOhm and Seegene ACE) for
      direct detection of tcdB from stool specimens. The concordance rate between BD
      and Seegene was 96.3%. The sensitivities, specificities, positive predictive
      values (PPVs), and negative predictive values (NPVs) of BD and Seegene were
      95.7%, 96.5%, 91.8%, and 98.2% and 90.0%, 97.1%, 92.6%, and 96.0%, respectively.

PMID- 22952269
TI  - Genetic diversity and population structure of Mycobacterium marinum: new insights
      into host and environmental specificities.
AB  - Mycobacterium marinum causes a systemic tuberculosis-like disease in fish and
      skin infections in humans that can spread to deeper structures, resulting in
      tenosynovitis, arthritis, and osteomyelitis. However, little information is
      available concerning (i) the intraspecific genetic diversity of M. marinum
      isolated from humans and animals; (ii) M. marinum genotype circulation in the
      different ecosystems, and (iii) the link between M. marinum genetic diversity and
      hosts (humans and fish). Here, we conducted a genetic study on 89 M. marinum
      isolates from humans (n = 68) and fish (n = 21) by using mycobacterial
      interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR)
      typing. The results show that the M. marinum population is genetically structured
      not only according to the host but also according to the ecosystem as well as to
      tissue tropism in humans. This suggests the existence of different genetic pools
      in the function of the biological and ecological compartments. Moreover, the
      presence of only certain M. marinum genotypes in humans suggests a different
      zoonotic potential of the M. marinum genotypes. Considering that the infection is
      linked to aquarium activity, a significant genetic difference was also detected
      when the human tissue tropism of M. marinum was taken into consideration, with a
      higher genetic polymorphism in strains isolated from patients with cutaneous
      forms than from individuals with deeper-structure infection. It appears that only
      few genotypes can produce deeper infections in humans, suggesting that the immune
      system might play a filtering role.

PMID- 22952271
TI  - Genetic evidence for the uncoupling of local aquaculture activities and a
      population of an invasive species--a case study of Pacific oysters (Crassostrea
      gigas).
AB  - Human-mediated introduction of nonnative species into coastal areas via
      aquaculture is one of the main pathways that can lead to biological invasions. To
      develop strategies to counteract invasions, it is critical to determine whether
      populations establishing in the wild are self-sustaining or based on repeated
      introductions. Invasions by the Pacific oyster (Crassostrea gigas) have been
      associated with the growing oyster aquaculture industry worldwide. In this study,
      temporal genetic variability of farmed and wild oysters from the largest enclosed
      bay in Ireland was assessed to reconstruct the recent biological history of the
      feral populations using 7 anonymous microsatellites and 7 microsatellites linked
      to expressed sequence tags (ESTs). There was no evidence of EST-linked markers
      showing footprints of selection. Allelic richness was higher in feral than in
      aquaculture samples (P = 0.003, paired t-test). Significant deviations from Hardy
      Weinberg equilibrium due to heterozygote deficiencies were detected for almost
      all loci and samples, most likely explained by the presence of null alleles.
      Relatively high genetic differentiation was found between aquaculture and feral
      oysters (largest pairwise multilocus F(ST) 0.074, P < 0.01) and between year
      classes of oysters from aquaculture (largest pairwise multilocus F(ST) 0.073, P <
      0.01), which was also confirmed by the strong separation of aquaculture and wild
      samples using Bayesian clustering approaches. A 10-fold higher effective
      population size (N(e)) and a high number of private alleles in wild oysters
      suggest an established self-sustaining feral population. The wild oyster
      population studied appears demographically independent from the current
      aquaculture activities in the estuary and alternative scenarios of introduction
      pathways are discussed.

PMID- 22952272
TI  - MHC diversity and mate choice in the magellanic penguin, Spheniscus magellanicus.
AB  - We estimated levels of diversity at the major histocompatibility complex (MHC)
      class II DRbeta1 gene in 50 breeding pairs of the Magellanic penguin and compared
      those to estimates from Humboldt and Galapagos penguins. We tested for positive
      selection and 2 conditions required for the evolution of MHC-based disassortative
      mating: 1) greater MHC diversity between breeding pairs compared to random
      mating, and 2) associations between MHC genotype and fitness. Cloning and
      sequencing of the DRbeta1 gene showed that Magellanic penguins had higher levels
      of genetic variation than Galapagos and Humboldt penguins. Sequence analysis
      revealed 45 alleles with 3.6% average proportion of nucleotide differences,
      nucleotide diversity of 0.030, and observed heterozygosity of 0.770. A gene
      phylogeny showed 9 allelic lineages with interspersed DRbeta1 sequences from
      Humboldt and Galapagos penguins, indicating ancestral polymorphisms. d  (N)/d 
      (S) ratios revealed evidence for positive selection. Analysis of breeding pairs
      showed no disassortative mating preferences. Significant MHC genotype/fitness
      associations in females suggest, however, that selection for pathogen resistance
      plays a more important role than mate choice in maintaining diversity at the MHC
      in the Magellanic penguin. The differential effect of MHC heterozygosity on
      fitness between the sexes is likely associated with the relative role of hatching
      and fledging rates as reliable indicators of overall fitness in males and
      females.

PMID- 22952273
TI  - Takotsubo cardiomyopathy during elective general anaesthetic induction.

PMID- 22952274
TI  - Diagnostic dilemma in CNS Behcet's disease.
AB  - A 23-year-old gentleman presented to the emergency department with new onset
      neurological dysfunction and painful oral and genital ulcers. Biopsies of the
      lesions noted non-specific inflammatory changes. MRI of the brain revealed a
      large mass-like lesion involving the pons, medulla, midbrain and surrounding
      cerebral tissue with T2 signal enhancement that was not amenable for biopsy. Both
      the ulcer biopsy results and the MRI findings could be attributed to either
      central nervous system (CNS) lymphoma or CNS Behcet's disease. A diagnosis of CNS
      Behcet's disease was thought to be most likely based on the clinical presentation
      and MRI findings. He was treated with high-dose immunosuppression and made a
      significant recovery.

PMID- 22952275
TI  - Dramatic response to inhaled dobesilate in a patient with lung squamous cell
      cancer.
AB  - The effectiveness of local application, by inhalation, of dobesilate, an
      inhibitor of fibroblast growth factor signalling, in a patient with squamous cell
      lung carcinoma is reported. To our knowledge, these are the first published data
      on the efficacy of dobesilate in the treatment of this disease. The antimitotic,
      antiangiogenic, proapoptotic and anti-inflammatory activities of dobesilate can
      be important factors to consider, in explaining the efficacy of the treatment.
      Dobesilate administration can be a therapeutic option in patients with lung
      cancer having poor performance status or severe complications.

PMID- 22952276
TI  - External auditory canal osteoma.

PMID- 22952277
TI  - The opponent matters: elevated FMRI reward responses to winning against a human
      versus a computer opponent during interactive video game playing.
AB  - Winning against an opponent in a competitive video game can be expected to be
      more rewarding than losing, especially when the opponent is a fellow human player
      rather than a computer. We show that winning versus losing in a first-person
      video game activates the brain's reward circuit and the ventromedial prefrontal
      cortex (vmPFC) differently depending on the type of the opponent. Participants
      played a competitive tank shooter game against alleged human and computer
      opponents while their brain activity was measured with functional magnetic
      resonance imaging. Brain responses to wins and losses were contrasted by fitting
      an event-related model to the hemodynamic data. Stronger activation to winning
      was observed in ventral and dorsal striatum as well as in vmPFC. Activation in
      ventral striatum was associated with participants' self-ratings of pleasure.
      During winning, ventral striatum showed stronger functional coupling with right
      insula, and weaker coupling with dorsal striatum, sensorimotor pre- and
      postcentral gyri, and visual association cortices. The vmPFC and dorsal striatum
      responses were stronger to winning when the subject was playing against a human
      rather than a computer. These results highlight the importance of social context
      in the neural encoding of reward value. 

PMID- 22952278
TI  - Metabolic maturation of the human brain from birth through adolescence: insights
      from in vivo magnetic resonance spectroscopy.
AB  - Between birth and late adolescence, the human brain undergoes exponential
      maturational changes. Using in vivo magnetic resonance spectroscopy, we
      determined the developmental profile for 6 metabolites in 5 distinct brain
      regions based on spectra from 309 children from 0 to 18 years of age. The
      concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and
      axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter)
      increased rapidly between birth and 3 months, a period of rapid axonal growth and
      synapse formation. Myo-inositol, implicated in cell signaling and a precursor of
      membrane phospholipid, as well as an osmolyte and astrocyte marker, declined
      rapidly during this period. Choline, a membrane metabolite and indicator for de
      novo myelin and cell membrane synthesis, peaked from birth until approximately 3
      months, and then declined gradually, reaching a plateau at early childhood.
      Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and
      osmoregulation, was high until approximately 3 months and thereafter declined.
      These data indicate that the first 3 months of postnatal life are a critical
      period of rapid metabolic changes in the development of the human brain. This
      study of the developmental profiles of the major brain metabolites provides
      essential baseline information for future analyses of the pediatric health and
      disease. 

PMID- 22952280
TI  - Mechanisms underlying the inhibitory effects of uroguanylin on NHE3 transport
      activity in renal proximal tubule.
AB  - We previously demonstrated that uroguanylin (UGN) significantly inhibits
      Na(+)/H(+) exchanger (NHE)3-mediated bicarbonate reabsorption. In the present
      study, we aimed to elucidate the molecular mechanisms underlying the action of
      UGN on NHE3 in rat renal proximal tubules and in a proximal tubule cell line (LLC
      PK(1)). The in vivo studies were performed by the stationary microperfusion
      technique, in which we measured H(+) secretion in rat renal proximal segments,
      through a H(+)-sensitive microelectrode. UGN (1 MUM) significantly inhibited the
      net of proximal bicarbonate reabsorption. The inhibitory effect of UGN was
      completely abolished by either the protein kinase G (PKG) inhibitor KT5823 or by
      the protein kinase A (PKA) inhibitor H-89. The effects of UGN in vitro were found
      to be similar to those obtained by microperfusion. Indeed, we observed that
      incubation of LLC-PK(1) cells with UGN induced an increase in the intracellular
      levels of cAMP and cGMP, as well as activation of both PKA and PKG. Furthermore,
      we found that UGN can increase the levels of NHE3 phosphorylation at the PKA
      consensus sites 552 and 605 in LLC-PK(1) cells. Finally, treatment of LLC-PK(1)
      cells with UGN reduced the amount of NHE3 at the cell surface. Overall, our data
      suggest that the inhibitory effect of UGN on NHE3 transport activity in proximal
      tubule is mediated by activation of both cGMP/PKG and cAMP/PKA signaling pathways
      which in turn leads to NHE3 phosphorylation and reduced NHE3 surface expression.
      Moreover, this study sheds light on mechanisms by which guanylin peptides are
      intricately involved in the maintenance of salt and water homeostasis.

PMID- 22952279
TI  - Calmodulin-sensitive adenylyl cyclases mediate AVP-dependent cAMP production and
      Cl- secretion by human autosomal dominant polycystic kidney cells.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), binding of AVP to the V2
      receptor (V2R) increases cAMP and accelerates cyst growth by stimulating cell
      proliferation and Cl(-)-dependent fluid secretion. Basal cAMP is elevated in
      human ADPKD cells compared with normal human kidney (NHK) cells. V2R mRNA levels
      are elevated in ADPKD cells; however, AVP caused a greater increase in global
      cAMP in NHK cells, suggesting an intrinsic difference in cAMP regulation.
      Expression, regulatory properties, and receptor coupling of specific adenylyl
      cyclases (ACs) provide temporal and spatial regulation of the cAMP signal. ADPKD
      and NHK cells express mRNAs for all nine ACs. Ca(2+)-inhibited ACs 5 and 6 are
      increased in ADPKD cells, while Ca(2+)/CaM-stimulated ACs 1 and 3 are
      downregulated. ACs 1, 3, 5, and 6 were detected in cyst cells in situ, and
      codistribution with aquaporin-2 suggests that these cysts were derived from
      collecting ducts. To determine the contribution of CaM-sensitive ACs to AVP
      signaling, cells were treated with W-7, a CaM inhibitor. W-7 decreased AVP
      induced cAMP production and Cl(-) secretion by ADPKD cells. CaMKII inhibition
      increased AVP-induced cAMP, suggesting that cAMP synthesis is mediated by AC3. In
      contrast, CaM and CaMKII inhibition in NHK cells did not affect AVP-induced cAMP
      production. Restriction of intracellular Ca(2+) switched the response in NHK
      cells, such that CaM inhibition decreased AVP-induced cAMP production. We suggest
      that a compensatory response to decreased Ca(2+) in ADPKD cells switches V2R
      coupling from Ca(2+)-inhibited ACs 5/6 to Ca(2+)/CaM-stimulated AC3, to mitigate
      high cAMP levels in response to continuous AVP stimulation.

PMID- 22952281
TI  - Regulation of glomerulotubular balance: II: impact of angiotensin II on flow
      dependent transport.
AB  - Underlying glomerulotubular balance (GTB) is the impact of axial flow to regulate
      Na(+) and HCO(3)(-) transport by modulating Na(+)-H(+) exchanger 3 (NHE3) and H
      ATPase activity. It is not known whether the cascade of events following a change
      in flow relies on local angiotensin (ANG II) generation or receptor availability.
      Mouse tubules were microperfused in vitro at flows of 5 and 20 nl/min, and net
      fluid (J(v)) and HCO(3)(-) (J(HCO3)) absorption and cell height were measured.
      Na(+) (J(Na)) and Cl(-) (J(Cl)) absorption and changes in microvillous torque
      were estimated. Raising flow increased Na(+) and HCO(3)(-) reabsorption but did
      not change either Cl(-) transport or cell volume. Losartan reduced absolute Na(+)
      and HCO(3)(-) absorption at both low and high flows but did not affect fractional
      flow-stimulated transport. Compared with controls, in AT(1a) knockout (KO) mouse
      tubules, 53% of flow-stimulated Na(+) absorption was abolished, but flow
      stimulated HCO(3)(-) absorption was retained at similar levels. The remaining
      flow-stimulated J(HCO3) was eliminated by the H-ATPase inhibitor bafilomycin.
      Inhibition of the AT(2) receptor by PD123319 increased both J(Na) and J(HCO3) but
      did not affect flow-mediated fractional changes. NHE3 expression at the protein
      level was reduced in AT(1a) KO mice kidneys. We conclude that 1) although the
      AT(1a) receptor is necessary for flow to impact NHE3, the effect on H(+)-ATPase
      is independent of AT(1a); 2) the small flow-mediated changes in cell volume
      suggest a coordinate flow effect on both luminal and basolateral transporters;
      and 3) there is no evidence of flow-dependent Cl(-) transport, and thus no
      evidence for convective paracellular Cl(-) transport in mouse tubules.

PMID- 22952283
TI  - Connexin 40 mediates tubuloglomerular feedback paracrine signaling by coupling
      tubular and vascular cells in the renal juxtaglomerular apparatus.

PMID- 22952282
TI  - Intrarenal localization of the plasma membrane ATP channel pannexin1.
AB  - In the renal tubules, ATP released from epithelial cells stimulates purinergic
      receptors, regulating salt and water reabsorption. However, the mechanisms by
      which ATP is released into the tubular lumen are multifaceted. Pannexin1 (Panx1)
      is a newly identified. ubiquitously expressed protein that forms connexin-like
      channels in the plasma membrane, which have been demonstrated to function as a
      mechanosensitive ATP conduit. Here, we report on the localization of Panx1 in the
      mouse kidney. Using immunofluorescence, strong Panx1 expression was observed in
      renal tubules, including proximal tubules, thin descending limbs, and collecting
      ducts, along their apical cell membranes. In the renal vasculature, Panx1
      expression was localized to vascular smooth muscle cells in renal arteries,
      including the afferent and efferent arterioles. Additionally, we tested whether
      Panx1 channels expressed in renal epithelial cells facilitate luminal ATP release
      by measuring the ATP content of urine samples freshly collected from wild-type
      and Panx1(-/-) mice. Urinary ATP levels were reduced by 30% in Panx1(-/-)
      compared with wild-type mice. These results suggest that Panx1 channels in the
      kidney may regulate ATP release and via purinergic signaling may participate in
      the control of renal epithelial fluid and electrolyte transport and vascular
      functions.

PMID- 22952284
TI  - Mesenchymal stem cell therapy promotes renal repair by limiting glomerular
      podocyte and progenitor cell dysfunction in adriamycin-induced nephropathy.
AB  - We previously reported that in a model of spontaneously progressive glomerular
      injury with early podocyte loss, abnormal migration, and proliferation of
      glomerular parietal epithelial progenitor cells contributed to the formation of
      synechiae and crescentic lesions. Here we first investigated whether a similar
      sequence of events could be extended to rats with adriamycin (ADR)-induced
      nephropathy. As a second aim, the regenerative potential of therapy with bone
      marrow-derived mesenchymal stem cells (MSCs) on glomerular resident cells was
      evaluated. In ADR-treated rats, decrease of WT1(+) podocyte number due to
      apoptosis was associated with reduced glomerular expression of nephrin and CD2AP.
      As a consequence of podocyte injury, glomerular adhesions of the capillary tuft
      to the Bowman's capsule were observed, followed by crescent-like lesions and
      glomerulosclerosis. Cellular components of synechiae were either NCAM(+) parietal
      progenitor cells or nestin(+) podocytes. In ADR rats, repeated injections of MSCs
      limited podocyte loss and apoptosis and partially preserved nephrin and CD2AP.
      MSCs attenuated the formation of glomerular podocyte-parietal epithelial cell
      bridges and normalized the distribution of NCAM(+) progenitor cells along the
      Bowman's capsule, thereby reducing glomerulosclerosis. Finding that MSCs
      increased glomerular VEGF expression and limited microvascular rarefaction may
      explain the prosurvival effect by stem cell therapy. MSCs also displayed anti
      inflammatory activity. Coculture of MSCs with ADR-damaged podocytes showed a
      functional role of stem cell-derived VEGF on prosurvival pathways. These data
      suggest that MSCs by virtue of their tropism for damaged kidney and ability to
      provide a local prosurvival environment may represent a useful strategy to
      preserve podocyte viability and reduce glomerular inflammation and sclerosis.

PMID- 22952285
TI  - T-wave inversion on electrocardiogram is related to the risk of acute coronary
      syndrome in the general population.
AB  - BACKGROUND: T-wave inversion (TWI) is a frequently encountered
      electrocardiographic (ECG) finding during routine medical examination of
      asymptomatic individuals, and of patients with various clinical conditions.
      However, the role of isolated TWI in the prediction of acute coronary syndrome
      (ACS) in the community has not been extensively studied. We investigated the
      relationship between TWI in routine ECG and the risk for ACS in the general
      population. METHODS: This study is based on a random sample of 1997 men aged 42
      60 years in Eastern Finland. Electrocardiograms recorded at rest were classified
      using the Minnesota codes. The association between isolated TWI and ACS was
      determined using a multivariable adjusted Cox proportional hazard model. RESULTS:
      Negative T-waves were present in 3.6% of the participants. During an average
      follow-up of 20 years, a total of 493 ACS events were registered. After adjusting
      for age, TWI was associated with a 3.10-fold (95% confidence interval (CI) 2.21
      4.32) risk for ACS. After additional adjustment for previously known coronary
      risk factors, TWI remained statistically significant in predicting ACS (relative
      risk 2.23; 95% CI 1.57-3.15). Negative T-waves was one of the strongest risk
      markers for ACS compared with other ECG-based variables such as left ventricular
      hypertrophy, previous Q-wave and prolonged QRS duration. CONCLUSION: TWI has a
      strong and independent predictive value for ACS in the general population.

PMID- 22952286
TI  - Chronic aspirin and statin therapy in patients with impaired renal function and
      acute coronary syndromes: results from the IN-ACS Outcome Registry.
AB  - BACKGROUND: The cardioprotective role that statin and aspirin has appears to be
      reduced in patients with chronic kidney disease (CKD). This analysis aims to
      evaluate the impact of statin and aspirin on the outcome of patients with CKD and
      acute coronary syndrome (ACS). METHODS: All patients who were enrolled in the IN
      ACS Outcome registry, diagnosed with CKD, were included in our analysis. We
      divided patients into four groups, according to previous chronic therapy: neither
      aspirin nor statin therapy (Group 1), aspirin only therapy (Group 2), statin only
      therapy (Group 3) and aspirin plus statin therapy (Group 4). RESULTS: Of the 5483
      patients enrolled that had data on glomerular filtration rate available, 1484 had
      CKD: These segregated into 589 patients in Group 1, 477 in Group 2, 89 in Group 3
      and 329 in Group 4. Despite having a higher baseline risk profile, groups 3 and
      4, as compared to the other two groups, exhibited a significantly lower in
      hospital mortality (1% in Group 3, 2% in Group 4; but 8% in Group 1 and 7% in
      Group 2, p = 0.0007); while at 30 days it remained so, as it was 1% in Group 3,
      4% in Group 4 (and 10% in Group 1 and 10% in Group 2 p = 0.0002); and at 1 year
      it was 11% in Group 3 and 13% in Group 4 (compared to 20% in Group 1 and 23% in
      Group 2, p = 0.0012). CONCLUSIONS: In a large cohort of patients with CKD and
      ACS, chronic treatment with statin or the combination of aspirin and statin is
      associated with short-term and long-term better outcomes for in-hospital
      mortality, as compared to those receiving no therapy or aspirin therapy alone.

PMID- 22952287
TI  - Insulin resistance status and four-year changes in other cardiometabolic risk
      factors in West-African adults: the Benin study.
AB  - BACKGROUND: The association of insulin resistance (IR) with other cardiometabolic
      risk (CMR) factors in sub-Saharan Africans is poorly documented. This study
      examined the links between IR and the evolution of blood pressure (BP),
      glycaemia, serum lipids and abdominal obesity in the population of Benin. DESIGN:
      Population-based longitudinal study. METHODS: This study initially included 541
      apparently healthy Beninese adults (50% women) aged 25-60 years who were randomly
      selected in a large city, a small town and a rural area. After a baseline survey,
      our subjects were followed up after 2 years, and again at 4 years. IR based on
      homeostasis model assessment (HOMA), blood glucose, BP, waist circumference (WC),
      triglycerides, total cholesterol and HDL-cholesterol were measured. Complete data
      at the end of the follow-up periods was available for 416 subjects. RESULTS: IR
      was more prevalent in women than in men (33.2% versus 17.8%) and it was generally
      associated with more adverse values of CMR factors, excepting BP. In controlling
      for baseline age, sex, WC, diet, lifestyle variables and WC changes; the relative
      risk (RR) of hyperglycemia over 4 years was as least 3-fold in IR subjects,
      compared to normal subjects. The RR of abdominal obesity was 5.3 (1.04-26.93) in
      IR women, compared to non-IR. The association of IR with the evolution of
      dyslipidemia was inconsistent, but IR tended to exacerbate low HDL-cholesterol.
      CONCLUSION: Over 4 years, IR exacerbated hyperglycemia in both men and women, and
      abdominal obesity in women, but IR did not affect blood pressure. Further
      research on the link found between IR and dyslipidemia, particularly low HDL-C,
      is needed in sub-Saharan Africa.

PMID- 22952288
TI  - Gender difference in long-term prognosis among patients with cardiovascular
      disease.
AB  - BACKGROUND: Differences in prognosis between women and men with atherosclerosis
      are currently under attention. Previous studies describe contradictory results
      and are restricted to one cardiovascular bed, while atherosclerosis is a systemic
      disease. We therefore studied the prognosis of women versus men in the SMART
      study, a large cohort of patients with clinically manifest atherosclerosis with
      extensive baseline and follow-up information. METHODS: 5349 patients (1347 women,
      4002 men) with at least one type of atherosclerotic vascular disease (coronary
      artery disease, cerebrovascular disease, peripheral arterial disease or abdominal
      aortic aneurysm) were included in the SMART study, an ongoing long-term follow-up
      study. They all received a standardized cardiovascular work-up with a
      personalized therapy advice. All future cardiovascular events were collected
      prospectively. All-cause mortality, cardiovascular mortality and cardiovascular
      outcome (composite of myocardial infarction, stroke and cardiovascular death)
      were evaluated using Cox regression and expressed as hazard ratios (HR) with 95%
      confidence intervals (95%CI). Men served as the reference category. Different
      models were used to adjust for differences in baseline characteristics. RESULTS:
      Women and men had a mean age of 60 years and their median follow-up (range) was
      five years (13.5). The hazard ratios of all-cause mortality, cardiovascular death
      and cardiovascular outcome were 0.62 (95%CI: 0.51-0.75), 0.59 (95%CI: 0.46-0.75)
      and 0.73 (95%CI: 0.60-0.87). Neither differences in risk-factor profile nor the
      different vascular beds involved could explain this advantage. CONCLUSION: Women
      with cardiovascular disease who received a similar standardized cardiovascular
      work-up and personalized therapy advice as men had a favourable long-term
      outcome.

PMID- 22952289
TI  - Smoking cessation interventions following acute coronary syndrome: a missed
      opportunity?
AB  - BACKGROUND: It is recommended that general practitioners (GPs) offer cessation
      advice and pharmacological interventions to smokers with acute coronary syndrome
      (ACS). The study objective was to describe the extent to which this is done, and
      to describe outcomes by smoking status. DESIGN: Patients aged 30+ hospitalised
      for troponin-positive ACS from 2002 to 2009, discharged home alive, were
      identified in the Myocardial Ischaemia National Audit Project registry. Patient
      data were linked to the General Practice Research Database, Hospital Episode
      Statistics, and Office of National Statistics mortality data, enabling a unique
      perspective of longitudinal smoking data. Patients who smoked prior to the
      hospitalisation had GP interventions and quitting status established in the 3
      months following discharge, and were followed up for major clinical outcomes.
      METHODS: The outcomes evaluated included death, repeat ACS, stroke, heart
      failure, and major adverse cardiac events (MACE). RESULTS: Of the 4834 patients
      included, 965 (20%) were smokers at the time of their ACS. After the ACS event,
      only 225 (24%) received any GP smoking intervention within 3 months, with 82 (9%)
      receiving advice only, and 143 (15%) receiving a pharmacological intervention.
      Patients who quit (320; 33%) were at a decreased risk of mortality (relative risk
      (RR) 0.49; 95% confidence interval (CI) 0.35-0.69) and MACE (RR 0.61; 0.46-0.80)
      compared with patients who did not. CONCLUSIONS: Whilst a high proportion of
      patients with ACS are smokers, there is a low level of GP cessation intervention
      following hospital discharge. This missed opportunity of patient care is
      important given the decreased risk of mortality and MACE found amongst those who
      quit.

PMID- 22952290
TI  - The dysfunction of ammonia in heart failure increases with an increase in the
      intensity of resistance exercise, even with the use of appropriate drug therapy.
AB  - BACKGROUND: Hyperammonemia during rest periods is a dysfunction in heart failure
      (HF). The low formation of ammonia during exercise reflects an inefficiency of
      purine metabolism. Hyperkalemia in response to physical exercise is common in HF
      and may contribute to a contractile inefficiency in type II fibers, leading to
      early fatigue. We tested the hypothesis that during resistance exercise of high
      intensity and low volume, this disorder of ammonia metabolism would be more
      intense, due to the hyperkalemia present in HF. METHODS: Alternating resistance
      exercise (RE) of low intensity and high volume, and high intensity and low
      volume, were applied to 18 patients with an interval of 7 days between them
      (functional class II-III New York Heart Association, FE = 33.5 +/- 4%) and
      compared with 22 healthy controls matched for age and gender. Ammonia, potassium
      and lactate levels were assessed before and immediately after the RE. RESULTS:
      Significant differences: Deltas (control vs. HF) in 40% RE: lactate (mg/dl) 26.3
      +/- 10 vs. 37.7 +/- 7; p < 0,001, ammonia (ug/dl) 92.5 +/- 18 vs. 48.9 +/- 9; p <
      0.001. Deltas (control vs. HF) in 80%RE: lactate(mg/dl) 45.0 +/- 12 vs. 54.1 +/-
      11; p < 0.05, ammonia(ug/dl) 133.5 +/- 22 vs. 32.2 +/- 7; p < 0.001, potassium
      (mEq/L) 1.6 +/- 0.4 vs. 2.0 +/- 0.8; p < 0.05. A negative correlation was found
      between the deltas of ammonia and potassium (r = -0.74, p < 0.001) in the HF
      group. CONCLUSIONS: We conclude that in HF, there is an inefficiency of purine
      metabolism that increases with increasing exercise intensity, but not with an
      increase of total volume. These findings suggest that hyperkalemia may play an
      important role in the disorders of purine metabolism.

PMID- 22952291
TI  - Dyslipidaemia in patients with established cardiovascular disease in Sub-Saharan
      Africa: a systematic review and meta-analysis.
AB  - Dyslipidaemia has been recognized as a major risk factor for cardiovascular
      diseases. Our objectives were to conduct a systematic review and meta-analysis of
      published studies to determine the prevalence of dyslipidaemia among hospitalized
      adult patients with cardiovascular disease in sub-Saharan Africa and to compare
      between the various cardiovascular disease types. We searched Internet-based
      search tools and other sources for studies on dyslipidaemia or
      hypercholesterolaemia among hospitalized adult patients with established
      cardiovascular disease in sub-Saharan Africa, from 1985 to May 2011. Established
      cardiovascular disease was defined as ischaemic heart disease, heart failure,
      stroke or chronic kidney disease. We then assessed for between-study
      heterogeneity and carried out sensitivity analyses. Study quality was assessed
      using Downs and Black Checklist and publication bias was considered present when
      positive in both Egger's and Begg's tests. Restricted analyses were then
      performed on data from studies on ischaemic heart disease, heart failure and
      stroke separately. A total of 451 studies were screened and eventually 16 studies
      were included with a total of 2584 persons. The overall estimate of dyslipidaemia
      was 38.38% (95% confidence intervals = 26.75-50.0; I(2 )= 96.878; p < 0.001). The
      prevalence was highest among those with ischaemic heart disease (49.64%) than
      among those with stroke (26.53%) or heart failure (15.4%; p-values for all
      comparisons<0.001). Prevalence of dyslipidaemia in subjects with cardiovascular
      disease including ischaemic heart disease, stroke and heart failure in sub
      Saharan Africa was high and similar to what was obtained in Western Europe and
      North America; highest in subjects with ischaemic heart disease, followed by
      those with stroke and heart failure. 

PMID- 22952293
TI  - Watchful waiting versus intravesical BCG therapy for high-grade pT1 bladder
      cancer with pT0 histology after second transurethral resection: Japan Clinical
      Oncology Group Study JCOG1019.
AB  - A Phase III clinical trial has been started in Japan to determine the optimal
      treatment strategy for patients with high-grade pT1 bladder cancer who have pT0
      histology after second transurethral resection. The aim of this trial is to
      demonstrate the non-inferiority of relapse-free survival (excluding Tis or Ta
      intravesical recurrence) for watchful waiting compared with intravesical bacillus
      Calmette-Guerin therapy for pT0 after second transurethral resection. Patients
      with high-grade pT1 bladder cancer at the first registration and pT0 after second
      transurethral resection at the second registration are randomized to either a
      watchful waiting arm or an intravesical bacillus Calmette-Guerin therapy arm. A
      total of 575 patients at the first registration and 260 patients at the second
      registration will be accrued for this study from 38 institutions over 5 years.
      The primary endpoint is relapse-free survival (excluding Tis or Ta intravesical
      recurrence), and the secondary endpoints are overall survival, metastasis-free
      survival with bladder preserved, annual proportion of intravesical relapse-free
      survival, annual proportion of T2 or deeper relapse-free survival, adverse events
      and serious adverse events.

PMID- 22952292
TI  - Association of isolated minor non-specific ST-segment and T-wave abnormalities
      with subclinical atherosclerosis in a middle-aged, biracial population: Coronary
      Artery Risk Development in Young Adults (CARDIA) study.
AB  - AIMS: Isolated minor non-specific ST-segment and T-wave abnormalities (NSSTTAs)
      are common and known to be independent electrocardiographic risk markers for
      future cardiovascular disease (CVD) events. The association of NSSTTA with
      subclinical atherosclerosis is not well defined, but has been postulated as a
      potential mechanism of association with future clinical events. METHODS AND
      RESULTS: We studied participants from the Year 20 examination of the middle-aged,
      biracial CARDIA cohort. This examination included measurement of traditional risk
      factors, 12-lead electrocardiograms (ECGs), coronary artery calcium (CAC)
      measurement and common carotid intima-media thickness (CC-IMT). ECGs were coded
      using both Minnesota Code (MC) and Novacode (NC) criteria. Isolated minor STTA
      was defined by MC as presence of MC 4-3, 4-4, 5-3, or 5-4, and by NC as presence
      of NC 5.8. ECGs with secondary causes of STTA (i.e., LVH) were excluded.
      Multivariable logistic regression was used to determine the cross-sectional
      association of isolated minor NSSTTAs with CAC and CC-IMT. The study sample
      consisted of 2175 participants with an average age of 45 years (57% female and
      43% Black). Isolated NSSTTAs were present in 5.1% of males and 6.3% of females.
      No association was observed between NSSTTA and CAC. After multivariable
      adjustment for traditional CVD risk factors, the presence of isolated minor
      NSSTTAs remained significantly associated with the extent of CC-IMT (odds ratio
      1.25 (1.06-1.48), p < 0.01). This association remained significant after further
      adjustment for CAC. CONCLUSIONS: Isolated minor NSSTTAs were associated with the
      extent of CC-IMT, but not with CAC, in this middle-aged biracial cohort. Further
      study is needed to elucidate potential mechanisms for these findings.

PMID- 22952294
TI  - Short-term administration of diclofenac sodium affects renal function after
      laparoscopic radical nephrectomy in elderly patients.
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drugs decrease the glomerular
      filtration rate. However, few studies have been conducted on renal function in
      patients treated with non-steroidal anti-inflammatory drugs during the first week
      after laparoscopic radical nephrectomy. The purpose of this study is to determine
      whether short-term administration of non-steroidal anti-inflammatory drugs during
      the first week after laparoscopic radical nephrectomy is a risk factor for
      impaired renal function. METHODS: Renal carcinoma patients undergoing
      laparoscopic radical nephrectomy in Nagoya University Hospital from April 2004 to
      July 2010 were identified in a retrospective cohort study. The 164 patients were
      divided into non-non-steroidal anti-inflammatory drug-treated (n=50) and non
      steroidal anti-inflammatory drug-treated (n=114) groups. RESULTS: Elderly
      patients (>60 years old) in the non-steroidal anti-inflammatory drug-treated
      group showed a significant correlation between the residual renal function ratio
      and the total dose of diclofenac sodium (r=-0.277, P<0.05). There was no
      significant correlation between the residual renal function ratio and the total
      dose of loxoprofen sodium. The time to doubling of the serum creatinine level was
      significantly shorter in elderly patients treated with diclofenac sodium compared
      with that in patients treated with non-non-steroidal anti-inflammatory drugs
      (P=0.034). These results suggest that renal ischemia induced by short-term
      administration of diclofenac sodium impairs renal function in elderly patients
      after laparoscopic radical nephrectomy. CONCLUSIONS: In the present study, we
      found the first evidence that short-term administration of diclofenac sodium is
      one risk factor for renal impairment after laparoscopic radical nephrectomy in
      elderly patients. To prevent renal impairment after laparoscopic radical
      nephrectomy in elderly patients, the use of loxoprofen sodium, which has a
      negligible effect on renal function compared with diclofenac sodium, is
      recommended.

PMID- 22952295
TI  - Trends in 'cure' fraction from colorectal cancer by age and tumour stage between
      1975 and 2000, using population-based data, Osaka, Japan.
AB  - Since the 1960s, Japan has experienced a striking increase in the incidence of
      colorectal cancer, now the second most common cancer in the country. Meanwhile,
      the management of colorectal cancer has changed dramatically with the
      implementation of, for example, screening, endoscopy and adjuvant chemotherapy.
      It is therefore of interest to monitor the long-term trends in population 'cure'
      in Japan. We analysed 33 885 colorectal cancer cases diagnosed between 1975 and
      2000 in Osaka. We applied the multivariable mixture cure model to estimate cure
      fraction and median survival time (MST) for 'uncured' patients, by sex, age,
      stage, period at diagnosis and subsite. For colon cancer, the cure fraction
      increased by about 25%, while MST for the uncured was prolonged from 8 to 12
      months. The cure fraction was 5% higher in men than in women, while MST was
      similar in both. The cure fraction also increased for localized and regional
      tumours. For rectal cancer, the cure fraction increased by about 25-30%, but
      remained lower than for colon cancer. From the late 1970s, the cure fraction for
      colorectal cancer increased dramatically due to better management of detection
      and care for colorectal cancer. This improvement was obtained at the cost of
      shorter MST for uncured patients.

PMID- 22952296
TI  - The lack of CD34 expression in gastrointestinal stromal tumors is related to
      cystic degeneration following imatinib use.
AB  - OBJECTIVE: We evaluated the characteristics of the gastrointestinal stromal
      tumors that showed discrepancies between their assessment using the Response
      Evaluation Criteria in Solid Tumor (RECIST) and Choi's criteria. We also
      investigated the clinical applicability of Choi's criteria to Korean
      gastrointestinal stromal tumor patients undergoing imatinib therapy. METHODS:
      Patients with advanced gastrointestinal stromal tumors treated with frontline
      imatinib were analyzed. Computed tomography images of these patients were
      reviewed and genotyping for the KIT and PDGFRA genes was performed.
      Immunohistochemical staining of c-KIT, CD34, platelet derived growth factor
      receptor-alpha, platelet derived growth factor receptor-beta, AKT, P-ERK and
      vascular endothelial growth factor was followed. RESULTS: Ninety-five patients
      were enrolled. When using Choi's criteria to evaluate the 61 patients who
      achieved at least partial response by Choi's criteria, 27 patients showed
      discrepancies in their response to treatment between these two sets of criteria.
      A lack of CD34 expression in tumors was found to be related to cystic
      degeneration after imatinib treatment (P=0.001). Patients who showed partial
      response by Choi's criteria but stable disease by RECIST criteria had a similar
      progression-free survival to cases who showed a partial response under both
      systems (P=0.951). CONCLUSIONS: Gastrointestinal stromal tumors showing cystic
      degeneration after imatinib treatment lack CD34 expression. Choi's criteria have
      a clinical value in terms of the progression-free survival in Korean patients
      treated with imatinib.

PMID- 22952297
TI  - Maternal smoking in pregnancy and asthma in preschool children: a pooled analysis
      of eight birth cohorts.
AB  - RATIONALE: Although epidemiological studies suggest that exposure to maternal
      smoking during fetal and early life increases the risk of childhood wheezing and
      asthma, previous studies were not able to differentiate the effects of prenatal
      from postnatal exposure. OBJECTIVES: To assess the effect of exposure to maternal
      smoking only during pregnancy on wheeze and asthma among preschool-age children.
      METHODS: A pooled analysis was performed based on individual participant data
      from eight European birth cohorts. Cohort-specific effects of maternal smoking
      during pregnancy, but not during the first year, on wheeze and asthma at 4 to 6
      years of age were estimated using logistic regression and then combined using a
      random effects model. Adjustments were made for sex, parental education, parental
      asthma, birth weight, and siblings. MEASUREMENTS AND MAIN RESULTS: Among the
      21,600 children included in the analysis, 735 children (3.4%) were exposed to
      maternal smoking exclusively during pregnancy but not in the first year after
      birth. In the pooled analysis, maternal smoking only during pregnancy was
      associated with wheeze and asthma at 4 to 6 years of age, with adjusted odds
      ratios of 1.39 (95% confidence interval, 1.08-1.77) and 1.65 (95% confidence
      interval, 1.18-2.31), respectively. The likelihood to develop wheeze and asthma
      increased statistically significantly in a linear dose-dependent manner in
      relation to maternal daily cigarette consumption during the first trimester of
      pregnancy. CONCLUSIONS: Maternal smoking during pregnancy appears to increase the
      risk of wheeze and asthma among children who are not exposed to maternal smoking
      after birth.

PMID- 22952298
TI  - Characterization and turnover of CD73/IP(3)R3-positive microvillar cells in the
      adult mouse olfactory epithelium.
AB  - The main olfactory epithelium consists of 4 major cell types: sensory neurons,
      supporting cells, microvillar cells, and basal progenitor cells. Several
      populations of microvillar olfactory cells have been described, whose properties
      are not yet fully understood. In this study, we aimed to clarify the
      classification of microvillar cells by introducing a specific marker, CD73.
      Furthermore, we investigated the turnover of CD73-microvillar cells during adult
      life. Using direct and indirect immunofluorescence in adult main olfactory
      epithelium, we first demonstrate that ecto-5'-nucleotidase (CD73) is a reliable
      marker for microvillar cells reported previously to express phospholipase C beta2
      (PLC beta2) along with type 3 IP(3) receptors (IP(3)R3) and transient receptor
      potential channels 6 (TRPC6), as well as for cells labeled by transgenic
      expression of tauGFP driven by the IP(3)R3 promoter. The ubiquitous CD73
      immunoreactivity in the microvilli of these 2 cell populations indicates that
      they correspond to the same cell type (CD73-microvillar cell), endowed with a
      signal transduction cascade mobilizing Ca(++) from intracellular stores. These
      microvillar cells respond to odors, possess a basal process, and do not
      degenerate after bulbectomy, suggesting that they contribute to cellular
      homeostasis in the olfactory epithelium. Next, we examined whether CD73
      microvillar cells undergo turnover in the adult olfactory epithelium. By
      combining CD73 immunofluorescence and BrdU pulse labeling, we show delayed BrdU
      incorporation in a small fraction of CD73-positive microvillar cells, which
      persists for several weeks after BrdU administration. These findings indicate
      that CD73-microvillar cells likely differentiate from proliferating progenitor
      cells and have a slow turnover despite their apical position in the olfactory
      epithelium. These combined properties are unique among olfactory cells, in line
      with the possibility that they might regulate cellular homeostasis driven by
      extracellular ATP and adenosine.

PMID- 22952299
TI  - Functional reconstitution of olfactory receptor complex on baculovirus.
AB  - Despite that recent progress in genomics has elucidated the genomic structure of
      the olfactory receptors (ORs), most of them are still orphan receptors. The low
      expression level of ORs in heterologous cells has hampered many attempts to
      establish cell biological OR assay systems. Recently, we demonstrated that
      certain G protein-coupled receptors, such as the leukotriene B4 receptor or the
      dopamine D1 receptor, were efficiently reconstituted on baculovirus budding from
      infected Sf9 cells. The budded virus (BV) was shown to be mostly free of
      exogenous proteins other than those related to viral infection, resulting in low
      noise assay conditions. Taking advantage of these conditions, we attempted to
      reconstitute OR complexes on BV. Sf9 cells were coinfected with recombinant
      baculoviruses harboring the cDNAs encoding adenylyl cyclase, trimeric G-protein,
      and the receptor: mOR-EG or S6. The coexpression of these proteins was detected
      by western blot, and the agonist- or antagonist-dependent receptor response was
      confirmed using ligand-dependent cyclic AMP production. These results
      demonstrated the successful reconstitution of functional OR complex on BV.
      Additionally, the expression of OR8B3 on BV, one of human orphan ORs, was also
      confirmed. This BV expression system is expected to be a highly effective tool
      for screening unknown ligands for ORs.

PMID- 22952301
TI  - Improving image retrieval effectiveness via query expansion using MeSH
      hierarchical structure.
AB  - OBJECTIVE: We explored two strategies for query expansion utilizing medical
      subject headings (MeSH) ontology to improve the effectiveness of medical image
      retrieval systems. In order to achieve greater effectiveness in the expansion,
      the search text was analyzed to identify which terms were most amenable to being
      expanded. DESIGN: To perform the expansions we utilized the hierarchical
      structure by which the MeSH descriptors are organized. Two strategies for
      selecting the terms to be expanded in each query were studied. The first
      consisted of identifying the medical concepts using the unified medical language
      system metathesaurus. In the second strategy the text of the query was divided
      into n-grams, resulting in sequences corresponding to MeSH descriptors.
      MEASUREMENTS: For the evaluation of the system, we used the collection made
      available by the ImageCLEF organization in its 2011 medical image retrieval task.
      The main measure of efficiency employed for evaluating the techniques developed
      was the mean average precision (MAP). RESULTS: Both strategies exceeded the
      average MAP score in the ImageCLEF 2011 competition (0.1644). The n-gram
      expansion strategy achieved a MAP of 0.2004, which represents an improvement of
      21.89% over the average MAP score in the competition. On the other hand, the
      medical concepts expansion strategy scored 0.2172 in the MAP, representing a
      32.11% improvement. This run won the text-based medical image retrieval task in
      2011. CONCLUSIONS: Query expansion exploiting the hierarchical structure of the
      MeSH descriptors achieved a significant improvement in image retrieval systems.

PMID- 22952302
TI  - In situ observation of Pt nanoparticles on graphene layers under high temperature
      using aberration-corrected transmission electron microscopy.
AB  - To study their thermal stability, we observed Pt colloidal nanoparticles on
      terraced graphene layers at high temperatures using aberration-corrected
      transmission electron microscopy. Not only Pt nanoparticles but also single Pt
      atoms were formed on the graphene layers by heating Pt colloids to 500-800
      degrees C. High resolution in situ observation showed that Pt nanoparticles and
      single atoms anchored to the edge of the graphene layers were relatively
      stationary under elevated temperatures, although some Pt atoms migrated on the
      graphene surfaces. The results indicated that the Pt single atoms at the edge of
      the graphene exhibited high-temperature stability.

PMID- 22952303
TI  - Reducing falls among geriatric rehabilitation patients: a controlled clinical
      trial.
AB  - OBJECTIVE: To evaluate the effectiveness of an intervention programme to reduce
      falls among geriatric rehabilitation patients. DESIGN: Pre/post-test design with
      independent pre-test and matched post-test samples. SETTING: Inpatient geriatric
      wards in a rehabilitation hospital. PARTICIPANTS: Seventy-six matched pairs (n =
      152) of geriatric rehabilitation patients from one control and one intervention
      ward participated in the study, and 36 nursing staff surveys were completed.
      INTERVENTION: The intervention programme was developed based on interviews and
      systematic reviews. Educational materials were distributed to patients and
      families, and preventive measures were implemented. MAIN OUTCOME MEASURES: The
      rates of falls before and after the intervention both within and between the
      wards were compared, and surveys were completed. RESULTS: The matched patients
      presented no significant differences on age, gender or medical conditions. The
      falls rates, proportion of fallers and length of stay was higher among those in
      the control ward (P< 0.043). The percentage of fallers and the rate of falls/1000
      patient days were lower on the intervention ward after implementation: odds ratio
      (95% confidence interval) = -2.9 (-6.6, -1.2) and -1.8 (-6.0, 0.5). Thirty of 36
      respondents considered the tool to be helpful and beneficial for use on other
      wards. CONCLUSION: The intervention programme was effective in reducing falls
      among geriatric rehabilitation patients.

PMID- 22952304
TI  - Effect of therapist-based constraint-induced therapy at home on motor control,
      motor performance and daily function in children with cerebral palsy: a
      randomized controlled study.
AB  - OBJECTIVE: To determine the effect of therapist-based constraint-induced therapy
      at home on motor performance, daily function and reaching control for children
      with cerebral palsy. DESIGN: A single-blinded, randomized controlled trial.
      SUBJECTS: Forty-seven children (23 boys; 24 girls) with unilateral cerebral
      palsy, aged 6-12 years, were randomized to constraint-induced therapy (n = 24) or
      traditional rehabilitation (n = 23). INTERVENTIONS: Constraint-induced therapy
      involved intensive functional training of the more affected arm while the less
      affected arm was restrained. Traditional rehabilitation involved functional
      unilateral and bilateral arm training. Both groups received individualized
      therapist-based interventions at home for 3.5-4 hours/day, two days a week for
      four weeks. MAIN MEASURES: Motor performance and daily function were measured by
      the Peabody Developmental Motor Scale, Second Edition and the Pediatric Motor
      Activity Log. Reaching control was assessed by the kinematics of reaction time,
      movement time, movement unit and peak velocity. RESULTS: There were larger
      effects in favour of constraint-induced therapy on motor performance, daily
      function, and some aspects of reaching control compared with traditional
      rehabilitation. Children receiving constraint-induced therapy demonstrated higher
      scores for Peabody Developmental Motor Scale, Second Edition - Grasping (pretest
      mean +/- SD, 39.9 +/- 3.1; posttest, 44.1 +/- 2.8; P < 0.001), Pediatric Motor
      Activity Log (pretest, 1.8 +/- 0.3; posttest, 2.5 +/- 0.3; P < 0.001) and shorter
      reaction time, normalized movement time (P < 0.001) and higher peak velocity (P =
      0.004) of reaching movement. CONCLUSIONS: Constraint-induced therapy induced
      better grasping performance, daily function, and temporal and spatiotemporal
      control of reaching in children with unilateral cerebral palsy than traditional
      rehabilitation.

PMID- 22952305
TI  - Does neuromuscular electrical stimulation enhance the effectiveness of an
      exercise programme in subjects with knee osteoarthritis? A randomized controlled
      trial.
AB  - OBJECTIVE: To determine whether neuromuscular electrical stimulation applied to
      the quadriceps femoris muscle will enhance the effectiveness of an exercise
      programme in patients with knee osteoarthritis. DESIGN: A randomized trial with
      parallel intervention treatment groups. SETTING: Outpatient physical therapy
      clinic. SUBJECTS: Fifty participants (mean age (SD) 68.9 (7.7) years) with
      symptomatic idiopathic knee osteoarthritis and radiographic evidence (grade >= II
      Kelgren's classification). INTERVENTIONS: Participants were randomized into one
      of two groups receiving 12 biweekly treatments: An exercise-only group or an
      exercise combined with neuromuscular electrical stimulation group (biphasic
      pulses, at 75 Hz and 250 us phase duration). MAIN MEASURES: Knee pain intensity;
      maximal voluntary isometric contraction and voluntary activation of the
      quadriceps femoris muscle; measures of functional performance. RESULTS: A
      significant interaction effect (P = 0.01) indicated greater improvement in pain
      for the electrical stimulation group. The mean (SD) change in pain intensity was
      from 7.5 +/- 2 to 5 +/- 2.2 and from 7.4 +/- 1.9 to 3.3 +/- 2.4 in the exercise
      and electrical stimulation groups, respectively. A significant treatment effect
      was also noted for the voluntary activation of the quadriceps femoris, which
      increased by 22.2% in the electrical stimulation group and by 9.6% in the
      exercise group (P = 0.045). Significant improvements were observed in both groups
      in all remaining measures, with no differences between groups. CONCLUSIONS:
      Electrical stimulation treatment to the quadriceps femoris enhanced the
      effectiveness of an exercise programme in alleviating pain and improving
      voluntary activation in patients with knee osteoarthritis, but did not enhance
      its effect on muscle strength or functional performance.

PMID- 22952306
TI  - Feasibility of assessing the needs of stroke patients after six months using the
      GM-SAT.
AB  - OBJECTIVE: To investigate the feasibility of administering the Greater Manchester
      Stroke Assessment Tool (GM-SAT), a structured evidence-based needs assessment
      tool, in a community setting and its acceptability to stroke patients and their
      carers. SETTING: Community stroke services. SUBJECTS: One hundred and thirty
      seven stroke patients at six months post hospital discharge with no communication
      or cognitive difficulties residing in their own homes. INTERVENTION: Patients'
      needs were assessed by information, advice and support (IAS) coordinators from
      the UK Stroke Association using the GM-SAT. MAIN MEASURES: Number and nature of
      unmet needs identified and actions required to address these; patient/carer
      feedback; and IAS coordinator feedback. RESULTS: The mean number of unmet needs
      identified was 3 (min 0, max 14; SD 2.5). The most frequently identified unmet
      needs related to fatigue (34.3%), memory, concentration and attention (25.5%),
      secondary prevention non-lifestyle (21.9%) and depression (19.0%). It was found
      that 50.4% of unmet needs could be addressed through the provision of information
      and advice. Patients/carers found the assessment process valuable and IAS
      coordinators found the GM-SAT easy to use. CONCLUSIONS: Results demonstrate that
      the GM-SAT is feasible to administer in the community using IAS coordinators and
      is acceptable to patients and their carers, as well as staff undertaking the
      assessments. Further research is needed to determine whether the application of
      the GM-SAT at six months improves outcomes for patients.

PMID- 22952307
TI  - A systematic review on the pros and cons of using a pushrim-activated power
      assisted wheelchair.
AB  - OBJECTIVE: To determine the (dis)advantages of transition to a power-assisted
      wheelchair, and derive the clinical implications for its use or prescription.
      DATA SOURCES: Relevant articles published prior to May 2012 were identified using
      PubMed, Cochrane Library, REHABDATA, CIRRIE and CINAHL databases. REVIEW METHODS:
      Clinical or (randomized) controlled trials, published in a peer-reviewed journal,
      comparing power-assisted wheelchair use and hand-rim or powered wheelchair use
      were eligible. Data quality and validity were assessed by two reviewers
      independently using the Checklist for Measuring Quality developed by Downs and
      Black. RESULTS: A systematic search yielded 15 cross-over trails with repeated
      measurement design and one qualitative interview. Methodological quality scored
      between 9 and 15 points out of the maximum score of 32. Ten studies measuring
      body function and structure reported reduced strain on the arm and cardiovascular
      system during power-assisted propulsion compared to hand-rim propulsion. Twelve
      studies measuring activities and social participation reported precision tasks
      easier to perform with a hand-rim wheelchair and tasks which require more torque
      were easier with a power-assisted wheelchair. Social participation was not
      altered significantly by the use of a hand-rim, powered or power-assisted
      wheelchair. CONCLUSION: Power-assisted propulsion might be beneficial for
      subjects in whom independent hand-rim wheelchair propulsion is endangered by arm
      injury, insufficient arm strength or low cardiopulmonary reserves. Also, subjects
      who have difficulty propelling a wheelchair in a challenging environment can
      benefit from power-assisted wheelchair use. Caution is warranted for the
      additional width and weight in relation to the usual mode of transportation and
      access to the home environment.

PMID- 22952308
TI  - The burden and severity of illness due to 2009 pandemic influenza A (H1N1) in a
      large US city during the late summer and early fall of 2009.
AB  - In estimates of illness severity from the spring wave of the 2009 influenza A
      (H1N1) pandemic, reported case fatality proportions were less than 0.05%. In
      prior pandemics, subsequent waves of illness were associated with higher
      mortality. The authors evaluated the burden of the pandemic H1N1 (pH1N1) outbreak
      in metropolitan Atlanta, Georgia, in the fall of 2009, when increased influenza
      activity heralded the second wave of the pandemic in the United States. Using
      data from a community survey, existing surveillance systems, public health
      laboratories, and local hospitals, they estimated numbers of pH1N1-associated
      illnesses, emergency department (ED) visits, hospitalizations, intensive care
      unit (ICU) admissions, and deaths occurring in metropolitan Atlanta during the
      period August 16, 2009-September 26, 2009. The authors estimated 132,140
      pediatric and 132,110 adult symptomatic cases of pH1N1 in metropolitan Atlanta
      during the investigation time frame. Among children, these cases were associated
      with 4,560 ED visits, 190 hospitalizations, 51 ICU admissions, and 4 deaths.
      Among adults, they were associated with 1,130 ED visits, 590 hospitalizations,
      140 ICU admissions, and 63 deaths. The combined symptomatic case hospitalization
      proportion, case ICU admission proportion, and case fatality proportion were
      0.281%, 0.069%, and 0.024%, respectively. Influenza burden can be estimated using
      existing data and local surveys. The increased severity reported for subsequent
      waves in past pandemics was not evident in this investigation. Nevertheless, the
      second pH1N1 pandemic wave led to substantial numbers of ED visits,
      hospitalizations, and deaths in metropolitan Atlanta.

PMID- 22952310
TI  - Affective interactions in medical visits: ethnic differences among American
      Indian older adults.
AB  - OBJECTIVE: Investigate influence of ethnicity on older American Indian patients'
      interpretations of providers' affective behaviors. METHOD: Using data from 115
      older American Indian patients, random effects ordered logit models related
      patient ratings of providers' respect, empathy, and rapport first to separate
      measures of American Indian and White American ethnicity, then to "ethnic
      discordance," or difference between providers' and patients' cultural
      characteristics. RESULTS: In models accounting for patients' ethnicity only, high
      scores for American Indian ethnicity were linked to reduced evaluations for
      providers' respect; high scores on White ethnicity were associated with elevated
      ratings for empathy and rapport. In models accounting for provider-patient ethnic
      discordance, high discordance on either ethnicity scale was associated with
      reduced ratings for the same behaviors. DISCUSSION: Findings support "orthogonal
      ethnic identity" theory and extend "cultural health capital" theory, suggesting a
      pathway by which ethnicity becomes relevant to experience of health care among
      older adults.

PMID- 22952309
TI  - Long working hours and coronary heart disease: a systematic review and meta
      analysis.
AB  - The authors aggregated the results of observational studies examining the
      association between long working hours and coronary heart disease (CHD). Data
      sources used were MEDLINE (through January 19, 2011) and Web of Science (through
      March 14, 2011). Two investigators independently extracted results from eligible
      studies. Heterogeneity between the studies was assessed using the I(2) statistic,
      and the possibility of publication bias was assessed using the funnel plot and
      Egger's test for small-study effects. Twelve studies were identified (7 case
      control, 4 prospective, and 1 cross-sectional). For a total of 22,518
      participants (2,313 CHD cases), the minimally adjusted relative risk of CHD for
      long working hours was 1.80 (95% confidence interval (CI): 1.42, 2.29), and in
      the maximally (multivariate-) adjusted analysis the relative risk was 1.59 (95%
      CI: 1.23, 2.07). The 4 prospective studies produced a relative risk of 1.39 (95%
      CI: 1.12, 1.72), while the corresponding relative risk in the 7 case-control
      studies was 2.43 (95% CI: 1.81, 3.26). Little evidence of publication bias but
      relatively large heterogeneity was observed. Studies varied in size, design,
      measurement of exposure and outcome, and adjustments. In conclusion, results from
      prospective observational studies suggest an approximately 40% excess risk of CHD
      in employees working long hours.

PMID- 22952312
TI  - Bridging behavior and biology to reduce socioeconomic disparities in colorectal
      cancer risk.

PMID- 22952313
TI  - Childhood Graves disease masquerading as myasthenia gravis.
AB  - We report a child presenting with intermittent ophthalmoplegia and fluctuating
      ptosis and facial weakness whose evaluation revealed no evidence of myasthenia
      gravis but did reveal hyperthyroidism secondary to Graves disease. Successful
      treatment of the child's endocrinopathy resulted in complete resolution of his
      presenting symptoms. Children presenting with ophthalmoplegia and ptosis without
      proptosis should be evaluated for hyperthyroidism if no evidence of a myopathy or
      disorder of neuromuscular junction transmission is found. 

PMID- 22952311
TI  - Contribution of behavioral risk factors and obesity to socioeconomic differences
      in colorectal cancer incidence.
AB  - BACKGROUND: Health behaviors are known risk factors for colorectal cancer and are
      more common in low socioeconomic status (SES) populations. We evaluated the
      extent to which behavioral risk factors and body mass index (BMI) explain SES
      disparities in colorectal cancer incidence, overall and by tumor location.
      METHODS: We analyzed prospective National Institutes of Health-AARP Diet and
      Health Study data on 506 488 participants who were recruited in 1995-1996 from
      six US states and two metropolitan areas and followed through 2006. Detailed
      baseline data on risk factors for colorectal cancer, including health behaviors,
      were obtained using questionnaires. SES was measured by self-reported education
      and census-tract data. The outcome was primary incident invasive colorectal
      adenocarcinoma. Poisson regression was used to estimate the association between
      SES and risk of incident colorectal cancer, with adjustment for age, sex, race
      and ethnicity, family history, and state of residence. The model estimates were
      used to derive percentage mediation by behavioral risk factors; bias-corrected
      95% confidence intervals were obtained through bootstrap techniques. RESULTS:
      Seven-thousand six-hundred seventy-six participants developed colorectal cancer
      during follow-up. SES differences in prevalence of physical inactivity, unhealthy
      diet, smoking, and unhealthy weight each explained between 11.3% (BMI) and 21.6%
      (diet) of the association between education and risk of colorectal cancer and
      between 8.6% (smoking) and 15.3% (diet) of the association between neighborhood
      SES and risk of colorectal cancer. Health behaviors and BMI combined explained
      approximately 43.9% (95% CI = 35.1% to 57.9%) of the association of education and
      36.2% (95% CI = 28.0% to 51.2%) of the association of neighborhood SES with risk
      of colorectal cancer. The percentage explained by all factors and BMI combined
      was largest for right colon cancers and smallest for rectal cancers. CONCLUSION:
      A substantial proportion of the socioeconomic disparity in risk of new-onset
      colorectal cancer, and particularly of right colon cancers, may be attributable
      to the higher prevalence of adverse health behaviors in low-SES populations.

PMID- 22952314
TI  - Long-term neurodevelopmental follow-up of children with congenital muscular
      torticollis.
AB  - Congenital muscular torticollis is a common condition, but long-term
      neurodevelopmental follow-up is lacking. This study reports on neurodevelopmental
      outcome of 68 children, aged 7 to 9 years, with a history of congenital muscular
      torticollis, excluding children with torticollis due to other conditions. Thirty
      eight children were examined for presence of neurodevelopmental disorders.
      Telephone interview data were available for an additional 30 children. Of those
      examined, 22/38 (57.9%) had or were at risk for a developmental disorder
      (attention-deficit hyperactivity disorder (ADHD), developmental coordination
      disorder, language impairment, autistic spectrum disorder) on at least 1 of the
      assessments administered, 23/38 (60.5%) had received developmental treatment
      during childhood. One child, based on a telephone interview, had a history of
      developmental treatment. Therefore, 30/68 (44.1%) children of the total sample
      demonstrated a developmental delay/disorder, currently (22/68) or previously
      (8/68). Our findings suggest congenital muscular torticollis to be a significant
      risk factor for later neurodevelopmental conditions with disorders presenting at
      different stages of development. 

PMID- 22952315
TI  - Parent and self-report health-related quality of life measures in young patients
      with Tourette syndrome.
AB  - Tourette syndrome is a neurodevelopmental disorder characterized by tics and
      comorbid behavioral problems. This study compared child- and parent-reported
      quality of life and everyday functioning. We assessed 75 children with Tourette
      syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive
      disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities =
      4). All patients completed psychometric instruments, including the Gilles de la
      Tourette Syndrome-Quality of Life Scale for Children and Adolescents (child
      report) and the Child Tourette's Syndrome Impairment Scale (parent report). Data
      were compared for patients with pure Tourette syndrome, Tourette syndrome +
      obsessive-compulsive disorder, Tourette syndrome + attention-deficit
      hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no
      group differences in quality of life. However, there were differences for total,
      school, and home activities impairment scores. Children and parents may not share
      similar views about the impact of Tourette syndrome on functioning. The
      measurement of health-related quality of life in Tourette syndrome is more
      complex in children than adults. 

PMID- 22952316
TI  - Pathogenesis of pediatric multiple sclerosis.
AB  - Onset of multiple sclerosis in childhood occurs in 3-5% of patients. There is
      limited, but growing knowledge about the underlying pathobiology of pediatric MS.
      It is crucial to better understand this area in order to address central
      questions in the field: 1) Can pediatric multiple sclerosis inform us about
      factors related to disease initiation and propagation? 2) What are the biomarkers
      of disease course in pediatric multiple sclerosis; 3) Does pediatric multiple
      sclerosis pathogenesis differ from adult-onset multiple sclerosis; 4) How can we
      optimize treatment in pediatric demyelinating diseases? 5) Can pediatric multiple
      sclerosis provide insights into the environmental risk factors for multiple
      sclerosis in general? Here we review the current knowledge of the pathogenesis of
      multiple sclerosis in children, and address the five questions raised above.

PMID- 22952317
TI  - EACPR/AHA Scientific Statement. Clinical recommendations for cardiopulmonary
      exercise testing data assessment in specific patient populations.

PMID- 22952319
TI  - Ethical challenges in conducting HIV/AIDS research in correctional settings.
AB  - To explore ethical challenges in the conduct and oversight of HIV/AIDS research
      in correctional settings, 92 researchers; IRB chairs, members, and prisoner
      representatives; research ethicists; and prison administrators were asked the
      question, "If you had to pick the single most important ethical challenge to
      HIV/AIDS research with incarcerated people, what would it be?" Data were analyzed
      with NVivo 8.0 software and revealed that key concerns were confidentiality and
      privacy; autonomy and informed consent; and justice and access. Characteristics
      of people who are incarcerated, the nature of correctional institutions, and
      state and federal regulatory issues contributed to these challenges. These
      findings provide insights into ethical challenges that affect the conduct of
      HIV/AIDS research in correctional settings.

PMID- 22952318
TI  - Effect of 9p21.3 coronary artery disease locus neighboring genes on
      atherosclerosis in mice.
AB  - BACKGROUND: The human 9p21.3 chromosome locus has been shown to be an independent
      risk factor for atherosclerosis in multiple large-scale genome-wide association
      studies, but the underlying mechanism remains unknown. We set out to investigate
      the potential role of the 9p21.3 locus neighboring genes, including Mtap, the 2
      isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b, in atherosclerosis using
      knockout mice models. METHODS AND RESULTS: Gene-targeted mice for neighboring
      genes, including Mtap, Cdkn2a, p19Arf, and Cdkn2b, were each bred to mice
      carrying the human APO*E3 Leiden transgene that sensitizes the mice for
      atherosclerotic lesions through elevated plasma cholesterol. We found that the
      mice heterozygous for Mtap developed larger lesions compared with wild-type mice
      (49623+/-21650 versus 18899+/-9604 MUm(2) per section [mean+/-SD]; P=0.01), with
      morphology similar to that of wild-type mice. The Mtap heterozygous mice
      demonstrated changes in metabolic and methylation profiles and CD4(+) cell
      counts. The Cdkn2a knockout mice had smaller lesions compared with wild-type and
      heterozygous mice, and there were no significant differences in lesion size in
      p19Arf and Cdkn2b mutants compared with wild type. We observed extensive, tissue
      specific compensatory regulation of the Cdkn2a and Cdkn2b genes among the various
      knockout mice, making the effects on atherosclerosis difficult to interpret.
      CONCLUSIONS: Mtap plays a protective role against atherosclerosis, whereas Cdkn2a
      appears to be modestly proatherogenic. However, no relation was found between the
      9p21 genotype and the transcription of 9p21 neighboring genes in primary human
      aortic vascular cells in vitro. There is extensive compensatory regulation in the
      highly conserved 9p21 orthologous region in mice.

PMID- 22952320
TI  - Startle reactivity and prepulse inhibition of the acoustic startle response are
      modulated by catechol-O-methyl-transferase Val(158) Met polymorphism in adults
      with 22q11 deletion syndrome.
AB  - 22q11 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion
      on chromosome 22, which includes the gene coding for catechol-O-methyl
      transferase (COMT). High dopamine (DA) levels due to COMT haplo-insufficiency may
      be associated with the increased risk of developing schizophrenia in adults with
      22q11DS. Reduced prepulse inhibition (PPI) of the acoustic startle response has
      been associated with schizophrenia and with disrupted DAergic transmission in the
      prefrontal cortex (PFC). COMT Val(158)Met polymorphism has been shown to
      influence PPI. We report the first study in adults with 22q11DS to examine PPI of
      the acoustic startle response and its modulation by COMT Val(158)Met
      polymorphism. Startle reactivity (SR) and PPI of the acoustic startle response
      were measured in 23 adults with 22q11DS and 21 healthy controls. 22q11DS subjects
      were genotyped for the functional COMT Val(158)Met polymorphism. 22q11DS Met
      hemizygotes showed reduced SR and PPI compared with 22q11DS Val hemizygotes. The
      effect of COMT Val(158)Met polymorphism on PPI was no longer significant when
      controlling for baseline SR. Met hemizygosity in 22q11DS is associated with
      reduced SR and influences PPI indirectly. Decreased PFC functioning following
      excessive PFC DA levels may be one of the mechanisms by which the Met genotype in
      22q11DS disrupts SR.

PMID- 22952321
TI  - Collapsing glomerulopathy associated lupus in a black female with homozygous
      APOL1 mutation.
AB  - Collapsing glomerulopathy (CG), characterized by collapse of the glomerular
      capillary loops onto the mesangial stalks is rarely associated to systemic lupus
      erythematosus (SLE). Recently a genetic predisposition to HIV associated
      nephropathy (HIVAN) has been shown in Afro-Americans: MYH9 polymorhism in 2008
      and then APOL1 variants (G1 and G2 alleles) in 2010 were shown to be strongly
      associated with HIVAN. We describe here for the first time the association of CG
      in a young Afro-American female with SLE having a homozygous mutation of APOL1.
      The clinical history, laboratory findings and immunofluorescence all confirmed a
      diagnosis of SLE. However, studies for factors associated with collapsing
      glomerulopathy in other situations were consistently negative. As this Afro
      American patient developed a CG, we performed genotyping of APOL1. It was found
      that she is homozygotic for the G2 allele of APOL1. Despite.

PMID- 22952322
TI  - Autoimmune/inflammatory syndrome (ASIA) induced by biomaterials injection other
      than silicone medical grade.
AB  - BACKGROUND: Systemic autoimmune/granulomatous adverse reactions related to
      biomaterials other than silicone have rarely been reported. AIM: The aim of this
      paper is to communicate the cases of autoimmune/inflammatory syndrome induced by
      adjuvants (ASIA) in a study of Spanish patients suffering from inflammatory
      disorders related to biomaterial injections other than silicone, principally
      hyaluronic acid, acrylamides or methacrylate compounds. METHODS: The authors
      performed a retrospective analysis of the clinical, laboratory, histopathology
      and follow-up of a cohort of 250 cases of patients suffering from
      inflammatory/autoimmune disorders related to bioimplant injections. RESULTS: Of
      these 250 cases, patients with adverse reactions related to silicone injections
      (n = 65) were excluded. Of the remaining 185, 15 cases (8%) had systemic or
      distant and multiple complaints that could be categorized as ASIA. In all but
      four patients, inflammatory features at the implantation site preceded distant or
      systemic manifestations. Abnormal blood tests were common. Eleven cases (73.3%)
      with inflammatory localized nodules and panniculitis evolved into a variety of
      disorders, namely, primary biliary cirrhosis, Sjogren's syndrome, sarcoidosis,
      human adjuvant disease and inflammatory polyradiculopathy. Four cases presented
      primarily with systemic autoimmune disorders. CONCLUSIONS: Infrequently,
      biomaterials other than silicone can provoke local inflammatory adverse reactions
      that may evolve into systemic autoimmune and/or granulomatous disorders. Whether
      or not these biomaterials act as an adjuvant, they could be included in the ASIA
      category.

PMID- 22952323
TI  - The bereitschaftspotential in jerky movement disorders.
AB  - OBJECTIVE: To assess the diagnostic value of the bereitschaftspotential (BP) in
      jerky movement disorders. METHODS: A cross-sectional case series of 48 patients
      with psychogenic jerks, Gilles de la Tourette syndrome (GTS) or myoclonus was
      investigated. We measured the BP prior to the spontaneous jerk and voluntary
      wrist extension. In addition, the various jerky movements were imitated by 25
      healthy subjects. RESULTS: For patients with psychogenic jerks, we observed
      significantly more BPs; however, the BP was not identified prior to self-paced
      wrist extensions in 59% of cases. In contrast, none of the patients with the
      clinical diagnosis of myoclonus had a BP prior to their jerks but did have a BP
      prior to intentional wrist extension. In GTS, we demonstrated a BP in a minority
      of cases preceding motor tics and with a shorter duration in comparison with
      patients with psychogenic jerks. In healthy control subjects, a BP was found
      preceding all movements in all cases. The absence of a BP prior to intended wrist
      extension had a sensitivity of 0.59, specificity of 0.98 and positive likelihood
      ratio of 25 for the diagnosis of psychogenic jerks. CONCLUSIONS: We demonstrate
      that the BP can aid in the differentiation of jerky movements. Patients with
      psychogenic jerks significantly more often have a BP prior to their jerks and
      with a significantly earlier onset compared with GTS patients. A novel finding of
      our study is the absence of a BP prior to intentional movements for patients with
      psychogenic jerks. Validation in a prospective cohort is needed.

PMID- 22952324
TI  - Self-appraisal in behavioural variant frontotemporal degeneration.
AB  - OBJECTIVE: Previous work investigating deficits in self-appraisal in behavioural
      variant frontotemporal degeneration (bvFTD) has focused on a single domain:
      social/behavioural processes. We examined whether a domain-specific versus multi
      domain model best explains degraded self-appraisal in bvFTD. METHODS: 49 patients
      with bvFTD and 73 patients with Alzheimer's disease (AD) were administered
      quantitative assessments of episodic memory, naming and grammatical
      comprehension. Self-appraisal of cognitive test performance was assessed by
      asking patients to rate their performance immediately after completing each
      neuropsychological test. A discrepancy score was created to reflect the
      difference between patient performance on neuropsychological tests and self
      appraisal of their test performance. Self-appraisal for each neuropsychological
      measure was related to grey matter (GM) density in each group using voxel-based
      morphometry. RESULTS: bvFTD patients were poor at evaluating their own
      performance on all cognitive tests, with no significant correlations between self
      appraisal and actual performance. By contrast, poor self-appraisal in AD was
      restricted to episodic memory performance. Poor self-appraisal on each task in
      bvFTD and AD was related to reduced GM density in several ventral and rostral
      medial prefrontal regions. Crucially, poor self-appraisal for all domains in
      bvFTD was related to a specific area of reduced GM density in the subgenual
      cingulate (BA 25). CONCLUSION: Poor self-appraisal in bvFTD affects multiple
      domains, and this multi-domain impairment pattern is associated with frontal
      disease in the subgenual cingulate.

PMID- 22952325
TI  - Tremor in inflammatory neuropathies.
AB  - BACKGROUND: Tremor is known to occur in patients with neuropathies although its
      reported prevalence varies widely. Tremor has been shown to cause disability in
      children with Charcot-Marie-Tooth disease but no data exit about the disability
      caused by tremor in inflammatory neuropathies. Little is known about the response
      of neuropathic tremor to treatment and why it selectively occurs in some people
      and not others. METHODS: This case control study investigates the presence and
      severity of tremor in 43 consecutively recruited patients with inflammatory
      neuropathies at the National Hospital for Neurology and Neurosurgery, London.
      Clinical assessment, including Fahn-Tolosa-Marin Scale for tremor, sensory
      scores, power scores and Overall Neuropathy Limitations Scale, were recorded.
      Results of nerve conduction studies were retrieved and assessed. Nine patients'
      tremors were recorded with accelerometry. RESULTS: Tremor was most common in IgM
      paraproteinaemic neuropathies, as previously reported, but also occurred in 58%
      of those with chronic inflammatory demyelinating polyradiculoneuropathy and 56%
      of those with multifocal motor neuropathy with conduction block. We describe, for
      the first time, tremor in the majority of patients with multifocal motor
      neuropathy with conduction block. Tremor in all of these patients seems generally
      refractory to treatment except in a small number of cases where tremor improves
      with treatment of the underlying neuropathy. We provide evidence that tremor may
      add to disability in patients with inflammatory neuropathy. Mean tremor frequency
      was 6 Hz and did not vary with weight loading. We demonstrate for the first time
      that although tremor severity correlates with F wave latency, it is not
      sufficient to distinguish those with, from those without, tremor. CONCLUSION:
      Tremor in inflammatory neuropathies is common, adds to disability and yet does
      not often respond to treatment of the underlying neuropathy. When present, tremor
      severity is associated with F wave latency.

PMID- 22952327
TI  - The severity of cognitive deficits predicts return to work after a first-ever
      ischaemic stroke.
AB  - BACKGROUND: The inability of stroke patients to return to work contributes
      disproportionately to the socioeconomic impact of stroke and is best predicted by
      the severity of stroke. However, the role of cognitive deficits in stroke
      severity has not been scrutinised. We studied whether the initial cognitive
      severity of stroke, compared with other influential factors, predicts the
      inability to return to work after stroke. METHODS: Consecutive patients aged 18-
      65 with a first-ever ischaemic stroke, working full time previously, were
      assessed neuropsychologically within the first weeks after stroke and at the 6
      month follow-up. Similarly, 50 healthy demographic controls were assessed twice.
      The cognitive severity of stroke was operationalised as the number of initial
      cognitive deficits. Cognitive severity as a predictor of the inability to return
      to work was compared with demographic, occupational, neurological, radiological
      and functional data, vascular risk factors and mood state. RESULTS: The mean age
      of the 140 patients assessed both initially and at follow-up was 52 years. They
      had a mean of 13 years of education and 59% were men. At 6 months, only 41% of
      the patients had returned to work despite the relatively minor neurological and
      functional impairments of the cohort. In our model, the number of early cognitive
      deficits (OR=2.252, CI 1.294 to 3.918) was the only significant predictor of the
      inability to return to work. CONCLUSIONS: The initial cognitive severity of
      stroke predicts the later inability to return to work. The benefits of
      neuropsychological assessments within the first weeks after stroke are
      emphasised.

PMID- 22952326
TI  - Interferon beta for secondary progressive multiple sclerosis: a systematic
      review.
AB  - BACKGROUND: It is unclear whether recombinant beta interferons (IFNbeta) can be
      effective in secondary progressive multiple sclerosis (SPMS). The aim was to
      determine whether IFNbeta can reduce the risk of disability and cognitive
      impairment progression in SPMS. METHODS: Using Cochrane methodology, we reviewed
      all randomised placebo controlled trials of IFNbeta in SPMS patients (1995-March
      2012). RESULTS: 5 trials (3082 patients) were included. After 3 years,
      interferons did not reduce disability progression, confirmed at 6 months (RR
      0.98, 95% CI 0.82 to 1.16). A small reduction in the number of patients who had
      relapses during the first 3 years of treatment (RR 0.91, 0.84 to 0.97) was found.
      No analysis of cognitive data was possible. More treated than placebo patients
      dropped out for adverse events. CONCLUSION: 3 year treatment with IFNbeta does
      not delay permanent disability in SPMS but reduces relapse risk, indicating that
      the anti-inflammatory effect of IFNbeta is unable to prevent MS progression once
      it has become established.

PMID- 22952328
TI  - Surgical outcomes in patients with epileptogenic tumours and cavernomas in
      Sweden: good seizure control but late referrals.
AB  - PURPOSE: Seizure outcome after epilepsy surgery is to an important extent related
      to underlying aetiology. In this study of patients who underwent epilepsy surgery
      with a lesional aetiology in Sweden 1990-2004, the aim was to investigate seizure
      outcome and prognostic factors. METHODS: All patients operated on during the time
      period with a histopathological diagnosis of an epileptogenic tumour
      (ganglioglioma (GGL), dysembryoblastic neuroepithelial tumour (DNET) and low
      grade astrocytoma (AST)) or a cavernous haemangioma (CAH) were identified in the
      population based Swedish National Epilepsy Surgery Register. Univariate and
      multivariate analyses were performed to determine the independent contribution of
      the following variables to seizure outcome: age at surgery; epilepsy duration;
      preoperative seizure frequency; localisation of the resection; and
      histopathology. RESULTS: Of the 156 identified patients who had a 2 year follow
      up (103 adults and 53 children), 71% had temporal, 16% frontal and 13% parietal
      and occipital lobe resections. Mean presurgical epilepsy duration was 13 years in
      adults and 5 years in children. Main histopathological diagnosis was GGL or DNET
      in 67, CAH in 42 and AST in 47 patients. 77% of patients had sustained seizure
      freedom (with or without aura) 2 years after surgery. In the multivariate
      analysis, only diagnosis other than AST was independently associated with
      becoming seizure free. CONCLUSION: In this population based series, 120/156
      patients (77%) with epileptogenic tumours and cavernomas were seizure free 2
      years after surgery. Many had a very long epilepsy history. Seizure outcome can
      be improved if epilepsy surgery is considered earlier in patients with
      epileptogenic lesions.

PMID- 22952329
TI  - Parkinson's disease subtypes: lost in translation?
AB  - Like many neurodegenerative disorders, Parkinson's disease (PD) is clinically
      highly heterogeneous. A number of studies have proposed and defined subtypes of
      PD based on clinical features that tend to cluster together. These subtypes
      present an opportunity to refine studies of aetiology, course and treatment
      responsiveness in PD, as clinical variability must represent underlying
      biological or pathophysiological differences between individuals. In this paper,
      we review what subtypes have been identified in PD and the validation they have
      undergone. We then discuss what the subtypes could tell us about the disease and
      how they have been incorporated into studies of aetiology, progression and
      treatment. Finally, with the knowledge that they have been incorporated very
      little into PD clinical research, we make recommendations for how subtypes should
      be used and make some practical recommendations to address this lack of knowledge
      translation.

PMID- 22952330
TI  - Neurological picture. Anti-NMDA-receptor encephalitis: unusual presentation of an
      uncommon condition.

PMID- 22952331
TI  - Retraction: Epigenetic regulation of human cancer/testis antigen gene, HAGE, in
      chronic myeloid leukemia.

PMID- 22952332
TI  - CD20 has no prognostic significance in children with precursor B-cell acute
      lymphoblastic leukemia.

PMID- 22952333
TI  - Ethical concerns surrounding the conception of an HLA compatible child for
      medical purposes.

PMID- 22952334
TI  - Lenalidomide maintenance after allogeneic HSCT seems to trigger acute graft
      versus-host disease in patients with high-risk myelodysplastic syndromes or acute
      myeloid leukemia and del(5q): results of the LENAMAINT trial.

PMID- 22952336
TI  - Evaluating Maori community initiatives to promote healthy eating, healthy action.
AB  - Maori, the indigenous people of Aotearoa New Zealand, experience poorer health
      than non-Maori across a range of health measures. Interventions focused at an
      individual level have proved largely ineffective; 'bottom-up' approaches where
      communities determine their own priorities may be more sustainable than 'top
      down' approaches where goals are determined by health authorities. The purpose of
      this paper is to illustrate an innovative health promotion programme aimed at
      improving Maori health and to discuss the importance of ownership and control of
      health initiatives by Maori. Evaluators conducted a comprehensive evaluation of a
      Healthy Eating Healthy Action programme in six small Maori health agencies,
      gathering information from programme managers and co-ordinators, participants and
      wider community members about what changes were occurring at individual, family
      and community levels. Effective interventions built on cultural values and
      practices and were delivered by Maori with close connections to the community.
      Changes in nutrition and physical activity made by participants also benefitted
      their wider families and community. The changes demonstrated subtle but important
      shifts in thinking about healthy eating and healthy activity that in the longer
      term could lead to more measurable change towards improved quality of life for
      people within communities. 

PMID- 22952337
TI  - A realist-constructionist perspective on participatory research in health
      promotion.
AB  - Clarifying the contours of research in health promotion (HP) is an ongoing
      challenge. Research in this action-oriented field has traditionally been
      developed based on values such as participation and empowerment. Consequently,
      many forms of participatory research have emerged throughout the years, and
      participatory research has positioned itself as a core competency of HP and
      public health. This paper argues that participation as a normative stance guiding
      methodology, or as value, is a fragile posture upon which to position research
      practices. The argument is based on a realist-constructionist perspective of
      science and specifically uses Law and Latour's notion of inscription device and
      Callon's actor-network theory to suggest that participation is an epistemological
      necessity and that participatory research practices may be considered as
      inscription devices. These theoretical notions help clarify the consequences of
      participation on knowledge production. Finally, the article refers to Stengers's
      work to propose an ecology of research practices that defines obligations and
      exigencies for HP with respect to knowledge production and that are more
      consistent with the field's values of social justice and equity.

PMID- 22952338
TI  - Toward best-practice post-disaster mental health promotion for children: Sri
      Lanka.
AB  - There is a pressing need for low-cost intervention models to promote mental
      health among children in the wake of natural disasters. This article describes an
      evaluation of one such model: the Happy/Sad Letter Box (HSLB) Project, a mental
      health promotion intervention designed to minimize trauma in children, resulting
      from the Indian Ocean tsunami of 26 December 2004. The HSLB Project was
      implemented in 68 schools in Sri Lanka's Hambantota District from April 2005
      forward. Methods included questionnaires (n = 203), interviews, and group
      consultation with schoolchildren, teachers, teacher counsellors, principals,
      educational zone directors and parents. The HSLB intervention was seen as
      relevant and non-stigmatized, cost-effective if implemented after initial
      recovery steps, anecdotally effective in identifying and helping resolve trauma,
      accommodating the full range of children's daily stressors and sustainable.
      Gender, children's age, school size and the level of the tsunami impact for
      response were found to correlate with response differences. Along four dimensions
      previously identified in the literature (ability to triage, matching of
      intervention timing and focus, ability to accommodate a range of stressors and
      context compatibility), the HSLB Project is a promising intervention model (1)
      for children; (2) at group-level; (3) relating to natural disasters. The Nairobi
      Call to Action [WHO (2009) Nairobi Call to Action for Closing the Implementation
      Gap in Health Promotion. Geneva: World Health Organization] emphasized the
      importance of mainstreaming health promotion into priority programme areas,
      specifically including mental health. The HSLB Project represents the integration
      of health promotion practice into disaster preparedness mental health
      infrastructure. 

PMID- 22952340
TI  - Improvement in PET/CT image quality with a combination of point-spread function
      and time-of-flight in relation to reconstruction parameters.
AB  - The aim of this study was to investigate the effects of the point-spread function
      (PSF) and time-of-flight (TOF) on improving (18)F-FDG PET/CT images in relation
      to reconstruction parameters and noise-equivalent counts (NEC). METHODS: This
      study consisted of a phantom study and a retrospective analysis of 39 consecutive
      patients who underwent clinical (18)F-FDG PET/CT. The body phantom of the
      National Electrical Manufacturers Association and International Electrotechnical
      Commission with a 10-mm-diameter sphere was filled with an (18)F-FDG solution
      with a 4:1 radioactivity ratio compared with the background. The PET data were
      reconstructed with the baseline ordered-subsets expectation maximization (OSEM)
      algorithm, with the OSEM+PSF model, with the OSEM+TOF model, and with the
      OSEM+PSF+TOF model. We evaluated image quality by visual assessment, the signal
      to-noise ratio of the 10-mm sphere (SNR(10 mm)), the contrast of the 10-mm
      sphere, and the coefficient of variance in the phantom study and then determined
      the optimal reconstruction parameters. We also examined the effects of PSF and
      TOF on the quality of clinical images using the signal-to-noise ratio in the
      liver (SNR(liver)) in relation to the NEC in the liver (NEC(liver)). RESULTS: In
      the phantom study, the SNR(10 mm) was the highest for the OSEM+PSF+TOF model, and
      the highest value was obtained at iteration 2 for algorithms with the TOF and at
      iteration 3 for those without the TOF. In terms of a postsmoothing filter full
      width at half maximum (FWHM), the high SNR(10 mm) was obtained with no filtering
      or was smaller than 2 mm for algorithms with PSF and was 4-6 mm for those without
      PSF. The balance between the contrast recovery and noise is different for
      algorithms with either PSF or TOF. A combination of PSF and TOF improved SNR(10
      mm), contrast, and coefficient of variance, especially with a small-FWHM gaussian
      filter. In the clinical study, the SNR(liver) of the low-NEC(liver) group in the
      OSEM+PSF+TOF model was compared with that of the high-NEC(liver) group in
      conventional OSEM. The PSF+TOF improved the SNR(liver) by about 24.9% +/- 9.81%.
      CONCLUSION: A combination of PSF and TOF clearly improves image quality, whereas
      optimization of the reconstruction parameters is necessary to obtain the best
      performance for PSF or TOF. Furthermore, this combination has the potential to
      provide good image quality with either lower activity or shorter acquisition
      time, thus improving patient comfort and reducing the radiation burden.

PMID- 22952342
TI  - A new Tri-Fab bispecific antibody for pretargeting Trop-2-expressing epithelial
      cancers.
AB  - RS7 is an internalizing anti-Trop-2 pancarcinoma antibody capable of targeting
      most epithelial cancers. Because pretargeting strategies could improve the tumor
      localization of radionuclides, a new anti-Trop-2 * antihapten bispecific antibody
      for pretargeting, based on humanized RS7, was prepared and evaluated with a
      radiolabeled hapten-peptide in vitro and in vivo to determine whether its
      internalization properties would interfere with pretargeting. METHODS: The anti
      Trop-2 * antihapten bispecific antibody, TF12, was prepared using the modular
      dock-and-lock method. TF12 and humanized RS7 binding was assessed by cell binding
      assays and fluorescence-activated cell sorting analysis in a variety of human
      carcinoma cell lines. The internalization of TF12 was evaluated in vitro using a
      fluorescent TF12 conjugate or hapten-peptide and (111)In-labeled TF12 and RS7.
      The biodistribution of TF12 and its use as a pretargeting agent with an (111)In
      labeled hapten-peptide were assessed in several human epithelial cancer
      xenografts. Dose optimization was examined in 2 tumor models. RESULTS: TF12
      internalizes, but a substantial fraction remained accessible on the tumor
      surface. Fluorescence-activated cell sorting analysis showed only a minor change
      in fluorescent signal when the tumor was probed with a fluorescent hapten-peptide
      over 4 h, and microscopy showed substantial membrane staining when reassessed at
      24 h after TF12 exposure. Only 40.1% of (111)In-TF12 was internalized after 24 h.
      In vivo, excellent tumor localization of the (111)In-labeled peptide was observed
      in several tumor models. CONCLUSION: TF12 was retained sufficiently on the cell
      surface in several epithelial cancers, thereby making it suitable for pretargeted
      imaging and therapy of various Trop-2-expressing carcinomas.

PMID- 22952343
TI  - Predicting nonsentinel lymph node metastasis using lymphoscintigraphy in patients
      with breast cancer.
AB  - Several models for predicting the likelihood of nonsentinel lymph node (NSLN)
      metastasis using histopathologic parameters in sentinel-positive breast cancer
      patients have been proposed. In this study, we established a new model that uses
      sentinel lymphoscintigraphic findings and histopathologic parameters as
      covariates and assessed its predictive performance. METHODS: The analysis
      included breast cancer patients (n = 301 women) who underwent sentinel
      lymphoscintigraphy (SLS) using (99m)Tc-labeled human serum albumin, had sentinel
      lymph node biopsy results positive for metastasis, and subsequently underwent
      complete axillary lymph node dissection. First, we devised a grading system
      relating SLS patterns to the risk of NSLN metastasis positivity. Second, we
      developed a multivariate logistic regression model for the prediction of NSLN
      metastasis using the SLS pattern and histopathologic parameters as covariates and
      compared its performance with that of the extensively validated Memorial Sloan
      Kettering Cancer Center model using receiver-operating-characteristic curve
      analysis. RESULTS: The SLS visual grade was strongly correlated with the presence
      of NSLN metastases. A well-calibrated prediction model for NSLN metastasis was
      constructed using SLS grade and histopathologic findings. The mean area under the
      curve of our model was 0.812, which is significantly greater than that of the
      Memorial Sloan-Kettering Cancer Center model (P < 0.001). A nomogram was drawn to
      facilitate the application of our model. CONCLUSION: SLS can aid in predicting
      NSLN metastasis in patients with breast cancer. Our model performed better than
      did established prediction models.

PMID- 22952344
TI  - Circulating miRNAs as surrogate markers for circulating tumor cells and
      prognostic markers in metastatic breast cancer.
AB  - PURPOSE: The use of circulating tumor cells (CTC) as a prognostic marker in
      metastatic breast cancer (MBC) has been well established. However, their efficacy
      and accuracy are still under scrutiny mainly because of methods of their
      enrichment and identification. We hypothesized that circulating miRNAs can
      predict the CTC status of patients with MBC, and tested for the same.
      Furthermore, we aimed at establishing a panel of circulating miRNAs capable of
      differentiating MBC cases from healthy controls. EXPERIMENTAL DESIGN: Circulating
      miRNAs from plasma of CTC-positive and CTC-negative patients with MBC, and
      healthy controls, were profiled by TaqMan Human MicroRNA arrays. Candidates from
      the initial screen were validated in an extended cohort of 269 individuals (61
      CTC-positive, 72 CTC-negative, 60 CTC-low MBC cases, and 76 controls). RESULTS:
      CTC-positive had significantly higher levels of miR-141, miR-200a, miR-200b, miR
      200c, miR-203, miR-210, miR-375, and miR-801 than CTC-negative MBC and controls
      (P < 0.00001), whereas miR-768-3p was present in lower amounts in MBC cases (P <
      0.05). miR-200b was singled out as the best marker for distinguishing CTC
      positive from CTC-negative patients (AUC 0.88). We identified combinations of
      miRNAs for differentiating MBC cases from controls (AUC 0.95 for CTC-positive;
      AUC 0.78 for CTC-negative). Combinations of miRNAs and miR-200b alone were found
      to be promising prognostic marker for progression-free and overall survival.
      CONCLUSION: This is the first study to document the capacity of circulating
      miRNAs to indicate CTC status and their potential as prognostic markers in
      patients with MBC.

PMID- 22952345
TI  - Serum lactate dehydrogenase is prognostic for survival in patients with bone
      metastases from breast cancer: a retrospective analysis in bisphosphonate-treated
      patients.
AB  - PURPOSE: Survival is highly variable in women with bone metastases from breast
      cancer and prognostic factors are needed. We analyzed data from a phase III trial
      comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer
      and bone metastases to identify variables prognostic for overall survival.
      EXPERIMENTAL DESIGN: Patients who received ZOL (n = 435) with bone marker
      assessments and complete baseline data were included. Relative risks (RR) of
      death over 24 months were assessed using a stratified Cox regression analysis. A
      reduced model was generated using stepwise backward elimination until only
      significant (P < 0.05) variables remained. RESULTS: Only 5 of 19 variables
      analyzed remained significantly prognostic for survival in the reduced
      multivariate model. These included age more than 50 years (RR 1.78-2.53, P <=
      0.01 for each decade >50 versus <= 50); Functional Assessment of Cancer Therapy
      General (FACT-G) score less than 65 units (P < 0.05 vs. >= 75 units); impaired
      (PS >= 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG)
      performance status (RR 1.74, P < 0.01); prior versus no prior chemotherapy (RR
      1.97; P < 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase >=
      upper limit of normal (ULN) but < 2 * ULN correlated with a two-fold increased
      risk of death, and LDH > 2 * ULN correlated with a six-fold increased risk of
      death versus LDH < ULN (P < 0.0001 for both). Baseline bone marker levels were
      not significantly correlated with survival after adjustment for other significant
      covariates. CONCLUSIONS: This retrospective analysis shows that LDH levels
      correlate strongly with survival in patients with bone metastases from breast
      cancer and confirms the relevance of previously described prognostic factors.

PMID- 22952346
TI  - Molecular pathways: tumor cells Co-opt the brain-specific metabolism gene CPT1C
      to promote survival.
AB  - The metabolic adaptations of cancer cells are receiving renewed attention as
      potential targets for therapeutic exploitation. Recent work has highlighted the
      importance of fatty acid catabolism through beta-oxidation to cellular energy
      homeostasis. In this article, we describe recent preclinical studies suggesting
      that a gene usually expressed only in the brain, carnitine palmitoyltransferase
      (CPT)1C, promotes cancer cell survival and tumor growth. CTP1C confers rapamycin
      resistance on breast cancer cells, indicating that this gene may act in a pathway
      parallel to mTOR-enhanced glycolysis. Because of CPT1C's normally brain
      restricted expression and the inability of most drugs to pass the blood-brain
      barrier, CPT1C may be an ideal candidate for specific small-molecule inhibition.
      We further speculate that concurrent targeting of CPT1C activity and glycolysis
      in tumor cells could be a highly effective anticancer approach.

PMID- 22952347
TI  - Anti-DLL4 has broad spectrum activity in pancreatic cancer dependent on targeting
      DLL4-Notch signaling in both tumor and vasculature cells.
AB  - PURPOSE: We previously showed that targeting Delta-like ligand 4 (DLL4) in colon
      and breast tumors inhibited tumor growth and reduced tumor initiating cell
      frequency. In this report, we have extended these studies to pancreatic cancer
      and probed the mechanism of action in tumor and stromal cells involved in
      antitumor efficacy. EXPERIMENTAL DESIGN: Patient-derived pancreatic xenograft
      tumor models were used to evaluate the antitumor effect of anti-DLL4. To
      investigate the mechanism of action, we compared the activity of targeting DLL4
      in tumor cells with an anti-human DLL4 antibody (anti-hDLL4) and in the host
      stroma/vasculature with an anti-mouse DLL4 antibody (anti-mDLL4). The effect of
      these antibodies on cancer stem cell frequency was examined by in vivo limiting
      dilution assays. RESULTS: The combination of anti-hDLL4 and anti-mDLL4 was
      efficacious in a broad spectrum of pancreatic tumor xenografts and showed
      additive antitumor activity together with gemcitabine. Treatment with either anti
      hDLL4 or anti-mDLL4 delayed pancreatic tumor recurrence following termination of
      gemcitabine treatment, and the two together produced an additive effect. Anti
      hDLL4 had a pronounced effect in reducing the tumorigenicity of pancreatic cancer
      cells based on serial transplantation and tumorsphere assays. In contrast,
      disruption of tumor angiogenesis with anti-mDLL4 alone or with anti-VEGF had
      minimal effects on tumorigenicity. Gene expression analyses indicated that anti
      DLL4 treatment regulated genes that participate in Notch signaling, pancreatic
      differentiation, and epithelial-to-mesenchymal transition. CONCLUSIONS: Our
      findings suggest a novel therapeutic approach for pancreatic cancer treatment
      through antagonism of DLL4/Notch signaling.

PMID- 22952348
TI  - Quantifying the added value of a diagnostic test or marker.
AB  - In practice, the diagnostic workup usually starts with a patient with particular
      symptoms or signs, who is suspected of having a particular target disease. In a
      sequence of steps, an array of diagnostic information is commonly documented. The
      diagnostic information conveyed by different results from patient history,
      physical examination, and subsequent testing is to varying extents overlapping
      and thus mutually dependent. This implies that the diagnostic potential of a test
      or biomarker is conditional on the information obtained from previous tests. A
      key question about the accuracy of a diagnostic test/biomarker is whether that
      test improves the diagnostic workup beyond already available diagnostic test
      results. This second report in a series of 4 gives an overview of several methods
      to quantify the added value of a new diagnostic test or biomarker, including the
      area under the ROC curve, net reclassification improvement, integrated
      discrimination improvement, predictiveness curve, and decision curve analysis.
      Each of these methods is illustrated with the use of empirical data. We reiterate
      that reporting on the relative increase in discrimination and disease
      classification is relevant to obtain insight into the incremental value of a
      diagnostic test or biomarker. We also recommend the use of decision-analytic
      measures to express the accuracy of an entire diagnostic workup in an informative
      way.

PMID- 22952349
TI  - Calcium, magnesium, albumin, and total protein measurement in serum as assessed
      with 20 fresh-frozen single-donation sera.

PMID- 22952350
TI  - Sister Mary Joseph's nodule.

PMID- 22952351
TI  - Amiodarone-induced hair loss: case report and review of the literature.

PMID- 22952352
TI  - Fatal alveolar hemorrhage due to Kaposi sarcoma.

PMID- 22952353
TI  - Effects of co-grazing dairy heifers with goats on animal performance, dry matter
      yield, and pasture forage composition.
AB  - Mixed livestock grazing can offer an alternative management system for rearing
      dairy replacement heifers (Bos taurus). A 2-yr study was conducted during 2009
      (yr 1) and 2010 (yr 2) to determine the effects of co-grazing Holstein heifers
      under rotational stocking with Boer * Kiko goats on animal performance, pasture
      DM yield, and botanical composition. Each year, 24 heifers (134 +/- 6 d of age
      and 147.4 +/- 31.2 kg BW in yr 1; 166 +/- 11 d of age and 168.0 +/- 27.6 kg BW in
      yr 2) and 6 goats (2 yr old and 39.7 +/- 16.2 kg BW in yr 1; 1 yr old and 33.7 +/
      7.4 kg BW in yr 2) were divided into 6 paddocks with 4 heifers and 2 goats,
      where applicable, per group. Low endophyte-infected tall fescue (Festuca
      arundinacea Schreb.) and white clover (Trifolium repens L.) pastures were used to
      evaluate 2 grazing strategies (heifers grazed alone [HO] or heifers co-grazed
      with goats [HG]). In addition, 6 goats were assigned to 2 paddocks and grazed
      alone (GO) each year to estimate goat pasture forage intake and compare
      Haemonchus contortus infection to co-grazed goats. Forage samples were taken
      monthly to assess DM yield and botanical composition. Samples collected for
      botanical composition were manually sorted into grass, legume, and weed species.
      Forage DMI was estimated using a rising plate meter before and after grazing.
      Heifer BW at the conclusion of yr 1 and yr 2 did not differ between HO and HG (P
      = 0.40 and P = 0.12, respectively). Likewise, overall ADG did not differ between
      HO and HG, averaging 0.65 kg/d and 0.63 kg/d over both grazing seasons (P =
      0.70). Grazing strategy did not affect forage or total DMI in yr 1; however, HO
      consumed 2.3 kg/d more forage DM than HG (P < 0.01), resulting in greater total
      DMI for HO in yr 2 (P < 0.01). Heights at the hip and withers were greater for HO
      than for HG during both grazing seasons (P < 0.05). Weed presence did not differ
      between grazing strategies over both grazing seasons as determined by manual
      harvesting, but visual estimation of botanical composition at the end of yr 2
      showed that HO paddocks had 3.5 times more weed presence than HG pastures (P <
      0.01). Within the confines of this study, co-grazing did not affect overall
      heifer BW gain, but it decreased DMI, suggesting that dairy heifers can be co
      grazed with goats without negative effects on ADG or feed efficiency.

PMID- 22952354
TI  - National Beef Quality Audit-2011: Survey of instrument grading assessments of
      beef carcass characteristics.
AB  - The instrument grading assessments for the 2011 National Beef Quality Audit
      evaluated seasonal trends of beef carcass quality and yield attributes over the
      course of the year. One week of instrument grading data, HCW, gender, USDA
      quality grade (QG), and yield grade (YG) factors, were collected every other
      month (n = 2,427,074 carcasses) over a 13-mo period (November 2010 through
      November 2011) from 4 beef processing corporations, encompassing 17 federally
      inspected beef processing facilities, to create a "snapshot" of carcass quality
      and yield attributes and trends from carcasses representing approximately 8.5% of
      the U.S. fed steer and heifer population. Mean yield traits were YG (2.86), HCW
      (371.3 kg), fat thickness (1.19 cm.), and LM area (88.39 cm(2)). The YG
      distribution was YG 1, 15.7%; YG 2, 41.0%; YG 3, 33.8%; YG 4, 8.5%; and YG 5,
      0.9%. Distribution of HCW was <272.2 kg, 1.6%; 272.2 to 453.6 kg, 95.1%; and
      >=453.6 kg, 3.3%. Monthly HCW means were November 2010, 381.3 kg; January 2011,
      375.9 kg; March 2011, 366.2 kg; May 2011, 357.9 kg; July 2011, 372.54 kg;
      September 2011, 376.1 kg; and November 2011, 373.5 kg. The mean fat thickness for
      each month was November 2010, 1.30 cm; January 2011, 1.22 cm; March 2011, 1.17
      cm; May 2011, 1.12 cm; July 2011, 1.19 cm; September 2011, 1.22 cm; and November
      2011, 1.22 cm. The overall average marbling score was Small(49). The USDA QG
      distribution was Prime, 2.7%; Top Choice, 22.9%; Commodity Choice, 38.6%; and
      Select, 31.5%. Interestingly, from November to May, seasonal decreases (P <
      0.001) in HCW and fat thicknesses were accompanied by increases (P < 0.001) in
      marbling. These data present the opportunity to further investigate the entire
      array of factors that determine the value of beef. Data sets using the online
      collection of electronic data will likely be more commonly used when evaluating
      the U.S. fed steer and heifer population in future studies.

PMID- 22952355
TI  - Marker type but not concentration influenced apparent ileal amino acid
      digestibility in phytase-supplemented diets for broiler chickens and pigs.
AB  - Two experiments were conducted to investigate whether the choice of digestibility
      marker or marker concentration in corn-soybean meal diets influence apparent
      ileal AA digestibility (AIAAD) or the potential phytase-induced improvement in
      AIAAD in broiler chickens and pigs. One hundred ninety-two, 42-d-old, Ross 708
      broilers were used in a 7-d study in Exp 1. The birds were allocated to 6 dietary
      treatments in a 2 * 3 factorial arrangement of treatments in a split-plot design.
      The factors were a combination of chromic oxide and titanium dioxide (0.3% or
      0.5% of both markers, as-fed basis), and 3 levels of phytase inclusion [0, 500,
      or 1,000 phytase units (FTU)/kg]. In Exp. 2, 6 barrows fitted with a simple T
      cannula at the distal ileum were allocated to 4 diets in a 6 * 4 Youden square
      design and 2 * 2 factorial arrangement of treatments. The factors were similar to
      Exp. 1, except the 500-FTU/kg phytase level was not used in Exp. 2. There were no
      marker type * marker concentration, phytase * marker type, or phytase * marker
      type * marker concentration interactions for any of the AA in either experiment.
      On average, AIAAD values calculated using Ti was greater (P < 0.05) than those
      calculated using Cr, regardless of the phytase inclusion level in both
      experiments. In Exp. 1, AIAAD values for His, Trp, Cys, and Pro were greater (P <
      0.05) at the 0.3% than 0.5% marker concentration. The AIAAD values were
      consistently greater when calculated using Ti compared with Cr, irrespective of
      phytase level. It is concluded that the type of marker used does not influence
      whether a response to phytase supplementation, in terms of AIAAD, is observed.

PMID- 22952356
TI  - Influence of feeding increasing levels of dry corn distillers grains plus
      solubles in whole corn grain-based finishing diets on total tract digestion,
      nutrient balance, and excretion in beef steers.
AB  - Four crossbred steers (average BW = 478 +/- 33 kg) were used in a 4 * 4 Latin
      square design to determine the effects of dietary concentration of dry corn
      distillers grains plus solubles (DDGS) in whole corn-based finishing diets on
      total tract digestion and nutrient balance and excretion. The DDGS were fed at 0%
      (control), 16.7%, 33.3%, and 50% of dietary DM. All diets contained 10% (DM
      basis) alfalfa/grass haylage and were formulated to meet or exceed the estimated
      requirements for CP. Steers were fed the experimental diets ad libitum for a 14-d
      adaptation period followed by a 5-d period for fecal and urine collection.
      Increasing concentration of DDGS in diets from 0 to 50% of DM linearly decreased
      (P < 0.05) total tract DM and starch digestibility (from 77.8 to 72.9%, and 89.2
      to 81.5%, respectively). Daily N and P intakes linearly increased (P = 0.06 and P
      = 0.01, respectively) with increasing DDGS concentration. Fecal and urinary N, P,
      S, Mg, and K excretion linearly increased (P < 0.05) with increasing DDGS
      concentration; however, Se and Na excretion did not differ (P > 0.38) among
      treatments. Retention (g/d; intake minus urinary and fecal excretion) of N did
      not differ (P > 0.16) among treatments. Retention of P tended (P = 0.07) to
      linearly increase and retention of S (g/d) linearly increased (P = 0.004), with
      increasing DDGS concentration. There were no effects (P > 0.16) of dietary
      treatment on digestion and retention of Se, Mg, K, and Na. Plasma P and S
      concentrations increased (P = 0.03 and 0.01, respectively) with increasing DDGS
      concentration. These data indicate that feeding DDGS up to 50% of dietary DM in
      whole corn grain-based finishing diets does not have a negative effect on
      nutrient retention but decreases digestibility. Total excretion of N, P, Ca, Mg,
      S, and K increased as DDGS concentration increased.

PMID- 22952357
TI  - Breed and breed x environment interaction effects for growth traits and survival
      rate from birth to weaning in crossbred lambs.
AB  - This study was conducted to estimate the effects of sire breed (Charollais,
      Dorper, Dorset, Hampshire, and Suffolk) and genetic group of the dam [local
      whiteface (Criolla), grade Hampshire, grade Suffolk, F(1) Dorper * Pelibuey,
      Australian composite, hair sheep (Barbados Blackbelly or Pelibuey), Dorset,
      Hampshire and Suffolk] on birth weight, survival rate from birth to weaning, and
      weaning weight adjusted to 65 d of age. Data were recorded from 2004 to 2006 on
      crossbreed lambs obtained by artificial insemination from 114 flocks in Central
      Mexico. High (above the mean) or low (below the mean) environmental categories
      were assigned to each record from flock-year-season effects solutions obtained in
      fixed-effects linear model analyses. Birth weights of lambs sired by Charollais
      rams (3.94 kg) were heavier (P < 0.05) than those sired by Suffolk (3.69 kg)
      whereas Dorper-, Dorset-, and Hampshire-sired lambs were intermediate. For
      weaning weight, lambs sired by Charollais were the heaviest (19.16 kg) compared
      with lambs sired by Hampshire (17.86 kg), Suffolk (17.79 kg), and Dorper (17.28
      kg) whereas Dorset sired were the lightest (16.77 kg; P < 0.05). Lambs sired by
      Dorset rams had a lower survival rate (77.1%) than lambs sired by Charollais,
      Dorper, Hampshire, or Suffolk (81.6 to 83.3%; P < 0.05). Lambs from Australian
      composite, Dorset, Hampshire, and Suffolk dams were heavier for birth and weaning
      compared with lambs from local whiteface (Criolla), hair sheep breeds (Barbados
      Blackbelly or Pelibuey), or crosses (F(1) Pelibuey * Dorper) dams (P < 0.05)
      whereas lambs from grade Hampshire and grade Suffolk were intermediate. The
      genetic group of the dam had no effect (P > 0.05) on survival rate. Sire breed *
      environmental category interaction effect was significant for birth weight (P <
      0.01) and weaning weight (P < 0.05), but relatively small changes on the ranking
      of sire breeds were observed between environmental categories for weaning weight.
      Genetic group of the dam * environmental category interaction effect was
      significant for birth and weaning weights (P < 0.01). Weaning weight of lambs
      from hair sheep breeds (Barbados Blackbelly or Pelibuey) and crosses (F(1)
      Pelibuey * Dorper) as well as purebred Dorset, Hampshire, and Suffolk dams were
      more affected when changing from the high to the low environmental category
      compared with the other genetic groups. No breed of the sire or genetic group of
      the dam * environmental category interactions were (P > 0.05) observed for
      survival rate.

PMID- 22952359
TI  - Board invited review: The importance of the gestation period for welfare of
      calves: maternal stressors and difficult births.
AB  - The prenatal period is of critical importance in defining how individuals respond
      to their environment throughout life. Stress experienced by pregnant females has
      been shown to have detrimental effects on offspring biology in humans and a
      variety of other species. It also is becoming increasingly apparent that prenatal
      events can have important consequences for the behavior, health, and productivity
      of offspring in farmed species. Pregnant cattle may experience many potentially
      important stressors, for instance, relating to their social environment, housing
      system and physical environment, interactions with humans and husbandry
      procedures, and their state of health. We examined the available literature to
      provide a review of the implications of prenatal stress for offspring welfare in
      cattle. The long-term effects of dystocia on cattle offspring also are reviewed.
      To ensure a transparent and repeatable selection process, a systematic review
      approach was adopted. The research literature clearly demonstrates that prenatal
      stress and difficult births in beef and dairy cattle both have implications for
      offspring welfare and performance. Common husbandry practices, such as transport,
      were shown to influence offspring biology and the importance of environmental
      variables, including thermal stress and drought, also were highlighted. Maternal
      disease during pregnancy was shown to negatively impact offspring welfare.
      Moreover, dystocia-affected calves suffer increased mortality and morbidity,
      decreased transfer of passive immunity, and important physiological and
      behavioral changes. This review also identified considerable gaps in our
      knowledge and understanding of the effects of prenatal stress in cattle.

PMID- 22952360
TI  - Amino acid digestibility in canola, cottonseed, and sunflower products fed to
      finishing pigs.
AB  - Our objective was to determine the standardized ileal digestibility (SID) of CP
      and AA in soybean meal (SBM) and canola, cotton, and sunflower products fed to
      finishing pigs. Each of 8 barrows (average initial BW = 106.6 +/- 5.5 kg) were
      surgically fitted with a T-cannula in the distal ileum. Pigs were allotted to an
      8 * 8 Latin square design with 8 diets and 8 periods. The 7 protein ingredients
      were canola seeds (CS), canola meal (CM), cottonseed meal (CSM), sunflower seeds
      (SFS), sunflower meal (SFM), dehulled sunflower meal (SFM-DH), and SBM, with each
      ingredient included as the sole source of AA in the diet. A N-free diet was used
      to estimate basal endogenous losses of AA. Among tested ingredients, SBM had the
      greatest (P < 0.05) SID of Lys, and CS had the least (P < 0.05) SID of Phe, Thr,
      and Tyr. The SID of all indispensable AA except Trp was less (P < 0.05) in CS
      than SBM, and CM had a greater (P < 0.05) SID of all indispensable AA except Arg,
      His, Lys, and Trp than CS. However, the SID of all indispensable AA except Arg
      and Trp were less (P < 0.05) in CM than in SBM. The SID of all indispensable AA
      except Arg and Trp also were less (P < 0.05) in CSM than in SBM, and the SID of
      Met was less (P < 0.05) in CSM than in all other ingredients. Among sunflower
      products, the SID of His, Leu, Phe, and Thr were less (P < 0.05) in SFM-DH than
      in SFS and SFM, and the SID of Ile, Met, and Val were less (P < 0.05) in SFM-DH
      than in SFS; however, for CP, Arg, Lys, and Trp, no differences among SFS, SFM,
      and SFM-DH were observed. The SID of all indispensable AA except Trp were less (P
      < 0.05) in SFM-DH than SBM, and the SID of His, Ile, Lys, Thr, and Val in SFM
      were also less (P < 0.05) than in SBM. Except for Lys, no differences between SBM
      and SFS were observed. In conclusion, the SID of most AA in CS, CM, CSM, SFM, and
      SFM-DH are less than in SBM.

PMID- 22952361
TI  - Carbon footprint and ammonia emissions of California beef production systems.
AB  - Beef production is a recognized source of greenhouse gas (GHG) and ammonia
      (NH(3)) emissions; however, little information exists on the net emissions from
      beef production systems. A partial life cycle assessment (LCA) was conducted
      using the Integrated Farm System Model (IFSM) to estimate GHG and NH(3) emissions
      from representative beef production systems in California. The IFSM is a process
      level farm model that simulates crop growth, feed production and use, animal
      growth, and the return of manure nutrients back to the land to predict the
      environmental impacts and economics of production systems. Ammonia emissions are
      determined by summing the emissions from animal housing facilities, manure
      storage, field applied manure, and direct deposits of manure on pasture and
      rangeland. All important sources and sinks of methane, nitrous oxide, and carbon
      dioxide are predicted from primary and secondary emission sources. Primary
      sources include enteric fermentation, manure, cropland used in feed production,
      and fuel combustion. Secondary emissions occur during the production of resources
      used on the farm, which include fuel, electricity, machinery, fertilizer, and
      purchased animals. The carbon footprint is the net exchange of all GHG in carbon
      dioxide equivalent (CO(2)e) units per kg of HCW produced. Simulated beef
      production systems included cow-calf, stocker, and feedlot phases for the
      traditional British beef breeds and calf ranch and feedlot phases for Holstein
      steers. An evaluation of differing production management strategies resulted in
      ammonia emissions ranging from 98 +/- 13 to 141 +/- 27 g/kg HCW and carbon
      footprints of 10.7 +/- 1.4 to 22.6 +/- 2.0 kg CO(2)e/kg HCW. Within the British
      beef production cycle, the cow-calf phase was responsible for 69 to 72% of total
      GHG emissions with 17 to 27% from feedlot sources. Holstein steers that entered
      the beef production system as a by-product of dairy production had the lowest
      carbon footprint because the emissions associated with their mothers were
      primarily attributed to milk rather than meat production. For the Holstein
      system, the feedlot phase was responsible for 91% of the total GHG emission,
      while the calf-ranch phase was responsible for 7% with the remaining 2% from
      transportation. This simulation study provides baseline emissions data for
      California beef production systems and indicates where mitigation strategies can
      be most effective in reducing emissions.

PMID- 22952362
TI  - Effects of temperament and acclimation to handling on feedlot performance of Bos
      taurus feeder cattle originated from a rangeland-based cow-calf system.
AB  - Two experiments evaluated the effects of temperament and acclimation to handling
      on performance of Angus * Hereford feeder cattle reared in extensive rangeland
      systems until weaning. In Exp. 1, 200 calves (n = 97 for yr 1; n = 103 for yr 2)
      were evaluated for temperament at weaning (average age +/- SE = 152 +/- 1 d) by
      chute score and exit velocity. Chute score was assessed on a 5-point scale
      according to behavior during chute restraining. Exit score was calculated by
      dividing exit velocity into quintiles and assigning calves a score from 1
      (slowest) to 5 (fastest). A temperament score was calculated for each calf by
      averaging chute and exit scores. Calf temperament was classified according to
      temperament score as adequate (<=3) or excitable (>3). After weaning, calves were
      assigned to a 40-d preconditioning followed by growing (139 d) and finishing (117
      d) phases until slaughter. Weaning BW was decreased (P = 0.04) in excitable
      calves compared with adequate calves. No differences were detected (P >= 0.21)
      for ADG during preconditioning, growing, and finishing phases; hence, excitable
      calves tended (P = 0.09) to have decreased HCW compared with adequate calves. In
      Exp. 2, 60 steers (initial age +/- SE = 198 +/- 2 d) were weighed and evaluated
      for temperament score 35 d after weaning (d -29). On d -28, steers were ranked by
      these variables and assigned to receive an acclimation treatment or not
      (control). Acclimated steers were processed through a handling facility twice
      weekly for 4 wk (d -28 to -1) whereas control steers remained undisturbed on
      pasture. On d 0, all steers were transported for 24 h and returned to the
      research facility (d 1). On arrival, steers were ranked by BW within treatment
      and randomly assigned to 20 feedlot pens for a 28-d feedlot receiving period.
      Acclimated steers had decreased temperament score and plasma cortisol compared
      with controls on d 0 (P = 0.02). During feedlot receiving, acclimated steers had
      decreased ADG (P < 0.01) and G:F (P = 0.03) and tended to have decreased DMI (P =
      0.07) compared with controls. Acclimated steers had greater plasma haptoglobin on
      d 4 (P = 0.04) and greater ceruloplasmin from d 0 to 10 (P <= 0.04) and tended to
      have greater cortisol on d 1 (P = 0.08) than controls. In conclusion, temperament
      affects productivity of beef operations based on Bos taurus feeder cattle reared
      in extensive rangeland systems until weaning whereas acclimation to handling
      ameliorated cattle temperament but did not benefit feedlot receiving performance.

PMID- 22952363
TI  - Effects of maternal protein or energy restriction during late gestation on
      antioxidant status of plasma and immune tissues in postnatal goats.
AB  - Maternal malnutrition can have temporary or long-lasting effects on development
      and physiological function of offspring. Our objective was to investigate whether
      maternal protein or energy restriction in late gestation affects the antioxidant
      status of plasma, immune organs (thymus and spleen), and natural barrier organs
      (jejunum) in neonatal goats and whether the effects could be reversed after
      nutritional recovery. Forty-five pregnant goats (Liuyang Blacks) of similar age
      (2.0 +/- 0.3 yr) and BW (22.2 +/- 1.5 kg at d 90 of gestation) were assigned to 3
      dietary treatments during late gestation: control (ME = 9.34 MJ/kg and CP =
      12.5%, DM basis), 40% protein restricted (PR), and 40% energy restricted (ER)
      until parturition, after which offspring received the normal diet for nutritional
      recovery. Plasma and tissues of kids were sampled to determine antioxidant
      enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total
      antioxidant capacity (T-AOC), and catalase (CAT)] and gene expression of
      antioxidant enzymes (Cu/Zn-SOD [SOD1], CAT, and peroxiredoxin 2 [PRDX2]).
      Maternal protein or energy restriction decreased (P < 0.05) SOD activities in
      plasma, liver, thymus, and spleen and SOD1 expression in thymus, and maternal
      energy restriction also decreased (P < 0.05) plasma GSH-Px activity and
      expressions of SOD1 and CAT in liver at birth. After nutritional recovery of 6
      wk, SOD activities in thymus (both in PR and ER) and spleen (only in PR) were
      greater (P < 0.05), but CAT activity of thymus (both in PR and ER) and CAT
      expression (only in ER) were less (P < 0.01) than those in control. After
      nutritional recovery of 22 wk, SOD1 and PRDX2 expression in thymus (both in PR
      and ER) and SOD1 expression in liver (only in ER) were greater (P < 0.05) whereas
      CAT expression in thymus (both in PR and ER) was less (P < 0.001) than in
      control. The current results indicate that maternal protein or energy restriction
      can decrease the antioxidant capacity of the neonatal kids and result in an
      imbalance of SOD and hydrogen peroxide-inactivating systems in thymus, even after
      6 or 22 wk of nutritional recovery.

PMID- 22952364
TI  - Growth-promoting technologies decrease the carbon footprint, ammonia emissions,
      and costs of California beef production systems.
AB  - Increased animal performance is suggested as one of the most effective mitigation
      strategies to decrease greenhouse gas (GHG) and ammonia (NH(3)) emissions from
      livestock production per unit of product produced. Little information exists,
      however, on the effects of increased animal productivity on the net decrease in
      emission from beef production systems. A partial life cycle assessment (LCA) was
      conducted using the Integrated Farm System Model (IFSM) to estimate GHG and NH(3)
      emissions from representative beef production systems in California that use
      various management technologies to enhance animal performance. The IFSM is a farm
      process model that simulates crop growth, feed production, animal performance,
      and manure production and handling through time to predict the performance,
      economics, and environmental impacts of production systems. The simulated beef
      production systems compared were 1) Angus-natural, with no use of growth
      enhancing technologies, 2) Angus-implant, with ionophore and growth-promoting
      implant (e.g., estrogen/trenbolone acetate-based) application, 3) Angus-beta2
      adrenergic agonists (BAA; e.g., zilpaterol), with ionophore, growth-promoting
      implant, and BAA application, 4) Holstein-implant, with growth implant and
      ionophore application, and 5) Holstein-BAA, with ionophore, growth implant, and
      BAA use. During the feedlot phase, use of BAA decreased NH(3) emission by 4 to 9
      g/kg HCW, resulting in a 7% decrease in NH(3) loss from the full production
      system. Combined use of ionophore, growth implant, and BAA treatments decreased
      NH(3) emission from the full production system by 14 g/kg HCW, or 13%. The C
      footprint of beef was decreased by 2.2 kg carbon dioxide equivalent (CO(2)e)/kg
      HCW using all the growth-promoting technologies, and the Holstein beef footprint
      was decreased by 0.5 kg CO(2)e/kg HCW using BAA. Over the full production
      systems, these decreases were relatively small at 9% and 5% for Angus and
      Holstein beef, respectively. The growth-promoting technologies we evaluated are a
      cost-effective way to mitigate GHG and NH(3) emissions, but naturally managed
      cattle can bring a similar net return to Angus cattle treated with growth
      promoting technologies when sold at an 8% greater premium price.

PMID- 22952365
TI  - Nutritional value of dried fermentation biomass, hydrolyzed porcine intestinal
      mucosa products, and fish meal fed to weanling pigs.
AB  - Dried fermentation biomass (DFB) and hydrolyzed porcine intestinal mucosa are co
      products of L-Lys * HCl production and heparin extraction, respectively. Three
      experiments were conducted to determine standardized ileal digestibility (SID) of
      AA (Exp. 1), concentration of DE and ME (Exp. 2), and standardized total tract
      digestibility (STTD) of P (Exp. 3) in DFB and 2 hydrolyzed porcine intestinal
      mucosa products (PEP50 and PEP2+), and compare these values with values for fish
      meal. In Exp. 1, 12 ileal cannulated barrows (BW = 11.5 +/- 1.1 kg) were allotted
      to a replicated 6 * 6 Latin square design with 6 diets and 6 periods. A N-free
      diet, diet based on soybean meal (SBM), and 4 diets based on a combination of SBM
      and DFB, PEP50, PEP2+, or fish meal were formulated. With the exception of Lys,
      there were no differences in SID of indispensable AA between DFB and fish meal.
      Except for Thr, no differences in SID of indispensable AA between PEP50 and fish
      meal were observed, but SID of all indispensable AA, except Lys and Trp, was less
      (P < 0.05) in PEP2+ than in the other ingredients. In Exp. 2, 40 barrows (BW =
      12.8 +/- 1.4 kg) were allotted to 5 diets with 8 pigs/diet. A basal diet
      containing 96.4% corn and 4 diets containing corn and DFB, PEP50, PEP2+, or fish
      meal were formulated. The DE (5,445 kcal/kg DM) and ME (5,236 kcal/kg DM) in DFB
      were greater (P < 0.01) than in PEP50 (4,758 and 4,512 kcal/kg DM for DE and ME,
      respectively) and fish meal (4,227 and 3,960 kcal/kg DM for DE and ME,
      respectively). Also, DE in DFB was greater (P < 0.01) than in PEP2+ (4,935
      kcal/kg DM), but ME in DFB was not different from that in PEP2+ (4,617 kcal/kg
      DM). Furthermore, DE in PEP50 and PEP2+ were greater (P < 0.01) than in fish
      meal, but ME did not differ from that in fish meal. In Exp. 3, 40 barrows (BW =
      12.4 +/- 1.3 kg) were randomly allotted to 5 diets with 8 pigs/diet. A P-free
      diet and 4 diets in which the sole source of P was from DFB, PEP50, PEP2+, or
      fish meal were formulated. The STTD of P in DFB (96.9%) and PEP2+ (97.6%) were
      greater (P < 0.01) than in PEP50 and fish meal (76.2% and 68.5%, respectively),
      and STTD of P in PEP50 was greater (P < 0.01) than in fish meal. In summary, SID
      of most indispensable AA did not differ among DFB, PEP50, and fish meal, but DE
      and ME and STTD of P in DFB were greater than in PEP50 and fish meal.

PMID- 22952366
TI  - Physiological effects of housing density on C57BL/6J mice over a 9-month period.
AB  - The NRC has consistently recommended floor space for animals used in science and
      agriculture. For mice, the recommended floor space is 77.4 cm(2) (12 in(2)) for a
      15- to 25-g mouse. The NRC noted that its recommendations were based on "best
      professional judgment" and encouraged alternatives that were data driven. As part
      of a continual effort of The Jackson Laboratory to ensure the health and well
      being of production and research mice, while promoting cost-effective, state-of
      the-art research, several density-driven studies have been conducted by lab
      researchers. The objectives of this study were to determine the effect of housing
      density on variables related to mouse physiology and air quality in cages and
      assess the value of specific measured variables in such studies. In the present
      study, we monitored C57BL/6J mice in individually ventilated cages from weaning
      until 9 mo of age. Housing densities were equivalent to 66.4 or 36.8 cm(2) per
      mouse (10.3 or 5.7 in(2)). Clinical physiological variables representing general
      health and well-being were measured. Hematological traits, plasma lipids, and
      glucose, growth, bone mineral density, and percent body fat did not differ
      between housing densities. In the more densely housed mice, however, adrenal
      glands were significantly smaller, heart rates were significantly less, and food
      consumption was less. Cage air microenvironment was evaluated for ammonia, carbon
      dioxide, temperature, and humidity in cages changed weekly or every 2 wk. The
      cage microenvironment remained within acceptable limits at the higher density of
      mice at both cage-changing frequencies. The results suggest that mice housed for
      as long as 9 mo at up to twice the density currently recommended by NRC show no
      measurable adverse effects. Continued re-evaluation of the recommendation by
      measuring additional relevant variables of health and general well-being, and
      studying additional strains of mice is warranted.

PMID- 22952367
TI  - Rumen bacterial, archaeal, and fungal diversity of dairy cows in response to
      ingestion of lauric or myristic acid.
AB  - The objective of this experiment, part of a larger study, was to investigate
      changes in rumen bacterial, archaeal, and fungal diversity in cows fed medium
      chain saturated fatty acids. In the main study, 6 lactating dairy cows were dosed
      intraruminally with 240 g/(cow . d) of stearic (SA, control), lauric (LA), or
      myristic (MA) acid in a replicated 3 * 3 Latin square design trial. Experimental
      periods were 28 d, and cows were transfaunated between periods. Lauric acid
      decreased protozoal counts in the rumen by 96% compared with SA and MA (compared
      with SA, MA had no effect on ruminal protozoa). Whole ruminal contents samples
      were collected 2, 4, 6, 8, 10, 14, 18, and 24 h after the morning feeding on d 23
      of each experimental period, stored frozen, and later composited by cow and
      period for microbial profile analyses, which involved tag-encoded flexible (FLX)
      amplicon pyrosequencing to provide diversity analyses of gastrointestinal
      bacterial, archaeal, and fungal populations of the cattle. The LA treatment,
      either directly or through its effect on protozoa, had a profound effect on the
      microbial ecology of the rumen. Ruminal populations of Prevotella, Bacteroides,
      and Enterorhabdus were decreased (P = 0.04 to P < 0.001) by more than 2-fold in
      LA treatments compared with SA, and Clostridium populations were decreased (P =
      0.01) in LA- compared with MA-treated cows. The proportion of Ruminococcus was
      not affected by treatment, although the LA treatment had the least proportion of
      Ruminococcus. Proportions of Eubacterium, Butyrivibrio, Olsenella, and
      Lactobacillus genera were increased (P = 0.03 to 0.01) by LA compared with MA or
      SA. The LA treatment, possibly through its effect on protozoa physically
      associated with archaea, resulted in an increase (P = 0.01) in the archaeal
      methanogenic genus Methanosphaera and a decrease (P = 0.01) in
      Methanobrevibacter. Few changes in fungal populations caused by treatment were
      detected. Collectively, results indicate that LA, either through antiprotozoal or
      direct antimicrobial effects, altered bacterial and archaeal populations in the
      rumen of dairy cows, but effects on fungal populations were not clear.

PMID- 22952368
TI  - Feed restriction applied after weaning has different effects on pig performance
      and health depending on the sanitary conditions.
AB  - Feed restriction may be a strategy used by farmers to limit digestive disorders
      after weaning. The objective of this study was to evaluate the effect of feed
      restriction applied 1 wk after weaning on growth performance and health of pigs
      reared in 2 different sanitary conditions (Good vs. Poor; managed in opposite
      ways with respect to cleaning, animal density, and preventive antibiotic use) and
      confronted with stressful common farming practices (i.e., diet transition and
      building transfer). At weaning at 4 wk of age, 48 pigs were assigned to 1 of the
      4 experimental treatments consisting of 2 sanitary conditions and 2 feeding
      levels (ad libitum vs. restricted). At 2 d after weaning, restricted pigs
      received 20% of the feed quantity consumed by ad libitum pigs. The feeding level
      of the restricted pigs was gradually increased to attain ad libitum feeding on d
      8. Imposed stressful conditions occurred at d 12 (the weaner diet replaced the
      starter diet), d 33 (transfer of pigs from the weaner unit to the grower unit),
      and d 47 (the grower diet replaced the weaner diet). This allowed 4
      distinguishing phases: I, from 0 to 11 d; II, from 12 to 32 d; III, from 33 to 46
      d; and IV, from 47 to 60 d after weaning. Poor sanitary conditions resulted in
      decreased growth performance during phase I (P < 0.001) and III (P < 0.01), and
      the final BW of pigs kept in Poor sanitary conditions was 4 kg less (P = 0.02)
      than those kept in Good sanitary conditions. Plasma haptoglobin concentration was
      increased on d 12 after weaning (P = 0.001) as was the occurrence of soft feces
      during phases II and III (P <= 0.05) in Poor sanitary conditions. In both
      sanitary conditions, the restricted feeding level resulted in decreased ADG (P <
      0.001), increased plasma haptoglobin and salivary cortisol concentrations, and
      feeding-associated behaviors (P < 0.05) during phase I. In Poor sanitary
      conditions, feed restriction was very detrimental and differences in ADFI and ADG
      between restricted and ad libitum pigs increased with time (P = 0.05).
      Conversely, in Good sanitary conditions, restricted pigs attained the BW of ad
      libitum pigs before the end of the experiment. In conclusion, imposing feed
      restriction on pigs during the first days after weaning does not seem to be an
      effective strategy to decrease the negative effects of Poor sanitary conditions;
      rather, it reinforces these effects.

PMID- 22952369
TI  - National Beef Quality Audit-2011: In-plant survey of targeted carcass
      characteristics related to quality, quantity, value, and marketing of fed steers
      and heifers.
AB  - The 2011 National Beef Quality Audit (NBQA-2011) assessed the current status of
      quality and consistency of fed steers and heifers. Beef carcasses (n = 9,802),
      representing approximately 10% of each production lot in 28 beef processing
      facilities, were selected randomly for the survey. Carcass evaluation for the
      cooler assessment of this study revealed the following traits and frequencies:
      sex classes of steer (63.5%), heifer (36.4%), cow (0.1%), and bullock (0.03%);
      dark cutters (3.2%); blood splash (0.3%); yellow fat (0.1%); calloused rib eye
      (0.05%); overall maturities of A (92.8%), B (6.0%), and C or greater (1.2%);
      estimated breed types of native (88.3%), dairy type (9.9%), and Bos indicus
      (1.8%); and country of origin of United States (97.7%), Mexico (1.8%), and Canada
      (0.5%). Certified or marketing program frequencies were age and source verified
      (10.7%), <=A(40) (10.0%), Certified Angus Beef (9.3%), Top Choice (4.1%), natural
      (0.6%), and Non-Hormone-Treated Cattle (0.5%); no organic programs were observed.
      Mean USDA yield grade (YG) traits were USDA YG (2.9), HCW (374.0 kg), adjusted
      fat thickness (1.3 cm), LM area (88.8 cm2), and KPH (2.3%). Frequencies of USDA
      YG distributions were YG 1, 12.4%; YG 2, 41.0%; YG 3, 36.3%; YG 4, 8.6%; and YG
      5, 1.6%. Mean USDA quality grade (QG) traits were USDA quality grade
      (Select(93)), marbling score (Small(40)), overall maturity (A(59)), lean maturity
      (A(54)), and skeletal maturity (A(62)). Frequencies of USDA QG distributions were
      Prime, 2.1%; Choice, 58.9%; Select, 32.6%; and Standard or less, 6.3%. Marbling
      score distribution was Slightly Abundant or greater, 2.3%; Moderate, 5.0%;
      Modest, 17.3%; Small, 39.7%; Slight, 34.6%; and Traces or less, 1.1%. Carcasses
      with QG of Select or greater and YG 3 or less represented 85.1% of the sample.
      This is the fifth benchmark study measuring targeted carcass characteristics, and
      information from this survey will continue to help drive progress in the beef
      industry. Results will be used in extension and educational programs as teaching
      tools to inform beef producers and industry professionals of the current state of
      the U.S. beef industry.

PMID- 22952370
TI  - National Beef Quality Audit-2011: Harvest-floor assessments of targeted
      characteristics that affect quality and value of cattle, carcasses, and
      byproducts.
AB  - The National Beef Quality Audit-2011 (NBQA-2011) was conducted to assess targeted
      characteristics on the harvest floor that affect the quality and value of cattle,
      carcasses, and byproducts. Survey teams evaluated approximately 18,000
      cattle/carcasses between May and November 2011 in 8 beef processing facilities.
      Cattle identification methods were lot visual tags (85.7%), individual visual
      tags (50.6%), electronic tags (20.1%), metal-clip tags (15.7%), other (5.3%),
      none (2.5%), and wattles (0.5%). Hide colors or breed types were black (61.1%),
      red (12.8%), yellow (8.7%), Holstein (5.5%), brown (5.0%), gray (5.0%), white
      (1.4%), and brindle (1.0%). Brand frequencies were none (55.2%), 1 (40.4%), 2
      (4.4%), and 3 or more (0.04%) brands, and brands were located on the butt
      (35.2%), side (9.0%), and shoulder (2.5%). Hide locations of mud or manure were
      no mud/manure (49.2%), legs (36.8%), belly (23.7%), side (14.9%), top-line
      (11.0%), and tail region (13.7%). There were 76.2% of cattle without horns, and
      the majority of those with horns (71.6%) were between 0 cm and 12.7 cm in length.
      Permanent incisor numbers were zero (87.3%), 1 (1.4%), 2 (8.0%), 3 (0.9%), 4
      (1.9%), 5 (0.3%), 6 (0.2%), 7 (0.1%), and 8 (0.02%). Most carcasses (77.0%) were
      not bruised, 18.7% had 1 bruise, 3.4% had 2 bruises, 0.6% had 3 bruises, and 0.3%
      had more than 3 bruises. Bruise locations were loin (50.1%), rib (21.3%), chuck
      (13.8%), round (7.3%), and brisket/flank/plate (7.5%). Condemnation item and
      incidence were whole carcass (none recorded), liver (20.9%), lungs (17.3%),
      tongue (10.0%), viscera (9.3%), and head (7.2%). Compared with the NBQA-2005, the
      NBQA-2011 had an increased percentage of black-hided cattle (56.3 vs. 61.1%),
      more cattle with brands (38.7 vs. 44.8%), and more cattle with some form of
      identification (93.3 vs. 97.5%). In addition, there was a lesser percentage of
      carcasses with bruising in 2011 (23.0%) than in 2005 (35.2%), as well as a
      smaller percentage of carcasses with more than 1 bruise (2005 = 9.4% vs. 2011 =
      4.2%). Compared with the 2005 audit, a similar percentage of the cattle were
      deemed 30 mo of age or older using dentition (2005 = 2.7% vs. 2011 = 3.3%). The
      information from NBQA-2011 helps the beef industry measure progress against
      previous NBQA assessments and provides a benchmark for future educational and
      research activities.

PMID- 22952371
TI  - Genetic parameters for carnitine, creatine, creatinine, carnosine, and anserine
      concentration in longissimus muscle and their association with palatability
      traits in Angus cattle.
AB  - The objective of this study was to estimate genetic parameters for carnitine,
      creatine, creatinine, carnosine, and anserine concentration in LM and to evaluate
      their associations with Warner-Bratzler shear force (WBSF) and beef palatability
      traits. Longissimus muscle samples from 2,285 Angus cattle were obtained and
      fabricated into steaks for analysis of carnitine, creatine, creatinine,
      carnosine, anserine, and other nutrients, and for trained sensory panel and WBSF
      assessments. Restricted maximum likelihood procedures were used to obtain
      estimates of variance and covariance components under a multiple-trait animal
      model. Estimates of heritability for carnitine, creatine, creatinine, carnosine,
      and anserine concentrations in LM from Angus cattle were 0.015, 0.434, 0.070,
      0.383, and 0.531, respectively. Creatine, carnosine, and anserine were found to
      be moderately heritable, whereas almost no genetic variation was observed in
      carnitine and creatinine. Moderate positive genetic (0.25, P < 0.05) and
      phenotypic correlations (0.25, P < 0.05) were identified between carnosine and
      anserine. Medium negative genetic correlations were identified between creatine
      and both carnosine (-0.53, P < 0.05) and anserine (-0.46, P < 0.05). Beef and
      livery/metallic flavor were not associated with any of the 5 compounds analyzed
      (P > 0.10), and carnitine concentrations were not associated (P > 0.10) with any
      of the meat palatability traits analyzed. Carnosine was negatively associated
      with overall tenderness as assessed by trained sensory panelists. Similar
      negative associations with overall tenderness were identified for creatinine and
      anserine. Painty/fishy was the only flavor significantly and negatively
      associated with creatinine and carnosine. These results provide information
      regarding the concentration of these compounds, the amount of genetic variation,
      and evidence for negligible associations with beef palatability traits in LM of
      beef cattle.

PMID- 22952372
TI  - Modification of activities of the ruminal ecosystem and its bacterial and
      protozoan composition during repeated dietary changes in cows.
AB  - Dietary change alters the ruminal ecosystem and can be regarded as a disturbance.
      Studying the response to a disturbance can help us understand the behavior of the
      ecosystem. Our work is concerned with the response of the ruminal ecosystem
      (composition and activities) during the application of repeated dietary
      disturbances to 6 dry Holstein cows. For 2 mo, the cows received a hay-based diet
      [experimental period (EP) 0], followed by 3 EP of successive changes (EP 1, 2,
      and 3) comprised of 2 parts: the first (10 d) with a corn silage-based diet and
      the second (25 d) with a hay-based diet. The measurements and samplings were done
      on the last days of EP 0 and of each part of EP 1 through 3, with the results of
      EP 0 used as covariables in the statistical models. The physicochemical
      measurements (pH and redox potential) and the fermentation variables (VFA,
      ammonia) were determined hourly between the morning and evening meals (n = 8
      measurements/d). Samples of ruminal contents were taken 3 h after the morning
      meal to determine enzymatic activity [amylase, carboxymethyl cellulase (CMCase),
      and xylanase], to count the main protozoan genera and to quantify the bacteria by
      quantitative PCR, and to determine its structure by the capillary electrophoresis
      single-strand conformation polymorphism process. The pH fell for the corn silage
      based diet with the EP (P < 0.05) but not for the hay-based diet. The VFA
      concentration decreased for both diets with the EP (P < 0.001), with the primary
      changes in acetate and propionate. The ammonia concentration increased for the
      corn silage-based diet with the EP (P < 0.05), whereas for the hay-based diet the
      highest value was observed for EP 2 (P < 0.05). The total quantity of bacteria
      decreased between EP 1 and 3 (P < 0.05) for both diets. The structure of the
      bacterial community was not affected by the disturbances for the corn silage
      based diet, whereas for the hay-based diet large differences were evident between
      EP 1 and 3 (P < 0.05) and 2 and 3 (P < 0.01). The number of protozoa increased
      over the EP, with a more marked effect for the corn silage-based diet (diet * EP
      interaction, P < 0.05). The specific amylase, CMCase, and xylanase activities
      decreased over the EP for both diets (P < 0.05). The dietary changes applied in
      our experiment involved strong modifications of the ruminal ecosystem and
      alterations of ruminal fermentation and enzymatic activities. These alterations
      were reinforced with the repetition of the dietary changes.

PMID- 22952373
TI  - Effects of corn distillers dried grains with solubles on quality traits of pork.
AB  - The high cost of feed grains has led swine producers to seek alternative
      feedstuffs, such as distillers dried grains with solubles (DDGS). However, little
      is known about the effects of high levels of DDGS in swine diets on pork quality.
      The objective of this study was to evaluate belly processing and bacon, sausage,
      and loin quality of pigs fed high levels of DDGS. Sixty pigs averaging 34 kg BW
      were fed fortifi ed corn-soybean meal diets containing 0%, 15%, 30%, or 45% DDGS.
      At 120 kg BW, the pigs were humanely harvested and bellies, loins, and shoulders
      were removed from the left side of each carcass. Flex tests of bellies indicated
      that they became softer (linear, P < 0.03) as DDGS levels increased. The PUFA in
      backfat and belly fat increased linearly (P < 0.005), as did iodine values with
      increasing 0DDGS in the diet. Bellies were pumped to target 12% brine retention,
      cooked, and sliced at a commercial facility. Slicing yield was not affected by
      DDGS level fed. Fresh bacon slices were scored 1 to 6 with 1 representing no
      visible cracks in the fat and 6 representing a spider weblike shattering of the
      fat. Shatter scores decreased (linear, P < 0.001) with increasing dietary DDGS.
      Bratwurststyle sausage was produced by combining ground Boston butts and picnics
      to target 30% fat, blended with commercial seasonings, and stuffed into natural
      casings. Loose sausage was placed on trays, overwrapped with polyvinyl chloride
      wrap, and stored under constant, cool white fl orescent lighting (1,300 lx) at 4
      degrees C. Objective color values (L*, a*, and b*) were taken on loosepackaged
      sausage mix at 6 locations at the same time daily for 7 d. Sausage was also
      sampled for thiobarbituric acid reactive substances (TBARS) at the same time
      daily on d 0, 3, 5, and 7. Color scores of sausage were not consistently affected
      by DDGS level in the diet and the changes were slight. The TBARS in sausage from
      pigs fed the 30% and 45% DDGS diets increased to a greater extent from d 0 to 7
      than in those fed the control or 15% DDGS diets. An 8-member, trained panel
      evaluated the sensory attributes of bacon slices, sausage, and loin chops. The
      DDGS resulted in a softer texture (P < 0.004) and increased juiciness (P < 0.04)
      in sausages, but no differences in sensory scores were found in bacon slices or
      loin chops. The results indicate that the softer bellies, greater concentrations
      of PUFA in carcass fat, and greater iodine values associated with feeding
      increased DDGS did not negatively affect slicing yield of cured bellies, quality
      of fresh bacon slices, or eating quality of bacon, sausage, or loin chops.

PMID- 22952374
TI  - Fresh meat quality and further processing characteristics of shoulders from
      finishing pigs fed ractopamine hydrochloride (Paylean).
AB  - Our objectives were to characterize the effects of ractopamine hydrochloride
      (RAC) on fresh meat and further processing characteristics of muscles (serratus
      ventralis and triceps brachii) from the shoulders of finishing pigs. Two hundred
      forty shoulders originating from 120 carcasses (60 barrows and 60 gilts) were
      selected from a commercial population of pigs. A 2 * 2 factorial in a completely
      randomized design was used, with factors of RAC inclusion in the diet (0 or 7.4
      mg/kg, as-fed basis) and sex (barrow or gilt). Paired shoulders (120 rights and
      120 lefts) were transported from a federally inspected slaughter facility under
      refrigeration to the University of Illinois Meat Science Laboratory for
      evaluation. Subsequently, right and left shoulders were separated and designated
      for 2 separate experiments. Shoulders from right side were used in Exp. 1 to
      determine further processing characteristics. Cellar trimmed (CT) butts from the
      Boston butt of the shoulders were cured and dried-cured to manufacture cottage
      bacon and coppa, respectively. Shoulders from left side were used in Exp. 2 to
      determine fresh meat characteristics. Pigs fed RAC had greater shoulder weights
      and increased yields of cuts from the shoulder. Feeding RAC decreased Boston butt
      fat content (P = 0.01) but had no effect on picnic fat content (P = 0.86). Pigs
      fed RAC had greater (P < 0.01) iodine values than controls (67.00 vs. 64.95,
      respectively). Inclusion of RAC in the diet had no effect on cottage bacon cooked
      yield (P = 0.33), but it decreased (P < 0.01) cottage bacon fat content without
      having an effect on protein content (P = 0.50). In addition, cottage bacon from
      RAC shoulders had greater slice total area (P = 0.01) and less seam fat (P =
      0.01) than controls. Ractopamine hydrochloride had no detrimental effect on coppa
      processing characteristics and visual appearance. Cottage bacon and coppa from
      RAC pigs had sensory characteristics similar to controls. Shoulders from pigs fed
      RAC might be of benefit to the industry because they provide more pounds of
      sellable product with no detrimental effects on processing characteristics.

PMID- 22952375
TI  - Prepartum dietary energy source fed to beef cows: II. Effects on progeny
      postnatal growth, glucose tolerance, and carcass composition.
AB  - Mature Angus-cross beef cows (n = 228) were used to evaluate effects of prepartum
      dietary energy source on postnatal growth and carcass composition of progeny in a
      2-yr study. Starting at approximately 160 d of gestation, cows were fed diets
      consisting of 1 of 3 primary energy sources: grass hay (HY), corn (CN), or dried
      corn distillers grains with solubles (DG). The CN and DG diets were limit-fed to
      achieve similar energy intakes as cows fed HY. Following parturition, cows were
      fed a common diet and managed as a single group. Calves were weaned at an average
      of 185 +/- 6 d of age and backgrounded for 28 d. A subset of progeny (n = 134)
      was individually fed a common finishing diet until slaughter, when each calf
      reached 1.2 +/- 0.05 cm of backfat. A glucose tolerance test (GTT) was conducted
      in year 2 on 4 calves/treatment after 41 and 111 d on the finishing diet (DOF).
      Calf birth weights were greater (P = 0.002) in calves from cows fed CN and DG
      than calves from cows fed HY, and weaning BW (P = 0.08) was less for calves from
      cows fed HY vs. CN. Receiving BW, final BW, and HCW did not differ (P >= 0.16)
      among treatments. No difference (P >= 0.28) in ADG, morbidity, and mortality from
      birth to slaughter was observed among treatments. In response to a GTT, increased
      DOF resulted in greater (P <= 0.005) fasting insulin, faster glucose
      disappearance rate, and greater insulin:glucose area under the curve ratio.
      Glucose disappearance rate was greater (P = 0.01) in calves from cows fed CN than
      in calves from cows fed HY or DG. A greater initial insulin response (P = 0.005)
      was observed in calves from cows fed CN or DG than in calves from cows fed HY.
      Carcass traits used to measure yield grade did not differ (P >= 0.19) among
      treatments. Calves from dams fed CN had the lowest marbling score (P = 0.03) and
      intramuscular fat content (P = 0.07). These results indicate that prepartum
      maternal dietary energy source can alter fetal adipose tissue development and
      insulin sensitivity resulting in long-term effects on progeny's intramuscular fat
      deposition. Moreover, present findings suggest that increasing the number of days
      on a corn-based finishing diet increases insulin resistance in beef cattle.

PMID- 22952376
TI  - Effects of two feeder designs and adjustment strategies on the growth performance
      and carcass characteristics of growing-finishing pigs.
AB  - Our objective was to compare effects of a conventional dry (CD, 152.4-cm-wide, 5
      space, Staco Inc., Schaefferstown, PA) and a wet-dry (WD, double-sided, each side
      = 38.1-cm-space, Crystal Springs, GroMaster Inc., Omaha, NE) feeder using various
      feeder adjustment openings on the growth performance and carcass characteristics
      of growing-finishing pigs (Sus scrofa). In Exp. 1, 1,296 pigs (BW 19 kg) were
      used in a 27-d study to evaluate 3 feeder openings nested within each feeder
      design. From d 0 to 27, pigs fed with a WD feeder had similar ADG, but lower (P <
      0.02) ADFI and greater G:F than pigs fed with a CD feeder. Increased adjustment
      opening increased (linear, P < 0.01) ADG and ADFI by pigs fed with a WD feeder,
      and increased (linear, P < 0.01) ADFI by pigs fed with a CD feeder. In Exp. 2,
      1,248 pigs (BW 33 kg) were used to evaluate 3 feeder openings nested within each
      feeder design in a 93-d study. Pigs fed with a WD feeder had greater (P < 0.05)
      ADG, ADFI, final BW, HCW, and backfat, but decreased fat-free lean index (FFLI)
      than those fed with a CD feeder. Increased opening of the WD feeder resulted in
      greater (linear, P < 0.05) ADG, ADFI, HCW, and backfat, but lower FFLI. No
      differences among CD feeder openings were observed, and G:F did not differ among
      all feeder treatments. In Exp. 3, 1,287 pigs (BW 38 kg) were used in a 92-d
      factorial experiment with 4 feeder treatments and 2 diet types (low and high
      byproduct diets). Feeder treatments were CD at approximately a 2.4-cm opening, WD
      at a 3.2-cm opening, WD changed to a 2.5-cm opening on d 56, and WD changed to a
      2.5-cm opening on d 28 and a 1.9-cm opening on d 56. Pigs fed with a WD feeder
      had greater (P < 0.01) ADG, ADFI, HCW, and backfat, but decreased FFLI than pigs
      fed with a CD feeder. Decreasing the WD feeder opening during the study decreased
      (P < 0.05) ADG. Pigs with the WD feeder opening decreased to 1.9 cm had reduced
      (P < 0.05) ADFI and backfat, but increased FFLI compared with pigs with a WD
      feeder opening of 3.2 cm. Feed efficiency did not differ among treatments. In
      conclusion, ADG, ADFI, HCW, and backfat were increased with the WD feeder
      evaluated in this experiment, but the growth of pigs fed with a WD feeder was
      more sensitive to differences in feeder adjustment than that of pigs fed with a
      CD feeder.

PMID- 22952377
TI  - Genetic associations between behavioral traits and direct-social effects of
      growth rate in pigs.
AB  - This study examined the behavioral consequences of selecting pigs using a social
      genetic model for growth. Calculations enable each member of a group of pigs to
      be given a direct breeding value (DBV) and a social breeding value (SBV), which
      can be summarized into a total breeding value (TBV) for growth. Selection for
      growth TBV could affect animal behavior because social effects account for within
      group interactions. Data were recorded from 96 groups of Yorkshire and Yorkshire
      * Landrace pigs in a nucleus herd. Each group contained 15 pigs fed ad libitum
      from 2 feeders; the space allowance was 0.85 m2/pig. Average daily gain was
      quantified from 35 to 100 kg of BW. Fighting and bullying activity at mixing
      (period 1), lying frequency 3 wk after mixing (period 2), and counts of skin
      lesions in periods 1 and 2 were recorded. The DBV for these traits were estimated
      with a classic animal model. We simulated different correlations between the
      direct genetic effect and the social genetic effect on growth rate (r(DS)), 2
      components that respectively determine a pig's genetic capacity to grow and its
      genetic influence on growth of group mates: r(DS) was successively assumed to be
      0 and +/-0.12, +/-0.20, +/-0.29, and +/-0.58. Finally, the correlations between
      DBV, SBV, and TBV for ADG, as well as the DBV for behavior and skin lesions, were
      calculated and tested for a level of significance at P < 0.05. The gradient from
      negative to positive values of r(DS) refers to a progressive path running from
      genetic antagonism to genetic mutualism for growth. If rDS in the population
      truly ranged between -0.58 and -0.20, correlations for TBV for ADG with DBV for
      fighting and bullying progressively increased with rDS. Consequently, if rDS was
      low (between -0.12 and +0.12) or positive (>+0.12), pigs with high TBV for ADG
      had higher DBV for bullying other pigs in the group and for fighting than pigs
      with lower TBV for ADG. Pigs with high TBV for ADG did not differ from other pigs
      in their DBV for lesions to the anterior part of the body, but they had a lower
      DBV for posterior lesions, whereas in period 2, they had higher DBV for posterior
      lesions and lower DBV for lying. Under genetic mutualism for growth and in
      housing conditions similar to those in the present study, selection for growth
      TBV would promote the rapid establishment of the dominance relationships, with
      more aggressive contests among group mates at mixing. Pigs would subsequently be
      more active but, judging by skin lesions, less willing to fight in a more stable
      social situation.

PMID- 22952378
TI  - Seed dormancy distribution: explanatory ecological factors.
AB  - BACKGROUND AND AIMS: Knowledge of those traits that vary with latitude should be
      helpful in predicting how they may evolve locally under climate change. In the
      sea beet Beta vulgaris ssp. maritima, seed dormancy largely controls the timing
      of germination, is highly heritable and varies geographically; it is therefore
      thought to be selected by climate. The aim here was to characterize the variation
      in seed dormancy among sea beet populations across the French distribution area,
      as well as the ecological factors in situ that are correlated with and that could
      therefore select for seed dormancy. The relative importance of genetic
      inheritance vs. non-genetic variation is also evaluated. METHODS: The proportions
      of dormant seeds from 85 natural populations encompassing different climates over
      the whole French distribution area were measured under controlled conditions.
      Germination phenology was observed in a common garden experiment. Dormancy
      variation of seeds collected in situ was compared with that of seeds collected on
      plants grown in the greenhouse. KEY RESULTS: The proportions of dormant seeds in
      the greenhouse were highly variable, covering almost the entire range from 0 to
      1, and followed a geographical pattern from lower dormancy at high latitudes to
      high dormancy at low latitudes. The distribution of dormancy was positively
      correlated with yearly temperatures, especially summer temperatures. Minimum
      temperatures in winter did not significantly explain the trait variation. The
      genetic component of the total variation was significant and is probably
      completed by an important adjustment to the local conditions brought about by
      maternal adaptive phenotypic plasticity. CONCLUSIONS: Dormancy in sea beet could
      be interpreted as a way to limit summer germination and spread germination over
      the first autumn and spring or following autumns. This highly heritable trait has
      the potential to evolve in the relatively near future because of climate change.

PMID- 22952379
TI  - Pathologic outcomes of nonmalignant papillary breast lesions diagnosed at imaging
      guided core needle biopsy.
AB  - PURPOSE: To determine the upstage rate from nonmalignant papillary breast lesions
      obtained at imaging-guided core needle biopsy (CNB) and if there are any
      clinical, imaging, or pathologic features that can be used to predict eventual
      upstaging to malignancy. MATERIALS AND METHODS: This retrospective case review
      was institutional review board approved and HIPAA compliant, with a waiver of
      informed consent. A database search (from January 2001 to March 2010) was
      performed to find patients with a nonmalignant papillary breast lesion diagnosed
      at CNB. Of the resulting 128 patients, 86 (67%) underwent surgical excision; 42
      (33%) patients were observed with imaging, for a median observation time of 4.1
      years (range, 1.0-8.6 years). Chart review was performed to determine pertinent
      features of each case. RESULTS: Fourteen of 128 patients were subsequently found
      to have malignancy at excision, for an upstage rate of 11%. Nine (7%) of the 128
      patients were subsequently found to have atypia at excision. Comparisons between
      patients with upstaged lesions and patients whose lesions were not upstaged
      demonstrated patients with upstaged lesions to be slightly older (65 vs 56 years,
      P=.01), more likely to have a mass than calcifications at imaging (P=.03), and to
      have had less tissue obtained at biopsy (three vs five cores obtained, P=.02; 14-
      vs 9-gauge needle used, P<.01; no vacuum assistance used, P<.01). Most strongly
      predictive of eventual malignancy, however, was whether the interpreting
      pathologist qualified the benign diagnosis at CNB with additional commentary
      (P<.01). CONCLUSION: Given the substantial upstage rate (11%) of papillary
      lesions diagnosed at imaging-guided CNB, surgical excision is an appropriate
      management decision; however, careful evaluation in concert with an expert breast
      pathologist may allow for observation in appropriately selected patients.

PMID- 22952380
TI  - Lumbosacral transitional vertebrae: association with low back pain.
AB  - PURPOSE: To assess the prevalence and degree of lumbosacral transitional
      vertebrae (LSTV) in the Osteoarthritis Initiative (OAI) cohort, to assess whether
      LSTV correlates with low back pain (LBP) and buttock pain, and to assess the
      reproducibility of grading LSTV. MATERIALS & METHODS: Institutional review board
      approval was obtained, and informed consent documentation was approved for the
      study protocol. Standard standing pelvic radiographs that included the transverse
      processes of L5 were graded according to Castellvi classification of LSTV in 4636
      participants (1992 men and 2804 women; aged 45-80 years) from the OAI cohort.
      These data were correlated with prevalence and severity of LBP and buttock pain.
      RESULTS: Prevalence of LSTV was 18.1% (841 of 4636), with a higher rate in men
      than in women (28.1% vs 11.1%, respectively; P<.001). Of the 841 individuals with
      LSTV, 41.72% were type I (dysplastic enlarged transverse process), 41.4% were
      type II (pseudoarticulation), 11.5% were type III (fusion), and 5.2% were type IV
      (one transverse process fused and one with pseudoarticulation). Of the
      participants without LSTV, 53.9% reported LBP, while the prevalence of LBP for
      types I, II, III, and IV was 46%, 73%, 40%, and 66%, respectively (P<.05, chi2
      test). Types II and IV had higher prevalence and severity of LBP and buttock pain
      (P<.001). CONCLUSION: LSTV types II and IV positively correlate with prevalence
      and severity of LBP and buttock pain.

PMID- 22952381
TI  - Automated extraction of critical test values and communications from unstructured
      radiology reports: an analysis of 9.3 million reports from 1990 to 2011.
AB  - PURPOSE: To determine the frequency of critical radiology results in 9.3 million
      radiology reports from our health system, to identify those containing
      documentation of communication by using automated text-classification algorithms,
      and to assess the impact of a policy requiring documentation of critical results
      communication. MATERIALS AND METHODS: This HIPAA-compliant retrospective study
      received institutional review board approval. Text-mining algorithms that were
      previously validated to have mean accuracies of more than 90% for identifying
      certain critical results and documentation of communications were applied to a
      database of 9.3 million radiology reports. The frequency of critical results and
      documentation of communication were then determined from 1990 to 2011. RESULTS:
      There was an increase in documentation of communication for all critical results
      from 1990 to 2011. In 1990, 19.0% of reports with critical values had evidence of
      documentation of communication compared with 72.4% of reports in 2010. The linear
      trend for increasing documentation of communications began in 1997 and continued
      until 2011 (P < .001). From 1990 to 2011, documentation of communication was
      highest in acute scrotal torsion (70.6%) and ectopic pregnancy (65.4%) and lowest
      in unexplained free-intraperitoneal air (29.5%) and malpositioned tubes (30.4%).
      In 2010-2011, radiologists were least likely to document communication of results
      for malpositioned endotracheal and enteric tubes (2010, 58.56%; 2011, 57.50%) and
      unexplained free-intraperitoneal air (2010, 59.57%; 2011, 75.51%). They were most
      likely to document communication of results for ectopic pregnancy (2010, 94.12%;
      2011, 93.48%) and acute appendicitis (2010, 86.87%; 2011, 84.31%). CONCLUSION:
      There was an increase in documentation of communication of critical results,
      which demonstrated a rising linear trend that began in 1997 and continued until
      2011. The increasing trend began well before policy implementation, indicating
      that other factors such as heightened awareness among radiologists likely had a
      role.

PMID- 22952382
TI  - Performance characteristics of MR imaging in the evaluation of clinically low
      risk prostate cancer: a prospective study.
AB  - PURPOSE: To prospectively evaluate diagnostic performance of T2-weighted magnetic
      resonance (MR) imaging and MR spectroscopic imaging in detecting lesions
      stratified by pathologic volume and Gleason score in men with clinically
      determined low-risk prostate cancer. MATERIALS AND METHODS: The institutional
      review board approved this prospective, HIPAA-compliant study. Written informed
      consent was obtained from 183 men with clinically low-risk prostate cancer (cT1
      cT2a, Gleason score<=6 at biopsy, prostate-specific antigen [PSA] level<10 ng/mL
      [10 MUg/L]) undergoing MR imaging before prostatectomy. By using a scale of 1-5
      (score 1, definitely no tumor; score 5, definitely tumor), two radiologists
      independently scored likelihood of tumor per sextant on T2-weighted images. Two
      spectroscopists jointly recorded locations of lesions with metabolic features
      consistent with tumor on MR spectroscopic images. Whole-mount step-section
      histopathologic analysis constituted the reference standard. Diagnostic
      performance at sextant level (T2-weighted imaging) and detection sensitivities
      (T2-weighted imaging and MR spectroscopic imaging) for lesions of 0.5 cm3 or
      larger were calculated. RESULTS: For T2-weighted imaging, areas under the
      receiver operating characteristic curves for sextant-level detection were 0.77
      (reader 1) and 0.82 (reader 2). For lesions of >=0.5 cm3 and, 1<cm3,
      sensitivities were significantly lower when the lesion Gleason score was <=6
      (0.44 [reader 1] and 0.61 [reader 2]) rather than when the Gleason score was >=7
      (0.73, P=.02 [reader 1]; and 0.84, P=.05 [reader 2]). For lesions of >=1 cm3,
      lesion Gleason score did not significantly affect sensitivity (0.83 [reader 1]
      and 1.00 [reader 2] for Gleason score<=6 vs 0.82 and 0.92 for Gleason score>=7;
      P>=.07). MR spectroscopic imaging sensitivity was low and was not significantly
      affected by pathologic lesion volume or Gleason score. CONCLUSION: In men with
      clinically low-risk prostate cancer, detection of lesions of <1 cm3 with T2
      weighted imaging is significantly dependent on lesion Gleason score; detection of
      lesions of >=1 cm3 is significantly better than detection of smaller lesions and
      is not affected by lesion Gleason score. The role of MR spectroscopic imaging
      alone in this population is limited.

PMID- 22952383
TI  - Hyperpolarized 3He and 129Xe MR imaging in healthy volunteers and patients with
      chronic obstructive pulmonary disease.
AB  - PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129
      (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy
      volunteers and patients with chronic obstructive pulmonary disease (COPD) and to
      evaluate the correlations between 3He and 129Xe MR imaging measurements and those
      from spirometry and plethysmography. MATERIALS AND METHODS: This study was
      approved by an ethics board and compliant with HIPAA. Written informed consent
      was obtained from all subjects. Eight healthy volunteers and 10 patients with
      COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect
      percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated
      segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He
      (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at
      hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon
      signed rank test and analysis of variance; Pearson correlation coefficients were
      used to evaluate the relationships among measurements. RESULTS: 129Xe VDP was
      significantly greater than 3He VDP for patients with COPD (P<.0001) but not for
      healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant
      correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1
      second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84,
      P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the
      FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was
      significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84,
      P<.0001). A significant correlation was also observed for 3He and 129Xe ADC
      (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity
      of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema
      measurements (areas with attenuation values in the 15th percentile: r=-0.91,
      P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87,
      P=.001). CONCLUSION: In patients with COPD, the VDP obtained with hyperpolarized
      29Xe MR imaging was significantly greater than that with 3He MR imaging,
      suggesting incomplete or delayed filling of lung regions that may be related to
      the different properties of 129Xe gas and physiologic and/or anatomic
      abnormalities in COPD.

PMID- 22952384
TI  - Screening of illegal intracorporeal containers ("body packing"): is abdominal
      radiography sufficiently accurate? A comparative study with low-dose CT.
AB  - PURPOSE: To evaluate the diagnostic performance of abdominal radiography in the
      detection of illegal intracorporeal containers (hereafter, packets), with low
      dose computed tomography (CT) as the reference standard. MATERIALS AND METHODS:
      This study was approved by the institutional ethical review board, with written
      informed consent. From July 2007 to July 2010, 330 people (296 men, 34 women;
      mean age, 32 years [range, 18-55 years]) suspected of having ingested drug
      packets underwent supine abdominal radiography and low-dose CT. The presence or
      absence of packets at abdominal radiography was reported, with low-dose CT as the
      reference standard. The density and number of packets (<= 12 or >12) at low-dose
      CT were recorded and analyzed to determine whether those variables influence
      interpretation of results at abdominal radiography. RESULTS: Packets were
      detected at low-dose CT in 53 (16%) suspects. Sensitivity of abdominal
      radiography for depiction of packets was 0.77 (41 of 53), and specificity was
      0.96 (267 of 277). The packets appeared isoattenuated to the bowel contents at
      low-dose CT in 16 (30%) of the 53 suspects with positive results. Nineteen (36%)
      of the 53 suspects with positive low-dose CT results had fewer than 12 packets.
      Packets that were isoattenuated at low-dose CT and a low number of packets (<=12)
      were both significantly associated with false-negative results at abdominal
      radiography (P = .004 and P = .016, respectively). CONCLUSION: Abdominal
      radiography is mainly limited by low sensitivity when compared with low-dose CT
      in the screening of people suspected of carrying drug packets. Low-dose CT is an
      effective imaging alternative to abdominal radiography.

PMID- 22952385
TI  - Workplace measurements by the US Occupational Safety and Health Administration
      since 1979: descriptive analysis and potential uses for exposure assessment.
AB  - BACKGROUND: Inspectors from the US Occupational Safety and Health Administration
      (OSHA) have been collecting industrial hygiene samples since 1972 to verify
      compliance with Permissible Exposure Limits. Starting in 1979, these measurements
      were computerized into the Integrated Management Information System (IMIS). In
      2010, a dataset of over 1 million personal sample results analysed at OSHA's
      central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only
      partially overlapping the IMIS database, was placed into public domain via the
      internet. We undertook this study to inform potential users about the
      relationship between this newly available OSHA data and IMIS and to offer insight
      about the opportunities and challenges associated with the use of OSHA
      measurement data for occupational exposure assessment. METHODS: We conducted a
      literature review of previous uses of IMIS in occupational health research and
      performed a descriptive analysis of the data recently made available and compared
      them to the IMIS database for lead, the most frequently sampled agent. RESULTS:
      The literature review yielded 29 studies reporting use of IMIS data, but none
      using the CEHD data. Most studies focused on a single contaminant, with silica
      and lead being most frequently analysed. Sixteen studies addressed potential bias
      in IMIS, mostly by examining the association between exposure levels and
      ancillary information. Although no biases of appreciable magnitude were
      consistently reported across studies and agents, these assessments may have been
      obscured by selective under-reporting of non-detectable measurements. The CEHD
      data comprised 1 450 836 records from 1984 to 2009, not counting analytical
      blanks and erroneous records. Seventy eight agents with >1000 personal samples
      yielded 1 037 367 records. Unlike IMIS, which contain administrative information
      (company size, job description), ancillary information in the CEHD data is mostly
      analytical. When the IMIS and CEHD measurements of lead were merged, 23 033
      (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%)
      records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD
      database. While IMIS-only records represent data analysed in other laboratories,
      CEHD-only records suggest partial reporting of sampling results by OSHA
      inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only
      data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only
      datasets, respectively, suggesting differential under-reporting of non-detects in
      IMIS. CONCLUSIONS: IMIS and the CEHD datasets represent the biggest source of
      multi-industry exposure data in the USA and should be considered as a valuable
      source of information for occupational exposure assessment. The lack of empirical
      data on biases, adequate interpretation of non-detects in OSHA data, complicated
      by suspected differential under-reporting, remain the principal challenges to the
      valid estimation of average exposure conditions. We advocate additional
      comparisons between IMIS and CEHD data and discuss analytical strategies that may
      play a key role in meeting these challenges.

PMID- 22952386
TI  - Radiological assessment for bauxite mining and alumina refining.
AB  - OBJECTIVE: Two international benchmarks assess whether the mining and processing
      of ores containing Naturally Occurring Radioactive Material (NORM) require
      management under radiological regulations set by local jurisdictions. First, the
      1 Bq/g benchmark for radionuclide head of chain activity concentration determines
      whether materials may be excluded from radiological regulation. Second, processes
      may be exempted from radiological regulation where occupational above-background
      exposures for members of the workforce do not exceed 1 mSv/year. This is also the
      upper-limit of exposure prescribed for members of the public. Alcoa of Australia
      Limited (Alcoa) has undertaken radiological evaluations of the mining and
      processing of bauxite from the Darling Range of Western Australia since the
      1980s. Short-term monitoring projects have demonstrated that above-background
      exposures for workers do not exceed 1 mSv/year. A whole-of-year evaluation of
      above-background, occupational radiological doses for bauxite mining, alumina
      refining and residue operations was conducted during 2008/2009 as part of the
      Alcoa NORM Quality Assurance System (NQAS). The NQAS has been guided by
      publications from the International Commission on Radiological Protection (ICRP),
      the International Atomic Energy Agency (IAEA) and the Australian Radiation
      Protection and Nuclear Safety Agency (ARPANSA). The NQAS has been developed
      specifically in response to implementation of the Australian National Directory
      on Radiation Protection (NDRP). METHODS: Positional monitoring was undertaken to
      increase the accuracy of natural background levels required for correction of
      occupational exposures. This is important in view of the small increments in
      exposure that occur in bauxite mining, alumina refining and residue operations
      relative to natural background. Positional monitoring was also undertaken to
      assess the potential for exposure in operating locations. Personal monitoring was
      undertaken to characterise exposures in Similar Exposure Groups (SEGs). The
      monitoring was undertaken over 12 months, to provide annual average assessments
      of above-background doses, thereby reducing temporal variations, especially for
      radon exposures. The monitoring program concentrated on gamma and radon
      exposures, rather than gross alpha exposures, as past studies have shown that
      gross alpha exposures from inhalable dust for most of the workforce are small in
      comparison to combined gamma and radon exposures. RESULTS: The natural background
      determinations were consistent with data in the literature for localities near
      Alcoa's mining, refining and residue operations in Western Australia, and also
      with UNSCEAR global data. Within the mining operations, there was further
      consistency between the above-background dose estimates and the local
      geochemistry, with slight elevation of dose levels in mining pits. Conservative
      estimates of above-background levels for the workforce have been made using an
      assumption of 100% occupancy (1920 hours per year) for the SEGs considered. Total
      incremental composite doses for individuals were clearly less than 1.0 mSv/year
      when gamma, radon progeny and gross alpha exposures were considered. This is
      despite the activity concentration of some materials being slightly higher than
      the benchmark of 1 Bq/g. CONCLUSIONS: The results are consistent with previous
      monitoring and demonstrate compliance with the 1 mSv/year exemption level within
      mining, refining and residue operations. These results will be of value to
      bauxite mines and alumina refineries elsewhere in the world.

PMID- 22952387
TI  - Assessment of hand-transmitted vibration exposure from motorized forks used for
      beach-cleaning operations.
AB  - Motorized vibrating manure forks were used in beach-cleaning operations following
      the massive Deepwater Horizon oil spill in the Gulf of Mexico during the summer
      of 2010. OBJECTIVES: The objectives of this study were to characterize the
      vibration emissions of these motorized forks and to provide a first approximation
      of hand-transmitted vibration exposures to workers using these forks for beach
      cleaning. METHODS: Eight operators were recruited to operate the motorized forks
      during this laboratory study. Four fork configurations were used in the study;
      two motor speeds and two fork basket options were evaluated. Accelerations were
      measured near each hand as the operators completed the simulated beach-cleaning
      task. RESULTS: The dominant vibration frequency for these tools was identified to
      be around 20 Hz. Because acceleration was found to increase with motor speed,
      workers should consider operating these tools with just enough speed to get the
      job done. These forks exhibited considerable acceleration magnitudes when
      unloaded. CONCLUSIONS: The study results suggest that the motor should not be
      operated with the fork in the unloaded state. Anti-vibration gloves are not
      effective at attenuating the vibration frequencies produced by these forks, and
      they may even amplify the transmitted vibration and increase hand/arm fatigue.
      While regular work gloves are suitable, vibration-reducing gloves may not be
      appropriate for use with these tools. These considerations may also be generally
      applicable for the use of motorized forks in other workplace environments.

PMID- 22952388
TI  - Improved early identification of arthritis: evaluating the efficacy of Early
      Arthritis Recognition Clinics.
AB  - OBJECTIVE: Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a
      rheumatologist within 12 weeks after symptom onset; this is mainly due to delay
      at the level of the general practitioner (GP). In order to reduce delay of GPs in
      identifying early arthritis, we initiated an Early Arthritis Recognition Clinic
      (EARC). METHODS: EARCs were initiated at the Leiden and Groningen University
      Medical Centers. At this EARC, patients filled in a questionnaire about their
      symptoms, followed by a short visit with only a full joint examination by an
      experienced rheumatologist. If arthritis was present the patient got an
      appointment the same week at the regular outpatient clinic. The main outcome
      parameter was the GP-delay; the secondary outcome parameter was the total delay.
      In both centres, patients included in early arthritis clinics that had arrived
      via regular referrals served as control group. RESULTS: Four hundred patients
      visited the Leiden EARC and 212 patients the Groningen EARC. Arthritis was
      detected in 42% and 49% respectively. The median GP-delay for these arthritis
      patients was 2.0 (0.4-7.3) and 2.0 (0.4-10.0) weeks and the median total delay
      8.6 (3.6-22.3) and 10.6 (3.1-30.8) weeks respectively. At these two clinics 59%
      and 51% of all arthritis patients and 65% and 53% of the patients that were
      subsequently diagnosed with undifferentiated arthritis or RA were seen within 12
      weeks after symptom onset. In the Leiden and Groningen control groups that
      arrived via regular referrals, only 32% and 38% were seen within 12 weeks time.
      CONCLUSIONS: The EARC increased the early identification of arthritis and RA.

PMID- 22952389
TI  - Bayesian partitioning for mapping disease risk using a matched case-control
      approach to confounding.
AB  - Disease maps are useful for exploring geographical heterogeneity in health
      outcomes. Typically interest lies in unearthing atypical regions after adjusting
      for known confounders. This paper presents a Bayesian partitioning approach for
      analyses when individual-level matching has been used to control confounding. The
      model makes few assumptions about the surface form and, in particular, permits
      discontinuity. The specification is inherently parsimonious and posterior
      sampling permits direct assessment of surface uncertainty; additional unmatched
      covariates can also be incorporated. The method is used to investigate spatial
      variation in perinatal mortality in the North-West Thames region, England.

PMID- 22952390
TI  - Subversion of cell signaling by pathogens.
AB  - Pathogens exploit several eukaryotic signaling pathways during an infection. They
      have evolved specific effectors and toxins to hijack host cell machinery for
      their own benefit. Signaling molecules are preferentially targeted by pathogens
      because they globally regulate many cellular processes. Both viruses and bacteria
      manipulate and control pathways that regulate host cell survival and shape,
      including MAPK signaling, G-protein signaling, signals controlling cytoskeletal
      dynamics, and innate immune responses.

PMID- 22952392
TI  - Wnt proteins.
AB  - Wnt proteins comprise a major family of signaling molecules that orchestrate and
      influence a myriad of cell biological and developmental processes. Although our
      understanding of the role of Wnt signaling in regulating development and
      affecting disease, such as cancer, has been ever increasing, the study of the Wnt
      proteins themselves has been painstaking and slow moving. Despite advances in the
      biochemical characterization of Wnt proteins, many mysteries remain unsolved. In
      contrast to other developmental signaling molecules, such as fibroblast growth
      factors (FGF), transforming growth factors (TGFbeta), and Sonic hedgehog (Shh),
      Wnt proteins have not conformed to many standard methods of protein production,
      such as bacterial overexpression, and analysis, such as ligand-receptor binding
      assays. The reasons for their recalcitrant nature are likely a consequence of the
      complex set of posttranslational modifications involving several highly
      specialized and poorly characterized processing enzymes. With the recent
      description of the first Wnt protein structure, the time is ripe to uncover and
      possibly resolve many of the remaining issues surrounding Wnt proteins and their
      interactions. Here we describe the process of maturation of Wnt from its initial
      translation to its eventual release from a cell and interactions in the
      extracellular environment.

PMID- 22952391
TI  - Treg cells, life history, and diversity.
AB  - Regulatory T cells expressing the FoxP3 transcription factor have a profound and
      nonredundant role in several aspects of immunological tolerance. We will review
      here the specification of this lineage, its population dynamics, and the
      diversity of subphenotypes that correlate with their diverse roles in controlling
      inflammation in a variety of settings.

PMID- 22952393
TI  - Wnt pathway regulation of embryonic stem cell self-renewal.
AB  - Embryonic stem cells (ESCs) can generate all of the cell types found in the adult
      organism. Remarkably, they retain this ability even after many cell divisions in
      vitro, as long as the culture conditions prevent differentiation of the cells.
      Wnt signaling and beta-catenin have been shown to cause strong effects on ESCs
      both in terms of stimulating the expansion of stem cells and stimulating
      differentiation toward lineage committed cell types. The varied effects of Wnt
      signaling in ESCs, alongside the sometimes unconventional mechanisms underlying
      the effects, have generated a fair amount of controversy and intrigue regarding
      the role of Wnt signaling in pluripotent stem cells. Insights into the mechanisms
      of Wnt function in stem cells can be gained by examination of the causes for
      seemingly opposing effects of Wnt signaling on self-renewal versus
      differentiation.

PMID- 22952394
TI  - Transcriptional networks in liver and intestinal development.
AB  - The development of the gastrointestinal tract is a complex process that
      integrates signaling processes with downstream transcriptional responses. Here,
      we discuss the regionalization of the primitive gut and formation of the
      intestine and liver. Anterior-posterior position in the primitive gut is
      important for establishing regions that will become functional organs.
      Coordination of signaling between the epithelium and mesenchyme and downstream
      transcriptional responses is required for intestinal development and homeostasis.
      Liver development uses a complex transcriptional network that controls the
      establishment of organ domains, cell differentiation, and adult function.
      Discussion of these transcriptional mechanisms gives us insight into how the
      primitive gut, composed of simple endodermal cells, develops into multiple
      diverse cell types that are organized into complex mature organs.

PMID- 22952397
TI  - PI3K-PKB/Akt pathway.

PMID- 22952395
TI  - Adipogenesis.
AB  - Adipose tissue is an important site for lipid storage, energy homeostasis, and
      whole-body insulin sensitivity. It is important to understand the mechanisms
      involved in adipose tissue development and function, which can be regulated by
      the endocrine actions of various peptide and steroid hormones. Recent studies
      have revealed that white and brown adipocytes can be derived from distinct
      precursor cells. This review will focus on transcriptional control of
      adipogenesis and its regulation by several endocrine hormones. The general
      functions and cellular origins of adipose tissue and how the modulation of
      adipocyte development pertains to metabolic disease states will also be
      considered.

PMID- 22952396
TI  - Metabolic stress in autophagy and cell death pathways.
AB  - Growth factors and oncogenic kinases play important roles in stimulating cell
      growth during development and transformation. These processes have significant
      energetic and synthetic requirements and it is apparent that a central function
      of growth signals is to promote glucose metabolism to support these demands.
      Because metabolic pathways represent a fundamental aspect of cell proliferation
      and survival, there is considerable interest in targeting metabolism as a means
      to eliminate cancer. A challenge, however, is that molecular links between
      metabolic stress and cell death are poorly understood. Here we review current
      literature on how cells cope with metabolic stress and how autophagy, apoptosis,
      and necrosis are tightly linked to cell metabolism. Ultimately, understanding of
      the interplay between nutrients, autophagy, and cell death will be a key
      component in development of new treatment strategies to exploit the altered
      metabolism of cancer cells.

PMID- 22952400
TI  - Ophthalmological factors influencing visual asthenopia as a result of viewing 3D
      displays.
AB  - AIMS: To identify ophthalmological factors influencing asthenopia as a result of
      viewing three-dimensional (3D) displays. METHODS: Thirty adult subjects without
      ophthalmological abnormality watched the same 3D displays for 30 min. Each
      subject's near point of accommodation (NPA) and convergence (NPC), amplitude of
      fusional convergence and divergence, stereopsis, tear break-up time and
      temperature of ocular surface, and angle of phoric deviation were measured before
      and after viewing the 3D displays. In addition, a survey for subjective symptoms
      was conducted immediately following the viewing of the 3D displays. The above
      mentioned experiments were performed equally with two-dimensional (2D) displays
      in the same 30 subjects for detection of innate influence of 3D displays.
      RESULTS: The NPA and NPC in the subjects were significantly altered after
      watching the 3D displays (p<0.05) as compared with 2D displays. In addition, all
      of the 10 subjective symptoms measured were significantly increased after
      watching 3D displays (p<0.05). CONCLUSIONS: Accommodation and binocular vergence
      are predominant ophthalmological factors that may influence asthenopia
      significantly following the viewing of 3D displays. Subjective visual discomfort
      also significantly increased following the viewing of 3D displays. And there is
      the need for more detailed evaluation for detecting the practically related
      factors with asthenopia.

PMID- 22952401
TI  - Endoscope-assisted pars plana vitrectomy in severe ocular trauma.
AB  - PURPOSE: To report the results of pars plana vitrectomy (PPV) assisted by
      ophthalmic endoscope (OE) in severe ocular trauma cases which are unsuitable for
      PPV using wide-angle contact/non-contact lens due to media haze and/or
      disorganised anterior segment. METHODS: Prospective, non-comparative,
      interventional case series. Main outcome measured was anatomic status of the
      retina postoperatively, secondary outcome measured was functional status
      regarding vision, intraocular pressure and control of inflammation in cases of
      endophthalmitis. RESULTS: Fifty trauma cases were included in the study. Out of
      these, 43 eyes had open globe injuries (32 eyes without intraocular foreign body
      (IOFB), and 11 eyes with retained IOFB), and seven eyes had post-traumatic
      endophthalmitis. In the open globe injury group, 36 (83.7%) eyes reported
      improvement in vision. In endophthalmitis group, five eyes showed improvement in
      vision. CONCLUSIONS: OE provided a clear view to conduct PPV in select trauma
      cases where delay in surgery due to hazy media or due to non-availability of
      donor cornea for simultaneous penetrating keratoplasty can lead to severe
      proliferative vitreoretinopathy changes.

PMID- 22952398
TI  - Mitochondrial evolution.
AB  - Viewed through the lens of the genome it contains, the mitochondrion is of
      unquestioned bacterial ancestry, originating from within the bacterial phylum
      alpha-Proteobacteria (Alphaproteobacteria). Accordingly, the endosymbiont
      hypothesis--the idea that the mitochondrion evolved from a bacterial progenitor
      via symbiosis within an essentially eukaryotic host cell--has assumed the status
      of a theory. Yet mitochondrial genome evolution has taken radically different
      pathways in diverse eukaryotic lineages, and the organelle itself is increasingly
      viewed as a genetic and functional mosaic, with the bulk of the mitochondrial
      proteome having an evolutionary origin outside Alphaproteobacteria. New data
      continue to reshape our views regarding mitochondrial evolution, particularly
      raising the question of whether the mitochondrion originated after the eukaryotic
      cell arose, as assumed in the classical endosymbiont hypothesis, or whether this
      organelle had its beginning at the same time as the cell containing it.

PMID- 22952399
TI  - Herpes simplex viruses: mechanisms of DNA replication.
AB  - Herpes simplex virus (HSV) encodes seven proteins necessary for viral DNA
      synthesis-UL9 (origin-binding protein), ICP8 (single-strand DNA [ssDNA]-binding
      protein), UL30/UL42 (polymerase), and UL5/UL8/UL52 (helicase/primase). It is our
      intention to provide an up-to-date analysis of our understanding of the
      structures of these replication proteins and how they function during HSV
      replication. The potential roles of host repair and recombination proteins will
      also be discussed.

PMID- 22952402
TI  - Comparison of posterior capsule opacification between a 1-piece and a 3-piece
      microincision intraocular lens.
AB  - OBJECTIVE: To compare the intensity of posterior capsular opacification (PCO)
      between a 1-piece and a 3-piece microincision cataract surgery intraocular lens
      (MICS IOL) in a prospective randomised study. METHODS: 80 eyes of 40 patients
      with age-related cataract were enrolled in this study. Each patient received a 1
      piece MICS IOL (AF-1 NY-60, Hoya, Tokyo, Japan) in one eye and a 3-piece MICS IOL
      (AF-1 iMICS Y-60H, Tokyo, Hoya) in the other eye. At the 1-year follow-up, the
      patients were examined at the slit lamp, visual acuity was determined and
      standardised high-resolution digital retroillumination images were taken for
      objective quantification of regeneratory PCO using an automated image analysis
      software (AQUA). RESULTS: The mean regeneratory PCO score (1-piece IOL: 0.2, 3
      piece IOL 0.3, p=0.7) and the neodymium:yttrium-aluminium-garnet laser
      capsulotomy rate (two cases in 3-piece IOL group; p=0.5) were comparable low for
      both IOLs. Capsular folds occurred significantly more often in the 3-piece IOL
      group (p=0.02). CONCLUSIONS: Modification of the MICS IOL from a 3-piece to a 1
      piece haptic design caused in short term no significant change in PCO amount.
      Compared with the 3-piece IOL, the 1-piece IOL led to significantly less capsular
      folds 1 year after surgery.

PMID- 22952404
TI  - Mind the gap!

PMID- 22952403
TI  - Lid-parallel conjunctival folds (LIPCOF) and dry eye: a multicentre study.
AB  - AIMS: The study was designed to test the clinical application of the grading of
      lid-parallel conjunctival folds (LIPCOF) as a diagnostic test for dry eye.
      METHODS: At 12 centres in 11 countries, 272 eyes of 272 dry eye patients (75 men,
      197 women) were examined. Their mean age was 52.7+/-16.2 years. The LIPCOF were
      graded according to the method of Hoh et al. The tear film break-up time (BUT)
      was measured, and fluorescein staining and the Schirmer 1 test were performed.
      The subjective symptoms were evaluated by 16 questions. RESULTS: The LIPCOF score
      demonstrated significant positive correlations with age, dry eye disease severity
      and fluorescein staining (r>0.2, p<0.001), and negative correlations with BUT and
      results of the Schirmer 1 test (r<-0.2, p<0.001). The LIPCOF score exhibited a
      significant correlation with the overall subjective symptoms (r=0.250, p<0.001).
      The sensitivity and specificity of LIPCOF grading for discriminating between
      normal and dry eyes were best with the cut-off between LIPCOF degrees 1 and 2.
      CONCLUSIONS: The displayed medium sensitivity and specificity, and good positive
      predictive value of the LIPCOF test support the use of LIPCOF grading as a
      simple, quick and non-invasive dry eye screening tool.

PMID- 22952405
TI  - Characterisation of mouse limbal neurosphere cells: a potential cell source of
      functional neurons.
AB  - BACKGROUND/AIMS: To characterise the origin, ultrastructure and functional
      properties of corneal limbal neurospheres (LNS). METHODS: Limbal cells were
      isolated from the corneal limbus of adult mice and cultured in a serum-free
      sphere forming culture system. LNS were characterised by immunocytochemistry,
      Reverse-transcription-PCR and electron microscopy. LNS cells were also cocultured
      with neonatal mouse retinal cells. Phenotype and function were then assessed by
      immunofluorescence and a calcium influx/efflux assay. RESULTS: LNS cells
      displayed clonal growth and self-renewal, and expressed a wide range of stem cell
      and neural lineage markers. The acquisition of neural properties was concordant
      with expression of neural crest markers including CD34, Sca1, Sox9, Twist1, but
      not CD45. LNS exhibited similar morphology and microstructure to neurospheres
      derived from the central nervous system. Following culture in a conducive
      environment, the derived cells displayed mature neural markers and exhibited
      electrical excitability. CONCLUSIONS: Corneal limbal stromal progenitor cells are
      a potential and convenient autologous cell source to generate functional neurons.

PMID- 22952406
TI  - Doppler ultrasound and tibial tuberosity maturation status predicts pain in
      adolescent male athletes with Osgood-Schlatter's disease: a case series with
      comparison group and clinical interpretation.
AB  - BACKGROUND: The pathogenesis of the Osgood-Schlatter's disease (OSD) is still
      debated. The fragmentation of the ossification centre has been questioned as a
      definitive sign of OSD and has been seen as a normal development of the anterior
      tibial tubercle (ATT). OBJECTIVES: It is unknown if such changes are present in
      the presumed pathological tendon insertion seen in OSD, nor the relation of
      Doppler-positive changes to pain on clinical examination. METHODS: A prospective
      analysis was carried out on 20 consecutive symptomatic male athletes (13.9
      years+/-1.3) and a comparison group of asymptomatic subjects. All underwent a
      comparative clinical assessment and ultrasound with colour Doppler scan on both
      knees. Subjective pain was recorded with a visual analogue scale (VAS) during
      provocative manoeuvres: palpation, resisted contraction and single leg squat.
      RESULTS: Positive Doppler US (within the distal end of the patellar tendon) was
      associated with higher pain on palpation (47+/-24.5 vs 18+/-11.4, p<0.01) and
      resisted static contraction (59+/-20.2 vs 27+/-12.5, p<0.001) compared with
      Doppler-negative subjects. No Doppler activity was found in the comparison group.
      VAS for palpation and resisted contraction of the athletes graded as stage 2
      (51.1+/-22.0 and 60.0+/-21.2) were significantly higher than stage 3 (17.8+/-12.0
      and 18.9+/-16.9) and stage 4 (15.0+/-7.1 and 25.0+/-7.1; p<0.01). CONCLUSIONS:
      More painful OSD is associated with the presence of neo-vessels. This may be
      linked with a particular stage of ATT maturation and applied compressive forces.
      A Doppler ultrasound scan adds practical information to develop the care plan of
      the patient.

PMID- 22952407
TI  - Radiofrequency denervation of the inguinal ligament for the treatment of
      'Sportsman's Hernia': a pilot study.
AB  - BACKGROUND: Chronic groin pain is a common and debilitating condition in highly
      active athletes. Symptoms are often ascribed to the so-called Sportsman's Hernia,
      and these patients frequently undergo prolonged and often painful remedial
      physiotherapy, or, if the condition is refractory, surgery to repair the
      posterior inguinal wall. HYPOTHESIS: We hypothesised that radiofrequency
      denervation (RFD) of both the ilioinguinal nerve and inguinal ligament could be
      used to desensitise the groin region and enable the athlete to become pain-free.
      STUDY DESIGN: A prospective randomised controlled trial of three groups of
      patients with chronic groin pain. METHODS: Thirty-six patients with chronic groin
      pain of greater than 6 months duration, with no identifiable structural cause and
      which was refractory to conservative treatment, were randomised into two groups.
      Group 1 was treated with RFD (n=18), while group 2 was treated with local
      anaesthetic (Bupivicaine) and steroid (Trimacinolone) injection (n=18). A further
      10 patients with previous failed surgery for the same condition were treated with
      RFD without randomisation. All patients then underwent a standardised
      physiotherapy regimen. The Visual Analogue Scale at rest (VASr) and with activity
      (VASa) was used to assess pain, and London Adductor and Abdominal Groin Score was
      used to assess function, at baseline and at 1 week, 3 months and 6 months post
      treatment. RESULTS: RFD treatment resulted in a significant improvement above
      baseline in all measures and at each time intervals up to 6 months, in both the
      randomised Group 1 and in the postsurgery group (p values ranging from <0.001 to
      0.001). Injection of local anaesthetic and steroid resulted in a significant
      improvement above baseline in all measures, but only at 1 week (p values ranging
      from 0.001 to 0.021), and not at any of the later intervals. Improvements in all
      measures was significantly greater in Group 1 than in Group 2 at all follow-up
      intervals (p values ranging from <0.001 to 0.003). No persistent adverse events
      were recorded. CONCLUSIONS: The use of RFD in the treatment of refractory
      Sportsman's Hernia is safe and efficacious at least in the short term, and is
      superior to anaesthetic/steroid injection. The results suggest that symptoms are
      related to tendon inflammation and ilioinguinal nerve compression, and can be
      abolished with pharmacological or radiofrequency treatment, without the need for
      surgery. CLINICAL RELEVANCE: This novel technique could help athletes suffering
      from chronic groin pain return to play more quickly, both facilitating and
      allowing deferral of remedial physiotherapy treatments, and potentially avoiding
      the need for surgery.

PMID- 22952408
TI  - Biological colloid engineering: Self-assembly of dipolar ferromagnetic chains in
      a functionalized biogenic ferrofluid.
AB  - We have studied the dynamic behavior of nanoparticles in ferrofluids consisting
      of single-domain, biogenic magnetite (Fe(3)O(4)) isolated from Magnetospirillum
      magnetotacticum (MS-1). Although dipolar chains form in magnetic colloids in zero
      applied field, when dried upon substrates, the solvent front disorders
      nanoparticle aggregation. Using avidin-biotin functionalization of the particles
      and substrate, we generated self-assembled, linear chain motifs that resist
      solvent front disruption in zero-field. The engineered self-assembly process we
      describe here provides an approach for the creation of ordered magnetic
      structures that could impact fields ranging from micro-electro-mechanical systems
      development to magnetic imaging of biological structures.

PMID- 22952409
TI  - Characterization of the transport topology in patient-specific abdominal aortic
      aneurysm models.
AB  - Abdominal aortic aneurysm (AAA) is characterized by disturbed blood flow patterns
      that are hypothesized to contribute to disease progression. The transport
      topology in six patient-specific abdominal aortic aneurysms was studied. Velocity
      data were obtained by image-based computational fluid dynamics modeling, with
      magnetic resonance imaging providing the necessary simulation parameters. Finite
      time Lyapunov exponent (FTLE) fields were computed from the velocity data, and
      used to identify Lagrangian coherent structures (LCS). The combination of FTLE
      fields and LCS was used to characterize topological flow features such as
      separation zones, vortex transport, mixing regions, and flow impingement. These
      measures offer a novel perspective into AAA flow. It was observed that all
      aneurysms exhibited coherent vortex formation at the proximal segment of the
      aneurysm. The evolution of the systolic vortex strongly influences the flow
      topology in the aneurysm. It was difficult to predict the vortex dynamics from
      the aneurysm morphology, motivating the application of image-based flow modeling.

PMID- 22952410
TI  - Comparison of the robustness and functionality of three adrenaline auto
      injectors.
AB  - BACKGROUND: Anaphylaxis is a medical emergency that requires the intramuscular
      injection of adrenaline using an adrenaline auto-injector (AAI). This study
      compared the robustness and performance characteristics of three AAIs available
      in Europe. METHODS: Three AAIs (Jext((r)), EpiPen((r)), and Anapen((r))) were
      tested in terms of the force needed to activate the AAIs, exposed needle length,
      injection volume, and injection time. Three conditions were used to assess
      robustness: base conditions, after three successive free-fall drops from 1.5 m,
      and after a 40 kg static load challenge. The injection depth and estimated volume
      of solution delivered into ballistic gelatin were also assessed. RESULTS: Less
      force was required to remove the safety cap from Jext and EpiPen than from Anapen
      under base conditions. The required force was unaffected by free-fall drop tests,
      whereas the static load test significantly increased the force required to remove
      the safety cap from Jext (difference from base value 7.7 N; P < 0.001) and from
      EpiPen ( difference from base value 30.3 N; P < 0.001). Two Anapens could not be
      activated after the free-fall and static load tests. The mean exposed needle
      length was 15.36 mm (standard error [SE] 0.04) for Jext, 15.02 mm (SE 0.05) for
      EpiPen, and 7.49 mm (SE 0.15) for Anapen. The mean maximum injection depth in
      gelatin within 10 seconds was 28.87 mm (standard deviation [SD] 0.73) for Jext,
      29.68 mm (SD 2.08) for EpiPen, and 18.74 mm (SD 1.25) for Anapen. CONCLUSION: A
      comparison of the robustness and performance characteristics of the three AAIs
      showed that cartridge-based devices (Jext and EpiPen) appeared to be
      significantly more robust and capable of rapidly and consistently delivering the
      correct dose of adrenaline to the correct tissue compartment than the syringe
      based Anapen. Overall, Jext performed better than EpiPen or Anapen following
      mechanical stress designed to mimic real-world use.

PMID- 22952411
TI  - Potential role of linagliptin as an oral once-daily treatment for patients with
      type 2 diabetes.
AB  - BACKGROUND: Linagliptin is an oral antihyperglycemic agent that selectively
      inhibits the enzyme dipeptidyl peptidase-4 (DPP-4). Inhibition of DPP-4 increases
      the levels of the incretin hormones glucagon-like peptide and glucose-dependent
      insulinotropic polypeptide by preventing their degradation. OBJECTIVE: We
      reviewed the role of linagliptin as an oral once-daily treatment for patients
      with type 2 diabetes. METHODS: A comprehensive literature search was performed
      using the term "linagliptin." Original research articles and review articles were
      included in our examination. RESULTS: Linagliptin has a similar mode of action as
      other gliptins, with comparable efficacy, safety profile, and tolerability.
      Differences in pharmacokinetic parameters that distinguish linagliptin from other
      gliptins include that linagliptin is not renally excreted and does not require
      dose reduction with renal impairment. CONCLUSION: Linagliptin is an oral, once
      daily, antihyperglycemic agent that significantly reduces glycated hemoglobin
      (HbA(1c)) when used alone or in combination with other antidiabetic drugs in
      people with type 2 diabetes. Pharmacokinetics, such as the lack of renal
      excretion, distinguishes linagliptin from other gliptins.

PMID- 22952412
TI  - Impact of physical activity and bodyweight on health-related quality of life in
      people with type 2 diabetes.
AB  - PURPOSE: Increasing obesity prevalence rates in the general population are
      reflected in patients with type 2 diabetes. Health-related quality of life
      (HRQoL) is negatively affected in patients who are overweight or have diabetes,
      but physical activity (PA) is proven to have positive side effects on the
      perceived quality of life. Little is known about the relationship of PA with
      obesity, diabetes, and HRQoL. Therefore, the objective of the present study was
      to examine the relationship between HRQoL and PA in type 2 diabetics in
      association with the severity of overweight. METHODS: This was a cross-sectional
      multicenter cohort study involving 370 outpatients with type 2 diabetes.
      Participants completed the SF-36 Health Survey (SF-36((r))) and the Freiburger
      Questionnaire for Physical Activity (FFkA). Endurance capacity was tested with a
      2 km walking test. t-tests, analysis of variance, Pearson's correlation test, and
      multiple regression analyses were performed. RESULTS: HRQoL is negatively
      affected by body mass index (BMI). The results show that patients with type 2
      diabetes and grade II obesity (BMI > 35) have a lower HRQoL than overweight
      patients (BMI 25-29.99) and patients with grade I obesity (BMI 30-35). HRQoL
      decreases with decreasing PA in all dimensions of the SF-36. PA remains a
      significant predictor of physical composite summary (B = 0.09; beta = 0.11; P <
      0.05), physical function (B = 0.10; beta = 0.13; P < 0.01), mental composite
      summary (B = 0.13; beta = 0.20; P < 0.001), vitality (B = 0.15; beta = 0.24; P <
      0.001), and psychological well-being (B = 0.11; beta = 0.18; P < 0.01) when
      controlling for age, sex, and BMI. CONCLUSION: Because of the strong association
      between being overweight/obese and several risk factors for morbidity and
      mortality, reversing the obesity epidemic is an urgent priority. Based upon the
      results of this study and the available evidence of the efficacy of PA for
      preventing and treating those who are overweight or obese, health care
      professionals should continue to stress the importance of PA as a treatment
      option.

PMID- 22952413
TI  - The role of TIM-containing molecules in airway disease and their potential as
      therapeutic targets.
AB  - T cell immunoglobulin and mucin-domain (TIM)-containing molecules have emerged as
      promising therapeutic targets to correct abnormal immune function in several
      autoimmune and chronic inflammatory conditions. Despite the initial discovery
      linking TIM-containing molecules and the airway hyperreactivity regulatory locus
      in mice, there is a paucity of studies on the function of TIM-containing
      molecules in lung inflammatory disease. Initially, studies were limited to mice
      models of asthma. More recently however, TIM-containing molecules have been
      implicated in an ever-expanding list of airway conditions that includes
      pneumonia, tuberculosis, influenza, sarcoidosis, lung cancer, and cystic
      fibrosis. This present review discusses the role of TIM-containing molecules and
      their ligands in the lung, as well as their potential as therapeutic targets in
      airway disease.

PMID- 22952414
TI  - Ex vivo stimulation of whole blood as a means to determine glucocorticoid
      sensitivity.
AB  - PURPOSE: Glucocorticoids are commonly prescribed to treat a number of diseases
      including the majority of inflammatory diseases. Despite considerable
      interpersonal variability in response to glucocorticoids, an insensitivity rate
      of about 30%, and the risk of adverse side effects of glucocorticoid therapy,
      currently no assay is performed to determine sensitivity. PATIENTS AND METHODS:
      Here we propose a whole blood ex vivo stimulation assay to interrogate known
      glucocorticoid receptor (GR) up- and downregulated genes to indicate
      glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to
      provide a relatively fast and inexpensive assay. RESULTS: We show that the GR
      regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment
      with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFalpha) are
      repressed by dexamethasone in a dose responsive manner. There is considerable
      interpersonal variability in the maximum induction of these genes but little
      variation in the EC(50) and IC(50) concentrations. The regulation of the GR
      induced genes differs throughout the day whereas the suppression of LPS-induced
      cytokines is not as sensitive to time of day. CONCLUSION: In all, this assay
      would provide a method to determine glucocorticoid receptor responsiveness in
      whole blood.

PMID- 22952416
TI  - Cost-effectiveness of screening for hepatocellular carcinoma: putting the cart
      before the horse.

PMID- 22952415
TI  - Economics of less invasive spinal surgery: an analysis of hospital cost
      differences between open and minimally invasive instrumented spinal fusion
      procedures during the perioperative period.
AB  - BACKGROUND: There is great debate about the costs and benefits of technology
      driven medical interventions such as instrumented lumbar fusion. With most
      analyses using charge data, the actual costs incurred by medical institutions
      performing these procedures are not well understood. The object of the current
      study was to examine the differences in hospital operating costs between open and
      minimally invasive spine surgery (MIS) during the perioperative period. METHODS:
      Data were collected in the form of a prospective registry from a community
      hospital after specific Institutional Review Board approval was obtained. The
      analysis included consecutive adult patients being surgically treated for
      degenerative conditions of the lumbar spine, with either an MIS or open approach
      for two-level instrumented lumbar fusion. Patient outcomes and costs were
      collected for the perioperative period. Hospital operating costs were grouped by
      hospitalization/operative procedure, transfusions, reoperations, and residual
      events (health care interactions). RESULTS: One hundred and one open posterior
      lumbar interbody fusion (Open group) and 109 MIS patients were treated primarily
      for stenosis coupled with instability (39.6% and 59.6%, respectively). Mean total
      hospital costs were $27,055.53 for the Open group and $24,320.16 for the MIS
      group. This represents a statistically significant cost savings of $2,825.37
      (10.4% [95% confidence interval: $522.51-$5,128.23]) when utilizing MIS over
      traditional Open techniques. Additionally, residual events, complications, and
      blood transfusions were significantly more frequent in the Open group, compared
      to the MIS group. CONCLUSIONS/LEVEL OF EVIDENCE: Utilizing minimally invasive
      techniques for instrumented spinal fusion results in decreased hospital operating
      costs compared to similar open procedures in the early perioperative period.
      Additionally, patient benefits of minimally invasive techniques include
      significantly less blood loss, shorter hospital stays, lower complication rate,
      and a lower number of residual events. Long-term outcome comparisons are needed
      to evaluate the efficacy of the two treatments. LEVEL OF EVIDENCE: III  CLINICAL
      RELEVANCE: This work represents a true cost-of-operating comparison between open
      and MIS approaches for lumbar spine fusion, which has relevance to surgeons,
      hospitals and payers in medical decision-making.

PMID- 22952417
TI  - Dupuytren's Contracture in Alabama HFE Hemochromatosis Probands.
AB  - BACKGROUND: Dupuytren's contracture (DC) and HFE hemochromatosis occur in some of
      the same at-risk populations and present with similar comorbid conditions.
      METHODS: We estimated DC prevalence in two cohorts of white Alabama
      hemochromatosis probands (294 C282Y homozygotes, 67 C282Y/H63D compound
      heterozygotes) in a retrospective study. We performed logistic regressions on DC
      using the following independent variables: age, body mass index, heavy ethanol
      consumption, serum ferritin, elevated serum AST/ALT, non-alcoholic fatty liver
      disease, viral hepatitis, cirrhosis, and diabetes. RESULTS: One man and two women
      with C282Y homozygosity had DC (prevalence 1.02%; 95% CI 0.35%-2.96%). A man with
      C282Y/H63D had DC (prevalence 1.49%; 95% CI 0.26%-7.98%). DC occurred as an
      autosomal dominant trait in his kinship. In regression analyses, no single
      variable predicted DC. We observed no new DC cases after the diagnosis of
      hemochromatosis (mean follow-up 12.9 +/- 7.5 years (1 SD), and 9.0 +/- 5.1 years,
      respectively). CONCLUSIONS: Our prevalence estimates of DC in white Alabama
      hemochromatosis probands are similar to those found in the white US population
      cohorts. DC risk was unrelated to the variables we studied.

PMID- 22952418
TI  - Electrocardiographic and Electrophysiologic Insights into Atrioventricular Nodal
      Re-entry Tachycardia: Diagnostic Update.
AB  - Atrioventricular nodal re-entry tachycardia is a common supraventricular
      arrhythmia. The rate of recurrence is relatively high, and accordingly ablative
      therapy became the first-line suggested therapy. In this review, we highlight the
      electrocardiographic clues to the diagnosis of atrioventricular nodal re-entry
      tachycardia, also we present the electrophysiological data and maneuvers that
      enable the ruling out of other supraventricular tachycardias and ensure an
      accurate and specific diagnosis of atrioventricular nodal reentrant tachycardia.

PMID- 22952419
TI  - TAVR and SAVR: Current Treatment of Aortic Stenosis.
AB  - Transcatheter aortic valve replacement (TAVR) was approved in the United States
      in late 2011, providing a critically needed alternative therapy for patients with
      severe aortic stenosis previously refused surgical aortic valve replacement
      (SAVR). Over 20,000 TAVR have been performed in patients worldwide since 2002
      when Alain Cribier performed the first-in-man TAVR. This paper reviews the data
      from balloon expandable and self-expanding aortic stent valves as well as data
      comparing them with traditional surgical aortic valve replacement (SAVR).
      Complications using criteria established by the Valve Academic Research
      Consortium (VARC) are reviewed. Future challenges and possibilities are discussed
      and will make optimizing TAVR an important goal in the years to come.

PMID- 22952420
TI  - Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and
      tumors.
AB  - The epidermal growth factor receptor (EGFR) has been targeted for inhibition
      using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in
      outcome in subsets of patients with head and neck, lung, and colorectal
      carcinomas. We have previously found that EGFR stability plays a key role in cell
      survival after chemotherapy and radiotherapy. Heat shock protein 90 (HSP90) is
      known to stabilize mutant EGFR and ErbB2, but its role in cancers with wild-type
      (WT) WT-EGFR is unclear. In this report, we demonstrate that fully mature,
      membrane-bound WT-EGFR interacts with HSP90 independent of ErbB2. Further, the
      HSP90 inhibitors geldanamycin (GA) and AT13387 cause a decrease in WT-EGFR in
      cultured head and neck cancer cells. This decrease results from a significantly
      reduced half-life of WT-EGFR. WT-EGFR was also lost in head and neck xenograft
      specimens after treatment with AT13387 under conditions that inhibited tumor
      growth and prolonged survival of the mice. Our findings demonstrate that WT-EGFR
      is a client protein of HSP90 and that their interaction is critical for
      maintaining both the stability of the receptor as well as the growth of EGFR
      dependent cancers. Furthermore, these findings support the search for specific
      agents that disrupt HSP90's ability to act as an EGFR chaperone.

PMID- 22952421
TI  - Integrin-associated CD151 drives ErbB2-evoked mammary tumor onset and metastasis.
AB  - ErbB2+ human breast cancer is a major clinical problem. Prior results have
      suggested that tetraspanin CD151 might contribute to ErbB2-driven breast cancer
      growth, survival, and metastasis. In other cancer types, CD151 sometimes supports
      tumor growth and metastasis. However, a definitive test of CD151 effects on de
      novo breast cancer initiation, growth, and metastasis has not previously been
      done. We used CD151 gene-deleted mice expressing the MMTV-ErbB2 transgene to show
      that CD151 strongly supports ErbB2+ mammary tumor initiation and metastasis.
      Delayed tumor onset (by 70-100 days) in the absence of CD151 was accompanied by
      reduced survival of mammary epithelial cells and impaired activation of FAK- and
      MAPK-dependent pathways. Both primary tumors and metastatic nodules showed
      smooth, regular borders, consistent with a less invasive phenotype. Furthermore,
      consistent with impaired oncogenesis and decreased metastasis, CD151-targeted MCF
      10A/ErbB2 cells showed substantial decreases in three-dimensional colony
      formation, EGF-stimulated tumor cell motility, invasion, and transendothelial
      migration. These CD151-dependent functions were largely mediated through
      alpha6beta4 integrin. Moreover, CD151 ablation substantially prevented PKC- and
      EGFR/ERK-dependent alpha6beta4 integrin phosphorylation, consistent with
      retention of epithelial cell polarity and intermediate filament cytoskeletal
      connections, which helps to explain diminished metastasis. Finally, clinical data
      analyses revealed a strong correlation between CD151 and ErbB2 expression and
      metastasis-free survival of breast cancer patients. In conclusion, we provide
      strong evidence that CD151 collaborates with LB integrins (particularly
      alpha6beta4 and ErbB2 (and EGFR) receptors to regulate multiple signaling
      pathways, thereby driving mammary tumor onset, survival, and metastasis.
      Consequently, CD151 is a useful therapeutic target in malignant ErbB2+ breast
      cancer.

PMID- 22952422
TI  - Stromal cell-derived factor 1alpha mediates resistance to mTOR-directed therapy
      in pancreatic cancer.
AB  - PURPOSE: The factors preventing the translation of preclinical findings
      supporting the clinical development mTOR-targeted therapy in pancreatic cancer
      therapy remain undetermined. Stromal cell.derived factor 1alpha (SDF-1alpha)
      CXCR4 signaling was examined as a representative microenvironmental factor able
      to promote mTOR-targeted therapy resistance in pancreatic cancer. EXPERIMENTAL
      DESIGN: Primary pancreas explant xenografts and in vitro experiments were used to
      perform pharmacodynamic analyses of SDF-1alpha-CXCR4 regulation of the mTOR
      pathway. Combinatorial effects of CXCR4, EGFR, and mTOR pharmacologic inhibition
      were evaluated in temsirolimus-resistant and -sensitive xenografts. Intratumoral
      gene and protein expressions of mTOR pathway effectors cyclin D1, c-Myc, and VEGF
      were evaluated. RESULTS: Baseline intratumoral SDF-1alpha gene expression
      correlated with temsirolimus resistance in explant models. SDF-1alpha stimulation
      of pancreatic cells resulted in CXCR4-mediated PI3-kinase-dependent S6-RP
      phosphorylation (pS6-RP) on exposure to temsirolimus. Combinatorial therapy with
      AMD3465 (CXCR4 small-molecule inhibitor) and temsirolimus resulted in effective
      tumor growth inhibition to overcome temsirolimus resistance. In contrast, SDF
      1alpha exposure induced a temsirolimus-resistant phenotype in temsirolimus
      sensitive explants. AMD3465 inhibited CXCR4-mediated intratumoral S6-RP
      phosphorylation and cyclin D and c-myc gene expression. Next, CXCR4 promoted
      intratumoral EGFR expression in association with temsirolimus resistance.
      Treatment with AMD3465, temsirolimus- and erlotinib-mediated tumor growth
      inhibition to overcome temsirolimus resistance in the explant model. Lastly, SDF
      1alpha-CXCR4 signaling increased intratumoral VEGF gene and protein expression.
      CONCLUSIONS: SDF-1alpha-CXCR4 signaling represents a microenvironmental factor
      that can maintain mTOR pathway fidelity to promote resistance to mTOR-targeted
      therapy in pancreatic cancer by a variety of mechanisms such as recruitment of
      EGFR signaling and angiogenesis.

PMID- 22952423
TI  - Gene fusions associated with recurrent amplicons represent a class of passenger
      aberrations in breast cancer.
AB  - Application of high-throughput transcriptome sequencing has spurred highly
      sensitive detection and discovery of gene fusions in cancer, but distinguishing
      potentially oncogenic fusions from random, "passenger" aberrations has proven
      challenging. Here we examine a distinctive group of gene fusions that involve
      genes present in the loci of chromosomal amplifications--a class of oncogenic
      aberrations that are widely prevalent in breast cancers. Integrative analysis of
      a panel of 14 breast cancer cell lines comparing gene fusions discovered by high
      throughput transcriptome sequencing and genome-wide copy number aberrations
      assessed by array comparative genomic hybridization, led to the identification of
      77 gene fusions, of which more than 60% were localized to amplicons including
      17q12, 17q23, 20q13, chr8q, and others. Many of these fusions appeared to be
      recurrent or involved highly expressed oncogenic drivers, frequently fused with
      multiple different partners, but sometimes displaying loss of functional domains.
      As illustrative examples of the "amplicon-associated" gene fusions, we examined
      here a recurrent gene fusion involving the mediator of mammalian target of
      rapamycin signaling, RPS6KB1 kinase in BT-474, and the therapeutically important
      receptor tyrosine kinase EGFR in MDA-MB-468 breast cancer cell line. These gene
      fusions comprise a minor allelic fraction relative to the highly expressed full
      length transcripts and encode chimera lacking the kinase domains, which do not
      impart dependence on the respective cells. Our study suggests that amplicon
      associated gene fusions in breast cancer primarily represent a by-product of
      chromosomal amplifications, which constitutes a subset of passenger aberrations
      and should be factored accordingly during prioritization of gene fusion
      candidates.

PMID- 22952424
TI  - CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel
      chemotherapy.
AB  - Several in vitro and in vivo models have revealed the key role of CXCR4/CXCL12
      axis in tumor-stroma interactions. Stromal cells present in the tumor
      microenvironment express high levels of CXCL12 protein, directly stimulating
      proliferation and migration of CXCR4-expressing cancer cells. This specific
      prosurvival influence of stromal cells on tumor cells is thought to protect them
      from cytotoxic chemotherapy and is postulated as a possible explanation for the
      minimal residual disease in hematological and solid cancers. Therefore,
      CXCR4/CXCL12 signaling is an attractive therapeutic target in cancer, as proven
      in preclinical leukemia mouse models, where CXCR4 inhibition sensitized cancer
      cells to conventional chemotherapy. This study investigates whether inhibition of
      CXCR4 with the specific inhibitor AMD3100 sensitizes human prostate cancer cells
      to docetaxel. We showed that both mouse and human stromal cell lines have a
      protective effect on PC3-luc cells by promoting their survival after
      chemotherapy. Furthermore, we demonstrated that AMD3100 sensitizes PC3-luc cells
      to docetaxel. In a subcutaneous xenograft mouse model of human prostate
      carcinoma, we showed that a combination of docetaxel and AMD3100 exerts increased
      antitumor effect compared with docetaxel alone. We concluded that CXCR4
      inhibition chemosensitizes prostate cancer cells, both in vitro and in vivo. To
      explore the relevance of these findings, we analyzed CXCR4 expression levels in
      human prostate cancer samples. We found that cancer cells present in bone
      metastatic lesions express higher CXCR4 levels relative to the cells present in
      primary tumors and lymph node metastatic lesions. These findings underscore the
      potential of CXCR4 inhibitors as chemosensitizing agents.

PMID- 22952425
TI  - 3-phosphoinositide-dependent kinase 1 controls breast tumor growth in a kinase
      dependent but Akt-independent manner.
AB  - 3-phosphoinositide-dependent protein kinase 1 (PDK1) is the pivotal element of
      the phosphatidylinositol 3 kinase (PI3K) signaling pathway because it
      phosphorylates Akt/PKB through interactions with phosphatidylinositol 3,4,5
      phosphate. Recent data indicate that PDK1 is overexpressed in many breast
      carcinomas and that alterations of PDK1 are critical in the context of oncogenic
      PI3K activation. However, the role of PDK1 in tumor progression is still
      controversial. Here, we show that PDK1 is required for anchorage-independent and
      xenograft growth of breast cancer cells harboring either PI3KCA or KRAS
      mutations. In fact, PDK1 silencing leads to increased anoikis, reduced soft agar
      growth, and pronounced apoptosis inside tumors. Interestingly, these phenotypes
      are reverted by PDK1 wild-type but not kinase-dead mutant, suggesting a relevant
      role of PDK1 kinase activity, even if PDK1 is not relevant for Akt activation
      here. Indeed, the expression of constitutively active forms of Akt in PDK1
      knockdown cells is unable to rescue the anchorage-independent growth. In
      addition, Akt down-regulation and pharmacological inhibition do not inhibit the
      effects of PDK1 overexpression. In summary, these results suggest that PDK1 may
      contribute to breast cancer, even in the absence of PI3K oncogenic mutations and
      through both Akt-dependent and Akt-independent mechanisms.

PMID- 22952426
TI  - Localized hypoxia results in spatially heterogeneous metabolic signatures in
      breast tumor models.
AB  - Tumor hypoxia triggers signaling cascades that significantly affect biologic
      outcomes such as resistance to radiotherapy and chemotherapy in breast cancer.
      Hypoxic regions in solid tumor are spatially heterogeneous. Therefore,
      delineating the origin and extent of hypoxia in tumors is critical. In this
      study, we have investigated the effect of hypoxia on different metabolic
      pathways, such as lipid and choline metabolism, in a human breast cancer model.
      Human MDA-MB-231 breast cancer cells and tumors, which were genetically
      engineered to express red fluorescent tdTomato protein under hypoxic conditions,
      were used to investigate hypoxia. Our data were obtained with a novel three
      dimensional multimodal molecular imaging platform that combines magnetic
      resonance (MR) imaging, MR spectroscopic imaging (MRSI), and optical imaging of
      hypoxia and necrosis. A higher concentration of noninvasively detected total
      choline-containing metabolites (tCho) and lipid CH3 localized in the tdTomato
      fluorescing hypoxic regions indicated that hypoxia can upregulate tCho and lipid
      CH3 levels in this breast tumor model. The increase in tCho under hypoxia was
      primarily due to elevated phosphocholine levels as shown by in vitro MR
      spectroscopy. Elevated lipid CH3 levels detected under hypoxia were caused by an
      increase in mobile MR-detectable lipid droplets, as demonstrated by Nile Red
      staining. Our findings demonstrate that noninvasive MRSI can help delineate
      hypoxic regions in solid tumors by means of detecting the metabolic outcome of
      tumor hypoxia, which is characterized by elevated tCho and lipid CH3.

PMID- 22952429
TI  - Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to
      the apoptotic effects of the protein synthesis inhibitor verrucarin A.
AB  - Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen
      Myrothecium verrucaria and was identified as a selective inhibitor of clear cell
      renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a
      library of naturally occurring small molecules. CCRCC arises as a result of loss
      of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA
      inhibits protein translation initiation culminating in apoptosis through the
      extrinsic signaling pathway. Reintroduction of the VHL gene in CCRCC cells
      afforded resistance to VA's apoptotic effects. This resistance is mediated in
      part by the formation of stress granules that entrap signaling molecules that
      initiate the apoptotic signaling cascade. The VHL gene product was found to be a
      component of stress granules that develop as result of VA treatment. These
      findings reveal an important role for the VHL gene product in cytotoxic stress
      response and have important implications for the rational development of VA
      related compounds in chemotherapeutic targeting of CCRCC.

PMID- 22952427
TI  - Clinically relevant subsets identified by gene expression patterns support a
      revised ontogenic model of Wilms tumor: a Children's Oncology Group Study.
AB  - Wilms tumors (WT) have provided broad insights into the interface between
      development and tumorigenesis. Further understanding is confounded by their
      genetic, histologic, and clinical heterogeneity, the basis of which remains
      largely unknown. We evaluated 224 WT for global gene expression patterns; WT1,
      CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five
      subsets were identified showing distinct differences in their pathologic and
      clinical features: these findings were validated in 100 additional WT. The gene
      expression pattern of each subset was compared with published gene expression
      profiles during normal renal development. A novel subset of epithelial WT in
      infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed
      a gene expression pattern of the postinduction nephron, and none recurred. Three
      subsets were characterized by a low expression of WT1 and intralobar nephrogenic
      rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their
      age, in their relapse rate, and in their expression similarities with the
      intermediate mesoderm versus the metanephric mesenchyme. The largest subset was
      characterized by biallelic methylation of the imprint control region 1, a gene
      expression profile of the metanephric mesenchyme, and both interlunar and
      perilobar nephrogenic rests. These data provide a biologic explanation for the
      clinical and pathologic heterogeneity seen within WT and enable the future
      development of subset-specific therapeutic strategies. Further, these data
      support a revision of the current model of WT ontogeny, which allows for an
      interplay between the type of initiating event and the developmental stage in
      which it occurs.

PMID- 22952428
TI  - Plasmacytoid dendritic cells in the tumor microenvironment: immune targets for
      glioma therapeutics.
AB  - Adenovirus-mediated delivery of the immune-stimulatory cytokine Flt3L and the
      conditionally cytotoxic thymidine kinase (TK) induces tumor regression and long
      term survival in preclinical glioma (glioblastoma multiforme [GBM]) models. Flt3L
      induces expansion and recruitment of plasmacytoid dendritic cells (pDCs) into the
      brain. Although pDCs can present antigen and produce powerful inflammatory
      cytokines, that is, interferon alpha (IFN-alpha), their role in tumor immunology
      remains debated. Thus, we studied the role of pDCs and IFN-alpha in Ad.TK/GCV+
      Ad.Flt3L-mediated anti-GBM therapeutic efficacy. Our data indicate that the
      combined gene therapy induced recruitment of plasmacytoid DCs (pDCs) into the
      tumor mass; which were capable of in vivo phagocytosis, IFN-alpha release, and T
      cell priming. Thus, we next used either pDCs or an Ad vector encoding IFN-alpha
      delivered within the tumor microenvironment. When rats were treated with
      Ad.TK/GCV in combination with pDCs or Ad-IFN-alpha, they exhibited 35% and 50%
      survival, respectively. However, whereas intracranial administration of Ad.TK/GCV
      + Ad.Flt3L exhibited a high safety profile, Ad-IFN-alpha led to severe local
      inflammation, with neurologic and systemic adverse effects. To elucidate whether
      the efficacy of the immunotherapy was dependent on IFN-alpha-secreting pDCs, we
      administered an Ad vector encoding B18R, an IFN-alpha antagonist, which abrogated
      the antitumoral effect of Ad.TK/GCV + Ad.Flt3L. Our data suggest that IFN-alpha
      release by activated pDCs plays a critical role in the antitumor effect mediated
      by Ad.TK/GCV + Ad.Flt3L. In summary, taken together, our results demonstrate that
      pDCs mediate anti-GBM therapeutic efficacy through the production of IFN-alpha,
      thus manipulation of pDCs constitutes an attractive new therapeutic target for
      the treatment of GBM.

PMID- 22952430
TI  - Feature Identification of Compensatory Gene Pairs without Sequence Homology in
      Yeast.
AB  - Genetic robustness refers to a compensatory mechanism for buffering deleterious
      mutations or environmental variations. Gene duplication has been shown to provide
      such functional backups. However, the overall contribution of duplication-based
      buffering for genetic robustness is rather small. In this study, we investigated
      whether transcriptional compensation also exists among genes that share similar
      functions without sequence homology. A set of nonhomologous synthetic-lethal gene
      pairs was assessed by using a coexpression network, protein-protein interactions,
      and other types of genetic interactions in yeast. Our results are notably
      different from those of previous studies on buffering paralogs. The low
      expression similarity and the conditional coexpression alone do not play roles in
      identifying the functionally compensatory genes. Additional properties such as
      synthetic-lethal interaction, the ratio of shared common interacting partners,
      and the degree of coregulation were, at least in part, necessary to extract
      functional compensatory genes. Our network-based approach is applicable to select
      several well-documented cases of compensatory gene pairs and a set of new pairs.
      The results suggest that transcriptional reprogramming plays a limited role in
      functional compensation among nonhomologous genes. Our study aids in
      understanding the mechanism and features of functional compensation more in
      detail.

PMID- 22952431
TI  - An inordinate fondness for eukaryotic diversity.
AB  - Why do some groups of organisms, like beetles, have so many species, and others,
      like the tuataras, so few? This classic question in evolutionary biology has a
      deep history and has been studied using both fossils and phylogenetic trees.
      Phylogeny-based studies have focused on tree balance, which compares the number
      of species across clades of the same age in the tree. These studies have
      suggested that rates of speciation and extinction vary tremendously across the
      tree of life. In this issue, Rabosky et al. report the most ambitious study to
      date on the differences in species diversity across clades in the tree of life.
      The authors bring together a tremendously large dataset of multicellular
      eukaryotes, including all living species of plants, animals, and fungi; they
      divide these organisms into 1,397 clades, accounting for more than 1.2 million
      species in total. Rabosky et al. find tremendous variation in diversity across
      the tree of life. There are old clades with few species, young clades with many
      species, and everything in between. They also note a peculiar aspect of their
      data: it is difficult or impossible to predict how many species will be found in
      a particular clade knowing how long a clade has been diversifying from a common
      ancestor. This pattern suggests complex dynamics of speciation and extinction in
      the history of eukaryotes. Rabosky et al.'s paper represents the latest
      development in our efforts to understand the Earth's biodiversity at the broadest
      scales.

PMID- 22952432
TI  - How a blood cell intracellular signal keeps blood flowing.

PMID- 22952433
TI  - Child mortality estimation: estimating sex differences in childhood mortality
      since the 1970s.
AB  - INTRODUCTION: Producing estimates of infant (under age 1 y), child (age 1-4 y),
      and under-five (under age 5 y) mortality rates disaggregated by sex is
      complicated by problems with data quality and availability. Interpretation of sex
      differences requires nuanced analysis: girls have a biological advantage against
      many causes of death that may be eroded if they are disadvantaged in access to
      resources. Earlier studies found that girls in some regions were not experiencing
      the survival advantage expected at given levels of mortality. In this paper I
      generate new estimates of sex differences for the 1970s to the 2000s. METHODS AND
      FINDINGS: Simple fitting methods were applied to male-to-female ratios of infant
      and under-five mortality rates from vital registration, surveys, and censuses.
      The sex ratio estimates were used to disaggregate published series of both-sexes
      mortality rates that were based on a larger number of sources. In many developing
      countries, I found that sex ratios of mortality have changed in the same
      direction as historically occurred in developed countries, but typically had a
      lower degree of female advantage for a given level of mortality. Regional average
      sex ratios weighted by numbers of births were found to be highly influenced by
      China and India, the only countries where both infant mortality and overall under
      five mortality were estimated to be higher for girls than for boys in the 2000s.
      For the less developed regions (comprising Africa, Asia excluding Japan, Latin
      America/Caribbean, and Oceania excluding Australia and New Zealand), on average,
      boys' under-five mortality in the 2000s was about 2% higher than girls'. A number
      of countries were found to still experience higher mortality for girls than boys
      in the 1-4-y age group, with concentrations in southern Asia, northern
      Africa/western Asia, and western Africa. In the more developed regions
      (comprising Europe, northern America, Japan, Australia, and New Zealand), I found
      that the sex ratio of infant mortality peaked in the 1970s or 1980s and declined
      thereafter. CONCLUSIONS: The methods developed here pinpoint regions and
      countries where sex differences in mortality merit closer examination to ensure
      that both sexes are sharing equally in access to health resources. Further study
      of the distribution of causes of death in different settings will aid the
      interpretation of differences in survival for boys and girls. Please see later in
      the article for the Editors' Summary.

PMID- 22952434
TI  - Child mortality estimation: a comparison of UN IGME and IHME estimates of levels
      and trends in under-five mortality rates and deaths.
AB  - BACKGROUND: Millennium Development Goal 4 calls for a reduction in the under-five
      mortality rate (U5MR) by two-thirds between 1990 and 2015. In 2011, estimates
      were published by the United Nations Inter-agency Group for Child Mortality
      Estimation (UN IGME) and the Institute for Health Metrics and Evaluation (IHME).
      The difference in the U5MR estimates produced by the two research groups was more
      than 10% and corresponded to more than ten deaths per 1,000 live births for 10%
      of all countries in 1990 and 20% of all countries in 2010, which can lead to
      conflicting conclusions with respect to countries' progress. To understand what
      caused the differences in estimates, we summarised differences in underlying data
      and modelling approaches used by the two groups, and analysed their effects.
      METHODS AND FINDINGS: UN IGME and IHME estimation approaches differ with respect
      to the construction of databases and the pre-processing of data, trend fitting
      procedures, inclusion and exclusion of data series, and additional adjustment
      procedures. Large differences in U5MR estimates between the UN IGME and the IHME
      exist in countries with conflicts or civil unrest, countries with high HIV
      prevalence, and countries where the underlying data used to derive the estimates
      were different, especially if the exclusion of data series differed between the
      two research groups. A decomposition of the differences showed that differences
      in estimates due to using different data (inclusion of data series and pre
      processing of data) are on average larger than the differences due to using
      different trend fitting methods. CONCLUSIONS: Substantial country-specific
      differences between UN IGME and IHME estimates for U5MR and the number of under
      five deaths exist because of various differences in data and modelling
      assumptions used. Often differences are illustrative of the lack of reliable data
      and likely to decrease as more data become available. Improved transparency on
      methods and data used will help to improve understanding about the drivers of the
      differences. Please see later in the article for the Editors' Summary.

PMID- 22952435
TI  - Child mortality estimation: appropriate time periods for child mortality
      estimates from full birth histories.
AB  - BACKGROUND: Child mortality estimates from complete birth histories from
      Demographic and Health Surveys (DHS) surveys and similar surveys are a chief
      source of data used to track Millennium Development Goal 4, which aims for a
      reduction of under-five mortality by two-thirds between 1990 and 2015. Based on
      the expected sample sizes when the DHS program commenced, the estimates are
      usually based on 5-y time periods. Recent surveys have had larger sample sizes
      than early surveys, and here we aimed to explore the benefits of using shorter
      time periods than 5 y for estimation. We also explore the benefit of changing the
      estimation procedure from being based on years before the survey, i.e., measured
      with reference to the date of the interview for each woman, to being based on
      calendar years. METHODS AND FINDINGS: Jackknife variance estimation was used to
      calculate standard errors for 207 DHS surveys in order to explore to what extent
      the large samples in recent surveys can be used to produce estimates based on 1-,
      2-, 3-, 4-, and 5-y periods. We also recalculated the estimates for the surveys
      into calendar-year-based estimates. We demonstrate that estimation for 1-y
      periods is indeed possible for many recent surveys. CONCLUSIONS: The reduction in
      bias achieved using 1-y periods and calendar-year-based estimation is worthwhile
      in some cases. In particular, it allows tracking of the effects of particular
      events such as droughts, epidemics, or conflict on child mortality in a way not
      possible with previous estimation procedures. Recommendations to use estimation
      for short time periods when possible and to use calendar-year-based estimation
      were adopted in the United Nations 2011 estimates of child mortality.

PMID- 22952436
TI  - Child mortality estimation: consistency of under-five mortality rate estimates
      using full birth histories and summary birth histories.
AB  - BACKGROUND: Given the lack of complete vital registration data in most developing
      countries, for many countries it is not possible to accurately estimate under
      five mortality rates from vital registration systems. Heavy reliance is often
      placed on direct and indirect methods for analyzing data collected from birth
      histories to estimate under-five mortality rates. Yet few systematic comparisons
      of these methods have been undertaken. This paper investigates whether analysts
      should use both direct and indirect estimates from full birth histories, and
      under what circumstances indirect estimates derived from summary birth histories
      should be used. METHODS AND FINDINGS: Usings Demographic and Health Surveys data
      from West Africa, East Africa, Latin America, and South/Southeast Asia, I
      quantify the differences between direct and indirect estimates of under-five
      mortality rates, analyze data quality issues, note the relative effects of these
      issues, and test whether these issues explain the observed differences. I find
      that indirect estimates are generally consistent with direct estimates, after
      adjustment for fertility change and birth transference, but don't add substantial
      additional insight beyond direct estimates. However, choice of direct or indirect
      method was found to be important in terms of both the adjustment for data errors
      and the assumptions made about fertility. CONCLUSIONS: Although adjusted indirect
      estimates are generally consistent with adjusted direct estimates, some notable
      inconsistencies were observed for countries that had experienced either a
      political or economic crisis or stalled health transition in their recent past.
      This result suggests that when a population has experienced a smooth mortality
      decline or only short periods of excess mortality, both adjusted methods perform
      equally well. However, the observed inconsistencies identified suggest that the
      indirect method is particularly prone to bias resulting from violations of its
      strong assumptions about recent mortality and fertility. Hence, indirect
      estimates of under-five mortality rates from summary birth histories should be
      used only for populations that have experienced either smooth mortality declines
      or only short periods of excess mortality in their recent past. Please see later
      in the article for the Editors' Summary.

PMID- 22952437
TI  - Child mortality estimation: methods used to adjust for bias due to AIDS in
      estimating trends in under-five mortality.
AB  - In most low- and middle-income countries, child mortality is estimated from data
      provided by mothers concerning the survival of their children using methods that
      assume no correlation between the mortality risks of the mothers and those of
      their children. This assumption is not valid for populations with generalized HIV
      epidemics, however, and in this review, we show how the United Nations Inter
      agency Group for Child Mortality Estimation (UN IGME) uses a cohort component
      projection model to correct for AIDS-related biases in the data used to estimate
      trends in under-five mortality. In this model, births in a given year are
      identified as occurring to HIV-positive or HIV-negative mothers, the lives of the
      infants and mothers are projected forward using survivorship probabilities to
      estimate survivors at the time of a given survey, and the extent to which excess
      mortality of children goes unreported because of the deaths of HIV-infected
      mothers prior to the survey is calculated. Estimates from the survey for past
      periods can then be adjusted for the estimated bias. The extent of the AIDS
      related bias depends crucially on the dynamics of the HIV epidemic, on the length
      of time before the survey that the estimates are made for, and on the underlying
      non-AIDS child mortality. This simple methodology (which does not take into
      account the use of effective antiretroviral interventions) gives results
      qualitatively similar to those of other studies.

PMID- 22952438
TI  - Child mortality estimation: a global overview of infant and child mortality age
      patterns in light of new empirical data.
AB  - BACKGROUND: The under-five mortality rate (the probability of dying between birth
      and age 5 y, also denoted in the literature as U5MR and (5)q(0)) is a key
      indicator of child health, but it conceals important information about how this
      mortality is distributed by age. One important distinction is what amount of the
      under-five mortality occurs below age 1 y ((1)q(0)) versus at age 1 y and above
      ((4)q(1)). However, in many country settings, this distinction is often difficult
      to establish because of various types of data errors. As a result, it is common
      practice to resort to model age patterns to estimate (1)q(0) and (4)q(1) on the
      basis of an observed value of (5)q(0). The most commonly used model age patterns
      for this purpose are the Coale and Demeny and the United Nations systems. Since
      the development of these models, many additional sources of data for under-five
      mortality have become available, making possible a general evaluation of age
      patterns of infant and child mortality. In this paper, we do a systematic
      comparison of empirical values of (1)q(0) and (4)q(1) against model age patterns,
      and discuss whether observed deviations are due to data errors, or whether they
      reflect true epidemiological patterns not addressed in existing model life
      tables. METHODS AND FINDINGS: We used vital registration data from the Human
      Mortality Database, sample survey data from the World Fertility Survey and
      Demographic and Health Surveys programs, and data from Demographic Surveillance
      Systems. For each of these data sources, we compared empirical combinations of
      (1)q(0) and (4)q(1) against combinations provided by Coale and Demeny and United
      Nations model age patterns. We found that, on the whole, empirical values fall
      relatively well within the range provided by these models, but we also found
      important exceptions. Sub-Saharan African countries have a tendency to exhibit
      high values of (4)q(1) relative to (1)q(0), a pattern that appears to arise for
      the most part from true epidemiological causes. While this pattern is well known
      in the case of western Africa, we observed that it is more widespread than
      commonly thought. We also found that the emergence of HIV/AIDS, while perhaps
      contributing to high relative values of (4)q(1), does not appear to have
      substantially modified preexisting patterns. We also identified a small number of
      countries scattered in different parts of the world that exhibit unusually low
      values of (4)q(1) relative to (1)q(0), a pattern that is not likely to arise
      merely from data errors. Finally, we illustrate that it is relatively common for
      populations to experience changes in age patterns of infant and child mortality
      as they experience a decline in mortality. CONCLUSIONS: Existing models do not
      appear to cover the entire range of epidemiological situations and trajectories.
      Therefore, model life tables should be used with caution for estimating (1)q(0)
      and (4)q(1) on the basis of (5)q(0). Moreover, this model-based estimation
      procedure assumes that the input value of (5)q(0) is correct, which may not
      always be warranted, especially in the case of survey data. A systematic
      evaluation of data errors in sample surveys and their impact on age patterns of
      (1)q(0) and (4)q(1) is urgently needed, along with the development of model age
      patterns of under-five mortality that would cover a wider range of
      epidemiological situations and trajectories. Please see later in the article for
      the Editors' Summary.

PMID- 22952440
TI  - What is the relationship of medical humanitarian organisations with mining and
      other extractive industries?
AB  - Philippe Calain discusses the health and environmental hazards of extractive
      industries like mining and explores the tensions that arise when medical
      humanitarian organizations are called to intervene in emergencies involving the
      extractive sector.

PMID- 22952441
TI  - Child mortality estimation: accelerated progress in reducing global child
      mortality, 1990-2010.
AB  - Monitoring development indicators has become a central interest of international
      agencies and countries for tracking progress towards the Millennium Development
      Goals. In this review, which also provides an introduction to a collection of
      articles, we describe the methodology used by the United Nations Inter-agency
      Group for Child Mortality Estimation to track country-specific changes in the key
      indicator for Millennium Development Goal 4 (MDG 4), the decline of the under
      five mortality rate (the probability of dying between birth and age five, also
      denoted in the literature as U5MR and (5)q(0)). We review how relevant data from
      civil registration, sample registration, population censuses, and household
      surveys are compiled and assessed for United Nations member states, and how time
      series regression models are fitted to all points of acceptable quality to
      establish the trends in U5MR from which infant and neonatal mortality rates are
      generally derived. The application of this methodology indicates that, between
      1990 and 2010, the global U5MR fell from 88 to 57 deaths per 1,000 live births,
      and the annual number of under-five deaths fell from 12.0 to 7.6 million.
      Although the annual rate of reduction in the U5MR accelerated from 1.9% for the
      period 1990-2000 to 2.5% for the period 2000-2010, it remains well below the 4.4%
      annual rate of reduction required to achieve the MDG 4 goal of a two-thirds
      reduction in U5MR from its 1990 value by 2015. Thus, despite progress in reducing
      child mortality worldwide, and an encouraging increase in the pace of decline
      over the last two decades, MDG 4 will not be met without greatly increasing
      efforts to reduce child deaths.

PMID- 22952439
TI  - Multidrug resistant pulmonary tuberculosis treatment regimens and patient
      outcomes: an individual patient data meta-analysis of 9,153 patients.
AB  - BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy,
      toxic, expensive, and has generally poor outcomes. We undertook an individual
      patient data meta-analysis to assess the impact on outcomes of the type, number,
      and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent
      systematic reviews were used to identify studies reporting treatment outcomes of
      microbiologically confirmed MDR-TB. Study authors were contacted to solicit
      individual patient data including clinical characteristics, treatment given, and
      outcomes. Random effects multivariable logistic meta-regression was used to
      estimate adjusted odds of treatment success. Adequate treatment and outcome data
      were provided for 9,153 patients with MDR-TB from 32 observational studies.
      Treatment success, compared to failure/relapse, was associated with use of: later
      generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]),
      ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3
      2.3]), use of four or more likely effective drugs in the initial intensive phase
      (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the
      continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the
      association of treatment success compared to failure/relapse or death: later
      generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]),
      ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely
      effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or
      more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).
      CONCLUSIONS: In this individual patient data meta-analysis of observational data,
      improved MDR-TB treatment success and survival were associated with use of
      certain fluoroquinolones, ethionamide, or prothionamide, and greater total number
      of effective drugs. However, randomized trials are urgently needed to optimize
      MDR-TB treatment. Please see later in the article for the Editors' Summary.

PMID- 22952442
TI  - Versatility and invariance in the evolution of homologous heteromeric interfaces.
AB  - Evolutionary pressures act on protein complex interfaces so that they preserve
      their complementarity. Nonetheless, the elementary interactions which compose the
      interface are highly versatile throughout evolution. Understanding and
      characterizing interface plasticity across evolution is a fundamental issue which
      could provide new insights into protein-protein interaction prediction. Using a
      database of 1,024 couples of close and remote heteromeric structural interologs,
      we studied protein-protein interactions from a structural and evolutionary point
      of view. We systematically and quantitatively analyzed the conservation of
      different types of interface contacts. Our study highlights astonishing
      plasticity regarding polar contacts at complex interfaces. It also reveals that
      up to a quarter of the residues switch out of the interface when comparing two
      homologous complexes. Despite such versatility, we identify two important
      interface descriptors which correlate with an increased conservation in the
      evolution of interfaces: apolar patches and contacts surrounding anchor residues.
      These observations hold true even when restricting the dataset to transiently
      formed complexes. We show that a combination of six features related either to
      sequence or to geometric properties of interfaces can be used to rank positions
      likely to share similar contacts between two interologs. Altogether, our analysis
      provides important tracks for extracting meaningful information from multiple
      sequence alignments of conserved binding partners and for discriminating near
      native interfaces using evolutionary information.

PMID- 22952443
TI  - The roots of bioinformatics in ISMB.

PMID- 22952444
TI  - Bacterial cell surface heterogeneity: a pathogen's disguise.

PMID- 22952445
TI  - Inhibition of Candida parapsilosis fatty acid synthase (Fas2) induces
      mitochondrial cell death in serum.
AB  - We have recently observed that a fatty acid auxotrophic mutant (fatty acid
      synthase, Fas2Delta/Delta) of the emerging human pathogenic yeast Candida
      parapsilosis dies after incubation in various media including serum. In the
      present study we describe the mechanism for cell death induced by serum and
      glucose containing media. We show that Fas2Delta/Delta yeast cells are profoundly
      susceptible to glucose leading us to propose that yeast cells lacking fatty acids
      exhibit uncontrolled metabolism in response to glucose. We demonstrate that
      incubation of Fas2Delta/Delta yeast cells with serum leads to cell death, and
      this process can be prevented with inhibition of protein or DNA synthesis,
      indicating that newly synthesized cellular components are detrimental to the
      mutant cells. Furthermore, we have found that cell death is mediated by
      mitochondria. Suppression of electron transport enzymes using inhibitors such as
      cyanide or azide prevents ROS overproduction and Fas2Delta/Delta yeast cell
      death. Additionally, deletion of mitochondrial DNA, which encodes several
      subunits for enzymes of the electron transport chain, significantly reduces serum
      induced Fas2Delta/Delta yeast cell death. Therefore, our results show that serum
      and glucose media induce Fas2Delta/Delta yeast cell death by triggering
      unbalanced metabolism, which is regulated by mitochondria. To our knowledge, this
      is the first study to critically define a link between cytosolic fatty acid
      synthesis and mitochondrial function in response to serum stress in C.
      parapsilosis.

PMID- 22952446
TI  - Measles immune suppression: lessons from the macaque model.
AB  - Measles remains a significant childhood disease, and is associated with a
      transient immune suppression. Paradoxically, measles virus (MV) infection also
      induces robust MV-specific immune responses. Current hypotheses for the mechanism
      underlying measles immune suppression focus on functional impairment of
      lymphocytes or antigen-presenting cells, caused by infection with or exposure to
      MV. We have generated stable recombinant MVs that express enhanced green
      fluorescent protein, and remain virulent in non-human primates. By performing a
      comprehensive study of virological, immunological, hematological and
      histopathological observations made in animals euthanized at different time
      points after MV infection, we developed a model explaining measles immune
      suppression which fits with the "measles paradox". Here we show that MV
      preferentially infects CD45RA(-) memory T-lymphocytes and follicular B
      lymphocytes, resulting in high infection levels in these populations. After the
      peak of viremia MV-infected lymphocytes were cleared within days, followed by
      immune activation and lymph node enlargement. During this period tuberculin
      specific T-lymphocyte responses disappeared, whilst strong MV-specific T
      lymphocyte responses emerged. Histopathological analysis of lymphoid tissues
      showed lymphocyte depletion in the B- and T-cell areas in the absence of
      apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell
      follicles and reappearance of proliferating cells. Our findings indicate an
      immune-mediated clearance of MV-infected CD45RA(-) memory T-lymphocytes and
      follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid
      oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this
      depletion, explaining the short duration of measles lymphopenia yet long duration
      of immune suppression.

PMID- 22952447
TI  - Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in
      chimpanzees.
AB  - Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and
      there is an urgent need to develop therapies to reduce rates of HCV infection of
      transplanted livers. Approved therapeutics for HCV are poorly tolerated and are
      of limited efficacy in this patient population. Human monoclonal antibody HCV1
      recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein
      (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a
      chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to
      infusion with genotype 1a H77 HCV provided complete protection from HCV
      infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an
      acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to
      virus had a rapid reduction in viral load to below the limit of detection before
      rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D)
      conferring resistance to HCV1 neutralization. Finally, three chronically HCV
      infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral
      load was reduced to below the limit of detection for 21 days in one chimpanzee
      with rebounding virus displaying a resistance mutation (N417S). The other two
      chimpanzees had 0.5-1.0 log(10) reductions in viral load without evidence of
      viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp)
      demonstrated that the sera from the poorly-responding chimpanzees inhibited the
      ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the
      chronically-infected chimpanzees implicated endogenous antibody to E2 and
      interference with HCV1 neutralization although other factors may also be
      responsible. These data suggest that human monoclonal antibody HCV1 may be an
      effective therapeutic for the prevention of graft infection in HCV-infected
      patients undergoing liver transplantation.

PMID- 22952448
TI  - Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus
      infection.
AB  - BK polyomavirus (BKPyV) is an emerging pathogen whose reactivation causes severe
      disease in transplant patients. Unfortunately, there is no specific anti-BKPyV
      treatment available, and host cell components that affect the infection outcome
      are not well characterized. In this report, we examined the relationship between
      BKPyV productive infection and the activation of the cellular DNA damage response
      (DDR) in natural host cells. Our results showed that both the ataxia
      telangiectasia mutated (ATM)- and ATM and Rad-3-related (ATR)-mediated DDR were
      activated during BKPyV infection, accompanied by the accumulation of polyploid
      cells. We assessed the involvement of ATM and ATR during infection using small
      interfering RNA (siRNA) knockdowns. ATM knockdown did not significantly affect
      viral gene expression, but reduced BKPyV DNA replication and infectious progeny
      production. ATR knockdown had a slightly more dramatic effect on viral T antigen
      (TAg) and its modified forms, DNA replication, and progeny production. ATM and
      ATR double knockdown had an additive effect on DNA replication and resulted in a
      severe reduction in viral titer. While ATM mainly led to the activation of pChk2
      and ATR was primarily responsible for the activation of pChk1, knockdown of all
      three major phosphatidylinositol 3-kinase-like kinases (ATM, ATR, and DNA-PKcs)
      did not abolish the activation of gammaH2AX during BKPyV infection. Finally, in
      the absence of ATM or ATR, BKPyV infection caused severe DNA damage and aberrant
      TAg staining patterns. These results indicate that induction of the DDR by BKPyV
      is critical for productive infection, and that one of the functions of the DDR is
      to minimize the DNA damage which is generated during BKPyV infection.

PMID- 22952449
TI  - Telomere length affects the frequency and mechanism of antigenic variation in
      Trypanosoma brucei.
AB  - Trypanosoma brucei is a master of antigenic variation and immune response
      evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface
      Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by
      "switching" from the expression of one VSG to another. Each active VSG is
      monoallelically expressed from only one of approximately 15 subtelomeric sites.
      Switching VSG expression occurs by three predominant mechanisms, arguably the
      most significant of which is the non-reciprocal exchange of VSG containing DNA by
      duplicative gene conversion (GC). How T. brucei orchestrates its complex
      switching mechanisms remains to be elucidated. Recent work has demonstrated that
      an exogenous DNA break in the active site could initiate a GC based switch, yet
      the source of the switch-initiating DNA lesion under natural conditions is still
      unknown. Here we investigated the hypothesis that telomere length directly
      affects VSG switching. We demonstrate that telomerase deficient strains with
      short telomeres switch more frequently than genetically identical strains with
      long telomeres and that, when the telomere is short, switching preferentially
      occurs by GC. Our data supports the hypothesis that a short telomere at the
      active VSG expression site results in an increase in subtelomeric DNA breaks,
      which can initiate GC based switching. In addition to their significance for T.
      brucei and telomere biology, the findings presented here have implications for
      the many diverse pathogens that organize their antigenic genes in subtelomeric
      regions.

PMID- 22952450
TI  - Ablation of the regulatory IE1 protein of murine cytomegalovirus alters in vivo
      pro-inflammatory TNF-alpha production during acute infection.
AB  - Little is known about the role of viral genes in modulating host cytokine
      responses. Here we report a new functional role of the viral encoded IE1 protein
      of the murine cytomegalovirus in sculpting the inflammatory response in an acute
      infection. In time course experiments of infected primary macrophages (MPhis)
      measuring cytokine production levels, genetic ablation of the immediate-early 1
      (ie1) gene results in a significant increase in TNFalpha production.
      Intracellular staining for cytokine production and viral early gene expression
      shows that TNFalpha production is highly associated with the productively
      infected MPhi population of cells. The ie1- dependent phenotype of enhanced MPhi
      TNFalpha production occurs at both protein and RNA levels. Noticeably, we show in
      a series of in vivo infection experiments that in multiple organs the presence of
      ie1 potently inhibits the pro-inflammatory cytokine response. From these
      experiments, levels of TNFalpha, and to a lesser extent IFNbeta, but not the anti
      inflammatory cytokine IL10, are moderated in the presence of ie1. The ie1-
      mediated inhibition of TNFalpha production has a similar quantitative phenotype
      profile in infection of susceptible (BALB/c) and resistant (C57BL/6) mouse
      strains as well as in a severe immuno-ablative model of infection. In vitro
      experiments with infected macrophages reveal that deletion of ie1 results in
      increased sensitivity of viral replication to TNFalpha inhibition. However, in
      vivo infection studies show that genetic ablation of TNFalpha or TNFRp55 receptor
      is not sufficient to rescue the restricted replication phenotype of the ie1
      mutant virus. These results provide, for the first time, evidence for a role of
      IE1 as a regulator of the pro-inflammatory response and demonstrate a specific
      pathogen gene capable of moderating the host production of TNFalpha in vivo.

PMID- 22952451
TI  - Reprogramming to pluripotency can conceal somatic cell chromosomal instability.
AB  - The discovery that somatic cells are reprogrammable to pluripotency by ectopic
      expression of a small subset of transcription factors has created great potential
      for the development of broadly applicable stem-cell-based therapies. One of the
      concerns regarding the safe use of induced pluripotent stem cells (iPSCs) in
      therapeutic applications is loss of genomic integrity, a hallmark of various
      human conditions and diseases, including cancer. Structural chromosome defects
      such as short telomeres and double-strand breaks are known to limit reprogramming
      of somatic cells into iPSCs, but whether defects that cause whole-chromosome
      instability (W-CIN) preclude reprogramming is unknown. Here we demonstrate, using
      aneuploidy-prone mouse embryonic fibroblasts (MEFs) in which chromosome
      missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a
      barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting
      effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively
      yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal
      iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically
      unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These
      findings suggest that aneuploid cells can be selected for or against during
      reprogramming depending on the W-CIN gene defect and present the novel concept
      that somatic cell W-CIN can be concealed in the pluripotent state. Thus,
      karyotypic analysis of somatic cells of origin in addition to iPSC lines is
      necessary for safe application of reprogramming technology.

PMID- 22952452
TI  - Loss of axonal mitochondria promotes tau-mediated neurodegeneration and
      Alzheimer's disease-related tau phosphorylation via PAR-1.
AB  - Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are
      involved in the pathogenesis of Alzheimer's disease (AD); however, what
      pathological conditions trigger tau abnormality in AD is not fully understood. A
      reduction in the number of mitochondria in the axon has been implicated in AD. In
      this study, we investigated whether and how loss of axonal mitochondria promotes
      tau phosphorylation and toxicity in vivo. Using transgenic Drosophila expressing
      human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor
      protein essential for axonal transport of mitochondria, enhanced human tau
      induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262
      increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1),
      the Drosophila homolog of mammalian microtubule affinity-regulating kinase,
      mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has
      been reported to promote tau detachment from microtubules, and we found that the
      levels of microtubule-unbound free tau increased by milton knockdown. Blocking
      tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262
      site to unphosphorylatable alanine suppressed the enhancement of tau-induced
      neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or
      Miro increased the levels of active PAR-1. These results suggest that an increase
      in tau phosphorylation at Ser262 through PAR-1 contributes to tau-mediated
      neurodegeneration under a pathological condition in which axonal mitochondria is
      depleted. Intriguingly, we found that knockdown of milton or Miro alone caused
      late-onset neurodegeneration in the fly brain, and this neurodegeneration could
      be suppressed by knockdown of Drosophila tau or PAR-1. Our results suggest that
      loss of axonal mitochondria may play an important role in tau phosphorylation and
      toxicity in the pathogenesis of AD.

PMID- 22952453
TI  - Ccdc94 protects cells from ionizing radiation by inhibiting the expression of
      p53.
AB  - DNA double-strand breaks (DSBs) represent one of the most deleterious forms of
      DNA damage to a cell. In cancer therapy, induction of cell death by DNA DSBs by
      ionizing radiation (IR) and certain chemotherapies is thought to mediate the
      successful elimination of cancer cells. However, cancer cells often evolve to
      evade the cytotoxicity induced by DNA DSBs, thereby forming the basis for
      treatment resistance. As such, a better understanding of the DSB DNA damage
      response (DSB-DDR) pathway will facilitate the design of more effective
      strategies to overcome chemo- and radioresistance. To identify novel mechanisms
      that protect cells from the cytotoxic effects of DNA DSBs, we performed a forward
      genetic screen in zebrafish for recessive mutations that enhance the IR-induced
      apoptotic response. Here, we describe radiosensitizing mutation 7 (rs7), which
      causes a severe sensitivity of zebrafish embryonic neurons to IR-induced
      apoptosis and is required for the proper development of the central nervous
      system. The rs7 mutation disrupts the coding sequence of ccdc94, a highly
      conserved gene that has no previous links to the DSB-DDR pathway. We demonstrate
      that Ccdc94 is a functional member of the Prp19 complex and that genetic
      knockdown of core members of this complex causes increased sensitivity to IR
      induced apoptosis. We further show that Ccdc94 and the Prp19 complex protect
      cells from IR-induced apoptosis by repressing the expression of p53 mRNA. In
      summary, we have identified a new gene regulating a dosage-sensitive response to
      DNA DSBs during embryonic development. Future studies in human cancer cells will
      determine whether pharmacological inactivation of CCDC94 reduces the threshold of
      the cancer cell apoptotic response.

PMID- 22952454
TI  - Phylogenetic and transcriptomic analysis of chemosensory receptors in a pair of
      divergent ant species reveals sex-specific signatures of odor coding.
AB  - Ants are a highly successful family of insects that thrive in a variety of
      habitats across the world. Perhaps their best-known features are complex social
      organization and strict division of labor, separating reproduction from the day
      to-day maintenance and care of the colony, as well as strict discrimination
      against foreign individuals. Since these social characteristics in ants are
      thought to be mediated by semiochemicals, a thorough analysis of these signals,
      and the receptors that detect them, is critical in revealing mechanisms that lead
      to stereotypic behaviors. To address these questions, we have defined and
      characterized the major chemoreceptor families in a pair of behaviorally and
      evolutionarily distinct ant species, Camponotus floridanus and Harpegnathos
      saltator. Through comprehensive re-annotation, we show that these ant species
      harbor some of the largest yet known repertoires of odorant receptors (Ors) among
      insects, as well as a more modest number of gustatory receptors (Grs) and variant
      ionotropic glutamate receptors (Irs). Our phylogenetic analyses further
      demonstrate remarkably rapid gains and losses of ant Ors, while Grs and Irs have
      also experienced birth-and-death evolution to different degrees. In addition,
      comparisons of antennal transcriptomes between sexes identify many chemoreceptors
      that are differentially expressed between males and females and between species.
      We have also revealed an agonist for a worker-enriched OR from C. floridanus,
      representing the first case of a heterologously characterized ant tuning Or.
      Collectively, our analysis reveals a large number of ant chemoreceptors
      exhibiting patterns of differential expression and evolution consistent with
      sex/species-specific functions. These differentially expressed genes are likely
      associated with sex-based differences, as well as the radically different social
      lifestyles observed between C. floridanus and H. saltator, and thus are targets
      for further functional characterization. Our findings represent an important
      advance toward understanding the molecular basis of social interactions and the
      differential chemical ecologies among ant species.

PMID- 22952455
TI  - Combining comparative proteomics and molecular genetics uncovers regulators of
      synaptic and axonal stability and degeneration in vivo.
AB  - Degeneration of synaptic and axonal compartments of neurons is an early event
      contributing to the pathogenesis of many neurodegenerative diseases, but the
      underlying molecular mechanisms remain unclear. Here, we demonstrate the
      effectiveness of a novel "top-down" approach for identifying proteins and
      functional pathways regulating neurodegeneration in distal compartments of
      neurons. A series of comparative quantitative proteomic screens on synapse
      enriched fractions isolated from the mouse brain following injury identified
      dynamic perturbations occurring within the proteome during both initiation and
      onset phases of degeneration. In silico analyses highlighted significant
      clustering of proteins contributing to functional pathways regulating synaptic
      transmission and neurite development. Molecular markers of degeneration were
      conserved in injury and disease, with comparable responses observed in synapse
      enriched fractions isolated from mouse models of Huntington's disease (HD) and
      spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration
      associated proteins using mutant Drosophila lines revealed six potential
      regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2,
      ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration.
      Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of
      distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants
      confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying
      degeneration in axonal and synaptic compartments. Our study has identified
      conserved molecular responses occurring within synapse-enriched fractions of the
      mouse brain during the early stages of neurodegeneration, focused on functional
      networks modulating synaptic transmission and incorporating molecular chaperones,
      cytoskeletal modifiers, and calcium-binding proteins. We propose that the
      proteins and functional pathways identified in the current study represent
      attractive targets for developing therapeutics aimed at modulating synaptic and
      axonal stability and neurodegeneration in vivo.

PMID- 22952456
TI  - Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency
      associated developmental defects by preventing matriptase activation.
AB  - Loss of either hepatocyte growth factor activator inhibitor (HAI)-1 or -2 is
      associated with embryonic lethality in mice, which can be rescued by the
      simultaneous inactivation of the membrane-anchored serine protease, matriptase,
      thereby demonstrating that a matriptase-dependent proteolytic pathway is a
      critical developmental target for both protease inhibitors. Here, we performed a
      genetic epistasis analysis to identify additional components of this pathway by
      generating mice with combined deficiency in either HAI-1 or HAI-2, along with
      genes encoding developmentally co-expressed candidate matriptase targets, and
      screening for the rescue of embryonic development. Hypomorphic mutations in
      Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8),
      restored placentation and normal development of HAI-1-deficient embryos and
      prevented early embryonic lethality, mid-gestation lethality due to placental
      labyrinth failure, and neural tube defects in HAI-2-deficient embryos.
      Inactivation of genes encoding c-Met, protease-activated receptor-2 (PAR-2), or
      the epithelial sodium channel (ENaC) alpha subunit all failed to rescue embryonic
      lethality, suggesting that deregulated matriptase-prostasin activity causes
      developmental failure independent of aberrant c-Met and PAR-2 signaling or
      impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1
      and matriptase double-deficient embryos suggests that the protease may not be
      critical for focal proteolytic activation of PAR-2 during neural tube closure.
      Paradoxically, although matriptase auto-activates and is a well-established
      upstream epidermal activator of prostasin, biochemical analysis of matriptase-
      and prostasin-deficient placental tissues revealed a requirement of prostasin for
      conversion of the matriptase zymogen to active matriptase, whereas prostasin
      zymogen activation was matriptase-independent.

PMID- 22952457
TI  - Blood selenium levels and contribution of food groups to selenium intake in
      adolescent girls in Iceland.
AB  - BACKGROUND/OBJECTIVES: Significant changes have been reported in dietary habits
      and food availability in Iceland that would be expected to compromise selenium
      intake and status, especially among young people. These include substantial
      decreases in the consumption of fish and milk, as well as the selenium content of
      imported wheat. The aim of this study was to assess selenium in the diet and
      whole blood of adolescent girls, as well as define the most important foods
      contributing to intake and blood concentrations of selenium. DESIGN: The subjects
      were 96 randomly selected girls, aged 16-20, who answered a validated food
      frequency questionnaire (FFQ) for dietary assessment. Selenium intake from each
      food group was calculated in ug/day. Blood samples were collected for measurement
      of whole blood selenium. RESULTS: Mean dietary selenium was 51+/-25 ug/day.
      Milk/dairy products, including cheese, contributed 36+/-14% of total dietary
      selenium; fish 18+/-12%; and bread/cereal products 13+/-6%. Mean whole blood
      selenium was 117+/-12 ug/l (range 90-208); nearly 90% of subjects were above the
      optimal level of 100 ug/l. Fish and bread/cereal products were the only foods
      significantly correlated with selenium in blood (r=0.32; P=0.002 and r=0.22;
      P=0.04, respectively) while no correlation was found with milk and dairy products
      in spite of their greater contribution to total selenium intake. CONCLUSION: In
      this population of Icelandic adolescent girls, selenium intake and status seem
      acceptable. Judging from associations between intake and blood levels, fish and
      cereals may be the most important contributors to blood selenium.

PMID- 22952458
TI  - Locomotor sensitization to EtOH: contribution of beta-Endorphin.
AB  - Alcohol use disorders, like all drug addictions, involve a constellation of
      adaptive changes throughout the brain. Neural activity underlying changes in the
      rewarding properties of alcohol reflect changes in dopamine transmission in
      mesolimbic and nigrostriatal pathways and these effects are modulated by
      endogenous opioids such as beta-Endorphin. In order to study the role of beta
      Endorphin in the development of locomotor sensitization to repeated EtOH
      exposure, we tested transgenic mice that vary in their capacity to synthesize
      this peptide as a result of constitutive modification of the Pomc gene. Our
      results indicate that mice deficient in beta-Endorphin show attenuated locomotor
      activation following an acute injection of EtOH (2.0 g/kg) and, in contrast to
      wildtype mice, fail to demonstrate locomotor sensitization after 12 days of
      repeated EtOH injections. These data support the idea that beta-Endorphin
      modulates the locomotor effects of EtOH and contributes to the neuroadaptive
      changes associated with chronic use.

PMID- 22952460
TI  - Focused attention vs. crossmodal signals paradigm: deriving predictions from the
      time-window-of-integration model.
AB  - In the crossmodal signals paradigm (CSP) participants are instructed to respond
      to a set of stimuli from different modalities, presented more or less
      simultaneously, as soon as a stimulus from any modality has been detected. In the
      focused attention paradigm (FAP), on the other hand, responses should only be
      made to a stimulus from a pre-defined target modality and stimuli from non-target
      modalities should be ignored. Whichever paradigm is being applied, a typical
      result is that responses tend to be faster to crossmodal stimuli than to unimodal
      stimuli, a phenomenon often referred to as "crossmodal interaction." Here, we
      investigate predictions of the time-window-of-integration (TWIN) modeling
      framework previously proposed by the authors. It is shown that TWIN makes
      specific qualitative and quantitative predictions on how the two paradigms differ
      with respect to the probability of multisensory integration and the amount of
      response enhancement, including the effect of stimulus intensity ("inverse
      effectiveness"). Introducing a decision-theoretic framework for TWIN further
      allows comparing the two paradigms with respect to the predicted optimal time
      window size and its dependence on the prior probability that the crossmodal
      stimulus information refers to the same event. In order to test these
      predictions, experimental studies that systematically compare crossmodal effects
      under stimulus conditions that are identical except for the CSP-FAP instruction
      should be performed in the future.

PMID- 22952461
TI  - Testing the attentional boundary conditions of subliminal semantic priming: the
      influence of semantic and phonological task sets.
AB  - Recent studies challenged the classical notion of automaticity and indicated that
      even unconscious automatic semantic processing is under attentional control to
      some extent. In line with our attentional sensitization model, these data suggest
      that a sensitization of semantic pathways by a semantic task set is necessary for
      subliminal semantic priming to occur while non-semantic task sets attenuate
      priming. In the present study, we tested whether masked semantic priming is also
      reduced by phonological task sets using the previously developed induction task
      paradigm. This would substantiate the notion that attention to semantics is
      necessary for eliciting unconscious semantic priming. Participants first
      performed semantic and phonological induction tasks that should either activate a
      semantic or a phonological task set. Subsequent to the induction task, a masked
      prime word, either associated or non-associated with the following lexical
      decision target word, was presented. Across two experiments, we varied the nature
      of the phonological induction task (word phonology vs. letter phonology) to
      assess whether the attentional focus on the entire word vs. single letters
      modulates subsequent masked semantic priming. In both experiments, subliminal
      semantic priming was only found subsequent to the semantic induction task, but
      was attenuated following either phonological induction task. These results
      indicate that attention to phonology attenuates subsequent semantic processing of
      unconsciously presented primes whether or not attention is directed to the entire
      word or to single letters. The present findings therefore substantiate earlier
      evidence that an attentional orientation toward semantics is necessary for
      subliminal semantic priming to be elicited.

PMID- 22952459
TI  - Connectivity-based structural and functional parcellation of the human cortex
      using diffusion imaging and tractography.
AB  - The parcellation of the cortex via its anatomical properties has been an
      important research endeavor for over a century. To date, however, a universally
      accepted parcellation scheme for the human brain still remains elusive. In the
      current review, we explore the use of in vivo diffusion imaging and white matter
      tractography as a non-invasive method for the structural and functional
      parcellation of the human cerebral cortex, discussing the strengths and
      limitations of the current approaches. Cortical parcellation via white matter
      connectivity is based on the premise that, as connectional anatomy determines
      functional organization, it should be possible to segregate functionally-distinct
      cortical regions by identifying similarities and differences in connectivity
      profiles. Recent studies have provided initial evidence in support of the
      efficacy of this connectional parcellation methodology. Such investigations have
      identified distinct cortical subregions which correlate strongly with functional
      regions identified via fMRI and meta-analyses. Furthermore, a strong parallel
      between the cortical regions defined via tractographic and more traditional
      cytoarchitectonic parcellation methods has been observed. However, the degree of
      correspondence and relative functional importance of cytoarchitectonic- versus
      connectivity-derived parcellations still remains unclear. Diffusion tractography
      remains one of the only methods capable of visualizing the structural networks of
      the brain in vivo. As such, it is of vital importance to continue to improve the
      accuracy of the methodology and to extend its potential applications in the study
      of cognition in neurological health and disease.

PMID- 22952462
TI  - Astroglial networks and implications for therapeutic neuromodulation of epilepsy.
AB  - Epilepsy is a common chronic neurologic disorder affecting approximately 1% of
      the world population. More than one-third of all epilepsy patients have
      incompletely controlled seizures or debilitating medication side effects in spite
      of optimal medical management. Medically refractory epilepsy is associated with
      excess injury and mortality, psychosocial dysfunction, and significant cognitive
      impairment. Effective treatment options for these patients can be limited. The
      cellular mechanisms underlying seizure activity are incompletely understood,
      though we here describe multiple lines of evidence supporting the likely
      contribution of astroglia to epilepsy, with focus on individual astrocytes and
      their network functions. Of the emerging therapeutic modalities for epilepsy, one
      of the most intriguing is the field of neuromodulation. Neuromodulatory
      treatment, which consists of administering electrical pulses to neural tissue to
      modulate its activity leading to a beneficial effect, may be an option for these
      patients. Current modalities consist of vagal nerve stimulation, open and closed
      loop stimulation, and transcranial magnetic stimulation. Due to their unique
      properties, we here present astrocytes as likely important targets for the
      developing field of neuromodulation in the treatment of epilepsy.

PMID- 22952464
TI  - Critical fluctuations in cortical models near instability.
AB  - Computational studies often proceed from the premise that cortical dynamics
      operate in a linearly stable domain, where fluctuations dissipate quickly and
      show only short memory. Studies of human electroencephalography (EEG), however,
      have shown significant autocorrelation at time lags on the scale of minutes,
      indicating the need to consider regimes where non-linearities influence the
      dynamics. Statistical properties such as increased autocorrelation length,
      increased variance, power law scaling, and bistable switching have been suggested
      as generic indicators of the approach to bifurcation in non-linear dynamical
      systems. We study temporal fluctuations in a widely-employed computational model
      (the Jansen-Rit model) of cortical activity, examining the statistical signatures
      that accompany bifurcations. Approaching supercritical Hopf bifurcations through
      tuning of the background excitatory input, we find a dramatic increase in the
      autocorrelation length that depends sensitively on the direction in phase space
      of the input fluctuations and hence on which neuronal subpopulation is
      stochastically perturbed. Similar dependence on the input direction is found in
      the distribution of fluctuation size and duration, which show power law scaling
      that extends over four orders of magnitude at the Hopf bifurcation. We conjecture
      that the alignment in phase space between the input noise vector and the center
      manifold of the Hopf bifurcation is directly linked to these changes. These
      results are consistent with the possibility of statistical indicators of linear
      instability being detectable in real EEG time series. However, even in a simple
      cortical model, we find that these indicators may not necessarily be visible even
      when bifurcations are present because their expression can depend sensitively on
      the neuronal pathway of incoming fluctuations.

PMID- 22952463
TI  - Local amplification of glucocorticoids in the aging brain and impaired spatial
      memory.
AB  - The hippocampus is a prime target for glucocorticoids (GCs) and a brain structure
      particularly vulnerable to aging. Prolonged exposure to excess GCs compromises
      hippocampal electrophysiology, structure, and function. Blood GC levels tend to
      increase with aging and correlate with impaired spatial memory in aging rodents
      and humans. The magnitude of GC action within tissues depends not only on levels
      of steroid hormone that enter the cells from the periphery and the density of
      intracellular receptors but also on the local metabolism of GCs by 11beta
      hydroxysteroid dehydrogenases (11beta-HSD). The predominant isozyme in the adult
      brain, 11beta-HSD1, locally regenerates active GCs from inert 11-keto forms thus
      amplifying GC levels within specific target cells including in the hippocampus
      and cortex. Aging associates with elevated hippocampal and neocortical 11beta
      HSD1 and impaired spatial learning while deficiency of 11beta-HSD1 in knockout
      (KO) mice prevents the emergence of cognitive decline with age. Furthermore,
      short-term pharmacological inhibition of 11beta-HSD1 in already aged mice
      reverses spatial memory impairments. Here, we review research findings that
      support a key role for GCs with special emphasis on their intracellular
      regulation by 11beta-HSD1 in the emergence of spatial memory deficits with aging,
      and discuss the use of 11beta-HSD1 inhibitors as a promising novel treatment in
      ameliorating/improving age-related memory impairments.

PMID- 22952465
TI  - Statistical conclusion validity: some common threats and simple remedies.
AB  - The ultimate goal of research is to produce dependable knowledge or to provide
      the evidence that may guide practical decisions. Statistical conclusion validity
      (SCV) holds when the conclusions of a research study are founded on an adequate
      analysis of the data, generally meaning that adequate statistical methods are
      used whose small-sample behavior is accurate, besides being logically capable of
      providing an answer to the research question. Compared to the three other
      traditional aspects of research validity (external validity, internal validity,
      and construct validity), interest in SCV has recently grown on evidence that
      inadequate data analyses are sometimes carried out which yield conclusions that a
      proper analysis of the data would not have supported. This paper discusses
      evidence of three common threats to SCV that arise from widespread
      recommendations or practices in data analysis, namely, the use of repeated
      testing and optional stopping without control of Type-I error rates, the
      recommendation to check the assumptions of statistical tests, and the use of
      regression whenever a bivariate relation or the equivalence between two variables
      is studied. For each of these threats, examples are presented and alternative
      practices that safeguard SCV are discussed. Educational and editorial changes
      that may improve the SCV of published research are also discussed.

PMID- 22952467
TI  - Glucose control and cardiovascular outcomes: reorienting approach.
AB  - Cardiovascular disease accounts for nearly 70% of morbidity and mortality in
      patients with diabetes mellitus. Strides made in diabetes care have indeed helped
      prevent or reduce the burden of microvascular complications in both type 1 and
      type 2 diabetes. However, the same cannot be said about macrovascular disease in
      diabetes. Several prospective trials so far have failed to provide conclusive
      evidence of the superiority of glycemic control in reducing macrovascular
      complications or death rates in people with advanced disease or those with long
      duration of diabetes. There are trends that suggest that benefits are restricted
      to those with lesser burden and shorter duration of disease. Furthermore, it is
      also suggested that benefits might accrue but it would take a longer time to
      manifest. Clinicians are faced with the challenge to decide how to triage
      patients for intensified care vs less intense care. This review focuses on
      evidence and attempts to provide a balanced view of the literature that has
      radically affected how physicians treat patients with macrovascular disease. It
      also takes cognizance of the fact that the natural course of the disease may be
      changing as well, possibly related to better overall awareness and possibly
      improved access to information about better individual healthcare. The review
      further takes note of some hard held notions about the pathobiology of the
      disease that must be interpreted with caution in light of new and emerging data.
      In light of recent developments ADA and EASD have taken step to provide some
      guidance to clinicians through a joint position statement. A lot more research
      would be required to figure out how best to manage macrovascular disease in
      diabetes mellitus. Glucocentric stance would need to be reconsidered, and
      attention paid to concurrent multifactorial interventions that seem to be
      effective in reducing vascular outcomes.

PMID- 22952466
TI  - BRET biosensors to study GPCR biology, pharmacology, and signal transduction.
AB  - Bioluminescence resonance energy transfer (BRET)-based biosensors have been
      extensively used over the last decade to study protein-protein interactions and
      intracellular signal transduction in living cells. In this review, we discuss the
      various BRET biosensors that have been developed to investigate biology,
      pharmacology, and signaling of G protein-coupled receptors (GPCRs). GPCRs form
      two distinct types of multiprotein signal transduction complexes based upon their
      inclusion of G proteins or beta-arrestins that can be differentially affected by
      drugs that exhibit functional selectivity toward G protein or beta-arrestin
      signaling. BRET has been especially adept at illuminating the dynamics of protein
      protein interactions between receptors, G proteins, beta-arrestins, and their
      many binding partners in living cells; as well as measuring the formation and
      accumulation of second messengers following receptor activation. Specifically, we
      discuss in detail the application of BRET to study dopamine and trace amine
      receptors signaling, presenting examples of an exchange protein activated by cAMP
      biosensor to measure cAMP, beta-arrestin biosensors to determine beta-arrestin
      recruitment to the receptor, and dopamine D2 receptor and trace amine-associated
      receptor 1 biosensors to investigate heterodimerization between them. As the
      biochemical spectrum of BRET biosensors expands, the number of signaling pathways
      that can be measured will concomitantly increase. This will be particularly
      useful for the evaluation of functional selectivity in which the real-time BRET
      capability to measure distinct signaling modalities will dramatically shorten the
      time to characterize new generation of biased drugs. These emerging approaches
      will further expand the growing application of BRET in the screening for novel
      pharmacologically active compounds.

PMID- 22952468
TI  - A phylogenetic analysis of the brassicales clade based on an alignment-free
      sequence comparison method.
AB  - Phylogenetic analyses reveal the evolutionary derivation of species. A
      phylogenetic tree can be inferred from multiple sequence alignments of proteins
      or genes. The alignment of whole genome sequences of higher eukaryotes is a
      computational intensive and ambitious task as is the computation of phylogenetic
      trees based on these alignments. To overcome these limitations, we here used an
      alignment-free method to compare genomes of the Brassicales clade. For each
      nucleotide sequence a Chaos Game Representation (CGR) can be computed, which
      represents each nucleotide of the sequence as a point in a square defined by the
      four nucleotides as vertices. Each CGR is therefore a unique fingerprint of the
      underlying sequence. If the CGRs are divided by grid lines each grid square
      denotes the occurrence of oligonucleotides of a specific length in the sequence
      (Frequency Chaos Game Representation, FCGR). Here, we used distance measures
      between FCGRs to infer phylogenetic trees of Brassicales species. Three types of
      data were analyzed because of their different characteristics: (A) Whole genome
      assemblies as far as available for species belonging to the Malvidae taxon. (B)
      EST data of species of the Brassicales clade. (C) Mitochondrial genomes of the
      Rosids branch, a supergroup of the Malvidae. The trees reconstructed based on the
      Euclidean distance method are in general agreement with single gene trees. The
      Fitch-Margoliash and Neighbor joining algorithms resulted in similar to identical
      trees. Here, for the first time we have applied the bootstrap re-sampling concept
      to trees based on FCGRs to determine the support of the branchings. FCGRs have
      the advantage that they are fast to calculate, and can be used as additional
      information to alignment based data and morphological characteristics to improve
      the phylogenetic classification of species in ambiguous cases.

PMID- 22952469
TI  - Optimized models for design of efficient miR30-based shRNAs.
AB  - Small hairpin RNAs (shRNAs) became an important research tool in cell biology.
      Reliable design of these molecules is essential for the needs of large functional
      genomics projects. To optimize the design of efficient shRNAs, we performed
      comparative, thermodynamic, and correlation analyses of ~18,000 miR30-based
      shRNAs with known functional efficiencies, derived from the Sensor Assay project
      (Fellmann et al., 2011). We identified features of the shRNA guide strand that
      significantly correlate with the silencing efficiency and performed multiple
      regression analysis, using 4/5 of the data for training purposes and 1/5 for
      cross validation. A model that included the position-dependent nucleotide
      preferences was predictive in the cross-validation data subset (R = 0.39).
      However, a model, which in addition to the nucleotide preferences included
      thermodynamic shRNA features such as a thermodynamic duplex stability and
      position-dependent thermodynamic profile (dinucleotide free energy) was
      performing better (R = 0.53). Software "miR_Scan" was developed based upon the
      optimized models. Calculated mRNA target secondary structure stability showed
      correlation with shRNA silencing efficiency but failed to improve the model.
      Correlation analysis demonstrates that our algorithm for identification of
      efficient miR30-based shRNA molecules performs better than approaches that were
      developed for design of chemically synthesized siRNAs (R(max) = 0.36).

PMID- 22952470
TI  - Genes contributing to genetic variation of muscling in sheep.
AB  - Selective breeding programs aiming to increase the productivity and profitability
      of the sheep meat industry use elite, progeny tested sires. The broad genetic
      traits of primary interest in the progeny of these sires include skeletal muscle
      yield, fat content, eating quality, and reproductive efficiency. Natural
      mutations in sheep that enhance muscling have been identified, while a number of
      genome scans have identified and confirmed quantitative trait loci (QTL) for
      skeletal muscle traits. The detailed phenotypic characteristics of sheep carrying
      these mutations or QTL affecting skeletal muscle show a number of common
      biological themes, particularly changes in developmental growth trajectories,
      alterations of whole animal morphology, and a shift toward fast twitch glycolytic
      fibers. The genetic, developmental, and biochemical mechanisms underpinning the
      actions of some of these genetic variants are described. This review critically
      assesses this research area, identifies gaps in knowledge, and highlights
      mechanistic linkages between genetic polymorphisms and skeletal muscle phenotypic
      changes. This knowledge may aid the discovery of new causal genetic variants and
      in some cases lead to the development of biochemical and immunological strategies
      aimed at enhancing skeletal muscle.

PMID- 22952471
TI  - Development of a scheme and tools to construct a standard moth brain for neural
      network simulations.
AB  - Understanding the neural mechanisms for sensing environmental information and
      controlling behavior in natural environments is a principal aim in neuroscience.
      One approach towards this goal is rebuilding neural systems by simulation.
      Despite their relatively simple brains compared with those of mammals, insects
      are capable of processing various sensory signals and generating adaptive
      behavior. Nevertheless, our global understanding at network system level is
      limited by experimental constraints. Simulations are very effective for
      investigating neural mechanisms when integrating both experimental data and
      hypotheses. However, it is still very difficult to construct a computational
      model at the whole brain level owing to the enormous number and complexity of the
      neurons. We focus on a unique behavior of the silkmoth to investigate neural
      mechanisms of sensory processing and behavioral control. Standard brains are used
      to consolidate experimental results and generate new insights through
      integration. In this study, we constructed a silkmoth standard brain and brain
      image, in which we registered segmented neuropil regions and neurons. Our
      original software tools for segmentation of neurons from confocal images,
      KNEWRiTE, and the registration module for segmented data, NeuroRegister, are
      shown to be very effective in neuronal registration for computational
      neuroscience studies.

PMID- 22952472
TI  - Methods to Assess the Protective Efficacy of Emollients against Climatic and
      Chemical Aggressors.
AB  - Exposure to harsh environmental conditions, such as cold and dry climate and
      chemicals can have an abrasive effect on skin. Skin care products containing
      ingredients that avert these noxious effects by reinforcement of the barrier
      function can be tested using in vivo models. The objective is to use in vivo
      models to assess the efficacy of emollients in protecting skin against climatic
      and chemical insults. A first model used a stream of cooled air to mimic cold
      wind. A second used sodium lauryl sulfate (SLS) under patch as chemical
      aggressor. In the model with simulated wind exposure, the untreated exposed area
      had a significant decrease in hydration. In contrast, application of an emollient
      caused a significant increase in hydration that was maintained after wind
      exposure. In the second model with SLS exposure, application of a barrier cream
      before SLS patch significantly reduced the dehydrating effect of SLS with a
      significant difference in variation between both areas. Application of the cream
      reduced TEWL, indicative of a physical reinforcement of the skin barrier. The two
      presented test methods, done under standardized conditions, can be used for
      evaluation of protective effect of emollient, by reinforcing the barrier function
      against experimentally induced skin dehydration.

PMID- 22952473
TI  - Recent developments in computed tomography for urolithiasis: diagnosis and
      characterization.
AB  - Objective. To critically evaluate the current literature in an effort to
      establish the current role of radiologic imaging, advances in computed tomography
      (CT) and standard film radiography in the diagnosis, and characterization of
      urinary tract calculi. Conclusion. CT has a valuable role when utilized prudently
      during surveillance of patients following endourological therapy. In this paper,
      we outline the basic principles relating to the effects of exposure to ionizing
      radiation as a result of CT scanning. We discuss the current developments in low
      dose CT technology, which have resulted in significant reductions in CT radiation
      doses (to approximately one-third of what they were a decade ago) while
      preserving image quality. Finally, we will discuss an important recent
      development now commercially available on the latest generation of CT scanners,
      namely, dual energy imaging, which is showing promise in urinary tract imaging as
      a means of characterizing the composition of urinary tract calculi.

PMID- 22952475
TI  - Hypertrophic cardiomyopathy mimicking acute anterior myocardial infarction
      associated with sudden cardiac death.
AB  - Hypertrophic cardiomyopathy is the most common genetic disease of the heart. We
      report a rare case of hypertrophic obstructive cardiomyopathy mimicking an acute
      anterior myocardial infarction associated with sudden cardiac death. The patient
      presented with acute ST elevation myocardial infarction and significant elevation
      of cardiac enzymes. Cardiac catheterization showed some atherosclerotic coronary
      artery disease, without significant stenosis. Echocardiography showed left
      ventricular hypertrophy with a left ventricular outflow tract obstruction; the
      pressure gradient at rest was 20 mmHg and became severe with the Valsalva
      maneuver (100 mmHg). There was no family history of sudden cardiac death. Six
      days later, the patient suffered a syncope on his way to magnetic resonance
      imaging. He was successfully resuscitated by ventricular fibrillation.

PMID- 22952476
TI  - Vitiligo in a Patient Treated with Interferon Alpha-2a for Behcet's Disease.
AB  - Behcet's disease (BD) and vitiligo are diseases of unknown etiology. Interferon
      (IFN) alpha therapy is commonly used in Behcet uveitis. Interferon treatment in
      various diseases have also been observed causing certain autoimmune diseases such
      as vitiligo because of its immunomodulatory activity. The association between IFN
      therapy and vitiligo has been reported in the literature. We report a 21-year-old
      man with BD in whom vitiligo occurred during IFN treatment. To the best of our
      knowledge, this is the first reported case of such an association.

PMID- 22952474
TI  - Roles for endothelial cells in dengue virus infection.
AB  - Dengue viruses cause two severe diseases that alter vascular fluid barrier
      functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The
      endothelium is the primary fluid barrier of the vasculature and ultimately the
      effects of dengue virus infection that cause capillary leakage impact endothelial
      cell (EC) barrier functions. The ability of dengue virus to infect the
      endothelium provides a direct means for dengue to alter capillary permeability,
      permit virus replication, and induce responses that recruit immune cells to the
      endothelium. Recent studies focused on dengue virus infection of primary ECs have
      demonstrated that ECs are efficiently infected, rapidly produce viral progeny,
      and elicit immune enhancing cytokine responses that may contribute to
      pathogenesis. Furthermore, infected ECs have also been implicated in enhancing
      viremia and immunopathogenesis within murine dengue disease models. Thus dengue
      infected ECs have the potential to directly contribute to immune enhancement,
      capillary permeability, viremia, and immune targeting of the endothelium. These
      effects implicate responses of the infected endothelium in dengue pathogenesis
      and rationalize therapeutic targeting of the endothelium and EC responses as a
      means of reducing the severity of dengue virus disease.

PMID- 22952477
TI  - Tuboovarian Abscess due to Colonic Diverticulitis in a Virgin Patient with Morbid
      Obesity: A Case Report.
AB  - Since tuboovarian abscess is almost always a complication of pelvic inflammatory
      disease, it is rarely observed in virgins. A 30-year-old virgin patient presented
      with pelvic pain, fever, and vaginal spotting for the previous three weeks. Her
      abdominopelvic computed tomography scan revealed bilateral multiseptated cystic
      masses with prominent air-fluid levels suggesting tuboovarian abscesses. The
      sigmoid colon was lying between two tuboovarian masses, and its borders could not
      be distinguished from the ovaries. The patient was presumed to have bilateral
      tuboovarian abscesses which developed as a complication of the sigmoid
      diverticulitis. She was administered intravenous antibiotic therapy followed by
      percutaneous drainage under ultrasonographic guidance. She was discharged on the
      twenty second day with prominent clinical and radiological improvement.
      Diverticulitis may be a reason for development of tuboovarian abscess in a virgin
      patient. Early recognition of the condition with percutaneous drainage in
      addition to antibiotic therapy helps to have an uncomplicated recovery.

PMID- 22952478
TI  - Mycoplasma pneumoniae-Induced-Stevens Johnson Syndrome: Rare Occurrence in an
      Adult Patient.
AB  - Stevens-Johnson syndrome (SJS) is an uncommon occurrence in Mycoplasma pneumoniae
      (M. pneumoniae) infection (1-5%) and has been mainly reported in children and
      young adults. We present a case of SJS in a 32-year-old male induced by M.
      pneumoniae infection. This patient presented with fever, cough, and massive
      occupation of mucus membranes with swelling, erythema, and necrosis accompanied
      by a generalized cutaneous rash. He clinically responded after treatment with
      antibiotics and IVIG. SJS is usually a drug-induced condition; however, M.
      pneumoniae is the commonest infectious cause and should be considered in the
      differential diagnosis.

PMID- 22952479
TI  - Giant Dilatation of the Right Coronary Aortic Bulb with Compression of the Right
      Ventricular Outflow Tract Mimicking a Ventricular Septal Defect: Diagnostic
      workup Using Echocardiography, Heart Catheterization, and Cardiac Computed
      Tomography.
AB  - Annuloaortic ectasia is a relatively rare diagnosis. Herein, we report an unusual
      case of an annuloaortic ectasia with asymmetric dilatation of the right coronary
      bulb mimicking a membranous ventricular septal defect (VSD) with Eisenmenger
      reaction by transthoracic echocardiography. Aortic angiography showed a dilated
      aortic root and moderate aortic regurgitation. Right cardiac catheterization, on
      the other hand, exhibited normal pulmonary artery blood pressure and normal
      pulmonary resistance, whereas normal venous gas values were measured throughout
      the caval vein and the right atrium, excluding relevant left-right shunting.
      Further diagnostic workup by cardiac computed tomography angiography (CCTA)
      unambiguously illustrated the asymmetric geometry of the ectatic aortic cusp and
      root causing compression of the right heart and of the right ventricular (RV)
      outflow tract. After review of echocardiographic acquisitions, the blood flow
      detected between the left and right ventricles (mimicking VSD) was interpreted as
      turbulent inflow from the left ventricle into the ectatic right coronary cusp.
      Furthermore, elevated pulmonary artery blood pressure measured by
      echocardiography was attributed to "functional pulmonary stenosis" due to
      compression of the RV outflow tract by the aorta, as demonstrated by CCTA.

PMID- 22952480
TI  - Mullerian adenosarcoma of uterus with sarcomatous overgrowth and heterologous
      component associated with stromal deposit in omentum: a case report and review of
      the literature.
AB  - Background. Mullerian adenosarcoma with sarcomatous overgrowth (MASO) is a very
      rare variant of uterine sarcomas first described by Clement et al. as early as
      1974. The presence of heterologous sarcomatous components is associated with
      aggressive biological behavior. Case Presentation. This is a case report of a 62
      year female (P(2 + 0)) presenting with postmenopausal vaginal bleeding. Her
      preoperative USG revealed subserosal fibroid with adherent omentum. She underwent
      abdominal hysterectomy with bilateral oophorectomy. Histopathological diagnosis
      of resected specimen was Mullerian adenosarcoma with sarcomatous overgrowth and
      presence of heterologous elements involving body of the uterus. The whole
      thickness of the myometrium was involved along with the presence of serosal
      nodules and omental deposits of sarcomatous component. Conclusion. MA is
      considered as a low-grade malignant tumor, but MASO is a high-grade tumor
      frequently associated with invasion and metastasis with poor treatment outcome.
      Because of its rarity, correct identification of these tumors and distinction
      from other uterine sarcomas are a challenging job and hence its morphological
      features merits attention.

PMID- 22952481
TI  - Efficacy and Safety of Oral Combination of Yohimbine and L-arginine (SX) for the
      Treatment of Erectile Dysfunction: a multicenter, randomized, double blind,
      placebo-controlled clinical trial.
AB  - OBJECTIVE: The objective of this study was to assess the efficacy and safety of
      SX (combination of yohimbine and L-arginine) in the treatment of erectile
      dysfunction (ED). METHODS: This trial was a 4-week, double blind study of
      parallel groups of patients with mild to moderate ED. Forty married male patients
      with ED of mild-to-moderate severity were screened for the study entry;among
      them, those aged 25-50 who reported a minimum of a- 3-month history of ED were
      eligible to enroll in this study. The severity of ED was based on EF domain
      scores on the international index of erectile function (IIEF). The scores of 15
      25 was considered as mild to moderate ED. Patients were randomized to receive one
      capsule of SX or placebo on demand in a 1:1 ratio using a computer-generated
      code. RESULTS: The difference between the two groups was significant at week 4
      (endpoint) (P=0.03). Four adverse events were observed over the study. The
      difference between the SX and placebo was not significant in the frequency of
      adverse events. CONCLUSION: This study indicates that SX is safe and effective
      for the treatment of mild to moderate ED at least in the short-term.

PMID- 22952482
TI  - Effects of Herbal vigRX on Premature Ejaculation: A randomized, double-blind
      study.
AB  - OBJECTIVE: We conducted a double-blind, placebo-controlled study to determine the
      efficacy of an herbal sexual supplement (vigRX) on premature ejaculation (PE).
      METHOD: A randomized double blind study was conducted on a fixed dose of herbal
      vigRX at Roozbeh Psychiatry Hospital, Tehran University of Medical Sciences. The
      sample consisted of 85 married patients diagnosed with primary PE according to
      Diagnostic and Statistical Manual of Mental Disorders. Each patient underwent
      diagnostic evaluation by one trained psychiatrist, using Structured Clinical
      Interview for DSM-IV-TR. Each patient was evaluated by researchers to exclude the
      organic sexual dysfunctions. The patients were randomly assigned in to two
      groups: group 1 consisting of 42 patients receiving placebo, and group 2
      consisting of 43 patients receiving 540 mg herbal vigRX for a 4-week treatment
      course. The effects of the drug on the ejaculatory function in each group were
      assessed by the intravaginal ejaculation latency time (IELT), and the Chinese
      Index of Premature Ejaculation (CIPE) before and at the end of the treatment
      course. Statistical analysis was performed using SPSS software (15th version).
      RESULTS: The mean IELT increased 22.4 and 32.0 seconds in the placebo and the
      vigRX group respectively after the treatment course. The mean IELT differences
      between the two groups was not significant. The mean CIPE score increased 2.40
      and 4.37 in the placebo and the vigRX group respectively. The mean CIPE score
      differences between the two groups was not significant.No side effect was
      reported by the subjects in neither groups during the treatment course.
      CONCLUSION: Although the improvement in IELT and CIPE scores in the herbal vigRX
      group was more than the placebo group, this difference was not statistically
      significant. The increasing of IELT and CIPE score in the placebo group may be
      due to the placebo effects. Further studies with higher vigRX doses, greater
      sample size and longer treatment courses are warranted.

PMID- 22952483
TI  - Training health professionals to conduct family education for families of
      patients with first-episode psychosis: adherence to protocol.
AB  - OBJECTIVE: The implementation of family psychoeducation at the service delivery
      level is not without difficulty. Few mental health professionals receive special
      training to work with families especially in Iran. The aim of the present study
      was to evaluate the effectiveness of training health professionals in terms of
      their adherence to protocol. METHOD: Eight professionals (general practitioners,
      nurses and social workers) participated in a training program for health
      professionals as part of the Roozbeh First-Episode Psychosis Program (RooF) to
      conduct family psychoeducation. Training included a 3-day- workshop and 12
      supervision sessions during the course of the implementation of the
      psychoeducation program. The family psychoeducation sessions (multiple-family
      group or single-family home-based) were tape-recorded. Transcripts of the
      audiotaped sessions were analyzed based on the content of the manual and were
      scored accordingly. RESULTS: Twenty-four recorded sessions were analyzed in terms
      of the adherence to protocol, the number of questions and the time for each
      session. The overall rating showed a 72% adherence to the protocol. Multiple
      family group sessions had a higher rate compared to the single-family home-based
      family psychoeducation sessions (79% to 69%) as well as the time spent and
      questions asked. The rate of adherence to the protocol of conducting the family
      psychoeducation sessions had not changed over time. CONCLUSION: Considering the
      amount of time taken for training and supervision, the level of adherence to the
      protocol was satisfactory. Tape recording sessions and regular supervision would
      be beneficial following specialized training. Further research is needed to
      tailor the amount of training and supervision required for professionals to
      conduct family psychoeducation programs in different settings.

PMID- 22952484
TI  - The effects of histaminergic agents in the nucleus accumbens of rats in the
      elevated plus-maze test of anxiety.
AB  - OBJECTIVE: The nucleus accumbens (NAc) receive histaminergic neurons from
      tuberomammillary nuclei. There are reports indicating that central histamine
      systems are involved in many physiological behavioral processes, including
      anxiety. The aim of the present study was to assess whether the histaminergic
      system of the NAc is involved in anxiety-related behaviors. METHODS: Rats were
      anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus
      xylazine and then were placed in a stereotaxic apparatus. In addition, two
      stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell.
      Seven days after recovery from surgery, the behavioral testing was started. As a
      model of anxiety, the elevated plus maze which is a useful test to investigate
      the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar
      rats. RESULTS: Intra-NAc administration of histamine (0.01, 0.1 and 1 ug/rat)
      increased the percentage of open arm time (%OAT) and open arm entries (%OAE), but
      not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral
      microinjections of different doses of the H(1) receptor antagonist pyrilamine
      (0.001, 0.01, 0.1 and 1 ug/rat) or the H(2) receptor antagonist ranitidine
      (0.001, 0.01, 0.1 and 1 ug/rat) into the NAc increased %OAT and %OAE, but not
      locomotor activity. However, both histamine and histamine receptor antagonists
      showed an anxiolytic-like effect; the antagonists (1 ug/rat) also decreased the
      histamine response. CONCLUSION: The results may indicate a modulatory effect for
      the H(1) and H(2) histamine receptors of nucleus accumbens in the anxiety
      behavior of rats.

PMID- 22952485
TI  - Effect of Early Intervention with Omega-3 on Insulin Resistance in Patients
      Initiated on Olanzapine with either Sodium Valproate or Lithium: A randomized,
      Double-blind, Placebo-Controlled Trial.
AB  - OBJECTIVE: Metabolic side effects of the second generation (atypical)
      antipsychotics have been a forefront of attention since their availability. One
      common concern is the development of hyperglycemia and insulin resistance. The
      aim of this study was to evaluate the effect of early initiation of omega-3 fatty
      acids supplementation on glucose-insulin homeostasis in a group of psychiatric
      patients under treatment with olanzapine and sodium valproate or lithium
      combination. METHOD: In a double-blind design, eligible participants with
      schizophrenia, bipolar I, and schizoaffective disorders who were initiated on
      olanzapine combination with sodium valproate or lithium were randomly assigned to
      receive omega-3 or identical placebo capsules for 6 weeks. Fasting blood sugar
      (FBS), insulin and HbA(1c) were measured at the baseline and at the end of the
      6(th) week. Homeostatic model assessment of insulin resistance (HOMA-IR), as a
      measure of insulin resistance, was also determined at the same times. RESULTS: At
      the end of the study, no significant difference was observed between the two arms
      in terms of FBS, fasting insulin, HbA(1c) and HOMA-IR. However, trends toward
      decreasing both fasting insulin levels (p=0.06) and HOMA-IR (p=0.07) were noted
      in the group receiving omega-3. No significant changes in the outcome variables
      were observed from the baseline to the final measurements in both groups.
      CONCLUSION: This study noted that adding omega-3 fatty acids at the commencement
      of olanzapine combination therapy with valproate or lithium could not favorably
      influence glucose-insulin homeostasis. However, trends toward a decrease in
      insulin levels (p=0.06) and HOMA-IR (p=0.07) observed in patients receiving omega
      3 suggest a possible beneficial role of this supplement in this population and,
      therefore, warrant further evaluation.

PMID- 22952486
TI  - Association of premorbid adjustment with symptom profile and quality of life in
      first episode psychosis in a tertiary hospital in tehran, iran.
AB  - OBJECTIVE: Poor premorbid adjustment has been reported to be a predictor of more
      severe psychotic symptoms and poor quality of life in such psychotic disorders as
      schizophrenia. However, most studies were performed on chronic schizophrenic
      patients, and proposed the likelihood of recall biases and the effect of
      chronicity. The aim of this study was to investigate these factors in a sample of
      first episode psychotic patients, as a part of Roozbeh first episode psychosis
      project (RooF). METHOD: Premorbid adjustment was assessed using Premorbid
      Adjustment Scale (PAS) in 48 patients with the first psychotic episode who were
      admitted to Roozbeh Psychiatric Hospital. The severity of symptoms was measured
      using Positive and Negative Scale (PANSS) in three subgroups of positive,
      negative and general subscales. Quality of life was measured using WHO QOL , and
      Global Assessment of Functioning (GAF) was also measured. RESULTS: The mean age
      was 24 years. Poor Premorbid adjustment in late adolescence was significantly
      associated with more severe symptoms according to PANSS negative symptoms
      (p=0.019, r=0.44). Furthermore, sociability and peer relationship domains had a
      positive correlation with PANSS negative subscale scores (r=0.531, p=0.002 and
      r=0.385, p=0.03, respectively). There were no significant differences between
      males and females in premorbid adjustment. Furthermore, this study failed to show
      any differences between affective and non-affective psychosis in premorbid
      functioning. CONCLUSION: Our study confirms poor premorbid adjustment association
      with more severe negative symptoms and poor quality of life in a sample of
      Iranian first episode psychotic patients.

PMID- 22952487
TI  - Personal Well-being and Stress Symptoms in Wives of Iranian Martyrs, Prisoners of
      wars and Disabled Veterans.
AB  - OBJECTIVE: This study was conducted to compare the personal well-being among the
      wives of Iranian veterans living in the city of Qom. METHOD: A sample of 300 was
      randomly selected from a database containing the addresses of veteran's families
      at Iran's Veterans Foundation in Qom (Bonyad-e-Shahid va Omoore Isargaran). The
      veterans' wives were divided into three groups: wives of martyrs (killed
      veterans), wives of prisoners of war, and wives of disabled veterans. The Persian
      translation of Personal Well-being Index and Stress Symptoms Checklist (SSC) were
      administered for data collection. Four women chose not to respond to Personal
      Well-being Index. Data were then analyzed using linear multivariate regression
      (stepwise method), analysis of variance, and by computing the correlation between
      variables. RESULTS: Results showed a negative correlation between well-being and
      stress symptoms. However, each group demonstrated different levels of stress
      symptoms. Furthermore, multivariate linear regression in the 3 groups showed that
      overall satisfaction of life and personal well-being (total score and its
      domains) could be predicted by different symptoms. CONCLUSION: Each group
      experienced different challenges and thus different stress symptoms. Therefore,
      although they all need help, each group needs to be helped in a different way.

PMID- 22952488
TI  - The Comparison of Relationship Beliefs and Couples Burnout in women who apply for
      Divorce and Women Who Want to Continue their Marital Life.
AB  - OBJECTIVE: The aim of this study was to examine the comparison of relationship
      beliefs and couples burnout in women who apply for divorce and women who want to
      continue their marital life. METHOD: for this study, 50 women who referred to
      judicial centers and 50 women who claimed they wanted to continue their marital
      life were randomly selected. Participants were asked to complete the relationship
      beliefs inventory and marital burnout questionnaires. In this study, descriptive
      statistical methods such as standard deviation, mean, t- students for independent
      groups, correlation, multi-variable regression and independent group's
      correlation difference test were used. RESULTS: The comparison between the
      relationship beliefs of the 2 groups (those wanting to divorce and women wanting
      to continue their marital life) was significantly different (p<0/1). In addition,
      the comparison of marital burnout was significantly different in the 2 groups
      (p<0/1). DISCUSSION: Women who were about to divorce were significantly different
      from those who wanted to continue their marital relationship in the general
      measure of the relationship beliefs and factors of "believing that disagreement
      is destructive and their partners can not change their undesirable behaviors". In
      other words, women who were applying for divorce had more unreasonable thoughts
      and burnout compared to those who wanted to continue their marital life.

PMID- 22952490
TI  - Femicomfort in the treatment of premenstrual syndromes: a double-blind,
      randomized and placebo controlled trial.
AB  - OBJECTIVE: Premenstrual syndromes (PMS) affecting 20-40% of women of reproductive
      age. The aim of this double blind and placebo controlled trial was to investigate
      whether femicofort a supplement contains Vitamin B6, Vitamin E and evening
      primrose oil could relieve symptoms of PMS. METHOD: This was a randomized and
      double blind clinical trial. The trial was conducted between November 2009 and
      April March 2010. Women aged 20 to 45 years with regular menstrual cycles and
      experience of PMS symptoms (According to the current diagnostic criteria proposed
      by the American College of Obstetrics and Gynecology) for at least 6 months were
      eligible for the study. Patients were randomized to receive femicomfort or
      placebo in a 1: 1 ratio using a computer-generated code. The assignments were
      kept in sealed, opaque envelopes until the point of analysis of data. In this
      double-blind, patients were randomly assigned to receive capsule of femicomfort
      (Group A) or capsule placebo for two menstrual cycles (cycles 3 and 4). The
      primary outcome measure was the Daily Symptom Report, a checklist of 17
      premenstrual symptoms rated from 0 to 4 according to their severity throughout
      the menstrual cycle. Secondary outcome measure was Hamilton Depression Rating
      Scale (17-item). RESULTS: Femicomfort at this dose was found to be effective in
      relieving symptoms of PMS. The difference between the femicomfort and placebo in
      the frequency of side effects was not significant. CONCLUSION: The results of
      this study indicate the efficacy of femicomfort in the treatment of PMS.

PMID- 22952489
TI  - Postpartum depression and role of serum trace elements.
AB  - Postpartum depression (PPD) is a major depressive disorder that most often
      emerges within 6 to 12 weeks of delivery, but can happen any time up to 1 year
      after birth. In developed countries, the incidence of postnatal depression is
      about 10-15% in adult women depending upon the diagnostic criteria, timing of
      screening and screening instruments used. Mothers with depressive symptoms have
      been found to have more complex behavioral contacts with their children; this
      situation can damage family relationships, and even leads to infanticide. Various
      pathophysiologies are proposed for postpartum depression: Nutritional
      deficiencies, iron deficiency anemia, rapid decrease in the levels of
      reproductive hormones following delivery, alterations in hypothalamic-pituitary
      adernocortical mechanism and alterations in neurotransmitter levels. Among
      pathophysiologies of postpartum depression, the role of trace elements is
      highlighted. The purpose of this review is to assess the role of trace elements
      including zinc, magnesium, iron and copper in PPD. Zinc as a trace element has
      the second highest concentration of all transition metals in the brain, and its
      deficiency is associated with behavioral disturbances. Lower zinc blood
      concentration was found in women with postpartum depression. Another trace
      element, magnesium, also influences the nervous system via its actions on the
      release and metabolism of neurotransmitters. Various studies have focused on
      antidepressant-like effects of magnesium and its deficiency has been reported in
      depression. Depletion of magnesium stores during pregnancy is hypothesized to be
      the cause of postpartum depression. Iron deficiency is the most common single
      nutrient deficiency in the world. There is an association between anemia and
      depressive disorders. Copper has been recognized as an essential element for many
      years. Iron also plays a vital role in neurological disorders and its levels are
      relevant to postpartum depression. Involvement of trace elements can be seen in
      pathophysiologies of PPD in different ways. Therefore, trace element
      supplementation can be an alternative treatment for patients with PPD.

PMID- 22952491
TI  - Psychological Dimensions in Patients admitted in Imam Khomeini General Hospital
      in Tehran.
AB  - OBJECTIVE: The aim of this study was to assess the mental health of patients
      admitted in Internal medicine, Surgery and Gynecology wards of Imam Khomeini
      Hospital of Tehran in 2009. METHOD: The symptom checklist-90-R (SCL-90-R)
      questionnaire was administered for 93 patients in internal, surgical and
      gynecological wards of Imam Khomeini hospital in 2009. RESULTS: In this study,
      the mean age was (32.89+/-12.69) with a range of 14 to 70 years old. 42 patients
      (44.7%) were male and 52 (59.6%) were female; 56 patients (59.6%) were married
      and 37 (40.4%) were single. There is a significant relationship between gender&
      marital status (P<0.04). According to cut of point of Global Severity Index (GSI)
      which was reported in a study (0.7), 58.1 percent of the patients have different
      levels of psychiatric problems (GSI>0.7). In psychiatric symptoms, somatization
      has the highest prevalence (90.5%), and depression (77.9%) and anxiety (71.6%)
      have a higher prevalence than other symptoms among patients who suffer from
      psychiatric problems. CONCLUSION: According to the result of the current study,
      there is a high prevalence of psychiatric problems among the admitted patients in
      Internal medicine, Surgery and Gynecology wards of a general hospital according
      to SCL-90-R questionnaire. This study advises that more attention be given to
      mental health in general hospitals.

PMID- 22952492
TI  - Frequency of Psychological Disorders amongst Children in Urban Areas of Tehran.
AB  - OBJECTIVE: To evaluate the frequency of different psychiatric disorders among 7
      to 12 years old children in urban areas of Tehran. METHOD: A sample of 799
      children (6 to 11 years old) were selected from 250 clusters of the entire 22
      municipality areas of Tehran using a multistage sampling method from 250 clusters
      from the entire 22 municipality areas of Tehran.. After responding to a Persian
      version of the Strengths and Difficulties Questionnaire (SDQ) parent-report form,
      the Persian version of Kiddie Schedule for Affective Disorders and Schizophrenia 
      Present and Lifetime (K-SADS-PL) was administered to 241 children and their
      families. The frequency of child psychological disorders was determined using the
      results of K-SADS-PL. RESULTS: The overall frequency of any psychological
      disorders in the sample of children was 17.9 percent. Among the interviewed
      children childrenwho were interviewed, the most prevalent diagnoses were
      Attention-Deficit/Hyperactivity Disorder (ADHD) (8.6 percent)8.6%, Oppositional
      Defiant Disorder (ODD) (7.3 percent)7.3%, and separation anxiety disorder (SAD)
      (5.9 percent)5.9%. There were not any statistically significant differences
      between sexes in the frequency of psychological disorders except enuresis that
      was more frequent in the boys and anorexia nervosa that was observed more
      frequently in the girls. CONCLUSION: Higher frequency of ADHD and ODD and SAD
      among the studied children warrantswarrants more specific evaluation of frequency
      and possible causes of these high frequency rates. The frequency of psychological
      disorders in the studied children was comparable to the that of other studies.

PMID- 22952493
TI  - The effectiveness of emotion regulation training and cognitive therapy on the
      emotional and addictional problems of substance abusers.
AB  - OBJECTIVES: The purpose of this study was to investigate the effectiveness of
      emotional regulation training group therapy, based on Dialectical Behavioral
      Therapy (DBT) and Cognitive Therapy, on improving emotional regulation and
      distress tolerance skills and relapse prevention in addicts. METHOD: In a
      quasiexperimental study, 39 patients with the diagnosis of opioid dependence
      based on DSM-IV criteria were randomly assigned in to two experimental and one
      control groups. The experimental groups took 10 ninety-minute sessions of group
      therapy. The subjects were evaluated using the Opiate Treatment Index (OPI),
      General Health Questionnaire-28 (GHQ-28), and Distress Tolerance and Difficulties
      in Emotion Regulation Scales prior to the start of treatment, and at the
      sixteenth session. The control group did not take group therapy and was merely
      treated with naltrexone. Data were analyzed using repeated measures ANOVA and
      chi2 test. RESULTS: Scheffe test showed that both emotion regulation training and
      cognitive therapy were more effective than naltrexone increasing distress
      tolerance, emotion regulation enhancement, and decreasing the amount of drug
      abuse, health improvement, social functioning, somatic symptoms, anxiety, social
      dysfunction and depression enhancement (P<0.05). In addition, emotion regulation
      training was more effective than cognitive therapy, increasing distress tolerance
      and emotional regulation enhancement (p<0.05). CONCLUSION: It seems that DBT
      skill training increase the effectiveness of pharmacotherapy and is more
      effective than cognitive therapy.

PMID- 22952494
TI  - Stress and Personal Well-being among a Sample of Iranian Disabled Veteran's
      Wives.
AB  - OBJECTIVE: The aim of this study was to compare overall life satisfaction,
      subjective well-being, family stress, and stress symptoms of wives of three
      groups of Iranian disabled veterans. METHOD: Participants included 97 wives of
      three groups of disabled veterans (Group 1with 25-49% disability; Group 2 with 50
      69% disability; and Group 3 with larger or equal to 70% disability). The
      participants were selected randomly by computers of Iranian Martyrs and Veterans
      Foundations. Personal Well-being Index-Adult, Family Inventory of Life Events and
      Changes and Stress-related Symptoms Inventory were used to measure overall life
      satisfaction, family resources of stress and stress symptoms. Data were analyzed
      by ANOVA and linear multivariate regression analysis. RESULTS: Results showed
      that there are no differences in stress symptoms among the 3 groups. However, the
      wives of group 2 showed less stress and more global life satisfaction and
      subjective well-being; whereas, wives of group 3 showed more family stress and
      less global life satisfaction and subjective well-being. However, the wives of
      group 1 showed less global life satisfaction, subjective well-being and less
      family stress. CONCLUSION: Based on other studies, the results of group 1 is
      abnormal. This abnormality in results is due to two reasons: first, the
      participants tried to show poorer quality of life. Second, these women have not
      received enough facilities and services. Therefore, they lost their natural
      homeostasis. It seems that the last reason is more real because of equality in
      stress symptoms between the 3 groups.

PMID- 22952495
TI  - The effects of chronic partial sleep deprivation on cognitive functions of
      medical residents.
AB  - OBJECTIVES: Because of on-call responsibilities, many medical residents are
      subjected to chronic partial sleep deprivation, a form of sleep restriction
      whereby individuals have chronic patterns of insufficient sleep. It is unclear
      whether deterioration in cognitive processing skills due to chronic partial sleep
      deprivation among medical residents would influence educational exposure or
      patient safety. METHOD: Twenty-six medical residents were recruited to
      participate in the study. Participants wore an Actigraph over a period of 5
      consecutive days and nights so their sleep pattern could be recorded. Thirteen
      participants worked on services that forced chronic partial sleep deprivation (<6
      hours of sleep per 24h for 5 consecutive days and nights). The other thirteen
      residents worked on services that permitted regular and adequate sleep patterns.
      Following the 5-day sleep monitoring period, the participants completed the three
      following cognitive tasks: (a) the Wisconsin Card Sorting Test (WCST) to assess
      abstract reasoning and prefrontal cortex performance; (b) the Time Perception
      Task (TPT) to assess time estimation and time reproduction skills; and (c) the
      Iowa Gambling Task (IGT) to assess decision-making ability. RESULTS: The results
      of independent samples t-tests found no significant differences between the group
      who was chronically sleep deprived and the group who rested adequately (all ps >
      .05). CONCLUSION: THESE RESULTS MAY HAVE EMERGED FOR SEVERAL POSSIBLE REASONS:
      (a) chronic partial sleep deprivation may have a lesser impact on prefrontal
      cortex function than on other cognitive functions; (b) fairly modest chronic
      sleep restriction may be less harmful than acute and more significant sleep
      restriction; or (c) our research may have suffered from poor statistical power.
      Future research is recommended.

PMID- 22952496
TI  - Afebrile Neuroleptic Malignant Syndrome associated with Fluphenazine decanoate: A
      case report.
AB  - Neuroleptic Malignant Syndrome (NMS) is unusual but could be a lethal reaction
      associated with neuroleptic drugs. It occurs in almost 0.07-2.2% of patients
      under treatment with neuroleptics. There are some medical treatments that may
      also be helpful for its treatment, including dopamine agonists, muscle relaxants,
      and electroconvulsive therapy (ECT). We present this case to alert the clinicians
      to the potential for inducing afebrile NMS.Our case is a 41-year-old man with a
      history of schizophrenia showing signs and symptoms in accordance with NMS, 2
      weeks after receiving one dose of 12.5 mg fluphenazine decanoate, abruptly
      following the 3rdsession of ECT. The patient presented with decreased level of
      consciousness, muscular rigidity, waxy flexibility, mutism, generalized tremor,
      sever diaphoresis and tachycardia which progressed during the previous 24 h.
      Laboratory data indicated primarily leukocytosis, an increasing level of
      creatinine phosphokinase and hypokalemia during the next 72h.In patients
      receiving antipsychotics, any feature of NMS should carefully be evaluated
      whether it is usual or unusual particularly in patients receiving long acting
      neuroleptics.

PMID- 22952497
TI  - Religious cognitive-emotional therapy: a new form of psychotherapy.
AB  - From the ancient times up to this date, it has been thought that religion and
      spirituality have important effects on human being's mental life. However, some
      psychologists and psychotherapists have ignored this role, and thus neglected to
      study the effects of applying religion and spirituality in psychotherapy.
      However, many psychologists and psychotherapists have recently studied the
      relationship between religion or spirituality and mental health; or used
      religious interventions in psychotherapies. Although different kinds of religious
      psychotherapies have been proposed, no comprehensive theory has been presented in
      this area. In this article a scientific, comprehensive and applied spiritual
      method of psychotherapy is suggested. Religious Cognitive- Emotional Therapy
      (RCET) is a new form of cognitive therapy that uses the basic religious beliefs
      and insights in psychotherapy. RCET is a new integration of cognitive,
      humanistic, and existential psychotherapies that takes into account religious
      beliefs and insights of the clients. RCET is an effective method of psychotherapy
      for the treatment of those who suffer from identity crisis, depression, and
      anxiety; and it can be developed to address other psychological disorders as
      well. Because RCET is a new approach, practically is needed to do further
      theoretical research in this area.

PMID- 22952498
TI  - The prevalence of Attention Deficit Hyperactivity Disorder in Iran: A systematic
      review.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder of childhood. Children with ADHD may experience
      significant functional problems. Our objective was to examine the prevalence of
      ADHD and its subtypes in Iran. METHODS: Pubmed, ISI web of science, psychinfo,
      Iranpsych, Iranmedex, Irandoc were searched. Irandoc, Iranmedex and Iranpsych are
      Iranian databases of which the last one is especially for psychiatry and
      psychology literature. INCLUSION CRITERIA WERE: conducting studies by random
      sampling, using valid instruments to assess ADHD diagnosis or symptoms,and
      presenting a prevalence of ADHD or attention deficit and / or hyperactivity
      symptoms. RESULTS: After quality assessment, 16 studies were accepted. Their
      estimation of prevalence was different as different scales were used. Hyperactive
      type was more prevalent in boys, and inattentive type was more prevalent in
      girls. CONCLUSION: Being aware of the epidemiology of ADHD in Iran helps us to
      make improvements in planning the allocation of funds for mental health services.
      Using one instrument in studying the prevalence of ADHD in a population may lead
      to more precise estimations.

PMID- 22952499
TI  - Children and Their Parent's Perceptions of Symptom Severity and Treatment
      Preference for Tourette Syndrome.
AB  - OBJECTIVES: This study surveys children and their parent's perceptions, and their
      treatment preference of significant/bothersome symptoms in children with Tourette
      syndrome. METHODS: Thirty five children and adolescents who referred to an out
      patient clinic of a Child Psychiatry Clinic were selected as subjects for this
      study. The children and their parents were interviewed about their perception of
      significant/bothersome symptoms of motor tics, vocal tics, learning difficulties,
      attention deficit disorder, hyperactivity, obsessions, compulsions, and rage
      attacks. RESULTS: About two thirds of the subjects had symptom of rage.
      Inattentiveness and hyperactivity were observed in more than half of the
      children. There was a statistically significant difference between parents and
      their children in frequency of motor tics and rage attacks. Children reported the
      necessity for controlling and management of these symptoms less than their
      parents. DISCUSSION: The rates of motor, vocal tics and rage attacks in the
      Iranian sample are similar to other studies. Rage attack is one of the most
      common significant/bothersome symptoms reported that should be treated. While
      motor tics were not rated among the most common features that should be treated
      in a study in Canada, it was the most common significant/bothersome symptom in
      Iran. Parents perceive motor tics and rage attacks as more significant/bothersome
      symptoms compared to children.

PMID- 22952500
TI  - The factors associated with suicide ideation in Iranian soldiers.
AB  - OBJECTIVE: The study focuses on psychosocial variables related to suicide
      ideation in young soldiers. METHOD: 1329 Soldiers were randomly selected from the
      Infantry Forces in different regions. All the soldiers were requested to complete
      the Beck Scale for Suicide Ideation (BSSI) as well as General Health
      Questionnaire (GHQ-28). Data were analyzed using correlation tests. RESULTS: The
      results revealed that psychological factors, negative family background,
      environmental and task-related problems, and sociodemographic problems were
      significantly associated with suicide ideation. DISCUSSION: Overall, suicide
      ideation could be prevented if soldiers with psychosocial problems were
      identified and the Army officials applied appropriate methods to solve these
      psychological problems.

PMID- 22952501
TI  - The role of social support and coping strategies on mental health of a group of
      Iranian disabled war veterans.
AB  - OBJECTIVE: The purpose of this study was to examine the role of social support on
      the mental health of disabled war veterans alongside the role of physical
      disability and deployment type. The second aim of the study was to examine the
      relationship between coping strategies and mental health. METHOD: 85 disabled
      Iranian war veterans participated in this study. All of the participants were
      asked to complete the Medical Outcomes Study (MOS),Social Support Survey, Impact
      of Event-Revised Scale (IES-R), Hospital Anxiety and Depression Scale (HADS), The
      Short Form (SF-36) Health Survey Questionnaire, and Brief COPE Scale. RESULTS:
      The results showed that social support had a significant contribution on the
      mental health of the participants above and beyond the physical disability and
      deployment type. The physical disability also predicted the mental health of
      veterans, but deployment type did not have any significant contribution on mental
      health of the participants. The findings also showed that those veterans who used
      constructive coping strategies had better mental health status. CONCLUSION: The
      findings suggest that after more than twenty years of war, social support still
      plays an important role in the life of Iranian disabled war veterans.

PMID- 22952502
TI  - Evaluation of estimating missed answers in conners adult ADHD rating scale
      (screening version).
AB  - OBJECTIVE: Conners Adult ADHD Rating Scale (CAARS) is among the valid
      questionnaires for evaluating Attention-Deficit/Hyperactivity Disorder in adults.
      The aim of this paper is to evaluate the validity of the estimation of missed
      answers in scoring the screening version of the Conners questionnaire, and to
      extract its principal components. METHOD: This study was performed on 400
      participants. Answer estimation was calculated for each question (assuming the
      answer was missed), and then a Kruskal-Wallis test was performed to evaluate the
      difference between the original answer and its estimation. In the next step,
      principal components of the questionnaire were extracted by means of Principal
      Component Analysis (PCA). Finally the evaluation of differences in the whole
      groups was provided using the Multiple Comparison Procedure (MCP). RESULTS:
      Findings indicated that a significant difference existed between the original and
      estimated answers for some particular questions. However, the results of MCP
      showed that this estimation, when evaluated in the whole group, did not show a
      significant difference with the original value in neither of the questionnaire
      subscales. The results of PCA revealed that there are eight principal components
      in the CAARS questionnaire. CONCLUSION: The obtained results can emphasize the
      fact that this questionnaire is mainly designed for screening purposes, and this
      estimation does not change the results of groups when a question is missed
      randomly. Notwithstanding this finding, more considerations should be paid when
      the missed question is a critical one.

PMID- 22952503
TI  - Serum sodium changes in fluoxetine users at different age groups.
AB  - OBJECTIVE: Fluoxetine, a widely used antidepressant, can affect the serum sodium
      level. The aim of this study was to evaluate and compare changes in the serum
      sodium level of depressive patients taking fluoxetine according to age. METHODS:
      This quasi-experimental study was conducted on 126 patients with depression,
      dividing the patients into two age groups of 15 to 35 years, and above 55 years,
      who referred to psychiatric clinics of the Isfahan University of Medical
      Sciences. Serum sodium level was measured prior to fluoxetine therapy and at the
      first and third week after; adverse symptoms were recorded. Serum sodium level,
      hyponatremia, and other adverse effects were compared between the two age groups.
      RESULTS: There was a significant decrease in serum sodium levels in the older
      patients at the first and third week after the therapy; but the serum sodium
      levels decreased only after the third week of therapy in the younger patients
      (p<0.05). Serum sodium level was significantly lower in older than in younger
      patients at the third week of the therapy (140.8+/-2.26 vs. 135.2+/-2.06;
      p<0.05), and hyponatremia was detected only in the older patients after the first
      and third week of therapy, 4.7% and 15.8%, respectively. CONCLUSIONS: Using
      fluoxetine can decrease serum sodium level, which is more frequent, more severe,
      and more clinically manifested in older than younger patients. Monitoring serum
      sodium level is recommended in early weeks of fluoxetine therapy especially for
      patients older than 55 years of age.

PMID- 22952504
TI  - Trifluoperazine-induced cholestatic jaundice.
AB  - Liver injury occurs with many drugs; therefore, a thorough work up is important
      for establishing the diagnosis. We report a case of trifluoperazine-induced
      cholestatic jaundice. A 44-year old male with schizoaffective disorder developed
      an increase in liver enzymes and jaundice after starting treatment with
      trifluoperazine. Workup for other potential etiologies was negative.

PMID- 22952506
TI  - How to break bad news: physicians' and nurses' attitudes.
AB  - OBJECTIVE: Bad news disclosure is one of the most complex tasks of physicians.
      Recent evidences indicate that patients' and physicians' attitude toward breaking
      bad news has been changed since few years ago. The evidence of breaking bad news
      is different across cultures. The aim of this study is to evaluate the attitude
      of medical staff toward breaking bad news to provide a clinical guideline in
      Iran. METHODS: A descriptive study was conducted during 2008-2009 on a sample of
      100 medical staff (50 physicians and 50 nurses) at Cancer Institute of Imam
      Khomeini hospital. The subjects' demographic characteristics and their attitudes
      toward the manner of revealing the diagnosis were registered in a questionnaire.
      RESULTS: The majority of the physicians (86%, n=43) and nurses (74%, n=37),
      mostly the older and more experienced, tended to reveal the diagnosis to
      patients. Only a few physicians (8%, n=4) had been trained how to disclose bad
      news, which discloused diagnosis more than non trained ones. Physicians and
      nurses preferred to inform the patients about the diagnosis when either the
      patients were alone or in the presence of their spouse respectively. Only a few
      physicians (14%) and nurses (24%) agreed to explain life expectancy to patients.
      CONCLUSION: Compared to past, physicians and nurses are more willing to share
      cancer diagnosis with patients. However, lack of adequate communication skills in
      caregivers, and their concerns about managing patients' emotional reactions
      reduce their tendency to disclose bad news to the patients. Therefore, training
      physicians and nurses to expose bad news to the patients seems to be necessary.

PMID- 22952507
TI  - Structural equation model to predict subjective quality of life: a comparison of
      scales with different numerical anchoring.
AB  - OBJECTIVE: The main aim of the current survey was to evaluate a hypothesized
      model on subjective quality of life (SQOL), and to survey the role of scale
      anchoring on satisfaction and dissatisfaction ratings. METHOD: The sample
      consisted of 456 volunteering students who were randomly assigned in to two
      different conditions, and rated their current overall life (dis)satisfaction and
      their (dis)satisfaction on six different domains of life. Each condition used one
      of the two rating scale formats; the formats differed in anchoring (-5 to +5 and
      0 to 10). In order to find how the six different domains of life combine to
      produce an overall measure of subjective quality of life, a SQOL model was
      designed; and the strength of this hypothesized model of SQOL was examined using
      structural equation modeling. RESULTS: The results of testing for multiple group
      invariance of the hypothesized model indicated a cross-validity for the studied
      model for measuring SQOL. Our results also indicated that comparing the two
      different response formats, only for scores derived from Horizontal (0 to 10)
      response format, all the paths in the model were found to be significant.
      CONCLUSION: The results of the confirmatory factor analysis (CFA) support the
      conclusion that the proposed model of SQOL fit the data well, and is able to
      predict SQOL.

PMID- 22952505
TI  - An overview of pharmacological approaches for management and repair of spinal
      cord injuries.
AB  - Spinal cord injury (SCI) leads to loss of nervous tissue and consequently to
      catastrophic neurological deficits. Up to now there is no definite treatment
      available that restores the loss of function to a degree that an independent life
      can be guaranteed.This justifies the cost of research into the new modalities for
      a treatment of SCIs. In current paper, recent developments and new approaches in
      pharmacological therapy have been reviewed.

PMID- 22952508
TI  - World Health Organization Quality-of-Life Scale (WHOQOL-BREF): Analyses of Their
      Item Response Theory Properties Based on the Graded Responses Model.
AB  - OBJECTIVE: This study has used Item Response Theory (IRT) to examine the
      psychometric properties of Health-Related Quality-of-Life. METHOD: This
      investigation is a descriptive- analytic study. Subjects were 370 undergraduate
      students of nursing and midwifery who were selected from Tabriz University of
      Medical Sciences. All participants were asked to complete the Farsi version of
      WHOQOL-BREF. Samejima's graded response model was used for the analyses. RESULTS:
      The results revealed that the discrimination parameters for all items in the four
      scales were low to moderate. The threshold parameters showed adequate
      representation of the relevant traits from low to the mean trait level. With the
      exception of 15, 18, 24 and 26 items, all other items showed low item information
      function values, and thus relatively high reliability from low trait levels to
      moderate levels. CONCLUSIONS: The results of this study indicate that although
      there was general support for the psychometric properties of the WHOQOL-BREF from
      an IRT perspective, this measure can be further improved. IRT analyses provided
      useful measurement information and demonstrated to be a better methodological
      approach for enhancing our knowledge of the functionality of WHOQOL-BREF.

PMID- 22952509
TI  - Reliability and validity of the persian version of distress tolerance scale.
AB  - OBJECTIVES: This study aims to assess the validity and reliability of the Persian
      version of Simons and Gaher's Distress Tolerance scale(DTS) by administering it
      to nicotine dependent students of Tehran University. METHOD: In a descriptive
      cross-sectional study, 317 nicotine dependent students of Tehran University who
      were selected, using available sampling method, completed DTS, Coping with Stress
      Revised(CS-R), Positive and Negative Affect Scales(PANAS) and Fagerstrom Test
      for Nicotine Dependence(FTND). Data were analyzed using descriptive statistic
      methods and correlation coefficient. RESULTS: The alpha coefficients for
      Tolerance, Absorption, Appraisal and Regulation subscales were 0.75, 0.77, 0.70
      and 0.75, respectively. The test-retest correlation coefficients with two months
      interval for Tolerance, Absorption, Appraisal and Regulation subscales and the
      total scale were 0.71, 0.69, 0.77, 0,73 and 0.79, respectively; all of which were
      statistically significant (p<0.001). The correlation coefficient of DTS with
      problem-focused, emotional-focused, less useful and insufficient coping with
      stress were found to be: 0.213, -0.278, -0.337 and -0.196. In addition, the
      correlation coefficient of DTS with positive emotion, negative emotion and
      smoking-dependency were 0.543, -0.224 and -0.653 which were also significant
      (p<0.05). CONCLUSION: The DTS is valid and reliable and suitable to use for
      assessing distress tolerance.

PMID- 22952510
TI  - A survey of the tardive dyskinesia induced by antipsychotic drugs in patients
      with schizophrenia.
AB  - OBJECTIVE: Tardive Dyskinesia (TD), is one of the important problems of the
      patients with schizophrenia. The emergence of these side effects depends on so
      many factors such as the patients' age and the duration of antipsychotic
      treatment. By discovering new drugs (Atypical), there has been an outstanding
      decrease in the emergence of these side effects. The present study investigates
      the symptoms of TD in the Patients with schizophrenia who were under treatments
      for more than 6 months. METHOD: The sample of this study was 200 Patients with
      schizophrenia of four wards in Razi hospital (two acute and two chronic wards)
      who were hospitalized in the winter of 2006 and were qualified for this study.
      The subjects were 101 males and 99 females who were younger than 60 and had
      received antipsychotic drugs for at least 6 months. After psychiatric interview
      and filling the demographic questionnaire by the patients, the required
      information about the drugs and the intensity of the symptoms was acquired. Then
      clinical and physical examinations of tardive dyskinesia were done. Next, the
      tardive dyskinesia disorders' check list (AIMS) was used. Findings of this cross
      sectional, descriptive study were analyzed by SPSS. RESULTS: There was a high
      ratio of 95% between TD and the age factor (P=0.05). There was no relationship
      between symptoms frequency and duration of treatment (P=0.68). Facial muscles and
      oral zones were mostly involved in T.D disorder (72%). CONCLUSION: No significant
      difference was observed between nine fold symptoms of T.D in patients who were
      using traditional drugs and those who were using the new ones (typical and
      atypical). Findings showed that in the intensity of the symptoms, gender does not
      play a major role.

PMID- 22952511
TI  - Trazodone in methandone induced erectile dysfunction.
AB  - OBJECTIVE: Based on findings of previous studies, those men on Methadone
      Maintenance Therapy (MMT) have a high prevalence of Erectile Dysfunction(ED),
      related to hypogonadism and depression. We conducted this study to evaluate the
      efficacy of Trazodone (an antidepressant which can improve sexual function) on
      this sexual dysfunction. METHOD: A structured interview was administered by the
      clinical staff. The interview contained questions about the subjects' socio
      demographic characteristics, their drug use and sexual behavior. In addition to
      the socio-demographic survey, erectile function was assessed using erectile
      dysfunction (ED) intensity scale. Of the 157 subjects, 95 suffered from ED. The
      subjects were informed about the study. Then, seventy five patients voluntarily
      received 50mg of Trazodone for four days, and the dosage was increased to100 mg
      and maintained for 6 weeks. Fifty five patients who completed the treatment
      course were assessed by ED questionnaire again at the end of study. Statistical
      analysis was performed using Stata 8 software. RESULTS: The prevalence of ED was
      60.5% in our sample. The mean erectile dysfunction (ED) intensity scale was
      12.21, and 16.78 before and after the treatment course respectively. (P<0.05) ED
      severity had no significant relation with age and type of substance dependency
      (P>0.05); but it had a significant relation with duration of Methadone therapy
      and Methadone daily dosage. (p<0.05) CONCLUSION: Trazodone may be effective in
      the treatment of methadone induced ED. Further studies with control groups and
      greater sample sizes are warranted.

PMID- 22952512
TI  - Appendicitis in a patient with psychiatric problem and drug withdrawal symptoms.
AB  - Physical disorders can be seen in psychiatric patients. In addition, a delayed
      diagnosis can cause a serious complication of the physical disorder among such
      patients. In this report, a case of appendicitis in a psychiatric case with drug
      withdrawal symptoms was reported.

PMID- 22952513
TI  - C677T Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism in
      Schizophrenia and Bipolar Disorder: An Association Study in Iranian Population.
AB  - OBJECTIVE: The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism
      C677T is suspected to be a risk factor for psychiatric disorders, but it remains
      inconclusive whether the MTHFR polymorphism C677T is imputed to vulnerability to
      schizophrenia and bipolar disorder. METHOD: We prompted impetus to appraise this
      polymorphism in an Iranian population. Therefore, 90 patients with bipolar
      disorder type I (BID), 66 patients with schizophrenia diagnosed according to DSM
      IV criteria, and 94 unrelated controls with no history of psychiatric disorders
      were recruited for this study. Genotype distribution and allelic frequencies of
      C677T polymorphism were investigated. RESULTS: We found no robust differences
      between patients with BID and schizophrenia with control participants either for
      allele frequencies or genotype distribution of MTHFR C677T polymorphism. However,
      a trend toward an increased risk for T allele was observed in the BID patients
      [with odds ratio (OR) of 1.28(CI 95%: 0.8-1.31), p>0.05]. CONCLUSION: However,
      the present and some previous studies failed to elucidate possible interaction
      between MTHFR C677T polymorphism and vulnerability to schizophrenia and bipolar
      disorder; still some associations have been revealed in performed meta-analyses
      that warrant further studies.

PMID- 22952514
TI  - Comparison of catatonia presentation in patients with schizophrenia and mood
      disorders in lagos, Nigeria.
AB  - OBJECTIVE: To compare the clinical profile and pattern of catatonic symptoms of
      patients with schizophrenia and mood disorder. METHOD: Records of 13,968 patients
      seen between 1983-1985 and 2003-2005 were reviewed for symptoms of catatonia by
      resident doctors in psychiatry. Cases in which the diagnosis were schizophrenia
      or mood disorder were then noted. Socio-demographic and clinical features were
      described for each diagnosis. RESULTS: There were a total of 98 cases with
      catatonia out of the 13,968 case notes reviewed. Schizophrenia accounted for
      82.5% and 53.4% in the two periods, while the proportion associated with mood
      disorders increased from 10% to 20.7%. Male to female ratio was 1.2:1 in
      schizophrenia and 1:3 in mood disorder. Those with schizophrenia were younger and
      with an earlier age of onset of symptoms than those with mood disorders.
      CONCLUSION: Catatonia associated with mood disorder was found to be increasing
      over the years when compared with schizophrenia. Differences were observed in
      socio-demographic characteristics and number of predominant catatonic symptoms.
      Having a separate category for catatonia due to the mood disorders in the current
      diagnostic guidelines (10(th) edition of the International Classification of
      Diseases and the 4(th) edition of the Diagnostic and Statistical Manual) will
      help in better diagnosis of catatonia.

PMID- 22952515
TI  - Psychometric Properties of the Persian Version of the Padua Inventory: Washington
      State University Revision (PI-WSUR).
AB  - OBJECTIVE: The psychometric properties and factor structure of the Persian Padua
      Inventory Washington State University Revision (PI-WSUR), a measure of obsessive-
      compulsive phenomena, was examined in a non-clinical sample of 348 Iranian
      university students. METHOD: The PI-WSUR was translated into Persian, and its
      back translation was controlled by the author inventory. A pilot study based on
      cultural differences was carried out on twenty students. The study subjects
      consisted of 348 university students, and they completed PPI, OCI-R, MOCI, BAI,
      STAI, BDI-II and the demographic inventory. RESULTS: The factor analysis of the
      PI-WSUR, exhibited eight factors similar but not identical with factor structure
      in previous studies. as the eight factors are as follows: contamination
      obsessions; washing compulsions; ordering compulsions; checking compulsions;
      obsessional thoughts to harm self/others; obsessional thoughts about violence;
      obsessional impulses to harm self/others; and obsessional impulses to steal. The
      result also indicated excellent internal consistency (Cronbach alpha= 0.92),
      Spearman split test (0.95) and test- retest (r= 0.77). We assessed the concurrent
      validity of the PPI in relation to the Obsessive Compulsive Inventory-Revised
      (OCI-R), and the Maudsley Obsessive- Compulsive Inventory (MOCI). CONCLUSION: The
      Iranian version of the PI to some extend remains the sound psychometric
      properties of the original version.

PMID- 22952516
TI  - The factor structure of the revised cheek and buss shyness scale in an
      undergraduate university sample.
AB  - OBJECTIVE: The present study examined the psychometric properties of the Persian
      version of the Revised Cheek and Buss Shyness Scale (RCBS) using confirmatory
      factor analysis among (n = 300) college students. METHOD: A total of 300
      undergraduate students participated in this study And completed the Revised Cheek
      and Buss Shyness Scale (RCBS). A confirmatory factor analysis was performed to
      test diagnosis as a unitary construct and to test an earlier-reported two-factor
      model. RESULTS: Results indicated that unidimensional measurement model of the
      RCBS did not provide the best fit for the data. Then three measurement models
      were tested, and the results showed that a two-factor model taking into account
      differences in the direction of item wording provided a satisfactory and
      parsimonious fit to the data. Multi-group confirmatory factor analysis was used
      to better understand the factorial invariance of the scale across genders, and
      indicated that two-factor structure of the RCBS was equivalent across genders.
      Supplementary t-tests revealed no other gender differences on shyness.
      CONCLUSIONS: The results provide initial support for the construct validity of
      the self- report version of the RCBS in college students.

PMID- 22952517
TI  - The effect of social and token economy reinforcements on academic achievement of
      students with intellectual disabilities.
AB  - OBJECTIVE: This study investigates the effect of social and token economy
      reinforcements on academic achievement of 9th grade boy students with
      intellectual disabilities in an experimental science class in Tehran Province.
      METHOD: The method used for this study was experimental by pre-test, post- test
      with a control group. The boy students with intellectual disabilities from three
      junior high schools participated in this study. The sample consisted of thirty,
      9th grade boy students with intellectual disabilities in the selected schools;
      the schools were chosen by the multi-stage cluster method. To measure the
      progress of students in the science class, a teacher made test and the Wechsler
      intelligence test for matching the groups for IQ were used. To ensure validity,
      the content validity criteria depended tests calculated by the Lashe method and
      teachers' perspective were used. The reliability coefficient was obtained by the
      reliability coefficient of related tests; the percent agreement method and the
      obtained data were analyzed using one-way variance analysis and Shefe prosecution
      test. RESULTS: The results showed that there was a significant increase in
      academic achievement of students with intellectual disabilities when using token
      economy than using social reinforcements compared with the control group. Also,
      when using social reinforcements, the academic achievement of students was more
      than the control group. CONCLUSION: Token economy and social reinforcements
      increased the academic achievement of students with intellectual disabilities in
      the science class; and also the effect of token economy reinforcements was more
      than social reinforcements on the subjects.

PMID- 22952518
TI  - Psychological Consequences of Abortion among the Post Abortion Care Seeking Women
      in Tehran.
AB  - OBJECTIVE: Abortion either medical or criminal has distinctive physical, social,
      and psychological side effects. Detecting types and frequent psychological side
      effects of abortion among post abortion care seeking women in Tehran was the main
      objective of the present study. METHOD: 278 women of reproductive age (15-49)
      interviewed as study population. Response rate was 93/8. Data collected through a
      questionnaire with 2 parts meeting broad socio-economic characteristics of the
      respondents and health- related abortion consequences. Tehran hospitals were the
      site of study. RESULTS: The results revealed that at least one-third of the
      respondents have experienced psychological side effects. Depression, worrying
      about not being able to conceive again and abnormal eating behaviors were
      reported as dominant psychological consequences of abortion among the
      respondents. Decreased self-esteem, nightmare, guilt, and regret with 43.7%,
      39.5%, 37.5%, and 33.3% prevalence rates have been placed in the lower status,
      respectively. CONCLUSION: Psychological consequences of abortion have
      considerably been neglected. Several barriers made findings limited. Different
      types of psychological side effects, however, experienced by the study population
      require more intensive attention because of chronic characteristic of
      psychological disorders, and women's health impact on family and population
      health.

PMID- 22952519
TI  - Effect of play therapy on behavioral problems of maladjusted preschool children.
AB  - OBJECTIVE: The present research was conducted to study the effect of play therapy
      on reducing behavioral problems of children with oppositional defiant disorder.
      METHOD: Using multistage cluster sampling, regions 6, 7, and 8 in Tehran were
      selected. Among kindergartens of these areas, 3 kindergartens which were
      supported by the welfare organization were randomly selected. Of all the pre
      school children of these 3 kindergartens, 40 children who could have behavioral
      disorder, according to their teachers and parents, were carefully tested. Of
      them, 16 children who showed severe symptoms of oppositional defiant disorder,
      were selected via the results obtained from the child symptom inventory
      questionnaire (CSI-4), teacher's form, and a researcher-made self-control
      checklist, Then, the subjects were randomly divided into one control and one
      experimental group. This research is quasi-experimental, and is conducted using
      pre-test, post-test, and control group. RESULTS: Values of the calculated F for
      oppositional defiant disorder in control group and experimental group was
      meaningful after fixing the effect of pre-test (P<0/001). Therefore, a meaningful
      difference existed between the means of post-test scores of disobedience disorder
      in the experimental and control groups through the fixed effect of the pre-test
      effect. Comparison of adjusted means of the 2 groups showed that the mean of
      attention-deficit hyperactivity disorder (ADHD) in experimental group was lower
      than control group. Therefore, applying play therapy reduced severity of ADHD in
      those children in experimental group compared to those in control group who did
      not receive such instructions. CONCLUSION: Results of this research demonstrates
      that children's disobedience can be reduced by play therapy.

PMID- 22952520
TI  - The QOL-DASS Model to Estimate Overall Quality of Life and General Subjective
      Health.
AB  - OBJECTIVE: In Order to find how rating the WHOQOL-BREF and DASS scales are
      combined to produce an overall measure of quality of life and satisfaction with
      health rating, a QOL-DASS model was designed; and the strength of this
      hypothesized model was examined using the structural equation modeling. METHOD:
      Participants included a sample of 103 voluntary males who were divided into two
      groups of unhealthy (N=55) and healthy (N=48). To assess satisfaction and
      negative emotions of depression, anxiety and stress among the participants, they
      were asked to fill out the WHOQOL-BREF and The Depression Anxiety Stress Scale
      (DASS-42). RESULTS: Our findings on running the hypothesized model of QOL-DASS
      indicated that the proposed model of QOL-DASS fitted the data well for the both
      healthy and unhealthy groups. CONCLUSION: Our findings with CFA to evaluate the
      hypothesized model of QOL-DASS indicated that the different satisfaction domain
      ratings and the negative emotions of depression, anxiety and stress as the
      observed variables can represent the underlying constructs of general health and
      quality of life on both healthy and unhealthy groups.

PMID- 22952521
TI  - A confirmatory factor analysis of the structure of abbreviated math anxiety
      scale.
AB  - OBJECTIVE: The aim of this study is to explore the confirmatory factor analysis
      results of the Persian adaptation of Abbreviated Math Anxiety Scale (AMAS),
      proposed by Hopko, Mahadevan, Bare & Hunt. METHOD: The validity and reliability
      assessments of the scale were performed on 298 college students chosen randomly
      from Tabriz University in Iran. The confirmatory factor analysis (CFA) was
      carried out to determine the factor structures of the Persian version of AMAS.
      RESULTS: As expected, the two-factor solution provided a better fit to the data
      than a single factor. Moreover, multi-group analyses showed that this two-factor
      structure was invariant across sex. Hence, AMAS provides an equally valid measure
      for use among college students. CONCLUSIONS: Brief AMAS demonstrates adequate
      reliability and validity. The AMAS scores can be used to compare symptoms of math
      anxiety between male and female students. The study both expands and adds support
      to the existing body of math anxiety literature.

PMID- 22952522
TI  - Comparison of early maladaptive schemas and parenting origins in patients with
      opioid abuse and non-abusers.
AB  - OBJECTIVE: The aim of this study was to examine the difference of early
      maladaptive schemas and parenting origins in opioid abusers and non-opioid
      abusers. METHOD: The early maladaptive schemas and parenting origins were
      compared in 56 opioid abusers and 56 non-opioids abusers. Schemas were assessed
      by the Young Schema Questionnaire 3rd (short form); and parenting origins were
      assessed by the Young Parenting Inventory. RESULTS: Data were analyzed by
      multivariate analysis of variance (MANOVA). The analysis showed that the means
      for schemas between opioid abusers and non-opioid abusers were different. Chi
      square test showed that parenting origins were significantly associated with
      their related schemas. CONCLUSION: The early maladaptive schemas and parenting
      origins in opioid abusers were more than non-opioid abusers; and parenting
      origins were related to their Corresponding schemas.

PMID- 22952523
TI  - Association of adult attention deficit/hyperactivity disorder and traffic
      injuries in tabriz - iran.
AB  - OBJECTIVE: Nowadays, it is well known that the attention-deficit/hyperactivity
      disorder (ADHD) is not confined to children and adolescents. Recent data showed
      that a considerable portion of the general adult population may be affected by
      ADHD. On the other hand, the impact of ADHD on driving performance, a major area
      of adult life, has gained enthusiasm. More recent studies revealed an association
      between adult ADHD and undesirable driving problems. This study was performed to
      determine the association between presence of adult ADHD and traffic injuries.
      METHODS: In this case-control study, in a 13 month period, 140 subjects (70
      drivers/riders injured in traffic accidents, and 70 age- and sex-matched non
      traumatic controls) were selected to participate in the study and were placed in
      two groups. Subjects with psychiatric comorbidities were excluded. The Conners'
      Adult ADHD Rating Scale (CAARS) self-report (screening version) was used for
      screening adult ADHD in both groups. Finally, the occurrence of this condition
      was compared between the case and control groups. RESULTS: Sixty- nine males and
      one female were recruited in each group with a mean age of 29.31+/-9.32 (18-61)
      years in the case and 29.03+/-9.07 (range: 18-60) years in the control groups (P
      > 0.05). Previous history of traffic accident was significantly higher in the
      case group (15.7% vs. 4.3%, P=0.024). The mean driving time in a day was also
      significantly higher in the case group. In the case group, the scores of CAARS
      (the ADHD index, ADHD symptoms total, inattentive subscale and
      hyperactive/impulsive subscale) were positive (higher than 70) in 4.3, 10, 7.1
      and 10 percent of patients respectively. Among the controls, the corresponding
      proportions were 4.3, 14.3, 8.6 and 8.6 percent respectively. The two groups were
      comparable for the mentioned rates. CONCLUSION: The results of this study
      revealed no significant association between ADHD and traffic injuries in Tabriz-
      Iran.

PMID- 22952524
TI  - Quality of Life and the Associated Psychological Factors in Caregivers of
      Children with PKU.
AB  - OBJECTIVES: The main objective of this study was to investigate the association
      of psychological factors and life stressors with quality of life in caregivers of
      children with PKU. METHODS: Participants were caregivers of children with PKU who
      were referred to a child and adolescent consultation-liaison psychiatry clinic
      for a clinical follow up. Their demographic characteristics were recorded at
      first. WHOQOL-BREF and Depression-Anxiety-Stress Scale (DASS) were used to assess
      quality of life, depression, anxiety and stress in participants. Data analysis
      was performed using SPSS-11.5 statistical software. RESULTS: A total number of 49
      caregivers were enrolled for the study. The mean age of participants and their
      children were 35.63+/-8.82, and 9.84+/-6.62 respectively. Of the participants,
      59.2% were mothers and 40.8% were fathers. Of the children, 51% were girls and
      49% were boys. According to the results, 57.1, 50.1 and 57.1 percent of the
      participants had mild to severe levels of depression, anxiety and stress scores
      respectively. The most associated factors with quality of life were as follows:
      caregivers' occupation; anxiety; and depression mean scores. CONCLUSION: Results
      of the current study showed that caregivers of children with PKU have lower
      levels of quality of life in comparison with the general population; and the most
      correlated factors with quality of life were the caregivers' occupation
      (especially unemployment), and high levels of depression and anxiety.

PMID- 22952525
TI  - Job stress and burnout syndrome in a sample of rural health workers, behvarzes,
      in tehran, iran.
AB  - OBJECTIVE: In the last 30 years, ever since the PHC network in Iran has been
      established, the job duties of Behvarzes (Mental Health Workers in rural areas)
      have been constantly increasing. The aim of this study was to determine the
      burnout level, mental health status and the severity of occupational stress among
      Behvarzes. METHODS: All Behvarzes (227) working in areas covered by Iran
      University of Medical Sciences were considered for participation in the study.
      Maslach Burnout Inventory, GHQ-12, and Stainmentz questionnaires were used.
      RESULTS: The completed questionnaires were returned by 93% of the subjects. The
      mean score of job stress was in the first percentile (42.8 +/- 27.16). 17.6% of
      the study subjects had moderate to severe level of burnout; 12.3%, 5.3% and 43%
      of the subjects had abnormal scores on emotional exhaustion, depersonalization
      and personal subscales respectively; and 28.3% of the cases were suspected to
      have mental disorders by GHQ. DISCUSSION: In spite of increasing assigned jobs to
      Behvarzes, job stress and burnout are not seriously distressful. Providing more
      desirable personal accomplishment for Behvarzes by reducing job ambiguity/
      conflict, participating in planning new programs, and improving interaction with
      health authorities may help them to overcome their job related pressure and
      increasing workload.

PMID- 22952526
TI  - Prevalence of Parasomnia in School aged Children in Tehran.
AB  - OBJECTIVES: Parasomnias can create sleep disruption; in this article we assessed
      parasomnias in school-aged children in Tehran. METHODS: In spring 2005, a total
      of 6000 sleep questionnaires were distributed to school-aged children in 5
      districts of Tehran (Iran). A modified Pediatrics sleep questionnaire with 34
      questions was used. RESULTS: Parasomnias varied from 0.5% to 5.7% among the
      subjects as follows: 2.7% sleep talking, 0.5% sleepwalking, 5.7% bruxism, 2.3%
      enuresis, and nightmare 4%. A group of children showed parasomnias occasionally-
      this was 13.1% for sleep talking, 1.4% for sleepwalking, 10.6% for bruxism, 3.1%
      for enuresis and 18.4% for nightmares. CONCLUSION: A high proportion of children
      starting school suffer from sleep problems. In many cases this is a temporary,
      developmentally related phenomenon, but in 6% of the children the disorder is
      more serious and may be connected with various stress factors and further
      behavioral disturbances.

PMID- 22952527
TI  - Effect of Education on Prevention of Domestic Violence against Women.
AB  - OBJECTIVE: Family violence, specifically domestic violence, has been identified
      by the medical community as a serious, no remitting epidemic with adverse health
      consequences. World Health Organization(WHO) has stated that violence against
      women is a priority issue in the fields of health and human rights. A quasi
      experimental study were conducted in different faculties of Tehran University of
      Medical Sciences to determine the effect of teaching on prevention of domestic
      violence against female employees. METHODS: Forty four women working in various
      faculties of Tehran University of Medical Sciences in 2004 were selected. A
      designed questionnaire was given to the participants to identify kinds, causes
      and consequences of domestic violence. Then an educational booklet was given to
      subjects. This booklet contained information about kinds, causes and consequences
      of domestic violence and how to manage them. To compare the impact of teaching,
      the same questionnaires were distributed among the subjects after six months. The
      questionnaire was specifically tested for content validity. RESULTS: The results
      indicated that the incidence rate of domestic violence pre test and post test
      education was 5.17%. CONCLUSION: Our study showed that education had no effect on
      domestic violence. Solving problems relating to domestic violence due to cardinal
      roots in short time seems to be impossible and impracticable.

PMID- 22952528
TI  - Effects of Self-monitoring Technique on Inattentive Behaviors of Students with
      Attention Deficit Hyperactivity Disorder.
AB  - Beneficial effects of stimulants on core symptoms of Attention Deficit
      Hyperactivity Disorder (ADHD) have been reported in several studies. Behavioral
      interventions have also been proposed as empirically supported interventions for
      ADHD. Although cognitive-behavioral therapies (CBT) have been criticized for the
      lack of evidence-based data, some studies have indicated the positive effects of
      CBT techniques on children with attention deficit hyperactivity disorder (ADHD).
      This article reports the effects of self-monitoring technique, as a CBT
      technique, on inattentive behaviors of children with ADHD.

PMID- 22952529
TI  - Initial Orientation of Attention towards Emotional Faces in Children with
      Attention Deficit Hyperactivity Disorder.
AB  - OBJECTIVE: Early recognition of negative emotions is considered to be of vital
      importance. It seems that children with attention deficit hyperactivity disorder
      have some difficulties recognizing facial emotional expressions, especially
      negative ones. This study investigated the preference of children with attention
      deficit hyperactivity disorder for negative (angry, sad) facial expressions
      compared to normal children. METHOD: Participants were 35 drug naive boys with
      ADHD, aged between 6-11 years,and 31 matched healthy children. Visual orientation
      data were recorded while participants viewed face pairs (negative-neutral pairs)
      shown for 3000ms. The number of first fixations made to each expression was
      considered as an index of initial orientation. RESULTS: Group comparisons
      revealed no difference between attention deficit hyperactivity disorder group and
      their matched healthy counterparts in initial orientation of attention. A
      tendency towards negative emotions was found within the normal group, while no
      difference was observed between initial allocation of attention toward negative
      and neutral expressions in children with ADHD. CONCLUSION: Children with
      attention deficit hyperactivity disorder do not have significant preference for
      negative facial expressions. In contrast, normal children have a significant
      preference for negative facial emotions rather than neutral faces.

PMID- 22952530
TI  - A Confirmatory Factor Analysis of the Structure of Statistics Anxiety Measure: An
      examination of four alternative models.
AB  - OBJECTIVE: The aim of this study is to explore the confirmatory factor analysis
      results of the Persian adaptation of Statistics Anxiety Measure (SAM), proposed
      by Earp. METHOD: The validity and reliability assessments of the scale were
      performed on 298 college students chosen randomly from Tabriz University in Iran.
      Confirmatory factor analysis (CFA) was carried out to determine the factor
      structures of the Persian adaptation of SAM. RESULTS: As expected, the second
      order model provided a better fit to the data than the three alternative models.
      CONCLUSIONS: Hence, SAM provides an equally valid measure for use among college
      students. The study both expands and adds support to the existing body of math
      anxiety literature.

PMID- 22952531
TI  - The utility of the wisconsin card sorting test in differential diagnosis of
      cognitive disorders in Iranian psychiatric patients and healthy subjects.
AB  - OBJECTIVE: The Wisconsin Test Card Sorting Test (WCST) is a neuropsychological
      test that has been suggested as a more specific test for frontal lobes
      dysfunctions. This study was designed to determine whether WCST is able to
      differentiate between Iranian psychiatric patients with cognitive disorders and
      normal subjects, and whether WCST scores are related to severity of symptoms in
      depressive and schizophrenic patients. METHOD: PARTICIPANTS WERE FOUR GROUPS:
      schizophrenics with positive symptoms (n=25); schizophrenics with negative
      symptoms (n=25); major depressives (n=25); and normal subjects (n=25). All
      subjects were tested individually using WCST. To analyze the data, various
      descriptive statistics, ANOVA, t-test and multiple regression analysis were used.
      RESULTS: Regarding the number of categories (P<0.001) and the rate of
      perseverative errors (P<0.01), according to the results, the normal subjects
      performed significantly better than patient groups on WCST, although the
      differences between patient groups were not significant. Our results also showed
      that greater positive or depressive symptoms were not associated with poorer
      scores on WCST performance. Only the level of severity of negative symptoms
      predicted scores on perseverative errors. CONCLUSION: It is concluded that WCST
      can differentiate Iranian psychiatric patients with cognitive disorders from
      normal subjects, but it is not able to clearly differentiate schizophrenic
      patients with negative symptoms from those with positive symptoms and
      depressives. Only severity of negative symptoms affects WCST performance.

PMID- 22952532
TI  - Help Seeking Process among Children Attending Psychiatry Clinic in Tirana,
      Albania.
AB  - OBJECTIVE: The goal of this study was to investigate all the potential routes to
      Child/Adolescent Psychiatry Clinic-University Hospital Center (CAPC-UHC) in
      Tirana. The article provides demographic data, as well as further information on
      the types and amounts of services children/adolescents received during the
      process of seeking help related to different diagnoses. METHOD: The study was
      conducted in CAPC-UHC in Tirana, during September 2006-September 2007. Data were
      collected from 162 children and their parents using Strengths and Difficulties
      Questionnaire (SDQ) and Pathways Encounter Form. The sample consisted of 53.1%
      (86) males and 46.9% (76) females. The mean age was 9.5+4.4 years. RESULTS: Out
      of the total number of cases that sought care to CAPC; 55, 6% were referred by
      parents themselves, while the rest were referred by others. There was a
      significant effect of gender to intervals from the onset of problem to the first
      career (F=10.803, p=0.001), as well as a significant effect of gender to total
      time intervals from the onset till the specialist of child mental health problem
      (F=6.742, p=0.01). CONCLUSIONS: This is the first study investigating the help
      seeking process to psychiatric care in CAPC Tirana-Albania and may serve as a
      good start in generating evidence based on child/adolescent mental health
      service. Further multicentre studies will enhance the values of the findings,
      since the present study was performed in a single service, and in a setting
      lacking previous works with similar scope that could have served as references.

PMID- 22952533
TI  - Association between physical activity and mental health among high-school
      adolescents in Boushehr province: A population based study.
AB  - OBJECTIVE: Mental health is one of the evaluating factors of community
      indicators, and physical activity is considered an important tool for the
      importance of public health. Previous studies have demonstrated associations
      between physical activity and mental health, but these studies did not include
      those populations in which training children have some traditional and religious
      aspects. METHODS: Multiple logistic regression analyses were used to compare the
      prevalence of mental health among those who had inactive, minimally and HEPA
      activity in a representative sample of adolescents aged 15-19 in South of Iran
      using data from the Mental Health Survey (n=2584). The GHQ-28 and IPAQ-short
      forms were used to evaluate the mental health and physical activity,
      respectively. RESULTS: A total of 2584 adolescents (1401 male and 1178 female)
      participated in the study. The observed odds of psychological symptoms in boys
      compared to girls is 1.2 times (p=0.018). We observed that HEPA-activity
      decreases odds of somatic distress and social dysfunction compared with
      inactivity (p=0.031 and 0.001, respectively); minimally activity decreases odds
      of anxiety compared with inactivity (p=0.038); but physical activity rate was not
      affected on odds of adolescent's depression (p>0.05). CONCLUSION: Physical
      activity decreases mental health subscales except for depression among
      adolescents in Boushehr, southern city of Iran.

PMID- 22952534
TI  - Post partum depression and thyroid function.
AB  - OBJECTIVE: Risk of depression is particularly high for women during the prenatal
      period. Various investigators have attempted to establish a link between thyroid
      function and post partum depression. This study aimed to investigate whether
      thyroid function differs in women with postpartum depression compared to a
      control group. METHODS: In this case-control study, subjects were selected from
      Obstetrics & Gynecology and Psychiatric clinics of Kermanshah University of
      Medical Sciences. Forty eight patients suffering from postpartum depression
      according to Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition totally revised (DSM-IV-TR), and 65 normal controls underwent diagnostic
      evaluation by one trained psychiatrist using Structured Clinical Interview for
      DSM-IV-TR. Then, the demographic questionnaire and the Persian version of
      Edinburgh Postnatal Depression Scale (EPDS) were completed by the participants.
      Finally, their thyroid functions were assessed. Data analyses were done using the
      SPSS program 13. RESULTS: No statistically significant differences were observed
      between thyroid function tests and postpartum depression. According to multiple
      regression analysis with stepwise method, subjects with lower serum TSH, T3RU, T3
      levels, younger age and longer period after delivery tended to have higher EPDS
      scores (P-value=0.008). CONCLUSION: The present study reports that those women
      with postpartum depression had a no greater prevalence of thyroid dysfunction
      than the control subjects. It seems that thyroid dysfunction should be considered
      in women with postpartum depression individually, but the role of thyroid as an
      important cause of this condition is not yet established. This suggests that
      future studies should concentrate on this concept in postpartum depression.

PMID- 22952535
TI  - Comparison of Value System among a Group of Military Prisoners with Controls in
      Tehran.
AB  - OBJECTIVE: Religious values were investigated in a group of Iranian Revolutionary
      Guards in Tehran. METHODS: The sample consisted of official duty troops and
      conscripts who were in prison due to a crime. One hundred thirty seven
      individuals cooperated with us in the project (37 Official personnel and 100
      conscripts). The instruments used included a demographic questionnaire containing
      personal data and the Allport, Vernon and Lindzey's Study of Values Test. Most
      statistical methods used descriptive statistical methods such as frequency, mean,
      tables and t-test. RESULTS: The results showed that religious value was lower in
      the criminal group than the control group (p<.001). DISCUSSION: This study showed
      lower religious value scores in the criminals group, suggesting the possibility
      that lower religious value increases the probability of committing crimes.

PMID- 22952536
TI  - Depression and Anxiety in a Cardiovascular Outpatient Clinic: A descriptive
      study.
AB  - OBJECTIVE: Cardiac diseases are psycho-somatic disorders, and psychological
      aspects play an essential role in their initiation and exacerbation. The aim of
      this study was to gain appropriate knowledge in the epidemiology of co-morbid
      depression and anxiety disorder in cardiovascular outpatients. METHOD: This study
      is descriptive with a sample of patients attending a cardio-vascular clinic. 238
      individuals were included in this study using a consecutive sampling method. The
      study instrument was Hospital Anxiety and Depression Scale (HADS) questionnaire,
      which is a clinical scale for assessing anxiety and depression. RESULTS: Of the
      238 participants in this study, 93(38.7%) were male and 146 (61.3%) female. 28.5%
      of patients suffered from anxiety disorders, and 41.9% had depression. Regarding
      comorbid diseases such as diabetes mellitus, hyperlipidemia and hypertension, the
      severity of depression was just related to hypertension. There was a meaningful
      relationship between gender and symptoms of anxiety so that symptoms were more
      severe in women. CONCLUSION: Considering the high prevalence of depression and
      anxiety in patients suffering from cardio-vascular diseases, it is necessary to
      screen psychological disorders in patients with cardio-vascular diseases and
      improve their cardio-vascular health and quality of life as mush as possible.

PMID- 22952537
TI  - Exploratory Factor Analysis of SCL90-R Symptoms Relevant to Psychosis.
AB  - OBJECTIVE: Inconsistent results have been reported regarding the symptom
      dimensions relevant to psychosis in symptoms check list revised (SCL90-R), i.e.,
      "psychoticism" and "paranoid ideation". Therefore, some studies have suggested
      different factor structures for questions of these two dimensions, and proposed
      two newly defined dimensions of "schizotypal signs" and "schizophrenia nuclear
      symptoms". We conducted an exploratory factor analysis on the items of these two
      dimensions in a general population sample in Iran. METHOD: A total of 2158
      subjects residing in Southern Tehran (capital of Iran) were interviewed using the
      psychoticism and paranoid ideation questions in SCL90-R to assess severity of
      these symptom dimensions. Factor analysis was done through SAS 9.1.3 PROC FACTOR
      using Promax rotation (power=3) on the matrix of "polychoric correlations among
      variables" as the input data. RESULTS: Two factors were retained by the
      proportion criterion. Considering loadings >= 0.5 as minimum criteria for factor
      loadings, 7 out of 10 questions from psychoticism, and 3 out of 6 questions from
      paranoid ideation were retained, and others were eliminated. The factor labels
      proposed by the questionnaire suited the extracted factors and were retained.
      Internal consistency for each of the dimensions was acceptable (Cronbach's alpha
      0.7 and 0.74 for paranoid ideation and psychoticism respectively). Composite
      scores showed a half-normal distribution for both dimensions which is predictable
      for instruments that detect psychotic symptoms. CONCLUSION: Results were in
      contrast with similar studies, and questioned them by suggesting a different
      factor structure obtained from a statistically large population. The population
      in a developing nation (Iran) in this study and the socio-cultural differences in
      developed settings are the potential sources for discrepancies between this
      analysis and previous reports.

PMID- 22952538
TI  - Structural Changes in the Insular Cortex in Alcohol Dependence: A cross sectional
      study.
AB  - OBJECTIVE: This study was conducted to determine the changes in the insular
      cortex in alcohol dependent subjects, and to compare the same with controls, the
      associated clinical findings. METHODS: The study group consisted of 30 subjects
      with alcohol dependence syndrome (ADS) selected randomly from the out patient
      services of the department of psychiatry of a tertiary care hospital. The control
      group consisted of 30 matched subjects selected randomly from the out patient
      department and from patients screened for uncomplicated headache. Both groups
      were examined by a computerized scan (CT), and Mini Mental Status Examination
      (MMSE). RESULTS: Chi square, and 't' test were done after calculating the Evan's
      ratio. The two groups were compared to assess the cortical atrophy and
      ventricular enlargement. Cognitive functions were tested by MMSE, and the scores
      were compared. Atrophy was significantly higher in the experimental group;
      however, it was not significant. Cognitive functioning was found to be
      significantly impaired in the experimental group. DISCUSSION: The study showed
      that alcohol dependence leads to cortical atrophy which is age independent. The
      statistically significant disturbance in the MMSE scores along with the frontal
      and parietal cortical atrophy is also indicative of the insular cortex
      involvement in the experimental group. CONCLUSION: Alcohol dependence leads to
      cerebral atrophy along with the involvement of the insular cortex.

PMID- 22952539
TI  - Effect of cognitive processing therapy and holographic reprocessing on reduction
      of posttraumatic cognitions in students exposed to trauma.
AB  - OBJECTIVE: This research was conducted to examine the effect of cognitive
      processing therapy and holographic reprocessing on the reduction of posttraumatic
      cognitions in students exposed to trauma. METHOD: This was an experimental study
      with spread pretest-posttest randomized groups design. Statistical society of
      this research consisted of male freshman, junior and senior high school students
      of Uremia (N=10286). Utilizing Traumatic Events Screening Inventory, and SCL-90 R
      on 1000 randomly selected high school students, 129 students were recognized as
      having experienced traumatic events. Of the subjects, 60 were selected randomly.
      Then, clinical interview was conducted, and the selected sample was randomly
      assigned in to three groups of cognitive processing therapy, holographic
      reprocessing and control. These groups responded to Posttraumatic Cognitions
      Inventory in pretest and post test. Differences of pre-post test scores were
      analyzed using one way ANOVA and Scheffe test. RESULTS: The results demonstrated
      significant differences between the three groups in total score of the
      Posttraumatic Cognition Inventory. Difference was also observed in negative
      cognitions on self and self-blame dimensions. Furthermore, these two therapeutic
      methods were equally effective in the reduction of posttraumatic cognitions.
      CONCLUSION: It appears that cognitive processing therapy and holographic
      reprocessing which had been originally developed and tested for sexually
      assaulted females, can also be applied for the victims of other traumatic events,
      particularly adolescents.

PMID- 22952540
TI  - Resiliency and religious orientation: factors contributing to posttraumatic
      growth in Iranian subjects.
AB  - OBJECTIVE: This study investigated the relationship between resilience and
      religious orientation (internal and external) with posttraumatic growth (PTG).
      This study also examined the impact of marriage and sex variables on growth.
      METHOD: Participants were selected based on prescreening of a larger group of
      students enrolled in the University of Shiraz. Participants were recruited in two
      stages. Three hundred fifty students were randomly selected in the first stage,
      and those students who experienced a minimum of one traumatic event within the
      last five years were selected in the second stage. They completed the Traumatic
      Life Event Questionnaire (TLEQ), the Posttraumatic Growth Inventory-Iranian
      version (PTGI-I), and the Religious Orientation Scale (ROS). RESULTS: According
      to stepwise regression analysis, two subscales of resiliency, novelty seeking and
      positive future orientation, and a subscale of religious orientation, intrinsic
      orientation, were related to PTG. In addition, compared to singles, the married
      subjects experienced greater degree of growth. Personal extrinsic orientation and
      emotional regulation factor of resilience had a positive and meaningful
      relationship with PTG, although they were omitted from the regression analysis
      model. Sex and Socio-Extrinsic religious orientation were not related to PTG.
      CONCLUSION: Some subscales of resiliency and religious orientation could predict
      posttraumatic growth in Iranian subjects, but there were no gender differences.
      The intrinsic orientation had the greatest significance in predicting
      posttraumatic growth. The personal extrinsic orientation had a significant
      positive correlation with post-traumatic growth, no significant correlation was
      observed between social extrinsic orientation and post-traumatic growth. The
      openness to experience was an important feature for proper growth of people
      facing a trauma. Optimistic subjects showed more flexibility in their coping
      strategies, and therefore had a tendency to adapt themselves to problematic
      situations.

PMID- 22952541
TI  - Effective Factors in Enhancing School Manager's Job Motivation.
AB  - OBJECTIVE: This study examines the effective factors in enhancing school
      manager's job motivation from viewpoint of school mangers, teachers, education
      department managerial and staff experts in teaching, and also identifies and
      prioritizes each of these factors and indicators. METHOD: For selecting a
      representative sample and increasing measurement precision, 587 people were
      selected using classified random sampling. The measurement tool was a 79
      questionnaire made by the researcher. The questionnaire was collected using
      motivation theories and observing the findings of previous researches. Then,
      according to the three-stage Delphi technique, the questionnaire was sent to
      experts in education. The reliability of instruments was measured by calculating
      Cronbach's Alpha coefficient, and total reliability of the test was 0.99; the
      validity of the instrument was assessed by factor analysis (Construct Validity)
      and its load factor was 0.4 which was high. RESULTS: The results from factor
      analysis shows that the effective factors in enhancing manager's job motivation
      are as follows: self- actualization (51%) including 28 indices; social factor
      (7/9%) including 22 indices; self-esteem (3.2%) including 17 indices; job
      desirable features (2.2%) including 4 indices; physiologic (1.8%) including 4
      indices; and job richness (1.6%) including 4 indices. CONCLUSIONS: The results
      show that the six mentioned factors determine 68% of the total variance of
      manager's motivation.

PMID- 22952542
TI  - Mini Mental State Examination (MMSE) in First Episode of Psychosis.
AB  - OBJECTIVE: Neurocognitive deficits are now recognized as part of the fundamental
      disturbances and are a major determinant of functional outcome in psychosis. A
      cross-sectional association between cognitive deficits and poor social and
      occupational outcomes has been demonstrated; and treatment of cognitive
      impairment at the time of the first episode may have the potential to change
      functional outcomes of the illness. We conducted this study to evaluate cognitive
      function in first episode of psychosis by the Mini Mental State Examination
      (MMSE). METHOD: Sixty two patients with first episode of psychosis were selected
      and underwent psychiatric interview and took MMSE test. Statistical analysis was
      done using SPSS-18 software. RESULTS: According to MMSE scale, 47 patients
      (75.8%) showed definite cognitive impairment, 8(12.9%) showed possible
      impairment, and 7(11.3%) showed no cognitive impairment. According to MMSE
      subscale, registration (69.4%) and recall (77.3%) were the most impaired
      cognitive areas. CONCLUSIONS: The results of the current study indicate
      significant cognitive impairment in patients with first episode of psychosis. We
      recommend future studies with larger sample size and control group for further
      evaluation of cognitive function as early treatment of cognitive impairments may
      have important implications in the course of illness.

PMID- 22952543
TI  - Treatment of Visual Hallucinations in Schizophrenia by Acetylcholinesterase
      Inhibitors: a case report.
AB  - Schizophrenia and various neurological disorders have some signs and symptoms.
      Visual hallucinations are one of such disorders. The related studies in some
      diseases for example Parkinson Disease and Lewy Body Dementia indicate that
      Acetylcholine (Ach) plays a significant role in neuropsychiatric manifestation
      and its association with visual hallucination; therefore, visual hallucinations
      occur due to the depletion of Ach. Drug therapies such as Cholinesterase
      inhibitors (ChEIs) for increasing Ach level may be beneficial in treating visual
      hallucination. AchEI's have been used in the treatment of visual hallucinations
      in Dementia and Parkinson's Disease. We thought that a similar Ach depletion may
      cause visual hallucinations in patients with schizophrenia and may provide a
      target for drug treatment. We had a patient with schizophrenia whose psychotic
      symptoms responded to the treatment plan, but her visual hallucination did not.
      However, the patient's visual hallucination successfully responded to
      Rivastigmine (AchEI).This case illustrates the use of an AchEI in the treatment
      of refractory visual hallucinations in a patient with schizophrenia.

PMID- 22952544
TI  - Abstracts of 28th annual congress of Iranian psychiatric association: tehran,
      november 15-17, 2011.

PMID- 22952545
TI  - Delayed face recognition in children and adolescents with autism spectrum
      disorders.
AB  - OBJECTIVE: Children with autism spectrum disorders (ASDs) have great problems in
      social interactions including face recognition. There are many studies reporting
      deficits in face memory in individuals with ASDs. On the other hand, some studies
      indicate that this kind of memory is intact in this group. In the present study,
      delayed face recognition has been investigated in children and adolescents with
      ASDs compared to the age and sex matched typically developing group. METHODS: In
      two sessions, Benton Facial Recognition Test was administered to 15 children and
      adolescents with ASDs (high functioning autism and Asperger syndrome) and to 15
      normal participants, ages 8-17 years. In the first condition, the long form of
      Benton Facial Recognition Test was used without any delay. In the second session,
      this test was administered with 15 seconds delay after one week. The reaction
      times and correct responses were measured in both conditions as the dependent
      variables. RESULTS: Comparison of the reaction times and correct responses in the
      two groups revealed no significant difference in delayed and non-delayed
      conditions. Furthermore, no significant difference was observed between the two
      conditions in ASDs patients when comparing the variables. Although a significant
      correlation (p<0.05) was found between delayed and non-delayed conditions, it was
      not significant in the normal group. Moreover, data analysis revealed no
      significant difference between the two groups in the two conditions when the IQ
      was considered as covariate. CONCLUSION: In this study, it was found that the
      ability to recognize faces in simultaneous and delayed conditions is similar
      between adolescents with ASDs and their normal counterparts.

PMID- 22952546
TI  - Parenting Self Efficacy in Mothers of Children with Attention Deficit
      Hyperactivity Disorder vs. Normal Children.
AB  - OBJECTIVES: The main purpose of this study was to compare parenting self efficacy
      between mothers of children with attention deficit-hyperactivity disorder (ADHD)
      and mothers of normal children. METHOD: One hundred twenty mothers including 60
      mothers of children with ADHD and 62 mothers of normal children were selected. In
      each group the participants were allocated between three subgroups of preschool,
      first and second grade of primary school. The participants were evaluated for
      ADHD symptom severity and parenting self efficacy, using Conner's Parents Rating
      Scales-Revised Short (CPRS-R:S) and Berkeley Parenting Self-efficacy scale. Data
      were analyzed using independent sample T test, Chi square, Pearson and Spearman
      correlation and stepwise linear regression statistical analysis when appropriate.
      RESULTS: The results of this study did not show any significant difference
      between self efficiency in mothers of children with ADHD and mothers of normal
      children in preschool and first grade of primary school. However, between group
      differences were significant in mothers of children in second grade of primary
      school. The most associated factors with parenting self efficacy were Children's
      age, and education level. CONCLUSION: No difference was observed in self efficacy
      of parents of ADHD children and parents of normal children in pre-school and
      first grade of primary school. However, parenting self efficacy was significantly
      lower in parents of the second grade ADHD children compared to the normal group.
      Increment in age and education level of children with ADHD may be associated with
      lower level of parenting self efficacy.

PMID- 22952547
TI  - Comparison Of Prevalence Of Postpartum Depression Symptoms Between Breastfeeding
      Mothers And Non-breastfeeding Mothers.
AB  - OBJECTIVES: There is a relationship between infant feeding method and maternal
      postpartum depression (PPD). This study was carried out in an Iranian population
      to compare the prevalence of PPD symptoms between breast feeding and non-breast
      feeding mothers for first time. METHODS: Four health centers in Ahvas were
      selected by random sampling in 2009. At first 78 non-breast feeding mothers at
      two months postpartum were recruited in the study and then 78 breast feeding
      mothers were recruited through random sampling. They were re-assessed in six
      months postpartum period. Demographic and obstetric data questionnaire and
      Edinburgh Postnatal Depression Scale (EPDS) were used. RESULTS: There was a
      significant difference in prevalence of Edinburgh Postnatal Depression Scale
      positive between breast feeding (2.5%) and non-breast feeding mothers (19.4%) (p
      = 0.004). CONCLUSION: Infant feeding method may be related to maternal mood
      disorder and breast feeding mothers are less depressed. Breastfeeding may
      decrease PPD.

PMID- 22952548
TI  - Estimates of Self, Parental and Partner Multiple Intelligences in Iran: A
      replication and extension.
AB  - Two hundred and fifty-eight Iranian university students estimated their own,
      parents', and partners' overall (general) intelligence, and also estimated 13
      'multiple intelligences' on a simple, two-page questionnaire which was previously
      used in many similar studies. In accordance with previous research, men rated
      themselves higher than women on logical-mathematical, spatial and musical
      intelligence. There were, however, no sex differences in ratings of parental and
      partner multiple intelligences, which is inconsistent with the extant literature.
      Participants also believed that they were more intelligent than their parents and
      partners, and that their fathers were more intelligent than their mothers.
      Multiple regressions indicated that participants' Big Five personality typologies
      and test experience were significant predictors of self-estimated intelligence.
      These results are discussed in terms of the cross-cultural literature in the
      field. Implications of the results are also considered.

PMID- 22952549
TI  - Exploratory and confirmatory factor analysis of the career decision-making
      difficulties questionnaire.
AB  - OBJECTIVE: The present study aimed at validating the structure of Career Decision
      making Difficulties Questionnaire (CDDQ). METHODS: Five hundred and eleven
      undergraduate students took part in this research; from these participants, 63
      males and 200 females took part in the first study, and 63 males and 185 females
      completed the survey for the second study. RESULTS: The results of exploratory
      factor analysis (EFA) indicated strong support for the three-factor structure,
      consisting of lack of information about the self, inconsistent information, lack
      of information and lack of readiness factors. A confirmatory factor analysis was
      run with the second sample using structural equation modeling. As expected, the
      three-factor solution provided a better fit to the data than the alternative
      models. CONCLUSION: CDDQ was recommended to be used for college students in this
      study due to the fact that this instrument measures all three aspects of the
      model. Future research is needed to learn whether this model would fit other
      different samples.

PMID- 22952550
TI  - Basic religious beliefs and personality traits.
AB  - OBJECTIVE: Spiritual beliefs can help people find meaning of life, and can also
      influence their feelings, behaviors and mental health. The present research
      studied the relationship between basic religious beliefs (Human, Existence and
      God) and five personality factors: neuroticism, extraversion, openness,
      agreeableness, conscientiousness. METHOD: One hundred seventy eight students of
      Islamic Azad University in Torbat-jam were randomly selected and completed the
      basic religious beliefs and NEO Questionnaires. RESULTS: Data showed that basic
      religious beliefs have a significant negative correlation with neuroticism (r=
      0.29),and a significant positive relationship with
      extraversion(r=0.28),openness(r=0.14),agreeableness (r=0.29),and
      conscientiousness (r=0.48). Also, the results of the regression analysis showed
      that basic religious beliefs can anticipate neuroticism, extraversion,
      agreeableness and conscientiousness, but they cannot anticipate the openness
      factor significantly. CONCLUSION: The findings of this study demonstrate that
      basic religious beliefs have a positive relationship with good characteristics
      that help people resolve the challenges of their lives and identity crisis. Thus,
      the results of this study support the idea of Religious Cognitive-Emotional
      Theory that religiosity is correlated with positive personality traits.

PMID- 22952551
TI  - Melatonin effects in methylphenidate treated children with attention deficit
      hyperactivity disorder: a randomized double blind clinical trial.
AB  - OBJECTIVE: The aim of this study was to determine melatonin effects on sleep
      patterns, symptoms of hyperactivity and attention deficiency in children with
      attention-deficit hyperactivity disorder (ADHD). METHODS: Children with age range
      of 7-12 years who had a combined form of ADHD were randomly divided in to 2
      groups according to gender blocks. One group took melatonin (3 or 6mg) combined
      with methylphenidate (Ritalin) (1mg/kg), and the other group took placebo
      combined with methylphenidate (1mg/kg). ADHD rating scale and sleep patterns
      questionnaires were completed. Research hypotheses were assessed at the baseline,
      the second, fourth and eighth weeks after the treatment. RESULTS: The mean sleep
      latency and total sleep disturbance scores were reduced in melatonin group, while
      the scores increased in the placebo group (p>=0.05). Data analysis, using ANOVA
      with repeated measures, did not show any statistically significant differences
      between the two groups in ADHD scores. CONCLUSION: Administration of melatonin
      along with methylphenidate can partially improve symptoms of sleep disturbance.
      However, it does not seem to reduce attention deficiency and hyperactivity
      behavior of children with ADHD.

PMID- 22952552
TI  - Attentional Bias towards Emotional Scenes in Boys with Attention Deficit
      Hyperactivity Disorder.
AB  - OBJECTIVE: Children with attention-deficit/hyperactivity disorder (ADHD) react
      explosively and inappropriately to emotional stimuli. It could be hypothesized
      that these children have some impairment in attending to emotional cues. Based on
      this hypothesis, we conducted this study to evaluate visual directions of
      children with ADHD towards paired emotional scenes. METHOD: Thirty boys between
      the ages of 6 and 11 years diagnosed with ADHD were compared with 30 age-matched
      normal boys. All participants were presented paired emotional and neutral scenes
      in the four following categories: pleasant-neutral; pleasant-unpleasant;
      unpleasant-neutral; and neutral - neutral. Meanwhile, their visual orientations
      towards these pictures were evaluated using the eye tracking system. The number
      and duration of first fixation and duration of first gaze were compared between
      the two groups using the MANOVA analysis. The performance of each group in
      different categories was also analyzed using the Friedman test. RESULTS: With
      regards to duration of first gaze, which is the time taken to fixate on a picture
      before moving to another picture, ADHD children spent less time on pleasant
      pictures compared to normal group, while they were looking at pleasant - neutral
      and unpleasant - pleasant pairs. The duration of first gaze on unpleasant
      pictures was higher while children with ADHD were looking at unpleasant - neutral
      pairs (P<0.01). CONCLUSION: Based on the findings of this study it could be
      concluded that children with ADHD attend to unpleasant conditions more than
      normal children which leads to their emotional reactivity.

PMID- 22952553
TI  - Neuronavigation: principles, clinical applications and potential pitfalls.
AB  - Localization of brain lesions and prevention of damage to vital structures are
      important in operation of brain pathologies. Despite development of many
      techniques including angiography, MRI, sonography, and frame base stereotaxy, a
      more accurate localizing technique is still needed (1, 2). A step forward to
      achieve this goal is to develop a navigation system. In this manuscript, we
      explained some clinical applications, advantages, and disadvantages of navigation
      system and tried to have a short glimpse on its future.

PMID- 22952555
TI  - Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage
      in Animal Model of Vascular Dementia.
AB  - Nowadays, the preventive strategy of vascular dementia, one of the challenge
      problems of elderly, has received attention due to the limitation of therapeutic
      efficacy. In this study, we aimed to determine the protective effect and possible
      mechanism of action of mulberry fruit extract on memory impairment and brain
      damage in animal model of vascular dementia. Male Wistar rats, weighing 300-350
      g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period
      of 7 days before and 21 days after the occlusion of right middle cerebral artery
      (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO
      showed the enhanced memory, the increased densities of neuron, cholinergic
      neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress
      in hippocampus. Taken all data together, the cognitive enhancing effect of
      mulberry fruit extract observed in this study might be partly associated with the
      increased cholinergic function and its neuroprotective effect in turn occurs
      partly via the decreased oxidative stress and apoptosis. Therefore, mulberry
      fruit is the potential natural cognitive enhancer and neuroprotectant. However,
      further researches are essential to elucidate the possible active ingredient.

PMID- 22952556
TI  - Bone Micro-CT Assessments in an Orchidectomised Rat Model Supplemented with
      Eurycoma longifolia.
AB  - Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the
      potential to treat osteoporosis in elderly male. This study aimed to determine
      the effects of Eurycoma longifolia supplementation on the trabecular bone
      microarchitecture of orchidectomised rats (androgen-deficient osteoporosis
      model). Forty-eight-aged (10-12 months old) Sprague Dawley rats were divided into
      six groups of sham-operated (SHAM), orchidectomised control (ORX),
      orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised +
      Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60
      mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were
      euthanized following six weeks of treatment. The left femora were used to measure
      the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly
      decreased connectivity density, trabecular bone volume, and trabecular number
      compared to the SHAM group. Testosterone replacement reversed all the
      orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg
      rat worsened the trabecular bone connectivity density and trabecular separation
      parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume.
      High dose of EL (90 mg/kg) may have potential in preserving the bone
      microarchitecture of orchidectomised rats, but lower doses may further worsen the
      osteoporotic changes.

PMID- 22952554
TI  - Molecular signature in HCV-positive lymphomas.
AB  - Hepatitis C virus (HCV) is a positive, single-stranded RNA virus, which has been
      associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL).
      Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL
      development. The underlying molecular signature associated to HCV-related B-NHL
      has to date remained obscure. In this review, we discuss the recent developments
      in this field with a special mention to different sets of genes whose expression
      is associated with BCR coupled to Blys signaling which in turn was found to be
      linked to B-cell maturation stages and NF-kappab transcription factor. Even if
      recent progress on HCV-B-NHL signature has been made, the precise relationship
      between HCV and lymphoma development and phenotype signature remain to be
      clarified.

PMID- 22952557
TI  - Rutin, a Flavonoid That Is a Main Component of Saussurea involucrata, Attenuates
      the Senescence Effect in D-Galactose Aging Mouse Model.
AB  - Saussurea involucrata (Kar. et Kir.), known as the snow lotus, grows in the Tian
      Shan and A'er Tai areas of China. It has recently been reported that the ethyl
      acetate extract of S. involucrata (SI-2) can inhibit proliferation and induce
      apoptosis in PC-3 human prostate cancer cells. This study investigated the
      protective effect of ethyl acetate extract of S. involucrata (SI-2) or rutin, a
      flavonoid extracted from ethyl acetate extract of S. involucrata (SI-2), on D
      galactose- (D-gal-) induced brain injury in mice. Administering SI-2 or rutin (30
      mg/kg/d and 30 mg/kg/d) for 6 weeks, concomitant with D-gal injection,
      significantly increased superoxide dismutase and glutathione peroxidase
      activities and decreased the MDA level in plasma. Furthermore, the result showed
      that the percentages of cleaved caspase-3 and PARP in the D-gal-treated mice were
      much higher than those in the control. Pretreatment using SI-2 or rutin decreased
      the expression of cyclooxygenase-2 via downregulation of NF-kappaB, resulting in
      a decrease in lipid peroxidation. Furthermore, our results also showed that oral
      administration of rutin to these mice significantly improved behavioral
      performance in a step-through passive avoidance task and these results suggest
      that SI-2 or rutin exerts potent antiaging effects on D-gal in mice via
      antioxidative mechanisms.

PMID- 22952558
TI  - Computerized segmentation and characterization of breast lesions in dynamic
      contrast-enhanced MR images using fuzzy c-means clustering and snake algorithm.
AB  - This paper presents a novel two-step approach that incorporates fuzzy c-means
      (FCMs) clustering and gradient vector flow (GVF) snake algorithm for lesions
      contour segmentation on breast magnetic resonance imaging (BMRI). Manual
      delineation of the lesions by expert MR radiologists was taken as a reference
      standard in evaluating the computerized segmentation approach. The proposed
      algorithm was also compared with the FCMs clustering based method. With a
      database of 60 mass-like lesions (22 benign and 38 malignant cases), the proposed
      method demonstrated sufficiently good segmentation performance. The morphological
      and texture features were extracted and used to classify the benign and malignant
      lesions based on the proposed computerized segmentation contour and radiologists'
      delineation, respectively. Features extracted by the computerized
      characterization method were employed to differentiate the lesions with an area
      under the receiver-operating characteristic curve (AUC) of 0.968, in comparison
      with an AUC of 0.914 based on the features extracted from radiologists'
      delineation. The proposed method in current study can assist radiologists to
      delineate and characterize BMRI lesion, such as quantifying morphological and
      texture features and improving the objectivity and efficiency of BMRI
      interpretation with a certain clinical value.

PMID- 22952560
TI  - Haematological changes in HIV infection with correlation to CD4 cell count.
AB  - BACKGROUND: HIV infection is associated with a wide range of haematological
      abnormalities. METHODS AND OBJECTIVES: The objectives in this study were to study
      haematological changes in HIV patients and to correlate them with CD4 cell
      counts. Two hundred and fifty HIV positive patients referred to the haematology
      laboratory section for complete haemogram in whom CD4 count was done were
      included in the study. Haematologic parameters and CD4 counts were studied in
      each of these patients. Descriptive statistics were applied. Association between
      two attributes was calculated by chi-square test and p value less than 0.05 was
      considered statistically significant. RESULTS: Among 250 patients, anaemia was
      seen in 210 (84%) cases. The most common type was normocytic normochromic
      (40.4%). Lymphopenia was seen in 163 (65.2%) cases and thrombocytopenia in 45
      (18%) cases. The majority of cases (70%) had CD4 cell counts below 200
      cells/mm(3). Fifty-four cases (21.6%) had CD4 counts between 200 to 499
      cells/mm(3) and 21 (8.4%) cases had CD4 counts more than 500 cells/ mm(3.) In
      patients with CD4 counts less than 200 cells/mm(3), anaemia was seen in 91.4%
      cases, leucopenia in 26.8% cases, lymphopenia in 80% cases and thrombocytopenia
      in 21.7% cases. CONCLUSION: Haematologic manifestations of HIV infection are
      common and more frequent with progression of disease. The present study revealed
      a significant increase in the number of cases of anaemia, and lymphopenia, with
      decreasing CD4 cell counts. Thrombocytopenia is also seen but does not show
      significant increase with disease progression. The study also highlights the
      importance of simultaneously treating HIV patients for haematologic
      manifestations to reduce morbidity.

PMID- 22952561
TI  - Risk factors for under-nutrition among children aged one to five years in Udupi
      taluk of Karnataka, India: A case control study.
AB  - BACKGROUND: Despite her apparent economic success, India is plagued by a high
      burden of under-nutrition among children under five. This study was aimed at
      understanding some of the risk factors for under-nutrition in a region with
      favourable maternal and child health indicators. METHOD: A case control study was
      carried out among children aged one to five years attending the paediatric
      outpatient department in six rural health care centres in Udupi taluk of
      Karnataka in Southern India. A total of 162 children were included in the study,
      of which 56 were cases. A semi-structured questionnaire was used to interview the
      caregivers of the children and the nutritional status was graded according to the
      Indian Academy of Paediatrics (IAP) grading of protein-energy malnutrition.
      RESULTS: Under-nutrition was associated with illness in the last one month [OR-
      4.78 (CI: 1.83 -12.45)], feeding diluted milk [OR-14.26 (CI: 4.65 - 43.68)] and
      having more than two children with a birth interval <=2 years [OR- 4.93 (CI: 1.78
      - 13.61)]. Lack of exclusive breast feeding, level of education of the caregiver
      and environmental factors like source of water did not have an association.
      CONCLUSION: Childhood illness, short birth interval and consumption of diluted
      milk were some of the significant contributory factors noted among this
      population. Information, Education, Communication (IEC) campaigns alleviating
      food fads and promoting birth spacing is needed.

PMID- 22952559
TI  - An image-based model of the whole human heart with detailed anatomical structure
      and fiber orientation.
AB  - Many heart anatomy models have been developed to study the electrophysiological
      properties of the human heart. However, none of them includes the geometry of the
      whole human heart. In this study, an anatomically detailed mathematical model of
      the human heart was firstly reconstructed from the computed tomography images. In
      the reconstructed model, the atria consisted of atrial muscles, sinoatrial node,
      crista terminalis, pectinate muscles, Bachmann's bundle, intercaval bundles, and
      limbus of the fossa ovalis. The atrioventricular junction included the
      atrioventricular node and atrioventricular ring, and the ventricles had
      ventricular muscles, His bundle, bundle branches, and Purkinje network. The
      epicardial and endocardial myofiber orientations of the ventricles and one layer
      of atrial myofiber orientation were then measured. They were calculated using
      linear interpolation technique and minimum distance algorithm, respectively. To
      the best of our knowledge, this is the first anatomically-detailed human heart
      model with corresponding experimentally measured fibers orientation. In addition,
      the whole heart excitation propagation was simulated using a monodomain model.
      The simulated normal activation sequence agreed well with the published
      experimental findings.

PMID- 22952562
TI  - Contact lens compliance among a group of young, university-based lens users in
      South India.
AB  - PURPOSE: To investigate the rate of compliance with the soft contact lens care
      and maintenance procedures with a focus on contact lens wearing habits, cleaning
      and disinfecting procedures, and maintenance of lens care accessories in a group
      of young, university-based contact lens wearers METHODS: Two hundred and sixteen
      young soft contact lens wearers with an age range of 18-22 years were selected
      conveniently from the student population of Manipal University, Manipal, India.
      After receiving informed consent from the participants, their level of compliance
      with contact lenses was assessed using a questionnaire. RESULTS: The mean (+/-SD)
      age of the participants was 21.86+/-2.35 years. Out of 216 subjects, only 34% of
      the lens users were identified to be compliant with the least level of compliance
      observed in the maintenance of lens care accessories. Conventional users showed
      significantly (p=0.001) better level of compliance compared to disposable wearers
      and so did the users who acquired their lenses from clinicians (p=0.001) compared
      to over-the-counter lens receipt. The gender (p=0.496) and years of experience in
      contact lens use (p=0.142) did not show any statistically significant difference
      in the level of compliance. CONCLUSION: This study demonstrated that non
      compliance with lens care procedures among a group of young, university-based
      soft contact lens wearers is common. The results indicated that all subjects had
      some degree of non-compliance and the least level of compliance observed in the
      care of lens accessories.

PMID- 22952563
TI  - Laryngeal tuberculosis: A case of a non-healing laryngeal lesion.
AB  - We report a case of laryngeal tuberculosis in a 47-year-old Korean man. Laryngeal
      tuberculosis is rare and currently accounts for less than 1% of all cases of
      tuberculosis. Clinical features of laryngeal tuberculosis include hoarseness,
      odynophagia and dyspnoea. Macroscopically, laryngeal tuberculosis may mimic
      laryngeal carcinoma, chronic laryngitis or laryngeal candidiasis. The diagnosis
      is often delayed due to a low index of clinical suspicion and hence may pose a
      significant public health risk. Laryngeal tuberculosis should be considered in
      the differential diagnosis of patients who present with any form of laryngeal
      lesion.

PMID- 22952564
TI  - Left ventricular thrombus in patients with acute myocardial infarction:Case
      report and Caribbean focused update.
AB  - Despite the well documented benefit of echocardiography in acute coronary
      syndromes, its wide-scale use in the Caribbean is limited by access, health
      literacy and affordability. Because of the limited use of echocardiography in the
      region, routine complications of acute myocardial infarction (AMI) are not fully
      appreciated and may go unrecognized, further contributing to increased
      cardiovascular morbidity and mortality. It is therefore necessary to bring focus
      to this common clinical condition and highlight the clinical utility of
      echocardiography in facilitating timely and accurate diagnosis. We report here a
      case of large left ventricular (LV) thrombus in a patient with AMI. Coronary
      angiography showed completely occluded left anterior descending artery (LAD) with
      angiographically normal remaining vessels. Immediate anticoagulation was
      commenced with heparin and overlapped with warfarin. No Primary Angioplasty (PA)
      was done based on the evidence from occluded artery trial. LV thrombus was
      completely resolved on echocardiography at three months. No evidence of thrombo
      embolism was found during the resolution of LV thrombus.

PMID- 22952565
TI  - Possible impact of increase in female medical student admissions in Nepal:
      Findings from a qualitative study among medical undergraduates.
AB  - BACKGROUND: In Nepal, a developing country in South Asia, the number of female
      medical students has increased significantly. AIMS: The present study was carried
      out to explore perceived perceptions for this increase, study the perceived
      impact on teaching-learning activities, medical school infrastructure and
      possible perceived changes in the doctor-patient relationship. METHOD: First,
      second and third year students were invited to participate in focus group
      discussions (FGDs). Fifty-four students were willing to participate. Twenty-five
      were from the first year, 20 from the second and 9 from the third year. The FGDs
      conducted over a 90 minute period were voice and video recorded. The groups
      consisted of both males and females from a particular intake. The findings were
      transcribed verbatim. RESULTS: Participants felt more female students were taking
      up medicine in the country because of more colleges opening in the cities and
      towns making it easier for female students to enrol in the course. Also parents
      consider medicine as a safe, noble and dignified profession for their daughters.
      Participants suggested women are more empathetic doctors and the doctor-patient
      relationship might become more patient-focused. Women doctors can serve as a
      source of inspiration and the overall impact on Nepal would be positive.
      CONCLUSION: Participating students perceived the increasing number of female
      medical students may be due to changes in Nepalese society. This study was
      carried out only among three batches of students in a single medical school.
      Further studies among different batches of students and among interns in other
      medical schools are required. Studies among postgraduate students and doctors are
      also needed.

PMID- 22952567
TI  - Retraction: Comparative expression profile of miRNA and mRNA in primary
      peripheral blood mononuclear cells infected with human immunodeficiency virus
      (HIV-1).

PMID- 22952566
TI  - Assessing the quality, suitability and readability of internet-based health
      information about warfarin for patients.
AB  - BACKGROUND: Warfarin is a high-risk medication where patient information may be
      critical to help ensure safe and effective treatment. Considering the time
      constraints of healthcare providers, the internet can be an important
      supplementary information resource for patients prescribed warfarin. The
      usefulness of internet-based patient information is often limited by challenges
      associated with finding valid and reliable health information. Given patients'
      increasing access of the internet for information, this study investigated the
      quality, suitability and readability of patient information about warfarin
      presented on the internet. METHOD: Previously validated tools were used to
      evaluate the quality, suitability and readability of patient information about
      warfarin on selected websites. RESULTS: The initial search yielded 200 websites,
      of which 11 fit selection criteria, comprising seven non-commercial and four
      commercial websites. Regarding quality, most of the non-commercial sites (six out
      of seven) scored at least an 'adequate' score. With regard to suitability, 6 of
      the 11 websites (including two of the four commercial sites) attained an
      'adequate' score. It was determined that information on 7 of the 11 sites
      (including two commercial sites) was written at reading grade levels beyond that
      considered representative of the adult patient population with poor literacy
      skills (e.g. school grade 8 or less). CONCLUSION: Despite the overall 'adequate'
      quality and suitability of the internet derived patient information about
      warfarin, the actual usability of such websites may be limited due to their poor
      readability grades, particularly in patients with low literacy skills.

PMID- 22952568
TI  - Identification of a potential susceptibility locus for macular telangiectasia
      type 2.
AB  - Macular Telangiectasia type 2 (MacTel) is a relatively rare macular disease of
      adult onset presenting with distortions in the visual field and leading to
      progressive loss of visual acuity. For the purpose of a gene mapping study,
      several pedigrees were ascertained with multiple affected family members.
      Seventeen families with a total of 71 individuals (including 45 affected or
      possibly affected) were recruited at clinical centers in 7 countries under the
      auspices of the MacTel Project. The disease inheritance was consistent with
      autosomal dominant segregation with reduced penetrance. Genome-wide linkage
      analysis was performed, followed by analysis of recombination breakpoints.
      Linkage analysis identified a single peak with multi-point LOD score of 3.45 on
      chromosome 1 at 1q41-42 under a dominant model. Recombination mapping defined a
      minimal candidate region of 15.6 Mb, from 214.32 (rs1579634; 219.96 cM) to 229.92
      Mb (rs7542797; 235.07 cM), encompassing the 1q41-42 linkage peak. Sanger
      sequencing of the top 14 positional candidates genes under the linkage peak
      revealed no causal variants in these pedigrees.

PMID- 22952569
TI  - X-ray phase nanotomography resolves the 3D human bone ultrastructure.
AB  - Bone strength and failure are increasingly thought to be due to ultrastructural
      properties, such as the morphology of the lacuno-canalicular network, the
      collagen fiber orientation and the mineralization on the nanoscale. However,
      these properties have not been studied in 3D so far. Here we report the
      investigation of the human bone ultrastructure with X-ray phase nanotomography,
      which now provides the required sensitivity, spatial resolution and field of
      view. The 3D organization of the lacuno-canalicular network is studied in detail
      over several cells in osteonal and interstitial tissue. Nanoscale density
      variations are revealed and show that the cement line separating these tissues is
      hypermineralized. Finally, we show that the collagen fibers are organized as a
      twisted plywood structure in 3D.

PMID- 22952570
TI  - Segregation of LIPG, CETP, and GALNT2 mutations in Caucasian families with
      extremely high HDL cholesterol.
AB  - To date, few mutations are described to underlie highly-elevated HDLc levels in
      families. Here we sequenced the coding regions and adjacent sequence of the LIPG,
      CETP, and GALNT2 genes in 171 unrelated Dutch Caucasian probands with HDLc>=90th
      percentile and analyzed segregation of mutations with lipid phenotypes in family
      members. In these probands, mutations were most frequent in LIPG (12.9%) followed
      by GALNT2 (2.3%) and CETP (0.6%). A total of 6 of 10 mutations in these three
      genes were novel (60.0%), and mutations segregated with elevated HDLc in
      families. Interestingly, the LIPG mutations N396S and R476W, which usually result
      in elevated HDLc, were unexpectedly found in 6 probands with low HDLc (i.e.,
      <=10th percentile). However, 5 of these probands also carried mutations in ABCA1,
      LCAT, or LPL. Finally, no CETP and GALNT2 mutations were found in 136 unrelated
      probands with low HDLc. Taken together, we show that rare coding and splicing
      mutations in LIPG, CETP, and GALNT2 are enriched in persons with
      hyperalphalipoproteinemia and segregate with elevated HDLc in families. Moreover,
      LIPG mutations do not overcome low HDLc in individuals with ABCA1 and possibly
      LCAT and LPL mutations, indicating that LIPG affects HDLc levels downstream of
      these proteins.

PMID- 22952571
TI  - Bile acid binding resin improves metabolic control through the induction of
      energy expenditure.
AB  - BACKGROUND: Besides well-established roles of bile acids (BA) in dietary lipid
      absorption and cholesterol homeostasis, it has recently become clear that BA is
      also a biological signaling molecule. We have shown that strategies aimed at
      activating TGR5 by increasing the BA pool size with BA administration may
      constitute a significant therapeutic advance to combat the metabolic syndrome and
      suggest that such strategies are worth testing in a clinical setting. Bile acid
      binding resin (BABR) is known not only to reduce serum cholesterol levels but
      also to improve glucose tolerance and insulin resistance in animal models and
      humans. However, the mechanisms by which BABR affects glucose homeostasis have
      not been established. We investigated how BABR affects glycemic control in diet
      induced obesity models. METHODS AND FINDINGS: We evaluated the metabolic effect
      of BABR by administrating colestimide to animal models for the metabolic
      syndrome. Administration of BABR increased energy expenditure, translating into
      significant weight reduction and insulin sensitization. The metabolic effects of
      BABR coincide with activation of cholesterol and BA synthesis in liver and
      thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur
      despite normal food intake and triglyceride absorption. Administration of BABR
      and BA had similar effects on BA composition and thermogenesis, suggesting that
      they both are mediated via TGR5 activation. CONCLUSION: Our data hence suggest
      that BABR could be useful for the management of the impaired glucose tolerance of
      the metabolic syndrome, since they not only lower cholesterol levels, but also
      reduce obesity and improve insulin resistance.

PMID- 22952572
TI  - Erythrocyte enrichment in hematopoietic progenitor cell cultures based on
      magnetic susceptibility of the hemoglobin.
AB  - Using novel media formulations, it has been demonstrated that human placenta and
      umbilical cord blood-derived CD34+ cells can be expanded and differentiated into
      erythroid cells with high efficiency. However, obtaining mature and functional
      erythrocytes from the immature cell cultures with high purity and in an efficient
      manner remains a significant challenge. A distinguishing feature of a
      reticulocyte and maturing erythrocyte is the increasing concentration of
      hemoglobin and decreasing cell volume that results in increased cell
      magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients,
      under anoxic conditions. Taking advantage of these initial observations, we
      studied a noninvasive (label-free) magnetic separation and analysis process to
      enrich and identify cultured functional erythrocytes. In addition to the magnetic
      cell separation and cell motion analysis in the magnetic field, the cell cultures
      were characterized for cell sedimentation rate, cell volume distributions using
      differential interference microscopy, immunophenotyping (glycophorin A),
      hemoglobin concentration and shear-induced deformability (elongation index, EI,
      by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed
      column high-gradient magnetic separator (HGMS) was used for magnetic separation.
      The magnetically enriched fraction comprised 80% of the maturing cells
      (predominantly reticulocytes) that showed near 70% overlap of EI with the
      reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs.
      The results demonstrate feasibility of label-free magnetic enrichment of
      erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence
      of paramagnetic hemoglobin in the maturing erythrocytes.

PMID- 22952573
TI  - A novel MCPH1 isoform complements the defective chromosome condensation of human
      MCPH1-deficient cells.
AB  - Biallelic mutations in MCPH1 cause primary microcephaly (MCPH) with the cellular
      phenotype of defective chromosome condensation. MCPH1 encodes a multifunctional
      protein that notably is involved in brain development, regulation of chromosome
      condensation, and DNA damage response. In the present studies, we detected that
      MCPH1 encodes several distinct transcripts, including two major forms: full
      length MCPH1 (MCPH1-FL) and a second transcript lacking the six 3' exons
      (MCPH1Deltae9-14). Both variants show comparable tissue-specific expression
      patterns, demonstrate nuclear localization that is mediated independently via
      separate NLS motifs, and are more abundant in certain fetal than adult organs. In
      addition, the expression of either isoform complements the chromosome
      condensation defect found in genetically MCPH1-deficient or MCPH1 siRNA-depleted
      cells, demonstrating a redundancy of both MCPH1 isoforms for the regulation of
      chromosome condensation. Strikingly however, both transcripts are regulated
      antagonistically during cell-cycle progression and there are functional
      differences between the isoforms with regard to the DNA damage response; MCPH1-FL
      localizes to phosphorylated H2AX repair foci following ionizing irradiation,
      while MCPH1Deltae9-14 was evenly distributed in the nucleus. In summary, our
      results demonstrate here that MCPH1 encodes different isoforms that are
      differentially regulated at the transcript level and have different functions at
      the protein level.

PMID- 22952574
TI  - Supporting adherence to antiretroviral therapy with mobile phone reminders:
      results from a cohort in South India.
AB  - BACKGROUND: Adherence is central to the success of antiretroviral therapy.
      Supporting adherence has gained importance in HIV care in many national treatment
      programs. The ubiquity of mobile phones, even in resource-constrained settings,
      has provided an opportunity to utilize an inexpensive, contextually feasible
      technology for adherence support in HIV in these settings. We aimed to assess the
      influence of mobile phone reminders on adherence to antiretroviral therapy in
      South India. Participant experiences with the intervention were also studied.
      This is the first report of such an intervention for antiretroviral adherence
      from India, a country with over 800 million mobile connections. METHODS:  STUDY
      DESIGN: Quasi-experimental cohort study involving 150 HIV-infected individuals
      from Bangalore, India, who were on antiretroviral therapy between April and July
      2010. The intervention: All participants received two types of adherence
      reminders on their mobile phones, (i) an automated interactive voice response
      (IVR) call and (ii) A non-interactive neutral picture short messaging service
      (SMS), once a week for 6 months. Adherence measured by pill count, was assessed
      at study recruitment and at months one, three, six, nine and twelve. Participant
      experiences were assessed at the end of the intervention period. RESULTS: The
      mean age of the participants was 38 years, 27% were female and 90% urban.
      Overall, 3,895 IVRs and 3,073 SMSs were sent to the participants over 6 months.
      Complete case analysis revealed that the proportion of participants with optimal
      adherence increased from 85% to 91% patients during the intervention period, an
      effect that was maintained 6 months after the intervention was discontinued (p =
      0.016). Both, IVR calls and SMS reminders were considered non-intrusive and not a
      threat to privacy. A significantly higher proportion agreed that the IVR was
      helpful compared to the SMS (p<0.001). CONCLUSION: Mobile phone reminders may
      improve medication adherence in HIV infected individuals in this setting, the
      effect of which was found to persist for at least 6 months after cessation of the
      intervention.

PMID- 22952575
TI  - The role of cytochrome c on apoptosis induced by Anagrapha falcifera multiple
      nuclear polyhedrosis virus in insect Spodoptera litura cells.
AB  - There are conflicting reports on the role of cytochrome c during insect
      apoptosis. Our previous studies have showed that cytochrome c released from the
      mitochondria was an early event by western blot analysis and caspase-3 activation
      was closely related to cytochrome c release during apoptosis induced by
      baculovirus in Spodoptera litura cells (Sl-1 cell line). In the present study,
      alteration in mitochondrial morphology was observed by transmission electron
      microscopy, and cytochrome c release from mitochondria in apoptotic Sl-1 cells
      induced with Anagrapha falcifera multiple nuclear polyhedrosis virus (AfMNPV) has
      further been confirmed by immunofluoresence staining protocol, suggesting that
      structural disruption of mitochondria and the release of cytochrome c are
      important events during Lepidoptera insect cell apoptosis. We also used Sl-1 cell
      free extract system and the technique of RNA interference to further investigate
      the role of cytochrome c in apoptotic Sl-1 cells induced by AfMNPV. Caspase-3
      activity in cell-free extracts supplemented with exogenous cytochrome c was
      determined and showed an increase with the extension of incubation time. DsRNA
      mediated silencing of cytochrome c resulted in the inhibition of apoptosis and
      protected the cells from AfMNPV-induced cell death. Silencing of expression of
      cytochrome c had a remarkable effect on pro-caspase-3 and pro-caspase-9
      activation and resulted in the reduction of caspase-3 and caspase-9 activity in
      Sl-1 cells undergoing apoptosis. Caspase-9 inhibitor could inhibit activation of
      pro-caspase-3, and the inhibition of the function of Apaf-1 with FSBA blocked
      apoptosis, hinting that Apaf-1 could be involved in Sl-1 cell apoptosis induced
      by AfMNPV. Taken together, these results strongly demonstrate that cytochrome c
      plays an important role in apoptotic signaling pathways in Lepidopteran insect
      cells.

PMID- 22952576
TI  - Cancer association study of aminoacyl-tRNA synthetase signaling network in
      glioblastoma.
AB  - Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multifunctional proteins
      (AIMPs) exhibit remarkable functional versatility beyond their catalytic
      activities in protein synthesis. Their non-canonical functions have been
      pathologically linked to cancers. Here we described our integrative genome-wide
      analysis of ARSs to show cancer-associated activities in glioblastoma multiforme
      (GBM), the most aggressive malignant primary brain tumor. We first selected 23
      ARS/AIMPs (together referred to as ARSN), 124 cancer-associated druggable target
      genes (DTGs) and 404 protein-protein interactors (PPIs) of ARSs using NCI's
      cancer gene index. 254 GBM affymetrix microarray data in The Cancer Genome Atlas
      (TCGA) were used to identify the probe sets whose expression were most strongly
      correlated with survival (Kaplan-Meier plots versus survival times, log-rank t
      test <0.05). The analysis identified 122 probe sets as survival signatures,
      including 5 of ARSN (VARS, QARS, CARS, NARS, FARS), and 115 of DTGs and PPIs
      (PARD3, RXRB, ATP5C1, HSP90AA1, CD44, THRA, TRAF2, KRT10, MED12, etc). Of note,
      61 survival-related probes were differentially expressed in three different
      prognosis subgroups in GBM patients and showed correlation with established
      prognosis markers such as age and phenotypic molecular signatures. CARS and FARS
      also showed significantly higher association with different molecular networks in
      GBM patients. Taken together, our findings demonstrate evidence for an ARSN
      biology-dominant contribution in the biology of GBM.

PMID- 22952577
TI  - Cyclodextrin inclusion complex to improve physicochemical properties of herbicide
      bentazon: exploring better formulations.
AB  - The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted
      an increase in the development of new formulations. The capacity of these organic
      host structures of including guest within their hydrophobic cavities, improves
      physicochemical properties of the guest. In the case of pesticides, several
      inclusion complexes with cyclodextrins have been reported. However, in order to
      explore rationally new pesticide formulations, it is essential to know the effect
      of cyclodextrins on the properties of guest molecules. In this study, the
      inclusion complexes of bentazon (Btz) with native betaCD and two derivatives, 2
      hydroxypropyl-beta-cyclodextrin (HPCD) and sulfobutylether-beta-cyclodextrin
      (SBECD), were prepared by two methods: kneading and freeze-drying, and their
      characterization was investigated with different analytical techniques including
      Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis
      (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All
      these approaches indicate that Btz forms inclusion complexes with CDs in solution
      and in solid state, with a stoichiometry of 1:1, although some of them are
      obtained in mixtures with free Btz. The calculated association constant of the
      Btz/HPCD complex by DPV was 244+/-19 M(-1) being an intermediate value compared
      with those obtained with betaCD and SBECD. The use of CDs significantly increases
      Btz photostability, and depending on the CDs, decreases the surface tension. The
      results indicated that bentazon forms inclusion complexes with CDs showing
      improved physicochemical properties compared to free bentazon indicating that CDs
      may serve as excipient in herbicide formulations.

PMID- 22952578
TI  - Soluble rank ligand produced by myeloma cells causes generalised bone loss in
      multiple myeloma.
AB  - Patients with multiple myeloma commonly develop focal osteolytic bone disease, as
      well as generalised osteoporosis. The mechanisms underlying the development of
      osteoporosis in patients with myeloma are poorly understood. Although disruption
      of the RANKL/OPG pathway has been shown to underlie formation of focal osteolytic
      lesions, its role in the development of osteoporosis in myeloma remains unclear.
      Increased soluble RANKL in serum from patients with myeloma raises the
      possibility that this molecule plays a key role. The aim of the present study was
      to establish whether sRANKL produced by myeloma cells contributes directly to
      osteoporosis. C57BL/KaLwRij mice were injected with either 5T2MM or 5T33MM murine
      myeloma cells. 5T2MM-bearing mice developed osteolytic bone lesions (p<0.05) with
      increased osteoclast surface (p<0.01) and reduced trabecular bone volume
      (p<0.05). Bone volume was also reduced at sites where 5T2MM cells were not
      present (p<0.05). In 5T2MM-bearing mice soluble mRANKL was increased (p<0.05),
      whereas OPG was not altered. In contrast, 5T33MM-bearing mice had no changes in
      osteoclast surface or trabecular bone volume and did not develop osteolytic
      lesions. Soluble mRANKL was undetectable in serum from 5T33MM-bearing mice. In
      separate experiments, RPMI-8226 human myeloma cells were transduced with an human
      RANKL/eGFP construct, or eGFP alone. RPMI-8226/hRANKL/eGFP cells, but not RPMI
      8226/eGFP cells, stimulated osteoclastic bone resorption (p<0.05) in vitro. Sub
      cutaneous injection of NOD/SCID mice with RPMI-8226/hRANKL/eGFP or RPMI-8226/eGFP
      cells resulted in tumour development in all mice. RPMI-8226/hRANKL/eGFP-bearing
      mice exhibited increased serum soluble hRANKL (p<0.05) and a three-fold increase
      in osteoclast number (p<0.05) compared to RPMI-8226/eGFP-bearing mice. This was
      associated with reduced trabecular bone volume (27%, p<0.05), decreased
      trabecular number (29%, p<0.05) and increased trabecular thickness (8%, p<0.05).
      Our findings demonstrate that soluble RANKL produced by myeloma cells causes
      generalised bone loss, suggesting that targeting RANKL may prevent osteoporosis
      in patients with myeloma.

PMID- 22952579
TI  - Icaritin, an exogenous phytomolecule, enhances osteogenesis but not angiogenesis-
      an in vitro efficacy study.
AB  - We found that Icaritin, an intestinal metabolite of Epimedium-derived flavonoids
      (EF) enhanced osteoblastic differentiation of mesenchymal stem cells (MSCs) only
      under osteogenic induction conditions. We also demonstrated its effect on
      inhibition of adipogenic differentiation of MSCs. Unlike the findings of others
      on EF compounds, we showed that Icaritin was unable to promote proliferation,
      migration and tube like structure formation by human umbilical vein endothelial
      cells (HUVECs) in vitro. These results suggested that the exogenous phytomolecule
      Icaritin possessed the potential for enhancing bone formation via its
      osteopromotive but not an osteoinductive mechanism. Though some flavonoids were
      shown to regulate the coupling process of angiogenesis and osteogenesis during
      bone repair, our results suggested that Icaritin did not have direct effect on
      enhancing angiogenesis in vitro.

PMID- 22952580
TI  - Early-onset ventilator-associated pneumonia in adults randomized clinical trial:
      comparison of 8 versus 15 days of antibiotic treatment.
AB  - PURPOSE: The optimal treatment duration for ventilator-associated pneumonia is
      based on one study dealing with late-onset of the condition. Shortening the
      length of antibiotic treatment remains a major prevention factor for the
      emergence of multiresistant bacteria. OBJECTIVE: To demonstrate that 2 different
      antibiotic treatment durations (8 versus 15 days) are equivalent in terms of
      clinical cure for early-onset ventilator-associated pneumonia. METHODS:
      Randomized, prospective, open, multicenter trial carried out from 1998 to 2002.
      MEASUREMENTS: The primary endpoint was the clinical cure rate at day 21. The
      mortality rate was evaluated on days 21 and 90. RESULTS: 225 patients were
      included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in
      the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference =
      0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and
      odds ratio were [-8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into
      account the limits of equivalence (10% for difference and 2.25 for odds ratio),
      the objective of demonstrative equivalence between the 2 treatment durations was
      fulfilled. Although the rate of secondary infection was greater in the 8 day than
      the 15 day cohort, the number of days of antibiotic treatment remained lower in
      the 8 day cohort. There was no difference in mortality rate between the 2 groups
      on days 21 and 90. CONCLUSION: Our results suggest that an 8-day course of
      antibiotic therapy is safe for early-onset ventilator-associated pneumonia in
      intubated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01559753.

PMID- 22952581
TI  - Rule-based modeling of chronic disease epidemiology: elderly depression as an
      illustration.
AB  - BACKGROUND: Rule-based Modeling (RBM) is a computer simulation modeling
      methodology already used to model infectious diseases. Extending this technique
      to the assessment of chronic diseases, mixing quantitative and qualitative data
      appear to be a promising alternative to classical methods. Elderly depression
      reveals an important source of comorbidities. Yet, the intertwined relationship
      between late-life events and the social support of the elderly person remains
      difficult to capture. We illustrate the usefulness of RBM in modeling chronic
      diseases using the example of elderly depression in Belgium. METHODS: We defined
      a conceptual framework of interactions between late-life events and social
      support impacting elderly depression. This conceptual framework was underpinned
      by experts' opinions elicited through a questionnaire. Several scenarios were
      implemented successively to better mimic the real population, and to explore a
      treatment effect and a socio-economic distinction. The simulated patterns of
      depression by age were compared with empirical patterns retrieved from the
      Belgian Health Interview Survey. RESULTS: Simulations were run using different
      groupings of experts' opinions on the parameters. The results indicate that the
      conceptual framework can reflect a realistic evolution of the prevalence of
      depression. Indeed, simulations combining the opinions of well-selected experts
      and a treatment effect showed no significant difference with the empirical
      pattern. CONCLUSIONS: Our conceptual framework together with a quantification of
      parameters through elicited expert opinions improves the insights into possible
      dynamics driving elderly depression. While RBM does not require high-level skill
      in mathematics or computer programming, the whole implementation process provides
      a powerful tool to learn about complex chronic diseases, combining advantages of
      both quantitative and qualitative approaches.

PMID- 22952582
TI  - Aberrant CD40-induced NF-kappaB activation in human lupus B lymphocytes.
AB  - Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles
      in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we
      analyzed CD40 expression and CD40/CD154 induced activation of NF-kappaB signaling
      pathway in B cells from SLE patients. B cells from healthy volunteers and
      tonsilar B cells from chronic tonsillitis were used as negative and positive
      controls. Results showed CD40-induced NF-kappaB signaling was constitutively
      activated in B cells from active lupus patients, including decreased CD40 in raft
      portion, increased phosphorylation and degradation of IkappaBalpha,
      phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c
      Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further
      phosphorylation and degradation of IkappaBalpha, as well as phosphorylation of
      P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities
      in B cells from lupus patients mimicked that of tonsil B cells, in that
      IKKalpha/beta were more activated compared to normal B cells. CD40-induced NF
      kappaB activity was blocked by both IkappaB phosphorylation and proteosome
      degradation inhibitors in both lupus and normal B cells. All together, our
      findings revealed that canonical NF-kappaB signaling is constitutively activated
      in active lupus and is mediated by CD154/CD40. CD40 induced NF-kappaB activation
      is different in human lupus B lymphocytes compared with normal B cells.

PMID- 22952583
TI  - The weak complex between RhoGAP protein ARHGAP22 and signal regulatory protein 14
      3-3 has 1:2 stoichiometry and a single peptide binding mode.
AB  - ARHGAP22 is a RhoGAP protein comprising an N-terminal PH domain, a RhoGAP domain
      and a C-terminal coiled-coil domain. It has recently been identified as an Akt
      substrate that binds 14-3-3 proteins in response to treatment with growth factors
      involved in cell migration. We used a range of biophysical techniques to
      investigate the weak interaction between 14-3-3 and a truncated form of ARHGAP22
      lacking the coiled-coil domain. This weak interaction could be stabilized by
      chemical cross-linking which we used to show that: a monomer of ARHGAP22 binds a
      dimer of 14-3-3; the ARHGAP22 PH domain is required for the 14-3-3 interaction;
      the RhoGAP domain is unlikely to participate in the interaction; Ser16 is the
      more important of two predicted 14-3-3 binding sites; and, phosphorylation of
      Ser16 may not be necessary for 14-3-3 interaction under the conditions we used.
      Small angle X-ray scattering and cross-link information were used to generate
      solution structures of the isolated proteins and of the cross-linked ARHGAP22:14
      3-3 complex, showing that no major rearrangement occurs in either protein upon
      binding, and supporting a role for the PH domain and N-terminal peptide of
      ARHGAP22 in the 14-3-3 interaction. Small-angle X-ray scattering measurements of
      mixtures of ARHGAP22 and 14-3-3 were used to establish that the affinity of the
      interaction is ~30 uM.

PMID- 22952584
TI  - Detection of a diverse marine fish fauna using environmental DNA from seawater
      samples.
AB  - Marine ecosystems worldwide are under threat with many fish species and
      populations suffering from human over-exploitation. This is greatly impacting
      global biodiversity, economy and human health. Intriguingly, marine fish are
      largely surveyed using selective and invasive methods, which are mostly limited
      to commercial species, and restricted to particular areas with favourable
      conditions. Furthermore, misidentification of species represents a major problem.
      Here, we investigate the potential of using metabarcoding of environmental DNA
      (eDNA) obtained directly from seawater samples to account for marine fish
      biodiversity. This eDNA approach has recently been used successfully in
      freshwater environments, but never in marine settings. We isolate eDNA from 1/2
      litre seawater samples collected in a temperate marine ecosystem in Denmark.
      Using next-generation DNA sequencing of PCR amplicons, we obtain eDNA from 15
      different fish species, including both important consumption species, as well as
      species rarely or never recorded by conventional monitoring. We also detect eDNA
      from a rare vagrant species in the area; European pilchard (Sardina pilchardus).
      Additionally, we detect four bird species. Records in national databases
      confirmed the occurrence of all detected species. To investigate the efficiency
      of the eDNA approach, we compared its performance with 9 methods conventionally
      used in marine fish surveys. Promisingly, eDNA covered the fish diversity better
      than or equal to any of the applied conventional methods. Our study demonstrates
      that even small samples of seawater contain eDNA from a wide range of local fish
      species. Finally, in order to examine the potential dispersal of eDNA in oceans,
      we performed an experiment addressing eDNA degradation in seawater, which shows
      that even small (100-bp) eDNA fragments degrades beyond detectability within
      days. Although further studies are needed to validate the eDNA approach in
      varying environmental conditions, our findings provide a strong proof-of-concept
      with great perspectives for future monitoring of marine biodiversity and
      resources.

PMID- 22952585
TI  - An image-based drug susceptibility assay targeting the placental sequestration of
      Plasmodium falciparum-infected erythrocytes.
AB  - Placental malaria is a significant cause of all malaria-related deaths globally
      for which no drugs have been developed to specifically disrupt its pathogenesis.
      To facilitate the discovery of antimalarial drugs targeting the cytoadherence
      process of Plasmodium-infected erythrocytes in the placenta microvasculature, we
      have developed an automated image-based assay for high-throughput screening for
      potent cytoadherence inhibitors in vitro. Parasitized erythrocytes were drug
      treated for 24 h and then allowed to adhere on a monolayer of placental BeWo
      cells prior to red blood cell staining with glycophorin A antibodies. Upon image
      acquisition, drug effects were quantified as the proportion of treated
      parasitized erythrocytes to BeWo cells compared to the binding of untreated
      iRBCs. We confirmed the reliability of this new assay by comparing the binding
      ratios of CSA- and CD36-panned parasites on the placental BeWo cells, and by
      quantifying the effects of chondroitin sulfate A, brefeldin A, and artemisinin on
      the binding. By simultaneously examining the drug effects on parasite viability,
      we could discriminate between cytoadherence-specific inhibitors and other
      schizonticidal compounds. Taken together, our data establish that the developed
      assay is highly suitable for drug studies targeting placental malaria, and will
      facilitate the discovery and rapid development of new therapies against malaria.

PMID- 22952586
TI  - Biopsychosocial health care needs at the emergency room: challenge of complexity.
AB  - BACKGROUND: In an emergency room of internal medicine, triage and treatment of
      patients deserve first priority. However, biopsychosocial case complexity may
      also affect patient health outcome but has not yet been explored in this setting.
      Therefore, the aims of the study are (1) to estimate prevalence rates of complex
      patients in the emergency room (ER), (2) to describe biopsychosocial complexity
      in this population and (3) to evaluate possible correlations between patient
      profiles regarding case complexity and further clinical treatment. METHODS:
      During a study period of one week, all patients of an emergency room of internal
      medicine who were triaged to Manchester levels three to five were invited to
      participate in the study. Biopsychosocial case complexity was assessed by the
      INTERMED method. Psychosocial interventions were evaluated based on all
      documented interventions and recommendations given at the emergency room and
      during inpatient treatment. RESULTS: Study participants consisted of 167 patients
      with a subgroup of 19% (n = 32) receiving subsequent inpatient-treatment at the
      department. High biopsychosocial case complexity was found in 12% (n = 20) of the
      total sample (INTERMED score >20). This finding was paralleled by a cluster
      analysis suggesting three clusters with one highly complex patient group of 14%.
      These highly complex patients differed significantly from the other clusters as
      they had visited the emergency room more often within the last year and lived
      alone more frequently. In addition, admission rates were highest in this group.
      During ER treatment and subsequent inpatient treatment, 21% of highly complex
      patients received interventions addressing psychosocial factors as compared to 6%
      and 7%, respectively, in the other clusters. CONCLUSIONS: A standardized
      screening of biopsychosocial case complexity among 'frequent utilizers' of the ER
      would be helpful to detect specific multidisciplinary health care needs among
      this particularly burdened patient group.

PMID- 22952587
TI  - Investigating the potential use of environmental DNA (eDNA) for genetic
      monitoring of marine mammals.
AB  - The exploitation of non-invasive samples has been widely used in genetic
      monitoring of terrestrial species. In aquatic ecosystems, non-invasive samples
      such as feces, shed hair or skin, are less accessible. However, the use of
      environmental DNA (eDNA) has recently been shown to be an effective tool for
      genetic monitoring of species presence in freshwater ecosystems. Detecting
      species in the marine environment using eDNA potentially offers a greater
      challenge due to the greater dilution, amount of mixing and salinity compared
      with most freshwater ecosystems. To determine the potential use of eDNA for
      genetic monitoring we used specific primers that amplify short mitochondrial DNA
      sequences to detect the presence of a marine mammal, the harbor porpoise,
      Phocoena phocoena, in a controlled environment and in natural marine locations.
      The reliability of the genetic detections was investigated by comparing with
      detections of harbor porpoise echolocation clicks by static acoustic monitoring
      devices. While we were able to consistently genetically detect the target species
      under controlled conditions, the results from natural locations were less
      consistent and detection by eDNA was less successful than acoustic detections.
      However, at one site we detected long-finned pilot whale, Globicephala melas, a
      species rarely sighted in the Baltic. Therefore, with optimization aimed towards
      processing larger volumes of seawater this method has the potential to compliment
      current visual and acoustic methods of species detection of marine mammals.

PMID- 22952588
TI  - Innate non-specific cell substratum adhesion.
AB  - Adhesion of motile cells to solid surfaces is necessary to transmit forces
      required for propulsion. Unlike mammalian cells, Dictyostelium cells do not make
      integrin mediated focal adhesions. Nevertheless, they can move rapidly on both
      hydrophobic and hydrophilic surfaces. We have found that adhesion to such
      surfaces can be inhibited by addition of sugars or amino acids to the buffer.
      Treating whole cells with alphalpha-mannosidase to cleave surface
      oligosaccharides also reduces adhesion. The results indicate that adhesion of
      these cells is mediated by van der Waals attraction of their surface
      glycoproteins to the underlying substratum. Since glycoproteins are prevalent
      components of the surface of most cells, innate adhesion may be a common cellular
      property that has been overlooked.

PMID- 22952589
TI  - Inference of biological pathway from gene expression profiles by time delay
      boolean networks.
AB  - One great challenge of genomic research is to efficiently and accurately identify
      complex gene regulatory networks. The development of high-throughput technologies
      provides numerous experimental data such as DNA sequences, protein sequence, and
      RNA expression profiles makes it possible to study interactions and regulations
      among genes or other substance in an organism. However, it is crucial to make
      inference of genetic regulatory networks from gene expression profiles and
      protein interaction data for systems biology. This study will develop a new
      approach to reconstruct time delay boolean networks as a tool for exploring
      biological pathways. In the inference strategy, we will compare all pairs of
      input genes in those basic relationships by their corresponding p-scores for
      every output gene. Then, we will combine those consistent relationships to reveal
      the most probable relationship and reconstruct the genetic network. Specifically,
      we will prove that O(log n) state transition pairs are sufficient and necessary
      to reconstruct the time delay boolean network of n nodes with high accuracy if
      the number of input genes to each gene is bounded. We also have implemented this
      method on simulated and empirical yeast gene expression data sets. The test
      results show that this proposed method is extensible for realistic networks.

PMID- 22952591
TI  - Prevalence, genotype distribution and persistence of human papillomavirus in oral
      mucosa of women: a six-year follow-up study.
AB  - BACKGROUND: Human papillomavirus (HPV) infections have been linked to a subset of
      oral and oropharyngeal cancers. However, little is known on the natural history
      of oral HPV infections. We designed the prospective Finnish HPV Family Study to
      assess the dynamics of HPV infections in parents and their infants. This study
      reports HPV genotype distribution and virus persistence in oral mucosa of the
      mothers. MATERIALS AND METHODS: Totally, 324 pregnant women were enrolled at the
      3(rd) trimester of pregnancy and followed-up for 6 years. Oral scrapings taken
      with a brush were collected and HPV-genotyping was performed with nested PCR and
      Multimetrix(r) test (Progen, Heidelberg, Germany). The predictors of persistent
      oral HPV species 7/9 infections were analyzed using generalized estimating
      equation models. RESULTS: The point prevalence of oral HPV varied from 15% to 24%
      during the 6-year follow-up. Altogether, 18 HPV genotypes were identified either
      as single or multiple-type oral infections. HPV16 was the most prevalent type at
      9.7%-18.4%, followed by HPV18, HPV6, and multiple infections. Altogether, 74
      women had persistent oral HPV infection determined as at least two consecutive
      samples positive with the same HPV genotype. HPV16 and HPV6 were the two most
      frequent types to persist (76% and 9%) for a mean of 18.6 and 20.2 months,
      respectively, followed by multiple infections (8%) for 18.3 months. An increased
      risk for persistent oral HPV infection with species 7/9 was associated with being
      seropositive for low-risk (LR)-HPV-types at baseline, whereas the use of oral
      contraceptives and a second pregnancy during follow-up were protective. Clinical
      oral lesions were detected in 17% of these women, one-third of whom had
      persistent oral HPV-infections. CONCLUSION: HPV16 and HPV6 were the most common
      genotypes in oral HPV-infections and were also most likely to persist. Use of
      oral contraceptives and a second pregnancy protected against oral HPV
      persistence.

PMID- 22952590
TI  - The spectrum of central nervous system infections in an adult referral hospital
      in Hanoi, Vietnam.
AB  - OBJECTIVES: To determine prospectively the causative pathogens of central nervous
      system (CNS) infections in patients admitted to a tertiary referral hospital in
      Hanoi, Vietnam. METHODS: From May 2007 to December 2008, cerebrospinal fluid
      (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent
      routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and
      polymerase chain reaction targeting Neisseria meningitidis, Streptococcus
      pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV),
      Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures
      and clinically indicated radiology were also performed. Patients were classified
      as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal
      (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM),
      neurocysticercosis and others. RESULTS: 352 (male: 66%) patients were recruited:
      median age 34 years (range 13-85). 95/352 (27.3%) diagnoses were laboratory
      confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19),
      CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis
      predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1),
      S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses
      were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of
      262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital
      referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM
      (15.2%), AEM (10%), and BM (2.8%). CONCLUSIONS: Most infections lacked
      microbiological confirmation. S. suis was the most common cause of BM in this
      setting. Improved diagnostics are needed for meningoencephalitic syndromes to
      inform treatment and prevention strategies.

PMID- 22952592
TI  - 3D multi-isotope imaging mass spectrometry reveals penetration of 18O-trehalose
      in mouse sperm nucleus.
AB  - The prevalence of genetically engineered mice in medical research has led to ever
      increasing storage costs. Trehalose has a significant beneficial effect in
      preserving the developmental potential of mouse sperm following partial
      desiccation and storage at temperatures above freezing. Using multi-isotope
      imaging mass spectrometry, we are able to image and measure trehalose in
      individual spermatozoa. We provide the first evidence that trehalose penetrates
      the nucleus of a mammalian cell, permitting tolerance to desiccation. These
      results have broad implications for long-term storage of mammalian cells.

PMID- 22952593
TI  - Gene expression and DNA-methylation of bovine pretransfer endometrium depending
      on its receptivity after in vitro-produced embryo transfer.
AB  - Embryonic implantation to establish a pregnancy is a complex process that
      requires appropriate communication between the embryo and the maternal
      endometrium. Inadequate uterine receptivity may contribute to the majority of
      implantation failures. To provide a comprehensive inventory of genes and
      functional networks that represent the maternal input of the embryo-maternal
      cross-talk, a longitudinal, holistic study of the endometrial transcriptome in
      relation to the days of estrous and to the receptivity of the endometrium was
      performed in bovine. At day 3 of estrous, genes related to cell communication and
      mitochondrial energy metabolism were differentially expressed among high- and low
      receptive endometria (HR, LR); at day 7, transcripts functioning in immune and
      inflammatory pathways, oxidative stress, and angiogenesis had different
      abundances. Additionally, temporal transcriptional changes between days 3 and 7
      differed considerably among HR and LR. Further, several transcription factors
      were predicted as relevant for receptivity because they were either
      differentially expressed among HR and LR animals or are known to be associated
      with genes we detected to have differential expression. Finally, global DNA
      methylation varied according to the interaction of receptivity group and day of
      estrous, and a divergent trend, which correlated with abundance of DNMT1
      transcript, was observed in LR and HR along the estrous cycle days. The study
      revealed that, even in early estrous, transcripts related to cell communication
      and response to exogenous stimuli, vascularization, and energy supply show
      divergent expression and longitudinal temporal regulation in HR and LR. Key
      components of these molecular pathways are known to be dependent on ovarian
      hormones that promote uterine receptivity.

PMID- 22952594
TI  - Aspergillus bertholletius sp. nov. from Brazil nuts.
AB  - During a study on the mycobiota of brazil nuts (Bertholletia excelsa) in Brazil,
      a new Aspergillus species, A. bertholletius, was found, and is described here. A
      polyphasic approach was applied using morphological characters, extrolite data as
      well as partial beta-tubulin, calmodulin and ITS sequences to characterize this
      taxon. A. bertholletius is represented by nineteen isolates from samples of
      brazil nuts at various stages of production and soil close to Bertholletia
      excelsa trees. The following extrolites were produced by this species: aflavinin,
      cyclopiazonic acid, kojic acid, tenuazonic acid and ustilaginoidin C.
      Phylogenetic analysis using partial beta-tubulin and camodulin gene sequences
      showed that A. bertholletius represents a new phylogenetic clade in Aspergillus
      section Flavi. The type strain of A. bertholletius is CCT 7615 ( = ITAL 270/06 =
      IBT 29228).

PMID- 22952595
TI  - Estimating the numbers of malaria infections in blood samples using high
      resolution genotyping data.
AB  - People living in endemic areas often habour several malaria infections at once.
      High-resolution genotyping can distinguish between infections by detecting the
      presence of different alleles at a polymorphic locus. However the number of
      infections may not be accurately counted since parasites from multiple infections
      may carry the same allele. We use simulation to determine the circumstances under
      which the number of observed genotypes are likely to be substantially less than
      the number of infections present and investigate the performance of two methods
      for estimating the numbers of infections from high-resolution genotyping data.
      The simulations suggest that the problem is not substantial in most datasets: the
      disparity between the mean numbers of infections and of observed genotypes was
      small when there was 20 or more alleles, 20 or more blood samples, a mean number
      of infections of 6 or less and where the frequency of the most common allele was
      no greater than 20%. The issue of multiple infections carrying the same allele is
      unlikely to be a major component of the errors in PCR-based genotyping.
      Simulations also showed that, with heterogeneity in allele frequencies, the
      observed frequencies are not a good approximation of the true allele frequencies.
      The first method that we proposed to estimate the numbers of infections assumes
      that they are a good approximation and hence did poorly in the presence of
      heterogeneity. In contrast, the second method by Li et al estimates both the
      numbers of infections and the true allele frequencies simultaneously and produced
      accurate estimates of the mean number of infections.

PMID- 22952596
TI  - Dominant incidence of multidrug and extensively drug-resistant specific
      Mycobacterium tuberculosis clones in Osaka Prefecture, Japan.
AB  - Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR
      Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health
      problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and
      neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were
      identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR
      Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on
      mycobacterial interspersed repetitive units-various number of tandem repeats
      (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM
      V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis
      revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from
      OM-V04 were clonal. Importantly such genotypes were not observed for drug
      sensitive isolates. These suggest that few but transmissible clones can transmit
      after acquiring multidrug resistance and colonize even in a country with a
      developed, well-organized healthcare system.

PMID- 22952597
TI  - Priming of social distance? Failure to replicate effects on social and food
      judgments.
AB  - Williams and Bargh (2008) reported an experiment in which participants were
      simply asked to plot a single pair of points on a piece of graph paper, with the
      coordinates provided by the experimenter specifying a pair of points that lay at
      one of three different distances (close, intermediate, or far, relative to the
      range available on the graph paper). The participants who had graphed a more
      distant pair reported themselves as being significantly less close to members of
      their own family than did those who had plotted a more closely-situated pair. In
      another experiment, people's estimates of the caloric content of different foods
      were reportedly altered by the same type of spatial distance priming. Direct
      replications of both results were attempted, with precautions to ensure that the
      experimenter did not know what condition the participant was assigned to. The
      results showed no hint of the priming effects reported by Williams and Bargh
      (2008).

PMID- 22952598
TI  - Fish oil supplementation alters the plasma lipidomic profile and increases long
      chain PUFAs of phospholipids and triglycerides in healthy subjects.
AB  - BACKGROUND: While beneficial health effects of fish and fish oil consumption are
      well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma
      lipid classes is not completely understood. The aim of this study was to
      investigate the effect of fish oil supplementation on the plasma lipidomic
      profile in healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: In a double-blinded
      randomized controlled parallel-group study, healthy subjects received capsules
      containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of
      high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three
      weeks of intervention, the subjects completed a fully controlled diet period. BMI
      and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged
      during the intervention period. Lipidomic analyses were performed using Ultra
      Performance Liquid Chromatography (UPLC) coupled to electrospray ionization
      quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were
      detected and 260 identified. Both t-tests and Multi-Block Partial Least Square
      Regression (MBPLSR) analysis were performed for analysing differences between the
      intervention groups. The intervention groups were well separated by the lipidomic
      data after three weeks of intervention. Several lipid classes such as
      phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine,
      sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides
      contributed strongly to this separation. Twenty-three lipids were significantly
      decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO
      group, whereas fifty-one were increased including selected phospholipids and
      triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of
      intervention the two intervention groups showed similar grouping.
      CONCLUSIONS/SIGNIFICANCE: In healthy subjects, fish oil supplementation alters
      lipid metabolism and increases the proportion of phospholipids and triglycerides
      containing long-chain polyunsaturated fatty acids. Whether the beneficial effects
      of fish oil supplementation may be explained by a remodeling of the plasma lipids
      into phospholipids and triglycerides of long-chain polyunsaturated fatty acids
      needs to be further investigated. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01034423.

PMID- 22952599
TI  - Decreased premotor cortex volume in victims of urban violence with posttraumatic
      stress disorder.
AB  - BACKGROUND: Studies addressing posttraumatic stress disorder (PTSD) have
      demonstrated that PTSD patients exhibit structural abnormalities in brain regions
      that relate to stress regulation and fear responses, such as the hippocampus,
      amygdala, anterior cingulate cortex, and ventromedial prefrontal cortex. Premotor
      cortical areas are involved in preparing to respond to a threatening situation
      and in representing the peripersonal space. Urban violence is an important and
      pervasive cause of human suffering, especially in large urban centers in the
      developing world. Violent events, such as armed robbery, are very frequent in
      certain cities, and these episodes increase the risk of PTSD. Assaultive trauma
      is characterized by forceful invasion of the peripersonal space; therefore, could
      this traumatic event be associated with structural alteration of premotor areas
      in PTSD? METHODOLOGY/PRINCIPAL FINDINGS: Structural magnetic resonance imaging
      scans were acquired from a sample of individuals that had been exposed to urban
      violence. This sample consisted of 16 PTSD patients and 16 age- and gender
      matched controls. Psychometric questionnaires differentiated PTSD patients from
      trauma-exposed controls with regard to PTSD symptoms, affective, and resilience
      predispositions. Voxel-based morphometric analysis revealed that, compared with
      controls, the PTSD patients presented significant reductions in gray matter
      volume in the ventral premotor cortex and in the pregenual anterior cingulate
      cortex. CONCLUSIONS: Volume reduction in the premotor cortex that is observed in
      victims of urban violence with PTSD may be associated with a disruption in the
      dynamical modulation of the safe space around the body. The finding that PTSD
      patients presented a smaller volume of pregenual anterior cingulate cortex is
      consistent with the results of other PTSD neuroimaging studies that investigated
      different types of traumatic events.

PMID- 22952600
TI  - Relationship between microbial translocation and endothelial function in HIV
      infected patients.
AB  - BACKGROUND: Circulating levels of microbial products are increased in HIV
      infection, and provoke endothelial dysfunction in other disease settings.
      METHODOLOGY/PRINCIPAL FINDINGS: We examined data from a cross-sectional single
      site study at Indiana University (Indiana, N = 85) and a 24- week multicenter
      prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N =
      75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound.
      Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured
      from stored specimens and correlated with FMD values using Pearson correlations.
      The Indiana subjects were 63% male with a mean age of 39 years and a median CD4
      count of 406 cells/mm(3) (388 not on ART, 464 on ART). The 5152s subjects were
      92% were male with a mean age of 35 years and a median CD4 count of 251
      cells/mm(3) at entry which increased to 396 cells/mm(3) on ART. When analyzing
      the two cohorts individually or in combination neither sCD14 nor LPS correlated
      significantly with FMD. In a pre-specified subgroup analysis of the Indiana
      subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely
      correlated with FMD (r = -0.33, p = 0.02), but not sCD14 (r = -0.01, p = 0.9).
      Multivariate analysis confirmed LPS as an independent predictor of FMD in this
      subgroup (p = 0.02). CONCLUSIONS/SIGNIFICANCE: In HIV-infected individuals on
      prolonged ART, higher LPS levels are associated with worse endothelial function
      but not in untreated subjects or at 24 weeks after ART initiation. Persistent
      microbial translocation may contribute to arterial dysfunction and the increased
      cardiovascular disease risk observed in individuals on long-term ART.

PMID- 22952601
TI  - Dietary factors associated with dental erosion: a meta-analysis.
AB  - BACKGROUND: Some diet factors are risk factors for dental erosion. METHODS: We
      performed computer searches of PubMed, Cochrane Library, EBSCO, CALIS, et al., to
      search for studies investigating risk factors for dental erosion. For risk
      factors investigated in a comparative way, we computed pooled odds ratios (ORs)
      using the Mantel and Haenszel method. RESULTS: A total of 9 studies met the
      inclusion criteria, and 6 risk factors were considered, including soft drinks,
      sports drinks, juice, vitamin C, milk, and yoghourt. The following associations
      were found for soft drinks (OR = 2.41, 95%CI = 2.03-2.85) and vitamin C (OR =
      1.16, 95%CI = 1.10-1.22). While juice (OR = 0.90, 95%CI = 0.25-3.24), sports
      drinks (OR = 1.58, 95%CI = 0.88-2.85), milk (OR = 0.67, 95%CI = 0.11-4.01), and
      yoghourt products (OR = 1.05, 95%CI = 0.28-3.96) were not associated with dental
      erosion. CONCLUSIONS: This meta-analysis provides comprehensive evidence-based
      assessment of diet-related factors for dental erosion. Preventive strategies
      should be taken to reduce dental erosion.

PMID- 22952602
TI  - Preconditioning triggered by carbon monoxide (CO) provides neuronal protection
      following perinatal hypoxia-ischemia.
AB  - Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and
      cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to
      excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play
      a major role. Increased resistance against major damage can be achieved by
      preconditioning triggered by subtle insults. CO, a toxic molecule that is also
      generated endogenously, may have a role in preconditioning as low doses can
      protect against inflammation and apoptosis. In this study, the role of CO-induced
      preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h
      of CO treatment on neuronal death (plasmatic membrane permeabilization and
      chromatin condensation) and bcl-2 expression was studied in cerebellar granule
      cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in
      the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery
      ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were
      counted with a stereological approach and cleaved caspase 3-positive profiles in
      the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal
      extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and
      increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented
      hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c
      released from mitochondria and reduced activation of caspase-3. Still, Bcl-2
      protein levels were higher in hippocampus of CO pre-treated rat pups. Our results
      show that CO preconditioning elicits a molecular cascade that limits neuronal
      apoptosis. This could represent an innovative therapeutic strategy for high-risk
      cerebral hypoxia-ischemia patients, in particular neonates.

PMID- 22952604
TI  - The role of master regulators in the metabolic/transcriptional coupling in breast
      carcinomas.
AB  - Metabolic transformations have been reported as involved in neoplasms survival.
      This suggests a role of metabolic pathways as potential cancer pharmacological
      targets. Modulating tumor's energy production pathways may become a substantial
      research area for cancer treatment. The significant role of metabolic
      deregulation as inducing transcriptional instabilities and consequently whole
      system failure, is thus of foremost importance. By using a data integration
      approach that combines experimental evidence for high-throughput genome wide gene
      expression, a non-equilibrium thermodynamics analysis, nonlinear correlation
      networks as well as database mining, we were able to outline the role that
      transcription factors MEF2C and MNDA may have as main master regulators in
      primary breast cancer phenomenology, as well as the possible interrelationship
      between malignancy and metabolic dysfunction. The present findings are supported
      by the analysis of 1191 whole genome gene expression experiments, as well as
      probabilistic inference of gene regulatory networks, and non-equilibrium
      thermodynamics of such data. Other evidence sources include pathway enrichment
      and gene set enrichment analyses, as well as motif comparison with a
      comprehensive gene regulatory network (of homologue genes) in Arabidopsis
      thaliana. Our key finding is that the non-equilibrium free energies provide a
      realistic description of transcription factor activation that when supplemented
      with gene regulatory networks made us able to find deregulated pathways. These
      analyses also suggest a novel potential role of transcription factor energetics
      at the onset of primary tumor development. Results are important in the molecular
      systems biology of cancer field, since deregulation and coupling mechanisms
      between metabolic activity and transcriptional regulation can be better
      understood by taking into account the way that master regulators respond to
      physicochemical constraints imposed by different phenotypic conditions.

PMID- 22952603
TI  - Genome-wide association study of d-amphetamine response in healthy volunteers
      identifies putative associations, including cadherin 13 (CDH13).
AB  - Both the subjective response to d-amphetamine and the risk for amphetamine
      addiction are known to be heritable traits. Because subjective responses to drugs
      may predict drug addiction, identifying alleles that influence acute response may
      also provide insight into the genetic risk factors for drug abuse. We performed a
      Genome Wide Association Study (GWAS) for the subjective responses to amphetamine
      in 381 non-drug abusing healthy volunteers. Responses to amphetamine were
      measured using a double-blind, placebo-controlled, within-subjects design. We
      used sparse factor analysis to reduce the dimensionality of the data to ten
      factors. We identified several putative associations; the strongest was between a
      positive subjective drug-response factor and a SNP (rs3784943) in the 8(th)
      intron of cadherin 13 (CDH13; P = 4.58*10(-8)), a gene previously associated with
      a number of psychiatric traits including methamphetamine dependence.
      Additionally, we observed a putative association between a factor representing
      the degree of positive affect at baseline and a SNP (rs472402) in the 1(st)
      intron of steroid-5-alpha-reductase-alpha-polypeptide-1 (SRD5A1; P = 2.53*10(
      7)), a gene whose protein product catalyzes the rate-limiting step in synthesis
      of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has
      been previously associated with the expression of SRD5A1 and differences in
      SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the
      genetic basis of subjective responses to stimulant drugs using a GWAS approach in
      a modestly sized sample. Our approach provides a case study for analysis of high
      dimensional intermediate pharmacogenomic phenotypes, which may be more tractable
      than clinical diagnoses.

PMID- 22952605
TI  - Simultaneous measurements of auto-immune and infectious disease specific
      antibodies using a high throughput multiplexing tool.
AB  - Considering importance of ganglioside antibodies as biomarkers in various immune
      mediated neuropathies and neurological disorders, we developed a high throughput
      multiplexing tool for the assessment of gangliosides-specific antibodies based on
      Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside
      high throughput multiplexing tool is robust, highly specific and demonstrating
      ~100-fold higher concentration sensitivity for IgG detection than ELISA. In
      addition to the ganglioside-coated array, the high throughput multiplexing tool
      contains beads coated with influenza hemagglutinins derived from H1N1
      A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an
      added advantage of simultaneous detection of ganglioside- and influenza-specific
      antibodies, a capacity important for the assay of both infectious antigen
      specific and autoimmune antibodies following vaccination or disease. Taken
      together, these results support the potential adoption of the ganglioside high
      throughput multiplexing tool for measuring ganglioside antibodies in various
      neuropathic and neurological disorders.

PMID- 22952606
TI  - CSF N-glycan profiles to investigate biomarkers in brain developmental disorders:
      application to leukodystrophies related to eIF2B mutations.
AB  - BACKGROUND: Primary or secondary abnormalities of glycosylation have been
      reported in various brain diseases. Decreased asialotransferrin to
      sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of
      leukodystrophies related to mutations of genes encoding translation initiation
      factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age
      matched normal individuals in order to further characterize the glycosylation
      defect for possible use as a biomarker. METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N
      glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in
      control CSF that tri-antennary/bisecting and high mannose structures were highly
      represented in samples obtained between 1 to 5 years of age, whereas fucosylated,
      sialylated structures were predominant at later age. In CSF, but not in plasma,
      of eIF2B-mutated patient samples, we found increased relative intensity of bi
      antennary structures and decreased tri-antennary/bisecting structures in N-glycan
      profiles. Four of these structures appeared to be biomarker candidates of
      glycomic profiles of eIF2B-related disorders. CONCLUSION: Our results suggest a
      dynamic development of normal CSF N-glycan profiles from high mannose type
      structures to complex sialylated structures that could be correlated with
      postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative
      changes associated with eIF2B related disorders. This approach could be applied
      to other neurological disorders involving developmental
      gliogenesis/synaptogenesis abnormalities.

PMID- 22952607
TI  - Comprehensive approach to improving maternal health and achieving MDG 5: report
      from the mountains of Lesotho.
AB  - BACKGROUND: Although it is now widely recognized that reductions in maternal
      mortality and improvements in women's health cannot be achieved through simple,
      vertical strategies, few programs have provided successful models for how to
      integrate services into a comprehensive program for maternal health. We report
      our experience in rural Lesotho, where Partners In Health (PIH) in partnership
      with the Ministry of Health and Social Welfare implemented a program that
      provides comprehensive care of pregnant women from the community to the clinic
      level. METHODS: Between May and July 2009, PIH trained 100 women, many of whom
      were former traditional birth attendants, to serve as clinic-affiliated maternal
      health workers. They received performance-based incentives for accompanying
      pregnant women during antenatal care (ANC) visits and facility-based delivery. A
      nurse-midwife provided ANC and delivery care and supervised the maternal health
      workers. To overcome geographic barriers to delivering at the clinic, women who
      lived far from the clinic stayed at a maternal lying-in house prior to their
      expected delivery dates. We analyzed data routinely collected from delivery and
      ANC registers to compare service utilization before and after implementation of
      the program. RESULTS: After the establishment of the program, the average number
      first ANC visits increased from 20 to 31 per month. The clinic recorded 178
      deliveries in the first year of the program and 216 in the second year, compared
      to 46 in the year preceding the program. During the first two years of the
      program, 49 women with complications were successfully transported to the
      district hospital, and no maternal deaths occurred among the women served by the
      program. CONCLUSIONS: Our results demonstrate that it is possible to achieve
      dramatic improvements in the utilization of maternal health services and facility
      based delivery by strengthening human resource capacity, implementing active
      follow-up in the community, and de-incentivizing home births.

PMID- 22952608
TI  - Effective visual working memory capacity: an emergent effect from the neural
      dynamics in an attractor network.
AB  - The study of working memory capacity is of outmost importance in cognitive
      psychology as working memory is at the basis of general cognitive function.
      Although the working memory capacity limit has been thoroughly studied, its
      origin still remains a matter of strong debate. Only recently has the role of
      visual saliency in modulating working memory storage capacity been assessed
      experimentally and proved to provide valuable insights into working memory
      function. In the computational arena, attractor networks have successfully
      accounted for psychophysical and neurophysiological data in numerous working
      memory tasks given their ability to produce a sustained elevated firing rate
      during a delay period. Here we investigate the mechanisms underlying working
      memory capacity by means of a biophysically-realistic attractor network with
      spiking neurons while accounting for two recent experimental observations: 1) the
      presence of a visually salient item reduces the number of items that can be held
      in working memory, and 2) visually salient items are commonly kept in memory at
      the cost of not keeping as many non-salient items. Our model suggests that
      working memory capacity is determined by two fundamental processes: encoding of
      visual items into working memory and maintenance of the encoded items upon their
      removal from the visual display. While maintenance critically depends on the
      constraints that lateral inhibition imposes to the mnemonic activity, encoding is
      limited by the ability of the stimulated neural assemblies to reach a
      sufficiently high level of excitation, a process governed by the dynamics of
      competition and cooperation among neuronal pools. Encoding is therefore
      contingent upon the visual working memory task and has led us to introduce the
      concept of effective working memory capacity (eWMC) in contrast to the maximal
      upper capacity limit only reached under ideal conditions.

PMID- 22952609
TI  - Acoustic radiation force impulse imaging for differentiation of thyroid nodules.
AB  - BACKGROUND: Acoustic Radiation Force Impulse (ARFI)-Imaging is an ultrasound
      based elastography method enabling quantitative measurement of tissue stiffness.
      The aim of the present study was to evaluate sensitivity and specificity of ARFI
      imaging for differentiation of thyroid nodules and to compare it to the well
      evaluated qualitative real-time elastography (RTE). METHODS: ARFI-imaging
      involves the mechanical excitation of tissue using acoustic pulses to generate
      localized displacements resulting in shear-wave propagation which is tracked
      using correlation-based methods and recorded in m/s. Inclusion criteria were:
      nodules >=5 mm, and cytological/histological assessment. All patients received
      conventional ultrasound, real-time elastography (RTE) and ARFI-imaging. RESULTS:
      One-hundred-fifty-eight nodules in 138 patients were available for analysis. One
      hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one
      nodules were malignant. The median velocity of ARFI-imaging in the healthy
      thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s,
      1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median
      velocity was found between healthy thyroid tissue and benign thyroid nodules, a
      significant difference was found between malignant thyroid nodules on the one
      hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p =
      0.0039) on the other hand. No significant difference of diagnostic accuracy for
      the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging
      (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve
      diagnostic accuracy. CONCLUSIONS: ARFI can be used as an additional tool in the
      diagnostic work up of thyroid nodules with high negative predictive value and
      comparable results to RTE.

PMID- 22952610
TI  - Increasing coverage of transcription factor position weight matrices through
      domain-level homology.
AB  - Transcription factor-DNA interactions, central to cellular regulation and
      control, are commonly described by position weight matrices (PWMs). These
      matrices are frequently used to predict transcription factor binding sites in
      regulatory regions of DNA to complement and guide further experimental
      investigation. The DNA sequence preferences of transcription factors, encoded in
      PWMs, are dictated primarily by select residues within the DNA binding domain(s)
      that interact directly with DNA. Therefore, the DNA binding properties of
      homologous transcription factors with identical DNA binding domains may be
      characterized by PWMs derived from different species. Accordingly, we have
      implemented a fully automated domain-level homology searching method for
      identical DNA binding sequences.By applying the domain-level homology search to
      transcription factors with existing PWMs in the JASPAR and TRANSFAC databases, we
      were able to significantly increase coverage in terms of the total number of PWMs
      associated with a given species, assign PWMs to transcription factors that did
      not previously have any associations, and increase the number of represented
      species with PWMs over an order of magnitude. Additionally, using protein binding
      microarray (PBM) data, we have validated the domain-level method by demonstrating
      that transcription factor pairs with matching DNA binding domains exhibit
      comparable DNA binding specificity predictions to transcription factor pairs with
      completely identical sequences.The increased coverage achieved herein
      demonstrates the potential for more thorough species-associated investigation of
      protein-DNA interactions using existing resources. The PWM scanning results
      highlight the challenging nature of transcription factors that contain multiple
      DNA binding domains, as well as the impact of motif discovery on the ability to
      predict DNA binding properties. The method is additionally suitable for
      identifying domain-level homology mappings to enable utilization of additional
      information sources in the study of transcription factors. The domain-level
      homology search method, resulting PWM mappings, web-based user interface, and web
      API are publicly available at
      http://dodoma.systemsbiology.netdodoma.systemsbiology.net.

PMID- 22952611
TI  - Elucidating the sources of beta-catenin dynamics in human neural progenitor
      cells.
AB  - Human neural progenitor cells (hNPCs) form a new prospect for replacement
      therapies in the context of neurodegenerative diseases. The Wnt/beta-catenin
      signaling pathway is known to be involved in the differentiation process of
      hNPCs. RVM cells form a common cell model of hNPCs for in vitro investigation.
      Previous observations in RVM cells raise the question of whether observed
      kinetics of the Wnt/beta-catenin pathway in later differentiation phases are
      subject to self-induced signaling. However, a concern when investigating RVM
      cells is that experimental results are possibly biased by the asynchrony of cells
      w.r.t. the cell cycle. In this paper, we present, based on experimental data, a
      computational modeling study on the Wnt/beta-catenin signaling pathway in RVM
      cell populations asynchronously distributed w.r.t. to their cell cycle phases.
      Therefore, we derive a stochastic model of the pathway in single cells from the
      reference model in literature and extend it by means of cell populations and cell
      cycle asynchrony. Based on this, we show that the impact of the cell cycle
      asynchrony on wet-lab results that average over cell populations is negligible.
      We then further extend our model and the thus-obtained simulation results provide
      additional evidence that self-induced Wnt signaling occurs in RVM cells. We
      further report on significant stochastic effects that directly result from model
      parameters provided in literature and contradict experimental observations.

PMID- 22952613
TI  - Allografts of the acellular sciatic nerve and brain-derived neurotrophic factor
      repair spinal cord injury in adult rats.
AB  - OBJECTIVE: We aimed to investigate whether an innovative growth factor-laden
      scaffold composed of acellular sciatic nerve (ASN) and brain-derived neurotrophic
      factor (BDNF) could promote axonal regeneration and functional recovery after
      spinal cord injury (SCI). METHODS: Following complete transection at the thoracic
      level (T9), we immediately transplanted the grafts between the stumps of the
      severed spinal cords. We evaluated the functional recovery of the hindlimbs of
      the operated rats using the BBB locomotor rating scale system every week. Eight
      weeks after surgery, axonal regeneration was examined using the fluorogold (FG)
      retrograde tracing method. Electrophysiological analysis was carried out to
      evaluate the improvement in the neuronal circuits. Immunohistochemistry was
      employed to identify local injuries and recovery. RESULTS: The results of the
      Basso-Beattie-Bresnahan (BBB) scale indicated that there was no significant
      difference between the individual groups. The FG retrograde tracing and
      electrophysiological analyses indicated that the transplantation of ASN-BDNF
      provided a permissive environment to support neuron regeneration. CONCLUSION: The
      ASN-BDNF transplantation provided a promising therapeutic approach to promote
      axonal regeneration and recovery after SCI, and can be used as part of a
      combinatory treatment strategy for SCI management.

PMID- 22952612
TI  - Early emergence and selection of a SIV-LTR C/EBP site variant in SIV-infected
      macaques that increases virus infectivity.
AB  - CCAAT/enhancer binding protein (C/EBP)beta, and C/EBP binding sites in the
      HIV/SIV-long terminal repeat (LTR) are crucial for regulating transcription and
      for IFNbeta-mediated suppression of virus replication in macrophages, the
      predominant source of productive virus replication in the brain. We investigated
      sequence variation within the SIV-LTR C/EBP sites that may be under selective
      pressure in vivo and therefore associated with disease progression. Using the SIV
      macaque model, we examined viral LTR sequences derived from the spleen, a site of
      macrophage and lymphocyte infection, and the brain from macaques euthanized at
      10, 21, 42, 48 and 84 days postinoculation (p.i.). A dominant variant, DS1C/A,
      containing an adenine-to-guanine substitution and a linked cytosine-to-adenine
      substitution in the downstream (DS1) C/EBP site, was detected in the spleen at 10
      days p.i. The DS1C/A genotype was not detected in the brain until 42 days p.i.,
      after which it was the predominant replicating genotype in both brain and spleen.
      Functional characterization of the DS1C/A containing SIV showed increased
      infectivity with or without IFNbeta treatment over the wild-type virus, SIV/17E
      Fr. The DS1C/A C/EBP site had higher affinity for both protein isoforms of
      C/EBPbeta compared to the wild-type DS1 C/EBP site. Cytokine expression in spleen
      compared to brain implicated IFNbeta and IL-6 responses as part of the selective
      pressures contributing to emergence of the DS1C/A genotype in vivo. These studies
      demonstrate selective replication of virus containing the DS1C/A genotype that
      either emerges very early in spleen and spreads to the brain, or evolves
      independently in the brain when IFNbeta and IL-6 levels are similar to that found
      in spleen earlier in infection.

PMID- 22952614
TI  - P wave dispersion and maximum P wave duration are independently associated with
      rapid renal function decline.
AB  - The P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly
      used as noninvasive tools to assess for left atrial enlargement. There are
      limited studies to evaluate whether P wave parameters are independently
      associated with decline in renal function. Accordingly, the aim of this study is
      to assess whether P wave parameters are independently associated with progression
      to renal end point of >=25% decline in estimated glomerular filtration rate
      (eGFR). This longitudinal study included 166 patients. The renal end point was
      defined as >=25% decline in eGFR. We measured two ECG P wave parameters corrected
      by heart rate, i.e. corrected P wave dispersion (PWdisperC) and corrected P wave
      maximum duration (PWdurMaxC). Heart function and structure were measured from
      echocardiography. Clinical data, P wave parameters, and echocardiographic
      measurements were compared and analyzed. Forty-three patients (25.9%) reached
      renal end point. Kaplan-Meier curves for renal end point-free survival showed
      PWdisperC > median (63.0 ms) (log-rank P = 0.004) and PWdurMaxC > median (117.9
      ms) (log-rank P<0.001) were associated with progression to renal end point.
      Multivariate forward Cox-regression analysis identified increased PWdisperC
      (hazard ratio [HR], 1.024; P = 0.001) and PWdurMaxC (HR, 1.029; P = 0.001) were
      independently associated with progression to renal end point. Our results
      demonstrate that increased PWdisperC and PWdurMaxC were independently associated
      with progression to renal end point. Screening patients by means of PWdisperC and
      PWdurMaxC on 12 lead ECG may help identify a high risk group of rapid renal
      function decline.

PMID- 22952615
TI  - Reviews of functional MRI: the ethical dimensions of methodological critique.
AB  - Neuroimaging studies involving human subjects raise a range of ethics issues.
      Many of these issues are heightened in the context of neuroimaging research
      involving persons with mental health disorders. There has been growing interest
      in these issues among legal scholars, philosophers, social scientists, and as
      well as neuroimagers over the last decade. Less clear, however, is the extent to
      which members of the neuroimaging community are engaged with these issues when
      they undertake their research and report results. In this study, we analyze the
      peer-reviewed review literature involving fMRI as applied to the study of mental
      health disorders. Our hypothesis is that, due to the critical orientation of
      reviews, and the vulnerability of mental health population, the penetrance of
      neuroethics will be higher in the review literature in this area than it is in
      the primary fMRI research literature more generally. We find that while authors
      of reviews do focus a great deal of attention on the methodological limitations
      of the studies they discussed, contrary to our hypothesis, they do not frame
      concerns in ethical terms despite their ethical significance. We argue that an
      ethics lens on such discussion would increase the knowledge-value of this
      scholarly work.

PMID- 22952616
TI  - Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic
      acid, host cell adherence, invasion, and in vivo colonization.
AB  - The recently identified type VI secretion system (T6SS) of proteobacteria has
      been shown to promote pathogenicity, competitive advantage over competing
      microorganisms, and adaptation to environmental perturbation. By detailed
      phenotypic characterization of loss-of-function mutants, in silico, in vitro and
      in vivo analyses, we provide evidence that the enteric pathogen, Campylobacter
      jejuni, possesses a functional T6SS and that the secretion system exerts
      pleiotropic effects on two crucial processes--survival in a bile salt,
      deoxycholic acid (DCA), and host cell adherence and invasion. The expression of
      T6SS during initial exposure to the upper range of physiological levels of DCA
      (0.075%-0.2%) was detrimental to C. jejuni proliferation, whereas down-regulation
      or inactivation of T6SS enabled C. jejuni to resist this effect. The C. jejuni
      multidrug efflux transporter gene, cmeA, was significantly up-regulated during
      the initial exposure to DCA in the wild type C. jejuni relative to the T6SS
      deficient strains, suggesting that inhibition of proliferation is the consequence
      of T6SS-mediated DCA influx. A sequential modulation of the efflux transporter
      activity and the T6SS represents, in part, an adaptive mechanism for C. jejuni to
      overcome this inhibitory effect, thereby ensuring its survival. C. jejuni T6SS
      plays important roles in host cell adhesion and invasion as T6SS inactivation
      resulted in a reduction of adherence to and invasion of in vitro cell lines,
      while over-expression of a hemolysin co-regulated protein, which encodes a
      secreted T6SS component, greatly enhanced these processes. When inoculated into
      B6.129P2-IL-10(tm1Cgn) mice, the T6SS-deficient C. jejuni strains did not
      effectively establish persistent colonization, indicating that T6SS contributes
      to colonization in vivo. Taken together, our data demonstrate the importance of
      bacterial T6SS in host cell adhesion, invasion, colonization and, for the first
      time to our knowledge, adaptation to DCA, providing new insights into the role of
      T6SS in C. jejuni pathogenesis.

PMID- 22952617
TI  - Socioeconomic inequality in smoking in low-income and middle-income countries:
      results from the World Health Survey.
AB  - OBJECTIVES: To assess the magnitude and pattern of socioeconomic inequality in
      current smoking in low and middle income countries. METHODS: We used data from
      the World Health Survey [WHS] in 48 low-income and middle-income countries to
      estimate the crude prevalence of current smoking according to household wealth
      quintile. A Poisson regression model with a robust variance was used to generate
      the Relative Index of Inequality [RII] according to wealth within each of the
      countries studied. RESULTS: In males, smoking was disproportionately prevalent in
      the poor in the majority of countries. In numerous countries the poorest men were
      over 2.5 times more likely to smoke than the richest men. Socioeconomic
      inequality in women was more varied showing patterns of both pro-rich and pro
      poor inequality. In 20 countries pro-rich relative socioeconomic inequality was
      statistically significant: the poorest women had a higher prevalence of smoking
      compared to the richest women. Conversely, in 9 countries women in the richest
      population groups had a statistically significant greater risk of smoking
      compared to the poorest groups. CONCLUSION: Both the pattern and magnitude of
      relative inequality may vary greatly between countries. Prevention measures
      should address the specific pattern of smoking inequality observed within a
      population.

PMID- 22952618
TI  - Prioritizing key resilience indicators to support coral reef management in a
      changing climate.
AB  - Managing coral reefs for resilience to climate change is a popular concept but
      has been difficult to implement because the empirical scientific evidence has
      either not been evaluated or is sometimes unsupportive of theory, which leads to
      uncertainty when considering methods and identifying priority reefs. We asked
      experts and reviewed the scientific literature for guidance on the multiple
      physical and biological factors that affect the ability of coral reefs to resist
      and recover from climate disturbance. Eleven key factors to inform decisions
      based on scaling scientific evidence and the achievability of quantifying the
      factors were identified. Factors important to resistance and recovery, which are
      important components of resilience, were not strongly related, and should be
      assessed independently. The abundance of resistant (heat-tolerant) coral species
      and past temperature variability were perceived to provide the greatest
      resistance to climate change, while coral recruitment rates, and macroalgae
      abundance were most influential in the recovery process. Based on the 11 key
      factors, we tested an evidence-based framework for climate change resilience in
      an Indonesian marine protected area. The results suggest our evidence-weighted
      framework improved upon existing un-weighted methods in terms of characterizing
      resilience and distinguishing priority sites. The evaluation supports the concept
      that, despite high ecological complexity, relatively few strong variables can be
      important in influencing ecosystem dynamics. This is the first rigorous
      assessment of factors promoting coral reef resilience based on their perceived
      importance, empirical evidence, and feasibility of measurement. There were few
      differences between scientists' perceptions of factor importance and the
      scientific evidence found in journal publications but more before and after
      impact studies will be required to fully test the validity of all the factors.
      The methods here will increase the feasibility and defensibility of including key
      resilience metrics in evaluations of coral reefs, as well as reduce costs.
      Adaptation, marine protected areas, priority setting, resistance, recovery.

PMID- 22952619
TI  - Increased expression levels of WAVE3 are associated with the progression and
      metastasis of triple negative breast cancer.
AB  - BACKGROUND: Breast Cancer (BC) is a heterogeneous disease comprised of at least
      five genetically distinct subtypes, which together form the second leading cause
      of cancer death in women in the United States. Within BC subtypes, those
      classified as Triple Negative BCs (TNBCs) exhibit dismal survival rates due to
      their propensity to develop distant metastases. We have identified the WAVE3
      protein, which is a critical regulator of actin cytoskeleton dynamics that are
      required for the motility and invasion of cancer cells through its activation of
      the Arp2/3 complex, as a key regulator of the different steps of the invasion
      metastasis cascade in BC, especially in the more aggressive TNBCs. Our published
      studies have also shown that elevated expression levels of WAVE3 in the TNBC cell
      lines directly contribute to their increased invasion and metastasis potentials
      both in vitro and in vivo in murine models of BC metastasis.
      METHODOLOGY/PRINCIPAL FINDINGS: Herein, we utilized both immunohistochemistry
      (IHC) of primary human BC tumors as well as quantitative real-time RT-PCR of
      WAVE3 in the peripheral blood of BC patients to clearly establish that WAVE3 is a
      predictive marker of overall BC patients' survival. High levels of WAVE3 were
      predictive for reduced distant recurrence-free survival as well as for decreased
      disease-specific mortality. Our analysis of WAVE3 expression levels in the
      peripheral blood of BC patients showed that WAVE3 is highly expressed in the
      blood of patients who developed metastatic breast cancer compared to those who
      did not. WAVE3 expression was also highly upregulated in the blood of BC patients
      with the more aggressive TNBC subtype. CONCLUSIONS: Together, these findings
      establish WAVE3 as a novel marker for increased risk of breast-cancer-specific
      mortality and for the metastatic potential of the TNBCs, and also identify WAVE3
      as an attractive therapeutic target for the treatment of metastatic BC.

PMID- 22952620
TI  - The impact of asymptomatic helminth co-infection in patients with newly diagnosed
      tuberculosis in north-west Ethiopia.
AB  - BACKGROUND: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to
      a large extent overlapping. The aim of this study was to assess the impact of
      asymptomatic helminth infection on the immunological response among TB patients
      with and without HIV, their house hold contacts and community controls.
      METHODOLOGY: Consecutive smear positive TB patients (n = 112), their household
      contacts (n = 71) and community controls (n = 112) were recruited in Gondar town,
      Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4
      counts were performed and tuberculosis patients were followed up for 3 months
      after initiation of anti-TB treatment. RESULTS: Helminth co-infection rate was
      29% in TB patients and 21% in both community control and household contacts (p =
      0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients
      the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level
      were significantly associated with asymptomatic helminth infection. During TB
      treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32)
      at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV-/TB patients showed
      no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was
      stable at week 8 and 12 as well. CONCLUSION: One third of smear positive TB
      patients were infected with helminths. Eosinophilia and elevated IgE level
      correlated with asymptomatic worm infection, indicating an effect on host
      immunity. The rate of worm infection declined during TB treatment in HIV+/TB co
      infected patients whereas no decline was seen in HIV-/TB group.

PMID- 22952621
TI  - Comparative transcriptome analysis of two olive cultivars in response to NaCl
      stress.
AB  - BACKGROUND: Olive (Olea europaea L.) cultivation is rapidly expanding and low
      quality saline water is often used for irrigation. The molecular basis of salt
      tolerance in olive, though, has not yet been investigated at a system level. In
      this study a comparative transcriptomics approach was used as a tool to unravel
      gene regulatory networks underlying salinity response in olive trees by
      simulating as much as possible olive growing conditions in the field.
      Specifically, we investigated the genotype-dependent differences in the
      transcriptome response of two olive cultivars, a salt-tolerant and a salt
      sensitive one. METHODOLOGY/PRINCIPAL FINDINGS: A 135-day long salinity experiment
      was conducted using one-year old trees exposed to NaCl stress for 90 days
      followed by 45 days of post-stress period during the summer. A cDNA library made
      of olive seedling mRNAs was sequenced and an olive microarray was constructed.
      Total RNA was extracted from root samples after 15, 45 and 90 days of NaCl
      treatment as well as after 15 and 45 days of post-treatment period and used for
      microarray hybridizations. SAM analysis between the NaCl-stress and the post
      stress time course resulted in the identification of 209 and 36 differentially
      expressed transcripts in the salt-tolerant and salt-sensitive cultivar,
      respectively. Hierarchical clustering revealed two major, distinct clusters for
      each cultivar. Despite the limited number of probe sets, transcriptional
      regulatory networks were constructed for both cultivars while several
      hierarchically-clustered interacting transcription factor regulators such as JERF
      and bZIP homologues were identified. CONCLUSIONS/SIGNIFICANCE: A systems biology
      approach was used and differentially expressed transcripts as well as regulatory
      interactions were identified. The comparison of the interactions among
      transcription factors in olive with those reported for Arabidopsis might indicate
      similarities in the response of a tree species with Arabidopsis at the
      transcriptional level under salinity stress.

PMID- 22952622
TI  - Omentin-1 is decreased in maternal plasma, placenta and adipose tissue of women
      with pre-existing obesity.
AB  - OBJECTIVE: The aim of this study was to determine (i) the effect of maternal
      obesity and gestational diabetes mellitus (GDM) on (i) the circulating levels of
      omentin-1 in cord and maternal plasma, and (ii) gene expression and release of
      omentin-1 from human placenta and adipose tissue. The effect of pregnancy on
      circulating omentin-1 levels was also determined. DESIGN: Omentin-1 levels were
      measured in maternal and cord plasma from obese and non-obese normal glucose
      tolerant women (NGT; n = 44) and women with GDM (n = 39) at the time of term
      elective Caesarean section. Placenta and adipose tissue expression and release of
      omentin-1 was measured from 22 NGT and 22 GDM women collected at the time of term
      elective Caesarean section. Omentin-1 levels were also measured in maternal
      plasma from 13 NGT women at 11 and 28 weeks gestation and 7 weeks postpartum.
      RESULTS: Maternal obesity was associated with significantly lower omentin-1
      levels in maternal plasma; however, there was no effect of maternal obesity on
      cord omentin levels. Omentin-1 gene expression was lower in placenta and adipose
      tissue obtained from women with pre-existing obesity. In addition to this,
      adipose tissue release of omentin-1 was significantly lower from obese pregnant
      women. Omentin-1 levels were significantly lower in non-obese GDM compared to non
      obese NGT women. However, there was no difference in omentin-1 levels between
      obese NGT and obese GDM women. There was no effect of GDM on cord omentin levels,
      and placental and adipose tissue omentin-1 expression. Maternal omentin-1 levels
      were negatively correlated with fetal birthweight and fetal ponderal index.
      CONCLUSIONS: The data presented in this study demonstrate that pre-existing
      maternal obesity is associated with lower omentin-1 expression in placenta,
      adipose tissue and maternal plasma. Alteration in omentin-1 in pregnancy may
      influence the development of metabolic disorders in offspring later in life.

PMID- 22952623
TI  - U-curve association between timing of renal replacement therapy initiation and in
      hospital mortality in postoperative acute kidney injury.
AB  - BACKGROUND: Postoperative acute kidney injury (AKI) is associated with poor
      outcomes in surgical patients. This study aims to evaluate whether the timing of
      renal replacement therapy (RRT) initiation affects the in-hospital mortality of
      patients with postoperative AKI. METHODOLOGY: This multicenter retrospective
      observational study, which was conducted in the intensive care units (ICUs) in a
      tertiary hospital (National Taiwan University Hospital) and its branch hospitals
      in Taiwan between January, 2002, and April, 2009, included adult patients with
      postoperative AKI who underwent RRT for predefined indications. The demographic
      data, comorbid diseases, types of surgery and RRT, and the indications for RRT
      were documented. Patients were categorized according to the period of time
      between the ICU admission and RRT initiation as the early (EG, ?1 day),
      intermediate (IG, 2-3 days), and late (LG, ?4 days) groups. The in-hospital
      mortality rate censored at 180 day was defined as the endpoint. RESULTS: Six
      hundred forty-eight patients (418 men, mean age 63.0+/-15.9 years) were enrolled,
      and 379 patients (58.5%) died during the hospitalization. Both the estimated
      probability of death and the in-hospital mortality rates of the three groups
      represented U-curves. According to the Cox proportional hazard method, LG (hazard
      ratio, 1.527; 95% confidence interval, 1.152-2.024; P = 0.003, compared with IG
      group), age (1.014; 1.006-1.021), diabetes (1.279; 1.022-1.601; P = 0.031),
      cirrhosis (2.147; 1.421-3.242), extracorporeal membrane oxygenation support
      (1.811; 1.391-2.359), initial neurological dysfunction (1.448; 1.107-1.894; P =
      0.007), pre-RRT mean arterial pressure (0.988; 0.981-0.995), inotropic equivalent
      (1.006; 1.001-1.012; P = 0.013), APACHE II scores (1.055; 1.037-1.073), and
      sepsis (1.939; 1.536-2.449) were independent predictors of the in-hospital
      mortality (All P<0.001 except otherwise stated). CONCLUSIONS: The current study
      found a U-curve association between the timing of the RRT initiation after the
      ICU admission and patients' in-hospital mortalities, and alerts physicians of
      certain factors affecting the outcome after the RRT initiation.

PMID- 22952624
TI  - Brain networks of explicit and implicit learning.
AB  - Are explicit versus implicit learning mechanisms reflected in the brain as
      distinct neural structures, as previous research indicates, or are they
      distinguished by brain networks that involve overlapping systems with
      differential connectivity? In this functional MRI study we examined the neural
      correlates of explicit and implicit learning of artificial grammar sequences.
      Using effective connectivity analyses we found that brain networks of different
      connectivity underlie the two types of learning: while both processes involve
      activation in a set of cortical and subcortical structures, explicit learners
      engage a network that uses the insula as a key mediator whereas implicit learners
      evoke a direct frontal-striatal network. Individual differences in working memory
      also differentially impact the two types of sequence learning.

PMID- 22952625
TI  - HIV-1 genetic diversity and transmitted drug resistance mutations among patients
      from the North, Central and South regions of Angola.
AB  - BACKGROUND: Angola presents a very complex HIV-1 epidemic characterized by the co
      circulation of several HIV-1 group M subtypes, intersubtype recombinants and
      unclassified (U) variants. The viral diversity outside the major metropolitan
      regions (Luanda and Cabinda) and the prevalence of transmitted drug resistance
      mutations (DRM) since the introduction of HAART in 2004, however, has been barely
      studied. METHODS: One hundred and one individuals from the Central (n = 44),
      North (n = 35), and South (n = 22) regions of Angola were diagnosed as HIV-1
      positive and had their blood collected between 2008 and 2010, at one of the
      National Referral Centers for HIV diagnosis, the Kifangondo Medical Center,
      located in the border between the Luanda and Bengo provinces. Angolan samples
      were genotyped based on phylogenetic and bootscanning analyses of the pol (PR/RT)
      gene and their drug resistance profile was analyzed. RESULTS: Among the 101
      samples analyzed, 51% clustered within a pure group M subtype, 42% were
      classified as intersubtype recombinants, and 7% were denoted as U. We observed an
      important variation in the prevalence of different HIV-1 genetic variants among
      country regions, with high frequency of subtype F1 in the North (20%),
      intersubtype recombinants in the Central (42%), and subtype C in the South (45%).
      Statistically significant difference in HIV-1 clade distribution was only
      observed in subtype C prevalence between North vs South (p = 0.0005) and Central
      vs South (p = 0.0012) regions. DRM to NRTI and/or NNRTI were detected in 16.3% of
      patients analyzed. CONCLUSIONS: These results demonstrate a heterogeneous
      distribution of HIV-1 genetic variants across different regions in Angola and
      also revealed an unexpected high frequency of DRM to RT inhibitors in patients
      that have reported no antiretroviral usage, which may decrease the efficiency of
      the standard first-line antiretroviral regimens currently used in the country.

PMID- 22952626
TI  - Comparing GIS-based measures in access to mammography and their validity in
      predicting neighborhood risk of late-stage breast cancer.
AB  - BACKGROUND: Assessing neighborhood environment in access to mammography remains a
      challenge when investigating its contextual effect on breast cancer-related
      outcomes. Studies using different Geographic Information Systems (GIS)-based
      measures reported inconsistent findings. METHODS: We compared GIS-based measures
      (travel time, service density, and a two-Step Floating Catchment Area method
      [2SFCA]) of access to FDA-accredited mammography facilities in terms of their
      Spearman correlation, agreement (Kappa) and spatial patterns. As an indicator of
      predictive validity, we examined their association with the odds of late-stage
      breast cancer using cancer registry data. RESULTS: The accessibility measures
      indicated considerable variation in correlation, Kappa and spatial pattern.
      Measures using shortest travel time (or average) and service density showed low
      correlations, no agreement, and different spatial patterns. Both types of
      measures showed low correlations and little agreement with the 2SFCA measures. Of
      all measures, only the two measures using 6-timezone-weighted 2SFCA method were
      associated with increased odds of late-stage breast cancer (quick-distance-decay:
      odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.01-1.32; slow-distance
      decay: OR = 1.19, 95% CI = 1.03-1.37) after controlling for demographics and
      neighborhood socioeconomic deprivation. CONCLUSIONS: Various GIS-based measures
      of access to mammography facilities exist and are not identical in principle and
      their association with late-stage breast cancer risk. Only the two measures using
      the 2SFCA method with 6-timezone weighting were associated with increased odds of
      late-stage breast cancer. These measures incorporate both travel barriers and
      service competition. Studies may observe different results depending on the
      measure of accessibility used.

PMID- 22952627
TI  - Analysis of an inactive cyanobactin biosynthetic gene cluster leads to discovery
      of new natural products from strains of the genus Microcystis.
AB  - Cyanobactins are cyclic peptides assembled through the cleavage and modification
      of short precursor proteins. An inactive cyanobactin gene cluster has been
      described from the genome Microcystis aeruginosa NIES843. Here we report the
      discovery of active counterparts in strains of the genus Microcystis guided by
      this silent cyanobactin gene cluster. The end products of the gene clusters were
      structurally diverse cyclic peptides, which we named piricyclamides. Some of the
      piricyclamides consisted solely of proteinogenic amino acids while others
      contained disulfide bridges and some were prenylated or geranylated. The
      piricyclamide gene clusters encoded between 1 and 4 precursor genes. They encoded
      highly diverse core peptides ranging in length from 7-17 amino acids with just a
      single conserved amino acid. Heterologous expression of the pir gene cluster from
      Microcystis aeruginosa PCC7005 in Escherichia coli confirmed that this gene
      cluster is responsible for the biosynthesis of piricyclamides. Chemical analysis
      demonstrated that Microcystis strains could produce an array of piricyclamides
      some of which are geranylated or prenylated. The genetic diversity of
      piricyclamides in a bloom sample was explored and 19 different piricyclamide
      precursor genes were found. This study provides evidence for a stunning array of
      piricyclamides in Microcystis, a worldwide occurring bloom forming cyanobacteria.

PMID- 22952628
TI  - Structures of human DPP7 reveal the molecular basis of specific inhibition and
      the architectural diversity of proline-specific peptidases.
AB  - Proline-specific dipeptidyl peptidases (DPPs) are emerging targets for drug
      development. DPP4 inhibitors are approved in many countries, and other dipeptidyl
      peptidases are often referred to as DPP4 activity- and/or structure-homologues
      (DASH). Members of the DASH family have overlapping substrate specificities, and,
      even though they share low sequence identity, therapeutic or clinical cross
      reactivity is a concern. Here, we report the structure of human DPP7 and its
      complex with a selective inhibitor Dab-Pip (L-2,4-diaminobutyryl-piperidinamide)
      and compare it with that of DPP4. Both enzymes share a common catalytic domain
      (alpha/beta-hydrolase). The catalytic pocket is located in the interior of DPP7,
      deep inside the cleft between the two domains. Substrates might access the active
      site via a narrow tunnel. The DPP7 catalytic triad is completely conserved and
      comprises Ser162, Asp418 and His443 (corresponding to Ser630, Asp708 and His740
      in DPP4), while other residues lining the catalytic pockets differ considerably.
      The "specificity domains" are structurally also completely different exhibiting a
      beta-propeller fold in DPP4 compared to a rare, completely helical fold in DPP7.
      Comparing the structures of DPP7 and DPP4 allows the design of specific
      inhibitors and thus the development of less cross-reactive drugs. Furthermore,
      the reported DPP7 structures shed some light onto the evolutionary relationship
      of prolyl-specific peptidases through the analysis of the architectural
      organization of their domains.

PMID- 22952629
TI  - Unique features of odorant-binding proteins of the parasitoid wasp Nasonia
      vitripennis revealed by genome annotation and comparative analyses.
AB  - Insects are the most diverse group of animals on the planet, comprising over 90%
      of all metazoan life forms, and have adapted to a wide diversity of ecosystems in
      nearly all environments. They have evolved highly sensitive chemical senses that
      are central to their interaction with their environment and to communication
      between individuals. Understanding the molecular bases of insect olfaction is
      therefore of great importance from both a basic and applied perspective. Odorant
      binding proteins (OBPs) are some of most abundant proteins found in insect
      olfactory organs, where they are the first component of the olfactory
      transduction cascade, carrying odorant molecules to the olfactory receptors. We
      carried out a search for OBPs in the genome of the parasitoid wasp Nasonia
      vitripennis and identified 90 sequences encoding putative OBPs. This is the
      largest OBP family so far reported in insects. We report unique features of the
      N. vitripennis OBPs, including the presence and evolutionary origin of a new
      subfamily of double-domain OBPs (consisting of two concatenated OBP domains), the
      loss of conserved cysteine residues and the expression of pseudogenes. This study
      also demonstrates the extremely dynamic evolution of the insect OBP family: (i)
      the number of different OBPs can vary greatly between species; (ii) the sequences
      are highly diverse, sometimes as a result of positive selection pressure with
      even the canonical cysteines being lost; (iii) new lineage specific domain
      arrangements can arise, such as the double domain OBP subfamily of wasps and
      mosquitoes.

PMID- 22952630
TI  - P2RX7: expression responds to sleep deprivation and associates with rapid cycling
      in bipolar disorder type 1.
AB  - CONTEXT: Rapid cycling is a severe form of bipolar disorder with an increased
      rate of episodes that is particularly treatment-responsive to chronotherapy and
      stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected
      by sleep deprivation and be implicated in rapid cycling. OBJECTIVES: To assess
      whether P2RX7 expression is affected by total sleep deprivation and if variation
      in P2RX7 is associated with rapid cycling in bipolar patients. DESIGN: Gene
      expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy
      volunteers and case-case and case-control SNP/haplotype association analyses in
      patients. PARTICIPANTS: Healthy volunteers at the sleep research center,
      University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish
      outpatients recruited from specialized psychiatric clinics for bipolar disorder,
      diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and
      anonymous blood donor controls (n = 1,044). RESULTS: P2RX7 RNA levels were
      significantly increased during sleep deprivation in PBMCs from healthy volunteers
      (p = 2.3*10(-9)). The P2RX7 rs2230912 _A allele was more common (OR = 2.2, p =
      0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the
      protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common,
      among rapid cycling cases compared to non-rapid cycling bipolar patients and
      blood donor controls. CONCLUSIONS: Sleep deprivation increased P2RX7 expression
      in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A
      variant was associated with rapid cycling in bipolar disorder. This supports
      earlier findings of P2RX7 associations to affective disorder and is in agreement
      with that particularly rapid cycling patients have a more vulnerable diurnal
      system.

PMID- 22952631
TI  - Sex, lies and fMRI--gender differences in neural basis of deception.
AB  - Deception has always been a part of human communication as it helps to promote
      self-presentation. Although both men and women are equally prone to try to manage
      their appearance, their strategies, motivation and eagerness may be different.
      Here, we asked if lying could be influenced by gender on both the behavioral and
      neural levels. To test whether the hypothesized gender differences in brain
      activity related to deceptive responses were caused by differential socialization
      in men and women, we administered the Gender Identity Inventory probing the
      participants' subjective social sex role. In an fMRI session, participants were
      instructed either to lie or to tell the truth while answering a questionnaire
      focusing on general and personal information. Only for personal information, we
      found differences in neural responses during instructed deception in men and
      women. The women vs. men direct contrast revealed no significant differences in
      areas of activation, but men showed higher BOLD signal compared to women in the
      left middle frontal gyrus (MFG). Moreover, this effect remained unchanged when
      self-reported psychological gender was controlled for. Thus, our study showed
      that gender differences in the neural processes engaged during falsifying
      personal information might be independent from socialization.

PMID- 22952632
TI  - A deletion in the bovine FANCI gene compromises fertility by causing fetal death
      and brachyspina.
AB  - Fertility is one of the most important traits in dairy cattle, and has been
      steadily declining over the last decades. We herein use state-of-the-art genomic
      tools, including high-throughput SNP genotyping and next-generation sequencing,
      to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome
      (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that
      despite the very low incidence of BS (<1/100,000), carrier frequency is as high
      as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is
      likely due to the fact that a large proportion of homozygous mutant calves die
      during pregnancy. We postulate that several other embryonic lethals may segregate
      in livestock and significantly compromise fertility, and propose a genotype
      driven screening strategy to detect the corresponding deleterious mutations.

PMID- 22952633
TI  - Rapid diagnostic tests for malaria diagnosis in the Peruvian Amazon: impact of
      pfhrp2 gene deletions and cross-reactions.
AB  - BACKGROUND: In the Peruvian Amazon, Plasmodium falciparum and Plasmodium vivax
      malaria are endemic in rural areas, where microscopy is not available. Malaria
      rapid diagnostic tests (RDTs) provide quick and accurate diagnosis. However,
      pfhrp2 gene deletions may limit the use of histidine-rich protein-2 (PfHRP2)
      detecting RDTs. Further, cross-reactions of P. falciparum with P. vivax-specific
      test lines and vice versa may impair diagnostic specificity. METHODS: Thirteen
      RDT products were evaluated on 179 prospectively collected malaria positive
      samples. Species diagnosis was performed by microscopy and confirmed by PCR.
      Pfhrp2 gene deletions were assessed by PCR. RESULTS: Sensitivity for P.
      falciparum diagnosis was lower for PfHRP2 compared to P. falciparum-specific
      Plasmodium lactate dehydrogenase (Pf-pLDH)-detecting RDTs (71.6% vs. 98.7%,
      p<0.001). Most (19/21) false negative PfHRP2 results were associated with pfhrp2
      gene deletions (25.7% of 74 P. falciparum samples). Diagnostic sensitivity for P.
      vivax (101 samples) was excellent, except for two products. In 10/12 P. vivax
      detecting RDT products, cross-reactions with the PfHRP2 or Pf-pLDH line occurred
      at a median frequency of 2.5% (range 0%-10.9%) of P. vivax samples assessed. In
      two RDT products, two and one P. falciparum samples respectively cross-reacted
      with the Pv-pLDH line. Two Pf-pLDH/pan-pLDH-detecting RDTs showed excellent
      sensitivity with few (1.0%) cross-reactions but showed faint Pf-pLDH lines in
      24.7% and 38.9% of P. falciparum samples. CONCLUSION: PfHRP2-detecting RDTs are
      not suitable in the Peruvian Amazon due to pfhrp2 gene deletions. Two Pf-pLDH
      detecting RDTs performed excellently and are promising RDTs for this region
      although faint test lines are of concern.

PMID- 22952634
TI  - Planning of ballistic movement following stroke: insights from the startle
      reflex.
AB  - Following stroke, reaching movements are slow, segmented, and variable. It is
      unclear if these deficits result from a poorly constructed movement plan or an
      inability to voluntarily execute an appropriate plan. The acoustic startle reflex
      provides a means to initiate a motor plan involuntarily. In the presence of a
      movement plan, startling acoustic stimulus triggers non-voluntary early execution
      of planned movement, a phenomenon known as the startReact response. In unimpaired
      individuals, the startReact response is identical to a voluntarily initiated
      movement, except that it is elicited 30-40 ms. As the startReact response is
      thought to be mediated by brainstem pathways, we hypothesized that the startReact
      response is intact in stroke subjects. If startReact is intact, it may be
      possible to elicit more task-appropriate patterns of muscle activation than can
      be elicited voluntarily. We found that startReact responses were intact following
      stroke. Responses were initiated as rapidly as those in unimpaired subjects, and
      with muscle coordination patterns resembling those seen during unimpaired
      volitional movements. Results were striking for elbow flexion movements, which
      demonstrated no significant differences between the startReact responses elicited
      in our stroke and unimpaired subject groups. The results during planned extension
      movements were less straightforward for stroke subjects, since the startReact
      response exhibited task inappropriate activity in the flexors. This inappropriate
      activity diminished over time. This adaptation suggests that the inappropriate
      activity was transient in nature and not related to the underlying movement plan.
      We hypothesize that the task-inappropriate flexor activity during extension
      results from an inability to suppress the classic startle reflex, which primarily
      influences flexor muscles and adapts rapidly with successive stimuli. These
      results indicate that stroke subjects are capable of planning ballistic elbow
      movements, and that when these planned movements are involuntarily executed they
      can be as rapid and appropriate as those in unimpaired individuals.

PMID- 22952636
TI  - Focusing on attention: the effects of working memory capacity and load on
      selective attention.
AB  - BACKGROUND: Working memory (WM) is imperative for effective selective attention.
      Distractibility is greater under conditions of high (vs. low) concurrent working
      memory load (WML), and in individuals with low (vs. high) working memory capacity
      (WMC). In the current experiments, we recorded the flanker task performance of
      individuals with high and low WMC during low and high WML, to investigate the
      combined effect of WML and WMC on selective attention. METHODOLOGY/PRINCIPAL
      FINDINGS: In Experiment 1, distractibility from a distractor at a fixed distance
      from the target was greater when either WML was high or WMC was low, but
      surprisingly smaller when both WML was high and WMC low. Thus we observed an
      inverted-U relationship between reductions in WM resources and distractibility.
      In Experiment 2, we mapped the distribution of spatial attention as a function of
      WMC and WML, by recording distractibility across several target-to-distractor
      distances. The pattern of distractor effects across the target-to-distractor
      distances demonstrated that the distribution of the attentional window becomes
      dispersed as WM resources are limited. The attentional window was more spread out
      under high compared to low WML, and for low compared to high WMC individuals, and
      even more so when the two factors co-occurred (i.e., under high WML in low WMC
      individuals). The inverted-U pattern of distractibility effects in Experiment 1,
      replicated in Experiment 2, can thus be explained by differences in the spread of
      the attentional window as a function of WM resource availability.
      CONCLUSIONS/SIGNIFICANCE: The current findings show that limitations in WM
      resources, due to either WML or individual differences in WMC, affect the spatial
      distribution of attention. The difference in attentional constraining between
      high and low WMC individuals demonstrated in the current experiments helps
      characterise the nature of previously established associations between WMC and
      controlled attention.

PMID- 22952635
TI  - Creation of an open-access, mutation-defined fibroblast resource for neurological
      disease research.
AB  - Our understanding of the molecular mechanisms of many neurological disorders has
      been greatly enhanced by the discovery of mutations in genes linked to familial
      forms of these diseases. These have facilitated the generation of cell and animal
      models that can be used to understand the underlying molecular pathology.
      Recently, there has been a surge of interest in the use of patient-derived cells,
      due to the development of induced pluripotent stem cells and their subsequent
      differentiation into neurons and glia. Access to patient cell lines carrying the
      relevant mutations is a limiting factor for many centres wishing to pursue this
      research. We have therefore generated an open-access collection of fibroblast
      lines from patients carrying mutations linked to neurological disease. These cell
      lines have been deposited in the National Institute for Neurological Disorders
      and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and
      can be requested by any research group for use in in vitro disease modelling.
      There are currently 71 mutation-defined cell lines available for request from a
      wide range of neurological disorders and this collection will be continually
      expanded. This represents a significant resource that will advance the use of
      patient cells as disease models by the scientific community.

PMID- 22952637
TI  - Linking influenza virus tissue tropism to population-level reproductive fitness.
AB  - Influenza virus tissue tropism defines the host cells and tissues that support
      viral replication and contributes to determining which regions of the respiratory
      tract are infected in humans. The location of influenza virus infection along the
      respiratory tract is a key determinant of virus pathogenicity and
      transmissibility, which are at the basis of influenza burdens in the human
      population. As the pathogenicity and transmissibility of influenza virus
      ultimately determine its reproductive fitness at the population level, strong
      selective pressures will shape influenza virus tissue tropisms that maximize
      fitness. At present, the relationships between influenza virus tissue tropism
      within hosts and reproductive fitness at the population level are poorly
      understood. The selective pressures and constraints that shape tissue tropism and
      thereby influence the location of influenza virus infection along the respiratory
      tract are not well characterized. We use mathematical models that link within
      host infection dynamics in a spatially-structured human respiratory tract to
      between-host transmission dynamics, with the aim of characterizing the possible
      selective pressures on influenza virus tissue tropism. The results indicate that
      spatial heterogeneities in virus clearance, virus pathogenicity or both,
      resulting from the unique structure of the respiratory tract, may drive optimal
      receptor binding affinity--that maximizes influenza virus reproductive fitness at
      the population level--towards sialic acids with alpha2,6 linkage to galactose.
      The expanding cell pool deeper down the respiratory tract, in association with
      lower clearance rates, may result in optimal infectivity rates--that likewise
      maximize influenza virus reproductive fitness at the population level--to exhibit
      a decreasing trend towards deeper regions of the respiratory tract. Lastly, pre
      existing immunity may drive influenza virus tissue tropism towards upper regions
      of the respiratory tract. The proposed framework provides a new template for the
      cross-scale study of influenza virus evolutionary and epidemiological dynamics in
      humans.

PMID- 22952638
TI  - Toll-like receptor (TLR2 and TLR4) polymorphisms and chronic obstructive
      pulmonary disease.
AB  - Toll-like receptors (TLRs) participate in the defence against bacterial
      infections that are common in patients with Chronic Obstructive Pulmonary Disease
      (COPD). We studied all tagging SNPs in TLR2 and TLR4 and their associations with
      the level and change over time of both FEV(1) and sputum inflammatory cells in
      moderate-to-severe COPD. Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110
      COPD patients. Associations of SNPs with lung function and inflammatory cells in
      induced sputum were analyzed cross-sectionally with linear regression and
      longitudinally with linear mixed-effect models. Two SNPs in TLR2 (rs1898830 and
      rs11938228) were associated with a lower level of FEV(1) and accelerated decline
      of FEV(1) and higher numbers of sputum inflammatory cells. None of the TLR4 SNPs
      was associated with FEV(1) level. Eleven out of 17 SNPs were associated with
      FEV(1) decline, including rs12377632 and rs10759931, which were additionally
      associated with higher numbers of sputum inflammatory cells at baseline and with
      increase over time. This is the first longitudinal study showing that tagging
      SNPs in TLR2 and TLR4 are associated with the level and decline of lung function
      as well as with inflammatory cell numbers in induced sputum in COPD patients,
      suggesting a role in the severity and progression of COPD.

PMID- 22952639
TI  - 29 mammalian genomes reveal novel exaptations of mobile elements for likely
      regulatory functions in the human genome.
AB  - Recent research supports the view that changes in gene regulation, as opposed to
      changes in the genes themselves, play a significant role in morphological
      evolution. Gene regulation is largely dependent on transcription factor binding
      sites. Researchers are now able to use the available 29 mammalian genomes to
      measure selective constraint at the level of binding sites. This detailed map of
      constraint suggests that mammalian genomes co-opt fragments of mobile elements to
      act as gene regulatory sequence on a large scale. In the human genome we detect
      over 280,000 putative regulatory elements, totaling approximately 7 Mb of
      sequence, that originated as mobile element insertions. These putative regulatory
      regions are conserved non-exonic elements (CNEEs), which show considerable cross
      species constraint and signatures of continued negative selection in humans, yet
      do not appear in a known mature transcript. These putative regulatory elements
      were co-opted from SINE, LINE, LTR and DNA transposon insertions. We demonstrate
      that at least 11%, and an estimated 20%, of gene regulatory sequence in the human
      genome showing cross-species conservation was co-opted from mobile elements. The
      location in the genome of CNEEs co-opted from mobile elements closely resembles
      that of CNEEs in general, except in the centers of the largest gene deserts where
      recognizable co-option events are relatively rare. We find that regions of
      certain mobile element insertions are more likely to be held under purifying
      selection than others. In particular, we show 6 examples where paralogous
      instances of an often co-opted mobile element region define a sequence motif that
      closely matches a transcription factor's binding profile.

PMID- 22952640
TI  - Controlling HIV epidemics among injection drug users: eight years of Cross-Border
      HIV prevention interventions in Vietnam and China.
AB  - INTRODUCTION: HIV in Vietnam and Southern China is driven by injection drug use.
      We have implemented HIV prevention interventions for IDUs since 2002-2003 in Lang
      Son and Ha Giang Provinces, Vietnam and Ning Ming County (Guangxi), China.
      METHODS: Interventions provide peer education and needle/syringe distribution.
      Evaluation employed serial cross-sectional surveys of IDUs 26 waves from 2002 to
      2011, including interviews and HIV testing. Outcomes were HIV risk behaviors, HIV
      prevalence and incidence. HIV incidence estimation used two methods: 1) among new
      injectors from prevalence data; and 2) a capture enzyme immunoassay (BED testing)
      on all HIV+ samples. RESULTS: We found significant declines in drug-related risk
      behaviors and sharp reductions in HIV prevalence among IDUs (Lang Son from 46% to
      23% [p<0.001], Ning Ming: from 17% to 11% [p = 0.003], and Ha Giang: from 51% to
      18% [p<0.001]), reductions not experienced in other provinces without such
      interventions. There were significant declines in HIV incidence to low levels
      among new injectors through 36-48 months, then some rebound, particularly in Ning
      Ming, but BED-based estimates revealed significant reductions in incidence
      through 96 months. DISCUSSION: This is one of the longest studies of HIV
      prevention among IDUs in Asia. The rebound in incidence among new injectors may
      reflect sexual transmission. BED-based estimates may overstate incidence (because
      of false-recent results in patients with long-term infection or on ARV treatment)
      but adjustment for false-recent results and survey responses on duration of
      infection generally confirm BED-based incidence trends. Combined trends from the
      two estimation methods show sharp declines in incidence to low levels. The
      significant downward trends in all primary outcome measures indicate that the
      Cross-Border interventions played an important role in bringing HIV epidemics
      among IDUs under control. The Cross-Border project offers a model of HIV
      prevention for IDUs that should be considered for large-scale replication.

PMID- 22952641
TI  - Ethnic-specific differences in vitamin D status is associated with adiposity.
AB  - BACKGROUND: Low circulating 25 hydroxyvitamin D [25(OH)D] concentrations are
      common in obesity (BMI >=30 kg/m(2)) and a negative relationship with body fat
      distribution has recently been reported. Ethnic-specific differences in body fat
      distribution have been described with South Asians are reported to have greater
      visceral adipose tissue (VAT), which could influence circulating 25(OH)D
      concentrations. The objective of this study is to investigate the relationship
      between plasma 25(OH)D, adiposity, and body fat distribution in Europeans and
      South Asians. METHODS/PRINCIPAL FINDINGS: 187 Europeans and 192 South Asians were
      assessed for demographics, anthropometrics, and plasma 25(OH)D concentrations.
      Subcutaneous adipose tissue (SAT) and VAT were quantified by CT scan, and percent
      body fat by DEXA. Data were assessed by general linear models. South Asians had
      lower (P<0.001) plasma 25(OH)D concentrations and higher VAT (P = 0.04) than
      Europeans. Plasma 25(OH)D concentrations were negatively (P<0.05) associated with
      BMI, waist circumference, percent body fat, total adipose tissue, VAT, and SAT in
      unadjusted models and negatively (P<0.05) associated with VAT, SAT, and percent
      body fat after adjusting for BMI, ethnicity, age, and season of blood collection
      in males and females. When percent body fat, VAT, and SAT were included in the
      same model, only VAT remained negatively (P<0.05) associated with plasma 25(OH)D
      concentrations. Ethnicity remained significant in all models (P<0.001).
      CONCLUSION: Compared to other adipose tissue compartments, VAT may have a
      distinct role in determining plasma 25(OH)D concentrations, which may account for
      the lower levels in South Asians.

PMID- 22952642
TI  - Malaria control and elimination in Sri Lanka: documenting progress and success
      factors in a conflict setting.
AB  - BACKGROUND: Sri Lanka has a long history of malaria control, and over the past
      decade has had dramatic declines in cases amid a national conflict. A case study
      of Sri Lanka's malaria programme was conducted to characterize the programme and
      explain recent progress. METHODS: The case study employed qualitative and
      quantitative methods. Data were collected from published and grey literature,
      district-level and national records, and thirty-three key informant interviews.
      Expenditures in two districts for two years--2004 and 2009--were compiled.
      FINDINGS: Malaria incidence in Sri Lanka has declined by 99.9% since 1999. During
      this time, there were increases in the proportion of malaria infections due to
      Plasmodium vivax, and the proportion of infections occurring in adult males.
      Indoor residual spraying and distribution of long-lasting insecticide-treated
      nets have likely contributed to the low transmission. Entomological surveillance
      was maintained. A strong passive case detection system captures infections and
      active case detection was introduced. When comparing conflict and non-conflict
      districts, vector control and surveillance measures were maintained in conflict
      areas, often with higher coverage reported in conflict districts. One of two
      districts in the study reported a 48% decline in malaria programme expenditure
      per person at risk from 2004 to 2009. The other district had stable malaria
      spending. CONCLUSIONS/SIGNIFICANCE: Malaria is now at low levels in Sri Lanka-
      124 indigenous cases were found in 2011. The majority of infections occur in
      adult males and are due to P. vivax. Evidence-driven policy and an ability to
      adapt to new circumstances contributed to this decline. Malaria interventions
      were maintained in the conflict districts despite an ongoing war. Sri Lanka has
      set a goal of eliminating malaria by the end of 2014. Early identification and
      treatment of infections, especially imported ones, together with effective
      surveillance and response, will be critical to achieving this goal.

PMID- 22952643
TI  - Specific expression of channelrhodopsin-2 in single neurons of Caenorhabditis
      elegans.
AB  - Optogenetic approaches using light-activated proteins like Channelrhodopsin-2
      (ChR2) enable investigating the function of populations of neurons in live
      Caenorhabditis elegans (and other) animals, as ChR2 expression can be targeted to
      these cells using specific promoters. Sub-populations of these neurons, or even
      single cells, can be further addressed by restricting the illumination to the
      cell of interest. However, this is technically demanding, particularly in free
      moving animals. Thus, it would be helpful if expression of ChR2 could be
      restricted to single neurons or neuron pairs, as even wide-field illumination
      would photostimulate only this particular cell. To this end we adopted the use of
      Cre or FLP recombinases and conditional ChR2 expression at the intersection of
      two promoter expression domains, i.e. in the cell of interest only. Success of
      this method depends on precise knowledge of the individual promoters' expression
      patterns and on relative expression levels of recombinase and ChR2. A bicistronic
      expression cassette with GFP helps to identify the correct expression pattern.
      Here we show specific expression in the AVA reverse command neurons and the
      aversive polymodal sensory ASH neurons. This approach shall enable to generate
      strains for optogenetic manipulation of each of the 302 C. elegans neurons. This
      may eventually allow to model the C. elegans nervous system in its entirety,
      based on functional data for each neuron.

PMID- 22952644
TI  - Tonoplast- and plasma membrane-localized aquaporin-family transporters in blue
      hydrangea sepals of aluminum hyperaccumulating plant.
AB  - Hydrangea (Hydrangea macrophylla) is tolerant of acidic soils in which toxicity
      generally arises from the presence of the soluble aluminum (Al) ion. When
      hydrangea is cultivated in acidic soil, its resulting blue sepal color is caused
      by the Al complex formation of anthocyanin. The concentration of vacuolar Al in
      blue sepal cells can reach levels in excess of approximately 15 mM, suggesting
      the existence of an Al-transport and/or storage system. However, until now, no Al
      transporter has been identified in Al hyperaccumulating plants, animals or
      microorganisms. To identify the transporter being responsible for Al
      hyperaccumulation, we prepared a cDNA library from blue sepals according to the
      sepal maturation stage, and then selected candidate genes using a microarray
      analysis and an in silico study. Here, we identified the vacuolar and plasma
      membrane-localized Al transporters genes vacuolar Al transporter (VALT) and
      plasma membrane Al transporter 1 (PALT1), respectively, which are both members of
      the aquaporin family. The localization of each protein was confirmed by the
      transient co-expression of the genes. Reverse transcription-PCR and
      immunoblotting results indicated that VALT and PALT1 are highly expressed in
      sepal tissue. The overexpression of VALT and PALT1 in Arabidopsis thaliana
      conferred Al-tolerance and Al-sensitivity, respectively.

PMID- 22952645
TI  - Characterization of omental immune aggregates during establishment of a latent
      gammaherpesvirus infection.
AB  - Herpesviruses are characterized by their ability to establish lifelong latent
      infection. The gammaherpesvirus subfamily is distinguished by lymphotropism,
      establishing and maintaining latent infection predominantly in B lymphocytes.
      Consequently, gammaherpesvirus pathogenesis is closely linked to normal B cell
      physiology. Murine gammaherpesvirus 68 (MHV68) pathogenesis in laboratory mice
      has been extensively studied as a model system to gain insights into the nature
      of gammaherpesvirus infection in B cells and their associated lymphoid
      compartments. In addition to B cells, MHV68 infection of macrophages contributes
      significantly to the frequency of viral genome-positive cells in the peritoneal
      cavity throughout latency. The omentum, a sheet of richly-vascularized adipose
      tissue, resides in the peritoneal cavity and contains clusters of immune cell
      aggregates termed milky spots. Although the value of the omentum in surgical
      wound-healing has long been appreciated, the unique properties of this tissue and
      its contribution to both innate and adaptive immunity have only recently been
      recognized. To determine whether the omentum plays a role in gammaherpesvirus
      pathogenesis we examined this site during early MHV68 infection and long-term
      latency. Following intraperitoneal infection, immune aggregates within the
      omentum expanded in size and number and contained virus-infected cells. Notably,
      a germinal-center B cell population appeared in the omentum of infected animals
      with earlier kinetics and greater magnitude than that observed in the spleen.
      Furthermore, the omentum harbored a stable frequency of viral genome-positive
      cells through early and into long-term latency, while removal of the omentum
      prior to infection resulted in a slight decrease in the establishment of splenic
      latency following intraperitoneal infection. These data provide the first
      evidence that the omentum is a site of chronic MHV68 infection that may
      contribute to the maintenance of chronic infection.

PMID- 22952646
TI  - Exocrine pancreatic carcinogenesis and autotaxin expression.
AB  - Exocrine pancreatic cancer is an aggressive disease with an exceptionally high
      mortality rate. Genetic analysis suggests a causative role for environmental
      factors, but consistent epidemiological support is scarce and no biomarkers for
      monitoring the effects of chemical pancreatic carcinogens are available. With the
      objective to identify common traits for chemicals inducing pancreatic tumors we
      studied the National Toxicology Program (NTP) bioassay database. We found that
      male rats were affected more often than female rats and identified eight
      chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis
      generating process we used a text mining tool to analyse published literature for
      suggested mode of actions (MOA). The resulting MOA analysis suggested
      inflammatory responses as common feature. In cell studies we found that all the
      chemicals increased protein levels of the inflammatory protein autotaxin (ATX) in
      Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive
      migration were also frequent effects, consistent with ATX activation.
      Testosterone has previously been implicated in pancreatic carcinogenesis and we
      found that it increased ATX levels. Our data show that ATX is a target for
      chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate
      ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms
      of action may include stimulated invasive growth and metastasis. ATX may interact
      with hormones or onco- or suppressor-genes often deregulated in exocrine
      pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting
      pancreatic tumor development.

PMID- 22952647
TI  - Ruler arrays reveal haploid genomic structural variation.
AB  - Despite the known relevance of genomic structural variants to pathogen behavior,
      cancer, development, and evolution, certain repeat based structural variants may
      evade detection by existing high-throughput techniques. Here, we present ruler
      arrays, a technique to detect genomic structural variants including insertions
      and deletions (indels), duplications, and translocations. A ruler array exploits
      DNA polymerase's processivity to detect physical distances between defined
      genomic sequences regardless of the intervening sequence. The method combines a
      sample preparation protocol, tiling genomic microarrays, and a new computational
      analysis. The analysis of ruler array data from two genomic samples enables the
      identification of structural variation between the samples. In an empirical test
      between two closely related haploid strains of yeast ruler arrays detected 78% of
      the structural variants larger than 100 bp.

PMID- 22952648
TI  - TFAP2B influences the effect of dietary fat on weight loss under energy
      restriction.
AB  - BACKGROUND: Numerous gene loci are related to single measures of body weight and
      shape. We investigated if 55 SNPs previously associated with BMI or waist
      measures, modify the effects of fat intake on weight loss and waist reduction
      under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of
      771 obese adults. ( REGISTRATION: ISRCTN25867281.) One SNP was selected for
      replication in another weight loss intervention study of 934 obese adults. The
      original trial was a 10-week 600 kcal/d energy-deficient diet with energy
      percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used
      an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for
      estimation of interaction effects. The main outcomes were intervention weight
      loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in
      the low/high-fat groups. In the replication study, it was -23/-12 among those
      reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was
      associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and
      GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat
      (interaction p-value; p = 0.00007). The replication study showed a similar (non
      significant) interaction pattern. Waist reduction results generally were similar.
      Study-strengths include (i) the discovery study randomised trial design combined
      with the replication opportunity (ii) the strict dietary intake control in both
      studies (iii) the large sample sizes of both studies. Limitations are (i) the low
      minor allele frequency of the TFAP2B polymorphism, making it hard to investigate
      non-additive genetic effects (ii) the different interventions preventing
      identical replication-discovery study designs (iii) some missing data for non
      completers and dietary intake. No adverse effects/outcomes or side-effects were
      observed. CONCLUSIONS: Under energy restriction, TFAP2B may modify the effect of
      dietary fat intake on weight loss and waist reduction.

PMID- 22952649
TI  - Does pet ownership in infancy lead to asthma or allergy at school age? Pooled
      analysis of individual participant data from 11 European birth cohorts.
AB  - OBJECTIVE: To examine the associations between pet keeping in early childhood and
      asthma and allergies in children aged 6-10 years. DESIGN: Pooled analysis of
      individual participant data of 11 prospective European birth cohorts that
      recruited a total of over 22,000 children in the 1990s.  EXPOSURE DEFINITION:
      Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the
      first 2 years of life.  OUTCOME DEFINITION: Current asthma (primary outcome),
      allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years
      of age. DATA SYNTHESIS: Three-step approach: (i) Common definition of outcome and
      exposure variables across cohorts; (ii) calculation of adjusted effect estimates
      for each cohort; (iii) pooling of effect estimates by using random effects meta
      analysis models. RESULTS: We found no association between furry and feathered pet
      keeping early in life and asthma in school age. For example, the odds ratio for
      asthma comparing cat ownership with "no pets" (10 studies, 11489 participants)
      was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds
      ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433
      participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s)
      and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84)
      (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis
      we did not find associations regarding any type of pet ownership early in life.
      However, we found some evidence for an association between ownership of furry
      pets during the first 2 years of life and reduced likelihood of becoming
      sensitized to aero-allergens. CONCLUSIONS: Pet ownership in early life did not
      appear to either increase or reduce the risk of asthma or allergic rhinitis
      symptoms in children aged 6-10. Advice from health care practitioners to avoid or
      to specifically acquire pets for primary prevention of asthma or allergic
      rhinitis in children should not be given.

PMID- 22952650
TI  - Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain
      perception.
AB  - BACKGROUND: Serotonin (5-HT) is highly involved in pain regulation and serotonin
      1A (5-HT1A) receptors are important in determining central 5-HT tone.
      Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to
      inter-individual differences in human pain sensitivity. The minor G-allele of the
      HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of
      serotonergic neurons and reduces postsynaptic expression of the receptor.
      Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite
      directions at mild compared to high noxious intensities. Based upon this and
      several other similar observations, we hypothesized that G-carriers would exhibit
      a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at
      higher noxious intensities. METHODS: Fourty-nine healthy individuals were
      selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed
      along with VAS-ratings of a range of suprathreshold noxious heat intensities (45
      degrees C-49 degrees C). Nociceptive-flexion reflex (NFR) thresholds were also
      assessed. RESULTS: Volunteers did not deviate significantly from Hardy-Weinberg
      equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This
      relative hypoalgesia was abolished at suprathreshold noxious intensities where G
      carriers instead increased their ratings of heat-pain significantly more than C
      homozygotes. No differences with regard to NFR-thresholds emerged.
      CONCLUSION/SIGNIFICANCE: To the best of our knowledge this is the first study of
      human pain perception on the basis of variation in HTR1A. The results illustrate
      the importance of including a range of stimulus intensities in assessments of
      pain sensitivity. In speculation, we propose that an attenuated serotonergic tone
      may be related to a 'hypo- to hyperalgesic' response-pattern. The involved
      mechanisms could be of clinical interest as variation in pain regulation is known
      to influence the risk of developing pain pathologies. Further investigations are
      therefore warranted.

PMID- 22952651
TI  - Prevalence of pulmonary tuberculosis--a baseline survey in central India.
AB  - BACKGROUND: The present study provides an estimate of the prevalence of
      bacteriologially positive pulmonary tuberculosis in Jabalpur, a district in
      central India. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional
      survey was undertaken in Jabalpur District of the central Indian state of Madhya
      Pradesh. A stratified cluster sampling design was adopted to select the sample.
      All eligible individuals were questioned for pulmonary symptoms suggestive of TB
      disease. Two sputum samples were collected from all eligible individuals and were
      examined by Ziehl-Neelsen smear microscopy and solid media culture methods. Of
      the 99,918 individuals eligible for screening, 95,071 (95.1%) individuals were
      screened. Of these, 7,916 (8.3%) were found to have symptoms and sputum was
      collected from 7,533 (95.2%) individuals. Overall prevalence of bacteriologically
      positive PTB was found to be 255.3 per 100,000 population (95% C.I: 195.3-315.4).
      Prevalence was significantly higher (p<0.001) amongst males (355.8; 95% C.I:
      304.4-413.4) compared with females (109.0; 95% C.I: 81.2-143.3). Prevalence was
      also significantly higher in rural areas (348.9; 95% C.I: 292.6-412.8) as
      compared to the urban (153.9; 95% C.I: 123.2-190.1). CONCLUSIONS/SIGNIFICANCE:
      The TB situation in Jabalpur district, central India, is observed to be
      comparable to the TB situation at the national level (255.3 versus 249). There is
      however, a need to maintain and further strengthen TB control measures on a
      sustained and long term basis in the area to have a significant impact on the
      disease prevalence in the community.

PMID- 22952652
TI  - A mechanical model of cell segregation driven by differential adhesion.
AB  - From simulations that begin with a random mix of two cell types, we monitor
      progress towards segregation driven by contact-mediated linkage of model cells,
      which is equivalent to the cell-cell adhesion of real cells. In comparison with
      real cell experiments, we show that this mechanical model can account for the
      observed extent of segregation obtained by differential adhesion in a 2D cell
      culture assay of cells with differentially expressed cadherin molecules.
      Calibration of virtual to real time allowed us to estimate a time course for
      these experiments that was within 50% agreement for the simulations compared to
      differential adhesion of cells. In contrast, simulations of differential adhesion
      do not account for the rate of segregation driven by interactions between EphB2
      receptor and ephrinB1 expressing cells which occurs an order of magnitude faster.
      The latter result suggests that mechanisms additional or alternative to
      differential adhesion contribute to Eph-ephrin mediated cell segregation.

PMID- 22952654
TI  - Identification of novel targets for miR-29a using miRNA proteomics.
AB  - MicroRNAs (miRNAs) are short regulatory RNA molecules that interfere with the
      expression of target mRNA by binding to complementary sequences. Currently, the
      most common method for identification of targets of miRNAs is computational
      prediction based on free energy change calculations, target site accessibility
      and conservation. Such algorithms predict hundreds of targets for each miRNA,
      necessitating tedious experimentation to identify the few functional targets.
      Here we explore the utility of miRNA-proteomics as an approach to identifying
      functional miRNA targets. We used Stable Isotope Labeling by amino acids in cell
      culture (SILAC) based proteomics to detect differences in protein expression
      induced by the over-expression of miR-34a and miR-29a. Over-expression of miR
      29a, a miRNA expressed in the brain and in cells of the blood lineage, resulted
      in the differential expression of a set of proteins. Gene Ontology based
      classification showed that a significant sub-set of these targets, including
      Voltage Dependent Anion Channel 1 and 2 (VDAC1 and VDAC2) and ATP synthetase,
      were mitochondrial proteins involved in apoptosis. Using reporter assays, we
      established that miR-29a targets the 3' Untranslated Regions (3' UTR) of VDAC1
      and VDAC2. However, due to the limited number of proteins identified using this
      approach and the inability to differentiate between primary and secondary effects
      we conclude that miRNA-proteomics is of limited utility as a high-throughput
      alternative for sensitive and unbiased miRNA target identification. However, this
      approach was valuable for rapid assessment of the impact of the miRNAs on the
      cellular proteome and its biological role in apoptosis.

PMID- 22952655
TI  - The limits of mean-field heterozygosity estimates under spatial extension in
      simulated plant populations.
AB  - Computational models of evolutionary processes are increasingly required to
      incorporate multiple and diverse sources of data. A popular feature to include in
      population genetics models is spatial extension, which reflects more accurately
      natural populations than does a mean field approach. However, such models
      necessarily violate the mean field assumptions of classical population genetics,
      as do natural populations in the real world. Recently, it has been questioned
      whether classical approaches are truly applicable to the real world. Individual
      based models (IBM) are a powerful and versatile approach to achieve integration
      in models. In this study an IBM was used to examine how populations of plants
      deviate from classical expectations under spatial extension. Populations of
      plants that used three different mating strategies were placed in a range of
      arena sizes giving crowded to sparse occupation densities. Using a measure of
      population density, the pollen communication distance (P(cd)), the deviation
      exhibited by outbreeding populations differed from classical mean field
      expectations by less than 5% when P(cd) was less than 1, and over this threshold
      value the deviation significantly increased. Populations with an intermediate
      mating strategy did not have such a threshold and deviated directly with
      increasing isolation between individuals. Populations with a selfing strategy
      were influenced more by the mating strategy than by increased isolation. In all
      cases pollen dispersal was more influential than seed dispersal. The IBM model
      showed that mean field calculations can be reasonably applied to natural
      outbreeding plant populations that occur at a density in which individuals are
      less than the average pollen dispersal distance from their neighbors.

PMID- 22952653
TI  - Vitamin K-antagonists accelerate atherosclerotic calcification and induce a
      vulnerable plaque phenotype.
AB  - BACKGROUND: Vitamin K-antagonists (VKA) are treatment of choice and standard care
      for patients with venous thrombosis and thromboembolic risk. In experimental
      animal models as well as humans, VKA have been shown to promote medial
      elastocalcinosis. As vascular calcification is considered an independent risk
      factor for plaque instability, we here investigated the effect of VKA on coronary
      calcification in patients and on calcification of atherosclerotic plaques in the
      ApoE(-/-) model of atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: A total of
      266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non
      VKA users) underwent 64-slice MDCT to assess the degree of coronary artery
      disease (CAD). VKA-users developed significantly more calcified coronary plaques
      as compared to non-VKA users. ApoE(-/-) mice (10 weeks) received a Western type
      diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with
      vitamin K(1) (VK(1), 1.5 mg/g) or vitamin K(1) and warfarin (VK(1)&W; 1.5 mg/g &
      3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin
      significantly increased frequency and extent of vascular calcification. Also,
      plaque calcification comprised microcalcification of the intimal layer.
      Furthermore, warfarin treatment decreased plaque expression of calcification
      regulatory protein carboxylated matrix Gla-protein, increased apoptosis and,
      surprisingly outward plaque remodeling, without affecting overall plaque burden.
      CONCLUSIONS/SIGNIFICANCE: VKA use is associated with coronary artery plaque
      calcification in patients with suspected CAD and causes changes in plaque
      morphology with features of plaque vulnerability in ApoE(-/-) mice. Our findings
      underscore the need for alternative anticoagulants that do not interfere with the
      vitamin K cycle.

PMID- 22952656
TI  - Differential effects of two fermentable carbohydrates on central appetite
      regulation and body composition.
AB  - BACKGROUND: Obesity is rising at an alarming rate globally. Different fermentable
      carbohydrates have been shown to reduce obesity. The aim of the present study was
      to investigate if two different fermentable carbohydrates (inulin and beta
      glucan) exert similar effects on body composition and central appetite regulation
      in high fat fed mice. METHODOLOGY/PRINCIPAL FINDINGS: Thirty six C57BL/6 male
      mice were randomized and maintained for 8 weeks on a high fat diet containing 0%
      (w/w) fermentable carbohydrate, 10% (w/w) inulin or 10% (w/w) beta-glucan
      individually. Fecal and cecal microbial changes were measured using fluorescent
      in situ hybridization, fecal metabolic profiling was obtained by proton nuclear
      magnetic resonance ((1)H NMR), colonic short chain fatty acids were measured by
      gas chromatography, body composition and hypothalamic neuronal activation were
      measured using magnetic resonance imaging (MRI) and manganese enhanced MRI
      (MEMRI), respectively, PYY (peptide YY) concentration was determined by
      radioimmunoassay, adipocyte cell size and number were also measured. Both inulin
      and beta-glucan fed groups revealed significantly lower cumulative body weight
      gain compared with high fat controls. Energy intake was significantly lower in
      beta-glucan than inulin fed mice, with the latter having the greatest effect on
      total adipose tissue content. Both groups also showed an increase in the numbers
      of Bifidobacterium and Lactobacillus-Enterococcus in cecal contents as well as
      feces. beta-Glucan appeared to have marked effects on suppressing MEMRI
      associated neuronal signals in the arcuate nucleus, ventromedial hypothalamus,
      paraventricular nucleus, periventricular nucleus and the nucleus of the tractus
      solitarius, suggesting a satiated state. CONCLUSIONS/SIGNIFICANCE: Although both
      fermentable carbohydrates are protective against increased body weight gain, the
      lower body fat content induced by inulin may be metabolically advantageous. beta
      Glucan appears to suppress neuronal activity in the hypothalamic appetite
      centers. Differential effects of fermentable carbohydrates open new possibilities
      for nutritionally targeting appetite regulation and body composition.

PMID- 22952657
TI  - Mesenchymal stem cells in inflammation microenvironment accelerates
      hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal
      transition.
AB  - In response to inflammation, mesenchymal stem cells (MSCs) are known to migrate
      to tissue injury sites to participate in immune modulation, tissue remodeling and
      wound healing. Tumors apply persistent mechanical and pathological stress to
      tissues and causes continual infiltration of MSCs. Here, we demonstrate that MSCs
      promote human hepatocellular carcinoma (HCC) metastasis under the influence of
      inflammation. The metastasis promoting effect could be imitated with the
      supernatant of MSCs pretreated with IFNgamma and TNFalpha. Interestingly,
      treatment of HCC cells with the supernatant leads to epithelial-mesenchymal
      transition (EMT), an effect related to the production of TGFbeta by cytokines
      stimulated MSCs. Importantly, the levels of MSCs expressing SSEA4 in clinical HCC
      samples significantly correlated with poor prognosis of HCC, and EMT of HCC was
      strongly associated with a shorter cancer-free interval (CFI) and a worse overall
      survival (OS). Therefore, our results suggest that MSCs in tumor inflammatory
      microenvironment could promote tumor metastasis through TGFbeta-induced EMT.

PMID- 22952659
TI  - CytoKavosh: a cytoscape plug-in for finding network motifs in large biological
      networks.
AB  - Network motifs are small connected sub-graphs that have recently gathered much
      attention to discover structural behaviors of large and complex networks. Finding
      motifs with any size is one of the most important problems in complex and large
      networks. It needs fast and reliable algorithms and tools for achieving this
      purpose. CytoKavosh is one of the best choices for finding motifs with any given
      size in any complex network. It relies on a fast algorithm, Kavosh, which makes
      it faster than other existing tools. Kavosh algorithm applies some well known
      algorithmic features and includes tricky aspects, which make it an efficient
      algorithm in this field. CytoKavosh is a Cytoscape plug-in which supports us in
      finding motifs of given size in a network that is formerly loaded into the
      Cytoscape work-space (directed or undirected). High performance of CytoKavosh is
      achieved by dynamically linking highly optimized functions of Kavosh's C++ to the
      Cytoscape Java program, which makes this plug-in suitable for analyzing large
      biological networks. Some significant attributes of CytoKavosh is efficiency in
      time usage and memory and having no limitation related to the implementation in
      motif size. CytoKavosh is implemented in a visual environment Cytoscape that is
      convenient for the users to interact and create visual options to analyze the
      structural behavior of a network. This plug-in can work on any given network and
      is very simple to use and generates graphical results of discovered motifs with
      any required details. There is no specific Cytoscape plug-in, specific for
      finding the network motifs, based on original concept. So, we have introduced for
      the first time, CytoKavosh as the first plug-in, and we hope that this plug-in
      can be improved to cover other options to make it the best motif-analyzing tool.

PMID- 22952658
TI  - AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced
      heart failure.
AB  - BACKGROUND: Histidine-rich calcium binding protein (HRC) is located in the lumen
      of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA
      affecting Ca(2+) cycling in the SR. Chronic overexpression of HRC that may
      disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac
      hypertrophy. Ablation of HRC showed relatively normal phenotypes under basal
      condition, but exhibited a significantly increased susceptibility to
      isoproterenol-induced cardiac hypertrophy. In the present study, we characterized
      the functions of HRC related to Ca(2+) cycling and pathogenesis of cardiac
      hypertrophy using the in vitro siRNA- and the in vivo adeno-associated virus
      (AAV)-mediated HRC knock-down (KD) systems, respectively. METHODOLOGY/PRINCIPAL
      FINDINGS: AAV-mediated HRC-KD system was used with or without C57BL/6 mouse model
      of transverse aortic constriction-induced failing heart (TAC-FH) to examine
      whether HRC-KD could enhance cardiac function in failing heart (FH). Initially we
      expected that HRC-KD could elicit cardiac functional recovery in failing heart
      (FH), since predesigned siRNA-mediated HRC-KD enhanced Ca(2+) cycling and
      increased activities of RyR2 and SERCA2 without change in SR Ca(2+) load in
      neonatal rat ventricular cells (NRVCs) and HL-1 cells. However, AAV9-mediated HRC
      KD in TAC-FH was associated with decreased fractional shortening and increased
      cardiac fibrosis compared with control. We found that phospho-RyR2, phospho
      CaMKII, phospho-p38 MAPK, and phospho-PLB were significantly upregulated by HRC
      KD in TAC-FH. A significantly increased level of cleaved caspase-3, a cardiac
      cell death marker was also found, consistent with the result of TUNEL assay.
      CONCLUSIONS/SIGNIFICANCE: Increased Ca(2+) leak and cytosolic Ca(2+)
      concentration due to a partial KD of HRC could enhance activity of CaMKII and
      phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in
      TAC-FH. Our results present evidence that down-regulation of HRC could
      deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca(2+)
      cycling.

PMID- 22952660
TI  - Itga2b regulation at the onset of definitive hematopoiesis and commitment to
      differentiation.
AB  - Product of the Itga2b gene, CD41 contributes to hematopoietic stem cell (HSC) and
      megakaryocyte/platelet functions. CD41 expression marks the onset of definitive
      hematopoiesis in the embryo where it participates in regulating the numbers of
      multipotential progenitors. Key to platelet aggregation, CD41 expression also
      characterises their precursor, the megakaryocyte, and is specifically up
      regulated during megakaryopoiesis. Though phenotypically unique, megakaryocytes
      and HSC share numerous features, including key transcription factors, which could
      indicate common sub-regulatory networks. In these respects, Itga2b can serve as a
      paradigm to study features of both developmental-stage and HSC- versus
      megakaryocyte-specific regulations. By comparing different cellular contexts, we
      highlight a mechanism by which internal promoters participate in Itga2b
      regulation. A developmental process connects epigenetic regulation and promoter
      switching leading to CD41 expression in HSC. Interestingly, a similar process can
      be observed at the Mpl locus, which codes for another receptor that defines both
      HSC and megakaryocyte identities. Our study shows that Itga2b expression is
      controlled by lineage-specific networks and associates with H4K8ac in
      megakaryocyte or H3K27me3 in the multipotential hematopoietic cell line HPC7.
      Correlating with the decrease in H3K27me3 at the Itga2b Iocus, we find that
      following commitment to megakaryocyte differentiation, the H3K27 demethylase
      Jmjd3 up-regulation influences both Itga2b and Mpl expression.

PMID- 22952661
TI  - Transmission of a 2009 H1N1 pandemic influenza virus occurs before fever is
      detected, in the ferret model.
AB  - During the early phase of the 2009 influenza pandemic, attempts were made to
      contain the spread of the virus. Success of reactive control measures may be
      compromised if the proportion of transmission that occurs before overt clinical
      symptoms develop is high. In this study we investigated the timing of
      transmission of an early prototypic strain of pandemic H1N1 2009 influenza virus
      in the ferret model. Ferrets are the only animal model in which this can be
      assessed because they display typical influenza-like clinical signs including
      fever and sneezing after infection. We assessed transmission from infected
      animals to sentinels that were placed either in direct contact or in adjacent
      cages, the latter reflecting the respiratory droplet (RD) transmission route. We
      found that pre-symptomatic influenza transmission occurred via both contact and
      respiratory droplet exposure before the earliest clinical sign, fever, developed.
      Three of 3 animals exposed in direct contact between day 1 and 2 after infection
      of the donor animals became infected, and 2/3 of the animals exposed at this time
      period by the RD route acquired the infection, with the third animal becoming
      seropositive indicating either a low level infection or significant exposure.
      Moreover, this efficient transmission did not temporally correlate with
      respiratory symptoms, such as coughs and sneezes, but rather with the peak viral
      titre in the nose. Indeed respiratory droplet transmission did not occur late in
      infection, even though this was when sneezing and coughing were most apparent.
      None of the 3 animals exposed at this time by the RD route became infected and
      these animals remained seronegative at the end of the experiment. These data have
      important implications for pandemic planning strategies and suggest that
      successful containment is highly unlikely for a human-adapted influenza virus
      that transmits efficiently within a population.

PMID- 22952662
TI  - TARGETgene: a tool for identification of potential therapeutic targets in cancer.
AB  - The vast array of in silico resources and data of high throughput profiling
      currently available in life sciences research offer the possibility of aiding
      cancer gene and drug discovery process. Here we propose to take advantage of
      these resources to develop a tool, TARGETgene, for efficiently identifying
      mutation drivers, possible therapeutic targets, and drug candidates in cancer.
      The simple graphical user interface enables rapid, intuitive mapping and analysis
      at the systems level. Users can find, select, and explore identified target genes
      and compounds of interest (e.g., novel cancer genes and their enriched biological
      processes), and validate predictions using user-defined benchmark genes (e.g.,
      target genes detected in RNAi screens) and curated cancer genes via TARGETgene.
      The high-level capabilities of TARGETgene are also demonstrated through two
      applications in this paper. The predictions in these two applications were then
      satisfactorily validated by several ways, including known cancer genes, results
      of RNAi screens, gene function annotations, and target genes of drugs that have
      been used or in clinical trial in cancer treatments. TARGETgene is freely
      available from the Biomedical Simulations Resource web site
      (http://bmsr.usc.edu/Software/TARGET/TARGET.html).

PMID- 22952663
TI  - Plant-derived phenolics inhibit the accrual of structurally characterised protein
      and lipid oxidative modifications.
AB  - Epidemiological data suggest that plant-derived phenolics beneficial effects
      include an inhibition of LDL oxidation. After applying a screening method based
      on 2,4-dinitrophenyl hydrazine-protein carbonyl reaction to 21 different plant
      derived phenolic acids, we selected the most antioxidant ones. Their effect was
      assessed in 5 different oxidation systems, as well as in other model proteins.
      Mass-spectrometry was then used, evidencing a heterogeneous effect on the
      accumulation of the structurally characterized protein carbonyl glutamic and
      aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL
      apoprotein. After TOF based lipidomics, we identified the most abundant
      differential lipids in Cu(++)-incubated LDL as 1-palmitoyllysophosphatidylcholine
      and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds
      prevented the accumulation of those phospholipids and the cellular impairment
      induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated
      the effect of the intake of a phenolic-enriched extract in plasma protein and
      lipid modifications in a well-established model of atherosclerosis (diet-induced
      hypercholesterolemia in hamsters). This showed that a dietary supplement with a
      phenolic-enriched extract diminished plasma protein oxidative and lipid damage.
      Globally, these data show structural basis of antioxidant properties of plant
      derived phenolic acids in protein oxidation that may be relevant for the health
      promoting effects of its dietary intake.

PMID- 22952664
TI  - Toll-like receptor 7 stimulates the expression of Epstein-Barr virus latent
      membrane protein 1.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Toll-like receptor 7
      (TLR7) is involved in host innate immunity against pathogens, and its aberrant
      activation is linked to the development of systemic lupus erythematosus (SLE,
      also called "lupus"). Type I interferons (IFN) are apparently driving forces for
      lupus pathogenesis. Previously, we found that EBV latent membrane protein 1
      (LMP1) primes cells for IFN production. In this report, the relationship among
      EBV LMP1, TLRs, and IFN production are examined. We find that TLR7 activation
      increases the expression of EBV LMP1, and IFN regulatory factor 7 (IRF7) is
      involved in the stimulation process. TLR7 activation did not induce IFNs from EBV
      infected cells, but potentiates those cells for IFN production by TLR3 or TLR9
      activation. In addition, we find that LMP1 and IFNs are co-expressed in the same
      cells in some lupus patients. Therefore, the aberrant activation of TLR7 might
      induce LMP1 expression and LMP1-expression cells may be producing IFNs in lupus
      patients. These results suggest EBV might be an exacerbating factor in some lupus
      patients via promoting IFN production.

PMID- 22952665
TI  - Development of quinoxaline 1, 4-dioxides resistance in Escherichia coli and
      molecular change under resistance selection.
AB  - Quinoxaline 1, 4-dioxides (QdNOs) has been used in animals as antimicrobial
      agents and growth promoters for decades. However, the resistance to QdNOs in
      pathogenic bacteria raises worldwide concern but it is barely known. To explore
      the molecular mechanism involved in development of QdNOs resistance in
      Escherichia coli, 6 strains selected by QdNOs in vitro and 21 strains isolated
      from QdNOs-used swine farm were subjected to MIC determination and PCR
      amplification of oqxA gene. A conjugative transfer was carried out to evaluate
      the transfer risk of QdNOs resistant determinant. Furthermore, the
      transcriptional profile of a QdNOs-resistant E. coli (79O4-2) selected in vitro
      with its parent strain 79-161 was assayed with a prokaryotic suppression
      subtractive hybridization (SSH) PCR cDNA subtraction. The result showed that more
      than 95% (20/21) clinical isolates were oqxA positive, while all the 6 induced
      QdNOs-resistant strains carried no oqxA gene and exhibited low frequency of
      conjugation. 44 fragments were identified by SSH PCR subtraction in the QdNOs
      resistant strain 79O4-2. 18 cDNAs were involved in biosynthesis of Fe-S cluster
      (narH), protein (rpoA, trmD, truA, glyS, ileS, rplFCX, rpsH, fusA), lipoate
      (lipA), lipid A (lpxC), trehalose (otsA), CTP(pyrG) and others molecular. The 11
      cDNAs were related to metabolism or degradation of glycolysis (gpmA and pgi) and
      proteins (clpX, clpA, pepN and fkpB). The atpADG and ubiB genes were associated
      with ATP biosynthesis and electron transport chain. The pathway of the functional
      genes revealed that E. coli may adapt the stress generated by QdNOs or develop
      specific QdNOs-resistance by activation of antioxidative agents biosynthesis
      (lipoate and trehalose), protein biosynthesis, glycolysis and oxidative
      phosphorylation. This study initially reveals the possible molecular mechanism
      involved in the development of QdNOs-resistance in E. coli, providing with novel
      insights in prediction and assessment of the emergency and horizontal transfer of
      QdNOs-resistance in E. coli.

PMID- 22952666
TI  - Characterization of TLX expression in neural stem cells and progenitor cells in
      adult brains.
AB  - TLX has been shown to play an important role in regulating the self-renewal and
      proliferation of neural stem cells in adult brains. However, the cellular
      distribution of endogenous TLX protein in adult brains remains to be elucidated.
      In this study, we used immunostaining with a TLX-specific antibody to show that
      TLX is expressed in both neural stem cells and transit-amplifying neural
      progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then,
      using a double thymidine analog labeling approach, we showed that almost all of
      the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX
      positive cells in the SVZ represented the thymidine analog-negative, relatively
      quiescent neural stem cell population. Using cell type markers and short-term
      BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly
      dividing type C cells. Furthermore, loss of TLX expression dramatically reduced
      BrdU label-retaining neural stem cells and the actively dividing neural
      progenitor cells in the SVZ, but substantially increased GFAP staining and
      extended GFAP processes. These results suggest that TLX is essential to maintain
      the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the
      SVZ lose neural stem cell property upon loss of TLX expression. Understanding the
      cellular distribution of TLX and its function in specific cell types may provide
      insights into the development of therapeutic tools for neurodegenerative diseases
      by targeting TLX in neural stem/progenitors cells.

PMID- 22952667
TI  - Influenza A virus does not encode a tetherin antagonist with Vpu-like activity
      and induces IFN-dependent tetherin expression in infected cells.
AB  - The interferon-induced host cell factor tetherin inhibits release of human
      immunodeficiency virus (HIV) from the plasma membrane of infected cells and is
      counteracted by the HIV-1 protein Vpu. Influenza A virus (FLUAV) also buds from
      the plasma membrane and is not inhibited by tetherin. Here, we investigated if
      FLUAV encodes a functional equivalent of Vpu for tetherin antagonism. We found
      that expression of the FLUAV protein NS1, which antagonizes the interferon (IFN)
      response, did not block the tetherin-mediated restriction of HIV release, which
      was rescued by Vpu. Similarly, tetherin-mediated inhibition of HIV release was
      not rescued by FLUAV infection. In contrast, FLUAV infection induced tetherin
      expression on target cells in an IFN-dependent manner. These results suggest that
      FLUAV escapes the antiviral effects of tetherin without encoding a tetherin
      antagonist with Vpu-like activity.

PMID- 22952668
TI  - Interferon gamma and sonic hedgehog signaling are required to dysregulate murine
      neural stem/precursor cells.
AB  - BACKGROUND: The pro-inflammatory cytokine interferon gamma (IFNgamma), a key
      player in various neurological diseases, was recently shown to induce a
      dysregulated phenotype in neural stem/precursor cells (NSPCs) that is
      characterized by the simultaneous expression of glial and neuronal markers and
      irregular electrophysiological properties. Thus far, the mechanisms of this
      phenomenon have remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: To determine if
      binding of the signal transducers and activators of transcription (Stat 1) to the
      sonic hedgehog (SHH) promoter is important for this phenomenon to occur,
      chromatin immunoprecipitation and pharmacological inhibition studies were
      performed. We report here that the activation of both the Stat 1 and SHH pathways
      is necessary to elicit the dysregulated phenotype. CONCLUSIONS/SIGNIFICANCE:
      Thus, blocking these pathways might preserve functional differentiation of NSPCs
      under inflammatory conditions leading to more effective regeneration.

PMID- 22952669
TI  - Extraordinary sex ratios: cultural effects on ecological consequences.
AB  - We model sex-structured population dynamics to analyze pairwise competition
      between groups differing both genetically and culturally. A sex-ratio allele is
      expressed in the heterogametic sex only, so that assumptions of Fisher's analysis
      do not apply. Sex-ratio evolution drives cultural evolution of a group-associated
      trait governing mortality in the homogametic sex. The two-sex dynamics under
      resource limitation induces a strong Allee effect that depends on both sex ratio
      and cultural trait values. We describe the resulting threshold, separating
      extinction from positive growth, as a function of female and male densities. When
      initial conditions avoid extinction due to the Allee effect, different sex ratios
      cannot coexist; in our model, greater female allocation always invades and
      excludes a lesser allocation. But the culturally transmitted trait interacts with
      the sex ratio to determine the ecological consequences of successful invasion.
      The invading female allocation may permit population persistence at self
      regulated equilibrium. For this case, the resident culture may be excluded, or
      may coexist with the invader culture. That is, a single sex-ratio allele in
      females and a cultural dimorphism in male mortality can persist; a low-mortality
      resident trait is maintained by father-to-son cultural transmission. Otherwise,
      the successfully invading female allocation excludes the resident allele and
      culture and then drives the population to extinction via a shortage of males.
      Finally, we show that the results obtained under homogeneous mixing hold, with
      caveats, in a spatially explicit model with local mating and diffusive dispersal
      in both sexes.

PMID- 22952670
TI  - Multiple infection and microdiversity among Helicobacter pylori isolates in a
      single host in India.
AB  - Helicobacter pylori is one of the most diverse bacterial species that chronically
      infects more than 70% of Indian population. Interestingly, data showing
      microdiversity of the H. pylori strains within a particular gastric niche
      remained scarce. To understand the extent of genetic diversity among H. pylori
      strains within a given host, 30 patients with gastro-duodenal problems were
      subjected to endoscopy and from each patient 10 single colonies were isolated.
      Characterization of each of these 10 single colonies by DNA fingerprinting as
      well as genotyping of several important genetic markers viz. cagA, vacA, iceA,
      vapD, cag PAI empty site, IS605, RFLP and two other genetic segments within cag
      PAI revealed that all of the 30 patients were infected with more than one strain
      and sometimes strains with 5 to 6 types of genetic variants. Analyses of certain
      genetic loci showed the microdiversity among the colonies from single patient,
      which may be due to the recombination events during long-term carriage of the
      pathogen. These results suggest that most of the patients have acquired H. pylori
      due to repeated exposure to this pathogen with different genetic make-up, which
      may increase the possibility of super infections. Genetic exchanges between these
      unrelated H. pylori strains may support certain H. pylori variant to grow better
      in a given host than the parental strain and thereby increasing the possibility
      for the severity of the infection.

PMID- 22952671
TI  - Nitrogen addition regulates soil nematode community composition through ammonium
      suppression.
AB  - Nitrogen (N) enrichment resulting from anthropogenic activities has greatly
      changed the composition and functioning of soil communities. Nematodes are one of
      the most abundant and diverse groups of soil organisms, and they occupy key
      trophic positions in the soil detritus food web. Nematodes have therefore been
      proposed as useful indicators for shifts in soil ecosystem functioning under N
      enrichment. Here, we monitored temporal dynamics of the soil nematode community
      using a multi-level N addition experiment in an Inner Mongolia grassland.
      Measurements were made three years after the start of the experiment. We used
      structural equation modeling (SEM) to explore the mechanisms regulating nematode
      responses to N enrichment. Across the N enrichment gradient, significant
      reductions in total nematode abundance, diversity (H' and taxonomic richness),
      maturity index (MI), and the abundance of root herbivores, fungivores and
      omnivores-predators were found in August. Root herbivores recovered in September,
      contributing to the temporal variation of total nematode abundance across the N
      gradient. Bacterivores showed a hump-shaped relationship with N addition rate,
      both in August and September. Ammonium concentration was negatively correlated
      with the abundance of total and herbivorous nematodes in August, but not in
      September. Ammonium suppression explained 61% of the variation in nematode
      richness and 43% of the variation in nematode trophic group composition. Ammonium
      toxicity may occur when herbivorous nematodes feed on root fluid, providing a
      possible explanation for the negative relationship between herbivorous nematodes
      and ammonium concentration in August. We found a significantly positive
      relationship between fungivores and fungal phospholipid fatty acids (PLFA),
      suggesting bottom-up control of fungivores. No such relationship was found
      between bacterivorous nematodes and bacterial PLFA. Our findings contribute to
      the understanding of effects of N enrichment in semiarid grassland on soil
      nematode trophic groups, and the cascading effects in the detrital soil food web.

PMID- 22952672
TI  - MRKAd5 HIV-1 Gag/Pol/Nef vaccine-induced T-cell responses inadequately predict
      distance of breakthrough HIV-1 sequences to the vaccine or viral load.
AB  - BACKGROUND: The sieve analysis for the Step trial found evidence that
      breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were
      more divergent from the vaccine insert than placebo sequences in regions with
      predicted epitopes. We linked the viral sequence data with immune response and
      acute viral load data to explore mechanisms for and consequences of the observed
      sieve effect. METHODS: Ninety-one male participants (37 placebo and 54 vaccine
      recipients) were included; viral sequences were obtained at the time of HIV-1
      diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at
      the first or second week post-diagnosis. Acute viral load was obtained at RNA
      positive and antibody-negative visits. FINDINGS: Vaccine recipients had a greater
      magnitude of post-infection CD8+ T cell response than placebo recipients (median
      1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median
      4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more
      divergent from the insert than placebo sequences in regions of Nef targeted by
      pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude
      and breadth of pre-infection responses did not correlate with distance of the
      viral sequence to the insert (p>0.50). Acute log viral load trended lower in
      vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference
      was not significant (p = 0.27). Neither was acute viral load associated with
      distance of the viral sequence to the insert (p>0.30). INTERPRETATION: Despite
      evidence of anamnestic responses, the sieve effect was not well explained by
      available measures of T-cell immunogenicity. Sequence divergence from the vaccine
      was not significantly associated with acute viral load. While point estimates
      suggested weak vaccine suppression of viral load, the result was not significant
      and more viral load data would be needed to detect suppression.

PMID- 22952673
TI  - CYP1A1 Ile462Val polymorphism contributes to lung cancer susceptibility among
      lung squamous carcinoma and smokers: a meta-analysis.
AB  - Many studies have examined the association between the CYP1A1 Ile462Val gene
      polymorphisms and lung cancer risk in various populations, but their results have
      been inconsistent. To assess this relationship more precisely, a meta-analysis
      was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects
      were included. A significantly elevated lung cancer risk was associated with 2
      Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08
      1.40; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.23) in
      overall population. In the stratified analysis, a significant association was
      found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC.
      Additionally, a significant association was found in smoker population and not
      found in non-smoker populations. This meta-analysis suggests that the Ile462Val
      polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in
      Asian and Caucasian populations and there is an interaction with smoking status,
      but these associations vary in different histological types of lung caner.

PMID- 22952674
TI  - Hypoxia-inducible factor-1alpha regulates chemotactic migration of pancreatic
      ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene.
AB  - CX3CR1 is an important chemokine receptor and regulates the chemotactic migration
      of pancreatic ductal adenocarcinoma (PDAC) cells. Up to now, its regulatory
      mechanism remains largely undefined. Here, we report that hypoxia upregulates the
      expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor
      (HIF)-1alpha expression was knocked down in vitro and in vivo, the expression of
      CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay
      demonstrated that HIF-1alpha bound to the hypoxia-response element (HRE; 5'
      A/GCGTG-3') of CX3CR1 promoter under normoxia, and this binding was significantly
      enhanced under hypoxia. Overexpression of HIF-1alpha significantly upregulated
      the expression of luciferase reporter gene under the control of the CX3CR1
      promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1alpha
      may regulate cancer cell migration through CX3CR1. The HIF-1alpha/CX3CR1 pathway
      might represent a valuable therapeutic target to prevent invasion and distant
      metastasis in PDAC.

PMID- 22952675
TI  - Genome-scale reconstruction and analysis of the metabolic network in the
      hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - We describe the reconstruction of a genome-scale metabolic model of the
      crenarchaeon Sulfolobus solfataricus, a hyperthermoacidophilic microorganism. It
      grows in terrestrial volcanic hot springs with growth occurring at pH 2-4
      (optimum 3.5) and a temperature of 75-80 degrees C (optimum 80 degrees C). The
      genome of Sulfolobus solfataricus P2 contains 2,992,245 bp on a single circular
      chromosome and encodes 2,977 proteins and a number of RNAs. The network comprises
      718 metabolic and 58 transport/exchange reactions and 705 unique metabolites,
      based on the annotated genome and available biochemical data. Using the model in
      conjunction with constraint-based methods, we simulated the metabolic fluxes
      induced by different environmental and genetic conditions. The predictions were
      compared to experimental measurements and phenotypes of S. solfataricus.
      Furthermore, the performance of the network for 35 different carbon sources known
      for S. solfataricus from the literature was simulated. Comparing the growth on
      different carbon sources revealed that glycerol is the carbon source with the
      highest biomass flux per imported carbon atom (75% higher than glucose).
      Experimental data was also used to fit the model to phenotypic observations. In
      addition to the commonly known heterotrophic growth of S. solfataricus, the
      crenarchaeon is also able to grow autotrophically using the hydroxypropionate
      hydroxybutyrate cycle for bicarbonate fixation. We integrated this pathway into
      our model and compared bicarbonate fixation with growth on glucose as sole carbon
      source. Finally, we tested the robustness of the metabolism with respect to gene
      deletions using the method of Minimization of Metabolic Adjustment (MOMA), which
      predicted that 18% of all possible single gene deletions would be lethal for the
      organism.

PMID- 22952676
TI  - Fenton reaction induced cancer in wild type rats recapitulates genomic
      alterations observed in human cancer.
AB  - Iron overload has been associated with carcinogenesis in humans. Intraperitoneal
      administration of ferric nitrilotriacetate initiates a Fenton reaction in renal
      proximal tubules of rodents that ultimately leads to a high incidence of renal
      cell carcinoma (RCC) after repeated treatments. We performed high-resolution
      microarray comparative genomic hybridization to identify characteristics in the
      genomic profiles of this oxidative stress-induced rat RCCs. The results revealed
      extensive large-scale genomic alterations with a preference for deletions.
      Deletions and amplifications were numerous and sometimes fragmented,
      demonstrating that a Fenton reaction is a cause of such genomic alterations in
      vivo. Frequency plotting indicated that two of the most commonly altered loci
      corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were
      proportionally associated with Met expression and/or amplification, and
      clustering analysis confirmed our results. Furthermore, we developed a procedure
      to compare whole genomic patterns of the copy number alterations among different
      species based on chromosomal syntenic relationship. Patterns of the rat RCCs
      showed the strongest similarity to the human RCCs among five types of human
      cancers, followed by human malignant mesothelioma, an iron overload-associated
      cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale
      genomic alterations during carcinogenesis, which may result in distinct genomic
      profiles. Based on the characteristics of extensive genome alterations in human
      cancer, our results suggest that this chemical reaction may play a major role
      during human carcinogenesis.

PMID- 22952677
TI  - Three dimensional assessment of the pharyngeal airway in individuals with non
      syndromic cleft lip and palate.
AB  - INTRODUCTION: Children with cleft lip and palate (CLP) are known to have airway
      problems. Previous studies have shown that individuals with CLP have a 30%
      reduction in nasal airway size compared to non-cleft controls. No reports have
      been found on cross-sectional area and volume of the pharyngeal airway in clefts.
      Introduction of Cone-Beam CT (CBCT) and imaging software has facilitated
      generation of 3D images for assessment of the cross-sectional area and volume of
      the airway. OBJECTIVE: To assess the pharyngeal airway in individuals with CLP
      using CBCT by measuring volume and smallest cross-sectional areas and compare
      with 19 age- and sex-matched non-cleft controls. METHODS: Retrospective study of
      CBCT data of pre-adolescent individuals (N = 19, Mean age = 10.6, 7 females, 12
      males, UCLP = 6, BCLP = 3) from the Center for Craniofacial Anomalies. Volumetric
      analysis was performed using image segmentation features in CB Works 3.0. Volume
      and smallest cross-sectional were studied in both groups. Seven measurements were
      repeated to verify reliability using Pearson correlation coefficient. Volume and
      cross-sectional area differences were analyzed using paired t-tests. RESULTS: The
      method was found to be reliable. Individuals with CLP did not exhibit smaller
      total airway volume and cross sectional area than non-CLP controls. CONCLUSION:
      3D imaging using CBCT and CB Works is reliable for assessing airway volume.
      Previous studies have shown that the nasal airway is restricted in individuals
      with CLP. In our study, we found that the pharyngeal airway is not compromised in
      these individuals.

PMID- 22952678
TI  - Toxoplasma gondii infection induces suppression in a mouse model of allergic
      airway inflammation.
AB  - Allergic asthma is an inflammatory disorder characterized by infiltration of the
      airway wall with inflammatory cells driven mostly by activation of Th2
      lymphocytes, eosinophils and mast cells. There is a link between increased
      allergy and a reduction of some infections in Western countries. Epidemiological
      data also show that respiratory allergy is less frequent in people exposed to
      orofecal and foodborne microbes such as Toxoplasma gondii. We previously showed
      that both acute and chronic parasite T. gondii infection substantially blocked
      development of airway inflammation in adult BALB/c mice. Based on the high levels
      of IFN-gamma along with the reduction of Th2 phenotype, we hypothesized that the
      protective effect might be related to the strong Th1 immune response elicited
      against the parasite. However, other mechanisms could also be implicated. The
      possibility that regulatory T cells inhibit allergic diseases has received
      growing support from both animal and human studies. Here we investigated the
      cellular mechanisms involved in T. gondii induced protection against allergy. Our
      results show for the first time that thoracic lymph node cells from mice
      sensitized during chronic T. gondii infection have suppressor activity.
      Suppression was detected both in vitro, on allergen specific T cell proliferation
      and in vivo, on allergic lung inflammation after adoptive transference from
      infected/sensitized mice to previously sensitized animals. This ability was found
      to be contact-independent and correlated with high levels of TGF-beta and
      CD4(+)FoxP3(+) cells.

PMID- 22952679
TI  - Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial
      localization of tyrosine kinase Src and tyrosine phosphatase SHP2.
AB  - Our previous research demonstrated that sepsis produces mitochondrial dysfunction
      with increased mitochondrial oxidative stress in the heart. The present study
      investigated the role of mitochondria-localized signaling molecules, tyrosine
      kinase Src and tyrosine phosphatase SHP2, in sepsis-induced cardiac mitochondrial
      dysfunction using a rat pneumonia-related sepsis model. SD rats were given an
      intratracheal injection of Streptococcus pneumoniae, 4*10(6) CFU per rat, (or
      vehicle for shams); heart tissues were then harvested and subcellular fractions
      were prepared. By Western blot, we detected a gradual and significant decrease in
      Src and an increase in SHP2 in cardiac mitochondria within 24 hours post
      inoculation. Furthermore, at 24 hours post-inoculation, sepsis caused a near 70%
      reduction in tyrosine phosphorylation of all cardiac mitochondrial proteins.
      Decreased tyrosine phosphorylation of certain mitochondrial structural proteins
      (porin, cyclophilin D and cytochrome C) and functional proteins (complex II
      subunit 30kD and complex I subunit NDUFB8) were evident in the hearts of septic
      rats. In vitro, pre-treatment of mitochondrial fractions with recombinant active
      Src kinase elevated OXPHOS complex I and II-III activity, whereas the effect of
      SHP2 phosphatase was opposite. Neither Src nor SHP2 affected complex IV and V
      activity under the same conditions. By immunoprecipitation, we showed that Src
      and SHP2 consistently interacted with complex I and III in the heart, suggesting
      that complex I and III contain putative substrates of Src and SHP2. In addition,
      in vitro treatment of mitochondrial fractions with active Src suppressed sepsis
      associated mtROS production and protected aconitase activity, an indirect marker
      of mitochondrial oxidative stress. On the contrary, active SHP2 phosphatase
      overproduced mtROS and deactivated aconitase under the same in vitro conditions.
      In conclusion, our data suggest that changes in mitochondria-localized signaling
      molecules Src and SHP2 constitute a potential signaling pathway to affect
      mitochondrial dysfunction in the heart during sepsis.

PMID- 22952680
TI  - Rv2190c, an NlpC/P60 family protein, is required for full virulence of
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB) possesses at
      least five genes predicted to encode proteins with NlpC/P60 hydrolase domains,
      including the relatively uncharacterized Rv2190c. As NlpC/P60 domain-containing
      proteins are associated with diverse roles in bacterial physiology, our objective
      was to characterize Rv2190c in M. tuberculosis growth and virulence. Our data
      indicate that lack of Rv2190c is associated with impaired growth, both in vitro
      and during an in vivo mouse model of TB. These growth defects are associated with
      altered colony morphology and phthiocerol dimycocerosate levels, indicating that
      Rv2190c is involved in cell wall maintenance and composition. In addition, we
      have demonstrated that Rv2190c is expressed during active growth phase and that
      its protein product is immunogenic during infection. Our findings have
      significant implications, both for better understanding the role of Rv2190c in M.
      tuberculosis biology and also for translational developments.

PMID- 22952681
TI  - Transcriptome and proteome dynamics of a light-dark synchronized bacterial cell
      cycle.
AB  - BACKGROUND: Growth of the ocean's most abundant primary producer, the
      cyanobacterium Prochlorococcus, is tightly synchronized to the natural 24-hour
      light-dark cycle. We sought to quantify the relationship between transcriptome
      and proteome dynamics that underlie this obligate photoautotroph's highly
      choreographed response to the daily oscillation in energy supply.
      METHODOLOGY/PRINCIPAL FINDINGS: Using RNA-sequencing transcriptomics and mass
      spectrometry-based quantitative proteomics, we measured timecourses of paired
      mRNA-protein abundances for 312 genes every 2 hours over a light-dark cycle.
      These temporal expression patterns reveal strong oscillations in transcript
      abundance that are broadly damped at the protein level, with mRNA levels varying
      on average 2.3 times more than the corresponding protein. The single strongest
      observed protein-level oscillation is in a ribonucleotide reductase, which may
      reflect a defense strategy against phage infection. The peak in abundance of most
      proteins also lags that of their transcript by 2-8 hours, and the two are
      completely antiphase for some genes. While abundant antisense RNA was detected,
      it apparently does not account for the observed divergences between expression
      levels. The redirection of flux through central carbon metabolism from daytime
      carbon fixation to nighttime respiration is associated with quite small changes
      in relative enzyme abundances. CONCLUSIONS/SIGNIFICANCE: Our results indicate
      that expression responses to periodic stimuli that are common in natural
      ecosystems (such as the diel cycle) can diverge significantly between the mRNA
      and protein levels. Protein expression patterns that are distinct from those of
      cognate mRNA have implications for the interpretation of transcriptome and
      metatranscriptome data in terms of cellular metabolism and its biogeochemical
      impact.

PMID- 22952682
TI  - Activity-based labeling of matrix metalloproteinases in living vertebrate
      embryos.
AB  - Extracellular matrix (ECM) remodeling is a physiologically and developmentally
      essential process mediated by a family of zinc-dependent extracellular proteases
      called matrix metalloproteinases (MMPs). In addition to complex transcriptional
      control, MMPs are subject to extensive post-translational regulation. Because of
      this, classical biochemical, molecular and histological techniques that detect
      the expression of specific gene products provide useful but limited data
      regarding the biologically relevant activity of MMPs. Using benzophenone-bearing
      hydroxamate-based probes that interact with the catalytic zinc ion in MMPs,
      active proteases can be covalently 'tagged' by UV cross-linking. This approach
      has been successfully used to tag MMP-2 in vitro in tissue culture supernatants,
      and we show here that this probe tags proteins with mobilities consistent with
      known MMPs and detectable gelatinolytic activity in homogenates of zebrafish
      embryos. Furthermore, because of the transparency of the zebrafish embryo, UV
      photocroslinking can be accomplished in vivo, and rhodamated benzophenone probe
      is detected in striking spatial patterns consistent with known distributions of
      active matrix remodeling in embryos. Finally, in metamorphosing Xenopus tadpoles,
      this probe can be used to biotinylate active MMP-2 by injecting it and cross
      linking it in vivo, allowing the protein to be subsequently extracted and
      biochemically identified.

PMID- 22952683
TI  - miRNA regulation of gene expression: a predictive bioinformatics analysis in the
      postnatally developing monkey hippocampus.
AB  - Regulation of gene expression in the postnatally developing hippocampus might
      contribute to the emergence of selective memory function. However, the mechanisms
      that underlie the co-regulation of expression of hundreds of genes in different
      cell types at specific ages in distinct hippocampal regions have yet to be
      elucidated. By performing genome-wide microarray analyses of gene expression in
      distinct regions of the monkey hippocampal formation during early postnatal
      development, we identified one particular group of genes exhibiting a down
      regulation of expression, between birth and six months of age in CA1 and after
      one year of age in CA3, to reach expression levels observed at 6-12 years of age.
      Bioinformatics analyses using NCBI, miRBase, TargetScan, microRNA.org and
      Affymetrix tools identified a number of miRNAs capable of regulating the
      expression of these genes simultaneously in different cell types, i.e., in
      neurons, astrocytes and oligodendrocytes. Interestingly, sixty-five percent of
      these miRNAs are conserved across species, from rodents to humans; whereas thirty
      five percent are specific to primates, including humans. In addition, we found
      that some genes exhibiting greater down-regulation of their expression were the
      predicted targets of a greater number of these miRNAs. In sum, miRNAs may play a
      fundamental role in the co-regulation of gene expression in different cell types.
      This mechanism is partially conserved across species, and may thus contribute to
      the similarity of basic hippocampal characteristics across mammals. This
      mechanism also exhibits a phylogenetic diversity that may contribute to more
      subtle species differences in hippocampal structure and function observed at the
      cellular level.

PMID- 22952684
TI  - Transcriptome analysis of Nicotiana tabacum infected by Cucumber mosaic virus
      during systemic symptom development.
AB  - Virus infection of plants may induce a variety of disease symptoms. However,
      little is known about the molecular mechanism of systemic symptom development in
      infected plants. Here we performed the first next-generation sequencing study to
      identify gene expression changes associated with disease development in tobacco
      plants (Nicotiana tabacum cv. Xanthi nc) induced by infection with the M strain
      of Cucumber mosaic virus (M-CMV). Analysis of the tobacco transcriptome by RNA
      Seq identified 95,916 unigenes, 34,408 of which were new transcripts by database
      searches. Deep sequencing was subsequently used to compare the digital gene
      expression (DGE) profiles of the healthy plants with the infected plants at six
      sequential disease development stages, including vein clearing, mosaic, severe
      chlorosis, partial and complete recovery, and secondary mosaic. Thousands of
      differentially expressed genes were identified, and KEGG pathway analysis of
      these genes suggested that many biological processes, such as photosynthesis,
      pigment metabolism and plant-pathogen interaction, were involved in systemic
      symptom development. Our systematic analysis provides comprehensive
      transcriptomic information regarding systemic symptom development in virus
      infected plants. This information will help further our understanding of the
      detailed mechanisms of plant responses to viral infection.

PMID- 22952685
TI  - Deep sequencing and microarray hybridization identify conserved and species
      specific microRNAs during somatic embryogenesis in hybrid yellow poplar.
AB  - BACKGROUND: To date, several studies have indicated a major role for microRNAs
      (miRNAs) in regulating plant development, but miRNA-mediated regulation of the
      developing somatic embryo is poorly understood, especially during early stages of
      somatic embryogenesis in hardwood plants. In this study, Solexa sequencing and
      miRNA microfluidic chips were used to discover conserved and species-specific
      miRNAs during somatic embryogenesis of hybrid yellow poplar (Liriodendron
      tulipifera*L. chinense). METHODOLOGY/PRINCIPAL FINDINGS: A total of 17,214,153
      reads representing 7,421,623 distinct sequences were obtained from a short RNA
      library generated from small RNAs extracted from all stages of somatic embryos.
      Through a combination of deep sequencing and bioinformatic analyses, we
      discovered 83 sequences with perfect matches to known miRNAs from 33 conserved
      miRNA families and 273 species-specific candidate miRNAs. MicroRNA microarray
      results demonstrated that many conserved and species-specific miRNAs were
      expressed in hybrid yellow poplar embryos. In addition, the microarray also
      detected another 149 potential miRNAs, belonging to 29 conserved families, which
      were not discovered by deep sequencing analysis. The biological processes and
      molecular functions of the targets of these miRNAs were predicted by carrying out
      BLAST search against Arabidopsis thaliana GenBank sequences and then analyzing
      the results with Gene Ontology. CONCLUSIONS: Solexa sequencing and microarray
      hybridization were used to discover 232 candidate conserved miRNAs from 61 miRNA
      families and 273 candidate species-specific miRNAs in hybrid yellow poplar. In
      these predicted miRNAs, 64 conserved miRNAs and 177 species-specific miRNAs were
      detected by both sequencing and microarray hybridization. Our results suggest
      that miRNAs have wide-ranging characteristics and important roles during all
      stages of somatic embryogenesis in this economically important species.

PMID- 22952686
TI  - Biochemical characterization of highly purified leucine-rich repeat kinases 1 and
      2 demonstrates formation of homodimers.
AB  - Leucine-rich repeat kinase 1 and 2 (LRRK1 and LRRK2) are large multidomain
      proteins containing kinase, GTPase and multiple protein-protein interaction
      domains, but only mutations in LRRK2 are linked to familial Parkinson's disease
      (PD). Independent studies suggest that LRRK2 exists in the cell as a complex
      compatible with the size of a dimer. However, whether this complex is truly a
      homodimer or a heterologous complex formed by monomeric LRRK2 with other proteins
      has not been definitively proven due to the limitations in obtaining highly pure
      proteins suitable for structural characterization. Here, we used stable
      expression of LRRK1 and LRRK2 in HEK293T cell lines to produce recombinant LRRK1
      and LRRK2 proteins of greater than 90% purity. Both purified LRRKs are folded,
      with a predominantly alpha-helical secondary structure and are capable of binding
      GTP with similar affinity. Furthermore, recombinant LRRK2 exhibits robust
      autophosphorylation activity, phosphorylation of model peptides in vitro and ATP
      binding. In contrast, LRRK1 does not display significant autophosphorylation
      activity and fails to phosphorylate LRRK2 model substrates, although it does bind
      ATP. Using these biochemically validated proteins, we show that LRRK1 and LRRK2
      are capable of forming homodimers as shown by single-particle transmission
      electron microscopy and immunogold labeling. These LRRK dimers display an
      elongated conformation with a mean particle size of 145 A and 175 A respectively,
      which is disrupted by addition of 6M guanidinium chloride. Immunogold staining
      revealed double-labeled particles also in the pathological LRRK2 mutant G2019S
      and artificial mutants disrupting GTPase and kinase activities, suggesting that
      point mutations do not hinder the dimeric conformation. Overall, our findings
      indicate for the first time that purified and active LRRK1 and LRRK2 can form
      dimers in their full-length conformation.

PMID- 22952687
TI  - Proteomic research reveals the stress response and detoxification of yeast to
      combined inhibitors.
AB  - The tolerant mechanism of yeast to the combination of three inhibitors (furfural,
      phenol and acetic acid) was investigated using 2-DE combined with MALDI-TOF/TOF
      MS. The stress response and detoxification related proteins (e.g., Ahp1p, Hsp26p)
      were expressed higher in the tolerant yeast than in the parental yeast. The
      expressions of most nitrogen metabolism related proteins (e.g. Gdh1p, Met1p) were
      higher in the parental yeast, indicating that the tolerant yeast decreases its
      nitrogen metabolism rate to reserve energy, and possesses high resistance to the
      stress of combined inhibitors. Furthermore, upon exposure to the inhibitors, the
      proteins related to protein folding, degradation and translation (e.g., Ssc1p,
      Ubp14p, Efb1p) were all significantly affected, and the oxidative stress related
      proteins (e.g., Ahp1p, Grx1p) were increased. Knockdown of genes related to the
      oxidative stress and unfolded protein response (Grx1, Gre2, Asc1) significantly
      decreased the tolerance of yeast to inhibitors, which further suggested that
      yeast responded to the inhibitors mainly by inducing unfolded protein response.
      This study reveals that increasing the detoxification and tolerating oxidative
      stress, and/or decreasing the nitrogen metabolism would be promising strategies
      in developing more tolerant strains to the multiple inhibitors in lignocellulose
      hydrolysates.

PMID- 22952688
TI  - Immobilization of lipases on alkyl silane modified magnetic nanoparticles: effect
      of alkyl chain length on enzyme activity.
AB  - BACKGROUND: Biocatalytic processes often require a full recycling of biocatalysts
      to optimize economic benefits and minimize waste disposal. Immobilization of
      biocatalysts onto particulate carriers has been widely explored as an option to
      meet these requirements. However, surface properties often affect the amount of
      biocatalysts immobilized, their bioactivity and stability, hampering their wide
      applications. The aim of this work is to explore how immobilization of lipases
      onto magnetite nanoparticles affects their biocatalytic performance under
      carefully controlled surface modification. METHODOLOGY/PRINCIPAL FINDINGS:
      Magnetite nanoparticles, prepared through a co-precipitation method, were coated
      with alkyl silanes of different alkyl chain lengths to modulate their surface
      hydrophobicity. Candida rugosa lipase was then directly immobilized onto the
      modified nanoparticles through hydrophobic interaction. Enzyme activity was
      assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of
      immobilized lipases was found to increase with increasing chain length of the
      alkyl silane. Furthermore, the catalytic activities of lipases immobilized on
      trimethoxyl octadecyl silane (C18) modified Fe(3)O(4) were a factor of 2 or more
      than the values reported from other surface immobilized systems. After 7
      recycles, the activities of the lipases immobilized on C18 modified nanoparticles
      retained 65%, indicating significant enhancement of stability as well through
      hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated
      easy separation and recycling with high activity retaining.
      CONCLUSIONS/SIGNIFICANCE: The activity of immobilized lipases increased with
      increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface
      modification of magnetite nanoparticles. Lipase stability was also improved
      through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles
      are thus highly attractive carriers for enzyme immobilization enabling efficient
      enzyme recovery and recycling.

PMID- 22952689
TI  - Small mammal investigation in spotted fever focus with DNA-barcoding and
      taxonomic implications on rodents species from Hainan of China.
AB  - Although mammals are a well-studied group of animals, making accurate field
      identification of small mammals is still complex because of morphological
      variation across developmental stages, color variation of pelages, and often
      damaged osteological and dental characteristics. In 2008, small mammals were
      collected for an epidemiological study of a spotted fever outbreak in Hainan,
      China. Ten species of small mammals were identified by morphological characters
      in the field, most using pelage color characters only. The study is extended
      here, in order to assess whether DNA barcoding would be suitable as an
      identification tool in these small mammals. Barcode clusters showed some
      incongruence with morphospecies, especially for some species of Rattus and
      Niviventer, so molecular delineation was carried out with an expanded dataset of
      combined cytochrome b (Cyt-b) and cytochrome c oxidase subunit I (COI) sequences.
      COI sequences were successfully amplified from 83% of collected mammals, but
      failed in all specimens of Suncus murinus, which were thus excluded in DNA
      barcoding analysis. Of note, ten molecular taxonomic units were found from
      samples of nine morphologically identified species. Accordingly, 11 species of
      small mammals were present in the investigated areas, including four Rattus
      species, three Niviventer species, Callosciurus erythraeus, Neohylomys
      hainanensis, Tupaia belangeri, and Suncus murinus. Based on the results of the
      phylogenetic and molecular delineation analyses, the systematic status of some
      rodent species should be redefined. R. rattus hainanicus and R. rattus sladeni
      are synonyms of R. andamanensis. R. losea from China and Southeast Asia comprises
      two independent species: R. losea and R. sakeratensis. Finally, the taxonomic
      status of three putative species of Niviventer should be further confirmed
      according to morphological, molecular and ecological characters.

PMID- 22952690
TI  - Pathological changes in the white matter after spinal contusion injury in the
      rat.
AB  - It has been shown previously that after spinal cord injury, the loss of grey
      matter is relatively faster than loss of white matter suggesting interventions to
      save white matter tracts offer better therapeutic possibilities. Loss of white
      matter in and around the injury site is believed to be the main underlying cause
      for the subsequent loss of neurological functions. In this study we used a series
      of techniques, including estimations of the number of axons with pathology,
      immunohistochemistry and mapping of distribution of pathological axons, to better
      understand the temporal and spatial pathological events in white matter following
      contusion injury to the rat spinal cord. There was an initial rapid loss of axons
      with no detectable further loss beyond 1 week after injury. Immunoreactivity for
      CNPase indicated that changes to oligodendrocytes are rapid, extending to several
      millimetres away from injury site and preceding much of the axonal loss, giving
      early prediction of the final volume of white matter that survived. It seems that
      in juvenile rats the myelination of axons in white matter tracts continues for
      some time, which has an important bearing on interpretation of our, and previous,
      studies. The amount of myelin debris and axon pathology progressively decreased
      with time but could still be observed at 10 weeks after injury, especially at
      more distant rostral and caudal levels from the injury site. This study provides
      new methods to assess injuries to spinal cord and indicates that early
      interventions are needed for the successful sparing of white matter tracts
      following injury.

PMID- 22952691
TI  - Effects of Internet-based guided self-help problem-solving therapy for
      adolescents with depression and anxiety: a randomized controlled trial.
AB  - BACKGROUND: Symptoms of depression and anxiety are highly prevalent in
      adolescence and they are the cause of considerable suffering. Even so,
      adolescents are not inclined to seek professional help for emotional problems.
      Internet-based preventive interventions have been suggested as a feasible method
      of providing appropriate care to adolescents with internalizing symptoms. The
      objective of this study was to evaluate the effects of preventive Internet-based
      (guided) self-help problem-solving therapy (PST) for adolescents reporting mild
      to moderate symptoms of depression and/or anxiety as compared to a waiting list
      control group (WL). METHODOLOGY/PRINCIPAL FINDINGS: A total of 45 participants
      were randomized to the 2 conditions. PST consisted of 5 weekly lessons.
      Participants were supported by e-mail. Self-report measures of depression and
      anxiety were filled in at baseline and after 3 weeks, 5 weeks, and 4 months. Of
      the 45 participants, 28 (62.2%) completed questionnaires after 3 weeks, 28
      (62.2%) after 5 weeks, and 27 (60%) after 4 months. Hierarchical linear modeling
      analyses revealed overall improvement over time for both groups on depressive and
      anxiety symptoms. However, no significant group x time interactions were found.
      No differences were found between completers and non-completers.
      CONCLUSIONS/SIGNIFICANCE: Results show that depressive and anxiety symptoms
      declined in both groups. No support was found, however, for the assumption that
      Internet-based PST was efficacious in reducing depression and anxiety in
      comparison to the waiting list control group. This finding could represent lack
      of power. TRIAL REGISTRATION: Netherlands Trial Register NTR1322.

PMID- 22952692
TI  - Sex allocation in California oaks: trade-offs or resource tracking?
AB  - Trade-offs in sex resource allocation are commonly inferred from a negative
      correlation between male and female reproduction. We found that for three
      California oak species, aboveground annual net productivity (ANP) differences
      among individuals were primarily correlated with water availability and soil
      fertility. Reproductive biomass increased with ANP, but the relative allocation
      to reproduction was constant, indicating that reproduction tracked productivity,
      which in turn tracked site quality. Although there was a negative correlation
      between male and female reproduction, this was not the result of a resource
      investment trade-off, but rather a byproduct of the positive correlation between
      female reproductive biomass and ANP combined with the greater overall resource
      allocation to female, compared to male, function. Thus, we reject the hypothesis
      of a trade-off between these key life-history components within individuals of
      these species. For long-lived individuals, a plastic resource tracking response
      to environmental fluctuations may be more adaptive than directly linking life
      history traits through trade-offs.

PMID- 22952693
TI  - Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane
      partners.
AB  - Cathepsin S (catS), which is expressed in normal human keratinocytes and
      localized close to the dermal-epidermal junction (DEJ) degrades some of major
      basement membrane (BM) constituents. Among them, catS readily hydrolyzed in a
      time and dose dependent manner human nidogen-1 (nid-1) and nidogen-2, which are
      key proteins in the BM structure. CatS preferentially cleaved nid-1 at both acid
      and neutral pH. Hydrolysis of nid-1 was hampered in murine ctss(-/-) spleen
      lysates pretreated with inhibitors of other classes of proteases. Nid-1 was
      cleaved within its G2 and G3 globular domains that are both involved in
      interactions with other BM components. Binding assays with soluble and
      immobilized ligands indicated that catS altered the formation of complexes
      between nid-1 and other BM components. Assuming that the cleavage of nid-1
      impairs its ability to crosslink with BM partners and perturbs the viscoelastic
      properties of BM matrix, these data indicate that catS may participate in BM
      proteolysis, in addition to already identified proteases.

PMID- 22952694
TI  - A case-control study estimating accident risk for alcohol, medicines and illegal
      drugs.
AB  - BACKGROUND: The aim of the present study was to assess the risk of having a
      traffic accident after using alcohol, single drugs, or a combination, and to
      determine the concentrations at which this risk is significantly increased.
      METHODS: A population-based case-control study was carried out, collecting whole
      blood samples of both cases and controls, in which a number of drugs were
      detected. The risk of having an accident when under the influence of drugs was
      estimated using logistic regression adjusting for gender, age and time period of
      accident (cases)/sampling (controls). The main outcome measures were odds ratio
      (OR) for accident risk associated with single and multiple drug use. In total,
      337 cases (negative: 176; positive: 161) and 2726 controls (negative: 2425;
      positive: 301) were included in the study. RESULTS: Main findings were that 1)
      alcohol in general (all the concentrations together) caused an elevated crash
      risk; 2) cannabis in general also caused an increase in accident risk; at a cut
      off of 2 ng/mL THC the risk of having an accident was four times the risk
      associated with the lowest THC concentrations; 3) when ranking the adjusted OR
      from lowest to highest risk, alcohol alone or in combination with other drugs was
      related to a very elevated crash risk, with the highest risk for stimulants
      combined with sedatives. CONCLUSION: The study demonstrated a concentration
      dependent crash risk for THC positive drivers. Alcohol and alcohol-drug
      combinations are by far the most prevalent substances in drivers and subsequently
      pose the largest risk in traffic, both in terms of risk and scope.

PMID- 22952695
TI  - Low-dose strontium-90 irradiation is effective in preventing the recurrence of
      pterygia: a ten-year study.
AB  - BACKGROUND: To study the long-term effects of low-dosage strontium-90 (Sr90)
      irradiation on the recurrence of pterygium. METHODOLOGY/PRINCIPAL FINDINGS: One
      hundred twenty eyes from 104 patients with primary or recurrent pterygia were
      treated with surgery followed by Sr90 irradiation. In brief, starting on the
      sixth day after surgery, patients were treated with irradiation three times every
      other day at a total combined dosage of 2000 cGy to 3000 cGy. Corneal topography
      was used to evaluate ocular surface regularity before and after treatment.
      Patient follow-up was performed 2 days, 5 days, 2 weeks, 1 month, 3 months, 1
      year, 5 years, and 10 years after surgery. Recurrence of pterygium was not
      observed in any of the patients in this study. Obvious cataract progression was
      observed in 6 eyes, which may be due to aging. During follow-up studies, only one
      eye was reported with dryness and foreign-body sensation. Significant pterygium
      induced astigmatism was observed in corneal topography, which decreased after
      surgery. CONCLUSIONS/SIGNIFICANCE: Sr90 irradiation is effective in preventing
      the recurrence of primary and recurrent pterygia. We recommend delivering a total
      combined dosage of 2000 cGy to 3000 cGy of Sr90 irradiation administered in three
      batches every other day starting from the sixth day after surgery. Surgery is
      important in the rapid recovery of the cornea from pterygium-induced astigmatism.

PMID- 22952696
TI  - Overexpression of Thellungiella halophila H+-pyrophosphatase gene improves low
      phosphate tolerance in maize.
AB  - Low phosphate availability is a major constraint on plant growth and agricultural
      productivity. Engineering a crop with enhanced low phosphate tolerance by
      transgenic technique could be one way of alleviating agricultural losses due to
      phosphate deficiency. In this study, we reported that transgenic maize plants
      that overexpressed the Thellungiella halophila vacuolar H(+)-pyrophosphatase gene
      (TsVP) were more tolerant to phosphate deficit stress than the wild type. Under
      phosphate sufficient conditions, transgenic plants showed more vigorous root
      growth than the wild type. When phosphate deficit stress was imposed, they also
      developed more robust root systems than the wild type, this advantage facilitated
      phosphate uptake, which meant that transgenic plants accumulated more phosphorus.
      So the growth and development in the transgenic maize plants were not damaged as
      much as in the wild type plants under phosphate limitation. Overexpression of
      TsVP increased the expression of genes involved in auxin transport, which
      indicated that the development of larger root systems in transgenic plants might
      be due in part to enhanced auxin transport which controls developmental events in
      plants. Moreover, transgenic plants showed less reproductive development
      retardation and a higher grain yield per plant than the wild type plants when
      grown in a low phosphate soil. The phenotypes of transgenic maize plants
      suggested that the overexpression of TsVP led to larger root systems that allowed
      transgenic maize plants to take up more phosphate, which led to less injury and
      better performance than the wild type under phosphate deficiency conditions. This
      study describes a feasible strategy for improving low phosphate tolerance in
      maize and reducing agricultural losses caused by phosphate deficit stress.

PMID- 22952697
TI  - Analyses of the redistribution of work following cardiac resynchronisation
      therapy in a patient specific model.
AB  - Regulation of regional work is essential for efficient cardiac function. In
      patients with heart failure and electrical dysfunction such as left branch bundle
      block regional work is often depressed in the septum. Following cardiac
      resynchronisation therapy (CRT) this heterogeneous distribution of work can be
      rebalanced by altering the pattern of electrical activation. To investigate the
      changes in regional work in these patients and the mechanisms underpinning the
      improved function following CRT we have developed a personalised computational
      model. Simulations of electromechanical cardiac function in the model estimate
      the regional stress, strain and work pre- and post-CRT. These simulations predict
      that the increase in observed work performed by the septum following CRT is not
      due to an increase in the volume of myocardial tissue recruited during
      contraction but rather that the volume of recruited myocardium remains the same
      and the average peak work rate per unit volume increases. These increases in the
      peak average rate of work is is attributed to slower and more effective
      contraction in the septum, as opposed to a change in active tension. Model
      results predict that this improved septal work rate following CRT is a result of
      resistance to septal contraction provided by the LV free wall. This resistance
      results in septal shortening over a longer period which, in turn, allows the
      septum to contract while generating higher levels of active tension to produce a
      higher work rate.

PMID- 22952698
TI  - Prenatal exposure to bereavement and type-2 diabetes: a Danish longitudinal
      population based study.
AB  - BACKGROUND: The etiology of type-2 diabetes is only partly known, and a possible
      role of prenatal stress in programming offspring for insulin resistance has been
      suggested by animal models. Previously, we found an association between prenatal
      stress and type-1 diabetes. Here we examine the association between prenatal
      exposure to maternal bereavement during preconception and pregnancy and
      development of type-2 diabetes in the off-spring. METHODS: We utilized data from
      the Danish Civil Registration System to identify singleton births in Denmark born
      January 1(st) 1979 through December 31(st) 2008 (N = 1,878,246), and linked them
      to their parents, grandparents, and siblings. We categorized children as exposed
      to bereavement during prenatal life if their mothers lost an elder child, husband
      or parent during the period from one year before conception to the child's birth.
      We identified 45,302 children exposed to maternal bereavement; the remaining
      children were included in the unexposed cohort. The outcome of interest was
      diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from
      birth using log-linear poisson regression models and used person-years as the
      offset variable. All models were adjusted for maternal residence, income,
      education, marital status, sibling order, calendar year, sex, and parents'
      history of diabetes at the time of pregnancy. RESULTS: We found children exposed
      to bereavement during their prenatal life were more likely to have a type-2
      diabetes diagnosis later in life (aIRR: 1.31, 1.01-1.69). These findings were
      most pronounced when bereavement was caused by death of an elder child (aIRR:
      1.51, 0.94-2.44). Results also indicated the second trimester of pregnancy to be
      the most sensitive period of bereavement exposure (aIRR:2.08, 1.15-3.76).
      CONCLUSIONS: Our data suggests that fetal exposure to maternal bereavement during
      preconception and the prenatal period may increase the risk for developing type-2
      diabetes in childhood and young adulthood.

PMID- 22952699
TI  - Serum carcinoembryonic antigen is associated with abdominal visceral fat
      accumulation in female Korean nonsmokers.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is a tumor marker overexpressed in
      adenocarcinoma that has proinflammatory properties. Recent studies have reported
      that CEA is positively associated with carotid atherosclerosis and metabolic
      syndrome. Because visceral obesity is a known risk factor for cardiometabolic
      diseases, CEA may also be associated with visceral adiposity. Therefore, we
      investigated the relationship between serum CEA concentration and visceral
      obesity in female Korean nonsmokers. METHODS: A total of 270 Korean female
      nonsmokers were enrolled during their routine health check-ups. Biomarkers of
      metabolic risk factors were assessed along with body composition by computed
      tomography. Serum CEA levels were measured by using a chemiluminescence
      immunoassay analyzer. RESULTS: Serum CEA levels correlated with visceral fat
      area, fasting glucose, and triglyceride levels after adjusting for age and BMI.
      The mean visceral fat area increased significantly with the increasing CEA
      tirtiles. In a step-wise multiple regression analysis, age (beta = 0.26, p<0.01)
      and visceral fat area (beta = 0.19, p = 0.03) were identified as explanatory
      variables for serum CEA level. CONCLUSIONS: This study suggested that CEA may be
      a mediator that links metabolic disturbance and tumorigenesis in visceral
      obesity. Further studies are required to better understand the clinical and
      pathophysiological significance of our findings.

PMID- 22952700
TI  - Global diversity of marine isopods (except Asellota and crustacean symbionts).
AB  - The crustacean order Isopoda (excluding Asellota, crustacean symbionts and
      freshwater taxa) comprise 3154 described marine species in 379 genera in 37
      families according to the WoRMS catalogue. The history of taxonomic discovery
      over the last two centuries is reviewed. Although a well defined order with the
      Peracarida, their relationship to other orders is not yet resolved but
      systematics of the major subordinal taxa is relatively well understood. Isopods
      range in size from less than 1 mm to Bathynomus giganteus at 365 mm long. They
      inhabit all marine habitats down to 7280 m depth but with few doubtful exceptions
      species have restricted biogeographic and bathymetric ranges. Four feeding
      categories are recognised as much on the basis of anecdotal evidence as hard
      data: detritus feeders and browsers, carnivores, parasites, and filter feeders.
      Notable among these are the Cymothooidea that range from predators and scavengers
      to external blood-sucking micropredators and parasites. Isopods brood 10-1600
      eggs depending on individual species. Strong sexual dimorphism is characteristic
      of several families, notably in Gnathiidae where sessile males live with a harem
      of females while juvenile praniza stages are ectoparasites of fish. Protandry is
      known in Cymothoidae and protogyny in Anthuroidea. Some Paranthuridae are
      neotenous. About half of all coastal, shelf and upper bathyal species have been
      recorded in the MEOW temperate realms, 40% in tropical regions and the remainder
      in polar seas. The greatest concentration of temperate species is in Australasia;
      more have been recorded from temperate North Pacific than the North Atlantic. Of
      tropical regions, the Central Indo-Pacific is home to more species any other
      region. Isopods are decidedly asymmetrical latitudinally with 1.35 times as many
      species in temperate Southern Hemisphere than the temperate North Atlantic and
      northern Pacific, and almost four times as many Antarctic as Arctic species. More
      species are known from the bathyal and abyssal Antarctic than Arctic GOODS
      provinces, and more from the larger Pacific than Atlantic oceans. Two areas with
      many species known are the New Zealand-Kermadec and the Northern North Pacific
      provinces. Deep hard substrates such as found on seamounts and the slopes are
      underrepresented in samples. This, the documented numbers of undescribed species
      in recent collections and probable cryptic species suggest a large as yet
      undocumented fauna, potentially an order of magnitude greater than presently
      known.

PMID- 22952701
TI  - Enhanced persistency of resting and active periods of locomotor activity in
      schizophrenia.
AB  - Patients with schizophrenia frequently exhibit behavioral abnormalities
      associated with its pathological symptoms. Therefore, a quantitative evaluation
      of behavioral dynamics could contribute to objective diagnoses of schizophrenia.
      However, such an approach has not been fully established because of the absence
      of quantitative biobehavioral measures. Recently, we studied the dynamical
      properties of locomotor activity, specifically how resting and active periods are
      interwoven in daily life. We discovered universal statistical laws ("behavioral
      organization") and their alterations in patients with major depressive disorder.
      In this study, we evaluated behavioral organization of schizophrenic patients (n
      = 19) and healthy subjects (n = 11) using locomotor activity data, acquired by
      actigraphy, to investigate whether the laws could provide objective and
      quantitative measures for a possible diagnosis and assessment of symptoms.
      Specifically, we evaluated the cumulative distributions of resting and active
      periods, defined as the periods with physical activity counts successively below
      and above a predefined threshold, respectively. Here we report alterations in the
      laws governing resting and active periods; resting periods obeyed a power-law
      cumulative distribution with significantly lower parameter values (power-law
      scaling exponents), whereas active periods followed a stretched exponential
      distribution with significantly lower parameter values (stretching exponents), in
      patients. Our findings indicate enhanced persistency of both lower and higher
      locomotor activity periods in patients with schizophrenia, probably reflecting
      schizophrenic pathophysiology.

PMID- 22952702
TI  - Leukotriene D4 and interleukin-13 cooperate to increase the release of eotaxin-3
      by airway epithelial cells.
AB  - INTRODUCTION: Airway epithelial cells play a central role in the physiopathology
      of asthma. They release eotaxins when treated with T(H)2 cytokines such as
      interleukin (IL)-4 or IL-13, and these chemokines attract eosinophils and
      potentiate the biosynthesis of cysteinyl leukotrienes (cysLTs), which in turn
      induce bronchoconstriction and mucus secretion. These effects of cysLTs mainly
      mediated by CysLT(1) and CysLT(2) receptors on epithelial cell functions remain
      largely undefined. Because the release of inflammatory cytokines, eotaxins, and
      cysLTs occur relatively at the same time and location in the lung tissue, we
      hypothesized that they regulate inflammation cooperatively rather than
      redundantly. We therefore investigated whether cysLTs and the T(H)2 cytokines
      would act in concert to augment the release of eotaxins by airway epithelial
      cells. METHODS: A549 cells or human primary bronchial epithelial cells were
      incubated with or without IL-4, IL-13, and/or LTD(4). The release of eotaxin-3
      and the expression of cysLT receptors were assessed by ELISA, RT-PCR, and flow
      cytometry, respectively. RESULTS: IL-4 and IL-13 induced the release of eotaxin-3
      by airway epithelial cells. LTD(4) weakly induced the release of eotaxin-3 but
      clearly potentiated the IL-13-induced eotaxin-3 release. LTD(4) had no effect on
      IL-4-stimulated cells. Epithelial cells expressed CysLT(1) but not CysLT(2).
      CysLT(1) expression was increased by IL-13 but not by IL-4 and/or LTD(4).
      Importantly, the upregulation of CysLT(1) by IL-13 preceded eotaxin-3 release.
      CONCLUSIONS: These results demonstrate a stepwise cooperation between IL-13 and
      LTD(4). IL-13 upregulates CysLT(1) expression and consequently the response to
      cysLTs This results in an increased release of eotaxin-3 by epithelial cells
      which at its turn increases the recruitment of leukocytes and their biosynthesis
      of cysLTs. This positive amplification loop involving epithelial cells and
      leukocytes could be implicated in the recruitment of eosinophils observed in
      asthmatics.

PMID- 22952703
TI  - Adoption of rapid diagnostic tests for the diagnosis of malaria, a preliminary
      analysis of the Global Fund program data, 2005 to 2010.
AB  - INTRODUCTION: The World Health Organization Guidelines for the Treatment of
      Malaria, in 2006 and 2010, recommend parasitological confirmation of malaria
      before commencing treatment. Although microscopy has been the mainstay of malaria
      diagnostics, the magnitude of diagnostic scale up required to follow the
      Guidelines suggests that rapid diagnostic tests (RDTs) will be a large component.
      This study analyzes the adoption of rapid diagnostic testing in malaria programs
      supported by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global
      Fund), the leading international funder of malaria control globally. METHODS AND
      FINDINGS: We analyzed, for the period 2005 to 2010, Global Fund programmatic data
      for 81 countries on the quantity of RDTs planned; actual quantities of RDTs and
      artemisinin-based combination treatments (ACTs) procured in 2009 and 2010; RDT
      related activities including RDTs distributed, RDTs used, total diagnostic tests
      including RDTs and microscopy performed, health facilities equipped with RDTs;
      personnel trained to perform rapid diagnostic malaria test; and grant budgets
      allocated to malaria diagnosis. In 2010, diagnosis accounted for 5.2% of malaria
      grant budget. From 2005 to 2010, the procurement plans include148 million RDTs
      through 96 malaria grants in 81 countries. Around 115 million parasitological
      tests, including RDTs, had reportedly been performed from 2005 to 2010. Over this
      period, 123,132 health facilities were equipped with RDTs and 137,140 health
      personnel had been trained to perform RDT examinations. In 2009 and 2010, 41
      million RDTs and 136 million ACTs were purchased. The ratio of procured RDTs to
      ACTs was 0.26 in 2009 and 0.34 in 2010. CONCLUSIONS/SIGNIFICANCE: Global Fund
      financing has enabled 81 malaria-endemic countries to adopt WHO guidelines by
      investing in RDTs for malaria diagnosis, thereby helping improve case management
      of acute febrile illness in children. However, roll-out of parasitological
      diagnosis lags behind the roll-out of ACT-based treatment, and will require
      prioritization of investments.

PMID- 22952704
TI  - Poor prognosis of gastric adenocarcinoma with decreased expression of AHRR.
AB  - BACKGROUND: The aryl hydrocarbon receptor (AHR) repressor (AHRR), a member of
      growing superfamily, is a basic-helix-loop-helix/Per-AHR nuclear translocator
      (ARNT)-Sim (bHLH-PAS) protein. Recently, AHRR has been proposed to function as a
      putative new tumor suppressor gene based on some relevant studies in multiple
      types of human cancers. This current study aims to investigate AHHR expression
      and its prognostic significance in primary gastric adenocarcinoma.
      METHODOLOGY/PRINCIPAL FINDINGS: The expression level of AHRR was analyzed using
      real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical
      staining. It was clearly showed that the expression status of AHRR was reduced in
      tumor tissue samples compared with that in matched adjacent non-tumor tissue
      samples by RT-qPCR (P = 0.0423) and western blotting analysis (P = 0.004).
      Moreover, data revealed that AHRR without exon 8 (the active isoform) was the
      predominant form either in tumor tissues (66.7%, 8/12) or in matched adjacent non
      tumor tissues (100.0%, 12/12), and the mRNA level of this isoform was
      significantly reduced in tumor tissues (P = 0.006). Immunohistochemistry analysis
      indicated that AHRR expression was significantly decreased in 175 of 410 (42.7%)
      gastric adenocarcinoma cases. Kaplan-Meier survival curves and Multivariate Cox
      analysis revealed that decreased expression of AHRR was significantly associated
      with poor prognosis in gastric adenocarcinoma patients. CONCLUSIONS/SIGNIFICANCE:
      Our data suggests that, in primary gastric adenocarcinoma, AHRR may play as a
      suppressor gene and its expression status has the potential to be an independent
      prognostic factor.

PMID- 22952705
TI  - p53 inactivation upregulates p73 expression through E2F-1 mediated transcription.
AB  - While p73 overexpression has been associated with increased apoptosis in cancer
      tissues, p73 overexpressing tumors appear to be of high grade malignancy. Why
      this putative tumor suppressor is overexpressed in cancer cells and what the
      function of overexpressed p73 is in breast cancers are critical questions to be
      addressed. By investigating the effect of p53 inactivation on p73 expression, we
      found that both protein and mRNA levels of TAp73 were increased in MCF-7/p53siRNA
      cells, MCF-7/p53mt135 cells and HCT-116/p53-/- cells, as compared to wild type
      control, suggesting that p53 inactivation by various forms upregulates p73. We
      showed that p53 knockdown induced p73 was mainly regulated at the transcriptional
      level. However, although p53 has a putative binding site in the TAp73 promoter,
      deletion of this binding site did not affect p53 knockdown mediated activation of
      TAp73 promoter. Chromatin immuno-precipitation (ChIP) data demonstrated that loss
      of p53 results in enhanced occupancy of E2F-1 in the TAp73 promoter. The
      responsive sequence of p53 inactivation mediated p73 upregulation was mapped to
      the proximal promoter region of the TAp73 gene. To test the role of E2F-1 in p53
      inactivation mediated regulation of p73 transcription, we found that p53
      knockdown enhanced E2F-1 dependent p73 transcription, and mutations in E2F-1
      binding sites in the TAp73 promoter abrogated p53 knockdown mediated activation
      of TAp73 promoter. Moreover, we demonstrated that p21 is a mediator of p53-E2F
      crosstalk in the regulation of p73 transcription. We concluded that p53
      knockdown/inactivation may upregulate TAp73 expression through E2F-1 mediated
      transcriptional regulation. p53 inactivation mediated upregulation of p73
      suggests an intrinsic rescuing mechanism in response to p53
      mutation/inactivation. These findings support further analysis of the correlation
      between p53 status and p73 expression and its prognostic/predictive significance
      in human cancers.

PMID- 22952706
TI  - Foraging in the darkness of the Southern Ocean: influence of bioluminescence on a
      deep diving predator.
AB  - How non-echolocating deep diving marine predators locate their prey while
      foraging remains mostly unknown. Female southern elephant seals (SES) (Mirounga
      leonina) have vision adapted to low intensity light with a peak sensitivity at
      485 nm. This matches the wavelength of bioluminescence produced by a large range
      of marine organisms including myctophid fish, SES's main prey. In this study, we
      investigated whether bioluminescence provides an accurate estimate of prey
      occurrence for SES. To do so, four SES were satellite-tracked during their post
      breeding foraging trip and were equipped with Time-Depth-Recorders that also
      recorded light levels every two seconds. A total of 3386 dives were processed
      through a light-treatment model that detected light events higher than ambient
      level, i.e. bioluminescence events. The number of bioluminescence events was
      related to an index of foraging intensity for SES dives deep enough to avoid the
      influence of natural ambient light. The occurrence of bioluminescence was found
      to be negatively related to depth both at night and day. Foraging intensity was
      also positively related to bioluminescence both during day and night. This result
      suggests that bioluminescence likely provides SES with valuable indications of
      prey occurrence and might be a key element in predator-prey interactions in deep
      dark marine environments.

PMID- 22952707
TI  - Extensive natural variation for cellular hydrogen peroxide release is genetically
      controlled.
AB  - Natural variation in DNA sequence contributes to individual differences in
      quantitative traits. While multiple studies have shown genetic control over gene
      expression variation, few additional cellular traits have been investigated.
      Here, we investigated the natural variation of NADPH oxidase-dependent hydrogen
      peroxide (H(2)O(2) release), which is the joint effect of reactive oxygen species
      (ROS) production, superoxide metabolism and degradation, and is related to a
      number of human disorders. We assessed the normal variation of H(2)O(2) release
      in lymphoblastoid cell lines (LCL) in a family-based 3-generation cohort (CEPH
      HapMap), and in 3 population-based cohorts (KORA, GenCord, HapMap). Substantial
      individual variation was observed, 45% of which were associated with heritability
      in the CEPH-HapMap cohort. We identified 2 genome-wide significant loci of Hsa12
      and Hsa15 in genome-wide linkage analysis. Next, we performed genome-wide
      association study (GWAS) for the combined KORA-GenCord cohorts (n = 279) using
      enhanced marker resolution by imputation (>1.4 million SNPs). We found 5
      significant associations (p<5.00*10-8) and 54 suggestive associations (p<1.00*10
      5), one of which confirmed the linked region on Hsa15. To replicate our findings,
      we performed GWAS using 58 HapMap individuals and ~2.1 million SNPs. We
      identified 40 genome-wide significant and 302 suggestive SNPs, and confirmed
      genome signals on Hsa1, Hsa12, and Hsa15. Genetic loci within 900 kb from the
      known candidate gene p67phox on Hsa1 were identified in GWAS in both cohorts. We
      did not find replication of SNPs across all cohorts, but replication within the
      same genomic region. Finally, a highly significant decrease in H(2)O(2) release
      was observed in Down Syndrome (DS) individuals (p<2.88*10-12). Taken together,
      our results show strong evidence of genetic control of H(2)O(2) in LCL of healthy
      and DS cohorts and suggest that cellular phenotypes, which themselves are also
      complex, may be used as proxies for dissection of complex disorders.

PMID- 22952708
TI  - HIV and STI prevalence and determinants among male migrant workers in India.
AB  - BACKGROUND: Our objective was to estimate for the first time the prevalence and
      determinants of human immunodeficiency virus type 1 (HIV-1) and sexually
      transmitted infections (STIs) among male migrants in India. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a multi-stage stratified probability sample survey of
      migrant (defined as not born in Surat city) men aged 18 to 49 years working in
      the diamond and textile industries in Surat city. Behavioural and biological data
      were collected. Biological data included laboratory diagnosed herpes simplex
      virus type 2 (HSV-2), syphilis, chlamydia, gonorrhoea, Trichomonas vaginalis
      (together defined as 'any STI') and HIV-1. Likely recently acquired STIs included
      chlamydia, gonorrhoea, T. vaginalis and syphilis with rapid plasma reagin >=1:8.
      The response rate was 77% (845/1099). Among 841 participants, HIV-1 prevalence
      was 1.0%, 'any STI' prevalence was 9.5% and 38.9% of these STIs were likely to
      have been recently acquired. Being a diamond worker, Surat resident for 10+ years
      and recent antibiotic use were each associated with higher odds of 'any STI'
      (aORs 1.83 (95% CI 1.09-3.09), 1.98 (95% CI 1.22-3.22) and 2.57 (95% CI 1 .17
      5.64), respectively) after adjusting for the other two factors and age. The main
      study limitation was social desirability bias for self-reported sexual behaviour;
      STIs were diagnosed in some self-reported virgins. CONCLUSIONS/SIGNIFICANCE: HIV
      and STI prevalence were lower than expected, but prevention interventions remain
      necessary in Surat since almost 40% of STIs among participants were probably
      recently acquired and sentinel surveillance HIV prevalence remains high. The
      participants had a similar HIV prevalence to Surat antenatal clinic attendees, a
      proxy for the general population. This suggests migrants are not always at higher
      risk of HIV compared to the general population in their migration destination.
      Our findings highlight the need to contextualise research findings from a
      specific setting with other local information to guide HIV/STI prevention
      interventions.

PMID- 22952709
TI  - Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro
      and in preclinical mouse model.
AB  - Ovarian cancer is the leading cause of cancer related deaths in women. Genetic
      alterations including overexpression of EGFR play a crucial role in ovarian
      carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC)
      in ovarian tumor cells in vitro and in vivo. Oral administration of 12 umol PEITC
      resulted in drastically suppressing ovarian tumor growth in a preclinical mouse
      model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV
      3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a
      concentration-dependent manner. Growth inhibitory effects of PEITC were mediated
      by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian
      tumors. PEITC treatment caused significant down regulation of constitutive
      protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian
      cancer cells. In addition, PEITC treatment drastically reduced the
      phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling.
      PEITC treatment also inhibited the kinase activity of AKT as observed by the down
      regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF
      treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results
      suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our
      study suggests that PEITC could be used alone or in combination with other
      therapeutic agents to treat ovarian cancer.

PMID- 22952710
TI  - Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular
      assay for LRRK2 Ser935 phosphorylation.
AB  - BACKGROUND: Mutations in the leucine-rich repeat kinase-2 (LRRK2) have been
      linked to Parkinson's disease. Recent studies show that inhibition of LRRK2
      kinase activity decreased the level of phosphorylation at its own Ser910 and
      Ser935, indicating that these sites are prime targets for cellular readouts of
      LRRK2 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: Using Time-Resolved Forster
      Resonance Energy Transfer (TR-FRET) technology, we developed a high-throughput
      cellular assay for monitoring LRRK2 phosphorylation at Ser935. LRRK2-Green
      Fluorescence Protein (GFP) fusions were expressed in cells via BacMam.
      Phosphorylation at Ser935 in these cells is detected using a terbium labeled anti
      phospho-Ser935 antibody that generates a TR-FRET signal between terbium and GFP.
      LRRK2 wild-type and G2019S are constitutively phosphorylated at Ser935 in cells
      as measured by TR-FRET. The phosphorylation level is reduced for the R1441C
      mutant and little could be detected for the kinase-dead mutant D1994A. The TR
      FRET cellular assay was further validated using reported LRRK2 inhibitors
      including LRRK2-IN-1 and our results confirmed that inhibition of LRRK2 can
      reduce the phosphorylation level at Ser935. To demonstrate the utility of this
      assay for screening, we profiled a small library of 1120 compounds. Three known
      LRRK2 inhibitors were identified and 16 hits were followed up in the TR-FRET and
      a cytotoxicity assay. Interestingly, out of the top 16 hits, five are known
      inhibitors of IkappaB phosphorylation, two CHK1 and two CDC25 inhibitors.
      Thirteen hits were further tested in a biochemical LRRK2 kinase activity assay
      and Western blot analysis for their effects on the phosphorylation of Ser910,
      Ser935, Ser955 and Ser973. CONCLUSIONS/SIGNIFICANCE: We developed a TR-FRET
      cellular assay for LRRK2 Ser935 phosphorylation that can be applied to the
      screening for LRRK2 inhibitors. We report for the first time that several
      compounds such as IKK16, CHK1 inhibitors and GW441756 can inhibit LRRK2 Ser935
      phosphorylation in cells and LRRK2 kinase activity in vitro.

PMID- 22952711
TI  - Candidate gene approach identifies multiple genes and signaling pathways
      downstream of Tbx4 in the developing allantois.
AB  - Loss of Tbx4 results in absence of chorio-allantoic fusion and failure of
      formation of the primary vascular plexus of the allantois leading to embryonic
      death at E10.5. We reviewed the literature for genes implicated in chorio
      allantoic fusion, cavitation and vascular plexus formation, processes affected in
      Tbx4 mutant allantoises. Using this candidate gene approach, we identified a
      number of genes downstream of Tbx4 in the allantois including extracellular
      matrix molecules Vcan, Has2, and Itgalpha5, transcription factors Snai1 and
      Twist, and signaling molecules Bmp2, Bmp7, Notch2, Jag1 and Wnt2. In addition, we
      show that the canonical Wnt signaling pathway contributes to the vessel-forming
      potential of the allantois. Ex vivo, the Tbx4 mutant phenotype can be rescued
      using agonists of the Wnt signaling pathway and, in wildtype allantoises, an
      inhibitor of the canonical Wnt signaling pathway disrupts vascular plexus
      formation. In vivo, Tbx4 and Wnt2 double heterozygous placentas show decreased
      vasculature suggesting interactions between Tbx4 and the canonical Wnt signaling
      pathway in the process of allantois-derived blood vessel formation.

PMID- 22952712
TI  - Measuring ambiguity in HLA typing methods.
AB  - In hematopoietic stem cell transplantation, donor selection is based primarily on
      matching donor and patient HLA genes. These genes are highly polymorphic and
      their typing can result in exact allele assignment at each gene (the resolution
      at which patients and donors are matched), but it can also result in a set of
      ambiguous assignments, depending on the typing methodology used. To facilitate
      rapid identification of matched donors, registries employ statistical algorithms
      to infer HLA alleles from ambiguous genotypes. Linkage disequilibrium information
      encapsulated in haplotype frequencies is used to facilitate prediction of the
      most likely haplotype assignment. An HLA typing with less ambiguity produces
      fewer high-probability haplotypes and a more reliable prediction. We estimated
      ambiguity for several HLA typing methods across four continental populations
      using an information theory-based measure, Shannon's entropy. We used allele and
      haplotype frequencies to calculate entropy for different sets of 1,000 subjects
      with simulated HLA typing. Using allele frequencies we calculated an average
      entropy in Caucasians of 1.65 for serology, 1.06 for allele family level, 0.49
      for a 2002-era SSO kit, and 0.076 for single-pass SBT. When using haplotype
      frequencies in entropy calculations, we found average entropies of 0.72 for
      serology, 0.73 for allele family level, 0.05 for SSO, and 0.002 for single-pass
      SBT. Application of haplotype frequencies further reduces HLA typing ambiguity.
      We also estimated expected confirmatory typing mismatch rates for simulated
      subjects. In a hypothetical registry with all donors typed using the same method,
      the entropy values based on haplotype frequencies correspond to confirmatory
      typing mismatch rates of 1.31% for SSO versus only 0.08% for SBT. Intermediate
      resolution single-pass SBT contains the least ambiguity of the methods we
      evaluated and therefore the most certainty in allele prediction. The presented
      measure objectively evaluates HLA typing methods and can help define acceptable
      HLA typing for donor recruitment.

PMID- 22952713
TI  - Mechanisms and determinants of ultralong action potential duration and slow rate
      dependence in cardiac myocytes.
AB  - In normal cardiac myocytes, the action potential duration (APD) is several
      hundred milliseconds. However, experimental studies showed that under certain
      conditions, APD could be excessively long (or ultralong), up to several seconds.
      Unlike the normal APD, the ultralong APD increases sensitively with pacing cycle
      length even when the pacing rate is very slow, exhibiting a sensitive slow rate
      dependence. In addition, these long action potentials may or may not exhibit
      early afterdepolarizations (EADs). Although these phenomena are well known, the
      underlying mechanisms and ionic determinants remain incompletely understood. In
      this study, computer simulations were performed with a simplified action
      potential model. Modifications to the L-type calcium current (I(Ca,L)) kinetics
      and the activation time constant of the delayed rectifier K current were used to
      investigate their effects on APD. We show that: 1) the ultralong APD and its
      sensitive slow rate-dependence are determined by the steady-state window and
      pedestal I(Ca,L) currents and the activation speed and the recovery of the
      delayed rectifier K current; 2) whether an ultralong action potential exhibits
      EADs or not depends on the kinetics of I(Ca,L); 3) increasing inward currents
      elevates the plateau voltage, which in general prolongs APD, however, this can
      also shorten APD when the APD is already ultralong under certain conditions; and
      4) APD alternans occurs at slow pacing rates due to the sensitive slow rate
      dependence and the ionic determinants are different from the ones causing APD
      alternans at fast heart rates.

PMID- 22952714
TI  - A novel five gene signature derived from stem-like side population cells predicts
      overall and recurrence-free survival in NSCLC.
AB  - Gene expression profiling has been used to characterize prognosis in various
      cancers. Earlier studies had shown that side population cells isolated from Non
      Small Cell Lung Cancer (NSCLC) cell lines exhibit cancer stem cell properties. In
      this study we apply a systems biology approach to gene expression profiling data
      from cancer stem like cells isolated from lung cancer cell lines to identify
      novel gene signatures that could predict prognosis. Microarray data from side
      population (SP) and main population (MP) cells isolated from 4 NSCLC lines (A549,
      H1650, H460, H1975) were used to examine gene expression profiles associated with
      stem like properties. Differentially expressed genes that were over or under
      expressed at least two fold commonly in all 4 cell lines were identified. We
      found 354 were upregulated and 126 were downregulated in SP cells compared to MP
      cells; of these, 89 up and 62 downregulated genes (average 2 fold changes) were
      used for Principle Component Analysis (PCA) and MetaCore pathway analysis. The
      pathway analysis demonstrated representation of 4 up regulated genes (TOP2A,
      AURKB, BRRN1, CDK1) in chromosome condensation pathway and 1 down regulated gene
      FUS in chromosomal translocation. Microarray data was validated using qRT-PCR on
      the 5 selected genes and all showed robust correlation between microarray and qRT
      PCR. Further, we analyzed two independent gene expression datasets that included
      360 lung adenocarcinoma patients from NCI Director's Challenge Set for overall
      survival and 63 samples from Sungkyunkwan University (SKKU) for recurrence free
      survival. Kaplan-Meier and log-rank test analysis predicted poor survival of
      patients in both data sets. Our results suggest that genes involved in chromosome
      condensation are likely related with stem-like properties and might predict
      survival in lung adenocarcinoma. Our findings highlight a gene signature for
      effective identification of lung adenocarcinoma patients with poor prognosis and
      designing more aggressive therapies for such patients.

PMID- 22952716
TI  - Transport properties of melanosomes along microtubules interpreted by a tug-of
      war model with loose mechanical coupling.
AB  - In this work, we explored theoretically the transport of organelles driven along
      microtubules by molecular motors of opposed polarities using a stochastic model
      that considers a Langevin dynamics for the cargo, independent cargo-motor linkers
      and stepping motion for the motors. It has been recently proposed that the
      stiffness of the motor plays an important role when multiple motors collectively
      transport a cargo. Therefore, we considered in our model the recently reported
      values for the stiffness of the cargo-motor linker determined in living cells
      (~0.01 pN/nm,) which is significantly lower than the motor stiffness obtained in
      in vitro assays and used in previous studies. Our model could reproduce the
      multimodal velocity distributions and typical trajectory characteristics
      including the properties of the reversions in the overall direction of motion
      observed during melanosome transport along microtubules in Xenopus laevis
      melanophores. Moreover, we explored the contribution of the different motility
      states of the cargo-motor system to the different modes of the velocity
      distributions and could identify the microscopic mechanisms of transport leading
      to trajectories compatible with those observed in living cells. Finally, by
      changing the attachment and detachment rates, the model could reproduce the
      different velocity distributions observed during melanosome transport along
      microtubules in Xenopus laevis melanophores stimulated for aggregation and
      dispersion. Our analysis suggests that active tug-of-war processes with loose
      mechanical coupling can account for several aspects of cargo transport along
      microtubules in living cells.

PMID- 22952715
TI  - Biosignatures for Parkinson's disease and atypical parkinsonian disorders
      patients.
AB  - Diagnosis of Parkinson' disease (PD) carries a high misdiagnosis rate due to
      failure to recognize atypical parkinsonian disorders (APD). Usually by the time
      of diagnosis greater than 60% of the neurons in the substantia nigra are dead.
      Therefore, early detection would be beneficial so that therapeutic intervention
      may be initiated early in the disease process. We used splice variant-specific
      microarrays to identify mRNAs whose expression is altered in peripheral blood of
      early-stage PD patients compared to healthy and neurodegenerative disease
      controls. Quantitative polymerase chain reaction assays were used to validate
      splice variant transcripts in independent sample sets. Here we report a PD
      signature used to classify blinded samples with 90% sensitivity and 94%
      specificity and an APD signature that resulted in a diagnosis with 95%
      sensitivity and 94% specificity. This study provides the first discriminant
      functions with coherent diagnostic signatures for PD and APD. Analysis of the PD
      biomarkers identified a regulatory network with nodes centered on the
      transcription factors HNF4A and TNF, which have been implicated in insulin
      regulation.

PMID- 22952717
TI  - Early reduction of microglia activation by irradiation in a model of chronic
      glaucoma.
AB  - Glaucoma is a neurodegenerative disease that results in the progressive decline
      and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors
      are associated with glaucoma, the mechanisms leading to onset and progression of
      the disease remain unknown. Molecular analysis in various glaucoma models has
      revealed involvement of non-neuronal cell populations, including astrocytes,
      Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation
      was reported to have a significant long-term protective effect in the DBA/2J (D2)
      mouse model of glaucoma, although the cellular and molecular basis for this
      effect remains unclear. In particular, the acute effects of irradiation on
      specific cell populations, including non-neuronal cells, in the D2 retina and
      nerve have not been assessed. Here we report that irradiation induces transient
      reduction in proliferating microglia within the optic nerve head and glial lamina
      within the first week post-irradiation. This was accompanied by reduced
      microglial activation, with no effect on astrocyte gliosis in those regions. At
      later stages we confirm that early high-dose irradiation of the mouse head
      results in improvement of axonal structural integrity and anterograde transport
      function, without reduction of intraocular pressure. Thus reduced microglial
      activation induced by irradiation at early stages is associated with reduced
      optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.

PMID- 22952718
TI  - Transcriptional regulation of hTREX84 in human cancer cells.
AB  - TREX (transcription/export) is a multiprotein complex that plays a key role in
      the transcriptional elongation and transport of mRNA from the nucleus to the
      cytoplasm. We previously reported the purification of the human TREX protein and
      found that expression of a member of this complex, p84N5 (referred to as hTREX84
      or hHPR1), a RB binding protein, correlated with breast tumor size and
      metastasis. Here we examine the mechanisms of aberrant expression of hTREX84 in
      breast and ovarian cancer cells and evaluate its role in tumorigenesis. We show
      that ovarian tumor cells over-express hTREX84 4-fold and 10-fold compared to
      immortal, non-tumorigenic and primary ovarian surface epithelial cells,
      respectively. Reduction of hTREX84 levels by small interfering RNA result in
      inhibition of cellular proliferation and G(2/M) arrest. Even though we observed
      that hTREX84 expression was induced by treatment with a demethylation agent, 5
      aza-2'-deoxycytidine (5-aza-dC), sodium bisulfite DNA sequencing and methylation
      specific PCR found no evidence of changes in DNA methylation in the CpG islands
      in the regulator region of hTREX84. We subsequently identify several
      transcriptional factors, including NF-kappaB binding sites in the hTREX84 gene
      promoter and demonstrate by chromatin immunoprecipation (ChIP) and site directed
      mutagenesis that RelA/p65 binds the NF-kB binding sites and induces hTREX84
      expression. Finally, we show by immunohistochemistry (IHC) that RelA/p65 is
      abundantly expressed in malignant cells that aberrantly express hTREX84
      indicating that RelA/p65 might play a pivotal role in regulating hTREX84
      expression in cancer. Our results indicate that overexpression of hTREX84 is
      associated with cancer cell transformation, proliferation and may be regulated by
      RelA/p65.

PMID- 22952719
TI  - Comparison: Flu prescription sales data from a retail pharmacy in the US with
      Google Flu trends and US ILINet (CDC) data as flu activity indicator.
AB  - The potential threat of bioterrorism along with the emergence of new or existing
      drug resistant strains of influenza virus, added to expanded global travel, have
      increased vulnerability to epidemics or pandemics and their aftermath. The same
      factors have also precipitated urgency for having better, faster, sensitive, and
      reliable syndromic surveillance systems. Prescription sales data can provide
      surrogate information about the development of infectious diseases and therefore
      serve as a useful tool in syndromic surveillance. This study compared
      prescription sales data from a large drug retailing pharmacy chain in the United
      States with Google Flu trends surveillance system data as a flu activity
      indicator. It was found that the two were highly correlated. The correlation
      coefficient (Pearson 'r') for five years' aggregate data (2007-2011) was 0.92
      (95% CI, 0.90-0.94). The correlation coefficients for each of the five years
      between 2007 and 2011 were 0.85, 0.92, 0.91, 0.88, and 0.87 respectively.
      Additionally, prescription sales data from the same large drug retailing pharmacy
      chain in the United States were also compared with US Outpatient Influenza-like
      Illness Surveillance Network (ILINet) data for 2007 by Centers for Disease
      Control and Prevention (CDC). The correlation coefficient (Pearson 'r') was 0.97
      (95% CI, 0.95-0.98).

PMID- 22952720
TI  - Potent adjuvanticity of a pure TLR7-agonistic imidazoquinoline dendrimer.
AB  - Engagement of toll-like receptors (TLRs) serve to link innate immune responses
      with adaptive immunity and can be exploited as powerful vaccine adjuvants for
      eliciting both primary and anamnestic immune responses. TLR7 agonists are highly
      immunostimulatory without inducing dominant proinflammatory cytokine responses.
      We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8
      dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would
      result in altered activity profiles. A complete loss of TLR8-stimulatory activity
      with selective retention of the TLR7-agonistic activity was observed in the
      dendrimer. This was reflected by a complete absence of TLR8-driven
      proinflammatory cytokine and interferon (IFN)-gamma induction in human PBMCs,
      with preservation of TLR7-driven IFN-alpha induction. The dendrimer was found to
      be superior to the imidazoquinoline monomer in inducing high titers of high
      affinity antibodies to bovine alpha-lactalbumin. Additionally, epitope mapping
      experiments showed that the dendrimer induced immunoreactivity to more contiguous
      peptide epitopes along the amino acid sequence of the model antigen.

PMID- 22952721
TI  - Synovial fluid progenitors expressing CD90+ from normal but not osteoarthritic
      joints undergo chondrogenic differentiation without micro-mass culture.
AB  - OBJECTIVE: Mesenchymal progenitor cells (MPCs) can differentiate into
      osteoblasts, adipocytes, and chondrocytes, and are in part responsible for
      maintaining tissue integrity. Recently, a progenitor cell population has been
      found within the synovial fluid that shares many similarities with bone marrow
      MPCs. These synovial fluid MPCs (sfMPCs) share the ability to differentiate into
      bone and fat, with a bias for cartilage differentiation. In this study, sfMPCs
      were isolated from human and canine synovial fluid collected from normal
      individuals and those with osteoarthritis (human: clinician-diagnosed, canine:
      experimental) to compare the differentiation potential of CD90+ vs. CD90- sfMPCs,
      and to determine if CD90 (Thy-1) is a predictive marker of synovial fluid
      progenitors with chondrogenic capacity in vitro. METHODS: sfMPCs were derived
      from synovial fluid from normal and OA knee joints. These cells were induced to
      differentiate into chondrocytes and analyzed using quantitative PCR,
      immunofluorescence, and electron microscopy. RESULTS: The CD90+ subpopulation of
      sfMPCs had increased chondrogenic potential compared to the CD90- population.
      Furthermore, sfMPCs derived from healthy joints did not require a micro-mass step
      for efficient chondrogenesis. Whereas sfMPCs from OA synovial fluid retain the
      ability to undergo chondrogenic differentiation, they require micro-mass culture
      conditions. CONCLUSIONS: Overall, this study has demonstrated an increased
      chondrogenic potential within the CD90+ fraction of human and canine sfMPCs and
      that this population of cells derived from healthy normal joints do not require a
      micro-mass step for efficient chondrogenesis, while sfMPCs obtained from OA knee
      joints do not differentiate efficiently into chondrocytes without the micro-mass
      procedure. These results reveal a fundamental shift in the chondrogenic ability
      of cells isolated from arthritic joint fluids, and we speculate that the
      mechanism behind this change of cell behavior is exposure to the altered milieu
      of the OA joint fluid, which will be examined in further studies.

PMID- 22952722
TI  - The new invincibles: HIV screening among older adults in the U.S.
AB  - BACKGROUND: Thirteen percent of the U.S. population is ages 65 and older, a
      number projected to reach 20% by 2030. By 2015, 50% of Human Immunodeficiency
      Virus (HIV)-infected individuals in the U.S. are expected to be ages 50 and
      older. Current Centers for Disease Control and Prevention guidelines recommend
      "opt-out" HIV screening for individuals ages 13-64. The purpose of this study was
      to assess the occurrence and barriers to HIV screening in older adults, and to
      evaluate the rationale for expanding routine HIV screening to this population.
      METHODS: The study used 2009 National Health Interview Survey (NHIS) data. A
      total of 12,366 (unweighted) adults, ages 50 and older, participated in the adult
      section of the NHIS and answered questions on the HIV/AIDS, Sexually Transmitted
      Diseases, and Tuberculosis components. Associations between HIV screening, socio
      demographic variables, and knowledge of HIV-related disease were examined using
      logistic regression models. RESULTS: The HIV screening rate within this
      population was 25.4%. Race had no statistically significant effect. Low risk
      perception of HIV exposure (84.1%) accounted for low likelihood of planned
      screening (3.5%) within 12 months post survey. A routine medical check-up was the
      single most common reason for HIV screening (37.6%), with only about half (52.7%)
      of the tests suggested by a health care provider. CONCLUSION: It is imperative
      that practices and policies are developed and implemented to increase HIV
      awareness and screening in the older adult population. Increased health care
      provider awareness of the importance of HIV screening, especially for those 65
      and older, is critical. Health policies and clinical guidelines should be revised
      to promote and support screening of all adults.

PMID- 22952723
TI  - Effects of age and parity on mammary gland lesions and progenitor cells in the
      FVB/N-RC mice.
AB  - The FVB/N mouse strain is extensively used in the development of animal models
      for breast cancer research. Recently it has been reported that the aging FVB/N
      mice develop spontaneous mammary lesions and tumors accompanied with
      abnormalities in the pituitary glands. These observations have a great impact on
      the mouse models of human breast cancer. We have developed a population of inbred
      FVB/N mice (designated FVB/N-RC) that have been genetically isolated for 20
      years. To study the effects of age and parity on abnormalities of the mammary
      glands of FVB/N-RC mice, twenty-five nulliparous and multiparous (3-4
      pregnancies) females were euthanized at 16-22 months of age. Examination of the
      mammary glands did not reveal macroscopic evidence of mammary gland tumors in
      either aged-nulliparous or multiparous FVB/N-RC mice (0/25). However,
      histological analysis of the mammary glands showed rare focal nodules of squamous
      changes in 2 of the aged multiparous mice. Mammary gland hyperplasia was detected
      in 8% and 71% of the aged-nulliparous and aged-multiparous mice, respectively.
      Epithelial contents and serum levels of triiodothyronine were significantly
      higher in the experimental groups than the 14-wk-old control mice. Immuno
      histochemical staining of the pituitary gland pars distalis showed no difference
      in prolactin staining between the control and the aged mice. Tissue transplant
      and dilution studies showed no effect of age and/or parity on the ability of
      putative progenitor cells present among the injected mammary cells to repopulate
      a cleared fat pad and develop a full mammary gland outgrowth. This FVB/N-RC mouse
      substrain is suitable to develop mouse models for breast cancer.

PMID- 22952724
TI  - Phylogenetic and functional metagenomic profiling for assessing microbial
      biodiversity in environmental monitoring.
AB  - Decisions guiding environmental management need to be based on a broad and
      comprehensive understanding of the biodiversity and functional capability within
      ecosystems. Microbes are of particular importance since they drive biogeochemical
      cycles, being both producers and decomposers. Their quick and direct responses to
      changes in environmental conditions modulate the ecosystem accordingly, thus
      providing a sensitive readout. Here we have used direct sequencing of total DNA
      from water samples to compare the microbial communities of two distinct coastal
      regions exposed to different anthropogenic pressures: the highly polluted Port of
      Genoa and the protected area of Montecristo Island in the Mediterranean Sea.
      Analysis of the metagenomes revealed significant differences in both microbial
      diversity and abundance between the two areas, reflecting their distinct
      ecological habitats and anthropogenic stress conditions. Our results indicate
      that the combination of next generation sequencing (NGS) technologies and
      bioinformatics tools presents a new approach to monitor the diversity and the
      ecological status of aquatic ecosystems. Integration of metagenomics into
      environmental monitoring campaigns should enable the impact of the anthropogenic
      pressure on microbial biodiversity in various ecosystems to be better assessed
      and also predicted.

PMID- 22952725
TI  - Biochemical and functional studies of lymphoid-specific tyrosine phosphatase
      (Lyp) variants S201F and R266W.
AB  - The Lymphoid specific tyrosine phosphatase (Lyp) has elicited tremendous research
      interest due to the high risk of its missense mutation R620W in a wide spectrum
      of autoimmune diseases. While initially characterized as a gain-of-function
      mutant, R620W was thought to lead to autoimmune diseases through loss-of-function
      in T cell signaling by a recent study. Here we investigate the biochemical
      characters and T cell signaling functions of two uncharacterized Lyp variants
      S201F and R266W, together with a previously characterized Lyp variant R263Q,
      which had reduced risk in several autoimmune diseases, including systemic lupus
      erythematosus (SLE), ulcerative colitis (UC) and rheumatoid arthritis (RA). Our
      kinetic and functional studies of R263Q polymorphism basically reproduced
      previous findings that it was a loss-of-function mutant. The other variant S201F
      reduced Lyp phosphatase activity moderately and decreased Lyp function in T cell
      slightly, while R266W severely impaired phosphatase activity and was a loss-of
      function variant in T cell signaling. A combined kinetic and structure analysis
      suggests that the R266W variant may decrease its phosphatase activity through
      perturbing either the Q-loop or the WPD loop of Lyp. As both R266W and R263Q
      significantly change their phosphatase activity and T cell functions, future work
      could be considered to evaluate these mutants in a broader spectrum of autoimmune
      diseases.

PMID- 22952726
TI  - Clostridium difficile spore-macrophage interactions: spore survival.
AB  - BACKGROUND: Clostridium difficile is the main cause of nosocomial infections
      including antibiotic associated diarrhea, pseudomembranous colitis and toxic
      megacolon. During the course of Clostridium difficile infections (CDI), C.
      difficile undergoes sporulation and releases spores to the colonic environment.
      The elevated relapse rates of CDI suggest that C. difficile spores has a
      mechanism(s) to efficiently persist in the host colonic environment.
      METHODOLOGY/PRINCIPAL FINDINGS: In this work, we provide evidence that C.
      difficile spores are well suited to survive the host's innate immune system.
      Electron microscopy results show that C. difficile spores are recognized by
      discrete patchy regions on the surface of macrophage Raw 264.7 cells, and
      phagocytosis was actin polymerization dependent. Fluorescence microscopy results
      show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered,
      and that ~60% of C. difficile spores were phagocytosed by Raw 264.7 cells.
      Strikingly, presence of complement decreased Raw 264.7 cells' ability to
      phagocytose C. difficile spores. Due to the ability of C. difficile spores to
      remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of
      macrophage infection. Interestingly, transmission electron micrographs showed
      interactions between the surface proteins of C. difficile spores and the
      phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells
      with C. difficile spores for 48 h produced significant Raw 264.7 cell death as
      demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate that despite efficient
      recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores
      remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7
      cells.

PMID- 22952727
TI  - Convergent adaptations: bitter manioc cultivation systems in fertile
      anthropogenic dark earths and floodplain soils in Central Amazonia.
AB  - Shifting cultivation in the humid tropics is incredibly diverse, yet research
      tends to focus on one type: long-fallow shifting cultivation. While it is a
      typical adaptation to the highly-weathered nutrient-poor soils of the Amazonian
      terra firme, fertile environments in the region offer opportunities for
      agricultural intensification. We hypothesized that Amazonian people have
      developed divergent bitter manioc cultivation systems as adaptations to the
      properties of different soils. We compared bitter manioc cultivation in two
      nutrient-rich and two nutrient-poor soils, along the middle Madeira River in
      Central Amazonia. We interviewed 249 farmers in 6 localities, sampled their
      manioc fields, and carried out genetic analysis of bitter manioc landraces. While
      cultivation in the two richer soils at different localities was characterized by
      fast-maturing, low-starch manioc landraces, with shorter cropping periods and
      shorter fallows, the predominant manioc landraces in these soils were generally
      not genetically similar. Rather, predominant landraces in each of these two
      fertile soils have emerged from separate selective trajectories which produced
      landraces that converged for fast-maturing low-starch traits adapted to
      intensified swidden systems in fertile soils. This contrasts with the more
      extensive cultivation systems found in the two poorer soils at different
      localities, characterized by the prevalence of slow-maturing high-starch
      landraces, longer cropping periods and longer fallows, typical of previous
      studies. Farmers plant different assemblages of bitter manioc landraces in
      different soils and the most popular landraces were shown to exhibit
      significantly different yields when planted in different soils. Farmers have
      selected different sets of landraces with different perceived agronomic
      characteristics, along with different fallow lengths, as adaptations to the
      specific properties of each agroecological micro-environment. These findings open
      up new avenues for research and debate concerning the origins, evolution, history
      and contemporary cultivation of bitter manioc in Amazonia and beyond.

PMID- 22952728
TI  - Angiogenic factors in women ten years after severe very early onset preeclampsia.
AB  - BACKGROUND: Women with a history of mainly severe and early onset preeclampsia
      have an increased risk of future cardiovascular disease. During these complicated
      pregnancies increased levels of anti-angiogenic factors can be found. We
      hypothesize that women with a history of severe very early onset preeclampsia
      still have increased levels of these biomarkers years after this pregnancy,
      resulting in increased risk for cardiovascular disease. METHODS: Twenty women
      with severe early onset preeclampsia before 24 weeks' gestation, who delivered
      between 1993-2003 in a tertiary referral centre and twenty matched controls with
      uncomplicated pregnancies and healthy term infants, were addressed for
      participation in the study. Venous plasma samples were analyzed for basic
      fibroblast growth factor (bFGF), placental growth factor (PLGF), soluble fms-like
      tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), E- and P
      selectin, soluble intercellular adhesion molecule-3 (sICAM-3) and thrombomodulin
      by ELISA. RESULTS: Sixteen case subjects and 18 control subjects consented
      participation. The median time interval index pregnancy to study was 9.4 and 9.7
      years for cases and controls, respectively. Median levels for cases-controls (p
      value) were not different; bFGF: 17.43-11.11 pg/mL (0.33), sFlt-1: 102.98-101.92
      pg/ml (0.84), PLGF: 3.57-4.20 pg/mL (0.38), VEGF: 64.05-45.72 pg/mL (0.73), E
      selectin: 5.11-4.68 ng/mL (0.20), P-selectin: 85.35-71.69 ng/mL (0.69), sICAM-3:
      0.42-0.63 ng/mL (0.41) and Thrombomodulin: 0.92-0.93 ng/mL (0.59). CONCLUSION:
      There were no differences in angiogenic biomarkers between women with a history
      of severe early onset preeclampsia versus uncomplicated pregnancy almost 10 years
      later, suggesting that these angiogenic factors will not contribute to the early
      detection of women at risk for future cardiovascular disease.

PMID- 22952729
TI  - Bronchoalveolar lavage results are independent of season, age, gender and
      collection site.
AB  - BACKGROUND: Clinical interpretation of bronchoalveolar lavage fluid results is
      dependent on the availability of reference values for healthy individuals. Only a
      few studies have published such reference values and the applicability of results
      is restricted by small sample sizes and the limited representativeness of the
      study population. We aim to investigate the influence of age, gender, collection
      site and season on bronchoalveolar lavage fluid results and to establish
      reference values for use in clinical practice. METHODOLOGY/PRINCIPAL FINDINGS:
      Bronchoalveolar lavage fluid data from 295 healthy never-smoking volunteers,
      investigated during 1990-2009, were analyzed retrospectively. 47 volunteers had 2
      5 repeat lavages during the course of several years. Fluid recovery, total number
      of cells, cell concentration, and differential cell counts on cytospin prepared
      slides were recorded. Reference values, as represented by the 5(th) to the 95(th)
      percentile, were 72-96% for macrophages, 2-26% for lymphocytes, 0-4% for
      neutrophils and 0-1% for eosinophils. Basophils and mast cells were rare. When
      repeat lavages were performed, there was a relatively large intra-individual
      variability, mainly for macrophages and lymphocytes. An age dependent decrease of
      lavage fluid return was present, but there was no age dependent correlation with
      any of the other BALF parameters. The BALF cell parameters were independent of
      gender, season and site (lingula vs. middle lobe). CONCLUSIONS/SIGNIFICANCE: Our
      data show that bronchoalveolar lavage fluid cell differential count is
      independent of age, gender, season and collection site (RML or lingua). It
      therefore seems acceptable to use the same reference values for all never-smoking
      individuals.

PMID- 22952730
TI  - Sequencing and de novo analysis of Crassostrea angulata (Fujian oyster) from 8
      different developing phases using 454 GSFlx.
AB  - Research on the mechanism for early development of shellfish, such as body plan,
      shell formation, settlement and metamorphosis is currently an active research
      field. However, studies were still limited and not deep enough because of the
      lack of genomic resources such as genome or transcriptome sequences. In the
      present research, de novo transcriptome sequencing was performed for Crassostrea
      angulata, the most economically important cultured oyster species in China, at
      eight early developmental stages using the 454 sequencing technology. A total of
      555,215 reads were produced with an average length of 309 nucleotides that were
      then assembled into 10,462 contigs. As determined by GO annotation and KEGG
      pathway mapping, functional annotation of the unigenes recovered diverse
      biological functions and processes. Six unique sequences related to settlement,
      metamorphosis and growth were subsequently analyzed by real-time PCR. Given the
      lack of whole genome information for oysters, transcriptome and de novo analysis
      of C. angulata from the eight different developing phases will provide important
      and useful information on early development mechanism and help genetic breeding
      of shellfish.

PMID- 22952731
TI  - Hemoglobin targets for chronic kidney disease patients with anemia: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Numerous studies have identified a relationship between hemoglobin
      (Hb) levels and mortality in patients with chronic kidney disease (CKD), which
      have raised concerns about the optimal Hb targets in correction of anemia. Our
      study is designed to investigate the potential effects of targeted Hb levels,
      aiming to give some evidence for therapy of renal anemia. METHODOLOGY/PRINCIPAL
      FINDINGS: A comprehensive search of Medline, Embase and the Cochrane Database of
      Systematic Reviews was performed in December 2011 and updated in February 2012
      for any new trials. Randomized trials designed to evaluate effects of high
      (generally the Hb about 13.0 g/dL) and low Hb (generally the Hb about 10.0 g/dL)
      targets on clinical outcomes in CKD patients with anemia were collected. All
      statistical analysis was calculated using the RevMan software available free from
      the Cochrane Collaboration. 24 trials involving 10361 patients were identified.
      Our findings demonstrated a statistically significant increased risk of mortality
      in the high Hb levels (RR 1.18; 95% CI 1.02 to 1.37) while the high and low Hb
      groups were both treated with ESAs. Overall, compared with low Hb levels, high Hb
      levels are associated with increased risk of hypertension (RR 1.40; 95% CI 1.11
      to 1.75), stroke (RR 1.73; 95% CI 1.31 to 2.29), and hospitalizations (RR 1.07;
      95% CI 1.01 to 1.14). However, there are no significant differences in the risk
      of non-fatal myocardial infarction (RR 1. 13; 95% CI 0.79 to 1.61) and renal
      replacement therapy (RR 1. 00; 95% CI 0.85 to 1.18). CONCLUSIONS/SIGNIFICANCES:
      Targeting low Hb levels are beneficial to CKD patients especially in the
      predialysis population. The optimal Hb targets to aim for in CKD patients and at
      what Hb level the risks of adverse events begin to increase remain elusive.
      Future studies are still needed to elucidate these questions.

PMID- 22952732
TI  - Distinct DNA methylation dynamics of spermatogenic cell-specific intronless genes
      is associated with CpG content.
AB  - In mammals, DNA methylation is restricted to cytosines of CpG dinucleotides,
      which are frequently found in short genomic regions including gene promoters.
      Methylation within CpG-rich regions around promoters tends to repress gene
      expression; thus, the CpG islands of housekeeping genes are normally
      unmethylated. We previously described a testis-specific single-exon gene
      containing a CpG-rich sequence that is methylated and thus repressed in somatic
      cells, whereas its expression in spermatogenic cells requires that it be
      hypomethylated. However, the relationship among the specific expression of
      spermatogenic genes, their methylation dynamics, and their CpG frequencies are
      poorly understood. Here, we analyzed the methylation patterns of the sphort
      genomic region around the transcription start site in spermatogenic cell-specific
      single-exon genes of various CpG contents. By using UniGene and Ensembl database
      analyses of the mouse genome and reverse transcription-PCR, we identified 39
      single-exon genes that are exclusively expressed in spermatogeniccells.
      Regardless of their specific expression characteristics, genes containing higher
      (7 to 14 CpGs in 200 bp; mean = 12) and lower (2 to 6 CpGs in 200 bp; mean = 3.1)
      number ofCpG were hypo- and hyper-methylated, respectively, in all cell types
      examined, including spermatogeniccells. We found that genes with intermediate
      number of CpG (2 to 11 CpGs in 200 bp; mean = 6.9) are methylated in somatic
      cells, but not in male germ cells. These results suggest that DNA methylation
      dynamics of spermatogenic cell-specific single-exon genes are associated with CpG
      content, and the methylation status are stably maintained throughout male germ
      cell development.

PMID- 22952733
TI  - Dynamic status of REST in the mouse ESC pluripotency network.
AB  - BACKGROUND: REST is abundantly expressed in mouse embryonic stem cells (ESCs).
      Many genome-wide analyses have found REST to be an integral part of the ESC
      pluripotency network. However, experimental systems have produced contradictory
      findings: (1) REST is required for the maintenance of ESC pluripotency and loss
      of REST causes increased expression of differentiation markers, (2) REST is not
      required for the maintenance of ESC pluripotency and loss of REST does not change
      expression of differentiation markers, and (3) REST is not required for the
      maintenance of ESC pluripotency but loss of REST causes decreased expression of
      differentiation markers. These reports highlight gaps in our knowledge of the ESC
      network. METHODS: Employing biochemical and genome-wide analyses of various
      culture conditions and ESC lines, we have attempted to resolve some of the
      discrepancies in the literature. RESULTS: We show that Rest+/- and Rest-/- AB-1
      mutant ESCs, which did not exhibit a role of REST in ESC pluripotency when
      cultured in the presence of feeder cells, did show impaired self-renewal when
      compared with the parental cells under feeder-free culture conditions, but only
      in early passage cells. In late passage cells, both Rest+/- and Rest-/- AB-1 ESCs
      restored pluripotency, suggesting a passage and culture condition-dependent
      response. Genome-wide analysis followed by biochemical validation supported this
      response and further indicated that the restoration of pluripotency was
      associated by increased expression of the ESC pluripotency factors. E14Tg2a.4
      ESCs with REST-knockdown, which earlier showed a REST-dependent pluripotency when
      cultured under feeder-free conditions, as well as Rest-/- AB-1 ESCs, showed no
      REST-dependent pluripotency when cultured in the presence of either feeder cells
      or laminin, indicating that extracellular matrix components can rescue REST's
      role in ESC pluripotency. CONCLUSIONS: REST regulates ESC pluripotency in culture
      condition- and ESC line-dependent fashion and ESC pluripotency needs to be
      evaluated in a context dependent manner.

PMID- 22952734
TI  - CD8 T cell epitope distribution in viruses reveals patterns of protein
      biosynthesis.
AB  - Distinguishing T cell epitope distribution patterns is relevant for epitope
      vaccine design. To that end, we invest0069gated the distribution of known CD8 T
      cell epitopes from Hepatitis C Virus, Human Immunodeficiency Virus-1 and
      Influenza A Virus using chi(2) statistics. We found that epitopes are not
      distributed in the viral proteomes proportionally to the size of the source
      proteins. Specifically, capsid and matrix proteins pack significantly more
      epitopes than those expected by their size. Such non-homogeneous distribution
      cannot be accounted by underlying MHC I-peptide binding preferences nor it is
      related to sequence variability. Instead, we propose that it might be related to
      preferential protein translation/biosynthesis. Overall, these results support the
      prioritization of structural antigens for epitope identification and vaccine
      design.

PMID- 22952735
TI  - Is metabolic flexibility altered in multiple sclerosis patients?
AB  - OBJECTIVES: Metabolic flexibility is defined as ability to adjust fuel oxidation
      to fuel availability. Multiple sclerosis (MS) results in reduced muscle strength
      and exercise intolerance. We tested the hypothesis that altered metabolic
      flexibility contributes to exercise intolerance in MS patients. METHODS: We
      studied 16 patients (all on glatiramer) and 16 matched healthy controls. Energy
      expenditure (EE), and carbohydrate (COX) and lipid oxidation (LOX) rates were
      determined by calorimetry, before and after an oral glucose load. We made
      measurements either at rest (canopy device) or during 40 min low-grade (0.5 W/kg)
      exercise (metabolic chamber). We also obtained plasma, and adipose tissue and
      skeletal muscle dialysate samples by microdialysis to study tissue-level
      metabolism under resting conditions. RESULTS: At rest, fasting and postprandial
      plasma glucose, insulin, and free fatty acid levels did not differ between
      patients and controls. Fasting and postprandial COX was higher and LOX lower in
      patients. In adipose, fasting and postprandial dialysate glucose, lactate, and
      glycerol levels were higher in patients vs. controls. In muscle, fasting and
      postprandial dialysate metabolite levels did not differ significantly between the
      groups. During exercise, EE did not differ between the groups. However, COX
      increased sharply over 20 min in patients, without reaching a steady state,
      followed by an immediate decrease within the next 20 min and fell even below
      basal levels after exercise in patients, compared to controls. CONCLUSIONS:
      Glucose tolerance is not impaired in MS patients. At rest, there is no indication
      for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The
      increased adipose tissue lipolytic activity might result from glatiramer
      treatment. Autonomic dysfunction might cause dysregulation of postprandial
      thermogenesis at rest and lipid mobilization during exercise.

PMID- 22952736
TI  - Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice.
AB  - Stroke represents an attractive target for stem cell therapy. Although different
      types of cells have been employed in animal models, a direct comparison between
      cell sources has not been performed. The aim of our study was to assess the
      effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal
      stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation
      following stroke. BALB/Ca-RAG 2(-/-) gammaC(-/-) mice subjected to FeCl(3)
      thrombosis mediated stroke were intracranially injected with 2 * 10(5) hMAPCs or
      hMSCs 2 days after stroke and followed for up to 28 days. We could not detect
      long-term engraftment of either cell population. However, in comparison with PBS
      treated animals, hMSC and hMAPC grafted animals demonstrated significantly
      decreased loss of brain tissue. This was associated with increased angiogenesis,
      diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced
      proliferation of cells in the subventricular zone (SVZ) and survival of newly
      generated neuroblasts was observed. Interestingly, these neuroprotective effects
      were more pronounced in the group of animals treated with hMAPCs in comparison
      with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a
      promising strategy for the treatment of stroke.

PMID- 22952737
TI  - Pharmacokinetics of peptide mediated delivery of anticancer drug ellipticine.
AB  - The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize
      the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this
      study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in
      vivo. The developed formulation can achieve a sufficiently high drug
      concentration required in vivo animal models. The nanostructure and surface
      properties of EAK-EPT complexes or nanoparticle were characterized by
      transmission electron microscopy (TEM) and zeta potential measurements,
      respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT
      group randomly. Rats in EPT group were tail intravenously injected with the EPT
      (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's
      concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone
      sodium phosphate as internal standards (IS). The pharmacokinetic parameters were
      obtained using high pressure liquid chromatography (HPLC). Significant
      differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes
      were observed, demonstrating that the complexation with EAK prolongs the
      residence time of the drug and enlarges the area under the concentration-time
      curve (AUC). This means that EAK can serve as a suitable carrier to increase the
      bioavailability of EPT.

PMID- 22952738
TI  - 17beta-estradiol regulates the sexually dimorphic expression of BDNF and TrkB
      proteins in the song system of juvenile zebra finches.
AB  - Mature brain derived neurotrophic factor (BDNF) plays critical roles in
      development of brain structure and function, including neurogenesis, axon growth,
      cell survival and processes associated with learning. Expression of this peptide
      is regulated by estradiol (E2). The zebra finch song system is sexually dimorphic
      - only males sing and the brain regions controlling song are larger and have more
      cells in males compared to females. Masculinization of this system is partially
      mediated by E2, and earlier work suggests that BDNF with its high affinity
      receptor TrkB may also influence this development. The present study evaluated
      expression of multiple forms of both BDNF and TrkB in the developing song system
      in juvenile males and females treated with E2 or a vehicle control. Using
      immunohistochemistry and Western blot analysis, BDNF was detected across the song
      nuclei of 25-day-old birds. Westerns allowed the pro- and mature forms of BDNF to
      be individually identified, and proBDNF to be quantified. Several statistically
      significant effects of sex existed in both the estimated total number of BDNF+
      cells and relative concentration of proBDNF, varying across the regions and
      methodologies. E2 modulated BDNF expression, although the specific nature of the
      regulation depended on brain region, sex and the technique used. Similarly, TrkB
      (both truncated and full-length isoforms) was detected by Western blot in the
      song system of juveniles of both sexes, and expression was regulated by E2. In
      the context of earlier research on these molecules in the developing song system,
      this work provides a critical step in describing specific forms of BDNF and TrkB,
      and how they can be mediated by sex and E2. As individual isoforms of each can
      have opposing effects on mechanisms, such as cell survival, it will now be
      important to investigate in depth their specific functions in song system
      maturation.

PMID- 22952739
TI  - Identification and analysis of the putative pentose sugar efflux transporters in
      Escherichia coli.
AB  - Escherichia coli possesses a number of proteins that transport sugars out of the
      cell. We identified 31 candidate sugar efflux transporters based on their
      similarity to known sugar efflux transporters. We then tested whether these
      transporters affect arabinose and xylose metabolism. We identified 13
      transporters - setC, cmr, ynfM, mdtD, yfcJ, yhhS, emrD, ydhC, ydeA, ybdA, ydeE,
      mhpT, and kgtP - that appeared to increase or decrease intracellular arabinose
      concentrations when respectively deleted or over-expressed. None of the candidate
      transporters affected xylose concentrations. These results indicate that E. coli
      possesses multiple arabinose efflux transporters. They also provide a novel
      target for future metabolic engineering.

PMID- 22952741
TI  - Conic sampling: an efficient method for solving linear and quadratic programming
      by randomly linking constraints within the interior.
AB  - Linear programming (LP) problems are commonly used in analysis and resource
      allocation, frequently surfacing as approximations to more difficult problems.
      Existing approaches to LP have been dominated by a small group of methods, and
      randomized algorithms have not enjoyed popularity in practice. This paper
      introduces a novel randomized method of solving LP problems by moving along the
      facets and within the interior of the polytope along rays randomly sampled from
      the polyhedral cones defined by the bounding constraints. This conic sampling
      method is then applied to randomly sampled LPs, and its runtime performance is
      shown to compare favorably to the simplex and primal affine-scaling algorithms,
      especially on polytopes with certain characteristics. The conic sampling method
      is then adapted and applied to solve a certain quadratic program, which compute a
      projection onto a polytope; the proposed method is shown to outperform the
      proprietary software Mathematica on large, sparse QP problems constructed from
      mass spectometry-based proteomics.

PMID- 22952740
TI  - Neutralization of tier-2 viruses and epitope profiling of plasma antibodies from
      human immunodeficiency virus type 1 infected donors from India.
AB  - Broadly cross neutralizing antibodies (NAbs) are generated in a group of HIV-1
      infected individuals during the natural infection, but little is known about
      their prevalence in patients infected with viral subtypes from different
      geographical regions. We tested here the neutralizing efficiency of plasma
      antibodies from 80 HIV-1 infected antiretroviral drug naive patients against a
      panel of subtype-B and C tier 2 viruses. We detected cross-neutralizing
      antibodies in approximately 19-27% of the plasma, however the subtype-C specific
      neutralization efficiency predominated (p = 0.004). The neutralizing activity was
      shown to be exclusively mediated by the immunoglobulin G (IgG) fraction in the
      representative plasma samples. Epitope mapping of three, the most cross
      neutralizing plasma (CNP) AIIMS206, AIIMS239 and AIIMS249 with consensus-C
      overlapping envelope peptides revealed ten different binding specificities with
      only V3 and IDR being common. The V3 and IDR were highly antigenic regions but no
      correlation between their reciprocal Max50 binding titers and neutralization was
      observed. In addition, the neutralizing activity of CNP was not substantially
      reduced by V3 and gp41 peptides except a modest contribution of MPER peptide. The
      MPER was rarely recognized by plasma antibodies though antibody depletion and
      competition experiments demonstrated MPER dependent neutralization in two out of
      three CNP. Interestingly, the binding specificity of one of the CNP (AIIMS206)
      overlapped with broadly neutralizing mAb 2F5 epitope. Overall, the data suggest
      that, despite the low immunogenicity of HIV-1 MPER, the antibodies directed to
      this region may serve as crucial reagents for HIV-1 vaccine design.

PMID- 22952742
TI  - Endogenous fluorescence signatures in living pluripotent stem cells change with
      loss of potency.
AB  - The therapeutic potential of stem cells is limited by the non-uniformity of their
      phenotypic state. Thus it would be advantageous to noninvasively monitor stem
      cell status. Driven by this challenge, we employed multidimensional multiphoton
      microscopy to quantify changes in endogenous fluorescence occurring with
      pluripotent stem cell differentiation. We found that global and cellular-scale
      fluorescence lifetime of human embryonic stem cells (hESC) and murine embryonic
      stem cells (mESC) consistently decreased with differentiation. Less consistent
      were trends in endogenous fluorescence intensity with differentiation, suggesting
      intensity is more readily impacted by nuances of species and scale of analysis.
      What emerges is a practical and accessible approach to evaluate, and ultimately
      enrich, living stem cell populations based on changes in metabolism that could be
      exploited for both research and clinical applications.

PMID- 22952743
TI  - LPS-induced lung inflammation in marmoset monkeys - an acute model for anti
      inflammatory drug testing.
AB  - Increasing incidence and substantial morbidity and mortality of respiratory
      diseases requires the development of new human-specific anti-inflammatory and
      disease-modifying therapeutics. Therefore, new predictive animal models that
      closely reflect human lung pathology are needed. In the current study, a tiered
      acute lipopolysaccharide (LPS)-induced inflammation model was established in
      marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory
      lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of
      comparison, human precision-cut lung slices (PCLS) were stimulated with LPS in
      the presence or absence of the phosphodiesterase-4 (PDE4) inhibitor roflumilast.
      Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and
      macrophage inflammatory protein-1 beta (MIP-1beta) were measured. The
      corticosteroid dexamethasone was used as treatment control. Secondly, in an in
      vivo approach marmosets were pre-treated with roflumilast or dexamethasone and
      unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL) was
      conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for
      neutrophils, TNF-alpha, and MIP-1beta. TNF-alpha release in marmoset PCLS
      correlated significantly with human PCLS. Roflumilast treatment significantly
      reduced TNF-alpha secretion ex vivo in both species, with comparable half maximal
      inhibitory concentration (IC(50)). LPS instillation into marmoset lungs caused a
      profound inflammation as shown by neutrophilic influx and increased TNF-alpha and
      MIP-1beta levels in BAL fluid. This inflammatory response was significantly
      suppressed by roflumilast and dexamethasone. The close similarity of marmoset and
      human lungs regarding LPS-induced inflammation and the significant anti
      inflammatory effect of approved pharmaceuticals assess the suitability of
      marmoset monkeys to serve as a promising model for studying anti-inflammatory
      drugs.

PMID- 22952744
TI  - Global projections of 21st century land-use changes in regions adjacent to
      Protected Areas.
AB  - The conservation efficiency of Protected Areas (PA) is influenced by the health
      and characteristics of the surrounding landscape matrix. Fragmentation of
      adjacent lands interrupts ecological flows within PAs and will decrease the
      ability of species to shift their distribution as climate changes. For five
      periods across the 21(st) century, we assessed changes to the extent of primary
      land, secondary land, pasture and crop land projected to occur within 50 km
      buffers surrounding IUCN-designated PAs. Four scenarios of land-use were obtained
      from the Land-Use Harmonization Project, developed for the Intergovernmental
      Panel on Climate Change's Fifth Assessment Report (AR5). The scenarios project
      the continued decline of primary lands within buffers surrounding PAs.
      Substantial losses are projected to occur across buffer regions in the tropical
      forest biomes of Indo-Malayan and the Temperate Broadleaf forests of the
      Nearctic. A number of buffer regions are projected to have negligible primary
      land remaining by 2100, including those in the Afrotropic's Tropical/Subtropical
      Grassland/Savanna/Shrubland. From 2010-2050, secondary land is projected to
      increase within most buffer regions, although, as with pasture and crops within
      tropical and temperate forests, projections from the four land-use scenarios may
      diverge substantially in magnitude and direction of change. These scenarios
      demonstrate a range of alternate futures, and show that although effective
      mitigation strategies may reduce pressure on land surrounding PAs, these areas
      will contain an increasingly heterogeneous matrix of primary and human-modified
      landscapes. Successful management of buffer regions will be imperative to ensure
      effectiveness of PAs and to facilitate climate-induced shifts in species ranges.

PMID- 22952745
TI  - Severe heat shock induces nucleolar accumulation of mRNAs in Trypanosoma cruzi.
AB  - Several lines of evidence have shown that, besides its traditional function in
      ribosome biogenesis, the nucleolus is also involved in regulating other cellular
      processes such as mRNA metabolism, and that it also plays an important role as a
      sensor and coordinator of the stress response. We have recently shown that a
      subset of RNA Binding Proteins and the poly(A)+ RNA are accumulated into the
      Trypanosoma cruzi nucleolus after inducing transcription inhibition with
      Actinomycin D. In this study, we investigated the behaviour of the T. cruzi mRNA
      population in parasites subjected to severe heat shock, an environmental stress
      that also decreases the rate of RNA synthesis. We found that the bulk of poly(A)+
      RNA is reversibly accumulated into the nucleolus when exposing T. cruzi
      epimastigote forms to severe heat shock. However, the Hsp70 mRNA was able to
      bypass such nucleolar accumulation. Together, these data reinforce the idea about
      the involvement of the T. cruzi nucleolus in mRNA metabolism during an
      environmental stress response. Interestingly, T. brucei procyclic forms did not
      induce nucleolar accumulation of poly(A)+ RNA under such stress condition,
      suggesting that different trypanosomatids have adopted different responses to
      deal with the same stress conditions.

PMID- 22952746
TI  - Genetic diversity and population structure of Indian golden silkmoth (Antheraea
      assama).
AB  - BACKGROUND: The Indian golden saturniid silkmoth (Antheraea assama), popularly
      known as muga silkmoth, is a semi-domesticated silk producing insect confined to
      a narrow habitat range of the northeastern region of India. Owing to the
      prevailing socio-political problems, the muga silkworm habitats in the
      northeastern region have not been accessible hampering the phylogeography studies
      of this rare silkmoth. Recently, we have been successful in our attempt to
      collect muga cocoon samples, although to a limited extent, from their natural
      habitats. Out of 87 microsatellite markers developed previously for A. assama, 13
      informative markers were employed to genotype 97 individuals from six populations
      and analyzed their population structure and genetic variation.
      METHODOLOGY/PRINCIPAL FINDINGS: We observed highly significant genetic diversity
      in one of the populations (WWS-1, a population derived from West Garo Hills
      region of Meghalaya state). Further analysis with and without WWS-1 population
      revealed that dramatic genetic differentiation (global F(ST) = 0.301) was due to
      high genetic diversity contributed by WWS-1 population. Analysis of the remaining
      five populations (excluding WWS-1) showed a marked reduction in the number of
      alleles at all the employed loci. Structure analysis showed the presence of only
      two clusters: one formed by WWS-1 population and the other included the remaining
      five populations, inferring that there is no significant genetic diversity within
      and between these five populations, and suggesting that these five populations
      are probably derived from a single population. Patterns of recent population
      bottlenecks were not evident in any of the six populations studied.
      CONCLUSIONS/SIGNIFICANCE: A. assama inhabiting the WWS-1 region revealed very
      high genetic diversity, and was genetically divergent from the five populations
      studied. The efforts should be continued to identify and study such populations
      from this region as well as other muga silkworm habitats. The information
      generated will be very useful in conservation of dwindling muga culture in
      Northeast India.

PMID- 22952747
TI  - Inferring multiple refugia and phylogeographical patterns in Pinus massoniana
      based on nucleotide sequence variation and DNA fingerprinting.
AB  - BACKGROUND: Pinus massoniana, an ecologically and economically important conifer,
      is widespread across central and southern mainland China and Taiwan. In this
      study, we tested the central-marginal paradigm that predicts that the marginal
      populations tend to be less polymorphic than the central ones in their genetic
      composition, and examined a founders' effect in the island population.
      METHODOLOGY/PRINCIPAL FINDINGS: We examined the phylogeography and population
      structuring of the P. massoniana based on nucleotide sequences of cpDNA atpB-rbcL
      intergenic spacer, intron regions of the AdhC2 locus, and microsatellite
      fingerprints. SAMOVA analysis of nucleotide sequences indicated that most genetic
      variants resided among geographical regions. High levels of genetic diversity in
      the marginal populations in the south region, a pattern seemingly contradicting
      the central-marginal paradigm, and the fixation of private haplotypes in most
      populations indicate that multiple refugia may have existed over the glacial
      maxima. STRUCTURE analyses on microsatellites revealed that genetic structure of
      mainland populations was mediated with recent genetic exchanges mostly via pollen
      flow, and that the genetic composition in east region was intermixed between
      south and west regions, a pattern likely shaped by gene introgression and
      maintenance of ancestral polymorphisms. As expected, the small island population
      in Taiwan was genetically differentiated from mainland populations.
      CONCLUSIONS/SIGNIFICANCE: The marginal populations in south region possessed
      divergent gene pools, suggesting that the past glaciations might have low impacts
      on these populations at low latitudes. Estimates of ancestral population sizes
      interestingly reflect a recent expansion in mainland from a rather smaller
      population, a pattern that seemingly agrees with the pollen record.

PMID- 22952748
TI  - The small heat shock protein p26 aids development of encysting Artemia embryos,
      prevents spontaneous diapause termination and protects against stress.
AB  - Artemia franciscana embryos enter diapause as encysted gastrulae, a physiological
      state of metabolic dormancy and enhanced stress resistance. The objective of this
      study was to use RNAi to investigate the function of p26, an abundant, diapause
      specific small heat shock protein, in the development and behavior of encysted
      Artemia embryos (cysts). RNAi methodology was developed where injection of
      Artemia females with dsRNA specifically eliminated p26 from cysts. p26 mRNA and
      protein knock down were, respectively, confirmed by RT-PCR and immuno-probing of
      western blots. ArHsp21 and ArHsp22, diapause-related small heat shock proteins in
      Artemia cysts sharing a conserved alpha-crystallin domain with p26, were
      unaffected by injection of females with dsRNA for p26, demonstrating the
      specificity of protein knock down. Elimination of p26 delayed cyst release from
      females demonstrating that this molecular chaperone influences the development of
      diapause-destined embryos. Although development was slowed the metabolic
      activities of cysts either containing or lacking p26 were similar. p26 inhibited
      diapause termination after prolonged incubation of cysts in sea water perhaps by
      a direct effect on termination or indirectly because p26 is necessary for the
      preservation of diapause maintenance. Cyst diapause was however, terminated by
      desiccation and freezing, a procedure leading to high mortality within cyst
      populations lacking p26 and indicating the protein is required for stress
      tolerance. Cysts lacking p26 were also less resistant to heat shock. This is the
      first in vivo study to show that knock down of a small heat shock protein slows
      the development of diapause-destined embryos, suggesting a role for p26 in the
      developmental process. The same small heat shock protein prevents spontaneous
      termination of diapause and provides stress protection to encysted embryos.

PMID- 22952750
TI  - Association of SNP rs6903956 on chromosome 6p24.1 with angiographical
      characteristics of coronary atherosclerosis in a Chinese population.
AB  - OBJECTIVE: To explore the association between rs6903956 and severity of coronary
      artery disease (CAD) in a Chinese population. METHODS: A cohort of 1075
      consecutive patients who underwent coronary arteriography for suspected or known
      coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis
      severity was defined by Gensini's Score System and counts of diseased vessels.
      RESULTS: Gensini score frequencies and counts of diseased vessels differed among
      GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score
      frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A
      univariate logistic regression analysis revealed that the genotype distribution
      of this SNP was associated significantly with angiographical characteristics of
      coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence
      interval (CI) = 1.036~2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI =
      1.299~26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132~2.162 for
      combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated
      that the genotype distribution of the rs6903956 polymorphism be associated
      significantly with the angiographical characteristics of coronary atherosclerosis
      risk (p = 0.004, OR = 1.578, 95% CI = 1.155~2.154 for GG vs. AG vs. AA; p =
      0.013, OR = 1.541, 95% CI = 1.097~2.163 for GG vs. GA+ AA). A stratification
      analysis revealed that male subjects and smoking subjects had a higher frequency
      of the rs6903956 heterozygous mutant among higher Gensini score subjects than
      among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064~2.344
      for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249~3.448 for smoking
      subgroup). CONCLUSIONS: Allele A is a risk factor for CAD and the G-to-A allele
      substitution may underlie the association between rs6903956 and CAD.

PMID- 22952749
TI  - Hypoxia induced aggressiveness of prostate cancer cells is linked with
      deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF.
AB  - Tumor hypoxia with deregulated expression of hypoxia inducing factor (HIF) and
      its biological consequence leads to poor prognosis of patients diagnosed with
      solid tumors, resulting in higher mortality, suggesting that understanding of the
      molecular relationship of hypoxia with other cellular features of tumor
      aggressiveness would be invaluable for developing newer targeted therapy for
      solid tumors. Emerging evidence also suggest that hypoxia and HIF signaling
      pathways contributes to the acquisition of epithelial-to-mesenchymal transition
      (EMT), maintenance of cancer stem cell (CSC) functions, and also maintains the
      vicious cycle of inflammation, all of which contribute to radiation therapy and
      chemotherapy resistance. However, the detailed mechanisms by which hypoxia/HIF
      drive these events are not fully understood. Here, we have shown that hypoxia
      leads to increased expression of VEGF, IL-6, and CSC marker genes such as Nanog,
      Oct4 and EZH2, and also increased the expression of miR-21, an oncogenic miRNA,
      in prostate cancer (PCa) cells (PC-3 and LNCaP). The treatment of PCa cells with
      CDF, a novel Curcumin-derived synthetic analogue previously showed anti-tumor
      activity in vivo, inhibited the productions of VEGF and IL-6, and down-regulated
      the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 under hypoxic
      condition. Moreover, CDF treatment of PCa cells led to decreased cell migration
      under hypoxic condition. Taken together, these results suggest that the anti
      tumor effect of CDF is in part mediated through deregulation of tumor hypoxic
      pathways, and thus CDF could become useful for cancer therapy.

PMID- 22952751
TI  - I-PfoP3I: a novel nicking HNH homing endonuclease encoded in the group I intron
      of the DNA polymerase gene in Phormidium foveolarum phage Pf-WMP3.
AB  - Homing endonucleases encoded in a group I self-splicing intron in a protein
      coding gene in cyanophage genomes have not been reported, apart from some free
      standing homing edonucleases. In this study, a nicking DNA endonuclease, I
      PfoP3I, encoded in a group IA2 intron in the DNA polymerase gene of a T7-like
      cyanophage Pf-WMP3, which infects the freshwater cyanobacterium Phormidium
      foveolarum is described. The Pf-WMP3 intron splices efficiently in vivo and self
      splices in vitro simultaneously during transcription. I-PfoP3I belongs to the HNH
      family with an unconventional C-terminal HNH motif. I-PfoP3I nicks the intron
      minus Pf-WMP3 DNA polymerase gene more efficiently than the Pf-WMP4 DNA
      polymerase gene that lacks any intervening sequence in vitro, indicating the
      variable capacity of I-PfoP3I. I-PfoP3I cleaves 4 nt upstream of the intron
      insertion site on the coding strand of EXON 1 on both intron-minus Pf-WMP3 and Pf
      WMP4 DNA polymerase genes. Using an in vitro cleavage assay and scanning deletion
      mutants of the intronless target site, the minimal recognition site was
      determined to be a 14 bp region downstream of the cut site. I-PfoP3I requires
      Mg(2+), Ca(2+) or Mn(2+) for nicking activity. Phylogenetic analysis suggests
      that the intron and homing endonuclease gene elements might be inserted in Pf
      WMP3 genome individually after differentiation from Pf-WMP4. To our knowledge,
      this is the first report of the presence of a group I self-splicing intron
      encoding a functional homing endonuclease in a protein-coding gene in a
      cyanophage genome.

PMID- 22952752
TI  - Molecular evolutionary analysis of pH1N1 2009 influenza virus in Reunion Island,
      South West Indian Ocean region: a cohort study.
AB  - BACKGROUND/OBJECTIVES: Molecular epidemiology is a powerful tool to decipher the
      dynamics of viral transmission, quasispecies temporal evolution and origins.
      Little is known about the pH1N1 molecular dynamics in general population. A
      prospective study (CoPanFlu-RUN) was carried out in Reunion Island to
      characterize pH1N1 genetic variability and molecular evolution occurring in
      population during the pH1N1 Influenza pandemic in 2009. METHODOLOGY: We directly
      amplified pH1N1 genomes from 28 different nasal swabs (26 individuals from 21
      households). Fifteen strains were fully sequenced and 13 partially. This includes
      pairs of sequences from different members of 5 separate households; and two pairs
      from individuals, collected at different times. We assessed the molecular
      evolution of pH1N1 by genetic variability and phylogenetic analyses. PRINCIPAL
      FINDINGS: We found that i) Reunion pH1N1 sequences stemmed from global "clade 7"
      but shaped two phylogenetic sub-clades; ii) D239E mutation was identified in the
      hemagglutinin protein of all Reunion sequences, a mutation which has been
      associated elsewhere with mild-, upper-respiratory tract pH1N1 infecting strains;
      iii) Date estimates from molecular phylogenies predicted clade emergence some
      time before the first detection of pH1N1 by the epidemiological surveillance
      system; iv) Phylogenetic relatedness was observed between Reunion pH1N1 viruses
      and those from other countries in South-western Indian Ocean area; v)
      Quasispecies populations were observed within households and individuals of the
      cohort-study. CONCLUSIONS: Surveillance and/or prevention systems presently based
      on Influenza virus sequence variation should take into account that the majority
      of studies of pH1N1 Influenza generate genetic data for the HA/NA viral segments
      obtained from hospitalized-patients, which is potentially non-representative of
      the overall viral diversity within whole populations. Our observations highlight
      the importance of collecting unbiased data at the community level and conducting
      whole genome analysis to accurately understand viral dynamics.

PMID- 22952753
TI  - Temperament and hunger interact to determine the emergence of leaders in pairs of
      foraging fish.
AB  - Studies on leadership have focused either on physiological state as the key
      predictor (i.e. "leading according to need"), or else on temperamental
      asymmetries among group members (i.e. intrinsic leadership). In this paper, we
      explore how both factors interact in determining the emergence of leaders. We
      observed pairs of sticklebacks with varying degrees of temperamental difference,
      and recorded their movements back and forth between a safe covered area and a
      risky foraging area, both before and after satiating one of the two pair members
      (but not the other). Before satiation, when the fish had similar hunger levels,
      temperament was a good predictor of social roles, with the bolder member of a
      pair leading and the shyer member following. The effect of satiation depended on
      which fish received the additional food. When the shyer member of a pair was fed,
      and consequently became less active, the bolder fish did not change its behaviour
      but continued to lead. By contrast, when the bolder member of a pair was fed, and
      consequently initiated fewer trips out of cover, the shyer partner compensated by
      initiating trips more frequently itself. In pairs that differed only a little in
      temperament, feeding the bolder fish actually led to a role reversal, with the
      shyer fish emerging as a leader in the majority of joint trips out of cover. Our
      results show that leadership emerges as the consequence of multiple factors, and
      that their interaction can be complex.

PMID- 22952754
TI  - Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis
      for the prevention of mother-to-child transmission of HIV.
AB  - BACKGROUND: We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT
      prophylaxis in a multi-country HIV care program. METHODS: Analysis was restricted
      to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+
      >=250 cells/mm(3) at enrollment. Single-dose nevirapine (sd-NVP) or short-course
      antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine
      (3TC) was initiated in 11 programs while 2 programs offered triple-drug
      antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens
      were stopped at delivery. CD4+ decline was defined as proportion of women who
      declined to CD4+ <350 cells/mm(3) or <200 cells/mm(3) at 24 months. Weibull
      regression was used for multivariable analysis. FINDINGS: A total of 1,393 women
      with enrollment CD4+ >=250 cells/mm(3) initiated tARVp (172; 12%) or sc-ARVp
      (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At
      enrollment, maternal median age was 27 years (interquartile range (IQR) 23-30),
      median CD4+ was 469 cells/mm(3) (IQR: 363-613). At 24 months post-delivery, the
      cumulative probability of CD4+ decline to <200 cells/mm(3) was 12% (95% CI: 10
      14). Among a subgroup of 903 women with CD4+ >=400 cells at enrollment, the 24
      month cumulative probability of decline to CD4+ <350 cells/mm(3) was 28%; (95%
      CI: 25-32). Lower antepartum CD4+ was associated with higher probability of CD4+
      decline to <350 cells/mm(3): 46% (CD4+400-499 cells/mm(3)) vs. 19% (CD4+ >=500
      cells/mm(3)). After adjusting for age, enrollment CD4+ and WHO stage, women who
      received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350
      cells/mm(3) within 24 months than women receiving sc-ARVp (adjusted hazard ratio:
      2.2; 95% CI: 1.5-3.2, p<0.0001). CONCLUSION: Decline in CD4+ cell count to ART
      eligibility thresholds by 24 months postpartum was common among women receiving
      PMTCT prophylaxis during pregnancy and/or delivery.

PMID- 22952755
TI  - CD146 expression in human breast cancer cell lines induces phenotypic and
      functional changes observed in Epithelial to Mesenchymal Transition.
AB  - BACKGROUND: Metastasis is an important step in tumor progression leading to a
      disseminated and often incurable disease. First steps of metastasis include down
      regulation of cell adhesion molecules, alteration of cell polarity and
      reorganization of cytoskeleton, modifications associated with enhanced migratory
      properties and resistance of tumor cells to anoikis. Such modifications resemble
      Epithelial to Mesenchymal Transition (EMT). In breast cancer CD146 expression is
      associated with poor prognosis and enhanced motility. METHODOLOGY/PRINCIPAL
      FINDINGS: On 4 different human breast cancer cell lines, we modified CD146
      expression either with shRNA technology in CD146 positive cells or with stable
      transfection of CD146 in negative cells. Modifications in morphology, growth and
      migration were evaluated. Using Q-RT-PCR, we analyzed the expression of different
      EMT markers. We demonstrate that high levels of CD146 are associated with loss of
      cell-cell contacts, expression of EMT markers, increased cell motility and
      increased resistance to doxorubicin or docetaxel. Experimental modulation of
      CD146 expression induces changes consistent with the above described
      characteristics: morphology, motility, growth in anchorage independent conditions
      and Slug mRNA variations are strictly correlated with CD146 expression. These
      changes are associated with modifications of ER (estrogen receptor) and Erb
      receptors and are enhanced by simultaneous and opposite modulation of JAM-A, or
      exposure to heregulin, an erb-B4 ligand. CONCLUSIONS: CD146 expression is
      associated with an EMT phenotype. Several molecules are affected by CD146
      expression: direct or indirect signaling contributes to EMT by increasing Slug
      expression. CD146 may also interact with Erb signaling by modifying cell surface
      expression of ErbB3 and ErbB4 and increased resistance to chemotherapy.
      Antagonistic effects of JAM-A, a tight junction-associated protein, on CD146
      promigratory effects underline the complexity of the adhesion molecules network
      in tumor cell migration and metastasis.

PMID- 22952757
TI  - Human apolipoprotein A-I natural variants: molecular mechanisms underlying
      amyloidogenic propensity.
AB  - Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either
      wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary
      form in which apoA-I variants deposit causing multiple organ failure. More than
      15 single amino acid replacement amyloidogenic apoA-I variants have been
      described, but the molecular mechanisms involved in amyloid-associated pathology
      remain largely unknown. Here, we have investigated by fluorescence and
      biochemical approaches the stabilities and propensities to aggregate of two
      disease-associated apoA-I variants, apoA-IGly26Arg, associated with
      polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in
      amyloidosis in severe atherosclerosis. Results showed that both variants share
      common structural properties including decreased stability compared to Wt apoA-I
      and a more flexible structure that gives rise to formation of partially folded
      states. Interestingly, however, distinct features appear to determine their
      pathogenic mechanisms. ApoA-ILys107-0 has an increased propensity to aggregate at
      physiological pH and in a pro-inflammatory microenvironment than Wt apoA-I,
      whereas apoA-IGly26Arg elicited macrophage activation, thus stimulating local
      chronic inflammation. Our results strongly suggest that some natural mutations in
      apoA-I variants elicit protein tendency to aggregate, but in addition the
      specific interaction of different variants with macrophages may contribute to
      cellular stress and toxicity in hereditary amyloidosis.

PMID- 22952758
TI  - Comparative transcript profiling of a male sterile cybrid pummelo and its fertile
      type revealed altered gene expression related to flower development.
AB  - Male sterile and seedless characters are highly desired for citrus cultivar
      improvement. In our breeding program, a male sterile cybrid pummelo, which could
      be considered as a variant of male fertile pummelo, was produced by protoplast
      fusion. Herein, ecotopic stamen primordia initiation and development were
      detected in this male sterile cybrid pummelo. Histological studies revealed that
      the cybrid showed reduced petal development in size and width, and retarded
      stamen primordia development. Additionally, disorganized cell proliferation was
      also detected in stamen-like structures (fused to petals and/or carpel). To gain
      new insight into the underlying mechanism, we compared, by RNA-Seq analysis, the
      nuclear gene expression profiles of floral buds of the cybrid with that of
      fertile pummelo. Gene expression profiles which identified a large number of
      differentially expressed genes (DEGs) between the two lines were captured at both
      petal primordia and stamen primordia distinguishable stages. For example, nuclear
      genes involved in nucleic acid binding and response to hormone synthesis and
      metabolism, genes required for floral bud identification and expressed in
      particular floral whorls. Furthermore, in accordance with flower morphology of
      the cybrid, expression of PISTILLATA (PI) was reduced in stamen-like structures,
      even though it was restricted to correct floral whorls. Down-regulated expression
      of APETALA3 (AP3) coincided with that of PI. These finding indicated that, due to
      their whorl specific effects in flower development, citrus class-B MADS-box genes
      likely constituted 'perfect targets' for CMS retrograde signaling, and that
      dysfunctional mitochondria seemed to cause male sterile phenotype in the cybrid
      pummelo.

PMID- 22952759
TI  - Identification and comparative profiling of miRNAs in an early flowering mutant
      of trifoliate orange and its wild type by genome-wide deep sequencing.
AB  - MicroRNAs (miRNAs) are a new class of small, endogenous RNAs that play a
      regulatory role in various biological and metabolic processes by negatively
      affecting gene expression at the post-transcriptional level. While the number of
      known Arabidopsis and rice miRNAs is continuously increasing, information
      regarding miRNAs from woody plants such as citrus remains limited. Solexa
      sequencing was performed at different developmental stages on both an early
      flowering mutant of trifoliate orange (precocious trifoliate orange, Poncirus
      trifoliata L. Raf.) and its wild-type in this study, resulting in the obtainment
      of 141 known miRNAs belonging to 99 families and 75 novel miRNAs in four
      libraries. A total of 317 potential target genes were predicted based on the 51
      novel miRNAs families, GO and KEGG annotation revealed that high ranked miRNA
      target genes are those implicated in diverse cellular processes in plants,
      including development, transcription, protein degradation and cross adaptation.
      To characterize those miRNAs expressed at the juvenile and adult development
      stages of the mutant and its wild-type, further analysis on the expression
      profiles of several miRNAs through real-time PCR was performed. The results
      revealed that most miRNAs were down-regulated at adult stage compared with
      juvenile stage for both the mutant and its wild-type. These results indicate that
      both conserved and novel miRNAs may play important roles in citrus growth and
      development, stress responses and other physiological processes.

PMID- 22952760
TI  - Preservation of metabolic flexibility in skeletal muscle by a combined use of n-3
      PUFA and rosiglitazone in dietary obese mice.
AB  - Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a
      low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic
      inflexibility. This, in turn, contributes to a further damage of insulin
      signaling. Effectiveness of T2D treatment depends in large part on the
      improvement of insulin sensitivity and metabolic adaptability of the muscle, the
      main site of whole-body glucose utilization. We have shown previously in mice fed
      an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated
      fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs,
      preserved metabolic health and synergistically improved muscle insulin
      sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive
      beneficial effects on metabolic flexibility when combined with a TZD drug
      rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based
      high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions:
      cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF
      with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect
      calorimetry demonstrated superior preservation of metabolic flexibility to
      carbohydrates in response to the combined intervention. Metabolomic and gene
      expression analyses in the muscle suggested distinct and complementary effects of
      the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids
      in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting
      insulin sensitivity by the modulation of branched-chain amino acid metabolism.
      These beneficial metabolic effects were associated with the activation of the
      switch between glycolytic and oxidative muscle fibers, especially in the
      cHF+F+ROSI mice. Our results further support the idea that the combined use of n
      3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and
      diabetic patients.

PMID- 22952761
TI  - A method for rapid and simultaneous mapping of genetic loci and introgression
      sizes in nematode species.
AB  - Caenorhabditis briggsae is emerging as an attractive model organism not only in
      studying comparative biology against C. elegans, but also in developing novel
      experimentation avenues. In particular, recent identification of a new
      Caenorhabditis species, C. sp.9 with which it can mate and produce viable progeny
      provides an opportunity for studying the genetics of hybrid incompatibilities
      (HI) between the two. Mapping of a specific HI locus demands repeated
      backcrossing to get hold of the specific genomic region underlying an observed
      phenotype. To facilitate mapping of HI loci between C. briggsae and C. sp.9, an
      efficient mapping method and a genetic map ideally consisting of dominant markers
      are required for systematic introgression of genomic fragments between the two
      species. We developed a fast and cost-effective method for high throughput
      mapping of dominant loci with resolution up to 1 million bps in C. briggsae. The
      method takes advantage of the introgression between C. briggsae and C. sp.9
      followed by PCR genotyping using C. briggsae specific primers. Importantly, the
      mapping results can not only serve as an effective way for estimating the
      chromosomal position of a genetic locus in C. briggsae, but also provides size
      information for the introgression fragment in an otherwise C. sp.9 background. In
      addition, it also helps generate introgression line as a side-product that is
      invaluable for the subsequent mapping of HI loci. The method will greatly
      facilitate the construction of a genetic map consisting of dominant markers and
      pave the way for systematic isolation of HI loci between C. briggsae and C. sp.9
      which has so far not been attempted between nematode species. The method is
      designed for mapping of a dominant allele, but can be easily adapted for mapping
      of any other type of alleles in any other species if introgression between a
      sister species pair is feasible.

PMID- 22952756
TI  - Plasma HIV viral rebound following protocol-indicated cessation of ART commenced
      in primary and chronic HIV infection.
AB  - OBJECTIVES: The magnitude of HIV viral rebound following ART cessation has
      consequences for clinical outcome and onward transmission. We compared plasma
      viral load (pVL) rebound after stopping ART initiated in primary (PHI) and
      chronic HIV infection (CHI). DESIGN: Two populations with protocol-indicated ART
      cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials. METHODS:
      Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using
      survival analysis. Differences in pVL between PHI and CHI populations 4 weeks
      after stopping ART were examined using linear and logistic regression.
      Differences in pVL slopes up to 48 weeks were examined using linear mixed models
      and viral burden was estimated through a time-averaged area-under-pVL curve. CHI
      participants were categorised by nadir CD4 at ART stop. RESULTS: Of 171 PHI
      participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95%
      CI 48-51) weeks after stopping ART. Four weeks after stopping treatment, although
      the proportion with pVL >= 400 copies/ml was similar (78% PHI versus 79% CHI),
      levels were 0.45 (95% CI 0.26-0.64) log(10) copies/ml lower for PHI versus CHI,
      and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with
      higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500
      cells/mm(3) was comparable to that experienced by PHI participants. CONCLUSIONS:
      Stopping ART initiated in PHI and CHI was associated with viral rebound to levels
      conferring increased transmission risk, although the level of rebound was
      significantly lower and sustained in PHI compared to CHI.

PMID- 22952762
TI  - Levels of integration in cognitive control and sequence processing in the
      prefrontal cortex.
AB  - Cognitive control is necessary to flexibly act in changing environments. Sequence
      processing is needed in language comprehension to build the syntactic structure
      in sentences. Functional imaging studies suggest that sequence processing engages
      the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control
      processes additionally recruit bilateral rostral lateral PFC regions. The present
      study aimed to investigate these two types of processes in one experimental
      paradigm. Sequence processing was manipulated using two different sequencing
      rules varying in complexity. Cognitive control was varied with different cue-sets
      that determined the choice of a sequencing rule. Univariate analyses revealed
      distinct PFC regions for the two types of processing (i.e. sequence processing:
      left ventrolateral PFC and cognitive control processing: bilateral dorsolateral
      and rostral PFC). Moreover, in a common brain network (including left lateral PFC
      and intraparietal sulcus) no interaction between sequence and cognitive control
      processing was observed. In contrast, a multivariate pattern analysis revealed an
      interaction of sequence and cognitive control processing, such that voxels in
      left lateral PFC and parietal cortex showed different tuning functions for tasks
      involving different sequencing and cognitive control demands. These results
      suggest that the difference between the process of rule selection (i.e. cognitive
      control) and the process of rule-based sequencing (i.e. sequence processing) find
      their neuronal underpinnings in distinct activation patterns in lateral PFC.
      Moreover, the combination of rule selection and rule sequencing can shape the
      response of neurons in lateral PFC and parietal cortex.

PMID- 22952763
TI  - Expression of human paraoxonase 1 decreases superoxide levels and alters
      bacterial colonization in the gut of Drosophila melanogaster.
AB  - Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple
      enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum
      sensing in bacteria and with reactive oxygen species (ROS) in humans and mice.
      PON1 gene mutations have been linked to multiple traits, including aging, and
      diseases of the cardiovascular, nervous and gastrointestinal system. The
      overlapping enzymatic activities in the PON family members and high linkage
      disequilibrium rates within their polymorphisms confound animal and human studies
      of PON1 function. In contrast, arthropods such as Drosophila melanogaster have no
      PON homologs, resulting in an ideal model to study interactions between PON
      genotype and host phenotypes. We hypothesized that expression of PON1 in D.
      melanogaster would alter ROS. We found that PON1 alters expression of multiple
      oxidative stress genes and decreases superoxide anion levels in normal and germ
      free D. melanogaster. We also found differences in the composition of the gut
      microbiota, with a remarkable increase in levels of Lactobacillus plantarum and
      associated changes in expression of antimicrobial and cuticle-related genes. PON1
      expression directly decreased superoxide anion levels and altered bacterial
      colonization of the gut and its gene expression profile, highlighting the complex
      nature of the interaction between host genotype and gut microbiota. We speculate
      that the interaction between some genotypes and human diseases may be mediated by
      the presence of certain gut bacteria that can induce specific immune responses in
      the gut and other host tissues.

PMID- 22952764
TI  - Generation of a novel MMTV-tTA transgenic mouse strain for the targeted
      expression of genes in the embryonic and postnatal mammary gland.
AB  - We have generated a new and improved transgenic mouse strain that permits a
      temporally controlled expression of transgenes throughout mammary gland
      development. High expression of the tetracycline-regulatible transactivator (tTA)
      under control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) is
      restricted to mammary epithelial cells and the salivary gland. The novel MMTV-tTA
      mouse strain induces a sustained transactivation of responder transgenes, which
      can be swiftly suppressed through administration of doxycycline (Dox). An
      important characteristic of this strain is its expression in early progenitor
      cells of mammary gland anlagen beginning at day 13.5 of embryonic development. We
      show here that the MMTV-tTA can be used in combination with GFP reporter strains
      to visualize CK8/CK14-dual positive progenitors in newborn females and their
      derived basal and luminal epithelial cell lineages in adult females. Our
      observations suggest that the novel MMTV-tTA can be utilized to express exogenous
      proteins in multipotent mammary progenitors during the earliest stages of mammary
      gland development to assess their biological significance throughout
      mammogenesis. Moreover, we demonstrate that the expression of the MMTV-tTA is
      sustained during mammary gland tumorigenesis in female mice expressing wildtype
      ErbB2. This makes this strain particular valuable to target the expression of
      exogenous proteins into developing mammary tumors to assess their significance in
      biological processes, such as tumor cell growth and survival, metabolism, and
      metastasis.

PMID- 22952765
TI  - Atomistic mechanism of microRNA translation upregulation via molecular dynamics
      simulations.
AB  - MicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles
      in animals and plants. Recently, miR369-3 was found to upregulate translation of
      TNFalpha mRNA in quiescent (G0) mammalian cell lines. Knock down and
      immunofluorescence experiments suggest that microRNA-protein complexes (with FXR1
      and AGO2) are necessary for the translation upregulation. However the molecular
      mechanism of microRNA translation activation is poorly understood. In this study
      we constructed the microRNA-mRNA-AGO2-FXR1 quadruple complex by bioinformatics
      and molecular modeling, followed with all atom molecular dynamics simulations in
      explicit solvent to investigate the interaction mechanisms for the complex. A
      combined analysis of experimental and computational data suggests that AGO2-FXR1
      complex relocalize microRNA:mRNA duplex to polysomes in G0. The two strands of
      dsRNA are then separated upon binding of AGO2 and FXR1. Finally, polysomes may
      improve the translation efficiency of mRNA. The mutation research confirms the
      stability of microRNA-mRNA-FXR1 and illustrates importance of key residue of
      Ile304. This possible mechanism can shed more light on the microRNA-dependent
      upregulation of translation.

PMID- 22952766
TI  - A splice site mutation in laminin-alpha2 results in a severe muscular dystrophy
      and growth abnormalities in zebrafish.
AB  - Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous
      group of inherited muscle disorders. In patients, muscle weakness is usually
      present at or shortly after birth and is progressive in nature. Merosin deficient
      congenital muscular dystrophy (MDC1A) is a form of CMD caused by a defect in the
      laminin-alpha2 gene (LAMA2). Laminin-alpha2 is an extracellular matrix protein
      that interacts with the dystrophin-dystroglycan (DGC) complex in membranes
      providing stability to muscle fibers. In an N-ethyl-N-nitrosourea mutagenesis
      screen to develop zebrafish models of neuromuscular diseases, we identified a
      mutant fish that exhibits severe muscular dystrophy early in development. Genetic
      mapping identified a splice site mutation in the lama2 gene. This splice site is
      highly conserved in humans and this mutation results in mis-splicing of RNA and a
      loss of protein function. Homozygous lama2 mutant zebrafish, designated
      lama2(cl501/cl501), exhibited reduced motor function and progressive degeneration
      of skeletal muscles and died at 8-15 days post fertilization. The skeletal
      muscles exhibited damaged myosepta and detachment of myofibers in the affected
      fish. Laminin-alpha2 deficiency also resulted in growth defects in the brain and
      eye of the mutant fish. This laminin-alpha2 deficient mutant fish represents a
      novel disease model to develop therapies for modulating splicing defects in
      congenital muscular dystrophies and to restore the muscle function in human
      patients with CMD.

PMID- 22952767
TI  - Hemifield effects in multiple identity tracking.
AB  - In everyday life, we often need to attentively track moving objects. A previous
      study has claimed that this tracking occurs independently in the left and right
      visual hemifields (Alvarez & Cavanagh, 2005, Psychological Science,16, 637-647).
      Specifically, it was shown that observers were much more accurate at tracking
      objects that were spread over both visual hemifields as opposed to when all were
      confined to a single visual hemifield. In that study, observers were not required
      to remember the identities of the objects. Conversely, in real life, there is
      seldom any benefit to tracking an object unless you can also recall its identity.
      It has been predicted that when observers are required to remember the identities
      of the tracked objects a bilateral advantage should no longer be observed (Oksama
      & Hyona, 2008, Cognitive Psychology, 56, 237-283). We tested this prediction and
      found that a bilateral advantage still occurred, though it was not as strong as
      when observers were not required to remember the identities of the targets. Even
      in the later case we found that tracking was not completely independent in the
      two visual hemifields. We present a combined model of multiple object tracking
      and multiple identity tracking that can explain our data.

PMID- 22952768
TI  - Molecular diagnosis of Usher syndrome: application of two different next
      generation sequencing-based procedures.
AB  - Usher syndrome (USH) is a clinically and genetically heterogeneous disorder
      characterized by visual and hearing impairments. Clinically, it is subdivided
      into three subclasses with nine genes identified so far. In the present study, we
      investigated whether the currently available Next Generation Sequencing (NGS)
      technologies are already suitable for molecular diagnostics of USH. We analyzed a
      total of 12 patients, most of which were negative for previously described
      mutations in known USH genes upon primer extension-based microarray genotyping.
      We enriched the NGS template either by whole exome capture or by Long-PCR of the
      known USH genes. The main NGS sequencing platforms were used: SOLiD for whole
      exome sequencing, Illumina (Genome Analyzer II) and Roche 454 (GS FLX) for the
      Long-PCR sequencing. Long-PCR targeting was more efficient with up to 94% of USH
      gene regions displaying an overall coverage higher than 25*, whereas whole exome
      sequencing yielded a similar coverage for only 50% of those regions. Overall this
      integrated analysis led to the identification of 11 novel sequence variations in
      USH genes (2 homozygous and 9 heterozygous) out of 18 detected. However, at least
      two cases were not genetically solved. Our result highlights the current
      limitations in the diagnostic use of NGS for USH patients. The limit for whole
      exome sequencing is linked to the need of a strong coverage and to the correct
      interpretation of sequence variations with a non obvious, pathogenic role,
      whereas the targeted approach suffers from the high genetic heterogeneity of USH
      that may be also caused by the presence of additional causative genes yet to be
      identified.

PMID- 22952769
TI  - Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin
      sulfate but not critical for skeletal development.
AB  - Chondroitin sulfate (CS) is a linear polysaccharide consisting of repeating
      disaccharide units of N-acetyl-D-galactosamine and D-glucuronic acid residues,
      modified with sulfated residues at various positions. Based on its structural
      diversity in chain length and sulfation patterns, CS provides specific biological
      functions in cell adhesion, morphogenesis, neural network formation, and cell
      division. To date, six glycosyltransferases are known to be involved in the
      biosynthesis of chondroitin saccharide chains, and a hetero-oligomer complex of
      chondroitin sulfate synthase-1 (CSS1)/chondroitin synthase-1 and chondroitin
      sulfate synthase-2 (CSS2)/chondroitin polymerizing factor is known to have the
      strongest polymerizing activity. Here, we generated and analyzed CSS2(-/-) mice.
      Although they were viable and fertile, exhibiting no overt morphological
      abnormalities or osteoarthritis, their cartilage contained CS chains with a
      shorter length and at a similar number to wild type. Further analysis using CSS2(
      /-) chondrocyte culture systems, together with siRNA of CSS1, revealed the
      presence of two CS chain species in length, suggesting two steps of CS chain
      polymerization; i.e., elongation from the linkage region up to Mr ~10,000, and
      further extension. There, CSS2 mainly participated in the extension, whereas CSS1
      participated in both the extension and the initiation. Our study demonstrates the
      distinct function of CSS1 and CSS2, providing a clue in the elucidation of the
      mechanism of CS biosynthesis.

PMID- 22952770
TI  - How to open the treasure chest? Optimising DNA extraction from herbarium
      specimens.
AB  - Herbarium collections are potentially an enormous resource for DNA studies, but
      the use of herbarium specimens in molecular studies has thus far been slowed down
      by difficulty in obtaining amplifiable DNA. Here we compare a set of commercially
      available DNA extraction protocols and their performance in terms of DNA purity
      and yield, and PCR amplification success as measured by using three
      differentially sized markers, the rbcL barcoding marker (cpDNA), the LEAFY exon 3
      (nrDNA), and the trnL((UAA)) P6 loop (cpDNA). Results reveal large differences
      between extraction methods, where DNA purity rather than yield is shown to be
      strongly correlated with PCR success. Amplicon size shows similarly strong
      correlation with PCR success, with the shortest fragment showing the highest
      success rate (78%, P6 loop, 10-143 base pairs (bp)) and the largest fragment the
      lowest success (10%, rbcL, 670 bp). The effect of specimen preparation method on
      PCR success was also tested. Results show that drying method strongly affects PCR
      success, especially the availability of fragments longer than 250 bp, where
      longer fragments are more available for PCR amplification in air dried material
      compared to alcohol dried specimens. Results from our study indicate that
      projects relying on poor-quality starting material such as herbarium or scat
      samples should focus on extracting pure DNA and aim to amplify short target
      regions (<200-300 bp) in order to maximise outcomes. Development of shorter
      barcoding regions, or mini-barcodes within existing ones should be of high
      importance as only a few options are currently available; this is particularly
      important if we hope to incorporate the millions of herbarium samples available
      into barcoding initiatives and other molecular studies.

PMID- 22952771
TI  - Breast milk from Tanzanian women has divergent effects on cell-free and cell
      associated HIV-1 infection in vitro.
AB  - Transmission of HIV-1 during breastfeeding is a significant source of new
      pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers
      contains both cell-free and cell-associated virus; however, the impact of breast
      milk on HIV-1 infectivity remains poorly understood. In the present study, breast
      milk was collected from HIV-positive and HIV-negative Tanzanian women attending
      antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro
      against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free
      R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of
      HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively correlated
      with milk levels of sialyl-Lewis(X) from HIV-positive donors. In contrast, milk
      from 8 of 16 subjects enhanced infection with cell-associated HIV-1 regardless of
      donor serostatus. Milk from two of these subjects contained high levels of
      multiple pro-inflammatory cytokines including TNFalpha, IL-1beta, IL-6, IL-8, MIP
      1alpha, MIP-1beta, MCP-1 and IP-10, and enhanced cell-associated HIV-1 infection
      at dilutions as high as 1?500. These findings indicate that breast milk contains
      innate factors with divergent activity against cell-free and cell-associated HIV
      1 in vitro. Enhancement of cell-associated HIV-1 infection by breast milk may be
      associated with inflammatory conditions in the mother and may contribute to
      infant infection during breastfeeding.

PMID- 22952772
TI  - Altered expression of porcine Piwi genes and piRNA during development.
AB  - Three Sus scrofa Piwi genes (Piwil1, Piwil2 and Piwil4) encoding proteins of 861,
      985 and 853 aminoacids, respectively, were cloned and sequenced. Alignment of the
      Piwi proteins showed the high identity between Sus scrofa and Homo sapiens.
      Relative transcript abundance of porcine Piwil1, Piwil2 and Piwil4 genes in
      testes, ovaries and oocytes derived from sexually immature and mature animals was
      examined using Real-Time PCR. Expression of the three Piwi mRNAs was proved to be
      tissue specific and restricted exclusively to the gonads. In testes of adult pigs
      the highest relative transcript abundance was observed for the Sus scrofa Piwil1
      gene. On the other hand, in testes of neonatal pigs the Piwil1 transcript level
      was over 2-fold reduced while the level of Piwil2 transcript was higher. As
      regards the expression of the Piwil4 transcript, its level was 34-fold elevated
      in testes of neonatal piglet when compared to adult male. In ovaries of
      prepubertal and pubertal female pigs transcript abundance of the three Piwi genes
      was significantly reduced in comparison with testes. However, similarly to
      testes, in ovaries of neonatal pigs the Piwil2 gene was characterized by the
      highest relative transcript abundance among the three Piwi genes analysed. In
      prepubertal and pubertal oocytes Piwil1 transcript was the most abundant whereas
      the expression of Piwil4 was undetectable. We also demonstrated that expression
      of piRNA occurs preferentially in the gonads of adult male and female pigs.
      Moreover, a piRNA subset isolated from ovaries was 2-3 nucleotides longer than
      the piRNA from testes.

PMID- 22952773
TI  - Decline in HIV prevalence among young men in the general population of Cotonou,
      Benin, 1998-2008.
AB  - OBJECTIVE: To assess changes in the prevalence of HIV and other sexually
      transmitted infections, as well as in different proximal and distal factors
      related to HIV infection, in the general population of Cotonou between 1998 and
      2008, while an intensive preventive intervention targeting the sex work milieu
      was ongoing. METHODS: A two-stage cluster sampling procedure was used to select
      the participants in each study. Subjects aged 15-49 who agreed to participate
      were interviewed and tested for HIV, syphilis, HSV-2, gonorrhoea and chlamydia.
      We used the Roa-Scott Chi-square test (proportions) and the Student's t test
      (means) for bivariate comparisons, and adjusted logistic regression models taking
      into account the cluster effect for multivariate analyses. RESULTS: HIV
      prevalence decreased significantly in men (3.4% in 1998 versus 2.0% in 2008, p =
      0.048), especially in those aged 15-29 (3.0% to 0.5%, p = 0.002). Among men, the
      prevalence of gonorrhoea decreased significantly (1.1% to 0.3%, p = 0.046) while
      HSV-2 prevalence increased from 12.0% to 18.1% (p = 0.0003). The proportion of
      men who reported condom use at least once (29.3% to 61.0%, p<0.0001) and of those
      having attained a secondary educational level or more (17.1% to 61.3%, p<0.0001)
      also increased significantly. There was an overall decrease in the prevalence of
      syphilis (1.5% to 0.6%, p = 0.0003). CONCLUSION: This is the first population
      based study reporting a significant decline in HIV prevalence among young men in
      an African setting where overall prevalence has never reached 5%. The decline
      occurred while preventive interventions targeting the sex work milieu were
      ongoing and the educational level was increasing.

PMID- 22952774
TI  - Role of donor-specific regulatory T cells in long-term acceptance of rat hind
      limb allograft.
AB  - BACKGROUND: Vascularized bone marrow transplantation (VBMT) is widely accepted as
      an efficient means of establishing chimerism and inducing tolerance. However, the
      mechanism underlying is poorly understood. Recently, regulatory T cells (Tregs)
      have been shown to play an important role in regulating immune responses to
      allogeneic antigens. In this study, we explored the role of Tregs in the
      induction of tolerance in an allogeneic hind limb transplantation model.
      METHODOLOGY/PRINCIPAL FINDINGS: Forty-eight Lewis rats were divided into 6
      groups. They received isografts and allografts from Brown-Norway hind limbs.
      Recipients in groups 1 and 2 received isografts and those in the other groups
      received allografts. The bone components of donor limbs were kept intact in
      groups 1, 3, and 5 but removed before transplantation into groups 2, 4, and 6.
      Tapered cyclosporin A (CsA) was administered to recipients in groups 5 and 6
      after transplantation. During the 100-day observation period, all isografts
      survived, but the allografts in groups 3 and 4 were rejected within 8 to 12 days.
      CsA-treated intact allografts survived rejection-free for more than 100 days, and
      CsA-treated allografts lacking bone elements were rejected within 2 months.
      Stable peripheral chimerism and myeloid chimerism were observed in group 5.
      Declining peripheral chimerism and a lack of myeloid chimerism were observed in
      group 6. Donor-specific Tregs were exclusively detected in both peripheral blood
      and in the spleens of long-term recipient rats in group 5, with an increased
      FoxP3 mRNA expression in the allografts. This was further demonstrated to be
      responsible for donor-specific hyporeactivity by in vitro one-way mixed
      lymphocyte reaction (MLR). CONCLUSION/SIGNIFICANCE: Bone components in the
      allogeneic hind limbs can induce myeloid chimerism and donor-specific Tregs may
      be essential to tolerance induction. The bone-removal hind limb model may be a
      suitable counterpart to the induction of tolerance in the study of limb
      transplantation.

PMID- 22952775
TI  - Pristimerin causes G1 arrest, induces apoptosis, and enhances the
      chemosensitivity to gemcitabine in pancreatic cancer cells.
AB  - Despite rapid advances in chemotherapy and surgical resection strategies,
      pancreatic cancer remains the fourth leading cause of cancer related deaths in
      the United States with a 5-year survival rate of less than 5%. Therefore, novel
      therapeutic agents for the prevention and treatment of pancreatic cancer are
      urgently needed. The aim of this study was to investigate the effect of
      pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae
      and Hippocrateaceae, on inhibition of cell proliferation and induction of
      apoptosis in three pancreatic cancer cells, BxPC-3, PANC-1 and AsPC-1, in both
      monotherapy and in combination with gemcitabine. Treatment with pristimerin
      decreased the cell proliferation of all three pancreatic cancer cells in a dose-
      and time-dependent manner. Treatment of pancreatic cancer cells with pristimerin
      also resulted in G1-phase arrest which was strongly associated with a marked
      decrease in the level of cyclins (D1 and E) and cyclin-dependent kinases (cdk2,
      cdk4 and cdk6 ) with concomitant induction of WAF1/p21 and KIP1/p27. Pristimerin
      treatment also resulted in apoptotic cell death, cleavage of caspase-3,
      modulation in the expressions of Bcl-2 family proteins, inhibition of the
      translocation and DNA-binding activity of NF-kappaB. In addition, pristimerin
      potentiated the growth inhibition and apoptosis inducing effects of gemcitabine
      in all three pancreatic cancer cells, at least in part, by inhibiting
      constitutive as well as gemcitabine-induced activation of NF-kappaB in both its
      DNA-binding activity and transcriptional activity. Taken together, these data
      provide the first evidence that pristimerin has strong potential for development
      as a novel agent against pancreatic cancer.

PMID- 22952776
TI  - Novel PTCH1 mutations in patients with keratocystic odontogenic tumors screened
      for nevoid basal cell carcinoma (NBCC) syndrome.
AB  - Keratocystic odontogenic tumors (KCOTs) are cystic tumors that arise sporadically
      or associated with nevoid basal cell carcinoma syndrome (NBCCS). NBCCS is a rare
      autosomal dominantly inherited disease mainly characterized by multiple basal
      cell carcinomas, KCOTs of the jaws and a variety of other tumors. PTCH1 mutation
      can be found both in sporadic or NBCCS associated KCOTs. The aim of the current
      study was to assess whether a combined clinical and bio-molecular approach could
      be suitable for the detection of NBCCS among patients with a diagnosis of
      keratocystic odontogenic tumors (KCOTs). The authors collected keratocystic
      odontogenic tumors recorded in the database of the Pathology Department of the
      University of Modena and Reggio Emilia during the period 1991-2011. Through
      interviews and examinations, family pedigrees were drawn for all patients
      affected by these odontogenic lesions. We found out that 18 of the 70 patients
      with KCOTs and/or multiple basal cell carcinomas actually met the clinical
      criteria for the diagnosis of NBCCS. A wide inter- and intra-familial phenotypic
      variability was evident in the families. Ameloblastomas (AMLs) were reported in
      two probands that are also carriers of the PCTH1 germline mutations. Nine
      germline mutations in the PTCH1 gene, 5 of them novel, were evident in 14 tested
      probands. The clinical evaluation of the keratocystic odontogenic tumors can be
      used as screening for the detection of families at risk of NBCCS. Keratocystic
      odontogenic lesions are uncommon, and their discovery deserves the search for
      associated cutaneous basal cell carcinomas and other benign and malignant tumors
      related to NBCCS.

PMID- 22952777
TI  - Supplementing with non-glycoside hydrolase proteins enhances enzymatic
      deconstruction of plant biomass.
AB  - The glycoside hydrolases (GH) of Caldicellulosiruptor bescii are thermophilic
      enzymes, and therefore they can hydrolyze plant cell wall polysaccharides at high
      temperatures. Analyses of two C. bescii glycoside hydrolases, CbCelA-TM1 and
      CbXyn10A with cellulase and endoxylanase activity, respectively, demonstrated
      that each enzyme is highly thermostable under static incubation at 70 degrees C.
      Both enzymes, however, rapidly lost their enzymatic activities when incubated at
      70 degrees C with end-over-end shaking. Since crowding conditions, even at low
      protein concentrations, seem to influence enzymatic properties, three non
      glycoside hydrolase proteins were tested for their capacity to stabilize the
      thermophilic proteins at high temperatures. The three proteins investigated were
      a small heat shock protein CbHsp18 from C. bescii, a histone MkHistone1 from
      Methanopyrus kandleri, and bovine RNase A, from a commercial source.
      Fascinatingly, each of these proteins increased the thermostability of the
      glycoside hydrolases at 70 degrees C during end-over-end shaking incubation, and
      this property translated into increases in hydrolysis of several substrates
      including the bioenergy feedstock Miscanthus. Furthermore, MkHistone1 and RNase A
      also altered the initial products released from the cello-oligosaccharide
      cellopentaose during hydrolysis with the cellodextrinase CbCdx1A, which further
      demonstrated the capacity of the three non-GH proteins to influence hydrolysis of
      substrates by the thermophilic glycoside hydrolases. The non-GH proteins used in
      the present report were small proteins derived from each of the three lineages of
      life, and therefore expand the space from which different polypeptides can be
      tested for their influence on plant cell wall hydrolysis, a critical step in the
      emerging biofuel industry.

PMID- 22952778
TI  - Influence of age on brain edema formation, secondary brain damage and
      inflammatory response after brain trauma in mice.
AB  - After traumatic brain injury (TBI) elderly patients suffer from higher mortality
      rate and worse functional outcome compared to young patients. However,
      experimental TBI research is primarily performed in young animals. Aim of the
      present study was to clarify whether age affects functional outcome,
      neuroinflammation and secondary brain damage after brain trauma in mice. Young (2
      months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to
      a controlled cortical impact injury (CCI) on the right parietal cortex. Animals
      of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the
      end of the observation periods, contusion volume, brain water content, neurologic
      function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory
      cytokine expression in brain and lung, blood differential cell count) were
      determined. Old animals showed worse neurological function 72 h after CCI and a
      high mortality rate (19.2%) compared to young (0%). This did not correlate with
      histopathological damage, as contusion volumes were equal in both age groups.
      Although a more pronounced brain edema formation was detected in old mice 24
      hours after TBI, lack of correlation between brain water content and neurological
      deficit indicated that brain edema formation is not solely responsible for age
      dependent differences in neurological outcome. Brains of old naive mice were
      about 8% smaller compared to young naive brains, suggesting age-related brain
      atrophy with possible decline in plasticity. Onset of cerebral inflammation
      started earlier and primarily ipsilateral to damage in old mice, whereas in young
      mice inflammation was delayed and present in both hemispheres with a
      characteristic T cell migration pattern. Pulmonary interleukin 1beta expression
      was up-regulated after cerebral injury only in young, not aged mice. The results
      therefore indicate that old animals are prone to functional deficits and strong
      ipsilateral cerebral inflammation without major differences in morphological
      brain damage compared to young.

PMID- 22952779
TI  - Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but
      increases metastases in TRAMP prostate cancer prone mice.
AB  - Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF
      beta superfamily, is over-expressed by many common cancers including those of the
      prostate (PCa) and its expression is linked to cancer outcome. We have evaluated
      the effect of MIC-1/GDF15 overexpression on PCa development and spread in the
      TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed
      with MIC-1/GDF15 overexpressing mice (MIC-1(fms)) to produce syngeneic
      TRAMP(fmsmic-1) mice. Survival rate, prostate tumor size, histopathological
      grades and extent of distant organ metastases were compared. Metastasis of TC1
      T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression,
      was compared by injecting intravenously into MIC-1(fms) and syngeneic C57BL/6
      mice. Whilst TRAMP(fmsmic-1) survived on average 7.4 weeks longer, had
      significantly smaller genitourinary (GU) tumors and lower PCa histopathological
      grades than TRAMP mice, more of these mice developed distant organ metastases.
      Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC
      1(fms) mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC
      1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but
      may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all
      cancer treatments and metastasis is the major cause of cancer treatment failure
      and cancer deaths, these results, if applicable to humans, may have a direct
      impact on patient care.

PMID- 22952780
TI  - Development and evaluation of a simple and effective prediction approach for
      identifying those at high risk of dyslipidemia in rural adult residents.
AB  - BACKGROUND: Dyslipidemia is an extremely prevalent but preventable risk factor
      for cardiovascular disease. However, many dyslipidemia patients remain undetected
      in resource limited settings. The study was performed to develop and evaluate a
      simple and effective prediction approach without biochemical parameters to
      identify those at high risk of dyslipidemia in rural adult population. METHODS:
      Demographic, dietary and lifestyle, and anthropometric data were collected by a
      cross-sectional survey from 8,914 participants living in rural areas aged 35-78
      years. There were 6,686 participants randomly selected into a training group for
      constructing the artificial neural network (ANN) and logistic regression (LR)
      prediction models. The remaining 2,228 participants were assigned to a validation
      group for performance comparisons of ANN and LR models. The predictors of
      dyslipidemia risk were identified from the training group using multivariate
      logistic regression analysis. Predictive performance was evaluated by receiver
      operating characteristic (ROC) curve. RESULTS: Some risk factors were
      significantly associated with dyslipidemia, including age, gender, educational
      level, smoking, high-fat diet, vegetable and fruit intake, family history,
      physical activity, and central obesity. For the ANN model, the sensitivity,
      specificity, positive and negative likelihood ratio, positive and negative
      predictive values were 90.41%, 76.66%, 3.87, 0.13, 76.33%, and 90.58%,
      respectively, while LR model were only 57.37%, 70.91%, 1.97, 0.60, 62.09%, and
      66.73%, respectively. The area under the ROC cure (AUC) value of the ANN model
      was 0.86+/-0.01, showing more accurate overall performance than traditional LR
      model (AUC = 0.68+/-0.01, P<0.001). CONCLUSION: The ANN model is a simple and
      effective prediction approach to identify those at high risk of dyslipidemia, and
      it can be used to screen undiagnosed dyslipidemia patients in rural adult
      population. Further work is planned to confirm these results by incorporating
      multi-center and longer follow-up data.

PMID- 22952782
TI  - Bats track and exploit changes in insect pest populations.
AB  - The role of bats or any generalist predator in suppressing prey populations
      depends on the predator's ability to track and exploit available prey. Using a
      qPCR fecal DNA assay, we document significant association between numbers of
      Brazilian free-tailed bats (Tadarida brasiliensis) consuming corn earworm (CEW)
      moths (Helicoverpa zea) and seasonal fluctuations in CEW populations. This result
      is consistent with earlier research linking the bats' diet to patterns of
      migration, abundance, and crop infestation by important insect pests. Here we
      confirm opportunistic feeding on one of the world's most destructive insects and
      support model estimates of the bats' ecosystem services. Regression analysis of
      CEW consumption versus the moth's abundance at four insect trapping sites further
      indicates that bats track local abundance of CEW within the regional landscape.
      Estimates of CEW gene copies in the feces of bats are not associated with
      seasonal or local patterns of CEW abundance, and results of captive feeding
      experiments indicate that our qPCR assay does not provide a direct measure of
      numbers or biomass of prey consumed. Our results support growing evidence for the
      role of generalist predators, and bats specifically, as agents for biological
      control and speak to the value of conserving indigenous generalist predators.

PMID- 22952781
TI  - In vivo quantification reveals extensive natural variation in mitochondrial form
      and function in Caenorhabditis briggsae.
AB  - We have analyzed natural variation in mitochondrial form and function among a set
      of Caenorhabditis briggsae isolates known to harbor mitochondrial DNA structural
      variation in the form of a heteroplasmic nad5 gene deletion (nad5Delta) that
      correlates negatively with organismal fitness. We performed in vivo
      quantification of 24 mitochondrial phenotypes including reactive oxygen species
      level, membrane potential, and aspects of organelle morphology, and observed
      significant among-isolate variation in 18 traits. Although several mitochondrial
      phenotypes were non-linearly associated with nad5Delta levels, most of the among
      isolate phenotypic variation could be accounted for by phylogeographic clade
      membership. In particular, isolate-specific mitochondrial membrane potential was
      an excellent predictor of clade membership. We interpret this result in light of
      recent evidence for local adaptation to temperature in C. briggsae. Analysis of
      mitochondrial-nuclear hybrid strains provided support for both mtDNA and nuclear
      genetic variation as drivers of natural mitochondrial phenotype variation. This
      study demonstrates that multicellular eukaryotic species are capable of extensive
      natural variation in organellar phenotypes and highlights the potential of
      integrating evolutionary and cell biology perspectives.

PMID- 22952783
TI  - Access to cancer screening in people with learning disabilities in the UK: cohort
      study in the health improvement network, a primary care research database.
AB  - OBJECTIVES: To assess whether people with learning disability in the UK have
      poorer access to cancer screening. DESIGN: Four cohort studies comparing people
      with and without learning disability, within the recommended age ranges for
      cancer screening in the UK. We used Poisson regression to determine relative
      incidence rates of cancer screening. SETTING: The Health Improvement Network, a
      UK primary care database with over 450 General practices. PARTICIPANTS:
      Individuals with a recorded diagnosis of learning disability including general
      diagnostic terms, specific syndromes, chromosomal abnormalities and autism in
      their General Practitioner computerised notes. For each type of cancer screening,
      a comparison cohort of up to six people without learning disability was selected
      for each person with a learning disability, using stratified sampling on age
      within GP practice. MAIN OUTCOME MEASURES: Incidence rate ratios for receiving 1)
      a cervical smear test, 2) a mammogram, 3) a faecal occult blood test and 4) a
      prostate specific antigen test. RESULTS: Relative rates of screening for all four
      cancers were significantly lower for people with learning disability. The
      adjusted incidence rate ratios (95% confidence intervals) were Cervical smears:
      Number eligible with learning disability = 6,254; IRR = 0.54 (0.52-0.56).
      Mammograms: Number eligible with learning disability = 2,956; IRR = 0.76 (0.72
      0.81); Prostate Specific Antigen: Number eligible = 3,520; IRR = 0.87 (0.80-0.96)
      and Faecal Occult Blood Number eligible = 6,566; 0.86 (0.78-0.94). Differences in
      screening rates were less pronounced in more socially deprived areas. Disparities
      in cervical screening rates narrowed over time, but were 45% lower in 2008/9,
      those for breast cancer screening appeared to widen and were 35% lower in 2009.
      CONCLUSION: Despite recent incentives, people with learning disability in the UK
      are significantly less likely to receive screening tests for cancer that those
      without learning disability. Other methods for reducing inequalities in access to
      cancer screening should be considered.

PMID- 22952785
TI  - Diel variability in seawater pH relates to calcification and benthic community
      structure on coral reefs.
AB  - Community structure and assembly are determined in part by environmental
      heterogeneity. While reef-building corals respond negatively to warming (i.e.
      bleaching events) and ocean acidification (OA), the extent of present-day natural
      variability in pH on shallow reefs and ecological consequences for benthic
      assemblages is unknown. We documented high resolution temporal patterns in
      temperature and pH from three reefs in the central Pacific and examined how these
      data relate to community development and net accretion rates of early
      successional benthic organisms. These reefs experienced substantial diel
      fluctuations in temperature (0.78 degrees C) and pH (>0.2) similar to the
      magnitude of 'warming' and 'acidification' expected over the next century. Where
      daily pH within the benthic boundary layer failed to exceed pelagic
      climatological seasonal lows, net accretion was slower and fleshy, non-calcifying
      benthic organisms dominated space. Thus, key aspects of coral reef ecosystem
      structure and function are presently related to natural diurnal variability in
      pH.

PMID- 22952784
TI  - A comparison of EGFR mutation testing methods in lung carcinoma: direct
      sequencing, real-time PCR and immunohistochemistry.
AB  - The objective of this study is to compare two EGFR testing methodologies (a
      commercial real-time PCR kit and a specific EGFR mutant immunohistochemistry),
      with direct sequencing and to investigate the limit of detection (LOD) of both
      PCR-based methods. We identified EGFR mutations in 21 (16%) of the 136 tumours
      analyzed by direct sequencing. Interestingly, the Therascreen EGFR Mutation Test
      kit was able to characterize as wild-type one tumour that could not be analyzed
      by direct sequencing of the PCR product. We then compared the LOD of the kit and
      that of direct sequencing using the available mutant tumours. The kit was able to
      detect the presence of a mutation in a 1% dilution of the total DNA in nine of
      the 18 tumours (50%), which tested positive with the real-time quantitative PCR
      method. In all cases, EGFR mutation was identified at a dilution of 5%. Where the
      mutant DNA represented 30% of the total DNA, sequencing was able to detect
      mutations in 12 out of 19 cases (63%). Additional experiments with genetically
      defined standards (EGFR DeltaE746-A750/+ and EGFR L858R/+) yielded similar
      results. Immunohistochemistry (IHC) staining with exon 19-specific antibody was
      seen in eight out of nine cases with E746-A750del detected by direct sequencing.
      Neither of the two tumours with complex deletions were positive. Of the five
      L858R-mutated tumours detected by the PCR methods, only two were positive for the
      exon 21-specific antibody. The specificity was 100% for both antibodies. The LOD
      of the real-time PCR method was lower than that of direct sequencing. The
      mutation specific IHC produced excellent specificity.

PMID- 22952786
TI  - Potent neutralization of botulinum neurotoxin/B by synergistic action of
      antibodies recognizing protein and ganglioside receptor binding domain.
AB  - BACKGROUND: Botulinum neurotoxins (BoNTs), the causative agents for life
      threatening human disease botulism, have been recognized as biological warfare
      agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT
      therapeutics, but the potencies of mAbs against BoNTs are usually less than that
      of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key
      epitopes with development of effective mAb is urgently needed. METHODS AND
      FINDINGS: We selected 3 neutralizing mAbs which recognize different non
      overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against
      BoNT/B. By comparing the neutralizing effects among different combination groups,
      we found that 8E10, response to ganglioside receptor binding site, could synergy
      with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding
      sites. However, the combination of 5G10 with 2F4 blocking protein receptor
      binding sites did not achieve synergistical effects. Moreover, we found that the
      binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might
      cross-protect the challenge of different serotypes of BoNTs in vivo. CONCLUSIONS:
      The combination of two mAbs recognizing different receptors' binding domain in
      BoNTs has a synergistic effect. 8E10 is a potential universal partner for the
      synergistical combination with other mAb against protein receptor binding domain
      in BoNTs of other serotypes.

PMID- 22952787
TI  - HPLC-MS/MS analysis of a traditional Chinese medical formulation of Bu-Yang-Huan
      Wu-Tang and its pharmacokinetics after oral administration to rats.
AB  - Bu-yang-huan-wu-tang (BYHWT) is one of the most popular formulated traditional
      Chinese medicine prescriptions, and is widely for prevention of ischemic cardio
      cerebral vascular diseases and stroke-induced disability. A specific high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been
      developed and validated for simultaneous quantification of the nine main
      bioactive components, i.e., astragaloside I, astragaloside II, astragaloside IV,
      formononetin, ononin, calycosin, calycosin-7-O-beta-d-glucoside, ligustilide and
      paeoniflorin in rat plasma after oral administration of BYHWT extract. This
      method was applied to investigate the pharmacokinetics in conscious and freely
      moving rats. No significant matrix effects were observed. The overall analytical
      procedure was rapid and reproducible, which makes it suitable for quantitative
      analysis of a large number of samples. Among them, three astragalosides and four
      isoflavones in A. membranaceus, ligustilide in Radix Angelicae Sinensis and
      Rhizoma Ligustici Chuanxiong and paeoniflorin in Radix Paeoniae Rubra were
      identified. This developed method was then successfully applied to
      pharmacokinetic studies of the nine bioactive constituents after oral
      administration of BYHWT extracts in rats. The pharmacokinetic data demonstrated
      that astragaloside I, astragaloside II, astragaloside IV and ligustilide
      presented the phenomenon of double peaks. The other herbal ingredients of
      formononetin, ononin, calycosin, calycosin-7-O-beta-d-glucoside and paeoniflorin
      appeared together in a single and plateau absorption phase. These phenomenona
      suggest that these components may have multiple absorption sites, regulation of
      enterohepatic circulation or the gastric emptying rate, or there is ingredient
      ingredient interaction. These pharmacokinetic results provide a constructive
      contribution to better understand the absorption mechanism of BYHWT and to
      support additional clinical evaluation.

PMID- 22952788
TI  - Development of a foot-and-mouth disease virus serotype A empty capsid subunit
      vaccine using silkworm (Bombyx mori) pupae.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals that inflicts severe economic losses in the livestock industry. In 2009,
      FMDV serotype A caused outbreaks of FMD in cattle in China. Although an
      inactivated virus vaccine has proven effective to control FMD, its use may lead
      to new disease outbreaks due to a possible incomplete inactivation of the virus
      during the manufacturing process. Here, we expressed the P1-2A and the 3C coding
      regions of a serotype A FMDV field isolate in silkworm pupae (Bombyx mori) and
      evaluated the immunogenicity of the expression products. Four of five cattle
      vaccinated with these proteins developed high titers of FMDV-specific antibody
      and were completely protected against virulent homologous virus challenge with
      10,000 50% bovine infectious doses (BID(50)). Furthermore, the 50% bovine
      protective dose (PD(50)) test was performed to assess the bovine potency of the
      empty capsid subunit vaccine and was shown to achieve 4.33 PD(50) per dose. These
      data provide evidence that silkworm pupae can be used to express immunogenic FMDV
      proteins. This strategy might be used to develop a new generation of empty capsid
      subunit vaccines against a variety of diseases.

PMID- 22952789
TI  - Use of artificial intelligence to shorten the behavioral diagnosis of autism.
AB  - The Autism Diagnostic Interview-Revised (ADI-R) is one of the most commonly used
      instruments for assisting in the behavioral diagnosis of autism. The exam
      consists of 93 questions that must be answered by a care provider within a
      focused session that often spans 2.5 hours. We used machine learning techniques
      to study the complete sets of answers to the ADI-R available at the Autism
      Genetic Research Exchange (AGRE) for 891 individuals diagnosed with autism and 75
      individuals who did not meet the criteria for an autism diagnosis. Our analysis
      showed that 7 of the 93 items contained in the ADI-R were sufficient to classify
      autism with 99.9% statistical accuracy. We further tested the accuracy of this 7
      question classifier against complete sets of answers from two independent
      sources, a collection of 1654 individuals with autism from the Simons Foundation
      and a collection of 322 individuals with autism from the Boston Autism
      Consortium. In both cases, our classifier performed with nearly 100% statistical
      accuracy, properly categorizing all but one of the individuals from these two
      resources who previously had been diagnosed with autism through the standard ADI
      R. Our ability to measure specificity was limited by the small numbers of non
      spectrum cases in the research data used, however, both real and simulated data
      demonstrated a range in specificity from 99% to 93.8%. With incidence rates
      rising, the capacity to diagnose autism quickly and effectively requires careful
      design of behavioral assessment methods. Ours is an initial attempt to
      retrospectively analyze large data repositories to derive an accurate, but
      significantly abbreviated approach that may be used for rapid detection and
      clinical prioritization of individuals likely to have an autism spectrum
      disorder. Such a tool could assist in streamlining the clinical diagnostic
      process overall, leading to faster screening and earlier treatment of individuals
      with autism.

PMID- 22952790
TI  - KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T
      cells.
AB  - The migration of T lymphocytes is an essential part of the adaptive immune
      response as T cells circulate around the body to carry out immune surveillance.
      During the migration process T cells polarize, forming a leading edge at the cell
      front and a uropod at the cell rear. Our interest was in studying the involvement
      of ion channels in the migration of activated human T lymphocytes as they
      modulate intracellular Ca(2+) levels. Ca(2+) is a key regulator of cellular
      motility. To this purpose, we created protein surfaces made of the bio-polymer
      PNMP and coated with ICAM-1, ligand of LFA-1. The LFA-1 and ICAM-1 interaction
      facilitates T cell movement from blood into tissues and it is critical in immune
      surveillance and inflammation. Activated human T lymphocytes polarized and
      migrated on ICAM-1 surfaces by random walk with a mean velocity of ~6 um/min.
      Confocal microscopy indicated that Kv1.3, CRAC, and TRPM4 channels positioned in
      the leading-edge, whereas KCa3.1 and TRPM7 channels accumulated in the uropod.
      The localization of KCa3.1 and TRPM7 at the uropod was associated with
      oscillations in intracellular Ca(2+) levels that we measured in this cell
      compartment. Further studies with blockers against Kv1.3 (ShK), KCa3.1 (TRAM-34),
      CRAC (SKF-96365), TRPM7 (2-APB), and TRPM4 (glibenclamide) indicated that
      blockade of KCa3.1 and TRPM7, and not Kv1.3, CRAC or TRPM4, inhibits the T cell
      migration. The involvement of TRPM7 in cell migration was confirmed with siRNAs
      against TRPM7. Downregulation of TRPM7 significantly reduced the number of
      migrating T cells and the mean velocity of the migrating T cells. These results
      indicate that KCa3.1 and TRPM7 selectively localize at the uropod of migrating T
      lymphocytes and are key components of the T cell migration machinery.

PMID- 22952791
TI  - Modeling formamide denaturation of probe-target hybrids for improved microarray
      probe design in microbial diagnostics.
AB  - Application of high-density microarrays to the diagnostic analysis of microbial
      communities is challenged by the optimization of oligonucleotide probe
      sensitivity and specificity, as it is generally unfeasible to experimentally test
      thousands of probes. This study investigated the adjustment of hybridization
      stringency using formamide with the idea that sensitivity and specificity can be
      optimized during probe design if the hybridization efficiency of oligonucleotides
      with target and non-target molecules can be predicted as a function of formamide
      concentration. Sigmoidal denaturation profiles were obtained using fluorescently
      labeled and fragmented 16S rRNA gene amplicon of Escherichia coli as the target
      with increasing concentrations of formamide in the hybridization buffer. A linear
      free energy model (LFEM) was developed and microarray-specific nearest neighbor
      rules were derived. The model simulated formamide melting with a denaturant m
      value that increased hybridization free energy (DeltaG degrees ) by 0.173
      kcal/mol per percent of formamide added (v/v). Using the LFEM and specific probe
      sets, free energy rules were systematically established to predict the stability
      of single and double mismatches, including bulged and tandem mismatches. The
      absolute error in predicting the position of experimental denaturation profiles
      was less than 5% formamide for more than 90 percent of probes, enabling a
      practical level of accuracy in probe design. The potential of the modeling
      approach for probe design and optimization is demonstrated using a dataset
      including the 16S rRNA gene of Rhodobacter sphaeroides as an additional target
      molecule. The LFEM and thermodynamic databases were incorporated into a
      computational tool (ProbeMelt) that is freely available at
      http://DECIPHER.cee.wisc.edu.

PMID- 22952792
TI  - Reverse taxonomy for elucidating diversity of insect-associated nematodes: a case
      study with termites.
AB  - BACKGROUND: The molecular operational taxonomic unit (MOTU) has recently been
      applied to microbial and microscopic animal biodiversity surveys. However, in
      many cases, some of the MOTUs cannot be definitively tied to any of the taxonomic
      groups in current databases. To surmount these limitations, the concept of
      "reverse taxonomy" has been proposed, i.e. to primarily list the MOTUs with
      morphological information, and then identify and/or describe them at
      genus/species level using subsamples or by re-isolating the target organisms.
      Nevertheless, the application of "reverse taxonomy" has not been sufficiently
      evaluated. Therefore, the practical applicability of "reverse taxonomy" is tested
      using termite-associated nematodes as a model system for phoretic/parasitic
      organisms which have high habitat specificity and a potential handle (their
      termite host species) for re-isolation attempts. METHODOLOGY: Forty-eight species
      (from 298 colonies) of termites collected from the American tropics and
      subtropics were examined for their nematode associates using the reverse taxonomy
      method and culturing attempts (morphological identification and further
      sequencing efforts). The survey yielded 51 sequence types ( =  MOTUs) belonging
      to 19 tentatively identified genera. Within these, four were identified based on
      molecular data with preliminary morphological observation, and an additional
      seven were identified or characterized from successful culturing, leaving eight
      genera unidentified. CONCLUSIONS: That 1/3 of the genera were not successfully
      identified suggests deficiencies in the depth of available sequences in the
      database and biological characters, i.e. usually isolated as phoretic/parasitic
      stages which are not available for morphological identification, and too many
      undiscovered lineages of nematodes. Although there still is the issue of
      culturability of nematodes, culturing attempts could help to make reverse
      taxonomy methods more effective. However, expansion of the database, i.e.,
      production of more DNA barcodes tied to biological information by finding and
      characterizing additional new and known lineages, is necessary for analyzing
      functional diversity.

PMID- 22952793
TI  - Nectar theft and floral ant-repellence: a link between nectar volume and ant
      repellent traits?
AB  - As flower visitors, ants rarely benefit a plant. They are poor pollinators, and
      can also disrupt pollination by deterring other flower visitors, or by stealing
      nectar. Some plant species therefore possess floral ant-repelling traits. But why
      do particular species have such traits when others do not? In a dry forest in
      Costa Rica, of 49 plant species around a third were ant-repellent at very close
      proximity to a common generalist ant species, usually via repellent pollen.
      Repellence was positively correlated with the presence of large nectar volumes.
      Repellent traits affected ant species differently, some influencing the behaviour
      of just a few species and others producing more generalised ant-repellence. Our
      results suggest that ant-repellent floral traits may often not be pleiotropic,
      but instead could have been selected for as a defence against ant thieves in
      plant species that invest in large volumes of nectar. This conclusion highlights
      to the importance of research into the cost of nectar production in future
      studies into ant-flower interactions.

PMID- 22952794
TI  - Effectiveness of standardized Nursing Care Plans in health outcomes in patients
      with type 2 Diabetes Mellitus: a two-year prospective follow-up study.
AB  - BACKGROUND: Implementation of a standardized language in Nursing Care Plans
      (SNCP) allows for increased efficiency in nursing data management. However, the
      potential relationship with patients health outcomes remains uncertain. The aim
      of this study was to evaluate the effectiveness of SNCP implementation, based on
      North American Nursing Diagnosis Association (NANDA) and Nursing Interventions
      Classification (NIC), in the improvement of metabolic, weight, and blood pressure
      control of Type 2 Diabetes Mellitus (T2DM) patients. METHODS: A two-year
      prospective follow-up study, in routine clinical practice conditions. 31 primary
      health care centers (Spain) participated with 24,124 T2DM outpatients. Data was
      collected from Computerized Clinical Records; SNCP were identified using NANDA
      and NIC taxonomies. Descriptive and ANCOVA analyses were conducted. RESULTS:
      18,320 patients were identified in the Usual Nursing Care (UNC) group and 5,168
      in the SNCP group. At the two-year follow-up, the SNCP group improved all
      parameters except LDL cholesterol and diastolic blood pressure. We analyzed data
      adjustming by the baseline value for these variables and variables with
      statistically significant differences between groups at baseline visit. Results
      indicated a lowering of all parameters except HbA1c, but a statistically
      significant reduction was only observed with diastolic blood pressure results.
      However, the adjusted reduction of diastolic blood pressure is of little clinical
      relevance. Greater differences of control values for diastolic blood pressure,
      HbA1c, LDL-cholesterol and Body Mass Index were found in the SNCP group, but only
      reached statistical significance for HbA1c. A greater proportion of patients with
      baseline HbA1c >=7 decreased to <7% at the two-year follow-up in the SNCP group
      than in the UNC group (16.9% vs. 15%; respectively; p = 0.01). CONCLUSIONS:
      Utilization of SNCP was helpful in achieving glycemic control targets in poorly
      controlled patients with T2DM (HbA1c >=7%). Diastolic blood pressure results were
      slightly improved in the SNCP group compared to the UNC group. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01482481.

PMID- 22952795
TI  - Initial binding of ions to the interhelical loops of divalent ion transporter
      CorA: replica exchange molecular dynamics simulation study.
AB  - Crystal structures of Thermotoga maritima magnesium transporter CorA, reported in
      2006, revealed its homo-pentameric constructions. However, the structure of the
      highly conserved extracellular interhelical loops remains unsolved, due to its
      high flexibility. We have explored the configurations of the loops through
      extensive replica exchange molecular dynamics simulations in explicit solvent
      model with the presence of either Co(III) Hexamine ions or Mg(2+) ions. We found
      that there are multiple binding sites available on the interhelical loops in
      which the negatively charged residues, E316 and E320, are located notably close
      to the positively charged ions during the simulations. Our simulations resolved
      the distinct binding patterns of the two kinds of ions: Co(III) Hexamine ions
      were found to bind stronger with the loop than Mg(2+) ions with binding free
      energy -7.3 kJ/mol lower, which is nicely consistent with the previous data. Our
      study provides an atomic basis description of the initial binding process of
      Mg(2+) ions on the extracellular interhelical loops of CorA and the detailed
      inhibition mechanism of Co(III) Hexamine ions on CorA ions transportation.

PMID- 22952797
TI  - Turning up the heat: increasing temperature and coral bleaching at the high
      latitude coral reefs of the Houtman Abrolhos Islands.
AB  - BACKGROUND: Coral reefs face increasing pressures particularly when on the edge
      of their distributions. The Houtman Abrolhos Islands (Abrolhos) are the
      southernmost coral reef system in the Indian Ocean, and one of the highest
      latitude reefs in the world. These reefs have a unique mix of tropical and
      temperate marine fauna and flora and support 184 species of coral, dominated by
      Acropora species. A significant La Nina event during 2011 produced anomalous
      conditions of increased temperature along the whole Western Australian coastline,
      producing the first-recorded widespread bleaching of corals at the Abrolhos.
      METHODOLOGY/ PRINCIPAL FINDINGS: We examined long term trends in the marine
      climate at the Abrolhos using historical sea surface temperature data (HadISST
      data set) from 1900-2011. In addition in situ water temperature data for the
      Abrolhos (from data loggers installed in 2008, across four island groups) were
      used to determine temperature exposure profiles. Coupled with the results of
      coral cover surveys conducted annually since 2007; we calculated bleaching
      thresholds for monitoring sites across the four Abrolhos groups. CONCLUSIONS/
      SIGNIFICANCE: In situ temperature data revealed maximum daily water temperatures
      reached 29.54 degrees C in March 2011 which is 4.2 degrees C above mean maximum
      daily temperatures (2008-2010). The level of bleaching varied across sites with
      an average of ~12% of corals bleached. Mortality was high, with a mean ~50%
      following the 2011 bleaching event. Prior to 2011, summer temperatures reached a
      mean (across all monitoring sites) of 25.1 degrees C for 2.5 days. However, in
      2011 temperatures reached a mean of 28.1 degrees C for 3.3 days. Longer term
      trends (1900-2011) showed mean annual sea surface temperatures increase by 0.01
      degrees C per annum. Long-term temperature data along with short-term peaks in
      2011, outline the potential for corals to be exposed to more frequent bleaching
      risk with consequences for this high latitude coral reef system at the edge of
      its distribution.

PMID- 22952796
TI  - Biochemical and mass spectrometric characterization of human N-acylethanolamine
      hydrolyzing acid amidase inhibition.
AB  - The mechanism of inactivation of human enzyme N-acylethanolamine-hydrolyzing acid
      amidase (hNAAA), with selected inhibitors identified in a novel fluorescent based
      assay developed for characterization of both reversible and irreversible
      inhibitors, was investigated kinetically and using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 1
      Isothiocyanatopentadecane (AM9023) was found to be a potent, selective and
      reversible hNAAA inhibitor, while two others, 5-((biphenyl-4-yl)methyl)-N,N
      dimethyl-2H-tetrazole-2-carboxamide (AM6701) and N-Benzyloxycarbonyl-L-serine
      beta-lactone (N-Cbz-serine beta-lactone), inhibited hNAAA in a covalent and
      irreversible manner. MS analysis of the hNAAA/covalent inhibitor complexes
      identified modification only of the N-terminal cysteine (Cys126) of the beta
      subunit, confirming a suggested mechanism of hNAAA inactivation by the beta
      lactone containing inhibitors. These experiments provide direct evidence of the
      key role of Cys126 in hNAAA inactivation by different classes of covalent
      inhibitors, confirming the essential role of cysteine for catalysis and
      inhibition in this cysteine N-terminal nucleophile hydrolase enzyme. They also
      provide a methodology for the rapid screening and characterization of large
      libraries of compounds as potential inhibitors of NAAA, and subsequent
      characterization or their mechanism through MALDI-TOF MS based bottom up
      proteomics.

PMID- 22952798
TI  - Effects of chronic exposure to arsenic and estrogen on epigenetic regulatory
      genes expression and epigenetic code in human prostate epithelial cells.
AB  - Chronic exposures to arsenic and estrogen are known risk factors for prostate
      cancer. Though the evidence suggests that exposure to arsenic or estrogens can
      disrupt normal DNA methylation patterns and histone modifications, the mechanisms
      by which these chemicals induce epigenetic changes are not fully understood.
      Moreover, the epigenetic effects of co-exposure to these two chemicals are not
      known. Therefore, the objective of this study was to evaluate the effects of
      chronic exposure to arsenic and estrogen, both alone and in combination, on the
      expression of epigenetic regulatory genes, their consequences on DNA methylation,
      and histone modifications. Human prostate epithelial cells, RWPE-1, chronically
      exposed to arsenic and estrogen alone and in combination were used for analysis
      of epigenetic regulatory genes expression, global DNA methylation changes, and
      histone modifications at protein level. The result of this study revealed that
      exposure to arsenic, estrogen, and their combination alters the expression of
      epigenetic regulatory genes and changes global DNA methylation and histone
      modification patterns in RWPE-1 cells. These changes were significantly greater
      in arsenic and estrogen combination treated group than individually treated
      group. The findings of this study will help explain the epigenetic mechanism of
      arsenic- and/or estrogen-induced prostate carcinogenesis.

PMID- 22952799
TI  - The pox in the North American backyard: Volepox virus pathogenesis in California
      mice (Peromyscus californicus).
AB  - Volepox virus (VPXV) was first isolated in 1985 from a hind foot scab of an
      otherwise healthy California vole (Microtus californicus). Subsequent surveys in
      San Mateo County, CA, revealed serological evidence suggesting that VPXV is
      endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus
      truei) was collected in 1988. Since then, few studies have been conducted
      regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence
      and role as a potential zoonotic agent remain unknown. To increase our
      understanding of VPXV disease progression, we challenged 24 California mice
      (Peromyscus californicus) intranasally with 1.6 * 10(3) PFU of purified VPXV. By
      day five post infection (pi) we observed decreased activity level,
      conjunctivitis, ruffled hair, skin lesions, facial edema, and crusty noses. A
      mortality rate of 54% was noted by day eight pi. In addition, internal organ
      necrosis and hemorrhages were observed during necropsy of deceased or euthanized
      animals. Viral loads in tissues (brain, gonad, kidney, liver, lung, spleen,
      submandibular lymph node, and adrenal gland), bodily secretions (saliva, and
      tears), and excretions (urine, and/or feces) were evaluated and compared using
      real time-PCR and tissue culture. Viral loads measured as high as 2 * 10(9)
      PFU/mL in some organs. Our results suggest that VPXV can cause extreme morbidity
      and mortality within rodent populations sympatric with the known VPXV reservoirs.

PMID- 22952800
TI  - Suppression of extensive neurofilament phosphorylation rescues alpha
      Internexin/peripherin-overexpressing PC12 cells from neuronal cell death.
AB  - Intermediate filament (IF) overproduction induces abnormal accumulation of
      neuronal IF, which is a pathological indicator of some neurodegenerative
      disorders. In our study, alpha-Internexin- and peripherin-overexpressing PC12
      cells (pINT-EGFP and pEGFP-peripherin) were used as models to study
      neuropathological pathways responsible for neurodegenerative diseases. Microarray
      data revealed that Cdk5-related genes were downregulated and Cdk5 regulatory
      subunit-associated protein 3 (GSK-3alpha and GSK-3beta) were upregulated in pINT
      EGFP cells. Increased expression of phosphorylated neurofilament and aberrant
      activation of Cdk5 and GSK-3beta were detected in both pEGFP-peripherin and pINT
      EGFP cells by Western blotting. In addition, pharmacological approaches to
      retaining viability of pINT-EGFP and pEGFP-peripherin cells were examined.
      Treatment with Cdk5 inhibitor and GSK-3beta inhibitor significantly suppressed
      neuronal death. Dynamic changes of disaggregation of EGFP-peripherin and decrease
      in green fluorescence intensity were observed in pEGFP-peripherin and pINT-EGFP
      cells by confocal microscopy after GSK-3beta inhibitor treatment. We conclude
      that inhibition of Cdk5 and GSK-3beta suppresses neurofilament phosphorylation,
      slows down the accumulation of neuronal IF in the cytoplasm, and subsequently
      avoids damages to cell organelles. The results suggest that suppression of
      extensive neurofilament phosphorylation may be a potential strategy for
      ameliorating neuron death. The suppression of hyperphosphorylation of neuronal
      cytoskeletons with kinase inhibitors could be one of potential therapeutic
      treatments for neurodegenerative diseases.

PMID- 22952801
TI  - Validation of a measure of subjective well-being: an abbreviated version of the
      day reconstruction method.
AB  - BACKGROUND: The study of well-being is becoming a priority in social sciences.
      The Day Reconstruction Method (DRM) was developed to assess affective states. The
      aim of the present study was to validate an abbreviated version of the DRM
      designed for administration in population studies, and to assess its test-retest
      properties. PRINCIPAL FINDINGS: 1560 adults from Jodhpur (India) were interviewed
      using an abbreviated version of the DRM, and a week later they were re
      interviewed using the original long version of the DRM, after which the
      abbreviated version of the DRM was compared with the original version. A
      regression model considering interaction terms was employed to analyse the impact
      of sociodemographic characteristics on net affect. Test-retest reliability was
      assessed, and found to be moderate. Positive affect showed more test-retest
      reliability than negative affect, while net affect had more temporal stability
      than U-index. The affect of sets A, B, and C, taken together, had a moderate
      predictive ability compared with the affect obtained using the full version of
      the DRM: AUC = 0.67 for positive affect; 0.66 for net affect; 0.61 for negative
      affect; and 0.60 for the U-index. Household income, gender, and setting all had a
      significant impact on net affect. CONCLUSIONS: Net affect and positive affect
      showed moderate temporal stability, whereas negative affect and the U-index
      showed fair temporal stability. Evaluating the affective state using the
      abbreviated version of the DRM provides a profile of the population similar to
      that of the full version. The results provide considerable support for using the
      short version of the DRM as an instrument to measure subjective well-being in
      large population surveys.

PMID- 22952802
TI  - Evolution of multiple additive loci caused divergence between Drosophila yakuba
      and D. santomea in wing rowing during male courtship.
AB  - In Drosophila, male flies perform innate, stereotyped courtship behavior. This
      innate behavior evolves rapidly between fly species, and is likely to have
      contributed to reproductive isolation and species divergence. We currently
      understand little about the neurobiological and genetic mechanisms that
      contributed to the evolution of courtship behavior. Here we describe a novel
      behavioral difference between the two closely related species D. yakuba and D.
      santomea: the frequency of wing rowing during courtship. During courtship, D.
      santomea males repeatedly rotate their wing blades to face forward and then back
      (rowing), while D. yakuba males rarely row their wings. We found little
      intraspecific variation in the frequency of wing rowing for both species. We
      exploited multiplexed shotgun genotyping (MSG) to genotype two backcross
      populations with a single lane of Illumina sequencing. We performed quantitative
      trait locus (QTL) mapping using the ancestry information estimated by MSG and
      found that the species difference in wing rowing mapped to four or five
      genetically separable regions. We found no evidence that these loci display
      epistasis. The identified loci all act in the same direction and can account for
      most of the species difference.

PMID- 22952803
TI  - Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by
      regulating alpha7AChR, ERK, HIF-1alpha and VEGF/PEDF signaling.
AB  - Nicotine, the major component in cigarette smoke, can promote tumor growth and
      angiogenesis, but the precise mechanisms involved remain largely unknown. Here,
      we investigated the mechanism of action of nicotine in human nasopharyngeal
      carcinoma (NPC) cells. Nicotine significantly promoted cell proliferation in a
      dose and time-dependent manner in human NPC cells. The mechanism studies showed
      that the observed stimulation of proliferation was accompanied by the nicotine
      mediated simultaneous modulation of alpha7AChR, HIF-1alpha, ERK and VEGF/PEDF
      signaling. Treatment of NPC cells with nicotine markedly upregulated the
      expression of alpha7AChR and HIF-1alpha proteins. Transfection with a alpha7AChR
      or HIF-1alpha-specific siRNA or a alpha7AChR-selective inhibitor significantly
      attenuated the nicotine-mediated promotion of NPC cell proliferation. Nicotine
      also promoted the phosphorylation of ERK1/2 but not JNK and p38 proteins, thereby
      induced the activation of ERK/MAPK signaling pathway. Pretreatment with an ERK
      selective inhibitor effectively reduced the nicotine-induced proliferation of NPC
      cells. Moreover, nicotine upregulated the expression of VEGF but suppressed the
      expression of PEDF at mRNA and protein levels, leading to a significant increase
      of the ratio of VEGF/PEDF in NPC cells. Pretreatment with a alpha7AChR or ERK
      selective inhibitor or transfection with a HIF-1alpha-specific siRNA in NPC cells
      significantly inhibited the nicotine-induced HIF-1alpha expression and VEGF/PEDF
      ratio. These results therefore indicate that nicotine promotes proliferation of
      human NPC cells in vitro through simultaneous modulation of alpha7AChR, HIF
      1alpha, ERK and VEGF/PEDF signaling and suggest that the related molecules such
      as HIF-1alpha might be the potential therapeutic targets for tobacco-associated
      diseases such as nasopharyngeal carcinomas.

PMID- 22952804
TI  - Biphasic kinetic behavior of E. coli WrbA, an FMN-dependent NAD(P)H:quinone
      oxidoreductase.
AB  - The E. coli protein WrbA is an FMN-dependent NAD(P)H:quinone oxidoreductase that
      has been implicated in oxidative defense. Three subunits of the tetrameric enzyme
      contribute to each of four identical, cavernous active sites that appear to
      accommodate NAD(P)H or various quinones, but not simultaneously, suggesting an
      obligate tetramer with a ping-pong mechanism in which NAD departs before oxidized
      quinone binds. The present work was undertaken to evaluate these suggestions and
      to characterize the kinetic behavior of WrbA. Steady-state kinetics results
      reveal that WrbA conforms to a ping-pong mechanism with respect to the constancy
      of the apparent Vmax to Km ratio with substrate concentration. However, the
      competitive/non-competitive patterns of product inhibition, though consistent
      with the general class of bi-substrate reactions, do not exclude a minor
      contribution from additional forms of the enzyme. NMR results support the
      presence of additional enzyme forms. Docking and energy calculations find that
      electron-transfer-competent binding sites for NADH and benzoquinone present
      severe steric overlap, consistent with the ping-pong mechanism. Unexpectedly,
      plots of initial velocity as a function of either NADH or benzoquinone
      concentration present one or two Michaelis-Menten phases depending on the
      temperature at which the enzyme is held prior to assay. The effect of temperature
      is reversible, suggesting an intramolecular conformational process. WrbA shares
      these and other details of its kinetic behavior with mammalian DT-diaphorase, an
      FAD-dependent NAD(P)H:quinone oxidoreductase. An extensive literature review
      reveals several other enzymes with two-plateau kinetic plots, but in no case has
      a molecular explanation been elucidated. Preliminary sedimentation velocity
      analysis of WrbA indicates a large shift in size of the multimer with
      temperature, suggesting that subunit assembly coupled to substrate binding may
      underlie the two-plateau behavior. An additional aim of this report is to bring
      under wider attention the apparently widespread phenomenon of two-plateau
      Michaelis-Menten plots.

PMID- 22952806
TI  - Martharaptor greenriverensis, a new theropod dinosaur from the Lower Cretaceous
      of Utah.
AB  - BACKGROUND: The Yellow Cat Member of the Cedar Mountain Formation (Early
      Cretaceous, Barremian?) of Utah has yielded a rich dinosaur fauna, including the
      basal therizinosauroid theropod Falcarius utahensis at its base. Recent
      excavation uncovered a new possible therizinosauroid taxon from a higher
      stratigraphic level in the Cedar Mountain Formation than F. utahensis.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a fragmentary skeleton of the
      new theropod and perform a phylogenetic analysis to determine its phylogenetic
      position. The skeleton includes fragments of vertebrae, a scapula, forelimb and
      hindlimb bones, and an ischium. It also includes several well-preserved manual
      unguals. Manual and pedal morphology show that the specimen is distinct from
      other theropods from the Cedar Mountain Formation and from previously described
      therizinosauroids. It is here named as the holotype of a new genus and species,
      Martharaptor greenriverensis. Phylogenetic analysis places M. greenriverensis
      within Therizinosauroidea as the sister taxon to Alxasaurus + Therizinosauridae,
      although support for this placement is weak. CONCLUSIONS/SIGNIFICANCE: The new
      specimen adds to the known dinosaurian fauna of the Yellow Cat Member of the
      Cedar Mountain Formation. If the phylogenetic placement is correct, it also adds
      to the known diversity of Therizinosauroidea.

PMID- 22952805
TI  - Genome-wide association study of African and European Americans implicates
      multiple shared and ethnic specific loci in sarcoidosis susceptibility.
AB  - Sarcoidosis is a systemic inflammatory disease characterized by the formation of
      granulomas in affected organs. Genome-wide association studies (GWASs) of this
      disease have been conducted only in European population. We present the first
      sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls)
      followed by replication in independent sets of AAs (455 cases and 557 controls)
      and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6
      million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from
      the 1000 Genomes Project data. We identified a novel sarcoidosis-associated
      locus, NOTCH4, that reached genome-wide significance in the combined AA samples
      (rs715299, P(AA-meta) = 6.51 * 10(-10)) and demonstrated the independence of this
      locus from others in the MHC region in the same sample. We replicated previous
      European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11
      in both our AA and EA datasets. We also confirmed significant associations to the
      previously reported HLA-C and HLA-B regions in the EA but not AA samples. We
      further identified suggestive associations with several other genes previously
      reported in lung or inflammatory diseases.

PMID- 22952807
TI  - Phylogenetically-informed priorities for amphibian conservation.
AB  - The amphibian decline and extinction crisis demands urgent action to prevent
      further large numbers of species extinctions. Lists of priority species for
      conservation, based on a combination of species' threat status and unique
      contribution to phylogenetic diversity, are one tool for the direction and
      catalyzation of conservation action. We describe the construction of a near
      complete species-level phylogeny of 5713 amphibian species, which we use to
      create a list of evolutionarily distinct and globally endangered species (EDGE
      list) for the entire class Amphibia. We present sensitivity analyses to test the
      robustness of our priority list to uncertainty in species' phylogenetic position
      and threat status. We find that both sources of uncertainty have only minor
      impacts on our 'top 100' list of priority species, indicating the robustness of
      the approach. By contrast, our analyses suggest that a large number of Data
      Deficient species are likely to be high priorities for conservation action from
      the perspective of their contribution to the evolutionary history.

PMID- 22952808
TI  - Early invasion of brain parenchyma by African trypanosomes.
AB  - Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic
      disease that has a major impact on human health and welfare in sub-Saharan
      countries. Based mostly on data from animal models, it is currently thought that
      trypanosome entry into the brain occurs by initial infection of the choroid
      plexus and the circumventricular organs followed days to weeks later by entry
      into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly
      cross human brain microvascular endothelial cells in vitro and appear to be able
      to enter the murine brain without inflicting cerebral injury. Using a murine
      model and intravital brain imaging, we show that bloodstream forms of T. b.
      brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a
      significant level of microvascular inflammation is detectable. Extravascular
      bloodstream forms were viable as indicated by motility and cell division, and
      remained detectable for at least 3 days post infection suggesting the potential
      for parasite survival in the brain parenchyma. Vascular inflammation, as
      reflected by leukocyte recruitment and emigration from cortical microvessels,
      became apparent only with increasing parasitemia at later stages of the
      infection, but was not associated with neurological signs. Extravascular
      trypanosomes were predominantly associated with postcapillary venules suggesting
      that early brain infection occurs by parasite passage across the
      neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine
      brain parenchyma during the early stages of the disease before
      meningoencephalitis is fully established. Whether individual trypanosomes can act
      alone or require the interaction from a quorum of parasites remains to be shown.
      The significance of these findings for disease development is now testable.

PMID- 22952809
TI  - PR3 and elastase alter PAR1 signaling and trigger vWF release via a calcium
      independent mechanism from glomerular endothelial cells.
AB  - Neutrophil proteases, proteinase-3 (PR3) and elastase play key roles in
      glomerular endothelial cell (GEC) injury during glomerulonephritis. Endothelial
      protease-activated receptors (PARs) are potential serine protease targets in
      glomerulonephritis. We investigated whether PAR1/2 are required for alterations
      in GEC phenotype that are mediated by PR3 or elastase during active
      glomerulonephritis. Endothelial PARs were assessed by flow cytometry. Thrombin,
      trypsin and agonist peptides for PAR1 and PAR2, TFLLR-NH(2) and SLIGKV-NH(2,)
      respectively, were used to assess alterations in PAR activation induced by PR3 or
      elastase. Endothelial von Willebrand Factor (vWF)release and calcium signaling
      were used as PAR activation markers. Both PR3 and elastase induced endothelial
      vWF release, with elastase inducing the highest response. PAR1 peptide induced
      GEC vWF release to the same extent as PR3. However, knockdown of PARs by small
      interfering RNA showed that neither PAR1 nor PAR2 activation caused PR3 or
      elastase-mediated vWF release. Both proteases interacted with and disarmed
      surface GEC PAR1, but there was no detectable interaction with cellular PAR2.
      Neither protease induced a calcium response in GEC. Therefore, PAR signaling and
      serine protease-induced alterations in endothelial function modulate glomerular
      inflammation via parallel but independent pathways.

PMID- 22952810
TI  - Socioeconomic and environmental risk factors among rheumatic heart disease
      patients in Uganda.
AB  - BACKGROUND: Although low socioeconomic status, and environmental factors are
      known risk factors for rheumatic heart disease in other societies, risk factors
      for rheumatic heart disease remain less well described in Uganda. AIMS AND
      OBJECTIVE: The objective of this study was to investigate the role of socio
      economic and environmental factors in the pathogenesis of rheumatic heart disease
      in Ugandan patients. METHODS: This was a case control study in which rheumatic
      heart disease cases and normal controls aged 5-60 years were recruited and
      investigated for socioeconomic and environmental risk factors such as income
      status, employment status, distance from the nearest health centre, number of
      people per house and space area per person. RESULTS: 486 participants (243 cases
      and 243 controls) took part in the study. Average age was 32.37+/-14.6 years for
      cases and 35.75+/-12.6 years for controls. At univariate level, Cases tended to
      be more overcrowded than controls; 8.0+/-3.0 versus 6.0+/-3.0 persons per house.
      Controls were better spaced at 25.2 square feet versus 16.9 for cases. More
      controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to
      health centers than the cases; 4.8+/-3.8 versus 3.3+/-12.9 kilometers. At
      multivariate level, the odds of rheumatic heart disease was 1.7 times higher for
      unemployment status (OR = 1.7, 95% CI = 1.05-8.19) and 1.3 times higher for
      overcrowding (OR = 1.35, 95% CI = 1.1-1.56). There was interaction between
      overcrowding and longer distance from the nearest health centre (OR = 1.20, 95%
      CI = 1.05-1.42). CONCLUSION: The major findings of this study were that there was
      a trend towards increased risk of rheumatic heart disease in association with
      overcrowding and unemployment. There was interaction between overcrowding and
      distance from the nearest health center, suggesting that the effect of
      overcrowding on the risk of acquiring rheumatic heart disease increases with
      every kilometer increase from the nearest health center.

PMID- 22952811
TI  - Involvement of microglia activation in the lead induced long-term potentiation
      impairment.
AB  - Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and
      memory probably via impairing the hippocampal long-term potentiation (LTP) as
      well as hippocampal neuronal injury. Activation of hippocampal microglia also
      impairs spatial learning and memory. Thus, we raised the hypothesis that
      activation of microglia is involved in the Pb exposure induced hippocampal LTP
      impairment and neuronal injury. To test this hypothesis and clarify its
      underlying mechanisms, we investigated the Pb-exposure on the microglia
      activation, cytokine release, hippocampal LTP level as well as neuronal injury in
      in vivo or in vitro model. The changes of these parameters were also observed
      after pretreatment with minocycline, a microglia activation inhibitor. Long-term
      low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in
      acute slice preparations, meanwhile, such treatment also significantly increased
      hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure
      also induced significantly increase of microglia activation, up-regulate the
      release of cytokines including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in
      microglia culture alone as well as neuronal injury in the co-culture with
      hippocampal neurons. Inhibiting the microglia activation with minocycline
      significantly reversed the above-mentioned Pb-exposure induced changes. Our
      results showed that Pb can cause microglia activation, which can up-regulate the
      level of IL-1beta, TNF-alpha and iNOS, these proinflammatory factors may cause
      hippocampal neuronal injury as well as LTP deficits.

PMID- 22952812
TI  - Ratio between negative and positive lymph nodes is suitable for evaluation the
      prognosis of gastric cancer patients with positive node metastasis.
AB  - OBJECTIVE: To date, there is no consensus to evaluate the most appropriate
      category of the nodal metastasis for precise predication the prognosis of gastric
      cancer patients with positive node metastasis after curative surgery. METHODS: We
      retrospectively analyzed the clinicopathologic characteristics and overall
      survival (OS) of 299 gastric cancer patients with positive node metastasis after
      curative surgery for evaluation the optimal category of the nodal metastasis.
      RESULTS: With the univariate and multivariate survival analyses, the depth of
      primary tumor invasion was identified as the independent predicators with the OS
      of 299 gastric cancer patients with nodal metastasis postoperatively, as were the
      number of positive lymph nodes (PLNs), the number of negative lymph nodes (NLNs),
      and the ratio between negative and positive lymph nodes (RNPL). The RNPL was
      identified to be more suitable for predication the OS of gastric cancer patients
      with positive node metastasis than the ratio between positive and dissected lymph
      nodes (RPDL) by using the stratum procedure of survival analysis. Besides, we
      found both PLNs and NLNs were independently correlated with OS of gastric cancer
      patients with nodal metastasis when RNPL, instead of RPDL, was controlled in the
      partial correlation model. CONCLUSIONS: RNPL, a new category of the nodal
      metastasis, was suitable for predication the OS of gastric cancer patients with
      nodal metastasis after curative resection, as were the PLNs, and NLNs.

PMID- 22952813
TI  - A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob
      disease.
AB  - The beta site APP cleaving enzyme 1 (BACE1) is the rate-limiting beta-secretase
      enzyme in the amyloidogenic processing of APP and Abeta formation, and therefore
      it has a prominent role in Alzheimer's disease (AD) pathology. Recent evidence
      suggests that the prion protein (PrP) interacts directly with BACE1 regulating
      its beta-secretase activity. Moreover, PrP has been proposed as the cellular
      receptor involved in the impairment of synaptic plasticity and toxicity caused by
      Abeta oligomers. Provided that common pathophysiologic mechanisms are shared by
      Alzheimer's and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first
      time to the best of our knowledge a possible association of a common synonymous
      BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that
      BACE1 C-allele is associated with an increased risk for developing sCJD, mainly
      in PRNP M129M homozygous subjects with early onset. These results extend the very
      short list of genes (other than PRNP) involved in the development of human prion
      diseases; and support the notion that similar to AD, in sCJD several loci may
      contribute with modest overall effects to disease risk. These findings underscore
      the interplay in both pathologies of APP, Abeta oligomers, ApoE, PrP and BACE1,
      and suggest that aging and perhaps vascular risk factors may modulate disease
      pathologies in part through these key players.

PMID- 22952814
TI  - Nutrient presses and pulses differentially impact plants, herbivores,
      detritivores and their natural enemies.
AB  - Anthropogenic nutrient inputs into native ecosystems cause fluctuations in
      resources that normally limit plant growth, which has important consequences for
      associated food webs. Such inputs from agricultural and urban habitats into
      nearby natural systems are increasing globally and can be highly variable,
      spanning the range from sporadic to continuous. Despite the global increase in
      anthropogenically-derived nutrient inputs into native ecosystems, the
      consequences of variation in subsidy duration on native plants and their
      associated food webs are poorly known. Specifically, while some studies have
      examined the effects of nutrient subsidies on native ecosystems for a single year
      (a nutrient pulse), repeated introductions of nutrients across multiple years (a
      nutrient press) better reflect the persistent nature of anthropogenic nutrient
      enrichment. We therefore contrasted the effects of a one-year nutrient pulse with
      a four-year nutrient press on arthropod consumers in two salt marshes. Salt
      marshes represent an ideal system to address the differential impacts of nutrient
      pulses and presses on ecosystem and community dynamics because human development
      and other anthropogenic activities lead to recurrent introductions of nutrients
      into these natural systems. We found that plant biomass and %N as well as
      arthropod density fell after the nutrient pulse ended but remained elevated
      throughout the nutrient press. Notably, higher trophic levels responded more
      strongly than lower trophic levels to fertilization, and the predator/prey ratio
      increased each year of the nutrient press, demonstrating that food web responses
      to anthropogenic nutrient enrichment can take years to fully manifest themselves.
      Vegetation at the two marshes also exhibited an apparent tradeoff between
      increasing %N and biomass in response to fertilization. Our research emphasizes
      the need for long-term, spatially diverse studies of nutrient enrichment in order
      to understand how variation in the duration of anthropogenic nutrient subsidies
      affects native ecosystems.

PMID- 22952815
TI  - Influence of target concentration and background binding on in vitro selection of
      affinity reagents.
AB  - Nucleic acid-based aptamers possess many useful features that make them a
      promising alternative to antibodies and other affinity reagents, including well
      established chemical synthesis, reversible folding, thermal stability and low
      cost. However, the selection process typically used to generate aptamers (SELEX)
      often requires significant resources and can fail to yield aptamers with
      sufficient affinity and specificity. A number of seminal theoretical models and
      numerical simulations have been reported in the literature offering insights into
      experimental factors that govern the effectiveness of the selection process.
      Though useful, these previous models have not considered the full spectrum of
      experimental factors or the potential impact of tuning these parameters at each
      round over the course of a multi-round selection process. We have developed an
      improved mathematical model to address this important question, and report that
      both target concentration and the degree of non-specific background binding are
      critical determinants of SELEX efficiency. Although smaller target concentrations
      should theoretically offer superior selection outcome, we show that the level of
      background binding dramatically affect the target concentration that will yield
      maximum enrichment at each round of selection. Thus, our model enables
      experimentalists to determine appropriate target concentrations as a means for
      protocol optimization. Finally, we perform a comparative analysis of two
      different selection methods over multiple rounds of selection, and show that
      methods with inherently lower background binding offer dramatic advantages in
      selection efficiency.

PMID- 22952816
TI  - Land cover change in Colombia: surprising forest recovery trends between 2001 and
      2010.
AB  - BACKGROUND: Monitoring land change at multiple spatial scales is essential for
      identifying hotspots of change, and for developing and implementing policies for
      conserving biodiversity and habitats. In the high diversity country of Colombia,
      these types of analyses are difficult because there is no consistent wall-to
      wall, multi-temporal dataset for land-use and land-cover change.
      METHODOLOGY/PRINCIPAL FINDINGS: To address this problem, we mapped annual land
      use and land-cover from 2001 to 2010 in Colombia using MODIS (250 m) products
      coupled with reference data from high spatial resolution imagery (QuickBird) in
      Google Earth. We used QuickBird imagery to visually interpret percent cover of
      eight land cover classes used for classifier training and accuracy assessment.
      Based on these maps we evaluated land cover change at four spatial scales
      country, biome, ecoregion, and municipality. Of the 1,117 municipalities, 820 had
      a net gain in woody vegetation (28,092 km(2)) while 264 had a net loss (11,129
      km(2)), which resulted in a net gain of 16,963 km(2) in woody vegetation at the
      national scale. Woody regrowth mainly occurred in areas previously classified as
      mixed woody/plantation rather than agriculture/herbaceous. The majority of this
      gain occurred in the Moist Forest biome, within the montane forest ecoregions,
      while the greatest loss of woody vegetation occurred in the Llanos and Apure
      Villavicencio ecoregions. CONCLUSIONS: The unexpected forest recovery trend,
      particularly in the Andes, provides an opportunity to expand current protected
      areas and to promote habitat connectivity. Furthermore, ecoregions with intense
      land conversion (e.g. Northern Andean Paramo) and ecoregions under-represented in
      the protected area network (e.g. Llanos, Apure-Villavicencio Dry forest, and
      Magdalena-Uraba Moist forest ecoregions) should be considered for new protected
      areas.

PMID- 22952817
TI  - Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and
      Kv1.3 channel.
AB  - Increasing evidence supports a critical role of T cells in neurodegeneration
      associated with acute and subacute brain inflammatory disorders. Granzyme B
      (GrB), released by activated T cells, is a cytotoxic proteinase which may induce
      perforin-independent neurotoxicity. Here, we studied the mechanism of perforin
      independent GrB toxicity by treating primary cultured human neuronal cells with
      recombinant GrB. GrBactivated the protease-activated receptor (PAR)-1 receptor on
      the neuronal cell surface leading to decreased intracellular cyclic AMP levels.
      This was followed by increased expression and translocation of the voltage gated
      potassium channel, Kv1.3 to the neuronal cell membrane. Similar expression of
      Kv1.3 was also seen in neurons of the cerebral cortex adjacent to active
      inflammatory lesions in patients with multiple sclerosis. Kv1.3 expression was
      followed by activation of Notch-1 resulting in neurotoxicity. Blocking PAR-1,
      Kv1.3 or Notch-1 activation using specific pharmacological inhibitors or siRNAs
      prevented GrB-induced neurotoxicity. Furthermore, clofazimine protected against
      GrB-induced neurotoxicity in rat hippocampus, in vivo. These observations
      indicate that GrB released from T cells induced neurotoxicity by interacting with
      the membrane bound Gi-coupled PAR-1 receptor and subsequently activated Kv1.3 and
      Notch-1. These pathways provide novel targets to treat T cell-mediated
      neuroinflammatory disorders. Kv1.3 is of particular interest since it is
      expressed on the cell surface, only under pathological circumstances, and early
      in the cascade of events making it an attractive therapeutic target.

PMID- 22952818
TI  - Searching for lower female genital tract soluble and cellular biomarkers:
      defining levels and predictors in a cohort of healthy Caucasian women.
AB  - BACKGROUND: High concentrations of pro-inflammatory cytokines have been
      previously observed in the genital fluids of women enrolled in microbicide trials
      and may explain observed increased HIV transmission in some of these trials.
      Although the longitudinal nature of these studies allows within-subject
      comparisons of post-product levels to baseline levels, the fact that the
      physiologic variations of these cytokines and other markers of immune activation
      are not fully defined in different populations, makes it difficult to assess
      changes that can be directly attributed to microbicide use as opposed to other
      biological and behavioural factors. METHODS: Cervicovaginal lavage samples were
      collected from 30 healthy Caucasian and assayed for concentrations of ten
      cytokines/chemokines, total protein content and two antimicrobial proteins using
      a multiplex immunoassay and ELISA. Cellular markers were characterized by flow
      cytometry on mononuclear cells collected from the endocervix using flocked swabs.
      Bacterial quantification was performed using quantitative PCR. RESULTS: Ectopy,
      menstrual cycle phase, prostate-specific antigen and presence of leucocytes in
      endocervical cells' supernatant were associated with the concentrations of cyto
      /chemokines in cervicovaginal secretions. Approximately 3% of endocervical cells
      collected were monocytes of which a median of 52% (SD  = 17) expressed both CD4
      and CCR5 markers. Approximately 1% of the total cells were T-cells with a median
      of 61% (SD  = 10) CD4 and CCR5 expression. Around 5% of the monocytes and 16% of
      the T-cells expressed the immune activation marker HLA-DR. Higher percentages of
      T-cells were associated with greater quantities of IL-1RA, GM-CSF and elafin.
      CONCLUSION: We demonstrate the presence of selected soluble and cellular immune
      activation markers and identify their predictors in the female genital tract of
      healthy women. Future clinical trials should consider ectopy, sexual activity,
      menstrual cycle phase and presence of bacterial species as possible confounders
      when evaluating the possible inflammatory effects of microbicide compounds.

PMID- 22952819
TI  - Mortality after fluid bolus in children with shock due to sepsis or severe
      infection: a systematic review and meta-analysis.
AB  - INTRODUCTION: Sepsis is one of the leading causes of childhood mortality, yet
      controversy surrounds the current treatment approach. We conducted a systematic
      review to assess the evidence base for fluid resuscitation in the treatment of
      children with shock due to sepsis or severe infection. METHODS: We searched 3
      databases for randomized trials, quasi-randomized trials, and controlled before
      after studies assessing children with septic shock in which at least one group
      was treated with bolus fluids. The primary outcome was mortality at 48 hours.
      Assessment of methodological quality followed the GRADE criteria. Relative risks
      (RRs) and 95% confidence intervals (CI) were calculated and data pooled using
      fixed-effects method. RESULTS: 13 studies met our inclusion criteria. No bolus
      has significantly better mortality outcomes at 48 hours for children with general
      septic shock (RR 0.69; 95%CI 0.54-0.89), and children with malaria (RR 0.64;
      95%CI 0.45-0.91) when compared to giving any bolus. This result is largely driven
      by a single, high quality trial (the FEAST trial). There is no evidence
      investigating bolus vs no bolus in children with Dengue fever or severe
      malnutrition. Colloid and crystalloid boluses were found to have similar effects
      on mortality across all sub-groups (general septic shock, malaria, Dengue fever,
      and severe malnutrition). CONCLUSIONS: The majority of all randomized evidence to
      date comes from the FEAST trial, which found that fluid boluses were harmful
      compared to no bolus. Simple algorithms are needed to support health-care
      providers in the triage of patients to determine who could potentially be harmed
      by the provision of bolus fluids, and who will benefit.

PMID- 22952820
TI  - Modeling pathogenic mutations of human twinkle in Drosophila suggests an
      apoptosis role in response to mitochondrial defects.
AB  - The human gene C10orf2 encodes the mitochondrial replicative DNA helicase
      Twinkle, mutations of which are responsible for a significant fraction of cases
      of autosomal dominant progressive external ophthalmoplegia (adPEO), a human
      mitochondrial disease caused by defects in intergenomic communication. We report
      the analysis of orthologous mutations in the Drosophila melanogaster
      mitochondrial DNA (mtDNA) helicase gene, d-mtDNA helicase. Increased expression
      of wild type d-mtDNA helicase using the UAS-GAL4 system leads to an increase in
      mtDNA copy number throughout adult life without any noteworthy phenotype, whereas
      overexpression of d-mtDNA helicase containing the K388A mutation in the helicase
      active site results in a severe depletion of mtDNA and a lethal phenotype.
      Overexpression of two d-mtDNA helicase variants equivalent to two human adPEO
      mutations shows differential effects. The A442P mutation exhibits a dominant
      negative effect similar to that of the active site mutant. In contrast,
      overexpression of d-mtDNA helicase containing the W441C mutation results in a
      slight decrease in mtDNA copy number during the third instar larval stage, and a
      moderate decrease in life span in the adult population. Overexpression of d-mtDNA
      helicase containing either the K388A or A442P mutations causes a mitochondrial
      oxidative phosphorylation (OXPHOS) defect that significantly reduces cell
      proliferation. The mitochondrial impairment caused by these mutations promotes
      apoptosis, arguing that mitochondria regulate programmed cell death in
      Drosophila. Our study of d-mtDNA helicase overexpression provides a tractable
      Drosophila model for understanding the cellular and molecular effects of human
      adPEO mutations.

PMID- 22952821
TI  - Establishment of mouse teratocarcinomas stem cells line and screening genes
      responsible for malignancy.
AB  - The sequential transplantation of embryonal carcinoma cells in vivo can
      accelerate the growth and malignancy of teratocarcinomas. However, the possible
      molecular mechanisms in this process that reflect cancer formation in the early
      stage are largely unknown and. To identify which genes are associated with the
      changes of malignancy of teratocarcinomas, we established a tumorigenesis model
      in which teratocarcinoma were induced via injecting embryonic stem cells into
      immuno-deficiency mice, isolating teratocarcinoma stem cell from a
      teratocarcinoma in serum-free culture medium and injecting teratocarcinoma stem
      cells into immune-deficient mice continuously. By using high-throughput deep
      sequence technology, we identified 26 differentially expressed genes related to
      the changes of characteristics of teratocarcinoma stem cell in which 18 out of 26
      genes were down-regulated and 8 genes were up-regulated. Among these genes,
      several tumor-related genes such as Gata3, Arnt and Tdgf1, epigenetic associated
      genes such as PHC1 and Uty were identified. Pathway enrichment analysis result
      revealed that Wnt signaling pathway, primary immunodeficiency pathway, antigen
      processing and presentation pathway and allograft rejection pathway were involved
      in the teratocarcinoma tumorigenesis (corrected p value<0.05). In summary, our
      study established a tumorigenesis model and proposed some candidate genes and
      signaling pathways that may play a key role in the early stage of cancer
      occurrence.

PMID- 22952822
TI  - A novel role for the transcription factor Cwt1p as a negative regulator of
      nitrosative stress in Candida albicans.
AB  - The ability of Candida albicans to survive in the presence of nitrosative stress
      during the initial contact with the host immune system is crucial for its ability
      to colonize mammalian hosts. Thus, this fungus must activate robust mechanisms to
      neutralize and repair nitrosative-induced damage. Until now, very little was
      known regarding the regulatory circuits associated with reactive nitrogen species
      detoxification in fungi. To gain insight into the transcriptional regulatory
      networks controlling nitrosative stress response (NRS) in C. albicans a
      compilation of transcriptional regulator-defective mutants were screened. This
      led to the identification of Cwt1p as a negative regulator of NSR. By combining
      genome-wide location and expression analyses, we have characterized the Cwt1p
      regulon and demonstrated that Cwt1p is directly required for proper repression of
      the flavohemoglobin Yhb1p, a key NO-detoxification enzyme. Furthermore, Cwt1p
      operates both by activating and repressing genes of specific functions solicited
      upon NSR. Additionally, we used Gene Set Enrichment Analysis to reinvestigate the
      C. albicans NSR-transcriptome and demonstrate a significant similarity with the
      transcriptional profiles of C. albicans interacting with phagocytic host-cells.
      In summary, we have characterized a novel negative regulator of NSR and bring new
      insights into the transcriptional regulatory network governing fungal NSR.

PMID- 22952823
TI  - Theta oscillations are sensitive to both early and late conflict processing
      stages: effects of alcohol intoxication.
AB  - Prior neuroimaging evidence indicates that decision conflict activates medial and
      lateral prefrontal and parietal cortices. Theoretical accounts of cognitive
      control highlight anterior cingulate cortex (ACC) as a central node in this
      network. However, a better understanding of the relative primacy and functional
      contributions of these areas to decision conflict requires insight into the
      neural dynamics of successive processing stages including conflict detection,
      response selection and execution. Moderate alcohol intoxication impairs cognitive
      control as it interferes with the ability to inhibit dominant, prepotent
      responses when they are no longer correct. To examine the effects of moderate
      intoxication on successive processing stages during cognitive control, spatio
      temporal changes in total event-related theta power were measured during Stroop
      induced conflict. Healthy social drinkers served as their own controls by
      participating in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg women) and
      placebo conditions in a counterbalanced design. Anatomically-constrained
      magnetoencephalography (aMEG) approach was applied to complex power spectra for
      theta (4-7 Hz) frequencies. The principal generator of event-related theta power
      to conflict was estimated to ACC, with contributions from fronto-parietal areas.
      The ACC was uniquely sensitive to conflict during both early conflict detection,
      and later response selection and execution stages. Alcohol attenuated theta power
      to conflict across successive processing stages, suggesting that alcohol-induced
      deficits in cognitive control may result from theta suppression in the executive
      network. Slower RTs were associated with attenuated theta power estimated to ACC,
      indicating that alcohol impairs motor preparation and execution subserved by the
      ACC. In addition to their relevance for the currently prevailing accounts of
      cognitive control, our results suggest that alcohol-induced impairment of top
      down strategic processing underlies poor self-control and inability to refrain
      from drinking.

PMID- 22952824
TI  - Daptomycin resistance in enterococci is associated with distinct alterations of
      cell membrane phospholipid content.
AB  - BACKGROUND: The lipopeptide antibiotic, daptomycin (DAP) interacts with the
      bacterial cell membrane (CM). Development of DAP resistance during therapy in a
      clinical strain of Enterococcus faecalis was associated with mutations in genes
      encoding enzymes involved in cell envelope homeostasis and phospholipid
      metabolism. Here we characterized changes in CM phospholipid profiles associated
      with development of DAP resistance in clinical enterococcal strains. METHODOLOGY:
      Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis
      (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP
      therapy, we compared four distinct CM profiles: phospholipid content, fatty acid
      composition, membrane fluidity and capacity to be permeabilized and/or
      depolarized by DAP. Additionally, we characterized the cell envelope of the E.
      faecium strain-pair by transmission electron microscopy and determined the
      relative cell surface charge of both strain-pairs. PRINCIPAL FINDINGS: Both E.
      faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol
      (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho
      diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E.
      faecium) also contained: i) phosphatidic acid; and ii) two other unknown species
      of amino-containing PLs. Development of DAP resistance in both enterococcal
      species was associated with a significant decrease in CM fluidity and PG content,
      with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their
      outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did
      not change in the E. faecalis strain-pair, whereas a significant decrease in
      unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446
      (vs S447). Resistance to DAP in E. faecium was associated with distinct
      structural alterations of the cell envelope and cell wall thickening, as well as
      a decreased ability of DAP to depolarize and permeabilize the CM. CONCLUSION:
      Distinct alterations in PL content and fatty acid composition are associated with
      development of enterococcal DAP resistance.

PMID- 22952825
TI  - Beta cell count instead of beta cell mass to assess and localize growth in beta
      cell population following pancreatic duct ligation in mice.
AB  - BACKGROUND: Pancreatic-tail duct ligation (PDL) in adult rodents has been
      reported to induce beta cell generation and increase beta cell mass but increases
      in beta cell number have not been demonstrated. This study examines whether PDL
      increases beta cell number and whether this is caused by neogenesis of small
      clusters and/or their growth to larger aggregates. METHODOLOGY: Total beta cell
      number and its distribution over small (<50 um), medium, large (>100 um) clusters
      was determined in pancreatic tails of 10-week-old mice, 2 weeks after PDL or
      sham. PRINCIPAL FINDINGS: PDL increased total beta cell mass but not total beta
      cell number. It induced neogenesis of small beta cell clusters (2.2-fold higher
      number) which contained a higher percent proliferating beta cells (1.9%
      Ki67+cells) than sham tails (<0.2%); their higher beta cell number represented
      <5% of total beta cell number and was associated with a similar increase in alpha
      cell number. It is unknown whether the regenerative process is causally related
      to the inflammatory infiltration in PDL-tails. Human pancreases with inflammatory
      infiltration also exhibited activation of proliferation in small beta cell
      clusters. CONCLUSIONS/SIGNIFICANCE: The PDL model illustrates the advantage of
      direct beta cell counts over beta cell mass measurements when assessing and
      localizing beta cell regeneration in the pancreas. It demonstrates the ability of
      the adult mouse pancreas for neogenesis of small beta cell clusters with
      activated beta cell proliferation. Further studies should investigate conditions
      under which neoformed small beta cell clusters grow to larger aggregates and
      hence to higher total beta cell numbers.

PMID- 22952826
TI  - Tissue specific induction of p62/Sqstm1 by farnesoid X receptor.
AB  - BACKGROUND: Farnesoid X Receptor (FXR) is a member of the nuclear receptor
      superfamily and is a ligand-activated transcription factor essential for
      maintaining liver and intestinal homeostasis. FXR is protective against
      carcinogenesis and inflammation in liver and intestine as demonstrated by the
      development of inflammation and tumors in the liver and intestine of FXR knock
      out mice. However, mechanisms for the protective effects of FXR are not
      completely understood. This study reports a novel role of FXR in regulating
      expression of Sqstm1, which encodes for p62 protein. p62 plays an important role
      in maintaining cellular homeostasis through selective autophagy and activating
      signal transduction pathways, such as NF-kappaB to support cell survival and
      caspase-8 to initiate apoptosis. FXR regulation of Sqstm1 may serve as a
      protective mechanism. METHODS AND RESULTS: This study showed that FXR bound to
      the Sqstm1 gene in both mouse livers and ileums as determined by chromatin
      immunoprecipitation. In addition, FXR activation enhanced transcriptional
      activation of Sqstm1 in vitro. However, wild-type mice treated with GW4064, a
      synthetic FXR ligand, showed that FXR activation induced mRNA and protein
      expression of Sqstm1/p62 in ileum, but not in liver. Interestingly, FXR
      transgenic mice showed induced mRNA expression of Sqstm1 in both liver and ileum
      compared to wild-type mice. CONCLUSIONS: Our current study has identified a novel
      role of FXR in regulating the expression of p62, a key factor in protein
      degradation and cell signaling. Regulation of p62 by FXR indicates tissue
      specific and gene-dosage effects. Furthermore, FXR-mediated induction of p62 may
      implicate a protective mechanism of FXR.

PMID- 22952827
TI  - Influence of methylene blue on microglia-induced inflammation and motor neuron
      degeneration in the SOD1(G93A) model for ALS.
AB  - Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease
      amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell
      autonomous, with toxicity deriving also from glia. In particular, microglia
      contribute to disease progression. Methylene blue (MB) inhibits the effect of
      nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM
      imaging was performed in ALS-linked transgenic SOD1(G93A) mice to investigate the
      effect of MB on microglia-mediated inflammation in the spinal cord. Local
      superfusion of the lateral spinal cord with MB inhibited the microglial reaction
      directed at a laser-induced axon transection in control and SOD1(G93A) mice. In
      vitro, MB at high concentrations inhibited cytokine and chemokine release from
      microglia of control and advanced clinical SOD1(G93A) mice. Systemic MB-treatment
      of SOD1(G93A) mice at early preclinical stages significantly delayed disease
      onset and motor dysfunction. However, an increase of MB dose had no additional
      effect on disease progression; this was unexpected in view of the local anti
      inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated
      mice also showed no alterations of microglia activity in response to local
      lesions. Thus although systemic MB treatment had no effect on microgliosis,
      instead, its use revealed an important influence on motor neuron survival as
      indicated by an increased number of lumbar anterior horn neurons present at the
      time of disease onset. Thus, potentially beneficial effects of locally applied MB
      on inflammatory events contributing to disease progression could not be
      reproduced in SOD1(G93A) mice via systemic administration, whereas systemic MB
      application delayed disease onset via neuroprotection.

PMID- 22952828
TI  - The relationship between respiration-related membrane potential slow oscillations
      and discharge patterns in mitral/tufted cells: what are the rules?
AB  - BACKGROUND: A slow respiration-related rhythm strongly shapes the activity of the
      olfactory bulb. This rhythm appears as a slow oscillation that is detectable in
      the membrane potential, the respiration-related spike discharge of the
      mitral/tufted cells and the bulbar local field potential. Here, we investigated
      the rules that govern the manifestation of membrane potential slow oscillations
      (MPSOs) and respiration-related discharge activities under various afferent input
      conditions and cellular excitability states. METHODOLOGY AND PRINCIPAL FINDINGS:
      We recorded the intracellular membrane potential signals in the mitral/tufted
      cells of freely breathing anesthetized rats. We first demonstrated the existence
      of multiple types of MPSOs, which were influenced by odor stimulation and
      discharge activity patterns. Complementary studies using changes in the
      intracellular excitability state and a computational model of the mitral cell
      demonstrated that slow oscillations in the mitral/tufted cell membrane potential
      were also modulated by the intracellular excitability state, whereas the
      respiration-related spike activity primarily reflected the afferent input. Based
      on our data regarding MPSOs and spike patterns, we found that cells exhibiting an
      unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with
      a respiration-synchronized discharge pattern always exhibited an MPSO. In
      addition, we demonstrated that the association between spike patterns and MPSO
      types appeared complex. CONCLUSION: We propose that both the intracellular
      excitability state and input strength underlie specific MPSOs, which, in turn,
      constrain the types of spike patterns exhibited.

PMID- 22952829
TI  - Kinetic modelling of GlmU reactions - prioritization of reaction for therapeutic
      application.
AB  - Mycobacterium tuberculosis(Mtu), a successful pathogen, has developed resistance
      against the existing anti-tubercular drugs necessitating discovery of drugs with
      novel action. Enzymes involved in peptidoglycan biosynthesis are attractive
      targets for antibacterial drug discovery. The bifunctional enzyme mycobacterial
      GlmU (Glucosamine 1-phosphate N-acetyltransferase/ N-acetylglucosamine-1
      phosphate uridyltransferase) has been a target enzyme for drug discovery. Its C-
      and N- terminal domains catalyze acetyltransferase (rxn-1) and uridyltransferase
      (rxn-2) activities respectively and the final product is involved in
      peptidoglycan synthesis. However, the bifunctional nature of GlmU poses
      difficulty in deciding which function to be intervened for therapeutic advantage.
      Genetic analysis showed this as an essential gene but it is still unclear whether
      any one or both of the activities are critical for cell survival. Often enzymatic
      activity with suitable high-throughput assay is chosen for random screening,
      which may not be the appropriate biological function inhibited for maximal
      effect. Prediction of rate-limiting function by dynamic network analysis of
      reactions could be an option to identify the appropriate function. With a view to
      provide insights into biochemical assays with appropriate activity for inhibitor
      screening, kinetic modelling studies on GlmU were undertaken. Kinetic model of
      Mtu GlmU-catalyzed reactions was built based on the available kinetic data on Mtu
      and deduction from Escherichia coli data. Several model variants were constructed
      including coupled/decoupled, varying metabolite concentrations and
      presence/absence of product inhibitions. This study demonstrates that in coupled
      model at low metabolite concentrations, inhibition of either of the GlmU
      reactions cause significant decrement in the overall GlmU rate. However at higher
      metabolite concentrations, rxn-2 showed higher decrement. Moreover, with
      available intracellular concentration of the metabolites and in vivo variant of
      model, uncompetitive inhibition of rxn-2 caused highest decrement. Thus, at
      physiologically relevant metabolite concentrations, targeting uridyltranferase
      activity of Mtu GlmU would be a better choice for therapeutic intervention.

PMID- 22952830
TI  - Extensive pyrosequencing reveals frequent intra-genomic variations of internal
      transcribed spacer regions of nuclear ribosomal DNA.
AB  - BACKGROUND: Internal transcribed spacer of nuclear ribosomal DNA (nrDNA) is
      already one of the most popular phylogenetic and DNA barcoding markers. However,
      the existence of its multiple copies has complicated such usage and a detailed
      characterization of intra-genomic variations is critical to address such
      concerns. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used sequence-tagged
      pyrosequencing and genome-wide analyses to characterize intra-genomic variations
      of internal transcribed spacer 2 (ITS2) regions from 178 plant species. We
      discovered that mutation of ITS2 is frequent, with a mean of 35 variants per
      species. And on average, three of the most abundant variants make up 91% of all
      ITS2 copies. Moreover, we found different congeneric species share identical
      variants in 13 genera. Interestingly, different species across different genera
      also share identical variants. In particular, one minor variant of ITS2 in
      Eleutherococcus giraldii was found identical to the ITS2 major variant of Panax
      ginseng, both from Araliaceae family. In addition, DNA barcoding gap analysis
      showed that the intra-genomic distances were markedly smaller than those of the
      intra-specific or inter-specific variants. When each of 5543 variants were
      examined for its species discrimination efficiency, a 97% success rate was
      obtained at the species level. CONCLUSIONS: Identification of identical ITS2
      variants across intra-generic or inter-generic species revealed complex species
      evolutionary history, possibly, horizontal gene transfer and ancestral
      hybridization. Although intra-genomic multiple variants are frequently found
      within each genome, the usage of the major variants alone is sufficient for
      phylogeny construction and species determination in most cases. Furthermore, the
      inclusion of minor variants further improves the resolution of species
      identification.

PMID- 22952831
TI  - Antibody constant region peptides can display immunomodulatory activity through
      activation of the Dectin-1 signalling pathway.
AB  - We previously reported that a synthetic peptide with sequence identical to a CDR
      of a mouse monoclonal antibody specific for difucosyl human blood group A exerted
      an immunomodulatory activity on murine macrophages. It was therapeutic against
      systemic candidiasis without possessing direct candidacidal properties. Here we
      demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic
      cleavage of the constant region (Fc) of human IgG(1), is able to induce IL-6
      secretion and pIkB-alpha activation. More importantly, it causes an up-regulation
      of Dectin-1 expression. This leads to an increased activation of beta-glucan
      induced pSyk, CARD9 and pIkB-alpha, and an increase in the production of pro
      inflammatory cytokines such as IL-6, IL-12, IL-1beta and TNF-alpha. The increased
      activation of this pathway coincides with an augmented phagocytosis of non
      opsonized Candida albicans cells by monocytes. The findings suggest that some Fc
      peptides, potentially deriving from the proteolysis of immunoglobulins, may cause
      an unexpected immunoregulation in a way reminiscent of innate immunity molecules.

PMID- 22952832
TI  - High influenza a virus infection rates in Mallards bred for hunting in the
      Camargue, South of France.
AB  - During the last decade, the role of wildlife in emerging pathogen transmission to
      domestic animals has often been pointed out. Conversely, far less attention has
      been paid to pathogen transmission from domestic animals to wildlife. Here, we
      focus on the case of game restocking, which implies the release of millions of
      animals worldwide each year. We conducted a 2-year study in the Camargue
      (Southern France) to investigate the influence of hand-reared Mallard releases on
      avian influenza virus dynamics in surrounding wildlife. We sampled Mallards
      (cloacal swabs) from several game duck facilities in 2009 and 2010 before their
      release. A very high (99%) infection rate caused by an H10N7 strain was detected
      in the game bird facility we sampled in 2009. We did not detect this strain in
      shot ducks we sampled, neither during the 2008/2009 nor the 2009/2010 hunting
      seasons. In 2010 infection rates ranged from 0 to 24% in hand-reared ducks. The
      2009 H10N7 strain was fully sequenced. It results from multiple reassortment
      events between Eurasian low pathogenic strains. Interestingly, H10N7 strains had
      previously caused human infections in Egypt and Australia. The H10 and N7
      segments we sequenced were clearly distinct from the Australian ones but they
      belonged to the same large cluster as the Egyptian ones. We did not observe any
      mutation linked to increased virulence, transmission to mammals, or antiviral
      resistance in the H10N7 strain we identified. Our results indicate that the
      potential role of hand-reared Mallards in influenza virus epizootics must be
      taken into account given the likely risk of viral exchange between game bird
      facilities and wild habitats, owing to duck rearing conditions. Measures
      implemented to limit transmission from wildlife to domestic animals as well as
      measures to control transmission from domestic animals to wild ones need to be
      equally reinforced.

PMID- 22952833
TI  - Guillain-Barre syndrome-related Campylobacter jejuni in Bangladesh: ganglioside
      mimicry and cross-reactive antibodies.
AB  - BACKGROUND: Campylobacter jejuni is the predominant antecedent infection in
      Guillain-Barre syndrome (GBS). Molecular mimicry and cross-reactive immune
      responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of
      GBS, although this mechanism has not been established in patients from developing
      countries. We determined the carbohydrate mimicry between C. jejuni LOS and
      gangliosides, and the cross-reactive antibody response in patients with GBS in
      Bangladesh. METHODOLOGY: Sera from 97 GBS patients, and 120 neurological and
      family controls were tested for antibody reactivity against LOS from C. jejuni
      isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94)
      by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was
      determined by ELISA. The LOS outer core structures of C. jejuni strains
      associated with GBS/MFS were determined by mass spectrometry. PRINCIPLE FINDINGS:
      IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG
      antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients
      respectively, as compared to very low frequency (<3%) in controls (p<0.001).
      Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from
      the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the
      presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and
      BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be
      a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum
      reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50
      ug/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07
      developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1
      immune response. CONCLUSION: Carbohydrate mimicry between C. jejuni LOS and
      gangliosides, and cross-reactive serum antibody precipitate the majority of GBS
      cases in Bangladesh.

PMID- 22952834
TI  - Young children consider merit when sharing resources with others.
AB  - MERIT IS A KEY PRINCIPLE OF FAIRNESS: rewards should be distributed according to
      how much someone contributed to a task. Previous research suggests that children
      have an early ability to take merit into account in third-party situations but
      that merit-based sharing in first-party contexts does not emerge until school
      age. Here we provide evidence that three- and five-year-old children already use
      merit to share resources with others, even when sharing is costly for the child.
      In Study 1, a child and a puppet-partner collected coins that were later
      exchanged for rewards. We varied the work-contribution of both partners by
      manipulating how many coins each partner collected. Children kept fewer stickers
      in trials in which they had contributed less than in trials in which they had
      contributed more than the partner, showing that they took merit into account. Few
      children, however, gave away more than half of the stickers when the partner had
      worked more. Study 2 confirmed that children related their own work-contribution
      to their partner's, rather than simply focusing on their own contribution. Taken
      together, these studies show that merit-based sharing is apparent in young
      children; however it remains constrained by a self-serving bias.

PMID- 22952835
TI  - Temporo-spectral imaging of intrinsic optical signals during hypoxia-induced
      spreading depression-like depolarization.
AB  - Spreading depression (SD) is characterized by a sustained near-complete
      depolarization of neurons, a massive depolarization of glia, and a negative
      deflection of the extracellular DC potential. These electrophysiological signs
      are accompanied by an intrinsic optical signal (IOS) which arises from changes in
      light scattering and absorption. Even though the underlying mechanisms are
      unclear, the IOS serves as non-invasive tool to define the spatiotemporal
      dynamics of SD in brain slices. Usually the tissue is illuminated by white light,
      and light reflectance or transmittance is monitored. Using a polychromatic, fast
      switchable light source we now performed temporo-spectral recordings of the IOS
      associated with hypoxia-induced SD-like depolarization (HSD) in rat hippocampal
      slices kept in an interface recording chamber. Recording full illumination
      spectra (320-680 nm) yielded distinct reflectance profiles for the different
      phases of HSD. Early during hypoxia tissue reflectance decreased within almost
      the entire spectrum due to cell swelling. HSD was accompanied by a reversible
      reflectance increase being most pronounced at 400 nm and 460 nm. At 440 nm
      massive porphyrin absorption (Soret band) was detected. Hypotonic solutions,
      Ca(2+)-withdrawal and glial poisoning intensified the reflectance increase during
      HSD, whereas hypertonic solutions dampened it. Replacement of Cl(-) inverted the
      reflectance increase. Inducing HSD by cyanide distorted the IOS and reflectance
      at 340-400 nm increased irreversibly. The pronounced changes at short wavelengths
      (380 nm, 460 nm) and their cyanide sensitivity suggest that block of
      mitochondrial metabolism contributes to the IOS during HSD. For stable and
      reliable IOS recordings during HSD wavelengths of 460-560 nm are recommended.

PMID- 22952836
TI  - Toxicity of nano-zero valent iron to freshwater and marine organisms.
AB  - We tested whether three commercial forms (uncoated, organic coating, and iron
      oxide coating) of nano zero-valent iron (nZVI) are toxic to freshwater and marine
      organisms, specifically three species of marine phytoplankton, one species of
      freshwater phytoplankton, and a freshwater zooplankton species (Daphnia magna),
      because these organisms may be exposed downstream of where nZVI is applied to
      remediate polluted soil. The aggregation and reactivity of the three types of
      nZVI varied considerably, which was reflected in their toxicity. Since levels of
      Fe(2+) and Fe(3+) increase as the nZVI react, we also evaluated their toxicity
      independently. All four phytoplankton species displayed decreasing population
      growth rates, and Daphnia magna showed increasing mortality, in response to
      increasing levels of nZVI, and to a lesser degree with increasing Fe(2+) and
      Fe(3+). All forms of nZVI aggregated in soil and water, especially in the
      presence of a high concentration of calcium ions in groundwater, thus reducing
      their transports through the environment. However, uncoated nZVI aggregated
      extremely rapidly, thus vastly reducing the probability of environmental
      transport and potential for toxicity. This information can be used to design a
      risk management strategy to arrest the transport of injected nZVI beyond the
      intended remediation area, by injecting inert calcium salts as a barrier to
      transport.

PMID- 22952837
TI  - Macrophage migration inhibitory factor inhibits the migration of cartilage end
      plate-derived stem cells by reacting with CD74.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifunctional
      cytokine that regulates inflammatory reactions and the pathophysiology of many
      inflammatory diseases. Intervertebral disc (IVD) degeneration is characterized by
      an inflammatory reaction, but the potential role of MIF in IVD degeneration has
      not been determined. Recent studies have shown that MIF and its receptor, CD74,
      are involved in regulating the migration of human mesenchymal stem cells (MSCs);
      Thus, MIF might impair the ability of mesenchymal stem cells (MSCs) to home to
      injured tissues. Our previous studies indicated that cartilage endplate (CEP)
      derived stem cells (CESCs) as a type of MSCs exist in human degenerate IVDs.
      Here, we investigate the role of MIF in regulating the migration of CESCs.
      METHODS AND FINDINGS: CESCs were isolated and identified. We have shown that MIF
      was distributed in human degenerate IVD tissues and was subject to regulation by
      the pro-inflammatory cytokine TNF-alpha. Furthermore, in vitro cell migration
      assays revealed that nucleus pulposus (NP) cells inhibited the migration of CESCs
      in a number-dependent manner, and ELISA assays revealed that the amount of MIF in
      conditioned medium (CM) was significantly increased as a function of increasing
      cell number. Additionally, recombinant human MIF (r-MIF) inhibited the migration
      of CESCs in a dose-dependent manner. CESCs migration was restored when an
      antagonist of MIF, (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid
      methyl ester (ISO-1), was added. Finally, a CD74 activating antibody (CD74Ab) was
      used to examine the effect of CD74 on CESCs motility and inhibited the migration
      of CESCs in a dose-dependent manner. CONCLUSIONS: We have identified and
      characterized a novel regulatory mechanism governing cell migration during IVD
      degeneration. The results will benefit understanding of another possible
      mechanism for IVD degeneration, and might provide a new method to repair
      degenerate IVD by enhancing CESCs migration to degenerated NP tissues to exert
      their regenerative effects.

PMID- 22952838
TI  - Stapled BH3 peptides against MCL-1: mechanism and design using atomistic
      simulations.
AB  - Atomistic simulations of a set of stapled alpha helical peptides derived from the
      BH3 helix of MCL-1 (Stewart et al. (2010) Nat Chem Biol 6: 595-601) complexed to
      a fragment (residues 172-320) of MCL-1 revealed that the highest affinity is
      achieved when the staples engage the surface of MCL-1 as has also been
      demonstrated for p53-MDM2 (Joseph et al. (2010) Cell Cycle 9: 4560-4568; Baek et
      al. (2012) J Am Chem Soc 134: 103-106). Affinity is also modulated by the ability
      of the staples to pre-organize the peptides as helices. Molecular dynamics
      simulations of these stapled BH3 peptides were carried out followed by
      determination of the energies of interactions using MM/GBSA methods. These show
      that the location of the staple is a key determinant of a good binding stapled
      peptide from a bad binder. The good binder derives binding affinity from
      interactions between the hydrophobic staple and a hydrophobic patch on MCL-1. The
      position of the staple was varied, guiding the design of new stapled peptides
      with higher affinities.

PMID- 22952839
TI  - Swi1 associates with chromatin through the DDT domain and recruits Swi3 to
      preserve genomic integrity.
AB  - Swi1 and Swi3 form the replication fork protection complex and play critical
      roles in proper activation of the replication checkpoint and stabilization of
      replication forks in the fission yeast Schizosaccharomyces pombe. However, the
      mechanisms by which the Swi1-Swi3 complex regulates these processes are not well
      understood. Here, we report functional analyses of the Swi1-Swi3 complex in
      fission yeast. Swi1 possesses the DDT domain, a putative DNA binding domain found
      in a variety of chromatin remodeling factors. Consistently, the DDT domain
      containing region of Swi1 interacts with DNA in vitro, and mutations in the DDT
      domain eliminate the association of Swi1 with chromatin in S. pombe cells. DDT
      domain mutations also render cells highly sensitive to S-phase stressing agents
      and induce strong accumulation of Rad22-DNA repair foci, indicating that the DDT
      domain is involved in the activity of the Swi1-Swi3 complex. Interestingly, DDT
      domain mutations also abolish Swi1's ability to interact with Swi3 in cells.
      Furthermore, we show that Swi1 is required for efficient chromatin association of
      Swi3 and that the Swi1 C-terminal domain directly interacts with Swi3. These
      results indicate that Swi1 associates with chromatin through its DDT domain and
      recruits Swi3 to function together as the replication fork protection complex.

PMID- 22952840
TI  - Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against
      beta-amyloid toxicity in transgenic Caenorhabditis elegans.
AB  - Liuwei Dihuang (LWDH), a classic Chinese medicinal formula, has been used to
      improve or restore declined functions related to aging and geriatric diseases,
      such as impaired mobility, vision, hearing, cognition and memory. Here, we report
      on the effect and possible mechanisms of LWDH mediated protection of beta-amyloid
      (Abeta) induced paralysis in Caenorhabditis elegans using ethanol extract (LWDH
      EE) and water extract (LWDH-WE). Chemical profiling and quantitative analysis
      revealed the presence of different levels of bioactive components in these
      extracts. LWDH-WE was rich in polar components such as monosaccharide dimers and
      trimers, whereas LWDH-EE was enriched in terms of phenolic compounds such as
      gallic acid and paeonol. In vitro studies revealed higher DPPH radical scavenging
      activity for LWDH-EE as compared to that found for LWDH-WE. Neither LWDH-EE nor
      LWDH-WE were effective in inhibiting aggregation of Abeta in vitro. By contrast,
      LWDH-EE effectively delayed Abeta induced paralysis in the transgenic C. elegans
      (CL4176) model which expresses human Abeta1-42. Western blot revealed no
      treatment induced reduction in Abeta accumulation in CL4176 although a
      significant reduction was observed at an early stage with respect to beta-amyloid
      deposition in C. elegans strain CL2006 which constitutively expresses human
      Abeta1-42. In addition, LWDH-EE reduced in vivo reactive oxygen species (ROS) in
      C. elegans (CL4176) that correlated with increased survival of LWDH-EE treated N2
      worms under juglone-induced oxidative stress. Analysis with GFP reporter strain
      TJ375 revealed increased expression of hsp16.2::GFP after thermal stress whereas
      a minute induction was observed for sod3::GFP. Quantitative gene expression
      analysis revealed that LWDH-EE repressed the expression of amy1 in CL4176 while
      up-regulating hsp16.2 induced by elevating temperature. Taken together, these
      results suggest that LWDH extracts, particularly LWDH-EE, alleviated beta-amyloid
      induced toxicity, in part, through up-regulation of heat shock protein,
      antioxidant activity and reduced ROS in C. elegans.

PMID- 22952841
TI  - Exploring the natural variation for seedling traits and their link with seed
      dimensions in tomato.
AB  - The success of germination, growth and final yield of every crop depends to a
      large extent on the quality of the seeds used to grow the crop. Seed quality is
      defined as the viability and vigor attribute of a seed that enables the emergence
      and establishment of normal seedlings under a wide range of environments. We
      attempt to dissect the mechanisms involved in the acquisition of seed quality,
      through a combined approach of physiology and genetics. To achieve this goal we
      explored the genetic variation found in a RIL population of Solanum lycopersicum
      (cv. Moneymaker) x Solanum pimpinellifolium through extensive phenotyping of seed
      and seedling traits under both normal and nutrient stress conditions and root
      system architecture (RSA) traits under optimal conditions. We have identified 62
      major QTLs on 21 different positions for seed, seedling and RSA traits in this
      population. We identified QTLs that were common across both conditions, as well
      as specific to stress conditions. Most of the QTLs identified for seedling traits
      co-located with seed size and seed weight QTLs and the positive alleles were
      mostly contributed by the S. lycopersicum parent. Co-location of QTLs for
      different traits might suggest that the same locus has pleiotropic effects on
      multiple traits due to a common mechanistic basis. We show that seed weight has a
      strong effect on seedling vigor and these results are of great importance for the
      isolation of the corresponding genes and elucidation of the underlying
      mechanisms.

PMID- 22952842
TI  - Frequency matrix approach demonstrates high sequence quality in avian BARCODEs
      and highlights cryptic pseudogenes.
AB  - The accuracy of DNA barcode databases is critical for research and practical
      applications. Here we apply a frequency matrix to assess sequencing errors in a
      very large set of avian BARCODEs. Using 11,000 sequences from 2,700 bird species,
      we show most avian cytochrome c oxidase I (COI) nucleotide and amino acid
      sequences vary within a narrow range. Except for third codon positions, nearly
      all (96%) sites were highly conserved or limited to two nucleotides or two amino
      acids. A large number of positions had very low frequency variants present in
      single individuals of a species; these were strongly concentrated at the ends of
      the barcode segment, consistent with sequencing error. In addition, a small
      fraction (0.1%) of BARCODEs had multiple very low frequency variants shared among
      individuals of a species; these were found to represent overlooked cryptic
      pseudogenes lacking stop codons. The calculated upper limit of sequencing error
      was 8 * 10(-5) errors/nucleotide, which was relatively high for direct Sanger
      sequencing of amplified DNA, but unlikely to compromise species identification.
      Our results confirm the high quality of the avian BARCODE database and
      demonstrate significant quality improvement in avian COI records deposited in
      GenBank over the past decade. This approach has potential application for genetic
      database quality control, discovery of cryptic pseudogenes, and studies of low
      level genetic variation.

PMID- 22952843
TI  - Grey and white matter changes across the amyotrophic lateral sclerosis
      frontotemporal dementia continuum.
AB  - There is increasing evidence that amyotrophic lateral sclerosis (ALS) and
      frontotemporal dementia (FTD) lie on a clinical, pathological and genetic
      continuum with patients of one disease exhibiting features of the other.
      Nevertheless, to date, the underlying grey matter and white matter changes across
      the ALS-FTD disease continuum have not been explored. In this study fifty-three
      participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD
      (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical
      assessment plus structural imaging using voxel-based morphometry (VBM) and
      diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to
      examine grey and white matter differences and commonalities across the continuum.
      Importantly, patient groups were matched for age, education, gender and disease
      duration. VBM and DTI results showed that changes in the ALS group were confined
      mainly to the motor cortex and anterior cingulate as well as their underlying
      white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white
      matter changes involving frontal and temporal lobes. Extensive prefrontal cortex
      changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD
      could be distinguished from ALS by additional temporal lobe grey and white matter
      changes. Finally, ALS could be mainly distinguished from the other two groups by
      corticospinal tract degeneration. The present study shows for the first time that
      FTD and ALS overlap in anterior cingulate, motor cortex and related white matter
      tract changes across the whole continuum. Nevertheless, frontal and temporal
      atrophy as well as corticospinal tract degeneration emerged as marker for subtype
      classification, which will inform future diagnosis and target disease management
      across the continuum.

PMID- 22952844
TI  - Targeted ubiquitination and degradation of G-protein-coupled receptor kinase 5 by
      the DDB1-CUL4 ubiquitin ligase complex.
AB  - The G protein-coupled receptor kinases (GRKs) phosphorylate agonist occupied G
      protein-coupled receptors (GPCRs) and desensitize GPCR-mediated signaling. Recent
      studies indicate they also function non-catalytically via interaction with other
      proteins. In this study, a proteomic approach was used to screen interacting
      proteins of GRK5 in MDA-MB-231 cells and HUVEC cells. Mass spectrometry analysis
      reveals several proteins in the GRK5 immunocomplex including damaged DNA-binding
      protein 1 (DDB1), an adaptor subunit of the CUL4-ROC1 E3 ubiquitin ligase
      complex. Co-immunoprecipitation experiments confirmed the association of GRK5
      with DDB1-CUL4 complex, and reveal that DDB1 acts as an adapter to link GRK5 to
      CUL4 to form the complex. Overexpression of DDB1 promoted, whereas knockdown of
      DDB1 inhibited the ubiquitination of GRK5, and the degradation of GRK5 was
      reduced in cells deficient of DDB1. Furthermore, the depletion of DDB1 decreased
      Hsp90 inhibitor-induced GRK5 destabilization and UV irradiation-induced GRK5
      degradation. Thus, our study identified potential GRK5 interacting proteins, and
      reveals the association of GRK5 with DDB1 in cell and the regulation of GRK5
      level by DDB1-CUL4 ubiquitin ligase complex-dependent proteolysis pathway.

PMID- 22952845
TI  - Staphylococcus aureus methicillin-resistance factor fmtA is regulated by the
      global regulator SarA.
AB  - fmtA encodes a low-affinity penicillin binding protein in Staphylococcus aureus.
      It is part of the core cell wall stimulon and is involved in methicillin
      resistance in S. aureus. Here, we report that the transcription factor, SarA, a
      pleiotropic regulator of virulence genes in S. aureus, regulates the expression
      of fmtA. In vitro binding studies with purified SarA revealed that it binds to
      specific sites within the 541-bp promoter region of fmtA. Mutation of a key
      residue of the regulatory activity of SarA (Arg90) abolished binding of SarA to
      the fmtA promoter, suggesting that SarA binds specifically to the fmtA promoter
      region. In vivo analysis of the fmtA promoter using a lux operon reporter fusion
      show high level expression following oxacillin induction, which was abrogated in
      a sarA mutant strain. These data suggest that SarA is essential for the induction
      of fmtA expression by cell wall-specific antibiotics. Further, in vitro
      transcription studies show that SarA enhances fmtA transcription and suggest that
      regulation of fmtA could be via a SigA-dependent mechanism. Overall, our results
      show that SarA plays a direct role in the regulation of fmtA expression via
      binding to the fmtA promoter.

PMID- 22952846
TI  - Multi-scale molecular photoacoustic tomography of gene expression.
AB  - Photoacoustic tomography (PAT) is a molecular imaging technology. Unlike
      conventional reporter gene imaging, which is usually based on fluorescence,
      photoacoustic reporter gene imaging relies only on optical absorption. This work
      demonstrates several key merits of PAT using lacZ, one of the most widely used
      reporter genes in biology. We show that the expression of lacZ can be imaged by
      PAT as deep as 5.0 cm in biological tissue, with resolutions of ~1.0 mm and ~0.4
      mm in the lateral and axial directions, respectively. We further demonstrate non
      invasive, simultaneous imaging of a lacZ-expressing tumor and its surrounding
      microvasculature in vivo by dual-wavelength acoustic-resolution photoacoustic
      microscopy (AR-PAM), with a lateral resolution of 45 um and an axial resolution
      of 15 um. Finally, using optical-resolution photoacoustic microscopy (OR-PAM), we
      show intra-cellular localization of lacZ expression, with a lateral resolution of
      a fraction of a micron. These results suggest that PAT is a complementary tool to
      conventional optical fluorescence imaging of reporter genes for linking
      biological studies from the microscopic to the macroscopic scales.

PMID- 22952847
TI  - Consensus micro RNAs governing the switch of dormant tumors to the fast-growing
      angiogenic phenotype.
AB  - Tumor dormancy refers to a critical stage in cancer development in which tumor
      cells remain occult for a prolonged period of time until they eventually progress
      and become clinically apparent. We previously showed that the switch of dormant
      tumors to fast-growth is angiogenesis dependent and requires a stable
      transcriptional reprogramming in tumor cells. Considering microRNAs (miRs) as
      master regulators of transcriptome, we sought to investigate their role in the
      control of tumor dormancy. We report here the identification of a consensus set
      of 19 miRs that govern the phenotypic switch of human dormant breast carcinoma,
      glioblastoma, osteosarcoma, and liposarcoma tumors to fast-growth. Loss of
      expression of dormancy-associated miRs (DmiRs, 16/19) was the prevailing
      regulation pattern correlating with the switch of dormant tumors to fast-growth.
      The expression pattern of two DmiRs (miR-580 and 190) was confirmed to correlate
      with disease stage in human glioma specimens. Reconstitution of a single DmiR
      (miR-580, 588 or 190) led to phenotypic reversal of fast-growing angiogenic
      tumors towards prolonged tumor dormancy. Of note, 60% of angiogenic glioblastoma
      and 100% of angiogenic osteosarcoma over-expressing miR190 remained dormant
      during the entire observation period of ~ 120 days. Next, the ability of DmiRs to
      regulate angiogenesis and dormancy-associated genes was evaluated.
      Transcriptional reprogramming of tumors via DmiR-580, 588 or 190 over-expression
      resulted in downregulation of pro-angiogenic factors such as TIMP-3, bFGF and
      TGFalpha. In addition, a G-CSF independent downregulation of Bv8 was found as a
      common target of all three DmiRs and correlated with decreased tumor recruitment
      of bone marrow-derived CD11b+ Gr-1+ myeloid cells. In contrast, antiangiogenic
      and dormancy promoting pathways such as EphA5 and Angiomotin were upregulated in
      DmiR over-expressing tumors. This work suggests novel means to reverse the
      malignant tumor phenotype into an asymptomatic dormant state and may provide
      promising targets for early detection or prevention of cancer.

PMID- 22952848
TI  - Comparative metagenomics of toxic freshwater cyanobacteria bloom communities on
      two continents.
AB  - Toxic cyanobacterial blooms have persisted in freshwater systems around the world
      for centuries and appear to be globally increasing in frequency and severity.
      Toxins produced by bloom-associated cyanobacteria can have drastic impacts on the
      ecosystem and surrounding communities, and bloom biomass can disrupt aquatic food
      webs and act as a driver for hypoxia. Little is currently known regarding the
      genomic content of the Microcystis strains that form blooms or the companion
      heterotrophic community associated with bloom events. To address these issues, we
      examined the bloom-associated microbial communities in single samples from Lake
      Erie (North America), Lake Tai (Taihu, China), and Grand Lakes St. Marys (OH,
      USA) using comparative metagenomics. Together the Cyanobacteria and
      Proteobacteria comprised >90% of each bloom bacterial community sample, although
      the dominant phylum varied between systems. Relative to the existing Microcystis
      aeruginosa NIES 843 genome, sequences from Lake Erie and Taihu revealed a number
      of metagenomic islands that were absent in the environmental samples. Moreover,
      despite variation in the phylogenetic assignments of bloom-associated organisms,
      the functional potential of bloom members remained relatively constant between
      systems. This pattern was particularly noticeable in the genomic contribution of
      nitrogen assimilation genes. In Taihu, the genetic elements associated with the
      assimilation and metabolism of nitrogen were predominantly associated with
      Proteobacteria, while these functions in the North American lakes were primarily
      contributed to by the Cyanobacteria. Our observations build on an emerging body
      of metagenomic surveys describing the functional potential of microbial
      communities as more highly conserved than that of their phylogenetic makeup
      within natural systems.

PMID- 22952849
TI  - Decoding reveals plasticity in V3A as a result of motion perceptual learning.
AB  - Visual perceptual learning (VPL) is defined as visual performance improvement
      after visual experiences. VPL is often highly specific for a visual feature
      presented during training. Such specificity is observed in behavioral tuning
      function changes with the highest improvement centered on the trained feature and
      was originally thought to be evidence for changes in the early visual system
      associated with VPL. However, results of neurophysiological studies have been
      highly controversial concerning whether the plasticity underlying VPL occurs
      within the visual cortex. The controversy may be partially due to the lack of
      observation of neural tuning function changes in multiple visual areas in
      association with VPL. Here using human subjects we systematically compared
      behavioral tuning function changes after global motion detection training with
      decoded tuning function changes for 8 visual areas using pattern classification
      analysis on functional magnetic resonance imaging (fMRI) signals. We found that
      the behavioral tuning function changes were extremely highly correlated to
      decoded tuning function changes only in V3A, which is known to be highly
      responsive to global motion with human subjects. We conclude that VPL of a global
      motion detection task involves plasticity in a specific visual cortical area.

PMID- 22952850
TI  - Oxidative stress and modification of renal vascular permeability are associated
      with acute kidney injury during P. berghei ANKA infection.
AB  - Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality
      in adult patients hospitalized with severe form of the disease. However, the
      causes that lead to a framework of malaria-associated AKI are still poorly
      characterized. Some clinical studies speculate that oxidative stress products, a
      characteristic of Plasmodium infection, as well as proinflammatory response
      induced by the parasite are involved in its pathophysiology. Therefore, we aimed
      to investigate the development of malaria-associated AKI during infection by P.
      berghei ANKA, with special attention to the role played by the inflammatory
      response and the involvement of oxidative stress. For that, we took advantage of
      an experimental model of severe malaria that showed significant changes in the
      renal pathophysiology to investigate the role of malaria infection in the renal
      microvascular permeability and tissue injury. Therefore, BALB/c mice were
      infected with P. berghei ANKA. To assess renal function, creatinine, blood urea
      nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products
      of oxidative stress, as well as cytokine profile were quantified in plasma and
      renal tissue. The change of renal microvascular permeability, tissue hypoxia and
      cellular apoptosis were also evaluated. Parasite infection resulted in renal
      dysfunction. Furthermore, we observed increased expression of adhesion molecule,
      proinflammatory cytokines and products of oxidative stress, associated with a
      decrease mRNA expression of HO-1 in kidney tissue of infected mice. The
      measurement of lipoprotein oxidizability also showed a significant increase in
      plasma of infected animals. Together, our findings support the idea that products
      of oxidative stress, as well as the immune response against the parasite are
      crucial to changes in kidney architecture and microvascular endothelial
      permeability of BALB/c mice infected with P. berghei ANKA.

PMID- 22952851
TI  - Brassica napus PHR1 gene encoding a MYB-like protein functions in response to
      phosphate starvation.
AB  - Phosphorus (P) is one of the essential nutrient elements for plant development.
      In this work, BnPHR1 encoding a MYB transcription activator was isolated from
      Brassica napus. The characterization of nuclear localization and transcription
      activation ability suggest BnPHR1 is a transcriptional activator. The tissue
      expression and histochemical assay showed that BnPHR1 was predominantly expressed
      in roots and modulated by exogenous Pi in transcriptional level in roots under Pi
      deficiency conditions. Furthermore, overexpression of BnPHR1 in both Arabidopsis
      and B. napus remarkably enhanced the expression of the Pi-starvation-induced
      genes including ATPT2 and BnPT2 encoding the high-affinity Pi transporter.
      Additionally, BnPHR1 can in vivo bind the promoter sequence of ATPT2 and BnPT2 in
      both Arabidopsis and B. napus. Possibly, due to the activation of ATPT2 and
      BnPT2, or even more high-affinity Pi transporters, the excessive Pi was
      accumulated in transgenic plants, resulting in the crucially Pi toxicity to cells
      and subsequently retarding plant growth. Given the data together, BnPHR1, as
      crucial regulator, is regulated by exogenous Pi and directly activates those
      genes, which promote the uptake and homeostasis of Pi for plant growth.

PMID- 22952852
TI  - Chromatin structure of ribosomal RNA genes in dipterans and its relationship to
      the location of nucleolar organizers.
AB  - Nucleoli, nuclear organelles in which ribosomal RNA is synthesized and processed,
      emerge from nucleolar organizers (NORs) located in distinct chromosomal regions.
      In polytene nuclei of dipterans, nucleoli of some species can be observed under
      light microscopy exhibiting distinctive morphology: Drosophila and chironomid
      species display well-formed nucleoli in contrast to the fragmented and dispersed
      nucleoli seen in sciarid flies. The available data show no apparent relationship
      between nucleolar morphology and location of NORs in Diptera. The regulation of
      rRNA transcription involves controlling both the transcription rate per gene as
      well as the proportion of rRNA genes adopting a proper chromatin structure for
      transcription, since active and inactive rRNA gene copies coexist in NORs.
      Transcription units organized in nucleosomes and those lacking canonical
      nucleosomes can be analyzed by the method termed psoralen gel retarding assay
      (PGRA), allowing inferences on the ratio of active to inactive rRNA gene copies.
      In this work, possible connections between chromosomal location of NORs and
      proportion of active rRNA genes were studied in Drosophila melanogaster, and in
      chironomid and sciarid species. The data suggested a link between location of
      NORs and proportion of active rRNA genes since the copy number showing
      nucleosomal organization predominates when NORs are located in the pericentric
      heterochromatin. The results presented in this work are in agreement with
      previous data on the chromatin structure of rRNA genes from distantly related
      eukaryotes, as assessed by the PGRA.

PMID- 22952853
TI  - MED25 is a mediator component of HNF4alpha-driven transcription leading to
      insulin secretion in pancreatic beta-cells.
AB  - Unique nuclear receptor Hepatocyte Nuclear Factor 4alpha (HNF4alpha) is an
      essential transcriptional regulator for early development and proper function of
      pancreatic beta-cells, and its mutations are monogenic causes of a dominant
      inherited form of diabetes referred to as Maturity Onset Diabetes of the Young 1
      (MODY1). As a gene-specific transcription factor, HNF4alpha exerts its function
      through various molecular interactions, but its protein recruiting network has
      not been fully characterized. Here we report the identification of MED25 as one
      of the HNF4alpha binding partners in pancreatic beta-cells leading to insulin
      secretion which is impaired in MODY patients. MED25 is one of the subunits of the
      Mediator complex that is required for induction of RNA polymerase II
      transcription by various transcription factors including nuclear receptors. This
      HNF4alpha-MED25 interaction was initially identified by a yeast-two-hybrid
      method, confirmed by in vivo and in vitro analyses, and proven to be mediated
      through the MED25-LXXLL motif in a ligand-independent manner. Reporter-gene based
      transcription assays and siRNA/shRNA-based gene silencing approaches revealed
      that this interaction is crucial for full activation of HNF4alpha-mediated
      transcription, especially expression of target genes implicated in glucose
      stimulated insulin secretion. Selected MODY mutations at the LXXLL motif binding
      pocket disrupt these interactions and cause impaired insulin secretion through a
      'loss-of-function' mechanism.

PMID- 22952854
TI  - Inherited MST1 deficiency underlies susceptibility to EV-HPV infections.
AB  - Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous
      lesions caused by a specific group of related human papillomavirus genotypes (EV
      HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2
      deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has
      recently been described in two siblings with EV-HPV infections as well as other
      infectious and tumoral manifestations. We report here the whole-exome based
      discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency
      associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has
      recently been described in seven patients from three unrelated kindreds with
      profound T-cell deficiency and various viral and bacterial infections. The
      patient was also homozygous for a rare ERCC3 variation. Our findings broaden the
      clinical range of infections seen in MST1 deficiency and provide a new genetic
      etiology of susceptibility to EV-HPV infections. Together with the recent
      discovery of RHOH deficiency, they suggest that T cells are involved in the
      control of EV-HPVs, at least in some individuals.

PMID- 22952855
TI  - Abdominal contents from two large early cretaceous compsognathids (Dinosauria:
      Theropoda) demonstrate feeding on confuciusornithids and dromaeosaurids.
AB  - Two skeletons of the large compsognathid Sinocalliopteryx gigas include intact
      abdominal contents. Both specimens come from the Jianshangou Beds of the lower
      Yixian Formation (Neocomian), Liaoning, China. The holotype of S. gigas preserves
      a partial dromaeosaurid leg in the abdominal cavity, here attributed to
      Sinornithosaurus. A second, newly-discovered specimen preserves the remains of at
      least two individuals of the primitive avialan, Confuciusornis sanctus, in
      addition to acid-etched bones from a possible ornithischian. Although it cannot
      be stated whether such prey items were scavenged or actively hunted, the presence
      of two Confuciusornis in a grossly similar state of digestion suggests they were
      consumed in rapid succession. Given the lack of clear arboreal adaptations in
      Sinocalliopteryx, we suggest it may have been an adept stealth hunter.

PMID- 22952856
TI  - The taxonomic significance of species that have only been observed once: the
      genus Gymnodinium (Dinoflagellata) as an example.
AB  - Taxonomists have been tasked with cataloguing and quantifying the Earth's
      biodiversity. Their progress is measured in code-compliant species descriptions
      that include text, images, type material and molecular sequences. It is from this
      material that other researchers are to identify individuals of the same species
      in future observations. It has been estimated that 13% to 22% (depending on
      taxonomic group) of described species have only ever been observed once. Species
      that have only been observed at the time and place of their original description
      are referred to as oncers. Oncers are important to our current understanding of
      biodiversity. They may be validly described species that are members of a rare
      biosphere, or they may indicate endemism, or that these species are limited to
      very constrained niches. Alternatively, they may reflect that taxonomic practices
      are too poor to allow the organism to be re-identified or that the descriptions
      are unknown to other researchers. If the latter are true, our current tally of
      species will not be an accurate indication of what we know. In order to
      investigate this phenomenon and its potential causes, we examined the microbial
      eukaryote genus Gymnodinium. This genus contains 268 extant species, 103 (38%) of
      which have not been observed since their original description. We report traits
      of the original descriptions and interpret them in respect to the status of the
      species. We conclude that the majority of oncers were poorly described and their
      identity is ambiguous. As a result, we argue that the genus Gymnodinium contains
      only 234 identifiable species. Species that have been observed multiple times
      tend to have longer descriptions, written in English. The styles of individual
      authors have a major effect, with a few authors describing a disproportionate
      number of oncers. The information about the taxonomy of Gymnodinium that is
      available via the internet is incomplete, and reliance on it will not give access
      to all necessary knowledge. Six new names are presented - Gymnodinium campbelli
      for the homonymous name Gymnodinium translucens Campbell 1973, Gymnodinium
      antarcticum for the homonymous name Gymnodinium frigidum Balech 1965, Gymnodinium
      manchuriensis for the homonymous name Gymnodinium autumnale Skvortzov 1968,
      Gymnodinium christenum for the homonymous name Gymnodinium irregulare Christen
      1959, Gymnodinium conkufferi for the homonymous name Gymnodinium irregulare
      Conrad & Kufferath 1954 and Gymnodinium chinensis for the homonymous name
      Gymnodinium frigidum Skvortzov 1968.

PMID- 22952858
TI  - High resolution imaging of vascular function in zebrafish.
AB  - RATIONALE: The role of the endothelium in the pathogenesis of cardiovascular
      disease is an emerging field of study, necessitating the development of
      appropriate model systems and methodologies to investigate the multifaceted
      nature of endothelial dysfunction including disturbed barrier function and
      impaired vascular reactivity. OBJECTIVE: We aimed to develop and test an
      optimized high-speed imaging platform to obtain quantitative real-time measures
      of blood flow, vessel diameter and endothelial barrier function in order to
      assess vascular function in live vertebrate models. METHODS AND RESULTS: We used
      a combination of cutting-edge optical imaging techniques, including high-speed,
      camera-based imaging (up to 1000 frames/second), and 3D confocal methods to
      collect real time metrics of vascular performance and assess the dynamic response
      to the thromboxane A(2) (TXA(2)) analogue, U-46619 (1 uM), in transgenic
      zebrafish larvae. Data obtained in 3 and 5 day post-fertilization larvae show
      that these methods are capable of imaging blood flow in a large (1 mm) segment of
      the vessel of interest over many cardiac cycles, with sufficient speed and
      sensitivity such that the trajectories of individual erythrocytes can be resolved
      in real time. Further, we are able to map changes in the three dimensional sizes
      of vessels and assess barrier function by visualizing the continuity of the
      endothelial layer combined with measurements of extravasation of fluorescent
      microspheres. CONCLUSIONS: We propose that this system-based microscopic approach
      can be used to combine measures of physiologic function with molecular behavior
      in zebrafish models of human vascular disease.

PMID- 22952857
TI  - Allele-biased expression in differentiating human neurons: implications for
      neuropsychiatric disorders.
AB  - Stochastic processes and imprinting, along with genetic factors, lead to
      monoallelic or allele-biased gene expression. Stochastic monoallelic expression
      fine-tunes information processing in immune cells and the olfactory system, and
      imprinting plays an important role in development. Recent studies suggest that
      both stochastic events and imprinting may be more widespread than previously
      considered. We are interested in allele-biased gene expression occurring in the
      brain because parent-of-origin effects suggestive of imprinting appear to play a
      role in the transmission of schizophrenia (SZ) and autism spectrum disorders
      (ASD) in some families. In addition, allele-biased expression could help explain
      monozygotic (MZ) twin discordance and reduced penetrance. The ability to study
      allele-biased expression in human neurons has been transformed with the advent of
      induced pluripotent stem cell (iPSC) technology and next generation sequencing.
      Using transcriptome sequencing (RNA-Seq) we identified 801 genes in
      differentiating neurons that were expressed in an allele-biased manner. These
      included a number of putative SZ and ASD candidates, such as A2BP1 (RBFOX1),
      ERBB4, NLGN4X, NRG1, NRG3, NRXN1, and NLGN1. Overall, there was a modest
      enrichment for SZ and ASD candidate genes among those that showed evidence for
      allele-biased expression (chi-square, p = 0.02). In addition to helping explain
      MZ twin discordance and reduced penetrance, the capacity to group many candidate
      genes affecting a variety of molecular and cellular pathways under a common
      regulatory process - allele-biased expression - could have therapeutic
      implications.

PMID- 22952859
TI  - Mapping functional traits: comparing abundance and presence-absence estimates at
      large spatial scales.
AB  - Efforts to quantify the composition of biological communities increasingly focus
      on functional traits. The composition of communities in terms of traits can be
      summarized in several ways. Ecologists are beginning to map the geographic
      distribution of trait-based metrics from various sources of data, but the maps
      have not been tested against independent data. Using data for birds of the
      Western Hemisphere, we test for the first time the most commonly used method for
      mapping community trait composition - overlaying range maps, which assumes that
      the local abundance of a given species is unrelated to the traits in question -
      and three new methods that as well as the range maps include varying degrees of
      information about interspecific and geographic variation in abundance. For each
      method, and for four traits (body mass, generation length, migratory behaviour,
      diet) we calculated community-weighted mean of trait values, functional richness
      and functional divergence. The maps based on species ranges and limited abundance
      data were compared with independent data on community species composition from
      the American Christmas Bird Count (CBC) scheme coupled with data on traits. The
      correspondence with observed community composition at the CBC sites was mostly
      positive (62/73 correlations) but varied widely depending on the metric of
      community composition and method used (R(2): 5.6 * 10(-7) to 0.82, with a median
      of 0.12). Importantly, the commonly-used range-overlap method resulted in the
      best fit (21/22 correlations positive; R(2): 0.004 to 0.8, with a median of
      0.33). Given the paucity of data on the local abundance of species, overlaying
      range maps appears to be the best available method for estimating patterns of
      community composition, but the poor fit for some metrics suggests that local
      abundance data are urgently needed to allow more accurate estimates of the
      composition of communities.

PMID- 22952860
TI  - Cross-complementation study of the flagellar type III export apparatus membrane
      protein FlhB.
AB  - The bacterial type III export apparatus is found in the flagellum and in the
      needle complex of some pathogenic Gram-negative bacteria. In the needle complex
      its function is to secrete effector proteins for infection into Eukaryotic cells.
      In the bacterial flagellum it exports specific proteins for the building of the
      flagellum during its assembly. The export apparatus is composed of about five
      membrane proteins and three soluble proteins. The mechanism of the export
      apparatus is not fully understood. The five membrane proteins are well conserved
      and essential. Here a cross-complementation assay was performed: substituting in
      the flagellar system of Salmonella one of these membrane proteins, FlhB, by the
      FlhB ortholog from Aquifex aeolicus (an evolutionary distant hyperthermophilic
      bacteria) or a chimeric protein (AquSalFlhB) made by the combination of the trans
      membrane domain of A. aeolicus FlhB with the cytoplasmic domain of Salmonella
      FlhB dramatically reduced numbers of flagella and motility. From cells expressing
      the chimeric AquSalFlhB protein, suppressor mutants with enhanced motility were
      isolated and the mutations were identified using whole genome sequencing. Gain-of
      function mutations were found in the gene encoding FlhA, another membrane protein
      of the type III export apparatus. Also, mutations were identified in genes
      encoding 4-hydroxybenzoate octaprenyltransferase, ubiquinone/menaquinone
      biosynthesis methyltransferase, and 4-hydroxy-3-methylbut-2-en-1-yl diphosphate
      synthase, which are required for ubiquinone biosynthesis. The mutations were
      shown by reversed-phase high performance liquid chromatography to reduce the
      quinone pool of the cytoplasmic membrane. Ubiquinone biosynthesis could be
      restored for the strain bearing a mutated gene for 4-hydroxybenzoate
      octaprenyltransferase by the addition of excess exogenous 4-hydroxybenzoate.
      Restoring the level of ubiquinone reduced flagella biogenesis with the AquSalFlhB
      chimera demonstrating that the respiratory chain quinone pool is responsible for
      this phenomenon.

PMID- 22952861
TI  - Deep insight into the Ganoderma lucidum by comprehensive analysis of its
      transcriptome.
AB  - BACKGROUND: Ganoderma lucidum is a basidiomycete white rot fungus and is of
      medicinal importance in China, Japan and other countries in the Asiatic region.
      To date, much research has been performed in identifying the medicinal
      ingredients in Ganoderma lucidum. Despite its important therapeutic effects in
      disease, little is known about Ganoderma lucidum at the genomic level. In order
      to gain a molecular understanding of this fungus, we utilized Illumina high
      throughput technology to sequence and analyze the transcriptome of Ganoderma
      lucidum. METHODOLOGY/PRINCIPAL FINDINGS: We obtained 6,439,690 and 6,416,670 high
      quality reads from the mycelium and fruiting body of Ganoderma lucidum, and these
      were assembled to form 18,892 and 27,408 unigenes, respectively. A similarity
      search was performed against the NCBI non-redundant nucleotide database and a
      customized database composed of five fungal genomes. 11,098 and 8, 775 unigenes
      were matched to the NCBI non-redundant nucleotide database and our customized
      database, respectively. All unigenes were subjected to annotation by Gene
      Ontology, Eukaryotic Orthologous Group terms and Kyoto Encyclopedia of Genes and
      Genomes. Differentially expressed genes from the Ganoderma lucidum mycelium and
      fruiting body stage were analyzed, resulting in the identification of 13 unigenes
      which are involved in the terpenoid backbone biosynthesis pathway. Quantitative
      real-time PCR was used to confirm the expression levels of these unigenes.
      Ganoderma lucidum was also studied for wood degrading activity and a total of 22
      putative FOLymes (fungal oxidative lignin enzymes) and 120 CAZymes (carbohydrate
      active enzymes) were predicted from our Ganoderma lucidum transcriptome.
      CONCLUSIONS: Our study provides comprehensive gene expression information on
      Ganoderma lucidum at the transcriptional level, which will form the foundation
      for functional genomics studies in this fungus. The use of Illumina sequencing
      technology has made de novo transcriptome assembly and gene expression analysis
      possible in species that lack full genome information.

PMID- 22952862
TI  - A novel immunodiagnostic assay to detect serum antibody response against selected
      soluble egg antigen fractions from Schistosoma japonicum.
AB  - BACKGROUND: Schistosomiasis japonica remains a real threat to public health in
      China. The currently used immunodiagnostic assays are sensitive and have a
      certain degree of specificity, however, they all use complex crude antigens, are
      based on detection of schistosome-specific antibodies, and have been shown to
      cross-react with other parasitic diseases. Therefore, these assays cannot be used
      to evaluate chemotherapy efficacy. The development of highly sensitive and highly
      specific immunodiagnostic techniques that can monitor the decline of antibodies
      specific for S. japonica will be extremely valuable as part of the ongoing
      strategy to control schistosomiasis in endemic areas. Here we report on the
      identification of unique fraction antigens of soluble egg antigen (SEA) to which
      the antibodies disappear 7 weeks after effective treatment. Furthermore, we use
      these SEA fractions to develop a modified assay with both high sensitivity and
      specificity. METHODOLOGY/PRINCIPAL FINDINGS: SEA of S. japonicum was fractionated
      by electrophoresis using 7.5% SDS-PAGE under non-reducing conditions. The SEA
      fraction antigens to which antibodies were decreased soon after treatment were
      collected and used as the detection antigens to establish the FA-ELISA. Sera from
      patients with acute and chronic schistosomiasis infection, healthy people, and
      those with other parasitic diseases, were used to evaluate their sensitivity and
      specificity. Furthermore, sera from patients with chronic schistosomiasis
      infection were evaluated before and after treatment at different time points to
      evaluate their chemotherapeutic efficacy. CONCLUSION/SIGNIFICANCE: We
      demonstrated that this novel FA-ELISA provided high sensitivity and specificity,
      with very low cross-reactivity, and can serve as an effective tool to determine
      the efficacy of chemotherapy against S. japonicum.

PMID- 22952863
TI  - Protein arginine methyltransferase 5 functions in opposite ways in the cytoplasm
      and nucleus of prostate cancer cells.
AB  - Protein arginine methyltransferase 5 (PRMT5) plays multiple roles in a large
      number of cellular processes, and its subcellular localization is dynamically
      regulated during mouse development and cellular differentiation. However, little
      is known of the functional differences between PRMT5 in the cytoplasm and PRMT5
      in the nucleus. Here, we demonstrated that PRMT5 predominantly localized in the
      cytoplasm of prostate cancer cells. Subcellular localization assays designed to
      span the entire open-reading frame of the PRMT5 protein revealed the presence of
      three nuclear exclusion signals (NESs) in the PRMT5 protein. PRMT5 and
      p44/MED50/WD45/WDR77 co-localize in the cytoplasm, and both are required for the
      growth of prostate cancer cells in an PRMT5 methyltransferase activity-dependent
      manner. In contrast, PRMT5 in the nucleus inhibited cell growth in a
      methyltransferase activity-independent manner. Consistent with these
      observations, PRMT5 localized in the nucleus in benign prostate epithelium,
      whereas it localized in the cytoplasm in prostate premalignant and cancer
      tissues. We further found that PRMT5 alone methylated both histone H4 and SmD3
      proteins but PRMT5 complexed with p44 and pICln methylated SmD3 but not histone
      H4. These results imply a novel mechanism by which PRMT5 controls cell growth and
      contributes to prostate tumorigenesis.

PMID- 22952864
TI  - Unusual long-chain N-acyl homoserine lactone production by and presence of quorum
      quenching activity in bacterial isolates from diseased tilapia fish.
AB  - Growth-dependent cell-cell communication termed quorum sensing is a key
      regulatory system in bacteria for controlling gene expression including virulence
      factors. In this study five potential bacterial pathogens including Bacillus sp.
      W2.2, Klebsiella sp. W4.2, Pseudomonas sp. W3 and W3.1 and Serratia sp. W2.3 were
      isolated from diseased Tilapia fish in Malaysia, supplied by the leading global
      fish supplier. Proteolytic activity assays confirmed that with the exception of
      Klebsiella sp. W4.2, all isolates showed distinct proteolytic activity.
      Furthermore Bacillus sp. W2.2 and Pseudomonas sp. strains W3 and W3.1 also
      displayed haemolytic activity. By using high resolution liquid chromatography
      mass spectrometry, we revealed the presence of unusually long-chain N-(3
      oxohexadecanoyl)-homoserine lactone (3-oxo-C16-HSL) from Pseudomonas sp. W3.1 and
      N-dodecanoyl-homoserine lactone (C12-HSL) from Serratia sp. W2.3, respectively.
      Interestingly, Pseudomonas sp. W3.1 also produced a wide range of Pseudomonas
      quinolone signalling (PQS) molecules. Pseudomonas sp. W3 did not show any quorum
      sensing properties but possessed quorum quenching activity that inactivated AHLs.
      This study is the first documentation that shows unusual long-chain AHLs
      production in Serratia sp. and Pseudomonas sp. isolated from diseased fish and
      the latter also produce a wide range of PQS molecules.

PMID- 22952865
TI  - Development and degeneration of cone bipolar cells are independent of cone
      photoreceptors in a mouse model of retinitis pigmentosa.
AB  - Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal
      degeneration. Whether cone bipolar cells establish regular retinal mosaics and
      mature morphologies, and resist degeneration are not completely understood. To
      explore these issues, we backcrossed a transgenic mouse expressing enhanced green
      fluorescent protein (EGFP) in one subset of cone bipolar cells (type 7) into rd1
      mice, a classic mouse model of retinal degeneration, to examine the development
      and survival of cone bipolar cells in a background of retinal degeneration. Our
      data revealed that both the development and degeneration of cone bipolar cells
      are independent of the normal activity of cone photoreceptors. We found that type
      7 cone bipolar cells achieved a uniform tiling of the retinal surface and
      developed normal dendritic and axonal arbors without the influence of cone
      photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar
      cells, contrary to our belief of central-to-peripheral progression, was spatially
      uniform across the retina independent of the spatiotemporal pattern of cone
      degeneration. The results have important implications for the design of more
      effective therapies to restore vision in retinal degeneration.

PMID- 22952866
TI  - Cortactin as a target for FAK in the regulation of focal adhesion dynamics.
AB  - BACKGROUND: Efficient cell movement requires the dynamic regulation of focal
      adhesion (FA) formation and turnover. FAs are integrin-associated sites of cell
      attachment and establish linkages to the cellular actin cytoskeleton. Cells
      without focal adhesion kinase (FAK), an integrin-activated tyrosine kinase,
      exhibit defects in FA turnover and cell motility. Cortactin is an actin binding
      adaptor protein that can influence FA dynamics. FAK and cortactin interact, but
      the cellular role of this complex remains unclear. PRINCIPAL FINDINGS: Using FAK
      null fibroblasts stably reconstituted with green fluorescent protein (GFP) tagged
      FAK constructs, we find that FAK activity and FAK C-terminal proline-rich region
      2 (PRR2) and PRR3 are required for FA turnover and cell motility. Cortactin binds
      directly to FAK PRR2 and PRR3 sites via its SH3 domain and cortactin expression
      is important in promoting FA turnover and GFP-FAK release from FAs. FAK-cortactin
      binding is negatively-regulated by FAK activity and associated with cortactin
      tyrosine phosphorylation. FAK directly phosphorylates cortactin at Y421 and Y466
      and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine
      (3YF) prevented FAK-enhanced FA turnover and cell motility. However, phospho
      mimetic cortactin mutated to glutamic acid (3YE) did not affect FA dynamics and
      did not rescue FA turnover defects in cells with inhibited FAK activity or with
      PRR2-mutated FAK that does not bind cortactin. CONCLUSIONS: Our results support a
      model whereby FAK-mediated FA remodeling may occur through the formation of a FAK
      cortactin signaling complex. This involves a cycle of cortactin binding to FAK,
      cortactin tyrosine phosphorylation, and subsequent cortactin-FAK dissociation
      accompanied by FA turnover and cell movement.

PMID- 22952867
TI  - Induction of histiocytic sarcoma in mouse skeletal muscle.
AB  - Myeloid sarcomas are extramedullary accumulations of immature myeloid cells that
      may present with or without evidence of pathologic involvement of the bone marrow
      or peripheral blood, and often coincide with or precede a diagnosis of acute
      myeloid leukemia (AML). A dearth of experimental models has hampered the study of
      myeloid sarcomas and led us to establish a new system in which tumor induction
      can be evaluated in an easily accessible non-hematopoietic tissue compartment.
      Using ex-vivo transduction of oncogenic Kras(G12V) into p16/p19(-/-) bone marrow
      cells, we generated transplantable leukemia-initiating cells that rapidly induced
      tumor formation in the skeletal muscle of immunocompromised NOD.SCID mice. In
      this model, murine histiocytic sarcomas, equivalent to human myeloid sarcomas,
      emerged at the injection site 30-50 days after cell implantation and consisted of
      tightly packed monotypic cells that were CD48+, CD47+ and Mac1+, with low or
      absent expression of other hematopoietic lineage markers. Tumor cells also
      infiltrated the bone marrow, spleen and other non-hematopoietic organs of tumor
      bearing animals, leading to systemic illness (leukemia) within two weeks of tumor
      detection. P16/p19(-/-); Kras(G12V) myeloid sarcomas were multi-clonal, with
      dominant clones selected during secondary transplantation. The systemic leukemic
      phenotypes exhibited by histiocytic sarcoma-bearing mice were nearly identical to
      those of animals in which leukemia was introduced by intravenous transplantation
      of the same donor cells. Moreover, murine histiocytic sarcoma could be similarly
      induced by intramuscular injection of MLL-AF9 leukemia cells. This study
      establishes a novel, transplantable model of murine histiocytic/myeloid sarcoma
      that recapitulates the natural progression of these malignancies to systemic
      disease and indicates a cell autonomous leukemogenic mechanism.

PMID- 22952868
TI  - Tolerance induction by exosomes from immature dendritic cells and rapamycin in a
      mouse cardiac allograft model.
AB  - BACKGROUND: Dendritic cells (DCs) release bioactive exosomes that play an
      important role in immune regulation. Because they express low levels of class I
      major histocompatibility complex (MHC) and co-stimulatory molecules, exosomes
      derived from donor immature DCs (imDex) prolong allograft survival by inhibiting
      T-cell activation. However, this effect is limited and does not induce
      immunological tolerance when imDex are administered alone. Thus, we tested the
      effect of combined treatment with donor imDex and low-dose rapamycin on inducing
      tolerance in a mouse cardiac transplantation model. METHODS: ImDex were obtained
      from the culture supernatant of immature DCs derived from donor mouse (C57BL/6)
      bone marrow and were injected with suboptimal doses of rapamycin into recipient
      mouse (BALB/c) before and after transplantation. The capacity of this treatment
      to induce immune tolerance was analyzed in vitro and in vivo using the mouse
      cardiac transplantation model. RESULTS: Donor imDex expressed moderate levels of
      MHC class II and low levels of MHC class I and co-stimulatory molecules, but
      neither imDex nor subtherapeutic rapamycin dose alone induced cardiac allograft
      tolerance. Combined treatment with imDex and rapamycin, however, led to donor
      specific cardiac allograft tolerance. This effect was accompanied by decreased
      anti-donor antigen cellular response and an increased percentage of spleen
      CD4(+)CD25(+) T cells in recipients. Furthermore, this donor specific tolerance
      could be further transferred to naive allograft recipients through injection of
      splenocytes, but not serum, from tolerant recipients. CONCLUSION: Combined with
      immunosuppressive treatment, donor imDex can prolong cardiac allograft survival
      and induce donor specific allograft tolerance.

PMID- 22952869
TI  - Host genetic background impacts disease outcome during intrauterine infection
      with Ureaplasma parvum.
AB  - Ureaplasma parvum, an opportunistic pathogen of the human urogenital tract, has
      been implicated in contributing to chorioamnionitis, fetal morbidity, and fetal
      mortality. It has been proposed that the host genetic background is a critical
      factor in adverse pregnancy outcome as sequela to U. parvum intra-amniotic
      infection. To test this hypothesis we assessed the impact of intrauterine U.
      parvum infection in the prototypical TH1/M1 C57BL/6 and TH2/M2 BALB/c mouse
      strain. Sterile medium or U. parvum was inoculated into each uterine horn and
      animals were evaluated for intra-amniotic infection, fetal infection,
      chorioamnionitis and fetal pathology at 72 hours post-inoculation. Disease
      outcome was assessed by microbial culture, in situ detection of U. parvum in
      fetal and utero-placental tissues, grading of chorioamnionitis, and placental
      gene expression of IL-1alpha, IL-1beta, IL-6, TNF-alpha, S100A8, and S100A9.
      Placental infection and colonization rates were equivalent in both strains. The
      in situ distribution of U. parvum in placental tissues was also similar. However,
      a significantly greater proportion of BALB/c fetuses were infected (P<0.02).
      C57BL/6 infected animals predominantly exhibited mild to moderate
      chorioamnionitis (P<0.0001), and a significant reduction in placental expression
      of IL-1alpha, IL-1beta, IL-6, TNF-alpha, S100A8, and S100A9 compared to sham
      controls (P<0.02). Conversely, severe protracted chorioamnionitis with cellular
      necrosis was the predominant lesion phenotype in BALB/c mice, which also
      exhibited a significant increase in placental expression of IL-1alpha, IL-1beta,
      IL-6, TNF-alpha, S100A8, and S100A9 (P<0.01). Fetal pathology in BALB/c was multi
      organ and included brain, lung, heart, liver, and intestine, whereas fetal
      pathology in C57BL/6 was only detected in the liver and intestines. These results
      confirm that the host genetic background is a major determinant in ureaplasmal
      induced chorioamnionitis with fetal infection and fetal inflammatory response.

PMID- 22952871
TI  - Plasmacytoid dendritic cells are inefficient in activation of human regulatory T
      cells.
AB  - BACKGROUND: Dendritic cells (DC) play a key role in initiation and regulation of
      immune responses. Plasmacytoid DC (pDC), a small subset of DC, characterized as
      type-I interferon producing cells, are critically involved in anti-viral immune
      responses, but also mediate tolerance by induction of regulatory T cells (Treg).
      In this study, we compared the capacity of human pDC and conventional DC (cDC) to
      modulate T cell activity in presence of Foxp3(+) Treg. PRINCIPAL FINDINGS: In
      coculture of T effector cells (Teff) and Treg, activated cDC overcome Treg
      anergy, abrogate their suppressive function and induce Teff proliferation. In
      contrast, pDC do not break Treg anergy but induce Teff proliferation even in
      coculture with Treg. Lack of Treg-mediated suppression is independent of
      proinflammatory cytokines like IFN-alpha, IL-1, IL-6 and TNF-alpha. Phenotyping
      of pDC-stimulated Treg reveals a reduced expression of Treg activation markers
      GARP and CTLA-4. Additional stimulation by anti-CD3 antibodies enhances surface
      expression of GARP and CTLA-4 on Treg and consequently reconstitutes their
      suppressive function, while increased costimulation with anti-CD28 antibodies is
      ineffective. CONCLUSIONS/SIGNIFICANCE: Our data show that activated pDC induce
      Teff proliferation, but are insufficient for functional Treg activation and,
      therefore, allow expansion of Teff also in presence of Treg.

PMID- 22952870
TI  - Meal time shift disturbs circadian rhythmicity along with metabolic and
      behavioral alterations in mice.
AB  - In modern society, growing numbers of people are engaged in various forms of
      shift works or trans-meridian travels. Such circadian misalignment is known to
      disturb endogenous diurnal rhythms, which may lead to harmful physiological
      consequences including metabolic syndrome, obesity, cancer, cardiovascular
      disorders, and gastric disorders as well as other physical and mental disorders.
      However, the precise mechanism(s) underlying these changes are yet unclear. The
      present work, therefore examined the effects of 6 h advance or delay of usual
      meal time on diurnal rhythmicities in home cage activity (HCA), body temperature
      (BT), blood metabolic markers, glucose homeostasis, and expression of genes that
      are involved in cholesterol homeostasis by feeding young adult male mice in a
      time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a
      significant portion (42%) of subjects, while 6 h advance caused a torpor-like
      symptom during the late scotophase. Accordingly, daily rhythms of blood glucose
      and triglyceride were differentially affected by time-restrictive feeding regimen
      with concurrent metabolic alterations. Along with these physiological changes,
      time-restrictive feeding also influenced the circadian expression patterns of low
      density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors.
      Strikingly, chronic advance of meal time induced insulin resistance, while
      chronic delay significantly elevated blood glucose levels. Taken together, our
      findings indicate that persistent shifts in usual meal time impact the diurnal
      rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby
      posing critical implications for the health and diseases of shift workers.

PMID- 22952872
TI  - Evolving strategies, opportunistic implementation: HIV risk reduction in Tanzania
      in the context of an incentive-based HIV prevention intervention.
AB  - BACKGROUND: Behavior change communication (BCC) interventions, while still a
      necessary component of HIV prevention, have not on their own been shown to be
      sufficient to stem the tide of the epidemic. The shortcomings of BCC
      interventions are partly due to barriers arising from structural or economic
      constraints. Arguments are being made for combination prevention packages that
      include behavior change, biomedical, and structural interventions to address the
      complex set of risk factors that may lead to HIV infection. METHODS: In 2009/2010
      we conducted 216 in-depth interviews with a subset of study participants enrolled
      in the RESPECT study - an HIV prevention trial in Tanzania that used cash awards
      to incentivize safer sexual behaviors. We analyzed community diaries to
      understand how the study was perceived in the community. We drew on these data to
      enhance our understanding of how the intervention influenced strategies for risk
      reduction. RESULTS: We found that certain situations provide increased leverage
      for sexual negotiation, and these situations facilitated opportunistic
      implementation of risk reduction strategies. Opportunities enabled by the RESPECT
      intervention included leveraging conditional cash awards, but participants also
      emphasized the importance of exploiting new health status knowledge from regular
      STI testing. Risk reduction strategies included condom use within partnerships
      and/or with other partners, and an unexpected emphasis on temporary abstinence.
      CONCLUSIONS: Our results highlight the importance of increasing opportunities for
      implementing risk reduction strategies. We found that an incentive-based
      intervention could be effective in part by creating such opportunities,
      particularly among groups such as women with limited sexual agency. The results
      provide new evidence that expanding regular testing of STIs is another important
      mechanism for providing opportunities for negotiating behavior change, beyond the
      direct benefits of testing. Exploiting the latent demand for STI testing should
      receive renewed attention as part of innovative new combination interventions for
      HIV prevention.

PMID- 22952873
TI  - Gene network and pathway analysis of mice with conditional ablation of Dicer in
      post-mitotic neurons.
AB  - BACKGROUND: The small non-protein-coding microRNAs (miRNAs) have emerged as
      critical regulators of neuronal differentiation, identity and survival. To date,
      however, little is known about the genes and molecular networks regulated by
      neuronal miRNAs in vivo, particularly in the adult mammalian brain.
      METHODOLOGY/PRINCIPAL FINDINGS: We analyzed whole genome microarrays from mice
      lacking Dicer, the enzyme responsible for miRNA production, specifically in
      postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly
      (P<0.05, FDR<0.25) misregulated in the conditional Dicer knockout mice. Ten
      genes, including Tnrc6c, Dnmt3a, and Limk1, were validated by real time
      quantitative RT-PCR. Upregulated transcripts were enriched in nonneuronal genes,
      which is consistent with previous studies in vitro. Microarray data mining showed
      that upregulated genes were enriched in biological processes related to gene
      expression regulation, while downregulated genes were associated with neuronal
      functions. Molecular pathways associated with neurological disorders, cellular
      organization and cellular maintenance were altered in the Dicer mutant mice.
      Numerous miRNA target sites were enriched in the 3'untranslated region (3'UTR) of
      upregulated genes, the most significant corresponding to the miR-124 seed
      sequence. Interestingly, our results suggest that, in addition to miR-124, a
      large fraction of the neuronal miRNome participates, by order of abundance, in
      coordinated gene expression regulation and neuronal maintenance.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these results provide new clues into
      the role of specific miRNA pathways in the regulation of brain identity and
      maintenance in adult mice.

PMID- 22952874
TI  - Allele loss and down-regulation of heparanase gene are associated with the
      progression and poor prognosis of hepatocellular carcinoma.
AB  - OBJECTIVES: The role of heparanase (HPSE) gene in cancers including
      hepatocellular carcinoma (HCC) is currently controversial. This study was aimed
      at investigating the impact of genetic alteration and expression change of HPSE
      on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in
      three different aspects: (1) loss of heterozygosity (LOH) by a custom SNP
      microarray and DNA copy number by real-time PCR; (2) mRNA level by qRT-PCR; and
      (3) protein expression by immunohistochemistry. The clinical significances of
      allele loss and expression change of HPSE were analyzed. RESULTS: Microarray
      analysis showed that the average LOH frequency for 10 SNPs located within HPSE
      gene was 31.6%, three of which were significantly correlated with tumor grade,
      serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA
      copy number loss of HPSE was observed in 38.74% (43/111) of HCC cases. HPSE mRNA
      level was notably reduced in 74.1% (83/112) of tumor tissues compared with non
      tumor liver tissues, which was significantly associated with DNA copy number
      loss, increased tumor size, and post-operative metastasis. HPSE protein level was
      also remarkably reduced in 66.3% (53/80) of tumor tissues, which was correlated
      with tumor grade. Patients with lower expression level of HPSE mRNA or protein
      had a significantly lower survival rate than those with higher expression. Cox
      regression analysis suggested that HPSE protein was an independent predictor of
      overall survival in HCC patients. CONCLUSIONS: The results in this study
      demonstrate that genetic alteration and reduction of HPSE expression are
      associated with tumor progression and poor prognosis of HCCs, suggesting that
      HPSE behaves like a tumor suppressor gene and is a potential prognostic marker
      for HCC patients.

PMID- 22952875
TI  - Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Warfarin is a highly effective anticoagulant however its
      effectiveness relies on maintaining INR in therapeutic range. Finding the correct
      dose is difficult due to large inter-individual variability. Two genes, CYP2C9
      and VKORC1, have been associated with this variability, leading to genotype
      guided dosing tables in warfarin labeling. Nonetheless, it remains unclear how
      genotypic information should be used in practice. Navigating the literature to
      determine how genotype will influence warfarin response in a particular patient
      is difficult, due to significant variation in patient ethnicity, outcomes
      investigated, study design, and methodological rigor. Our systematic review was
      conducted to enable fair and accurate interpretation of which variants affect
      which outcomes, in which patients, and to what extent. METHODOLOGY/PRINCIPAL
      FINDINGS: A comprehensive search strategy was applied and 117 studies included.
      Primary outcomes were stable dose, time to stable dose and bleeding events.
      Methodological quality was assessed using criteria of Jorgensen and Williamson
      and data synthesized in meta-analyses using advanced methods. Pooled effect
      estimates were significant in most ethnic groups for CYP2C9*3 and stable dose
      (mutant types requiring between 1.1(0.7-1.5) and 2.3 (1.6-3.0)mg/day). Effect
      estimates were also significant for VKORC1 and stable dose for most ethnicities,
      although direction differed between asians and non-asians (mutant types requiring
      between 0.8(0.4-1.3) and 1.5(1.1-1.8)mg/day more in asians and between 1.5(0.7
      2.2) and 3.1(2.7-3.6)mg/day less in non-asians). Several studies were excluded
      due to inadequate data reporting. Assessing study quality highlighted significant
      variability in methodological rigor. Notably, there was significant evidence of
      selective reporting, of outcomes and analysis approaches.
      CONCLUSIONS/SIGNIFICANCE: Genetic associations with warfarin response vary
      between ethnicities. In order to achieve unbiased estimates in different
      populations, a high level of methodological rigor must be maintained and studies
      should report sufficient data to enable inclusion in meta-analyses. We propose
      minimum reporting requirements, suggest methodological guidelines and provide
      recommendations for reducing the risk of selective reporting.

PMID- 22952876
TI  - Cigarette smoking decreases global microRNA expression in human alveolar
      macrophages.
AB  - Human alveolar macrophages are critical components of the innate immune system.
      Cigarette smoking-induced changes in alveolar macrophage gene expression are
      linked to reduced resistance to pulmonary infections and to the development of
      emphysema/COPD. We hypothesized that microRNAs (miRNAs) could control, in part,
      the unique messenger RNA (mRNA) expression profiles found in alveolar macrophages
      of cigarette smokers. Activation of macrophages with different stimuli in vitro
      leads to a diverse range of M1 (inflammatory) and M2 (anti-inflammatory)
      polarized phenotypes that are thought to mimic activated macrophages in distinct
      tissue environments. Microarray mRNA data indicated that smoking promoted an
      "inverse" M1 mRNA expression program, defined by decreased expression of M1
      induced transcripts and increased expression of M1-repressed transcripts with few
      changes in M2-regulated transcripts. RT-PCR arrays identified altered expression
      of many miRNAs in alveolar macrophages of smokers and a decrease in global miRNA
      abundance. Stratification of human subjects suggested that the magnitude of the
      global decrease in miRNA abundance was associated with smoking history. We found
      that many of the miRNAs with reduced expression in alveolar macrophages of
      smokers were predicted to target mRNAs upregulated in alveolar macrophages of
      smokers. For example, miR-452 is predicted to target the transcript encoding
      MMP12, an important effector of smoking-related diseases. Experimental antagonism
      of miR-452 in differentiated monocytic cells resulted in increased expression of
      MMP12. The comprehensive mRNA and miRNA expression profiles described here
      provide insight into gene expression regulation that may underlie the adverse
      effects cigarette smoking has on alveolar macrophages.

PMID- 22952877
TI  - Love and suicide: the structure of the Affective Intensity Rating Scale (AIRS)
      and its relation to suicidal behavior.
AB  - BACKGROUND: Suicide has been linked to intense negative affect. However, little
      is known about the range of affects experienced by suicidal persons, or the
      separate effects of affect valence and intensity. We examine a novel self-report
      scale, the 17-item Affective Intensity Rating Scale (AIRS), and its relation to
      suicidality in a high-risk sample. METHODOLOGY/PRINCIPAL FINDINGS: Patients
      presenting with suicidality were recruited from the Emergency Department in a
      large urban hospital, and completed a battery of assessments there. Structure of
      the AIRS was assessed using Maximum Likelihood Factor Analysis with Oblimin
      rotation. Convergent and divergent validity were assessed by regressing AIRS
      subscales against Brief Symptom Inventory subscales. Relation to suicidality was
      assessed by regression of suicide attempt status against scale and subscale
      scores, and individual items and two-way item interactions, along with
      significant clinical and demographic factors. 176 subjects were included in
      analyses. Three reliable subscales were identified within the AIRS measure:
      positive feelings towards self, negative feelings towards self, and negative
      feelings towards other. Only individual AIRS items associated significantly with
      suicide attempt status; strong 'feelings of love' associated positively with
      actual suicide attempt, while 'feelings of calm' and 'positive feelings towards
      self' associated negatively. Interaction analyses suggest 'calm' moderates the
      association of 'love' with suicide attempt. CONCLUSIONS/SIGNIFICANCE: Factor
      analysis of the AIRS is consistent with a circumplex model of affect. Affective
      dimensions did not predict suicidal behavior, but intense feelings of love,
      particularly in the absence of protective feelings of calm or positive self-view
      associated with current attempt.

PMID- 22952878
TI  - Rho-ROCK and Rac-PAK signaling pathways have opposing effects on the cell-to-cell
      spread of Marek's Disease Virus.
AB  - Marek's Disease Virus (MDV) is an avian alpha-herpesvirus that only spreads from
      cell-to-cell in cell culture. While its cell-to-cell spread has been shown to be
      dependent on actin filament dynamics, the mechanisms regulating this spread
      remain largely unknown. Using a recombinant BAC20 virus expressing an EGFPVP22
      tegument protein, we found that the actin cytoskeleton arrangements and cell-cell
      contacts differ in the center and periphery of MDV infection plaques, with cells
      in the latter areas showing stress fibers and rare cellular projections. Using
      specific inhibitors and activators, we determined that Rho-ROCK pathway, known to
      regulate stress fiber formation, and Rac-PAK, known to promote lamellipodia
      formation and destabilize stress fibers, had strong contrasting effects on MDV
      cell-to-cell spread in primary chicken embryo skin cells (CESCs). Inhibition of
      Rho and its ROCKs effectors led to reduced plaque sizes whereas inhibition of Rac
      or its group I-PAKs effectors had the adverse effect. Importantly, we observed
      that the shape of MDV plaques is related to the semi-ordered arrangement of the
      elongated cells, at the monolayer level in the vicinity of the plaques.
      Inhibition of Rho-ROCK signaling also resulted in a perturbation of the cell
      arrangement and a rounding of plaques. These opposing effects of Rho and Rac
      pathways in MDV cell-to-cell spread were validated for two parental MDV
      recombinant viruses with different ex vivo spread efficiencies. Finally, we
      demonstrated that Rho/Rac pathways have opposing effects on the accumulation of N
      cadherin at cell-cell contact regions between CESCs, and defined these contacts
      as adherens junctions. Considering the importance of adherens junctions in HSV-1
      cell-to-cell spread in some cell types, this result makes of adherens junctions
      maintenance one potential and attractive hypothesis to explain the Rho/Rac
      effects on MDV cell-to-cell spread. Our study provides the first evidence that
      MDV cell-to-cell spread is regulated by Rho/Rac signaling.

PMID- 22952879
TI  - Stressor-like effects of c-Jun N-terminal kinase (JNK) inhibition.
AB  - There is an urgent need for novel treatment strategies for stressor related
      disorders, particularly depression and anxiety disorders. Indeed, existing drug
      treatments are only clinically successful in a subset of patients and relapse is
      common. This likely stems from the fact that stressor disorders are heterogeneous
      with multiple biological pathways being affected. To this end, the present
      investigation sought to assess in mice the contribution of the c-Jun N terminal
      kinase (JNK) pathway to the behavioral, hormonal and neurochemical effects of an
      acute stressor. Indeed, although JNK has been shown to modulate glucocorticoid
      receptors in vitro, virtually nothing is known of the role for JNK in affecting
      stressor induced pathology. We presently found that the JNK antagonist, SP600125,
      (but not the p38 antagonist, SB203580) increased plasma corticosterone levels
      under resting conditions and in the context of an acute stressor (wet bedding +
      restraint). SP600125 also reduced exploration in an open field arena, but
      prevented the stressor induced increase in open arm exploration in an elevated
      plus maze. Finally, SP600125 affected noradrenergic activity in the central
      amygdala and locus coruleus under resting condition, but prevented the
      noradrenergic effects within the paraventricular nucleus of the hypothalamus that
      were induced by the acute stressor exposure. These data suggest inhibiting
      endogenous JNK can have stressor-like corticoid, behavioral and central monoamine
      effects under basal conditions, but can actually reverse some behavioral and
      neurochemical effects of an acute stressor. Thus, endogenous JNK appears to
      affect stress relevant processes in a context-dependent manner.

PMID- 22952880
TI  - Improved sensitivity to cerebral white matter abnormalities in Alzheimer's
      disease with spherical deconvolution based tractography.
AB  - Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular
      approach for investigating white matter tracts in vivo, despite its inability to
      reconstruct fiber pathways in regions with "crossing fibers." Recently,
      constrained spherical deconvolution (CSD) has been developed to mitigate the
      adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the
      methodological benefit, the clinical relevance of CSD based FT for the assessment
      of white matter abnormalities remains unclear. In this work, we evaluated the
      applicability of a hybrid framework, in which CSD based FT is combined with
      conventional DTI metrics to assess white matter abnormalities in 25 patients with
      early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two
      white matter tracts: one with regions of "crossing fibers," i.e., the superior
      longitudinal fasciculus (SLF) and one which contains only one fiber orientation,
      i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics,
      fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts
      were related to memory function. Our results show that in the tract with
      "crossing fibers" the relation between FA/MD and memory was stronger with CSD
      than with DTI based FT. By contrast, in the fiber bundle where one fiber
      population predominates, the relation between FA/MD and memory was comparable
      between both tractography methods. Importantly, these associations were most
      pronounced after adjustment for the planar diffusion coefficient, a measure
      reflecting the degree of fiber organization complexity. These findings indicate
      that compared to conventionally applied DTI based FT, CSD based FT combined with
      DTI metrics can increase the sensitivity to detect functionally significant white
      matter abnormalities in tracts with complex white matter architecture.

PMID- 22952881
TI  - CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and
      promotes tumor progression.
AB  - BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and
      cellular trafficking in tumorigenesis. In this study, we report that the latest
      member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1), recruits immature
      myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL
      FINDINGS: CXCL17 was preferentially expressed in some aggressive types of
      gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart
      NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3
      cells could form vasculature-rich tumors in immunodeficient mice. Our data showed
      that CXCL17-expressing tumor cells increased immature CD11b(+)Gr1(+) myeloid
      derived cells at tumor sites in mice and promoted CD31(+) tumor angiogenesis.
      Extensive chemotactic assays proved that CXCL17-responding cells were
      CD11b(+)Gr1(high)F4/80(-) cells (~ 90%) with a neutrophil-like morphology in
      vitro. Although CXCL17 expression could not increase the number of CD11b(+)Gr1(+)
      cells in tumor-burdened SCID mice or promote metastases of low metastatic colon
      cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a
      striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE:
      These results suggest that aberrant expression of CXCL17 in tumor cells recruits
      immature myeloid-derived cells and promotes tumor progression through
      angiogenesis.

PMID- 22952882
TI  - Telomere dynamics and homeostasis in a transmissible cancer.
AB  - BACKGROUND: Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that
      threatens the world's largest carnivorous marsupial, the Tasmanian devil
      (Sarcophilus harrisii) with extinction. This transmissible cancer is passed
      between individual devils by cell implantation during social interactions. The
      tumour arose in a Schwann cell of a single devil over 15 years ago and since then
      has expanded clonally, without showing signs of replicative senescence; in stark
      contrast to a somatic cell that displays a finite capacity for replication, known
      as the "Hayflick limit". METHODOLOGY/PRINCIPAL FINDINGS: In the present study we
      investigate the role of telomere length, measured as Telomere Copy Number (TCN),
      and telomerase and shelterin gene expression, as well as telomerase activity in
      maintaining hyperproliferation of Devil Facial Tumour (DFT) cells. Our results
      show that DFT cells have short telomeres. DFTD TCN does not differ between
      geographic regions or between strains. However, TCN has increased over time.
      Unlimited cell proliferation is likely to have been achieved through the observed
      up-regulation of the catalytic subunit of telomerase (TERT) and concomitant
      activation of telomerase. Up-regulation of the central component of shelterin,
      the TRF1-intercating nuclear factor 2 (TINF2) provides DFT a mechanism for
      telomere length homeostasis. The higher expression of both TERT and TINF2 may
      also protect DFT cells from genomic instability and enhance tumour proliferation.
      CONCLUSIONS/SIGNIFICANCE: DFT cells appear to monitor and regulate the length of
      individual telomeres: i.e. shorter telomeres are elongated by up-regulation of
      telomerase-related genes; longer telomeres are protected from further elongation
      by members of the shelterin complex, which may explain the lack of spatial and
      strain variation in DFT telomere copy number. The observed longitudinal increase
      in gene expression in DFT tissue samples and telomerase activity in DFT cell
      lines might indicate a selection for more stable tumours with higher
      proliferative potential.

PMID- 22952883
TI  - Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose.
AB  - The neuronal coordination of metabolic homeostasis requires the integration of
      hormonal signals with multiple interrelated central neuronal circuits to produce
      appropriate levels of food intake, energy expenditure and fuel availability.
      Ghrelin, a peripherally produced peptide hormone, circulates at high
      concentrations during nutrient scarcity. Ghrelin promotes food intake, an action
      lost in ghrelin receptor null mice and also helps maintain fasting blood glucose
      levels, ensuring an adequate supply of nutrients to the central nervous system.
      To better understand mechanisms of ghrelin action, we have examined the roles of
      ghrelin receptor (GHSR) expression in the mouse hindbrain. Notably, selective
      hindbrain ghrelin receptor expression was not sufficient to restore ghrelin
      stimulated food intake. In contrast, the lowered fasting blood glucose levels
      observed in ghrelin receptor-deficient mice were returned to wild-type levels by
      selective re-expression of the ghrelin receptor in the hindbrain. Our results
      demonstrate the distributed nature of the neurons mediating ghrelin action.

PMID- 22952884
TI  - Characterization of cDNAs encoding serine proteases and their transcriptional
      responses to Cry1Ab protoxin in the gut of Ostrinia nubilalis larvae.
AB  - Serine proteases, such as trypsin and chymotrypsin, are the primary digestive
      enzymes in lepidopteran larvae, and are also involved in Bacillus thuringiensis
      (Bt) protoxin activation and protoxin/toxin degradation. We isolated and
      sequenced 34 cDNAs putatively encoding trypsins, chymotrypsins and their homologs
      from the European corn borer (Ostrinia nubilalis) larval gut. Our analyses of the
      cDNA-deduced amino acid sequences indicated that 12 were putative trypsins, 12
      were putative chymotrypsins, and the remaining 10 were trypsin and chymotrypsin
      homologs that lack one or more conserved residues of typical trypsins and
      chymotrypsins. Reverse transcription PCR analysis indicated that all genes were
      highly expressed in gut tissues, but one group of phylogenetically-related
      trypsin genes, OnTry-G2, was highly expressed in larval foregut and midgut,
      whereas another group, OnTry-G3, was highly expressed in the midgut and hindgut.
      Real-time quantitative PCR analysis indicated that several trypsin genes (OnTry5
      and OnTry6) were significantly up-regulated in the gut of third-instar larvae
      after feeding on Cry1Ab protoxin from 2 to 24 h, whereas one trypsin (OnTry2) was
      down-regulated at all time points. Four chymotrypsin and chymotrypsin homolog
      genes (OnCTP2, OnCTP5, OnCTP12 and OnCTP13) were up-regulated at least 2-fold in
      the gut of the larvae after feeding on Cry1Ab protoxin for 24 h. Our data
      represent the first in-depth study of gut transcripts encoding expanded families
      of protease genes in O. nubilalis larvae and demonstrate differential expression
      of protease genes that may be related to Cry1Ab intoxication and/or resistance.

PMID- 22952885
TI  - Novel direct targets of miR-19a identified in breast cancer cells by a
      quantitative proteomic approach.
AB  - The miR-17-92 cluster encodes 7 miRNAs inside a single polycistronic transcript,
      and is known as a group of oncogenic miRNAs that contribute to tumorigenesis in
      several cancers. However, their direct targets remain unclear, and it has been
      suggested that a single miRNA is capable of reducing the production of hundreds
      of proteins. The majority of reports on the identification of miRNA targets are
      based on computational approaches or the detection of altered mRNA levels,
      despite the fact that most miRNAs are thought to regulate their targets primarily
      by translational inhibition in higher organisms. In this study, we examined the
      target profiles of miR-19a, miR-20a and miR-92-1 in MCF-7 breast cancer cells by
      a quantitative proteomic strategy to identify their direct targets. A total of
      123 proteins were significantly increased after the endogenous miR-19a, miR-20a
      and miR-92-1 were knocked down, and were identified as potential targets by two
      dimensional electrophoresis and a mass spectrometric analysis. Among the
      upregulated proteins, four (PPP2R2A, ARHGAP1, IMPDH1 and NPEPL1) were shown to
      have miR-19a or miR-20a binding sites on their mRNAs. The luciferase activity of
      the plasmids with each binding site was observed to decrease, and an increased
      luciferase activity was observed in the presence of the specific anti-miRNA-LNA.
      A Western blot analysis showed the expression levels of IMPDH1 and NPEPL1 to
      increase after treatment with anti-miR-19a, while the expression levels of
      PPP2R2A and ARHGAP1 did not change. The expression levels of IMPDH1 and NPEPL1
      did not significantly change by anti-miR-19a-LNA at the mRNA level. These results
      suggest that the IMPDH1 and NPEPL1 genes are direct targets of miR-19a in breast
      cancer, while the exogenous expression of these genes is not associated with the
      growth suppression of MCF-7 cells. Furthermore, our proteomic approaches were
      shown to be valuable for identifying direct miRNA targets.

PMID- 22952886
TI  - Association of educational, occupational and socioeconomic status with
      cardiovascular risk factors in Asian Indians: a cross-sectional study.
AB  - BACKGROUND: To determine correlation of multiple parameters of socioeconomic
      status with cardiovascular risk factors in India. METHODS: The study was
      performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426,
      women 2772) were evaluated for socioeconomic, demographic, biophysical and
      biochemical factors. They were classified into low, medium and high socioeconomic
      groups based on educational level (<10, 10-15 and >15 yr formal education),
      occupational class and socioeconomic scale. Risk factor differences were
      evaluated using multivariate logistic regression. RESULTS: Age-adjusted
      prevalence (%) of risk factors in men and women was overweight or obesity in 41.1
      and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high
      waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia
      24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and
      31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent.
      Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high
      fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and
      physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was
      significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%)
      educational groups (p<0.01). In low vs. high educational groups there was greater
      prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65
      2.71), low HDL cholesterol (1.51, 1.27-1.80), hypertriglyceridemia (1.16, 0.99
      1.37), smoking/tobacco use (3.27, 2.66-4.01), and low physical activity (1.15,
      0.97-1.37); and lower prevalence of high fat diet (0.47, 0.38
      0.57),overweight/obesity (0.68, 0.58-0.80) and hypercholesterolemia (0.79, 0.66
      0.94). Similar associations were observed with occupational and socioeconomic
      status. CONCLUSIONS: Low educational, occupational and socioeconomic status Asian
      Indians have greater prevalence of truncal obesity, low HDL cholesterol,
      hypertriglyceridemia, smoking or tobacco use and low physical activity and
      clustering of > = 3 major cardiovascular risk factors.

PMID- 22952887
TI  - A genetic mechanism for emergence of races in Fusarium oxysporum f. sp.
      lycopersici: inactivation of avirulence gene AVR1 by transposon insertion.
AB  - Compatible/incompatible interactions between the tomato wilt fungus Fusarium
      oxysporum f. sp. lycopersici (FOL) and tomato Solanum lycopersicum are controlled
      by three avirulence genes (AVR1-3) in FOL and the corresponding resistance genes
      (I-I3) in tomato. The three known races (1, 2 and 3) of FOL carry AVR genes in
      different combinations. The current model to explain the proposed order of
      mutations in AVR genes is: i) FOL race 2 emerged from race 1 by losing the AVR1
      and thus avoiding host resistance mediated by I (the resistance gene
      corresponding to AVR1), and ii) race 3 emerged when race 2 sustained a point
      mutation in AVR2, allowing it to evade I2-mediated resistance of the host. Here,
      an alternative mechanism of mutation of AVR genes was determined by analyses of a
      race 3 isolate, KoChi-1, that we recovered from a Japanese tomato field in 2008.
      Although KoChi-1 is race 3, it has an AVR1 gene that is truncated by the
      transposon Hormin, which belongs to the hAT family. This provides evidence that
      mobile genetic elements may be one of the driving forces underlying race
      evolution. KoChi-1 transformants carrying a wild type AVR1 gene from race 1 lost
      pathogenicity to cultivars carrying I, showing that the truncated KoChi-1 avr1 is
      not functional. These results imply that KoChi-1 is a new race 3 biotype and
      propose an additional path for emergence of FOL races: Race 2 emerged from race 1
      by transposon-insertion into AVR1, not by deletion of the AVR1 locus; then a
      point mutation in race 2 AVR2 resulted in emergence of race 3.

PMID- 22952889
TI  - Exploring bacterial diversity in hospital environments by GS-FLX Titanium
      pyrosequencing.
AB  - Understanding microbial populations in hospital environments is crucial for
      improving human health. Hospital-acquired infections are an increasing problem in
      intensive care units (ICU). In this work we present an exploration of bacterial
      diversity at inanimate surfaces of the ICU wards of the University Hospital A
      Coruna (Spain), as an example of confined hospital environment subjected to
      selective pressure, taking the entrance hall of the hospital, an open and crowded
      environment, as reference. Surface swab samples were collected from both
      locations and recovered DNA used as template to amplify a hypervariable region of
      the bacterial 16S rRNA gene. Sequencing of the amplicons was performed at the
      Roche 454 Sequencing Center using GS-FLX Titanium procedures. Reads were pre
      processed and clustered into OTUs (operational taxonomic units), which were
      further classified. A total of 16 canonical bacterial phyla were detected in both
      locations. Members of the phyla Firmicutes (mainly Staphylococcus and
      Streptococcus) and Actinobacteria (mainly Micrococcaceae, Corynebacteriaceae and
      Brevibacteriaceae) were over-represented in the ICU with respect to the Hall. The
      phyllum Proteobacteria was also well represented in the ICU, mainly by members of
      the families Enterobacteriaceae, Methylobacteriaceae and Sphingomonadaceae. In
      the Hall sample, the phyla Proteobacteria, Bacteroidetes, Deinococcus-Thermus and
      Cyanobacteria were over-represented with respect to the ICU. Over-representation
      of Proteobacteria was mainly due to the high abundance of Enterobacteriaceae
      members. The presented results demonstrate that bacterial diversity differs at
      the ICU and entrance hall locations. Reduced diversity detected at ICU, relative
      to the entrance hall, can be explained by its confined character and by the
      existence of antimicrobial selective pressure. This is the first study using deep
      sequencing techniques made in hospital wards showing substantial hospital
      microbial diversity.

PMID- 22952888
TI  - Laboratory-based surveillance of Neisseria meningitidis isolates from disease
      cases in Latin American and Caribbean countries, SIREVA II 2006-2010.
AB  - BACKGROUND: Published data on the epidemiology of meningococcal disease in Latin
      America and the Caribbean region is scarce and, when available, it is often
      published in Spanish and/or in non-peer-reviewed journals, making it difficult
      for the international scientific community to have access. METHODS: Laboratory
      data on 4,735 Neisseria meningitidis strains was collected and reported by the
      National Reference Laboratories in 19 Latin American countries and the Caribbean
      Epidemiology Centre (CAREC) between 2006 and 2010 as part of the work carried out
      by the SIREVA II network. Serogroup and MIC to penicillin, rifampin and
      chloramphenicol were determined. RESULTS: Isolates were mainly obtained from
      patients <5 years, but each year around 25% of isolates came from adult patients.
      Serogroup distribution was highly variable among countries. Serogroup C was the
      main cause of disease in Brazil; the majority of disease seen in the Southern
      cone was caused by serogroup B, but serogroup W135 strains have increased in
      recent years. In the Andean and Mexico, Central America and Caribbean regions,
      serogroups B and C were equally present, and serogroup Y was frequently isolated.
      Isolates were generally susceptible to chloramphenicol, penicillin and rifampin,
      but almost 60% of isolates characterized in Southern cone countries presented
      intermediate resistance to penicillin. Five rifampin-resistant isolates have been
      isolated in Uruguay and Brazil. CONCLUSIONS: Serogroup distribution is highly
      variable among countries, but some geographic structuring can be inferred from
      these data. Epidemiological and laboratory data are scarce among Andean and
      Mexico, Central America and Caribbean countries. Evaluation and implementation of
      corrective measures on disease surveillance and reporting systems and the
      implementation of molecular diagnostic techniques and molecular characterization
      on meningococcal isolates are advised.

PMID- 22952891
TI  - Improvement of tuberculosis laboratory capacity on Pemba Island, Zanzibar: a
      health cooperation project.
AB  - Low-income countries with high Tuberculosis burden have few reference
      laboratories able to perform TB culture. In 2006, the Zanzibar National TB
      Control Programme planned to decentralize TB diagnostics. The Italian Cooperation
      Agency with the scientific support of the "L. Spallanzani" National Institute for
      Infectious Diseases sustained the project through the implementation of a TB
      reference laboratory in a low-income country with a high prevalence of TB. The
      implementation steps were: 1) TB laboratory design according to the WHO
      standards; 2) laboratory equipment and reagent supplies for microscopy, cultures,
      and identification; 3) on-the-job training of the local staff; 4) web- and
      telemedicine-based supervision. From April 2007 to December 2010, 921 sputum
      samples were received from 40 peripheral laboratories: 120 TB cases were
      diagnosed. Of all the smear-positive cases, 74.2% were culture-positive. During
      the year 2010, the smear positive to culture positive rate increased up to 100%.
      In March 20, 2010 the Ministry of Health and Social Welfare of Zanzibar
      officially recognized the Public Health Laboratory- Ivo de Carneri as the
      National TB Reference Laboratory for the Zanzibar Archipelago. An advanced TB
      laboratory can represent a low cost solution to strengthen the TB diagnosis, to
      provide capacity building and mid-term sustainability.

PMID- 22952890
TI  - Resveratrol inhibits LPS-induced MAPKs activation via activation of the
      phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells.
AB  - BACKGROUND: Resveratrol is a natural polyphenolic compound that has
      cardioprotective, anticancer and anti-inflammatory properties. We investigated
      the capacity of resveratrol to protect RAW 264.7 cells from inflammatory insults
      and explored mechanisms underlying inhibitory effects of resveratrol on RAW 264.7
      cells. METHODOLOGY/PRINCIPAL FINDINGS: Murine RAW 264.7 cells were treated with
      resveratrol (1, 5, and 10 uM) and/or LPS (5 ug/ml). Nitric oxide (NO) and
      prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and
      protein levels of proinflammatory proteins and cytokines were analysed by ELISA,
      RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation
      levels of Akt, cyclic AMP-responsive element-binding protein (CREB), mitogen
      activated protein kinases (MAPKs) cascades, AMP-activated protein kinase (AMPK)
      and expression of SIRT1(Silent information regulator T1) were measured by western
      blot. Wortmannin (1 uM), a specific phosphatidylinositol 3-kinase (PI3-K)
      inhibitor, was used to determine if PI3-K/Akt signaling pathway might be involved
      in resveratrol's action on RAW 264.7 cells. Resveratrol significantly attenuated
      the LPS-induced expression of nitric oxide (NO), prostaglandin E2 (PGE2),
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in RAW 264.7 cells.
      Resveratrol increased Akt phosphorylation in a time-dependent manner. Wortmannin,
      a specific phosphatidylinositol 3-kinase (PI3-K) inhibitor, blocked the effects
      of resveratrol on LPS-induced RAW 264.7 cells activation. In addition, PI3-K
      inhibition partially abolished the inhibitory effect of resveratrol on the
      phosphorylation of cyclic AMP-responsive element-binding protein (CREB) and
      mitogen-activated protein kinases (MAPKs) cascades. Meanwhile, PI3-K is essential
      for resveratrol-mediated phosphorylation of AMPK and expression of SIRT1.
      CONCLUSION AND IMPLICATIONS: This investigation demonstrates that PI3-K/Akt
      activation is an important signaling in resveratrol-mediated activation of AMPK
      phosphorylation and SIRT1 expression, and inhibition of phosphorylation of CREB
      and MAPKs activation, proinflammatory mediators and cytokines production in
      response to LPS in RAW 264.7 cells.

PMID- 22952892
TI  - Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine
      origin influenza A (H1N1) virus in mice.
AB  - BACKGROUND: The 2009 influenza pandemic affected people in almost all countries
      in the world, especially in younger age groups. During this time, the debate over
      whether to use corticosteroid treatment in severe influenza H1N1 infections
      patients resurfaced and was disputed by clinicians. There is an urgent need for a
      susceptible animal model of 2009 H1N1 infection that can be used to evaluate the
      pathogenesis and the therapeutic effect of corticosteroid treatment during
      infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups
      of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice) to compare the
      pathogenesis of several different H1N1 strains in mice of different ages. Based
      on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501
      strain of 2009 H1N1 virus infection was established, showing significantly
      elevated lung edema and cytokine levels compared to controls. Using our
      established animal model, the cytokine production profile and lung histology were
      assessed at different times post-infection, revealing increased lung lesions in a
      time-dependent manner. In additional,the mice were also treated with
      dexamethasone, which significantly improved survival rate and lung lesions in
      infected mice compared to those in control mice. Our data showed that
      corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1
      virus in mice and suggested that corticosteroids are valid drugs for treating
      2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very
      susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate
      that corticosteroids are a potential therapeutic remedy that may address the
      increasing concerns over future 2009 A/H1N1 pandemics.

PMID- 22952893
TI  - Effect of different ammonia concentrations on community succession of ammonia
      oxidizing microorganisms in a simulated paddy soil column.
AB  - Ammonia oxidation is performed by both ammonia-oxidizing bacteria (AOB) and
      ammonia-oxidizing archaea (AOA). To explore the effect of ammonia concentration
      on the population dynamic changes of ammonia-oxidizing microorganisms, we
      examined changes in the abundance and community composition of AOA and AOB in
      different layers. Most of the archaeal amoA sequences were Nitrosotalea-related
      and the proportion that Nitrosotalea cluster occupied decreased in the surface
      layer and increased in the deep layer during the cultivation process.
      Nitrosopumilus-related sequences were only detected in the deep layer in the
      first stage and disappeared later. Both phylogenetic and quantitative analysis
      showed that there were increased Nitrosomonas-related sequences appeared in the
      surface layer where the ammonia concentration was the highest. Both AOA and AOB
      OTU numbers in different layers decreased under selective pressure and then
      recovered. The potential nitrification rates were 25.06 ug . N . L(-1) . g(-1)
      dry soil . h(-1) in the mid layer which was higher than the other two layers. In
      general, obvious population dynamic changes were found for both AOA and AOB under
      the selective pressure of exogenous ammonia and the changes were different in
      three layers of the soil column.

PMID- 22952894
TI  - Effective gene trapping mediated by Sleeping Beauty transposon.
AB  - Gene trapping is a high-throughput approach to elucidate gene functions by
      disrupting and recapitulating expression of genes in a target genome. A number of
      transposon-based gene-trapping systems are developed for mutagenesis in cells and
      model organisms, but there is still much room for the improvement of their
      efficiency in gene disruption and mutation. Herein, a gene-trapping system
      mediated by Sleeping Beauty (SB) transposon was developed by inclusion of three
      functional cassettes. The mutation cassette can abrogate the splice of trapped
      genes and terminate their translation. Once an endogenous gene is captured, the
      finding cassette independently drives the translation of reporter gene in HeLa
      cells and zebrafish embryos. The efficiency cassette controls the remobilization
      of integrated traps through inducible expression of SB gene. Analysis of
      transposon-genome junctions indicate that most of trap cassettes are integrated
      into an intron without an obvious 3' bias. The transcription of trapped genes was
      abrogated by alternative splicing of the mutation cassette. In addition,
      integrated transposons can be induced to excise from their original insertion
      sites. Furthermore, the Cre/LoxP system was introduced to delete the efficiency
      cassette for stabilization of gene interruption and bio-safety. Thus, this gene
      trap vector is an alternative and effective tool for the capture and disruption
      of endogenous genes in vitro and in vivo.

PMID- 22952895
TI  - Transcriptional regulation of mouse PXR gene: an interplay of transregulatory
      factors.
AB  - Pregnane X Receptor (PXR) is an important ligand-activated nuclear receptor
      functioning as a 'master regulator' of expression of phase I, phase II drug
      metabolizing enzymes, and members of the drug transporters. PXR is primarily
      expressed in hepatic tissues and to lesser extent in other non-hepatic tissues
      both in human and in mice. Although its expression profile is well studied but
      little is known about the regulatory mechanisms that govern PXR gene expression
      in these cells. In the present study, we have cloned and characterized over 5 kb
      (-4963 to +54) region lying upstream of mouse PXR transcription start site.
      Promoter-reporter assays revealed that the proximal promoter region of up to 1 kb
      is sufficient to support the expression of PXR in the mouse liver cell lines. It
      was evident that the 500 bp proximal promoter region contains active binding
      sites for Ets, Tcf, Ikarose and nuclear factor families of transcription factors.
      Electrophoretic mobility shift assays demonstrated that the minimal region of 134
      bp PXR promoter was able to bind Ets-1 and beta-catenin proteins. This result was
      further confirmed by chromatin immunoprecipitation analysis. In summary, the
      present study identified a promoter region of mouse PXR gene and the
      transregulatory factors responsible for PXR promoter activity. The results
      presented herein are expected to provide important cues to gain further insight
      into the regulatory mechanisms of PXR function.

PMID- 22952896
TI  - A resealed-cell system for analyzing pathogenic intracellular events:
      perturbation of endocytic pathways under diabetic conditions.
AB  - Cell-based assay systems that can serve as cellular models of aberrant function
      in pathogenic organs would be novel and useful tools for screening drugs and
      clarifying the molecular mechanisms of various diseases. We constructed model
      cells that replicated the conditions in diabetic hepatocytes by using the cell
      resealing technique, which enables the exchange of cytosol. The plasma membrane
      of HeLa cells was permeabilized with the streptococcal toxin streptolysin O, and
      cytosol that had been prepared from wild-type or db/db diabetic mice was
      introduced into the resulting semi-intact cells. By resealing the plasma membrane
      by exposure to Ca(2+), we created WT or Db model cells, in which the cytosolic
      conditions replicated those of healthy or diabetic liver. Interestingly,
      phosphorylation of p38 MAPK was promoted, whereas the level of endosomal
      phosphatidylinositol-3-phosphate was decreased, in Db cells. We investigated
      several endocytic pathways in WT and Db cells, and found that retrograde endosome
      to-Golgi transport was delayed in a p38 MAPK-dependent manner in Db cells.
      Furthermore, the degradation pathway of the EGF receptor from endosomes to
      lysosomes was enhanced in Db cells, and this did not depend on the activation of
      p38 MAPK. The disease model cell system should become a powerful tool for the
      detection of aberrant processes in cells under pathogenic conditions and for
      therapeutic applications.

PMID- 22952898
TI  - Do implicit attitudes predict actual voting behavior particularly for undecided
      voters?
AB  - The prediction of voting behavior of undecided voters poses a challenge to
      psychologists and pollsters. Recently, researchers argued that implicit attitudes
      would predict voting behavior particularly for undecided voters whereas explicit
      attitudes would predict voting behavior particularly for decided voters. We
      tested this assumption in two studies in two countries with distinct political
      systems in the context of real political elections. Results revealed that (a)
      explicit attitudes predicted voting behavior better than implicit attitudes for
      both decided and undecided voters, and (b) implicit attitudes predicted voting
      behavior better for decided than undecided voters. We propose that greater
      elaboration of attitudes produces stronger convergence between implicit and
      explicit attitudes resulting in better predictive validity of both, and less
      incremental validity of implicit over explicit attitudes for the prediction of
      voting behavior. However, greater incremental predictive validity of implicit
      over explicit attitudes may be associated with less elaboration.

PMID- 22952897
TI  - The WHO maternal near-miss approach and the maternal severity index model (MSI):
      tools for assessing the management of severe maternal morbidity.
AB  - OBJECTIVES: To validate the WHO maternal near-miss criteria and develop a
      benchmark tool for severe maternal morbidity assessments. METHODS: In a
      multicenter cross-sectional study implemented in 27 referral maternity hospitals
      in Brazil, a one-year prospective surveillance on severe maternal morbidity and
      data collection was carried out. Diagnostic accuracy tests were used to assess
      the validity of the WHO maternal near-miss criteria. Binary logistic regression
      was used to model the death probability among women with severe maternal
      complications and benchmark the management of severe maternal morbidity. RESULTS:
      Of the 82,388 women having deliveries in the participating health facilities,
      9,555 women presented pregnancy-related complications, including 140 maternal
      deaths and 770 maternal near misses. The WHO maternal near-miss criteria were
      found to be accurate and highly associated with maternal deaths (Positive
      likelihood ratio 106.8 (95% CI 99.56-114.6)). The maternal severity index (MSI)
      model was developed and found to able to describe the relationship between life
      threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI
      0.909-0.993)). CONCLUSION: The identification of maternal near-miss cases using
      the WHO list of pregnancy-related life-threatening conditions was validated. The
      MSI model can be used as a tool for benchmarking the performance of health
      services managing women with severe maternal complications and provide case-mix
      adjustment.

PMID- 22952899
TI  - The largely normal response to Toll-like receptor 7 and 9 stimulation and the
      enhanced expression of SIGIRR by B cells in systemic lupus erythematosus.
AB  - BACKGROUND: Altered Toll-like receptor (TLR) signaling has been implicated in the
      pathogenesis of systemic lupus erythematosus (SLE). The present study was
      undertaken to characterize responses of B cells from SLE patients to TLR7 and
      TLR9 stimulation and to explore the potential role of single immunoglobulin
      interleukin-1 receptor related molecule (SIGIRR) in the regulation of TLR
      mediated responses of SLE B cells. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral
      blood mononuclear cells (PBMC) were isolated from 64 patients with SLE and 37
      healthy donors. CD19+ B cells purified using microbeads were cultured with TLR7
      or TLR9 agonists. Cell proliferation was measured by thymine incorporation and
      the frequency of antibody-secreting cells was determined by ELISPOT assay. SIGIRR
      expression in PBMCs and B cells was analyzed using flow cytometry analysis. In
      contrast to the enhanced proliferation following B cell receptor (BCR)
      engagement, B cells from SLE patients exhibited a virtually normal proliferative
      response to TLR7 or TLR9 stimulation. Moreover, B cells from SLE patients and
      healthy donors were almost equally competent to differentiate into antibody
      secreting cells upon TLR engagement except for a reduction in the generation of
      IgG-secreting cells by TLR9-stimulated lupus B cells. In line with these somehow
      unexpected observations, SLE B cells were found to express a significantly higher
      level of SIGIRR than normal B cells. CONCLUSIONS/SIGNIFICANCE: Despite the
      reported upregulation of TLR7 and TLR9 expression in B cell from SLE patients,
      their responses to TLR stimulation were largely normal. The increased expression
      of the negative regulator SIGIRR may be partly responsible for the "balance of
      terror".

PMID- 22952900
TI  - Improved consistency in dosing anti-tuberculosis drugs in Taipei, Taiwan.
AB  - BACKGROUND: It was reported that 35.5% of tuberculosis (TB) cases reported in
      2003 in Taipei City had no recorded pre-treatment body weight and that among
      those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers
      for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB
      drugs among general practitioners. Prescribing practices of anti-TB drugs in
      Taipei City in 2007-2010 were investigated to assess whether interventions on
      dosing were effective. METHODOLOGY/PRINCIPAL FINDINGS: Lists of all notified
      culture positive TB cases in 2007-2010 were obtained from National TB Registry at
      Taiwan CDC. A medical audit of TB case management files was performed to collect
      pretreatment body weight and regimens prescribed at commencement of treatment.
      Dosages prescribed were compared with dosages recommended. The proportion of
      patients with recorded pre-treatment body weight was 64.5% in 2003, which
      increased to 96.5% in 2007-2010 (p<0.001). The proportion of patients treated
      with consistent dosing of a 3-drug fixed-dose combination (FDC) increased from
      73.9% in 2003 to 87.7% in 2007-2010 (p<0.001), and that for 2-drug FDC from 76.0%
      to 86.1% (p = 0.024), for rifampicin (RMP) from 62.8% to 85.5% (p<0.001), and for
      isoniazid from 87.8% to 95.3% (p<0.001). In 2007-2010, among 2917 patients
      treated with either FDCs or RMP in single-drug preparation, the dosage of RMP was
      adequate (8-12 mg/kg) in 2571(88.1%) patients, too high in 282(9.7%), too low in
      64(2.2%). In multinomial logistic regression models, factors significantly
      associated with adequate dosage of RMP were body weight and preparations of RMP.
      Patients weighting <40 kg (relative risk ratio (rrr) 6010.5, 95% CI 781.1
      46249.7) and patients weighting 40-49 kg (rrr 1495.3, 95% CI 200.6-11144.6) were
      more likely to receive higher-than-recommended dose of RMP.
      CONCLUSIONS/SIGNIFICANCE: Prescribing practice in the treatment of TB in Taipei
      City has remarkably improved after health authorities implemented a series of
      interventions.

PMID- 22952901
TI  - Association between serum growth hormone levels and nonalcoholic fatty liver
      disease: a cross-sectional study.
AB  - Growth hormone (GH) is an important regulator of metabolism and body composition.
      GH deficiency is associated with increased visceral body fat and other features
      of the metabolic syndrome. Here we performed a cross-sectional study to explore
      the association of GH levels with nonalcoholic fatty liver disease (NAFLD), which
      is considered to be the hepatic manifestation of the metabolic syndrome. A total
      of 1,667 subjects were diagnosed as NAFLD according the diagnostic criteria, and
      5,479 subjects were defined as the controls. The subjects with NAFLD had
      significantly lower levels of serum GH than the controls. Those with low GH
      levels had a higher prevalence of NAFLD and the metabolic syndrome. A stepwise
      logistic regression analysis showed that GH levels were significantly associated
      with the risk factor for NAFLD (OR = 0.651, 95%CI = 0.574-0.738, P<0.001). Our
      results showed a significant association between lower serum GH levels and NAFLD.

PMID- 22952902
TI  - Ultraviolet irradiation-dependent fluorescence enhancement of hemoglobin
      catalyzed by reactive oxygen species.
AB  - Ultraviolet (UV) light has a potent effect on biological organisms. Hemoglobin,
      an oxygen-transport protein, plays an irreplaceable role in sustaining life of
      all vertebrates. In this study we scrutinize the effects of ultraviolet
      irradiation (UVI) as well as visible irradiation on the fluorescence
      characteristics of bovine hemoglobin (BHb) in vitro. Data show that UVI results
      in fluorescence enhancement of BHb in a dose-dependent manner. Furthermore, UVI
      induced fluorescence enhancement is significantly increased when BHb is
      pretreated with hydrogen peroxide (H(2)O(2)), a type of reactive oxygen species
      (ROS). Meanwhile, The water-soluble antioxidant vitamin C suppresses this UVI
      induced fluorescence enhancement. In contrast, green light irradiation does not
      lead to fluorescence enhancement of BHb no matter whether H(2)O(2) is acting on
      the BHb solution or not. Taken together, these results indicate that catalysis of
      ROS and UVI-dependent irradiation play two key roles in the process of UVI
      induced fluorescence enhancement of BHb.

PMID- 22952903
TI  - K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K
      inhibition in vivo.
AB  - Activating K-RAS mutations occur at a frequency of 90% in pancreatic cancer, and
      to date no therapies exist targeting this oncogene. K-RAS signals via downstream
      effector pathways such as the MAPK and the PI3K signaling pathways, and much
      effort has been focused on developing drugs targeting components of these
      pathways. To better understand the requirements for K-RAS and its downstream
      signaling pathways MAPK and PI3K in pancreatic tumor maintenance, we established
      an inducible K-RAS knock down system that allowed us to ablate K-RAS in
      established tumors. Knock down of K-RAS resulted in impaired tumor growth in all
      pancreatic xenograft models tested, demonstrating that K-RAS expression is indeed
      required for tumor maintenance of K-RAS mutant pancreatic tumors. We further
      examined signaling downstream of K-RAS, and detected a robust reduction of pERK
      levels upon K-RAS knock down. In contrast, no effect on pAKT levels could be
      observed due to almost undetectable basal expression levels. To investigate the
      requirement of the MAPK and the PI3K pathways on tumor maintenance, three
      selected pancreatic xenograft models were tested for their response to MEK or
      PI3K inhibition. Tumors of all three models regressed upon MEK inhibition, but
      showed less pronounced response to PI3K inhibition. The effect of MEK inhibition
      on pancreatic xenografts could be enhanced further by combined application of a
      PI3K inhibitor. These data provide further rationale for testing combinations of
      MEK and PI3K inhibitors in clinical trials comprising a patient population with
      pancreatic cancer harboring mutations in K-RAS.

PMID- 22952904
TI  - Fatigue and muscle atrophy in a mouse model of myasthenia gravis is paralleled by
      loss of sarcolemmal nNOS.
AB  - Myasthenia Gravis (MG) patients suffer from chronic fatigue of skeletal muscles,
      even after initiation of proper immunosuppressive medication. Since the
      localization of neuronal nitric oxide synthase (nNOS) at the muscle membrane is
      important for sustained muscle contraction, we here study the localization of
      nNOS in muscles from mice with acetylcholine receptor antibody seropositive
      (AChR+) experimental autoimmune MG (EAMG). EAMG was induced in 8 week-old male
      mice by immunization with AChRs purified from torpedo californica. Sham-injected
      wild type mice and mdx mice, a model for Duchenne muscular dystrophy, were used
      for comparison. At EAMG disease grade 3 (severe myasthenic weakness), the
      triceps, sternomastoid and masseter muscles were collected for analysis. Unlike
      in mdx muscles, total nNOS expression as well as the presence of its binding
      partner syntrophin alpha-1, were not altered in EAMG. Immunohistological and
      biochemical analysis showed that nNOS was lost from the muscle membrane and
      accumulated in the cytosol, which is likely the consequence of blocked
      neuromuscular transmission. Atrophy of all examined EAMG muscles were supported
      by up-regulated transcript levels of the atrogenes atrogin-1 and MuRF1, as well
      as MuRF1 protein, in combination with reduced muscle fiber diameters. We propose
      that loss of sarcolemmal nNOS provides an additional mechanism for the chronic
      muscle fatigue and secondary muscle atrophy in EAMG and MG.

PMID- 22952905
TI  - Environmental enrichment alters nicotine-mediated locomotor sensitization and
      phosphorylation of DARPP-32 and CREB in rat prefrontal cortex.
AB  - Exposure within an environmental enrichment paradigm results in neurobiological
      adaptations and decreases the baseline of locomotor activity. The current study
      determined activation of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein
      32) and CREB (cAMP response element binding protein), and locomotor activity in
      rats raised in enriched (EC), impoverished (IC), and standard (SC) conditions
      following repeated administration of nicotine or saline. In the saline-control
      group, the basal phosphorylation state of DARPP-32 at Threonine-34 site (pDARPP
      32 Thr34) in the prefrontal cortex (PFC) was lower in EC compared to IC and SC
      rats, which was positively correlated with their respective baseline activities.
      While nicotine (0.35 mg/kg, freebase) produced locomotor sensitization across all
      housing conditions when the nicotine-mediated locomotor activity was expressed as
      a percent change from their respective saline control, EC rats displayed greater
      sensitization to nicotine than IC and SC rats. Consistent with the behavioral
      findings, repeated nicotine injection increased pDARPP-32 Thr34 in PFC of EC and
      IC rats and in nucleus accumbens of EC rats; however, the magnitude of change
      from saline control in nicotine-induced enhancement of pDARPP-32 Thr34 in PFC was
      strikingly increased in EC rats relative to IC rats. Moreover, EC rats had lower
      basal phosphorylation levels of CREB at serine 133 in PFC and nucleus accumbens
      compared to IC and SC rats, whereas the nicotine-induced increase in
      phosphorylated CREB-Ser133 was more pronounced in PFC of EC rats relative to IC
      and SC rats. Collectively, these findings suggest innovative insights into
      advancing our understanding of the molecular mechanisms of enrichment-induced
      changes in the motivational effects of nicotine, and aiding in the identification
      of new therapeutic strategies for tobacco smokers.

PMID- 22952906
TI  - Dynamin- and Rab5-dependent endocytosis of a Ca2+ -activated K+ channel, KCa2.3.
AB  - Regulation of the number of ion channels at the plasma membrane is a critical
      component of the physiological response. We recently demonstrated that the Ca(2+)
      activated K(+) channel, KCa2.3 is rapidly endocytosed and enters a Rab35- and
      EPI64C-dependent recycling compartment. Herein, we addressed the early endocytic
      steps of KCa2.3 using a combination of fluorescence and biotinylation techniques.
      We demonstrate that KCa2.3 is localized to caveolin-rich domains of the plasma
      membrane using fluorescence co-localization, transmission electron microscopy and
      co-immunoprecipitation (co-IP). Further, in cells lacking caveolin-1, we observed
      an accumulation of KCa2.3 at the plasma membrane as well as a decreased rate of
      endocytosis, as assessed by biotinylation. We also demonstrate that KCa2.3 and
      dynamin II are co-localized following endocytosis as well as demonstrating they
      are associated by co-IP. Further, expression of K44A dynamin II resulted in a 2
      fold increase in plasma membrane KCa2.3 as well as a 3-fold inhibition of
      endocytosis. Finally, we evaluated the role of Rab5 in the endocytosis of KCa2.3.
      We demonstrate that expression of a dominant active Rab5 (Q79L) results in the
      accumulation of newly endocytosed KCa2.3 on to the membrane of the Rab5-induced
      vacuoles. We confirmed this co-localization by co-IP; demonstrating that KCa2.3
      and Rab5 are associated. As expected, if Rab5 is required for the endocytosis of
      KCa2.3, expression of a dominant negative Rab5 (S34N) resulted in an approximate
      2-fold accumulation of KCa2.3 at the plasma membrane. This was confirmed by siRNA
      mediated knockdown of Rab5. Expression of the dominant negative Rab5 also
      resulted in a decreased rate of KCa2.3 endocytosis. These results demonstrate
      that KCa2.3 is localized to a caveolin-rich domain within the plasma membrane and
      is endocytosed in a dynamin- and Rab5-dependent manner prior to entering the
      Rab35/EPI64C recycling compartment and returning to the plasma membrane.

PMID- 22952907
TI  - StarD7 knockdown modulates ABCG2 expression, cell migration, proliferation, and
      differentiation of human choriocarcinoma JEG-3 cells.
AB  - BACKGROUND: StAR-related lipid transfer domain containing 7 (StarD7) is a member
      of the START-domain protein family whose function still remains unclear. Our data
      from an explorative microarray assay performed with mRNAs from StarD7 siRNA
      transfected JEG-3 cells indicated that ABCG2 (ATP-binding cassette sub-family G
      member 2) was one of the most abundantly downregulated mRNAs.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we have confirmed that knocking down StarD7
      mRNA lead to a decrease in the xenobiotic/lipid transporter ABCG2 at both the
      mRNA and protein levels (-26.4% and -41%, p<0.05, at 48 h of culture,
      respectively). Also a concomitant reduction in phospholipid synthesis,
      bromodeoxyuridine (BrdU) uptake and (3)H-thymidine incorporation was detected.
      Wound healing and transwell assays revealed that JEG-3 cell migration was
      significantly diminished (p<0.05). Conversely, biochemical differentiation
      markers such as human chorionic gonadotrophin beta-subunit (betahCG) protein
      synthesis and secretion as well as betahCG and syncytin-1 mRNAs were increased
      approximately 2-fold. In addition, desmoplakin immunostaining suggested that
      there was a reduction of intercellular desmosomes between adjacent JEG-3 cells
      after knocking down StarD7. CONCLUSIONS/SIGNIFICANCE: Altogether these findings
      provide evidence for a role of StarD7 in cell physiology indicating that StarD7
      modulates ABCG2 multidrug transporter level, cell migration, proliferation, and
      biochemical and morphological differentiation marker expression in a human
      trophoblast cell model.

PMID- 22952908
TI  - IL-22 signaling contributes to West Nile encephalitis pathogenesis.
AB  - The Th17 cytokine, IL-22, regulates host immune responses to extracellular
      pathogens. Whether IL-22 plays a role in viral infection, however, is poorly
      understood. We report here that Il22(-/-) mice were more resistant to lethal West
      Nile virus (WNV) encephalitis, but had similar viral loads in the periphery
      compared to wild type (WT) mice. Viral loads, leukocyte infiltrates,
      proinflammatory cytokines and apoptotic cells in the central nervous system (CNS)
      of Il22(-/-) mice were also strikingly reduced. Further examination showed that
      Cxcr2, a chemokine receptor that plays a non-redundant role in mediating
      neutrophil migration, was significantly reduced in Il22(-/-) compared to WT
      leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22(-/-)
      brains than wild type mice. Correspondingly, neutrophil migration from the blood
      into the brain was attenuated following lethal WNV infection of Il22(-/-) mice.
      Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis
      likely by promoting WNV neuroinvasion.

PMID- 22952909
TI  - Adenosine deaminase polymorphism affects sleep EEG spectral power in a large
      epidemiological sample.
AB  - Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect
      both sleep need and intensity, which are implied in homeostatic regulation.
      Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide
      polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with
      deeper and more efficient sleep. The present study verified the association
      between the ADA G22A polymorphism and changes in sleep EEG spectral power (from
      C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study
      (EPISONO) sample from Sao Paulo, Brazil. Eight-hundred individuals were subjected
      to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the
      EEG was carried out in all individuals using fast Fourier transformation of the
      signals from each EEG electrode. The genotype groups were compared in the whole
      sample and in a subsample of 120 individuals matched according to ADA genotype
      for age, gender, body mass index, caffeine intake status, presence of sleep
      disturbance, and sleep-disturbing medication. When compared with homozygous GG
      genotype carriers, A allele carriers showed higher delta spectral power in Stage
      1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and
      REM sleep. These changes were seen both in the whole sample and in the matched
      subset. The higher EEG spectral power indicates that the sleep of individuals
      carrying the A allele may be more intense. Therefore, this polymorphism may be an
      important source of variation in sleep homeostasis in humans, through modulation
      of specific components of the sleep EEG.

PMID- 22952910
TI  - Spatial variability of benthic-pelagic coupling in an estuary ecosystem:
      consequences for microphytobenthos resuspension phenomenon.
AB  - The high degree of physical factors in intertidal estuarine ecosystem increases
      material processing between benthic and pelagic compartments. In these
      ecosystems, microphytobenthos resuspension is a major phenomenon since its
      contribution to higher trophic levels can be highly significant. Understanding
      the sediment and associated microphytobenthos resuspension and its fate in the
      water column is indispensable for measuring the food available to benthic and
      pelagic food webs. To identify and hierarchize the physical/biological factors
      potentially involved in MPB resuspension, the entire intertidal area and
      surrounding water column of an estuarine ecosystem, the Bay des Veys, was sampled
      during ebb tide. A wide range of physical parameters (hydrodynamic regime, grain
      size of the sediment, and suspended matter) and biological parameters (flora and
      fauna assemblages, chlorophyll) were analyzed to characterize benthic-pelagic
      coupling at the bay scale. Samples were collected in two contrasted periods,
      spring and late summer, to assess the impact of forcing variables on benthic
      pelagic coupling. A mapping approach using kriging interpolation enabled us to
      overlay benthic and pelagic maps of physical and biological variables, for both
      hydrological conditions and trophic indicators. Pelagic Chl a concentration was
      the best predictor explaining the suspension-feeders spatial distribution. Our
      results also suggest a perennial spatio-temporal structure of both benthic and
      pelagic compartments in the ecosystem, at least when the system is not imposed to
      intense wind, with MPB distribution controlled by both grain size and bathymetry.
      The benthic component appeared to control the pelagic one via resuspension
      phenomena at the scale of the bay. Co-inertia analysis showed closer benthic
      pelagic coupling between the variables in spring. The higher MPB biomass observed
      in summer suggests a higher contribution to filter-feeders diets, indicating a
      higher resuspension effect in summer than in spring, in turn suggesting an
      important role of macrofauna bioturbation and filter feeding (Cerastoderma
      edule).

PMID- 22952911
TI  - Pharmacodynamics of antimicrobials against Mycoplasma mycoides mycoides small
      colony, the causative agent of contagious bovine pleuropneumonia.
AB  - BACKGROUND: Mycoplasma mycoides subspecies mycoides Small Colony (MmmSC) is the
      causative agent of Contagious Bovine Pleuropneumonia (CBPP), a disease of
      substantial economic importance in sub-Saharan Africa. Failure of vaccination to
      curtail spread of this disease has led to calls for evaluation of the role of
      antimicrobials in CBPP control. Three major classes of antimicrobial are
      effective against mycoplasmas, namely tetracyclines, fluoroquinolones and
      macrolides. Therefore, the objectives of this study were to determine the
      effector kinetics of oxytetracycline, danofloxacin and tulathromycin against two
      MmmSC field strains in artificial medium and adult bovine serum. METHODS: Minimum
      inhibitory concentrations (MIC) were determined for oxytetracycline, danofloxacin
      and tulathromycin against MmmSC strains B237 and Tan8 using a macrodilution
      technique, and time-kill curves were constructed for various multiples of the MIC
      over a 24 hour period in artificial medium and serum. Data were fitted to sigmoid
      E(max) models to obtain 24 hour-area under curve/MIC ratios for mycoplasmastasis
      and, where appropriate, for mycoplasmacidal activity and virtual mycoplasmal
      elimination. RESULTS: Minimum inhibitory concentrations against B237 were 20-fold
      higher, 2-fold higher and approximately 330-fold lower in serum than in
      artificial medium for oxytetracycline, danofloxacin and tulathromycin,
      respectively. Such differences were mirrored in experiments using Tan8.
      Oxytetracycline was mycoplasmastatic against both strains in both matrices.
      Danofloxacin elicited mycoplasmacidal activity against B237 and virtual
      elimination of Tan8; similar maximum antimycoplasmal effects were observed in
      artificial medium and serum. Tulathromycin effected virtual elimination of B237
      but was mycoplasmastatic against Tan8 in artificial medium. However, this drug
      was mycoplasmastatic against both strains in the more physiologically relevant
      matrix of serum. CONCLUSIONS: Oxytetracycline, danofloxacin and tulathromycin are
      all suitable candidates for further investigation as potential treatments for
      CBPP. This study also highlights the importance of testing drug activity in
      biological matrices as well as artificial media.

PMID- 22952912
TI  - Using FLIM-FRET to measure conformational changes of transglutaminase type 2 in
      live cells.
AB  - Transglutaminase type 2 (TG2) is a ubiquitously expressed member of the
      transglutaminase family, capable of mediating a transamidation reaction between a
      variety of protein substrates. TG2 also has a unique role as a G-protein with
      GTPase activity. In response to GDP/GTP binding and increases in intracellular
      calcium levels, TG2 can undergo a large conformational change that reciprocally
      modulates the enzymatic activities of TG2. We have generated a TG2 biosensor that
      allows for quantitative assessment of TG2 conformational changes in live cells
      using Forster resonance energy transfer (FRET), as measured by fluorescence
      lifetime imaging microscopy (FLIM). Quantifying FRET efficiency with this
      biosensor provides a robust assay to quickly measure the effects of cell stress,
      changes in calcium levels, point mutations and chemical inhibitors on the
      conformation and localization of TG2 in living cells. The TG2 FRET biosensor was
      validated using established TG2 conformational point mutants, as well as cell
      stress events known to elevate intracellular calcium levels. We demonstrate in
      live cells that inhibitors of TG2 transamidation activity can differentially
      influence the conformation of the enzyme. The irreversible inhibitor of TG2, NC9,
      forces the enzyme into an open conformation, whereas the reversible inhibitor
      CP4d traps TG2 in the closed conformation. Thus, this biosensor provides new
      mechanistic insights into the action of two TG2 inhibitors and defines two new
      classes based on ability to alter TG2 conformation in addition to inhibiting
      transamidation activity. Future applications of this biosensor could be to
      discover small molecules that specifically alter TG2 conformation to affect
      GDP/GTP or calcium binding.

PMID- 22952913
TI  - Development of a novel molecular sensor for imaging estrogen receptor-coactivator
      protein-protein interactions.
AB  - Anti-estrogens, in particular tissue selective anti-estrogens, have been the
      bedrock of adjuvant therapy for patients with estrogen receptor alpha (ERalpha)
      positive breast cancer. Though current therapies have greatly enhanced patient
      prognosis, there continues to be an impetus for the development of improved anti
      estrogens. ERalpha is a nuclear receptor transcription factor which activates
      gene expression through the recruitment of transcriptional coactivator proteins.
      The SRC family of coactivators, which includes AIB1, has been shown to be of
      particular importance for ERalpha mediated transcription. ERalpha-AIB1
      interactions are indicative of gene expression and are inhibited by anti-estrogen
      treatment. We have exploited the interaction between ERalpha and AIB1 as a novel
      method for imaging ERalpha activity using a split luciferase molecular sensor. By
      producing a range of ERalpha ligand binding domain (ER-LBD) and AIB1 nuclear
      receptor interacting domain (AIB-RID) N- and C-terminal firefly luciferase
      fragment fusion proteins, constructs which exhibited more than a 10-fold increase
      in luciferase activity with E2 stimulation were identified. The specificity of
      the E2-stimulated luciferase activity to ERalpha-AIB1 interaction was validated
      through Y537S and L539/540A ER-LBD fusion protein mutants. The primed nature of
      the split luciferase assay allowed changes in ERalpha activity, with respect to
      the protein-protein interactions preceding transcription, to be assessed soon
      after drug treatment. The novel assay split luciferase detailed in this report
      enabled modulation of ERalpha activity to be sensitively imaged in vitro and in
      living subjects and potentially holds much promise for imaging the efficacy of
      novel ERalpha specific therapies.

PMID- 22952914
TI  - Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB
      receptors.
AB  - In neuronal cells the intracellular trafficking machinery controls the
      availability of neurotransmitter receptors at the plasma membrane, which is a
      critical determinant of synaptic strength. Metabotropic gamma amino-butyric acid
      (GABA) type B receptors (GABA(B)Rs) are neurotransmitter receptors that modulate
      synaptic transmission by mediating the slow and prolonged responses to GABA.
      GABA(B)Rs are obligatory heteromers constituted by two subunits, GABA(B)R1 and
      GABA(B)R2. GABA(B)R1a and GABA(B)R1b are the most abundant subunit variants.
      GABA(B)R1b is located in the somatodendritic domain whereas GABA(B)R1a is
      additionally targeted to the axon. Sushi domains located at the N-terminus of
      GABA(B)R1a constitute the only difference between both variants and are necessary
      and sufficient for axonal targeting. The precise targeting machinery and the
      organelles involved in sorting and transport have not been described. Here we
      demonstrate that GABA(B)Rs require the Golgi apparatus for plasma membrane
      delivery but that axonal sorting and targeting of GABA(B)R1a operate in a pre
      Golgi compartment. In the axon GABA(B)R1a subunits are enriched in the
      endoplasmic reticulum (ER), and their dynamic behavior and colocalization with
      other secretory organelles like the ER-to-Golgi intermediate compartment (ERGIC)
      suggest that they employ a local secretory route. The transport of axonal
      GABA(B)R1a is microtubule-dependent and kinesin-1, a molecular motor of the
      kinesin family, determines axonal localization. Considering that progression of
      GABA(B)Rs through the secretory pathway is regulated by an ER retention motif our
      data contribute to understand the role of the axonal ER in non-canonical sorting
      and targeting of neurotransmitter receptors.

PMID- 22952915
TI  - Secondhand smoke exposure causes bronchial hyperreactivity via transcriptionally
      upregulated endothelin and 5-hydroxytryptamine 2A receptors.
AB  - BACKGROUND: Cigarette smoke exposure is strongly associated with airway
      hyperreactivity (AHR) which is the main characteristic seen in asthma. The
      intracellular MAPK signaling pathways are suggested to be associated with the
      airway damage to the AHR. In the present study, we hypothesize that secondhand
      cigarette smoke (SHS) exposure upregulates the bronchial contractile receptors
      via activation of the Raf/ERK/MAPK pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats
      were exposed to SHS for 3 h daily for up to 8 weeks. The receptor agonists
      induced bronchial contractile reactivity was analyzed with a sensitive myograph
      system. The mRNA transcription and protein translation of the target receptors
      and the kinases in Raf/ERK/MAPK pathway were investigated by real-time PCR,
      Western blotting and immunofluorescence, respectively. Compared with exposure to
      fresh air, SHS induced enhanced bronchial contractile responses mediated by the 5
      hydroxytryptamine 2A (5-HT(2A)) receptors as well as the endothelin type B
      (ET(B)) and type A (ET(A)) receptors. The response curves were shifted toward the
      left with an increased maximal contraction (E(max)) demonstrating that SHS
      induced AHR. Additionally, the mRNA and protein levels of the 5-HT(2A), ET(B) and
      ET(A) receptors were increased. Furthermore, SHS exposure increased the
      phosphorylation of Raf-1 and ERK1/2, but it did not alter p38 or JNK. A Raf-1
      inhibitor (GW5074) suppressed the SHS-induced increase in the expression of 5
      HT(2A) and ET(A) receptors and the receptor-mediated AHR.
      CONCLUSIONS/SIGNIFICANCE: Our findings show that SHS exposure induces
      transcriptional upregulation of the 5-HT(2A), ET(B) and ET(A) receptors in rat
      bronchial smooth muscle cells, which mediates AHR. The Raf/ERK/MAPK pathway is
      involved in SHS-associated receptor upregulation and AHR.

PMID- 22952916
TI  - Analysis of the role of Igf2 in adrenal tumour development in transgenic mouse
      models.
AB  - Adrenal cortical carcinomas (ACC) are rare but aggressive tumours associated with
      poor prognosis. The two most frequent alterations in ACC in patients are
      overexpression of the growth factor IGF2 and constitutive activation of Wnt/beta
      catenin signalling. Using a transgenic mouse model, we have previously shown that
      constitutive active beta-catenin is a bona fide adrenal oncogene. However,
      although all these mice developed benign adrenal hyperplasia, malignant
      progression was infrequent, suggesting that secondary genetic events were
      required for aggressive tumour development. In the present paper, we have tested
      IGF2 oncogenic properties by developing two distinct transgenic mouse models of
      Igf2 overexpression in the adrenal cortex. Our analysis shows that despite
      overexpression levels ranging from 7 (basal) to 87 (ACTH-induced) fold, Igf2 has
      no tumour initiating potential in the adrenal cortex. However, it induces
      aberrant accumulation of Gli1 and Pod1-positive progenitor cells, in a hedgehog
      independent manner. We have also tested the hypothesis that Igf2 may cooperate
      with Wnt signalling by mating Igf2 overexpressing lines with mice that express
      constitutive active beta-catenin in the adrenal cortex. We show that the
      combination of both alterations has no effect on tumour phenotype at stages when
      beta-catenin-induced tumours are benign. However, there is a mild promoting
      effect at later stages, characterised by increased Weiss score and proliferation.
      Formation of malignant tumours is nonetheless a rare event, even when Igf2
      expression is further increased by ACTH treatment. Altogether these experiments
      suggest that the growth factor IGF2 is a mild contributor to malignant
      adrenocortical tumourigenesis.

PMID- 22952917
TI  - Sperm cells induce distinct cytokine response in peripheral mononuclear cells
      from infertile women with serum anti-sperm antibodies.
AB  - BACKGROUND AND AIMS: Anti-sperm antibodies in can markedly reduce the likelihood
      of natural conception. The etiology of this anti-sperm immunity in human females
      is unknown. We compared the cytokine response of peripheral blood mononuclear
      cells (PBMCs) from infertile patients with or without anti-sperm antibodies (ASA)
      and fertile women. METHODOLOGY/PRINCIPAL FINDINGS: We cultivated the PBMCs
      together with sperm antigens (whole cells or cell lysate), and screened the
      supernatants for 40 cytokines by antibody array. When stimulated with whole sperm
      cells, the PBMCs from patients with ASA produce less IL-3, IL-11, IL-13, ICAM-1,
      GCSF and more IL-2, IL-4 and IL-12p70 as compared to healthy women. PBMCs from
      patients with ASA produce typically less IL-13, IL-7, IL-17 and MIG, and more MIP
      1beta and IL-8, as compared to PBMCs from patients without ASA. In response to
      sperm cell lysate, PBMCs from infertile women without ASA respond initially by
      increase in production of growth factors (GCSF, GM-CSF and PDGF-BB) followed by
      increase in chemokines (e.g. IL-8, MCP-1 and MIP-1beta). CONCLUSIONS: Cellular
      immune responses to sperm antigens, measured by production of cytokines, differ
      among infertile women with ASA, infertile women without ASA and healthy women.
      This difference could play an important role in the initial steps of the
      infertility pathogenesis.

PMID- 22952918
TI  - Adaptive ridge regression for rare variant detection.
AB  - It is widely believed that both common and rare variants contribute to the risks
      of common diseases or complex traits and the cumulative effects of multiple rare
      variants can explain a significant proportion of trait variances. Advances in
      high-throughput DNA sequencing technologies allow us to genotype rare causal
      variants and investigate the effects of such rare variants on complex traits. We
      developed an adaptive ridge regression method to analyze the collective effects
      of multiple variants in the same gene or the same functional unit. Our model
      focuses on continuous trait and incorporates covariate factors to remove
      potential confounding effects. The proposed method estimates and tests multiple
      rare variants collectively but does not depend on the assumption of same
      direction of each rare variant effect. Compared with the Bayesian hierarchical
      generalized linear model approach, the state-of-the-art method of rare variant
      detection, the proposed new method is easy to implement, yet it has higher
      statistical power. Application of the new method is demonstrated using the well
      known data from the Dallas Heart Study.

PMID- 22952919
TI  - Distinct and competitive regulatory patterns of tumor suppressor genes and
      oncogenes in ovarian cancer.
AB  - BACKGROUND: So far, investigators have found numerous tumor suppressor genes
      (TSGs) and oncogenes (OCGs) that control cell proliferation and apoptosis during
      cancer development. Furthermore, TSGs and OCGs may act as modulators of
      transcription factors (TFs) to influence gene regulation. A comprehensive
      investigation of TSGs, OCGs, TFs, and their joint target genes at the network
      level may provide a deeper understanding of the post-translational modulation of
      TSGs and OCGs to TF gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we developed a novel computational framework for identifying target genes
      of TSGs and OCGs using TFs as bridges through the integration of protein-protein
      interactions and gene expression data. We applied this pipeline to ovarian cancer
      and constructed a three-layer regulatory network. In the network, the top layer
      was comprised of modulators (TSGs and OCGs), the middle layer included TFs, and
      the bottom layer contained target genes. Based on regulatory relationships in the
      network, we compiled TSG and OCG profiles and performed clustering analyses.
      Interestingly, we found TSGs and OCGs formed two distinct branches. The genes in
      the TSG branch were significantly enriched in DNA damage and repair, regulating
      macromolecule metabolism, cell cycle and apoptosis, while the genes in the OCG
      branch were significantly enriched in the ErbB signaling pathway. Remarkably,
      their specific targets showed a reversed functional enrichment in terms of
      apoptosis and the ErbB signaling pathway: the target genes regulated by OCGs only
      were enriched in anti-apoptosis and the target genes regulated by TSGs only were
      enriched in the ErbB signaling pathway. CONCLUSIONS/SIGNIFICANCE: This study
      provides the first comprehensive investigation of the interplay of TSGs and OCGs
      in a regulatory network modulated by TFs. Our application in ovarian cancer
      revealed distinct regulatory patterns of TSGs and OCGs, suggesting a competitive
      regulatory mechanism acting upon apoptosis and the ErbB signaling pathway through
      their specific target genes.

PMID- 22952920
TI  - Improper tagging of the non-essential small capsid protein VP26 impairs nuclear
      capsid egress of herpes simplex virus.
AB  - To analyze the subcellular trafficking of herpesvirus capsids, the small capsid
      protein has been labeled with different fluorescent proteins. Here, we analyzed
      the infectivity of several HSV1(17(+)) strains in which the N-terminal region of
      the non-essential small capsid protein VP26 had been tagged at different
      positions. While some variants replicated with similar kinetics as their parental
      wild type strain, others were not infectious at all. Improper tagging resulted in
      the aggregation of VP26 in the nucleus, prevented efficient nuclear egress of
      viral capsids, and thus virion formation. Correlative fluorescence and electron
      microscopy showed that these aggregates had sequestered several other viral
      proteins, but often did not contain viral capsids. The propensity for aggregate
      formation was influenced by the type of the fluorescent protein domain, the
      position of the inserted tag, the cell type, and the progression of infection.
      Among the tags that we have tested, mRFPVP26 had the lowest tendency to induce
      nuclear aggregates, and showed the least reduction in replication when compared
      to wild type. Our data suggest that bona fide monomeric fluorescent protein tags
      have less impact on proper assembly of HSV1 capsids and nuclear capsid egress
      than tags that tend to dimerize. Small chemical compounds capable of inducing
      aggregate formation of VP26 may lead to new antiviral drugs against HSV
      infections.

PMID- 22952921
TI  - TRP, TRPL and cacophony channels mediate Ca2+ influx and exocytosis in
      photoreceptors axons in Drosophila.
AB  - In Drosophila photoreceptors Ca(2+)-permeable channels TRP and TRPL are the
      targets of phototransduction, occurring in photosensitive microvilli and mediated
      by a phospholipase C (PLC) pathway. Using a novel Drosophila brain slice
      preparation, we studied the distribution and physiological properties of TRP and
      TRPL in the lamina of the visual system. Immunohistochemical images revealed
      considerable expression in photoreceptors axons at the lamina. Other
      phototransduction proteins are also present, mainly PLC and protein kinase C,
      while rhodopsin is absent. The voltage-dependent Ca(2+) channel cacophony is also
      present there. Measurements in the lamina with the Ca(2+) fluorescent protein G
      CaMP ectopically expressed in photoreceptors, revealed depolarization-induced
      Ca(2+) increments mediated by cacophony. Additional Ca(2+) influx depends on TRP
      and TRPL, apparently functioning as store-operated channels. Single synaptic
      boutons resolved in the lamina by FM4-64 fluorescence revealed that vesicle
      exocytosis depends on cacophony, TRP and TRPL. In the PLC mutant norpA bouton
      labeling was also impaired, implicating an additional modulation by this enzyme.
      Internal Ca(2+) also contributes to exocytosis, since this process was reduced
      after Ca(2+)-store depletion. Therefore, several Ca(2+) pathways participate in
      photoreceptor neurotransmitter release: one is activated by depolarization and
      involves cacophony; this is complemented by internal Ca(2+) release and the
      activation of TRP and TRPL coupled to Ca(2+) depletion of internal reservoirs.
      PLC may regulate the last two processes. TRP and TRPL would participate in two
      different functions in distant cellular regions, where they are opened by
      different mechanisms. This work sheds new light on the mechanism of
      neurotransmitter release in tonic synapses of non-spiking neurons.

PMID- 22952922
TI  - Phylogenetic evidence that two distinct Trichuris genotypes infect both humans
      and non-human primates.
AB  - Although there has been extensive debate about whether Trichuris suis and
      Trichuris trichiura are separate species, only one species of the whipworm T.
      trichiura has been considered to infect humans and non-human primates. In order
      to investigate potential cross infection of Trichuris sp. between baboons and
      humans in the Cape Peninsula, South Africa, we sequenced the ITS1-5.8S-ITS2
      region of adult Trichuris sp. worms isolated from five baboons from three
      different troops, namely the Cape Peninsula troop, Groot Olifantsbos troop and Da
      Gama Park troop. This region was also sequenced from T. trichiura isolated from a
      human patient from central Africa (Cameroon) for comparison. By combining this
      dataset with Genbank records for Trichuris isolated from other humans, non-human
      primates and pigs from several different countries in Europe, Asia, and Africa,
      we confirmed the identification of two distinct Trichuris genotypes that infect
      primates. Trichuris sp. isolated from the Peninsula baboons fell into two
      distinct clades that were found to also infect human patients from Cameroon,
      Uganda and Jamaica (named the CP-GOB clade) and China, Thailand, the Czech
      Republic, and Uganda (named the DG clade), respectively. The divergence of these
      Trichuris clades is ancient and precedes the diversification of T. suis which
      clustered closely to the CP-GOB clade. The identification of two distinct
      Trichuris genotypes infecting both humans and non-human primates is important for
      the ongoing treatment of Trichuris which is estimated to infect 600 million
      people worldwide. Currently baboons in the Cape Peninsula, which visit urban
      areas, provide a constant risk of infection to local communities. A reduction in
      spatial overlap between humans and baboons is thus an important measure to reduce
      both cross-transmission and zoonoses of helminthes in Southern Africa.

PMID- 22952923
TI  - Glutamate excitoxicity is the key molecular mechanism which is influenced by body
      temperature during the acute phase of brain stroke.
AB  - Glutamate excitotoxicity, metabolic rate and inflammatory response have been
      associated to the deleterious effects of temperature during the acute phase of
      stroke. So far, the association of temperature with these mechanisms has been
      studied individually. However, the simultaneous study of the influence of
      temperature on these mechanisms is necessary to clarify their contributions to
      temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance
      Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and
      metabolic rate in the brain in animal models of ischemia. The immune response to
      ischemia was measured through molecular serum markers in peripheral blood. We
      submitted groups of animals to different experimental conditions (hypothermia at
      33 degrees C, normothermia at 37 degrees C and hyperthermia at 39 degrees C), and
      combined these conditions with pharmacological modulation of glutamate levels in
      the brain through systemic injections of glutamate and oxaloacetate. We show that
      pharmacological modulation of glutamate levels can neutralize the deleterious
      effects of hyperthermia and the beneficial effects of hypothermia, however the
      analysis of the inflammatory response and metabolic rate, demonstrated that their
      effects on ischemic damage are less critical than glutamate excitotoxity. We
      conclude that glutamate excitotoxicity is the key molecular mechanism which is
      influenced by body temperature during the acute phase of brain stroke.

PMID- 22952924
TI  - Calcineurin is required for pseudohyphal growth, virulence, and drug resistance
      in Candida lusitaniae.
AB  - Candida lusitaniae is an emerging fungal pathogen that infects immunocompromised
      patients including HIV/AIDS, cancer, and neonatal pediatric patients. Though less
      prevalent than other Candida species, C. lusitaniae is unique in its ability to
      develop resistance to amphotericin B. We investigated the role of the calcium
      activated protein phosphatase calcineurin in several virulence attributes of C.
      lusitaniae including pseudohyphal growth, serum survival, and growth at 37
      degrees C. We found that calcineurin and Crz1, a C. albicans Crz1 homolog acting
      as a downstream target of calcineurin, are required for C. lusitaniae
      pseudohyphal growth, a process for which the underlying mechanism remains largely
      unknown in C. lusitaniae but hyphal growth is fundamental to C. albicans
      virulence. We demonstrate that calcineurin is required for cell wall integrity,
      ER stress response, optimal growth in serum, virulence in a murine systemic
      infection model, and antifungal drug tolerance in C. lusitaniae. To further
      examine the potential of targeting the calcineurin signaling cascade for
      antifungal drug development, we examined the activity of a calcineurin inhibitor
      FK506 in combination with caspofungin against echinocandin resistant C.
      lusitaniae clinical isolates. Broth microdilution and drug disk diffusion assays
      demonstrate that FK506 has synergistic fungicidal activity with caspofungin
      against echinocandin resistant isolates. Our findings reveal that pseudohyphal
      growth is controlled by the calcineurin signaling cascade, and highlight the
      potential use of calcineurin inhibitors and caspofungin for emerging drug
      resistant C. lusitaniae infections.

PMID- 22952925
TI  - New insights on the sialidase protein family revealed by a phylogenetic analysis
      in metazoa.
AB  - Sialidases are glycohydrolytic enzymes present from virus to mammals that remove
      sialic acid from oligosaccharide chains. Four different sialidase forms are known
      in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane
      associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and
      are involved in several cellular processes and pathological conditions. Molecular
      defects in NEU1 are responsible for sialidosis, an inherited disease
      characterized by lysosomal storage disorder and neurodegeneration. The studies on
      the biology of sialic acids and sialyltransferases, the anabolic counterparts of
      sialidases, have revealed a complex picture with more than 50 sialic acid
      variants selectively present in the different branches of the tree of life. The
      gain/loss of specific sialoconjugates have been proposed as key events in the
      evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen
      interactions. To date, less attention has been paid to the evolution of
      sialidases. Thus we have conducted a survey on the state of the sialidase family
      in metazoan. Using an in silico approach, we identified and characterized
      sialidase orthologs from 21 different organisms distributed among the
      evolutionary tree: Metazoa relative (Monosiga brevicollis), early Deuterostomia,
      precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles,
      avians and early and recent mammals). We were able to reconstruct the evolution
      of the sialidase protein family from the ancestral sialidase NEU1 and identify a
      new form of the enzyme, NEU5, representing an intermediate step in the evolution
      leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the
      mechanisms that shaped the substrate specificity and other peculiar properties of
      the modern mammalian sialidases. Moreover, we further confirm findings on the
      catalytic residues and identified enzyme loop portions that behave as rapidly
      diverging regions and may be involved in the evolution of specific properties of
      sialidases.

PMID- 22952926
TI  - Investigating structural brain changes of dehydration using voxel-based
      morphometry.
AB  - Dehydration can affect the volume of brain structures, which might imply a
      confound in volumetric and morphometric studies of normal or diseased brain. Six
      young, healthy volunteers were repeatedly investigated using three-dimensional
      T(1)-weighted magnetic resonance imaging during states of normal hydration,
      hyperhydration, and dehydration to assess volume changes in gray matter (GM),
      white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed
      using voxel-based morphometry (VBM), a widely used voxel-wise statistical
      analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and
      SIENAr a longitudinal brain-change detection algorithm. A significant decrease of
      GM and WM volume associated with dehydration was found in various brain regions,
      most prominently, in temporal and sub-gyral parietal areas, in the left inferior
      orbito-frontal region, and in the extra-nuclear region. Moreover, we found
      consistent increases in CSF, that is, an expansion of the ventricular system
      affecting both lateral ventricles, the third, and the fourth ventricle. Similar
      degrees of shrinkage in WM volume and increase of the ventricular system have
      been reported in studies of mild cognitive impairment or Alzheimer's disease
      during disease progression. Based on these findings, a potential confound in GM
      and WM or ventricular volume studies due to the subjects' hydration state cannot
      be excluded and should be appropriately addressed in morphometric studies of the
      brain.

PMID- 22952927
TI  - Effective non-viral delivery of siRNA to acute myeloid leukemia cells with lipid
      substituted polyethylenimines.
AB  - Use of small interfering RNA (siRNA) is a promising approach for AML treatment as
      the siRNA molecule can be designed to specifically target proteins that
      contribute to aberrant cell proliferation in this disease. However, a clinical
      relevant means of delivering siRNA molecules must be developed, as the cellular
      delivery of siRNA is problematic. Here, we report amphiphilic carriers combining
      a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to
      facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of
      siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~ 0.5 and
      led to siRNA/polymer complexes of ~ 100 nm size. While the native PEI2 did not
      display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification
      on PEI2 slightly increased the cytotoxicity, which was consistent with increased
      interaction of polymers with cell membranes. Cellular delivery of siRNA was
      dependent on the nature of lipid substituent and the extent of lipid
      substitution, and varied among the three AML cell lines used. Linoleic acid
      substituted polymers performed best among the prepared polymers and gave a siRNA
      delivery equivalent to better performing commercial reagents. Using THP-1 cells
      and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the
      chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without
      adversely affecting subsequent cell growth. We conclude that lipid-substituted
      PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be
      employed in molecular therapy of leukemia.

PMID- 22952929
TI  - Development of the Fc-III tagged protein expression system for protein
      purification and detection.
AB  - In the present work, we developed the Fc-III tagged protein expression system for
      protein purification and detection. The Fc-III sequence encodes for a 13 residue
      peptide and this peptide is cyclized by disulfide bond formation when the fusion
      protein is expressed. The Fc-III-fusion proteins selectively bind to
      immunoglobulin Fc domains (IgG-Fc) expressed from E. coli. We showed the
      efficient purification of Fc-III tagged proteins by immobilized non-native IgG-Fc
      and the detection of the cellular locations of fusion proteins by fluorescent
      conjugated IgG-Fc. Our results prove that Fc-III tagged protein expression system
      is a simple and efficient tool for protein purification and detection and is a
      useful addition to the biochemistry and proteomics toolbox.

PMID- 22952928
TI  - Estimated glomerular filtration rate is a poor predictor of the concentration of
      middle molecular weight uremic solutes in chronic kidney disease.
AB  - BACKGROUND: Uremic solute concentration increases as Glomerular Filtration Rate
      (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR)
      and the concentrations of several small water-soluble and protein-bound uremic
      solutes (MW<500 Da). Since also middle molecular weight proteins have been
      associated with mortality and cardiovascular damage in Chronic Kidney Disease
      (CKD), we investigated the association between several eGFR formulae and the
      concentration of Low Molecular Weight Proteins (LMWP) (MW>500 Da). MATERIALS AND
      METHODS: In 95 CKD-patients (CKD-stage 2-5 not on dialysis), associations between
      different eGFR-formulae (creatinine, Cystatin C-based or both) and the natural
      logarithm of the concentration of several LMWP's were analyzed: i.e. parathyroid
      hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), leptin, retinol binding protein (RbP), immunoglobin light
      chains kappa and lambda (Ig-kappa and Ig-lambda), beta-2-microglobulin
      (beta(2)M), myoglobin and fibroblast growth factor-23 (FGF-23)). RESULTS: The
      regression coefficients (R(2)) between eGFR, based on the CKD-EPI-Crea-CystC
      formula as reference, and the examined LMWP's could be divided into three groups.
      Most of the LMWP's associated weakly (R(2) <0.2) (FGF-23, leptin, IL-6, TNF
      alpha, Ig-kappa, Ig-lambda) or intermediately (R(2) 0.2-0.7) (RbP, myoglobin,
      PTH). Only beta(2)M and CystC showed a strong association (R(2) >0.7). Almost
      identical R(2)-values were found per LMWP for all eGFR-formulae, with exception
      of CystC and beta(2)M which showed weaker associations with creatinine-based than
      with CystC-based eGFR. CONCLUSION: The association between eGFR and the
      concentration of several LMWP's is inconsistent, with in general low R(2)-values.
      Thus, the use of eGFR to evaluate kidney function does not reflect the
      concentration of several LMWP's with proven toxic impact in CKD.

PMID- 22952930
TI  - Advantages and limitations of different p62-based assays for estimating
      autophagic activity in Drosophila.
AB  - Levels of the selective autophagy substrate p62 have been established in recent
      years as a specific readout for basal autophagic activity. Here we compared
      different experimental approaches for using this assay in Drosophila larvae.
      Similar to the more commonly used western blots, quantifying p62 dots in
      immunostained fat body cells of L3 stage larvae detected a strong accumulation of
      endogenous p62 aggregates in null mutants for Atg genes and S6K. Importantly,
      genes whose mutation or silencing results in early stage lethality can only be
      analyzed by microscopy using clonal analysis. The loss of numerous general
      housekeeping genes show a phenotype in large-scale screens including autophagy,
      and the p62 assay was potentially suitable for distinguishing bona fide autophagy
      regulators from silencing of a DNA polymerase subunit or a ribosomal gene that
      likely has a non-specific effect on autophagy. p62 accumulation upon RNAi
      silencing of known autophagy regulators was dependent on the duration of the
      knockdown effect, unlike in the case of starvation-induced autophagy. The
      endogenous p62 assay was more sensitive than a constitutively overexpressed p62
      GFP reporter, which showed self-aggregation and large-scale accumulation even in
      control cells. We recommend western blots for following the conversion of
      overexpressed p62-GFP reporters to estimate autophagic activity if sample
      collection from mutant larvae or adults is possible. In addition, we also showed
      that overexpressed p62 or Atg8 reporters can strongly influence the phenotypes of
      each other, potentially giving rise to false or contradicting results.
      Overexpressed p62 aggregates also incorporated Atg8 reporter molecules that might
      lead to a wrong conclusion of strongly enhanced autophagy, whereas expression of
      an Atg8 reporter transgene rescued the inhibitory effect of a dominant-negative
      Atg4 mutant on basal and starvation-induced autophagy.

PMID- 22952931
TI  - Betaglycan (TbetaRIII) is expressed in the thymus and regulates T cell
      development by protecting thymocytes from apoptosis.
AB  - TGF-beta type III receptor (TbetaRIII) is a coreceptor for TGFbeta family members
      required for high-affinity binding of these ligands to their receptors,
      potentiating their cellular functions. TGF-beta [1]-[3], bone morphogenetic
      proteins (BMP2/4) and inhibins regulate different checkpoints during T cell
      differentiation. Although TbetaRIII is expressed on hematopoietic cells, the role
      of this receptor in the immune system remains elusive. Here, we provide the first
      evidence that TbetaRIII is developmentally expressed during T cell ontogeny, and
      plays a crucial role in thymocyte differentiation. Blocking of endogenous
      TbetaRIII in fetal thymic organ cultures led to a delay in DN-DP transition. In
      addition, in vitro development of TbetaRIII(-/-) thymic lobes also showed a
      significant reduction in absolute thymocyte numbers, which correlated with
      increased thymocyte apoptosis, resembling the phenotype reported in Inhibin alpha
      (-/-) thymic lobes. These data suggest that Inhibins and TbetaRIII may function
      as a molecular pair regulating T cell development.

PMID- 22952932
TI  - Identification of thalidomide-specific transcriptomics and proteomics signatures
      during differentiation of human embryonic stem cells.
AB  - Embryonic development can be partially recapitulated in vitro by differentiating
      human embryonic stem cells (hESCs). Thalidomide is a developmental toxicant in
      vivo and acts in a species-dependent manner. Besides its therapeutic value,
      thalidomide also serves as a prototypical model to study teratogenecity. Although
      many in vivo and in vitro platforms have demonstrated its toxicity, only a few
      test systems accurately reflect human physiology. We used global gene expression
      and proteomics profiling (two dimensional electrophoresis (2DE) coupled with
      Tandem Mass spectrometry) to demonstrate hESC differentiation and thalidomide
      embryotoxicity/teratogenecity with clinically relevant dose(s). Proteome analysis
      showed loss of POU5F1 regulatory proteins PKM2 and RBM14 and an over expression
      of proteins involved in neuronal development (such as PAK2, PAFAH1B2 and
      PAFAH1B3) after 14 days of differentiation. The genomic and proteomic expression
      pattern demonstrated differential expression of limb, heart and embryonic
      development related transcription factors and biological processes. Moreover,
      this study uncovered novel possible mechanisms, such as the inhibition of RANBP1,
      that participate in the nucleocytoplasmic trafficking of proteins and inhibition
      of glutathione transferases (GSTA1, GSTA2), that protect the cell from secondary
      oxidative stress. As a proof of principle, we demonstrated that a combination of
      transcriptomics and proteomics, along with consistent differentiation of hESCs,
      enabled the detection of canonical and novel teratogenic intracellular mechanisms
      of thalidomide.

PMID- 22952933
TI  - New ataxic tottering-6j mouse allele containing a Cacna1a gene mutation.
AB  - Voltage-gated Ca(2+) (Ca(v)) channels control neuronal functions including
      neurotransmitter release and gene expression. The Cacna1a gene encodes the alpha1
      subunit of the pore-forming Ca(v)2.1 channel. Mice with mutations in this gene
      form useful tools for defining channel functions. The recessive ataxic tottering
      6j strain that was generated in the Neuroscience Mutagenesis Facility at The
      Jackson Laboratory has a mutation in the Cacna1a gene. However, the effect of
      this mutation has not been investigated in detail. In this study, mutation
      analysis shows a base substitution (C-to-A) in the consensus splice acceptor
      sequence linked to exon 5, which results in the skipping of exon 5 and the
      splicing of exon 4 directly to exon 6. The effect of this mutation is expected to
      be severe as the expressed alpha1 subunit protein lacks a significant part of the
      S4-S5 linker, S5, and part of S5-S6 linker in domain I. Tottering-6j mice display
      motor dysfunctions in the footprint, rotating rod, and hind-limb extension tests.
      Although cytoarchitecture of the mutant brains appears normal, tyrosine
      hydroxylase was persistently expressed in cerebellar Purkinje cells in the adult
      mutant mice. These results indicate that tottering-6j is a useful model for
      functional studies of the Ca(v)2.1 channel.

PMID- 22952934
TI  - Evaluation of a novel hexavalent humanized anti-IGF-1R antibody and its bivalent
      parental IgG in diverse cancer cell lines.
AB  - A major mechanism of monoclonal antibodies that selectively target the insulin
      like growth factor type 1 receptor (IGF-1R) to inhibit tumor growth is by
      downregulating the receptor, regardless whether they are capable (antagonistic)
      or incapable (agonistic) of blocking the binding of cognate ligands. We have
      developed and characterized a novel agonistic anti-IGF-1R humanized antibody,
      hR1, and used the Dock-and-Lock (DNL) method to construct Hex-hR1, the first
      multivalent antibody comprising 6 functional Fabs of hR1, with the aim of
      enhancing potency of hR1. Based on cross-blocking experiments, hR1 recognizes a
      region of cysteine-rich domain on the alpha-subunit, different from the epitopes
      mapped for existing anti-IGF-1R antibodies, yet hR1 is similar to other anti-IGF
      1R antibodies in downregulating IGF-1R and inhibiting proliferation, colony
      formation, or invasion of selected cancer cell lines in vitro, as well as
      suppressing growth of the RH-30 rhabdomyosarcoma xenograft in nude mice when
      combined with the mTOR inhibitor, rapamycin. Hex-hR1 and hR1 are generally
      comparable in their bioactivities under the in-intro and in-vivo conditions
      investigated. Nevertheless, in selective experiments involving a direct
      comparison of potency, Hex-hR1 demonstrated a stronger effect on inhibiting cell
      proliferation stimulated by IGF-1 and could effectively downregulate IGF-1R at a
      concentration as low as 20 pM.

PMID- 22952935
TI  - Systems genetics of the lateral septal nucleus in mouse: heritability, genetic
      control, and covariation with behavioral and morphological traits.
AB  - The lateral septum has strong efferent projections to hypothalamic and midbrain
      regions, and has been associated with modulation of social behavior, anxiety,
      fear conditioning, memory-related behaviors, and the mesolimbic reward pathways.
      Understanding natural variation of lateral septal anatomy and function, as well
      as its genetic modulation, may provide important insights into individual
      differences in these evolutionarily important functions. Here we address these
      issues by using efficient and unbiased stereological probes to estimate the
      volume of the lateral septum in the BXD line of recombinant inbred mice. Lateral
      septum volume is a highly variable trait, with a 2.5-fold difference among
      animals. We find that this trait covaries with a number of behavioral and
      physiological phenotypes, many of which have already been associated with
      behaviors modulated by the lateral septum, such as spatial learning, anxiety, and
      reward-seeking. Heritability of lateral septal volume is moderate (h(2) = 0.52),
      and much of the heritable variation is caused by a locus on the distal portion of
      chromosome (Chr) 1. Composite interval analysis identified a secondary interval
      on Chr 2 that works additively with the Chr 1 locus to increase lateral septum
      volume. Using bioinformatic resources, we identified plausible candidate genes in
      both intervals that may influence the volume of this key nucleus, as well as
      associated behaviors.

PMID- 22952936
TI  - Diurnal variation of hepatic antioxidant gene expression in mice.
AB  - BACKGROUND: This study was aimed to examine circadian variations of hepatic
      antioxidant components, including the Nrf2- pathway, the glutathione (GSH)
      system, antioxidant enzymes and metallothionein in mouse liver. METHODS AND
      RESULTS: Adult mice were housed in light- and temperature-controlled facilities
      for 2 weeks, and livers were collected every 4 h during the 24 h period. Total
      RNA was isolated, purified, and subjected to real-time RT-PCR analysis. Hepatic
      mRNA levels of Nrf2, Keap1, Nqo1 and Gclc were higher in the light-phase than the
      dark-phase, and were female-predominant. Hepatic GSH presented marked circadian
      fluctuations, along with glutathione S-transferases (GST-alpha1, GST-u, GST-pi)
      and glutathione peroxidase (GPx1). The expressions of GPx1, GST-u and GST-pi mRNA
      were also higher in females. Antioxidant enzymes Cu/Zn superoxide dismutase
      (Sod1), catalase (CAT), cyclooxygenase-2 (Cox-2) and heme oxygenase-1 (Ho-1)
      showed circadian rhythms, with higher expressions of Cox-2 and CAT in females.
      Metallothionein, a small non-enzymatic antioxidant protein, showed dramatic
      circadian variation in males, but higher expression in females. The circadian
      variations of the clock gene Brain and Muscle Arnt-like Protein-1(Bmal1), albumin
      site D-binding protein (Dbp), nuclear receptor Rev-Erbalpha (Nr1d1), period
      protein (Per1 and Per2) and cryptochrome 1(Cry1) were in agreement with the
      literature. Furthermore, acetaminophen hepatotoxicity is more severe when
      administered in the afternoon when hepatic GSH was lowest. CONCLUSIONS: Circadian
      variations and gender differences in transcript levels of antioxidant genes exist
      in mouse liver, which could affect body responses to oxidative stress at
      different times of the day.

PMID- 22952937
TI  - Association between human papillomavirus and human T-lymphotropic virus in
      indigenous women from the Peruvian Amazon.
AB  - BACKGROUND: No association between the Human T-cell lymphotropic virus (HTLV), an
      oncogenic virus that alters host immunity, and the Human Papillomavirus (HPV) has
      previously been reported. Examining the association between these two viruses may
      permit the identification of a population at increased risk for developing
      cervical cancer. METHODS AND FINDINGS: Between July 2010 and February 2011, we
      conducted a cross-sectional study among indigenous Amazonian Peruvian women from
      the Shipibo-Konibo ethnic group, a group with endemic HTLV infection. We
      recruited women between 15 and 39 years of age who were living in the cities of
      Lima and Ucayali. Our objectives were to determine the association between HTLV
      and: (i) HPV infection of any type, and (ii) high-risk HPV type infection.
      Sexually active Shipibo-Konibo women were screened for HTLV-1 and HTLV-2
      infections. All HTLV-1 or -2 positive women, along with two community-matched
      HTLV negative sexually active Shipibo-Konibo controls were later tested for the
      presence of HPV DNA, conventional cytology, and HIV. We screened 1,253 Shipibo
      Konibo women, observing a prevalence of 5.9% (n = 74) for HTLV-1 and 3.8% (n =
      47) for HTLV-2 infections. We enrolled 62 (60.8%) HTLV-1 positive women, 40
      (39.2%) HTLV-2 positive women, and 205 community-matched HTLV negative controls.
      HTLV-1 infection was strongly associated with HPV infection of any type (43.6%
      vs. 29.3%; Prevalence Ratio (PR): 2.10, 95% CI: 1.53-2.87), and with high-risk
      HPV infection (32.3% vs. 22.4%; PR: 1.93, 95% CI: 1.04-3.59). HTLV-2 was not
      significantly associated with either of these HPV infections. CONCLUSIONS: HTLV-1
      infection was associated with HPV infection of any type and with high-risk HPV
      infection. Future longitudinal studies are needed to evaluate the incidence of
      high-risk HPV infection as well as the incidence of cervical neoplasia among HTLV
      1 positive women.

PMID- 22952938
TI  - SHP-1 phosphatase is a critical regulator in preventing natural killer cell self
      killing.
AB  - Balance of signals generated from the engaged activating and inhibitory surface
      receptors regulates mature NK cell activities. The inhibitory receptors signal
      through immunoreceptor tyrosine based inhibitory motifs (ITIM), and recruit
      phosphatases such as SHP-1 to inhibit NK cell activation. To directly examine the
      importance of SHP-1 in regulating activities and cell fate of mature NK cells, we
      used our established lentiviral-based engineering protocol to knock down the SHP
      1 protein expression in primary C57BL/6NCrl cells. Gene silencing of the SHP-1 in
      primary NK cells abrogated the ability of ITIM-containing NK inhibitory receptors
      to suppress the activation signals induced by NK1.1 activating receptors. We
      followed the fates of stably transduced SHP-1 silenced primary NK cells over a
      longer period of time in IL-2 containing cultures. We observed an impaired IL-2
      induced proliferation in the SHP-1 knockdown NK cells. More interestingly, these
      "de-regulated" SHP-1 knockdown NK cells mediated specific self-killing in a real
      time live cell microscopic imaging system we developed to study NK cell
      cytotoxicity in vitro. Selective target recognition of the SHP-1 knockdown NK
      cells revealed also possible involvement of the SHP-1 phosphatase in regulating
      other NK functions in mature NK cells.

PMID- 22952939
TI  - Activity of trifluoperazine against replicating, non-replicating and drug
      resistant M. tuberculosis.
AB  - Trifluoperazine, a known calmodulin antagonist, belongs to a class of
      phenothiazine compounds that have multiple sites of action in mycobacteria
      including lipid synthesis, DNA processes, protein synthesis and respiration. The
      objective of this study is to evaluate the potential of TFP to be used as a lead
      molecule for development of novel TB drugs by showing its efficacy on multiple
      drug resistant (MDR) Mycobacterium tuberculosis (M.tb) and non-replicating
      dormant M.tb. Wild type and MDR M.tb were treated with TFP under different growth
      conditions of stress like low pH, starvation, presence of nitric oxide and in THP
      1 infection model. Perturbation in growth kinetics of bacilli at different
      concentrations of TFP was checked to determine the MIC of TFP for active as well
      as dormant bacilli. Results show that TFP is able to significantly reduce the
      actively replicating as well as non-replicating bacillary load. It has also shown
      inhibitory effect on the growth of MDR M.tb. TFP has shown enhanced activity
      against intracellular bacilli, presumably because phenothiazines are known to get
      accumulated in macrophages. This concentration was, otherwise, found to be non
      toxic to macrophage in vitro. Our results show that TFP has the potential to be
      an effective killer of both actively growing and non-replicating bacilli
      including MDR TB. Further evaluation and in vivo studies with Trifluoperazine can
      finally help us know the feasibility of this compound to be used as either a lead
      compound for development of new TB drugs or as an adjunct in the current TB
      chemotherapy.

PMID- 22952940
TI  - Stronger sexual selection in warmer waters: the case of a sex role reversed
      pipefish.
AB  - In order to answer broader questions about sexual selection, one needs to measure
      selection on a wide array of phenotypic traits, simultaneously through space and
      time. Nevertheless, studies that simultaneously address temporal and spatial
      variation in reproduction are scarce. Here, we aimed to investigate the
      reproductive dynamics of a cold-water pipefish simultaneously through time
      (encompassing variation within each breeding cycle and as individuals grow) and
      space (by contrasting populations experiencing distinct water temperature
      regimes) in order to test hypothesized differences in sexual selection. Even
      though the sampled populations inhabited locations with very different water
      temperature regimes, they exhibited considerable similarities in reproductive
      parameters. The most striking was the existence of a well-defined substructure in
      reproductive activity, where larger individuals reproduce for longer periods,
      which seemed dependent on a high temperature threshold for breeding rather than
      on the low temperatures that vary heavily according to latitude. Furthermore, the
      perceived disparities among populations, such as size at first reproduction,
      female reproductive investment, or degree of sexual size dimorphism, seemed
      dependent on the interplay between seawater temperature and the operational sex
      ratio (OSR). Contrary to our expectations of an enhanced opportunity for sexual
      selection in the north, we found the opposite: higher female reproductive
      investment coupled with increased sexual size dimorphism in warmer waters,
      implying that a prolonged breeding season does not necessarily translate into
      reduced sexual selection pressure. In fact, if the limited sex has the ability to
      reproduce either continuously or recurrently during the entire breeding season,
      an increased opportunity for sexual selection might arise from the need to
      compete for available partners under strongly biased OSRs across protracted
      breeding seasons. A more general discussion on the effects of climate change in
      the pressure of sexual selection is also presented.

PMID- 22952941
TI  - The PICALM protein plays a key role in iron homeostasis and cell proliferation.
AB  - The ubiquitously expressed phosphatidylinositol binding clathrin assembly
      (PICALM) protein associates with the plasma membrane, binds clathrin, and plays a
      role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are
      present in aggressive hematopoietic malignancies, and genome-wide association
      studies have recently linked the PICALM locus to late-onset Alzheimer's disease.
      Inactivating and hypomorphic Picalm mutations in mice cause different degrees of
      severity of anemia, abnormal iron metabolism, growth retardation and shortened
      lifespan. To understand PICALM's function, we studied the consequences of PICALM
      overexpression and characterized PICALM-deficient cells derived from mutant fit1
      mice. Our results identify a role for PICALM in transferrin receptor (TfR)
      internalization and demonstrate that the C-terminal PICALM residues are critical
      for its association with clathrin and for the inhibitory effect of PICALM
      overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs) that
      are deficient in PICALM display several characteristics of iron deficiency
      (increased surface TfR expression, decreased intracellular iron levels, and
      reduced cellular proliferation), all of which are rescued by retroviral PICALM
      expression. The proliferation defect of cells that lack PICALM results, at least
      in part, from insufficient iron uptake, since it can be corrected by iron
      supplementation. Moreover, PICALM-deficient cells are particularly sensitive to
      iron chelation. Taken together, these data reveal that PICALM plays a critical
      role in iron homeostasis, and offer new perspectives into the pathogenesis of
      PICALM-associated diseases.

PMID- 22952942
TI  - Gene silencing of FANCF potentiates the sensitivity to mitoxantrone through
      activation of JNK and p38 signal pathways in breast cancer cells.
AB  - Fanconi anemia complementation group-F (FANCF) is a key factor to maintain the
      function of FA/BRCA, a DNA-damage response pathway. However, the functional role
      of FANCF in breast cancer has not been elucidated. In this study, we examined the
      effects and mechanisms of FANCF-RNAi on the sensitivity of breast cancer cells to
      mitoxantrone (MX). FANCF silencing by FANCF-shRNA blocked functions of FA/BRCA
      pathway through inhibition of FANCD2 mono-ubiquitination in breast cancer cell
      lines MCF-7 and T-47D. In addition, FANCF shRNA inhibited cell proliferation,
      induced apoptosis, and chromosome fragmentation in both breast cancer cells. We
      also found that FANCF silencing potentiated the sensitivity to MX in breast
      cancer cells, accompanying with an increase in intracellular MX accumulation and
      a decrease in BCRP expression. Furthermore, we found that the blockade of FA/BRCA
      pathway by FANCF-RNAi activated p38 and JNK MAPK signal pathways in response to
      MX treatment. BCRP expression was restored by p38 inhibitor SB203580, but not by
      JNK inhibitor SP600125. FANCF silencing increased JNK and p38 mediated activation
      of p53 in MX-treated breast cancer cells, activated the mitochondrial apoptosis
      pathway. Our findings indicate that FANCF shRNA potentiates the sensitivity of
      breast cancer cells to MX, suggesting that FANCF may be a potential target for
      therapeutic strategies for the treatment of breast tumors.

PMID- 22952943
TI  - Ambient pH controls glycogen levels by regulating glycogen synthase gene
      expression in Neurospora crassa. New insights into the pH signaling pathway.
AB  - Glycogen is a polysaccharide widely distributed in microorganisms and animal
      cells and its metabolism is under intricate regulation. Its accumulation in a
      specific situation results from the balance between glycogen synthase and
      glycogen phosphorylase activities that control synthesis and degradation,
      respectively. These enzymes are highly regulated at transcriptional and post
      translational levels. The existence of a DNA motif for the Aspergillus nidulans
      pH responsive transcription factor PacC in the promoter of the gene encoding
      glycogen synthase (gsn) in Neurospora crassa prompted us to investigate whether
      this transcription factor regulates glycogen accumulation. Transcription factors
      such as PacC in A. nidulans and Rim101p in Saccharomyces cerevisiae play a role
      in the signaling pathway that mediates adaptation to ambient pH by inducing the
      expression of alkaline genes and repressing acidic genes. We showed here that at
      pH 7.8 pacC was over-expressed and gsn was down-regulated in wild-type N. crassa
      coinciding with low glycogen accumulation. In the pacC(KO) strain the glycogen
      levels and gsn expression at alkaline pH were, respectively, similar to and
      higher than the wild-type strain at normal pH (5.8). These results characterize
      gsn as an acidic gene and suggest a regulatory role for PACC in gsn expression.
      The truncated recombinant protein, containing the DNA-binding domain specifically
      bound to a gsn DNA fragment containing the PacC motif. DNA-protein complexes were
      observed with extracts from cells grown at normal and alkaline pH and confirmed
      by ChIP-PCR analysis. The PACC present in these extracts showed equal molecular
      mass, indicating that the protein is already processed at normal pH, in contrast
      to A. nidulans. Together, these results show that the pH signaling pathway
      controls glycogen accumulation by regulating gsn expression and suggest the
      existence of a different mechanism for PACC activation in N. crassa.

PMID- 22952944
TI  - Easy fabrication of thin membranes with through holes. Application to protein
      patterning.
AB  - Since protein patterning on 2D surfaces has emerged as an important tool in cell
      biology, the development of easy patterning methods has gained importance in
      biology labs. In this paper we present a simple, rapid and reliable technique to
      fabricate thin layers of UV curable polymer with through holes. These membranes
      are as easy to fabricate as microcontact printing stamps and can be readily used
      for stencil patterning. We show how this microfabrication scheme allows highly
      reproducible and highly homogeneous protein patterning with micron sized
      resolution on surfaces as large as 10 cm(2). Using these stencils, fragile
      proteins were patterned without loss of function in a fully hydrated state. We
      further demonstrate how intricate patterns of multiple proteins can be achieved
      by stacking the stencil membranes. We termed this approach microserigraphy.

PMID- 22952945
TI  - The impact of successful cataract surgery on quality of life, household income
      and social status in South India.
AB  - BACKGROUND: To explore the hypothesis that sight restoring cataract surgery
      provided to impoverished rural communities will improve not only visual acuity
      and vision-related quality of life (VRQoL) but also poverty and social status.
      METHODS: Participants were recruited at outreach camps in Tamil Nadu, South
      India, and underwent free routine manual small incision cataract surgery (SICS)
      with intra-ocular lens (IOL) implantation, and were followed up one year later.
      Poverty was measured as monthly household income, being engaged in income
      generating activities and number of working household members. Social status was
      measured as rates of re-marriage amongst widowed participants. VRQoL was measured
      using the IND-VFQ-33. Associations were explored using logistic regression (SPSS
      19). RESULTS: Of the 294 participants, mean age +/- standard deviation (SD) 60 +/
      8 years, 54% men, only 11% remained vision impaired at follow up (67% at
      baseline; p<0.001). At one year, more participants were engaged in income
      generating activities (44.7% to 77.7%; p<0.001) and the proportion of households
      with a monthly income <1000 Rps. decreased from 50.5% to 20.5% (p<0.05). Overall
      VRQoL improved (p<0.001). Participants who had successful cataract surgery were
      less likely to remain in the lower categories of monthly household income (OR
      0.05-0.22; p<0.02) and more likely to be engaged in income earning activities one
      year after surgery (OR 3.28; p = 0.006). Participants widowed at baseline who had
      successful cataract surgery were less likely to remain widowed at one year (OR
      0.02; p = 0.008). CONCLUSION: These findings indicate the broad positive impact
      of sight restoring cataract surgery on the recipients' as well as their families'
      lives. Providing free high quality cataract surgery to marginalized rural
      communities will not only alleviate avoidable blindness but also - to some extent
      - poverty in the long run.

PMID- 22952946
TI  - Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury
      in the Fischer 344 rat.
AB  - Current human reproductive risk assessment methods rely on semen and serum
      hormone analyses, which are not easily comparable to the histopathological
      endpoints and mating studies used in animal testing. Because of these
      limitations, there is a need to develop universal evaluations that reliably
      reflect male reproductive function. We hypothesized that toxicant-induced
      testicular injury can be detected in sperm using mRNA transcripts as indicators
      of insult. To test this, we exposed adult male Fischer 344 rats to low doses of
      model testicular toxicants and classically characterized the testicular injury
      while simultaneously evaluating sperm mRNA transcripts from the same animals.
      Overall, this study aimed to: 1) identify sperm transcripts altered after
      exposure to the model testicular toxicant, 2,5-hexanedione (HD) using
      microarrays; 2) expand on the HD-induced transcript changes in a comprehensive
      time course experiment using qRT-PCR arrays; and 3) test these injury indicators
      after exposure to another model testicular toxicant, carbendazim (CBZ).
      Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered
      sperm mRNA transcripts when compared to control using linear models of microarray
      analysis (q<0.05). All transcript alterations disappeared after 3 months of post
      exposure recovery. In the time course experiment, time-dependent alterations were
      observed for 12 candidate transcripts selected from the microarray data based
      upon fold change and biological relevance, and 8 of these transcripts remained
      significantly altered after the 3-month recovery period (p<0.05). In the last
      experiment, 8 candidate transcripts changed after exposure to CBZ (p<0.05). The
      two testicular toxicants produced distinct molecular signatures with only 4
      overlapping transcripts between them, each occurring in opposite directions.
      Overall, these results suggest that sperm mRNA transcripts are indicators of low
      dose toxicant-induced testicular injury in the rat.

PMID- 22952947
TI  - A yeast metabolite extraction protocol optimised for time-series analyses.
AB  - There is an increasing call for the absolute quantification of time-resolved
      metabolite data. However, a number of technical issues exist, such as metabolites
      being modified/degraded either chemically or enzymatically during the extraction
      process. Additionally, capillary electrophoresis mass spectrometry (CE-MS) is
      incompatible with high salt concentrations often used in extraction protocols. In
      microbial systems, metabolite yield is influenced by the extraction protocol used
      and the cell disruption rate. Here we present a method that rapidly quenches
      metabolism using dry-ice ethanol bath and methanol N-ethylmaleimide solution
      (thus stabilising thiols), disrupts cells efficiently using bead-beating and
      avoids artefacts created by live-cell pelleting. Rapid sample processing
      minimised metabolite leaching. Cell weight, number and size distribution was used
      to calculate metabolites to an attomol/cell level. We apply this method to
      samples obtained from the respiratory oscillation that occurs when yeast are
      grown continuously.

PMID- 22952948
TI  - Eradication of Pseudomonas aeruginosa biofilms by atmospheric pressure non
      thermal plasma.
AB  - Bacteria exist, in most environments, as complex, organised communities of
      sessile cells embedded within a matrix of self-produced, hydrated extracellular
      polymeric substances known as biofilms. Bacterial biofilms represent a ubiquitous
      and predominant cause of both chronic infections and infections associated with
      the use of indwelling medical devices such as catheters and prostheses. Such
      infections typically exhibit significantly enhanced tolerance to antimicrobial,
      biocidal and immunological challenge. This renders them difficult, sometimes
      impossible, to treat using conventional chemotherapeutic agents. Effective
      alternative approaches for prevention and eradication of biofilm associated
      chronic and device-associated infections are therefore urgently required.
      Atmospheric pressure non-thermal plasmas are gaining increasing attention as a
      potential approach for the eradication and control of bacterial infection and
      contamination. To date, however, the majority of studies have been conducted with
      reference to planktonic bacteria and rather less attention has been directed
      towards bacteria in the biofilm mode of growth. In this study, the activity of a
      kilohertz-driven atmospheric pressure non-thermal plasma jet, operated in a
      helium oxygen mixture, against Pseudomonas aeruginosa in vitro biofilms was
      evaluated. Pseudomonas aeruginosa biofilms exhibit marked susceptibility to
      exposure of the plasma jet effluent, following even relatively short (~ 10's s)
      exposure times. Manipulation of plasma operating conditions, for example, plasma
      operating frequency, had a significant effect on the bacterial inactivation rate.
      Survival curves exhibit a rapid decline in the number of surviving cells in the
      first 60 seconds followed by slower rate of cell number reduction. Excellent anti
      biofilm activity of the plasma jet was also demonstrated by both confocal
      scanning laser microscopy and metabolism of the tetrazolium salt, XTT, a measure
      of bactericidal activity.

PMID- 22952949
TI  - Dissociable spatial and temporal effects of inhibition of return.
AB  - Inhibition of return (IOR) refers to the relative suppression of processing at
      locations that have recently been attended. It is frequently explored using a
      spatial cueing paradigm and is characterized by slower responses to cued than to
      uncued locations. The current study investigates the impact of IOR on overt
      visual orienting involving saccadic eye movements. Using a spatial cueing
      paradigm, our experiments have demonstrated that at a cue-target onset asynchrony
      (CTOA) of 400 ms saccades to the vicinity of cued locations are not only delayed
      (temporal cost) but also biased away (spatial effect). Both of these effects are
      basically no longer present at a CTOA of 1200 ms. At a shorter 200 ms CTOA, the
      spatial effect becomes stronger while the temporal cost is replaced by a temporal
      benefit. These findings suggest that IOR has a spatial effect that is dissociable
      from its temporal effect. Simulations using a neural field model of the superior
      colliculus (SC) revealed that a theory relying on short-term depression (STD) of
      the input pathway can explain most, but not all, temporal and spatial effects of
      IOR.

PMID- 22952950
TI  - Effects of fishing and regional species pool on the functional diversity of fish
      communities.
AB  - The potential population and community level impacts of fishing have received
      considerable attention, but little is known about how fishing influences
      communities' functional diversity at regional scales. We examined how estimates
      of functional diversity differed among 25 regions of variable richness and
      investigated the functional consequences of removing species targeted by
      commercial fisheries. Our study shows that fishing leads to substantial losses in
      functional diversity. The magnitude of such loss was, however, reduced in the
      more speciose regions. Moreover, the removal of commercially targeted species
      caused a much larger reduction in functional diversity than expected by random
      species deletions, which was a consequence of the selective nature of fishing for
      particular species traits. Results suggest that functional redundancy is
      spatially variable, that richer biotas provide some degree of insurance against
      the impact of fishing on communities' functional diversity and that fishing
      predominantly selects for particular species traits. Understanding how fishing
      impacts community functional diversity is key to predict its effects for
      biodiversity as well as ecosystem functioning.

PMID- 22952951
TI  - Human endometrial stromal stem cells differentiate into megakaryocytes with the
      ability to produce functional platelets.
AB  - Human endometrium is a high dynamic tissue that contains endometrial stromal stem
      cells (hESSCs). The hESSCs have been differentiated into a number of cell
      lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not
      yet been investigated. The aim of this study was to investigate the feasibility
      of MK generation from hESSCs and subsequent production of functional platelets
      (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as
      confirmed by positive stromal cell specific markers (CD90 and CD29) and negative
      hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were
      differentiated in a medium supplemented with thrombopoietin (TPO) for 18 days.
      The MK differentiation was analyzed by flow cytometry and confocal microscopy.
      The differentiation medium was collected for PLT production analysis by flow
      cytometry, transmission electron microscopy and functional measurements. Our
      results show: 1) MKs were successfully generated from hESSCs as identified by
      expression of specific markers (CD41a: 1 +/- 0.09% and 39 +/- 3.0%; CD42b: 1.2 +/
      0.06% and 28 +/- 2.0%, control vs. differentiation) accompanied with reduction
      of pluripotent transcription factors (Oct4 and Sox2) expression; 2) The level of
      PLTs in the differentiation medium was 16 +/- 1 number/ul as determined by size
      (2-4 um) and CD41a expression (CD41a: 1 +/- 0.4% and 90+/-2.0%, control vs.
      differentiation); 3) Generated PLTs were functional as evidenced by the up
      regulation of CD62p expression and fibrinogen binding following thrombin
      stimulation; 4) Released PLTs showed similar ultra-structure characteristics
      (alpha granules, vacuoles and dense tubular system) as PLTs from peripheral blood
      determined by electron microscopic analysis. Data demonstrate the feasibility of
      generating MKs from hESSCs, and that the generated MKs release functional PLTs.
      Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT
      production.

PMID- 22952953
TI  - The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker:
      adipophilin.
AB  - BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human
      tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets
      which are visible in the cytoplasm of neoplastic cells in cytological
      preparations. These vacuoles are not identifiable in biopsy section as lipids are
      "lost" during tissue processing. METHODS AND RESULTS: In this study we
      investigated the expression of genes involved in lipid metabolism, at both RNA
      and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma
      cases. Gene expression profile indicated a significant over-expression of the
      adipophilin gene and marked up-regulation of other genes involved in lipid
      metabolism in Burkitt lymphoma. These findings were confirmed by
      immunohistochemistry on a series od additional histological samples: 45 out of 47
      BL cases showed strong adipophilin expression, while only 3 cases of the 33 of
      the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05).
      CONCLUSIONS: Our preliminary results suggest that lipid metabolism is altered in
      BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be
      specifically recognized by a monoclonal antibody against adipophilin, which may
      therefore be a useful marker for Burkitt lymphoma because of its peculiar
      expression pattern. Moreover this peptide might represent an interesting
      candidate for interventional strategies.

PMID- 22952952
TI  - An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces
      cell death by inhibiting microtubule dynamics.
AB  - Using cell based screening assay, we identified a novel anti-tubulin agent (Z)-5
      ((5-(4-bromo-3-chlorophenyl)furan-2-yl)methylene)-2-thioxothiazolidin-4-one
      (BCFMT) that inhibited proliferation of human cervical carcinoma (HeLa) (IC(50),
      7.2 +/- 1.8 uM), human breast adenocarcinoma (MCF-7) (IC(50), 10.0 +/- 0.5 uM),
      highly metastatic breast adenocarcinoma (MDA-MB-231) (IC(50), 6.0 +/- 1 uM),
      cisplatin-resistant human ovarian carcinoma (A2780-cis) (IC(50), 5.8 +/- 0.3 uM)
      and multi-drug resistant mouse mammary tumor (EMT6/AR1) (IC(50), 6.5 +/- 1 uM)
      cells. Using several complimentary strategies, BCFMT was found to inhibit cancer
      cell proliferation at G2/M phase of the cell cycle apparently by targeting
      microtubules. In addition, BCFMT strongly suppressed the dynamics of individual
      microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory
      concentration (10 uM), BCFMT reduced the rates of growing and shortening phases
      of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased
      the time microtubules spent in the pause (neither growing nor shortening
      detectably) state by 135% and reduced the dynamicity (dimer exchange per unit
      time) of microtubules by 70%. In vitro, BCFMT bound to tubulin with a
      dissociation constant of 8.3 +/- 1.8 uM, inhibited tubulin assembly and
      suppressed GTPase activity of microtubules. BCFMT competitively inhibited the
      binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration
      (K(i)) of 5.2 +/- 1.5 uM suggesting that it binds to tubulin at the vinblastine
      site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules,
      perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and
      Mad2) at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear
      accumulation of p53 and its downstream p21, which consequently activated
      apoptosis in these cells. The results suggested that BCFMT inhibits proliferation
      of several types of cancer cells including drug resistance cells by suppressing
      microtubule dynamics and indicated that the compound may have chemotherapeutic
      potential.

PMID- 22952954
TI  - The proliferation index of specific bone marrow cell compartments from
      myelodysplastic syndromes is associated with the diagnostic and patient outcome.
AB  - Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently
      show a hypercellular dysplastic bone marrow (BM) associated with inefficient
      hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation
      blockades. Currently, little is known about the role of cell proliferation in
      compensating for the BM failure syndrome and in determining patient outcome.
      Here, we analyzed the proliferation index (PI) of different compartments of BM
      hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n =
      94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow
      cytometry. Our results show abnormally increased overall BM proliferation
      profiles in MDS which significantly differ between early/low-risk and
      advanced/high-risk cases. Early/low-risk patients showed increased proliferation
      of non-lymphoid CD34(+) precursors, maturing neutrophils and nucleated red blood
      cells (NRBC), while the PI of these compartments of BM precursors progressively
      fell below normal values towards AML levels in advanced/high-risk MDS. Decreased
      proliferation of non-lymphoid CD34(+) and NRBC precursors was significantly
      associated with adverse disease features, shorter overall survival (OS) and
      transformation to AML, both in the whole series and when low- and high-risk MDS
      patients were separately considered, the PI of NRBC emerging as the most powerful
      independent predictor for OS and progression to AML. In conclusion, assessment of
      the PI of NRBC, and potentially also of other compartments of BM precursors
      (e.g.: myeloid CD34(+) HPC), could significantly contribute to a better
      management of MDS.

PMID- 22952955
TI  - Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances
      its virulence: possible role in anastomotic leak.
AB  - The most feared complication following intestinal resection is anastomotic
      leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation
      is used, the incidence of anastomotic leaks remains unacceptably high (~ 10%)
      even when performed by specialist surgeons in high volume centers. The aims of
      this study were to test the hypothesis that anastomotic leakage develops when
      pathogens colonizing anastomotic sites become in vivo transformed to express a
      tissue destroying phenotype. We developed a novel model of anastomotic leak in
      which rats were exposed to pre-operative radiation as in cancer surgery,
      underwent distal colon resection and then were intestinally inoculated with
      Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results
      demonstrated that intestinal tissues exposed to preoperative radiation developed
      a significant incidence of anastomotic leak (>60%; p<0.01) when colonized by P.
      aeruginosa compared to radiated tissues alone (0%). Phenotype analysis comparing
      the original inoculating strain (MPAO1- termed P1) and the strain retrieved from
      leaking anastomotic tissues (termed P2) demonstrated that P2 was altered in
      pyocyanin production and displayed enhanced collagenase activity, high swarming
      motility, and a destructive phenotype against cultured intestinal epithelial
      cells (i.e. apoptosis, barrier function, cytolysis). Comparative genotype
      analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP)
      mutation in the mexT gene that led to a stop codon resulting in a non-functional
      truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the
      original parental strain P1 led to reversion of P2 to the P1 phenotype. No
      spontaneous transformation was detected during 20 passages in TSB media. Use of a
      novel virulence suppressing compound PEG/Pi prevented P. aeruginosa
      transformation to the tissue destructive phenotype and prevented anastomotic leak
      in rats. This work demonstrates that in vivo transformation of microbial
      pathogens to a tissue destroying phenotype may have important implications in the
      pathogenesis of anastomotic leak.

PMID- 22952956
TI  - Conflict of interest in spine research reporting.
AB  - BACKGROUND: Medical studies are more likely to report favorable findings when a
      conflict of interest is declared. We aim to quantify and determine the effect of
      author disclosure of conflict of interest on scientific reporting. METHODS:
      Abstracts from an international spine research meeting (North American Spine
      Society 2010) were selected that specifically evaluated a device, biologic, or
      proprietary procedure. They were then made anonymous to reviewers. An item of
      interest was established in each of the abstracts in order to standardize
      evaluation. Next, three blinded reviewers independently rated the abstracts as
      favorable, neutral, or unfavorable with regard to the item of interest.
      Additionally, the blinded reviewers attempted to predict whether a related
      disclosure was made. The meeting disclosure index was used to tabulate the
      minimum US dollar value attributable to disclosures. RESULTS: Of the 344 total
      abstracts, 76 met inclusion criteria. In 79%, a related conflict of interest was
      reported. The amount of the disclosure was incompletely reported in 30% of cases.
      Where available, it averaged a cumulative minimum of $219,634 USD per abstract.
      The results of the abstracts were judged to be favorable, neutral, and
      unfavorable in 63%, 32% and 5% of abstracts, respectively. There was no
      correlation between the presence of a related disclosure and the findings of the
      studies (p = 0.81), although interpretation of this is limited by a small sample
      size and an overall apparent bias to report favorable studies. Additionally, the
      blinded reviewers were unable to predict whether a related disclosure was made (p
      = 0.40). CONCLUSION: No association existed between the presence of a related
      disclosure and the results of the studies. While the actual compliance with
      reporting a potential conflict of interest is unable to be determined, the value
      amount related to the disclosures made was inadequately reported according to
      meeting guidelines.

PMID- 22952957
TI  - Comparisons of three methods for organic and inorganic carbon in calcareous soils
      of northwestern China.
AB  - With increasing interest in the carbon cycle on arid land, there is an urgent
      need to quantify both soil organic carbon (SOC) and inorganic carbon (SIC) thus
      to assess various methods. Here, we present a study employing three methods for
      determinations of SOC and SIC in the Yanqi Basin of northwest China. We use an
      elemental analyzer for both SOC and SIC, the Walkley-Black method for SOC, a
      modified pressure calcimeter method for SIC, and a simple loss-on-ignition (LOI)
      procedure for determinations of SOC and SIC. Our analyses show that all three
      approaches produce consistently low values for SOC (1-14 g kg(-1)) and high
      values for SIC (8-53 g kg(-1)). The Walkley-Black method provides an accurate
      estimate of SOC with 100% recovery for most soil samples. The pressure calcimeter
      method is as accurate as the elemental analysis for measuring SIC. In addition,
      SOC and SIC can be accurately estimated using a two-step LOI approach, i.e., (1)
      combustion at 375 degrees C for 17 hours to estimate SOC, and (2) subsequent
      combustion at 800 degrees C for 12 hours to estimate SIC. There are strong linear
      relationships for both SOC and SIC between the elemental analysis and LOI method,
      which demonstrates the capability of the two-step LOI technique for estimating
      SOC and SIC in this arid region.

PMID- 22952958
TI  - Combination of multiple resistance traits from wild relative species in
      Chrysanthemum via trigeneric hybridization.
AB  - BACKGROUND: With the objective of combining multiple resistant traits from wild
      relative species in florist's chrysanthemums, trigeneric hybridization was
      conducted by crossing two intergeneric F(1) hybrids Chrysanthemum grandiflorum *
      Artemisia vulgaris and Chrysanthemum crassum * Crossostephium chinense.
      METHODOLOGY/PRINCIPAL FINDINGS: To assess post-pollination phenomena, we
      investigated pollen germination on the stigma and embryo development, using
      fluorescence and scanning electron microscopy and paraffin-embedded sections,
      respectively. We selected eight putative trigeneric hybrid lines that showed the
      greatest morphological differences from the parents from among the progeny
      derived via embryo rescue. The hybridity of one trigeneric hybrid was further
      confirmed by fluorescent genomic in situ hybridization; in addition, the aphid
      resistance and salt tolerance of this hybrid were higher than those of the
      chrysanthemum parent and the C. grandiflorum * A. vulgaris F(1) hybrid,
      respectively. CONCLUSIONS/SIGNIFICANCE: The enhanced aphid resistance of the
      hybrid line reflects the inheritance of chromosomes from A. vulgaris, which
      carries genes that encode bioactive components. The enhanced salt tolerance of
      the trigeneric hybrid is attributable to inheritance of genetic materials from
      Chrysanthemum crassum and Crossostephium chinense, which act to maintain the
      compartmentation of Na(+) and K(+) ions and their selective transportation among
      different organs to avert deleterious effects and protect the photosynthetic
      apparatus. The results indicate that trigeneric hybridization between different
      bigeneric hybrids is a promising method for combination of multiple stress
      resistance traits for improvement of chrysanthemum.

PMID- 22952959
TI  - Expression of osteoprotegerin in placenta and its association with preeclampsia.
AB  - BACKGROUND: Osteoprotegerin (OPG), a key regulatory factor in bone metabolism,
      was documented also a potential pro-angiogenic factor, which acts an important
      role in protecting vascular endothelial cells. Since preeclampsia has gradually
      been employed to be vascular diseases, we speculated that OPG might be associated
      with preeclampsia. The study was to evaluate the level of OPG protein and mRNA in
      placenta, and investigate the relationship between OPG and the pathogenesis of
      preeclampsia. METHODOLOGY/PRINCIPAL FINDINGS: Placental specimens from 30 term
      normal pregnancy, 30 severe preeclampsia and 30 mild cases were studied. The
      expression and levels of OPGs' protein and mRNA were detected by
      immunohistochemistry, western blot analysis and real-time quantitative PCR
      analysis respectively. The expression of OPG protein was found in cytoplasm of
      placenta cytotrophoblasts and syncytiotrophoblasts in three groups. There were no
      significant differences of OPG protein between the maternal and fetal side in
      each group. The OPG protein and mRNA levels in severe preeclampsia were
      significantly higher than those in mild cases and normal pregnancy. However,
      there were no markedly differences of the OPG protein and mRNA levels between
      term delivery and preterm delivery in severe cases. In preeclampsia, the OPG
      protein and mRNA level was positively correlated with systolic blood pressure and
      24 h urinary protein respectively. CONCLUSIONS/SIGNIFICANCE: OPG protein and mRNA
      level in placentas of preeclampsia were found abnormal compared with normal
      pregnancy. In preeclampsia, the OPG protein and mRNA levels were closely related
      with its important clinical parameters. Taken together, OPG might be closely
      correlated with the pathogenesis of preeclampsia.

PMID- 22952961
TI  - Elastic modulus of muscle and tendon with shear wave ultrasound elastography:
      variations with different technical settings.
AB  - Standardization on Shear wave ultrasound elastography (SWUE) technical settings
      will not only ensure that the results are accurate, but also detect any
      differences over time that may be attributed to true physiological changes. The
      present study evaluated the variations of elastic modulus of muscle and tendon
      using SWUE when different technical aspects were altered. The results of this
      study indicated that variations of elastic modulus of muscle and tendon were
      found when different transducer's pressure and region of interest (ROI)'s size
      were applied. No significant differences in elastic modulus of the rectus femoris
      muscle and patellar tendon were found with different acquisition times of the
      SWUE sonogram. The SWUE on the muscle and tendon should be performed with the
      lightest transducer's pressure, a shorter acquisition time for the SWUE sonogram,
      while measuring the mean elastic modulus regardless the ROI's size.

PMID- 22952960
TI  - Brain-derived neurotrophic factor enhances calcium regulatory mechanisms in human
      airway smooth muscle.
AB  - Neurotrophins (NTs), which play an integral role in neuronal development and
      function, have been found in non-neuronal tissue (including lung), but their role
      is still under investigation. Recent reports show that NTs such as brain-derived
      neurotrophic factor (BDNF) as well as NT receptors are expressed in human airway
      smooth muscle (ASM). However, their function is still under investigation. We
      hypothesized that NTs regulate ASM intracellular Ca(2+) ([Ca(2+)](i)) by altered
      expression of Ca(2+) regulatory proteins. Human ASM cells isolated from lung
      samples incidental to patient surgery were incubated for 24 h (overnight) in
      medium (control) or 1 nM BDNF in the presence vs. absence of inhibitors of
      signaling cascades (MAP kinases; PI3/Akt; NFkappaB). Measurement of [Ca(2+)](i)
      responses to acetylcholine (ACh) and histamine using the Ca(2+) indicator fluo-4
      showed significantly greater responses following BDNF exposure: effects that were
      blunted by pathway inhibitors. Western analysis of whole cell lysates showed
      significantly higher expression of CD38, Orai1, STIM1, IP(3) and RyR receptors,
      and SERCA following BDNF exposure, effects inhibited by inhibitors of the above
      cascades. The functional significance of BDNF effects were verified by siRNA or
      pharmacological inhibition of proteins that were altered by this NT. Overall,
      these data demonstrate that NTs activate signaling pathways in human ASM that
      lead to enhanced [Ca(2+)](i) responses via increased regulatory protein
      expression, thus enhancing airway contractility.

PMID- 22952962
TI  - Model to track wild birds for avian influenza by means of population dynamics and
      surveillance information.
AB  - Design, sampling and data interpretation constitute an important challenge for
      wildlife surveillance of avian influenza viruses (AIV). The aim of this study was
      to construct a model to improve and enhance identification in both different
      periods and locations of avian species likely at high risk of contact with AIV in
      a specific wetland. This study presents an individual-based stochastic model for
      the Ebre Delta as an example of this appliance. Based on the Monte-Carlo method,
      the model simulates the dynamics of the spread of AIV among wild birds in a
      natural park following introduction of an infected bird. Data on wild bird
      species population, apparent AIV prevalence recorded in wild birds during the
      period of study, and ecological information on factors such as behaviour, contact
      rates or patterns of movements of waterfowl were incorporated as inputs of the
      model. From these inputs, the model predicted those species that would introduce
      most of AIV in different periods and those species and areas that would be at
      high risk as a consequence of the spread of these AIV incursions. This method can
      serve as a complementary tool to previous studies to optimize the allocation of
      the limited AI surveillance resources in a local complex ecosystem. However, this
      study indicates that in order to predict the evolution of the spread of AIV at
      the local scale, there is a need for further research on the identification of
      host factors involved in the interspecies transmission of AIV.

PMID- 22952963
TI  - A single molecule investigation of the photostability of quantum dots.
AB  - Quantum dots (QDs) are very attractive probes for multi-color fluorescence
      imaging in biological applications because of their immense brightness and
      reported extended photostability. We report here however that single QDs,
      suitable for biological applications, that are subject to continuous blue
      excitation from a conventional 100 W mercury arc lamp will undergo a continuous
      blue-switching of the emission wavelength eventually reaching a permanent dark,
      photobleached state. We further show that beta-mercaptoethanol has a dual
      stabilizing effect on the fluorescence emission of QDs: 1) by increasing the
      frequency of time that a QD is in its fluorescent state, and 2) by decreasing the
      photobleaching rate. The observed QD color spectral switching is especially
      detrimental for multi-color single molecule applications, as we regularly observe
      spectral blue-shifts of 50 nm, or more even after only ten seconds of
      illumination. However, of significant importance for biological applications, we
      find that even small, biologically compatible, concentrations (25 uM) of beta
      mercaptoethanol has a significant stabilizing effect on the emission color of
      QDs, but that greater amounts are required to completely abolish the spectral
      blue shifting or to minimize the emission intermittency of QDs.

PMID- 22952964
TI  - Productivity and time use during occupational therapy and nutrition/dietetics
      clinical education: a cohort study.
AB  - BACKGROUND: Currently in the Australian higher education sector higher
      productivity from allied health clinical education placements is a contested
      issue. This paper will report results of a study that investigated output changes
      associated with occupational therapy and nutrition/dietetics clinical education
      placements in Queensland, Australia. Supervisors' and students' time use during
      placements and how this changes for supervisors compared to when students are not
      present in the workplace is also presented. METHODOLOGY/PRINCIPAL FINDINGS: A
      cohort design was used with students from four Queensland universities, and their
      supervisors employed by Queensland Health. There was an increasing trend in the
      number of occasions of service delivered when the students were present, and a
      statistically significant increase in the daily mean length of occasions of
      service delivered during the placement compared to pre-placement levels.
      CONCLUSIONS/SIGNIFICANCE: A novel method for estimating productivity and time use
      changes during clinical education programs for allied health disciplines has been
      applied. During clinical education placements there was a net increase in
      outputs, suggesting supervisors engage in longer consultations with patients for
      the purpose of training students, while maintaining patient numbers. Other
      activities were reduced. This paper is the first time these data have been shown
      in Australia and form a sound basis for future assessments of the economic impact
      of student placements for allied health disciplines.

PMID- 22952965
TI  - Implications of pyrosequencing error correction for biological data
      interpretation.
AB  - There has been a rapid proliferation of approaches for processing and
      manipulating second generation DNA sequence data. However, users are often left
      with uncertainties about how the choice of processing methods may impact
      biological interpretation of data. In this report, we probe differences in output
      between two different processing pipelines: a de-noising approach using the
      AmpliconNoise algorithm for error correction, and a standard approach using
      quality filtering and preclustering to reduce error. There was a large overlap in
      reads culled by each method, although AmpliconNoise removed a greater net number
      of reads. Most OTUs produced by one method had a clearly corresponding partner in
      the other. Although each method resulted in OTUs consisting entirely of reads
      that were culled by the other method, there were many more such OTUs formed in
      the standard pipeline. Total OTU richness was reduced by AmpliconNoise
      processing, but per-sample OTU richness, diversity and evenness were increased.
      Increases in per-sample richness and diversity may be a result of AmpliconNoise
      processing producing a more even OTU rank-abundance distribution. Because
      communities were randomly subsampled to equalize sample size across communities,
      and because rare sequence variants are less likely to be selected during
      subsampling, fewer OTUs were lost from individual communities when subsampling
      AmpliconNoise-processed data. In contrast to taxon-based diversity estimates,
      phylogenetic diversity was reduced even on a per-sample basis by de-noising, and
      samples switched widely in diversity rankings. This work illustrates the
      significant impacts of processing pipelines on the biological interpretations
      that can be made from pyrosequencing surveys. This study provides important
      cautions for analyses of contemporary data, for requisite data archiving
      (processed vs. non-processed data), and for drawing comparisons among studies
      performed using distinct data processing pipelines.

PMID- 22952967
TI  - Recurrent disturbances and the degradation of hard coral communities in Taiwan.
AB  - Recurrent disturbances can have a critical effect on the structure and function
      of coral reef communities. In this study, long-term changes were examined in the
      hard coral community at Wanlitung, in southern Taiwan, between 1985 and 2010. In
      this 26 year interval, the reef has experienced repeated disturbances that
      include six typhoons and two coral-bleaching events. The frequency of disturbance
      has meant that species susceptible to disturbance, such as those in the genus
      Acropora and Montipora have almost disappeared from the reef. Indeed, almost all
      hard coral species have declined in abundance, with the result that total hard
      coral cover in 2010 (17.7%) was less than half what it was in 1985 (47.5%). In
      addition, macro-algal cover has increased from 11.3% in 2003 to 28.5% in 2010.
      The frequency of disturbance combined with possible chronic influence of a
      growing human population mean that a diverse reef assemblage is unlikely to
      persist on this reef into the future.

PMID- 22952966
TI  - Cortactin is a substrate of activated Cdc42-associated kinase 1 (ACK1) during
      ligand-induced epidermal growth factor receptor downregulation.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) internalization following
      ligand binding controls EGFR downstream pathway signaling activity. Internalized
      EGFR is poly-ubiquitinated by Cbl to promote lysosome-mediated degradation and
      signal downregulation. ACK1 is a non-receptor tyrosine kinase that interacts with
      ubiquitinated EGFR to facilitate EGFR degradation. Dynamic reorganization of the
      cortical actin cytoskeleton controlled by the actin related protein (Arp)2/3
      complex is important in regulating EGFR endocytosis and vesicle trafficking. How
      ACK1-mediated EGFR internalization cooperates with Arp2/3-based actin dynamics
      during EGFR downregulation is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      show that ACK1 directly binds and phosphorylates the Arp2/3 regulatory protein
      cortactin, potentially providing a direct link to Arp2/3-based actin dynamics
      during EGFR degradation. Co-immunoprecipitation analysis indicates that the
      cortactin SH3 domain is responsible for binding to ACK1. In vitro kinase assays
      demonstrate that ACK1 phosphorylates cortactin on key tyrosine residues that
      create docking sites for adaptor proteins responsible for enhancing Arp2/3
      nucleation. Analysis with phosphorylation-specific antibodies determined that
      EGFR-induced cortactin tyrosine phosphorylation is diminished coincident with
      EGFR degradation, whereas ERK1/2 cortactin phosphorylation utilized in promoting
      activation of the Arp2/3 regulator N-WASp is sustained during EGFR
      downregulation. Cortactin and ACK1 localize to internalized vesicles containing
      EGF bound to EGFR visualized by confocal microscopy. RNA interference and rescue
      studies indicate that ACK1 and the cortactin SH3 domain are essential for ligand
      mediated EGFR internalization. CONCLUSIONS/SIGNIFICANCE: Cortactin is a direct
      binding partner and novel substrate of ACK1. Tyrosine phosphorylation of
      cortactin by ACK1 creates an additional means to amplify Arp2/3 dynamics through
      N-WASp activation, potentially contributing to the overall necessary tensile
      and/or propulsive forces utilized during EGFR endocytic internalization and
      trafficking involved in receptor degradation.

PMID- 22952968
TI  - Evidence that emotion mediates social attention in rhesus macaques.
AB  - BACKGROUND: Recent work on non-human primates indicates that the allocation of
      social attention is mediated by characteristics of the attending animal, such as
      social status and genotype, as well as by the value of the target to which
      attention is directed. Studies of humans indicate that an individual's emotion
      state also plays a crucial role in mediating their social attention; for example,
      individuals look for longer towards aggressive faces when they are feeling more
      anxious, and this bias leads to increased negative arousal and distraction from
      other ongoing tasks. To our knowledge, no studies have tested for an effect of
      emotion state on allocation of social attention in any non-human species.
      METHODOLOGY: We presented captive adult male rhesus macaques with pairs of adult
      male conspecific face images - one with an aggressive expression, one with a
      neutral expression - and recorded gaze towards these images. Each animal was
      tested twice, once during a putatively stressful condition (i.e. following a
      veterinary health check), and once during a neutral (or potentially positive)
      condition (i.e. a period of environmental enrichment). Initial analyses revealed
      that behavioural indicators of anxiety and stress were significantly higher after
      the health check than during enrichment, indicating that the former caused a
      negative shift in emotional state. PRINCIPLE FINDINGS: The macaques showed
      initial vigilance for aggressive faces across both conditions, but subsequent
      responses differed between conditions. Following the health check, initial
      vigilance was followed by rapid and sustained avoidance of aggressive faces. By
      contrast, during the period of enrichment, the macaques showed sustained
      attention towards the same aggressive faces. CONCLUSIONS/SIGNIFICANCE: These data
      provide, to our knowledge, the first evidence that shifts in emotion state
      mediate social attention towards and away from facial cues of emotion in a non
      human animal. This work provides novel insights into the evolution of emotion
      attention interactions in humans, and mechanisms of social behaviour in non-human
      primates, and may have important implications for understanding animal
      psychological wellbeing.

PMID- 22952970
TI  - Content analysis of oncology-related pharmaceutical advertising in a peer
      reviewed medical journal.
AB  - BACKGROUND: The oncology market represents one of the largest pharmaceutical
      markets in any medical field, and printed advertising in medical journals is an
      important channel by which pharmaceutical companies communicate with healthcare
      professionals. The aim of the present study was to analyze the volume and content
      of and trends and changes in oncology-related advertising intended for healthcare
      professionals in a peer-reviewed medical journal. Information that could be
      included in advertisements to promote drug development and improve treatment
      strategies for cancer patients is discussed on the basis of the results of the
      analysis. METHODS/PRINCIPAL FINDINGS: Overall, 6,720 advertisements covering
      13,039 pages in a leading oncology medical journal published (by the American
      Society of Clinical Oncology) between January 2005 and December 2009 were
      analyzed. The advertisements targeting pharmaceuticals and clinical trials, in
      particular, were reviewed. A total of 6,720 advertisements covering 13,039 pages
      were included in the analysis. For the years 2005-2009, the percentages of total
      journal pages dedicated to advertising were 24.0%, 45.7%, 49.8%, 46.8%, and
      49.8%, respectively. Package insert information and efficacy and safety
      explanations appeared in more than 80% of advertisements intended for
      pharmaceutical promotion. From 2005 to 2009, the overall quantity of drug
      advertisements decreased by approximately 13%, whereas advertisements calling for
      the enrollment of patients into registration trials increased by approximately
      11%. CONCLUSION/SIGNIFICANCE: Throughout the study period, oncology-related
      pharmaceutical advertisements occupied a considerable number of pages relative to
      other journal content. The proportion of advertisements on ongoing clinical
      trials increased progressively throughout the study period.

PMID- 22952969
TI  - Investigation of real-time photorepair activity on DNA via surface plasmon
      resonance.
AB  - The cyclobutane pyrimidine dimer (CPD) and 6-4 lesion formations along with the
      specific breaks on strands are the most common type of DNA damage caused by
      Ultraviolet light (UV) irradiation. CPD photolyase I and II construct two
      subfamilies of flavoproteins, which have recognition and repair capabilities of
      CPD sites on both single stranded (ssDNA) and double stranded DNA (dsDNA) with
      the aid of blue light energy. The other types of flavoprotein family consist of
      cryptochromes (CRY) that act as photoreceptors in plants, or circadian rhythm
      regulators in animals. Recent findings showed that a specific type of
      Cryptochrome-Drosophila, Arabidopsis, Synechocystis, Human (CRY-DASH) has
      photorepair activity on ssDNA. In this work, real-time interactions between CRY
      DASH and ss/dsDNA as well as the interactions between Vibrio cholerae photolyase
      (VcPHR) and ss/dsDNA were investigated using Surface Plasmon Resonance (SPR). The
      interactions were then characterized and compared in order to investigate the
      effect of different types of flavoprotein on UV damaged ss/dsDNA. SPR results
      confirm the specific binding of VcPHR and CRY-DASH with UV treated DNA. This
      study is the first instance to quantify the interactions of UV treated and
      untreated DNA with flavoproteins.

PMID- 22952971
TI  - Unexpected high genetic diversity at the extreme northern geographic limit of
      Taurulus bubalis (Euphrasen, 1786).
AB  - The longspined bullhead (Taurulus bubalis, Euphrasen 1786) belongs to the family
      Cottidae and is a rocky shore species that inhabits the intertidal zones of the
      Eastern Atlantic since Iceland, southward to Portugal and also the North Sea and
      Baltic, northward to the Gulf of Finland, with some occurrences in the northern
      Mediterranean coasts eastward to the Gulf of Genoa. We analysed the
      phylogeographic patterns of this species using mitochondrial and nuclear markers
      in populations throughout most of its distributional range in west Europe. We
      found that T. bubalis has a relatively shallow genealogy with some
      differentiation between Atlantic and North Sea. Genetic diversity was homogeneous
      across all populations studied. The possibility of a glacial refugium near the
      North Sea is discussed. In many, but not all, marine temperate organisms,
      patterns of diversity are similar across the species range. If this phenomenon
      proves to be most common in cold adapted species, it may reflect the availability
      of glacial refugia not far from their present-day northern limits.

PMID- 22952972
TI  - Evaluation of new reference genes in papaya for accurate transcript normalization
      under different experimental conditions.
AB  - Real-time reverse transcription PCR (RT-qPCR) is a preferred method for rapid and
      accurate quantification of gene expression studies. Appropriate application of RT
      qPCR requires accurate normalization though the use of reference genes. As no
      single reference gene is universally suitable for all experiments, thus reference
      gene(s) validation under different experimental conditions is crucial for RT-qPCR
      analysis. To date, only a few studies on reference genes have been done in other
      plants but none in papaya. In the present work, we selected 21 candidate
      reference genes, and evaluated their expression stability in 246 papaya fruit
      samples using three algorithms, geNorm, NormFinder and RefFinder. The samples
      consisted of 13 sets collected under different experimental conditions, including
      various tissues, different storage temperatures, different cultivars,
      developmental stages, postharvest ripening, modified atmosphere packaging, 1
      methylcyclopropene (1-MCP) treatment, hot water treatment, biotic stress and
      hormone treatment. Our results demonstrated that expression stability varied
      greatly between reference genes and that different suitable reference gene(s) or
      combination of reference genes for normalization should be validated according to
      the experimental conditions. In general, the internal reference genes EIF
      (Eukaryotic initiation factor 4A), TBP1 (TATA binding protein 1) and TBP2 (TATA
      binding protein 2) genes had a good performance under most experimental
      conditions, whereas the most widely present used reference genes, ACTIN (Actin
      2), 18S rRNA (18S ribosomal RNA) and GAPDH (Glyceraldehyde-3-phosphate
      dehydrogenase) were not suitable in many experimental conditions. In addition,
      two commonly used programs, geNorm and Normfinder, were proved sufficient for the
      validation. This work provides the first systematic analysis for the selection of
      superior reference genes for accurate transcript normalization in papaya under
      different experimental conditions.

PMID- 22952973
TI  - Subject-specific tendon-aponeurosis definition in Hill-type model predicts higher
      muscle forces in dynamic tasks.
AB  - Neuromusculoskeletal models are a common method to estimate muscle forces.
      Developing accurate neuromusculoskeletal models is a challenging task due to the
      complexity of the system and large inter-subject variability. The estimation of
      muscles force is based on the mechanical properties of tendon-aponeurosis
      complex. Most neuromusculoskeletal models use a generic definition of the tendon
      aponeurosis complex based on in vitro test, perhaps limiting their validity.
      Ultrasonography allows subject-specific estimates of the tendon-aponeurosis
      complex's mechanical properties. The aim of this study was to investigate the
      influence of subject-specific mechanical properties of the tendon-aponeurosis
      complex on a neuromusculoskeletal model of the ankle joint. Seven subjects
      performed isometric contractions from which the tendon-aponeurosis force-strain
      relationship was estimated. Hopping and running tasks were performed and muscle
      forces were estimated using subject-specific tendon-aponeurosis and generic
      tendon properties. Two ultrasound probes positioned over the muscle-tendon
      junction and the mid-belly were combined with motion capture to estimate the in
      vivo tendon and aponeurosis strain of the medial head of gastrocnemius muscle.
      The tendon-aponeurosis force-strain relationship was scaled for the other ankle
      muscles based on tendon and aponeurosis length of each muscle measured by
      ultrasonography. The EMG-driven model was calibrated twice - using the generic
      tendon definition and a subject-specific tendon-aponeurosis force-strain
      definition. The use of subject-specific tendon-aponeurosis definition leads to a
      higher muscle force estimate for the soleus muscle and the plantar-flexor group,
      and to a better model prediction of the ankle joint moment compared to the model
      estimate which used a generic definition. Furthermore, the subject-specific
      tendon-aponeurosis definition leads to a decoupling behaviour between the muscle
      fibre and muscle-tendon unit in agreement with previous experiments using
      ultrasonography. These results indicate the use of subject-specific tendon
      aponeurosis definitions in a neuromusculoskeletal model produce better agreement
      with measured external loads and more physiological model behaviour.

PMID- 22952974
TI  - RNA-Seq of early-infected poplar leaves by the rust pathogen Melampsora larici
      populina uncovers PtSultr3;5, a fungal-induced host sulfate transporter.
AB  - Biotroph pathogens establish intimate interactions with their hosts that are
      conditioned by the successful secretion of effectors in infected tissues and
      subsequent manipulation of host physiology. The identification of early-expressed
      pathogen effectors and early-modulated host functions is currently a major goal
      to understand the molecular basis of biotrophy. Here, we report the 454
      pyrosequencing transcriptome analysis of early stages of poplar leaf colonization
      by the rust fungus Melampsora larici-populina. Among the 841,301 reads considered
      for analysis, 616,879 and 649 were successfully mapped to Populus trichocarpa and
      M. larici-populina genome sequences, respectively. From a methodological aspect,
      these results indicate that this single approach is not appropriate to saturate
      poplar transcriptome and to follow transcript accumulation of the pathogen. We
      identified 19 pathogen transcripts encoding early-expressed small-secreted
      proteins representing candidate effectors of interest for forthcoming studies.
      Poplar RNA-Seq data were validated by oligoarrays and quantitatively analysed,
      which revealed a highly stable transcriptome with a single transcript encoding a
      sulfate transporter (herein named PtSultr3;5, POPTR_0006s16150) showing a
      dramatic increase upon colonization by either virulent or avirulent M. larici
      populina strains. Perspectives connecting host sulfate transport and biotrophic
      lifestyle are discussed.

PMID- 22952976
TI  - Positive effects of nonnative invasive Phragmites australis on larval bullfrogs.
AB  - BACKGROUND: Nonnative Phragmites australis (common reed) is one of the most
      intensively researched and managed invasive plant species in the United States,
      yet as with many invasive species, our ability to predict, control or understand
      the consequences of invasions is limited. Rapid spread of dense Phragmites
      monocultures has prompted efforts to limit its expansion and remove existing
      stands. Motivation for large-scale Phragmites eradication programs includes
      purported negative impacts on native wildlife, a view based primarily on
      observational results. We took an experimental approach to test this assumption,
      estimating the effects of nonnative Phragmites australis on a native amphibian.
      METHODOLOGY/PRINCIPAL FINDINGS: Concurrent common garden and reciprocal
      transplant field experiments revealed consistently strong positive influences of
      Phragmites on Rana catesbeiana (North American bullfrog) larval performance.
      Decomposing Phragmites litter appears to contribute to the effect.
      CONCLUSIONS/SIGNIFICANCE: Positive effects of Phragmites merit further research,
      particularly in regions where both Phragmites and R. catesbeiana are invasive.
      More broadly, the findings of this study reinforce the importance of experimental
      evaluations of the effects of biological invasion to make informed conservation
      and restoration decisions.

PMID- 22952975
TI  - Social cognition in anorexia nervosa: evidence of preserved theory of mind and
      impaired emotional functioning.
AB  - BACKGROUND: The findings of the few studies that have to date investigated the
      way in which individuals with Anorexia Nervosa (AN) navigate their social
      environment are somewhat contradictory. We undertook this study to shed new light
      on the social-cognitive profile of patients with AN, analysing Theory of Mind and
      emotional functioning. Starting from previous evidence on the role of the
      amygdala in the neurobiology of AN and in the social cognition, we hypothesise
      preserved Theory of Mind and impaired emotional functioning in patients with AN.
      METHODOLOGY: Thirty women diagnosed with AN and thirty-two women matched for
      education and age were involved in the study. Theory of Mind and emotional
      functioning were assessed with a set of validated experimental tasks. A measure
      of perceived social support was also used to test the correlations between this
      dimension and the social-cognitive profile of AN patients. PRINCIPAL FINDINGS:
      The performance of patients with AN is significantly worse than that of healthy
      controls on tasks assessing emotional functioning, whereas patients' performance
      is comparable to that of healthy controls on the Theory of Mind task. Correlation
      analyses showed no relationship between scores on any of the social-cognition
      tasks and either age of onset or duration of illness. A correlation between
      social support and emotional functioning was found. This latter result seems to
      suggest a potential role of social support in the treatment and recovery of AN.
      CONCLUSIONS: The pattern of results followed the experimental hypothesis. They
      may be useful to help us better understand the social-cognitive profile of
      patients with AN and to contribute to the development of effective interventions
      based on the ways in which patients with AN actually perceive their social
      environment.

PMID- 22952977
TI  - CaMKII is essential for the function of the enteric nervous system.
AB  - BACKGROUND: Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are major
      downstream mediators of neuronal calcium signaling that regulate multiple
      neuronal functions. CaMKII, one of the key CaMKs, plays a significant role in
      mediating cellular responses to external signaling molecules. Although calcium
      signaling plays an essential role in the enteric nervous system (ENS), the role
      of CaMKII in neurogenic intestinal function has not been determined. In this
      study, we investigated the function and expression pattern of CaMKII in the ENS
      across several mammalian species. METHODOLOGY/PRINCIPAL FINDINGS: CaMKII
      expression was characterized by immunofluorescence analyses and Western Blot.
      CaMKII function was examined by intracellular recordings and by assays of colonic
      contractile activity. Immunoreactivity for CaMKII was detected in the ENS of
      guinea pig, mouse, rat and human preparations. In guinea pig ENS, CaMKII
      immunoreactivity was enriched in both nitric oxide synthase (NOS)- and calretinin
      containing myenteric plexus neurons and non-cholinergic secretomotor/vasodilator
      neurons in the submucosal plexus. CaMKII immunoreactivity was also expressed in
      both cholinergic and non-cholinergic neurons in the ENS of mouse, rat and human.
      The selective CaMKII inhibitor, KN-62, suppressed stimulus-evoked purinergic slow
      EPSPs and ATP-induced slow EPSP-like response in guinea pig submucosal plexus,
      suggesting that CaMKII activity is required for some metabotropic synaptic
      transmissions in the ENS. More importantly, KN-62 significantly suppressed
      tetrodotoxin-induced contractile response in mouse colon, which suggests that
      CaMKII activity is a major determinant of the tonic neurogenic inhibition of this
      tissue. CONCLUSION: ENS neurons across multiple mammalian species express CaMKII.
      CaMKII signaling constitutes an important molecular mechanism for controlling
      intestinal motility and secretion by regulating the excitability of musculomotor
      and secretomotor neurons. These findings revealed a fundamental role of CaMKII in
      the ENS and provide clues for the treatment of intestinal dysfunctions.

PMID- 22952978
TI  - Consistency of network modules in resting-state FMRI connectome data.
AB  - At rest, spontaneous brain activity measured by fMRI is summarized by a number of
      distinct resting state networks (RSNs) following similar temporal time courses.
      Such networks have been consistently identified across subjects using spatial ICA
      (independent component analysis). Moreover, graph theory-based network analyses
      have also been applied to resting-state fMRI data, identifying similar RSNs,
      although typically at a coarser spatial resolution. In this work, we examined
      resting-state fMRI networks from 194 subjects at a voxel-level resolution, and
      examined the consistency of RSNs across subjects using a metric called scaled
      inclusivity (SI), which summarizes consistency of modular partitions across
      networks. Our SI analyses indicated that some RSNs are robust across subjects,
      comparable to the corresponding RSNs identified by ICA. We also found that some
      commonly reported RSNs are less consistent across subjects. This is the first
      direct comparison of RSNs between ICAs and graph-based network analyses at a
      comparable resolution.

PMID- 22952979
TI  - Visualisation of sentinel lymph node with indium-based near infrared emitting
      Quantum Dots in a murine metastatic breast cancer model.
AB  - Due to its non-invasiveness, high temporal resolution and lower cost,
      fluorescence imaging is an interesting alternative to the current method (blue
      dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near
      infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this
      purpose; however, their wide application is limited because of the toxicity of
      heavy metals composing the core. Our recent work demonstrated that indium-based
      QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based
      counterparts. In the present study we confirmed the weak toxicity of CuInS(2)/ZnS
      QDs in different in vitro models. Further in vivo studies in healthy mice showed
      that In-based QDs could be visualised in SLN in a few minutes after
      administration with a progressive increase in fluorescence until 8 h. The
      quantity of indium was assessed in selected organs and tissues by inductively
      coupled plasma - mass spectroscopy (ICP-MS) as a function of post-injection time.
      QD levels decrease rapidly at the injection point in the first hours after
      administration with a parallel increase in the lymph nodes and to a lesser extent
      in the liver and spleen. In addition, we observed that 3.5% of the injected
      indium dose was excreted in faeces in the first 4 days, with only trace
      quantities in the urine. Metastatic spread to the lymph nodes may hamper its
      visualisation. Therefore, we further performed non-invasive fluorescence
      measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed
      by immunohistology and molecular techniques and revealed the utmost metastatic
      invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN
      status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN
      tracer.

PMID- 22952980
TI  - Protective efficacy of Newcastle disease virus expressing soluble trimeric
      hemagglutinin against highly pathogenic H5N1 influenza in chickens and mice.
AB  - BACKGROUND: Highly pathogenic avian influenza virus (HPAIV) causes a highly
      contagious often fatal disease in poultry, resulting in significant economic
      losses in the poultry industry. HPAIV H5N1 also poses a major public health
      threat as it can be transmitted directly from infected poultry to humans. One
      effective way to combat avian influenza with pandemic potential is through the
      vaccination of poultry. Several live vaccines based on attenuated Newcastle
      disease virus (NDV) that express influenza hemagglutinin (HA) have been developed
      to protect chickens or mammalian species against HPAIV. However, the zoonotic
      potential of NDV raises safety concerns regarding the use of live NDV
      recombinants, as the incorporation of a heterologous attachment protein may
      result in the generation of NDV with altered tropism and/or pathogenicity.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study we generated recombinant
      NDVs expressing either full length, membrane-anchored HA of the H5 subtype (NDV
      H5) or a soluble trimeric form thereof (NDV-sH5(3)). A single intramuscular
      immunization with NDV-sH5(3) or NDV-H5 fully protected chickens against disease
      after a lethal challenge with H5N1 and reduced levels of virus shedding in
      tracheal and cloacal swabs. NDV-sH5(3) was less protective than NDV-H5 (50% vs
      80% protection) when administered via the respiratory tract. The NDV-sH5(3) was
      ineffective in mice, regardless of whether administered oculonasally or
      intramuscularly. In this species, NDV-H5 induced protective immunity against
      HPAIV H5N1, but only after oculonasal administration, despite the poor H5
      specific serum antibody response it elicited. CONCLUSIONS/SIGNIFICANCE: Although
      NDV expressing membrane anchored H5 in general provided better protection than
      its counterpart expressing soluble H5, chickens could be fully protected against
      a lethal challenge with H5N1 by using the latter NDV vector. This study thus
      provides proof of concept for the use of recombinant vector vaccines expressing a
      soluble form of a heterologous viral membrane protein. Such vectors may be
      advantageous as they preclude the incorporation of heterologous membrane proteins
      into the viral vector particles.

PMID- 22952981
TI  - Using bioassays and species sensitivity distributions to assess herbicide
      toxicity towards benthic diatoms.
AB  - Although benthic diatoms are widely used in ecological studies of aquatic
      systems, there is still a dearth of data concerning species sensitivities towards
      several contaminants. Within the same community, different species may respond
      differently depending on their physiological and ecological characteristics. This
      lack of knowledge makes specific appropriate risk assessment impossible. To find
      out whether species sensitivity distribution (SSD) could be used to estimate the
      risk of herbicide toxicity for diatoms, we need to know whether their sensitivity
      depends on their physiological and ecological characteristics. We carried out
      single-species bioassays on 11 diatom species exposed to 8 herbicides. Dose
      responses relationships were used to extrapolate the Effective Concentration 5
      (EC(5)) and the Effective Concentration 50 (EC(50)) for each exposure. These data
      were used to fit a SSD curve for each herbicide, and to determine the Hazardous
      concentration 5 (HC(5)) and 50 (HC(50)). Our results revealed a high level of
      variability of the sensitivity in the set of species tested. For photosystem-II
      inhibitor (PSII) herbicides, diatoms species displayed a typical grouping of
      sensitivity levels consistent with their trophic mode and their ecological guild.
      N-heterotroph and "motile" guild species were more tolerant of PSII inhibitors,
      while N-autotroph and "low profile" guild species were more sensitive.
      Comprehensive SSD curves were obtained for 5 herbicides, but not for sulfonylurea
      herbicides or for dimetachlor, which had toxicity levels that were below the
      range of concentration tested. The SSD curves provided the following ranking of
      toxicity: diuron> terbutryn> isoproturon> atrazine> metolachlor. The HC that
      affected 5% of the species revealed that, even at the usual environmental
      concentrations of herbicides, diatom assemblages could be affected, especially by
      isoproturon, terbutryn, and diuron.

PMID- 22952982
TI  - N-terminal region of gelsolin induces apoptosis of activated hepatic stellate
      cells by a caspase-dependent mechanism.
AB  - Activated hepatic stellate cells (HSCs) are the major source for alteration of
      extracellular matrix in fibrosis and cirrhosis. Conditioned medium (CM) collected
      from immortalized human hepatocytes (IHH) have earlier been shown to be
      responsible for apoptosis of HSCs. In this study, we have shown that antibodies
      raised against a peptide derived from a linear B-cell epitope in the N-terminal
      region of gelsolin identified a gelsolin fragment in IHH CM. Analysis of
      activated stellate cell death by CM collected from Huh7 cells transfected with
      plasmids encoding gelsolin deletion mutants suggested that the N-terminal half of
      gelsolin contained sequences which were responsible for stellate cell death.
      Further analysis determined that this activity was restricted to a region
      encompassing amino acids 1-70 in the gelsolin sequence; antibody directed to an
      epitope within this region was able to neutralize stellate cell death. Gelsolin
      modulation of cell death using this fragment involved upregulation of TRAIL-R1
      and TRAIL-R2, and involved caspase 3 activation by extrinsic pathway. The
      apoptotic activity of N-terminal gelsolin fragments was restricted to activated
      but not quiescent stellate cells indicating its potential application in
      therapeutic use as an anti-fibrotic agent. Gelsolin fragments encompassing N
      terminal regions in polypeptides of different molecular sizes were detected by N
      terminal peptide specific antiserum in IHH CM immunoprecipitated with chronically
      HCV infected patient sera, suggesting the presence of autoantibodies generated
      against N-terminal gelsolin fragments in patients with chronic liver disease.

PMID- 22952983
TI  - The tonoplast-localized sucrose transporter in Populus (PtaSUT4) regulates whole
      plant water relations, responses to water stress, and photosynthesis.
AB  - The Populus sucrose (Suc) transporter 4 (PtaSUT4), like its orthologs in other
      plant taxa, is tonoplast localized and thought to mediate Suc export from the
      vacuole into the cytosol. In source leaves of Populus, SUT4 is the predominantly
      expressed gene family member, with transcript levels several times higher than
      those of plasma membrane SUTs. A hypothesis is advanced that SUT4-mediated
      tonoplast sucrose fluxes contribute to the regulation of osmotic gradients
      between cellular compartments, with the potential to mediate both sink
      provisioning and drought tolerance in Populus. Here, we describe the effects of
      PtaSUT4-RNA interference (RNAi) on sucrose levels and raffinose family
      oligosaccharides (RFO) induction, photosynthesis, and water uptake, retention and
      loss during acute and chronic drought stresses. Under normal water-replete
      growing conditions, SUT4-RNAi plants had generally higher shoot water contents
      than wild-type plants. In response to soil drying during a short-term, acute
      drought, RNAi plants exhibited reduced rates of water uptake and delayed wilting
      relative to wild-type plants. SUT4-RNAi plants had larger leaf areas and lower
      photosynthesis rates than wild-type plants under well-watered, but not under
      chronic water-limiting conditions. Moreover, the magnitude of shoot water
      content, height growth, and photosynthesis responses to contrasting soil moisture
      regimes was greater in RNAi than wild-type plants. The concentrations of stress
      responsive RFOs increased in wild-type plants but were unaffected in SUT4-RNAi
      plants under chronically dry conditions. We discuss a model in which the
      subcellular compartmentalization of sucrose mediated by PtaSUT4 is regulated in
      response to both sink demand and plant water status in Populus.

PMID- 22952985
TI  - Pseudoabsence generation strategies for species distribution models.
AB  - BACKGROUND: Species distribution models require selection of species, study
      extent and spatial unit, statistical methods, variables, and assessment metrics.
      If absence data are not available, another important consideration is
      pseudoabsence generation. Different strategies for pseudoabsence generation can
      produce varying spatial representation of species. METHODOLOGY: We considered
      model outcomes from four different strategies for generating pseudoabsences. We
      generating pseudoabsences randomly by 1) selection from the entire study extent,
      2) a two-step process of selection first from the entire study extent, followed
      by selection for pseudoabsences from areas with predicted probability <25%, 3)
      selection from plots surveyed without detection of species presence, 4) a two
      step process of selection first for pseudoabsences from plots surveyed without
      detection of species presence, followed by selection for pseudoabsences from the
      areas with predicted probability <25%. We used Random Forests as our statistical
      method and sixteen predictor variables to model tree species with at least 150
      records from Forest Inventory and Analysis surveys in the Laurentian Mixed Forest
      province of Minnesota. CONCLUSIONS: Pseudoabsence generation strategy completely
      affected the area predicted as present for species distribution models and may be
      one of the most influential determinants of models. All the pseudoabsence
      strategies produced mean AUC values of at least 0.87. More importantly than
      accuracy metrics, the two-step strategies over-predicted species presence, due to
      too much environmental distance between the pseudoabsences and recorded
      presences, whereas models based on random pseudoabsences under-predicted species
      presence, due to too little environmental distance between the pseudoabsences and
      recorded presences. Models using pseudoabsences from surveyed plots produced a
      balance between areas with high and low predicted probabilities and the strongest
      relationship between density and area with predicted probabilities >=75%. Because
      of imperfect accuracy assessment, the best assessment currently may be evaluation
      of whether the species has been sufficiently but not excessively predicted to
      occur.

PMID- 22952984
TI  - Photo-oxidation products of skin surface squalene mediate metabolic and
      inflammatory responses to solar UV in human keratinocytes.
AB  - The study aimed to identify endogenous lipid mediators of metabolic and
      inflammatory responses of human keratinocytes to solar UV irradiation.
      Physiologically relevant doses of solar simulated UVA+UVB were applied to human
      skin surface lipids (SSL) or to primary cultures of normal human epidermal
      keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components,
      alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products
      of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated
      SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time
      dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK
      were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4
      HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2
      b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic
      for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream
      CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV
      markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of
      metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR,
      EGFR, and G-protein-coupled arachidonic acid receptor (G2A).
      CONCLUSIONS/SIGNIFICANCE: Our findings indicate that Sq could be a primary sensor
      of solar UV irradiation in human SSL, and products of its photo-oxidation
      mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB,
      which could be relevant for skin inflammation in the sun-exposed oily skin.

PMID- 22952986
TI  - Periostin directly and indirectly promotes tumor lymphangiogenesis of head and
      neck cancer.
AB  - BACKGROUND: Metastasis to regional lymph nodes via lymphatic vessels plays a key
      role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic
      metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical
      activator of tumor lymphangiogenesis during the process of metastasis. We
      previously identified periostin as an invasion- and angiogenesis-promoting factor
      in head and neck squamous cell carcinoma (HNSCC). In this study, we discovered a
      novel role for periostin in tumor lymphangiogenesis. METHODS AND FINDINGS:
      Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By
      using conditioned media from periostin-overexpressing HNSCC cells, we examined
      tube formation of lymphatic endothelial cells. Conditioned media from periostin
      overexpressing cells promoted tube formation. To know the correlation between
      periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in
      54 HNSCC cases by immunohistochemistry. Periostin expression was correlated well
      with VEGF-C expression in HNSCC cases. Moreover, correlation between periostin
      and VEGF-C secretion was observed in serum from HNSCC patients. Interestingly,
      periostin itself promoted tube formation of lymphatic endothelial cells
      independently of VEGF-C. Periostin-promoted lymphangiogenesis was mediated by Src
      and Akt activity. Indeed possible correlation between periostin and lymphatic
      status in periostin-overexpressing xenograft tumors and HNSCC cases was observed.
      CONCLUSIONS: Our findings suggest that periostin itself as well as periostin
      induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that
      periostin may be a marker for prediction of malignant behaviors in HNSCC and a
      potential target for future therapeutic intervention to obstruct tumoral
      lymphatic invasion and lymphangiogenesis in HNSCC patients.

PMID- 22952987
TI  - The protein precursors of peptides that affect the mechanics of connective tissue
      and/or muscle in the echinoderm Apostichopus japonicus.
AB  - Peptides that cause muscle relaxation or contraction or that modulate
      electrically-induced muscle contraction have been discovered in the sea cucumber
      Apostichopus japonicus (Phylum Echinodermata; Class Holothuroidea). By analysing
      transcriptome sequence data, here the protein precursors of six of these
      myoactive peptides (the SALMFamides Sticho-MFamide-1 and -2, NGIWYamide,
      stichopin, GN-19 and GLRFA) have been identified, providing novel insights on
      neuropeptide and endocrine-type signalling systems in echinoderms. The A.
      japonicus SALMFamide precursor comprises eight putative neuropeptides including
      both L-type and F-type SALMFamides, which contrasts with previous findings from
      the sea urchin Strongylocentrotus purpuratus where L-type and F-type SALMFamides
      are encoded by different genes. The NGIWYamide precursor contains five copies of
      NGIWYamide but, unlike other NG peptide-type neuropeptide precursors in
      deuterostomian invertebrates, the NGIWYamide precursor does not have a C-terminal
      neurophysin domain, indicating loss of this character in holothurians. NGIWYamide
      was originally discovered as a muscle contractant, but it also causes stiffening
      of mutable connective tissue in the body wall of A. japonicus, whilst holokinins
      (PLGYMFR and derivative peptides) cause softening of the body wall. However, the
      mechanisms by which these peptides affect the stiffness of body wall connective
      tissue are unknown. Interestingly, analysis of the A. japonicus transcriptome
      reveals that the only protein containing the holokinin sequence PLGYMFR is an
      alpha-5 type collagen. This suggests that proteolysis of collagen may generate
      peptides (holokinins) that affect body wall stiffness in sea cucumbers, providing
      a novel perspective on mechanisms of mutable connective tissue in echinoderms.

PMID- 22952988
TI  - Potentiation of NMDA receptor-dependent cell responses by extracellular high
      mobility group box 1 protein.
AB  - BACKGROUND: Extracellular high mobility group box 1 (HMGB1) protein can operate
      in a synergistic fashion with different signal molecules promoting an increase of
      cell Ca(2+) influx. However, the mechanisms responsible for this effect of HMGB1
      are still unknown. PRINCIPAL FINDINGS: Here we demonstrate that, at
      concentrations of agonist per se ineffective, HMGB1 potentiates the activation of
      the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR) in isolated
      hippocampal nerve terminals and in a neuroblastoma cell line. This effect was
      abolished by the NMDA channel blocker MK-801. The HMGB1-facilitated NMDAR opening
      was followed by activation of the Ca(2+)-dependent enzymes calpain and nitric
      oxide synthase in neuroblastoma cells, resulting in an increased production of
      NO, a consequent enhanced cell motility, and onset of morphological
      differentiation. We have also identified NMDAR as the mediator of HMGB1
      stimulated murine erythroleukemia cell differentiation, induced by
      hexamethylenebisacetamide. The potentiation of NMDAR activation involved a
      peptide of HMGB1 located in the B box at the amino acids 130-139. This HMGB1
      fragment did not overlap with binding sites for other cell surface receptors of
      HMGB1, such as the advanced glycation end products or the Toll-like receptor 4.
      Moreover, in a competition assay, the HMGB1((130-139)) peptide displaced the
      NMDAR/HMGB1 interaction, suggesting that it comprised the molecular and
      functional site of HMGB1 regulating the NMDA receptor complex. CONCLUSION: We
      propose that the multifunctional cytokine-like molecule HMGB1 released by
      activated, stressed, and damaged or necrotic cells can facilitate NMDAR-mediated
      cell responses, both in the central nervous system and in peripheral tissues,
      independently of other known cell surface receptors for HMGB1.

PMID- 22952989
TI  - Health related quality of life in patients with type 2 diabetes mellitus in Iran:
      a national survey.
AB  - INTRODUCTION: The aim of this study was to measure health-related quality of life
      (HRQoL) in Iranian people with Type 2 Diabetes Mellitus using two different
      measures and examines which socio-demographic and diabetes-related
      characteristics are associated with better quality of life based on a nationally
      distributed sample. METHODS: A multi-stage cluster sampling method was used to
      select 3472 subjects as a part of Iranian surveillance of risk factors of non
      communicable disease (ISRFNCD). EuroQol-5 Dimensions questionnaire (EQ-5D) and
      Visual Analog Scale (VAS) were employed to measure HRQoL. Binary logistic and
      Tobit regression models were used to investigate factors associated with EQ-5D
      results. RESULTS: The mean age of subjects was 59.4 years (SD = 11.7), 61.3% were
      female and had 8.08 years (SD = 6.7) known duration of diabetes. The patients
      reported "some or extreme problems" most frequently in Pain/Discomfort (69.3%)
      and Anxiety/Depression (56.6%) dimensions of EQ-5D. The mean EQ-5D and VAS score
      were 0.70 (95% CI 0.69-0.71) and 56.8 (95% CI 56.15-57.5) respectively. Female
      gender, lower education, unemployment, long duration of diabetes, diabetes
      related hospitalization in past years and having nephropathy and lower extremity
      lesions were associated with higher probabilities of reporting "some or extreme
      problems" in most dimensions of EQ-5D in binary logistic regression models. The
      same factors in addition to retinopathy were significantly associated with lower
      levels of HRQoL in Tobit regression analysis too. CONCLUSIONS: The study findings
      indicate that patients with diabetes in Iran suffer from relatively poor HRQoL.
      Therefore much more attention should be paid to main determinants of HRQoL to
      identify and implement appropriate policies for achieving better management of
      diabetes and ultimately improving the quality of life of diabetic patients in
      this region.

PMID- 22952990
TI  - Decoding lifespan changes of the human brain using resting-state functional
      connectivity MRI.
AB  - The development of large-scale functional brain networks is a complex, lifelong
      process that can be investigated using resting-state functional connectivity MRI
      (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the
      whole-brain functional network in seven decades (8-79 years) of the human
      lifespan. We first used parametric curve fitting to examine linear and nonlinear
      age effect on the resting human brain, and then combined manifold learning and
      support vector machine methods to predict individuals' "brain ages" from rs-fcMRI
      data. We found that age-related changes in interregional functional connectivity
      exhibited spatially and temporally specific patterns. During brain development
      from childhood to senescence, functional connections tended to linearly increase
      in the emotion system and decrease in the sensorimotor system; while quadratic
      trajectories were observed in functional connections related to higher-order
      cognitive functions. The complex patterns of age effect on the whole-brain
      functional network could be effectively represented by a low-dimensional,
      nonlinear manifold embedded in the functional connectivity space, which uncovered
      the inherent structure of brain maturation and aging. Regression of manifold
      coordinates with age further showed that the manifold representation extracted
      sufficient information from rs-fcMRI data to make prediction about individual
      brains' functional development levels. Our study not only gives insights into the
      neural substrates that underlie behavioral and cognitive changes over age, but
      also provides a possible way to quantitatively describe the typical and atypical
      developmental progression of human brain function using rs-fcMRI.

PMID- 22952991
TI  - miR-421 and miR-30c inhibit SERPINE 1 gene expression in human endothelial cells.
AB  - In this work, we assessed whether SERPINE1 expression could be under the
      influence of microRNAs (miRNAs) predicted to bind the SERPINE1 3'UTR region. We
      specifically focused on the 3'UTR region harboring a common polymorphism,
      rs1050955, that have been found associated to SERPINE1 monocyte expression, and
      investigated whether the presence of different alleles at rs1050955 could modify
      the miRNAs binding efficiency and affect PAI-1 protein levels. We demonstrated
      that, in human umbilical vein endothelial cells, both miR-421 and miR-30c
      directly interacted with PAI-1 mRNA to inhibit the expression of the associated
      protein. However, these inhibitory mechanisms were independent on the allele
      present at the rs1050955 locus. We further showed that miR-421 levels correlated
      with PAI-1 activity in the plasma sample of 40 patients with venous thrombosis.
      Our results strongly suggest that the regulation of PAI-1 molecule could be under
      the influence of several miRNAs whose measurement in the plasma of patients could
      be envisaged as a biomarker for inflammatory and thrombotic disorders.

PMID- 22952992
TI  - Listening to women's voices: the quality of care of women experiencing severe
      maternal morbidity, in Accra, Ghana.
AB  - BACKGROUND: Women who survive severe obstetric complications can provide insight
      into risk factors and potential strategies for prevention of maternal morbidity
      as well as maternal mortality. We interviewed 32 women, in an urban facility in
      Ghana, who had experienced severe morbidity defined using a standardized WHO near
      miss definition and identification criteria. Women provided personal accounts of
      their experiences of severe maternal morbidity and perceptions of the care they
      received. METHODS AND FINDINGS: The study took place in a referral facility in
      urban Accra, and semi-structured interviews were conducted with women who had
      either a maternal near miss (n = 17) or a potentially life-threatening
      complication (n = 15). The most common themes surrounding the traumatic delivery
      were the fear of dying and concern over the potential (or actual) loss of the
      baby. For many women, the loss of a baby negatively influenced how they viewed
      and coped with this experience. Women's perceptions of the quality of the care
      highlighted several key factors such as the importance of information, good
      communication and attitudes, and availability of human (i.e., more doctors) and
      physical resources (i.e., more beds, water) at the facility. CONCLUSIONS: Our
      results suggest that experiences of women with severe maternal morbidity may
      inform different aspects of quality improvement in the facilities, which in turn
      have a positive impact on future health seeking behavior, service utilization and
      reduction in maternal morbidity and mortality.

PMID- 22952993
TI  - Transitory versus persistent effects of connectivity in environmentally
      homogeneous metacommunities.
AB  - While the effect of habitat connectivity on local and regional diversity has been
      analysed in a number of studies, time-dependent dynamics in metacommunities have
      received comparatively little consideration. When local patches of a
      metacommunity are identical in environmental conditions but differ in initial
      community composition, dispersal among patches may result in homogenization of
      local communities. In a microcosm experiment with benthic ciliates, we tested the
      hypothesis that the effect of connectivity on diversity is time-dependent and
      only transitory, with the degree of connectivity affecting the time to
      homogenization but not the final outcome. Six microcosms were connected to a
      metacommunity with one of three levels of connectivity. The six patches differed
      in initial community composition but were identical in environmental conditions.
      We found a time-dependent and transitory effect of connectivity on local and
      regional richness and on local Shannon diversity, while Bray-Curtis dissimilarity
      and regional Shannon diversity were persistently affected by connectivity. Local
      richness increased and regional richness decreased with connectivity during the
      initial phase of the experiment but soon converged to similar values in all three
      connectivity treatments. Local Shannon diversity was unimodally related to time,
      with maximum diversity reached sooner with high than with medium or low
      connectivity. Eventually, however, local diversity converged to similar values
      irrespective of connectivity. At the regional scale, Shannon diversity was
      persistently lower with high than with low connectivity. While initial
      differences in community composition vanished with medium and high connectivity,
      they were maintained with low connectivity resulting in persistently high beta
      and regional diversity. The effect of connectivity on ciliate community
      composition translated down to the algal resource, as stronger dominance of the
      superior competitor with high and medium connectivity resulted in stronger
      depletion of the resource.

PMID- 22952994
TI  - BMS309403 stimulates glucose uptake in myotubes through activation of AMP
      activated protein kinase.
AB  - BMS309403 is a biphenyl azole inhibitor against fatty acid binding protein 4
      (FABP4) and regarded as a lead compound for effective treatment of obesity
      related cardio-metabolic diseases. Here we discovered an off-target activity of
      BMS309403 in that it stimulates glucose uptake in C2C12 myotubes in a temporal
      and dose dependent manner via activation of AMP-activated protein kinase (AMPK)
      signaling pathway but independent of FABPs. Further analysis indicated that
      BMS309403 activates AMPK through increasing the ratio of intracellular AMP:ATP
      while decreasing mitochondrial membrane potential. These findings provide
      mechanistic insights on the action of BMS309403.

PMID- 22952995
TI  - Cholera outbreak in Senegal in 2005: was climate a factor?
AB  - Cholera is an acute diarrheal illness caused by Vibrio cholerae and occurs as
      widespread epidemics in Africa. In 2005, there were 31,719 cholera cases, with
      458 deaths in the Republic of Senegal. We retrospectively investigated the
      climate origin of the devastating floods in mid-August 2005, in the Dakar Region
      of Senegal and the subsequent outbreak of cholera along with the pattern of
      cholera outbreaks in three other regions of that country. We compared rainfall
      patterns between 2002 and 2005 and the relationship between the sea surface
      temperature (SST) gradient in the tropical Atlantic Ocean and precipitation over
      Senegal for 2005. Results showed a specific pattern of rainfall throughout the
      Dakar region during August, 2005, and the associated rainfall anomaly coincided
      with an exacerbation of the cholera epidemic. Comparison of rainfall and
      epidemiological patterns revealed that the temporal dynamics of precipitation,
      which was abrupt and heavy, was presumably the determining factor. Analysis of
      the SST gradient showed that the Atlantic Ocean SST variability in 2005 differed
      from that of 2002 to 2004, a result of a prominent Atlantic meridional mode. The
      influence of this intense precipitation on cholera transmission over a densely
      populated and crowded region was detectable for both Dakar and Thies, Senegal.
      Thus, high resolution rainfall forecasts at subseasonal time scales should
      provide a way forward for an early warning system in Africa for cholera and,
      thereby, trigger epidemic preparedness. Clearly, attention must be paid to both
      natural and human induced environmental factors to devise appropriate action to
      prevent cholera and other waterborne disease epidemics in the region.

PMID- 22952996
TI  - Ergosterol peroxide isolated from Ganoderma lucidum abolishes microRNA miR-378
      mediated tumor cells on chemoresistance.
AB  - Due to an altered expression of oncogenic factors and tumor suppressors,
      aggressive cancer cells have an intrinsic or acquired resistance to
      chemotherapeutic agents. This typically contributes to cancer recurrence after
      chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell
      self-renewal and cancer development. Here we report that tumor cells transfected
      with miR-378 acquired properties of aggressive cancer cells. Overexpression of
      miR-378 enhanced both cell survival and colony formation, and contributed to
      multiple drug resistance. Higher concentrations of chemotherapeutic drugs were
      needed to induce death of miR-378-transfected cells than to induce death of
      control cells. We found that the biologically active component isolated from
      Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We
      purified and identified the biologically active component of Ganoderma lucidum as
      ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater
      activity in inducing death of miR-378 cells than the GFP cells. Lower
      concentrations of ergosterol peroxide were needed to induce death of the miR-378
      transfected cells than in the control cells. With further clinical development,
      ergosterol peroxide represents a promising new reagent that can overcome the drug
      resistance of tumor cells.

PMID- 22952998
TI  - Artificial neural networks based controller for glucose monitoring during clamp
      test.
AB  - Insulin resistance (IR) is one of the most widespread health problems in modern
      times. The gold standard for quantification of IR is the hyperinsulinemic
      euglycemic glucose clamp technique. During the test, a regulated glucose infusion
      is delivered intravenously to maintain a constant blood glucose concentration.
      Current control algorithms for regulating this glucose infusion are based on
      feedback control. These models require frequent sampling of blood, and can only
      partly capture the complexity associated with regulation of glucose. Here we
      present an improved clamp control algorithm which is motivated by the stochastic
      nature of glucose kinetics, while using the minimal need in blood samples
      required for evaluation of IR. A glucose pump control algorithm, based on
      artificial neural networks model was developed. The system was trained with a
      data base collected from 62 rat model experiments, using a back-propagation
      Levenberg-Marquardt optimization. Genetic algorithm was used to optimize network
      topology and learning features. The predictive value of the proposed algorithm
      during the temporal period of interest was significantly improved relative to a
      feedback control applied at an equivalent low sampling interval. Robustness to
      noise analysis demonstrates the applicability of the algorithm in realistic
      situations.

PMID- 22952999
TI  - Effect of ambient temperature on the thermoregulatory and locomotor stimulant
      effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats.
AB  - The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, "plant food",
      "bath salts") is a recent addition to the list of popular recreational
      psychomotor-stimulant compounds. Relatively little information about this drug is
      available in the scientific literature, but popular media reports have driven
      recent drug control actions in the UK and several US States. Online user reports
      of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy")
      prompted the current investigation of the thermoregulatory and locomotor effects
      of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous
      administration of 4-MMC (1-10 mg/kg ) using an implantable radiotelemetry system
      under conditions of low (23 degrees C) and high (27 degrees C) ambient
      temperature. A reliable reduction of body temperature was produced by 4-MMC in
      Wistar rats at 23 degrees C or 27 degrees C with only minimal effect in Sprague
      Dawley rats. Increased locomotor activity was observed after 4-MMC administration
      in both strains with significantly more activity produced in the Sprague-Dawley
      strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular
      serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies
      confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was
      nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain.
      Furthermore, hypothermia produced by the serotonin 1(A/7) receptor agonist 8
      hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain.
      These results show that the cathinone analog 4-MMC exhibits thermoregulatory and
      locomotor properties that are distinct from those established for methamphetamine
      or MDMA in prior work, despite recent evidence of neuropharmacological similarity
      with MDMA.

PMID- 22952997
TI  - Analysis of the transcriptomes downstream of Eyeless and the Hedgehog,
      Decapentaplegic and Notch signaling pathways in Drosophila melanogaster.
AB  - Tissue-specific transcription factors are thought to cooperate with signaling
      pathways to promote patterned tissue specification, in part by co-regulating
      transcription. The Drosophila melanogaster Pax6 homolog Eyeless forms a complex,
      incompletely understood regulatory network with the Hedgehog, Decapentaplegic and
      Notch signaling pathways to control eye-specific gene expression. We report a
      combinatorial approach, including mRNAseq and microarray analyses, to identify
      targets co-regulated by Eyeless and Hedgehog, Decapentaplegic or Notch. Multiple
      analyses suggest that the transcriptomes resulting from co-misexpression of
      Eyeless+signaling factors provide a more complete picture of eye development
      compared to previous efforts involving Eyeless alone: (1) Principal components
      analysis and two-way hierarchical clustering revealed that the Eyeless+signaling
      factor transcriptomes are closer to the eye control transcriptome than when
      Eyeless is misexpressed alone; (2) more genes are upregulated at least three-fold
      in response to Eyeless+signaling factors compared to Eyeless alone; (3) based on
      gene ontology analysis, the genes upregulated in response to Eyeless+signaling
      factors had a greater diversity of functions compared to Eyeless alone. Through a
      secondary screen that utilized RNA interference, we show that the predicted gene
      CG4721 has a role in eye development. CG4721 encodes a neprilysin family
      metalloprotease that is highly up-regulated in response to Eyeless+Notch,
      confirming the validity of our approach. Given the similarity between D.
      melanogaster and vertebrate eye development, the large number of novel genes
      identified as potential targets of Ey+signaling factors will provide novel
      insights to our understanding of eye development in D. melanogaster and humans.

PMID- 22953000
TI  - Recruitment of Rpd3 to the telomere depends on the protein arginine
      methyltransferase Hmt1.
AB  - In the yeast Saccharomyces cerevisiae, the establishment and maintenance of
      silent chromatin at the telomere requires a delicate balance between opposing
      activities of histone modifying enzymes. Previously, we demonstrated that the
      protein arginine methyltransferase Hmt1 plays a role in the formation of yeast
      silent chromatin. To better understand the nature of the Hmt1 interactions that
      contribute to this phenomenon, we carried out a systematic reverse genetic screen
      using a null allele of HMT1 and the synthetic genetic array (SGA) methodology.
      This screen revealed interactions between HMT1 and genes encoding components of
      the histone deacetylase complex Rpd3L (large). A double mutant carrying both RPD3
      and HMT1 deletions display increased telomeric silencing and Sir2 occupancy at
      the telomeric boundary regions, when comparing to a single mutant carrying Hmt1
      deletion only. However, the dual rpd3/hmt1-null mutant behaves like the rpd3-null
      single mutant with respect to silencing behavior, indicating that RPD3 is
      epistatic to HMT1. Mutants lacking either Hmt1 or its catalytic activity display
      an increase in the recruitment of histone deacetylase Rpd3 to the telomeric
      boundary regions. Moreover, in such loss-of-function mutants the levels of
      acetylated H4K5, which is a substrate of Rpd3, are altered at the telomeric
      boundary regions. In contrast, the level of acetylated H4K16, a target of the
      histone deacetylase Sir2, was increased in these regions. Interestingly, mutants
      lacking either Rpd3 or Sir2 display various levels of reduction in dimethylated
      H4R3 at these telomeric boundary regions. Together, these data provide insight
      into the mechanism whereby Hmt1 promotes the proper establishment and maintenance
      of silent chromatin at the telomeres.

PMID- 22953001
TI  - Impaired virus clearance, compromised immune response and increased mortality in
      type 2 diabetic mice infected with West Nile virus.
AB  - Clinicoepidemiological data suggest that type 2 diabetes is associated with
      increased risk of West Nile virus encephalitis (WNVE). However, no experimental
      studies have elucidated the role of diabetes in WNV neuropathogenesis. Herein, we
      employed the db/db mouse model to understand WNV immunopathogenesis in diabetics.
      Nine-week old C57BL/6 WT and db/db mice were inoculated with WNV and mortality,
      virus burden in the periphery and brain, and antiviral defense responses were
      analyzed. db/db mice were highly susceptible to WNV disease, exhibited increased
      tissue tropism and mortality than the wild-type mice, and were unable to clear
      the infection. Increased and sustained WNV replication was observed in the serum,
      peripheral tissues and brain of db/db mice, and heightened virus replication in
      the periphery was correlated with enhanced neuroinvasion and replication of WNV
      in the brain. WNV infection in db/db mice was associated with enhanced
      inflammatory response and compromised antiviral immune response characterized by
      delayed induction of IFN-alpha, and significantly reduced concentrations of WNV
      specific IgM and IgG antibodies. The compromised immune response in db/db mice
      correlated with increased viremia. These data suggest that delayed immune
      response coupled with failure to clear the virus leads to increased mortality in
      db/db mice. In conclusion, this study provides unique mechanistic insight into
      the immunopathogenesis of WNVE observed in diabetics and can be used to develop
      therapeutics for the management of WNVE among diabetic patients.

PMID- 22953002
TI  - Differential proteomics and functional research following gene therapy in a mouse
      model of Leber congenital amaurosis.
AB  - Leber congenital amaurosis (LCA) is one of the most severe forms of inherited
      retinal degeneration and can be caused by mutations in at least 15 different
      genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal
      degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65
      gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one
      eye, while the contralateral eye served as a control. Proteomics were compared
      between untreated rd12 and normal control retinas on P14 and P21, and among
      treated and untreated rd12 retinas and control retinas on P42. Gene therapy in
      rd12 mice restored retinal function in treated eyes, which was demonstrated by
      electroretinography (ERG). Proteomic analysis successfully identified 39 proteins
      expressed differently among the 3 groups. The expression of 3 proteins involved
      in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock
      protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence,
      Western blot and real-time PCR confirmed the quantitative changes in their
      expression. Furthermore, cell culture studies suggested that peroxiredoxin 6
      could act in an antioxidant role in rd12 mice. Our findings support the
      feasibility of gene therapy in LCA2 patients and support a role for alpha A
      crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic
      mechanisms involved in LCA2 disease process.

PMID- 22953003
TI  - Challenges to licensure of enterovirus 71 vaccines.
AB  - Human enteroviruses usually cause self-limited infections except polioviruses and
      enterovirus 71 (EV71), which frequently involve neurological complications. EV71
      vaccines are being evaluated in humans. However, several challenges to licensure
      of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA)
      are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A
      polyvalent vaccine that can provide protection against EV71 and prevalent CA are
      desirable. Secondly, infants are the target population of HFMD vaccines and it
      would need multi-national efficacy trials to prove clinical protection and speed
      up the licensure and usage of HFMD vaccines in children. An international network
      for enterovirus surveillance and clinical trials is urgently needed. Thirdly,
      EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies
      are warranted to clarify clinical and epidemiological significances of the
      antigenic and genetic variations between different EV71 genogroups, which is
      critical for vaccine design.

PMID- 22953004
TI  - The impact of the US priority review voucher on private-sector investment in
      global health research and development.

PMID- 22953005
TI  - A case of cutaneous tuberculosis in a Buruli ulcer-endemic area.

PMID- 22953006
TI  - Detection of viable Mycobacterium ulcerans in clinical samples by a novel
      combined 16S rRNA reverse transcriptase/IS2404 real-time qPCR assay.

PMID- 22953008
TI  - Obstetric fistula is a "neglected tropical disease".

PMID- 22953007
TI  - Why do people not attend for treatment for trachomatous trichiasis in Ethiopia? A
      study of barriers to surgery.
AB  - BACKGROUND: Trachomatous trichiasis (TT) surgery is provided free or subsidised
      in most trachoma endemic settings. However, only 18-66% of TT patients attend for
      surgery. This study analyses barriers to attendance among TT patients in
      Ethiopia, the country with the highest prevalence of TT in the world.
      METHODOLOGY/PRINCIPAL FINDINGS: Participants with previously un-operated TT were
      recruited at 17 surgical outreach campaigns in Amhara Region, Ethiopia. An
      interview was conducted to ascertain why they had not attended for surgery
      previously. A trachoma eye examination was performed by an ophthalmologist. 2591
      consecutive individuals were interviewed. The most frequently cited barriers to
      previous attendance for surgery were lack of time (45.3%), financial constraints
      (42.9%) and lack of an escort (35.5% in females, 19.6% in males). Women were more
      likely to report a fear of surgery (7.7% vs 3.2%, p<0.001) or be unaware of how
      to access services (4.5% vs 1.0% p<0.001); men were more frequently asymptomatic
      (19.6% vs 10.1%, p<0.001). Women were also less likely to have been previously
      offered TT surgery than men (OR = 0.70, 95%CI 0.53-0.94).
      CONCLUSIONS/SIGNIFICANCE: The major barriers to accessing surgery from the
      patients' perspective are the direct and indirect costs of surgery. These can to
      a large extent be reduced or overcome through the provision of free or low cost
      surgery at the community level. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00522860 and NCT00522912.

PMID- 22953009
TI  - Detection of Giardia duodenalis assemblages A and B in human feces by simple,
      assemblage-specific PCR assays.
AB  - The flagellated protozoan Giardia duodenalis is a common gastrointestinal
      parasite of mammals, including humans. Molecular characterizations have shown the
      existence of eight genetic groups (or assemblages) in the G. duodenalis species
      complex. Human infections are caused by assemblages A and B, which infect other
      mammals as well. Whether transmission routes, animal reservoirs and associations
      with specific symptoms differ for assemblage A and assemblage B is not clear.
      Furthermore, the occurrence and clinical significance of mixed (A+B) infections
      is also poorly understood. To date, the majority of PCR assays has been developed
      to identify all G. duodenalis assemblages based on the use of primers that bind
      to conserved regions, yet a reliable identification of specific assemblages is
      better achieved by ad hoc methods. The aim of this work was to design simple PCR
      assays that, based on the use of assemblage-specific primers, produce diagnostic
      bands of different lengths for assemblage A and B. We first generated novel
      sequence information from assemblage B, identified homologous sequences in the
      assemblage A genome, and designed primers at six independent loci. Experiments
      performed on DNA extracted from axenic cultures showed that two of the six assays
      can detect the equivalent of a single cyst and are not negatively influenced by
      disproportions between DNA of each assemblage, at least up to a 9:1 ratio.
      Further experiments on DNAs extracted from feces showed that the two assays can
      detect both assemblages in single tube reactions with excellent reliability.
      Finally, the robustness of these assays was demonstrated by testing a large
      collection of human isolates previously typed by multi-locus genotyping.

PMID- 22953010
TI  - Common coinfections of Giardia intestinalis and Helicobacter pylori in non
      symptomatic Ugandan children.
AB  - BACKGROUND: The protozoan parasite Giardia intestinalis and the pathogenic
      bacterium Helicobacter pylori are well known for their high prevalences in human
      hosts worldwide. The prevalence of both organisms is known to peak in densely
      populated, low resource settings and children are infected early in life.
      Different Giardia genotypes/assemblages have been associated with different
      symptoms and H. pylori with induction of cancer. Despite this, not much data are
      available from sub-Saharan Africa with regards to the prevalence of different G.
      intestinalis assemblages and their potential association with H. pylori
      infections. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples from 427 apparently
      healthy children, 0-12 years of age, living in urban Kampala, Uganda were
      analyzed for the presence of H. pylori and G. intestinalis. G. intestinalis was
      found in 86 (20.1%) out of the children and children age 1<5 years had the
      highest rates of colonization. H. pylori was found in 189 (44.3%) out of the 427
      children and there was a 3-fold higher risk of concomitant G. intestinalis and H.
      pylori infections compared to non-concomitant G. intestinalis infection, OR = 2.9
      (1.7-4.8). No significant association was found in the studied population with
      regard to the presence of Giardia and gender, type of toilet, source of drinking
      water or type of housing. A panel of 45 G. intestinalis positive samples was
      further analyzed using multi-locus genotyping (MLG) on three loci, combined with
      assemblage-specific analyses. Giardia MLG analysis yielded a total of five
      assemblage AII, 25 assemblage B, and four mixed assemblage infections. The
      assemblage B isolates were highly genetically variable but no significant
      association was found between Giardia assemblage type and H. pylori infection.
      CONCLUSIONS/SIGNIFICANCE: This study shows that Giardia assemblage B dominates in
      children in Kampala, Uganda and that the presence of H. pylori is an associated
      risk factor for G. intestinalis infection.

PMID- 22953011
TI  - The importance of long-term social research in enabling participation and
      developing engagement strategies for new dengue control technologies.
AB  - BACKGROUND: In recent years, new strategies aimed at reducing the capacity of
      mosquito vectors to transmit dengue fever have emerged. As with earlier control
      methods, they will have to be employed in a diverse range of communities across
      the globe and into the main settings for disease transmission, the homes,
      businesses and public buildings of residents in dengue-affected areas. However,
      these strategies are notably different from previous methods and draw on
      technologies that are not without controversy. Public engagement and
      authorization are critical to the future success of these programs.
      METHODOLOGY/PRINCIPAL FINDINGS: This paper reports on an Australian case study
      where long-term social research was used to enable participation and the design
      of an engagement strategy tailored specifically to the sociopolitical setting of
      a potential trial release site of Wolbachia-infected Aedes aegytpi mosquitoes.
      Central themes of the social research, methods used and conclusions drawn are
      briefly described. Results indicate that different communities are likely to have
      divergent expectations, concerns and cultural sensibilities with regard to
      participation, engagement and authorization. CONCLUSIONS/SIGNIFICANCE: The
      findings show that a range of issues need to be understood and taken into account
      to enable sensitive, ethical and effective engagement when seeking public support
      for new dengue control methods.

PMID- 22953012
TI  - Quinolone resistance in absence of selective pressure: the experience of a very
      remote community in the Amazon forest.
AB  - BACKGROUND: Quinolones are potent broad-spectrum bactericidal agents increasingly
      employed also in resource-limited countries. Resistance to quinolones is an
      increasing problem, known to be strongly associated with quinolone exposure. We
      report on the emergence of quinolone resistance in a very remote community in the
      Amazon forest, where quinolones have never been used and quinolone resistance was
      absent in 2002. METHODS: The community exhibited a considerable level of
      geographical isolation, limited contact with the exterior and minimal antibiotic
      use (not including quinolones). In December 2009, fecal carriage of antibiotic
      resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in
      48 animals reared in the community. All fluoroquinolone-resistant isolates were
      genotyped and characterized for the mechanisms of plasmid- and chromosomal
      mediated quinolone resistance. PRINCIPAL FINDINGS: Despite the characteristics of
      the community remained substantially unchanged during the period 2002-2009,
      carriage of quinolone-resistant E. coli was found to be common in 2009 both in
      humans (45% nalidixic acid, 14% ciprofloxacin) and animals (54% nalidixic acid,
      23% ciprofloxacin). Ciprofloxacin-resistant isolates of human and animal origin
      showed multidrug resistance phenotypes, a high level of genetic heterogeneity,
      and a combination of GyrA (Ser83Leu and Asp87Asn) and ParC (Ser80Ile)
      substitutions commonly observed in fluoroquinolone-resistant clinical isolates of
      E. coli. CONCLUSIONS: Remoteness and absence of antibiotic selective pressure did
      not protect the community from the remarkable emergence of quinolone resistance
      in E. coli. Introduction of the resistant strains from antibiotic-exposed
      settings is the most likely source, while persistence and dissemination in the
      absence of quinolone exposure is likely mostly related with poor sanitation.
      Interventions aimed at reducing the spreading of resistant isolates (by improving
      sanitation and water/food safety) are urgently needed to preserve the efficacy of
      quinolones in resource-limited countries, as control strategies based only on
      antibiotic restriction policies are unlikely to succeed in those settings.

PMID- 22953013
TI  - Where, when and why do tsetse contact humans? Answers from studies in a national
      park of Zimbabwe.
AB  - BACKGROUND: Sleeping sickness, also called human African trypanosomiasis, is
      transmitted by the tsetse, a blood-sucking fly confined to sub-Saharan Africa.
      The form of the disease in West and Central Africa is carried mainly by species
      of tsetse that inhabit riverine woodland and feed avidly on humans. In contrast,
      the vectors for the East and Southern African form of the disease are usually
      savannah species that feed mostly on wild and domestic animals and bite humans
      infrequently, mainly because the odours produced by humans can be repellent.
      Hence, it takes a long time to catch many savannah tsetse from people, which in
      turn means that studies of the nature of contact between savannah tsetse and
      humans, and the ways of minimizing it, have been largely neglected.
      METHODOLOGY/PRINCIPAL FINDINGS: The savannah tsetse, Glossina morsitans morsitans
      and G. pallidipes, were caught from men in the Mana Pools National park of
      Zimbabwe. Mostly the catch consisted of young G. m. morsitans, with little food
      reserve. Catches were increased by 4-8 times if the men were walking, not
      stationary, and increased about ten times more if they rode on a truck at 10
      km/h. Catches were unaffected if the men used deodorant or were baited with
      artificial ox odour, but declined by about 95% if the men were with an ox.
      Surprisingly, men pursuing their normal daily activities were bitten about as
      much when in or near buildings as when in woodland. Catches from oxen and a
      standard ox-like trap were poor indices of the number and physiological state of
      tsetse attacking men. CONCLUSION/SIGNIFICANCE: The search for new strategies to
      minimize the contact between humans and savannah tsetse should focus on that
      occurring in buildings and vehicles. There is a need to design a man-like trap to
      help to provide an index of sleeping sickness risk.

PMID- 22953014
TI  - Oral susceptibility of Singapore Aedes (Stegomyia) aegypti (Linnaeus) to Zika
      virus.
AB  - BACKGROUND: Zika virus (ZIKV) is a little known flavivirus that caused a major
      outbreak in 2007, in the South-western Pacific Island of Yap. It causes dengue
      like syndromes but with milder symptoms. In Africa, where it was first isolated,
      ZIKV is mainly transmitted by sylvatic Aedes mosquitoes. The virus has also been
      isolated from Ae. aegypti and it is considered to be the vector involved in the
      urban transmission of the virus. Transmission of the virus by an African strain
      of Ae. aegypti has also been demonstrated under laboratory conditions. The aim of
      the present study is to describe the oral susceptibility of a Singapore strain of
      Ae. aegypti to ZIKV, under conditions that simulate local climate.
      METHODOLOGY/PRINCIPAL FINDINGS: To assess the receptivity of Singapore's Ae.
      aegypti to the virus, we orally exposed a local mosquito strain to a Ugandan
      strain of ZIKV. Upon exposure, fully engorged mosquitoes were maintained in an
      environmental chamber set at 29  degrees C and 70-75% RH. Eight mosquitoes were
      then sampled daily from day 1 to day 7, and subsequently on days 10 and 14 post
      exposure (pe). The virus titer of the midgut and salivary glands of each mosquito
      were determined using a tissue culture infectious dose(50) (TCID(50)) assay. High
      midgut infection and salivary gland dissemination rates were observed. By day 5
      after the infectious blood meal, ZIKV was found in the salivary glands of more
      than half of the mosquitoes tested (62%); and by day 10, all mosquitoes were
      potentially infective. CONCLUSIONS/SIGNIFICANCE: This study showed that
      Singapore's urban Ae. aegypti are susceptible and are potentially capable of
      transmitting ZIKV. The virus could be established in Singapore should it be
      introduced. Nevertheless, Singapore's current dengue control strategy is
      applicable to control ZIKV.

PMID- 22953015
TI  - The "auto-dissemination" approach: a novel concept to fight Aedes albopictus in
      urban areas.
AB  - BACKGROUND: The main constraint to the fight against container-breeding mosquito
      vectors of human arboviruses is the difficulty in targeting the multiplicity of
      larval sources, mostly represented by small man-made water containers. The aim of
      this work is to assess the feasibility of the "auto-dissemination" approach,
      already tested for Aedes aegypti, as a possible alternative to traditional,
      inefficient control tools, against Ae. albopictus in urban areas. The approach is
      based on the possibility that wild adult females, exposed to artificial resting
      sites contaminated with pyriproxyfen, can disseminate this juvenile hormone
      analogue to larval habitats, thus interfering with adult emergence. METHODOLOGY:
      We carried out four field experiments in two areas of Rome that are typically
      highly infested with Ae. albopictus, i.e. the main cemetery and a small green
      area within a highly urbanised neighbourhood. In each area we used 10
      pyriproxyfen "dissemination" stations, 10 "sentinel" sites and 10 covered,
      control sites. The sentinel and control sites each contained 25 Ae. albopictus
      larvae. These were monitored for development and adult emergence. PRINCIPAL
      FINDINGS: When a 5% pyriproxyfen powder was used to contaminate the dissemination
      sites, we observed significantly higher mortality at the pupal stage in the
      sentinel sites (50-70%) than in the controls (<2%), showing that pyriproxyfen was
      transferred by mosquitoes into sentinel sites and that it had a lethal effect.
      CONCLUSIONS: The results support the potential feasibility of the auto
      dissemination approach to control Ae. albopictus in urban areas. Further studies
      will be carried out to optimize the method and provide an effective tool to
      reduce the biting nuisance caused by this aggressive species and the transmission
      risk of diseases such as Dengue and Chikungunya. These arboviruses pose an
      increasing threat in Europe as Ae. albopictus expands its range.

PMID- 22953016
TI  - Global gene expression analysis of the zoonotic parasite Trichinella spiralis
      revealed novel genes in host parasite interaction.
AB  - BACKGROUND: Trichinellosis is a typical food-borne zoonotic disease which is
      epidemic worldwide and the nematode Trichinella spiralis is the main pathogen.
      The life cycle of T. spiralis contains three developmental stages, i.e. adult
      worms, new borne larva (new borne L1 larva) and muscular larva (infective L1
      larva). Stage-specific gene expression in the parasites has been investigated
      with various immunological and cDNA cloning approaches, whereas the genome-wide
      transcriptome and expression features of the parasite have been largely unknown.
      The availability of the genome sequence information of T. spiralis has made it
      possible to deeply dissect parasite biology in association with global gene
      expression and pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: In this study,
      we analyzed the global gene expression patterns in the three developmental stages
      of T. spiralis using digital gene expression (DGE) analysis. Almost 15 million
      sequence tags were generated with the Illumina RNA-seq technology, producing
      expression data for more than 9,000 genes, covering 65% of the genome. The
      transcriptome analysis revealed thousands of differentially expressed genes
      within the genome, and importantly, a panel of genes encoding functional proteins
      associated with parasite invasion and immuno-modulation were identified. More
      than 45% of the genes were found to be transcribed from both strands, indicating
      the importance of RNA-mediated gene regulation in the development of the
      parasite. Further, based on gene ontological analysis, over 3000 genes were
      functionally categorized and biological pathways in the three life cycle stage
      were elucidated. CONCLUSIONS AND SIGNIFICANCE: The global transcriptome of T.
      spiralis in three developmental stages has been profiled, and most gene activity
      in the genome was found to be developmentally regulated. Many metabolic and
      biological pathways have been revealed. The findings of the differential
      expression of several protein families facilitate understanding of the molecular
      mechanisms of parasite biology and the pathological aspects of trichinellosis.

PMID- 22953017
TI  - The interactive roles of Aedes aegypti super-production and human density in
      dengue transmission.
AB  - BACKGROUND: A. aegypti production and human density may vary considerably in
      dengue endemic areas. Understanding how interactions between these factors
      influence the risk of transmission could improve the effectiveness of the
      allocation of vector control resources. To evaluate the combined impacts of
      variation in A. aegypti production and human density we integrated field data
      with simulation modeling. METHODOLOGY/PRINCIPAL FINDINGS: Using data from seven
      censuses of A. aegypti pupae (2007-2009) and from demographic surveys, we
      developed an agent-based transmission model of the dengue transmission cycle
      across houses in 16 dengue-endemic urban 'patches' (1-3 city blocks each) of
      Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only
      5% of houses, defined as super-producers. Average secondary infections (R(0))
      depended on infrequent, but highly explosive transmission events. These super
      spreading events occurred almost exclusively when the introduced infectious
      person infected mosquitoes that were produced in super-productive containers.
      Increased human density favored R(0), and when the likelihood of human
      introduction of virus was incorporated into risk, a strong interaction arose
      between vector production and human density. Simulated intervention of super
      productive containers was substantially more effective in reducing dengue risk at
      higher human densities. SIGNIFICANCE/CONCLUSIONS: These results show significant
      interactions between human population density and the natural regulatory pattern
      of A. aegypti in the dynamics of dengue transmission. The large epidemiological
      significance of super-productive containers suggests that they have the potential
      to influence dengue viral adaptation to mosquitoes. Human population density
      plays a major role in dengue transmission, due to its potential impact on human
      A. aegypti contact, both within a person's home and when visiting others. The
      large variation in population density within typical dengue endemic cities
      suggests that it should be a major consideration in dengue control policy.

PMID- 22953018
TI  - Utilization of ELISA using thioredoxin peroxidase-1 and tandem repeat proteins
      for diagnosis of Schistosoma japonicum infection among water buffaloes.
AB  - BACKGROUND: The presence of animal reservoirs in Schistosoma japonicum infection
      has been a major obstacle in the control of schistosomiasis. Previous studies
      have proven that the inclusion of control measures on animal reservoir hosts for
      schistosomiasis contributed to the decrease of human cases. Animal surveillance
      should therefore be included to strengthen and improve the capabilities of
      current serological tests. METHODOLOGY/PRINCIPAL FINDINGS: Thioredoxin peroxidase
      1 (SjTPx-1) and four tandem repeat proteins (Sj1TR, Sj2TR, Sj4TR, Sj7TR) were
      initially evaluated against human sera. The previous test showed high sensitivity
      and specificity for antibody detection against SjTPx-1 and Sj7TR. In this study,
      the immunodiagnostic potential of these recombinant proteins was evaluated using
      enzyme-linked immunoassay on 50 water buffalo serum samples collected in Cagayan,
      the Philippines as compared with the soluble egg antigen (SEA). For specificity,
      3 goat serum samples positive with Fasciola hepatica were used and among the
      antigens used, only SEA showed cross-reaction. Stool PCR targeting the S.
      japonicum 82 bp mitochondrial NAD 1 gene was done to confirm the true positives
      and served as the standard test. Twenty three samples were positive for stool
      PCR. SjTPx-1 and Sj1TR gave the highest sensitivity among the recombinant
      proteins tested for water buffalo samples with 82.61% and 78.26% respectively
      which were higher than that of SEA (69.57%). CONCLUSIONS/SIGNIFICANCE: These
      results prove that SjTPx-1 works both for humans and water buffaloes making it a
      good candidate antigen for zoonotic diagnosis. Sj1TR showed good results for
      water buffaloes and therefore can also be used as a possible candidate for
      detecting animal schistosome infection.

PMID- 22953019
TI  - Severe hemorrhagic fever in strain 13/N guinea pigs infected with Lujo virus.
AB  - Lujo virus (LUJV) is a novel member of the Arenaviridae family that was first
      identified in 2008 after an outbreak of severe hemorrhagic fever (HF). In what
      was a small but rapidly progressing outbreak, this previously unknown virus was
      transmitted from the critically ill index patient to 4 attending healthcare
      workers. Four persons died during this outbreak, for a total case fatality of 80%
      (4/5). The suspected rodent source of the initial exposure to LUJV remains a
      mystery. Because of the ease of transmission, high case fatality, and novel
      nature of LUJV, we sought to establish an animal model of LUJV HF. Initial
      attempts in mice failed, but infection of inbred strain 13/N guinea pigs resulted
      in lethal disease. A total of 41 adult strain 13/N guinea pigs were infected with
      either wild-type LUJV or a full-length recombinant LUJV. Results demonstrated
      that strain 13/N guinea pigs provide an excellent model of severe and lethal LUJV
      HF that closely resembles what is known of the human disease. All infected
      animals experienced consistent weight loss (3-5% per day) and clinical illness
      characterized by ocular discharge, ruffled fur, hunched posture, and lethargy.
      Uniform lethality occurred by 11-16 days post-infection. All animals developed
      disseminated LUJV infection in various organs (liver, spleen, lung, and kidney),
      and leukopenia, lymphopenia, thrombocytopenia, coagulopathy, and elevated
      transaminase levels. Serial euthanasia studies revealed a temporal pattern of
      virus dissemination and increasing severity of disease, primarily targeting the
      liver, spleen, lungs, and lower gastrointestinal tract. Establishing an animal
      LUJV model is an important first step towards understanding the high
      pathogenicity of LUJV and developing vaccines and antiviral therapeutic drugs for
      this highly transmissible and lethal emerging pathogen.

PMID- 22953020
TI  - Exploratory space-time analyses of Rift Valley Fever in South Africa in 2008
      2011.
AB  - BACKGROUND: Rift Valley fever (RVF) is a zoonotic arbovirosis for which the
      primary hosts are domestic livestock (cattle, sheep and goats). RVF was first
      described in South Africa in 1950-1951. Mechanisms for short and long distance
      transmission have been hypothesised, but there is little supporting evidence.
      Here we describe RVF occurrence and spatial distribution in South Africa in 2008
      11, and investigate the presence of a contagious process in order to generate
      hypotheses on the different mechanisms of transmission. METHODOLOGY/PRINCIPAL
      FINDINGS: A total of 658 cases were extracted from World Animal Health
      Information Database. Descriptive statistics, epidemic curves and maps were
      produced. The space-time K-function was used to test for evidence of space-time
      interaction. Five RVF outbreak waves (one in 2008, two in 2009, one in 2010 and
      one in 2011) of varying duration, location and size were reported. About 70% of
      cases (n = 471) occurred in 2010, when the epidemic was almost country-wide. No
      strong evidence of space-time interaction was found for 2008 or the second wave
      in 2009. In the first wave of 2009, a significant space-time interaction was
      detected for up to one month and over 40 km. In 2010 and 2011 a significant
      intense, short and localised space-time interaction (up to 3 days and 15 km) was
      detected, followed by one of lower intensity (up to 2 weeks and 35 to 90 km).
      CONCLUSIONS/SIGNIFICANCE: The description of the spatiotemporal patterns of RVF
      in South Africa between 2008 and 2011 supports the hypothesis that during an
      epidemic, disease spread may be supported by factors other than active vector
      dispersal. Limitations of under-reporting and space-time K-function properties
      are discussed. Further spatial analyses and data are required to explain factors
      and mechanisms driving RVF spread.

PMID- 22953021
TI  - Changes in the safety paradigm with percutaneous coronary interventions in the
      modern era: Lessons learned from the ASCERT registry.
AB  - In the past, comparative effectiveness trials evaluating percutaneous coronary
      interventions (PCI), using either balloon angioplasty or bare metal stent (BMS)
      implantation, versus coronary artery bypass surgery (CABG) found similar survival
      rates at long-term follow-up with both revascularization strategies. Two major
      meta-analyses of these trials reported 5- and 6-year comparative effectiveness
      between PCI and CABG: one included only four trials that compared PCI with BMS
      implantation versus CABG whereas the largest one also included trials using
      balloon angioplasty. In these studies, the authors observed no survival
      differences between groups although a significant survival advantage was seen in
      diabetics treated with CABG and this benefit was also perceived in elderly
      patients. In both reports, number of involved vessels, presence of left anterior
      descending artery stenosis or poor left ventricular ejection fraction were no
      predictors of poor survival with PCI. Therefore, extent of the coronary artery
      disease (CAD) was not associated with poor outcome after PCI in the pre-drug
      eluting stent (DES) era. Recently, the ASCERT (Database Collaboration on the
      Comparative Effectiveness of Revascularization Strategies) registry found higher
      mortality rate with PCI in patients >= 65 years old in comparison with CABG, and
      advantages of surgery were seen in all subgroups including those at low risk. In
      this registry, PCI was accomplished by implantation of the first type of DES
      designs in 78% of cases. The intriguing observation of high mortality rate with
      PCI, including for non-diabetics and patients with two-vessel CAD, meaning a lack
      of clinical benefit with DES implantation, had not been seen previously. The
      study was not randomized, although its results are largely strengthened by its
      sample size. In this manuscript, the authors describe other registries and
      randomized trials reporting similar results supporting the findings of the
      aforementioned study and explore the reasons for these results, while also
      searching for potential solutions.

PMID- 22953022
TI  - Evaluation of the prevalence and severity of pain in patients with stable chronic
      heart failure.
AB  - AIM: To evaluate the prevalence and severity of pain in patients with chronic
      stable heart failure (HF) in an outpatient clinic setting. METHODS: This is a
      cross-sectional study evaluating symptoms of generalized or specific pain in
      patients with chronic stable heart failure. A standardized questionnaire
      (Edmonton Symptom Assessment System) was administered during a routine outpatient
      clinic visit. The severity of pain and other symptoms were assessed on a 10 point
      scale with 10 being the worst and 0 representing no symptoms. RESULTS: Sixty-two
      patients [age 56 +/- 13 years, 51 males, 11 females, mean ejection fraction (EF)
      33% +/- 17%] completed the assessment. Thirty-two patients (52%) reported any
      pain of various character and location such as chest, back, abdomen or the
      extremities, with a mean pain score of 2.5 +/- 3.1. Patients with an EF less than
      40% (n = 45, 73%) reported higher pain scores than patients with an EF greater
      than 40% (n = 17, 27%), scores were 3.1 +/- 3.3 vs 1.2 +/- 1.9, P < 0.001. Most
      frequent symptoms were tiredness (in 75% of patients), decreased wellbeing (84%),
      shortness of breath (SOB, 76%), and drowsiness (70%). The most severe symptom was
      tiredness with a score of 4.0 +/- 2.8, followed by decreased wellbeing (3.7 +/-
      2.7), SOB (3.6 +/- 2.8), and drowsiness (2.8 +/- 2.8). CONCLUSION: Pain appears
      to be prevalent and significantly affects quality of life in HF patients.
      Adequate pain assessment and management should be an integral part of chronic
      heart failure management.

PMID- 22953023
TI  - Effect of eicosapentaenoic acid on regional arterial stiffness: Assessment by
      tissue Doppler imaging.
AB  - AIM: To evaluate the effects of eicosapentaenoic acid (EPA) on regional arterial
      stiffness assessed by strain rate using tissue Doppler imaging. METHODS: Nineteen
      eligible patients were prospectively studied (mean age 62 +/- 8 years, 68% men).
      Subjects with large vessel complications and/or diabetes mellitus were excluded.
      The strain rate of the ascending aorta was measured by tissue Doppler imaging as
      an index of regional arterial stiffness, and brachial-ankle pulse wave velocity
      (baPWV) was measured as an index of degree of systemic arteriosclerosis. These
      indices were compared before and after administration of EPA at 1800 mg/d for one
      year. RESULTS: The plasma concentration of EPA increased significantly after EPA
      administration (3.0% +/- 1.1% to 8.5% +/- 2.9%, P < 0.001). There were no
      significant changes in baPWV (1765 +/- 335 cm/s to 1745 +/- 374 cm/s), low
      density lipoprotein cholesterol levels (114 +/- 29 mg/dL to 108 +/- 28 mg/dL), or
      systolic blood pressure (131 +/- 16 mmHg to 130 +/- 13 mmHg) before and after EPA
      administration. In contrast, the strain rate was significantly increased by
      administration of EPA (19.2 +/- 5.6 s(-1), 23.0 +/- 6.6 s(-1), P < 0.05).
      CONCLUSION: One year of administration of EPA resulted in an improvement in
      regional arterial stiffness which was independent of blood pressure or serum
      cholesterol levels.

PMID- 22953024
TI  - MRI-guided ablation of wide complex tachycardia in a univentricular heart.
AB  - Magnetic resonance imaging can be used for preprocedural assessment of complex
      anatomy for radiofrequency (RF) ablations, e.g., in a univentricular heart. This
      case report features the treatment of a young patient with a functionally
      univentricular heart who suffered from persistent sudden onset tachycardia with
      wide complexes that required RF ablation as treatment.

PMID- 22953025
TI  - Acute coronary syndrome in a patient with a single coronary artery arising from
      the right sinus of Valsalva.
AB  - Coronary artery anomalies are usually encountered as coincidental findings during
      coronary angiography or at autopsy. Life threatening symptoms, such as
      arrhythmias, syncope, myocardial infarction, or sudden death, can occur in up to
      20% of patients. However, the majority of anomalies (80%) are benign and
      asymptomatic. A single coronary artery (SCA) is one of the most rarely seen
      coronary anomalies with an incidence of 0.05%. We report the case of a 55-year
      old male patient who presented with symptoms of chest pain associated with an
      acute myocardial infarction. Coronary angiography revealed an anomalous left main
      coronary artery (LMCA) originating from the right coronary ostium, and an
      occluded distal right coronary artery. The occluded distal right coronary artery
      was successfully treated by thrombosuction and stenting. In order to confirm the
      origin and course of the SCA, multi-slice computed tomography (MSCT) of the heart
      was performed after coronary angiography. MSCT showed that the anomalous LMCA
      originated from the right coronary artery ostium and then passed the
      interventricular septum, instead of being intra arterial, and under the right
      ventricular infundibulum. The anomalous LMCA was classified as R-II S subtype
      according to Lipton's classification.

PMID- 22953026
TI  - Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet.
AB  - Colorectal cancer (CRC) is a leading cause of cancer deaths in the United States.
      Various risk factors have been associated with CRC including increasing age and
      diet. Epidemiological and experimental studies have implicated a diet high in fat
      as an important risk factor for colon cancer. High fat diets can promote obesity
      resulting in insulin resistance and inflammation and the development of oxidative
      stress, increased cell proliferation, and suppression of apoptosis. Because of
      the high consumption of dietary fats, especially saturated fats, by Western
      countries, it is of interest to see if non-nutrient food factors might be
      effective in preventing or delaying CRC in the presence of high saturated fat
      intake. Curcumin (Curcuma longa), the main yellow pigment in turmeric, was
      selected to test because of its reported anti-tumor activity. APC Min mice, which
      develop intestinal polyps and have many molecular features of CRC, were fed a
      diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral
      mixture (HFD) with or without 0.5% curcumin. These cohorts were compared to APC
      Min mice receiving standard rodent chow (RC) with 8% fat. APC Min mice fed the
      HFD for 3 months had a 23% increase in total number of polyps compared to APC Min
      mice on RC. Curcumin was able to significantly reverse the accelerated polyp
      development associated with the HFD suggesting it may be effective clinically in
      helping prevent colon cancer even when ingesting high amounts of fatty foods. The
      anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis
      and increased efficiency of DNA repair. Since curcumin prevented the gain in body
      weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism
      may also be a factor.

PMID- 22953027
TI  - Pathobiology of aging: an old problem gets a new look.

PMID- 22953028
TI  - Resveratrol has protective effects against airway remodeling and airway
      hyperreactivity in a murine model of allergic airways disease.
AB  - BACKGROUND: New therapies for asthma which can address three main interrelated
      features of the disease, airway inflammation, airway remodeling and airway
      hyperreactivity, are urgently required. Resveratrol, a well known red wine
      polyphenol has received much attention due to its potential anti-aging
      properties. This compound is an agonist of silent information regulator two
      histone deacetylases and has many effects that are relevant to key aspects of the
      pathophysiology of asthma including inflammation, cell proliferation and
      fibrosis. Therefore, resveratrol may offer a novel asthma therapy that
      simultaneously inhibits airway inflammation, and airway remodeling which are the
      main contributors to airway hyperreactivity and irreversible lung function loss.
      METHODS: We evaluated the effects of systemic resveratrol treatment in a murine
      model of chronic allergic airways disease which displays most of the
      clinicopathological features of severe human asthma. Wild-type Balb/c mice with
      allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle
      control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell
      counts and histological examination of lung tissue sections. Further, remodeling
      was assessed by morphometric analysis and lung function was assessed by invasive
      plethysmography measurement of airway resistance and dynamic compliance. RESULTS:
      Mice treated with resveratrol exhibited reduced tissue inflammation as compared
      to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in
      reduced subepithelial collagen deposition as compared to vehicle treated mice
      (p<0.05) and attenuated airway hyperreactivity (p<0.05). CONCLUSIONS: These novel
      findings demonstrate that treatment with resveratrol can reduce structural airway
      remodeling changes and hyperreactivity. This has important implications for the
      development of new therapeutic approaches to asthma.

PMID- 22953029
TI  - Broad segmental progeroid changes in short-lived Ercc1(-/Delta7) mice.
AB  - Genome maintenance is considered a prime longevity assurance mechanism as
      apparent from many progeroid human syndromes that are caused by genome
      maintenance defects. The ERCC1 protein is involved in three genome maintenance
      systems: nucleotide excision repair, interstrand cross-link repair, and
      homologous recombination. Here we describe in-life and post-mortem observations
      for a hypomorphic Ercc1 variant, Ercc1(-/Delta7), which is hemizygous for a
      single truncated Ercc1 allele, encoding a protein lacking the last seven amino
      acids. Ercc1(-/Delta7) mice were much smaller and median life span was markedly
      reduced compared to wild-type siblings: 20 and 118 weeks, respectively. Multiple
      signs and symptoms of aging were found to occur at an accelerated rate in the
      Ercc1(-/Delta7) mice as compared to wild-type controls, including a decline in
      weight of both whole body and various organs, numerous histopathological lesions,
      and immune parameters. Together they define a segmental progeroid phenotype of
      the Ercc1(-/Delta7) mouse model.

PMID- 22953030
TI  - The anti-tumor effects of calorie restriction are correlated with reduced
      oxidative stress in ENU-induced gliomas.
AB  - The anti-tumor effects of calorie restriction (CR) and the possible underlying
      mechanisms were investigated using ethylnitrosourea (ENU)-induced glioma in rats.
      ENU was given transplacentally at gestational day 15, and male offspring were
      used in this experiment. The brain from 4-, 6-, and 8-month-old rats fed either
      ad libitum (AL) or calorie-restricted diets (40% restriction of total calories
      compared to AL rats) was studied. Tumor burden was assessed by comparing the
      number and size of gliomas present in sections of the brain. Immunohistochemical
      analysis was used to document lipid peroxidation [4-hydroxy-2-nonenal (HNE) and
      malondialdehyde (MDA)], protein oxidation (nitrotyrosine), glycation and AGE
      formation [methylglyoxal (MG) and carboxymethyllysine (CML)], cell proliferation
      activity [proliferating cell nuclear antigen (PCNA)], cell death [single-stranded
      DNA (ssDNA)], presence of thioredoxin 1 (Trx1), and presence of heme oxygenase-1
      (HO-1) associated with the development of gliomas. The results showed that the
      number of gliomas did not change with age in the AL groups; however, the average
      size of the gliomas was significantly larger in the 8-month-old group compared to
      that of the younger groups. Immunopositivity was observed mainly in tumor cells
      and reactive astrocytes in all histological types of ENU-induced glioma.
      Immunopositive areas for HNE, MDA, nitrotyrosine, MG, CML, HO-1, and Trx1
      increased with the growth of gliomas. The CR group showed both reduced number and
      size of gliomas, and tumors exhibited less accumulation of oxidative damage,
      decreased formation of glycated end products, and a decreased presence of HO-1
      and Trx1 compared to the AL group. Furthermore, gliomas of the CR group showed
      less PCNA positive and more ssDNA positive cells, which are correlated to the
      retarded growth of tumors. Interestingly, we also discovered that the anti-tumor
      effects of CR were associated with decreased hypoxia-inducible factor-1alpha (HIF
      1alpha) levels in normal brain tissue. Our results are very exciting because they
      not only demonstrate the anti-tumor effects of CR in gliomas, but also indicate
      the possible underlying mechanisms, i.e. anti-tumor effects of CR observed in
      this investigation are associated with reduced accumulation of oxidative damage,
      decreased formation of glycated end products, decreased presence of HO-1 and
      Trx1, reduced cell proliferation and increased apoptosis, and decreased levels of
      HIF-1alpha.

PMID- 22953031
TI  - The mouse as a model for understanding chronic diseases of aging: the
      histopathologic basis of aging in inbred mice.
AB  - Inbred mice provide a unique tool to study aging populations because of the
      genetic homogeneity within an inbred strain, their short life span, and the tools
      for analysis which are available. A large-scale longitudinal and cross-sectional
      aging study was conducted on 30 inbred strains to determine, using
      histopathology, the type and diversity of diseases mice develop as they age.
      These data provide tools that when linked with modern in silico genetic mapping
      tools, can begin to unravel the complex genetics of many of the common chronic
      diseases associated with aging in humans and other mammals. In addition, novel
      disease models were discovered in some strains, such as rhabdomyosarcoma in old
      A/J mice, to diseases affecting many but not all strains including pseudoxanthoma
      elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive
      data set is now available online and provides a useful tool to help better
      understand strain-specific background diseases that can complicate interpretation
      of genetically engineered mice and other manipulatable mouse studies that utilize
      these strains.

PMID- 22953032
TI  - Practical pathology of aging mice.
AB  - Old mice will have a subset of lesions as part of the progressive decline in
      organ function that defines aging. External and palpable lesions will be noted by
      the research, husbandry, or veterinary staff during testing, cage changing, or
      physical exams. While these readily observable lesions may cause alarm, not all
      cause undue distress or are life-threatening. In aging research, mice are
      maintained until near end of life that, depending on strain and genetic
      manipulation, can be upwards of 33 months. Aging research has unique welfare
      issues related to age-related decline, debilitation, fragility, and associated
      pain of chronic diseases. An effective aging research program includes the
      collaboration and education of the research, husbandry, and veterinary staff, and
      of the members of the institution animal care and use committee. This
      collaborative effort is critical to humanely maintaining older mice and
      preventing excessive censorship due to non-lethal diseases. Part of the
      educational process is becoming familiar with how old mice appear clinically, at
      necropsy and histopathologically. This baseline knowledge is important in making
      the determination of humane end points, defining health span, contributing causes
      of death and effects of interventions. The goal of this paper is to introduce
      investigators to age-associated diseases and lesion patterns in mice from
      clinical presentation to pathologic assessment. To do so, we present and
      illustrate the common clinical appearances, necropsy and histopathological
      lesions seen in subsets of the aging colonies maintained at the University of
      Washington.

PMID- 22953033
TI  - Growth hormone, inflammation and aging.
AB  - Mutant animals characterized by extended longevity provide valuable tools to
      study the mechanisms of aging. Growth hormone and insulin-like growth factor-1
      (IGF-1) constitute one of the well-established pathways involved in the
      regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH
      deficiency as well as growth hormone receptor/growth hormone binding protein
      knockout (GHRKO) mice characterized by GH resistance live significantly longer
      than genetically normal animals. During normal aging of rodents and humans there
      is increased insulin resistance, disruption of metabolic activities and decline
      of the function of the immune system. All of these age related processes promote
      inflammatory activity, causing long term tissue damage and systemic chronic
      inflammation. However, studies of long living mutants and calorie restricted
      animals show decreased pro-inflammatory activity with increased levels of anti
      inflammatory adipokines such as adiponectin. At the same time, these animals have
      improved insulin signaling and carbohydrate homeostasis that relate to
      alterations in the secretory profile of adipose tissue including increased
      production and release of anti-inflammatory adipokines. This suggests that
      reduced inflammation promoting healthy metabolism may represent one of the major
      mechanisms of extended longevity in long-lived mutant mice and likely also in the
      human.

PMID- 22953034
TI  - Breast tumors in PyMT transgenic mice expressing mitochondrial catalase have
      decreased labeling for macrophages and endothelial cells.
AB  - We show by immunohistochemical labeling that prominent cell types in the tumor
      microenvironment of PyMT transgenic mice are tumor-associated macrophages (TAMs)
      and endothelial cells, and that both populations are decreased in the presence of
      mitochondrial targeted catalase (mCAT). This observation suggests that
      mitochondrial ROS can drive tumor invasiveness in conjunction with the presence
      of TAMs and increased angiogenesis. Since primary PyMT tumor cells expressing
      mCAT undergo increased apoptosis, mitochondrial antioxidants might be attractive
      anti-tumor agents.

PMID- 22953036
TI  - Rapamycin selectively alters serum chemistry in diabetic mice.
AB  - The study was undertaken to explore the effect of rapamycin, an anti-inflammatory
      agent, on the metabolic profile of type 2 diabetic mice. Seven-month-old diabetic
      db/db mice and their lean littermate non-diabetic controls (db/m) were randomized
      to receive control chow or chow mixed with rapamycin (2.24 mg/kg/day) (each group
      n =20, males and females) for 4 months and sacrificed. Serum samples were
      analyzed for the measurement of glucose, creatinine, blood urea nitrogen (BUN),
      alkaline phosphatase (ALP), alanine aminotransferase (ALT), total cholesterol,
      total triglyceride, and total protein, using the automated dry chemistry
      analysis. Rapamycin elevated serum glucose in female diabetic mice. Serum
      creatinine tended to be higher in diabetic mice but was not affected by
      rapamycin; there was no difference in BUN levels among the groups. Serum ALP was
      elevated in diabetic mice and rapamycin lowered it only in female diabetic mice;
      serum ALT levels were increased in female diabetic mice, unaffected by rapamycin.
      Serum total protein was elevated in diabetic mice of both genders but was not
      affected by rapamycin. Diabetic mice from both genders had elevated serum
      cholesterol and triglycerides; rapamycin did not affect serum cholesterol but
      decreased serum total triglycerides in male diabetic mice. We conclude that
      rapamycin elicits complex metabolic responses in aging diabetic mice, worsening
      hyperglycemia in females but improving ALP in female diabetic and total
      triglycerides in male diabetic mice, respectively. The metabolic effects of
      rapamycin should be considered while performing studies with rapamycin in mice.

PMID- 22953035
TI  - Potential of chromatin modifying compounds for the treatment of Alzheimer's
      disease.
AB  - Alzheimer's disease is a very common progressive neurodegenerative disorder
      affecting the learning and memory centers in the brain. The hallmarks of disease
      are the accumulation of beta-amyloid neuritic plaques and neurofibrillary tangles
      formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently
      incurable and there is an intense interest in the development of new potential
      therapies. Chromatin modifying compounds such as sirtuin modulators and histone
      deacetylase inhibitors have been evaluated in models of Alzheimer's disease with
      some promising results. For example, the natural antioxidant and sirtuin 1
      activator resveratrol has been shown to have beneficial effects in animal models
      of disease. Similarly, numerous histone deacetylase inhibitors including
      Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate
      reduction have shown promising results in models of Alzheimer's disease. These
      beneficial effects include a reduction of beta-amyloid production and
      stabilization of tau protein. In this review we provide an overview of the
      histone deacetylase enzymes, with a focus on enzymes that have been identified to
      have an important role in the pathobiology of Alzheimer's disease. Further, we
      discuss the potential for pharmacological intervention with chromatin modifying
      compounds that modulate histone deacetylase enzymes.

PMID- 22953037
TI  - Reduction of glucose intolerance with high fat feeding is associated with anti
      inflammatory effects of thioredoxin 1 overexpression in mice.
AB  - Aging is associated with reduced ability to maintain normal glucose homeostasis.
      It has been suggested that an age-associated increase in chronic pro-inflammatory
      state could drive this reduction in glucoregulatory function. Thioredoxins (Trx)
      are oxido-reductase enzymes that play an important role in the regulation of
      oxidative stress and inflammation. In this study, we tested whether
      overexpression of Trx1 in mice [Tg(TRX1)(+/0)] could protect from glucose
      metabolism dysfunction caused by high fat diet feeding. Body weight and fat mass
      gains with high fat feeding were similar in Tg(TRX1)(+/0) and wild-type mice;
      however, high fat diet induced glucose intolerance was reduced in Tg(TRX1)(+/0)
      mice relative to wild-type mice. In addition, expression of the pro-inflammatory
      cytokine TNF-alpha was reduced in adipose tissue of Tg(TRX1)(+/0) mice compared
      to wild-type mice. These findings suggest that activation of thioredoxins may be
      a potential therapeutic target for maintenance of glucose metabolism with obesity
      or aging.

PMID- 22953038
TI  - Investigation of the biological properties of Cinnulin PF in the context of
      diabetes: mechanistic insights by genome-wide mRNA-Seq analysis.
AB  - The accumulating evidence of the beneficial effects of cinnamon (Cinnamomum
      burmanni) in type-2 diabetes, a chronic age-associated disease, has prompted the
      commercialisation of various supplemental forms of the spice. One such
      supplement, Cinnulin PF((r)), represents the water soluble fraction containing
      relatively high levels of the double-linked procyanidin type-A polymers of
      flavanoids. The overall aim of this study was to utilize genome-wide mRNA-Seq
      analysis to characterise the changes in gene expression caused by Cinnulin PF in
      immortalised human keratinocytes and microvascular endothelial cells, which are
      relevant with respect to diabetic complications. In summary, our findings provide
      insights into the mechanisms of action of Cinnulin PF in diabetes and diabetic
      complications. More generally, we identify relevant candidate genes which could
      provide the basis for further investigation.

PMID- 22953040
TI  - B16 melanoma tumor growth is delayed in mice in an age-dependent manner.
AB  - A major risk factor for cancer is increasing age, which suggests that syngeneic
      tumor implants in old mice would grow more rapidly. However, various reports have
      suggested that old mice are not as permissive to implanted tumor cells as young
      mice. In order to determine and characterize the age-related response to B16
      melanoma, we implanted 5*10(5) tumor cells into 8, 16, 24, and 32-month-old male
      C57BL/6 (B6) and C57BL/6*BALB/c F1 (CB6 F1) mice subcutaneously in the inguinal
      and axillary spaces, or intradermally in the lateral flank. Results showed
      decreased tumor volume with increasing age, which varied according to mouse
      genetic background and the implanted site. The B6 strain showed robust tumor
      growth at 8 months of age at the inguinal implantation site, with an average
      tumor volume of 1341.25 mm(3). The 16, 24, and 32-month age groups showed a
      decrease in tumor growth with tumor volumes of 563.69, 481.02, and 264.55 mm(3),
      respectively (p<=0.001). The axillary implantation site was less permissive in 8
      month-old B6 mice with an average tumor volume of 761.52 mm(3). The 24- and 32
      month age groups showed a similar decrease in tumor growth with tumor volumes of
      440 and 178.19 mm(3), respectively (p<=0.01). The CB6F1 strain was not as tumor
      permissive at 8 months of age as B6 mice with average tumor volumes of 446.96 and
      426.91 mm(3) for the inguinal and axillary sites, respectively. There was a
      decrease in tumor growth at 24 months of age at both inguinal and axillary sites
      with an average tumor volume of 271.02 and 249.12 mm(3), respectively (p<=0.05).
      The strain dependence was not apparent in 8-month-old mice injected intradermally
      with B16 melanoma cells, with average tumor volumes of 736.82 and 842.85 mm(3)
      for B6 and CB6 F1, respectively. However, a strain difference was seen in 32
      month-old B6 mice with an average decrease in tumor volume of 250.83 mm(3)
      (p<=0.01). In contrast, tumor growth significantly decreased earlier in CB6 F1
      mice with average tumor volumes of 417.62 and 216.34 mm(3) in the 16- and 24
      month age groups, respectively (p<=0.005). Histologically, implanted tumors in
      young mice exhibited characteristics of aggressive, rapidly growing tumor cells
      including high vascularity, mitosis, and invasiveness compared to tumors in old
      mice. We contend that the decrease in B16 melanoma tumor growth seen with
      increasing age in B6 and CB6 F1 mice represents a biological process, which we
      are calling age-dependent cancer resistance (ADCR). Our data provide a detailed
      description of conditions necessary to use the model to investigate the
      mechanisms of ADCR and determine its biological and clinical relevance.

PMID- 22953039
TI  - Age-dependent changes in innate immune phenotype and function in rhesus macaques
      (Macaca mulatta).
AB  - Aged individuals are more susceptible to infections due to a general decline in
      immune function broadly referred to as immune senescence. While age-related
      changes in the adaptive immune system are well documented, aging of the innate
      immune system remains less well understood, particularly in nonhuman primates. A
      more robust understanding of age-related changes in innate immune function would
      provide mechanistic insight into the increased susceptibility of the elderly to
      infection. Rhesus macaques have proved a critical translational model for aging
      research, and present a unique opportunity to dissect age-dependent modulation of
      the innate immune system. We examined age-related changes in: (i) innate immune
      cell frequencies; (ii) expression of pattern recognition receptors (PRRs) and
      innate signaling molecules; (iii) cytokine responses of monocytes and dendritic
      cells (DC) following stimulation with PRR agonists; and (iv) plasma cytokine
      levels in this model. We found marked changes in both the phenotype and function
      of innate immune cells. This included an age-associated increased frequency of
      myeloid DC (mDC). Moreover, we found toll-like receptor (TLR) agonists
      lipopolysaccharide (TLR4), fibroblast stimulating ligand-1 (TLR2/6), and ODN2006
      (TLR7/9) induced reduced cytokine responses in aged mDC. Interestingly, with the
      exception of the monocyte-derived TNFalpha response to LPS, which increased with
      age, TNFalpha, IL-6, and IFNalpha responses declined with age. We also found that
      TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing
      protein (SARM), were all expressed at lower levels in young animals. By contrast,
      absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in
      aged animals. Together, these observations indicate that several parameters of
      innate immunity are significantly modulated by age and contribute to differential
      immune function in aged macaques.

PMID- 22953041
TI  - Pd/C synthesized with citric acid: an efficient catalyst for hydrogen generation
      from formic acid/sodium formate.
AB  - A highly efficient hydrogen generation from formic acid/sodium formate aqueous
      solution catalyzed by in situ synthesized Pd/C with citric acid has been
      successfully achieved at room temperature. Interestingly, the presence of citric
      acid during the formation and growth of the Pd nanoparticles on carbon can
      drastically enhance the catalytic property of the resulted Pd/C, on which the
      conversion and turnover frequency for decomposition of formic acid/sodium formate
      system can reach the highest values ever reported of 85% within 160 min and 64
      mol H(2) mol(-1) catalyst h(-1), respectively, at room temperature. The present
      simple, low cost, but highly efficient CO-free hydrogen generation system at room
      temperature is believed to greatly promote the practical application of formic
      acid system on fuel cells.

PMID- 22953042
TI  - Coupling carbon nanotube mechanics to a superconducting circuit.
AB  - The quantum behaviour of mechanical resonators is a new and emerging field driven
      by recent experiments reaching the quantum ground state. The high frequency,
      small mass, and large quality-factor of carbon nanotube resonators make them
      attractive for quantum nanomechanical applications. A common element in
      experiments achieving the resonator ground state is a second quantum system, such
      as coherent photons or a superconducting device, coupled to the resonators
      motion. For nanotubes, however, this is a challenge due to their small size.
      Here, we couple a carbon nanoelectromechanical (NEMS) device to a superconducting
      circuit. Suspended carbon nanotubes act as both superconducting junctions and
      moving elements in a Superconducting Quantum Interference Device (SQUID). We
      observe a strong modulation of the flux through the SQUID from displacements of
      the nanotube. Incorporating this SQUID into superconducting resonators and qubits
      should enable the detection and manipulation of nanotube mechanical quantum
      states at the single-phonon level.

PMID- 22953043
TI  - Flexible and tunable silicon photonic circuits on plastic substrates.
AB  - Flexible microelectronics has shown tremendous promise in a broad spectrum of
      applications, especially those that cannot be addressed by conventional
      microelectronics in rigid materials and constructions. These unconventional yet
      important applications range from flexible consumer electronics to conformal
      sensor arrays and biomedical devices. A recent paradigm shift in implementing
      flexible electronics is to physically transfer highly integrated devices made in
      high-quality, crystalline semiconductors on to plastic substrates. Here we
      demonstrate a flexible form of silicon photonics using the transfer-and-bond
      fabrication method. Photonic circuits including interferometers and resonators
      have been transferred onto flexible plastic substrates with preserved
      functionalities and performance. By mechanically deforming, the optical
      characteristics of the devices can be tuned reversibly over a remarkably large
      range. The demonstration of the new flexible photonic systems based on the
      silicon-on-plastic (SOP) platform could open the door to many future
      applications, including tunable photonics, optomechanical sensors and
      biomechanical and bio-photonic probes.

PMID- 22953044
TI  - Role of dislocation movement in the electrical conductance of nanocontacts.
AB  - Dislocation is a lattice imperfection of crystalline materials. Dislocation
      movement is induced during plastic deformation and influences the mechanical
      properties. Although the role of dislocation in mechanical properties has been
      well understood, the role of dislocation in electrical properties is completely
      lacking. Only Matthiessen's rule addresses the electrical influence of
      dislocations at the macroscale. Here, we show that the electrical conductance
      change due to dislocations and show their movements through in situ observation
      of a gold nanocontact. The density of the dislocations in the gold nanocontact
      did not affect the electrical conductance. The repeated and discrete dislocation
      movements resulted in an electrical conductance oscillation. Our results
      demonstrate how dislocations and their movements affect electric conductance at
      the nanoscale. This instability issue will cause a big problem for future
      electric devices such as ultra low power electric devices and nanowire
      photovoltaic devices.

PMID- 22953045
TI  - Room-temperature magnetic ordering in functionalized graphene.
AB  - Despite theoretical predictions, the question of room-temperature magnetic order
      in graphene must be conclusively resolved before graphene can fully achieve its
      potential as a spintronic medium. Through scanning tunneling microscopy (STM) and
      point I-V measurements, the current study reveals that unlike pristine samples,
      graphene nanostructures, when functionalized with aryl radicals, can sustain
      magnetic order. STM images show 1-D and 2-D periodic super-lattices originating
      from the functionalization of a single sub-lattice of the bipartite graphene
      structure. Field-dependent super-lattices in 3-nm wide "zigzag" nanoribbons
      indicate local moments with parallel and anti-parallel ordering along and across
      the edges, respectively. Anti-parallel ordering is observed in 2-D segments with
      sizes of over 20 nm. The field dependence of STM images and point I-V curves
      indicates a spin polarized local density of states (LDOS), an out-of-plane
      anisotropy field of less than 10 Oe, and an exchange coupling field of 100 Oe at
      room temperature.

PMID- 22953046
TI  - Superconductivity in bundles of double-wall carbon nanotubes.
AB  - We present electrical and thermal specific heat measurements that show
      superconductivity in double-wall carbon nanotube (DWCNT) bundles. Clear evidence,
      comprising a resistance drop as a function of temperature, magnetoresistance and
      differential resistance signature of the supercurrent, suggest an intrinsic
      superconducting transition below 6.8 K for one particular sample. Additional
      electrical data not only confirm the existence of superconductivity, but also
      indicate the T(c) distribution that can arise from the diversity in the diameter
      and chirality of the DWCNTs. A broad superconducting anomaly is observed in the
      specific heat of a bulk DWCNT sample, which yields a T(c) distribution that
      correlates well with the range of the distribution obtained from the electrical
      data. As quasi one dimensionality of the DWCNTs dictates the existence of
      electronic density of state peaks, confirmation of superconductivity in this
      material system opens the exciting possibility of tuning the T(c) through the
      application of a gate voltage.

PMID- 22953047
TI  - Experimental quantum error detection.
AB  - Faithful transmission of quantum information is a crucial ingredient in quantum
      communication networks. To overcome the unavoidable decoherence in a noisy
      channel, to date, many efforts have been made to transmit one state by consuming
      large numbers of time-synchronized ancilla states. However, such huge demands of
      quantum resources are hard to meet with current technology and this restricts
      practical applications. Here we experimentally demonstrate quantum error
      detection, an economical approach to reliably protecting a qubit against bit-flip
      errors. Arbitrary unknown polarization states of single photons and entangled
      photons are converted into time bins deterministically via a modified Franson
      interferometer. Noise arising in both 10 m and 0.8 km fiber, which induces
      associated errors on the reference frame of time bins, is filtered when photons
      are detected. The demonstrated resource efficiency and state independence make
      this protocol a promising candidate for implementing a real-world quantum
      communication network.

PMID- 22953048
TI  - Strongly linearly polarized low threshold lasing of all organic photonic
      quasicrystals.
AB  - Lasing is obtained from a two-dimensional (2D) Penrose photonic quasicrystal made
      of a low index contrast material of holographic polymer dispersed liquid crystals
      (H-PDLCs) that enables a substantial reduction in the optical pumping threshold.
      This lasing architecture further allows for excellent linear polarization
      characteristics as well as wide directional dependence. The pumping threshold is
      fivefold lower than that obtained from the 2D defect-free photonic crystals
      fabricated under similar conditions. These properties make H-PDLC photonic
      quasicrystal promising for a new type of all organic miniature lasers.

PMID- 22953049
TI  - Towards coherent spin precession in pure-spin current.
AB  - Non-local spin injection in lateral spin valves generates a pure spin current
      which is a diffusive flow of spins (i.e. spin angular momentums) with no net
      charge flow. The diffusive spins lose phase coherency in precession while
      undergoing frequent collisions and these events lead to a broad distribution of
      the dwell time in a transport channel between the injector and the detector. Here
      we show the lateral spin-valves with dual injectors enable us to detect a genuine
      in-plane precession signal from the Hanle effect, demonstrating the phase
      coherency in the in-plane precession is improved with an increase of the channel
      length. The coherency in the spin precession shows a universal behavior as a
      function of the normalized separation between the injector and the detector in
      material-independent fashion for metals and semiconductors including graphene.

PMID- 22953051
TI  - Optimizing functional network representation of multivariate time series.
AB  - By combining complex network theory and data mining techniques, we provide
      objective criteria for optimization of the functional network representation of
      generic multivariate time series. In particular, we propose a method for the
      principled selection of the threshold value for functional network reconstruction
      from raw data, and for proper identification of the network's indicators that
      unveil the most discriminative information on the system for classification
      purposes. We illustrate our method by analysing networks of functional brain
      activity of healthy subjects, and patients suffering from Mild Cognitive
      Impairment, an intermediate stage between the expected cognitive decline of
      normal aging and the more pronounced decline of dementia. We discuss extensions
      of the scope of the proposed methodology to network engineering purposes, and to
      other data mining tasks.

PMID- 22953050
TI  - Minimal conformational plasticity enables TCR cross-reactivity to different MHC
      class II heterodimers.
AB  - Successful immunity requires that a limited pool of alphabeta T-cell receptors
      (TCRs) provide cover for a vast number of potential foreign peptide antigens
      presented by 'self' major histocompatibility complex (pMHC) molecules. Structures
      of unligated and ligated MHC class-I-restricted TCRs with different ligands,
      supplemented with biophysical analyses, have revealed a number of important
      mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the
      influenza hemagglutinin antigen (HA(306-318)) presented by HLA-DR1 or HLA-DR4
      represents an ideal system for interrogating pMHC-II antigen recognition.
      Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it
      to both complex structures. Despite a relatively rigid binding mode, HA1.7 T
      cells could tolerate mutations in key contact residues within the peptide
      epitope. Thermodynamic analysis revealed that limited plasticity and extreme
      favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross
      react with HA(306-318) presented by multiple MHC-II alleles.

PMID- 22953052
TI  - Chemical structure of Retro-2, a compound that protects cells against ribosome
      inactivating proteins.
AB  - Shiga-like toxins and ricin are ribosome-inactivating proteins (RIPs) that are
      lethal to mammals and pose a global health threat. No clinical vaccines or
      therapeutics currently exist to protect against these RIPs. Two small molecules
      (Retro-1 and Retro-2) were discovered with high-throughput screening and reported
      for their protection of cells against RIPs. Of great significance, Retro-2,
      reported as (E)-2-(((5-methylthiophen-2-yl)methylene)amino)-N-phenylbenzamide,
      fully protected mice from lethal nasal challenge with ricin. Herein, we report
      studies showing that the chemical structure of Retro-2 is (+/-)-2-(5
      methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one rather than (E)-2
      (((5-methylthiophen-2-yl)methylene)amino)-N-phenylbenzamide. The latter is an
      achiral molecule that converts spontaneously to the former, which is a racemate
      and showed cell protection against RIPs. This calls for attention to (+/-)-2-(5
      methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one as a promising RIP
      inhibitor and for chemical characterization of drug leads obtained from high
      throughput screens.

PMID- 22953053
TI  - On the existence of a threshold for preventive behavioral responses to suppress
      epidemic spreading.
AB  - The spontaneous behavioral responses of individuals to the progress of an
      epidemic are recognized to have a significant impact on how the infection
      spreads. One observation is that, even if the infection strength is larger than
      the classical epidemic threshold, the initially growing infection can diminish as
      the result of preventive behavioral patterns adopted by the individuals. In order
      to investigate such dynamics of the epidemic spreading, we use a simple
      behavioral model coupled with the individual-based SIS epidemic model where
      susceptible individuals adopt a preventive behavior when sensing infection. We
      show that, given any infection strength and contact topology, there exists a
      region in the behavior-related parameter space such that infection cannot survive
      in long run and is completely contained. Several simulation results, including a
      spreading scenario in a realistic contact network from a rural district in the
      State of Kansas, are presented to support our analytical arguments.

PMID- 22953054
TI  - How random are online social interactions?
AB  - The massive amounts of data that social media generates has facilitated the study
      of online human behavior on a scale unimaginable a few years ago. At the same
      time, the much discussed apparent randomness with which people interact online
      makes it appear as if these studies cannot reveal predictive social behaviors
      that could be used for developing better platforms and services. We use two large
      social databases to measure the mutual information entropy that both individual
      and group actions generate as they evolve over time. We show that user's
      interaction sequences have strong deterministic components, in contrast with
      existing assumptions and models. In addition, we show that individual
      interactions are more predictable when users act on their own rather than when
      attending group activities.

PMID- 22953055
TI  - Hydrolysis of virgin coconut oil using immobilized lipase in a batch reactor.
AB  - Hydrolysis of virgin coconut oil (VCO) had been carried out by using an
      immobilised lipase from Mucor miehei (Lipozyme) in a water-jacketed batch
      reactor. The kinetic of the hydrolysis was investigated by varying the parameters
      such as VCO concentration, enzyme loading, water content, and reaction
      temperature. It was found that VCO exhibited substrate inhibition at the
      concentration more than 40% (v/v). Lipozyme also achieved the highest production
      of free fatty acids, 4.56 mM at 1% (w/v) of enzyme loading. The optimum water
      content for VCO hydrolysis was 7% (v/v). A relatively high content of water was
      required because water was one of the reactants in the hydrolysis. The progress
      curve and the temperature profile of the enzymatic hydrolysis also showed that
      Lipozyme could be used for free fatty acid production at the temperature up to 50
      degrees C. However, the highest initial reaction rate and the highest yield of
      free fatty acid production were at 45 and 40 degrees C, respectively. A 100 hours
      of initial reaction time has to be compensated in order to obtain the highest
      yield of free fatty acid production at 40 degrees C.

PMID- 22953056
TI  - Predicting depression with psychopathology and temperament traits: the northern
      Finland 1966 birth cohort.
AB  - We studied the concurrent, predictive, and discriminate validity of
      psychopathology scales (e.g., schizotypal and depressive) and temperament traits
      for hospitalisations due to major depression. Temperament, perceptual aberration,
      physical and social anhedonia, Depression Subscale of Symptom Checklist (SCL-D),
      Hypomanic Personality Scale, Schizoidia Scale, and Bipolar II Scale were
      completed as part of the 31-year follow-up survey of the prospective Northern
      Finland 1966 Birth Cohort (n = 4941; 2214 males). Several of the scales were
      related to depression. Concurrent depression was especially related to higher
      perceptual aberration (effect size when compared to controls, d = 1.29),
      subsequent depression to high scores in SCL-D (d = 0.48). Physical anhedonia was
      lower in subjects with subsequent depression than those with other psychiatric
      disorders (d = -0.33, nonsignificant). Participants with concurrent (d = 0.70)
      and subsequent (d = 0.54) depression had high harm avoidance compared to
      controls, while differences compared to other psychiatric patients were small.
      Subjects with depression differed from healthy controls in most of the scales.
      Many of the scales were useful predictors for future hospital treatments, but
      were not diagnosis-specific. High harm avoidance is a potential indicator for
      subsequent depression.

PMID- 22953058
TI  - Temporal lobe epilepsy after refractory status epilepticus: an illustrative case
      and review of the literature.
AB  - New onset refractory status epilepticus (NORSE) is a relatively newly defined
      disease entity, where otherwise healthy individuals develop unrelenting seizures
      that do not respond to conventional anticonvulsant therapy and may require months
      of therapy with anesthetic drugs. We have described a case of NORSE who
      subsequently developed mesial temporal lobe sclerosis (MTS) and recurrent
      temporal lobe seizures. We discuss the possible pathophysiological mechanisms by
      which refractory seizures may contribute to the development of temporal lobe
      epilepsy (TLE).

PMID- 22953057
TI  - Neocortical temporal lobe epilepsy.
AB  - Complex partial seizures (CPSs) can present with various semiologies, while
      mesial temporal lobe epilepsy (mTLE) is a well-recognized cause of CPS,
      neocortical temporal lobe epilepsy (nTLE) albeit being less common is
      increasingly recognized as separate disease entity. Differentiating the two
      remains a challenge for epileptologists as many symptoms overlap due to
      reciprocal connections between the neocortical and the mesial temporal regions.
      Various studies have attempted to correctly localize the seizure focus in nTLE as
      patients with this disorder may benefit from surgery. While earlier work
      predicted poor outcomes in this population, recent work challenges those ideas
      yielding good outcomes in part due to better localization using improved
      anatomical and functional techniques. This paper provides a comprehensive review
      of the diagnostic workup, particularly the application of recent advances in
      electroencephalography and functional brain imaging, in neocortical temporal lobe
      epilepsy.

PMID- 22953059
TI  - The "natural" history of medically treated temporal lobe epilepsy: what can an
      evidence-based approach tell us?
AB  - We systematically reviewed the literature to describe the "natural" history of
      medically treated temporal lobe epilepsy (TLE). No population-based studies
      recruiting incident cases of TLE irrespective of age exist. Prospective,
      population-based studies were limited to those recruiting only childhood-onset
      TLE or those reporting TLE as a subgroup of cohorts of focal epilepsies. Few
      studies have been performed in the "MRI era" limiting information on natural
      history secondary to specific pathologies. Available data suggests that TLE is
      highly variable, with unpredictable transient remissions and low rates of seizure
      freedom (30 to 50%). Etiology and failure of first and second drug seem to be the
      most important predictors for treatment prognosis. The role of initial
      precipitating injuries remains speculative, as imaging information of related
      events is either missing or conflicting. Prospective cohorts of new-onset TLE
      with long-term followup using advanced MRI techniques, timely EEG recordings, and
      assessments of psychiatric comorbidities are needed.

PMID- 22953060
TI  - A seizure care pathway in the emergency department: preliminary quality and
      safety improvements.
AB  - Aim. To evaluate the utility of a seizure care pathway for seizure presentations
      to the emergency department (ED) in order to safely avoid unnecessary admission
      and to provide early diagnostic and therapeutic guidance and minimize length of
      stay in those admitted. Methods. 3 studies were conducted, 2 baseline audits and
      a 12-month intervention study and prospective data was collected over a 12-month
      period (Nov 2008-09). Results. Use of the Pathway resulted in a reduction in the
      number of epilepsy related admissions from 341 in 2004 to 276 in 2009 (P =
      0.0006); a reduction in the median length of stay of those admittedfrom 4-5 days
      in the baseline audits to 2 days in the intervention study (P <= 0.001); an
      improvement in time to diagnostic investigations such as CT brain, MRI brain and
      Electroencephalography (P <= 0.001, P <= 0.048, P <= 0.001); a reduction in
      readmission rates from 45.1% to 8.9% (P <= 0.001); and an improvement in follow
      up times from a median of 16 weeks to 5 weeks (P < 0.001). From a safety
      perspective there were no deaths in the early discharged group after 12 months
      follow-up. Conclusion. The burden of seizure related admissions through the ED
      can be improved in a safe and effective manner by the provision of a seizure care
      pathway.

PMID- 22953062
TI  - Mitochondria and cytoprotection.

PMID- 22953061
TI  - Physiopathogenetic Interrelationship between Nocturnal Frontal Lobe Epilepsy and
      NREM Arousal Parasomnias.
AB  - Aims. To build up a coherent shared pathophysiology of NFLE and AP and discuss
      the underlying functional network. Methods. Reviewing relevant published data we
      point out common features in semiology of events, relations to macro- and
      microstructural dynamism of NREM sleep, to cholinergic arousal mechanism and
      genetic aspects. Results. We propose that pathological arousals accompanied by
      confused behavior with autonomic signs and/or hypermotor automatisms are
      expressions of the frontal cholinergic arousal function of different degree,
      during the condition of depressed cognition by frontodorsal functional loss in
      NREM sleep. This may happen either if the frontal cortical Ach receptors are
      mutated in ADNFLE (and probably also in genetically not proved nonlesional cases
      as well), or without epileptic disorder, in AP, assuming gain in receptor
      functions in both conditions. This hypothesis incorporates the previous
      "liberation theory" of Tassinari and the "state dissociation hypothesis" of
      Bassetti and Terzaghi). We propose that NFLE and IGE represent epileptic
      disorders of the two antagonistic twin systems in the frontal lobe. NFLE is the
      epileptic facilitation of the ergotropic frontal arousal system whereas absence
      epilepsy is the epileptic facilitation of burst-firing working mode of the
      spindle and delta producing frontal thalamocortical throphotropic sleep system.
      Significance. The proposed physiopathogenesis conceptualize epilepsies in
      physiologically meaningful networks.

PMID- 22953063
TI  - Effect of vitamins a, C, and e supplementation in the treatment of metabolic
      syndrome in albino rats.
AB  - Obesity and metabolic syndrome increase the risk of cardiovascular morbidity and
      mortality. Oxidative stress seems to be involved in the path physiology of
      cardiovascular complications of metabolic syndrome. In this study we investigated
      the effects of vitamins A, C, and E in the management of metabolic syndrome
      traits condition in albino rats fed with high salt diet. The rats were placed on
      8% NaCl diet for 5 weeks and then supplemented with these vitamins for additional
      4 weeks in the presence of salt diet. Supplementation with vitamins significantly
      (P < 0.01 ) decreased blood pressure of the rats as compared with the control.
      Supplementation also significantly (P < 0.05) reduced serum total cholesterol,
      triglyceride, low-density lipoprotein cholesterol, and very-low-density
      lipoprotein cholesterol and increased high-density lipoprotein cholesterol, and
      total antioxidant status as compared with untreated group. The percentage
      protection of the supplemented groups against atherogenesis indicated 55.50 +/-
      3.75%. Percentage weight gain indicated significant positive correlation with
      triglyceride, insulin resistance, and malondialdehyde while total antioxidant
      status and nitric oxide showed significant negative correlation. Salt diet
      significantly (P < 0.05) induced features of metabolic syndrome. The result,
      therefore, indicated strong relationship between obesity and metabolic syndrome
      and underscores the role of these vitamins in the management of metabolic
      syndrome.

PMID- 22953064
TI  - Prehospital medication administration: a randomised study comparing intranasal
      and intravenous routes.
AB  - Introduction. Opioid overdose is an ever-increasing problem globally. Recent
      studies have demonstrated that intranasal (IN) naloxone is a safe and effective
      alternative to traditional routes of naloxone administration for reversal of
      opioid overdose. Aims. This randomised controlled trial aimed to compare the time
      taken to deliver intranasal medication with that of intravenous (IV) medication
      by advanced paramedic trainees. Methods. 18 advanced paramedic trainees
      administered either an IN or IV medication to a mannequin model in a classroom
      based setting. The time taken for medication delivery was compared. End-user
      satisfaction was assessed using a 5-point questionnaire regarding ease of use and
      safety for both routes. Results. The mean time taken for the IN and IV group was
      87.1 seconds and 178.2 seconds respectively. The difference in mean time taken
      was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, P <=
      0.0001). 89% of advanced paramedic trainees reported that the IN route was easier
      and safer to use than the IV route. Conclusion. This study demonstrates that,
      amongst advanced paramedic trainees, the IN route of medication administration is
      significantly faster, better accepted and perceived to be safer than using the IV
      route. Thus, IN medication administration could be considered more frequently
      when administering emergency medications in a pre-hospital setting.

PMID- 22953065
TI  - Characterization of myelomonocytoid progenitor cells with mesenchymal
      differentiation potential obtained by outgrowth from pancreas explants.
AB  - Progenitor cells can be obtained by outgrowth from tissue explants during primary
      ex vivo tissue culture. We have isolated and characterized cells outgrown from
      neonatal mouse pancreatic explants. A relatively uniform population of cells
      showing a distinctive morphology emerged over time in culture. This population
      expressed monocyte/macrophage and hematopoietic markers (CD11b(+) and CD45(+)),
      and some stromal-related markers (CD44(+) and CD29(+)), but not mesenchymal stem
      cell (MSC)-defining markers (CD90(-) and CD105(-)) nor endothelial (CD31(-)) or
      stem cell-associated markers (CD133(-) and stem cell antigen-1; Sca-1(-)). Cells
      could be maintained in culture as a plastic-adherent monolayer in culture medium
      (MesenCult MSC) for more than 1 year. Cells spontaneously formed sphere clusters
      "pancreatospheres" which, however, were nonclonal. When cultured in appropriate
      media, cells differentiated into multiple mesenchymal lineages (fat, cartilage,
      and bone). Positive dithizone staining suggested that a subset of cells
      differentiated into insulin-producing cells. However, further studies are needed
      to characterize the endocrine potential of these cells. These findings indicate
      that a myelomonocytoid population from pancreatic explant outgrowths has
      mesenchymal differentiation potential. These results are in line with recent data
      onmonocyte-derivedmesenchymal progenitors (MOMPs).

PMID- 22953066
TI  - A comparison of the effectiveness of surgical and nonsurgical treatment of legg
      calve-perthes disease: a review of the literature.
AB  - Legg-Calve-Perthes disease (LCPD) is a degenerative condition of the hip joint
      characterised by idiopathic avascular necrosis of the femoral head. Loss of bone
      mass causes a degree of collapse of the joint and may result in deformity of the
      ball of the femur and the surface of the hip socket. A reduction in hip joint
      range of motion, alternation in growth of femoral head, and associated pain are
      most important problems associated with this disease. Various treatment methods
      are currently in use and aim to increase containment of the femoral head within
      the acetabulum, redistribute loading patterns applied to the femoral head, and to
      decrease the final deformities associated with this condition. These treatments
      depend on a variety of underlying factors and the aim of this paper was to
      determine appropriate pathways for treatment and the evidence of treatment method
      success. A review of the relevant literature was carried out in a variety of data
      bases including PubMed and ISI Web of Knowledge, and Gale between 1950 and 2011.
      Research results were categorised depending on the identified treatment method.
      The success of each treatment pathway was assessed and reasons for the pathway
      selected were grouped by the age of disease onset, follow-up period, and the
      final outcome. Evidence relating to the effectiveness of the treatment method
      used was conflicting. Different methods of screening and follow-up periods were
      employed in each study which used subjects of varying ages. Minimal evidence of
      sufficient quality exists in the literature to determine the most appropriate
      treatment of Legg-Calve-Perthes disease. Research provides some evidence to
      suggest that nontreatment may be as effective as orthotic or surgical
      intervention. More research is required to determine the effectiveness of
      orthotic and surgical treatment.

PMID- 22953067
TI  - Unusual perioperative cardiac emergency in a healthy young woman.
AB  - Serious cardiac complications occurring during noncardiac surgery in a young and
      otherwise normal person can be quite alarming for the anesthesiologist. We report
      here the case of a young, healthy woman who immediately after an uncomplicated
      spinal surgery developed a clinical picture suggestive of an acute myocardial
      infarction (MI) with positive relevant investigations. However, she had an abrupt
      and full clinical recovery and complete normalization of her cardiac
      investigations within a few days of this event and thereafter continued to lead a
      normal, symptom-free life unlike the usual course in an MI; her coronary
      angiography was also normal. A diagnosis of perioperative stress-induced
      cardiomyopathy or Takotsubo cardiomyopathy was subsequently made. This condition
      is characterized by a rapid, severe, but reversible, cardiac dysfunction
      triggered by physical or mental stress. Awareness of this entity should help
      anesthesiologists manage better this infrequent, but potentially life
      threatening, perioperative complication.

PMID- 22953068
TI  - Impossible airway requiring venovenous bypass for tracheostomy.
AB  - The elective surgical airway is the definitive management for a tracheal stenotic
      lesion that is not a candidate for tracheal resection, or who has failed multiple
      tracheal dilations. This case report details the management of a patient who has
      failed an elective awake tracheostomy secondary to the inability to be intubated
      as well as severe scar tissue at the surgical site. A combination of regional
      anesthesia and venovenous bypass is used to facilitate the surgical airway
      management of this patient. Cerebral oximetry and a multidisciplinary team
      approach aid in early detection of an oxygenation issue, as well as the emergent
      intervention that preserved this patient's life.

PMID- 22953069
TI  - An interdisciplinary approach for rehabilitating a patient with amelogenesis
      imperfecta: a case report.
AB  - Amelogenesis imperfecta (AI) has been defined as a group of hereditary enamel
      defects. It can be characterized by enamel hypoplasia, hypomaturation, or
      hypocalcification of the teeth. AI may be associated with some other dental and
      skeletal developmental defects. Restoration for patients with this condition
      should be oriented toward the functional and esthetic rehabilitation. This
      clinical report describes the oral rehabilitation of a young patient diagnosed
      with the hypoplastic type of AI in posterior teeth and hypomatured type of AI in
      anterior teeth.

PMID- 22953070
TI  - A case of unifocal eosinophilic granuloma of the mandible in an adult female: a
      case report.
AB  - Eosinophilic granuloma of bone is a disease with an incidence of one new case per
      350,000 to 2 million per year, which is an uncommon disease of maxillofacial
      region, and presents in more than 90% in children under the age of ten with
      predominance for males. As a result, eosinophilic granuloma of the jaw is always
      unconsidered in the differential diagnosis of similar lesions by many clinicians.
      It is difficult to make a correct diagnosis on it without proof of a pathological
      diagnosis, which correlates with the diverse clinical and radiographic
      presentations of eosinophilic granuloma in the jaws. In the present paper we
      report a rare case of unifocal eosinophilic granuloma of mandible occurring in an
      adult female.

PMID- 22953071
TI  - Persistent Hiccups-An Unusual Presentation of Bilateral Pheochromocytoma without
      Syndromic Association: A Case Report.
AB  - Pheochromocytoma is a rare catecholamine-producing tumor arising from chromaffin
      tissue in the adrenal medulla, occurring in less than 0.2 percent of patients
      with hypertension. The mean age at diagnosis is about 40 years. Pheochromocytomas
      are commonly inherited as features of multiple endocrine neoplasia type 2 or
      several other pheochromocytoma-associated syndromes and have variable clinical
      presentation. Among the presenting symptoms, episodes of palpitations, headaches,
      and profuse sweating are typical and constitute a classic triad. We report a case
      of a 17-year-old male patient with rare bilateral pheochromocytoma presenting
      with persistent hiccups for 4 months and blurring of vision for 1 week, later
      followed by hypertensive crisis. There was neither family history of
      pheochromocytoma nor any classic symptoms. Patient was diagnosed with bilateral
      pheochromocytoma without any syndromic association. But still this patient needs
      to be followed for future development of medullary carcinoma of thyroid because
      it could be an initial presentation of MEN 2A/2B/VHL syndromes. Our paper
      highlights the importance of maintaining a high level of suspicion for persistent
      hiccups and careful clinical screening for hypertension even in absence of
      associated syndromes of pheochromocytoma and classical symptoms to achieve prompt
      diagnosis and to avoid improper management.

PMID- 22953072
TI  - Effect of prolonged discontinuation of L-thyroxine replacement in a child with
      congenital hypothyroidism.
AB  - When diagnosed through neonatal screening and treated promptly and adequately,
      infants with congenital hypothyroidism (CH) experience normal physical growth and
      neurological development. Here we present a 3-year-old boy diagnosed with CH as a
      newborn, who was subsequently left untreated and experienced significant growth
      failure and developmental delay. This case emphasizes the importance of a
      consistent adherence to treatment in preventing such complications, especially in
      infancy and early childhood.

PMID- 22953073
TI  - Iodine Content and Distribution in Thyroid Specimens from Two Patients with
      Graves' Disease Pretreated with Either Propylthiouracil or Stable Iodine:
      Analysis Using X-Ray Fluorescence and Time-of-Flight Secondary Ion Mass
      Spectrometry.
AB  - Patients with Graves' disease can be medically prepared before surgery in
      different ways, which may have various effects on iodine stores. Thyroid
      specimens were collected at surgery from two patients pretreated with
      propylthiouracil (PTU) and stable iodine, respectively. A quantitative analysis
      of iodine content was performed using X-ray fluorescence (XRF) in frozen tissue
      and a qualitative analysis of aldehyde-fixed material with Time-of-Flight
      Secondary Ion Mass Spectrometry (TOF-SIMS). Iodine concentrations were 0.9 mg/mL
      and 0.5 mg/mL in the thyroid tissue from the patients treated with PTU and stable
      iodine respectively. TOF-SIMS showed iodine in the follicle lumina in both.
      However, in the PTU case, iodine was also seen within the thyrocytes indicating
      accumulation of iodinated compounds from uninhibited hormone release. XRF and TOF
      SIMS can be used to follow iodine distribution within the thyroid and the
      intricate processes following the different medical treatment alternatives in
      Graves' disease.

PMID- 22953075
TI  - Xanthoma of bone: a case report.
AB  - Bone xanthoma is a rare disease due to the presence of cholesterol deposits in
      the bone. We report a case of a 56-year-old patient who was hospitalized in
      orthopedic department for fracture on the left humerus. Histological examination
      of bone biopsy performed at this site has objectified cholesterol deposits.
      Laboratory tests showed hypercholesterolemia with hypertriglyceridemia. The
      diagnosis of bone xanthoma was selected. The fracture was treated surgically. An
      initial bone scan revealed bone lesions localized especially at the humerus and
      femur. The patient was put under fenofibrate and statins. The evolution was
      marked by gradual regression of lesions in bone scans of control.

PMID- 22953074
TI  - Carbimazole induced pleural effusion: a case report.
AB  - Objective. To describe a patient with unilateral exudative pleural effusion that
      developed after commencement of carbimazole. Methods. We describe the
      presentation and clinical journey of an elderly woman who presented to the chest
      physicians initially with pleural effusion but was followed up by the
      endocrinology team. Result. The patient was a 77-year-old Caucasian woman who
      presented with symptoms of breathlessness and a confirmed unilateral pleural
      effusion while being on treatment for thyrotoxicosis. Her symptoms needed
      recurrent hospital admission for investigations and drainage, but no potential
      cause was identified after extensive investigations. A drug-induced exudative
      effusion consequent to carbimazole intake was diagnosed as discontinuation of the
      drug lead to complete resolution of the effusion with no recurrence. Conclusion.
      Physicians and Endocrinologist must bear in mind that this potentially rare
      complication of carbimazole while treating patients of thyrotoxicosis as
      appearance of similar features in their patients while being on carbimazole
      should lead to the discontinuation of the drug, and alternative treatment
      strategy should be considered.

PMID- 22953076
TI  - A novel two-step approach for retrieval of an impacted biliary extraction basket.
AB  - Biliary extraction baskets are a commonly used instrument for the removal of
      choledocholithiasis in endoscopic retrograde cholangiopancreatography (ERCP).
      Impaction of the extraction basket is a recognized complication of ERCP, and is
      usually the result of discrepancy between the size of bile duct stone and the
      diameter of the distal bile duct. Whilst mechanical lithotriptors can be used to
      crush the stone or break the wires of the basket to allow its release, failure of
      the lithotriptor device can occur. We describe the case of a 59-year-old
      gentleman who had an ERCP performed for choledocholithiasis. Basket impaction was
      encountered, and the mechanical lithotriptor failed to dislodge the stone/basket
      complex. A two-step technique involving balloon dilatation and forceps
      manipulation of the basket was applied to successfully dislodge the impacted
      basket. We believe this simple and safe technique should be adopted to rescue
      impacted biliary extraction baskets to avoid the need for potential surgical
      removal.

PMID- 22953077
TI  - Prekallikrein deficiency presenting as recurrent cerebrovascular accident: case
      report and review of the literature.
AB  - We report the case of a woman with history of hypertension and hyperlipidemia
      presenting with recurrent episodes consistent clinically with cerebrovascular
      accidents (CVA), and MRI changes suggestive of ischemia versus vasculitis as
      their cause. No anatomical neurological, rheumatic, cardioembolic, or
      arteriosclerotic etiologies could be determined by extensive workup.
      Incidentally, the patient was found to have prolonged activated Partial
      Thromboplastin Time (aPTT) and a normal Prothrombin Time (PT); further testing
      revealed a prekallikrein deficiency. Since no other cause for the CVAs was
      established, and other prothrombotic states were ruled out, it is proposed that
      they are clinical manifestations derived from the prekallikrein deficiency, which
      in a patient with known cardiovascular risk factors could lead to thrombotic
      complications such as stroke.

PMID- 22953078
TI  - Thrombotic microangiopathy with skin localization secondary to cytarabine
      daunorubicin association: report of a case.
AB  - The thrombotic microangiopathy is a syndrome characterized by the combination of
      mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of
      variable severity. In addition to the idiopathic form, several cases are
      identified as secondary to pregnancy, infections, disease systems, organ
      transplants, and cancer. Other forms are secondary to drugs including
      antimitotics. We report the case of a patient followed for acute myelogenous
      leukemia. She received induction chemotherapy combining daunorubicin and
      cytarabine, complicated by thrombotic thrombocytopenic purpura.

PMID- 22953079
TI  - Acute appendicitis in a man undergoing therapy for mantle cell lymphoma.
AB  - A 71-year-old man was diagnosed with an aggressive mantle cell lymphoma and was
      started on six cycles of R-CHOP chemotherapy. Approximately two weeks after
      starting his first cycle of chemotherapy, he complained of severe right lower
      quadrant abdominal pain, and an abdominal CT scan demonstrated an enlarged
      appendix with evidence of contained perforation. The man underwent open
      appendectomy for acute appendicitis and recovered. The appendectomy specimen was
      submitted for routine pathological analysis. There was histologic evidence of
      perforation in association with an inflammatory infiltrate with fibrin adhered to
      the serosal surface; scattered small lymphoid aggregates were present on the
      mucosal surface. Although the lymphoid aggregates in the submucosa and lamina
      propria were rather unremarkable by routine histologic examination,
      immunohistochemistry revealed the lymphocytes to be predominantly Cyclin D1
      overexpressing B cells. To our knowledge, this is the first reported case of
      acute appendicitis in association with appendiceal involvement by mantle cell
      lymphoma.

PMID- 22953081
TI  - Systemic Capillary Leak Syndrome as an Initial Presentation of ALK-Negative
      Anaplastic Large Cell Lymphoma.
AB  - Systemic capillary leak syndrome (SCLS) is a rare disease characterized by third
      spacing of plasma into the extravascular compartment, leading to anasarca,
      hemoconcentration, and hypovolemic shock. It has been rarely associated with
      lymphomas, and reports usually indicate that it occurs after antineoplastic
      treatment. We present the case of a patient with ALK-negative anaplastic large
      cell lymphoma who presented with SCLS as the initial manifestation of her
      lymphoma. The SCLS resolved with treatment of the malignancy with steroids and
      chemotherapy.

PMID- 22953080
TI  - Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and
      Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the
      Literature.
AB  - Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has
      the lowest incidence amongst the chronic myeloproliferative neoplasms and is
      characterized by a rather short median survival and a risk of progression to
      acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a
      terminal event. As observed with other chronic myeloproliferative neoplasms, the
      bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive
      in nature. In our paper, we present a 70-year-old Caucasian male who was
      diagnosed with primary myelofibrosis, and after 8 years of followup and therapy
      developed an AML. The small lymphoid aggregates noted in his bone marrow were
      neoplastic in nature and represented bone marrow involvement by a CD5-negative
      mantle cell lymphoma (MCL) that presented without any associated lymphadenopathy.
      We reviewed the English medical literature to identify a single case report of
      simultaneous association of AML and a MCL in the bone marrow. The unusual
      association presented here suggests an increase in observer awareness to
      apparently benign lymphoid aggregates in chronic myeloproliferative neoplasms.

PMID- 22953082
TI  - Rituximab-induced coronary vasospasm.
AB  - Rituximab has improved the treatment of B-cell non-Hodgkin lymphomas. While it is
      generally well tolerated, serious adverse effects including infusion reactions
      with hemodynamic compromise and cardiac arrhythmias or ischemia are possible. We
      report a case of coronary vasospasm occurring during a rituximab infusion in a
      patient with minimal tumour burden and who had no cardiac risk factors. This case
      highlights that determination of the cause of ischemia is important and may
      identify some patients who can be successfully rechallenged.

PMID- 22953083
TI  - Severe Isospora (Cystoisospora) belli Diarrhea Preceding the Diagnosis of Human T
      Cell-Leukemia-Virus-1-Associated T-Cell Lymphoma.
AB  - Isospora (Cystoisospora) belli diarrhea can sometimes be fulminant in
      immunocompromised patients. It is endemic in tropical and subtropical areas, and
      sporadic episodes have been reported in nonendemic areas in nursing homes, day
      care centers, and psychiatric institutions. We describe isosporiasis in an HIV
      negative Sudanese-American female who presented with a debilitating diarrheal
      illness and profound weight loss. Isospora belli was detected in her stool by
      modified acid-fast staining. Serologic testing was negative for HIV but positive
      for HTLV-1 infection. Treatment with TMP-SMZ led to improvement in her diarrhea
      which recurred after stopping antibiotics. Subsequently, she developed
      generalized lymphadenopathy which was diagnosed as ATLL on immunohistochemical
      staining. Chemotherapy was initiated, but her condition continued to worsen due
      to persistent diarrhea and resulting profound electrolyte abnormalities. The
      patient opted for comfort measures and died a few weeks later at a nursing
      facility. This case emphasizes that the detection of I. belli should trigger
      testing for HIV, HTLV-1, and other causes of immunocompromise. We suggest that
      treatment with TMP-SMZ should be initiated and continued for a prolonged period
      of time in immunocompromised patients with I. belli diarrhea.

PMID- 22953084
TI  - Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A
      Reminder of the Phenomenon of Apparent Vaccine Failure.
AB  - We present two cases of bacterial meningitis caused by Haemophilus influenzae
      type b (Hib) which developed a few days after conjugate Hib vaccination. This
      phenomenon of postimmunization provocative time period is reviewed and discussed.
      These cases serve as a reminder to clinicians of the risk, albeit rare, of
      invasive Hib disease in the short period after successful immunization.

PMID- 22953085
TI  - Acute sinusitis resulting in a craniotomy: an uncommon complication of a common
      infection.
AB  - Acute bacterial sinusitis is a common infectious condition. Patients may
      initially present with an uncomplicated infection and later, despite appropriate
      initial antibiotic therapy, develop a potentially life-threatening complication.
      Interventions aimed at alleviating such unexpected events need be prompt and
      adequate. We describe a case of a patient who initially presented with signs and
      symptoms of acute sinusitis later to be diagnosed with a frontal epidural
      abscess.

PMID- 22953086
TI  - Neuroleptic malignant syndrome caused by a combination of carbamazepine and
      amitriptyline.
AB  - A 32-year-old female, with a history of secondarily-generalized convulsive
      epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic
      malignant syndrome while receiving carbamazepine and amitriptyline concurrently.
      We hypothesize that the addition of amitriptyline to carbamazepine caused a
      decrease in the serum level of carbamazepine, resulting in NMS. We conclude that
      combination therapy with carbamazepine and amitriptyline should be avoided in
      patients who are predisposed to NMS. The purpose of this paper is to warn
      physicians against combination therapy with carbamazepine and tricyclic
      antidepressants which may be conducive to neuroleptic malignant syndrome in
      susceptible patients.

PMID- 22953087
TI  - EEG suppression associated with apneic episodes in a neonate.
AB  - We describe the EEG findings from an ex-preterm neonate at term equivalent age
      who presented with intermittent but prolonged apneic episodes which were presumed
      to be seizures. A total of 8 apneic episodes were captured (duration 23-376
      seconds) during EEG monitoring. The baseline EEG activity was appropriate for
      corrected gestational age and no electrographic seizure activity was recorded.
      The average baseline heart rate was 168 beats per minute (bpm) and the baseline
      oxygen saturation level was in the mid-nineties. Periods of complete EEG
      suppression lasting 68 and 179 seconds, respectively, were recorded during 2 of
      these 8 apneic episodes. Both episodes were accompanied by bradycardia less than
      70 bpm and oxygen saturation levels of less than 20%. Short but severe episodes
      of apnea can cause complete EEG suppression in the neonate.

PMID- 22953088
TI  - Unusual forehead tremor in four patients with essential tremor.
AB  - Forehead tremor has only been reported in two patients with essential tremor, one
      with rhythmic tremor and the other with dystonic tremor. We report 4 new patients
      with essential tremor who present a 4-6 Hz frontal tremor registered by
      electromyography and unusual features like frontal tremor preceding limb tremor
      or unilateral involvement. Frontal tremor is present in some patients with
      essential tremor, sometimes preceding limb tremor. Treatment with botulinum toxin
      may be useful.

PMID- 22953089
TI  - Takotsubo-like myocardial dysfunction accompanied with cerebellar hemorrhage.
AB  - We report a 71-year-old woman with takotsubo-like myocardial dysfunction
      accompanied with cerebellar hemorrhage. On admission time, although she was
      unconscious by cerebellar hemorrhage, no obvious heart failure and serological
      disorder were observed. Three days later, operation for extraventricular drainage
      was performed. However, conscious level did not change. Four days after
      admission, the change of electrocardiogram wave pattern and the decrement of
      heart wall motion were detected. These findings revealed takotsubo-like
      myocardial dysfunction had occurred. Physical stresses by cerebellar hemorrhage
      and cranial operation might cause cardiac disorder. This is a remarkable case of
      takotsubo-like myocardial dysfunction, which is brought about cerebellar
      hemorrhage against subarachnoid hemorrhage.

PMID- 22953090
TI  - Chorea as the first sign in a patient with elderly-onset systemic lupus
      erythematosus.
AB  - The case of an elderly patient who had chorea as an initial symptom of systemic
      lupus erythematosus (SLE) accompanied by antiphospholipid syndrome (APS) is
      reported. A 68-year-old woman suddenly developed chorea of her left arm and leg.
      Magnetic resonance imaging (MRI) of the brain demonstrated a focal lesion in the
      right caudate head, which showed hyperintensity on fluid-attenuated inversion
      recovery and diffusion-weighted imaging. This condition was thought to be a
      common form of vascular chorea, which is likely to occur in elderly individuals;
      however, the laboratory data of this patient finally fulfilled the diagnostic
      criteria of SLE and APS. Physicians should be careful in diagnosing elderly
      individuals simply as having a vascular chorea because this symptom can be the
      initial manifestation of SLE or APS.

PMID- 22953091
TI  - Feasibility of Functional Electrical Stimulation-Assisted Neurorehabilitation
      following Stroke in India: A Case Series.
AB  - Functional Electrical Stimulation (FES) facilitates ambulatory function after
      paralysis by electrically activating the muscles of the lower extremities. The
      Odstock Dropped Foot Stimulator (ODFS, Odstock, UK) called ODFS Pace, was used
      for heel-switch triggered FES-assisted walking. The ODFS is recommended as an
      intervention for neurologically impaired gait in the Royal College of Physicians
      (UK) Clinical Guidelines on Stroke. Based on the guidelines by the National
      Institute of Clinical Excellence (NICE, UK), we started first clinical study in
      India on ODFS Pace as an orthotic intervention for daily use. In this preliminary
      study, we also investigated improvement in volitional walking following 6
      sessions (3 times per week, for 2 weeks) of 30 minutes of FES-assisted treadmill
      walking on 7 chronic (>6 months after stroke) stroke survivors. We found that
      short-duration, moderately intensive FES-assisted gait therapy improved
      volitional gait in 3 out of 7 stroke survivors suffering from foot drop. Even in
      absence of improvement in volitional walking, there were no adverse effects and
      the subjects found heel-switch triggered FES-assisted walking mostly "easy" (6
      out of 7). Therefore FES is promising as an orthotic intervention for daily use;
      however, tailoring the intensity and/or frequency based on patient's ability may
      make it viable as a therapeutic intervention.

PMID- 22953092
TI  - Interferon Beta-1a Improves Urinary Symptoms, Reduces Proviral Load, and Modifies
      the Immune Response in a Patient with HAM/TSP.
AB  - The human T-cell lymphotropic virus type 1 (HTLV-1) is the known causative agent
      of a chronic neurologic condition known as HTLV-1-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP). Although several therapies have been evaluated for
      HAM/TSP, none have been approved for use in humans. In this paper, we describe a
      55-year-old female patient with HAM/TSP who was treated with interferon beta-1a.
      This patient, in comparison to 20 female patients with HAM/TSP who were not
      treated, showed improvement in urinary symptoms over four years of therapy, as
      well as a reduction in HTLV-1 proviral load and serum cytokine levels typically
      observed in HAM/TSP. This improved outcome merits further controlled studies on
      the use and efficacy of interferon beta-1a as a therapy for HAM/TSP.

PMID- 22953093
TI  - Mullerian adenosaroma of the cervix with sarcomatous overgrowth and heterologous
      elements presenting as a recurrent cervical polyp.
AB  - Mullerian adenosarcoma of the cervix is a rare tumor composed of benign
      epithelial and malignant stromal components. Sarcomatous overgrowth and
      heterologous elements in cervical adenosarcoma are extremely infrequent. We
      report the case of a 26-year-old woman admitted at the gynaecology department for
      a painless mass protruding from her vagina. The initial pathological exam
      concluded to endocervical polyp. Six months later, the patient was readmitted
      with a recurrence of the polyp. The pathological exam demonstrated interlacing
      fascicles of elongated spindle cells with few mitotic activity and no glandular
      formation. After reviewing of the initial polyp the diagnosis of mullerian
      adenosarcoma was suggested. A second recurrence of the polyp was noted one month
      later. Histopathological exam of the recurrent polyp confirmed the diagnosis of
      adenosarcoma with sarcomatous overgrowth and heterologous elements. The patient
      was lost for follow-up. Cervical adenosarcoma with sarcomatous overgrowth and
      heterologous element is a rare tumor that occurs in younger age in contrast to
      endometrium/corpus uterin mullerian adenosarcoma. In young women with recurrent
      cervical polyp, mullerian adenosarcoma must be considered and should be excluded
      by careful histopathological exam. Sarcomatous overgrowth and myometrial invasion
      are the most important prognostic factors. Treatment strategy is still unclear.

PMID- 22953094
TI  - A case of brain metastases from breast cancer treated with whole-brain
      radiotherapy and eribulin mesylate.
AB  - Patients with triple receptor-negative breast cancer often develop aggressive
      metastatic disease, which also might involve the brain. In many cases, systemic
      and local treatment is needed. It is important to consider the toxicity of chemo-
      and radiotherapy, especially when newly approved drugs become available.
      Randomised studies leading to drug approval often exclude patients with newly
      diagnosed brain metastases. Here we report our initial experience with eribulin
      mesylate and whole-brain radiotherapy (WBRT) in a heavily pretreated patient with
      multiple brain, lung, and bone metastases from triple receptor-negative breast
      cancer. Eribulin mesylate was given after 4 previous lines for metastatic
      disease. Two weeks after the initial dose, that is, during the first cycle, the
      patient was diagnosed with 5 brain metastases with a maximum size of
      approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT
      with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was
      discontinued because of newly diagnosed liver metastases and progression in the
      lungs. No unexpected acute toxicity was observed. The only relevant adverse
      reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL,
      leukocytes 3.1 * 10(9)/L). The patient died from respiratory failure 18.5 months
      from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain
      metastases. To the best of our knowledge, this is the first report on combined
      WBRT and eribulin mesylate.

PMID- 22953095
TI  - Langerhans cell histiocytosis of the cranial base: is low-dose radiotherapy
      effective?
AB  - Introduction. Langerhans cell histiocytosis (LCH) is a rare disease of unknown
      etiology with different clinical features. A standardised treatment has not been
      established so far. Case Report. We report a case of a 28-year-old patient who
      initially presented with hypesthesia of the fifth cranial nerve and pain of the
      left ear. Diagnosis showed a tumour localised in the cranial base with a maximum
      diameter of 4.1 cm. The diagnosis of LCH was confirmed histologically by biopsy.
      Diagnostic workup verified the cranial lesion as the sole manifestation of LCH. A
      total dose of 9 Gy (single dose 1.8 Gy) was delivered. The symptoms dissolved
      completely within 6 months after radiation; repeated CT and MRI scans revealed a
      reduction in size of the lesion and a remineralisation of the bone. After a
      followup of 13 years the patient remains free of symptoms without relapse or any
      side effects from therapy. Discussion. Due to the indolent course of the disease
      with a high rate of spontaneous remissions the choice of treatment strongly
      depends on the individual clinical situation. In the presented case low-dose
      radiotherapy was sufficient to obtain long-term local control in a region with
      critical structures and tissues.

PMID- 22953096
TI  - Wegener's granulomatosis with extensive bone abnormalities mimicking fungal
      sinusitis.
AB  - Abnormalities of the underlying bone of the paranasal sinuses have sometimes been
      shown in Wegener's granulomatosis (WG). We describe an interesting case of WG
      with extensive bone abnormalities in the sinuses mimicking fungal sinusitis. A 30
      year-old woman presented with intermittent unilateral epistaxis. Biopsy was
      performed for the granulation tissue in the right nasal cavity, and she was
      diagnosed as having WG. Computed tomography (CT) revealed a ring-like
      calcification, mimicking a fungus ball, in the right maxillary sinus. Endoscopic
      sinus surgery was performed to confirm the diagnosis. A spherical bony structure,
      surrounded by granulation tissue, was identified in the maxillary sinus. The wall
      of the "bony ball" was fragile, like an egg shell. No fungus was found in the
      sinus. Thus, the extensive bone abnormalities were due to WG.

PMID- 22953097
TI  - A rare case of survival after complete traumatic cricotracheal separation.
AB  - We report the survival of an extremely rare case of complete cricotracheal
      transection following incisional trauma with knife. The clinical record
      underlines the importance of prompt airway management and immediate neck
      exploration in such cases. To the authors knowledge, such a case has not been
      reported previously in the literature.

PMID- 22953098
TI  - Dysphagia due to Diffuse Idiopathic Skeletal Hyperostosis.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is usually asymptomatic. However,
      rarely, it causes dysphagia, hoarseness, dyspnea, snoring, stridor, and laryngeal
      edema. Herein, we present a patient with DISH causing dysphagia. A 70-year-old
      man presented with a 4-month history of sore throat, dysphagia, and foreign body
      sensation. Flexible laryngoscopy revealed a leftward-protruding posterior wall in
      the hypopharynx. Computed tomography and magnetic resonance imaging revealed a
      bony mass pushing, anteriorly, on the posterior hypopharyngeal wall. Ossification
      included an osseous bridge involving 5 contiguous vertebral bodies. Dysphagia due
      to DISH was diagnosed. His symptoms were relieved by conservative therapy using
      anti-inflammatory drugs. However, if conservative therapy fails and symptoms are
      severe, surgical treatments must be considered.

PMID- 22953099
TI  - A case of radiation-induced multifocal laryngeal angiosarcoma presenting as a
      diagnostic dilemma.
AB  - Head and neck sarcomas are relatively rare tumors, with angiosarcomas
      representing a small subset. Angiosarcoma is a malignant endothelial neoplasm
      characterized by atypical, multilayered, or solid endothelial proliferation with
      vasoformative architecture. The global incidence of irradiation-associated
      sarcoma is estimated as between 0.03% and 0.08%. Here we reported the case of an
      elderly woman previously treated with radiation more than 20 years ago for an
      unknown primary of head and neck. This interesting case presented as a diagnostic
      challenge, and multiple biopsies were required to eventually establish the
      diagnosis of laryngeal angiosarcoma. We additionally have confirmation from our
      prior radiation records that the patient did, in fact, receive a substantial dose
      of radiation to the site previously. To our knowledge, this case represents the
      first report of a documented radiation-induced multifocal laryngeal angiosarcoma.

PMID- 22953100
TI  - Congenital tongue base cyst presenting with laryngeal stridor in youth: a case
      report.
AB  - Introduction. Tongue base cyst is an uncommon but potentially dangerous cause of
      stridor in neonates and infants. Case Presentation. We report a case of a 2-month
      old Arabic male infant with a congenital tongue base cyst revealed by inspiratory
      stridor and recurrent respiratory distress. Diagnosis of cyst was suspected at
      endoscopy and confirmed by MRI imaging. The cyst was marsupialized with CO(2)
      laser. One year later, the child remains asymptomatic without recurrence of the
      mass. Conclusion. Tongue base cysts should be considered in differential
      diagnosis in new borns with stridor, respiratory difficulties, or swallowing
      problems. Definitive therapy requires large marsupialization under general
      anesthesia.

PMID- 22953101
TI  - Papillary endolymphatic sac tumor: a case report.
AB  - Glandular tumors involving the middle ear are rare and distinguishing between
      adenoma and adenocarcinoma remains difficult. A distinct subclass of these tumors
      demonstrates microscopic papillary architecture and has a propensity to erode the
      petrous bone and extend intracranially. The term "aggressive papillary middle ear
      tumor" has recently been proposed to describe this more invasive type of middle
      ear tumor. These tumors cause symptoms even when microscopic in size. Although
      histologically benign, they have been locally destructive with frequent
      intracranial extension and patients may die of uncontrolled local disease. These
      tumors do not metastasize but there is single case report of drop metastasis to
      the spine in the literature. Hence this tumor must be distinguished from other
      benign tumors of the middle ear. These rare neoplasms constitute a distinct
      pathological entity and deserve wider recognition.

PMID- 22953102
TI  - Sensorineural Hearing Loss due to Air Bag Deployment.
AB  - Deployment of the air bag in a passenger vehicle accident rarely causes otologic
      injuries. However, sensorineural hearing loss induced by air bag deployment is
      extremely rare, with only a few cases reported in the English literature. A 38
      year-old man involved in a traffic accident while driving his car at 40 km/hour
      presented with right sensorineural hearing loss and tinnitus, without associated
      vertigo. Pure-tone audiometry demonstrated elevated thresholds of 30 dB and 25 dB
      at 4 kHz and 8 kHz, respectively, on the right side. Air bag deployment in car
      accidents is associated with the risk of development of sensorineural hearing
      loss.

PMID- 22953103
TI  - Bilateral endoscopic medial maxillectomy for bilateral inverted papilloma.
AB  - Inverted papilloma (IP) is a benign tumor of the nasal cavity and paranasal
      sinuses that is unilateral in most cases. Bilateral IP, involving both sides of
      the nasal cavity and sinuses, is extremely rare. This paper describes a large IP
      that filled in both sides of the nasal cavity and sinuses, mimicking association
      with malignancy. The tumor was successfully treated by bilateral endoscopic
      medial maxillectomy (EMM). The patient is without evidence of the disease 24
      months after surgery. If preoperative diagnosis does not confirm the association
      with malignancy in IP, endoscopic sinus surgery (ESS) should be selected, and
      ESS, including EMM, is a good first choice of the treatment for IP.

PMID- 22953104
TI  - Posttraumatic cholesteatoma complicated by a facial paralysis: a case report.
AB  - The posttraumatic cholesteatoma is a rare complication of different types of the
      temporal bone damage. Its diagnosis is often done after several years of
      evolution, sometimes even at the stage of complications. A case of posttraumatic
      cholesteatoma is presented that was revealed by a facial nerve paralysis 23 years
      after a crash of the external auditory canal underlining the importance of the
      otoscopic and radiological regular monitoring of the patients with a traumatism
      of the temporal bone.

PMID- 22953105
TI  - Xanthogranuloma of the external auditory canal mimicking a benign tumor: a case
      report.
AB  - Exostosis, osteoma, and adenoma are the most commonly encountered benign lesions
      in the external auditory canal. Herein, we report a case of the mass arising from
      the external auditory canal in a 24-year-old Japanese man. CT revealed the soft
      tissue mass without bony erosion, and MRI revealed that the mass showed a
      homogenous, iso signal intensity on a both T1- and T2-weighted image, suggesting
      that the mass is a benign tumor such as adenoma. Pathological examination showed
      that the specimen demonstrated xanthogranuloma in the external auditory canal.
      Although xanthogranuloma of the external auditory canal is extremely rare,
      otolaryngologists should recognize this condition during the inspection of the
      external auditory canal.

PMID- 22953106
TI  - Plasma cell mucositis of Oro- and hypopharynx: a case report.
AB  - Objective. To raise awareness of plasma cell mucositis as a rare differential
      diagnosis for oral mucosal ulceration and its macroscopic similarity to
      malignancy. Method. We report a patient who presented with oral features
      suggestive of malignancy. A biopsy revealed plasma cell mucositis. Results. The
      patient successfully had a full excision of one lesion and a spontaneous
      resolution of the other. Conclusion. With the increasing incidence of oral
      mucosal pathology, physicians should be aware of this differential diagnosis.

PMID- 22953107
TI  - Capillary hemangioma of the middle ear: one case report and review of the
      literature.
AB  - Hemangiomas are rare benign vascular tumors; there are several types including
      the capillary hemangiomas, we present the case of an exceptional localization of
      capillary hemangioma in the middle ear. We report the case of a 60-year-old
      female which consults for episodes of pulsatile tinnitus, otorragies, and hearing
      loss of the left ear. The clinical examination revealed a reddish polypoid mass
      in the left external auditory canal, the radiological tests showed a vascular
      mass in the middle left ear. The tumor was surgically removed, the histological
      study revealed a capillary hemangioma. The incidence of hemangiomas in the
      temporal bone, especially in the middle ear, is exceptional. Medical imaging
      guides to the vascular nature of these tumors that make confusion with other
      vascular tumors such as tympanic paragangliomas. The management is often surgical
      and the final diagnosis is histological.

PMID- 22953108
TI  - Small cell carcinoma of the larynx treated by concurrent chemoradiotherapy: a
      case report.
AB  - Small cell carcinoma (SmCC) generally occurs in the lung and extrapulmonary SmCC
      is a relatively rare entity. Here, we present a case of a 42-year-old male with
      SmCC of the larynx diagnosed as cT3N0M0. Concurrent chemoradiotherapy using
      cisplatin (CDDP) and etoposide (VP-16) was given, which achieved complete
      response (CR). Lung metastasis became evident in 16 months whereas the
      locoregional control remained good. In spite of intensive chemotherapy using CDDP
      and irinotecan (CPT-11), the patient died of disease in 34 months after the first
      interview. Since the prognosis of laryngeal SmCC is extremely poor, organ
      preservation therapy should be considered instead of radical laryngectomy.

PMID- 22953109
TI  - Symptomatic squamous papilloma of the uvula: report of a case and review of the
      literature.
AB  - Background. Oral squamous papillomas are benign pedunculated masses that grow
      most commonly on the palate. These benign lesions rarely cause symptoms. Methods.
      Here we present the case of a large, elongated squamous papilloma of the uvula
      causing dysphagia. We also review pertinent literature related to these lesions.
      Results. This patient underwent surgical excision of her atypically symptomatic
      oral lesion, with complete resolution of symptoms. Conclusion. Oral squamous
      papillomas are benign lesions which are usually asymptomatic. Dysphagia due to a
      squamous papilloma of the uvula has only been reported once in the literature
      previously. The development of symptoms such as dysphagia due to squamous
      papilloma of the uvula is uncommon; however this may be more likely in the
      presence of particularly large lesions.

PMID- 22953110
TI  - Facial baroparesis caused by scuba diving.
AB  - Middle ear barotrauma is one of the common complications of SCUBA diving
      representing acute otalgia, hearing loss, and bleeding. But occurrence of facial
      palsy is rare. Here we report a case of a 30-year-old navy diver suffered middle
      ear barotrauma with transient facial palsy after SCUBA diving. He felt difficulty
      in equalizing the pressure in middle ear with Valsalva maneuver during diving,
      and suffered right facial palsy and aural fullness after diving. Clinical
      examination showed remarkable bulging of the right tympanic membrane and right
      facial palsy without other neurological findings. But facial palsy was
      disappeared immediately after myringotomy. We considered that the etiology of
      this case was neuropraxia of facial nerve in middle ear caused by over pressure
      of middle ear.

PMID- 22953111
TI  - Thoracic Saccular Aortic Aneurysm Presenting with Recurrent Laryngeal Nerve Palsy
      prior to Aneurysm Rupture: A Prodrome of Thoracic Aneurysm Rupture?
AB  - Left recurrent laryngeal nerve palsy rarely results from cardiac disease. We
      present 2 cases of left recurrent laryngeal nerve palsy caused by thoracic
      saccular aortic aneurysms. One patient suffered an aortic aneurysm rupture one
      month after the advent of hoarseness, necessitating emergency surgery with aortic
      arch replacement. The other patient underwent elective aortic arch replacement
      surgery. Both saccular aortic aneurysms protruded downward in the aortopulmonary
      window to compress the recurrent laryngeal nerves. This is only the 5th case
      report of the rare occurrence of acute recurrent laryngeal nerve palsy subsequent
      to saccular aneurysm rupture in the English literature. Recurrent laryngeal nerve
      palsy does not always indicate imminent aneurysm rupture, but should trigger
      awareness of a potential rupture in the near future. Left recurrent laryngeal
      nerve palsy might be a prodrome of aneurysm rupture.

PMID- 22953112
TI  - Giant fibrolipoma of the esophagus.
AB  - Benign tumors of the esophagus are uncommon, representing <0.5% of esophageal
      tumors. Fibrolipomas are a subset of benign fibrovascular tumors, which present
      with dysphagia, odynophagia, and substernal fullness. These intraluminal tumors
      can become elongated and molded into a long pedunculated polyp by constant
      peristaltic movements. They can cause esophageal obstruction if large and long
      enough and can cause asphyxiation if they become lodged into the glottis. A
      barium swallow is the main diagnostic tool; treatment is surgical via a
      transoral, transcervical, or transthoracic approach. We report the excision of a
      large esophageal fibrolipoma through a transoral laser microsurgical approach.

PMID- 22953113
TI  - Metallic stents for proximal tracheal stenosis: is it worth the risk?
AB  - Objective. To demonstrate the risk associated with blocked proximal tracheal
      stents when a patient presents with acute respiratory distress, with blockage of
      stent and what is the best management we can offer without damage to the stent
      and its associated complications. Case Report. A 22-yr-old, male patient,
      presented in severe respiratory distress. He had history of corrosive poisoning
      for which he was tracheotomised. A stainless steel wire mesh stent was placed in
      the trachea, from the subglottis, to just above the carina. One month later, he
      presented with a critically compromised airway with severe respiratory distress.
      Emergency tracheostomy was done and the metallic stent had to be cut open, in
      order to provide an airway. Conclusion. Management of blocked proximal stents
      with patient in respiratory distress remains a challenge. Formation of
      granulation tissue is common and fibreoptic bronchoscopic assisted intubation may
      not always be possible. A regular follow up of all patients with stents is
      essential. Placement of stents within a few centimetres of cricotracheal junction
      should not be encouraged for long term indications.

PMID- 22953114
TI  - Pleomorphic adenoma of the cervical heterotopic salivary gland: a case report.
AB  - Introduction. Although pleomorphic adenoma is the most common neoplasm of the
      salivary glands, this tumor most commonly involves the minor salivary glands of
      palatal and rarely occurs in cervical region. Case Report. A 21-year-old female
      referred to our clinic due to painless mass of right upper region of neck. After
      paraclinical and pathologic evaluation, it was diagnosed as cervical pleomorphic
      adenoma. Conclusion. Pleomorphic adenoma may be rarely involving the neck.
      Although the prognosis is good, the choice treatment is the complete resection of
      the tumor.

PMID- 22953116
TI  - Descending necrotising mediastinitis: a case report illustrating a trend in
      conservative management.
AB  - The mortality rate from descending necrotising mediastinitis (DNM) has declined
      since its first description in 1938. The decline in mortality has been attributed
      to earlier diagnosis by way of contrast-enhanced computed tomographic (CT)
      scanning and aggressive surgical intervention in the form of transthoracic
      drainage. We describe a case of DNM with involvement of anterior and posterior
      mediastinum down to the diaphragm, managed by cervicotomy and transverse cervical
      drainage with placement of corrugated drains and a pleural chest drain, with a
      delayed mediastinoscopy and mediastinal drain placement. We advocate a
      conservative approach with limited debridement and emphasis on drainage of
      infection in line with published case series.

PMID- 22953115
TI  - Kikuchi-fujimoto disease: a case report and literature review.
AB  - Case. 38-year-old lady was referred to the ENT clinic with history of right-sided
      facial pain, otalgia, and odynophagia. Clinical examination revealed enlarged
      right-sided lymph nodes in the neck. Further radiological scans showed a mass
      near the carotid and enlarged level V lymph nodes. Lymphoma was initially
      suspected. Fine-needle aspiration and excision biopsy were undertaken.
      Histological analysis later suggested Kikuchi-Fujimoto disease, also known as
      histiocytic necrotising lymphadenitis. Literature Review. Kikuchi-Fujimoto
      disease (KFD) was described in 1972 as lymphadenitis with focal proliferation of
      reticular cells accompanied by numerous histiocytes and extensive nuclear debris.
      KFD, frequently found in East Asian countries, is rare in the UK. No definite
      aetiology of KFD is known despite autoimmune and infection factors being
      suggested. The diagnostic hallmark is histological findings from lymph nodes.
      Malignancy should be excluded. This condition is mainly self-limiting; hence,
      management is limited to supportive care. Steroid therapy could be used in severe
      cases. KFD is relatively unknown in the UK and this case report aims to highlight
      its occurrence in our population.

PMID- 22953117
TI  - Cryptococcal tongue lesion in a stem cell transplant patient: first reported
      case.
AB  - A compromised immune system places individuals at a significantly higher risk for
      many infectious processes. Immunosuppression also increases the risk of
      malignancy due to the body's decreased ability to perform its normal
      immunosurveilance and response. It is therefore imperative to have regular
      thorough evaluations of these patients, as slight abnormalities may be the early
      signs of infection or neoplasm. We present the first reported case of a tongue
      lesion in a stem cell transplant patient, highly concerning for malignancy, which
      was found to be a mucocutaneous presentation of disseminated Cryptococcus.

PMID- 22953118
TI  - Extradural dermoid cyst of mastoid bone: a case report.
AB  - Dermoid cysts of the head and neck are rare congenital benign tumors. According
      to the literature they represent about seven percent of all dermoids and less
      than one percent of all intracranial neoplasms. Extradural dermoid cysts are very
      rare. We report a case of intracranial extradural dermoid cyst of mastoid bone.
      We believe that this is the second documented extradural dermoid cyst, the first
      case reported in the literature (Ammirati et al., 2007) was in close relation to
      the petrous apex but ours is in close relation to mastoid antrum. Hearing loss
      was the only clinical presentation in this case, while neurological symptoms were
      the main presenting symptoms in the first reported case. We present our
      management of this rare case with respect to the clinical, radiological,
      histopathological, and surgical aspects and conclude that dermoid tumors, though
      rare, need to be included in differential diagnosis of middle ear lesions.

PMID- 22953119
TI  - Cases of common carotid artery pseudoaneurysm treated by stent graft.
AB  - Common carotid artery (CCA) pseudoaneurysms are rare and potentially lethal, and
      adequate treatment is warranted in order to prevent rupture or neurologic
      sequelae. The causes of CCA pseudoaneurysm include blunt or penetrating trauma,
      infection, and vasculitis, as well as iatrogenic and unknown causes. Previously,
      surgery was the standard treatment for pseudoaneurysm. However, endovascular
      surgical approaches such as stent graft or coiling have become effective
      alternatives with minimal morbidity and high success rates. Here, we report two
      cases of CCA pseudoaneurysms that were successfully treated by stent graft and
      review the current literature.

PMID- 22953120
TI  - Giant cell tumor of the temporal bone with direct invasion into the middle ear
      and skull base: a case report.
AB  - Giant cell tumor (GCT) is classified as a benign bone tumor, and it is frequently
      identified at the epiphysis of long bones and relatively rare in the temporal
      bone. For orthopedists expert at recognizing bone and soft tissue tumors, the
      diagnosis of GCT is relatively easy; however, since head and neck surgeons
      experience few cases of GCT, it may be difficult to diagnose when it occurs in
      the temporal bone. A 32-year-old man complained of left hearing loss, aural
      fullness, and tinnitus. Examination of the ear revealed a bulging tumor.
      Audiologic examination demonstrated conductive hearing loss of the left ear.
      Computer tomograph of the temporal bone showed a soft-tissue-density
      specification indicating bone destruction at the left temporal bone. The tumor
      invaded the skull base. Imaging examinations using magnetic resonance imaging
      revealed a nonhomogenous isosignal intensity area on T1 at the left temporal
      bone. After intravenous gadolinium, the mass showed unequal enhancement. This
      patient subsequently underwent surgery to remove the lesion using transmastoid
      and middle fossa approach. Pathological examinations from specimens of the tumor
      revealed characteristic of GCT. No clinical or radiological evidence of tumor
      recurrence was detected for 4 years.

PMID- 22953121
TI  - A case of typical carcinoid of the larynx.
AB  - We report herein a rare case of typical carcinoid occurring primarily in the
      epiglottis. The patient was a 70-year-old man. On initial examination, a polypoid
      lesion with irregular surface near the center right-hand side of the laryngeal
      surface of the epiglottis was observed, and a biopsy was performed. Pathological
      examination of the specimen suggested the possibility of adenocarcinoma. Surgical
      excision was performed by means of laryngomicrosurgery. A Weerda-type
      laryngoscope was used to open the larynx, supplemented by rigid nasal sinus
      surgery endoscopes, and the right-hand half of the epiglottis were excised was
      ensured using a CO(2) laser. Postoperative pathological diagnosis was negative
      for adenocarcinoma and squamous cell cancer; typical carcinoid was diagnosed
      according to the World Health Organization criteria. Aspiration occurred
      postoperatively, swallowing training was therefore provided, and the patient was
      discharged from hospital 2 months after surgery when he was able to eat normally.
      As of 4 years after surgery, the patient remains under follow-up observation by
      means of PET-CT and neck, thoracic, and abdominal CT administered at appropriate
      intervals, but no findings indicating obvious recurrence or metastasis have been
      observed, and the patient displays good swallowing function.

PMID- 22953122
TI  - Endoscopic endonasal transturbinate approach to the pterygopalatine fossa in the
      management of juvenile nasopharyngeal angiofibromas.
AB  - Pterygopalatine fossa (PPF) is a difficult-to-access anatomic area located behind
      the posterior wall of the maxillary sinus. Juvenile nasopharyngeal angiofibroma
      (JNA) often affects this area, and the management of feeding artery to the tumor
      is important in the surgery. Endoscopic endonasal approach to the PPF without
      endangering all other nasal structures is useful in the management of JNA. We
      describe a new approach to the PPF, endoscopic transturbinate approach, which is
      effective in the management of JNA. Submucous inferior turbinoplasty was
      performed, and sphenopalatine artery, the feeder to the tumor, was identified at
      the sphenopalatine foramen. The posterior wall of maxillary sinus was removed.
      Internal maxillary artery was identified in the PPF and was ligated with a
      hemoclip. The tumor in the PPF was pushed into the nasal cavity. These procedures
      were all performed via submucous turbinate tunnel. Then, the tumor was
      successfully removed in en bloc from the nasal cavity by transnasal approach
      without ethmoidectomy. This approach improves accessibility and visualization in
      the PPF and potential to reduce intraoperative bleeding due to ligation of the
      feeder safely without touching the tumor. Endoscopic transturbinate approach is
      effective in the management of early stage of JNA.

PMID- 22953123
TI  - Malar bone metastasis revealing a papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma is the most common form of differentiated thyroid
      carcinoma. It is generally confined to the neck with or without spread to
      regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly
      include lung and bone. Metastases involving oral and maxillofacial region are
      extremely rare. We described a case of malar metastasis revealing a follicular
      variant of papillary thyroid carcinoma, presenting with pain and swelling of the
      left cheek in a 67-years-old female patient with an unspecified histological left
      lobo-isthmectomy medical history. To our knowledge, this is the first recorded
      instance of a malar metastasis from a follicular variant of papillary thyroid
      carcinoma.

PMID- 22953124
TI  - Endonasal surgery after cocaine abuse: safe at any interval?
AB  - Objective. We report a case of poor healing after endonasal surgery for nasal
      septal perforation ten years after cocaine abuse was ended. Method. The clinical
      findings are presented. Results. A 35-year-old man presented with a small nasal
      septal perforation caused by cocaine abuse. He had stopped using it ten years
      previously so surgery was considered safe. The perforation was surgically closed
      using an endonasal approach. The perforation, however, recurred, the incision
      healing delayed, and a saddle deformity developed. Conclusion. The effects of
      cocaine abuse seem to persist causing poor healing after nasal surgery.
      Prosthetic treatment should be the primary choice. Caution should be employed
      when considering surgery even in small perforations due to cocaine abuse even
      many years after the abuse was terminated.

PMID- 22953125
TI  - Pleomorphic adenoma of base of tongue: is midline mandibulotomy necessary for
      approaching benign base tongue lesions?
AB  - Objective. To report a rare presentation of pleomorphic adenoma, at base tongue,
      excised surgically by a transoral midline glossotomy technique without
      mandibulotomy. Case Report. Pleomorphic adenoma is a benign tumor of the salivary
      gland found rarely in the base of tongue. Surgery is the definitive treatment for
      this tumor, and different approaches have been mentioned in the literature. In
      our case we surgically excised the tumor by a transoral midline glossotomy
      technique without mandibulotomy where we combined the cosmetic advantage of
      transoral technique and the exposure advantage of a glossotomy technique.
      Discussion. We discuss the different approaches to oropharynx, their advantages
      and disadvantages. Primary transoral approach provides better cosmesis but less
      exposure whereas median labiomandibuloglossotomy approach provides more exposure
      but is cosmetically unacceptable. Conclusion. A transoral midline glossotomy
      approach without mandibulotomy provides wide exposure with acceptable cosmesis.

PMID- 22953126
TI  - Embryonal rhabdomyosarcoma in mastoid and middle ear in a 3-year-old girl: a rare
      case report.
AB  - Introduction. The most common sarcoma of childhood is rhabdomyosarcoma,
      approximately 35% of all paediatric rhabdomyosarcomas occur in the head and neck.
      Case Report. A 3-year-old girl referred to our clinic due to serosanguineous
      purulent discharge from her right ear. After paraclinical and pathologic
      evaluation it was diagnosed as embryonic rhabdomyosarcoma. Conclusions. In all
      children with mastoiditis, especially in young children, rhabdomyosarcoma should
      be considered as a differential diagnosis.

PMID- 22953127
TI  - Chronic maxillary sinusitis associated with an unusual foreign body: a case
      report.
AB  - Foreign bodies in maxillary sinuses are unusual clinical conditions, and they can
      cause chronic sinusitis by mucosal irritation. Most cases of foreign bodies in
      maxillary sinus are related to iatrogenic dental manipulation and only a few
      cases with non-dental origin are reported. Oroantral fistulas secondary to dental
      procedures are the most common way of insertion. Treatment is surgical removal of
      the foreign body either endoscopically or with a combined approach, with Caldwell
      Luc procedure if endoscopic approach is inadequate for visualisation. In this
      case, we present a 24-year-old male patient with unilateral chronic maxillary
      sinusitis due to a wooden toothpick in left maxillary sinus. The patient had a
      history of upper second premolar tooth extraction. CT scan revealed sinus
      opacification with presence of a foreign body in left maxillary sinus extending
      from the floor of the sinus to the orbital base. The foreign body, a wooden
      toothpick, was removed with Caldwell-Luc procedure since it was impossible to
      remove the toothpick endoscopically. There was no obvious oroantral fistula in
      the time of surgery, but the position of the toothpick made us to think that it
      was inserted through a previously healed fistula, willingly or accidentally.

PMID- 22953128
TI  - Multiple symmetric lipomatosis: a review of 3 cases.
AB  - Multiple symmetrical lipomatosis, or Madelung's disease, is a rare disease of
      unknown etiology. It is characterized by the presence of loose adipose tissue
      deposits localized in the cervical region and in the upper body. The
      neoformations grow slowly and their initial consequence is purely esthetic. They
      can, however, lead to compression of the laryngotacheal area and of the
      esophagus. This disease usually affects middle-aged males from the Mediterranean
      area with a history of alcohol abuse. Although most cases have been sporadic, a
      few authors have indicated that the disorder may be hereditary. It is thought
      that this pathology originates from an alteration in lipid metabolism. Since the
      patients were asymptomatic temperance and diet was proposed, surgical removal of
      the lipomatose mass is the treatment of choice in case of complications due to
      fat mass compression on upper aerodigestive tract. The authors present three
      cases of Madelung's disease with different and particular manifestations.

PMID- 22953129
TI  - An Unusual Presentation of Ludwig's Angina Complicated by Cervical Necrotizing
      Fasciitis: A Case Report and Review of the Literature.
AB  - Ludwig's angina can seldom be complicated by necrotizing fasciitis. Due to the
      rapidly progressing nature of this infection and the potential for airway
      compromise and death, it is important to be aware of different ways in which this
      disease process can present in order to recognize and treat it emergently. We
      report here an unusual presentation of a case of Ludwig's angina complicated by
      necrotizing fasciitis in an elderly patient. The clinical features, diagnosis,
      and treatment are discussed in detail as well as a brief literature review on
      craniocervical necrotizing fasciitis.

PMID- 22953130
TI  - Right-sided pyriform sinus fistula: a case report and review of the literature.
AB  - Objectives. Pyriform sinus fistulae arise from disturbances in the development of
      the fetal third and fourth branchial pouches and are predominantly found on the
      left side. We report the rare case of a right-sided pyriform sinus fistula
      presenting as a lateral neck abscess. Study Design. Case report. Methods. A 24
      year-old woman presented with a two-week history of right-sided neck abscess. A
      fluoroscopic sinogram revealed a fistulous tract extending from the abscess to
      the apex of the right pyriform sinus. It was determined that the fistula was
      likely a third or fourth branchial remnant, a rare right-sided finding.
      Chemocauterization of the fistulous tract with 40% trichloroacetic acid was used
      to successfully treat the patient. Results. Approximately 93-97% of branchial
      pouch anomalies are left sided. Treatment options include surgical excision and
      cauterization. Conclusions. Branchial cleft cyst and pyriform sinus fistula must
      be considered in the diagnosis of cervical abscess in either side of the neck.

PMID- 22953131
TI  - A Rapidly Enlarging Squamous Inclusion Cyst in an Axillary Lymph Node following
      Core Needle Biopsy.
AB  - A 73-year-old woman was found to have a 1.7 cm axillary mass, for which a core
      needle biopsy was performed. The specimen revealed fragmented squamous epithelium
      surrounded by lymphoid tissue consistent with a squamous inclusion cyst in a
      lymph node, but a metastatic squamous cell carcinoma could not be excluded.
      Within one month, the lesion enlarged to 5 cm and was excised. Touch preparation
      cytology during intraoperative consultation displayed numerous single and sheets
      of atypical epithelioid cells with enlarged nuclei and occasional mitoses,
      suggesting a carcinoma. However, multinucleated giant cells and neutrophils in
      the background indicated reactive changes. We interpreted the touch preparation
      as atypical and recommended conservative surgical management. Permanent sections
      revealed a ruptured squamous inclusion cyst in a lymph node with extensive
      reactive changes. Retrospectively, the atypical epithelioid cells on touch
      preparation corresponded to reactive histiocytes. This is the first case report
      of a rapidly enlarging ruptured squamous inclusion cyst in an axillary lymph node
      following core needle biopsy. Our case demonstrates the diagnostic challenges
      related to a ruptured squamous inclusion cyst and serves to inform the readers to
      consider this lesion in the differential diagnosis for similar situations.

PMID- 22953132
TI  - Pigmented tumour of the eyelid with unexpected findings.
AB  - A 63-year-old patient presented with a small painless nodular tumour of his left
      lower eyelid which had increased in size over the last few weeks. The tumour was
      excised by wedge resection and submitted for ophthalmopathologic examination.
      Histopathologic examination revealed a cystic lesion of apocrine origin with
      focal proliferations. The proliferative cells appeared pleomorphic and displayed
      marked atypia. Staining with Ki67 revealed a significant mitotic activity
      supporting the diagnosis of an apocrine adenocarcinoma of Moll. As the lesion
      displayed in most parts characteristics of a benign apocrine hidrocystoma, a
      thorough and critical histopathological examination is required in such cases to
      avoid missing an early malignant transformation.

PMID- 22953133
TI  - Perivascular epithelioid cell tumor of the ileum presenting as diverticulitis.
AB  - Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal
      neoplasms. Gastrointestinal PEComas are exceptionally rare, there being only a
      few case reports in the literature involving the colon and small intestine.
      Nearly all PEComas show immunoreactivity for both melanocytic (HMB45 and/or Melan
      A) and smooth muscle (actin and/or desmin) markers. A 36-year-old male was
      admitted to the hospital with acut- abdomen. At laparatomy, a nodular mass
      protruding from the ileum which clinically simulated a diverticulitis was
      noticed. Gross examination of the specimen revealed a 2 * 1,5 * 1 cm secondarily
      ulcerated, solid, nodular, gray white tumor mass in the ileal wall.
      Histologically, tumor cells were composed of nests of round-polygonal epithelioid
      cells with abundant clear to slightly eosinophilic granular cytoplasm and round
      vesicular nuclei. The nests were separated by thin fibrovascular septa. Minimal
      necrosis and low mitotic activity were noticed in the tumor.
      Immunohistochemically, tumor cells were positive for SMA, HMB45, and Melan-A and
      negative for CD10, RCC, CD45, CD117, CD34, EMA, and Desmin. Diagnosis was PEComa
      of the ileum. We report the case of ileal PEComa to remind the unusual
      presentation (diverticulitis) of these tumors, besides rarity and diagnostic
      difficulties.

PMID- 22953134
TI  - Primary leiomyosarcoma of breast in an adolescent girl: a case report and review
      of the literature.
AB  - Leiomyosarcoma of the breast is a rare neoplasm, primarily reported in older
      women. Only 44 cases have been reported in world literature and to the best of
      our knowledge, no case has been reported from India till date. We report a case
      of primary breast leiomyosarcoma in an adolescent girl who underwent a lumpectomy
      for rapidly increasing lump in the left breast. Here we report the histological
      findings and immunohistochemical profile of this entity, along with a review of
      existing literature.

PMID- 22953135
TI  - Uterine Angioleiomyoma with Atypia, Raised CA-125 Levels, and Pseudo-Meigs
      Syndrome: An Alarming Presentation.
AB  - Angioleiomyomas are benign mesenchymal tumours commonly occurring in the subcutis
      of extremities. They are typically composed of interlacing fascicles of smooth
      muscle cells with intersecting vascular channels. Angioleiomyomas of the uterus
      are rare with only very few case reports available in literature. Herein, we
      report a case of this rare entity in a 47-year-old woman owing to its highly
      unusual features of cellular atypia, raised CA-125 levels, and pseudo Meigs
      syndrome.

PMID- 22953136
TI  - Malignant fibrous histiocytoma of the breast: a case report.
AB  - This paper concerns a case of Malignant Fibrous Histiocytoma (MFH) of the Breast
      in a 73-years-old woman. A lump was found in her right breast, measuring 1.7 cm
      in diameter. Surgical excision followed, and pathology revealed a highly atypical
      spindle cell tumor. Immunohistochemistry along the histological features,
      excluded the possibility of carcinoma, malignant phyllodes tumor, or another type
      of pure sarcoma. There was no history of previous irradiation in the region. MFH
      is among the rarest types of sarcoma of the breast, and most of the times behaves
      aggressively. Excision with wide, free-of-tumor margins is the most effective
      treatment, when feasible.

PMID- 22953137
TI  - Laparoscopic resection of a gastric plasma cell granuloma: a case report.
AB  - Plasma cell granuloma, also known as inflammatory myofibroblastic tumour or
      inflammatory pseudotumour, is a nonneoplastic process characterized by an
      unregulated growth of inflammatory cells. It most commonly occurs in the lung and
      upper respiratory tract, and only six other cases of gastric plasma cell
      granuloma exist. There are no other cases of intragastric laparoscopic resection
      of this type of lesion. Here, we present a case of a 60-year-old gentleman who
      had gradual onset epigastric discomfort and was thought to have a
      gastrointestinal stromal tumour on gastroscopy. Subsequent imaging and
      laparoscopic transgastric resection of the lesion confirmed the presence of a
      plasma cell granuloma. We discuss the aetiologies, presentation, investigation,
      and treatment of this rare disorder and make recommendations on the management.

PMID- 22953138
TI  - Multiple-system atrophy in long-term professional painter: a case report.
AB  - Introduction. Multiple system atrophy (MSA) is a rare and severe adult-onset,
      sporadic, and progressive neurodegenerative disorder. Here, we describe an
      autopsy case of MSA in a long-term professional painter. Although typical glial
      cytoplasmic inclusion (GCI) was not observed in a routine histological
      examination, strong alpha-synuclein immunostaining in the nucleus confirmed the
      diagnosis of MSA. Case Presentation. A 48-year-old Japanese man with a long
      occupational history of professional painter was sent to the emergency room,
      where he died of multiple organ failure. The patient had suffered tremors and
      inarticulateness at age 28, developed diabetes at 42 and was diagnosed with
      spinocerebellar degeneration at 46. A histopathological examination showed severe
      neuronal loss, gliosis, and tissue rarefaction in the paleostriatum, striate body
      of the substantia nigra, the pons, and the olivary nucleus of the upper medulla
      oblongata, intermediolateral of the spinal gray matter (sacral region). alpha
      synuclein-positive GCI in oligodendroglia was occurred in the cerebral cortex,
      the midbrain, the medulla oblongata, and the spinal cord. These findings
      confirmed the presence of multiple-system atrophy (OPCA+SDS). Conclusion.
      Although the pathogenesis of MSA is still unclear, prolonged, and extensive
      exposure to organic solvents, together with a hyperglycemic morbidity attributed
      to diabetes, may have contributed to the onset and clinical course of the present
      case.

PMID- 22953139
TI  - Disseminated cryptococcosis in an immunocompetent patient: a case report.
AB  - Cryptococcus neoformans is ubiquitous encapsulated yeast found throughout the
      world. It predominantly causes significant infections in immunocompromised
      individuals, of which 80-90% occur in people with human immunodeficiency virus
      (HIV) infection. Disseminated cryptococcal infection is uncommon and almost
      always occurs in HIV-infected patients. Disseminated disease, especially
      noncutaneous cryptococcal abscess in immunocompetent hosts, is exceedingly rare.
      We report a case of disseminated cryptococcosis with soft tissue, pulmonary, and
      cerebral involvement in an otherwise healthy immunocompetent patient initially
      diagnosed by fine needle aspiration cytology (FNAC).

PMID- 22953140
TI  - Optic nerve hemangioblastoma: a case report.
AB  - Hemangioblastomas are World Health Organization (WHO) grade I tumors of uncertain
      histologic origin. These central nervous system tumors are most often found in
      the posterior fossa, brainstem, and spinal cord. There are fewer than 20 reported
      cases of optic nerve hemangioblastomas in the literature. We present a patient
      with visual decline found to have a mass arising from within the posterior
      orbital canal that grossly involved the optic nerve sheath. Neuropathologic
      evaluation showed hemangioblastoma. Although not a common tumor in this location,
      consideration of hemangioblastoma in the differential diagnosis is important as
      they can have a more aggressive course than other tumors of this region and have
      a detrimental effect on visual prognosis.

PMID- 22953141
TI  - Hereditary neuropathy with liability to pressure palsy presenting with hand drop
      in a young child.
AB  - Hereditary neuropathy with liability to pressure palsy (HNPP) results from the
      deletion of the PMP22 gene in chromosome 17p11.2. Clinically, it presents with
      painless pressure palsies, typically in the 2nd and 3rd decades of life, being a
      rare entity in childhood. We present the case study of a six-year-old male child
      who presented with left hand drop that he kept for over four weeks.
      Electrophysiological studies suggested HNPP and genetic studies confirmed it.
      With this paper, we pretend to create awareness to this entity as a diagnosis to
      be considered in a child with painless monoparesis and to emphasize the
      importance of electrophysiological studies in the diagnosis.

PMID- 22953142
TI  - A case report of idiopathic omental infarction in an obese child.
AB  - Omental infarction (OI) is a rare cause of acute abdomen in children. A 9-year
      old girl was presented with sudden-onset intermittent right lower quadrant
      abdominal pain and fever (37.9 degrees C). Physical examination revealed
      abdominal tenderness in the right lower quadrant with localized rebound
      tenderness which resembled acute appendicitis. She was obese and her BMI was on
      the 99th percentile. Computed tomography (CT) revealed a 5 cm ill-defined
      heterogeneous fatty mass with hyperattenuating streaks just beneath the abdominal
      wall. She was diagnosed as OI and treated conservatively with reduced meals and
      antibiotics. Her symptom resolved gradually and she was discharged on day 7
      without complications. OI should be considered as a differential diagnosis for
      acute right-sided abdominal pain, especially in obese children. Enhanced CT is
      useful for differentiating OI from other conditions presenting with acute
      abdomen.

PMID- 22953143
TI  - Mild form of treacher collins syndrome imitating juvenile otosclerosis.
AB  - Treacher Collins syndrome (TCS) is an inherited developmental disorder. More than
      40% of individuals with TCS have conductive hearing loss attributed to external
      and middle ear anomalies. Mild cases of TCS often pass undiagnosed at birth or
      early childhood. The disease may be manifested as conductive hearing loss in
      teenagers and may resemble juvenile otosclerosis. Patients could suffer from
      slight facial variabilities including retrognathia (as in our case) and others,
      which point out to a possible middle ear anomaly. Surgical corrections of middle
      ear anomalies including TCS generally lead to poorer outcomes comparing with
      juvenile otosclerosis, which should be discussed with parents during preoperative
      counselling.

PMID- 22953144
TI  - Pulmonary alveolar proteinosis in association with congenital dyserythropoietic
      anemia: a case report.
AB  - A two-year-old girl with congenital dyserythropoietic anemia (CDA) acutely
      developed fever, tachypnea, and increased oxygen requirement. Chest X-ray
      revealed bilateral interstitial infiltrates and mild cardiomegaly. Blood cultures
      grew no infectious agents, while pulmonary specimens grew cytomegalovirus (CMV).
      Treatment with intravenous ganciclovir was initiated but without response. Final
      cytologic preparations of bronchoalveolar lavage (BAL) fluid revealed
      eosinophilic amorphous material consistent with pulmonary alveolar proteinosis
      (PAP). CDA and PAP are extremely rare disorders in pediatrics. PAP should be
      considered in patients with hematological disorders who present with acute
      interstitial pneumonia, after infectious causes are ruled out.

PMID- 22953145
TI  - Hair dye poisoning in a paediatric patient.
AB  - Hair dye ingestion with suicidal intention has increased among rural Indian
      population and is associated with significant mortality. We report a teenager who
      presented with cervicofacial edema, respiratory distress, rhabdomyolysis, and
      myocarditis after ingesting the hair dye Super Vasmol 33. Early and supportive
      treatment can prevent morbidity and mortality.

PMID- 22953146
TI  - Neural Changes following Behavioral Activation for a Depressed Breast Cancer
      Patient: A Functional MRI Case Study.
AB  - Functional neuroimaging is an innovative but at this stage underutilized method
      to assess the efficacy of psychotherapy for depression. Functional magnetic
      resonance imaging (fMRI) was used in this case study to examine changes in brain
      activity in a depressed breast cancer patient receiving an 8-session Behavioral
      Activation Treatment for Depression (BATD), based on the work of Hopko and Lejuez
      (2007). A music listening paradigm was used during fMRI brain scans to assess
      reward responsiveness at pre- and posttreatment. Following treatment, the patient
      exhibited attenuated depression and changes in blood oxygenation level dependence
      (BOLD) response in regions of the prefrontal cortex and the subgenual cingulate
      cortex. These preliminary findings outline a novel means to assess psychotherapy
      efficacy and suggest that BATD elicits functional brain changes in areas
      implicated in the pathophysiology of depression. Further research is necessary to
      explore neurobiological mechanisms of change in BATD, particularly the potential
      mediating effects of reward responsiveness and associated brain functioning.

PMID- 22953147
TI  - Lithium toxicity and neurologic effects: probable neuroleptic malignant syndrome
      resulting from lithium toxicity.
AB  - Introduction. We present the case of a patient who developed lithium toxicity
      with normal therapeutic levels, as a result of pharmacokinetic interaction with
      Valsartan, and probable Neuroleptic Malignant Syndrome from the ensuing lithium
      toxicity. Case Presentation. A 59-year old black male with bipolar disorder
      maintained on lithium and fluphenazine therapy presented with a 2 week history of
      worsening confusion, tremor, and gait abnormality. He recently had his dose of
      Valsartan increased. At presentation, patient had signs of autonomic instability,
      he was confused, dehydrated, and had rigidity of upper extremities. Significant
      labs on admission were lithium level-1.2, elevated CK-6008, leukocytosis WBC-22,
      and renal impairment; Creatinine-4.1, BUN-35, HCO(3)-20.1, and blood glucose 145.
      CT/MRI brain showed old cerebral infarcts, and there was no evidence of an
      infective process. Lithium and fluphenazine were discontinued, his lithium levels
      gradually decreased, and he improved with supportive treatment including
      rehydration and correction of electrolyte imbalance. Conclusions. This case
      illustrates that lithium toxicity can occur within therapeutic levels, and the
      neurotoxic effect of lithium can include Neuroleptic Malignant Syndrome.
      Clinicians should be aware of the risk associated with drug interactions with
      lithium.

PMID- 22953148
TI  - Othello syndrome secondary to ropinirole: a case study.
AB  - This case report describes a forty-two-year-old man with no previous psychiatric
      history who developed delusional jealousy (Othello Syndrome) associated with
      ropinirole treatment. Ropinirole is a commonly used dopamine receptor agonist,
      which was being used to treat his Parkinson's disease, and his delusional
      symptoms resolved entirely with ropinirole dose reduction.

PMID- 22953149
TI  - Maintenance electroconvulsive therapy in a patient with treatment-resistant
      paranoid schizophrenia and comorbid epilepsy.
AB  - The treatment of choice for acute schizophrenia is antipsychotic drug treatment
      and electroconvulsive therapy (ECT) and should only be considered as an option
      for treatment-resistant schizophrenia, where treatment with clozapine has already
      proven ineffective or intolerable. The use of ECT as a maintenance treatment for
      patients with schizophrenia and comorbid epilepsy is uncommon as scant evidence
      exists to support this. We describe a patient with a serious case of paranoid
      schizophrenia and comorbid epilepsy who had not responded to typical and atypical
      antipsychotic medication, but responded remarkably to acute ECT and required
      maintenance ECT to sustain a positive therapeutic response.

PMID- 22953150
TI  - Tar Barreler's Hump: An Unusual Presentation of a Posttraumatic Pseudolipoma.
AB  - This is an interesting paper of a 4 cm posttraumatic pseudolipoma on the back of
      the neck of an adult man who has participated in "tar barrel rolling" since
      adolescence. To the best of our knowledge, this is the first case of a
      pseudolipoma to be reported in the literature in association with tar barreling.

PMID- 22953151
TI  - Rheumatoid arthritis and Swine influenza vaccine: a case report.
AB  - Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease.
      Multiple scientific articles have documented that vaccinations for influenza,
      MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed
      individuals. However, there is limited data regarding the association of swine
      flu vaccine (H1N1) and RA. We report the case of a Mexican American female who
      developed RA right after vaccination with H1N1 vaccine. Genetically, RA has
      consistently been associated with an epitope in the third hypervariable region of
      the HLA-DR beta chains, known as the "shared epitope", which is found primarily
      in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with
      susceptibility to RA in Mexican Americans. Hence, certain individuals with the
      presence of the "shared epitope" may develop RA following specific vaccinations.
      To our knowledge, this is the first reported case of RA following vaccination
      with the swine flu vaccine.

PMID- 22953152
TI  - Sarcoidosis presenting as massive splenic infarction.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown aetiology.
      Granulomatous inflammation involving the spleen is common and associated with
      splenomegaly. However, massive splenomegaly is a rare occurrence. Infrequently
      massive splenomegaly can result in splenic infarction. Massive splenic infarction
      in sarcoidosis has, to our knowledge, not been previously reported. We present a
      case of a woman presenting with massive splenic infarction and sarcoidosis
      confirmed by granulomatous inflammation of the liver.

PMID- 22953153
TI  - Abdominal wall hydatid cyst: case report and review of literature.
AB  - A 60-year-old woman presented with a swelling in right paraumbilical region of
      one-year duration. Examination revealed a painless cystic swelling 15 * 10 cm
      with cough impulse. Ultrasound and CECT abdomen showed a subcutaneous cystic
      swelling with intramuscular extension. No other intraabdominal cystic lesions
      were found. Surgical exploration showed a cystic lesion adherent to peritoneum
      without any intraperitoneal extension. Cyst was carefully excised without any
      spillage. Gross specimen on opening showed multiple daughter cysts consistent
      with hydatid cyst, confirming the diagnosis of solitary abdominal wall hydatid
      cyst.

PMID- 22953154
TI  - Plasmacytoid urothelial carcinoma of the bladder metastatic to the stomach: a
      case report.
AB  - Introduction. Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare
      histological variant of urothelial carcinoma that was recently identified.
      Available data on this histological variant is limited. Case Report. We report
      the case of a 75-year-old man with presumed history of high-grade urothelial
      cancer of the bladder, treated with transurethral resection and Bacille Calmette
      Guerin (BCG) in 2004. Six years after treatment of the bladder cancer, the
      patient underwent gastrectomy for an undifferentiated carcinoma of the stomach.
      On followup, patient developed right ureterohydronephrosis and peritoneal
      carcinomatosis. Biopsy of the bladder during stent placement revealed a
      plasmacytoid urothelial carcinoma of the bladder. Rereadings revealed that the
      initial bladder and gastric malignancies were also plasmacytoid carcinoma,
      indicating that, the patient had since 2004, a PUC of the bladder that spread to
      the stomach and peritoneal cavity. Conclusion. Plasmacytoid urothelial carcinoma
      of the bladder is an aggressive variant of urothelial carcinoma. Based on our
      case and the literature review, this tumor can be misdiagnosed because of its
      rarity, leading to treatment delays. Both the urologist and the pathologist need
      to have a high index of suspicion for PUC whenever they encounter unusual
      clinical and/or pathological findings.

PMID- 22953155
TI  - Survival after left ventricular free wall rupture in an elderly woman with acute
      myocardial infarction treated only medically.
AB  - Pseudoaneurysm of the left ventricle is rare and may occur as a result of
      transmural myocardial infarction. The course of rupture after acute myocardial
      infarction varies from a catastrophic event, with an acute tear leading to
      immediate death (acute rupture), or slow and incomplete tear leading to a late
      rupture (subacute rupture). Incomplete rupture may occur when the thrombus and
      haematoma together with the pericardium seal the rupture of the left ventricle
      and may develop into a pseudoaneurysm. Early diagnosis and treatment is essential
      in this condition. Two-dimensional color Doppler echocardiography is the first
      choice method for most patients with suspected left ventricular pseudoaneurysm
      (LVP) and suggests left ventricular rupture in 85% to 90% of patients. We report
      the case of an 87-year-old woman presenting with symptoms and findings of
      myocardial infarction and left ventricular free wall rupture with a
      pseudoaneurysm formation diagnosed by echocardiography and confirmed on CT, MRI,
      and NM. She received only intense medical treatment, because she refused surgery
      with a favorable outcome. After 24-month followup, she is in NYHA functional
      class II. The survival of this patient is due to the contained pseudoaneurysm by
      dense pericardial adhesions, related to her previous coronary bypass surgery.

PMID- 22953156
TI  - How Are n-3 LCPUFAs Antiarrhythmic? A Reassessment of n-3 LCPUFAs in Cardiac
      Disease.
AB  - Long-chain n-3-polyunsaturated fatty acids (n-3 LCPUFAs), referring particularly
      to marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      have been shown to be effective in treating arrhythmias in some clinical trials
      and animal studies. The mechanism for this effect of n-3 LCPUFAs is not well
      understood. Experimental studies and clinical trials published in the 1980s and
      1990s suggested that n-3 LCPUFAs may be antiarrhythmic drugs, but more recent
      trials have not confirmed this. In this paper, we examine evidence for, and
      against, the direct antiarrhythmic action of n-3 LCPUFAs and suggest that
      antistructural remodeling effects of n-3 LCPUFAs may be more relevant in
      accounting for their clinical effects.

PMID- 22953157
TI  - Risk assessment in Finland: theory and practice.
AB  - The Finnish risk assessment practice is based on the Occupational Safety and
      Health (OSH) Act aiming to improve working conditions in order maintain the
      employees' work ability, and to prevent occupational accidents and diseases. In
      practice there are hundreds of risk assessment methods in use. A simple method is
      used in small and medium sized enterprises and more complex risk evaluation
      methods in larger work places. Does the risk management function in the work
      places in Finland? According to our experience something more is needed. That is,
      understanding of common and company related benefits of risk management. The
      wider conclusion is that commitment for risk assessment in Finland is high
      enough. However, in those enterprises where OSH management was at an acceptable
      level or above it, there were also more varied and more successfully accomplished
      actions to remove or reduce the risks than in enterprises, where OSH management
      was in lower level. In risk assessment it is important to process active
      technical prevention and exact communication, increase work place attraction and
      increase job satisfaction and motivation. Investments in OSH are also good
      business. Low absenteeism due to illness or accidents increases directly the
      production results by improved quality and quantity of the product. In general
      Finnish studies have consistently shown that the return of an invested euro is
      three to seven-old. In national level, according to our calculations the savings
      could be even 20% of our gross national product.

PMID- 22953158
TI  - Risk Assessment in the UK Health and Safety System: Theory and Practice.
AB  - In the UK, a person or organisation that creates risk is required to manage and
      control that risk so that it is reduced 'So Far As Is Reasonably Practicable'
      (SFAIRP). How the risk is managed is to be determined by those who create the
      risk. They have a duty to demonstrate that they have taken action to ensure all
      risk is reduced SFAIRP and must have documentary evidence, for example a risk
      assessment or safety case, to prove that they manage the risks their activities
      create. The UK Health and Safety Executive (HSE) does not tell organisations how
      to manage the risks they create but does inspect the quality of risk
      identification and management. This paper gives a brief overview of where
      responsibility for occupational health and safety lies in the UK, and how risk
      should be managed through risk assessment. The focus of the paper is three recent
      major UK incidents, all involving fatalities, and all of which were wholly
      avoidable if risks had been properly assessed and managed. The paper concludes
      with an analysis of the common failings of risk assessments and key actions for
      improvement.

PMID- 22953159
TI  - Occupational health policies on risk assessment in Japan.
AB  - Industrial Safety and Health Law (ISH Law) of Japan requires abnormalities
      identified in evaluations of worker health and working environments are reported
      to occupational physicians, and employers are advised of measures to ensure
      appropriate accommodations in working environments and work procedures. Since the
      1980s, notions of a risk assessment and occupational safety and health management
      system were expected to further prevent industrial accidents. In 2005, ISH Law
      stipulated workplace risk assessment using the wording "employers shall
      endeavor." Following the amendment, multiple documents and guidelines for risk
      assessment for different work procedures were developed. They require ISH Laws to
      be implemented fully and workplaces to plan and execute measures to reduce risks,
      ranking them from those addressing potential hazards to those requiring workers
      to wear protective articles. A governmental survey in 2005 found the performance
      of risk assessment was 20.4% and common reasons for not implementing risk
      assessments were lack of adequate personnel or knowledge. ISH Law specifies
      criminal penalties for both individuals and organizations. Moreover, under the
      Labor Contract Law promulgated in 2007, employers are obliged to make reasonable
      efforts to ensure employee health for foreseeable and avoidable risks. Therefore,
      enterprises neglecting even the non-binding provisions of guidelines are likely
      to suffer significant business impact if judged to be responsible for industrial
      accidents or occupational disease. To promote risk assessment, we must strengthen
      technical, financial, and physical support from public-service organizations,
      encourage the dissemination of good practices to reduce risks, and consider
      additional employer incentives, including relaxed mandatory regulations.

PMID- 22953160
TI  - Advanced korean industrial safety and health policy with risk assessment.
AB  - This article describes a systematic roadmap master plan for advanced industrial
      safety and health policy in Korea, with an emphasis on. Since Korean industries
      had first emergence of industrial safety and health policy in 1953, enormous
      efforts have been made on upgrading the relevant laws in order to reflect real
      situation of industrial work environment in accordance with rapid changes of
      Korean and global business over three decades. Nevertheless, current policy has
      major defects; too much techniques-based articles, diverged contents in less
      organization, combined enforcement and punishments and finally enforcing
      regulations full of commands and control. These deficiencies have make it
      difficult to accommodate changes of social, industrial and employment environment
      in customized fashion. The approach to the solution must be generic at the level
      of paradigm-shift rather than local modifications and enhancement. The basic idea
      is to establish a new system integrated with a risk assessment scheme, which
      encourages employers to apply to their work environment under comprehensive
      responsibility. The risk assessment scheme is designed to enable to inspect
      employers' compliances afterwards. A project comprises four yearly phases based
      on applying zones; initially designating and operating a specified risk zone,
      gradually expanding the special zones during a period of 3 years (2010-2012) and
      the final zone expanded to entire nation. In each phase, the intermediate version
      of the system is updated through a process of precise and unbiased validation in
      terms of its operability, feasibility and sustainability with building relevant
      infrastructures as needed.

PMID- 22953161
TI  - Association between Upper Extremity Musculoskeletal Disorders and Psychosocial
      Factors at Work: A Review on the Job DCS Model's Perspective.
AB  - Over years it has been increasingly concerned with how upper extremity
      musculoskeletal disorders (UEMSDs) are attributed to psychosocial job stressors.
      A review study was conducted to examine associations between UEMSDs and
      psychosocial work factors, and to recommend what to consider for the
      associations. For studies in which the job demand-control-support (DCS) model or
      its variables were specifically employed, published papers were selected and
      reviewed. A number of studies have reported relationships between UEMSDs symptoms
      and psychosocial exposure variables. For example, the findings are: higher
      numbness in the upper extremity was significantly attributed to by less decision
      latitude at work; work demands were significantly associated with neck and
      shoulder symptoms while control over time was associated with neck symptoms; and
      the combination of high psychosocial demands and low decision latitude was a
      significant predictor for shoulder and neck pain in a female working population.
      Sources of bias, such as interaction or study design, were discussed. UEMSDs were
      shown to be associated with psychosocial work factors in various studies where
      the job DCS model was addressed. Nonetheless, this review suggests that further
      studies should be conducted to much more clarify the association between UEMSDs
      and psychosocial factors.

PMID- 22953162
TI  - A case study on engineering failure analysis of link chain.
AB  - OBJECTIVES: The objective of this study was to investigate the effect of chain
      installation condition on stress distribution that could eventually cause
      disastrous failure from sudden deformation and geometric rupture. METHODS:
      Fractographic method used for the failed chain indicates that over-stress was
      considered as the root cause of failure. 3D modeling and finite element analysis
      for the chain, used in a crane hook, were performed with a three-dimensional
      interactive application program, CATIA, commercial finite element analysis and
      computational fluid dynamic software, ANSYS. RESULTS: The results showed that the
      state of stress was changed depending on the initial position of the chain that
      was installed in the hook. Especially, the magnitude of the stress was strongly
      affected by the bending forces, which are 2.5 times greater (under the simulation
      condition currently investigated) than that from the plain tensile load. Also, it
      was noted that the change of load state is strongly related to the failure of
      parts. The chain can hold an ultimate load of about 8 tons with only the tensile
      load acting on it. CONCLUSION: The conclusions of this research clearly showed
      that a reduction of the loss from similar incidents can be achieved when an
      operator properly handles the installation of the chain.

PMID- 22953163
TI  - Characteristics of Occupational Exposure to Benzene during Turnaround in the
      Petrochemical Industries.
AB  - OBJECTIVES: The level of benzene exposure in the petrochemical industry during
      regular operation has been well established, but not in turnaround (TA), where
      high exposure may occur. In this study, the characteristics of occupational
      exposure to benzene during TA in the petrochemical companies were investigated in
      order to determine the best management strategies and improve the working
      environment. This was accomplished by evaluating the exposure level for the
      workers working in environments where benzene was being produced or used as an
      ingredient during the unit process. METHODS: From 2003 to 2008, a total of 705
      workers in three petrochemical companies in Korea were studied. Long- and short
      term (< 1 hr) samples were taken during TAs. TA was classified into three stages:
      shut-down, maintenance and start-up. All works were classified into 12 occupation
      categories. RESULTS: The long-term geometric mean (GM) benzene exposure level was
      0.025 (5.82) ppm (0.005-42.120 ppm) and the short-term exposure concentration
      during TA was 0.020 (17.42) ppm (0.005-61.855 ppm). The proportions of TA samples
      exceeding the time-weighted average, occupational exposure level (TWA-OEL in
      Korea, 1 ppm) and the short-term exposure limit (STEL-OEL, 5 ppm) were 4.1% (20
      samples of 488) and 6.0% (13 samples of 217), respectively. The results for the
      benzene exposure levels and the rates of exceeding the OEL were both
      statistically significant (p < 0.05). Among the 12 job categories of
      petrochemical workers, mechanical engineers, plumbers, welders, fieldman and
      scaffolding workers exhibited long-term samples that exceeded the OEL of benzene,
      and the rate of exceeding the OEL was statistically significant for the first two
      occupations (p < 0.05). CONCLUSION: These findings suggest that the periodic work
      environment must be assessed during non-routine works such as TA.

PMID- 22953164
TI  - Occupational burden of cancer in Korea.
AB  - OBJECTIVES: The extent of the occupational cancer burden has rarely been
      estimated in Korea. The aim of this study is to provide an estimation of the
      population attributable fraction (PAF) of occupational cancer in Korea. METHODS:
      Nine kinds of Group 1 carcinogens addressed by the International Agency for
      Research on Cancer (IARC) and 7 kinds of cancer were selected for the target
      carcinogens and diseases, respectively. The prevalence of carcinogen-exposed
      workers was estimated and correction factors were applied so that the value would
      be representative of the total population. Data on relative risk (RR) were taken
      from IARC reports and were compared with the RRs from the studies on Korean
      workers. The PAF was estimated according to Levin's formula. RESULTS: The
      proportion of the general Korean population exposed to carcinogens was 9.7%. The
      PAF of total cancer was 1.1% for incident cancer cases and 1.7% for cancer
      deaths. The PAFs of lung cancer and leukemia were 7.0% and 4.%, respectively.
      With the RRs reported from Korean studies, the PAF for lung cancer and leukemia
      were 3.7% and 3.4%, respectively. CONCLUSION: The PAF in this study (1.1%) was
      lower than that reported in previous studies (2-4%) from developed countries.
      Considering that only 9 of the 29 kinds of Group 1 carcinogens were included in
      this study, the PAF might be underestimated. However, because the process of
      industrialization in Korea differs from that which occurred in other developed
      countries, 1.1% of the PAF might be appropriate for Korea.

PMID- 22953165
TI  - Serum Levels of Interleukin-8 and Tumor Necrosis Factor-alpha in Coal Workers'
      Pneumoconiosis: One-year Follow-up Study.
AB  - OBJECTIVES: Various cytokines induced by inhalation of coal dust may mediate
      inflammation and lead to tissue damage or fibrosis, such as coal workers'
      pneumoconiosis (CWP). METHODS: To investigate the relevance of serum cytokines in
      CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha
      (TNF-alpha) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP
      subjects) were related to cross sectional findings and 1-year progressive changes
      of the pneumoconiosis. Progressive changes of CWP were evaluated by paired
      comparison of chest radiographs. Analysis by a receiver operating characteristic
      curve assessed the biomarker potential of each cytokine. RESULTS: The mean serum
      IL-8 level was significantly higher in CWP compared to controls and IL-8 levels
      correlated with the degree of CWP. The median serum TNF-alpha level was
      significantly higher in subjects with progressive CWP compared to subjects
      without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF
      alpha (0.72) for CWP identification and progression, respectively, indicated the
      biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF
      alpha were 11.63 pg/mL (sensitivity, 69%; specificity, 64%) and 4.52 pg/mL
      (sensitivity, 67%; specificity, 79%), respectively. CONCLUSION: The results
      suggest that high levels of serum IL-8 are associated with the presence of CWP
      and those of serum TNF-alpha are associated with the progression of CWP.

PMID- 22953166
TI  - A Study of Micronucleus Induction with Methyl Formate and 2-Methylbutane in Bone
      Marrow Cells of Male ICR Mice.
AB  - OBJECTIVES: We investigated the genotoxicity of two chemicals, methyl formate and
      2-methylbutane, using male ICR mice bone marrow cells for the screening of
      micronucleus induction. Although these two chemicals have already been tested
      numerous times, a micronucleus test has not been conducted and the amounts used
      have recently been increased. METHODS: 7 week male ICR mice were tested at
      dosages of 250, 500, and 1,000 mg/kg for methyl formate and 500, 1,000, and 2,000
      mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration
      with the two chemicals, the mice were sacrificed and their bone marrow cells were
      prepared for smearing slides. RESULTS: As a result of counting the micronucleated
      polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes, all
      treated groups expressed no statistically significant increase of MNPCE compared
      to the negative control group. There were no clinical signs related with the oral
      exposure of these two chemicals. CONCLUSION: It was concluded that the two
      chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and
      there was no direct proportion with dosage. These results indicate that the two
      chemicals have no mutagenic potential under each study condition.

PMID- 22953167
TI  - Different Effects of Workers' Trust on Work Stress, Perceived Stress, Stress
      Reaction, and Job Satisfaction between Korean and Japanese Workers.
AB  - OBJECTIVES: This study was conducted to investigate the effect of trust on work
      stress. Trust can be classified into three dimensions; social trust,
      institutional trust, and trust in others. The relationship between work stress
      and trust is regarded as having three components. First, trust has an influence
      on work stressors as an antecedent variable; secondly, trust modifies the effect
      of the various stressors, and finally, trust is one of the stressors. METHODS:
      Data for this study was collected by interviews and self-administered structured
      questionnaires from 376 Korean and 77 Japanese workers in small businesses.
      Subjects were selected by two stage stratified random sampling from the working
      population of manufacturing industries. RESULTS: Three different positions of
      trust are significantly related with the stress causation web. Social trust,
      institutional trust and trust in others significantly influence different work
      stressors in both Korean and Japanese workers. Three different kinds of trust
      influence work stressors among Korean workers, but institutional trust has no
      impact on work stressors among Japanese workers. As a moderating variable for
      perceived stress, distrust in an employer is statistically significant in both
      groups. However, stress symptom prevalence among Korean workers is modified by
      caution, trust in career development, and distrust in co-workers, but that of
      Japanese workers is modified only by distrust in employer. Job satisfaction of
      Korean workers is affected by general trust, utility of relation, institutional
      trust and trust in employer, but among Japanese workers, caution, reputation and
      trust in employer have influence on job satisfaction. CONCLUSION: The effect of
      trust on work stress, perceived stress, stress reaction and job satisfaction are
      different among Korean workers and Japanese workers. Three dimensions of trust
      have three different positions as antecedent, moderating and mediating factors in
      stress causation.

PMID- 22953168
TI  - A study for health hazard evaluation of methylene chloride evaporated from the
      tear gas mixture.
AB  - This study explored the health hazard of those exposed to methylene chloride by
      assessing its atmospheric concentration when a tear gas mixture was aerially
      dispersed. The concentration of methylene chloride ranged from 311.1-980.3 ppm
      (geometric mean, 555.8 ppm), 30 seconds after the dispersion started. However,
      the concentration fell rapidly to below 10 ppm after dispersion was completed.
      The concentration during the dispersion did not surpass the National Institute
      for Occupational Safety and Health 'immediately dangerous to life or health'
      value of 2,300 ppm, but did exceed the American Conference of Governmental
      Industrial Hygienists excursion limit of 250 ppm. Since methylene chloride is
      highly volatile (vapor pressure, 349 mmHg at 20C), the postdispersion atmospheric
      concentration can rise instantaneously. Moreover, the o
      chlorobenzylidenemalononitrile formulation of tear gas (CS gas) is an acute upper
      respiratory tract irritant. Therefore, tear gas mixtures should be handled with
      delicate care.

PMID- 22953169
TI  - Towards elimination of asbestos-related diseases: a theoretical basis for
      international cooperation.
AB  - We develop a theoretical framework for international cooperation that can be used
      for the elimination of asbestos-related diseases (ARDs). The framework is based
      on the similarities in the temporal patterns of asbestos use and occurrence of
      ARDs in diverse countries. The status of each nation can be characterized by
      observing asbestos use and ARD frequency therein using a time window. Countries
      that supply technology for prevention of ARDs can be classified as donors and
      countries that receive these technologies as recipients. We suggest
      identification of three levels of core preventative technologies. Development of
      a common platform to gather and manage core preventative technologies will
      combine the strengths of donor countries and the needs of recipient countries.

PMID- 22953170
TI  - Occupational Injury Prevention Research in NIOSH.
AB  - This paper provided a brief summary of the current strategic goals, activities,
      and impacts of the NIOSH (National Institute for Occupational Safety and Health)
      occupational injury research program. Three primary drivers (injury database,
      stakeholder input, and staff capacity) were used to define NIOSH research focuses
      to maximize relevance and impact of the NIOSH injury-prevention-research program.
      Injury data, strategic goals, program activities, and research impacts were
      presented with a focus on prevention of four leading causes of workplace injury
      and death in the US: motor vehicle incidents, falls, workplace violence, and
      machine and industrial vehicle incidents. This paper showcased selected priority
      goals, activities, and impacts of the NIOSH injury prevention program. The NIOSH
      contribution to the overall decrease in fatalities and injuries is reinforced by
      decreases in specific goal areas. There were also many intermediate outcomes that
      are on a direct path to preventing injuries, such as new safety regulations and
      standards, safer technology and products, and improved worker safety training.
      The outcomes serve as an excellent foundation to stimulate further research and
      worldwide partnership to address global workplace injury problems.

PMID- 22953171
TI  - Shift work and health: current problems and preventive actions.
AB  - The paper gives an overview of the problems to be tackled nowadays by
      occupational health with regards to shift work as well as the main guidelines at
      organizational and medical levels on how to protect workers' health and well
      being. Working time organization is becoming a key factor on account of new
      technologies, market globalization, economic competition, and extension of social
      services to general populations, all of which involve more and more people in
      continuous assistance and control of work processes over the 24 hours in a day.
      The large increase of epidemiological and clinical studies on this issue document
      the severity of this risk factor on human health and well being, at both social
      and psychophysical levels, starting from a disruption of biological circadian
      rhythms and sleep/wake cycle and ending in several psychosomatic troubles and
      disorders, likely also including cancer, and extending to impairment of
      performance efficiency as well as family and social life. Appropriate
      interventions on the organization of shift schedules according to ergonomic
      criteria and careful health surveillance and social support for shift workers are
      important preventive and corrective measures that allow people to keep working
      without significant health impairment.

PMID- 22953172
TI  - Risk Factors of Work-related Upper Extremity Musculoskeletal Disorders in Male
      Shipyard Workers: Structural Equation Model Analysis.
AB  - OBJECTIVES: This study was conducted to develop a model describing the
      interaction between lifestyle, job, and postural factors and parts of the upper
      extremities in shipyard workers. METHODS: A questionnaire survey was given to
      2,140 workers at a shipyard in Ulsan City. The questionnaire consisted of
      questions regarding the subjects' general characteristics, lifestyle, tenure,
      physical burden, job control, posture and musculoskeletal symptoms. The overall
      relationship between variables was analyzed by a structural equation model (SEM).
      RESULTS: The positive rate of upper extremity musculoskeletal symptoms increased
      in employees who worked longer hours, had severe physical burden, and did not
      have any control over their job. Work with a more frequent unstable posture and
      for longer hours was also associated with an increased positive rate of
      musculoskeletal symptoms. Multiple logistic regression analysis showed that
      unstable posture and physical burden were closely related to the positive rate of
      musculoskeletal symptoms after controlling for age, smoking, drinking, exercise,
      tenure, and job control. In SEM analysis, work-related musculoskeletal disease
      was influenced directly and indirectly by physical and job stress factors,
      lifestyle, age, and tenure (p < 0.05). The strongest correlations were found
      between physical factors and work-related musculoskeletal disease. CONCLUSION:
      The model in this study provides a better approximation of the complexity of the
      actual relationship between risk factors and work-related musculoskeletal
      disorders. Among the variables evaluated in this study, physical factors (work
      posture) had the strongest association with musculoskeletal disorders.

PMID- 22953173
TI  - Occupational lung cancer surveillance in South Korea, 2006-2009.
AB  - OBJECTIVES: The lung cancer mortality in Korea has increased remarkably during
      the last 20 years, and has been the first leading cause of cancer-related deaths
      since 2000. The aim of the current study was to examine the time trends of
      occupational lung cancer and carcinogens exposure during the period 2006-2009 in
      South Korea, by assessing the proportion of occupational burden. METHODS: We
      defined occupational lung cancer for surveillance, and developed a reporting
      protocol and reporting website for the surveillance of occupational lung cancer.
      The study patients were chosen from 9 participating university hospitals in the
      following 7 areas: Seoul, Incheon, Wonju, Daejeon, Daegu, Busan, and Gwangju.
      RESULTS: The combined proportion of definite and probable occupational lung
      cancer among all lung cancers investigated in this study was 10.0%, 8.6%, 10.7%,
      and 15.8% in the years 2006 to 2009, respectively, with an average of 11.7% over
      the four-year study period. The main carcinogens were asbestos, crystalline
      silica, radon, polyaromatic hydrocarbons (PAHs), diesel exhaust particles,
      chromium, and nickel. CONCLUSION: We estimated that about 11.7% of the incident
      lung cancer was preventable. This reveals the potential to considerably reduce
      lung cancer by intervention in occupational fields.

PMID- 22953174
TI  - Decision tree of occupational lung cancer using classification and regression
      analysis.
AB  - OBJECTIVES: Determining the work-relatedness of lung cancer developed through
      occupational exposures is very difficult. Aims of the present study are to
      develop a decision tree of occupational lung cancer. METHODS: 153 cases of lung
      cancer surveyed by the Occupational Safety and Health Research Institute (OSHRI)
      from 1992-2007 were included. The target variable was whether the case was
      approved as work-related lung cancer, and independent variables were age, sex,
      pack-years of smoking, histological type, type of industry, latency, working
      period and exposure material in the workplace. The Classification and Regression
      Test (CART) model was used in searching for predictors of occupational lung
      cancer. RESULTS: In the CART model, the best predictor was exposure to known lung
      carcinogens. The second best predictor was 8.6 years or higher latency and the
      third best predictor was smoking history of less than 11.25 pack-years. The CART
      model must be used sparingly in deciding the work-relatedness of lung cancer
      because it is not absolute. CONCLUSION: We found that exposure to lung
      carcinogens, latency and smoking history were predictive factors of approval for
      occupational lung cancer. Further studies for work-relatedness of occupational
      disease are needed.

PMID- 22953175
TI  - Biopsychosocial factors and perceived disability in saleswomen with concurrent
      low back pain.
AB  - OBJECTIVES: To quantify disability level in salespeople with concurrent low back
      pain (LBP) and to determine the relative associations between demographic,
      occupational, psychosocial and clinical factors and back disability. LBP is the
      most common cause of work-related disability in people under 45 years of age and
      the most expensive cause of work-related disability, in terms of workers'
      compensation and medical expenses. Evidence suggests high prevalence of LBP in
      salespeople. METHODS: A cross-sectional survey was conducted in which 184
      saleswomen with a current episode of self-reported LBP working in a large up
      scale department store filled out a battery of 6 self-administered questionnaires
      and received a standardised physical examination. RESULTS: Saleswomen with
      concurrent LBP had low disability levels. Factors significantly associated with
      disability were pain intensity, measured by a visual analogue scale, in the past
      week (p < 0.001), physical and mental health status (p < 0.001, p = 0.003,
      respectively), fear avoidance scores for both work and physical activities (p =
      0.031, p = 0.014, respectively), past history of LBP (p = 0.019), and self
      reported frequency of pushing or pulling objects placed in high positions during
      work (p = 0.047). A significant level (45%) of the variance in disability status
      was explained by these variables. CONCLUSION: In clinical management of LBP
      workers who required prolonged standing, such as salespeople, clinicians should
      look for modifiable risk factors associated with disability. Specific measures
      need to be taken to prevent disability due to LBP among salespeople.

PMID- 22953176
TI  - Gender-related Factors Associated with Upper Extremity Function in Workers.
AB  - OBJECTIVES: This study aimed to find gender distinctions in terms of the
      sociology of the population; to determine work-related factors; to analyze gender
      differences in daily living, work, sports, and art performances; and to identify
      gender-related factors that limited performance of daily living and work
      activities. METHODS: A questionnaire was designed that included disabilities of
      the arm, shoulder, and hand (DASH), accident history, disease history, work
      duration at current workplace, marital status, job satisfaction, job autonomy,
      and physical demands of the job. Out of 1,853 workers surveyed, 1,173
      questionnaires (63.3%; 987 males, 186 females) included responses to DASH
      disability and DASH optional work and were judged acceptable for analysis.
      RESULTS: Upper extremity functional limitation during work and daily living was
      higher for females than males. The limitations for males increased according to
      their household work time, accident history, work duration, job satisfaction,
      physical demand, and job autonomy. Meanwhile, female workers' upper extremity
      discomfort was influenced by their disease history, job satisfaction, and
      physical demands. In addition, the size of the company affected male workers'
      upper extremity function, while marriage and hobbies influenced that of female
      workers. CONCLUSION: This study addressed sociodemographic factors and work
      related factors that affect each gender's upper extremity function during daily
      living and working activities. Each factor had a different influence. Further
      studies are needed to identify the effect that role changes, not being influenced
      by risks at work, have on musculoskeletal disorders.

PMID- 22953177
TI  - A Computer-based Training Intervention for Work Supervisors to Respond to
      Intimate Partner Violence.
AB  - OBJECTIVES: Intimate partner violence (IPV), commonly known as domestic violence
      is a problem throughout the world. An estimated 36% to 75% of employed abused
      woman are monitored, harassed and physically assaulted by their partners or ex
      partners while trying to get to work and while at work. The objective of this
      research is to evaluate the effectiveness of interactive training to increase
      knowledge, change perceptions and develop an intention to address domestic
      violence that spills over into the workplace. METHODS: Community-based
      participatory research approaches were employed to develop and evaluate an
      interactive computer-based training (CBT) intervention, aimed to teach
      supervisors how to create supportive and safe workplaces for victims of IPV.
      RESULTS: The CBT intervention was administered to 53 supervisors. All
      participants reacted positively to the training, and there was a significant
      improvement in knowledge between pre- and post-training test performance (72%
      versus 96% correct), effect size (d) = 3.56. Feedback from focus groups was more
      productive than written feedback solicited from the same participants at the end
      of the training. CONCLUSION: Effective training on the impacts of IPV can improve
      knowledge, achieving a large effect size, and produce changes in perspective
      about domestic violence and motivation to address domestic violence in the
      workplace, based on questionnaire responses.

PMID- 22953178
TI  - Vaporization and Conversion of Ethanolamines used in Metalworking Operations.
AB  - OBJECTIVES: This study examined how ethanolamines (EAs) with the same functional
      alcohol group (HOCH(2)CH(2)), such as mono-EA (MEA), di-EA (DEA), and tri-EA
      (TEA), in water-based metalworking fluids (wbMWFs) are vaporized, condensed, and
      transformed by heat generated during metalworking. METHODS: Two types of
      experimental apparatus were manufactured to achieve these objectives. RESULTS:
      Vaporization tests using a water bath showed that the vaporization rate increased
      markedly from 0.19 mg/m(2).min at 23.5C to 8.04 mg/m(2).min at 60C. Chamber tests
      with a heat bulb revealed that "spiked" MEA was fully recovered, while only
      13.32% of DEA and no TEA were recovered. Interestingly, non-spiked types of EAs
      were detected, indicating that heat could convert EAs with more alcohol groups
      (TEA or DEA) into other EAs with fewer group(s) (DEA or MEA). The EA composition
      in fresh fluid was 4% DEA, 66% TEA, and 30% MEA, and in used fluids (n = 5) was
      12.4% DEA, 68% TEA, and 23% MEA. Conversion from TEA into DEA may therefore
      contribute to the DEA increment. Airborne TEA was not detected in 13 samples
      taken from the central coolant system and near a conveyor belt where no machining
      work was performed. The DEA concentration was 0.45 mg/m(3) in the only two
      samples from those locations. In contrast, airborne MEA was found in all samples
      (n = 53) regardless of the operation type. CONCLUSION: MEAs easily evaporated
      even when MWFs were applied, cleaned, refilled, and when they were in fluid
      storage tanks without any metalworking being performed. The conversion of TEA to
      DEA and MEA was found in the machining operations.

PMID- 22953179
TI  - Microbial exposure assessment in sawmill, livestock feed industry, and metal
      working fluids handling industry.
AB  - OBJECTIVES: The objective of this study is to investigate the distribution
      patterns and exposure concentrations of bioaerosols in industries suspected to
      have high levels of bioaerosol exposure. METHODS: We selected 11 plants including
      3 livestock feed plants (LF industry), 3 metal working fluids handling plants
      (MWFs industry), and 5 sawmills and measured total airborne bacteria, fungi,
      endotoxins, as well as dust. Airborne bacteria and fungi were measured with one
      stage impactor, six stage cascade impactor, and gelatin filters. Endotoxins were
      measured with polycarbonate filters. RESULTS: The geometric means (GM) of the
      airborne concentrations of bacteria, fungi, and endotoxins were 1,864, 2,252
      CFU/m(3), and 31.5 EU/m(3), respectively at the sawmills, followed by the LF
      industry (535, 585 CFU/m(3), and 22.0 EU/m(3)) and MWFs industry (258, 331
      CFU/m(3), and 8.7 EU/m(3)). These concentrations by industry type were
      significantly statistically different (p < 0.01). The ratio of indoor to outdoor
      concentration was 6.2, 1.9, 3.2, and 3.2 for bacteria, fungi, endotoxins, and
      dust in the LF industry, 5.0, 0.9, 2.3, and 12.5 in the MWFs industry, and 3.7,
      4.1, 3.3, and 9.7 in sawmills. The respiratory fractions of bioaerosols were
      differentiated by bioaerosol types and industry types: the respiratory fraction
      of bacteria in the LF industry, MWF industry, and sawmills was 59.4%, 72.0%, and
      57.7%, respectively, and that of fungi was 77.3%, 89.5%, and 83.7% in the same
      order. CONCLUSION: We found that bioaerosol concentration was the highest in
      sawmills, followed by LF industry facilities and MWFs industry facilities. The
      indoor/outdoor ratio of microorganisms was larger than 1 and respiratory fraction
      of microorganisms was more than 50% of the total microorganism concentrations
      which might penetrate respiratory tract easily. All these findings suggest that
      bioaerosol in the surveyed industries should be controlled to prevent worker
      respiratory diseases.

PMID- 22953180
TI  - Acute and Subchronic Inhalation Toxicity of n-Octane in Rats.
AB  - OBJECTIVES: We have investigated the toxic effects of the inhalation of
      subchronic and acute levels of n-octane. METHODS: The rats were exposed to n
      octane of 0, 2.34, 11.68 and 23.36 mg/L (n = 5 rats/group/gender) in an acute
      inhalation test (Organization for Economic Co-operation and Development (OECD) TG
      403), or to 0, 0.93, 2.62 and 7.48 mg/L (n = 10 rats/group/gender) for a
      subchronic inhalation test (OECE TG 413), to establish a national chemical
      management system consistent with the Globally Harmonized Classification System
      (GHS). RESULTS: Acutely-exposed rats became lethargic but recovered following
      discontinuation of inhalation. Other clinical symptoms such as change of body
      weight and autopsy finds were absent. The LC50 for the acute inhalation toxicity
      of n-octane was determined to exceed 23.36 mg/L and the GHS category was 'not
      grouping'. Subchronically-treated rats displayed no significant clinical and
      histopathological differences from untreated controls; also, target organs were
      affected hematologically, biochemically and pathologically. Therefore, the no
      observable adverse effect level was indicated as exceeding 7.48 mg/L and the GHS
      category was 'not grouping' for the specific target organ toxicity upon repeated
      exposure. CONCLUSION: However, n-octane exposure should be controlled to be below
      the American Conference of Industrial Hygienists recommendation (300 ppm) to
      prevent inhalation-related adverse health effects of workers.

PMID- 22953181
TI  - Risk factors for breast cancer, including occupational exposures.
AB  - The knowledge on the etiology of breast cancer has advanced substantially in
      recent years, and several etiological factors are now firmly established.
      However, very few new discoveries have been made in relation to occupational risk
      factors. The International Agency for Research on Cancer has evaluated over 900
      different exposures or agents to-date to determine whether they are carcinogenic
      to humans. These evaluations are published as a series of Monographs
      (www.iarc.fr). For breast cancer the following substances have been classified as
      "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to
      diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen
      hormone replacement therapy and exposure to X-radiation and gamma-radiation (in
      special populations such as atomic bomb survivors, medical patients, and in-utero
      exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although
      the evidence for carcinogenicity in epidemiologic studies, and specifically for
      the human breast, is limited. The classification "probably carcinogenic to
      humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco
      smoking, and shift work involving circadian disruption, including work as a
      flight attendant. If the association between shift work and breast cancer, the
      most common female cancer, is confirmed, shift work could become the leading
      cause of occupational cancer in women.

PMID- 22953182
TI  - Diabetes management and hypoglycemia in safety sensitive jobs.
AB  - The majority of people diagnosed with diabetes mellitus are in the working age
      group in developing countries. The interrelationship of diabetes and work, that
      is, diabetes affecting work and work affecting diabetes, becomes an important
      issue for these people. Therapeutic options for the diabetic worker have been
      developed, and currently include various insulins, insulin sensitizers and
      secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors.
      Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment
      side effects. The risk they pose with respect to cognitive impairment can have
      safety implications. The understanding of the therapeutic options in the
      management of diabetic workers, blood glucose awareness training, and self
      monitoring blood glucose will help to mitigate this risk. Employment decisions
      must also take into account the extent to which the jobs performed by the worker
      are safety sensitive. A risk assessment matrix, based on the extent to which a
      job is considered safety sensitive and based on the severity of the
      hypoglycaemia, may assist in determining one's fitness to work. Support at the
      workplace, such as a provision of healthy food options and arrangements for
      affected workers will be helpful for such workers. Arrangements include
      permission to carry and consume emergency sugar, flexible meal times, self
      monitoring blood glucose when required, storage/disposal facilities for medicine
      such as insulin and needles, time off for medical appointments, and structured
      self-help programs.

PMID- 22953183
TI  - Evaluation of the Genetic Toxicity of Cyclopentane and Ammonium Nitrate - In
      vitro Mammalian Chromosomal Aberration Assay in Chinese Hamster Ovary Cells.
AB  - OBJECTIVES: In this study, the in vitro mammalian chromosomal aberration (CA)
      assay was conducted to gain additional information concerning the hazards
      associated with the use of cyclopentane and ammonium nitrate. While these two
      chemicals had already been tested by many methods, they had not been studied in
      the CA test. METHODS: The assay was performed using the ovarian infantile cell
      (CHO-K1 cell), by the direct method (-S9) and by the metabolic activated method
      (+S9 mix). RESULTS: Using the direct method, the 7 dosages in a 48 hour treatment
      group did not show that the frequency of CA is proportion to the dosage addition.
      The frequency of CA is not proportion to the dosage addition for a 6 hour
      treatment using the metabolic activated method. CONCLUSION: From these findings,
      it was decided that the 2 chemicals do not induce chromosomal aberrations under
      the tested conditions.

PMID- 22953184
TI  - Lymphohematopoietic cancer mortality and morbidity of workers in a
      refinery/petrochemical complex in Korea.
AB  - OBJECTIVES: The purpose of this retrospective cohort study was to investigate the
      relationship between exposure of Korean workers to petrochemicals in the
      refinery/petrochemical industry and lymphohematopoietic cancers. METHODS: The
      cohort consisted of 8,866 male workers who had worked from the 1960s to 2007 at
      one refinery and six petrochemical companies located in a refinery/petrochemical
      complex in Korea that produce benzene or use benzene as a raw material.
      Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs)
      were calculated for 1992-2007 and 1997-2005 based on the death rate and cancer
      incidence rate of the Korean male population according to job title (production,
      maintenance, laboratory, and office workers). RESULTS: The overall mortality and
      most cause-specific mortalities were lower among these workers than those of the
      general Korean population. Increased SMRs were observed for leukemia (4/1.45; SMR
      2.77, 95% CI: 0.75-7.09) and lymphohematopoietic cancers (5/2.51; SMR 2, 95% CI:
      0.65-4.66) in production workers, and increased SIRs were also observed in
      leukemia (3/1.34; SIR 2.24, 95% CI: 0.46-6.54) and lymphohematopoietic cancers
      (5/3.39; SIR 1.47, 95% CI: 0.48-3.44) in production workers, but the results were
      not statistically significant. CONCLUSION: The results showed a potential
      relationship between leukemia and lymphohematopoietic cancers and exposure to
      benzene in refinery/petrochemical complex workers. This study yielded limited
      results due to a short observational period; therefore, a follow-up study must be
      performed to elucidate the relationship between petrochemical exposure and cancer
      rates.

PMID- 22953185
TI  - In vivo Genotoxicity of Silver Nanoparticles after 90-day Silver Nanoparticle
      Inhalation Exposure.
AB  - OBJECTIVES: The antimicrobial activity of silver nanoparticles has resulted in
      their widespread use in many consumer products. Yet, despite their many
      advantages, it is also important to determine whether silver nanoparticles may
      represent a hazard to the environment and human health. METHODS: Thus, to
      evaluate the genotoxic potential of silver nanoparticles, in vivo genotoxicity
      testing (OECD 474, in vivo micronuclei test) was conducted after exposing male
      and female Sprague-Dawley rats to silver nanoparticles by inhalation for 90 days
      according to OECD test guideline 413 (Subchronic Inhalation Toxicity: 90 Day
      Study) with a good laboratory practice system. The rats were exposed to silver
      nanoparticles (18 nm diameter) at concentrations of 0.7 * 10(6) particles/cm(3)
      (low dose), 1.4 * 10(6) particles/cm(3) (middle dose), and 2.9 * 10(6)
      particles/cm(3) (high dose) for 6 hr/day in an inhalation chamber for 90 days.
      The rats were killed 24 hr after the last administration, then the femurs were
      removed and the bone marrow collected and evaluated for micronucleus induction.
      RESULTS: There were no statistically significant differences in the
      micronucleated polychromatic erythrocytes or in the ratio of polychromatic
      erythrocytes among the total erythrocytes after silver nanoparticle exposure when
      compared with the control. CONCLUSION: The present results suggest that exposure
      to silver nanoparticles by inhalation for 90 days does not induce genetic
      toxicity in male and female rat bone marrow in vivo.

PMID- 22953186
TI  - Quantitative exposure assessment of various chemical substances in a wafer
      fabrication industry facility.
AB  - OBJECTIVES: This study was designed to evaluate exposure levels of various
      chemicals used in wafer fabrication product lines in the semiconductor industry
      where work-related leukemia has occurred. METHODS: The research focused on 9
      representative wafer fabrication bays among a total of 25 bays in a semiconductor
      product line. We monitored the chemical substances categorized as human
      carcinogens with respect to leukemia as well as harmful chemicals used in the
      bays and substances with hematologic and reproductive toxicities to evaluate the
      overall health effect for semiconductor industry workers. With respect to
      monitoring, active and passive sampling techniques were introduced. Eight-hour
      long-term and 15-minute short-term sampling was conducted for the area as well as
      on personal samples. RESULTS: The results of the measurements for each substance
      showed that benzene, toluene, xylene, n-butyl acetate, 2-methoxyethanol, 2
      heptanone, ethylene glycol, sulfuric acid, and phosphoric acid were non
      detectable (ND) in all samples. Arsine was either "ND" or it existed only in
      trace form in the bay air. The maximum exposure concentration of fluorides was
      approximately 0.17% of the Korea occupational exposure limits, with hydrofluoric
      acid at about 0.2%, hydrochloric acid 0.06%, nitric acid 0.05%, isopropyl alcohol
      0.4%, and phosphine at about 2%. The maximum exposure concentration of propylene
      glycol monomethyl ether acetate (PGMEA) was 0.0870 ppm, representing only 0.1% or
      less than the American Industrial Hygiene Association recommended standard (100
      ppm). CONCLUSION: Benzene, a known human carcinogen for leukemia, and arsine, a
      hematologic toxin, were not detected in wafer fabrication sites in this study.
      Among reproductive toxic substances, n-butyl acetate was not detected, but
      fluorides and PGMEA existed in small amounts in the air. This investigation was
      focused on the air-borne chemical concentrations only in regular working
      conditions. Unconditional exposures during spills and/or maintenance tasks and by
      product chemicals were not included. Supplementary studies might be required.

PMID- 22953187
TI  - Occupational injury statistics in Korea.
AB  - OBJECTIVES: The occupational accident rate was officially reported to be 0.77 per
      100 workers in 2001 and 0.70 in 2009. The stagnant decrease in accident rate
      raises a question about the effectiveness of prevention activity because there
      have been active prevention efforts in the past 10 years. It is also necessary to
      know the exact status of occupational injuries to direct a prevention strategy.
      METHODS: The author re-analyzed occupational injury statistics to find the reason
      for stagnant decreases in occupational injuries. Compensated occupational
      injuries cases were used to calculate fatal and non-fatal injury rates. Injuries
      from commuting accidents and sports activities were excluded as well as
      occupational diseases. The number of workers was adjusted to that of full time
      equivalent employees. RESULTS: The fatal injury rate excluding injuries
      associated with commuting accidents, sports activities, and occupational diseases
      decreased from 12.59 in 2001 to 8.20 in 2009. In 2007, 67.5% of accidents that
      involved being caught in objects, which are mostly caused by machines and
      equipment, occurred in the manufacturing industry; this type of incident has
      decreased since 2001. The fatal and non-fatal injury rates in the manufacturing
      industry have continuously decreased while the rates in the service industry have
      not changed from 2001 to 2009. Non-fatal injuries might not be reported in many
      cases. The number of insured workers was underestimated as long working hours
      were not adjusted for in the reporting system. CONCLUSION: The occupational fatal
      injury rate has decreased and the non-fatal injury rate might have decreased
      during the last 10 years, although the statistics show stagnancy. The decrease of
      the injury rate was countervailed by various factors. Hence, the current accident
      rate does not reflect the actual situation of accidents in Korea. Korea needs to
      develop an improved system to more accurately calculate occupational fatal and
      non-fatal injury rates.

PMID- 22953188
TI  - Determination of Phthalate Metabolites in Human Serum and Urine as Biomarkers for
      Phthalate Exposure Using Column-Switching LC-MS/MS.
AB  - OBJECTIVES: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl
      phthalate (DEHP) are commonly used as plasticizers and their metabolites are
      especially suspected of reproductive toxicity, little is known about occupational
      exposure to those phthalates. The aim of this study was to assess the utility of
      measuring the metabolite concentrations of DBP and DEHP in serum and urine
      samples as an indicator of occupational exposure to those phthalates. METHODS:
      Phthalate metabolites were analyzed by using column-switching high-performance
      liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: We detected
      phthalate metabolites in serum and urine matrices at approximately 10-fold lower
      than the limit of detection of those metabolites in the same matrix by LC-MS/MS
      without column switching, which was sufficient to evaluate concentrations of
      phthalate metabolites for industrial workers and the general population.
      CONCLUSION: The accuracy and precision of the analytical method indicate that
      urinary metabolite determination can be a more acceptable biomarker for studying
      phthalate exposure and adverse health outcomes.

PMID- 22953189
TI  - Multi-Walled Carbon Nanotube (MWCNT) Dispersion and Aerosolization with Hot Water
      Atomization without Addition of Any Surfactant.
AB  - OBJECTIVES: Carbon nanotubes are an important new class of technological
      materials that have numerous novel and useful properties. Multi-walled carbon
      nanotubes (MWCNTs), which is a nanomaterial, is now in mass production because of
      its excellent mechanical and electrical properties. Although MWCNTs appear to
      have great industrial and medical potential, there is little information
      regarding their toxicological effects on researchers and workers who could be
      exposed to them by inhalation during the handling of MWCNTs. METHODS: The
      generation of an untangled MWCNT aerosol with a consistent concentration without
      using surfactants that was designed to be tested in in vivo inhalation toxicity
      testing was attempted. To do this, MWCNTs were dispersed in deionized water
      without the addition of any surfactant. To facilitate the dispersion of MWCNTs in
      deionized water, the water was heated to 40C, 60C, and 80C depending on the
      sample with ultrasonic sonication. Then the dispersed MWCNTs were atomized to
      generate the MWCNT aerosol. After aerosolization of the MWCNTs, the shapes of the
      NTs were examined by transmission electron microscopy. RESULTS: The aerosolized
      MWCNTs exhibited an untangled shape and the MWCNT generation rate was about 50
      mg/m(3). CONCLUSION: Our method provided sufficient concentration and dispersion
      of MWNCTs to be used for inhalation toxicity testing.

PMID- 22953191
TI  - Personal, Occupational, and Public Health Perspectives on Dealing with the First
      Case of Influenza A (H1N1) in the United Arab Emirates.
AB  - New epidemics of infectious diseases often involve health care workers. In this
      short communication we present a case report of a health care professional who
      became the first case of influenza H1N1 virus to be notified in the United Arab
      Emirates. There are several issues related to workplace considerations and
      general public health, including preventive measures, the need for isolation of
      the patient, dealing with contacts, return to work, and communication with the
      workforce.

PMID- 22953190
TI  - The Magnitude of Mortality from Ischemic Heart Disease Attributed to Occupational
      Factors in Korea - Attributable Fraction Estimation Using Meta-analysis.
AB  - OBJECTIVES: Ischemic heart disease (IHD) is a major cause of death in Korea and
      known to result from several occupational factors. This study attempted to
      estimate the current magnitude of IHD mortality due to occupational factors in
      Korea. METHODS: After selecting occupational risk factors by literature
      investigation, we calculated attributable fractions (AFs) from relative risks and
      exposure data for each factor. Relative risks were estimated using meta-analysis
      based on published research. Exposure data were collected from the 2006 Survey of
      Korean Working Conditions. Finally, we estimated 2006 occupation-related IHD
      mortality. RESULTS: FOR THE FACTORS CONSIDERED, WE ESTIMATED THE FOLLOWING
      RELATIVE RISKS: noise 1.06, environmental tobacco smoke 1.19 (men) and 1.22
      (women), shift work 1.12, and low job control 1.15 (men) and 1.08 (women).
      Combined AFs of those factors in the IHD were estimated at 9.29% (0.3-18.51%) in
      men and 5.78% (-7.05-19.15%) in women. Based on these fractions, Korea's 2006
      death toll from occupational IHD between the age of 15 and 69 was calculated at
      353 in men (total 3,804) and 72 in women (total 1,246). CONCLUSION: We estimated
      occupational IHD mortality of Korea with updated data and more relevant evidence.
      Despite the efforts to obtain reliable estimates, there were many assumptions and
      limitations that must be overcome. Future research based on more precise design
      and reliable evidence is required for more accurate estimates.

PMID- 22953192
TI  - Occupational health management in the lead industry: the korean experience.
AB  - In 1967, the problem of occupational lead exposure came to public attention in
      Korea. Since then, regular progress has been made in lowering workplace lead
      exposures, instituting new workplace controls, and implementing health
      examinations of exposed workers. Past serious lead poisoning episodes made it
      possible to introduce biological monitoring programs on a voluntary basis in high
      lead-exposure facilities in Korea. Industry-specific occupational health services
      for lead workers in Korea during the last 22 years can be categorized into three
      phases. During the first phase (1988-1993), efforts were directed at increasing
      awareness among workers about the hazards of lead exposure, biological monitoring
      of blood zinc protoporphyrin began, and a respiratory protection program was
      introduced. During the second phase (1994-1997), a computerized health management
      system for lead workers was developed, blood-lead measurement was added to
      biologic monitoring, and engineering controls were introduced in the workplace to
      lower air-lead levels to comply with air-lead regulations. Finally, during the
      third phase (1998-present), a new biomarker, bone-lead measurement by X-ray
      fluorescence, was introduced. Bone-lead measurement proved to be useful for
      assessing body burden and to demonstrate past lead exposure in retired workers.
      Occupational health service practice for lead workers, including the industry
      specific group occupational health system, has brought considerable success in
      the prevention of lead poisoning and in reducing the lead burden in Korean lead
      workers during the last several decades. The successful achievement of prevention
      of lead poisoning in Korea was a result of the combined efforts of lead workers,
      employers, relevant government agencies, and academic institutes.

PMID- 22953193
TI  - Clinical outcomes of occupational exposure to n,n-dimethylformamide: perspectives
      from experimental toxicology.
AB  - N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the
      production of synthetic leather and resins because of its low volatility, making
      it an attractive industrial material. Despite its excellent property as a
      chemical solvent, utilization of DMF is somewhat controversial nowadays due to
      its hazardous effects on exposed workers in work places. Many toxification cases
      are being reported globally and the number of cases of liver damage is still
      increasing in developing countries. On account of this, a series of epidemiologic
      surveys are being conducted to understand the degrees of liver damage caused by
      DMF exposure. Furthermore, many investigations have been performed to clarify the
      mechanism of DMF-induced liver toxicity using both human and experimental animal
      models. This review summarizes the current occupational cases reported on liver
      damage from workers exposed to DMF in industrial work places and the research
      results that account for DMF-induced liver failure and possible carcinogenesis.
      The findings reviewed here show the synergistic toxicity of DMF exposure with
      other toxicants, which might occur through complicated but distinct mechanisms,
      which may extend our knowledge for establishing risk assessments of DMF exposure
      in industrial work places.

PMID- 22953194
TI  - Review of qualitative approaches for the construction industry: designing a risk
      management toolbox.
AB  - OBJECTIVES: This paper presents the framework and protocol design for a
      construction industry risk management toolbox. The construction industry needs a
      comprehensive, systematic approach to assess and control occupational risks.
      These risks span several professional health and safety disciplines, emphasized
      by multiple international occupational research agenda projects including: falls,
      electrocution, noise, silica, welding fumes, and musculoskeletal disorders. Yet,
      the International Social Security Association says, "whereas progress has been
      made in safety and health, the construction industry is still a high risk
      sector." METHODS: Small- and medium-sized enterprises (SMEs) employ about 80% of
      the world's construction workers. In recent years a strategy for qualitative
      occupational risk management, known as Control Banding (CB) has gained
      international attention as a simplified approach for reducing work-related risks.
      CB groups hazards into stratified risk 'bands', identifying commensurate controls
      to reduce the level of risk and promote worker health and safety. We review these
      qualitative solutions-based approaches and identify strengths and weaknesses
      toward designing a simplified CB 'toolbox' approach for use by SMEs in
      construction trades. RESULTS: This toolbox design proposal includes international
      input on multidisciplinary approaches for performing a qualitative risk
      assessment determining a risk 'band' for a given project. Risk bands are used to
      identify the appropriate level of training to oversee construction work, leading
      to commensurate and appropriate control methods to perform the work safely.
      CONCLUSION: The Construction Toolbox presents a review-generated format to
      harness multiple solutions-based national programs and publications for
      controlling construction-related risks with simplified approaches across the
      occupational safety, health and hygiene professions.

PMID- 22953195
TI  - Cases series of malignant lymphohematopoietic disorder in korean semiconductor
      industry.
AB  - OBJECTIVES: Seven cases of malignant lymphohematopoietic (LHP) disorder were
      claimed to have developed from occupational exposure at two plants of a
      semiconductor company from 2007 to 2010. This study evaluated the possibility of
      exposure to carcinogenic agents for the cases. METHODS: Clinical courses were
      reviewed with assessing possible exposure to carcinogenic agents related to LHP
      cancers. Chemicals used at six major semiconductor companies in Korea were
      reviewed. Airborne monitoring for chemicals, including benzene, was conducted and
      the ionizing radiation dose was measured from 2008 to 2010. RESULTS: The latency
      of seven cases (five leukemiae, a Non-Hodgkin's lymphoma, and an aplastic anemia)
      ranged from 16 months to 15 years and 5 months. Most chemical measurements were
      at levels of less than 10% of the Korean Occupational Exposure Limit value. No
      carcinogens related to LHP cancers were used or detected. Complete-shielded
      radiation-generating devices were used, but the ionizing radiation doses were
      0.20-0.22 uSv/hr (background level: 0.21 uSv/hr). Airborne benzene was detected
      at 0.31 ppb when the detection limit was lowered as low as possible. Ethylene
      oxide and formaldehyde were not found in the cases' processes, while these two
      were determined to be among the 263 chemicals in the list that was used at the
      six semiconductor companies at levels lower than 0.1%. Exposures occurring before
      2002 could not be assessed because of the lack of information. CONCLUSION:
      Considering the possibility of exposure to carcinogenic agents, we could not find
      any convincing evidence for occupational exposure in all investigated cases.
      However, further study is needed because the semiconductor industry is a newly
      developing one.

PMID- 22953196
TI  - Cancer mortality and incidence in korean semiconductor workers.
AB  - OBJECTIVES: The purpose of this study was to evaluate cancer risks in the Korean
      semiconductor industry. METHODS: A retrospective cohort study was performed in
      eight semiconductor factories between 1998 and 2008. The number of subjects was
      113,443 for mortality and 108,443 for incidence. Standardized mortality ratios
      (SMR) and standardized incidence ratios (SIR) were calculated. RESULTS: The SMR
      of leukemia was 0.39 (95% Confidence Interval 0.08-1.14) in males (2 cases) and
      1.37 (0.55-2.81) in females (7 cases). The SMR of non-Hodgkin's lymphoma (NHL)
      was 1.33 (0.43-3.09, 5 cases) in males and 2.5 (0.68-6.40, 4 cases) in females.
      The SIR of leukemia was 0.69 (0.30-1.37, 8 cases) in males and 1.28 (0.61-2.36,
      10 cases) in females. The SIR of NHL in females was 2.31 (1.23-3.95, 13 cases)
      and that of thyroid cancer in males was 2.11 (1.49-2.89, 38 cases). The excess
      incidence of NHL was significant in female assembly operators [SIR=3.15 (1.02
      7.36, 5 cases)], but not significant in fabrication workers. The SIR of NHL in
      the group working for 1-5 years was higher than the SIR of NHL for those working
      for more than five years. The excess incidence of male thyroid cancer was
      observed in both office and manufacturing workers. CONCLUSION: There was no
      significant increase of leukemia in the Korean semiconductor industry. However,
      the incidence of NHL in females and thyroid cancer in males were significantly
      increased even though there was no definite association between work and those
      diseases in subgroup analysis according to work duration. This result should be
      interpreted cautiously, because the majority of the cohort was young and the
      number of cases was small.

PMID- 22953197
TI  - Workers' compensation insurance and occupational injuries.
AB  - OBJECTIVES: Although compensation for occupational injuries and diseases is
      guaranteed in almost all nations, countries vary greatly with respect to how they
      organize workers' compensation systems. In this paper, we focus on three aspects
      of workers' compensation insurance in Organization for Economic Cooperation and
      Development (OECD) countries - types of systems, employers' funding mechanisms,
      and coverage for injured workers - and their impacts on the actual frequencies of
      occupational injuries and diseases. METHODS: We estimated a panel data fixed
      effect model with cross-country OECD and International Labor Organization data.
      We controlled for country fixed effects, relevant aggregate variables, and dummy
      variables representing the occupational accidents data source. RESULTS: First,
      the use of a private insurance system is found to lower the occupational
      accidents. Second, the use of risk-based pricing for the payment of employer
      raises the occupational injuries and diseases. Finally, the wider the coverage of
      injured workers is, the less frequent the workplace accidents are. CONCLUSION:
      Private insurance system, fixed flat rate employers' funding mechanism, and
      higher coverage of compensation scheme are significantly and positively
      correlated with lower level of occupational accidents compared with the public
      insurance system, risk-based funding system, and lower coverage of compensation
      scheme.

PMID- 22953198
TI  - The Effects of Injury and Accidents on Self-rated Depression in Male Municipal
      Firefighters.
AB  - OBJECTIVES: The present study aims to determine the causal relationship between
      self-rated depression and experiences of injury and accidents in municipal
      firefighters. METHODS: A panel survey of 186 municipal firefighters measured with
      depressive symptoms according to the Beck's depression index (BDI) was conducted.
      The effects of job-related injuries and accidents were evaluated using self
      administered questionnaires that were taken once in a 12-month period from 2005
      to 2006. Firefighters were classified into the Depression Group or Control Group
      based on follow-up BDI results with a cutoff level that was set to having "over
      mild depression." RESULTS: The depression Group was comprised of 17 (9.1%)
      workers, including 9 firefighters who met had sufficient BDI scores twice in the
      2-year test period and newly sufficient BDI scores in the follow-up test. A
      significantly higher number of subjects in the Depression Group experienced
      injuries and accidents in the 2-year test period as compared to the Control Group
      (15.4% vs. 1.5%, p=0.04). Firefighters who experienced injuries and accidents in
      the 2-year test period had a 7.4 times higher risk of being in the Depression
      Group than those who had not. As compared to accidents, near-miss accidents
      revealed stronger risks related to being classified as in the Depression group
      (adjusted odds ratio [OR] = 4.58, 95% confidence interval [CI] = 1.15-18.18 vs.
      Adjusted OR = 4.22, 95% CI = 1.08-16.58). CONCLUSION: The above results suggest
      that we should establish an effective program to promote mental health for groups
      at high risk for self-rated depression, including persons who have experienced
      consecutive injuries and accidents as well as near-miss injuries.

PMID- 22953199
TI  - Correlation of Occupational Stress Index with 24-hour Urine Cortisol and Serum
      DHEA Sulfate among City Bus Drivers: A Cross-sectional Study.
AB  - OBJECTIVES: The questionnaire of occupational stress index (OSI) has been popular
      in the workplace, and it has been tailored for bus drivers in Taiwan.
      Nevertheless, its outcomes for participants are based on self-evaluations, thus
      validation by their physiological stress biomarker is warranted and this is the
      main goal of this study. METHODS: A cross-sectional study of sixty-three city bus
      drivers and fifty-four supporting staffs for comparison was conducted.
      Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for
      dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured
      concentrations of these biological measures were logarithmically transformed
      before the statistical analysis where various scores of stressor factors,
      moderators, and stress effects of each OSI domain were analyzed by applying
      multiple linear regression models. RESULTS: For drivers, the elevated 24-hour
      urine cortisol level was associated with a worker's relationship with their
      supervisor and any life change events in the most recent 3 months. The DHEA-S
      level was higher in drivers of younger age as well as drivers with more concerns
      relating to their salary and bonuses. Non-drivers showed no association between
      any stressor or satisfaction and urine cortisol and blood DHEA-S levels.
      CONCLUSION: Measurements of biomarkers may offer additional stress evaluations
      with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may
      result from stressors like income security. Prevention efforts towards
      occupational stress and life events and health promotional efforts for aged
      driver were important anti-stress remedies.

PMID- 22953200
TI  - Occurrence of cognitive and neurological symptoms in norwegian dentists.
AB  - OBJECTIVES: Previous investigations have presented some evidence of late
      cognitive effects in dental personnel exposed to metallic mercury. We wanted to
      examine if Norwegian dentists have an increased prevalence of symptoms consistent
      with neurological and/or cognitive malfunction. METHODS: The study group
      consisted of 406 dentists from central Norway and 217 controls from the general
      population, all under the age of 70. They had responded to a standardised postal
      questionnaire (Euroquest) inquiring about seven symptoms in regard to neurology,
      psychosomatics, memory, concentration, mood, sleep disturbances, and fatigue. A
      score was calculated for each symptom based on 4 to 15 single questions scored on
      a scale from 1 (seldom or never) to 4 (very often). RESULTS: The dentists and
      controls had a participation rate of 57.2% and 42.9% respectively. The dentists
      reported no more cognitive symptoms than the controls, with low average symptom
      scores from 1.16 for neurological symptoms in males to 1.73 for fatigue in
      females. Corresponding figures for the controls were 1.22 and 1.77. There were a
      total of 1.2% of the dentists and 1.8% of the controls who reported having three
      or more of the seven symptoms "often" or more frequently. CONCLUSION: Norwegian
      dentists do not report more cognitive and neurological symptoms than controls
      from the general population.

PMID- 22953201
TI  - Psychosocial Factors and Work-related Musculoskeletal Disorders among
      Southeastern Asian Female Workers Living in Korea.
AB  - OBJECTIVES: A rapid increase in the population of migrant workers in Korea has
      brought new challenges regarding the possible effects of acculturation on health.
      The purpose of this study was to examine the influence of acculturation- and work
      related psychosocial factors on work-related musculoskeletal disorders among
      migrant female workers living in Korea. METHODS: A cross-sectional survey design
      was used. A translated, structured questionnaire was administrated to 156
      southeastern Asian female full-time workers living in Korea. RESULTS: About 35%
      of the participants experienced some type(s) of work-related musculoskeletal
      disorder(s), which were more prevalent in Vietnamese women than in Thai and
      Filipino women. Women who preferred to maintain their own heritage and to reject
      the host country heritage were at risk for work-related musculoskeletal
      disorders. CONCLUSION: Acculturation strategy and nationality were found to be
      significant factors associated with work-related musculoskeletal disorders.
      Health professionals need to accommodate acculturation contexts into risk
      assessment and intervention development for work-related musculoskeletal
      disorders separately for different nationalities.

PMID- 22953202
TI  - Job characteristics in nursing and cognitive failure at work.
AB  - OBJECTIVES: Stressors in nursing put high demands on cognitive control and,
      therefore, may increase the risk of cognitive failures that put patients at risk.
      Task-related stressors were expected to be positively associated with cognitive
      failure at work and job control was expected to be negatively associated with
      cognitive failure at work. METHODS: Ninety-six registered nurses from 11 Swiss
      hospitals were investigated (89 women, 7 men, mean age = 36 years, standard
      deviation = 12 years, 80% supervisors, response rate 48%). A new German version
      of the Workplace Cognitive Failure Scale (WCFS) was employed to assess failure in
      memory function, failure in attention regulation, and failure in action exertion.
      In linear regression analyses, WCFS was related to work characteristics,
      neuroticism, and conscientiousness. RESULTS: The German WCFS was valid and
      reliable. The factorial structure of the original WCF could be replicated.
      Multilevel regression task-related stressors and conscientiousness were
      significantly related to attention control and action exertion. CONCLUSION: The
      study sheds light on the association between job characteristics and work-related
      cognitive failure. These associations were unique, i.e. associations were shown
      even when individual differences in conscientiousness and neuroticism were
      controlled for. A job redesign in nursing should address task stressors.

PMID- 22953203
TI  - Preventive measures to eliminate asbestos-related diseases in singapore.
AB  - The incidence of asbestos-related diseases (ARD) has increased in the last four
      decades. In view of the historical use of asbestos in Singapore since the country
      started banning it in phases in 1989 and the long latency of the disease, the
      incidence of ARD can be expected to increase further. As occupational exposure to
      asbestos still occurs, preventive measures to eliminate ARD continue to be
      required to protect the health of both workers and the public from asbestos
      exposure. The majority of occupational exposures to asbestos at present occur
      during the removal of old buildings. Preventive measures have been utilized by
      different government ministries and agencies in eliminating ARD in Singapore over
      the past 40 years. These measures have included the enforcement of legislation,
      substitution with safer materials, and engineering controls during asbestos
      removal as well as improvements in personal hygiene and the use of personal
      protective equipment. The existing Workman's Compensation System for ARD should
      be further refined, given that is currently stipulates that claims for asbestosis
      and malignant mesothelioma be made within 36 and 12 months after ceasing
      employment.

PMID- 22953204
TI  - Exposure to Volatile Organic Compounds and Possibility of Exposure to By-product
      Volatile Organic Compounds in Photolithography Processes in Semiconductor
      Manufacturing Factories.
AB  - OBJECTIVES: The purpose of this study was to measure the concentration of
      volatile organic compound (VOC)s originated from the chemicals used and/or
      derived from the original parental chemicals in the photolithography processes of
      semiconductor manufacturing factories. METHODS: A total of four photolithography
      processes in 4 Fabs at three different semiconductor manufacturing factories in
      Korea were selected for this study. This study investigated the types of
      chemicals used and generated during the photolithography process of each Fab, and
      the concentration levels of VOCs for each Fab. RESULTS: A variety of organic
      compounds such as ketone, alcohol, and acetate compounds as well as aromatic
      compounds were used as solvents and developing agents in the processes. Also, the
      generation of by-products, such as toluene and phenol, was identified through a
      thermal decomposition experiment performed on a photoresist. The VOC
      concentration levels in the processes were lower than 5% of the threshold limit
      value (TLV)s. However, the air contaminated with chemical substances generated
      during the processes was re-circulated through the ventilation system, thereby
      affecting the airborne VOC concentrations in the photolithography processes.
      CONCLUSION: Tens of organic compounds were being used in the photolithography
      processes, though the types of chemical used varied with the factory. Also, by
      products, such as aromatic compounds, could be generated during photoresist
      patterning by exposure to light. Although the airborne VOC concentrations
      resulting from the processes were lower than 5% of the TLVs, employees still
      could be exposed directly or indirectly to various types of VOCs.

PMID- 22953205
TI  - Feasibility and acceptability of workers' health surveillance for fire fighters.
AB  - OBJECTIVES: The objective of this study was to test the feasibility and
      acceptability of a new workers' health surveillance (WHS) for fire fighters in a
      Dutch pilot-implementation project. METHODS: In three fire departments, between
      November 2007 and February 2009, feasibility was tested with respect to i) worker
      intent to change health and behavior; ii) the quality of instructions for testing
      teams; iii) the planned procedure in the field; and iv) future WHS organisation.
      Acceptability involved i) satisfaction with WHS and ii) verification of the job
      specificity of the content of two physical tests of WHS. Fire fighters were
      surveyed after completing WHS, three testing teams were interviewed, and the
      content of the two tests was studied by experts. RESULTS:  FEASIBILITY: nearly
      all of the 275 fire fighters intended to improve their health when recommended by
      the occupational physician. The testing teams found the instructions to be clear,
      and they were mostly positive about the organisation of WHS. Acceptability: the
      fire fighters rated WHS at eight points (out of a maximum of ten). The experts
      also reached a consensus about the optimal job-specific content of the future
      functional physical tests. CONCLUSION: Overall, it is feasible and acceptable to
      implement WHS in a definitive form in the Dutch fire-fighting sector.

PMID- 22953206
TI  - External quality assessment scheme for biological monitoring of occupational
      exposure to toxic chemicals.
AB  - OBJECTIVES: In this study, we summarized the External Quality Assessment Scheme
      (EQAS) for the biological monitoring of occupational exposure to toxic chemicals
      which started in 1995 and continued until a 31(st) round robin in the spring of
      2010. The program was performed twice per year until 2009, and this was changed
      to once a year since 2010. The objective of the program is to ensure the
      reliability of the data related to biological monitoring from analytical
      laboratories. METHODS: One hundred and eighteen laboratories participated in the
      31(st) round robin. The program offers 5 items for inorganic analysis: lead in
      blood, cadmium in blood, manganese in blood, cadmium in urine, and mercury in
      urine. It also offers 10 items for organic analysis, including hippuric acid,
      methylhippuric acid, mandelic acid, phenylglyoxylic acid, N-methylformamide, N
      methylacetamide, trichloroacetic acid, total trichloro-compounds, trans,trans
      muconic acid, and 2,5-hexanedione in urine. Target values were determined by
      statistical analysis using consensus values. All the data, such as chromatograms
      and calibration curves, were reviewed by the committee. RESULTS: The proficiency
      rate was below 70% prior to the first round robin and improved to over 90% for
      common items, such as PbB and HA, while those for other items still remained in
      the range of 60-90% and need to be improved up to 90%. CONCLUSION: The EQAS has
      taken a primary role in improving the reliability of analytical data. A total
      quality assurance scheme is suggested, including the validation of technical
      documentation for the whole analytical procedure.

PMID- 22953207
TI  - Prediction of peak back compressive forces as a function of lifting speed and
      compressive forces at lift origin and destination - a pilot study.
AB  - OBJECTIVES: To determine the feasibility of predicting static and dynamic peak
      back-compressive forces based on (1) static back compressive force values at the
      lift origin and destination and (2) lifting speed. METHODS: Ten male subjects
      performed symmetric mid-sagittal floor-to-shoulder, floor-to-waist, and waist-to
      shoulder lifts at three different speeds (slow, medium, and fast), and with two
      different loads (light and heavy). Two-dimensional kinematics and kinetics were
      captured. Linear regression analyses were used to develop prediction equations,
      the amount of predictability, and significance for static and dynamic peak back
      compressive forces based on a static origin and destination average (SODA) back
      compressive force. RESULTS: Static and dynamic peak back-compressive forces were
      highly predicted by the SODA, with R(2) values ranging from 0.830 to 0.947.
      Slopes were significantly different between slow and fast lifting speeds (p <
      0.05) for the dynamic peak prediction equations. The slope of the regression line
      for static prediction was significantly greater than one with a significant
      positive intercept value. CONCLUSION: SODA under-predict both static and dynamic
      peak back-compressive force values. Peak values are highly predictable and could
      be readily determined using back-compressive force assessments at the origin and
      destination of a lifting task. This could be valuable for enhancing job design
      and analysis in the workplace and for large-scale studies where a full analysis
      of each lifting task is not feasible.

PMID- 22953208
TI  - Cancer mortality and incidence in cement industry workers in Korea.
AB  - OBJECTIVES: Cement contains hexavalent chromium, which is a human carcinogen.
      However, its effect on cancer seems inconclusive in epidemiologic studies. The
      aim of this retrospective cohort study was to elucidate the association between
      dust exposure in the cement industry and cancer occurrence. METHODS: The cohorts
      consisted of male workers in 6 Portland cement factories in Korea. Study subjects
      were classified into five groups by job: quarry, production, maintenance,
      laboratory, and office work. Cancer mortality and incidence in workers were
      observed from 1992 to 2007 and 1997-2005, respectively. Standardized mortality
      ratios and standardized incidence ratios were calculated according to the five
      job classifications. RESULTS: There was an increased standardized incidence ratio
      for stomach cancer of 1.56 (27/17.36, 95% confidence interval: 1.02-2.26) in
      production workers. The standardized mortality ratio for lung cancer increased in
      production workers. However, was not statistically significant. CONCLUSION: Our
      result suggests a potential association between cement exposure and stomach
      cancer. Hexavalent chromium contained in cement might be a causative carcinogen.

PMID- 22953209
TI  - Employers' Perceptions of Intimate Partner Violence among a Diverse Workforce.
AB  - OBJECTIVES: Intimate partner violence (IPV) is a significant global public health
      concern, affecting 5.3 million US individuals annually. An estimated 1 in 3 women
      globally are abused by an intimate partner in their lifetime, and the effects
      carry over into the workplace. This article examines employers' perceptions of
      IPV in the workplace, targeting supervisors of Latina employees. METHODS:
      Fourteen employers and supervisors of small service-sector companies in Oregon
      were interviewed using semi-structured interviews. Interpretive description was
      used to identify themes. These qualitative interviews preceded and helped to
      formulate a larger workplace intervention study. RESULTS: THE FOLLOWING THEMES
      WERE FOUND AND ARE DETAILED: (1) factors associated with recognizing IPV in the
      workplace, (2) effects of IPV on the work environment and (3) supervisors'
      responses to IPV-active vs. passive involvement. Also, supervisors' suggestions
      for addressing IPV in the workplace are summarized. CONCLUSION: These findings
      demonstrate the need for more IPV-related resources in the workplace to be
      available to supervisors as well as survivors and their coworkers. The needs of
      supervisors and workplaces vary by site, demonstrating the need for tailored
      interventions, and culturally appropriate workplace interventions are needed for
      Latinas and other racially and ethnically diverse populations.

PMID- 22953210
TI  - Risk Assessment of Physical Hazards in Greek Hospitals Combining Staff's
      Perception, Experts' Evaluation and Objective Measurements.
AB  - OBJECTIVES: The promotion of health and safety (H&S) awareness among hospital
      staff can be applied through various methods. The aim of this study was to assess
      the risk level of physical hazards in the hospital sector by combining workers'
      perception, experts' evaluation and objective measurements. METHODS: A cross
      sectional study was designed using multiple triangulation. Hospital staff (n =
      447) filled in an H&S questionnaire in a general hospital in Athens and an
      oncology one in Thessaloniki. Experts observed and filled in a checklist on H&S
      in the various departments of the two hospitals. Lighting, noise and microclimate
      measurements were performed. RESULTS: The staff's perception of risk was higher
      than that of the experts in many cases. The measured risk levels were low to
      medium. In cases of high-risk noise and lighting, staff and experts agreed.
      Staff's perception of risk was influenced by hospital's department, hospital's
      service, years of working experience and level of education. Therefore, these
      factors should be taken into account in future studies aimed at increasing the
      participation of hospital workers. CONCLUSION: This study confirmed the
      usefulness of staff participation in the risk assessment process, despite the
      tendency for staff to overestimate the risk level of physical hazards. The
      combination of combining staff perception, experts' evaluation and objective
      measures in the risk assessment process increases the efficiency of risk
      management in the hospital environment and the enforcement of relevant
      legislation.

PMID- 22953211
TI  - Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories
      Potentially Exposed throughout the Hospital Medication System.
AB  - OBJECTIVES: Studies examining healthcare workers' exposure to antineoplastic
      drugs have focused on the drug preparation or drug administration areas. However,
      such an approach has probably underestimated the overall exposure risk as the
      drugs need to be delivered to the facility, transported internally and then
      disposed. The objective of this study is to determine whether drug contamination
      occurs throughout a facility and, simultaneously, to identify those job
      categories that are potentially exposed. METHODS: This was a multi-site study
      based in Vancouver, British Columbia. Interviews were conducted to determine the
      departments where the drugs travel. Subsequent site observations were performed
      to ascertain those surfaces which frequently came into contact with
      antineoplastic drugs and to determine the job categories which are likely to
      contact these surfaces. Wipe samples were collected to quantify surface
      contamination. RESULTS: Surface contamination was found in all six stages of the
      hospital medication system. Job categories consistently found to be at risk of
      exposure were nurses, pharmacists, pharmacy technicians, and pharmacy receivers.
      Up to 11 job categories per site may be at risk of exposure at some point during
      the hospital medication system. CONCLUSION: We found drug contamination on select
      surfaces at every stage of the medication system, which indicates the existence
      of an exposure potential throughout the facility. Our results suggest that a
      broader range of workers are potentially exposed than has been previously
      examined. These results will allow us to develop a more inclusive exposure
      assessment encompassing all healthcare workers that are at risk throughout the
      hospital medication system.

PMID- 22953212
TI  - Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by
      Inhalation Exposure in Rats.
AB  - OBJECTIVES: We sought to establish a novel method to generate nano-sized carbon
      black particles (nano-CBPs) with an average size smaller than 100 nm for
      examining the inhalation exposure risks of experimental rats. We also tested the
      effect of nano-CBPs on the pulmonary and circulatory systems. METHODS: We used
      chemical vapor deposition (CVD) without the addition of any additives to generate
      nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm
      to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose
      only inhalation chamber system for studying the inhalation toxicity in rats. The
      effect on the lungs and circulatory system was determined according to the degree
      of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The
      functional alteration of the hemostatic and vasomotor activities was measured by
      plasma coagulation, platelet activity, contraction and relaxation of blood
      vessels. RESULTS: Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats
      were exposed for 4 hour/day, 5 days/week for 4 weeks to 4.2 * 10(6), 6.2 * 10(5),
      and 1.3 * 10(5) particles/cm(3). Exposure of nano-CBPs by inhalation resulted in
      minimal pulmonary inflammation and did not appear to damage the lung tissue. In
      addition, there was no significant effect on blood functions, such as plasma
      coagulation and platelet aggregation, or on vasomotor function. CONCLUSION: We
      successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum
      concentration of 4.2 * 10(6) particles/cm(3) in a nose-only inhalation chamber
      system. This reliable method can be useful to investigate the biological and
      toxicological effects of inhalation exposure to nano-CBPs on experimental rats.

PMID- 22953213
TI  - Toxicity of Methylcyclohexane and Its Effect on the Reproductive System in SD
      Rats.
AB  - OBJECTIVES: There is limited data regarding the toxicity of methylcyclohexane,
      despite its wide use in rubber adhesives, paint diluents, and cleansing agents.
      This study aimed to verify the toxicity and influence on the reproductive system
      of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats.
      METHODS: Methylcyclohexane was injected subcutaneously into male and female SD
      rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100,
      and 1,000 mg/kg/day) for each group. The toxicity of testing material was
      verified by observing the change in body and organ weight, hematological change,
      pathological findings, and effect on the reproductive system at each different
      concentration. RESULTS: In the 1,000 mg/kg/day group, there were cases of animal
      deaths. In animals that survived, hematological changes, including a decrease in
      the red blood cell count, were observed. A considerable weight gain or loss and
      pathological abnormalities in the liver, kidney, and other organs were found.
      However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific
      abnormalities. In terms of reproductive toxicity, there were changes in hormone
      levels, including a significant decrease in hormones such as estradiol and
      progesterone (p < 0.001) in male animals. Menstrual cycle change for female
      animals did not show concentration dependency. CONCLUSION: When injected
      repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver,
      heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day,
      while the no observed adverse effect level was less than 100 mg/kg/day. The
      substance exerted little influence on the reproductive system.

PMID- 22953215
TI  - Perceived Working Conditions and Sickness Absence - A Four-year Follow-up in the
      Food Industry.
AB  - OBJECTIVES: To analyze the association between changes in perceived physical and
      psychosocial working conditions and change of sickness absence days in younger
      and older (< 50 and >= 50 years) food industry employees. METHODS: This was a
      follow up study of 679 employees, who completed working conditions survey
      questionnaires in 2005 and 2009 and for whom the requisite sickness absence data
      were available for the years 2004 and 2008. RESULTS: Sickness absence increased
      and working conditions improved during follow-up. However, the change of
      increased sickness absence days were associated with the change of increased poor
      working postures and the change of deteriorated team spirit and reactivity
      (especially among < 50 years). No other changes in working conditions were
      associated with the changes in sickness absence. CONCLUSION: Sickness absence is
      affected by many factors other than working conditions. Nevertheless, according
      to this study improving team spirit and reactivity and preventing poor working
      postures are important in decreasing sickness absence.

PMID- 22953214
TI  - Exploring occupational and behavioral risk factors for obesity in firefighters: a
      theoretical framework and study design.
AB  - Firefighters and police officers have the third highest prevalence of obesity
      among 41 male occupational groups in the United States (US). However, few studies
      have examined the relationship of firefighter working conditions and health
      behaviors with obesity. This paper presents a theoretical framework describing
      the relationship between working conditions, health behaviors, and obesity in
      firefighters. In addition, the paper describes a detailed study plan for
      exploring the role of occupational and behavioral risk factors in the development
      of obesity in firefighters enrolled in the Orange County Fire Authority Wellness
      Fitness Program. The study plan will be described with emphasis on its
      methodological merits: adopting a participatory action research approach,
      developing a firefighter-specific work and health questionnaire, conducting both
      a cross-sectional epidemiological study using the questionnaire and a sub-study
      to assess the validity of the questionnaire with dietary intake and physical
      activity measures, and evaluating the strengths and weaknesses of the body mass
      index as an obesity measure in comparison to skinfold-based percent body fat. The
      study plan based on a theoretical framework can be an essential first step for
      establishing effective intervention programs for obesity among professional and
      voluntary firefighters.

PMID- 22953216
TI  - An empirical analysis on labor unions and occupational safety and health
      committees' activity, and their relation to the changes in occupational injury
      and illness rate.
AB  - OBJECTIVES: To find out from an analysis of empirical data the levels of
      influence, which a labor union (LU) and Occupational Safety and Health Committee
      (OSHC) have in reducing the occupational injury and illness rate (OIIR) through
      their accident prevention activities in manufacturing industries with five or
      more employees. METHODS: The empirical data used in this study are the
      Occupational Safety and Health Tendency survey data, Occupational Accident
      Compensation data and labor productivity and sales data for the years 2003 to
      2007. By matching these three sources of data, a final data set (n = 280) was
      developed and analyzed using SPSS version 18 (SPSS Inc., Chicago, IL, USA).
      RESULTS: It was found that a workplace with a LU has a lower OIIR than one
      without a LU. In manufacturing industries with five or more employees in 2007,
      the OIIR of the workplaces without a LU was 0.87%, while that of workplaces with
      a LU was much lower at 0.45%. In addition, workplaces with an established OSHC
      had a lower OIIR than those without an OSHC. CONCLUSION: It was found that the
      OIIR of workplaces with a LU is lower than those without a LU. Moreover, those
      with the OSHC usually had a lower OIIR than those without. The workplace OIIR may
      have an impact on management performance because the rate is negatively
      correlated with labor productivity and sales. In the long run, the OIIR of
      workplaces will be reduced when workers and employers join forces and recognize
      that the safety and health activities of the workplace are necessary, not only
      for securing the health rights of the workers, but also for raising labor
      productivity.

PMID- 22953217
TI  - Facilitators and Barriers in the Use of a Checklist by Insurance Physicians
      during Work Ability Assessments in Depressive Disorder.
AB  - OBJECTIVES: Depressive disorder (DD) is a complex disease, and the assessment of
      work ability in patients with DD is also complicated. The checklist depression
      (CDp) has recently been developed to support such work ability assessments and
      has been recommended for implementation in insurance medicine, starting with an
      analysis of the organisational and social contexts. The aim of this study was to
      identify the potential facilitators and barriers in the use of the CDp by
      insurance physicians (IPs) during work ability assessments of employees on sick
      leave due to DD. METHODS: A qualitative research was conducted based on semi
      structured interviews. The participants were IPs with at least one year of work
      experience in performing work ability assessments. The interviews were
      audiotaped, transcribed and analysed qualitatively. RESULTS: Ten IPs (7 males, 3
      females; mean 53 years) were interviewed. Important facilitators, which emerged
      for use of the CDp, were an oral introduction for colleagues and staff, support
      from management, valuing the increased transparency in work ability assessments
      with using the CDp, having adequate time for assessments as well as modification
      of the appearance (colour, plasticised form) and content (clarifying aspects of
      the examples) of the assessment tool. The fear of the loss of autonomy, lack of
      added value of the CDp, high workload, inadequate instructions and lack of time
      were mentioned as barriers. CONCLUSION: Adequate introduction to the use of CDp
      and the fear of the loss of autonomy of IPs need special attention in planning
      its implementation.

PMID- 22953218
TI  - The Risk Rating System for Noise-induced Hearing Loss in Korean Manufacturing
      Sites Based on the 2009 Survey on Work Environments.
AB  - OBJECTIVES: In Korea, an average of 258 workers claim compensation for their
      noise-induced hearing loss (NIHL) on an annual basis. Indeed, hearing disorder
      ranks first in the number of diagnoses made by occupational medical check-ups.
      Against this backdrop, this study analyzed the impact of 19 types of noise
      generating machines and equipment on the sound pressure levels in workplaces and
      NIHL occurrence based on a 2009 national survey on work environments. METHODS:
      Through this analysis, a series of statistical models were built to determine
      posterior probabilities for each worksite with an aim to present risk ratings for
      noise levels at work. RESULTS: It was found that air compressors and grinding
      machines came in first and second, respectively in the number of installed noise
      generating machines and equipment. However, there was no direct relationship
      between workplace noise and NIHL among workers since noise-control equipment and
      protective gear had been in place. By building a logistic regression model and
      neural network, statistical models were set to identify the influence of the
      noise-generating machines and equipment on workplace noise levels and NIHL
      occurrence. CONCLUSION: This study offered NIHL prevention measures which are fit
      for the worksites in each risk grade.

PMID- 22953219
TI  - Noise exposure assessment in a dental school.
AB  - OBJECTIVES: This cross-sectional study was performed in the Dental School of
      Prince of Songkla University to ascertain noise exposure of dentists, dental
      assistants, and laboratory technicians. A noise spectral analysis was taken to
      illustrate the spectra of dental devices. METHODS: A noise evaluation was
      performed to measure the noise level at dental clinics and one dental laboratory
      from May to December 2010. Noise spectral data of dental devices were taken
      during dental practices at the dental services clinic and at the dental
      laboratory. A noise dosimeter was set following the Occupational Safety and
      Health Administration criteria and then attached to the subjects' collar to
      record personal noise dose exposure during working periods. RESULTS: The peaks of
      the noise spectrum of dental instruments were at 1,000, 4,000, and 8,000 Hz which
      depended on the type of instrument. The differences in working areas and job
      positions had an influence on the level of noise exposure (p < 0.01). Noise
      measurement in the personal hearing zone found that the laboratory technicians
      were exposed to the highest impulsive noise levels (137.1 dBC). The dentists and
      dental assistants who worked at a pedodontic clinic had the highest percent noise
      dose (4.60 +/- 3.59%). In the working areas, the 8-hour time-weighted average of
      noise levels ranged between 49.7-58.1 dBA while the noisiest working area was the
      dental laboratory. CONCLUSION: Dental personnel are exposed to noise intensities
      lower than occupational exposure limits. Therefore, these dental personnel may
      not experience a noise-induced hearing loss.

PMID- 22953221
TI  - The Effects of Long-Term, Low-Level Exposure to Monocyclic Aromatic Hydrocarbons
      on Worker's Insulin Resistance.
AB  - OBJECTIVES: This study was designed to investigate whether long-term, low-level
      exposure to monocyclic aromatic hydrocarbons (MAHs) induced insulin resistance.
      METHODS: The subjects were 110 male workers who were occupationally exposed to
      styrene, toluene, and xylene. One hundred and ten age-matched male workers who
      had never been occupationally exposed to organic solvents were selected as a
      control group. Cytokines, which have played a key role in the pathogenesis of
      insulin resistance, and oxidative stress indices were measured. Assessment of
      exposure to MAHs was performed by measuring their ambient levels and their
      urinary metabolites in exposed workers, and the resulting parameters between the
      exposed group and non-exposed control groups were compared. RESULTS: There was no
      significant difference in general characteristics and anthropometric parameters
      between the two groups; however, total cholesterol, fasting glucose, fasting
      insulin, and homeostasis model assessment of insulin resistance levels were
      significantly higher in the exposed group. Phenylglyoxylic acid levels showed
      significant association with tumor necrosis factor-alpha, total oxidative status,
      and oxidative stress index via multiple linear regression analysis. Further,
      there was a negative correlation between methylhippuric acid levels and total
      anti-oxidative capacity, and there was a significant relationship between MAHs
      exposure and fasting glucose levels, as found by multiple logistic regression
      analysis (odds ratio = 3.95, 95% confidence interval = 1.074-14.530). CONCLUSION:
      This study indicated that MAHs increase fasting glucose level and insulin
      resistance. Furthermore, these results suggested that absorbing the organic
      solvent itself and active metabolic intermediates can increase oxidative stress
      and cytokine levels, resulting in the changes in glucose metabolism and the
      induction of insulin resistance.

PMID- 22953220
TI  - Odor thresholds and breathing changes of human volunteers as consequences of
      sulphur dioxide exposure considering individual factors.
AB  - OBJECTIVES: Though sulfur dioxide (SO(2)) is used widely at workplaces,
      itseffects on humans are not known. Thresholds are reported without reference to
      gender or age and occupational exposure limits are basedon effects on lung
      functioning,although localized effects in the upper airways can be expected.This
      study's aim is to determine thresholds with respect to age and gender and
      suggests a new approach to risk assessment using breathing reflexes presumably
      triggered by trigeminal receptors in the upper airways. METHODS: Odor thresholds
      were determined by the ascending method of limits in groups stratified by age and
      gender.Subjects rated intensities of different olfactory and trigeminal
      perceptions at different concentrations of SO(2). During the presentation of the
      concentrations, breathing movements were measured by respiratory inductive
      plethysmography. RESULTS: Neither age nor gender effects were observed for odor
      threshold. Only ratings of nasal irritation were influenced bygender. A benchmark
      dose analysis on relative respiratory depth revealed a 10%-deviation from
      baseline at about 25.27 mg/m(3). CONCLUSION: The proposed new approach to risk
      assessment appearsto be sustainable. We discuss whether a 10%-deviation of
      breathingdepth is relevant.

PMID- 22953222
TI  - Banding the world together; the global growth of control banding and qualitative
      occupational risk management.
AB  - Control Banding (CB) strategies to prevent work-related illness and injury for
      2.5 billion workers without access to health and safety professionals has grown
      exponentially this last decade. CB originates from the pharmaceutical industry to
      control active pharmaceutical ingredients without a complete toxicological basis
      and therefore no occupational exposure limits. CB applications have broadened
      into chemicals in general - including new emerging risks like nanomaterials and
      recently into ergonomics and injury prevention. CB is an action-oriented
      qualitative risk assessment strategy offering solutions and control measures to
      users through "toolkits". Chemical CB toolkits are user-friendly approaches used
      to achieve workplace controls in the absence of firm toxicological and
      quantitative exposure information. The model (technical) validation of these
      toolkits is well described, however firm operational analyses (implementation
      aspects) are lacking. Consequentially, it is often not known if toolkit use leads
      to successful interventions at individual workplaces. This might lead to virtual
      safe workplaces without knowing if workers are truly protected. Upcoming
      international strategies from the World Health Organization Collaborating Centers
      request assistance in developing and evaluating action-oriented procedures for
      workplace risk assessment and control. It is expected that to fulfill this
      strategy's goals, CB approaches will continue its important growth in protecting
      workers.

PMID- 22953223
TI  - Diabetes management and hyperglycemia in safety sensitive jobs.
AB  - The chronic and acute effects of hyperglycemia affecting cognition and work are
      as important as those of hypoglycemia. Its impact, considering that majority of
      diabetic patients fail to reach therapeutic targets, would be potentially
      significant. Self monitoring of blood glucose, recognition of body cues and
      management interventions should be geared not only towards avoidance of disabling
      hypoglycemia, but also towards unwanted hyperglycemia. Over the long term,
      chronic hyperglycemia is a risk for cognitive decline. Acute episodes of
      hyperglycemia, above 15 mmol/L have also been shown to affect cognitive motor
      tasks. Maintaining blood sugar to avoid hyperglycemia in diabetic workers will
      help promote safety at work.

PMID- 22953224
TI  - The occupational exposure limit for fluid aerosol generated in metalworking
      operations: limitations and recommendations.
AB  - The aim of this review was to assess current knowledge related to the
      occupational exposure limit (OEL) for fluid aerosols including either mineral or
      chemical oil that are generated in metalworking operations, and to discuss
      whether their OEL can be appropriately used to prevent several health risks that
      may vary among metalworking fluid (MWF) types. The OEL (time-weighted average; 5
      mg/m(3), short-term exposure limit ; 15 mg/m(3)) has been applied to MWF aerosols
      without consideration of different fluid aerosol-size fractions. The OEL, is also
      based on the assumption that there are no significant differences in risk among
      fluid types, which may be contentious. Particularly, the health risks from
      exposure to water-soluble fluids may not have been sufficiently considered.
      Although adoption of The National Institute for Occupational Safety and Health's
      recommended exposure limit for MWF aerosol (0.5 mg/m(3)) would be an effective
      step towards minimizing and evaluating the upper respiratory irritation that may
      be caused by neat or diluted MWF, this would fail to address the hazards (e.g.,
      asthma and hypersensitivity pneumonitis) caused by microbial contaminants
      generated only by the use of water-soluble fluids. The absence of an OEL for the
      water-soluble fluids used in approximately 80-90 % of all applicants may result
      in limitations of the protection from health risks caused by exposure to those
      fluids.

PMID- 22953225
TI  - Lead poisoning: historical aspects of a paradigmatic "occupational and
      environmental disease".
AB  - Lead poisoning is one of the earliest identified and most known occupational
      disease. Its acute effects have been recognized from antiquity when this
      condition principally afflicted manual workers and slaves, actually scarcely
      considered by the medicine of that time. The Industrial Revolution caused an
      epidemic of metal intoxication, urging scientists and physician of that period to
      study and identify specific symptoms and organ alterations related to chronic
      lead poisoning. During the 20th century, the acknowledgment of occupational and
      environmental toxicity of lead fostered public awareness and legislation to
      protect health. More recently, the identification of sub-clinical effects have
      greatly modified the concept of lead poisoning and the approaches of medicine
      towards this condition. Nowadays, lead poisoning is rarely seen in developed
      countries, but it still represents a major environmental problem in certain
      areas. Consequently, it may appear as a paradigm of "occupational and
      environmental disease," and the history of this condition seems to parallel the
      historical development of modern "Occupational and Environmental Health" as a
      more complete medical discipline.

PMID- 22953226
TI  - Association of biomarker levels with severity of asbestos-related diseases.
AB  - OBJECTIVES: Asbestos-related diseases (ARDs) have increased globally over the
      decades, causing an economic burden and increased health care costs. It is
      difficult to predict the risk of development of ARDs and of respiratory
      disability among workers with a history of asbestos exposure. Blood based
      biomarkers have been reported as promising tools for the early detection of
      malignant mesothelioma. This study investigated whether serum soluble mesothelin
      related peptide (SMRP) would reflect severity of disablement in compensable ARDs.
      METHODS: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects.
      Severity of ARDs was assessed by a Medical Authority comprising four specially
      qualified respiratory physicians. Severity of ARDs and SMRP levels were compared.
      RESULTS: Mean (standard deviation) serum SMRP level in the population with
      compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated
      with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos
      exposed subjects was significantly lower than those with pleural plaques (p <
      0.0001) and in subjects with ARDs who received compensation (p < 0.01).
      CONCLUSION: This study indicates that serum SMRP levels correlate with severity
      of compensable ARDs. Serum SMRP could potentially be applied to monitor progress
      of ARDs. Further prospective work is needed to confirm the relationship between
      SMRP and disability assessment in this population.

PMID- 22953227
TI  - Comparison of Three Different Slip Meters under Various Contaminated Conditions.
AB  - OBJECTIVES: To challenge the problem of slipperiness, various slipmeters have
      been developed to assess slip hazard. The performance of in-situ slipmeter is,
      however, still unclear under the various floor conditions. The main objectives of
      this study were to evaluate the performance of three kinds of slipmeters under
      real conditions, and to find their dynamic and kinematic characteristics, which
      were compared with gait test results. METHODS: Four common restaurant floor
      materials were tested under five contaminants. Slipmeters and human gaits were
      measured by high speed camera and force plate to find and compare their dynamic
      and kinematic characteristics. RESULTS: The contact pressures and built-up ratio
      were below those of subjects. The sliding velocity of British Pendulum Tester was
      above those of subjects, while those of BOT-3000 and English XL were below those
      of subjects. From the three meters, the English XL showed the highest overall
      correlation coefficient (r = 0.964) between slip index and R(a), while the rest
      did not show statistical significance with surface roughness parameters (R(a),
      R(z)). The English XL only showed statistical significance (p < 0.01) between
      slip index and contaminants. The static coefficient of friction obtained with the
      BOT-3000 showed good consistency and repeatability (CV < 0.1) as compared to the
      results for the BPT (CV > 0.2) and English XL (CV < 0.2). CONCLUSION: It is
      unclear whether surface roughness can be a reliable and objective indicator of
      the friction coefficient under real floor conditions, and the viscosity of
      contaminants can affect the friction coefficient of the same floors. Therefore,
      to evaluate slipperiness, the performance of the slipmeters needed to improve.

PMID- 22953228
TI  - Assessment of muscle fatigue associated with prolonged standing in the workplace.
AB  - OBJECTIVES: The objectives of this study were to determine the psychological
      fatigue and analyze muscle activity of production workers who are performing
      processes jobs while standing for prolonged time periods. METHODS: The
      psychological fatigue experienced by the workers was obtained through
      questionnaire surveys. Meanwhile, muscle activity has been analyzed using surface
      electromyography (sEMG) measurement. Lower extremities muscles include: erector
      spinae, tibialis anterior, and gastrocnemius were concurrently measured for more
      than five hours of standing. Twenty male production workers in a metal stamping
      company participated as subjects in this study. The subjects were required to
      undergo questionnaire surveys and sEMG measurement. RESULTS: Results of the
      questionnaire surveys found that all subjects experienced psychological fatigue
      due to prolonged standing jobs. Similarly, muscle fatigue has been identified
      through sEMG measurement. Based on the non-parametric statistical test using the
      Spearman's rank order correlation, the left erector spinae obtained a moderate
      positive correlation and statistically significant (r(s) = 0.552, p < 0.05)
      between the results of questionnaire surveys and sEMG measurement. CONCLUSION:
      Based on this study, the authors concluded that prolonged standing was
      contributed to psychological fatigue and to muscle fatigue among the production
      workers.

PMID- 22953230
TI  - Tracing new occupational diseases, an introduction.

PMID- 22953229
TI  - European approaches to work-related stress: a critical review on risk evaluation.
AB  - In recent years, various international organizations have raised awareness
      regarding psychosocial risks and work-related stress. European stakeholders have
      also taken action on these issues by producing important documents, such as
      position papers and government regulations, which are reviewed in this article.
      In particular, 4 European models that have been developed for the assessment and
      management of work-related stress are considered here. Although important
      advances have been made in the understanding of work-related stress, there are
      still gaps in the translation of this knowledge into effective practice at the
      enterprise level. There are additional problems regarding the methodology in the
      evaluation of work-related stress. The European models described in this article
      are based on holistic, global and participatory approaches, where the active role
      of and involvement of workers are always emphasized. The limitations of these
      models are in the lack of clarity on preventive intervention and, for two of
      them, the lack of instrument standardization for risk evaluation. The comparison
      among the European models to approach work-related stress, although with
      limitations and socio-cultural differences, offers the possibility for the
      development of a social dialogue that is important in defining the correct and
      practical methodology for work stress evaluation and prevention.

PMID- 22953231
TI  - Occupational lifting tasks and retinal detachment in non-myopics and myopics:
      extended analysis of a case-control study.
AB  - OBJECTIVES: Lifting heavy weights involves the Valsalva manoeuvre, which leads to
      intraocular pressure spikes. We used data from a case-control study to further
      investigate the hypothesis that occupational lifting is a risk factor for retinal
      detachment. METHODS: The study population included 48 cases (patients operated
      for retinal detachment) and 84 controls (outpatients attending an eye clinic).
      The odds ratios (OR) of idiopathic retinal detachment were estimated with a
      logistic regression model (adjusted for age, sex and body mass index). Three
      indexes were used to examine exposure to lifting; 1) maximum load lifted, 2)
      average weekly lifting, 3) lifelong cumulative lifting. RESULTS: For all indexes,
      the most exposed subjects showed an increased risk of retinal detachment compared
      with the unexposed (index 1: OR 3.57, 95% confidence interval [CI] 1.21-10.48;
      index 2: OR 3.24, 95% CI 1.32-7.97; index 3: OR 2.23, 95% CI 1.27-8.74) and dose
      response relationships were apparent. CONCLUSION: These results reinforce the
      hypothesis that heavy occupational lifting may be a relevant risk factor for
      retinal detachment.

PMID- 22953232
TI  - Outbreak of sudden cardiac deaths in a tire manufacturing facility: can it be
      caused by nanoparticles?
AB  - OBJECTIVES: The purpose of this study was to review clinical characteristics and
      working environments of sudden cardiac death (SCD) cases associated with a tire
      manufacturer in Korea, and review possible occupational risk factors for
      cardiovascular disease including nanoparticles (ultrafine particles, UFPs).
      METHODS: We reviewed (i) the clinical course of SCD cases and (ii) occupational
      and non-occupational risk factors including chemicals, the physical work
      environment, and job characteristics. RESULTS: Possible occupational factors were
      chemicals, UFPs of rubber fume, a hot environment, shift work, overworking, and
      noise exposure. The mean diameter of rubber fume (63-73 nm) was (larger than
      diesel exhaust [12 nm] and outdoor dust [50 nm]). The concentration of carbon
      disulfide, carbon monoxide and styrene were lower than the limit of detection.
      Five SCD cases were exposed to shift work and overworking. Most of the cases had
      several non-occupational factors such as hypertension, overweight and smoking.
      CONCLUSION: The diameter of rubber fume was larger than outdoor and the diesel
      exhaust, the most well known particulate having a causal relationship with
      cardiovascular disease. The possibility of a causal relation between UFPs of
      rubber fume and SCD was not supported in this study. However, it is necessary to
      continue studying the relationship between large sized UFPs and SCD.

PMID- 22953233
TI  - Surveillance Programme of Work-related Diseases (WRD) in France.
AB  - The surveillance programme of work-related diseases (WRD) is based on a network
      of occupational physicians who notify all WRD diagnosed during a two-week
      observation period. The aims are mainly to estimate the prevalence of non
      compensated WRD in the working population according to socio economic factors; to
      determine new indicators of occupational health; to update the lists of
      compensable occupational diseases; to understand and assess under-compensation
      and under-notification. The participation rate for occupational physicians is
      around 33% in 2008. The main WRD are the musculoskeletal disorders, followed by
      the mental disorders. This 2-week protocol, repeated regularly, provides useful
      data on frequency of pathologies linked to employment as well as an estimate of
      unreported WRD subject to compensation or non-compensated WRDs, and the trends of
      WRDs over the time.

PMID- 22953234
TI  - OccIDEAS: An Innovative Tool to Assess Past Asbestos Exposure in the Australian
      Mesothelioma Registry.
AB  - Malignant mesothelioma is an uncommon but rapidly fatal disease for which the
      principal aetiological agent is exposure to asbestos. Mesothelioma is of
      particular significance in Australia where asbestos use was very widespread from
      the 1950s until the 1980s. Exposure to asbestos includes occupational exposure
      associated with working with asbestos or in workplaces where asbestos is used and
      also 'take-home' exposure of family members of asbestos exposed workers. Asbestos
      exposure may also be non-occupational, occurring as a consequence of using
      asbestos products in non-occupational contexts and passive exposure is also
      possible, such as exposure to asbestos products in the built environment or
      proximity to an environmental source of exposure, for example an asbestos
      production plant. The extremely long latency period for this disease makes
      exposure assessment problematic in the context of a mesothelioma registry.
      OccIDEAS, a recently developed online tool for retrospective exposure assessment,
      has been adapted for use in the Australian Mesothelioma Registry (AMR) to enable
      systematic retrospective exposure assessment of consenting cases. Twelve
      occupational questionnaire modules and one non-occupational module have been
      developed for the AMR, which form the basis of structured interviews using
      OccIDEAS, which also stores collected data and provides a framework for
      generating metrics of exposure.

PMID- 22953235
TI  - Emerging zoonoses: the "one health approach".
AB  - Zoonoses represent a public health risk recently pointed out by the spreading of
      previously unknown human infectious diseases emerging from animal reservoirs such
      as severe acute respiratory syndrome and avian influenza caused by H5N1-virus.
      These outbreaks have shown that animal breeding activities can pose a significant
      public health risk. Until now, the risk of zoonoses has probably been
      underestimated, particularly in occupational settings. The emergence or re
      emergence of bacterial (Mycobacterium bovis and Brucella spp) or viral (hepatitis
      E virus) infections shows that zoonoses should be considered as emerging risks in
      agricultural and animal breeding and should be addressed by specific preventive
      interventions. Close cooperation and interaction between veterinarians,
      occupational health physicians and public health operators is necessary, for a
      worldwide strategy to expand interdisciplinary collaborations and communications
      in all aspects of health care for humans, animals and the environment. This is
      what the One Health Approach was intended to be.

PMID- 22953236
TI  - Local Public Health System Response to the Tsunami Threat in Coastal California
      following the Tohoku Earthquake.
AB  - Background On Friday March 11, 2011 a 9.0 magnitude earthquake triggered a
      tsunami off the eastern coast of Japan, resulting in thousands of lives lost and
      billions of dollars in damage around the Pacific Rim. The tsunami first reached
      the California coast on Friday, March 11th, causing more than $70 million in
      damage and at least one death. While the tsunami's impact on California pales in
      comparison to the destruction caused in Japan and other areas of the Pacific, the
      event tested emergency responders' ability to rapidly communicate and coordinate
      a response to a potential threat. Methods To evaluate the local public health
      system emergency response to the tsunami threat in California, we surveyed all
      local public health, emergency medical services (EMS), and emergency management
      agencies in coastal or floodplain counties about several domains related to the
      tsunami threat in California, including: (1) the extent to which their community
      was affected by the tsunami, (2) when and how they received notification of the
      event, (3) which public health response activities were carried out to address
      the tsunami threat in their community, and (4) which organizations contributed to
      the response. Public health activities were characterized using the Centers for
      Disease Control and Prevention (CDC) Public Health Preparedness Capabilities
      (PHEP) framework. Findings The tsunami's impact on coastal communities in
      California ranged widely, both in terms of the economic consequences and the
      response activities. Based on estimates from the National Oceanic and Atmospheric
      Administration (NOAA), ten jurisdictions in California reported tsunami-related
      damage, which ranged from $15,000 to $35 million. Respondents first became aware
      of the tsunami threat in California between the hours of 10:00pm Pacific Standard
      Time (PST) on Thursday March 10th and 2:00pm PST on Friday March 11th, a range of
      16 hours, with notification occurring through both formal and informal channels.
      In response to this threat, the activities most commonly reported by the local
      government agencies included in this study were: emergency public information and
      warning, emergency operations coordination, and inter-organizational information
      sharing, which were reported by 86%, 75%, and 65% of all respondents,
      respectively. When looking at the distribution of responsibility, emergency
      management agencies were the most likely to report assuming a lead role in these
      common activities as well as those related to evacuation and community recovery.
      While activated less frequently, public health agencies carried out emergency
      response functions related to surveillance and epidemiology, environmental
      health, and mental health/psychological support. Both local public health and EMS
      agencies took part in mass care and medical material management activities. A
      large network of organizations contributed to response activities, with emergency
      management, law enforcement, fire, public health, public works, EMS, and media
      cited by more than half of respondents. Conclusions In response to the tsunami
      threat in California, we found that emergency management agencies assumed a lead
      role in the local response efforts. While public health and medical agencies
      played a supporting role in the response, they uniquely contributed to a number
      of specific activities. If the response to the recent tsunami is any indication,
      these support activities can be anticipated in planning for future events with
      similar characteristics to the tsunami threat. Additionally, we found that many
      respondents first learned of the tsunami through the media, rather than through
      rapid notification systems, which suggests that government agencies must continue
      to develop and maintain the ability to rapidly aggregate and analyze information
      in order to provide accurate assessments and guidance to a potentially well
      informed public. CITATION: Hunter JC, Crawley AW, Petrie M, Yang JE, Aragon TJ.
      Local Public Health System Response to the Tsunami Threat in Coastal California
      following the Tohoku Earthquake. PLoS Currents Disasters. 2012 Jul 16.

PMID- 22953237
TI  - Intrastriatal transplantation of neurotrophic factor-secreting human mesenchymal
      stem cells improves motor function and extends survival in R6/2 transgenic mouse
      model for Huntington's disease.
AB  - Stem cell-based treatment for Huntington's disease (HD) is an expanding field of
      research. Although various stem cells have been shown to be beneficial in vivo,
      no long standing clinical effect has been demonstrated. To address this issue, we
      are developing a stem cell-based therapy designed to improve the microenvironment
      of the diseased tissue via delivery of neurotrophic factors (NTFs). Previously,
      we established that bone marrow derived human mesenchymal stem cells (MSCs) can
      be differentiated using medium based cues into NTF-secreting cells (NTF+ cells)
      that express astrocytic markers. NTF+ cells were shown to alleviate
      neurodegeneration symptoms in several disease models in vitro and in vivo,
      including the model for excitotoxicity. In the present study, we explored if the
      timing of intrastriatal transplantation of hNTF+ cells into the R6/2 transgenic
      mouse model for HD influences motor function and survival. One hundred thousand
      cells were transplanted bilaterally into the striatum of immune-suppressed mice
      at 4.5, 5.5 and 6.5 weeks of age. Contrary to our expectations, early
      transplantation of NTF+ cells did not improve motor function or overall survival.
      However, late (6.5 weeks) transplantation resulted in a temporary improvement in
      motor function and an extension of life span relative to that observed for PBS
      treated mice. We conclude that late transplantation of NTF+ cells induces a
      beneficial effect in this transgenic model for HD. Since no transplanted NTF+
      cells could be detected in vivo, we suspect that the temporary nature of the
      beneficial effect is due to poor survival of transplanted cells. In general, we
      submit that NTF+ cells should be further evaluated for the therapy of HD.

PMID- 22953239
TI  - 2012-2025 Roadmap of I.R.Iran's Disaster Health Management.
AB  - OBJECTIVE: In line with Iran's Comprehensive Health Sector Road Map, the National
      Institute of Health Research at the Tehran University of Medical Sciences
      developed the 2012-2025 road map of Disaster Health Management (DHM), including
      goals and objectives, strategies, activities and related prerequisites. This
      article presents the process and results of this road mapping project. METHODS:
      The project started with an expanded literature review followed by stakeholder
      analysis to assess level of interest and impact of related organizations to DHM;
      STEEP.V methodology to define determinants with a potential impact on Iran's HDM
      for duration of 2012 to 2025; strength, weakness, opportunity and threat (SWOT)
      analysis and formulation of goals and objectives, strategies, activities, and
      prerequisites. Brainstorming, group discussion and interviews with key informants
      were used for data collection; nominal group technique was used whenever
      prioritization was necessary, and Delphi panel methodology was applied for
      consensus development. RESULTS: STEEP.V analysis revealed the most important
      Social, Technological, Environmental, Economic, Political and Value-based
      determinants. Iran's DHM mission and vision were defined respectively as
      "Mitigation from, preparedness for, response to and recovery from consequences of
      natural and man-made hazards at the community level as well as to the health
      facilities and resources of I.R.Iran" and "In 2025, Iran's DHM will be the most
      developed system in the region resulting in the least vulnerability, the highest
      readiness in health facilities and resources, and the highest and most effective
      contribution of the Iranian community to disaster resilience", respectively.
      Sixteen strategies and related activities, along with the necessary
      prerequisites, were developed. CONCLUSIONS: This was the first attempt at
      comprehensive strategic planning in the field of DHM in Iran. The current
      framework provides Iran's health system with a list of strategies and activities
      to be considered in operational planning and actions. However, a dynamic process
      of evaluation and revision is required to ensure that Iran's health system goals
      are met by 2025. Address for correspondence: Ali Ardalan, No. 78, Italia Ave,
      Department of Disaster and Emergency Health, National Institute of Health
      Research, Tehran University of Medical Sciences, Tehran, Iran. Email:
      aardalan@gmail.com or aardalan@tums.ac.ir CITATION: Ardalan A, Rajaei MH, Masoumi
      G, Azin A, Zonoobi V, Sarvar M, Vaskoei Eshkevari K, Ahmadnezhad E, Jafari G.
      2012-2025 Roadmap of I.R.Iran's Disaster Health Management. PLoS Currents
      Disasters. 2012 Jul 16.

PMID- 22953238
TI  - The Prevalence of Juvenile Huntington's Disease: A Review of the Literature and
      Meta-Analysis.
AB  - Juvenile Huntington's disease (JHD) is usually defined as Huntington's disease
      with an onset <= 20 years. The proportion of JHD cases reported in studies of
      Huntington's disease (HD) varies. A review of the literature found 62 studies
      that reported the proportion of JHD cases amongst all HD cases. The proportion of
      JHD cases in these studies ranged from 1% to 15%, and in a meta-analysis the
      pooled proportion of JHD cases was 4.92% (95% confidence interval of 4.07% to
      5.84%). Limiting the analysis to the 25 studies which used multiple methods of
      ascertainment resulted in a similar pooled proportion of 5.32%, (95% confidence
      interval 4.18% to 6.60%). A small difference was observed when the meta-analysis
      was restricted to studies from countries defined by the World Bank as high
      income, that used multiple methods of ascertainment, and that were conducted
      since 1980 (4.81%, 95% confidence interval 3.31% to 6.58%, n=11). This contrasts
      with the pooled result from three post 1980 studies using multiple methods of
      ascertainment from South Africa and Venezuela, defined by the World Bank as upper
      middle income, where the estimated mean proportion was 9.95%, (95% confidence
      interval 6.37% to 14.22%). These results, which are expected to be more robust
      than those from a single study alone, may be helpful in estimating the proportion
      of JHD cases in a given population. Key Words: Juvenile Huntington's disease,
      prevalence, epidemiology.

PMID- 22953240
TI  - Knowledge, Attitude and Practice of Tehran's Inhabitants for an Earthquake and
      Related Determinants.
AB  - Background A major destructive earthquake is predicted to shake the Tehran city
      in the near future. To mitigate the damage from such earthquakes, it is necessary
      to assess the preparedness of people and find the related risk factors. Methods A
      cross-sectional study was conducted in Tehran city among people aged 15 years or
      older in 2009. 1195 of Tehran's residents were interviewed using a questionnaire.
      Pearson chi-square test and binary logistic regression were used in order to
      evaluate the factors associated with preparedness against an earthquake. Results
      The analysis showed that 1076 (90.0%), 1160 (97.1%), and 490 (41.0%) of the
      participants achieved half of the possible scores for the knowledge, attitude,
      and practice components, respectively. Furthermore, in multivariate analysis low
      knowledge (p<0.001), having a high-school (p=0.033) or lower education (p<0.001)
      and living in Northern high-risk regions (p<0.001) of the Tehran were identified
      as risk factors for taking precautionary measures against earthquake. For low
      knowledge, lack of previous experience (p<0.001), and working as labor,
      businessman, employee (p=0.001) or being housewife (p=0.002) were related risk
      factors. In addition, people in the Southern high risk regions were significantly
      more knowledgeable (OR=0.618 compared to people in low risk regions) about
      earthquakes. Conclusions It is suggested that preparedness programs should target
      people with lower educational level and people in high risk regions especially
      the Northern districts of the city and aim at increasing public knowledge about
      earthquakes. Address for correspondence: Ali Ardalan, No. 78, Italia Ave,
      Department of Disaster Public Health, School of Public Health, Tehran University
      of Medical Sciences, Tehran, Iran. Email: aardalan@gmail.com or
      aardalan@tums.ac.ir CITATION: Ostad Taghizadeh A, Hosseini M, Navidi I, Mahaki
      AA, Ammari H, Ardalan A. Knowledge, Attitude and Practice of Tehran's Inhabitants
      for an Earthquake and Related Determinants. PLOS Currents Disasters. 2012 Aug 6.

PMID- 22953241
TI  - Monitoring the mental well-being of caregivers during the Haiti-earthquake.
AB  - Introduction During disaster relief, personnel's safety is very important. Mental
      well being is a part of this safety issue. There is however a lack of objective
      mental well being monitoring tools, usable on scene, during disaster relief. This
      study covers the use of validated tools towards detection of psychological
      distress and monitoring of mental well being of disaster relief workers, during
      the Belgian First Aid and Support Team deployment after the Haiti earthquake in
      2010. Methodology The study was conducted using a demographic questionnaire
      combined with validated measuring instruments: Belbin Team Role, Compassion
      Fatigue and Satisfaction Self-Test for Helpers, DMAT PsySTART, K6+ Self Report. A
      baseline measurement was performed before departure on mission, and measurements
      were repeated at day 1 and day 7 of the mission, at the end of mission, and 7
      days, 30 days and 90 days post mission. Results 23 out of the 27 team members
      were included in the study. Using the Compassion Fatigue and Satisfaction Self
      Test for Helpers as a monitoring tool, a stable condition was monitored in 7
      participants, a dip in 5 participants, an arousal in 10 participants and a double
      pattern in 1 participant. Conclusions The study proved the ability to monitor
      mental well being and detect psychological distress, by self administered
      validated tools, during a real disaster relief mission. However for practical
      reasons some tools should be adapted to the specific use in the field. This study
      opens a whole new research area within the mental well being and monitoring
      field. CITATION: Van der Auwera M, Debacker M, Hubloue I. Monitoring the mental
      well-being of caregivers during the Haiti-earthquake.. PLoS Currents Disasters.
      2012 Jul 18.

PMID- 22953242
TI  - Weather and environmental hazards at mass gatherings.
AB  - Introduction Reviews of mass gathering events have traditionally concentrated on
      crowd variables that affect the level and type of medical care needed. Weather
      and environmental hazards at mass gathering events have not been fully
      researched. This review examines these events and aims to provide future
      suggestions for event organisers, medical resource planners, and emergency
      services, including local hospital emergency departments. Methods A review was
      conducted using computerised data bases: MEDLINE, The Cochrane Library, HMIC and
      EMBASE, with Google used to widen the search beyond peer-reviewed publications,
      to identify grey literature. All peer-review literature articles found containing
      information pertaining to lessons identified from mass gathering disasters due to
      weather or environmental hazards leading to participant death, injury or illness
      were analysed and reviewed. Disasters occurring due to crowd variables were not
      included. These articles were read, analysed, abstracted and summarised. Results
      20 articles from literature search were found detailing mass gathering disasters
      relating directly to weather or environmental hazards from 1988 - 2011, with only
      17 cases found within peer-review literature. Two events grey literature from
      2011 are due to undergo further inquiry while one article reviews an event
      originally occurring in 1922. Analysis of cases were categorised in to heat and
      cold-related events, lightning and storms and disease outbreak. Conclusions Mass
      gathering events have an enormous potential to place a severe strain on the local
      health care system, Prior health resource and environmental planning for heat &
      cold-related illness, lightning & storms, and disease outbreak can advance
      emergency preparedness and response to potential disasters. CITATION: Soomaroo L,
      Murray V. Weather and Environmental Hazards at Mass Gatherings. PLoS Currents
      Disasters. 2012 Jul 31 KEYWORDS: Mass Gatherings, Disasters, Sporting Events,
      Festivals, Concerts, Storm, Lightning, Cyclone, Hot-weather illness, Cold-weather
      illness, Disease, Public Health, Syndromic Surveillance Abbreviations: ALS -
      Advance Life support; BLS - Basic Life support; ED - Emergency Department; EMS -
      Emergency Medical Services; PPR - Patient Presentation Rate.

PMID- 22953244
TI  - APSP Journal of Case Reports: A New Beginning.

PMID- 22953243
TI  - Sensitization of tumor cells to cancer therapy by molecularly targeted inhibition
      of the inhibitor of nuclear factor kappaB kinase.
AB  - The inhibitor of nuclear factor kappaB kinase (IKK)-nuclear factor kappaB
      (NFkappaB) pathway is one of the most important cellular signal transduction
      pathways. It can be activated by diverse stimuli, resulting in liberation of
      cytoplasmic NFkappaB from inhibition by inhibitors of NFkappaB (IkappaB) after
      IkappaB are phosphorylated by IKKbeta and IKKalpha via the canonical and non
      canonical pathways, respectively. Activated NFkappaB then translocates into the
      nucleus to regulate various NFkappaB target genes. Through regulation of its
      target genes, NFkappaB can regulate various physiologic processes such as cell
      proliferation, migration and survival. More importantly, activation of the IKK
      NFkappaB pathway has been implicated in carcinogenesis, tumor development,
      progression and metastasis, and cancer resistance to radiotherapy and
      chemotherapy. Therefore, molecularly targeted inhibition of the different
      components of this pathway has been widely explored for treatment of cancer
      either alone or in combination with other cancer therapies. A growing body of
      evidence suggests that IKKbeta may be a better cancer treatment target in this
      pathway, because several novel NFkappaB-independent functions of IKKbeta have
      been identified recently, including promotion of DNA double strand break repair
      to increase tumor cell resistance to ionizing radiation and chemotherapy in an
      apoptosis-independent manner. In this review, we highlight some of these new
      findings and discuss the therapeutic potential of IKKbeta specific inhibitors as
      a novel tumor sensitizer.

PMID- 22953245
TI  - An unusual case of gastroschisis.
AB  - Gastroschisis is an abdominal wall defect through which intestine and rarely
      other organs eviscerate. It is less frequently associated with anorectal
      malformations. Abnormal size and shape of the defect is rarely identified in
      these patients. We report a case of gastroschisis with an unusual abdominal wall
      defect, imperforate anus and an ectopically placed vestibule. The defect was
      extended from right side of umbilicus to the perineum. There was evisceration of
      entire gastrointestinal tract (GIT), liver, gallbladder and urinary bladder. The
      defect was not manageable with a spring loaded silo and a sterilized blood bag
      was used to cover the defect. The unusual defect, associated anomalies and
      evisceration of unusual viscera are the main reasons for reporting the index
      case.

PMID- 22953246
TI  - Atresia of the ascending colon: a rarity.
AB  - Atresia of the colon is among the rare types of all gastrointestinal atresias.
      Ascending colon is the rarest site of all the colonic atresias. The authors
      report a case of a 4-day-old male baby who presented with the features of distal
      intestinal obstruction. At laparotomy type I atresia of the ascending colon, just
      distal to cecum, was found. Primary ceco-colic anastomosis along with a covering
      ileostomy was performed. Ileostomy was reversed 3 weeks later.

PMID- 22953247
TI  - Ileal duplication cyst causing recurrent abdominal pain and melena.
AB  - Alimentary tract duplications are rare congenital anomalies. The presentation
      depends on their anatomical location, size and other characteristics. The most
      common variety is small bowel cystic duplication. We report a case of an eight
      years old girl who presented with recurrent abdominal pain and melena.
      Radioisotope technetium scan showed increased uptake of tracer in right lower
      abdomen and a diagnosis of Meckel's diverticulum made. At surgery a cystic,
      communicating, ileal duplication found which was resected along with adjacent
      gut. It is thus reiterated that while investigating children with recurrent
      abdominal pain and melena, gut duplications must be included in the differential
      diagnosis.

PMID- 22953248
TI  - Delayed recognition of type 1 sigmoid-colon atresia: the perforated web variety.
AB  - Colonic atresias are the rare malformations of the colon and constitute about 1.7
      to 15% of all gastrointestinal (GI) atresias. A 6-month old infant presented with
      recurrent episodes of sub-acute intestinal obstruction since birth. During the
      index admission, patient had clinical signs of complete intestinal obstruction.
      The patient was operated and type I sigmoid-colon atresia found which on further
      exploration tuned out to be of perforated mucosal web variety. The resection of
      the involved part of colon and a primary end to oblique colo-colic anastomosis
      was performed.

PMID- 22953249
TI  - Gastric duplication cyst presenting as acute abdomen: a case report.
AB  - Gastric duplication cysts are rare variety of gastrointestinal duplications.
      Sometimes they may present with complications like hemorrhage, infection,
      perforation, volvulus, intussusception and rarely neoplastic changes in the
      gastric duplication cyst. We present one and half year old male child who
      developed sudden abdominal distension with pain and fever for two days.
      Ultrasound revealed a cystic mass in the hypochondrium and epigastric regions. On
      exploration an infected and perforated gastric duplication cyst was found.
      Surgical excision of most part of cyst wall with mucosal stripping of the rest
      was performed. Histopathology confirmed the diagnosis of gastric duplication
      cyst. Early surgical intervention can result in good outcome.

PMID- 22953250
TI  - A giant lymphatic cyst of the transverse colon mesentery.
AB  - Mesenteric cysts are not uncommon in pediatric age group but giant lymphatic
      cysts of mesentery are reported infrequently. This is a report of six years old
      female who had vague abdominal pain with distension for two years. Investigations
      revealed a large cystic mass in abdomen. On exploration a giant lymphatic cyst in
      the mesentery of transverse colon found. More than 1500 ml of milky fluid was
      drained. The cyst was unilocular and appeared to be the collection of lymph
      (chyle) between two leaves of the mesentery of transverse colon. It is postulated
      that trauma to or malformation of lymphatics at the root of mesentery might have
      lead to this pathology.

PMID- 22953251
TI  - Broken piece of silicone suction catheter in upper alimentary tract of a neonate.
AB  - Esophageal foreign bodies (FB) are common in adults and children. These are
      rarely reported in infants and neonates. A 2-day-old newborn was referred to our
      hospital with history of accidental intrusion of soft silicone suction catheter
      into the upper gastrointestinal tract (GIT). X-ray chest and abdomen confirmed
      the presence of suction tube in esophagus and stomach. The suction catheter was
      retrieved successfully at direct laryngoscopy.

PMID- 22953252
TI  - Hyposkillia and critical thinking: lost skills of doctors.

PMID- 22953253
TI  - Overlapping Features of Caudal Regression Syndrome and VACTERL Complex in a
      Neonate.

PMID- 22953254
TI  - Pancreatic calcification.

PMID- 22953255
TI  - Sirenomelia.

PMID- 22953256
TI  - A case for case report.

PMID- 22953257
TI  - Tracheal trifurcation associated with esophageal atresia.
AB  - We report a newborn with esophageal atresia (EA) in whom right tracheal bronchus
      (TB) and a tracheal diverticulum were identified intra-operatively. The right TB
      was further confirmed on MRI scan performed post-operatively. Such a tracheal
      trifurcation associated with EA has not been reported hitherto from Indian
      subcontinent.

PMID- 22953258
TI  - Pneumoscrotum: a rare presentation of gastric perforation in a neonate.
AB  - Pneumoperitoneum in neonates is not an uncommon condition. Free air in peritoneum
      may be secondary to host of pathological lesions. Usually the patient presents
      with signs of intraperitoneal sepsis, however presence of air in the scrotum as a
      concomitant sign is a rare event. Herein we report a 4-day-old neonate who
      presented with 2 days history of fever and scrotal swelling. Abdominal signs were
      subtle. Scrotum was hugely distended and tense. Workup of the patient revealed
      free intraperitoneal gas with air in the scrotum. At exploration, two
      perforations were found near the greater curvature of stomach and repaired. Post
      operative course was uneventful.

PMID- 22953259
TI  - A giant occipital encephalocele.
AB  - Giant occipital encephaloceles are rare lesions. Because of their enormous size
      they pose a surgical challenge. Herein we report a four months old female baby
      who presented with progressively increasing swelling over the occipital region.
      This swelling was present since birth. Surgery was planned to reduce the size of
      the swelling as well as its contents. The redundant sac was excised and reduced
      sufficiently enough to accommodate the healthy looking brain tissue. In contrast
      to the previous case reports where the neonates had poor prognosis, this infant
      did well postoperatively.

PMID- 22953260
TI  - Immature gastric teratoma: a rare tumour.
AB  - Gastric teratomas are very rare tumours in children. They usually present with a
      palpable mass in the upper abdomen. We report a case of gastric teratoma in one
      and half month old male infant who presented with a palpable mass in abdomen,
      extending from epigastrium to the pelvis. Ultrasound of abdomen revealed a huge
      mass with solid and cystic components. CT scan delineated calcifications in the
      mass. The preoperative diagnosis was a teratoma but not specifically gastric one.
      The mass was excised completely with seromuscular layer of the stomach wall. The
      histopathology confirmed it to be grade-3 immature gastric teratoma. The rarity
      of the origin of teratoma in addition to its immature variety prompted us to
      report the case.

PMID- 22953261
TI  - Intrauterine intussusception causing ileal atresia.
AB  - Intrauterine intussusception (IUI) is the one of the rarest recognized causes of
      jejuno-ileal atresia (JIA). We report on a 15-day old full-term neonate
      presenting with features of intestinal obstruction, wherein on exploration, a
      visible ileo-ileal intussusception resulting in ileal atresia was found. The
      relevant literature has been reviewed.

PMID- 22953262
TI  - Partial avulsion of common bile duct and duodenal perforation in a blunt
      abdominal trauma.
AB  - Complete or partial avulsion of common bile duct is a very rare injury following
      blunt abdominal trauma in children. A 7-year old boy presented to ER following
      blunt abdominal trauma by a moving motorcycle. X ray abdomen revealed free air
      under diaphragm and CT scan showed pancreatic contusion injury. At operation
      anterior wall of common bile duct (CBD) along with a 2mm rim of duodenal tissue
      on either side of anterior wall of CBD were found avulsed from the duodenum. The
      avulsed portion of CBD and duodenum were reanastomosed and a tube cholecystostomy
      performed. The patient had an uneventful recovery.

PMID- 22953263
TI  - Mucinous adenocarcinoma of colon.
AB  - Bleeding per rectum is a common complaint in pediatric age group and mostly
      relates to benign conditions. Underlying colorectal carcinoma is a rare cause and
      carries a poor prognosis. We report two cases of mucinous adenocarcinoma of
      colon, one in a 9 years old male and other in a female of 12 years. The boy
      presented with rectal bleeding and increasing constipation of more than three
      years duration. He had mucinous adenocarcinoma (T3N0MX) of rectosigmoid region
      and underwent local complete resection of the tumor with colostomy. He also
      received postoperative chemotherapy and later underwent colostomy reversal. He is
      tumor free at two years follow up. The girl presented with signs of intestinal
      obstruction and at colonoscopy a stricture found in descending colon. The tumor
      was resected and biopsy reported as poorly differentiated mucinous adenocarcinoma
      with positive mesenteric nodes positive for tumor (T3N2MX). She is on
      chemotherapy.

PMID- 22953264
TI  - Enteroscrotal fistula: a rare complication of incarcerated inguinal hernia.
AB  - Inguinal hernia is a frequent surgical condition encountered of pediatric age
      group. It may get incarcerated and at times strangulated requiring prompt
      intervention. However if lesion is not treated timely a host of complications may
      occur. Enteroscrotal fistula is one such rare complication that may follow such
      discourse. We report a case of 25-days old male neonate who presented with
      enteroscrotal fistula due to incarcerated right inguinal hernia. Patient was
      explored through abdomen and the involved part of ileum was resected and ileo
      ileal anastomosis performed.

PMID- 22953265
TI  - Eventration of diaphragm presenting as small bowel obstruction.

PMID- 22953266
TI  - Conjoined twins: the flip side.

PMID- 22953267
TI  - An interesting case of bishop-koop stoma prolapse.

PMID- 22953268
TI  - Postgraduate training program in pediatric surgery: a way forward.

PMID- 22953269
TI  - Desmoid tumor of the buttock in a preadolescent child.
AB  - Extra-abdominal desmoid tumors are circumscribed but non-capsulated neoplasms of
      differentiated fibrous tissue arising from musculoaponeurotic tissues. They tend
      to be locally infiltrative, resulting in a high rate of local recurrence without
      metastasis, following surgical resection. We report a 9-year-old boy who had a
      large desmoid tumor in his right buttock that was successfully excised.

PMID- 22953270
TI  - Isolated terminal myelocystocele: a rare spinal dysraphism.
AB  - Terminal myelocystocele is a rare spinal dysraphism that present as lumbosacral
      mass. Magnetic resonance imaging (MRI) is the modality of choice for preoperative
      diagnosis. A 2.5 months old female baby presented with lumbosacral skin covered
      mass. There were no associated neurological deficits. MRI of the lesion suggested
      two cysts, one of which was continuous with the central canal of the spinal cord.
      At operation terminal myelocystocele was found with tethering of the spinal cord.
      Untethering of the spinal cord and repair of the myelocystocele performed with
      uneventful recovery.

PMID- 22953271
TI  - Actinomycosis presenting as an abdominal mass in a child.
AB  - Abdominal actinomycosis in childhood period is very rare and a relation to trauma
      is not well established. Herein we report a case that appeared subsequent to
      abdominal trauma. A 17 years old boy presented with left lower quadrant abdominal
      mass and signs of acute abdomen. The symptoms of abdominal discomfort began after
      a fall from height 3 months before admission. There were signs of acute abdomen
      at physical examination. Ultrasound of abdomen demonstrated a mass; CT scan
      findings pointed to a suspicious "internal hernia". An emergency laparotomy was
      performed. During surgery, a mass located over sigmoid colon and infiltrating the
      lateral abdominal wall was found. It was removed en bloc with the adjacent
      omentum. Except for the thickened sigmoid colon, no other pathologies were
      present at laparotomy. The pathology specimen revealed the actinomyces infection.
      The patient was treated with oral penicillin after discharge and the follow-up
      was uneventful. We advocate, keeping the actinomyces infection in mind in cases
      presenting with abdominal mass of unknown origin in childhood period.

PMID- 22953272
TI  - Ischiopagus tripus conjoined twins.
AB  - A conjoined twin is one of the rare congenital defects. Ischiopagus variety is
      even rarer. We present a case of ischiopagus-tripus conjoined twins. They were
      fused at the lower halves of the bodies. One of the twins was apparently normal
      looking, active and pink. The other twin was small, ill looking, sluggish and
      cyanosed. There were two well formed separate lower limbs on one side and a fused
      limb at the other side. The twins had an imperforate anus and two small orifices
      draining urine with incompletely developed external genitalia. Pre-operative
      workup was in progress when the twins passed away.

PMID- 22953273
TI  - Delayed presentation of trichobezoar with small bowel obstruction.
AB  - Small bowel obstruction is a common surgical emergency but trichobezoar as an
      etiology, rarely reported. A seven year old school going female child presented
      with acute intestinal obstruction with a palpable and mobile mass in the abdomen.
      At exploration, a 10 cm long trichobezoar was found in the distal ileum which was
      removed through enterotomy. Postoperative course remained uneventful. Further
      probing revealed that child used to eat her own scalp hairs at the age of 2 years
      and the habit persisted for about 18 months which resulted in alopecia at that
      time. Later on she started showing normal behavior.

PMID- 22953274
TI  - Volvulus of small bowel in a case of simple meconium ileus.
AB  - Meconium ileus is one of important causes of neonatal intestinal obstruction.
      Many patients respond well to nonsurgical management with enemas, however, few
      patients may develop complications in the postnatal period thus requiring urgent
      operation. A 2 day old newborn presented with clinical features of intestinal
      obstruction. There was a suspicion of meconium ileus. Contrast x-ray with
      gastrografin enema was suggestive of unused colon with beaded appearance. Patient
      had to be surgery as repeated enemas did not improve the condition and
      progressive abdominal distension occurred. At exploration twist of the dilated,
      meconium filled loop of small bowel found. De-twisting of the volvulus done and
      Bishop Koop ileostomy fashioned. Patient made an uneventful recovery. Stoma was
      closed six months later.

PMID- 22953275
TI  - Bilious vomiting and volvulus: the eyes cannot see what the mind does not know.

PMID- 22953276
TI  - Recurrent intussusception: management options.

PMID- 22953277
TI  - Where there is no paediatric surgeon!

PMID- 22953278
TI  - Cecal duplication cyst presenting as acute intestinal obstruction in an infant.

PMID- 22953279
TI  - Acute gastric volvulus secondary to malrotation of gut in a child with cerebral
      palsy.
AB  - Acute gastric volvulus secondary to malrotation of gut is a rare surgical
      emergency. We report a case of an eight years old cerebral palsy (CP) child who
      presented to us with sudden upper abdominal distension and non productive
      retching. X-ray abdomen revealed a huge gas shadow on left side of abdomen with
      paucity of distal gas shadows. On exploration organoaxial gastric volvulus with
      gastric ischemia, secondary to malrotation of gut, was found. Volvulus derotated
      and Ladd's procedure was done. Gastropexy and fundoplication was not done due to
      gastric ischemia. Early diagnosis and surgical management can save the patient
      from fatal complications of gastric perforation due to gastric ischemia.

PMID- 22953280
TI  - Lymph nodal infarction simulating acute appendicitis.
AB  - A number of diseases can present as acute right iliac region pain. Lymph node
      infarction, located adjacent to the cecum, mimicking acute appendicitis in a 13
      year-old boy is presented here.

PMID- 22953281
TI  - Metal bezoars causing upper gastrointestinal obstruction in a schizophrenic.
AB  - Metal bezoars are uncommon foreign bodies (FB) in the gastrointestinal tract
      (GIT) and comprised of a wide variety of objects. A 17-year-old schizophrenic
      presented with abdominal pain and distension along with non-bilious vomiting for
      2 weeks. Physical examination revealed dullness to percussion in the epigastrium.
      Plain radiographs revealed objects of metal density contained within a dilated
      stomach. Laparotomy was performed revealing metal objects in stomach. KEYWORDS:
      Metal bezoars, Psychiatric illness, Intestinal obstructionHow to Cite: Siddiqui
      Z. Metal bezoars causing upper gastrointestinal obstruction in a schizophrenic.
      APSP J Case Rep 2011; 2:14.

PMID- 22953282
TI  - Yang-monti continent ileovesicostomy: experience with three cases.
AB  - Mitrofanoff appendicovesicostomy has been the method of choice for dealing with
      urinary incontinence. However, there may be some cases where some alternate
      conduits have to be used. Yang-Monti ileovesicostomy is an alternative to
      Mitrofanoff appendicovesicostomy. Three boys who underwent successful Yang-Monti
      continent ileovesicostomy are reported in this manuscript. In the first case,
      Mitrofanoff procedure was done for traumatic anorectal and urethral disruption
      after attempting ureterosigmoidostomy. Later on, on the request of the patient
      the appendicovesicostomy was excised. The patient presented later with chronic
      renal failure and bilateral hydroureteronephrosis thus an ileovesicostomy was
      fashioned. The patient could not be survived due to chronic renal failure related
      complications. In the second patient with exstrophy of bladder, the ileocecal
      junction along with appendix had to be resected on account of strangulated
      inguinal hernia; later on, an ileovesicostomy was performed for small capacity
      bladder and major degree of vesicoureteric reflux. The third patient with
      exstrophy of bladder, in whom Mitrofanoff procedure had been performed, presented
      with stenosis of the appendicovesicostomy. On re-operation the entire channel had
      disappeared thus necessitated ileovesicostomy. Both of these patients were doing
      well on follow-up.

PMID- 22953283
TI  - True hermaphrodite: a case report.
AB  - True hermaphrodite is one of the rarest variety of disorders of sexual
      differentiation (DSD) and represents only 5% cases of all. A 3-year-old child
      presented with left sided undescended testis and penoscrotal hypospadias. Chordee
      correction was performed 18 months back, elsewhere. At laparotomy Mullerian
      structures were present on left side. On right side testis was normally descended
      into the scrotum.

PMID- 22953284
TI  - Mature gastric teratoma: the mixed exogastric and endogastric variety.
AB  - Gastric teratomas are extremely rare tumors. A 15-day-old neonate presented with
      abdominal mass. Ultrasound of abdomen showed mixed echogenicity lesion. CT scan
      showed a mass with solid and cystic components and internal calcifications. At
      operation a tumor arising from the posterior wall of the stomach found. It was
      exogastric as well as endogastric in location. Biopsy report was suggestive of
      mature teratoma.

PMID- 22953285
TI  - Polysplenia syndrome associated with situs inversus abdominus and type I jejunal
      atresia.

PMID- 22953286
TI  - Aluminum coins in esophagus: a diagnostic challenge.

PMID- 22953287
TI  - Congenital midline cervical skin bridge.

PMID- 22953288
TI  - Spontaneous intravesical knotting of urethral catheter.
AB  - Infant feeding tubes (IFT) have been universally used as urethral catheters in
      neonates and children for several decades. Though generally a safe procedure, it
      may cause significant morbidity if the catheter spontaneously knots inside the
      bladder. We report this complication in three children including a neonate.

PMID- 22953289
TI  - Ewing's Sarcoma in Scapular Region.
AB  - Ewing's sarcoma (ES) primarily affects bones and commonly presents in adolescents
      and young adults. This paper reports a rare case of extra osseous ES of the
      scapular region in a 9 years old girl. She was treated by a multidisciplinary
      approach including surgery, chemotherapy and radiotherapy. She was followed up
      for two years and remained well.

PMID- 22953290
TI  - Reconstructive surgery in a patient with persistent cloaca.
AB  - Cloacal malformations are challenging as to the surgical correction. A case of
      cloacal malformation who underwent reconstructive surgery is being reported. The
      patient had colostomy in the neonatal period and reconstruction was performed at
      the age of 6 year. The surgical management included abdomino-perineal anorecto
      urethro-colo-vaginoplasty. The patient is fully continent of urine and achieved
      fair continence of feces at 9 months of follow up.

PMID- 22953291
TI  - Epigastric heteropagus twin.
AB  - Parasitic twining is a rare type of monozygotic monochorionic monoamniotic
      asymmetrical conjoined twin. We report a case of epigastric heteropagus twin. An
      ultrasound scan showed a defect of 1.5 cm in the epigastrium. CT showed soft
      tissue lobulated mass with fat and air components coming out of the epigastric
      defect. At operation rudimentary alimentary canal with no viscera, was found in
      the parasite. The parasite was easily separated from the host.

PMID- 22953292
TI  - Open safety pin ingestion presenting as incarcerated umbilical hernia.
AB  - Foreign body ingestion is common in children. Sharp foreign bodies are
      potentially harmful and can result various complications. An 8-month-old infant
      presented with incarcerated umbilical hernia. With a suspicion of strangulation,
      operation was performed that revealed a loop of ileum being stuck in the
      umbilical defect. The loop of ileum was freed from the umbilicus which
      demonstrated open ends of safety pin piercing out of bowel lumen. The enterotomy
      followed by removal of safety pin was performed.

PMID- 22953293
TI  - Perforated appendicitis presenting as small bowel obstruction in an infant.

PMID- 22953294
TI  - Omental cake: a radiological diagnostic sign.

PMID- 22953295
TI  - Making home safe for children.

PMID- 22953296
TI  - Peritonitis caused by rupture of infected retroperitoneal teratoma.
AB  - Retroperitoneal teratomas are usually asymptomatic, though there have been
      isolated reports of retroperitoneal teratomas presenting as intra-abdominal
      abscesses and peritonitis in adults. A 7-year-old girl who had presented with
      acute abdomen due to ruptured retroperitoneal teratoma is reported.

PMID- 22953297
TI  - Spontaneous intracerebral haemorrhage in a child.
AB  - Spontaneous intracerebral haemorrhage (SICH) is a rare occurrence in children,
      with different aetiological factors, clinical characteristics and prognosis. A 14
      year male child had sudden onset of headache associated with multiple vomiting.
      Magnetic resonance imaging showed deep seated intracerebral haematoma. Haematoma
      was evacuated successfully and child recovered without deficits. A high index of
      suspicion is necessary for the diagnosis of spontaneous intracerebral haemorrhage
      in children.

PMID- 22953298
TI  - Early recognition of h-type tracheoesophageal fistula.
AB  - Tracheoesophageal fistula (TEF) without associated esophageal atresia (EA) is a
      rare congenital anomaly. Diagnosis in neonatal period is usually not made and
      most of the patients are treated as cases of pneumonia. A case of H-type of
      tracheoesophageal fistula, diagnosed within 24 hours of delivery based upon
      choking and cyanosis on first trial of feed, is being reported. Diagnosis was
      confirmed with contrast esophagram. Through cervical approach fistula was
      repaired and baby had uneventful post operative outcome.

PMID- 22953299
TI  - Popliteal pterygium syndrome: a rare entity.
AB  - The popliteal pterygium syndrome is a congenital malformation that includes
      orofacial, musculoskeletal and genitourinary anomalies. It is a rare autosomal
      dominant disorder. We report one family with popliteal pterygium syndrome
      affecting father and his two daughters, who underwent surgical corrections for
      multiple congenital malformations.

PMID- 22953300
TI  - Mortality in a case of crystal gel ball ingestion: an alert for parents.
AB  - Decorative crystal gel balls are used for decoration purpose. Due to their
      attractive appearance they may be ingested by children. This may result in grave
      complications. A case of decorative crystal ball ingestion is being reported in a
      6 months old infant who presented with sub acute intestinal obstruction and was
      operated. Crystal gel balls were causing obstruction of jejunum. Enterotomy and
      removal of the mass of jelly balls was done with primary closure. The patient was
      re-operated for anastomotic disruption on 6th postoperative day. Baby developed
      septicemia, and succumbed after 2 days of second operation.

PMID- 22953301
TI  - Recurrent desmoid tumor of the buttock in a preadolescent child.

PMID- 22953302
TI  - Abdominal cocoon simulating acute appendicitis.

PMID- 22953303
TI  - A case of fetus in fetu.
AB  - Fetus in fetu is a rare developmental aberration, characterized by encasement of
      partially developed monozygotic, diamniotic, and monochorionic fetus into the
      normally developing host. A 4-month-old boy presented with abdominal mass.
      Radiological investigations gave the suspicion of fetus in fetu. At surgery a
      fetus enclosed in an amnion like membrane at upper retroperitoneal location was
      found and excised. The patient is doing well after the operation.

PMID- 22953304
TI  - Intraperitoneal rupture of hepatic hydatid cyst following blunt abdominal trauma.
AB  - Peritonitis due to rupture of liver hydatid cyst secondary to blunt abdominal
      trauma can present with fatal consequences. Timely diagnosis and appropriate
      surgical management can be life saving. We report a case of ruptured liver
      hydatid cyst in the peritoneal cavity following trauma and its successful
      operative management in a preadolescent previously asymptomatic boy. Importance
      of detailed physical examination and early diagnosis by using appropriate
      radiological investigations is highlighted.

PMID- 22953305
TI  - Congenital median upper lip fistula.
AB  - Congenital median upper lip fistula (MULF) is an extremely rare condition
      resulting from abnormal fusion of embryologic structures. We present a new case
      of congenital medial upper lip fistula located in the midline of the philtrum of
      a 6 year old girl.

PMID- 22953306
TI  - Heterotopic pancreas leading to ileo-ileal intussusception.
AB  - A heterotopic pancreas as the lead point of ileo-ileal intussusception is
      extremely rare. A 12-year-old previously healthy boy, presented to the emergency
      room with the complaint of severe abdominal pain for the last 6-8 hours. A
      preoperative diagnosis of ileo-ileal intussusception was made on ultrasound and
      an emergency exploratory laparotomy was done. At laparotomy an ileo-ileal
      intussusception was found and a polyp noted as a lead point. On histopathology
      this polyp was found to be heterotopic pancreas.

PMID- 22953307
TI  - Bilateral suspected tuberculous empyema thoracis.
AB  - Empyema thoracis is a well known complication following para-pneumonic effusions
      in paediatric age group. Usually it is unilateral but rarely could be bilateral.
      Herein we report a case of bilateral tuberculous empyema thoracis in a 12 years
      old, unvaccinated girl with a positive history of contact with tuberculosis. She
      was managed conservatively with tube thoracostomies and anti-tuberculous drugs.
      Emphasis is on the conservative approach and patience in management of patients
      with bilateral empyema thoracis.

PMID- 22953308
TI  - Biliary atresia associated with polysplenia syndrome, situs inversus abdominus,
      and reverse rotation of intestine.

PMID- 22953309
TI  - Duodenal Duplication Cyst having Ectopic Gastric and Pancreatic Tissues.

PMID- 22953310
TI  - The role of bariatric surgery in the treatment of type 2 diabetes mellitus.
AB  - Medical treatments for patients with type 2 diabetes mellitus and class II and
      above obesity (body mass index greater than 35 kg/m2) are currently limited to
      treatment of diabetes and prevention of its vascular complications. Bariatric
      surgery is by far the most effective treatment not only for weight loss, but also
      for improvement or remission of diabetes. This editorial examines the current
      evidence for the impact of bariatric surgery on weight loss and type 2 diabetes.

PMID- 22953311
TI  - Serum neuron-specific enolase and S100 calcium binding protein B biomarker levels
      do not improve diagnosis of acute stroke.
AB  - BACKGROUND: The high sensitivities and specificities reported for blood
      biomarkers as a supportive test in the diagnosis of acute stroke do not
      correspond with their performance for decision-making in emergency situations.
      METHODS: Seventy-two patients with suspected stroke were recruited: 44 with
      ischaemic stroke, 17 with haemorrhagic stroke and 11 stroke mimics, as well as a
      high-risk control group of 79 individuals. Serum neuron-specific enolase (NSE)
      and S100 calcium binding protein B (S100B) biomarker levels were determined on
      admission, using immunoassay kits. The sensitivities and specificities of NSE and
      S100B for distinguishing acute stroke from stroke mimics and high-risk controls
      were calculated. RESULTS: For cut-off values (NSE <= 14 micrograms per litre and
      S100B <=130 nanograms per litre) the sensitivity was 53% and 55% respectively.
      Specificity was 64 for both versus the stroke mimic group. Specificity was higher
      (79% and 86% respectively) when calculated on the basis of the control group.
      CONCLUSIONS: This study supports the evidence indicating that serum levels of NSE
      and S100B do not improve the diagnosis of acute stroke.

PMID- 22953312
TI  - Blood pressures in subjects for life assurance medical examination and the effect
      of ten minutes recumbent rest.
AB  - BACKGROUND: The prevalence of hypertension in a population is the sum of those
      individuals with a blood pressure (BP) exceeding 140/90 mm Hg plus those with
      normal BP on antihypertensive therapy (this is usually about 20-30% of the
      population). Rest normally reduces BP but the frequency and extent of the fall
      remains unclear. METHODS: This study analysed the results of 1,008 consecutive
      life assurance examinations in which BP was recorded twice, before and after a
      ten minute period of recumbent rest. RESULTS: Two hundred and twelve subjects had
      initial BPs of more than 140/90 mm Hg (21%). When all those receiving
      antihypertensive treatment but with normal BPs were included, this was 26.5%. Of
      the 212 subjects, BP was at a normal level in 147 (69%) after ten minutes at
      rest. CONCLUSION: BP measurement after a ten minute period of standardised rest
      could more accurately identify true hypertension.

PMID- 22953313
TI  - Intravenous fluid use in the acutely unwell adult medical inpatient: improving
      practice through a clinical audit process.
AB  - BACKGROUND: Our Trust developed a clinical guideline to improve the prescribing
      and use of intravenous (IV) fluids based on the British consensus guidelines on
      IV fluid therapy for adult surgical patients. We audited the effect of targeted
      interventions to improve performance against this guideline. METHOD: There were
      53 IV fluid prescription charts in the pre-intervention audit and 48 in the post
      intervention audit. Data was collected on the seven local practice standards
      ('local gold standards') in the clinical guideline; compliance with all of them
      was necessary to meet the IV fluid prescribing bundle of care. RESULTS: The
      proportion of prescriptions which met the IV fluid prescribing bundle of care
      increased (3.8% to 22.9% [p=0.004]) and the legibility of the IV fluid
      prescription increased (28.3% to 56.3% [p=0.004]). CONCLUSION: We have shown that
      the process of prescribing, administering and monitoring IV fluid use can be
      significantly improved through a range of targeted multi-disciplinary
      interventions.

PMID- 22953314
TI  - Radiation dose at CT coronary angiography: how low can we go?
AB  - Computed tomography (CT) coronary angiography is now a widely available and
      reliable test accessible on basic CT platforms that can exclude coronary heart
      disease with confidence. It is fast, cheap and, if properly carried out by
      trained and accredited staff in carefully selected patients, useful information
      can be obtained with acceptably low radiation exposure in some cases.

PMID- 22953315
TI  - Paradoxical coronary artery embolism causing acute myocardial infarction in a
      young woman with factor V Leiden thrombophillia.
AB  - Paradoxical coronary artery embolism is a rare but under-diagnosed cause of acute
      myocardial infarction (AMI) and requires a high level of clinical suspicion to
      make an early diagnosis. We describe the case of a young woman who presented with
      a severe cough and chest pain who was subsequently found to have a paradoxical
      embolus in the right coronary artery. Echocardiography showed a patent foramen
      ovale (PFO) and an atrial septal aneurysm (ASA). The patient was found to be a
      heterozygous carrier of the factor V Leiden mutation that increases the risk for
      venous-thromboembolism. The association between a PFO and an ASA is a risk factor
      for systemic embolisation. This is the first reported case of paradoxical
      coronary artery embolus causing AMI in a non-pregnant patient with factor Leiden
      thrombophilia. Identification of this clinical phenotype is vital as the risk of
      future embolic events can be reduced by anticoagulation and closure of anatomical
      cardiac defects.

PMID- 22953316
TI  - Anti-Ri-associated paraneoplastic cerebellar and brainstem degenerative syndrome.
AB  - We present the case of a female patient with a subacute paraneoplastic brainstem
      neurological syndrome associated with breast cancer and the development of anti
      Ri antineuronal antibodies (ANNAs). It is an important syndrome to identify
      because of the need for urgent investigation and management to reduce progressive
      and irreversible neurological deterioration and to recognise the associated risks
      of bulbar and central respiratory failure. Diagnosis can be confounded if the
      anticipated normality of imaging and cerebrospinal fluid (CSF) studies is not
      appreciated. Positive antineuronal screening can provide rapid support for a
      paraneoplastic aetiology. Urgent and extensive investigation to identify the
      underlying tumour is imperative since neurological outcome is dependent on the
      rapidity of commencement and efficacy of tumour therapy. We discuss the symptoms,
      pathophysiology, diagnosis, treatment and prognosis of paraneoplastic
      neurological syndromes.

PMID- 22953317
TI  - Apparent oliguria following urological surgery.
AB  - Oliguria is a common feature of acute kidney injury (AKI), but should be
      interpreted in the context of other biochemical markers when diagnosing and
      monitoring AKI or considering the need for renal support. We report an unusual
      case of apparent severe oliguria arising as a result of complex urological
      pathology and discuss how an understanding of creatinine kinetics raised
      suspicions of an alternative diagnosis. We discuss the problems caused by an over
      reliance on urine output or serum creatinine alone when diagnosing and staging
      AKI and highlight the need for a more holistic approach.

PMID- 22953318
TI  - Treating type 2 diabetes in youth: a depressing picture.
AB  - There is an increase in type 2 diabetes (T2D) in children, yet little evidence to
      guide management. The TODAY study aimed to assess the impact of three treatment
      interventions in this demographic group.1 In this study 927 children were
      converted from their current medication to metformin monotherapy. This run-in
      phase proceeded to randomisation if an HbA1c <8% (64 millimoles per mole
      [mmol/mol]) was achieved with adherence to medication >80% for at least six
      weeks. The randomisation cohort consisted of 699 children, aged between 10 and 17
      years with T2D diagnosed within the past two years and a body mass index (BMI)
      >85th percentile. The ethnicity split was 41% Hispanic, 31.5% non-Hispanic Black,
      and 20% non-Hispanic White. The children were randomly assigned to stay on
      metformin alone, to have rosiglitazone added to their regime, or to continue on
      metformin and undergo a family based behavioural weight loss programme. This
      consisted of weekly visits for the first six months, then biweekly for six
      months, then bimonthly for the remainder of the study. The primary endpoint was
      either an HbA1c >8% for more than six months, or sustained insulin treatment for
      more than three months. Treatment failure was observed in 45.6% of children; 50%
      by 11.5 months after randomisation. Treatment failure was seen less in those with
      rosiglitazone added (38.6%) compared to those who stayed on metformin alone
      (51.7%, p=0.006). Intensive lifestyle intervention had an intermediate result
      (46.6% failure) but this did not differ significantly from those taking metformin
      alone. The authors conclude that whatever the intervention, progression of
      diabetes is rapid in this age group and that multiple oral treatments or insulin
      will be required within a few years for the majority of this group.

PMID- 22953319
TI  - Current controversy: Triage of acute onset chest pain: now a biochemical rule-out
      test?
AB  - The management of coronary disease has moved forward with the application of more
      sensitive blood biomarkers for early detection alongside more structured symptom
      assessment, examination and serial ECG measures. However every episode of
      exertional chest pain isn't symptomatic coronary disease and given massive public
      awareness campaigns we now face a different management issue with undiagnosed
      chest pain sent as a 'rule-out' activity. These urgent referrals are often
      justified based on the management of the minority with unstable coronary disease
      without preliminary medical review or examination. Avoiding delay which is
      valuable in coronary patients may be irrelevant to the majority. The overall
      effectiveness of this pathway is unclear where the patient does not have coronary
      disease but also where superficial interpretation can be misleading through non
      specificity. Do biomarker assays become the answer to every chest pain patient
      and has the basic assessment of the individual patient and a prior probability of
      disease no role to play? Does this activity represent a burden or an irrelevant
      dead end for non-coronary patients? We have asked for comment from two leading
      authorities on the evolving role and application of cardiac biomarker
      technologies in managing this considerable and common clinical dilemma.

PMID- 22953320
TI  - Public health aspects of tuberculosis.
AB  - This article covers public health aspects of the investigation and management of
      people who are infected with tuberculosis (TB). It contains a brief overview of
      the recent epidemiology of TB in Scotland, focusing on changes in Scottish TB
      incidence and describing some epidemiological associations. We then describe the
      initial public health assessment of those with suspected TB and responses that
      should be initiated. It does not address issues relating to the clinical
      treatment of patients with TB.

PMID- 22953321
TI  - Pharmacogenetics: transforming clinical medicine.
AB  - Pharmacogenetics, the study of genetic variation relevant to drug metabolism, is
      a rapidly evolving area of medicine. This brief review will consider some of the
      recent advances where inherited genetic variants have been associated with either
      drug efficacy or toxicity. Examples of where pharmacogenetic testing has been
      adopted into clinical practice will be provided as well as a look at its likely
      development over the next decade. Finally, the large increase in genetic testing
      of tumour tissue samples to predict response to molecularly targeted treatments
      in cancer will be considered.

PMID- 22953322
TI  - Observing the NICEties of hypertension management.
AB  - National Institute for Health and Clinical Excellence guidance for the clinical
      management of hypertension, published last year, proposes a step change in UK
      clinical practice.1 Although broadly helpful, there are some concerns about its
      implementation. Ambulatory blood pressure monitoring for diagnosis of
      hypertension, though logical, will place an additional financial burden on
      primary care at a time of austerity. Home blood pressure measurement may be a
      more practical option. Previous guidance recommended the used of thiazide
      diuretics as a first-line treatment option.2 Five years later, the new guidelines
      propose a major change, with an initial emphasis on the use of calcium channel
      blockers and angiotensin converting enzyme inhibitors/angiotensin receptor
      blockers, moving the use of thiazide-like diuretics to a third-line option. In
      addition, bendroflumethiazide, the mainstay of treatment in the UK over many
      years, has been replaced with chlortalidone, the starting doses of which are not
      readily available in this country. Cost-effectiveness analysis and a presumed
      risk of metabolic disorders has guided the rationale for these changes to the
      therapeutic algorithm, however this may not be robust. Importantly, unless there
      are special circumstances, reducing the blood pressure in hypertensive patients
      is more important than the means used to lower it. In future, it will be
      important to 'personalise' treatment more effectively and base management on
      lifetime risk.

PMID- 22953323
TI  - Dr James Barry (1789-1865): the Edinburgh years.
AB  - Dr James Barry, a surgeon in the British Army from 1813 until his retirement in
      1859, became famous after his death following the revelation that he was in fact
      a woman who had masqueraded as a man for no less than 56 years. This paper
      reviews Margaret Bulkley's student years at the University of Edinburgh from the
      time of her adoption of the identity of the youth calling himself James Barry.
      The deception was perpetrated in order to obtain a medical degree and the three
      year MD curriculum was completed without discovery. Few facts are known about
      these years (1809-1812) and the work of Lisa Rosner has been invaluable as a
      source of prosopographical information to apply to our knowledge of James Barry's
      experiences during his time at Edinburgh. Contemporary letters and an Army
      document also assist in developing this unique and extraordinary story, revealing
      much that was previously unknown as well as some data, which in earlier work were
      incorrectly reported.

PMID- 22953324
TI  - The most deadly disease of asylumdom: general paralysis of the insane and
      Scottish psychiatry, c.1840-1940.
AB  - General paralysis of the insane (GPI) was one of the most devastating diseases
      observed in British psychiatry during the century after 1840, in terms of the
      high number and type of patients diagnosed, the severity of its symptoms and,
      above all, its utterly hopeless prognosis. With particular reference to the
      physicians and patients of the Royal Edinburgh Asylum, this article explores the
      diagnostic process and the social and medical significance of the 'death
      sentence' that accompanied the GPI diagnosis.

PMID- 22953325
TI  - Sir Charles Locock and potassium bromide.
AB  - On 12 May 1857, Edward Sieveking read a paper on epilepsy to the Royal Medical
      and Chirurgical Society in London. During the discussion that followed Sir
      Charles Locock, obstetrician to Queen Victoria, was reported to have commented
      that during the past 14 months he had used potassium bromide to successfully stop
      epileptic seizures in all but one of 14 or 15 women with 'hysterical' or
      catamenial epilepsy. This report of Locock's comment has generally given him
      credit for introducing the first reasonably effective antiepileptic drug into
      medical practice. However examination of the original reports raises questions as
      to how soundly based the accounts of Locock's comments were. Subsequently, others
      using the drug to treat epilepsy failed to obtain the degree of benefit that the
      reports of Locock's comments would have led them to expect. The drug might not
      have come into more widespread use as a result, had not Samuel Wilks provided
      good, independent evidence for the drug's antiepileptic efficacy in 1861.

PMID- 22953326
TI  - Andreae Vesalii Bruxellensis Icones anatomicae. Part 2.

PMID- 22953327
TI  - History.

PMID- 22953328
TI  - History.

PMID- 22953329
TI  - The Richmonds in Khartoum.

PMID- 22953330
TI  - Bone marrow oxalosis.

PMID- 22953331
TI  - The flickering genes of the last mammoths.
AB  - Woolly mammoths, Mammuthus primigenius, are arguably the most iconic of the
      extinct Pleistocene megafauna, and an abundance of large permafrost-embedded bone
      and ivory material (Fig. 1) means they were also among the first to yield
      credible DNA sequences (Hagelberg et al. 1994; Hoss et al. 1994). Despite mammoth
      remains being numerous throughout northern Eurasia and North America, both the
      earliest and most recent fossils are found in northeast Siberia, with the last
      known population being confined to Wrangel Island in the Arctic Ocean from around
      10,000 years ago until their extinction around 4,000 years ago. The extent to
      which these Holocene mammoths were descended from the Pleistocene populations of
      Wrangel Island and the demographic nature of their terminal decline have, until
      now, remained something of a mystery. In this issue of Molecular Ecology, Nystrom
      et al. (2012) report the first use of autosomal variation to track the decline of
      the last mammoths and, in doing so, take a significant step towards resolving
      these questions. The authors genotyped four microsatellite loci in 59 Pleistocene
      and Holocene mammoths from Wrangel Island and Chukotka in mainland northeastern
      Siberia and showed that while the Pleistocene-to-Holocene transition is
      associated with a significant reduction in genetic diversity, subsequent levels
      of variation remain constant until extinction. Such a pattern is somewhat
      surprising as it indicates that while the last mammoths were confined to only a
      few Arctic islands, their final extinction on Wrangel Island was not a gradual
      process resulting from loss of genetic diversity/inbreeding. Instead, it seems
      they maintained a viable effective population size of around 500 until near their
      presumably rapid extinction. While the ultimate agent of mammoth extinction
      remains unknown, the work of Nystrom et al. (2012). suggests that we should be
      looking for something sudden, like a rapid change in climate/ecology or perhaps
      the arrival of humans.

PMID- 22953332
TI  - Ecological proteomics: finding molecular markers that matter.
AB  - It is becoming increasingly clear that local adaptation can occur even in the
      face of high gene flow and limited overall genomic differentiation among
      populations (reviewed by Nosil et al. 2009). Thus, one important task for
      molecular ecologists is to sift through genomic data to identify the genes that
      matter for local adaptation (Hoffmann & Willi 2008; Stapley et al. 2010). Recent
      advances in high-throughput molecular technologies have facilitated this search,
      and a variety of approaches can be applied, including those grounded in
      population genetics [e.g. outlier analysis (Pavlidis et al. 2008)], classical and
      quantitative genetics [e.g. quantitative trait locus analysis (MacKay et al.
      2009)], and cellular and molecular biology [e.g. transcriptomics (Larsen et al.
      2011)]. However, applying these approaches in nonmodel organisms that lack
      extensive genetic and genomic resources has been a formidable challenge. In this
      issue, Papakostas et al. (2012). demonstrate how one such approach - high
      throughput label-free proteomics (reviewed by Gstaiger & Aebersold 2009; Domon &
      Aebersold 2010) - can be applied to detect genes that may be involved in local
      adaptation in a species with limited genomic resources. Using this approach, they
      identified genes that may be implicated in local adaptation to salinity in
      European whitefish (Coregonus lavaretus L.) and provide insight into the
      mechanisms by which fish cope with changes in this critically important
      environmental parameter.

PMID- 22953333
TI  - [Dupuytren's disease - the story of an eponym].
AB  - December 5, 1831, baron Guillaume Dupuytren presents at the surgical clinics of
      the Hotel-Dieu of Paris a report upon "an entirely new subject, with a new theory
      and a new method of treatment for a disease generally regarded as incurable". The
      patient presented had a permanent contraction of the ring finger and adjacent
      fingers of both hands, which appeared spontaneously without any injury or
      previous illness. Dupuytren explains he had the opportunity to dissect the hand
      of a man who died after having had a contraction of the fingers for many years.
      He defines the cause of the contraction to be the palmar fascia. He describes the
      operative treatment: aponeurotomy by a transverse incision. "Probably many
      surgeons (Cline 1808, Astley Cooper 1822) were aware of the palmar aponeurosis
      producing this condition before Dupuytren's lecture". "Thoroughness of his
      demonstration, the brilliance of the presentation and the supremacy of his
      surgical authority combined to link permanently the name of Dupuytren with this
      hand deformity" (J. Hueston).

PMID- 22953334
TI  - [Cystic lymphangioma of the scrotum].
AB  - The cystic lymphangioma is a relatively frequent affection. The scrotum is the
      least common sites. It is a benign tumor discovered during an examination or in a
      fortuitous way. The diagnosis is done with ultrasonography and the treatment of
      the limited and circumscribed cases, is a surgical excision. We reported the case
      of a child of 2 years old which was presented to the surgery emergency for the
      scrotum traumatism. The clinical and paraclinical exams founded a cystic mass.
      After mass excision, histopathology founded a cystic lymphangioma.

PMID- 22953335
TI  - [Epiphyseal growth fractures: epidemiology and treatment. Retrospective report of
      44 cases].
AB  - OBJECTIVE: To value the frequency of epiphyseal growth fracture and to take out
      the therapeutic aspects of the epiphyseal growth fracture and to value the
      results for un good management. PATIENTS AND METHOD: It is about a retrospective
      study carrying on 44 children aged of less than 15 years hospitalized and treated
      in the pediatric surgery department or the Tokoin teaching hospital (Lome) from
      1st January 2002 to 31st December 2006. RESULTS: The prevalence of epiphyseal
      growth fracture was of 3.6% with a masculine predominance(59.1%). The middle age
      was of 9.8 }3.2 years.The type 2 lesions of Salter and Harris classification
      represented 44%. The accidents of game were the main suppliers (41 %) with
      affluence in April and August. The orthopedic treatment was applied in 64.4% of
      case. With a middle receding of 2 years, 4 patients had presented some
      afterrnaths. CONCLUSION: Epiphyseal growth fracture has a relatively frequency.
      The diagnostic trap of the epiphyseal growth fracture is numerous and is
      sometimes the origin of the therapeutic mistake. Their treatment must be well
      codified to avoid some long-term afterrnaths.

PMID- 22953336
TI  - [Anticoagulation therapy in developing countries].

PMID- 22953337
TI  - [Bilharziasis and urinary lithiasis: a study of 23 cases at the Gabriel Toure
      Hospital].
AB  - AIMS: Describe the clinical and therapeutic aspects of urinary stone on
      bilharziosis in the teaching hospital Gabriel Toure. METHOD: It was about a
      prospective study done from January 1st to December 31, 2007 on all patients
      presenting a urinary stone with history of bilharziosis treated in the service of
      urology at the teaching hospital Gabriel Toure. Lost patients during the study
      were not included. RESULTS: We brought together 23 cases of urinary stone on
      history of urinary bilharziosis. The mean age of our patients was 31 years with
      extreme of 10 and 64 years. Sex-ratio was 22 for men. Renal colic was the most
      frequent motive of consultation (30.4%). Fiver has been detected in 56.5% of
      cases.Stone has a renal localisation in 10 patients (43.5%), ureteral in 9
      patients (39.1%) and vesical in 4(17.4%). Urine analysis has found following
      germs: Schistosoma haematobium (4 cases), positive cocci gram (3 cases),
      Enterococcus faecalis (1 case) and negative cocci gram (1 case). Moderate renal
      insufficiency has been detected in 4 patients (17.4%). Treatment has been
      surgical in 21 patients(91.3%). Nephrolithotomy was done in 7 patients (33.3%),
      ureterolithotomy in 7 others, cystolithotomyin 3 patients (14.3%), nephrectomy in
      2 patients (9.5%), uretero-vesical reimplantation in 2 others. CONCLUSION: The
      assessment of bilharziosis may decrease the frequency and prevent numerous and
      disastrous complications of urinary bilharziosis.

PMID- 22953338
TI  - [Non-resecable gastric cancers at the department of general surgery at CHU
      Gabriel TOURE Bamako].
AB  - Our objectives were to determine the frequency of non-resecable gastric cancers,
      to analyse its clinical, and therapeutic aspects, and to assess patients follow
      up. METHOD: Our retrospective study has been from 1st January 2008 to 31st
      December 2009. It included all patients operated or not having non-resecable
      gastric cancers at general surgery at CHU Gabriel TOURE RESULTS: We have recorded
      305 cases of advanced gastric cancers, accounting for 71.4% of gastric cancers
      (n=425), 47.8% of digestive cancers (n=766) and 2.2% of hospitalisations. The sex
      ratio was 1.6 in men favour; the average age was 57 } 12 with extremes of 25 and
      90. The average evolution delay was 15.5 months with extremes of 5 and 7, and
      standard deviation 19.2. 14 patients have been admitted in an emergency context.
      (8 cases of gastric perforation related peritonitis, 6 cases d'haematemesis). The
      main found signs were: epigastric tumours 187 (61.3%) cases, lower limbs oedema
      105 (34.4%) cases, ascitis 105(34.4%) cases, hepatomegaly 68(22.3%),
      lymphadenopathy ? ganglions de Troisier ?21(7%), ? ecailles de Brumer ? (=
      Brumer's scales) from rectal touch 17(6%) cases More than half of patients have
      been classified ASA 4.105(34.4%) ASA 5, and 74(24.2%) ASA . The tumour location
      was antrum in 260(85.2%) cases Cardiac orifice in 17(5.5%) cases, fundus i n
      11(3.6%), the gastric linitis in 17(5,5%) cases. The imaging has found the
      ascitis in 119(39%) cases, the hepatic metastases in 54(17.7%) cases, pulmonary
      in 36(19%) cases, pancreatic 5(1.6%) cases, splenic in 4(1.3%), and ovarian in
      3(1%) cases 105(34.4%) patients had no surgery, 4(1.3%) had chemotherapy, and
      200(65 %) had surgery. The mortality rate was at 16.5% and the one year survival
      at 15.5%.

PMID- 22953339
TI  - [Eye involvement of drug eruptions: report of 10 cases].

PMID- 22953340
TI  - Less than expected. With projections that the Supreme Court's ACA ruling means
      fewer will be insured, providers are scrambling to find out how they'll fare and
      sending PAC cash to those who can help.
AB  - The CBO has come up with its numbers on how the ACA ruling will affect hospitals.
      And providers are worried. "When the law was passed, the idea was there would be
      less DSH money, but more people will be covered, and we won't need as much DSH
      money," says Dr. Bruce Siegel, left, of the National Association of Public
      Hospitals and Health Systems. "Now, half of that is gone-the coverage is expected
      to be less".

PMID- 22953341
TI  - Medicare cuts loom...but some healthcare leaders in Congress in dark.

PMID- 22953342
TI  - Living in uncertain times. Some simple lessons from our nation's farmers and
      healthcare providers.

PMID- 22953343
TI  - Subtracting add-ons. Expiration of Medicare 'extenders' pushing some rural
      hospitals to the edge.

PMID- 22953344
TI  - Hospital CEO turnover by state. Ranked by highest chief executive turnover
      percentages in 2011.

PMID- 22953345
TI  - Made-to-order mess. States could seek customized Medicaid solutions in wake of
      ACA ruling.

PMID- 22953346
TI  - A model approach. Grants aim to bolster care quality, slash costs.

PMID- 22953347
TI  - Tune it out. Healthcare policy will surely suffer in the campaign ad deluge.

PMID- 22953348
TI  - 25 largest post-acute-care companies. Ranked by 2011 net revenue, based on Modern
      Healthdcare's 2012 post-acute-care surevey.

PMID- 22953349
TI  - For what it's worth. Executives' earnings vary, but not necessarily based on
      organizations' value.

PMID- 22953350
TI  - Largest national healthcare associations. Organizations ranked by 2010 revenue,
      based on Modern healthcare's review of IRS form 990 filings.

PMID- 22953363
TI  - Advances in ventricular assist devices improve care of heart failure patients. 
      VADs help improve the lives of patients waiting for heart transplants, as well as
      those who are not good candidates for transplantation.

PMID- 22953364
TI  - Aortic dissection poses life-threatening emergency. A weakened aortic wall can be
      repaired if diagnosed in time.

PMID- 22953365
TI  - Sleep apnea and snoring put your heart health at risk.  Research shows sleep
      apnea contributes to a buildup of non-calcified plaque in the arteries.

PMID- 22953366
TI  - Stroke prevention guidelines look at carotid artery treatments.  Updated
      guidelines also focus on cholesterol and blood pressure control.

PMID- 22953367
TI  - Proceedings from "Clinical Dermatology Updates - Atopic Dermatitis", 3-4 March,
      2012, Mumbai .

PMID- 22953368
TI  - Cystoscopy.

PMID- 22953369
TI  - Peripheral and visceral arteriography.

PMID- 22953370
TI  - Total knee replacement.

PMID- 22953371
TI  - Mohs micrographic surgery.

PMID- 22953372
TI  - Pulmonary artery catheterization.

PMID- 22953373
TI  - Recurrent Candida parapsilosis infective endocarditis aortic root replacement.

PMID- 22953374
TI  - Amiodarone-induced facial pigmentation.

PMID- 22953376
TI  - Abstracts of Breast Cancer Research 2012. May 18, 2012. London, United Kingdom.

PMID- 22953375
TI  - Abstracts of the 9th Pan African Society of Cardiology and the Annual Nigerian
      Cardiac Society Congress. September 26-30, 2009. Abuja, Nigeria.

PMID- 22953377
TI  - Retraction of "Does patient assessment of the quality of the primary care they
      receive predict subsequent outcomes? An Oklahoma Physicians Resource/Research
      Network (OKPRN) study".

PMID- 22953378
TI  - [Psychosomatic medicine and psychotherapy - more current than ever].

PMID- 22953379
TI  - Evaluation of certain veterinary drug residues in food.
AB  - This report represents the conclusions of a Joint FAO/WHO Expert Committee
      convened to evaluate the safety of residues of certain veterinary drugs in food
      and to recommend maximum levels for such residues in food. The first part of the
      report considers general principles regarding the evaluation of residues of
      veterinary drugs within the terms of reference of the Joint FAO/WHO Expert
      Committee on Food Additives (JECFA), including comments on documents under
      elaboration for the Codex Committee on Residues of Veterinary Drugs in Foods
      (CCRVDF), information on registration/approval status of veterinary drugs,
      extrapolation of maximum residue limits (MRLs), dietary exposure assessment
      methodologies, the decision-tree approach to the evaluation of residues of
      veterinary drugs and guidance for JECFA experts. Summaries follow of the
      Committee's evaluations of toxicological and residue data on a variety of
      veterinary drugs: two antimicrobial agents (amoxicillin, apramycin), four
      anthelminthics (derquantel, ivermectin, monepantel, triclabendazole) and two
      antimicrobial agents and production aids (monensin and narasin). Annexed to the
      report is a summary of the Committee's recommendations on these drugs, including
      acceptable daily intakes (ADIs) and proposed MRLs.

PMID- 22953380
TI  - WHO Study Group on Tobacco Product Regulation. Report on the scientific basic of
      tobacco product regulation: fourth report of a WHO study group.
AB  - This report presents the conclusions reached and recommendations made by the
      members of the WHO Study Group on Tobacco Product Regulation at its sixth
      meeting, during which it reviewed two background papers specially commissioned
      for the meeting and which dealt, respectively, with the following two themes. (1)
      toxic elements in tobacco and in cigarette smoke (2) the basis for a regulatory
      framework to reduce the dependence potential of tobacco products The Study
      Group's recommendations in relation to each theme are set out at the end of the
      section dealing with that theme; its overall recommendations are summarized in
      section 4.

PMID- 22953382
TI  - Other people's lives: reflections on medicine, ethics, and euthanasia.

PMID- 22953381
TI  - Woman's Right to Know Act: a legislative history.
AB  - This article provides a comprehensive legislative history of North Carolina's
      Woman's Right to Know Act of 2011. The Act requires informed consent and a
      mandatory twenty-four hour waiting period for abortion, thus protecting a woman's
      right to make an informed choice. Informed consent provisions and mandatory
      waiting periods give individuals making decisions the information and time
      necessary to make informed choices. The Act further provides that an ultrasound
      be performed and explained no less than four hours and no more than seventy-two
      hours before the abortion. The article first provides a brief overview of sources
      of legislative history recognized in North Carolina. It then details the history
      of the Woman's Right to Know Act, from the first informed consent bill introduced
      in 1981, to the passage of the 201l law, and to the federal court case that
      followed. Finally it provides specific objections that were raised against the
      bill and responses to each. Legislators considering similar legislation need to
      be aware of the opposition they inevitably will encounter when passing such a
      bill. The author expects that this history and the ultimate success of North
      Carolina will encourage other states' legislators and lawyers and give them the
      tools to make their case effectively.

PMID- 22953383
TI  - Leadership lessons from great corporate leaders: the results of a 30-year study.

PMID- 22953384
TI  - 36 traits of great leaders.

PMID- 22953385
TI  - Top CEOs share the secrets to operating a successful hospice, private duty, and
      comprehensive home care company.

PMID- 22953386
TI  - A tribute to the Visiting Nurse Association of Greater Philadelphia.

PMID- 22953387
TI  - Connecting with the heart: a case history. The BAYADA Way project ten years
      later.

PMID- 22953388
TI  - My Alzheimer's, God forbid.

PMID- 22953389
TI  - Sundowning in the Alzheimer's patient.

PMID- 22953390
TI  - The importance of identifying malnutrition for improved outcomes.

PMID- 22953391
TI  - The customer is always (right!) the customer.

PMID- 22953392
TI  - In defense of compassionate capitalism.

PMID- 22953393
TI  - Careless talk can have serious consequences.

PMID- 22953394
TI  - University partnership seeks to promote a culture of innovation.

PMID- 22953395
TI  - Atos work assessments are 'morally wrong' and deny rightful benefits.

PMID- 22953396
TI  - Report suggests healthcare staff assume BME patients are straight.

PMID- 22953397
TI  - Stricter recruitment aims to improve care at mid staffs trust.

PMID- 22953398
TI  - 'It is about being highly visible to your patients at least every hour'.

PMID- 22953399
TI  - A powerful mechanism for change.

PMID- 22953400
TI  - Battle for excellence.
AB  - Former army nurse Claire Stephens has launched a charity to improve the care that
      wounded military personnel receive from the NHS. Many soldiers have complex
      wounds that will require treatment for many years. Woundcare4Heroes aims to
      provide specialist care to veterans and support NHS staff with training.

PMID- 22953401
TI  - A dose of empathy.
AB  - The use of antipsychotic medication treatment of people with dementia in England
      has halved over the past three years. This success reflects improvements in care
      but more can be done to meet individuals' needs and avoid the triggers to
      'challenging' behaviour.

PMID- 22953402
TI  - Shared experience.
AB  - An innovative parenting programme in Luton is supporting vulnerable families by
      helping mothers to interact positively with their children and recognise the past
      experiences that have influenced their parenting styles. Nurses who facilitate
      the programme's group sessions are required to share personal experiences with
      the other participants and reflect on their own parenting.

PMID- 22953403
TI  - Cardiopulmonary resuscitation in end of life care.
AB  - This article discusses ethical, legal and professional issues surrounding 'do not
      attempt cardiopulmonary resuscitation' (DNACPR) decisions in end of life care.
      The principles outlined throughout this article are applicable in any care
      setting. It explains what a DNACPR decision is, its relevance to clinical
      practice, and provides guidance on decision making and its implementation. The
      article also discusses the ethical considerations when discussing DNACPR
      decisions with patients and families, as well as the legal issues surrounding
      advance decisions to refuse treatment. Case studies are used to link theory to
      practice.

PMID- 22953404
TI  - Myeloproliferative neoplasms: diagnosis, management and treatment.
AB  - This article provides an overview of myeloproliferative neoplasms for nurses who
      do not specialise in haematology. Diagnosis, management and treatment of patients
      with these conditions is discussed, as well as long-term nursing implications.

PMID- 22953405
TI  - Raising awareness of dengue fever.
AB  - Dengue fever is a disease of increasing relevance to international travellers.
      Transmitted by the bite of infected mosquitoes, it is recognised as the most
      common arthropod-borne infection worldwide. With no vaccine available to prevent
      infection, accurate pre-travel advice and post-travel follow up is necessary.
      Healthcare professionals who provide advice to overseas travellers need to have a
      comprehensive understanding of the disease.

PMID- 22953406
TI  - Preventing falls.

PMID- 22953407
TI  - A platform for care.

PMID- 22953408
TI  - Facing the future.

PMID- 22953409
TI  - Keep education relevant.

PMID- 22953410
TI  - Humanity and dignity for all.

PMID- 22953411
TI  - A fresh perspective.

PMID- 22953412
TI  - A role defined by local need.

PMID- 22953414
TI  - Vital signs are vital for a reason.

PMID- 22953413
TI  - Put it down on paper.

PMID- 22953415
TI  - First union says "no" to AFC cuts.

PMID- 22953416
TI  - "Learning disability services must be reshaped and localised".

PMID- 22953417
TI  - "Nursing is a bit like the Olympics--it gives us something special".

PMID- 22953418
TI  - "Standardise intravenous line care to reduce infection risk".

PMID- 22953419
TI  - Care of peripheral venous cannula sites.
AB  - Peripheral venous catheters are commonly used in hospitals to deliver intravenous
      therapy. They are associated with a range of complications that can be damaging
      to patients' health and increase healthcare costs. In order to minimise the risk
      of these complications, thorough patient assessment and careful catheter
      management are essential.

PMID- 22953420
TI  - Symptom "accommodation" in patients with COPD.
AB  - Patients with COPD often learn to "accommodate" their symptoms, which makes it
      difficult for health professionals to assess the impact of the condition on their
      daily lives. This article explores the concept of accommodating COPD symptoms and
      gives advice to encourage optimal treatment.

PMID- 22953421
TI  - Quality indicators to measure end-of-life care.
AB  - This article gives examples of how to use quality indicators to demonstrate and
      improve effectiveness in supporting people with their end-of-life care needs.

PMID- 22953422
TI  - Benefits of a peripatetic port mentor.
AB  - Mentors play a crucial role in helping student nurses to develop their knowledge
      and skills, yet the quality of mentoring can be inconsistent. Peripatetic mentor
      support could promote consistency in placement learning by helping to bridge some
      gaps between clinical staff and universities. This article describes the
      introduction of a new role--peripatetic support mentor--and its benefits.

PMID- 22953423
TI  - Olympic nurses go the distance.

PMID- 22953424
TI  - How to make a visible difference to culture.

PMID- 22953425
TI  - [The educational system of today and health personnel of tomorrow].

PMID- 22953426
TI  - [Medical and academic leadership is required for IT support for drugs. The
      principles of good decision support practice (GDSP) should be followed].

PMID- 22953427
TI  - [29-year-old man treated with splenectomy died of pneumococcal sepsis. Important
      that pneumococcal vaccination of splenectomised is not forgotten].

PMID- 22953428
TI  - [Life-threatening infection in splenectomised patients is preventable. But this
      requires better vaccination routines, education and antibiotic prophylaxis].

PMID- 22953429
TI  - [Anticoagulant treatment audited in the south of Sweden. A well functioning
      practice--which can improve even more].

PMID- 22953430
TI  - [Osteomalacia due to phosphate deficiency caused by a tumor. Focus on FGF23 in
      physiology and clinic].

PMID- 22953431
TI  - [Drugs against schizophrenia: SBU fails to sort things out].

PMID- 22953432
TI  - [In combat with psychiatry and law: Knut Hamsun's art and diagnosis].

PMID- 22953433
TI  - The effect of education on nurses' assessments in an epilepsy monitoring unit.
AB  - BACKGROUND: There are few data about the quality of nursing care on an epilepsy
      monitoring unit. This study evaluated the impact of an educational program on the
      quality of care provided by nurses in an epilepsy monitoring unit (EMU) using an
      investigator-developed assessment tool. OBJECTIVES: There were two objectives for
      this study. The first objective was to measure nurses' assessments of patients on
      the EMU in a quantifiable form. The second objective was to evaluate the
      effectiveness of an educational program on the scores of the Nursing Assessment
      Rating Scale. SUBJECTS: Twenty-five nurses working in the EMU participated in the
      study. RESULTS: Nurses' assessments were quantified using a criterion-based
      rating scale with seven primary quality indicators. Prior to the educational
      program, the mean scores on the rating scale were 14.5 points (SD 2.1). Post
      education, there was a statistical difference in scores (mean 16, SD 1.6, p<.01).
      CONCLUSIONS: The Nurse Assessment Rating Scale enabled the researchers to
      transform a qualitative measure of assessment into a quantitative indicator that
      could be compared pre- and post-education. Second, data indicated that the
      education significantly improved the assessment scores. With education, original
      protocols were reinforced and assessments became more consistent resulting in
      improved scores. Third, using a multimodal education format targeted aspects of
      performance such as respect and compassion.

PMID- 22953435
TI  - Epidemiology and prevention of combat-related post-traumatic stress in
      OEF/OIF/OND service members.
AB  - This article summarizes information about the prevalence of post-traumatic stress
      disorder (PTSD) in military personnel and Veterans who have served in the Iraq
      and Afghanistan conflicts as well as the disorder's impact and efforts to prevent
      it in this population. We examine prevalence in light of epidemiologic methods
      and discuss associated outcomes, etiology, and factors affecting risk for PTSD.
      Prevention strategies are presented both in terms of individual-level
      interventions and operational strategies designed to mitigate the development of
      PTSD. Our findings indicate that while research into the prevalence and
      consequences of PTSD in the Iraq and Afghanistan cohort has been significant,
      relatively little is known about the effectiveness of approaches designed to
      prevent it.

PMID- 22953434
TI  - Experience and satisfaction of staff working in a seizure monitoring unit.
AB  - The purpose of this study was to investigate staff experience and satisfaction in
      the seizure monitoring unit (SMU) of a large health region serving a population
      of 1.4 million. A staff satisfaction questionnaire was administered yearly
      between 2007 and 2010 with an average response rate of 58.4%. The majority of
      staff perceived the SMU to be a positive workplace. Strengths of the SMU were
      interdisciplinary teamwork and patient-centred care. Satisfaction with
      professional development opportunities increased from 2007 to 2010, likely
      reflecting the implementation of training sessions. The physical environment was
      the least satisfactory. This study highlights aspects of staff experience that
      have improved or still need to be improved since implementing a quality and
      safety program in our SMU.

PMID- 22953436
TI  - Screening, diagnosis, and treatment of post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is a prevalent problem among military
      personnel and veterans. Identification of effective screening tools, diagnostic
      technologies, and treatments for PTSD is essential to ensure that all individuals
      in need of treatment are offered interventions with proven efficacy. Well
      validated methods for screening and diagnosing PTSD are now available, and
      effective pharmacological and psychological treatments can be offered. Despite
      these advances, many military personnel and veterans do not receive evidence
      based care. We review the literature on screening, diagnosis, and treatment of
      PTSD in military populations, and discuss the challenges to implementing the best
      evidence-based practices in clinical settings.

PMID- 22953437
TI  - Prevention and care of combat-related PTSD: directions for future explorations.
AB  - In the past decade, military personnel supporting the wars in Iraq and
      Afghanistan have faced multiple deployments and repeated traumatic stressors.
      Despite efforts to prevent post-traumatic stress disorder (PTSD) and other combat
      related emotional difficulties, a significant number of military personnel
      experience psychological injuries during and following their deployments. Despite
      increased attention to prevention and treatment of these problems, it is clear
      that substantially more work is required to fully understand the emotional impact
      of combat and to better intervene to prevent potentially chronic problems. In the
      present article, the authors discuss possible avenues for future research and
      interventions (clinical and otherwise) to better prevent the development of
      combat-related PTSD. We discuss screening, assessment, education, and
      intervention for PTSD throughout the deployment cycle. In this discussion, we
      attend to both the needs of the current cohort of combat veterans and the
      potential advances that may mitigate the severity and chronicity of post
      traumatic problems arising from future conflicts.

PMID- 22953438
TI  - Epidemiology and prevention of substance use disorders in the military.
AB  - U.S. military service members have been in active combat for more than 10 years.
      Research reveals that combat exposure increases the risk of substance use
      disorders, post-traumatic stress disorder, major depression, and tobacco use. The
      Services and the field of addiction medicine are working hard to find a common
      definition for prescription drug misuse, which is a growing concern in both the
      general U.S. population and the force. Meanwhile, leaders at all levels of
      Department of Defense are diligently working to address barriers to care,
      particularly stigma related to substance abuse care, by seeking a balance between
      improving service member privacy in order to encourage self-referral for medical
      care and a commander's need to know the status of the unit and its combat
      readiness. The treatment and management of substance abuse disorders are a
      complex force health issue that requires the use of evidence-based medical
      interventions and policies that are consistent with them.

PMID- 22953439
TI  - Evidence-based screening, diagnosis, and treatment of substance use disorders
      among veterans and military service personnel.
AB  - Substance use disorders (SUDs) are among the most common and costly conditions in
      veterans and active duty military personnel, adversely affecting their health and
      occupational and personal functioning. The pervasive burden of SUD has been a
      continuing concern for the Department of Veterans Affairs (VA) and Department of
      Defense (DoD), particularly as large numbers of service members return from
      Operations Enduring and Iraqi Freedom. The VA and DoD have prioritized
      implementation of evidence-based practices and treatment services to enhance the
      recognition and management of SUD in general medical and SUD specialty-care
      settings. This article summarizes the clinical practice guidelines for
      identifying, diagnosing, and treating SUD in VA and DoD general medical and SUD
      specialty-care settings, highlights evidence-based pharmacotherapy and
      psychosocial interventions for managing SUD, and describes barriers to successful
      treatment of veterans and service members at risk for SUD in VA and DoD health
      care systems.

PMID- 22953440
TI  - Next steps in addressing the prevention, screening, and treatment of substance
      use disorder in active duty and veteran Operation Enduring Freedom and Operation
      Iraqi Freedom populations.
AB  - The two articles presented previously in this volume provide state-of-the-art
      reviews of the etiology, epidemiology, screening and treatment of substance use
      disorder (SUD). This article identifies next steps in research and development
      for understanding and treating SUD in Operation Enduring Freedom/Operation Iraqi
      Freedom service members and veterans. Four promising areas are reviewed: advances
      in psychopharmacological treatment of SUD, innovations in behavioral treatments,
      the use of technological advances for the screening and treatment of SUD, and
      integration of treatment services. Future directions are explored and suggestions
      for research, development and implementation of each of these trends are
      discussed.

PMID- 22953442
TI  - Screening, diagnosis, and treatment of depression.
AB  - The U.S. military and its civilian partners have identified that psychological
      health problems such as depression and traumatic brain injury represent a
      significant threat to the health and readiness of the military force. Depression
      is a growing problem in the military with rates increasing from 2007 to 2010
      across all services. Depression can be correlated with negative outcomes such as
      risk of suicide, risk of harm to others, incarceration, family problems including
      divorce, and occupational and social problems such as unemployment and
      homelessness. The military seeks to mitigate and prevent these negative outcomes
      through screening, diagnosis, and treatment of disorders such as depression. To
      support that effort, we have reviewed a sample of the literature base to support
      best practices for the screening, assessment, and treatment of depression within
      the Military Health System.

PMID- 22953441
TI  - Prevalence of DSM-IV major depression among U.S. military personnel: meta
      analysis and simulation.
AB  - A meta-analysis of 25 epidemiological studies estimated the prevalence of recent
      Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) major
      depression (MD) among U.S. military personnel. Best estimates of recent
      prevalence (standard error) were 12.0% (1.2) among currently deployed, 13.1%
      (1.8) among previously deployed, and 5.7% (1.2) among never deployed. Consistent
      correlates of prevalence were being female, enlisted, young (ages 17-25),
      unmarried, and having less than a college education. Simulation of data from a
      national general population survey was used to estimate expected lifetime
      prevalence of MD among respondents with the sociodemographic profile and none of
      the enlistment exclusions of Army personnel. In this Simulated sample, 16.2%
      (3.1) of respondents had lifetime MD and 69.7% (8.5) of first onsets occurred
      before expected age of enlistment. Numerous methodological problems limit the
      results of the meta-analysis and simulation. The article closes with a discussion
      of recommendations for correcting these problems in future surveillance and
      operational stress studies.

PMID- 22953443
TI  - Mild traumatic brain injury screening, diagnosis, and treatment.
AB  - The majority of combat-related traumatic brain injury (TBI) within the U.S. Armed
      Forces is mild TBI (mTBI). This article focuses specifically on the screening,
      diagnosis, and treatment aspects of mTBI within the military community.
      Aggressive screening measures were instituted in 2006 to ensure that the mTBI
      population is identified and treated. Screenings occur in-theater, outside the
      contiguous United States, and in-garrison. We discuss specific screening
      procedures at each screening setting. Current diagnosis of mTBI is based upon
      self-report or through witnesses to the event. TBI severity is determined by
      specific Department of Defense criteria. Abundant clinician resources are
      available for mTBI in the military health care setting. Education resources for
      both the patient and the clinician are discussed in detail. An evidence-based
      clinical practice guideline for the care of mTBI was created through
      collaborative efforts of the DoD and the U.S. Department of Veterans Affairs.
      Although symptoms following mTBI generally resolve with time, active treatment is
      centered on symptom management, supervised rest, recovery, and patient education.
      Medical specialty care, ancillary services, and other therapeutic services may be
      required.

PMID- 22953444
TI  - Diagnosis and management of moderate and severe traumatic brain injury sustained
      in combat.
AB  - Traumatic brain injury exists in a spectrum of severity among wounded personnel.
      The evaluation and clinical presentation, initial management, and treatment
      interventions to prevent secondary injury processes for combat-associated
      moderate and severe traumatic brain injury are reviewed. Promising therapies are
      discussed, and a current review of the literature is provided.

PMID- 22953445
TI  - Traumatic brain injury: next steps, research needed, and priority focus areas.
AB  - Traumatic brain injury (TBI) has been not only a major focus of concern during
      the recent conflicts in Afghanistan and Iraq, but also among our garrison service
      members. The prevalence of these injuries has compelled the nation and Congress
      to invest in the development of policies and programs that support evidence-based
      care for the full continuum of TBI, from mild (otherwise known as concussion) to
      severe and penetrating brain injuries. Although, the Department of Defense has
      made great strides in the areas of TBI clinical care, education, and research,
      there remains a great need to leverage scientific, policy, and clinical
      advancement to maximize care of the service member. The purpose of this article
      is to outline the 7 major areas of work currently being undertaken to help
      advance the field of TBI. The 7 areas include: (1) eliminating undetected mild
      traumatic brain injury through prompt early diagnosis, (2) ensuring force
      readiness and addressing cultural barriers, (3) improving collaborations with the
      Department of Veterans Affairs, other federal agencies, and academic and civilian
      organizations, (4) improving deployment-related assessments, (5) deploying
      effective treatments, (6) conducting military-relevant and targeted research, and
      (7) enhancing information technology systems.

PMID- 22953446
TI  - The influence of temperature on the effectiveness of filamentous bacteria removal
      from activated sludge by rotifers.
AB  - We investigated the feeding of the rotifer Lecane inermis on filamentous bacteria
      to determine if the ability of rotifers to remove filaments depends on
      temperature. The bacteria originated from two treatment plants, one of which was
      dominated by Microthrix parvicella and the other by Nostocoida limicola-like
      organisms. The experiments showed that the number of rotifers increased with
      temperature, and thus the ability of rotifers to reduce the number of filaments
      also increased with temperature. At 8 degrees C, their removal effectiveness was
      low, but the rotifers were able to survive at this temperature. When presented
      with sludge containing N. limicola-like microorganisms at 20 degrees C, the
      rotifers reduced the number of bacteria by 95%. In the case of M. parvicella, the
      reduction reached 50%. The results confirmed that Lecane are capable of
      controlling the growth of bacteria responsible for sludge bulking. This is the
      first report indicating that the seasonality of bulking may be the result of the
      activity of filamentous bacteria grazers, which is temperature dependent.

PMID- 22953447
TI  - Biodegradation of phenol by Ralstonia eutropha in a Kissiris-immobilized cell
      bioreactor.
AB  - This study examined the biodegradation of phenol by Ralstonia eutropha in a
      Kissiris-immobilized cell bioreactor (ICB), operated in a repeated batch
      recycling mode. The steady biodegradation rate of 23.7 mg/g/h, over a wide range
      of the initial phenol concentrations up to 1400 mg/L in the ICB, indicated an
      increased tolerance limit of the Kissiris-immobilized cells towards phenol. Both
      Haldane and Luong substrate inhibition models were used to describe
      biodegradation kinetic of free cells system. The Haldane equation gave the
      following values for the biokinetic parameters: micro(max) = 0.36 h(-1), Ks =
      40.48 mg/L, and Ki = 181.9 mg/L. However, according to the Luong model, these
      parameters were micromax) = 0.23 h(-1), Ks = 24.8 mg/L, Sm = 1018 mg/L, and n =
      1.3. By following appropriate operational conditions and use of the ICB, it was
      found to be possible to extend the efficiency of the highly porous structure of
      the siliceous mineral Kissiris in cell immobilization. This holds significant
      promise for pollutant biodegradation issues.

PMID- 22953448
TI  - Effects of impervious cover on the surface water quality and aquatic ecosystem of
      the Kyeongan stream in South Korea.
AB  - The extent of impervious cover in a watershed has been linked to the quality of
      an urban aquatic environment. The Kyeongan watershed in South Korea was
      investigated to evaluate the relationship between the total impervious area (TIA)
      and the aquatic ecosystem of the watershed, including water quality and aquatic
      life using a relatively high-resolution (0.4 m) image. The TIA was found to be
      approximately 12% of the watershed, which indicates that the quality of its
      environment was being adversely affected by it. For water quality, Pearson
      correlation analyses showed that all water quality parameters studied were found
      to be positively correlated with TIA at p < 0.01, except for nitrate (NO3-). In
      addition, the zone with a higher TIA was found to have worse water quality. Some
      water quality parameters, such as nitrite (NO2-), total phosphorus, and phosphate
      (PO4(3-)) were highly affected by discharges from wastewater treatment plants.
      Water quality data suggest that TIA could be used to predict the water quality of
      streams. For ecological parameters, the diatom index for organic pollution and
      trophic diatom index were found to be highly correlated with TIA, whereas
      physical habitat and benthic macroinvertebrates were poorly correlated with TIA.
      However, the results indicate that the extent of impervious cover can be a useful
      indicator for predicting the status of specific ecosystem of streams.

PMID- 22953449
TI  - Modeling external carbon addition in biological nutrient removal processes with
      an extension of the international water association activated sludge model.
AB  - The aim of this study was to expand the International Water Association Activated
      Sludge Model No. 2d (ASM2d) to account for a newly defined readily biodegradable
      substrate that can be consumed by polyphosphate-accumulating organisms (PAOs)
      under anoxic and aerobic conditions, but not under anaerobic conditions. The
      model change was to add a new substrate component and process terms for its use
      by PAOs and other heterotrophic bacteria under anoxic and aerobic conditions. The
      Gdansk (Poland) wastewater treatment plant (WWTP), which has a modified
      University of Cape Town (MUCT) process for nutrient removal, provided field data
      and mixed liquor for batch tests for model evaluation. The original ASM2d was
      first calibrated under dynamic conditions with the results of batch tests with
      settled wastewater and mixed liquor, in which nitrate-uptake rates, phosphorus
      release rates, and anoxic phosphorus uptake rates were followed. Model validation
      was conducted with data from a 96-hour measurement campaign in the full-scale
      WWTP. The results of similar batch tests with ethanol and fusel oil as the
      external carbon sources were used to adjust kinetic and stoichiometric
      coefficients in the expanded ASM2d. Both models were compared based on their
      predictions of the effect of adding supplemental carbon to the anoxic zone of an
      MUCT process. In comparison with the ASM2d, the new model better predicted the
      anoxic behaviors of carbonaceous oxygen demand, nitrate-nitrogen (NO3-N), and
      phosphorous (PO4-P) in batch experiments with ethanol and fusel oil. However,
      when simulating ethanol addition to the anoxic zone of a full-scale biological
      nutrient removal facility, both models predicted similar effluent NO3-N
      concentrations (6.6 to 6.9 g N/m3). For the particular application, effective
      enhanced biological phosphorus removal was predicted by both models with external
      carbon addition but, for the new model, the effluent PO4-P concentration was
      approximately one-half of that found from ASM2d. On a PO4-P removal percentage
      basis, the difference was small, that is, 94.1 vs. 97.1%, respectively, for the
      ASM2d and expanded ASM2d.

PMID- 22953450
TI  - Second-order chlorine decay and trihalomethanes formation in a pilot-scale water
      distribution systems.
AB  - It is well known that model-building of chlorine decay in real water distribution
      systems is difficult because chlorine decay is influenced by many factors (e.g.,
      bulk water demand, pipe-wall demand, piping material, flow velocity, and
      residence time). In this paper, experiments were run to investigate the kinetic
      model of chlorine decay and the formation model of trihalomethanes (THMs) in
      pilot-scale water distribution systems. Experimental results show that the rate
      constants of chlorine decay, including wall decay and bulk decay, increasing with
      temperature. Moreover, the kinetic model of chlorine decay and the formation
      model of THMs describe experiment data of pilot-scale water distribution systems.
      The effect of different piping material on chlorine decay and THMs formation were
      also investigated. The rate constants of chlorine decay are ranked in order:
      stainless steel pipe, ductile iron pipe, and last, polyethelene pipe because wall
      decay is the largest in stainless steel pipe than that in other piping material.
      Correspondingly, the rate of THMs formation follows the order of stainless steel
      pipe, ductile iron pipe, and last, polyethelene pipe because of less chlorine in
      bulk water reacting with the trihalomethane formation potential (THMFP).

PMID- 22953451
TI  - Environmental monitoring model for a drainage basin obtained through spectral
      analysis of time series.
AB  - The quality of results of an environmental monitoring plan is limited to the
      weakest component, which could be the analytical approach or sampling method.
      Considering both the possibilities and the fragility that sampling methods offer,
      this environmental monitoring study focused on the uncertainties caused by the
      time component. Four time series of nutrient concentration at two sampling points
      (PB1 and PB2) in the Ribeirao Garcia basin in Blumenau, Brazil, which were
      significantly correlated to the spatial component, were considered with a 2-hour
      resolution to develop efficient sampling models. These models were based on the
      time at which there was the highest tendency toward adverse environmental
      effects. Fourier spectral analysis was used to evaluated the time series and
      resulted in two sampling models: (1) the SMCP (sampling model for critical
      period) that operated with 100% efficiency for registering the highest
      concentration of nutrients and was valid for 83% of the studied parameters; and
      (2) the SMGCP (sampling model for global critical period) that operated with 83
      and 50% efficiency for PB1 and PB2, respectively.

PMID- 22953452
TI  - A new approach for the assessment of groundwater quality and its suitability for
      irrigation: a case study of the Korba Coastal Aquifer (Tunisia, Africa).
AB  - Groundwater is the main source of water in Mediterranean, water-scarce, semiarid
      regions of Tunisia, Africa. In this study of the Korba coastal aquifer, 17 water
      wells were studied to assess their suitability for irrigation and drinking
      purposes. Assessment parameters include pH, salinity, specific ion toxicity,
      sodium adsorption ratio, nutrients, trace metals pollutants, and fecal indicators
      and pathogens. Results indicate that salinity of groundwater varied between 0.36
      dS/m and 17.4 dS/m; in addition, its degree of restriction is defined as "none",
      "slight to moderate", and "severe" for 18, 23, and 59% of the studied wells,
      respectively. To control salts brought in by irrigation waters, the question
      arises as to how much water should be used to reach crop and soil requirements.
      To answer this question, a new approach that calculates the optimum amount of
      irrigation water considering the electrical conductivity of well water (ECw),
      field crops, and the semiarid meteorological local conditions for
      evapotranspiration and rainfall is developed. This is applied to the authors'
      case study area; barley and lettuce were selected among the commonly grown crops
      because they are high- and low-salinity tolerant, respectively. Leaching
      requirements were found to be independent of the crop selected, and depend only
      on the season, that is, 250 to 260 mm/month in the driest season, with a minimum
      of 47 mm/month though all seasons. A high bacteriological contamination appears
      in almost all samples. However, if disinfected and corrected for pH, all the well
      waters can be used for animal farming (including livestock and poultry), although
      only 29% could be used for human consumption.

PMID- 22953453
TI  - Removal of low concentrations of ammonium and humic acid from simulated
      groundwater by Vermiculite/Palygorskite mixture.
AB  - Contaminants in water are classified into different types based on their physical
      and chemical properties. Thus, more than one type of sorbents may be needed for
      their removal. In this article, a combination of vermiculite with palygorskite
      was studied for their simultaneous removal of ammonium and humic acid from
      simulated groundwater. Batch results showed that the Langmuir model described
      ammonium adsorption well with an adsorption capacity of 22 mg/g while the humic
      acid adsorption data fitted to the linear adsorption better, suggesting different
      removal mechanisms of these two types of contaminants. Kinetic studies showed an
      instantaneous removal of ammonium and humic acid. A column packed with mixture of
      equal volumes of vermiculite and palygorskite could treat 100 pore volumes for
      ammonium removal at an initial concentration of 10 mg/L and 500 pore volumes for
      humic acid removal at an initial concentration of 20 mg/L before the effluent
      concentrations exceeded the standard.

PMID- 22953454
TI  - Riding high on cloud 9.
AB  - Bath salts have become increasingly popular drugs of abuse. This has led to an
      increase in emergency department visits for patients with intoxication from these
      drugs. The literature indicates that bath salt intoxication can have significant
      physiological and psychiatric sequelae. The purpose of this article is to report
      data from 10 cases of bath salt intoxication that experienced severe psychiatric
      symptoms requiring emergency psychiatric detention (i.e. Physician Emergency
      Certificate). In general, our patients had mild sympathomimetic physiologic
      responses that resolved quickly. The psychiatric symptoms tended to be short
      lived, with staff psychiatrists rescinding the majority of the Physicians
      Emergency Certificates prior to inpatient admission. Our cases suggest that
      involuntary admission to psychiatric facilities may be circumvented with
      additional monitoring in the emergency department. Prospective studies should be
      done examining the natural course of bath salt-induced psychosis to determine if
      emergency detention is necessary.

PMID- 22953455
TI  - Successful transplantation of HIV patients: the Louisiana experience.
AB  - Human immunodeficiency virus (HIV) seropositivity has historically been an
      absolute contraindication for solid organ transplantation. However, the
      successful application of HAART (highly active anti-retroviral therapy) drug
      regimens has greatly prolonged the life expectancy of HIV-positive patients.
      Therefore, it has become appropriate to consider this patient population for
      transplantation. HIV positive transplants are being performed around the country
      in controlled settings, usually as part of a research protocol. The aim of our
      study is to describe the Louisiana experience with organ transplantation into HIV
      positive patients. We identified seven HIV-positive patients who underwent kidney
      or kidney/pancreas transplantation at our center between 2007 and 2010. We
      performed a retrospective chart review to ascertain graft function, as well as
      virologic and immunologic status post-transplant. Renal function (glomerular
      filtration rate and serum creatinine concentrations) improved in all subjects
      post-transplant, and six of seven (85.8%) subjects remained virologically
      suppressed with no progression to Acquired Immunodeficiency Syndrome (AIDS).
      Overall, two-year graft and patient survival rates were 85.5%. HIV seropositive
      End Stage Renal Disease (ESRD) patients represent a new population of patients
      that can be successfully transplanted. This offers a new dimension in care for
      successful HAART therapy to prolong the life of HIV-infected patients.

PMID- 22953456
TI  - Facial artery pseudoaneurysm after repair of mandibular fracture.
AB  - The authors report a case of a 59-year-old man involved in an assault that
      resulted in multiple mandibular fractures requiring surgical repair. He
      subsequently developed recurrent episodes of oral bleeding from a source that
      could not be identified by direct examination. Angiography of the external
      carotid artery identified a large pseudoaneurysm of the facial artery with
      extravasation. The patient underwent successful endovascular embolization without
      complication.

PMID- 22953457
TI  - A case series of Vibrio vulnificus infections in New Orleans, Louisiana.
AB  - OBJECTIVE: The objective of this study is to describe cases of V. vulnificus
      infection and to review the literature, emphasizing salient aspects of infection
      for practicing physicians. METHODS: A retrospective review of all patients aged 5
      years and older who grew V. vulnificus from a blood or tissue culture from 2005
      to 2011 at Tulane University Medical Center and Interim Louisiana Public
      Hospital. RESULTS: Six patients were identified over the study period. All were
      male and had a history of liver disease. Four developed primary septicemia and
      two developed wound infection with secondary septicemia. One received doxycycline
      as part of his antimicrobial therapy, which along with ceftazidime, is the
      recommended therapy for V. vulnficus infection. Four patients died despite
      aggressive care. CONCLUSIONS: V. vulnificus infection is an uncommon but often
      fatal cause of severe sepsis and wound infection. Physicians must recognize the
      clinical presentations of this infection in order to initiate early and
      appropriate therapy.

PMID- 22953458
TI  - Thyroid hemiagenesis.

PMID- 22953459
TI  - The syndromic classification, differential diagnosis, management, and prevention
      of potentially fatal plant poisonings in Louisiana and the Gulf South.
AB  - The American Association of Poison Control Centers has reported more than 50,000
      calls annually relating to plant exposures, usually non-lethal ingestions in
      young adults, adolescents, and children. In addition, there has been more than a
      100% increase in the mortality rate for unintentional poisonings in the United
      States (US) between 1999 and 2006, especially in males and in individuals aged 15
      29 years. For children, the frequency of plant exposures is directly related to
      their presence and abundance in households. In contrast, adolescents and young
      adults may experiment with naturally hallucinogenic plants, often obtained over
      the Internet, or attempt suicide by ingesting poisonous plants. In light of these
      recent trends in plant poisonings, the objectives of this investigation will be
      to propose a rapid syndromic classification scheme of only four types of highly
      toxic plants (cardiotoxic, neurotoxic, cytotoxic, and
      gastrointestinal/hepatotoxic) for the initial evaluation of patients poisoned by
      indigenous and often unidentified toxic plants in Louisiana and the Gulf South.
      It will also discuss current strategies for early diagnosis, management, and
      prevention of potentially lethal plant poisonings. Although many plants contain
      toxins, plants provide more than 70% of new drugs today and continue to provide
      new therapies for infectious diseases and cancer. More leisure time spent
      outdoors seeking natural foods and surfing the Internet for natural substances to
      abuse will create more opportunities for plant poisonings among high-risk groups,
      such as immigrants foraging for greens and adolescents experimenting with natural
      hallucinogens.

PMID- 22953460
TI  - An unexpected silver lining to Katrina: elimination of inter-campus transfer
      delay in STEMI care.
AB  - BACKGROUND: Timely primary percutaneous coronary intervention (PCI) is
      recommended for ST-elevation myocardial infarction (STEMI), with increasing focus
      being paid to the time required for inter-hospital transfer. An overlooked
      barrier to timely care is inter-campus transfer when the emergency department
      (ED) and cardiac catheterization lab (CCL) are in separate buildings. In August
      2005, Hurricane Katrina closed one campus of the Medical Center of Louisiana at
      New Orleans (MCLNO), forcing the ED and CCL to move into one building. We studied
      the impact of that closure on door-to-balloon times (DTB). METHODS: DTB for all
      STEMI patients between 1/04 and 6/11 were analyzed (as reported in MCLNO's Core
      Measures Report). National recommendations (i.e. single-pager activation, CCL
      ready within 30 minutes, etc.) were implemented prior to 2004; the consolidation
      of clinical services under one roof merely eliminated inter-campus transfer.
      RESULTS: In 2004-5, 28 patients presented with STEMI with a DTB of 156.5 +/- 62.6
      minutes. From 2006-11, 97 patients presented with STEMI with a DTB of 90.7 +/-
      54.3 minutes. The percentage of patients treated < or = 90 minutes increased from
      10.3% to 67.0%. CONCLUSIONS: Along with other measures to reduce DTB, attention
      needs to be focused on inter-campus transfer. Hospital design should include
      attention to this element of delay in care. The closure of one campus allowed for
      significant system improvement at MCLNO.

PMID- 22953461
TI  - Medications: a safety issue for biosimilars.

PMID- 22953462
TI  - Radiology case of the month: persistent lateral foot pain. Os peroneum pain
      syndrome.

PMID- 22953463
TI  - A 52-year-old woman with headache and bradycardia.
AB  - Cardiac sarcoidosis should be suspected in young patients with cardiac symptoms,
      especially when there is concurrent personal or family history of sarcoidosis.
      While sarcoidosis is self-limiting in about 40% of cases, cardiac involvement
      portends a more ominous prognosis with higher mortality rates. The definitive
      diagnostic test for cardiac sarcoidosis is the endomyocardial biopsy, an invasive
      test with low sensitivity. The multiple clinical modalities, which comprise the
      Japanese Ministry of Health clinical diagnostic guidelines, and newer modalities,
      including MRI, are more sensitive and demonstrate reliable diagnostic efficacy
      when compared to endomyocardial biopsy. Management of cardiac sarcoidosis
      involves early initiation of corticosteroid therapy to limit progression and
      maintain the structural and electrical integrity of the heart. When necessary,
      more invasive modalities (e.g. ICD, pacemaker, and transplant) may improve
      outcomes in advanced disease.

PMID- 22953464
TI  - Will the bugs win?

PMID- 22953465
TI  - State immunization law under review.

PMID- 22953466
TI  - A menace moves into the community.

PMID- 22953467
TI  - Wiser prescribing.

PMID- 22953468
TI  - A poke in the pocketbook.

PMID- 22953469
TI  - The cough that won't quit. Why Pertussis has made a comeback.

PMID- 22953470
TI  - The N of 1.

PMID- 22953471
TI  - Going home.

PMID- 22953472
TI  - Panel discussion delves into details of Supreme Court's ACA ruling.

PMID- 22953473
TI  - Vaccinations: A public health triumph and a public relations tragedy.
AB  - Routine vaccination has been hailed as one of the top public health achievements
      of the last century. However, despite the reduced number of cases of and deaths
      from vaccine-preventable diseases such as pertussis and measles, outbreaks
      continue to occur as more parents fail to adequately vaccinate their children
      because of misinformation about immunizations. This article describes the
      challenges of making sure all children in the United States are fully immunized
      and what physicians need to know to effectively work with parents who may be
      hesitant to vaccinate their children.

PMID- 22953474
TI  - Tick-borne diseases in Minnesota: an update.
AB  - Tick-borne diseases endemic to Minnesota include Lyme disease, babesiosis,
      anaplasmosis/ehrlichiosis, Powassan virus illness and Rocky Mountain spotted
      fever. Physicians need to be aware of these diseases and be vigilant about
      testing for them when patients present with acute febrile illness or rash within
      one month of potential tick exposure. In addition, they need to educate patients
      about these diseases and encourage prevention measures, especially use of tick
      repellents. This article reviews the epidemiology of these illnesses in Minnesota
      and the current recommendations for diagnosis and treatment.

PMID- 22953475
TI  - Streptococcus pneumoniae serotypes: nine-year experience at a level-one trauma
      center.
AB  - Streptococcus pneumoniae isolates from adults hospitalized with invasive
      pneumococcal disease (IPD) were collected at Regions Hospital in St. Paul from
      2002 through 2010. Of 200 sequential, nonduplicative isolates collected and
      serotyped, serotypes 3, 7F and 19A were found to be the most common. Since 2008,
      all IPD cases have been caused by non-PCV7 serotypes. This article describes the
      study and its findings. It also provides an overview of the three vaccines used
      to protect against IPD.

PMID- 22953476
TI  - Antiretroviral medications as prevention: will the new paradigm reverse the HIV
      epidemic?
AB  - Fifteen years after recognition of the AIDS epidemic, the development of potent
      antiretroviral therapy (ART) resulted in a significant reduction in HIV-related
      morbidity and mortality for persons in resource-rich regions of the world. Now 30
      years after the HIV/AIDS epidemic began, we have learned that potent ART also
      decreases transmission of HIV and that judicious use of antiretroviral
      medications in people who do not have the virus but are at high risk for
      contracting it (pre-exposure prophylaxis or PREP) can protect against HIV
      infection. We now have the necessary tools to significantly decrease the scope of
      the epidemic in the decades ahead. Whether we use them-that is, provide
      antiretrovirals prophylactically or conduct widespread testing for HIV and treat
      all people who are found to have the virus-will depend on the concerted actions
      of societies, governments, public health authorities, clinicians and individuals.

PMID- 22953477
TI  - Eat your broccoli--or else!

PMID- 22953478
TI  - Affordable Care Act: Your economic future still up for debate.

PMID- 22953479
TI  - Ready for 32 million new patients? ACA's impact forever changes healthcare
      financing and access to care.

PMID- 22953480
TI  - Reimbursement realities: While Medicaid rates go up, payers pull away from fee
      for-service model.

PMID- 22953481
TI  - Could an in-house lab be right for your practice? With proper planning, this
      ancillary service may boost practice income and save valuable time.

PMID- 22953482
TI  - Focus on the facts: When deciding whether an in-house lab is right for your
      practice, calculate the costs and revenues you may incur.

PMID- 22953483
TI  - Survey identifies keys to EHR implementation success: Hiring outside help,
      purchasing quality hardware, and getting staff buy-in all important in this phase
      of adding technology.

PMID- 22953484
TI  - Reaching the finish line: Physician ranks as one of the first in EHR study to
      attest for meaningful use, and she's still smiling.

PMID- 22953485
TI  - Understanding the true costs of an EHR implementation: Plan for unanticipated
      expenses so they don't slow your progress or delay a 'return to normalcy'.

PMID- 22953486
TI  - Update vaccine code before flu season arrives.

PMID- 22953487
TI  - Beware legal ramifications of unnecessary tests.

PMID- 22953488
TI  - What we can learn from the French: examining another system can help diagnose
      problems with U.S. healthcare.

PMID- 22953489
TI  - Austerity program: States keep an eye on Mass. legislation limiting annual
      healthcare expenditures.
AB  - Massachusetts' landmark bill to contain healthcare spending has the attention of
      policymakers nationwide, as they wait to see which approaches in the law work.
      "This is a broad bill that uses a lot of different levers to make progress on
      healthcare affordability," says Sarah Iselin, left, of the Blue Cross and Blue
      Shield of Massachusetts Foundation. "It's a complex challenge, and if there were
      one silver-bullet solution, we'd all be doing it."

PMID- 22953490
TI  - Accretive exits Minnesota...but questions linger over collection practices.

PMID- 22953491
TI  - Time for an update: Health data breaches cited in GAO's call for fix.

PMID- 22953492
TI  - Inside CMS' war room: The battle against fraud comes under scrutiny.

PMID- 22953493
TI  - Ripple effect: Research office seen as turning point in ER care.

PMID- 22953494
TI  - Drawing attention: Whistle-blowers follow spotlight to Nashville.

PMID- 22953495
TI  - Learning curve: Romney praise of Israeli system draws unfavorable contrasts with
      U.S.

PMID- 22953496
TI  - Resistance movement: Hospital administrators must join the fight against
      antibiotic overuse.

PMID- 22953497
TI  - Outpatient care takes the inside track.

PMID- 22953498
TI  - Integrative innovator: Raby Institute founder and leader named Physician
      Entrepreneur of the Year.

PMID- 22953499
TI  - Health care's new maverick.

PMID- 22953500
TI  - IgG4-related disease.
AB  - IgG4-related disease (IgG4-RD) is considered a fibro-inflammatory condition with
      a marked propensity to form mass forming lesions, characterized by a dense
      lymphoplasmacytic infiltrate, the presence of abundant IgG4+ plasma cells,
      frequent elevation of serum IgG4 and a dramatic initial response to
      glucocorticoid. Nowadays, IgG4-RD has been described in almost every organ
      system: the pancreatobiliary tract, liver, salivary glands, nasopharynx, bone
      marrow, lacrimal gland, extra-ocular muscles and retrobulbar space, kidneys,
      lungs, lymph nodes, meninges, aorta and arteries, skin, breast, prostate, thyroid
      gland and pericardium. Although the common diagnostic features of all these
      regional involvements cannot be defined with certainty, and slight differences
      have been noted in different organs, many histopathological features are shared.
      Consensus has not yet been reached regarding criteria that have to be fulfilled
      for a new IgG4-RD. The proposed criteria include appropriate clinical and
      histopathological findings, presence of abundant tissue-infiltrating IgG4+ plasma
      cells, high serum IgG4 concentrations, response to steroid therapy, other
      autoimmune diseases or other organ involvement. The two hallmark features for
      diagnosis are histopathological characteristics and the presence of infiltrating
      IgG4+ plasma cells. In this review, we will focus on the histopathological
      features of IgG4-RD in specific organs and discuss the relationship with
      inflammatory pseudotumour and malignancy, IgG4 counting methods, and diagnosis
      using biopsy specimens. IgG4-related disease (IgG4-RD) is a multi-organ system
      disease that has been recognized in the last 10 years. IgG4-RD has a marked
      propensity to present as mass-forming lesions. The two hallmark features for
      diagnosis are histopathological characteristics and the presence of infiltrating
      IgG4+ plasma cells. Correct identification is crucial to avoid unnecessary major
      surgical procedures and initiate corticosteroid therapy.

PMID- 22953502
TI  - Diagnostic role of rapid on-site cytologic examination (ROSE) of broncho-alveolar
      lavage in ALI/ARDS.
AB  - BACKGROUND: While bronchoscopy should be considered in patients with acute lung
      injury (ALI) and acute respiratory distress syndrome (ARDS) in which the cause
      cannot be determined from history or clinical and laboratory data, there are no
      studies about the utility of rapid on-site examination (ROSE) of broncho-alveolar
      lavage for identification, as early as possible, of the pathological condition
      underlying the onset of this condition. The aim of this prospective,
      observational study was to evaluate the diagnostic role of ROSE of BAL in
      ALI/ARDS. METHODS: 71 patients with ALI/ARDS underwent bronchoalveolar lavage,
      and one part of the sample was examined with ROSE. The on-site report was
      categorized as diagnostic (specific diagnosis), presence of atypical reactive
      type II pneumocytes with no further comments or not diagnostic. RESULTS: ROSE of
      bronco-alveolar lavage yielded 29 (41%) specific diagnoses, revealed typical
      features of diffuse alveolar damage without a specific diagnosis in 28 patients
      (39%) and did not reveal a specific diagnosis in the remaining 14 cases (20%).
      CONCLUSIONS: The results of this study show that, in patients with ALI/ARDS,
      bronchoalveolar lavage with ROSE is diagnostic in 40% of cases: ROSE may
      therefore spare lung biopsies and improve the prognosis of patients with ARDS
      (immunocompetent or not) as therapy could be started or modified at a very early
      phase.

PMID- 22953501
TI  - Expression of the CD2AP adaptor molecule in normal, reactive and neoplastic human
      tissue.
AB  - AIMS: To study the expression of CD2-associated protein (CD2AP), an adaptor
      protein involved in T-cell signalling and renal function, in normal, reactive and
      neoplastic human lymphoid tissues. METHODS AND RESULTS: We used
      immunohistochemical techniques to evaluate monoclonal antibodies against CD2AP on
      over 400 formalin fixed paraffin embedded tissue blocks retrieved from the host
      institutions of three authors. The samples tested included normal, reactive and
      neoplastic lymphoid tissue. In lymphoid tissues, strong CD2AP staining was
      observed in plasmacytoid dendritic cells (pDCs), weak and variable in mantle zone
      B cells and moderate in rare germinal center cells. CD2AP labeled cortical and
      rare medullary thymocytes and isolated mononuclear cells in bone marrow
      trephines. Furthermore, epithelial and endothelial cells expressed CD2AP. Among
      neoplasms, the greatest number of CD2AP-positive cases were found in diffuse
      large B cell (21/94), NK T-cell lymphomas (7/67), "blastic plasmacytoid dendritic
      cell neoplasms" (9/10) and some types of solid tumor. CONCLUSIONS: Our finding
      that mature peripheral T cells are CD2AP-negative but immature cortical
      thymocytes are positive may prove useful for diagnostic purposes. Moreover, our
      results demonstrate that CD2AP represents a useful marker of normal and
      neoplastic pDC and may be used in a diagnostic panel in reactive or neoplastic
      lymphoid proliferations.

PMID- 22953503
TI  - Theory and practical application of superficial atypical melanocytic
      proliferations of uncertain significance (SAMPUS) and melanocytic tumours of
      uncertain malignant potential (MELTUMP) terminology: experience with second
      opinion consultation.
AB  - INTRODUCTION: The term superficial atypical melanocytic proliferations of
      uncertain significance (SAMPUS) is used to resolve discordance in diagnosis of
      "thin" melanocytic lesions. Melanocytic tumours of uncertain malignant potential
      (MELTUMP) is the descriptive term for an ill-defined group of dermal melanocytic
      tumours that exhibit features indicative of possible malignancy. We report our
      experience of collaboration with two leading international consultant
      pathologists in the diagnosis of melanoma in order to facilitate the practical
      application of the term SAMPUS and MELTUMP. METHODS: Twenty-seven cases of
      melanocytic lesions with interpretative problems were sent for consultation to
      Expert #1 (15 cases) and Expert #2 (12 cases). RESULTS: Two cases of MELTUMP and
      two cases of SAMPUS were diagnosed by Expert #1; three cases of MELTUMP and two
      cases of SAMPUS were diagnosed by Expert #2. Diagnosis was performed with H&E and
      molecular studies were not performed. DISCUSSION: Both experts included MELTUMP
      or SAMPUS atypical, ambiguous melanocytic lesions and melanomas. The diagnosis of
      SAMPUS and MELTUMP by consultant pathologists reflects the difficulty of
      classification with accuracy lesions that showed histological features of various
      atypical tumours or malignant melanoma. In these cases, biological potential may
      be established with molecular studies.

PMID- 22953504
TI  - Primary cutaneous aggressive epidermotropic CD4/CD8 double-negative cytotoxic T
      cell lymphoma.
AB  - The classification of cutaneous T-cell lymphomas (CTCL) is based on clinical,
      histological and immunohistochemical findings. Diagnosis may be difficult given
      the significant heterogeneity of these tumours. We describe herein an original
      case of primary cutaneous aggressive epidermotropic CD4/CD8 double-negative
      cytotoxic T-cell lymphoma that illustrates the difficulty in classification.

PMID- 22953505
TI  - Adrenal epithelial cyst: a case report.
AB  - Epithelial-lined or true cysts of the adrenal gland are exceedingly rare
      accounting for only 9% of all adrenal cysts. A 55-year-old woman with a medical
      history for cholecystectomy and liver hydatidosis presented with an 8-month
      history of abdominal pain in the upper left quadrant. Physical examination was
      unremarkable and laboratory tests were within normal range. Computed tomography
      displayed a homogeneous and finely calcified cystic mass of the left adrenal
      gland measuring 12 x 10 cm. A hydatid cyst of the adrenal gland was suspected
      preoperatively and the patient underwent uneventful excision of the cyst.
      Histological examination of the surgical specimen revealed that the cyst wall was
      lined by cuboidal to flattened cells with bland cytologic features.
      Immuohistochemically, the cyst lining expressed intensely cytokeratin but was
      negative for CD 34 and calretinin. The final pathological diagnosis was
      epithelial adrenal cyst.

PMID- 22953506
TI  - Cervical lymph node metastasis of adenocarcinoma of prostatic origin.
AB  - Cervical nodes metastases generally arise from carcinomas of the head and neck,
      but also from other organs. This report describes a case with metastatic prostate
      cancer in the cervical lymph node.

PMID- 22953507
TI  - Participants with prolonged grief--how do they benefit from grief group
      participation?
AB  - Data analyzed in this article is part of a study conducted to explore grief
      support groups in Norway. Participants that fulfilled the criteria of Prolonged
      Grief Disorder (PGD) were compared with participants that did not in order to
      explore whether they differed on satisfaction and experiences with participation.
      To allow for comparison, a subsample of 22 participants that fulfilled the
      criteria of PGD were drawn from the total of 262 participants. Demographic and
      loss-related variables were analyzed to explore factors associated with PGD.
      Fulfillment of PGD was then analyzed to explore the group's effect on life
      quality and overall satisfaction. The main finding is that participants who
      fulfill the criteria of prolonged grief are in general less satisfied with the
      groups and report less positive effect on life quality. We also found age- and
      gender-differences regarding fulfillment of PGD, with older bereaved women
      especially at risk of developing symptoms of PGD.

PMID- 22953508
TI  - Considerations for grief interventions: eras of witnessing with families.
AB  - This article describes research that was conducted to articulate interventions
      with families experiencing grief. Using an interpretive methodology framed by
      philosophical hermeneutics allowed for a depth of understanding of these
      therapeutic conversations. The research findings offer explanations of the role
      of time in relation to grief, particularly the timing of interventions, and
      describe the significance of working with multiple family members during
      therapeutic interventions. This research was unique in that it approached grief
      counseling with a family focus, the participants were interviewed for this study
      several years after the therapeutic encounter, and the underlying theoretical
      framework for the interventions focused on grief as a lifelong, life-changing
      experience, rather than a finite, pathology-laden event.

PMID- 22953509
TI  - Barriers to completion of advance care directives among African Americans ages 25
      84: a cross-generational study.
AB  - Prior studies conducted in the area of Advance Care Directive document completion
      in African Americans have primarily targeted the elderly who are either
      institutionalized in skilled nursing facilities or are members of faith
      communities. Few studies have been done concerning barriers to Advance Care
      Directive document completion that include non-elderly African Americans. The
      purpose of this study was to identify the common barriers to advance care
      directive document completion across generations of African Americans ages 25-84.
      Using convenience sampling among various Baptist denominations of the African
      American faith community of Buncombe County, North Carolina, 40 individuals
      ranging in age from 25-84 participated in multiple focus group sessions. Findings
      revealed participants shared three common barriers: 1) surrogate decision-making,
      2) lack of education concerning advance care directive discussions and
      completion, and 3) fear and denial. Also revealed were barriers that varied
      across generations: 1) fatalism, 2) mistrust of the health care system, 3)
      spirituality, and 4) economics.

PMID- 22953510
TI  - Efficacy of writing for recovery on traumatic grief symptoms of Afghani refugee
      bereaved adolescents: a randomized control trial.
AB  - Effective evidence-based intervention for traumatic bereavement is one of the
      current major research issues in the field of Post Traumatic Stress Disorder
      (PTSD) in children and adolescents. The "Writing for Recovery" group intervention
      is a new treatment approach developed by the Children and War Foundation for
      traumatized and bereaved children and adolescents after disasters. The purpose of
      this project was an empirical examination of this intervention with 12- to 18
      year-old war bereaved Afghani refugees. Eighty-eight war bereaved Afghani
      refugees were screened using the Traumatic Grief Inventory for Children (TGIC).
      From those with the highest total score, 61 were randomly assigned to either an
      experimental (n = 29) or control group (n = 32). The experimental group received
      six sessions of group training on 3 consecutive days in their school. The
      difference of TGIC scores between the experimental group in pretest and posttest
      was significant (p = 0.001). Results of analysis of covariance also showed a
      significant effect of Writing for Recovery on the experimental group (p < 0.001).
      It is concluded that "Writing for Recovery" is an effective group intervention
      for bereaved children and adolescents after disasters.

PMID- 22953512
TI  - Candidal endocarditis presenting with bilateral lower limb ischemia.
AB  - The incidence of fungal endocarditis is increasing. While the pathogenic
      mechanisms are not fully understood, infection is associated with underlying
      heart disease and is most often attributable to Candida species. Candidal
      endocarditis complications include heart damage, inflammation, and emboli with
      resulting ischemia and tissue death. Candidal endocarditis is difficult to
      diagnose as blood cultures are often negative. Treatment includes surgical
      intervention and antifungal therapy. This case study describes a 41-year-old
      female complaining of acute onset of pain with numbness and tingling in both
      lower extremities. Prior history was significant for mycotic valve aneurysm and
      replacement secondary to culture-negative endocarditis. Evidence of limb
      threatening ischemia led to a bilateral thrombectomy. During the thrombectomy
      white debris, later identified as Candida albicans, was encountered. A
      transesophogeal echocardiogram revealed a pedunculated mass which was determined
      to be the source of infection. The patient was placed on micafungin and
      voriconazole and discharged with a diagnosis of C. albicans fungal infection with
      descending aorta fungal mass. This case study illustrates an unusual presentation
      of candidal endocarditis with discussion of disease epidemiology, pathogenesis,
      diagnosis, and treatment.

PMID- 22953511
TI  - Conceptual and design issues in instrument development for research with bereaved
      parents.
AB  - Many childhood deaths in the United States occur in pediatric intensive care
      units (PICUs) and parents have special needs in this death context. As an
      interdisciplinary research team, we discuss conceptual and design issues
      encountered in creating a new instrument, the Bereaved Parent Needs Assessment
      PICU, for assessing parents' needs in this setting. Using a qualitative approach,
      our team previously explored how the culture and related ways of providing care
      in one urban Midwestern children's hospital PICU affected parents' bereavement
      needs and experiences. We describe using this qualitative foundation in the
      development of a new quantitative instrument to more widely validate and measure
      bereaved parents' needs around the time of a child's death across multiple PICUs.
      We highlight a series of issues that warrant consideration in designing a
      research instrument for this vulnerable population including setting and context,
      format and content, temporality, recruitment, and content expertise.

PMID- 22953513
TI  - Usefulness of cumulative summation of differences method for determining APTT
      reagent suitability.
AB  - OBJECTIVE: The Cumulative Summation of Differences (CUSUM) is a recommended
      method for determining the consistency of one lot of Activated Partial
      Thromboplastin Time (APTT) reagent to another. This study investigates the
      usefulness of the CUSUM as a primary method for determining reagent suitability
      for APTT testing. METHOD: Results for lot comparison, reference range and Ex-Vivo
      heparin sensitivity studies were obtained using the Beckman Coulter ACL TOP
      coagulation analyzer. APTT testing was performed using HemosIL SynthASiL w/CaCl
      and Heparin Xa testing was performed using the HemosIL Liquid Heparin Assay.
      Samples from normal patients and from patients taking heparin were tested.
      RESULTS: The CUSUM calculation showed a difference in APTT reagent lot means that
      is within the acceptable range for this method, suggesting that the reagents were
      comparable. Reference range and heparin sensitivity studies demonstrated a
      clinically significant difference between the two reagent lot numbers tested.
      CONCLUSION: The CUSUM method of evaluating reagent lot variation of APTT reagents
      should be used with caution as it may not completely reflect the performance of
      the reagent. Clinically significant differences between reagent sensitivity may
      not be detected. The results of reference range and heparin sensitivity studies
      should also be considered when determining the suitability of APTT reagents. In
      addition, due to research evidence that using the APTT test for monitoring
      patient anticoagulation therapy is problematic, an evaluation of the benefits of
      using other study methods and multiple study methods is suggested as well as
      continued examination of the use of the APTT as the test of choice for UF heparin
      monitoring.

PMID- 22953514
TI  - Implementing virtual microscopy improves outcomes in a hematology morphology
      course.
AB  - In this study, we evaluated the efficacy of virtual microscopy as the primary
      mode of laboratory instruction in undergraduate level clinical hematology
      teaching. Distance education (DE) has become a popular option for expanding
      education and optimizing expenses but continues to be controversial. The
      challenge of delivering an equitable curriculum to distant locations along with
      the need to preserve our slide collection directed our effort to digitize the
      slide sets used in our teaching laboratories. Students enrolled at two
      performance sites were randomly assigned to either traditional microscopy (TM) or
      virtual microscopy (VM) instruction. The VM group performed significantly better
      than the TM group. We anticipate that this approach will play a central role in
      the distributed delivery of hematology through distance education as new programs
      are initiated to address workforce shortage needs.

PMID- 22953515
TI  - Snapshot prevalence and characterization of Staphylococcus species, including
      MRSA, in a student athletic facility: an undergraduate research project.
AB  - OBJECTIVE: To evaluate and characterize the prevalence of MRSA, Staphylococcus
      aureus, and other Staphylococcus species found on exercise equipment on one day
      point of collection. DESIGN: A cross sectional, point prevalence design (pilot
      study) with a single time of measurement. Data collected in summer of 2011
      (Undergraduate Research Project for CLS Program, CLS 4361 Clinical Research).
      Project received Institutional Review Board exemption. SETTING: In a higher
      education athletic facility in Texas. SAMPLES: One hundred twenty-five
      environmental samples were collected from various exercise equipment and areas
      within the facility. MAIN OUTCOME MEASURES: Samples were screened for
      Staphylococcus species using standard microbiological techniques. Confirmation of
      S. aureus was conducted by DRYSPOT Staphytect Plus. MRSA isolates were confirmed
      with CHROMagar; VITEK 2 antibiotic susceptibility testing and PFGE characterized
      all MRSA isolates. RESULTS: Prevalence of MRSA was 6%, S. aureus 38%, other
      Staphylococcus species 52% and no growth 4%. Prevalence of S. aureus and MRSA was
      highest on free weights and mats, respectively. PFGE characterized all MRSA
      isolates as HA-MRSA (USA100 strain). CONCLUSIONS: Although limitations exist for
      this study with a single time of measurement for data, the findings indicate
      potential exposure risks from Staphylococcus species in college athletic
      facilities. Compliance (disinfection) and creative health education may reduce
      transmission of pathogens, environmental load, and incidence of colonization or
      infection in students.

PMID- 22953516
TI  - Lupus anticoagulant increases activated partial thromboplastin time (PTT)
      prolongation in incubated 1:1 mix.
AB  - Our study analyzes the effects of incubation time and strength of lupus
      anticoagulant (LAC) on clotting times and prolongation of activated partial
      thromboplastin time (PTT) 1:1 mix assays with incubation. The prolongation in
      seconds of PTT 1:1 mix after incubation in the confirmed presence or absence of
      LAC was correlated to strength of the LAC as well as length of incubation (1 vs.
      2 hours). Our study suggests that when screening for possible Factor VIII (FVIII)
      inhibitors, a 2 hour incubation of a PTT 1:1 mix increases the frequency of false
      positives as compared to 1 hour incubation, and that most of these false
      positives are due to LACs. Prolongation of clotting times for PTT 1:1 mixes in
      patients with LAC is influenced by both length of incubation time and strength of
      the LAC. CONCLUSIONS: When using PTT 1:1 mixes to screen for FVIII inhibitors,
      the effect of a possible LAC on the interpretation of the PTT prolongation should
      be considered. This effect is influenced by both incubation time and LAC
      strength.

PMID- 22953517
TI  - Updates in immunoassays: introduction.

PMID- 22953518
TI  - Updates in immunoassays: bacteriology.
AB  - There are many immunoassays available that provide rapid, accurate and sensitive
      results. The intent of this article was to provide a brief overview of some of
      the products and methodologies available for clinical use and to discuss some of
      the principles behind the methodology and instrumentation. In the area of
      infectious disease, the use of immunoassays ensures rapid turnaround times that
      will result in the administration of prompt, accurate treatment for the patient.
      Ultimately, this will improve overall patient outcomes while possibly decreasing
      the costs associated with increased hospital stay. In conclusion, immunoassays
      are essentially easy to perform, cost-effective, produce highly sensitive and
      specific results, and allow the medical laboratory professional the ability to
      report accurate results in a timely manner.

PMID- 22953519
TI  - Updates in immunoassays: virology.
AB  - Virus identification is a challenge to the clinical microbiologist since growing
      viruses in traditional cell culture is labor intensive, time consuming, and
      subject to contamination. The advent of rapid and automated immunoassays has
      eliminated this problem by generating positive results in minutes to hours. For
      example, testing for infectious mononucleosis can yield a positive result in 3-8
      minutes as seen with the Beckman Coulter, Inc. ICON Mono test or in 5-15 minutes
      with the MONO Mononucleosis Rapid Test Device marketed by ACON Laboratories, Inc.
      Fully automated immunoassay analyzers provide fast, accurate, sensitive results
      that aid in a prompt and accurate diagnosis for the patient. Turnaround times are
      shortened, allowing for timely medical intervention and treatment. The priority
      in any hospital or medical facility is to treat the patient as quickly and
      appropriately as possible. By using immunoassays, clinical laboratory
      professionals are able to report out correct results in a timely manner, ensuring
      overall positive patient outcomes and improved quality of healthcare.

PMID- 22953520
TI  - Updates in immunoassays: parasitology.
AB  - Although most clinical laboratories use microscopy and routine O&P procedures
      when identifying parasitic infections, there are several parasites that are
      better detected through serological means. Toxoplasma, Giardia, and
      Cryptosporidium were discussed along with immunoassays used for their detection.
      Immunoassays provide quick results and are less labor intensive than specimen
      concentration and slide preparation for microscopic examination. These assays are
      easy to use and provide sensitive and specific results. Some clinical
      laboratories no longer perform O&Ps in house and refer specimens to reference
      laboratories for evaluation. By using immunoassays, some of the more common
      parasites can be identified in a timely manner reducing turn-around times. Some
      controversy exists over the use of IIF and EIA tests used for ANA testing along
      with measuring CRPs and PCT as predictors of bacterial sepsis and septic shock.
      Regardless of the methodology discussed in this series of articles, there are
      pros and cons to the various immunoassays available. Determining the most
      appropriate assay based on patient population and volume is governed by the
      institution and its patients' needs. In conclusion, immunoassays, whether manual
      or automated, are easy to use, cost effective and allow the medical laboratory
      professional to provide quick and accurate results to the clinician so the most
      appropriate treatment can be administered to the patient. The ultimate goal of
      healthcare professionals is to provide the highest quality of medical care in a
      timely manner. The use of immunoassays in the clinical laboratory allows the
      healthcare team to successfully achieve this goal.

PMID- 22953521
TI  - We need a tooth campaign.

PMID- 22953522
TI  - The case for zirconia crowns.

PMID- 22953523
TI  - The CDA Foundation model to fluoridate communities.
AB  - California's population receiving the benefits of fluoridated public water
      supplies has increased from 15.7 percent to 62.1 percent in the past 20 years.
      This growth has been achieved through a broad-based coalition of organizations
      and individuals, starting with the creation of the California Fluoridation Task
      Force in 1994 and supported by the California Fluoridation Act of 1995. This
      paper describes the process whereby the most recent gains have been made in San
      Diego and are ongoing in San Jose.

PMID- 22953524
TI  - Idiopathic synchronous central giant cell granulomas involving both the maxilla
      and mandible: a case report.
AB  - The central giant cell granuloma is a well-defined lesion of the jaws and reports
      of multiple lesions are very uncommon. The authors report the case of a patient
      with idiopathic synchronous multiple central giant cell granulomas involving both
      the maxilla and the mandible. Surgical curettage of the lesions was performed. At
      the end of the 24 months follow-up, no recurrence was detected.

PMID- 22953525
TI  - Medication nonadherence: a role for the dental professional.
AB  - Medication nonadherence is a multifactorial and complex problem that poses an
      enormous health and economic burden. Medication nonadherence related to
      medication side effects, referred to as rational nonadherence is increasingly
      seen in patients. This article discusses rational nonadherence with an exemplar
      of osteoporosis patients discontinuing their medication, mainly bisphosphonates,
      for fear of complications such as osteonecrosis of jaw. Also, the possible role
      of dental professionals in overcoming medication nonadherence in general is
      outlined.

PMID- 22953526
TI  - Sleep bruxism, an autonomic self-regulating response by triggering the trigeminal
      cardiac reflex.
AB  - Sleep bruxism, an intensified manifestation of rhythmic masticatory muscle
      activity, characterized by tooth grinding or clenching during sleep, lacks a
      definitive physiological purpose. This paper posits that physiologically, sleep
      bruxism is an autonomic self-regulatory response to nighttime occurrences of
      tachycardia stemming from the brain experiencing microarousals during sleep.
      Sleep bruxism by triggering the trigeminal cardiac reflex leads to bradycardia.
      Rhythmic masticatory muscle activity-sleep bruxism, thereby, serves to slow the
      heart rate when brain microarousals cause tachycardia.

PMID- 22953527
TI  - An emperor's brush with ingenuity.

PMID- 22953528
TI  - The evolving physician practice in the post-reform era.

PMID- 22953529
TI  - Delaware Cancer Registry modernization.
AB  - This article discusses the background and future plans of the Delaware Cancer
      Registry pertaining to its history, case reporting requirements, goals for
      accurate cancer data, and its path towards implementation of a new cancer data
      information system, the Centers for Disease Control and Prevention's Registry
      Plus.

PMID- 22953530
TI  - The founders of the Medical Society of Delaware. Doctor William Molleston.

PMID- 22953531
TI  - Securing and protecting electronic medical records.

PMID- 22953532
TI  - Shifting standards of care.

PMID- 22953533
TI  - [Neuromediators and neurotransmitters in the bone tissue remodeling].
AB  - The review is devoted to the molecular mechanisms of bone resorption with
      recruitment of neuromediators and neurotransmitters executing the ladder
      processes of neuronal regulation and directly stimulating serotonergic,
      adrenergic, glutamatergic and GABA-ergic receptors of osteoblasts and
      osteoclasts. Microgravity-induced elevation of the sympathetic nervous system
      tone is considered a likely factor in the increase in bone resorption rate during
      long-duration space flight.

PMID- 22953534
TI  - [Aviation noise: specifics of the biological action and protection].
AB  - Purpose of the work was to examine the acoustic and work environment of air
      forces personnel, to look for the specific effects of aviation noise on human
      organism, and to put out evidence-based guidelines for protection. On-site
      acoustics measurements, hygiene inspection of labor conditions and analysis of
      disease incidence including review of clinical investigations results were
      carried out. It was demonstrated that the aviation noise spectrum spreads to the
      sound and infrasound high-frequency bands referring the aviation personnel
      environment to class 3.2-4 of harmful and hazardous occupations. The combination
      of noise and infrasound provokes specific (occupational) and nonspecific
      diseases. Choice of the protectors should be made with consideration of specifics
      of the biological effects of aviation noise.

PMID- 22953535
TI  - [Neuromorphological effects of low doses of ionizing radiation].
AB  - Morphological methods were used to study several segments of the rat's brain
      after gamma-irradiation by 10, 20, 50 and 100 cSv. Tissue samples were
      investigated shortly after dose delivery, in 24 hours, and after 6, 12, 18 and 24
      months since irradiation. Neurons were shown to be sensitive to radiation.
      Conventionally, the nervous system reaction can be segmented into three stages,
      i.e. an early response (initial 30 days), revealed changes (by mo. 6) and repair.
      Life span of irradiated animals was not altered; however, individual
      morphological variations and even incomplete repair may affect quality of life of
      radiation disaster fighters and population of contaminated regions.

PMID- 22953536
TI  - [Shifts in the mice blood-forming system and energy exchange of erythrocytes due
      to chronic exposure to chemical agents (acetone, ethanol, acetaldehyde) and
      radiation in concentrations and doses modeling the conditions in extended orbital
      mission].
AB  - The paper presents the results of an investigation with mice subjected to
      isolated and successive exposure to a blend of chemical agents (acetone, ethanol,
      acetaldehyde) at MPC levels defined for piloted space vehicles followed by
      fractionated gamma-irradiation by daily 1 cGy (30 cGy total). The selected
      chemicals are the primary contributors to total air contamination and present in
      the prioritized list of compounds to be monitored to ensure air quality on
      piloted space vehicles. Radiation levels were determined with allowance for mice
      radiosensitivity to simulate the actual absorbed dose accumulated by crewmembers
      of orbital mission of up to a year in duration (10 cGy). Based on the findings in
      the hematopoietic system and erythrocyte biochemistry, energy exchange and redox
      parameters, pre-irradiation exposure to chemical agents within the MPC limits
      accentuated radiosensitivity gravely and, therefore, made mouse organism less
      tolerant to radiation. It was shown that adaptation of the hematopoietic system
      calls forth activation and significant straining of regulatory mechanisms equally
      in opposing to a single factor or combination of chemical and radiation exposure.
      The marked tension of these mechanisms persisted till day 30 of recovery.

PMID- 22953537
TI  - [Neuromuscular status of children of different gestational age on the stage of
      transition from intrauterine immersion to the earth's gravity].
AB  - The work was aimed at describing the neuromuscular status of premature baby in
      the context of the ontogenetic and zero gravity model using the results of
      superficial interference electromyography (IEMG). Throughout six postnatal weeks,
      IEMG of premature babies is similar to EMG of full-term child on the first days
      of extrauterine life; IEMG is characterized by a "simplified" temporal structure,
      low amplitude and frequency, IEMG dynamics of fullterm child is slow in contrast
      to premature baby; the reason seems to be maximum long intrauterine life during
      which the motor system gets better prepared and maturates. On the other hand,
      complexity and high amplitude of premature baby IEMG as compared with full-term
      child of the same postconceptual age are associated with the inevitable sensory
      stimulation after birth. Abilitation procedures provided to premature baby could
      be adapted to the purposes of post-flight rehabilitation of cosmonauts.

PMID- 22953538
TI  - [Lipid peroxidation and the antioxidant defense system in hypergravity-exposed
      human].
AB  - Nine human subjects at the age of 25 to 45 participated in the studies of effects
      of the +G endurance limits: 8.30 +/- 0.30 +Gx (chest-back) and 6.51 +/- 0.28 +Gz
      (head-pelvis). Blood samples were collected 7 days prior to, in an hour and in 1
      and 7 days after centrifugation. Blood serum was analyzed for lipid peroxidation
      (LPO) products such as diene conjugates, malone dialdehyde, schiff bases, and
      also antioxidant defense system (AOS) components including tocopherol,
      glutathione peroxidase (GP) activity, catalase and total antioxidant activity.
      Exposure to +Gx and +Gz resulted equally in LPO inhibition. AOS activation was
      accounted for water-soluble GP and catalase; however, it should not be excluded
      that LPO intensity declined due to the trend of biomembranes phase state toward a
      greater viscosity. LPO inhibition was found more pronounced following exposure to
      +Gz but not +Gx.

PMID- 22953539
TI  - [Analysis of protein ratios based on the studies of human urine proteome in an
      experiment with 105-day isolation].
AB  - Purpose of the work was to study urine proteome of healthy human subjects during
      105-day isolation in controlled environment of the IBMP chamber with a self
      sustained life support system. The parameters under study were diurnal rhythm,
      physical activity, water intake, as well as consumption of sodium, protein and
      some other basic nutrients. Urine was sampled by 6 male subjects at the age of 25
      to 40 years admitted to the experiment by the medical certification commission.
      The studies were performed with the use of proteome data acquisition
      technologies; the cutting-edge bio-information analysis techniques including
      reconstruction of associative gene networks were applied to investigate the urine
      proteome profile, to structure experimental data in light of the existing
      physiological concepts and to formulate viable hypotheses for ensuing
      experimental verification. Proteins of different origin were identified in urine;
      appearance or disappearance of proteins was in tight correlation with salt
      consumption.

PMID- 22953540
TI  - [Calcium and phosphorus content of human organism during 105-day isolation].
AB  - Total and ultrafiltered calcium, total and inorganic phosphorus in blood serum
      and diurnal secretion of calcium and phosphorus with urine were determined before
      (baseline data collection) and on days 30, 60 and 105 of human subjects'
      isolation. Calcium and phosphorus content in hair was determined during BDC and
      on day 105 of the experiment. The measurements were fulfilled with the help of
      inductively coupled plasma atomic emission spectrometry. Levels of total and
      ultrafiltered calcium, total and inorganic phosphorus as well as urine calcium
      and phosphorus in daily urine and hair varied within admissible physiological
      ranges unfailingly at all the times of investigation. Shifts in the serum calcium
      and phosphorus balance occur at the expense of their physiologically active forms
      representing an immediate reaction to the experimental conditions. Calcium and
      phosphorus levels deviated from baseline values after 30 days of isolation and
      demonstrated stability till day 105.

PMID- 22953541
TI  - [Effects of different neuromediators and regulatory peptides on the impulse
      activity of inferior vestibular nucleus neurons].
AB  - Microelectrode techniques and microionophoresis of physiologically active
      substances were used in experiments with cats to show the ability of classic
      neuromediators (L-glutamate, L-aspartate, acetylcholine, noradrenaline, gamma
      aminobutyric acid (GABA), glycine and others) and regulatory peptides
      (enkephalines, TRH, substance P, vasoactive interstitial peptide (VIP),
      somatostatin (SS) and others) to influence directly the majority (60 to 100%) of
      neurons in the inferior vestibular nucleus (IVN). The inhibitory effect of
      enkephalines, VIP and SS on the neurons impulse activity was virtually
      uncompromised on the background of L-glutamate activity. In addition, it was
      stated that enkephalines, VIP and SS are potent to augment the inhibitory effect
      of GABA and glycine. Consequently, these substances have the capability to act as
      IVN neuromediators and/or neuromodulators.

PMID- 22953542
TI  - [Morphofunctional characteristics of rats' bone tissue after acute and subchronic
      emotional stress].
AB  - The investigation into the bone morphofunctional effects of acute and subchronic
      stress were performed in a series of two experiments with rats. In the first
      experiment, rats were subject to acute stress induced by confinement in plastic
      boxes for 1, 2.5 and 6 hours. In the other experiment, rats experienced
      subchronic stress from daily confinement for 5.5 hours during 3 and 9 days.
      Already after 2.5 hours in confinement the rats increased the number of
      trabecular osteoclasts and How-ship lacunas, as well as the blood level of free
      hydroxyproline. However, transformations of bone microarchitectonics, i.e. growth
      of trabecular breaks and sponger taper on femur X-ray pictures as an evidence of
      skeleton mechanic deterioration and relative femur mass reduction were found no
      earlier than after 9 days of stress

PMID- 22953543
TI  - [The optimization approach to arterial hemodynamics in the diastole phase].
AB  - The paper outlines the procedure and results of optimizing the arterial
      hemodynamics diastole phase. Mathematical relations for optimal diastolic
      pressure dynamics and length and arterial compliance coefficient were derived.

PMID- 22953544
TI  - [Holter monitoring of primates].
AB  - Validation of the Holter harness developed for cardiac monitoring of caged rhesus
      macaques attested to usability of the technique for studying the cardiac rhythm
      variability in primates.

PMID- 22953545
TI  - [Paroxysmal consciousness disorders among aviation personnel].
AB  - The results of studying paroxysmal consciousness disorders among aviation
      personnel are presented. Of 137 episodes documented over 10 years of observation,
      epileptic seizure was diagnosed in 28%, fainting in 57% and paroxysmal brain
      bioelectrical activity without loss of consciousness in 15% cases. Comprehensive
      analysis pinpointed clinical signs, instrumental findings, and major etiological
      factors provoking loss of consciousness paroxysms that include various somatic
      disorders, intoxication, cerebral injury, etc.

PMID- 22953546
TI  - [Manifestation of asymptomatic bacteremia in essentially healthy people].
AB  - To improve individual health evaluation, blood plasma samples of essentially
      healthy male and female citizens of Blagoveschensk (18 to 35 y/o) were analyzed
      under the scanning electron microscope. In 84.84% of samples, compound
      morphogenesis of elementary bodies, their conglomerates and daughter individuals
      matched the L-form bacteria. Dynamics of morphotypes detected in plasma mirrored
      the immunobiological state of organism, which can benefit to individual health
      monitoring.

PMID- 22953547
TI  - [Infallible reference points].

PMID- 22953548
TI  - Picking up the scent: Wave of practice acquisitions by hospitals has antitrust
      regulators on notice.
AB  - With the growing wave of acquisitions of practices by hospitals, antitrust
      regulators are putting the deals under harsh scrutiny to see if they're just a
      cover for raising prices rather than coordinating care and improving quality. "If
      there's an issue, I want to know about it now," says St. Luke's President and CEO
      Dr. David Pate, whose hospital met such a roadblock. "Let's just see if there are
      issues. We don't believe that there are."

PMID- 22953549
TI  - Higher-value performance: Checklist's 10 strategies aimed at improving quality,
      cutting costs.

PMID- 22953550
TI  - 'He loves a challenge': Highmark's new chief joins amid turmoil, effort to
      acquire West Penn.

PMID- 22953551
TI  - By the letter: Leapfrog's grading system draws mixed reactions from hospitals.

PMID- 22953552
TI  - Double target: Quality measures offer CMS' direction for improving dual
      eligibles' care.

PMID- 22953553
TI  - Something for everyone: For-profits could benefit from Illinois charity law.

PMID- 22953554
TI  - Bridging a gap: Support systems link docs with diagnoses: developers.

PMID- 22953555
TI  - Hungry for deals: But healthcare companies aren't spending as much.

PMID- 22953556
TI  - Divided we stand: With partisan polarization at a 25-year high, can we ever break
      the gridlock?

PMID- 22953557
TI  - A common thread: Altschuler sees IT as key to growth at Children's Hospital of
      Philadelphia.

PMID- 22953558
TI  - Seeing beyond the vision: Mercy's Britton champions IT and the change necessary
      to maximize its value.

PMID- 22953560
TI  - Foreign relations: U.S. providers enter variety of collaborations.

PMID- 22953559
TI  - High on the list: For Virtua's Miller, state-of-the-art IT a top priority across
      the board.

PMID- 22953561
TI  - You'll feel less rushed if you give time away.

PMID- 22953562
TI  - Bringing science to the art of strategy.
AB  - Many managers feel doomed to trade off the futile rigor of ordinary strategic
      planning for the hit-or-miss creativity of the alternatives. In fact, the two can
      be reconciled to produce novel but realistic strategies. The key is to recognize
      that conventional strategic planning, for all its analysis, is not actually
      scientific-it lacks the careful generation and testing of hypotheses that are at
      the heart of the scientific method. The authors outline a strategy-making process
      that combines rigor and creativity. A team begins by formulating options, or
      possibilities, and asks what must be true for each to succeed. Once it has listed
      all the conditions, it assesses their likelihood and thereby identifies the
      barriers to each choice. The team then tests the key barrier conditions to see
      which hold true. From here, choosing a strategy is simple: The group need only
      review the test results and choose the possibility with the fewest serious
      barriers. This is the path P&G took in the late 1990s, when it was looking to
      become a major global player in skin care. After testing the barrier conditions
      for several possibilities, it opted for a bold strategy that might never have
      surfaced in the traditional process: reinventing Olay as a prestigelike product
      also sold to mass consumers. The new Olay succeeded beyond expectations-showing
      what can happen when teams shift from asking "What is the right answer" and focus
      instead on figuring out "What are the right questions?".

PMID- 22953563
TI  - Can light-touch avoid Lansley avoid the toughest decisions?

PMID- 22953564
TI  - Lansley: Management cuts to slow after 2012.

PMID- 22953565
TI  - Pick on someone your own size.

PMID- 22953566
TI  - The realities of M&A.

PMID- 22953568
TI  - Acute future. Talking about failure.

PMID- 22953567
TI  - Our non-hierarchical future.

PMID- 22953569
TI  - Health and Social Care Act. From act to action.

PMID- 22953570
TI  - On image storage.

PMID- 22953571
TI  - Medical imaging. The bigger picture.

PMID- 22953572
TI  - Focus on the right thing.

PMID- 22953573
TI  - Collaborate and conquer.

PMID- 22953574
TI  - Whistleblowing. Culture shock.

PMID- 22953575
TI  - Data management. On storage systems.

PMID- 22953576
TI  - Data management. Lock up your data.

PMID- 22953577
TI  - Data management: case studies. Solving the storage problem.

PMID- 22953578
TI  - Service provision. To protect and serve.

PMID- 22953579
TI  - Service transformation. Soar with the high-flyers.

PMID- 22953580
TI  - Partnership working. Tips for being first among equals.

PMID- 22953581
TI  - Commissioning. Sit down and start saving.

PMID- 22953582
TI  - The social network.

PMID- 22953583
TI  - Pheidippides' last words: "My feet are killing me!".

PMID- 22953584
TI  - We get by with a little help from our friends.

PMID- 22953585
TI  - AMA sharpens focus; grows in membership.

PMID- 22953586
TI  - Rising medical education debt a mounting concern. Graduates also face less
      favorable repayment terms, shortage of training positions.

PMID- 22953587
TI  - Did the GOP shrug Ron Paul?

PMID- 22953589
TI  - Modern cardiothoracic surgery: current state-of-the-art & emerging technologies.

PMID- 22953590
TI  - Off-pump coronary artery bypass grafting.
AB  - Cardiovascular disease is the leading cause of death in the United States and
      most developed countries. The majority of deaths are due to coronary artery
      disease. It is estimated that 419,000 coronary artery bypass grafting (CABG)
      procedures were performed in the United States in 2009 for the surgical treatment
      of coronary artery disease. Off-pump CABG (without the use of cardiopulmonary
      bypass) is an attractive less invasive operative approach with multiple patient
      benefits.

PMID- 22953591
TI  - Surgical treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, resulting in
      significant morbidity and mortality, and enormous socio-economic consequences.
      Though many surgical procedures exist for the treatment ofAF, the Cox-Maze IV
      procedure developed at Washington University has shown excellent long-term
      results in diverse patient populations. Furthermore, advances in preoperative
      diagnostic technology currently under investigation at our institution may allow
      for further refinement and individualization of the surgical treatment ofAF in
      the future.

PMID- 22953592
TI  - New developments in the surgical management of end-stage heart failure.
AB  - Heart failure is a major healthcare problem associated with morbidity and
      mortality. Despite progress in treatments, the prognosis of heart failure remains
      poor. Standard treatments for heart failure include medical therapy,
      resynchronization therapy, and cardiac surgery. Heart failure teams providing
      guideline based care assist in the optimal management for advanced heart failure.
      Progression of heart failure despite optimal management may be treated with heart
      transplant. In non-transplant eligible patients, implantable left ventricular
      assist devices (LVADs) may improve patients 'quality of life and survival.
      Advances in LVADs, including smaller size, increased device durability, and
      (near) totally implantable devices, may enable LVADs to become an option in less
      sick patients. Evolving therapeutics such as stem cells and novel therapeutics
      may be combined with LVADs to allow myocardial recovery. This article will review
      current and developing strategies in the surgical management of heart failure
      with an emphasis on LVAD therapy.

PMID- 22953593
TI  - Indications for replacement of the thoracic aorta.
AB  - Thoracic aortic diseases that require surgical management include aneurysms of
      the root, ascending, arch or descending aorta; aortic dissections and
      thoracoabdominal aneurysms. These pathologic processes encompass acute and
      chronic presentations. Early detection is the key to positively affect survival.
      The final treatment for these pathologies is surgical but medical therapy can
      prevent disease progression and many times obviate the need for surgery. In this
      article, we review the most common thoracic aortic diseases and their management.

PMID- 22953594
TI  - Transcatheter aortic valve replacement.
AB  - Aortic stenosis is the most common form of valvular heart disease in the Western
      world and until recently, surgical aortic valve replacement has been the only
      treatment available for patients with this disease that has been shown to improve
      both symptoms and survival. Transcatheter aortic valve replacement has emerged as
      a new therapy for patients with severe aortic stenosis who are poor surgical
      candidates due to their elevated surgical risk. As longer follow up is obtained
      and improvements continue to be made in the current available prostheses,
      transcatheter aortic valve replacement will likely become a treatment alternative
      for high-risk patients with severe aortic stenosis.

PMID- 22953595
TI  - Robotic thoracic surgery: an evolution in progress for the treatment of lung
      cancer.
AB  - The field of robotic thoracic surgery has exploded in the last five years.
      Robotic technology allows the surgeon to perform complex operations with smaller
      incisions. As robotic systems become smaller, more efficient and the surgeons
      gain more experience, the results will continue to improve. The goal is less
      trauma to the patient which will decrease hospital stay, complications and lower
      health care costs, while allowing faster healing and productivity.

PMID- 22953597
TI  - The prevalence of dental caries in Missouri and its relation to systemic disease:
      opportunities for Missouri to improve the health of its citizens.
AB  - Recently, it has been recognized that poor oral health conditions, especially
      periodontitis, have been a contributing factor to several systemic diseases.
      Evidence shows that Missouri should be concerned about the current state of
      caries and its prevention. The prevalence of caries and lack of preventative care
      in Missouri warrants an examination of the current efforts in place to reduce
      caries and the creation of novel approaches that bridge the gap between oral and
      medical care. This paper discusses this problem in depth.

PMID- 22953596
TI  - Cardiovascular damage resulting from chronic excessive endurance exercise.
AB  - A daily routine of physical activity is highly beneficial in the prevention and
      treatment of many prevalent chronic diseases, especially of the cardiovascular
      (CV) system. However, chronic, excessive sustained endurance exercise may cause
      adverse structural remodeling of the heart and large arteries. An evolving body
      of data indicates that chronically training for and participating in extreme
      endurance competitions such as marathons, ultra-marathons, Iron-man distance
      triathlons, very long distance bicycle racing, etc., can cause transient acute
      volume overload of the atria and right ventricle, with transient reductions in
      right ventricular ejection fraction and elevations of cardiac biomarkers, all of
      which generally return to normal within seven to ten days. In veteran extreme
      endurance athletes, this recurrent myocardial injury and repair may eventually
      result in patchy myocardial fibrosis, particularly in the atria, interventricular
      septum and right ventricle, potentially creating a substrate for atrial and
      ventricular arrhythmias. Furthermore, chronic, excessive, sustained, high
      intensity endurance exercise may be associated with diastolic dysfunction, large
      artery wall stiffening and coronary artery calcification. Not all veteran extreme
      endurance athletes develop pathological remodeling, and indeed lifelong
      exercisers generally have low mortality rates and excellent functional capacity.
      The aim of this review is to discuss the emerging understanding of the cardiac
      pathophysiology of extreme endurance exercise, and make suggestions about
      healthier fitness patterns for promoting optimal CV health and longevity.

PMID- 22953598
TI  - New perspectives in the care of Parkinson disease.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder.
      Since the initial description of PD, clinical evaluation and management has
      focused on the motor signs and symptoms. Recent advances in our knowledge of
      neurologic involvement has led to a new emphasis on a broad spectrum of clinical
      features prompting the development of guidelines by the American Academy of
      Neurology for ongoing care of patients with PD. This review will touch on the
      historical aspects and traditional management of PD and discuss the latest
      recommendations for evaluation and care of PD patients. A broadened understanding
      of the multisystem nature of PD will enable physicians to improve the care and
      quality of life of their patients.

PMID- 22953599
TI  - Six steps to increasing case acceptance.

PMID- 22953600
TI  - Drug therapy for the pregnant dental patient.
AB  - Providing needed dental treatment, managing oral infection, and controlling pain
      are essential functions of dentists for helping patients maintain overall health
      during pregnancy. Medications commonly required for dental care consist of local
      anesthetics and associated vasoconstrictors, centrally and peripherally acting
      analgesics, sedative and anxiolytic agents, and antibiotics. Therapeutic drugs
      routinely used in dental practice are selected because of their known safety and
      effectiveness. However, for a pregnant patient requiring dental care, the agents
      routinely prescribed should be reevaluated for potential risks to the mother
      and/or fetus. The decision to administer a specific drug requires that the
      benefits outweigh the potential risks of the drug therapy. This article reviews
      and updates the recommendations for using dental therapeutic agents, thereby
      enabling general practitioners to select the safest drugs when treating pregnant
      dental patients.

PMID- 22953601
TI  - Caries detection using light-based diagnostic tools.
AB  - Modern caries treatment concepts like caries management by risk assessment-
      CAMBRA--entail diagnosing early caries lesions in a precavitated stage to make it
      possible to reverse the caries process with remineralization and bacteria
      reduction efforts. Newer, sensitive caries diagnostic tools can serve not only
      for early detection but also for monitoring of caries lesions to confirm the
      success of prevention and remineralization efforts. This article describes light
      based caries diagnostic tools, with emphasis on fluorescence-based techniques,
      and compares the most common available fluorescence-based tools with a
      standardized visual caries inspection system-the International Caries Detection
      and Assessment System (ICDAS II). Fluorescence tools that provide high-resolution
      fluorescence pictures are likely to provide more reliable scores than
      fluorescence devices that assess via a single spot. The better visibility of the
      high-resolution fluorescence imaging could prevent unnecessary operative
      interventions.

PMID- 22953602
TI  - Case involving CAD/CAM-generated, screw-retained bridge demonstrates dentistry's
      scientific progression.
AB  - The patient in the case presented had successfully used a maxillary overdenture
      for more than three decades. However, the time had come for the prosthetic
      appliance to be replaced. This case, which involved the use of a titanium
      understructure that was designed and fabricated using CAD/CAM technology,
      illustrates how far dentistry has come since the patient first presented to the
      clinician some 35 years ago when dental science had not yet included such
      innovations as bone grafting and CT scans.

PMID- 22953603
TI  - A systematic approach to recreate a patient's former smile.
AB  - In this case involving a 29-year-old woman with a history of stomach-acid-related
      reflux and extensive loss of tooth structure, the patient desired to regain the
      smile she "used to have." The treatment goals throughout the process were to
      manage risk, use minimally invasive procedures, and improve the prognosis in each
      of the four dental categories-periodontal, biomechanical, functional, and
      dentofacial. The treatment plan utilized a systematic approach to sequentially
      restore and protect the young woman's dentition. It included esthetic crown
      lengthening, establishing the ideal esthetic position of maxillary anterior and
      posterior teeth, addressing the mandibular plane of occlusion, and achieving
      optimal function.

PMID- 22953604
TI  - An era of evidence-based implant dentistry: 30 years since Toronto.

PMID- 22953605
TI  - BIOMET 3i: implant treatment to optimize restorative procedures.

PMID- 22953606
TI  - Glidewell's restorative-driven implant solutions: simple, convenient, affordable.

PMID- 22953607
TI  - Hiossen: helping educate clinicians with advanced implant courses.

PMID- 22953608
TI  - MIS implants: moving implantology forward.

PMID- 22953609
TI  - Sirona imaging: all-inclusive implant solution.

PMID- 22953610
TI  - Z-systems' metal-free zirconia implants high on biocompatibility, esthetics.

PMID- 22953611
TI  - Insuring influence: Annual ranking of healthcare's 100 Most Influential shows big
      impact of health coverage issues in America, from policy to business to politics.
AB  - It was a year of surprises on the 100 Most Influential People in Healthcare
      ranking, with the top three all being newcomers. The top 10 was dominated by
      players in government and the insurance business, spheres where reform is driving
      the agenda. "We are not waiting for reform to happen, we are leading the change,"
      says No. 2 Mark Bertolini, of Aetna.

PMID- 22953612
TI  - Home inspection: 500 practices launch Medicare project.

PMID- 22953613
TI  - Not playing by the rules: We broke tradition for this year's most influential
      person.

PMID- 22953614
TI  - MEasuring Nutrition risk in hospitalized patients: MENU, a hospital-based
      prevalence survey.
AB  - BACKGROUND: Depending on the definition used, malnutrition is prevalent among 20
      50% of hospitalized patients. Routine nutritional screening is necessary to
      identify patients with or at increased risk for malnutrition. The Nutrition Risk
      Screening (NRS 2002) has been recommended as an efficient tool to identify the
      risk of malnutrition in adult inpatients. OBJECTIVES: To utilize the NRS 2002 to
      estimate the prevalence of malnutrition among newly hospitalized adult patients,
      and to identify risk factors for malnutrition. METHODS: During a 5 week period,
      all adult patients newly admitted to all inpatient departments (except Maternity
      and Emergency) at Wolfson Medical Center, Holon, were screened using the NRS
      2002. An answer of "yes" recorded for any of the Step 1 questions triggered the
      Step 2 screen on which an age-adjusted total score > or = 3 indicated high
      malnutrition risk. RESULTS: Data were obtained from 504 newly hospitalized adult
      patients, of whom 159 (31.5%) were identified as being at high risk for
      malnutrition. Malnutrition was more prevalent in internal medicine than surgical
      departments: 38.6% vs. 19.1% (P < 0.001). Body mass index was within the normal
      range among subjects at high risk for malnutrition: 23.9 +/- 5.6 kg/m2 but
      significantly lower than in subjects at low malnutrition risk: 27.9 +/- 5.3 kg/m2
      (P < 0.001). Malnutrition risk did not differ by gender or smoking status, but
      subjects at high malnutrition risk were significantly older (73.3 +/- 16.2 vs.
      63.4 +/- 18.4 years, P < 0.001). Total protein, albumin, total cholesterol, low
      density lipoprotein-cholesterol, hemoglobin and % lymphocytes were all
      significantly lower, whereas urea, creatinine and % neutrophils were
      significantly higher in patients at high malnutrition risk. CONCLUSIONS: Use of
      the NRS 2002 identified a large proportion of newly hospitalized adults as being
      at high risk for malnutrition. These findings indicate the need to intervene on a
      system-wide level during hospitalization.

PMID- 22953615
TI  - Haemophilus influenzae activity in a single medical center in Israel in the post
      vaccine era.
AB  - BACKGROUND: The incidence of invasive disease due to Haemophilus influenzae has
      decreased since the implementation of vaccination against serotype B. OBJECTIVES:
      To describe the epidemiological, clinical and microbiological characteristics of
      patients with H. influenzae meningitis or bacteremia in the vaccine era in
      Israel. METHODS: We reviewed the medical records of all patients admitted to
      Shaare Zedek Medical Center between 1997 and 2010 who had blood or cerebrospinal
      fluid culture positive for H. influenzae. RESULTS: The study group comprised 104
      patients - 57 children and 47 adults. Overall, 21 (20%) of the infections were
      due to serotype b. The children had shorter hospitalizations (6vs. 12 days, P =
      0.005) and lower mortality rate (5% vs. 28%, P = 0.003) as compared to the
      adults. Bacteremic pneumonia was the most common diagnosis in adults (45% vs. 28%
      in children, P = 0.08) while meningitis was more common in children (17% vs.
      3.5%, P = 0.09). There was a seasonal pattern, with infections being more common
      during the winter and spring. CONCLUSIONS: Invasive H. influenzae disease is
      uncommon but still exists in both children and adults. The disease course tends
      to be more severe in adults. Even in the global vaccination era, serotype b
      constitutes a significant portion of invasive disease.

PMID- 22953616
TI  - Impact of a computerized integrated antibiotic authorization system.
AB  - BACKGROUND: Overuse and abuse of antibiotics is a major cause of microbial
      resistance. Within the hospital setting such overuse necessitates real-time
      supervision by infectious diseases (ID) specialists. OBJECTIVES: To evaluate the
      impact of a recently introduced computerized antibiotic authorization system on
      the pharmacy budget. METHODS: The study was performed in a 400 bed university
      hospital. With the new system, antibiotic requests are entered electronically by
      the ward physician and reviewed within minutes to hours by ID specialists. The
      feedbacks are seen in the wards and pharmacy. Successive years, one before and
      the other after introduction of the system, were compared. RESULTS: During the
      first year with the new system 7167 antibiotic requests were entered; 20% of them
      were rejected, mainly for improper indication (43% of the rejections). During
      that year the antibiotic expenditure was reduced by 17%, compared to the previous
      year (approximately equal to 200,000 US$), and was against the trend of the last
      5 years. Of the 35 antibiotics under the control of the ID team, the use of 7 was
      probably curtailed by the supervision. Pareto analysis revealed that four drugs
      constituted > 50% of the pharmacy's expenses. The mortality rate (per 1000
      hospitalization days) during those 2 years fell from 4.0 to 3.8. CONCLUSIONS:
      Computerized antibiotic control by ID specialists is a feasible cost-saving new
      modality that may help reduce unnecessary antibiotic prescriptions.

PMID- 22953617
TI  - Neonatal absolute nucleated red blood cell counts do not predict the development
      of cystic periventricular leukomalacia.
AB  - BACKGROUND: Infants with severe intraventricular-periventricular hemorrhage (IVH)
      have higher absolute nucleated red blood cell counts (aNRBC) at birth (a marker
      of intrauterine hypoxia) than controls. Periventricular leukomalacia (PVL) is
      known to be associated with prenatal and postnatal events. Whether PVL is also
      linked to intrauterine hypoxia is unknown. OBJECTIVES: To test the hypothesis
      that infants with PVL have higher aNRBC counts at birth than controls. METHODS:
      We studied 14 very low birth weight infants with PVL and compared them with 14
      pair-matched controls without PVL. Head ultrasound scans were performed in all
      infants on days 3-5 and 21-25 of life. Paired tests, Fisher exact tests and
      stepwise logistic regression were performed for analysis. RESULTS: The groups
      were similar for gestational age (GA), birth weight (BW), prolonged rupture of
      membranes (PROM), Apgar scores, IVH, and aNRBC counts. PVL correlated
      significantly with low partial pressure of CO2 (PCO2) and IVH (P < 0.01). In
      logistic regression, when GA, gender, PROM, antenatal steroid therapy, 1 (or 5)
      minute Apgar scores, IVH grade, nosocomial sepsis, patent ductus arteriosus,
      necrotizing enterocolitis (NEC), need for pressors, aNRBC counts and lowest PCO2
      were used as independent variables, PCO2 (P = 0.002), IVH grade (P= 0.001), GA (P
      = 0.038), NEC (P = 0.061) and use of dopamine (P = 0.010) remained in the
      analysis (total R2 = 68.2%). CONCLUSIONS: In contrast to severe IVH, aNRBC counts
      do not predict the development of PVL.

PMID- 22953618
TI  - The HLA-B*5101 molecule-binding capacity to antigens used in animal models of
      Behcet's disease: a bioinformatics study.
AB  - BACKGROUND: The human lymphocyte antigen (HLA) molecule B*5101 is a functioning
      receptor of the immune system and is generally accepted as a genetic marker for
      Behcet disease (BD), a multi-organ, chronic inflammatory disorder. The role of
      the HLA-B*5101 in the pathogenesis of BD is elusive. The assumption that HLA
      B*5101 has an active role in BD is suggestive, but no antigen has yet been
      identified. OBJECTIVES: To evaluate the potential binding capacity of various
      antigens to the HLA-B*5101 molecule. METHODS: Using bioinformatics programs, we
      studied the binding capacity of HLA-B*5101 and its corresponding rat molecule
      RT.A1 to the following antigens: heatshock protein-60 (HSP60), major
      histocompatibility complex class I chain-related gene A (MICA), retinal S-antigen
      (S-Ag), HLA-B27 molecule and its peptide (PD) and tropomyosin (TPM), all of which
      serve as antigens in animal models corresponding to BD. RESULTS: In each protein
      including the B*5101 molecule itself, the computerized programs revealed several
      short sequences with potential high binding capacity to HLA-B*5101 with the
      exception of B-27PD. The rat MHC RT1. Al. had no binding capacity to S-Ag.
      CONCLUSIONS: The evaluated proteins have the potential to bind to and to serve as
      potential antigens to the HLA-B*5101 and the rat MHC RT1.Al. molecules. The
      pathogenicity of these suggested short peptides should be evaluated in animal
      models of BD.

PMID- 22953619
TI  - Protein-energy malnutrition in hospitalized patients: early assessment for better
      outcome.

PMID- 22953620
TI  - Haemophilus influenzae: still a relevant invasive pathogen.

PMID- 22953621
TI  - Women's higher risk with N-6 PUFA vs. men's relative advantage: an "N-6 gender
      nutrition paradox" hypothesis.
AB  - The "Israeli Paradox" (1996) of low national health rankings despite adequate
      diet - attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) -
      coincided with long-observed dichotomies between women's worse international
      status vs. men's advantage. This raised the possibility of a gender link to high
      n-6 risk potentially explaining both national phenomena. Israeli women's
      disadvantage was shown by worse international rankings, i.e., life expectancy
      (LE)--11th vs. men's 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010);
      and all-cause and all-cancer mortality--both 15th vs. 2nd-best/22 (2000), and
      15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Cancer mortality rates for
      breast were 21.8% above vs. prostate 30.4% below Eur-A (27 country) averages
      (2005). Gender gaps/ ratios were smaller than European Union-15 averages, i.e.,
      for LE at birth by 34.4-26.4% (2000-2010), respectively, and at 65 years 45.9
      35.3%; all-cause mortality by 43.3-33.4%, and all-cancer 65.2-58.7%. The Israeli
      diet was mostly close to guidelines, but n-6 intake (10-12% kcal) was much higher
      than recommended and traditional "Mediterranean diet" levels. Research showing
      females' greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may
      suggest increased production of n-6 eicosanoids with known
      proinflammatory/oxidative/carcinogenic potential. An "Israeli N-6 Gender
      Nutrition Paradox" hypothesis is suggested here for the first time, associating
      women's higher risk and lead in the national "paradox" with greater potential for
      n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to
      men. This may also exacerbate women's risk associated with genetic predisposition
      (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional
      diets/foods together with increasing n-6 consumption and western disease rates
      emphasize the importance of considering gender nutrition in epidemiology and
      preventive strategies.

PMID- 22953622
TI  - The link between polycystic ovarian syndrome and type 2 diabetes: preventive and
      therapeutic approach in Israel.

PMID- 22953623
TI  - Atrial flutter in a post-transplant recipient.

PMID- 22953624
TI  - Multiple cavernomatosis presenting during pregnancy.

PMID- 22953625
TI  - Recurrent non-traumatic page kidney.

PMID- 22953626
TI  - Dabigatran in recurrent deep vein thrombosis: when one-size does not fit all.

PMID- 22953627
TI  - Severe Bordetella pertussis infection associated with hemolytic uremic syndrome.

PMID- 22953628
TI  - The Eighth International Congress on Autoimmunity.

PMID- 22953629
TI  - Removing financial barriers to medical treatment of alcohol dependence in Israel.

PMID- 22953630
TI  - The "mistress of healing eyes" in 15th century Spain.

PMID- 22953631
TI  - Antibacterial activity of bark of Alnus pendula against methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA)
      infections are a rapidly growing health problem around the globe. Recently, there
      has been considerable interest in the use of plant materials as an alternative
      method to control pathogenic microorganisms. In this study we evaluated the
      antibacterial activity of bark of Alnus pendula against MRSA. MATERIALS AND
      METHODS: The MIC determination was done using the microdilution broth method and
      bacterial growth was determined by measuring optical density using
      spectrophotometer. RESULTS: Alnus pendula bark EtOH extract and fractions (F-1, 
      2, -3 and -4) were investigated against MRSA. The most active fractions (F-3 and
      F-4) led to the isolation of oregonin (ORE) and hirsutanone (HIR). These
      compounds were active against MRSA strains with minimum inhibitory concentrations
      (MICs) ranging from 31.25 to 250 microg/ml MIC and 2 MIC of HIR completely
      inhibited the growth of MRSA. CONCLUSIONS: The bark EtOH extract of Alnus Pendula
      has potent antibacterial activity against MRSA.

PMID- 22953632
TI  - Effects of pinealectomy and exogenous melatonin on the brains, testes, duodena
      and stomachs of rats.
AB  - BACKGROUND: It is generally agreed that physiological levels of melatonin, a
      hormone secreted by the pineal gland, are important in protecting against
      oxidative stress-induced tissue damage. AIM: We investigated the effects that
      pinealectomy and the administration of exogenous melatonin have on the brains,
      testes, duodena and stomachs of rats. MATERIALS AND METHODS: Pinealectomized (Px)
      and sham-operated (non-Px) rats were used. We evaluated structural changes, and
      catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD) and
      malondialdehyde (MDA) levels. The rats were divided into the following five
      groups (eight rats in each group): sham (non-Px), Px+ vehicle, Px+ melatonin (10
      mg/kg given daily intraperitoneally for a week), melatonin and ethyl alcohol.
      RESULTS: The antioxidant levels in the tissue of Px rats were significantly lower
      than in those of the sham group. Administering melatonin significantly increased
      antioxidant levels (p < 0.05). The Px rats also showed a significant increase in
      MDA levels when compared to the sham group, and administering melatonin to the Px
      rats significantly reduced their MDA levels (p < 0.05). The severity of caspase-3
      staining was lower in the Px+ melatonin group than in the Px+vehicle group.
      CONCLUSIONS: These findings suggest that significantly more oxidative and
      structural changes occur in rats' brains, spinal cords and testes after
      pinealectomy, but that this can be diminished by melatonin treatment. However, Px
      does not have important effects on the duodenum and stomach.

PMID- 22953633
TI  - Protein-protein interaction network analysis of children atopic asthma.
AB  - BACKGROUND: Asthma prevalence has increased very considerably in recent decades
      such that it is now one of the commonest chronic disorders in the world. In this
      present study, We constructed a protein-protein interaction (PPI) network by
      mapped the differentially expressed genes (DEGs) to the PPI data and performed
      Gene Ontology (GO) enrichment analysis of the PPI network. We aimed to explore
      the pathogenesis of atopic asthma by bioinformatics methods. MATERIALS AND
      METHODS: To explore the pathogenesis of atopic asthma by bioinformatics methods,
      we obtained the global gene expression profile of pediatric asthmatic epithelium
      GSE18965 from Gene Expression Omnibus (GEO), and identified the differentially
      expressed genes between healthy nonatopic samples and atopic asthmatic samples
      RESULTS: Total 12 DEGs were selected. Furthermore, we constructed a protein
      protein interaction network by mapped the DEGs to the PPI data and performed Gene
      Ontology enrichment analysis of the PPI network. Total 15 GO terms were enriched
      and the enriched terms can be generally classified into two groups: cell cycle
      and immunity. CONCLUSIONS: Our results confirmed the role of cell proliferation
      and immune system in the pathogenesis of atopic asthma. Besides, our PPI network
      is useful in investigating the complex interacting mechanisms of transcription
      factors and their regulated genes in atopic asthma.

PMID- 22953634
TI  - A retrospective study comparing endovenous laser ablation and microwave ablation
      for great saphenous varicose veins.
AB  - BACKGROUND: Endo-venous laser or microwave ablation is a minimally invasive
      surgery for treating varicose veins of lower limbs. AIM: The aim of our study was
      to determine whether endovenous microwave ablation of the greater saphenous vein
      was associated with better effectiveness and less complications than the
      endovenous laser ablation. MATERIALS AND METHODS: From July 2008 to June 2011,
      259 cases (306 limbs) of varicose veins were assigned to endovenous laser
      ablation (n=138, 163 limbs) or endovenous microwave ablation (n=121, 143 limbs).
      RESULTS: Through analysis there was no significant difference of the operating
      time, length of hospital stay and Aberdeen score in the two groups. The
      recanalization rate was statistically higher in the laser group than that in the
      microwave group. The ecchymosis complication was significantly lower in microwave
      ablation than that of laser ablation group. However, the skin burn and paralysis
      complications were significantly lower in the laser ablation than that of
      microwave ablation group. CONCLUSIONS: Endo-venous microwave ablation is an
      effective alternative to laser ablation for treatment of varicose veins,
      associated with higher occlusion rate and without serious complications.

PMID- 22953635
TI  - Risk factors for progression of renal disease in patient with diabetic
      nephropathy.
AB  - AIM: The aim of this study was to investigate the annual rate of glomerular
      filtration rate (GFR) decline and associated risk factors with this decline in
      diabetic nephropathy patients. PATIENTS AND METHODS: A total of 122 type 2
      diabetes mellitus (DM) patients (66F, mean follow up time 39 +/- 19 months, mean
      age 56 +/- 10 years, mean duration of diabetes diagnosis 12.1 +/- 9.5 years)
      between 2003 and 2010 were evaluated retrospectively. Socio-demographic
      characteristics and blood pressure data, laboratory parameters, HbAlc, daily
      urine protein excretion both of the first and last visits of all patients were
      recorded. Patients were separated into three groups according to rate of GFR
      decline. Group 1 (n:35), group 2 (n:42) and group 3 (n:45) consisted of patients
      < 1 ml/dk/1.73 m2, 1-5 ml/dk/1.73 m2 and > 5 ml/dk/1.73 m2 annual rate of GFR
      decline respectively. Demographics, laboratory data and their treatments were
      compared in all three groups and were investigated factors that may influence the
      rate of GFR decline. RESULTS: The annual rate of GFR decline was 1.4 +/- 2.3
      ml/sec, -2.9 +/- 1.0 ml/sec and -11.9 +/- 9.1 ml/sec in group 1, 2 and 3
      respectively. Daily urine protein excretion was 0.9 +/- 1.3, 1.2 +/- 1.5 and 5.2
      +/- 5.5 g in groups respectively, was found significantly higher in group 3 (p <
      0.001). Serum albumin level was significantly lower in group 3 (p < 0.001). We
      found positive correlation between annual rate of GFR decline and last visit
      systolic blood pressure (SBP), daily proteinuria and parathormone levels (r:
      0.339, 0.447 and 0.289 p < 0.001, < 0.001 and 0.02 respectively) and negative
      correlation between GFR decline and deltaSBP (delta systolic blood pressure),
      pretreatment albumin, calcium and hemoglobin levels (r: -0.409, -0.526, -0.233
      and -0.467, p < 0.001, < 0.001, < 0.001 and 0.016 respectively). CONCLUSIONS:
      Proteinuria, hypoalbuminemia, anemia, and a change in SBP were found most
      effective in annual rate of GFR decline in patients with diabetic nephropathy.
      The early detection of these factors may slow the progression of nephropathy.

PMID- 22953636
TI  - Chronic constipation in hypercalcemic patients with primary hyperparathyroidism.
AB  - BACKGROUND: Chronic constipation (C), among gastrointestinal symptoms, is
      commonly associated with primary hyperparathyroidism (PHPT) and probably
      attributable to hypercalcemia. OBJECTIVE OF THE STUDY: To evaluate in patients
      affected with PHPT the prevalence of C utilizing a validated questionnaire and
      the current prevalence of C compared to that observed in the past and to evaluate
      the relationship between C and the severity of PHPT. METHODS: 55 outpatients
      affected with PHPT, admitted to our Department of Internal Medicine and Medical
      Specialities in the years (2006-2009) were studied (group 1: 50 postmenopausal
      women and 5 men, mean age 61.9 +/- 9.4 years), together with 55 sex and age
      matched controls (group 2). Also considered were a group of PHPT patients
      observed, in the same ambulatory, during the years '70-'80 (group 3). A
      questionnaire, Rome II criteria, was administered and used to define C, whereas
      only anamneses were used to define C in group 3. RESULTS: The prevalence of C in
      patients with PHPT was 21.8% in group 1 vs 12.7% in group 2 (n.s.) and 32.7% in
      group 3. There is a decreasing trend in the prevalence of C in patients with PHPT
      as observed from 1970-89 to 2006-2009 (p < 0.05). The reduction of C was
      associated together with a significant reduction in the serum calcium level (p <
      0.001). The presence of C vs its absence in patients with PHPT is characterized
      by higher values of calcemia (p < 0.001), ionized calcium (p < 0.001), and
      parathyroid hormone (p = 0.019). CONCLUSION: The actual prevalence of C in
      patients with PHPT is not significantly different from that found in the control
      group and is decreasing with respect to the past years. Moreover, C seems to be
      associated with the severity of the disease rather than with the diagnosis of
      PHPT per se.

PMID- 22953637
TI  - Anti-TNF alpha therapy in the management of extraintestinal manifestation of
      inflammatory bowel disease.
AB  - Inflammatory bowel disease, Crohn's disease and ulcerative colitis, are immune
      mediated disorders of unknown etiology that primarily affect the gastrointestinal
      tract. In addition, other organ systems can be involved such as joint/bones,
      skin, eyes, hepatobiliary tract, lungs and kidney. Overall, they represent
      extraintestinal manifestations of inflammatory bowel disease and may present
      before, in conjunction or after the onset of bowel disease. Extraintestinal
      manifestations are observed in 20-40% of patients and frequently have a negative
      impact on quality of patients' life. Some extraintestinal manifestations such as
      arthritis, erytema nodosum, pyoderma gangrenosum, iritis, uveitis have a
      pathogenic tumor necrosis factor alpha-dependent mechanism common with Crohn's
      disease and ulcerative colitis. Early recognition and treatment of
      extraintestinal manifestations can minimize potential severe complications. In
      this review we provide an overview on the prevalence and clinical aspects of the
      more commonly reported extraintestinal manifestations of Crohn's disease and
      ulcerative colitis and the role of tumor necrosis factor alpha inhibitors in
      their treatment.

PMID- 22953638
TI  - Prevalence and severity of sensorineural hearing loss in patients with
      exfoliation syndrome.
AB  - BACKGROUND AND OBJECTIVES: Exfoliation syndrome is characterized by the
      production and accumulation of abnormal extracellular material in many ocular and
      extraocular tissues. The aim of the present prospective case-control clinical
      study was to evaluate the effect of exfoliation syndrome on prevalence and
      severity of sensorineural hearing loss. MATERIALS AND METHODS: In the study
      participated 94 ears of patients with unilateral or bilateral ocular exfoliation
      syndrome (study group) and 44 ears of individuals without the syndrome (control
      group). Subjects with a history of conditions affecting hearing function and
      patients with conductive or mixed hearing loss, glaucoma or ocular hypertension
      were excluded from the study. All participants underwent pure-tone audiometry
      with air and bone conduction. During audiometry, the eventual sensorineural
      hearing loss and its severity was determined for each ear, at frequencies of 250,
      500, 1000, 2000, 4000 and 8000 Hz (Hertz). RESULTS: The mean age of participants
      was 74.7 years in both groups. Differences in age and gender distribution between
      the two groups were not statistically significant. Compared to control group,
      study group displayed: (1) Significantly higher prevalence rates of hearing loss
      at frequencies of 1000, 2000, 4000 and 8000 Hz (p = 0.007). (2) More severe
      hearing loss at frequencies of 4000 and 8000 Hz (p < 0.001). CONCLUSIONS: The
      above results demonstrate an effect of exfoliation syndrome on prevalence and
      severity of sensorineural hearing loss. These findings verify the theory that
      this syndrome is not only an ocular disease, but also a systemic disorder with
      potential otological complications.

PMID- 22953639
TI  - The association between schoolchildren intelligence and refractive error.
AB  - PURPOSE: The relationship between refractory errors and intelligence and the
      importance of genetic, regional and environmental factors in such associations,
      were investigated in a group of school children. SUBJECTS AND METHODS: One
      hundred and thirty-seven students (34.3% boys and 65.7% girls) from two primary
      schools were enrolled in the study. Cycloplegic refraction was performed and a
      spherical equivalent (SE) > or = 0.5D were determined as hyperopia; <-0.5D myopia
      and <1 cyl D astigmatism. Demographic factors, parent's education level, teacher
      based assessment of school performance and average score were also evaluated.
      RESULTS: Seventy-eight (56.9%) of subjects showed a form of refractory error;
      27%, 3% and 2.9% were myope, hyperope or astigmat, respectively, whereas 12.4% of
      them had both myopia and astigmatism and 10.2% showed hyperopia and astigmatism;
      43.1% were normal. CONCLUSIONS: Although our data revealed no distinction of
      average score between normal group and myopia, hyperopia, astigmatism or
      hyperopia-astigmatism, there is a statistically significant difference between
      normal group and those who had both myopia and astigmatism in which the later had
      a lower mediocre. Our results is somehow in contrast with other parallel studies
      demonstrating that positive connection between school performance and myopia can
      be explained by the geographical or racial discrepancies as well as subjects
      involved in the study and divergent set of cut off limits.

PMID- 22953640
TI  - 3D cone beam (CBCT) in evaluation of frontal recess: findings in youth
      population.
AB  - BACKGROUND: Frontal recess is the anatomical region most difficult to manage in
      endoscopic frontal sinus surgery due to the extreme variability of the cell
      patterns that may be observed in this area. CT has always been the gold standard
      in preoperative evaluation, but especially in the assessment of the causes of
      frontal recess obstruction and surgical failure. In recent years, this accredited
      and reliable method has been complemented by computed tomography cone beam
      (CBCT), which provides similarly detailed anatomical information with a lower
      dose of radiation. AIM: The purpose of this paper is to analyze and validate the
      use of CBCT in the study of frontal recess, and especially its anatomical
      variants in a youth population. MATERIALS AND METHODS: We analyzed 500 CBCT
      images of paranasal sinuses of young subjects with sinus inflammation pathology
      between 2009 and 2011. RESULTS: We observed that the method is very sensitive in
      detecting anterior and posterior recess cells, also in a youth population and
      then report on some significant images. CONCLUSIONS: We confirm the validity of
      CBCT, which by virtue of its sensitivity and specificity may be used in the
      analysis of frontal recess pathologies, especially when a young population is
      involved.

PMID- 22953641
TI  - Congenital cytomegalovirus infection: current strategies and future perspectives.
AB  - INTRODUCTION: Cytomegalovirus is the most common cause of congenital infections
      in humans and it produces considerable morbidity in newborns. AIMS: The present
      study reviews current concepts on epidemiology, clinical manifestations,
      diagnosis, treatment, future strategies and prognosis of children with congenital
      cytomegalovirus infection. RESULTS: Congenital cytomegalovirus infection can be
      symptomatic or not at birth, but about 10-20% of them all will exhibit
      neurological damage when followed up. Sensorineural hearing loss is the most
      frequent long-term consequence and is not manifest invariably at birth or in the
      neonatal period but in many cases becomes clinically apparent in later childhood.
      There are growing evidences that newborns with symptomatic congenital
      cytomegalovirus infection would benefit from treatment with either ganciclovir or
      valganciclovir, the most widely studied drugs in this setting. It is not yet
      clear if children with asymptomatic or pauci-symptomatic infection at birth would
      benefit from treatment. DISCUSSION: Studies evaluating treatment and long-term
      follow-up of infants with both symptomatic and asymptomatic infection are
      necessary, in order to definitely evaluate the short and long-term effectiveness
      and safety of both ganciclovir and valganciclovir and to identify risk factors
      associated to the development of long-term sequelae. In this way it will be
      possible to select those children that might benefit for treatment.

PMID- 22953642
TI  - Treatment approaches and outcomes in childhood supracondylar humerus fractures.
AB  - BACKGROUND: Being one of the most frequent elbow fractures during childhood,
      supracondylar humerus fractures require rapid diagnosis and treatment, as they
      may be associated with significant neurovascular and functional problems.
      QUESTIONS AND PURPOSES: To evaluate demographic and clinical features, and
      treatment outcomes of the patients with supracondylar humerus fractures who
      underwent open reduction+minimal osteosynthesis or closed reduction+percutaneous
      wiring. PATIENTS AND METHODS: Forty patients (30 boys + 10 girls) between 2 and
      13 years of age who were operated on with the diagnosis of supracondylar humerus
      fracture, between August 2003 and December 2006, were included. Open
      reduction+minimal osteosynthesis (n=34) and closed reduction+percutaneous wiring
      (n=6) were performed. The fractures were classified according to the Gartland
      classification and outcomes were assessed according to Flynn's criteria. RESULTS:
      All patients (mean age, 7.35 years; range, 2-13 years) had closed fractures (28
      left and 12 right). Seven (17.5%) and 33 (82.5%) patients had Gartland type II
      and III fractures respectively. Three patients had flexion-type and 37 patients
      had extension-type fractures. Based on Flynn's criteria, cosmetic results were
      excellent in 37 (92.5%) patients and good in 3 (7.5%) patients, and functional
      results were excellent in 36 (90%) patients, good in 3 (7.5%) patients, and poor
      in 1 (2.5%) patient. A surgical success rate of 97.5% was noted. No significant
      difference was found between wire configurations (p > 0.05). CONCLUSIONS:
      Treatment of supracondylar humerus fractures in children should be patient
      specific based on factors such as patient's age, soft tissue conditions and
      deformity status.

PMID- 22953643
TI  - Primary results of chest wall reconstruction with polydioxanone mesh on animals.
AB  - BACKGROUND: With the development of surgical techniques and biomedical material,
      increasing synthetic materials are applied to the chest wall reconstruction, such
      as autologous rib, muscle flap, bovine pericardium and sheet metal. AIM: To
      detect the safety and efficiency of synthetic material Polydioxanone (PDO) in
      chest wall reconstruction. MATERIALS AND METHODS: Healthy adult mongrel dogs
      operated with PDO, and then some clinical data were collected. RESULTS: Here we
      showed that PDO mesh could close down the function of chest wall defect, and PDO
      mesh could be degraded gradually and forms a fibrous layer with the surrounding
      tissues. Our data further demonstrated PDO mesh leads to slight lung adhesion
      with a small shrinkage. CONCLUSIONS: These findings thus provide the first
      evidence that the feasibility of PDO mesh in chest wall reconstruction in dogs.

PMID- 22953644
TI  - The frequency of MEFV gene mutation in patients admitted to hospital with
      preliminary diagnosis of familian mediterranean fever who undergone a prior
      appendectomy.
AB  - OBJECTIVES: Familial mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent and self-limiting fever, peritonitis, arthritis,
      synovitis, pleuritis, carditis, and erysipelas-like lesions. The aim of this
      study was to investigate the frequency of the MEFV gene mutation in patients who
      admitted to hospital with preliminary diagnosis FMF and who had undergone a prior
      appendectomy. PATIENTS AND METHODS: We retrospectively reviewed the files of 52
      patients between the ages of 7-18 who admitted to hospital with preliminary
      diagnosis of FMF and who had undergone a prior appendectomy. Age, gender and the
      MEFV gene mutations were included in the data. The 12 known, common MEFV gene
      mutations [E148Q, P369S, F479L, M6801 (G/C), M6801 (G/A), 1692del, M694V, M6941,
      K695R, V726A, A744S, R761H] were investigated in the patients. RESULTS: Of these
      52 cases, 29 (55.8%) were female and 23 (44.2%) were male. Their mean age was
      12.1 +/- 3.1 years (range 7-18 yr). MEFV gene mutation was detected in 31/52
      cases (59.6%). In this study was found an high frequency of the MEFV gene
      mutation in patients admitted to hospital with a preliminary diagnosis FMF who
      had undergone a prior appendectomy. MEFV gene mutations were M694V 16/41 (39%),
      E148Q 13/41 (31%), M6801 6/41 (15%), V726A 4/41 (10%) and R761H 2/41 (5%). Other
      genes mutations were F479L, M6801 (G/A), 1692del, M6941, K695R and A744S.
      CONCLUSION: There are too much indications of unnecessary appendectomy in MEFV
      gene mutation carriers. In MEFV gene mutation carriers the frequency of
      appendicitis can be higher than the normal population. A more detailed and
      extensive study should be done about it.

PMID- 22953645
TI  - Osteonecrosis of the jaws in patients assuming bisphosphonates and sunitinib: two
      case reports.
AB  - Osteonecrosis of the jaw (ONJ) is an unremitting adverse outcome associated with
      bisphosphonate therapy, primarily intravenously administered, in patients with
      bone metastases from solid tumors, multiple myeloma and osteometabolic diseases.
      From 2003 many cases of bisphosphonates related osteonecrosis of the jaw (BRONJ)
      have been reported in literature. Sunititnib is a novel anticancer agent used in
      gastrointestinal cancers and renal cancers resistant to imatinib. Recent reports
      describe the onset of ONJ in patients treated with both sunitinib and
      bisphosponates. A case of osteonecrosis of the jaw related to sunitinib, without
      association of bisphosphonate (BP) medications has been recently reported. A
      recent hypothesis suggests that antiangiogenic drugs such as sunitinib could
      cause ONJ even without the association with BPs. We describe a case of two
      patients affected by renal carcinoma under BP and sunitinib medication who
      developed stage III bisphosphonates-related osteonecrosis of the jaw (BRONJ).

PMID- 22953646
TI  - Clinical value of serum hepatocyte growth factor, B-cell lymphoma-2 and nitric
      oxide in primary breast cancer patients.
AB  - OBJECTIVES: The present study was undertaken to determine the clinical
      significance of serum levels of HGF, Bcl-2 and NO in the diagnosis and prognosis
      of breast cancer patients. PATIENTS AND METHODS: Forty four primary invasive
      breast cancer patients and fifteen health control subjects were enrolled in the
      present study. Serum HGF, Bcl-2 and No levels were assayed and correlated with
      clinico pathological parameters. ROS curve analysis was also done for each
      biochemical marker. RESULTS: The mean level of HGF was 1198.79 +/- 76.32 pg/ml
      versus 884.67 +/- 66.88 pg/ml for the control (p = 0.026). The HGF levels were
      significantly elevated in the patients with increasing the tumor stage (p =
      0.036). In addition, HGF levels were markedly increased in negative estrogen
      receptor patients (p = 0.039). The mean level of Bcl-2 in patients was 12.83 +/-
      1.97 ng/ml versus 5.09 +/- 0.40 ng/ml in control (p = 0.027). Levels of Bcl-2
      were elevated but not statistically significant in patients with grade I (GI)
      tumors, negative nodes, ER negative tumors and postmenopausal patients (p = 0.4,
      0.8, 0.7 and 0.5, respectively). The patients mean serum levels of NO were 63.07
      +/- 4.14 micromol/L versus 43.99 +/- 4.21 micromol/L in control (p = 0.014). The
      levels of NO were elevated but also not statistically significant in patients
      with tumor size I, GI tumors, ER negative tumors, positive nodes, stage II tumors
      and postmenopausal patients (p = 0.3, 0.6, 0.3, 0.7, 0.3 and 0.2 respectively).
      From the ROC curve analysis, it was observed that the area under curve for HGF,
      Bcl-2 and NO was 0.695, 0.842 and 0.711, respectively. This result indicates the
      good validity of the above biomarkers especially Bcl-2 to discriminate the ER
      positive from the negative tumors in primary breast cancer patients. CONCLUSION:
      This study demonstrates that the serum levels of HGF, Bcl-2 or NO may help in the
      diagnosis of breast cancer patients and may aid in disease prognosis. However,
      larger study with more patients are required.

PMID- 22953647
TI  - The role of oxidized regenerate cellulose to prevent cosmetic defects in
      oncoplastic breast surgery.
AB  - BACKGROUND: Breast conserving surgery (BCS) combined with postoperative
      radiotherapy has become the gold standard of locoregional treatment for the
      majority of patients with early-stage breast cancer, offering equivalent survival
      and improved body image and lifestyle scores as compared to mastectomy. In an
      attempt to optimize the oncologic safety and cosmetic results of BCS, oncoplastic
      procedures (OPP) have been introduced in recent years combining the best
      principles of surgical oncology with those of plastic surgery. However, even with
      the use of OPP, cosmetic outcomes may result unsatisfying when a large volume of
      parenchyma has to be removed, particularly in small-medium size breasts. AIM: The
      aim of this article is to report our preliminary results with the use of oxidized
      regenerate cellulose (ORC) (Tabotamp fibrillar, Johnson & Johnson; Ethicon, USA)
      as an agent to prevent cosmetic defects in patients undergoing OPP for breast
      cancer and to analyze the technical refinements that can enhance its efficacy in
      optimizing cosmetic defects. METHODS: Different OPP are selected based on the
      location and size of the tumor as well as volume and shape of the breast. After
      excision of the tumor, glandular flaps are created by dissection of the residual
      parenchyma from the pectoralis and serratus muscles and from the skin. After
      careful haemostasis, five layers of ORC are positioned on the pectoralis major in
      the residual cavity and covered by advancement of the glandular flaps. Two
      additional layers of ORC are positioned above the flaps and covered by cutaneous
      subcutaenous flaps. RESULTS: The use of ORC after OPP has shown promising
      preliminary results, indicating a good tolerability and positive effects on
      cosmesis. CONCLUSIONS: This simple and reliable surgical technique may allow not
      only to reduce the rate of post-operative bleeding and infection at the surgical
      site but also to improve cosmetic results.

PMID- 22953648
TI  - An unusual CT scan image.

PMID- 22953649
TI  - Traumatic forequarter amputation associated acute lung injury (ALI): report of
      one case.
AB  - One case of traumatic forequarter amputation associated acute lung injury (ALI)
      was presented. A discussion reviewing the treatment guidelines for this
      devastating injury, and pointing out the importance of supporting the lung and
      preventing the development of acute respiratory distress syndrome (ARDS) was
      included.

PMID- 22953650
TI  - A large calcified retroperitoneal extraskeletal osteosarcoma with consequent
      bilateral hydronephrosis.
AB  - Extraskeletal osteosarcoma (ESOS) is a rare malignant mesenchymal neoplasm that
      accounts for less than 4% of all osteosarcomas and approximately 1-2% of all soft
      tissue sarcomas. The tumor is typically located in the deep soft tissues, without
      attachment to skeletal bones. Although ESOS has been found todevelop virtually in
      every organ, its most common locations are the limbs. In the case of abdominal or
      pelvic lesions the diagnosis can be very difficult, thus it necessarily requires
      confirmation after exploratory laparotomy and histopathology. Such tumors may
      reach enormous sizes before detection because the enlarging mass may not be
      associated with pain. ESOS may be one of the differential diagnoses to be
      considered in the case of calcified masses arising in retroperitoneal space. Here
      we describe a bulky, bilateral, metastatic ESOS arising from the retroperitoneum
      and causing obstructive uropathy with consequent hydronephrosis.

PMID- 22953651
TI  - A case of psoriasis with secondary amyloidosis, associated symbrachydactyly of
      the hand and a transverse deficiency of the foot.
AB  - Secondary amyloidosis is associated with a variety of chronic inflammatory
      diseases such as rheumatoid arthritis, ankylosing spondylitis, familial
      Mediterranean fever, osteomyelitis, inflammatory bowel diseases and infective or
      neoplastic conditions. Few cases of secondary amyloidosis complicating psoriasis
      have been reported. We describe a 58-year-old patient with secondary amyloidosis,
      psoriasis, an associated symbrachydactyly of the hand and a transverse deficiency
      of the foot. To the best of our knowledge, no case of this association has been
      previously reported.

PMID- 22953652
TI  - Hereditary haemorragic teleangectasia and pregnancy: case report.
AB  - We report an uncommon case of a 38-years-old pregnant woman affected by HHT
      (Hereditary haemorrhagic telangiectasia; Osler-Weber-Rendu syndrome) who
      underwent to a caesarean section (CS) without any complication. The patient at
      36th weeks+1 day pregnancy referred to the Emergency Obstetric Unit due to a
      intercostals pain on left side. On third day after admission the woman started
      travailing and physicians decided to perform the CS. Considering that no AVMs was
      found at MRI, a continuous spinal anaesthesia was planned. On postpartum day 4
      the patient was discharged. This represents the only case published in the
      literature. Women with HHT, especially those with arteriovenous malformations
      (AVM), are at high risk in pregnancy due to physiological haemodynamic changes
      pregnancy associated. Early screening of patients with HHT for the presence of
      spinal cord or cerebral AVMs is recommended to optimise perioperative anaesthetic
      management and to avoid severe complications.

PMID- 22953653
TI  - Lipid emulsion in acute poisonings: still no convincing demonstration for its use
      in non-local anesthetic drug poisoning without life-threatening presentation.

PMID- 22953654
TI  - Transoral robotic cordectomy for early glottic carcinoma.
AB  - OBJECTIVES: We assessed the feasibility, safety, and efficacy of transoral
      cordectomy performed for early glottic cancer with the da Vinci Surgical System.
      METHODS: Subjects with early cancer of the vocal cords who were treated with
      transoral robot-assisted cordectomy were included for study. Data regarding the
      ability to perform robot-assisted resection, volume of blood loss,robotic
      operating time,pathological margin status, postoperative extubation,
      complications, length of hospitalization, duration until start of oral nutrition,
      and need for a tracheotomy were evaluated. RESULTS: Ten men with T1 glottic
      carcinoma underwent successful transoral robotic cordectomy with negative
      margins. The mean total robotic surgery time was 21.6 +/- 6.75 minutes (range, 10
      to 31 minutes). In all cases, the total blood loss was less than 20 mL. One
      subject needed a short-term tracheotomy and a nasogastric tube. The other 9
      subjects started oral nutrition 6 to 24 hours after operation. The mean duration
      of hospitalization was 4.1 +/- 2.23 days. CONCLUSIONS: Transoral robotic
      cordectomy with the da Vinci Surgical System was found to be feasible, relatively
      safe, and effective. The lower morbidity rate was an advantage of this method.
      Transoral robotic surgery provides better exposure, visualization, and access
      than does transoral laser microsurgery. Cordectomy with transoral robotic surgery
      should be an alternative to external-approach cordectomy and transoral laser
      microsurgery.

PMID- 22953655
TI  - Endoscopic treatment of adversely located osteomas of the frontal sinus.
AB  - OBJECTIVES: We assess the utility and limitations of an endoscopic technique in
      the treatment of osteomas that are considered difficult to manage endoscopically,
      ie, those located superiorly or laterally in the frontal sinus, extending beyond
      a virtual plane through the lamina papyracea, and we describe the principles of a
      surgical technique that facilitates removal of such tumors. METHODS: We performed
      a retrospective study on 8 patients with symptomatic frontal sinus osteomas,
      including tumors extending past the commonly recognized limits of endoscopic
      resection because of their size or site of attachment. RESULTS: All tumors were
      removed by a purely transnasal endoscopic approach. No major complications were
      observed during or after the operation. All patients experienced improvement or
      total regression of their symptoms. CONCLUSIONS: With appropriate instruments and
      specific endoscopic techniques, it is possible to resect osteomas that not long
      ago were deemed inaccessible to endoscopic surgeons. The commonly recognized
      limits of endoscopic treatment of such tumors may be exceeded in some cases;
      however, favorable anatomic conditions are decisive for a successful operation.

PMID- 22953656
TI  - Primary sclerosing paraganglioma of the thyroid gland: a case report.
AB  - OBJECTIVES: Paragangliomas are neuroendocrine tumors derived from extra-adrenal
      paraganglionic cells of the autonomic nervous system. Paragangliomas of the
      thyroid are rare, with only 28 cases reported in the literature. The sclerosing
      paraganglioma variant, characterized by marked stromal sclerosis and
      hyalinization, has scarcely been reported. METHODS: A 36-year-old woman with a
      history of a 1-cm vagal schwannoma followed with serial magnetic resonance
      imaging presented with a new solitary 2.5-cm enhancing soft tissue mass in the
      left thyroid. RESULTS: Ultrasound examination of the thyroid revealed a
      hypoechoic, hypervascular, malignant-appearing mass. Two fine-needle aspirations
      were insufficient for diagnosis, and the mass was deemed a lesion of undetermined
      significance with subsequent indeterminate molecular testing. A diagnostic left
      thyroid lobectomy was performed, and pathologic examination revealed a lesion
      consistent with a sclerosing paraganglioma. CONCLUSIONS: Sclerosing
      paragangliomas are rare tumors, and only 1 case involving a primary thyroid mass
      has been reported in the literature. Although the sclerosing variant has features
      suggestive of malignancy, the true incidence of malignancy is unknown, given the
      rarity of its presentation. However, given the overall benign nature of
      paragangliomas, the sclerosing variant is also likely benign, despite its
      malignant features on ultrasound and histopathologic examination.

PMID- 22953657
TI  - Serious complications during aural impression-taking for hearing aids: a case
      report and review of the literature.
AB  - OBJECTIVES: Complications during aural impression-taking for hearing aids are
      relatively rare. We present a case to highlight the need for vigilance when
      taking an aural impression and review the literature to identify other cases in
      order to assess the range of complications encountered and the sequelae of this
      potentially serious problem. METHODS: We present a case report and a review of
      the literature. RESULTS: The most common complication was the entry of mold
      material into the middle ear cavity. This frequently occurred in patients with a
      preexisting perforation of the tympanic membrane, although traumatic perforation
      occurred in 5 cases. Spread of the mold material within the middle ear cavity was
      frequently extensive, with 46% of cases involving the eustachian tube. There were
      6 cases of ossicular chain involvement: encasement of the ossicles in 5 and
      extensive ossicular erosion in 1. The extent of the surgical procedures performed
      varied widely, ranging from simple removal of the foreign body in the mastoid
      cavity to tympanomastoidectomy with a facial recess approach and ossiculoplasty.
      In 50% of cases, the patient recovered without any complication. However, further
      hearing loss was observed in 36% of cases. CONCLUSIONS: When mold material is
      impacted in the ear canal and visualization of the middle ear is obscured, we
      advise against simple piecemeal removal. Such cases are best managed by an
      experienced otologist.

PMID- 22953658
TI  - Bilateral duplicated internal carotid arteries presenting as middle ear masses: a
      case report and review of the literature.
AB  - OBJECTIVES: We seek to describe an individual with bilateral duplicated internal
      carotid arteries (ICAs) presenting as middle ear masses, to discuss the anatomy
      and characteristic imaging findings associated with this condition, and to
      familiarize clinicians with effective methods to prevent and manage complications
      related to this entity. METHODS: The clinical presentation of an individual with
      this unusual vascular anomaly was reviewed. A literature search was then
      performed to identify previously reported studies describing aberrant ICAs in
      order to characterize the presentation, anatomy, imaging findings, and management
      of this condition. RESULTS: An aberrant ICA presenting as a middle ear mass is
      uncommon; there are only approximately 45 reported cases to date. The majority of
      these cases presented as a unilateral anomaly without a duplication, were
      associated with pulsatile tinnitus and hearing loss, and were diagnosed during
      middle ear procedures. Bilateral aberrant ICAs are exceedingly rare, with only 14
      existing reports. Only 1 of these cases presented with duplicated ICAs. Our
      report demonstrates an unusual presentation of aberrant ICAs, as pulsatile
      tinnitus was absent and previous middle ear surgery had been performed without
      establishing this diagnosis and without any resulting complications. Furthermore,
      this case represents the first known instance of a bilateral duplicated ICA
      system without persistent stapedial arteries. Although vascular middle ear
      anomalies are unusual, complications of surgical manipulation have been
      documented. CONCLUSIONS: The clinician must have a high index of suspicion for
      vascular lesions in patients presenting with a retrotympanic mass. Appropriate
      diagnostic imaging studies should be performed to exclude this diagnosis before
      middle ear exploration. Should injury to the carotid artery occur, surgeons
      should follow specific guidelines to avoid potentially serious complications.

PMID- 22953659
TI  - Normalization of temporal aspects of swallowing physiology after the McNeill
      dysphagia therapy program.
AB  - OBJECTIVES: We examined the timing of physiological swallowing events in patients
      before and after completion of an exercise-based dysphagia intervention (McNeill
      Dysphagia Therapy Program; MDTP) and compared their performance to that of
      healthy volunteers. METHODS: Eight adults (mean age, 57.5 years) with chronic
      dysphagia (mean, 45 months) completed 3 weeks of the MDTP. Before and after the
      MDTP we measured lingual-palatal and pharyngeal manometric pressures during
      swallows of thin liquid, thick liquid, and pudding material in 5-mL volumes.
      Using the pressure peak of the pharyngoesophageal segment clearing wave as the
      anchor point, we measured the relative timing of pressure peaks from the
      anterior, middle, and posterior parts of the tongue and the manometric peaks from
      the base of the tongue, the hypopharynx, and the nadir of the pharyngoesophageal
      segment. We compared these results to identical measures obtained from 34 healthy
      adults (mean age, 44.0 years). RESULTS: The timing of physiological events before
      the MDTP was significantly slower than that of the group of healthy volunteers.
      The timing data from after the MDTP were not significantly different from those
      of the healthy group. The magnitude change was greatest for thin liquid.
      CONCLUSIONS: Dysphagia therapy with the MDTP improves the timing of physiological
      events during swallowing. Temporal coordination of swallowing components after
      therapy approximates that of healthy adults, suggesting a normalization of
      swallow timing after the MDTP.

PMID- 22953660
TI  - The ram sign: detecting previously undiagnosed congenital laryngeal clefts in
      adults.
AB  - OBJECTIVES: We present the clinical characteristics of a case series of adult
      patients with type III laryngeal clefts according to the classification of
      Benjamin and Inglis, in an attempt to make practitioners aware of the "ram sign,"
      a clinical finding associated with laryngeal clefts in adults. Laryngeal clefts
      are uncommon defects that are nearly universally identified during infancy as a
      result of persistent aspiration and pneumonia. Undiagnosed laryngeal clefts in
      adults are extremely rare. METHODS: Three type III laryngeal clefts were
      identified in adults (29, 48, and 60 years of age) from one clinic over an 18
      month period. The existing literature features only one type III cleft, to our
      knowledge. The 60-year-old patient represents the oldest person in the English
      language literature to have a newly diagnosed laryngeal cleft. All three cases
      presented with various degrees of aspiration over an extended period. RESULTS:
      The computed tomographic imaging and endoscopic findings from these three
      patients were reviewed. The videolaryngoscopic images demonstrated that the "ram
      sign"--an endoscopic finding associated with redundant soft tissue overlying the
      arytenoid cartilages that prolapses into the cleft, creating the appearance of
      ram's horns--was a consistent and striking feature in all three patients.
      CONCLUSIONS: Although rare, laryngeal clefts may represent an underdiagnosed
      entity in the adult population. With increased awareness, they may be identified
      more frequently as a treatable cause of aspiration and recurrent pneumonia.

PMID- 22953661
TI  - Spectral- and cepstral-based acoustic features of dysphonic, strained voice
      quality.
AB  - OBJECTIVES: We sought to determine whether spectral- and cepstral-based acoustic
      measures were effective in distinguishing dysphonic-strained voice quality from
      normal voice quality and whether these measures were related to auditory
      perceptual ratings of strain severity. METHODS: Voice samples from 23 speakers
      with dysphonia characterized predominantly by strained voice quality and 23
      speakers with normal voice were acoustically analyzed. Measures related to the
      prominence of the cepstral peak and the ratio of low- to high-frequency spectral
      energies, as well as the variation of each, were computed from continuous speech
      and a sustained vowel. Correlations to perceptually rated strain severity were
      determined. RESULTS: Measures related to the cepstrum were the strongest
      discriminators between dysphonic-strained voice and normal voice. Variation in
      the ratio of low- to high-frequency spectral energies also significantly
      differentiated the two speaker groups. All measures were significantly correlated
      with perceptually rated strain severity, including an acoustic severity index
      that incorporated both cepstral- and spectral-based measures. CONCLUSIONS:
      Cepstral- and spectral-based measures that have been previously studied in
      dysphonia characterized by breathiness and roughness are effective in
      distinguishing strained dysphonia from normal voice quality. The utility of these
      acoustic measures is supported by their moderate-to-high relationship with
      perceptually rated strain severity.

PMID- 22953662
TI  - Ethnic disparity in skin complications following bone-anchored hearing aid
      implantation.
AB  - OBJECTIVES: Sound processor loading after implantation of a bone-anchored hearing
      aid is often delayed by skin-site complications. This study examined the
      frequency of skin-site complications in various ethnic groups and determined
      factors that may lead to higher rates of skin-site complications resulting in
      delayed processor loading. METHODS: Adult, English-speaking patients who
      underwent implantation of a bone-anchored hearing aid between 2007 and 2010 were
      reviewed. Demographic data including ethnicity, tobacco use, diabetes mellitus,
      immunosuppression, and long-term steroid use were determined. Major and minor
      skin-site complications and the time to processor loading were recorded. RESULTS:
      The mean time to processor loading was 9.5 weeks, and the mean follow-up time was
      23 months. There were no cases of osseointegration failure. African American
      patients had a significantly higher rate of major skin-site complications (p <
      0.005) and a longer time to processor loading (mean, 17.6 weeks; p < 0.05) than
      the other ethnic groups. There was no significant difference in minor skin
      complication rates. There was no correlation between diabetes mellitus, long-term
      immunosuppression, or tobacco use and skin-site complications. CONCLUSIONS: Skin
      complications can delay processor loading following implantation of a bone
      anchored hearing aid. There is a higher rate of major skin-site complications in
      African American patients, and these often delay processor loading. The risk of
      skin-site complications is not correlated with smoking, diabetes mellitus, or
      immunosuppression. An increased risk of skin-site complications is an important
      consideration for preoperative counseling.

PMID- 22953663
TI  - Adjuvant chemotherapy with an oral fluoropyrimidine, S-1, following reduced
      RADPLAT in advanced laryngeal cancer.
AB  - OBJECTIVES: Radiation Therapy Oncology Group study 91-11 found that in resectable
      advanced laryngeal cancer, the locoregional control rate achieved with reduced
      intra-arterial cisplatin and concurrent radiotherapy (RADPLAT) was comparable to
      that of a concurrent chemoradiotherapy arm, with reduced toxicities. However,
      distant metastases were more frequent. Our study retrospectively evaluated the
      efficacy and feasibility of adjuvant chemotherapy with S-1, an oral
      fluoropyrimidine, for distant metastases following reduced RADPLAT. METHODS: We
      analyzed 61 patients who were treated with reduced RADPLAT and achieved a
      complete response at the primary site. After the use of reduced RADPLAT, 24
      patients were administered S-1 for 2 weeks followed by 1 week of rest, and the
      cycle was repeated for 6 months (S-1+ group). Thirty-seven patients were not
      administered S-1 (S-1-group). RESULTS: The hazard ratio for distant metastases in
      the S-1+ group was 0.114 (95% confidence interval, 0.015 to 0.881; p = 0.0374).
      There was a significant difference in disease-free survival in favor of the S-1+
      group (p = 0.0455). Nineteen patients (79.2%) in the S-1+ group received S-1
      according to the planned schedule and dose. Grade 3 toxicities were observed in 2
      patients (8.3%), but there was no grade 4 event. CONCLUSIONS: In resectable
      advanced laryngeal cancer, S-1 adjuvant chemotherapy is an effective and feasible
      treatment option to control distant metastases following reduced RADPLAT.

PMID- 22953664
TI  - Mitral valve prolapse with left atrial enlargement out of proportion to mitral
      regurgitation.
AB  - Chronic severe mitral regurgitation (MR) is associated with compensatory dilation
      of the left atrium (LA) and left ventricle (LV). However, LA enlargement is not
      unique to patients with MR. Herein are reported the details of nine patients with
      mitral valve prolapse (MVP) and no more than mild MR, but in whom the LA
      enlargement is out of proportion to the MR severity. Because of the potential to
      overestimate MR severity using an integrative echocardiography/Doppler approach
      that includes evidence of chamber dilation in the diagnosis of severe MR, there
      may be significant clinical implications if the connective tissue abnormality
      underlying MVP or other factors results in an independent enlargement of the left
      atrium.

PMID- 22953665
TI  - Animal models of mitral regurgitation induced by mitral valve chordae tendineae
      rupture.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is a common valvular
      disease throughout the world. Various diagnostic techniques have been developed
      to assess the causes and severity of MR, and the therapeutic approaches to this
      disease have been widely documented. However, treatments for chronic MR remain
      controversial, and various animal models of chronic MR (including chordae
      tendineae rupture, rapid pacing and ischemia) have been developed to study the
      pathophysiology and therapeutic approaches to this condition. The study aim was
      to review the animal MR models that have been developed using a mitral valve
      chordae tendineae rupture technique. METHODS AND RESULTS: Among the animals used
      for these investigations, dogs and sheep have been most commonly used as models
      of MR induced by mitral valve chordae tendineae rupture, mainly due to
      considerations of cardiac size. Chordae tendineae cutting is performed using
      either closed- or open-chest techniques. In the closed-chest model, long flexible
      grasping forceps are positioned percutaneously in order to tear the mitral valve
      chordae. In the open-chest model, cardiopulmonary bypass is performed, and either
      selected chordae are cut under direct visualization or a non-specified number of
      chordae are cut, using a metal device inserted through the left ventricular apex.
      Whichever model is used, MR has been found to become chronic at three to six
      months after the induction of MR by chordae rupture. The reported mortality and
      complication rates of these models are high. CONCLUSION: In the long term, the
      experimental evolution of chronic MR is similar to the evolution occurring
      naturally in patients suffering from the condition. Hence, these models could be
      useful in understanding the disease better, and in testing new therapeutic
      modalities. The present review summarizes the physiological effects of each of
      these techniques, and compares the advantages and disadvantages of each
      procedure.

PMID- 22953666
TI  - Rheumatic mitral repair versus replacement in a threshold country: the impact of
      commissural fusion.
AB  - BACKGROUND AND AIM OF THE STUDY: In developing countries rheumatic heart disease
      is the predominant indication for cardiac surgery. As the disease tends to
      progress, reoperation rates for mitral valve repairs are high. Against this
      background, the predictors of failure were assessed and the overall performance
      of repairs compared with replacements in a 10-year cohort of rheumatic single
      mitral valve procedures. METHODS: Between 2000 and 2010, a total of 646
      consecutive adult (aged >15 years) patients underwent primary, single mitral
      valve procedures. All 87 percutaneous balloon valvuloplasties (100%) were
      rheumatic, compared to 280 of the 345 primary mitral valve replacements (81%) and
      69 of the 215 primary mitral valve repairs (32%). As the study aim was to compare
      the outcome of mitral valve repair versus replacement in rheumatic patients of a
      threshold country, all 69 repair patients were propensity-matched with 69 of the
      replacement patients. Based on propensity score analysis, Kaplan-Meier actuarial
      analysis with log-rank testing was used to evaluate survival and morbidity.
      RESULTS: The follow up was 100% complete (n = 138), and ranged from 0.6 to 132
      months (mean 53.3 +/- 36.5 months). Actuarial freedom from valve-related
      mortality was 96 +/- 3% and 92 +/- 4% at five years, and 96 +/- 3% and 80 +/- 11%
      at 10 years for repairs and replacements, respectively (p = NS). Actuarial
      freedom from all valve-related events (deaths, reoperations and morbidity) was 80
      +/- 6% and 86 +/- 5% at five years, and 70 +/- 8% and 69 +/- 11% at 10 years (p =
      NS). Actuarial freedom from all valve-related events was 57 +/- 11% and 96 +/- 3%
      at five years (p = 0.0008), and 42 +/- 12% and 96 +/- 3% at 10 years (p < 0.001)
      for those mitral valve repairs with and without commissural fusion, respectively
      (p = 0.0002 overall). CONCLUSION: The long-term results for mitral valve
      replacement in an indigent, rheumatic heart disease population of a developing
      country were better than generally perceived. Notwithstanding, mitral valve
      repair has a superior long-term outcome in those patients who do not show
      commissural fusion at operation.

PMID- 22953667
TI  - Structural changes of rat mitral valve chordae tendineae during postnatal
      development.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve chordae tendineae are an essential
      component for correct functioning of the human heart. The microstructural make-up
      of the chordae is responsible for their tensile properties, and is seen gradually
      to change with age. However, little is known of the maturation of chordae
      tendineae and their microstructure. METHODS: To examine such maturation,
      structural changes in chordae tendineae were studied in rats at 1, 3, 7, 15 and
      30 days of postnatal life, and in adult rats. Differences in the chordae
      microstructure of each age group were observed using light microscopy. The
      collagen fibril crimp period was determined using polarized light microscopy.
      RESULTS: At day 1 after birth the chordae had yet to develop, and the lateral
      sides of the mitral valve leaflets were completely attached to the papillary
      muscles. Chordae developed through the formation of gaps in the leaflet tissue.
      From day 7 on, numerous chordae were seen. As the chordae matured, crimped
      collagen fibrils were formed and began to align in a longitudinally packed core
      with increasing density. The collagen fibril crimp period increased significantly
      with the age of the animal. CONCLUSION: Rat chordae tendineae have yet to develop
      at postnatal day 1. Morphological development and microstructural maturation of
      the chordae are not completed until adulthood (>30 days). A further understanding
      of the development of mitral valve chordae tendineae will provide insight for the
      use of tissue-engineered chordae in surgical repair.

PMID- 22953668
TI  - Recurrent mitral regurgitation due to ruptured artificial chordae: case report
      and review of the literature.
AB  - The use of expanded polytetrafluoroethylene (ePTFE) sutures has become an
      established method to correct mitral regurgitation due to elongated or ruptured
      mitral chordae. Mitral valve repair using artificial chordae has demonstrated
      excellent long-term results, particularly as ePTFE retains its flexibility with
      time and is highly resistant to mechanical stress. On conducting a literature
      review, four cases were found of recurrent mitral regurgitation due to the late
      (6-14 years postoperatively) rupture of ePTFE chordae. Herein, the case is
      described of artificial chordal rupture that required reoperation at 11 years
      after the initial mitral valve repair. In all previously reported cases, chordal
      rupture was related to the calcification of ePTFE, whereas in the present case
      only minimal calcification was observed at histology, and chordal rupture was
      most likely due to ePTFE fatigue-induced lesion. Although rare, rupture of the
      artificial chordae may cause recurrent mitral regurgitation; hence, the
      continuous monitoring of these patients, especially when the follow up extends
      beyond 10 years, appears mandatory.

PMID- 22953669
TI  - Repair of disrupted mitral annuloplasty following blunt chest trauma.
AB  - Traumatic mitral valve injury is rare, and few data exist regarding the impact of
      trauma on a previously repaired mitral valve. The case is presented of a dehisced
      mitral annuloplasty caused by a motor vehicle accident. The patient underwent
      successful re-repair of the mitral valve repair.

PMID- 22953670
TI  - Undersized annuloplasty for functional mitral regurgitation: is it responsible
      for clinically relevant mitral stenosis during exercise?
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess if an undersized
      mitral annuloplasty for functional mitral regurgitation (FMR) in dilated
      cardiomyopathy can determine a clinically relevant mitral stenosis during
      exercise. METHODS: Both, rest and stress echocardiography were performed in 12
      patients submitted to an undersized ring annuloplasty for FMR in dilated
      cardiomyopathy. The mean ring size was 27 +/- 1.3 mm. All patients were in NYHA
      functional classes I-II, were in stable sinus rhythm, and without significant
      residual mitral regurgitation (grade < or = 2/4). RESULTS: At peak exercise (mean
      81 +/- 12 W), the main cardiac performance indices were significantly improved,
      including systolic blood pressure (121 +/- 5.6 versus 169 +/- 14 mmHg, p <
      0.001), stroke volume (63 +/- 15 versus 77 +/- 14 ml, p < 0.001), left
      ventricular ejection fraction (43 +/- 9% versus 47 +/- 9%, p = 0.001), and
      systolic right ventricular function (pulsed tissue Doppler index peak systolic
      velocity: 8.6 +/- 1.7 versus 11.1 +/- 3.2 cm/s, p = 0.004). A mild increase in
      planimetric mitral valve area was observed at peak exercise (2.12 +/- 0.4 versus
      2.17 +/- 0.3 cm2, p = 0.05). Although the transmitral mean gradient was increased
      from 3.2 +/- 1.2 to 6.3 +/- 2.3 mmHg (p < 0.0001), the systolic pulmonary artery
      pressure did not change significantly (27 +/- 2.8 versus 30.1 +/- 6.4 mmHg, p =
      0.3), thus revealing a preserved cardiac adaptation to exercise. CONCLUSION: In
      these preliminary data, postoperative clinically relevant mitral stenosis was not
      observed in patients submitted to mitral repair for FMR. Stress echocardiography
      represents a valuable tool to assess an appropriate cardiac response to exercise
      and to detect a significant exercise-induced pulmonary hypertension after
      undersized annuloplasty ring surgery.

PMID- 22953671
TI  - Progression of aortic valve stenosis in adults: a systematic review.
AB  - BACKGROUND AND AIM OF THE STUDY: Published reports on the progression of aortic
      valve stenosis (AS) over time are usually small, with widely varying AS
      progression rate estimates. Reliable estimates of AS progression are important
      for surveillance scheduling and optimal timing of surgical or interventional
      treatment. This systematic review presents an overview of published evidence on
      AS progression over time in adult patients with AS. METHODS: A systematic review
      using PubMed and Embase was performed to assess AS progression over time in adult
      patients with AS measured by echocardiography. A total of 27 reports (15
      prospective, 12 retrospective, total 4,921 patients, pooled age 69 years) was
      included in which the baseline and progression rates of the hemodynamic variables
      were pooled. Subgroup analyses were performed to investigate factors associated
      with AS progression and sources of heterogeneity. RESULTS: Pooled annual AS
      progression was 3.70 mmHg per year (SE = 0.10) for randomized controlled trials,
      and 6.03 mmHg per year (SE = 0.10) for observational studies. A large variability
      in observed AS progression was found between studies, as well as a wide variety
      of methods employed to measure AS. CONCLUSION: The observed large individual
      variability in measuring AS progression among the selected studies calls for the
      implementation of a universal method of AS assessment. This will facilitate an
      insight into the determinants of AS progression and allow for an evidence-based
      tailoring of treatment.

PMID- 22953672
TI  - Rosuvastatin slows the development of diastolic dysfunction in calcific aortic
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aims were to test the effect of
      rosuvastatin on the progression of left ventricular (LV) diastolic function in
      patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic
      peptide (BNP) as a marker of diastolic dysfunction in this condition. METHODS:
      Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were
      administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60
      subjects with normal cholesterol levels remained untreated. The LV diastolic
      function was determined using conventional Doppler echocardiography, tissue
      Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the
      study and then assessed prospectively at six-month intervals until the study end.
      RESULTS: After an 18-month (mean 73 +/- 24 weeks) period of treatment with
      rosuvastatin (Tx group), patients showed a significantly better diastolic
      function than untreated subjects (uTx group), as indicated by an isovolumic
      relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx
      99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6
      versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p =
      0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4
      +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels
      of BNP were significantly lower in the Tx group than in the uTx group [median
      (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2
      pg/ml); p = 0.017]. CONCLUSION: The results of this prospective follow up study
      of asymptomatic patients showed that rosuvastatin treatment delays the
      progression of diastolic dysfunction in moderate AS when assessed using
      hemodynamic echocardiographic parameters or by the release of plasma
      physiological markers. Hence, the benefits of statin treatment in AS, which are
      known to affect the valve endothelium, also extend to changes affecting
      myocardial function itself.

PMID- 22953673
TI  - Aldosterone antagonists and chronic aortic regurgitation: promising but not quite
      ready for prime time.

PMID- 22953674
TI  - Potentially modifiable biological targets in aortic regurgitation.

PMID- 22953675
TI  - Effects of spironolactone treatment on an experimental model of chronic aortic
      valve regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic regurgitation (AR) is a disease for which
      there is currently no effective medical treatment. It has been shown previously
      in an experimental model of AR that the renin-angiotensin-aldosterone system
      (RAAS) plays a major role, and that medications blocking the RAAS are effective
      to protect against left ventricular (LV) hypertrophy and also help to maintain a
      normal systolic function. The role of aldosterone receptor blockers in this
      disease has never been evaluated. Thus, the effects were studied of the
      aldosterone receptor blocking agent spironolactone in a model of chronic AR in
      rats. METHODS: The effects of a six-month treatment with spironolactone were
      evaluated in adult Wistar rats with severe AR, compared to sham-operated and
      untreated AR animals. RESULTS: Spironolactone treatment decreased the total heart
      weight. In addition, the LV expression of atrial natriuretic peptide mRNA was
      decreased by spironolactone treatment, as was the expression of collagen 1 and
      LOX1 mRNAs. Left ventricular fibrosis was decreased by spironolactone treatment.
      CONCLUSION: Spironolactone protected against volume-overload cardiomyopathy in
      this model of aortic valve regurgitation. The predominant protective effect was a
      decrease in myocardial fibrosis.

PMID- 22953676
TI  - Urgent aortic valve replacement in octogenarians: does an 'urgent' status
      increase morbidity and mortality?
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the influence
      of 'urgent' status on short and long-term mortality and morbidity in a
      consecutive series of octogenarian patients who underwent aortic valve
      replacement (AVR). METHODS: Between January 2005 and March 2009, data were
      extracted for 141 consecutive patients aged over 80 years who underwent AVR
      either urgently (n = 49) or electively (n = 92). Early outcomes (in-hospital
      mortality, postoperative morbidities) and long-term outcomes were compared during
      a 39-month follow up period. The outcomes were compared after adjustment for
      differences in baseline risk factors. RESULTS: Patients of the 'urgent' group
      were older and had more comorbidities than those in the 'elective' group. There
      was a non-significant trend towards a higher in-hospital mortality in the
      'urgent' group (10.2% versus 4.3%, p = 0.18). The 39-month survival rate was 81%
      in elective patients, and 71% in urgent patients (p = 0.166). CONCLUSION: AVR can
      be performed in the elderly population with acceptable early and mid-term
      results, despite their urgent status. A large clinical trial is warranted to
      confirm the influence of an urgent status in octogenarian patients treated with
      surgical AVR.

PMID- 22953677
TI  - An automated coring and apical connector insertion device facilitates aortic
      valve bypass (apicoaortic conduit) surgery: preclinical experience in a chronic
      ovine model.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve bypass (AVB, apicoaortic conduit)
      surgery is an alternative treatment for high-risk patients with aortic stenosis
      (AS). An automated coring and connector insertion device designed to simplify the
      apical AVB anastomosis has been developed. The applicator consists of a toroidal
      shaft-mounted balloon, an integrated circular coring knife, and a stented apical
      connector supporting a Dacron graft. In this way, apical myocardial coring,
      connector insertion and core removal may be automated. METHODS: AVB was performed
      without cardiopulmonary bypass in eight sheep. A conduit containing a porcine
      valve was anastomosed to the descending aorta using a partial occlusion clamp.
      The applicator was used to insert the apical connector, and the connector and
      conduit were joined with a quick-connector. The descending aorta was occluded
      proximal to the distal anastomosis to simulate AS. Gradients across the conduit
      were measured after implantation, and one month later at sacrifice. RESULTS: All
      AVB implants were performed successfully. The median blood loss was 50 ml (IQR:
      13- 98 ml). The median connector implantation time was 29 s, and the peak
      gradients across the conduit early and at 30 days after AVB were 5.2 +/- 2.6 mmHg
      and 2.7 +/- 1.4 mmHg, respectively. One animal died of hemothorax at 24 h after
      surgery, but all remaining animals survived and gained weight. Gross and
      histopathologic assessments demonstrated widely patent conduits and normal brain
      histology in all animals. CONCLUSION: The applicator facilitated the safe and
      expeditious performance of AVB surgery. The clinical use of this device will
      improve the safety and increase the adoption of this beating-heart therapy for
      AS.

PMID- 22953678
TI  - Left atrial dissection after mitral valve replacement can mimic periprosthetic
      regurgitation.
AB  - Left atrial dissection is defined as a gap from the mitral or tricuspid annular
      area into the interatrial septum. It is most commonly occurs as a complication of
      mitral valve surgery. Herein, a patient is described who developed a left atrial
      dissection subsequent to multiple mitral valve procedures. The clinical
      presentation and surgical therapy for this condition is described with the aid of
      intraoperative photographic images. A brief discussion of this rare condition is
      also included, and the principles of surgical repair are elucidated.

PMID- 22953679
TI  - Aortopulmonary fistula after a modified Bentall procedure.
AB  - A 68-year-old man presented with aortic pseudoaneurysm and aortopulmonary
      fistula, due to dehiscence of the left coronary button anastomosis, at three
      months after surgery for acute aortic dissection using a composite conduit. At
      reoperation, the pulmonary trunk was repaired by direct suture and the coronary
      ostial anastomosis with single sutures, reinforced with pericardial pledgets from
      inside the aortic graft. Aortopulmonary fistula due to pseudoaneurysm formation
      is an extremely rare complication of operations on the proximal aorta.
      Furthermore, pseudoaneurysm caused by dehiscence of a coronary anastomosis
      complicated by an aortopulmonary fistula, as in the present case, has been
      previously reported only twice. Patients with acute aortic dissection, due to
      tissue fragility, appear particularly prone to develop such complications, which
      can occur even in the early postoperative period. Therefore, after the repair of
      acute aortic dissection, particularly when the insertion of a composite conduit
      is required, continuous follow up is mandatory for the early detection of this
      rare, but potentially lethal, complication.

PMID- 22953680
TI  - Lipid insudation as a cause of structural failure of a stentless pericardial
      bioprosthesis.
AB  - The Sorin Pericarbon Freedom (SPF) valve is a stentless bioprosthesis made from
      bovine pericardium, with a peculiar design aimed at preventing the mechanical
      failures observed with old models of stented pericardial bioprostheses. Herein,
      the case is described of a patient who presented with severe regurgitation of a
      SPF six years after aortic valve replacement, caused by commissural dehiscence.
      Both, microradiographic and histologic investigations, revealed mild calcific
      deposits and massive lipid infiltration, thus confirming that a patient-related
      mechanism such as 'atheromasia' can account for structural valve deterioration
      also in recipients of pericardial bioprostheses.

PMID- 22953681
TI  - A novel technique for quantifying mouse heart valve leaflet stiffness with atomic
      force microscopy.
AB  - BACKGROUND AND AIM OF THE STUDY: The use of genetically altered small animal
      models is a powerful strategy for elucidating the mechanisms of heart valve
      disease. However, while the ability to manipulate genes in rodent models is well
      established, there remains a significant obstacle in determining the functional
      mechanical properties of the genetically mutated leaflets. Hence, a feasibility
      study was conducted using micromechanical analysis via atomic force microscopy
      (AFM) to determine the stiffness of mouse heart valve leaflets in the context of
      age and disease states. METHODS: A novel AFM imaging technique for the
      quantification of heart valve leaflet stiffness was performed on cryosectioned
      tissues. Heart valve leaflet samples were obtained from wild-type mice (2 and 17
      months old) and genetically altered mice (10-month-old Notch1 heterozygous and 20
      month-old ApoE homozygous). Histology was performed on adjacent sections to
      determine the extracellular matrix characteristics of the scanned areas. RESULTS:
      The 17-month-old wild-type, 10-month-old Notch1, and 20-month-old ApoE aortic
      valve leaflets were all significantly stiffer than leaflets from 2-month-old wild
      type mice. Notch1 leaflets were significantly stiffer than all other leaflets
      examined, indicating that the Notch1 heterozygous mutation may alter leaflet
      stiffness, both earlier and to a greater degree than the homozygous ApoE
      mutation. However, these conclusions must be considered only preliminary due to
      the small sample size used in this proof-of-concept study. CONCLUSION: It is
      believed that this technique can provide a powerful end-point analysis for
      determining the mechanical properties of heart valve leaflets from genetically
      altered mice. Further, the technique is complementary to standard histological
      processing, and does not require excess tissue for mechanical testing. In this
      proof-of-concept study, AFM was shown to be a powerful tool for investigators of
      heart valve disease who develop genetically altered animals for their studies.

PMID- 22953682
TI  - Evolution of the Z-score in size-reduced bicuspid homografts.
AB  - BACKGROUND AND AIM OF THE STUDY: Human homografts are frequently used to
      establish an anatomic continuity between the right ventricular outflow tract
      (RVOT) and the pulmonary artery. Their limited availability, especially in small
      sizes, has encouraged the use of alternative strategies, such as size-reduced
      bicuspid homografts. The study aim was to analyze the follow up of patients who
      had received a standard tricuspid or size-reduced bicuspid homograft in the RVOT
      position, and to investigate modifications of the patients' Z-scores over the
      years. METHODS: A consecutive series of 107 patients aged < or = 16 years, who
      underwent RVOT repair between 1989 and 2010 to treat tetralogy of Fallot (ToF),
      was retrospectively reviewed. Of these patients, 17 received a size-reduced
      bicuspid pulmonary homograft, while 90 received a standard tricuspid homograft.
      The mean follow up periods were 10.5 years (range: 0.02-21.4 years) for the whole
      study population, and 11.8 years and 3.4 years, respectively, for the tricuspid
      and size-reduced bicuspid homograft groups. RESULTS: Freedom from mortality at 10
      years was 95 +/- 3%. During the observation period, 27 patients (31%) in the
      tricuspid homograft group and two (125) in the size-reduced bicuspid group
      presented with graft failure. According to the multivariable analysis, the only
      independent predictor of graft failure was patient age (hazards ratio 0.86). The
      17 patients who had received a size-reduced bicuspid homograft were then age
      matched to an equal-sized population of tricuspid homograft patients. A
      comparative analysis of the time-weighted average of the Z-scores for these
      tricuspid and size-reduced bicuspid homograft subgroups during the follow up
      period failed to identify any statistical difference (p = 0.5). CONCLUSION: In
      terms of Z-score evolution, size-reduced bicuspid homografts offer results which
      are comparable to those achieved with tricuspid homografts.

PMID- 22953683
TI  - Regional mechanical properties of human pulmonary root used for the Ross
      operation.
AB  - BACKGROUND AND AIM OF THE STUDY: Significant dilation of the pulmonary autograft
      after the Ross operation is problematic and requires reoperation. Autograft
      remodeling occurs in response to the immediate rise in pressure and consequent
      wall stress. The stress-strain response of the pulmonary root plays an important
      role in understanding the structural and functional changes of the autograft
      following the Ross procedure. At present, limited data are available on the
      mechanical properties of fresh human pulmonary roots; hence, the study aim was to
      determine the regional mechanical properties of human pulmonary roots. METHODS:
      Eighteen fresh healthy specimens of human pulmonary root were obtained from the
      California Transplant Donor Network (Oakland, CA, USA). Five regions of the
      pulmonary root--anterior and posterior pulmonary artery (PA), and each of the
      three sinuses--were subjected to displacement-controlled equibiaxial stretch
      testing within 24 h of cross-clamp time. Comparisons between the different
      regions of the pulmonary root were made based on tissue stiffness at physiologic
      stress. Histologic analyses were also performed of the fibrous structures of the
      PA and sinuses. RESULTS: Human PA and sinuses demonstrated a nonlinear response
      to loading, with no directional dependency to biaxial loading. The anterior PA
      was significantly more compliant than the posterior PA and the three sinuses in
      both circumferential and longitudinal directions (p < 0.04). However, there was
      no significant difference between the stiffness of the posterior PA and that of
      the three sinuses (p > 0.43), or among the three sinuses (p > 0.30) in the two
      directions. A tight, more dense weave of elastin was found in the anterior PA
      than in either the posterior PA or the sinuses. CONCLUSION: Significant inherent
      differences in compliance were demonstrated among different regions of the human
      pulmonary root. These regional differences may impact upon pulmonary autograft
      remodeling following the Ross operation, and also influence late autograft
      dilation.

PMID- 22953684
TI  - Bioactive porcine matrices in heart valve tissue engineering.
AB  - BACKGROUND AND AIM OF THE STUDY: Platelet gel (PG), a storage vehicle of growth
      factors, can be considered for the application of growth factors in combination
      with mesenchymal stem cells (MSCs) to accelerate tissue regeneration. Moreover,
      the addition of bioactive factors to porcine aortic valves could result in a more
      rapid repopulation. The study aim was to load acellular porcine aortic valve
      matrices with the PG-rich growth factors and to evaluate the effect on MSC
      repopulation. METHODS: Ovine mesenchymal stem cells (oMSCs) were isolated from
      sheep bone marrow. Acellular porcine heart valve matrices (n = 3) were preloaded
      with heparin and incubated with the PG for 2 h. A quantitative sandwich enzyme
      immunoassay was used to examine the release of basic fibroblast growth factor
      (bFGF) and transforming growth factor-beta (TGF-beta) from the matrices, oMSC
      repopulation was stimulated by static and dynamic culture. RESULTS: The
      immunoassays revealed that heparin-preloaded PG-incubated matrices showed a
      sustained release of 56.28 pg/ml bFGF and 30.66 ng/ml TGF-beta1 after 24 h.
      Dynamic culture induced oMSC invasion in growth factor-loaded matrices. Cell
      density results showed that dynamic culture significantly enhanced the
      repopulation of growth factor-loaded matrices (75 +/- 21 cells/mm2) when compared
      to static culture (26 +/- 10 cells/mm2). CONCLUSION: The incubation of a porcine
      aortic valve matrix with a PG concentrate creates a bioactive matrix. However,
      further fine-tuning of the PG concentration is necessary to take full advantage
      of platelet growth factor interaction between cells and the extracellular matrix
      in order to optimize cellular repopulation.

PMID- 22953685
TI  - Individualized quantified tricuspid valve annuloplasty for treating Ebstein
      anomaly.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate whether
      individualized quantified selective tricuspid valve annuloplasty would be
      suitable for the treatment of Ebstein anomaly. METHODS: Between March 1999 and
      February 2011, a total of 23 patients with Ebstein anomaly underwent
      individualized quantified selective tricuspid valve annuloplasty at the authors'
      institution. The annulus was reconstructed according to each patient's individual
      anatomic characteristics of their tricuspid valve. Echocardiography was used to
      assess the changes of tricuspid valve regurgitation and heart function
      perioperatively and also during the follow up period. RESULTS: There was no
      hospital mortality. One patient died suddenly at 41 months after surgery, and two
      patients were lost to follow up; the remaining patients are still alive. During
      the follow up, tricuspid valve regurgitation and cardiac function were improved
      in all patients postoperatively, with no acquired tricuspid stenosis. CONCLUSION:
      The study results and analysis of follow up data suggested that an
      '...individualized quantified selective concept and technique of tricuspid valve
      reconstruction' is reasonable, suitable, and practical in the treatment of
      Ebstein anomaly.

PMID- 22953686
TI  - Heart rupture and tamponade with a short review of cause of death in Ebstein
      anomaly.

PMID- 22953687
TI  - The psychology of time: a view backward and forward.
AB  - We selectively review the progress of research on the psychology of time during
      the past 125 years, starting with the publication of the first English-language
      psychological journal, The American Journal of Psychology. A number of important
      articles on the psychology of time appeared in this journal, including the widely
      cited early article by Nichols (1891). The psychology of time is a seminal topic
      of psychological science, and although it entered a phase of decline and even
      moribund neglect, the past several decades have seen a prominent renaissance of
      interest. This renewed vigor represents the rebirth of the recognition of the
      centrality of the psychology of time in human cognition and behavior. Our
      selective overview highlights a number of strands of progress and how they have
      helped lead to the present, in which the cognitive neuroscience of time and
      timing in the brain is one of the most fervent and fertile modern areas of brain
      research. We also discuss some remaining challenges and potential lines of
      progress.

PMID- 22953688
TI  - Collective action control by goals and plans: applying a self-regulation
      perspective to group performance.
AB  - In celebration of the 125th anniversary of The American Journal of Psychology,
      this article discusses a seminal publication by Marjorie Shaw (1932) on small
      group performance in the rational solution of complex problems. We then propose
      an approach for the effective regulation of group goal striving based on the
      collective action control perspective. From this perspective, group performance
      might be hindered by a collective intention-behavior gap: Groups fail to act on
      their intentions despite being strongly committed to the collective goal, knowing
      what the necessary actions are, and being capable of performing them. To reduce
      this gap, we suggest specific if-then plans (implementation intentions) in which
      groups specify when, where, and how to act toward their collective goal as an
      easily applicable self-regulation strategy to automate collective action control.
      Studies in which implementation intentions improved group performance in hidden
      profile, escalation of commitment, and cooperation task paradigms are reported
      and discussed.

PMID- 22953689
TI  - A century of imagery research: reflections on Cheves Perky's contribution to our
      understanding of mental imagery.
AB  - We review contemporary scientific research on the relationship between visual
      perception and visual mental imagery in the context of Cheves Perky's (1910)
      landmark article on imagery and imagination. This body of research has firmly
      established a strong connection between the psychology of imagery and perception
      and has contributed a strong voice to the imagery debate. We then use the concept
      of embodiment to discuss additional avenues of inquiry at which Perky's work
      hinted. These include a more thorough examination of the relationship between
      imagery and emotion, the creative, active aspects of imagery and imagination, and
      the methods we can bring to bear on understanding imagery and imagination as a
      human experience.

PMID- 22953690
TI  - Speech perception and reading: two parallel modes of understanding language and
      implications for acquiring literacy naturally.
AB  - I review 2 seminal research reports published in this journal during its second
      decade more than a century ago. Given psychology's subdisciplines, they would not
      normally be reviewed together because one involves reading and the other speech
      perception. The small amount of interaction between these domains might have
      limited research and theoretical progress. In fact, the 2 early research reports
      revealed common processes involved in these 2 forms of language processing. Their
      illustration of the role of Wundt's apperceptive process in reading and speech
      perception anticipated descriptions of contemporary theories of pattern
      recognition, such as the fuzzy logical model of perception. Based on the
      commonalities between reading and listening, one can question why they have been
      viewed so differently. It is commonly believed that learning to read requires
      formal instruction and schooling, whereas spoken language is acquired from birth
      onward through natural interactions with people who talk. Most researchers and
      educators believe that spoken language is acquired naturally from birth onward
      and even prenatally. Learning to read, on the other hand, is not possible until
      the child has acquired spoken language, reaches school age, and receives formal
      instruction. If an appropriate form of written text is made available early in a
      child's life, however, the current hypothesis is that reading will also be
      learned inductively and emerge naturally, with no significant negative
      consequences. If this proposal is true, it should soon be possible to create an
      interactive system, Technology Assisted Reading Acquisition, to allow children to
      acquire literacy naturally.

PMID- 22953691
TI  - Brightness of different hues is a single psychophysical ratio scale of intensity.
AB  - Recent studies based on testable behavioral axioms have concluded that
      psychological scales of subjective intensive attributes involving the ears and
      eyes form ratio scales. These studies have shown that a certain commutativity of
      proportion property must hold under either successive increases or successive
      decreases, with all other independent dimensions fixed. However, until recently
      limited attention has been paid to whether such subjective intensity scales
      differ when a dimension independent of intensity, such as frequency or wavelength
      (e.g., pitch in audition, hue in vision) is varied. Using a simple and favorably
      tested theoretical model for global psychophysics, Luce, Steingrimsson, and
      Narens (2010) arrived at a necessary and sufficient cross-frequency,
      commutativity condition for there to exist a common intensity ratio scale. Here
      we show that brightness--already established to be a ratio-scalable dimension-
      and hue satisfy the same conditions.

PMID- 22953692
TI  - Effect of prior practice on the stimulus-response compatibility effect in a mixed
      mapping environment.
AB  - A stimulus-response compatibility (SRC) effect is obtained when performance is
      better with compatible mappings than with incompatible mappings. When mappings
      are mixed within a task, the SRC effect is often eliminated or reversed.The
      present study examines how 1,600 trials with different practice tasks can affect
      the response selection process in these mixed mapping environments. Participants
      were assigned to one of three practice groups: mixed mapping, pure compatible
      mapping, and pure incompatible mapping. Subsequently, all participants performed
      an experimental session in which compatible and incompatible trials were
      mixed.The SRC effect was eliminated in the experimental mixed mapping session,
      regardless of practice condition. The results suggest that practice does not
      change the need to suppress the direct response selection route in a mixed
      mapping task. However, reaction time distributions and sequential analyses were
      modulated by practice condition, which indicates that the new associations
      acquired during practice may activate new routes that interact with preexisting
      ones.

PMID- 22953693
TI  - The illusion of fame: how the nonfamous become famous.
AB  - This article reports 2 experiments in which nonfamous faces were paired with
      famous (e.g., Oprah Winfrey) or semifamous (e.g., Annika Sorenstam) faces during
      an initial orienting task. In Experiment 1, the orienting task directed
      participants to consider the relationship between the paired faces. In Experiment
      2, participants considered distinctive qualities of the paired faces.
      Participants then judged the fame level of old and new nonfamous faces,
      semifamous faces, and famous faces. Pairing a nonfamous face with a famous face
      resulted in a higher fame rating than pairing a nonfamous face with a semifamous
      face. The fame attached to the famous people was misattributed to their nonfamous
      partners. We discuss this pattern of results in the context of current
      theoretical explanations of familiarity misattributions.

PMID- 22953694
TI  - Using heteromodal communication to optimize knowledge and awareness.
AB  - Accurate, error-free communication is essential for success in many areas, such
      as eyewitness testimony, human factors design, business, education, and personal
      relationships. Traditional communication uses similar modalities: Participants
      communicate by talking or by writing, but not both at the same time with the same
      addressees. New communicative technologies have broadened this vista. For
      example, one communicator can speak and the other can type. We tested
      communicative effectiveness using accuracy and error detection in a trivia recall
      test, evaluating the roles of presentation and retrieval modalities on reporting
      facts stored in long-term memory. Heteromodal communication (hearing and writing
      or reading and saying) was more effective than homomodal communication (hearing
      and saying or reading and writing), with the most correct responses and the most
      errors caught. This has direct connections to communicative success and applied
      tests of skill.

PMID- 22953695
TI  - Rotavirus A-specific single-domain antibodies produced in baculovirus-infected
      insect larvae are protective in vivo.
AB  - BACKGROUND: Single-domain antibodies (sdAbs), also known as nanobodies or VHHs,
      are characterized by high stability and solubility, thus maintaining the affinity
      and therapeutic value provided by conventional antibodies. Given these
      properties, VHHs offer a novel alternative to classical antibody approaches. To
      date, VHHs have been produced mainly in E. coli, yeast, plants and mammalian
      cells. To apply the single-domain antibodies as a preventive or therapeutic
      strategy to control rotavirus infections in developing countries (444,000 deaths
      in children under 5 years of age) has to be minimized their production costs.
      RESULTS: Here we describe the highly efficient expression of functional VHHs by
      the Improved Baculovirus Expression System (IBES(r) technology), which uses a
      baculovirus expression vector in combination with Trichoplusia ni larvae as
      living biofactories. Two VHHs, named 3B2 and 2KD1, specific for the inner capsid
      protein VP6 of Group A rotavirus, were expressed in insect larvae. The IBES(r)
      technology achieved very high expression of 3B2 and 2KD1, reaching 2.62% and
      3.63% of the total soluble protein obtained from larvae, respectively. These
      expression levels represent up to 257 mg/L of protein extract after insect
      processing (1 L extract represents about 125 g of insect biomass or about 375
      insect larvae). Larva-derived antibodies were fully functional when tested in
      vitro and in vivo, neutralizing Group A rotaviruses and protecting offspring mice
      against rotavirus-induced diarrhea. CONCLUSIONS: Our results open up the
      possibility of using insects as living biofactories (IBES(r) technology) for the
      cost-efficient production of these and other fully functional VHHs to be used for
      diagnostic or therapeutic purposes, thereby eliminating concerns regarding the
      use of bacterial or mammalian cells. To the best of our knowledge, this is the
      first time that insects have been used as living biofactories to produce a VHH
      molecule.

PMID- 22953696
TI  - Osmolyte-mediated encapsulation of proteins inside MS2 viral capsids.
AB  - The encapsulation of enzymes in nanometer-sized compartments has the potential to
      enhance and control enzymatic activity, both in vivo and in vitro. Despite this
      potential, there is little quantitative data on the effect of encapsulation in a
      well-defined compartment under varying conditions. To gain more insight into
      these effects, we have characterized two improved methods for the encapsulation
      of heterologous molecules inside bacteriophage MS2 viral capsids. First,
      attaching DNA oligomers to a molecule of interest and incubating it with MS2 coat
      protein dimers yielded reassembled capsids that packaged the tagged molecules.
      The addition of a protein-stabilizing osmolyte, trimethylamine-N-oxide,
      significantly increased the yields of reassembly. Second, we found that expressed
      proteins with genetically encoded negatively charged peptide tags could also
      induce capsid reassembly, resulting in high yields of reassembled capsids
      containing the protein. This second method was used to encapsulate alkaline
      phosphatase tagged with a 16 amino acid peptide. The purified encapsulated enzyme
      was found to have the same K(m) value and a slightly lower k(cat) value than the
      free enzyme, indicating that this method of encapsulation had a minimal effect on
      enzyme kinetics. This method provides a practical and potentially scalable way of
      studying the complex effects of encapsulating enzymes in protein-based
      compartments.

PMID- 22953697
TI  - Structural investigation of 1,1'-biphenyl-4-thiol self-assembled monolayers on
      Au(111) by scanning tunneling microscopy and low-energy electron diffraction.
AB  - Self-assembled monolayers (SAMs) of 1,1'-biphenyl-4-thiol (H-(C(6)H(4))(2)-SH) on
      Au(111) were prepared from solution or via vapor deposition in ultrahigh vacuum
      and characterized by scanning tunneling microscopy (STM), low-energy electron
      diffraction (LEED), and X-ray photoelectron spectroscopy (XPS). In contrast to
      the typically observed for densely packed alkane-thiol SAMs on Au(111) (?3 *
      ?3)R30 degrees  structure, the densely packed aromatic biphenylthiol SAMs
      prepared by both methods exhibit an unusual hexagonal (2 * 2) structure. Upon
      annealing at 100  degrees C, this structure evolves into the (2 * 7?3) structure
      resulting in the formation of highly ordered pinstripes oriented along the [1 -1
      0] directions. Lower density SAMs, prepared by vapor deposition in vacuum, show
      mixed structures comprising the hexagonal (2 * 2) structure and two rectangular
      arrangements with the unit cells of (3?3 * 9) and (2?3 * 8). An extinction of the
      (3?3 * 9) structure in the favor of the (2?3 * 8) structure is observed upon
      annealing at temperatures of ~100  degrees C.

PMID- 22953698
TI  - Proton exchange membrane developed from novel blends of polybenzimidazole and
      poly(vinyl-1,2,4-triazole).
AB  - In continuation (J. Phys. Chem. B2008, 112, 5305; J. Colloid Interface Sci. 2010,
      351, 374) of our quest for proton exchange membrane (PEM) developed from
      polybenzimidazole (PBI) blends, novel polymer blend membranes of PBI and poly(1
      vinyl-1,2,4-triazole) (PVT) were prepared using a solution blending method. The
      aim of the work was to investigate the effect of the blend composition on the
      properties, e.g., thermo-mechanical stability, swelling, and proton conductivity
      of the blend membranes. The presence of specific interactions between the two
      polymers in the blends were observed by studying the samples using varieties of
      spectroscopic techniques. Blends prepared in all possible compositions were
      studied using a differential scanning calorimetry (DSC) and exhibited a single
      T(g) value, which lies between the T(g) value of the neat polymers. The presence
      of a single composition-dependent T(g) value indicated that the blend is a
      miscible blend. The N-H...N interactions between the two polymers were found to
      be the driving force for the miscibility. Thermal stability up to 300  degrees C
      of the blend membranes, obtained from thermogravimetric analysis, ensured their
      suitability as PEMs for high-temperature fuel cells. The proton conductivity of
      the blend membranes have improved significantly, compared to neat PBI, because of
      the presence of triazole moiety, which acts as a proton facilitator in the
      conduction process. The blend membranes showed a considerably lower increase in
      thickness and swelling ratio than that of PBI after doping with phosphoric acid
      (PA). We found that the porous morphology of the blend membranes caused the
      loading of a larger amount of PA and, consequently, higher proton conduction with
      lower activation energy, compared to neat PBI.

PMID- 22953699
TI  - Morphology and behavior of the early stages of the skipper, Urbanus esmeraldus,
      on Urera baccifera, an ant-visited host plant.
AB  - The Neotropical genus Urbanus (Hubner) (Lepidoptera: Hesperiidae) contains around
      34 described species, and is widely distributed from the extreme southern United
      States to Argentina. Here, we describe the larval morphology and behavior of
      Urbanus esmeraldus (Hubner)(Hesperiidae) in Urera baccifera (Urticaceae), a plant
      producing food rewards and fleshy fruits that attract ants (including predacious
      species) in a Brazilian forest. Larvae pass through five instars and construct
      two kinds of leaf shelters. Experiments with ejected fecal pellets showed that
      these can serve as cues to ground-dwelling ants that climb onto host plants and
      potentially attack the larvae. Manipulation with pellets placed at different
      distances suggests that ejection behavior decreases larval vulnerability to ant
      predation. Larval preference for mature leaves may be related with increased
      predation risk at ant-visited young leaves. The study shows that a combination of
      natural history and experimental data can help understand the life history of a
      butterfly using a plant with high predation risk.

PMID- 22953700
TI  - Household chemicals, immune function, and allergy: a commentary.
AB  - In recent decades, in the US and in Western and Northern Europe, there has been a
      significant increase in the prevalence of atopic allergic disease. Although that
      increase may now be slowing, or have already reached a plateau, there remains
      considerable interest in the factor or factors that may have caused this
      increased susceptibility to allergy and asthma. Certainly, the changes recorded
      have been too rapid to implicate a change in the gene pool, and for that reason
      attention has focused on the possible impact of environmental, dietary, and
      lifestyle factors. Although the hygiene hypothesis proposes that increased
      susceptibility to allergic sensitization is associated with changes in childhood
      exposure pathogenic microorganisms, other factors have been considered also.
      Among these is exposure to chemicals and atmospheric pollutants. There is some
      evidence that exposure to certain chemicals may elicit or exacerbate respiratory
      reactions in those who are already sensitized, or who already have existing
      airway disease. However, a recent article has proposed that exposure to specific
      household cleaning products may be one factor that is able to affect
      susceptibility to allergic sensitization. In the light of that article it is
      timely now to consider again the ability of chemical exposure to influence
      sensitization to common antigens.

PMID- 22953702
TI  - Beyond nutrition: health-promoting foods by quorum-sensing inhibition.

PMID- 22953701
TI  - Single-photon emission computed tomography of spontaneous liver metastasis from
      orthotopically implanted human colon cancer cell line stably expressing human
      sodium/iodide symporter reporter gene.
AB  - BACKGROUND: We aimed to develop a mouse spontaneous liver metastasis model from
      an orthotopically implanted human colon cancer cell line stably expressing a
      human sodium/iodide symporter (NIS) reporter gene, which can be imaged with
      single-photon emission computed tomography (SPECT) using 99mTcO4-. METHODS: A
      recombinant plasmid containing a constitutively driven NIS gene (pcDNA3-NIS) was
      transfected into the human colon cancer cell line HCT116, and stable cell lines
      were established. The stable cells were subcutaneously injected into the nude
      mice. When the diameter reached 10 mm, the xenografts were excised, cut into
      small fragments, and orthotopically implanted into the cecal walls of another
      nude mice. 99mTcO4- SPECT/CT imaging was initiated 8 weeks later and repeated
      every 1 to 2 weeks. RESULTS: The production and function of NIS protein was
      confirmed in vitro by Western blotting and 99mTcO4- uptake assay. On SPECT/CT
      imaging, focal 99mTcO4- uptake was detected in the liver. Necropsy revealed local
      growth of the orthotopic colon xenografts with extensive invasion, microscopic
      serosal metastasis, and metastatic foci in the corresponding hepatic regions
      showing focal 99mTcO4- uptake. Immunohistochemistry revealed high levels of NIS
      expression in cells forming liver tumor, indicating that the liver tumor cells
      originated from the orthotopic colon xenografts. CONCLUSIONS: The present proof
      of-concept study provided a rationale for employing a radionuclide reporter gene
      for the specific visualization of spontaneous liver metastasis in living mice.
      This unique animal model of clinically relevant and externally detectable liver
      metastasis will be a powerful tool for investigating tumor biology and developing
      novel therapies for cancer metastasis.

PMID- 22953703
TI  - Fluconazole-resistant Candida: collateral damage associated with prior
      antibacterial exposure?

PMID- 22953705
TI  - The microbiome: the forgotten organ of the astronaut's body--probiotics beyond
      terrestrial limits.
AB  - Space medicine research has drawn immense attention toward provision of efficient
      life support systems during long-term missions into space. However, in extended
      missions, a wide range of diseases may affect astronauts. In space medicine
      research, the gastrointestinal microbiome and its role in maintaining astronauts'
      health has received little attention. We would like to draw researchers'
      attention to the significant role of microbiota. Because of the high number of
      microorganisms in the human body, man has been called a 'supra-organism' and
      gastrointestinal flora has been referred to as 'a virtual organ of the human
      body'. In space, the lifestyle, sterility of spaceship and environmental stresses
      can result in alterations in intestinal microbiota, which can lead to an impaired
      immunity and predispose astronauts to illness. This concern is heightened by
      increase in virulence of pathogens in microgravity. Thus, design of a personal
      probiotic kit is recommended to improve the health status of astronauts.

PMID- 22953706
TI  - Modes of action of Leishmanicidal antimicrobial peptides.
AB  - Leishmaniasis is one of the major neglected tropical diseases of the world. It is
      present in 88 countries with an estimated number of 500,000 cases of visceral
      leishmaniasis and 1.5 million cases of cutaneous disease. No effective
      vaccinations are available against leishmaniasis and the efficacy of existing
      treatments is compromised due to the emergence of drug resistance. Thus, there is
      an urgent need to develop new compounds with antileishmanial activity.
      Antimicrobial peptides have potential as novel antileishmanial therapy, either
      for use alone or in combination with current drug regimens. The modes of action
      of these peptides against Leishmania includes: membrane disruption leading to
      necrotic cell death; induction of apoptosis; binding to intracellular target(s);
      and indirect effects via immunomodulation of host immune cells. This article
      reviews the mechanisms of action of antimicrobial peptides with leishmanicidal
      activity.

PMID- 22953707
TI  - Biofilm-specific antibiotic resistance.
AB  - Bacterial biofilms are the basis of many persistent diseases. The persistence of
      these infections is primarily attributed to the increased antibiotic resistance
      exhibited by the cells within the biofilms. This resistance is multifactorial;
      there are multiple mechanisms of resistance that act together in order to provide
      an increased overall level of resistance to the biofilm. These mechanisms are
      based on the function of wild-type genes and are not the result of mutations.
      This article reviews the known mechanisms of resistance, including the ability of
      the biofilm matrix to prevent antibiotics from reaching the cells and the
      function of individual genes that are preferentially expressed in biofilms.
      Evidence suggests that these mechanisms have been developed as a general stress
      response of biofilms that enables the cells in the biofilm to respond to all of
      the changes in the environment that they may encounter.

PMID- 22953708
TI  - Moraxella catarrhalis: from interactions with the host immune system to vaccine
      development.
AB  - Moraxella catarrhalis is a human-restricted commensal that over the last two
      decades has developed into an emerging respiratory tract pathogen. The bacterial
      species is equipped with various adhesins to facilitate its colonization.
      Successful evasion of the human immune system is a prerequisite for Moraxella
      infection. This strategy involves induction of an excessive proinflammatory
      response, intervention of granulocyte recruitment to the infection site,
      activation of selected pattern recognition receptors and cellular adhesion
      molecules to counteract the host bacteriolytic attack, as well as, finally,
      reprogramming of antigen presenting cells. Host immunomodulator molecules are
      also exploited by Moraxella to aid in resistance against complement killing and
      host bactericidal molecules. Thus, breaking the basis of Moraxella immune evasion
      mechanisms is fundamental for future invention of effective therapy in
      controlling Moraxella infection.

PMID- 22953709
TI  - Tuberculous meningitis in adults: a review of a decade of developments focusing
      on prognostic factors for outcome.
AB  - Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment,
      mortality and long-term disability remain unacceptably high. Prevention, early
      recognition, diagnosis and treatment are fundamental to improving outcomes.
      However, an effective vaccine remains elusive, initial symptoms are nonspecific,
      and sensitive diagnostic tests are not available. There has been progress in our
      understanding of the immunopathology of TBM, and several factors have been found
      to be associated with susceptibility to infection, disease progression and
      clinical outcome. However, these have not yet impacted on treatment. Early
      treatment initiation and uninterrupted continuation, severity on presentation,
      seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and
      lactate levels, hyponatreamia and coinfection with HIV are all found to be
      important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and
      host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence
      susceptibility to TBM. However, these findings have not yet impacted on
      treatment. Progress in vaccine development, opportunities for better diagnostic
      tests, novel insights into pathogenesis and an increasing evidence base for
      improving treatment should impact the current high mortality and morbidity, if
      translated to global and local guidelines.

PMID- 22953710
TI  - SAMHD1: a novel antiviral factor in intrinsic immunity.
AB  - Some intracellular/membranous factors exert intrinsic immunity against viral
      pathogens. Most recently, SAMHD1 has been shown to be one of these factors.
      SAMHD1 is a nucleus-localized protein, and mutations in the gene are associated
      with Aicardi-Goutieres syndrome. As a triphosphohydrolase, it depletes the
      intracellular pool of dNTPs in myeloid cells, such as macrophages and dendritic
      cells, to a low level that establishes a precursor-deficient environment for the
      synthesis of lentiviral cDNA, thereby restricting viral replication in these host
      cells. However, some viruses evolve Vpx to recruit SAMHD1 onto the CRL4(DCAF1) E3
      ubiquitin ligase in the cytoplasm for proteasome-dependent degradation, by which
      these viruses relieve SAMHD1-mediated restriction of primate lentivirus
      infection. In this review, we describe the latest knowledge of SAMHD1 biology.

PMID- 22953713
TI  - Pertuzumab in HER2-positive breast cancer.
AB  - BACKGROUND: Lack of response in some patients and relapse during the course of
      therapy in the treatment of HER2-positive early breast cancer and metastatic
      breast cancer continue to challenge researchers and clinicians towards a better
      understanding of the fundamental mechanisms of trastuzumab action and new
      therapies for HER2. The aim of this review is to discuss current and future
      treatment options with pertuzumab in the light of new insights into HER2-positive
      breast cancer. SCOPE: Pertuzumab showed positive results in clinical studies and
      agents in routine clinical usage are updated. The PubMed database, ASCO and San
      Antonio Breast Cancer Symposium Meeting abstracts were searched up to June 2012
      by using the terms 'pertuzumab' and 'anti-HER2 treatment'; papers which were
      considered relevant for the aim of this review were selected by the authors.
      FINDINGS: The presented trials of phase II and phase III randomized trials of
      CLEOPATRA, NEOSPHERE and TRYPHAENA have showed pertuzumab action to be
      complementary to trastuzumab without increasing adverse events. Adding pertuzumab
      to trastuzumab in the first line of HER2-positive metastatic breast cancer and in
      the neoadjuvant treatment of locally advanced HER2-positive breast cancer is
      usually well tolerated. The evaluation of health-related quality of life showed
      that combining pertuzumab with docetaxel and trastuzumab compared to placebo have
      no detrimental effect with adding pertuzumab. CONCLUSION: Pertuzumab is the first
      HER dimerization inhibitor with a mechanism of action complementary to
      trastuzumab. Studies with anti-HER2 combination treatments indicate that the use
      of more than one HER2-targeted therapy was superior to one of these agents alone.
      Pertuzumab has produced impressive anti-tumor activity in combination with
      trastuzumab. There are ongoing studies with pertuzumab with an increasing
      tendency towards moving the study of these agents to earlier stages of the
      disease, namely in the adjuvant and neoadjuvant setting.

PMID- 22953714
TI  - "Brush-first" method for the parallel synthesis of photocleavable, nitroxide
      labeled poly(ethylene glycol) star polymers.
AB  - We describe the parallel, one-pot synthesis of core-photocleavable,
      poly(norbornene)-co-poly(ethylene glycol) (PEG) brush-arm star polymers (BASPs)
      via a route that combines the "graft-through" and "arm-first" methodologies for
      brush polymer and star polymer synthesis, respectively. In this method, ring
      opening metathesis polymerization of a norbornene-PEG macromonomer generates
      small living brush initiators. Transfer of various amounts of this brush
      initiator to vials containing a photocleavable bis-norbornene cross-linker
      yielded a series of water-soluble BASPs with low polydispersities and molecular
      weights that increased geometrically as a function of the amount of bis
      norbornene added. The BASP cores were cleaved upon exposure to UV light; the
      extent of photo-disassembly depended on the amount of cross-linker. EPR
      spectroscopy of nitroxide-labeled BASPs was used to probe differences between the
      BASP core and surface environments. We expect that BASPs will find applications
      as easy-to-synthesize, stimuli-responsive core-shell nanostructures.

PMID- 22953712
TI  - Greentree white paper: sexual violence, genitoanal injury, and HIV: priorities
      for research, policy, and practice.
AB  - The links between sexual violence, genitoanal injury, and HIV are understudied
      but potentially significant for understanding the epidemic's disproportionate
      impacts on young women and girls, particularly in sub-Saharan Africa, other
      hyperendemic areas, and conflict-affected regions. A Scientific Research Planning
      Meeting was convened by the Social Science Research Council at the Greentree
      Foundation in New York, March 19-20, 2012, bringing together an interdisciplinary
      group of researchers, clinicians, and policy makers to identify knowledge needs
      and gaps in three key areas: (1) the role of genitoanal injury on HIV
      transmission, acquisition, and pathogenesis; (2) the influence of sex and age
      related anatomic characteristics on HIV transmission, acquisition, and
      pathogenesis; and (3) the role of heterosexual anal intercourse in HIV
      transmission. This article reflects the consensus that emerged from the Greentree
      Meeting regarding priority scientific research questions in these three areas,
      associated data collection and measurement challenges and opportunities, and
      implications for policy and practice.

PMID- 22953715
TI  - An efficient synthesis of bridged heterocycles from an Ir(I) bis-amination/ring
      closing metathesis sequence.
AB  - The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the
      efficient formation of 2,6-divinyl heterocycles. Careful screening of amines,
      solvents, and conditions has led to the discovery of a system that favors
      formation of the desired cis products with synthetically useful levels of
      diastereoselectivity, and these results are further explained by computer based
      transition state energy calculations. Exposure of the heterocycles to ring
      closing metathesis catalysts leads to the desired bridged heterocyclic systems.

PMID- 22953716
TI  - Structural variations of single and tandem mismatches in RNA duplexes: a joint MD
      simulation and crystal structure database analysis.
AB  - Internal loops within RNA duplex regions are formed by single or tandem
      basepairing mismatches with flanking canonical Watson-Crick basepairs on both
      sides. They are the most common motif observed in RNA secondary structures and
      play integral functional and structural roles. In this report, we have studied
      the structural features of 1 * 1, 2 * 2, and 3 * 3 internal loops using all-atom
      molecular dynamics (MD) simulation technique with explicit solvent model. As MD
      simulation is intricately dependent on the choice of force-field and these are
      often rather approximate, we have used both the most popular force-fields for
      nucleic acids-CHARMM27 and AMBER94-for a comparative analysis. We find that
      tandem noncanonical basepairs forming 2 * 2 and 3 * 3 internal loops are
      considerably more stable than the single mismatches forming 1 * 1 internal loops,
      irrespective of the force field. We have also analyzed crystal structure database
      to study the conservation of these helical fragments in the corresponding sets of
      RNA structures. We observe that the nature of stability in MD simulations mimic
      their fluctuating natures in crystal data sets also, probably indicating reliable
      natures of both the force fields to reproduce experimental results. We also
      notice significant structural changes in the wobble G:U basepairs present in
      these double helical stretches, leading to a biphasic stability for these wobble
      pairs to release the deformational strains introduced by internal loops within
      duplex regions.

PMID- 22953718
TI  - Spinal canal surrogate for testing intradural implants.
AB  - We have designed, built and tested an anthropomorphic-scale surrogate spinal
      canal, for use in preliminary evaluations of the performance characteristics of a
      novel intradural spinal cord stimulator. The surrogate employs a silicone mock
      spinal cord with semi-major and semi-minor diameters of 10 and 6 mm,
      respectively, commensurate with those of actual thoracic-level spinal cord. The
      axial restoring force provided by the 300 um thick silicone denticulate ligament
      constructs on the mock cord is ~ 0.32 N mm(-1) over a 1.5 mm range of
      displacement, which is within a factor of 2 of that measured by others in human
      cadaver specimens. Examples of testing protocols of prototype intradural
      stimulators that employ this device are discussed.

PMID- 22953717
TI  - Profiling microRNAs in lung tissue from pigs infected with Actinobacillus
      pleuropneumoniae.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of non-protein-coding genes that play
      a crucial regulatory role in mammalian development and disease. Whereas a large
      number of miRNAs have been annotated at the structural level during the latest
      years, functional annotation is sparse. Actinobacillus pleuropneumoniae (APP)
      causes serious lung infections in pigs. Severe damage to the lungs, in many cases
      deadly, is caused by toxins released by the bacterium and to some degree by host
      mediated tissue damage. However, understanding of the role of microRNAs in the
      course of this infectious disease in porcine is still very limited. RESULTS: In
      this study, the RNA extracted from visually unaffected and necrotic tissue from
      pigs infected with Actinobacillus pleuropneumoniae was subjected to small RNA
      deep sequencing. We identified 169 conserved and 11 candidate novel microRNAs in
      the pig. Of these, 17 were significantly up-regulated in the necrotic sample and
      12 were down-regulated. The expression analysis of a number of candidates
      revealed microRNAs of potential importance in the innate immune response. MiR
      155, a known key player in inflammation, was found expressed in both samples.
      Moreover, miR-664-5p, miR-451 and miR-15a appear as very promising candidates for
      microRNAs involved in response to pathogen infection. CONCLUSIONS: This is the
      first study revealing significant differences in composition and expression
      profiles of miRNAs in lungs infected with a bacterial pathogen. Our results
      extend annotation of microRNA in pig and provide insight into the role of a
      number of microRNAs in regulation of bacteria induced immune and inflammatory
      response in porcine lung.

PMID- 22953719
TI  - Abnormality of cervical vestibular-evoked myogenic potentials and ocular
      vestibular-evoked myogenic potentials in patients with recurrent benign
      paroxysmal postitional vertigo.
AB  - CONCLUSION: Our results show that cervical vestibular-evoked myogenic potential
      (cVEMP) or ocular VEMP (oVEMP) abnormalities in the recurrent benign paroxysmal
      positional vertigo (BPPV) group were significantly higher than those in the non
      recurrent BPPV group. Therefore, we can infer that VEMP abnormality is one of
      risk factors for BPPV recurrence. OBJECTIVE: This prospective study aimed to test
      the hypothesis that otolith dysfunction using the VEMP test is a cause of
      recurrence of BPPV. METHODS: cVEMP and oVEMP tests using 500 Hz tone-burst
      stimuli were performed on 16 patients with recurrent BPPV between March 2010 and
      December 2011. Both VEMP tests were performed in 20 patients with non-recurrent
      BPPV. RESULTS: The differences in age, sex, and involved canal between the
      recurrent and non-recurrent BPPV groups were not significant. Abnormal cVEMP
      responses were detected in 5 of 16 (31.3%) subjects in the recurrent BPPV group
      and abnormal oVMEP responses were detected in 4 of 16 (25%) subjects in the
      recurrent BPPV group. When we defined VEMP abnormality as an abnormal cVEMP or
      abnormal oVEMP, VEMP abnormalities were detected in eight (50%) subjects in the
      recurrent BPPV group and in three (15%) subjects in the non-recurrent BPPV group;
      the difference between groups was significant.

PMID- 22953720
TI  - Enzyme-linked immunosorbent assay to diagnose human leptospirosis: a meta
      analysis of the published literature.
AB  - We report an evaluation of the accuracy of ELISA for the detection of Leptospira
      specific antibodies in humans. Eighty-eight studies published in 35 articles met
      all inclusion criteria and were submitted to meta-analysis. Pooled sensitivity
      and specificity were 0.779 (95% CI 0.770-0.789) and 0.913 (95% CI 0.908-0.917),
      respectively, and the area under the curve was 0.964. Heterogeneity across
      studies was statistically significant, but none of the sources of heterogeneity
      (disease stage, antigen used, antibody detected) could fully explain this
      finding. Although the convalescent stage of disease was significantly associated
      with higher diagnostic accuracy, IgM ELISA was the best choice, regardless of the
      stage of disease. Negative ELISAs (IgG or IgM) applied in the acute phase do not
      rule out leptospirosis due to the possibility of false-negative results. In this
      case it is advisable to request a second blood sample or to apply a direct method
      for leptospiral DNA.

PMID- 22953722
TI  - Direct patterning of silver particles on porous silicon by inkjet printing of a
      silver salt via in-situ reduction.
AB  - We have developed a method for obtaining a direct pattern of silver
      nanoparticles (NPs) on porous silicon (p-Si) by means of inkjet printing (IjP) of
      a silver salt. Silver NPs were obtained by p-Si mediated in-situ reduction of Ag+
      cations using solutions based on AgNO3 which were directly printed on p-Si
      according to specific geometries and process parameters. The main difference with
      respect to existing literature is that normally, inkjet printing is applied to
      silver (metal) NP suspensions, while in our experiment the NPs are formed after
      jetting the solution on the reactive substrate. We performed both optical and
      scanning electron microscopes on the NPs traces, correlating the morphology
      features with the IjP parameters, giving an insight on the synthesis kinetics.
      The patterned NPs show good performances as SERS substrates.

PMID- 22953723
TI  - When should we use nitrates in congestive heart failure?
AB  - Organic nitrates remain among the oldest and most commonly employed drugs in
      cardiology. Although, in most cases, their use in acute and chronic heart failure
      is based on clinical practice, only a few clinical trials have been conducted to
      evaluate their use in acute and chronic heart failure, most of which compare them
      with other drugs to evaluate differing endpoints. The purpose of this review is
      to examine the various trials that have evaluated the use of nitrates in acute
      and chronic heart failure.

PMID- 22953721
TI  - Pro-angiogenic and anti-inflammatory regulation by functional peptides loaded in
      polymeric implants for soft tissue regeneration.
AB  - Inflammation and angiogenesis are inevitable in vivo responses to biomaterial
      implants. Continuous progress has been made in biomaterial design to improve
      tissue interactions with an implant by either reducing inflammation or promoting
      angiogenesis. However, it has become increasingly clear that the physiological
      processes of inflammation and angiogenesis are interconnected through various
      molecular mechanisms. Hence, there is an unmet need for engineering functional
      tissues by simultaneous activation of pro-angiogenic and anti-inflammatory
      responses to biomaterial implants. In this work, the modulus and fibrinogen
      adsorption of porous scaffolds were tuned to meet the requirements (i.e., ~100
      kPa and ~10 nm, respectively), for soft tissue regeneration by employing tyrosine
      derived combinatorial polymers with polyethylene glycol crosslinkers. Two types
      of functional peptides (i.e., pro-angiogenic laminin-derived C16 and anti
      inflammatory thymosin beta4-derived Ac-SDKP) were loaded in porous scaffolds
      through collagen gel embedding so that peptides were released in a controlled
      fashion, mimicking degradation of the extracellular matrix. The results from (1)
      in vitro coculture of human umbilical vein endothelial cells and human blood
      derived macrophages and (2) in vivo subcutaneous implantation revealed the
      directly proportional relationship between angiogenic activities (i.e.,
      tubulogenesis and perfusion capacity) and inflammatory activities (i.e.,
      phagocytosis and F4/80 expression) upon treatment with either type of peptide.
      Interestingly, cotreatment with both types of peptides upregulated the angiogenic
      responses, while downregulating the inflammatory responses. Also, anti
      inflammatory Ac-SDKP peptides reduced production of pro-inflammatory cytokines
      (i.e., interleukin [IL]-1beta, IL-6, IL-8, and tumor necrosis factor alpha) even
      when treated in combination with pro-angiogenic C16 peptides. In addition to
      independent regulation of angiogenesis and inflammation, this study suggests a
      promising approach to improve soft tissue regeneration (e.g., blood vessel and
      heart muscle) when inflammatory diseases (e.g., ischemic tissue fibrosis and
      atherosclerosis) limit the regeneration process.

PMID- 22953724
TI  - Alternative splicing regulation and cell lineage differentiation.
AB  - The alternative splicing of precursor mRNA is an essential mechanism for protein
      diversity. It plays important biological roles, such as proliferation,
      differentiation and development of cells. Furthermore, alternative splicing
      participates in the pathogenesis of diseases, including cancer. Thus, in-depth
      understanding of splicing regulation is of great significance. Regulation of
      alternative splicing is an extraordinary complicated process in which several
      signal molecules are at work. Besides the cis-elements and trans-factors, several
      lines of evidences suggest that other molecules, structures or process also
      regulate splicing, such as RNA structures, transcription and transcription
      factors, chromatin and protein. Meanwhile, increasing body of evidence shows that
      alternative splicing correlated closely to stem cell lineage differentiation. It
      means that there is a fundamental role for splicing in controlling regulatory
      program required for cell lineage differentiation. This review systematically
      sums up the regulation of alternative splicing and summarizes the splicing events
      during cell lineage differentiation of stem cells.

PMID- 22953725
TI  - Free blastocyst and implantation stages in the European brown hare: correlation
      between ultrasound and histological data.
AB  - The European brown hare (Lepus europaeus) is the only species with
      superconception, whereby the maternal reproductive tract hosts two sets of
      conceptuses at different developmental stages. The embryonic development of the
      hare has not yet been described. To understand the mechanism of superconception,
      we studied oviduct transport and implantation stages by embryo flushing and live
      high-resolution ultrasound. Ultrasound data of implantation stages is correlated
      with histology. In the oviduct, a mucin coat is deposited on the zona pellucida.
      The blastocysts enter the uterine horns on Day 5, 1 day later than in the rabbit,
      and directly expand approximately threefold. Spacing is accompanied by
      peristaltic movement of the endometrium. The mucin coat disappears and the
      conceptuses attach. The yolk-sac expands in the blastocoel and syncytial knobs
      invade the antimesometrial endometrium. Maternal blood lacunae appear in the
      mesometrial endometrial folds, which are subsequently invaded by the
      syncytiotrophoblast. The haemochorial chorioallantoic placenta forms. The yolk
      sac cavity is gradually replaced by the allantois and finally by the exocoel. The
      different reproductive strategies of the precocial hare and the altricial rabbit
      are discussed. We assume that the lagomorph-specific mucin coat and the hare
      specific delay of the oviduct-uterine transition are prerequisites for
      superconception. 

PMID- 22953726
TI  - High insulin concentrations promote the in vitro growth and viability of canine
      preantral follicles.
AB  - To determine whether the effects of different concentrations of insulin on the
      development of canine preantral follicles in vitro were associated or not with
      FSH, secondary follicles were isolated and cultured. In Experiment 1, follicles
      were cultured in the following media: modified minimum essential medium (CtrlMEM)
      alone; CtrlMEM plus 5 ng mL-1 insulin (Ins5ng); CtrlMEM plus 10 ng mL-1 insulin
      (Ins10ng); and CtrlMEM plus 10 MUg mL-1 insulin. In Experiment 2, follicles were
      cultured in the same media but in the presence of sequential FSH (i.e. CtrlFSH,
      Ins5ngF, Ins10ngF and 10MUgF, respectively). Increasing concentrations of FSH
      (100, 500 and 1000 ng mL-1) were added sequentially to the culture medium on Days
      0, 6 and 12 of culture. Viability were assessed at the end of culture and
      follicular diameter and the antrum formation rate at four time points (Days 0, 6,
      12 and 18). In Experiment 1, the high insulin concentration significantly
      increased follicular viability (P<0.05). In contrast, in Experiment 2, viability
      was not affected by the inclusion of insulin. In addition, viability was
      significantly better in follicles cultured in CtrlFSH (P<0.05). The diameter of
      follicles in the high-insulin group in Experiment 1 and high-insulin plus FSH
      group in Experiment 2 was superior to other groups tested. In experiment 2, the
      Ins10MUg and Ins10MUgF groups exhibited significantly higher antrum formation
      rates than the other groups. In conclusion, in the absence of FSH, high
      concentrations of insulin have beneficial effects on follicular viability.
      However, to promote the growth of canine preantral follicles in vitro, it is
      recommended that a combination of insulin and FSH be added to the medium.

PMID- 22953727
TI  - Prevalence, risk factors and molecular epidemiology of methicillin-resistant
      Staphylococcus aureus (MRSA) colonization in residents of long-term care
      facilities in Luxembourg, 2010.
AB  - A prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) was
      performed in 2010 in 19 long-term care facilities in Luxembourg. Of the 954
      participating residents, 69 (7.2%) were colonized by MRSA. Previous history of
      MRSA [odds ratio (OR) 7.20, 95% confidence interval (CI) 3.19-16.27], quinolone
      therapy in the previous year (OR 2.27, 95% CI 1.17-4.41) and >=24 h care
      administered per week (OR 4.29, 95% CI 1.18-15.56) were independent risk factors
      for MRSA colonization. More than 75% of strains were of clonal complex (CC)5,
      mainly spa-type t003 or sequence type (ST)225 and ST710, which is a rapidly
      emerging lineage prevalent in central Europe. Five residents were colonized by
      livestock-associated genotypes belonging to CC398. Previously dominant CC8
      strains have recently been replaced by more resistant CC5 strains in Luxembourg.

PMID- 22953728
TI  - Increased prostaglandin E2-EP2 signalling in cumulus cells of female mice sired
      by males with the Y-chromosome long-arm deletion.
AB  - Cumuli oophori surrounding ovulated oocytes of B10.BR(Y(del)) females (sired by
      males with the Y-chromosome long-arm deletion) are more resistant to
      hyaluronidase digestion than cumuli oophori around eggs of genetically identical
      females but sired by males with the intact Y chromosome (B10.BR). This has been
      interpreted as a result of differences in paternal genome imprinting, which
      females of both groups inherit from their fathers. The following study shows that
      it is not hyaluronan, but rather excessive protein concentration, that makes the
      cumulus extracellular matrix of B10.BR(Y(del)) oocytes more resistant to
      enzymatic treatment. It was revealed, additionally, that cumulus cells around
      ovulating oocytes of B10.BR(Y(del)) females display higher surface accumulation
      of prostaglandin EP2 subtype receptors and higher expression of the Ptgs2 gene
      (encoding a rate-limiting enzyme of prostaglandin E2 synthesis) in relation to
      the cells of control B10.BR females. The expression levels of the prostaglandin
      dependent Tnfaip6 and Ccl2 genes were also altered in B10.BR(Y(del)) cumulus
      cells in a manner indicating increased prostaglandin signalling. The study
      provides further evidence for the divergence in reproductive phenotypes between
      B10.BR and B10.BR(Y(del)) female mice. It supports the hypothesis that genes of
      the Y-chromosome long arm may be involved in establishment of epigenetic marks in
      X-bearing spermatozoa.

PMID- 22953729
TI  - Prevalence and factors associated with overweight and obesity in French primary
      school children.
AB  - OBJECTIVE: To determine the prevalence of, and identify associated factors with,
      overweight and obesity in two samples of French children. DESIGN: We conducted
      two cross-sectional studies among two samples of children. Weight status, eating
      behaviour, sedentary activity, physical activity and parents' socio-economic
      status (SES) were collected using questionnaires filled by doctors during school
      health check-ups. Overweight and obesity were defined according to the age- and
      sex-specific BMI cut-off points of the International Obesity Taskforce.
      Multivariate analysis (logistic regression) was used to identify independent
      factors associated with overweight including obesity and obesity alone. SETTING:
      Aquitaine region (south-west France). SUBJECTS: Analyses were conducted among
      children aged 5-7 years (n 4048) and 7-11 years (n 3619). RESULTS: Overweight
      prevalence was 9.5 % including 2.2 % of obesity in 5-7-year-old children and 15.6
      % including 2.9 % of obesity in 7-11-year-old children. In both samples,
      overweight and obesity prevalence were higher in children whose parents had low
      or medium SES (P < 0.05). Factors associated significantly (P < 0.05) and
      independently with higher overweight or obesity prevalence were female gender,
      low or medium parental SES, never or sometimes having breakfast, never eating at
      the school canteen, never having a morning snack, never or sometimes having a
      light afternoon meal and having high sedentary activity. CONCLUSIONS: Our data
      confirm that low SES, absence of breakfast and high sedentary activity are
      associated with a higher risk of being overweight or obese, but also highlight
      original potential protective factors such as eating at the canteen and high meal
      frequency.

PMID- 22953730
TI  - Effectiveness Guidance Document (EGD) for acupuncture research - a consensus
      document for conducting trials.
AB  - BACKGROUND: There is a need for more Comparative Effectiveness Research (CER) to
      strengthen the evidence base for clinical and policy decision-making.
      Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The
      aim of this EGD is to provide specific recommendations for the design of
      prospective acupuncture studies to support optimal use of resources for
      generating evidence that will inform stakeholder decision-making. METHODS:
      Document development based on multiple systematic consensus procedures (written
      Delphi rounds, interactive consensus workshop, international expert review). To
      balance aspects of internal and external validity, multiple stakeholders
      including patients, clinicians and payers were involved. RESULTS: Recommendations
      focused mainly on randomized studies and were developed for the following areas:
      overall research strategy, treatment protocol, expertise and setting, outcomes,
      study design and statistical analyses, economic evaluation, and publication.
      CONCLUSION: The present EGD, based on an international consensus developed with
      multiple stakeholder involvement, provides the first systematic methodological
      guidance for future CER on acupuncture.

PMID- 22953731
TI  - CTen: a web-based platform for identifying enriched cell types from heterogeneous
      microarray data.
AB  - BACKGROUND: Interpreting in vivo sampled microarray data is often complicated by
      changes in the cell population demographics. To put gene expression into its
      proper biological context, it is necessary to distinguish differential gene
      transcription from artificial gene expression induced by changes in the cellular
      demographics. RESULTS: CTen (cell type enrichment) is a web-based analytical tool
      which uses our highly expressed, cell specific (HECS) gene database to identify
      enriched cell types in heterogeneous microarray data. The web interface is
      designed for differential expression and gene clustering studies, and the
      enrichment results are presented as heatmaps or downloadable text files.
      CONCLUSIONS: In this work, we use an independent, cell-specific gene expression
      data set to assess CTen's performance in accurately identifying the appropriate
      cell type and provide insight into the suggested level of enrichment to optimally
      minimize the number of false discoveries. We show that CTen, when applied to
      microarray data developed from infected lung tissue, can correctly identify the
      cell signatures of key lymphocytes in a highly heterogeneous environment and
      compare its performance to another popular bioinformatics tool. Furthermore, we
      discuss the strong implications cell type enrichment has in the design of
      effective microarray workflow strategies and show that, by combining CTen with
      gene expression clustering, we may be able to determine the relative changes in
      the number of key cell types.CTen is available at http://www.influenza
      x.org/~jshoemaker/cten/

PMID- 22953732
TI  - Ulopsina, a remarkable new ulopine leafhopper genus from China.
AB  - An unusual new cicadellid genus, Ulopsina gen. nov. and two new species, U.
      sinica sp. nov. and U. szwedoi sp. nov. from China are described, illustrated,
      and placed in the subfamily Ulopinae. The genus has characters of both the tribes
      Mesargini and Coloborrhinini, suggesting that the delimitation of these tribes
      may not be natural. The tribal placement of Ulopsina is uncertain. A checklist of
      the subfamily Ulopinae from China is also provided, and nine Chinese species
      designated under the genus Moonia are herein transferred to Mesargus, namely
      Mesargus albomaculata (Li) comb. nov., M. brevita (Cai et Shen) comb. nov., M.
      castanea (Kuoh) comb. nov., M. hei (Cai et Shen) comb. nov., M. hirsuta (Li)
      comb. nov., M. hyboma (Cai et Kuoh) comb. nov., M. maculigena (Kuoh) comb. nov.,
      M. serrata (Li and Zhang) comb. nov., and M. spinapenis (Li and Zhang) comb. nov.

PMID- 22953733
TI  - Structural variations of Si1-xCx and their light absorption controllability.
AB  - The emergence of third-generation photovoltaics based on Si relies on tunable
      bandgap materials with embedded nanocrystalline Si. One of the most promising
      approaches is based on the mixed-phase Si1 - xCx. We have investigated the light
      absorption controllability of nanocrystalline Si-embedded Si1 - xCx produced by
      thermal annealing of the Si-rich Si1 - xCx and composition-modulated superlattice
      structure. In addition, stoichiometric SiC was also investigated to comparatively
      analyze the characteristic differences. As a result, it was found that
      stoichiometric changes of the matrix material and incorporation of oxygen play
      key roles in light absorption controllability. Based on the results of this work
      and literature, a design strategy of nanocrystalline Si-embedded absorber
      materials for third-generation photovoltaics is discussed.

PMID- 22953734
TI  - Evaluation of primary and secondary responses to a T-cell-dependent antigen,
      keyhole limpet hemocyanin, in rats.
AB  - To develop a rat T-cell-dependent antibody response (TDAR) model evaluating both
      primary and secondary antibody responses, keyhole limpet hemocyanin (KLH) was
      used to immunize rats twice during a 14-day course of study, a pattern closely
      linked to that of a short-term general toxicity study. Female rats of four
      representative strains (e.g., Sprague-Dawley, Wistar, Fischer, and Lewis) were
      immunized twice with intravenous administrations of KLH (300 ug/rat) on Days 5
      and 9 during a 14-day treatment regimen with cyclophosphamide (CPA) at 1, 3, or 6
      mg/kg/day. The primary and secondary immunizations of KLH markedly elevated serum
      anti-KLH IgM and IgG levels in all strains on Days 9 and 15. Remarkable higher
      levels of anti-KLH IgG (~ 1000 ug/ml) were noted in all strains, which were more
      than 4-times compared with those of anti-KLH IgM levels at Day 9, indicating that
      predominant IgG reactions were induced by the dual immunizations. A large inter
      individual variability in KLH-specific IgM and IgG production was observed in all
      strains. However, levels of the KLH-specific antibodies were considered
      sufficient for the evaluation, even in Sprague-Dawley and Wistar rats reported as
      strains with a wide range of variability since immunosuppression of CPA on
      responses in both anti-KLH IgM and IgG were observed in all strains to the same
      extent. In addition, the sensitivity of the KLH-ELISA assay system detecting the
      immunosuppressive effects of CPA was comparable to other assay systems with PFC
      assay or ELISA using SRBC. The results here demonstrated that these experimental
      designs could provide valuable information about the influence on both the
      primary and secondary humoral immune responses in rats when exposed to potential
      immunomodulatory drugs. Furthermore, the design of the presented TDAR study would
      support comprehensive evaluation together with the outcome of the conventional
      general toxicity study.

PMID- 22953735
TI  - Specific numerical processing impairment in ALS patients.
AB  - The present study investigated for the first time numerical processing in
      sporadic amyotrophic lateral sclerosis (ALS) patients. Twenty-four non-demented
      patients affected by probable or definite ALS and 27 healthy controls underwent
      cognitive assessment. Numerical abilities (Number Comprehension, Number
      Transcoding, Arithmetic Fact retrieval, Calculation Skills and Arithmetic
      Principles) and neuropsychological functions were evaluated in accordance with
      Strong's consensus criteria. Clear group differences between the patients and
      controls were found in Multiplication Facts (Tables), Multiplication
      Approximation, and Multiplication Principles. These deficits were not
      statistically related to impairments of more general cognitive functioning. In
      conclusion, specific, previously unreported arithmetical deficits have been found
      in ALS patients. This particular impairment pattern could be indicative of damage
      to the cortico-subcortical circuits involved in some specific aspects of
      multiplication. Our findings could contribute to further delineate the profile of
      cognitive impairment in ALS.

PMID- 22953736
TI  - The initiation of non-invasive ventilation for patients with motor neuron
      disease: patient and carer perceptions of obstacles and outcomes.
AB  - This study aimed to examine the experiences of patients with motor neuron disease
      and their carers following the recommendation to use non-invasive ventilation
      (NIV). Qualitative interviews were carried out with 20 patients and 17 carers
      within one month of NIV being initiated. The study identified a range of
      potential barriers to usage including: adverse impressions of the technology;
      sleep disturbance; the sensation of pressure and pulsing; dry mouth; and mask
      design issues. Patients/carers perceived benefits related to: increased energy;
      improved sleeping; enhanced carer well-being; improved breathing and increased
      speech clarity. A key factor described by patients and carers was the need to
      persevere to overcome the challenges associated with early NIV use. The study
      highlights the importance of patient perceptions of gains as a factor in their
      NIV usage decisions. While recognizing that older individuals with limb-onset
      disease were over-represented in the sample, key recommendations from the study
      are: availability of easily accessible in-person support for patients; for
      clinicians to pre-empt potential obstacles by discussing options such as
      humidification or alternative mask interfaces; the importance of discussing
      potential benefits in detail with patients; and optimization of secretion
      management prior to NIV trial.

PMID- 22953737
TI  - Total duration of apnea and hypopnea events and average desaturation show
      significant variation in patients with a similar apnea-hypopnea index.
AB  - Obstructive sleep apnea (OSA) is commonly diagnosed based on the apnea-hypopnea
      index (AHI). Presently, novel indices were introduced for sleep apnea severity:
      total duration of sleep apnea and hypopnea events (TAHD%) and a combined index
      including duration and severity of the events (TAHD% * average desaturation). Two
      hundred and sixty-seven subjects were divided based on their AHI into four
      categories (normal, mild, moderate, severe OSA). In the most severe cases TAHD%
      exceeded 70% of the recorded time. This is important as excessive TAHD% may
      increase mortality and cerebro-vascular complications. Moreover, simultaneous
      increase in duration and frequency of apnea and hypopnea events leads to a
      paradoxical situation where AHI cannot increase along severity of the disease.
      Importantly, the combined index including duration and severity of the events
      showed significant variation between patients with similar apnea-hypopnea
      indices. To conclude, the present results suggest that the novel parameters could
      give supplementary information to AHI when diagnosing the severity of OSA.

PMID- 22953738
TI  - Epidemiology of Staphylococcus aureus in pigs and farmers in the largest farm in
      Dakar, Senegal.
AB  - Between December 2009 and November 2011, we collected 57 (12.3%) Staphylococcus
      aureus isolates from 464 pigs and 16 (30.8%) isolates from 52 farmers in the
      largest farm in Dakar. Fifty-one isolates (70%) belonged to four major multilocus
      sequence typing clonal complexes (CCs): CC152 (26.0%), CC15 (19.2%), CC5 (13.7%),
      and CC97 (10.9%). The CC variability among the pigs was similar to that observed
      among the farmers. Six isolates that were recovered only among pigs were
      resistant to methicillin (10.5%). They were assigned to the ST5-staphylococcal
      cassette chromosome mec type (SCCmec) IV (n = 5) and ST88-SCCmec IV (n = 1)
      clones. The luk-PV genes encoding Panton-Valentine leukocidin (PVL), present in
      43 (58.9%) isolates overall, including all major CCs and the MRSA ST5-SCCmec IV
      clone, were highly prevalent compared to data from industrialized countries. This
      finding is of major concern with regard to the potential virulence of these
      strains.

PMID- 22953739
TI  - Prevalence of Salmonella cerro in laboratory-based submissions of cattle and
      comparison with human infections in Pennsylvania, 2005-2010.
AB  - The aim of this study was to identify Salmonella serotypes infecting cattle in
      Pennsylvania, to compare infection rates for the predominant serotype, Salmonella
      enterica serotype Cerro, with the infection rates for the same serotype in
      humans, and to study the clonal diversity and antimicrobial resistance for this
      serotype in cattle from 2005 to 2010. Clonal diversity among the selected
      isolates was studied using pulsed-field gel electrophoresis (PFGE) and repetitive
      (rep)-polymerase chain reaction (PCR). Salmonella Cerro showed the single largest
      increase as a cause of cattle infections over the study period. The proportional
      distribution of Salmonella Cerro serotype among laboratory-submitted Salmonella
      positive cases in cattle was 36.1% in the year 2010 compared to 14.3% in 2005. A
      simultaneous decrease in serotype Newport infections was also observed in cattle
      (25% in 2005, to 10.1% in 2010). Studies of clonal diversity for cattle and human
      isolates revealed a predominant PFGE type but showed some variability. All tested
      isolates (n = 60) were susceptible to sulfamethoxazole-trimethoprim, but 2% of
      cattle isolates (n = 1/50) and 20% of human isolates (n = 2/10) showed resistance
      to tetracycline and sulfisoxazole. One human isolate showed additional resistance
      to ampicillin and gentamicin. This study suggests an increase in Salmonella Cerro
      infections in the cattle population and a decrease in Salmonella Newport
      infections. The increase in Cerro infections appears to be restricted to the
      cattle population, but occasional human infections occur.

PMID- 22953740
TI  - Antimicrobial resistance profiles of Enterococcus faecalis and Enterococcus
      faecium isolated from artisanal food of animal origin in Argentina.
AB  - Enterococci are part of the indigenous microbiota of human gastrointestinal tract
      and food of animal origin. Enterococci inhabiting non-human reservoirs play a
      critical role in the acquisition and dissemination of antimicrobial resistance
      determinants. The aim of this work was to investigate the antimicrobial
      resistance in Enterococcus faecalis and Enterococcus faecium strains recovered
      from artisanal food of animal origin. Samples of goat cheese (n = 42), cow cheese
      (n = 40), artisanal salami (n = 30), and minced meat for the manufacture of
      hamburgers (n = 60) were analyzed. Phenotypic and genotypic tests for species
      level identification of the recovered isolates were carried out. Minimum
      inhibitory concentration (MIC) study for in vitro quantitative antimicrobial
      resistance assessment was performed, and 71 E. faecalis and 22 E. faecium were
      isolated. The recovered enterococci showed different multi-drug resistance
      patterns that included tretracycline, erythromycin, ciprofloxacin, linezolid,
      penicillin, ampicillin, vancomycin, teicoplanin, gentamicin (high-level
      resistance), and streptomycin (high-level resistance). VanA-type E. faecium were
      detected. beta-lactamase activity was not observed. Artisanal foods of animal
      origin act as a non-human reservoir of E. faecalis and E. faecuim strains,
      expressing multi-resistance to antimicrobials. In conclusion, the implementation
      of a continuous antimicrobial resistance surveillance in enterococci isolated
      from artisanal food of animal origin is important.

PMID- 22953741
TI  - Antimicrobial resistance, virulence, and phylogenetic characteristics of
      Escherichia coli isolates from clinically healthy swine.
AB  - A total of 344 commensal Escherichia coli isolates from clinically healthy pigs
      were examined for antimicrobial resistance phenotypes, class 1 integrons,
      resistance genes, virulence gene profile, and phylogenetic groups. The majority
      of E. coli isolates were resistant to tetracycline (96.2%) and ampicillin
      (91.6%). Up to 98% were multidrug resistant. Seventy-three percent of the
      isolates carried class 1 integrons. Inserted-gene cassette arrays in variable
      regions included incomplete sat, aadA22, aadA1, dfrA12-aadA2, and sat-psp-aadA2,
      of which the aadA2 gene cassette was most prevalent (42.9%). Horizontal transfer
      was detected in eight E. coli isolates carrying class 1 integrons with dfrA12
      aadA2 gene cassette array. Sixteen resistance genes were identified among the E.
      coli isolates with corresponding resistance phenotype. Ten virulence genes
      (including elt, estA, estB, astA, faeG, fasA, fedA, eaeA, paa, and sepA) were
      detected, of which fasA was most commonly found (98.3%). Most of the E. coli
      isolates belonged to phylogenetic group B1. Significantly positive associations
      were observed between some virulence genes and some resistance phenotypes and
      genotypes (p < 0.05). The results support a finding that commensal E. coli have a
      role as reservoirs for antimicrobial resistance-encoding genes and virulence
      determinants.

PMID- 22953742
TI  - Effects of dietary alfalfa inclusion on Salmonella typhimurium populations in
      growing layer chicks.
AB  - Reducing Salmonella in poultry has been a paramount goal of the poultry industry
      in order to improve food safety. Inclusion of high-fiber fermentable feedstuffs
      in chicken diets has been shown to reduce the incidence of Salmonella
      colonization in laying hens, but no work has been performed in growing birds.
      Therefore, the present study was designed to quantify differences in artificially
      inoculated cecal Salmonella Typhimurium populations in growing layer chicks (n =
      60 in each of two replications) fed 0%, 25%, and 50% of their diet (w/w) replaced
      with alfalfa meal from day (d) 7 to d14 after hatch. Alfalfa supplementation
      reduced cecal populations of Salmonella by 0.95 and 1.25 log10 colony-forming
      unit per gram in the 25% and 50% alfalfa groups compared to controls. Alfalfa
      feeding reduced (p < 0.05) the number of cecal- and crop-positive birds compared
      to controls. Increasing levels of alfalfa increased (p < 0.05) total volatile
      fatty acids (VFA) and the proportion of acetate in the cecum. Surprisingly,
      alfalfa inclusion did not negatively impact average daily gain (ADG) in birds
      over the 7-d feeding period. Alfalfa inclusion at 50% of the diet increased (p <
      0.05) the number of bacterial genera detected in the cecum compared to controls,
      and also altered proportions of the microbial population by reducing Ruminococcus
      and increasing Clostridia populations. Results support the idea that providing a
      fermentable substrate can increase gastrointestinal VFA production and bacterial
      diversity which in turn can reduce colonization by Salmonella via natural
      competitive barriers. However, further studies are obviously needed to more fully
      understand the impact of changes made in diet or management procedures on poultry
      production.

PMID- 22953743
TI  - Development of bovine embryos derived from reproductive techniques.
AB  - Assisted reproduction techniques have improved agricultural breeding in the
      bovine. However, important development steps may differ from the situation in
      vivo and there is a high mortality rate during the first trimester of gestation.
      To better understand these events, we investigated the development of embryos and
      fetal membranes following fixed-time AI (FTAI), IVF and nuclear transfer (NT).
      The onset of yolk-sac development was not normal in cloned embryos. Later steps
      differed from conditions in vivo in all three groups; the yolk-sac was yellowish
      and juxtaposed with the amniotic membrane. Vascularisation of the chorioallantoic
      membrane was relatively late and low in NT gestations, but normal in the others.
      The overall development of the embryos was normal, as indicated by morphology and
      regression analysis of growth rate. However, NT conceptuses were significantly
      smaller, with the livers in some embryos occupying the abdominal cavity and
      others exhibiting heart abnormalities. In conclusion, the yolk-sac and the
      cardiovascular system seem to be vulnerable to morphogenetic alterations. Future
      studies will focus on gene expression and early vascularisation processes to
      investigate whether these changes may be responsible for the high incidence of
      intrauterine mortality, especially in clones. 

PMID- 22953744
TI  - Gender-specific abnormalities in the serotonin transporter system in panic
      disorder.
AB  - The central serotonergic system has been implicated in the pathophysiology of
      panic disorder (PD) by evidence of abnormally elevated serotonin-turnover,
      reduced pre- and post-synaptic 5-HT(1A)-receptor sensitivity and binding and
      clinical improvement during administration of agents that enhance serotonergic
      transmission. Polymorphisms in genes that putatively influence serotonergic
      neurotransmission increase the vulnerability for developing PD specifically in
      males. We tested the hypotheses that serotonin transporter (5-HTT) binding is
      elevated in PD subjects vs. healthy controls in regions where in vivo evidence
      exists for both elevated 5-HTT and 5-HT(1A) receptor levels in PD and
      investigated whether the extent of this difference depends upon gender.
      Volunteers were out-patients with current PD (n=24) and healthy controls (n=24).
      The non-displaceable component of 5-HTT binding-potential (BP(ND)) was measured
      using positron emission tomography and the 5-HTT selective radioligand,
      [(11)C]DASB. PD severity was assessed using the PD Severity Scale. The 5-HTT
      BP(ND) was increased in males with PD relative to male controls in the anterior
      cingulate cortex (F=8.96, p(FDR)=0.01) and midbrain (F=5.09, p(FDR)=0.03). In
      contrast, BP(ND) did not differ between females with PD and female controls in
      any region examined. The finding that 5-HTT-binding is elevated in males but not
      in females with PD converges with other evidence suggesting that dysfunction
      within the central serotonergic system exists in PD, and also indicates that such
      abnormalities are influenced by gender. These findings conceivably may reflect a
      sexual dimorphism that underlies the greater efficacy of serotonin reuptake
      inhibitor treatment in females vs. males with PD.

PMID- 22953745
TI  - The application of hyaluronic acid hydrogels to retinal progenitor cell
      transplantation.
AB  - Control of retinal progenitor cell (RPC) survival, delivery, and differentiation
      following transplantation into the retina remains a challenge. This is largely
      due to the use of culture systems that involve poorly defined animal products and
      do not mimic the natural developmental milieu. We describe the use of hyaluronic
      acid (HA) based hydrogels to encapsulate mouse RPCs and a delivery system for
      injectable tissue engineering. We selected HA because of its role in early
      development and as a feeder layer in stem cell cultures, and the relative ease
      with which various parameters can be controlled (e.g., hydrogel architecture,
      mechanics, and degradation). When encapsulated in three-dimensional HA hydrogels,
      RPCs maintained their undifferentiated state and readily formed neurospheres.
      These hydrogels were viscous solutions, exhibiting properties ideal for delivery
      to a subretinal space. The transplants caused very little disruption to the host
      retinal architecture. Hydrogels were completely degraded and RPCs distributed
      evenly in the subretinal space by week 3 and expressed the mature photoreceptor
      marker recoverin. HA hydrogels, with their developmentally relevant composition
      and malleable physical properties, provide a unique microenvironment for self
      renewal and differentiation of RPCs for retinal repair.

PMID- 22953746
TI  - Nanocarbon-based photovoltaics.
AB  - Carbon materials are excellent candidates for photovoltaic solar cells: they are
      Earth-abundant, possess high optical absorption, and maintain superior thermal
      and photostability. Here we report on solar cells with active layers made solely
      of carbon nanomaterials that present the same advantages of conjugated polymer
      based solar cells, namely, solution processable, potentially flexible, and
      chemically tunable, but with increased photostability and the possibility to
      revert photodegradation. The device active layer composition is optimized using
      ab initio density functional theory calculations to predict type-II band
      alignment and Schottky barrier formation. The best device fabricated is composed
      of PC(70)BM fullerene, semiconducting single-walled carbon nanotubes, and reduced
      graphene oxide. This active-layer composition achieves a power conversion
      efficiency of 1.3%-a record for solar cells based on carbon as the active
      material-and we calculate efficiency limits of up to 13% for the devices
      fabricated in this work, comparable to those predicted for polymer solar cells
      employing PCBM as the acceptor. There is great promise for improving carbon-based
      solar cells considering the novelty of this type of device, the high
      photostability, and the availability of a large number of carbon materials with
      yet untapped potential for photovoltaics. Our results indicate a new strategy for
      efficient carbon-based, solution-processable, thin film, photostable solar cells.

PMID- 22953747
TI  - Pharmacokinetics and blood-brain barrier penetration of (+)-catechin and (-)
      epicatechin in rats by microdialysis sampling coupled to high-performance liquid
      chromatography with chemiluminescence detection.
AB  - (+)-Catechin (C) and (-)-epicatechin (EC), as the basic monomer units of
      flavanols, can be widely found in natural products or medicinal herbs. Recent
      pharmacological studies have revealed that C and EC exhibit good neuroprotective
      effects. However, there is little information about pharmacokinetic profiles in
      the brain and in vivo BBB penetration of C and EC. In this paper, an
      ultrasensitive method using high-performance liquid chromatography (HPLC) with
      chemiluminescence (CL) detection was developed for the analysis of microdialysis
      samples. The detection limits for C and EC in Ringer's solution were 1.0 and 1.2
      ng/mL, respectively. The intraday and interday accuracies for C and EC in
      Ringer's solution ranged from -3.0 to 4.4%, and the intraday and interday
      precisions were below 5.2%. The mean in vivo recoveries of C and EC in
      microdialysis probes were 33.7% and 26.5% in blood while 38.3% and 29.1% in
      brain. Pharmacokinetic parameters were estimated using the statistical moment
      method after iv administration (C and EC, 20 mg/kg of body weight) in rats. Brain
      to-blood (AUC(brain)/AUC(blood)) distribution ratios were 0.0726 +/- 0.0376 for C
      and 0.1065 +/- 0.0531 for EC, indicating that C and EC could pass through the
      BBB, which is further evidence of their neuroprotective effects.

PMID- 22953749
TI  - Functionalized chromans and isochromans via a diastereoselective Pd(0)-catalyzed
      carboiodination.
AB  - A diastereoselective approach to isochromans and chromans via Pd(0)-catalyzed
      carboiodination is reported. The transformations using this methodology display
      excellent yields and diastereoselectivities as well as broad functional group
      compatibility. The selectivity observed in these cyclizations, forming isochroman
      or chroman targets, is postulated to originate from the minimization of A(1,2)
      strain and axial-axial interactions, respectively. This method has also been used
      to highlight the concept of reversible oxidative addition to carbon-iodine bonds
      in polyiodinated substrates.

PMID- 22953748
TI  - Mothers' experiences in the Nurse-Family Partnership program: a qualitative case
      study.
AB  - BACKGROUND: Few studies have explored the experiences of low income mothers
      participating in nurse home visiting programs. Our study explores and describes
      mothers' experiences participating in the Nurse-Family Partnership (NFP) Program,
      an intensive home visiting program with demonstrated effectiveness, from the time
      of program entry before 29 weeks gestation until their infant's first birthday.
      METHODS: A qualitative case study approach was implemented. A purposeful sample
      of 18 low income, young first time mothers participating in a pilot study of the
      NFP program in Hamilton, Ontario, Canada partook in one to two face to face in
      depth interviews exploring their experiences in the program. All interviews were
      digitally recorded and transcribed verbatim. Conventional content analysis
      procedures were used to analyze all interviews. Data collection and initial
      analysis were implemented concurrently. RESULTS: The mothers participating in the
      NFP program were very positive about their experiences in the program. Three
      overarching themes emerged from the data: 1. Getting into the NFP program; 2. The
      NFP nurse is an expert, but also like a friend providing support; and 3.
      Participating in the NFP program is making me a better parent. CONCLUSIONS: Our
      findings provide vital information to home visiting nurses and to planners of
      home visiting programs about mothers' perspectives on what is important to them
      in their relationships with their nurses, how nurses and women are able to
      develop positive therapeutic relationships, and how nurses respond to mothers'
      unique life situations while home visiting within the NFP Program. In addition
      our findings offer insights into why and under what circumstances low income
      mothers will engage in nurse home visiting and how they expect to benefit from
      their participation.

PMID- 22953750
TI  - Temporal trends of asthma mortality rates in Brazil from 1980 to 2010.
AB  - OBJECTIVE: Mortality from asthma has varied among countries during the last
      several decades. This study aimed to identify temporal trends of asthma mortality
      in Brazil from 1980 to 2010. METHOD: We analyzed 6840 deaths of patients aged 5
      34 years that occurred in Brazil with the underlying cause of asthma. We applied
      a log-linear model using Poisson regression to verify peaks and trends. We also
      calculated the point estimation and 95% confidence interval (CI 95%) of the
      annual percent change (APC) of the mortality rates, and the average annual
      percent change (AAPC) for 2001-2010. RESULTS: A decline was observed from 1980 to
      1992 [APC = -3.4 (-5.0 to -1.8)], followed by a nonsignificant rise until 1996
      [APC = 6.8 (-1.4 to 15.6)], and a new downward trend from 1997 to 2010 [APC = 
      2.7 (-3.9 to -1.6)]. The APCs varied according to age strata: 5-14 years from
      1980 to 2010 [-0.3 (-1.1 to 0.5)]; 15-24 years from 1980 to 1991 [-2.1 (-5.0 to
      0.9)], from 1992 to 1996 [6.8 (-6.7 to 22.2)], and from 1997 to 2010 [-3.9 (-5.7
      to -2.0)]; 24-25 years from 1980 to 1992 [-2.5 (-4.6 to -0.3)], from 1993 to 1995
      [12.0 (-21.1 to 59.1)], and from 1996-2010 [-1.7 (-3.0 to -0.4)]. AAPC from 2001
      to 2010 was -1.7 (-3.0 to -0.4); the decline for this period was significant for
      patients over 15 years old, women, and those living in the Southeast region.
      CONCLUSION: Asthma mortality rates in Brazil have been declining since the late
      1990s.

PMID- 22953751
TI  - Functionalized carbon nanotubes mixed matrix membranes of polymers of intrinsic
      microporosity for gas separation.
AB  - The present work reports on the gas transport behavior of mixed matrix membranes
      (MMM) which were prepared from multi-walled carbon nanotubes (MWCNTs) and
      dispersed within polymers of intrinsic microporosity (PIM-1) matrix. The MWCNTs
      were chemically functionalized with poly(ethylene glycol) (PEG) for a better
      dispersion in the polymer matrix. MMM-incorporating functionalized MWCNTs (f
      MWCNTs) were fabricated by dip-coating method using microporous polyacrylonitrile
      membrane as a support and were characterized for gas separation performance. Gas
      permeation measurements show that MMM incorporated with pristine or
      functionalized MWCNTs exhibited improved gas separation performance compared to
      pure PIM-1. The f-MWCNTs MMM show better performance in terms of permeance and
      selectivity in comparison to pristine MWCNTs. The gas permeances of the derived
      MMM are increased to approximately 50% without sacrificing the selectivity at 2
      wt.% of f-MWCNTs' loading. The PEG groups on the MWCNTs have strong interaction
      with CO2 which increases the solubility of polar gas and limit the solubility of
      nonpolar gas, which is advantageous for CO2/N2 selectivity. The addition of f
      MWCNTs inside the polymer matrix also improved the long-term gas transport
      stability of MMM in comparison with PIM-1. The high permeance, selectivity, and
      long term stability of the fabricated MMM suggest that the reported approach can
      be utilized in practical gas separation technology.

PMID- 22953752
TI  - Prevalence of foodborne pathogens in retailed foods in Thailand.
AB  - The consumption of foodborne pathogens contaminated in food is one of the major
      causes of diarrheal diseases in Thailand. The objective of this study was to
      evaluate the prevalence and types of contaminating bacteria in retailed
      foodstuffs in Thailand. Food from four categories (137 samples total), including
      meat (51 samples), vegetables (38 samples), fish or seafood (37 samples), and
      fermented food (11 samples), was purchased randomly from seven different open
      markets and seven supermarkets in Thailand from August 2010 to March 2011. Seven
      types of major foodborne pathogens were identified using conventional culture
      methods. Approximately 80% of meat samples tested was contaminated with
      Salmonella spp. In contrast, the Salmonella spp. contamination rate of vegetable
      (5%) or fermented food (9%) samples was comparatively low. Six strains of
      Cronobacter sakazakii and two strains of Yersinia enterocolitica were also
      isolated. A substantially higher rate of contamination by Bacillus cereus was
      observed in fermented food (82%) than in samples of meat (2%) and fish or seafood
      (5%). Seven Listeria spp. isolates were obtained from meat and fish or seafood
      samples. Approximately 39% of samples tested were found to be contaminated with
      Staphylococcus spp. (54 isolates). The rate of bacterial contamination of meat
      did not depend on the type of market. However, the contamination rate of
      Staphylococcus spp. in vegetables was higher in open markets than in
      supermarkets, and the contamination rate of Salmonella spp. and Staphylococcus
      spp. in fish or seafood samples purchased in open markets was likewise higher
      than in those purchased in supermarkets. Therefore, improvement of hygienic
      practices throughout the food chain may be required to reduce the risk of food
      poisoning.

PMID- 22953753
TI  - Iron particle size effects for direct production of lower olefins from synthesis
      gas.
AB  - The Fischer-Tropsch synthesis of lower olefins (FTO) is an alternative process
      for the production of key chemical building blocks from non-petroleum-based
      sources such as natural gas, coal, or biomass. The influence of the iron carbide
      particle size of promoted and unpromoted carbon nanofiber supported catalysts on
      the conversion of synthesis gas has been investigated at 340-350  degrees C,
      H(2)/CO = 1, and pressures of 1 and 20 bar. The surface-specific activity
      (apparent TOF) based on the initial activity of unpromoted catalysts at 1 bar
      increased 6-8-fold when the average iron carbide size decreased from 7 to 2 nm,
      while methane and lower olefins selectivity were not affected. The same decrease
      in particle size for catalysts promoted by Na plus S resulted at 20 bar in a 2
      fold increase of the apparent TOF based on initial activity which was mainly
      caused by a higher yield of methane for the smallest particles. Presumably,
      methane formation takes place at highly active low coordination sites residing at
      corners and edges, which are more abundant on small iron carbide particles. Lower
      olefins are produced at promoted (stepped) terrace sites that are available and
      active, quite independent of size. These results demonstrate that the iron
      carbide particle size plays a crucial role in the design of active and selective
      FTO catalysts.

PMID- 22953755
TI  - Hypo- and hyperglycemia in relation to the mean, standard deviation, coefficient
      of variation, and nature of the glucose distribution.
AB  - AIMS: We describe a new approach to estimate the risks of hypo- and hyperglycemia
      based on the mean and SD of the glucose distribution using optional
      transformations of the glucose scale to achieve a more nearly symmetrical and
      Gaussian distribution, if necessary. We examine the correlation of risks of hypo-
      and hyperglycemia calculated using different glucose thresholds and the
      relationships of these risks to the mean glucose, SD, and percentage coefficient
      of variation (%CV). MATERIALS AND METHODS: Using representative continuous
      glucose monitoring datasets, one can predict the risk of glucose values above or
      below any arbitrary threshold if the glucose distribution is Gaussian or can be
      transformed to be Gaussian. Symmetry and gaussianness can be tested objectively
      and used to optimize the transformation. RESULTS: The method performs well with
      excellent correlation of predicted and observed risks of hypo- or hyperglycemia
      for individual subjects by time of day or for a specified range of dates. One can
      compare observed and calculated risks of hypo- and hyperglycemia for a series of
      thresholds considering their uncertainties. Thresholds such as 80 mg/dL can be
      used as surrogates for thresholds such as 50 mg/dL. We observe a high correlation
      of risk of hypoglycemia with %CV and illustrate the theoretical basis for that
      relationship. CONCLUSIONS: One can estimate the historical risks of hypo- and
      hyperglycemia by time of day, date, day of the week, or range of dates, using any
      specified thresholds. Risks of hypoglycemia with one threshold (e.g., 80 mg/dL)
      can be used as an effective surrogate marker for hypoglycemia at other thresholds
      (e.g., 50 mg/dL). These estimates of risk can be useful in research studies and
      in the clinical care of patients with diabetes.

PMID- 22953754
TI  - A randomized comparison of online- and telephone-based care management with
      internet training alone in adult patients with poorly controlled type 2 diabetes.
AB  - AIMS: Care management may improve the quality of diabetes care by enhancing
      contact between high-risk patients and their providers. This prospective,
      longitudinal, randomized trial sought to investigate whether telephone or online
      care management improves diabetes-related outcomes over time compared with usual
      care supplemented with Internet access and training. SUBJECTS AND METHODS: One
      hundred fifty-one adult subjects with type 2 diabetes mellitus and an elevated
      hemoglobin A1c (A1c) level (>=8.5%) were randomly assigned to online care
      management (n=51), telephone-based care management (n=51), or Web training (n=49)
      groups. Online and telephone participants interacted with a care manager through
      a diabetes education and care management Web site and by telephone, respectively.
      The Web training group was provided with online diabetes self-management
      resources but no care management support. The primary outcome measure was A1c
      measured every 3 months for a year. RESULTS: A1c declined significantly and
      substantially in all groups over 12 months. A1c declined linearly at a rate of
      0.32% (P<0.0001) per quarter for the online group, 0.36% (P<0.0001) for the
      telephone group, and 0.41% for the Web training group (P<0.0001). The rate of
      change over time did not differ significantly among groups. The groups converged
      at 12 months with average absolute A1c difference of -1.5%. The number of
      interactions with care providers was not significantly associated with the change
      in A1c. Blood pressure, weight, lipid levels, and diabetes distress did not
      differ among groups over time. CONCLUSIONS: Online, telephone-based care
      management, and Web training for diabetes patients with elevated A1c were each
      associated with a substantial improvement in A1c over a 1-year period. Internet
      access and training alone may be as effective as care management in patients with
      poorly controlled diabetes.

PMID- 22953756
TI  - Cryotolerance of in vitro-produced porcine blastocysts is improved when using
      glucose instead of pyruvate and lactate during the first 2 days of embryo
      culture.
AB  - The objective of the present study was to determine the effects of replacing
      glucose with pyruvate and lactate during the first 48 h of in vitro culture (IVC)
      in NCSU-23 medium on embryo development, embryo quality and survival of porcine
      blastocysts after vitrification. To this end, in vitro-produced (IVP) porcine
      oocytes were cultured with either glucose for 6 days (IVC-Glu) or pyruvate
      lactate from Day 0 to Day 2 and then with glucose until Day 6 (IVC-PyrLac).
      Blastocysts were vitrified on Day 6 using the Cryotop device and, after warming,
      survival rate and the apoptosis index were evaluated after 24 h incubation in
      NCSU-23 medium. No significant differences were observed between IVC-Glu and IVC
      PyrLac in terms of cleavage rate, blastocyst yield, total number of cells per
      blastocyst or the apoptosis index (1.82+/-0.75% vs 3.18+/-0.88%, respectively) of
      non-vitrified embryos. However, a significant increase was seen in
      hatching/hatched blastocysts in the IVC-PyrLac compared with IVC-Glu treatment
      group (12.71+/-1.20% vs 3.54+/-0.47%, respectively). Regardless of treatment,
      vitrification impaired the survival rate and the apoptosis index. When comparing
      both treatments after warming, the percentage of apoptotic cells was
      significantly higher for blastocysts in the IVC-PyrLac compared with IVC-Glu
      group (18.55+/-3.49% vs 9.12+/-2.17%, respectively). In conclusion, under the
      conditions of the present study, replacement of glucose with pyruvate-lactate
      during the first 48 h of culture resulted in a lower cryotolerance of IVP porcine
      embryos.

PMID- 22953757
TI  - High-resolution structural insights into bone: a solid-state NMR relaxation study
      utilizing paramagnetic doping.
AB  - The hierarchical heterogeneous architecture of bone imposes significant
      challenges to structural and dynamic studies conducted by traditional biophysical
      techniques. High-resolution solid-state nuclear magnetic resonance (SSNMR)
      spectroscopy is capable of providing detailed atomic-level structural insights
      into such traditionally challenging materials. However, the relatively long data
      collection time necessary to achieve a reliable signal-to-noise ratio (S/N)
      remains a major limitation for the widespread application of SSNMR on bone and
      related biomaterials. In this study, we attempt to overcome this limitation by
      employing the paramagnetic relaxation properties of copper(II) ions to shorten
      the (1)H intrinsic spin-lattice (T(1)) relaxation times measured in natural
      abundance (13)C cross-polarization (CP) magic-angle-spinning (MAS) NMR
      experiments on bone tissues for the purpose of accelerating the data acquisition
      time in SSNMR. To this end, high-resolution solid-state (13)C CPMAS experiments
      were conducted on type I collagen (bovine tendon), bovine cortical bone, and
      demineralized bovine cortical bone, each in powdered form, to measure the (1)H
      T(1) values in the absence and in the presence of 30 mM Cu(II)(NH(4))(2)EDTA. Our
      results show that the (1)H T(1) values were successfully reduced by a factor of
      2.2, 2.9, and 3.2 for bovine cortical bone, type I collagen, and demineralized
      bone, respectively, without reducing the spectral resolution and thus enabling
      faster data acquisition. In addition, paramagnetic quenching of particular (13)C
      NMR resonances on exposure to Cu(2+) ions in the absence of mineral was also
      observed, potentially suggesting the relative proximity of three main amino acids
      in the protein backbone (glycine, proline, and alanine) to the bone mineral
      surface.

PMID- 22953758
TI  - Efficacy of cilostazol on uncontrolled coronary vasospastic angina: a pilot
      study.
AB  - BACKGROUND: Although an angina attack by vasospastic angina (VSA) can usually be
      relieved or controlled with nitrates and calcium channel blockers (CCBs), there
      are some patients who cannot be controlled even by higher doses and combinations
      of these drugs. Cilostazol is a selective inhibitor of phosphodiesterase 3 that
      increases intracellular cyclic adenosine monophosphate (cAMP) contents. A
      stimulation of cAMP signal transduction increases coronary nitric oxide
      production. We examined whether cilostazol improved angina symptoms in patients
      with VSA uncontrolled by conventional treatment. METHODS: This study was
      conducted in a prospective, multicenter, nonrandomized manner. The subject
      consisted of 21 patients (13 men, 57 +/- 9 year-old) who were diagnosed with VSA
      and had at least two angina attacks during the past 1 week despite of
      conventional medications such as CCBs and/or nitrates. They took cilostazol 100
      mg twice daily for 2 weeks in addition to the conventional medications. The
      patients recorded the frequency of angina attack and wrote down the numeric
      rating scale of a "severity of angina attack" while taking conventional
      medications and cilostazol for 2 weeks, and also recorded an averaged scale or
      total number of event during the last week at the time of the assessment. Using
      the Wilcoxon rank-sum test, we compared the changes in the scores of frequency
      and severity of angina attack before and after adding cilostazol to the
      conventional medications. RESULTS: After adding cilostazol to the conventional
      medications, there were 78.9% relative reduction of the score of angina intensity
      and 73.5% of angina frequency (P < 0.001). There were four patients (19%) who
      were forced to stop cilostazol due to headache as an adverse event. CONCLUSIONS:
      Cilostazol appears to be an effective therapy in VSA uncontrolled with
      conventional medical treatment. A further prospective, randomized, placebo
      controlled study will be needed to validate this result.

PMID- 22953759
TI  - Genetic factors account for half of the phenotypic variance in liability to sleep
      related bruxism in young adults: a nationwide Finnish twin cohort study.
AB  - OBJECTIVES: The aim of the present study was to examine the role of genetic and
      environmental factors in the phenotypic variance of bruxism in a large population
      based cohort of young adult twins in Finland. METHODS: The material of the
      present study derives from the FinnTwin16 cohort study consisting of five birth
      cohorts of twin pairs born in 1975-1979 who completed a questionnaire (at mean
      age 24, range 23-27 years) with data on frequency of sleep-related bruxism in
      2000-2002. We used quantitative genetic modeling, based on the genetic similarity
      of monozygotic and dizygotic twins, to estimate the most probable genetic model
      for bruxism, based on decomposition of phenotypic variance into
      components:additive genetic effects (A), dominant genetic effects (D), and non
      shared environmental effects (E). RESULTS: On average, 8.7% experienced bruxism
      weekly, 23.4% rarely, and 67.9% never, with no significant gender difference (p =
      .052). The best fitting genetic model for bruxism was the AE-model. Additive
      genetic effects accounted for 52% (95% Cl 0.41--0.62) of the total phenotypic
      variance. Sex-limitation model revealed no gender differences. CONCLUSIONS:
      Genetic factors account for a substantial proportion of the phenotypic variation
      of the liability to sleep-related bruxism, with no gender difference in its
      genetic architecture.

PMID- 22953760
TI  - Mechanism of perfluorooctanesulfonate (PFOS)-induced apoptosis in the immunocyte.
AB  - As a new type of persistent organic pollutant, perfluorooctane sulfonate (PFOS)
      has raised great concern in recent years due to its ubiquitous distribution in
      the general environment and its long elimination half-life in humans. PFOS has
      toxic and carcinogenic effects in animals and humans, but the effects of PFOS on
      apoptosis are still not clear. The present study aimed to determine the mode of
      cell death and its mechanism in splenocytes and thymocytes from adult male
      C57BL/6 mice administered 0, 1, 5, or 10 mg PFOS/kg/day by gavage daily for 7
      days. The results showed that more apoptotic cells were present in PFOS-treated
      mice than in control mice. PFOS induced production of reactive oxygen species
      (ROS), dissipation of mitochondria membrane potential, and apoptosis of
      splenocytes and thymocytes. Moreover, activities of superoxide dismutase,
      catalase, and glutathione reductase were increased, whereas activities of
      glutathione-S-transferase and glutathione peroxidase were decreased, in
      splenocytes. Glutathione contents were reduced as well. Differential expressions
      of proteins such as p53, Bax, caspase-3, and caspase-9 were significantly up
      regulated in PFOS-exposed hosts, whereas Bcl-2 expression was significantly down
      regulated. One possible mechanism for the findings here was that PFOS could
      overwhelm homeostasis of anti-oxidative systems, boost ROS generation, impact on
      mitochondria, and affect protein expression of apoptotic regulators, the latter
      of which resulted in initiation of the apoptosis program. Results from this study
      may provide a new insight into the potential adverse effects of PFOS exposure on
      humans, at the cellular level.

PMID- 22953761
TI  - Genome-wide gene expression profiling of introgressed indica rice alleles
      associated with seedling cold tolerance improvement in a japonica rice
      background.
AB  - BACKGROUND: Rice in tropical and sub-tropical areas is often subjected to cold
      stress at the seedling stage, resulting in poor growth and yield loss. Although
      japonica rice is generally more cold tolerant (CT) than indica rice, there are
      several favorable alleles for CT exist in indica that can be used to enhance CT
      in rice with a japonica background. Genome-wide gene expression profiling is an
      efficient way to decipher the molecular genetic mechanisms of CT enhancement and
      to provide valuable information for CT improvement in rice molecular breeding. In
      this study, the transcriptome of the CT introgression line (IL) K354 and its
      recurrent parent C418 under cold stress were comparatively analyzed to explore
      the possible CT enhancement mechanisms of K354. RESULTS: A total of 3184
      differentially expressed genes (DEGs), including 195 transcription factors, were
      identified in both lines under cold stress. About half of these DEGs were
      commonly regulated and involved in major cold responsive pathways associated with
      OsDREB1 and OsMyb4 regulons. K354-specific cold-induced genes were functionally
      related to stimulus response, cellular cell wall organization, and microtubule
      based movement processes that may contribute to increase CT. A set of genes
      encoding membrane fluidity and defensive proteins were highly enriched only in
      K354, suggesting that they contribute to the inherent CT of K354. Candidate gene
      prediction based on introgressed regions in K354 revealed genotype-dependent CT
      enhancement mechanisms, associated with Sir2, OsFAD7, OsWAK112d, and programmed
      cell death (PCD) related genes, present in CT IL K354 but absent in its recurrent
      parent C418. In K354, a number of DEGs were co-localized onto introgressed
      segments associated with CT QTLs, providing a basis for gene cloning and
      elucidation of molecular mechanisms responsible for CT in rice. CONCLUSIONS:
      Genome-wide gene expression analysis revealed that genotype-specific cold induced
      genes and genes with higher basal expression in the CT genotype contribute
      jointly to CT improvement. The molecular genetic pathways of cold stress
      tolerance uncovered in this study, as well as the DEGs co-localized with CT
      related QTLs, will serve as useful resources for further functional dissection of
      the molecular mechanisms of cold stress response in rice.

PMID- 22953763
TI  - High-performance nanosensors based on plasmonic Fano-like interference: probing
      refractive index with individual nanorice and nanobelts.
AB  - We propose two different configurations for which the Fano-like interference of
      longitudinal plasmon resonances occurring at individual metallic nanoparticles
      can be easily employed in refractive index sensing: a colloidal suspension of
      nanospheroids (nanorice) and a single nanowire with rectangular cross section
      (nanobelt) on top of a dielectric substrate. We numerically study the performance
      of the two in terms of their figures of merit, which are calculated under
      realistic conditions. For the case of nanorice, we explicitly incorporate the
      effect of size dispersity into the simulations. Our obtained results show that
      the application of the proposed configurations seems to be not only feasible but
      also very promising.

PMID- 22953762
TI  - Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine
      delivery.
AB  - We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified
      with d-octaarginine, which is a typical cell-penetrating peptide, as a carrier
      for mucosal vaccine delivery. Mice were nasally inoculated four times every
      seventh day with PBS containing ovalbumin with or without the d-octaarginine
      linked polymer. The polymer enhanced the production of ovalbumin-specific
      immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the
      nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells
      appeared to stimulate IgA production. Ovalbumin transferred to systemic
      circulation possibly enhanced IgG production. An equivalent dose of the cholera
      toxin B subunit (CTB), which was used as a positive control, was superior to the
      polymer in enhancing antibody production; however, dose escalation of the polymer
      overcame this disadvantage. A similar immunization profile was also observed when
      ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a
      vaccine-specific immune response identical to that induced by CTB, irrespective
      of the antibody type, when its dose was 10 times that of CTB. Our cell
      penetrating peptide-linked polymer is a potential candidate for antigen carriers
      that induce humoral immunity on the mucosal surface and in systemic circulation
      when nasally coadministered with antigens.

PMID- 22953764
TI  - Uncovering the FUTREX-6100XL prediction equation for the percentage body fat.
AB  - Based on the near infra-red (NIR) interactance method, the FUTREX company has
      developed a series of instruments, for the estimation of the body fat percentage
      (%BF). %BF is estimated through prediction equations incorporated in the
      instruments, which for the newest models (FUTREX-6100XL and FUTREX-6100A/ZL) are
      proprietary and they are not published anywhere. This missing knowledge may lead
      to several misunderstandings and confusion and degrades those instruments to
      'black boxes'. The present work uncovers and presents the prediction equation of
      FUTREX-6100/XL and discusses the contribution of each term of that equation to
      the %BF. Furthermore, this study presents the method used, which can be used to
      uncover equations incorporated in other instruments. This method is based on the
      idea of firstly uncovering the dependence of the equation on each parameter
      separately and then combining those dependencies to uncover the unknown equation.

PMID- 22953765
TI  - Where's the evidence? Over-the-counter medicines and pharmacy practice.

PMID- 22953766
TI  - A community pharmacy-based cardiovascular screening service: views of service
      users and the public.
AB  - OBJECTIVES: To determine whether pharmacy-based cardiovascular disease (CVD)
      screening reached the desired population, the local population's awareness of
      pharmacy screening and the views of service users and the general public about
      CVD screening. METHODS: Pharmacy staff, located in one English Primary Care Trust
      providing a CVD screening service, issued questionnaires to service users who had
      undergone screening. Face-to-face street surveys were conducted with members of
      the general public within the vicinity of each participating pharmacy. KEY
      FINDINGS: A total of 259 people were screened within the first 6 months of
      service provision, 97 of whom (37.4%) completed the evaluation questionnaire. In
      addition, 261 non-service users participated in street surveys. Most respondents
      among both service users and non-users had at least one risk factor for
      cardiovascular disease, including smoking and lack of exercise. Responses to
      statements regarding CVD screening showed a high level of agreement with the need
      for screening in both groups. However, significantly more service users (90.7%)
      agreed that a pharmacy was a good place for screening compared to the non-users
      (77.4%; P < 0.005). Likewise significantly fewer service users agreed that
      screening should be only carried out by doctors (10.3 compared to 25.3% of non
      users; P < 0.005). The overall majority of service users 96 (99.7%) had a
      positive experience of the screening service, agreeing that they were given
      enough time and pharmacists made them feel at ease. Only 9% of non-users were
      aware of the pharmacy service and, although the majority (78.4%) were willing to
      be screened at a pharmacy, this was significantly lower among males than females
      (69.9 compared to 82.7%; P < 0.005). Perceived concerns about confidentiality and
      lack of privacy were among barriers identified to taking up screening.
      CONCLUSION: Pharmacy-based CVD screening is acceptable to the public. Its uptake
      could be improved through increased awareness of the service and by addressing
      concerns about privacy and confidentiality in promotional activities.

PMID- 22953767
TI  - Older patient, physician and pharmacist perspectives about community pharmacists'
      roles.
AB  - OBJECTIVES: To investigate older patient, physician and pharmacist perspectives
      about the role of pharmacists in pharmacist-patient interactions. METHODS: Eight
      focus-group discussions were held in senior centres, community pharmacies and
      primary care physician offices. Participants were 42 patients aged 63 years and
      older, 17 primary care physicians and 13 community pharmacists. Qualitative
      analysis of the focus-group discussions was performed. KEY FINDINGS: Participants
      in all focus groups indicated that pharmacists are a good resource for basic
      information about medications. Physicians appreciated pharmacists' ability to
      identify drug interactions, yet did not comment on other specific aspects related
      to patient education and care. Physicians noted that pharmacists often were
      hindered by time constraints that impeded patient counselling. Both patient and
      pharmacist participants indicated that patients often asked pharmacists to expand
      upon, reinforce and explain physician-patient conversations about medications, as
      well as to evaluate medication appropriateness and physician treatment plans.
      These groups also noted that patients confided in pharmacists about medication
      related problems before contacting physicians. Pharmacists identified several
      barriers to patient counselling, including lack of knowledge about medication
      indications and physician treatment plans. CONCLUSIONS: Community-based
      pharmacists may often be presented with opportunities to address questions that
      can affect patient medication use. Older patients, physicians and pharmacists all
      value greater pharmacist participation in patient care. Suboptimal information
      flow between physicians and pharmacists may hinder pharmacist interactions with
      patients and detract from patient medication management. Interventions to
      integrate pharmacists into the patient healthcare team could improve patient
      medication management.

PMID- 22953768
TI  - An exploratory study of primary care pharmacist-led epilepsy consultations.
AB  - OBJECTIVE: Most epilepsies are managed with anti-epileptic drugs (AEDs), but
      medication non-adherence has been frequently reported. Satisfying patient
      information needs has demonstrated improved adherence. Multi-professional working
      has been encouraged to provide cost-effective health services by using the most
      appropriate healthcare professional. Research has demonstrated that pharmacist
      led consultations are acceptable to patients with other medical conditions and
      therefore may be appropriate for patients with epilepsy. We aimed to determine
      the feasibility and acceptability of a pharmacist-led epilepsy consultation
      (PLEC) study. This encompassed estimating the eligibility and consent rate for a
      PLEC study, plus the acceptability of potential intervention outcome measures and
      likely effects. METHODS: Eligible patients with a diagnosis of epilepsy and
      prescribed AEDs were invited by telephone to attend a PLEC. Baseline adherence,
      general mental well-being, epilepsy-related quality of life and satisfaction with
      information received about epilepsy medication were recorded. The intervention
      was a 30 min consultation to provide participants with an opportunity to ask
      questions related to their epilepsy therapy. Baseline data collection was
      repeated after 2 months. RESULTS: Of 106 (97.2%) consenting patients, 82 (77.4%)
      attended the PLEC. The 2 month follow-up questionnaire was fully completed by 50
      (67.6%) participants. The number (percentage +/- 95% confidence interval) of
      participants reporting adherent behaviour pre-PLEC was 22 (44.0 +/- 13.7%) which
      increased to 30 (60 +/- 13.6%) post-PLEC (P < 0.03, McNemar test). DISCUSSION:
      Accepting the limitations of a before-and-after study and small sample size, the
      findings suggest that a PLEC may improve adherence. A definitive trial is
      necessary to confirm the effect of a PLEC and establish the longevity and cost
      effectiveness of the outcomes. Attrition of potential participants not
      contactable by telephone suggests the need for additional postal contact in
      subsequent trials. A reduction in loss to follow-up is also desirable and
      potentially achievable using telephone reminders.

PMID- 22953769
TI  - Management of long-term hypothyroidism: a potential marker of quality of
      medicines reconciliation in the intensive care unit.
AB  - OBJECTIVE: Significant errors can be made during medication prescribing,
      dispensing and administration. One source of error and potential for harm is
      unintentional omission. Medicines reconciliation seeks to reduce the impact of
      this between transfer of care. In long-term hypothyroidism, patients are
      dependent upon levothyroxine and there are few contraindications to its
      prescription. We considered levothyroxine prescription in long-term
      hypothyroidism as a marker of medicines reconciliation on admission and during
      stay in the intensive care unit (ICU). METHODS: A retrospective chart review was
      undertaken in a tertiary referral university ICU with all patients who were
      receiving long-term levothyroxine therapy identified. Notes were reviewed for the
      presence of thyroid-replacement prescription and for thyroid function tests, in
      addition to demographic, length of stay and mortality data. KEY FINDINGS: Thyroid
      replacement therapy was not prescribed for more than 7 days in 23/133 (17.3%)
      patients and omitted entirely in three patients. A further 28/133 (21.1%)
      patients were intolerant of enteral feeding for more than 7 days and were thus
      unable to have oral levothyroxine administered. None of these patients received
      parenteral therapy. Thyroid function tests were performed in 104/133 (78.2%)
      patients. CONCLUSIONS: Prescription of chronic therapy, in this case thyroid
      replacement therapy, was inadequate. This highlights the need for a progressive
      medicines-reconciliation process embedded within the daily ICU programme.

PMID- 22953770
TI  - A systematic review of simulated-patient methods used in community pharmacy to
      assess the provision of non-prescription medicines.
AB  - OBJECTIVE: To explore the use of simulated-patient methods in community pharmacy
      for non-prescription medicines. METHODS: The databases IPA (International
      Pharmaceutical Abstracts), EMBASE and MEDLINE were searched for articles
      published between 1990 and 2010 outlining studies using simulated-patient
      methods. KEY FINDINGS: Thirty studies from 31 articles were reviewed. The
      majority used simulated-patient methods to purely assess counselling behaviour of
      pharmacy staff, rather than as an opportunity to provide educational feedback to
      improve counselling behaviour. CONCLUSIONS: Few simulated-patient studies have
      incorporated performance feedback to encourage behavioural change and improve
      counselling skills. Studies that incorporated feedback did not provide sufficient
      detail, and few studies have explored participant perceptions. Additionally, very
      few studies have employed scenarios involving children's medicines. Future
      studies should test the feasibility of using the simulated-patient method, with
      appropriate performance feedback and describe participant perceptions of the
      value and acceptability of this training method.

PMID- 22953771
TI  - Why UK pharmacy must adapt to the increasing demands of professionalism in
      practice.
AB  - OBJECTIVE: To make a case for why UK pharmacy must adapt to the increasing
      demands of professionalism in practice. METHODS: A review based on evidence from
      the literature and personal opinion. KEY FINDINGS: Pharmacists, just as with
      other occupational groups, have over the years been developing and fine-tuning
      ways through which they can attain full professional status and therefore command
      the same level of recognition and respect as the main traditional professions,
      notably medicine and law. Many commentators, however, believe that this ambition
      is far from being realised. Their argument is that the path to professional
      status is not that easily available to all occupations. Although there is a
      professionalisation process that the traditional professions go through, it has
      been argued that services provided by pharmacy, beyond dispensing, can also
      promote its level of professionalism; for example, extensive counseling,
      medication therapy management, health screening, compounding or provision of
      durable medical equipment. CONCLUSIONS: As UK pharmacy and the wider UK National
      Health Service undergo changes and reconfiguration it is hoped that the creation
      of the new professional body for pharmacy (the Royal Pharmaceutical Society) will
      help pharmacy in the UK develop the ideals of professionalism.

PMID- 22953772
TI  - A review of the medication pathway in rural Queensland, Australia.
AB  - OBJECTIVES: It is well established that rural areas have compromised access to
      health services, including medication services. This paper reviews the practice
      developments for rural health professionals in relation to medication processes,
      with a focus on regulatory provisions in Queensland, Australia, and a view to
      identifying opportunities for enhanced pharmacy involvement. METHODS: Literature
      referring to 'medication/medicine', 'rural/remote', 'Australia' and
      'pharmacy/pharmacist/pharmaceutical' was identified via EBSCOhost, Ovid,
      Informit, Pubmed, Embase and The Cochrane Library. Australian Government reports
      and conference proceedings were sourced from relevant websites. Legislative and
      policy documents reviewed include drugs and poisons legislation, the National
      Medicines Policy and the Australian Pharmaceutical Advisory Council guidelines.
      KEY FINDINGS: The following developments enhance access to medication services in
      rural Queensland: (1) endorsement of various non-medical prescribers, (2)
      authorisation of registered nurses, midwives, paramedics and Indigenous health
      workers to supply medications in sites without pharmacists, (3) skill-mixing of
      nursing staff in rural areas to ease medication administration tasks, (4)
      establishment of pharmacist-mediated medication review services, (5) electronic
      transfer of medical orders or prescriptions and (6) enhanced transfer of
      medication information between metropolitan and rural, and public and private
      facilities. CONCLUSIONS: This review identified a divide between medication
      access and medication management services. Initiatives aiming to improve supply
      of (access to) medications focus on scopes of practice and endorsements for non
      pharmacist rural healthcare providers. Medication management remains the domain
      of pharmacists, and is less well addressed by current initiatives. Pharmacists'
      involvement in rural communities could be enhanced through tele-pharmacy,
      outreach support and sessional support.

PMID- 22953773
TI  - Concurrent use of complementary and alternative medicine with antiretroviral
      therapy reduces adherence to HIV medications.
AB  - OBJECTIVE: Antiretroviral therapy requires strict adherence to ensure therapeutic
      success. Concurrent use of complementary and alternative medicine (CAM) could
      alter the adherence to and thereby effectiveness of antiretroviral drugs. This
      study examined the association of CAM use with adherence to antiretroviral
      therapy (ART) and CD4 count. METHODS: The study was conducted in two HIV clinics:
      one in a semi-urban, the other in a rural area. Adherence to ART was assessed
      using the Morisky Medication Adherence Scale (MMAS). Data on type of CAM used and
      MMAS adherence were collected by patient interview and demographic; clinical data
      were collected from hospital records. RESULTS: Altogether 212 HIV patients
      participated in the exit study conducted over 3 months. Almost half (47.9%) used
      CAM concurrently with antiretroviral drugs. Dietary supplements (40.3%), healing
      systems (36.5%) and exercise (23.2%) were mainly used. The use of CAM
      significantly lowered adherence to ART (89.4% in non-CAM users versus 82.5% in
      CAM users, P = 0.01). Improvement in CD4 count was less in patients using CAM
      compared to non-CAM users although the difference was not statistically
      significant (310.5 +/- 294.0 cells/L in CAM users versus 224.5 +/- 220.0 cells/L
      in non-CAM users, P = 0.13). Patients attending the rural HIV clinic were more
      likely to use CAM compared to patients attending semi-urban hospital (chi(2) test
      = 7.0; P < 0.01). CONCLUSION: Use of CAM could lower adherence to antiretroviral
      therapy. There is need to develop protocol which could help in monitoring CAM use
      in HIV patients especially those from rural settings.

PMID- 22953774
TI  - Community pharmacists' perceptions of the skin conditions they encounter and how
      they view their role in dermatological care.
AB  - OBJECTIVES: To explore pharmacists' perceptions of the skin conditions they
      encounter, sources of postgraduate dermatological training and views of their
      role in the management of patients with skin problems. METHOD: A self-completion
      questionnaire was sent to a random sample of 3500 community pharmacists in
      England and Wales. KEY FINDINGS: Seventy-eight per cent of pharmacists felt that
      patients sought their advice on problems about dry skin on a weekly basis. A
      total of 64.8% had undertaken postgraduate training in dermatology and the
      majority agreed that they played an important role in managing patients with skin
      problems. CONCLUSION: Pharmacists routinely encounter a small number of skin
      conditions and believe they can contribute towards the care of patients with skin
      diseases.

PMID- 22953775
TI  - Ab initio QM/MM free energy simulations of peptide bond formation in the ribosome
      support an eight-membered ring reaction mechanism.
AB  - Ab initio QM/MM free-energy simulations were carried out to study the peptide
      bond formation reaction in the peptidyl transferase center of the ribosome. The
      QM part of the reaction was treated by density functional theory at the B3LYP/6
      31G* level, while the MM part including the solvent and RNA environment was
      described by molecular force field. The calculated free-energy surfaces for the
      two popular reaction mechanisms, the six- and eight-membered ring reactions,
      exhibited large energetic differences which favor the eight-membered reaction
      mechanism. The simulated quasi-transition state structures clearly indicated a
      "late" feature consistent with previous theoretical studies. Also the important
      functional role played by water molecules in the active site of the ribosome and
      its implication in ribozymic catalysis was discussed in detail.

PMID- 22953776
TI  - Trefolane A, a sesquiterpenoid with a new skeleton from cultures of the
      basidiomycete Tremella foliacea.
AB  - Trefolane A (1), an unprecedented skeleton with a 5/6/4 tricyclic ring system,
      was isolated from cultures of the basidiomycete Tremella foliacea. The structure
      was elucidated by means of spectroscopic methods and further confirmed by single
      crystal X-ray diffraction analysis. A possible biogenesis for trefolane A (1) was
      also proposed.

PMID- 22953777
TI  - Nanocarbon networks for advanced rechargeable lithium batteries.
AB  - Carbon is one of the essential elements in energy storage. In rechargeable
      lithium batteries, researchers have considered many types of nanostructured
      carbons, such as carbon nanoparticles, carbon nanotubes, graphene, and nanoporous
      carbon, as anode materials and, especially, as key components for building
      advanced composite electrode materials. Nanocarbons can form efficient three
      dimensional conducting networks that improve the performance of electrode
      materials suffering from the limited kinetics of lithium storage. Although the
      porous structure guarantees a fast migration of Li ions, the nanocarbon network
      can serve as an effective matrix for dispersing the active materials to prevent
      them from agglomerating. The nanocarbon network also affords an efficient
      electron pathway to provide better electrical contacts. Because of their
      structural stability and flexibility, nanocarbon networks can alleviate the
      stress and volume changes that occur in active materials during the Li
      insertion/extraction process. Through the elegant design of hierarchical
      electrode materials with nanocarbon networks, researchers can improve both the
      kinetic performance and the structural stability of the electrode material, which
      leads to optimal battery capacity, cycling stability, and rate capability.  This
      Account summarizes recent progress in the structural design, chemical synthesis,
      and characterization of the electrochemical properties of nanocarbon networks for
      Li-ion batteries. In such systems, storage occurs primarily in the non-carbon
      components, while carbon acts as the conductor and as the structural buffer. We
      emphasize representative nanocarbon networks including those that use carbon
      nanotubes and graphene. We discuss the role of carbon in enhancing the
      performance of various electrode materials in areas such as Li storage, Li ion
      and electron transport, and structural stability during cycling. We especially
      highlight the use of graphene to construct the carbon conducting network for
      alloy anodes, such as Si and Ge, to accelerate electron transport, alleviate
      volume change, and prevent the agglomeration of active nanoparticles. Finally, we
      describe the power of nanocarbon networks for the next generation rechargeable
      lithium batteries, including Li-S, Li-O(2), and Li-organic batteries, and provide
      insights into the design of ideal nanocarbon networks for these devices. In
      addition, we address the ways in which nanocarbon networks can expand the
      applications of rechargeable lithium batteries into the emerging fields of
      stationary energy storage and transportation.

PMID- 22953778
TI  - Charge-dependent trends in structures and vibrational frequencies of [CO-Au
      O2](q) (q = -1, 0, +1) complexes: evidence for cooperative interactions.
AB  - Charge-dependent trends in the structures, vibrational frequencies, and binding
      energies of binary [AuCO](q) and [AuO(2)](q) and ternary [O(2)AuCO](q) complexes
      (q = -1,0,+1), have been investigated using density functional theory
      calculations. Three different geometrical motifs, given descriptive names of
      "separated", "pre-reactive", and "long-range", are identified for the ternary
      complexes. For the binary systems, the general trend is that the complexes become
      more diffuse as the charge becomes more negative, having longer intermolecular
      bond distances and weaker binding energies. The trends shown by the ternary
      complexes are more complicated, and are different for the various geometrical
      motifs. However, a general trend is that there is a cooperative interaction
      involving both the CO and O(2) with the Au center, which becomes more pronounced
      as the negative charge on the complexes increases from cationic to neutral to
      anionic. This cooperative interaction leads to increased electron density on the
      O(2) moiety, as is reflected in the bond-lengths and vibrational frequencies.
      Furthermore, it is found that for the pre-reactive complexes, the role of the Au
      center is to stabilize the formation of a conjugated pi-system between the CO and
      O(2) molecules.

PMID- 22953779
TI  - Selective quenching of 2-naphtholate fluorescence by imidazolium ionic liquids.
AB  - The effect of addition of water-miscible ionic liquids (ILs), 1-butyl-3
      methylimidazolium tetrafluoroborate ([bmim][BF(4)]), 1-butyl-3-methylimidazolium
      trifluoromethanesulfonate ([bmim][OTf]), and 1-butyl-1-methylpyrrolidinium
      trifluoromethanesulfonate ([bmpyrr][OTf]), on photophysical properties of 2
      naphthol in water at various pHs is reported. Electronic absorbance behavior of 2
      naphthol dissolved in aqueous mixtures of ILs is observed to be similar to that
      found in water at different pHs. The excited-state properties, however, are
      changed dramatically as the IL is added to the milieu. The presence of
      imidazolium IL results in significant quenching of the fluorescence emission from
      2-naphtholate. On the contrary, pyrrolidinium IL does not quench the fluorescence
      from the anionic species. The quenching of 2-naphtholate fluorescence by aromatic
      imidazolium cations in aqueous IL mixtures is found to follow simple Stern-Volmer
      behavior. The aromatic imidazolium cation acts as an electron/charge acceptor
      during the quenching process where formation of a weakly fluorescent complex
      between the imidazolium cation and the excited 2-naphtholate anion possibly
      involving the acidic C2 proton of imidazolium is proposed. Because of the absence
      of such an acidic proton, the nonaromatic pyrrolidinium cation is not able to
      form a complex with the excited 2-naphtholate and cannot act as an
      electron/charge acceptor. Excited-state emission intensity decay data further
      corroborate this hypothesis as the intensity decay fits well to a single
      exponential decay with no change in recovered lifetimes as [bmpyrr][OTf] is
      added; a double-exponential decay is required to satisfactorily fit the decay
      data in the presence of [bmim][BF(4)], hinting at the presence of a weakly
      fluorescent complex. The uniqueness of ILs in affecting excited-state properties
      of the 2-naphthol system is demonstrated through comparison with NaBF(4), NaCl,
      and polyethylene glycol with an average molecular weight of 200, respectively, as
      additives.

PMID- 22953780
TI  - Immunotoxicity and allergic potential induced by topical application of dimethyl
      carbonate (DMC) in a murine model.
AB  - Dimethyl carbonate (DMC) is an industrial chemical, used as a paint and adhesive
      solvent, with the potential for significant increases in production. Using select
      immune function assays, the purpose of these studies was to evaluate the
      immunotoxicity of DMC following dermal exposure using a murine model. Following a
      28-day exposure, DMC produced a significant decrease in thymus weight at
      concentrations of 75% and greater. No effects on body weight, hematological
      parameters (erythrocytes, leukocytes, and their differentials), or immune cell
      phenotyping (B-cells, T-cells, and T-cell sub-sets) were identified. The IgM
      antibody response to sheep red blood cell (SRBC) was significantly reduced in the
      spleen but not the serum. DMC was not identified to be an irritant and evaluation
      of the sensitization potential, conducted using the local lymph node assay (LLNA)
      at concentrations ranging from 50-100%, did not identify increases in lymphocyte
      proliferation. These results demonstrate that dermal exposure to DMC induces
      immune suppression in a murine model and raise concern about potential human
      exposure and the need for occupational exposure regulations.

PMID- 22953782
TI  - Identification of cortical germ cells in adult ovaries from three phyllostomid
      bats: Artibeus jamaicensis, Glossophaga soricina and Sturnira lilium.
AB  - It is generally considered that, in mammals, the ovary is endowed with a finite
      number of oocytes at the time of birth. However, studies concerning rodents,
      lemurs and humans suggest the existence of stem cells from the germline that may
      be involved in germ-cell renewal, maintaining postnatal follicle development.
      This type of work on wild species is scarce; therefore the objective of this
      study was to determine ovarian morphology and the presence of progenitor cells
      from the germline of three species of phyllostomid bats (Artibeus jamaicensis,
      Glossophaga soricina and Sturnira lilium). The morphological characteristics of
      the ovaries and the expression of specific markers of germline cells, stem cells
      and proliferation cells were analysed. The morphology of the ovaries of the three
      bat species was similar. A polarised ovary with follicles at different stages of
      development and groups of cortical cells similar to primordial germ cells were
      observed. Immunofluorescent analysis showed that these cortical cells express
      germline, stem-cell and proliferative markers, indicating the identification of
      germ cells that could maintain pluripotency, as well as being mitotically active.
      This suggests that in the adult ovary of phyllostomid bats there may be a
      mechanism for the self-renewal of the germline.

PMID- 22953781
TI  - The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte
      differentiation and induces obesity in mice.
AB  - The environmental obesogen hypothesis proposes that exposure to endocrine
      disruptors during developmental 'window' contributes to adipogenesis and the
      development of obesity. MEHP [mono-(2-ethylhexyl) phthalate], a metabolite of the
      widespread plasticizer DEHP [di-(2-ethylhexyl) phthalate], has been found in
      exposed organisms and identified as a selective PPARgamma (peroxisome
      proliferator-activated receptor gamma) modulator. However, implication of MEHP on
      adipose tissue development has been poorly investigated. In the present study, we
      show the dose-dependent effects of MEHP on adipocyte differentiation and GPDH
      (glycerol-3-phosphate dehydrogenase) activity in the murine 3T3-L1 cell model.
      MEHP induced the expression of PPARgamma as well as its target genes required for
      adipogenesis in vitro. Moreover, MEHP perturbed key regulators of adipogenesis
      and lipogenic pathway in vivo. In utero exposure to a low dose of MEHP
      significantly increased b.w. (body weight) and fat pad weight in male offspring
      at PND (postnatal day) 60. In addition, serum cholesterol, TAG (triacylglycerol)
      and glucose levels were also significantly elevated. These results suggest that
      perinatal exposure to MEHP may be expected to increase the incidence of obesity
      in a sex-dependent manner and can act as a potential chemical stressor for
      obesity and obesity-related disorders.

PMID- 22953783
TI  - Extra-Mediterranean refugia: The rule and not the exception?
AB  - Some decades ago, biogeographers distinguished three major faunal types of high
      importance for Europe: (i) Mediterranean elements with exclusive glacial survival
      in the Mediterranean refugia, (ii) Siberian elements with glacial refugia in the
      eastern Palearctic and only postglacial expansion to Europe and (iii) arctic
      and/or alpine elements with large zonal distributions in the periglacial areas
      and postglacial retreat to the North and/or into the high mountain systems.
      Genetic analyses have unravelled numerous additional refugia both of continental
      and Mediterranean species, thus strongly modifying the biogeographical view of
      Europe. This modified notion is particularly true for the so-called Siberian
      species, which in many cases have not immigrated into Europe during the
      postglacial period, but most likely have survived the last, or even several
      glacial phases, in extra-Mediterranean refugia in some climatically favourable
      but geographically limited areas of southern Central and Eastern Europe.
      Recently, genetic analyses revealed that typical Mediterranean species have also
      survived the Last Glacial Maximum in cryptic northern refugia (e.g. in the
      Carpathians or even north of the Alps) in addition to their Mediterranean refuge
      areas.

PMID- 22953784
TI  - Liposome encapsulation of a photochemical NO precursor for controlled nitric
      oxide release and simultaneous fluorescence imaging.
AB  - Described are photochemical studies of the nitric oxide precursors, trans
      Cr(L)(ONO)(2)(+) (L = cyclam = 1,4,8,11-tetraazacyclotetradecane, CrONO, or L =
      mac = 5,7-dimethyl-6-anthracenylcyclam, mac-CrONO) encapsulated in
      phosphatidylcholine liposomes. The liposomes provide a means to maintain a
      localized high concentration of NO releasing complexes and are easily modified
      for in vivo targeting through self-assembly. Steady, controlled release of NO is
      seen after photolysis of the liposome-encapsulated CrONO as compared to the burst
      of NO release seen by the unencapsulated complex in oxygenated solutions. The
      quantum yields for photochemical NO release from liposome-encapsulated CrONO and
      mac-CrONO were determined in both oxygenated and anoxic solutions. The quantum
      yield for NO release in oxygenated solution for encapsulated CrONO was more than
      5 times larger than that of unencapsulated CrONO, thus the net NO released after
      photolysis in oxygenated solutions is enhanced by encapsulation of CrONO in
      liposomes. Encapsulated mac-CrONO shows NO release after photolysis with low
      intensity blue light. Furthermore, the fluorescence of mac-CrONO can be detected
      through the liposomes, thus allowing for development of theranostic NO delivery
      vessels where tracking and imaging can occur simultaneously with therapeutic NO
      release. This work provides insight into the development of multifunctional
      liposome constructs for disease theranostics.

PMID- 22953785
TI  - Perceptions of parents and physicians concerning the Childhood Asthma Control
      Test.
AB  - BACKGROUND: The Childhood Asthma Control Test (C-ACT) has been proposed to be a
      simple, patient-based test that is able to reflect the multidimensional nature of
      asthma control. In this analysis, the aim was to evaluate the perceptions of
      physicians and caregivers concerning C-ACT and its predictive value for future
      asthma-related events. METHOD: In a multicenter prospective design, 368 children
      aged 4-11 years with asthma who were either well- or not well-controlled were
      included in the study. The study participants were evaluated during three visits
      made at 2-month intervals and the Turkish version of C-ACT was completed each
      month. Parents completed questionnaires concerning their perception of asthma
      (before and after the study) and the C-ACT (after the study). Physicians
      completed a survey about their perception of a control-based approach and the C
      ACT. RESULTS: The C-ACT scores increased from visit 1 to visit 3, with
      improvement seen in all domains of the test. At the end of the study period, the
      parents more strongly agreed that asthma could be controlled completely and that
      asthma attacks and nocturnal awakenings due to asthma were preventable (p < .05).
      Most of the parents reported that the C-ACT helped them to determine asthma
      treatment goals for their children and also that the C-ACT improved communication
      with their physicians. The physicians indicated that a control-centered approach
      was more convenient (95%) and simpler (94.5%) than a severity-centered approach
      and provided better disease control (93.4%). A higher C-ACT score was associated
      with a decreased risk of asthma attack and emergency department admittance in the
      2 months following the administration of C-ACT. Conclusion. Our findings
      indicated that the C-ACT improved both parental outlook on asthma control and the
      communication between the physician and parents. There was a good correlation
      between the C-ACT score and the level of asthma control achieved, as described by
      the physician. Additionally the C-ACT score was predictive of future asthma
      related events. These findings suggest that the C-ACT may have an important role
      in asthma management in the future.

PMID- 22953786
TI  - Bone marrow-derived mononuclear cell therapy for patients with ischemic heart
      disease and ischemic heart failure.
AB  - OBJECTIVE: This meta-analysis aimed to assess whether bone marrow-derived
      mononuclear cells (BMMNCs) therapy may improve cardiac functional parameters in
      patients with ischemic heart disease (IHD) or ischemic heart failure (IHF).
      METHODS: Relevant randomized controlled trials (RCTs) were searched from web
      databases. Weighted mean difference was calculated for changes in left
      ventricular ejection fraction (LVEF), left ventricular end-diastolic and end
      systolic volumes by using a random effects model. RESULTS: 13 RCTs met inclusion
      criteria. Compared with controls, BMMNCs therapy improved LVEF by 3.83% (95%
      confidence interval (CI): 2.10 - 5.56%; p < 0.0001) in patients with ischemic
      heart conditions. Notably, in patients with IHF, a more severe clinical condition
      when compared with IHD, BMMNCs therapy appeared more effective in LVEF
      improvement. While LVEF increased by 5.67% (95% CI: 3.65 - 7.69%; p < 0.00001) in
      IHF patients, it only increased by 2.19% (95% CI: 0.37 - 4.00%; p = 0.02) in
      patients with IHD. CONCLUSIONS: BMMNCs therapy is associated with moderate but
      significant improvement over regular therapy in LVEF in patients with IHD and
      IHF. This observation, therefore, supports further RCTs conducting safety and
      efficiency of BMMNCs therapy with longer-term follow-up.

PMID- 22953787
TI  - A novel murine femoral segmental critical-sized defect model stabilized by plate
      osteosynthesis for bone tissue engineering purposes.
AB  - Mouse models are invaluable tools for mechanistic and efficacy studies of the
      healing process of large bone defects resulting in atrophic nonunions, a severe
      medical problem and a financial health-care-related burden. Models of atrophic
      nonunions are usually achieved by providing a highly stable biomechanical
      environment. For this purpose, external fixators have been investigated, but
      plate osteosynthesis, despite its high clinical relevance, has not yet been
      considered in mice. We hereby proposed and investigated the use of an internal
      osteosynthesis for stabilizing large bone defects. To this aim, a 3.5-mm-long
      segmental bone defect was induced in the mid-shaft of the femur using a Gigli saw
      and a jig. Bone fixation was performed using a titanium microlocking plate with
      four locking screws. The bone defect was either left empty or filled with a
      syngenic bone graft or filled with a coralline scaffold. Healing was monitored
      using radiographs. The healing process was further assessed using microcomputed
      tomography and histology 10 weeks after surgery. With the exception of one mouse
      that died during the surgical procedure, no complications were observed. A stable
      and reproducible bone fixation as well as a reproducible fixation of the
      implanted materials with full weight bearing was obtained in all animals tested.
      Nonunion was consistently observed in the group in which the defects were left
      empty. Bone union was obtained with the syngenic bone grafts, providing evidence
      that, although such defects were of critical size, bone healing was possible when
      the gold-standard material was used to fill the defect. Although new bone
      formation was greater in the coralline scaffold group than in the left-empty
      animal group, it remained limited and localized close to the bony edges, a
      consequence of the critical size of such bone defect. Our study established a
      reproducible, clinically relevant, femoral, atrophic nonunion, critical-sized
      defect, low morbidity mouse model. The present study was successful in designing
      and testing in a small animal model, a novel surgical method for the assessment
      of bone repair; this model has the potential to facilitate investigations of the
      molecular and cellular events involved in bone regeneration in load-bearing,
      segmental-bone defects.

PMID- 22953788
TI  - Nanosize storage properties in spinel Li4Ti5O12 explained by anisotropic surface
      lithium insertion.
AB  - Nanosizing is a frequently applied strategy in recent years to improve storage
      properties of Li-ion electrodes and facilitate novel storage mechanisms. Due to
      particle size reduction, surface effects increasingly dominate, which can
      drastically change the storage properties. Using density functional theory
      calculations we investigate the impact of the surface environment on the Li-ion
      insertion properties in defective spinel Li(4+x)Ti(5)O(12), a highly promising
      negative electrode material. The calculations reveal that the storage properties
      strongly depend on the surface orientation. The lowest energy (1 1 0) surface is
      predicted to be energetically favorable for Li-ion insertion into the vacant 16c
      sites. The (1 1 1) surface allows capacities that significantly exceed the bulk
      capacity Li(7)Ti(5)O(12) at voltages greater than 0 V by occupation of 8a sites
      in addition to the fully occupied 16c sites. One of the key findings is that the
      surface environment extends nanometers into the storage material, leading to a
      distribution of voltages responsible for the curved voltage profile commonly
      observed in nanosized insertion electrode materials. Both the calculated surface
      specific voltage profiles and the calculated particle size dependent voltage
      profiles are in good agreement with the experimental voltage profiles reported in
      literature. These results give a unique insight into the impact of
      nanostructuring and further possibilities of tailoring the Li-ion voltage
      profiles and capacities in lithium insertion materials.

PMID- 22953789
TI  - Venice Chart international consensus document on atrial fibrillation ablation:
      2011 update.

PMID- 22953790
TI  - Extensive pneumatosis coli misdiagnosed and mismanaged as polyposis.

PMID- 22953791
TI  - No-shows to primary care appointments: subsequent acute care utilization among
      diabetic patients.
AB  - BACKGROUND: Patients who no-show to primary care appointments interrupt
      clinicians' efforts to provide continuity of care. Prior literature reveals no
      shows among diabetic patients are common. The purpose of this study is to assess
      whether no-shows to primary care appointments are associated with increased risk
      of future emergency department (ED) visits or hospital admissions among
      diabetics. METHODS: A prospective cohort study was conducted using data from
      8,787 adult diabetic patients attending outpatient clinics associated with a
      medical center in Indiana. The outcomes examined were hospital admissions or ED
      visits in the 6 months (182 days) following the patient's last scheduled primary
      care appointment. The Andersen-Gill extension of the Cox proportional hazard
      model was used to assess risk separately for hospital admissions and ED visits.
      Adjustment was made for variables associated with no-show status and acute care
      utilization such as gender, age, race, insurance and co-morbid status. The
      interaction between utilization of the acute care service in the six months prior
      to the appointment and no-show was computed for each model. RESULTS: The six
      month rate of hospital admissions following the last scheduled primary care
      appointment was 0.22 (s.d. = 0.83) for no-shows and 0.14 (s.d. = 0.63) for those
      who attended (p < 0.0001). No-show was associated with greater risk for
      hospitalization only among diabetics with a hospital admission in the prior six
      months. Among diabetic patients with a prior hospital admission, those who no
      showed were at 60% greater risk for subsequent hospital admission (HR = 1.60, CI
      = 1.17-2.18) than those who attended their appointment. The six-month rate of ED
      visits following the last scheduled primary care appointment was 0.56 (s.d. =
      1.48) for no-shows and 0.38 (s.d. = 1.05) for those who attended (p < 0.0001);
      after adjustment for covariates, no-show status was not significantly related to
      subsequent ED utilization. CONCLUSIONS: No-show to a primary care appointment is
      associated with increased risk for hospital admission among diabetics recently
      hospitalized.

PMID- 22953793
TI  - Structure assignment of lucentamycin E and revision of the olefin geometries of
      the marine-derived lucentamycins.
AB  - A new lucentamycin analogue, lucentamycin E (5), was isolated from the culture
      broth of the marine-derived actinomycete Nocardiopsis lucentensis, strain CNR
      712. The absolute stereostructure of 5 was assigned by comprehensive analyses of
      NMR data and by application of the advanced Marfey's method. The planar structure
      of 5 was analogous to lucentamycins A-D, whereas the olefin geometry of the 3
      methyl-4-ethylideneproline moiety was found to be E, opposite of that previously
      reported. Consequently, a reinvestigation of the olefin geometries of the 3
      methyl-4-ethylideneproline residues of lucentamycins A-D showed that the olefin
      geometries of the substituted proline functionalities must be revised to
      (2S,3R,E)-3-methyl-4-ethylideneproline.

PMID- 22953792
TI  - How to improve drug dosing for patients with renal impairment in primary care - a
      cluster-randomized controlled trial.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for
      inappropriate or potentially harmful prescribing. The aim of this study was to
      examine whether a multifaceted intervention including the use of a software
      programme for the estimation of creatinine clearance and recommendation of
      individual dosage requirements may improve correct dosage adjustment of relevant
      medications for patients with CKD in primary care. METHODS: A cluster-randomized
      controlled trial was conducted between January and December 2007 in small primary
      care practices in Germany. Practices were randomly allocated to intervention or
      control groups. In each practice, we included patients with known CKD and elderly
      patients (>=70 years) suffering from hypertension. The practices in the
      intervention group received interactive training and were provided a software
      programme to assist with individual dose adjustment. The control group performed
      usual care. Data were collected at baseline and at 6 months. The outcome
      measures, analyzed across individual patients, included prescriptions exceeding
      recommended maximum daily doses, with the primary outcome being prescriptions
      exceeding recommended standard daily doses by more than 30%. RESULTS: Data from
      44 general practitioners and 404 patients are included. The intervention was
      effective in reducing prescriptions exceeding the maximum daily dose per
      patients, with a trend in reducing prescriptions exceeding the standard daily
      dose by more than 30%. CONCLUSIONS: A multifaceted intervention including the use
      of a software program effectively reduced inappropriately high doses of renally
      excreted medications in patients with CKD in the setting of small primary care
      practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02900734.

PMID- 22953794
TI  - Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective
      placebo-controlled randomized trial.
AB  - BACKGROUND: Cardiac shock wave therapy (CSWT) delivered to the myocardium
      increases capillary density and regional myocardial blood flow in animal
      experiments. In addition, nonenzymatic nitric oxide production and the
      upregulation of vascular growth factor's mRNA by CSWT have been described. The
      aim of the study was therefore to test its potential to relieve symptoms in
      patients with chronic stable angina pectoris. METHODS: Twenty-one patients (mean
      age 68.2 +/- 8.3 years, 19 males) with chronic refractory angina pectoris and
      evidence of inducible myocardial ischemia during MIBI-SPECT imaging, were
      randomized into a treatment (n = 11) and a placebo arm (n = 10). The region of
      exercise-induced ischemia was treated with echocardiographic guidance during nine
      sessions over a period of 3 months. One session of CSWT consisted of 200
      shots/spot (9--12 spots/session) with an energy intensity of 0.09 mJ/mm(2) . In
      the control group acoustic simulation was performed without energy application.
      Medication was kept unchanged during the whole treatment period. RESULTS: In the
      treatment group, symptoms improved in 9/11 patients, and the ischemic threshold,
      determined by cardiopulmonary exercise stress testing, increased from 80 +/- 28
      to 95 +/- 28 W (P= 0.036). In the placebo arm, only 2/10 patients reported an
      improvement and the ischemic threshold remained unchanged (98 +/- 23 to 107 +/-
      23 W; P= 0.141). The items "physical functioning" (P= 0.043), "general health
      perception" (P= 0.046), and "vitality" (P= 0.035) of the SF-36 questionnaire
      significantly improved in the treatment arm, whereas in the placebo arm, no
      significant change was noted. Neither arrhythmias, troponin rise nor
      complications were observed during treatment. CONCLUSIONS: This placebo
      controlled trial shows a significant improvement in symptoms, quality of life
      parameters and ischemic threshold during exercise in patients with chronic
      refractory angina pectoris treated with CSWT. Thus, CSWT represents a new option
      for the treatment of patients with refractory AP.

PMID- 22953795
TI  - Reducing strain and fracture of electrophoretically deposited CdSe nanocrystal
      films. I. Postdeposition infusion of capping ligands.
AB  - Thick electrophoretically deposited (EPD) films of ligand-capped colloidal
      nanocrystals that adhere to the substrate typically crack after they are removed
      from the deposition solvent due to the loss of residual solvent. We report the
      suppression of fracture in several micrometers thick EPD films of CdSe
      nanocrystals by treating the wet, as-deposited films with solutions containing
      the NC core-capping ligand, trioctylphosphine oxide (TOPO). The increase in TOPO
      ligand density increases photoluminescence of the dried film and leads to a
      decrease in elastic modulus.

PMID- 22953796
TI  - Synthesis of pyrrolo[2,3-b]indole via iodine(III)-mediated intramolecular
      annulation.
AB  - New synthetic procedures for the pyrrolo[2,3-b]indole skeleton have been
      developed via intramolecular annulation of indole derivatives under iodine(III).
      A series of indole derivatives with different protecting groups or substitutions
      were explored to facilitate the corresponding pyrrolo[2,3-b]indole compounds in
      excellent yields.

PMID- 22953797
TI  - Defensin protein from sweet potato (Ipomoea batatas [L.] Lam 'Tainong 57')
      storage roots exhibits antioxidant activities in vitro and ex vivo.
AB  - This study was designed to investigate the antioxidant activities of sweet potato
      defensin (SPD1) in vitro and ex vivo. Antioxidant status [2,2'-azinobis[3
      ethylbenzthiazoline-6-sulphonic acid (ABTS) assay], scavenging activity against
      DPPH (1,1-dipheny-2-picrylhydrazyl) radical method, reducing power method, Fe(2+)
      chelating ability, FTC (ferric thiocyanate) method, and protection of calf thymus
      DNA against hydroxyl radical-induced damage were studied in vitro. The ex vivo
      experiments revealed that SPD1 could decrease the production of intracellular
      peroxide in HepG2 cells. Four peptides, namely GFR, GPCSR, CFCTKPC and MCESASSK
      for testing antioxidative activity, were synthesized according to tryptic
      hydrolysis simulation. In the TEAC assay CFCTKPC performed the best (13.5+/
      0.3MUmol TE/g dw), even better than reduced glutathione (7.3+/-0.2MUmol TE/g dw).
      In the DPPH radical assay (%), [IC(50) (MUM) (the concentration required for
      scavenging 50% activity)] CFCTKPC again had the highest antioxidant activity
      (IC(50) is 11.3+/-3.2MUM) even better than reduced glutathione (IC(50) is 74.3+/
      2.4MUM). In the lipid peroxidation assay, once again CFCTKPC performed the best,
      with an IC(50) value of 0.5+/-0.0MUM better than reduced glutathione (1.2+/
      0.1MUM). These findings mean that cysteine residue is most important in
      antioxidant activities. It was suggested that SPD1 might contribute its
      antioxidant activities against hydroxyl and peroxyl radicals.

PMID- 22953798
TI  - New nitrogen-containing bromophenols from the marine red alga Rhodomela
      confervoides and their radical scavenging activity.
AB  - In addition to nine known bromophenol derivatives, five new nitrogen-containing
      bromophenols were isolated from an ethyl acetate extract of the marine red alga
      Rhodomela confervoides. By using spectroscopic methods, the structures of the new
      compounds were identified as 3-(2,3-dibromo-4,5-dihydroxybenzyl)pyrrolidine-2,5
      dione (1), methyl 4-(2,3-dibromo-4,5-dihydroxybenzylamino)-4-oxobutanoate (2), 4
      (2,3-dibromo-4,5-dihydroxybenzylamino)-4-oxobutanoic acid (3), 3-bromo-5-hydroxy
      4-methoxybenzamide (4), and 2-(3-bromo-5-hydroxy-4-methoxyphenyl)acetamide (5).
      All of these bromophenols showed potent scavenging activity against DPPH (1,1
      diphenyl-2-picrylhydrazyl) radicals, with IC(50) values ranging from 5.22 to
      23.60MUM. These compounds also displayed moderate activity against ABTS (2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulphonate) radicals, with Trolox Equivalent
      Antioxidant Capacity values (TEAC) ranging from 2.11 to 3.58mM. The results
      obtained in this study demonstrate that the bromophenols obtained from R.
      confervoides may have potential application in food and/or pharmaceutical fields
      as natural antioxidants.

PMID- 22953799
TI  - Electrochemical detection of carbamate pesticides in fruit and vegetables with a
      biosensor based on acetylcholinesterase immobilised on a composite of polyaniline
      carbon nanotubes.
AB  - A sensitive electrochemical acetylcholinesterase (AChE) biosensor was
      successfully developed on polyaniline (PANI) and multi-walled carbon nanotubes
      (MWCNTs) core-shell modified glassy carbon electrode (GC), and used to detect
      carbamate pesticides in fruit and vegetables (apple, broccoli and cabbage). The
      pesticide biosensors were applied in the detection of carbaryl and methomyl
      pesticides in food samples using chronoamperometry (CA). The GC/MWCNT/PANI/AChE
      biosensor exhibited detection limits of 1.4 and 0.95MUmolL(-1), respectively, for
      carbaryl and methomyl. These detection limits were below the allowable
      concentrations set by Brazilian regulation standards for the samples in which
      these pesticides were analysed. Reproducibility and repeatability values of 2.6%
      and 3.2%, respectively, were obtained in the conventional procedure. The proposed
      biosensor was successfully applied in the determination of carbamate pesticides
      in cabbage, broccoli and apple samples without any spiking procedure. The
      obtained results were in full agreement with those from the HPLC procedure.

PMID- 22953800
TI  - Multi-elemental composition and physical properties of honey samples from
      Malaysia.
AB  - The elemental profiles of six honey samples from Malaysia had been constructed
      using the data obtained from both ICP-AES and ICP-MS. Potassium and sodium were
      the most abundant minerals covering from 69.3-78.6% and 14.1-28.7%, respectively.
      The ratio of potassium to sodium was more than one. Even though the minerals and
      trace elements composition varied dependent on the type of honey samples, there
      was no statistically significant difference between the analysed honey samples,
      namely tualang, gelam, acacia and a few forest honeys based on two-factor ANOVA
      and cluster analysis. The total element content of honey samples were strongly
      correlated with the electrical conductivity, but only have moderate correlation
      with the ash content and honey colour based on the regression analysis. PCA
      result on the available elemental data from worldwide honeys, including honey
      samples from Malaysia revealed that potassium and sodium were the mineral markers
      to distinguish honey origin. Both tualang and gelam honey samples from Malaysia
      have close mineral profile with sesame honeys from Egypt and multifloral honeys
      from India, whereas forest honeys Malaysia were near to avocado honeys from Spain
      and multifloral honeys from India.

PMID- 22953801
TI  - A disposable amperometric immunosensor for chlorpyrifos-methyl based on
      immunogen/platinum doped silica sol-gel film modified screen-printed carbon
      electrode.
AB  - A disposable amperometric immunosensor for sensitive detection of chlorpyrifos
      methyl (CM) has been developed by combining dual signal amplification of platinum
      colloid with an enzymatic catalytic reaction. The immunosensor was fabricated by
      modification of the screen-printed carbon electrodes (SPCE) with nanocomposites
      made by skillful doping of bovine serum albumin conjugated chlorpyrifos-methyl
      antigen (BSA-Ag) and platinum colloid into silica sol-gel. The scanning electron
      microscope (SEM) images and electrochemical measurements showed that platinum
      colloid domains in the nanocomposite material could enhance electron transfer and
      change the brittleness of the silica sol-gel. The immobilisation of BSA-Ag on the
      nanocomposite retained its immunoactivities, which allowed the immobilised BSA-Ag
      to effectively capture unbound Ab-HRP in the detection solution. A linear
      response to CM concentration was exhibited, ranging from 0.4 to 20ng/mL.
      Detection of CM with the presented method in soil or grape samples treated with
      CM matched the reference values well, which indicated that the proposed
      disposable immunosensor hold promising applications in environmental and food
      monitoring.

PMID- 22953802
TI  - Spectrofluorimetric determination of ellagic acid in brandy.
AB  - Two spectrofluorimetric methods have been developed for the rapid determination
      of ellagic acid. The first method is based on the complex formation between
      ellagic acid and borax in methanol solution. The fluorescence of the complex is
      monitored at an emission wavelength of 456nm with excitation at 383nm. Linear
      calibration curve was obtained from 2.5*10(-8) to 7.5*10(-7)molL(-1) and the
      limit of determination was 4*10(-9)molL(-1). The second method is based on the
      complex formation between ellagic acid and boric acid in ethanol solution. The
      fluorescence of the complex is monitored at an emission wavelength of 447nm with
      excitation at 387nm. Linear calibration curve was obtained from 1.25*10(-7) to
      1.00*10(-6)molL(-1) and the limit of determination was 7*10(-9)molL(-1). The
      methods were successfully applied for the determination of ellagic acid in brandy
      samples. The results were found to be in good agreement with those obtained by
      HPLC method.

PMID- 22953803
TI  - Classification of Spanish DO white wines according to their elemental profile by
      means of support vector machines.
AB  - Spanish white wines from four production areas protected by Appellation Control
      laws have been analysed by inductively coupled plasma optical emission
      spectrometry to determine the contents of aluminium, barium, boron, calcium,
      chromium, copper, iron, magnesium, manganese, nickel, phosphorous, potassium,
      silicon, sodium, strontium, sulphur and zinc. These elements were used as
      chemical descriptors in order to differentiate wines from different brands
      certified of origin. Kruskal-Wallis test was applied to highlight significant
      differences between the four considered classes and pattern recognition methods
      were applied to construct classification models. In this way, principal component
      analysis was used to visualise data trends and backward stepwise linear
      discriminant analysis was applied in order to reduce the number of input
      variables. The concentrations of chromium, manganese, silicon, sodium and
      strontium were used to construct a support vector machine classification model,
      obtaining a 100% of classification performance.

PMID- 22953804
TI  - Combined effects of high-pressure and enzymatic treatments on the hydrolysis of
      chickpea protein isolates and antioxidant activity of the hydrolysates.
AB  - A chickpea protein isolate (CPI) was pretreated before hydrolysis under a
      pressure that varied between 100 and 600MPa. The hydrolysis rate increased
      significantly with pressure above 300MPa. At 40min, the DH of the control was
      15.3%, while the DH of the CPI treated at 300MPa was 18.5%, which reached 23.74%
      post treatment at 400MPa. The pretreatment of CPI above 300MPa enhanced the
      superoxide anion capturing rate of enzymatic hydrolysis. Pretreatment at 400MPa
      significantly reduced the hydrolysis time with the release of antioxidant
      peptides. While hydrolysis by Alcalase during treatment at high pressure (100
      300MPa) significantly increased the degree of hydrolysis (DH), its maximum value
      peaked after hydrolysis at 200MPa for 30min. In addition, hydrolysates obtained
      at high pressure (100-300MPa) had a higher superoxide anion capturing rate. High
      pressure treatment at 200MPa for 20min resulted in products with high
      antioxidative activity. The molecular-weight (MW) determination of the enzymatic
      hydrolysates indicated that hydrolysis at high pressure could significantly
      increase the amount of low-molecular-weight peptides.

PMID- 22953805
TI  - Analytical comparison and sensory representativity of SAFE, SPME, and Purge and
      Trap extracts of volatile compounds from pea flour.
AB  - Pisum sativum is of great economic and nutritional interest due to its protein
      content. Nevertheless, pea products are underused as a protein source in human
      food because of their strong beany flavour. Therefore, the objective of this
      study was to select an efficient and representative method to extract volatile
      molecules of pea flour. In the first step, three extraction methods were chosen:
      solid phase micro extraction (SPME); Purge and Trap extraction and solvent
      assisted flavour evaporation (SAFE). The corresponding extracts were analysed by
      gas chromatography coupled with mass spectrometry. In the second step, the
      sensory representativity of the extracts was assessed either by direct gas
      chromatography-olfactometry for SPME and for Purge and Trap extracts, or by
      sniffing for the aqueous SAFE extract. It appeared that SAFE extraction was the
      most suitable method because of its good extraction capacities and its high
      sensory representativity of the global odour of pea flour.

PMID- 22953806
TI  - Changes in Maillard reaction products in ghee during storage.
AB  - Ghee (milkfat from heat clarification) was made using direct cream (DC), cream
      butter (CB) or pre-stratification (PS) methods and stored at 60 degrees C, in
      air, for at least two weeks. Milkfat degradation, particularly oxidation,
      occurred in all types of ghee, resulting in increases in aldehydes and free fatty
      acids. However, there was little difference in fat degradation rates in each type
      of ghee. DC and CB ghee contained volatile Maillard reaction products, whereas PS
      ghee did not. The concentrations of 3,4-dihydroxy-3-hexen-2,5-dione (DHHD) and
      2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (pyranone), Maillard reaction
      products found in DC and CB ghee, rapidly decreased during storage, associated
      with increases in acetic acid. This work suggests hydration of both DHHD and
      pyranone, during storage, could form reactive 1-deoxy-d-erythro-hexo-2,3-diulose
      (1-deoxyglucosone) that degrades mostly to acetic acid. Thus, the Maillard
      reaction cascade appears to continue in food, in the absence of proteins and
      sugars, long after cooking has ceased.

PMID- 22953807
TI  - Berry components inhibit alpha-glucosidase in vitro: synergies between acarbose
      and polyphenols from black currant and rowanberry.
AB  - Polyphenol-rich extracts from certain berries inhibited alpha-glucosidase
      activity in vitro. The two most effective berry extracts, from black currant and
      rowanberry, inhibited alpha-glucosidase with IC(50) values respectively of 20 and
      30MUg GAE/ml and were as effective as the pharmaceutical inhibitor, acarbose.
      These berry extracts differed greatly in their polyphenol composition: black
      currant was dominated by anthocyanins (~70% of total) whereas rowanberry was
      enriched in chlorogenic acids (65% total) and had low levels of anthocyanins.
      Both black currant and rowanberry extracts potentiated the inhibition caused by
      acarbose and could replace the inhibition lost by reducing the acarbose dose.
      However, no additive effects were noted when black currant and rowanberry
      extracts were added in combination. The mechanisms underlying the synergy between
      acarbose and the berry polyphenols and the lack of synergy between the berry
      components are discussed. These extracts exhibited the potential to replace
      acarbose (or reduce the dose required) in its current clinical use in improving
      post-prandial glycaemic control in type 2 diabetics. As a result, these
      polyphenols may offer a dietary means for type 2 diabetics to exercise glycaemic
      control.

PMID- 22953808
TI  - Evaluation of polycyclic aromatic hydrocarbons content in different stages of
      soybean oils processing.
AB  - A study was conducted in order to determine the levels of 13 polycyclic aromatic
      hydrocarbons (PAHs) in crude soybean oils produced in Brazil and to evaluate the
      influence of the refining process in their reduction. Analysis of intermediary
      products (neutralized, bleached and deodorized oils) showed that all compounds
      were reduced through refining (up to 88%). Neutralization and deodorization steps
      contributed effectively to the PAHs decrease. The mean total PAHs content in
      crude and deodorized oil samples ranged, respectively, from 10 to 316 and 3 to
      69MUg/kg. Since vegetable oils have been shown to be the major sources of PAHs in
      the diet, a monitoring program should be developed by the refining industries and
      the use of activated carbon during oil processing is highly recommended.

PMID- 22953809
TI  - High antioxidant activity of coffee silverskin extracts obtained by the treatment
      of coffee silverskin with subcritical water.
AB  - Coffee silverskin (CS) is a thin tegument of the outer layer of green coffee
      beans and a major by-product of the roasting process to produce roasted coffee
      beans. CS extracts obtained by the treatment of CS with subcritical water at 25
      270 degrees C were investigated for their antioxidant activity using hydrophilic
      oxygen radical absorption capacity (H-ORAC) and DPPH radical scavenging capacity
      assays. The antioxidant activity increased with increasing the extraction
      temperature and the highest activity was observed with the extracts obtained at
      270 degrees C. The H-ORAC and DPPH values of the extracts were 2629+/-193 and
      379+/-36MUmol TE/g of CS extract, respectively. High correlation (R=0.999) was
      observed between H-ORAC and DPPH values for the CS extracts. High correlation of
      the antioxidant activity was also observed with protein and phenolic contents in
      the extracts. The CS extracts could be useful as a good source of antioxidative
      materials.

PMID- 22953810
TI  - Germinated grains--sources of bioactive compounds.
AB  - Germination of seven selected commercially important grains was studied to
      establish its effects on the nutritional and chemical composition. The changes in
      the concentration of the nutrients, bioactive compounds and the inhibitory effect
      of extracts on alpha-glucosidase and alpha-amylase activities were investigated.
      These were measured through proximate analysis, inhibition assays and HPLC.
      Germinated sorghum and rye extracts inhibited (p<0.05) alpha-glucosidase
      activity, whereas barley and sorghum extracts exhibited higher inhibitory
      activities against alpha-amylase. Germinated grains contained substantial amounts
      of total phenolics with rye having significantly higher content compared with the
      non-germinated grains. Radical scavenging activities of the phenolic extracts
      were between 13% and 73% for non-germinated and 14% and 53% for germinated.
      Inositol phosphate (InsP) 4, 5 and 6 were noted in all the grains, but InsP 6 was
      significantly lower in concentration. This study indicates the potential of
      germinated barley, sorghum and rye for the development of effective
      physiologically bioactive compounds for the reduction of the risk of diabetic
      agents and colon cancer.

PMID- 22953811
TI  - Six cytotoxic annonaceous acetogenins from Annona squamosa seeds.
AB  - Custard apple (Annona squamosa L.) is an edible tropical fruit, and its seeds had
      been used in south China as a folk medicine to treat "malignant sore" (cancer)
      and as an insecticide. Phytochemical investigation of the ethanol fraction of
      custard apple seeds led to the isolation of six new annonaceous acetogenins:
      annosquacins A-D (1-4), annosquatin A (5) and annosquatin B (6). Their structures
      were elucidated by spectroscopic analysis. Compounds 1-4 are adjacent
      bistetrahydrofuran annonaceous acetogenins. Compounds 5 and 6 are non-adjacent
      bistetrahydrofuran annonaceous acetogenins and the first examples in which the
      tetrahydrofuran ring system is located between C-9 and C-20. The absolute
      configurations of 1-6 were defined by the application of the Mosher method.
      Compounds 1-6 exhibited potent cytotoxic activity in vitro against five human
      tumour cell lines. Compounds 5 and 6 showed a high selectivity toward the MCF-7
      and A-549 cell line respectively.

PMID- 22953812
TI  - Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced
      production of nitric oxide and pro-inflammatory cytokines via the inactivation of
      nuclear factor-kappaB and p38 mitogen-activated protein kinase in RAW264.7
      macrophages.
AB  - It has been reported that fucosterol has anti-diabetic, anti-oxidant, and anti
      osteoporotic effects. We investigated the anti-inflammatory effects and the
      underlying molecular mechanism of fucosterol in lipopolysaccharide (LPS)-induced
      RAW 264.7 macrophages. Fucosterol suppressed the expressions of inducible nitric
      oxide synthase (iNOS), tumour necrosis factor-alpha (TNF-alpha), and interleukin
      6 (IL-6) by downregulating their transcriptions, and subsequently inhibited the
      productions of nitric oxide, TNF-alpha, and IL-6. In addition, fucosterol
      attenuated LPS-induced DNA binding and the transcriptional activity of nuclear
      factor-kappaB (NF-kappaB). These reductions were accompanied by parallel
      reductions in the phosphorylation and nuclear translocation of NF-kappaB.
      Furthermore, fucosterol attenuated the phosphorylations of mitogen-activated
      protein kinase kinases 3/6 (MKK3/6) and mitogen-activated protein kinase
      activated protein kinase 2 (MK2), which are both involved in the p38 MAPK
      pathway. These results suggest that the anti-inflammatory effects of fucosterol
      are associated with the suppression of the NF-kappaB and p38 MAPK pathways.

PMID- 22953813
TI  - Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) extract and
      its bioactive components suppress Propionibacterium acnes-induced inflammation.
AB  - In this study, we aimed to evaluate the inhibitory effect of wild bitter melons
      (WBM; Momordica charantia Linn. var. abbreviata Ser.) on Propionibacterium acnes
      induced inflammation and to identify the bioactive components. Our results showed
      that ethyl acetate (EA) extract of WBM fruit in vitro potently suppressed pro
      inflammatory cytokine and matrix metalloproteinase (MMP)-9 levels in P. acnes
      stimulated THP-1 cells. Furthermore, concomitant intradermal injection of WBM EA
      extract in mice effectively attenuated P. acnes-induced ear swelling and
      granulomatous inflammation. To further investigate the bioactive components, we
      found that both saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA
      extract significantly suppressed pro-inflammatory cytokine and MMP-9 levels.
      Phytol and lutein, identified in the NS fraction, also inhibited cytokine
      production. Moreover, S and NS fractions of EA extract, phytol and lutein,
      activated peroxisome proliferator-activated receptor (PPAR) alpha and beta in the
      transactivation assay. Our results suggested that PPARalpha or PPARgamma
      signalling may contribute, at least in part, to the anti-inflammatory activity of
      WBM.

PMID- 22953814
TI  - Reductions in flesh discolouration and internal morphological changes in Nanhui
      peaches (Prunus persica (L.) Batsch, cv. Nanhui) by electrolysed water and 1
      methylcyclopropene treatment during refrigerated storage.
AB  - The effects of electrolysed water (EW) and EW in combination with 1
      methylcyclopropene (EW/MCP) on flesh discolouration of Nanhui peaches (Prunus
      persica (L.) Batsch, cv. Nanhui) were examined during storage at 2 degrees C.
      Changes in flesh colour, ethylene production, membrane permeability,
      malondialdehyde (MDA), total phenolic contents and the activities of polyphenol
      oxidase (PPO) and peroxidase (POD) were assayed periodically after harvest and
      during 44days of storage. The internal morphological characteristics of Nanhui
      peaches were monitored using magnetic resonance imaging (MRI) at the beginning
      and end of storage. These data revealed that the EW/MCP treatment is more
      effective than the EW treatment for decreasing ethylene production and
      maintaining fruit cell membrane integrity, delaying increases in MDA and total
      phenolic contents, and lessening changes in PPO and POD activities and the
      internal morphology of peaches. Each of these effects contributes to suppressing
      flesh discolouration and maintaining the quality of Nanhui peaches during
      storage.

PMID- 22953815
TI  - The functional property of egg yolk phosvitin as a melanogenesis inhibitor.
AB  - Phosvitin is a phosphoglycoprotein present in egg yolk. More than half of the
      amino acids in phosvitin molecule are serine, of which >90% are phosphorylated.
      Therefore, phosvitin has a strong metal binding capability. The aim of this study
      was to investigate the effect of phosvitin on the inhibition of melanogenesis in
      melanoma cells. The results showed that phosvitin inhibited the activity of
      mushroom tyrosinase. Addition of phosvitin at a concentration of 50MUg/ml, to
      B16F10 melanoma cells inhibited tyrosinase activity by approximately 42% and
      melanin synthesis by 17% compared to those in a control without phosvitin.
      Phosvitin inhibited the expression of tyrosinase, tyrosinase-related protein 1
      (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF) in
      B16F10 melanoma cells. In addition, phosvitin reduced the cellular cAMP
      concentration in B16F10 melanoma cells. These results indicate that phosvitin has
      the potential to be used as a melanogenesis inhibitor in the food and cosmetics
      industry.

PMID- 22953816
TI  - Cocoa polyphenols are absorbed in Caco-2 cell model of intestinal epithelium.
AB  - Cocoa is an abundant source of polyphenols, mainly flavan-3-ol monomers and
      polymers. In the literature, there are contradictory data on the absorption limit
      of procyanidins in humans. In our study, the Caco-2 cell model of intestinal
      epithelium was used to determine the absorption and secretion of cocoa flavan-3
      ols. Three compounds: (+)-catechin, (-)-epicatechin and procyanidin B2 were
      detected and quantified at the receiver side of Caco-2 monolayer after 2h
      transport experiment. The obtained results of apparent permeability coefficient
      suggest paracellular route of transport of investigated compounds. Additionally,
      the results suggest that compounds of cocoa powder purified extract are able to
      affect tight junction functioning.

PMID- 22953817
TI  - Assay of tyrosol and hydroxytyrosol in olive oil by tandem mass spectrometry and
      isotope dilution method.
AB  - Hydroxytyrosol and tyrosol, the strong antioxidant present in large amount in
      virgin olive oil have been assayed by LC-MS/MS under MRM condition and isotope
      dilution method, using d(2)-labelled internal standards obtained by simple
      synthetic procedures. The assay has been performed under MRM condition monitoring
      two transitions for each analyte to improve the specificity. This paper deals
      with a modern approach for assaying the content of this polyphenols in virgin
      olive oil down to a limit of a few hundreds of parts per billion. Tyrosol and
      hydroxytyrosol ranged from 10 to 47ppm and from 5 to 25ppm in commercial olive
      oil, respectively. The accuracy (98-107%) and analytical parameters values
      confirm the reliability of the proposed approach. The method can be extended to
      any natural matrices, including mill wastes, after a simple step of sample
      preparation.

PMID- 22953818
TI  - Synthesis and antioxidant activity of hydroxylated phenanthrenes as cis
      restricted resveratrol analogues.
AB  - Five hydroxylated phenanthrenes as "cis-configuration-fixed" resveratrol
      analogues differing in the number and position of the hydroxyl groups were
      designed and synthesized. Their antioxidant activity was studied by ferric
      reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl free radical
      scavenging, and DNA strand breakage-inhibiting assays, corresponding to their
      electron-donating, hydrogen-transfer and DNA-protecting abilities, respectively.
      In the above assays, their activity depends significantly on the number and
      position of the hydroxyl groups, and most of them are more effective than
      resveratrol. Noticeably, compound 9b (2,4,6-trihydroxyl phenanthrene) with the
      same hydroxyl group substitutions as resveratrol, is superior to the reference
      compound, highlighting the importance of extension of the conjugation over
      multiple aromatic-rings. Similar activity sequences were obtained in different
      experimental models, but the appreciable differences could contribute detailed
      insights into antioxidant mechanisms. Based on these results, the hydroxylated
      phenanthrenes may be considered as a novel type of resveratrol-directed
      antioxidants.

PMID- 22953819
TI  - Effects of cyclodextrins on the antimicrobial activity of plant-derived essential
      oil compounds.
AB  - Essential oils (EOs) from plants are considered to be a safer alternative when
      compared to synthetic antimicrobial food additives. However, a major drawback of
      many EOs is their hydrophobic nature, which makes them insoluble in water based
      media and matrices. Although cyclodextrins (CDs) can increase the solubility of
      EO compounds, the effects of CDs on the antimicrobial activity of EOs have not
      been reported. In this paper, four different EO compounds (carvacrol, eugenol,
      linalool and 2-pentanoylfuran) were chosen to study the influence of CDs on the
      solubility and antimicrobial activity on bacteria and yeast. The greatest
      enhancement with regards to solubility of the four test compounds was achieved by
      hydroxypropyl-beta-CD. In most instances, not only were the minimal antimicrobial
      concentrations of EO compounds decreased, but the interactivity of two combined
      EO compounds could be strengthened by the co-addition of CDs. Furthermore, the
      combination of carvacrol with hydroxypropyl-beta-CD caused a marked change in the
      major membrane lipid composition of all microorganisms investigated; while
      scanning electron microscopy revealed that cellular integrity was significantly
      affected by 2* MIC, ultimately resulting in cell lysis.

PMID- 22953820
TI  - Antioxidant activity, ascorbic acid, phenolic compounds and sugars of wild and
      commercial Tuberaria lignosa samples: effects of drying and oral preparation
      methods.
AB  - The antioxidant activity and phytochemical composition (ascorbic acid, free
      sugars and phenolic compounds) of decoctions and infusions of wild and commercial
      samples of Tuberaria lignosa (Sweet) Samp. Aerial parts were evaluated and
      compared. Among wild samples, the effects of the drying method (freeze or shade
      drying) on those parameters were studied. Infusion of the freeze-dried wild
      sample gave the highest levels of sugars, while infusion of shade-dried wild
      sample and decoction of the freeze-dried sample presented higher ascorbic acid
      and phenolic compounds content (including ellagitannins and flavonoids) than the
      other samples. The last two samples also revealed higher antioxidant activity, in
      some cases even higher than Trolox. Decoctions gave lower amounts of
      disaccharides than infusions, which seemed to be hydrolysed, increasing the
      content of monosaccharides. Commercial samples showed the lowest content in
      phenolic compounds, mainly in ellagitannins and flavonoids, and also the lowest
      antioxidant activity. This work gives scientific evidence to the traditional
      medicinal uses of wild Tuberaria lignosa, highlighting the interest of its
      decoctions and infusions as a source of bioactive compounds and functional
      beverages.

PMID- 22953821
TI  - Inhibition of beta-carotene degradation in oil-in-water nanoemulsions: influence
      of oil-soluble and water-soluble antioxidants.
AB  - The utilisation of carotenoids as functional ingredients (pigments and
      nutraceuticals) in many food and beverage products is currently limited because
      of their poor water-solubility, high melting point, chemical instability, and low
      bioavailability. This study examined the impact of antioxidants on the chemical
      degradation of beta-carotene encapsulated within nanoemulsions suitable for oral
      ingestion. beta-Carotene was incorporated into oil-in-water nanoemulsions
      stabilized by either a globular protein (beta-lactoglobulin) or a non-ionic
      surfactant (Tween 20). Nanoemulsions were then stored at neutral pH and their
      physical and chemical stability were monitored under accelerated stress storage
      conditions (55 degrees C). beta-Carotene degradation was monitored non
      destructively using colour reflectance measurements. The rate of beta-carotene
      degradation decreased upon addition of water-soluble (EDTA and ascorbic acid) or
      oil-soluble (vitamin E acetate or Coenzyme Q10) antioxidants. EDTA was more
      effective than ascorbic acid, and Coenzyme Q10 was more effective than vitamin E
      acetate. The utilisation of water-soluble and oil-soluble antioxidants in
      combination (EDTA and vitamin E acetate) was less effective than using them
      individually. Emulsions stabilized by beta-lactoglobulin were more stable to
      colour fading than those stabilized by Tween 20. These results provide useful
      information for designing effective nanoemulsion-based delivery systems that
      retard the chemical degradation of encapsulated carotenoids during long term
      storage.

PMID- 22953822
TI  - Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic
      extract of grape pomace from wine industrial waste.
AB  - The aim of the present study was to evaluate the vascular effects of an enzymatic
      extract of grape pomace (GP-EE) on isolated arteries, focusing our attention on
      endothelium-derived relaxation and on its antioxidant properties. Grape pomace
      derived from wine making was extracted by an enzymatic process and its
      composition of polyphenols was evaluated by HPLC and ESI-MS/MS, detecting
      kaempferol, catechin, quercetin and procyanidins B1 and B2, trace levels of
      resveratrol and tracing out gallocatechin and anthocyanidins. GP-EE induced
      endothelium- and NO-dependent vasodilatation of both rat aorta and small
      mesenteric artery (SMA) segments and reduced Phe-induced response in aortic
      rings. Both ORAC and DPPH assays confirmed antioxidant scavenging properties of
      GP-EE, which also prevented O(2)(.-) production (assessed by DHE fluorescence)
      and contraction elicited by ET-1. These results provide evidence that GP-EE
      possesses interesting antioxidant and protective vascular properties and
      highlight the potential interest of this extract as a functional food.

PMID- 22953823
TI  - Behaviour of polydiacetylene vesicles under different conditions of temperature,
      pH and chemical components of milk.
AB  - Blue polydiacetylene vesicles were studied with regard to their behaviour under
      variations in storage temperature, heating, potentiometric titration and in the
      presence of chemical components of milk, to evaluate their application as a
      sensor in the food industry. Vesicles were prepared using 10,12-pentacosadienoic
      acid (PCDA)/1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC). Their
      changes were monitored using UV-Vis absorption. Temperatures not exceeding 25
      degrees C did not cause colour change in PCDA/DMPC vesicles for a period of up to
      60days of storage. Heating for 10min at 60 and 90 degrees C, exposure to pH
      higher than 9.0 and the simulant solutions of the whey proteins, beta
      lactoglobulin and alpha-lactalbumin, promoted colour change from blue to red for
      the vesicles studied. The effects of routine factors on the characteristics and
      stability of polydiacetylene vesicles is important in defining the parameters
      related to their application as a sensor for the food industry.

PMID- 22953824
TI  - Chemical composition and starch digestibility in flours from Polish processed
      legume seeds.
AB  - The study was undertaken to determine the effect of various treatments, i.e.
      cooking after soaking, freezing after cooking and storage at a low temperature (
      18 degrees C, 21days), and autoclaving, of Polish cultivars of bean, pea and
      lentil seeds on the chemical composition and starch digestibility of the
      resultant flours. The cooking of seeds caused a significant decrease in contents
      of ash (by 11-48%), polyphenols (by 10-70%) and protein (to 19%) in flours made
      of bean. In addition, analyses demonstrated significantly decreased contents of
      resistant starch, RS (by 61-71%) and slowly digestible starch, SDS (by 56-84%).
      Storage of frozen seeds resulted in insignificant changes in the chemical
      composition, and in increased contents of both RS and SDS. The flours produced
      upon the autoclaving process were characterized by similar changes in the
      contents of ash and protein as in cooked seeds, yet losses of polyphenols were
      lower and, simultaneously, contents of RS and SDS were higher. All the analyzed
      flours were shown to be characterized by a reduced content of amylose in starch,
      which might have affected its digestibility. This was indicated by a strict
      negative correlation reported between the value of the starch digestion index
      (SDRI) and amylose content of starch (r=0.84, p>0.05).

PMID- 22953825
TI  - Effect of salinity stress on phenolic compounds and carotenoids in buckwheat
      (Fagopyrum esculentum M.) sprout.
AB  - The effect of salinity stress on the nutritional quality of buckwheat sprouts
      cultivated for 1, 3, 5, and 7d was investigated by analysis of the antioxidant
      activity and levels of phenolic compounds and carotenoids. Treatment with various
      concentrations of NaCl (10, 50, 100, and 200mM) resulted in an increase in the
      amount of phenolic compounds and carotenoids in the sprouts compared with the
      control (0mM). The phenolic contents of sprouts treated with 10, 50, and 100mM
      after 7d of cultivation were 57%, 121%, and 153%, respectively, higher than that
      of the control (0mM NaCl). Moreover, the accumulation of phenolic compounds was
      primarily caused by an increase in the levels of 4 compounds: isoorientin,
      orientin, rutin, and vitexin. The carotenoid content of sprouts treated with 50
      and 100mM NaCl was twice higher than that of the control. In addition, the
      antioxidant activity of ethanol extracts of the sprouts was increased by NaCl
      treatment. Although the growth rate of sprouts decreased with >50mM NaCl, these
      results suggest that treatment of an appropriate concentration of NaCl improves
      the nutritional quality of sprouts, including the level of phenolic compounds,
      carotenoids, and antioxidant activity.

PMID- 22953826
TI  - Monitoring pesticide residues in greenhouse tomato by combining acetonitrile
      based extraction with dispersive liquid-liquid microextraction followed by gas
      chromatography-mass spectrometry.
AB  - A multiclass and multiresidue method for pesticide analysis in tomato was
      validated. Extraction and pre-concentration of the pesticide residues from
      acetonitrile extracts was performed by using dispersive liquid-liquid
      microextraction (DLLME) technique, followed by gas chromatography-mass detection.
      DLLME was performed using carbon tetrachloride as extractive solvent and
      acetonitrile extract as dispersive solvent, in order to increase enrichment
      factor of the extraction procedure. Validation parameters indicated the
      suitability of the method for routine analyses of thirty pesticides in a large
      number of samples. In general, pesticide recoveries ranged between 70% and 110%
      and repeatability ranged between 1% and 20%. The proposed method was applied to
      the monitoring of pesticides in tomatoes grown during winter in greenhouses.
      Among the compounds considered in this work, cyprodinil was found in tomato at
      concentrations of 0.33mg/kg, other pesticides like azoxystrobin, fenhexanid,
      tolyfluanid, lambda-cyhalothrin and trifloxystrobin were also detected, but, not
      quantified.

PMID- 22953827
TI  - Development and validation of the high performance liquid chromatography-ion
      exclusion method for detection of lactic acid in milk.
AB  - The present work reports the development and validation of an analytical method
      for lactic acid quantification in milk by ion exclusion-HPLC with UV detection.
      This method showed good precision (variation coefficient <7.0%) and good accuracy
      (97.6-99.6%). Calibration curves were linear (R(2)>0.996) at the tested range of
      5.0-25.0mmolL(-1); and the detection and quantification limits were 0.5 and
      1.0mmolL(-1), respectively. Analysis of lactic acid in fermented milk (FM) or
      NaOH neutralised fermented milk (FNM) was performed using samples obtained during
      9h of fermentation. An ANOVA analysis combined with the Tukey test was used to
      show that the method was insensitive to the differences between FM and FNM. The
      proposed method therefore proved to be a useful quality control tool in
      laboratories because it was able to determine milk acidity even in adulterated
      samples.

PMID- 22953828
TI  - The influence of flavonoids on the binding of pantoprazole to bovine serum
      albumin by spectroscopic methods: with the viewpoint of food/drug interference.
AB  - The interaction of pantoprazole to bovine serum albumin (BSA) has been
      investigated with and without four popular 5,7,3',4'-hydroxy-substituted
      flavonoids, quercetin, luteolin, taxifolin and (+)-catechin. The presence of
      flavonoids decreased binding constants of pantoprazole with BSA from 39.7% to
      93.8%, which depended on flavonoid structures. Analysis of infrared spectroscopy
      (IR) and circular dichroism (CD) showed the binding of pantoprazole to BSA caused
      apparent change in secondary structure of BSA. The calculated values of spatial
      distance indicated the existence of quercetin, luteolin and taxifolin may compete
      with pantoprazole binding to BSA, while the existence of (+)-catechin possibly
      formed ternary pantoprazole-BSA-(+)-catechin complex. However, all the
      fluorescence quenching was initiated by static quenching procedure irrespective
      of the absence or presence of flavonoids, while van der Waals force and hydrogen
      bonds played major roles for pantoprazole-BSA association. All above results may
      have relevant consequence in rationalising the interferences of common food to
      gastric ulcer treatments.

PMID- 22953829
TI  - Tyrosinase inhibitory components of immature calamondin peel.
AB  - There is broad range of applications in the use of tyrosinase inhibitors for
      suppressing unwanted hyperpigmentation in human skin and enzymic browning in
      fruits. In searching effective tyrosinase inhibitors from natural products, the
      components in unripe calamondin (Citrus mitis Blanco) peel were investigated by
      performing bioassay-directed fractionation and chromatographic separation coupled
      with tyrosinase inhibition assay. Herein it is reported for the first time that
      (1) there is a rich content of 3',5'-di-C-beta-glucopyranosylphloretin in unripe
      calamondin peel, 3.69+/-0.44g/100g dry basis, (2) this C-glycosylated flavonoid
      showed the strongest inhibitory activity against tyrosinase among the components
      in this fruit, with an IC(50) of 0.87mg/ml, and (3) that unripe calamondin peel
      is also a rich source of naringin and hesperidin, 1.25% and 0.73% by dry weight,
      respectively, which also expressed strong tyrosinase inhibitory property.

PMID- 22953830
TI  - Structure characterization of a novel neutral polysaccharide isolated from
      Ganoderma lucidum fruiting bodies.
AB  - Ganoderma lucidum (G. lucidum) is a mushroom which has been used for health
      promotion for a long time in China. In the present work a neutral hetero
      polysaccharide, named FYGL-1, was isolated from FYGL which was reported
      previously capable of antihyperglycemia in vivo for further detailed chemical
      structure investigation. The results of monosaccharide composition and GPC
      analysis indicated that FYGL-1 consisted of galactose, rhamnose and glucose in
      mole ratio of 1.00:1.15:3.22 with a molecular weight of 78kDa. The detailed
      structure of FYGL-1 was characterized by periodate oxidation, Smith degradation,
      methylation analysis, along with FT-IR, GC, GC-MS, 1D (1)H and (13)C NMR and 2D
      NMR (HSQC, COSY, NOESY and TOCSY). Based on the analysis of the results, the
      structure of the repeating unit of FYGL-1 was established as:

PMID- 22953831
TI  - Bioavailability of glycitein relatively to other soy isoflavones in healthy young
      Caucasian men.
AB  - Glycitein is a Selective Estradiol Receptor Modulator (SERM) from soy. The study
      reports plasma bioavailability and urine excretion of glycitein compared to other
      soy isoflavones after a unique intake of food supplement based on soy germ
      containing 55.24mg isoflavones. Eighteen plasma and urinary sampling profiles
      collected over 48h from healthy young Caucasian men were analysed using specific
      ELISAs. Eight profiles contained equol. Glycitein T(max), C(max), AUC(0->24h) and
      T(1/2) in plasma were calculated. Urine T(max), % of excretion at 24h and
      clearance were assessed. Glycitein is one of the best absorbed flavonoids. Plasma
      steady-state level can be achieved by several intakes a day. Glycitein
      bioavailability is similar to that of daidzein and its urinary excretion is
      significantly higher than that of genistein. Equol does not affect glycitein
      bioavailability. Knowing glycitein bioavailability in man is essential for the
      development of soy-germ-based food supplements for health applications.

PMID- 22953832
TI  - Influence of barley variety and malting process on lipid content of malt.
AB  - The lipid content of a beer affects its ability to form a stable head of foam and
      plays an important role in beer staling. The concentration and the quality of
      lipids in beer depend on their composition in the raw materials and on the
      brewing process and they may exert considerable influence on beer quality. This
      paper presents an investigation of the influence of barley variety and malting
      process on the lipid content of finished malt. Five barley samples, grown in
      Italy, representing 4 spring barley and 1 winter barley were used. The samples
      were micro-malted and analysed. The aim of this research was to verify the
      influence of different barley varieties on the lipid content of malt and also on
      the changes in fatty acid (FA) profile during the malting process. Lipid content
      and FA profile were evaluated. Principal component analysis (PCA) was used to
      establish relationships between the different samples. An evaluation of the
      correlation between lipid content of barleys and the quality of the resulting
      malts was also conducted. The data showed that the total lipid content during the
      malting process decreased significantly as barley was converted into malt.
      Different barley varieties present different FA contents and different FA
      patterns. The correlation between the lipid content of barley and the quality of
      the resulting malt confirmed the negative influence of lipids.

PMID- 22953833
TI  - Gelatin hydrolysate from blacktip shark skin prepared using papaya latex enzyme:
      Antioxidant activity and its potential in model systems.
AB  - Antioxidant activities of gelatin hydrolysates from blacktip shark skin prepared
      using papaya latex enzyme with different degrees of hydrolysis (DHs: 10%, 20%,
      30% and 40%) were evaluated. All antioxidant activity indices of hydrolysates
      increased with increasing DH (P<0.05). When gelatin hydrolysate with 40%DH was
      determined for its pH and thermal stability, ORAC and chelating activity remained
      constant or slightly increased in a wide pH range (1-9) and during heating (100
      degrees C) for 240min. It was also stable in simulated gastrointestinal tract
      model system. Moreover, gelatin hydrolysate at a level of 500 and 1000ppm could
      inhibit lipid oxidation in both beta-carotene linoleate and cooked comminuted
      pork model systems. Therefore, gelatin hydrolysate from blacktip shark skin
      (40%DH) can potentially be used as an alternative source of natural antioxidants.

PMID- 22953834
TI  - Optimization of espresso machine parameters through the analysis of coffee
      odorants by HS-SPME-GC/MS.
AB  - The aroma profile and the final quality of espresso coffee (EC) are influenced by
      such technical conditions as the EC machine extraction temperature and the
      pressure used. The effect of these two parameters on EC quality were studied in
      combination by headspace solid phase micro extraction-gas chromatography-mass
      spectrometry (SPME-GC-MS) and sensory profile. Moreover, 10 key odorants at the
      best EC machine settings were examined to compare the two coffee cultivars
      (Arabica and Robusta) and two EC machines [Aurelia Competizione (A) and Leva
      Arduino (B)]. The data obtained provides important information about espresso
      making technique, suggesting that the usual espresso machine temperature and
      pressure settings (i.e. 92 degrees C and 9bar) are very close to those needed to
      obtain the best quality espresso. This confirms the traditional wisdom of coffee
      making, which judges 25ml, the typical volume of a certified Italian EC, to be
      ideal for very strong aroma intensity.

PMID- 22953835
TI  - Utilisation of chitinous materials in pigment adsorption.
AB  - The effect of adding the cells of four lactobacilli to a squid pen powder (SPP)
      containing medium on prodigiosin (PG) production by Serratia marcescens TKU011 is
      examined. The best increase in PG productivity was shown by strain TKU012. Among
      the samples of strain TKU012 and the chitinous materials of cicada casting powder
      (CCP), shrimp shell powder (SSP), squid pen powder (SPP), alpha-chitin, and beta
      chitin, TKU012 cells displayed the best adsorption rate (84%) for PG, followed by
      CCP, SSP, SPP, alpha-chitin, and beta-chitin. As for the water-soluble food
      colourants, Allura Red AC (R40) and Tartrazne (Y4), SPP and SSP had better
      adsorptive powers than pure chitin preparations, strain TKU012, and CCP.
      Treatment with organic solvents, hot alkali, or proteases (papain, bromelain)
      diminished the adsorption rates of the biosorbents.

PMID- 22953836
TI  - Influence of sulphur-fumigation on the quality of white ginseng: a quantitative
      evaluation of major ginsenosides by high performance liquid chromatography.
AB  - White ginseng was reported to be sulphur-fumigated during post-harvest handling.
      In the present study, the influence of sulphur-fumigation on the quality of white
      ginseng and its decoction were quantitatively evaluated through simultaneous
      quantification of 14 major ginsenosides by a validated high performance liquid
      chromatography. Poroshell 120 EC-C18 (100mm*3.0mm, 2.7MUm) column was chosen for
      the separation of the major ginsenosides, which were eluted with gradient water
      and acetonitrile as mobile phase. The analytes were monitored by UV at 203nm. The
      method was validated in terms of linearity, sensitivity, precision, accuracy and
      stability. The sulphur-fumigated and non-fumigated white ginseng samples, as well
      as their respective decoctions, were comparatively analysed with the newly
      validated method. It was found that the contents of nine ginsenosides detected in
      raw materials decreased by about 3-85%, respectively, and the total content of
      the nine ginsenosides detected in raw materials, decreased by almost 54% after
      sulphur-fumigation. On the other hand, the contents of 10 ginsenosides detected
      in decoctions of sulphur-fumigated white ginseng were decreased by about 33-83%,
      respectively, and the total content of ginsenosides was decreased by up to 64%
      when compared with that of non-fumigated white ginseng. In addition, ginsenoside
      Rh(2) and Rg(5) could be detected in the decoctions of sulphur-fumigated white
      ginseng but not in that of non-fumigated white ginseng. It is suggested that
      sulphur-fumigation can significantly influence not only the contents of original
      ginsenosides, but also the decocting-induced chemical transformation of
      ginsenosides in white ginseng.

PMID- 22953837
TI  - Synthesis and utilisation of molecular imprinting polymer for clean-up of
      propachlor in food and environmental media.
AB  - The molecularly imprinted polymers (MIPs) are used as the base material of solid
      phase extraction (SPE) for the separation and concentration of the propachlor
      herbicide (Prop) in different environmental matrix. Accordingly, we prepared MIPs
      on the surface of modified silica gel using propachlor as a template, acrylamide
      (AA) as functional monomers, ethylene glycol dimethacrylate (EGDMA) as a cross
      linker and 2,2-azo-bis-isobutyronitrile (AIBN) as an initiator. The MIP structure
      was characterised using scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FT-IR). Synthesised MIPs had a specific ability to detect
      the template Prop. The high selectivity solid phase extraction cartridges of
      molecularly imprinted polymers (MISPE) containing MIP Prop particles were
      prepared. The optimised Prop-MISPE procedure was developed for enrichment or
      clean-up of propachlor residues in water, soil and rice samples. Concentrations
      of propachlor in the samples were analysed by high performance liquid
      chromatography. Overall, the newly developed technique provides an analytical
      platform to quantify the trace amount of propachlor residues in multi or complex
      environmental and food media.

PMID- 22953838
TI  - Degradation of white wine haze proteins by Aspergillopepsin I and II during juice
      flash pasteurization.
AB  - Bentonite is commonly used to remove grape proteins responsible for haze
      formation in white wines. Proteases potentially represent an alternative to
      bentonite, but so far none has shown satisfactory activity under winemaking
      conditions. A promising candidate is AGP, a mixture of Aspergillopepsins I and
      II.; a food grade, well characterized and inexpensive protease, active at wine pH
      and at high temperatures (60-80 degrees C). AGP was added to two clarified grape
      juices with and without heat treatments (75 degrees C, 1min) prior to
      fermentation. AGP showed some activity at fermentation temperatures (~20% total
      protein reduction compared to control wine) and excellent activity when combined
      with juice heating (~90% total protein reduction). The more heat stable grape
      proteins, i.e. those not contributing to wine hazing, were not affected by the
      treatments and therefore accounted for the remaining 10% of protein still in
      solution after the treatments. The main physicochemical parameters and sensorial
      characteristics of wines produced with AGP were not different from controls.

PMID- 22953839
TI  - Induction of electrophile-responsive element (EpRE)-mediated gene expression by
      tomato extracts in vitro.
AB  - The market for food products with additional health benefits is increasing
      rapidly and tools for identification of bio-functional characteristics of food
      items are essential. To facilitate the detection of beneficial effects of tomato
      on gene expression, methods to prepare tomato extracts suitable to test in the
      EpRE LUX assay and other cell-based reporter gene assays for health-related
      bioactivity mechanisms, were developed. An isoprenoid-containing chloroform
      extract of tomato fruit and most individual isoprenoids did not induce
      electrophile-responsive element (EpRE)-mediated gene expression. A semi-polar
      extract of tomato fruits, enzymatically hydrolysed to remove the glycosyl
      residues from the phenolic ingredients was able to induce EpRE-mediated
      luciferase expression at both mRNA and protein level, which might be partly due
      to the presence of quercetin, kaempferol, naringenin and naringenin chalcone. It
      was concluded that induction of EpRE-regulated genes, such as detoxifying phase
      II and antioxidant enzymes, may contribute to the beneficial health effects of
      tomato.

PMID- 22953840
TI  - Picea mariana bark: a new source of trans-resveratrol and other bioactive
      polyphenols.
AB  - The ethyl acetate soluble fraction obtained from the hot water extract of Picea
      mariana bark (BS-EAc(f)) has been demonstrated to have anti-inflammatory and
      antioxidant properties. Thus, in the current study, we isolated and characterised
      major compounds of this fraction by HPLC, NMR and MS analyses. On the whole, 28
      compounds were identified, among which were five neolignans, seven lignans, trans
      resveratrol, three phenolic acids and four flavonoids. To the best of our
      knowledge, 2,3-dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-(2S,3S)
      1,4-benzodioxin-6-propanol, threo and erythro 3-methoxy-8,4'-oxyneolignan
      3',4,7,9,9'-pentol, pallasiin, (+/-) epi-taxifolin, homovanillyl alcohol, orcinol
      and 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol are reported for the
      first time in the Picea genus. P. mariana dry bark contains at least 104MUgg(
      1)dw of trans-resveratrol and it could be therefore considered as a new
      accessible source of this molecule. This study provides novel information about
      the identity of major compounds present in BS-EAc(f), which is essential for the
      understanding of the anti-inflammatory and nutraceutical potential of this
      extract.

PMID- 22953841
TI  - Hydrolysis of surimi wastewater for production of transglutaminase by
      Enterobacter sp. C2361 and Providencia sp. C1112.
AB  - Surimi wastewater (SWW) is an industrial wastewater, released during the washing
      step of surimi preparation from minced fish, that causes environmental problem.
      In this study, SWW produced from ornate threadfin bream (Nemipterus hexodon) was
      hydrolysed and used to cultivate Enterobacter sp. C2361 and Providencia sp. C1112
      for the production of microbial transglutaminase (MTGase, EC 2.3.2.13). The SWW
      was repeatedly used to wash the fish mince that gained a final protein content of
      3.20% (w/v). The commercial protease, Delvolase was the most appropriate protease
      used to produce fish protein hydrolysate (FPH) from SWW. The FPH at 40% degree of
      hydrolysis was used instead of a peptone portion in the SPY medium (3.0% starch,
      2.0% peptone, 0.2% yeast extract, 0.2% MgSO(4), 0.2% K(2)HPO(4) and 0.2%
      KH(2)HPO(4), pH 7.0) to cultivate the tested strains at 37 degrees C, shaking
      speed at 150rpm. Providencia sp. C1112 produced higher MTGase activity (1.78+/
      0.05U/ml) than Streptoverticillium mobaraense (1.61+/-0.02U/ml) at 18h of
      cultivation in FPH medium. On the other hand, the Enterobacter sp. C2361 produced
      lower MTGase activity (1.18+/-0.03U/ml).

PMID- 22953842
TI  - Production and functional characterisation of antioxidative hydrolysates from
      corn protein via enzymatic hydrolysis and ultrafiltration.
AB  - Corn protein was hydrolysed by three microbial proteases and further separated by
      sequential ultra-filtration to 12 hydrolysate fractions which were investigated
      for free radical scavenging capacity and chelating activity. The oxygen radical
      absorbance capacity (ORAC) of the hydrolysates varied significantly between 65.6
      and 191.4MUmoles Trolox equivalents (TE)/g dried weight with a small peptide
      fraction (NP-F3) produced by neutral protease (NP) possessing the highest
      antioxidant activity. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH())
      scavenging activities of the hydrolysate fractions also varied significantly
      between 18.4 and 38.7MUmoles TE/g. Two fractions (AP-F2 and AP-F3) produced by
      alkaline protease (AP) showed the strongest activity. However, no significant
      difference was detected on the chelating activity of the fractions. NP-F3, AP-F2,
      and AP-F3 were incorporated into ground beef to determine their effects on lipid
      oxidation during 15-day storage period. NP-F3 was the only fraction that
      inhibited lipid oxidation at both 250 and 500MUg/g levels by as much as 52.9%.

PMID- 22953843
TI  - Voltammetric determination of caffeine in beverage samples on bare boron-doped
      diamond electrode.
AB  - A sensitive and selective electrochemical method for the caffeine determination
      using bare boron-doped diamond electrode was developed. It was found that
      caffeine provided highly reproducible and well-defined irreversible oxidation
      peak at very positive potential. The effects of supporting electrolyte, pH and
      scan rate on the voltammetric response of caffeine oxidation were studied to
      select the optimum experimental conditions. Linear response of peak current on
      the concentration in the range from 4*10(-7) to 2.5*10(-5)M, good repeatability
      (RSD of 2.1%) and detection limit of 1.5*10(-7)M without any chemical
      modifications and electrochemical surface pretreatment were evaluated. The effect
      of possible interferents appeared to be negligible which evidently proved very
      good selectivity. The proposed method was successfully applied for the caffeine
      determination in commercially available beverage samples, with results in a close
      statistical agreement to those declared by manufacturer and HPLC used as
      independent method.

PMID- 22953844
TI  - Fatty acid alkyl esters presence in olive oil vs. organoleptic assessment.
AB  - The scientific work on the authenticity and quality of olive oil is an ever
      growing area. Olive oil genuineness is not only valuable for the producers, but
      also for the consumers who expect an actual correspondence between the products
      they purchase and the information on the packaging labels. Sometimes oil's
      rejection by consumers is just a matter of taste, sometimes is a more objective
      question. Low quality olive oils with weak organoleptic defects are the targets
      of illegal blends that can be detected by determining the content of fatty acid
      alkyl esters (FAAEs). In this line we have established a relationship between the
      FAAEs concentration of olive oils and their sensory classification. Besides, a
      connection between the presence of large quantities of FAAEs and fermentative
      organoleptic defects has been proven.

PMID- 22953845
TI  - Children's hedonic response to berry products: Effect of chemical composition of
      berries and hTAS2R38 genotype on liking.
AB  - The hedonic response of 104 healthy children, recruited from day-care centres and
      schools, to 12 different berry products with varying content of added sugar was
      studied. The berries used as ingredients were blackcurrant (Ribes nigrum), sea
      buckthorn (Hippophae rhamnoides), bilberry (Vaccinium myrtillus), and lingonberry
      (Vaccinium vitis-idaea). Another aim of the study was to study the effects of the
      chemical composition of berries as well as children's hTAS2R38 taste receptor
      genotypes on liking. The most liked product was bilberry with yoghurt, followed
      by bilberry juice, dried bilberries, and lingonberry rye bread. The most disliked
      products were sea buckthorn juice, sea buckthorn berries with yoghurt, and
      oatmeal with blackcurrant powder and berry oil. High total organic acid
      concentration was strongly related with a poor average liking score of the
      berries/berry products. A total of four different alleles of hTAS2R38 gene were
      observed in the study. Of the genotyped children, 45% were bitter taste
      insensitive individuals of the genotype AVI/AVI, and 40% were of the genotype
      PAV/AVI. Children of the genotype PAV/AVI were reported using more vegetables,
      but not berries, than the AVI/AVI children. The results also show that the liking
      scores of the children of the AVI/AVI, PAV/AVI, and PAV/PAV genotypes differed
      from each other, and that the familiarity of a berry product is likely to be an
      important factor in liking.

PMID- 22953846
TI  - Nitric oxide fumigation stimulates flavonoid and phenolic accumulation and
      enhances antioxidant activity of mushroom.
AB  - The effects of nitric oxide (NO) on antioxidant activity and contents of
      phenolics and flavonoids in mushroom Russula griseocarnosa were investigated.
      Freshly harvested mushrooms were fumigated with 0, 10, 20 and 30MULL(-1) NO at 20
      degrees C for 2h and then taken to examine the antioxidant activities using
      assays of reducing power, chelating effect on ferrous ions, scavenging effect on
      hydroxyl free radicals, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging
      activity. The results showed that the antioxidant activities of the mushrooms
      fumigated with NO were significantly increased when compared to the controls.
      Moreover, NO fumigation significantly enhanced phenolic and flavonoid contents
      and stimulated the activities of phenylalanine ammonia-lyase and chalcone
      synthase. The results indicated that NO fumigation might have potential
      application for enhancing the bioactive compounds and improving antioxidant
      activities in the mushrooms. Furthermore, the data suggested that the NO-induced
      phenolic and flavonoid accumulation was due to the activation of the biosynthetic
      pathways in the mushrooms.

PMID- 22953847
TI  - Histamine stability in Rihaakuru at -80, 4 and 30 degrees C.
AB  - Rihaakuru is a shelf stable fish paste product formed from a fish soup prepared
      from tuna. Histamine contamination is a food safety issue with this product that
      is manufactured from tuna fish that has been temperature abused. Histamine
      concentrations decreased between 31% and 73% in Rihaakuru stored for 10months at
      either -80, 4 or 30 degrees C. This appears to be a property of the product as
      histamine solutions are reported to be stable, at least under frozen storage. The
      risk of histamine food poisoning due to Rihaakuru may reduce during the storage
      of the product.

PMID- 22953848
TI  - Comparative proteome analysis of seed storage and allergenic proteins among four
      narrow-leafed lupin cultivars.
AB  - Lupin is an emerging crop worldwide due to its wide range of health benefits. In
      this study, a comprehensive proteome analysis was conducted using mature seed of
      four narrow leafed lupin cultivars, Uniharvest, Yorrel, Tanjil and Coromup,
      through two-dimensional gel electrophoresis followed by mass spectrometric
      protein sequencing. Two-dimensional gels recognised about 400 protein spots among
      the cultivars in the 10-100kDa molecular weight and 5.0-8.5 PI ranges. The
      results revealed a considerable variation of protein expression patterns with a
      total of 24 proteins showed differential expression among the cultivars, among
      which 19 were identified as beta-conglutin, and 8 were identified as allergenic
      proteins. Most of the alpha, delta and gamma-conglutins were showing similar
      expression among the cultivars. Overall, the differentially expressed proteins
      especially the cultivar specific proteins would be valuable markers for cultivar
      identification and for screening parental lines of low allergenicity in breeding
      process.

PMID- 22953849
TI  - Hypohalous acid-mediated halogenation of resveratrol and its role in antioxidant
      and antimicrobial activities.
AB  - The reactions of resveratrol with proinflammatory oxidants including hypochlorous
      and hypobromous acids in phosphate-buffered saline/methanol solution were carried
      out and eight halogenated resveratrol derivatives differing in the number and
      position of halogen atoms, and the configuration of double bond were obtained.
      Halogenation of resveratrol took place only at the aromatic A ring, and
      interestingly, the halogenation increased antioxidant activity of this parent
      molecule in the 2,2'-azobis(2-amidinopropane) hydrochloride-induced RBC
      haemolysis model. Additionally, antimicrobial activity of the derivatives against
      Gram-positive bacteria, Gram-negative bacteria and fungi were tested, and toward
      Candida albicans, 2-chloro-resveratrol and 2-bromo-resveratrol were more active
      than the unmodified form and the reference compound fluconazole.

PMID- 22953850
TI  - ACE inhibitory peptides and antioxidant peptides derived from in vitro digestion
      hydrolysate of hen egg white lysozyme.
AB  - Lysozyme from hen egg white is a well-known antimicrobial protein with high ratio
      of hydrophobic and positively charged amino acid residues. In order to explore
      functional bioactivities of enzymatic hydrolysates of lysozyme, the protein was
      subjected to a simulated gastrointestinal digestion and the resulting hydrolysate
      (LPH2) showed a strong competitive angiotensin I-converting enzyme (ACE)
      inhibitory activity (IC(50)=12.6MUg/ml) and a remarkable antioxidant activity.
      The LPH2 was fractionated using a 3kDa cut-off membrane and the obtained permeate
      LPH2-3kDa was analysed by MALDI-TOF-TOF MS. Using this technology, 38 different
      peptides were identified and some of these peptides were well fit with structure
      requirements of ACE inhibitory peptides and/or antioxidant peptides. The findings
      from this study suggest that the protein containing high proportion of
      hydrophobic and positively charged residues have the potential to generate
      multifunctional peptides, and these peptides would be beneficial ingredient to be
      used in functional foods.

PMID- 22953851
TI  - Thymus lotocephalus wild plants and in vitro cultures produce different profiles
      of phenolic compounds with antioxidant activity.
AB  - We compared the phenolic metabolites and antioxidant activities of Thymus
      lotocephalus G. Lopez & R. Morales wild plants and in vitro cultures using
      different extraction solvents. HPLC-DAD analysis allowed the identification and
      quantification of phenolic (caffeic and rosmarinic) acids and flavones (luteolin
      and apigenin) in extracts from both sources. The in vitro cultures accumulated
      large amounts of rosmarinic acid. However, extracts from both sources were able
      to neutralise free radicals in different test systems (TEAC and ORAC assays), to
      form complexes with Fe(2+) and to protect mouse brains against Fe(2+)-induced
      lipid peroxidation. The solvent significantly influenced the phenolic content and
      antioxidant activity of the extracts, water/ethanol being the most efficient for
      the extraction of antioxidant phytochemicals. We conclude that in vitro cultures
      of T. lotocephalus represent a promising alternative for the production of
      valuable natural antioxidants and an efficient tool for the in vitro biosynthesis
      of rosmarinic acid, therefore avoiding the need to exploit populations of wild
      plants.

PMID- 22953852
TI  - Enzymatic-fluorometric quantification of cholesterol in bovine milk.
AB  - The present paper describes an enzymatic-fluorometric method for the
      determination of cholesterol in milk and other opaque matrices. The initial step
      of the method is to liberate chemically and physically bound cholesterol from the
      milk fat globule membrane by enzymatic action. The method is able to discriminate
      between esterified and free cholesterol in milk. The analysis is cost effective
      and is developed to work directly on whole, fresh milk thereby eliminating time
      consuming and tedious pre-treatment procedures of the sample. More than 1000 milk
      samples were analysed on the day of sampling. The total concentration of milk
      cholesterol ranged from 80 to 756MUM (n=1068; mean 351MUM). Milk cholesterol was
      significantly correlated to milk fat concentration as analysed by mid-infra red
      spectrometry (r=0.630; n=853) and by an enzymatic-fluorometric method
      (triacylglycerol) (r=0.611; n=842).

PMID- 22953853
TI  - Determination of quarantine period in African catfish (Clarias gariepinus) fed
      with pig (Sus sp.) offal to assure compliance with halal standards.
AB  - Pig (Sus sp.) and pig by-products are considered as najasa (impurities) in Islam
      and forbidden in Muslim consumer products. Animals fed on najasa are categorised
      as al-jallalah (contaminated animals) which are allowed to be consumed as long as
      they have been quarantined for a certain period of time. During this quarantine
      period the animals will have undergone a natural purification process or
      istihalah. African catfish (Clarias gariepinus) are commonly consumed in Malaysia
      and may be fed on najasa. This study was carried out to estimate the istihalah
      period for catfish after feeding with pig offal, based on the absence of pig DNA
      in catfish gut and to suggest the quarantine period in catfish fed with pig
      offal. The results indicated that the maximum istihalah period could reach 36h in
      the stomach, 6h in the midgut and less than 2h in the hindgut although in many
      cases shorter periods were observed. Based on these results it is estimated that
      the minimum quarantine period for catfish fed with pig offal is 1.5days.

PMID- 22953854
TI  - Impact of lipid oxidation-derived aldehydes and ascorbic acid on the antioxidant
      activity of model melanoidins.
AB  - As the heat-induced formation of antioxidants throughout the Maillard reaction is
      known, this study was undertaken to evaluate the impact of lipid oxidation
      derived aldehydes and ascorbic acid in Maillard model systems on the resulting
      antioxidant activity. For this purpose, various fractions of melanoidin-like
      polycondensation products were obtained from mixtures of amino acids (glycine,
      lysine, arginine) and lipid oxidation-derived aldehydes (hexanal, (E)-2-hexenal),
      in the presence or absence of glucose or ascorbic acid. All fractions showed a
      significant radical scavenging capacity (DPPH assay) and ferric reducing power
      (FRAP assay). The activity varied according to the composition of the model
      system tested, although some similar trends were discovered in both assays
      applied. The presence of lipid oxidation products in the browning products
      augmented the antioxidant activity in specific cases. For instance, the combined
      presence of arginine, hexanal and glucose in heated model systems resulted in a
      significantly higher antioxidant capacity. With an exception of ascorbic acid
      containing model systems, melanoidin-like polycondensation products possessed
      significantly stronger antioxidant activities than the corresponding unheated
      initial reactant mixtures. Water-soluble high molecular weight (>12kDa) and
      nonsoluble fractions comprised the major part of the antioxidants derived from
      amino acid/lipid oxidation product model systems, with or without glucose or
      ascorbic acid.

PMID- 22953855
TI  - Metabolomic profiling of beer reveals effect of temperature on non-volatile small
      molecules during short-term storage.
AB  - The effect of temperature on non-volatile compounds in beer has not been well
      characterised during storage. Here, a metabolomics approach was applied to
      characterise the effect of storage temperature on non-volatile metabolite
      variation after 16weeks of storage, using fresh beer as a control. The metabolite
      profile of room temperature stored (RT) and cold temperature stored (CT) beer
      differed significantly from fresh, with the most substantial variation observed
      between RT and fresh beer. Metabolites that changed during storage included
      prenylated flavonoids, purines, and peptides, and all showed reduced quantitative
      variation under the CT storage conditions. Corresponding sensory panel
      observations indicated significant beer oxidation after 12 and 16weeks of
      storage, with higher values reported for RT samples. These data support that
      temperature affected beer oxidation during short-term storage, and reveal 5
      methylthioadenosine (5-MTA) as a candidate non-volatile metabolite marker for
      beer oxidation and staling.

PMID- 22953856
TI  - Lycopene degradation, isomerization and in vitro bioaccessibility in high
      pressure homogenized tomato puree containing oil: effect of additional thermal
      and high pressure processing.
AB  - In the present study, the effect of equivalent thermal and high pressure
      processes at pasteurization and sterilization intensities on some health related
      properties of high pressure homogenized tomato puree containing oil were
      investigated. Total lycopene concentration, cis-lycopene content and in vitro
      lycopene bioaccessibility were examined as health related properties. Results
      showed that pasteurization hardly affected the health related properties of
      tomato puree. Only the formation of cis-lycopene during intense thermal
      pasteurization was observed. Sterilization processes on the other hand had a
      significant effect on the health related properties. A significant decrease in
      total lycopene concentration was found after the sterilization processes. Next to
      degradation, significant isomerization was also observed: all-trans-lycopene was
      mainly converted to 9-cis- and 13-cis-lycopene. High pressure sterilization
      limited the overall lycopene isomerization, when compared to the equivalent
      thermal sterilization processes. The formation of 5-cis-lycopene on the other
      hand seemed to be favoured by high pressure. The in vitro lycopene
      bioaccessibility of high pressure homogenized tomato puree containing oil was
      decreased during subsequent thermal or high pressure processing, whereby
      significant changes were observed for all the sterilization processes.

PMID- 22953857
TI  - Antioxidant capacity and angiotensin I converting enzyme inhibitory activity of a
      melon concentrate rich in superoxide dismutase.
AB  - Antioxidant capacity and angiotensin 1-converting enzyme (ACE) inhibitory
      activity of a melon concentrate rich in superoxide dismutase (SOD-MC) were
      investigated in vitro. The total antioxidant capacity (TAC) was measured by the
      Trolox equivalent antioxidant capacity assay (TEAC), the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical assay, and the ferric reducing antioxidant power
      assay (FRAP). The ability of the extract to scavenge three specific reactive
      oxygen species (superoxide radical anion (O(2)(-)), hydroxyl radical (HO()) and
      hydrogen peroxide (H(2)O(2))) was also investigated in order to better evaluate
      its antioxidant properties. Even if the measures of TAC were relatively low,
      results clearly established an antioxidant potential of SOD-MC that exhibited the
      highest radical-scavenging activity towards O(2)(-), with a IC(50) 12-fold lower
      than that of H(2)O(2) or HO(). This lets hypothesis that the antioxidant
      potential of SOD-MC could be mainly due to its high level of SOD. Moreover, for
      the first time, an ACE inhibitory activity of SOD-MC (IC(50)=2.4+/-0.1mg/mL) was
      demonstrated, showing that its use as a functional food ingredient with potential
      preventive benefits in the context of hypertension may have important public
      health implications and should be carefully considered.

PMID- 22953858
TI  - Colloidal astaxanthin: preparation, characterisation and bioavailability
      evaluation.
AB  - Astaxanthin colloidal particles were produced using solvent-diffusion technique
      in the presence of different food grade surface active compounds, namely,
      Polysorbate 20 (PS20), sodium caseinate (SC), gum Arabic (GA) and the optimum
      combination of them (OPT). Particle size and surface charge characteristics,
      rheological behaviour, chemical stability, colour, in vitro cellular uptake, in
      vitro antioxidant activity and residual solvent concentration of prepared
      colloidal particles were evaluated. The results indicated that in most cases the
      mixture of surface active compounds lead to production of colloidal particles
      with more desirable physicochemical and biological properties, as compared to
      using them individually. The optimum combination of PS20, SC and GA could produce
      the astaxanthin colloidal particles with small particle size, polydispersity
      index (PDI), conductivity and higher zeta potential, mobility, cellular uptake,
      colour intensity and in vitro antioxidant activity. In addition, all prepared
      astaxanthin colloidal particles had significantly (p<0.05) higher cellular uptake
      than pure astaxanthin powder.

PMID- 22953859
TI  - A LC-MS/MS method for the determination of BADGE-related and BFDGE-related
      compounds in canned fish food samples based on the formation of [M+NH(4)](+)
      aducts.
AB  - A new and simple liquid chromatography tandem mass-spectrometry method for the
      determination of different bisphenol A (BPA) derivatives such as bisphenol A
      diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE) and their reaction
      products with water and hydrochloric acid in different fish food products was
      developed. The extraction procedure and the chromatographic conditions were
      optimised for complex food matrices such as fish products. Food samples were
      homogenised and extracted with a 1:1 solution of acetonitrile-hexane, the solvent
      was eliminated in a N(2) stream and the extract was reconstituted with 0.5mL of a
      0.01M solution of ammonium formate. The sample solution obtained was directly
      measured by LC-MS/MS without any further purification under the developed
      conditions. The use of a mobile phase composed by ammonium formate-methanol in a
      binary gradient mode produced [M+NH(4)](+) aducts for the different BADGEs and
      BFDGEs. These aduct's fragmentations were employed for the LC-MS/MS
      quantification of BPA derivatives in canned fish samples. The results of the
      validation were appropriate: the method was linear for BADGE and its hydrolysed
      derivatives up to 1000MUgkg(-1), for the remaining compounds linearity achieved
      up to 100MUgkg(-1). Quantification limits were in the range 2-10MUgkg(-1). RSD
      (intra and inter-day) was 6-12% and the recovery was comprised between 89% and
      109%. Under the optimised conditions, the chromatographic separation was
      performed in 8min per sample. The method was applied to the determination of
      BADGE, BFDGE and their reaction products in different samples of canned fish from
      Spanish origin. Migration results obtained were in compliance with the EU
      regulations.

PMID- 22953860
TI  - Pyrolytic formation of polycyclic aromatic hydrocarbons from sesquiterpenes.
AB  - The products of the pyrolysis of four sesquiterpenes, beta-caryophyllene, alpha
      cedrene, longifolene and valencene, have been examined. Pyrolysis was carried out
      at 300, 400 and 500 degrees C, the products determined by GC-MS and then examined
      for similarities and differences using multivariate data analysis. Analysis
      showed that longifolene was most resistant and caryophyllene least resistant to
      pyrolysis with cedrene and valencene occupying intermediate positions. While the
      compounds were largely unchanged at 300 degrees C, polycyclic aromatic
      hydrocarbons (PAHs) were major components of the pyrolysates at 400 and 500
      degrees C. No less than nine of the 16 EPA priority pollutants were present in
      the pyrolysates at the higher temperatures.

PMID- 22953861
TI  - Sensitive detection of ochratoxin A in wine and cereals using fluorescence-based
      immunosensing.
AB  - Ochratoxin A (OTA) is a mycotoxin found in a wide range of food and feedstuffs.
      Intake of OTA-contaminated food causes health concern due to the harmful effects
      reported on humans and animals. Much effort is currently devoted to set up and
      optimise highly sensitive and accurate methods of OTA analysis. This work
      describes the comparison of fluorescence-based immunosensing strategies for the
      analysis of OTA. First, an indirect competitive fluoroimmunoassay was designed
      and optimised. The assay enabled the quantification of the toxin at the levels
      set by the European legislation. Then, a flow-immunoassay based on kinetic
      exclusion measurements was developed. It showed the theoretical lowest limit of
      detection enabled by the affinity of the anti-OTA antibody (IC(80)=12ngL(-1) in
      the assay solution). Wine and cereal samples were analysed using the optimised
      flow system. No significant matrix effects were observed after simple pre
      treatment of wine and OTA extraction from corn-flakes samples. This simple and
      highly sensitive automated biosensing-system allows OTA quantification in food
      and beverages. It is envisaged as a powerful tool for rapid and reliable toxin
      screening.

PMID- 22953862
TI  - Direct detection of 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ) in food
      samples without derivatisation step by a sensitive and specific monoclonal
      antibody based ELISA.
AB  - AMOZ (3-amino-5-methylmorpholino-2-oxazolidinone) is the metabolite of
      furaltadone (FTD) which has been banned as a veterinary drug. In this study,
      three AMOZ derivatives (CPAMOZ) were synthesised and monoclonal antibody against
      o-nitrobenzaldehyde derivatived AMOZ (NPAMOZ) was produced. The IC(50) value of
      the ELISA for NPAMOZ was 0.17ngml(-1). The cross reactivity values of the assay
      with NPAMOZ, CPAMOZ, AMOZ and FTA were 100%, 61.7%, 14.8% and 10.4%,
      respectively. As no NPAMOZ or CPAMOZ exist if no derivitizing reagent added and
      FTA is quite unstable, therefore, 14.8% of cross reactivity with AMOZ makes the
      ELISA capable of directly detecting AMOZ without derivatisation. AMOZ spiked food
      samples were analysed by ELISA. Recoveries of 72.6-121.2% and intra-assay
      coefficients of variation of 6.1-17.7% were obtained. The proposed ELISA which
      also confirmed by HPLC with a good correlation provides an alternative sensitive
      and fast quantitative method for directly detecting AMOZ in food samples.

PMID- 22953863
TI  - Quantification of furanic compounds in coated deep-fried products simulating
      normal preparation and consumption: optimisation of HS-SPME analytical conditions
      by response surface methodology.
AB  - The validation of a method for the simultaneous quantification of furanic
      compounds in coated deep-fried samples processed and handled as usually consumed
      is presented. The deep-fried food was grinded using a device that simulates the
      mastication, and immediately analysed by headspace solid phase microextraction
      coupled to gas chromatography-mass spectrometry. Parameters affecting the
      efficiency of HS-SPME procedure were selected by response surface methodology,
      using a 2(3) full-factorial central composite design. Optimal conditions were
      achieved using 2g of sample, 3g of NaCl and 40min of absorption time at 37
      degrees C. Consistency between predicted and experimented values was observed and
      quality parameters of the method were established. As a result, furan, 2
      furfural, furfuryl alcohol and 2-pentylfuran were, for the first time,
      simultaneously detected and quantified (5.59, 0.27, 10.48 and 1.77MUgg(-1)
      sample, respectively) in coated deep-fried fish, contributing to a better
      understanding of the amounts of these compounds in food.

PMID- 22953864
TI  - Isolation and identification of lutein esters, including their regioisomers, in
      tritordeum (*Tritordeum Ascherson et Graebner) grains: Evidence for a
      preferential xanthophyll acyltransferase activity.
AB  - Liquid chromatography in conjunction with UV-visible spectroscopy and atmospheric
      pressure chemical ionisation (APCI) mass spectrometry has been used for the
      structural assignment of the lutein esters, including the regioisomeric forms,
      naturally occurring in the endosperm of tritordeum (*Tritordeum Ascherson et
      Graebner), a novel cereal. The distinctive mass spectrometry fragmentation
      pattern of lutein, characterized by a favored loss of the moieties at the
      position 3' of the epsilon-end ring, allowed an unambiguous structural
      identification of four monoesters (lutein 3'-O-linoleate, lutein 3-O-linoleate,
      lutein 3'-O-palmitate, lutein 3-O-palmitate) and four diesters (lutein
      dilinoleate, lutein 3'-O-linoleate-3-O-palmitate, lutein 3'-O-palmitate-3-O
      linoleate, lutein dipalmitate). This is the first time that the regioisomers of
      carotenoid esters have been identified in a cereal. Evidences for a preferential
      xanthophyll acyltransferase activity regarding the position (3 or 3') and the
      acyl moiety are discussed. Further studies should be carried out in order to
      identify the acyltransferase enzymes and the acyl donor molecules involved in the
      xanthophyll esterification process.

PMID- 22953865
TI  - Isorhapontigenin: a novel bioactive stilbene from wine grapes.
AB  - Stilbenes are a family of bioactive compounds found in plants. However, only a
      few stilbenes are present in the human diet. Grape and wine are the main dietary
      source of stilbenes, resveratrol and piceid being the most common ones.
      Ultraviolet C light (UVC) postharvest treatment was used to obtain significantly
      increased stilbene concentration in grapes. A new, previously undescribed-in
      grapes stilbene was found after UVC treatment. The process followed to isolate
      and identify this unknown stilbene is described in the present work. This
      isolation involved several fractionation steps including counter current
      chromatography and semi-preparative HPLC due to its low concentration and the
      presence of structurally related compounds. The structure of the compound was
      unequivocally identified by NMR spectroscopy analyses including (1)H-NMR; COSY;
      ROESY; HSQC and HMBC. The compound was identified as isorhapontigenin (ISOR), a
      stilbene found in traditional Asian medicinal plants. To the best of our
      knowledge this is the first report of its occurrence in grapes.

PMID- 22953866
TI  - Nutritional quality of protein in the leaves of eleven Asphodeline species
      (Liliaceae) from Turkey.
AB  - The nutritional quality of the protein in the leaves of 11 Asphodeline
      (Liliaceae) species was investigated by the determination of the amino acid
      composition and calculation of several nutritional parameters. The average
      protein content was 4.7% and ranged from 2.5% in Asphodeline damascena ssp.
      rugosa to 8.2% in A. turcica. The most abundant essential amino acids were Thr
      (5.7%), Val (6.0%), Ile (4.7%), and Trp (2.1%). The amino acid composition of
      Asphodeline peshmeniana was well equilibrated according to Food and Agriculture
      Organisation standards, but Lys and sulphur amino acids were at limiting
      concentrations in all the other taxa. Determination of the protein efficiency
      ratio and biological value revealed that the protein in the leaves of Asphodeline
      species is of high nutritional quality. Hence, the Asphodeline leaves that are
      typically used in Turkey for the preparation of salads, represent a good source
      of protein with high levels of several essential amino acids and a good
      nutritional value. Analysis of the similarity based on the amino acid composition
      indicated the existence of different clusters that are consistent with the
      taxonomical classification, area of distribution, and morphological similarities
      of the Asphodeline species.

PMID- 22953867
TI  - A critical evaluation on the reliability of two aluminum chloride chelation
      methods for quantification of flavonoids.
AB  - Flavonols kaempferol, quercetin, myricetin and gossypetin, and flavones apigenin,
      acacetin, luteolin, orientin and tricin, are subjected to two AlCl(3)
      spectrophotometric methods used for determination of total flavonoid content. The
      method developed by Woisky and Salatino involves addition of AlCl(3) solution to
      the flavonoid solution and recording of optical density at 420nm. All flavonols
      except kaempferol have absorption maxima above 440nm and so readings at 420nm are
      erroneous. Among flavones, all except for luteolin and orientin, have absorption
      maxima below 400nm. Further, addition of CH(3)COOK and recording the absorbance
      at 415nm, as modified by Chang et al., works well for flavonols kaempferol,
      quercetin and myricetin, but not for gossypetin. The flavones luteolin and
      orientin absorbed above 400nm, whereas all others absorbed below 400nm.
      Examination of the results of both methods indicates they are inadequate, and
      should not to be considered as universal and standard methods for total flavonoid
      determination.

PMID- 22953868
TI  - The role of electron-transfer and H-atom donation on the superb antioxidant
      activity and free radical reaction of curcumin.
AB  - Antioxidant activity of curcumin has been thoroughly studied to declare the
      conflicting conclusions about the site of curcumin reactivity and the reaction
      mechanisms in ROS scavenging. Data confirmed that the antioxidant activity of
      curcumin's enol isomer (CurE) is not only higher than keto isomer (CurK) but also
      more than trolox. We found that two phenolic OH play a major role in the
      antioxidant activity for the both of CurE and CurK tautomers. Interestingly;each
      one of CurE and CurK isomer is capable to reduce at least two free radicals by
      two possible labile phenolic O-H sites of reaction. CurK isomer of curcumin
      reacts by H-atom transfer mechanism but CurE has tendency to react predominantly
      by electron transfer. Therefore;data proposed that in neutral condition such as
      inside the cells where;CurK and CurE tautomerism of curcumin equilibrium
      present;both of H-atom and electron transfer mechanisms engage in reducing free
      radicals.

PMID- 22953869
TI  - Temperature-dependent stability and DPPH scavenging activity of liposomal
      curcumin at pH 7.0.
AB  - This paper investigated the influences of temperature on the stability and 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of curcumin
      encapsulated in liposome at pH 7.0. Liposomal curcumin showed higher stability
      and DPPH scavenging activity than free curcumin at 25 degrees C. When temperature
      increased from 25 to 80 degrees C, liposomal curcumin degraded more pronouncedly
      above the phase transition temperature (T(m)=45.7 degrees C) of liposome than
      lower temperatures, suggesting a weaker curcumin protection from the liquid
      crystalline phase of phospholipid bilayer than that from the gel phase. Moreover,
      the presence of remarkable "jump" increases around T(m) in the values of observed
      pseudo-first-order rate constant and the percent of DPPH scavenging activity of
      liposomal curcumin indicated that the liquid crystalline phase of phospholipid
      bilayer is more beneficial for curcumin to reduce DPPH. This study reveals that
      changing the microstructure of encapsulation carrier may effectively control the
      properties of phytochemicals like curcumin.

PMID- 22953870
TI  - Effect of natural antioxidant combinations on lipid oxidation in cooked chicken
      meat during refrigerated storage.
AB  - The effect of combinations of sage, oregano and honey on lipid oxidation in
      cooked chicken meat during refrigeration at 4 degrees C for 96h was determined.
      Chicken samples (thigh and breast) were then separated into five groups: control;
      butylated hydroxytoluene; oregano+sage; oregano+sage+5%honey and
      oregano+sage+10%honey. Quantitative measurements of thiobarbituric acid reactive
      substances, conjugated dienes, hexanal, fatty acids, cholesterol and cholesterol
      oxides were used as indicators of lipid oxidation. Acceptability and preference
      were also evaluated. The effectiveness of the natural antioxidants for reducing
      the velocity of lipid oxidation in cooked chicken thigh and breast was
      demonstrated after 48 and 96h of refrigeration at 4 degrees C. The treatments
      that presented the lowest hexanal values after 96h of refrigeration were
      oregano+sage+5%honey and oregano+sage+10%honey. Only traces of free cholesterol
      oxides were found (25-OH, 7-k, 7alpha-OH and 7beta-OH). The natural antioxidants
      protected cooked chicken meat from oxidation processes and resulted in great
      acceptability.

PMID- 22953871
TI  - Determination of biogenic amines in wine by thin-layer
      chromatography/densitometry.
AB  - Biogenic amines are small-molecular-weight organic bases that can be encountered
      in all fermented foods, including wine. Ingestion of wine containing biogenic
      amines, and especially histamine, can result in health nuisances. HPLC is the
      analytical technique most often employed in the determination of biogenic amines
      in wine but HPLC-based methods are expensive and time-consuming. A new method,
      based upon amine dansylation and TLC/densitometry, was developed and validated.
      This allowed for the determination of histamine, tyramine, putrescine and
      cadaverine in wine at concentrations between 1 and 20mg/L. Analytical
      performances adequately complied with the needs of routine wine analysis,
      moreover the method was high-throughput and inexpensive. A simpler, semi
      quantitative version of the method, based on visual evaluation of spot intensity,
      was also developed.

PMID- 22953872
TI  - Isolation and identification of phenolic compounds from the seeds of Perilla
      frutescens (L.) and their inhibitory activities against alpha-glucosidase and
      aldose reductase.
AB  - Five phenolic compounds were isolated from the seeds of Perilla (Perilla
      frutescens L.) using gradient solvent fractionation, silica gel column
      chromatography, and preparative high-performance liquid chromatography (HPLC).
      Their chemical structures were identified as caffeic acid-3-O-glucoside (1),
      rosmarinic acid-3-O-glucoside (2), rosmarinic acid (3), luteolin (4), and
      apigenin (5) using NMR spectroscopy and HPLC-ESI/MS analysis. Among them,
      luteolin (4) inhibited alpha-glucosidase (EC 3.2.1.20) with IC(50) value of
      45.4MUM. The inhibition kinetic analysed by Dixon plot indicate that luteolin is
      a noncompetitive inhibitor, and the inhibition constant K(I) was calculated at
      45.0MUM. Moreover, rosmarinic acid (3) and luteolin (4) inhibited recombinant
      human aldose reductase (EC 1.1.1.21) with IC(50) values of 11.2 and 0.6MUM,
      respectively. Notably, the inhibition kinetic of luteolin (4) follows a
      hyperbolic dependence on aldose reductase inhibition by Dixon plot. Thus,
      inhibition kinetic indicates that luteolin (4) is a mixed-type inhibitor.

PMID- 22953873
TI  - Effects of gelation temperature on Mozzarella-type curd made from buffalo and
      cows' milk: 2. Curd yield, overall quality and casein fractions.
AB  - The overall quality of Mozzarella-type curds made from buffalo and cows' milks
      were measured at gelation temperatures of 28, 34 and 39 degrees C, and cutting
      times of 45, 60, 75 and 90min after chymosin addition. The curd yield and
      moisture content decreased with increasing gelation temperature, while whey fat
      losses increased. The effect of higher gelation temperature (39 degrees C) was
      more pronounced in cows' milk than buffalo milk. This results in more fat losses
      and lower yields in both milk samples at a gelation temperature of 39 degrees C.
      The minimum losses of fat and protein in rennet whey occurred at a gelation
      temperature of 34 degrees C in both milk samples. The curd yield was higher in
      buffalo milk as compared to cows' milk. This is due to difference in total solids
      (fat and protein contents) of the two types of bovine milk. The different cutting
      times had a small effect on the yield and overall quality of curds made from both
      milk types. Curd moisture and loss tangent have a strong relationship with
      respect to effects of gelation temperature. Two different curd drainage methods
      (centrifugation and Buchner funnel filtration) were used to compare the final
      overall quality of Mozzarella-type curds made from both milk types. The alpha(s1)
      and beta casein fractions were found to be in different proportions in the two
      milk types. The total- and casein bound-calcium were higher in buffalo milk than
      cows' milk. The total protein, casein and fat were also found to be higher in
      buffalo milk than cows' milk.

PMID- 22953874
TI  - Probiotic viability and physico-chemical and sensory properties of plain and
      stirred fruit yogurts made from goat's milk.
AB  - Probiotic plain and stirred fruit yogurts were made from goat's milk using
      bacterial cultures comprising, Lactobacillus acidophilus LA-5, Bifidobacterium
      animalis subsp. lactis BB-12 and Propionibacterium jensenii 702. The products
      were stored at 4 degrees C for 4weeks, during which time the viability of the
      yogurt starter culture and probiotic bacteria was analysed weekly. P. jensenii
      702 demonstrated the highest viability (10(8)cfu/g) in all types of yogurt
      throughout the storage period, while the viability of the bifidobacteria
      (~10(7)cfu/g) also remained above the minimum therapeutic level. The viability of
      L. acidophilus LA-5 fell below 10(6)cfu/g in yogurts, however, the addition of
      fruit juice appeared to support the viability of lactobacilli, with higher
      microorganism numbers observed in fruit yogurts than in plain yogurt throughout
      the shelf life. Addition of fruit juice significantly increased the syneresis,
      and decreased viscosity and water holding capacity of yogurts (p<0.05), and also
      enhanced their sensory acceptability.

PMID- 22953875
TI  - Isolation of powerful antioxidants from the medicinal halophyte Limoniastrum
      guyonianum.
AB  - The antioxidant capacities of the crude extract, aqueous and ethyl acetate
      partitions of Limoniastrum guyonianum Boiss. (Zita) were investigated in this
      study. The ethyl acetate phase exhibited a significant antioxidant activity as
      judged by total antioxidant activity, DPPH test and reducing power. Fractionation
      of this extract by centrifugal partition chromatography (CPC) using quaternary
      Arizona solvent systems composed of n-heptane/ethyl acetate/methanol/water led to
      ten fractions. The antioxidant capacities of these fractions were assessed using
      the same previous tests. Fraction 8 showed the highest antioxidant capacity
      (1291.1mg GAE/g DR), the power ability to quench DPPH radical (IC(50)=2MUg/ml)
      and to reduce Fe(3+) (EC(50)=65MUg/ml). From this fraction, three powerful
      flavonoids were isolated (1-3): gallocatechin (1), epigallocatechin (2) and
      epigallocatechin-3-O-gallate (3). These findings suggest that the antioxidative
      property of L. guynianum is may be related to the presence of these flavonoids,
      which can be used in various industrial fields.

PMID- 22953876
TI  - Classification and characterisation of Spanish red wines according to their
      appellation of origin based on chromatographic profiles and chemometric data
      analysis.
AB  - Chromatographic profiles of wines have been used as a fingerprint for the
      discrimination of Spanish wines based on oenological practices. In order to
      extract information of different families of phenolic compounds, profiles of
      different UV-vis absorption wavelengths (280, 310, 370 and 520nm) and
      fluorescence (ex=260nm; em=360nm) were analysed. A total of thirteen phenolic
      compounds which allowed the discrimination of wines of three different Spanish
      appellations (Penedes, Rioja and Ribera del Duero) were selected by means of
      principal component analysis (PCA). Afterwards, these compounds were used to
      build partial least squares discriminant analysis (PLS1-DA and PLS2-DA) models
      which allowed the discrimination of wines according to their appellation with
      classification rates for independent test sets higher than 96% and 93% for PLS1
      DA and PLS2-DA models respectively. Finally, characteristic compounds of each
      appellation were tentatively identified by means of liquid chromatography-mass
      spectrometry (LC-MS) analysis. Thus, ten out of thirteen compounds (i.e., gallic
      acid for Penedes, trans-coumaroyltartaric and trans-caffeoyltartaric acids for
      Rioja and myricetin for Ribera del Duero wines) have been proposed.

PMID- 22953877
TI  - Moisture absorption and retention properties, and activity in alleviating skin
      photodamage of collagen polypeptide from marine fish skin.
AB  - Collagen polypeptides were prepared from cod skin. Moisture absorption and
      retention properties of collagen polypeptides were determined at different
      relative humidities. In addition, the protective effects of collagen polypeptide
      against UV-induced damage to mouse skin were evaluated. Collagen polypeptides had
      good moisture absorption and retention properties and could alleviate the damage
      induced by UV radiation. The action mechanisms of collagen polypeptide mainly
      involved enhancing immunity, reducing the loss of moisture and lipid, promoting
      anti-oxidative properties, inhibiting the increase of glycosaminoglycans,
      repairing the endogenous collagen and elastin protein fibres, and maintaining the
      ratio of type III to type I collagen.

PMID- 22953878
TI  - Nanoemulsion delivery systems: influence of carrier oil on beta-carotene
      bioaccessibility.
AB  - Consumption of carotenoids may reduce the incidences of certain chronic diseases,
      but their use in foods is currently limited because of their poor water
      solubility, low bioavailability and chemical instability. We examined the impact
      of carrier oil type on the bioaccessibility of beta-carotene encapsulated within
      nanoemulsion-based delivery systems. Oil-in-water nanoemulsions (d<200nm) were
      formed using a non-ionic surfactant (Tween 20) as emulsifier and long chain
      triglycerides (LCT), medium chain triglycerides (MCT) or orange oil as carrier
      oils. The influence of carrier oil type on beta-carotene bioaccessibility was
      established using an in vitro model to simulate the oral, gastric and small
      intestinal phases of the gastrointestinal tract. The rate and extent of free
      fatty acid production in the intestine decreased in the order LCT~MCT?orange oil;
      whereas beta-carotene bioaccessibility decreased in the order LCT?MCT>orange oil.
      The bioaccessibility of beta-carotene was negligible (~0%) in orange oil
      nanoemulsions because no mixed micelles were formed to solubilise beta-carotene,
      and was relatively low (~2%) in MCT nanoemulsions because the mixed micelles
      formed were too small to solubilise beta-carotene. In contrast, beta-carotene
      bioaccessibility was relatively high (~66%) in LCT nanoemulsions. Our results
      have important implications for the design of effective delivery systems for
      encapsulation of carotenoids and other lipophilic bioactive components.

PMID- 22953879
TI  - Effect of high hydrostatic pressure on antimicrobial activity and quality of
      Manuka honey.
AB  - The antimicrobial activity of Manuka honey is of major interest to beekeepers and
      the honey industry. In this study, the effect of high hydrostatic pressure and
      thermal treatments on antimicrobial activity and quality parameters (principally,
      diastase number and hydroxymethylfurfural levels (HMF)) of Manuka honey were
      investigated. The honey was subjected to different pressures (100-800MPa) at 25
      degrees C for a range of holding times (15-120min). The antimicrobial activity
      was found to increase with applied pressure for a given holding time, while the
      diastase number and HMF levels remained, more or less, unaffected. The percentage
      inhibition in microbial growth correlated linearly (R(2)=0.94) with methyglyoxal
      concentration in the honey after treatment over the entire range of pressure,
      temperature and holding times studied. Maximum percentage inhibition (78.83%) was
      achieved when honey was subjected to 800MPa compared to the control (57.93%).
      Thermal treatments at higher temperatures were found to have a detrimental effect
      on antimicrobial activity based on percentage inhibition as well as methylglyoxal
      content. Thus, it can be concluded that the levels of methylglyoxal, and
      therefore the antimicrobial effect of Manuka honey, can be enhanced by using high
      pressure processing without adversely affecting honey quality.

PMID- 22953880
TI  - Analysis on the effectiveness of co-solute on the network integrity of high
      methoxy pectin.
AB  - Co-solute requirements for high methoxy pectin gelation were observed by the
      addition of glucose syrup and polydextrose at concentrations varying from 50% to
      78% (w/w). Pectin content was fixed at 2% (w/w) in formulations. Studies from
      small deformation dynamic oscillation in shear, modulated differential scanning
      calorimetry and environmental scanning electron microscopy are reported.
      Structural properties of pectin preparations were recorded in relation to the
      molecular weight and concentration of added co-solute in an acidic environment
      (pH ~3.0). High levels of co-solute induce formation of weak pectin gels at
      elevated temperatures (even at 95 degrees C), which upon subsequent cooling
      exhibit increasing strength and convert to a clear glass at subzero temperatures.
      Fourier Transform Infrared Spectroscopy and wide angle X-ray diffraction were
      practised to examine the nature of interactions between polymer and co-solute and
      the extent of amorphicity of preparations. Glucose syrup is an efficient
      plasticiser leading to a reduction in the glass transition temperature (T(g)) of
      the pectin network, whereas polydextrose assists in the formation of stronger
      pectin gels in the rubbery state.

PMID- 22953881
TI  - Isolation and identification of flavour peptides from Puffer fish (Takifugu
      obscurus) muscle using an electronic tongue and MALDI-TOF/TOF MS/MS.
AB  - To clarify the key flavour peptides that account for the cooked taste of puffer
      fish, this study was performed to examine flavour peptides extracted from the
      flesh of puffer fish (Takifugu obscurus). Peptides fractions (P1, P2, P3, P4 and
      P5) were purified from an aqueous extract of T. obscurus muscle by
      ultrafiltration and Sephadex G-15 gel filtration chromatography (GFC). P2 was
      further fractionated into P2a, P2b, and P2c by reverse phase high performance
      liquid chromatography (RP-HPLC). Fraction P2b elicited umami and sweet taste. The
      amino acid sequence of P2b subfraction was identified as Tyr-Gly-Gly-Thr-Pro-Pro
      Phe-Val (836.4Da) by matrix-assisted laser desorption/ionisation time of flight
      mass spectrometry (MALDI-TOF/TOF MS/MS). Hydrophilic amino acids residues Tyr,
      Gly, Gly, Thr, and Phe are likely to contribute to the umami and sweet taste of
      this octapeptide. The results of this study suggest this peptide is one of
      important components of the 'mellowness' and 'tenderness' taste of the T.
      obscurus.

PMID- 22953882
TI  - Purification of naringin and neohesperidin from Huyou (Citrus changshanensis)
      fruit and their effects on glucose consumption in human HepG2 cells.
AB  - Huyou (Citrus changshanensis) is rich in naringin and neohesperidin, which are
      natural flavanone glycosides with a range of biological activities. Among the
      different fruit parts, i.e. flavedo, albedo, segment membrane (SM), and juice
      sacs (JS), albedo showed the highest contents of both compounds, with 27.00 and
      19.09mg/g DW for naringin and neohesperidin, respectively. Efficient simultaneous
      purification of naringin and neohesperidin from Huyou albedo was established by
      the combination of macroporous D101 resin chromatography and high-speed counter
      current chromatography (HSCCC). Purified naringin and neohesperidin were
      identified by both HPLC and LC-MS, and their effects on glucose consumption were
      investigated in HepG2 cells. Cells treated with naringin and neohesperidin showed
      increased consumption of glucose, and this was associated with increased
      phosphorylation of AMP-activated protein kinase (AMPK). Therefore, naringin and
      neohesperidin from Huyou may act as potential hypoglycaemic agents through
      regulation of glucose metabolism.

PMID- 22953883
TI  - Functional properties and in vitro antioxidant activity of roe protein
      hydrolysates of Channa striatus and Labeo rohita.
AB  - Bioactive roe protein hydrolysates were prepared from Channa striatus (CRPH) and
      Labeo rohita (LRPH) and their functional and in vitro antioxidant properties
      evaluated. The degree of hydrolysis was 28.41% at 60min in channa and 18.85% in
      labeo roe concentrates at 90min. The yields of protein hydrolysates were 24.15%
      and 12.45% for channa and labeo roe protein concentrates, respectively. The
      protein content was identical (58%) in both roe protein hydrolysates. Protein
      solubility in channa was higher (90.48%) when compared to labeo (50.6%) at pH 12.
      Higher oil absorption capacity and foam stability were observed in CRPH and
      higher emulsifying capacity was found in LRPH. Smaller peptides of 12kDa were
      noted in both CRPH and LRPH. In vitro antioxidant activity was higher in CRPH
      than in LRPH as seen from DPPH radical scavenging and ferric reducing power.

PMID- 22953884
TI  - Deconvolution of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry isotope patterns to determine ratios of A-type to B-type interflavan
      bonds in cranberry proanthocyanidins.
AB  - A method to deconvolute overlapping isotope patterns in positive mode matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) was developed to determine ratios of A- to B-type interflavan bonds in
      proanthocyanidins that were isolated from cranberry (Vaccinium macrocarpon, Ait.)
      press cake (c-PAC). Precision and accuracy was validated for binary mixtures of
      procyanidins A2 and B2. Deconvolution of c-PAC spectra indicated that oligomers
      with one or more A-type interflavan bonds occur in a higher proportion than
      oligomers with all B-type interflavan bonds. c-PAC with at least one A-type bond
      accounted for more than 91% of the oligomers between trimers and undecamers. The
      c-PAC isotope patterns are highly repeatable, suggesting that the method can be
      applied to authentication, standardization and efficacy of cranberry products in
      relationship to urinary tract health. This is the first time MALDI-TOF MS has
      been used for estimating ratios of A- to B-type bonds in PAC.

PMID- 22953885
TI  - Effect of the production method on the properties of RS3/RS4 type resistant
      starch. Part 1: properties of retrograded starch (RS3) produced under various
      conditions and its susceptibility to acetylation.
AB  - The objective of this study was to establish the effect of the concentration of a
      starch paste subjected to freezing on the properties of the produced retrograded
      starch, and to determine its susceptibility to acetylation with acetic acid
      anhydride. A starch paste (1, 4, 10, 18 or 30g/100g) was produced from native
      potato starch that was frozen, defrosted and dried. Al preparations of
      retrograded starch had the same chemical structure determined with the technique
      of nuclear magnetic resonance (NMR) and diversified physical form visible on
      photos taken with an electron microscope (SEM). An increase in the concentration
      of paste, used to produce the preparations, resulted in decreased: amylose
      content (from 25.0 to 20.4/100g), solubility in water (from 41.1 to 20.1/100g),
      swelling power (from 45.0 to 19.3/g), and susceptibility of the preparations to
      the action of amyloglucosidase (from 95.4 to 83.6/100g). The heat of phase
      transition of solubilisation determined with differential scanning calorimetry
      (DSC) ranged from 3.8 to 7.1J/g, and the initial temperature of transition was
      increasing from 43.4 to 49.7 degrees C along with an increasing concentration of
      the paste subjected to retrogradation. The 1-10/100g concentration of the paste
      used to produce preparations was observed to increase, whereas that between 10
      and 30/100g to decrease the susceptibility to acetylation and viscosity of the
      prepared pastes, determined both with a Brabender viscograph and a Haake
      oscillating-rotational viscosimeter.

PMID- 22953886
TI  - Lavandula luisieri essential oil as a source of antifungal drugs.
AB  - This work reports the antifungal activity of Lavandula luisieri essential oils
      against yeast, dermatophyte and Aspergillus strains responsible for human
      infections and food contamination. The oil's cytotoxicity and its effect on the
      yeast-mycelium transition in Candida albicans, an important virulence factor,
      were also evaluated. Analyses by GC and GC/MS showed a peculiar composition of
      irregular monoterpenes. Significant differences between the samples occurred in
      the amounts of 1,8-cineole, fenchone and trans-alpha-necrodyl acetate. The oil
      with higher amounts of irregular monoterpenes was the most effective. The
      influence of the oils on the dimorphic transition in C. albicans was also studied
      through the germ tube inhibition assay. Filamentation was completely inhibited at
      concentrations sixteen times lower than the minimal inhibitory concentration. The
      results support the use of L. luiseiri essential oils in the development of new
      phytopharmaceuticals and food preservatives and emphasise its antifungal
      properties at concentrations not cytotoxic or with very low detrimental effects
      on mammalian cells.

PMID- 22953887
TI  - Free amino acids and biogenic amines in Alicante Monastrell wines.
AB  - The simultaneous determination of 17 free amino acids and 8 biogenic amines in
      Alicante Monastrell wines was investigated for the first time. The quantification
      was carried out by using a RP-HPLC method, based on a pre-column derivatization
      with o-phthaldialdehyde (OPA) and fluorescence detection. From the results
      obtained it may be concluded that the most abundant free amino acids were Glu,
      Arg, Ala Asp, and Lys. None of the wine samples analysed had histamine (HIM) or
      Tyramine (TYM) levels above the limits considered as a possible toxic risk for
      healthy individuals. No measurable amounts of cadaverine (CAD) or methylamine
      (MEA) were found, showing no spoilage symptoms of sensory properties of the
      wines. Tryptamine (TRM) content was significantly higher in aged wines compared
      to young wines. However ethanolamine (ETA) content was lower. These data were
      used to make a preliminary classification of the samples using cluster analysis.

PMID- 22953888
TI  - Chemical, technological and in vitro antioxidant properties of mango, guava,
      pineapple and passion fruit dietary fibre concentrate.
AB  - The aim of this work was to determine the chemical, technological and in vitro
      antioxidant properties of co-products from the industrialisation of some tropical
      exotic fruits, such as mango, pineapple, guava and passion fruit, and to evaluate
      their potential use as dietary fibre sources for food enrichment. Proximate
      compositions were determined, as well as the total, insoluble and soluble fibre
      contents. The water holding, oil holding and swelling capacities were also
      determined. For the antioxidant activity, three different test systems were used
      (ABTS, DPPH and FRAP). The dietary fibre content of the co-products varied in a
      range between 69.1 and 81.5g/100g on a dry matter basis with a good balanced
      ratio between insoluble dietary fibre and soluble dietary fibre. Phenol recovery
      was dependent on the fruit type and the solvent system used. Methanol:acetone was
      a more efficient solvent for extracting phenols than ethanol. There was a good
      correlation between total phenol content and antioxidant capacity of the fruit
      extracts. All samples analysed had good antioxidant capacity. The results of this
      study indicate that exotic fruit fibres obtained as co-products in the process to
      obtain juice may be considered a good source of natural compounds with
      significant antioxidant activity.

PMID- 22953889
TI  - Effect of pre-dehydration treatment on the in vitro digestibility of starch in
      cookie.
AB  - In order to understand the effect of pre-dehydration on the in vitro
      digestibility of cookie starch, cookie dough samples were dehydrated by vacuum
      treatment, and melting temperature (T(m)) of the crystalline amylopectin in the
      dough, internal temperature and water content of the dough during baking, and non
      hydrolysed starch content of the obtained cookies were investigated. The T(m) of
      crystalline amylopectin increased with decreased water content of the dough, and
      the result was described as a T(m)-curve. The internal temperature of non
      dehydrated dough surpassed the T(m)-curve during baking. Pre-dehydrated dough, on
      the other hand, always indicated a lower internal temperature than the T(m)
      curve. The non-hydrolysed starch content obtained under a given condition
      increased significantly with a decrease in the initial water content of cookies.
      This will be because the melting of crystalline amylopectin was prevented, at
      least partially, during baking.

PMID- 22953890
TI  - Can artisanal "Coalho" cheese from Northeastern Brazil be used as a functional
      food?
AB  - Brazilian artisanal "Coalho" cheeses from six Northeast towns were investigated
      as a functional food based on their peptide profiles and antioxidant, zinc
      binding and antimicrobial activities. The peptides (WSP) from "Coalho" cheese
      showed high antioxidant activity, the best value of TEAC being 2223+/-10.10MUM,
      which means 91.1+/-0.43% oxidative inhibition and peptide concentration for
      IC(50) of 7mg/mL (21MUg of peptides) for sample from the town of Correntes. The
      smallest TEAC value (1896+/-17MUM), which means 75.9+/-0.7% oxidative inhibition
      and IC(50) of 10.5mg/mL (31.5MUg of peptide), was obtained for samples from the
      town of Sao Bento do Una. The zinc-binding activities were: Arcoverde (72.21+/
      0.24%) Cachoeirinha (75.02+/-0.02%), Capoeiras (61.78+/-0.65%), Correntes
      (75.47+/-0.5%), Sao Bento do Una (75.41+/-0.15%), and Venturosa (74.36+/-0.04%).
      The WSP extracts showed antimicrobial activity against Enterococcus faecalis,
      Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. All the results
      obtained suggest that "Coalho" cheese has potential as a functional food.

PMID- 22953891
TI  - Antioxidant properties and essential oil composition of Calamintha grandiflora L.
AB  - Essential oil was isolated from the leaves of Calamintha grandiflora L. by
      hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS).
      The most abundant compounds in C. grandiflora essential oil were isomenthone, neo
      isomenthol, pulegone and isomenthol, constituting 34.07%, 7.65%, 19.83% and
      19.54%, respectively. The residues obtained after hydrodistillation were
      separated into the solid and liquid fractions, the former one was extracted with
      acetone, methanol and ethanol, while the latter one was sprayed or freeze dried.
      Antioxidant potential of extracts was evaluated by DPPH() (batch and HPLC-on
      line) and ABTS(+) radical scavenging, ferric ion reduction (FRAP) assays and by
      the effect on oil peroxidation in Oxipres apparatus. The content of total
      phenolic compounds, flavonoids and flavonols was determined
      spectrophotometrically. Rosmarinic and salvianolic C acids were identified as the
      main antioxidants in C. grandiflora.

PMID- 22953892
TI  - Enzymatic synthesis and identification of oligosaccharides obtained by
      transgalactosylation of lactose in the presence of fructose using beta
      galactosidase from Kluyveromyces lactis.
AB  - The enzymatic transgalactosylation of lactose in the presence of fructose using
      beta-galactosidase from Kluyveromyces lactis (KlbetaGal) leading to the formation
      of oligosaccharides was investigated in detail. The reaction mixture was analyzed
      by high performance liquid chromatography with differential refraction detector
      (HPLC-RI) and two main transgalactosylation products were discovered. To
      elucidate their overall structures, the products were isolated and purified using
      preparative liquid chromatography and analyzed by LC/MS, one-dimensional (1D) and
      two-dimensional (2D) NMR studies. Allo-lactulose(beta-d-galactopyranosyl-(1->1)-d
      fructose) with two main isomers in D(2)O was identified to be the major
      transgalactosylation product while lactulose(beta-d-galactopyranosyl-(1->4)-d
      fructose) turned out to be the minor one, indicating that KlbetaGal was
      regioselective with respect to the primary C-1 hydroxyl group of fructose. The
      maximum yields of allo-lactulose and lactulose were 47.5 and 15.4g/l,
      respectively, at 66.5% lactose conversion (200g/l initial lactose concentration).

PMID- 22953893
TI  - Detection of postharvest changes of ascorbic acid in fresh-cut melon, kiwi, and
      pineapple, by using a low cost telemetric system.
AB  - The present paper deals with a novel telemetric device combined with a carbon
      amperometric sensor system to determine postharvest changes of ascorbic acid (AA)
      in fresh-cut fruits, without displacing products out of the storage rooms. The
      investigation was performed on kiwi, pineapple and melon, subjected to minimal
      processing, packaging, cold storage, and simulated shelf life. Results
      demonstrated that AA content of fresh-cut fruits of all species declines
      differently during storage. Cold storage notably reduced the degradation rate of
      AA in comparison with samples stored at 20 degrees C. The cold-chain interruption
      resulted in a sharp AA content reduction when the optimal storage condition was
      not rapidly replaced. Unpredicted results showed a high activity of oxidative
      enzymes, which prevented AA detection in melon samples. Our sensor system allowed
      us to demonstrate that both ascorbate peroxidase and ascorbate oxidase affected
      the oxidative stability and the nutritional quality of fresh cut melon fruits.

PMID- 22953894
TI  - Enrichment of eggs in n-3 polyunsaturated fatty acids by feeding hens with
      different amount of linseed oil in diet.
AB  - The production of n-3 polyunsaturated fatty acid enriched eggs by addition of
      linseed oil to the laying hens' diet has been evaluated in terms of production
      parameters and n-6/n-3 ratio. A total of 150 18weeks old Lohmann Brown laying
      hens were housed in cages and fed with basal diet and four experimental diets
      containing 1%, 2%, 3% or 4% of linseed oil added to the basal diet. The effect of
      the altered level of linseed oil on hens laying performance, fatty acid content
      and composition and cholesterol content in egg yolk has been evaluated during
      13weeks of experiment. Egg weight, yolk fat content, yolk weight, yolk percentage
      and shape index were not influenced by dietary treatment. The ratio between n-6
      and n-3 polyunsaturated fatty acids in eggs decreased in first 5weeks and then
      remained stable until the end of the experiment for all experimental groups.
      Different contents of linseed oil in feed highly influenced the n-6/n-3 ratio
      (P<0.0001). Addition of linseed oil did not influence the cholesterol content in
      yolks (P=0.5200) while the only factor affecting the cholesterol content was the
      hens age (P<0.0001).

PMID- 22953895
TI  - Authentication of Italian Espresso coffee blends through the GC peak ratio
      between kahweol and 16-O-methylcafestol.
AB  - Since the price of Arabica is currently more than twice higher than Robusta, a
      rapid and reliable method for the determination of the roasted coffee blend
      composition is fundamental for the authentication of commercial blends used for
      the Italian Espresso coffee. A GC-FID method based on the ratio between the
      integrated peak areas of kahweol (K) divided by the sum of K and 16-O
      methylcafestol (16MCF) was developed. No internal/external standard was used.
      Moreover, the quantitation of the unsaponifiable compounds is not necessary, as
      well as the calculation of any response factors. The percentage of Robusta in 34
      samples of coffee blends with known composition, and in 48 samples of pure
      varieties was used to build a cubic polynomial function with R(2)=0.998. The
      roasting conditions did not affect the results. Considering eight commercial
      blends (ranging 0-90% Robusta), no significant difference (two-tailed P=0.817)
      was registered between the claimed and the predicted composition.

PMID- 22953896
TI  - Human dietary exposure to perfluoroalkyl substances in Catalonia, Spain. Temporal
      trend.
AB  - In this study, we assessed the levels of 18 perfluoroalkyl substances (PFASs) in
      the most widely consumed foodstuffs in Catalonia, Spain, as well as the total
      dietary intake of these compounds. Forty food items were analysed. Only
      perfluoropentanoic acid (PFPeA), perfluorohexadecanoic acid (PFHxDA) and
      perfluorooctanoicdecanoic acid (PFOcDA) were not detected in any sample.
      Perfluorooctane sulfonate (PFOS) was the compound found in the highest number of
      samples (33 out of 80), followed by perfluorooctanoic acid (PFOA),
      perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS),
      perfluorodecanoic acid (PFDA) and perfluorodecane sulfonic acid (PFDS). Fish and
      shellfish was the food group in which more PFASs were detected and where the
      highest PFAS concentrations were found. The highest dietary intakes corresponded
      to children, followed by male seniors, with values of 1787 and 1466ng/day,
      respectively. For any of the age/gender groups of the population, the Tolerable
      Daily Intakes (TDIs) recommended by the EFSA were not exceeded. In general terms,
      PFAS levels found in the current study are lower than the concentrations recently
      reported in other countries.

PMID- 22953897
TI  - Quality of farmed and wild sea bass lipids studied by (1)H NMR: usefulness of
      this technique for differentiation on a qualitative and a quantitative basis.
AB  - Proton Nuclear Magnetic Resonance ((1)H NMR) spectroscopy was employed to study
      the lipids of farmed and wild European sea bass (Dicentrarchus labrax). This
      technique provided a great deal of detailed information on sea bass lipids
      composition and, once the spectra signals have been assigned, the simple
      observation of the spectra enables one to distinguish cultured from wild fish.
      This distinction is possible due to the presence in the former of high
      proportions of diunsaturated acyl groups, mainly linoleic. Furthermore, new
      approaches for quantitative characterization of sea bass lipids were developed.
      For the same season wild sea bass lipids contain not only higher molar
      percentages of omega-3 and of docosahexaenoic (DHA), but also higher
      concentrations of phosphatidylcholine and of cholesterol than farmed ones.
      However, in general, the absolute content of DHA and of eicosapentaenoic plus
      arachidonic (EPA+ARA) acyl groups as well as of phosphatidylcholine and
      cholesterol, were reasonably higher in farmed than in wild sea bass fillets, due
      to the higher total lipid content of the former. The presence of omega-1 acyl
      groups in all farmed samples and in some of the wild specimens was shown. As far
      as we know, this is the first time that omega-1 acyl groups have been identified
      and quantified in fish lipids by (1)H NMR.

PMID- 22953898
TI  - Prebiotic effects of yacon (Smallanthus sonchifolius Poepp. & Endl), a source of
      fructooligosaccharides and phenolic compounds with antioxidant activity.
AB  - Thirty-five different yacon (Smallanthus sonchifolius Poepp. & Endl) accessions
      were evaluated as potential alternative sources of fructooligosaccharides (FOS)
      and phenolic type natural antioxidants. FOS, total phenolics (TPC) and
      antioxidant capacity (AC) contents in the ranges of 6.4-65g/100g of dry mater
      (DM), 7.9-30.8mg chlorogenic acid (CAE)/g of DM and 23-136MUmol trolox
      equivalente (TE)/g DM were found. Accession AJC 5189 sparked attention for its
      high FOS content while DPA 07011 for its high TPC and AC. In addition, the
      prebiotic effect of yacon FOS was tested in vivo with a guinea pig model. A diet
      rich in yacon FOS promoted the growth of bifidobacteria and lactobacilli,
      resulting in high levels of short chain fatty acids (SCFAs) in the cecal material
      and enhancement of cell density and crypt formation in caecum tissue, being
      indicative of colon health benefits. This study allowed identification of yacon
      cultivars rich in FOS, AC and/or FOS and AC for nutraceutical applications.

PMID- 22953899
TI  - Effects of addition of egg ovotransferrin-derived peptides on the oxygen radical
      absorbance capacity of different teas.
AB  - Ovotransferrin-derived peptides showed synergistic effects with vitamin C,
      epigallocatechin gallate (EGCG), and caffeic acid, but not quercetin in our
      previous report. In this study, we further investigated the interactions between
      ovotransferrin-derived peptides and teas, based on the oxygen radical absorbance
      capacity (ORAC) assay. Our results showed that there was no significant
      difference in ORAC values among green, oolong, and black teas. For all the
      samples, 80% methanol extracts possessed better antioxidant capacity than hot
      water extracts. The antioxidant capacity of teas were improved by adding either
      ovotransferrin hydrolysate or its purified peptide IRW; however, adding
      hydrolysate did not improve antioxidant stability of teas. ORAC values of both
      teas and hydrolysate added teas were decreased during 22weeks of storage, while
      samples stored at 4 degrees C exhibited higher antioxidant capacity than those
      stored at room temperature. This suggested that ovotransferrin hydrolysate could
      be used as functional food ingredients in enhancing antioxidant capacities of
      foods, which would benefit human nutrition and health.

PMID- 22953900
TI  - A rapid method for detection of fumonisins B1 and B2 in corn meal using Fourier
      transform near infrared (FT-NIR) spectroscopy implemented with integrating
      sphere.
AB  - Fourier transform near infrared (FT-NIR) spectroscopy is an analytical procedure
      generally used to detect organic compounds in food. In this work the ability to
      predict fumonisin B(1)+B(2) contents in corn meal using an FT-NIR
      spectrophotometer, equipped with an integration sphere, was assessed. A total of
      143 corn meal samples were collected in Friuli Venezia Giulia Region (Italy) and
      used to define a 15 principal components regression model, applying partial least
      square regression algorithm with full cross validation as internal validation.
      External validation was performed to 25 unknown samples. Coefficients of
      correlation, root mean square error and standard error of calibration were 0.964,
      0.630 and 0.632, respectively and the external validation confirmed a fair
      potential of the model in predicting FB(1)+FB(2) concentration. Results suggest
      that FT-NIR analysis is a suitable method to detect FB(1)+FB(2) in corn meal and
      to discriminate safe meals from those contaminated.

PMID- 22953901
TI  - Microextraction by packed sorbent (MEPS) as a suitable selective method for l
      ascorbic acid determination in beverages.
AB  - In this study the modern microextraction by packed sorbent (MEPS) method followed
      by HPLC-UV analysis was optimised and evaluated for determination of l-ascorbic
      acid (AA) content in beverages. In this case 300MUL of sample was passed through
      silica BIN (barrel insert and needle assembly) and entrapped AA was eluted by
      60MUL of methanol-water (10%, v/v) solution. Recovery of the proposed method for
      three concentration levels ranged between 97.46% and 106.88% with relative
      standard deviation 8.7% (low conc.), 2.49% (medium conc.) and 1.98% (high).
      Obtained results of AA contents in real samples were in the ranges 56.5
      195.4MUg/mL and 130.4-1090.0MUg/mL for ice-tea and fruit juice samples,
      respectively. Proposed method was compared with iodometric titration and DPPH
      methods, but microextraction method was found to be more selective for AA
      determination in tested samples.

PMID- 22953902
TI  - Postharvest dehydration of wine white grapes to increase genistein, daidzein and
      the main carotenoids.
AB  - Wine white grape bunches of the Grechetto variety were dehydrated at 10, 20 and
      30 degrees C, RH 45% and forced air ventilation of 1.5m/s. Chemical and metabolic
      changes due to the effect of dehydration were studied at various stages of weight
      loss: 10%, 20%, 30% and 40%. Berry colour at 10 and 20 degrees C tended to become
      greener with dehydration but at 30 degrees C, at the final sampling, the colour
      darkened. Acidity decreased in all samples, while sugars increased. Total phenol
      content increased at 10 degrees C until 30% weight loss was reached and then
      declined, while at 20 and 30 degrees C the concentration decreased immediately.
      The contents of lutein and beta-carotene (respectively 68 and 58mg/kg d.w.),
      representing the 80% of total carotenoids, did not change significantly until the
      30% of weight loss, when at 30 degrees C the value increased above all for lutein
      while at 10 and 20 degrees C, the contents decreased significantly. Daidzein, at
      10 degrees C, rose significantly from about 150MUg/kg d.w. to 1434MUg/kg d.w. at
      20% weight loss and then declined; at the same weight loss percentage, the
      genistein concentration began to increase. At 20 degrees C both isoflavones rose
      until the end of the experiment, reaching values similar to the sample at 10
      degrees C. A temperature of 30 degrees C was deleterious to grape isoflavones. A
      discussion on the changes in isoflavones related to temperature and time is
      reported.

PMID- 22953903
TI  - Estimation of freezing storage time and quality changes in hake (Merluccius
      merluccius, L.) by low field NMR.
AB  - The potential of low field NMR (LF NMR) as a fast monitoring technique to
      estimate the quality of hake (Merluccius merluccius) frozen stored at -10 degrees
      C for up to 6months was evaluated. LF NMR clearly detected three populations of
      water: water strongly bound to macromolecules (T(2b)), trapped water (T(21)) and
      free water (T(22)). As storage time increased, and concomitant with an increase
      in the T(22) and a decrease in the T(21) water populations, the water holding
      capacity (WHC) and apparent viscosity values decreased and the shear strength
      increased, reflecting the characteristic loss of juiciness and tougher texture
      developed by hake during frozen storage. Two mathematical models were
      constructed: a simple regression using the biexponential analysis of the
      relaxation times (T(21), T(22)) and amplitudes (A(21), A(22)) and a partial least
      square regression (PLS) of CONTIN analysis. Both models seemed suitable to
      estimate the quality of the product.

PMID- 22953904
TI  - Effect of alkali treatment on structure and function of pea starch granules.
AB  - The effect of alkaline treatment on the structural and functional properties of
      pea starch granules was studied using a range of characterization methods
      including amylose content, scanning electron microscopy (SEM), X-ray diffraction
      (XRD), (13)C nuclear magnetic resonance (NMR), swelling power, differential
      scanning calorimetry (DSC), the Rapid Visco Analyser (RVA) and in vitro
      digestibility. The amylose content decreased by about 20-25% after 15days of
      alkaline treatment and there were small decreases in relative crystallinity and
      double helix content. Deformations were observed on the surface of alkali-treated
      granules, and there was evidence of adhesion between some of the granules. There
      was a 25-30% reduction in peak and final RVA pasting viscosities, but only a
      small reduction in swelling power. The endothermic transition of alkali-treated
      starch was broadened with a shift of the endothermic peak to higher temperature.
      However, the endothermic enthalpy remained largely unaffected. Alkali-treatment
      greatly increased the rate of in vitro enzymatic breakdown of the pea starch.
      More prolonged alkaline treatment for 30days did not cause further significant
      changes to the structural and functional properties of the starch granules. The
      effects of alkali on structure and function of pea starch are explained on the
      basis of limited gelatinization of the granules.

PMID- 22953905
TI  - Apoptotic effects of cooked and in vitro digested soy on human prostate cancer
      cells.
AB  - Previous laboratory and animal studies reported that soy isoflavones were major
      bioactive compounds in soy to exert chemoprotection of prostate cancer. However,
      these studies cannot reflect the realistic effects that soy may induce through
      diets, and little is known about the bioavailability of isoflavones from whole
      soy food and their bioactivities after cooking and digestion. In this study,
      cooking and in vitro digestion were used to prepare soy extracts and the effects
      of cooking and digestion on the isoflavone contents and bioactivities of the
      whole soy extracts were examined. The cooking procedure generally increased the
      amount of daidzin, genistin and daidzein, but decreased that of genistein.
      Digestion process significantly lowered contents of daidzin and genistin in 60min
      cooked sample, while increased the contents of daidzin and daidzein and decreased
      the content of genistein in the uncooked sample. Antioxidant activities of soy
      extracts increased after cooking and in vitro digestion, while no consistent
      increase of the four soy isoflavones was determined. The apoptotic effects of soy
      extracts on both LNCaP and C4-2B cells were generally in a dose-dependent manner.
      Compared to purified single isoflavones, cooked and digested soy were more
      effective on induction of prostate cancer cell apoptosis, which indicated
      synergistic interactions between various bioactive compounds in the whole soy.

PMID- 22953906
TI  - Identification of Baiying (Herba Solani Lyrati) commodity and its toxic
      substitute Xungufeng (Herba Aristolochiae Mollissimae) using DNA barcoding and
      chemical profiling techniques.
AB  - Baiying derived from Solanum lyratum Hance is a commonly consumed natural product
      for ethnomedical treatment of cancer. One of the substitutes present in the
      market is a carcinogenic aristolochic acids-containing herb Xungufeng derived
      from Aristolochia mollissima Thunb. The purpose of this study is to establish DNA
      barcodes, thin layer chromatography (TLC), high performance liquid chromatography
      (HPLC) and cytotoxicity assay to differentiate Baiying from Xungufeng. A total of
      30 DNA sequences from five DNA barcodes (ITS, matK, rbcL, trnH-psbA and trnL
      trnF) were generated to differentiate S. lyratum from A. mollissima and
      authenticate ten samples of Baiying and Xungufeng commodities. Using aristolochic
      acids as standard markers, TLC and HPLC analyses also successfully authenticated
      these commodities. In vitro cytotoxicity assay using HEK-293 and Vero cells
      demonstrated that Xungufeng was significantly more toxic than Baiying. This is
      the first study applying an integrated molecular, chemical and biological
      approach to differentiate traditional Chinese medicine from Aristolochia
      adulterant.

PMID- 22953907
TI  - Evaluation of hypolipidemic effects of peanut skin-derived polyphenols in rats on
      Western-diet.
AB  - The effect of water soluble polyphenolic extract of peanut skin (PE) was
      investigated for its hypolipidemic properties in rats on Western diet. Seven
      weeks old Wistar rats received control diet (AIN-93G), Western diet with and
      without a bolus of PE five times a week for 10weeks. Group which received
      300mg/kg body weight showed significantly reduced body weight and epididymal fat.
      Plasma and liver triglyceride (TG) and cholesterol (TC) levels were significantly
      reduced while faecal secretion of TG and TC was greatly increased upon PE
      administration. Liver mRNA expression of enzymes involved in fatty acid
      synthesis, such as fatty acid synthase (FAS), sterol receptor element binding
      protein (SREBP)-1c, acetyl-CoA carboxylase (ACC1) and lipid uptake genes, such as
      PPARgamma, were decreased, while PPARalpha was up-regulated by administration of
      PE. These data suggest that administration of PE may contribute to the improved
      lipid homoeostasis in rats on diets high in cholesterol and lipids.

PMID- 22953908
TI  - Degreening and postharvest storage influences 'Star Ruby' grapefruit (Citrus
      paradisi Macf.) bioactive compounds.
AB  - Ethylene is commercially used for artificial degreening of early season
      grapefruits. The present study investigated the effect of degreening and storage
      period on Star Ruby grapefruit (Citrus paradisi Macf.) bioactive compounds.
      Freshly harvested grapefruits were degreened in commercial packing shed for 60h
      using 2ppm of ethylene at a constant temperature of 20 degrees C. Both degreened
      and non-degreened (control) fruits were stored at 10 degrees C for 21days and
      later transferred to 20 degrees C for a period of 14days to simulate shipment and
      retail store market conditions. Bioactive compounds including carotenoids,
      limonoids, flavonoids and furocoumarins were analyzed using high performance
      liquid chromatography. Nomilin was significantly higher (P<0.05) in degreened
      fruits at 35days after storage. In contrast, flavonoids such as narirutin,
      naringin and poncirin were significantly (P<0.05) lower in degreened fruits at
      35days after storage. Degreening treatment reduced the levels of deacetyl
      nomilinic acid glucoside and bergamottin after 35days of storage; however, it had
      no significant effect on total soluble solids, decay, fruit softening, taste,
      odour, ascorbic acid, beta-carotene, lycopene, limonin, neohesperidin, didymin,
      6,7-dihydroxybergamottin, 5-geranyloxy-7-methoxycoumarin and radical scavenging
      activity. Therefore, degreening could be utilized to enhance the grapefruit
      aesthetic quality, with minimal effect on nutritional quality.

PMID- 22953909
TI  - Fast determination of N-phenylpropenoyl-l-amino acids (NPA) in cocoa samples from
      different origins by ultra-performance liquid chromatography and capillary
      electrophoresis.
AB  - N-Phenylpropenoyl-l-amino acids (NPA) are among the key contributors to the
      astringent taste of cocoa. Two fast and easy to use methods (CE and UPLC(r), both
      with PDA detection) for routine determination of the main NPA were developed.
      Crude extracts of defatted seeds were analysed by means of capillary
      electrophoresis leading to separation in less than 30min. Separation by means of
      UPLC(r) was much faster (<4min), however, a preceding SPE clean-up abolishes this
      benefit in time saving. Thus, the CE- and UPLC(r)-methods are comparable
      concerning time consumption and provide similar results. Analysis of 18 samples
      of raw and roasted beans from the global cocoa market originated from 12
      countries and 4 continents showed a great variability of NPA content (0.7
      3.6mg/g) and qualitative composition of different NPA. Anyway, all samples from
      cocoa beans showed a comparable NPA pattern. N-[3',4'-dihydroxy-(E)-cinnamoyl]-l
      aspartic acid was the most abundant metabolite, followed by N-[4'-hydroxy-(E)
      cinnamoyl]-l-aspartic acid and N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-l
      tyrosine (clovamide). The analysis of other plant organs (flowers, leaves,
      fruits) revealed an entirely different situation. NPA were detected in all parts
      of the fruit, with husk and pulp being clearly dominated by clovamide. In flowers
      and leaves no NPA were detected; 2-O-caffeoyltartaric acid was shown to be the
      major caffeic acid metabolite in leaves.

PMID- 22953910
TI  - Colour and surface fluorescence development and their relationship with Maillard
      reaction markers as influenced by structural changes during cornflakes
      production.
AB  - The aim of this work was to study colour and surface fluorescence development in
      relation to the chemical markers for the Maillard reaction at the cooking,
      flaking and toasting stages of cornflake production process. Colour was measured
      by a calibrated computer vision system. Surface fluorescence was measured on
      compressed samples. Aqueous extracted Maillard reaction markers
      (hydroxymethylfurfural, carboxymethyl-lysine, absorbance at 420nm and total
      fluorescence) were measured on protease hydrolyzed samples. Sample microstructure
      was observed by scanning electron microscopy. During cooking the colour
      coordinates L(*) and b(*) decreased and a(*) increased. After flaking, the
      samples appeared lighter, while the pigment concentration, fluorescence and
      hydroxymethylfurfural did not change. Toasting generated bubbles in the matrix
      and L(*) apparently increased, although brown pigment concentration increased.
      Pigment concentration did not correlate with surface colour due to the
      destruction or generation of interfaces. Surface and microstructure effects can
      be avoided by milling and compressing the samples.

PMID- 22953911
TI  - Development of a bioassay-coupled HPLC-SPE-ttNMR platform for identification of
      alpha-glucosidase inhibitors in apple peel (Malus *domestica Borkh.).
AB  - This work describes an analytical platform based on a high-resolution alpha
      glucosidase inhibition assay in combination with hyphenation of high-performance
      liquid chromatography, solid-phase extraction, and tube-transfer nuclear magnetic
      resonance spectroscopy, i.e., HPLC-SPE-ttNMR/high-resolution alpha-glucosidase
      assay. The platform enables fast screening for individual alpha-glucosidase
      inhibitory analytes in complex matrices, followed by structural identification
      targeted these alpha-glucosidase inhibitors, as demonstrated by a proof-of
      concept study with extract of 'Pink Lady' apple peel. A scout-separation produced
      a high-resolution biochromatogram and a HPLC chromatogram, which were used for
      pinpointing HPLC peaks displaying alpha-glucosidase inhibition. Active analytes
      were cumulatively trapped on SPE cartridges and the structures identified by (1)H
      NMR experiments obtained in the HPLC-SPE-ttNMR mode. (-)-Epicatechin (1),
      reynoutrin (3) and avicularin (4) were identified as active compounds. IC(50) of
      the active compounds were determined along with six structurally related
      compounds. Quercetin was the most potent inhibitor with an IC(50) of 8.1+/
      0.4MUM. The platform proved to be an efficient method for the identification of
      alpha-glucosidase inhibitors.

PMID- 22953912
TI  - Evaluation of mutagenic and antimutagenic activities of oligorutin and
      oligoesculin.
AB  - Rutin and esculin have been polymerised by laccase. Five fractions with M(w)-
      between 2127.42 and 8331.85g/mol for oligorutins, and between 688.12 and
      6973g/mol for oligoesculins, were obtained. Fourier transformed infrared analysis
      showed that oligorutins were formed through C-C, C-O and CO linkages, while
      oligoesculins were obtained through C-C linkages. Monomers, their oligomers and
      their metabolites exhibited no mutagenic effect. Oligorutins and oligoesculins
      were more efficient in reducing the mutagenicity of methyl methanesulphonate, by,
      respectively, 69% and 64.8% in the presence of Salmonella typhimurium TA104, and
      79.7% and 68.9% in the presence of S. typhimurium TA102, than were their
      monomers. The same oligomers revealed greater significant inhibitory effect of 2
      aminoanthracene mutagenicity (respectively 82.4% and 79.3% in the presence of S.
      typhimurium TA104, and 89.2% and 82.9% in the presence of S. typhimurium TA102),
      than their monomers. Our results strongly suggest the enhancement of the tested
      monomer antimutagenicity after polymerisation.

PMID- 22953913
TI  - Hydrolyzable tannin analysis in food.
AB  - The discovery of plant polyphenols in food is perhaps one of the biggest
      breakthroughs in modern food science. Plant polyphenols are known for their role
      in food quality and safety, since they contribute significantly to taste,
      flavour, colour, stability etc., while they are increasingly recognised as
      important factors in long-term health, contributing towards reducing the risk of
      chronic disease. Almost 200years ago, hydrolyzable tannins (HTs) were the first
      group of plant polyphenols subjected to analytical chemical research. Despite the
      lack of commercially available standards, food analysis research offers a wealth
      of papers dealing with extraction optimisation, identification and quantification
      of HTs. The object of this review is to summarise analytical chemistry
      applications and the tools currently used for the analysis of HTs in food.

PMID- 22953914
TI  - Lipid characteristics of two subtropical Seriola fishes, Seriola dumerili and
      Seriola rivoliana, with differences between cultured and wild varieties.
AB  - The lipid and fatty acid compositions of the muscle and liver of two subtropical
      Seriola fish species, Seriola dumerili and Seriola rivoliana, were investigated.
      The lipid levels of cultured S. dumerili were significantly higher than were
      those of the wild ones. Triacylglycerols and phospholipids were the dominant
      lipids of both the cultured and wild. In both species, the major fatty acids in
      the muscle and liver triacylglycerols were 14:0 (cultured), 16:0, 18:0, 16:1n-7,
      18:1n-7, 18:1n-9, 18:2n-6 (linoleic acid: LA, cultured), 20:5n-3, and 22:6n-3. In
      spite of similar levels of many of the fatty acids between cultured and wild
      triacylglycerols, the cultured samples had markedly higher levels of LA with
      trace levels of 20:4n-6 (arachidonic acid: ARA) and 22:5n-6, while the wild ones
      had very low 18:2n-6 levels with small levels of ARA and 22:5n-6. The ratio
      (R(LA/ARA)) of LA to ARA in the cultured samples was markedly higher than were
      those of the wild samples.

PMID- 22953915
TI  - Polymorphism, microstructure and rheology of butter. Effects of cream heat
      treatment.
AB  - The effect of cream heat treatment prior to butter manufacturing, fluctuating
      temperatures during storage and presence of fat globules vs. no fat globules was
      examined in laboratory scale produced butter. X-ray diffraction and differential
      scanning calorimetry was used to study crystallization behaviour and nuclear
      magnetic resonance to measure solid fat content and water droplet size
      distribution. Furthermore, the crystal structure was linked to the rheological
      properties and microstructure of the butter using confocal laser scanning
      microscopy. Butter produced from non-matured cream mainly formed alpha- and beta'
      crystals with minor traces of beta-crystals. Maturing of the cream caused a
      transition from alpha- to beta'- and beta-form. The rheological behaviour of slow
      cooled butter deviated from the matured ones by having a lower elastic modulus,
      caused by a weaker crystal network. Presence of fat globules did not affect the
      rheological properties significantly.

PMID- 22953916
TI  - The potential of extracts of Caryocar villosum pulp to scavenge reactive oxygen
      and nitrogen species.
AB  - Caryocar villosum (piquia) is a native fruit from the Amazonian region,
      considered to be an interesting source of bioactive compounds. In this paper,
      five extracts of C. villosum pulp were obtained, using solvents with different
      polarities and their in vitro scavenging capacity against reactive oxygen species
      (ROS) and reactive nitrogen species (RNS) was determined. Additionally, the
      phenolic compounds and carotenoids in each extract were identified and quantified
      by a high performance liquid chromatography coupled to diode array and mass
      spectrometer detectors (HPLC-DAD-MS/MS). The ethanol/water and water extracts,
      which presented the highest phenolic contents (5163 and 1745MUg/g extract,
      respectively), with ellagic acid as the major phenolic compound, proved to have
      the highest ROS and RNS scavenging potential. Nevertheless, in general, ellagic
      acid was less effective in scavenging ROS (IC(50) from 1.7 to 108MUg/ml) and RNS
      (IC(50) from 0.05 to 0.59MUg/ml), when compared to gallic acid (IC(50) from 0.4
      to 226MUg/ml for ROS and IC(50) from 0.04 to 0.12MUg/ml for RNS). The results
      obtained in the present study clearly demonstrated that the in vitro antioxidant
      efficiency of C. villosum extracts was closely related to their contents of
      phenolic compounds.

PMID- 22953917
TI  - NIR technology for on-line determination of superficial a(w) and moisture content
      during the drying process of fermented sausages.
AB  - Three different NIR equipment were evaluated based on their ability to predict
      superficial water activity (a(w)) and moisture content in two types of fermented
      sausages (with and without moulds on surface), using partial least squares (PLS)
      regression models. The instruments differed mainly in wavelength range,
      resolution and measurement configuration. The most accurate equipment was used in
      a new experiment to achieve robust models in sausages with different salt
      contents and submitted to different drying conditions. The models developed
      showed determination coefficients (R(2)(P)) values of 0.990, 0.910 and 0.984, and
      RMSEP values of 1.560%, 0.220% and 0.007% for moisture, salt and a(w)
      respectively. It was demonstrated that NIR spectroscopy could be a suitable non
      destructive method for on-line monitoring and control of the drying process in
      fermented sausages.

PMID- 22953918
TI  - Instant food products as a source of silicon.
AB  - Silicon is a trace element for humans, and is absorbed from food in the form of
      orthosilicic acid. Instant food products are part of a constantly growing market
      of convenience foods, which have not been evaluated yet as sources of silicon. In
      this study the total and soluble silicon contents in different instant food
      products were determined by using graphite furnace atomic absorption spectrometry
      (GF-AAS). A selection of instant products commercially available in Wroclaw were
      analyzed: soups, main courses, coffee drinks, jellies and puddings. Total silicon
      contents in soups, main courses and coffee drinks ranged widely and reached the
      values: 0.10-30.20, 0.63-37.91 and 0.21-13.37mg/serving, respectively. These
      products contained 0.05-1.26mg of soluble silicon per serving. The total silicon
      content in jellies and puddings did not exceed 0.36mg and 2.42mg/serving,
      respectively. Among the analyzed desserts the highest level of soluble silicon
      was found in chocolate puddings: 0.36-0.41mg/serving. The silicon level in
      servings of the studied instant products when prepared with the appropriate
      amount of water was also estimated. The mean content of silicon determined in
      samples of drinking water from Wroclaw and the vicinity, which was used for the
      estimation, amounted to 7.09mg/l. The total silicon content in ready-to-eat
      products ranged from 1.32 to 39.21mg/serving. In conclusion, some of the analyzed
      instant foods contained very high amounts of silicon, however the content of the
      soluble, and hence available, form of this element was low.

PMID- 22953919
TI  - In vitro attenuation of acrolein-induced toxicity by phloretin, a phenolic
      compound from apple.
AB  - In the current study, the protective effects of phloretin were investigated in
      acrolein-challenged amino acid, protein, and cell models. It was found that the
      formation of FDP-lysine (a typical acrolein-lysine adduct) was strongly inhibited
      in the presence of phloretin and the remaining electrophilic site in FDP-lysine
      was also blocked by phloretin. Moreover, direct trapping of acrolein by phloretin
      was found to be responsible for inhibiting the incorporation of carbonyl groups
      into BSA and oligomerisation in RNase A. Subsequently, the reduction of LDH
      release in human neuroblastoma SH-SY5Y cells under acrolein challenge suggested
      the cytoprotective effects of phloretin. Such protection might be mediated
      through inhibiting the increased cellular protein carbonyl level as revealed by
      Western blotting analysis. The present study highlighted an apple phenolic
      compound, phloretin as a promising candidate in prevention or treatment of
      acrolein-associated human diseases.

PMID- 22953920
TI  - Heat-oxidation stability of palm oil blended with extra virgin olive oil.
AB  - Rancimat induction time of palm oil (PO), several extra virgin olive oils (EV)
      and their binary blends have been determined at three different temperatures
      (120, 130 and 140 degrees C). Analytical composition and oxidation stability of
      PO/EV blends were found to be a linear combination of the oil partners. Induction
      time of pure PO was always higher than those of EV oils and blends, in which
      induction time increased proportionally with the percentage of PO. However,
      induction time of 80% PO blend was similar to that of pure PO. Fatty acid
      composition appeared to be the most important factor affecting heat-oxidation
      stability and a saturated/unsaturated ratio near 1 was the optimally stable
      composition. Conversely, total phenols had a zero or negative role on the
      oxidative stability of the blends. Finally, in heat-oxidised oils significant
      losses of polyunsaturated fatty acids and formation of short-chain fatty acids
      were recorded.

PMID- 22953921
TI  - Phospholipid fingerprints of milk from different mammalians determined by 31P
      NMR: towards specific interest in human health.
AB  - Our objective was to identify and quantify phospholipids in milk from different
      species (human HM, cow CoM, camel CaM, and mare MM) using an optimised (31)P NMR
      spectroscopy procedure. The phospholipid fingerprints were species-specific with
      a broader variety of classes found in HM and MM; HM and CaM were richer in
      sphingomyelin (78.3 and 117.5MUg/ml) and plasmalogens (27.3 and 24MUg/ml),
      possibly important for infant development. Total phospholipid content was higher
      in CaM (0.503mM) and lower in MM (0.101mM) compared to HM (0.324mM) or CoM
      (0.265mM). Our optimised method showed good sensitivity, high resolution, and
      easy sample preparation with minimal loss of target molecules. It is suitable for
      determining the accurate composition of a large number of bioactive phospholipids
      with putative health benefits, including plasmalogens, and should aid in
      selecting appropriate ingredient sources for infant milk substitutes or
      fortifiers, and for functional foods dedicated to adults.

PMID- 22953923
TI  - Characterization of Spanish honeys with protected designation of origin "Miel de
      Granada" according to their mineral content.
AB  - Honey attributes such as geographical origin or specified botanical sources often
      command a premium price due to their organoleptic or pharmacoactive properties.
      "Miel de Granada" is a highly quality product with protected designation of
      origin (PDO) which includes six monofloral honeys and two multifloral honeys. Our
      objective was the characterization of "Miel de Granada" according to their metal
      content. Metal content was specific enough and allowed discrimination from honeys
      of different botanical and geographical origins and confirmed the authenticity of
      PDO labelling as Granada product with the determination of only five elements (K,
      Na, Ca, Mg and Zn). Chemometric techniques as cluster analysis and ANOVA were
      used to classify honeys according to their botanical and geographical origin in
      the metal data. Metal content marks the differences in honey samples and can be
      used as a tool to assess the quality of honeys. ANOVA showed significant
      differences among rosemary honeys from different geographical areas despite the
      botanical factor weight. Our research contributes to the groundwork studies to
      determine the geographical origin of Spanish honeys.

PMID- 22953924
TI  - Antioxidant and metal chelating activities of peptide fractions from phaseolin
      and bean protein hydrolysates.
AB  - Bean protein isolate and phaseolin were hydrolysed using pepsin and pancreatin,
      and the resulting hydrolysates were filtered through a 1kDa cut-off membrane and
      fractionated by size exclusion chromatography. Three fractions corresponding to
      MW 0.7-1.0kDa, 0.43-0.7kDa and <0.43kDa (A1, A2, and A3 for protein isolate
      fractions, and B1, B2, and B3 for phaseolin fractions) were assayed for
      antioxidant and metal chelating activity and they were also subjected to amino
      acid and SDS-PAGE analysis. Fractions A1 and B1 had the highest copper chelating
      activity (78% and 82%, respectively), while iron chelating activity was the
      highest in fractions A1 and B3 (36% and 16%, respectively). Fractions A2 and B3
      had the highest antioxidant activity as determined by inhibition of reducing
      power and beta-carotene bleaching, while the highest ABTS radical scavenging
      activity was found in A3 and B3. Thus, fractions coming from the isolate and
      phaseolin had similar activities except for iron chelation, suggesting that
      phaseolin is the major contributor to the antioxidant and copper chelating
      activities of the hydrolysed protein isolate.

PMID- 22953925
TI  - Enantiomeric and non-enantiomeric monoterpenes of Juniperus communis L. and
      Juniperus oxycedrus needles and berries determined by HS-SPME and
      enantioselective GC/MS.
AB  - For the first time, enantiomeric and non-enantiomeric distribution of
      monoterpenes in the headspace of Juniperus communis L. and Juniperus oxycedrus
      needles and berries has been determined using HS-SPME combined with
      enantioselective GC/MS. The essential oils from needles and berries of both
      Juniperus species obtained by hydrodistillation were also performed. HS-SPME has
      shown good potential to reproduce the same results as the commonly used
      hydrodistillation extraction technique. While needles and berries of J. communis
      showed high contents of sabinene, alpha-pinene and beta-myrcene with 19-30%, 12
      24% and 9-20%, respectively, J. oxycedrus was strongly dominated by alpha-pinene
      with 85-92% in both needles and berries. Large variations in chiral distribution
      of monoterpenes within the same plant species and between the two junipers were
      observed. Interestingly, similar enantiomeric preferences of monoterpenes were
      obtained between needles and berries of the two junipers.

PMID- 22953926
TI  - Rapid detection of lipid oxidation in beef muscle packed under modified
      atmosphere by measuring volatile organic compounds using SIFT-MS.
AB  - The objective of this work was to evaluate the use of a direct analysis technique
      (SIFT-MS) to measure the lipid oxidation process in beef meat packed under high
      oxygen atmosphere and compare it to conventional techniques such as gas
      chromatography-mass spectrometry analysis and TBARS values. Meat samples from two
      suppliers were selected and packaged under the same atmosphere conditions. The
      fatty acid content, the physicochemical (TBARS and volatile compounds) and
      sensory parameters were measured. The samples from supplier 2 had a highest
      content of PUFA and n6 fatty acids that was related with a highest oxidation
      during storage. SIFT-MS and SPME-GC-MS detected a significant increase for most
      of the volatiles compounds analyzed during storage especially, in aldehyde
      compounds. High correlation coefficients between TBARS values and linear
      aldehydes (C3-C7) measured by both techniques were obtained and this indicates
      that SIFT-MS can be used to monitor lipid oxidation changes.

PMID- 22953927
TI  - Effect of heat treatment of rennet skim milk induced coagulation on the
      rheological properties and molecular structure determined by synchronous
      fluorescence spectroscopy and turbiscan.
AB  - Heat treatment applied to milk induces denaturation of whey proteins, leading to
      a complex mixture of whey protein and whey protein coated casein micelles. The
      present paper investigates the effects of heat treatment (60 and 80 degrees C
      during 20min) and rennet-induced coagulation temperature (30 and 40 degrees C)
      determined by rheology, synchronous fluorescence spectroscopy (SFS) and turbiscan
      measurements. The gelation times determined by rheology and SFS increased with
      the increase of heat treatment applied to milk. The rise in temperature induced a
      decrease in the maximum curd firming rate and an increase in the viscosity of the
      investigated milk samples. The principal component analysis (PCA) applied,
      separately, to the SF and turbiscan spectra showed a clear discrimination
      between: (i) raw milks and heated milks; and (ii) milks renneted at 30 degrees C
      from those renneted at 40 degrees C. The results showed the ability of SFS as a
      rapid and non-destructive technique for the: (i) monitoring network structure and
      molecular interaction during the coagulation process; and (ii) determination of
      gelation time of rennet-induced coagulation of studied milk samples.

PMID- 22953928
TI  - Purification, partial characterization and anti-inflammatory characteristics of
      lotus (Nelumbo nucifera Gaertn) plumule polysaccharides.
AB  - A novel lotus plumule polysaccharide (LPPS) was purified, characterised and
      cultured with RAW264.7 macrophages to evaluate its anti-inflammatory
      characteristics. LPPS was purified using Sepharose 6B gel filtration and
      dissolved into two major components, fraction-1 (F1) and fraction-2 (F2). The
      molecular weights of native F1 and F2 were approximately distributed at >2,000
      and 25.7kDa, respectively. The total protein and carbohydrate constituent ratios
      in LPPS, F1, and F2 were 30.0+/-0.9% vs. 70.0+/-0.9%, 30.1+/-2.6% vs. 69.9+/
      2.6%, and 96.5+/-6.1% vs. 3.5+/-6.1% (w/w), respectively, suggesting that F1 may
      be a major proteo-polysaccharide component and F2 a glycoprotein constituent in
      LPPS. Pro-/anti-inflammatory (IL-6/IL-10) cytokine secretion ratios by
      lipopolysaccharide-stimulated RAW264.7 macrophages were significantly decreased
      by F1 and F2 treatments, particularly by F2, in a dose-dependent manner under a
      preventive experimental model. This study suggests that purified components, F1
      and F2 from LPPS, have strong anti-inflammatory effects on LPS-induced inflamed
      macrophages in a preventive manner.

PMID- 22953929
TI  - Evaluation of green coffee beans quality using near infrared spectroscopy: a
      quantitative approach.
AB  - Characterisation of coffee quality based on bean quality assessment is associated
      with the relative amount of defective beans among non-defective beans. It is
      therefore important to develop a methodology capable of identifying the presence
      of defective beans that enables a fast assessment of coffee grade and that can
      become an analytical tool to standardise coffee quality. In this work, a
      methodology for quality assessment of green coffee based on near infrared
      spectroscopy (NIRS) is proposed. NIRS is a green chemistry, low cost, fast
      response technique without the need of sample processing. The applicability of
      NIRS was evaluated for Arabica and Robusta varieties from different geographical
      locations. Partial least squares regression was used to relate the NIR spectrum
      to the mass fraction of defective and non-defective beans. Relative errors around
      5% show that NIRS can be a valuable analytical tool to be used by coffee
      roasters, enabling a simple and quantitative evaluation of green coffee quality
      in a fast way.

PMID- 22953930
TI  - Study on the interaction of food colourant quinoline yellow with bovine serum
      albumin by spectroscopic techniques.
AB  - The interaction of a food colourant, quinoline yellow (Qy), and bovine serum
      albumin (BSA) was investigated by spectrophotometry, spectrofluorometry, FT-IR
      and circular dichroism (CD) techniques. The experimental results indicated that
      the quenching mechanism of BSA by the dye was a static procedure. Various binding
      parameters were evaluated. The negative value of DeltaH, negative value of DeltaS
      and the negative value of DeltaG indicated that van der Waals force and hydrogen
      bonding play major roles in the binding of Qy and BSA. Based on Forster's theory
      of non-radiation energy transfer, the binding distance, r, between the donor
      (BSA) and acceptor (Qy) was evaluated. The results of CD and UV-vis spectroscopy
      showed that this dye could bind to BSA and the conformation of BSA changed.

PMID- 22953931
TI  - Human IgE binding and in vitro digestion of S-OVA.
AB  - S-OVA, a more thermostable form of ovalbumin (OVA), was formed from native OVA or
      egg white in vitro, by heating at high pH, and by storage at low temperatures. S
      OVA showed a much lower reactivity against IgE than OVA, although this difference
      in IgE binding was minimized after simulated gastro intestinal digestion, despite
      S-OVA was more resistant to proteolysis, particularly to pepsin, than its native
      form. It is, therefore, likely that the transformation of OVA to S-OVA does not
      affect its ability to sensitise or trigger allergic reactions at the duodenal
      level. These results are discussed in the light of the described conformational
      changes reported to occur in the transition between OVA and S-OVA.

PMID- 22953932
TI  - Caseinolytic and milk-clotting activities from Moringa oleifera flowers.
AB  - This work reports the detection and characterization of caseinolytic and milk
      clotting activities from Moringa oleifera flowers. Proteins extracted from
      flowers were precipitated with 60% ammonium sulphate. Caseinolytic activity of
      the precipitated protein fraction (PP) was assessed using azocasein, as well as
      alpha(s)-, beta- and kappa-caseins as substrates. Milk-clotting activity was
      analysed using skim milk. The effects of heating (30-100 degrees C) and pH (3.0
      11.0) on enzyme activities were determined. Highest caseinolytic activity on
      azocasein was detected after previous incubation of PP at pH 4.0 and after
      heating at 50 degrees C. Milk-clotting activity, detected only in the presence of
      CaCl(2), was highest at incubation of PP at pH 3.0 and remained stable up to 50
      degrees C. The pre-treatment of milk at 70 degrees C resulted in highest clotting
      activity. Enzyme assays in presence of protease inhibitors indicated the presence
      of aspartic, cysteine, serine and metallo proteases. Aspartic proteases appear to
      be the main enzymes involved in milk-clotting activity. PP promoted extensive
      cleavage of kappa-casein and low level of alpha(s)- and beta-caseins hydrolysis.
      The milk-clotting activity indicates the application of M. oleifera flowers in
      dairy industry.

PMID- 22953933
TI  - Direct characterization of commercial lecithins by easy ambient sonic-spray
      ionization mass spectrometry.
AB  - Commercial lecithins are composed mainly of phospholipids and triacylglycerols.
      The analysis of the commercial lecithins, including their fraction of
      phospholipids, normally involves laborious and expensive protocols. Easy ambient
      sonic-spray ionization mass spectrometry (EASI-MS) is shown to be an efficient
      technique for the analysis of lipids. Samples of commercial lecithins including
      standards, refined, deoiled and modified soy lecithin were tested. Characteristic
      profiles of phosphatidylcholines and triacylglycerols are detected by EASI(+)-MS,
      whereas EASI(-)-MS provided phosphatidylethanolamines, glycophospholipids and
      free fatty acids profiles. Acetylated lecithins also displayed characteristic
      acetylated derivatives. EASI-MS data was also compared to MALDI-MS, and found to
      display richer compositional information. The industrial process applied to
      lecithin fabrication was also characterised via typical EASI-MS profiles. EASI-MS
      both in its positive and negative ion modes offers a direct, fast and efficient
      technique able to characterise commercial lecithin.

PMID- 22953934
TI  - "Extraction and safety of stevioside"; response to the article "Stevia rebaudiana
      Bertoni, source of a high potency natural sweetener: a comprehensive review on
      the biochemical, nutritional and functional aspects".

PMID- 22953935
TI  - HPLC-PDA-MS fingerprinting to assess the authenticity of pomegranate beverages.
AB  - HPLC with fluorescence, PDA and mass spectrometric detection were used to analyse
      the (poly)phenol content of a Bordeaux red wine, POM Wonderful pomegranate juice
      and three other beverages advertised as being made from 100% pomegranate juice.
      The red wine and POM Wonderful juice contained characteristic anthocyanin
      profiles with the latter also being characterised by the presence of
      ellagitannins and the former by flavan-3-ols monomers and procyanidin dimers and
      trimers. The three other pomegranate products all contained the expected
      ellagitannins but their anthocyanin profiles were a mixture of red wine and
      pomegranate anthocyanins. They also contained flavan-3-ol monomers and
      procyanidin dimers and trimers, components not usually detected in 100%
      pomegranate beverages. The HPLC-based procedures, therefore, provide a straight
      forward means of accessing the authenticity of pomegranate-based products with
      the ready detection of constituents derived from red grapes.

PMID- 22953936
TI  - Type of packaging affects the colour stability of vitamin E enriched beef.
AB  - Colour stability is a very important parameter for meat retail display, as
      appearance of the product is the deciding factor for consumers at time of
      purchase. This study investigated the possibility of extending appearance shelf
      life through the combined use of packaging method (overwrapping - OVER, modified
      atmosphere - MAP, vacuum skin packaging - VSP and a combination of modified
      atmosphere and vacuum skin packaging - MAPVSP) and antioxidants (vitamin E
      enriched beef). Retail attributes (appearance, lean colour, % surface
      discolouration), as well as colour space analysis of images for red, green and
      blue parameters were measured over 18days. MAPVSP provided the most desirable
      retail appearance during the first 4days of retail display, while VSP-HB had the
      best colour stability. Overall, packaging type was more influential than alpha
      tocopherol levels on meat colour stability, although alpha-tocopherol levels
      (>4MUgg(-1) meat) had a protective effect when using high oxygen packaging
      methods.

PMID- 22953937
TI  - Human health risk of dietary intake of organochlorine pesticide residues in
      bovine meat and tissues from Veracruz, Mexico.
AB  - Tissue distribution patterns of organochlorine pesticides in bovine carcasses
      varied significantly among seasons, geographic locations and tissues. The highest
      concentrations of Sigma-DDT during the dry season were detected in lungs from
      Paso de Ovejas (2,834.90MUg/kg lipid) and, during the rainy season, Lindane and
      Sigma-HCH in muscle and lung samples from Paso de Ovejas (995.80 and
      1,690.10MUg/kg lipid). Estimated daily intakes of gamma-HCH and Sigma-DDT (3.35
      and 1.22MUg/kg bw/day) through consumption of muscle tissues from Paso de Ovejas
      and Puente Nacional during the rainy season showed the highest contribution.
      During the rainy season the highest non-cancer Hazard Ratios estimated
      corresponded to gamma-HCH (3.97) and Sigma-DDT (4.39) detected in muscle samples
      from Puente Nacional. The highest Hazard Ratios of cancer risk to the 95th
      centile daily consumption through meat corresponded to p,p'-DDT from Alvarado
      (7.76E+06) and from Paso de Ovejas for gamma-HCH (1.50E+05) during rainy season.
      The results indicate potential non- and carcinogenic risks to consumer health
      through meat consumption.

PMID- 22953938
TI  - Sensitive fluorescent detection of melamine in raw milk based on the inner filter
      effect of Au nanoparticles on the fluorescence of CdTe quantum dots.
AB  - A simple, rapid and sensitive fluorescent assay for determination of melamine has
      been developed based on inner filter effect (IFE) of gold nanoparticles (AuNPs)
      on the fluorescence of CdTe quantum dots (QDs). When thioglycolic acid-capped
      CdTe QDs was mixed with citrate-stabilized AuNPs, the fluorescence of CdTe QDs
      was significantly quenched via the IFE of AuNPs. With the presence of melamine,
      melamine could induce the aggregation and corresponding absorbance change of
      AuNPs, which then resulted in the recovery of IFE-decreased emission of CdTe QDs.
      Under the optimum conditions, the detection limit for melamine in raw milk was
      0.02mgL(-1). The application of this method in samples of melamine-spiked raw
      milk suggested a recovery between 103% and 104%. Therefore, the obvious merits
      provided by the present assay, such as simplicity, rapidity, low cost, and high
      sensitivity, would make it promising for on-site screening of melamine adulterant
      in raw milk.

PMID- 22953939
TI  - Fast and simple extraction of pesticide residues in selected fruits and
      vegetables using tetrafluoroethane and toluene followed by ultrahigh-performance
      liquid chromatography/tandem mass spectrometry.
AB  - An extraction and analytical method for the determination of pesticide residues
      in fruits and vegetables has been developed. The method includes extraction with
      a pressurised liquid solvent containing a mixture of 1,1,1,2-tetrafluoroethane
      and toluene, and identification/quantification of pesticides using ultrahigh
      performance liquid chromatography coupled to tandem mass spectrometry
      (UPLC/MS/MS). Validation studies were carried out to evaluate the performance of
      the method for the determination of 71 different pesticides and metabolites in
      tomato, cucumber, pepper, spinach, zucchini, grape, cherry, peach and apricot.
      Matrix-matched calibration curves were applied and correlation coefficients
      (r(2)) came out to be greater than 0.99. Limit of quantification (LOQ) values of
      the active substances were found to be lower than the maximum residue limits
      (MRL) according to regulations in Turkey. The recovery values were found to be
      between 70% and 120% with relative standard deviations less than 20%. Based on
      these results, the proposed method is fast, cheaper, rugged and gives
      quantitative results with no additional clean-up steps.

PMID- 22953940
TI  - Antioxidant activity of Lactobacillus plantarum strains isolated from traditional
      Chinese fermented foods.
AB  - Eleven Lactobacillus plantarum strains isolated from traditional Chinese
      fermented foods were investigated for their in vitro scavenging activity against
      hydroxyl and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and their
      resistance to hydrogen peroxide. L. plantarum C88 at a dose of 10(10) CFU/ml
      showed the highest hydroxyl radical and DPPH scavenging activities, with
      inhibition rates of 44.31% and 53.05%, respectively. Resistance of intact cells
      to hydrogen peroxide was also found in all strains. L. plantarum C88 was the most
      resistant strain against hydrogen peroxide. When L. plantarum C88 was
      administered to senescent mice suffering oxidative stress induced by d-galactose,
      the serum superoxide dismutase activity, the glutathione peroxidase activity and
      the total antioxidant capacity in liver increased significantly, while the level
      of malondialdehyde in liver decreased significantly. L. plantarum C88 isolated
      from traditional Chinese fermented dairy tofu could be considered as a potential
      antioxidant to be applied in functional foods.

PMID- 22953941
TI  - Vitamin C induces apoptosis in AGS cells by down-regulation of 14-3-3sigma via a
      mitochondrial dependent pathway.
AB  - Ascorbic acid (vitamin C) is an essential component of most living cells. Apart
      from antioxidant activity, it has been reported to inhibit cancer cell growth in
      vitro in human cancer cells. However, the cellular mechanism underlying
      anticancer activity has not been fully elucidated. In this study, vitamin C
      showed a cytotoxic effect on human gastric cancer cell line AGS (LD50 300MUg/ml).
      Further, flow cytometry analysis showed that vitamin C increased the sub-G1
      (apoptosis) population and apoptosis confirmed by fluorescein isothiocyanate
      Annexin V double staining in AGS cells. Moreover, specific immuno-blotting
      revealed the expression of the phosphorylated form of Bad (S136), 14-3-3sigma,
      pro-caspases-3, -6, -8, and-9 protein levels were significantly decreased and
      Bax/Bcl-xL ratio was increased in a dose-dependent manner. Also, wound healing
      assay results showed that vitamin C inhibited AGS cell proliferation. These
      findings suggest that vitamin C induces apoptosis and might be a potential
      therapeutic agent for gastric cancer.

PMID- 22953942
TI  - Antioxidant and alpha-glucosidase inhibitory phenolics isolated from highbush
      blueberry flowers.
AB  - Blueberries have been extensively researched, but there are limited studies on
      other parts of the plant. Here we report the first phytochemical examination of
      highbush blueberry (Vaccinium corymbosum) flowers, which yielded 21 phenolics.
      The compounds were identified from extensive NMR and mass spectral analyses and
      included five caffeic acid (1-5), three coumaric acid (6-8), and two cinnamyl
      alcohol (9-10) derivatives, eight flavonol glycosides (11-18), and three
      phenylpropanoid-substituted catechins (19-21). The isolates were evaluated for
      antioxidant and alpha-glucosidase inhibitory activities. Overall, the flavonol
      glycosides and phenylpropanoid-substituted catechins showed superior antioxidant
      activities compared to the positive controls, vitamin C (IC(50)=63MUM) and
      butylated hydroxytoluene (IC(50)=1548MUM). Similarly, these phenolic sub-classes
      were more potent alpha-glucosidase inhibitors than the clinical drug, acarbose
      (IC(50)=200MUM). Thus, non-consumed parts of food plants may be exploited as
      sources of bioactive compounds beyond their edible parts alone for nutraceutical
      and functional food applications.

PMID- 22953943
TI  - Folate in oats and its milling fractions.
AB  - Total folate content in oat varieties from three harvesting years (2006-2008),
      and in oats milling fractions, was determined using microbiological assay.
      Furthermore, folate vitamer distribution in milling fractions were examined with
      the UPLC method, which was taken in use and validated. The total folate content
      of the cultivars varied moderately within each year. The average content in the
      2008 samples was 685ng/gdm. The UPLC method proved fast and sensitive for
      determining seven folate monoglutamates in cereal samples. Folate content in
      fractions, which are normally discarded, such as flour from oat cutting and
      flaking, were 1.5- to 2.5-fold higher than in native grain. The main folate
      vitamers found in the oat fractions were 5-CH(3)-H(4)folate, 5-HCO-H(4)folate,
      and 5,10-CH(+)-H(4)folate. The UPLC results more closely matched the
      microbiological results compared to those that are usually achieved with HPLC
      methods. This study illustrates that oats and, especially, by-products of milling
      are good sources of folate.

PMID- 22953944
TI  - Pancreatic islet proteome profile in Zucker fatty rats chronically treated with a
      grape seed procyanidin extract.
AB  - Grape seed procyanidin extract (GSPE) has been reported to modify glucose
      metabolism and beta-cell functionality through its lipid-lowering effects in a
      diet-induced obesity model. The objective of the present study was to evaluate
      the effects of chronically administrated GSPE on the proteomic profile of
      pancreatic islets from Zucker fatty (ZF) rats. An isobaric tag for relative and
      absolute quantitation (iTRAQ) experiment was conducted and 31 proteins were found
      to be differentially expressed in ZF rats treated with GSPE compared to untreated
      ZF rats. Of these proteins, five subcategories of biological processes emerged:
      hexose metabolic processes, response to hormone stimulus, apoptosis and cell
      death, translation and protein folding, and macromolecular complex assembly. Gene
      expression analysis supported the role of the first three biological processes,
      concluding that GSPE limits insulin synthesis and secretion and modulates factors
      involved in apoptosis, but these molecular changes are not sufficient to
      counteract the genetic background of the Zucker model at a physiological level.

PMID- 22953945
TI  - NMR-based metabolic profiling and in vitro antioxidant and hepatotoxic assessment
      of partially purified fractions from Golden germander (Teucrium polium L.)
      methanolic extract.
AB  - Golden germander (Teucrium polium L.) is a Mediterranean shrub of the Labiatae
      family, used in traditional medicine for its diuretic, antipyretic, diaphoretic,
      antispasmodic, tonic, anti-inflammatory, antihypertensive, anorexic, analgesic,
      antibacterial and antidiabetic effects. Like other plants of the Teucrium genus,
      it was widely popular because of its hypoglycemic and hypolipidemic properties
      but various cases of T. polium-induced hepatitis have been reported. neo
      Clerodane diterpenoids, considered chemotaxonomic markers for the Teucrium genus,
      are believed to be responsible for the observed hepatotoxicity. The plant also
      produces flavonoids and phenylethanoid glycosides to which the antioxidant and
      cytoprotective therapeutic properties of its preparations can be traced back. In
      order to establish a herbal formula that preserves the plant beneficial
      properties, T. polium leaf drug has been subjected to a bio-guided fractionation.
      The different phytocomplexes obtained were analyzed by means of an extensive
      antioxidant screening and hepatotoxicity evaluation against HepG2, a human
      hepatoblastoma cell line. The cytotoxicity of the fractions was also evaluated
      against HeLa and A549 cell lines. In order to identify the substances responsible
      for the bioactivities, NMR-based metabolic profiling techniques of all the
      phytocomplexes were performed. Data obtained highlighted the possibility of
      preparing strong antioxidant extracts, useful as food additives, such as MeOH-2,
      and MeOH-3, completely devoid of hepatotoxic components.

PMID- 22953946
TI  - Wholeness and primary and secondary food structure effects on in vitro digestion
      patterns determine nutritionally distinct carbohydrate fractions in cereal foods.
AB  - Starchy foods of differing structure, including bakery products, breakfast
      cereals, pastas, and pulses were digested in vitro. Bakery products and processed
      breakfast cereals with little resilient structure yielded large amounts of
      rapidly available carbohydrate (RAC), less slowly digested starch (SDS) and
      little inaccessible digestible starch (IDS) (70:22:8%). Partially processed
      grains, such as rolled oats contained an increased proportion of SDS (55:38:7%).
      Pastas, being dense starch structures digested more gradually to completion by
      superficial erosion, yielding approximately equal proportions of RAC and SDS but
      little IDS (43:52:4%). Pulses, which retained their cellular morphology, digested
      more linearly yielding a lower proportion of RAC, a larger proportion of SDS and
      more IDS (9:69:22%). Preservation of native "primary" structure, and use of
      processing to create "secondary" structure, are both means by which wholeness, in
      the sense of intactness, can be used to influence carbohydrate digestion to make
      foods of lower glycaemic impact.

PMID- 22953947
TI  - Structure and characteristics of acid and pepsin-solubilized collagens from the
      skin of cobia (Rachycentron canadum).
AB  - Acid-solubilized collagen (ASC) and pepsin-solubilized collagen (PSC) were
      extracted from the skin of cobia (Rachycentron canadum). The yields of ASC and
      PSC were 35.5% and 12.3%, respectively. Based on the protein patterns and
      carboxymethyl-cellulose chromatography, ASC and PSC were composed of
      alpha1alpha2alpha3 heterotrimers and were characterised as type I collagen with
      no disulfide bond. Their amounts of imino acids were 203 and 191 residues per
      1000 residues, respectively. LC-MS/MS analysis demonstrated the high sequences
      similarities of ASC and PSC. Fourier transform infrared spectroscopy spectra
      showed that the amide I, II and III peaks of PSC were obtained at a lower wave
      number compared with ASC. The thermal denaturation temperatures of ASC and PSC,
      as measured by viscometry, were 34.62 and 33.97 degrees C, respectively. The
      transition temperatures (T(max)) were 38.17 and 36.03 degrees C, respectively, as
      determined by differential scanning calorimetry (DSC). Both collagens were
      soluble at acidic pH and below 2% (w/v) NaCl concentration.

PMID- 22953948
TI  - Riboflavin and lumichrome in Dalmatian sage honey and other unifloral honeys
      determined by LC-DAD technique.
AB  - Riboflavin (vitamin B(2)) and its metabolite lumichrome were quantified in 117
      samples from 11 unifloral honeys types (Arbutus unedo L., Asphodelus microcarpus
      Salzm. et Viv., Citrus spp., Eucalyptus spp., Hedysarum coronarium L., Castanea
      sativa L. honeydew, Mentha spp., Paliurus spina-christi., Salix spp., Salvia
      officinalis L., Satureja spp.). The quantification of these two compounds was
      performed by LC-DAD method which does not require sample purification. The
      proposed method in our study has low limits of detection and quantification, very
      good linearity in a large concentration range and very good precision. It allows
      simultaneous determination of 5-hydroxymethylfurfural (HMF) and known chemical
      biomarkers of unifloral honeys such as abscisic acid diastereomers, homogentisic
      acid, methyl syringate and kynurenic acid. No statistical correlation was
      observed between riboflavin and lumichrome content. Although, the concentration
      of vitamin B(2) in honey may be too low (<6.1mg/kg) to generate interest in the
      field of nutrition, the presence of its main metabolite lumichrome may be useful
      to determine the botanical origin of certain unifloral honeys. In fact, the
      analysis of 11 unifloral honey types showed that Dalmatian sage (S. officinalis
      L.) honey is characterised by unusual high levels of lumichrome (20.2+/
      2.6mg/kg). The botanical origin of lumichrome from sage flower was assessed by
      analysing bee-stomach extracts. Other analytical parameters, such as total
      phenols, antioxidant and antiradical activities, HMF and diastase activity were
      studied in Dalmatian sage honey.

PMID- 22953949
TI  - Water at room temperature as a solvent for the extraction of apple pomace
      phenolic compounds.
AB  - A fractionation method was used to extract phenolic compounds from apple pomace
      (AP) involving a first extraction with water and subsequent extractions of the
      same residue with two different organic solvents. The water extracts obtained
      contained high amounts of phenolic compounds with high antioxidant capacity.
      However, the second and third extractions of the same residue still extracted
      considerable amounts of remaining phenolic compounds, both with significant
      antioxidant capacities. Liquid chromatography-electrospray ionisation mass
      spectrometry (LC-ESI/MS) studies showed water to be a good solvent to extract
      hydroxycinnamic acids, flavonols, flavanols, dihydrochalcones and flavones
      present in the AP. However, water was not the ideal solvent to extract the
      quercetin glycosides.

PMID- 22953950
TI  - o-Quinone involvement in the prooxidant tendency of a mixture of quercetin and
      caffeic acid.
AB  - The oxidation products of a previously tested prooxidant mixture of quercetin (Q)
      and caffeic acid (CA) at 1:2 ratio were analysed by LC-MS. The UV-Vis and MS
      spectra of three chromatographic peaks eluting at t(R)=9.11min, t(R)=14.36min and
      t(R)=30.30min were studied further. The structures of the tentatively identified
      compounds indicate polymeric molecules. A pentamer formed by 3 units of quercetin
      and 2 units of caffeic acid was attributed in the case of peaks t(R)=9.11min and
      t(R)=14.36min. The quercetin quinone (QQ) - a polymerization intermediate - is a
      fragment of the compound identified in the MS spectrum with the m/z=323 coming
      from Q o-quinone m/z=300 plus 23 from Na(+). According to the UV-Vis spectrum, we
      suggest a different intermolecular arrangement which gives a more extended e
      delocalisation. At t(R)=30.30min, the spectra helped us to tentatively identify
      this oxidation product as being a polymer of 4 CA units and 1 QQ.

PMID- 22953951
TI  - Biogenic amine formation and bacterial contribution in Natto products.
AB  - Twenty-one Natto products currently distributed in Korea were analysed for
      biogenic amine contents and tested to determine physicochemical and bacterial
      contributions to biogenic amine formation. Among them, nine products (about 43%)
      had beta-phenylethylamine or tyramine contents greater than the toxic dose
      (30mg/kg and 100mg/kg, respectively) of each amine, although no products showed
      total amounts of biogenic amines above the harmful level (1000mg/kg), which
      indicates that the amounts of biogenic amines in some Natto products are not
      within the safe level for human health. From four different Natto products, that
      contained noticeable levels of beta-phenylethylamine and tyramine, 80 bacterial
      strains were isolated. All the strains were identified to be Bacillus subtilis
      and highly capable of producing beta-phenylethylamine and tyramine. Therefore, it
      seems likely that the remarkable contents of beta-phenylethylamine and tyramine
      in Natto predominantly resulted from the strains highly capable of producing
      those amines present in the food.

PMID- 22953952
TI  - Is lowering reducing sugars concentration in French fries an effective measure to
      reduce acrylamide concentration in food service establishments?
AB  - The objective of this study was to obtain insight into the actual effectiveness
      of lowering reducing sugars concentration in par-fried potato strips on the
      concentration and variation of acrylamide in French fries prepared in real-life
      situations in food service establishments. Acrylamide, frying time, frying
      temperature, and reducing sugars were measured and characteristics of fryers were
      recorded. Data showed that the use of par-fried potato strips with lower
      concentrations of reducing sugars than the commonly used potato strips was an
      effective measure to reduce acrylamide concentrations in French fries prepared
      under standardised frying conditions. However, there was still large variation in
      the acrylamide concentrations in French fries, although the variation in reducing
      sugars concentrations in low and normal types of par-fried potato strips was very
      small and the frying conditions were similar. Factors that could affect the
      temperature-time profile of frying oil were discussed, such as setting a lower
      frying temperature at the end than at the start of frying, product/oil ratio and
      thawing practice. These need to be controlled in daily practice to reduce
      variation in acrylamide.

PMID- 22953953
TI  - Effects of pH and ionic strength of NaCl on the stability of diacetyl and (-)
      alpha-pinene in oil-in-water emulsions formed with food-grade emulsifiers.
AB  - The aim of the present study was to assess the influence of pH (3, 7 and 9) as
      well as ionic strength of NaCl (0mmol/l, 100mmol/l, 200mmol/l and 400mmol/l) on
      the retention and release characteristics of diacetyl and (-)-alpha-pinene in oil
      in-water (o/w) emulsions prepared with dried egg yolk (DEY) or starch sodium
      octenylsuccinate (SOE). Increase of pH from 3 to 9 progressively enhanced
      retention of diacetyl in emulsions prepared with both DEY and SOE. Whereas, in
      samples flavoured with (-)-alpha-pinene, the highest and lowest retention time
      courses were detected at pH 9 and pH 7 as well as pH 7 and pH 3 regarding
      emulsions prepared with DEY as well as SOE, respectively. With increasing salt
      concentration, the retention of diacetyl was decreased, irrespectively of the
      applied emulsifier type, whereas generally opposite effects were observed in the
      case of (-)-alpha-pinene. The parameters of release characteristics i.e., release
      rate constants (k) and release mechanism factors (n), were calculated using
      Avrami's equation. ANOVA revealed significant effects (p<0.001) of pH and NaCl
      concentration on k parameters, whereas relationship between applied environmental
      conditions and n factors was dependent on hydrophobicity of the odourant. Sensory
      evaluation revealed higher correlation values between odour intensity and aroma
      compound concentration in emulsions aromatized with (-)-alpha-pinene than with
      diacetyl.

PMID- 22953954
TI  - Antimutagenic and antioxidant activity of Lisosan G in Saccharomyces cerevisiae.
AB  - In the present study the antimutagenic and antioxidant effects of a powder of
      grain (Lisosan G) in yeast Saccharomyces cerevisiae were studied. Results showed
      that Lisosan G treatment decreased significantly the intracellular ROS
      concentration and mutagenesis induced by hydrogen peroxide in S. cerevisiae D7
      strain. The effect of Lisosan G was then evaluated by using superoxide dismutase
      (SOD) proficient and deficient strains of S. cerevisiae. Lisosan G showed
      protective activity in sod1Delta and sod2Delta mutant strains, indicating an in
      vivo antioxidant effect. A high radical scavenging activity of Lisosan G was also
      demonstrated in vitro using the oxygen radical absorbance capacity (ORAC) assay.
      The obtained results showed a protective effect of Lisosan G in yeast cells,
      indicating that its antioxidant capacity contributes to its antimutagenic action.

PMID- 22953955
TI  - Effect of the production method on the properties of RS3/RS4 type resistant
      starch. Part 2. Effect of a degree of substitution on the selected properties of
      acetylated retrograded starch.
AB  - Resistant starch displays health-promoting properties. Starch preparations
      produced through acetylation of retrograded starch may be applied as a food
      additive. Apart from prebiotic properties, they may as well model the texture of
      a food product. The objective of this study was to determine the effect of
      retrogradation and acetylation conditions on properties of the produced RS3/4
      type resistant starch. Native potato starch was used to produce starch pastes (1,
      4, 10, 18 or 30g/100g), that were frozen, defrosted and dried. The resultant
      preparations of retrograded starch were acetylated with various doses of an
      acetic acid anhydride (3.25, 6.5, 13.0, 26.0 or 52.0ml/100g). The acetylated
      preparations of retrograded starch were characterised by increasing solubility in
      water and swelling power as well as a lower amylose content along with an
      increasing degree of their substitution with residues of acetic acid.
      Dependencies of: pasting temperatures, viscosity of the prepared pastes, and
      resistance of acetylated starch to the action of amyloglucosidase on the degree
      of substitution with acetic acid residues were described with a second degree
      polynomial function. The extent and range of changes were found to depend on the
      concentration of paste used to produce a retrograded starch preparation. The
      maximum resistance of RS3/4 preparations to the action of amyloglucosidase ranged
      from 28.7 to 45.9g/100g.

PMID- 22953956
TI  - Searching ingredients polluted by polycyclic aromatic hydrocarbons in feeds due
      to atmospheric or pyrolytic sources.
AB  - The primary aim of the proposed work is to propose the potential sources of
      pollution by polycyclic aromatic hydrocarbons (PAHs) in feeds and ingredients. To
      reach this propose the development of a simple, fast, quantitative and economic
      method for determining PAHs using liquid-liquid extraction (LLE), clean-up and
      detection by liquid chromatography with fluorescence detection (LC-FD) in
      polluting feeds and ingredients was developed. The overall method quantification
      limits range from 0.020 to 4.0MUg/kg and analyte recoveries are between 70% and
      105% with relative standard deviations (RSD) lower than 20%. Molecular patterns
      of PAHs were used to study their distribution in the selected samples by cluster
      analysis, separating them in two groups: contaminated by atmospheric or pyrolytic
      sources. In order to find a relationship between the nutritional composition
      (protein, fibre, ash and fat content), and the hypothetical toxicity of selected
      feeds, a partial least squared (PLS) analysis was used, showing that fibre was a
      major contributor. Moreover, the complete data set of 27 feed samples and 25 feed
      ingredients x 13 PAH concentrations were analysed by PCA to find out what
      ingredients were controlling PAH pollution.

PMID- 22953957
TI  - Proteomic changes involved in tenderization of bovine Longissimus dorsi muscle
      during prolonged ageing.
AB  - To study proteomic changes involved in tenderization of bovine Longissimus dorsi
      four Charolaise heifers and four Charolaise bull's muscles were sampled at
      slaughter after early and long ageing (2-4 degrees C for 12 and 26days
      respectively). Descriptive sensory evaluation of samples were performed and their
      tenderness evaluated by Warner-Bratzler shear force test. Protein composition of
      fresh muscle and of meat aged was analysed by cartesian and polar 2-D
      electrophoresis. Student's t-test and Ranking-PCA analyses were performed to
      detect proteomic modulation, and the selected protein spots were identified by
      nano-HPLC-Chip MS/MS. This research has demonstrated that there are no
      differences between proteomic patterns of male and females Longissimus dorsi
      muscle, and that the extension of ageing beyond 12days, did not brings any
      concrete advantage in terms of sensory quality. Furthermore, the data presented
      here demonstrated that meat maturation caused changes of the abundance of
      proteins involved in metabolic, structural, and stress related processes.

PMID- 22953958
TI  - Free radical scavenging activity of morin 2'-O(-) phenoxide anion.
AB  - Due to intramolecular H-atom transfer, deprotonation of the most acidic 3-OH
      group of morin yields 2'-O(-) phenoxide anion. The reaction enthalpies related to
      mechanisms of free radical scavenging activity of this dominant species at a
      physiological pH of 7.4 were calculated by PM6 and DFT methods in gas-phase,
      water, benzene and DMSO. Results indicate the 4'-OH group of 2'-O(-) phenoxide
      anion is the active site for radical inactivation. The thermodynamically favoured
      mechanism depends on the polarity of the reaction media: in polar solvents (water
      and DMSO), the sequential proton loss electron transfer (SPLET) mechanism is
      preferred while in non-polar benzene (and in gas-phase), the hydrogen atom
      transfer (HAT) mechanism is responsible for the free radical scavenging activity
      of the morin phenoxide anion. Results show that the fast, semiempirical PM6
      method fairly mimics more accurate, though time-consuming DFT methodologies.

PMID- 22953959
TI  - Anti-diabetic activity peptides from albumin against alpha-glucosidase and alpha
      amylase.
AB  - The objectives of this study were to identify novel peptides from albumin, and to
      evaluate and validate the anti-diabetic activity of peptides against alpha
      glucosidase and alpha-amylase. In the research, albumin hydrolysate was purified
      and identified, tandem MS was adapted to characterise the amino acid sequences of
      peptides from the hydrolysate. In addition, anti-diabetic effects of the peptides
      with alpha-glucosidase and alpha-amylase inhibitory activity have been performed.
      The present work found eight novel peptides from albumin. Results also suggested
      that peptide KLPGF had alpha-glucosidase inhibitory activity with an IC(50) of
      59.5+/-5.7MUmoll(-1) and alpha-amylase inhibitory activity with an IC(50) of
      120.0+/-4.0MUmoll(-1). In conclusion, the results revealed that the peptide KLPGF
      was a potential anti-diabetic inhibitor.

PMID- 22953960
TI  - Chemical and antifungal investigations of six Lippia species (Verbenaceae) from
      Brazil.
AB  - The Lippia genus is used in ethnobotany as food, beverages, seasoning and
      antiseptic remedies, among others. The chemical compositions of fifteen extracts
      of six Lippia species were investigated comparatively by HPLC-PDA. To avoid data
      replication of previous works on this genus, Lippia lupulina Cham. root ethanol
      extract was selected for isolation procedures based on Principal Component
      Analyses (PCA) of such data. Seven compounds previously unreported in this genus
      were isolated from this extract (a triterpene, two furanonaphtoquinones, a
      furanochromone, an isoflavone, a stilbene and an iridoid). The activities of
      extracts, fractions and pure compounds towards Candida albicans, Candida krusei,
      Candida parapsilosis and Cryptococcus neoformans were investigated. Two fractions
      from the extract of Lippia salviaefolia leaves showed marked inhibition of fungal
      growth, in addition to verbascoside and asebogenin, which showed MICs lower than
      15.6MUg/ml and may be promising leads for the development of new antifungal
      agents, especially against C. neoformans.

PMID- 22953961
TI  - Crude caffeine reduces memory impairment and amyloid beta(1-42) levels in an
      Alzheimer's mouse model.
AB  - Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with
      the abnormal accumulations of amyloid beta (Abeta) peptide and oxidative stress
      in the brain, is the most common form of dementia among the elderly. Crude
      caffeine (CC), a major by-product of the decaffeination of coffee, has potent
      hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we
      showed that CC and pure caffeine intake had beneficial effects in a mouse model
      of AD. Administration of CC or pure caffeine for 2months partially prevented
      memory impairment in AD mice, with CC having greater effects than pure caffeine.
      Furthermore, consumption of CC, but not pure caffeine, reduced the Abeta(1-42)
      levels and the number of amyloid plaques in the hippocampus. Moreover, CC and
      caffeine protected primary neurons from Abeta-induced cell death and suppressed
      Abeta-induced caspase-3 activity. Our data indicate that CC may contain
      prophylactic agents against the cell death and the memory impairment in AD.

PMID- 22953962
TI  - Development of a novel micro-assay for evaluation of peroxyl radical scavenger
      capacity: application to carotenoids and structure-activity relationship.
AB  - A micro-assay was developed and validated, using a microplate reader in 96-well
      format, C(11)-BODIPY(581/591) as fluorescent probe and AIBN as ROO() generator.
      The structure-activity relationship was established for 15 carotenoid standards,
      indicating that the opening of the beta-ionone ring and the increase of
      chromophore extension in the carotenoid structure were the major factors leading
      to the increase of ROO() scavenging capacity. The values for ROO() scavenging
      capacity were calculated using alpha-tocopherol as reference compound. Among the
      studied carotenoids, all-trans-lycopene was the most efficient ROO() scavenger
      (8.67+/-0.74) followed by all-trans-astaxanthin (6.50+/-0.62). All the
      carotenoids showed to be more effective ROO() scavengers than alpha-tocopherol
      and some hydrophilic compounds. Finally, the method was successfully applied to
      assay the ROO() scavenging capacity of carotenoid extracts from two Amazonian
      fruits, peach palm (7.83+/-0.21) and mamey (6.90+/-0.44).

PMID- 22953963
TI  - Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway
      in HL-60 human promyelocytic leukaemia.
AB  - The present study was designed to evaluate the molecular mechanisms of the action
      of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60
      human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60
      cells in a dose- and time-dependent manner accompanied by the induction of
      apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The
      results showed that ACAN-induced the phosphorylation of members of the mitogen
      activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK
      (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK
      inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell
      viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no
      effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose
      polymerase (PARP), and decreased the level of Bcl-xL, but these effects were
      inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may
      have cancer chemopreventive and therapeutic potential, due to its ability to
      activate the p38 MAPK-mediated signalling pathways.

PMID- 22953964
TI  - Peer review: can we do better?

PMID- 22953965
TI  - Re: Reliability of subjective, linear, ratio, and area cephalometric measurements
      in assessing adenoid hypertrophy among different age groups. By Marcelo Quiroga
      Souki, Bernardo Quiroga Souki, Leticia Paiva Franco, Helena Maria Goncalves
      Becker and Eustaquio Afonso Araujo. ANGLE ORTHOD. 2012 E-Pub, doi: 
      http://dx.doi.org/10.2319/010612-13.1.

PMID- 22953967
TI  - Re: Root resorption diagnosed with cone beam computed tomography after 6 months
      of orthodontic treatment with fixed appliance and the relation to risk factors.
      Angle Orthod. 2012;82:196-201). By Dimitrios Makedonas, Henrik Lund, Kerstin
      Grondahl, Ken Hansen.

PMID- 22953970
TI  - Intravenous anesthetic propofol suppresses leukotriene production in murine
      dendritic cells.
AB  - Leukotrienes, divided into cysteinyl leukotrienes (CysLTs), which are important
      mediators of asthmatic responses, and leukotriene B4 (LTB4), a chemotactic and
      chemokinetic agent for leukocytes, are potent lipid mediators generated from
      arachidonic acid by 5-lipoxygenase (5-LO). Leukotrienes are also considered to
      have immunoregulatory and pro-inflammatory actions. Propofol is an intravenous
      anesthetic widely used for anesthesia and sedation that is alleged to possess
      anti-inflammatory properties. The present study examined the effect of propofol
      on leukotriene production by dendritic cells (DC). In murine bone marrow-derived
      DC, propofol significantly suppressed CysLT and LTB4 production after short-term
      stimulation with zymosan. The protein levels of cytosolic phospholipase A2 and 5
      LO, or arachidonic acid release from plasma membranes, were not affected by the
      presence of propofol. Although zymosan treatment induced or enhanced the
      phosphorylation of ERK1/2, p-38 MAPK, and JNK, which presumably up-regulates the
      activity of 5-LO, the presence of propofol had no additional effect on the
      phosphorylation status of any of these MAPKs. Similarly, zymosan significantly
      increased the concentration of intracellular calcium, which is the most crucial
      activator of 5-LO, but no additional concentration changes were observed with the
      addition of propofol. Lastly, in an in-vitro cell-free ferrous oxidation-xylenol
      orange assay, propofol significantly inhibited the 5-LO activity of purified
      human recombinant 5-LO enzyme with an IC50 of ~7.5 uM. Thus, propofol's
      inhibition of 5-LO is not likely restricted to the circumstances surrounding the
      production of leukotrienes from DC, but applicable to other types of immune and
      non-immune cells that produce leukotrienes. The 5-LO-inhibiting activity of
      propofol may, at least in part, contribute to the well-known anti-inflammatory
      activity of propofol. 

PMID- 22953971
TI  - Polylactide-based bionanocomposites: a promising class of hybrid materials.
AB  - Polylactide (PLA) is the oldest and potentially one of the most interesting and
      useful biodegradable man-made polymers because of its renewable origin,
      controlled synthesis, good mechanical properties, and inherent biocompatibility.
      The blending of PLA with functional nanoparticles can yield a new class of hybrid
      materials, commonly known as bionanocomposites, where 1-5% nanoparticles by
      volume are molecularly dispersed within the PLA matrix. The dispersed
      nanoparticles with their large surface areas and low percolation thresholds both
      can improve the properties significantly in comparison with neat PLA and can
      introduce new value-added properties. Recently, researchers have made
      extraordinary progress in the practical processing and development of products
      from PLA bionanocomposites. The variation of the nanofillers with different
      functionalities can lead to many bionanocomposite applications including
      environmentally friendly packaging, materials for construction, automobiles, and
      tissue regeneration, and load-bearing scaffolds for bone reconstruction. This
      Account focuses on these recent research efforts, processing techniques, and key
      research challenges in the development of PLA-based bionanocomposites for use in
      applications from green plastics to biomedical applications. Growing concerns
      over environmental issues and high demand for advanced polymeric materials with
      balanced properties have led to the development of bionanocomposites of PLA and
      natural origin fillers, such as nanoclays. The combination of nanoclays with the
      PLA matrix allows us to develop green nanocomposites that possess several
      superior properties. For example, adding ~5 vol % clay to PLA improved the
      storage modulus, tensile strength, break elongation, crystallization rate, and
      other mechanical properties. More importantly, the addition of clay decreases the
      gas and water vapor permeation, increases the heat distortion temperature and
      scratch resistance, and controls the biodegradation of the PLA matrix. In
      biomedicine, researchers have employed the design rules found in nature to
      fabricate PLA-based bionanocomposites. The incorporation of functional
      nanoparticles in the PLA matrix has improved the physical properties and changed
      the surface characteristics of the matrix that are important for tissue
      engineering and artificial bone reconstruction, such as its thermal and
      electrical conductivity, surface roughness, and wettability. Finally, of the
      introduction of bionanocomposite biocompatible surfaces on drugs, such as
      antibiotics, could produce delivery systems that act locally.

PMID- 22953972
TI  - Heparin can liberate high molecular weight DNA from secondary necrotic cells.
AB  - The borderline between necrosis and apoptosis is indistinct, but that between
      types of cell death is important because necrosis may lead to local inflammation,
      whereas apoptosis usually does not. In certain autoimmune disorders, inhibition
      of cell death is crucial, since macromolecules released from the dead cells may
      accelerate the autoimmune processes. We have used various cell death inhibitors
      to block cell death induced by 4HPR [N-(4-hydroxyphenil)-retinamide] the BL41 and
      U937 cell lines. VD-FMK, a general caspase inhibitor, inhibited DNA fragmentation
      induced by 4HPR, but not PI (propidium iodide) uptake and necrosis. Interestingly
      heparin, a serine-protease inhibitor, lowered the PI fluorescence of the dead
      cell population and increased the sub-G1 population as measured by flow
      cytometry. Regarding these changes, we found that heparin failed to increase DNA
      fragmentation, but merely liberated high molecular mass DNA fragments from dead
      cells. The exact mechanism is unclear, but heparin during secondary necrosis
      might enter the cells, bind RNPs (ribonucleoproteins), and pull them out with the
      attached DNA, where they would be sensitive to enzymatic degradation. Thus, the
      results suggest that heparin treatment helps in the clearance of cell debris and
      decreases the immunogenity of secondary necrotic cells.

PMID- 22953973
TI  - Genetic parameter estimates and principal component analysis of breeding values
      of reproduction and growth traits in female Canchim cattle.
AB  - Phenotypic data from female Canchim beef cattle were used to obtain estimates of
      genetic parameters for reproduction and growth traits using a linear animal mixed
      model. In addition, relationships among animal estimated breeding values (EBVs)
      for these traits were explored using principal component analysis. The traits
      studied in female Canchim cattle were age at first calving (AFC), age at second
      calving (ASC), calving interval (CI), and bodyweight at 420 days of age (BW420).
      The heritability estimates for AFC, ASC, CI and BW420 were 0.03+/-0.01, 0.07+/
      0.01, 0.06+/-0.02, and 0.24+/-0.02, respectively. The genetic correlations for
      AFC with ASC, AFC with CI, AFC with BW420, ASC with CI, ASC with BW420, and CI
      with BW420 were 0.87+/-0.07, 0.23+/-0.02, -0.15+/-0.01, 0.67+/-0.13, -0.07+/
      0.13, and 0.02+/-0.14, respectively. Standardised EBVs for AFC, ASC and CI
      exhibited a high association with the first principal component, whereas the
      standardised EBV for BW420 was closely associated with the second principal
      component. The heritability estimates for AFC, ASC and CI suggest that these
      traits would respond slowly to selection. However, selection response could be
      enhanced by constructing selection indices based on the principal components.

PMID- 22953974
TI  - Office-based management of pediatric and adolescent concussion.

PMID- 22953975
TI  - Importance of 'return-to-learn' in pediatric and adolescent concussion.

PMID- 22953976
TI  - Rehabilitation strategies for prolonged recovery in pediatric and adolescent
      concussion.

PMID- 22953978
TI  - A daily dose of recommended exercise.

PMID- 22953979
TI  - A 13-year-old girl with nocturnal chest pain.

PMID- 22953980
TI  - Put some 'teeth' into your pediatric preventive counseling.

PMID- 22953981
TI  - A 6-year-old boy with a nodule on his hand.

PMID- 22953982
TI  - Concussion: latest diagnosis and treatment recommendations.

PMID- 22953983
TI  - Computerized neurocognitive testing in the medical evaluation of sports
      concussion.

PMID- 22953984
TI  - Concussion pathophysiology: rationale for physical and cognitive rest.

PMID- 22953985
TI  - A conversation with Paula Duncan, MD. Interviewed by Stanford T. Shulman.

PMID- 22953986
TI  - Mechanical transition from alpha-helical coiled coils to beta-sheets in
      fibrin(ogen).
AB  - We characterized the alpha-to-beta transition in alpha-helical coiled-coil
      connectors of the human fibrin(ogen) molecule using biomolecular simulations of
      their forced elongation and theoretical modeling. The force (F)-extension (X)
      profiles show three distinct regimes: (1) the elastic regime, in which the coiled
      coils act as entropic springs (F < 100-125 pN; X < 7-8 nm); (2) the constant
      force plastic regime, characterized by a force-plateau (F ~ 150 pN; X ~ 10-35
      nm); and (3) the nonlinear regime (F > 175-200 pN; X > 40-50 nm). In the plastic
      regime, the three-stranded alpha-helices undergo a noncooperative phase
      transition to form parallel three-stranded beta-sheets. The critical extension of
      the alpha-helices is 0.25 nm, and the energy difference between the alpha-helices
      and beta-sheets is 4.9 kcal/mol per helical pitch. The soft alpha-to-beta phase
      transition in coiled coils might be a universal mechanism underlying mechanical
      properties of filamentous alpha-helical proteins.

PMID- 22953987
TI  - Conjugate of Pt(IV)-histone deacetylase inhibitor as a prodrug for cancer
      chemotherapy.
AB  - Platinum(IV) prodrug diaminedichlorodihydroxyplatinum (ACHP) conjugated with a
      histone deacetylase (HDAC) inhibitor valproic acid (VA), VAAP, exhibited strong
      synergistic cytotoxicity, about 50-100 times more cytotoxic than ACHP or its
      simple mixture with VA, against various human carcinoma cell lines. VAAP could be
      quickly absorbed in the cell membrane and diffused into the cytosol. VAAP loaded
      in polyethylene glycol-polycaprolactone micelles (PEG-PCL) was taken up via
      endocytosis. The cytosolic VAAP was intracellular reduced to Pt(II) and released
      VA eliciting a HDAC inhibitory effect and subsequently induced cell cycle arrest
      at the S phase in 24 h and cell apoptosis in a time-dependent manner. The in vivo
      antitumor experiment on A549-xenograft tumor model showed that VAAP dispersed in
      Tween 80 or loaded in PEG-PCL nanoparticles had long blood circulation times and
      thereby high accumulation in tumors and exerted a significant in vivo inhibitory
      effect on tumor growth with low systemic toxicity. Therefore, this novel
      conjugate is very promising for cancer chemotherapy.

PMID- 22953988
TI  - Reference values of impulse oscillometry and its utility in the diagnosis of
      asthma in young Korean children.
AB  - AIMS: The aims of this study were (1) to determine the reference values for
      impulse oscillometry (IOS) and (2) to apply them to the evaluation of asthma in
      the general population of young Korean children. METHODS: We performed a
      questionnaire survey and IOS measurements in 390 children aged 3-7 years in Seoul
      and Gyeonggi province, Korea, from July to August 2010. IOS measurements included
      respiratory resistance (Rrs) and respiratory reactance (Xrs) at 5, 10, 15, 20,
      25, and 35 Hz, respiratory impedance (Zrs), and resonance frequency (RF) before
      and 15 min after inhalation of 200 MUg salbutamol. To determine the reference
      values for IOS, 161 children defined as healthy controls were assessed. RESULTS:
      The IOS measurements were presented as means and standard deviations. The
      reference equations for IOS variables were determined by multiple linear
      regression analysis taking into account their height, weight, and age (R5 = 2.242
      - 0.008 * height (cm) - 0.005 * age (months), coefficients of determination
      (R(2)) = 0.213). Height had the greatest correlation with IOS variables, similar
      to previous studies. Positive airway obstruction was defined as R5 greater than
      the 95th percentile of predicted R5 from the reference equation. There was a
      higher percentage of children with positive airway obstruction in children with
      asthma than in healthy controls (27.3% vs. 6.2%). Multivariate logistic
      regression analysis indicated that positive airway obstruction was a significant
      risk factor for the diagnosis of asthma (adjusted odds ratio (aOR), 6.245; 95%
      confidence interval (CI), 2.270-17.175). CONCLUSION: This study provided
      reference values for IOS in young Korean children and applied the reference
      values to evaluate children with asthma. We suggest the 95th percentile of
      predicted R5 as a cut-off value for positive airway obstruction, which may
      increase the risk for diagnosis of asthma.

PMID- 22953990
TI  - Evidence for higher success rates and successful treatment earlier in Graves'
      disease with higher radioactive iodine doses.
AB  - BACKGROUND: Graves' disease is commonly treated with curative intent using
      radioactive iodine (RAI). While higher doses have been shown to increase success
      rates, more evidence is needed. Further, very few studies assess the time to
      treatment success without the need for antithyroid drugs after a single dose of
      RAI within the first year post-dose, despite earlier success being an important
      treatment objective. We aimed to evaluate the outcome of different RAI doses in
      terms of success rates and time to achieve this success (eu- or hypothyroidism).
      We hypothesized that higher doses would not only increase success rates, but
      bring about successful treatment earlier. METHODS: We retrospectively analyzed
      the medical records of all patients diagnosed with Graves' disease between 1994
      and 2009. Details of RAI treatment and outcomes thereof were documented. In our
      analysis, we divided the patients who received RAI treatment into three groups
      according to the dose received: I (<=15 mCi); II (16-20 mCi); III (>=21 mCi).
      RESULTS: There were 498 patients diagnosed with Graves' disease. However, 105
      were either lost to follow-up or still undergoing treatment. Of the remaining
      393, there were 258 who received RAI treatment. The average initial dose was
      21.42+/-6.5 mCi and overall success rate was 86%. Success rates were 74%, 85%,
      and 89% (p<0.05), while average time to successful treatment was 8.1, 4.6, and
      2.9 months, respectively (p<0.001), for groups I, II, and III. When 20 mCi was
      given empirically, 85% obtained successful treatment; most of these within 3
      months (mean 3.9; mode and median 3 months). CONCLUSIONS: This study provides
      additional evidence that success post-treatment correlates with administered dose
      and shows clearly, for the first time, that successful treatment is achieved
      earlier with higher doses. This knowledge is relevant to all clinicians managing
      Graves' disease as it can be taken into consideration when discussing treatment
      plans with patients.

PMID- 22953991
TI  - Lithium as an adjuvant in the postoperative ablation of remnant tissue in low
      risk thyroid carcinoma.
AB  - BACKGROUND: Thyroid remnant ablation (RA) with 30 mCi of radioactive iodine
      (131I) in patients thyroidectomized for treatment of low-risk differentiated
      thyroid carcinoma (DTC) has a success rate of 64% to 84%. Lithium increases the
      residence time of 131I in the thyroid tissue. The aim of this study was to
      determine if lithium treatment added to 30 mCi 131I would enhance the success
      rate of this treatment compared with 30 mCi 131I alone in patients who were
      thyroidectomized for treatment of low-risk DTC. METHODS: This was a randomized
      study with endpoint at one year. Sixty one consecutive patients were enrolled and
      randomized into two groups: group A (n=32) treated with 30 mCi 131I; group B
      (n=29) treated with 30 mCi 131I plus an oral dose of lithium 900 mg/day, for 7
      days. All patients were evaluated by whole body scan (WBS) with 123I and had
      serum TSH, thyroglobulin (Tg), and anti-Tg antibodies (TgAb) determined when they
      were hypothyroid on no thyroid hormone. Patients were reevaluated after one year
      with serum TSH, Tg, and TgAb determinations and WBS with 123I. The criteria for
      defining a successful outcome was a negative WBS and a serum Tg of <1. RESULTS:
      Group A was composed of 28 women and four men (ages 25-71 years) with 2 having
      follicular thyroid carcinoma (FTC), 22 having papillary thyroid carcinoma (PTC)
      of 1-4.5 cm, and 8 having micro PTCs (mPTC) of 0.3-0.8 cm. Group B was composed
      of 26 women and 3 men (ages 20-63 years) with 3 having FTC, 15 having PTC of 1.2
      3.5 cm, and 11 having mPTC of 0.2-0.8 cm. All patients had a history of a WBS
      after their post-therapeutic 131I dose that showed uptake in the cervical region.
      After one year, 22 patients from group A had a negative WBS (68.75%) and in group
      B, 27 patients had a negative WBS (93.1%). The successful rates for the follow-up
      WBS were significantly different (p=0.017). There were 19 patients in group A in
      whom the initial Tg was positive. Of these, 14 had a negative follow-up Tg
      (73.7%). Group B had 9 patients with a positive initial Tg and all of them had a
      negative follow-up Tg (100%). CONCLUSION: The addition of lithium to treatment
      with 30 mCi 131I in thyroidectomized patients with low-risk DTC improved the
      efficacy of thyroid RA and therefore might be a better alternative than using
      higher doses of 131I for remnant ablation in these patients.

PMID- 22953989
TI  - Towards more effective robotic gait training for stroke rehabilitation: a review.
AB  - BACKGROUND: Stroke is the most common cause of disability in the developed world
      and can severely degrade walking function. Robot-driven gait therapy can provide
      assistance to patients during training and offers a number of advantages over
      other forms of therapy. These potential benefits do not, however, seem to have
      been fully realised as of yet in clinical practice. OBJECTIVES: This review
      determines ways in which robot-driven gait technology could be improved in order
      to achieve better outcomes in gait rehabilitation. METHODS: The literature on
      gait impairments caused by stroke is reviewed, followed by research detailing the
      different pathways to recovery. The outcomes of clinical trials investigating
      robot-driven gait therapy are then examined. Finally, an analysis of the
      literature focused on the technical features of the robot-based devices is
      presented. This review thus combines both clinical and technical aspects in order
      to determine the routes by which robot-driven gait therapy could be further
      developed. CONCLUSIONS: Active subject participation in robot-driven gait therapy
      is vital to many of the potential recovery pathways and is therefore an important
      feature of gait training. Higher levels of subject participation and challenge
      could be promoted through designs with a high emphasis on robotic transparency
      and sufficient degrees of freedom to allow other aspects of gait such as balance
      to be incorporated.

PMID- 22953992
TI  - AMP-activated protein kinase upregulates glucose uptake in thyroid PCCL3 cells
      independent of thyrotropin.
AB  - BACKGROUND: Glucose is transported into cells by specific glucose transporter
      proteins (GLUTs) that are widely expressed in a tissue-specific manner. The
      mechanisms that regulate glucose uptake and metabolism in thyroid cells are
      poorly defined. Recently, our group showed that AMP-activated protein kinase
      (AMPK) plays a pivotal role in the rat thyroid gland, downregulating iodide
      uptake by thyroid cells even in the presence of its main stimulator thyrotropin
      (TSH). Since AMPK increases glucose uptake in different tissues, and taken into
      consideration that in pathophysiological conditions such as thyroid cancer a
      negative correlation between iodide and glucose uptake occurs, we hypothesized
      that AMPK might modulate glucose uptake in thyroid cells. METHODS: Rat follicular
      thyroid PCCL3 cells cultivated in Ham's F-12 supplemented with 5% calf serum and
      hormones were exposed to the AMPK pharmacological activator 5-aminoimidazole-4
      carboxamide ribonucleoside (AICAR) or AMPK antagonist compound C for 24 hours
      either in the presence or absence of TSH. Glucose uptake was assessed in vitro
      using 2-deoxy-D-[(3)H]glucose. RESULTS: AMPK activation by AICAR induced a
      significant increase in glucose uptake by PCCL3 cells, an effect that was
      completely reversed by the AMPK inhibitor compound C. Also, the AICAR mediated
      increase in glucose uptake was detected either in the presence or absence of TSH.
      The mechanism by which AICAR increases glucose uptake is related to higher levels
      of GLUT 1 protein content and hexokinase (HK) activity in thyroid cells.
      CONCLUSION: Our results show that AMPK activation significantly upregulates GLUT
      1 content and glucose uptake, and it also stimulates hexokinase activity, the
      first step of glycolysis.

PMID- 22953993
TI  - Mimicking the functional niche of adipose-derived stem cells for regenerative
      medicine.
AB  - INTRODUCTION: A stem cell (SC) niche is defined as the microenvironment in which
      the adult SC resides and includes surrounding cells, low oxygen content and
      growth factor gradients. Crosstalk between SCs and their niche provides signals
      that keep SCs quiescent, or modulates their activation. AREAS COVERED: This
      review discusses the characterization of niche conditions in the adipose-derived
      stem cell (ASC) in vivo environment, and introduces key signalling pathways and
      autocrine/paracrine regulators of ASCs. EXPERT OPINION: Control of in vivo niche
      factors (such as low oxygen content, generation of reactive oxygen species and
      activation of platelet-derived growth factor receptor signalling) should increase
      ASC yields synergistically and reduce production costs. Additionally, the
      preconditioning of ASCs with these niche factors prior to transplantation might
      enhance their regenerative potential. ASC niche is complex, and there are
      components of the niche that we may not yet understand. Therefore, future
      research needs to focus on identifying the key regulatory factors of the ASC
      niche in vivo, and developing a novel method to mimic these niche factors for in
      vitro manipulation.

PMID- 22953994
TI  - Does improved functional performance help to reduce urinary incontinence in
      institutionalized older women? A multicenter randomized clinical trial.
AB  - BACKGROUND: Urinary incontinence (UI) is a major problem in older women.
      Management is usually restricted to dealing with the consequences instead of
      treating underlying causes such as bladder dysfunction or reduced mobility.The
      aim of this multicenter randomized controlled trial was to compare a group-based
      behavioral exercise program to prevent or reduce UI, with usual care. The
      exercise program aimed to improve functional performance of pelvic floor muscle
      (PFM), bladder and physical performance of women living in homes for the elderly.
      METHODS: Twenty participating Dutch homes were matched and randomized into
      intervention or control homes using a random number generator. Homes recruited 6
      10 older women, with or without UI, with sufficient cognitive and physical
      function to participate in the program comprising behavioral aspects of
      continence and physical exercises to improve PFM, bladder and physical
      performance. The program consisted of a weekly group training session and
      homework exercises and ran for 6 months during which time the control group
      participants received care as usual. Primary outcome measures after 6 months were
      presence or absence of UI, frequency of episodes (measured by participants and
      caregivers (not blinded) using a 3-day bladder diary) and the Physical
      Performance Test (blinded). Linear and logistic regression analysis based on the
      Intention to Treat (ITT) principle using an imputed data set and per protocol
      analysis including all participants who completed the study and intervention
      (minimal attendance of 14 sessions). RESULTS: 102 participants were allocated to
      the program and 90 to care as usual. ITT analysis (n = 85 intervention, n = 70
      control) showed improvement of physical performance (intervention +8%; control 
      7%) and no differences on other primary and secondary outcome measures. Per
      protocol analysis (n = 51 intervention, n = 60 control) showed a reduction of
      participants with UI (intervention -40%; control -28%) and in frequency of
      episodes (intervention -51%; control -42%) in both groups; improvement of
      physical performance (intervention + 13%; control -4%) was related to
      participation in the exercise program. CONCLUSIONS: This study shows that
      improving physical performance is feasible in institutionalized older women by
      exercise. Observed reductions in UI were not related to the intervention.
      [Current Controlled Trials ISRCTN63368283].

PMID- 22953995
TI  - The work pattern of personal care workers in two Australian nursing homes: a time
      motion study.
AB  - BACKGROUND: The aim of the study is to describe the work pattern of personal care
      workers (PCWs) in nursing homes. This knowledge is important for staff
      performance appraisal, task allocation and scheduling. It will also support
      funding allocation based on activities. METHODS: A time-motion study was
      conducted in 2010 at two Australian nursing homes. The observation at Site 1 was
      between the hours of 7:00 and 14:00 or 15:00 for 14 days. One PCW was observed on
      each day. The observation at Site 2 was from 10:00 to 17:00 for 16 days. One PCW
      working on a morning shift and another one working on an afternoon shift were
      observed on each day. Fifty-eight work activities done by PCWs were grouped into
      eight categories. Activity time, frequency, duration and the switch between two
      consecutive activities were used as measurements to describe the work pattern.
      RESULTS: Personal care workers spent about 70.0% of their time on four types of
      activities consistently at both sites: direct care (30.7%), indirect care
      (17.6%), infection control (6.4%) and staff break (15.2%). Oral communication was
      the most frequently observed activity. It could occur independently or
      concurrently with other activities. At Site 2, PCWs spent significantly more time
      than their counterparts at Site 1 on oral communication (Site 1: 47.3% vs. Site
      2: 63.5%, P = 0.003), transit (Site 1: 3.4% vs. Site 2: 5.5%, P < 0.001) and
      others (Site 1: 0.5% vs. Site 2: 1.8%, P < 0.001). They spent less time on
      documentation (Site 1: 4.1% vs. Site 2: 2.3%, P < 0.001). More than two-thirds of
      the observed activities had a very short duration (1 minute or less). Personal
      care workers frequently switched within or between oral communication, direct and
      indirect care activities. CONCLUSIONS: At both nursing homes, direct care,
      indirect care, infection control and staff break occupied the major part of a
      PCW's work, however oral communication was the most time consuming activity.
      Personal care workers frequently switched between activities, suggesting that
      looking after the elderly in nursing homes is a busy and demanding job.

PMID- 22953996
TI  - Critical involvement of the E373-D434 region in the acid sensitivity of a NhaB
      type Na(+)/H(+) antiporter from Vibrio alginolyticus.
AB  - It has been well established that VaNhaB, a NhaB-type Na(+)/H(+) antiporter found
      in Vibrio alginolyticus, exhibits a striking acid sensitivity. However, the
      molecular basis of the pH-dependent regulatory mechanism of the antiport activity
      is yet to be investigated. In this study, we generated various chimeric proteins
      composed of VaNhaB and a pH insensitive ortholog found in Escherichia coli
      (EcNhaB) and analyzed the pH responses of their Na(+)/H(+) antiport activities to
      search for the key residues or domains that are involved in the pH sensitivity of
      VaNhaB. Our results revealed the significant importance of a stretch of amino
      acid residues within the loop 8-loop 9 regions (E373-D434) responsible for the
      acid sensitivity of VaNhaB, along with the possible involvement of other
      unidentified residues that are widely spread in the primary structure of VaNhaB.
      Moreover, we demonstrated that the E373-D434 region of VaNhaB was able to confer
      some degree of acid sensitivity on our pH insensitive chimeric antiporter that is
      mainly composed of EcNhaB except for seven amino acid substitutions at the N
      terminal end. This result strongly suggested the possibility that the E373-D434
      region is able to act, at least partially, as machinery that diminishes the
      activity of the NhaB-type antiporter at an acidic pH.

PMID- 22953997
TI  - Effect of chronic pretreatment of angiotensin-converting receptor blocker on no
      reflow phenomenon in patients with acute myocardial infarction undergoing
      percutaneous coronary intervention.
AB  - AIMS: Angiotensin receptor blockers (ARBs) exert favorable effects on the
      vascular system, which are not directly related to hypertension lowering
      function. The no-reflow phenomenon determines the prognosis in patients after
      acute myocardial infarction (AMI). Early ARB treatment has many beneficial
      effects on the prognosis after AMI. In this study, we tested the hypothesis that
      ARB treatment before admission would have beneficial effects on the development
      of the no-reflow phenomenon after infarction. METHODS: We investigated 276
      consecutive patients with AMI undergoing successful primary percutaneous coronary
      intervention (PCI). No-reflow was defined as thrombolysis in myocardial
      infarction (TIMI) flow grade <3, which was determined by the TIMI frame count
      method using angiographic images obtained just after PCI and stenting. RESULTS:
      Compared with patients without ARB treatment, patients with ARB had more
      frequently hypertension and ST resolution (P < 0.05), but no significant
      difference was found in the other clinical characteristics (age, sex,
      Hyperlipidaemia, Diabetes mellitus, etc) between the two groups. A total of 51
      patients receiving chronic ARB treatment before admission have lower incidence of
      the no-reflow phenomenon than those without chronic ARB treatment (8.7% and
      26.7%, P= 0.003). However, the incidence of the no-reflow phenomenon between the
      patients with and without hypertension had no significant difference.
      Multivariable logistic regression analysis revealed that ARB pretreatment was a
      significant predictor of the no-reflow phenomenon, whereas blood pressure was
      found to be insignificant. CONCLUSION: Chronic pretreatment of ARB is associated
      with the reduction of the no-reflow phenomenon in patients with reperfused AMI
      and could preserve microvascular integrity after AMI independent of blood
      pressure lowering, which may contribute to better functional recovery.

PMID- 22953998
TI  - Obligate larval inhibition of Ostertagia gruehneri in Rangifer tarandus? Causes
      and consequences in an Arctic system.
AB  - Larval inhibition is a common strategy of Trichostrongylidae nematodes that may
      increase survival of larvae during unfavourable periods and concentrate egg
      production when conditions are favourable for development and transmission. We
      investigated the propensity for larval inhibition in a population of Ostertagia
      gruehneri, the most common gastrointestinal Trichostrongylidae nematode of
      Rangifer tarandus. Initial experimental infections of 4 reindeer with O.
      gruehneri sourced from the Bathurst caribou herd in Arctic Canada suggested that
      the propensity for larval inhibition was 100%. In the summer of 2009 we infected
      12 additional reindeer with the F1 and F2 generations of O. gruehneri sourced
      from the previously infected reindeer to further investigate the propensity of
      larval inhibition. The reindeer were divided into 2 groups and half were infected
      before the summer solstice (17 June) and half were infected after the solstice
      (16 July). Reindeer did not shed eggs until March 2010, i.e. 8 and 9 months post
      infection. These results suggest obligate larval inhibition for at least 1
      population of O. gruehneri, a phenomenon that has not been conclusively shown for
      any other trichostrongylid species. Obligate inhibition is likely to be an
      adaptation to both the Arctic environment and to a migratory host and may
      influence the ability of O. gruehneri to adapt to climate change.

PMID- 22953999
TI  - Age and pancreaticoduodenctomy: is it really about mortality?

PMID- 22954000
TI  - Advanced age is a risk factor for post-operative complications and mortality
      after a pancreaticoduodenectomy: a meta-analysis and systematic review.
AB  - BACKGROUND: The aim of this meta-analysis was to analyse the outcomes of major
      pancreatic surgery among the elderly (>=75 and >=80 years of age). METHODS: A
      systematic literature search was conducted using Embase, MEDLINE, Cochrane and
      PubMed databases on all studies published between January 1990 and April 2012
      reporting peri-operative outcomes after a pancreaticoduodenectomy (PD) among the
      elderly. Primary end-points measured were peri-operative mortality and the
      incidence of post-operative complications. Secondary outcomes considered included
      the incidence of post-operative pancreatic fistula formation (POPF), delayed
      gastric emptying (DGE), wound infection, pneumonia, post-operative bleeding and
      length of hospital stay. RESULTS: Eleven trials were included comprising 5186
      patients; 7 studies comparing endpoints in patients aged >=75 years vs. younger
      populations and 4 studies comparing endpoints in patients aged >=80 years vs.
      younger populations. In both groups, there was a statistically significant
      increase in the incidence of mortality and post-operative pneumonia in the
      elderly population. The incidence of post-operative complications was also found
      to be statistically significant among patients >=80 years of age vs. their
      younger cohorts. CONCLUSIONS: There is an increased incidence of post-operative
      mortality and pneumonia after a PD among all elderly patients >=75 years of age,
      as well as an increased incidence of post-operative complications among patients
      >=80 years of age. Additional randomized control trials studying post-PD
      operative outcomes in elderly vs. younger patients with standardization of
      comorbidities is therefore necessary to confirm the conclusions presented here.

PMID- 22954001
TI  - Multimodality imaging of pancreatic ductal adenocarcinoma: a review of the
      literature.
AB  - BACKGROUND: Accurate pre-operative imaging in pancreatic cancer helps avoid
      unsuccessful surgical explorations and forewarns surgeons regarding aberrant
      anatomy. This review aimed to determine the role of current imaging modalities in
      the diagnosis and determination of resectability of pancreatic and peri-ampullary
      adenocarcinomas. METHODS: A systematic search of the scientific literature was
      carried out using EMBASE, PubMed/MEDLINE and the Cochrane Central Register of
      Controlled Trials for the years 1990 to 2011 to obtain access to all
      publications, especially randomized controlled trials, reporting on the
      diagnostic accuracy of ultrasonography, multi-detector computed tomography
      (MDCT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) or
      positron emission tomography (PET)-computed tomography (CT) and the evaluation of
      resectability of pancreatic and peri-ampullary adenocarcinomas. RESULTS: Based on
      66 articles analysed in the review, MDCT and MRI/MRCP have comparable sensitivity
      and specificity rates for diagnosis and staging of pancreatic cancers. EUS offers
      the best sensitivity and specificity rates for lesions <2 cm. Improved staging
      has been noted when PET-CT scans are added to pre-operative evaluation.
      CONCLUSIONS: MDCT with angiography or MRI/MRCP should constitute the first
      imaging modality in suspected pancreatic adenocarcinomas. EUS is recommended for
      assessing lesions not clearly detected, but suspected, on CT/MRI and in tumours
      considered 'borderline resectable' on MDCT to assess vascular involvement. PET-CT
      in locally advanced lesions will help rule out distant metastases.

PMID- 22954002
TI  - Torsion of the gallbladder: a systematic review.
AB  - BACKGROUND: Gallbladder torsion is a rare disease, predominantly affecting
      elderly women. It is an important differential in the acute surgical abdomen.
      METHODS: A total of 324 published case reports of torsion of the gallbladder were
      reviewed. Features in diagnostic imaging suggestive of torsion were reviewed and
      summarized. RESULTS: Gallbladder torsion is primarily a disease of elderly
      people; the median age at presentation is 77 years. It is more common amongst
      women, occurring at a female : male ratio of 4 : 1, although not in childhood,
      when it occurs at a male : female ratio of 2.5 : 1. CONCLUSIONS: Improved imaging
      techniques within the last 20 years have enabled the preoperative diagnosis of
      one quarter of patients with gallbladder torsion. With prompt surgical
      intervention, the condition has an excellent prognosis.

PMID- 22954003
TI  - A survey of the accuracy of interpretation of intraoperative cholangiograms.
AB  - OBJECTIVES: There are few data in the literature regarding the ability of
      surgical trainees and surgeons to correctly interpret intraoperative
      cholangiograms (IOCs) during laparoscopic cholecystectomy (LC). The aim of this
      study was to determine the accuracy of surgeons' interpretations of IOCs.
      METHODS: Fifteen IOCs, depicting normal, variants of normal and abnormal anatomy,
      were sent electronically in random sequence to 20 surgical trainees and 20
      consultant general surgeons. Information was also sought on the routine or
      selective use of IOC by respondents. RESULTS: The accuracy of IOC interpretation
      was poor. Only nine surgeons and nine trainees correctly interpreted the
      cholangiograms showing normal anatomy. Six consultant surgeons and five trainees
      correctly identified variants of normal anatomy on cholangiograms. Abnormal
      anatomy on cholangiograms was identified correctly by 18 consultant surgeons and
      19 trainees. Routine IOC was practised by seven consultants and six trainees.
      There was no significant difference between those who performed routine and
      selective IOC with respect to correct identification of normal, variant and
      abnormal anatomy. CONCLUSIONS: The present study shows that the accuracy of
      detection of both normal and variants of normal anatomy was poor in all grades of
      surgeon irrespective of a policy of routine or selective IOC. Improving
      operators' understanding of biliary anatomy may help to increase the diagnostic
      accuracy of IOC interpretation.

PMID- 22954005
TI  - Risk factors associated with delayed haemorrhage after pancreatic resection.
AB  - BACKGROUND: Delayed haemorrhage (DH) is a life-threatening complication of
      pancreatic resection (PR) and the mortality rate for DH is very high. However,
      the risk factors and prognostic factors associated with DH are rarely evaluated.
      METHODS: A pancreatic resection was performed on 457 patients. Delayed
      haemorrhage was defined as bleeding from the surgical site >= 5 days after PR.
      Risk factors for DH were assessed according to demographics and pathological and
      operative parameters. Prognostic factors after DH were evaluated for the shock
      index (heart rate/systolic blood pressure) and systemic inflammatory response
      syndrome (SIRS) scores. RESULTS: Of the 457 patients, 11 (2.4%) experienced DH
      after PR. Logistic regression analysis showed that age >60 years and a diagnosis
      of malignant disease were risk factors for DH. The shock index and SIRS scores at
      the onset of DH were significantly higher in patients who died as compared with
      those patients that survived (P < 0.05). DISCUSSION: PR-associated DH carries an
      increased risk for patients aged >60 years with malignant disease. Prognostic
      factors were a shock index score >= 0.7 and SIRS at the onset of DH.

PMID- 22954004
TI  - GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the
      bile duct.
AB  - BACKGROUND: Activating point mutations of GNAS at codon 201 have been detected in
      approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of
      the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs)
      morphologically resemble pancreatic IPMNs. This study sought to assess the
      mutational status of GNAS at codon 201 in IPNBs. METHODS: Thirty-four patients
      were included. DNA from microdissected IPNBs was subjected to a polymerase chain
      reaction and ligation method for the detection of GNAS mutations at codon 201 and
      of KRAS mutations at codon 12. Mutational status was compared with clinical and
      pathologic data. RESULTS: The IPNBs had a median diameter of 3.5 cm and were
      located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and
      extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms,
      n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade
      dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS
      codon 201 identified only one mutant sample in a multifocal intestinal subtype
      intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon
      12 mutation. CONCLUSIONS: GNAS codon 201 mutations are uncommon in IPNBs, by
      contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed
      to uncover the pathways involved in IPNB development.

PMID- 22954006
TI  - Right hepatectomy with extra-hepatic vascular division prior to transection:
      intention-to-treat analysis of a standardized policy.
AB  - BACKGROUND: Right hepatectomy (RH) is the most common type of major hepatectomy
      and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver.
      The present study reviews our standardized policy of performing RH without
      systematic PTC. METHODS: One hundred and eighty-one consecutive RH were performed
      in non-cirrhotic patients, with division of the right afferent and efferent blood
      vessels prior to transection, without systematically using PTC. Prospectively
      collected data were analysed, focusing on the following endpoints: need for
      salvage PTC, ischaemic time, blood loss and post-operative outcome. RESULTS:
      Extra-hepatic division of the right hepatic vessels was feasible in all patients,
      but was ineffective in 48 patients (26.5%) who required salvage PTC during
      transection. In those patients, the median ischaemic time was 20 min. The median
      blood loss was 500 ml (50-3000). Six patients (3.3%) experienced post-operative
      liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1%
      and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the
      only factor associated with morbidity. DISCUSSION: By performing RH with extra
      hepatic vascular division prior to transection, PTC can be safely avoided in the
      majority of patients.

PMID- 22954008
TI  - Recurrent Enterobacter cloacae septicemia, hepatic abscess, and biliary leakage
      after intra-operative radiofrequency ablation of a single liver metastasis plus
      sigmoidectomy.

PMID- 22954007
TI  - Implementation of an enhanced recovery programme following
      pancreaticoduodenectomy.
AB  - OBJECTIVES: The aim of this prospective study was to investigate the
      implementation of an enhanced recovery after surgery (ERAS) programme following
      pancreaticoduodenectomy (PD). METHODS: Patients undergoing PD were managed
      according to an ERAS protocol. Outcome measures included postoperative mortality,
      morbidity, hospitalization and 30-day readmission rate. Key protocol targets
      were: nasogastric tube (NGT) removal [postoperative day (PoD) 1]; resumption of
      oral fluids (PoD 1); urinary catheter removal (PoD 3); high-dependency unit (HDU)
      discharge (PoD 3); tolerating diet (PoD 4); drain removal (PoD 5), and hospital
      discharge (PoD 6). RESULTS: Data were collected for 50 patients (24 male; median
      age 67 years). Rates of mortality, morbidity and readmission were 4%, 46% and 4%,
      respectively. The median length of postoperative hospitalization was 10 days. The
      proportions of patients achieving key targets were: 78% for NGT removal; 82% for
      resumption of oral fluids; 48% for urinary catheter removal; 82% for HDU
      discharge; 86% for tolerating diet; 84% for meeting mobility targets, and 72% for
      drain removal. One patient was discharged by PoD 6, eight patients by PoD 7, 15
      patients by PoD 8 and 26 patients (52%) by PoD 10. Discharge was delayed in 16
      patients for social or transport-related reasons. CONCLUSIONS: The ERAS protocol
      was implemented safely. Achieving certain targets was challenging. Non-medical
      causes remain a significant factor in delayed discharge following PD.

PMID- 22954011
TI  - Total synthesis of the proposed structure of mycosporulone: structural revision
      and an unexpected retro-aldol/aldol reaction.
AB  - The proposed structure of the fungal metabolite, mycosporulone 1, was prepared
      starting from the cyclohexenone ester 11 and the D-(R)-glyceraldehyde acetonide
      12. The spectroscopic data for both 1 and its C2 epimer 1a did not match those
      reported for the natural product. A revised structure 29 for mycosporulone is
      proposed.

PMID- 22954012
TI  - Reducing strain and fracture of electrophoretically deposited CdSe nanocrystal
      films. II. Postdeposition infusion of monomers.
AB  - Thick electrophoretically deposited (EPD) films of ligand-capped colloidal
      nanocrystals (NCs) typically crack when removed from the deposition solvent due
      to the loss of residual solvent. We report the suppression of fracture in several
      micrometers thick EPD films of CdSe NCs by treating the wet, as-deposited films
      with solutions of polymer precursor monomers, followed by UV-initiated
      polymerization. The monomers diffuse into voids and, for several monomers,
      dissolve the NCs to form a uniform dispersion in the film.

PMID- 22954013
TI  - Portal vein cytokines in the early phase of acute experimental oedematous and
      necrotizing porcine pancreatitis.
AB  - OBJECTIVE: Cytokines initiate and modify systemic inflammatory response in early
      acute pancreatitis. The aim of this study was to analyze which cytokines are
      released from the pancreas to portal venous blood in the early phase of acute
      experimental necrotizing and oedematous pancreatitis and which of those cytokines
      are correlated with the more severe form of the disease. MATERIAL AND METHODS:
      Fifteen pigs were randomized to develop mild oedematous pancreatitis (n = 5,
      saline infusion to pancreatic duct), severe necrotizing pancreatitis (n = 5,
      taurocholic acid infusion) along with a control group (n = 5). Arterial and
      venous blood samples were drawn and cytokine levels were measured from portal
      vein blood at 0, 120, 240 and 360 min after the induction of pancreatitis. Tissue
      samples from the pancreas were harvested at 0 and 360 min. RESULTS: White blood
      cell count increased in necrotizing pancreatitis and the control group. The
      amount of neutrophils increased (p < 0.001) and the lymphocyte and eosinophil
      counts decreased in all groups (p < 0.001, p < 0.001). The monocyte count, as
      well as PDGF and IL-6 concentrations, increased only in necrotizing pancreatitis.
      IL-8 and eotaxin increased both in oedematous and necrotizing pancreatitis. MCP-1
      increased in all groups. IL-9, IL-4, MIP-1alpha, IFN- gamma concentrations did
      not change. Eotaxin and MCP-1 plasma levels from a previous series between portal
      venous and pulmonary arterial blood were not significantly different.
      CONCLUSIONS: The initial inflammatory process was diverse in oedematous and
      necrotizing pancreatitis. Increased monocyte count in combination with elevated
      PDGF and IL-6 are characteristic of necrotizing pancreatitis in our model.

PMID- 22954014
TI  - Intracellular Ca2+ and antioxidant values induced positive effect on
      fertilisation ratio and oocyte quality of granulosa cells in patients undergoing
      in vitro fertilisation.
AB  - Oxidative stress is important for promoting oocyte maturation and ovulation
      within the follicle through calcium ion (Ca(2+)) influx. The relationship between
      antioxidant and cytosolic Ca(2+) levels and oocyte quality and fertilisation rate
      in the granulosa cells of patients undergoing in vitro fertilisation was
      investigated. Granulosa cells were collected from 33 patients. Cytosolic free
      Ca(2+) ([Ca(2+)]i) concentration, lipid peroxidation, reduced glutathione,
      glutathione peroxidase and oocyte quality were measured in the granulosa cells.
      The relationship between two drug protocols was also examined (gonadotrophin
      releasing hormone antagonist and agonist protocols) and the same parameters
      investigated. The [Ca(2+)]i concentration (P<0.001), glutathione (P<0.05) and
      oocyte quality (P<0.001) values were significantly higher in the fertilised group
      than in the non-fertilised group, although glutathione peroxidase activity was
      significantly (P<0.05) higher in the non-fertilised group than in the fertilised
      group. The [Ca(2+)]i concentrations were also higher (P<0.001) in the good
      quality oocyte groups than in the poor-quality oocyte group. There was no
      correlation between the two drug protocols and investigated parameters. In
      conclusion, it was observed that high glutathione and cytosolic Ca(2+)
      concentrations in granulosa cells of patients undergoing in vitro fertilisation
      tended to increase the fertilisation potential of oocytes.

PMID- 22954015
TI  - A meta-analysis of host specificity in Neotropical hard ticks (Acari: Ixodidae).
AB  - Host specificity of Neotropical hard ticks (Acari: Ixodidae) was analyzed by
      using the number of hosts species for each tick species and the index of host
      specificity S(TD)*, which integrates phylogenetic and ecological information. The
      analyses were based on 4172 records of hard ticks collected from wild and
      domestic tetrapods. Most tick species included in this study were associated with
      three to 20 host species. No tick species has been associated either with a
      single species or with a single genus of host. It was found that the number of
      host species is sensitive to sampling effort, but not the S(TD)*. The most
      frequent values of S(TD)* were between 2.5 and 3.5, which shows that the host
      species more frequently used by Neotropical hard tick species belong to different
      families or different orders. Immature stages tend to use a broader taxonomic
      range of hosts than adults, and the interpretation of both measures of host
      specificity used in this study led to the conclusion that the impact of non
      endemic hosts does not alter the patterns of host specificity in Neotropical hard
      ticks. The index S(TD)* showed that a high proportion of tick species has
      phylogenetically unrelated species as principal hosts. The conclusion reached in
      this work indicates that strict host specificity is not common among Neotropical
      hard ticks and suggests that the influence of tick ecology and evolution of
      habitat specificity, tick generation time, phenology, time spent off the host and
      the type of life-cycle could be more important than hosts species.

PMID- 22954017
TI  - Clinical practice guidelines for hypothyroidism in adults: cosponsored by the
      American Association of Clinical Endocrinologists and the American Thyroid
      Association.
AB  - BACKGROUND: Hypothyroidism has multiple etiologies and manifestations.
      Appropriate treatment requires an accurate diagnosis and is influenced by
      coexisting medical conditions. This paper describes evidence-based clinical
      guidelines for the clinical management of hypothyroidism in ambulatory patients.
      METHODS: The development of these guidelines was commissioned by the American
      Association of Clinical Endocrinologists (AACE) in association with American
      Thyroid Association (ATA). AACE and the ATA assembled a task force of expert
      clinicians who authored this article. The authors examined relevant literature
      and took an evidence-based medicine approach that incorporated their knowledge
      and experience to develop a series of specific recommendations and the rationale
      for these recommendations. The strength of the recommendations and the quality of
      evidence supporting each was rated according to the approach outlined in the
      American Association of Clinical Endocrinologists Protocol for Standardized
      Production of Clinical Guidelines-2010 update. RESULTS: Topics addressed include
      the etiology, epidemiology, clinical and laboratory evaluation, management, and
      consequences of hypothyroidism. Screening, treatment of subclinical
      hypothyroidism, pregnancy, and areas for future research are also covered.
      CONCLUSIONS: Fifty-two evidence-based recommendations and subrecommendations were
      developed to aid in the care of patients with hypothyroidism and to share what
      the authors believe is current, rational, and optimal medical practice for the
      diagnosis and care of hypothyroidism. A serum thyrotropin is the single best
      screening test for primary thyroid dysfunction for the vast majority of
      outpatient clinical situations. The standard treatment is replacement with L
      thyroxine. The decision to treat subclinical hypothyroidism when the serum
      thyrotropin is less than 10 mIU/L should be tailored to the individual patient.

PMID- 22954018
TI  - A 36-month study on the cost/utility of add-on omalizumab in persistent difficult
      to-treat atopic asthma in Italy.
AB  - OBJECTIVE: Omalizumab is a biological treatment for difficult-to-treat allergic
      asthma. Its mechanism of action relies on impeding the binding of immunoglobulin
      E (IgE) to specific cellular receptors, thus blocking the inflammatory cascade.
      At present, no long-term data are available on its cost/effectiveness. The aim of
      this study is to assess long-term clinical outcomes and to measure the
      cost/utility of long-term omalizumab use in difficult-to-treat allergic
      asthmatics. METHODS: The clinical, economic, and quality-of-life (QoL) outcomes
      of 36-month add-on omalizumab therapy were compared to equivalent outcomes for
      the year before the therapy's introduction in a cohort (n = 16) of adults with
      severe uncontrolled atopic asthma on chronic high-dose antiasthma treatments. The
      variables considered were lung function, IgE levels, health status, Asthma
      Control Test (ACT) score, QoL (St. George Questionnaire), general practitioner
      (GP) and specialist visits, number and duration of hospitalizations, emergency
      room admission, and pharmacological treatment (both dose and duration). Derived
      calculated indicators were changes in health-related QoL, total healthcare costs,
      and incremental cost/utility. Data from the two periods were tested for
      statistically significant differences according to Student's t test and p < .05
      was accepted. RESULTS: Add-on omalizumab significantly and progressively improved
      asthma control and patient health-related QoL. Symptomatic drug and hospital care
      costs for these patients dropped significantly. A ?450 increase in overall
      monthly costs was observed; however, when health benefits were considered, this
      cost increase translated into an incremental cost/utility ratio of ?23,880 per
      quality-adjusted life year gained, which is quite a favorable and convenient
      figure in terms of the willingness to pay for health benefits in industrialized
      countries. CONCLUSIONS: The 36-month add-on omalizumab therapy persistently
      improved all clinical outcomes in difficult-to-treat asthmatic patients. Costs
      were also optimized and related to the extent of long-term health benefits
      achieved.

PMID- 22954019
TI  - Basic geriatric assessment does not predict in-hospital mortality after PEG
      placement.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an established procedure
      for long-term nutrition. However, studies have underlined the importance of
      proper patient selection as mortality has been shown to be relatively high in
      acute illness and certain patient groups, amongst others geriatric patients.
      Objective of the study was to gather information about geriatric patients
      receiving PEG and to identify risk factors associated with in-hospital mortality
      after PEG placement. METHODS: All patients from the GEMIDAS database undergoing
      percutaneous endoscopic gastrostomy in acute geriatric wards from 2006 to 2010
      were included in a retrospective database analysis. Data on age, gender, main
      diagnosis leading to hospital admission, death in hospital, care level, and legal
      incapacitation were extracted from the main database of the Geriatric Minimum
      Data Set. Self-care capacity was assessed by the Barthel index, and cognitive
      status was rated with the Mini Mental State Examination or subjectively judged by
      the clinician. Descriptive statistics and group comparisons were chosen according
      to data distribution and scale of measurement, logistic regression analysis was
      performed to examine influence of various factors on hospital mortality. RESULTS:
      A total of 1232 patients (60.4% women) with a median age of 82 years (range 60 to
      99 years) were included. The mean Barthel index at admission was 9.5 +/- 14.0
      points. Assessment of cognitive status was available in about half of the
      patients (n = 664), with 20% being mildly impaired and almost 70% being
      moderately to severely impaired. Stroke was the most common main diagnosis
      (55.2%). In-hospital mortality was 12.8%. In a logistic regression analysis, old
      age (odds ratio (OR) 1.030, 95% confidence interval (CI) 1.003-1.056), male sex
      (OR 1.741, 95% CI 1.216-2.493), and pneumonia (OR 2.641, 95% CI 1.457-4.792) or
      the diagnosis group 'miscellaneous disease' (OR 1.864, 95% CI 1.224-2.839) were
      identified as statistical risk factors for in-hospital death. Cognitive status
      did not have an influence on mortality (OR 0.447, CI 95% 0.248-1.650).
      CONCLUSION: In a nationwide geriatric database, no component of the basic
      geriatric assessment emerged as a significant risk factor for mortality after PEG
      placement, emphasizing individual decision-making.

PMID- 22954016
TI  - Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study.
AB  - PURPOSE: In a prospective study, Consequences of Prolonged Febrile Seizures in
      Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)-6 and
      HHV-7 infection as a cause of febrile status epilepticus (FSE). METHODS: Children
      ages 1 month to 5 years presenting with FSE were enrolled within 72 h and
      received a comprehensive assessment including specimens for HHV-6 and HHV-7. The
      presence of HHV-6A, HHV-6B, or HHV-7 DNA and RNA (amplified across a spliced
      junction) determined using quantitative polymerase chain reaction (qPCR) at
      baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in
      conjunction with the PCR results to distinguish primary infection from
      reactivated or prior infection. KEY FINDINGS: Of 199 children evaluated, HHV-6 or
      HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was
      found in 54 children (32.0%), including 38 with primary infection and 16 with
      reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at
      baseline was observed in 12 children (7.1%), including eight with primary
      infection and four with reactivated infection. Two subjects had HHV-6/HHV-7
      primary coinfection at baseline. There were no differences in age,
      characteristics of illness or fever, seizure phenomenology or the proportion of
      acute EEG or imaging abnormalities in children presenting with FSE with or
      without HHV infection. SIGNIFICANCE: HHV-6B infection is commonly associated with
      FSE. HHV-7 infection is less frequently associated with FSE. Together, they
      account for one third of FSE, a condition associated with an increased risk of
      both hippocampal injury and subsequent temporal lobe epilepsy.

PMID- 22954020
TI  - Effect of mental fatigue on the central nervous system: an electroencephalography
      study.
AB  - BACKGROUND: Fatigue can be classified as mental and physical depending on its
      cause, and each type of fatigue has a multi-factorial nature. We examined the
      effect of mental fatigue on the central nervous system using
      electroencephalography (EEG) in eighteen healthy male volunteers. METHODS: After
      enrollment, subjects were randomly assigned to two groups in a single-blinded,
      crossover fashion to perform two types of mental fatigue-inducing experiments.
      Each experiment consisted of four 30-min fatigue-inducing 0- or 2-back test
      sessions and two evaluation sessions performed just before and after the fatigue
      inducing sessions. During the evaluation session, the participants were assessed
      using EEG. Eleven electrodes were attached to the head skin, from positions F3,
      Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, and O2. RESULTS: In the 2-back test, the beta
      power density on the Pz electrode and the alpha power densities on the P3 and O2
      electrodes were decreased, and the theta power density on the Cz electrode was
      increased after the fatigue-inducing mental task sessions. In the 0-back test, no
      electrodes were altered after the fatigue-inducing sessions. CONCLUSIONS:
      Different types of mental fatigue produced different kinds of alterations of the
      spontaneous EEG variables. Our findings provide new perspectives on the neural
      mechanisms underlying mental fatigue.

PMID- 22954021
TI  - Solvent-free synthesis of zeolites from solid raw materials.
AB  - As important industrial materials, microporous zeolites are necessarily
      synthesized in the presence of solvents such as in hydrothermal, solvothermal,
      and ionothermal routes. We demonstrate here a simple and generalized solvent-free
      route for synthesizing various types of zeolites by mixing, grinding, and heating
      solid raw materials. Compared with conventional hydrothermal route, the avoidance
      of solvents in the synthesis not only significantly reduces the waste production,
      but also greatly increases the yield of zeolite products. In addition, the use of
      starting solid raw materials remarkably enhances the synthesis efficiency and
      reduces the use of raw materials, energy, and costs.

PMID- 22954022
TI  - Highly-efficient gating of solid-state nanochannels by DNA supersandwich
      structure containing ATP aptamers: a nanofluidic IMPLICATION logic device.
AB  - Integrating biological components into artificial devices establishes an
      interface to understand and imitate the superior functionalities of the living
      systems. One challenge in developing biohybrid nanosystems mimicking the gating
      function of the biological ion channels is to enhance the gating efficiency of
      the man-made systems. Herein, we demonstrate a DNA supersandwich and ATP gated
      nanofluidic device that exhibits high ON-OFF ratios (up to 10(6)) and a perfect
      electric seal at its closed state (~GOmega). The ON-OFF ratio is distinctly
      higher than existing chemically modified nanofluidic gating systems. The gigaohm
      seal is comparable with that required in ion channel electrophysiological
      recording and some lipid bilayer-coated nanopore sensors. The gating function is
      implemented by self-assembling DNA supersandwich structures into solid-state
      nanochannels (open-to-closed) and their disassembly through ATP-DNA binding
      interactions (closed-to-open). On the basis of the reversible and all-or-none
      electrochemical switching properties, we further achieve the IMPLICATION logic
      operations within the nanofluidic structures. The present biohybrid nanofluidic
      device translates molecular events into electrical signals and indicates a built
      in signal amplification mechanism for future nanofluidic biosensing and modular
      DNA computing on solid-state substrates.

PMID- 22954023
TI  - In situ time-resolved X-ray near-edge absorption spectroscopy of selenite
      reduction by siderite.
AB  - The reduction-oxidation reaction between aqueous selenite (SeO(3)(2-)) and
      siderite (FeCO(3(s))) was monitored by in situ, time-resolved X-ray absorption
      near-edge structure (XANES) spectroscopy at the selenium K edge in a controlled
      electrochemical environment. Spectral evolutions showed that more than 60% of
      selenite was reduced at the siderite surface after 20 h of experiment, at which
      time the reaction was still incomplete. Fitting of XANES spectra by linear
      combination of reference spectra showed that selenite reaction with siderite is
      essentially a two-step process, selenite ions being immobilized on siderite
      surface prior to their reduction. A kinetic model of the reduction step is
      proposed, allowing to identify the specific contribution of surface reduction.
      These results have strong implications for the retention of selenite by corrosion
      products in nuclear waste repositories and in a larger extent for the fate of
      selenium in the environment.

PMID- 22954024
TI  - Are biological targets the final goal for rheumatoid arthritis therapy?
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder
      that is characterized by inflammation of synovial membrane and the release of
      inflammatory cytokines that ultimately results in joint destruction and
      disability. The therapeutic treatment plan for treating RA patient initiates with
      disease-modifying antirheumatic agents (DMARDs) and ends with the use of
      biological agents. Sometimes a combination of DMARDs and the biological agents
      are aggressively initiated. But this is not sufficient to retard the underlying
      progression of the disease and hence the disease-associated pain persists. The
      solution lies in the treatment of causative factors. Modern therapy aims at
      targeting newer target sites that can not only overcome the problem of pain and
      disability but also minimize the occurrence of adverse effects faced by the
      traditional therapeutic approach. AREAS COVERED: This review covers the
      pathological background of the disease in brief, the traditional and newer
      biologicals, therapeutic targets and novel therapies for rheumatoid arthritis.
      EXPERT OPINION: Better management of the disease can be achieved by focusing on
      the causes and the factors of the disease. Newer therapies and targeting sites
      discussed in this review focus on treating the disability at the cellular level
      without affecting body's immune response and minimizing the chances of infection
      and inflammation.

PMID- 22954025
TI  - In vivo dog intestinal precipitation of mebendazole: a basic BCS class II drug.
AB  - The purpose of this study was to investigate in vivo intestinal precipitation of
      a model drug mebendazole, a basic BCS class II drug, using dogs with intestinal
      stomas for administration or sampling. After oral administration of a solution
      with an expected intestinal supersaturation of approximately 20 times the
      solubility, the measured supersaturation in dog intestinal fluid (DIF) was up to
      10 times and, on average, only 11% of the given dose was retrieved as solid drug
      in the collected fluid from the stoma. The drug was rapidly absorbed with >90% of
      the total systemic exposure reached within three hours after duodenal
      administration of a solution. In silico absorption modeling showed that in vivo
      data were reasonably well described by a nonprecipitating solution. An in vitro
      model of precipitation in DIF predicted that the intestinal concentration of
      dissolved mebendazole would be less than 1/5 of the initial concentration within
      10 min at concentrations comparable to in vivo. It was concluded that intestinal
      precipitation did not have any major influence on mebendazole absorption. The
      extent of precipitation was overpredicted in vitro given the in vivo absorption
      rate, and further work is needed to identify in vitro factors that could enable
      more accurate in vivo predictions of intestinal precipitation from solutions.

PMID- 22954026
TI  - Human antibody fragments specific for Bothrops jararacussu venom reduce the
      toxicity of other Bothrops sp. venoms.
AB  - Approximately 20,000 snakebites are registered each year in Brazil. The classical
      treatment for venomous snakebite involves the administration of sera obtained
      from immunized horses. Moreover, the production and care of horses is costly, and
      the use of heterologous sera can cause hypersensitivity reactions. The production
      of human antibody fragments by phage display technology is seen as a means of
      overcoming some of these disadvantages. The studies here attempted to test human
      monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp.
      venoms, using the Griffin.1 library of human single-chain fragment-variable
      (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this
      laboratory previously produced scFvs capable of inhibiting the phospholipase and
      myotoxic activities of Bothrops jararacussu venom. The structural and functional
      similarities of the various forms of phospholipase A2 (PLA2) in Bothrops venom
      served as the basis for the present study wherein the effectiveness of those same
      scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms.
      Each clone was found to recognize all three Bothrops venoms, and purified scFvs
      partially inhibited their in vitro phospholipase activity. In vivo assays
      demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the
      survival of animals that received the test venoms. The results here indicate that
      the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to
      produce a human anti-bothropic sera. This data demonstrates that the human scFv
      P2B7 represents an alternative therapeutic approach to heterologous anti
      bothropic sera available today.

PMID- 22954028
TI  - A review of minimally invasive single-port/incision laparoscopic appendectomy.
AB  - INTRODUCTION: Single-port/incision laparoscopic appendectomy (SPILA) is a modern
      advancement toward stealth surgery, using a single point of entry. Despite the
      paucity of clinical data, it is increasingly being used to minimize scarring and,
      potentially, pain associated with the multiple entry points. We aimed to
      summarize and present available data on this new approach. METHODOLOGY: All
      available databases until December 2010 including the Cochrane Controlled Trials
      Register, MEDLINE, and EMBASE were searched and cross-referenced for studies
      describing single-incision laparoscopic appendectomy. Case and experimental
      reports, series with fewer than 5 patients, and non-English articles were
      excluded. Outcome measures were operative time, postoperative hospital stay, pain
      scores, complications, conversion, and mortality, stratified according to type of
      SPILA approach. SPSS version 18.0.0 software was used for data collection.
      RESULTS: Database query yielded 79 articles; 45 were included (1 randomized
      controlled trial, 44 case series). Total cases were 2806, with mean patient age
      for studies ranging from 7.0 to 37.5 years. No mortality was reported. The
      overall complication rate was 4.13%. The overall weighted mean operating time was
      41.3 minutes (range, 15.0-95.9 minutes). The weighted mean hospital stay was 2.79
      days (range, 1.0-6.6 days). CONCLUSIONS: Although the incidence of complications
      with SPILA remains low and operating times between new and traditional approaches
      are comparable in case-based literature, adequately powered randomized trials are
      required to assess its effectiveness. Occurrence of long-term complication types
      remains unexplored.

PMID- 22954027
TI  - Study protocol: to investigate effects of highly specialized rehabilitation for
      patients with multiple sclerosis. A randomized controlled trial of a
      personalized, multidisciplinary intervention.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex, chronic and progressive disease
      and rehabilitation services can provide important support to patients. Few MS
      rehabilitation programs have been shown to provide health improvements to
      patients in a cost-effective manner. The objective of this study is to assess the
      effects in terms of changes measured by a variety of standardized quality of
      life, mastery, coping, compliance and individual goal-related endpoints. This
      combination provides the basis for analyzing the complexity of MS and outcomes of
      a personalized rehabilitation. METHODS/DESIGN: Patients with MS referred to
      hospital rehabilitation services will be randomized to either early admission
      (within two months) or usual admission (after an average waiting time of eight
      months). They will complete a battery of standardized health outcome instruments
      prior to randomization, and again six and twelve months after randomization, and
      a battery of goal-related outcome measures at admission and discharge, and again
      one, six and twelve months after randomization. DISCUSSION: The results of the
      study are expected to contribute to further development of MS rehabilitation
      services and to discussions about the design and content of such services. The
      results will also provide additional information to health authorities
      responsible for providing and financing rehabilitation services. TRIAL
      REGISTRATION: Current Controlled Trials (ISRCTN05245917).

PMID- 22954029
TI  - Advancing age within established Gleason score categories and the risk of
      prostate cancer-specific mortality (PCSM).
AB  - Study Type - Prognosis (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? There is limited data that suggests that
      men aged >70 years have a higher proportion of Gleason 8-10 prostate cancer than
      men aged <70 years, as well as a higher risk of PSA recurrence, distant
      metastases, and disease-specific death on univariate analysis. The present study
      shows that older as compared with younger men with Gleason score 6 and 7 prostate
      cancer have an increased risk of prostate cancer-specific mortality. This may be
      due to the presence of occult high-grade disease and suggests further diagnostic
      studies, e.g. multiparametric MRI, may be indicated in these men to reduce biopsy
      sampling error. OBJECTIVE: To determine if advancing age is a risk factor for
      high-grade prostate cancer due to occult high-grade disease in elderly men with
      Gleason score 6 or 7 prostate cancer. We investigated whether advancing age is
      associated with the risk of prostate cancer-specific mortality (PCSM) within
      established Gleason score categories adjusting for known predictors of PCSM.
      PATIENTS AND METHODS: Using data from the Surveillance, Epidemiology and End
      Results database between 1 January 2004 to 31 December 2007, 166 104 men with non
      metastatic prostate cancer were identified and formed the study cohort. * Within
      established Gleason score categories, Fine and Gray's multivariable competing
      risk regressions were used to evaluate whether increasing age at diagnosis was
      significantly associated with an increased risk of PCSM, adjusting for prostate
      specific antigen level and T-category at diagnosis and whether treatment was
      curative or non-curative. RESULTS: After adjusting for treatment and prognostic
      factors, Gleason score 8-10 and 7 as compared with <=6 was associated with an
      increased risk of PCSM (P < 0.001). * Increasing age was associated with an
      increased risk of PCSM only in Gleason score 6 (adjusted hazard ratio [AHR] 1.06,
      95% confidence interval [CI] 1.04-1.08, P < 0.001) and 7 (AHR 1.02, 95% CI 1.01
      1.03, P < 0.001), but not with Gleason score 8-10 (AHR 0.999, 95% CI 0.995-1.003,
      P= 0.61). * These risks were highest in men aged >70 years having Gleason score 6
      (AHR 1.10, 95% CI 1.07-1.13, P < 0.001) and Gleason score 7 prostate cancer (AHR
      1.04, 95% CI 1.02-1.06, P < 0.001). CONCLUSIONS: PCSM increases with advancing
      age in men with Gleason score 6 and 7 but not 8-10 prostate cancer. * Techniques
      to reduce biopsy sampling error in men, particularly those aged >70 years and
      healthy with Gleason score 6 and 7 disease deserve further study.

PMID- 22954030
TI  - Bladder augmentation using bowel segments (enterocystoplasty).

PMID- 22954031
TI  - Important surgical considerations in the management of renal cell carcinoma (rcc)
      with inferior vena cava (ivc) tumour thrombus.

PMID- 22954033
TI  - Robotic radical prostatectomy as the initial step in multimodal therapy for men
      with high-risk localised prostate cancer: initial experience of 160 men.

PMID- 22954034
TI  - Turnover-dependent covalent inactivation of Staphylococcus aureus coenzyme A
      disulfide reductase by coenzyme A-mimetics: mechanistic and structural insights.
AB  - Disruption of the unusual thiol-based redox homeostasis mechanisms in
      Staphylococcus aureus represents a unique opportunity to identify new metabolic
      processes and new targets for intervention. Targeting uncommon aspects of CoASH
      biosynthetic and redox functions in S. aureus, the antibiotic CJ-15,801 has
      recently been demonstrated to be an antimetabolite of the CoASH biosynthetic
      pathway in this organism; CoAS-mimetics containing alpha,beta-unsaturated sulfone
      and carboxyl moieties have also been exploited as irreversible inhibitors of S.
      aureus coenzyme A-disulfide reductase (SaCoADR). In this work we have determined
      the crystal structures of three of these covalent SaCoADR-inhibitor complexes,
      prepared by inactivation of wild-type enzyme during turnover. The structures
      reveal the covalent linkage between the active-site Cys43-S(gamma) and C(beta) of
      the vinyl sulfone or carboxyl moiety. The full occupancy of two inhibitor
      molecules per enzyme dimer, together with kinetic analyses of the wild-type/C43S
      heterodimer, indicates that half-sites-reactivity is not a factor during normal
      catalytic turnover. Further, we provide the structures of SaCoADR active-site
      mutants; in particular, Tyr419'-OH plays dramatic roles in directing
      intramolecular reduction of the Cys43-SSCoA redox center, in the redox asymmetry
      observed for the two FAD per dimer in NADPH titrations, and in catalysis. The two
      conformations observed for the Ser43 side chain in the C43S mutant structure lend
      support to a conformational switch for Cys43-S(gamma) during its catalytic Cys43
      SSCoA/Cys43-SH redox cycle. Finally, the structures of the three inhibitor
      complexes provide a framework for design of more effective inhibitors with
      therapeutic potential against several major bacterial pathogens.

PMID- 22954035
TI  - Second line options for hyperlipidemia management after cardiac transplantation.
AB  - Despite widespread statin therapy, 91% of cardiac transplant patients have
      hyperlipidemia within 5 years from cardiac transplantation. The implications of
      this are profound, particularly given that coronary allograft vasculopathy is a
      leading cause of death. Unfortunately the solution is not easy, with problems of
      toleration at higher statin doses and a lack of good quality evidence for second
      line agents. We review the literature and discuss some of the key issues
      transplant physicians are faced with when considering alternatives to statin
      therapy.

PMID- 22954036
TI  - Epidemiology, natural history and risk factors for anal intraepithelial
      neoplasia.
AB  - Studies conducted in HIV-seropositive individuals have enhanced our understanding
      of the natural history of anal intraepithelial neoplasia (AIN) and of factors
      predictive of progression to high-grade AIN, the immediate precursor to anal
      cancer. AIN is frequently detected in HIV-seropositive individuals. Factors that
      increase the risk for AIN include HIV infection, low current or nadir blood CD4+
      cell counts, receptive anal intercourse, oncogenic human papillomavirus (HPV)
      infection, persistent anal HPV infection, multiple HPV type infections and high
      anal HPV viral load. This review confirms the importance of high-grade AIN in HIV
      seropositive individuals and HIV-seronegative men having sex with men.

PMID- 22954037
TI  - Ionic liquids induced structural changes of bovine serum albumin in aqueous
      media: a detailed physicochemical and spectroscopic study.
AB  - Structural changes of a globular protein, bovine serum albumin (BSA), as a
      consequence of interaction with the surface active ionic liquids (ILs)-3-methyl-1
      octylimidazolium chloride, [C(8)mim][Cl], and 1-butyl-3-methylimidazolium
      octylsulfate, [C(4)mim][C(8)OSO(3)]-have been investigated using various
      physicochemical and spectroscopic techniques such as tensiometry, conductometry,
      steady-state fluorescence, far-UV circular dichroism spectroscopy (CD), and
      dynamic light scattering (DLS). The interactional behavior of ILs (monomers and
      self-assembled structures) toward BSA in different IL concentration regimes at
      the air/solution interface as well as in the bulk is investigated and discussed
      depending upon the nature of ions of ILs. CD combined with the steady state
      fluorescence spectroscopy provided valuable insights into the unfolding of BSA as
      a consequence of IL binding. The complementary results obtained from the
      multitechnique approach proved very useful in drawing out the mechanism of
      interaction between ILs and BSA in different IL concentration regimes.

PMID- 22954039
TI  - Nuclear quadrupole coupling constants for N2O: experiment and theory.
AB  - The nuclear quadrupole coupling constants (NQCCs) for the nitrogen and oxygen
      nuclei in N(2)O have been determined using a variety of computational methods
      (MP2, QCISD, DFT with B3LYP, PBE0, and B3PW91 functionals, CCSD, CCSD(T), CASSCF,
      and MRCI) combined with correlation-consistent basis sets. When compared to the
      available experimental determinations, the results demonstrate that only CCSD(T)
      and MRCI methods are capable of accurately predicting the NQCCs of the central
      and terminal nitrogen atoms. The spin-rotation and magnetic shielding tensors
      have also been determined and compared to experimental measurements where
      available. (14)N and (17)O NMR relaxation data for N(2)O in the gas phase and a
      variety of solvents is reported. The increase in the ratio of (14)N spin-lattice
      relaxation times in solvent for the central and terminal nitrogens supports
      previous reports of the modification of the electric field gradients at these
      nuclei in van der Waals complexes. Ab initio computations for the linear
      FH...N(2)O complex confirm the large change in EFGs imposed by a single
      perturber.

PMID- 22954038
TI  - Prevention of pneumococcal diseases in the post-seven valent vaccine era: a
      European perspective.
AB  - BACKGROUND: The burden of invasive pneumococcal disease in young children
      decreased dramatically following introduction of the 7-valent pneumococcal
      conjugate vaccine (PCV7). The epidemiology of S. pneumoniae now reflects
      infections caused by serotypes not included in PCV7. Recently introduced higher
      valency pneumococcal vaccines target the residual burden of invasive and non
      invasive infections, including those caused by serotypes not included in PCV7.
      This review is based on presentations made at the European Society of Pediatric
      Infectious Diseases in June 2011. DISCUSSION: Surveillance data show increased
      circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7 F and 19A in
      countries with routine vaccination. Preliminary evidence suggests that broadened
      serotype coverage offered by higher valency vaccines may be having an effect on
      invasive disease caused by some of those serotypes, including 19A, 7 F and 6C.
      Aetiology of community acquired pneumonia remains a difficult clinical diagnosis.
      However, recent reports indicate that pneumococcal vaccination has reduced
      hospitalisations of children for vaccine serotype pneumonia. Variations in
      serotype circulation and occurrence of complicated and non-complicated pneumonia
      caused by non-PCV7 serotypes highlight the potential of higher valency vaccines
      to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute
      otitis media (AOM) caused by vaccine serotypes. Recent investigations of the
      interaction between S. pneumoniae and non-typeable H. influenzae suggest that
      considerable reduction in severe, complicated AOM infections may be achieved by
      prevention of early pneumococcal carriage and AOM infections. Extension of the
      vaccine serotype spectrum beyond PCV7 may provide additional benefit in
      preventing the evolution of AOM. The direct and indirect costs associated with
      pneumococcal disease are high, thus herd protection and infections caused by non
      vaccine serotypes both have strong effects on the cost effectiveness of
      pneumococcal vaccination. Recent evaluations highlight the public health
      significance of indirect benefits, prevention of pneumonia and AOM and coverage
      of non-PCV7 serotypes by higher valency vaccines. SUMMARY: Routine vaccination
      has greatly reduced the burden of pneumococcal diseases in children. The
      pneumococcal serotypes present in the 7-valent vaccine have greatly diminished
      among disease isolates. The prevalence of some non-vaccine serotypes (e.g. 1, 7 F
      and 19A) has increased. Pneumococcal vaccines with broadened serotype coverage
      are likely to continue decreasing the burden of invasive disease, and community
      acquired pneumonia in children. Further reductions in pneumococcal carriage and
      increased prevention of early AOM infections may prevent the evolution of severe,
      complicated AOM. Evaluation of the public health benefits of pneumococcal
      conjugate vaccines should include consideration of non-invasive pneumococcal
      infections, indirect effects of vaccination and broadened serotype coverage.

PMID- 22954040
TI  - Holocaust victims and perpetrators.
AB  - The author presents here the results of 12 years of work with a group of
      psychotherapists in Germany on the subject of the after-effects of the Nazi
      period on people in psychotherapeutic treatment today. She identifies several
      typical complexes concerned with issues of identity, loyalty, relationship,
      authority and aggression. Case examples and references to texts from the Nazi
      period illustrate the phenomena. The author's concern is that psychotherapists be
      aware of their own collective (family, ethnic, national) past so that they can
      fully engage in their work without having to repress painful collective
      complexes. In training analysis this aspect of the work is especially important
      so that the following generations of analysts can experience the importance of
      this level of the collective unconscious.

PMID- 22954041
TI  - Monuments of memory: defensive mechanisms of the collective psyche and their
      manifestation in the memorialization process.
AB  - The paper searches for insight in the area of collective memory as a part of
      collective consciousness, a phenomenon understood as a stabilizing factor for a
      society's self-image and identity. Collective memories are seen as originating
      from shared communications transmitting and creating the meaning of the past in
      the form of narrative, symbols and signs. As such, they contain the individual,
      embodied and lived side of our relations to the past. As well as the identity
      building and meaning-making functions of collective memories, their defensive
      function is discussed with a focus on commemorative practices taking place in a
      transitional space between psychic and social life. Fears of a lack of collective
      identity and coherence have contributed to the way Polish commemorative practices
      have been shaped. This is considered in relation to the Smolensk catastrophe in
      2010, viewed in the context of the Jungian concept of the collective psyche and
      the psychoanalytical understanding of defensive group mechanisms against trauma,
      especially those relating to loss and mourning. It leads to a consideration of
      how historical experiences and the experience of history can be accessed, as well
      as their meaning for individual and group development.

PMID- 22954042
TI  - Redeeming the lost voice of the ancestors.
AB  - The Holocaust of the Jews in World War II involved not only the murder of 6
      million Jews but also the traumatic destruction and wipe-out of whole
      communities, with their rich culture and tradition which had existed for
      centuries. In places where no one survived, it was almost impossible to
      reconstruct the collective memory of those communities. The voice of the
      ancestors was lost. As a daughter of Holocaust survivors, I have always felt the
      strong presence of the loss, not only of the murdered family members but also of
      the ancient colourful world of Eastern European Jews. I have always felt
      compelled to link back to that lost world. In the past three years, my journey to
      the pre-war past has become more intense. This article describes the double role
      of my journey: it is both an attempt to reconstruct, redeem and preserve the
      memory of the lost ancestors, and a personal journey to the echoes of my
      ancestors' voices within my soul.

PMID- 22954043
TI  - The Red Book and clinical practice.
AB  - Jung's work is fundamentally an experience, not an idea. From this perspective, I
      attempt to bridge conference, consulting room and living psyche by considering
      the influence of the 'Red Book' on clinical practice through the subtle and
      imaginal. Jung's journey as a man broadens out to have relevance for women. His
      story is individual but its archetypal foundation finds parallel expression in
      analytic practice today.

PMID- 22954044
TI  - Clinical implications of The Red Book.
AB  - This presentation stresses the uniqueness of both the therapist's and patient's
      personal experience in clinical work and relates this to the significance of The
      Red Book as Jung's personal odyssey and for me personally as an analyst. I
      consider The Red Book's enduring relevance alongside recent psychological
      theories, neuroscience and early mystical writings, and conclude with a clinical
      vignette of a patient's response to a piece of choral music and subsequent use of
      active imagination.

PMID- 22954045
TI  - Clinical implications of The Red Book: Liber Novus.
AB  - In this presentation I consider whether the importance of Spirit in Liber Novus
      may render the task of its clinical application peculiarly problematic. Freud's
      experimentation on himself is briefly compared with Jung's self-experimentation
      of which Liber Novus is the record. Taking up the theme of the vas from
      Gaillard's paper, I refer to Jung's two major contributions to the elaboration of
      the Freudian frame: the necessity for the analyst to have been analysed, and the
      positive value of countertransference. In an epilogue, I briefly discuss a dream
      related to the preparation of this report for publication, emphasizing the theme
      of the disturbing effects of Spirit as a key theme both in Liber Novus itself and
      in any attempt to assimilate it on the part of the contemporary analyst.

PMID- 22954047
TI  - Narcissism, solitude, friendship: notes on the therapeutic alliance in the
      context of the Freud-Jung relationship.
AB  - This paper deals with friendship and therapeutic alliance as a transformation of
      the libidinal love that structures the Oedipal complex. The author considers the
      relationship between Jung and Freud as a formidable test that may shed light on
      their personalities and on the relevance of the Oedipal complex for both of them
      and for their particular theories and practices. The author discusses the
      possibility that the Oedipal complex may be seen under a finalistic frame of
      reference and discusses which implicit goals it may express. Such a goal has not
      been reached by either Freud nor Jung, but might be the key to underline and
      recognize the fundamental importance of the 'therapeutic alliance' within the
      analytical situation, seen as a potential relationship between the selves of the
      patient and of the analyst springing from a transformation of libidinal love into
      'friendship' as it was described by Friedrich Nietzsche.

PMID- 22954048
TI  - A serious misunderstanding: synchronicity and the generation of meaning.
AB  - This paper points to the problem caused by the fact that numerous academic 'Jung
      studies' are conducted on the basis of the English translation of Jung's works
      without any knowledge of his original texts and illustrates it with the
      misconstrual that Jung's concept of synchronicity suffered in the studies of many
      recent authors, as exemplified by two articles in the September 2011 issue of the
      JAP. The translation of 'sinngemabetae Koinzidenz' as 'meaningful coincidence'
      seduced those writers to take synchronistic 'meaning' as meaning the
      meaningfulness of life or even as 'transcendent meaning', which is incompatible
      with Jung's synchronicity concept, and to replace Jung's strictly intellectual
      project of establishing an explanatory principle for synchronistic events (in
      addition to the principle of causality for all other events) by the fundamentally
      different project of focusing on the impact that such events may have for the
      experiencing subjective mind, on 'human meaning-making', and, with a decidedly
      anti-intellectual bias, of hoping for 'shifts into non-rational states of mind'.

PMID- 22954056
TI  - Philadelphia freedom.

PMID- 22954057
TI  - Prevalence, disparities, and trends in obesity and severe obesity among students
      in the Philadelphia, Pennsylvania, school district, 2006-2010.
AB  - INTRODUCTION: Epidemic increases in obesity negatively affect the health of US
      children, individually and at the population level. Although surveillance of
      childhood obesity at the local level is challenging, height and weight data
      routinely collected by school districts are valuable and often underused public
      health resources. METHODS: We analyzed data from the School District of
      Philadelphia for 4 school years (2006-2007 through 2009-2010) to assess the
      prevalence of and trends in obesity and severe obesity among public school
      children. RESULTS: The prevalence of obesity decreased from 21.5% in 2006-2007 to
      20.5% in 2009-2010, and the prevalence of severe obesity decreased from 8.5% to
      7.9%. Both obesity and severe obesity were more common among students in grades 6
      through 8 than among children in lower grades or among high school students.
      Hispanic boys and African American girls had the highest prevalence of obesity
      and severe obesity; Asian girls had much lower rates of obesity and severe
      obesity than any other group. Although obesity and severe obesity declined during
      the 4-year period in almost all demographic groups, the decreases were generally
      smaller in the groups with the highest prevalence, including high school
      students, Hispanic males, and African American females. CONCLUSION: Although
      these data suggest that the epidemic of childhood obesity may have begun to
      recede in Philadelphia, unacceptably high rates of obesity and severe obesity
      continue to threaten the health and futures of many school children.

PMID- 22954058
TI  - Impedance baseline and reflux perception in responder and non-responder non
      erosive reflux disease patients.
AB  - BACKGROUND: It was recently shown that GERD patients have lower impedance
      baseline (IB) values than healthy controls and, that the esophageal acid exposure
      time (AET) correlates with IB levels. GOALS: To explore the sensitivity of IB
      measurements in NERD patients, responders and non-responders to PPIs, when
      compared with pH-impedance (MII-pH) variables, and to evaluate whether this
      variable could represent a marker of GERD symptoms. Reproducibility and inter
      observer agreement of IB measurement were also assessed. Study. MII-pH tracings
      from 44 NERD responders and 22 non-responders were analysed. Ten healthy
      volunteers underwent the same protocol. IB values were measured at the distal and
      proximal esophagus. IB was also analysed in a subgroup of patients and in
      controls with two methods and by two blinded operators. RESULTS: Mean IB values
      at the distal esophagus were significantly lower in NERD patients than in
      controls. IB values did not differ between responders and non-responders. Of the
      8 responders with negative AET and symptom association probability (SAP), 3
      (37.5%) showed IB values lower than controls. IB values in responders with
      positive and negative SAP were similar (1832 (1596-2068) Omega vs 1667 (1361
      1973) Omega, p: n.s.). No differences were found between the IB values measured
      with the two methods and the inter-observer agreement was good. CONCLUSIONS: IB
      is a promising and easy to calculate MII-pH variable and appears to increase the
      sensitivity of MII-pH monitoring. IB values cannot predict PPI response and are
      not associated with reflux perception in NERD patients.

PMID- 22954059
TI  - Living cardiac patch: the elixir for cardiac regeneration.
AB  - INTRODUCTION: A thorough understanding of the cellular and muscle fiber
      orientation in left ventricular cardiac tissue is of paramount importance for the
      generation of artificial cardiac patches to treat the ischemic myocardium. The
      major challenge faced during cardiac patch engineering is to choose a perfect
      combination of three entities; cells, scaffolds and signaling molecules
      comprising the tissue engineering triad for repair and regeneration. AREAS
      COVERED: This review provides an overview of various scaffold materials, their
      mechanical properties and fabrication methods utilized in cardiac patch
      engineering. Stem cell therapies in clinical trials and the commercially
      available cardiac patch materials were summarized in an attempt to provide a
      recent perspective in the treatment of heart failure. Various tissue engineering
      strategies employed thus far to construct viable thick cardiac patches is
      schematically illustrated. EXPERT OPINION: Though many strategies have been
      proposed for fabrication of various cardiac scaffold materials, the stage and
      severity of the disease condition demands the incorporation of additional cues in
      a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or
      custom designed films. Integration of stem cells and biomolecular cues along with
      the scaffold may provide the right microenvironment for the repair of unhealthy
      left ventricular tissue as well as promote its regeneration.

PMID- 22954060
TI  - Estimating the economic benefits of positive shifts in fibromyalgia severity: an
      exploratory analysis based on modeling of clinical trial data of pregabalin.
AB  - OBJECTIVE: To estimate the annualized differences in direct medical and indirect
      costs associated with improvement in fibromyalgia (FM) severity among pregabalin
      treated patients. METHODS: Data from three clinical trials of pregabalin in
      patients with FM were modeled; efficacy results were extrapolated. Mean annual
      costs (direct and indirect) were assigned based on FM severity levels (mild:
      $10,219; moderate: $26,217; severe: $42,456). FM severity levels were defined
      using established cut-points on the Fibromyalgia Impact Questionnaire (FIQ). Mean
      annualized costs at end-point were estimated for all patients within each cohort
      and the mean differences in costs were compared using a regression model.
      RESULTS: Relative to placebo, there was a significantly higher proportion of
      subjects with mild FM at end-point with pregabalin 450 mg and a significantly
      lower proportion of subjects with severe FM. Mean total costs were lower with
      pregabalin (300 mg, $25,721; 450 mg, $24,103) than placebo ($26,162). The
      difference in mean annual costs was $2059 lower for pregabalin 450 mg (p = 0.003)
      and $441 lower for pregabalin 300 mg (p = 0.52). Mean direct medical costs were
      higher with pregabalin (300 mg, $4962; 450 mg, $4820) than placebo ($4364). The
      difference in mean annual direct medical costs was significantly higher for
      pregabalin 450 mg by $456 (p < 0.0001) and by $599 for pregabalin 300 mg (p <
      0.0001). Mean indirect costs for pregabalin (300 mg, $20,783; 450 mg, $19,306)
      were lower than placebo ($21,735). The difference in mean annual indirect costs
      for pregabalin 450 mg was lower by $2429 (p < 0.0001); pregabalin 300 mg was
      lower by $951 (p = 0.12). LIMITATIONS: Use of 13-week end-point data from
      clinical trials to extrapolate to annual costs and an assumption of continuous
      therapy over the course of 1 year. CONCLUSIONS: Improvements in FM severity were
      associated with overall reductions in cost. Reductions in indirect costs may
      offset the costs of treatment with pregabalin.

PMID- 22954061
TI  - Medicare patient experience with vagus nerve stimulation for treatment-resistant
      depression.
AB  - BACKGROUND: Major depressive disease (MDD) represents a cost burden to the US
      healthcare system: approximately one-third of MDD patients fail conventional
      treatment: multiple failures define treatment-resistant depression (TRD). Vagus
      nerve stimulation (VNS) therapy is an approved adjunctive treatment for TRD.
      OBJECTIVE: To study the healthcare utilization experience of Medicare
      beneficiaries implanted with VNS (VNSBs) during Medicare coverage, compared with
      beneficiaries with TRD (TRDBs) and managed depression (Mdeps). METHODS: A
      retrospective analysis of 100% standard analytic file (SAF) Medicare claims from
      2006-2009 using specific criteria to identify a VNSB dataset, compared to TRDs
      and Mdeps datasets (extract of 5% sample SAF from 2001-2009) and 2009 general
      Medicare beneficiaries (GMBs). Comparative analysis included demographics,
      mortality, healthcare utilization, and costs. RESULTS: Among patients meeting
      study criteria for VNSBs (n = 690), TRDBs (n = 4639), Mdeps (n = 7524), and GMBs
      (n > 36 million), VNSBs were on average: younger, more likely to be female, and
      white, with Medicare eligibility due to disability. Of the VNSBs in the 2-year
      post-implantation period: 5% died; 22% experienced no negative events (defined as
      hospitalizations for psychoses or poisoning, emergency room use,
      electroconvulsive therapy, or poisoning, suicidal ideation, or self-harm
      diagnoses); 29% experienced multiple negative events; and 41% had either a single
      hospitalization or only all-cause ER visits. VNSBs experiencing negative events
      had more complex co-occurring psychiatric diagnoses. The annual mortality rate
      for VNSBs post-implant was 19.9 deaths per 1000 patient years, compared with 46.2
      (CI: 41.9-51.6) and 46.8 (CI: 43.4-50.4) deaths for TRDBs and Mdeps,
      respectively. The medical costs per patient-year post-VNS implantation for VNSBs
      ($8749) was similar to the Mdeps ($8960; CI $8555-$9381) and was substantially
      lower than TRDBs ($13,618; CI $12,937-$14,342). CONCLUSIONS: VNSBs achieving
      positive health outcomes (measured by lack of negative events post-implantation)
      tend to have fewer psychiatric co-occurring conditions. Lowered costs post
      implantation with evidence of response to VNS suggest the therapy represents an
      option for carefully screened TRDBs who have failed other therapies. LIMITATIONS:
      Administrative data are missing pharmaceuticals and clinical measures. Data for
      the VNS population were not available pre-implantation for comparison to post
      implantation experience. Cost comparisons are adjusted for missing costs in the
      VNS dataset.

PMID- 22954062
TI  - Cost-effectiveness analysis of rosuvastatin vs generic atorvastatin in Spain.
AB  - OBJECTIVE: The objective of this study was to carry out a long-term cost
      effectiveness analysis of rosuvastatin compared with generic atorvastatin in the
      treatment of patients at high cardiovascular (CV) risk (>= 5% Systematic COronary
      Risk Evaluation [SCORE]) and patients with prior cardiovascular disease (CVD) in
      Spain. METHODS: The efficacy data from the Statin Therapies for Elevated Lipid
      Levels compared Across doses to Rosuvastatin (STELLAR) study were used to
      simulate achievement of low-density lipoprotein cholesterol targets with
      different doses of rosuvastatin and generic atorvastatin for an initial period of
      1 year. A Markov model was used to estimate the number of CV complications,
      quality-adjusted life years (QALYs), and healthcare costs (lipid-lowering
      treatment and CV events) for up to 20 years after initial treatment. The analysis
      was carried out from the perspective of the Spanish National Health System, with
      costs (in year 2010 euros) and effects being discounted at 3% per year. RESULTS:
      Compared with generic atorvastatin, rosuvastatin was cost-effective (cost per
      QALY gained of less than ?30,000) for the primary prevention of CV events in high
      risk patients in most sub-groups analyzed. In patients with prior CVD,
      rosuvastatin was cost-effective in all sub-groups of men and most sub-groups of
      women. Key limitations of this study were the need to extrapolate data from a
      single trial to long-term modeled outcomes and the absence of other treatment
      options in the analysis. CONCLUSIONS: For the treatment of dyslipidemic patients
      with high CV risk, rosuvastatin is more effective than generic atorvastatin in
      terms of survival and quality-of-life adjusted survival, with incremental cost
      effectiveness ratios within the range generally used in Spain, in most sub
      populations defined by various combinations of CV risk factors.

PMID- 22954063
TI  - The inpatient experience and predictors of length of stay for patients
      hospitalized with systolic heart failure: comparison by commercial, Medicaid, and
      Medicare payer type.
AB  - OBJECTIVE: Descriptions of the inpatient experience for patients hospitalized
      with systolic heart failure (HF) are limited and lack a cross-sectional
      representation of the US population. While length of stay (LOS) is a primary
      determinant of resource use and post-discharge events, few models exist for
      estimating LOS. RESEARCH DESIGN AND METHODS: MarketScan((r)) administrative
      claims data from 1/1/2005-6/30/2008 were used to select hospitalized patients
      aged >=18 years with discharge diagnoses for both HF (primary diagnosis) and
      systolic HF (any diagnostic position) without prior HF hospitalization or
      undergoing transplantation. RESULTS: Among 17,597 patients with systolic HF; 4109
      had commercial; 2118 had Medicaid; and 11,370 had Medicare payer type. Medicaid
      patients had longer mean LOS (7.1 days) than commercial (6.3 days) or Medicare
      (6.7 days). In-hospital mortality was highest for patients with Medicaid (2.4%),
      followed by Medicare (1.3%) and commercial (0.6%). Commercial patients were more
      likely to receive inpatient procedures. Renal failure, pressure ulcer,
      malnutrition, a non-circulatory index admission DRG, receipt of a coronary artery
      bypass procedure or cardiac catheterization, or need for mechanical ventilation
      during the index admission were associated with increased LOS; receipt of a
      pacemaker device at index was associated with shorter LOS. LIMITATIONS: Selection
      of patients with systolic HF is limited by completeness and accuracy of medical
      coding, and results may not be generalizable to patients with diastolic HF or to
      international populations. CONCLUSION: Inpatient care, LOS, and in-hospital
      survival differ by payer among patients hospitalized with systolic HF, although
      co-morbidity and inpatient procedures consistently influence LOS across payer
      types. These findings may refine risk stratification, allowing for targeted
      intensive inpatient management and/or aggressive transitional care to improve
      outcomes and increase the efficiency of care.

PMID- 22954064
TI  - Staining tumor cells with biotinylated ACL-I, a lectin isolated from the marine
      sponge, Axinella corrugata.
AB  - Axinella corrugata lectin 1 (ACL-1) was purified from aqueous extracts of the
      marine sponge, Axinella corrugata. ACL-1 strongly agglutinates native rabbit
      erythrocytes. The hemagglutination is inhibited by N-acetyl derivatives,
      particularly N, N', N"-triacetylchitotriose, N-acetyl-D-glucosamine, N-acetyl-D
      mannosamine and N-acetyl-D-galactosamine. We investigated the capacity of
      biotinylated ACL-1 to stain several transformed cell lines including breast (T
      47D, MCF7), colon (HT-29), lung (H460), ovary (OVCAR-3) and bladder (T24). ACL-I
      may bind to both monosaccharides and oligosaccharides of tumor cells, N-acetyl-D
      galactosamine, and N-acetyl-D- glucosamine glycan types. The lectins are useful,
      not only as markers and diagnostic parameters, but also for tissue mapping in
      suspicious neoplasms. In addition, they provide a better understanding of
      neoplasms at the cytological and molecular levels. Furthermore, the use of
      potential metastatic markers such as lectins is crucial for developing successful
      tools for therapy against cancer. We observed that biotinylated ACL-I stains
      tumor cells and may hold potential as a probe for identifying transformed cells
      and for studying glycan structures synthesized by such cells.

PMID- 22954065
TI  - Comparison of blood brain barrier permeability in normal and ovariectomized
      female rats that demonstrate right or left paw preference.
AB  - We explored the relations among paw preference, cerebral asymmetry and
      asymmetrical disruption of blood-brain barrier (BBB) permeability in normal and
      ovariectomized female rats with known paw preference. A high dose of
      pentylenetetrazol was used to disrupt the BBB and induce acute hypertension. To
      determine the areas of macroscopic infarct, samples were stained with 2,3,5
      triphenyltetrazolium chloride. Histological staining techniques were used to show
      the areas of infarct microscopically on paraffin sections. Sixty-two percent of
      the rats demonstrated right paw preference, 24% demonstrated left paw preference
      and 14% were ambidextrous. Areas of infarct, which indicated destruction of the
      BBB, were determined microscopically and macroscopically in rats that
      demonstrated right and left paw preference. We found a relation between
      permeability of the BBB and paw preference. There may be a relation between paw
      preference, cerebral asymmetry and asymmetrical destruction of the BBB in rats.
      Asymmetrical destruction of the BBB in experimental rats was similar to the
      control group, which had asymmetrically disrupted BBB with respect to paw
      preference. Like the control rats, asymmetrical areas of infarct consistent with
      cerebral asymmetry were observed in ovariectomized rats.

PMID- 22954066
TI  - Mixed copper, silver, and gold cyanides, (M(x)M'(1-x))CN: tailoring chain
      structures to influence physical properties.
AB  - Binary mixed-metal variants of the one-dimensional MCN compounds (M = Cu, Ag, and
      Au) have been prepared and characterized using powder X-ray diffraction,
      vibrational spectroscopy, and total neutron diffraction. A solid solution with
      the AgCN structure exists in the (Cu(x)Ag(1-x))CN system over the range (0 <= x
      <= 1). Line phases with compositions (Cu(1/2)Au(1/2))CN, (Cu(7/12)Au(5/12))CN,
      (Cu(2/3)Au(1/3))CN, and (Ag(1/2)Au(1/2))CN, all of which have the AuCN structure,
      are found in the gold-containing systems. Infrared and Raman spectroscopies show
      that complete ordering of the type [M-C=N-M'-N=C-](n) occurs only in
      (Cu(1/2)Au(1/2))CN and (Ag(1/2)Au(1/2))CN. The sense of the cyanide bonding was
      determined by total neutron diffraction to be [Ag-NC-Au-CN-](n) in
      (Ag(1/2)Au(1/2))CN and [Cu-NC-Au-CN-](n) in (Cu(1/2)Au(1/2))CN. In contrast, in
      (Cu(0.50)Ag(0.50))CN, metal ordering is incomplete, and strict alternation of
      metals does not occur. However, there is a distinct preference (85%) for the N
      end of the cyanide ligand to be bonded to copper and for Ag-CN-Cu links to
      predominate. Contrary to expectation, aurophilic bonding does not appear to be
      the controlling factor which leads to (Cu(1/2)Au(1/2))CN and (Ag(1/2)Au(1/2))CN
      adopting the AuCN structure. The diffuse reflectance, photoluminescence, and 1-D
      negative thermal expansion (NTE) behaviors of all three systems are reported and
      compared with those of the parent cyanide compounds. The photophysical properties
      are strongly influenced both by the composition of the individual chains and by
      how such chains pack together. The NTE behavior is also controlled by structure
      type: the gold-containing mixed-metal cyanides with the AuCN structure show the
      smallest contraction along the chain length on heating.

PMID- 22954067
TI  - Child undernutrition in affluent societies: what are we talking about?
AB  - In this paper we set out to explore the prevalence of child undernutrition found
      in community studies in affluent societies, but a preliminary literature review
      revealed that, in the absence of a gold standard method of diagnosis, the
      prevalence largely depends on the measure, threshold and the growth reference
      used, as well as age. We thus go on to explore describe the common clinical
      'syndromes' of child undernutrition: wasting, stunting and failure to thrive
      (weight faltering) and how we have used data from two population-based cohort
      studies, this paper to explore how much these different 'syndromes' overlap and
      the extent to which they reflect true undernutrition. This analysis revealed that
      when more than one definition is applied to the same children, a majority are
      below the lower threshold for only one measure. However, those with both weight
      faltering and low BMI in infancy, go on in later childhood to show growth and
      body composition patterns suggestive of previous undernutrition. In older
      children there is even less overlap and most children with either wasting or low
      fat seem to be simply growing at one extreme of the normal range. We conclude
      that in affluent societies the diagnosis of undernutrition is only robust when it
      relies on a combination of both, that is decline in weight or BMI centile and
      wasting.

PMID- 22954068
TI  - A model for abnormal activity recognition and alert generation system for elderly
      care by hidden conditional random fields using R-transform and generalized
      discriminant analysis features.
AB  - BACKGROUND: The growing population of elderly people living alone increases the
      need for automatic healthcare monitoring systems for elderly care. Automatic
      vision sensor-based systems are increasingly used for human activity recognition
      (HAR) in recent years. This study presents an improved model, tested using
      actors, of a sensor-based HAR system to recognize daily life activities of
      elderly people at home and generate an alert in case of abnormal HAR. SUBJECTS
      AND METHODS: Datasets consisting of six abnormal activities (falling backward,
      falling forward, falling rightward, falling leftward, chest pain, and fainting)
      and four normal activities (walking, rushing, sitting down, and standing up) are
      generated from different view angles (90 degrees , -90 degrees , 45 degrees , -45
      degrees ). Feature extraction and dimensions reduction are performed by R
      transform followed by generalized discriminant analysis (GDA) methods. R
      transform extracts symmetric, scale, and translation-invariant features from the
      sequences of activities. GDA increases the discrimination between different
      classes of highly similar activities. Silhouette sequences are quantified by the
      Linde-Buzo-Gray algorithm and recognized by hidden conditional random fields.
      RESULTS: Experimental results provide an average recognition rate of 94.2% for
      abnormal activities and 92.7% for normal activities. CONCLUSIONS: The recognition
      rate for the highly similar activities from different view angles shows the
      flexibility and efficacy of the proposed abnormal HAR and alert generation system
      for elderly care.

PMID- 22954069
TI  - Willingness of Parkinson's disease patients to participate in research using
      internet-based technology.
AB  - BACKGROUND: Motor impairment and travel time have been shown to be important
      barriers to recruitment for Parkinson's disease (PD) clinical trials. This study
      determined whether use of Internet-based video communication for study visits
      would improve likelihood of participating in PD clinical trials. SUBJECTS AND
      METHODS: University of Utah PD clinic patients were invited to complete a survey
      asking if they would be willing to participate in a hypothetical research study
      under four different scenarios. McNemar's test was used to test the hypothesis
      that remote assessments would improve willingness to participate. RESULTS:
      Willingness to participate was 101/113 (87%) in the standard scenario.
      Willingness to participate was highest (93%; p=0.046) with most visits occurring
      via telemedicine at a local clinic, followed by some visits occurring via
      telemedicine at a local clinic (91%; p=0.157). Willingness to participate was
      lower with some (80%; p=0.008) or most (82%; p=0.071) visits occurring by home
      telemonitoring. CONCLUSIONS: Use of telemedicine may be an acceptable means to
      improve participation in clinical trials. This would need to be confirmed with
      the use of a larger-scale inquiry involving rural populations. Future research
      should assess subject or caregiver comfort and trainability with respect to
      computer-based technology in the home and systems barriers for wider
      implementation of telemedicine in neurology.

PMID- 22954070
TI  - Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with
      syringomyelia.
AB  - BACKGROUND: Understanding the pathogenesis of the chiari-like malformation in the
      Cavalier King Charles Spaniel (CKCS) is incomplete, and current hypotheses do not
      fully explain the development of syringomyelia (SM) in the spinal cords of
      affected dogs. This study investigates an unconventional pathogenetic theory for
      the development of cerebrospinal fluid (CSF) pressure waves in the subarachnoid
      space in CKCS with SM, by analogy with human diseases. In children with
      achondroplasia the shortening of the skull base can lead to a narrowing of the
      jugular foramina (JF) between the cranial base synchondroses. This in turn has
      been reported to cause a congestion of the major venous outflow tracts of the
      skull and consequently to an increase in the intracranial pressure (ICP). Amongst
      brachycephalic dog breeds the CKCS has been identified as having an extremely
      short and wide braincase. A stenosis of the JF and a consequential vascular
      compromise in this opening could contribute to venous hypertension, raising ICP
      and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study,
      JF volumes in CKCSs with and without SM were compared to assess a possible role
      of this pathologic mechanism in the development of SM in this breed. RESULTS:
      Computed tomography (CT) scans of 40 CKCSs > 4 years of age were used to create
      three-dimensional (3D) models of the skull and the JF. Weight matched groups (7
      10 kg) of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without
      SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median
      right JF: 0.0703 cm3; p < 0.0001) when compared with CKCSs with SM (median left
      JF: 0.0382 cm3; median right JF: 0.0434 cm3; p < 0.0001). There was no
      significant difference between the left and right JF within each group. Bland
      Altman analysis revealed excellent reproducibility of all volume measurements.
      CONCLUSION: A stenosis of the JF and consecutive venous congestion may explain
      the aetiology of CSF pressure waves in the subarachnoid space, independent of
      cerebellar herniation, as an additional pathogenetic factor for the development
      of SM in this breed.

PMID- 22954071
TI  - De novo synthesis of the bacterial 2-amino-2,6-dideoxy sugar building blocks D
      fucosamine, D-bacillosamine, and D-xylo-6-deoxy-4-ketohexosamine.
AB  - The cell-surface glycans on bacteria contain many monosaccharides that cannot be
      obtained by isolation from natural sources. Availability of differentially
      protected monosaccharides is therefore often limiting access to potential
      oligosaccharide vaccine antigens. D-Fucosamine, D-bacillosamine, and D-xylo-2,6
      deoxy-4-ketohexosamine building blocks were prepared via a divergent de novo
      synthesis from L-Garner aldehyde. The route relies on a chelation-control
      assisted organometallic addition and an anti-selective dihydroxylation reaction.

PMID- 22954072
TI  - Advancing midwifery: the American College of Nurse-Midwives' documents and
      publications.

PMID- 22954073
TI  - Recent trends in clinicians providing care to pregnant women in the United
      States.
AB  - INTRODUCTION: Health care needs of pregnant women are met by a variety of
      clinicians in a changing policy and practice environment. This study documents
      recent trends in types of clinicians providing care to pregnant women in the
      United States. METHODS: We used a repeat cross-sectional design and data from the
      Integrated Health Interview Series (2000-2009), a nationally representative data
      set, for respondents who reported being pregnant at the time of the survey (N =
      3204). Using longitudinal logistic regression models, we analyzed changes over
      time in pregnant women's reported use of care from 1) obstetrician-gynecologists;
      2) midwives, nurse practitioners (NPs), or physician assistants (PAs); or 3) both
      an obstetrician-gynecologist and a midwife, NP, or PA. RESULTS: The percentage of
      pregnant women who reported seeing an obstetrician-gynecologist (87%) remained
      steady from 2000 through 2009. After controlling for demographic and clinical
      variables, the percentage who reported receiving care from a midwife, NP, or PA
      increased 4% annually (yearly adjusted odds ratio [AOR] 1.04; P < .001),
      indicating a cumulative increase of 48% over the decade. The percentage of
      pregnant women who received care from both an obstetrician-gynecologist and a
      midwife, NP, or PA also increased (AOR 1.027; P < .001), for a cumulative
      increase of 30%. DISCUSSION: The increasing role of midwives, NPs, and PAs in the
      provision of maternity care suggests changes in the perinatal workforce and
      practice models that may promote collaborative care and quality improvement.
      However, better data collection is required to gather detailed information on
      specific provider types, these trends, and their implications.

PMID- 22954074
TI  - Prevalence of low vitamin D levels in an urban midwestern obstetric practice.
AB  - INTRODUCTION: This study describes the prevalence of low vitamin D levels in
      pregnancy in a diverse urban population. METHODS: This was a retrospective chart
      review of 2839 women who gave birth at a Michigan hospital between January 1,
      2008 and December 31, 2009 and had at least 1 vitamin D (25-hydroxyvitamin D
      [25(OH)D]) measurement during their pregnancies. Race/ethnic group, wearing the
      hijab, and season of 25(OH)D sample collection were used in the descriptive
      analysis. RESULTS: Most women (92.5%) in this study had documented insufficient
      levels of 25(OH)D (defined as < 30 mL), and 71.7% of all women had deficient
      levels of 25(OH)D (defined as < 20 ng/mL). Subgroups with the highest percentage
      of women who were vitamin D deficient were: Middle Eastern (91.8%), African
      American (81.6%), and Asian (74.3%). Overall, women who wore the hijab were more
      likely to be deficient (89.5% vs 68.7; P < .0001) and insufficient (98.8% vs
      91.4%; P < .0001) compared with women who did not wear the hijab. DISCUSSION: The
      data demonstrate the high rate of vitamin D deficiency and insufficiency in this
      white and nonwhite urban population in which samples were collected in both
      winter and nonwinter months. The percentage of woman who had 25(OH)D levels below
      30 ng/mL was significantly higher than that reported in the National Health and
      Nutrition Examination Survey III (NHANES III) (92.5% compared to 69%), although
      NHANES did not sample women in northern climates in the winter months. Even using
      new diagnostic definitions for vitamin D deficiency from the Institute of
      Medicine, the proportion of women with vitamin D deficiency and insufficiency was
      40% and 31.6%, respectively. Clinicians caring for women in northern climates as
      well as women who are Middle Eastern, African American, and Asian need to be
      aware of the risk for vitamin D deficiency and the potential health effects for
      the mother and infant.

PMID- 22954075
TI  - Comparison of perception of pregnancy risk of nulliparous women of advanced
      maternal age and younger age.
AB  - INTRODUCTION: Over the last 3 decades, the proportion of women who have delayed
      childbearing into their mid 30s and early 40s has been increasing. Because
      advanced maternal age (AMA) is associated with several adverse maternal, fetal,
      and neonatal outcomes, these pregnancies are considered to be "high risk."
      Research indicates that pregnancy risk perception is an important factor in
      pregnant women's health care use and decision making during pregnancy. The
      objectives of this study were to compare risk perception in pregnant women of AMA
      (aged 35 years or older) with that of younger women and to explore the
      relationship between perception of pregnancy risk and selected variables.
      METHODS: A sample of 159 nulliparous pregnant women (105 aged 20-29 years and 54
      aged 35 years or older) was recruited from a variety of settings in Winnipeg,
      Manitoba, Canada. Women were asked to complete questionnaires to assess
      perception of pregnancy risk, risk knowledge, pregnancy-related anxiety,
      perceived control, health status, and medical risk. RESULTS: Women of AMA had
      higher education levels, were more likely to work during pregnancy, and had
      higher medical risk scores than younger women. Women of AMA perceived higher
      pregnancy risk for both themselves and their fetuses than did younger women. They
      rated their risks of cesarean birth, dying during pregnancy, preterm birth, and
      having a newborn with a birth defect or one needing admission to a neonatal
      intensive care unit higher than those of younger women. There were no significant
      differences between the 2 age groups in pregnancy-related anxiety, knowledge of
      risk, perceived control, and health status. DISCUSSION: Women of AMA have a
      higher perception of pregnancy risk than younger women, regardless of their
      medical risk. This evidence suggests that incorporating discussions of pregnancy
      risk into prenatal care visits may assist pregnant women of AMA to make more
      informed choices, reduce anxiety, and avoid unnecessary interventions.

PMID- 22954076
TI  - Differences in quality of antenatal care provided by midwives to low-risk
      pregnant dutch women in different ethnic groups.
AB  - INTRODUCTION: The objective of this study was to evaluate whether differences
      existed in the adherence to the Dutch national guidelines regarding basic
      antenatal care by Dutch midwives for low-risk women of different ethnic groups.
      METHODS: This was an observational study using data from electronic antenatal
      charts of 7 midwife practices (23 midwives), participating in the Generation R
      Study. The Generation R Study is a multiethnic, population-based, prospective,
      cohort study that is investigating the growth, development, and health of urban
      children from fetal life until young adulthood. The study is conducted in
      Rotterdam, The Netherlands. The antenatal charts of 2093 low-risk pregnant women
      with an expected birthing date in 2002 through 2004 were used to determine the
      mean quality of antenatal care scores for 7 ethnic groups. These scores reflected
      the degree of adherence to the guidelines regarding 10 tests and examinations.
      RESULTS: Few differences between ethnic groups were found in adherence to the
      guidelines that addressed the obstetric-technical quality of antenatal care. This
      finding applied more to nulliparous than to multiparous women. Adherence to
      guidelines was not always better in the antenatal care provided to native Dutch
      multiparous women when compared to other ethnic groups. Midwives adhered well to
      the guidelines regarding most tests. For all women, irrespective of ethnic
      background, hemoglobin was not measured as often as recommended, and this was
      especially the case for Moroccan, Surinamese-Creole, and Dutch-Antillean
      multiparous women. DISCUSSION: The poorer adherence regarding screening for
      hemoglobin needs further investigation, as women with African or Mediterranean
      heritage are more at risk for hemoglobinopathies. However, in general, midwives
      adhered well to the clinical guidelines regarding most tests irrespective of the
      ethnic background of the pregnant women. When differences were present, these
      were not systematically less favorable for non-Dutch pregnant women.

PMID- 22954077
TI  - Diversity in the scope and practice of hospital-based midwives in the
      Netherlands.
AB  - INTRODUCTION: Not all midwives in the Netherlands are independent practitioners.
      One in 4 midwives registered to practice is employed in the hospital setting,
      where 67% of all births occur. There has not yet been an in-depth examination of
      hospital-based midwives' practice in the Netherlands, in the context of care in a
      higher-risk environment. The primary aims of this study were to describe the
      diversity and scope of practice of hospital-based midwives in the Netherlands.
      METHODS: This was an online survey of all hospitals throughout the Netherlands
      with labor/birthing rooms and employing hospital-based midwives. The survey
      covered 5 topic areas: demographic/organizational details, duties,
      responsibilities, experience/additional qualifications, and how the midwife
      functioned within the multidisciplinary hospital team. Descriptive statistics are
      provided. RESULTS: A total of 59 secondary and tertiary level hospitals from a
      possible total of 98 were included for analysis (60% national response rate).
      Forty percent of all births occurring during the study period were managed solely
      by a hospital midwife. The provision of midwifery care in the hospital setting
      was not universal, and where present, hospital-based midwives were not
      necessarily available 24 hours a day or 7 days a week. Hospital-based midwives
      reported a high level of autonomy. DISCUSSION: Currently there is no universal
      provision of midwifery care in the hospital setting in the Netherlands. Where
      there are hospital-based midwives, they appear to manage the majority of births.
      However, there are no nationally agreed-upon standards for midwifery practice in
      the hospital setting, and no agreement exists over minimum requirements relating
      to additional education for midwives in these settings. A national evaluation and
      setting of minimum standards is needed.

PMID- 22954078
TI  - Birth outcomes associated with receipt of group prenatal care among low-income
      Hispanic women.
AB  - INTRODUCTION: Although Hispanic women in the United States have preterm birth and
      low-birth-weight rates comparable to non-Hispanic white women, their rates fall
      short of 2010 Healthy People goals, with variability found across states. This
      study examined the effectiveness of the CenteringPregnancy group prenatal care
      model in reducing preterm birth and low-birth-weight rates for Hispanic women.
      METHODS: Pregnant Hispanic women at less than or equal to 20 weeks, gestation
      initiating prenatal care between January 2008 to July 2009 at 2 Palm Beach
      County, Florida, public health clinics selected either group or traditional
      prenatal care. Data on neonatal birth weight and gestational age were obtained
      through abstraction of Palm Beach County Health Department medical records.
      Records were abstracted for 97% of CenteringPregnancy (n = 150) and 94% of
      traditional care (n = 66) participants. RESULTS: A statistically significant
      difference was found in the percentage of women giving birth to preterm neonates
      (5% group prenatal care vs 13% traditional care; P= .04). There were no
      statistically significant differences in the percentage of women having a low
      birth-weight neonate when group and traditional care participants were compared.
      DISCUSSION: The CenteringPregnancy model holds promise for improving the birth
      outcomes of Hispanic women. Future research should be conducted with larger
      sample sizes to replicate study findings using experimental designs and
      incorporating formal cost-effectiveness analyses.

PMID- 22954079
TI  - Induced abortion in Iran: prevalence, reasons, and consequences.
AB  - INTRODUCTION: The aims of this descriptive study were to determine the prevalence
      of illegal induced abortion among participants, the factors that influence
      decision making to have an abortion, and the health consequences of abortion in
      Iran. METHODS: Women who attended health centers or an antenatal clinic in Iran
      were interviewed to complete a questionnaire. RESULTS: Among the 2705
      participants, 17% had experienced at least 1 illegal induced abortion. Education
      level, family income, religion, ethnicity, number of children, and age at
      marriage are associated with having an induced abortion. One-third of abortions
      (33%) were performed by nonmedical providers. The desire to stop or postpone
      childbearing and family economic problems were the most common reasons for having
      an abortion. Most women (84%) experienced a complication of abortion that
      required hospitalization. DISCUSSION: Strategies to prevent abortion
      complications are needed and could include training midwives and general
      physicians to perform abortions and promoting the availability of post-abortion
      care.

PMID- 22954080
TI  - Falling out: authoritative knowledge and women's experiences with pelvic organ
      prolapse.
AB  - INTRODUCTION: Despite the high prevalence of pelvic organ prolapse, many women
      suffer in silence, lacking the language and opportunity to describe their
      condition. There are limited descriptions of women's experiences with pelvic
      organ prolapse in the literature. This qualitative study addressed the knowledge
      and experience of women with pelvic organ prolapse. METHODS: Semistructured
      interviews were conducted with 13 women who had been previously diagnosed with
      pelvic organ prolapse. Transcripts of the interviews were reviewed and coded
      using a process of content analysis compared against the framework of
      authoritative knowledge, developed by Brigitte Jordan. RESULTS: By applying the
      concept of authoritative knowledge, we identified 3 themes of how women construct
      understanding about pelvic organ prolapse and how they demonstrate deference to
      the authoritative knowledge of medical providers. First, we found through women's
      narratives that authoritative knowledge was held by the health care provider and
      is considered consequential and legitimate by all participants. Second, women
      reported that the health care provider's authoritative knowledge was valued over
      personal, experiential knowledge. Finally, women described how they work with
      their health care providers to create a system of authoritative knowledge as they
      seek treatment for or discuss their condition. Throughout the narratives, women's
      experiences are not legitimized by the women or the medical community,
      perpetuating the "hidden" nature of these conditions. DISCUSSION: This analysis
      provides qualitative evidence of Jordan's authoritative knowledge: women and
      health care providers contribute to dimensions of authoritative knowledge
      surrounding pelvic organ prolapse. Despite what women experience, the health care
      provider's definition and understanding of pelvic organ prolapse is seen as
      legitimate and consequential. Because of their construction of their condition,
      and the power dynamic at play, women are silenced, and their expertise about
      their bodies is delegitimized, limiting their active participation in seeking
      care for this condition.

PMID- 22954081
TI  - Behavior change following implementation of home-based life-saving skills in
      Liberia, West Africa.
AB  - INTRODUCTION: Home-Based Life-Saving Skills (HBLSS) has been fully integrated
      into Liberia's long-term plan to decrease maternal and newborn mortality and
      morbidity, coordinated through the Ministry of Health and Social Welfare. The
      objective of this article is to disseminate evaluation data from project
      monitoring and documentation on translation of knowledge and skills obtained
      through HBLSS into behavior change at the community level. METHODS: One year
      after completion of HBLSS training, complication audits were conducted with 434
      postpartum women in 1 rural county in Liberia. RESULTS: Sixty-two percent (n =
      269) of the women were attended during birth by an HBLSS-trained traditional
      midwife or family member, while 38% (n = 165) were attended by a traditional
      midwife or family member who did not receive HBLSS training. Home-Based Life
      Saving Skills-trained birth attendants performed significantly more first actions
      (life-saving actions taught to be performed after every birth) than the
      attendants not HBLSS trained. Fourteen percent of our sample (n = 62) reported
      too much bleeding following the birth. Of these women, approximately half (n =
      29) were attended by an HBLSS-trained traditional midwife or family member. There
      was a significant difference in secondary actions (those actions taught to be
      performed when a woman experiences too much bleeding following childbirth) that
      were reported to have been performed by HBLSS-trained attendants (mean 5.26,
      standard deviation [SD] 1.88) and untrained attendants (mean 2.73, SD 1.97; P <
      .0001). DISCUSSION: Our findings suggest that HBLSS knowledge is being
      transferred into behavior change and used at the community level by traditional
      midwives and family members.

PMID- 22954083
TI  - Large population-based study finds that elective induction at term reduces
      perinatal mortality.

PMID- 22954082
TI  - Current resources for evidence-based practice, September/October 2012.

PMID- 22954084
TI  - Women health care providers serving in the military report more psychological
      stress than is reported by men.

PMID- 22954085
TI  - Intrauterine devices provide safe and effective contraception following
      unprotected intercourse and beyond.

PMID- 22954087
TI  - Midwives and abortion care: a model for achieving competency.

PMID- 22954089
TI  - Midwives and abortion care: a model for achieving competency.

PMID- 22954092
TI  - Supporting healthy and normal physiologic childbirth: a consensus statement by
      the American College of Nurse-Midwives, Midwives Alliance of North America, and
      the National Association of Certified Professional Midwives.

PMID- 22954101
TI  - Reduction-sensitive tioguanine prodrug micelles.
AB  - Colloidal drug and prodrug conjugates have unique targeting characteristics for
      tumor vasculature from the blood and for the lymphatics draining a tissue
      injection site. Tioguanine and tioguanine-generating prodrugs have been
      investigated as anticancer and immunosuppressive agents, including use in cancer
      immunotherapy. Recently we developed block copolymers of poly(ethylene glycol)-bl
      poly(propylene sulfide) that self-assemble in aqueous solutions to form micellar
      structures. Since the polymers carry a free terminal thiol group resulting from
      the ring-opening polymerization of the propylene sulfide monomer, we sought to
      prepare prodrug block copolymers with tioguanine linked by a reduction-sensitive
      disulfide bond. The synthesis involved a disulfide exchange between the oxidized
      form of tioguanine and the polymer. Spectroscopic data is presented to support
      the proposed reaction. The polymers self-assembled when dispersed in water to
      form tioguanine prodrug micelles with a size range between 18 and 40 nm that
      released tioguanine in response to cysteine and serum as shown spectroscopically.
      In comparison with a poly(ethylene glycol) prodrug polymer, we show that the rate
      of tioguanine release can be controlled by changing the poly(propylene sulfide)
      block length and that the tioguanine remains bioactive with cultured cells.

PMID- 22954102
TI  - MIRU-VNTR analysis of the Mycobacterium tuberculosis isolates from three
      provinces of Iran.
AB  - BACKGROUND: Iran borders 2 high-burden tuberculosis (TB) countries to the east,
      and has the highest rates of TB in one of its eastern provinces. Limited
      information is available on the genetic diversity and transmission dynamics of
      Mycobacterium tuberculosis (MTB) in Iran. To examine the genetic diversity and
      transmission dynamics of MTB strains we genotyped a collection of isolates from
      different parts of Iran. METHODS: Standard 15-locus variable number tandem repeat
      (VNTR) typing was applied to genotype 121 MTB clinical isolates collected from 3
      provinces of Iran, including Tehran (the capital of Iran), Sistan-Baluchestan
      (southeast province of Iran, with the highest rate of TB), and Kermanshah
      (western part of Iran with high TB/human immunodeficiency virus cases).
      Antibiotic susceptibility for all isolates was determined using the proportion
      method. RESULTS: Sixty-six distinct mycobacterial interspersed repetitive unit
      (MIRU)-VNTR patterns were detected among 121 isolates. Seventy-five strains
      grouped into 20 clusters, and 46 isolates were unique. The genetic diversity of
      strains from Sistan-Baluchestan was higher than that in the other provinces. All
      isolates from Tehran or Kermanshah that grouped into clusters shared identical
      patterns with Sistan-Baluchestan. The Hunter-Gaston discriminatory index (HGDI)
      was 0.972, indicating a high power of discrimination for MIRU-VNTR typing. The
      MIRU 16 and ETRA loci were designated as highly discriminative. The rates of
      monoresistance and multidrug resistance were 9.9% and 2.4%, respectively.
      CONCLUSIONS: MIRU-VNTR typing revealed high genetic diversity and suggests the
      possibility of transmission from Sistan-Baluchestan to other provinces of Iran.
      This method has potential for genetic analysis and for studying the transmission
      routes of TB.

PMID- 22954103
TI  - A halomethane thermochemical network from iPEPICO experiments and quantum
      chemical calculations.
AB  - Internal energy selected halomethane cations CH(3)Cl(+), CH(2)Cl(2)(+),
      CHCl(3)(+), CH(3)F(+), CH(2)F(2)(+), CHClF(2)(+), and CBrClF(2)(+) were prepared
      by vacuum ultraviolet photoionization, and their lowest energy dissociation
      channel studied using imaging photoelectron photoion coincidence spectroscopy
      (iPEPICO). This channel involves hydrogen atom loss for CH(3)F(+), CH(2)F(2)(+),
      and CH(3)Cl(+), chlorine atom loss for CH(2)Cl(2)(+), CHCl(3)(+), and
      CHClF(2)(+), and bromine atom loss for CBrClF(2)(+). Accurate 0 K appearance
      energies, in conjunction with ab initio isodesmic and halogen exchange reaction
      energies, establish a thermochemical network, which is optimized to update and
      confirm the enthalpies of formation of the sample molecules and their
      dissociative photoionization products. The ground electronic states of
      CHCl(3)(+), CHClF(2)(+), and CBrClF(2)(+) do not confirm to the deep well
      assumption, and the experimental breakdown curve deviates from the deep-well
      model at low energies. Breakdown curve analysis of such shallow well systems
      supplies a satisfactorily succinct route to the adiabatic ionization energy of
      the parent molecule, particularly if the threshold photoelectron spectrum is not
      resolved and a purely computational route is unfeasible. The ionization energies
      have been found to be 11.47 +/- 0.01 eV, 12.30 +/- 0.02 eV, and 11.23 +/- 0.03 eV
      for CHCl(3), CHClF(2), and CBrClF(2), respectively. The updated 0 K enthalpies of
      formation, Delta(f)H(o)(0K)(g) for the ions CH(2)F(+), CHF(2)(+), CHCl(2)(+),
      CCl(3)(+), CCl(2)F(+), and CClF(2)(+) have been derived to be 844.4 +/- 2.1,
      601.6 +/- 2.7, 890.3 +/- 2.2, 849.8 +/- 3.2, 701.2 +/- 3.3, and 552.2 +/- 3.4 kJ
      mol(-1), respectively. The Delta(f)H(o)(0K)(g) values for the neutrals CCl(4),
      CBrClF(2), CClF(3), CCl(2)F(2), and CCl(3)F and have been determined to be -94.0
      +/- 3.2, -446.6 +/- 2.7, -702.1 +/- 3.5, -487.8 +/- 3.4, and -285.2 +/- 3.2 kJ
      mol(-1), respectively.

PMID- 22954104
TI  - Probing biochemical mechanisms of action of muscarinic M3 receptor antagonists
      with label-free whole cell assays.
AB  - Binding kinetics of drugs is increasingly recognized to be important for their in
      vivo efficacy and safety profiles. However, little is known about the effect of
      drug binding kinetics on receptor signaling in native cells. Here we used label
      free whole cell dynamic mass redistribution (DMR) assays under persistent and
      duration-controlled stimulation conditions to investigate the influence of the
      binding kinetics of four antagonists on the signaling of endogenous muscarinic M3
      receptor in native HT-29 cells. Results showed that DMR assays under different
      conditions differentiated the biochemical mechanisms of action of distinct M3
      antagonists. When co-stimulated with acetylcholine, tiotropium, a relatively slow
      binding antagonist, was found to selectively block the late signaling of the
      receptor, suggesting that acetylcholine attains its binding equilibrium faster
      than tiotropium does, thereby still being able to initiate its rapid response
      until the antagonist draws up and fully blocks the signaling. Furthermore, DMR
      assays under microfluidics allowed estimation of the residence times of these
      antagonists acting at the receptor in native cells, which were found to be the
      determining factor for the blockage efficiency of M3 receptor signaling under
      duration-controlled conditions. This study demonstrates that DMR assays can be
      used to elucidate the functional consequence of kinetics-driven antagonist
      occupancy in native cells.

PMID- 22954105
TI  - Rapid access to compound libraries through flow technology: fully automated
      synthesis of a 3-aminoindolizine library via orthogonal diversification.
AB  - A novel methodology for the synthesis of druglike heterocycle libraries has been
      developed through the use of flow reactor technology. The strategy employs
      orthogonal modification of a heterocyclic core, which is generated in situ, and
      was used to construct both a 25-membered library of druglike 3-aminoindolizines,
      and selected examples of a 100-member virtual library. This general protocol
      allows a broad range of acylation, alkylation and sulfonamidation reactions to be
      performed in conjunction with a tandem Sonogashira coupling/cycloisomerization
      sequence. All three synthetic steps were conducted under full automation in the
      flow reactor, with no handling or isolation of intermediates, to afford the
      desired products in good yields. This fully automated, multistep flow approach
      opens the way to highly efficient generation of druglike heterocyclic systems as
      part of a lead discovery strategy or within a lead optimization program. 

PMID- 22954106
TI  - Myo9B is associated with an increased risk of Barrett's esophagus and esophageal
      adenocarcinoma.
AB  - BACKGROUND: Reflux esophagitis (RE) and Barrett's esophagus (BE) are predisposing
      factors for development of esophageal adenocarcinoma (EAC), the solid tumor with
      the fastest rising incidence in the Western world. This RE-BE-EAC cascade
      involves multiple host factors and consequently multiple genes. Polymorphisms in
      the 3' region of myosin IXB (Myo9B) are associated with chronic inflammatory
      gastrointestinal disorders like celiac disease and ulcerative colitis, assuming
      that variation in Myo9B influences the intestinal permeability. AIM: To determine
      esophageal expression and the genetic variation of the Myo9B gene in the RE-BE
      EAC cascade. METHODS: DNA from 886 Caucasian participants (198 non-reflux
      controls, 305 RE, 254 BE, 129 EAC) was collected for the determination of the
      Myo9B gene polymorphism (rs2305764). Esophageal Myo9B expression was determined
      on biopsies from normal, RE, BE and EAC epithelium. RESULTS: Genotype G/G was
      more common in BE (p = 0.032) and EAC (p = 0.046), but not in RE (p = 0.126)
      compared with the control group. Cytoplasmic Myo9B expression was determined in
      RE, BE and EAC, but most prominent in epithelial cells of BE and EAC.
      CONCLUSIONS: Genetic variation of Myo9B may play a role in the etiology of BE and
      EAC by increasing the permeability of the epithelial barrier.

PMID- 22954107
TI  - Ruptured intracranial tubercular infectious aneurysm secondary to a tuberculoma
      and its endovascular management.
AB  - Tuberculosis remains to be an endemic infectious disease in developing countries.
      With the increasing incidence of HIV and AIDS, there is further increase in the
      incidence of tuberculosis. Although CNS involvement by tuberculosis is seen in
      all age groups, there is a predilection for younger patients. Central nervous
      system tuberculosis may present as tuberculoma, cerebral abscess or tuberculous
      meningitis (TBM). Vasculitis secondary to TBM can cause infarcts and rarely
      aneurysm formation. In TBM there is a thick, gelatinous exudate around the
      sylvian fissures, basal cisterns. There is a border zone reaction occurring in
      the surrounding brain tissue. Inflammatory changes occur in the vessel wall of
      the arteries bathed in the exudate leading to narrowing of the lumen or occlusion
      by thrombus formation. The vessels at the base of the brain are most severely
      affected, including the internal carotid artery, proximal middle cerebral artery
      and perforating vessels of the basal ganglion. In these cases, the infection
      probably spreads from the adventitia towards the internal elastic lamina,
      weakening the vessel wall, with subsequent formation of an infectious aneurysm.
      Intracranial tuberculomas are space-occupying masses of granulomatous tissue that
      result from haematogenous spread from a distant focus of tuberculous infection.
      In endemic regions, tuberculomas account for as many as 50% of all intracranial
      space-occupying lesions. Inflammation in the vessels surrounding the tuberculoma
      may lead to formation of aneurysms. This case report illustrates an unusual case
      of intracranial tuberculomas complicated by intralesional haemorrhage due to an
      infective tubercular aneurysm in its vicinity. The endovascular treatment of
      these infectious aneurysms is safe, effective and durable. To the best of our
      knowledge, this is the first case report of a tuberculoma having intracranial
      haemorrhage on anti-tubercular treatment due to an infectious aneurysm developing
      in an artery in the vicinity of the tuberculoma and managed end.

PMID- 22954108
TI  - Mind your language: conveying the results of clinical trials of cardiovascular
      therapies.

PMID- 22954109
TI  - Molecular engineering to control the magnetic interaction between single-chain
      magnets assembled in a two-dimensional network.
AB  - Two two-dimensional (2D) systems having the formula
      [{Fe(III)(dmbpy)(CN)(4)}(2)Co(II)L](n) [L = pyetNO (1), tvpNO (2)] and consisting
      of single-chain magnets connected through organic ligands (L) have been prepared,
      and their magnetic properties have been investigated. The overall magnetic
      behavior depends on the capacity of the organic pillars to transmit long-range
      magnetic interactions. 1 is the first example of a 2D compound exhibiting double
      relaxation of the magnetization, whereas 2 behaves as a metamagnet.

PMID- 22954110
TI  - Construction of chimeric E3s expression plasmids targeting oncoprotein ras.
AB  - OBJECTIVE: To construct certain chimeric E3s expression plasmids targetting
      oncoprotein Ras by harnessing the theory of protein knockdown. METHODS: We chose
      the binding domain of Raf-1, PI3K, RalGDS, and the function domain of F-Box as
      well as the U-Box to construct the plasmids. Then used the double enzyme, PCR,
      and sequence to test the validity and integrity of the cloned nucleotide
      fragments. The expression efficiency of the plasmids in eukaryotic cells was
      detected by Western blot analysis. RESULTS: Five of 6 plasmids in this study
      expressed the corresponding fusion proteins in HEK293T cells, and (RBD+CRD)(Raf
      1)- U-Box-pcDNA3.1 can knocked down the protein level of Ras in PANC-1 cells.
      CONCLUSIONS: We successfully constructed the chimeric E3 expression plasmids,
      which provides a solid basis for further research on protein knockdown.

PMID- 22954111
TI  - Effect of LY294002 on adriamycin-induced epithelial-mesenchymal transition in
      human breast carcinoma cells.
AB  - OBJECTIVE: To study the effect of LY294002 on the adriamycin- induced epithelial
      mesenchymal transition in human breast carcinoma cells. METHODS: Human breast
      carcinoma cells MCF-7 was cultured in vitro and then exposed to adriamycin with
      or without LY294002. The protein expression levels of Akt, phosphorylated-Akt (p
      Akt), Snail, and E-cadherin was detected by Western blot analysis. The mRNA
      expressions of Snail and E-cadherin were determined by RT-PCR. RESULTS:
      Adriamycin significantly increased the protein expression of Snail and depressed
      the protein expression of E-cadherin (P<0.05). The pre-treatment with LY294002
      significantly reversed the changes of activities and levels of the above proteins
      (P<0.05). CONCLUSION: LY294002 could reverse the adriamycin-induced epithelial
      mesenchymal transition in human breast carcinoma cells by regulating the
      expressions of Snail and E-cadherin through suppressing PI3K/Akt signaling
      pathway.

PMID- 22954112
TI  - Effects of propofol and dizocilpine maleate on the cognitive abilities and the
      hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy.
AB  - OBJECTIVE: To explore the effects of propofol and dizocilpine maleate (MK-801) on
      the cognitive abilities the hyperphosphorylation of Tau protein of rats after the
      electroconvulsive therapy. METHODS: Two intervention factors including
      electroconvulsive shock therapy (ECT) (two levels: not applied and one treatment
      course) and drug intervention (three levels: intravenous saline,intravenous MK
      801, and intravenous propofol). The morris water maze test started within 1 day
      after ECT to evaluate the learning-memory. The glutamate level in the hippocampus
      of rats was determined by high-performance liquid chromatography. The Tau protein
      that includes Tau5 (total Tau protein), PHF-1 (pSer(396/404)), AT8
      (pSer(199/202)), and 12E8 (pSer(262)) in the hippocampus of rats was determined
      using Western blotting. RESULTS: Propofol, MK-801, and ECT could induce the
      impairment of learning-memory in depressed rats. The electroconvulsive shock
      significantly up-regulated the glutamate level, which was reduces by the
      propofol. The ECT up-regulated the hyperphosphorylation of Tau protein in the
      hippocampus of depressed rats, which was reduced by propofol and MK-801.
      CONCLUSION: Both propofol and MK-801 could protect against the impairment of
      learning-memory and reduce the hyperphosphorylation of Tau protein induced by ECT
      in depressed rats.

PMID- 22954113
TI  - Effect and mechanism of zoledronate on prevention of collapse in osteonecrosis of
      the femoral head.
AB  - OBJECTIVE: To observe the effect and mechanism of zoledronate on prevention of
      collapse in an animal model of osteonecrosis. METHODS: Ischemic osteonecrosis was
      surgically induced in 16 SD rats (which were further divided into zoledronate
      group and placebo group); another 8 rats were used as sham surgery group (n=8).
      The animals were killed 5 weeks after surgery. Radiographic, Micro-CT,
      histological, and immunohistochemical assessments were performed. RESULTS:
      Radiographic assessment showed better preservation of the femoral head shape in
      the zoledronate group than in the placebo group but not significantly different
      from the sham surgery group. Micro-CT assessment showed higher total volume, bone
      volume, and total mineralized content in the zoledronate group(all P0.05).
      Compared with the placebo group, the zoledronate group had reduced osteoclast and
      osteoblast activity, as confirmed by histological examinations. CONCLUSION:
      Zoledronate can decrease the femoral head deformity by reducing the osteoclast
      activity while suppressing new bone and vessels formation in a rat model of
      traumatic osteonecrosis, and therefore may delay the collapse of femoral head.

PMID- 22954114
TI  - Efficacy of homemade hemostatics of injected gelatin matrix for immediately
      treating blunt hepatic trauma in canine model without additional pressure.
AB  - OBJECTIVE: To explore the efficacy of homemade hemostatics of injected gelatin
      matrix (HIGM) for immediately treating blunt hepatic trauma in canine model
      without additional pressure. METHODS: A total of 27 commercial hybrid dogs
      underwent celiotomy to establish hepatic trauma model after general anesthesia.
      The dogs were prospectively randomized into 3 groups: the treatment group (n=9,
      with the direct application of homemade hemostat), the positive control group
      (n=9, with thrombin solution), and the negative control group (n=9, with 0.9%
      normal saline). Time to hemostasis and intra-abdominal blood loss were recorded,
      and heart rate (HR), mean arterial pressure (MAP), and hematological parameters
      were compared among these three groups. Gross examinations were performed 30
      minutes after surgery. RESULTS: Significantly shorter time to hemostasis [(1.20+/
      0.33) min] and less blood loss [(47.22+/-8.61) ml] were observed in the treatment
      group than in control groups (P 0.05). No cases of bleeding occurred in any
      animals in the treatment group, and no signs of infection and adhesion formation
      were evident due to exposure to HIGM. Two cases in the positive control group
      (22.22%) were found to have rebleeding. All animals in the negative control group
      experienced visible bleeding. CONCLUSION: HIGM is effective for controlling
      bleeding after hepatic trauma without the additional compression, and therefore
      may be valuable in field surgery.

PMID- 22954115
TI  - Establishment of a new method to induce the differentiation of embryonic
      pancreatic cells into mature endocrine cells.
AB  - OBJECTIVE: To establish a new culture method to induce the differentiation of
      embryonic pancreatic cells into mature endocrine cells. METHODS: Mouse embryos at
      day 12.5 were used and embryonic pancreata were isolated. The isolated embryonic
      pancreata were cultured on the filter for 7 days, which floated in the dish
      containing medium. During culture, the expression of pancreas duodenum homeobox-1
      (PDX-1), a pancreatic stem cell marker, was examined at day 1. The expression of
      neurogenin 3 (Ngn3), a pancreatic progenitor cell marker, was examined at day 3.
      The expressions of endocrine and exocrine markers, insulin, glucagon, and
      carboxypeptidase (CPA) were examined at day 7 by immunohistochemistry. The
      kinetics of pancreatic marker expression during culture was assayed by real-time
      PCR. RESULTS: Many pancreatic stem cells still existed in embryonic pancreata
      cultured for 1 day; meanwhile, these pancreatic stem cells proliferated in high
      rate. A large amount of pancreatic progenitor cells were found in embryonic
      pancreata cultured for 3 days.Pancreatic stem/progenitor cells differentiated
      into mature endocrine and exocrine cells in embryonic pancreata after having been
      cultured for 7 days. Furthermore, the expression pattern of pancreatic marker is
      consistent with that in vivo. CONCLUSION: We successfully established a new
      culture method, with which embryonic pancreatic cells can efficiently
      differentiate into mature endocrine cell.

PMID- 22954116
TI  - Effect of adenovirus-mediated basic fibroblast growth factor gene transfer in
      vivo on oligodendrocyte cell numbers throughout ventrolateral white matter
      following spinal cord injury in rats.
AB  - OBJECTIVE: To study the effect of adenovirus-mediated basic fibroblast growth
      factor(FGF-2) gene transfer in vivo on oligodendrocyte cell numbers throughout
      ventrolateral white matter following spinal cord injury in rats. METHODS: Thirty
      two adult female Sprague Dawley rats were injured with the Infinite Horizon
      Impactor, and then were randomly assigned to four groups: FGF-2-Adts high-titer
      group (1.27x10(7) pfu/rat), FGF-2-Adts intermediate-titre group (6.37x10(6)
      pfu/rat), FGF-2-Adts low-titer group (3.18 x 10(6) pfu/rat), and green
      fluorescent protein (GFP)-Adts group (5.9x10(7) pfu/rat). The transgenic
      expression in vivo was detected with fluorescence microscopy. The locomotor
      function of the hindlimbs of rats was evaluated using Rivlin plate. Slides
      mounted with tissue sections were processed for immunohistochemical detection and
      quantification of oligodendrocytes (CC1(+)) in the ventral lateral funiculi (VLF)
      of injured spinal cords. RESULTS: One week after spinal cord injury, GFP showed
      that many cells had expressed objective gene in vivo and the angles of the
      occlusal plane of rats in FGF-2 groups were significantly higher than in GFP-Adts
      group. Also, there was a significant difference among the FGF-2-Adts treatment
      groups for the volume of gray matter sparing. However, there were no significant
      differences for total white matter sparing. Stereological quantification of total
      CC1(+) cell numbers in the spared VLF showed a significant reduction in numbers
      with GFP controls compared to all other groups 4 weeks after injury. In contrast,
      the FGF-2 Adts intermediate-titer group had significantly more CC1(+) cells when
      compared to both the FGF-2-Adts high- and low-titer groups. CONCLUSION:
      Adenovirus-mediated FGF-2 gene transfer can promote the functional recovery of
      the injured spinal cord by enhancing the proliferation and/or differentiation of
      oligodendrocytes.

PMID- 22954117
TI  - Effect of 3.6-mT sinusoidal electromagnetic fields on proliferation and
      differentiation of osteoblasts in vitro.
AB  - OBJECTIVE: To investigated the effect of 50-Hz 3.6-mT sinusoidal electromagnetic
      fields (SEMFs) on the proliferation and differentiation of osteoblasts in vitro.
      METHODS: The newborn rat calvarial osteoblasts were isolated by enzyme digestion
      and randomly divided into 6 groups after one passage. The treatment groups under
      50-Hz 3.6-mT SEMFs and controls without SEMFs treatment. The cells were exposed
      in the SEMFs for 0.5 h, 1.0 h, 1.5 h, 2.0 h, and 2.5 h. They were observed under
      the contrast phase microscope each day. The calcified nodules were stained by
      alizarin red. The SEMFs were arranged in spiral appearance after 3 to 5 days.
      RESULTS: The SEMFs showed characteristic distribution 3 to 5 days after SEMFs
      treatment. On the 9(th) day after treatment, the activity of alkaline phosphatase
      (ALP) significantly increased in the 0.5-h group, whereas the ALP histochemical
      straining results and the area of calcified nodules were consistent with ALP
      activity. In the 48-h and 96-h groups, the genetic expression levels of
      osteoprotegerin and collagen-1 were significantly higher than that in the control
      group; particularly, the mRNA expression increased in the 0.5-h group.
      CONCLUSION: The SEMFs at 50-Hz 3.6-mT could suppress the proliferation of
      osteoblasts maturation but stimulate the differentiation and maturation of
      osteoblasts in vitro.

PMID- 22954118
TI  - Correlations of podocyte injury with glucose regulated protein 78 expression and
      proteinuria in patients with diabetic nephropathy.
AB  - OBJECTIVE: To explore the podocyte injury in patients with diabetic nephropathy
      (DN) and analyze its relationship with glucose regulated protein 78 (GRP78) and
      proteinuria. METHODS: The clinical data of 48 patients diagnosed as DN by renal
      biopsy were reviewed. All patients were divided into two groups according to
      proteinuria (>3.5 g/d, n=31 and 3.5 g/d, n=17). The density of podocytes was
      illustrated by immunohistochemistry staining of Wilms tumor-1 (WT-1), and the
      immunofluorescence double-staining results of synaptopodin and GRP78 in podocytes
      were detected. RESULTS: The podocyte dentistry of urine protein > 3.5 g/d group
      was significantly lower than that of urine protein>3.5 g/d group urine
      protein<3.5 g/d group(P=0.003), and it was negatively correlated with proteinuria
      (P=0.005). The expressions of synaptopodin and GRP78 in podocytes were also
      negatively correlated with proteinuria (P=0.004 and P=0.001). CONCLUSION: The
      podocyte injury is aggravated with increased proteinuria in DN patients, along
      with the decrease of the adaptive ability of endoplasmic reticulum to stress.

PMID- 22954119
TI  - Role of contrast-enhanced ultrasound in the differentiation of high- and low
      grade urothelial carcinoma.
AB  - OBJECTIVE: To investigate the role of contrast-enhanced ultrasound in the
      differential diagnosis of high- and low-grade urothelial carcinoma. METHODS: The
      radiological data of 96 patients with urothelial carcinomas who had undergone
      gray-scale contrast-enhanced ultrasound from August 2010 to April 2011 were
      analyzed retrospectively. Pathological examination demonstrated that the tumors
      were high-grade in 55 cases (high-grade group) and low-grade in 41 cases (low
      grade group). The dynamic images were analyzed by time-intensity curve, and the
      arrival time (AT), peak intensity (PI), time to peak (TTP), and washout time (WT)
      were measured. The enhancement patterns of different urothelial carcinomas were
      analyzed. RESULTS: Both PI (P=0.005) and WT (P=0.002) were significantly higher
      in high-grade group than in low-grade group, whereas AT (P=0.374) and TTP
      (P=0.386) showed no significant difference between these two groups. In the high
      grade group, 47 cases (85.5%) were identified as fast wash-in and slow wash-out;
      in the low-grade group, 35 (85.4%) were identified as fast wash-in and fast wash
      out. When the enhancement pattern was used as a diagnostic indicator for
      differentiating urothelial carcinomas, the sensitivity, specificity, accuracy,
      positive predictive value, and negative predictive value were 85.5%, 90.2%,
      87.5%, 92.2%, and 82.2% for high-grade tumor and 85.4%, 90.9%, 88.5%, 87.5%, and
      89.3% for low-grade tumor. CONCLUSIONS: Different grade urothelial carcinomas
      show different enhancement finding on contrast-enhanced ultrasound. The
      enhancement pattern can serve as an important diagnostic indicator.

PMID- 22954120
TI  - Prognostic value of ultra-sensitive pregnancy associated plasma protein-A in
      patients with acute coronary syndrome.
AB  - OBJECTIVE: To investigate the prognostic value of ultra-sensitive pregnancy
      associated plasma protein-A (PAPP-A) level in the early phase of acute coronary
      syndrome (ACS) attack. METHODS: Patients diagnosed as ACS were enrolled and the
      level of circulatory PAPP-A was measured within 12 hours after ACS attack. The
      patients were followed at the time of 1st, 6th, and 12th months post-ACS attack
      in order to observe the incidence of the cardiovascular adverse events. According
      to the highest quintile, the patients were divided into 2 groups: high level
      (>=26.08 MUg/L) group and low level (<26.08 MUg/L) group, to evaluate the
      association between the level of PAPP-A and the incidence of the cardiovascular
      events. RESULTS: Compared with the low level group, the incidence of the
      composite outcome is significantly increased in the high level group, and the
      values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively
      (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR
      were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis
      demonstrates that PAPP-A was an independent risk factor for the cardiovascular
      adverse events in the early, median, and late phase of ACS (P<0.05). CONCLUSION:
      In the early phase of ACS attack, the elevation of PAPP-A is an independent risk
      factor for the occurrence of cardiovascular adverse events.

PMID- 22954121
TI  - Effectiveness of pimecrolimus cream for women patients with sensitive skin and
      its underlying mechanism.
AB  - OBJECTIVE: To investigate the effectiveness of pimecrolimus cream 1% for
      sensitive skin in adult women and its underlying mechanisms. METHODS: The changes
      of subjective symptoms and signs were evaluated before and after the application
      of pimecrolimus cream 1% based on the severity of pruritus (SP) and severity of
      burning sensation (SB) scores, and on a basic syntax and molecular substrate
      (molecular psychophysics) of nociception and proprioception established by
      temperature-sensitive transient receptor potential (TRP) channels. RESULTS: The
      SP and SB scores were significantly decreased in 32 patients with sensitive skin
      after using topical pimecrolimus cream 1% (P<0.05). Twenty (62.5%) patients
      showed positive capsaicin-like response (i.e. burning with consequent rapid
      amelioration of pruritus or burning sensation) and 6 (18.8%) showed positive
      camphor-like response (i.e. warming with consequent rapid amelioration of
      pruritus) on application sites after using the topical pimecrolimus cream 1%, and
      6 (18.8%) showed negative capsaicin-like response and/or negative camphor-like
      response. CONCLUSIONS: Pimecrolimus may rapidly inhibit or alleviate itch or
      burning sensation of patients with sensitive skin. The therapeutic effect of
      pimecrolimus is relevant to the mechanisms that activate or sensitize transient
      receptor potential vanilloid 1 (TRPV1) and desensitizes TRPV1 in the skin sensory
      afferents.

PMID- 22954122
TI  - Effect of peroxisome proliferator activated receptor gamma agonist on angiotensin
      converting enzyme 2 mRNA expression in monocyte-derived macrophages of essential
      hypertensive patients.
AB  - OBJECTIVE: To study the effect of peroxisome proliferator activated receptor
      gamma (PPAR-gamma) agonist on the angiotensin converting enzyme 2 (ACE2) mRNA
      expression in monocyte-derived macrophages of essential hypertensive patients.
      METHODS: Totally 57 essential hypertensive patients were randomly divided into
      three groups: conventional treatment group (n=18), telmisartan group (n=19), and
      benazepril group (n=20); 20 patients with normal blood pressure were also
      selected as the control group. Monocyte-derived macrophages were isolated from
      blood samples of patients in all four groups. The expression of ACE2 mRNA in
      monocyte-derived macrophages was detected by RT-PCR before treatment and 4 and 12
      weeks after treatment. RESULTS: Four and 12 weeks after treatment, the systolic
      pressure and diastolic pressure of telmisartan group and benazepril group were
      significantly lower than that of the conventional treatment group (all P<0.01),
      and the systolic pressure and diastolic pressure of telmisartan group were
      significantly lower than that of the benazepril group(both P<0.01) .The
      expression of ACE2 mRNA in monocyte-derived macrophages were significantly lower
      in essential hypertensive patients than that in control group (P<0.01). After
      having been treated for 4 weeks and 12 weeks, the expression of ACE2 mRNA in
      monocyte-derived macrophages of hypertensive patients in telmisartan and
      benazepril groups were significantly higher than that in conventional treatment
      group (all P<0.01), and the expression of ACE2 mRNA in telmisartan group was
      significantly higher than that in benazepril group (both P<0.01). CONCLUSION:
      PPAR-gamma agonist could increase the ACE2 mRNA expression in monocyte-derived
      macrophages of essential hypertensive patients.

PMID- 22954123
TI  - Effect of Pseudomonas aeruginosa on the expressions of matrix metalloproteinase-9
      and tissue inhibitor of metalloproteinase-1 in the airway of bronchiectasis
      patients.
AB  - OBJECTIVE: To study the expressions of matrix metalloproteinase-9 (MMP-9) and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) in the airway of bronchiectasis
      (BE) patients, and evaluate the effect of pseudomonas aeruginosa (PAE) on the
      expression of TIMP-1 and MMP-9. METHODS: In this case-control study, subjects
      were divided into BE group and control group, and the BE group was further
      divided into PAE group and other bacteria group based on the culture results of
      bronchoalveolar lavage fluid (BALF). BALF was obtained by bronchoscopy, the
      expressions of MMP-9 and TIMP-1 were determined by ELISA, then the ratio of TIMP
      1/MMP-9 was calculated. Furthermore, the tissue of bronchic endomembrane was
      obtained by transbronchial biopsy and the expressions of MMP-9 and TIMP-1 were
      determined using immunohistochemical method. RESULTS: The levels of MMP-9 in the
      BALF of PAE group and other bacteria group were significantly higher than that in
      control group (P=0.0000 both), and the expressions of MMP-9 in bronchic
      endomembrane of PAE group and other bacteria group were also significantly higher
      (P=0.0421 and 0.0003, respectively). The level of TIMP-1 in BALF of PAE group was
      significantly lower than that in other bacteria group (P=0.0324). The ratio of
      TIMP-1/MMP-9 in BALF of BE group was significantly lower than that in control
      group(P=0.0000), and this ratio of PAE group was significantly lower than those
      in both other bacteria group and control group (P=0.0026 and 0.0000,
      respectively). CONCLUSION: PAE infection in BE patients can suppress the
      expression of TIMP-1 and stimulate the expression of MMP-9, and thus make the
      disease even worse.

PMID- 22954124
TI  - Association of genetic polymorphisms of aldehyde dehydrogenase-2 and cytochrome
      P450 2E1-RsaI and alcohol consumption with oral squamous cell carcinoma.
AB  - OBJECTIVE: To investigate the association of the polymorphisms of aldehyde
      dehydrogenase-2(ALDH2) and CYP2E1-RsaI genes and alcohol consumption with oral
      squamous cell carcinoma (OSCC). METHODS: The genetic polymorphisms of ALDH2 and
      CYP2E1-RsaI were determined by polymorphism-polymerase chain reaction (PCR)
      technique in the peripheral blood leukocytes of 320 OSCC patients and 320 non
      cancer controls. RESULTS: The frequencies of ALDH2 variant genotypes and CYP2E1
      RsaI (c2/c2) were 70.94% and 39.06% in the OSCC group and 43.44% and 20.62% in
      the control group (both P<0.01). The risk of OSCC with ALDH2 variant genotypes
      was significantly higher than that in control group (OR=3.178, 95% CI=1.917
      4.749), whereas the subjects carried with CYP2E1-RsaI (c2/c2) also had a high
      risk of OSCC (OR=2.467, 95%CI=1.783-4.045). Combined analysis of the
      polymorphisms showed that percentage of ALDH2 variant genotypes/CYP2E1-RsaI
      (c2/c2) in OSCC group and control group was 32.19% and 6.25%, respectively
      (P<0.01). Carriers of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) had a high risk
      of OSCC (OR=9.792, 95%CI=3.583-12.472). The percentage of alcohol consumption was
      significantly higher in OSCC group than in the control group (OR=2.861, 95%
      CI=1.541-4.781, P<0.01), and ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2)
      showed synergic effects with alcohol consumption for the increased risk of OSCC
      (OR=41.152, 95%CI=19.903-67.551). CONCLUSION: The polymorphisms of ALDH2 and
      CYP2E1-RsaI genes and alcohol consumption, independently and synergically,
      increase the risk of OSCC.

PMID- 22954125
TI  - Application value of apparent diffusion coefficient in differentiation of brain
      radiation-injuries and glioma recurrence.
AB  - OBJECTIVE: To evaluate application value of apparent diffusion coefficient (ADC)
      in differentiating brain radiation-injuries and glioma recurrence. METHODS:
      Totally 23 patients [18 men and 5 women aged 32 to 67 years (mean: 47 years)]
      with previously resected and irradiated glioma were examined by using a 3.0T MR
      Scanner, including conventional and diffusion weighted image (DWI) sequences. All
      the cases were proved by pathology or clinical follow-up. Postprocessing of ADC
      maps was performed by using Functool software (AW 4.3, GE Healthcare), and the
      regions of interest (ROIs) were manually drawn on ADC maps in the area
      corresponding to the contrast-enhancing area on post-contrast axial T1-weighted
      images, avoiding the hemorrhage or necrosis. The ADC values were calculated
      automatically. ADC values were measured 10 times in order to reduce errors, and
      mean ADC value, maximum ADC value, and minimum ADC value were acquired. RESULTS:
      Both recurrent glioma and irradiated necrosis tended to have hemorrhage,
      necrosis, and edema. The mean ADC value and maximum ADC value were lower in the
      recurrent tumor group than in the radiation-injuries group, but no statistical
      difference was achieved. However, the minimum ADC value was significantly lower
      in the recurrent tumor group than in the radiation-injuries group (P=0.016).
      CONCLUSION: The minimum ADC value can be used as an useful tool in
      differentiating tumor recurrence from radiation-injuries.

PMID- 22954126
TI  - Clinical characteristics of hereditary and sporadic medullary thyroid carcinoma.
AB  - OBJECTIVE: To study the clinical characteristics and outcomes of the hereditary
      medullary thyroid carcinoma (HMTC) and the sporadic medullary thyroid carcinoma
      (SMTC). METHODS: The clinical data of 78 patients with medullary thyroid
      carcinoma who underwent surgery in our hospital between July 1980 and May 2011
      were retrospectively analyzed. RESULTS: Of these 78 patients, there were 23 HMTC
      cases and 55 SMTC cases. The HMTC group was significantly younger age of onset
      [(36.4+/-13.5) years vs. (46.6+/-11.2) years, P<0.01] and a lower pre/post
      operative serum calcitonin levels [(850.4+/-110.20) ng/L vs. (1450.4+/-118.3)
      ng/L, P<0.01 and (410.8+/-133.2) ng/L vs. (1585.4+/-129.5) ng/L, P<0.01] than the
      SMTC group. In addition, the mean tumor diameter was also significantly smaller
      in the HMTC group (14.3 mm vs. 21.0 mm in SMTC group, P<0.05). Tumor
      multifocality was seen in a significantly higher proportion of HMTC cases
      compared with the SMTC cases (56.6% vs. 29.1%, P<0.05). The overall 10-year
      survival was 100% in HMTC group and 80.2% in SMTC group (P<0.05). CONCLUSION:
      HMTC has a better prognosis than SMTC.

PMID- 22954127
TI  - Clinical analysis of 19 cases of adult primary mediastinal liposarcoma.
AB  - OBJECTIVE: To explore the pathoclinical features of adult primary mediastinal
      liposarcoma and their correlation with the prognosis. METHODS: The clinical data
      of 19 patients with adult primary mediastinal liposarcoma who were treated in our
      hospital between 1970 and 2011 were retrospectively analyzed. Eighteen patients
      underwent open thoracic tumor excisions for at least one time, and the remaining
      one patient only received biopsy surgery. Histopathological results after surgery
      revealed that 6 well-differentiated type tumors, 6 myxoid type tumors, 3
      pleomorphic type tumors, 2 mixed type tumors, and 2 un-classified tumors.
      RESULTS: Among 6 patients with well-differentiated type tumors, 1 died after
      having been survived for 10 years; 5 were still alive, with a mean duration of
      126.2 months,the 5-year survival rate was 100%. Among 6 patients with myxoid type
      tumors, 5 patients had follow-up data, with a mean survival of 26.2 months. Among
      3 patients with pleomorphic type tumors, only one patient had follow-up data: the
      patient finally died, with a survival of 34 months. Of 2 patients with mixed type
      tumors, only one patient had follow-up data: the patient survived 8 months and
      died. Of 2 patients with un-classified type tumors, one had follow-up data: the
      patient lived for 24 months and died. CONCLUSIONS: Mediastinal liposarcoma is a
      rare disease. Surgery is the primary therapeutic modality. Different pathological
      subtypes have different epidemiological features, biological behaviors, and
      malignant potentials. Pathological subtype is an important prognosis factor.
      Patients with well-differentiated tumors have much better prognosis than those
      with other subtypes.

PMID- 22954128
TI  - Site-specific pathology in breast reduction mammoplasty.
AB  - OBJECTIVE: To investigate the feasibility and clinical value of site-specific
      pathology in breast reduction mammoplasty. METHODS: Totally 127 patients who
      underwent breast reduction mammoplasty from June 2007 to June 2010 were included.
      Pathologic specimens were sent for frozen pathology according to the clock-wise
      method. Patients with confirmed cancer were arranged for conservative breast
      surgery. RESULTS: Of the 127 patients, 53 patients (41.7%) had gland hyperplasia;
      7 had fibroadenoma (5.5%); 1 (0.79%) had ductal carcinoma in situ, who underwent
      breast conserving surgery, following by chemotherapy and radiotherapy, no relapse
      was noted during the three-year follow-up. CONCLUSION: Clock-wise method is
      useful to locate the tumor and ensure the patients to receive skin-spared breast
      resection even cancer is detected.

PMID- 22954129
TI  - Research advance in application of metabonomics in cardiovascular diseases.
AB  - Metabonomics is a systematic science that mainly studies the dynamic changes of
      endogenous metabolites after a biological system is stimulated or disturbed. Its
      application in cardiovascular diseases has increasingly been explored, with an
      attempt to find valuable biomarkers and explore the underlying pathogenesis of
      cardiovascular diseases by profiling the metabolism in these patients. This
      article summarized recent advances in this topic and outlines prospects for
      future developments.

PMID- 22954130
TI  - MicroRNA and cerebral ischemia.
AB  - MicroRNAs (miRNAs) are a class of highly conserved single-stranded RNA molecules
      that modulate gene translation. By targeting the mRNA of protein- coding genes,
      miRNAs play a critical role in neuronal differentiation, cell proliferation,
      apoptosis and metabolism. There are a lot of miRNAs in central nervous system,
      which are not only closely linked to development, differentiation and function of
      nerve cells, also play an important role in nerve lesions and dysfunction after
      cerebral ischemia. Specific miRNA through their own changes affect their target
      gene expression levels after focal cerebral ischemia, involving in the protection
      against apoptosis in neurons and regeneration after cerebral ischemia. A full
      understanding of the specific microRNA function and its underlying mechanism in
      the brain can provide a new strategy for the prevention, diagnosis, and treatment
      of ischemic cerebral injury at gene level.

PMID- 22954131
TI  - Research advance in effects of weightlessness or simulated weightlessness on
      tumor cells.
AB  - Weightless environment is a rare phenomenon on the ground where the interactions
      among cells and internal cellular structures disappear or become weakened.
      Studies on the biological features and molecular expression of tumors cells in
      weightlessness condition may provide new clues to the tumor initiation, process,
      diagnosis, and therapy.

PMID- 22954132
TI  - Advances in research on G protein-coupled inward rectifier K(+) channel gene.
AB  - G protein-coupled inward rectifier K(+) channel 4(GIRK4) is a G protein-coupled
      inward rectifier potassium channel family member. Encoded by the KCNJ5, it is
      widely distributed in the mammalian heart, brain, and other tissues and organs.
      Recent studies have demonstrated that the abnormal expression of GIRK4 gene is
      associated with atrial fibrillation, and meanwhile may be closely related to
      obesity, metabolic syndrome, and many other clinical conditions. Further research
      on the role the GIRK4 gene in the pathophysiology of these clinical conditions
      will definitely facilitate their clinical diagnosis and treatment.

PMID- 22954133
TI  - Obesity and cardiovascular diseases.
AB  - Obesity is becoming increasingly prevalent and thus has been a global public
      concern. Studies have demonstrated that obesity and its complications can cause
      an early onset of cardiovascular diseases (CVD), reduce the therapeutic efficacy
      of medical and invasive treatment, and thus increase the mortality. Meanwhile, it
      can also cause damage to the structure, electrophysiology, and myocardial
      function of heart. It can be a particularly important issue for women. On the
      other hand, heart injury can also affect the weight loss options and their
      outcomes. This article elucidates the relationship between obesity and its
      complications and CVD, and meanwhile proposes some new perspectives about the
      prevention of CVD.

PMID- 22954134
TI  - Finding driver pathways in cancer: models and algorithms.
AB  - BACKGROUND: Cancer sequencing projects are now measuring somatic mutations in
      large numbers of cancer genomes. A key challenge in interpreting these data is to
      distinguish driver mutations, mutations important for cancer development, from
      passenger mutations that have accumulated in somatic cells but without functional
      consequences. A common approach to identify genes harboring driver mutations is a
      single gene test that identifies individual genes that are recurrently mutated in
      a significant number of cancer genomes. However, the power of this test is
      reduced by: (1) the necessity of estimating the background mutation rate (BMR)
      for each gene; (2) the mutational heterogeneity in most cancers meaning that
      groups of genes (e.g. pathways), rather than single genes, are the primary target
      of mutations. RESULTS: We investigate the problem of discovering driver pathways,
      groups of genes containing driver mutations, directly from cancer mutation data
      and without prior knowledge of pathways or other interactions between genes. We
      introduce two generative models of somatic mutations in cancer and study the
      algorithmic complexity of discovering driver pathways in both models. We show
      that a single gene test for driver genes is highly sensitive to the estimate of
      the BMR. In contrast, we show that an algorithmic approach that maximizes a
      straightforward measure of the mutational properties of a driver pathway
      successfully discovers these groups of genes without an estimate of the BMR.
      Moreover, this approach is also successful in the case when the observed
      frequencies of passenger and driver mutations are indistinguishable, a situation
      where single gene tests fail. CONCLUSIONS: Accurate estimation of the BMR is a
      challenging task. Thus, methods that do not require an estimate of the BMR, such
      as the ones we provide here, can give increased power for the discovery of driver
      genes.

PMID- 22954135
TI  - State of the art in feedstuff analysis: a technique-oriented perspective.
AB  - The need for global feed supply traceability, the high-throughput testing demands
      of feed industry, and regulatory enforcement drive the need for feed analysis and
      make extremely complex the issue of the control and evaluation of feed quality,
      safety, and functional properties, all of which contribute to the very high
      number of analyses that must be performed. Feed analysis, with respect to animal
      nutritional requirements, health, reproduction, and production, should be
      multianalytically approached. In addition to standard methods of chemical
      analysis, new methods for evaluation of feed composition and functional
      properties, authenticity, and safety have been developed. Requirements for new
      analytical methods emphasize performance, sensitivity, reliability, speed,
      simplified use, low cost for high volume, and routine assays. This review
      provides an overview of the most used and promising methods for feed analysis.
      The review is intentionally focused on the following techniques: classical
      chemical analysis; in situ and in vitro methods; analytical techniques coupled
      with chemometric tools (NIR and sensors); and cell-based bioassays. This review
      describes both the potential and limitations of each technique and discusses the
      challenges that need to be overcome to obtain validated and standardized methods
      of analysis for a complete and global feed evaluation and characterization.

PMID- 22954136
TI  - Differences in primary health care delivery to Australia's Indigenous population:
      a template for use in economic evaluations.
AB  - BACKGROUND: Health economics is increasingly used to inform resource allocation
      decision-making, however, there is comparatively little evidence relevant to
      minority groups. In part, this is due to lack of cost and effectiveness data
      specific to these groups upon which economic evaluations can be based.
      Consequently, resource allocation decisions often rely on mainstream evidence
      which may not be representative, resulting in inequitable funding decisions. This
      paper describes a method to overcome this deficiency for Australia's Indigenous
      population. A template has been developed which can adapt mainstream health
      intervention data to the Indigenous setting. METHODS: The 'Indigenous Health
      Service Delivery Template' has been constructed using mixed methods, which
      include literature review, stakeholder discussions and key informant interviews.
      The template quantifies the differences in intervention delivery between best
      practice primary health care for the Indigenous population via Aboriginal
      Community Controlled Health Services (ACCHSs), and mainstream general
      practitioner (GP) practices. Differences in costs and outcomes have been
      identified, measured and valued. This template can then be used to adapt
      mainstream health intervention data to allow its economic evaluation as if
      delivered from an ACCHS. RESULTS: The template indicates that more resources are
      required in the delivery of health interventions via ACCHSs, due to their
      comprehensive nature. As a result, the costs of such interventions are greater,
      however this is accompanied by greater benefits due to improved health service
      access. In the example case of the polypill intervention, 58% more costs were
      involved in delivery via ACCHSs, with 50% more benefits. Cost-effectiveness
      ratios were also altered accordingly. CONCLUSIONS: The Indigenous Health Service
      Delivery Template reveals significant differences in the way health interventions
      are delivered from ACCHSs compared to mainstream GP practices. It is important
      that these differences are included in the conduct of economic evaluations to
      ensure results are relevant to Indigenous Australians. Similar techniques would
      be generalisable to other disadvantaged minority populations. This will allow
      resource allocation decision-makers access to economic evidence that more
      accurately represents the needs and context of disadvantaged groups, which is
      particularly important if addressing health inequities is a stated goal.

PMID- 22954138
TI  - The heat is on.

PMID- 22954137
TI  - Measurement and modeling of signaling at the single-cell level.
AB  - It has long been recognized that a deeper understanding of cell function, with
      respect to execution of phenotypic behaviors and their regulation by the
      extracellular environment, is likely to be achieved by analyzing the underlying
      molecular processes for individual cells selected from across a population,
      rather than averages of many cells comprising that population. In recent years,
      experimental and computational methods for undertaking these analyses have
      advanced rapidly. In this review, we provide a perspective on both measurement
      and modeling facets of biochemistry at a single-cell level. Our central focus is
      on receptor-mediated signaling networks that regulate cell phenotypic functions.

PMID- 22954139
TI  - Determination of phosphite in a eutrophic freshwater lake by suppressed
      conductivity ion chromatography.
AB  - The establishment of a sensitive and specific method for the detection of reduced
      phosphorus (P) is crucial for understanding P cycle. This paper presents the
      quantitative evidence of phosphite (P, +3) from the freshwater matrix
      correspondent to the typically eutrophic Lake Taihu in China. By ion
      chromatography coupled with gradient elution procedure, efficient separation of
      micromolar levels of phosphite is possible in the presence of millimolar levels
      of interfering ions, such as chloride, sulfate, and hydrogen carbonate in
      freshwater lakes. Optimal suppressed ion chromatography conditions include the
      use of 500 MUL injection volumes and an AS11 HC analytical column heated to 30 
      degrees C. The method detection limit of 0.002 MUM for phosphite was successfully
      applied for phosphite determination in natural water samples with recoveries
      ranging from 90.7 +/- 3.2% to 108 +/- 1.5%. Phosphite in the freshwater matrix
      was also verified using a two-dimensional capillary ion chromatography and ion
      chromatography coupled with mass spectrometry. Results confirmed the presence of
      phosphite in Lake Taihu ranging from 0.01 +/- 0.01 to 0.17 +/- 0.01 MUM, which
      correlated to 1-10% of the phosphate. Phosphite is an important component of P
      and may influence biogeochemical P cycle in lakes.

PMID- 22954140
TI  - TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver
      cancer cells.
AB  - BACKGROUND: Hypoxia is a common characteristic of solid tumors associated with
      reduced response to radio- and chemotherapy, therefore increasing the probability
      of tumor recurrence. The aim of this study was to identify new mechanisms
      responsible for hypoxia-induced resistance in breast cancer cells. METHODS: MDA
      MB-231 and HepG2 cells were incubated in the presence of taxol or etoposide
      respectively under normoxia and hypoxia and apoptosis was analysed. A whole
      transcriptome analysis was performed in order to identify genes whose expression
      profile was correlated with apoptosis. The effect of gene invalidation using
      siRNA was studied on drug-induced apoptosis. RESULTS: MDA-MB-231 cells incubated
      in the presence of taxol were protected from apoptosis and cell death by hypoxia.
      We demonstrated that TMEM45A expression was associated with taxol resistance.
      TMEM45A expression was increased both in MDA-MB-231 human breast cancer cells and
      in HepG2 human hepatoma cells in conditions where protection of cells against
      apoptosis induced by chemotherapeutic agents was observed, i.e. under hypoxia in
      the presence of taxol or etoposide. Moreover, this resistance was suppressed by
      siRNA-mediated silencing of TMEM45A. Kaplan Meier curve showed an association
      between high TMEM45A expression and poor prognostic in breast cancer patients.
      Finally, TMEM45 is highly expressed in normal differentiated keratinocytes both
      in vitro and in vivo, suggesting that this protein is involved in epithelial
      functions. CONCLUSION: Altogether, our results unravel a new mechanism for taxol
      and etoposide resistance mediated by TMEM45A. High levels of TMEM45A expression
      in tumors may be indicative of potential resistance to cancer therapy, making
      TMEM45A an interesting biomarker for resistance.

PMID- 22954141
TI  - Enantioselective total synthesis of pladienolide B: a potent spliceosome
      inhibitor.
AB  - An enantioselective and convergent total synthesis of pladienolide B (1) is
      described. Pladienolide B binds to the SF3b complex of a spliceosome and inhibits
      mRNA splicing activity. The synthesis features an epoxide opening reaction, an
      asymmetric reduction of a beta-keto ester, and a cross metathesis strategy for
      the side chain synthesis.

PMID- 22954142
TI  - 11C-Methionine positron emission tomographic imaging of biologic activity of a
      recurrent glioblastoma treated with stereotaxy-guided laser-induced interstitial
      thermotherapy.
AB  - In patients with recurrent glioblastoma multiforme (GBM), local minimally
      invasive treatment modalities have gained increasing interest recently because
      they are associated with fewer side effects than open surgery. For example, local
      tumor coagulation by laser-induced interstitial thermotherapy (LITT) is such a
      minimally invasive technique. We monitored the metabolic effects of stereotaxy
      guided LITT in a patient with a recurrent GBM using amino acid positron emission
      tomography (PET). Serial 11C-methyl-L-methionine positron emission tomography
      (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a
      hybrid PET/CT system in a patient with recurrent GBM before and after LITT. To
      monitor the biologic activity of the effects of stereotaxy-guided LITT, a
      threshold-based volume of interest analysis of the metabolically active tumor
      volume (MET uptake index of >= 1.3) was performed. A continuous decline in
      metabolically active tumor volume after LITT could be observed. MET-PET seems to
      be useful for monitoring the short-term therapeutic effects of LITT, especially
      when patients have been pretreated with a multistep therapeutic regimen. MET-PET
      seems to be an appropriate tool to monitor and guide experimental LITT regimens
      and should be studied in a larger patient group to confirm its clinical value.

PMID- 22954143
TI  - Contrast enhancement of the brain by folate-conjugated gadolinium
      diethylenetriaminepentaacetic acid-human serum albumin nanoparticles by magnetic
      resonance imaging.
AB  - Different from regular small molecule contrast agents, nanoparticle-based
      contrast agents have a longer circulation time and can be modified with ligands
      to confer tissue-specific contrasting properties. We evaluated the tissue
      distribution of polymeric nanoparticles (NPs) prepared from human serum albumin
      (HSA), loaded with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (Gd
      HSA-NP), and coated with folic acid (FA) (Gd-HSA-NP-FA) in mice by magnetic
      resonance imaging (MRI). FA increases the affinity of the Gd-HSA-NP to FA
      receptor-expressing cells. Clinical 3 T MRI was used to evaluate the signal
      intensities in the different organs of mice injected with Gd-DTPA, Gd-HSA-NP, or
      Gd-HSA-NP-FA. Signal intensities were measured and standardized by calculating
      the signal to noise ratios. In general, the NP-based contrast agents provided
      stronger contrasting than Gd-DTPA. Gd-HSA-NP-FA provided a significant contrast
      enhancement (CE) in the brain (p  =  .0032), whereas Gd-DTPA or Gd-HSA-NP did
      not. All studied MRI contrast agents showed significant CE in the blood, kidney,
      and liver (p < .05). Gd-HSA-NP-FA elicited significantly higher CE in the blood
      than Gd-HSA-NP (p  =  .0069); Gd-HSA-NP and Gd-HSA-NP-FA did not show CE in
      skeletal muscle and gallbladder; Gd-HSA-NP, but not Gd-HSA-NP-FA, showed CE in
      the cardiac muscle. Gd-HSA-NP-FA has potential as an MRI contrast agent in the
      brain.

PMID- 22954144
TI  - Norepinephrine transporter imaging in the brain of a rat model of depression
      using radioiodinated (2S, alphaS)-2-(alpha-(2-iodophenoxy)benzyl)morpholine.
AB  - To visualize the norepinephrine transporters (NETs) in various brain diseases, we
      developed radioiodinated (2S,alphaS)-2-(alpha-(2-iodophenoxy)benzyl)morpholine
      ((S,S)-IPBM). This radioligand achieved the basic requirements for NET imaging.
      In this study, we assessed the potential of radioiodinated (S,S)-IPBM as an
      imaging biomarker of NET to obtain diagnostic information about depression in
      relation to NET expression in the brain using a rat depression model. The ex vivo
      autoradiographic experiments using the (S,S)-[125I]IPBM showed significantly
      lower accumulation of radioactivity in the locus coeruleus (LC) and the
      anteroventricular thalamic nucleus (AVTN) of the depression group than in those
      of the control group. Consequently, in vitro autoradiographic experiments showed
      that NET maximum binding (Bmax) values in the LC and AVTN, known as NET-rich
      regions, were significantly decreased in the rat model of depression when
      compared to those of the control rats. In addition, there was an extremely good
      correlation between NET Bmax and (S,S)-IPBM accumulation (r  =  .98), an
      indication of radioiodinated IPBM as a quantitative NET imaging biomarker. The
      reduction in (S,S)-[125I]IPBM accumulation in the rat model of depression
      correlated with that of NET density. These results suggest that (S,S)-[123I]IPBM
      has potential as an imaging biomarker of NET to obtain diagnostic information
      about major depression.

PMID- 22954145
TI  - Integrin alphavbeta3-targeted dynamic contrast-enhanced magnetic resonance
      imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD
      conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic
      treatment response in a mouse xenograft tumor model.
AB  - The purpose of this study was to validate an integrin alphavbeta3-targeted
      magnetic resonance contrast agent, PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2, for its
      ability to detect tumor angiogenesis and assess early response to antiangiogenic
      therapy using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI).
      Integrin alphavbeta3-positive U87 cells and control groups were incubated with
      fluorescein-labeled cRGD-conjugated dendrimer, and the cellular attachment of the
      dendrimer was observed. DCE MRI was performed on mice bearing KB xenograft tumors
      using either PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 or PEG-G3-(Gd-DTPA)6-(cRAD-DTPA)2.
      DCE MRI was also performed 2 hours after anti-integrin alphavbeta3 monoclonal
      antibody treatment and after bevacizumab treatment on days 3 and 6t. Using DCE
      MRI, the 30-minute contrast washout percentage was significantly lower in the
      cRGD-conjugate injection groups. The enhancement patterns were different between
      the two contrast injection groups. In the antiangiogenic therapy groups, a rapid
      increase in 30-minute contrast washout percentage was observed in both the LM609
      and bevacizumab treatment groups, and this occurred before there was an
      observable decrease in tumor size. The integrin alphavbeta3 targeting ability of
      PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 in vitro and in vivo was demonstrated. The 30
      minute contrast washout percentage is a useful parameter for examining tumor
      angiogenesis and for the early assessment of antiangiogenic treatment response.

PMID- 22954148
TI  - Imaging depths of near-infrared quantum dots in first and second optical windows.
AB  - Potential advantages of quantum dot (QD) imaging in the second optical window
      (SOW) at 1,000 to 1,400 nm over the first optical window (FOW) at 700 to 900 nm
      have attracted much interest. QDs that emit at 800 nm (800QDs) and QDs that emit
      at 1,300 nm (1,300QDs) are used to investigate the imaging depths at the FOW and
      SOW. QD images in biologic tissues are processed binarized via global
      thresholding method, and the imaging depths are determined using the criteria of
      contrast to noise ratio and relative apparent size. Owing to the reduced
      scattering in the SOW, imaging depth in skin can be extended by approximately
      three times for 1,300QD/SOW over 800QD/FOW. In liver, excitation of 1,300QD/SOW
      can be shifted to longer wavelengths; thus, the imaging depth can be extended by
      1.4 times. Effects of quantum yield (QY), concentration, incidence angle,
      polarization, and fluence rate F on imaging depth are comprehensively studied.
      Under F approved by the Food and Drug Administration, 1,300QDs with 50% QY can
      reach imaging depths of 29.7 mm in liver and 17.5 mm in skin. A time-gated
      excitation using 1,000 times higher F pulses can obtain the imaging depth of ~ 5
      cm. To validate our estimates, in vivo whole-body imaging experiments are
      performed using small-animal models.

PMID- 22954146
TI  - Simultaneous assessment of luminal integrity and vascular perfusion of the
      gastrointestinal tract using dual-channel near-infrared fluorescence.
AB  - Anastomotic complications such as stenosis and leakage in the gastrointestinal
      (GI) tract can cause high patient morbidity and mortality. To identify the
      potential preconditions of these complications intraoperatively, we explored the
      use of two 700 nm near-infrared (NIR) fluorophores administered intraluminally:
      (1) chlorella, an over-the-counter herbal supplement containing high
      concentrations of chlorophyll, and (2) methylene blue (MB). In parallel, we
      administered the 800 nm NIR fluorophore indocyanine green (ICG) intravenously to
      assess vascular function. Dual-channel, real-time intraoperative imaging and
      quantitation of the contrast to background ratio (CBR) were performed under
      normal conditions or after anastomosis or leakage of the stomach and intestines
      in 35 kg Yorkshire pigs using the Fluorescence-Assisted Resection and Exploration
      (FLARE) imaging system. Luminal integrity could be assessed with relatively high
      sensitivity with either chlorella or MB, although chlorella provided
      significantly higher CBR. ICG angiography provided assessment of blood perfusion
      of normal, ischemic, and anastomotic areas of the GI tract. Used simultaneously,
      700 nm (chlorella or MB) and 800 nm (ICG) NIR fluorescence permitted independent
      assessment of luminal integrity and vascular perfusion of the GI tract
      intraoperatively and in real time. This technology has the potential to identify
      critical complications, such as anastomotic leakage, intraoperatively, when
      correction is still possible.

PMID- 22954149
TI  - Fractal self-assembly of single-stranded DNA on hydrophobic self-assembled
      monolayers.
AB  - The self-assembled structures possess superior stability, biocompatibility and
      mechanical strength, and their study can provide insight into the use of creating
      novel biomaterials. Atomic force microscopy (AFM) images of single-stranded DNA
      (ssDNA) nanostructures show that well-ordered organization, high homogeneity, and
      molecular dimensions fractal-shaped fibers formed on a gold substrate covered
      with self-assembled monolayers (SAMs) of 1-hexadecanethiol (HDT). The nanoscaled
      architectures of ssDNA on HDT/Au changed remarkably following the process of
      diffusion-limited cluster aggregation (DLA) over time. The ssDNA fibers prefer to
      form on hydrophobic SAMs instead of hydrophilic SAMs, and the ssDNA has to have
      complementary regions in their sequences. This method might not be used only for
      the construction of fractal patterns, but also for the design and fabrication of
      functional DNA-based, self-assembled materials that exhibit self-similarity at
      multiple length scales.

PMID- 22954150
TI  - Adalimumab in the treatment of rheumatoid arthritis.
AB  - Adalimumab (ADA), a fully human monoclonal antibody against TNF-alpha is
      indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis,
      ankylosing spondylitis, juvenile idiopathic arthritis, Crohn's disease,
      ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with
      methotrexate or other disease-modifying antirheumatic drugs or as monotherapy.
      Studies comparing ADA with other TNF-alpha inhibitors are limited and are based
      mainly on meta-analyses of randomised controlled trials and large observational
      cohorts. In this study, the effectiveness and safety of ADA is compared with that
      of etanercept and infliximab.

PMID- 22954151
TI  - Hypothalamic dysfunction in obesity.
AB  - A growing number of studies have shown that a diet high in long chain SFA and/or
      obesity cause profound changes to the energy balance centres of the hypothalamus
      which results in the loss of central leptin and insulin sensitivity.
      Insensitivity to these important anorexigenic messengers of nutritional status
      perpetuates the development of both obesity and peripheral insulin insensitivity.
      A high-fat diet induces changes in the hypothalamus that include an increase in
      markers of oxidative stress, inflammation, endoplasmic reticulum (ER) stress,
      autophagy defect and changes in the rate of apoptosis and neuronal regeneration.
      In addition, a number of mechanisms have recently come to light that are
      important in the hypothalamic control of energy balance, which could play a role
      in perpetuating the effect of a high-fat diet on hypothalamic dysfunction. These
      include: reactive oxygen species as an important second messenger, lipid
      metabolism, autophagy and neuronal and synaptic plasticity. The importance of
      nutritional activation of the Toll-like receptor 4 and the inhibitor of NF-kappaB
      kinase subunit beta/NK-kappaB and c-Jun amino-terminal kinase 1 inflammatory
      pathways in linking a high-fat diet to obesity and insulin insensitivity via the
      hypothalamus is now widely recognised. All of the hypothalamic changes induced by
      a high-fat diet appear to be causally linked and inhibitors of inflammation, ER
      stress and autophagy defect can prevent or reverse the development of obesity
      pointing to potential drug targets in the prevention of obesity and metabolic
      dysfunction.

PMID- 22954152
TI  - Using isotopic fractionation to link precursor to product in the synthesis of (+/
      )-mephedrone: a new tool for combating "legal high" drugs.
AB  - Several recent deaths in the U.K. have been attributed to "legal high" drugs and
      in particular to (+/-)-4-methylmethcathinone ((+/-)-mephedrone). Recent
      literature has begun to focus on the chemical analysis of mephedrone and related
      substituted cathinones and methcathinones; however, no studies involving the
      application of stable isotope analysis to these compounds has yet emerged. Such
      studies have, for example, the potential to provide information linking the final
      products to a particular precursor by the manufacturer. In this study, the use of
      stable isotope profiling was explored to provide a possible connection between
      product and precursor chemicals. Six samples each of mephedrone were prepared
      using precursor chemicals from two different manufacturers, providing 12 samples
      in total. Synthesis was via a stable intermediate.

PMID- 22954153
TI  - Protective effects of Galla Rhois, the excrescence produced by the sumac aphid,
      Schlechtendalia chinensis, on transient focal cerebral ischemia in the rat.
AB  - Galla Rhois is formed by aphids, primarily Schlechtendalia chinensis Bell
      (Homoptera: Pemphigidae), on the leaf of sumac, Rhus javanica L. (Sapindales:
      Anacardiaceae). It is a tannin-rich herb that is widely used in traditional
      Korean medicine. Its various pharmacological effects, including its radical
      scavenging effects, have been reported. The purpose of the current study was to
      determine if these radical-scavenging effects can be confirmed using in vitro
      assays and to investigate its neuroprotective effects, optimal dosage,
      mechanisms, and therapeutic time window in an animal model of stroke. Galla Rhois
      85% methanol extract (GRE) exhibited potent and dose-dependent radical-scavenging
      effects on various radicals. Oral administration of GRE (300 mg/kg) in a
      transient focal cerebral ischemia rat model (two hours of occlusion followed by
      22 hours of reperfusion) reduced the brain infarct volume by 37.5%. It also
      improved sensory motor function and reduced lipid-peroxidation in middle cerebral
      artery occlusion. However, it did not have any inhibitory effects on brain edema.
      The time window study revealed that pre- and co-treatment with GRE had protective
      effects, but post-treatment with GRE (three or six hours after ischemia) did not
      have protective effects. In conclusion, GRE had potent radical-scavenging
      activities and neuroprotective effects in a rat model of stroke when it was pre-
      and co-administered. The optimal dosage may be around 300 mg/kg for oral
      administration.

PMID- 22954154
TI  - Biological characterization of folate-decorated biodegradable polymer
      platinum(II) complex micelles.
AB  - A biodegradable and amphiphilic copolymer, poly(ethylene glycol)-block-poly(l
      lactide-co-2-methyl-2-carboxyl-propylene carbonate) (mPEG-b-P(LA-co-MCC)), which
      contains pendant carboxyl groups, was chosen as a drug carrier for the active
      anticancer part (diaminocyclohexane platinum, DACH-Pt) of oxaliplatin to form
      mPEG-b-P(LA-co-MCC/Pt) complex. A folic acid-conjugated copolymer, folic acid
      poly(ethylene glycol)-block-poly(L-lactide) (FA-PEG-PLA), with similar chemical
      structure was chosen for targeting. Multifunctional micelles were successfully
      prepared by a coassembling method. In vitro evaluation was performed by using
      SKOV-3 and MCF-7 cancer cells. In vivo blood clearance of platinum was studied,
      and the results show that micelles exhibit longer blood circulation after iv
      injection. Pt biodistribution was studied by measuring its levels in plasma,
      organs, and tumors, especially in tumor cell DNA, by atomic absorption and
      inductively coupled plasma mass spectrometry. Antitumor activity was assessed in
      mice bearing H22 liver cancers, and the results showed that the micelles with FA
      moieties exhibited greater antitumor efficacy than those without FA or
      oxaliplatin. Therefore, these novel multifunctional platinum micelles have great
      potential in future clinical application.

PMID- 22954155
TI  - One-pot access to a library of structurally diverse nicotinamide derivatives via
      a three-component formal aza [3 + 3] cycloaddition.
AB  - The three-component formal [3 + 3] aza-annulation between chalcones, beta
      ketoamides, and ammonium acetate in the presence of CAN as a Lewis acid affords
      good to excellent yields of highly substituted nicotinamides or their fused
      derivatives. This transformation leads to the formation of one C-C and two C-N
      bonds in a single synthetic operation and involves up to five individual steps. 

PMID- 22954156
TI  - Comparison of genetic diversity structure analyses of SSR molecular marker data
      within apple (Malus*domestica) genetic resources.
AB  - The aim of this study was to compare traditional hierarchical clustering
      techniques and principal coordinate analysis (PCoA) with the model-based Bayesian
      cluster analyses in relation to subpopulation differentiation based on breeding
      history and geographical origin of apple (Malus*domestica Borkh.) cultivars and
      landraces. We presented the use of a set of 10 microsatellite (SSR) loci for
      genetic diversity structure analyses of 273 apple accessions from national
      genetic resources. These SSR loci yielded a total of 113 polymorphic SSR alleles,
      with 5-18 alleles per locus. SSR molecular data were successfully used in binary
      and allelic input format for all genetic diversity analyses, but allelic
      molecular data did not reveal reliable results with the NTSYS-pc and BAPS
      softwares. A traditional cluster analysis still provided an easy and effective
      way for determining genetic diversity structure in the apple germplasm
      collection. A model-based Bayesian analysis also provided the clustering results
      in accordance to traditional cluster analysis, but the analyses were distorted by
      the presence of a dominant group of apple genetic resources owing to the narrow
      origin of the apple genome. PCoA confirmed that there were no noticeable
      differences in genetic diversity structure of apple genetic resources during the
      breeding history. The results of our analyses are useful in the context of
      enhancing apple collection management, sampling of core collections, and
      improving breeding processes.

PMID- 22954157
TI  - Aggregation-induced fast crystal growth of SnO2 nanocrystals.
AB  - In this paper, we report an ultrafast growth of SnO(2) nanocrystals directly from
      ~4 to ~350 nm in a hydrothermal process (250  degrees C, time >180 h). The
      crystal growth system is characterized by "either small or large" particle size;
      that is, only two differently sized SnO(2) particles, either several nanometers
      or ~350 nm, coexist. During the fast growth process, SnO(2) nanoparticles
      assembled to form densely aggregated aggregates that can quickly transform to big
      (bulk-like) crystals. The kinetic analysis, for the first time, point outs that
      the fast growth reaction (from nanocrystal aggregates to bulk-like crystals)
      follows a first-order reaction law with a very large kinetic pre-exponent factor
      (1.53 * 10(27) h(-1)), which is in line with our proposed aggregation-induced
      fast crystal growth mechanism. Small-angle X-ray scattering (SAXS) study of the
      aggregates supports that the onset of the fast growth is closely related to an
      increase in the aggregation degree of the aggregates. Moreover, disintegrating
      the aggregation state via introduction of other particles (Al(2)O(3)) into the
      system prohibited the fast growth. The finding in this work provides new threads
      for syntheses of novel nanomaterials that may possess properties not readily
      obtained via conventional crystal growth routes.

PMID- 22954158
TI  - The complete mitochondrial genome of the beet armyworm Spodoptera exigua (Hubner)
      (Lepodiptera: Noctuidae).
AB  - The complete mitochondrial genome of the beet armyworm Spodoptera exigua (Hubner)
      (Lepodiptera: Noctuidae) was determined (GenBank accession number JX316220). The
      genome is 15,365 bp long with 37 typical animal mitochondrial genes and an A+T
      rich region. As in other sequenced mitochondrial genomes of Lepidoptera, trnM was
      rearranged to the upstream of trnI-trnQ-trnM cluster compared with the pupative
      ancestral arrangement of insects. All protein-coding genes start with ATN start
      codon except for the gene cox1, which uses CGA as in other lepidopteran species.
      Eight protein-coding genes stop with termination codon TAA. Five protein-coding
      genes use incomplete stop codons TA or T. The A+T-rich region is located between
      rrnS and trnM with a length of 331 bp. This is the third completely sequenced
      mitochondrial genome from the family Noctuidae of Lepidoptera.

PMID- 22954159
TI  - Depression, cardiometabolic function and left ventricular hypertrophy in African
      men and women: the SABPA study.
AB  - Depressive symptoms are associated with an increased risk for developing
      cardiovascular diseases, driven by its link to the metabolic syndrome (MetS).
      This phenomenon, however, still needs to be investigated in the African
      population. The aim of this study is to investigate the association between left
      ventricular hypertrophy (LVH) and MetS risk markers in a determined sample. The
      researchers stratified Black African men and women into with depressive symptoms
      (D) or without depressive symptoms (ND) group, based on the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition criteria score. Fasting
      MetS, chronic hyperglycemia (HbA1c), ambulatory blood pressure (BP) and Cornell
      product-LVH (CP-LVH) in ECG measures were obtained. Depressive symptoms were
      reported in 45.3% of the sample. Independent of depression status, African men
      and women revealed a pre-diabetic state (glycated hemoglobin >5.7%). CP-LVH was
      associated with decreased low high-density lipoprotein cholesterol in D African
      women. In D African men, systolic BP (P = .001) and HbA1c (P = .08) explained 64%
      and 31% of the variation in LVH, respectively. In conclusion, depressive symptoms
      in Black African women were associated with a measure of target end organ damage,
      CP-LVH, and this association was driven by a metabolic factor. In Black African
      men, independent of depressive symptoms, LVH, was driven by cardiometabolic
      factors, namely SBP and HbA1c.

PMID- 22954160
TI  - Spectral changes of Atlantic salmon ( Salmo salar L.) muscle during cold storage
      as affected by the oxidation state of heme.
AB  - The spectra of fresh salmon fillets change due to storage and packaging
      atmospheres. The aim of this study was to demonstrate the effects of heme
      oxidation states on spectral development in salmon fillets and to investigate the
      origin of a shoulder peak representing important spectral variations during
      storage. Hyperspectral images of fresh salmon fillets and mince with various
      water contents were collected during storage under different atmospheres. In
      addition, the absorption spectra of extracted salmon hemoglobin and its
      derivatives (methemoglobin and deoxyhemoglobin) were obtained. Air storage
      resulted in an increased similarity between spectra of methemoglobin and salmon
      fillets in principal component analysis. Results from the mince storage
      demonstrated that absorption features at the shoulder peak could be related to
      water content in the salmon muscle. This study established that the formation of
      oxidized heme is the primary source of spectral variations that occur during air
      storage of fresh salmon. Changes in the status of heme due to storage and
      packaging can influence the appearance of the underlying water absorption at the
      shoulder peak and create variations in the salmon spectra.

PMID- 22954161
TI  - Optimal white light control of the negative to neutral to positive charge
      transition (NeNePo) in the electronic manifold of the silver trimer.
AB  - Control over the electronic state of the Ag(3) cluster is approached via a
      progression of ultrafast photoinduced transitions within the full electronic
      manifold of the negative to the neutral and finally the cationic state of the
      system. High-bandwidth supercontinuum laser pulses ranging from 500 to 950 nm are
      employed for addressing the wide range of electronic resonance conditions
      associated with the ladder climbing process of a tandem photoelectron detachment
      and a resonance enhanced multiphoton ionization (REMPI). With the control of the
      phase over the full spectral envelope of the supercontinuum in a pulse shaper
      arrangement, pulse forms are generated with the aim of synchronizing ultrashort
      subpulse sequences to the characteristic dynamics of the system during charge
      reversal. Pulse forms ranging over several hundred femtoseconds in total duration
      and subpulse structures down to 15 fs duration with a variable spectral
      composition can be obtained for this purpose. A free optimization based on a
      closed-loop genetic algorithm is employed for ordering the subpulse sequences to
      match the structural evolution of the system. The effective control attainable in
      this scenario is evaluated in view of maintaining a defined sequence of
      electronic transitions within the complex dynamic response of the system during
      the photoexcitation. Further emphasis is made on analyzing the degree of control
      attainable in the nonlinear regime of multiphoton excitation at supercontinuum
      bandwidths.

PMID- 22954162
TI  - Induction of angiogenesis by controlled delivery of vascular endothelial growth
      factor using nanoparticles.
AB  - AIMS: The study reports the feasibility and efficiency of vascular endothelial
      growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl
      methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis.
      METHODS: The nanoparticles were prepared using phase separation method, and the
      drug release profile was determined by ELISA study. The bioactivity of VEGF
      incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay.
      A rabbit hind limb ischemia model was employed to evaluate the in vivo
      therapeutic effect. Blood perfusion was measured by single-photon emission
      computed tomography (SPECT). Vessel formation was evaluated by contrast
      angiography and immunohistochemistry. RESULTS: The nanoparticles synthesized were
      spherical in shape with evenly distributed size of about 130 +/- 3.5 nm. The VEGF
      encapsulated was released in a biphase manner, with the majority of 69% released
      over 1-12 days. Tube formation assays showed increased tubular structures by VEGF
      NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP
      significantly increased blood perfusion compared with empty nanoparticles (both P
      < 0.001), but it was much higher in VEGF-NP-treated limbs (P < 0.001). Contrast
      angiography and immunohistological analysis also revealed more significant
      collateral artery formation and higher capillary density in VEGF-NP-treated
      limbs. CONCLUSIONS: Dex-GMA and gelatin-based nanoparticles could provide
      sustained release of VEGF and may serve as a new way for angiogenesis.

PMID- 22954163
TI  - Evaluation of the impact of a diabetes education curriculum for school personnel
      on disease knowledge and confidence in caring for students.
AB  - BACKGROUND: School personnel may lack knowledge of diabetes and be unprepared to
      address the needs of students with type 1 diabetes. This project evaluated the
      effectiveness of a type 1 diabetes education program for school personnel on
      increasing knowledge of diabetes and confidence in caring for students with
      diabetes. METHODS: Two types of diabetes education programs were created for
      school personnel. The basic program provided a 60-minute overview of diabetes.
      The expanded program, intended for volunteer health aides, provided participants
      with a more in-depth overview of diabetes during a 180-minute session, including
      demonstrations of how to assist students with insulin injections. Instruments
      were created to assess changes in diabetes-related knowledge and confidence in
      caring for students. Separate knowledge instruments were created for the basic
      and expanded programs. Knowledge instruments were administered before and after
      delivery of the education programs to both groups. Confidence instruments were
      administered before and after for persons completing the expanded program.
      RESULTS: A total of 81 school personnel participated in the basic (N = 44) or
      expanded programs (N = 37). Overall knowledge regarding diabetes significantly
      increased in both the basic and expanded programs from baseline (p < .001).
      Confidence in caring for students with diabetes also increased from pretest to
      posttest, both for overall confidence and each individual item (p < .001).
      CONCLUSIONS: Educational programs offered for school personnel can lead to
      increased knowledge and increased confidence in caring for students with
      diabetes, which may assist school personnel in addressing the needs of students
      with diabetes.

PMID- 22954164
TI  - Use of SPARK to promote after-school physical activity.
AB  - BACKGROUND: The after-school period is potentially an important venue for
      increasing physical activity for youth. We sought to assess the effectiveness of
      the Sports, Play, and Recreation for Youth (SPARK) program to increase physical
      activity and improve cardiorespiratory fitness and weight status among elementary
      students after school. METHODS: This quasi-experimental controlled study compared
      change in moderate to vigorous physical activity (MVPA), body mass index (BMI) z
      score, and cardiorespiratory fitness (VO(2) ) over 5 months between students in
      after-school programs exposed to SPARK versus controls. Participants were fifth
      grade students at 3 intervention schools (N = 48) and 3 control schools (N = 52).
      RESULTS: There was no difference between groups in mean change in MVPA, BMI z
      score, or cardiorespiratory fitness. After-school time dedicated to physical
      activity did not increase with the implementation of SPARK. Intervention
      students' self-assessment of their activity levels relative to their peers
      significantly increased compared to control students (p = .011). CONCLUSIONS: In
      this 5-month study, the SPARK program did not increase MVPA in the after-school
      setting. Increasing the amount of time dedicated to physical activity may be as
      important as the curriculum used to effectively increase physical activity after
      school.

PMID- 22954165
TI  - Obesity prevention in young schoolchildren: results of a pilot study.
AB  - BACKGROUND: Overweight and obesity occur in 17% of children in the United States.
      Complications of excess weight in Americans cause 216,000 to 300,000 deaths
      yearly and cost $147 billion. METHODS: A convenience sample of 14 intervention
      and 15 control schools in the Catholic Diocese of Pittsburgh was used. A program
      to improve lifestyle (Values Initiative Teaching About Lifestyle [VITAL(r)]), was
      implemented in young children to encourage healthy eating and appropriate
      physical activity. Students had annual evaluations of height and weight over a 2
      year period, and teachers participating in VITAL completed questionnaires
      regarding the program. Changes in age- and sex-adjusted body mass index (BMI)
      percentiles in control and intervention groups were compared using linear mixed
      models regression. RESULTS: VITAL was highly rated by teachers and was popular
      with children. Over the 2-year period, adjusted mean BMI percentiles declined
      from 66.1 to 65.0 in control children and from 62.8 to 58.9 in intervention
      children. The rates of change in the 2 groups were significantly different (p =
      .015). CONCLUSION: VITAL improves lifestyle of young schoolchildren, is
      inexpensive, easy to implement, and should be expanded to improve health and
      reduce healthcare's financial burden.

PMID- 22954166
TI  - Alliance for a Healthier Generation's competitive beverage and food guidelines:
      do elementary school administrators know about them and do they report
      implementing them?
AB  - BACKGROUND: The availability of competitive foods in schools is a modifiable
      factor in efforts to prevent childhood obesity. The Alliance for a Healthier
      Generation launched the Healthy Schools Program in 2006 to encourage schools to
      create healthier food environments, including the adoption of nutritional
      guidelines for competitive beverages and foods. This study examines nationwide
      awareness and implementation of the guidelines in US public elementary schools.
      METHODS: Data were collected from a nationally representative sample of
      elementary schools using mail-back surveys in 2006-2007, 2007-2008, 2008-2009,
      and 2009-2010. RESULTS: From 2006-2007 to 2009-2010, awareness of the Alliance's
      beverage guidelines increased from 35.0% to 51.8% among school administrators (p
      < .01); awareness of the food guidelines increased from 29.4% to 40.2% (p < .01).
      By 2009-2010, almost one third of the schools that sold competitive beverages and
      foods reported having implemented or being in the process of implementing the
      guidelines. Implementation was higher among schools from Southern states. Schools
      with a majority of Black or Latino students were less likely to implement the
      guidelines. CONCLUSIONS: Awareness and implementation of the Alliance's beverage
      and food guidelines has significantly increased since the 2006-2007 school year,
      indicating successful diffusion of the guidelines. However, many administrators
      at schools who sold competitive products were not aware of the guidelines,
      indicating a need for continued efforts. In addition, lower implementation among
      schools serving minority students suggests that the Alliance's targeted efforts
      to provide intensive technical assistance to such schools is warranted and
      necessary.

PMID- 22954167
TI  - Obesity and health risk of children in the Mississippi Delta.
AB  - BACKGROUND: Mississippi (MS) Delta adults and youth report obesity rates far
      exceeding those of the state and nation. State law requires in-school physical
      activity and nutrition practices to address childhood obesity but does not
      require evaluation of outcomes, specifically the impact on weight-related
      outcomes. This paper offers 3 things: (1) describes the weight status of
      elementary school-age children in the MS Delta; (2) explains the importance of
      including waist-to-height ratio (WHtR) values when reporting body mass index
      (BMI); and (3) provides impetus for policy that requires weight-related health
      risk, as measured by WHtR, to be assessed regularly as a means to evaluate school
      health policy. METHODS: We took anthropometric measures in a cross-sectional
      investigation of 1136 children from 11 public elementary schools in the MS Delta.
      Measures included BMI, waist circumference (WC) and WHtR. RESULTS: The prevalence
      of overweight and obesity (BMI >=85th percentile) was 47.1% (18.3% overweight and
      28.8% obese). In this sample, 59.9% and 42.0% were "at risk" for weight-related
      chronic disease based on WC (>=75th percentile) and WHtR (>0.5), respectively.
      The differences in these proportions were statistically significant. The
      predominantly black districts reported higher on all of the weight-related
      measures. CONCLUSIONS: Investigators recommend the assessment of health policy
      include measures of health risk in addition to BMI, namely WHtR as it accounts
      for growth in both WC and height over age. Furthermore, WHtR is a more accurate
      indicator of fat distribution and health risk than WC alone.

PMID- 22954168
TI  - A menu for health: changes to New York City school food, 2001 to 2011.
AB  - BACKGROUND: The high prevalence of obesity puts children at risk for chronic
      diseases, increases health care costs, and threatens to reduce life expectancy.
      As part of the response to this epidemic, the New York City (NYC) Department of
      Education (DOE)--the nation's largest school district--has worked to improve the
      appeal and nutritional quality of school food. This article highlights some of
      the structural and policy changes that have improved the school food environment
      over the past decade, with the aim to share lessons learned and provide
      recommendations and resources for other districts interested in making similar
      modifications. METHODS: This article details changes DOE has implemented over 10
      years, including revised nutrition standards for school meals and competitive
      foods; new school food department staffing; food reformulations, substitutions,
      and additions; and transitions to healthier beverages. RESULTS: NYC's revised
      nutrition standards and hiring of expert staff increased availability of fruits
      and vegetables, whole grains, and low-fat dairy and decreased sugary beverages,
      and foods high in saturated fats and added sugars--the major contributors to
      discretionary calorie intake. DOE also introduced healthier beverages: switching
      from high-calorie, high-fat whole milk to low-fat milk and increasing access to
      water. CONCLUSIONS: NYC has successfully improved the quality of its school food
      environment and shown that healthier food service is possible, even under
      budgetary constraints. Several broad factors facilitated these efforts: fostering
      community partnerships and inter-agency collaboration, implementing policies and
      initiatives that target multiple sectors for greater impact, and working to make
      incremental improvements each year.

PMID- 22954169
TI  - Experiences of general practices with a participatory pay-for-performance
      program: a qualitative study in primary care.
AB  - The involvement of target users in the design choices of a pay-for-performance
      program may enhance its impact, but little is known about the views of
      participants in these programs. To explore general practices' experiences with
      pay-for-performance in primary care we conducted a qualitative study in general
      practices in the Netherlands. Thirty out of 65 general practices participating in
      a pay-for-performance program, stratified for bonus, were invited for a
      semistructured interview on feasibility, feedback and the bonus, spending of the
      bonus, unintended consequences, and future developments. Content analysis was
      used to process the resulting transcripts. We included 29 practices. The
      feasibility of the pay-for-performance program was questioned due to the
      substantial time investment. The feedback on clinical care, practice management
      and patient experience was mostly discussed in the team, and used for improvement
      plans, but was also qualified as annoying for one GP and for another GP it
      brought feelings of insecurity. Most practices considered the bonus a stimulus to
      improve quality of care, in addition to compensation for their effort and time
      invested. Distinctive performance features were not displayed, for instance, on a
      website. The bonus was mainly spent on new equipment or team building. Practices
      referred to gaming and focusing on those aspects that were incentivised ('tunnel
      vision') as unintended consequences. Future developments should be directed to
      absolute thresholds, new indicators to keep the process going, and an independent
      audit. Linking a part of the bonus to innovation was also suggested. The
      participants thought the pay-for-performance program was a labour-intensive
      positive breakthrough to stimulate quality improvement, but warned of unintended
      consequences of the program and the sustainability of the indicator set. 

PMID- 22954170
TI  - An improved model to predict physiologically based model parameters and their
      inter-individual variability from anthropometry.
AB  - We developed a population physiology model, physB, which provides a statistical
      description of the physiological characteristics in the human population, in
      terms of the physiological parameters that are needed in physiologically based
      pharmacokinetic modelling. The model predicts individual organ weights, blood
      flows and some respiratory parameters from anthropometric properties (body height
      and weight, age and gender). It draws on two existing models, PK-Pop and P(3)M,
      but various changes and improvements were made. The conceptual differences among
      the three models are discussed and they are quantitatively compared by running
      all three models for various specific combinations of anthropometric properties.

PMID- 22954171
TI  - Erythropoietin attenuates cardiac dysfunction by increasing myocardial
      angiogenesis and inhibiting interstitial fibrosis in diabetic rats.
AB  - BACKGROUND: Recent studies revealed that erythropoietin (EPO) has tissue
      protective effects in the heart by increasing vascular endothelial growth factor
      (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this
      study, we investigated the effect of EPO on ventricular remodeling and blood
      vessel growth in diabetic rats. METHODS: Male SD rats were randomly divided into
      3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic
      rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve
      weeks later, echocardiography was conducted, and blood samples were collected for
      counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial
      tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect
      the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was
      used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming
      growth factor beta (TGF-beta), and CD31 levels in the myocardium were determined
      by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of
      collagen type I, collagen type III, and Picrosirius Red staining were performed,
      and cardiomyocyte cross-sectional area was measured. RESULTS: After 12 weeks STZ
      injection, blood glucose increased significantly and remained consistently
      elevated. EPO treatment significantly improved cardiac contractility and reduced
      diastolic dysfunction. Rats receiving the EPO injection showed a significant
      increase in circulating EPCs (27.85 +/- 3.43%, P < 0.01) compared with diabetic
      untreated animals. EPO injection significantly increased capillary density as
      well as EPOR and VEGF expression in left ventricular myocardial tissue from
      diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and
      reduced TGF-beta expression. CONCLUSIONS: Treatment with EPO protects cardiac
      tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading
      to improved revascularization and the inhibition of cardiac fibrosis.

PMID- 22954172
TI  - Additional diagnostic value of tumor markers in cytological fluid for diagnosis
      of non-small-cell lung cancer.
AB  - BACKGROUND: Cytological fluid from a needle aspiration biopsy (NAB) is obtained
      directly from tumor tissue, therefore many biomarker candidates will be present
      in high concentrations. The aim of this study was to prospectively assess and
      validate the tumor markers CYFRA 21-1, CEA, and SCC in cytological fluid obtained
      from NAB samples to determine if they improved the performance of NAB for
      diagnosing non-small cell lung cancer (NSCLC). METHODS: A total of 194 patients
      (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions
      were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21-1,
      CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained
      during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL
      in serum and 15.7 ng/mL in cytological fluid for CYFRA 21-1, 5 ng/mL and 0.6
      ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. RESULTS: Of 194 patients, 139
      patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity
      increased significantly for NAB combined with cytological tumor markers compared
      with NAB alone (CYFRA 21-1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%,
      p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly
      for NAB combined with cytological CYFRA 21-1 compared with NAB alone (95.9%
      versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological
      CYFRA 21-1 was significantly larger than for NAB alone (0.966 versus 0.917, p =
      0.009). CONCLUSION: Of the tested tumor markers, cytological fluid measurements
      of CYFRA 21-1 improved the diagnostic performance of NAB for NSCLC.

PMID- 22954173
TI  - Socio-cultural factors surrounding mental distress during the perinatal period in
      Zambia: a qualitative investigation.
AB  - BACKGROUND: The presence of mental distress during pregnancy and after childbirth
      imposes detrimental developmental and health consequences for families in all
      nations. In Zambia, the Ministry of Health (MoH) has proposed a more
      comprehensive approach towards mental health care, recognizing the importance of
      the mental health of women during the perinatal period. AIM: The study explores
      factors contributing to mental distress during the perinatal period of motherhood
      in Zambia. METHODS: A qualitative study was conducted in Lusaka, Zambia with
      nineteen focus groups comprising 149 women and men from primary health facilities
      and schools respectively. FINDINGS: There are high levels of mental distress in
      four domains: worry about HIV status and testing; uncertainty about survival from
      childbirth; lack of social support; and vulnerability/oppression. CONCLUSION:
      Identifying mental distress and prompt referral for interventions is critical to
      improving the mental health of the mother and prevent the effects of mental
      distress on the baby. RECOMMENDATION: Strategies should be put in place to ensure
      pregnant women are screened for possible perinatal mental health problems during
      their visit to antenatal clinic and referral made to qualified mental health
      professionals. In addition further research is recommended in order to facilitate
      evidence based mental health policy formulation and implementation in Zambia.

PMID- 22954174
TI  - Copper-catalyzed electrophilic amination of alkenylzirconocenes with O
      benzoylhydroxylamines: an efficient method for synthesis of enamines.
AB  - Copper-catalyzed electrophilic amination of alkenylzirconocenes is accomplished
      under mild reaction conditions. The reaction tolerates a wide range of functional
      groups and can be used to prepare some hindered enamines.

PMID- 22954175
TI  - Confinement-induced states in the folding landscape of the Trp-cage miniprotein.
AB  - Although protein folding is typically studied in dilute solution, folding in a
      cell will be affected by interactions with other biomolecules and excluded volume
      effects. Here, we examine the effect of hydrophobic confinement on folding of the
      Trp-cage miniprotein. We used replica exchange molecular dynamics simulations to
      probe the differences between folding in the bulk, on a hydrophobic surface, and
      confined between two hydrophobic walls. In addition to promotion of helix
      formation due to reduced conformational entropy of the unfolded state upon
      confinement, adsorption of Trp-cage to a hydrophobic surface stabilizes
      intermediate structures not present in the bulk. These new intermediate
      structures may alter the folding mechanism and kinetics and show the importance
      of including environmental effects when studying protein folding.

PMID- 22954176
TI  - The complete mitochondrial genome of Megophrys shapingensis (Amphibia, Anura,
      Megophryidae).
AB  - The complete mitochondrial genome sequence of the Shaping horned toad Megophrys
      shapingensis, the first complete mitogenome from the family Megophryidae, was
      determined. The total length of this complete mitogenome was 17,631 bp,
      containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control
      region (D-loop). The gene arrangement and composition of the mitogenome were
      similar to those of most amphibians. The base composition on light strand was
      28.2% A, 31.5% T, 26.1% C, and 14.3% G. The D-loop region contained 10 copies of
      97-bp tandem repeats. The complete mitogenome sequence of M. shapingensis
      provided fundamental data for resolving phylogenetic and genetic problems related
      to this species.

PMID- 22954177
TI  - Nabiximols  in the treatment of spasticity, pain and urinary symptoms due to
      multiple sclerosis.
AB  - INTRODUCTION: Over the last two decades, experimental and clinical data suggest a
      therapeutic benefit of cannabis-based medicines for a variety of multiple
      sclerosis (MS) symptoms. Clinical trials, both with synthetic or plant-derived
      cannabinoids, have demonstrated clinical efficacy of cannabinoids for the
      treatment of spasticity, neuropathic pain and bladder dysfunction. Nabiximols, a
      1:1 mix of delta-9-tetrahydrocanabinol and cannabidiol extract from cloned
      chemovars, was licensed in the UK in 2010 and has also been approved in other
      European countries and Canada. The European Federation of Neurological Societies
      recommends that cannabis should be used only as a second or third line treatment
      in central neuropathic pain. AREAS COVERED: After a brief discussion of the
      endocannabinoid system, this review focuses on the use of cannabis to improve MS
      symptoms. More specifically, the authors have analyzed clinical studies on
      cannabis-based medicine extract (CBME), in particular nabiximols, in spasticity,
      as well as pain, and bladder dysfunction in MS. The authors have considered the
      large randomized controlled trials examining the psychological effects associated
      with cannabinoids use as well as long-term follow-up studies. EXPERT OPINION:
      Despite a number of trials with very promising results, there are still concerns
      related to relative paucity of data on long-term safety. Also, the long-term
      efficacy information in terms of the control of symptoms of a disease in which
      the natural history is progression is sparse. Therefore, further studies are
      required to improve the current knowledge of nabiximols.

PMID- 22954178
TI  - Effects of acute and chronic atorvastatin on cardioprotection of ischemic
      postconditioning in isolated rat hearts.
AB  - BACKGROUND: Myocardial reperfusion therapy remains the most effective strategy to
      limit infarct size and improve clinical outcome. However, reperfusion injury is
      still inevitable, and a number of strategies have been developed to ameliorate
      its lethal outcome. The beneficial roles of ischemic postconditioning (Ipost)
      have regained more interest in targeting myocardial reperfusion phase to improve
      cardioprotection. AIMS: This study was to determine whether acute or chronic
      treatment with atorvastatin affects cardioprotection when it was combined with
      Ipost. RESULTS: Acute or chronic atorvastatin treatment significantly reduced
      infarct size and recovered contractile dysfunction during reperfusion. When Ipost
      was combined with atorvastatin treatment, chronic, but not acute, atorvastatin
      therapy attenuated the cardioprotective effects of Ipost. Chronic, but not acute,
      atorvastatin treatment also abolished Ipost-induced phosphorylation level of Akt
      and endothelial nitric oxide synthase (eNOS). CONCLUSIONS: Chronic atorvastatin
      treatment could interfere with cardioprotective effects of Ipost on limiting
      infarct size and contractile dysfunction, possibly via inhibition of Akt and eNOS
      activity. This study suggests that Ipost should be used carefully when
      atorvastatin is taken by patients with AMI.

PMID- 22954179
TI  - Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast
      enhanced computed tomography to phenotype non-small cell lung carcinoma.
AB  - We applied modern molecular and functional imaging to the pretreatment assessment
      of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE
      CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to
      phenotype tumors. Seventy-four lung cancer patients were prospectively recruited
      for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures,
      there were 64 patients (35 males, 29 females; mean age [+/- SD] 67.5 +/- 7.9
      years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion
      value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake
      value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and
      SPV were used to define four vascular-metabolic phenotypes. There were
      associations (Spearman rank correlation [rs]) between tumor size and vascular
      metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE
      versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30)
      disease had mean (+/- SD) SUV/PE 0.36 +/- 0.28 versus 0.56 +/- 0.32 in later
      stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high
      vascularity phenotype was significantly more common among adenocarcinomas (p  = 
      .018), whereas the high metabolism with high vascularity phenotype was more
      common among squamous cell carcinomas (p  =  .024). Other non-small cell lung
      carcinoma tumor types demonstrated a high prevalence of the high metabolism with
      low vascularity phenotype (p  =  .028). We show that tumor subtypes have
      different vascular-metabolic associations, which can be helpful clinically in
      managing lung cancer patients to hone targeted therapy.

PMID- 22954180
TI  - Viral transgene expression delivered by repeat intraocular adenoviral vector
      injection: in vivo live imaging study.
AB  - We delivered adenovirus vector (Ad) via intravitreous injection and monitored
      transgene (luciferase) expression in living mice (BALB/c) at multiple time
      points. In vivo live imaging technology was able to assess dynamically
      intraocular luciferase expression in a single animal population throughout the
      entire experiment period. Using this information, we were able to determine the
      optimal time point for readministration of Ad into the eyes and to dynamically
      study the time course of expression of a second Ad administration. Optical
      imaging demonstrated the limited period of transgene expression in eyes.
      Significant transgene signal was also detected in livers. The repeat intraocular
      delivery of the adenovirus resulted in significant blunting of transgene
      expression in both eyes and livers compared to the initial delivery. Periocular
      corticosteroid (triamcinolone acetonide) injection combined with initial Ad
      delivery was effective to rescue luciferase expression on repeat Ad vector
      delivery. However, this effect was not observed when corticosteroid was combined
      with repeat Ad delivery. Although corticosteroid enhanced ocular transgene
      expression, it also increased transgene expression in liver, which has potential
      safety implications. This dynamic transgene expression in eyes was successfully
      traced and monitored via a live imaging technique.

PMID- 22954181
TI  - A novel near-infrared fluorescence imaging probe for in vivo neutrophil tracking.
AB  - The development and validation of a multiscopic near-infrared fluorescence (NIRF)
      probe, cinnamoyl-F-(D)L-F-(D)L-F-PEG-cyanine7 (cFlFlF-PEG-Cy7), that targets
      formyl peptide receptor on neutrophils using a mice ear inflammation model is
      described. Acute inflammation was induced in mice by topical application of
      phorbol-12-myristate-13-acetate to left ears 24 hours before probe
      administration. Noninvasive NIRF imaging was longitudinally performed up to 24
      hours following probe injection. The in vivo neutrophil-targeting specificity of
      the probe was characterized by a blocking study with preadministration of excess
      nonfluorescent peptide cFlFlF-PEG and by an imaging study with a scrambled
      peptide probe cLFFFL-PEG-Cy7. NIRF imaging of mice injected with cinnamoyl-L-F-F
      F-L-PEG-cyanine7 (cFlFlF-PEG-Cy7) revealed that the fluorescence intensity for
      inflamed left ears was approximately fourfold higher than that of control right
      ears at 24 hours postinjection. In comparison, the ratios acquired with the
      scrambled probe and from the blocking study were 1.5- and 2-fold at 24 hours
      postinjection, respectively. Moreover, a microscopic immunohistologic study
      confirmed that the NIRF signal of cFlFlF-PEG-Cy7 was associated with activated
      neutrophils in the inflammatory tissue. With this probe, in vivo neutrophil
      chemotaxis could be correlatively imaged macroscopically in live animals and
      microscopically at tissue and cellular levels.

PMID- 22954182
TI  - Combined in situ zymography, immunofluorescence, and staining of iron oxide
      particles in paraffin-embedded, zinc-fixed tissue sections.
AB  - Superparamagnetic iron oxide particles are used as potent contrast agents in
      magnetic resonance imaging. In histology, these particles are frequently
      visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded
      tissues. Recently, zinc salt-based fixative was shown to preserve enzyme activity
      in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation
      allows combining in situ zymography with fluorescence immunohistochemistry (IHC)
      and iron staining for advanced biologic investigation of iron oxide particle
      accumulation. Very small iron oxide particles, developed for magnetic resonance
      angiography, were applied intravenously to BALB/c nude mice. After 3 hours,
      spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut
      tissue sections were further processed to in situ zymography, IHC, and Prussian
      blue staining procedures. The combination of in situ zymography as well as IHC
      with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded
      tissues resulted in excellent histologic images of enzyme activity, protease
      distribution, and iron oxide particle accumulation. The combination of all three
      stains on a single section allowed direct comparison with only moderate
      degradation of fluorescein isothiocyanate-labeled substrate. This protocol is
      useful for investigating the biologic environment of accumulating iron oxide
      particles, with excellent preservation of morphology.

PMID- 22954183
TI  - In vivo quantitative measurement of arthritis activity based on  hydrophobically
      modified glycol chitosan in inflammatory arthritis: more active than passive 
      accumulation.
AB  - We demonstrated that arthritis could be visualized noninvasively using
      hydrophobically modified glycol chitosan nanoparticles labeled with Cy5.5 (HGC
      Cy5.5) and an optical imaging system. Activated macrophages expressing Mac-1
      molecules effectively phagocytosed HGC-Cy5.5, which formed spherical
      nanoparticles under physiologic conditions. We estimated the applicability of HGC
      Cy5.5 to quantitative analysis of arthritis development and progression. Near
      infrared fluorescence images, captured after HGC-Cy5.5 injection in mice with
      collagen-induced arthritis, showed stronger fluorescence intensity in the active
      arthritis group than in the nonarthritis group. According to the progression of
      arthritis in both collagen-induced arthritis and collagen antibody-induced
      arthritis models, total photon counts (TPCs) increased in parallel with the
      clinical arthritis index. Quantitative analysis of fluorescence after treatment
      with methotrexate showed a significant decrease in TPC in a dose-dependent
      manner. Histologic evaluation confirmed that the mechanism underlying selective
      accumulation of HGC-Cy5.5 within synovitis tissues included enhanced phagocytosis
      of the probe by Mac-1-expressing macrophages as well as enhanced permeability
      through leaky vessels. These results suggest that optical imaging of arthritis
      using HGC-Cy5.5 can provide an objective measurement of disease activity and, at
      the same time, therapeutic responses in rheumatoid arthritis.

PMID- 22954184
TI  - In vitro and in vivo characterization of three 68Ga- and 111In-labeled peptides
      for cholecystokinin receptor imaging.
AB  - Cholecystokinin (CCK) receptors are overexpressed in several human tumor types,
      such as medullary thyroid carcinomas and small cell lung cancers. Several ligands
      for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of
      these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its
      stabilized derivative, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], are suitable for
      imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo
      targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe(2)(p-CH2SO3H),
      Nle(3,6)], and DOTA-MG0, labeled with (111)In or (68)Ga, was evaluated in BALB/c
      nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and
      single-photon emission computed tomography (SPECT) and positron emission
      tomography (PET) were performed at 1 hour postinjection. All peptides
      specifically accreted in the CCK2R-expressing tumors. Both (111)In-DOTA-sCCK8 and
      (111)In-DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)] showed good tumor retention
      (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On
      PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors
      were clearly visualized with low uptake of sCCK8 peptides in the intestines.
      Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8
      peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high
      tumor uptake with low retention in the kidney and are therefore promising tracers
      for imaging of CCK2R-positive tumors.

PMID- 22954185
TI  - Tumor targeting using anti-epidermal growth factor receptor (ior egf/r3)
      immunoconjugate with a tetraaza macrocyclic agent (DO3A-EA).
AB  - Epidermal growth factor receptor (EGFR) signaling inhibition represents a highly
      promising arena for the application of molecularly targeted cancer therapies.
      EGFR conjugated metal chelates have been proposed as potential imaging agents for
      cancers that overexpress EGFR receptors. Through improved understanding of EGFR
      biology in human cancers, there is anticipation that more tumor-selective therapy
      approaches with diminished collateral normal tissue toxicity can be advanced. We
      report here on the results with a thermodynamically stable chelate, 1,4,7
      tris(carboxymethyl)-10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane (DO3A-EA)
      and anti-EGFr (ior egf/r3) conjugate to develop immunospecific imaging agent.
      Conjugation and labelling with anti-EGFr was performed using standard procedure
      and subjected to purification on size exclusion chromatography. The conjugated
      antibodies were labeled with a specific activity 20-30 mCi/mg of protein.
      Labeling efficiencies were measured by ascending paper chromatography on ITLC-SG
      strips. Radiolabeling of the immunoconjugate was found to be 98.5 +/- 0.30%.
      (99m)Tc-DO3A-EA-EGFr conjugate was studied in athymic mice bearing U-87MG, MDA-MB
      468 tumors following intravenous injection. Pharmacokinetic and biodistribution
      studies confirmed long circulation times (t(1/2)(fast)  =  45 min and t1/2(slow) 
      = 4 hours 40 min) and efficient accumulation in tumors. Biodistribution studies
      in athymic mice grafted with U-87MG human glioblastoma multiforme and Hela human
      cervical carcinoma tumors revealed significant localization of (99m)Tc-labeled
      antibodies conjugate in tumors and reduced accumulation in normal organs. This
      new chelating agent is promising for immunoscintigraphy since good tumour-to
      normal organ contrast could be demonstrated. These properties can be exploited
      for immunospecifc contrast agents in nuclear medicine and SPECT imaging.

PMID- 22954186
TI  - In vivo optical molecular imaging of matrix metalloproteinase activity following
      celecoxib therapy for colorectal cancer.
AB  - We present an optical molecular imaging approach to measure the efficacy of the
      cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumor growth rate through its
      effect on matrix metalloproteinase (MMP) activity. A xenograft model of
      colorectal cancer was generated in nude mice, which were then randomized to
      receive celecoxib versus vehicle. MMP activity was measured by an enzyme
      activatable optical molecular probe. A novel genetically engineered mouse (GEM)
      model of colorectal cancer was also used to assess celecoxib's effect on MMP
      activity, which was measured by quantitative fluorescence colonoscopy.
      Subcutaneously implanted xenograft tumors were 84% (SD 20.2%) smaller in volume
      in the treatment group versus the control group. Moreover, treated animals
      exhibited only a 7.6% (SEM 9%) increase in MMP activity versus 106% (SEM 8%) for
      untreated animals. There was an apparent linear relationship (r  =  .91) between
      measured MMP activity and tumor growth rate. Finally, in the GEM model
      experiment, treated murine tumors remained relatively unchanged in volume and MMP
      activity; however, untreated tumors grew significantly and showed an increase in
      MMP activity. This method may provide for the improved identification of patients
      for whom COX-2 inhibition therapy is indicated by allowing one to balance the
      patient's cardiovascular risk with the cancer's responsiveness to celecoxib.

PMID- 22954187
TI  - [18F]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) in prostate
      cancer: initial preclinical observations.
AB  - We hypothesized that imaging-based assessment of cellular proliferation in
      prostate cancer may improve tumor characterization. We therefore evaluated the
      biodistribution and effect of androgen on tumor uptake of the cellular
      proliferation imaging marker [(18)F]-2'-fluoro-5-methyl-1-beta-D
      arabinofuranosyluracil ((18)F-FMAU) in xenograft mouse models of human prostate
      cancer. Castrated and noncastrated athymic male mice were implanted with androgen
      independent PC3 and androgen-sensitive CWR22 human prostate cancer cells. Dynamic
      micro-positron emission tomography (PET)/computed tomography was performed for 1
      hour followed by 10-minute static scans at 2 and 3 hours. Animals were sacrificed
      after imaging for biodistribution studies and immunohistochemical staining of
      tumors for androgen receptor and Ki-67/MIB expression. (18)F-FMAU uptake was
      significantly higher in all major organs of the castrated animals in comparison
      with noncastrated mice, with the highest uptake in liver and the lowest uptake in
      muscle and bone. When compared to PC3 tumors, CWR22 xenografts showed
      significantly higher tumor to muscle (2.56 +/- 0.30 vs 1.99 +/- 0.30, p  =  .008)
      and tumor to liver (1.72 +/- 0.12 vs 1.26 +/- 0.17, p  =  .0003) uptake ratios in
      the noncastrated animal at the 3-hour time point. Androgen receptor and Ki-67/MIB
      expressions were higher in CWR22 than in PC3 xenografts. Our initial preclinical
      observations suggest that there may be an association between androgen signaling
      and thymidine metabolism and that (18)F-FMAU PET may be useful in prostate tumor
      characterization.

PMID- 22954188
TI  - A novel paramagnetic substrate for detecting myeloperoxidase activity in vivo.
AB  - Bis-phenylamides and bis-hydroxyindolamides of diethylenetriaminepentaacetic acid
      gadolinium (DTPA(Gd)) are paramagnetic reducing substrates of peroxidases that
      enable molecular imaging of peroxidase activity in vivo. Specifically, gadolinium
      chelates of bis-5-hydroxytryptamide-DTPA (bis-5HT-DTPA(Gd)) have been used to
      image localized inflammation in animal models by detecting neutrophil-derived
      myeloperoxidase (MPO) activity at the inflammation site. However, in other
      preclinical disease models, bis-5HT-DTPA(Gd) presents technical challenges due to
      its limited solubility in vivo. Here we report a novel MPO-sensing probe obtained
      by replacing the reducing substrate serotonin (5-HT) with 5-hydroxytryptophan
      (HTrp). Characterization of the resulting probe (bis-HTrp-DTPA(Gd)) in vitro
      using nuclear magnetic resonance spectroscopy and enzyme kinetic analysis showed
      that bis-HTrp-DTPA(Gd) (1) improves solubility in water; (2) acts as a substrate
      for both horseradish peroxidase and MPO enzymes; (3) induces cross-linking of
      proteins in the presence of MPO; (4) produces oxidation products, which bind to
      plasma proteins; and (5) unlike bis-5HT-DTPA(Gd), does not follow first-order
      reaction kinetics. In vivo magnetic resonance imaging (MRI) in mice demonstrated
      that bis-HTrp-DTPA(Gd) was retained for up to 5 days in MPO-containing sites and
      cleared faster than bis-5HT-DTPA(Gd) from MPO-negative sites. Bis-HTrp-DTPA(Gd)
      should offer improvements for MRI of MPO-mediated inflammation in vivo,
      especially in high-field MRI, which requires a higher dose of contrast agent.

PMID- 22954189
TI  - Solea senegalensis vasa transcripts: molecular characterisation, tissue
      distribution and developmental expression profiles.
AB  - The Vasa protein is an RNA helicase belonging the DEAD (Asp-Glu-Ala-Asp)-box
      family. The crucial role played by the vasa gene in the germ-cell lineage of both
      vertebrates and invertebrates has made this gene a useful molecular marker for
      germinal cells and a useful tool in surrogate broodstock production using
      primordial germ cell transplantation. With the aim of establishing a novel
      approach to improving Solea senegalensis broodstock management, the vasa gene in
      this species was characterised. Four S. senegalensis vasa transcripts were
      isolated: Ssvasa1, Ssvasa2, Ssvasa3 and Ssvasa4. Their phylogenetic relationship
      with other vasa homologues was determined confirming the high degree of
      conservation of this helicase throughout evolution. Our qPCR results showed that
      S. senegalensis vasa transcripts are prevalently expressed in gonads, with ovary
      specific expression for Ssvasa3 and Ssvasa4. During embryonic and larval
      development, a switch between the longest and the shortest transcripts was
      observed. While Ssvasa1 and Ssvasa2 were maternally supplied, Ssvasa3 and Ssvasa4
      depended on the de novo expression program of the growing juveniles, suggesting
      that vasa mRNA could be involved in Senegalese sole gonad differentiation. In
      situ hybridisation and immunohistochemical analysis performed in 150-days after
      hatching (DAH) larvae showed vasa product expression in the germinal region of
      early gonads. In our work we demonstrated the usefulness of Ssvasa mRNAs as
      molecular markers for primordial germ cells and germinal cells during embryonic
      development, larval ontogenesis and gonad differentiation. Furthermore, our
      results confirmed the potential of vasa to help investigate germinal cell
      biotechnology for Senegalese sole reproduction.

PMID- 22954190
TI  - Osteoarthritis--the forgotten chronic disease. Time for a multimorbid approach?

PMID- 22954191
TI  - Normalizing HIV testing in primary care. Commentary on: Late HIV diagnoses in
      Europe: a call for increased testing and awareness among general practitioners.

PMID- 22954192
TI  - Termination of pregnancy: attitudes and clinical experiences of Irish GPs and GPs
      in-training.
AB  - BACKGROUND: Termination of pregnancy (ToP) is currently illegal in Ireland. In
      2010, more than 4000 women travelled from Ireland to the UK for a ToP.
      OBJECTIVES: The aims of this study were to assess the attitudes and clinical
      experiences of Irish General Practitioners (GPs) and GPs-in-training (GPRs)
      towards ToP. METHODS: A postal survey was sent to 500 GPs in Ireland. An internet
      based survey was sent to 244 GPRs. Quantitative and qualitative analysis was
      performed. RESULTS: Overall response was 44%. Four groups of doctor's opinions
      could be identified: (A) abortion can never be allowed (10%); (B) abortion can be
      allowed in limited circumstances (25%); (C) abortion should be available to all
      women (51%); and (D) no definite opinion (14%). Doctors in groups (A) and (B)
      were older and more often Catholic. Of doctors in group (C), 66% indicated an
      upper gestational limit of maximum 16 weeks. More than 40% of all respondents had
      at least one consultation specifically dealing with ToP within the past six
      months and 43% agreed with the statement that women's health suffers due to the
      travel related to ToP. CONCLUSION: Most responding GPs and GPRs (75%) support the
      provision of ToP in Ireland in certain circumstances. The qualitative analysis of
      this survey showed that the terms pro-life and pro-choice inappropriately
      describe the spectrum of opinions. This study highlights clinical situations in
      which women's health may be adversely affected due to the requirement to travel
      for ToP.

PMID- 22954193
TI  - Acceptance of preventive treatment in migraine patients: results of a survey.
AB  - BACKGROUND: The number of migraine patients eligible for preventive treatment is
      considerably higher than the number of patients actually using it. This study
      explores reasons for this discrepancy. METHODS: An explorative survey among
      patients and their general practitioners (GPs) participating in a trial on
      preventive medication. Migraine patients who were eligible for preventive
      treatment (n = 75) attended an evaluation consultation with their GP to optimize
      migraine treatment. GPs and patients who did not start preventive treatment were
      asked if they had discussed the possibility of preventive treatment and, if so,
      why they decided not to start it. RESULTS: Of the 32 GPs, 8 (25%) did not discuss
      the possibility of preventive treatment with their patients; in 4 because of
      perceived lack of effectiveness. Patients who did not start preventive treatment
      (n = 43) used less triptans and had less psychological distress compared to those
      who did start (n = 32). Main reasons for patients not starting were negative
      attitudes towards medication in general, fear of medication side-effects,
      previous unsuccessful attempts, attacks not being severe enough, and impact of
      migraine on daily life acceptable. CONCLUSION: The decision of the individual
      patient and their GP to start preventive treatment is not only determined by
      attack frequency, but also depends on the impact of the headache attacks on their
      daily life and their negative attitude towards medication.

PMID- 22954194
TI  - Isolated headache in general practice: determinants for delay in referral in
      patients with subarachnoid haemorrhage.
AB  - BACKGROUND: A delay in diagnosing aneurismal subarachnoid haemorrhage (SAH)
      occurs in a substantial proportion of patients who present with headache as the
      only symptom. OBJECTIVE: To identify determinants for a delay in referral in
      patients with SAH, who present with isolated headache to the general practitioner
      (GP). METHODS: For all 112 patients with SAH admitted to the hospital between
      October 2008 and June 2009, we sent a questionnaire to the GPs asking for details
      presented during the initial GP visit. In this retrospective study, we included
      31 patients with SAH who initially presented with isolated headache. We assessed
      acuteness of headache onset, history of headaches and a patient delay as
      determinants for delayed referral (> 2 h after a visit to the GP), by calculating
      risk ratios (RRs) with corresponding 95% confidence intervals (CIs). RESULTS:
      Referral was delayed in 18 of these 31 patients. The delay occurred in all 10
      patients in whom the GP was unaware of the acute onset of headache and in 8 of 21
      patients in whom the GP was aware of this symptom (RR: 2.6; 95% CI: 1.5-4.5). A
      history of headaches (RR: 1.8; 95% CI: 1.1-3.0) and a patient delay (RR: 2.1; 95%
      CI: 1.0-4.5) also increased the probability of delayed referral. CONCLUSION: In
      patients with SAH who presented with isolated headache to the GP, GP's
      unawareness of the acute onset of the headache, a history of headaches and late
      presentation by the patient increased the probability of delayed referral.

PMID- 22954198
TI  - Primary care at times of the economic crisis.

PMID- 22954200
TI  - Coplanar-gate transparent graphene transistors and inverters on plastic.
AB  - Transparent flexible graphene transistors and inverters in a coplanar-gate
      configuration were presented for the first time using only two materials:
      graphene and an ion gel gate dielectric. The novel device configuration
      simplifies device fabrication such that only two printing steps were required to
      fabricate transistors and inverters. The devices exhibited excellent device
      performances including low-voltage operation with a high transistor-on-current
      and mobility, excellent mechanical flexibility, environmental stability, and a
      reasonable inverting behavior upon connecting the two transistors.

PMID- 22954201
TI  - Olmesartan/amlodipine combination versus olmesartan or amlodipine monotherapies
      on blood pressure and insulin resistance in a sample of hypertensive patients.
AB  - Despite the wide range of antihypertensive medications, about 45.5% of treated
      patients fail to achieve the desired blood pressure (BP) target. This study
      evaluated the effects of an olmesartan/amlodipine single pill combination
      compared to olmesartan or amlodipine monotherapies on BP, lipid profile, insulin
      resistance, and insulin sensitivity parameters. Two hundred and seventy-six
      patients were randomly assigned to olmesartan (20 mg), amlodipine (10 mg), or a
      single pill containing olmesartan/amlodipine (5/20 mg) for 12 months. We
      evaluated the following parameters at the baseline, and after 6 and 12 months:
      body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP
      and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), and lipid
      profile. At the baseline, and after 6 and 12 months, patients underwent an
      euglycemic, hyperinsulinemic clamp to assess M value. Olmesartan/amlodipine gave
      a greater decrease in SBP and DPB compared to amlodipine and olmesartan at 6 (P <
      .05) and 12 months (P < .01). There was a decrease in FPG with
      olmesartan/amlodipine after 12 months compared to amlodipine (P < .05).
      Olmesartan/amlodipine decreased FPI and homeostasis model assessment index
      compared to both baseline (P < .05) and olmesartan and amlodipine (P < .05).
      Olmesartan/amlodipine gave an increase in M value, compared to baseline (P < .01)
      and to olmesartan monotherapy (P < .05) and amlodipine monotherapy (P < .01). In
      this randomized, double-blind clinical trial, olmesartan/amlodipine combination
      resulted more effective than olmesartan and amlodipine monotherapies in reducing
      BP, in improving insulin resistance, and insulin sensitivity parameters in
      patients with stage I essential hypertension. The combination also resulted in
      less peripheral edema. 

PMID- 22954202
TI  - Determination of ochratoxin A in wine by means of immunoaffinity and aminopropyl
      solid-phase column cleanup and fluorometric detection.
AB  - A new analytical method for the determination of ochratoxin A (OTA) in red wine
      has been developed by using a double-extract cleanup and a fluorometric
      measurement after spectral deconvolution. Wine samples were diluted with a
      solution containing 1% polyethylene glycol and 5% sodium hydrogencarbonate,
      filtered, and purified by immunoaffinity and aminopropyl solid-phase column. OTA
      contents in the purified extract were determined by a spectrofluorometer
      (excitation wavelength, 330 nm; emission wavelength, 470 nm) after deconvolution
      of fluorescence spectra. Average recoveries from wine samples spiked with OTA at
      levels ranging from 0.5 to 3.0 ng/mL were 94.5-105.4% with relative standard
      deviations (RSD) of <15% (n = 4). The limit of detection (LOD) was 0.2 ng/mL, and
      the total time of analysis was 30 min. The developed method was tested on 18 red
      wine samples (naturally contaminated and spiked with OTA at levels ranging from
      0.4 to 3.0 ng/mL) and compared with AOAC Official Method 2001.01, based on
      immunoaffinity column cleanup and HPLC with fluorescence detector. A good
      correlation (r(2) = 0.9765) was observed between OTA levels obtained with the two
      methods, highlighting the reliability of the proposed method, the main advantage
      of which is the simple OTA determination by a benchtop fluorometer with evident
      reductions of cost and time of analysis.

PMID- 22954203
TI  - Local environmental pollution strongly influences culturable bacterial aerosols
      at an urban aquatic superfund site.
AB  - In polluted environments, when microbial aerosols originate locally, species
      composition of the aerosols should reflect the polluted source. To test the
      connection between local environmental pollution and microbial aerosols near an
      urban waterfront, we characterized bacterial aerosols at Newtown Creek (NTC), a
      public waterway and Superfund site in a densely populated area of New York, NY,
      USA. Culturable bacterial aerosol fallout rate and surface water bacterial
      concentrations were at least an order of magnitude greater at NTC than at a
      neighboring, less polluted waterfront and a nonurban coastal site in Maine. The
      NTC culturable bacterial aerosol community was significantly different in
      taxonomic structure from previous urban and coastal aerosol studies, particularly
      in relative abundances of Actinobacteria and Proteobacteria. Twenty-four percent
      of the operational taxonomic units in the NTC overall (air + water) bacterial
      isolate library were most similar to bacterial 16S rRNA gene sequences previously
      described in terrestrial or aquatic environments contaminated with sewage,
      hydrocarbons, heavy metals, and other industrial waste. This study is the first
      to examine the community composition and local deposition of bacterial aerosols
      from an aquatic Superfund site. The findings have important implications for the
      use of aeration remediation in polluted aquatic environments and suggest a novel
      pathway of microbial exposure in densely populated urban communities containing
      contaminated soil and water.

PMID- 22954205
TI  - Population-based study on prognostic factors for recurrence and progression in
      primary stage T1 bladder tumours.
AB  - OBJECTIVE: Stage T1 urothelial carcinoma of the bladder (UCB) exhibits
      heterogeneous clinical behaviour, and the treatment is controversial. The aim of
      this study was to evaluate prognostic factors for UCB in a defined, population
      based cohort comprising patients with a first time diagnosis of primary stage T1
      UCB. MATERIAL AND METHODS: The study population initially consisted of 285
      patients with primary stage T1 UCB reported to the regional Bladder Cancer
      Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The
      histological specimens were re-evaluated concerning stage, substaging of T1,
      World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour
      volume and total resected volume. Hospital records provided data on tumour size
      and multiplicity, occurrence of possible relapse and/or progression, death from
      UCB and whether treatment was given. RESULTS: After re-evaluation, the study
      population comprised 211 patients. The median follow-up time was 60 months. LVI
      was a prognostic factor for UCB progression and recurrence. Tumour size larger
      than 30 mm and multiplicity increased the risk of recurrence. T1 substaging,
      tumour volume and total resected volume were not associated with recurrence or
      tumour progression. CONCLUSIONS: LVI is significantly correlated with progression
      and recurrence in patients with primary stage T1 UCB. Therefore, the presence of
      LVI should be evaluated in every new case of T1 UCB.

PMID- 22954204
TI  - Systematic comparison of reverse phase and hydrophilic interaction liquid
      chromatography platforms for the analysis of N-linked glycans.
AB  - Due to the hydrophilic nature of glycans, reverse phase chromatography has not
      been widely used as a glycomic separation technique coupled to mass spectrometry.
      Other approaches such as hydrophilic interaction chromatography and porous
      graphitized carbon chromatography are often employed, though these strategies
      frequently suffer from decreased chromatographic resolution, long equilibration
      times, indefinite retention, and column bleed. Herein, it is shown that, through
      an efficient hydrazone formation derivatization of N-linked glycans (~4 h of
      additional sample preparation time which is carried out in parallel), numerous
      experimental and practical advantages are gained when analyzing the glycans by
      online reverse phase chromatography. These benefits include an increased number
      of glycans detected, increased peak capacity of the separation, and the ability
      to analyze glycans on the identical liquid chromatography-mass spectrometry
      platform commonly used for proteomic analyses. The data presented show that
      separation of derivatized N-linked glycans by reverse phase chromatography
      significantly out-performs traditional separation of native or derivatized
      glycans by hydrophilic interaction chromatography. Furthermore, the movement to a
      more ubiquitous separation technique will afford numerous research groups the
      opportunity to analyze both proteomic and glycomic samples on the same platform
      with minimal time and physical change between experiments, increasing the
      efficiency of "multiomic" biological approaches.

PMID- 22954206
TI  - A novel multiplex-protein array for serum diagnostics of colon cancer: a case
      control study.
AB  - BACKGROUND: More than 1.2 million new cases of colorectal cancer are reported
      each year worldwide. Despite actual screening programs, about 50% of the patients
      are diagnosed at advanced tumor stages presenting poor prognosis. Innovative
      screening tools could aid the detection at early stages and allow curative
      treatment interventions. METHODS: A nine target multiplex serum protein biochip
      was generated and evaluated using a training- and validation-set of 317 highly
      standardized, liquid nitrogen preserved serum samples comprising controls,
      adenomas, and colon cancers. RESULTS: Serum levels of CEA, IL-8, VEGF, S100A11,
      MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and
      controls. The largest areas under the receiver operating characteristics curve
      were observed for CEA, IL-8, and CRP. At threshold levels yielding 90%
      specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%,
      respectively. The most promising marker combinations were CEA + IL-8 reaching 37%
      sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81%
      specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity
      at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity.
      Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for
      CEA + CRP. CONCLUSIONS: Apart from CEA, IL-8, and CRP, the screening value of
      additional blood markers and the potential advantage of combining serum biochip
      testing with fecal occult blood testing needs to be studied. Multiplex biochip
      array technology utilizing serum samples offers an innovative approach to
      colorectal cancer screening.

PMID- 22954207
TI  - Solving the convergence problem in the synthesis of triantennary N-glycan
      relevant to prostate-specific membrane antigen (PSMA).
AB  - The first total synthesis of triantennary, fully sialylated N-glycan of complex
      type is described. Two strategies for installation of sialylated antennae are
      explored, and both approaches converge on a global glycosylation step that
      delivers the desired tetradecasaccharide in good yields.

PMID- 22954208
TI  - Emerging concepts: from coeliac disease to non-coeliac gluten sensitivity.
AB  - The rise in gluten consumption over time has led to the increasing recognition of
      coeliac disease (CD) with associated complications. However, only recently has
      there been an appreciation that the spectrum of gluten-related disorders is
      greater than just CD, which may explain the growing global popularity in gluten
      free products. Current literature suggests that a newly recognised clinical
      entity in the form of non-coeliac gluten sensitivity (NCGS) may be the most
      common gluten-related disorder encountered by healthcare professionals, although
      its exact prevalence is as yet unknown. This article will review the historical
      relationship between mankind and gluten as well as the progressive recognition
      that it is possible for gluten to have a deleterious effect on our health. To
      this effect we discuss the prevalence, diagnosis and complications of CD
      including the benefits derived from a gluten-free diet (GFD). Finally, we discuss
      our current understanding of NCGS, in addition to highlighting the need for
      further research to determine the extent, clinicopathological features and
      serological biomarkers to help recognise this emerging condition in clinical
      practice.

PMID- 22954209
TI  - Overview of the creative genome: effects of genome structure and sequence on the
      generation of variation and evolution.
AB  - This overview of a special issue of Annals of the New York Academy of Sciences
      discusses uneven distribution of distinct types of variation across the genome,
      the dependence of specific types of variation upon distinct classes of DNA
      sequences and/or the induction of specific proteins, the circumstances in which
      distinct variation-generating systems are activated, and the implications of this
      work for our understanding of evolution and of cancer. Also discussed is the
      value of non text-based computational methods for analyzing information carried
      by DNA, early insights into organizational frameworks that affect genome
      behavior, and implications of this work for comparative genomics.

PMID- 22954210
TI  - Genome hyperevolution and the success of a parasite.
AB  - The strategy of antigenic variation is to present a constantly changing
      population phenotype that enhances parasite transmission, through evasion of
      immunity arising within, or existing between, host animals. Trypanosome antigenic
      variation occurs through spontaneous switching among members of a silent archive
      of many hundreds of variant surface glycoprotein (VSG) antigen genes. As with
      such contingency systems in other pathogens, switching appears to be triggered
      through inherently unstable DNA sequences. The archive occupies subtelomeres, a
      genome partition that promotes hypermutagenesis and, through telomere position
      effects, singular expression of VSG. Trypanosome antigenic variation is augmented
      greatly by the formation of mosaic genes from segments of pseudo-VSG, an example
      of implicit genetic information. Hypermutation occurs apparently evenly across
      the whole archive, without direct selection on individual VSG, demonstrating
      second-order selection of the underlying mechanisms. Coordination of antigenic
      variation, and thereby transmission, occurs through networking of trypanosome
      traits expressed at different scales from molecules to host populations.

PMID- 22954211
TI  - The tricky path to recombining X and Y chromosomes in meiosis.
AB  - Sex chromosomes are the Achilles' heel of male meiosis in mammals. Mis
      segregation of the X and Y chromosomes leads to sex chromosome aneuploidies, with
      clinical outcomes such as infertility and Klinefelter syndrome. Successful
      meiotic divisions require that all chromosomes find their homologous partner and
      achieve recombination and pairing. Sex chromosomes in males of many species have
      only a small region of homology (the pseudoautosomal region, PAR) that enables
      pairing. Until recently, little was known about the dynamics of recombination and
      pairing within mammalian X and Y PARs. Here, we review our recent findings on PAR
      behavior in mouse meiosis. We uncovered unexpected differences between autosomal
      chromosomes and the X-Y chromosome pair, namely that PAR recombination and
      pairing occurs later, and is under different genetic control. These findings
      imply that spermatocytes have evolved distinct strategies that ensure successful
      X-Y recombination and chromosome segregation.

PMID- 22954213
TI  - The genome: an isochore ensemble and its evolution.
AB  - The genomes of eukaryotes are mosaics of isochores. These are long DNA stretches
      that are fairly homogeneous in base composition and that belong to a small number
      of families characterized by different ratios of GC to AT and different short
      sequence patterns (i.e., different DNA structures that interact with different
      proteins). This genome organization led to two discoveries: (1) the genomic code,
      which refers to two correlations, that of the composition of coding and
      contiguous noncoding sequences, and that of coding sequences and the structural
      properties of the encoded proteins; and (2) the genome phenotypes, which
      correspond to the patterns of isochore families in the genomes. These patterns
      indicate that genome evolution may proceed either according to a conservative
      mode or to a transitional (isochore shifting) mode, apparently depending upon
      whether the environment is constant or shifting. According to the neoselectionist
      theory, natural selection is responsible for both modes.

PMID- 22954214
TI  - Multiple levels of meaning in DNA sequences, and one more.
AB  - If we define a genetic code as a widespread DNA sequence pattern that carries a
      message with an impact on biology, then there are multiple genetic codes.
      Sequences involved in these codes overlap and, thus, both interact with and
      constrain each other, such as for the triplet code, the intron-splicing code, the
      code for amphipathic alpha helices, and the chromatin code. Nucleosomes
      preferentially are located at the ends of exons, thus protecting splice
      junctions, with the N9 positions of guanines of the GT and AG junctions oriented
      toward the histones. Analysis of protein-coding sequences reveals numerous traces
      of tandem repeats, apparently formed by triplet expansion, which in effect is a
      genome inflation ''code''. Our data are consistent with the hypothesis that
      expansion of simple tandem repetition of certain aggressive triplets has been a
      characteristic of life from its emergence. Such expanding triplets appear to be
      the major factor underlying observed codon usage biases.

PMID- 22954212
TI  - Sites of genetic instability in mitosis and cancer.
AB  - Certain chromosomal regions called common fragile sites are prone to difficulty
      during replication. Many tumors have been shown to contain alterations at fragile
      sites. Several models have been proposed to explain why these sites are unstable.
      Here we describe work to investigate models of fragile site instability using a
      yeast artificial chromosome carrying human DNA from a common fragile site region.
      In addition, we describe a yeast system to investigate whether repair of breaks
      at a naturally occurring fragile site in yeast, FS2, involves mitotic
      recombination between homologous chromosomes, leading to loss of heterozygosity
      (LOH). Our initial evidence is that repair of yeast fragile site breaks does lead
      to LOH, suggesting that human fragile site breaks may similarly contribute to LOH
      in cancer. This work is focused on gaining understanding that may enable us to
      predict and prevent the situations and environments that promote genetic changes
      that contribute to tumor progression.

PMID- 22954215
TI  - Evolution of simple sequence repeat-mediated phase variation in bacterial
      genomes.
AB  - Mutability as mechanism for rapid adaptation to environmental challenge is an
      alluringly simple concept whose apotheosis is realized in simple sequence repeats
      (SSR). Bacterial genomes of several species contain SSRs with a proven role in
      adaptation to environmental fluctuations. SSRs are hypermutable and generate
      reversible mutations in localized regions of bacterial genomes, leading to phase
      variable ON/OFF switches in gene expression. The application of genetic,
      bioinformatic, and mathematical/computational modeling approaches are
      revolutionizing our current understanding of how genomic molecular forces and
      environmental factors influence SSR-mediated adaptation and led to evolution of
      this mechanism of localized hypermutation in bacterial genomes.

PMID- 22954216
TI  - Indirect selection of implicit mutation protocols.
AB  - A hypothesis that mutability evolves to facilitate evolutionary adaptation is
      dismissed by many biologists. Their skepticism is based on a theoretical
      expectation that natural selection must minimize mutation rates. That view, in
      turn, is historically grounded in an intuitive presumption that "the vast
      majority of mutations are harmful." But such skepticism is surely misplaced.
      Several highly mutagenic genomic patterns, including simple sequence repeats, and
      transposable elements, are integrated into an unexpectedly large proportion of
      functional genetic loci. Because alleles arising within such patterns can retain
      an intrinsic propensity toward a particular style of mutation, natural selection
      that favors any such allele can indirectly favor the site's mutability as well.
      By exploiting patterns that have produced beneficial alleles in the past,
      indirect selection can encourage mutation within constraints that reduce the
      probability of deleterious effect, thereby shaping implicit "mutation protocols"
      that effectively promote evolvability.

PMID- 22954217
TI  - G4 motifs in human genes.
AB  - The G4 motif, G(>=3) N(x) G(>=3) N(x) G(>=3) N(x) G(>=3) , is enriched in some
      genomic regions and depleted in others. This motif confers the ability to form an
      unusual four-stranded DNA structure, G4 DNA. G4 DNA is associated with genomic
      instability, which may explain depletion of G4 motifs from some genes and genomic
      regions. Conversely, G4 motifs are enriched downstream of transcription start
      sites, where they correlate with pausing. The uneven distribution of G4 motifs in
      the genome strongly suggests that mechanisms of selection act not only on one
      dimensional genomic sequence, but also on structures formed by genomic DNA. The
      biological roles of G4 structures illustrate that, to understand genome function,
      it is important to consider the dynamic structural potential implicit in the G4
      motif.

PMID- 22954219
TI  - Integrons and gene cassettes: hotspots of diversity in bacterial genomes.
AB  - Integrons are genetic units found in many bacterial species that are defined by
      their ability to capture small mobile elements called gene cassettes. Cassettes
      usually contain only one gene, potentially any gene, and an attC recombination
      site, and thousands of cassettes have been sequenced. A specialized IntI site
      specific recombinase encoded by the integron recognizes attC and incorporates
      cassettes into an attI site located adjacent to the intI gene. Over 100 types of
      integrons have been found, most in bacterial chromosomes. They can all
      potentially share the same cassettes and, as recombination between attC in a
      cassette and an attI can occur repeatedly, an integron can contain from zero to
      hundreds of cassettes. Cassette arrays that are not located next to an intI gene,
      or solo cassettes at apparently random sites, are also seen. Hence, integrons
      contribute to generation of diversity in bacterial, plasmid, and transposon
      genomes and facilitate extensive sharing of information among bacteria.

PMID- 22954218
TI  - Adaptive radiation of venomous marine snail lineages and the accelerated
      evolution of venom peptide genes.
AB  - An impressive biodiversity (>10,000 species) of marine snails (suborder
      Toxoglossa or superfamily Conoidea) have complex venoms, each containing
      approximately 100 biologically active, disulfide-rich peptides. In the genus
      Conus, the most intensively investigated toxoglossan lineage (~500 species), a
      small set of venom gene superfamilies undergo rapid sequence hyperdiversification
      within their mature toxin regions. Each major lineage of Toxoglossa has its own
      distinct set of venom gene superfamilies. Two recently identified venom gene
      superfamilies are expressed in the large Turridae clade, but not in Conus. Thus,
      as major venomous molluscan clades expand, a small set of lineage-specific venom
      gene superfamilies undergo accelerated evolution. The juxtaposition of extremely
      conserved signal sequences with hypervariable mature peptide regions is
      unprecedented and raises the possibility that in these gene superfamilies, the
      signal sequences are conserved as a result of an essential role they play in
      enabling rapid sequence evolution of the region of the gene that encodes the
      active toxin.

PMID- 22954220
TI  - Creative deaminases, self-inflicted damage, and genome evolution.
AB  - Organisms minimize genetic damage through complex pathways of DNA repair. Yet a
      gene family--the AID/APOBECs--has evolved in vertebrates with the sole purpose of
      producing targeted damage in DNA/RNA molecules through cytosine deamination. They
      likely originated from deaminases involved in A>I editing in tRNAs. AID, the
      archetypal AID/APOBEC, is the trigger of the somatic diversification processes of
      the antibody genes. Its homologs may have been associated with the immune system
      even before the evolution of the antibody genes. The APOBEC3s, arising from
      duplication of AID, are involved in the restriction of exogenous/endogenous
      threats such as retroviruses and mobile elements. Another family member, APOBEC1,
      has (re)acquired the ability to target RNA while maintaining its ability to act
      on DNA. The AID/APOBECs have shaped the evolution of vertebrate genomes, but
      their ability to mutate nucleic acids is a double-edged sword: AID is a key
      player in lymphoproliferative diseases by triggering mutations and chromosomal
      translocations in B cells, and there is increasing evidence suggesting that other
      AID/APOBECs could be involved in cancer development as well.

PMID- 22954221
TI  - Three-dimensional architecture of the IgH locus facilitates class switch
      recombination.
AB  - Immunoglobulin (Ig) class switch recombination (CSR) is responsible for
      diversification of antibody effector function during an immune response. This
      region-specific recombination event, between repetitive switch (S) DNA elements,
      is unique to B lymphocytes and is induced by activationinduced deaminase (AID).
      CSR is critically dependent on transcription of noncoding RNAs across S regions.
      However, mechanistic insight regarding this process has remained unclear. New
      studies indicate that long-range intrachromosomal interactions among IgH
      transcriptional elements organize the formation of the S/S synaptosome, as a
      prerequisite for CSR. This three-dimensional chromatin architecture
      simultaneously brings promoters and enhancers into close proximity to facilitate
      transcription. Here, we recount how transcription across S DNA promotes
      accumulation of RNA polymerase II, leading to the introduction of activating
      chromatin modifications and hyperaccessible chromatin that is amenable to AID
      activity.

PMID- 22954222
TI  - Preaching about the converted: how meiotic gene conversion influences genomic
      diversity.
AB  - Meiotic crossover (CO) recombination involves a reciprocal exchange between
      homologous chromosomes. COs are often associated with gene conversion at the
      exchange site where genetic information is unidirectionally transferred from one
      chromosome to the other. COs and independent assortment of homologous chromosomes
      contribute significantly to the promotion of genomic diversity. What has not been
      appreciated is the contribution of another product of meiotic recombination,
      noncrossovers (NCOs), which result in gene conversion without exchange of
      flanking markers. Here, we review our comprehensive analysis of recombination at
      a highly polymorphic mouse hotspot. We found that NCOs make up ~90% of
      recombination events. Preferential recombination initiation on one chromosome
      allowed us to estimate the contribution of CO and NCO gene conversion to
      transmission distortion, a deviation from Mendelian inheritance in the
      population. While NCO gene conversion tracts are shorter, and thus have a more
      punctate effect, their higher frequency translates into an approximately two-fold
      greater contribution than COs to gene conversion-based allelic shuffling and
      transmission distortion. We discuss the potential impact of mammalian NCO
      characteristics on evolution and genomic diversity.

PMID- 22954223
TI  - Gross chromosomal rearrangement mediated by DNA replication in stressed cells:
      evidence from Escherichia coli.
AB  - Gross chromosomal rearrangements (GCRs), or changes in chromosome structure, play
      central roles in evolution and are central to cancer formation and progression.
      GCRs underlie copy number variation (CNV), and therefore genomic disorders that
      stem from CNV. We study amplification in Escherichia coli as a model system to
      understand mechanisms and circumstances of GCR formation. Here, we summarize
      observations that led us to postulate that GCR occurs by a replicative mechanism
      as part of activated stress responses. We report that we do not find RecA to be
      downregulated by stress on a population basis and that constitutive expression of
      RecA does not inhibit amplification, as would be expected if downregulation of
      RecA made cells permissive for nonhomologous recombination. Strains deleted for
      the genes for three proteins that inhibit RecA activity, psiB, dinI, and recX,
      all show unaltered amplification, suggesting that if they do downregulate RecA
      indirectly, this activity does not promote amplification.

PMID- 22954224
TI  - Implications of genetic heterogeneity in cancer.
AB  - DNA sequencing studies have established that many cancers contain tens of
      thousands of clonal mutations throughout their genomes, which is difficult to
      reconcile with the very low rate of mutation in normal human cells. This
      observation provides strong evidence for the mutator phenotype hypothesis, which
      proposes that a genome-wide elevation in the spontaneous mutation rate is an
      early step in carcinogenesis. An elevated mutation rate implies that cancers
      undergo continuous evolution, generating multiple subpopulations of cells that
      differ from one another in DNA sequence. The extensive heterogeneity in DNA
      sequence and continual tumor evolution that would occur in the context of a
      mutator phenotype have important implications for cancer diagnosis and therapy.

PMID- 22954225
TI  - Experimental and theoretical charge density study of the chemical bonding in
      chlorokojic acid crystal structure.
AB  - The experimental charge density in the chlorokojic acid crystal structure was
      investigated on the basis of high-resolution X-ray diffraction data collected at
      80(2) K. The nature of chemical bonding and halogen interactions has been studied
      by means of deformation densities and by topological analysis using the Bader's
      quantum theory of atoms in molecules (QTAIM). A comparison between the
      experimental and theoretical results, from calculations concerning gas phase and
      periodic DFT/B3LYP, was performed. For the intermolecular hydrogen bonds of O
      H...O, C-H...O, and C-H...Cl types, full characteristics of bond critical points
      (BCP's) were provided indicating closed-shell interactions. The topological
      analysis of charge density distribution revealed the presence of intermolecular C
      Cl...O halogen bridge and halogen-halogen interactions of C-Cl...Cl-C type
      forming supramolecular Cl(3) synthons, crucial for three-dimensional structure
      formation of chlorokojic acid. The pronounced anisotropy of electrostatic
      potential at the Cl atom clarifies both electrophilic and nucleophilic properties
      of the substituent.

PMID- 22954226
TI  - Prehospital point-of-care testing for troponin: are the results reliable?
AB  - BACKGROUND: Swift assessment of patients presenting with chest pain results in
      faster treatment and improved outcomes. Allowing ambulance crews to use point-of
      care (POC) devices to measure cardiac troponin I levels during transport of
      patients to the emergency department (ED) may result in earlier diagnosis of
      acute myocardial infarction, particularly in those patients without ST-segment
      elevation. The ability of POC devices to measure cardiac troponin I levels
      reliably in a moving ambulance has not previously been tested. Objective. This
      study was conducted to determine whether POC devices operated in a moving
      ambulance reliably duplicate the measurement of cardiac troponin I levels
      obtained by POC devices in the ED. METHODS: Blood samples were obtained in the ED
      and the hospital from patients reporting chest pain or other cardiac complaints.
      Troponin I assays were then performed in a moving ambulance using two POC
      devices. The POC devices were placed on flat surfaces in the rear of the
      ambulance. The ambulance driver was instructed to keep the ambulance moving in
      traffic while each assay was completed. A variety of routes were taken. Each set
      of two assays was completed entirely during a single simulated run. The results
      of the two assays performed in the moving ambulance were then compared with the
      results of the control assay, which was performed simultaneously in the ED on the
      same sample. RESULTS: Forty-two whole-blood samples underwent troponin I assays
      in a moving ambulance. Thirteen (30.9%) assays were positive. One (2.4%) was
      excluded because of cartridge error. Two (4.8%) were excluded because of
      interfering substance. No significant difference in whole-blood troponin results
      was found between the assays performed in the moving ambulance and those
      performed in the ED (intraclass correlation coefficient 0.997; 95% confidence
      interval 0.994 to 0.998; p < 0.005). CONCLUSIONS: When used in a moving
      ambulance, the POC device provided results of cardiac troponin I assays that were
      highly correlated to the results when the device was used in the ED. The
      feasibility, practicality, and clinical utility of prehospital use of POC devices
      must still be assessed. Key words: point-of-care systems; prehospital emergency
      care; troponin; reliability of results; ambulances; myocardial infarction; chest
      pain.

PMID- 22954227
TI  - Cytosolic re-localization and optimization of valine synthesis and catabolism
      enables inseased isobutanol production with the yeast Saccharomyces cerevisiae.
AB  - BACKGROUND: The branched chain alcohol isobutanol exhibits superior
      physicochemical properties as an alternative biofuel. The yeast Saccharomyces
      cerevisiae naturally produces low amounts of isobutanol as a by-product during
      fermentations, resulting from the catabolism of valine. As S. cerevisiae is
      widely used in industrial applications and can easily be modified by genetic
      engineering, this microorganism is a promising host for the fermentative
      production of higher amounts of isobutanol. RESULTS: Isobutanol production could
      be improved by re-locating the valine biosynthesis enzymes Ilv2, Ilv5 and Ilv3
      from the mitochondrial matrix into the cytosol. To prevent the import of the
      three enzymes into yeast mitochondria, N-terminally shortened Ilv2, Ilv5 and Ilv3
      versions were constructed lacking their mitochondrial targeting sequences. SDS
      PAGE and immunofluorescence analyses confirmed expression and re-localization of
      the truncated enzymes. Growth tests or enzyme assays confirmed enzymatic
      activities. Isobutanol production was only increased in the absence of valine and
      the simultaneous blockage of the mitochondrial valine synthesis pathway.
      Isobutanol production could be even more enhanced after adapting the codon usage
      of the truncated valine biosynthesis genes to the codon usage of highly expressed
      glycolytic genes. Finally, a suitable ketoisovalerate decarboxylase, Aro10, and
      alcohol dehydrogenase, Adh2, were selected and overexpressed. The highest
      isobutanol titer was 0.63 g/L at a yield of nearly 15 mg per g glucose.
      CONCLUSION: A cytosolic isobutanol production pathway was successfully
      established in yeast by re-localization and optimization of mitochondrial valine
      synthesis enzymes together with overexpression of Aro10 decarboxylase and Adh2
      alcohol dehydrogenase. Driving forces were generated by blocking competition with
      the mitochondrial valine pathway and by omitting valine from the fermentation
      medium. Additional deletion of pyruvate decarboxylase genes and engineering of co
      factor imbalances should lead to even higher isobutanol production.

PMID- 22954228
TI  - Efficient and scalable enantioselective synthesis of a CGRP antagonist.
AB  - An enantioselective synthesis of the CGRP antagonist BMS-846372, amenable to
      large scale preparation, is presented. This new synthesis showcases a chemo- and
      enantioselective reduction of a cyclohepta[b]pyridine-5,9-dione as well as a Pd
      catalyzed alpha-arylation reaction to form the key carbon-carbon bond and set the
      absolute and relative stereochemistry.

PMID- 22954229
TI  - Gauging food and nutritional care quality in hospitals.
AB  - BACKGROUND: Food and nutritional care quality must be assessed and scored, so as
      to improve health institution efficacy. This study aimed to detect and compare
      actions related to food and nutritional care quality in public and private
      hospitals. METHODS: Investigation of the Hospital Food and Nutrition Service
      (HFNS) of 37 hospitals by means of structured interviews assessing two quality
      control corpora, namely nutritional care quality (NCQ) and hospital food service
      quality (FSQ). HFNS was also evaluated with respect to human resources per
      hospital bed and per produced meal. RESULTS: Comparison between public and
      private institutions revealed that there was a statistically significant
      difference between the number of hospital beds per HFNS staff member (p = 0.02)
      and per dietitian (p < 0.01). The mean compliance with NCQ criteria in public and
      private institutions was 51.8% and 41.6%, respectively. The percentage of public
      and private health institutions in conformity with FSQ criteria was 42.4% and
      49.1%, respectively. Most of the actions comprising each corpus, NCQ and FSQ,
      varied considerably between the two types of institution. NCQ was positively
      influenced by hospital type (general) and presence of a clinical dietitian. FSQ
      was affected by institution size: large and medium-sized hospitals were
      significantly better than small ones. CONCLUSIONS: Food and nutritional care in
      hospital is still incipient, and actions concerning both nutritional care and
      food service take place on an irregular basis. It is clear that the design of
      food and nutritional care in hospital indicators is mandatory, and that
      guidelines for the development of actions as well as qualification and assessment
      of nutritional care are urgent.

PMID- 22954230
TI  - Microbubble formation from plasma polymers.
AB  - We document the formation of liquid-like particles in a toluene glow discharge
      that subsequently solidify via a process that releases hydrogen to form a solid
      microbubble with micrometer-size diameter, nanometer-size shell thickness, and
      high volume fraction, in excess of 90%. Liquid-like particles are produced in a
      toluene plasma under conditions that promote low degree of cross-linking (low
      power, high pressure). When these are transferred for observation in TEM, they
      are seen to transform under irradiation by the electron beam into solid bubbles
      with diameter of about 3 MUm. This transformation also takes place under laser
      irradiation of sufficient power and under heating. We present evidence that the
      formation of these microbubbles is due to solidification of the liquid-like
      precursor that is accompanied by release of hydrogen. This mechanism is supported
      by a geometric model that provides a quantitative description of the particle
      size before and after solidification. These unique stimuli-responsive particles
      exhibit the potential of using temperature, electron beam, or laser as a source
      to change their size and structure which may find application in thermal
      insulators, lightweight materials, and light scattering agents.

PMID- 22954231
TI  - Division of labor in colonies of the eusocial wasp, Mischocyttarus consimilis.
AB  - The division of labor between castes and the division of labor in workers
      according to age (temporal polyethism) in social wasps are crucial for
      maintaining social organization. This study evaluated the division of labor
      between castes, and the temporal polyethism in workers of Mischocyttarus
      consimilis Zikan (Hymenoptera: Vespidae). To describe the behavioral repertory of
      this species, observations were made of 21 colonies, with 100 hours of
      observations. In order to observe temporal polyethism, each newly emerged wasp
      was marked with colored dots on the upper area of the thorax. This allowed the
      observation of behavioral acts performed by each worker from the time of
      emergence to its death. Through hybrid multidimensional scaling, a clear division
      between queens and workers could be identified, in which the behaviors of
      physical dominance and food solicitation characterized the queen caste; while
      behaviors such as adult-adult trophallaxis, destruction of cells, alarm, foraging
      for prey, foraging for nectar, and unsuccessful foraging characterized the worker
      caste. Hybrid multidimensional scaling characterized two groups, with intra-nest
      activities preferentially accomplished by younger workers, while extra-nest
      activities such as foraging were executed more frequently by older workers.

PMID- 22954232
TI  - Supplementation of culture medium with L-carnitine improves development and
      cryotolerance of bovine embryos produced in vitro.
AB  - High lipid content in embryos is associated with low freezing tolerance. This
      study assessed the effects of exogenous L-carnitine, an enhancer of lipid
      metabolism, on the in vitro development and freezing survival of bovine embryos.
      Also, effects on metabolic activity, reactive oxygen species (ROS) and apoptosis
      were investigated. Supplementation of embryo culture medium with 1.518 mM or
      3.030 mM L-carnitine significantly increased the rates of zygote development to
      the blastocyst stage and blastocyst cell numbers whereas 6.072 mM of this
      compound did not improve embryo development. Survival rates after slow freezing
      of blastocysts were significantly higher when embryos were cultured in the
      presence of 1.518 mM or 3.030 mM L-carnitine compared with the control. A lower
      density of lipid droplets was detected in L-carnitine-treated blastocysts
      compared with the control. L-carnitine significantly reduced ROS levels in 2-cell
      embryos but did not reduce ROS levels at later stages. The apoptotic cell rate
      was not different between control and L-carnitine-treated blastocysts. L
      carnitine significantly increased ATP levels in 2-cell embryos but not at the 8
      cell or blastocyst stages. L-carnitine increased the expression of metabolism
      related ATP6 and COX1 genes in blastocysts. In conclusion, L-carnitine
      supplementation enhanced lipid metabolism in embryos resulting in improved
      development and cryotolerance of bovine blastocysts produced in vitro.

PMID- 22954233
TI  - Association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine
      and the cardiac function in hypertensive patients without overt heart disease.
AB  - Although increased oxidative stress is known to be associated with worsened
      cardiac function in chronic heart failure, consensus is still lacking regarding
      the association between oxidative stress and cardiac function in hypertensive
      patients without overt heart disease. This study aimed to evaluate the
      association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine
      (8-OHdG) and cardiac function in hypertensive patients without overt heart
      disease. We enrolled a total of 80 hypertensive patients (70 +/- 11 y) who had
      been taking antihypertensive medications for at least 1 year. Urinary 8-OHdG
      levels were measured by an immunochromatographic assay (ICR-001, Selista Inc.,
      Tokyo, Japan). Echocardiography was performed to assess the left ventricular (LV)
      diastolic function by measuring early diastolic mitral annular velocity (e') and
      the ratio of early transmitral flow velocity (E) to e' (E/e'). Urinary 8-OHdG was
      correlated with E/e' (r = 0.346, P = .002), e' (r = -0.310, P = .005), and HbA1c
      (r = 0.276, P = .013). Multiple linear regression analysis revealed that only e'
      (beta = -0.343, P = .004) was an independent determinant of urinary 8-OHdG. In
      conclusion, decreased e' is independently associated with elevated urinary 8
      OHdG, a marker of oxidative stress, in hypertensive patients. Therefore, an
      elevated urinary 8-OHdG level may be useful in detecting subclinical LV diastolic
      dysfunction in hypertensive patients without overt heart disease. 

PMID- 22954234
TI  - Real polymer-free sirolimus- and probucol-eluting versus biodegradable polymer
      sirolimus-eluting stents for obstructive coronary artery disease: DKPLUS-Wave 1,
      a multicenter, randomized, prospective trial.
AB  - BACKGROUND: Polymer-free sirolimus- and probucol-eluting stents (Real Dual drug
      eluting stents [DES]) is as effective as first-generation DES in treating
      coronary artery stenosis. It is unknown whether sirolimus-eluting stents
      containing biodegradable polymer (Excel) would be superior to real Dual DES. This
      study aimed to investigate the difference in target vessel revascularization
      (TVR) at 12 months in patients with coronary artery disease treated by the
      implantation of Dual DES or Excel stents. METHODS: Three hundred and forty-six
      patients with de novo coronary artery disease were recruited from six centers in
      China and randomly assigned to either the Dual DES or the Excel group. The
      primary endpoint was the occurrence of TVR at 12 months. The secondary endpoint
      was angiographic in-stent restenosis and late lumen loss at 13 months. Stent
      thrombosis (ST) served as the safety endpoint. Dual anti-platelet therapy (DAPT)
      was prescribed for 6 months. RESULTS: Clinical follow-up for 12 months and repeat
      angiography at 13 months were available in 100% and >90% of patients,
      respectively. The ISR and in-stent late loss were significantly different between
      the Excel (3.1%, 0.09 +/- 0.11 mm) and the Dual DES (19.5%, 0.36 +/- 0.32 mm, P <
      0.001, P < 0.001, respectively) groups. The TVR (3.5%) in the Excel group was
      significantly less than in the Dual DES group (13.9%, P = 0.001). The ST rate
      beyond 12 months in the Dual DES group was 0%, and this was 1.2% in the Excel
      group (P = 0.499). CONCLUSIONS: The Excel stent was statistically superior to the
      Dual DES in terms of restenosis, late loss, and TVR for long lesions.

PMID- 22954235
TI  - The complete mitochondrial genome of Percocypris pingi (Teleostei,
      Cypriniformes).
AB  - Percocypris pingi is an endemic and economic fish species only found in the upper
      Yangtze River basin in China. It has become endangered in recent years due to
      overfishing and/or dam construction. However, the available genetic data are
      still scarce for this species. Here, we sequenced the complete mitochondrial
      genome sequence of P. pingi using long polymerase chain reactions. The complete
      mitogenome sequence has 16,586 bp and contains the usual 13 protein-coding genes,
      2 ribosomal RNA genes, 22 transfer RNA (tRNA) genes, and 1 control region, the
      gene composition and order of which are similar to most of other vertebrates.
      Most mitochondrial genes except ND6 and eight tRNAs are encoded on the heavy
      strand. The overall base composition of the heavy strand is 30.9% A, 25.7% T,
      26.6% C, and 16.8% G with a slight AT bias of 56.6%. There are seven regions of
      gene overlaps totaling 23 bp and 11 intergenic spacer regions totaling 35 bp.
      Combined with the COI barcoding region sequences of other 25 cyprinids, the
      phylogenetic position of P. pingi was estimated using neighbor-joining method.
      The results showed that P. pingi had a close phylogenetic relationship with the
      species from genus Schizothorax. This mitogenome sequence data of P. pingi would
      provide the fundamental genetic data for further conservation genetic studies for
      this endangered fish species.

PMID- 22954236
TI  - Ghrelin and obestatin expression in serous ovarian tumours.
AB  - OBJECTIVE: To investigate ghrelin and obestatin expression in serous ovarian
      tumours. MATERIALS AND METHODS: Preparations of deparaffinized blocks obtained
      from the pathology archives of a total of 47 previously diagnosed cases of benign
      serous tumour (n = 20), borderline serous tumour (n = 7) and malignant serous
      tumour (n = 20) were subjected to immunohistochemical examination to find out
      ghrelin and obestatin expressions. RESULTS: Mean ghrelin expressions decreased
      significantly in the benign group, relative to the malignant group (p < 0.05),
      while there was no significant change in mean obestatin expression. It was
      established that rates of preparations with moderate and severe ghrelin and
      obestatin expression displayed a significant increase from benign to malignant
      ones (p < 0.05). CONCLUSION: The fact that rates of preparations with severe
      expression correlated with an increase in malignancy suggests that ghrelin and
      obestatin may be effective in the malignant transformation in at least some
      cases.

PMID- 22954237
TI  - Synthesis of substituted phenanthrene by iron(III)-catalyzed intramolecular
      alkyne-carbonyl metathesis.
AB  - An efficient synthesis of functionalized phenanthrenes has been developed for the
      first time involving an iron(III)-catalyzed intramolecular coupling of 2'-alkynyl
      biphenyl-2-carbaldehydes. A broad range of functionalized phenanthrene
      derivatives could be obtained in the present method in moderate to good yields
      with high chemo- and regioselectivity. This transformation can also be applied to
      the synthesis of an angularly fused tetracyclic compound. This method offers
      several advantages such as high selectivity, mild reaction conditions, and easy
      availability of starting materials.

PMID- 22954238
TI  - Supervised chemical pattern recognition in almond ( Prunus dulcis ) Portuguese
      PDO cultivars: PCA- and LDA-based triennial study.
AB  - Almonds harvested in three years in Tras-os-Montes (Portugal) were characterized
      to find differences among Protected Designation of Origin (PDO) Amendoa Douro and
      commercial non-PDO cultivars. Nutritional parameters, fiber (neutral and acid
      detergent fibers, acid detergent lignin, and cellulose), fatty acids,
      triacylglycerols (TAG), and tocopherols were evaluated. Fat was the major
      component, followed by carbohydrates, protein, and moisture. Fatty acids were
      mostly detected as monounsaturated and polyunsaturated forms, with relevance of
      oleic and linoleic acids. Accordingly, 1,2,3-trioleoylglycerol and 1,2-dioleoyl-3
      linoleoylglycerol were the major TAG. alpha-Tocopherol was the leading
      tocopherol. To verify statistical differences among PDO and non-PDO cultivars
      independent of the harvest year, data were analyzed through an analysis of
      variance, a principal component analysis, and a linear discriminant analysis
      (LDA). These differences identified classification parameters, providing an
      important tool for authenticity purposes. The best results were achieved with TAG
      analysis coupled with LDA, which proved its effectiveness to discriminate almond
      cultivars.

PMID- 22954239
TI  - Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!
AB  - In the current pathophysiological model of chronic ischemic heart disease (IHD),
      myocardial ischemia and exertional angina are caused by obstructive
      atherosclerotic plaque, and the clinical management of IHD is centered on the
      identification and removal of the stenosis. Although this approach has been in
      place for years, several lines of evidence, including poor prognostic impact,
      suggest that this direct relationship may present an oversimplified view of IHD.
      Indeed, a large number of studies have found that IHD can occur in the presence
      or absence of obstructive coronary artery disease and that atherosclerosis is
      just 1 element in a complex multifactorial pathophysiological process that
      includes inflammation, microvascular coronary dysfunction, endothelial
      dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates
      underscore the fact that removing stenosis in patients with stable IHD does not
      address the underlying pathological mechanisms that lead to the progression of
      nonculprit lesions. The model proposed herein shifts the focus away from
      obstructive epicardial coronary atherosclerosis and centers it on the
      microvasculature and myocardial cell where the ischemia is taking place. If the
      myocardial cell is placed at the center of the model, all the potential
      pathological inputs can be considered, and strategies that protect the
      cardiomyocytes from ischemic damage, regardless of the causative mechanism, can
      be developed.

PMID- 22954240
TI  - Rethinking stable ischemic heart disease: is this the beginning of a new era?

PMID- 22954241
TI  - Unmasking a giant ventricular pseudoaneurysm.

PMID- 22954242
TI  - Challenging interpretation of elevated cardiac troponin T in a complex case with
      rhabdomyolysis.

PMID- 22954244
TI  - Osteoporosis is a major confounder in observational studies investigating
      bisphosphonate therapy in aortic stenosis.

PMID- 22954246
TI  - Multidetector computed tomography for detecting lesions that are at high risk for
      myocardial necrosis after percutaneous coronary intervention.

PMID- 22954248
TI  - "Smoking" mitral valve.

PMID- 22954249
TI  - Dioxin-like potency of HO- and MeO- analogues of PBDEs' the potential risk
      through consumption of fish from eastern China.
AB  - Polybrominated diphenyl ethers (PBDEs) and their analogues, such as hydroxylated
      PBDE (HO-PBDEs) and methoxylated PBDE (MeO-PBDEs) are of interest due to their
      wide distribution, bioaccumulation and potential toxicity to humans and wildlife.
      While information on the toxicity/biological potencies of PBDEs was available,
      information on analogues of PBDEs was limited. Dioxin-like toxicity of 34 PBDEs
      analogues was evaluated by use of the H4IIE-luc, rat hepatoma transactivation
      bioassay in 384-well plate format at concentrations ranging from 0 to 10 000
      ng/mL. Among the 34 target analogues of PBDEs studied here, 19 activated the aryl
      hydrocarbon receptor (AhR) and induced significant dioxin-like responses in H4IIE
      luc cells. Efficacies of the analogues of PBDEs ranged from 5.0% to 101.8% of the
      maximum response caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-max) and
      their respective 2,3,7,8-TCDD potency factors (ReP(H4IIE-luc)) ranged from 7.35 *
      10(-12) to 4.00 * 10(-4), some of which were equal to or more potent than some
      mono-ortho-substituted PCBs (TEF-(WHO) = 3 * 10(-5)). HO-PBDEs exhibited greater
      dioxin-like activity than did the corresponding MeO-PBDEs. Analogues of PBDEs
      were detected mostly in marine organisms. Of these 11 detected analogues of
      PBDEs, 6 were found to have measurable dioxin-like potency. Though some analogues
      of PBDEs exhibited significant dioxin-like potency as measured by responses of
      the H4IIE-luc transactivation assay, concentrations of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) equivalents ((PBDEs analogues)TEQ(H4IIE-luc)), calculated as the
      sum of the product of concentrations of individual PBDE and their ReP(H4IIE-luc),
      were less than the tolerance limit proposed by European Union and the oral
      reference dose (RfD) derived by U.S. Environmental Protection Agency,
      respectively. (Hazard Quotients (HQ) < 0.005) Additional investigations should be
      conducted to evaluate the toxic potencies of these chemicals, especially for 2'
      MeO-BDE-28, 4-HO-BDE-90, 6-HO-BDE-47, and 6-MeO-BDE-47, which had been detected
      in other environmental media, including human blood.

PMID- 22954250
TI  - Noninvasive imaging of intracellular lipid metabolism in macrophages by Raman
      microscopy in combination with stable isotopic labeling.
AB  - Monocyte-derived macrophages play a key role in atherogenesis because their
      transformation into foam cells is responsible for deposition of lipids in plaques
      within arterial walls. The appearance of cytosolic lipid droplets is a hallmark
      of macrophage foam cell formation, and the molecular basics involved in this
      process are not well understood. Of particular interest is the intracellular fate
      of different individual lipid species, such as fatty acids or cholesterol. Here,
      we utilize Raman microscopy to image the metabolism of such lipids and to trace
      their subsequent storage patterns. The combination of microscopic information
      with Raman spectroscopy provides a powerful molecular imaging method, which
      allows visualization at the diffraction limit of the employed laser light and
      biochemical characterization through associated spectral information. In order to
      distinguish the molecules of interest from other naturally occurring lipids
      spectroscopically, deuterium labels were introduced. Intracellular distribution
      and metabolic changes were observed for serum albumin-complexed palmitic and
      oleic acid and cholesterol and quantitatively evaluated by monitoring the
      increase in CD scattering intensities at 0.5, 1, 3, 6, 24, 30, and 36 h. This
      approach may also allow for investigating the cellular trafficking of other
      molecules, such as nutrients, metabolites, and drugs.

PMID- 22954251
TI  - Advances in drug design with RXR modulators.
AB  - INTRODUCTION: Retinoid X receptors (subtypes RXRalpha or NR2B1, RXRbeta or NR2B2
      and RXRgamma or NR2B3, which originate from three distinct genes) are promiscuous
      partners with heterodimeric associations to other members of the Nuclear Receptor
      (NR) superfamily. Some of the heterodimers are "permissive" and transcriptionally
      active in the presence of either an RXR ligand ("rexinoid") or a NR partner
      ligand, whereas others are "non-permissive" and unresponsive to rexinoids alone.
      In rodent models, rexinoids and partner agonists (mainly PPARgamma, LXR, FXR)
      produce beneficial effects on insulin sensitization, diabetes and obesity, but
      secondary effects have also been noted, such as a raise in tryglyceride levels,
      supression of the thyroid hormone axis and induction of hepatomegaly. AREAS
      COVERED: The authors review recent advances in rexinoid design, including further
      optimization of known scaffolds, and the discovery of novel RXR modulators by
      virtual ligand screening or from bioactive natural products. The understanding of
      rexinoid functions in permissive and non-permissive heterodimers is firmly based
      on structural knowledge. By strenghtening or disrupting the interaction surface
      with coregulators rexinoids exert agonist or (partial) antagonist activities. The
      activity state of the heterodimer can also be fine-tuned by the cellular context
      and the nature of coregulators. EXPERT OPINION: The synthetic chemistry toolbox
      has provided a panel of agonists, partial (ant)agonists and/or heterodimer
      selective rexinoids starting from existing, naturally occurring or
      serendipitously discovered scaffolds. These compounds have an unexplored
      therapeutic potential that might overcome some of the current limitations of
      rexinoids in therapy, such as hypertriglyceridemia.

PMID- 22954252
TI  - Theoretical investigations on the electronic and optical properties of bridged
      oligothiophenes.
AB  - A study of the structure, electronic, and optical properties of oligothiophenes
      is reported. Geometry optimizations of the ground state of derivatives of these
      molecules were carried out using the density functional theory (DFT) with the
      B3LYP functional and the 6-31G(d) basis set. Bridged oligothiophenes by C?O, C?S,
      and C?C(CN)(2) functional groups were found to be planar in their electronic
      ground states (S(0)). The electronic excitation transitions of the bridged
      oligothiophenes were investigated using the time-dependent TD-DFT method
      performed on the ground-state optimized geometries. For all the derivatives,
      excitation to the S(1) state corresponds mainly to the HOMO -> LUMO transition.
      The excitation energies are found in fair agreement with the experimental values.
      The optimization (relaxation) of the first singlet excited electronic state
      (S(1)) has been done using the restricted configuration interaction (singles)
      (RCIS/6-31G(d) approach. The electronically excited geometries favor a more
      quinoidic type structure. Emission energies have been obtained from TD-DFT
      calculations performed on the excited-state optimized geometries S(1). The change
      of group (C?O, C?S, and C?C(CN)(2)) as well as the incorporation of monomer
      moieties induce a significant decrease in the excitation and emission energies.

PMID- 22954253
TI  - Hydrocele on the web: an evaluation of Internet-based information.
AB  - OBJECTIVE: To evaluate the quality of health-based information available to
      patients and their parents on the Internet regarding hydrocele, a common
      paediatric condition, an Internet search was performed and a questionnaire
      distributed. MATERIAL AND METHODS: The top 100 websites from the five most
      accessed search engines were reviewed by entering the term "Hydrocele" into each
      search engine. Website authorship was determined by close examination of each
      website. Websites were assessed for accuracy and validity according to the Health
      On the Net Foundation Code (HONcode), DISCERN score and JAMA benchmark criteria,
      recognized scoring systems. A voluntary written questionnaire was distributed to
      parents of patients on two consecutive days outside a paediatric clinic. RESULTS:
      After duplicate and inaccessible sites had been excluded, 37 unique websites were
      identified: 11 were academic, eight were produced by physicians not affiliated
      with an academic institution, three were commercial, four were attached to
      discussion groups or social media sites, four were media related and seven were
      unspecified. There was a significant difference between the academic and the
      physician-related sites compared with the other categories, with academic and
      physician sites scoring highest on the recognized scoring systems (p = 0.0001).
      It was found that 56.7% of patients accessed the Internet regarding their
      condition and 33% believed this information to be accurate. CONCLUSION: The
      quality of health-related information overall is of a poor quality. Academic and
      physician-provided websites were shown to contain better quality information.
      Clinicians have a potential role not only to direct patients to appropriate
      sites, but also to help to develop content on the Internet.

PMID- 22954254
TI  - Multiple transitions in sick leave, disability benefits, and return to work. - A
      4-year follow-up of patients participating in a work-related rehabilitation
      program.
AB  - BACKGROUND: Return to work (RTW) after long-term sick leave can be a long-lasting
      process where the individual may shift between work and receiving different
      social security benefits, as well as between part-time and full-time work. This
      is a challenge in the assessment of RTW outcomes after rehabilitation
      interventions. The aim of this study was to analyse the probability for RTW, and
      the probabilities of transitions between different benefits during a 4-year
      follow-up, after participating in a work-related rehabilitation program. METHODS:
      The sample consisted of 584 patients (66% females), mean age 44 years (sd = 9.3).
      Mean duration on various types of sick leave benefits at entry to the
      rehabilitation program was 9.3 months (sd = 3.4)]. The patients had mental (47%),
      musculoskeletal (46%), or other diagnoses (7%). Official national register data
      over a 4-year follow-up period was analysed. Extended statistical tools for
      multistate models were used to calculate transition probabilities between the
      following eight states; working, partial sick leave, full-time sick leave,
      medical rehabilitation, vocational rehabilitation, and disability pension;
      (partial, permanent and time-limited). RESULTS: During the follow-up there was an
      increased probability for working, a decreased probability for being on sick
      leave, and an increased probability for being on disability pension. The
      probability of RTW was not related to the work and benefit status at departure
      from the rehabilitation clinic. The patients had an average of 3.7 (range 0-18)
      transitions between work and the different benefits. CONCLUSIONS: The process of
      RTW or of receiving disability pension was complex, and may take several years,
      with multiple transitions between work and different benefits. Access to reliable
      register data and the use of a multistate RTW model, makes it possible to
      describe the developmental nature and the different levels of the recovery and
      disability process.

PMID- 22954255
TI  - A possible primary cause of cancer: deficient cellular interactions in endocrine
      pancreas.
AB  - BACKGROUND: Cancer is a devastating type of disease. New and innovative ways to
      tackle cancers that have so far proved refractive to conventional therapies is
      urgently needed. It is becoming increasingly clear that, in addition to
      conventional therapeutics targeting by small molecules, that tumor cell
      metabolism presents new opportunities to target selectively specific cancer cell
      populations. Metabolic defects in cancer cells can be manifested in many ways
      that might not be readily apparent, such as altering epigenetic gene regulation
      for example. The complex rewiring of metabolic pathways gives tumor cells a
      special advantage over differentiated cells, since they deplete body stores as
      fuel for their growth and proliferation. Tumor metabolism looks simpler when we
      consider that some enzymatic switches are in a neoglucogenic direction thereby
      depleting body stores. However, these pathways may be inadequately switched on by
      catabolic hormones (glucagon, epinephrine and cortisol) in a specific situation
      where anabolism is activated by, for example insulin released from beta
      pancreatic cells or IGF, inducing mitosis and synthesis that are powered by
      glucose catabolism. Such a hybrid metabolic situation would be reached if a
      pancreatic beta cell mechanism, mediated by GABA, failed to silence neighboring
      alpha cells and delta cells. The inhibitory transmitter GABA hyperpolarizes alpha
      and delta cells via their GABA A receptors, and blocks the release of glucagon
      and somatostatin. Alternatively, an anomaly of alpha cell channels, would lead to
      a similar situation. Whatever is the alteration, anabolism fails to silence
      catabolism and enzymatic switches controlled by kinases and phosphatases adopt an
      inadequate direction, leading to a hybrid metabolic rewiring found in cancer. It
      is daring to formulate such a hypothesis as this. However, it is quite possible
      that the starting point in cancer is an alteration of the endocrine pancreas,
      suppressing the mechanism by which beta cells silence the neighboring alpha and
      delta cells, with GABA and Zn2+.

PMID- 22954257
TI  - Computational study of anomalous reduction potentials for hydrogen evolution
      catalyzed by cobalt dithiolene complexes.
AB  - The design of efficient hydrogen-evolving catalysts based on earth-abundant
      materials is important for developing alternative renewable energy sources. A
      series of four hydrogen-evolving cobalt dithiolene complexes in acetonitrile
      water solvent is studied with computational methods. Co(mnt)(2) (mnt =
      maleonitrile-2,3-dithiolate) has been shown experimentally to be the least active
      electrocatalyst (i.e., to produce H(2) at the most negative potential) in this
      series, even though it has the most strongly electron-withdrawing substituents
      and the least negative Co(III/II) reduction potential. The calculations provide
      an explanation for this anomalous behavior in terms of protonation of the sulfur
      atoms on the dithiolene ligands after the initial Co(III/II) reduction. One fewer
      sulfur atom is protonated in the Co(II)(mnt)(2) complex than in the other three
      complexes in the series. As a result, the subsequent Co(II/I) reduction step
      occurs at the most negative potential for Co(mnt)(2). According to the proposed
      mechanism, the resulting Co(I) complex undergoes intramolecular proton transfer
      to form a catalytically active Co(III)-hydride that can further react to produce
      H(2). Understanding the impact of ligand protonation on electrocatalytic activity
      is important for designing more effective electrocatalysts for solar devices.

PMID- 22954256
TI  - Human breast cancer associated fibroblasts exhibit subtype specific gene
      expression profiles.
AB  - BACKGROUND: Breast cancer is a heterogeneous disease for which prognosis and
      treatment strategies are largely governed by the receptor status (estrogen,
      progesterone and Her2) of the tumor cells. Gene expression profiling of whole
      breast tumors further stratifies breast cancer into several molecular subtypes
      which also co-segregate with the receptor status of the tumor cells. We
      postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may
      exhibit subtype specific gene expression profiles and thus contribute to the
      biology of the disease in a subtype specific manner. Several studies have
      reported gene expression profile differences between CAFs and normal breast
      fibroblasts but in none of these studies were the results stratified based on
      tumor subtypes. METHODS: To address whether gene expression in breast cancer
      associated fibroblasts varies between breast cancer subtypes, we compared the
      gene expression profiles of early passage primary CAFs isolated from twenty human
      breast cancer samples representing three main subtypes; seven ER+, seven triple
      negative (TNBC) and six Her2+. RESULTS: We observed significant expression
      differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and
      ER + cancers, particularly in pathways associated with cytoskeleton and integrin
      signaling. In the case of Her2+ breast cancer, the signaling pathways found to be
      selectively up regulated in CAFs likely contribute to the enhanced migration of
      breast cancer cells in transwell assays and may contribute to the unfavorable
      prognosis of Her2+ breast cancer. CONCLUSIONS: These data demonstrate that in
      addition to the distinct molecular profiles that characterize the neoplastic
      cells, CAF gene expression is also differentially regulated in distinct subtypes
      of breast cancer.

PMID- 22954258
TI  - Optical properties of responsive hybrid au@polymer nanoparticles.
AB  - This work presents a novel modeling approach to calculate the optical properties
      of gold nanoparticles coated with stimuli-responsive polymers. This approach
      combines, for the first time, a molecular description of the soft material with
      an electrodynamics calculation of the optical properties of the system. A mean
      field molecular theory is first used to calculate the local density of the
      polymer and the position-dependent dielectric constant surrounding the
      nanoparticle. This information is then used to calculate the optical properties
      of the Au@polymer colloid by solving Maxwell's equations for an incident
      electromagnetic wave. Motivated by the interest in Au@PNIPAM and Au@PVP
      experimental systems, the theory is applied to study the effect of polymer
      collapse on the position of the localized surface plasmon resonance (LSPR) of the
      system. The most important results of the present study are as follows: (i) the
      LSPR always shifts to lower energies upon polymer collapse (in agreement with
      experimental results); this observation implies that the red shift expected due
      to increasing polymer density always overcomes the blue shift expected from
      decreasing layer thickness; (ii) the magnitude of the LSPR shift depends
      nonmonotonically on surface coverage and nanoparticle radius; and (iii) the
      formation of aggregates on the nanoparticle surface (due to microphase
      segregation) decreases the magnitude of the LSPR shift. These results highlight
      the importance of explicitly considering the coupling between the soft material
      and the inorganic components in determining the optical properties of the hybrid
      system.

PMID- 22954259
TI  - Regionally specific alterations in functional connectivity of the anterior
      cingulate cortex in major depressive disorder.
AB  - BACKGROUND: Depression has been associated with functional alterations in several
      areas of the cingulate cortex. In this study we have taken a systematic approach
      to examining how alterations in functional connectivity vary across the
      functionally diverse subregions of the rostral cingulate cortex. Method Eighteen
      patients with major depressive disorder, aged 15 to 24 years, were matched with
      20 healthy control participants. Using resting-state functional connectivity
      magnetic resonance imaging (fcMRI), we systematically investigated the functional
      connectivity of four subregions of the rostral cingulate cortex. Voxelwise
      statistical maps of each subregion's connectivity with other brain areas were
      compared between the patient and control groups. RESULTS: The depressed
      participants showed altered patterns of connectivity with ventral cingulate
      subregions. They showed increased connectivity between subgenual anterior
      cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength
      showing positive correlation with illness severity. Depressed participants also
      showed increased connectivity between pregenual ACC and left dorsolateral frontal
      cortex, and decreased connectivity between pregenual ACC and the caudate nucleus
      bilaterally. CONCLUSIONS: The results reinforce the importance of subgenual ACC
      for depression, and show a close link between brain regions that support self
      related processes and affective visceromotor function. The pregenual ACC also has
      an important role, with its increased connectivity with dorsolateral frontal
      cortex suggesting heightened cognitive regulation of affect; and reduced
      connectivity with the caudate nucleus potentially underlying symptoms such as
      anhedonia, reduced motivation and psychomotor dysfunction.

PMID- 22954260
TI  - Pretreatment of Asian elephant (Elephas maximus) spermatozoa with cholesterol
      loaded cyclodextrins and glycerol addition at 4 degrees C improves cryosurvival.
AB  - Asian elephant spermatozoa are sensitive to chilling and do not respond well to
      cryopreservation. The objectives of the present study were to: (1) determine
      whether cholesterol content can be modified by preincubation of Asian elephant
      spermatozoa with cholesterol-loaded cyclodextrin (CLC); and (2) assess the
      effects of CLC concentration(s), temperature at time of glycerol addition (22
      degrees C vs 4 degrees C) and dilution medium on post-thaw sperm survival.
      Spermatozoa incubated with >=1.5 mg CLC exhibited increased (P < 0.05)
      cholesterol concentrations. Pretreatment of spermatozoa with 1.5 mg CLC resulted
      in improvements (P < 0.05) in all post-thaw parameters. Glycerol addition at 4
      degrees C also improved all post-thaw parameters compared with 22 degrees C.
      Dilution of thawed spermatozoa in an egg yolk-based medium improved (P < 0.05)
      motility compared with Ham's F-10 culture medium. In summary, our findings
      indicate that modifying cholesterol content within the plasma membrane improves
      the cryosurvival of Asian elephant spermatozoa. The development of an improved
      cryopreservation method that includes modification of membrane cholesterol and
      the addition of glycerol at 4 degrees C, as reported in the present study, is an
      important step towards utilisation of cryopreserved spermatozoa in captive
      management of this species.

PMID- 22954261
TI  - Delivery room respiratory management of the term and preterm infant.
AB  - The immediate newborn transition is a time of great physiologic adjustments and
      many infants need assistance to make a successful transition to newborn life.
      Assisted ventilation is the most important intervention performed during this
      transitional period. Noninvasive ventilation is a necessary skill for all
      pediatric providers because it is the most frequently required lifesaving measure
      provided in the delivery room. Providing ventilation in the least injurious
      manner is also necessary and many aspects of how this can best be done are still
      unknown. Following the normal physiology of fetal to neonatal transition
      continues to be a logical, but challenging, approach to initial ventilatory
      support of the newborn in the delivery room.

PMID- 22954263
TI  - Initial respiratory support of preterm infants: the role of CPAP, the INSURE
      method, and noninvasive ventilation.
AB  - This article explores the potential benefits and risks for the various approaches
      to the initial respiratory management of preterm infants. The authors focus on
      the evidence for the increasingly used strategies of initial respiratory support
      of preterm infants with continuous positive airway pressure (CPAP) beginning in
      the delivery room or very early in the hospital course and blended strategies
      involving the early administration of surfactant replacement followed by
      immediate extubation and stabilization on CPAP. Where possible, the evidence
      referenced in this review comes from individual randomized controlled trials or
      meta-analyses of those trials.

PMID- 22954262
TI  - Effects of chorioamnionitis on the fetal lung.
AB  - Very preterm infants are commonly exposed to a chronic, often asymptomatic,
      chorioamnionitis that is diagnosed by histologic evaluation of the placenta only
      after delivery. The reported effects of these exposures on fetal lungs are
      inconsistent because exposure to different organisms, durations of exposure, and
      fetal/maternal responses affect outcomes. In experimental models,
      chorioamnionitis can both injure and mature the fetal lung and cause immune
      nodulation. Postnatal care strategies also change how chorioamnionitis relates to
      clinical outcomes such as bronchopulmonary dysplasia.

PMID- 22954264
TI  - Which continuous positive airway pressure system is best for the preterm infant
      with respiratory distress syndrome?
AB  - Various commercial and home-made continuous positive airway pressure (CPAP)
      systems are described in this article. CPAP may be delivered via a range of
      device-patient interfaces; nasal CPAP is most common, and short binasal prongs
      impose the least extrinsic load impedance on the infant. The source of pressure
      generation is categorized as either constant pressure or constant flow. The
      efficacy of different systems may vary according to whether lung volume
      recruitment, airway patency, minimization of work of breathing, or central
      nervous system stimulation are the primary goal of the clinical decision to use
      CPAP therapy.

PMID- 22954265
TI  - Noninvasive respiratory support in the preterm infant.
AB  - Multiple randomized controlled trials have suggested that nasal intermittent
      positive pressure ventilation, compared with nasal continuous airway pressure,
      prevents extubation failure and may decrease bronchopulmonary dysplasia. This
      article summarizes these studies and suggests strategies for the use of nasal
      intermittent positive pressure ventilation in neonates.

PMID- 22954266
TI  - Volume-limited and volume-targeted ventilation.
AB  - This article shows that volume-targeted ventilation is physiologically more
      logical than pressure-limited ventilation, and is associated with a reduced risk
      of pneumothorax, hypocarbia, duration of ventilation, death or bronchopulmonary
      dysplasia, and severe intraventricular hemorrhage. Therefore, it should now be
      adopted as the main mode for mechanical ventilation of preterm neonates.

PMID- 22954267
TI  - Synchronized mechanical ventilation using electrical activity of the diaphragm in
      neonates.
AB  - The electrical activity of the diaphragm (Edi) is measured by a specialized
      nasogastric/orogastric tube positioned in the esophagus at the level of the
      crural diaphragm. Neurally adjusted ventilatory assist (NAVA) uses the Edi signal
      as a neural trigger and intrabreath controller to synchronize mechanical
      ventilatory breaths with the patient's respiratory drive and to proportionally
      support the patient's respiratory efforts on a breath-by-breath basis. NAVA
      improves patient-ventilator interaction and synchrony even in the presence of
      large air leaks, and might therefore be an optimal option for noninvasive
      ventilation in neonates.

PMID- 22954268
TI  - Weaning infants from mechanical ventilation.
AB  - Protracted mechanical ventilation is associated with increased morbidity and
      mortality in preterm infants and thus the earliest possible weaning from
      mechanical ventilation is desirable. Weaning protocols may be helpful in
      achieving more rapid reduction in support. There is no clear consensus regarding
      the level of support at which an infant is ready for extubation. An improved
      ability to predict when a preterm infant has a high likelihood of successful
      extubation is highly desirable. In this article, available evidence is reviewed
      and reasonable evidence-based recommendations for expeditious weaning and
      extubation are provided.

PMID- 22954269
TI  - Control of oxygenation during mechanical ventilation in the premature infant.
AB  - Maintenance of oxygen saturation targets is a demanding and tedious task because
      of the frequency with which oxygenation changes, especially in small infants
      receiving prolonged respiratory support. It is clear that the achievement of
      oxygenation targets can be improved by a higher nurse-to-patient ratio and by
      intense staff training. Automated control systems can also improve target
      maintenance, and this is achieved mainly by reducing exposure to hyperoxemia. The
      long-term benefits and safety of this strategy are yet to be determined in
      clinical trials.

PMID- 22954270
TI  - Noninvasive monitoring by photoplethysmography.
AB  - The photoplethysmogram (PPG) is a noninvasive circulatory signal related to the
      pulsatile volume in tissue and is displayed by many pulse oximeters. The PPG is
      similar in appearance to the invasive arterial waveform, but is noninvasive and
      ubiquitous in hospitals. There is increasing interest in seeking circulatory
      information from the PPG and developing techniques for a wide variety of novel
      applications. This article addresses the basic physics of photoplethysmography,
      physiologic principles behind pulse oximetry operation, and recent technological
      advances in the usefulness of the PPG waveform to assess microcirculation and
      intravascular fluid volume monitoring during intensive care.

PMID- 22954272
TI  - Clinical effectiveness and safety of permissive hypercapnia.
AB  - Experimental and clinical data indicate that ventilator strategies with
      permissive hypercapnia may reduce lung injury by a variety of mechanisms. Seven
      randomized controlled trials in preterm neonates suggest that permissive
      hypercapnia started early, before the initiation of mechanical ventilation (in
      conjunction with continuous positive airway pressure), followed by prolonged
      permissive hypercapnia if mechanical ventilation is needed is an alternative to
      early ventilation and surfactant. Permissive hypercapnia may improve pulmonary
      outcomes and survival.

PMID- 22954271
TI  - Predictors of bronchopulmonary dysplasia.
AB  - Although significant advances in respiratory care have been made in neonatal
      medicine, bronchopulmonary dysplasia (BPD) remains the most common serious
      pulmonary morbidity in premature infants. The development of BPD is the result of
      the complex interactions between multiple perinatal and postnatal factors. Early
      identification of infants at the most risk of developing BPD through the use of
      estimators and models may allow a targeted approach at reducing BPD in the
      future.

PMID- 22954274
TI  - Pathophysiology of aerodigestive pulmonary disorders in the neonate.
AB  - No test can provide a definitive diagnosis of aerodigestive disease. When
      interpreting tests, one should weigh the benefits and weaknesses of different
      technologies and methods, scientific appropriateness of the testing conditions,
      clinicopathologic correlation, and pharmacologic approaches. Gastroesophageal
      reflux disease (GERD) symptoms and airway symptoms can coexist, and they cannot
      be distinguished without specific testing and direct observations. Important
      aerodigestive disorders include dysphagia, GERD, and aggravation of airway injury
      due to malfunctions of swallowing or airway protection mechanisms. Objective
      evaluation of aerodigestive reflexes and symptom correlation may provide support
      for evidence-based personalized management of feeding and airway protection
      strategies.

PMID- 22954273
TI  - Can nitric oxide-based therapy prevent bronchopulmonary dysplasia?
AB  - A growing understanding of endogenous nitric oxide (NO) biology is helping to
      explain how and when exogenous NO may confer benefit or harm; this knowledge is
      also helping to identify new better-targeted NO-based therapies. In this review,
      results of the bronchopulmonary dysplasia clinical trials that used inhaled NO in
      the preterm population are placed in context, the biologic basis for novel NO
      therapeutics is considered, and possible future directions for NO-focused
      clinical and basic research in developmental lung disease are identified.

PMID- 22954276
TI  - Novel methods for assessment of right heart structure and function in pulmonary
      hypertension.
AB  - Long-term increases in pulmonary vascular resistance and pulmonary arterial
      pressure resulting from structural alterations and abnormal vasoreactivity of the
      pulmonary vasculature may lead to right ventricular (RV) remodeling. Conventional
      methods of assessment of RV structure and function do not provide sensitive
      markers of RV remodeling for prognostic information. Advances in cardiac imaging
      have provided the capability to obtain quantitative information on the RV
      structure and function. This article reviews the clinical conditions that result
      in PH and discusses the novel and emerging methods for the assessment of right
      heart structure and function in PH in infants and children.

PMID- 22954277
TI  - Cell-based strategies to reconstitute lung function in infants with severe
      bronchopulmonary dysplasia.
AB  - Recent advances in our understanding of stem/progenitor cells and their potential
      to repair damaged organs offer the possibility of cell-based treatments for
      neonatal lung injury. This review summarizes basic concepts of stem/progenitor
      cell biology and discusses the recent advances and challenges of cell-based
      therapies for lung diseases, with a particular focus on bronchopulmonary
      dysplasia (BPD), a form of chronic lung disease that primarily affects very
      preterm infants. Despite advances in perinatal care, BPD still remains the most
      common complication of extreme prematurity, and there is no specific treatment.

PMID- 22954275
TI  - The pulmonary circulation in neonatal respiratory failure.
AB  - The pulmonary circulation rapidly adapts at birth to establish lungs as the site
      of gas exchange. Abnormal transition at birth and/or parenchymal lung disease can
      result in neonatal hypoxemic respiratory failure. This article reviews the
      functional changes in pulmonary hemodynamics and structural changes in pulmonary
      vasculature secondary to (1) normal and abnormal transition at birth, and (2)
      diseases associated with neonatal hypoxemic respiratory failure. Various
      management strategies to correct respiratory failure are also discussed.

PMID- 22954279
TI  - Respiratory care of the newborn: what does the future hold?

PMID- 22954278
TI  - Brain injury in chronically ventilated preterm neonates: collateral damage
      related to ventilation strategy.
AB  - Brain injury is a frequent comorbidity in chronically ventilated preterm infants.
      However, the molecular basis of the brain injury remains incompletely understood.
      This article discusses the subtle (diffuse) form of brain injury that has white
      matter and gray matter lesions without germinal matrix hemorrhage
      intraventricular hemorrhage, posthemorrhagic hydrocephalus, or cystic
      periventricular leukomalacia. This article synthesizes data that suggest that
      diffuse lesions to white matter and gray matter are collateral damage related to
      ventilator strategy. Evidence is introduced from the 2 large-animal, physiologic
      models of evolving neonatal chronic lung disease that suggest that an epigenetic
      mechanism may underlie the collateral damage.

PMID- 22954281
TI  - A new duplication in the mitochondrially encoded tRNA proline gene in a patient
      with dilated cardiomyopathy.
AB  - Mitochondria provide an environment conducive to mutations in DNA molecules
      (mtDNA). Analyses of mtDNA have shown mutations potentially leading to many
      cardiovascular traits. Here, we describe a patient with dilated cardiomyopathy
      and new mtDNA duplication. The patient presented symptoms of heart failure New
      York Heart Association functional class III and was diagnosed with non-familial
      dilated cardiomyopathy with important left ventricular systolic dysfunction.
      Sequencing of mtDNA control region was done, and a 15 bp duplication was observed
      between nucleotides 16,018 and 16,032. Part of this duplication is localized
      within the tRNA proline gene (tRNA(Pro)) that has an important role in cell
      protection against oxidative stress and is considered an important regulatory
      factor for cellular reactive oxygen species balance. This duplication could alter
      the stability or secondary structure of tRNA(Pro), affecting mt-protein
      synthesis. In turn, the presence of duplication in tRNA(Pro) could cause some
      oxidative stress imbalance and, so, mitochondrial dysfunction could result in the
      pathogenicity.

PMID- 22954282
TI  - Larval competition reduces body condition in the female seed beetle,
      Callosobruchus maculatus.
AB  - Early body condition may be important for adult behavior and fitness, and is
      impacted by a number of environmental conditions and biotic interactions. Reduced
      fecundity of adult females exposed to larval competition may be caused by reduced
      body condition or shifts in relative body composition, yet these mechanisms have
      not been well researched. Here, body mass, body size, scaled body mass index, and
      two body components (water content and lean dry mass) of adult Callosobruchus
      maculatus (Fabricius) (Coleoptera: Chrysomelidae: Bruchinae) females exposed to
      larval competition or reared alone were examined. Experimental females emerged at
      significantly smaller body mass and body size than control females. Additionally,
      scaled body mass index and water content, but not lean dry mass, were
      significantly reduced in experimental females. To our knowledge, these are the
      first results that demonstrate a potential mechanism for previously documented
      direct effects of competition on fecundity in female bruchine beetles.

PMID- 22954283
TI  - Can first-trimester screening program detect women at high risk for gestational
      diabetes mellitus?
AB  - This study was designed to compare first-trimester maternal serum biochemical
      markers of aneuploidy and fetal nuchal translucency in pregnancies complicated by
      gestational diabetes mellitus and those of a control group. The study included 60
      gestational diabetic and 60 control women who attended the first-trimester
      combined screening program for Down syndrome between 11 and 14 gestational weeks
      with complete follow-up data and delivered in our institution. Maternal serum
      free beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A and
      fetal nuchal translucency were investigated. The combined risks, double test
      risks and age risks were calculated by PRISCA software version 4.0. Comparison of
      the results between the two groups yielded no significant differences in serum
      levels of free beta-human chorionic gonadotropin and fetal nuchal translucency.
      However, women who developed gestational diabetes mellitus had significantly
      lower pregnancy-associated plasma protein-A. And also, the combined risks and
      double test risks calculated by PRISCA software were statistically higher in
      gestational diabetic women than normal pregnant women. These results suggest that
      differences can be seen between diabetic and healthy pregnant women in first
      trimester maternal serum biochemical markers of aneuploidy.

PMID- 22954284
TI  - Antiulcer activity of the chloroform extract of Bauhinia purpurea leaf.
AB  - CONTEXT: Bauhinia purpurea L. (Fabaceae) is a native plant species of many Asian
      countries, including Malaysia and India. In India, the root, stem, bark, and leaf
      of B. purpurea are used to treat various ailments, including ulcers and stomach
      cancer. OBJECTIVE: In an attempt to establish its pharmacological potential, we
      studied the antiulcer activity of lipid-soluble extract of B. purpurea obtained
      via extraction of air-dried leaves using chloroform. MATERIALS AND METHODS: The
      rats were administered the chloroform extract (dose range of 100-1000 mg/kg)
      orally after 24 h fasting. They were subjected to the absolute ethanol- and
      indomethacin-induced gastric ulcer, and pyloric ligation assays after 30 min. The
      acute toxicity study was conducted using a single oral dose of 5000 mg/kg extract
      and the rats were observed for the period of 14 days. omeprazole (30 mg/kg) was
      used as the standard control. RESULTS: At 5000 mg/kg, the extract produced no
      sign of toxicity in rats. The extract exhibited significant (p < 0.05) dose
      dependent antiulcer activity for the ethanol-induced model. The extract also
      significantly (p < 0.05) increased the gastric wall mucus production and pH of
      gastric content, while significantly (p < 0.05) reducing the total volume and
      total acidity of the gastric content in the pylorus ligation assay. DISCUSSION
      AND CONCLUSION: The extract possesses antiulcer, antisecretory and cytoprotective
      activities, which could be attributed to its flavonoid and tannin content. These
      findings provide new information regarding the potential of lipid-soluble
      compounds of B. purpurea for the prevention and treatment of gastric ulcers.

PMID- 22954285
TI  - Synthesis of furan-3-carboxylic and 4-methylene-4,5-dihydrofuran-3-carboxylic
      esters by direct palladium iodide catalyzed oxidative carbonylation of 3-yne-1,2
      diol derivatives.
AB  - A variety of 3-yne-1,2-diol derivatives 1, bearing a primary or secondary
      alcoholic group at C-1, have been efficiently converted into high value added
      furan-3-carboxylic esters 2 in one step by PdI(2)/KI-catalyzed direct oxidative
      carbonylation, carried out in alcoholic media under relatively mild conditions
      (100  degrees C under 40 atm of a 4/1 mixture of CO and air). Carbonylated furans
      2 were obtained in fair to excellent isolated yields (56-93%) through a
      sequential 5-endo-dig heterocyclization-alkoxycarbonylation-dehydration process,
      using only oxygen as the external oxidant. Under similar conditions, 2-methyl-3
      yne-1,2-diols 3, bearing a tertiary alcoholic group, afforded 4-methylene-4,5
      dihydrofuran-3-carboxylates 4 in satisfactory yields (58-70%).

PMID- 22954286
TI  - "Extreme" Ugi reactions with some complex alpha-amino acids.
AB  - The Ti(IV)-catalyzed Ugi condensation of alpha-amino acids with electron-rich
      aromatic aldehydes performs adequately even with  sterically demanding alpha
      amino carboxylate salts. The reaction occurs diastereoselectively, in some cases
      with virtually complete diastereoselectivity. A stereochemical rationale for the
      reaction is proposed.

PMID- 22954288
TI  - Characterization of crude oils at the molecular level by use of laser desorption
      ionization Fourier-transform ion cyclotron resonance mass spectrometry.
AB  - In this study, laser desorption ionization (LDI) coupled to Fourier-transform ion
      cyclotron resonance mass spectrometry (FTICR MS) was applied to study crude oils
      at the molecular level. Molecular ions were the major type of ion detected by (+)
      mode, and deprotonated and radical anions were the major ions observed by (-)
      mode LDI FTICR MS. N(1) and hydrocarbon classes were dominant in the class
      distribution plots obtained by (+) LDI FTICR MS, but other heteroatom classes,
      including O(x) and S(1), were abundant in plots obtained by (-) LDI FTICR MS.
      Detailed analysis of double-bond equivalence (DBE) vs carbon number plots
      revealed that LDI FTICR MS is more sensitive toward polyaromatic compounds than
      mono- or dicyclic-aromatic compounds. However, nonaromatic and aromatic O(2)
      compounds could be detected simultaneously. An abundance of nonaromatic O(2)
      compounds (presumably naphthenic acids) are correlated with total acid numbers,
      but O(2) compounds with condensed structures are not. Overall, this study shows
      that LDI FTICR MS can be successfully used to study crude oils at the molecular
      level.

PMID- 22954287
TI  - DNA methylation inhibitors, 5-azacytidine and zebularine potentiate the
      transdifferentiation of rat bone marrow mesenchymal stem cells into
      cardiomyocytes.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have immense self-renewal capability.
      They can be differentiated into many cell types and therefore hold great
      potential in the field of regenerative medicine. MSCs can be converted into
      beating cardiomyocytes by treating them with DNA-demethylating agents. Some of
      these compounds are nucleoside analogs that are widely used for studying the role
      of DNA methylation in biological processes as well as for the clinical treatment
      of leukemia and other carcinomas. AIMS: To achieve a better therapeutic option
      for cardiovascular regeneration, this study was carried out using MSCs treated
      with two synthetic compounds, zebularine and 5-azacytidine. It can be expected
      that treated MSCs prior to transplantation may increase the likelihood of
      successful regeneration of damaged myocardium. METHODS: The optimized
      concentrations of these compounds were added separately into the culture medium
      and the treated cells were analyzed for the expression of cardiac-specific genes
      by RT-PCR and cardiac-specific proteins by immunocytochemistry and flow
      cytometry. Treated MSCs were cocultured with cardiomyocytes to see the fusion
      capability of these cells. RESULTS: mRNA and protein expressions of GATA4,
      Nkx2.5, and cardiac troponin T were observed in the treated MSCs. Coculture
      studies of MSCs and cardiomyocytes have shown improved fusion with zebularine
      treated MSCs as compared to untreated and 5-azacytidine-treated MSCs. CONCLUSION:
      The study is expected to put forth another valuable aspect of certain compounds,
      that is, induction of transdifferentiation of MSCs into cardiomyocytes. This
      would serve as a tool for modified cellular therapy and may increase the
      probability of better myocardial regeneration.

PMID- 22954289
TI  - Unraveling the mechanisms of carboxyl ester bond hydrolysis catalyzed by a
      vanadate anion.
AB  - The mechanism of p-nitrophenyl acetate (pNPA) hydrolysis promoted by vanadate
      ions was investigated utilizing both density functional theory and ab initio
      methods. In accordance with experiments, suggesting pure hydrolytic ester bond
      cleavage involving a nucleophilic addition in the rate-limiting transition state,
      four possible B(AC)2 (acyl-oxygen bond cleavage) mode reaction pathways were
      modeled. Moreover, two alternative reaction modes were also considered. Geometry
      optimizations were carried out using B3LYP, BP86, and MPWB1K functionals,
      conjugated with a 6-31++G(d,p) basis set and a Stuttgart effective core potential
      (ECP) for the vanadium atom. Single-point calculations were performed utilizing
      M06, B3LYP-D, and BP86-D functionals as well as B2PLYP-D and MP2 methods with a 6
      311++G(2d,2p) basis set (with and without ECP). To address bulk solvation
      effects, the universal solvation model (SMD) and the conductor-like polarizable
      continuum model were applied, using the parameters of water. All levels of theory
      predict the same reaction mechanism, B(AC)2-1, as the lowest-energy pathway on
      the potential energy surface for pNPA hydrolysis catalyzed by the H(2)VO(4)(-)
      ion in aqueous media. The B(AC)2-1 pathway passes through two transition states,
      the first associated with the nucleophilic addition of H(2)VO(4)(-) and the
      second with the release of p-nitrophenoxide ion (pNP(-)), linked with a
      tetrahedral intermediate state. The intermediate structure is stabilized via
      protonation of the acyl oxygen atom by the vanadate and formation of an
      intramolecular hydrogen bond. The first and second barrier heights are 24.9 and
      1.3 kcal/mol respectively, as calculated with the SMD-M06 approach. The
      theoretically predicted B(AC)2-1 mechanism is in good agreement with the
      experiment.

PMID- 22954290
TI  - Role of miRNA and cancer stem cells in chemoresistance and pancreatic cancer
      treatment.

PMID- 22954292
TI  - Evidence-based cytology in veterinary medicine: progress and opportunities.

PMID- 22954293
TI  - Use of the agarose cell block technique in veterinary diagnostic cytopathology:
      an "old and forgotten" method.

PMID- 22954294
TI  - Quantifying bovine insulin: conversion of units.

PMID- 22954295
TI  - Hemato--going--going--gone!

PMID- 22954296
TI  - Validation of Advia plateletcrit for assessing platelet mass in dogs, including
      Cavalier King Charles spaniels.
AB  - BACKGROUND: Determination of the plateletcrit (PCT) is the most effective way to
      evaluate platelet mass in dogs, such as Cavalier King Charles spaniel (CKCS)
      dogs, with macrothrombocytopenia. The IDEXX VetAutoread hematology analyzer,
      which performs quantitative buffy coat (QBC) analysis, has been validated to
      determine platelet mass in CKCS dogs. The Advia 2120 reports a PCT, but the
      validity of this value has not been evaluated for dogs with
      macrothrombocytopenia. OBJECTIVES: The goal of this study was to validate MPV and
      PCT determined by the Advia 2120 in dogs, including CKCS dogs, comparing values
      with those obtained from QBC analysis. METHODS: Advia PCT was compared with QBC
      results from 43 CKCS dogs and 15 dogs of other breeds in one study. Advia PCT,
      platelet count, and MPV were evaluated to identify biologic patterns in 31
      clinically healthy CKCS dogs and 66 dogs of 3 other breeds and to generate values
      used for comparisons. RESULTS: Advia PCT agreed well with QBC results in general,
      but had a negative bias and appeared to underestimate PCT in CKCS dogs with the
      lowest PCTs. Advia PCT and MPV results followed expected biologic patterns in
      CKCS dogs and dogs of other breeds with MPVs being highest in dogs with the
      lowest platelet counts. CONCLUSIONS: Advia 2120 PCT and MPV satisfactorily
      identified changes in platelet mass and size in CKCS dogs, but PCTs were lower
      than expected, especially in CKCS dogs with the lowest PCTs, when compared with
      QBC results.

PMID- 22954297
TI  - Cytochemical and immunocytochemical characterization of blood cells and
      immunohistochemical analysis of spleen cells from 2 species of frog, Rana
      (Aquarana) catesbeiana and Xenopus laevis.
AB  - BACKGROUND: Mechanisms of amphibian diseases are not characterized as well as
      those in domestic mammalian species. Antemortem laboratory testing is limited in
      frogs, presenting a diagnostic challenge to zoos, laboratories, and exotic
      veterinarians. OBJECTIVE: This study aimed to characterize blood cells and
      splenic cells from 2 anuran species based on characteristics identified by Wright
      staining, cytochemical staining, and immunochemical analysis and on histologic
      examination of spleens. METHODS: Blood specimens and spleens were obtained from 2
      species of frog, the American bullfrog (Rana [Aquarana] catesbeiana) and the
      African clawed frog (Xenopus laevis). Blood smears were evaluated after Wright
      staining and cytochemical staining for alpha-naphthyl butyrate esterase (NBE),
      chloroacetate esterase (CAE), myeloperoxidase (PER), Sudan black B (SBB), and
      leukocyte alkaline phosphatase (LAP) reactions and for immunoreactivity for
      antibodies against CD3epsilon, CD79a, and BLA.36 antigens. Histologic sections of
      spleen were evaluated after staining with H&E and for immunoreactivity for
      CD3epsilon, CD79a, and BLA.36 antigens. RESULTS: In bullfrogs, neutrophils,
      eosinophils, and monocytes were positive for some or all of the following: NBE,
      CAE, PER, and SBB; lymphocytes occasionally were positive for CAE. In clawed
      frogs, neutrophils, basophils, and monocytes were positive for some or all of the
      following: NBE, CAE, PER, and SBB; eosinophils occasionally were positive for CAE
      and PER, and lymphocytes were negative for all cytochemical stains. LAP was not a
      useful marker for any leukocyte type. In both species, peripheral blood
      lymphocytes were strongly immunoreactive for CD3epsilon, CD79a, and BLA.36. In
      splenic tissue, histologic patterns varied and there was diffuse immunoreactivity
      for CD79a and BLA.36 with focal reactivity for CD3epsilon, but with different
      distribution patterns in each species. CONCLUSION: Cytochemical and
      immunochemical analysis of cells may be helpful in identification and
      characterization of amphibian blood cells and splenic cells for evaluation of the
      health of these animals.

PMID- 22954299
TI  - Cytologic features of normal canine ovaries in different stages of estrus with
      histologic comparison.
AB  - BACKGROUND: Cytologic evaluation plays an important role in the diagnosis of
      ovarian neoplasia in dogs, but is supported by only scant information on
      cytologic features of canine ovaries. OBJECTIVE: The aim of this study was to
      provide detailed cytologic descriptions of normal canine ovaries in different
      stages of estrus with comparison to histologic features. METHODS: Client-owned
      dogs admitted for elective ovariohysterectomy were studied. For each dog, fine
      needle aspirates of both ovaries were collected, stained, and examined and were
      compared with histologic sections of the same ovary. The stage of estrus was
      confirmed by examination of histologic sections and cytologic specimens of
      vaginal cells collected with swabs. RESULTS: Thirty-two ovaries from 16 dogs were
      examined. Luteal cells were observed in 82% of the dogs in diestrus. In early
      diestrus these cells were polygonal with amphophilic to deeply basophilic
      cytoplasm, and in late diestrus luteal cells had blebbed cell borders and clear
      cytoplasm with numerous small vacuoles. Perivascular arrangements and leuko
      emperipolesis were noted in both phases of diestrus. Granulosa cells and spindle
      cells were found in cytologic specimens from most of the ovaries, and blue-gray
      extracellular material, sometimes associated with granulosa cells, was present.
      Medium-sized discrete round cells of undetermined origin were observed in some
      stages of estrus, and structures classified as corpora albicans were noted
      occasionally. CONCLUSIONS: Knowledge of specific cytologic features of normal
      canine ovaries is important for identification of pathologic processes in this
      organ. The novel findings of luteal cell emperipolesis, extracellular material
      associated with granulosa cells, and round cells of undetermined lineage warrant
      further study, which may provide new information on canine ovarian structure and
      function.

PMID- 22954298
TI  - Canine Trypanosoma evansi infection introduced into Germany.
AB  - A 9-year-old male Jack Russell Terrier with a history of travel to Thailand was
      presented with chronic lethargy, weight loss, unilateral anterior uveitis,
      pancytopenia, hyperglobulinemia, and proteinuria. Numerous trypomastigotes were
      found on a blood smear, and using molecular methods the parasite was identified
      as Trypanosoma evansi. After initial response to treatment, the dog experienced a
      relapse with central neurologic signs 88 days after initial presentation and
      died. Antibodies to T evansi were detected in both serum and cerebrospinal fluid
      (CSF) using a card agglutination test (CATT/T evansi), and PCR analysis of CSF
      for T evansi was positive. Findings at necropsy included marked non-purulent
      meningoencephalitis. Chronic infection with T evansi in a dog that returned to
      Germany following international travel highlights the risk associated with
      introduction of foreign animal diseases to Europe and the possibility of these
      infections becoming endemic. Detection of chronic infection and curative therapy
      of trypanosomiasis are challenging, and infection is usually fatal in the dog.

PMID- 22954300
TI  - Adenocarcinoma of the parotid salivary gland in a cow.
AB  - A 6-year-old Girolando dairy cow was presented for evaluation of a large
      subcutaneous facial mass. Fine-needle aspirates of the mass contained many
      neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and
      loosely cohesive clusters with streaming erythrocytes and neutrophils in the
      background. Neoplastic cells were 13-25 MUm in diameter and were round to
      cuboidal with variably distinct borders. Based on the signalment, anatomic
      location, and cytologic findings, differential diagnoses included salivary
      adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow
      was euthanized and a necropsy was performed. The primary neoplasm arose from the
      left parotid salivary gland and meastatic tumor was found in the regional lymph
      nodes and lung. Histologically, the tumor was composed of anastomosing and
      irregular solid islets surrounded by scant stroma. Cells were negative for
      periodic acid-Schiff (PAS), PAS-diastase, and Alcian blue pH 2.5 stains, used to
      detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland
      cells expressed cytokeratin, but not S100, alpha-smooth muscle actin, or
      vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The
      final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.

PMID- 22954301
TI  - The role of protease-activated receptor-2 on pulmonary neutrophils in the innate
      immune response to cockroach allergen.
AB  - BACKGROUND: Serine proteases in German cockroach (GC) have been shown to mediate
      allergic airway inflammation through the activation of protease activated
      receptor (PAR)-2. Neutrophils play an important role in regulating the innate
      immune response, and are recruited into the airways following GC frass exposure.
      As such, we investigated the role of PAR-2 in airway neutrophil recruitment,
      activation and cytokine production following allergen exposure. METHODS: Wild
      type and PAR-2-deficient mice were administered a single intratracheal
      instillation of PBS or GC frass and neutrophil recruitment, expression of PAR-2,
      CD80, CD86, and MHC class II were assessed by flow cytometry and levels of tumor
      necrosis factor (TNF)alpha was assessed by ELISA. Uptake of AlexaFluor 405
      labeled GC frass by neutrophils was performed by flow cytometry. RESULTS:
      Neutrophil recruitment in the lung and airways following GC frass exposure was
      significantly decreased in PAR-2-deficient mice compared to wild type mice. GC
      frass exposure increased the level of PAR-2 on pulmonary neutrophils and
      increased numbers of PAR-2-positive neutrophils were found in the lungs; however
      PAR-2 did not play a role in meditating allergen uptake. Comparing wild type and
      PAR-2-deficient mice, we found that a single exposure to GC frass increased
      levels of CD80 and CD86 on pulmonary neutrophils, an effect which was independent
      of PAR-2 expression. Neutrophils isolated from the whole lungs of naive PAR-2
      deficient mice treated ex vivo with GC frass produced significantly less TNFalpha
      than in similarly treated wild type neutrophils. Lastly, neutrophils were
      isolated from the bronchoalveolar lavage fluid of wild type and PAR-2-deficient
      mice following a single intratracheal exposure to GC frass. Airway neutrophils
      from PAR-2-deficient mice released substantially decreased levels of TNFalpha,
      suggesting a role for PAR-2 in neutrophil-derived cytokine production.
      CONCLUSIONS: Together these data suggest PAR-2 expression can be upregulated on
      lung neutrophils following allergen exposure and the consequence is altered
      release of TNFalpha which could drive the early innate immune response.

PMID- 22954302
TI  - Comparison of point estimates and average thicknesses of retinal layers measured
      using manual optical coherence tomography segmentation for quantification of
      retinal neurodegeneration in multiple sclerosis.
AB  - PURPOSE: The advent of macular optical coherence tomography (OCT) segmentation
      has enabled the in vivo quantitative assessment of retinal axonal and neuronal
      subpopulations. Recent studies employing OCT in multiple sclerosis (MS) have
      utilized various manual macular segmentation approaches to quantify retinal layer
      thicknesses. We investigated whether measurements of retinal layers solely at the
      points of maximal macular thickness (point estimates) within the central macular
      B-scan are representative of the corresponding average layer thicknesses for the
      ganglion cell + inner plexiform (GCIP) layers, inner nuclear layer (INL), outer
      plexiform layer (OPL) and outer nuclear layer (ONL) in MS and healthy controls.
      Additionally, we examined the correlation of manual segmentation-derived measures
      of composite layers with average thickness measures derived from automated 3-D
      segmentation of the macular cube. MATERIALS AND METHODS: Spectral-domain OCT
      central macular B-scans of 52 MS patients and 30 healthy controls (HCs) were
      manually segmented. Average layer thicknesses and layer thicknesses at the points
      of maximal macular thickness were calculated. Macular cube scans were also
      segmented utilizing a fully automated 3-D segmentation algorithm. RESULTS: GCIP,
      INL and OPL maximal thicknesses derived from point estimates correlated well with
      the average thicknesses of these layers within the central macular B-scan,
      whereas the ONL maximal thickness did not correlate as strongly. Manual
      segmentation-derived point estimates and average thickness measures of the GCIP
      correlated excellently with corresponding automated segmentation-derived
      measures. MS patients had significantly decreased GCIP maximal and average
      thicknesses relative to HCs. ONL average thickness was significantly decreased in
      MS compared to HCs, but this was not true of the ONL maximal thickness.
      CONCLUSIONS: GCIP, INL and OPL maximal layer thicknesses may be used as
      surrogates to assess the gross structural integrity of these layers in MS, in a
      time-conservative fashion.

PMID- 22954303
TI  - miRNAs associated with chemo-sensitivity in cell lines and in advanced bladder
      cancer.
AB  - BACKGROUND: MicroRNA is a naturally occurring class of non-coding RNA molecules
      that mediate posttranscriptional gene regulation and are strongly implicated in
      cellular processes such as cell proliferation, carcinogenesis, cell survival and
      apoptosis. Consequently there is increasing focus on miRNA expression as
      prognostic factors for outcome and chemotherapy response. Only approximately 50%
      of patients with bladder cancer respond to chemotherapy. Therefore, predictive
      markers, such as miRNAs, that can identify subgroups of patients who will benefit
      from chemotherapy will have great value for treatment guidance. METHODS: We
      profiled the expression of 671 miRNAs in formalin fixed paraffin embedded tumors
      from patients with advanced bladder cancer treated with cisplatin based
      chemotherapy. We delineated differentially expressed miRNAs in tumors from
      patients with complete response vs. patients with progressive disease and in
      tumors form patients with short and long overall survival time. Furthermore, we
      studied the effect of up- and down regulation of key miRNAs on the cisplatin
      sensitivity in eight bladder cancer cell lines with different sensitivities to
      cisplatin. RESULTS: miRNA expression profiling identified 15 miRNAs that
      correlated with response to chemotherapy and 5 miRNAs that correlated with
      survival time. Three miRNAs were associated with both response and survival (886
      3p, 923, 944). By changing the cellular level of the response-identified miRNAs
      in eight bladder cell lines with different cisplatin sensitivity we found that
      down-regulation of miR-27a, miR296-5p and miR-642 generally reduced the cell
      viability, whereas up-regulation of miR-138 and miR-886-3p reduced the viability
      of more than half of the cell lines. Decreasing miR-138 increased the cisplatin
      sensitivity in half of the cell lines and increasing miR-27a and miR-642
      generally increased cisplatin sensitivity. CONCLUSIONS: MiRNAs seem to be
      involved in cisplatin based chemo response and may form a new target for therapy
      and serve as biomarkers for treatment response.

PMID- 22954304
TI  - Migration experiences, employment status and psychological distress among Somali
      immigrants: a mixed-method international study.
AB  - BACKGROUND: The discourse about mental health problems among migrants and
      refugees tends to focus on adverse pre-migration experiences; there is less
      investigation of the environmental conditions in which refugee migrants live, and
      the contrasts between these situations in different countries. This cross
      national study of two samples of Somali refugees living in London (UK) and
      Minneapolis, Minnesota, (USA) helps to fill a gap in the literature, and is
      unusual in being able to compare information collected in the same way in two
      cities in different countries. METHODS: There were two parts to the study, focus
      groups to gather in-depth qualitative data and a survey of health status and
      quantifiable demographic and material factors. Three of the focus groups involved
      nineteen Somali professionals and five groups included twenty-eight lay Somalis
      who were living in London and Minneapolis. The quantitative survey was done with
      189 Somali respondents, also living in London and Minneapolis. We used the MINI
      International Neuropsychiatric Interview (MINI) to assess ICD-10 and DSM-IV
      mental disorders. RESULTS: The overall qualitative and quantitative results
      suggested that challenges to masculinity, thwarted aspirations, devalued refugee
      identity, unemployment, legal uncertainties and longer duration of stay in the
      host country account for poor psychological well-being and psychiatric disorders
      among this group. CONCLUSION: The use of a mixed-methods approach in this
      international study was essential since the quantitative and qualitative data
      provide different layers and depth of meaning and complement each other to
      provide a fuller picture of complex and multi-faceted life situations of refugees
      and asylum seekers. The comparison between the UK and US suggests that greater
      flexibility of access to labour markets for this refugee group might help to
      promote opportunities for better integration and mental well-being.

PMID- 22954305
TI  - Analysis of phosphopeptide changes as spermatozoa acquire functional competence
      in the epididymis demonstrates changes in the post-translational modification of
      Izumo1.
AB  - Spermatozoa are functionally inert when they emerge from the testes. Functional
      competence is conferred upon these cells during a post-testicular phase of sperm
      maturation in the epididymis. Remarkably, this functional transformation of
      epididymal spermatozoa occurs in the absence of nuclear gene transcription or
      protein translation. To understand the cellular mechanisms underpinning
      epididymal maturation, we have performed a label-free, MS-based, comparative
      quantification of peptides from caput, corpus and caudal epididymal spermatozoa.
      In total, 68 phosphopeptide changes could be detected during epididymal
      maturation corresponding to the identification of 22 modified proteins. Included
      in this list are the sodium-bicarbonate cotransporter, the sperm specific serine
      kinase 1, AKAP4 and protein kinase A regulatory subunit. Furthermore, four
      phosphopeptide changes came from Izumo1, the sperm-egg fusion protein, in the
      cytoplasmic segment of the protein. 2D-PAGE confirmed that Izumo1 is post
      translationally modified during epididymal transit. Interestingly,
      phosphorylation on Izumo1 was detected on residue S339 in the caput and corpus
      but not caudal cells. Furthermore, Izumo1 exhibited four phosphorylated residues
      when spermatozoa reached the cauda, which were absent from caput cells. A model
      is advanced suggesting that these phospho-regulations are likely to act as a
      scaffold for the association of adaptor proteins with Izumo1 as these cells
      prepare for fertilization.

PMID- 22954306
TI  - Stibonium ions for the fluorescence turn-on sensing of F- in drinking water at
      parts per million concentrations.
AB  - The 9-anthryltriphenylstibonium cation, [1](+), has been synthesized and used as
      a sensor for the toxic fluoride anion in water. This stibonium cation complexes
      fluoride ions to afford the corresponding fluorostiborane 1-F. This reaction,
      which occurs at fluoride concentrations in the parts per million range, is
      accompanied by a drastic fluorescence turn-on response. It is also highly
      selective and can be used in plain tap water or bottled water to test
      fluoridation levels.

PMID- 22954307
TI  - Gold nanoparticles as an HIV entry inhibitor.
AB  - Gold nanoparticles stabilized with polyethylene glycol were used to study their
      cytotoxicity and antiviral activity against HIV-1 in the laboratory. The HeLa-CD4
      LTR-B-gal cell line was used with gold nanoparticles to determine the cell
      viability using luminescent assay. The 50% cytotoxicity concentration, IC50 of
      gold nanoparticles was found to be 1.12+/-0.05 mg/ml. M-tropic, T-tropic, dual
      tropic and resistant isolates were inhibited by gold nanoparticles and their
      inhibition concentration ranged from 0.05 to 0.12 mg/ml. The mechanism of gold
      nanoparticles against HIV-1 is not clear but it inhibits the HIV-1 fusion. In
      this study, the gold nanoparticles were used to analyze their mode of antiviral
      activity and the experimental results showed that they inhibit the viral entry by
      binding with gp120 and prevent CD4 attachment. These properties of gold
      nanoparticles make them as an effective antiviral inhibitor.

PMID- 22954308
TI  - HIV gp120 is an aberrant chemoattractant for blood resting CD4 T cells.
AB  - Binding of HIV gp120 to the chemokine coreceptor CXCR4 mediates signal
      transduction that promotes actin dynamics critical for the establishment of viral
      latency in resting CD4 T cells. To some extent, this gp120-mediated signal
      transduction resembles the chemotactic response mediated by chemokines such as
      the stromal cell-derived factor-1 alpha (SDF-1). It has been suggested that gp120
      functions as a bona fide chemokine to attract or repel blood CD4 T cells. To
      determine whether gp120 is a viral chemoattractant, we compared the chemotactic
      properties of gp120 with those of SDF- 1, and confirmed previous observations
      that gp120 possesses some chemotactic ability at certain dosages. However, when
      we examined gp120 in a range of dosages, we found that in general, gp120 only
      attracts or repels blood resting CD4 T cells at a low level, and there is no
      clear pattern of dosage-dependency as normally seen in a typical chemokine. These
      irregularities of gp120 were observed in multiple donors. Nevertheless, gp120
      aberrantly interferes with SDF-1-mediated T cell chemotaxis and cell migration.
      These results suggest that gp120 does not act like a typical chemoattractant,
      although it triggers actin dynamics to facilitate HIV infection.

PMID- 22954309
TI  - Partial protection of SHIV-infected Chinese rhesus macaques against super
      infection with heterologous SHIV isolate.
AB  - BACKGROUND: Many studies have revealed a protective effect of infection with
      simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV)
      against subsequent infection by a related immunodeficiency virus. However,
      whether a protective response can be induced by an infection with an
      immunodeficiency virus is still currently debated in the HIV-1 vaccine field. The
      aim of this study was to evaluate the protection against SHIV challenge in
      Chinese macaques that had been inoculated with SHIVs containing different HIV-1
      envelops. METHODS: Eleven adult Chinese rhesus monkeys were inoculated with SHIV
      KB9, SHIV-1157ipd3N4 or SHIV-CN97001. After 30 weeks, the animals were exposed to
      SHIV-KB9 or SHIV-CN97001, which carried a heterologous envelope protein relative
      to the first challenge strain. Infection was monitored by measuring viral load
      and antibody response, as well as viral genome sequence analyses. RESULTS: After
      first challenge, all the monkeys demonstrated high viral loads and specific
      antibody responses. Protection from super-infection was statistically significant
      in all the animals inoculated with SHIV-KB9 or SHIV-1157ipd3N4. However, animals
      inoculated with SHIV-CN97001 and challenged with SHIV-KB9 showed new infections.
      The susceptibility to super-infection was not correlated with neutralizing
      antibodies present at the time of exposure to the second virus. CONCLUSIONS:
      These findings indicate that different SHIV infection may confer different levels
      of protection against a second SHIV infection in Chinese monkeys. Understanding
      this protective response in SHIV infected macaques may shed a new light on HIV-1
      vaccine development.

PMID- 22954310
TI  - Structure and organization of the mitochondrial DNA control region with tandemly
      repeated sequence in the Amazon ornamental fish.
AB  - Tandemly repeated sequences are a common feature of vertebrate mitochondrial DNA
      control regions. However, questions still remain about their mode of evolution
      and function. To better understand patterns of variation in length and to explore
      the existence of previously described domain, we have characterized the control
      region structure of the Amazonian ornamental fish Nannostomus eques and
      Nannostomus unifasciatus. The control region ranged from 1121 to 1142 bp in
      length and could be separated into three domains: the domain associated with the
      extended terminal associated sequences, the central conserved domain, and the
      conserved sequence blocks domain. In the first domain, we encountered a sequence
      repeated 10 times in tandem (variable number tandem repeat (VNTR)) that could
      adopt an "inverted repetitions" type structural conformation. The results suggest
      that the VNTR pattern encountered in both N. eques and N. unifasciatus is
      consistent with the prerequisites of the illegitimate elongation model in which
      the unequal pairing of the chains near the 5'-end of the control region favors
      the formation of repetitions.

PMID- 22954312
TI  - Core-modified naphthalenediimides generate persistent radical anion and cation:
      new panchromatic NIR probes.
AB  - The generation of the first persistent radical cation of naphthalenediimide with
      Cu(2+)/Fe(3+) under ambient conditions is reported. An alternate anionic trigger
      generates a persistent radical anion within the same motif. Steric protection and
      H-bonding enhances the half-life of radical cation by 290-fold. The radical anion
      and cation have orthogonal spin density, panchromatic and NIR optical bands,
      which can be applied as attractive multichannel probes.

PMID- 22954313
TI  - Undecaphenylcorroles.
AB  - A first major study of undecaphenylcorrole (UPC) derivatives is presented. Three
      different Cu-UPC derivatives with different para substituents X (X = CF(3), H,
      CH(3)) on the beta-aryl groups were synthesized via Suzuki-Miyaura coupling of
      Cu[Br(8)TPC] and the appropriate arylboronic acid. A single-crystal X-ray
      structure of the X = CF(3) complex revealed a distinctly saddled macrocycle
      conformation with adjacent pyrrole rings tilted by ~60-66 degrees  relative to
      one another (within the dipyrromethane units), which is somewhat higher than that
      observed for beta-unsubstituted Cu-TPC derivatives but slightly lower than that
      observed for Cu[Br(8)TPC] (~70 degrees ) derivatives. Electrochemical and
      electronic absorption measurements afforded some of the first comparative
      insights into meso versus beta substituent effects on the copper corrole core.
      The Soret maxima of the Cu-UPC complexes (~440-445 nm), however, are comparable
      to those of Cu[Br(8)TPC] derivatives and are considerably red-shifted relative to
      Cu-TPC derivatives. Para substituents on the beta-phenyl groups were found to
      tune the redox potentials of copper corroles more effectively than those on meso
      phenyl substituents, a somewhat surprising observation given that neither the
      HOMO nor LUMO has significant amplitudes at the beta-pyrrolic positions.

PMID- 22954311
TI  - Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild
      cognitive impairment.
AB  - BACKGROUND: Anxiety, apathy and depression are common in subjects with mild
      cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We
      investigated whether these symptoms correlated with cerebrospinal fluid (CSF)
      markers for AD in subjects with MCI. Method Subjects with MCI (n=268) were
      selected from the 'Development of screening guidelines and criteria for pre
      dementia Alzheimer's disease' (DESCRIPA) and Alzheimer's Disease Neuroimaging
      Initiative (ADNI) studies. We measured amyloid beta(1-42) protein (Abeta42) and
      total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the
      Neuropsychiatric Inventory. RESULTS: Depressive symptoms were reported by 55
      subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The
      presence of anxiety was associated with abnormal CSF Abeta42 [odds ratio (OR)
      2.3, 95% confidence interval (CI) 1.6-3.3] and t-tau (OR 2.6, 95% CI 1.9-3.6)
      concentrations and with the combination of abnormal concentrations of both
      Abeta42 and t-tau (OR 3.1, 95% CI 2.0-4.7). The presence of agitation and
      irritability was associated with abnormal concentrations of Abeta42 (agitation:
      OR 1.6, 95% CI 1.1-2.3; irritability: OR 2.2, 95% CI 1.5-3.3). Symptoms of
      depression and apathy were not related to any of the CSF markers. CONCLUSIONS: In
      subjects with MCI, symptoms of anxiety, agitation and irritability may reflect
      underlying AD pathology, whereas symptoms of depression and apathy do not.

PMID- 22954314
TI  - Ab initio and density functional theory study of keto-enol equilibria of deltic
      acid in gas and aqueous solution phase: a bimolecular proton transfer mechanism.
AB  - Keto-enol tautomerism in deltic acid (2,3-dihydroxycycloprop-2-en-1-one) has been
      studied using ab initio methods and the B3LYP functional of density functional
      theory, as well as complete basis set (CBS-QB3 and CBS-APNO) and G4 methods.
      Relative and absolute energies were calculated with each of the methods, whereas
      computations of geometries and harmonic frequencies for dihydroxycyclopropenone
      and hydroxycyclopropanedione were computed in the gas phase but were limited to
      HF, MP2, and the B3LYP functional, in combination with the 6-31++G(3df,3pd) basis
      set. Using the MP2/6-31++G(3df,3pd) gas phase optimized structure, each species
      was then optimized fully in aqueous solution by using the polarizable continuum
      model (PCM) self-consistent reaction field approach, in which HF, MP2, and B3LYP
      levels of theory were utilized, with the same 6-31++G(3df,3pd) basis set. In both
      gas and aqueous solution phases, the keto form is higher in energy for all of the
      model chemistries considered. From the B3LYP/6-31++G(3df,3pd) Gibbs free energy,
      the keto-enol tautomeric equilibrium constant for 2,3-dihydroxycycloprop-2-en-1
      one/3-hydroxy-1,2-cyclopropanedione is computed to be K(T)(gas) = 2.768 * 10(-12)
      and K(T)(aq) = 5.469 * 10(-14). It is concluded that the enol form is
      overwhelmingly predominant in both environments.

PMID- 22954315
TI  - Inbreeding avoidance by recognition of close kin in the pea aphid, Acyrthosiphon
      pisum.
AB  - Inbreeding depression has detrimental effects on many organisms, but its effects
      are potentially greater in organisms that have at least one asexually reproducing
      life stage. Here, the existence of severe inbreeding depression upon selfing (r =
      1) in the cyclic parthenogenetic aphid Acyrthosiphon pisum (Harris) (Hemiptera:
      Aphididae) is documented. Egg hatching success and offspring survival of inbred
      mating pairs are significantly lower than that of outbred mating pairs. Two
      possible mechanisms for avoiding selfing are examined: avoidance of partners of
      identical genetic makeup and avoidance of partners of the same body color (as a
      proxy for genetic similarity). Mating between males and females of the same color
      was as successful as mating between partners of different colors. In contrast,
      the success of mating between close kin was consistently reduced compared to that
      of mating between genetically unrelated partners. Interestingly, mating between
      close kin proceeded normally until the very last stage of the mating process.
      Thus, inbreeding avoidance appears to take place sometime between copulation and
      sperm transfer, suggesting that cryptic female choice may play a role in the
      process.

PMID- 22954316
TI  - Rapid seeded growth of monodisperse, quasi-spherical, citrate-stabilized gold
      nanoparticles via H2O2 reduction.
AB  - In this report, we demonstrate a rapid and simple seeded growth method for
      synthesizing monodisperse, quasi-spherical, citrate-stabilized Au nanoparticles
      (Au NPs) via H(2)O(2) reduction of HAuCl(4). Au NPs with diameter ranging from 30
      to 230 nm can be synthesized by simply adding 12 nm citrate stabilized Au NP
      seeds to an aqueous solution of H(2)O(2) and HAuCl(4) under ambient conditions.
      The diameter of the resulting Au NPs can be quantitatively controlled by the
      molar ratio of HAuCl(4) to the Au seeds. The standard deviation of the Au NP
      sizes is less than 10%, and the ellipticity (ratio of major to minor axes) of the
      NPs is less than 1.1. Compared to existing ones, the present seeded growth
      approach is implemented within 1 min under ambient condition, and no unfavorable
      additives are involved because H(2)O(2) can readily decompose into H(2)O during
      storage or via boiling.

PMID- 22954317
TI  - CYP17A1 mutations identified in 17 Chinese patients with 17alpha
      hydroxylase/17,20-lyase deficiency.
AB  - CONTEXT: 17alpha-hydroxylase deficiency (17OHD) is a relatively rare disease,
      accounting for about 1% of congenital adrenal hyperplasia cases. The CYP17A1 gene
      mutation can lead to this disease. Human CYP17A1 gene is located on chromosome
      10q24.3. It consists of eight exons encoding 508 amino acids. To date, more than
      50 mutations in exons and introns of the CYP17A1 gene have been reported to cause
      complete or partial 17OHD. OBJECTIVE: The aim of this study was to investigate
      the CYP17A1 gene mutation types in 17 Chinese patients, containing 11 complete
      and six partial 17OHD patients. SETTING: We conducted the study in the Department
      of Obstetrics and Gynecology of Peking Union Medical College Hospital. PATIENTS:
      Seventeen patients were studied with complete or partial 17OHD. MAIN OUTCOME
      MEASURES: The CYP17A1 gene was sequenced and we measured steroid and sex hormone
      levels. RESULTS: Analysis of the CYP17A1 gene in our patients revealed 12
      different kinds of mutation. Two mutations (IVS1-1G>A and L209P) were novel
      mutations. Mutation c.985_987delTACinsAA (Y329KfsX418) in Exon 6 was the most
      common mutation in Chinese patients, accounting for 50 percents of the mutant
      alleles (17/34). Exon 6 was the hot spot since most mutations were detected in
      this exon (59%, 20/34 alleles). There was no mutation detected in the Exons 4 and
      5.

PMID- 22954318
TI  - Protective effects of hesperidin derivatives and their stereoisomers against
      advanced glycation end-products formation.
AB  - CONTEXT: Maillard reaction is implicated in the development of pathophysiology in
      age-related diseases. The search for newer Maillard reaction inhibitors is a
      priority among strategies to combat diabetes complications. OBJECTIVE: To
      evaluate the inhibitory potential of hesperidin, its derivatives and their
      stereoisomers against advanced glycation end-products (AGEs) formation. MATERIALS
      AND METHODS: Hesperidin and hesperetin were chirally separated and the inhibitory
      effects of 1:1 mixture of (2S)- and (2R)-hesperidin (1), (2S)-hesperidin (2),
      (2R)-hesperidin (3), 1:1 mixture of (S)- and (R)-hesperetin (4), (S)-hesperetin
      (5), (R)-hesperetin (6), and monoglucosyl hesperidin (7) [1:1 mixture of (2S)
      glucosyl hesperidin (8) and (2R)-glucosyl hesperidin (9)] at a concentration of 1
      mM on protein glycation reaction have been revealed using the newly constructed
      RNase A-methylglyoxal (MGO) assay for the early stage and the bovine serum
      albumin (BSA)-glucose assay for the late stage of Maillard reaction. RESULTS:
      This study has demonstrated that hesperidin and its derivatives possessed
      relatively strong activity against the formation of AGEs. (S)-Hesperetin (5)
      possessed the highest inhibitory rate up to 57.4% in BSA-glucose assay, 38.2% in
      RNase A-MGO assay. DISCUSSION AND CONCLUSION: The new RNase A-MGO assay system
      could be used for the screening of AGEs inhibitors and hesperidin, and its
      derivatives could be promising candidate adjuvants for the treatment of diabetes
      complication, and age-related chronic diseases.

PMID- 22954319
TI  - Automated platform for high-resolution tissue imaging using nanospray desorption
      electrospray ionization mass spectrometry.
AB  - An automated platform has been developed for acquisition and visualization of
      mass spectrometry imaging (MSI) data using nanospray desorption electrospray
      ionization (nano-DESI). The new system enables robust operation of the nano-DESI
      imaging source over many hours by precisely controlling the distance between the
      sample and the nano-DESI probe. This is achieved by mounting the sample holder
      onto an automated XYZ stage, defining the tilt of the sample plane, and
      recalculating the vertical position of the stage at each point. This approach is
      useful for imaging of relatively flat samples such as thin tissue sections.
      Custom software called MSI QuickView was developed for visualization of large
      data sets generated in imaging experiments. MSI QuickView enables fast
      visualization of the imaging data during data acquisition and detailed processing
      after the entire image is acquired. The performance of the system is demonstrated
      by imaging rat brain tissue sections. Low background noise enables simultaneous
      detection of lipids and metabolites in the tissue section. High-resolution mass
      analysis combined with tandem mass spectometry (MS/MS) experiments enabled
      identification of the observed species. In addition, the high dynamic range
      (>2000) of the technique allowed us to generate ion images of low-abundance
      isobaric lipids. A high-spatial resolution image was acquired over a small region
      of the tissue section revealing the distribution of an abundant brain metabolite,
      creatine, on the boundary between the white and gray matter. The observed
      distribution is consistent with the literature data obtained using magnetic
      resonance spectroscopy.

PMID- 22954320
TI  - Children in hospital in Ireland--what do they eat and what do they weigh: a cross
      sectional study.
AB  - Overweight and obesity is a growing problem in Ireland. Many parents are unaware
      when their child is overweight or obese. Our objectives were to examine parents'
      perceptions of a healthy diet and their children's BMI; and to evaluate the food
      offered to children in our paediatric in-patient unit. FINDINGS: A retrospective
      questionnaire was distributed to 95 patients and their families admitted over one
      month. Seventy-eight had BMI values calculated (42 males, 36 females). Twenty-one
      children (26.9%) were overweight/obese: 14/21 parents (66.7%) thought their child
      had a normal weight. Sixty percent of children served dinner in the hospital were
      given fried potatoes. Four had fruit/vegetables. Forty-six parents brought food
      into hospital, of these 14 brought purchased food. CONCLUSIONS: This study
      highlights the problem of child obesity in Ireland and parental underestimation
      of this problem. The nutritional value of food served to children in hospital
      needs to be improved and hospital admissions used as opportunities to promote
      healthy eating habits.

PMID- 22954322
TI  - Cytokine and chemokine secretion induced by poly(I:C) through NF-kappaB and
      phosphoinositide 3-kinase signaling pathways in human corneal fibroblasts.
AB  - PURPOSE/AIM: Viral infection of the cornea can result in inflammation and
      scarring and eventually lead to blindness. Polyinosinic-polycytidylic acid
      [poly(I:C)], an analog of viral double-stranded RNA, induces the secretion of
      cytokines and chemokines from cultured corneal fibroblasts. We have now
      investigated the role of nuclear factor (NF)-kappaB and phosphoinositide 3-kinase
      (PI3K) signaling pathways in poly(I:C)-induced cytokine and chemokine secretion
      from corneal fibroblasts. MATERIALS AND METHODS: Human corneal fibroblasts were
      cultured with poly(I:C) in the absence or presence of IKK-2 inhibitor or
      LY294002, which are inhibitors of NF-kappaB and PI3K signaling, respectively. The
      release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokines IL
      8, IP-10, and RANTES from the cells was measured with an enzyme-linked
      immunosorbent assay. RESULTS: Poly(I:C) induced the secretion of IL-6, IL-8, IP
      10, and RANTES from corneal fibroblasts. Whereas the poly(I:C)-induced secretion
      of IL-6, IP-10, and RANTES was inhibited by both IKK-2 inhibitor and LY294002,
      that of IL-8 was blocked only by IKK-2 inhibitor. CONCLUSIONS: The poly(I:C)
      induced secretion of IL-6, IP-10, and RANTES from human corneal fibroblasts is
      mediated by both NF-kappaB and PI3K signaling pathways, whereas that of IL-8 is
      mediated by the NF-kappaB pathway. These signaling pathways thus likely
      contribute to local inflammation in the corneal stroma induced by viral
      infection.

PMID- 22954323
TI  - Potentials and challenges in self-nanoemulsifying drug delivery systems.
AB  - INTRODUCTION: A significant number of new chemical entities (almost 40%), that
      are outcome of contemporary drug discovery programs, have a potential therapeutic
      promise for patient, as they are highly potent but poorly water soluble resulting
      in reduced oral bioavailability. Self-nanoemulsifying drug delivery systems
      (SNEDDS) have emerged as a vital strategy to formulate these poorly soluble
      compounds for bioavailability enhancement. AREAS COVERED: The review gives an
      insight about potential of SNEDDS with regards to oral drug delivery. The effect
      of various key constituents on formulation of SNEDDS and their applications in
      oral drug delivery is also discussed. Various aspects of formulation,
      characterization and biopharmaceutical aspects of SNEDDS are also been explored.
      The choice and selection of excipients for development of SNEDDS is also
      discussed. EXPERT OPINION: The ability of SNEDDS to present the drug in single
      unit dosage form either as soft or hard gelatin capsule with enhanced solubility
      maintaining the uniformity of dose is unique. With the ease of large-scale
      production, high drug-loading capacity, improvement in release behavior of poorly
      water-soluble drugs and improvement of oral bioavailability, SNEDDS have emerged
      as preferable system for the formulation of drug compounds with bioavailability
      problems due to poor aqueous solubility.

PMID- 22954324
TI  - Technical updates to basic proteins focalization using IPG strips.
AB  - BACKGROUND: Gel-based proteomic is a popular and versatile method of global
      protein separation and quantification. However, separation of basic protein still
      represents technical challenges with recurrent problems of resolution and
      reproducibility. RESULTS: Three different protocols of protein loading were
      compared using MCF7 cells proteins. In-gel rehydration, cup-loading and paper
      bridge loading were first compared using 6-11 IPG strips, as attempted, in-gel
      rehydration gave large horizontal steaking; paper-bridge loading displayed an
      interesting spot resolution, but with a predominant loss of material; cup-loading
      was selected as the most relevant method, but still needing improvement. Twelve
      cup-loading protocols were compared with various strip rehydration, and cathodic
      wick solutions. Destreak appeared as better than DTT for strip rehydration; the
      use of isopropanol gave no improvement. The best 2DE separation was observed with
      cathodic wicks filled with rehydration solution complemented with DTT. Paper
      bridge loading was finally analyzed using non-limited samples, such as bovine
      milk. In this case, new spots of basic milk proteins were observed, with or
      without paper wicks. CONCLUSION: According to this technical study of basic
      protein focalization with IPG strips, the cup-loading protocol clearly displayed
      the best resolution and reproducibility: strips were first rehydrated with
      standard solution, then proteins were cup-loaded with destreak reagent, and
      focalisation was performed with cathodic wicks filled with rehydration solution
      and DTT. Paper-bridge loading could be as well used, but preferentially with non
      limited samples.

PMID- 22954326
TI  - Macromolecular crowding and protein stability.
AB  - An understanding of cellular chemistry requires knowledge of how crowded
      environments affect proteins. The influence of crowding on protein stability
      arises from two phenomena, hard-core repulsions and soft (i.e., chemical)
      interactions. Most efforts to understand crowding effects on protein stability,
      however, focus on hard-core repulsions, which are inherently entropic and
      stabilizing. We assessed these phenomena by measuring the temperature dependence
      of NMR-detected amide proton exchange and used these data to extract the entropic
      and enthalpic contributions of crowding to the stability of ubiquitin. Contrary
      to expectations, the contribution of chemical interactions is large and in many
      cases dominates the contribution from hardcore repulsions. Our results show that
      both chemical interactions and hard-core repulsions must be considered when
      assessing the effects of crowding and help explain previous observations about
      protein stability and dynamics in cells.

PMID- 22954325
TI  - Resting heart rate and outcomes in patients with cardiovascular disease: where do
      we currently stand?
AB  - BACKGROUND: Data from large epidemiological studies suggest that elevated heart
      rate is independently associated with cardiovascular and all-cause mortality in
      patients with hypertension and in those with established cardiovascular disease.
      Clinical trial findings also suggest that the favorable effects of beta-blockers
      and other heart rate-lowering agents in patients with acute myocardial infarction
      and congestive heart failure may be, at least in part, due to their heart rate
      lowering effects. Contemporary clinical outcome prediction models such as the
      Global Registry of Acute Coronary Events (GRACE) score include admission heart
      rate as an independent risk factor. AIMS: This article critically reviews the key
      epidemiology concerning heart rate and cardiovascular risk, potential mechanisms
      through which an elevated resting heart rate may be disadvantageous and evaluates
      clinical trial outcomes associated with pharmacological reduction in resting
      heart rate. CONCLUSIONS: Prospective randomised data from patients with
      significant coronary heart disease or heart failure suggest that intervention to
      reduce heart rate in those with a resting heart rate >70 bpm may reduce
      cardiovascular risk. Given the established observational data and randomised
      trial evidence, it now appears appropriate to include reduction of elevated
      resting heart rate by lifestyle +/- pharmacological therapy as part of a
      secondary prevention strategy in patients with cardiovascular disease.

PMID- 22954327
TI  - Recent insights into plant-virus interactions through proteomic analysis.
AB  - Plant viruses represent a major threat for a wide range of host species causing
      severe losses in agricultural practices. The full comprehension of mechanisms
      underlying events of virus-host plant interaction is crucial to devise novel
      plant resistance strategies. Until now, functional genomics studies in plant
      virus interaction have been limited mainly on transcriptomic analysis. Only
      recently are proteomic approaches starting to provide important contributions to
      this area of research. Classical two-dimensional electrophoresis (2-DE) coupled
      to mass spectrometry (MS) is still the most widely used platform in plant
      proteome analysis, although in the last years the application of quantitative
      "second generation" proteomic techniques (such as differential in gel
      electrophoresis, DIGE, and gel-free protein separation methods) are emerging as
      more powerful analytical approaches. Apparently simple, plant-virus interactions
      reveal a really complex pathophysiological context, in which resistance, defense
      and susceptibility, and direct virus-induced reactions interplay to trigger
      expression responses of hundreds of genes. Given that, this review is
      specifically focused on comparative proteome-based studies on pathogenesis of
      several viral genera, including some of the most important and widespread plant
      viruses of the genus Tobamovirus, Sobemovirus, Cucumovirus and Potyvirus. In all,
      this overview reveals a widespread repression of proteins associated with the
      photosynthetic apparatus, while energy metabolism/protein synthesis and turnover
      are typically up-regulated, indicating a major redirection of cell metabolism.
      Other common features include the modulation of metabolisms concerning sugars,
      cell wall, and reactive oxigen species as well as pathogenesis-related (PR)
      proteins. The fine-tuning between plant development and antiviral defense
      mechanisms determines new patterns of regulation of common metabolic pathways. By
      offering a 360-degree view of protein modulation, all proteomic tools reveal the
      extraordinary intricacy of mechanisms with which a simple viral genome perturbs
      the plant cell molecular networks. This "omic" approach, while providing a global
      perspective and useful information to the understanding of the plant host-virus
      interactome, may possibly reveal protein targets/markers useful in the design of
      future diagnosis and/or plant protection strategies.

PMID- 22954328
TI  - The immune response to tuberculosis infection in the setting of Helicobacter
      pylori and helminth infections.
AB  - We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis
      (TB)-endemic countries to evaluate whether cytokine responses to latent TB
      infection (LTBI) are modified in the setting of concurrent H. pylori and helminth
      infection. As measured by the Quantiferon-TB GOLD interferon-gamma release assay,
      a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori
      seropositive and/or helminth infected. Relative to ten subjects with LTBI only,
      16 subjects with concurrent H. pylori infection had significantly elevated levels
      of IFN-gamma, and nine subjects with both H. pylori and helminth infection had
      significantly elevated levels of IFN-gamma, IL-2, IL-13, and IL-5. H. pylori is
      associated with enhanced IFN-gamma responses to TB, even in the setting of
      concurrent helminth infection. Efficacy of TB vaccines may vary with the co
      existence of these three infections in the developing world.

PMID- 22954329
TI  - Conservative treatment, plate fixation, or prosthesis for proximal humeral
      fracture. A prospective randomized study.
AB  - BACKGROUND: Proximal humerus fracture is the third most common fracture type
      after hip and distal radius fracture in elderly patients. A comprehensive study
      by Palvanen et al. demonstrated an increase in the annual fracture rate of 13.7%
      per year over the past 33 years. Should this trend continue, the fracture rate
      would triple over the next three decades. The increasing incidence of low-energy
      fractures raises questions about the optimal treatment in terms of functional
      outcome, pain, and rehabilitation time, as well as the economical impact. Despite
      the high incidence and costs of proximal humerus fractures, there is currently no
      valid scientific evidence for the best treatment method. Several publications,
      including a Cochrane review outline the need for high-quality, well-designed
      randomized controlled trials. METHODS/DESIGN: The study is a prospective,
      randomized, national multi-center trial. The hypothesis of the trial is that
      surgical treatment of displaced proximal humerus fractures achieves better
      functional outcome, pain relief, and patient satisfaction compared to
      conservative treatment. The trial is designed to compare conservative and
      surgical treatment of proximal humerus fractures in patients 60 years and older.
      The trial includes two strata. Stratum I compares surgical treatment with locking
      plates to conservative treatment for two-part fractures. Stratum II compares
      multi-fragmented fractures, including three- and four-part fractures. The aim of
      Stratum II is to compare conservative treatment, surgical treatment with the
      Philos locking plate, and hemiarthroplasty with an Epoca prosthesis. The primary
      outcome measure will be the Disabilities of the Arm, Shoulder and Hand (DASH)
      score and the secondary outcome measures will be the EuroQol-5D (EQ-5D) value,
      OSS, Constant-Murley Score, VAS, and 15D.Recruiting time will be 3 years. The
      results will be analyzed after the 2-year follow-up period. DISCUSSION: This
      publication presents a prospective, randomized, national multi-center trial. It
      gives details of patient flow, randomization, aftercare and also ways of analysis
      of the material and ways to present and publish the results. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01246167.

PMID- 22954330
TI  - Crystal structure and computational investigation of an analogue of Grubbs'
      second generation catalyst with a fluorous phosphine.
AB  - A fluorous phosphine analogue of Grubbs' second generation olefin metathesis
      catalyst, (H(2)IMes)((R(f8)(CH(2))(2))(3)P)(Cl)(2)Ru(=CHPh) (1; H(2)IMes/R(f8) =
      1,3-dimesityl-4,5-dihydroimidazol-2-ylidene/(CF(2))(7)CF(3)) is crystallized and
      the X-ray structure analyzed in detail. The bond lengths and angles about
      ruthenium are compared to those of two solvates and five derivatives of Grubbs'
      second generation catalyst. All exhibit distorted square pyramidal geometries in
      which the alkylidene ligands occupy apical positions, and geometric trends are
      interpreted with the help of density functional calculations. The perfluoroalkyl
      groups (1) exhibit helical conformations, as manifested by various torsional
      relationships, (2) segregate in the lattice, and (3) align in pairs of opposite
      helical chiralities.

PMID- 22954332
TI  - UV-laser photochemistry of isoxazole isolated in a low-temperature matrix.
AB  - The photochemistry of matrix-isolated isoxazole, induced by narrowband tunable UV
      light, was investigated by infrared spectroscopy, with the aid of MP2/6
      311++G(d,p) calculations. The isoxazole photoreaction starts to occur upon
      irradiation at lambda = 240 nm, with the dominant pathway involving decomposition
      to ketene and hydrogen cyanide. However, upon irradiation at lambda = 221 nm, in
      addition to this decomposition, isoxazole was also found to isomerize into
      several products: 2-formyl-2H-azirine, 3-formylketenimine, 3
      hydroxypropenenitrile, imidoylketene, and 3-oxopropanenitrile. The structural and
      spectroscopic assignment of the different photoisomerization products was
      achieved by additional irradiation of the lambda = 221 nm photolyzed matrix,
      using UV-light with lambda >= 240 nm: (i) irradiation in the 330 <= lambda <= 340
      nm range induced direct transformation of 2-formyl-2H-azirine into 3
      formylketenimine; (ii) irradiation with 310 <= lambda <= 318 nm light induced the
      hitherto unobserved transformation of 3-formylketenimine into 3
      hydroxypropenenitrile and imidoylketene; (iii) irradiation with lambda = 280 nm
      light permits direct identification of 3-oxopropanenitrile; (iv) under lambda =
      240 nm irradiation, tautomerization of 3-hydroxypropenenitrile to 3
      oxopropanenitrile is observed. On the basis of these findings, a detailed
      mechanistic proposal for isoxazole photochemistry is presented.

PMID- 22954331
TI  - Resistance mechanisms to chlorpyrifos and F392W mutation frequencies in the
      acetylcholine esterase ace1 allele of field populations of the tobacco whitefly,
      Bemisia tabaci in China.
AB  - The tobacco whitefly B-biotype Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae)
      is a worldwide pest of many crops. In China, chlorpyrifos has been used to
      control this insect for many years and is still being used despite the fact that
      some resistance has been reported. To combat resistance and maintain good control
      efficiency of chlorpyrifos, it is essential to understand resistance mechanisms.
      A chlorpyrifos resistant tobacco whitefly strain (NJ-R) and a susceptible strain
      (NJ-S) were derived from a field-collected population in Nanjing, China, and the
      resistance mechanisms were investigated. More than 30-fold resistance was
      achieved after selected by chlorpyrifos for 13 generations in the laboratory.
      However, the resistance dropped significantly to about 18-fold in only 4
      generations without selection pressure. Biochemical assays indicated that
      increased esterase activity was responsible for this resistance, while
      acetylcholine esterase, glutathione S-transferase, and microsomal-O-demethylase
      played little or no role. F392W mutations in acel were prevalent in NJ-S and NJ-R
      strains and 6 field-collected populations of both B and Q-biotype from locations
      that cover a wide geographical area of China. These findings provide important
      information about tobacco whitefly chlorpyrifos resistance mechanisms and
      guidance to combat resistance and optimize use patterns of chlorpyrifos and other
      organophosphate and carbamate insecticides.

PMID- 22954333
TI  - Fluorogenic quantum dot-gold nanoparticle assembly for beta secretase inhibitor
      screening in live cell.
AB  - We have developed a novel fluorogenic nanoprobe prepared from the assembly of
      CdSe/ZnS quantum dot (QD) and gold (Au) nanoparticles in which QD was conjugated
      with a specifically designed beta-secretase (BACE1) substrate peptide, which was
      allowed to bind to the Ni-nitrilotriacetate (Ni-NTA) modified Au nanoparticles.
      This coordination-mediated binding of the QD with Au nanoparticles via Ni-NTA
      histidine (His) interaction resulted in highly efficient quenching of QD
      fluorescence through a distance-dependent fluorescence resonance energy transfer
      (FRET) phenomenon. The prequenched QD-Au assembly recovered the fluorescence in
      the presence of the BACE1 enzyme after incubation in vitro. The high quenching
      efficiency of AuNP and robust QD fluorescence signal recovery upon BACE1
      enzymatic digestion enabled us to visualize BACE1 activity in living cells, which
      further allowed us to generate the half maximal inhibitory concentration (IC(50))
      values for BACE1 inhibitors in the cell-based assay utilizing a high throughput
      system (HTS). These results suggest the potential application of QD-AuNP assembly
      toward the HTS drug screening system as a robust and efficient probe to identify
      active molecules in BACE1-related diseases such as Alzheimer's disease.

PMID- 22954334
TI  - Prevalence of hepatitis 'B' and hepatitis 'C' among preoperative cataract
      patients in Karachi.
AB  - BACKGROUND: To report the findings of preoperative screening regarding prevalence
      of hepatitis B and hepatitis C in patients presenting for cataract surgery.
      FINDINGS: A descriptive study was conducted among 377 patients presenting for
      cataract surgery to Department of Ophthalmology Unit I, CHK from April 2010 to
      May 2011. Convenience sampling was done to recruit the participants aged 18 years
      and above. The patients were screened for hepatitis B and C infections and
      findings were recorded on a structured compilation sheet.The total prevalence of
      both hepatitis B and hepatitis C in preoperative Cataract patients was found to
      be 49 out of 377(12.99%). Overall, 8 out of 377 (2.1%) patients were HBsAg
      positive and 42 out of 377 (11.1%) were Anti-HCV positive. Only 1 patient was
      found with a co-infection with both HBsAg and Anti-HCV positive. CONCLUSIONS:
      High proportions of hepatitis B and C are reported among preoperative cataract
      patients of Karachi. Routine serological screening prior to surgery should be
      made mandatory so that asymptomatic patients would no longer pose a threat to its
      spread.

PMID- 22954335
TI  - In situ STM investigation of aromatic poly(azomethine) arrays constructed by "on
      site" equilibrium polymerization.
AB  - Two-dimensional (2D) arrays of pi-conjugated aromatic polymers produced by
      surface-selective Schiff base coupling reactions between an aromatic diamine and
      an aromatic dialdehyde were investigated in detail using in situ scanning
      tunneling microscopy. Surface-selective coupling was achieved for almost all
      diamine/dialdehyde combinations attempted, although several combinations did not
      proceed even in homogeneous aqueous alkaline solution. Most of the combinations
      of an aromatic diamine and a dialdehyde, except the combinations of 4,4'
      azodianiline with mono/bithiophenedicarboxaldehyde, formed highly ordered pi
      conjugated polymer arrays on an iodine-modified Au(111) surface in aqueous
      solution at a suitable pH. The simplest polymer of the various combinations
      tested, obtained from the combination of 1,4-diaminobenzene with
      terephthaldicarboxaldehyde, gave a 2D array consisting of linearly connected
      benzene units. Poly(azomethine) adlayers caused a positive shift in the
      electrochemical potential of the butterfly shaped oxidative adsorption and
      reductive desorption of iodine. The acceleration of the reductive desorption of
      iodine suggests the existence of a weak interaction between the polymer layer and
      iodine. Not only the first polymer adlayers but also partially adsorbed secondary
      adlayers with "on-top" epitaxial behavior were frequently observed for all
      polymer systems. The alignment of the polymer chains in the adlayers possessed a
      certain regularity in terms of a regular interval between polymer chains because
      of repulsive interpolymer interactions.

PMID- 22954336
TI  - Deletion of angiotensin II type 1 receptor gene attenuates chronic alcohol
      induced retinal ganglion cell death with preservation of VEGF expression.
AB  - PURPOSE: To investigate how chronic alcohol consumption affects adult visual
      nervous system and whether renin-angiotensin system (RAS) is involved in this
      pathogenic process. METHODS: Male transgenic mice with angiotensin II (Ang II)
      type 1 (AT1) receptor gene knockout (AT1-KO) and age-matched wild-type (WT) mice
      were pair-fed a modified Lieber-DeCarli alcohol or isocaloric maltose dextrin
      control liquid diet for 2 months. At the end of the study, retinas were harvested
      and subjected to histopathological and immunohistochemical examination. RESULTS:
      We found that chronic alcohol consumption significantly increased retinal
      ganglion cell (RGC) apoptosis in the retina of WT mice, but not AT1-KO mice,
      detected by terminal deoxynucleotidyl-transferase-mediated dUTP-nick-end labeling
      staining and caspase 3 activation, along with an up-regulation of AT1 expression
      in RGC. At the same time, the phosphorylation of P53 in RGCs was significantly
      increased for both WT and AT1-KO mice exposed to alcohol, which could be
      significantly, although partially, prevented by AT1 gene deletion. We further
      examined the expression of vascular endothelial growth factor (VEGF) and CD31,
      and found that alcohol treatment significantly decreased the expression of VEGF
      and CD31 in RGCs of WT mice, but not AT1-KO mice. CONCLUSION: Taken together, our
      study demonstrates that the induction of RGC apoptosis by chronic alcohol
      exposure may be related to p53-activation and VEGF depression, all which are
      partially dependent of AT1 receptor activation.

PMID- 22954337
TI  - Identification of volatile markers for indoor fungal growth and chemotaxonomic
      classification of Aspergillus species.
AB  - Microbial volatile organic compounds (MVOCs) were collected in water-damaged
      buildings to evaluate their use as possible indicators of indoor fungal growth.
      Fungal species isolated from contaminated buildings were screened for MVOC
      production on malt extract agar by means of headspace solid-phase microextraction
      followed by gas chromatography-mass spectrometry (GC-MS) analysis. Some
      sesquiterpenes, specifically derived from fungal growth, were detected in the
      sampled environments and the corresponding fungal producers were identified.
      Statistical analysis of the detected MVOC profiles allowed the identification of
      species-specific MVOCs or MVOC patterns for Aspergillus versicolor group,
      Aspergillus ustus, and Eurotium amstelodami. In addition, Chaetomium spp. and
      Epicoccum spp. were clearly differentiated by their volatile production from a
      group of 76 fungal strains belonging to different genera. These results are
      useful in the chemotaxonomic discrimination of fungal species, in aid to the
      classical morphological and molecular identification techniques.

PMID- 22954338
TI  - Patulin and secondary metabolite production by marine-derived Penicillium
      strains.
AB  - Genus Penicillium represents an important fungal group regarding to its mycotoxin
      production. Secondary metabolomes of eight marine-derived strains belonging to
      subgenera Furcatum and Penicillium were investigated using dereplication by
      liquid chromatography (LC)-Diode Array Detector (DAD)-mass spectrometry (MS)/MS.
      Each strain was grown on six different culture media to enhance the number of
      observable metabolites. Thirty-two secondary metabolites were detected in crude
      extracts with twenty first observations for studied species. Patulin, a major
      mycotoxin, was classically detected in extracts of Penicillium expansum, and was
      also isolated from Penicillium antarcticum cultures, whose secondary metabolome
      is still to be done. These detections constituted the first descriptions of
      patulin in marine strains of Penicillium, highlighting the risk for shellfish and
      their consumers due to the presence of these fungi in shellfish farming areas.
      Patulin induced acute neurotoxicity on Diptera larvae, indicating the interest of
      this bioassay as an additional tool for detection of this major mycotoxin in
      crude extracts.

PMID- 22954339
TI  - Quantifying functional heterothallism in the pseudohomothallic ascomycete
      Neurospora tetrasperma.
AB  - Neurospora tetrasperma is a pseudohomothallic filamentous ascomycete that has
      evolved from heterothallic ancestors. Throughout its life cycle, it is
      predominantly heterokaryotic for mating type, and thereby self-fertile. However,
      studies of N. tetrasperma have revealed the occasional production of self-sterile
      asexual and sexual spores of a single-mating type, indicating that it can be
      functionally heterothallic. Here, we report the extensive sampling and isolation
      of natural, heterokaryotic, strains of N. tetrasperma from the United Kingdom
      (UK): 99 strains were collected from Surrey, England, and four from Edinburgh,
      Scotland. We verified by phylogenetic analyses that these strains belong to N.
      tetrasperma. We isolated cultures from single germinated asexual spores (conidia)
      from 17 of these newly sampled UK strains from Surrey, and 16 previously sampled
      strains of N. tetrasperma from New Zealand (NZ). Our results show that the N.
      tetrasperma strains from the UK population produced a significantly greater
      proportion of self-sterile, homokaryotic conidia than the NZ population: the
      proportion of homokaryotic conidia was 42.6 % (133/312 spores) and 15.3 %
      (59/386) from the UK and the NZ populations, respectively. Although homokaryons
      recovered from several strains show a bias for one of the mating types, the total
      ratio of mat A to mat a mating type in homokaryons (UK: 72/61, NZ 28/31) did not
      deviate significantly from the expected 1:1 ratio for either of these
      populations. These results indicate that different populations exhibit
      differences in their life cycle characteristics, and that a higher degree of
      outcrossing might be expected from the UK population. This study points to the
      importance of studying multiple strains and populations when investigating life
      history traits of an organism with a complex life cycle, as previously undetected
      differences between populations may be revealed.

PMID- 22954340
TI  - Homothallic sexual reproduction of Pustula helianthicola and germination of
      oospores.
AB  - Sunflower white blister rust has become an important disease in many countries
      with intensive cultivation of the important oil crop. The biology of the pathogen
      is still partly unclear, particular with respect to its sexual reproduction and
      primary mode of infection. Zoospores released from sporangia of Pustula
      helianthicola were isolated individually and used for the inoculation of
      sunflower in order to generate unithallic, genetically homogenous infections.
      Single zoospore inoculation of young seedlings resulted in mitotic sporulation
      within subepidermal blisters on cotyledons and true leaves after approximately 2
      weeks. Three weeks postinoculation, the infected plants started forming oospores,
      hence indicating homothallic sexual reproduction of the pathogen. The development
      of oogonia and antheridia was studied using light and fluorescence microscopy.
      Oospores were isolated from infected plant tissue and used for infection and
      germination studies. Microscopic observation of isolated oospores showed
      germination that formed sessile vesicle-like structures, germ sporangia or only
      germ tubes. The rate of germination reached approximately 40 %. Germination was
      not dependant on a resting phase after oospore formation. Oospores applied to the
      above ground parts of sunflower seedlings lead to infections within a similar
      time frame as was achieved with mitotic sporangia. The results underline the
      importance of oospores for primary infection at the beginning of the season and
      for long-distance dispersal of the pathogen with sunflower seeds contaminated by
      oospores.

PMID- 22954341
TI  - Population genetics of the wood-rotting basidiomycete Armillaria cepistipes in a
      fragmented forest landscape.
AB  - Armillaria cepistipes is a common wood-rotting basidiomycete fungus found in most
      forests in Central Europe. In Switzerland, the habitat of A. cepistipes is
      fragmented because of the presence of major geographical barriers, in particular
      the Alps, and past deforestation. We analysed the impact of habitat fragmentation
      on the current spatial genetic structure of the Swiss A. cepistipes population. A
      total of 167 isolates were sampled across an area of 41 000 km(2) and genotyped
      at seven microsatellite and four single nucleotide polymorphism (SNP) loci. All
      isolates belonged to different genotypes which, according to the Bayesian
      clustering algorithm implemented in Tess, originated from a single gene pool. Our
      analyses indicate that the overall A. cepistipes population shows little, but
      significant (F(ST)=0.02), genetic differentiation. Such a situation suggests gene
      flow is strong, possibly due to long-distance dispersal of airborne
      basidiospores. This hypothesis is supported by the fact that we could not detect
      a pattern of isolation by distance. Gene flow is partially restricted by the high
      mountain ranges of the Alps, as indicated by a signal of spatial autocorrelation
      detected among genotypes separated by less than about 80-130 km. In contrast,
      past deforestation seems to have no significant effect on the current spatial
      population structure of A. cepistipes. This might indicate the existence of a
      time lag between the current spatial genetic structure and the processes that
      have induced this specific structure.

PMID- 22954342
TI  - Factors shaping communities of pyrophilous macrofungi in microhabitats destroyed
      by illegal campfires.
AB  - Pyrophilous macrofungi (PM) are a narrowly specialised group appearing
      exclusively in plant communities recently destroyed by fire. Their significance
      has hitherto been studied only for vegetation destroyed over large areas, while
      in small areas of fire, i.e., microhabitats they are viewed as independent
      components of the community linked only to the substratum. In the present work,
      the following hypotheses were tested: (1) species structures of PM in
      microhabitats depend on the type of plant community, (2) PM form communities on a
      small scale which are similar in structure and function to analogous large scale
      communities. We studied 20 surfaces destroyed by illegal campfires in four
      natural plant communities: oak-hornbeam forest Tilio-Carpinetum (TC), lowland
      acidophilus beech forest Luzulo pilosae-Fagetum (LF), suboceanic pine forest
      Leucobryo-Pinetum (LP), and an initial-phase xerothermic grassland community on a
      transitional habitat (MH). TC and LF habitats were conspicuously more favourable
      for PM than LP and MH. In TC and LF fire leads to significant loss of mycorrhizae
      in the upper layer of leaf litter. This provides a development opportunity for
      ectomycorrhizal PM species which, having little competition, substitute for the
      destroyed fragments of mycorrhizal networks. In LP and MH fire over a small
      surface does not destroy more deeply located mycorrhizal associations. Another
      important factor for PM influencing the quality of environment is the fertility
      of soil: highest in TC, intermediate in LF and lowest in LP and MH. The results
      casts doubt on the concept that PM are only synusia linked to the substratum
      (burnt wood). PM growing in microhabitats constitute an important group of
      organisms which facilitate rapid regeneration of plant community fragments
      destroyed by fire.

PMID- 22954343
TI  - Expression and secretion of Aspergillus fumigatus proteases are regulated in
      response to different protein substrates.
AB  - The ubiquitous filamentous fungus Aspergillus fumigatus secretes a number of
      allergens with protease activity and has been linked to a variety of allergic
      conditions such as Severe Asthma with Fungal Sensitization (SAFS) and Allergic
      Bronchopulmonary Aspergillosis (ABPA). However, it is unclear which allergen
      proteases are being secreted during fungal invasion and whether the local
      biological environment regulates their expression. Understanding the dynamic
      expression of allergen proteases during growth of A. fumigatus may lead to
      further characterisation of the pathogenesis of these disorders as well as
      improved standardisation in the commercial production of these allergens.
      Secretion of proteases during germination and early growth of A. fumigatus was
      investigated in response to various complex protein sources (pig lung homogenate,
      mucin or casein). Protease inhibitor studies demonstrated that A. fumigatus
      (AF293 strain) secretes predominately serine proteases during growth in pig lung
      based medium and mainly metalloproteases during growth in casein based medium but
      suppressed protease secretion in unmodified Vogel's minimal medium and secreted
      both types in mucin based medium. Analysis of gene transcription and protein
      identification by mass spectrometry showed that the matrix metalloprotease,
      Mep/Asp f 5 and the serine protease, Alp1/Asp f 13, were upregulated and secreted
      during growth in pig lung medium, whereas Alp1 was predominately expressed and
      secreted in mucin based medium. In casein medium, the matrix metalloprotease,
      Lap1, was also upregulated and secreted in addition to Mep and Alp1. These
      findings suggest that A. fumigatus is able to detect different complex proteins
      available as substrates in its environment and regulate protease secretion
      accordingly. There is a requirement for the standardisation of A. fumigatus
      allergen extracts used both in clinical diagnosis of A. fumigatus allergy and in
      research studies.

PMID- 22954345
TI  - Robust multi-parameter single-platform quantification of myeloid and B-lymphoid
      CD34 progenitor cells in all clinical CD34 cell sources and in thawed PBSC.
AB  - As B-lymphoid progenitor cells do not give rise to in vitro colony formation and
      are unlikely to support myeloid engraftment, we validated a five-color extension
      of the single platform Stem Cell Enumeration (SCE) kit, to routinely quantify
      myeloid and B-lymphoid progenitor cells. Fresh samples (n > 20 each) of
      granulocyte colony stimulating factor mobilized blood (peripheral blood (PB)),
      cord blood (CB), bone marrow (BM), and apheresis products (APs) were stained in
      TruCOUNTTM tubes and the results were compared with those from the two-color
      CD45/CD34 reagent combination and the three-color SCE kit. To address
      repeatability, 10 samples from one AP were prepared by four technicians. Aliquots
      (n = 15) of four frozen AP were analyzed after thawing. Excellent correlations
      were observed between the three kits (R(2) > 0.99), for the quantification of
      white blood cells and total CD34. The extended kit showed considerable amounts of
      B-lymphoid progenitors in all CD34 sources (0-20% of all CD34 in PB, AP, and CB;
      3-90% in BM). Very similar results were obtained when the same sample was
      prepared by different technicians. After thawing of frozen AP, the recovery of
      viable cells varied depending on the freezing medium employed, but the results
      from the different quantification methods were identical. Most non-viable cells
      were clearly identified with 7 Aminoactinomycin D (7AAD) but an additional gate
      in the forward scatter/side scatter was necessary to address dead cells negative
      for 7AAD. The extended SCE kit allows rapid and exact quantification of viable B
      lymphoid and myeloid CD34(+) cells in all cell sources and in thawed stem cell
      harvests, and may thus improve the correlation between CD34 number and
      engraftment kinetics.

PMID- 22954344
TI  - PnPMA1, an atypical plasma membrane H(+)-ATPase, is required for zoospore
      development in Phytophthora parasitica.
AB  - Biflagellate zoospores are the major infective agents that initiate plant
      infection for most Phytophthora species. Once released from sporangia, zoospores
      swim and use a number of tactic responses to actively target host tissues.
      However, the molecular mechanisms controlling zoospore development and behaviour
      are largely unknown. Previous studies have shown that the PnPMA1 gene is highly
      expressed in zoospores and germinated cysts of Phytophthora parasitica and
      encodes an atypical plasma membrane H(+)-ATPase containing an insertion of ~155
      amino acid residues at the C terminus. Using topology determination we now show
      that the C-terminal insertion loop in the PnPMA1 protein is located in the
      extracellular space. To elucidate the biological function of PnPMA1, PnPMA1
      deficient transformants were generated by homology-dependent gene silencing and
      were confirmed by quantitative PCR of PnPMA1 transcripts and detection of
      associated small interfering RNAs (siRNAs). High levels of PnPMA1 silencing in P.
      parasitica resulted in production of nonflagellate and large aberrant zoospores,
      rapid transition from zoospores to cysts, and a decreased germination rate of
      cysts. These results indicate that PnPMA1 plays important roles in zoospore
      development.

PMID- 22954346
TI  - Antigenic differences between vaccine and circulating wild-type mumps viruses
      decreases neutralization capacity of vaccine-induced antibodies.
AB  - A recent resurgence of mumps in doubly vaccinated cohorts has been observed,
      identifying genotype G as the current predominant genotype. In this study, the
      neutralization efficacy of guinea pig sera immunized with three vaccine viruses:
      L-Zagreb, Urabe AM9 and JL5, was tested against seven mumps viruses: three
      vaccine strains and four wild-type strains (two of genotype G, one of genotype C,
      one of genotype D) isolated during 1998-2011. All sera neutralized all viruses
      although at different levels. The neutralization efficiency of sera decreases
      several fold by temporal order of virus isolation. Therefore, we concluded that
      gradual evolution of mumps viruses, rather than belonging to a certain genotype,
      results in an antigenic divergence from the vaccine strains that decrease the
      neutralization capacity of vaccine-induced antibodies. Moreover, the amino-acid
      sequence alignment revealed three new potentially relevant regions for escape
      from neutralization, i.e. 113-130, 375-403 and 440-443.

PMID- 22954348
TI  - Vitrification of immature bovine cumulus-oocyte complexes: effects of
      cryoprotectants, the vitrification procedure and warming time on cleavage and
      embryo development.
AB  - BACKGROUND: The present studies evaluated the effects of cryoprotectants, the
      vitrification procedure and time in the warming solution containing sucrose on
      cleavage and embryo development of immature (GV stage) bovine cumulus-oocyte
      complexes (COCs). METHODS: Two experiments were conducted. In Experiment 1, COCs
      (n = 420) were randomly assigned to four groups: 1) CONTROL GROUP: no treatment;
      2) VS1 group: COCs were exposed to vitrification solution 1 (VS1) containing 7.5%
      ethylene glycol [EG] + 7.5% dimethyl sulfoxide [DMSO] + 20% calf serum [CS] in
      TCM-199 at 37 C for 5 min; 3) VS1 + VS2 group: COCs were exposed to VS1 for 5 min
      followed by VS2 (15% EG + 15% DMSO + 17.1% sucrose + 20% CS) at 37 C for 45-60
      sec; and 4) Vitrified group: COCs were exposed to VS1 and VS2, loaded on
      cryotops, vitrified in liquid nitrogen and then warmed in TCM-199 + 17.1% sucrose
      + 20% CS at 37 C for 1 min. In Experiment 2, COCs (n = 581) were assigned to the
      same groups, but those in VS1, VS1 + VS2 and Vitrified groups were sub-divided
      and exposed to the warming solution for either 1 or 5 min. After treatment and/or
      warming, all COCs in both experiments underwent in vitro maturation, in vitro
      fertilization and in vitro culture. RESULTS: Cleavage and blastocyst rates did
      not differ among Control, VS1 and VS1 + VS2 groups in either experiment. In
      Experiment 2, there was no effect of time in the warming solution.However, both
      cleavage and blastocyst rates were lower (P < 0.001) in the Vitrified group than
      in the Control, VS1 and VS1 + VS2 groups (40.9 and 1.6% vs 92.2 and 34.4%, 79.4
      and 25.2%, and 80.2 and 20.8%, respectively in Experiment 1, and 25.0 and 1.7% vs
      75.3 and 27.2%, 67.9 and 19.5%, and 62.7 and 22.5%, respectively in Experiment
      2). CONCLUSIONS: The permeating cryoprotectants (EG and DMSO) present in VS1 and
      VS2 solutions and the time in the warming solution containing sucrose had no
      adverse effects on cleavage and blastocyst rates of immature bovine COCs.
      However, cleavage rate and early embryo development were reduced following the
      vitrification and warming.

PMID- 22954349
TI  - A drug safety evaluation of  everolimus  in kidney transplantation.
AB  - INTRODUCTION: Calcineurin inhibitors (CNI) have greatly reduced the rate of acute
      rejection and improved short-term graft survival after organ transplantation,
      however, long-term survival has hardly changed since their introduction. CNIs are
      believed to contribute to graft fibrosis, have side effects that adversely affect
      cardiovascular risk, and are associated with an increased rate of post-transplant
      malignancies. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, is
      not associated with graft fibrosis, has a superior cardiovascular risk profile to
      CNI therapy and has shown potential for the prevention and treatment of diverse
      forms of cancer. AREAS COVERED: This review summarizes key aspects of everolimus,
      including its mechanism of action, pharmacokinetics, pharmacodynamics, drug-drug
      interactions and pivotal clinical studies with a focus on safety and efficacy.
      EXPERT OPINION: Everolimus is effective in improving graft function in selected
      kidney transplant patients. Most adverse events are present for a short time
      after the introduction of everolimus, and are manageable. Everolimus has the
      potential to become an important agent in de novo and maintenance immunotherapy
      in kidney transplant recipients.

PMID- 22954350
TI  - Origins of stereoselectivities of dihydroxylations of cis-bicyclo[3.3.0]octenes.
AB  - Stereoselectivities of the dihydroxylations of cis-bicyclo[3.3.0]octene
      intermediates for a projected total synthesis of chromodorolide A have been
      explored experimentally. The reaction occurs unexpectedly on the apparently more
      hindered (concave) face; this result has been explained through computational
      studies using B3LYP and B3LYP-D3 methods. Torsional effects are largely
      responsible for the stereoselectivity encountered in the chromodorolide A
      synthesis. Many literature examples have been reported on related cases. QM
      calculations show that the stereoselectivities of dihydroxylations of fused
      cyclopentenes are influenced by the conformational rigidity or flexibility of the
      substrate. Torsional, electrostatic, and steric effects can all influence
      stereoselectivity, and the rigidity or flexibility of conformations of reactants
      provides a predictive guide to stereoselectivity.

PMID- 22954352
TI  - Peptide chemistry.

PMID- 22954351
TI  - Low tidal volume protects pulmonary vasomotor function from "second-hit" injury
      in acute lung injury rats.
AB  - BACKGROUND: Sepsis could induce indirect acute lung injury(ALI), and pulmonary
      vasomotor dysfunction. While low tidal volume is advocated for treatment of ALI
      patients. However, there is no evidence for low tidal volume that it could
      mitigate pulmonary vasomotor dysfunction in indirect ALI. Our study is to
      evaluate whether low tidal volume ventilation could protect the pulmonary
      vascular function in indirect lipopolysaccharide (LPS) induced acute lung injury
      rats. METHODS: An indirect ALI rat model was induced by intravenous infusion of
      LPS. Thirty rats (n = 6 in each group) were randomly divided into (1)Control
      group; (2) ALI group; (3) LV group (tidal volume of 6mL/kg); (4) MV group (tidal
      volume of 12mL/kg); (5)VLV group (tidal volume of 3mL/kg). Mean arterial pressure
      and blood gas analysis were monitored every 2 hours throughout the experiment.
      Lung tissues and pulmonary artery rings were immediately harvested after the rats
      were bled to be killed to detect the contents of endothelin-1 (ET-1), endothelial
      nitric oxide synthase (eNOS) and TNF-alpha. Acetylcholine (Ache)-induced
      endothelium-dependent and sodium nitroprusside (SNP)-induced endothelium
      independent relaxation of isolated pulmonary artery rings were measured by
      tensiometry. RESULTS: There was no difference within groups concerning blood
      pressure, PaCO2 and SNP-induced endothelium-independent relaxation of pulmonary
      artery rings. Compared with MV group, LV group significantly reduced LPS-induced
      expression of ET-1 level (113.79 +/- 7.33pg/mL vs. 152.52 +/- 12.75pg/mL, P <
      0.05) and TNF-alpha (3305.09 +/- 334.29pg/mL vs.4144.07 +/- 608.21pg/mL, P <
      0.05), increased the expression of eNOS (IOD: 15032.05 +/- 5925.07 vs. 11454.32
      +/- 6035.47, P < 0.05). While Ache (10-7mol/L-10-4mol/L)-induced vasodilatation
      was ameliorated 30% more in LV group than in MV group. CONCLUSIONS: Low tidal
      volume could protect the pulmonary vasodilative function during indirect ALI by
      decreasing vasoconstrictor factors, increasing expressions of vasodilator factors
      in pulmonary endothelial cells, and inhibiting inflammation injuries.

PMID- 22954353
TI  - Vasopressin in health and disease with a focus on affective disorders.
AB  - The therapies of mood and anxiety disorders are not solved, because current
      antidepressants have delayed onset of therapeutic action and a significant number
      of patients are non-responsive. Research on the field was leaning towards
      neuropeptides as therapeutic targets. Vasopressin (VP) is a hot candidate, as
      beyond its peripheral actions VP is implicated in interneuronal communication and
      modulates the hypothalamo-pituitary-adrenal (HPA), the key stress axis, as well
      as behavioural functions. Affective disorders are stress related disorders and
      the most frequently occurring abnormality in depressed subjects is hyperactivity
      of the HPA. VP with nucleus paraventricularis hypothalami origin is a direct
      adrenocorticotrophin secretagogue through its V1b receptor. VP seems to have
      special importance under prolonged stress conditions, which are known to be
      strong predictive factor of depressive disorder and can induce depressive-like
      symptoms. Preclinical and clinical data summarized in this review underline the
      importance of VP in the development of anxiety- and depressive-like symptoms.
      Orally active nonpeptiderg V1b antagonists were developed and seemed to have
      effective anxiolytic and antidepressant profile in preclinical studies, which was
      not fully confirmed by clinical observations. It seems that V1a receptors on
      special brain areas could have same importance. Taken together current knowledge
      strongly implies an importance of vasopressinergic regulation in affective
      disorders and consider VP as endogenous anxiogenic/depressogenic substance.
      However, wide range of side effects could develop as a result of an intervention
      on the VP system; therefore there is a need for area-specific targeting of VP
      receptors (e.g. with modified nanoparticles).

PMID- 22954354
TI  - A prospective study of the impact of musculoskeletal pain and radiographic
      osteoarthritis on health related quality of life in community dwelling older
      people.
AB  - BACKGROUND: Pain and radiographic changes are common in persons with
      osteoarthritis, but their relative contributions to quality of life are unknown.
      METHODS: Prospective cohort study of 1098 men and women aged 50-80 years,
      randomly selected from the electoral roll. Participants were interviewed at
      baseline and approximately 2.6 and five years later. Participants self-reported
      prior diagnosis of arthritis and presence of joint pain. Joint space narrowing
      (JSN) and osteophytes at the hip and knee were assessed by X-ray. Quality of life
      (QoL) was assessed using the Assessment of QoL (AQoL) instrument. Data was
      analysed using linear regression and mixed modelling. RESULTS: The median AQoL
      score at baseline was 7.0, indicating very good QoL. Prevalence of pain ranged
      from 38-62%. Over five years of observation, pain in the neck, shoulders, back,
      hips, hands, knees and feet were all independently and negatively associated with
      QoL, in a dose-response relationship. Diagnosed osteoarthritis at all sites was
      associated with poorer QoL but after adjustment for pain, this only remained
      significant at the back. Radiographic OA was not associated with QoL. While AQoL
      scores declined over five years, there was no evidence of an interaction between
      pain and time. CONCLUSIONS: Pain is common in older adults, is stable over time,
      and the strongest musculoskeletal correlate of QoL. It also mediates the
      association between diagnosed OA and QoL. Since the same factors were associated
      with quality of life over time as at baseline, this suggests that quality of life
      tracks over a five year period.

PMID- 22954355
TI  - Iridium-catalyzed regioselective and enantioselective allylation of
      trimethylsiloxyfuran.
AB  - We report the regio- and enantioselective allylation of an ester enolate,
      trimethylsiloxyfuran. This enolate reacts at the 3-position with linear aromatic
      allylic carbonates or aliphatic allylic benzoates to form the branched
      substitution products in the presence of a metallacyclic iridium catalyst. This
      process provides access to synthetically important 3-substituted butenolides in
      enantioenriched form. Stoichiometric reactions of the allyliridium intermediate
      suggest that the trimethylsiloxyfuran is activated by the carboxylate leaving
      group.

PMID- 22954356
TI  - A combined analysis of microarray gene expression studies of the human prefrontal
      cortex identifies genes implicated in schizophrenia.
AB  - Small cohort sizes and modest levels of gene expression changes in brain tissue
      have plagued the statistical approaches employed in microarray studies
      investigating the mechanism of schizophrenia. To combat these problems a combined
      analysis of six prior microarray studies was performed to facilitate the robust
      statistical analysis of gene expression data from the dorsolateral prefrontal
      cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate
      permutation tests identified 144 genes that were differentially expressed between
      schizophrenia and control groups. Seventy of these genes were identified as
      differentially expressed in at least one component microarray study but none of
      these individual studies had the power to identify the remaining 74 genes,
      demonstrating the utility of a combined approach. Gene ontology terms and
      biological pathways that were significantly enriched for differentially expressed
      genes were related to neuronal cell-cell signaling, mesenchymal induction, and
      mitogen-activated protein kinase signaling, which have all previously been
      associated with the etiopathogenesis of schizophrenia. The differential
      expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by
      real-time quantitative PCR in an independent cohort using postmortem human
      prefrontal cortex samples. Comparison of gene expression between schizophrenic
      subjects with and without detectable levels of antipsychotics in their blood
      suggests that the modulation of MT1X and S100A8 may be the result of drug
      exposure. In conclusion, this combined analysis has resulted in a statistically
      robust identification of genes whose dysregulation may contribute to the
      mechanism of schizophrenia.

PMID- 22954357
TI  - Structure-based design of highly selective beta-secretase inhibitors: synthesis,
      biological evaluation, and protein-ligand X-ray crystal structure.
AB  - The structure-based design, synthesis, and X-ray structure of protein-ligand
      complexes of exceptionally potent and selective beta-secretase inhibitors are
      described. The inhibitors are designed specifically to interact with S(1)' active
      site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5
      has exhibited exceedingly potent inhibitory activity (K(i) = 17 pM) and high
      selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein
      ligand crystal structure revealed important molecular insight into these
      selectivities. These interactions may serve as an important guide to design
      selectivity over the physiologically important aspartic acid proteases.

PMID- 22954358
TI  - Gas-phase synthesis of the silaisocyanoethylene molecule (C2H3NSi).
AB  - The gas-phase reaction between the silicon nitride radical (SiN) and the
      prototypical olefin--ethylene--is investigated experimentally and theoretically
      for the first time. Silicon nitride (SiN) and the cyano radical (CN) are
      isoelectronic; however, their chemical reactivities and structures are
      drastically different from each other. Through the use of the cross molecular
      beam technique, we were able to study the notoriously refractory silicon nitride
      radical in reaction with ethylene under single-collision conditions. We
      investigated the similarities and also the distinct differences with the cyano
      radical-ethylene system. We find that the silicon nitride radical bonds by the
      nitrogen atom to the double bond of ethylene; in comparison, the cyano radical
      adds via its carbon atom. The silicon nitride addition is barrierless, forming a
      long-lived SiNCH(2)CH(2) collision complex, which is also able to isomerize via a
      hydrogen shift to the SiNCHCH(3) intermediate. Both isomers can emit a hydrogen
      atom via tight transition states to form the silaisocyanoethylene (SiNC(2)H(3))
      molecule in an overall exoergic reaction. This presents the very first experiment
      in which the silaisocyanoethylene molecule--a member of the silaisocyanide family
      -has been formed via a directed synthesis under gas-phase single-collision
      conditions. In comparison with the isoelectronic cyano-ethylene system, the
      cyanoethylene (C(2)H(3)CN) isomer is formed. Therefore, the replacement of a
      single carbon atom by an isovalent silicon atom, i.e. shifting from the cyano
      (CN) to the silicon nitride (SiN) radical, has a dramatic influence not only on
      the reactivity with ethylene (carbon atom versus nitrogen atom addition) but also
      on the final reaction products. In the reactions of ethylene with silicon nitride
      and the cyano radical, the silaisonitrile over the silanitrile and the nitrile
      over the isonitrile reaction products are favored, respectively. This reaction
      provides rare experimental data for investigating the chemistry of bimolecular
      reactions of silicon nitride diatomics in chemical vapor deposition techniques
      and interstellar environments.

PMID- 22954359
TI  - DNA stickers promote polymer adsorption onto cellulose.
AB  - Adsorption of oligonucleotides onto model cellulose surfaces was investigated by
      comparing the Boese and Breaker's cellulose binding oligonucleotide (CBO) with a
      nonspecific oligonucleotide control (NSO). Measurements using the quartz crystal
      microbalance with dissipation technique confirmed that CBO adsorbed onto
      cellulose more than NSO, particularly at high ionic strengths (100 mM CaCl(2)).
      CBO showed a higher maximum adsorption on nanofibrillated and nanocrystalline
      cellulose than on regenerated cellulose, indicating a preference for the native
      cellulose I crystal structure under conditions that favored specific adsorption
      over calcium-mediated electrostatically driven adsorption. In addition, an
      anionic polyacrylamide (A-PAM) with grafted CBO also adsorbed onto the surface of
      cellulose in CaCl(2), whereas the unmodified A-PAM did not. This work shows that
      CBO performs as a "sticker", facilitating the adsorption of polyacrylamide onto
      cellulose, even under high ionic strength conditions where the adsorption of
      conventional polyelectrolytes is inhibited.

PMID- 22954360
TI  - Developmental and digestive flexibilities in the midgut of a polyphagous pest,
      the cotton bollworm, Helicoverpa armigera.
AB  - Developmental patterns and survival of the cotton bollworm, Helicoverpa armigera
      Hubner (Lepidoptera: Noctuidae), a polyphagous insect pest, have been studied
      with reference to the effect of diet on major gut digestive enzymes (amylases,
      proteases, and lipases). Significant correlations between nutritional quality of
      the diet and larval and pupal mass were observed when H. armigera larvae were fed
      on various host plants viz. legumes (chickpea and pigeonpea), vegetables (tomato
      and okra), flowers (rose and marigold), and cereals (sorghum and maize). Larvae
      fed on diets rich in proteins and/or carbohydrates (pigeonpea, chickpea, maize,
      and sorghum) showed higher larval mass and developed more rapidly than larvae fed
      on diets with low protein and carbohydrate content (rose, marigold, okra, and
      tomato). Low calorific value diets like rose and marigold resulted in higher
      mortality (25-35%) of H. armigera. Even with highly varying development
      efficiency and larval/pupal survival rates, H. armigera populations feeding on
      different diets completed their life cycles. Digestive enzymes of H. armigera
      displayed variable expression levels and were found to be regulated on the basis
      of macromolecular composition of the diet. Post-ingestive adaptations operating
      at the gut level, in the form of controlled release of digestive enzymes, might
      be a key factor contributing to the physiological plasticity in H. armigera.

PMID- 22954361
TI  - In vitro selection of highly efficient G-quadruplex-based DNAzymes.
AB  - Because of their ability to greatly enhance the low natural peroxidase activity
      of hemin, G-quadruplex-based DNAzymes have been widely used as an alternative to
      peroxidases for many colorimetric, chemiluminescent, or visual detections of
      metal ions, small molecules, nucleic acids, proteins, and cancer cells. To obtain
      G-quadruplex-based DNAzymes with better peroxidase activity, we designed three 81
      nt ssDNA libraries containing 25%, 35%, and 45% guanine bases, respectively, at
      the 45-nt random regions to evolve hemin-binding DNA aptamers using hemin-agarose
      beads by SELEX (systematic evolution of ligands by exponential enrichment). Some
      G-rich sequences were obtained after 6 rounds of selection and optimized for
      stronger binding affinity to hemin and higher peroxidase activity. Our results
      show that the truncated aptamer [B7]-3-0 folds into compact parallel G-quadruplex
      structure and exhibits the highest peroxidase activity and strong binding
      affinity to hemin with 29 +/- 4 nM of K(d). It was found that the core G-motifs
      sequences with 5'-flanking nucleotides exhibit higher peroxidase activity than
      those with 3'-flanking nucleotides. The numbers of 5'-flanking nucleotides also
      influence peroxidase activity. In addition, 2'-O-methyl modification facilitates
      the self-assembly of parallel G-quadruplex [B7]-3-0 and significantly promotes
      peroxidase activity. This study identifies a G-quadruplex sequence with
      peroxidase-like activity higher than any other sequences reported so far, which
      could be potentially used to improve the analytical performance of a wide variety
      of peroxidase-based bioassays.

PMID- 22954362
TI  - A zeolite-like zinc triazolate framework with high gas adsorption and separation
      performance.
AB  - The reaction of commercially available 3-amino-1,2,4-triazole (Hatz) and
      Zn(OH)(2) at room temperature produced a porous zeolite-like metal azolate
      framework, [Zn(atz)(2)] (MAF-66). Single-crystal X-ray diffraction studies of MAF
      66 showed that atz(-) served as an imidazolate-type ligand, linking tetrahedral
      Zn(II) ions to form a noninterpenetrated dia framework, which contains a narrow,
      three-dimensional intersecting channel system (void = 49.8%) functionalized by
      amino groups and uncoordinated triazolate N atoms on the pore surface. Gas
      sorption measurements of MAF-66 revealed high CO(2) uptakes (27.6/19.4 wt % at
      273/298 K and 1 atm) and high Henry's law CO(2)/N(2) selectivity (403/225 at
      273/298 K). The host-guest interactions between CO(2) and the pore surface were
      also studied by in situ IR absorption spectroscopy and powder X-ray diffraction
      measurements.

PMID- 22954363
TI  - Reputations: a critical yet neglected area of scholarly enquiry.

PMID- 22954364
TI  - How children with normal hearing and children with a cochlear implant use
      mentalizing vocabulary and other evaluative expressions in their narratives.
AB  - This study explored the use of mental state and emotion terms and other
      evaluative expressions in the story generation of 65 children (aged 2-8 years)
      with normal hearing (NH) and 11 children (aged 3-7 years) using a cochlear
      implant (CI). Children generated stories on the basis of sets of sequential
      pictures. The stories of the children with CI were obtained over the 5-year
      follow-up period. The children with NH continued to show an increased story
      length (number of words) with age. In the children with a CI, the increase was
      similar initially, but plateaued after 3 years of using a CI. In children with
      NH, the spontaneous use of mental state vocabulary in narratives increased
      significantly between the ages of three and six. The delayed use of mental state
      terms in the children with a CI was related to a reduced amount of linguistic
      production overall. The theoretical and clinical implications were discussed.

PMID- 22954365
TI  - An examination of fast mapping skills in preschool children from families with
      low socioeconomic status.
AB  - Researchers consistently report that children from low socioeconomic status (SES)
      families have, on average, smaller vocabularies as assessed by measures of
      existing vocabulary knowledge than children from higher SES families. Yet, few
      studies have examined the word-learning process of children from low SES
      families. The present study was an examination of fast mapping by preschoolers
      from low SES families. The study also examined the relation between measures of
      existing vocabulary and performance on the fast mapping task. Forty-six
      preschoolers (mean age: 4;6, range: 3;11-5;3) from low SES families completed a
      part-term fast mapping task and two measures of existing vocabulary knowledge. On
      the fast mapping task, children demonstrated the use of three sources of
      information (familiar whole objects, possessive syntax and whole-part
      juxtaposition). Measures of existing vocabulary did not correlate with
      performance on the fast mapping task. Findings suggest that children from low SES
      families use multiple sources of information in linguistic input to learn words.

PMID- 22954366
TI  - Quantitative analysis of language production in Parkinson's disease using a cued
      sentence generation task.
AB  - The present study examined language production skills in Parkinson's disease (PD)
      patients. A unique cued sentence generation task was created in order to reduce
      demands on memory and attention. Differences in sentence production abilities
      according to disease severity and cognitive impairments were assessed. Language
      samples were obtained from 20 PD patients and 20 healthy control participants
      matched for age, sex and educational level. In addition, a cognitive test for
      verbal memory and resistance to cognitive interference was administered.
      Statistical comparisons revealed significant language changes in an advanced
      stage of the disease. Advanced PD patients showed a reduction in lexical
      diversity in notional verbs, which was absent in nouns. Cognitive dysfunctions
      such as impaired verbal memory are suggested to contribute to the typical
      noun/verb dissociation in PD patients. In addition, advanced PD patients produced
      more semantic perseverations, which may be related to set-switching problems. In
      conclusion, whether language disturbances in PD are the result of non-linguistic
      cognitive dysfunctions or reflect pure language deficits exacerbated by cognitive
      impairments, remains a matter of debate. However, the negative impact of
      cognitive dysfunctions may be important.

PMID- 22954367
TI  - Idiosyncratic gesture use in atypical language development, and its interaction
      with speech rhythm, word juncture, syntax, pragmatics and discourse: a case
      study.
AB  - Very little is known about the use of gesture by children with developmental
      language disorders (DLDs). This case study of 'Lucy', a child aged 4;10 with a
      DLD, expands on what is known and in particular focuses on a type of
      idiosyncratic "rhythmic gesture" (RG) not previously reported. A fine-grained
      qualitative analysis was carried out of video recordings of Lucy in conversation
      with the first author. This revealed that Lucy's RG was closely integrated in
      complex ways with her use of other gesture types, speech rhythm, word juncture,
      syntax, pragmatics, discourse, visual processing and processing demands
      generally. Indeed, the only satisfactory way to explain it was as a partial
      byproduct of such interactions. These findings support the theoretical accounts
      of gesture which see it as just one component of a multimodal, integrated
      signalling system (e.g. Goldin-Meadow, S. (2000). Beyond words: The importance of
      gesture to researchers and learners. Child Development, 71(1), 231-239), and
      emergentist accounts of communication impairment which regard compensatory
      adaptation as integral (e.g. Perkins, M. R. (2007). Pragmatic Impairment.
      Cambridge: Cambridge University Press.).

PMID- 22954368
TI  - Aggregation behaviors of PEO-PPO-ph-PPO-PEO and PPO-PEO-ph-PEO-PPO at an
      air/water interface: experimental study and molecular dynamics simulation.
AB  - The block polyethers PEO-PPO-ph-PPO-PEO (BPE) and PPO-PEO-ph-PEO-PPO (BEP) are
      synthesized by anionic polymerization using bisphenol A as initiator. Compared
      with Pluronic P123, the aggregation behaviors of BPE and BEP at an air/water
      interface are investigated by the surface tension and dilational viscoelasticity.
      The molecular construction can influence the efficiency and effectiveness of
      block polyethers in decreasing surface tension. BPE has the most efficient
      ability to decrease surface tension of water among the three block polyethers.
      The maximum surface excess concentration (Gamma(max)) of BPE is larger than that
      of BEP or P123. Moreover, the dilational modulus of BPE is almost the same as
      that of P123, but much larger than that of BEP. The molecular dynamics simulation
      provides the conformational variations of block polyethers at the air/water
      interface.

PMID- 22954369
TI  - Intracellular chemical gradients: morphing principle in bacteria.
AB  - Advances in computational biology allow systematic investigations to ascertain
      whether internal chemical gradients can be maintained in bacteria - an open
      question at the resolution limit of fluorescence microscopy. While it was
      previously believed that the small bacterial cell size and fast diffusion in the
      cytoplasm effectively remove any such gradient, a new computational study
      published in BMC Biophysics supports the emerging view that gradients can exist.
      The study arose from the recent observation that phosphorylated CtrA forms a
      gradient prior to cell division in Caulobacter crescentus, a bacterium known for
      its complicated cell cycle. Tropini et al. (2012) postulate that such gradients
      can provide an internal chemical compass, directing protein localization, cell
      division and cell development. More specifically, they describe biochemical and
      physical constraints on the formation of such gradients and explore a number of
      existing bacterial cell morphologies. These chemical gradients may limit in vitro
      analyses, and may ensure timing control and robustness to fluctuations during
      critical stages in cell development.

PMID- 22954370
TI  - Temporal modeling of highway crash counts for senior and non-senior drivers.
AB  - This paper introduces dynamic time series modeling in a Bayesian framework to
      uncover temporal patterns in highway crashes in Connecticut. Existing state
      sources provide data describing the time for each crash and demographic
      attributes of persons involved over the time period from January 1995 to December
      2009 as well as the traffic volumes and the characteristics of the roads on which
      these crashes occurred. Induced exposure techniques are used to estimate the
      exposure for senior and non-senior drivers by road access type (limited access
      and surface roads) and area type (urban or rural). We show that these dynamic
      models fit the data better than the usual GLM framework while also permitting
      discovery of temporal trends in the estimation of parameters, and that
      computational difficulties arising from Markov Chain Monte Carlo (MCMC)
      techniques can be handled by the innovative Integrated Nested Laplace
      Approximations (INLA). Using these techniques we find that while overall safety
      is increasing over time, the level of safety for senior drivers has remained more
      stagnant than for non-senior drivers, particularly on rural limited access roads.
      The greatest opportunity for improvement of safety for senior drivers is on rural
      surface roads.

PMID- 22954371
TI  - Sample size estimation to substantiate freedom from disease for clustered binary
      data with a specific risk profile.
AB  - Disease cases are often clustered within herds or generally groups that share
      common characteristics. Sample size formulae must adjust for the within-cluster
      correlation of the primary sampling units. Traditionally, the intra-cluster
      correlation coefficient (ICC), which is an average measure of the data
      heterogeneity, has been used to modify formulae for individual sample size
      estimation. However, subgroups of animals sharing common characteristics, may
      exhibit excessively less or more heterogeneity. Hence, sample size estimates
      based on the ICC may not achieve the desired precision and power when applied to
      these groups. We propose the use of the variance partition coefficient (VPC),
      which measures the clustering of infection/disease for individuals with a common
      risk profile. Sample size estimates are obtained separately for those groups that
      exhibit markedly different heterogeneity, thus, optimizing resource allocation. A
      VPC-based predictive simulation method for sample size estimation to substantiate
      freedom from disease is presented. To illustrate the benefits of the proposed
      approach we give two examples with the analysis of data from a risk factor study
      on Mycobacterium avium subsp. paratuberculosis infection, in Danish dairy cattle
      and a study on critical control points for Salmonella cross-contamination of
      pork, in Greek slaughterhouses.

PMID- 22954372
TI  - Amount and focus of physical therapy and occupational therapy for young children
      with cerebral palsy.
AB  - The aims of this study were to describe physical therapy (PT) and occupational
      therapy (OT) services for a cohort of 399 children with cerebral palsy (CP), 2-6
      years old, residing in the United States and Canada. Parents completed a services
      questionnaire by telephone interview. Therapists classified children's Gross
      Motor Function Classification System (GMFCS) level. Mean minutes per month of PT
      and OT were greater for children receiving services in both an educational and
      clinic setting. Mean minutes per month of PT and OT were greater for children in
      levels IV-V than children in level I and greater for children in the United
      States than children in Canada. Parents reported that interventions focused a
      moderate to great extent on primary impairments, secondary impairments, activity,
      and structured play activities, a moderate extent on environmental modifications
      and equipment; and a moderate to small extent on self-care routines. The results
      support the importance of coordination of PT and OT services.

PMID- 22954373
TI  - Tuning oxygen reduction reaction activity via controllable dealloying: a model
      study of ordered Cu3Pt/C intermetallic nanocatalysts.
AB  - A promising electrocatalyst prototype of low Pt mole fraction, intermetallic
      nanoparticles of Cu(3)Pt, has been prepared using a simple impregnation-reduction
      method, followed by a post heat-treatment. Two dealloying methods
      (electrochemical and chemical) were implemented to control the atomic-level
      morphology and improve performance for the oxygen reduction reaction (ORR). The
      morphology and elemental composition of the dealloyed nanoparticles were
      characterized at angstrom resolution using an aberration-corrected scanning
      transmission electron microscope equipped with an electron energy loss
      spectrometer. We found that the electrochemical dealloying method led to the
      formation of a thin Pt skin of ca. 1 nm in thickness with an ordered Cu(3)Pt core
      structure, while chemical leaching gave rise to a "spongy" structure with no
      ordered structure being preserved. A three-dimensional tomographic reconstruction
      indicated that numerous voids were formed in the chemically dealloyed
      nanoparticles. Both dealloying methods yielded enhanced specific and mass
      activities toward the ORR and higher stability relative to Pt/C. The spongy
      nanoparticles exhibited better mass activity with a slightly lower specific
      activity than the electrochemically dealloyed nanoparticles after 50 potential
      cycles. In both cases, the mass activity was still enhanced after 5000 potential
      cycles.

PMID- 22954377
TI  - Where's the charge? Protonation sites in gaseous ions change with hydration.
AB  - The role of water in stabilizing sites of protonation in small gaseous ions is
      investigated using electrospray ionization (ESI) coupled with infrared
      photodissociation spectroscopy and computational chemistry. Protonation of p
      aminobenzoic acid (PABA) and p-aminobenzoic acid methyl ester (PABAOMe) occurs at
      the carbonyl oxygen atom both in isolation and when one water molecule is
      attached. However, protonation occurs at the amine nitrogen atom, which is the
      most favorable site in aqueous solution, for PABAOMeH(+).(H(2)O)(3) and for a
      significant fraction of PABAH(+).(H(2)O)(6). Fewer water molecules are necessary
      to stabilize the solution-phase isomer of PABAOMeH(+) (3) than for PABAH(+)
      (>=6), indicating that the favorable hydrogen bonding in PABAH(+) is a more
      important factor than the higher gas-phase basicity of PABAOMeH(+) in stabilizing
      protonation at the carbonyl oxygen atom. Relative Gibbs free energies (133 K)
      calculated using B3LYP and MP2 with the 6-311++G** basis set were significantly
      different from each other, and both are in poor agreement with results from the
      experiments. omegaB97X-D/6-311++G**, which includes empirical dispersion
      corrections, gave results that were most consistent with the experimental data.
      The relative stabilities of protonating at the carbonyl oxygen atom for
      PABAH(+).(H(2)O)(0-6) and PABAOMeH(+).(H(2)O)(0-2) can be rationalized by
      resonance delocalization. These findings provide valuable insights into the
      solvent interactions that stabilize the location of a charge site and the
      structural transitions that can occur during the ESI desolvation process.

PMID- 22954375
TI  - Molecular phylogeny of the bivalve superfamily Galeommatoidea (Heterodonta,
      Veneroida) reveals dynamic evolution of symbiotic lifestyle and interphylum host
      switching.
AB  - BACKGROUND: Galeommatoidea is a superfamily of bivalves that exhibits remarkably
      diverse lifestyles. Many members of this group live attached to the body surface
      or inside the burrows of other marine invertebrates, including crustaceans,
      holothurians, echinoids, cnidarians, sipunculans and echiurans. These symbiotic
      species exhibit high host specificity, commensal interactions with hosts, and
      extreme morphological and behavioral adaptations to symbiotic life. Host
      specialization to various animal groups has likely played an important role in
      the evolution and diversification of this bivalve group. However, the
      evolutionary pathway that led to their ecological diversity is not well
      understood, in part because of their reduced and/or highly modified morphologies
      that have confounded traditional taxonomy. This study elucidates the taxonomy of
      the Galeommatoidea and their evolutionary history of symbiotic lifestyle based on
      a molecular phylogenic analysis of 33 galeommatoidean and five putative
      galeommatoidean species belonging to 27 genera and three families using two
      nuclear ribosomal genes (18S and 28S ribosomal DNA) and a nuclear (histone H3)
      and mitochondrial (cytochrome oxidase subunit I) protein-coding genes. RESULTS:
      Molecular phylogeny recovered six well-supported major clades within
      Galeommatoidea. Symbiotic species were found in all major clades, whereas free
      living species were grouped into two major clades. Species symbiotic with
      crustaceans, holothurians, sipunculans, and echiurans were each found in multiple
      major clades, suggesting that host specialization to these animal groups occurred
      repeatedly in Galeommatoidea. CONCLUSIONS: Our results suggest that the
      evolutionary history of host association in Galeommatoidea has been remarkably
      dynamic, involving frequent host switches between different animal phyla. Such an
      unusual pattern of dynamic host switching is considered to have resulted from
      their commensalistic lifestyle, in which they maintain filter-feeding habits even
      in symbiotic habitats. The results of the molecular phylogenetic analysis did not
      correspond with the current taxonomic circumscription. Galeommatidae and
      Lasaeidae were polyphyletic, and Basterotia, which is traditionally assigned to
      Cyamioidea, formed a monophyletic clade within Galeommatoidea.

PMID- 22954379
TI  - Visible light switching of a BF2-coordinated azo compound.
AB  - Here we report the synthesis and characterization of a BF(2)-azo complex that can
      be induced to isomerize without the need of deleterious UV light. The
      complexation of the azo group with BF(2), coupled with the extended conjugation
      of the N?N pi-electrons, increases the energy of the n-pi* transitions and
      introduces new pi-nonbonding (pi(nb)) to pi* transitions that dominate the
      visible region. The well separated pi(nb)-pi* transitions of the trans and cis
      isomers enable the efficient switching of the system by using only visible light.
      The complexation also leads to a slow cis -> trans thermal relaxation rate
      (t(1/2) = 12.5 h). Theoretical calculations indicate that the absorption bands in
      the visible range can be tuned using different Lewis acids, opening the way to a
      conceptually new strategy for the manipulation of azo compounds using only
      visible light.

PMID- 22954378
TI  - Safety and efficacy of immunomodulators and biologics during pregnancy and
      lactation for the treatment of inflammatory bowel disease.
AB  - INTRODUCTION: The inflammatory bowel diseases (IBD) are chronic, idiopathic,
      inflammatory conditions of the gastrointestinal tract, that peak in incidence
      during the reproductive years. Therefore, the safety of IBD medications during
      pregnancy and lactation is of significant interest to patients. Unfortunately,
      the current pregnancy labeling used by the United States Food and Drug
      Association (FDA) is often misinterpreted and may mislead healthcare providers
      and their patients to believe that risk increases from Category A to B to C to D
      to X, which in fact, is not the case. In addition, the FDA categories do not
      always distinguish between risks based on human versus animal data, or between
      differences in frequency, severity, and type of fetal developmental toxicities.
      AREAS COVERED: This article provides an in-depth review of the available safety
      data during pregnancy and lactation for the more potent immunosuppressants used
      to treat IBD: the immunomodulators and biologics. It also includes the authors'
      expert opinions on the use of these medications during these critical periods.
      EXPERT OPINION: The benefit-to-risk ratio for most immunomodulators and biologics
      used in the treatment of IBD favors medication continuation during pregnancy.
      Certain immunomodulators, however, can cause extreme fetal harm and should be
      used with caution. While human safety data regarding teratogenesis and some data
      on pregnancy outcomes exist for most IBD medications, long-term follow-up studies
      of children and young adults exposed to these drugs in utero are lacking. These
      studies are needed to determine if these drugs are of sufficiently low risk to be
      considered safe.

PMID- 22954380
TI  - Excited state intramolecular proton transfer (ESIPT) from phenol to carbon in
      selected phenylnaphthols and naphthylphenols.
AB  - ESIPT and solvent-assisted ESPT in isomeric phenyl naphthols and naphthyl phenols
      5-8 were investigated by preparative photolyses in CH3CN-D2O, fluorescence
      spectroscopy, LFP, and ab initio calculations. ESIPT takes place only in 5 (D
      exchange Phi = 0.3), whereas 6-8 undergo solvent-assisted PT with much lower
      efficiencies. The efficiency of the ESIPT and solvent-assisted PT is mainly
      determined by different populations of the reactive conformers in the ground
      state and the NEER principle. The D-exchange experiments and calculations using
      RI-CC2/cc-pVDZ show that 5 in S1 deactivates by direct ESIPT from the OH to the
      naphthalene position 1 through a conical intersection with S0, delivering QM 14
      that was detected by LFP (tau = 26 +/- 3 ns). ESIPT to position 3 in 5 is
      possible but it proceeds from a less-populated conformer and involves an energy
      barrier on S1. In solvent-assisted PT to naphthalene position 4 in 5, zwitterion
      17 is formed, which cyclizes to stable naphthofuran photoproducts 9-12. The
      regiochemistry of the deuteration in solvent-assisted PT was correlated with the
      NBO charges of the corresponding phenolates/naphtholates 5(-)-8(-). Combined
      experimental and theoretical data indicate that solvent-assisted PT takes place
      via a sequential mechanism involving first deprotonation of the phenol/naphthol,
      followed by the protonation by H2O in the S1 state of phenolate/naphtholate. The
      site of protonation by H2O is mostly at the naphthalene alpha-position.

PMID- 22954381
TI  - Biomimetic alignment of zinc oxide nanoparticles along a peptide nanofiber.
AB  - Zinc oxide (ZnO) has potential applications in solar cells, chemical sensors, and
      piezoelectronic and optoelectronic devices due to its attractive physical and
      chemical properties. Recently, a solution-phase method has been used to
      synthesize ZnO crystals with diverse (from simple to hierarchical) nanostructures
      that is simple, of low cost, and scalable. This method requires template
      molecules to control the morphology of the ZnO crystals. In this paper, we
      describe the design and synthesis of two short peptides (RU-003,Ac-AIEKAXEIA
      NH(2); RU-027, EAHVMHKVAPRPGGGAIEKAXEIA-NH(2); X = l-2-naphthylalanine) and the
      characterization of their self-assembled nanostructures. We also report their
      potential for ZnO mineralization and the alignment of ZnO nanoparticles along
      peptide nanostructures at room temperature. Interestingly, nonapeptide RU-003
      predominantly formed a straight fibrous structure and induced the nucleation of
      ZnO at its surface, leading to an alignment of ZnO nanoparticles along a peptide
      nanofiber. This novel method holds promise for the room-temperature fabrication
      of ZnO catalysts with increased specific surface area, ZnO-gated transistors, and
      ZnO-based nanomaterials for optical applications.

PMID- 22954382
TI  - Role of substrate in directing the self-assembly of multicomponent supramolecular
      networks at the liquid-solid interface.
AB  - The self-assembly of multicomponent networks at the liquid-solid interface
      between Au(111) or highly oriented pyrolytic graphite (HOPG) and organic solvents
      was investigated using scanning tunneling microscopy. Alkoxylated
      dehydrobenzo[12]annulene (DBA) derivatives form hexagonal nanoporous networks,
      which trap either single molecules of coronene (COR) or small clusters of COR and
      isophthalic acid to form multicomponent networks. The pattern of interdigitation
      between alkyl chains from DBA molecules produces hexagonal pores that are either
      chiral or achiral. On Au(111) substrates multicomponent networks display an
      ordered superlattice arrangement of chiral and achiral pores. In comparison,
      similar networks on HOPG display only chiral pores. The unique superlattice
      structure observed on Au(111) is related to a lower energetic preference for
      chiral pores than on HOPG and increased diffusion barriers for guest molecules.
      The increased diffusion barriers for guests allow them to act as nucleation sites
      for the formation of achiral pores. Following the initial nucleation of an
      achiral pore, restrictions imposed by the accommodation of guests within the
      porous network mean that subsequent growth naturally leads to the formation of
      the superlattice structure.

PMID- 22954383
TI  - Appropriate use of indwelling urethra catheters in hospitalized patients: results
      of a multicentre prevalence study.
AB  - BACKGROUND: Although indwelling urethra catheterization is a medical intervention
      with well-defined risks, studies show that approximately 14-38% of the indwelling
      urethra catheters (IUCs) are placed without a specific medical indication. In
      this paper we describe the prevalence of IUCs, including their inappropriate use
      in the Netherlands. We also determine factors associated with inappropriate use
      of IUCs in hospitalized patients. METHODS: In 28 Dutch hospitals, prevalence
      surveys were performed biannually in 2009 and 2010 within the PREZIES-network.
      All patients admitted to a participating hospital and who had an IUC in place at
      the day of the survey were included. Pre-determined criteria were used to
      categorize the indication for catheterization as appropriate or inappropriate.
      RESULTS: A total of 14,252 patients was included and 3020 (21.2%) of them had an
      IUC (range hospitals 13.4-27.3). Initial catheter placement was inappropriate in
      5.2% of patients and 7.5% patients had an inappropriate indication at the day of
      the survey. In multivariate analyses inappropriate catheter use at the time of
      placement was associated with female sex, older age, admission on a non-intensive
      care ward, and not having had surgery. Inappropriate catheter use at the time of
      survey showed comparable associated factors. CONCLUSIONS: Although lower than in
      many other countries, inappropriate use of IUC is present in Dutch hospitals. To
      reduce the inappropriate use of IUCs, recommended components of care (bundle for
      UTI), including daily revision and registration of the indication for
      catheterization, should be introduced for all patients with an IUC. Additionally,
      an education and awareness campaign about appropriate indications for IUC should
      be available.

PMID- 22954384
TI  - A large-scale newborn hearing screening in rural areas in China.
AB  - OBJECTIVES: Newborn hearing screening has been successfully implemented in cities
      of China, but not in rural areas. This study aimed to provide guidance on
      implementing hearing screening in the rural areas of China. METHODS: Subjects
      were 11,568 babies who were born in 5 counties of Hubei Province of China.
      Hearing screening followed a two-stage strategy with transient evoked otoacoustic
      emissions (TEOAEs). Infants referred after the second-stage screening were tested
      by diagnostic auditory brainstem response (ABR). RESULTS: The subjects screened
      included 10,665 (92.2%) normal newborns and 903 (7.8%) newborns with high-risk of
      hearing loss. While 8190 (70.8%) newborns passed the initial screening, 135
      newborns failed in the re-screening, and 90 (66.7%) of these 135 newborns
      received diagnostic assessment. Finally, 58 infants were diagnosed as hearing
      loss, and the prevalence of congenital hearing loss among newborns in rural areas
      was 0.5% (58/11,568). CONCLUSIONS: This large-scale newborn hearing screening in
      rural areas of Hubei Province of China demonstrated that the screening rate and
      referral rate for high-risk infants are low. Urgent measures should be taken by
      the government to promote newborn hearing screening in the rural areas.

PMID- 22954385
TI  - Bicomponent lignocellulose thin films to study the role of surface lignin in
      cellulolytic reactions.
AB  - Ultrathin bicomponent films of cellulose and lignin derivatives were deposited on
      silica supports by spin coating, and after conversion into the respective polymer
      precursor, they were used as a model system to investigate interfacial phenomena
      relevant to lignocellulose biocatalysis. Film morphology, surface chemical
      composition, and wettability were determined by atomic force microscopy, X-ray
      photoelectron spectroscopy, and water contact angle, respectively. Phase
      separation of cellulose and lignin produced structures that resembled the cell
      wall of fibers and were used to monitor enzyme binding and cellulolytic reactions
      via quartz crystal microgravimetry. The rate and extent of hydrolysis was
      quantified by using kinetic models that indicated the role of the surface lignin
      domains in enzyme inhibition. Hydrophobic interactions between cellulases and the
      substrates and their critical role on irreversible adsorption were elucidated by
      using acetylated lignin films with different degrees of substitution. Overall, it
      is concluded that sensors based on the proposed ultrathin films of lignocellulose
      can facilitate a better understanding of the complex events that occur during
      bioconversion of cellulosic biomass.

PMID- 22954386
TI  - Does availability of physical activity and food outlets differ by race and
      income? Findings from an enumeration study in a health disparate region.
AB  - BACKGROUND: Low-income, ethnic/racial minorities and rural populations are at
      increased risk for obesity and related chronic health conditions when compared to
      white, urban and higher-socio-economic status (SES) peers. Recent systematic
      reviews highlight the influence of the built environment on obesity, yet very few
      of these studies consider rural areas or populations. Utilizing a CBPR process,
      this study advances community-driven causal models to address obesity by
      exploring the difference in resources for physical activity and food outlets by
      block group race and income in a small regional city that anchors a rural health
      disparate region. To guide this inquiry we hypothesized that lower income and
      racially diverse block groups would have fewer food outlets, including fewer
      grocery stores and fewer physical activity outlets. We further hypothesized that
      walkability, as defined by a computed walkability index, would be lower in the
      lower income block groups. METHODS: Using census data and GIS, base maps of the
      region were created and block groups categorized by income and race. All food
      outlets and physical activity resources were enumerated and geocoded and a
      walkability index computed. Analyses included one-way MANOVA and spatial
      autocorrelation. RESULTS: In total, 49 stores, 160 restaurants and 79 physical
      activity outlets were enumerated. There were no differences in the number of
      outlets by block group income or race. Further, spatial analyses suggest that the
      distribution of outlets is dispersed across all block groups. CONCLUSIONS: Under
      the larger CPBR process, this enumeration study advances the causal models set
      forth by the community members to address obesity by providing an overview of the
      food and physical activity environment in this region. This data reflects the
      food and physical activity resources available to residents in the region and
      will aid many of the community-academic partners as they pursue intervention
      strategies targeting obesity.

PMID- 22954388
TI  - Alternative diets for Chrysomya putoria, an Old World screwworm fly.
AB  - Abstract   The purpose of this study was to evaluate the post-embryonic
      development of Chrysomya putoria (Wiedemann 1818) (Diptera: Calliphoridae) reared
      on a diet of gizzard or gizzard/agar homogenate, with a diet of beef used as the
      control. Four replicates per treatment were performed (60 mL of each diet). The
      gizzard (60%), distilled water, and agar homogenate were combined in a blender.
      Each replicate consisted of 40 newly hatched larvae of C. putoria (5(th)
      generation). Each glass beaker containing a diet was inserted into a larger flask
      containing sawdust, which was covered with a nylon cloth held in place by an
      elastic band. The larvae were weighed and stored in test tubes sealed with a
      nylon cloth and an elastic band. The average temperature, measured with a
      thermohygrograph, was 20.6  degrees C, and the average relative humidity was
      67.7%. The variation in the mean weight of mature larvae and in the duration of
      the larval, pupal, and total stages (newly hatched larvae to imagoes) were
      analyzed by Student's t-test (alpha = 5%), while viability was compared by ANOVA.
      The sex ratio was evaluated by the chi-squared test. The average duration of the
      period from the larval to imago stage was 8.868 days on the beef diet, 8.676 on
      the gizzard diet, and 9.067 on the gizzard/agar homogenate diet. Larval survival
      rates on these diets were 98, 92, and 73%, respectively, while pupal viabilities
      were 98, 91, and 71%, respectively, and larva-to-imago viabilities were 93, 83,
      and 64%, respectively. The duration of the pupal period differed significantly
      between the blowflies reared on the beef and gizzard/agar homogenate diets. The
      two diets proved to be good alternatives for rearing C. putoria.

PMID- 22954387
TI  - Small molecule inhibitors of Bacillus anthracis protective antigen proteolytic
      activation and oligomerization.
AB  - Protective antigen (PA), lethal factor, and edema factor, the protein toxins of
      Bacillus anthracis , are among its most important virulence factors and play a
      key role in infection. We performed a virtual ligand screen of a library of 10000
      members to identify compounds predicted to bind to PA and prevent its
      oligomerization. Four of these compounds slowed PA association in a FRET-based
      oligomerization assay, and two of those protected cells from intoxication at
      concentrations of 1-10 MUM. Exploration of the protective mechanism by Western
      blot showed decreased SDS-resistant PA oligomer on cells and, surprisingly,
      decreased amounts of activated PA. In vitro assays showed that one of the
      inhibitors blocked furin-mediated cleavage of PA, apparently through its binding
      to the PA substrate. Thus, we have identified inhibitors that can independently
      block both PA's cleavage by furin and its subsequent oligomerization. Lead
      optimization on these two backbones may yield compounds with high activity and
      specificity for the anthrax toxins.

PMID- 22954389
TI  - Mechanistic borderline of one-step hydrogen atom transfer versus stepwise Sc(3+)
      coupled electron transfer from benzyl alcohol derivatives to a non-heme iron(IV)
      oxo complex.
AB  - The rate of oxidation of 2,5-dimethoxybenzyl alcohol (2,5
      (MeO)(2)C(6)H(3)CH(2)OH) by [Fe(IV)(O)(N4Py)](2+) (N4Py = N,N-bis(2
      pyridylmethyl)-N-bis(2-pyridyl)methylamine) was enhanced significantly in the
      presence of Sc(OTf)(3) (OTf(-) = trifluoromethanesulfonate) in acetonitrile
      (e.g., 120-fold acceleration in the presence of Sc(3+)). Such a remarkable
      enhancement of the reactivity of [Fe(IV)(O)(N4Py)](2+) in the presence of Sc(3+)
      was accompanied by the disappearance of a kinetic deuterium isotope effect. The
      radical cation of 2,5-(MeO)(2)C(6)H(3)CH(2)OH was detected in the course of the
      reaction in the presence of Sc(3+). The dimerized alcohol and aldehyde were also
      produced in addition to the monomer aldehyde in the presence of Sc(3+). These
      results indicate that the reaction mechanism is changed from one-step hydrogen
      atom transfer (HAT) from 2,5-(MeO)(2)C(6)H(3)CH(2)OH to [Fe(IV)(O)(N4Py)](2+) in
      the absence of Sc(3+) to stepwise Sc(3+)-coupled electron transfer, followed by
      proton transfer in the presence of Sc(3+). In contrast, neither acceleration of
      the rate nor the disappearance of the kinetic deuterium isotope effect was
      observed in the oxidation of benzyl alcohol (C(6)H(5)CH(2)OH) by
      [Fe(IV)(O)(N4Py)](2+) in the presence of Sc(OTf)(3). Moreover, the rate constants
      determined in the oxidation of various benzyl alcohol derivatives by
      [Fe(IV)(O)(N4Py)](2+) in the presence of Sc(OTf)(3) (10 mM) were compared with
      those of Sc(3+)-coupled electron transfer from one-electron reductants to
      [Fe(IV)(O)(N4Py)](2+) at the same driving force of electron transfer. This
      comparison revealed that the borderline of the change in the mechanism from HAT
      to stepwise Sc(3+)-coupled electron transfer and proton transfer is dependent on
      the one-electron oxidation potential of benzyl alcohol derivatives (ca. 1.7 V vs
      SCE).

PMID- 22954390
TI  - Gold-catalyzed oxidative rearrangement of homopropargylic ether via oxonium
      ylide.
AB  - Synthetically useful alpha,beta-unsaturated carbonyl compounds were obtained from
      gold-catalyzed oxidative rearrangement of homopropargylic ether under mild
      reaction conditions. Gold carbenoid and oxonium ylide are proposed as key
      intermediates.

PMID- 22954391
TI  - Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing
      radiation exposure in nonhuman primates by mass spectrometry-based metabolomics.
AB  - Mass spectrometry-based metabolomics has previously demonstrated utility for
      identifying biomarkers of ionizing radiation exposure in cellular, mouse and rat
      in vivo radiation models. To provide a valuable link from small laboratory
      rodents to humans, gamma-radiation-induced urinary biomarkers were investigated
      using a nonhuman primate total-body-irradiation model. Mass spectrometry-based
      metabolomics approaches were applied to determine whether biomarkers could be
      identified, as well as the previously discovered rodent biomarkers of gamma
      radiation. Ultra-performance liquid chromatography-electrospray ionization
      quadrupole time-of-flight mass spectrometry analysis was carried out on a time
      course of clean-catch urine samples collected from nonhuman primates (n = 6 per
      cohort) exposed to sham, 1.0, 3.5, 6.5 or 8.5 Gy doses of (60)Co gamma ray (~0.55
      Gy/min) ionizing radiation. By multivariate data analysis, 13 biomarkers of
      radiation were discovered: N-acetyltaurine, isethionic acid, taurine, xanthine,
      hypoxanthine, uric acid, creatine, creatinine, tyrosol sulfate, 3-hydroxytyrosol
      sulfate, tyramine sulfate, N-acetylserotonin sulfate, and adipic acid. N
      Acetyltaurine, isethionic acid, and taurine had previously been identified in
      rats, and taurine and xanthine in mice after ionizing radiation exposure. Mass
      spectrometry-based metabolomics has thus successfully revealed and verified
      urinary biomarkers of ionizing radiation exposure in the nonhuman primate for the
      first time, which indicates possible mechanisms for ionizing radiation injury.

PMID- 22954392
TI  - Gene expression in low- and high-dose-irradiated human peripheral blood
      lymphocytes: possible applications for biodosimetry.
AB  - To overcome the limitations of existing biodosimetry methods, we examined dose-
      and time-dependent gene expression changes in human peripheral blood lymphocytes
      after exposure to low-, medium- and high-dose ionizing radiation and searched for
      genes suitable for predicting radiation doses in the low-dose range.
      Additionally, the experiments are intended to provide new insights into the
      biological effects of exposures to low-, medium- and high-dose radiation. Gene
      expression analysis using whole human genome DNA microarrays was performed in
      human blood from six healthy donors irradiated ex vivo with 0, 0.02, 0.1, 0.5, 1,
      2 and 4 Gy (gamma rays, (137)Cs) at 6, 24 and 48 h after high-dose exposure (0.5
      4 Gy), and at 24 and 48 h after low-dose exposures of 0.02 or 0.1 Gy. DNA
      microarray-based alterations in gene expression were found in a wide dose range
      in vitro and allowed us to identify nine genes with which low radiation doses
      could be accurately predicted with a sensitivity of 95.6%. In the low-, medium-
      and high-dose range, expression alterations increased with increasing dose and
      time after exposure, and were assigned to different biological processes such as
      nucleosome assembly, apoptosis and DNA repair response. We conclude from our
      results that gene expression profiles are suitable for predicting low-dose
      radiation exposure in a rapid and reliable manner and that acute low-dose
      exposure, as low as 20 mGy, leads to well-defined physiological responses in
      human peripheral blood lymphocytes.

PMID- 22954393
TI  - Efficacy and safety of standard-dose versus half-dose tirofiban in patients with
      non-ST elevation acute coronary syndromes undergoing early percutaneous coronary
      intervention.
AB  - INTRODUCTION: To explore the optimal dosage of tirofiban associated with double
      benefits of efficacy and safety in patients with non-ST elevation acute coronary
      syndromes (NSTE-ACS) undergoing early percutaneous coronary intervention (PCI).
      AIMS: A total of 163 patients were included in this study (78 in SD group versus
      85 in HD group). In SD (HD) group, tirofiban was administered intravenously with
      a bolus dose of 10 (5) MUg/kg within 3 min and followed by continuous intravenous
      infusion of 0.15 (0.075) MUg/kg/min for 48 h. Within 24 h on admission, patients
      underwent CAG or CAG+PCI. The angiographic results (initial TIMI, final
      TIMI/CTFC/TMPG) were evaluated. Platelet aggregation rate (PAR) was measured
      before and 2, 24, 48 h after bolus tirofiban. MACEs were evaluated at 7-day, 30
      day, and 6-month follow-up. Bleeding was observed at 7 days. RESULTS: The
      proportions of TIMI grade 3 seemed higher in SD group before and after PCI
      followed by a better myocardial perfusion, but not statistically different (P =
      0.26/0.08). PAR was lower in SD group than that in HD group at 2 h after bolus
      tirofiban (P = 0.03). MACEs were not statistically different at 7, 30 day, and 6
      month in two groups. The incidence of minor bleeding was significantly lower in
      HD group than that in SD group (8.2% vs. 20.5%, P = 0.04). The risk of bleeding
      would increase under the conditions of decreased PAR, increased dose of tirofiban
      and decreased CCr. CONCLUSION: Half-dose tirofiban was not inferior to standard
      dose in efficacy, what is more, half-dose tirofiban showed a better safety
      characteristic of lower bleeding risk. Therefore, half-dose tirofiban is
      recommended to patients with NSTE-ACS undergoing early PCI.

PMID- 22954394
TI  - Cardiopulmonary response to inhalation of secondary organic aerosol derived from
      gas-phase oxidation of toluene.
AB  - The biological response to inhalation of secondary organic aerosol (SOA) was
      determined in rodents exposed to SOA derived from the oxidation of toluene, a
      precursor emitted from anthropogenic sources. SOA atmospheres were produced to
      yield 300 ug.m(-3) of particulate matter (PM) plus accompanying gases. Whole-body
      exposures were conducted in mice to assess both pulmonary and cardiovascular
      effects. ApoE(-/-) mice were exposed for 7 days and measurements of TBARS and
      gene expression of heme-oxygenase-1 (HO-1), endothelin-1 (ET-1), and matrix
      metalloproteinase-9 (MMP-9) were made in aorta. Pulmonary inflammatory responses
      in both species were measured by bronchoalveolar lavage fluid (BALF) cell counts.
      No pulmonary inflammation was observed. A mild response was observed in mouse
      aorta for the upregulation of ET-1 and HO-1, with a trend for increased MMP-9 and
      TBARS, and. Overall, toluene-derived SOA revealed limited biological response
      compared with previous studies using this exposure protocol with other
      environmental pollutants.

PMID- 22954395
TI  - Development of multi-route physiologically-based pharmacokinetic models for
      ethanol in the adult, pregnant, and neonatal rat.
AB  - Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the USA, and
      higher EtOH concentrations are being considered (15-85%). Currently, no
      physiologically-based pharmacokinetic (PBPK) models are available to describe the
      kinetics of EtOH-based biofuels. PBPK models were developed to describe life
      stage differences in the kinetics of EtOH alone in adult, pregnant, and neonatal
      rats for inhalation, oral, and intravenous routes of exposure, using data
      available in the open literature. Whereas ample data exist from gavage and
      intravenous routes of exposure, kinetic data from inhalation exposures are
      limited, particularly at concentrations producing blood and target tissue
      concentrations associated with developmental neurotoxicity. Compared to available
      data, the three models reported in this paper accurately predicted the kinetics
      of EtOH, including the absorption, peak concentration, and clearance across
      multiple datasets. In general, model predictions for adult and pregnant animals
      matched inhalation and intravenous datasets better than gavage data. The adult
      model was initially better able to predict the time-course of blood
      concentrations than was the neonatal model. However, after accounting for age
      related changes in gastric uptake using the calibrated neonate model, simulations
      consistently reproduced the early kinetic behavior in blood. This work provides
      comprehensive multi-route life-stage models of EtOH pharmacokinetics and
      represents a first step in development of models for use with gasoline-EtOH
      blends, with additional potential applicability in investigation of the
      pharmacokinetics of EtOH abuse, addiction, and toxicity.

PMID- 22954396
TI  - Histological and immunohistochemical study of the expression of p53 and ki-67
      proteins in the mucosa of the tongue, pharynx and larynx of rats exposed to
      cigarette smoke.
AB  - INTRODUCTION: Head and neck cancers are linked to smoking. The most affected
      sites are the oral cavity, pharynx and larynx. Experimental studies show
      epithelial lesions caused by cigarette smoke. OBJECTIVES: To investigate in rats
      the effects of acute cigarette smoke exposure on the mucosa of the tongue,
      pharynx and larynx. MATERIAL AND METHOD: Wistar rats were allocated into two
      groups of 20 animals: CG (control) receiving food and water ad libitum and TG
      (Tobacco) exposed to the smoke of 40 cigarettes/day for 60 days. Biopsy of their
      tongues, pharynxes and larynxes were subjected to histopathological,
      histomorphometric and immunohistochemical studies of protein p53 and ki-67.
      RESULT: The histological analysis of tongue from the Tobacco group revealed
      epithelial hyperplasia (90%), basal cell hyperplasia (95%) and mild to moderate
      dysplasia (85%). In pharynx showed basal cell hyperplasia (85%), dysplasia (25%)
      and vascular congestion (95%). In larynx showed basal cell hyperplasia (70%),
      epithelial hyperplasia (55%), congestion (100%) and inflammatory infiltrate
      (25%). Morphometric analysis revealed that keratin layer thickness was greater in
      the tobacco group. P53 immunoexpression was negative in both groups. Ki-67
      immunoexpression was positive in basal cell nuclei but in parabasal cell nuclei
      it was positive only in the Tobacco group. CONCLUSIONS: The exposure of animals
      to cigarette smoke for 60 days resulted in benign lesions. The duration of
      exposure was not enough to cause the development cancer, as confirmed by the
      negative expression of p53 protein in all slides examined. Analysis of ki-67
      expression showed intense epithelial proliferation in response to damage.

PMID- 22954397
TI  - Pulmonary hypertension and vascular oxidative damage in cigarette smoke exposed
      eNOS(-/-) mice and human smokers.
AB  - CONTEXT: Cigarette smoke is known to be associated with pulmonary hypertension in
      humans and in animal models. Although the etiology of pulmonary hypertension in
      smokers is not understood, recent work has suggested a role for inducible nitric
      oxide synthase (iNOS) in inducing oxidative stress. OBJECTIVE AND METHODS: To
      further evaluate this question, we assessed eNOS-/- mice exposed to air or
      cigarette smoke for the presence of pulmonary hypertension and examined vascular
      remodeling and expression of nitrotyrosine, a marker of reactive nitrogen species
      induced oxidative damage, using immunohistochemistry. To ascertain whether
      oxidants may play a role in humans, we also examined lung tissue from nonsmokers,
      and patients with chronic obstructive pulmonary disease (COPD) with and without
      pulmonary hypertension. RESULTS: We found that eNOS(-/-) mice developed increased
      pulmonary arterial pressure after six months cigarette smoke exposure, and this
      was associated with vascular remodeling and increased vascular nitrotyrosine
      staining. iNOS gene expression was decreased in the pulmonary arteries of the
      smoke exposed animals, and no protein was detectable by immunohistochemistry. In
      humans, vascular nitrotyrosine staining intensity was increased in smokers with
      COPD compared to nonsmokers, and further increased in smokers with combined COPD
      and pulmonary hypertension. CONCLUSIONS: We conclude that cigarette smoke-induced
      pulmonary hypertension is associated with evidence of oxidative vascular damage
      by reactive nitrogen species, but that iNOS does not appear to be the major
      contributor to such damage. Most likely the source of reactive nitrogen species
      is the cigarette smoke itself.

PMID- 22954398
TI  - Subacute inhalation toxicity assessment of fly ash from industrial waste
      incinerators.
AB  - Fly ash from industrial waste incinerators has been a significant concern because
      of their constituent toxic heavy metals and organic compounds. The objective of
      this study was to identify the subacute inhalation toxicity of fly ash from
      industrial waste incinerators, using whole body inhalation exposure chambers.
      Male and female groups of Sprague-Dawley rats were exposed to fly ash by
      inhalation of concentrations of 0, 50, 100, 200 mg/m(3), for 6 h/day, 5 days/week
      for 4 weeks. There was no significant difference in body weight, and relative
      organ weight to body weight, between the exposure groups and the control group.
      Hematological examinations revealed a significant increase of monocyte counts in
      fly ash exposed rats and brown pigment laden macrophage was found in the lungs of
      rats exposed to high concentration of fly ash. A decrease of blood glucose levels
      and an increase in glutamate oxaloacetate transaminase activity were observed in
      fly ash treated rats. There was also a significant increase of lactate
      dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent
      increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage,
      liver, lung, and thymus of rats exposed to fly ash. In addition, the level of
      lipid peroxidation was increased in the plasma of rats exposed to a high
      concentration of fly ash. These results suggest that inhalation of fly ash from
      industrial waste incinerators can induce histopathologic, hematological, and
      serum biochemical changes and oxidative damage.

PMID- 22954399
TI  - Aggravating effects of Asian sand dust on lung eosinophilia in mice immunized
      beforehand by ovalbumin.
AB  - Asian sand dust (ASD) event may result in a significant influence on an asthmatic
      patient. However, for obvious reasons, there is no experimental study in which
      asthmatic patients are exposed to ASD. This study was undertaken to clarify the
      effects of ASD on lung eosinophiliain mice immunized beforehand by ovalbumin
      (OVA). CD-1 mice were instilled intratracheally with OVA four times at 2-week
      intervals. Simultaneous intratracheal administration of OVA and ASD (OVA + ASD
      sim) at the last OVA treatment or intratracheal administration with ASD 1 day
      before (OVA + ASD pre) /after (OVA + ASD post) the last OVA treatment was
      performed to investigate the effects of OVA and ASD exposure timing. The three
      kinds of treatment (OVA + ASD pre; OVA + ASD sim; OVA + ASD post) aggravated
      allergic lung inflammation and proliferation of goblet cells in the airway
      epithelium in mice, as evidenced by the cellular profile of bronchoalveolar
      lavage fluid (BALF) and pathological examination. As an overall trend, these
      changes were paralleled with the expression of Th2-associated effecter molecules
      and eosinophil relevant cytokine chimokines in BALF as well as the production of
      OVA-specific IgG1 compared with OVA treatment alone. OVA + ASD sim aggravated
      lung eosinophilia remarkably compared with the other treatments. The order of the
      potency of the aggravation was OVA+ASD pre < OVA+ASD post <OVA+ASD sim. These
      results indicate that ASD has a potent effect in activating lung eosinopilia in
      mice immunized beforehand by OVA. The simultaneous exposure of asthmatic patients
      to ASD and its antigen may have serious consequences for such individuals.

PMID- 22954400
TI  - Halomethane-induced cytotoxicity and cell proliferation in human lung MRC-5
      fibroblasts and NL20-TA epithelial cells.
AB  - Halomethanes (HMs) can be formed during the chlorination process to obtain
      drinking water. In liver cells, HMs had been shown to be mutagenic and
      carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required.
      Although inhalation is the most common pathway of exposure, reports on the toxic
      effects induced by HMs in human lung are contradictory. The aim of this study was
      therefore to evaluate in vitro cytotoxicity and cell proliferation induced by
      CH(2)Cl(2), CHCl(3) and BrCHCl(2) in human lung NL20-TA epithelial cells and MRC
      5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High
      concentrations of these HMs induced cytotoxicity, particularly in cells treated
      with BrCHCl(2). Low concentrations of BrCHCl(2) stimulated hyperproliferation of
      fibroblasts, the most probable consequence of which is regenerative proliferation
      related to collagen induction. Fibroblasts exposed to BrCHCl(2) exhibited low
      levels of CYP 2E1 activity suggesting that released bromine is able to alter this
      activity by affecting the active site or auto regulating the activity itself.
      GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating
      that potential lung damage is due to formation of pro-carcinogens such as
      formaldehyde.

PMID- 22954401
TI  - Comparison of deposited surface area of airborne ultrafine particles generated
      from two welding processes.
AB  - This article describes work performed on the assessment of the levels of airborne
      ultrafine particles emitted in two welding processes metal-active gas (MAG) of
      carbon steel and friction-stir welding (FSW) of aluminium in terms of deposited
      area in alveolar tract of the lung using a nanoparticle surface area monitor
      analyser. The obtained results showed the dependence from process parameters on
      emitted ultrafine particles and clearly demonstrated the presence of ultrafine
      particles, when compared with background levels. The obtained results showed that
      the process that results on the lower levels of alveolar-deposited surface area
      is FSW, unlike MAG. Nevertheless, all the tested processes resulted in important
      doses of ultrafine particles that are to be deposited in the human lung of
      exposed workers.

PMID- 22954402
TI  - Coexisting phases in PEGylated phosphocholine membranes: a model study.
AB  - Understanding the phase behavior of PEGylated phosphocholine membranes is
      becoming increasingly important in many biomedical applications. Here, we used
      binary mixtures of phosphocholines and PEG-phospholipids in monolayers on
      phosphate buffered saline as ideal models of PEGylated phosphocholine membranes.
      Several phase states and transitions between homogeneously mixed and completely
      immiscible phases have been visualized in these mixtures by epifluorescence
      microscopy, which is neither predicted nor easily explained by the existing
      interpretive schemes. The results of our study suggest that the phase state of
      PEGylated phosphocholine membranes may drastically vary depending on factors such
      as aliphatic chain length on phosphocholines and PEG-phospholipids, PEG content,
      and temperature. These findings are summarized in phase drawings and diagrams to
      demonstrate a striking variety of possible phases. The diagrams can also be
      instrumental in predicting the phase state of PEGylated phosphocholine membranes,
      in particular under physiological conditions.

PMID- 22954403
TI  - Colistin vs. the combination of colistin and rifampicin for the treatment of
      carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia.
AB  - The aim of this study was to compare the responses of colistin treatment alone
      vs. a combination of colistin and rifampicin in the treatment of ventilator
      associated pneumonia (VAP) caused by a carbapenem-resistant A. baumannii strain.
      Forty-three patients were randomly assigned to one of two treatment groups.
      Although clinical (P = 0.654), laboratory (P = 0.645), radiological (P = 0.290)
      and microbiological (P = 0.597) response rates were better in the combination
      group, these differences were not significant. However, time to microbiological
      clearance (3.1 +/- 0.5 days, P = 0.029) was significantly shorter in the
      combination group. The VAP-related mortality rates were 63.6% (14/22) and 38.1%
      (8/21) for the colistin and the combination groups (P = 0.171), respectively. Our
      results suggest that the combination of colistin with rifampicin may improve
      clinical and microbiological outcomes of VAP patients infected with A. baumannii.

PMID- 22954405
TI  - Assessment of left atrial function in hypertrophic cardiomyopathy and athlete's
      heart: a left atrial myocardial deformation study.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death
      in athletes and differentiating this condition from the nonpathological
      "athlete's heart" remains a challenge. The development of pathological left
      ventricular hypertrophy (LVH) is associated with left atrial (LA) dilatation and
      dysfunction. LA strain and strain rate by two-dimensional (2D) speckle tracking
      are novel indices of LA function and might contribute to differentiate
      physiological from pathological LVH among athletes with underdiagnosed HCM.
      METHODS: We evaluated 20 patients with nonobstructive HCM, 20 highly trained
      athletes and 20 healthy controls matched for age, gender, and body surface area.
      All patients underwent a transthoracic echocardiogram with evaluation of LA
      strain: s-wave (LASs); and strain rate: s-wave (LASRs) and a-wave (LASRa).
      RESULTS: LV mass index, LA volume index, and ejection fraction were comparable
      between patients with HCM and athletes. Patients with HCM had a significantly
      lower LASs (19 + 8% vs. 43 + 8%, P < 0.01), LASRs (0.7 + 0.2 s-1 vs. 1.6 + 0.2 s
      1, P < 0.01), and LASRa (-0.8 + 0.1 s-1 vs. -1.4 + 0.3 s-1, P < 0.01) compared to
      athletes. Among hypertrophic subjects, independent predictors of hypertrophy
      related to HCM were LASs and E/e ratio. CONCLUSIONS: LA myocardial deformation is
      significantly impaired in patients with HCM compared to athletes and healthy
      controls. LA strain and strain rate assessed by 2D speckle tracking should be
      incorporated in the evaluation of trained athletes with LVH and LA dilatation.

PMID- 22954408
TI  - The population genetics of cooperative gene regulation.
AB  - BACKGROUND: Changes in gene regulatory networks drive the evolution of phenotypic
      diversity both within and between species. Rewiring of transcriptional networks
      is achieved either by changes to transcription factor binding sites or by changes
      to the physical interactions among transcription factor proteins. It has been
      suggested that the evolution of cooperative binding among factors can facilitate
      the adaptive rewiring of a regulatory network. RESULTS: We use a population
      genetic model to explore when cooperative binding of transcription factors is
      favored by evolution, and what effects cooperativity then has on the adaptive re
      writing of regulatory networks. We consider a pair of transcription factors that
      regulate multiple targets and overlap in the sets of target genes they regulate.
      We show that, under stabilising selection, cooperative binding between the
      transcription factors is favoured provided the amount of overlap between their
      target genes exceeds a threshold. The value of this threshold depends on several
      population-genetic factors: strength of selection on binding sites, cost of
      pleiotropy associated with protein-protein interactions, rates of mutation and
      population size. Once it is established, we find that cooperative binding of
      transcription factors significantly accelerates the adaptive rewiring of
      transcriptional networks under positive selection. We compare our qualitative
      predictions to systematic data on Saccharomyces cerevisiae transcription factors,
      their binding sites, and their protein-protein interactions. CONCLUSIONS: Our
      study reveals a rich set of evolutionary dynamics driven by a tradeoff between
      the beneficial effects of cooperative binding at targets shared by a pair of
      factors, and the detrimental effects of cooperative binding for non-shared
      targets. We find that cooperative regulation will evolve when transcription
      factors share a sufficient proportion of their target genes. These findings help
      to explain empirical pattens in datasets of transcription factors in
      Saccharomyces cerevisiae and, they suggest that changes to physical interactions
      between transcription factors can play a critical role in the evolution of gene
      regulatory networks.

PMID- 22954409
TI  - Non-alcoholic acute Wernicke's encephalopathy: role of MRI in non typical cases.
AB  - AIM: Acute Wernicke's encephalopathy (WE) is a severe neurological disorder
      caused by thiamine deficiency, most commonly found in chronic alcoholics. It is
      not so easy to suspect acute WE when the clinical picture does not include all
      the typical symptoms and alcohol abuse is not reported. Three rare cases of
      Wernicke's encephalopathy (WE) in non-alcoholic patients are reported. CASES
      PRESENTATION: Two patients developed the disease following prolonged intravenous
      feeding, the third was carrying a gastric lymphoma. None of them presented with
      the classic clinical triad of WE (ophtalmoplegia/nystagmus, ataxia and
      consciousness disturbance), showing just one or two of the typical symptoms.
      Brain Magnetic Resonance Imaging (MRI) represented the key tool to suspect and
      define WE diagnosis, showing a picture characterized by bilaterally altered
      signal of the thalamic pulvinar, mesencephalic cup, mammillary bodies,
      periaqueductal grey matter and floor of fourth ventricle. All patients
      dramatically improved within 48 h after administration of thiamine. CONCLUSION:
      We emphasize that WE should be suspected in all patients showing typical MRI
      features presenting with at least one of the clinical triad of WE.

PMID- 22954410
TI  - Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI:
      correlation with clinical and pathological features.
AB  - PURPOSE: To retrospectively determine whether the hyperintense hepatocellular
      carcinomas (HCCs) seen on the hepatobiliary phase of gadoxetic acid-enhanced MR
      imaging (EOB-MRI) might have different histologic characteristics from usual
      hypointense HCCs. MATERIALS AND METHODS: Two hundred three surgically proven HCCs
      from 192 patients who underwent preoperative EOB-MRI were analyzed. The
      demographic and histologic characteristics of hyperintense HCCs were compared
      with usual hypointense HCCs by using the t-test or Fisher's exact test. RESULTS:
      By visual assessment, 18 (8.8%) tumors were classified as hyperintense HCCs.
      Patients with hyperintense HCC were significantly (p<0.05) older (60.1 vs. 55.2
      years) than those with hypointense HCCs. Hyperintense HCCs showed significantly
      lower rate of microvascular invasion (27.8% vs. 53.5%) and significantly higher
      rate of peliosis (61.1% vs. 30.8%). Hyperintense HCCs were more frequently
      expanding type, and none showed infiltrative type or scirrhous histologic
      pattern. CONCLUSIONS: Hyperintense HCCs seem to have clinical and histologic
      features that might be related with more favorable outcomes.

PMID- 22954411
TI  - Computed tomography hepatic arteriography has a hepatic falciform artery
      detection rate that is much higher than that of digital subtraction angiography
      and 99mTc-MAA SPECT/CT: implications for planning 90Y radioembolization?
AB  - PURPOSE: To compare the hepatic falciform artery (HFA) detection rates of digital
      subtraction angiography (DSA), computed tomography hepatic arteriography (CTHA)
      and 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed
      tomography with integrated CT (SPECT/CT) and to correlate HFA patency with
      complication rates of yttrium-90 (90Y) radioembolization. MATERIAL AND METHODS:
      From August 2008 to November 2010, 79 patients (range 23-83 years, mean 62.3
      years; 67 male) underwent pre-treatment DSA, CTHA and 99mTc-MAA scintigraphy
      (planar/SPECT/CT) to assess suitability for radioembolization with 90Y resin
      microspheres. Thirty-seven patients were excluded from the study, because CTHA
      was performed with a catheter position that did not result in opacification of
      the liver parenchyma adjacent to the falciform ligament. DSA, CTHA and 99mTc-MAA
      SPECT/CT images and medical records were retrospectively reviewed. RESULTS: A
      patent HFA was detected in 22 of 42 patients (52.3%). The HFA detection rates of
      DSA, CTHA and 99mTc-MAA SPECT/CT were 11.9%, 52.3% and 13.3%, respectively
      (p<0.0001). An origin from the segment 4 artery was seen in 51.7% of HFAs.
      Prophylactic HFA coil-embolization prior to 90Y microspheres infusion was
      performed in 2 patients. Of the patients who underwent radioembolization with a
      patent HFA, none developed supra-umbilical radiation dermatitis. One patient
      experienced epigastric pain attributed to post-embolization syndrome and was
      managed conservatively. CONCLUSION: The HFA detection rate of CTHA is superior to
      that of DSA and 99mTc-MAA SPECT/CT. Complications related to non-target radiation
      of the HFA vascular territory rarely occur, even in patients undergoing
      radioembolization with a patent HFA.

PMID- 22954412
TI  - Necrotic cervical nodes: usefulness of diffusion-weighted MR imaging in the
      differentiation of suppurative lymphadenitis from malignancy.
AB  - PURPOSE: The purpose of this study was to assess the efficacy of diffusion
      weighted (DW) MR imaging for the differentiation between suppurative
      lymphadenitis and malignancy in necrotic cervical lymph nodes. MATERIALS AND
      METHODS: Fifteen patients with suppurative lymphadenitis, 40 with squamous cell
      carcinoma (SCC), eight with lymphoma, and six with thyroid cancer were
      accompanied by necrotic cervical nodes. All 69 patients underwent 1.5-T MR
      imaging including DW and 58 underwent gadolinium-enhanced MR imaging. Necrotic
      area-to-spinal cord signal intensity ratios (SIR) on T1-, T2- and DW images and
      apparent diffusion coefficients (ADCs) [10(-3)mm(2)/s] were correlated with the
      pathologies. RESULTS: Nineteen necrotic cervical nodes with suppurative
      lymphadenitis, 67 with SCC, 10 with lymphoma, and 12 with thyroid cancer were
      identified. SIR on DW images was higher in suppurative lymphadenitis (2.50 +/-
      1.21) than in malignancies (1.29 +/- 0.67) (p<.01), and ADC value was lower in
      suppurative lymphadenitis (0.89 +/- 0.21) than in malignancies (1.46 +/- 0.46)
      (p<.01). SIR on T1-weighted images was higher in thyroid cancer (1.95 +/- 0.53)
      than in suppurative lymphadenitis (0.87 +/- 0.17), SCC (0.92 +/- 0.13), and
      lymphoma (0.95 +/- 0.09) (p<.01). No significant difference in SIR on T2-weighted
      images was found between suppurative lymphadenitis (1.46 +/- 0.50) and
      malignancies (1.61 +/- 0.56). CONCLUSION: DW imaging with ADC measurements may
      play a supplementary role in the differentiation of necrotic cervical nodes
      between suppurative lymphadenitis and malignancy.

PMID- 22954414
TI  - Rearrangements of acyl, thioacyl, and imidoyl (thio)cyanates to
      iso(thio)cyanates, acyl iso(thio)cyanates to (thio)acyl isocyanates, and imidoyl
      iso(thio)cyanates to (thio)acyl carbodiimides, RCX-YCN ? RCX-NCY ? RCY-NCX ? RCY
      XCN (X and Y = O, S, NR').
AB  - Two types of rearrangements have been investigated computationally at the B3LYP/6
      311+G(d,p) level. The activation barriers for rearrangement of acyl thiocyanates
      RCO-SCN to the corresponding isothiocyanates RCO-NCS are 30-31 kcal/mol in
      agreement with the observation that the thiocyanates are in some cases isolable
      albeit very sensitive compounds. Alkoxycarbonyl-, (alkylthio)carbonyl- and
      carbamoyl thiocyanates are isolable and have higher calculated barriers (ca. 40
      kcal/mol) toward rearrangement to isothiocyanates, whereas all thioacyl
      thiocyanate derivatives are rather unstable compounds with barriers in the range
      20-30 kcal/mol for rearrangement to the isothiocyanates. Acyl-, alkoxycarbonyl-,
      and carbamoyl cyanates R-CO-OCN are predicted to be in some cases isolable
      compounds with barriers up to ca. 40 kcal/mol for rearrangement to the
      isocyanates RCO-NCO. All of the rearrangements of this type involve the HOMO of a
      nearly linear (thio)cyanate anion and the LUMO of the acyl cation, in particular
      the acyl C?X pi* orbital. The second type of rearrangement involves 1,3-shifts of
      the groups R attached to the (thio)acyl groups, that is, acyl isothiocyanate
      thioacyl isocyanate and imidoyl isothiocyanate-thioacyl carbodiimide
      rearrangements. These reactions involve four-membered cyclic, zwitterionic
      transition states facilitated by lone pair-LUMO interactions between the
      migrating R group and the neighboring iso(thio)cyanate function. Combination of
      the two rearrangements leads to the general reaction scheme RCX-YCN ? RCX-NCY ?
      RCY-NCX ? RCY-XCN (X and Y = O, S, NR').

PMID- 22954413
TI  - QseC controls biofilm formation of non-typeable Haemophilus influenzae in
      addition to an AI-2-dependent mechanism.
AB  - Non-typeable Haemophilus influenzae (NTHi) is a common pathogen associated with
      diseases such as acute otitis media or exacerbations in patients with chronic
      obstructive pulmonary disease. The biofilm-forming capability substantially
      contributes to the persistence of NTHi. However, the regulation of biofilm
      formation is not completely understood. Quorum sensing regulated by autoinducer-2
      produced by luxS is until now the only described regulatory mechanism. In this
      study, we show that the two-component signalling system QseB/C is involved in the
      biofilm formation of NTHi in vitro. An isogenic NTHi mutant of qseC (Hi3655KR2)
      showed a significant decrease in biofilm formation under static and semi-static
      conditions as assessed by crystal violet staining. In addition, under constant
      flow conditions, Hi3655KR2 formed less biofilm after 48 h. The biofilm defects
      were irrespective of autoinducer-2 levels. Hence, here we suggest for the first
      time a regulatory circuit in NTHi, which controls biofilm formation by mechanisms
      other than or in addition to luxS-dependent factors.

PMID- 22954415
TI  - The indicators of high risk on admission electrocardiography in patients with
      anterior wall ST-elevation myocardial infarction.

PMID- 22954416
TI  - Dilation of peripheral vessels in Marfan syndrome: importance of thoracoabdominal
      MR angiography.
AB  - OBJECTIVES: Aim of this study was to assess vascular morphology and dimension of
      the entire aorta and branch vessels in MFS using thoracoabdominal MR angiography
      (MRA). BACKGROUND: Evaluation of vascular involvement in Marfan Syndrome (MFS) is
      focused to the ascending aorta, which has the major risk of dissection/rupture.
      METHODS: From March 2006 to January 2011, 64 patients (35 +/- 13 years old) with
      MFS underwent echocardiography and MRA of thoracic and abdominal aorta.
      Measurements of ascending aorta, aortic arch, descending thoracic and abdominal
      aorta, and aortic branch vessels were assessed. In patients with aortic
      dissection only non dissected vessels were considered for measurements. RESULTS:
      64 Marfan patients were divided into 2 groups: patients in natural history (group
      A, 55%) and patients previously submitted to aortic root and/or ascending aorta
      replacement because of severe aortic dilation or dissection (group B, 45%).
      Dilation of the descending aorta, mostly of the aortic isthmus, occurred in 18/53
      patients (8/35 group A, 10/18 group B). Abdominal aorta resulted in the normal
      range in group A and in 16/18 patients of group B, while iliac vessels were
      dilated in 7/35 patients of group A and in 10/23 patients of group B. Four
      patients of group B presented isolated dilation of subclavian, celiac,
      mesenteric, or renal arteries. CONCLUSIONS: Vascular dilation beyond the aortic
      root is not uncommon in MFS. The systematic use of MRA provides a comprehensive
      evaluation of the entire arterial system.

PMID- 22954417
TI  - Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer.
AB  - BACKGROUND: MicroRNAs are aberrantly expressed and correlate with tumourigenesis
      and the progression of solid tumours. The miR-200 family determines the
      epithelial phenotype of cancer cells and regulates invasiveness and migration.
      Thus, we hypothesised that the quantitative detection of the miR-200 family as
      epithelial-specific microRNAs in the blood could be a useful clinical biomarker
      for gastric cancer (GC). METHODS: We initially validated the expression levels of
      miR-200a, 200b, 200c and 141 in GC cell lines (n = 2) and blood from healthy
      controls (n = 19) using real-time quantitative reverse transcription PCR (qRT
      PCR). The microarray expression profiles of the miR-200 family in 160 paired
      samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress
      and analysed. MiR-200c was selected for clinical validation. The qRT-PCR
      prospective assessment of miR-200c was performed using 67 blood samples (52 stage
      I-IV GC patients and 15 controls); the area under the receiver operating
      characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow
      Wilcoxon tests were used to assess the correlation of miR-200c with overall and
      progression-free survival (OS and PFS). Multivariate analyses were performed
      using the Cox model. RESULTS: The miR-200c blood expression levels in GC patients
      were significantly higher than in normal controls (p = 0.018). The AUC-ROC was
      0.715 (p = 0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100%
      and 73.1%, respectively, were observed. The levels of miR-200c in the blood above
      the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients,
      20.6% of stage III patients and 67.7% of stage IV patients (p < 0.001). The miR
      200c expression levels were not associated with clinical or pathological
      characteristics or recent surgical procedures. There was a correlation (p =
      0.016) with the number of lymph node metastases and the increased expression
      levels of miR-200c in blood were significantly associated with a poor OS (median
      OS, 9 vs 24 months; p = 0.016) and PFS (median PFS, 4 vs 11 months; p = 0.044).
      Multivariate analyses confirmed that the upregulation of miR-200c in the blood
      was associated with OS (HR = 2.24; p = 0.028) and PFS (HR = 2.27; p = 0.028),
      independent of clinical covariates. CONCLUSIONS: These data suggest that
      increased miR-200c levels are detected in the blood of gastric cancer patients.
      MiR-200c has the potential to be a predictor of progression and survival.

PMID- 22954418
TI  - Intramuscular and topical treatment of cutaneous leishmaniasis lesions in mice
      infected with Leishmania amazonensis using coumarin (-) mammea A/BB.
AB  - Treatment of cutaneous leishmaniasis remains limited to a few available options.
      Recent studies showed in vitro antileishmanial activity of (-) mammea A/BB, a
      coumarin isolated from leaves of Calophyllum brasiliense. Moreover, the
      dichloromethane crude extract and hexane fraction from this plant demonstrated in
      vivo activity in mice infected with Leishmania amazonensis. We evaluated the
      antileishmanial activity of (-) mammea A/BB in the L. amazonensis BALB/c mice
      model. The animals were given intramuscular and topical treatment with (-) mammea
      A/BB for 30 consecutive days. The results demonstrated that 18mg/kg/d
      intramuscularly or 0.2% topically of (-) mammea A/BB significantly reduced the
      size of skin lesions in footpads of mice compared with those in the control group
      (p<0.05). The activity of Glucantime((r)) (corresponding to 27mg/kg/d of
      pentavalent antimony) administered intramuscularly was similar to that of (-)
      mammea A/BB (p<0.05) by both routes of administration. The histopathological
      evaluation showed no changes in the organs analyzed. These results indicate that
      the coumarin obtained from C. brasiliense is the antileishmanially active
      compound and can be used to control the development of cutaneous leishmaniasis
      lesions caused by L. amazonensis.

PMID- 22954419
TI  - Role of proteases in extra-oral digestion of a predatory bug, Andrallus
      spinidens.
AB  - Roles of salivary proteases in the extra-oral digestion of the predatory bug,
      Andrallus spinidens Fabricius (Hemiptera: Pentatomidae) were studied by using 2%
      azocasein as a general substrate and specific protease substrates, as well as
      synthetic and endogenous inhibitors. It was found that salivary glands of A.
      spinidens have two anterior, two lateral, and two posterior lobes. Azocasein was
      used to measure the activity of general proteases in the salivary glands using
      different buffer solutions. The enzyme had the highest activity at pH 8. General
      protease activity was highest at 40  degrees C and was stable for 6-16 hours. The
      use of specific substrates showed that trypsin-like, chymotrypsin-like,
      aminopeptidase, and carboxypeptidase are the active proteases present in salivary
      glands, by the maximum activity of trypsin-like protease in addition to their
      optimal pH between 8-9. Ca(2+) and Mg(2+) increased proteolytic activity about
      216%, while other ions decreased it. Specific inhibitors including SBTI, PMSF,
      TLCK, and TPCK significantly decreased enzyme activity, as well as the specific
      inhibitors of methalloproteases including phenanthroline, EGTA, and TTHA.
      Extracted endogenous trypsin inhibitors extracted from potential prey, Chilo
      suppressalis, Naranga aenescens, Pieris brassicae, Hyphantria cunea, and Ephestia
      kuhniella, had different effects on trypsin-like protease activity of A.
      spinidens salivary glands. With the exception of C. suppressalis, the endogenous
      inhibitors significantly decreased enzyme activity in A. spinidens.

PMID- 22954420
TI  - Improved apportionment of ambient PM constituents to sources in Tampa, FL, with
      pseudo-deterministic receptor model-II.
AB  - In 2005, Park et al. developed a new Pseudo-Deterministic Receptor Model (PDRM)
      to apportion SO2 and ambient particulate matter (PM) constituents to local
      sources near Tampa Bay. Ambient pollutant measurements were fit to products of
      emission rates and dispersion factors constrained with a Gaussian Plume Model for
      individual sources. Although highly successful, ambient pollutant concentrations
      were affected by numerous contributing sources at a variety of distances and
      trajectories were complicated by shifting winds. In this work, we expanded the
      data set, modified the basic bilinear Gaussian filter equation to constrain
      solutions based on composition and temporal profiles of key marker species, and
      implemented a hierarchical approach to applying constraints in order of most-to
      least stringent. To account for shifting winds and differing transport times for
      ground and elevated components of plumes from distant sources, a multiple-height
      trajectory method was implemented. These changes allowed the number of unknowns
      to be expanded, such that temporal profiles of the Gaussian dispersion terms
      could also be extracted from the data. Fits for all species were substantially
      improved, as was agreement with literature sources for both emission rates and
      source-particle compositions.

PMID- 22954421
TI  - Construction of (CuX)2n cluster-containing (X = Br, I; n = 1, 2) coordination
      polymers assembled by dithioethers ArS(CH2)(m)SAr (Ar = Ph, p-Tol; m = 3, 5):
      effect of the spacer length, aryl group, and metal-to-ligand ratio on the
      dimensionality, cluster nuclearity, and the luminescence properties of the metal
      organic frameworks.
AB  - Reaction of CuI with bis(phenylthio)propane in a 1:1 ratio yields the two
      dimensional coordination polymer [{Cu(MU(2)-I)(2)Cu}{MU-PhS(CH(2))(3)SPh}(2)](n)
      (1). The 2D-sheet structure of 1 is built up by dimeric Cu(2)I(2) units, which
      are connected via four bridging 1,3-bis(phenylthio)propane ligands. In contrast,
      treatment of 2 equiv of CuI with 1,3-bis(phenylthio)propane in MeCN solution
      affords in a self-assembly reaction the strongly luminescent metal-organic 2D
      coordination polymer [Cu(4)I(4){MU-PhS(CH(2))(3)Ph}(2)](n) (2), in which cubane
      like Cu(4)(MU(3)-I)(4) cluster units are linked by the dithioether ligands. The
      crystallographically characterized one-dimensional (1D) compound [{Cu(MU(2)
      Br)(2)Cu}{MU-PhS(CH(2))(3)SPh}(2)](n) (3) is obtained using CuBr. The outcome of
      the reaction of PhS(CH(2))(5)SPh with CuI also depends of the metal-to-ligand
      ratio employed. Mixing CuI and the dithioether in a 2:1 ratio results in
      formation of [Cu(4)I(4){MU-PhS(CH(2))(5)Ph}(2)](n) (4) in which cubane-like
      Cu(4)(MU(3)-I)(4) clusters are linked by the bridging dithioether ligand giving
      rise to a 1D necklace structure. A ribbon-like 1D-polymer with composition
      [{Cu(MU(2)-I)(2)Cu}{MU-PhS(CH(2))(5)SPh}(2)](n) (5), incorporating rhomboid
      Cu(2)I(2) units, is produced upon treatment of CuI with 1,5
      bis(phenylthio)pentane in a 1:1 ratio. Reaction of CuBr with PhS(CH(2))(5)SPh
      produces the isomorphous 1D-compound [{Cu(MU(2)-Br)(2)Cu}{MU
      PhS(CH(2))(5)SPh}(2)](n) (6). Strongly luminescent [Cu(4)I(4){MU-p
      TolS(CH(2))(5)STol-p}(2)](n) (7) is obtained after mixing 1,5-bis(p
      tolylthio)pentane with CuI in a 1:2 ratio, and the 2D-polymer [{Cu(MU(2)
      I)(2)Cu}(2){MU-p-TolS(CH(2))(5)STol-p}(2)](n) (8) results from reaction in a 1:1
      metal-to-ligand ratio. Under the same reaction conditions, 1D-polymeric
      [{Cu(MU(2)-Br)(2)Cu}{MU-p-TolS(CH(2))(5)STol-p}(2)](n) (9) is formed using CuBr.
      This study reveals that the structure of the self-assembly process between CuX
      and ArS(CH(2))(m)SAr ligands is hard to predict. The solid-state luminescence
      spectra at 298 and 77 K of 2 and 4 exhibit very strong emissions around 535 and
      560 nm, respectively, whereas those for 1 and 5 display weaker ones at about 450
      nm. The emission lifetimes are longer for the longer wavelength emissions (>1.0
      MUs arising from the cubane species) and shorter for the shorter wavelength ones
      (<1.4 MUs arising from the rhomboid units). The Br-containing species are found
      to be weakly fluorescent.

PMID- 22954423
TI  - Theoretical studies of spectroscopy and dynamics of hydrated electrons.

PMID- 22954422
TI  - Pressure overload induces early morphological changes in the heart.
AB  - Cardiac hypertrophy, whether pathological or physiological, induces a variety of
      additional morphological and physiological changes in the heart, including
      altered contractility and hemodynamics. Events exacerbating these changes are
      documented during later stages of hypertrophy (usually termed pathological
      hypertrophy). Few studies document the morphological and physiological changes
      during early physiological hypertrophy. We define acute cardiac remodeling events
      in response to transverse aortic constriction (TAC), including temporal changes
      in hypertrophy, collagen deposition, capillary density, and the cell populations
      responsible for these changes. Cardiac hypertrophy induced by TAC in mice was
      detected 2 days after surgery (as measured by heart weight, myocyte width, and
      wall thickness) and peaked by day 7. Picrosirius staining revealed increased
      collagen deposition 7 days after TAC; immunostaining and flow cytometry indicated
      a concurrent increase in fibroblasts. The findings correlated with angiogenesis
      in TAC hearts; a decrease in capillary density was observed at day 2, with
      recovery to sham-surgery levels by day 7. Increased pericyte levels, which were
      observed 2 days after TAC, may mediate this angiogenic transition. Gene
      expression suggests a coordinated response in growth, extracellular matrix, and
      angiogenic factors to mediate the observed morphological changes. Our data
      demonstrate that morphological changes in response to cardiovascular injury occur
      rapidly, and the present findings allow correlation of specific events that
      facilitate these changes.

PMID- 22954424
TI  - Rhodium-catalyzed [2 + 2] cycloaddition of ynamides with nitroalkenes.
AB  - In the presence of a diene-ligated rhodium complex, ynamides and nitroalkenes
      undergo catalytic [2 + 2] cycloadditions to provide cyclobutenamides. The
      presence of sodium tetraphenylborate was found to be crucial for the reactions to
      proceed efficiently.

PMID- 22954425
TI  - Maternal and newborn outcomes following uterine rupture among women without
      versus those with a prior cesarean.
AB  - OBJECTIVE: To compare outcomes from uterine ruptures (UR) among women without
      versus with a prior cesarean. METHOD: This case-control study matched on
      gestational age +/- 1 week and birth year +/- 2 years using a variable numbers of
      controls (maximum = 4) for each case. All URs in Massachusetts between 1990 and
      1998 were identified using ICD-9 codes from linked hospital discharge and
      birth/fetal death certificate files and confirmed by medical record review.
      Complete hospitalization records were abstracted. Maternal outcomes were
      hysterectomy, transfusion, ICU admission, shock, assisted ventilation, and
      hospital length of stay. Infant outcomes were 5 min Apgar less than 3 or need for
      ventilation at birth, death, or poor prognosis at discharge. RESULTS: The UR
      incidence in women without a prior cesarean was 7 per 100,000 births. Of the 49
      women without a prior cesarean and a UR, 36 women met study criteria and were
      matched to 140 controls. Women without a prior cesarean had more severe maternal
      morbidity (50% vs. 16%) (adj OR 3.28, 95% CI: 1.70, 6.32) with 47% of cases
      requiring transfusion and 33% requiring ICU admission. Their hospital stays were
      nearly two days longer. Among their infants, 14% died or had a poor prognosis at
      discharge compared to 7% of control infants (OR = 2.42, 95% CI 0.94, 6.28).
      CONCLUSION: Although UR in a woman without a prior cesarean is uncommon,
      providers should be prepared for more severe maternal morbidity which may be
      mitigated by prompt surgical intervention and heightened hemodynamic
      surveillance.

PMID- 22954426
TI  - Evaluation of combined prescription of rocker sole shoes and custom-made foot
      orthoses for the treatment of plantar fasciitis.
AB  - BACKGROUND: It is a routine practice to prescribe a combination of rocker shoes
      and custom-made foot orthoses for patients with plantar fasciitis. Recently,
      there has been a debate on this practice, and studies have shown that the
      individual prescription of rocker shoes or custom-made foot orthoses is effective
      in treating plantar fasciitis. The aim of this study was to evaluate and compare
      the immediate therapeutic effects of individually prescribed rocker sole shoes
      and custom-made foot orthoses, and a combined prescription of them on plantar
      fasciitis. METHODS: This was a cross-over study. Fifteen patients with unilateral
      plantar fasciitis were recruited; they were from both genders and aged between 40
      and 65. Subjects performed walking trials which consisted of one 'unshod'
      condition and four 'shod' conditions while wearing baseline shoes, rocker shoes,
      baseline shoes with foot orthotics, and rocker shoes with foot orthotics. The
      study outcome measures were the immediate heel pain intensity levels as reflected
      by visual analog scale pain ratings and the corresponding dynamic plantar
      pressure redistribution patterns as evaluated by a pressure insole system.
      RESULTS: The results showed that a combination of rocker shoes and foot orthoses
      produced a significantly lower visual analog scale pain score (9.7 mm) than
      rocker shoes (30.9 mm) and foot orthoses (29.5 mm). With regard to baseline
      shoes, it also significantly reduced the greatest amount of medial heel peak
      pressure (-33.58%) without overloading other plantar regions when compared to
      rocker shoes (-7.99%) and foot orthoses (-28.82%). DISCUSSION: The findings
      indicate that a combined prescription of rocker sole shoes and custom-made foot
      orthoses had greater immediate therapeutic effects compared to when each
      treatment had been individually prescribed.

PMID- 22954427
TI  - Motor variability in occupational health and performance.
AB  - Several recent reviews have reported that 'repetitive movements' constitute a
      risk factor for occupational musculoskeletal disorders in the neck, shoulder and
      arm regions. More variation in biomechanical exposure is often suggested as an
      effective intervention in such settings. Since increasing variation using
      extrinsic methods like job rotation may not always be possible in an industrial
      context, the intrinsic variability of the motor system may offer an alternative
      opportunity to increase variation. Motor variability refers to the natural
      variation in postures, movements and muscle activity observed to different
      extents in all tasks. The current review discusses research appearing in motor
      control, sports sciences and occupational biomechanics literature to answer
      whether motor variability is important to consider in an occupational context,
      and if yes, whether it can be manipulated by training the worker or changing the
      working conditions so as to increase biomechanical variation without jeopardizing
      production. The review concludes that motor variability is, indeed, a relevant
      issue in occupational health and performance and suggests a number of key issues
      for further research.

PMID- 22954429
TI  - What is the most promising treatment for Parkinson's disease: genes, cells,
      growth factors or none of the above?

PMID- 22954430
TI  - Is it possible to transform cardiac scar tissue into beating heart muscle in
      humans?

PMID- 22954431
TI  - Towards photoreceptor transplantation for visual recovery.

PMID- 22954432
TI  - Skin-credible: skin cells used to generate neurons damaged by Parkinson's
      disease.

PMID- 22954434
TI  - Macrophages mediate mesenchymal stem cell efficacy in healing wounds in the aged.

PMID- 22954435
TI  - Trends in the stem cell and regenerative medicine industry.
AB  - The World Stem Cell Regenerative Medicine Congress series, now in its 7th year,
      is organized annually in the USA, Europe and Asia by Terrapinn, a business media
      company with its head office in London, and has grown over the last several years
      into the largest and probably the most important strategic stem cell conference
      where regulators, investors, big pharma, and small and medium enterprises gather
      to share and create synergy in developing and commercializing stem cell
      applications. The conference, held in London on 21-23 May 2012, only confirmed
      that this series is the meeting to attend if you want to get a clear
      understanding of trends in the stem cell and regenerative medicine industry.

PMID- 22954428
TI  - The perineuronal net component of the extracellular matrix in plasticity and
      epilepsy.
AB  - During development the extracellular matrix (ECM) of the central nervous system
      (CNS) facilitates proliferation, migration, and synaptogenesis. In the mature
      nervous system due to changes in the ECM it provides structural stability and
      impedes proliferation, migration, and synaptogensis. The perineuronal net (PN) is
      a specialized ECM structure found primarily surrounding inhibitory interneurons
      where it forms a mesh-like structure around points of synaptic contact. The PN
      organizes the extracellular space by binding multiple components of the ECM and
      bringing them into close proximity to the cell membrane, forming dense aggregates
      surrounding synapses. The PN is expressed late in postnatal development when the
      nervous system is in the final stages of maturation and the critical periods are
      closing. Once fully expressed the PN envelopes synapses and leads to decreased
      plasticity and increases synaptic stability in the CNS. Disruptions in the PN
      have been studied in a number of disease states including epilepsy. Epilepsy is
      one of the most common neurologic disorders characterized by excessive neuronal
      activity which results in recurrent spontaneous seizures. A shift in the delicate
      balance between excitation and inhibition is believed to be one of the underlying
      mechanisms in the development of epilepsy. During epileptogenesis, the brain
      undergoes numerous changes including synaptic rearrangement and axonal sprouting,
      which require structural plasticity. Because of the PNs location around
      inhibitory cells and its role in limiting plasticity, the PN is an important
      candidate for altering the progression of epilepsy. In this review, an overview
      of the ECM and PN in the CNS will be presented with special emphasis on potential
      roles in epileptogenesis.

PMID- 22954436
TI  - Aligned nanofibrillar collagen regulates endothelial organization and migration.
AB  - AIM: Modulating endothelial cell (EC) morphology and motility, with the aim to
      influence their biology, might be beneficial for the treatment of vascular
      disease. We examined the effect of nanoscale matrix anisotropy on EC organization
      and migration for vascular tissue engineering applications. MATERIALS & METHODS:
      We developed a flow processing technique to generate anisotropic nanofibrillar
      collagen. Human ECs were cultured on aligned or on randomly oriented collagen,
      and their cellular alignment and cytoskeletal organization were characterized by
      immunofluorescence staining and time-lapse microscopy. RESULTS: ECs were
      elongated along the direction of aligned collagen nanofibrils and had organized
      focal adhesions. Cellular protrusion migrated with greater directionality and
      higher velocity along the anisotropic nanofibrils compared with cells on random
      nanofibrils. The flow technique can be adapted to fabricate vascular grafts that
      support the endothelial phenotype. CONCLUSION: Aligned nanofibrillar collagen
      regulates EC organization and migration, which can significantly contribute to
      the development of vascular grafts.

PMID- 22954438
TI  - Hypoxic culture of human pluripotent stem cell lines is permissible using mouse
      embryonic fibroblasts.
AB  - AIM: Hypoxia is used within in vitro stem cell culture to recreate conditions
      similar to the in vivo environment surrounding the early blastocyst, from which
      embryonic stem cells can be isolated. Traditionally, basic research has used a
      coculture feeder system to culture pluripotent stem cells; however, it is
      possible that lowered oxygen may restrict cellular metabolic activity of the
      inactivated mouse embryonic fibroblasts (iMEFs) by disrupting oxygen-dependent
      pathways, such as ATP production through aerobic respiration. In this work, we
      examined the potential to continue using routine culture methods, such as iMEFs,
      to support human pluripotent cell expansion under hypoxia instead of feeder-free
      methods that can cause cell instability and offer a poor cell attachment rate.
      MATERIALS & METHODS: Metabolic activity and viability studies were carried out in
      normoxic and hypoxic conditions. Pluripotent stem cells were introduced into
      hypoxia on iMEFs and the rate of colony expansion was compared with normoxic
      conditions. In addition, pluripotent stem cells were grown in hypoxia for over 6
      months to demonstrate maintenance of pluripotency. Immunocytochemistry and
      western blotting evaluated the activity of the hypoxic transcription factor,
      HIF1A. RESULTS: Hypoxia does not significantly affect viability or metabolic
      activity of feeder cells, and there is no detrimental effect on the rate of
      pluripotent stem cell colony expansion when cells are cultured in hypoxia. In
      addition, hypoxic pluripotent stem cells maintain their pluripotent nature and
      ability to differentiate into the three germ layers. CONCLUSION: The traditional
      iMEF coculture method is suitable for use in hypoxia and does not need to be
      replaced with feeder-free systems for hypoxic culture of human pluripotent stem
      cell lines in basic research.

PMID- 22954437
TI  - Generation of human inner ear prosensory-like cells via epithelial-to-mesenchymal
      transition.
AB  - AIM: To identify human hair cell progenitors from adult inner ear sensory
      epithelium. MATERIALS & METHODS: We collected discarded utricles from
      translabyrinthine surgery and isolated human utricular sensory epithelial cells
      (HUCs) to explore whether they can proliferate and obtain features of
      stem/progenitor cells in vitro using reverse transcription PCR and
      immunofluorescence. RESULTS: When cultured in vitro, HUCs expressed genes and
      proteins that are usually present in prosensory cells and stem cells.
      Additionally, dissociated HUCs expanded on the substrates and presented
      properties of mesenchymal cells via epithelial-to-mesenchymal transition.
      CONCLUSION: The results reveal that sensory epithelial cells from the adult human
      inner ear can re-enter the cell cycle and adopt a stem/progenitor cell fate. The
      outcomes of this study may open avenues for human hair cell progenitor
      generation, which could potentially provide a novel stem cell-based replacement
      for hearing loss and other inner ear disorders.

PMID- 22954439
TI  - From cell culture to a cure: pancreatic beta-cell replacement strategies for
      diabetes mellitus.
AB  - Numerous advances have been made in pancreatic beta-cell replacement therapies
      for diabetes mellitus. While these therapies provide a positive impact and
      possible cure for the individual recipient, access is limited by availability of
      donor tissues. The derivation of pluripotent stem cells using efficient
      differentiation technologies has resulted in the generation of insulin-producing
      cells with characteristics similar to islet beta-cells. Experimental
      transplantation studies have shown that these cells are capable of reducing
      hyperglycemia in short-term assays. Novel methodologies that facilitate the
      neogenesis of beta-cells from endogenous hepatic or pancreatic tissue sources are
      also being investigated as a beta-cell replacement strategy. Further research is
      necessary to protect these transplanted or regenerated cells from diabetic
      autoimmune pathology.

PMID- 22954440
TI  - Cardiac repair and restoration using human embryonic stem cells.
AB  - Advances in directed differentiation of human embryonic stem cells (hESCs) toward
      cardiac lineages have generated much interest within the myocardial therapy
      field. Beyond the promise that hESCs would provide a supply of new cardiomyocytes
      to the damaged heart, recent studies have also shown that paracrine effects of
      stem cell therapy may facilitate myocardial healing. This review describes the
      advantages of hESCs for these purposes, current methods for directing
      differentiation of hESCs toward cardiac fates, approaches to purification and
      engineered selection of hESC-derived cardiomyocytes and cardiac precursors, as
      well as animal studies that have shed light on the therapeutic uses of hESCs in
      cardiac regenerative medicine.

PMID- 22954441
TI  - Assessing commercial opportunities for autologous and allogeneic cell-based
      products.
AB  - The two primary cell sources used to produce cell-based therapies are autologous
      (self-derived) and allogeneic (derived from a donor). This analysis attempts to
      compare and contrast the two approaches in order to understand whether there is
      an emerging preference in the market. While the current clinical trials underway
      are slightly biased to autologous approaches, it is clear that both cell-based
      approaches are being aggressively pursued. This analysis also breaks down the
      commercial advantages of each cell-based approach, comparing both cost of goods
      and the ideal indication type for each. While allogeneic therapies have
      considerable advantages over autologous therapies, they do have a distinct
      disadvantage regarding potential immunogenicity. The introduction of the hybrid
      autologous business model provides the ability for autologous-based therapies to
      mitigate some of the advantages that allogeneic cell-based therapies enjoy,
      including cost of goods. Finally, two case studies are presented that demonstrate
      that there is sufficient space for both autologous and allogeneic cell-based
      therapies within a single disease area.

PMID- 22954443
TI  - Tuning kinetics to control droplet shapes on chemically striped patterned
      surfaces.
AB  - The typically elongated shape of droplets on chemically microstriped surfaces has
      been suggested to depend strongly on the kinetics during deposition. Here, we
      unequivocally establish the importance of impact kinetics by comparing the
      geometry of pico- to microliter droplets deposited from an inkjet nozzle with
      those obtained by conventional deposition from a syringe. For large Weber
      numbers, the strongly enhanced spreading during the impact in combination with
      direction-dependent pinning of the contact line gives rise to more spherical
      droplets with a low aspect ratio. The impact energy can be minimized by the
      prolonged firing of small picoliter droplets to form larger droplets or, as shown
      in the past, by using high-viscosity liquids. In the first case, the impact
      energy is absorbed by the liquid already present, therewith reducing the impact
      diameter and consequently forming markedly more elongated droplets.

PMID- 22954445
TI  - Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with
      neuroprotective effects.
AB  - Double emulsion has been used most often in formulation of hydrophilic drugs by
      nanoparticles of biodegradable polymers, which has disadvantages such as low drug
      loading and low drug encapsulation efficiency due to the drug loss in the
      process. The drug release may be too fast for sustained chemotherapy. We
      developed in this research a D-alpha-tocopheryl polyethylene glycol 1000
      succinate (TPGS) prodrug micelle system with cisplatin as a model hydrophilic
      drug. We demonstrated that such a system can successfully deliver the model
      hydrophilic drug with a low critical micelle concentration (CMC) of only 5.01
      mg/L, a high drug load of 4.95% (w/w) and a pH-responsive drug release kinetics
      and higher cellular uptake in comparison with the original drug and the TPGS
      cisplatin prodrug itself. The cell viability experiment showed great enhancement
      of the cisplatin chemotherapy, which is demonstrated by the IC50 value reduced
      from 3.95, 0.98, 0.19 for cisplatin to 1.36, 0.51, 0.08 MUg/mL for the TPGS
      prodrug micelle formulation after 24, 48, 72 h culture with the HepG2
      hepatocarcinoma cells, respectively. Furthermore, such a TPGS prodrug micellar
      formulation showed significant neuroprotective effects for the cisplatin
      chemotherapy, which is demonstrated by the greatly increased IC50 value for the
      SH-SY5Y neuroblast-like cells in comparison between cisplatin and the TPGS
      prodrug micelle formulation. The TPGS prodrug micelles can also be generalized to
      become a new strategy for codelivery of hydrophilic and hydrophobic drugs and/or
      imaging agents.

PMID- 22954446
TI  - Identification and characterization of four process-related impurities in
      retigabine.
AB  - HPLC analysis of retigabine, a novel antiepileptic drug revealed four previously
      unknown impurities. These were identified by liquid chromatography-tandem mass
      spectrometry using electrospray ionization and quadrupole time-of-flight mass
      analyzer. Further, the structures of the impurities were confirmed by synthesis
      followed by characterization by mass spectrometry, nuclear magnetic resonance
      spectroscopy, infrared spectroscopy, and chromatographic retention time profile
      analysis. On the basis of these data and knowledge of the synthetic scheme of
      retigabine, the four impurities were identified as ethyl 2,4
      diaminophenylcarbamate (Imp-1), ethyl 2-amino-4-(benzylamino)phenylcarbamate (Imp
      2), ethyl 2-acetamido-4-(4-fluorobenzylamino)phenylcarbamate (Imp-3), and ethyl 4
      (4-fluorobenzylamino)-2-nitrophenylcarbamate (Imp-4). The possible mechanisms by
      which these impurities were formed are also discussed.

PMID- 22954444
TI  - Comparison of the cutaneous iontophoretic delivery of rasagiline and selegiline
      across porcine and human skin in vitro.
AB  - The objective was to investigate the anodal iontophoresis of the MAO-B inhibitors
      rasagiline (RAS) and selegiline (SEL) across porcine and human skin in vitro.
      Passive delivery of RAS and SEL from aqueous solution was minimal; however,
      increasing current density from 0.1 to 0.3 and 0.5 mA/cm(2) produced a linear
      increase in steady-state iontophoretic flux (J(ss,RAS)=49.1i(d)+27.9 (r(2)=0.96)
      and J(ss,SEL)=27.8i(d)+25.8 (r(2)=0.98)). In the absence of background
      electrolyte, a four-fold change in donor concentration (10, 20 and 40 mM) did not
      produce a statistically significant increase in cumulative permeation of either
      drug after iontophoresis at 0.5mA/cm(2) for 7h. Co-iontophoresis of acetaminophen
      confirmed that electromigration was the dominant transport mechanism for both
      drugs (~90%). Total iontophoretic delivery of RAS and SEL across porcine and
      human skin in vitro was statistically equivalent (RAS: 1512.7 +/- 163.7 and
      1523.6 +/- 195.9 MUg/cm(2), respectively, and SEL: 1268.7 +/- 231.2 and 1298.3 +/
      253.3 MUg/cm(2), respectively). Transport efficiencies for RAS and SEL were good
      (ranged from 6.81 to 8.50 and 2.86 to 3.61%, respectively). Furthermore, the
      delivery efficiency, i.e., the fraction of the drug in the formulation that was
      delivered was very high (>56% at 0.5 mA/cm(2)). Cumulative permeation of RAS and
      SEL from carbopol gels, potential drug reservoirs for iontophoretic systems, was
      891.5 +/- 148.3 and 626.6 +/- 162.4 MUg/cm(2), respectively; this was less than
      from solution and was tentatively attributed to either different partitioning or
      slower drug diffusion in the gel matrix. The results demonstrated that
      therapeutic amounts of rasagiline and selegiline could be easily delivered by
      transdermal iontophoresis with simple gel patches of modest surface area.

PMID- 22954447
TI  - Phospholipids covalently attached to silica particles as stationary phase in nano
      liquid chromatography.
AB  - Silica particles were covalently modified with phospholipids and used as packing
      material for nano-liquid chromatography (nano-LC). This modification involved
      aminopropylsilylation of the raw silica particles using 3-(aminopropyl)
      triethoxysilane, covalent binding of glutaraldehyde molecules to the
      aminopropylsilylated particles, and finally covalent binding of different
      phospholipid vesicles containing primary amino groups to the iminoaldehyde silica
      particles. Capillaries with an inner diameter of 100MUm were packed with
      phospholipid-coated silica particles using a slurry packing method. The packed
      capillaries were tested in nano-LC with UV-detection for the separation of
      acidic, neutral, and basic model analytes. The effect of the buffer ion on the
      retention factor of the analytes was evaluated using buffer solutions with
      constant ionic strength and pH. In addition, the effect of the volume of methanol
      in the mobile phase was studied. The calculated distribution coefficients
      (logK(D)) of the model compounds were in agreement with those reported in the
      literature. A good correlation between logK(D) values and octanol/water
      partitioning coefficients (P(o/w)) for neutral hydrophobic analytes was obtained
      proving the applicability of the method for predicting partitioning of the
      compounds with the biomembranes.

PMID- 22954448
TI  - A full validated hydrophilic interaction liquid chromatography-tandem mass
      spectrometric method for the quantification of oxaliplatin in human plasma
      ultrafiltrates.
AB  - Oxaliplatin is a platinum agent that is used for treatment of colorectal cancer.
      A sensitive and selective hydrophilic interaction liquid chromatography-tandem
      mass spectrometric method for the quantification of oxaliplatin was developed.
      Human plasma ultrafiltrates were precipitated by acetonitrile containing
      carboplatin as an internal standard and further diluted with acetonitrile.
      Chromatographic separation of oxaliplatin and the internal standard was achieved
      with a column modified with phosphorylcholine and an isocratic mobile phase
      (acetonitrile/water/acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min.
      The lower limit of quantification for oxaliplatin was 25ng/mL. The linearity
      range of the method was from 25 to 5000ng/mL. The intra-day precision and inter
      day precision (RSD) ranged from 0.8 to 6.1%, and the accuracy (RE) was within +/
      4.5%. The extraction recoveries from human plasma ultrafiltrates were 83.6-91.6%,
      and ion suppression caused by matrix components was 86.7-88.5% at three different
      levels, respectively. This method was applied to a clinical pharmacokinetic study
      of oxaliplatin in a cancer patient. The maximum concentration of colorectal
      cancer patient administered oxaliplatin was 1650ng/mL.

PMID- 22954449
TI  - Qualitative and quantitative assessment of marketed erythropoiesis-stimulating
      agents by capillary electrophoresis.
AB  - Formulated erythropoiesis stimulating agents (ESAs) containing erythropoietin
      (EPO)-alpha, EPO-beta or darbepoetin-alpha were analyzed by capillary
      electrophoresis with a previously published method requiring no sample pre
      treatment [1]. In this study, the method proved to be applicable to all
      formulations encountered, that is, in the presence of polysorbate 80, polysorbate
      20 or human serum albumin as major excipients, thus extending the range of
      products that can be analyzed without pre-treatment. Method performance was
      evaluated and showed good linearity, range, precision and sensitivity. No
      significant matrix effects were observed for the various formulations. The
      ability of the method to resolve isoforms of each of the three active ingredients
      enabled comparison of the isoform distribution of finished products with that of
      the respective drug substance. In general, finished products and their
      corresponding drug substances showed similar isoform distribution and all were
      within manufacturer specifications. In addition, the content in active ingredient
      in the various dosage strengths was found to be in close agreement with the label
      claims with the exception of 2 out of 131 containers analyzed. Overall, this
      study demonstrated that the capillary zone electrophoresis method could be
      successfully applied to the analysis of most of the ESA products currently on the
      market in North America and Europe and that all products were found to have good
      batch-to-batch consistency.

PMID- 22954450
TI  - Comment on the review article "Thermostatted kinetic equations as models for
      complex systems in physics and life sciences" by Carlo Bianca.

PMID- 22954452
TI  - Peptide chemistry.

PMID- 22954451
TI  - Empirical evaluation of humpback whale telomere length estimates; quality control
      and factors causing variability in the singleplex and multiplex qPCR methods.
AB  - BACKGROUND: Telomeres, the protective cap of chromosomes, have emerged as
      powerful markers of biological age and life history in model and non-model
      species. The qPCR method for telomere length estimation is one of the most common
      methods for telomere length estimation, but has received recent critique for
      being too error-prone and yielding unreliable results. This critique coincides
      with an increasing awareness of the potentials and limitations of the qPCR
      technique in general and the proposal of a general set of guidelines (MIQE) for
      standardization of experimental, analytical, and reporting steps of qPCR. In
      order to evaluate the utility of the qPCR method for telomere length estimation
      in non-model species, we carried out four different qPCR assays directed at
      humpback whale telomeres, and subsequently performed a rigorous quality control
      to evaluate the performance of each assay. RESULTS: Performance differed
      substantially among assays and only one assay was found useful for telomere
      length estimation in humpback whales. The most notable factors causing these
      inter-assay differences were primer design and choice of using singleplex or
      multiplex assays. Inferred amplification efficiencies differed by up to 40%
      depending on assay and quantification method, however this variation only
      affected telomere length estimates in the worst performing assays. CONCLUSION:
      Our results suggest that seemingly well performing qPCR assays may contain biases
      that will only be detected by extensive quality control. Moreover, we show that
      the qPCR method for telomere length estimation can be highly precise and
      accurate, and thus suitable for telomere measurement in non-model species, if
      effort is devoted to optimization at all experimental and analytical steps. We
      conclude by highlighting a set of quality controls which may serve for further
      standardization of the qPCR method for telomere length estimation, and discuss
      some of the factors that may cause variation in qPCR experiments.

PMID- 22954453
TI  - The characteristics, functions and inhibitors of three aminopeptidases belonging
      to the m1 family.
AB  - Various aminopeptidases belong to the M1 aminopeptidase family. They are all zinc
      dependent enzymes playing important roles in several biological processes such as
      regulation of blood pressure under both physiological and pathological
      conditions, and the angiogenesis and metastasis of tumor, etc. They all have the
      highly conserved HEXXH(X)18E zinc-binding and GAMEN motifs essential for enzyme
      activities. In this review, the current situation regarding the biochemical
      characteristics, biological functions and inhibitors of three important members
      of these enzymes, aminopeptidase A, aminopeptidase N and aminopeptidase B are
      summarized.

PMID- 22954455
TI  - Indoor air pollutants in office environments: assessment of comfort, health, and
      performance.
AB  - Concentrations of volatile organic compounds (VOCs) in office environments are
      generally too low to cause sensory irritation in the eyes and airways on the
      basis of estimated thresholds for sensory irritation. Furthermore, effects in the
      lungs, e.g. inflammatory effects, have not been substantiated at indoor relevant
      concentrations. Some VOCs, including formaldehyde, in combination may under
      certain environmental and occupational conditions result in reported sensory
      irritation. The odour thresholds of several VOCs are low enough to influence the
      perceived air quality that result in a number of acute effects from reported
      sensory irritation in eyes and airways and deterioration of performance. The
      odour perception (air quality) depends on a number of factors that may influence
      the odour impact. There is neither clear indication that office dust particles
      may cause sensory effects, even not particles spiked with glucans, aldehydes or
      phthalates, nor lung effects; some inflammatory effects may be observed among
      asthmatics. Ozone-initiated terpene reaction products may be of concern in ozone
      enriched environments (>=0.1mg/m(3)) and elevated limonene concentrations, partly
      due to the production of formaldehyde. Ambient particles may cause cardio
      pulmonary effects, especially in susceptible people (e.g. elderly and sick
      people); even, short-term effects, e.g. from traffic emission and candle smoke
      may possibly have modulating and delayed effects on the heart, but otherwise
      adverse effects in the airways and lung functions have not been observed.
      Secondary organic aerosols generated in indoor ozone-initiated terpene reactions
      appear not to cause adverse effects in the airways; rather the gaseous products
      are relevant. Combined exposure to particles and ozone may evoke effects in
      subgroups of asthmatics. Based on an analysis of thresholds for odour and sensory
      irritation selected compounds are recommended for measurements to assess the
      indoor air quality and to minimize reports of irritation symptoms, deteriorated
      performance, and cardiovascular and pulmonary effects.

PMID- 22954454
TI  - Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy
      and radiotherapy.
AB  - High expression of autotaxin in cancers is often associated with increased tumor
      progression, angiogenesis and metastasis. This is explained mainly since
      autotaxin produces the lipid growth factor, lysophosphatidate (LPA), which
      stimulates cell division, survival and migration. It has recently become evident
      that these signaling effects of LPA also produce resistance to chemotherapy and
      radiation-induced cell death. This results especially from the stimulation of
      LPA(2) receptors, which depletes the cell of Siva-1, a pro-apoptotic signaling
      protein and stimulates prosurvival kinase pathways through a mechanism mediated
      via TRIP-6. LPA signaling also increases the formation of sphingosine 1
      phosphate, a pro-survival lipid. At the same time, LPA decreases the accumulation
      of ceramides, which are used in radiation therapy and by many chemotherapeutic
      agents to stimulate apoptosis. The signaling actions of extracellular LPA are
      terminated by its dephosphorylation by a family of lipid phosphate phosphatases
      (LPP) that act as ecto-enzymes. In addition, lipid phosphate phoshatase-1
      attenuates signaling downstream of the activation of both LPA receptors and
      receptor tyrosine kinases. This makes many cancer cells hypersensitive to the
      action of various growth factors since they often express low LPP1/3 activity.
      Increasing our understanding of the complicated signaling pathways that are used
      by LPA to stimulate cell survival should identify new therapeutic targets that
      can be exploited to increase the efficacy of chemo- and radio-therapy. This
      article is part of a Special Issue entitled Advances in Lysophospholipid
      Research.

PMID- 22954456
TI  - The longitudinal relationship between thigh muscle mass and the development of
      knee osteoarthritis.
AB  - OBJECTIVE: Greater quadriceps strength has been found to reduce risk for
      symptomatic knee osteoarthritis (SxKOA) and knee joint space narrowing (JSN).
      However, this finding could relate to muscle mass or activation pattern. The
      purpose of this study was to assess whether greater thigh muscle mass protects
      against (1) incident radiographic (RKOA), (2) incident SxKOA or (3) worsening of
      knee JSN by 30-month follow-up. DESIGN: Multicenter Osteoarthritis (MOST) study
      participants, who underwent dual-energy X-ray absorptiometry (DXA) at the Iowa
      site were included. Thigh muscle mass was calculated from DXA image sub-regions.
      Sex-stratified, knee-based analyses controlled for incomplete independence
      between limbs within subjects. The effect of thigh lean mass and specific
      strength as predictors of ipsilateral RKOA, SxKOA and worsening of JSN were
      assessed, while controlling for age, body mass index (BMI), and history of knee
      surgery. RESULTS: A total of 519 men (948 knees) and 784 women (1453 knees) were
      included. Mean age and BMI were 62 years and 30 kg/m(2). Thigh muscle mass was
      not associated with risk for RKOA, SxKOA or knee JSN. However, in comparison with
      the lowest tertile, those in the highest and middle tertiles of knee extensor
      specific strength had a lower risk for SxKOA and JSN [odds ratio (OR) 0.29-0.68].
      CONCLUSIONS: Thigh muscle mass does not appear to confer protection against
      incident or worsening knee OA. These findings suggest that future studies of risk
      for knee OA should focus on the roles of knee extensor neuromuscular activation
      and muscle physiology, rather than the muscle mass.

PMID- 22954457
TI  - Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to
      mechanical stress.
AB  - OBJECTIVE: The p53 tumor-suppressor protein p53R2 is activated in response to
      various stressors that act on cell signaling. When DNA is damaged,
      phosphorylation of p53 at its Ser 15 residue induces p53R2 production. The role
      of p53R2 in chondrocytes remains poorly understood. In this study, we evaluated
      in chondrocytes, p53R2 expression and its regulation in response to mechanical
      stress. Furthermore, we investigated the function of p53R2 in relation to
      mechanotransduction. METHODS: Osteoarthritis (OA) cartilage obtained from total
      knee replacements and normal cartilage obtained from femoral neck fractures was
      used to measure p53R2 expression by using immunohistochemistry, western blotting,
      and real-time polymerase chain reaction (PCR). The OA chondrocytes were subjected
      to a high magnitude of cyclical tensile strain by using an FX-2000 Flexercell
      system. Next, sulfated glycosaminoglycan (sGAG) production was quantified in
      these cells. Protein expression of p53R2, and phosphorylation of Akt, p38MAPK,
      ERK1/2, and JNK was also detected using western blotting. Moreover, Akt
      phosphorylation was detected after transfecting the cells with p53R2-specific
      small interfering RNA (siRNA). RESULTS: Expression of p53R2 was significantly
      increased in OA chondrocytes and in chondrocytes after applying 5% tensile strain
      to the cells. However, Akt phosphorylation was down-regulated in OA chondrocytes
      after the strain, and was up-regulated after transfection of p53R2. sGAG protein
      as well as collagen type II and aggrecan mRNA was increased following
      transfection of p53R2-specific siRNA after 5% tensile strain. CONCLUSIONS: p53R2
      could regulate matrix synthesis via Akt phosphorylation during chondrocyte
      mechanotransduction. Down-regulation of p53R2 may be a new therapeutic approach
      in OA therapy.

PMID- 22954458
TI  - Cardiovascular risk factors predict survival in middle-aged men during 50 years.
AB  - OBJECTIVES: We aimed at studying the expectancy of life in middle-aged men as a
      function of several personal characteristics and risk factors. MATERIAL AND
      METHODS: A sample of 1712 Italian men aged 40-59, first examined in 1960, was
      followed-up for mortality for 50 years. The length of survival was estimated as a
      function of 48 personal characteristics and risk factors using the multiple
      linear regression. RESULTS: In 50 years 1672 men died (97.7%) and 40 survived
      (2.3%). Twenty risk factors, most of which were never measured in previous
      studies of such duration, proved to be significant, for the estimation of
      survival with an overall adjusted R(2) of 0.3236. They were: age, 4
      anthropometric measurements (body mass index, and its squared term, laterality
      linearity index, shoulder/pelvis shape), mean blood pressure, father and mother
      history of premature (<65-year) death, marital status, arm circumference, 2
      respiratory measurements (vital capacity and forced expiratory volume), serum
      cholesterol, corneal arcus, xantelasma, cancer, cardiovascular diseases, diabetes
      and chronic bronchitis. Coefficients of 5 suitable risk factors became definitely
      larger after adjustment for regression dilution bias with 5 year data. All 40
      cases of survival were located in the higher 5 deciles of estimated survival and
      25 (62.5%) were in the upper decile. CONCLUSION: A small number of risk factors
      and personal characteristics, mainly known as cardiovascular risk factors and
      measured once in middle-aged men, are strongly associated with the length of
      survival in a 50-year follow-up.

PMID- 22954459
TI  - Comparison of two internet-based interventions for problem drinkers: randomized
      controlled trial.
AB  - BACKGROUND: Alcohol problems are a serious public health concern, and few problem
      drinkers ever seek treatment. The Internet is one means of promoting access to
      care, but more research is needed to test the best types of interventions to
      employ. Evaluation of Internet-based interventions that contain a variety of
      research-validated cognitive-behavioral tools, which have been shown to be
      helpful to those with more severe alcohol concerns, should be a priority.
      OBJECTIVE: To evaluate whether providing access to an extended Internet
      intervention for alcohol problems offers additional benefits in promoting
      reductions in alcohol consumption compared with a brief Internet intervention.
      The hypothesis for the current trial was that respondents who were provided with
      access to an extended Internet intervention (the Alcohol Help Center [AHC]) would
      display significantly improved drinking outcomes at 6-month follow-up, compared
      with respondents who were provided with access to a brief Internet intervention
      (the Check Your Drinking [CYD] screener). METHODS: A single-blinded randomized
      controlled trial with a 6-month follow-up. A general population sample of problem
      drinkers was recruited through newspaper advertisements in a large metropolitan
      city. Baseline and follow-up data were collected by postal mail. RESULTS: A
      volunteer sample of problem drinkers of legal drinking age with home access to
      the Internet were recruited for the trial. Of 239 potential respondents recruited
      in 2010, 170 met inclusion criteria (average age 45 years; 101/170, 59.4% male;
      average Alcohol Use Disorders Identification Test [AUDIT] score of 22). Follow-up
      rates were 90.0% (153/170) with no adverse effects of the interventions reported.
      A repeated-measures multivariate analysis of variance of the outcome measures
      using an intent-to-treat approach found a significantly greater reduction in
      amount of drinking among participants provided access to the AHC than among
      participants provided access to the CYD (P = .046). CONCLUSIONS: The provision of
      the AHC gave additional benefit in the short term to problem drinkers over that
      seen from the research-validated CYD, indicating the benefits of promoting access
      to these interventions as one means of helping people with problem drinking
      concerns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01114919;
      http://clinicaltrials.gov/ct2/show/NCT01114919 (Archived by WebCite at
      http://www.webcitation.org/68t1dCkRZ).

PMID- 22954460
TI  - Diffusive diffraction phenomenon observed by PGSE NMR technique in a sugar-based
      low-molecular-mass gel.
AB  - The paper presents the diffusive diffraction phenomenon observed by the single
      pulse-gradient spin-echo (s-PGSE) NMR technique in a real porous material: a gel
      composed of low-molecular-mass gelator methyl-4,6-O-(p-nitrobenzylidene)-alpha-D
      glucopyranoside and toluene. Thanks to this phenomenon, we can probe the true
      microstructure (not xerogel) in which the toluene diffuses. To analyze the
      measured diffusion-diffraction pattern, we employed a composite bicompartmental
      model that superimposes restricted diffusion in small cavities of the gel matrix
      within the bundles of crossing fibers, with free diffusion in large and
      unconfined compartments between the bundles of crossing fibers. For restricted
      diffusion a pore-hopping formalism was applied. The observation of the
      diffraction pattern and its analysis leads to the conclusion that the pores, in
      the slow diffusing compartment of studied gel are ordered, at least locally, and
      relatively monodisperse with a size of 64 MUm. Moreover, the restricting walls
      formed by the crossing fibers are perpendicular to the direction of the diffusion
      gradient.

PMID- 22954461
TI  - An integrated process and management tools for ranking multiple emerging threats
      to animal health.
AB  - The UK's Department for Environment, Food and Rural Affairs supports the use of
      systematic tools for the prioritisation of known and well defined animal diseases
      to facilitate long and medium term planning of surveillance and disease control
      activities. The recognition that emerging events were not covered by the existing
      disease-specific approaches led to the establishment of the Veterinary Risk Group
      (VRG), constituted of government officials, and supporting structures such as the
      Risk Management Cycle and the Emerging Threat Highlight Report (ETHiR), to
      facilitate the identification, reporting and assessment of emerging threats to
      UK's animal health. Since its inception in November 2009 to the end of February
      2011, the VRG reviewed 111 threats and vulnerabilities (T&V) reported through
      ETHiR. In July 2010 a decision support system (DSS) based on multi-criteria
      decision-analysis (MCDA) improved ETHiR to allow the systematic prioritisation of
      emerging T&V. The DSS allows the regular ranking of emerging T&V by calculating a
      set of measurement indices related to the actual impact, possible impact on
      public perception and level of available capabilities associated with every T&V.
      The systematic characterisation of the processes leading to the assessment of T&V
      by the VRG has led to a consistent, auditable and transparent approach to the
      identification and assessment of emerging risks. The regular use of MCDA to
      manage a portfolio of emerging risks represents a different and novel application
      of MCDA in a health related context.

PMID- 22954462
TI  - The effect of interruptions during training on the time to the first trial and
      race start in Thoroughbred racehorses.
AB  - Few studies have investigated the effect of having interruptions during training
      on future training and racing performance in Thoroughbred racehorses. The aim of
      this paper was to investigate the effect of having an interruption before the
      first trial on starting in a trial or a race. A prospective cohort study was used
      to record the training activity of a cohort of Thoroughbred racehorses, over two
      racing seasons. Fourteen racehorse trainers recorded information on the distances
      worked at canter and at fast speeds (<15s/200 m) and provided reasons for horses
      not training, or for having interruptions (break from training). Trial and racing
      results were obtained from the New Zealand Thoroughbred Racing online database. A
      Cox proportional hazards regression model was used to investigate two outcome
      measures of performance: (1) time to the first trial and (2) time to the first
      race. The type of interruption that had occurred before the first trial was the
      main exposure of interest, and was grouped into: no interruption, voluntary (no
      known condition or disease present) and involuntary interruptions (due to the
      presence of a condition or disease). A total of 160/200 (80%) horses started in
      at least one trial and 100/205 (48%) horses started in at least one race during
      the study period. The median time to starting in a trial or a race differed
      significantly (p<0.001) with the type of interruption. The hazard of starting in
      a trial was lower for horses experiencing voluntary and involuntary interruptions
      (p<0.001) but there was no association with starting in a race, after adjusting
      for confounding variables. As age at the start of training increased the hazard
      of starting in a trial decreased. Horses accumulating longer distances at 15s/200
      m had a higher hazard of starting in a trial, whilst horses accumulating fewer
      events at high speed and fewer trials had a reduced hazard of starting in a race.
      There was significant clustering at the trainer level for both the outcomes
      investigated. Interruptions to training had an effect on the time to, and hazard
      of, a trial but not a race start. The timing of these interruptions may have
      implications for future racing success and career longevity.

PMID- 22954463
TI  - Interobserver reliability of pulse diagnosis using Traditional Korean Medicine
      for stroke patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the reliability between
      observers with regard to pulse signs that are observed by Traditional Korean
      Medicine (TKM) clinicians. METHODS: A total 658 patients with stroke who were
      admitted into Oriental medical university hospitals from February 2010 through
      December 2010 were included in this study. Each patient was seen independently by
      2 experts from the same department for an examination of the pulse signs.
      Interobserver reliability was measured using three methods: simple percentage
      agreement, the kappa value, and the AC(1) statistic. RESULTS: The kappa value
      indicated that the interobserver reliability in evaluating the pulse signs of the
      subjects ranged from poor to moderate, whereas the AC(1) analysis revealed that
      agreement between the 2 experts was generally high (with the exception of
      slippery pulse). The kappa value indicated that the interobserver reliability for
      assessing subjects who garnered the same opinion between the raters was generally
      moderate to good (with the exceptions of rough pulse and sunken pulse) and that
      the AC(1) measure of agreement between the 2 experts was generally high.
      CONCLUSIONS: Pulse diagnosis is regarded as one of the most important procedures
      in TKM, despite the aforementioned limitations. This study reveals that the
      interobserver reliability in making a pulse diagnosis in stroke patients is not
      particularly high when objectively quantified. Additional research is needed to
      help reduce this lack of reliability for various portions of the pulse diagnosis.

PMID- 22954464
TI  - Adoption in China of Clinical Practice Guidelines for hypertension using
      Traditional Chinese Medical approaches: a literature review based on clinical
      studies.
AB  - BACKGROUND: Increasing Clinical Practice Guidelines (CPGs) of Traditional Chinese
      Medicine (TCM) have been developed in China, and it is not clear about the real
      application in the clinical studies. This study aimed to analyze the adoption of
      CPGs for hypertension using TCM therapy by investigating the clinical research
      literature on representative CPGs for TCM in China. METHODS: All CPGs on TCM for
      hypertension were collected and investigated from all of the clinical research
      literature published in China from January 2005 to December 2010. Ten (10) CPGs
      on TCM for hypertension were searched and analyzed, collecting data about the
      issuing organization, date of publication, classification, characteristics,
      contents, and citation rates. RESULTS: By the end of December 2008, 10 CPGs on
      TCM for hypertension were found. Of these guidelines, one was a Chinese national
      standard, one was a local authority standard, two were professional
      administration standard, and six were academic association standards.
      Furthermore, four were compiled under the title of hypertension based on TCM
      syndrome differentiation and six were only compiled under the title of a TCM
      syndrome. Of all the research articles (n=695), TCM CPGs were cited in 417
      articles (60%). TCM CPGs on hypertension were commonly used as standards for
      diagnosis and/or outcome measurements. Three hundred and seventy-nine (379)
      clinical research articles were unclear or inconsistent in their adoption of TCM
      CPG, accounting for 55% of all clinical articles. Seven (7) categories of
      inconsistent or unclear citations of TCM CPG were identified, and the total
      amount of occurrences of seven categories on inconsistent citation was 572.
      CONCLUSIONS: About 60% publications cited the CPGs for their clinical research,
      and most of them cited in an inconsistent and unclear way. According to the
      result, better training of TCM practitioners and improvement of CPG development
      and adoption are needed.

PMID- 22954465
TI  - Yeasts as important agents of onychomycosis: in vitro activity of propolis
      against yeasts isolated from patients with nail infection.
AB  - OBJECTIVE: The purposes of this study were to determine the frequency of the
      yeast species obtained from patients with clinical features of onychomycosis and
      the in vitro antifungal susceptibility of the yeast species to propolis. METHODS:
      A prospective study was carried out at the Mycology Research Center in Iran from
      2010 to 2011. Clinical diagnosis was performed by direct microscopic examination
      and culture. Different yeast species were identified by morphological and
      biochemical tests. An antifungal susceptibility test to fluconazole (FLU) and
      propolis by the broth microdilution method was performed on each isolate.
      RESULTS: One hundred and twenty-eight fungal isolates were obtained. The most
      prevalent fungi were yeasts (81, 63.2%), dermatophytes (36, 28.1%), and
      nondermatophyte fungi (11, 8.6%). Fingernails were more affected than toenails
      (65.4% vs. 19.8%, respectively). The most frequently found species was Candida
      albicans (38.5%), followed by Candida spp. (23.1%), C. tropicalis (10.8%), C.
      kefyr (6.2%), C. krusei (3.1%), Malassezia globosa (4.6%), M. slooffiae (4.6%),
      and M. pachydermatis (1.5%). Of all yeast isolates (65), seven showed resistance
      to FLU. The average MIC of propolis for FLU-susceptible isolates was 5.8 MUg/mL,
      whereas this value was 12.25 MUg/mL for FLU-resistant isolates. CONCLUSION: Our
      results proved that the propolis inhibits the growth of pathogenic yeasts and
      confirmed the efficiency of propolis as an anti-Candida and anti-Malassezia
      agent.

PMID- 22954466
TI  - Danger, intracellular signaling, and the orchestration of dendritic cell function
      in skin sensitization.
AB  - Allergic contact dermatitis is an important occupational and environmental
      disease caused by topical exposure to chemical allergens. An area of considerable
      interest and, in the context of hazard identification and characterization, an
      area of great importance is developing an understanding of the characteristics
      that confer on chemicals the ability to cause skin sensitization. For the
      successful acquisition of skin sensitization, it is necessary that a chemical
      must gain access to the viable epidermis, form stable immunogenic associations
      with host proteins, and provide the necessary stimuli for the activation,
      mobilization, and maturation of skin dendritic cells (DC). It is the last of
      these properties that is the subject of this article. The purpose here is to
      review the mechanisms through which skin sensitizers provide the triggers
      necessary for engagement of cutaneous DC. Of particular interest are the nature
      and function of danger signals elicited by skin sensitizing chemicals. Among the
      pathways considered here are those involving Toll-like receptors, C-type lectin
      receptors, neuropeptide receptors, prostanoid receptors, and the inflammasome.
      Collectively, danger signals in the skin provide a bridge between the innate and
      adaptive immune systems and are of pivotal importance for the initiation of
      cutaneous immune responses, including those to chemical allergens that result in
      skin sensitization. 

PMID- 22954467
TI  - Moving beyond walkability: on the potential of health geography.
AB  - In the context of the substantial volume of research focused in recent years on
      the walkability of the built environment, this report presents some initial
      thoughts on what the sub-discipline of health geography might be able to
      contribute, beyond what it currently does, to existing debates. It is posited
      that at one level this contribution could be critical yet constructive, focussing
      on the limitations of current epistemological and methodological approaches but
      offering ideas on how they and others might be developed. At another level, given
      the limited scope of existing walkability research, a further contribution could
      be to pay attention to different forms of embodiment, movement activities, their
      relationships to health, and the places, experiences, agency and cultures
      involved.

PMID- 22954468
TI  - Increase in the coordination number of a cobalt porphyrin after photo-induced
      interfacial electron transfer into nanocrystalline TiO2.
AB  - Spectroscopic, electrochemical, and kinetic data provide compelling evidence for
      a coordination number increase initiated by interfacial electron transfer. Light
      excitation of Co(I)(meso-5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin) anchored
      to a nanocrystalline TiO(2) thin film, abbreviated Co(I)P/TiO(2), immersed in an
      acetonitrile:pyridine electrolyte resulted in rapid excited state injection,
      k(inj) > 10(8) s(-1), to yield Co(II)P/TiO(2)(e(-)), followed by axial
      coordination of pyridine to the Co(II)P and hence an increase in coordination
      number from four to five. The formal oxidation state and coordination environment
      of the Co metalloporphyrin on TiO(2) were assigned through comparative studies in
      fluid solution as well as by comparisons to previously reported data. The
      kinetics for pyridine coordination were successfully modeled with a pseudo-first
      order kinetic model that yielded a second-order rate constant of k(+py) = 2 *
      10(8) M(-1) s(-1). Spectro-electrochemical measurements showed that pyridine
      coordination resulted in a ~200 mV negative shift in the Co(II/I) reduction
      potential, E degrees (Co(II/I)/TiO(2)) = -0.72 V and E degrees
      (Co(II/I)(py)/TiO(2)) = -0.85 V vs NHE. With some assumptions, this indicated an
      equilibrium formation constant K(f) = 400 M(-1) for the Co(II)P(py)/TiO(2)
      compound. The kinetics for charge recombination were non-exponential under all
      conditions studied, but were successfully modeled by the Kohlrausch-Williams
      Watts (KWW) function with observed rate constants that decreased by about a
      factor of 100 when pyridine was present. The possible mechanisms for charge
      recombination are discussed.

PMID- 22954469
TI  - Stochastic cellular automata model of cell migration, proliferation and
      differentiation: validation with in vitro cultures of muscle satellite cells.
AB  - Cell migration and proliferation has been modelled in the literature as a process
      similar to diffusion. However, using diffusion models to simulate the
      proliferation and migration of cells tends to create a homogeneous distribution
      in the cell density that does not correlate to empirical observations. In fact,
      the mechanism of cell dispersal is not diffusion. Cells disperse by crawling or
      proliferation, or are transported in a moving fluid. The use of cellular
      automata, particle models or cell-based models can overcome this limitation. This
      paper presents a stochastic cellular automata model to simulate the
      proliferation, migration and differentiation of cells. These processes are
      considered as completely stochastic as well as discrete. The model developed was
      applied to predict the behaviour of in vitro cell cultures performed with adult
      muscle satellite cells. Moreover, non homogeneous distribution of cells has been
      observed inside the culture well and, using the above mentioned stochastic
      cellular automata model, we have been able to predict this heterogeneous cell
      distribution and compute accurate quantitative results. Differentiation was also
      incorporated into the computational simulation. The results predicted the myotube
      formation that typically occurs with adult muscle satellite cells. In conclusion,
      we have shown how a stochastic cellular automata model can be implemented and is
      capable of reproducing the in vitro behaviour of adult muscle satellite cells.

PMID- 22954470
TI  - Loss of aminoglycoside sensitivity in HEI-OC1 cells?

PMID- 22954471
TI  - Low baseline startle in anorexia nervosa patients.
AB  - This study examined baseline startle magnitude, using eye blink response and skin
      conductance response in anorexia nervosa patients. Twenty female in-patients with
      anorexia nervosa and an equal number of female healthy controls were tested.
      Baseline startle response was assessed during blank screens while four startling
      loud sounds (a 116 dB, 1s, 250 Hz tone) were delivered with a time interval
      ranging from 35 to 55 s. It was investigated if BMI and state anxiety correlated
      with physiological responses. The clinical sample showed a lower baseline startle
      reflex measured with both indices, than healthy controls. Across the whole
      sample, a single regression model partially explained the relationship between
      BMI and baseline skin conductance response.

PMID- 22954474
TI  - Reproductive history patterns and long-term mortality rates: a Danish, population
      based record linkage study.
AB  - BACKGROUND: Inconsistent definitions and incomplete data have left society
      largely in the dark regarding mortality risks generally associated with pregnancy
      and with particular outcomes, immediately after resolution and over the long
      term. Population-based record-linkage studies provide an accurate means for
      deriving maternal mortality rate data. METHOD: In this Danish population-based
      study, records of women born between 1962 and 1993 (n = 1,001,266) were examined
      to identify associations between patterns of pregnancy resolution and mortality
      rates across 25 years. RESULTS: With statistical controls for number of
      pregnancies, birth year and age at last pregnancy, the combination of induced
      abortion(s) and natural loss(es) was associated with more than three times higher
      mortality rate than only birth(s). Moderate risks were identified with only
      induced abortion, only natural loss and having experienced all outcomes compared
      with only birth(s). Risk of death was more than six times greater among women who
      had never been pregnant compared with those who only had birth(s). Increased
      risks of death were 45%, 114% and 191% for 1, 2 and 3 abortions, respectively,
      compared with no abortions after controlling for other reproductive outcomes and
      last pregnancy age. Increased risks of death were equal to 44%, 86% and 150% for
      1, 2 and 3 natural losses, respectively, compared with none after including
      statistical controls. Finally, decreased mortality risks were observed for women
      who had experienced two and three or more births compared with no births.
      CONCLUSION: This study offers a broad perspective on reproductive history and
      mortality rates, with the results indicating a need for further research on
      possible underlying mechanisms.

PMID- 22954475
TI  - Photothermal genetic engineering.
AB  - Optical methods for manipulation of cellular function have enabled deconstruction
      of genetic and neural circuits in vitro and in vivo. Plasmonic gold nanomaterials
      provide an alternative platform for external optical manipulation of genetic
      circuits. The tunable absorption of gold nanoparticles in the infrared spectral
      region and straightforward surface functionalization has led to applications in
      intracellular delivery and photorelease of short RNAs, recently enabling
      bidirectional photothermal modulation of specific genes via RNA interference
      (RNAi). We discuss recent advances in optical gene circuit engineering and
      plasmonic nanomaterials, as well as future research opportunities and challenges
      in photothermal gene manipulation.

PMID- 22954477
TI  - Phase-disorder-induced firing activity in excitable neuronal networks with
      attractive and repulsive coupling.
AB  - It has been revealed that the network of excitable neurons via attractive
      coupling can generate spikes under stimuli of subthreshold signals with
      disordered phases. In this paper, we explore the firing activity induced by phase
      disorder in excitable neuronal networks consisting of both attractive and
      repulsive coupling. By increasing the fraction of repulsive coupling, we find
      that, in the weak coupling strength case, the firing threshold of phase disorder
      is increased and the system response to subthreshold signals is decreased,
      indicating that the effect of inducing neuron firing by phase disorder is
      weakened with repulsive coupling. Interestingly, in the large coupling strength
      case, we see an opposite situation, where the coupled neurons show a rather large
      response to the subthreshold signals even with small phase disorder. The latter
      case implies that the effect of phase disorder is enhanced by repulsive coupling.
      A system of two-coupled excitable neurons is used to explain the role of
      repulsive coupling on phase-disorder-induced firing activity.

PMID- 22954478
TI  - Laplacian twin support vector machine for semi-supervised classification.
AB  - Semi-supervised learning has attracted a great deal of attention in machine
      learning and data mining. In this paper, we have proposed a novel Laplacian Twin
      Support Vector Machine (called Lap-TSVM) for the semi-supervised classification
      problem, which can exploit the geometry information of the marginal distribution
      embedded in unlabeled data to construct a more reasonable classifier and be a
      useful extension of TSVM. Furthermore, by choosing appropriate parameters, Lap
      TSVM degenerates to either TSVM or TBSVM. All experiments on synthetic and real
      data sets show that the Lap-TSVM's classifier combined by two nonparallel
      hyperplanes is superior to Lap-SVM and TSVM in both classification accuracy and
      computation time.

PMID- 22954476
TI  - Hematopoietic stem cells give rise to osteo-chondrogenic cells.
AB  - Repair of bone fracture requires recruitment and proliferation of stem cells with
      the capacity to differentiate to functional osteoblasts. Given the close
      association of bone and bone marrow (BM), it has been suggested that BM may serve
      as a source of these progenitors. To test the ability of hematopoietic stem cells
      (HSCs) to give rise to osteo-chondrogenic cells, we used a single HSC
      transplantation paradigm in uninjured bone and in conjunction with a tibial
      fracture model. Mice were lethally irradiated and transplanted with a clonal
      population of cells derived from a single enhanced green fluorescent protein
      positive (eGFP+) HSC. Analysis of paraffin sections from these animals showed the
      presence of eGFP+ osteocytes and hypertrophic chondrocytes. To determine the
      contribution of HSC-derived cells to fracture repair, non-stabilized tibial
      fracture was created. Paraffin sections were examined at 7 days, 2 weeks and 2
      months after fracture and eGFP+ hypertrophic chondrocytes, osteoblasts and
      osteocytes were identified at the callus site. These cells stained positive for
      Runx-2 or osteocalcin and also stained for eGFP demonstrating their origin from
      the HSC. Together, these findings strongly support the concept that HSCs generate
      bone cells and suggest therapeutic potentials of HSCs in fracture repair.

PMID- 22954479
TI  - A bio-inspired kinematic controller for obstacle avoidance during reaching tasks
      with real robots.
AB  - This paper describes a redundant robot arm that is capable of learning to reach
      for targets in space in a self-organized fashion while avoiding obstacles. Self
      generated movement commands that activate correlated visual, spatial and motor
      information are used to learn forward and inverse kinematic control models while
      moving in obstacle-free space using the Direction-to-Rotation Transform (DIRECT).
      Unlike prior DIRECT models, the learning process in this work was realized using
      an online Fuzzy ARTMAP learning algorithm. The DIRECT-based kinematic controller
      is fault tolerant and can handle a wide range of perturbations such as joint
      locking and the use of tools despite not having experienced them during learning.
      The DIRECT model was extended based on a novel reactive obstacle avoidance
      direction (DIRECT-ROAD) model to enable redundant robots to avoid obstacles in
      environments with simple obstacle configurations. However, certain configurations
      of obstacles in the environment prevented the robot from reaching the target with
      purely reactive obstacle avoidance. To address this complexity, a self-organized
      process of mental rehearsals of movements was modeled, inspired by human and
      animal experiments on reaching, to generate plans for movement execution using
      DIRECT-ROAD in complex environments. These mental rehearsals or plans are self
      generated by using the Fuzzy ARTMAP algorithm to retrieve multiple solutions for
      reaching each target while accounting for all the obstacles in its environment.
      The key aspects of the proposed novel controller were illustrated first using
      simple examples. Experiments were then performed on real robot platforms to
      demonstrate successful obstacle avoidance during reaching tasks in real-world
      environments.

PMID- 22954480
TI  - An incremental neural network with a reduced architecture.
AB  - This paper proposes a technique, called Evolving Probabilistic Neural Network
      (ePNN), that presents many interesting features, including incremental learning,
      evolving architecture, the capacity to learn continually throughout its existence
      and requiring that each training sample be used only once in the training phase
      without reprocessing. A series of experiments was performed on data sets in the
      public domain; the results indicate that ePNN is superior or equal to the other
      incremental neural networks evaluated in this paper. These results also
      demonstrate the advantage of the small ePNN architecture and show that its
      architecture is more stable than the other incremental neural networks evaluated.
      ePNN thus appears to be a promising alternative for a quick learning system and a
      fast classifier with a low computational cost.

PMID- 22954481
TI  - alpha-stability and alpha-synchronization for fractional-order neural networks.
AB  - In this paper, a class of fractional-order neural networks is investigated.
      First, alpha-exponential stability is introduced as a new type of stability and
      some effective criteria are derived for such kind of stability of the addressed
      networks by handling a new fractional-order differential inequality. Based on the
      results, the existence and alpha-exponential stability of the equilibrium point
      are considered. Besides, the synchronization of fractional chaotic networks is
      also proposed. Finally, several examples with numerical simulations are given to
      show the effectiveness of the obtained results.

PMID- 22954482
TI  - Idiopathic pulmonary fibrosis in Taiwan - a population-based study.
AB  - BACKGROUND: This study took advantage of a large population-based database of the
      Taiwan National Health Insurance (NHI) to investigate the epidemiology of
      idiopathic pulmonary fibrosis (IPF) in Taiwan. METHODS: This is a retrospective
      cohort study based on secondary analysis of prospectively collected data in the
      NHI system and governmental data on death registry in Taiwan during 1997-2007. By
      using the broad and narrow definitions for IPF, we estimated incidence and
      prevalence rates of IPF, and its associated clinical outcomes. RESULTS: The
      estimates of annual IPF incidence rates became more stable after 2000, ranging
      between 0.9 and 1.6 cases per 100,000 persons. The prevalence rates became more
      than twofold from 2000 to 2007 (from 2.8 to 6.4 cases per 100,000 persons for the
      broad definition, and from 2.0 to 4.9 cases per 100,000 persons for the narrow
      definition). Men of age older than 75 years had markedly higher incidence and
      prevalence rates than other groups. Around 40% of all incidences and about 30% of
      prevalent cases occurred in this population group. The median survival time after
      IPF diagnosis was 0.9 year (interquartile range (IQR), 0.2-2.5 years) and 0.7
      year (IQR, 0.1-2.3 years) for the broad and narrow definitions, respectively.
      Progression of IPF was the leading cause of death, followed by cancer.
      CONCLUSIONS: In Taiwan, elderly men were the major group suffering from IPF.
      Survival time was short after IPF diagnosis, and the poor survival was largely
      attributable to quick IPF progression after diagnosis.

PMID- 22954483
TI  - Effectiveness of water immersion on postmatch recovery in elite professional
      footballers.
AB  - PURPOSE: The efficacy of a single exposure to 14 min of contrast water therapy
      (CWT) or cold-water immersion (COLD) on recovery postmatch in elite professional
      footballers was investigated. METHOD: Twenty-four elite footballers participated
      in a match followed by 1 of 3 recovery interventions. Recovery was monitored for
      48 h postmatch. Repeat-sprint ability (6 * 20-m), static and countermovement jump
      performance, perceived soreness, and fatigue were measured prematch and
      immediately, 24 h, and 48 h after the match. Soreness and fatigue were also
      measured 1 h postmatch. Postmatch, players were randomly assigned to complete
      passive recovery (PAS; n = 8), COLD (n = 8), or CWT (n = 8). RESULTS: Immediately
      postmatch, all groups exhibited similar psychometric and performance decrements,
      which persisted for 48 h only in the PAS group. Repeat-sprinting performance
      remained slower at 24 and 48 h for PAS (3.9% and 2.0%) and CWT (1.6% and 0.9%)
      but was restored by COLD (0.2% and 0.0%). Soreness after 48 h was most
      effectively attenuated by COLD (ES 0.59 +/- 0.10) but remained elevated for CWT
      (ES 2.39 +/- 0.29) and PAS (ES 4.01 +/- 0.97). Similarly, COLD more successfully
      reduced fatigue after 48 h (ES 1.02 +/- 0.72) than did CWT (ES 1.22 +/- 0.38) and
      PAS (ES 1.91 +/- 0.67). Declines in static and countermovement jump were
      ameliorated best by COLD. CONCLUSIONS: An elite professional football match
      results in prolonged physical and psychometric deficits for 48 h. COLD was more
      successful at restoring physical performance and psychometric measures than CWT,
      with PAS being the poorest.

PMID- 22954484
TI  - Computer skills and internet use in adults aged 50-74 years: influence of hearing
      difficulties.
AB  - BACKGROUND: The use of personal computers (PCs) and the Internet to provide
      health care information and interventions has increased substantially over the
      past decade. Yet the effectiveness of such an approach is highly dependent upon
      whether the target population has both access and the skill set required to use
      this technology. This is particularly relevant in the delivery of hearing health
      care because most people with hearing loss are over 50 years (average age for
      initial hearing aid fitting is 74 years). Although PC skill and Internet use by
      demographic factors have been examined previously, data do not currently exist
      that examine the effects of hearing difficulties on PC skill or Internet use in
      older adults. OBJECTIVE: To explore the effect that hearing difficulty has on PC
      skill and Internet use in an opportunistic sample of adults aged 50-74 years.
      METHODS: Postal questionnaires about hearing difficulty, PC skill, and Internet
      use (n=3629) were distributed to adults aged 50-74 years through three family
      physician practices in Nottingham, United Kingdom. A subsample of 84 respondents
      completed a second detailed questionnaire on confidence in using a keyboard,
      mouse, and track pad. Summed scores were termed the "PC confidence index." The PC
      confidence index was used to verify the PC skill categories in the postal
      questionnaire (ie, never used a computer, beginner, and competent). RESULTS: The
      postal questionnaire response rate was 36.78% (1298/3529) and 95.15% (1235/1298)
      of these contained complete information. There was a significant between-category
      difference for PC skill by PC confidence index (P<.001), thus verifying the three
      category PC skill scale. PC and Internet use was greater in the younger
      respondents (50-62 years) than in the older respondents (63-74 years). The
      younger group's PC and Internet use was 81.0% and 60.9%, respectively; the older
      group's PC and Internet use was 54.0% and 29.8%, respectively. Those with slight
      hearing difficulties in the older group had significantly greater odds of PC use
      compared to those with no hearing difficulties (odds ratio [OR]=1.57, 95%
      confidence interval [CI] 1.06-2.30, P=.02). Those with moderate+ hearing
      difficulties had lower odds of PC use compared with those with no hearing
      difficulties, both overall (OR=0.58, 95% CI 0.39-0.87, P=.008) and in the younger
      group (OR=0.49, 95% CI 0.26-0.86, P=.008). Similar results were demonstrated for
      Internet use by age group (older: OR=1.57, 95% CI 0.99-2.47, P=.05; younger:
      OR=0.32, 95% CI 0.16-0.62, P=.001). CONCLUSIONS: Hearing health care is of
      particular relevance to older adults because of the prevalence of age-related
      hearing loss. Our data show that older adults experiencing slight hearing
      difficulty have increased odds of greater PC skill and Internet use than those
      reporting no difficulty. These findings suggest that PC and Internet delivery of
      hearing screening, information, and intervention is feasible for people between
      50-74 years who have hearing loss, but who would not typically present to an
      audiologist.

PMID- 22954485
TI  - Thromboembolic events and anti-tumor necrosis factor therapies.
AB  - Thromboembolic (TE) events have been observed in about 4.5% of patients treated
      with TNF antagonists. It has been suggested that anti-drug antibodies could be
      involved. However, another mechanism fits more with the available immunochemical
      data and could lead to practical measures to prevent TE events during anti-TNF
      therapies. Adverse effects are not related to the type of antagonist, but well to
      the combination of the inhibition of TNF and the predisposition of some patients
      to lupus-like reactions, including antiphospholipid syndrome. The overproduction
      of interferon-alpha, caused by the inhibition of TNF in these individuals would
      foster the development of lupus-like syndrome. Therefore, seeking conventional
      markers of systemic lupus erythematosus (e.g. anti-dsDNA, anti-phospholipid, anti
      beta(2)-glycoprotein antibodies) before the administration of an anti-TNF could
      be a prudent measure.

PMID- 22954486
TI  - Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like
      synoviocyte migration and invasion through suppression of NF-kappaB-mediated
      matrix metalloproteinase-9 expression.
AB  - Interleukin-17A (IL-17A)-induced migration and invasion of fibroblast-like
      synoviocytes (FLSs) is critical for the pathogenesis of rheumatoid arthritis
      (RA). More than 30% of RA patients are resistant to available therapies, despite
      the introduction of novel biologic agents. Therefore, it is necessary to develop
      new anti-arthritic agents. Recent studies have demonstrated that celastrol has
      anti-arthritic activity in an adjuvant-induced arthritis (AIA) model. However,
      the effect and molecular mechanisms of celastrol on the migration and invasion of
      RA-FLSs are not yet understood. Results showed that treatment of RA-FLSs with
      celastrol suppressed the IL-17A-induced migration and invasion abilities of the
      cells. In addition, celastrol inhibited IL-17A-induced matrix metalloproteinase
      (MMP)-9 mRNA and protein expression, and the proteolytic activity of MMP-9 in RA
      FLSs. Furthermore, our results revealed that celastrol inhibited the
      transcriptional activity of MMP-9 by suppression of the binding activity of
      nuclear factor-kappaB (NF-kappaB) in the MMP-9 promoter, and inhibited
      IkappaBalpha phosphorylation and nuclear translocation of NF-kappaB. In
      conclusion, celastrol can inhibit IL-17A-induced migration and invasion by
      suppressing NF-kappaB-mediated MMP-9 expression in RA-FLSs. These results provide
      a strong rationale for further testing and validation of celastrol as an adjunct
      with conventional drugs for the treatment of RA in humans.

PMID- 22954487
TI  - Engineering new bone via a minimally invasive route using human bone marrow
      derived stromal cell aggregates, microceramic particles, and human platelet-rich
      plasma gel.
AB  - There is a rise in the popularity of arthroscopic procedures in orthopedics.
      However, the majority of cell-based bone tissue-engineered constructs (TECs) rely
      on solid preformed scaffolding materials, which require large incisions and
      extensive dissections for placement at the defect site. Thus, they are not
      suitable for minimally invasive techniques. The aim of this study was to develop
      a clinically relevant, easily moldable, bone TEC, amenable to minimally invasive
      techniques, using human mesenchymal stromal cells (hMSCs) and calcium phosphate
      microparticles in combination with an in situ forming platelet-rich plasma gel
      obtained from human platelets. Most conventional TECs rely on seeding and
      culturing single-cell suspensions of hMSCs on scaffolds. However, for generating
      TECs amenable to the minimally invasive approach, it was essential to aggregate
      the hMSCs in vitro before seeding them on the scaffolds as unaggregated MSCs did
      not generate any bone. Twenty four hours of in vitro aggregation was determined
      to be optimal for maintaining cell viability in vitro and bone formation in vivo.
      Moreover, no statistically significant difference was observed in the amount of
      bone formed when the TECs were implanted via an open approach or a minimally
      invasive route. TECs generated using MSCs from three different human donors
      generated new bone through the minimally invasive route in a reproducible manner,
      suggesting that these TECs could be a viable alternative to preformed scaffolds
      employed through an open surgery for treating bone defects.

PMID- 22954488
TI  - A soy-based product fermented by Enterococcus faecium and Lactobacillus
      helveticus inhibits the development of murine breast adenocarcinoma.
AB  - PURPOSE: Soy and its fermented products are considered functional foods. The
      study objective was to assess three functional food - a non-fermented soy product
      (NFP), fermented soy product (FSP), fermented soy product enriched with
      isoflavones (FI) - in terms of their ability to reduce the development of
      adenocarcinoma in mice, as well their ability on modulating immune system.
      METHODS: It was observed tumor volume and to verify correlations with the immune
      system it was measured levels of the cytokines IL-1beta and TNF-alpha produced by
      macrophages as well as IFN-gamma produced by lymphocytes using ELISA test, and
      nitric oxide production by macrophages using Griess reagent. RESULTS: All
      products showed immunological activity, but FSP showed the most effective tumor
      containment, resulting in smallest tumor volumes. FI animals expressed larger
      amounts of nitric oxide and IL-1beta and exhibited larger tumor sizes than FSP
      and NFP animals. CONCLUSIONS: The results suggested that the ingestion of FSP was
      most efficient in tumor containment, possibly due to a positive modulation of the
      immune system by when Enterococcus faecium and Lactobacillus helveticus are added
      to the soy product.

PMID- 22954489
TI  - Donor-derived bone marrow transfusion produces mixed chimerism and promotes a Th2
      shift in Th1/Th2 balance in rat heterotopic small bowel transplantation.
AB  - BACKGROUND AND AIM: In this study, we investigated immunomodulatory effects of
      donor-derived bone marrow transfusion in rat heterotopic small bowel
      transplantation. METHODS: Rat heterotopic segmental small bowel transplantation
      models (male Brown Norway to female Lewis) were established. The recipients were
      randomly divided into control group (pute small bowel transplantation),
      tacrolimus group (small bowel transplantation plus oral tacrolimus) and small
      bowel transplantation plus oral tacrolimus and intraportal infusion of donor
      derived bone marrow cells group. We investigated the survival time, graft
      pathologic injuries and rejection grade by haematoxylin-eosin staining, serum IL
      2 and IL-10 detection by enzyme labelled immunosorbent assay after small bowel
      transplantation. The recipients mixed chimerism were observed by detecting sex
      determining region of Y chromosome gene in blood, liver, spleen and intestine by
      using real-time polymerase chain reaction and fluorescence in situ hybridization.
      RESULTS: Bone marrow cells group showed a superior survival than the other
      groups, accompanied by milder pathologic injuries and lower rejection grade,
      decreasing serum IL-2 and increasing serum IL-10. The recipient chimerism rate in
      blood, liver, spleen and intestine in bone marrow cells group was significantly
      higher than the other groups. CONCLUSION: Transfusion of donor-derived bone
      marrow cells via portal vein induces mixed chimerism in rats after small bowel
      transplantation, which may promote a Th2 shift in Th1/Th2 balance and facilitate
      the induction of immune tolerance.

PMID- 22954490
TI  - Factors that influence mammography screening behaviour: a qualitative study of
      Greek women's experiences.
AB  - AIM: To identify the factors that influence mammography screening behaviour in a
      sample of Greek women. METHODS/SAMPLE: Data were collected in Athens-Greece, from
      individuals who were members of six women's associations. A subset of 33 women
      were interviewed about their screening behaviour and experiences out of the 186
      women who completed an initial questionnaire. This paper focuses on the findings
      revealed from the interviews. Women's associations were approached for the
      recruitment of the interviewees. RESULTS: Influences arising from women's
      immediate networks, such as family and close friends, appeared to be of essential
      importance in relation to their screening behaviour, while influences from their
      broader networks were of moderate impact. Fear acted as a motivator but also as a
      barrier in relation to mammography screening participation. Experiences that
      arose from engagement with the mammography screening processes were mostly
      characterized by having to overcome a variety of obstacles, such as long
      bureaucratic procedures and distrust in doctors. CONCLUSIONS: The interpersonal
      relationships between women and their social networks appeared to have an
      important and influential role in relation to breast screening behaviour. The
      quality of these relationships appeared to determine women's participation in
      mammography screening. It would appear that future practice needs to focus on
      these relationships in order to utilize them in a positive way. Future research
      is needed to explore this further.

PMID- 22954491
TI  - Further validation of the Patient-Practitioner Orientation Scale (PPOS) from
      recorded visits for back pain.
AB  - OBJECTIVE: More patient-centered communication is associated with improved
      patient satisfaction and health status, fewer malpractice complaints, and
      increased adherence. In a study of medical encounters for acute low back pain
      (LBP), we conducted a secondary analysis to assess the validity of the Patient
      Practitioner Orientation Scale (PPOS), a measure of patient-centeredness.
      METHODS: Fourteen clinicians and 89 of their patients with acute LBP completed
      the PPOS and agreed to have verbal exchanges recorded and coded using the Roter
      Interaction Analysis System (RIAS). We examined correlations between the PPOS and
      counts of patient and provider utterances within 8 RIAS verbal exchange
      categories. RESULTS: Providers with a more patient-centered orientation asked
      fewer biomedical questions, posed more lifestyle questions, gave more lifestyle
      advice, and did more rapport-building. Their patients shared more lifestyle
      information and made more attempts at rapport building and provider engagement.
      In contrast, the patient-centered orientation of patients showed no effect on
      communication. CONCLUSION: The PPOS scores of providers, but not patients,
      predicted significant and meaningful differences in the verbal exchanges of
      patients and providers. PRACTICE IMPLICATIONS: The results support the validity
      of the PPOS measure and provide further evidence of the extent to which provider
      orientation influences patient communication and exchange.

PMID- 22954492
TI  - Pitfalls of HIV genotypic tropism testing after treatment interruption.
AB  - OBJECTIVES: The genotypic method is reliable enough for the determination of
      tropism and largely preferred in Europe. However, careful interpretation is
      essential when assessing HIV genotypic resistance during treatment interruption
      (TI) due to the possible disappearance of resistant strains. The results of HIV
      genotypic tropism testing in such a context remain unknown. METHODS: First, we
      studied changes in tropism in patients included in a structured TI assay: the
      Reverse study. Second, we investigated the unexpected tropism switches from X4 to
      R5 recorded in our routine database. RESULTS: Tropism determination was possible
      in 21 patients of the Reverse study, 9 of whom had an X4 virus (43%) at baseline.
      Two patients displayed a change of tropism during TI, both switching from X4 to
      R5. Regarding the database investigation, 7 of the 222 patients with at least two
      plasma tropism determinations recorded in the database displayed a switch from X4
      to R5. TI due to non-compliance at the time of the tropism change was reported
      for five of these seven patients. CONCLUSIONS: We have shown that the
      redistribution of the HIV population caused by TI could potentially result in X4
      viruses becoming undetected and inappropriate prescription of a CCR5 receptor
      antagonist. Therefore, genotypic tropism results should be interpreted with
      caution in such a context.

PMID- 22954493
TI  - Etravirine concentrations in seminal plasma in HIV-infected patients.
AB  - OBJECTIVES: To determine etravirine concentrations and the HIV-1 viral load (VL)
      in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients. METHODS:
      Ten adult antiretroviral-experienced HIV-1 patients receiving an etravirine
      containing regimen for at least 1 month were enrolled. Semen and blood samples
      were collected ~12 or 24 h after the last etravirine dose, depending on twice
      daily or once-daily dosing, respectively. Liquid chromatography tandem mass
      spectrometry was used to determine etravirine concentrations and HIV-1 VL was
      determined by real-time PCR (detection limit 40 copies/mL). Results are presented
      as the median (range) unless otherwise indicated. RESULTS: Ten blood and 20 semen
      samples were collected. The CD4 count was 502 (252-817) cells/mm(3) and the BP VL
      was <40 (<40-362) copies/mL. The time on etravirine was 52 (12-124) weeks. The BP
      etravirine concentration was 452.5 (258-751) ng/mL. The SP etravirine
      concentration was 62.9 (31.2-166.0) ng/mL and values were above the IC(50) range
      (0.39-2.4 ng/mL) in all cases. The median etravirine SP:BP ratio was 0.16 (0.07
      0.26). The SP VL was <40 copies/mL in all patients, whereas the BP VL was
      detectable in one patient with poor adherence to treatment. CONCLUSIONS:
      Etravirine concentrations in male genital secretions are modest, reaching only
      16% of the BP concentration. Nevertheless, they are more than 10 times greater
      than the wild-type IC(50) range (not adjusted for protein binding).

PMID- 22954495
TI  - Genomic and genome-wide association of susceptibility to radiation-induced
      fibrotic lung disease in mice.
AB  - BACKGROUND AND PURPOSE: To identify genes which influence the fibrotic response
      to thoracic cavity radiotherapy, we combined a genome wide single nucleotide
      polymorphism (SNP) association evaluation of inbred strain response with prior
      linkage and gene expression data. MATERIAL AND METHODS: Mice were exposed to 18Gy
      whole thorax irradiation and survival, bronchoalveolar cell differential, and
      histological alveolitis and fibrosis phenotypes were determined. Association
      analyses were completed with 1.8 million SNPs in single markers and haplotypes.
      RESULTS: Nine strains developed significant fibrosis and 11 strains succumbed to
      alveolitis only or alveolitis with minimal fibrosis. Post irradiation survival
      time (p<0.001) and bronchoalveolar lavage neutrophil percent (p=0.055) were
      correlated with extent of alveolitis and were not significantly correlated with
      fibrosis. Genome wide SNP analysis identified 10 loci as significantly associated
      with radiation-induced fibrotic lung disease (p<8.41*10(-6); by permutation
      test), with the most significant SNP within a conserved non-coding region
      downstream of cell adhesion molecule 1 (Cadm1). Haplotype and SNP analyses
      performed within previously-identified loci revealed additional genes containing
      SNPs associated with fibrosis including Slamf6 and Cdkn1a. CONCLUSION: Combining
      genomic approaches identified variation within specific genes which function in
      the tissue response to injury as associated with fibrosis following thoracic
      irradiation in mice.

PMID- 22954494
TI  - Survival analysis for apparent diffusion coefficient measures in children with
      embryonal brain tumours.
AB  - Embryonal brain tumors constitute a large and important subgroup of pediatric
      brain tumors. Apparent diffusion coefficient (ADC) measures have been previously
      used in the analysis of these tumors. We investigated a newly described ADC
      derived parameter, the apparent transient coefficient in tumor (ATCT), a measure
      of the gradient change of ADC from the peri-tumoral edema into the tumor core, to
      study whether ATCT correlates with survival outcome. Sixty-one patients with
      histologically proven embryonal brain tumors and who had diffusion-weighted
      imaging (DWI) as part of their clinical imaging were enrolled in a retrospective
      study correlating ADC measures with survival. Kaplan-Meier survival curves were
      constructed for extent of surgical resection, age <3 years at diagnosis, tumor
      type, and metastasis at presentation. A multivariate survival analysis was
      performed that took into consideration ATCT and variables found to be significant
      in the Kaplan-Meier analysis as covariates. Results from the multivariate
      analysis showed that ATCT was the only significant covariate (P < .001). Survival
      analysis using Kaplan-Meier curves, dividing the patients into 4 groups of
      increasing values of ATCT, showed that more negative values of ATCT were
      significantly associated with a poorer prognosis (P < .001). A statistically
      significant difference was observed for survival data with respect to the change
      in ADC from edema into the tumor volume. Results show that more negative ATCT
      values are significantly associated with a poorer survival among children with
      embryonal brain tumors, irrespective of tumor type, extent of resection, age <3
      years at diagnosis, and metastasis at presentation.

PMID- 22954496
TI  - Anti-diabetic effects of Centratherum anthelminticum seeds methanolic fraction on
      pancreatic cells, beta-TC6 and its alleviating role in type 2 diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Centratherum anthelminticum (Asteraceae)
      have been popularly used in Ayurvedic medicine to treat diabetes and skin
      disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide
      spread usage in diabetes. AIM OF THE STUDY: To investigate the hypoglycemic
      properties and mechanism of the methanolic fraction of C. anthelminticum seeds
      (CAMFs) on mouse beta-TC6 pancreatic cell line and streptozotocin (STZ)-induced
      diabetic rat models. MATERIALS AND METHODS: We investigated the crude methanolic
      fraction of C. anthelminticum seeds (CAMFs) on beta-TC6 cell line and confirmed
      its effects on type 1 and type 2 diabetic rats to understand its mechanism in
      managing diabetes mellitus. CAMFs were initially tested on beta-TC6 cells for
      cytotoxicity, 2-NBDG glucose uptake, insulin secretion and glucose transporter
      (GLUT-1, 2 and 4) protein expression. Furthermore, streptozotocin (STZ)-induced
      type 1 diabetic and STZ-nicotinamide-induced type 2 diabetic rats were
      intraperitoneally (i.p) injected or administered orally with CAMFs daily for 28
      days. The effect of CAMFs on blood glucose and insulin levels was subsequently
      evaluated. RESULTS: In cell line studies, CAMFs showed non-cytotoxic effect on
      beta-TC6 cell proliferation compared to untreated control cells at 50 MUg/ml.
      CAMFs increased glucose uptake and insulin secretion dose-dependently by up
      regulating GLUT-2 and GLUT-4 expression in these cells. Further in vivo studies
      on streptozotocin induced diabetic rat models revealed that CAMFs significantly
      reduced hyperglycemia by augmenting insulin secretion in type 2 diabetic rats.
      However, CAMFs displayed less significant effects on type 1 diabetic rats.
      CONCLUSIONS: CAMFs demonstrated anti-diabetic potential on beta-TC6 cells and
      type 2 diabetic rat model, plausibly through enhancing glucose uptake and insulin
      secretion.

PMID- 22954497
TI  - alpha-Glucosidase inhibitory activity of selected Philippine plants.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Antidesma bunius Spreng. (Phyllantaceae),
      Averrhoa bilimbi L. (Oxalidaceae), Biophytum sensitivum (L.) DC. (Oxalidaceae),
      Ceriops tagal (Perr.) C.B. Rob. (Rhizophoraceae), Kyllinga monocephala Rottb.
      (Cyperaceae), and Rhizophora mucronata Lam. (Rhizophoraceae) are used as remedies
      to control diabetes. In the present study, these plants were screened for their
      potential alpha-glucosidase inhibitory activity. MATERIALS AND METHODS: The 80%
      aqueous ethanolic extracts were screened for their alpha-glucosidase enzyme
      inhibitory activity using yeast alpha glucosidase enzyme. RESULTS: Except for A.
      bilimbi with IC(50) at 519.86+/-3.07, all manifested a significant enzyme
      inhibitory activity. R. mucronata manifested the highest activity with IC(50) at
      0.08+/-1.82 MUg mL(-1), followed by C. tagal with IC(50) at 0.85+/-1.46 MUg mL(
      1) and B. sensitivum with IC(50) at 2.24+/-1.58 MUg mL(-1). CONCLUSION: This is
      the first report on the alpha-glucosidase inhibitory effect of the six Philippine
      plants; thus, partly defining the mechanism on why these medicinal plants possess
      antidiabetic properties.

PMID- 22954499
TI  - 'Supersize me': on equine obesity.

PMID- 22954498
TI  - Evaluation of hepatotoxicity and cholestasis in rats treated with EtOH extract of
      Fructus Psoraleae.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP) has been widely used to
      heal skin diseases as well as osteoporosis, osteomalacia, and bone fracture.
      There also exist many clinical reports about FP-induced hepatotoxicity associated
      with acute cholestatic hepatic injury. However, the FP-induced hepatotoxicity and
      the underlying mechanisms remain unclear. AIMS OF THE STUDY: The present study
      aims to determine the hepatotoxicity of FP in Sprague-Dawley (SD) rats and to
      investigate the underlying mechanisms. MATERIALS AND METHODS: Sprague-Dawley rats
      of both sexes were intragastrically administered with the EtOH extract of FP
      (EEFP) at doses of 1.875, 1.25 and 0.625 g/kg for 28 day. Body weight, relative
      liver weight, biochemical analysis, histopathology, the mRNA and protein
      expression of Cholesterol 7alpha-hydroxylase (CYP7A1), farnesoid X receptor
      (FXR), bile-salt export pump (BSEP), multidrug resistance-associated protein 2
      (MRP2), multidrug resistance-associated protein 3 (MRP3) were evaluated to study
      the EEFP-induced hepatotoxicity and its underlying mechanisms. RESULTS: Many
      abnormalities were observed in the EEFP-treated groups including suppression of
      weight gain and food intake, change of some parameters in serum biochemistry,
      increased weight of liver, and decreased concentration of bile acid in bile. The
      mRNA and protein expression of CYP7A1, MRP3, MRP2, BSEP increased and the
      expression of FXR decreased in EEFP-treated female groups; the mRNA and protein
      of FXR and CYP7A1 decreased and that of the others remained the same in EEFP
      treated male groups. CONCLUSION: In conclusion, we provide evidence for the first
      time that EEFP can induce sex-related cholestatic hepatotoxicity, and that female
      rats are more sensitive to EEFP-induced hepatotoxicity, which involves the
      destruction of the biosynthesis and transportation of bile acid. Further
      investigation is still needed to uncover the mechanism of the sex-dimorphic EEFP
      induced hepatotoxicity.

PMID- 22954500
TI  - Measuring the acoustoelectric interaction constant using ultrasound current
      source density imaging.
AB  - Ultrasound current source density imaging (UCSDI) exploits the acoustoelectric
      (AE) effect, an interaction between ultrasound pressure and electrical
      resistivity, to map electrical conduction in the heart. The conversion efficiency
      for UCSDI is determined by the AE interaction constant K, a fundamental property
      of all materials; K directly affects the magnitude of the detected voltage signal
      in UCSDI. This paper describes a technique for measuring K in biological tissue,
      and reports its value for the first time in cadaver hearts. A custom chamber was
      designed and fabricated to control the geometry for estimating K, which was
      measured in different ionic salt solutions and seven cadaver rabbit hearts. We
      found K to be strongly dependent on concentration for the divalent salt CuSO(4),
      but not for the monovalent salt NaCl, consistent with their different chemical
      properties. In the rabbit heart, K was determined to be 0.041 +/- 0.012%/MPa,
      similar to the measurement of K in physiological saline (0.034 +/- 0.003%/MPa).
      This study provides a baseline estimate of K for modeling and experimental
      studies that involve UCSDI to map cardiac conduction and reentry currents
      associated with arrhythmias.

PMID- 22954501
TI  - Sexual pleasure and sexual risk among women who use methamphetamine: a mixed
      methods study.
AB  - BACKGROUND: The intersection of drug use, sexual pleasure and sexual risk
      behaviour is rarely explored when it comes to poor women who use drugs. This
      paper explores the relationship between sexual behaviour and methamphetamine use
      in a community-based sample of women, exploring not only risk, but also desire,
      pleasure and the challenges of overcoming trauma. METHODS: Quantitative data were
      collected using standard epidemiological methods (N=322) for community-based
      studies. In addition, using purposive sampling, qualitative data were collected
      among a subset of participants (n=34). Data were integrated for mixed methods
      analysis. RESULTS: While many participants reported sexual risk behaviour
      (unprotected vaginal or anal intercourse) in the quantitative survey, sexual risk
      was not the central narrative pertaining to sexual behaviour and methamphetamine
      use in qualitative findings. Rather, desire, pleasure and disinhibition arose as
      central themes. Women described feelings of power and agency related to sexual
      behaviour while high on methamphetamine. Findings were mixed on whether
      methamphetamine use increased sexual risk behaviour. CONCLUSION: The use of mixed
      methods afforded important insights into the sexual behaviour and priorities of
      methamphetamine-using women. Efforts to reduce sexual risk should recognize and
      valorize the positive aspects of methamphetamine use for some women, building on
      positive feelings of power and agency as an approach to harm minimization.

PMID- 22954502
TI  - Online advertising to reach and recruit Latino smokers to an internet cessation
      program: impact and costs.
AB  - BACKGROUND: Tobacco cessation among Latinos is a public health priority in the
      United States, particularly given the relatively high growth of this population
      segment. Although a substantial percentage of American Latinos use the Internet,
      they have not engaged in Web-based cessation programs as readily as other
      racial/ethnic subgroups. A lack of culturally specific advertising efforts may
      partly explain this disparity. OBJECTIVE: Phase I of this study focused on the
      development of four Spanish-language online banner advertisements to promote a
      free Spanish-language smoking cessation website (es.BecomeAnEX.org). Phase II
      examined the relative effectiveness of the four banner ads in reaching and
      recruiting Latino smokers to the cessation website. METHODS: In Phase I, 200
      Spanish-speaking Latino smokers completed an online survey to indicate their
      preference for Spanish-language banner ads that incorporated either the cultural
      value of family (familismo) or fatalism (fatalismo). Ads included variations on
      message framing (gain vs loss) and depth of cultural targeting (surface vs deep).
      In Phase II, a Latin square design evaluated the effectiveness of the four
      preferred ads from Phase I. Ads were systematically rotated across four popular
      Latino websites (MySpace Latino, MSN Latino, MiGente, and Yahoo! en Espanol) over
      four months from August to November 2009. Tracking software recorded ad clicks
      and registrants on the cessation website. Negative binomial regression and
      general linear modeling examined the main and interacting effects of message
      framing and depth of cultural targeting for four outcomes: number of clicks,
      click-through rate, number of registrants, and cost per registrant. RESULTS: In
      Phase I, smokers preferred the four ads featuring familismo. In Phase II,
      24,829,007 impressions were placed, yielding 24,822 clicks, an overall click
      through rate of 0.10%, and 500 registrants (2.77% conversion rate). Advertising
      costs totaled US $104,669.49, resulting in an overall cost per click of US $4.22
      and cost per registrant of US $209.34. Website placement predicted all four
      outcomes (all P values < .01). Yahoo! en Espanol yielded the highest click
      through rate (0.167%) and number of registrants (n = 267). The message framing
      and cultural targeting interaction was not significant. Contrary to hypotheses,
      loss-framed ads yielded a higher click-through rate than gain-framed ads (point
      estimate = 1.08, 95% CI 1.03 1.14, P = 0.004), and surface-targeted ads
      outperformed deep-targeted ads for clicks (point estimate = 1.20, 95% CI 1.13
      1.28, P < .001), click-through rate (point estimate = 1.22, 95% CI 1.16 1.29, P <
      .001), and number of registrants (point estimate = 2.73, 95% CI 2.14 3.48, P <
      .001). CONCLUSIONS: Online advertising can be an effective and cost-efficient
      strategy to reach and engage Spanish-speaking Latino smokers in an evidence-based
      Internet cessation program. Cultural targeting and smoking-relevant images may be
      important factors for banner ad design. Online advertising holds potential for
      Web-based cessation program implementation and research.

PMID- 22954504
TI  - Efficacy and safety of capecitabine in heavily pretreated recurrent/metastatic
      head and neck squamous cell carcinoma.
AB  - The objective of this study was to evaluate the efficacy and tolerability of
      capecitabine as a single agent in the treatment of recurrent/metastatic head and
      neck squamous cell carcinoma. Patients were treated with oral capecitabine
      according to good clinical practice. Efficacy and safety outcomes were analyzed
      retrospectively. The response and adverse events rates and their exact confidence
      intervals (CIs) were calculated. Survival distributions were estimated using the
      Kaplan-Meier method. Twenty-nine patients were included in the study. Twenty-five
      patients (86%) had received at least three previous lines of chemotherapy. The
      disease control rate was 48% (95% CI: 29-67%). The median progression-free
      survival was 2.0 months (95% CI: 0.1-3.9 months) and the median overall survival
      was 7.0 months (95% CI: 4.1-9.9 months). Hand-foot syndrome, fatigue, and
      mucositis were the most frequent severe side effects. No patient died, and only
      three patients discontinued treatment because of side effects. Capecitabine seems
      to be an active and well-tolerated regimen, even in heavily pretreated, frail
      patients. LEVEL OF EVIDENCE: 2C 'Outcomes Research'.

PMID- 22954505
TI  - Is adjuvant chemotherapy useful for soft-tissue sarcomas?

PMID- 22954503
TI  - Chemoreceptors, baroreceptors, and autonomic deregulation in children with
      obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is highly prevalent sleep disorder of breathing in
      both adults and children that is fraught with substantial cardiovascular
      morbidities, the latter being attributable to a complex interplay between
      intermittent hypoxia (IH), episodic hypercapnia, recurrent large intra-thoracic
      pressure swings, and sleep disruption. Alterations in autonomic nervous system
      function could underlie the perturbations in cardiovascular, neurocognitive,
      immune, endocrine and metabolic functions that affect many of the patients
      suffering from OSA. Although these issues have received substantial attention in
      adults, the same has thus far failed to occur in children, creating a quasi
      misperception that children are protected. Here, we provide a critical overview
      of the evidence supporting the presence of autonomic nervous system (ANS)
      perturbations in children with OSA, draw some parallel assessments to known
      mechanisms in rodents and adult humans, particularly, peripheral and central
      chemoreceptor and baroreceptor pathways, and suggest future research directions.

PMID- 22954506
TI  - Crizotinib in ALK-positive lung cancer.

PMID- 22954507
TI  - Activity and safety of crizotinib in patients with ALK-positive non-small-cell
      lung cancer: updated results from a phase 1 study.
AB  - BACKGROUND: ALK fusion genes occur in a subset of non-small-cell lung cancers
      (NSCLCs). We assessed the tolerability and activity of crizotinib in patients
      with NSCLC who were prospectively identified to have an ALK fusion within the
      first-in-man phase 1 crizotinib study. METHODS: In this phase 1 study, patients
      with ALK-positive stage III or IV NSCLC received oral crizotinib 250 mg twice
      daily in 28-day cycles. Endpoints included tumour responses, duration of
      response, time to tumour response, progression-free survival (PFS), overall
      survival at 6 and 12 months, and determination of the safety and tolerability and
      characterisation of the plasma pharmacokinetic profile of crizotinib after oral
      administration. Responses were analysed in evaluable patients and PFS and safety
      were analysed in all patients. This study is registered with ClinicalTrials.gov,
      number NCT00585195. FINDINGS: Between Aug 27, 2008, and June 1, 2011, 149 ALK
      positive patients were enrolled, 143 of whom were included in the response
      evaluable population. 87 of 143 patients had an objective response (60.8%, 95% CI
      52.3-68.9), including three complete responses and 84 partial responses. Median
      time to first documented objective response was 7.9 weeks (range 2.1-39.6) and
      median duration of response was 49.1 weeks (95% CI 39.3-75.4). The response rate
      seemed to be largely independent of age, sex, performance status, or line of
      treatment. Median PFS was 9.7 months (95% CI 7.7-12.8). Median overall survival
      data are not yet mature, but estimated overall survival at 6 and 12 months was
      87.9% (95% CI 81.3-92.3) and 74.8% (66.4-81.5), respectively. 39 patients
      continued to receive crizotinib for more than 2 weeks after progression because
      of perceived ongoing clinical benefit from the drug (12 for at least 6 months
      from the time of their initial investigator-defined disease progression).
      Overall, 144 (97%) of 149 patients experienced treatment-related adverse events,
      which were mostly grade 1 or 2. The most common adverse events were visual
      effects, nausea, diarrhoea, constipation, vomiting, and peripheral oedema. The
      most common treatment-related grade 3 or 4 adverse events were neutropenia (n=9),
      raised alanine aminotransferase (n=6), hypophosphataemia (n=6), and lymphopenia
      (n=6). INTERPRETATION: Crizotinib is well tolerated with rapid, durable responses
      in patients with ALK-positive NSCLC. There seems to be potential for ongoing
      benefit after initial disease progression in this population, but a more formal
      definition of ongoing benefit in this context is needed.

PMID- 22954508
TI  - Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected
      soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial.
AB  - BACKGROUND: The effect of adjuvant chemotherapy on survival for resected soft
      tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant
      chemotherapy on survival in patients after resection of high-risk soft-tissue
      sarcomas. METHODS: In this multicentre randomised trial, patients with
      macroscopically resected, Trojani grade II-III soft-tissue sarcomas at any site,
      no metastases, performance status lower than 2 and aged between 16 and 70 years
      were eligible within 4 weeks of definitive surgery. Patients were randomly
      assigned to receive adjuvant chemotherapy or no chemotherapy (control group).
      Randomisation was done with a minimisation technique, stratified by hospital,
      site of primary tumour, tumour size, planned radiotherapy, and isolated limb
      perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75
      mg/m(2), ifosfamide 5 g/m(2), and lenograstim every 3 weeks. Patients in both
      groups received radiotherapy if the resection was marginal or the tumour
      recurrent. The primary endpoint was overall survival and analyses were done by
      intention to treat. The final results are presented. This trial is registered
      with ClinicalTrials.gov, NCT00002641. FINDINGS: Between February, 1995, and
      December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy
      group (175 patients) or to the control group (176). 258 (73%) of 351 patients
      received radiotherapy, 129 in each group. Overall survival did not differ
      significantly between groups (hazard ratio [HR] 0.94 [95% CI 0.68-1.31], p=0.72)
      nor did relapse-free survival (HR 0.91 [0.67-1.22], p=0.51). 5-year overall
      survival rate was 66.5% (58.8-73.0) in the chemotherapy group and 67.8% (60.3
      74.2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of
      163 patients who started it completing all five cycles. 16 (10%) patients had
      grade 3 or 4 fever or infection, but no deaths due to toxic effects were
      recorded. INTERPRETATION: Adjuvant chemotherapy with doxorubicin and ifosfamide
      in resected soft-tissue sarcoma showed no benefit in relapse-free survival or
      overall survival. Future studies should focus on patients with larger, grade III,
      and extremity sarcomas.

PMID- 22954509
TI  - A novel approach for lactate threshold assessment based on rating of perceived
      exertion.
AB  - This study tested the hypothesis that the DMAX (for maximal distance) method
      could be applied to ratings of perceived exertion (RPE), to propose a novel
      method for individual detection of the lactate threshold (LT) using RPE alone
      during an incremental test to exhaustion. Twenty-one participants performed an
      incremental test on a cycle ergometer. At the end of each stage, lactate
      concentration was measured and the participants estimated RPE using the Borg
      CR100 scale. The intensity corresponding to the fixed lactate values of 2 or 4
      mmol . L-1 (2mM and 4mM), the ventilatory threshold (VT), the respiratory
      compensation point (RCP), and the instant of equality of pulmonary gas exchange
      (RER=1.00) were determined. Lactate (DMAX La) and RPE (DMAX RPE) thresholds were
      determined using the DMAX method. Oxygen uptake (VO2), heart rate, and power
      output measured at DMAX RPE and at DMAX La were not statistically different.
      Bland-Altman plots showed small bias and good agreements when DMAX RPE was
      compared with the DMAX La and RER=1.00 methods (bias = -0.05% and -2% of VO2max,
      respectively). Conversely, VO2 from the DMAX RPE method was lower than VO2 at 4
      mM and at RCP and was higher than VO2 at 2 mM and at VT. VO2 at DMAX RPE was
      strongly correlated with VO2 at DMAX La (r = .97), at RER=1.00 (r = .97), at 2 mM
      (r = .85), at 4 mM (r = .93), at VT (r = .95), and at RCP (r = .95). The
      combination of the DMAX method with the RPE responses permitted precise and
      individualized estimates of LT using the DMAX method.

PMID- 22954511
TI  - Criminal justice and alcohol treatment: results from a national sample.
AB  - This study investigates the associations of recent criminal justice involvement
      with perceived need for alcohol treatment and alcohol treatment utilization,
      adjusting for demographic and clinical characteristics. We examined a national
      sample of adults with alcohol use disorders (N=4390) from the 2006 National
      Survey on Drug Use and Health. Almost 15% reported criminal justice involvement
      in the past year. Generalized logit models regressed perceived need for alcohol
      or drug treatment and past year treatment utilization (versus neither) on past
      year legal involvement, demographic, and clinical information. In general,
      results found stronger associations between frequency of criminal justice
      involvement for treatment utilization compared to perceived need for treatment
      alone. Treatment utilization was also associated with being on probation, arrests
      for drug possession/sale and driving under the influence but perceived need was
      not. Study results suggest opportunities for interventions to increase treatment
      rates or treatment need, a major correlate of treatment utilization.

PMID- 22954510
TI  - Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone
      on subjective responses to alcohol.
AB  - Naltrexone, one of four FDA-approved pharmacotherapies for alcohol dependence,
      has shown moderate efficacy in clinical trials. Pharmacogenetic effects have been
      reported such that allelic variation at the gene encoding the mu-opioid receptor
      (OPRM1, rs1799971) predicts naltrexone-induced blunting of the positively
      reinforcing effects of alcohol. However, naltrexone also binds, albeit to a
      lesser degree, to kappa and delta opioid receptors in the brain. This alternate
      binding presents the possibility that single nucleotide polymorphisms (SNPs) in
      the kappa and delta opioid receptor (OPRK1 and OPRD1) genes may contribute to
      naltrexone pharmacogenetics. Therefore, the goal of this exploratory study was to
      re-examine data from a double-blind placebo controlled laboratory trial of
      naltrexone for pharmacogenetic effects at kappa and delta opioid receptor tag
      SNPs. Participants were 40 heavy drinkers (12 female) who underwent an
      intravenous alcohol challenge paradigm after receiving naltrexone (50mg) or
      placebo in randomized and crossover fashion. Dependent variables were self
      reported alcohol-induced stimulation, sedation, and craving. Multilevel models
      revealed a significant Naltrexone*OPRK1 Genotype (rs997917) interaction
      predicting alcohol-induced sedation, such that TT homozygotes reported lower
      naltrexone-induced alcohol sedation as compared to carriers of the C allele.
      Moreover, there was a significant Naltrexone*OPRD1 Genotype (rs4654327)
      interaction predicting alcohol-induced stimulation and craving, such that
      carriers of the A allele at this locus reported greater naltrexone-induced
      blunting of alcohol stimulation and alcohol craving compared to GG homozygotes.
      These findings suggest that additional pharmacogenetic effects in the opioid
      receptor system may account for individual differences in response to naltrexone
      in the human laboratory.

PMID- 22954513
TI  - Posterior reversible encephalopathy syndrome in children: radiological and
      clinical findings - a retrospective analysis of a German tertiary care center.
AB  - PURPOSE: To report the radiological and clinical spectrum of posterior reversible
      encephalopathy syndrome (PRES) in children in a German tertiary referral center.
      METHODS: The radiological report data bases of the authors' university hospitals
      were searched for paediatric patients with PRES. Clinical and paraclinical data
      as well as various imaging features at symptom onset and during follow-up were
      tabulated in patients fulfilling the criteria for PRES. RESULTS: A total of 18
      paediatric patients with PRES were included into the study. Mean age was 9 years
      (IQR 7-12), 38.9% were females. Most frequent predisposing causes were renal and
      haemato-oncologic diseases frequently associated with endotheliotoxic cytostatic
      medication. Frontal lesions occurred as frequently as parietal lesions followed
      by occipital lesions. The superior frontal sulcus topographic lesion pattern
      occurred as frequent as the parieto-occipital one. In 38% of cases residual
      lesions were encountered with focal laminar necroses being most frequent. Initial
      clinical syndromes associated with PRES included seizures in 18, altered mental
      state in 5, and hemiparesis and visual disturbances in 2 children. Mean arterial
      blood pressure at onset of PRES was 140/85 mmHg (IQR systolic: 124-169,
      diastolic: 78-93 mmHg). CONCLUSION: Paediatric PRES in this cohort comprises a
      broad radiological and clinical spectrum. The occurrence of frontal lesions, a
      superior frontal sulcus associated lesion pattern, and the development of focal
      laminar necrosis appear to be frequent in children.

PMID- 22954514
TI  - Children with autism spectrum disorders - the importance of medical
      investigations.
AB  - BACKGROUND: Considerable knowledge about medical comorbidity in cases of Autism
      Spectrum Disorders (ASD) is available, still it is not well established how
      extensive the medical investigations should be in individual cases. The aim is to
      explore proportions of possible specific medical conditions in ASD. METHODS: 79
      subjects went through extensive medical evaluations according to pre-defined
      procedures, including medical and developmental history, physical and biomedical
      investigations. RESULTS: Clinical neurological findings were quite common, and we
      found a high number of pathological findings in the additional medical
      investigations. Our study revealed that these pathological deviations occurred
      more frequently in patients with childhood autism than in the other diagnostic
      sub-groups, the exception were chromosomal findings which occurred more often in
      patients not-diagnosed with childhood autism. CONCLUSION: Medical and laboratory
      investigations should still be performed as a consequence of the patient's
      history, clinical presentations or family history. We should basically continue
      the use of non-routine and invasive procedures which do not put the patient at
      some unnecessary risk, in the absence of relevant clinical indications.

PMID- 22954515
TI  - Non-amyloidogenic peptide tags for the regulatable self-assembling of protein
      only nanoparticles.
AB  - Controlling the self-assembling of building blocks as nanoscale entities is a
      requisite for the generation of bio-inspired vehicles for nanomedicines. A wide
      spectrum of functional peptides has been incorporated to different types of
      nanoparticles for the delivery of conventional drugs and nucleic acids, enabling
      receptor-specific cell binding and internalization, endosomal escape, cytosolic
      trafficking, nuclear targeting and DNA condensation. However, the development of
      architectonic tags to induce the self-assembling of functionalized monomers has
      been essentially neglected. We have examined here the nanoscale architectonic
      capabilities of arginine-rich cationic peptides, that when displayed on His
      tagged proteins, promote their self-assembling as monodisperse, protein-only
      nanoparticles. The scrutiny of the cross-molecular interactivity cooperatively
      conferred by poly-arginines and poly-histidines has identified regulatable
      electrostatic interactions between building blocks that can also be engineered to
      encapsulate cargo DNA. The combined use of cationic peptides and poly-histidine
      tags offers an unusually versatile approach for the tailored design and
      biofabrication of protein-based nano-therapeutics, beyond the more limited
      spectrum of possibilities so far offered by self-assembling amyloidogenic
      peptides.

PMID- 22954512
TI  - Myosins in cell junctions.
AB  - The development of cell-cell junctions was a fundamental step in metazoan
      evolution, and human health depends on the formation and function of cell
      junctions. Although it has long been known that actin and conventional myosin
      have important roles in cell junctions, research has begun to reveal the specific
      functions of the different forms of conventional myosin. Exciting new data also
      reveals that a growing number of unconventional myosins have important roles in
      cell junctions. Experiments showing that cell junctions act as mechanosensors
      have also provided new impetus to understand the functions of myosins and the
      forces they exert. In this review we will summarize recent developments on the
      roles of myosins in cell junctions. 

PMID- 22954516
TI  - The effect of the degree of sulfation of glycosaminoglycans on osteoclast
      function and signaling pathways.
AB  - To meet the growing need for bone replacement of our aging population,
      development of new adaptive biomaterials is essential. Collagen and
      glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS)
      are major components of the extracellular matrix (ECM) in bone. We manufactured
      native and sulfate-modified GAG matrices, evaluated how these components modulate
      different functions of osteoclasts, the cells that resorb bone, and analyzed the
      underlying mechanisms. GAGs were tested for their effects on osteoclast adhesion,
      viability, differentiation, morphology, and resorption as well as proteome
      alterations using murine RAW264.7 cells and primary human osteoclasts. Native and
      sulfated GAGs were stable and largely non-cytotoxic. Sulfation of GAGs led to a
      significant inhibition of osteoclast differentiation and resorption, which was
      largely dependent on the degree of sulfation of GAGs rather than the
      monosaccharide composition. Sulfation significantly reduced resorptive function
      by 14% (CS) and 43% (HA). Highly sulfated GAGs dose-dependently suppressed
      osteoclast differentiation, osteoclast-specific expression of TRAP, cathepsin K,
      SWAP-70, and OSCAR by 63-95%, and inhibited proteins involved in cytoskeletal
      rearrangement. In conclusion, highly sulfated GAGs significantly inhibit various
      functions of bone-resorbing osteoclasts. Whether these properties locally
      contribute to improved fracture or bone defect healing needs to be validated in
      vivo.

PMID- 22954517
TI  - Super long-term glycemic control in diabetic rats by glucose-sensitive LbL films
      constructed of supramolecular insulin assembly.
AB  - The supramolecular assembly of porcine insulin (P-SIA) is prepared at moderate
      condition and monitored by Thioflavin T fluorescence to avoid the formation of
      mature amyloid fibrils with beta-sheet rich structure. P-SIA is characterized in
      terms of structure, morphology and the capability of sustained insulin release in
      vitro. Then, a glucose-sensitive layer-by-layer (LbL) film is fabricated with
      star poly[2-(dimethylamino)ethyl methacrylate] (star-PDMAEMA), glucose oxidase
      (GOD), catalase (CAT) and P-SIA in the form of {(Star-PDMAEMA/P-SIA)(2) + (Star
      PDMAEMA/CAT)(1) + (Star-PDMAEMA/GOD)(2)}(2) + Star-PDMAEMA, in which the CAT is
      introduced to eliminate the aggregated H(2)O(2) and maintain the activity of GOD
      in the long release time. Within the scope of the investigation, a single dose
      administration could provide effective glycemic control in diabetic rats for up
      to 295 days without hypoglycemia. The striking result is contributed both by the
      inherent property of P-SIA and the glucose-sensitive regulation capability of the
      LbL film, for which the mechanism was thoroughly investigated both in vitro and
      in vivo. These findings are valuable to inspire more researches to combine
      supramolecular insulin assembly with various functional drug delivery systems,
      biochemical additives, biomaterials and biomedical devices for diabetic therapy.

PMID- 22954519
TI  - A computerized compact module for separation of (99m)Tc-radionuclide from
      molybdenum.
AB  - An automated closed cycle module for the separation and recovery of various
      isotopes, radioactive or non-radioactive, using solvent extraction and column
      chromatography techniques, and in particular, for separation and recovery of
      (99m)Tc from low-medium specific activity (99)Mo, is described. The module may
      also be applicable for separation of (99m)Tc produced in a cyclotron. The module
      is safe and reliable to avoid human interference and hazards posed by handling of
      radioactive and hazardous chemicals. The entire system of automation includes a
      user-friendly PC based graphical user interface (GUI) that actually supervises
      the process via an embedded system based electronic controller.

PMID- 22954520
TI  - Power density spectrum for the identification of residence time distribution
      signals.
AB  - One of the most important applications of radioisotopes in industry is the
      residence time distribution (RTD) measurement. RTD can be used for optimizing the
      design of industrial systems and determining their malfunctions. The RTD signal
      may be subject to different sorts of noise. This leads to errors in the RTD
      calculations, and hence leads to wrong analysis in the determination of system
      malfunctions. This paper presents a proposed approach for RTD signal
      identification based on power density spectrum (PDS). The cepstral features are
      extracted from the signal or/and its PDS. The PDS is estimated using
      nonparametric, parametric, and eigen-analysis methods. The identification results
      are analyzed and compared for different estimation methods in order to select the
      best PDS estimation method for RTD signal identification. Neural networks are
      used for training and testing in the proposed approach. The proposed approach is
      tested using RTD signals obtained from the measurements carried out with
      radiotracer technique. The experimental results show that the proposed approach
      with features extracted from the PDS of the RTD signals calculated using eigen
      analysis methods is the most robust and reliable in RTD signal identification.

PMID- 22954518
TI  - Childhood sexual abuse and risk for initiating injection drug use: a prospective
      cohort study.
AB  - OBJECTIVE: This study examined whether childhood sexual abuse predicts initiation
      of injection drug use in a prospective cohort of youth. METHOD: From October 2005
      to November 2010, data were collected from the At Risk Youth Study (ARYS), a
      prospective cohort study of street-involved youth in Vancouver, Canada. Inclusion
      criteria were age 14-26 years, no lifetime drug injection, and non-injection drug
      use in the month preceding enrollment. Participants were interviewed at baseline
      and semiannually thereafter. Cox regression was employed to identify risk factors
      for initiating injection. RESULTS: Among 395 injection-naive youth, 81 (20.5%)
      reported childhood sexual abuse. During a median follow-up of 15.9 months (total
      follow-up 606.6 person-years), 45 (11.4%) youth initiated injection drug use,
      resulting in an incidence density of 7.4 per 100 person-years. In univariate
      analyses, childhood sexual abuse was associated with increased risk of initiating
      injection (unadjusted hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.29
      4.38; p=0.006), an effect that persisted in multivariate analysis despite
      adjustment for gender, age, aboriginal ancestry and recent non-injection drug use
      (adjusted HR, 2.71; 95% CI, 1.42-5.20; p=0.003). CONCLUSION: Childhood sexual
      abuse places drug users at risk for initiating injection. Addiction treatment
      programs should incorporate services for survivors of childhood maltreatment.

PMID- 22954522
TI  - Effects of statins on liver cell function and inflammation in septic rats.
AB  - BACKGROUND: Several studies suggest that the presence of statins may be
      beneficial during sepsis, but this idea is controversial. The aim of this study
      was to investigate the effects of long-term statin treatment in the livers of
      septic animals, focusing on its antioxidant, antiinflammatory, and metabolic
      properties. MATERIALS AND METHODS: Male Wistar rats were treated orally with
      simvastatin, atorvastatin, or vehicle once a d. After 30 d, sepsis was induced by
      cecal ligation and puncture (CLP) in Control, Simvastatin-treated, and
      Atorvastatin-treated groups, while the Sham group underwent only laparotomy. The
      Basal Simvastatin and Basal Atorvastatin groups received only their respective
      drugs without surgery. Twenty-four h after CLP or laparotomy, samples were
      collected from anesthetized rats for evaluation of hepatic oxidative stress,
      liver histology, hepatic mitochondria enzyme activity, leukocyte counts in blood
      and peritoneal cavity, gene expression of hepatic superoxide dismutase and TNF-2,
      and plasma biochemistry. RESULTS: Most parameters that we tested exhibited
      expected changes upon sepsis induction. However, statin treatment only improved
      liver mitochondrial enzymatic activity. In other parameters, simvastatin and
      atorvastatin failed to protect the liver against injuries incurred upon the CLP
      induced polymicrobial sepsis model. CONCLUSIONS: Pretreatment with simvastatin or
      atorvastatin alone before sepsis induction improved mitochondrial activity in the
      liver; however, this result was not reproduced in other biomarkers of liver
      function and leukocyte migration during sepsis. Future studies should be
      performed to evaluate whether statins can be combined with other drugs to
      increase the efficacy of sepsis therapy.

PMID- 22954523
TI  - Pterostilbene ameliorates tumor necrosis factor alpha-induced pancreatitis in
      vitro.
AB  - BACKGROUND: We have previously demonstrated that pterostilbene, a compound in
      blueberries, exerts antiproliferative effects against pancreatic adenocarcinoma.
      However, little is known about the anti-inflammatory effects of pterostilbene in
      pancreatitis. Therefore, the aim of this study was to evaluate the effect of
      pterostilbene on inflammatory markers in an in vitro pancreatitis model. We
      hypothesized that pterostilbene would ameliorate the immediate inflammatory
      response in tumor necrosis factor alpha (TNF-alpha)-induced pancreatitis through
      downregulation of signal transducer and activator of transcription 3 (STAT3) and
      inhibition of TNF-alpha-induced secretion of lipase and proinflammatory cytokines
      interleukins (ILs) 1beta and 6. METHODS: AR42J acinar cells were pretreated with
      TNF-alpha to induce pancreatitis followed by 25 and 50 MUM pterostilbene for 15
      and 30 min. Secretion of lipase was quantified using a lipase assay and used as a
      marker of TNF-alpha-induced pancreatitis. Detection of STAT3, IL-1beta, and IL-6
      was performed using enzyme-linked immunosorbent assay. Analysis of variance and
      Tukey post hoc analysis were used for statistical analysis. RESULTS: TNF-alpha
      increased the secretion of lipase, IL-1beta, and IL-6. Pterostilbene treatment
      inhibited TNF-alpha-induced secretion of lipase (P<0.01 and P<0.001), IL-1beta
      (P<0.05), and IL-6 (P<0.05 and P<0.01). Inhibition of STAT3 by pterostilbene
      occurred with treatment doses of 25 and 50 MUM (P<0.001 and P<0.01). CONCLUSIONS:
      The dietary compound pterostilbene exerts an anti-inflammatory effect in
      pancreatitis through downregulation of STAT3 and decreased the secretion of
      lipase, IL-1beta, and IL-6. Pterostilbene's amelioration of pancreatitis in vitro
      makes it an advantageous anti-inflammatory agent. Further studies are necessary
      to determine pterostilbene's role as a protective or therapeutic agent in
      pancreatitis.

PMID- 22954524
TI  - Scientific impact of Association for Academic Surgery and Society of University
      Surgeons plenary session abstracts increases in the era of the Academic Surgical
      Congress from 2006 to 2010.
AB  - BACKGROUND: The objective of our study was to analyze plenary abstracts since
      2006, when the Association for Academic Surgery (AAS) and Society of University
      Surgeons (SUS) began hosting the combined annual Academic Surgical Congress
      (ASC). Plenary session abstracts from the separate AAS and SUS meetings from 2002
      to 2004 had previously revealed no significant difference in the scientific
      impact of published manuscripts. MATERIALS AND METHODS: In total, 76 abstracts
      from the AAS (n = 40) and SUS (n = 36) plenary sessions at the annual ASC
      meetings (2006-2010) were reviewed. Publication rate, citation number, 2010
      impact factor (IF), and 5-y IF were obtained. Statistical analysis was conducted
      using Fisher exact and Student t-tests. RESULTS: Overall, 60 (79%) of 76 ASC
      plenary abstracts presented between 2006 and 2010 were published in peer-reviewed
      journals. Analysis revealed a higher publication rate for AAS (90%) compared with
      SUS (67%) plenary abstracts (P = 0.02). Among the articles published, the overall
      mean number of total citations was 6.7, with no difference between AAS and SUS
      (5.9 versus 7.8, P = 0.46). The mean 2010 five-year IF for all publications was
      4.6 (AAS, 4.3 versus SUS, 5.0; P = 0.54). Compared with a previous analysis from
      the separate meetings, the mean IF has increased for both societies at an
      equivalent rate of 0.4. CONCLUSIONS: After the initiation of the joint ASC
      meeting in 2006, the SUS and AAS plenary presentations continue to exhibit high
      quality research. This study supports the benefit of a joint meeting for the AAS
      and SUS, as it has been associated with an increasing overall scientific impact
      for plenary abstracts.

PMID- 22954525
TI  - Meta-analysis of the risk for anastomotic leakage, the postoperative mortality
      caused by leakage in relation to the overall postoperative mortality.
AB  - BACKGROUND: Availability of anastomotic leakage rates and mortality rates
      following anastomotic leakage is essential when informing patients with rectal
      cancer preoperatively. We performed a meta-analysis of studies describing
      anastomotic leakage and the subsequent postoperative mortality in relation to the
      overall postoperative mortality after low anterior resection for rectal cancer.
      METHODS: A systematic search was performed of the published literature. Data on
      the definition and incidence rate of AL, postoperative mortality caused by AL,
      and overall postoperative mortality were extracted. Data were pooled and a meta
      analysis was performed. RESULTS: Twenty-two studies with 10,343 patients in total
      were analyzed. Meta-analysis of the data showed an average AL rate of 9%,
      postoperative mortality caused by leakage of 0.7% and overall postoperative
      mortality of 2%. The studies showed variation in incidence, definition and
      measurement of all outcomes. CONCLUSION: We found a considerable overall AL rate
      and a large contribution of AL to the overall postoperative mortality. The
      variability of definitions and measurement of AL, postoperative mortality caused
      by leakage and overall postoperative mortality may hinder providing reliable risk
      information. Large-scale audit programs may provide accurate and valid risk
      information which can be used for preoperative decision making.

PMID- 22954526
TI  - Validation over time of a nomogram including HER2 status to predict the sentinel
      node positivity in early breast carcinoma.
AB  - BACKGROUND: The molecular subtypes of breast cancer have different axillary
      status. A nomogram including the interaction covariate between estrogen receptor
      (ER) and HER2 has been recently published (Reyal et al. PLOS One, May 2011) and
      allows to identify the patients with a high risk of positive sentinel lymph node
      (SLN). The purpose of our study was to validate this model on an independent
      population. METHODS: We studied 755 consecutive patients treated at Institut
      Curie for operable breast cancer with sentinel node biopsies in 2009. The
      multivariate model, including age, tumor size, lymphovascular invasion and
      interaction covariate between ER and HER2 status, was used to calculate the
      theoretical risk of positive sentinel lymph node (SLN) for all patients. The
      performance of the model on our population was then evaluated in terms of
      discrimination (area under the curve AUC) and of calibration (Hosmer-Lemeshow HL
      test). RESULTS: our population was significantly different from the training
      population for the following variables: median tumor size in mm, lymphovascular
      invasion, positive ER and age. The nomogram showed similar results in our
      population than in the training population in terms of discrimination (AUC=0.72
      [0.68-0.76] versus 0.73 [0.7-0.75] and calibration (HL p=0.4 versus p=0.35).
      CONCLUSIONS: Despite significant differences between the two populations
      concerning variables which are part of the nomogram, the model was validated in
      our population. This nomogram is robust over time to predict the likelihood of
      positive SLN according to molecular subtypes defined by surrogate markers ER and
      HER2 determined by immunohistochemistry in clinical practice.

PMID- 22954527
TI  - Flexible graphene bio-nanosensor for lactate.
AB  - The development of a flexible nanosensor for detecting lactate could expand
      opportunities for using graphene, both in fundamental studies for a variety of
      device platforms and in practical applications. Graphene is a delicate single
      layer, two-dimensional network of carbon atoms with ultrasensitive sensing
      capabilities. Lactic acid is important for clinical analysis, sports medicine,
      and the food industry. Recently, wearable and flexible bioelectronics on plastics
      have attracted great interest for healthcare, sports and defense applications due
      to their advantages of being light-weight, bendable, or stretchable. Here, we
      demonstrate for the first time the development of a flexible graphene-based bio
      nanosensor to detect lactate. Our results show that flexible lactate biosensors
      can be fabricated on a variety of plastic substrates. The sensor can detect
      lactate sensitively from 0.08 MUM to 20 MUM with a fast steady-state measuring
      time of 2s. The sensor can also detect lactate under different mechanical bending
      conditions, the sensor response decreased as the bending angle and number of
      bending repetitions increased. We anticipate that these results could open
      exciting opportunities for fundamental studies of flexible graphene
      bioelectronics by using other bioreceptors, as well as a variety of wearable,
      implantable, real-time, or on-site applications in fields ranging from clinical
      analysis to defense.

PMID- 22954528
TI  - Single-labeled hairpin probe for highly specific and sensitive detection of
      lead(II) based on the fluorescence quenching of deoxyguanosine and G-quartet.
AB  - Specific and homogeneous detection of heavy metal ion is of great importance for
      both human health care and environmental protection. We reported a highly
      specific and sensitive assay for fluorescent detection of Pb(2+) based on the
      difference in quenching ability between deoxyguanosines and G-quartet by using
      carboxyfluorescein-labeled hairpin DNA (F-hpDNA) as a recognition probe. In the
      absence of target, the fluorescence of F-hpDNA can be quenched through
      photoinduced electron transfer from the dye to deoxyguanosines because the
      formation of hairpin brings deoxyguanosines close to the FAM. In the presence of
      Pb(2+), the formation of G-quadruplex DNA leads to a significant decrease in
      fluorescence due to the effective stack of dye on the G-quartet, which obviously
      intensified the quenching of fluorophore. In comparison with linear DNA probe,
      hairpin DNA probe greatly improved the specificity, and Pb(2+) can be highly
      selective detected even when coexisted with other metal ions. The quenching
      efficiency is linear with the concentration of lead(II) over the range of 0.5-500
      nM, with a limit of detection of 0.4 nM. Conformational switch from hairpin to G
      quadruplex was verified by CD measurements. Moreover, the application for
      detection of real samples further demonstrated its reliability. Therefore, it is
      a selective, simple and sensitive approach for detection of lead ion, as such, it
      promises to provide a solid foundation for developing universal analytical method
      for heavy metal ions.

PMID- 22954529
TI  - A label-free, impedance-based real time assay to identify drug-induced toxicities
      and differentiate cytostatic from cytotoxic effects.
AB  - Cell-based assays are key tools in drug safety assessment. However, they usually
      provide only limited information about time-kinetics of a toxic effect and
      implementing multiple measurements is often complex. To overcome these issues we
      established an impedance-based approach which is able to differentiate cytostatic
      from cytotoxic drugs by recording time-kinetics of compound-effects on cells. NIH
      3T3 fibroblasts were seeded on xCELLigence(r) E-plates and impedance was
      continuously measured over 5 days. The obtained results reflected cytotoxicity
      and cell proliferation, as confirmed by neutral red uptake in vitro. Based on
      known toxicants, we established an algorithm able to discriminate cytostatic,
      cytotoxic and non-toxic compounds based on the shape of the impedance curves.
      Analyzing impedance curve patterns of additional 37 compounds allowed the
      identification and differentiation of these distinct effects as results
      correlated well with previous in vivo findings. We show that impedance-based real
      time cell analysis is a convenient tool to characterize and discriminate effects
      of compounds on cells in a time-dependent and label-free manner. The presented
      impedance assay could be used to further characterize toxicities observed in vivo
      or in vitro. Due to the ease of performance it may also be a suitable screening
      tool.

PMID- 22954530
TI  - Evaluation of aggregating brain cell cultures for the detection of acute organ
      specific toxicity.
AB  - As part of the ACuteTox project aimed at the development of non-animal testing
      strategies for predicting human acute oral toxicity, aggregating brain cell
      cultures (AGGR) were examined for their capability to detect organ-specific
      toxicity. Previous multicenter evaluations of in vitro cytotoxicity showed that
      some 20% of the tested chemicals exhibited significantly lower in vitro toxicity
      as expected from in vivo toxicity data. This was supposed to be due to toxicity
      at supracellular (organ or system) levels. To examine the capability of AGGR to
      alert for potential organ-specific toxicants, concentration-response studies were
      carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression
      levels of four selected genes. The lowest observed effect concentration (LOEC)
      determined for each chemical was compared with the IC20 reported for the 3T3/NRU
      cytotoxicity assay. A LOEC lower than IC20 by at least a factor of 5 was taken to
      alert for organ-specific toxicity. The results showed that the frequency of
      alerts increased with the level of toxicity observed in AGGR. Among the chemicals
      identified as alert were many compounds known for their organ-specific toxicity.
      These findings suggest that AGGR are suitable for the detection of organ-specific
      toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay,
      improve the predictive capacity of in vitro toxicity testing.

PMID- 22954531
TI  - Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in
      human skin organ culture.
AB  - The increasing use of nano-sized materials in our environment, and in many
      consumer products, dictates new safety concerns. In particular, adequate
      experimental models are needed to evaluate skin toxicity of metal oxide ions,
      commonly found in cosmetic and dermatologic preparations. We have addressed the
      biological effects of topically applied copper oxide (CuO) nanoparticles in human
      skin organ cultures, using light and electron microscopy, and biochemical tests.
      Nanoparticles were more toxic than micro-sized particles, and their effects were
      stronger when supplied in growth medium than in topical application. Still
      topically applied CuO nanoparticles induced inflammatory cytokine secretion and
      necrosis, especially in epidermis deprived of its protective cornea. Since
      nanoparticle penetration was not seen, we propose that they may adhere to skin
      surface, react with the local acidic environment, and generate soluble ions that
      make their way to inner sites. This work illustrates the abilities of skin organ
      culture to evaluate the biological effects of topically-applied materials on skin
      in vitro.

PMID- 22954532
TI  - Attenuated effect of tungsten carbide nanoparticles on voltage-gated sodium
      current of hippocampal CA1 pyramidal neurons.
AB  - Nanomaterials and relevant products are now being widely used in the world, and
      their safety becomes a great concern for the general public. Tungsten carbide
      nanoparticles (nano-WC) are widely used in metallurgy, aeronautics and
      astronautics, however our knowledge regarding the influence of nano-WC on neurons
      is still lacking. The aim of this study was to investigate the impact of nano-WC
      on tetrodotoxin (TTX)-sensitive voltage-activated sodium current (I(Na)) of
      hippocampal CA1 pyramidal neurons. Results showed that acute exposure of nano-WC
      attenuated the peak amplitudes of I(Na) in a concentration-dependent manner. The
      minimal effective concentration was 10(-5)g/ml. The exposure of nano-WC
      significantly decreased current amplitudes of the current-voltage curves of I(Na)
      from -50 to+50 mV, shifted the steady-state activation and inactivation curves of
      I(Na) negatively and delayed the recovery of I(Na) from inactivation state. After
      exposure to nano-WC, the peak amplitudes, overshoots and the V-thresholds of
      action potentials (APs) were markedly reduced. These results suggested that
      exposure of nano-WC could influence some characteristics of APs evoked from the
      hippocampal CA1 neurons by modifying the kinetics of voltage-gated sodium
      channels (VGSCs).

PMID- 22954533
TI  - Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture.
AB  - Silver nanoparticles (AgNPs) are among the most widely commercialised engineered
      nanomaterials, because of their antimicrobial properties. They are already
      commonly used in medical devices, household products and industry. Concerns have
      been raised about potential adverse health effects due to increasing dispersion
      of AgNPs in the environment. The present study examined the cytotoxic effects of
      spherical, citrate-coated AgNPs (10, 50 and 100 nm) in rat brain endothelial
      (RBE4) cells and investigated whether the observed effects can be explained by
      the intrinsic toxicity of the particles or the silver ions released from the
      particles. The results indicated that exposure of RBE4 cells to AgNPs lead to
      significant reduction in dye uptake as measured with the Neutral red (NR) assay.
      The effect was found to be related to particle size, surface area, dose and
      exposure time. In contrast, silver ions increased NR uptake (ca. 10%) in RBE4
      cells after 1h, while a reduction in NR uptake was observed after 24h exposure at
      high concentrations (20-30 MUM). Colony formation, as an indicator of
      proliferation ability, was completely inhibited by AgNPs at concentrations higher
      than 1 MUg/ml. Silver ions had less effect on the colony formation of RBE4 cells
      than AgNPs.

PMID- 22954534
TI  - Bioluminescence based in vivo screening technologies.
AB  - Bioluminescence is the biologically active luminescence light producing event
      encountered in nature. In recent years several new screening methods utilizing
      bioluminescent cell-based biosensors have been designed demonstrating their
      utility towards dynamic monitoring of a variety of cellular functions. Because
      luciferase is unnatural to mammalian physiology, assays utilizing specific
      substrates to yield a luminescent signal are attractive and serve the purpose
      with high sensitivity and specificity. Often genetic or chemical modifications in
      different luciferase-substrate system in use have afforded new functionalities
      making these assays even more robust. Finally, in the evolving paradigm of
      molecular imaging, in vivo bioluminescence imaging (BLI) has evolved as a very
      attractive tool for interrogating human cellular biology in rodent models. In
      this short review we explore various bioluminescence screening strategies
      developed and analyze their scope in future drug screening processes.

PMID- 22954535
TI  - The "p word".

PMID- 22954536
TI  - Fear of flying.

PMID- 22954537
TI  - Point: Free-market solutions to an ongoing problem.

PMID- 22954538
TI  - Counterpoint: Someone has to pay.

PMID- 22954539
TI  - Healing images.

PMID- 22954540
TI  - Becoming a clinical diagnostic radiologist: the answer is not "clinically
      correlate".

PMID- 22954541
TI  - ACR Appropriateness Criteria(r) Suspected upper extremity deep vein thrombosis.
AB  - Upper-extremity venous thrombosis often presents as unilateral arm swelling. The
      differential diagnosis includes lesions compressing the veins and causing a
      functional venous obstruction, venous stenosis, an infection causing edema,
      obstruction of previously functioning lymphatics, or the absence of sufficient
      lymphatic channels to ensure effective drainage. The following recommendations
      are made with the understanding that venous disease, specifically venous
      thrombosis, is the primary diagnosis to be excluded or confirmed in a patient
      presenting with unilateral upper-extremity swelling. Contrast venography remains
      the best reference-standard diagnostic test for suspected upper-extremity acute
      venous thrombosis and may be needed whenever other noninvasive strategies fail to
      adequately image the upper-extremity veins. Duplex, color flow, and compression
      ultrasound have also established a clear role in evaluation of the more
      peripheral veins that are accessible to sonography. Gadolinium contrast-enhanced
      MRI is routinely used to evaluate the status of the central veins. Delayed CT
      venography can often be used to confirm or exclude more central vein venous
      thrombi, although substantial contrast loads are required. The ACR
      Appropriateness Criteria((r)) are evidence-based guidelines for specific clinical
      conditions that are reviewed every 2 years by a multidisciplinary expert panel.
      The guideline development and review include an extensive analysis of current
      medical literature from peer-reviewed journals and the application of a well
      established consensus methodology (modified Delphi) to rate the appropriateness
      of imaging and treatment procedures by the panel. In those instances in which
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging or treatment.

PMID- 22954542
TI  - The Moreton Lecture: Choices faced by radiology in the era of accountable health
      care.
AB  - If the United States is to address its overall economic challenges, the rate of
      growth of health care costs must be restrained. For the next decade, physicians
      should expect that the principal focus of health policy will be on cost
      reduction, with a particular emphasis on shifting the business model from one in
      which physicians and hospitals are rewarded for volume to a model in which they
      are accountable for value. To succeed in this new model, doctors will need to
      reduce overuse (driven primarily by overcapacity), eliminate the costs of
      preventable complications, and trim prices for many services. As radiologists
      (who are squarely in the center of these issues) face this future, they should
      take a leadership stance, help create effective accountable care systems, and set
      high aims for improvement. The alternatives--lapsing into victimhood, ceding
      design and leadership of accountable care to outside forces, and aiming for what
      is merely passable--are neither attractive nor professional.

PMID- 22954543
TI  - 2012 ACR Commission on Human Resources workforce survey.
AB  - PURPOSE: No reliable data exist to accurately track trends in the radiology
      workforce. To fill this void, the ACR Commission on Human Resources undertook an
      electronic survey to better understand the present workforce situation for
      radiologists. METHODS: The Practice of Radiology Environment Database((r)) of
      1,994 practices nationwide was used to identify practice leaders, who were asked
      to complete an electronic survey internally developed by the commission with the
      support of an outside consultant. The survey asked group leaders or their
      designates to report the number of radiologists they currently employ or
      supervise, the number hired in 2011, the number they plan to hire in 2012, and
      the number they plan to hire in 2014. Group leaders were asked to report
      subspecialty information for all radiologists in their practices. RESULTS: Twenty
      five percent of practice leaders (n = 504), corresponding to 31% of the total
      number of physicians practicing radiology or radiation oncology (n = 10,946),
      completed the survey. Practice leaders reported that 35% of the current workforce
      consists of general radiologists and 65% of specialists. Body imagers make up the
      largest category, followed by general interventional radiologists,
      neuroradiologists, and breast imagers. The results obtained allow a projection
      that approximately 1,241 radiologists were hired in 2011, 1,103 positions will be
      available in 2012, and 1,227 radiologists are expected to be hired in 2014.
      CONCLUSIONS: As a result of the data collected from the practices surveyed, it
      seems that there should be a job available for each of the 1,200 residents who
      complete their training programs each year, but the jobs may not necessarily be
      in the subspecialties, geographic areas, or types of practices that residents
      desire.

PMID- 22954544
TI  - Comparison of the 2006 and 2010 cardiac CT appropriateness criteria in a real
      world setting.
AB  - BACKGROUND: Coronary CT angiography (CCTA) is a relatively new technique whose
      role has yet to be fully defined. The initial appropriateness criteria (AC)
      guidelines published in 2006 have already been revised. There is paucity of data
      on the effect of the AC on the use of CCTA at academic centers and none for the
      private sector. METHODS: All CCTA studies ordered at one institution (a large
      community hospital with internal medicine and cardiovascular training programs)
      from 2006 to 2008 were retrospectively evaluated, and the ordering indications
      were categorized per the published AC for both 2006 and 2010. RESULTS: There were
      384 studies, of which 243 were included in this study. The majority of the
      studies were ordered for chest pain (67.1% of patients). A significant proportion
      of studies (43.2%) were classified as inappropriate on the basis of the 2006
      published criteria. Uncertain indications made up 39.1%, and appropriate
      indications were a minority. There was a significant regrading of appropriateness
      using the 2010 guidelines. Inappropriate testing remained similar at 48.1%, but
      uncertain cases decreased to only 2.8%, while appropriateness increased to 49.0%
      (P = .0001 for trend). CONCLUSIONS: The updated 2010 AC guidelines for CCTA
      resulted in a significant reclassification of the indications for ordering CCTA
      from the previous 2006 guidelines. This shift in the AC reflects increased
      familiarity and confidence with this new technology across the imaging community.
      A large proportion of CCTA studies were ordered for inappropriate indications
      using both sets of criteria. Further research and enhanced education are needed
      to disseminate the appropriate role of CCTA in cardiovascular imaging.

PMID- 22954545
TI  - Geographic and sociodemographic disparities in PET use by Medicare beneficiaries
      with cancer.
AB  - PURPOSE: PET use for cancer care has increased unevenly, possibly because of
      regional health care market characteristics or underlying population
      characteristics. The aim of this study was to examine variation in advanced
      imaging use among individuals with cancer in relation to population and hospital
      service area (HSA) characteristics. METHODS: A retrospective national study of
      fee-for-service Medicare beneficiaries with diagnoses of 1 of 5 cancers covered
      by Medicare for PET (2004-2008) was conducted. Crude and adjusted rates of PET,
      CT, and MRI were estimated for HSAs and sociodemographic subgroups. Generalized
      linear mixed models were used to assess the effects of race/ethnicity, area-level
      income, and HSA-level physician supply and spending on imaging utilization.
      RESULTS: On the basis of an annual average of 116,452 beneficiaries with cancer,
      adjusted PET rates (imaging days per person-year) showed significantly higher use
      for whites compared with blacks in both 2004 (whites, 0.35 [95% confidence
      interval, 0.34-0.36]; blacks, 0.31 [95% confidence interval, 0.30-0.33]) and 2008
      (whites, 0.64 [95% confidence interval, 0.63-0.65]; blacks, 0.57 [95% confidence
      interval, 0.55-0.59]). This trend was similar for the highest quartile of group
      level median household income but was opposite for CT use, with blacks having
      higher rates than whites. The highest Medicare-spending HSAs had significantly
      higher adjusted PET rates compared with lower spending areas (0.57 [95%
      confidence interval, 0.55-0.60] vs 0.69 [95% confidence interval, 0.67-0.71]
      imaging days/person-year). CONCLUSIONS: The use of PET among Medicare
      beneficiaries with cancer increased from 2004 to 2008, with higher rates observed
      among whites, among higher socioeconomic groups, and in higher Medicare spending
      areas. Sociodemographic differences in advanced imaging use are modality
      specific.

PMID- 22954546
TI  - The sharp reductions in medicare payments for noninvasive diagnostic imaging in
      recent years: will they satisfy the federal policymakers?
AB  - PURPOSE: The aim of this study was to examine recent trends in Medicare
      reimbursements for noninvasive diagnostic imaging (NDI). METHODS: The Medicare
      Part B databases for 2000 to 2010 were used. For each procedure code, these files
      provide payment and other data. All NDI codes were selected. Medicare physician
      specialty codes were used to identify radiologists, cardiologists, all other
      nonradiologist physicians as a group, and independent diagnostic testing
      facilities. Part B NDI payment trends were tracked. RESULTS: Overall Part B
      spending for NDI rose from $5.921 billion in 2000 to $11.910 billion in 2006
      (+101%). There was then a sharp drop in 2007, resulting from the implementation
      of the Deficit Reduction Act. This was followed by a slight rise in 2008, then
      successive smaller drops the next 2 years, reaching $9.457 billion in 2010 (-21%
      vs 2006). Radiologists' payments were $2.936 billion in 2000, rose to a peak of
      $5.3 billion in 2006 (+81%), then dropped to $4.712 billion in 2010 (-11% vs
      2006). Cardiologists' NDI payments were $1.327 billion in 2000, peaking at $2.998
      billion in 2006 (+126%), then dropping to $1.996 billion in 2010 (-33% vs 2006).
      Other physicians' payments were $1.106 billion in 2000, peaking at $2.378 billion
      in 2006 (+115%), then dropping to $1.968 billion in 2010 (-17% vs 2006). Similar
      trends occurred in independent diagnostic testing facilities. CONCLUSIONS: After
      years of rapid growth in Medicare NDI payments, an abrupt reversal occurred
      starting in 2007. By 2010, overall NDI costs to Medicare Part B were down 21%
      compared with their 2006 peak. It is unclear whether this large payment reduction
      will satisfy federal policymakers.

PMID- 22954547
TI  - Using the Internet for image transfer in a regional trauma network: effect on CT
      repeat rate, cost, and radiation exposure.
AB  - PURPOSE: The aims of this study were to evaluate an Internet-based and compact
      disc-based image transfer system and to compare this system with others in the
      literature, specifically regarding effects on repeat imaging rate, cost, and
      radiation dose to patients transferred to a level I regional trauma center.
      METHODS: Five hundred consecutive trauma patients transferred to a level I trauma
      center between June 1 and July 15, 2009, were included in the study. Images were
      transferred from an outside facility to the trauma center using the Internet and
      compact discs and uploaded to the trauma center's PACS. Radiographic studies and
      CT scans at the trauma center were classified as outside studies, completion
      studies, or repeat studies. Repeat rate, costs, and radiation doses of
      transferred and repeated CT scans were calculated. RESULTS: Four hundred ninety
      one patients met the inclusion criteria. The patients' average age was 40.5
      years, and 70% were men. The average Injury Severity Score was 14.7. Three
      hundred eighty-three patients had 852 CT studies and 380 nonextremity radiographs
      imported into the trauma center's PACS. At the trauma center, 494 completion CT
      scans and 2,924 radiographic studies were performed on these patients. Sixty-nine
      repeat CT scans were performed on 55 patients, equalling a 17% repeat rate. The
      total value of imported CT studies was $244,373.69. Repeat imaging totaled
      $20,495.95, or $84.65 per patient with transferred CT studies. CONCLUSIONS: Using
      a combination of the Internet and compact discs to transfer images during inter
      hospital transfer is associated with much lower repeat rates than those in the
      literature, suggesting that regional PACS networks may be useful for reducing
      cost and radiation exposure associated with trauma.

PMID- 22954548
TI  - Optimizing IVC filter utilization: a prospective study of the impact of
      interventional radiologist consultation.
AB  - PURPOSE: The use of inferior vena cava filters (IVCFs) is under increasing
      scrutiny because of device safety and economic considerations. The aim of this
      study was to test the hypothesis that interventional radiologist (IR)
      consultation results in better utilization of optional and permanent filters.
      METHODS: Over 6 months, an IVCF decision-making database at a single institution
      was prospectively studied. After IR consultation, each case was classified as
      concordant (agreement between the referring physician and the IR over filter
      choice) or discordant (disagreement over filter choice). The consulting IR
      estimated the likelihood of retrieval attempt for all optional filters at the
      time of placement (0%-100%). Chi-square and t tests were used for statistical
      analyses. The null hypotheses were rejected at P < .05. RESULTS: Sixty-six IVCFs
      (23 permanent, 43 optional) were placed in 66 patients. Sixteen of 66 decisions
      were discordant. In 7 of the 16 discordant cases, patients received optional
      filters; of these, 6 (86%) were declared permanent by the referring physician.
      For this group, the IR's prospective estimate of subsequent retrieval was 6.4%
      (0%-15%; P < .001). Fifty of 66 decisions were concordant. Of these, 36 patients
      received optional filters. Thirty-one of 36 concordant optional filters (86%)
      were successfully retrieved (P < .001). For this group, the IR's prospective
      estimate of subsequent retrieval was 88.3% (80%-100%; P < .001). Of the 5
      concordant devices not retrieved, 2 patients died, and 3 devices were declared
      permanent. There were no IVCF placement or retrieval failures. No patients were
      lost to follow-up. CONCLUSIONS: Interventional radiologists can prospectively
      predict the likelihood of optional filter retrieval. Significantly higher
      retrieval rates are achieved as a result of IR consultation. Interventional
      radiologist consultation positively affects IVCF device choice, patient safety,
      and effective utilization.

PMID- 22954549
TI  - When to embrace meaningful use?

PMID- 22954550
TI  - Retirement.

PMID- 22954551
TI  - The challenging case conference: initial observations and feedback.

PMID- 22954552
TI  - Understanding CT dose display.

PMID- 22954553
TI  - William D. Coolidge.

PMID- 22954554
TI  - Ontogenic changes in human placental sodium iodide symporter expression.
AB  - The human fetus requires a maternal supply of iodide to synthesize thyroid
      hormone from 16 weeks gestation. Placental iodide transport is regulated by the
      sodium iodide symporter (NIS). We studied the ontogeny of NIS in placentas from
      surgically terminated pregnancies and from normal term pregnancies. NIS mRNA was
      low at 6 weeks gestation and peaked at 12 weeks gestation. Placental NIS protein
      levels are significantly correlated with gestational age during early pregnancy
      and increase with increased placental vascularization. This would lead to
      increased iodide supply to meet increased fetal requirements for thyroid hormone
      synthesis as the pregnancy progresses.

PMID- 22954555
TI  - Increased femoral cartilage thickness in patients with Klinefelter syndrome.
AB  - The objective of this study was to determine femoral cartilage thickness (FCT) in
      patients with Klinefelter syndrome (KS), which is the most common sex chromosome
      disorder in men with varying degrees of androgen deficiency. This cross-sectional
      controlled study was conducted in a tertiary care center. Participants were 33
      male patients (mean age = 36.2 years) with KS and 35 aged-matched healthy male
      controls (mean age = 32.9 years). Femoral condyle cartilage was measured by
      ultrasonography at three locations in each knee. Total testosterone, estradiol,
      sex hormone binding globulin, free androgen index, bioavailable testosterone, and
      albumin levels were measured. Femoral cartilage of patients at right and left
      knee lateral (3.03 and 2.99 mm), mid (3.81 and 3.74 mm), and medial (3.01 and
      3.20 mm) were statistically thicker than in controls (right and left knee lateral
      2.29 and 2.36 mm, mid 2.64 and 2.53 mm, medial 2.39 and 2.32 mm, respectively, p
      < .001). There was no significant correlation between FCT and sex hormones. In
      conclusion, patients with KS had thicker femoral cartilage. Relatively low
      testosterone levels in these patients and altered estrogen metabolism may
      hypothetically explain increased cartilage thickness in these patients.

PMID- 22954556
TI  - Talking about sexuality: desire, virility, and intimacy in the context of
      prostate cancer associations.
AB  - Prostate cancer and its outcomes are a real threat for health and well-being for
      men living in the Western world. The number of men with a diagnosis of prostate
      cancer, before the age of 65 years, has increased in recent decades. The aim of
      this study was to explore how some of these Swedish men experienced and talked
      about their sexuality. Four focus group discussions were performed in the context
      of associations for prostate cancer. Using qualitative content analysis, it was
      identified how the diagnosis was a threat to their male identity; the men's
      vulnerability as a group in society was made explicit. Their sexuality was
      diminished by their illness experiences. These experiences were difficult to
      share and talk about with others and therefore connected with silence and sorrow.
      As a result of this, the informants often played a passive role when or if they
      discussed issues related to sexuality with someone in the health care
      organizations. The possibility of voluntarily joining a cancer association was
      probably highly beneficial for these men. During the sessions, several men
      expressed the opinion that "it is always great to talk."

PMID- 22954557
TI  - Exercise effects on two men with fibromyalgia syndrome: an update.
AB  - In 2007, an article was published in this journal about the effects of exercise
      on two older men with fibromyalgia syndrome (FMS). This new article is an update
      on how exercise has affected them during a 4-year period since 2007. Results
      suggest that both these men still function at approximately the same levels
      (physically and psychosocially) as reported in 2007. This is viewed as a positive
      finding, because even with all of their FMS symptoms, these two men managed to
      maintain their functional capacity. It is hard for most older people without FMS
      to remain motivated enough to accomplish this. Because it is difficult to find
      specifically published data on men (vs. women) with FMS, this long-term
      information on these two men is important for professionals who are involved in
      exercise programming for men with FMS and for those interested in studying
      exercise effects on men with FMS.

PMID- 22954558
TI  - Overall health and health care utilization among Latino American men in the
      United States.
AB  - Although the Latino American male population is increasing, the subgroup Latino
      men's health remains underinvestigated. This study examined the overall pattern
      of Latino male health and health care utilization in major subgroups, using a
      nationally representative sample (N = 1,127) from the National Latino and Asian
      American Study. The authors evaluated rates of chronic, behavioral, and mental
      health service utilization in this first nationally representative survey. The
      results identified significant cross-subgroup differences in most physical and
      chronic conditions with Puerto Rican American men having high rates in 8 of 15
      physical ailments, including life-altering conditions such as cardiovascular
      diseases. Despite differences in racial/ethnic, socioeconomic, and cultural
      factors, Cuban American men shared similar rates of heart diseases and cancer
      with Puerto Rican American men. In addition, Puerto Rican American men had higher
      rates of substance abuse than other Latinos. For health providers, the authors'
      findings encourage awareness of subgroup differences regarding overall health
      issues of Latino American men to provide culturally appropriate care.

PMID- 22954559
TI  - What you can't see can hurt you!

PMID- 22954560
TI  - Appropriate timing of nitroglycerin prior to intravascular ultrasound.
AB  - OBJECTIVES: To determine the time to maximal coronary dilation following
      intracoronary (IC) nitroglycerin (NTG) and whether the decrease in aortic
      pressure (AoP) is a surrogate marker for coronary vasodilatation. BACKGROUND:
      Intravascular ultrasound (IVUS) facilitates assessment of coronary plaque
      severity and morphology and aids in stent sizing. NTG is often administered prior
      to IVUS to prevent catheter-induced spasm and to facilitate standardized and
      accurate vessel size measurements. The impact of dose, timing, and route of
      delivering NTG on vessel size remains undefined. METHODS: Twelve patients
      undergoing IVUS-guided stent placement were studied. An IVUS catheter was
      positioned proximal to the target lesion and the following measurements made at
      baseline and 30 second (sec) intervals for 180 sec following 200 mcg IC NTG: AoP,
      IVUS-derived lumen diameter (Ld), lumen cross-sectional area (La), external
      elastic membrane diameter (EEMd) and EEM area (EEMa). Lumen and EEM measurements
      were compared at different time intervals and the relationship between time to
      max Ld and nadir AoP was analyzed. RESULTS: All patients had a vasodilatory
      response to IC NTG. Increase from baseline to max Ld following IC NTG was
      statistically significant (mean change 0.31 +/- 0.18 mm, P=.0001). Mean time to
      max Ld following IC NTG was 117 sec (range, 60-180 sec). No correlation between
      time to max Ld and AoP nadir was observed (r = 0.19). CONCLUSIONS: Our study
      suggests that administration of 200 mcg IC NTG results in a significant change in
      lumen diameter and area with maximal vasodilation occurring on average
      approximately 2 minutes following IC NTG administration. There was no significant
      correlation between AoP change and maximal NTG-induced coronary vasodilation.

PMID- 22954561
TI  - Impact of chronic total coronary occlusion on microvascular reperfusion in
      patients with a first anterior ST-segment elevation myocardial infarction.
AB  - BACKGROUND: We investigated an impact of the presence of chronic total coronary
      occlusion (CTO) in a non-infarct related coronary artery on microvascular
      reperfusion in patients with a first anterior ST-segment elevation myocardial
      infarction (STEMI) who underwent percutaneous coronary intervention (PCI).
      METHODS: In accordance with the presence or absence of CTO in a non-infarct
      related coronary artery, we analyzed Thrombolysis in Myocardial Infarction
      myocardial perfusion (TMP) grade on a scale of 0 to 3, with higher scores
      indicating better perfusion, and ST-segment resolution in sum of lead I, aVL, and
      V1 through V6 to evaluate microvascular reperfusion in a total of 140 consecutive
      patients with a first anterior STEMI. RESULTS: We identified CTO in 15 patients
      (11% of total). The incidence of impaired microvascular reperfusion was greater
      in patients with CTO vs without CTO, defined as TMP grades 0 or 1 together with
      <30% ST-segment resolution (33% vs 6%, respectively; P=.0006) and the enzymatic
      infarct was larger (10304 +/- 8060 IU/L vs 6804 +/- 4959 IU/L; P=.009). Logistic
      regression analysis revealed that CTO is closely associated with incidental
      impaired microvascular reperfusion (odds ratio, 6.801; 95% confidence interval,
      1.284-36.209; P=.024). CONCLUSION: The presence of CTO in a non-infarct related
      coronary artery might confer a considerable disadvantage upon microvascular
      reperfusion and result in adverse clinical outcomes of PCI for a first anterior
      STEMI.

PMID- 22954562
TI  - Analyzing the failures of percutaneous closure of the patent ductus arteriosus in
      patients over 5 kg.
AB  - Percutaneous closure of the patent ductus is the gold standard therapy. Our aim
      was to analyze our failures between 2001 and 2010. METHODS: All patients over 5
      kg benefited from a transcatheter attempt at duct closure. Coils and Amplatzer
      duct occluder (ADO) I were used before 2008, and ADO I and ADO II afterward. The
      failure was recovered when another percutaneous attempt was successful and
      definite when surgery was needed. RESULTS: There were 138 patients. Coils were
      used in 22 patients (16%), ADO I in 74 (54%), and ADO II in 42 (30%). Immediate
      and 6-month closure rates were 55% and 100% for coils, 40% and 96% for the ADO I,
      and 74% and 93% for the ADO II, respectively. There were no failures in the coil
      group, and 3 failures in each of the ADO I and ADO II groups. Among the 3 ADO I
      failures, 1 was recovered after device migration into the abdominal aorta. The 2
      other failures were definite, due to immediate device protrusion, once in the
      aorta and once in the pulmonary artery. One of the 3 ADO II failures was
      definite, due to protrusion into the aorta, 10 days following the procedure. The
      two other failures were due to immediate device migration into the pulmonary
      artery, and were both recovered. CONCLUSIONS: 97% of ducts can be closed
      percutaneously. The combination of coil and ADO I gives excellent results. Failed
      attempts with the ADO II were bailed out by the ADO I.

PMID- 22954563
TI  - Sodium bicarbonate for the prevention of contrast-induced nephropathy: the
      efficacy of high concentration solution.
AB  - BACKGROUND: The appropriate dose of sodium bicarbonate to prevent contrast
      induced nephropathy (CIN) has not been established. METHODS AND RESULTS: To
      determine the efficacy of high-concentration sodium bicarbonate, 123 consecutive
      patients with renal dysfunction undergoing coronary angiography with/without
      intervention were administrated either high-concentration (group H: 833 mEq/L, n
      = 87) or low-concentration (group L: 160 mEq/L, n = 36) sodium bicarbonate at the
      rate of 3 mL/kg/h for 1 hour before the contrast exposure, and followed by 1
      mL/kg/h for 7 hours. A total of 77 patients (group H, n = 54; group L, n = 23)
      without prophylactic continuous hemodiafiltration were analyzed in this study.
      Urine pH (n = 10 for each group and n = 5 for control) was increased by
      concentration and time-dependent manner in each group. Urine pH at 3 hours after
      administration of sodium bicarbonate was significantly higher in group H than
      group L and control (8.50 +/- 0.94 vs 6.95 +/- 1.17 vs 5.70 +/- 0.97,
      respectively; P<.001). Incidence of CIN (0% vs 17.3%; P=.005) was lower in group
      H than group L. Percent change in creatinine within 48 hours was significantly
      lower in group H than group L (-2.65 +/- 9.83% vs 9.14 +/- 14.0%; P=.001).
      Percent change in estimated glomerular filtration rate within 48 hours was
      significantly higher in group H than group L (3.97 +/- 11.8 vs -7.43 +/- 13.3;
      P<.001). CONCLUSION: Administration of a higher concentration of sodium
      bicarbonate was more effective for urine alkalization and prevention of CIN.

PMID- 22954564
TI  - Mid-term results of everolimus-eluting stent in a Japanese population compared
      with a US randomized cohort: SPIRIT III Japan Registry with harmonization by
      doing.
AB  - To address safety concerns with first-generation drug-eluting stents (DESs), the
      everolimus-eluting stent (EES) has been developed as a second-generation DES. The
      study aim was to: (1) demonstrate that use of the EES in Japanese patients is non
      inferior to use of the paclitaxel-eluting stent (PES) in US patients; and (2)
      compare vessel response to the EES in Japanese vs US patients. METHODS: The
      SPIRIT III Japan Registry, a prospective single-arm multicenter study was a part
      of the SPIRIT III global clinical program using harmonization by doing. The
      primary endpoint was in-segment late loss at 8 months, compared to US PES.
      RESULTS: A total of 88 subjects were enrolled in the Japan EES group.
      Angiographic in-segment late loss was significantly less in Japan EES vs US PES
      (0.15 +/- 0.34 mm vs 0.28 +/- 0.48 mm, respectively; P=.0185; Pnon-inferio
      r<.0001), while target vessel failure (TVF; 8.0% vs 9.9%) and major adverse
      cardiac events (MACE) at 9 months (5.7% vs 8.8%) were not significantly different
      between the 2 groups. No differences were observed between Japan and US EES
      populations in terms of late loss, TVF, or MACE. Neointimal volume and
      postprocedural incomplete stent apposition rate were lower in Japan EES vs US
      EES/PES. CONCLUSION: The SPIRIT III Japan Registry met the primary endpoint of
      lower late loss in the Japan EES group vs the US PES group, with comparable
      results for EES between the Japanese and US patients.

PMID- 22954565
TI  - A novel approach for transcoronary pacing in a porcine model.
AB  - BACKGROUND: Transcoronary pacing for the treatment of bradycardias during
      percutaneous coronary intervention (PCI) is a useful technique in interventional
      cardiology. The standard technique is unipolar pacing with the guidewire in the
      coronary artery against a cutaneous patch electrode. We developed a novel
      approach for transcoronary pacing by using intravascular electrodes in different
      positions in the aorta in a porcine model. METHODS AND RESULTS: Unipolar
      transcoronary pacing was applied in 8 pigs under general anesthesia using a
      standard floppy guidewire in a coronary artery as the cathode with additional
      insulation of the guidewire by a monorail angioplasty balloon. Intravascular
      electrodes positioned in the aorta thoracalis and the aorta abdominalis served as
      indifferent anodes. The efficacy of transcoronary pacing with intravascular
      anodal electrodes was assessed by measurement of threshold and impedance data and
      the magnitude of the epicardial electrogram in comparison to unipolar transvenous
      pacing using the same indifferent anodal electrodes. Transcoronary pacing with
      the guidewire-balloon combination using indifferent intravascular electrodes was
      effective in all cases. Transcoronary pacing thresholds obtained against the
      indifferent coil electrodes in the aorta thoracalis (0.8 +/- 0.5 V) and in the
      aorta abdominalis (0.8 +/- 0.5 V) were similar to those obtained with unipolar
      transvenous pacing (0.7 +/- 0.3 V and 0.6 +/- 0.2 V, respectively), whereas the
      tip-electrode in the aorta thoracalis serving as indifferent anode produced
      significantly higher pacing thresholds (guidewire, 2.8 +/- 2.6 V; transvenous
      lead, 1.5 +/- 0.8 V). The lower pacing threshold of the coil-electrodes was
      associated with significantly lower impedance values (aorta thoracalis, 285 +/-
      63 ohm; aorta abdominalis, 294 +/- 61 ohm) as compared to the tip-electrode in
      the aorta thoracalis (718 +/- 254 ohm). The amplitude of the epicardial
      electrogram acquired by the intracoronary guidewire was without significant
      differences between the indifferent electrodes. CONCLUSIONS: Transcoronary pacing
      in the animal model using a standard guidewire with balloon insulation and
      intravascular indifferent electrodes is depending on the optimal configuration of
      the anodal electrode. The use of intravascular coil electrodes with a sufficient
      surface area can produce 100% capture at thresholds comparable to transvenous
      pacing. Therefore, technical integration of these coil electrodes into the access
      sheath or the guiding catheter with respect to handling these tools in daily
      clinical practice in the catheterization laboratory could further facilitate the
      transcoronary pacing approach.

PMID- 22954566
TI  - Second valve implantation for the treatment of a malpositioned transcatheter
      aortic valve.
AB  - BACKGROUND: Unfavorable immediate or delayed results after transcatheter aortic
      valve implantation (TAVI) may be a consequence of bioprosthesis malfunctioning,
      malpositioning, embolization, or degeneration. Deployment of a second valve
      within the first one implanted (TAVI-in-TAV) may be a potentially helpful
      therapeutic strategy. METHODS: Six out of 412 patients undergoing TAVI had TAVI
      in-TAV implantation for the treatment of a too high (n = 4) or too low position
      (n = 2) of the first implanted valve. RESULTS: All TAVI-in-TAV procedures were
      successfully performed. The calculated valve area after second valve implantation
      was 1.6 +/- 0.3 cm(2) with a mean gradient of 7.3 +/- 2.2 mm Hg. Residual aortic
      regurgitation (AR) was mild in 5 patients and moderate in 1. At mid-term follow
      up (30-724 days) neither the mean valve area (1.47 +/- 0.31 cm(2)), the mean
      gradient (7.5 +/- 3.6 mm Hg; 3.0-13.0 mm Hg) nor the degree of AR had changed
      significantly. CONCLUSION: TAVI-in-TAV for correction of malpositioned or
      embolized valves is technically feasible and leads to favorable functional
      results during mid-term follow-up.

PMID- 22954567
TI  - Peri-aortic hematoma complicated with aortic regurgitation following
      transcatheter aortic valve implantation: description of a novel mechanism of
      paravalvular leak.
AB  - The recent development of transcatheter aortic valve implantation (TAVI) for
      patients with severe aortic stenosis (AS) offers a feasible option for high-risk
      surgical patients. However, several complications are specifically related to
      this technique. The present case describes a novel complication associated with
      TAVI, a severe paravalvular leak related to "stretch-induced" peri-aortic
      hematoma. The possible mechanisms of this complication, as well as its potential
      solutions, are discussed.

PMID- 22954568
TI  - Treatment of coronary aneurysms with covered stents: a review with illustrated
      case.
AB  - Coronary aneurysms are found in approximately 5% of patients undergoing coronary
      angiography. Most coronary artery aneurysms (CAAs) are associated with
      significant stenosis of the coronary lumen; however, there is no common consensus
      on the treatment of coronary aneurysms. A large aneurysm in the coronary artery
      makes the blood flow turbulent and predisposes to thrombus formation and coronary
      artery obstruction even without the presence of significant stenosis. Despite
      this important anatomical abnormality of the coronary artery, the treatment
      options are poorly understood and present a therapeutic challenge to the
      interventional cardiologist. While treating CAAs with percutaneous implantation
      of covered stents offers a less invasive option compared to surgical correction,
      the short- and long-term outcomes are unknown. In this article, we have reviewed
      the literature and discussed the pathophysiology, clinical importance, and
      treatment options for CAAs. The illustrated case demonstrates a difficult
      situation in the management of CAA with interesting images, including coronary
      angiography, intravascular ultrasound, and transesophageal echocardiography of
      the complication encountered in this particular case.

PMID- 22954569
TI  - Entrapment of a looped/kinked catheter in the brachial artery and its successful
      retrieval during transradial coronary catheterization.
AB  - Transradial access for cardiac catheterization is widely accepted as a safe and
      viable approach with markedly decreased incidence of major accessrelated
      complications compared to the transfemoral approach. Minor catheter looping or
      kinking during catheter manipulation is common and can be managed with gentle
      rotation, and thus goes unnoticed without complications. Rarely, this
      looped/kinked catheter can get entrapped and require an invasive approach for
      retrieval. To our knowledge, there is only one such case described for the
      transradial approach, where the authors had to use a 6 Fr Amplatz gooseneck snare
      kit via right femoral approach to remove the entrapped catheter. We present a
      case of entrapped looped/kinked 5 Fr catheter during transradial catheterization
      in the brachial artery and describe a novel approach of removing this entrapped
      catheter through the same radial access without any complications.

PMID- 22954570
TI  - Intracardiac echocardiography to guide percutaneous closure of atrial baffle
      defects.
AB  - BACKGROUND: Patients with complex congenital heart disease may require surgical
      construction of interatrial baffles to shunt blood between atria. Long-term
      complications of these procedures may include stenosis or leak of the baffle,
      typically along the suture line. There are limited data on transcatheter
      management and intraprocedural imaging of these anatomically complex lesions.
      METHODS: We describe three cases of adults who each presented with baffle leaks
      more than 20 years after surgical construction of an atrial baffle. In each case,
      intracardiac echocardiography was essential for intraprocedural guidance, sizing
      of the defect, and successful percutaneous deployment of an Amplatzer septal
      occluder device to close the baffle leak. RESULTS AND CONCLUSIONS: One patient
      had a baffle leak along the inferior surface of the baffle suture line; the
      second patient had a baffle leak along the superior border with the left atrium;
      the third patient had a leak along the sutures of surgical shunt for an anomalous
      pulmonary vein. Percutaneous closure was successful in all cases, with deployment
      of an Amplatzer occluder device in each case. Intracardiac echocardiography may
      be may be useful for procedural guidance during percutaneous closure of atrial
      baffle defects.

PMID- 22954571
TI  - Intracoronary dehiscence of radiopaque ring of a guiding catheter and its
      retrieval.
AB  - Intracoronary dehiscence of the radiopaque ring of a guiding catheter is a rare
      complication, which could lead to myocardial infarction, emergency surgery, or
      even death. We describe the percutaneous retrieval of the catheter material from
      the right coronary artery, thus avoiding surgery and related complications.

PMID- 22954572
TI  - Successful percutaneous coronary intervention of an anomalous right coronary
      artery with high anterior takeoff using a DIO thrombus aspiration catheter.
AB  - Selecting an appropriate guiding catheter is the most important determinant of
      procedural percutaneous coronary intervention success, especially with an
      anomalous right coronary artery with high anterior takeoff, which is rather
      complicated. We present a case of successful stent implantation in an anomalous
      right coronary artery with high anterior takeoff using DIO thrombus aspiration
      catheter. This method is useful when selection of the guiding catheter is rather
      complicated such as in the case of congenital coronary anomalies.

PMID- 22954573
TI  - Myocardial infarction caused by ostial right coronary artery thrombus in the
      absence of atheromatosis.
AB  - Myocardial infarction in patients with normal coronary vessels is a relatively
      rare entity that is observed in up to 2.8% of patients with myocardial
      infarction. In this case, we present a patient in whom presence of thrombus was
      suspected by pressure damping during engagement of the right coronary ostium
      despite the normal angiographic morphology. Further contrast injections with the
      catheter resting outside the ostium and intravascular imaging with optical
      coherence tomography helped confirm the suspicion of ostial thrombosis, as well
      as the presence of non-atheromatic vascular wall. The patient was consequently
      treated with thrombus aspiration and stenting of the vessel ostium.

PMID- 22954574
TI  - Takayasu arteritis: use of drug-eluting stent and balloon to treat recurring
      carotid restenosis.
AB  - Takayasu arteritis (TA) is an inflammatory disease affecting large and medium
      sized arteries and causing occlusive, aneurysmal, or stenotic lesions. It is also
      known that with chronic course, the disease has a tendency to recur at either the
      same site or different. We report a patient with TA whose carotid stenosis was
      initially treated with bare metal stents but the patient suffered from recurring
      localized restenosis. Eventually, the patient was treated with (off-label)
      coronary drug-eluting stent and drug-eluting balloon with favorable long-term
      outcome. Therefore, we suggest that drug-eluting interventions might have a place
      in treatment of TA patients with recurring restenosis.

PMID- 22954575
TI  - Spontaneous coronary artery dissection in an elderly woman presenting with chest
      pain and positive cardiac biomarkers.
AB  - A 68-year-old African American female with a prior medical history of
      hypertension and dyslipidemia presented with sudden onset pressure-like
      substernal chest pain. Initial ECG showed no ST or T wave abnormalities, and
      troponin elevation of 2.88 ng/mL. Two hours later, chest pain recurred with ECG
      change and increase in troponin to 11.97 ng/mL. She underwent urgent coronary
      angiography, which revealed left anterior descending artery dissection with
      thrombus. We successfully treated with balloon angioplasty followed by placement
      of 3 drug-eluting stents resulting in TIMI-3 flow; further testing for vasculitis
      was negative. Once spontaneous coronary artery dissection is diagnosed, the
      approach to treatment is controversial and treatment should be patient tailored.

PMID- 22954576
TI  - The power of collateral circulation: a case of asymptomatic chronic total
      occlusion of the left main coronary artery.
AB  - Total occlusion of the left main coronary artery predominantly presents with
      recurrent angina or myocardial infarction. Long-term survival and myocardial
      function depends on the well-developed right to left collaterals. We report a
      case of a 46-year-old man who was referred because of incidental finding of low
      ejection fraction during work-up for syncope 5 months prior. The patient denied
      any recurrence or any other symptom after that episode and claimed an unchanged
      exercise capacity. He had hypertension, hyperlipidemia, and history of 15
      pack/year smoking. Except for class II morbid obesity, he had completely normal
      vital signs, physical examination, and lab tests on admission. The echocardiogram
      was suggestive of previous anterior wall myocardial infarction and demonstrated a
      low left ventricle ejection fraction with diffuse hypokinesis of the left
      ventricle. The patient underwent cardiac catheterization, which revealed total
      occlusion of the left main coronary artery, dominant right coronary artery with a
      95% stenosis in the proximal segment, and collaterals from the right to the left
      coronary arteries. The patient was immediately referred for coronary artery
      bypass surgery. This case demonstrates the power of collateral circulation in
      protecting the patient from symptoms and death despite total occlusion of the
      left main coronary artery and severe stenosis of the proximal right coronary
      artery.

PMID- 22954577
TI  - Successful delivery of polytetrafluoroethylene-covered stent through 5 French
      guiding catheter.
AB  - Deployment of a polytetrafluoroethylene-covered stent is a useful option to seal
      coronary perforation. However, the high profile and low flexibility compromise
      its deliverability. To facilitate stent delivery, deep-vessel intubation with a 5
      Fr guiding catheter through a 6 or 7 Fr guiding catheter (mother-and-child
      catheter) has been used. This case report describes a successful deployment of a
      polytetrafluoroethylene-covered stent through a 5 Fr Heartrail ST01 guiding
      catheter (Terumo) to seal coronary perforation.

PMID- 22954578
TI  - Percutaneous pulmonary valve implantation in left pulmonary artery branch in a
      patient with a functional single lung.
AB  - Percutaneous pulmonary valve technology has had a great impact on patients with
      congenital and acquired heart disease. In some patients, implantation of a
      percutaneous pulmonary valve may not be possible due to the morphology of the
      existing right ventricular outflow tract. In this report, we describe
      implantation of a Melody transcatheter pulmonary valve in the left pulmonary
      artery in a patient with acquired right pulmonary artery occlusion and a large
      right ventricular outflow tract.

PMID- 22954579
TI  - Novel method of rescuing kinked guide catheter from axillary artery in
      transradial coronary intervention: the balloon retrieval technique.
AB  - This case illustrates a novel and innovative method of retrieving a kinked
      guiding catheter in transradial intervention without the need for vascular snare.

PMID- 22954580
TI  - An interventional percutaneous approach of posttraumatic left coronary artery
      fistula repair.
AB  - We present an interesting case on the management of a traumatic coronary artery
      fistula in a 39-year-old man who was stabbed by his wife. During emergency
      sternotomy, left lung and right ventricle injuries were repaired. On the second
      postoperative day, an acute myocardial infarction of the anterior wall was
      recognized. Coronary angiography revealed a rare case of a fistula between the
      left anterior descending coronary artery and the right ventricle of the heart,
      which was treated by a stent-graft to avoid a re-operation.

PMID- 22954582
TI  - [Takotsubo: nature of emotional stress].

PMID- 22954581
TI  - Competition and compensation: dissecting the biophysical and functional
      differences between the class 3 myosin paralogs, myosins 3a and 3b.
AB  - Stereocilia are actin protrusions with remarkably well-defined lengths and
      organization. A flurry of recent papers has reported multiple myosin motor
      proteins involved in regulating stereocilia structures by transporting actin
      regulatory cargo to the tips of stereocilia. In our recent paper, we show that
      two paralogous class 3 myosins--Myo3a and Myo3b--both transport the actin
      regulatory protein Espin 1 (Esp1) to stereocilia and filopodia tips in a
      remarkably similar, albeit non-identical fashion. (1) Here we present
      experimental and computational data that suggests that subtle differences between
      these two proteins' biophysical and biochemical properties can help us understand
      how these myosin species target and regulate the lengths of actin protrusions.

PMID- 22954583
TI  - Minimal disease activity in Gaucher disease: criteria for definition.
AB  - Gaucher disease type I is a metabolic disorder caused by a genetic deficiency of
      lysosomal beta-glucocerebrosidase that leads to accumulation of glucocerebroside
      in macrophages, thus causing damage in different organ systems. Enzyme
      replacement therapy with imiglucerase improves organ impairment and clinical
      manifestations, but patients differ in response to treatment. While clinical
      remission is the most desirable therapeutic outcome, a more realistic goal in
      patients with high disease burden is reasonably good clinical status despite
      persistence of residual biochemical or imaging abnormalities. Therefore, the
      concept of minimal disease activity--used in certain haematological or
      rheumatologic conditions--needs to be introduced in Gaucher disease, with a level
      of disease activity that patients and physicians consider a useful treatment
      target. In this paper, we propose specific parameters and criteria for defining
      minimal disease activity in Gaucher disease and its stability over time, based on
      three major systemic domains typically involved: haematological, visceral, and
      skeletal. Biomarker parameters were not included as criteria, because currently
      they do not adequately reflect disease evolution in individual patients.
      Neurological and respiratory domains were also excluded, as their involvement per
      se indicates severe disease unlikely to respond to enzyme replacement therapy and
      achieve minimal disease status. Our goal in defining minimal disease activity and
      stability is to identify a tool to facilitate treatment decisions in clinical
      practice.

PMID- 22954584
TI  - A microfluidic system for long-term time-lapse microscopy studies of
      mycobacteria.
AB  - Phenotypic heterogeneity in bacterial populations is thought to contribute to a
      number of important phenomena including sporulation and persistence. The latter
      has clinical implications in many diseases such as tuberculosis, where
      persistence of Mycobacterium tuberculosis within the human host is believed to be
      the root cause of latent tuberculosis and the ability of a minority population of
      cells to survive antibiotic exposure, despite being genetically identical to the
      bulk population that are killed. However, phenotypic variations caused by non
      genetic mechanisms are difficult to study because of the transient nature of the
      persistent state and thereby the requirement to observe individual cells in real
      time. Recently, microfluidics, combined with time-lapse microscopy, has become a
      powerful tool for studying population heterogeneity in bacteria. However, growth
      and replication of mycobacterial cells provide particular problems for the
      development of microfluidic systems due to their tendency to grow in three
      dimensions. We here describe a novel microfluidic device for the observation of
      growth and antibiotic killing in individual mycobacterial cells. We constructed a
      microfluidic device suitable for studying single cell behavior in mycobacteria.
      The growth of single cells of Mycobacterium smegmatis expressing green
      fluorescent protein was monitored using a confocal laser scanning microscope.
      Within the device M. smegmatis cells were tightly confined within a hydrogel
      matrix thus promoting planar growth. Cell growth and killing was observed in the
      device with dead cells highlighted by uptake of propidium iodide.
      Conclusions/Significance. We demonstrate that our device allows real-time
      analysis and long-term culture of single cells of mycobacteria, and is able to
      support the study of cell death during the application of antibiotics. The device
      will allow observation of individual cells' cell genealogy to be determined and
      direct observation of rare states, such as persistence.

PMID- 22954585
TI  - Evaluation of CoA biosynthesis proteins of Mycobacterium tuberculosis as
      potential drug targets.
AB  - Coenzyme A biosynthesis pathway proteins are potential targets for developing
      inhibitors against bacteria including Mycobacterium tuberculosis. We have
      evaluated two enzymes in this pathway: phosphopantetheine adenylyltransferase
      (CoaD) and dephospho CoA kinase (CoaE) for essentiality and selectivity. Based on
      the previous transposon mutagenesis studies, coaD had been predicted to be a non
      essential gene in M. tuberculosis. Our bioinformatics analysis showed that there
      is no other functional homolog of this enzyme in M. tuberculosis, which suggests
      that coaD should be an essential gene. In order to get an unambiguous answer on
      the essentiality of coaD, we attempted inactivation of coaD in wild type and
      merodiploid backgrounds. It was found that coaD could only be inactivated in the
      presence of an additional gene copy, confirming it to be an essential gene. Using
      a similar approach we found that CoaE was also essential for the survival of M.
      tuberculosis. RT-PCR analysis showed that both coaD and coaE were transcribed in
      M. tuberculosis. Amino acids alignment and phylogenetic analysis showed CoaD to
      be distantly related to the human counterpart while CoaE was found to be
      relatively similar to the human enzyme. Analysis of CoaD and CoaE structures at
      molecular level allowed us to identify unique residues in the Mtb proteins, thus
      providing a selectivity handle. The essentiality and selectivity analysis
      combined with the published biochemical characterization of CoaD and CoaE makes
      them suitable targets for developing inhibitors against M. tuberculosis.

PMID- 22954586
TI  - High-resolution fish on DNA fibers for low-copy repeats genome architecture
      studies.
AB  - Low-copy repeats (LCRs) constitute 5% of the human genome. LCRs act as substrates
      for non-allelic homologous recombination (NAHR) leading to genomic structural
      variation. The aim of this study was to assess the potential of Fiber-FISH for
      LCRs direct visualization to support investigations of genome architecture within
      these challenging genomic regions. We describe a set of Fiber-FISH experiments
      designed for the study of the LCR22-2. This LCR is involved in recurrent
      reorganizations causing different genomic disorders. Four fosmid clones covering
      the entire length of the LCR22-2 and two single-copy BAC-clones, delimiting the
      LCR22-2 proximally and distally, were selected. The probes were hybridized in
      different multiple color combinations on DNA fibers from two karyotypically
      normal cell lines. We were able to identify three distinct structural haplotypes
      characterized by differences in copy-number and arrangement of the LCR22-2 genes
      and pseudogenes. Our results show that Multicolor Fiber-FISH is a viable
      methodological approach for the analysis of genome organization within complex
      LCR regions.

PMID- 22954588
TI  - Impacts of normal aging on different working memory tasks: implications from an
      fMRI study.
AB  - PURPOSE: To evaluate patterns of activation, convergence and divergence of three
      functional magnetic resonance imaging (fMRI) Working Memory (WM) tasks in two
      different age groups. We want to understand potential impact of task and
      subjects' age on WM activations as well as most important areas with regard to WM
      functions. MATERIALS AND METHODS: Thirty-five healthy volunteers completed
      visual, verbal, and novel auditory WM tasks. The subjects were selected from age
      extremes to depict possible impact of normal aging. General Linear Model was used
      to report significant activations and the effect of group. One-to-one comparison
      of the tasks and Combined Task Analysis was also performed. RESULTS: Most of the
      observed differences between the tasks were seen in areas that were responsible
      for feature processing. Frontal regions were mainstay activation areas,
      regardless of the utilized stimulus. We found an age-related reduction in
      activity of visual (in visually-presented tasks) and auditory (in auditory task)
      cortices but an age-related increase in prefrontal cortex for all tasks.
      CONCLUSION: Regardless of the type of the task stimuli, frontal regions are the
      most important activation areas in WM processing. These areas are also main
      targets of age-related changes with regard to activation patterns. Our results
      also indicate that prefrontal overactivity in working memory might be a
      compensatory effort to mask age-related decline in sensory processing.

PMID- 22954587
TI  - Recent progress in the metabolic engineering of alkaloids in plant systems.
AB  - Plant alkaloids have a rich chemical ecology that has been exploited for
      medicinal purposes for thousands of years. Despite being highly represented
      within today's pharmacopoeia, relatively little is known about the biosynthesis,
      regulation and transport of these molecules. Understanding how nature synthesizes
      plant alkaloids will enhance our ability to overproduce--that is, to
      metabolically engineer--these medicinally useful compounds as well as new-to
      nature compounds (with potentially improved bioactivity) derived from these
      natural scaffolds. Recent progress in the metabolic engineering of nitrogen
      containing plant natural products--specifically the monoterpene indole alkaloids,
      the benzylisoquinoline alkaloids and the glucosinolates--was made possible
      through the characterization of various components in both native and engineered
      enzymatic pathways. The subsequent reconfiguration and tuning of these biological
      'parts' has enabled the production of selected products at increasingly higher
      titers.

PMID- 22954589
TI  - Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and
      nongenomic interference with MAPK signaling pathways.
AB  - Glucocorticoids (GCs) are steroid hormones produced by the adrenal gland and
      regulated by the hypothalamus-pituitary-adrenal axis. GCs mediate effects that
      mostly result in transcriptional regulation of glucocorticoid receptor target
      genes. Mitogen-activated protein kinases (MAPKs) comprise a family of signaling
      proteins that convert extracellular stimuli into the activation of intracellular
      transduction pathways via phosphorylation of a cascade of substrates. They
      modulate a variety of physiological cell processes, such as proliferation,
      apoptosis, and development. However, when MAPKs are improperly activated by
      proinflammatory and/or extracellular stress stimuli, they contribute to the
      regulation of proinflammatory transcription factors, thus perpetuating activation
      of the inflammatory cascade. One of the mechanisms by which GCs exert their anti
      inflammatory effects is negative interference with MAPK signaling pathways.
      Several functional interactions between GCs and MAPK signaling have been
      discovered and studied. Some of these interactions involve the GC-mediated up
      regulation of proteins that in turn interfere with the activation of MAPK, such
      as glucocorticoid-induced-leucine zipper, MAPK phosphatase-1, and annexin-1.
      Other mechanisms include activated GR directly interacting with components of the
      MAPK pathway and negatively regulating their activation. The multiple
      interactions between GCs and MAPK pathways and their potential biological
      relevance in mediating the anti-inflammatory effects of GCs are reviewed.

PMID- 22954590
TI  - Loss of Mel-18 enhances breast cancer stem cell activity and tumorigenicity
      through activating Notch signaling mediated by the Wnt/TCF pathway.
AB  - Mel-18 has been proposed as a negative regulator of Bmi-1, a cancer stem cell
      (CSC) marker, but it is still unclear whether Mel-18 is involved in CSC
      regulation. Here, we examined the effect of Mel-18 on the stemness of human
      breast CSCs. In Mel-18 small hairpin RNA (shRNA)-transduced MCF-7 cells, side
      population (SP) cells and breast CSC surface marker (CD44(+)/CD24(-)/ESA(+))
      expressing cells, which imply a CSC population, were enriched. Moreover, the self
      renewal of CSCs was enhanced by Mel-18 knockdown, as measured by the ability for
      tumorsphere formation in vitro and tumor-initiating capacity in vivo. Similarly,
      Mel-18 overexpression inhibited the number and self-renewal activity of breast
      CSCs in SK-BR-3 cells. Furthermore, our data showed that Mel-18 blockade up
      regulated the expression of the Wnt/TCF target Jagged-1, a Notch ligand, and
      consequently activated the Notch pathway. Pharmacologic inhibition of the Notch
      and Wnt pathways abrogated Mel-18 knockdown-mediated tumorsphere formation
      ability. Taken together, our findings suggest that Mel-18 is a novel negative
      regulator of breast CSCs that inhibits the stem cell population and in vitro and
      in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling.

PMID- 22954591
TI  - Neuroendocrine control of female reproductive function by the activin receptor
      ALK7.
AB  - Activins are critical components of the signaling network that controls female
      reproduction. However, their roles in hypothalamus, and the specific functions of
      their different receptors, have not been elucidated. Here, we investigated the
      expression and function of the activin receptor ALK7 in the female reproductive
      axis using Alk7-knockout mice. ALK7 was found in subsets of SF1-expressing
      granulosa cells in the ovary, FSH gonadotrophs in the pituitary, and NPY
      expressing neurons in the arcuate nucleus of the hypothalamus. Alk7-knockout
      females showed delayed onset of puberty and abnormal estrous cyclicity, had
      abnormal diestrous levels of FSH and LH in serum, and their ovaries showed
      premature depletion of follicles, oocyte degeneration, and impaired responses to
      exogenous gonadotropins. In the arcuate nucleus, mutant mice showed reduced
      expression of Npy mRNA and lower numbers of Npy-expressing neurons than wild-type
      controls. Alk7 knockouts showed a selective loss of arcuate NPY/AgRP innervation
      in the medial preoptic area, a key central regulator of reproduction. These
      results indicate that ALK7 is an important regulator of female reproductive
      function and reveal a new role for activin signaling in the control of
      hypothalamic gene expression and wiring. Alk7 gene variants may contribute to
      female reproductive disorders in humans, such as polycystic ovary syndrome.

PMID- 22954592
TI  - Modified abdominoplasty incision for short scar.

PMID- 22954593
TI  - Nasolabial fold augmentation with SMAS graft.
AB  - This case report shows a new technique for inserting superficial
      musculoaponeurotic system (SMAS) tissue as autologous filling of deep nasolabial
      folds during an SMAS or minimal access cranial suspension (MACS) facelift
      procedure with satisfying aesthetic results. The technique avoids visible scars
      on the cheek and does not require insertion through a potential contaminated area
      such as nasal mucosa.

PMID- 22954594
TI  - The serotonin transporter gene and functional and pathological adaptation to
      environmental variation across the life span.
AB  - In analogy with the accepted view that behaviour is shaped by gene*environment
      (G*E) interactions, G*E studies are exponentially increasing in the field of
      psychiatry. Whereas research was primarily driven by the premature view that
      negative environmental stimuli can trigger psychopathology in those subjects that
      are genetically predisposed, a closer look at the available data shows that G*E
      interactions are much more complex than initially thought. Here, we discuss G*E
      studies focussing on serotonin transporter (5-HTT, SERT, SLC6A4) gene variation
      in humans, monkeys, and rodents. Recent studies, across species, confirm the
      theorized 'for-better-and-for-worse' effect of low activity serotonin transporter
      genotypes. In addition, while 5-HTT*E interactions were thought to take place in
      early life, recent evidence illustrates that these interactions are also
      manifested in adulthood. Therefore, we discuss data based on 5-HTT*E
      interactions, and propose a model in which predictive adaptive responses (PARs),
      as shaped by early life 5-HTT*E interactions, shape responses to environmental
      challenges in later life, i.e. reflecting 5-HTT*E*E interactions.

PMID- 22954595
TI  - Comparative vesicle proteomics reveals selective regulation of protein expression
      in chestnut blight fungus by a hypovirus.
AB  - The chestnut blight fungus (Cryphonectria parasitica) and hypovirus constitute a
      model system to study fungal pathogenesis and mycovirus-host interaction.
      Knowledge in this field has been gained largely from investigations at gene
      transcription level so far. Here we report a systematic analysis of the vesicle
      proteins of the host fungus with/without hypovirus infection. Thirty-three
      differentially expressed protein spots were identified in the purified vesicle
      protein samples by two-dimensional electrophoresis and mass spectrometry. Down
      regulated proteins were mostly cargo proteins involved in primary metabolism and
      energy generation and up-regulated proteins were mostly vesicle associated
      proteins and ABC transporter. A virus-encoded protein p48 was found to have four
      forms with different molecular mass in vesicles from the virus-infected strain.
      While a few of the randomly selected differentially expressed proteins were in
      accordance with their transcription profiles, majority were not in agreement with
      their mRNA accumulation patterns, suggesting that an extensive post
      transcriptional regulation may have occurred in the host fungus upon a hypovirus
      infection.

PMID- 22954597
TI  - Phosphate starvation and membrane lipid remodeling in seed plants.
AB  - Phosphate is an essential, yet scarce, nutrient that seed plants need to maintain
      viability. Phosphate-starved plants utilize their membrane phospholipids as a
      major source for internal phosphate supply by replacing phospholipids in their
      membranes with the non-phosphorus galactolipid, digalactosyldiacylglycerol. This
      membrane lipid remodeling has drawn much attention as a model of metabolic
      switching from phospholipids to the galactolipid. In the past decade, a
      considerable effort has been devoted to unraveling the molecular biology of this
      phenomenon. This review thus aims to summarize recent achievements with a focus
      on metabolic pathways during lipid remodeling.

PMID- 22954596
TI  - A label-free proteome analysis strategy for identifying quantitative changes in
      erythrocyte membranes induced by red cell disorders.
AB  - Red blood cells have been extensively studied but many questions regarding
      membrane properties and pathophysiology remain unanswered. Proteome analysis of
      red cell membranes is complicated by a very wide dynamic range of protein
      concentrations as well as the presence of proteins that are very large, very
      hydrophobic, or heterogeneously glycosylated. This study investigated the removal
      of other blood cell types, red cell membrane extraction, differing degrees of
      fractionation using 1-D SDS gels, and label-free quantitative methods to
      determine optimized conditions for proteomic comparisons of clinical blood
      samples. The results showed that fractionation of red cell membranes on 1-D SDS
      gels was more efficient than low-ionic-strength extractions followed by 1-D gel
      fractionation. When gel lanes were sliced into 30 uniform slices, a good depth of
      analysis that included the identification of most well-characterized, low
      abundance red cell membrane proteins including those present at 500 to 10,000
      copies per cell was obtained. Furthermore, the size separation enabled detection
      of changes due to proteolysis or in vivo protein crosslinking. A combination of
      Rosetta Elucidator quantitation and subsequent statistical analysis enabled the
      robust detection of protein differences that could be used to address unresolved
      questions in red cell disorders. This article is part of a Special Issue
      entitled: Integrated omics.

PMID- 22954598
TI  - Oxidation of ammonia to nitrogen over Pt/Fe/ZSM5 catalyst: influence of catalyst
      support on the low temperature activity.
AB  - In this study, Pt/Fe/ZSM5 catalysts were applied to oxidation of ammonia, where
      the catalysts showed good low-temperature activity (<= 200 degrees C) for
      converting ammonia into nitrogen. With 1.5% Pt/0.5% Fe/ZSM5 catalyst, we could
      obtain 81% NH(3) conversion and 93% N(2) selectivity at 175 degrees C at the
      short contact-time of w/f=0.00012 g min/mL. Through the characterization studies
      using high-resolution transmission electron microscopy (HRTEM) and X-ray
      spectroscopies (XRD, XPS), we could find that the active species was
      collaborating Pt/Fe species, which structure and activity were largely influenced
      by support material - in a positive way by ZSM5, rather than by Al(2)O(3) and
      SiO(2). When using ZSM5 as the support material, Pt was highly dispersed
      exclusively on the Fe oxide, and the valence state and dispersion of Pt changed
      according to Fe loading amount.

PMID- 22954599
TI  - Facilitating role of biogenetic schwertmannite in the reduction of Cr(VI) by
      sulfide and its mechanism.
AB  - The efficient conversion of Cr(VI) to Cr(III) has attracted an increasing concern
      in recent years owing to its threat to the environment. In the present paper, the
      catalytic role of biogenetic schwertmannite in the reduction of Cr(VI) by sulfide
      and its mechanism were investigated under different conditions through batch
      experiments. The results demonstrated that schwertmannite markedly accelerated
      the removal of Cr(VI) by sulfide, and the rates of the reaction were enhanced by
      11, 8 and 6 times, respectively at pH 7.5, 8.0 and 8.8 as compared with control
      (no schwertmannite). In addition, the conversion of Cr(VI) into Cr(III) increased
      with schwertmannite loading and temperature. However, the facilitating role of
      schwertmannite in the reduction of Cr(VI) by sulfide was markedly suppressed by
      an introduction of F(-), a complex agent for Fe(III). It is concluded that the
      catalysis of schwertmannite results from the activated Fe(III) on the surface of
      schwertmannite, serving as a "bridge" in the transportation of electrons between
      sulfide and Cr(VI), and leading to the improving reduction of Cr(VI) by sulfide.

PMID- 22954600
TI  - Mutual effects of copper and phosphate on their interaction with gamma-Al2O3:
      combined batch macroscopic experiments with DFT calculations.
AB  - The mutual effects of Cu(II) and phosphate on their interaction with gamma
      Al(2)O(3) are investigated by using batch experiments combined with density
      functional theory (DFT) calculations. The results of batch experiments show that
      coexisting phosphate promotes the retention of Cu(II) on gamma-Al(2)O(3), whereas
      phosphate retention is not affected by coexisting Cu(II) at low initial phosphate
      concentrations (<= 3.6 mg P/L). Cu-phosphate aqueous complexes control Cu(II)
      retention through the formation of type B ternary surface complexes (where
      phosphate bridges gamma-Al(2)O(3) and Cu(II)) at pH 5.5. This deduction is
      further supported by the results of DFT calculations. More specifically, the DFT
      calculation results indicate that the type B ternary surface complexes prefer to
      form outer-sphere or monodentate inner-sphere binding mode under our experimental
      conditions. The enhancement of phosphate retention on gamma-Al(2)O(3) in the
      presence of Cu(II) at high initial phosphate concentrations (>3.6 mg P/L) may be
      attributed to the formation of 1:2 Cu(II)-phosphate species and/or surface
      precipitates. Understanding the mutual effects of phosphate and Cu(II) on their
      mobility and transport in mineral/water environments is more realistic to design
      effective remediation strategies for reducing their negative impacts on
      aquatic/terrestrial environments.

PMID- 22954601
TI  - Arsenic mineral dissolution and possible mobilization in mineral-microbe
      groundwater environment.
AB  - Arsenic (As) is widely distributed in the nature as ores or minerals. It has been
      attracted much attention for the global public health issue, especially for
      groundwater As contamination. The aim of this study was to elucidate the
      characteristics of microbes in groundwater where As-minerals were dissolved. An
      ex situ experiment was conducted with 7 standard As-minerals in bacteria-free
      groundwater and stored in experimental vessels for 1 year without supplementary
      nutrients. The pH (6.7-8.4) and EhS.H.E. (24-548 mV) changed between initial (0
      day) and final stages (365 days) of experiment. The dissolution of As was
      detected higher from arsenolite (4240 +/- 8.69 mg/L) and native arsenic (4538 +/-
      9.02 mg/L), whereas moderately dissolved from orpiment (653 +/- 3.56 mg/L) and
      realgar (319 +/- 2.56 mg/L) in compare to arsenopyrite (85 +/- 1.25mg/L) and
      tennantite (3 +/- 0.06 mg/L). Optical microscopic, scanning electron microscopic
      observations and flurometric enumeration revealed the abundance of As-resistant
      bacillus, coccus and filamentous types of microorganisms on the surface of most
      of As-mineral. 4'-6-Diamidino-2-phenylindole (DAPI)-stained epifluorescence
      micrograph confirmed the presence of DNA and carboxyfluorescein diacetate (CFDA)
      staining method revealed the enzymatically active bacteria on the surface of As
      minerals such as in realgar (As4S4). Therefore, the microbes enable to survive
      and mobilize the As in groundwater by dissolution/bioweathering of As-minerals.

PMID- 22954602
TI  - Low concentrations of polycyclic aromatic hydrocarbons promote the growth of
      Microcystis aeruginosa.
AB  - There is an increasing need to describe the growth characteristics of
      cyanobacteria exposed to polycyclic aromatic hydrocarbons (PAHs) because the
      presence of PAHs in lakes is known to affect the growth of this kind of
      microorganisms. In this work, the effects of low concentrations of PAHs on
      Microcystis aeruginosa (M. aeruginosa) were investigated. M. aeruginosa were
      cultivated in the medium with a mixture of PAHs (0.486 mg L(-1) naphthalene,
      0.049 mg L(-1) phenanthrene, and 0.0015 mg L(-1) pyrene) and different
      concentrations of nitrogen and phosphorus. During 31 d of incubation, profiles of
      cell number and chlorophyll-a content were determined. The results indicated that
      when the concentration of an individual PAH was below its no observed effect
      concentration (NOEC), the exposure of M. aeruginosa to a mixture of PAHs markedly
      promoted cell density after 7d of culture. Low concentrations of nutrients in the
      medium improved the growth of M. aeruginosa in the presence of PAHs. When
      concentrations of both phosphorus and nitrogen were 50% lower than those of the
      control, the specific growth rate of M. aeruginosa increased by 100% when exposed
      to PAHs, and the generation time decreased from 10.5 to 5.3d. The chlorophyll-a
      content in medium also increased from 2.23 to 3.18 MUg mL(-1), which was
      attributed to an increase in cell numbers.

PMID- 22954603
TI  - Automatic dosage of hydrogen peroxide in solar photo-Fenton plants: development
      of a control strategy for efficiency enhancement.
AB  - The solar photo-Fenton process is widely used for the elimination of pollutants
      in aqueous effluent and, as such, is amply cited in the literature. In this
      process, hydrogen peroxide represents the highest operational cost. Up until now,
      manual dosing of H(2)O(2) has led to low process performance. Consequently, there
      is a need to automate the hydrogen peroxide dosage for use in industrial
      applications. As it has been demonstrated that a relationship exists between
      dissolved oxygen (DO) concentration and hydrogen peroxide consumption, DO can be
      used as a variable in optimising the hydrogen peroxide dosage. For this purpose,
      a model was experimentally obtained linking the dynamic behaviour of DO to
      hydrogen peroxide consumption. Following this, a control system was developed
      based on this model. This control system - a proportional and integral controller
      (PI) with an anti-windup mechanism - has been tested experimentally. The assays
      were carried out in a pilot plant under sunlight conditions and with paracetamol
      used as the model pollutant. In comparison with non-assisted addition methods (a
      sole initial or continuous addition), a decrease of 50% in hydrogen peroxide
      consumption was achieved when the automatic controller was used, driving an
      economic saving and an improvement in process efficiency.

PMID- 22954604
TI  - Pulse current enhanced electrodialytic soil remediation--comparison of different
      pulse frequencies.
AB  - Energy consumption is an important factor influencing the cost of electrodialytic
      soil remediation (EDR). It has been indicated that the pulse current (in low
      frequency range) could decrease the energy consumption during EDR. This work is
      focused on the comparison of energy saving effect at different pulse frequencies.
      Based on the restoration of equilibrium, the relaxation process of the soil-water
      system was investigated by chronopotentiometric analysis to find the optimal
      relaxation time for energy saving. Results showed that the pulse current
      decreased the energy consumption with different extent depending on the pulse
      frequency. The experiment with the frequency of 16 cycles per day showed the best
      restoration of equilibrium and lowest energy consumption. The energy consumption
      per removed heavy metals was lower in pulse current experiments than constant
      current and increased with the pulse frequency. It was found that the
      transportation of cations through the cation exchange membrane was the rate
      controlling step both in constant and pulse current experiments, thus responsible
      for the major energy consumption. Substitution of the cation exchange membrane
      with filter paper resulted in a dramatic decrease in energy consumption, but this
      change impeded the acidification process and thus the removal of heavy metals
      decreased significantly.

PMID- 22954605
TI  - Mechanical properties and microstructure analysis of fly ash geopolymeric
      recycled concrete.
AB  - Six mixtures with different recycled aggregate (RA) replacement ratios of 0%, 50%
      and 100% were designed to manufacture recycled aggregate concrete (RAC) and
      alkali-activated fly ash geopolymeric recycled concrete (GRC). The physical and
      mechanical properties were investigated indicating different performances from
      each other. Optical microscopy under transmitted light and scanning electron
      microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX) were
      carried out in this study in order to identify the mechanism underlying the
      effects of the geopolymer and RA on concrete properties. The features of
      aggregates, paste and interfacial transition zone (ITZ) were compared and
      discussed. Experimental results indicate that using alkali-activated fly ash
      geopolymer as replacement of ordinary Portland cement (OPC) effectively improved
      the compressive strength. With increasing of RA contents in both RAC and GRC, the
      compressive strength decreased gradually. The microstructure analysis shows that,
      on one hand, the presence of RA weakens the strength of the aggregates and the
      structure of ITZs; on the other hand, due to the alkali-activated fly ash in
      geopolymer concrete, the contents of Portlandite (Ca(OH)(2)) and voids were
      reduced, as well as improved the matrix homogeneity. The microstructure of GRC
      was changed by different reaction products, such as aluminosilicate gel.

PMID- 22954606
TI  - Investigation on reusing water treatment residuals to remedy soil contaminated
      with multiple metals in Baiyin, China.
AB  - In this work, the remediation of soils contaminated with multiple metals using
      ferric and alum water treatment residuals (FARs) in Baiyin, China, was
      investigated. The results of metals fractionation indicated that after the soil
      was treated with FARs, arsenic (As), lead (Pb), nickel (Ni), zinc (Zn) and copper
      (Cu) could be transformed into more stable forms, i.e., As bound in crystalline
      Fe/Al oxides and other metals in the oxidable and residual forms. However, the
      forms of chromium (Cr) and cadmium (Cd) were unaffected. Interestingly, due to
      the effect of FARs, barium (Ba) was predominantly transformed into more mobile
      forms. The bioaccessibility extraction test demonstrated that the FARs reduced
      the bioaccessibility of As by 25%, followed by Cu, Cr, Zn, Ni and Pb. The
      bioaccessibility of Cd and Ba were increased; in particular, there was an
      increase of 41% for Ba at the end of the test. In conclusion, the FARs can be
      used to remedy soil contaminated with multiple metals, but comprehensive studies
      are needed before practical applications of this work.

PMID- 22954607
TI  - S-allyl derivatives of 6-mercaptopurine are highly potent drugs against human B
      CLL through synergism between 6-mercaptopurine and allicin.
AB  - S-allylthio-6-mercaptopurine and its ribose derivative were tested for anti
      leukemic activity, using a human- mouse B-CLL model. The novel prodrugs contain
      two components, a purine analog, which interferes with DNA synthesis, and an S
      allylthio, readily engaging in thiol-disulfide exchange reactions. The latter
      component targets the redox homeostasis which is more sensitive in leukemic
      cells, than in normal B-cells. Upon administration, the prodrug permeates cells,
      instantly reacts with free thiol, forming S-allyl mixed disulfides and releasing
      purine. Several cycles of thiol-disulfide exchange reactions occur, thus
      extending the duration of the prodrug effects. The concerted action of 2
      components, as compared with purine alone, boosted in vitro apoptotis in B-CLL
      cells from 10% to 38%, and decreased in vivo engraftment of B-CLL from 30% to
      0.7%.

PMID- 22954608
TI  - Thrombocytopenia at diagnosis as an important negative prognostic marker in
      isolated 5q- MDS (IPSS low and intermediate-1).

PMID- 22954609
TI  - Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute
      myeloid leukemia (AML)/myelodysplastic syndrome (MDS): how can we improve
      outcomes in the near future?
AB  - Substantive advances in the past decade or so have allowed for a wider spectrum
      of patients to undergo allo-HSCT and have increased its safety, thus broadening
      the application of this therapy[36]. That said, disease persistence or (more
      commonly) recurrence remains as primary problems. A combination of "extrinsic"
      and "intrinsic" methods is now available and ready for additional clinical
      testing and/or utilization. Fortunately, one can be somewhat optimistic that
      better results will be achieved, perhaps very soon. However, and as these
      strategies and techniques are evaluated, it should be realized that some may be
      too complex and/or expensive for widespread use as the need to reduce costs
      becomes more pressing.

PMID- 22954610
TI  - Aging, inflammation, and HIV infection.
AB  - Prolonged survival in HIV infection is accompanied by an increased frequency of
      non-HIV-related comorbidities. A number of age-related comorbidities occur
      earlier in HIV-infected patients than in individuals without HIV infection. This
      "accelerated aging" appears to be largely related to chronic inflammation,
      chronic immune activation, and immunosenescence in HIV infection. Levels of
      markers of inflammation and coagulopathy are elevated in HIV-infected patients,
      and elevations in markers such as high-sensitivity C-reactive protein, D-dimer,
      and interleukin 6 (IL-6) have been associated with increased risk for
      cardiovascular disease, opportunistic conditions, or all-cause mortality. In both
      HIV infection and aging, immunosenescence is marked by an increased proportion of
      CD28-, CD57+ memory CD8+ T cells with reduced capacity to produce interleukin 2
      (IL-2), increased production of IL-6, resistance to apoptosis, and shortened
      telomeres. A number of AIDS Clinical Trials Group studies are under way to
      examine treatment aimed at reducing chronic inflammation and immune activation in
      HIV infection. This article summarizes a presentation by Judith A. Aberg, MD, at
      the IAS-USA live continuing medical education course held in New York City in
      October 2011.

PMID- 22954611
TI  - The kidney in HIV infection: beyond HIV-associated nephropathy.
AB  - Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in HIV
      infected persons than in the general population. AKI is associated with poor
      health outcomes, including increased risk of heart failure, cardiovascular
      events, end-stage renal disease (ESRD), and mortality. The most common causes of
      AKI in HIV-infected persons are systemic infections and adverse drug effects. The
      prevalence of CKD is rising in the HIV-infected population and CKD is
      increasingly likely to be caused by comorbid conditions, such as diabetes and
      hypertension, that frequently cause CKD in the general population. Guidelines for
      CKD screening in HIV-infected patients are being revised. It is currently
      recommended that all patients be screened for creatinine-based estimates of
      glomerular filtration rate and for urine protein at the time of HIV diagnosis.
      Annual screening is recommended for high-risk patients. Hemodialysis, peritoneal
      dialysis, and kidney transplantation are all options for treating ESRD in HIV
      infected patients. Hemodialysis and peritoneal dialysis offer similar survival in
      HIV-infected patients with ESRD. In selected patients with well-controlled HIV
      infection, kidney transplantation is associated with survival intermediate
      between that in the overall transplant population and that among transplant
      recipients older than 65 years. This article summarizes a presentation by
      Christina M. Wyatt, MD, at the IAS-USA continuing medical education program held
      in Chicago in May 2012, describing AKI and CKD using case illustrations.

PMID- 22954612
TI  - Travel medicine and vaccines for HIV-infected travelers.
AB  - For the purposes of vaccination, persons with asymptomatic HIV infection and CD4+
      cell counts of 200/MUL to 500/MUL are considered to have limited immune deficits
      and are generally candidates for immunization. HIVinfected persons with CD4+ cell
      counts less than 200/MUL or history of an AIDS-defining illness should not
      receive live-attenuated viral or bacterial vaccines because of the risk of
      serious systemic disease and suboptimal response to vaccination. Available data
      indicate that immunization during antiretroviral therapy restores vaccine
      immunogenicity, improves the rate and persistence of immune responses, and
      reduces risk of vaccine-related adverse events, although vaccine responses often
      are suboptimal. Major issues for travelers to the developing world are vaccine
      preventable illnesses (hepatitis A virus, yellow fever, and typhoid fever),
      traveler's diarrhea, and malaria. This article summarizes a presentation by D.
      Scott Smith, MD, at the IAS-USA continuing medical education program held in San
      Francisco in April 2012.

PMID- 22954613
TI  - FDG-PET imaging in the diagnosis of HIV-associated multicentric Castleman
      disease: something is still missing.
AB  - Now that [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) has
      become an established imaging tool in oncology, it is attracting interest in the
      field of infectious diseases. Several studies have used FDG-PET to examine the
      pathophysiology of HIV infection as well as other conditions such as
      lipodystrophic syndrome and HIV-related neurocognitive disorders. In clinical
      practice, FDG-PET has been proposed to assess fever of unknown origin or with
      lymphoproliferative disorders such as Castleman disease in individuals with HIV
      infection.

PMID- 22954614
TI  - Applications of optically detected MRI for enhanced contrast and penetration in
      metal.
AB  - We report quantitative measurements using optically detected magnetic resonance
      imaging (MRI) for enhanced pH contrast and flow inside porous metals. Using a
      gadolinium chelate as the pH contrast agent, we show the response is 0.6s(-1) mM(
      1) per pH unit at the ambient magnetic field for the pH range 6-8.5. A stopped
      flow scheme was used to directly measure T(1) relaxation time to determine the
      relaxivity. Flow profiles and images were obtained for a series of porous metals
      with different average pore sizes. The signal amplitudes and spatial
      distributions were compared. A clogged region in one of the samples was revealed
      using optically detected MRI but not optical imaging or scanning electron
      microscopy. These applications will significantly broaden the impact of optically
      detected MRI in chemical imaging and materials research.

PMID- 22954615
TI  - Incidence, mass and variety of plastics ingested by Laysan (Phoebastria
      immutabilis) and Black-footed Albatrosses (P. nigripes) recovered as by-catch in
      the North Pacific Ocean.
AB  - Laysan Albatrosses (Phoebastria immutabilis) and Black-footed Albatrosses (P.
      nigripes) ingest plastic debris, as evidenced by studies showing plastic in the
      digestive contents of their chicks, but there is little documentation of the
      frequency and amount of ingested plastics carried in foraging adults. In this
      study, we quantify plastics among the digestive contents of 18 Laysan Albatrosses
      and 29 Black-footed Albatrosses collected as by-catch in the North Pacific Ocean.
      We found ingested plastic in 30 of the 47 birds examined, with Laysan Albatrosses
      exhibiting a greater frequency of plastic ingestion (83.3% n=18) than Black
      footed Albatrosses (51.7% n=29) (X(2)=4.8, df=1, P=0.03). Though the mass of
      ingested plastic in both species (mean+/-SD=0.463g+/-1.447) was lower than
      previously noted among albatross chicks, the high frequency of ingested plastic
      we found in this study suggests that long-term effects, e.g. absorption of
      contaminants from plastics, may be of concern throughout the population.

PMID- 22954616
TI  - Examination of Org 26576, an AMPA receptor positive allosteric modulator, in
      patients diagnosed with major depressive disorder: an exploratory, randomized,
      double-blind, placebo-controlled trial.
AB  - Org 26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance
      glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to
      explore safety, tolerability, pharmacokinetics, and pharmacodynamics of Org 26576
      in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD)
      and optimal titration schedule in a multiple rising dose paradigm (range 100 mg
      BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID,
      400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based
      on the number of moderate intensity adverse events reported at the 600 mg BID
      dose level, the MTD established in Part I was 450 mg BID. Symptomatic improvement
      as measured by the Montgomery-Asberg Depression Rating Scale was numerically
      greater in the Org 26576 groups than in the placebo group in both study parts. In
      Part II, the 400 mg BID dose was associated with improvements in executive
      functioning and speed of processing cognitive tests. Org 26576 was also
      associated with growth hormone increases and cortisol decreases at the end of
      treatment but did not influence prolactin or brain-derived neurotrophic factor.
      The quantitative electroencephalogram index Antidepressant Treatment Response at
      Week 1 was able to significantly predict symptomatic response at endpoint in the
      active treatment group, as was early improvement in social acuity. Overall, Org
      26576 demonstrated good tolerability and pharmacokinetic properties in depressed
      patients, and pharmacodynamic endpoints suggested that it may show promise in
      future well-controlled, adequately powered proof of concept trials.

PMID- 22954618
TI  - [Constrictive pericarditis - new methods in the diagnosis of an old disease: a
      case report].
AB  - Constrictive pericarditis is a rare clinical entity that can pose diagnostic
      problems. The gold standard for diagnosis is cardiac catheterization with
      analysis of intracavitary pressure curves, which are high and, in end-diastole,
      equal in all chambers. The diastolic profile in both ventricles presents the
      classic dip-and-plateau pattern and the difference between the diastolic
      pressures of both ventricles should not exceed 3-5mmHg. Unfortunately, these
      traditional criteria are not always present and in fact the sensitivity and
      specificity of equalization of diastolic pressures are relatively low and of
      limited value in individual patients. This highlights the need to use new cardiac
      imaging techniques to resolve any doubts. The case described here is a good
      example.

PMID- 22954617
TI  - A new microRNA target prediction tool identifies a novel interaction of a
      putative miRNA with CCND2.
AB  - Computational methods for miRNA target prediction vary in the algorithm used; and
      while one can state opinions about the strengths or weaknesses of each particular
      algorithm, the fact of the matter is that they fall substantially short of
      capturing the full detail of physical, temporal and spatial requirements of
      miRNA::target-mRNA interactions. Here, we introduce a novel miRNA target
      prediction tool called Targetprofiler that utilizes a probabilistic learning
      algorithm in the form of a hidden Markov model trained on experimentally verified
      miRNA targets. Using a large scale protein downregulation data set we validate
      our method and compare its performance to existing tools. We find that
      Targetprofiler exhibits greater correlation between computational predictions and
      protein downregulation and predicts experimentally verified miRNA targets more
      accurately than three other tools. Concurrently, we use primer extension to
      identify the mature sequence of a novel miRNA gene recently identified within a
      cancer associated genomic region and use Targetprofiler to predict its potential
      targets. Experimental verification of the ability of this small RNA molecule to
      regulate the expression of CCND2, a gene with documented oncogenic activity,
      confirms its functional role as a miRNA. These findings highlight the competitive
      advantage of our tool and its efficacy in extracting biologically significant
      results.

PMID- 22954619
TI  - [Linear accelerator radiosurgery for brainstem arteriovenous malformations. Long
      term results].
AB  - OBJECTIVE: Arteriovenous malformations (AVM) in the brainstem carry a high risk
      of recurrent haemorrhage, mortality and morbidity. Treatment options are limited
      and mainly based on stereotactic radiosurgery. We studied the results of our
      series of brainstem AVM treated with linear accelerator (LINAC) and with a long
      term follow-up. METHODS: We retrospectively analysed the clinical and
      radiological data of 41 consecutive patients with brainstem AVM treated by
      radiosurgery with a 6MV linear accelerator between 1992 and 2010. Twenty five
      lesions were located in the mesencephalon, 14 in the pons, one in the medulla
      oblongata and one was bulbopontine. We analysed the treatment results in relation
      to survival, rate of radiological obliteration, rebleeding, and treatment
      toxicity. RESULTS: The obliteration rate confirmed by angiography/MRA was 59.5%
      on 38 controlled patients. The mean follow-up period was 61 months (range: 6.7
      178) and the margin dose was 14Gy in most treatments. Up to 39% of patients
      received more than one radiosurgery procedure to achieve closure of the
      malformation. No statistical correlation was found with the margin dose, presence
      of pretreatment haemorrhage, nidus diameter or score on the Pollock-Flickinger
      grading system. The annual haemorrhage rate after radiosurgery was 3.2%. Three
      patients died from rebleeding and actuarial survival rate was 88% at 5 and 10
      years after treatment. Four patients suffered new transient neurological deficits
      due to toxicity, and only one presented a permanent deficit (2.6%). CONCLUSIONS:
      Nidus obliteration in brainstem AVM must be achieved according to three main
      criteria: maximum obliteration rate forced by the high rate of rebleeding,
      minimal morbidity given its critical location, and the greatest possible
      accuracy. Stereotactic radiosurgery with our moderate-dose protocol, which we
      believe achieved these three premises, may become an elective therapeutic
      modality for these patients.

PMID- 22954620
TI  - Vision-based motion detection, analysis and recognition of epileptic seizures--a
      systematic review.
AB  - The analysis of human motion from video has been the object of interest for many
      application areas, these including surveillance, control, biomedical analysis,
      video annotation etc. This paper addresses the advances within this topic in
      relation to epilepsy, a domain where human motion is with no doubt one of the
      most important elements of a patient's clinical image. It describes recent
      achievements in vision-based detection, analysis and recognition of human motion
      in epilepsy for marker-based and marker-free systems. An overview of motion
      characterizing features extracted so far is presented separately. The objective
      is to gain existing knowledge in this field and set the route marks for the
      future development of an integrated decision support system for epilepsy
      diagnosis and disease management based on automated video analysis. This review
      revealed that the quantification of motion patterns of selected epileptic
      seizures has been studied thoroughly while the recognition of seizures is
      currently in its beginnings, but however feasible. Moreover, only a limited set
      of seizure types have been analyzed so far, indicating that a holistic approach
      addressing all epileptic syndromes is still missing.

PMID- 22954621
TI  - Comparative study of ligand binding during the postsynthetic stabilization of
      metal oxide nanoparticles.
AB  - In the absence of stabilizers in the reaction medium, the nonaqueous synthesis of
      metal oxide nanoparticles usually results in agglomerated products. Stabilization
      is however often possible in a postsynthetic treatment, involving the addition of
      organic ligands that coordinate to the nanoparticle surface. The ligands are
      commonly expected to chemisorb via functional groups; however, we have recently
      shown that also weakly and unspecifically interacting ligands can lead to
      stabilization. Here, we present detailed investigations on the stabilization,
      comparing the binding of weakly coordinating ligands to a system with strongly
      and selectively binding stabilizers and additionally exploring the effect of
      ligand chain length. Although in all cases stabilization and disintegration of
      agglomerates to the primary particle level are achieved, strong differences are
      observed with respect to the processes at the particle surface. Moreover, these
      processes are shown to be more complex than simple ligand adsorption and need to
      be understood for proper design and choice of stabilizers.

PMID- 22954622
TI  - Utilization of fluorescent probes for the quantification and identification of
      subcellular proteomes and biological processes regulated by lipid peroxidation
      products.
AB  - Oxidative modifications to cellular proteins are critical in mediating redox
      sensitive processes such as autophagy, the antioxidant response, and apoptosis.
      The proteins that become modified by reactive species are often compartmentalized
      to specific organelles or regions of the cell. Here, we detail protocols for
      identifying the subcellular protein targets of lipid oxidation and for linking
      protein modifications with biological responses such as autophagy. Fluorophores
      such as BODIPY-labeled arachidonic acid or BODIPY-conjugated electrophiles can be
      paired with organelle-specific probes to identify specific biological processes
      and signaling pathways activated in response to oxidative stress. In particular,
      we demonstrate "negative" and "positive" labeling methods using BODIPY-tagged
      reagents for examining oxidative modifications to protein nucleophiles. The
      protocol describes the use of these probes in slot immunoblotting, quantitative
      Western blotting, in-gel fluorescence, and confocal microscopy techniques. In
      particular, the use of the BODIPY fluorophore with organelle- or biological
      process-specific dyes and chromophores is highlighted. These methods can be used
      in multiple cell types as well as isolated organelles to interrogate the role of
      oxidative modifications in regulating biological responses to oxidative stress.

PMID- 22954623
TI  - Acute stress responses in salivary alpha-amylase predict increases of plasma
      norepinephrine.
AB  - Current biobehavioral research increasingly employs salivary alpha-amylase (sAA)
      as a surrogate marker for sympathetic nervous system (SNS) activity. While
      different lines of evidence point to the validity of this assumption, the
      literature is inconsistent with regard to associations of sAA with well
      established SNS indicators, such as plasma norepinephrine (NE) or epinephrine
      (E). Small samples as well as application of different stress paradigms might be
      responsible. This study therefore set out to examine the relation between stress
      induced sAA activity with NE and E by exposing a larger and less constrained
      sample to an effective stress protocol. Sixty-six healthy participants (mean age
      24.30+/-4.24 yrs), including n=40 women, n=26 men, n=18 oral contraceptive (OC)
      users, and n=15 habitual smokers, were recruited and subjected to the Trier
      Social Stress Test (TSST). Saliva and blood samples were taken at four time
      points throughout the experiment for later analysis of sAA activity and NE/E
      concentration, respectively. As expected, sAA, NE, and E showed significant
      increases in response to the acute stress induction (all p<0.001). Regression
      analyses (controlling for age, BMI, sex, smoking and OC) revealed that stress
      responses in sAA significantly predicted stress responses in NE (r=0.326;
      p=0.025). Interestingly, stress responses in E predicted NE to a lesser extend
      (beta=0.265; p=0.064). E responses showed no association with sAA (beta=0.265;
      p=0.064). Higher sAA levels were found in habitual smokers (F=4.27; p=0.043) and
      in individuals with lower BMI (F=2.81; p=0.099). In conclusion, current data
      clearly show an association between stress responses of sAA and plasma NE. This
      relationship is stronger than the association of norepinephrine and epinephrine
      responses, thus placing the predictive power of sAA well within the expected
      range for different SNS markers.

PMID- 22954624
TI  - A linear programming model for protein inference problem in shotgun proteomics.
AB  - MOTIVATION: Assembling peptides identified from tandem mass spectra into a list
      of proteins, referred to as protein inference, is an important issue in shotgun
      proteomics. The objective of protein inference is to find a subset of proteins
      that are truly present in the sample. Although many methods have been proposed
      for protein inference, several issues such as peptide degeneracy still remain
      unsolved. RESULTS: In this article, we present a linear programming model for
      protein inference. In this model, we use a transformation of the joint
      probability that each peptide/protein pair is present in the sample as the
      variable. Then, both the peptide probability and protein probability can be
      expressed as a formula in terms of the linear combination of these variables.
      Based on this simple fact, the protein inference problem is formulated as an
      optimization problem: minimize the number of proteins with non-zero probabilities
      under the constraint that the difference between the calculated peptide
      probability and the peptide probability generated from peptide identification
      algorithms should be less than some threshold. This model addresses the peptide
      degeneracy issue by forcing some joint probability variables involving degenerate
      peptides to be zero in a rigorous manner. The corresponding inference algorithm
      is named as ProteinLP. We test the performance of ProteinLP on six datasets.
      Experimental results show that our method is competitive with the state-of-the
      art protein inference algorithms. AVAILABILITY: The source code of our algorithm
      is available at: https://sourceforge.net/projects/prolp/. CONTACT:
      zyhe@dlut.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics Online.

PMID- 22954625
TI  - Performance reproducibility index for classification.
AB  - MOTIVATION: A common practice in biomarker discovery is to decide whether a large
      laboratory experiment should be carried out based on the results of a preliminary
      study on a small set of specimens. Consideration of the efficacy of this approach
      motivates the introduction of a probabilistic measure, for whether a classifier
      showing promising results in a small-sample preliminary study will perform
      similarly on a large independent sample. Given the error estimate from the
      preliminary study, if the probability of reproducible error is low, then there is
      really no purpose in substantially allocating more resources to a large follow-on
      study. Indeed, if the probability of the preliminary study providing likely
      reproducible results is small, then why even perform the preliminary study?
      RESULTS: This article introduces a reproducibility index for classification,
      measuring the probability that a sufficiently small error estimate on a small
      sample will motivate a large follow-on study. We provide a simulation study based
      on synthetic distribution models that possess known intrinsic classification
      difficulties and emulate real-world scenarios. We also set up similar simulations
      on four real datasets to show the consistency of results. The reproducibility
      indices for different distributional models, real datasets and classification
      schemes are empirically calculated. The effects of reporting and multiple-rule
      biases on the reproducibility index are also analyzed. AVAILABILITY: We have
      implemented in C code the synthetic data distribution model, classification
      rules, feature selection routine and error estimation methods. The source code is
      available at http://gsp.tamu.edu/Publications/supplementary/yousefi12a/.

PMID- 22954626
TI  - HighSSR: high-throughput SSR characterization and locus development from next-gen
      sequencing data.
AB  - MOTIVATION: Microsatellites are among the most useful genetic markers in
      population biology. High-throughput sequencing of microsatellite-enriched
      libraries dramatically expedites the traditional process of screening recombinant
      libraries for microsatellite markers. However, sorting through millions of reads
      to distill high-quality polymorphic markers requires special algorithms tailored
      to tolerate sequencing errors in locus reconstruction, distinguish paralogous
      loci, rarify raw reads originating from the same amplicon and sort out various
      artificial fragments resulting from recombination or concatenation of auxiliary
      adapters. Existing programs warrant improvement. RESULTS: We describe a
      microsatellite prediction framework named HighSSR for microsatellite genotyping
      based on high-throughput sequencing. We demonstrate the utility of HighSSR in
      comparison to Roche gsAssembler on two Roche 454 GS FLX runs. The majority of the
      HighSSR-assembled loci were reliably mapped against model organism reference
      genomes. HighSSR demultiplexes pooled libraries, assesses locus polymorphism and
      implements Primer3 for the design of PCR primers flanking polymorphic
      microsatellite loci. As sequencing costs drop and permit the analysis of all
      project samples on next-generation platforms, this framework can also be used for
      direct simple sequence repeats genotyping. AVAILABILITY:
      http://code.google.com/p/highssr/

PMID- 22954627
TI  - Genome-wide in silico prediction of gene expression.
AB  - MOTIVATION: Modelling the regulation of gene expression can provide insight into
      the regulatory roles of individual transcription factors (TFs) and histone
      modifications. Recently, Ouyang et al. in 2009 modelled gene expression levels in
      mouse embryonic stem (mES) cells using in vivo ChIP-seq measurements of TF
      binding. ChIP-seq TF binding data, however, are tissue-specific and relatively
      difficult to obtain. This limits the applicability of gene expression models that
      rely on ChIP-seq TF binding data. RESULTS: In this study, we build regression
      based models that relate gene expression to the binding of 12 different TFs, 7
      histone modifications and chromatin accessibility (DNase I hypersensitivity) in
      two different tissues. We find that expression models based on computationally
      predicted TF binding can achieve similar accuracy to those using in vivo TF
      binding data and that including binding at weak sites is critical for accurate
      prediction of gene expression. We also find that incorporating histone
      modification and chromatin accessibility data results in additional accuracy.
      Surprisingly, we find that models that use no TF binding data at all, but only
      histone modification and chromatin accessibility data, can be as (or more)
      accurate than those based on in vivo TF binding data. AVAILABILITY AND
      IMPLEMENTATION: All scripts, motifs and data presented in this article are
      available online at
      http://research.imb.uq.edu.au/t.bailey/supplementary_data/McLeay2011a.

PMID- 22954628
TI  - Application and evaluation of automated methods to extract neuroanatomical
      connectivity statements from free text.
AB  - MOTIVATION: Automated annotation of neuroanatomical connectivity statements from
      the neuroscience literature would enable accessible and large-scale connectivity
      resources. Unfortunately, the connectivity findings are not formally encoded and
      occur as natural language text. This hinders aggregation, indexing, searching and
      integration of the reports. We annotated a set of 1377 abstracts for connectivity
      relations to facilitate automated extraction of connectivity relationships from
      neuroscience literature. We tested several baseline measures based on co
      occurrence and lexical rules. We compare results from seven machine learning
      methods adapted from the protein interaction extraction domain that employ part
      of-speech, dependency and syntax features. RESULTS: Co-occurrence based methods
      provided high recall with weak precision. The shallow linguistic kernel recalled
      70.1% of the sentence-level connectivity statements at 50.3% precision. Owing to
      its speed and simplicity, we applied the shallow linguistic kernel to a large set
      of new abstracts. To evaluate the results, we compared 2688 extracted connections
      with the Brain Architecture Management System (an existing database of rat
      connectivity). The extracted connections were connected in the Brain Architecture
      Management System at a rate of 63.5%, compared with 51.1% for co-occurring brain
      region pairs. We found that precision increases with the recency and frequency of
      the extracted relationships. AVAILABILITY AND IMPLEMENTATION: The source code,
      evaluations, documentation and other supplementary materials are available at
      http://www.chibi.ubc.ca/WhiteText. CONTACT: paul@chibi.ubc.ca. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics Online.

PMID- 22954629
TI  - MaConDa: a publicly accessible mass spectrometry contaminants database.
AB  - Mass spectrometry is widely used in bioanalysis, including the fields of
      metabolomics and proteomics, to simultaneously measure large numbers of molecules
      in complex biological samples. Contaminants routinely occur within these samples,
      for example, originating from the solvents or plasticware. Identification of
      these contaminants is crucial to enable their removal before data analysis, in
      particular to maintain the validity of conclusions drawn from uni- and
      multivariate statistical analyses. Although efforts have been made to report
      contaminants within mass spectra, this information is fragmented and its
      accessibility is relatively limited. In response to the needs of the
      bioanalytical community, here we report the creation of an extensive manually
      well-annotated database of currently known small molecule contaminants.
      AVAILABILITY: The Mass spectrometry Contaminants Database (MaConDa) is freely
      available and accessible through all major browsers or by using the MaConDa web
      service http://www.maconda.bham.ac.uk.

PMID- 22954630
TI  - SAPIN: a framework for the structural analysis of protein interaction networks.
AB  - SUMMARY: Protein interaction networks are widely used to depict the relationships
      between proteins. These networks often lack the information on physical binary
      interactions, and they do not inform whether there is incompatibility of
      structure between binding partners. Here, we introduce SAPIN, a framework
      dedicated to the structural analysis of protein interaction networks. SAPIN first
      identifies the protein parts that could be involved in the interaction and
      provides template structures. Next, SAPIN performs structural superimpositions to
      identify compatible and mutually exclusive interactions. Finally, the results are
      displayed using Cytoscape Web. AVAILABILITY: The SAPIN server is available at
      http://sapin.crg.es. CONTACT: jae-seong.yang@crg.eu or christina.kiel@crg.eu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      Online.

PMID- 22954631
TI  - Impact of ontology evolution on functional analyses.
AB  - MOTIVATION: Ontologies are used in the annotation and analysis of biological
      data. As knowledge accumulates, ontologies and annotation undergo constant
      modifications to reflect this new knowledge. These modifications may influence
      the results of statistical applications such as functional enrichment analyses
      that describe experimental data in terms of ontological groupings. Here, we
      investigate to what degree modifications of the Gene Ontology (GO) impact these
      statistical analyses for both experimental and simulated data. The analysis is
      based on new measures for the stability of result sets and considers different
      ontology and annotation changes. RESULTS: Our results show that past changes in
      the GO are non-uniformly distributed over different branches of the ontology.
      Considering the semantic relatedness of significant categories in analysis
      results allows a more realistic stability assessment for functional enrichment
      studies. We observe that the results of term-enrichment analyses tend to be
      surprisingly stable despite changes in ontology and annotation.

PMID- 22954632
TI  - Comb-p: software for combining, analyzing, grouping and correcting spatially
      correlated P-values.
AB  - SUMMARY: comb-p is a command-line tool and a python library that manipulates BED
      files of possibly irregularly spaced P-values and (1) calculates auto
      correlation, (2) combines adjacent P-values, (3) performs false discovery
      adjustment, (4) finds regions of enrichment (i.e. series of adjacent low P
      values) and (5) assigns significance to those regions. In addition, tools are
      provided for visualization and assessment. We provide validation and example uses
      on bisulfite-seq with P-values from Fisher's exact test, tiled methylation probes
      using a linear model and Dam-ID for chromatin binding using moderated t
      statistics. Because the library accepts input in a simple, standardized format
      and is unaffected by the origin of the P-values, it can be used for a wide
      variety of applications. AVAILABILITY: comb-p is maintained under the BSD
      license. The documentation and implementation are available at
      https://github.com/brentp/combined-pvalues. CONTACT: bpederse@gmail.com

PMID- 22954633
TI  - Mendel-GPU: haplotyping and genotype imputation on graphics processing units.
AB  - MOTIVATION: In modern sequencing studies, one can improve the confidence of
      genotype calls by phasing haplotypes using information from an external reference
      panel of fully typed unrelated individuals. However, the computational demands
      are so high that they prohibit researchers with limited computational resources
      from haplotyping large-scale sequence data. RESULTS: Our graphics processing unit
      based software delivers haplotyping and imputation accuracies comparable to
      competing programs at a fraction of the computational cost and peak memory
      demand. AVAILABILITY: Mendel-GPU, our OpenCL software, runs on Linux platforms
      and is portable across AMD and nVidia GPUs. Users can download both code and
      documentation at http://code.google.com/p/mendel-gpu/. CONTACT:
      gary.k.chen@usc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 22954635
TI  - Platelets in vascular disease.
AB  - Platelets play a key role in primary hemostasis and in the pathogenesis of
      atherosclerosis and atherothrombotic events such as stroke and myocardial
      infarction. When a plaque ruptures, platelets adhere to the underlying collagen
      matrix, become activated and aggregate, which may lead to vascular occlusions.
      Hemorheological aspects are intimately involved in this process. The assessment
      of this platelet function in vitro is difficult and has not reached the stage of
      routine use. Inhibition of platelet aggregation is the corner stone of any
      treatment of vascular disease. It is achieved mainly by to mechanisms, inhibition
      of thromboxane formation by acetylsalicylic acid, and with ADP receptor
      antagonists such as clopidogrel. Newer agents are being developed with the
      difficult mission to inhibit platelet aggregation more efficiently, and
      simultaneously reduce the risk of bleeding.

PMID- 22954634
TI  - Online reporting system for transfusion-related adverse events to enhance
      recipient haemovigilance in Japan: a pilot study.
AB  - BACKGROUND: A surveillance system for transfusion-related adverse reactions and
      infectious diseases in Japan was started at a national level in 1993, but current
      reporting of events in recipients is performed on a voluntary basis. A reporting
      system which can collect information on all transfusion-related events in
      recipients is required in Japan. METHODS: We have developed an online reporting
      system for transfusion-related events and performed a pilot study in 12 hospitals
      from 2007 to 2010. RESULTS: The overall incidence of adverse events per
      transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more
      adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma
      (0.93%). In addition, we found that the incidence of adverse events varied
      between hospitals according to their size and patient characteristics.
      CONCLUSION: This online reporting system is useful for collection and analysis of
      actual adverse events in recipients of blood transfusions and may contribute to
      enhancement of the existing surveillance system for recipients in Japan.

PMID- 22954636
TI  - Hemorheological parameters as independent predictors of venous thromboembolism.
AB  - The role played by hemorheological alterations in the development of deep vein
      thrombosis (DVT) has often been overlooked. Although marked rheological
      alterations and the relationship with thromboembolic events are well-defined in
      patients with hematological diseases such as myelom, Waldenstrom disease and
      polycythemia vera, the relationship is not so clear in patients without
      hematological diseases. In the present review, we analyzed studies evaluating the
      rheological profile in DVT patients. Among the cardiovascular risk factors, only
      hyperlipidemia, metabolic syndrome, tobacco and obesity increase DVT risk and, in
      addition, a disturbed rheological profile is shown which could further increase
      this risk. The significance of hematocrit and fibrinogen, the main factors
      influencing blood viscosity, is not sufficient to increase blood viscosity in any
      of the studies analyzed. DVT patients show increased fibrinogen levels and
      erythrocyte aggregation throughout all the studies despite patients not being in
      an acute reactant phase. In addition to rheological alterations, it is necessary
      to consider local conditions at pockets of venous valves which undergo
      deterioration with aging and play an important role equally to alterations in the
      rheological profile. Moreover, it is necessary to take into account that systemic
      rheological alterations are not comparable to those in low shear rate areas where
      minimum disturbances could be more relevant. It would be convenient to perform
      multicentric studies with the same rheological methodology and pre-analytical
      procedures to evaluate, in order to obviate the effect of thrombophilic and
      circumstantial risk factors, rheological parameters in patients with spontaneous
      DVT to elucidate their real contribution to the development of thromboembolic
      events.

PMID- 22954637
TI  - Clinical importance of antiplatelet drugs in cardiovascular diseases.
AB  - Platelets play an important role both in normal hemostasis and in pathological
      thrombus formation. Several large-scale clinical studies have proved that the
      inhibition of platelet aggregation results in a significant decrease in mortality
      and morbidity of ischemic atherothrombotic events, thus antiplatelet therapy
      became a key pharmacological method in prevention and treatment of such
      cardiovascular, cerebrovascular and peripheral arterial diseases. The present
      paper aims to give a brief overview of the most important antiplatelet drugs,
      their mechanism of action and their recommended usage in cardiovascular diseases.
      We also discuss possible methods to monitor the effectiveness of therapy and
      possible causes of therapeutic failure.

PMID- 22954638
TI  - Identification of CD133-, CD34- and KDR-positive cells in the bovine ovary: a new
      site of vascular wall resident endothelial progenitor cells.
AB  - Intense angiogenesis, vascular remodelling as well as regression of its
      vasculature are prerequisites for ovarian function with its cyclically developing
      and regressing follicles and corpora lutea. So far neither a stringent
      explanation for the enormous angiogenic potential of the ovary nor its cellular
      origins have been suggested. In an earlier study of our work group, endothelial
      cells were isolated from the bovine corpus luteum and cultivated in vitro. They
      performed vasulogenesis in vitro and showed properties of progenitor cells. The
      present study aimed at in situ identification of endothelial progenitor cells
      (EPCs) in the bovine ovary. Immunohistochemical examinations, based on the
      detection of KDR and CD34 co-labelled cells - a marker combination that amongst
      others is commonly accepted as typical for EPC identification - were performed.
      Hormonal cycle dependent expression varieties were analysed by the measurement of
      mRNA amounts of CD34 and KDR as well as the stem cell marker CD133 (Prominin-1).
      Ovarian samples comprising corpora lutea of varying stages (developing and mature
      corpus luteum, corpus luteum in regression, corpus luteum of pregnancy) from 17
      adult cows were examined. Results show that specific mRNA of CD133, CD34 and KDR
      was expressed in ovaries of all luteal stages. Expression data analysis revealed
      significant differences in CD133 and CD34 expression levels between the luteal
      stages but no significant differences in KDR expression. CD34/KDR co
      immunoreactive cells were predominantly situated within the media of arterial
      vessel wall. The detection of ovarian EPCs represents an important step towards
      further understanding of the mechanisms involved in the reproductive biology and
      pathophysiology of the ovary.

PMID- 22954639
TI  - Haemocompatibility testing of biomaterials using human platelets.
AB  - Cardiovascular implants are increasingly important in regenerative medicine. To
      improve the safety and function of blood-contacting implants a major need exists
      for new polymer-based biomaterials that avoid adverse reactions, particularly
      thrombotic events. This review is aimed to summarize the multi-stepped and
      interlinked processes leading to a thrombus growth on body foreign surfaces:
      protein adsorption, platelet adhesion accompanied by activation and spreading and
      the release of substances of various organelles activating other neighboured
      platelets (and the plasmatic coagulation) leading to the formation of a plug of
      platelets and, finally, to a thrombus.

PMID- 22954640
TI  - Potential mediators of adjustment for preschool children exposed to intimate
      partner violence.

PMID- 22954641
TI  - Five forms of childhood trauma: relationships with employment in adulthood.

PMID- 22954642
TI  - Effectiveness of educational materials designed to change knowledge and behavior
      about crying and shaken baby syndrome: a replication of a randomized controlled
      trial in Japan.
AB  - OBJECTIVES: Infant crying is particularly frustrating to caregivers in the first
      few months of life and the most common trigger for shaking and abuse. The
      effectiveness of the Period of PURPLE Crying prevention materials (DVD and
      booklet) designed to increase knowledge and change behaviors related to crying
      and the dangers of shaking was reported in North America. The aim of this study
      was to replicate the effectiveness of the PURPLE materials with mothers of
      newborns in Japan. METHODS: In a randomized controlled trial, 201 parents
      received either PURPLE materials or analogous control materials on infant safety
      via mail within 2 weeks of birth. At 6 weeks, mothers completed a 4-day
      behavioral diary. At 2 months, participants completed a predefined 20-min
      structured telephone survey by an independent firm to assess knowledge and
      behavior. RESULTS: Scores on crying knowledge scales (out of 100) were
      significantly higher in the intervention than control groups (56.1 vs. 53.1;
      difference=3.0, 95% confidence interval [CI]: 1.0-4.9, p<0.005). Percentage of
      sharing of advice to walk away if frustrated by crying was significantly higher
      in the intervention than control groups (22.4% vs. 4.1%; difference=18%, 95% CI:
      7.4-29.1). Walking away during unsoothable crying was significantly higher in the
      intervention group than controls (0.085 vs. 0.017 events per day, rate ratio=4.8,
      95% CI: 1.1-21.2) by diary. Self-talk behavior scale (out of 100) tended to
      significance in the intervention group (16.6 vs. 8.9, difference=7.7, 95% CI: 
      1.0 to 16.4, p<0.1). CONCLUSIONS: Crying knowledge, sharing of walk away
      information with others and walk away behavior when crying was unsoothable were
      higher for those who received intervention than control materials. The Period of
      PURPLE Crying materials may be useful in Japan as well as in North America for
      informing caregivers about the properties of infant crying and changing some
      behaviors related to infant crying and shaking. (UMIN Clinical Trials Registry
      register no. UMIN000001711.).

PMID- 22954643
TI  - Intervention for maltreating fathers: statistically and clinically significant
      change.
AB  - OBJECTIVE: Fathers are seldom the focus of efforts to address child maltreatment
      and little is currently known about the effectiveness of intervention for this
      population. To address this gap, we examined the efficacy of a community-based
      group treatment program for fathers who had abused or neglected their children or
      exposed their children to domestic violence. METHODS: Using a sample of 98 group
      participants, we examined the magnitude and clinical significance of pre- to post
      intervention changes in parenting, co-parenting and generalized aggression.
      RESULTS: Intervention led to considerable changes in fathers' over-reactivity to
      children's misbehavior and respect for their partner's commitment and judgment,
      with results being statistically significant, medium in size, moving mean scores
      into the normative range and with 36-43% of men who initially scored in the
      clinical range recovering by the end of intervention. Changes in other domains
      were also evident though of lesser magnitude. CONCLUSIONS: Although this study is
      limited in length of follow-up and the lack of a control group, results are
      promising for continued development of fathering interventions for this
      population of high-risk men.

PMID- 22954644
TI  - Cascade-mediated binding and bending of negatively supercoiled DNA.
AB  - Prokaryotes possess various defense mechanisms against invading DNA. Adaptive
      defense by CRISPR/Cas relies on incorporation of invader DNA sequences in the
      host genome. In Escherichia coli, processed transcripts of these incorporated
      sequences (crRNAs) guide Cascade-mediated invader DNA recognition. ( 1) (-) ( 4)
      Cascade is a multisubunit ribonucleoprotein complex, consisting of one crRNA and
      five proteins: Cse1, Cse2, Cas7, Cas5 and Cas6e. ( 1) (, ) ( 2) Cascade-mediated
      DNA recognition requires a conserved sequence adjacent to the target (protospacer
      adjacent motif, PAM) and a negatively supercoiled DNA topology. ( 3) (, ) ( 4)
      While Cse1 carries out PAM recognition, ( 5) the Cascade structure suggests that
      Cse2 may interact with target DNA in the PAM-distal end of the protospacer. ( 6)
      Using Electrophoretic Mobility Shift Assays, we here describe the function of the
      Cse1 and Cse2 subunits in the context of protospacer recognition on negatively
      supercoiled DNA. While Cse1 is required for nonspecific DNA binding, Cse2 appears
      to be important for specific binding, presumably by mediating stabilizing
      interactions with the displaced strand, the R-loop, or both. Furthermore, we
      performed Scanning Force Microscopy using linearized DNA molecules, which
      facilitates accurate and reliable measurements of Cascade-mediated bending. This
      analysis reveals that Cascade binding induces flexibility in the DNA target, most
      likely due to single stranded DNA regions flanking the R-loop.

PMID- 22954645
TI  - Effects of alcohol on the performance of the Tower of London task in relation to
      the menstrual cycle:  an electroencephalographic study.
AB  - It is well known that the metabolism of alcohol and cognitive functions can vary
      during the menstrual cycle. Also, both alcohol ingestion and hormonal variations
      during menstruation have been associated with characteristic changes in
      electroencephalographic (EEG) activity. The aim of the present study was to
      determine whether EEG activity during the performance of the Tower of London
      (TOL) task is affected by previous ingestion of alcohol and whether these EEG
      patterns vary in relation to different phases of the menstrual cycle. For this
      purpose, female participants consumed a moderate dose of alcohol or placebo
      during the follicular and early luteal phases of the menstrual cycle and then, 35
      min after liquid ingestion, EEG activity was recorded during the performance of
      TOL. A deleterious effect of alcohol on TOL performance was potentiated in the
      follicular phase, related to a higher alpha1 relative power, probably as a result
      of the low progesterone levels characteristic of this menstrual phase. These data
      show the feasibility of examining the interaction of alcohol and menstrual cycle
      phases on cognitive performance by means of EEG recording, and contribute toward
      a better understanding of the brain mechanisms that underlie the cognitive
      changes that occur during the menstrual cycle under the effects of alcohol.

PMID- 22954646
TI  - Evaluation of the endogenous cannabinoid system in mediating the behavioral
      effects of dipyrone (metamizol) in mice.
AB  - Dipyrone is a common nonopioid analgesic and antipyretic, which, in many
      countries, is available over the counter and is more widely used than paracetamol
      or aspirin. However, the exact mechanisms by which dipyrone acts remain
      inconclusive. Two novel arachidonoyl-conjugated metabolites are formed in mice
      following the administration of dipyrone that are dependent on the activity of
      fatty acid amide hydrolase (FAAH), which also represents the major catabolic
      enzyme of the endogenous cannabinoid ligand anandamide. These arachidonoyl
      metabolites not only inhibit cyclooxygenase (COX-1/COX-2) but also bind to
      cannabinoid receptors at low micromolar concentrations. The relative
      contributions of cannabinoid receptors and FAAH in the overall behavioral
      response to dipyrone remain untested. Accordingly, the two primary objectives of
      the present study were to determine whether the behavioral effects of dipyrone
      would (a) be blocked by cannabinoid receptor antagonists and (b) occur in FAAH
      mice. Here, we report that thermal antinociceptive, hypothermic, and locomotor
      suppressive actions of dipyrone are mediated by a noncannabinoid receptor
      mechanism of action and occurred after acute or repeated administration
      irrespective of FAAH. These findings indicate that FAAH-dependent arachidonoyl
      metabolites and cannabinoid receptors are not requisites by which dipyrone exerts
      these pharmacological effects under noninflammatory conditions.

PMID- 22954648
TI  - Advances in X-ray scattering: from solution SAXS to achievements with coherent
      beams.
AB  - Small-angle X-ray scattering (SAXS) of macromolecular systems in solution has
      become an obvious complement to high resolution structural studies. Using SAXS,
      structural hypotheses can be directly tested against experimental data in
      solution. Conformational changes or complex formation can be monitored, and help
      understanding structure-function relationships. Additionally, the reliability of
      the data has been much strengthened by on-line purification approaches. Moreover,
      when coherent X-rays are used for sample illumination, SAXS patterns become
      speckled and can provide electron-density maps directly by computational phase
      retrieval methods. Furthermore, X-ray free-electron laser with femtosecond pulse
      duration will enable us to take time-frozen images of biomolecules in solution
      free from radiation damage. In this paper, recent experimental and methodological
      advances in both classical and coherent SAXS are reviewed.

PMID- 22954647
TI  - Wavelength dependence of patman equilibration dynamics in phosphatidylcholine
      bilayers.
AB  - Assessment of the equilibration kinetics of Patman at the edges of its emission
      spectra provided additional insights about membrane properties beyond those
      obtained from end-point fluorescence measurements. Upon introduction of the probe
      to aqueous suspensions of liposomes, the emission intensity slowly increased
      about 10-fold (t(1/2)=~100 s). The rate of equilibration depended on emission
      wavelength, and was usually faster at 500 than at 435 nm. However, this trend was
      reversed for equilibration with lipids at their phase transition temperature. The
      apparent rotational motion of the dye also differed between the long and short
      emission wavelengths but did not display the slow equilibration time dependence
      observed with intensity measurements. These results suggested that slow
      equilibration reflects relaxation of the immediate membrane microenvironment
      around the probe rather than slow insertion into the membrane. The data were
      rationalized with a model that allows two membrane/probe configurations with
      distinct microenvironments. The analysis suggests that by monitoring the
      equilibration pattern of Patman, inferences can be made regarding the polarity of
      two microenvironments occupied by the probe, the distribution of the probe among
      those microenvironments, and the kinetics with which they relax to equilibrium.

PMID- 22954649
TI  - Cytolytic nanoparticles attenuate HIV-1 infectivity.
AB  - BACKGROUND: We investigated whether cytolytic melittin peptides could inhibit HIV
      1 infectivity when carried in a nanoparticle construct that might be used as a
      topical vaginal virucide. Free melittin and melittin-loaded nanoparticles were
      prepared and compared for cytotoxicity and their ability to inhibit infectivity
      by CXCR4 and CCR5 tropic HIV-1 strains. METHODS: TZM-bl reporter cells expressing
      luciferase under the control of the HIV-1 promoter were incubated with HIV-1 NLHX
      (CXCR4) or HIV-1 NLYU2 (CCR5) viral strains and different doses of soluble CD4
      (positive control) or free melittin to determine infectivity and viability.
      Melittin-loaded nanoparticles were formulated and different doses tested against
      VK2 vaginal epithelial cells to determine cell viability. Based on VK2 viability,
      melittin nanoparticles were tested for prevention of CXCR4 and CCR5 tropic HIV-1
      infectivity and viability of TZM-bl reporter cells. Low-speed centrifugation was
      used to compare the ability of blank non-melittin nanoparticles and melittin
      nanoparticles to capture CCR5 tropic HIV-1. RESULTS: As expected, the soluble CD4
      positive control inhibited CXCR4 (50% inhibitory concentration [IC50] 3.7 MUg/ml)
      and CCR5 (IC50 0.03 MUg/ml) tropic HIV-1 infectivity. Free melittin doses <2 MUM
      were not cytotoxic and were highly effective in reducing HIV-1 infectivity for
      both CXCR4 and CCR5 strains in TZM-bl reporter cells, while VK2 vaginal cell
      viability was adversely affected at all free melittin doses tested. However, VK2
      cell viability was not affected at any dose of melittin-loaded nanoparticles.
      Melittin nanoparticles safely and significantly decreased CXCR4 (IC50 2.4 MUM and
      IC90 6.9 MUM) and CCR5 (IC50 3.6 MUM and IC90 11.4 MUM) strain infectivity of TZM
      bl reporter cells. Furthermore, melittin nanoparticles captured more HIV-1 than
      blank nanoparticles. CONCLUSIONS: These data illustrate the first proof-of
      concept for therapeutic and safe nanoparticle-mediated inhibition of HIV-1
      infectivity. Future investigations appear warranted to explore the antiviral
      prophylactic potential of melittin nanoparticles to capture, disrupt and prevent
      initial infection with HIV-1 or potentially other enveloped viruses.

PMID- 22954650
TI  - Naturally prion resistant mammals: a utopia?
AB  - Each known abnormal prion protein (PrP (Sc) ) is considered to have a specific
      range and therefore the ability to infect some species and not others.
      Consequently, some species have been assumed to be prion disease resistant as no
      successful natural or experimental challenge infections have been reported. This
      assumption suggested that, independent of the virulence of the PrP (Sc)  strain,
      normal prion protein (PrP (C) ) from these 'resistant' species could not be
      induced to misfold. Numerous in vitro and in vivo studies trying to corroborate
      the unique properties of PrP (Sc)  have been undertaken. The results presented in
      the article "Rabbits are not resistant to prion infection" demonstrated that
      normal rabbit PrP (C) , which was considered to be resistant to prion disease,
      can be misfolded to PrP (Sc)  and subsequently used to infect and transmit a
      standard prion disease to leporids. Using the concept of species resistance to
      prion disease, we will discuss the mistake of attributing species specific prion
      disease resistance based purely on the absence of natural cases and incomplete in
      vivo challenges. The BSE epidemic was partially due to an underestimation of
      species barriers. To repeat this error would be unacceptable, especially if
      present knowledge and techniques can show a theoretical risk. Now that the myth
      of prion disease resistance has been refuted it is time to re-evaluate, using the
      new powerful tools available in modern prion laboratories, whether any other
      species could be at risk.

PMID- 22954651
TI  - [Follow-up study of respiratory nursing diagnoses in children with acute
      respiratory infection].
AB  - OBJECTIVE: To determine the baseline prevalence and incidence rates of Impaired
      Gas Exchange (IGE), Ineffective Airway Clearance (IAC) and Ineffective Breathing
      Pattern (IBP) in children with acute respiratory infection. METHOD: A prospective
      open cohort study was conducted in two public hospitals specialized in child care
      in the months from January to June of 2011. The sample consisted of 136 children
      with acute respiratory infection, which lasted a minimum of six and maximum of
      ten consecutive days. The data were collected through examination of the child
      and interviews with their parents. The diagnostic inference process was developed
      by trained nurses. RESULTS: The three diagnoses showed high rates at the
      beginning of follow-up period, with a reduction in the days after. There were
      similar rates of IBP and IGE. The temporal development of IBP was similar to that
      of IAC, but in lower proportions. Incidence rates in cases per 100 person / day
      were to IAC 39.28, 17.04 for DIG, and 13.31 for PRI. CONCLUSION: The three
      diagnoses studied appeared early and in high proportions. New cases of IAC appear
      more quickly when compared to the other two diagnoses.

PMID- 22954652
TI  - Phosphorus flux from wetland ditch sediments.
AB  - The accumulation of phosphorus (P) in the bottom sediment of field drainage
      ditches poses a threat to the ecology both of the ditch water and downstream
      water courses. We investigated the amounts, forms and internal loading of
      sediment-bound P along two drainage ditches that regulate water levels in a basin
      fen (~200 ha) supporting a mixture of restored wetland and drained agricultural
      fields. Water levels in the Lady's Drove Rhyne are currently managed to enhance
      the biodiversity of the wetland (Catcott Lows Reserve - an area formerly
      cultivated for arable crop production); whereas, the East Ditch is managed to
      drain adjoining land that remains under arable and livestock production.
      Laboratory-based chemical fractionation schemes were used to characterise the
      forms and potential mobility of the sediment-bound P, whilst pore-water
      equilibrators were employed in situ to evaluate the diffusive flux of P through
      the sediment-water column, and to characterise the corresponding redox
      conditions. Along both ditches, sediment pore-water profiles indicated conditions
      ranging from weakly to very reducing conditions with increasing depth, and net
      fluxes of P from the sediment to overlying water. P flux values ranged from 0.33
      to 1.30 mg m(-2) day(-1). Both the degree of P saturation (DPS) of the sediment
      and NaOH extractable (Fe/Al-bound) P correlated significantly (P<0.05) with P
      flux. Both in the wetland and agricultural ditches, by far the highest values for
      P flux were recorded at sites closest to points of drainage water entry from the
      corresponding, adjoining land. Although the P flux data were obtained from only a
      single sampling event, this study highlights the contribution of historical as
      well as ongoing agricultural land use on the sustained elevated P status of ditch
      sediments in lowland catchments.

PMID- 22954653
TI  - Accumulation of Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb in the otoliths and
      tissues of eel (Anguilla anguilla) following long-term exposure in an estuarine
      environment.
AB  - Aiming at increasing the resolution of otolith tracers, we investigated the
      possibility to use Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb otolith composition to
      retrieve the movements of eels (Anguilla anguilla) in the lower Gironde
      watershed. Caging experiments were designed to validate the site specific otolith
      signatures. Individually identified eels were reared in cages in three locations
      along the estuarine and river gradient. Three trials were set up for successive
      periods of 3 months and 6 months. Water Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb
      concentrations were monitored. The eel otolith composition corresponding to the
      experimental period was measured with an ICPMS coupled with a femtosecond laser.
      Liver Cd, Zn and Pb concentrations were measured. For each caging experiments, we
      tested the influence of individual weight gain, caging site and trial on
      elemental otolith concentrations. Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb were
      detected in eel otolith above the detection limits. Otolith Sr and Ba
      concentrations significantly discriminated the caging sites for one trial.
      Individual weight gain did not have a significant influence on otolith elemental
      concentrations. Co, Rb, Cd, Sn, Zn, Sr and Ba otolith concentrations were
      significantly influenced by the trials. Water elemental composition was only
      partly reflected by otolith elemental composition. The results showed that
      otolith composition had a more integrative value than water composition. Complex
      elemental seasonal variations and individual eel incorporation potential
      complicated the interpretation of otolith composition. Liver and otolith Cd and
      Zn concentrations did not show a statistically significant correlation.

PMID- 22954654
TI  - Mass and chemically speciated size distribution of Prague aerosol using an
      aerosol dryer--the influence of air mass origin.
AB  - Ambient aerosol particles dried using a diffusional aerosol dryer were sampled
      using a 7-stage modified Berner low pressure impactor with a back-up filter
      during the heating and non-heating season campaigns in 2008. The samples were
      analyzed for water-soluble ions and water-soluble organic carbon. Because of the
      drying, the aerosol size distribution was not influenced by the daily variability
      of ambient relative humidity. The results summarize the observations from
      campaigns in both the heating (11 sampling days) and non-heating (10 sampling
      days) seasons. The aerosols sampled on individual days were classified based on
      the connected air mass back trajectories into three classes: sea-influenced
      aerosol (SIA), continental aerosol (CA) and mixed aerosol (MA) for samples of
      intermediate origin. The differences between CA and SIA were substantial both
      when looking at the normalized mass size distributions of the particulate matter
      (PM) and of the individual species and when taking into account the absolute
      concentrations in the fine and coarse size fractions. The main differences were
      found in the normalized mass size distributions of the PM and of the sea-salt
      related ions.

PMID- 22954655
TI  - Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass
      vaccination campaign and observational cohort study.
AB  - BACKGROUND: Zanzibar, in east Africa, has been severely and repeatedly affected
      by cholera since 1978. We assessed the effectiveness of oral cholera vaccination
      in high-risk populations in the archipelago to estimate the indirect (herd)
      protection conferred by the vaccine and direct vaccine effectiveness. METHODS: We
      offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals
      aged 2 years and older in six rural and urban sites. To estimate vaccine direct
      protection, we compared the incidence of cholera between recipients and non
      recipients using generalised estimating equations with the log link function
      while controlling for potential confounding variables. To estimate indirect
      effects, we used a geographic information systems approach and assessed the
      association between neighbourhood-level vaccine coverage and the risk for cholera
      in the non-vaccinated residents of that neighbourhood, after controlling for
      potential confounding variables. This study is registered with
      ClinicalTrials.gov, number NCT00709410. FINDINGS: Of 48,178 individuals eligible
      to receive the vaccine, 23,921 (50%) received two doses. Between February, 2009,
      and May, 2010, there was an outbreak of cholera, enabling us to assess vaccine
      effectiveness. The vaccine conferred 79% (95% CI 47-92) direct protection against
      cholera in participants who received two doses. Indirect (herd) protection was
      shown by a decrease in the risk for cholera of non-vaccinated residents within a
      household's neighbourhood as the vaccine coverage in that neighbourhood
      increased. INTERPRETATION: Our findings suggest that the oral cholera vaccine
      offers both direct and indirect (herd) protection in a sub-Saharan African
      setting. Mass oral cholera immunisation campaigns have the potential to provide
      not only protection for vaccinated individuals but also for the unvaccinated
      members of the community and should be strongly considered for wider use. Because
      this is an internationally-licensed vaccine, we could not undertake a randomised
      placebo-controlled trial, but the absence of vaccine effectiveness against non
      cholera diarrhoea indicates that the noted protection against cholera could not
      be explained by bias. FUNDING: Bill & Melinda Gates Foundation, Swedish
      International Development Cooperation Agency, and the South Korean Government.

PMID- 22954656
TI  - A case for control of cholera in Africa by vaccination.

PMID- 22954658
TI  - Sexual selection in prehistoric animals: detection and implications.
AB  - Many fossil animals bear traits such as crests or horns that probably functioned
      as sexually selected signals or weapons. Interpretations of these structures as
      functioning in mate choice or intrasexual contests are often controversial, with
      interpretations based on biomechanics or physiology being favoured by many.
      Although testing hypotheses based on sexual selection can be difficult,
      especially given that there is no single, reliable means of recognising sexual
      selection, we argue that it is not impossible; indeed, there are now several
      cases where sexual selection is strongly supported. In other cases, a careful
      study of features such as sexual dimorphism, ontogeny, and allometry, coupled
      with testing of alternative hypotheses, will be necessary to distinguish between
      possible explanations for exaggerated features.

PMID- 22954660
TI  - Structural insights into transcriptional repression by noncoding RNAs that bind
      to human Pol II.
AB  - Gene transcription is regulated in response to environmental changes and
      developmental cues. In mammalian cells subjected to stress conditions such as
      heat shock, transcription of most protein-coding genes decreases, while the
      transcription of heat shock protein genes increases. Repression involves direct
      binding to RNA polymerase II (Pol II) of certain noncoding RNAs (ncRNAs) that are
      upregulated upon heat shock. Another class of ncRNAs is also upregulated and
      binds to Pol II but does not inhibit transcription. Incorporation of repressive
      ncRNAs into pre-initiation complexes prevents transcription initiation, while non
      repressive ncRNAs are displaced from Pol II by TFIIF. Here, we present cryo
      electron microscopy reconstructions of human Pol II in complex with six different
      ncRNAs from mouse and human. Our structures show that both repressive and non
      repressive ncRNAs bind to a conserved binding site within the cleft of Pol II.
      The site, which is also shared with a previously characterized yeast aptamer, is
      close to the active center and, thus, in an ideal position to regulate
      transcription. Importantly, additional RNA elements extend flexibly beyond the
      docking site. We propose that the differences concerning the repressive activity
      of the ncRNAs analyzed must be due to the distinct character of these more
      unstructured, flexible segments of the RNA that emanate from the cleft.

PMID- 22954661
TI  - Telomerase activity is sensitive to subtle perturbations of the TLC1 pseudoknot
      3' stem and tertiary structure.
AB  - Pseudoknot formation in the core region of the telomerase RNA has been
      demonstrated to be important for telomerase activity in vertebrates, ciliates,
      and yeast. Characterization of the Saccharomyces cerevisiae telomerase RNA (TLC1)
      pseudoknot identified tertiary structural interactions that are also important
      for telomerase activity, as previously observed for the Kluyveromyces lactis and
      human telomerase RNA pseudoknots. In addition, the contributions of backbone
      ribose 2'-OH groups in the pseudoknot to telomerase catalysis were investigated
      previously, using 2'-OH (ribose) to 2'-H (deoxyribose) or 2'-O-methyl
      substitutions in the stem 2 helix, and it was proposed that one or more 2'-OH
      groups from the stem 2 sequences at or near the triple helix participate in
      telomerase catalysis. Based on these studies and investigations of the structural
      and thermodynamic properties of the TLC1 RNA pseudoknot region, we have examined
      the structural and thermodynamic perturbations of the 2'-O-methyl and 2'-H
      substituted pseudoknots, using UV-monitored thermal denaturation, native gel
      electrophoresis, and circular dichroism spectroscopy. Our results demonstrate the
      presence of A-form helical geometry perturbations in the backbone sugar
      substituted pseudoknots, show a correlation between thermodynamic stability and
      telomerase activity, and are consistent with the identification of the U809
      ribose 2'-OH as a potential contributor to telomerase activity.

PMID- 22954662
TI  - Histone recognition by human malignant brain tumor domains.
AB  - Histone methylation has emerged as an important covalent modification involved in
      a variety of biological processes, especially regulation of transcription and
      chromatin dynamics. Lysine methylation is found in three distinct states
      (monomethylation, dimethylation and trimethylation), which are recognized by
      specific protein domains. The malignant brain tumor (MBT) domain is one such
      module found in several chromatin regulatory complexes including Polycomb
      repressive complex 1. Here, we present a comprehensive characterization of the
      human MBT family with emphasis on histone binding specificity. SPOT-blot peptide
      arrays were used to screen for the methyllysine-containing histone peptides that
      bind to MBT domains found in nine human proteins. Selected interactions were
      quantified using fluorescence polarization assays. We show that all MBT proteins
      recognize only monomethyllysine and/or dimethyllysine marks and provide evidence
      that some MBT domains recognize a defined consensus sequence while others bind in
      a promiscuous, non-sequence-specific manner. Furthermore, using structure-based
      mutants, we identify a triad of residues in the methyllysine binding pocket that
      imparts discrimination between monomethyllysine and dimethyllysine. This study
      represents a comprehensive analysis of MBT substrate specificity, establishing a
      foundation for the rational design of selective MBT domain inhibitors that may
      enable elucidation of their role in human biology and disease.

PMID- 22954663
TI  - Renal blood flow, fractional excretion of sodium and acute kidney injury:  time
      for a new paradigm?
AB  - PURPOSE OF REVIEW: Global renal blood flow is considered pivotal to renal
      function. Decreased global renal blood flow (decreased perfusion) is further
      considered the major mechanism of reduced glomerular filtration rate responsible
      for the development of acute kidney injury (AKI) in critically ill patients.
      Additionally, urinary biochemical tests are widely taught to allow the
      differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI
      (so-called acute tubular necrosis)]. In this review we will examine recent
      evidence regarding these two key clinical paradigms. RECENT FINDINGS: Recent
      animal experiments and clinical studies in humans using cine-phase contrast
      magnetic resonance technology are not consistent with the decreased perfusion
      paradigm. They suggest instead that changes in the intra-renal circulation
      including modification in efferent arteriolar function and intra-renal shunting
      are much more likely to be responsible for AKI, especially in sepsis. Similarly,
      recent human studies indicate the urinary biochemistry has limited diagnostic or
      prognostic ability and is dissociated form biomarker and microscopic evidence of
      tubular injury. SUMMARY: Intra-renal microcirculatory changes are likely more
      important than changes in global blood flow in the development of AKI. Urinary
      biochemistry is not a clinically useful diagnostic or prognostic tool in
      critically ill patients at risk of or with AKI.

PMID- 22954664
TI  - International comparisons of intensive care:  informing outcomes and improving
      standards.
AB  - PURPOSE OF REVIEW: Interest in international comparisons of critical illness is
      growing, but the utility of these studies is questionable. This review examines
      the challenges of international comparisons and highlights areas in which
      international data provide information relevant to clinical practice and resource
      allocation. RECENT FINDINGS: International comparisons of ICU resources
      demonstrate that definitions of critical illness and ICU beds vary due to
      differences in ability to provide organ support and variable staffing. Despite
      these limitations, recent international data provide key information to
      understand the pros and cons of different availability of ICU beds on patient
      flow and outcomes, and also highlight the need to ensure long-term follow-up due
      to heterogeneity in discharge practices for critically ill patients. With
      increasing emphasis on curbing costs of healthcare, systems that deliver lower
      cost care provide data on alternative options, such as regionalization, flexible
      allocation of beds, and bed rationing. SUMMARY: Differences in provision of
      critical care can be leveraged to inform decisions on allocation of ICU beds,
      improve interpretation of clinical outcomes, and assess ways to decrease costs of
      care. International definitions of key components of critical care are needed to
      facilitate research and ensure rigorous comparisons.

PMID- 22954665
TI  - A double-blind, randomised, placebo-controlled, phase 2b study evaluating
      sorafenib in combination with paclitaxel as a first-line therapy in patients with
      HER2-negative advanced breast cancer.
AB  - BACKGROUND: We conducted a phase 2b, randomised, double-blind, placebo-controlled
      screening trial to evaluate the addition of the multikinase inhibitor sorafenib
      (antiproliferative/antiangiogenic) to first-line paclitaxel for human epidermal
      growth factor receptor 2 (HER2)-negative locally recurrent/metastatic breast
      cancer. METHODS: Patients were randomised to paclitaxel (90mg/m(2), weekly,
      intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily)
      or placebo. The primary endpoint was progression-free survival (PFS). A sample
      size of 220 patients was planned with relative risk <= 0.82 (1-sided alpha=0.14)
      after 120 events supporting a treatment effect. FINDINGS: Patients were
      randomised in India (n=170), the United States (n=52) and Brazil (n=15). Median
      PFS was 6.9 months for sorafenib versus 5.6 months for placebo (hazard ratio
      (HR)=0.788; 95% confidence interval (CI), 0.558-1.112; P=0.1715 [1-sided
      P=0.0857]). The addition of sorafenib increased time to progression (median, 8.1
      versus 5.6 months; HR=0.674; 95% CI 0.465-0.975; P=0.0343) and improved overall
      response (67% versus 54%; P=0.0468). Overall survival did not statistically
      differ (median, 16.8 versus 17.4 months; HR=1.022; 95% CI 0.715-1.461; P=0.904).
      Grade 3/4 toxicities (sorafenib versus placebo) included hand-foot skin reaction
      (31% versus 3%), neutropenia (13% versus 7%) and anaemia (11% versus 6%). Two
      treatment-related deaths occurred (malaria and liver dysfunction) in the
      sorafenib arm. INTERPRETATION: The addition of sorafenib to paclitaxel improved
      disease control but did not significantly improve PFS to support a phase 3 trial
      of similar design. Toxicity of the combination was manageable with dose
      reductions.

PMID- 22954667
TI  - Age-related changes of hippocampal synaptic plasticity in AbetaPP-null mice are
      restored by NGF through p75NTR.
AB  - Amyloid-beta protein precursor (AbetaPP) is a ubiquitous protein found in all
      cell types, suggesting basic and yet important roles, which still remain to be
      fully elucidated. Loss of function of AbetaPP has been linked to abnormal
      neuronal morphology and synaptic function within the hippocampus and alterations
      in spatial learning, suggesting a neurotrophic role for this protein. Besides
      AbetaPP, nerve growth factor (NGF) and other neurotrophins have also been shown
      to finely modulate neuronal excitability, synaptic plasticity, and cognitive
      functions. In addition, recent data support the hypothesis of a functional
      interconnection between AbetaPP and NGF pathway. Here, we demonstrated that loss
      of AbetaPP function, leading to progressive decrease of choline acetyltransferase
      expression in the septum, correlates with age-related impairment of long-term
      potentiation (LTP) in the dentate gyrus. We next addressed whether impaired
      hippocampal plasticity in AbetaPP-null mice can be restored upon NGF treatment.
      Notably, NGF, as well as Pro-NGF, can fully revert LTP deficits in AbetaPP-null
      mice through p75NTR and JNK pathway activation. Overall the present study may
      unveil a new mechanism by which, in the absence of AbetaPP, NGF treatment may
      preferentially direct p75-neurotrophin-dependent JNK activation toward
      regeneration and plasticity in functionally relevant brain circuits.

PMID- 22954666
TI  - Influence of semi-quantitative oestrogen receptor expression on adjuvant
      endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study
      analysis.
AB  - BACKGROUND: Multiple studies suggest better efficacy of chemotherapy in invasive
      ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC).
      However, data on efficacy of adjuvant endocrine therapy regimens and histological
      subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and
      ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by
      Allred score was also investigated. METHODS: Dutch and Belgian patients enrolled
      in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized
      to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years.
      Inclusion was restricted to IDC and ILC patients. Histological subtype was
      assessed locally; ER expression was centrally reviewed according to Allred score
      (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free
      survival (RFS), which was the time from randomization to disease relapse.
      FINDINGS: Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS
      was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for
      exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69
      (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich
      Allred scores allocated to exemestane alone had an improved RFS (multivariable HR
      0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores
      allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32
      4.11)). Significant effect modification by ER-Allred score was confirmed
      (multivariable p=0.003). INTERPRETATION: Efficacy of endocrine therapy regimens
      was similar for IDC and ILC. However, ER-rich patients showed superior efficacy
      to upfront exemestane, while ER-poor patients had better outcomes with sequential
      therapy, irrespective of histological subtype, emphasising the relevance of
      quantification of ER expression.

PMID- 22954668
TI  - CNP and DPYSL2 mRNA expression and promoter methylation levels in brain of
      Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is a highly prevalent type of dementia in the elderly
      population. AD is a complex neurodegenerative disorder. Thus, epigenetic
      mechanisms that regulate gene expression might have an important role in AD. CNP
      (2',3'-Cyclic Nucleotide 3' Phosphodiesterase) gene encodes a protein used as an
      index of myelin alterations. DPYSL2 (Dihydropyrimidinase-like 2) is described as
      acting in structural and regulatory processes in the central nervous system, such
      as neural differentiation, neurotransmitter release, and stabilization of
      microtubules. In this study, we evaluated gene expression and epigenetic
      regulation of CNP and DPYSL2 genes in three postmortem brain regions (entorhinal
      and auditory cortices and hippocampus) of AD patients and healthy elderly
      controls. mRNA quantification was performed using qRT-PCR, and promoter DNA
      methylation patterns were determined by mass spectrometry using the Sequenom
      EpiTYPER platform. We observed CNP mRNA downregulation in entorhinal and auditory
      cortex in relation to the same regions of the control group. CNP alterations in
      the brain might suggest impairment in myelination leading to a synaptic and
      cognition loss. No AD-associated differences in CNP and DPYSL2 promoter DNA
      methylation were observed, suggesting that other mechanisms may be involved in
      mediating the observed CNP gene expression.

PMID- 22954669
TI  - Recognition of facial emotional expression in amnestic mild cognitive impairment.
AB  - We examined whether recognition of facial emotional expression would be affected
      in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met
      the initial inclusion criteria; 10 were subsequently excluded (Geriatric
      Depression Score > 5). 22 subjects were classified with aMCI based on published
      criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n
      = 12); 18 subjects were cognitively normal. All underwent standard neurological
      and neuropsychological evaluations as well as tests of facial emotion recognition
      (FER) and famous faces identification (FFI). Among normal controls, FFI was
      negatively correlated with Mini-Mental Status Examination scores and positively
      correlated with executive function. Among patients with aMCI, FER was correlated
      with attention/speed of processing. No other correlations were significant. In a
      multinomial logistic regression model adjusted for age, gender, and education, a
      poorer score on FER, but not on FFI, was associated with greater odds of being
      classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05
      13.91; p = 0.042). This association was not explained by memory or global
      cognitive score. There was no association between FER or FFI and SD-aMCI (OR,
      1.13; 95% CI, 0.36-3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired
      in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve
      segregated neurocognitive networks.

PMID- 22954670
TI  - Anti-ATP synthase autoantibodies induce neuronal death by apoptosis and impair
      cognitive performance in C57BL/6J mice.
AB  - Previous studies have suggested a pathogenetic role of autoantibodies (Abs)
      against ATP synthase (ATPs) in patients with Alzheimer's disease (AD). Using a
      mouse model, we found that intracerebroventricular administration of anti-ATPs
      Abs, purified from AD patients, leads to poor cognitive performance and
      pronounced cell damage in the hippocampus, a brain region specifically involved
      in learning and memory processes, which is severely affected in AD. Our results
      are suggestive of a role of anti-ATPs-Abs in the onset and progression of AD and
      also provide a fruitful model for the study of memory disturbances in
      neurodegenerative diseases.

PMID- 22954671
TI  - Diminished parkin solubility and co-localization with intraneuronal amyloid-beta
      are associated with autophagic defects in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an aging disorder characterized by amyloid-beta
      (Abeta) accumulation in extracellular plaques and formation of intracellular
      tangles containing hyperphosphorylated tau (p-Tau). Autophagic defects, leading
      to accumulation of autophagosomes, are recognized in AD. Parkin is an E3
      ubiquitin ligase involved in degradation of proteins via autophagy and the
      proteasome. We investigated the role of parkin in postmortem brain tissues from
      21 AD patients and 15 control subjects. We detected decreased parkin solubility
      in AD cortex and parkin co-localization with intraneuronal Abeta(1-42) in the
      hippocampus and cortex of AD patients. Parkin accumulation with intraneuronal
      Abeta and p-Tau was detected in autophagosomes in AD brains. To determine the
      role of parkin in Abeta clearance, we generated gene transfer animals expressing
      lentiviral Abeta(1-42)with and without parkin and examined autophagic mechanisms.
      Lentiviral expression of Abeta(1-42) led to p-Tau accumulation and induced
      autophagic defects, leading to accumulation of autophagic vacuoles. However, co
      expression of wild type parkin facilitated autophagic clearance and promoted
      deposition of Abeta(1-42) and p-Tau into the lysosome. Taken together, these data
      suggest that Abeta(1-42) alters normal autophagy and parkin enhances autophagic
      clearance. In conclusion, decreased parkin solubility may lead to co-localization
      with intraneuronal Abeta(1-42) and compromise the cell autophagic clearance
      ability. Parkin may clear autophagic defects via autophagosome degradation.

PMID- 22954672
TI  - Direct renin inhibition modulates insulin resistance in caveolin-1-deficient
      mice.
AB  - OBJECTIVE: To test the hypothesis that aliskiren improves the metabolic phenotype
      in a genetic mouse model of the metabolic syndrome (the caveolin-1 (cav-1) knock
      out (KO) mouse). MATERIALS/METHODS: Eleven-week-old cav-1 KO and genetically
      matched wild-type (WT) mice were randomized to three treatment groups: placebo
      (n=8/group), amlodipine (6 mg/kg/day, n=18/ group), and aliskiren (50 mg/kg/day,
      n=18/ group). After three weeks of treatment, all treatment groups were assessed
      for several measures of insulin resistance (fasting insulin and glucose, HOMA-IR,
      and the response to an intraperitoneal glucose tolerance test (ipGTT)) as well as
      for triglyceride levels and the blood pressure response to treatment. RESULTS:
      Treatment with aliskiren did not affect the ipGTT response but significantly
      lowered the HOMA-IR and insulin levels in cav-1 KO mice. However, treatment with
      amlodipine significantly degraded the ipGTT response, as well as the HOMA-IR and
      insulin levels in the cav-1 KO mice. Aliskiren also significantly lowered
      triglyceride levels in the cav-1 KO but not in the WT mice. Moreover, aliskiren
      treatment had a significantly greater effect on blood pressure readings in the
      cav-1 KO vs. WT mice, and was marginally more effective than amlodipine.
      CONCLUSIONS: Our results support the hypothesis that aliskiren reduces insulin
      resistance as indicated by improved HOMA-IR in cav-1 KO mice whereas amlodipine
      treatment resulted in changes consistent with increased insulin resistance. In
      addition, aliskiren was substantially more effective in lowering blood pressure
      in the cav-1 KO mouse model than in WT mice and marginally more effective than
      amlodipine.

PMID- 22954673
TI  - Heme modulates smooth muscle cell proliferation and migration via NADPH oxidase:
      a counter-regulatory role for heme oxygenase system.
AB  - Accumulation of vascular smooth muscle cells (VSMC) in response to inflammatory
      stimuli is a key event in atherogenesis, which commonly occurs in sinuous vessels
      with turbulent blood flow what leads to hemolysis and consequent free heme
      accumulation, a known pro-oxidant and pro-inflammatory molecule. In this work, we
      investigated the effects of free heme on VSMC, and the molecular mechanisms
      underlying this process. Free heme induces a concentration-dependent migration
      and proliferation of VSMC which depends on the production of reactive oxygen
      species (ROS) derived from NADPH oxidase (NADPHox) activity. Additionally, heme
      activates redox-sensitive proliferation-related signaling routes, such as mitogen
      activated protein kinase (MAPK) and NF-kappaB, and induces heme oxygenase-1 (HO
      1) expression. NADPHox-dependent proliferative effect of heme seems to be
      endogenously modulated by HO since the pretreatment of VSMC with HO inhibitors
      potentiates heme-induced proliferation and, in parallel, increases ROS
      production. These effects were no longer observed in the presence of heme
      metabolites, carbon monoxide and biliverdin. The data indicate that VSMC
      proliferation induced by heme is endogenously modulated by a critical counter
      regulatory crosstalk between NADPHox and HO systems.

PMID- 22954674
TI  - Dietary treatment with rice containing resistant starch improves markers of
      endothelial function with reduction of postprandial blood glucose and oxidative
      stress in patients with prediabetes or newly diagnosed type 2 diabetes.
AB  - OBJECTIVE: We aimed to evaluate whether 4-week of dietary treatment with rice
      containing resistant starch reduces blood glucose and oxidative stress as well as
      improves endothelial function. METHODS: Patients with impaired fasting glucose
      (IFG), impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes (n =
      90) were randomly assigned to either a group ingesting rice containing 6.51 g
      resistant starch daily or a control rice group for 4-weeks. We assessed fasting
      and postprandial levels of glucose and insulin, oxidative stress markers and
      endothelial function using reactive hyperemia peripheral arterial tonometry (RH
      PAT). RESULTS: The diet containing rice with resistant starch reduced fasting
      insulin and insulin resistance, postprandial glucose (P = 0.010) and insulin
      levels at 30 min, and glucose and insulin areas under the response curve after
      the standard meal. Rice with resistant starch also decreased urinary 8-epi
      PGF(2alpha) and plasma malondialdehyde (MDA) and increased the RH-PAT index (P <
      0.001) and total nitric oxide (NO). Postprandial changes in glucose at 60 and 120
      min and areas under the glucose response curve, MDA, RH-PAT, and total NO of the
      test group differed significantly from those in the control even after adjusting
      for baseline values. Overall, changes in the RH-PAT index correlated positively
      with changes in total NO (r = 0.336, P = 0.003) and superoxide dismutase activity
      (r = 0.381, P = 0.001) and negatively with changes in MDA (r = -0.358, P = 0.002)
      and 8-epi-PGF(2alpha). CONCLUSIONS: In patients with IFG, IGT or newly diagnosed
      type 2 diabetes, 4-weeks of dietary treatment with rice containing resistant
      starch was associated with improved endothelial function with reduction of
      postprandial glucose and oxidative stress compared with control.

PMID- 22954676
TI  - Determination of mepiquat chloride in cotton crops and soil and its dissipation
      rates.
AB  - A simple, accurate and highly sensitive analytical method was developed in this
      study for determining the residues and dissipation dynamics of mepiquat chloride
      in soil and cotton crops (including plant and seed). The samples in this method
      were directly extracted with methanol-ammonium acetate solution and followed by
      analysis of high performance liquid chromatography tandem mass spectrometry (HPLC
      MS/MS). The intra-day and inter-day recoveries of mepiquat chloride were in the
      range of 76.58-98.87 percent and 73.48-104.7 percent with relative standard
      deviations (RSDs) of 0.89-5.04 percent and 3.84-10.7 percent, respectively. The
      limit of quantification (LOQ) was 0.05mgkg(-1) for soil and 0.1mgkg(-1) for
      cotton plant and seed. The half-life of mepiquat chloride in cotton plants and in
      soil was 2.51-3.85 days and 7.56-10.50 days, respectively. The final residues of
      mepiquat chloride in all cotton seeds were below the MRLs of EU (5mgkg(-1)),
      Japan and America (2mgkg(-1)) over 14 days after the last spraying, and were
      below 1mgkg(-1) (the MRLs set by Argentina and Australia) over 21 days after the
      last spraying at recommended dosage. The final residues in soil were below the
      LOD (0.01mgkg(-1)) over 21 days after the last spraying.

PMID- 22954675
TI  - Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor
      expression during fasting in normolipidemic hamsters.
AB  - BACKGROUND: PCSK9 has emerged as a key regulator of serum LDL-C metabolism by
      promoting the degradation of hepatic LDL receptor (LDLR). In this study, we
      investigated the effect of fasting on serum PCSK9, LDL-C, and hepatic LDLR
      expression in hamsters and further delineated the molecular pathways involved in
      fasting-induced repression of PCSK9 transcription. RESULTS: Fasting had
      insignificant effects on serum total cholesterol and HDL-C levels, but reduced
      LDL-C, triglyceride and insulin levels. The decrease in serum LDL-C was
      accompanied by marked reductions of hepatic PCSK9 mRNA and serum PCSK9 protein
      levels with concomitant increases of hepatic LDLR protein amounts. Fasting
      produced a profound impact on SREBP1 expression and its transactivating activity,
      while having modest effects on mRNA expressions of SREBP2 target genes in hamster
      liver. Although PPARalpha mRNA levels in hamster liver were elevated by fasting,
      ligand-induced activation of PPARalpha with WY14643 compound in hamster primary
      hepatocytes did not affect PCSK9 mRNA or protein expressions. Further
      investigation on HNF1alpha, a critical transactivator of PCSK9, revealed that
      fasting did not alter its mRNA expression, however, the protein abundance of
      HNF1alpha in nuclear extracts of hamster liver was markedly reduced by prolonged
      fasting. CONCLUSION: Fasting lowered serum LDL-C in hamsters by increasing
      hepatic LDLR protein amounts via reductions of serum PCSK9 levels. Importantly,
      our results suggest that attenuation of SREBP1 transactivating activity owing to
      decreased insulin levels during fasting is primarily responsible for compromised
      PCSK9 gene transcription, which was further suppressed after prolonged fasting by
      a reduction of nuclear HNF1alpha protein abundance.

PMID- 22954677
TI  - The effect of extracellular conductivity on electroporation-mediated molecular
      delivery.
AB  - In this work, the effect of extra-cellular conductivity on electroporation
      mediated molecular delivery efficiency is investigated. A numerical model
      combining the Smoluchowski equation for membrane permeabilization and the Nernst
      Planck equations for ion transport is used to simulate the evolution of ion
      concentration spatially and temporally. The results are compared with and used to
      interpret trends observed from previous experimental measurements. Agreements are
      found which suggest the critical importance of electrophoretic transport. This
      mechanism controls delivery efficiency on the quantitative level. Meanwhile, a
      simple formula is developed to predict the molecular content delivered via
      electrophoresis. The formula can be used as a compact model which provides good
      approximation to the full numerical model while avoiding the computational cost.

PMID- 22954678
TI  - A rare Cryptosporidium parvum genotype associated with infection of lambs and
      zoonotic transmission in Italy.
AB  - An outbreak of cryptosporidiosis occurred in a mixed sheep/cattle farm of Central
      Italy in October 2011. A total of 450 ovines (250 sheep and 200 lambs) and 140
      bovines (130 cows and 10 calves) were housed in two separated units, at the time
      of the outbreak. About half of the lambs had diarrhea due to Cryptosporidium sp.
      with a mortality rate of 80%; calves were not infected. Genomic DNA was extracted
      from an archived slide and from fecal specimens, and the parasite was identified
      as Cryptosporidium parvum by PCR and sequence analysis at the CpA135 gene.
      Genotyping at the GP60 gene showed the presence of a very rare genotype,
      IIaA20G2R1. Shortly after the outbreak was identified, the son of the farm's
      owner, aged 18 months, experienced an acute gastroenteritis and was hospitalized
      due to recurrent episodes of diarrhea, fever, vomiting and lack of appetite. The
      feces tested negative for bacteria and viruses, whereas cryptosporidiosis was
      diagnosed by microscopy and an immunochromatographic test. Molecular typing
      identified the C. parvum genotype IIaA20G2R1 in the feces of the child. This is
      the first case of transmission of cryptosporidiosis in Italy involving lambs as
      source of oocysts infectious to humans.

PMID- 22954679
TI  - Estrogen and telomerase in human peripheral blood mononuclear cells.
AB  - The enzyme telomerase plays an important role in sustaining the capacity of T
      lymphocytes for homeostatic replication. Recent data have suggested that gonadal
      steroids might modulate telomerase expression or activity within these cells. We
      used quantitative assay techniques for both telomerase mRNA expression and
      telomerase enzymatic activity to systematically examine the effects of
      physiologic concentrations of estradiol on human peripheral blood mononuclear
      cells under basal conditions and under conditions that normally enhance
      telomerase activity in T lymphocytes. Cells from women tended to exhibit higher
      responsiveness of telomerase activity to induction by T cell receptor engagement.
      However, we found no evidence of a direct effect of physiologic concentrations of
      estradiol on human telomerase reverse transcriptase (hTERT) mRNA expression,
      hTERT protein expression, or telomerase enzymatic activity in cultured PBMCs.
      While estrogen might exert developmental effects on T cells to alter telomerase
      responsiveness to T cell receptor engagement, mature peripheral T cells do not
      respond to estradiol with changes in expression or function of telomerase.

PMID- 22954680
TI  - Normal testicular function without detectable follicle-stimulating hormone. A
      novel mutation in the follicle-stimulating hormone receptor gene leading to
      apparent constitutive activity and impaired agonist-induced desensitization and
      internalization.
AB  - Activating mutations in the follicle-stimulating hormone (FSH) receptor (FSHR)
      gene are rarely detected due to the absence of a clearly defined phenotype,
      particularly in men. We here report the biochemical features of a novel mutation
      in the first extracellular loop of the FSHR. The mutation (N431I) was detected in
      an asymptomatic man exhibiting normal spermatogenesis, suppressed serum FSH, and
      normal or elevated levels of biochemical markers of FSH action. Employing
      different experimental strategies on HEK-293 cells transiently expressing the
      N431I FSHR mutant, we found that the mutation led to decreased cell surface
      plasma membrane expression of the receptor protein, but conferred a low level of
      constitutive activity associated with markedly altered agonist-stimulated
      desensitization and internalization. These latter features may contribute and/or
      amplify the persistent activation of the receptor in both absence and presence of
      agonist and provide new insights into opportunities for adjuvant therapies based
      on disruption of these processes.

PMID- 22954681
TI  - Experimental and computational study of inter- and intra- species specificity of
      gonadotropins for various gonadotropin receptors.
AB  - The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      and their receptors play critical roles in vertebrate reproduction. In order to
      study intra- and interspecies ligand promiscuity of gonadotropins, COS-7 cells
      were transiently transfected with one of the gonadotropin receptor genes, FSHR or
      LHR, and tested for activation by gonadotropins from representative fish orders:
      Aquilliformes (eel; e), Salmoniformes (trout; tr), and Perciformes (tilapia; ta),
      and of mammalian origin: porcine (p), bovine (b) and human (h). The study reveals
      complex relations between the gonadotropin hormones and their receptors. Each
      gonadotropin activated its own cognate receptor. However, taLHR was also
      activated by hCG and eLHR was activated by hFSH, hCG, and trFSH. For FSHR, the
      only cross-reactivity detected was for hFSHR, which was activated by pFSH and
      bFSH. These findings are of great interest and applicability in the context of
      activation of various GTHRs by their ligands and by ligands from other
      vertebrates. Analysis of the three-dimensional models of the structures
      highlights the importance of residues outside of the currently established
      hormone-receptor interface region. In addition, the interface residues in taFSHR
      and the effect of exon duplication, which causes an insert in the LRR domain, are
      suggested to affect the interaction and binding of taFSH.

PMID- 22954683
TI  - Patent controversies and court cases: cancer diagnosis, therapy and prevention.
AB  - Patents are issued essentially by all countries on inventions that are deemed
      novel, non-obvious, clearly described and of significant utility or industrial
      application. The only exceptions to patenting an invention are abstract ideas,
      laws of nature and natural phenomena, although the exceptions vary depending on
      countries where moral, public order or human rights considerations are also taken
      into account. Although patent laws are updated over decades, the rapid progress
      of science creates situations that the patent laws on the book cannot address,
      leading to contentious legal issues. This is often true for life saving drugs,
      particularly drugs for cancers or HIV/AIDS, which are expensive and beyond the
      reach of poor people because of the proprietary positions of these patented
      drugs. Another contentious issue is the patent eligibility of human genes and
      mutations that are often thought of nature's contribution to human health and
      propagation and should be beyond the reach of patentability. In this review, we
      address some of these current legal issues and their implications for the
      development of diagnostic methods, therapeutic interventions and even prevention
      for cancer, a scourge of mankind.

PMID- 22954684
TI  - A second target of benzamide riboside: dihydrofolate reductase.
AB  - Dihydrofolate reductase (DHFR) is an essential enzyme involved in de novo purine
      and thymidine biosynthesis. For several decades, selective inhibition of DHFR has
      proven to be a potent therapeutic approach in the treatment of various cancers
      including acute lymphoblastic leukemia, non-Hodgkin's lymphoma, osteogenic
      sarcoma, carcinoma of the breast, and head and neck cancer. Therapeutic success
      with DHFR inhibitor methotrexate (MTX) has been compromised in the clinic, which
      limits the success of MTX treatment by both acquired and intrinsic resistance
      mechanisms. We report that benzamide riboside (BR), via anabolism to benzamide
      adenine dinucleotide (BAD) known to potently inhibit inosine monophosphate
      dehydrogenase (IMPDH), also inhibits cell growth through a mechanism involving
      downregulation of DHFR protein. Evidence to support this second site of action of
      BR includes the finding that CCRF-CEM/R human T-cell lymphoblasic leukemia cells,
      resistant to MTX as a consequence of gene amplification and overexpression of
      DHFR, are more resistant to BR than are parental cells. Studies of the mechanism
      by which BR lowers DHFR showed that BR, through its metabolite BAD, reduced NADP
      and NADPH cellular levels by inhibiting nicotinamide adenine dinucleotide kinase
      (NADK). As consequence of the lack of NADPH, DHFR was shown to be destabilized.
      We suggest that, inhibition of NADK is a new approach to downregulate DHFR and to
      inhibit cell growth.

PMID- 22954685
TI  - A new bioactive Schiff base ligands derived from propylazo-N-pyrimidin-2-yl
      benzenesulfonamides Mn(II) and Cu(II) complexes: synthesis, thermal and
      spectroscopic characterization biological studies and 3D modeling structures.
AB  - New series of Schiff base ligand H(2)L and their Cu(II) and Mn(II) complexes
      derived from azosulfapyrimidine were synthesized and characterized by elemental
      and thermal studies conductance measurements IR, electronic and EPR spectra. 3D
      modeling of the ligand indicate that azo group does not participate in complex
      formation and surface potential on one of the ligand under study indicate that
      electron density around azomethine groups are much higher than the azo group
      therefore coordination takes place around azomethine groups. The variety in the
      geometrical structures depends on the nature of both the metal ions and the
      Schiff base ligands. The thermo kinetic parameters are calculated and discussed.
      The biological activities of the ligands and complexes have been screened in
      vitro against some bacteria and fungi to study their capacity to inhibit their
      growth and to study the toxicity of the compounds.

PMID- 22954686
TI  - Ultrasonic emulsification of food-grade nanoemulsion formulation and evaluation
      of its bactericidal activity.
AB  - Basil oil (Ocimum basilicum) nanoemulsion was formulated using non-ionic
      surfactant Tween80 and water by ultrasonic emulsification method. Process of
      nanoemulsion development was optimized for parameters such as surfactant
      concentration and emulsification time to achieve minimum droplet diameter with
      high physical stability. Surfactant concentration was found to have a negative
      correlation with droplet diameter, whereas emulsification time had a positive
      correlation with droplet diameter and also with intrinsic stability of the
      emulsion. Stable basil oil nanoemulsion with droplet diameter 29.3 nm was
      formulated by ultrasonic emulsification for 15 min. Formulated nanoemulsion was
      evaluated for antibacterial activity against Escherichia coli by kinetics of
      killing experiment. Fluorescence microscopy and FT-IR results showed that
      nanoemulsion treatment resulted alteration in permeability and surface features
      of bacterial cell membrane.

PMID- 22954687
TI  - Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged >=7
      years.
AB  - BACKGROUND: The Asian population, in general, has higher antiretroviral
      concentrations than those who are not Asian, but there are limited
      pharmacokinetic data for darunavir/ritonavir in Asian children. METHODS: Thai
      children aged >=7 years and with body weight (BW)>=20 kg who were on
      darunavir/ritonavir for >=2 weeks underwent 12-h pharmacokinetics with blood
      sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing.
      Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to <30 kg, n=12),
      450/100 mg twice daily (BW 30 to <40 kg, n=2) or 600/100 mg twice daily (BW >=40
      kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution.
      RESULTS: Of the 19 children, 8 were female, median age was 13 years (range 7-16)
      and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment
      was 11 months. The geometric mean values for darunavir were 60.3 h*mg/l for the
      area under the concentration-time curve at 0-12 h (AUC(0-12)), 8.3 mg/l for the
      maximum concentration (C(max)) and 3.1 for the concentration prior to the next
      dose (C(12)) with no differences between dosing groups. All had C(12) above the
      protein binding adjusted 50% effective concentration (EC(50)) of protease
      inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters
      were similar to those in non-Asian individuals from the DELPHI study, in which 13
      of 20 with BW<40 kg used 50 or 60 mg ritonavir boosting. CONCLUSIONS: Thai
      children aged >=7 years who were on standard darunavir dosing with 100 mg
      ritonavir boosting had adequate and comparable darunavir AUC(0-12), C(max) and
      C(12) to non-Asian children who mainly used lower doses of ritonavir boosting. A
      ritonavir boosting dose of 100 mg can be used for children weighing >=20 kg,
      particularly when lower dose formulations are unavailable or if intolerant to the
      solution.

PMID- 22954688
TI  - cAMP-dependent protein kinase is essential for hypoxia-mediated epithelial
      mesenchymal transition, migration, and invasion in lung cancer cells.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Hypoxia is
      known to increase cancer cell migration and invasion. We have previously reported
      that hypoxia induces epithelial-mesenchymal transition (EMT) in lung cancer
      cells. However, it is unknown whether hypoxia promotes lung cancer cell migration
      and invasion via EMT and whether cyclic AMP (cAMP) dependent protein kinase (PKA)
      plays a role in this process. We found that hypoxia increased PKA activity and
      induced mRNA and protein expression of PKA catalytic subunit alpha (PKACA), and
      regulatory subunits R1A and R1B. Knockdown of HIF-1/2alpha prevented hypoxia
      mediated induction of PKACA mRNA expression and PKA activity. Inhibition of PKA
      activity with chemical inhibitors prevented EMT induced by hypoxia and tumor
      growth factor beta1. However, activation of PKA by forskolin and 8-Br-cAMP did
      not induce EMT. Furthermore, treatment with H89 and knockdown of PKACA prevented
      hypoxia-mediated, EMT, cell migration, and invasion, whereas overexpression of
      mouse PKACA rescued hypoxia-mediated migration and invasion in PKACA deficient
      cancer cells. Our results suggest that hypoxia enhances PKA activity by
      upregulating PKA gene expression in a HIF dependent mechanism and that PKA plays
      a key role in hypoxia-mediated EMT, migration, and invasion in lung cancer cells.

PMID- 22954689
TI  - Gastroduodenal mucosal defense.
AB  - PURPOSE OF REVIEW: To review recent developments in the field of gastroduodenal
      mucosal defense. RECENT FINDINGS: Research in the field of gastroduodenal mucosal
      defense is shifting from animal models of mucosal injury towards the elucidation
      of molecular mechanisms that protect the mucosa at the cellular level.
      Accordingly, the recent literature is focused on endogenous antioxidants such as
      mitochondrial superoxide dismutase (SOD), and heme oxygenase-1, mucosal receptors
      such as the Toll-like receptors and protease-activated receptors, endogenous
      proteins with protective effects such as the matrix metalloproteinases, heat
      inducible factors and trefoil factors, protective functions of submucosal
      mononuclear cells, junctional proteins affecting mucosal permeability, and
      hormone-mediated protective mechanisms mediated by estrogens, vasoactive
      peptides, and other hormones. SUMMARY: These new published findings contribute to
      our overall understanding of gastroduodenal defense and suggest innovative
      avenues of future research and possible novel therapeutic targets.

PMID- 22954690
TI  - Prevention of catheter-related blood stream infections in children with
      intestinal failure.
AB  - PURPOSE OF REVIEW: Catheter-related bloodstream infections (CRBSIs) account for a
      major source of morbidity in children with intestinal failure. Many of these
      patients require long-term central venous access, placing them at significant
      risk for these infections. The purpose of this review is to highlight the most
      current strategies and interventions for minimizing CRBSIs in this population.
      RECENT FINDINGS: Strategies for the prevention of CRBSIs continue to evolve,
      although most have not been specifically evaluated in children with intestinal
      failure. Some of the more recent interventions that are likely to be effective in
      this population include creating standardized protocols for catheter insertion
      and maintenance, ethanol lock therapy, and occasional use of antimicrobial
      catheters and dressings. SUMMARY: Every effort must be made to prevent CRBSIs in
      infants and children with intestinal failure. Disease specific risk factors must
      be considered when determining the best approach for infection prevention.
      Because of their long-term access needs, checklists and protocols to maintain
      strict sterile technique at the time of catheter insertion are useful.
      Additionally, these children often have some degree of intestinal bacterial
      overgrowth secondary to dilation and dysmotility. Therefore, the use of
      antimicrobial locks, catheters and dressings likely provide benefit for some
      patients.

PMID- 22954691
TI  - Early gastric cancer:  an update on endoscopic management.
AB  - PURPOSE OF REVIEW: The review focuses on the latest endoscopic techniques that
      are emerging in the management of early gastric cancer. RECENT FINDINGS: Improved
      sensitivity and specificity in the diagnosis of early gastric cancers has been
      demonstrated in a number of studies by narrow band imaging (92.7 and 94.5%),
      confocal laser endomicroscopy (90.2 and 98.5%), and magnification chromoendoscopy
      (88.6 and 93.2%), respectively. In early gastric cancer, endoscopic submucosal
      dissection (ESD) has been shown to be superior to endoscopic mucosal resection
      (EMR) with curative resection rate at 79.5% for ESD vs. 59% for EMR, and a lower
      local recurrence rate at 0.82% for ESD vs. 5.03% for EMR. SUMMARY: Advanced
      diagnostic and therapeutic endoscopic techniques are changing the paradigm of
      care in patients with early gastric cancers.

PMID- 22954692
TI  - Gastric secretion.
AB  - PURPOSE OF REVIEW: This review summarizes the past year's literature regarding
      the regulation of gastric exocrine and endocrine secretion, both basic science
      and clinical. RECENT FINDINGS: Gastric acid secretion facilitates the digestion
      of protein as well as the absorption of iron, calcium, vitamin B12, and certain
      medications as well as prevents bacterial overgrowth, enteric infection, and
      possibly community-acquired pneumonia, spontaneous bacterial peritonitis, and IgE
      mediated food allergy. It is regulated by neural (e.g., pituitary adenylate
      cyclase-activating peptide), hormonal (e.g., gastrin, ghrelin, and apelin), and
      paracrine (e.g., histamine) pathways as well as by chemical (e.g., amino acids)
      and bacterial stimuli (e.g., Helicobacter pylori). Novel peptides, which may
      possess physiologic function, have been identified in gastric mucosal
      neuroendocrine cells including parathyroid hormone-like hormone in histamine
      secreting enterochromaffin-like cells and hepcidin in acid-secreting parietal
      cells. The secretion of hydrochloric acid by parietal cells involves
      translocation of the proton pump, HK-ATPase, to the apical membrane along with
      activation of apical chloride and potassium channels. Serum markers include
      chromogranin A for neuroendocrine tumors, pepsinogen I for gastric atrophy, and
      pepsinogen II for H. pylori infection. SUMMARY: We continue to make progress in
      our understanding of the regulation of gastric acid secretion in health and
      disease.

PMID- 22954693
TI  - Stomach and duodenum.

PMID- 22954695
TI  - Loss of OATP1B3 function causes Rotor syndrome: implications for potential use of
      inhibitors in cancer.
AB  - There has been increasing recognition that organic anion transporter proteins
      (OATPs) play an important role in the biology of various cancers. De novo
      expression of OATPs has been identified in breast, colon, pancreatic, gastric and
      prostate cancer cells, among others. In patients with prostate cancer,
      polymorphisms encoding decreased functioning OATP1B3 were associated with a
      longer time to progression on androgen deprivation therapy and a longer overall
      survival which is likely caused by reduced tumoral testosterone uptake. Because
      of these findings, therapeutic inhibition targeting OATP1B3 has been proposed.
      However, any enthusiasm for inhibiting OATP1Bs therapeutically has been tempered
      by reservations about potential consequences. For instance, inhibitors could
      interfere with several normal physiological processes mediated by OATP1B3 (i.e.,
      bile acid reuptake, bilirubin uptake, etc) or cause potential, as-yet unknown,
      drug interactions by barring hepatic uptake, subsequent metabolism and
      elimination.

PMID- 22954694
TI  - The human proton-coupled folate transporter: Biology and therapeutic applications
      to cancer.
AB  - This review summarizes the biology of the proton-coupled folate transporter
      (PCFT). PCFT was identified in 2006 as the primary transporter for intestinal
      absorption of dietary folates, as mutations in PCFT are causal in hereditary
      folate malabsorption (HFM) syndrome. Since 2006, there have been major advances
      in understanding the mechanistic roles of critical amino acids and/or domains in
      the PCFT protein, many of which were identified as mutated in HFM patients, and
      in characterizing transcriptional control of the human PCFT gene. With the
      recognition that PCFT is abundantly expressed in human tumors and is active at
      pHs characterizing the tumor microenvironment, attention turned to exploiting
      PCFT for delivering novel cytotoxic antifolates for solid tumors. The finding
      that pemetrexed is an excellent PCFT substrate explains its demonstrated clinical
      efficacy for mesothelioma and non-small cell lung cancer, and prompted
      development of more PCFT-selective tumor-targeted 6-substituted pyrrolo[2,3
      d]pyrimidine antifolates that derive their cytotoxic effects by targeting de novo
      purine nucleotide biosynthesis.

PMID- 22954696
TI  - Repeated cisplatin treatment can lead to a multiresistant tumor cell population
      with stem cell features and sensitivity to 3-bromopyruvate.
AB  - Cisplatin is used in treatment of several types of cancer, including epithelial
      ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate
      longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were
      repeatedly treated with low doses. In the SKOV-3 cell line originating from
      malignant ascites, but not in A2780 cells from a primary tumor, this led to
      emergence of a stable population (SKOV-3-R) which in the absence of cisplatin
      showed increased motility, epithelial-mesenchymal transition (EMT) and expression
      of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed
      self-renewing spheres in serum-free stem cell medium. Despite upregulation of
      mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3
      R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor
      initiating cells (TICs) are highly chemoresistant and are believed to cause
      relapse into disseminated and resistant EOC. Our second aim was therefore to
      target resistance in these TIC-like cells. Resistance could be correlated with
      upregulation of hexokinase-II and VDAC, which are known to form a survival
      promoting mitochondrial complex. The cells were thus sensitive to 3
      bromopyruvate, which dissociates hexokinase-II from this complex, and were
      particularly sensitive to combination treatment with cisplatin at doses down to
      0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially
      aggressive TIC populations.

PMID- 22954697
TI  - Salvage radiotherapy for prostate cancer: Finding a way forward using
      radiobiological modeling.
AB  - PURPOSE: Recent modeling efforts, based on reported outcomes following salvage
      radiotherapy (SRT) for prostate cancer, predict the likelihood of biochemical
      control (tumor control probability, TCP) as a function of pre-treatment prostate
      specific antigen (PSA) and SRT dose. Similar instruments predict the risk of
      grade >= 3 late toxicity (normal tissue complication probability, NTCP) as a
      function of SRT dose. Here we explore how changes in the parameters of those
      models might affect the optimal SRT dose and clinical outcomes. MATERIALS AND
      METHODS: Baseline TCP and NTCP model parameters were established in a previous
      report. Pre-treatment PSA was set at 0.4 ng/mL. Model parameters were modified to
      explore four scenarios: (1) improving the safety of SRT, (2) increasing tumor
      cell radiosensitivity, (3) increasing the cure rate achievable with SRT and (4)
      adoption of hypofractionated SRT schedules. The "optimal" SRT dose, defined as
      the dose that maximized the likelihood of achieving biochemical control without
      causing late toxicity, was identified for each scenario. RESULTS: Improving the
      safety of SRT increased the optimal SRT dose, while radiosensitization decreased
      the optimal dose. Both changes were predicted to increase the probability of
      biochemical control and decrease late toxicity rates. Increasing the cure rate
      achievable with SRT (eg: improving patient selection or combining SRT with
      effective systemic therapy) provided the greatest gains in TCP. Adoption of a
      hypofractionated SRT schedule was predicted to improve both biochemical control
      and late toxicity. CONCLUSIONS: Modeling exercises demonstrate the significant
      gains that may be achieved with improved implementation of SRT for prostate
      cancer. Strategies to realize the effects modeled in this report should be
      explored in clinical trials.

PMID- 22954698
TI  - A pilot study of paclitaxel combined with gemcitabine followed by interleukin-2
      and granulocyte macrophage colony-stimulating factor for patients with metastatic
      melanoma.
AB  - It has been suggested that paclitaxel and gemcitabine modulate the immune system.
      This paper reports the safety and efficacy of paclitaxel plus gemcitabine
      followed by interleukin-2 (IL-2)and granulocyte macrophage colony-stimulating
      factor (GM-CSF), the PGIG chemobiotherapy, for patients with metastatic melanoma.
      All patients received 175 mg/m ( 2)  paclitaxel on day 1 and 800 mg/m ( 2) 
      gemcitabine on day two. IL-2 and GM-CSF were administered from day 4 to day 8 at
      a dosage of 2 MIU/m ( 2)  and 100 MUg, respectively. The PGIG chemobiotherapy was
      repeated every 21 d. Serum cytokine levels at baseline and at the end of the
      second cycle were measured via flow cytometry. Twenty-seven patients with
      metastatic melanoma accepted PGIG chemobiotherapy from August 2009 to March 2011.
      There were five patients that exhibited a partial response, 14 patients that
      exhibited a stable response and eight that displayed progressive disease.
      Therefore, the response rate was 18.5%, and the disease control rate was 70.4%.
      The median time to progression and median survival were 4 mo and 8 mo,
      respectively. The one-year and two-year survival rates were 25.9% and 18.5%,
      respectively. Frequent side effects included chills, fever, arthralgia, rash and
      pruritus. Among the 13 patients who experienced a rash and pruritus and the 14
      patients who did not suffer from this side effect, the response rates and disease
      control rates were 30.8% vs 7.1% and 77% vs 64.2%, respectively. No relationship
      between serum IL-6 levels, clinical response, and either skin side effect was
      observed. The PGIG chemobiotherapy is safe and effective for the treatment of
      patients with advanced melanoma, but randomized trials are necessary to validate
      this effect.

PMID- 22954699
TI  - Prognostic value of aberrant hypermethylation in pleural effusion of lung
      adenocarcinoma.
AB  - Lung adenocarcinoma is one of the most frequent causes of malignant pleural
      effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic
      changes are commonly related to human neoplasia, scarce date is available on
      patients with MPE. We aimed to estimate the prognostic value of DNA methylation
      of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to
      lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR
      was used to study the methylation status of the promoter region of tumor
      suppressor genes p16/INK4a, MGMT, BRCA1 and RARbeta in pleural fluid. Clinical
      data and survival were collected. Survival analysis was performed using Kaplan
      Meier plots and Cox regression. Hypermethylation in at least one gene was
      detected in 25 patients (83.3%). On multivariate analysis factors significantly
      associated with shorter survival were the lack of hypermethylation in any of the
      studied genes (hazard ratio = 9.3; p = 0.001), Charlson index >= 3 (hazard ratio
      = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001).
      Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be
      useful in predicting prognosis, but further studies are needed to validate our
      findings.

PMID- 22954700
TI  - Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo.
AB  - Cancer cells convert glucose preferentially to lactate even in the presence of
      oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim
      at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to
      acetylCoA thus preventing lactate formation. Therefore, the aim of this study was
      to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells.
      We investigated the effects of (R)-(+)-alpha-lipoic acid (LPA) and
      dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on
      suppression of aerobic glycolysis and induction of cell death. The neuroblastoma
      cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3 were
      incubated with different concentrations (0.1-30 mM) of LPA and DCA. The effects
      of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG
      uptake, lactate production and induction of apoptosis (flow cytometric detection
      of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been
      inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p,
      18.5 mg/kg) starting at day 7 p.i.. Tumor development was measured with a sliding
      caliper and monitored via [18F]-FDG-PET. Residual tumors after therapy were
      examined histopathologically. These data suggests that LPA can reduce (1) cell
      viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and
      increase apoptosis in all investigated cell lines. In contrast, DCA was almost
      ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment
      with LPA retarded tumor progression. Therefore, LPA seems to be a promising
      compound for cancer treatment.

PMID- 22954701
TI  - EGFR tyrosine kinase inhibition induces autophagy in cancer cells.
AB  - The epidermal growth factor receptor (EGFR) signaling pathway is frequently
      dysregulated in a variety of human malignancies. As a result, agents have been
      developed to selectively inhibit the tyrosine kinase function of EGFR (EGFR-TKI)
      for cancer therapy. However, the clinical efficacy of these drugs to date has
      been limited by both acquired and intrinsic resistance. Macroautophagy, a process
      of intracellular proteolysis, has been shown to be activated in response to EGFR
      targeted therapy. However, the specific role of the induction of autophagy
      remains controversial. Here we show that autophagy is induced in a dose-dependent
      manner by in vitro treatment of multiple cancer cell lines with EGFR-TKI.
      Additionally, we find that in cells highly resistant to EGFR-TKI, autophagy is
      not robustly activated and that co-treatment of these cells with rapamycin, a
      known inducer of autophagy, can partially restore sensitivity to EGFR-TKI.
      Finally, we demonstrate that, in resistant cell lines, EGFR-TKI sensitivity can
      be further inhibited by siRNA-mediated depletion of the critical autophagy
      protein ATG7. Thus, our data suggests that defective autophagy may be an EGFR-TKI
      resistance mechanism and that activation of autophagy may be a viable strategy to
      augment the cytotoxic effect of EGFR-TKIs.

PMID- 22954702
TI  - Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles
      and its inhibition of hepatocellular carcinoma in mice.
AB  - Biodegradable polymer nanoparticle drug delivery systems are characterized by
      targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced
      drug stability and lowered side effects; these drug delivery systems are widely
      used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5
      fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer
      known to have the advantages described above, and 5-FU. The GC/5-FU nanoparticle
      is a sustained release system, it was showed that the peak time, half-life time,
      mean residence time (MRT) and area of under curve (AUC) of GC/5-FU were longer or
      more than those of the 5-FU group, but the maximum concentration (Cmax) was
      lower. The distribution of GC/5-FU in vivo revealed the greatest accumulation in
      the hepatic cancer tissues, and the hepatic cell was the target of the
      nanoparticles. Toxicology research showed that the toxicity of GC-5-FU was lower
      than that of 5-FU in mice. In vivo experiments showed that GC/5-FU can
      significantly inhibit tumor growth in an orthotropic liver cancer mouse model.
      GC/5-FU treatment can significantly lower the tumor weight and increase the
      survival time of mice when compared with 5-FU treatment alone. Flow cytometry and
      the TUNEL assay revealed that compared with 5-FU, GC/5-FU caused higher rates of
      G 0-G 1 arrest and apoptosis in hepatic cancer cells.

PMID- 22954703
TI  - Characterization of the conversion between CD133+ and CD133- cells in colon
      cancer SW620 cell line.
AB  - The state of cancer stem cells (CSC) under reversible fluctuations, which has
      been revealed in breast cancer cells most recently, suggests that subpopulations
      with distinct phenotypes and functions within cancer cells can undergo inter
      conversion. To investigate the possibility in colon cancer cells, we employed
      CD133 as the CSC marker, and characterized CD133 expression pattern and the
      biological features of the CD133 (+)  and CD133 (-)  subsets. Flow cytometry
      revealed that CD133 was bimodally expressed in SW620 cells among eight colon
      cancer cell lines. The CD133 (+)  clonal SW620 cells displayed a differential
      gene expression profile, higher cellular reactive oxygen species (ROS), enhanced
      tumorigenesis and resistance to 5-fluorouracil. The conversion in term of the
      CD133 phenotype of the sorted cells was observed in vitro and in vivo. The
      fraction of the CD133 (+)  cells decreased from 99% to 80% in the sorted CD133
      (+)  population while rising from 5 to 10% in the sorted CD133 (-)  population
      during the first 20-day cultivation and then stayed almost unchanged. A fraction
      (about 20%) of the CD133 (+)  clonal cells lost their CD133 marker while about
      10% of the CD133 (-)  clonal cells acquired the CD133 marker. 5-Azacytidine
      enhanced the fraction of the CD133 (+)  cells in both of the CD133 (+)  and CD133
      (-)  clonal cells. Our data demonstrate that CD133 expression is dynamic and
      reversible, and reveal the inter-conversion between the CD133 (+)  and the CD133
      (-)  SW620 cells, suggesting that the CD133 phenotype of SW620 cell population is
      retained by the conversion between the two cell subsets.

PMID- 22954704
TI  - Falls and cognitive dysfunction impair health-related quality of life in patients
      with cirrhosis.
AB  - INTRODUCTION: Falls are frequent in patients with cirrhosis and cognitive
      dysfunction and can deteriorate health-related quality of life (HRQoL).
      OBJECTIVE: To evaluate the relationship between previous falls and HRQoL in
      patients with cirrhosis. METHODS: We measured HRQoL in 118 outpatients with
      cirrhosis using the Medical Outcomes Study Short Form (SF-36) questionnaire,
      grouping items into the Physical Component Score (PCS) and the Mental Component
      Score (MCS). The incidence of accidental falls in the 12 months before the study
      was assessed using a specific questionnaire. The Psychometric Hepatic
      Encephalopathy Score (PHES) was administered to assess cognitive dysfunction. We
      considered cognitive dysfunction if PHES was less than -4. HRQoL was compared
      between patients with falls and patients without falls. RESULTS: HRQoL was lower
      in patients with previous falls than in patients without falls (P<0.05 in all
      domains of SF-36). In the multivariate analysis, the only independent factors
      that affected the HRQoL in the PCS were (B coefficient, 95% confidence interval)
      cognitive dysfunction (6.5, 3.2-9.7, P<0.001), previous variceal bleeding (3.9,
      0.4-7.3, P=0.02), anemia (3.2, 0.07-6.4, P=0.049), and hyponatremia (9.3, 1.07
      17.5, P<0.02). Multivariate analysis for MCS showed the independent factors for
      worse HRQoL were female sex (12.2, 6.9-17.5, P<0.001) and previous falls (10.3,
      4.0-16.5, P=0.001). CONCLUSION: Falls and cognitive dysfunction are independent
      factors associated with impaired HRQoL in patients with cirrhosis. Strategies
      addressed to improve HRQoL in these patients should consider the treatment of
      cognitive dysfunction and prevention of falls.

PMID- 22954706
TI  - Imaging and treatment response after ischaemic stroke.

PMID- 22954705
TI  - MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a
      prospective cohort study.
AB  - BACKGROUND: Whether endovascular stroke treatment improves clinical outcomes is
      unclear because of the paucity of data from randomised placebo-controlled trials.
      We aimed to establish whether MRI can be used to identify patients who are most
      likely to benefit from endovascular reperfusion. METHODS: In this prospective
      cohort study we consecutively enrolled patients scheduled to have endovascular
      treatment within 12 h of onset of stroke at eight centres in the USA and one in
      Austria. Aided by an automated image analysis computer program, investigators
      interpreted a baseline MRI scan taken before treatment to establish whether the
      patient had an MRI profile (target mismatch) that suggested salvageable tissue
      was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h
      of the revascularisation procedure) and defined as a more than 50% reduction in
      the volume of the lesion from baseline on perfusion-weighted MRI. The primary
      outcome was favourable clinical response, defined as an improvement of 8 or more
      on the National Institutes of Health Stroke Scale between baseline and day 30 or
      a score of 0-1 at day 30. The secondary clinical endpoint was good functional
      outcome, defined as a modified Rankin scale score of 2 or less at day 90.
      Analyses were adjusted for imbalances in baseline predictors of outcome.
      Investigators assessing outcomes were masked to baseline data. FINDINGS: 138
      patients were enrolled. 110 patients had catheter angiography and of these 104
      had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%)
      patients with target mismatch and 12 of 21 (57%) patients without target mismatch
      had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for
      favourable clinical response associated with reperfusion was 8.8 (95% CI 2.7
      29.0) in the target mismatch group and 0.2 (0.0-1.6) in the no target mismatch
      group (p=0.003 for difference between ORs). Reperfusion was associated with
      increased good functional outcome at 90 days (OR 4.0, 95% CI 1.3-12.2) in the
      target mismatch group, but not in the no target mismatch group (1.9, 0.2-18.7).
      INTERPRETATION: Target mismatch patients who had early reperfusion after
      endovascular stroke treatment had more favourable clinical outcomes. No
      association between reperfusion and favourable outcomes was present in patients
      without target mismatch. Our data suggest that a randomised controlled trial of
      endovascular treatment for patients with the target mismatch profile is
      warranted. FUNDING: National Institute for Neurological Disorders and Stroke.

PMID- 22954707
TI  - Cell recycle batch fermentation of high-solid lignocellulose using a recombinant
      cellulase-displaying yeast strain for high yield ethanol production in
      consolidated bioprocessing.
AB  - The aim of this study is to develop a scheme of cell recycle batch fermentation
      (CRBF) of high-solid lignocellulosic materials. Two-phase separation consisting
      of rough removal of lignocellulosic residues by low-speed centrifugation and
      solid-liquid separation enabled effective collection of Saccharomyces cerevisiae
      cells with decreased lignin and ash. Five consecutive batch fermentation of 200
      g/L rice straw hydrothermally pretreated led to an average ethanol titer of 34.5
      g/L. Moreover, the display of cellulases on the recombinant yeast cell surface
      increased ethanol titer to 42.2 g/L. After, five-cycle fermentation, only 3.3 g/L
      sugar was retained in the fermentation medium, because cellulase displayed on the
      cell surface hydrolyzed cellulose that was not hydrolyzed by commercial
      cellulases or free secreted cellulases. Fermentation ability of the recombinant
      strain was successfully kept during a five-cycle repeated batch fermentation with
      86.3% of theoretical yield based on starting biomass.

PMID- 22954708
TI  - Identification of novel markers of alternative activation and potential
      endogenous PPARgamma ligand production mechanisms in human IL-4 stimulated
      differentiating macrophages.
AB  - We analyzed global gene expression profiles of IL-4 induced alternatively
      activated as well as IFNgamma+TNFalpha stimulated classically activated human
      monocyte derived macrophages and identified novel IL-4 regulated alternative
      activation marker genes including MS4A4A, SLA, CD180, and ENPP2. Transcription
      factor prediction analysis of IL-4 regulated genes suggested that the regulated
      genes are involved in a complex regulation of lipid metabolism, defense against
      cell metabolism derived reactive oxygen species, and basal expression of
      inflammation linked genes. Both an in silico transcription activation prediction
      as well as experimental data suggested the presence of alternative macrophage
      activation specific endogenous PPARgamma ligand producing mechanisms. We found
      the induction of three enzymes whose activity can potentially generate endogenous
      PPARgamma ligands in an IL-4 dependent manner. These are MAOA, ENPP2, and ALOX15
      producing 5-methoxy-indole acetate, lysophosphatidic acid (LPA) and 13
      hydroxyoctadienoic acid (13-HODE), and/or 15-hydroxyeicosatetraenoic acid (15
      HETE), respectively. Our data suggest that global gene expression profiling,
      combined with computational transcription activity prediction, can lead to
      identification of transcriptional networks that underpin cellular subtype
      specification.

PMID- 22954710
TI  - B16 melanoma cells increase B-1 cell survival, IL-10 production and
      radioresistance in vitro.
AB  - B-1 cells can be differentiated from B-2 cells because they are predominantly
      located in the peritoneal and pleural cavities and have distinct phenotypic
      patterns and activation properties. The role of both cell populations in cancer
      progression is still controversial. Previous studies have indicated that direct
      contact between B-1 cells and B16 melanoma tumor cells (B16) increases the
      metastatic potential of the tumor cells. However, cellular changes that are
      induced in B-1 cells during the interaction between these two cell types have not
      been evaluated. In the present study, it is hypothesized that B-1 cells are
      modified after their interaction with tumor cells, leading to both increased cell
      viability and rate of proliferation. Additionally, soluble factors that were
      secreted by B16 cells were sufficient to augment B-1 cell viability and to modify
      the production of IL-10 by B-1 cells. Impressively, after direct or indirect
      contact with the B16 cells, B-1 cells became resistant to radiation-induced cell
      death. Thus, future studies that assess the importance of concomitant immunity
      and other conventional therapies in cancer treatment are needed.

PMID- 22954709
TI  - Natural killer T cells are required for lipopolysaccharide-mediated enhancement
      of atherosclerosis in apolipoprotein E-deficient mice.
AB  - Lipopolysaccharide (LPS) has been shown to accelerate atherosclerosis and to
      increase the prevalence of IL-4-producing natural killer T (NKT) cells in various
      tissues. However, the role of NKT cells in the development of LPS-induced
      atherosclerotic lesions has not been fully tested in NKT cell-deficient mice.
      Here, we examined the lesion development in apolipoprotein E knockout (apoE-KO)
      mice and apoE-KO mice on an NKT cell-deficient, CD1d knockout (CD1d-KO)
      background (apoE-CD1d double knockout; DKO). LPS (0.5 MUg/g body weight/wk) or
      phosphate-buffered saline (PBS) was intraperitoneally administered to apoE-KO and
      DKO mice (8-wk old) for 5 wk and atherosclerotic lesion areas were quantified
      thereafter. Consistent with prior reports, NKT cell-deficient DKO mice showed
      milder atherosclerotic lesions than apoE-KO mice. Notably, LPS administration
      significantly increased the lesion size in apoE-KO, but not in DKO mice, compared
      to PBS controls. Our findings suggest that LPS, and possibly LPS-producing
      bacteria, aggravate the development of atherosclerosis primarily through NKT cell
      activation and subsequent collaboration with NK cells.

PMID- 22954713
TI  - Finite element analysis of a micromechanical model of bone and a new 3D approach
      to validation.
AB  - Finite Element Analysis (FEA) is now widely used to analyse the mechanical
      behaviour of bone structures. Ideally, simulations are validated against
      experimental data. To date, validation of Finite Element Models (FEMs) has been 2
      Dimensional (2D) only, being based on comparison with surface-mounted strain
      gauge readings. In this study we present a novel 3-Dimensional (3D) approach to
      validation that allows comparison of modelled with experimental results between
      any two points in 3D space throughout the structure, providing magnitude and
      direction data for comparison, internally and externally. Specifically, we
      validate a FEM of a rat tibia, including trabecular network geometry, using a
      material testing stage housed within a microCT scanner. We further apply novel
      landmark based morphometric approaches to more effectively compare modelled and
      experimental results. 542 landmark points on the cortical and trabecular bone
      surfaces of the model were selected and validated in 3D against experimental
      data. This approach may hold considerable potential in fields wherein a better
      understanding of the mechanical behaviour of trabecular networks is important,
      e.g., the studies of osteoporosis and trabecular loss after orthopaedic implant
      insertion.

PMID- 22954711
TI  - The role of IL-2 in the activation and expansion of regulatory T-cells and the
      development of experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is an autoimmune disease that affects ~ 400,000 people in
      the US. It is a chronic, disabling disease with no cure, and the current
      treatment includes use of immunosuppressive drugs that often exhibit toxic side
      effects. Thus, there is a pressing need for alternate and more effective
      treatment strategies that target the components of inflammatory cells. In recent
      years, regulatory T-cells (Tregs) have been found to play an important role in
      preventing the development of autoimmunity. Thus, expansion of Tregs in vivo has
      the therapeutic potential against autoimmune diseases. Because Tregs
      constitutively express IL-2 receptors (IL-2Rs), we tested the effect of
      administration of IL-2 on the development of experimental autoimmune
      encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). We used IL-2
      both before (pre-treatment) or after (post-treatment) immunization with myelin
      oligodendrocyte glycoprotein (MOG35-55) peptide to induce EAE. The data
      demonstrated that pre-treatment with a moderate dose of IL-2 caused significant
      amelioration of EAE. Tissue histopathology of the central nervous system also
      confirmed the effectiveness of IL-2 pre-treatment by decreasing cellular
      infiltration in the spinal cord and preserving tissue integrity. IL-2
      pretreatment expanded Treg cells while preventing the induction of Th17 during
      EAE development. In contrast, post-treatment with IL-2 failed to suppress EAE
      despite induction of Tregs. Together, these studies demonstrate that while
      expansion of Tregs using IL-2, prior to immunization or the onset of disease, can
      suppress the immune response, their role is limited after the antigen-specific
      response is triggered. Because IL-2 is used to treat certain types of cancers,
      and Tregs have applications in preventing the rejection of transplants, our
      studies also provide useful information on the use and limitations of Tregs in
      such clinical manifestations.

PMID- 22954714
TI  - Compressive properties of passive skeletal muscle-the impact of precise sample
      geometry on parameter identification in inverse finite element analysis.
AB  - Due to the increasing developments in modelling of biological material, adequate
      parameter identification techniques are urgently needed. The majority of recent
      contributions on passive muscle tissue identify material parameters solely by
      comparing characteristic, compressive stress-stretch curves from experiments and
      simulation. In doing so, different assumptions concerning e.g. the sample
      geometry or the degree of friction between the sample and the platens are
      required. In most cases these assumptions are grossly simplified leading to
      incorrect material parameters. In order to overcome such oversimplifications, in
      this paper a more reliable parameter identification technique is presented: we
      use the inverse finite element method (iFEM) to identify the optimal parameter
      set by comparison of the compressive stress-stretch response including the
      realistic geometries of the samples and the presence of friction at the
      compressed sample faces. Moreover, we judge the quality of the parameter
      identification by comparing the simulated and experimental deformed shapes of the
      samples. Besides this, the study includes a comprehensive set of compressive
      stress-stretch data on rabbit soleus muscle and the determination of static
      friction coefficients between muscle and PTFE.

PMID- 22954715
TI  - Sensitivity of flow simulations in a cerebral aneurysm.
AB  - The flow in a cerebral aneurysm on the Anterior Communicating Artery is simulated
      based on patient medical imaging. The sensitivity of the flow pattern is assessed
      with respect to variation of outflow split and geometric parameters. A comparison
      is made between the results from unsteady pulsatile computations and steady-state
      computations. The results show that for this case there is no significant
      sensitivity to pulsatile flow-rate variations. Steady-state and pulsatile
      simulations both predict a strong sensitivity to outflow split and geometric
      smoothing. It is therefore proposed to analyse the stability of aneurysmal flow
      with an extensive sensitivity study based on steady-state computations and use
      this sensitivity for rupture prediction.

PMID- 22954716
TI  - Stability analysis of a mathematical model in a microcosm with piecewise constant
      arguments.
AB  - In this paper, we have modeled a population density of a bacteria species in a
      microcosm by using a differential equation, [Formula in text] where t >= 0, the
      parameters r, alpha, beta(0) and beta(1) denote positive numbers ann [t] denotes
      the integer part of [Formula in text]. First, to obtain the local and global
      behaviors, the boundedness character and the periodic nature of the population
      density for bacteria, discrete solutions of differential Eq. (A) is investigated.
      Examinations of the stability characterization of (A) show that increasing of the
      population growth rate decreases the local stability of the positive equilibrium
      point. Due to this result we need to consider a second approximation to obtain
      stability of population density. This can be performed at low density by
      incorporating an Allee function to (A) at time t. For the theoretical results
      obtained here we give an example by taking some parameter values from
      experimental data of bacteria populations [8] and show that the experimental and
      theoretical results for both models with and without Allee effect are in good
      agreement.

PMID- 22954717
TI  - Serotonergic control of ingestive and post-ingestive behaviors in pigeons
      (Columba livia): the role of 5-HT1A receptor-mediated central mechanisms.
AB  - Central injections of serotonin (5-HT) produce hyperdipsic and hypnogenic
      behavioral effects that are correlated to decreased Fos-immunorreactivity of 5-HT
      neurons in free-feeding pigeons. We herein (1) probed the role of 5-HT(1A)
      receptors on the 5-HT- or 8-OH-DPAT-evoked postprandial behaviors and (2)
      described the sleep-waking states (waking, W; drowsiness, D; slow-wave sleep,
      SWS; rapid-eye movement sleep, REMS) and sleep architecture of free-feeding
      pigeons after these treatments. Latency, frequency and duration of feeding,
      drinking, preening, exploratory and sleep-like behaviors (SLB) were examined
      after intracerebroventricular (ICV) injections of 5-HT (0, 50 or 150 nmol) or 8
      OH-DPAT (DPAT, 0 or 30 nmol) in pigeons pretreated with the 5-HT(1A) antagonist
      WAY100635 (WAY, 0, 0.1, 0.3 or 1 nmol). Additionally, the acute (1h) waking-sleep
      related electrographic activity in the hippocampus (HP) was examined after ICV
      injections of 5-HT (150 or 300 nmol) or DPAT (30 or 60 nmol) in pigeons
      pretreated with WAY (0 or 1 nmol). 5-HT and DPAT acutely increased drinking and
      then sleep: all doses of WAY attenuated the 5-HT (50 nmol) -induced dipsogenic
      effect, but left unchanged the effects of the 150 nmol 5-HT dose. The WAY 0.1
      nmol dose blocked the SLB induced by the 5-HT 50 nmol dose. Given before the
      vehicle (VEH) injections, WAY does not affect water or food intake, but increased
      the SLB duration at all doses. DPAT injections increased feeding, drinking and
      SLB. All the WAY doses attenuated the DPAT-induced drinking and feeding
      responses, and the WAY 0.1 and 0.3 nmol doses reduced DPAT-induced SLB. DPAT or 5
      HT injections decreased the duration of electrographically-determined waking,
      increased the durations of D and induced the emergence of SWS and REMS states
      indistinguishable from the hippocampal EEG associated with spontaneous sleep, as
      judged from visual and spectral analysis. WAY (1 nmol) increased SWS and D, and
      potentiated the 5-HT- and DPAT-induced SWS. These data suggest that 5-HT-induced
      drinking depends on the activation of presynaptic 5-HT(1A) receptors, while 5
      HT(1A) autoreceptor activation contributes to the 5-HT-induced sleep. 5-HT
      induced drinking and sleep behaviors may thus be provoked by a 5-HT(1A)-evoked,
      rebound-like reduction in central 5-HTergic activity. These data also indicate
      that an ongoing, tonic and inhibitory influence of central 5-HT circuits may
      participate in the control of feeding, drinking and rest behaviors in pigeons
      during the wake, nibbling diurnal state. These mechanisms appear to be comparable
      to those found in mammals, suggesting that they may represent a conserved,
      plesiomorphic functional trait of the amniotes brain.

PMID- 22954719
TI  - Natural selection and the attention deficit hyperactivity disorder-obsessive
      compulsive personality disorder theory of human behavior.

PMID- 22954718
TI  - Ephrin-A5 deficiency alters sensorimotor and monoaminergic development.
AB  - The Eph receptors and their ligands, the ephrins, play an important role during
      neural development. In particular, ephrin-A5 is highly expressed in the
      developing nervous system in several brain regions including the olfactory bulb,
      frontal cortex, striatum and hypothalamus. Although a number of studies have
      characterized the expression of ephrin-A5 in these regions, very little is known
      about the functional consequences that might follow alterations in the expression
      of this ligand. Previously, we demonstrated that ephrin-A5 acts as a guidance
      molecule regulating the trajectory of the ascending midbrain dopaminergic
      pathways. In light of this finding and the critical role of dopamine in
      modulating a number of behaviors, we sought to determine whether loss of ephrin
      A5 altered neurobehavioral development. Our results indicate that ephrin-A5-null
      mice exhibit delays in reaching developmental milestones and in the maturation of
      motor skills. In addition, they exhibit increased locomotor activity and reduced
      levels of brain monoamines. Therefore, we conclude that ephrin-A5 expression
      appears to be critical for proper development of central monoaminergic pathways
      and that its loss results in a number of neurodevelopmental abnormalities.
      Because alterations in monoamine function are associated with a variety of
      neurodevelopmental disorders, these data suggest that further study on the
      potential role of ephrin-A5 in such disorders is warranted.

PMID- 22954720
TI  - ITX 5061 quantitation in human plasma with reverse phase liquid chromatography
      and mass spectrometry detection.
AB  - BACKGROUND: ITX 5061 is a highly potent small molecule inhibitor of scavenger
      receptor-B1, an integral transmembrane protein that is found in liver cells and
      is actively involved in the transport of HCV into hepatocytes. Currently, ITX
      5061 is being investigated in monoinfected hepatitis C patients in a proof-of
      concept clinical trial carried out by the AIDS Clinical Trial Group (ACTG).
      METHODS: To provide quantitative results in human plasma for pharmacokinetic
      analysis, an assay for ITX 5061 was validated. ITX 5061 and the internal
      standard, a deuterated analogue, were separated by isocratic reverse phase
      chromatography using a Polar RP column (Phenomenex Synergi(TM); 2.0 mm * 50 mm, 4
      um) and detected via electrospray coupled to a triple quadrupole mass
      spectrometer with a run time of 5 min. Multiple reaction monitoring in positive
      mode was used with ITX 5061 at 585/114 m/z and the internal standard at 592/122
      m/z with a linear range of 2.50-5,000 ng/ml. Human plasma was extracted using a
      protein precipitation combing 400 ul of acetonitrile with 100 ul of EDTA plasma.
      RESULTS: The interassay variation ranged from 1.19 to 13.2%, while the intraassay
      variation ranged from 0.394 to 12.9% over 6 days of testing. The method was
      successfully applied to the samples collected for the ACTG Protocol A5277. Plasma
      concentrations at 1 h and 24 h following 150 mg ITX 5061 daily in HCV
      monoinfected patients (n=3) ranged from 138 to 518 ng/ml and 33 to 111 ng/ml,
      respectively. CONCLUSIONS: The ITX 5061 assay is accurate and reproducible with a
      wide linear range and will be used for pharmacokinetic analysis and dose-finding
      studies in HCV-monoinfected patients.

PMID- 22954721
TI  - Treatment of patients with early and advanced Parkinson's disease with rotigotine
      transdermal system: age-relationship to safety and tolerability.
AB  - Although dopamine agonists (DAs) are sometimes perceived as poorly tolerated by
      the elderly, there is little clinical evidence to support these concerns. Safety
      and tolerability of rotigotine have been demonstrated in four 6-month randomized
      placebo-controlled studies: two in early Parkinson's disease (PD) and two in
      advanced PD. A post hoc analysis of data from these pivotal trials was carried
      out to compare the adverse event (AE) profiles of younger and older patient
      populations. Data from early and advanced PD trials were separately pooled and
      evaluated using two age cut-offs (<65 vs. >= 65 years; <75 vs. >= 75 years). For
      most AEs, no age-related differences in incidence were observed. In the early PD
      pool, nausea (38% vs. 30%) and headache (15% vs. 9%) were more frequent in
      younger (<65 years) compared with older (>= 65 years) patients using the 65-year
      age cut-off. Using the 75-year cut-off, nausea (36% vs. 21%) was more frequent in
      younger patients (<75 years) and dizziness (15% vs. 28%) was more frequent in
      older patients (>= 75 years). In the advanced PD pool, nausea was more frequent
      in younger patients using the 65-year age cut-off (24% vs. 19%) and falls were
      more frequent in older patients using the 75-year age cut-off (8% vs. 13%). In
      this relatively healthy population which included only few patients aged 75 years
      or older, rotigotine was generally well tolerated regardless of age. Data from
      more representative PD populations are required to fully assess potential risks
      of DA therapy in elderly patients.

PMID- 22954722
TI  - Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human
      breast cancer cells with different glycolytic attitude by affecting distinct
      signaling pathways.
AB  - Galloflavin (GF), a recently identified lactate dehydrogenase inhibitor, hinders
      the proliferation of cancer cells by blocking glycolysis and ATP production. The
      aim of the present experiments was to study the effect of this compound on breast
      cancer cell lines reproducing different pathological subtypes of this tumor: MCF
      7 (the well differentiated form), MDA-MB-231 (the aggressive triple negative
      tumor) and MCF-Tam (a sub-line of MCF-7 with acquired tamoxifen resistance). We
      observed marked differences in the energetic metabolism of these cell lines.
      Compared to MCF-7 cells, both MDA-MB-231 and MCF-Tam cells exhibited higher LDH
      levels and glucose uptake and showed lower capacity of oxygen consumption. In
      spite of these differences, GF exerted similar growth inhibitory effects. This
      result was explained by the finding of a constitutively activated stress response
      in MDA-MB-231 and MCF-Tam cells, which reproduce the poor prognosis tumor forms.
      As a further proof, different signaling pathways were found to be involved in the
      antiproliferative action of GF. In MCF-7 cells we observed a down regulation of
      the ERalpha-mediated signaling needed for cell survival. On the contrary, in MCF
      Tam and MDA-MB-231 cells growth inhibition appeared to be contributed by an
      oxidative stress condition. The prevalent mechanism of cell death was found to be
      apoptosis induction. Because of the clinical relevance of breast cancer forms
      having the triple negative and/or chemoresistant phenotype, our results showing
      comparable effects of GF even on aggressively growing cells encourage further
      studies to verify the potential of this compound in improving the chemotherapy of
      breast cancer.

PMID- 22954723
TI  - Human leukocyte antigen-haploidentical stem cell transplantation using T-cell
      replete bone marrow grafts.
AB  - PURPOSE OF REVIEW: Once considered too dangerous for all but the sickest of
      patients, partially human leukocyte antigen (HLA)-mismatched, or HLA
      haploidentical, related donor bone marrow transplantation (haploBMT) has seen a
      revival, thanks to the reduced intensity conditioning (RIC) regimens and graft
      versus-host disease (GVHD) prophylaxis with high-dose posttransplantation
      cyclophosphamide (PT/Cy). RECENT FINDINGS: RIC haploBMT with high-dose PT/Cy is
      associated with a cumulative incidence of acute grades II-IV GVHD of
      approximately 30% and incidences of chronic GVHD and nonrelapse mortality (NRM)
      less than 15%. These results have been confirmed in single and multicenter
      clinical trials. PT/Cy appears to nullify the detrimental effects of HLA
      mismatching on the outcome of haploBMT, thereby permitting the selection of haplo
      donors based upon criteria other than HLA matching. Overall and event-free
      survivals of RIC haploBMT compare favorably to the outcomes of RIC unrelated
      adult donor or umbilical cord blood stem cell transplantation. SUMMARY: With its
      improved toxicity profile, haploBMT is a feasible alternative for patients who
      lack an HLA-matched donor and can now be applied to treat patients with
      nonmalignant disorders.

PMID- 22954724
TI  - Current efforts to reduce the risk of syncope among young blood donors.
AB  - PURPOSE OF REVIEW: This review examines recent research on syncope after whole
      blood donation and efforts by blood centers to improve safety for young blood
      donors. RECENT FINDINGS: Young (16-18-year-old) volunteers contribute about 14%
      of the whole blood collected by the American Red Cross each year. Although quite
      safe, blood donation has some attendant risk, and syncopal reactions are more
      common among the youngest donors. Precautionary measures include predonation
      education, environmental controls, water ingestion shortly before phlebotomy, and
      distraction and muscle tension during collection. American Red Cross and Blood
      Systems, Inc. introduced new criteria to select donors with an estimated blood
      volume above 3.5 l. The changes led to about a 20% decrease in reactions among
      young blood donors, with the greatest benefit observed among the youngest, most
      susceptible donors. SUMMARY: Although the risk to blood donors cannot be
      eliminated, a systematic approach can achieve a significant and sustained
      improvement among vulnerable donor populations. Further research should explore
      novel ways to reduce the risk of syncope and prevent the uncommon, but
      potentially serious, associated injuries after whole blood donation.

PMID- 22954725
TI  - Recent advances in the analysis of fetal nucleic acids in maternal plasma.
AB  - PURPOSE OF REVIEW: Noninvasive prenatal diagnosis can be achieved by analyzing
      cell-free fetal DNA in maternal plasma. The fact that circulating fetal DNA
      represents only a minor fraction of the DNA that is present in maternal plasma
      has presented analytical challenges for a number of applications. In this review,
      we discuss such challenges and how they have been resolved by recent developments
      in the field. RECENT FINDINGS: Digital molecular counting methods, such as
      digital PCR and massively parallel sequencing, have enabled high quantitative
      precision for maternal plasma DNA analysis. Noninvasive prenatal analysis of
      monogenic disease mutations has been achieved by identifying small quantitative
      differences between the mutant and wild-type alleles in maternal plasma. By
      measuring the small increment in the fractional concentrations of DNA derived
      from potentially aneuploid chromosomes in maternal plasma, fetal chromosomal
      aneuploidies have been detected with high diagnostic accuracies. SUMMARY:
      Recently, advances in molecular technologies have enhanced the diagnostic
      applications of maternal plasma DNA analysis for noninvasive prenatal diagnosis.
      We foresee that this technology could play an increasingly important role in
      prenatal investigations.

PMID- 22954726
TI  - Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune
      thrombocytopenia.
AB  - PURPOSE OF REVIEW: The purpose of the review is to show the similarities between
      haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal
      alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges
      related to the current endeavours of developing a prophylaxis against FNAIT. The
      rationale for this prophylaxis is similar to the prophylaxis which has been used
      with great success for the last 40 years against RhD-associated HDFN. The idea is
      to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti
      HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after
      delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian
      screening and intervention study on FNAIT have indicated that about 75% of women
      with antibodies against HPA-1a are immunized in relation to delivery. This
      observation leads to the possibility of preventing HPA-1a-associated FNAIT in the
      same way as today's prevention of HDFN. Results from a proof-of-concept study in
      a murine FNAIT model have shown that the production of alloantibodies against
      platelets can be suppressed by administrating antiplatelet antibodies after the
      antigenic challenge. Even more interesting, the prophylactic antiplatelet
      antibodies could also significantly reduce the clinical consequences of FNAIT in
      this FNAIT model. SUMMARY: These novel observations have paved the way for
      clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will
      be carried out by a European Union-funded consortium. If the results from the
      clinical trial are favourable, there is a chance that a medicinal product for the
      prevention of FNAIT will be available within this decade.

PMID- 22954727
TI  - Blood group phenotypes resulting from mutations in erythroid transcription
      factors.
AB  - PURPOSE OF REVIEW: This review describes the genetics of unusual blood group
      phenotypes, particularly those with altered expression of Lutheran antigens, and
      how this area of study has informed our understanding of erythropoiesis in
      general and haemoglobin switching in particular. RECENT FINDINGS: Mutations in
      erythroid transcription factors GATA1 (GATA1 binding protein 1) and KLF1 (Kruppel
      like factor 1) cause benign and disease phenotypes in humans [X-linked Lu(a-b-)
      phenotype, In(Lu) blood group phenotype, hereditary persistence of foetal
      haemoglobin, borderline HbA(2), and congenital dyserythropoietic anaemia (CDA)].
      These studies explain the occurrence of rare blood group phenotypes with
      simultaneous altered expression of antigens from several blood group systems and
      illuminate the role of KLF1 in gamma and delta globin gene regulation. SUMMARY:
      The study of rare blood group phenotypes is a potent tool for discovery of
      mutations in human genes. Elucidation of the molecular basis of the rare In(Lu)
      phenotype revealed the first mutations in human KLF1. Subsequently, numerous
      additional mutations have been described, one of which causes a rare form of CDA.
      Analysis of the X-linked Lu(a-b-) phenotype revealed a mutation in the C-terminal
      domain of human GATA1. The apparent sensitivity of the Lutheran glycoprotein to
      alterations in GATA1 and KLF1 activity suggest that it could be a useful
      biomarker of erythroid transcription factor mutation.

PMID- 22954728
TI  - Natural killer cell alloreactivity 10 years later.
AB  - PURPOSE OF REVIEW: This article reviews the impact of natural killer (NK) cell
      alloreactivity on hematopoietic cell transplantation since it was first observed
      in haploidentical transplant recipients 10 years ago. RECENT FINDINGS: Research
      has established 'missing self-recognition' as the mechanism underlying NK cell
      mediated graft-versus-leukemia effects in T-cell-depleted haploidentical
      hematopoietic cell transplantation and has clarified optimal transplantation
      protocols to harness NK cell alloreactivity. SUMMARY: In the past decade,
      clinical studies have shown that the benefits of donor-versus-recipient NK cell
      alloreactivity in haploidentical transplantation are triggered by specific human
      leukocyte antigen (HLA) class I mismatches. Donor HLA is crucial for driving NK
      cell education so that reconstituting NK cells mature as donor-tolerant and
      recipient-alloreactive. Transplantation of large doses of extensively T-cell
      depleted hematopoietic grafts with no posttransplant immune suppression was found
      to be essential for development of NK cell alloreactivity. Clinical trials
      demonstrated that donor-versus-recipient NK cell alloreactivity is a key
      therapeutic element in haploidentical transplants for acute myeloblastic leukemia
      in adults and acute lymphoblastic leukemia in children. Moreover, in pilot
      studies, mature haploidentical NK cells were transiently transferred into
      lymphoablated patients with acute leukemia in remission. The results showed NK
      cell therapy may be a promising strategy for consolidating leukemia remission. In
      line with the notion that NK cell function is regulated by a balance between
      activating and inhibitory receptors, in the matched transplant setting,
      transplantation from donors possessing certain activating NK receptors
      (activating killer cell immunoglobulin-like receptors) appeared to protect from
      relapse and improved survival.

PMID- 22954729
TI  - Granulocyte-mobilized bone marrow.
AB  - PURPOSE OF REVIEW: In the last few years, mobilized peripheral blood has overcome
      bone marrow as a graft source, but, despite the evidence of a more rapid
      engraftment, the incidence of chronic graft-versus-host disease is significantly
      higher with, consequently, more transplant-related mortality on the long follow
      up. Overall, the posttransplant outcome of mobilized peripheral blood recipients
      is similar to that of patients who are bone marrow grafted. More recently, the
      use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor
      priming has been introduced in the transplant practice. Herein, we review
      biological acquisitions and clinical results on the use of G-CSF-primed bone
      marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell
      transplantation. RECENT FINDINGS: G-CSF the increases the HSC compartment and
      exerts an intense immunoregulatory effect on marrow T-cells resulting in the
      shift from Th1 to Th2 phenotype with higher production of anti-inflammatory
      cytokines. The potential advantages of these biological effects have been
      translated in the clinical practice by using G-CSF primed unmanipulated bone
      marrow in the setting of transplant from human leukocyte antigen (HLA)
      haploidentical donor with highly encouraging results. SUMMARY: For patients
      lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated
      bone marrow from a haploidentical donor combined with an intense in-vivo
      immunosuppression is a valid alternative achieving results that are well
      comparable with those reported for umbilical cord blood, HLA-matched unrelated
      peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

PMID- 22954730
TI  - Characterization of recombinant nitrile-specifier proteins (NSPs) of Arabidopsis
      thaliana: dependency on Fe(II) ions and the effect of glucosinolate substrate and
      reaction conditions.
AB  - Glucosinolates are plant secondary metabolites that are part of a plant defence
      system against pathogens and pests, the myrosinase-glucosinolate system, in which
      glucosinolates get activated by enzymic degradation through thioglucoside
      glucohydrolases called myrosinases. Epithiospecifier protein (ESP) and nitrile
      specifier proteins (NSPs) divert myrosinase-catalyzed hydrolysis of a given
      glucosinolate from the formation of isothiocyanate to that of epithionitrile
      and/or nitrile. As the biological activity of glucosinolate hydrolysis products
      varies considerably, a detailed characterization of these specifier proteins is
      of utmost importance to understand their biological role. Therefore, the
      Arabidopsis thaliana AtNSP1, AtNSP2 and AtNSP5 and a supposed ancestor protein
      AtNSP-like1 were expressed in Escherichia coli and the activity of the purified
      recombinant proteins was tested in vitro on three highly different glucosinolates
      and compared to that of purified AtESP. As previously reported, only AtESP showed
      epithiospecifier activity on 2-propenylglucosinolate. We further confirmed that
      purified AtNSP1, AtNSP2 and AtNSP5, but not the ancestor AtNSP-like1 protein,
      show nitrile-specifier activity on 2-propenylglucosinolate and
      benzylglucosinolate. We now show for the first time that in vitro AtNSP1, AtNSP2
      and AtNSP5 are able to generate nitrile from indol-3-ylmethylglucosinolate. We
      also tested the effect of different Fe(II) ion concentrations on the nitrile
      specifier activity of purified AtNSP1, AtNSP2 and AtNSP5 on 2
      propenylglucosinolate and benzylglucosinolate. AtNSP-related nitrile production
      was highly dependent on the presence of Fe(II) ions in the reaction assay. In the
      absence of added Fe(II) ions nitriles were only detected when benzylglucosinolate
      was incubated with AtNSP1. While AtNSP1 also exhibited overall higher nitrile
      specifier activity than AtNSP2 and AtNSP5 at a given Fe(II) ion concentration,
      the pattern of nitrile formation in relation to Fe(II) ion concentrations
      depended on the AtNSP and the glucosinolate substrate. The pH of the solution
      also affected the reaction outcome, with a higher proportion of nitrile being
      produced at the higher pH for AtNSP2 and AtNSP5.

PMID- 22954731
TI  - Chemical and biological evaluation of nephrocizin in protecting nerve growth
      factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity.
AB  - The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an
      experimental model of Parkinson's disease. This model is crucial in the search
      for compounds that diminish 6-OHDA-induced nerve growth factor (NGF)
      differentiated PC12 cell death. Nephrocizin (luteolin-7-O-beta-D
      glucopyranoside), a flavone glycoside, was isolated from widely distributed
      plants. The protective effects of pre-treatment with nephrocizin on the induced
      neurotoxicity in PC12 cells by 6-OHDA and its oxidative products, H2O2-, and p
      quinone, were evaluated herein. Nephrocizin promoted cell viability, scavenged
      ROS-related products, increased cellular glutathione (GSH) levels, and reduced
      caspase-3 and -8 activities in 6-OHDA-, H2O2-, or p-quinone-treated PC12 cells.
      Furthermore, nephrocizin-conjugated metabolites in PC12 cells were identified
      with the boronate-affinity method and LC-MS technology, and preferential
      regioselectivity at the C2' and C5' positions by the nephrocizin-GSH (or NAC)
      adduct method was observed. These lines of evidence established that nephrocizin
      could form a dimer to diminish the intracellular ROS. These results demonstrate
      the first neuroprotective mechanism of nephrocizin against 6-OHDA-, H2O2- or p
      quinone-induced cytotoxicity in PC12 cells via chemical and biological studies.
      These dietary antioxidants are potential candidates for use in intervention in
      neurodegenerative diseases.

PMID- 22954732
TI  - Untapped mutualistic paradigms linking host plant and endophytic fungal
      production of similar bioactive secondary metabolites.
AB  - The biosynthetic potential of endophytic fungi has gained impetus in recent times
      owing to the continual discovery of fungal endophytes capable of synthesizing
      plant compounds. However, the sustained production of the desired plant compounds
      has not yet been achieved using endophytes. It is thus imperative to investigate
      the diverse interactions that endophytes have with coexisting endophytes, host
      plants, insect pests, and other specific herbivores. The precise role of these
      associations on the endophytic production of host plant compounds is mostly
      overlooked and open to future discoveries. Here, highlighted are the implications
      of the poorly investigated links and molecular mechanisms that might trigger
      similar chemical responses in both plants and endophytes. Elucidating such
      connections can not only enhance the understanding of evolution of complex
      defense mechanisms in plants and associated organisms, but also help in the
      sustained production of plant compounds using endophytes harbored within them.

PMID- 22954733
TI  - Travel Health Advisory Group: a joint travel industry and travel health Special
      Interest Group promoting healthy travel in Australia.
AB  - The Travel Health Advisory Group (THAG), established in 1997, is a joint
      initiative between the travel industry and travel health professionals in
      Australia that aims to promote healthy travel. THAG seeks to promote cooperation
      in improving the health of travellers between the travel industry and travel
      medicine professionals and to raise public awareness of the importance of travel
      health. From 2011, THAG has been a Special Interest Group of The Australasian
      College of Tropical Medicine and its membership has been active in several areas,
      including web-based travel health information, travel health promotion, media
      releases, research and education in Australia. Information is given on the
      objectives, membership and an overview of the various activities of the group.

PMID- 22954734
TI  - Act 2 for the affordable care act: fodder for health care management research.

PMID- 22954735
TI  - Biological activity evaluation and structure-activity relationships analysis of
      ferulic acid and caffeic acid derivatives for anticancer.
AB  - The anticancer activities of alkyl esters and NO-donors of ferulic acid (FA) and
      caffeic acid (CA) were assessed by a high-throughout screening (HTS) method, and
      the structure-activity relationships were described. CA alkyl esters had better
      anticancer activities than FA alkyl esters with the same alkyl substituent. Mono
      nitrates and phenylfuroxan nitrates were more potent than the dual nitrates.
      Phenylsulfonylfuroxan nitrates of FA, especially compounds 8b-8d, exhibited more
      potent activities in anticancer.

PMID- 22954736
TI  - Melanin concentrating hormone receptor 1 (MCHR1) antagonists-Still a viable
      approach for obesity treatment?
AB  - Obesity is a global epidemic associated with multiple severe diseases. Several
      pharmacotherapies have been investigated including the melanin concentrating
      hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are
      described with a specific perspective on different chemotypes investigated in
      efforts to overcome hERG liabilities while having orally active, potent and
      selective compounds with sufficient brain penetration. A chemometric comparison
      of ~2000 diverse MCHR1 and ~1000 diverse hERG ligands underline the structural
      similarities. A binding pocket analysis of a MCHR1 model and recent X-ray
      structures of GPCRs invoked in selectivity issues indicate a way to support
      future drug design.

PMID- 22954737
TI  - Pyrazolopyridine inhibitors of B-Raf(V600E). Part 4: rational design and kinase
      selectivity profile of cell potent type II inhibitors.
AB  - Cell potent inhibitors of B-Raf(V600E) that bind to the kinase in the DFG-out
      conformation are reported. These compounds utilize the hinge-binding group and
      lipophilic linker from a previously disclosed series of B-Raf(V600E) inhibitors
      that bind to the kinase in an atypical DFG-in, alphaC-helix-out conformation.
      This new series demonstrates that DFG-out kinase inhibitors can be rationally
      designed from related inhibitors which utilize an unconventional binding mode.
      Kinase selectivity profiles are compared. The pattern of kinase selectivity was
      found to be determined by the feature of the inhibitor which extends into the
      back pocket of the kinase and leads to the kinase conformation, rather than by
      the hinge-binding group or other minor modifications.

PMID- 22954738
TI  - Superior petrosal sinus: hemodynamic features in normal and cavernous sinus dural
      arteriovenous fistulas.
AB  - BACKGROUND AND PURPOSE: Normal hemodynamic features of the superior petrosal
      sinus and their relationships to the SPS drainage from cavernous sinus dural
      arteriovenous fistulas are not well known. We investigated normal hemodynamic
      features of the SPS on cerebral angiography as well as the frequency and types of
      the SPS drainage from CSDAVFs. MATERIALS AND METHODS: We evaluated 119 patients
      who underwent cerebral angiography by focusing on visualization and hemodynamic
      status of the SPS. We also reviewed selective angiography in 25 consecutive
      patients with CSDAVFs; we were especially interested in the presence of drainage
      routes through the SPS from CSDAVFs. RESULTS: In 119 patients (238 sides), the
      SPS was segmentally (anterior segment, 37 sides; posterior segment, 82 sides) or
      totally (116 sides) demonstrated. It was demonstrated on carotid angiography in
      11 sides (4.6%), receiving blood from the basal vein of Rosenthal or
      sphenopetrosal sinus, and on vertebral angiography in 235 sides (98.7%),
      receiving blood from the petrosal vein. No SPSs were demonstrated with venous
      drainage from the cavernous sinus. SPS drainage was found in 7 of 25 patients
      (28%) with CSDAVFs. CSDAVFs drained through the anterior segment of SPS into the
      petrosal vein without draining to the posterior segment in 3 of 7 patients (12%).
      CONCLUSIONS: The SPS normally works as the drainage route receiving blood from
      the anterior cerebellar and brain stem venous systems. The variation of
      hemodynamic features would be related to the relatively lower frequency and 2
      different types of SPS drainage from CSDAVFs.

PMID- 22954739
TI  - CT and MR imaging findings of sinonasal schwannoma: a review of 12 cases.
AB  - Schwannomas are benign tumors that are rarely found in the sinonasal cavity, and
      the purpose of this study was to characterize the CT and MR imaging findings of
      12 patients with surgically proved sinonasal schwannomas. Assessed features
      include location, margin, shape, size, internal architecture, pattern and degree
      of enhancement, and associated bony wall changes. The characteristic CT and MR
      imaging findings of sinonasal schwannoma include a well-defined soft-tissue mass,
      most frequently occurring in the nasal cavity and ethmoid sinus with pressure
      remodeling of the adjacent bony wall. The tumors were isoattenuating on CT and
      predominantly isointense on both T1- and T2-weighted MR images, compared with the
      brain stem. Mild contrast enhancement on CT and strong enhancement on MR images
      were also demonstrated in most of the tumors, and cystic or hemorrhagic changes
      were noted in 2 cases.

PMID- 22954740
TI  - Comments on an article by Ginat and Schatz.

PMID- 22954741
TI  - Impaired default mode network on resting-state FMRI in children with medically
      refractory epilepsy.
AB  - BACKGROUND AND PURPOSE: Resting-state networks including the DMN have been shown
      to be abnormal in adults with temporal lobe epilepsy. However, little is known
      about the DMN in children with medically refractory epilepsy. The aim was to
      determine whether there was a difference in the DMN in children with medically
      refractory epilepsy relative to controls. MATERIALS AND METHODS: Eleven children
      with medically refractory epilepsy and 11 age-matched healthy controls underwent
      resting-state fMRI. IC analysis was used to identify the DMN. A random-effects
      analysis was performed on the Z-maps of the DMN within each group and between
      groups. We calculated the temporal correlation coefficients of pairs of ROIs:
      PCC/PCUN, mPFC, and left and right lateral parietal cortices. The relations
      between z scores of temporal correlation coefficients of pairs of ROIs and
      clinical seizure parameters and IQ were assessed. RESULTS: The patients
      demonstrated decreased DMN connectivity in the PCC/PCUN, bilateral lateral
      parietal cortex, and anterior and midcingulate relative to controls. There was
      reduced connectivity between the mPFC-right lateral parietal cortex, the PCC/PCUN
      left lateral parietal cortex, and the PCC/PCUN-right lateral parietal cortex
      pairs of ROIs in patients compared with controls. There were no significant
      correlations between the z scores of temporal correlation coefficients of the 6
      pairs of ROIs in patients and age of seizure onset, duration of epilepsy, number
      of medications, seizure frequency, and IQ. CONCLUSIONS: We have found reduced
      connectivity in the DMN in children with medically refractory epilepsy. Further
      studies are needed to determine whether different seizure types have different
      effects on the DMN and whether the impaired connectivity is related to cognitive
      functions subserved by the DMN.

PMID- 22954742
TI  - CT-guided cervical transforaminal steroid injections: where should the needle tip
      be located?
AB  - BACKGROUND AND PURPOSE: The aim of CT-guided CTSI is to inject medication into
      the foraminal region where the nerve root is inflamed. The optimal location for
      needle placement and therapeutic delivery, however, remain uncertain. The purpose
      of this study was to investigate how needle positioning and angle of approach
      impact the transforaminal distribution of injectate. MATERIALS AND METHODS: We
      retrospectively reviewed fluoroscopic images from 90 CT-guided CTSI procedures
      for needle-tip location, needle angle, and contrast distribution. Needle-tip
      position was categorized as either foraminal zone, junctional, or extraforaminal.
      Distribution of contrast injected immediately before steroid administration was
      categorized as central epidural, intraforaminal, or extraforaminal in location.
      Needle-tip location and angle were correlated with contrast distribution.
      RESULTS: The needle tip was most commonly placed in the junctional position (36
      cases, 40%), followed by foraminal (30 cases, 33%) and extraforaminal (24 cases,
      27%) locations. Intraforaminal contrast distribution was highest when the needle
      location was foraminal (30/30, 100%) or junctional (35/36, 97%), compared with
      extraforaminal (7/24, 29%) (P value <.0001). There was no relationship between
      needle angle and contrast distribution. CONCLUSIONS: Needle-tip location at the
      outer edge of the neural foramen (junctional location) correlated well with
      intraforaminal distribution of contrast for CT-guided CTSI and compared favorably
      with injectate distribution following foraminal zone needle positioning.
      Junctional needle positioning may be preferred over the foraminal zone by some
      proceduralists. Extraforaminal needle positioning resulted in less favorable
      contrast distribution, which may significantly diminish the therapeutic efficacy
      of CTSI.

PMID- 22954743
TI  - Comparison of MR imaging findings between extraligamentous and subligamentous
      disk herniations in the lumbar spine.
AB  - BACKGROUND AND PURPOSE: The method of treating an HIVD in the lumbar spine may
      depend on the integrity of the PLL. The purpose of this study was to analyze and
      compare the MR imaging findings of extraligamentous and subligamentous HIVDs in
      the lumbar spine. MATERIAL AND METHODS: One hundred seventeen patients (M/F =
      71:46; mean age, 47 years; age range, 15-79 years) underwent lumbar spine MR
      imaging and disk surgery (extraligamentous/subligamentous = 66:51) from May 2003
      to November 2006. Two radiologists in consensus retrospectively reviewed all MR
      images, focusing on 10 criteria. RESULTS: The following 5 criteria are suggestive
      of extraligamentous HIVD in the lumbar spine: 1) spinal canal compromised for
      more than half its dimension, 2) internal signal difference in the HIVD, 3) an
      ill-defined margin of the HIVD, 4) disruption of the continuous low-signal
      intensity line covering the HIVD, and 5) the presence of an internal dark line in
      the HIVD (P < .05). When we combined these 5 MR imaging criteria, the
      sensitivity, specificity, accuracy, and odds ratio were 77.3%, 74.5%, 76.1%, and
      9.93 (P < .0001). CONCLUSIONS: Our proposed 5 MR imaging criteria will be helpful
      in differentiating extraligamentous and subligamentous HIVDs in the lumbar spine.

PMID- 22954744
TI  - MRI characterization and longitudinal study of focal cerebellar lesions in a
      young tuberous sclerosis cohort.
AB  - BACKGROUND AND PURPOSE: There are few articles characterizing cerebellar lesions
      in patients with TSC and no published series documenting longitudinal evaluation
      of these lesions, to our knowledge. Recent suggestion of a correlation between
      autism and cerebellar lesions in patients with TSC heightens the importance of
      understanding these lesions. Our purpose was to characterize cerebellar lesions
      in a cohort of young patients with TSC with specific interest in assessing
      longitudinal changes. MATERIALS AND METHODS: We retrospectively reviewed MR
      images from 145 pediatric and young adult patients with tuberous sclerosis (mean
      age, 7.6 years). A number of imaging characteristics of cerebellar tubers were
      recorded, and patients were evaluated for SGAs. Patients with follow-up scans >3
      months from the original scan were further analyzed for longitudinal tuber
      characterization. RESULTS: There were 24.1% of patients with focal cerebellar
      lesions; 52.4% of patients with cerebellar lesions demonstrated change in imaging
      characteristics during longitudinal analysis. Fifty-one percent of the lesions
      were enhanced after gadolinium administration. Twenty percent of the patients
      with cerebellar lesions had pathologically confirmed SGAs compared with the
      incidence of 11% in the 145 patients with TSC reviewed. CONCLUSIONS: In our large
      cohort of young patients with TSC, cerebellar tubers were common and 52% of
      patients had tubers that changed with time. A higher percentage of patients with
      cerebellar lesions developed SGAs than patients with TSC without cerebellar
      lesions. Because this is the first reported longitudinal study of cerebellar
      lesions in TSC, further investigation may provide additional insight into TSC
      pathology and associated clinical manifestations, such as autism, developmental
      delay, and seizures.

PMID- 22954745
TI  - Electroneutral silica-based hybrid monolith for hydrophilic interaction capillary
      electrochromatography.
AB  - A novel electroneutral and polar silica-based hybrid monolith was developed by an
      in situ copolymerization of 2-hydroxyethylmethacrylate (HEMA) and polyhedral
      oligomeric silsesquioxane methacryl substituted (POSS-MA), and successfully
      employed for hydrophilic interaction capillary electrochromatography (HI-CEC). A
      good mechanical stability of the prepared monolith was gained with the
      permeability decreasing from 6.52*10(-14) m2 to 4.61*10(-14) m2 when mobile phase
      changed from ACN to water. A significant cathodal EOF was obtained through
      attracting ions from the mobile phase despite the fact that it was devoid of
      ionizable functional groups on the surface of stationary phases, and a typical HI
      CEC mechanism was achieved. The morphologies of the hybrid silica-based
      monolithic matrixes were observed, and the performance of this silica-based
      hybrid monolith was also investigated. Satisfactory column performances were
      carried out for both the neutral and charged analytes with HI-CEC. The analytes
      including uncharged amides and phenols, charged nucleic acid bases and
      nucleosides and enkephalins, were well separated with good peak symmetry. High
      separation efficiencies of charged alkaloids and enkephalins could get up to
      145,000 plates/m and 75,000 plates/m, respectively.

PMID- 22954746
TI  - Suitability of commercial hydrophobic interaction sorbents for temperature
      controlled protein liquid chromatography under low salt conditions.
AB  - The effect of temperature in the range from 10 degrees C to 40 degrees C and
      comparatively low ammonium sulfate (AS) concentrations of up to 0.5M on the
      adsorption of bovine serum albumin (BSA) on four different commercially available
      sepharose-based stationary phases was investigated. The determined isotherms were
      fitted by the Langmuir equation, and thermodynamic values were calculated by
      van't Hoff analysis. The adsorption of BSA onto the chromatographic resin Butyl
      Sepharose 4FF showed the strongest temperature influence; however, protein
      unfolding effects occurred when characterizing this system by dynamic column
      experiments, with an unfolded BSA fraction strongly attached to the sorbent. The
      percentage of the unfolding fraction was determined for different operating
      conditions and found to increase with the concentration of the cosmotropic salt,
      but even stronger with increasing temperature. Temperature-induced cyclic
      adsorption and desorption experiments were carried out to investigate the long
      term performance of Butyl Sepharose 4FF by applying purely temperature-controlled
      regeneration. Over a period of five cycles, the working capacity remained stable,
      but BSA also started to accumulate on the column due to incomplete regeneration.
      Finally, the possibility to fractionate different proteins with a single
      temperature shift was shown by the complete separation of lysozyme and BSA. The
      results presented indicate that temperature-induced binding and elution may offer
      a possibility to shift the operation conditions of HIC resins toward reduced salt
      concentrations, thus saving chemicals and facilitating salt removal in further
      downstream processing stages.

PMID- 22954747
TI  - Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT)
      gene are susceptible to complement mediated killing and defective in their
      metacyclogenesis.
AB  - Trypanosoma cruzi calreticulin (TcCRT) can hijack complement C1, mannan-binding
      lectin and ficolins from serum thus inhibiting the classical and lectin
      complement pathway activation respectively. To understand the in vivo biological
      functions of TcCRT in T. cruzi we generated a clonal cell line lacking one TcCRT
      allele (TcCRT+/-) and another clone overexpressing it (TcCRT+). Both clones were
      derived from the TCC T. cruzi strain. As expected, TcCRT+/- epimastigotes showed
      impairment on TcCRT synthesis, whereas TcCRT+ ones showed increased protein
      levels. In correlation to this, monoallelic mutant parasites were significantly
      susceptible to killing by the complement machinery. On the contrary, TcCRT+
      parasites showed higher levels of resistance to killing mediate by the classical
      and lectin but not the alternative pathway. The involvement of surface TcCRT in
      depleting C1 was demonstrated through restoration of serum killing activity by
      addition of exogenous C1. In axenic cultures, a reduced propagation rate of
      TcCRT+/- parasites was observed. Moreover, TcCRT+/- parasites presented a reduced
      rate of differentiation in in vitro assays. As shown by down- or upregulation of
      TcCRT expression this gene seems to play a major role in providing T. cruzi with
      the ability to resist complement system.

PMID- 22954748
TI  - A survey assessment of the recognition and treatment of psychocutaneous disorders
      in the outpatient dermatology setting: how prepared are we?
AB  - BACKGROUND: Dermatologists provide the bulk of psychocutaneous care; however,
      recent studies suggest that dermatologists believe they are largely underprepared
      to treat most psychocutaneous conditions. OBJECTIVE: We sought to identify gaps
      in psychodermatologic knowledge among practicing dermatologists in two academic
      institutions. METHODS: An online survey was sent to 59 dermatologists at the
      Massachusetts General Hospital (Boston, MA) and Brigham and Women's Hospital
      (Boston, MA) from July 2010 through October 2011. RESULTS: The response rate was
      40 of 59 (68%). More than 50% of dermatologists were comfortable making diagnoses
      for 8 of 10 psychocutaneous disorders. In all, 57% were comfortable making a
      diagnosis of depression. A total of 11% were comfortable starting
      antidepressants; 3%, antipsychotics; and 66%, medications for neuropathic pain.
      In all, 72%, 68%, and 21% of dermatologists never prescribe antidepressants,
      antipsychotics, or medications for neuropathic pain, respectively. Only 38%
      believed they were successful treating compulsive skin picking; 15%, body
      dysmorphic disorder; 27%, delusions of parasitosis; and 24%, depression.
      LIMITATIONS: Limitations include small sample size, data extraction from an
      academic setting, self-reporting of outcome measures, and response bias.
      CONCLUSION: Although the majority of the physicians surveyed believed they were
      capable of diagnosing psychocutaneous disease, very few were comfortable starting
      psychotropics or thought they were successful treating such conditions.

PMID- 22954749
TI  - Neuropilin-2 as a useful marker in the differentiation between Spitzoid malignant
      melanoma and Spitz nevus.
AB  - BACKGROUND: Spitzoid malignant melanoma (SMM) shares many histopathologic
      features with Spitz nevus (SN). The distinction between SMM and SN remains one of
      the most difficult diagnostic problems in dermatopathology. Neuropilin-2 (NRP2)
      is a cytoplasmic/cell surface protein that is a mediator of melanoma-endothelial
      cell interaction. OBJECTIVE: The aim of this study was to evaluate NRP2
      expression in SMM and SN and to determine whether it can reliably differentiate
      between the 2 groups. METHODS: We studied the expression of NRP2 in 19 cases of
      SMM and 19 cases of SN from Yale Spitzoid Neoplasm Repository, New Haven, Conn.
      RESULTS: All 19 cases of SMM (100%) expressed NRP2. Most SMM showed moderate- and
      high-intensity staining in the majority of the melanoma cells. Most of the SN
      (14/19, 74%) were negative for the marker. NRP2 labeled only 5 of 19 SN (26%) and
      all of them demonstrated mild staining intensity. NRP2(+) staining was
      statistically significant in differentiating SMM from SN (P < .05). LIMITATIONS:
      Small study size is a limitation. CONCLUSIONS: NRP2 expression in SMM and SN may
      be a useful adjunct marker, in addition to histopathologic evaluation, in the
      differentiation between these 2 entities.

PMID- 22954750
TI  - Context matters - the complex interplay between resistome genotypes and
      resistance phenotypes.
AB  - Application of metagenomic functional selections to study antibiotic resistance
      genes is revealing a highly diverse and complex network of genetic exchange
      between bacterial pathogens and environmental reservoirs, which likely
      contributes significantly to increasing resistance levels in pathogens. In some
      cases, clinically relevant resistance genes have been acquired from organisms
      where their native function is not antibiotic resistance, and which may not even
      confer a resistance phenotype in their native context. In this review, we attempt
      to distinguish the resistance phenotype from the resistome genotype, and we
      highlight examples of genes and their hosts where this distinction becomes
      important in order to understand the relevance of environmental niches that
      contribute most to clinical problems associated with antibiotic resistance.

PMID- 22954751
TI  - Effects of an antidepressant on neural correlates of emotional processing in
      patients with major depression.
AB  - We measured brain activation in patients with major depressive disorder when
      exposed to emotional pictures before and after antidepressant treatment. The
      participants included 18 first-episode unmedicated patients with current major
      depressive disorder and 18 age- and gender-matched control subjects. All subjects
      performed an emotional task during functional magnetic resonance imaging scanning
      at baseline and after 8 weeks of fluoxetine treatment. Unmedicated depressed
      patients showed lower accuracy rates (0.53+/-0.26) than did subjects in the
      control group (0.71+/-0.18) while viewing positive pictures. During exposure to
      positive stimuli, decreased activations were seen in the right insula (BA13) and
      left anterior cingulate cortex (BA32) in patients after antidepressant treatment.
      After antidepressant treatment, patients exhibited greater activation in the
      right middle frontal gyrus (BA8,9) in response to negative stimuli. Our results
      suggest that the prefrontal cortex, anterior cingulate cortex and insula may play
      key roles as biological markers for treatment response and as predictors of
      therapeutic success.

PMID- 22954752
TI  - Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia
      in cancer patients.
AB  - OBJECTIVES: In the current era of changing epidemiology of invasive pneumococcal
      disease, we aimed to assess the clinical features, antimicrobial susceptibility,
      vaccination status, serotypes, genotypes and outcomes of pneumococcal bacteremia
      in cancer patients. METHODS: Prospective observational analysis of all
      consecutive cancer adults admitted to a university hospital (January 2006-April
      2011). RESULTS: Of 971 episodes of bacteremia, 63 (6.5%) were caused by
      Streptococcus pneumoniae. Pneumonia was the most common source of pneumococcal
      bacteremia (84.1%). Although all isolated pneumococci were penicillin
      susceptible, resistance to ceftazidime was high (43%). The serotypes most
      frequently isolated were 19A and 14, and the most common genotypes were Spain(9V)
      ST156 and Denmark(14)-ST230. Only 23% of patients had received the 23-valent
      polysaccharide pneumococcal vaccine. This polysaccharide vaccine was found to
      cover 72.4% of the serotypes identified, whereas the 7-valent, 10-valent and the
      13-valent conjugate vaccines covered 24.1%, 29.3%, and 53.5% of serotypes
      respectively. The early case-fatality rate (<48 h) was 4.8% and overall case
      fatality rate (<30 days) 14.3%. CONCLUSIONS: Pneumococcal bacteremia, which
      complicates mainly pneumonia, is frequent in cancer patients and causes
      significant morbidity and case-fatality rate. Resistance to ceftazidime is
      particularly high. These findings should be considered when selecting antibiotic
      treatment for cancer patients presenting pneumonia.

PMID- 22954753
TI  - Prophylactic intra-aortic balloon pump in high-risk patients undergoing coronary
      artery bypass surgery:  a meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of a prophylactic
      intra-aortic balloon pump (IABP) in high-risk patients undergoing coronary artery
      bypass graft surgery. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS,
      Google Scholar, and reference lists of relevant articles were searched. We
      included only randomized controlled trials. Assessments for eligibility,
      relevance, and study validity and data extraction were performed in duplicate
      using prespecified criteria. Meta-analysis was carried out using fixed-effect and
      random-effect models. RESULTS: Seven publications fulfilled our eligibility
      criteria. There was no important statistical heterogeneity or publication bias
      among included studies. In total, 177 patients received prophylactic IABP and 168
      did not. Overall relative risk (RR) for hospital mortality in patients treated
      with prophylactic IABP was 0.255 [95% confidence interval (CI), 0.122-0.533;
      P<0.001; same results for both effect models]. Pooled RR for postoperative low
      cardiac output syndrome was 0.206 (95% CI, 0.109-0.389; P<0.001) for the fixed
      effect model and 0.219 (95% CI, 0.095-0.504; P<0.001) for the random-effect
      model. Patients treated with prophylactic IABP presented an overall difference in
      means for length of intensive care unit stay and hospital stay, which was lower
      than that in the control group (P<0.001 for both effect models). Only 7.4%
      (13/177) of patients who received prophylactic IABP developed complications at an
      insertion site, with no IABP-related death. CONCLUSION: This meta-analysis
      supports the use of prophylactic IABP in high-risk patients to reduce hospital
      mortality.

PMID- 22954754
TI  - Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the
      efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of
      haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.
AB  - Most atypical antipsychotic drugs (APDs), e.g. risperidone (RIS), produce more
      extensive blockade of brain serotonin (5-HT)(2A) than dopamine (DA) D(2)
      receptors. This distinguishes them from typical APDs, e.g. haloperidol (HAL). Our
      objective was to test the hypothesis that augmentation of low doses of RIS or HAL
      (2mg/day) with pimavanserin (PIM), a selective 5-HT(2A) inverse agonist, to
      enhance 5-HT(2A) receptor blockade, can achieve efficacy comparable to RIS,
      6mg/day, but with lesser side effects. In a multi-center, randomized, double
      blind, 6week trial, 423 patients with chronic schizophrenia experiencing a recent
      exacerbation of psychotic symptoms were randomized to RIS2mg+placebo (RIS2PBO),
      RIS2mg+PIM20mg (RIS2PIM), RIS6mg+PBO (RIS6PBO), HAL2mg+PBO (HAL2PBO), or
      HAL2mg+PIM20mg (HAL2PIM). Improvement in psychopathology was measured by the
      PANSS and CGI-S. The reduction in PANSS Total Score with RIS2PIM at endpoint was
      significantly greater than RIS2PBO: -23.0 vs. -16.3 (p=0.007), and not
      significantly different from the RIS6PBO group: -23.2 points. The percentage of
      patients with >=20% improvement at day 15 in the RIS2PIM group was 62.3%,
      significantly greater than the RIS6PBO (42.1%; p=0.01) and the RIS2PBO groups
      (37.7%; p=0.002). Weight gain and hyperprolactinemia were greater in the RIS6PBO
      group than the RIS2PIM group but there was no difference in extrapyramidal side
      effects (EPS). HAL2PBO and HAL2PIM were not significantly different from each
      other in efficacy but HAL2PIM had less EPS at end point. Both HAL groups and
      RIS6PBO showed equal improvement in psychopathology at endpoint, indicating HAL
      2mg/day is effective to treat an acute exacerbation in chronic schizophrenia
      patients. In conclusion, a sub-effective RIS dose combined with PIM to enhance 5
      HT(2A) receptor blockade provided faster onset of action, and at endpoint, equal
      efficacy and better safety, compared to standard dose RIS. These results support
      the conclusion that 5-HT(2A) receptor blockade is a key component of the action
      of some atypical APDs and can reduce EPS due to a typical APD.

PMID- 22954755
TI  - Effects of omega-3 dietary supplement in prevention of positive, negative and
      cognitive symptoms: a study in adolescent rats with ketamine-induced model of
      schizophrenia.
AB  - Omega-3 has shown efficacy to prevent schizophrenia conversion in ultra-high risk
      population. We evaluated the efficacy of omega-3 in preventing ketamine-induced
      effects in an animal model of schizophrenia and its effect on brain-derived
      neurotrophic factor (BDNF). Omega-3 or vehicle was administered in Wistar male
      rats, both groups at the 30th day of life for 15days. Each group was split in two
      to receive along the following 7days ketamine or saline. Locomotor and
      exploratory activities, memory test and social interaction between pairs were
      evaluated at the 52nd day of life. Prefrontal-cortex, hippocampus and striatum
      tissues were extracted right after behavioral tasks for mRNA BDNF expression
      analysis. Bloods for serum BDNF were withdrawn 24h after the end of behavioral
      tasks. Locomotive was increased in ketamine-treated group compared to control,
      omega-3 and ketamine plus omega-3 groups. Ketamine group had fewer contacts and
      interaction compared to other groups. Working memory and short and long-term
      memories were significantly impaired in ketamine group compared to others. Serum
      BDNF levels were significantly higher in ketamine plus omega-3 group. There was
      no difference between groups in prefrontal-cortex, hippocampus and striatum for
      mRNA BDNF expression. Administration of omega-3 in adolescent rats prevents
      positive, negative and cognitive symptoms in a ketamine animal model of
      schizophrenia. Whether these findings are consequence of BDNF increase it is
      unclear. However, this study gives compelling evidence for larger clinical trials
      to confirm the use of omega-3 to prevent schizophrenia and for studies to
      reinforce the beneficial role of omega-3 in brain protection.

PMID- 22954756
TI  - Telaprevir: pharmacokinetics and drug interactions.
AB  - Telaprevir is an inhibitor of the HCV NS3/4A protease. When used in combination
      with pegylated interferon and ribavirin, telaprevir has demonstrated a
      substantial increase in sustained virological response compared with pegylated
      interferon and ribavirin used alone. Telaprevir has good oral bioavailability,
      which is enhanced when administered with food. Telaprevir is extensively
      metabolized and primarily eliminated via faeces. No dose adjustment of telaprevir
      is needed in patients with mild to severe renal impairment or mild liver
      impairment. Telaprevir is a substrate and inhibitor of cytochrome P450 3A and P
      glycoprotein and, thus, might interact with coadministered drugs that affect or
      are affected by these metabolic/transport pathways. This article reviews the
      pharmacokinetic and drug interaction profile of telaprevir.

PMID- 22954757
TI  - System to classify cause of deaths in HIV-positive persons:  time to harmonize.

PMID- 22954758
TI  - HIV protease inhibitors in combination with boceprevir:  are drug-drug
      interactions the same for all patients?

PMID- 22954759
TI  - Limitations of proposed novel trial design.

PMID- 22954760
TI  - Novel clinical trial designs for the development of new antiretroviral agents.

PMID- 22954761
TI  - Acute congestive heart failure and death secondary to itraconazole therapy.

PMID- 22954762
TI  - What's clinically relevant and new in pediatric and adolescent gynecology?

PMID- 22954763
TI  - Development of stem cell therapy for stress urinary incontinence.
AB  - PURPOSE OF REVIEW: In recent years, stem cell therapy has been investigated as a
      promising approach for the treatment of stress urinary incontinence (SUI). This
      article reviews the biology of stem cells and their applications as a cell-based
      treatment for SUI. The current status and future direction of this forefront
      research in urinary incontinence are also examined. RECENT FINDINGS: During the
      past decade, adult stem cells have been studied as a potential cell-based
      approach for the treatment of SUI. The results of current preclinical and
      clinical studies are presented. These studies demonstrated the improvement in
      histologic and functional outcomes with stem cell therapies for SUI. Adult stem
      cells may augment sphincter regeneration and also release trophic factors,
      promoting vessel and nerve integration into the generated tissues. So far, the
      findings of the clinical trials are less impressive than the results obtained
      with animal studies. SUMMARY: Although stem cell therapy holds much promise for
      SUI, the clinical applications in patients have been slow to materialize. This
      challenge, together with the currently limited data on basic science studies and
      clinical trials, will undoubtedly stimulate new investigations in the near
      future.

PMID- 22954764
TI  - Asymptomatic microscopic hematuria.
AB  - PURPOSE OF REVIEW: To examine the 2001 American Urological Association (AUA)
      recommendations for the evaluation of asymptomatic microscopic hematuria (AMH) in
      light of the most recent studies available. RECENT FINDINGS: AMH is a nonspecific
      marker of disease, but can also be found in healthy individuals. The research
      done seeks to better identify those patients who present with AMH and have a
      clinically significant disease. These investigations include epidemiological
      studies that describe populations at risk, define clinically significant
      hematuria, and provide long-term follow-up to patients with AMH. Authors have
      examined the validity and effectiveness of recommended and nonrecommended tests
      for AMH in different populations. Finally, several studies looked into what
      workup, if any, patients with AMH were receiving in the community. SUMMARY: The
      evaluation of female patients with AMH needs to be tailored to the individual
      patient's presentation and risk factors. This evaluation should be timely and
      always include testing of both upper and lower urinary tract. After a complete
      negative assessment, no further follow-up is needed.

PMID- 22954765
TI  - Controversies in utilization of transvaginal mesh.
AB  - PURPOSE OF REVIEW: Due to technological advancements, transvaginal mesh use for
      prolapse and incontinence has exploded over the last decade with mixed results.
      Recent governmental guidelines have further increased the controversy regarding
      the risks and benefits of mesh use forcing clinicians to critically review the
      available data regarding transvaginal mesh use. RECENT FINDINGS: With the success
      of the transvaginal tape procedure introduced in 1995 and re-popularization of
      the abdominal sacrocolpopexy using synthetic mesh, pelvic surgeons began to feel
      more comfortable using mesh in urogynecologic procedures and increasingly adopted
      the use of transvaginal mesh for repair of pelvic prolapse with the hopes of
      creating better long-term results with minimal complications. With introduction
      of commercially available kits and widespread adoption of these procedures
      amongst pelvic surgeons and general gynecologists, there is increasing concern
      regarding related complications including mesh exposure, dyspareunia/pelvic pain,
      infection, and organ injury. This has resulted in recent reappraisal of vaginal
      mesh use, increased medicolegal risk, and withdrawal of selected products.
      SUMMARY: The data regarding transvaginal mesh use are controversial and
      incomplete. Its use is still in its infancy in terms of material development and
      clinical/scientific study, and clinicians should be careful and judicious in its
      use.

PMID- 22954766
TI  - Managing vaginal mesh exposure/erosions.
AB  - PURPOSE OF REVIEW: To review the known causes, presentation, and management of
      synthetic mesh exposure and other healing abnormalities associated with
      transvaginal implantation for pelvic organ prolapse. RECENT FINDINGS: The recent
      restriction of mesh used in urogynecology to type 1 monofilament/macroporous mesh
      has led to recognizable patterns of healing abnormality development. Excision of
      exposed or contracted mesh segments usually leads to symptom resolution. There
      are various surgical techniques recognized to reduce the risk of exposure
      development. Pain, when associated with mesh use, may be more challenging to
      manage and may persist in a small percentage of patients. Surgeons should be
      aware of recently recognized risk factors for exposure development and carefully
      select patients for mesh implantation based on risk:benefit assessment. SUMMARY:
      The use of synthetic mesh implanted transvaginally for urogynecologic indications
      is associated with recognized risks, including exposure (approximately 10%) and
      contraction which can usually be managed successfully with local estrogen, in
      office trimming, or surgical excision of the exposed or contracted segment.

PMID- 22954767
TI  - Current world literature.

PMID- 22954770
TI  - Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs
      external beam radiation therapy alone for prostate cancer.
AB  - PURPOSE: To evaluate the outcomes of patients treated for intermediate- and high
      risk prostate cancer with a single schedule of either external beam radiation
      therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone.
      METHODS AND MATERIALS: From 2001-2006, 344 patients received EBRT with HDRB boost
      for definitive treatment of intermediate- or high-risk prostate cancer. The
      prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3
      fractions. This cohort was compared to a contemporaneously treated cohort who
      received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three
      dimensional conformal EBRT was used. Matching was performed using a propensity
      score matching technique. High-risk patients constituted 41% of the matched
      cohorts. Five-year clinical and biochemical outcomes were analyzed. RESULTS:
      Initial significant differences in prognostic indicators between the unmatched
      treatment cohorts were rendered negligible after matching, providing a total of
      688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom
      from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%)
      and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively,
      equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction
      analyses showed no alteration in HDR efficacy when planned androgen deprivation
      therapy was administered (P=.95), but a strong trend toward reduced efficacy was
      shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral
      stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and
      HDRB, respectively (P<.0001). No differences in clinical outcomes were observed.
      CONCLUSIONS: This comparison of 2 individual contemporaneously treated HDRB and
      EBRT approaches showed improved freedom from biochemical progression with the HDR
      approach. The benefit was more pronounced in intermediate- risk patients but
      needs to be weighed against an increased risk of urethral toxicity.

PMID- 22954769
TI  - Leishmania parasites possess a platelet-activating factor acetylhydrolase
      important for virulence.
AB  - Leishmania parasites are intracellular protozoans capable of salvaging and
      remodeling lipids from the host. To understand the role of lipid metabolism in
      Leishmania virulence, it is necessary to characterize the enzymes involved in the
      uptake and turnover of phospholipids. This study focuses on a putative
      phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in
      Leishmania major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the
      hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of
      many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH
      is predominantly localized in the ER. While wild type L. major parasites are able
      to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null
      mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the
      turnover of common glycerophospholipids such as phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF
      AH is not required for the growth of L. major parasites in culture, or the
      production of GPI-anchored virulence factors. Nonetheless, it does play a key
      role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated
      virulence in BALB/c mice. In conclusion, these data suggest that Leishmania
      parasites possess a functional PAF-AH and the degradation of PAF or PAF-like
      lipids is an important step in infection.

PMID- 22954771
TI  - Dose-effect relationships for adverse events after cranial radiation therapy in
      long-term childhood cancer survivors.
AB  - PURPOSE: To evaluate the prevalence and severity of clinical adverse events (AEs)
      and treatment-related risk factors in childhood cancer survivors treated with
      cranial radiation therapy (CRT), with the aim of assessing dose-effect
      relationships. METHODS AND MATERIALS: The retrospective study cohort consisted of
      1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT
      delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI),
      and as total body irradiation (TBI). Individual CRT doses were converted into the
      equivalent dose in 2-Gy fractions (EQD(2)). Survivors had received their
      diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A
      complete inventory of Common Terminology Criteria for Adverse Events grade 3.0
      AEs was available from our hospital-based late-effect follow-up program. We used
      multivariable logistic and Cox regression analyses to examine the EQD(2) in
      relation to the prevalence and severity of AEs, correcting for sex, age at
      diagnosis, follow-up time, and the treatment-related risk factors surgery and
      chemotherapy. RESULTS: There was a high prevalence of AEs in the CRT group; over
      80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both
      representing significant increases in number of AEs compared with survivors not
      treated with CRT. Additionally, the proportion of severe, life-threatening, or
      disabling AEs was significantly higher in the CRT group. The most frequent AEs
      were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using
      the EQD(2), we found significant dose-effect relationships for these and other
      AEs. CONCLUSION: Our results confirm that CRT increases the prevalence and
      severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect
      relationships with the cumulative EQD(2) instead of total physical dose connects
      the knowledge from radiation therapy and radiobiology with the clinical
      experience.

PMID- 22954772
TI  - Encapsulated curcumin results in prolonged curcumin activity in vitro and radical
      scavenging activity ex vivo on skin after UVB-irradiation.
AB  - The phytochemical curcumin possesses antioxidant activity; however, it becomes
      unstable after being exposed to light or heat or loses activity during storage.
      This is especially important when curcumin is applied to the skin within a
      cosmetic or pharmaceutical formulation, since sun exposure is unavoidable. This
      drawback can be directly addressed by encapsulation of curcumin in photo-stable
      nanospheres. Therefore, curcumin was encapsulated into nanoparticles consisting
      of ethyl cellulose and/or methyl cellulose. Nanoparticles were subjected to
      processing conditions commonly used in industry, for example, temperature and
      pressure and thus retained their morphology. Furthermore, sun exposure resulted
      in the protection of curcumin by nanoparticles, whereas non-encapsulated curcumin
      degraded completely. Determination of the radical protection factor resulted in
      similar antioxidant activity of encapsulated and non-encapsulated curcumin
      indicating that curcumin maintains its antioxidant activity. Application of
      lotions containing curcumin or curcumin nanoparticles to the skin and subsequent
      UVB-irradiation resulted in less radical formation compared to lotion application
      only. Moreover, radical formation was even less after nanoparticle application
      compared to free curcumin. Nanoencapsulation protects curcumin from photo
      degradation and can therefore prolong the antioxidant activity of curcumin.

PMID- 22954773
TI  - Assessing the ergonomic hazards for pile drivers.
AB  - OBJECTIVE: The study was conducted to assess the physical/ergonomic exposures
      that may lead to musculoskeletal injuries of Pile Drivers. PARTICIPANTS: Pile
      Drivers in the Greater Boston area. METHODS: A hierarchical taxonomy for pile
      driving work was developed with tasks and activities defined within each of seven
      main pile driving operations. Exposures were characterized for the pile driving
      work with the PATH (Posture, Activity, Tools, and Handling) method. Data on
      working posture were collected for three main body parts: legs, arm and trunk.
      RESULTS: A total of 8,301 observations were made on 29 Pile Drivers, on a total
      of 6 work sites. The lagging operation had the highest percentage of observations
      with non-neutral trunk (46.8%), and leg (41.0%) postures, as well as one of the
      lowest percentages for working on stable ground (9.0%) as observed during the
      lagging operation. The bracing operation had the lowest percentage for working on
      stable ground (0.3%). The slurry wall operation also had a low percentage of work
      on stable ground (6.0%). Compared to the awkward trunk and leg postures, the arm
      postures were less frequently observed as being awkward or non-neutral.
      CONCLUSION: The results indicate of significant exposures that could lead to
      musculoskeletal injuries of the back and legs for the Pile Drivers. The unstable
      ground conditions seemed to be one of the main concerns for this job.

PMID- 22954782
TI  - G801A polymorphism of human stromal cell-derived factor 1 gene raises no
      susceptibility to neoplastic lesions of uterine cervix.
AB  - OBJECTIVE: This study aimed to investigate the association of stromal cell
      derived factor 1 (SDF-1) gene polymorphisms with the neoplastic lesions of
      uterine cervix in Mid-Taiwan women. MATERIALS AND METHODS: Four hundred ninety
      eight blood samples were collected from 161 patients with neoplasia of uterine
      cervix, including 76 cancer patients, 61 patients with high-grade dysplasia, and
      24 with low-grade dysplasia, and 337 healthy controls who lived in Mid-Taiwan.
      Polymorphism of the SDF-1 gene was examined using polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: For SDF-1 gene polymorphisms,
      the wild-type homozygous alleles (G/G) yielded 100- and 193-bp products, the
      heterozygous alleles (G/A) yielded 100-, 193- and 293-bp products, whereas the
      mutated-type homozygous alleles (A/A) yielded a 293-bp product. We found no
      significant difference in genotypes or alleles distribution of SDF-1
      polymorphisms between patients with cervical neoplasia and healthy women (P =
      0.530). Compared with the homozygous GG subgroup, GA and AA subgroups do not
      increase the risk of cervical neoplasia. CONCLUSIONS: Although the expression of
      SDF-1 was reported to be significantly increased in cervical carcinogenesis in
      previous studies, our results, however, show that SDF-1 gene polymorphism could
      not be considered as a factor related to an increased susceptibility to cervical
      neoplasia.

PMID- 22954783
TI  - Comparison of morbidity and survival between primary and interval cytoreductive
      surgery in patients after modified posterior pelvic exenteration for advanced
      ovarian cancer.
AB  - OBJECTIVE: Surgical management of advanced ovarian cancer often requires low
      modified posterior pelvic exenteration (MPE) to achieved complete resection. The
      aim of this study was to evaluate the morbidity of MPE at the time of primary
      cytoreductive surgery (PCS) and interval cytoreductive surgery (ICS) after
      neoadjuvant chemotherapy. MATERIALS AND METHODS: From 2001 to 2009, 63 patients
      underwent MPE for advanced ovarian cancer. We analyzed and compared surgical
      characteristics and postoperative courses between PCS and ICS. RESULTS: Modified
      posterior pelvic exenteration was performed during PCS for 50 patients (79%) and
      during ICS for 13 patients (21%). Complete cytoreduction was achieved in 80% of
      patients (84% in the PCS group and 69% in the ICS group; ns). There was no
      significant difference between the PCS and ICS groups in the type and the rate of
      standards or radical surgical procedures. Patients with ICS had a shorter length
      of stay in the intensive care unit (0.9 vs 2.7 days; P = 0.009), but there was no
      difference in the total length of hospitalization (P = 0.94). The global rate of
      postoperative complications was 76%. No differences were found between the 2
      groups in digestive or extradigestive complications, iterative surgery, or
      interventional radiology procedures. The median overall survival was 49.4 months
      in the PCS group and 27.1 months in the ICS group (P = 0.27), and the median
      progression-free survival time in both groups was 20 months. CONCLUSIONS: There
      was no difference in the occurrence of postoperative complications between PCS
      and ICS, especially in morbidity related to MPE. The specific morbidity of this
      surgical procedure remained low compared with the overall morbidity in cases of
      extensive surgery.

PMID- 22954784
TI  - Management and prognosis of borderline ovarian Brenner tumors.
AB  - OBJECTIVE: The borderline ovarian Brenner tumor (BOBT) of the ovary is a rare
      tumor, and fewer than 25 cases have been reported in the literature. The aim of
      this study was to determine the prognosis of a series of BOBT collected in 2
      reference centers. METHODS: A retrospective review of patients with BOBT treated
      or referred to our institutions. A centralized histological review by a reference
      pathologist and data on the clinical characteristics, management, and outcomes of
      patients were required for inclusion. RESULTS: Ten patients were identified
      between 2000 and 2010. The median age of patients was 69 years (range, 52-84
      years). Eight patients had pure BOBT and 2 had mixed histotype (mucinous and
      Brenner tumor). All patients had unilateral tumor and a stage I disease. No case
      of stromal microinvasion or intraepithelial carcinoma was observed. Among 5
      patients with data on the follow-up, 1 lethal recurrence (50 months after initial
      surgery) was observed (the first reported in the literature). CONCLUSIONS: During
      the management of BOBT, peritoneal staging surgery is not required because all
      patients reported in the present series (and all but one in the literature) had
      stage I disease. One recurrence had occurred in this retrospective series.
      Nevertheless, among 35 cases (including those in the present study) reported in
      the literature with outcomes, this tumor carries a good prognosis. The power of
      this conclusion is, however, limited because of the relatively small number of
      patients studied (but this is a rare entity) and the short follow-up period.

PMID- 22954785
TI  - Prognostic significance of rising serum CA-125 levels within the normal range in
      patients with epithelial ovarian, primary peritoneal, and tubal cancers, who,
      after initial treatment, had a complete clinical response.
AB  - OBJECTIVE: This study aimed to assess the ability of 3 criteria of rising CA-125
      levels within the reference range to predict recurrence in patients with ovarian,
      primary peritoneal, and tubal carcinomas after complete clinical response to
      initial treatment. MATERIAL AND METHODS: Included were patients diagnosed during
      1998 to 2008 who fulfilled the following criteria: CA-125 levels of 35 U/mL or
      greater at diagnosis and recurrence, full primary treatment with a complete
      clinical and radiographic response, follow-up according to schedule, and at least
      2 CA-125 results within the reference range during follow-up. Three criteria of
      rising CA-125 values within the reference range were used for the prediction of
      recurrence: (1) an absolute increase of 5 U/mL or higher from the nadir value at
      completion of chemotherapy, (2) early signal of progressive disease criterion,
      and (3) a rise to an absolute level of 20 U/mL or greater. RESULTS: Of 82
      patients who satisfied study inclusion criteria, 58 (70.7%) had disease
      recurrence. Early signal of progressive disease and a rise to an absolute level
      of 20 U/mL or greater were highly statistically significant predictors of disease
      recurrence (odds ratio, 12.62 [95% confidence interval, 2.71-58.7], P = 0.0012;
      and odds ratio, 6.7 [95% confidence interval, 2.18-20.54], P = 0.001,
      respectively) and preceded recurrence by a median of 3 and 3.3 months,
      respectively. CONCLUSIONS: Our data indicate that the early signal of progressive
      disease criterion and a single rise to an absolute level of 20 U/mL or greater
      within reference limits are highly predictive of clinical recurrence, although
      the latter is simpler to use. However, whether this is of practical clinical
      value remains to be proven.

PMID- 22954786
TI  - p300/CBP acetyl transferases interact with and acetylate the nucleotide excision
      repair factor XPG.
AB  - Nucleotide excision repair (NER) is an important DNA repair mechanism through
      which cells remove bulky DNA lesions. Following DNA damage, the histone
      acetyltransferase (HAT) p300 (also referred to as lysine acetyltransferase or
      KAT) is known to associate with proliferating cell nuclear antigen (PCNA), a
      master regulator of DNA replication and repair processes. This interaction, which
      results in HAT inhibition, may be dissociated by the cell cycle inhibitor
      p21(CDKN1A), thereby restoring p300 activity; however, the role of this protein
      interplay is still unclear. Here, we report that silencing p300 or its homolog
      CREB-binding protein (CBP) by RNA interference (RNAi) significantly reduces DNA
      repair synthesis in human fibroblasts. In addition, we determined whether p300
      and CBP may associate with and acetylate specific NER factors such as XPG, the 3'
      endonuclease that is involved in the incision/excision step and is known to
      interact with PCNA. Our results show that p300 and CBP interact with XPG, which
      has been found to be acetylated in vivo. XPG is acetylated by p300 in vitro, and
      this reaction is inhibited by PCNA. Knocking down both p300/CBP by RNAi or by
      chemical inhibition with curcumin greatly reduced XPG acetylation, and a
      concomitant accumulation of the protein at DNA damage sites was observed. The
      ability of p21 to bind PCNA was found to regulate the interaction between p300
      and XPG, and an abnormal accumulation of XPG at DNA damage sites was also found
      in p21(-/-) fibroblasts. These results indicate an additional function of
      p300/CBP in NER through the acetylation of XPG protein in a PCNA-p21 dependent
      manner.

PMID- 22954787
TI  - Ovine amniotic epithelial cells: in vitro characterization and transplantation
      into equine superficial digital flexor tendon spontaneous defects.
AB  - In vitro expanded and frosted ovine amniotic epithelial cells (oAECs) were
      evaluated for their phenotype, stemness and attitude to differentiate into
      tenocytes. Fifteen horses with acute tendon lesions were treated with one
      intralesional injection of oAECs. Tendon recovery under controlled training was
      monitored. In vitro expanded oAECs showed a constant proliferative ability, a
      conserved phenotype and stable expression profile of stemness markers.
      Differentiation into tenocytes was also regularly documented. US controls showed
      the infilling of the defect and early good alignment of the fibers and 12 horses
      resumed their previous activity. Histological and immunohistochemical
      examinations in an explanted tendon demonstrated the low immunogenicity of oAECs
      that were able to survive in the healing site. In addition, oAECs supported the
      regenerative process producing ovine collagen type I amongst the equine collagen
      fibers. Considering our results, oAECs can be proposed as a new approach for the
      treatment of spontaneous equine tendon injuries.

PMID- 22954788
TI  - In-vivo efficacy of toltrazuril on experimentally induced Toxoplasma gondii
      tissue cysts in lambs: a novel strategy for prevention of human exposure to meat
      borne toxoplasmosis.
AB  - The aim of the present study was to investigate in vivo efficacy of toltrazuril
      on Toxoplasma gondii tissue cysts following induction of chronic toxoplasmosis in
      4-week-old lambs (n=27) by inoculation of 1*10(5) T. gondii ME 49 strain oocysts
      (day 0). Beginning at the 15th day after inoculation, lambs in Group T20 and
      Group T40 were given toltrazuril orally 2 times, once every week (Baycox 5%,
      Bayer Animal Health) at a dose of 20 mg/kg and 40 mg/kg, respectively. Positive
      control (PC) lambs were not given any therapy, and 2 clinically healthy non
      infected lambs were used as negative controls (Group NC). Two out of 9 lambs in
      PC group (oocyst inoculated but non-treated) were killed on toltrazuril treatment
      days (day 15 and 22) to evaluate the tissue cyst presence in their muscles. On
      day 90, the remaining 25 lambs were necropsied, and samples from the brain and 11
      different muscle groups were collected. The tissues were examined for the
      presence of tissue cysts by histopathology, immunohistochemistry, nested-PCR and
      percoll gradient centrifugation. Anti-T. gondii antibodies were screened by IFAT
      throughout the experiment. The increased T. gondii seropositivity beginning from
      the 15th day of inoculation remained steady at Day 45 and Day 90 in Groups PC
      while it was significantly lower at Day 90 in toltrazuril receiving groups. In
      toltrazuril treated groups, histopathological findings included degenerative
      changes in the cyst wall, complete macrophage invasion to the cysts, and
      reduction or removal of the cysts in toto. Four out of 9 lambs (44.4%) in both
      toltrazuril treated group (Group T20 and T40) did not contain tissue cyst in any
      examined tissues while all positive control animals had T. gondii tissue cysts at
      least in one muscle group. The toltrazuril treatment efficacy on the cyst
      presence was determined as 44.4%. The number of the cysts in the musculature was
      significantly different between non-treated and toltrazuril treated lambs
      (X(2)=6.613; p=0.037). For the total number of cysts, the positive control lambs
      had higher number of cysts compared to both toltrazuril treated lambs (T20 and
      T40) (X(2)=5.629; p=0.018 and X(2)=5.629; p=0.018, respectively) while there were
      no differences between Group T20 and Group T40 (X(2)=0.000; p=1.000). According
      to PCR results, the brain and M. semitendinosus were positive in all 7 control
      lambs while 12 out of 18 lambs were positive in toltrazuril treated lambs. In
      conclusion, the results are promising as the toltrazuril treated lambs had
      markedly less parasite counts compared to those of untreated lambs. Further
      research should be conducted to reveal if toltrazuril treatment in sheep could be
      used as a strategy to minimize the cyst exposure of humans through consumption of
      raw or undercooked mutton.

PMID- 22954789
TI  - Application of KRL test to assess total antioxidant activity in pigs: sensitivity
      to dietary antioxidants.
AB  - The application of Kit Radicaux Libres (KRL) test to assess total blood
      antioxidant activity in pigs was evaluated. The KRL has been validated and is
      widely used in humans for assessing the effectiveness of natural or
      pharmaceutical treatments, and in vitro to evaluate the antioxidant activities of
      natural or synthetic antioxidants. In this study the sensitivity of the KRL test
      in assessing the effectiveness of dietary antioxidant supplementation (vitamin E
      and plant extract) was evaluated in two different phases of pig breeding. The
      first trial, in post-weaned piglets (40 piglets/group) fed dietary vitamin E
      supplementation for 60 days, indicated that there was a higher total antioxidant
      activity (P=0.032) of whole blood and of red blood cells (P=0.001) than for
      control pigs. The second trial indicated that long-term supplementation of water
      soluble plant extract (20 pigs/group) from the leaves of Verbenaceae (Lippia
      spp.) tended (P=0.091) to increase antioxidant activity in the whole blood of
      treated, rather than control pigs. These results indicate that the KRL might be
      recommended as one of efficient means for evaluating antioxidant activity of
      dietary ingredients fed to pigs.

PMID- 22954790
TI  - Downbeat nystagmus due to a paramedian medullary lesion.
AB  - Cell groups of the paramedian tract, which are located in the paramedian region
      of the lower brainstem, are eye-movement-related neurons that project to the
      cerebellar flocculus. Their inactivation produces downbeat nystagmus, which
      resembles eye movement disorders resulting from lesions of the cerebellar
      flocculus in animal experiments. Therefore, paramedian tract cells are assumed to
      fulfill an important function in ocular movement control, such as gaze-holding
      and maintaining vestibular balance. This paper presents a 50-year-old female who
      manifested downbeat nystagmus due to damage to the paramedian tract cells caused
      by a localized ischemic lesion in the medulla oblongata. We found that a
      paramedian medullary lesion-induced nystagmus, similar to that observed following
      floccular lesions, clearly indicates that a subgroup of paramedian tract cells
      projecting to the flocculus was impaired. This finding has important implications
      in considering a brainstem-cerebellar feedback loop involved in vestibulo
      oculomotor controls, such as vestibular balance. Although there have been a few
      reports of downbeat nystagmus caused by lesions in the midline region of the
      lower brainstem, to our knowledge none report the occurrence of nystagmus due to
      a strictly localized medullar lesion, such as the one described here.

PMID- 22954791
TI  - Painful cervical dystonia triggered by the extension wire of a deep brain
      stimulator.
AB  - Deep brain stimulation (DBS) can be complicated by adverse events, which are
      generally classified as surgical-hardware or stimulation-related. Here we report
      the onset of a painful cervical dystonia probably triggered by the extension wire
      of a subthalamic nucleus (STN)-DBS device in a woman suffering from advanced
      Parkinson's disease (PD). Two months after implantation of the STN-DBS device,
      our patient developed a painful cervical dystonia, which was not responsive to
      neurostimulation or to medication. No sign of infections or fibrosis was
      detected. A patch test with the components of the device was performed, revealing
      no hypersensibility. The patient was referred back to surgery to reposition the
      pulse generator in the contralateral subclavian region. A deeper channeling of
      the wire extensions produced a complete remission of the painful dystonia.

PMID- 22954792
TI  - Herniation of an enlarged middle cerebral artery through a temporal bone defect
      in association with an arteriovenous malformation.
AB  - We present a previously undescribed variant of the middle cerebral artery (MCA)
      protruding through a defect in the temporal bone, associated with a large
      arteriovenous malformation (AVM). The patient, a 59-year-old male, presented with
      a large right frontoparietal AVM with feeding aneurysms and a recent haemorrhage.
      Preoperative imaging demonstrated a tortuous right MCA feeder abutting the
      anterosuperior temporal bone in the region of the pterion. An associated temporal
      bone defect was visible. The patient underwent a pterional craniotomy for
      surgical clipping of aneurysms associated with the AVM. On reflection of the
      temporalis muscle, the MCA branch was transected as it coursed through a defect
      in the temporal bone. This patient demonstrates that the MCA may deviate from its
      usual anatomy and herniate through a defect in the skull. Because a pterional
      craniotomy is such a common surgical approach, knowledge and anticipation of such
      anatomic variants are essential to avoid catastrophic vascular injury during
      surgery.

PMID- 22954794
TI  - Repropedia: a reproductive lexicon to fill the gap in reproductive terminology.

PMID- 22954793
TI  - FZD1 regulates cumulus expansion genes and is required for normal female
      fertility in mice.
AB  - WNT4 is required for normal ovarian follicle development and female fertility in
      mice, but how its signal is transduced remains unknown. Fzd1 encodes a WNT
      receptor whose expression is markedly induced in both mural granulosa cells and
      cumulus cells during the preovulatory period, in a manner similar to Wnt4. To
      study the physiological roles of FZD1 in ovarian physiology and to determine
      whether it serves as receptor for WNT4, Fzd1-null mice were created by gene
      targeting. Whereas rare Fzd1(-/-) females were sterile because of uterine
      fibrosis and ovarian tubulostromal hyperplasia, most were subfertile, producing
      ~1 fewer pup per litter on average relative to controls. Unlike WNT4-deficient
      mice, ovaries from Fzd1(-/-) mice had normal weights, numbers of follicles,
      steroid hormone production, and WNT4 target gene expression levels. Microarray
      analyses of granulosa cells from periovulatory follicles revealed few genes whose
      expression was altered in Fzd1(-/-) mice. However, gene expression analyses of
      cumulus-oocyte complexes (COCs) revealed a blunted response of both oocyte (Zp3,
      Dppa3, Nlrp5, and Bmp15) and cumulus (Btc, Ptgs2, Sema3a, Ptx3, Il6, Nts, Alcam,
      and Cspg2) genes to the ovulatory signal, whereas the expression of these genes
      was not altered in WNT4-deficient COCs from Wnt4(tm1.1Boer/tm1.1Boer);Tg (CYP19A1
      cre)1Jri mice. Despite altered gene expression, cumulus expansion appeared normal
      in Fzd1(-/-) COCs both in vitro and in vivo. Together, these results indicate
      that Fzd1 is required for normal female fertility and may act in part to regulate
      oocyte maturation and cumulus cell function, but it is unlikely to function as
      the sole ovarian WNT4 receptor.

PMID- 22954795
TI  - Combined inhibitory effects of pyruvate and low temperature on postovulatory
      aging of mouse oocytes.
AB  - This study tested the hypothesis that oocyte aging could be prevented for a
      longer time by reducing the culture temperature while supplementing the culture
      medium with more pyruvate. Newly ovulated mouse oocytes were cultured at various
      temperatures for various times in HCZB medium (Kimura and Yanagimachi, Biol
      Reprod 1995; 52:709-720) containing various concentrations of pyruvate before
      examining for aging parameters and developmental potential. The increase in
      susceptibility to activating stimuli was efficiently prevented when oocytes were
      cultured in HCZB with 10.27 mM pyruvate at 37 degrees C for 6 h, 25 degrees C for
      24 h, 15 degrees C for 96 h, and 5 degrees C for 48 h. Satisfactory blastocyst
      development of both parthenotes and fertilized zygotes was achieved after oocyte
      culture in HCZB containing 10.27 mM pyruvate at 37 degrees C for 6 h, 25 degrees
      C for 24 h, 15 degrees C for 36 h, and 5 degrees C for 24 h. Transfer of two-cell
      embryos or blastocysts showed no difference between newly ovulated control
      oocytes and oocytes cultured at 15 degrees C for 36 h in either term pregnancy,
      live young per pregnant recipient, live young/transferred embryos, or birth
      weight of young. Oocytes with impaired developmental potential after culture at
      15 degrees C for 96 h and at 5 degrees C for 48 h showed unrecoverable decreases
      in the content of glutathione, the glutathione/oxidized glutathione ratio, the
      BCL2 content, and in the numbers of oocytes with normal spindles and cortical
      granule distribution, suggesting induction of oxidative stress, which caused
      oocyte apoptosis and cytoskeleton alterations by downregulating BCL2. Because
      oocytes cultured at 15 degrees C for 36 h were activated or fertilized after a 6
      h recovery culture, aging of ovulated mouse oocytes has been successfully
      prevented for 42 h without impairing their developmental potential.

PMID- 22954796
TI  - Imaging of vascular development in early mouse decidua and its association with
      leukocytes and trophoblasts.
AB  - In species with endometrial decidualization and hemochorial placentation (humans,
      mice, and others), leukocytes localize to early implant sites and contribute to
      decidual angiogenesis, spiral arterial remodeling, and trophoblast invasion.
      Relationships between leukocytes, trophoblasts, and the decidual vasculature are
      not fully defined. Early C57BL/6J implant sites were analyzed by flow cytometry
      to define leukocyte subsets and by whole-mount immunohistochemistry to visualize
      relationships between leukocytes, decidual vessels, and trophoblasts. Ptprc(+)
      (CD45(+)) cells increased in decidua between Gestational Day (GD) 5.5 and GD 9.5.
      Uterine natural killer (uNK) cells that showed dynamic expression of Cd (CD) 69,
      an activating receptor, and Klrg1 (KLRG1), an inhibitory receptor, localized
      mesometrially and were the dominant CD45(+) cells between GD 5.5 and GD 7.5. At
      GD 8.5, immature monocytes that occurred throughout decidua exceeded uNK cells
      numerically and many leukocytes acquired irregular shapes, and leukocyte
      leukocyte conjugates became frequent. Vessels were morphologically heterogeneous
      and regionally unique. Migrating trophoblasts were first observed at GD 6.5 and,
      at GD 9.5, breached endothelium, entered vascular lumens, and appeared to occlude
      some vessels, as described for human spiral arteries. No leukocyte-trophoblast
      conjugates were detected. Whole-mount staining gave unparalleled decidual
      vascular detail and cell-specific positional information. Its application across
      murine models of pregnancy disturbances should significantly advance our
      understanding of the maternal-fetal interface.

PMID- 22954798
TI  - Differential effects of tenofovir/emtricitabine and abacavir/lamivudine on human
      leukocyte recruitment.
AB  - BACKGROUND: The association of abacavir (ABC) with cardiovascular disease has led
      to HIV treatment guidelines favouring the combination of tenofovir/emtricitabine
      (TDF/FTC) over that of ABC/lamivudine (ABC/3TC). We have analysed the effects of
      plasma-relevant concentrations of TDF, FTC, ABC and 3TC, individually and in
      clinically employed combinations, on human leukocyte accumulation. The effects of
      ABC, 3TC, TDF and FTC on the expression of adhesion molecules were also
      evaluated. METHODS: Interactions between human leukocytes - specifically
      peripheral blood polymorphonuclear or mononuclear cells - and human umbilical
      vein endothelial cells were evaluated in a flow chamber reproducing in vivo
      conditions. The expression of adhesion molecules was analysed by flow cytometry.
      RESULTS: Concentrations of TDF, FTC or 3TC mimicking those in the plasma of
      patients did not have any effect on human leukocyte-endothelial cell
      interactions, while contrasting results were obtained with ABC. This distinct
      pattern was reproduced when the drugs were administered in combination; namely,
      ABC/3TC had a significant influence on rolling and adhesion while TDF/FTC did
      not. However, the effects produced by ABC alone did not differ when it was
      combined with 3TC, which suggests the former drug was responsible for the effects
      observed. ABC, 3TC, TDF and FTC did not modify the expression of endothelial
      adhesion molecules. Conversely, only ABC enhanced the expression of leukocyte
      CD11b/CD18 in neutrophils and monocytes. CONCLUSIONS: Our results provide
      evidence that the combination TDF/FTC has a better vascular profile than ABC/3TC.

PMID- 22954799
TI  - Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells.
AB  - Eryptosis, the suicidal erythrocyte death, leads to cell shrinkage and cell
      membrane scrambling with phosphatidylserine exposure at the cell surface.
      Eryptotic erythrocytes adhere to the vascular wall by binding of
      phosphatidylserine to the CXC chemokine ligand 16 (CXCL16). Stimulators of
      eryptosis include increased cytosolic Ca(2+) activity, energy depletion, and
      activation of ceramide-producing sphingomyelinase. The present study explored
      whether sphingomyelinase triggers erythrocyte adhesion to endothelial cells. To
      this end, human erythrocytes were exposed for 6 h to bacterial sphingomyelinase
      (1-10 mU/ml) and phosphatidylserine exposure was estimated from fluorescent
      annexin-V-binding, cell volume from forward scatter in FACS-analysis, erythrocyte
      adhesion to human umbilical vein endothelial cells (HUVEC) from trapping of
      labeled erythrocytes in a flow chamber under flow conditions at arterial shear
      rates, and CXCL16 protein abundance utilizing Western blotting and FACS analysis
      of fluorescent antibody binding. As a result, sphingomyelinase (>=1 mU/ml)
      triggered cell shrinkage, phosphatidylserine exposure and erythrocyte adhesion to
      HUVEC, effects blunted by Ca(2+) removal. Adhesion was significantly blunted by
      phosphatidylserine-coating annexin-V (5 MUl/ml), following addition of
      neutralizing antibodies against endothelial CXCL16 (4 MUg/ml) and following
      silencing of the CXCL16 gene with small interfering RNA. Pretreatment of HUVEC
      with sphingomyelinase upregulated CXCL16 protein abundance. Six hours
      pretreatment of HUVEC with sphingomyelinase (10 mU/ml) or C6-ceramide (50 MUM)
      augmented erythrocyte adhesion following a 30-min treatment with Ca(2+) ionophore
      ionomycin (1 MUM) or following energy depletion by 48-h glucose removal. Thus
      exposure to sphingomyelinase or C6-ceramide triggers eryptosis followed by
      phosphatidylserine- and CXCL16-sensitive adhesion of eryptotic erythrocytes to
      HUVEC.

PMID- 22954800
TI  - Genetic polymorphism in Leishmania (Viannia) braziliensis detected in mucosal
      leishmaniasis of HIV-infected and non-HIV-infected patients.
AB  - The genetic polymorphism of Leishmania (Viannia) braziliensis detected in cases
      of mucosal leishmaniasis (ML) from HIV-infected and non HIV-infected patients was
      evaluated. Nine samples from three HIV-infected patients and five samples from
      five non HIV-infected patients were analysed by polymerase chain reaction (PCR),
      low-stringency single-specific primer PCR (LSSP-PCR) and phenetic analysis. The
      presence of L. (V.) braziliensis DNA was detected in all samples by specific PCR
      assay. The intraspecific polymorphism of the variable region of L. (V.)
      braziliensis kDNA minicircles was investigated by LSSP-PCR. Phenetic analysis
      grouped the genetic profiles into two distinct clusters, which discriminated
      between samples obtained from HIV-infected and non HIV-infected patients. In two
      HIV-infected patients, identical genetic profiles were detected in lesions
      biopsied at different times after the treatment of the initial lesion.
      Interestingly, genetically divergent profiles were detected in the cutaneous and
      mucosal lesions of the same HIV-infected patient collected at the same time. This
      is the first work comparing genetic polymorphism of L. (V.) braziliensis in cases
      of mucosal leishmaniasis from HIV-infected and non HIV-infected patients.

PMID- 22954801
TI  - Comparison of toxicity and transcriptomic profiles in a diatom exposed to oil,
      dispersants, dispersed oil.
AB  - Dispersants are commonly used to mitigate the impact of oil spills, however, the
      ecological cost associated with their use is uncertain. The toxicity of weathered
      oil, dispersed weathered oil, and the hydrocarbon-based dispersant Slickgone
      NS((r)), to the diatom Phaeodactylum tricornutum has been examined using
      standardized toxicity tests. The assumption that most toxicity occurs via
      narcosis was tested by measuring membrane damage in diatoms after exposure to one
      of the petroleum products. The mode of toxic action was determined using
      microarray-based gene expression profiling in diatoms after exposure to one of
      the petroleum products. The diatoms were found to be much more sensitive to
      dispersants than to the water accommodated fraction (WAF), and more sensitive to
      the chemically enhanced WAF (CEWAF) than to either the WAF itself or the
      dispersants. Exposure to dispersants and CEWAF caused membrane damage, while
      exposure to WAF did not. The gene expression profiles resulting from exposure to
      all three petroleum mixtures were highly similar, suggesting a similar mode of
      action for these compounds. The observed toxicity bore no relationship to PAH
      concentrations in the water column or to total petroleum hydrocarbon (TPH),
      suggesting that an undescribed component of the oil was causing toxicity. Taken
      together, these results suggest that the use of dispersants to clean up oil
      spills will dramatically increase the oil toxicity to diatoms, and may have
      implications for ecological processes such as the timing of blooms necessary for
      recruitment.

PMID- 22954802
TI  - CD4(+)CD25(+)Foxp3(+)IFNgamma(+) Treg are immunosuppressive in vitro and increase
      with intensity of the alloresponse in pretransplant MLC.
AB  - IFNgamma-producing CD3(+)CD4(+)CD25(+)Foxp3(+) induced Treg are more frequently
      detectable in patients with good than in patients with impaired long-term kidney
      graft function. We investigated the in-vitro function of separated
      CD3(+)CD4(+)CD25(+)Foxp3(+)IFNgamma(+) PBL that were induced by phorbol-12
      myristate-13-acetate(PMA)/Ionomycin or alloantigenic stimulation. Additionally,
      we studied iTreg induction and cell proliferation in MLC with pretransplant
      obtained PBL. CD4(+)CD25(+)IFNgamma(+) PBL separated from PMA/Ionomycin
      stimulated PBL of healthy controls inhibited secondary cell cultures of
      autologous PBL. Furthermore, CD4(+)CD25(+)IFNgamma(+) PBL separated from primary
      MLC and added to secondary MLC suppressed allogeneic T-cell activation in
      secondary MLC unspecifically, irrespective of the stimulator cell. However, the
      strongest suppression was observed in specific MLC. Patients with poor long-term
      graft outcome were able to form IFNgamma(+) iTreg in pretransplant MLC. Eight
      patients with a serum creatinine level ranging from 0.9 to 14 mg/dl 18-29 years
      posttransplant were studied. In MLC with pretransplant obtained recipient and
      donor cells, strong IFNgamma(+) iTreg (p=0.007) and strong blast induction
      (p=0.047) were associated with impaired long-term graft outcome. Long-term graft
      outcome was not associated with cell proliferation and iTreg induction in
      unspecific MLC with third-party cells as stimulator. The data indicate that
      patients with impaired long-term graft outcome are able to form high numbers of
      IFNgamma(+) iTreg in specific pretransplant MLC. Quantity of induced IFNgamma(+)
      iTreg depends on the strength of the alloresponse and both parameters are
      inversely associated with long-term graft outcome.

PMID- 22954803
TI  - [Severe acute caffeine intoxication. A report of two cases with different
      outcomes].

PMID- 22954804
TI  - Different mechanisms of hepatitis C virus RNA polymerase activation by
      cyclophilin A and B in vitro.
AB  - BACKGROUND: Cyclophilins (CyPs) are cellular proteins that are essential to
      hepatitis C virus (HCV) replication. Since cyclosporine A was discovered to
      inhibit HCV infection, the CyP pathway contributing to HCV replication is a
      potential attractive stratagem for controlling HCV infection. Among them, CyPA is
      accepted to interact with HCV nonstructural protein (NS) 5A, although interaction
      of CyPB and NS5B, an RNA-dependent RNA polymerase (RdRp), was proposed first.
      METHODS: CyPA, CyPB, and HCV RdRp were expressed in bacteria and purified using
      combination column chromatography. HCV RdRp activity was analyzed in vitro with
      purified CyPA and CyPB. RESULTS: CyPA at a high concentration (50* higher than
      that of RdRp) but not at low concentration activated HCV RdRp. CyPB had an
      allosteric effect on genotype 1b RdRp activation. CyPB showed genotype
      specificity and activated genotype 1b and J6CF (2a) RdRps but not genotype 1a or
      JFH1 (2a) RdRps. CyPA activated RdRps of genotypes 1a, 1b, and 2a. CyPB may also
      support HCV genotype 1b replication within the infected cells, although its
      knockdown effect on HCV 1b replicon activity was controversial in earlier
      reports. CONCLUSIONS: CyPA activated HCV RdRp at the early stages of
      transcription, including template RNA binding. CyPB also activated genotype 1b
      RdRp. However, their activation mechanisms are different. GENERAL SIGNIFICANCE:
      These data suggest that both CyPA and CyPB are excellent targets for the
      treatment of HCV 1b, which shows the greatest resistance to interferon and
      ribavirin combination therapy.

PMID- 22954805
TI  - Contribution of caveolin-1 to ventricular nitric oxide in age-related adaptation
      to hypovolemic state.
AB  - Our previous results have shown that hypovolemic state induced by acute
      hemorrhage in young anesthetized rats triggers heterogeneous and dynamic nitric
      oxide synthase (NOS) activation, modulating the cardiovascular response.
      Involvement of the nitric oxide pathway is both isoform-specific and time
      dependent. The aim of the present study was to investigate changes in activity
      and protein levels of the different NOS forms, changes in the abundance of
      caveolin-1 during hypovolemic state and caveolin-1/eNOS association using young
      and middle-aged rats. Therefore, we studied (i) changes in NOS activity and
      protein levels and (ii) caveolin-1 abundance, as well as its association with
      endothelial NOS (eNOS) in ventricles from young and middle-aged rats during
      hypovolemic state. We used 2-month (young) and 12-month (middle-aged) old male
      Sprague-Dawley rats. Animals were divided into two groups (n=14/group): (a) sham;
      (b) hemorrhaged animals (20% blood loss). With advancing age, we observed an
      increase in ventricle NOS activity accompanied by a decrease in eNOS and caveolin
      1 protein levels, but increased inducible NOS (iNOS). We also observed that aging
      is associated with caveolin-1 dissociation from eNOS. Myocardia from young and
      middle-aged rats subjected to hemorrhage-induced hypovolemia exhibited an
      increase in NOS activity and protein levels with a reduction in caveolin-1
      abundance, accompanied by a greater dissociation between eNOS and its regulatory
      protein. Further, an increase in iNOS protein levels after blood loss was
      observed only in middle-aged rats. Our evidence suggests that aging and acute
      hemorrhage contribute to the development of upregulation in NOS activity. Our
      findings demonstrate that specific expression patterns of ventricular NOS
      isoforms, alterations in the amount of caveolin-1 and caveolin-1/eNOS interaction
      are involved in aged-related adjustment to hypovolemic state.

PMID- 22954806
TI  - Characterization of alunite supergroup minerals by Raman spectroscopy.
AB  - Raman spectroscopy has been used to study the molecular structure of different
      natural minerals of the alunite supergroup (AB(3)(XO(4))(2)(OH)(6)), with A=K(+),
      Na(+), Ca(2+), Sr(2+), Ba(2+), B=Al(3+), Fe(3+) and X=S(6+), P(5+). The influence
      of the ions, in A-, B- and X-sites, is highlighted in the Raman spectra by
      variations in the position of certain vibrations and is discussed in association
      with published crystallographic data in order to describe the observed
      differences. It was found that A-site substitutions are characterized by
      wavenumber shifts of the vibrations involving hydroxyl groups. The positions of
      these vibrational bands vary linearly with the ionic radius of the ions in this
      site. B-site substitutions induce shifts of all bands due to structural
      modifications that lead to differences in the chemical environment around the
      hydroxyl and XO(4) groups and changes in B-O bond lengths. A correlation showed
      that these shifts correlate well with the ionic radii of the B-ions. The spectra
      of compounds containing both sulfate and phosphate groups are described by
      numerous vibration bands caused by a complex elemental composition and a symmetry
      change of the XO(4) groups. This study has also made it possible to generalize
      substitution effects on the wavenumbers of several vibrations and show that Raman
      spectroscopy could be a powerful tool for identifying and distinguishing minerals
      of the alunite supergroup.

PMID- 22954807
TI  - Raman and IR spectroscopic studies of fenamates--conformational differences in
      polymorphs of flufenamic acid, mefenamic acid and tolfenamic acid.
AB  - Solid-state Raman and IR spectra of two polymorphic forms of each of three
      fenamates (flufenamic acid, mefenamic acid and tolfenamic acid) display subtle
      but highly reproducible differences. Many of these spectral differences can be
      ascribed to different conformations of these molecules, involving two of four
      possible orientations of one substituted benzene ring with respect to the other.
      Interpretation of the vibrational spectra in terms of conformational differences
      has been facilitated by DFT calculations at the B3LYP/cc-pVDZ level for each
      conformer. The calculated spectra are compared with the experimental spectra in
      order to identify the conformers present in two polymorphic forms in each case,
      and detailed band assignments are obtained from the DFT calculations.

PMID- 22954808
TI  - Molecular structure, vibrational spectra, NLO and NBO analysis of bis(8-oxy-1
      methylquinolinium) hydroiodide.
AB  - In this paper, quantum chemistry calculations of geometric parameters, harmonic
      vibrational wavenumbers, molecular frontier orbital energies (HOMO and LUMO) and
      the electronic properties of bis(8-oxy-1-methylquinolinium) hydroiodide
      ([(C(10)H(9)NO)(2)H(+)].I(-)) have been performed by using Gaussian 09 program.
      The structural and spectroscopic data of the molecule in the ground state have
      been calculated by using Hartree-Fock (HF) and density functional method
      (DFT/B3LYP) with the LanL2DZ basis set. For the spectra predicted, a potential
      energy distribution (PED) is calculated. The (1)H and (13)C nuclear magnetic
      resonance (NMR) chemical shifts values of bis(8-oxy-1-methylquinolinium)
      hydroiodide molecule have been calculated by the gage including atomic orbital
      (GIAO) method. Furthermore, molecular electrostatic potential maps (MEP),
      Mulliken charges and the natural bonding orbital (NBO) analysis of the compound
      have been calculated by the HF and B3LYP/Lanl2DZ methods.

PMID- 22954809
TI  - Eu-doped Mg-Al layered double hydroxide as a responsive fluorescent material and
      its interaction with glutamic acid.
AB  - The paper describes a study on the fluorescence of a Eu-doped Mg-Al layered
      double hydroxide (Eu-doped LDH) response to glutamic acid (Glu). Various
      characterizations (UV-Vis transmittance, TG-DTA and IR-spectrum) indicated that
      there is an interaction between the Eu-doped LDH and Glu. Fluorescent study was
      found that the red emissions resulted from (5)D(0)-(7)F(J) transition (J=1, 2) of
      Eu(3+) markedly decreased, while the blue emission at 440 nm contributed to Glu
      shifted to low energy after the addition of Glu to the Eu-doped LDH. The
      fluorescent changes may be relevant to the hydrogen-bond interaction between the
      Eu-doped LDH and Glu, and the mechanism of the interaction between Eu-doped LDH
      and Glu was discussed.

PMID- 22954810
TI  - Characterization and catalytic activity of gold nanoparticles synthesized using
      ayurvedic arishtams.
AB  - The development of new synthesis methods for monodispersed nanocrystals using
      cheap and nontoxic chemicals, environmentally benign solvents and renewable
      materials remains a challenge to the scientific community. The present work
      reports a new green method for the synthesis of gold nanoparticles. Four
      different ayurvedic arishtams are used for the reduction of Au(3+) to Au
      nanoparticles. This method is simple, efficient, economic and nontoxic. Gold
      nanoparticles having different sizes in the range from 15 to 23 nm could be
      obtained. The nanoparticles have been characterized by UV-Visible spectroscopy,
      transmission electron microscopy (TEM), X-ray diffraction (XRD) and FTIR
      analysis. The high crystallinity of nanoparticles is evident from bright circular
      spots in the SAED pattern and peaks in the XRD pattern. The synthesized gold
      nanoparticles show good catalytic activity for the reduction of 4-nitrophenol to
      4-aminophenol by excess NaBH(4). The synthesized nanoparticles are found to
      exhibit size dependent catalytic property, the smaller nanoparticles showing
      faster activity.

PMID- 22954811
TI  - Spectrophotometric and thermodynamic studies of the interactions of 4-carboxyl
      2,6-dinitrophenylazohydroxynaphthalenes with bovine serum albumin.
AB  - The intermolecular interaction occurring between bovine serum albumin and 4
      carboxyl-2,6-dinitrophenylazohydroxynaphthalene in aqueous media has been studied
      spectrophotometrically at different temperatures including body temperature.
      Evidence for the formation of new molecular complexes was established by
      hypsochromic and hypochromic shifts of the spectra of dye-BSA complexes compared
      to the spectra of unbound dyes. One congener (AZ-02) gave a minor peak
      characteristic of charge-transfer complexation. The binding constants of the four
      monoazo dyes were investigated and found to vary according to the dye structure
      and temperature of investigation. AZ-01 and -04 combined with BSA at
      approximately 1:1 mol ratio while the other two congeners with additional proton
      donors gave greater than this mole ratio. Thermodynamic considerations
      established that the dyes utilized the various forms of binding modes; hydrogen
      bonding, hydrophobic bonding, van der Waals and AZ-03 was particularly involved
      in electrostatic interactions giving positive entropy change for a small enthalpy
      change. The observed properties were correlated with the genotoxicity potentials
      of the monoazo dyes. The results obtained should prove beneficial in designing
      other molecules in this category of chemical class.

PMID- 22954812
TI  - Are bipolar disorders underdiagnosed in patients with depressive episodes?
      Results of the multicenter BRIDGE screening study in Germany.
AB  - BACKGROUND: Recent reports indicate that the prevalence of bipolar disorder (BD)
      in patients with an acute major depressive episode might be higher than
      previously thought. We aimed to study systematically all patients who sought
      therapy for major depressive episode (MDE) within the BRIDGE study in Germany,
      reporting on an increased number (increased from 2 in the international BRIDGE
      report to 5) of different diagnostic algorithms. METHODS: A total of 252 patients
      with acute MDE (DSM-IV confirmed) were examined for the existence of BD (a)
      according to DSM-IV criteria, (b) according to modified DSM-IV criteria (without
      the exclusion criterion of 'mania not induced by substances/antidepressants'),
      (c) according to a Bipolarity Specifier Algorithm which expands the DSM-IV
      criteria, (d) according to HCL-32R (Hypomania-Checklist-32R), and (e) according
      to a criteria-free physician's diagnosis. RESULTS: The five different diagnostic
      approaches yielded immensely variable prevalences for BD: (a) 11.6; (b) 24.8%;
      (c) 40.6%; (d) 58.7; e) 18.4% with only partial overlap between diagnoses
      according to the physician's diagnosis or HCL-32R with diagnoses according to the
      three DSM-based algorithms. CONCLUSIONS: The diagnosis of BD in patients with MDE
      depends strongly on the method and criteria employed. The considerable difference
      between criteria-free physician's diagnosis and the remaining algorithms indicate
      the usefulness of criteria lists within the everyday clinical setting.
      LIMITATIONS: Diagnoses based on DSM were only made with checklists. The diagnoses
      of (hypo-) manic episodes in the patient history were not systematically
      verifiable by indirect anamnesis.

PMID- 22954814
TI  - Current world literature.

PMID- 22954813
TI  - Subtotal/near-total treatment of vestibular schwannomas.
AB  - PURPOSE OF REVIEW: The review evaluates current literature on subtotal and near
      total resection of vestibular schwannomas. RECENT FINDINGS: Recent findings
      suggest that subtotal and near-total resection of vestibular schwannomas can be
      performed to improve facial nerve outcomes. This is particularly true for large
      tumors. Whereas postoperative facial nerve function is likely improved by partial
      resection, recurrence rates are higher, although they vary depending on the
      extent of resection. If a tumor remnant grows following partial resection, the
      small-volume remnant can be treated with stereotactic radiation with good tumor
      control rates. SUMMARY: Subtotal and near-total resection of vestibular
      schwannomas is a reasonable surgical paradigm for vestibular schwannomas which
      cannot be completely removed without injuring the facial nerve. Whereas facial
      nerve outcomes are more favorable in partial resections, the risk of recurrence
      increases and is proportional to the volume of residual tumor.

PMID- 22954817
TI  - Guided internet treatment for anxiety disorders. As effective as face-to-face
      therapies?
AB  - INTRODUCTION: Guided Internet-delivered treatments were developed in the late
      1990s and have since been tested in numerous controlled trials. While promising,
      there are yet few direct comparisons between Internet treatments and traditional
      face-to-face treatments. The aim of the present study is to present an overview
      of the evidence in the field of anxiety disorders. METHOD: Studies were located,
      including unpublished trials from our research group in Sweden. RESULTS: Results
      of direct comparative trials on panic disorder (n=3) and social anxiety disorder
      (n=3) show equivalent outcomes. One study on specific phobia did not show
      equivalent outcomes with an advantage for face-to-face treatment. However, a
      systematic review by Cuijpers et al. (2010) found equivalent outcomes across
      several self-help formats, suggesting that guided self-help overall can be as
      affective as face-to-face treatments. CONCLUSION: Overall, there are still few
      large-scale trials and statistical power is often limited. A preliminary
      conclusion is that guided Internet treatment can be as effective as face-to-face
      treatments, but there is a need to investigate moderators and mediators of the
      outcome.

PMID- 22954818
TI  - Inter-reality in the evaluation and treatment of psychological stress disorders:
      the INTERSTRESS project.
AB  - "Psychological stress" occurs when an individual perceives that environmental
      demands tax or exceed his or her adaptive capacity. According to the Cochrane
      Database of Systematic Reviews, the best validated approach covering both stress
      management and stress treatment is the Cognitive Behavioral (CBT) approach. CBT
      has undergone a very large number of trials in research contexts. However, it has
      been less efficacious in clinical contexts and it has become obvious that CBT has
      some failings when applied in general practice. INTERSTRESS is a EU-funded
      project that aims to design, develop and test an advanced ICT-based solution for
      the assessment and treatment of psychological stress that is able to address
      three critical limitations of CBT: a) the therapist is less relevant than the
      specific protocol used. b) the protocol is not customized to the specific
      characteristics of the patient; c) the focus of the therapy is more on the top
      down model of change (from cognitions to emotions) than on the bottom-up (from
      emotions to cognitions). To reach this goal the INTERSTRESS project applies an
      innovative paradigm for e-health - Interreality - that integrates assessment and
      treatment within a hybrid environment, bridging physical and virtual worlds. On
      one side, the patient is continuously assessed in the virtual and real worlds by
      tracking the behavioral and emotional status in the context of challenging tasks
      (customization of the therapy according to the characteristics of the patient).
      On the other side, feedback is continuously provided to improve both the
      appraisal and the coping skills of the patient through a conditioned association
      between effective performance state and task execution behaviors (improvement of
      self efficacy). Within this conceptual framework, it is possible to set up and
      test psychological treatments that could be extended also beyond the traditional
      research and clinical setting by using more and more emerging mobile technology
      to deliver real-time interventions during daily activities and ecological
      contexts.

PMID- 22954819
TI  - Modeling the social networking experience objectifying the subjective.
AB  - This study aimed at measuring objectively the experience of using social network
      sites (SNSs). At this aim, a model of experience has been defined, focusing on
      three main aspects of time-space continuum of individuals' states: physiological
      arousal, emotional valence, and attentional resources. At this purpose we
      developed a new approach to assess such an experience. The main idea is to
      consider arousal, valence and attention to track the users' experience collecting
      psychophysiological indexes at predefined period (for example each 10 seconds) to
      build an empirical model based on these data. Once we got the empirical curve we
      can fit these data using mathematical models.

PMID- 22954820
TI  - The use of virtual reality in the treatment of eating disorders.
AB  - A high percentage of patients with eating disorders (ED) respond to treatments
      such as cognitive-behavioural therapy. However, some patients do not progress
      significantly with these treatments, or suffer relapses. The incorporation of new
      technologies may help to increase the efficacy of standard treatments. Virtual
      reality has been successfully used to treat body image disturbances in ED
      patients and seems a suitable technology for cue exposure therapy in this
      setting. We review the published literature and discuss the results.

PMID- 22954821
TI  - Lessons learned from the development of technological support for PTSD
      prevention: a review.
AB  - This review describes the state-of-the-art technologies that support mental
      resilience training for PTSD prevention. It characterizes four current systems
      across training approaches; seeks insights via interviews with the system
      developers; and extracts from these a set of essential guidelines for future
      developers. The guidelines include four distinct project-limiting factors, which
      were found to constrain the reviewed developments. These were Culture,
      Effectiveness, Engineering, and Resource constraints.This research is novel in
      reviewing technologies for PTSD prevention as opposed to treatment, and in
      analyzing from the perspective of system development and design issues.

PMID- 22954822
TI  - Virtual worlds and avatars as the new frontier of telehealth care.
AB  - We are entering a new age where people routinely visit, inhabit, play in and
      learn within virtual worlds (VWs). One in eight people worldwide are VW
      participants, according to the latest 2011 figures from KZERO [1]. VWs are also
      emerging as a new and advanced form of telehealth care delivery. In addition to
      existing telehealth care advantages; VWs feature three powerful affordances that
      can benefit a wide range of physical and psychological issues. First, the highly
      social nature of VWs encourages social networking and the formation of essential
      support groups. Secondly, the type of spaces that have been proven in the
      physical world to promote psychological health and well-being can be virtually
      recreated. Finally, research suggests that embodied avatar representation within
      VWs can affect users psychologically and physically. These three aspects of VWs
      can be leveraged for enhanced patient-client interactions, spaces that promote
      healing and positive responses, and avatar activities that transfer real benefits
      from the virtual to the physical world. This paper explains the mounting evidence
      behind these claims and provides examples of VWs as an innovative and compelling
      form of telehealth care destined to become commonplace in the future.

PMID- 22954823
TI  - Adapting computerized treatments into traditional psychotherapy for depression.
AB  - Recent developments in technology have helped to improve the process of
      psychotherapy. Unfortunately, many therapists lack the computer skills or
      financial resources needed for the newest technology. Nonetheless, even basic
      advances in technology may help to improve the treatment of depression. METHOD:
      The literature is reviewed for journal articles on the treatment of depression
      published during the past seven years in which treatments have been guided by
      technology. RESULTS: Six novel findings are summarized that may be helpful even
      when the therapist lacks skill or resources for advanced technology. 1) The
      efficient assessment of depression can be facilitated by technology, whether
      using standardized measures or simple daily ratings of mood. 2) Technology tools
      can be used to send semi-automated daily reminders to help clients develop more
      adaptive habits in thoughts or actions. 3) Depressed clients can begin to
      confront their negative view of self, often triggered by some form of loss,
      failure, or rejection, whether real, imagined, or anticipated. 4) Clients can
      confront their problems through therapeutic dialogue, whether conducted in
      person, over the telephone, or via video conference. 5) Clients can use writing
      assignments to identify, label, explore and express their thoughts and feelings.
      These writing assignments can be conducted via paper, email, or internet forms.
      6) Clients value rapport with a therapist, and this bond seems important to
      ensure participation and adherence with treatment. CONCLUSION: Even low-tech
      therapists can strengthen the treatment of depression using basic technology
      tools to replace, extend, or supplement traditional sessions. However, it is
      important to protect the rapport needed for sustained participation in therapy.

PMID- 22954824
TI  - What is Positive Technology and its impact on cyberpsychology.
AB  - The goal of this paper is to introduce and describe the "Positive Technology"
      approach - the scientific and applied approach to the use of technology for
      improving the quality of our personal experience through its structuring,
      augmentation and/or replacement - as a way of framing a suitable object of study
      in the field of cyberpsychology and human-computer interaction. Specifically, we
      suggest that it is possible to use technology to influence three specific
      features of our experience - affective quality, engagement/actualization and
      connectedness - that serve to promote adaptive behaviors and positive
      functioning. In this framework, positive technologies are classified according to
      their effects on a specific feature of personal experience. More, for each level
      we have identified critical variables that can be manipulated to guide the design
      and development of positive technologies.

PMID- 22954825
TI  - Human computer confluence applied in healthcare and rehabilitation.
AB  - Human computer confluence (HCC) is an ambitious research program studying how the
      emerging symbiotic relation between humans and computing devices can enable
      radically new forms of sensing, perception, interaction, and understanding. It is
      an interdisciplinary field, bringing together researches from horizons as various
      as pervasive computing, bio-signals processing, neuroscience, electronics,
      robotics, virtual & augmented reality, and provides an amazing potential for
      applications in medicine and rehabilitation.

PMID- 22954826
TI  - A brief review of positive technology in Europe and the USA.
AB  - The aim of this paper is to demonstrate the potential of positive technology to
      productively and positively transform the mental health of European and American
      citizens in the modern era. This work will describe three aspects - hedonic,
      eudaimonic, and social/interpersonal - of these technologies. We approach them
      with guarded optimism, as all of them seek to improve our lives through various
      techniques. After exploring the relevant technologies, this piece will then
      examine the future for research within this domain.

PMID- 22954828
TI  - Promotion of emotional wellbeing in oncology inpatients using VR.
AB  - INTRODUCTION: In Psycho-oncology, VR has been utilized mainly to manage pain and
      distress associated to medical procedures and chemotherapy, with very few
      applications aimed at promotion of wellbeing in hospitalized patients.
      Considering this, it was implemented a psychological intervention that uses VR to
      induce positive emotions on adult oncology inpatients with the purpose of
      evaluating its utility to improve emotional wellbeing in this population. METHOD:
      Sample was composed of 33 patients (69.7% men, aged from 41 to 85 years old;
      X=62.1; SD=10.77). Intervention lasted 4 sessions of 30 minutes, along one week.
      In these sessions, two virtual environments designed to induce joy or relaxation
      were used. Symptoms of depression and anxiety (Hospital Anxiety and Depression
      Scale, HADS) and level of happiness (Fordyce Scale) were assessed before and
      after the VR intervention. Also, Visual Analogue Scales (VAS) were used to assess
      emotional state and physical discomfort before and after each session. RESULTS:
      There were significant improvements in distress and level of happiness after the
      VR intervention. Also, it was detected an increment in positive emotions and a
      decrease in negative emotions after sessions. CONCLUSIONS: Results emphasize the
      potential of VR as a positive technology that can be used to promote wellbeing
      during hospitalization, especially considering the shortness of the intervention
      and the advanced state of disease of the participants. Despite the encouraging of
      these results, it is necessary to confirm them in studies with larger samples and
      control groups.

PMID- 22954829
TI  - Mobilizing bystanders of cyberbullying: an exploratory study into behavioural
      determinants of defending the victim.
AB  - This study explores behavioural determinants of defending behaviour in
      cyberbullying incidents. Three focus groups were conducted with youngsters aged
      12-16 y. Major themes that were found as important behavioural determinants to
      defend the victim were a low moral disengagement, that the victim is an in-group
      member and that the bystander is popular. Bystanders preferred to handle
      cyberbullying offline and in person, and comforting the victim was considered
      more feasible than facing the bully. With a high peer acceptance of passive
      bystanding and lack of parental support for defending behaviour, youngsters do
      not receive much encouragement from their environment to exhibit defending
      behaviour towards victims. These preliminary results suggest befriending and peer
      support interventions hold promise, as well as environmental interventions with
      parents and teachers. These first results will need to be confirmed in more in
      depth analyses and in quantitative research.

PMID- 22954830
TI  - Influence of parental attitudes towards Internet use on the employment of online
      safety measures at home.
AB  - In this paper we present the results of a cross-sectional study of the entire
      adolescent student population aged 12-18 of the island of Kos and their parents,
      on Internet safety-related practices and attitudes towards the Internet. Total
      sample was 2017 students and 1214 parent responders. Research material included
      extended demographics and an Internet security questionnaire, the Internet
      Attitudes Scale (IAS) for parents and the Adolescent Computer Addiction Test
      (ACAT) for children and both parents. Both parents thus provided their views on
      their children's computer use and an estimate for their degree of computer
      addiction which was tested against their child's self-report. Results indicated
      that fathers and mothers who had negative views of the Internet, tended to
      encourage less their children to engage in online activities and worried more for
      the possibility that their child is addicted to computer use; their worries
      weren't correlated with their children's results. Parental views on the Internet
      had no effect on the level of security precautions they employed at home. Those
      parents who reported a low level of security knowledge and were unsure as to what
      their children were doing online, tended to consider their children more likely
      to be addicted to computer use; those views were confirmed by their children'
      self-reported results.

PMID- 22954831
TI  - Outcomes from a pilot study using computer-based rehabilitative tools in a
      military population.
AB  - Novel therapeutic approaches and outcome data are needed for cognitive
      rehabilitation for patients with a traumatic brain injury; computer-based
      programs may play a critical role in filling existing knowledge gaps. Brain
      fitness computer programs can complement existing therapies, maximize
      neuroplasticity, provide treatment beyond the clinic, and deliver objective
      efficacy data. However, these approaches have not been extensively studied in the
      military and traumatic brain injury population. Walter Reed National Military
      Medical Center established its Brain Fitness Center (BFC) in 2008 as an adjunct
      to traditional cognitive therapies for wounded warriors. The BFC offers
      commercially available "brain-training" products for military Service Members to
      use in a supportive, structured environment. Over 250 Service Members have
      utilized this therapeutic intervention. Each patient receives subjective
      assessments pre and post BFC participation including the Mayo-Portland
      Adaptability Inventory-4 (MPAI-4), the Neurobehavioral Symptom Inventory (NBSI),
      and the Satisfaction with Life Scale (SWLS). A review of the first 29 BFC
      participants, who finished initial and repeat measures, was completed to
      determine the effectiveness of the BFC program. Two of the three questionnaires
      of self-reported symptom change completed before and after participation in the
      BFC revealed a statistically significant reduction in symptom severity based on
      MPAI and NBSI total scores (p < .05). There were no significant differences in
      the SWLS score. Despite the typical limitations of a retrospective chart review,
      such as variation in treatment procedures, preliminary results reveal a trend
      towards improved self-reported cognitive and functional symptoms.

PMID- 22954832
TI  - Nicotine craving: ERPs correlates after VR exposure to smoking cues.
AB  - Even though it is diminishing in Europe, smoking is still a serious health
      problem. The craving of Nicotine is one of the hardest behaviours to tackle when
      a smoking cessation programme is implemented. Following on previous work [1],
      which aimed at evaluating the possibility of inducing smoking craving in smokers
      using a VR platform, the present study was devised to assess the role of craving
      in cognitive processing through event related potentials (ERP). From an initial
      sample of 89 university students (smokers and non-smokers), which was randomly
      exposed to VR smoking cues and VR non-smoking cue scenarios, a subsample of 13
      smokers and non-smokers was drawn. This subsample (M = 23.08; SD = 4.39), which
      had previously been immersed in the VR smoking cues environment, was presented to
      a rapid (1 sec) serial of smoking and neutral images. Data on brain activity was
      recorded through an EEG during this task to further estimate ERPs. When compared
      to non-smokers, smokers showed higher frontal activation when watching smoking
      related images.

PMID- 22954833
TI  - Reliability and validity of TIPS wireless ECG prototypes.
AB  - The aims of the present study are to examine the reliability and validity of the
      Heart Rate signal registered using two self-made wireless ECG systems, R-Tips and
      TipsShirt, and to compare them with another commercial ECG device typically used
      in psychophysiology studies. An ECG simulator was used to artificially generate
      signals corresponding to different cardiac frequencies. Results of the
      reliability study showed that the signal acquisition, signal processing and
      signal transmission were reliable and valid for R-Tips and TipsShirt.
      Consequently, these wireless ECG prototypes could be used for studies where the
      freedom of movements of the participants is fundamental without any loss of
      quality in the registered signals.

PMID- 22954834
TI  - Associations between facial emotion recognition, cognition and alexithymia in
      patients with schizophrenia: comparison of photographic and virtual reality
      presentations.
AB  - Emotion recognition is known to be impaired in schizophrenia patients. Although
      cognitive deficits and symptomatology have been associated with this impairment
      there are other patient characteristics, such as alexithymia, which have not been
      widely explored. Emotion recognition is normally assessed by means of
      photographs, although they do not reproduce the dynamism of human expressions.
      Our group has designed and validated a virtual reality (VR) task to assess and
      subsequently train schizophrenia patients. The present study uses this VR task to
      evaluate the impaired recognition of facial affect in patients with schizophrenia
      and to examine its association with cognitive deficit and the patients' inability
      to express feelings. Thirty clinically stabilized outpatients with a well
      established diagnosis of schizophrenia or schizoaffective disorder were assessed
      in neuropsychological, symptomatic and affective domains. They then performed the
      facial emotion recognition task. Statistical analyses revealed no significant
      differences between the two presentation conditions (photographs and VR) in terms
      of overall errors made. However, anger and fear were easier to recognize in VR
      than in photographs. Moreover, strong correlations were found between
      psychopathology and the errors made.

PMID- 22954835
TI  - Postural control of elderly: moving to predictable and unpredictable targets.
AB  - Impaired postural control with muscle weakness is an important predictor of falls
      within the elderly population.Particular daily activities that require weight
      shifting in order to be able to reach a specific target (a cup on a table)
      require continuous adjustments to keep the body's center of mass balanced. In the
      present study postural control was examined in healthy elderly and young subjects
      during a task in which subjects had to move the body's center of mass towards a
      virtual target on a screen that appeared at predictable and unpredictable
      locations. Postural control decreased with unpredictable targets, e.g. movement
      time was larger, trajectories more irregular. The results indicate that even
      though older individuals clearly benefitted from the early release of target
      location information, young individuals improved even more when target
      information became available.This indicates that the young were better able to
      use this information prospectively for executing the target directed movement
      quickly and accurately.

PMID- 22954836
TI  - Assessment of executive functions in patients with obsessive compulsive disorder
      by NeuroVR.
AB  - Executive functions are often impaired in obsessive-compulsive disorder (OCD). We
      used a Virtual Reality version of the Multiple Errand Test (VMET) - developed
      dusing the free NeuroVR software (http://www.neurovr.org) - to evaluate the
      executive functions in daily life in 10 OCD patients and 10 controls. It is
      performed in a shopping setting where there are items to be bought and
      information to be obtained. The execution time for the whole task was higher in
      patients with OCD compared to controls, suggesting that patients with OCD need
      more time in planning than controls. The same difference was found in the partial
      errors during the task. Furthermore, the mean rank for and for interpretation
      failures is higher for controls, while the values of divided attention and the of
      self correction seems to be lower in controls. We think that obsessive patients
      tend to work with greater diligence and observance of rules than controls. In
      conclusion, these results provide initial support for the feasibility of VMET as
      assessment tool of executive functions. Specifically, the significant correlation
      found between the VMET and the neuropsychological battery support the ecological
      validity of VMET as an instrument for the evaluation of executive functions in
      patients with OCD.

PMID- 22954838
TI  - Balance recovery through virtual stepping exercises using Kinect skeleton
      tracking: a follow-up study with chronic stroke patients.
AB  - Stroke patients often suffer from hemiparesis, which affects their balance
      condition and consequently their self-dependency and quality of life. Balance
      rehabilitation can be a long and tedious process. Virtual rehabilitation systems
      have been reported to provide therapeutic benefits to the balance recovery of
      stroke patients while increasing their motivation. This paper presents a follow
      up study involving chronic stroke patients to evaluate the clinical effectiveness
      of a virtual stepping exercise using skeleton tracking through a low-cost Kinect
      depth sensor.

PMID- 22954837
TI  - Exergaming for elderly: effects of different types of game feedback on
      performance of a balance task.
AB  - Balance training to improve postural control in elderly can contribute to the
      prevention of falls. Video games that require body movements have the potential
      to improve balance. However, research about the effects of type of visual
      feedback (i.e. the exergame) on the quality of movement and experienced workout
      intensity is scarce. In this study twelve healthy older and younger subjects
      performed anterior-posterior or mediolateral oscillations on a wobble board, in
      three conditions: no feedback, real-time visual feedback, and real-time visual
      feedback with a competitive game element. The Elderly moved slower, less
      accurately and more irregularly than younger people. Both feedback conditions
      ensured a more controlled movement technique on the wobble-board and increased
      experienced workout intensity. The participants enjoyed the attention demanding
      competitive game element, but this game did not improve balance performance more
      than interacting with a game that incorporated visual feedback. These results
      show the potential of exergames with visual feedback to enhance postural control.

PMID- 22954839
TI  - Effectiveness evaluation for short-term group pre-deployment VR computer-assisted
      stress inoculation training provided to Polish ISAF soldiers.
AB  - The goal of this study was to assess effectiveness of a short collective stress
      inoculation training (SIT) conducted according to the methodology of the Virtual
      Reality Medical Center of San Diego (Training of Physiological Control Exposure
      to Virtual Stressor while Maintaining Physiological Control). The results
      obtained indicate a short-term effectiveness of the training as a method of
      tension reduction. However, in the long-term perspective these results are
      ambiguous and they suggest a need of further research. In order to extend the
      analysis effects of temperamental factors on training effectiveness was
      presented.

PMID- 22954840
TI  - Using Virtual Week to assess prospective memory in younger and older adults.
AB  - Prospective memory (PM) is the ability to perform future intention. Older adults
      often present dysfunctions in PM tasks and investigating the nature of their
      difficulties have critical implication for their independent living. Virtual Week
      is a computer based program that simulate real week activities. Participants also
      performed executive functions tasks to investigate which abilities are involved
      in PM. Virtual Week has shown to be suitable instrument to evaluate PM
      performance with important implications on assessment and rehabilitation of PM
      dysfunctions.

PMID- 22954841
TI  - Smiling is fun: a Coping with Stress and Emotion Regulation Program.
AB  - Emotional disorders (Anxiety disorders and Mood disorders) are one of the most
      common health problems worldwide, and their economic costs are very high. People
      suffering from emotional disorders often use maladaptive emotion regulation
      strategies and have low coping behaviour that contributes to the presence of
      clinical symptoms. For this reason, it is important to develop strategies to
      monitor coping and promote emotion regulation in people exposed to high levels of
      stress. Information and Communication Technologies (ICT) can help us in this
      task. Recent systematic reviews of literature on evidence-based CBT treatments
      delivered via the Internet show that these approaches are effective. We have
      developed an intervention program ICT based: Coping with Stress and Emotion
      Regulation Program (Smiling is Fun), a self-applied program via the Internet.
      Smiling is Fun follows a transdiagnostic perspective, and it is based on CBT
      techniques. However, it also includes other psychological strategies to improve
      positive mood. The aim of the present work is to describe Smiling is Fun and the
      study designed to test its efficacy.

PMID- 22954842
TI  - The effectiveness of VR exposure therapy for PTSD in returning warfighters.
AB  - In the decade following the attack on the World Trade Center, over 2.3 million
      American military personnel were deployed to Iraq and Afghanistan. Lengthy tours
      of duty and multiple re-deployments were characteristic of these operations.
      Research findings demonstrate that prolonged exposure to combat increases the
      risk of developing posttraumatic stress disorder (PTSD). The current study was a
      randomized controlled clinical trial designed to assess the effectiveness of a
      novel intervention to treat combat-related PTSD in returning Operation Iraqi
      Freedom (OIF) and Operation Enduring Freedom (OEF) warfighters. A cognitive
      behavior treatment approach augmented with virtual reality exposure therapy (VRE)
      was developed, and administered for 10 treatment sessions over 5 weeks.
      Comparisons with a control group receiving minimal attention (MA) for 5 weeks
      revealed that the VRE group had significant reductions in the avoidance/numbing
      symptoms on the Clinician Administered PTSD Scale (CAPS). The VRE group also had
      significant reductions in guilt at post-treatment compared to the control group.

PMID- 22954843
TI  - Bottom-up and top-down influences of beliefs on emotional responses: fear of
      heights in a virtual environment.
AB  - According to cognitive approaches in emotion research, emotions hinge on beliefs
      that can be true or false. We suggest that emotionally relevant beliefs can be
      influenced bottom-up e.g. by the depth cues of a virtual environment or top-down
      e.g. by reappraisal strategies. Our research question is if bottom-up and top
      down processes influence the same belief structure or if different belief
      structures are responsible for bottom-up and top-down influences on emotions. To
      test these assumptions we exposed participants to a virtual environment that is
      able to elicit fear of heights and manipulated reappraisal for half of the
      participants. Moreover, we presented virtual scenes of heights in a monoscopic
      (less depth cues) and stereoscopic (more depth cues) mode in order to influence
      the confirmatory processes that are associated with beliefs. Subjective intensity
      of discomfort and the bending angle as a behavioural response were measured. We
      observed that although the depth cues and the reappraisal strategy were both
      effective in reducing the feeling of discomfort, reappraisal and the mode of
      presentation exert independent effects. Thus, beliefs that are triggered by
      bottom-up processes (depth cues) change emotions independent of the beliefs
      triggered by top-down processes (reappraisal).

PMID- 22954844
TI  - Implicit theory manipulations affecting efficacy of a smartphone application
      aiding speech therapy for Parkinson's patients.
AB  - A Smartphone speech-therapy application (STA) is being developed, intended for
      people with Parkinson's disease (PD) with reduced implicit volume cues. The STA
      offers visual volume feedback, addressing diminished auditory cues. Users are
      typically older adults, less familiar with new technology. Domain-specific
      implicit theories (ITs) have been shown to result in mastery or helpless
      behaviors. Studies manipulating participants' implicit theories of 'technology'
      (Study One), and 'ability to affect one's voice' (Study Two), were coordinated
      with iterative STA test-stages, using patients with PD with prior speech
      therapist referrals. Across studies, findings suggest it is possible to
      manipulate patients' ITs related to engaging with a Smartphone STA. This
      potentially impacts initial application approach and overall effort using a
      technology-based therapy.

PMID- 22954845
TI  - Mindfulness training online for stress reduction, a global measure.
AB  - According to the World Health Organization (WHO), stress-related chronic diseases
      are the main source of death in developed countries. During the last decade, e
      mental health, telepsychology or telepsychiatry interventions are showing its
      growing potential due to the gradual global adoption of the internet and mobile
      phone technologies. A significant number of studies have concluded that
      mindfulness helps to reduce physical and psychological symptoms of stress related
      to various health concerns and that it is a psychological skill that can be
      trained. The purpose of this online research study is to gather the participants'
      socio-demographics as well as stress and mindfulness data during an online
      mindfulness training program. Sustained attention and the state of mindfulness
      experienced in single meditation sessions are also tracked and stored.
      Correlational analysis yielded to a statistically significant relationship
      between high scores in stress and low scores in mindfulness facets (p < .001) and
      between state and trait aspects of mindfulness (p < .01).

PMID- 22954846
TI  - Psychophysiologic identification of subthreshold PTSD in combat veterans.
AB  - Posttraumatic stress disorder (PTSD) is linked with adverse health outcomes, and
      many military service members (SMs) are afflicted with it after they return from
      combat. Since many SMs have an initial honeymoon period characterized by limited
      symptoms before the onset of full-blown PTSD, the identification of independent
      predictors of PTSD upon return from deployment could facilitate early
      intervention. We measured psychophysiologic responses to stimuli including
      explosions in a Virtual Iraq/Afghanistan environment, as well as a fear
      potentiated startle paradigm, in a prospective cohort of SMs who did not meet
      criteria for PTSD and were within 2 months after return from deployment. We
      report marked psychophysiologic differences between those with (n = 29) and
      without (n = 30) subthreshold PTSD symptoms (PTSD Checklist score >= 28 vs. <
      28). We believe this is evidence that psychophysiologic measures can help to
      identify individuals at high risk for PTSD.

PMID- 22954847
TI  - On the comparison of VR-responses, as performance measures in prospective memory,
      with auditory P300 responses in MCI detection.
AB  - Patients with amnestic mild cognitive impairment are at high risk for developing
      Alzheimer's disease. Besides episodic memory dysfunction they show deficits in
      accessing contextual knowledge that further specifies a general spatial
      navigation task or an executive function (EF) virtual action planning. There has
      been only one previous work with virtual reality and the use of a virtual action
      planning supermarket for the diagnosis of mild cognitive impairment. The authors
      of that study examined the feasibility and the validity of the virtual action
      planning supermarket (VAP-S) for the diagnosis of patients with mild cognitive
      impairment (MCI) and found that the VAP-S is a viable tool to assess EF deficits.
      In our study we employed the in-house platform of virtual action planning museum
      (VAP-M) and a sample of 25 MCI and 25 controls, in order to investigate deficits
      in spatial navigation, prospective memory and executive function. In addition, we
      used the morphology of late components in event-related potential (ERP)
      responses, as a marker for cognitive dysfunction. The related measurements were
      fed to a common classification scheme facilitating the direct comparison of both
      approaches. Our results indicate that both the VAP-M and ERP averages were able
      to differentiate between healthy elders and patients with amnestic mild cognitive
      impairment and agree with the findings of the virtual action planning supermarket
      (VAP-S). The sensitivity (specificity) was 100% (98%) for the VAP-M data and
      87%(90%) for the ERP responses. Considering that ERPs have proven to advance the
      early detection and diagnosis of "presymptomatic AD", the suggested VAP-M
      platform appears as an appealing alternative.

PMID- 22954849
TI  - Tackling sensitive issues using a game-based environment: serious game for
      relationships and sex education (RSE).
AB  - Experiencing sexual coercion during adolescence can lead to adverse psychological
      and physical health outcomes for those affected. Eliminating such experiences is
      important for enhancing adolescent wellbeing, and the provision of good quality
      relationships and sex education (RSE) is needed. Engaging young people in
      sensitive subject matters in RSE can be challenging, and using Serious Gaming
      technology may support young people and educators in this process. This paper
      describes the use of Intervention mapping (IM) in the development of a serious
      game on the topic of sexual coercion for use in RSE. IM is a process that draws
      on stakeholder engagement and the theory and evidence base to support health
      improvement intervention planning. Serious game developers transformed the game
      concept 'flat plan' into an interactive gameshow. The game is teacher led and
      aims to engage students in game play and discussion around the issue of sexual
      coercion. The final product known as PR:EPARe (Positive Relationships:
      Eliminating Coercion and Pressure in Adolescent Relationships) is the subject of
      an ongoing cluster Randomised Controlled Trial (RCT) in local schools. Early data
      analysis shows improvements in psychological preparedness for dealing with sexual
      coercion against some change objectives. This work represents the first attempt
      to use IM in the development of a Serious Game and the use of Serious Gaming for
      RSE delivery. RCT work is ongoing and PR:EPARe will become part of local RSE
      delivery in the new school year. Plans for ensuring broader impact of the game
      are in development.

PMID- 22954850
TI  - Changing heartbeat perception to induce anxiety in virtual environments.
AB  - In this paper, we first propose a general technique to induce anxiety in virtual
      environments (VEs) which exploits auditory heartbeat perception and biofeedback.
      Then, we consider a VE that reproduces a real-world anxiety-inducing experience
      (being suddenly surrounded by smoke during a fire evacuation of a building), and
      we describe an experiment that contrasts 3 conditions: (i) an augmentation of the
      VE with a bar that indicates when the user's avatar gets hurt, (ii) an
      augmentation of the VE with the typical audio visual stimuli which are employed
      in violent videogames when the user's avatar gets hurt, (iii) introduction of the
      proposed biofeedback technique in the previous condition. We carry out an
      electrodermal analysis showing that the introduction of the proposed technique
      produces much higher physiological arousal in terms of skin conductance level
      (SCL) than the other two conditions. Subjective measures of users' state anxiety
      are consistent with the recorded physiological reactions.

PMID- 22954851
TI  - Quality of experience in real and virtual environments: some suggestions for the
      development of positive technologies.
AB  - What does one feel when one uses virtual reality? How does this experience differ
      from the experience associated with "real life" activities and situations? To
      answer these questions, we used the Experience Sampling Method (ESM), a procedure
      that allows researchers to investigate the daily fluctuations in the quality of
      experience through on-line self reports that participants fill out during daily
      life. The investigation consisted in one-week ESM observation (N = 42). During
      this week, participants underwent two virtual reality sessions: Immediately after
      the exposure to virtual environments, they were asked to complete a ESM report.
      For data analysis, experiential variables were aggregated into four dimensions:
      Mood, Engagement, Confidence, and Intrinsic Motivation Intrinsic Motivation.
      Findings showed that virtual experience is characterized by a specific
      configuration, which comprises significantly positive values for affective and
      cognitive components. In particular, positive scores of Mood suggest that
      participants perceived VR as an intrinsically pleasurable activity, while
      positive values of Engagement indicate that the use of VR and the experimental
      task provided valid opportunities for action and high skill investment.
      Furthermore, results showed that virtual experience is associated with Flow, a
      state of consciousness characterized by narrowed focus of attention, deep
      concentration, positive affect and intrinsic reward. Implications for VR research
      and practice are discussed.

PMID- 22954852
TI  - A system for automatic detection of momentary stress in naturalistic settings.
AB  - Prolonged exposure to stressful environments can lead to serious health problems.
      Therefore, measuring stress in daily life situations through non-invasive
      procedures has become a significant research challenge. In this paper, we
      describe a system for the automatic detection of momentary stress from behavioral
      and physiological measures collected through wearable sensors. The system's
      architecture consists of two key components: a) a mobile acquisition module; b)
      an analysis and decision module. The mobile acquisition module is a smartphone
      application coupled with a newly developed sensor platform (Personal
      Biomonitoring System, PBS). The PBS acquires behavioral (motion activity,
      posture) and physiological (hearth rate) variables, performs low-level, real-time
      signal preprocessing, and wirelessly communicates with the smartphone
      application, which in turn connects to a remote server for further signal
      processing and storage. The decision module is realized on a knowledge basis,
      using neural network and fuzzy logic algorithms able to combine as input the
      physiological and behavioral features extracted by the PBS and to classify the
      level of stress, after previous knowledge acquired during a training phase. The
      training is based on labeling of physiological and behavioral data through self
      reports of stress collected via the smartphone application. After training, the
      smartphone application can be configured to poll the stress analysis report at
      fixed time steps or at the request of the user. Preliminary testing of the system
      is ongoing.

PMID- 22954853
TI  - Immersive virtual environment for visuo-vestibular therapy: preliminary results.
AB  - The sense of equilibrium aggregates several interacting cues. On vestibular
      areflexic patients, vision plays a major role. We developed an immersive
      therapeutic platform, based on 3D opto-kinetic stimulation that enables to tune
      the difficulty of the balance task by managing the type of optic flow and its
      speed. The balance adjustments are recorded by a force plate, quantified by the
      length of the center of pressure trajectory and detection of disequilibrium
      corrections (leans, compensation step). Preliminary analysis shows that (i)
      patients report a strong immersion feeling in the motion flow, triggering intense
      motor response to "fight against fall"; (ii) the ANOVA factorial design shows a
      significant effect of flow speed, session number and gaze anchor impact. In
      conclusion, this study shows that 3D immersive stimulation removes essential
      limits of traditional opto-kinetic stimulators (limited 2D motions and remaining
      fixed background cues). Moreover, the immersive optic flow stimulation is an
      efficient tool to induce balance adaptive reactions in vestibular patients.
      Hence, such a platform appears to be a powerful therapeutic tool for training and
      relearning of balance control processes.

PMID- 22954854
TI  - Automatic mechanisms for measuring subjective unit of discomfort.
AB  - Current practice in Virtual Reality Exposure Therapy (VRET) is that therapists
      ask patients about their anxiety level by means of the Subjective Unit of
      Discomfort (SUD) scale. With an aim of developing a home-based VRET system, this
      measurement ideally should be done using speech technology. In a VRET system for
      social phobia with scripted avatar-patient dialogues, the timing of asking
      patients to give their SUD score becomes relevant. This study examined three
      timing mechanisms: (1) dialogue dependent (i.e. naturally in the flow of the
      dialogue); (2) speech dependent (i.e. when both patient and avatar are silent);
      and (3) context independent (i.e. randomly). Results of an experiment with non
      patients (n = 24) showed a significant effect for the timing mechanisms on the
      perceived dialogue flow, user preference, reported presence and user dialog
      replies. Overall, dialogue dependent timing mechanism seems superior followed by
      the speech dependent and context independent timing mechanism.

PMID- 22954855
TI  - Pulse oximeter based mobile biotelemetry application.
AB  - Quality and features of tele-homecare are improved by information and
      communication technologies. In this context, a pulse oximeter-based mobile
      biotelemetry application is developed. With this application, patients can
      measure own oxygen saturation and heart rate through Bluetooth pulse oximeter at
      home. Bluetooth virtual serial port protocol is used to send the test results
      from pulse oximeter to the smart phone. These data are converted into XML type
      and transmitted to remote web server database via smart phone. In transmission of
      data, GPRS, WLAN or 3G can be used. The rule based algorithm is used in the
      decision making process. By default, the threshold value of oxygen saturation is
      80; the heart rate threshold values are 40 and 150 respectively. If the patient's
      heart rate is out of the threshold values or the oxygen saturation is below the
      threshold value, an emergency SMS is sent to the doctor. By this way, the
      directing of an ambulance to the patient can be performed by doctor. The doctor
      for different patients can change these threshold values. The conversion of the
      result of the evaluated data to SMS XML template is done on the web server.
      Another important component of the application is web-based monitoring of pulse
      oximeter data. The web page provides access to of all patient data, so the
      doctors can follow their patients and send e-mail related to the evaluation of
      the disease. In addition, patients can follow own data on this page. Eight
      patients have become part of the procedure. It is believed that developed
      application will facilitate pulse oximeter-based measurement from anywhere and at
      anytime.

PMID- 22954856
TI  - Socially anxious people reveal more personal information with virtual counselors
      that talk about themselves using intimate human back stories.
AB  - In this paper, we describe our findings from research designed to explore the
      effect of virtual human counselors' self-disclosure using intimate human back
      stories on real human clients' social responses in psychological counseling
      sessions. To investigate this subject, we designed an experiment involving two
      conditions of the counselors' self-disclosure: human back stories and computer
      back stories. We then measured socially anxious users' verbal self-disclosure.
      The results demonstrated that highly anxious users revealed personal information
      more than less anxious users when they interacted with virtual counselors who
      disclosed intimate information about themselves using human back stories.
      Furthermore, we found that greater inclination toward facilitated self-disclosure
      from highly anxious users following interaction with virtual counselors who
      employed human back stories rather than computer back stories. In addition, a
      further analysis of socially anxious users' feelings of rapport demonstrated that
      virtual counselors elicited more rapport with highly anxious users than less
      anxious users when interacting with counselors who employed human back stories.
      This outcome was not found in the users' interactions with counselors who
      employed computer back stories.

PMID- 22954857
TI  - Use of Internet in an Italian clinical sample.
AB  - This study is aimed at evaluating Internet use in a psychiatric population. We
      used the UADI questionnaire to investigate the degree of addictive Internet use
      in our sample of patients affected by various psychiatric disorders. Several
      psychological and psychopathological variables related to internet use, have been
      assessed through the five dimensions of the UADI: dissociation (DIS), Impact on
      real life (IMP), Experimentation (EXP), Dependence (DEP), Escape (ESC).

PMID- 22954858
TI  - Online social networking and the experience of cyber-bullying.
AB  - Online social networking sites (SNS) are popular social tools used amongst
      adolescents and account for much of their daily internet activity. Recently,
      these sites have presented opportunities for youth to experience cyber-bullying.
      Often resulting in psychological distress, cyber-bullying is a common experience
      for many young people. Continual use of SNS signifies the importance of examining
      its links to cyber-bullying. This study examined the relationship between online
      social networking and the experience of cyber-bullying. A total of 400
      participants (Mage=14.31 years) completed an online survey which examined the
      perceived definitions and frequency of cyber-bullying. Users of SNS reported
      significantly higher frequencies of stranger contact compared to non-users.
      Spearman's rho correlations determined no significant relationship between daily
      time on SNS and the frequency of stranger contact. This suggests that ownership
      of a SNS profile may be a stronger predictor of some cyber-bullying experiences
      compared to time spent on these sites. Findings encourage continued research on
      the nature of internet activities used by young adolescents and the possible
      exposure to online victimization.

PMID- 22954859
TI  - Designing virtual audiences for fear of public speaking training - an observation
      study on realistic nonverbal behavior.
AB  - Virtual Reality technology offers great possibilities for Cognitive Behavioral
      Therapy of fear of public speaking: Clients can be exposed to virtual fear
      triggering stimuli (exposure) and are able to role-play in virtual environments,
      training social skills to overcome their fear. Usually, prototypical audience
      behavior (neutral, social and anti-social) serves as stimulus in virtual training
      sessions, although there is significant lack of theoretical basis on typical
      audience behavior. The study presented deals with the design of a realistic
      virtual presentation scenario. An audience (consisting of n=18 men and women) in
      an undergraduate seminar was observed during three frontal lecture sessions.
      Behavior frequency of four nonverbal dimensions (eye contact, facial expression,
      gesture, and posture) was rated by means of a quantitative content analysis.
      Results show audience behavior patterns which seem to be typical in frontal
      lecture contexts, like friendly and neutral face expressions. Additionally,
      combined and even synchronized behavioral patterns between participants who sit
      next to each other (like turning to the neighbor and start talking) were
      registered. The gathered data serve as empirical design basis for a virtual
      audience to be used in virtual training applications that stimulate the
      experiences of the participants in a realistic manner, thereby improving the
      experienced presence in the training application.

PMID- 22954860
TI  - Using portable EEG devices to evaluate emotional regulation strategies during
      Virtual Reality exposure.
AB  - As Virtual Reality (VR) is starting to be used to train emotional regulation
      strategies, it would be interesting to propose objective techniques to monitor
      the emotional reactions of participants during the virtual experience. In this
      work, the main goal is to analyze if portable EEG systems are adequate to monitor
      brain activity changes caused by the emotional regulation strategies applied by
      the participants. The EEG signals captured from subjects that navigate through a
      virtual environment designed to induce a negative mood will be compared between
      three experimental groups that will receive different instructions about the
      emotional regulation strategies to apply. The study will allow us to validate the
      possibilities of portable EEG devices to monitor emotional regulation strategies
      during VR exposure.

PMID- 22954861
TI  - Electro-physiological data fusion for stress detection.
AB  - In this work we describe the performance evaluation of a system for stress
      detection. The analysed data is acquired by following an experimental protocol
      designed to induce cognitive stress to the subjects. The experimental set-up
      included the recording of electroencephalography (EEG) and facial (corrugator and
      zygomatic) electromyography (EMG). In a preliminary analysis we are able to
      correlate EEG features (alpha asymmetry and alpha/beta ratio using only 3
      channels) with the stress level of the subjects statistically (by using averages
      over subjects) but also on a subject-to-subject basis by using computational
      intelligence techniques reaching classification rates up to 79% when classifying
      3 minutes takes. On a second step, we apply fusion techniques to the overall
      multi-modal feature set fusing the formerly mentioned EEG features with EMG
      energy. We show that the results improve significantly providing a more robust
      stress index every second. Given the achieved performance the system described in
      this work can be successfully applied for stress therapy when combined with
      virtual reality.

PMID- 22954862
TI  - Involving elderly users in design: techniques to collect preferences for
      Interactive Digital Television.
AB  - SeniorChannel is a European project that explores the potential of using an
      Interactive Digital Television (IDTV) to turn elderly people at home into an
      active audience. Techniques to involve elderly users in the requirement
      collection during the design phase should take into account the decrease in
      perception, cognition and motor abilities associated with aging. The paper
      describes the specific solutions adopted here to elicit users' contribution, as
      well as the contributed preferences in terms of IDTV content and interaction
      modalities.

PMID- 22954863
TI  - Auditory-visual integration of emotional signals in a virtual environment for
      cynophobia.
AB  - Cynophobia (dog phobia) has both visual and auditory relevant components. In
      order to investigate the efficacy of virtual reality (VR) exposure-based
      treatment for cynophobia, we studied the efficiency of auditory-visual
      environments in generating presence and emotion. We conducted an evaluation test
      with healthy participants sensitive to cynophobia in order to assess the capacity
      of auditory-visual virtual environments (VE) to generate fear reactions. Our
      application involves both high fidelity visual stimulation displayed in an
      immersive space and 3D sound. This specificity enables us to present and
      spatially manipulate fearful stimuli in the auditory modality, the visual
      modality and both. Our specific presentation of animated dog stimuli creates an
      environment that is highly arousing, suggesting that VR is a promising tool for
      cynophobia treatment and that manipulating auditory-visual integration might
      provide a way to modulate affect.

PMID- 22954864
TI  - User validation of an empathic virtual buddy against cyberbullying.
AB  - People are able to comfort others by talking about their problems. In our
      research, we are exploring whether computers can provide social support in a
      similar manner. Recently, we proposed a design for an empathic virtual buddy that
      supports victims of cyberbullying. To validate our approach in providing social
      support and to gather feedback from potential users, we performed an experiment
      (N = 30) to compare interaction with the buddy to reading a text. Both the buddy
      and the text received high scores; scores for the buddy were consistently higher.
      The difference was significant for the extent to which feelings were taken into
      account. These results indicate that participants liked to interact with the
      buddy and that they recognized the emotional cues emitted by the buddy, thus
      validating our approach in comforting users.

PMID- 22954865
TI  - Virtual representations of the self: engaging teenagers in emotional regulation
      strategies learning.
AB  - The aim of this paper is to present digital representations of humans (i.e.,
      avatars) that look like the self, applied to the Mental Health (MH) field.
      Virtual Representations of the Self (VRS) are in our opinion a tool with a great
      potential for engaging teenagers in emotional regulation strategies learning and
      an excellent example of new technology application to the basic concept in
      psychology field such as Bandura's modeling [1]. VRSs have already demonstrated
      their potential on human behavior modification (e.g. modification of physical
      activity; eating habits) in general population [2]. Thus, the same technology can
      bring in our opinion a lot to the Mental Health field, especially in emotional
      regulation learning. This paper presents a theoretical background and describes
      the methodology that we plan to apply in order to validate the efficacy of VRSs
      in clinical settings. Also, the implications of such technology and future
      research lines are discussed.

PMID- 22954866
TI  - Analysis of online social networking peer health educators.
AB  - This study seeks to determine whether peer leaders can be recruited to deliver a
      community-based health intervention using social media. African American and
      Latino men who have sex with men (MSM) were recruited as peer leaders for either
      an HIV prevention or general health intervention using social networking
      technologies. Peer leaders attended 3 training sessions on how to use social
      media for health behaviour change. Baseline and post-training questionnaires were
      given to ensure that peer leaders were qualified in using social media to
      communicate health information. Repeated measures ANOVA models and chi2 tests
      assessed differences in peer leader knowledge and comfort using social networking
      technologies pre- and post-training. Post-training, peer leaders were
      significantly more comfortable using social media to discuss sexual positions.
      Almost all peer leaders reported being comfortable using social media. There were
      no significant pre- and post-training differences on other knowledge or comfort
      measures. Results suggest that peer leaders can be recruited to conduct health
      interventions using social networking technologies. The discussed training plan
      can be adapted to health domains to ensure that peer leaders are qualified to
      conduct health interventions using social media.

PMID- 22954868
TI  - The use of VR distraction to decrease pain after laparoscopic bariatric surgery:
      a case study.
AB  - One of the advantages of laparoscopic bariatric surgery is the reduced level of
      postoperative pain. In some cases, however, the pain level may be high. This is a
      challenge for specialists. This case study explores the use of VR distraction in
      an 18 year-old patient who had undergone laparoscopic bariatric surgery and who
      reported pain during the postoperative period. The study was conducted in a Level
      III Private Hospital in Mexico City where the patient was hospitalized. The
      patient was administered standard analgesic during VR distraction, which lasted a
      total of 40 minutes divided into two sessions. The scores of three visual
      analogue scales and catastrophism were the dependent variables of this study. The
      scales were administered before and after the VR distraction intervention. The
      patient reported lower pain levels after VR distraction and reductions in some
      components of catastrophism. This study proves that VR distraction can be
      effective not only in reducing the physical component of pain (a notion that is
      already well established) but also the cognitive/affective component. More
      controlled studies of the issue are required.

PMID- 22954869
TI  - PHIT for duty, a mobile approach for psychological health intervention.
AB  - The goal of this effort is to support prevention of psychological health problems
      through innovation in mobile personal health assessment and self-help
      intervention (SHI). For the U.S. military, we are developing and evaluating a
      field-deployable personalized application, PHIT for DutyTM, to help build
      resilience in healthy troops and support prevention in high-risk personnel. PHIT
      for Duty is delivered using any smartphone or tablet with optional nonintrusive
      physiological and behavioral sensors for health status monitoring. The
      application integrates a suite of health assessments with an intelligent advisor
      that recommends, tailors, and presents self-help advisories. PHIT for Duty is
      intended for secondary prevention of psychological health problems in persons who
      have been exposed to psychological trauma and may be showing some symptoms of
      distress, but have not been diagnosed with any psychological disease or disorder.

PMID- 22954870
TI  - An online emotional regulation system to deliver homework assignments for
      treating adjustment disorders.
AB  - Adjustment Disorders (AD) is a very common mental health problem in primary care.
      Only general treatment guidelines are available for its treatment. Our research
      team has developed a cognitive-behavioural treatment (CBT) supported by Virtual
      reality (EMMA system) that has shown its utility in the treatment of AD. EMMA is
      a VR adaptive display that adapts its presentation to the patient' therapeutic
      needs. So far, researchers have been centered on how to use the Information and
      Communication Technologies to deliver treatment within the therapeutic context.
      TEO is a completely open Online Emotional Therapy web-based system that allows
      creating personalized therapeutic material. The patient can access this material
      over the Internet. Preliminary data about the acceptability of TEO system in a
      case study has already been obtained. The aim of the present work is to describe
      the session protocol regarding the homework assignments component in the
      treatment of AD designed in TEO system. Also, data about preferences and efficacy
      of TEO system versus traditional homework assignments implementation in a single
      case study with AD are presented. A web-based system of this kind increases the
      possibilities for therapy.

PMID- 22954871
TI  - Virtual reality in the treatment of body image disturbances after bariatric
      surgery: a clinical case.
AB  - Bariatric surgery is an operation on the stomach and/or intestines that helps
      patients with extreme obesity to lose weight. Even if bariatric surgery, compared
      with traditional obesity treatment, is more effective in reducing BMI, this
      approach does not achieve equal results in every patient. More, following
      bariatric surgery common problems are body image dissatisfaction and body
      disparagement: there is a significant difference between the weight loss
      clinicians consider successful (50% of excess weight) and the weight loss
      potential patients expect to achieve (at least 67% of the excess weight). The
      paper discusses the possible role of virtual reality (VR) in addressing this
      problem within an integrated treatment approach. More, the clinical case of a
      female bariatric patient who experienced body dissatisfaction even after a 30%
      body weight loss and a 62% excess body weight loss, is presented and discussed.

PMID- 22954872
TI  - Improving social behaviour in schizophrenia patients using an integrated virtual
      reality programme: a case study.
AB  - Social skills training programmes are among the treatments of choice in
      schizophrenia. Virtual reality (VR) can improve the results obtained with
      traditional social skills programmes by helping to generalize the acquired
      responses to patients' daily lives. We present the results of a case study
      involving the application of an integrated VR programme for social skills
      training. A 30-year-old woman with a well-established diagnosis of schizophrenia
      was enrolled in the study. She completed four baseline sessions, 16 treatment
      sessions and four follow-up sessions three months after the end of the treatment.
      Using a multiple baseline across-behaviours design, three target behaviours were
      analysed: facial emotion recognition, social anxiety and conversation time.
      Symptoms and social function variables were also assessed. The results showed a
      positive change in the three target behaviours and improvements in interpersonal
      communication, assertiveness and negative symptoms. The VR programme proved
      useful for training the patient's social behaviour and, consequently, for
      improving her performance.

PMID- 22954873
TI  - Real-time monitoring of behavioural parameters related to psychological stress.
AB  - We have developed a system, allowing real-time monitoring of human gestures,
      which can be used for the automatic recognition of behavioural correlates of
      psychological stress. The system is based on a low-cost camera (Microsoft
      Kinect), which provides video recordings capturing the subject's upper body
      activity. Motion History Images (MHIs) are calculated in real-time from these
      recordings. Appropriate algorithms are thereafter applied over the MHIs, enabling
      the real-time calculation of activity-related behavioural parameters. The
      system's efficiency in real-time calculation of behavioural parameters has been
      tested in a pilot trial, involving monitoring of behavioural parameters during
      the induction of mental stress. Results showed that our prototype is capable to
      effectively calculate simultaneously eight different behavioural parameters in
      real-time. Statistical analysis indicated significant correlations between five
      of these parameters and self-reported stress. The preliminary findings suggest
      that our approach could potentially prove useful within systems targeting
      automatic stress detection, through unobtrusive monitoring of subjects.

PMID- 22954874
TI  - Virtual reality for smoking cessation: a case report.
AB  - This study presents a case report describing the use of Virtual Stop Smoking
      (VSS) program. The VSS includes a multicomponent behavioural approach and a
      Virtual Reality graded exposure technique. The subject was a 22-year-old female
      who smoked 20 cigarettes per day. Six weekly 90-minute sessions were conducted
      once a week over a 6-week period. Measures of efficacy included the number of
      cigarettes smoked, breath carbon monoxide levels, and self-reported subjective
      craving. The results obtained supported the efficacy of VSS for smoking
      cessation.

PMID- 22954875
TI  - Therapeutic effectiveness of a virtual reality game in self-awareness after
      acquired brain injury.
AB  - Self-awareness deficits can manifest as a consequence of acquired brain injury
      decreasing the motivation and the adherence to the treatment. We present a
      multitouch system that promotes the role-playing and the self-assessment
      strategies and challenges the participants in a competitive context. This paper
      presents an initial clinical trial to study the effectiveness of the virtual
      system in the rehabilitation of the self-awareness skills.According the evolution
      of the participants in the Self-Awareness Deficits Interview and in the Spanish
      Social Skills Scale, the participants improve the perception of their deficits
      and disabilities.

PMID- 22954877
TI  - Use of a virtual integrated environment in prosthetic limb development and
      phantom limb pain.
AB  - Patients face two major difficulties following limb loss: phantom limb pain (PLP)
      in the residual limb and limited functionality in the prosthetic limb. Many
      studies have focused on decreasing PLP with mirror therapy, yet few have examined
      the same visual ameliorating effect with a virtual or prosthetic limb. Our study
      addresses the following key questions: (1) does PLP decrease through observation
      of a 3D limb in a virtual integration environment (VIE) and (2) can consistent
      surface electromyography (sEMG) signals from the VIE drive an advanced modular
      prosthetic limb (MPL)? Recorded signals from the residual limb were correlated to
      the desired motion of the phantom limb, and changes in PLP were scored during
      each VIE session. Preliminary results show an overall reduction in PLP and a
      trend toward improvement in signal-to-motion accuracy over time. These signals
      allowed MPL users to perform a wide range of hand motions.

PMID- 22954878
TI  - Earth of Wellbeing: a place to live positive emotions.
AB  - EARTH of Wellbeing is a technological application to induce and train positive
      emotions and enhance different psychological strengths. The system contains 3
      modules of activities: Park of Wellbeing, Wellbeing in the Nature and Book of
      Life. The objective of this paper is to describe the system and to offer data
      about its efficacy to induce positive affect in a sample of 30 participants who
      use EARTH three times a week along one month. This is a work in progress.

PMID- 22954879
TI  - FRIEND: a brain-monitoring agent for adaptive and assistive systems.
AB  - This paper presents an architectural design for adaptive-systems agents (FRIEND)
      that use brain state information to make more effective decisions on behalf of a
      user; measuring brain context versus situational demands. These systems could be
      useful for alerting users to cognitive workload levels or fatigue, and could
      attempt to compensate for higher cognitive activity by filtering noise
      information. In some cases such systems could also share control of devices, such
      as pulling over in an automated vehicle. These aim to assist people in everyday
      systems to perform tasks better and be more aware of internal states. Achieving a
      functioning system of this sort is a challenge, involving a unification of brain-
      computer-interfaces, human-computer-interaction, soft-computin deliberative multi
      agent systems disciplines. Until recently, these were not able to be combined
      into a usable platform due largely to technological limitations (e.g., size,
      cost, and processing speed), insufficient research on extracting behavioral
      states from EEG signals, and lack of low-cost wireless sensing headsets. We aim
      to surpass these limitations and develop control architectures for making sense
      of brain state in applications by realizing an agent architecture for adaptive
      (human-aware) technology. In this paper we present an early, high-level design
      towards implementing a multi-purpose brain-monitoring agent system to improve
      user quality of life through the assistive applications of psycho-physiological
      monitoring, noise-filtering, and shared system control.

PMID- 22954880
TI  - A motor imagery based brain-computer interface for stroke rehabilitation.
AB  - Brain-Computer Interfaces (BCIs) have been used to assist people with impairments
      since many years. In most of these applications the BCI is intended to substitute
      functions the user is no longer able to perform without help. For example BCIs
      could be used for communication and for control of devices like robotic arms,
      wheelchairs or also orthoses and prostheses. Another approach is not to replace
      the motor function itself by controlling a BCI, but to utilize a BCI for
      rehabilitation that enables the user to restore normal or "more normal" motor
      function. Motor imagery (MI) itself is a common strategy for motor rehabilitation
      in stroke patients. The idea of this paper is it to assist the MI by presenting
      online feedback about the imagination to the user. A BCI is presented that
      classifies MI of the left hand versus the right hand. Feedback is given to the
      user with two different strategies. One time by an abstract bar feedback, and the
      second time by a 3-D virtual reality environment: The left and right hand of an
      avatar in the 1st person's perspective in presented to him/her. If a motor
      imagery is detected, the according hand of the avatar moves. Preliminary tests
      were done on three healthy subjects. Offline analysis was then performed to (1)
      demonstrate the feasibility of the new, immersive, 3-D feedback strategy, (2) to
      compare it with the quite common bar feedback strategy and (3) to optimize the
      classification algorithm that detects the MI.

PMID- 22954881
TI  - A robotic & virtual reality orthopedic rehabilitation system for the forearm.
AB  - We describe a robotic and virtual reality system for the rehabilitation of the
      forearm. It consists of a robotic arm and VR scenarios with a dynamic model of
      the human upper limb. The system allows to assign specific tasks to perform
      within the virtual environments. The system simulates the actions of the patient
      limb and allows exhaustive exercising and motor control, giving visuomotor and
      haptic feedback and trajectory positioning guidance. The system aids to evaluate
      the mobility condition of the patient, to personalize the difficult level of the
      therapy and provides kinematic measures of the patient evolution. The patients
      recruitment phase has already started for clinical pilot studies.

PMID- 22954882
TI  - Psychosocial implications of avatar use in supporting therapy for depression.
AB  - Help4Mood is a novel intervention to support the treatment of depressive disorder
      using an embodied communicative agent (Avatar) to engage the user with therapy
      tasks. We conducted 10 focus groups with patients and mental health
      professionals, in the UK, Spain and Romania, in order to explore issues around
      usability and contextual fit. Emergent themes related to the design and use of
      Avatars indicated the value of configurability for optimising personalisation and
      perceived trustworthiness; the importance of supplementing rather than replacing
      face-to-face interaction, and perceptions of the agent as therapeutic ally or
      supportive friend. The use of Avatars in psychotherapy is relatively new and its
      acceptability, value and risks are unknown. These results indicate that users
      wish to engage with Avatars that meet their personal preferences and fit
      appropriate role expectations. The perception of Avatar as colleague or friend
      raises conceptual and ethical issues which merit further research.

PMID- 22954883
TI  - GameTeen: new tools for evaluating and training emotional regulation strategies.
AB  - The aim of this paper is to describe GameTeen, a novel instrument for the
      assessment and training of Emotional Regulation (ER) strategies in adolescent
      population. These new tools are based on the use of 3D serious games that can be
      played under different settings. The evolution of ER strategies will be monitored
      in two ways depending on the setting where the tool is presented. Firstly, in the
      laboratory, physiological signals and facial expressions of participants will be
      recorded. Secondly, in real life settings, ecological momentary assessment tools
      will be used to obtain answers from the subjects using their mobile phone. The
      goal is to obtain more attractive and reliable tools to evaluate and train ER
      strategies.

PMID- 22954884
TI  - Innovative ICT solutions to improve treatment outcomes for depression: the
      ICT4Depression project.
AB  - Depression is expected to be the disorder with the highest disease burden in high
      income countries by the year 2030. ICT4Depression (ICT4D) is a European FP7
      project, which aims to contribute to the alleviation of this burden by making use
      of depression treatment and ICT innovations. In this project we developed an ICT
      based system for use in primary care that aims to improve access as well as
      actual care delivery for depressed adults. Innovative technologies within the
      ICT4D system include 1) flexible self-help treatments for depression, 2)
      automatic assessment of the patient using mobile phone and web-based
      communication 3) wearable biomedical sensor devices for monitoring activities and
      electrophysiological indicators, 4) computational methods for reasoning about the
      state of a patient and the risk of relapse (reasoning engine) and 5) a flexible
      system architecture for monitoring and supporting people using continuous
      observations and feedback via mobile phone and the web. The general objective of
      the ICT4D project is to test the feasibility and acceptability of the ICT4D
      system within a pilot study in the Netherlands and in Sweden during 2012 and
      2013.

PMID- 22954888
TI  - Towards a high-resolution flow camera using artificial hair sensor arrays for
      flow pattern observations.
AB  - Flow-sensor arrays uncover the potential to measure spatio-temporal flow patterns
      rather than flow measurements at just a single point. We present in this paper
      the developments in design, fabrication and interfacing of biomimetic flow-sensor
      arrays, inspired by flow-sensitive organs (cerci) of crickets. For the purpose of
      high-resolution flow field visualization by our artificial hair flow-sensor
      arrays, various array-interfacing schemes are discussed and compared. Frequency
      division multiplexing (FDM) is shown to be an attractive method for efficient
      interrogation of capacitive array sensors. Using silicon-on-insulator technology
      with deep trench isolation structures, hair-based flow-sensors with differential
      capacitive read-out, arranged in single-chip arrays, have been successfully
      fabricated. FDM is implemented and used to interrogate individual hair sensors
      providing simultaneous real-time flow measurements from multiple hairs. This
      powerful approach is demonstrated by reconstruction of the field of a harmonic
      dipole field at the position of the hairs and by localizing this dipole source
      relative to the array elements.

PMID- 22954889
TI  - Enhanced indirubin production in recombinant Escherichia coli harboring a flavin
      containing monooxygenase gene by cysteine supplementation.
AB  - In our previous study, a batch fermentation of recombinant Escherichia coli
      DH5alpha cells harboring the fmo gene from Methylophaga aminisulfidivorans MP(T)
      produced indirubin (5.0mg/L) and indigo (920mg/L) in a 5L fermenter containing
      tryptophan medium (2g/L tryptophan, 5g/L yeast extract, 10g/L NaCl). In this
      study, it was found that indirubin production greatly increased when 0.36g/L
      cysteine was added to the tryptophan medium, although cysteine inhibited the
      growth of the recombinant E. coli harboring the fmo gene. However, the addition
      of cysteine did not inhibit the expression level and activity of FMO in the cell.
      Indigo was synthesized by the dimerization of two 3-hydroxyindole molecules under
      the non-enzymatic reaction. Cysteine influenced the regioselectivity of FMO and
      enhanced the synthesis of 2-hydroxyindole instead of 3-hydroxyindole, which might
      function to increase indirubin production. The optimal culture conditions for
      indirubin production in tryptophan medium were determined from the response
      surface methodology analysis: 2g/L tryptophan, 5g/L yeast extract, 10g/L NaCl,
      0.36g/L (3mM) cysteine, pH 8.0 at 35 degrees C. Under these conditions, the
      recombinant E. coli cells were capable of producing 223.6mg/L of indirubin from
      2g/L of tryptophan. The intracellular accumulation of the indirubin crystals
      might stress the cell, which may be a main reason for the poor growth of the
      recombinant E. coli pBlue 1.7.

PMID- 22954891
TI  - Physiological tolerance and stoichiometric potential of cyanobacteria for
      hydrocarbon fuel production.
AB  - Cyanobacteria are capable of directly converting sunlight, carbon dioxide and
      water into hydrocarbon fuel or precursors thereof. Many biological and non
      biological factors will influence the ability of such a production system to
      become economically sustainable. We evaluated two factors in engineerable
      cyanobacteria which could potentially limit economic sustainability: (i)
      tolerance of the host to the intended end-product, and (ii) stoichiometric
      potential for production. Alcohols, when externally added, inhibited growth the
      most, followed by aldehydes and acids, whilst alkanes were the least inhibitory.
      The growth inhibition became progressively greater with increasing chain-length
      for alcohols, whilst the intermediate C6 alkane caused more inhibition than both
      C3 and C11 alkane. Synechocystis sp. PCC 6803 was more tolerant to some of the
      tested chemicals than Synechococcus elongatus PCC 7942, particularly ethanol and
      undecane. Stoichiometric evaluation of the potential yields suggested that there
      is no difference in the potential productivity of harvestable energy between any
      of the studied fuels, with the exception of ethylene, for which maximal
      stoichiometric yield is considerably lower. In summary, it was concluded that
      alkanes would constitute the best choice metabolic end-product for fuel
      production using cyanobacteria if high-yielding strains can be developed.

PMID- 22954890
TI  - Replacement of the human cytomegalovirus promoter with fish enhancer and core
      elements to control the expression of the G gene of viral haemorrhagic septicemia
      virus (VHSV).
AB  - This work explores some of the possibilities to replace human cytomegalovirus
      (CMV) core and/or enhancer promoter control elements to create new expression
      vectors for use with fish. The work is relevant to fish vaccination, since DNA
      vaccines use eukaryotic expression plasmids controlled by the human
      cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as
      viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish
      viral European diseases. To reduce possible homologous recombination with fish
      genome, core and enhancer sequences from fish origin, such as trout interferon
      inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR)
      and carp beta-actin (AE6), were combined with those of CMV to design alternative
      hybrid promoters. The substitution of CMV core and/or enhancer with the
      corresponding elements of Mx or the LTR core maintained a similar in vitro
      protein G expression level than that obtained by using the CMV promoter. Vectors
      using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores
      showed the highest in vitro protein G expression levels. Furthermore, synthetic
      constructs using the Mx enhancer maintained their polyI:C induction capabilities
      despite the core used. Some of these hybrid promoters might contribute to the
      development of all-fish-vectors for DNA vaccines while others might be useful for
      more basic studies.

PMID- 22954892
TI  - Optimization of SCF feeding regimen for ex vivo expansion of cord blood
      hematopoietic stem cells.
AB  - Stem cell factor (SCF) plays important roles in ex vivo expansion of
      hematopoietic stem cells (HSCs). In this study, the effects of dose and feeding
      time of SCF on ex vivo expansion of CD34(+) cells were investigated in serum-free
      medium supplemented with a cytokine cocktail composed of SCF, thrombopoietin
      (TPO) and flt3-ligand (FL). Among the four tested doses (0, 5, 50 and 500ng/mL),
      a SCF dose of 50ng/mL was demonstrated to be most favorable for ex vivo expansion
      of CD34(+) cells, which resulted in 34.22+/-10.80 and 8.89+/-1.25 folds of
      expansion regarding total cells and CD34(+) cells, respectively. Meanwhile, the
      specific growth rate of cells, the consumption rate of SCF and the percentage of
      CD34(+)c-kit(+) cells during the 21-day culture process were analyzed. The
      results indicated that initial 4-day period was a critical stage for SCF
      functioning on CD34(+) cells during ex vivo expansion. Based on this, a modified
      SCF feeding regimen was proposed, in which SCF (50ng/mL) was only supplemented on
      day 0 in the cytokine cocktail and cells were then fed with TPO and FL till the
      end of culture. It was found that this SCF feeding regimen could expand CD34(+)
      cells efficiently, thus providing a cost-effect expansion protocol for HSCs.

PMID- 22954893
TI  - Evaluation of the effect of duloxetine treatment on functioning as measured by
      the Sheehan disability scale:  pooled analysis of data from six randomized,
      double-blind, placebo-controlled clinical studies.
AB  - The purpose of this work is to describe the effect of duloxetine on functioning
      as measured by the Sheehan disability scale (SDS) compared with placebo in
      patients with major depressive disorder (MDD). Pooled data from six randomized,
      parallel, double-blind, placebo-controlled duloxetine studies in adult MDD
      patients were analyzed at the short-term (7-13 weeks) and the long-term (>24
      weeks) endpoint. The primary variable was the SDS total score. Secondary
      variables included functional remission (SDS total <= 6) rates, Hamilton rating
      scale for depression total score, and pain visual analog scale. Analysis of
      covariance and logistic regression methods were used to assess differences in
      treatment and identify prognostic baseline factors. In total, 2496 patients (1424
      duloxetine; 1072 placebo) were included. The between-treatment difference of 
      2.52 between duloxetine and placebo in the SDS total score at the short-term
      endpoint was statistically significant in favor of duloxetine vs. placebo (95%
      confidence interval: -3.17, -1.87; P < 0.001). The endpoint functional remission
      rates were 39.5% with duloxetine and 28.7% with placebo. Time since first
      depression episode, antidepressant pretreatment (yes/no), baseline visual analog
      scale pain (<=30 / >30 mm), and sex were significant prognostic factors. The
      effect of duloxetine was maintained at the long-term endpoint. Duloxetine is
      effective in improving MDD patients' functioning. Further antidepressant studies
      focusing on functioning would be helpful.

PMID- 22954894
TI  - Drosophila neuroligin 1 regulates synaptic growth and function in response to
      activity and phosphoinositide-3-kinase.
AB  - Neuroligins are postsynaptic neural cell adhesion molecules that mediate synaptic
      maturation and function in vertebrates and invertebrates, but their mechanisms of
      action and regulation are not well understood. At the Drosophila larval
      neuromuscular junction (NMJ), previous analysis demonstrated a requirement for
      Drosophila neuroligin 1 (dnlg1) in synaptic growth and maturation. The goal of
      the present study was to better understand the effects and mechanisms of loss-of
      function and overexpression of dnlg1 on synapse size and function, and to
      identify signaling pathways that control dnlg1 expression. Consistent with
      reduced synapse size, evoked excitatory junctional currents (EJCs) were
      diminished in dnlg1 mutants but displayed normal Ca(2+) sensitivity and short
      term plasticity. However, postsynaptic function was also perturbed, in that
      glutamate receptor staining and the distribution of amplitudes of miniature
      excitatory junctional currents (mEJCs) were abnormal in mutants. All the above
      phenotypes were rescued by a genomic transgene. Overexpression of dnlg1 in muscle
      resulted in synaptic overgrowth, but reduced the amplitudes of EJCs and mEJCs.
      Overgrowth and reduced EJC amplitude required Drosophila neurexin 1 (dnrx1)
      function, suggesting that increased DNlg1/DNrx1 signaling attenuates synaptic
      transmission and regulates growth through a retrograde mechanism. In contrast,
      reduced mEJC amplitude was independent of dnrx1. Synaptic overgrowth, triggered
      by neuronal hyperactivity, absence of the E3 ubiquitin ligase highwire, and
      increased phosphoinositide-3-kinase (PI3K) signaling in motor neurons reduced
      synaptic DNlg1 levels. Likewise, postsynaptic attenuation of PI3K, which
      increases synaptic strength, was associated with reduced DNlg1 levels. These
      observations suggest that activity and PI3K signaling pathways modulate growth
      and synaptic transmission through dnlg1-dependent mechanisms.

PMID- 22954896
TI  - Entering a world of uncertainty: community nurses' engagement with information
      and communication technology.
AB  - Achieving adoption, use, and integration of information and communication
      technology by healthcare clinicians in the workplace is recognized as a challenge
      that requires a multifaceted approach. This article explores community health
      nurses' engagement with information and communication technology as part of a
      larger research project that investigated the delivery of self-management support
      to people with chronic obstructive pulmonary disease. Following a survey of
      computer skills, participants were provided with computer training to support use
      of the project information system. Changes in practice were explored using action
      research meetings and individual semistructured interviews. Results highlight
      three domains that affected nurses' acceptance, utilization, and integration of
      information and communication technology into practice; environmental issues;
      factors in building capacity, confidence, and trust in the technology; and
      developing competence. Nurses face individual and practice challenges when
      attempting to integrate new processes into work activities, and the use of
      participatory models to support adoption is recommended.

PMID- 22954895
TI  - Mouse models of Parkinson's disease associated with mitochondrial dysfunction.
AB  - Despite years of intensive research, the understanding of Parkinson's disease
      (PD) is still rudimentary. Genetic causes of rare familial cases have offered
      venues of investigation, and interestingly, have strengthened the case for a
      mitochondrial dysfunction in the pathogenesis of PD. Mouse models, where these
      and other mitochondrial-related genes are affected are helping not only in
      understanding PD, but also in providing a powerful tool to test therapeutics. In
      this review, we will discuss the different characteristics of these mouse models.
      This article is part of a Special Issue entitled 'Mitochondrial function and
      dysfunction in neurodegeneration'.

PMID- 22954897
TI  - Sun protection counseling by pediatricians has little effect on parent and child
      sun protection behavior.
AB  - OBJECTIVE: To compare counseling concerning sun protection and outdoor exercise
      with the parent's report of the behavior of a child aged 9-16 years old. STUDY
      DESIGN: Structured interviews of medical personnel in 3 Chicago area practices
      elicited information about counseling methods and recommendations. In each
      practice, a convenience sample of parents completed a self-reported survey of
      their and their child's behavior. RESULTS: Sun protection counseling occurred
      more frequently than exercise counseling in all practices (P = .014). Sun
      protection counseling was associated with parental prompting (P = .004),
      performing a summer camp physical (P = .002), and the child having a sunburn (P =
      .003). After controlling for the child's age, sex, and skin tone, sun protection
      counseling was not associated with the child's use of sun protection. In
      multivariate analysis of the child's sun protection behavior, parental sunburns,
      indoor tanning in the last 12 months, perception of skin cancer risk, and sun
      protection self-efficacy were significant (P = .02). Children who pursued outdoor
      sports were twice as likely to use inadequate sun protection and sustain sunburns
      (CI 1.3-1.7). CONCLUSIONS: The child's sun protection behavior was influenced by
      parental sun protection, parental perception of skin cancer risk, and parental
      sun protection self-efficacy; therefore, sun protection for children needs to be
      aimed at parents as well as children. Communication with parents in a way that
      incorporates the principles of motivational interviewing may be more effective in
      promoting behavioral change than admonitions to use sunscreen.

PMID- 22954898
TI  - Phosphoramidate derivatives of acyclovir: synthesis and antiviral activity in HIV
      1 and HSV-1 models in vitro.
AB  - The antiviral activity against HIV and HSV and the chemical stability of ACV
      phosphoramidate derivatives were studied. The phosphoramidates of ACV
      demonstrated moderate activity. The best compound appeared to be 9-(2
      hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus
      replication in pseudo-HIV-1 particles by 50% at 50 MUM. It also inhibited
      replication of wild-type HSV-1 (9.7 MUM) as well as an acyclovir-resistant strain
      (25 MUM). None of the synthesised compounds showed any cytotoxicity.

PMID- 22954899
TI  - Novel interleukin-5 inhibitors based on hydroxyethylaminomethyl-4H-chromen-4-one
      scaffold.
AB  - Hydroxyethylaminomethyl-4H-chromenones were previously discovered as fairly
      strong IL-5 inhibitor. For determination of detail structure activity
      relationship, N-substituted hydroxyethylaminomethylchromenones 4a-n were prepared
      and evaluated for their IL-5 inhibitory activity. Shifting the hydrophobic group
      to nitrogen from 1-position of hydroxyethylamino moiety of
      hydroxyethylaminomethyl-4H-chromenones enhances the activity. The increment in
      bulkiness or hydrophobicity of alkyl side chain at amino group increases the
      activity. The same level of activity of 5-(cyclohexylmethoxy)-3-(N-benzyl-2
      hydroxyethylaminomethyl)-4H-chromenone analogs regardless of hydrophobic or
      hydrophilic substituents at 4th position of phenyl ring might infer the existence
      of tunnel structure in the putative receptor for accepting these side chains.

PMID- 22954900
TI  - Widespread changes of white matter microstructure in obsessive-compulsive
      disorder: effect of drug status.
AB  - Diffusion tensor imaging (DTI) allows the study of white matter (WM) structure.
      Literature suggests that WM structure could be altered in obsessive-compulsive
      disorder (OCD) proportional to the severity of the disease. Heterogeneity of
      brain imaging methods, of the studied samples, and of drug treatments make
      localization, nature, and severity of the WM abnormalities unclear. We applied
      Tract-Based Spatial Statistics (TBSS) of DTI measures to compare fractional
      anisotropy (FA), mean, axial, and radial diffusivity of the WM skeleton in a
      group of 40 consecutively admitted inpatients affected by severe OCD (18 drug
      naive, and 22 with an ongoing drug treatment) and 41 unrelated healthy volunteers
      from the general population. Data were analyzed accounting for the effects of
      multiple comparisons, and of age, sex, and education as nuisance covariates.
      Compared to controls, OCD patients showed a widespread reduction of FA with a
      concurrent increase of mean and radial diffusivity. In no brain areas patients
      had higher FA or lower diffusivity values than controls. These differences were
      observed in drug-treated patients compared to drug-naive patients and healthy
      controls, which in turn did not differ among themselves in any DTI measure.
      Reduced FA with increased mean and radial diffusivity suggests significant
      changes in myelination of WM tracts, without axonal loss. Drug treatments could
      modify the structure of cell membranes and myelin sheaths by influencing cellular
      lipogenesis, cholesterol homeostasis, autophagy, oligodendrocyte differentiation
      and remyelination. Changes of DTI measures in drug-treated OCD patients could
      reflect pathophysiological underpinnings of OCD, or a yet unexplored part of the
      mechanism of action of drugs.

PMID- 22954901
TI  - [Controversies in the management of breast cancer in women of advanced age].

PMID- 22954902
TI  - 24-hour profiles of circulating ghrelin and peptide YY are inversely associated
      in normal weight premenopausal women.
AB  - Peptide YY (PYY) and ghrelin (GHR) may modulate one another's actions within the
      hypothalamus. Peripheral infusion of PYY in humans acutely suppresses circulating
      concentrations of GHR. Whether an association between PYY and GHR exists in the
      peripheral circulation of humans over 24h is unknown. The purpose of this study
      was to determine if circulating concentrations of PYY and GHR were significantly
      associated over 24h in humans. Participants (n=13) were normal weight, moderately
      active, women ages 18-24 yr. Blood samples were obtained q10 min for 24 h and
      assayed using RIA for total PYY and total GHR hourly from 0800 to 1000 h and 2000
      to 0800 h and q20 min from 1000 to 2000 h. Dietary intake during the 24 h
      procedure was comprised of 55% carbohydrates, 30% fat, and 15% protein (three
      meals and a snack). Statistical analyses included linear mixed-effects modeling
      to test whether PYY predicted GHR concentrations over 24h. Participants weighed
      57.0+/-1.5 kg and had 26.1+/-1.5% body fat (15.0+/-1.1 kg), 42.1+/-1.1 kg fat
      free mass, a BMI of 21.3+/-0.5 kg/m(2) and RMR of 1072+/-28 kcal/24 h. Visually,
      PYY and GHR exhibited an inverse association over nearly the entire 24h period.
      Statistically, circulating concentrations of 24 h PYY predicted 24 h GHR
      (ghrelin=1860.51-2.14*PYY; p=0.04). Circulating concentrations of PYY are
      inversely associated with GHR over 24 h. These data provide evidence that PYY may
      contribute to the modulation of the secretion of GHR in normal weight,
      premenopausal women over a 24 h period and supports similar inferences from
      experimental studies in animals and humans.

PMID- 22954903
TI  - Sex differences in white matter development during adolescence: a DTI study.
AB  - Adolescence is a complex transitional period in human development, composing
      physical maturation, cognitive and social behavioral changes. The objective of
      this study is to investigate sex differences in white matter development and the
      associations between intelligence and white matter microstructure in the
      adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial
      statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to
      17 years, longitudinal DTI data were recorded from each subject at two time
      points that were one year apart. We used TBSS to analyze the diffusion indices
      including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity
      (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years)
      continued to demonstrate white matter maturation, whereas girls appeared to reach
      mature levels earlier. In addition, we identified significant positive
      correlations between FA and full-scale intelligence quotient (IQ) in the right
      inferior fronto-occipital fasciculus when both sexes were looked at together.
      Only girls showed significant positive correlations between FA and verbal IQ in
      the left cortico-spinal tract and superior longitudinal fasciculus. The
      preliminary evidence presented in this study supports that boys and girls have
      different developmental trajectories in white matter microstructure.

PMID- 22954904
TI  - Phenylephrine-induced hypertension during transient middle cerebral artery
      occlusion alleviates ischemic brain injury in spontaneously hypertensive rats.
AB  - Arterial hypertension is a major risk factor for ischemic stroke. However, the
      management of preexisting hypertension is still controversial in the treatment of
      acute stroke in hypertensive patients. The present study evaluates the influence
      of preserving hypertension during focal cerebral ischemia on stroke outcome in a
      rat model of chronic hypertension, the spontaneously hypertensive rats (SHR).
      Focal cerebral ischemia was induced by transient (1h) occlusion of the middle
      cerebral artery, during which mean arterial blood pressure was maintained at
      normotension (110-120mm Hg, group 1, n=6) or hypertension (160-170mm Hg, group 2,
      n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were
      performed serially at five different time points: before and during ischemia, and
      at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated
      from apparent diffusion coefficient maps and T2-weighted images. Regional
      cerebral blood flow (rCBF) was measured within and outside the perfusion
      deficient lesion and in the corresponding regions of the contralesional
      hemisphere. Neurological deficits were evaluated after reperfusion. Infarct
      volume, edema, and neurological deficits were significantly reduced in group 2
      vs. group 1. In addition, higher values and rapid restoration of rCBF were
      observed in group 2, while rCBF in both hemispheres was significantly decreased
      in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury
      in SHR by increasing collateral circulation to the ischemic region and allowing
      rapid restoration of rCBF. The data suggest that maintaining preexisting
      hypertension is a valuable approach to managing hypertensive patients suffering
      from acute ischemic stroke.

PMID- 22954905
TI  - One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone
      and ziprasidone effectiveness in antipsychotic-naive patients with a first
      episode psychosis.
AB  - The aim of this study was to compare the 12-month effectiveness of several second
      generation antipsychotic drugs, with that of haloperidol in never-treated
      patients with first-episode psychosis. In total, 114 patients without life time
      exposure to any psychotropic medication were randomized to haloperidol,
      olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to
      all-cause discontinuation. Secondary outcomes included discontinuation rates and
      symptom change as measured by the Positive and Negative Syndrome Scale (PANSS).
      The overall discontinuation rate 64%. At 12 months, the proportion of patients
      discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for
      risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to
      antipsychotic discontinuation was higher in patients randomized to second
      generation antipsychotics than in those taking haloperidol. Significantly lower
      discontinuation was noted in patients on olanzapine than on haloperidol, or
      ziprasidone. Our results suggest that olanzapine might lead to longer treatment
      continuation in treatment naive FEP patients than haloperidol and, possibly
      ziprasidone. Global psychopathology was significantly less reduced by haloperidol
      than with each individual SGA in this earliest phase of treatment.

PMID- 22954906
TI  - Sparse decoding of multiple spike trains for brain-machine interfaces.
AB  - Brain-machine interfaces (BMIs) rely on decoding neuronal activity from a large
      number of electrodes. The implantation procedures, however, do not guarantee that
      all recorded units encode task-relevant information: selection of task-relevant
      neurons is critical to performance but is typically performed based on
      heuristics. Here, we describe an algorithm for decoding/classification of
      volitional actions from multiple spike trains, which automatically selects the
      relevant neurons. The method is based on sparse decomposition of the high
      dimensional neuronal feature space, projecting it onto a low-dimensional space of
      codes serving as unique class labels. The new method is tested against a range of
      existing methods using simulations and recordings of the activity of 1592 neurons
      in 23 neurosurgical patients who performed motor or speech tasks. The parameter
      estimation algorithm is orders of magnitude faster than existing methods and
      achieves significantly higher accuracies for both simulations and human data,
      rendering sparse decoding highly attractive for BMIs.

PMID- 22954907
TI  - [Role of miR-155 in myasthenia gravis and effect of dexamethasone on miR-155].
AB  - OBJECTIVE: To determine the role of miR-155 in the pathogenesis of generalized
      myasthenia gravis (GMG) and the effect of dexamethasone (DXM) on miR-155.
      METHODS: The expression of miR-155 in B cells from the GMG patients and healthy
      controls was analyzed by qPCR. The B cells were cultured with DXM and PBS. The B
      cell proliferation was examined by MTT; CD80 and CD86 frequencies were detected
      by flow cytometry; and anti-AChRIgG and isotypes anti-AChR-IgG1, 2, 3 in the
      supernatant were detected by ELISA. RESULTS: qPCR revealed that the expression of
      miR-155 in the B cells was much higher than that in the controls, and the miR155
      expression decreased after DXM treatment. flow cytometry showed that there was no
      significant difference in the proliferation and the expressions of CD80 and CD86
      in the B cells between the DXM group and the PBS group. The concentration of anti
      AChR-IgG1 was obviously lower in the DXM group than in the PBS group, but the
      concentration of anti-AChRIgG, anti-AChR-IgG2, and anti-AchR-IgG3 was similar.
      CONCLUSION: high expression of miR-155 may be associated with myasthenia gravis
      progression. DXM may disturb the antibody class switch of B cells by suppressing
      the expression of miR-155 and improve the symptom of MG patients.

PMID- 22954908
TI  - Total saponins of Cornus officinalis Sieb. ameliorates the endothelium dependent
      relaxation of mesenteric artery by regulating nitric oxide release in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: To explore the effects of total saponins of Cornus officinalis Sieb.
      (TSCO) on the contractility and relaxation of mesenteric artery in streptozotocin
      (STZ)-induced diabetic rats. METHODS: Sprague Dawley rats were administrated STZ
      intra-peritoneally at a dosage of 60 mg/kg to induce diabetes. TSCO was
      administrated at a dosage of 60 mg/kg or 120 mg/kg (per os) to the diabetic rats
      for 28 days. Glucose and insulin in the serum as well as the responsiveness of
      mesenteric artery rings were determined. RESULTS: TSCO decreased the contractile
      responsiveness to phenylephrine of mesenteric artery rings from diabetic rats,
      but increased the reactivity to acethylcholine. TSCO (120 mg/kg) ameliorated the
      baseline release of nitric oxide of mesenteric artery, but had little effect on
      the induced release of nitric oxide. Rosiglitazone had less effect on the
      mesenteric artery function than that of TSCO, though it was more effective on
      lowering blood glucose. CONCLUSION: The effects of TSCO on mesenteric artery of
      diabetic rats are dose dependent, and are possibly exerted by lowering blood
      glucose and ameliorating the release of nitric oxide in the endothelium.

PMID- 22954909
TI  - [Screening of membrane antigen differentially expressed in androgen-dependent
      prostate cancer and androgen-independent prostate cancer].
AB  - OBJECTIVE: To determine the screening of the expression of membrane proteins in
      androgen-dependent prostate cancer (ADPC) and androgen-independent prostate
      cancer (AIPC) and to explore the mechanism of membrane proteins in these two
      cancers. METHODS: Serum samples were collected from 3 patients with ADPC and
      another 3 patients with AIPC. The serum was incubated with ADPC cell line LNCaP
      and/or AIPC cell line PC-3 and detected by immunoprecipitation and Western blot.
      Differentially expressed proteins between ADPC and AIPC identified by mass
      spectrometry were compared and their expression level and location were analyzed
      by immunofluorescence. RESULTS: Altogether 11 membrane proteins were identifited,
      such as the Neural-Cadherin precursor, ER60 precursor, Claudin-4, and so on.
      Immunofluorescence revealed that the expression level of Claudin-4 in PC-3 cells
      was higher than in LNCaP cells. CONCLUSION: We can use the screening method to
      study membrane proteins in prostate cancer. Claudin-4 may play an important role
      in the pathogenesis and the development of AIPC.

PMID- 22954910
TI  - Clinical analysis of 12 patients caused by long-acting anticoagulant rodenticide
      occult poisoning.
AB  - OBJECTIVE: To explore the clinical characteristics and diagnosis and treatment of
      occult poisoning caused by long-acting anticoagulant rodenticides. METHOD:
      Records of 12 patients from July 2008 to April 2011 diagnosed as anticoagulant
      rodenticide occult poisoning, who had been misdiagnosed initially at other
      hospitals were analyzed retrospectively. Elements from the records included
      clinical symptoms and signs, laboratory findings for prothrombin time (PT) and
      activated partial prothrombin time (APTT), and initial misdiagnosis and treatment
      outcome at our hospital. RESULTS: The clinical presentations of patients were
      insidious and serious, often presented as skin ecchymose, hematuria, menorrhagia
      and gastrointestine bleeding. Laboratory examinations showed prolonged PT and
      APTT; bleeding was controlled effectively by administoring vitamin K1 daily.
      There were statistical difference between PT and APTT before and after the
      treatment (P<0.01). CONCLUSION: Coagulation disorders might be caused by the
      reduced acquisition in vitamin K dependent coagulation factors, which tends to be
      neglected due to a hidden medical history, delayed signs of poisoning, and
      various organs involved. A detailed patient history and systematic review may
      improve the diagnostic accuracy. Once diagnosed is made, vitamin K1 should be
      given as soon as possible.

PMID- 22954911
TI  - [Effect of DNA hypermethylation on NOR1 promoter activity and expression].
AB  - OBJECTIVE: To analyze the effect of DNA hypermethylation on NOR1 promoter
      activity and expression. METHODS: NOR1 promoter plasmids were treated with SssI
      methyltransferase. The plasmids were modified by sodium bisulfite and purified.
      Sodium bisulfite-modified plasmids were subjected to PCR with primers designed to
      analyze the methylation status of 26 CpG sites in a 311-bp region of the NOR1
      promoter. Cells were transfected by methylated or mock-methylated promoter
      plasmids. The promoter activities were assessed by the luciferase levels of cell
      lysates or by directly observing GFP expression under fluorescence microscope.
      HL60 cells were treated with different concentrations of 5-aza-dC. Total RNA was
      isolated from harvested cells. Real-time RT-PCR was used to measure the
      expression level of NOR1 mRNA. RESULTS: Bisulfite sequencing confirmed that SssI
      methyltransferase treatment successfully resulted in intensive hypermethylation
      of the NOR1 promoter plasmids. The promoter activity of NOR1 promoter plasmids
      was totally blocked by SssI methyltransferase treatment. NOR1 expression levels
      in HL60 cells were restored by 5-aza-dC treatment. CONCLUSION: NOR1 promoter
      plasmids are intensively hypermethylated by SssI methyltransferase treatment. The
      promoter activity of NOR1 promoter plasmids are totally blocked by SssI
      methyltransferase treatment. The 5-aza-dC treatment may restore the endogenous
      NOR1 mRNA level in HL60 cells.

PMID- 22954912
TI  - [Effect of intrathecal sufentanil and protein kinase C inhibitor on pain
      threshold and the expression of NMDA receptor/ CGRP in spinal dorsal horn in rats
      with neuropathic pain].
AB  - OBJECTIVE: To investigate the effect of intrathecal sufentanil and protein kinase
      C inhibitor on pain threshold and the expression of N-methyl-D-aspartate
      receaptors (NMDAR)/calcitonin generelated peptide (CGRP) in spinal dorsal horn in
      rats with neuropathic pain. METHODS: Fifty-four healthy male Sprague-Dawley rats
      were randomly divided into 6 groups (9 in each group). The rats in the sham
      group(Group S) + spared nerve injury (SNI), SP+SNI, and P+SNI were intrathecally
      injected sufentanil (1 MUg), sufentanil (1 MUg) and chelerythrine chloride (11
      MUg), chelerythrine chloride (11 MUg) followed by 10 MUL normal saline once every
      day for 14 days postoperatively, respectively. Similarly, rats in the control
      group (Group C), the sham group (Group S), and SNI model group (Group SNI) were
      intrathecally injected 20 MUL normal saline in the uniform interval. Pain
      behaviours were measured on Day 1 pre-surgery and on Day 1, 2, 7, and 14 after
      the intrathecal injection. The expressions of NMDAR and CGRP in the spinal dorsal
      horn of L5 segment were determined by immunohistochemistry on Day 2, 7, and 14
      after the intrathecal injection. RESULTS: Compared with Group C and Group S,
      mechanical allodynia threshold in group SNI was decreased after the surgery
      (P<0.01), and expressions of NMDAR and CGRP immunoreactive soma in the spinal
      dorsal horn was significantly increased (P<0.01). Mechanical stimulation pain
      threshold was elevated in Group S+SNI, Group P+SNI, and Group SP+SNI compared
      with Group SNI (P<0.01), while expressions of NMDAR and CGRP immunoreactive soma
      in Group S+SNI, Group P +SNI, and Group SP+SNI were significantly decreased
      (P<0.05 or 0.01). CONCLUSION: Intrathecal administration of sulfentanil and
      protein kinase C inhibitor can provide significant antinociception in rats with
      neuropathic pain and obviously inhibit the upregulation of NMDAR and CGRP
      expressions in the spinal dorsal horn of SNI rat models.

PMID- 22954913
TI  - [Concentration increase in Hcy and anti-CCP antibody in the serum of depression
      rat model induced by chronic unpredictable mild stress].
AB  - OBJECTIVE: To observe the change of serum homocysteine (Hcy) and anti
      citrullinated peptide (CCP) antibody concentration in depression rat model
      induced by chronic unpredictable mild stress (CUMS), and to explore the
      immunologic mechanism of depression and the relation between depression and its
      autoimmunity. METHODS: Sixty adult male SD rats were randomly divided into 2
      groups, 30 rats in each group, which were divided into 3 subgroups: a normal
      control group, a model group and a fluoxetinetreated group. The depression rat
      model was established under CUMS and seperated feeding, after which, open field,
      sugar consumption and forced swimming test were applied in the first group. After
      the blood was taken in the second group of rats through heart puncture, the level
      of serum Hcy was detected by enzymatic cycling assay and serum anti-CCP antibody
      by ELISA. RESULTS: Compared with the control group and the fluoxetine treatment
      group, spontaneous activity and sucrose consumption and preference percentage of
      the rats in the model group significantly reduced, while the immobility time in
      forced swimming test and the level of Hcy and anti-CCP antibody in the rat serum
      significantly increased. CONCLUSION: Immunity inflammation and autoimmune
      reaction exist in CUMS depression model rats, and fluoxetine treatment can
      improve these immune response.

PMID- 22954914
TI  - [Reduced expression and secretion of apolipoprotein M in fat-fed, streptozotocin
      diabetic rats is partially reversed by an artificial ligand of PPARgamma].
AB  - OBJECTIVE: To investigate the effect of administration of rosiglitazone, an
      artificial ligand of PPARgamma, on the expression and secretion of apolipoprotein
      (apoM) in fat-fed, streptozotocin-treated rats, an animal model for type 2-like
      diabetes. METHODS: Healthy male SD rats were divided into 4 groups: a control
      group (n=7), a high-fat chow group (HF group, n=8), a diabetes mellitus group (DM
      group, n=7), and a diabetes mellitus group with rosiglitazone intervention group
      (RSG group, n=7). Fasting blood glucose (FBG), fasting insulin (FINS),
      triglyceride (TG) and total cholesterol (TC) were measured at the beginning of
      the study. The diabetic rats model was established by feeding high fat chow and
      intraperitoneal injection of streprozotocin. Then the randomly selected treatment
      group was given rosiglitazone by daily gavage for 8 weeks. All the rats were
      killed at the fifteenth week, at which time blood and tissues (liver, kidney,
      adipose) were collected and prepared. The levels of FBG, FINS, TG and TC were
      assayed. The level of apoM in serum was measured by enzyme-linked immunosorbent
      assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used
      to determine apoM mRNA expression in liver, kidney, and adipose tissues. RESULTS:
      Compared with either control group or HF group, serum apoM concentration in the
      DM group was reduced significantly (P<0.05); compared with the DM group, however,
      serum apoM concentrations in RSG group were increased (P<0.05). The expression of
      apoM mRNA in liver was highest, in kidney medium, and in adipose tissue extremely
      low (P<0.05). ApoM mRNA expression in liver and kidney was decreased in both DM
      and HF groups compared to control group (P<0.05). But, as with serum apoM
      concentration, apoM mRNA in the liver, kidney and adipose tissues of the RSG
      group were all increased markedly (P<0.05). The level of serum apoM in SD rats
      correlated negatively with TG (r=-0.466, P=0.011), TC (r=-0.568, P= 0.001), FBS
      (r =-0.371, P<0.001), and FINS(r=-0.768, P= 0.048 ). CONCLUSION: These results
      suggest that apoM may participate in the glucose and lipid metabolism by the
      regulation of PPARgamma.

PMID- 22954915
TI  - [Prevalence of vitamin D deficiency and impact on quality of life in patients
      with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To survey the prevalence of vitamin D deficiency in patients with
      chronic obstructive pulmonary disease (COPD) and to determine the impact of
      vitamin D deficiency on the quality of life in COPD patients. METHODS: Thirty-six
      patients with acute exacerbations of COPD (AECOPD group), 38 outpatients with
      stable COPD (stable COPD group), and 30 healthy subjects (control group) in the
      Third Hospital of Changsha were enrolled in our study from Dec. 2011 to Mar.
      2012. The serum levels of 25-(OH)D were measured in all subjects by ELISA. The
      prevalence of vitamin D deficiency was calculated and compared among the 3
      groups. Scores of COPD assessment test (CAT) were measured and compared in the
      AECOPD group and the stable COPD group and the relation between 25-(OH)D and CAT
      scores was analyzed. RESULTS: 1) The levels of 25-(OH)D in the AECOPD group and
      the stable COPD group were significantly lower than those in the control group.
      The level of 25-(OH)D in the AECOPD group was significantly lower than that in
      the stable COPD group (P<0.05). 2) The prevalence of vitamin D deficiency was
      52.78% in the AECOPD group and that was 39.47% in the stable COPD group. The
      total prevalence of vitamin D deficiency was 45.95% in COPD patients. The
      prevalence of vitamin D deficiency was 16.67% in the control group. There was
      significant difference in the prevalence of vitamin D deficiency among the 3
      groups (P<0.05). 3) The prevalence of vitamin D deficiency in the AECOPD group
      was significantly higher than that in the control group (P<0.01) and the
      prevalence of vitamin D deficiency in the stable COPD group was significantly
      higher than that in the control group (P<0.05). There was no significant
      difference between the AECOPD group and the stable COPD group (P>0.05). 4)
      significant difference was found between the AECOPD group and the stable COPD
      group in CAT scores (P<0.01). 5) Both in the AECOPD group and the stable COPD
      group, the 25-(OH)D levels were negatively correlated with CAT scores (r=-0.603,
      P<0.01; r=-0.549, P<0.01, respectively). CONCLUSION: Vitamin D deficiency is
      highly prevalent in COPD patients. Vitamin D deficiency may have negative impact
      on the life quality in COPD patients.

PMID- 22954916
TI  - [Effect of gene GSTP1 silencing via shRNA transfection on androgen independent
      prostate cancer cell line Du145].
AB  - OBJECTIVE: To design short hairpin RNA (shRNA) interference sequence to silence
      glutathione S-transferase P1 (GSTP1) gene of androgen independent prostate cancer
      cell line DU145, and to explore its effect on proliferation and sensitivity to
      chemotherapeutics. METHODS: The target sequence was picked up to form the shRNA,
      and the 3 shRNA expression vectors were shRNA255, shRNA554 and shRNA593. The DNA
      template was cloned to plasmid pGPU6/GFP/Neo. The shRNA was identified by enzyme
      digesting and gene sequencing. The screening experiment was done to pick up the
      shRNA expression vector with the highest transfection ratio and best gene
      silencing results. DU145 cells were divided into a blank plasmid group and a
      shRNA transfected group. According to the chemotherapeutics the DU145 cells were
      divided into a fluorouracil (FU) group and a paclitaxel (PA) group, and the 2
      groups were subdivided into 4 subsets according to the chemotherapeutic
      concentrations (FU: 30, 60, 120, and 240 MUg/mL; PA: 0.2, 2, 10, and 20 MUg/mL),
      meanwhile a blank control group was included respectively. 3-(4,5-Dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate the
      proliferation after the transfection. MTT and terminal de-oxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) assay were used to detect the
      inhibition effect of different concentrations of 5-FU or PA on the proliferation
      and induction of apoptosis of DU145. RESULTS: The transfection ratio of the 3
      shRNA expression vectors (shRNA255, shRNA554, and shRNA593) was (63.30+/-1.04)%,
      (76.20+/-0.68)%, and (72.70+/-0.33)%, and the transfection ratio of shRNA554 was
      the highest. there was significant difference among the above 3 shRNA expression
      vectors (P<0.01). After the transfection, the mRNA was 128.31+/-2.50, 43.24+/
      4.30 and 85.62+/-6.30, the GSTP1 protein was 163.92+/-12.40, 65.38+/-9.30 and
      114.25+/-16.70. After the transfection of shRNA554, the mRNA and protein of GSTP1
      were the lowest level. there was significant difference among the above 3 shRNA
      expression vector (P<0.01). MTT analysis showed that before the transfection, the
      survival ratio of cells under different concentrations of FU (30, 60, 120, and
      240 MUg/mL) was (95.60+/-2.11)%, (90.20+/-0.86)%, (83.10+/-3.12)% and (74.60+/
      1.32)%; however after the transfection, the survival ratio of cells was (91.30+/
      1.43)%, (84.60+/-2.13)%, (73.20+/-1.52)%, and (65.5+/-0.942)%. TUNEL assay showed
      that before the transfection, the apoptosis ratio of cells under different
      concentrations of FU (30, 60, 120, and 240 MUg/mL) was (5.50+/-0.88)%, (10.20+/
      1.64)%, (15.20+/-2.39)%, and (25.10+/-2.59)%; however after the transfection, the
      apoptosis ratio of cells was (10.8+/-0.62)%, (15.7+/-1.32)%, (20.4+/-1.89)%, and
      (34.9+/-2.54)%. After the transfection, the cell survival ratio decreased under
      the same concentration of FU, and the apoptosis ratio increased, with statistical
      significance (both P<0.01). MTT analysis showed that before the transfection, the
      survival ratio of cells under different concentrations of PA (0.2, 2, 10, and 20
      MUg/mL) was (98.50+/-2.34)%, (95.20+/-1.32)%, (89.40+/-0.68)%, and (82.70+/
      1.73)%; after the transfection the survival ratio of cells was (94.20+/-0.78)%,
      (86.50+/-2.13)%, (78.70+/-1.34)%, and (70.10+/-0.76)%. TUNEL assay showed that
      before the transfection, the apoptosis ratio of cells under different
      concentrations of PA (0.2, 2, 10, and 20 MUg/mL) were (2.40+/-1.07)%, (5.20+/
      1.33)%, (10.50+/-2.41)%, (20.70+/-1.92)%; after the transfection the apoptosis
      ratio of cells was (5.46+/-2.13)%, (13.80+/-1.24)%, (21.20+/-2.39)%, and (29.20+/
      2.21)%. After the transfection, the cell survival ratio decreased under the same
      PA concentration, and the apoptosis ratio increased, with statistical
      significance (both P<0.01). CONCLUSION: gene GSTP1 silence via shRNA transfection
      to androgen independent prostate cancer cell line DU145 can inhibit its
      proliferation in time dependent manner, and induce apoptosis and raise its
      sensitivity to chemotherapeutics.

PMID- 22954917
TI  - [Multislice spiral computer tomography imaging characteristics of urachus
      lesions].
AB  - OBJECTIVE: To analyze the multislice spiral computer tomography (MSCT)
      manifestations and its value in the diagnosis of urachus lesions. METHODS: A
      total of 26 patients with urachus disease diagnosed by pathological examination
      in our hospital between October 2007 and May 2011 were included in this study. We
      retrospectively analyzed MSCT images on the size, location, and shape character
      of the foci, and the image features of Retzius space. RESULTS: In the group, 12
      patients had simple urachal cyst with homogeneous fluid filling the cavity with
      thin wall in CT scanning; five had infected urachal cyst with thickened and
      enhanced wall, some patch and strip appearing in Retzius space surrounding the
      lesion; two had infected urachal sinus, and another 3 had urachus leakage. Four
      had urachal tumor showing irregular cysticsolid mass over the apex of the bladder
      with apparent enhancement in contrast imaging, and 2 had calcification. Invasion
      of the bladder wall was found in 4 patients, extensive invasion of the ileum,
      rectum, uterus and retroperitoneal lymph nodes was found in 1. CONCLUSION: MSCT
      scan can demonstrate the location, shape, extent of the lesion as well as the
      relation with adjacent structures, thereby providing valuable information for the
      diagnosis and differential diagnosis of urachus lesions.

PMID- 22954918
TI  - [Percutaneous nephrolithotomy of staghorn calculi in patients by mini-tract and
      standard-tract].
AB  - OBJECTIVE: To compare the outcome of mini-tract vs standard-tract percutaneous
      nephrolithotomy (PCNL) in staghorn calculi. METHODS: Between May 2009 and May
      2011, 122 patients with renal staghorn calculi were treated by PCNL. Fifty-six
      patients underwent mini-PCNL and the others underwent standard-PCNL. The
      therapeutic effect and complication of the 2 groups were compared. RESULTS: The
      two groups had comparable demographic conditions. Although the operation time was
      significantly longer in mini-PCNL group [(126+/-24.5) min vs (98+/-18.9) min],
      there was no striking difference in hospital stay [(5.7+/-1.3) d vs (5.3+/-1.1)
      d], hemoglobin drop [(9.5+/-3.2) g/L vs (10.5+/-3.3) g/L], stone-free state
      before charge (91.1% vs 89.4%) and complications. CONCLUSION: The efficacy and
      safety of mini-PCNL and standard-PCNL are not significantly different.

PMID- 22954919
TI  - [Multi-frequency low-dose intravenous iron on oxidative stress in maintenance
      hemodialysis patients].
AB  - OBJECTIVE: To investigate the effect of different intravenous iron treatment
      regimens on anemia and oxidative stress in maintenance hemodialysis (MHD)
      patients. METHODS: A total of 58 MHD patients were randomly divided into a multi
      frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8
      weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose
      100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20).
      Another 20 healthy people served as a control group (n=20). The changes of
      hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation
      (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA),
      superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and
      after the treatment. RESULTS: After 8 weeks, compared with the non-iron group,
      the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly
      elevated (P<0.01), but there was no difference between the two iron groups
      (P>0.05). After the single dialysis, the two iron groups had higher level of
      serum MDA, MPO and lower level of serum SOD than that of the non-iron
      supplementation group (P<0.01). The multi-frequency low-dose intravenous iron
      group had lower level of serum MDA [(5.37 +/- 0.73) nmol/mL vs (6.37+/-1.67)
      nmol/mL], MPO [(81.41+/-7.60) U/L vs (96.75+/-16.97) U/L] and higher level of
      serum SOD [(84.77 +/- 14.02) U/mL vs (68.23 +/- 4.90) U/mL] than that of the less
      frequency regular-dose intravenous iron group. After 8 weeks, there was no
      significant difference between the two iron groups (P>0.05). CONCLUSION: Multi
      frequency low-dose intravenous iron can effectively improve anemia in MHD
      patients, whose acute oxidative stress is lower than that of less-frequency
      regular-dose intravenous iron, and is a relatively safe and effective intravenous
      iron treatment regimen.

PMID- 22954920
TI  - [Protective effect of SjC23-Hsp70 DNA vaccine and interleukin-12 on Schistosoma
      japonicum infection in water buffalos].
AB  - OBJECTIVE: To determine the immune-protective effect of Japan Schistosoma
      (Chinese mainland strain) 23 kD membrane protein-heat shock protein (SjC23-Hsp70)
      DNA vaccine plus adjuvantinduced interleukin-12 (IL-12) plasmid DNA on
      Schistosoma japonicum infection in water buffalos. METHODS: Forty-five health
      water buffalos (8-10 months old) in non-endemic area of schistosomiasis were
      randomly assigned into group A (SjC23-Hsp70+IL-12, 300 MUg), group B (SjC23+IL
      12, 300 MUg) and group C (pVAX+IL-12, 300 MUg), 15 in each group. Each buffalo
      was immuned by shoulder intramuscular injection for 3 times, at an interval of 28
      days. Twenty-eight days after the last immunization, each buffalo was infected
      with 1000 Japan cercariae of Schistosoma. Fecal examinations were conducted 2
      days and 1 day before the perfusion, and on the day of perfusion. The number of
      hatching miracidia and eggs per gram feces was recorded. Fifty-six days after the
      infection, the buffalos were sacrificed and perfused via the descending aorta.
      The recovered adult worms and eggs in the liver tissue were counted. RESULTS: We
      compared group A and B with group C: the estrogen reduction rate was 45.7% and
      26.61%; bug reduction rate was 44.51% and 25.84%; the fecal egg reduction rate
      was 41.1% and 31.63%; the miracidium reduction rate was 48.11% and 38.07%; and
      the liver egg reduction rate was 43.39% and 31.95%. The above rates in group A
      were higher than those in group B (P<0.05). CONCLUSION: SjC23-Hsp70 DNA vaccine
      combined with IL-12 may have a significant immunoprotective effect on buffalos.

PMID- 22954921
TI  - [Strengths and Difficulties Questionnaire in 737 primary and middle school
      students aged 6 -17 in Changsha].
AB  - OBJECTIVE: To explore the mental health condition of primary and middle school
      students in Changsha and to provide reference for future evaluation or
      intervention. METHODS: Strengths and Difficulties Questionnaire (SDQ) (the
      edition for parents) was used to investigate 737 primary and middle school
      students aged 6-17 in Changsha. RESULTS: The prevalence of difficulty was 14.11%.
      The males showed higher scores of problem, hyperactivity and impact, while the
      females scored higher in emotional symptom as well as prosocial behaviors.
      Students aged 11-13 and 14-17 showed higher scores of total difficulties, peer
      problems and emotional symptom than those aged 6-10. Apart from higher scores of
      total difficulties and peer problems, the other scores were similar to the normal
      scores in China. there was significant difference in the normal scores between
      china and other countries. CONCLUSION: mental health problems have divergent
      characters in gender and age. This study also highlights the importance of
      establishing local norms of SDQ and the need for appropriate measures in
      practical situations.

PMID- 22954922
TI  - [In vitro selection of single strand deoxyribonucleic acid aptamers binding to
      cells from patients with acute myeloblastic leukemia].
AB  - OBJECTIVE: To screen aptamers binding CD33+/CD34- cells from patients with acute
      myeloblastic leukemia M2 subtype (AML-M2). METHODS: CD33+/CD34- cells from
      patients with AML-M2 were taken as targeted cells, CD33+/ CD34- cells from normal
      people were taken as anti-selecting cells, and aptamers in the single strand
      deoxyribonucleic acid (ssDNA) library were then selected repeatedly by cell
      systematic evolution of ligands by exponential enrichment (C-SELEX) technology,
      and amplified by polymerase chain reaction (PCR) to generate sub-ssDNA library.
      During the experiment, PCR amplification with fluorescently labeled primer and
      flow cytometry were performed to analyze the aptamers'enrichment of sub-library,
      and the final round product of the sub-ssDNA library was cloned. After the
      sequencing, the primary and secondary structures of the aptamers were analyzed.
      RESULTS: Electrophoresis indicated that the product of PCR amplification for each
      round subssDNA library was able to see a clear DNA band in the agarose gel. After
      13 rounds of screening, the fluorescence intensity of the sub-ssDNA library
      binding the cells ranged from 2.14% to 51.12%, reaching a steady state at the
      13th round. A total of 30 clones were selected and sequenced, 22 of which
      contained 1 of the 4 conserved sequences of AAGTA, TATCT, AGATG and AAATT in
      their primary structure, but the remained eight aptamers contained none of the
      conserved sequence. Secondary structure analysis indicated that four stem-loops
      and loop simulation convex structures existed in the aptamers. CONCLUSION: C
      SELEX technology can be used to screen the aptamers binding primary cells from
      patients with leukemia. The aptamers selected from the CD33+/CD34- cells from the
      patients of AML-M2 subtype might be used for the diagnosis and treatment for
      leukemia.

PMID- 22954923
TI  - [Reasonable surgical approach for grade III cervical intraepithelial neoplasia].
AB  - OBJECTIVE: To analyze the clinical pathologic characteristics of cervical
      intraepithelial neoplasia grade III (CINIII ) and to explore optimal surgery for
      CINIII patients. METHODS: The clinical pathologic characteristics, surgical
      treatments, prognosis and history of 383 CINIII patients, who hospitalized from
      August 2005 to December 2010, were reviewed and analyzed. Among the patients, 213
      (55.6%) received cold-knife conization surgery and 170 (44.4%) received ordinary
      electric knife conization surgery. RESULTS: There was no significant statistic
      difference between cold-knife conization group and ordinary electric-knife
      conization group on the level of clearance of the pathologic tissues and the
      cervical cone diameter and cone high. Intraoperative blood loss was (13.1+/-5.2)
      mL and (25.5+/-17.2) mL. Bleeding of electric knife conization group, compared
      with that of the cold knife conization group, decreased by nearly 50%. The
      difference between the 2 groups was significant (P<0.01). Pathological
      examination after conization operation indicated that 350 out of the 383 patients
      didn't show pathological upgrade while 33 patients showed pathological
      development, among which 21 were diagnosed with invasive cervical cancer at Ia1
      clincal stage, 7 atIa2 clincal stage and 5 atIb1 clincal stage. In 3 cases
      (14.3%) Ia1 cervical cancer patients, fertility requirements and negative margins
      with cervical conization were closely followed up, and one patient (4.8%) with
      positive margin and fertility requirements had re-conecut. The remaining 17
      (80.9%) had resected the uterus outside the fascia (or plus attachments) . All
      the 12 patients with invasive cervical cancer at Ia2 orIb1 clinical stage
      received radical hysterectomy. No tumor recurrence was observed in the 383
      patients. CONCLUSION: Treatment optimazation of CINIII patients should be based
      on clinical pathological diagnosis and individual requirements. Both cervical
      conization surgery and total hysterectomy have been proved safe and practical for
      CINIII patients.

PMID- 22954924
TI  - [Impact of renal denervation on expression of renalase and tyrosine hydroxylase
      in adult rats with spontaneous hypertension].
AB  - OBJECTIVE: To investigate the impact of renal denervation on the blood pressure,
      plasma renalase content and expression of renalase and tyrosine hydroxylase (TH)
      in the idney of spontaneous hypertensive (SH) rats and to explore the role of
      renal denervation in lowering the blood pressure. METHODS: SH rats were randomly
      assigned into a baseline group, a surgery (renal denervation) group, a sham group
      and a control group (n=48). WKY rats matched in age (n=12) served as a baseline
      control group. All rats were housed until 12 weeks old. Then, the rats in the
      baseline group and the WKY group were sacrificed whose blood and kidney were
      collected for examination. In the renal denervation group, the sham group and the
      control group, the blood pressure was monitored continuously. One week and 6
      weeks after the renal denervation, 6 rats in each group were sacrificed whose
      blood and kidney were collected. ELISA was employed to measure the plasma
      renalase and Western blot assay done to detect the expression of TH and renalase
      in the kidney. RESULTS: Compared with WKY rats, blood pressure significantly
      increased and TH protein expression markedly elevated (P<0.05) in SH rats in the
      baseline group, but plasma renalase content and protein expression of renalase in
      the kidney dramatically reduced (P<0.05). One week after the surgery, the mean
      arterial pressure and TH protein expression in the surgery group were lowered
      compared with the baseline group and dramatically reduced compared with the sham
      group and the control group (P<0.05). In the surgery group, the renalase level
      was markedly increased compared with the baseline group, the sham group, and the
      control group (P<0.05). Six weeks after the renal denervation, the mean arterial
      pressure and TH level in the surgery group were significantly increased but the
      renalase content and expression markedly reduced compared with those 1 week, but
      there were no marked differences among the surgery group, the sham group, and the
      control group (P>0.05). No pronounced differences in the above variables were
      found between the sham group and the control group at any time point (P>0.05).
      CONCLUSION: Renal denervation can lower the blood pressure, which may attribute
      to the suppression of sympathetic nerves, increase in plasma renalase content and
      renalase expression in the kidney.

PMID- 22954925
TI  - Use of fluorescein angiography in the diagnosis and management of uveitis.

PMID- 22954926
TI  - Use of indocyanine green angiography in uveitis.

PMID- 22954927
TI  - Use of optical coherence tomography in the diagnosis and management of uveitis.

PMID- 22954928
TI  - Use of fundus autofluorescence in the diagnosis and management of uveitis.

PMID- 22954929
TI  - Imaging methods for inflammatory macular edema.
AB  - OCT has become the most common way to image ME. It represents morphologic
      characteristics of ME in detail, allows the quantitative measurements of ME, and
      depicts the integrity of the photoreceptor layer important for the visual
      prognosis and further evaluates the otherwise invisible changes of the
      vitreoretinal interface. Normative data for the different devices are scarce and
      data from different devices cannot be compared. FA retains its crucial role in
      determining the activity of the uveitis and also forms an important diagnostic
      tool. OCT and FA imaging in inflammatory ME are complementary methods, each with
      its specific indications and outcomes. Ultrahigh-resolution OCT's will bring a
      further understanding of the pathogenesis of inflammatory ME.

PMID- 22954930
TI  - Imaging the choroid in uveitis.

PMID- 22954931
TI  - Imaging retinal vascular changes in uveitis.

PMID- 22954932
TI  - Imaging in the diagnosis and management of ocular tuberculosis.

PMID- 22954933
TI  - The role of imaging in the diagnosis and management of ocular sarcoidosis.

PMID- 22954934
TI  - Imaging syphilis uveitis.

PMID- 22954935
TI  - Imaging in ocular toxoplasmosis.

PMID- 22954936
TI  - Imaging in the diagnosis and management of ocular toxocariasis.

PMID- 22954937
TI  - Imaging in the diagnosis and management of ocular cat scratch disease.

PMID- 22954938
TI  - Imaging in the diagnosis and management of Vogt-Koyanagi-Harada disease.

PMID- 22954939
TI  - Imaging for sympathetic ophthalmia:  impact on the diagnosis and management.

PMID- 22954940
TI  - Imaging in the diagnosis and management of Behcet disease.

PMID- 22954941
TI  - Imaging in birdshot chorioretinopathy.

PMID- 22954942
TI  - The use of imaging in the diagnosis and management of intraocular lymphoma.

PMID- 22954943
TI  - Imaging in the diagnosis and management of APMPPE.

PMID- 22954944
TI  - Multiple evanescent white dot syndrome (MEWDS).

PMID- 22954945
TI  - Imaging in the diagnosis and management of serpiginous choroiditis.

PMID- 22954946
TI  - Relentless placoid chorioretinitis.

PMID- 22954947
TI  - Imaging in the diagnosis and management of multifocal choroiditis and punctate
      inner choroidopathy.

PMID- 22954948
TI  - Imaging in the diagnosis and management of acute zonal occult outer retinopathy.

PMID- 22954949
TI  - Imaging in the diagnosis and management of acute idiopathic maculopathy.

PMID- 22954950
TI  - Imaging in the diagnosis and management of acute macular neuroretinopathy.

PMID- 22954951
TI  - Imaging in the diagnosis and management of idiopathic retinal vasculitis,
      aneurysms, and neuroretinitis (IRVAN).

PMID- 22954952
TI  - Imaging in the diagnosis and management of diffuse unilateral subacute
      neuroretinitis.

PMID- 22954954
TI  - Imaging in the diagnosis and management of uveitis. Preface.

PMID- 22954955
TI  - Diagnosis and management of sudden death in children.
AB  - PURPOSE OF REVIEW: Sudden death is a leading cause of death in industrialized
      nations. Sudden death in children represents a relatively small proportion of
      sudden death in the population, but has devastating effects on families and
      communities, and often attracts significant attention. RECENT FINDINGS: Several
      recent studies show that a portion of previously unexplained sudden death in
      children is due to cardiac conditions which are potentially identifiable by
      'molecular autopsy' or investigation of family members. As some of these
      conditions that may present with sudden death can be detected by ECG, the
      controversial role of screening asymptomatic children will be discussed, as will
      the question of increased risk associated with stimulant medications. Recent
      pharmacologic and nonpharmacologic advancements for those with identifiable
      conditions at increased risk of sudden death will be reviewed. SUMMARY: Recent
      developments have refined our understanding of the various causes of sudden death
      in children. Post-mortem genetic testing and/or investigation of family members
      can be fruitful in determining a cause and identifying at-risk relatives. Given
      the available and potential treatments for specific disorders with increased risk
      of sudden death, the benefit of identifying such disorders early is clear. The
      debate regarding universal ECG screening is social and political, as well as
      scientific.

PMID- 22954956
TI  - Adolescent STIs for primary care providers.
AB  - PURPOSE OF REVIEW: Sexually transmitted infections (STIs) remain a significant
      source of morbidity among adolescents, who bear a disproportionate burden of
      disease. Many infections are asymptomatic, but pose significant risk for long
      term sequelae in this at-risk population. RECENT FINDINGS: Recommendations
      published within the last 5 years from the Centers for Disease Control, United
      States Preventive Services Task Force, and American Academy of Pediatrics are
      available to aid providers in appropriate screening, treatment, and prevention of
      common STIs. However, recent data indicate that many adolescents at risk for STIs
      are not being appropriately screened. In this review, we summarize screening and
      treatment recommendations for chlamydia and gonorrhea; prevention and screening
      recommendations for human papilloma virus (HPV); and appropriate testing for HIV
      and syphilis. SUMMARY: Primary care providers are in a unique position to address
      STIs with adolescents. Improved adherence to screening, treatment, and
      vaccination recommendations by primary care providers is imperative to reduce
      prevalence, complications, and transmission of STIs in the adolescent population.

PMID- 22954957
TI  - Bibliography. Cardiovascular medicine (CM). Current world literature.

PMID- 22954959
TI  - The PhenX Toolkit pregnancy and birth collections.
AB  - PURPOSE: Pregnancy and childbirth are normal conditions, but complications and
      adverse outcomes are common. Both genetic and environmental factors influence the
      course of pregnancy. Genetic epidemiologic research into pregnancy outcomes could
      be strengthened by the use of common measures, which would allow data from
      different studies to be combined or compared. Here, we introduce perinatal
      researchers to the PhenX Toolkit and the Collections related to pregnancy and
      childbirth. METHODS: The Pregnancy and Birth Collections were drawn from measures
      in the PhenX Tooklit. The lead author selected a list of measures for each
      Collection, which was reviewed by the remaining authors and revised on the basis
      of their comments. We chose the measures we thought were most relevant for
      perinatal research and had been linked most strongly to perinatal outcomes.
      RESULTS: The Pregnancy and Birth Health Conditions Collection includes 24
      measures related to pregnancy and fertility history, maternal complications, and
      infant complications. The Pregnancy and Birth Outcome Risk Factors Collection
      includes 43 measures of chemical, medical, psychosocial, and personal factors
      associated with pregnancy outcomes. CONCLUSIONS: The biological complexity of
      pregnancy and its sensitivity to environmental and genomic influences suggest
      that multidisciplinary approaches are needed to generate new insights or
      practical interventions. To fully exploit new research methods and resources, we
      encourage the biomedical research community to adopt standard measures to
      facilitate pooled or meta-analyses.

PMID- 22954960
TI  - Alanine transaminase has opposite associations with death from diabetes and
      ischemic heart disease in NHANES III.
AB  - PURPOSE: Diabetes increases the risk of ischemic heart disease (IHD). Stringent
      control of diabetes does not reliably reduce cardiovascular events. Some global
      regions, such as East Asia, have low mortality rates from IHD and high rates of
      diabetes. We hypothesized that some aspects of liver function might underlie this
      paradox. METHODS: We used multivariable proportional hazards regression in 16,865
      adults from the National Health and Nutrition Examination Survey (NHANES) III
      (1988-1994) followed until December 31, 2006, to assess the adjusted associations
      of gender-specific tertiles of alanine transaminase (ALT), as a marker of
      hepatocellular damage, and bilirubin (BIL), as a marker of other aspects of liver
      function, with death from diabetes (n = 132), IHD related to diabetes (n = 153),
      and IHD unrelated to diabetes (n = 921). RESULTS: ALT was positively associated
      with death from diabetes (hazard ratio [HR], 2.17; 95% confidence interval [CI],
      1.19-3.98 for high compared with low ALT tertile) and IHD related to diabetes
      (HR, 2.14; 95% CI, 1.07-4.31), but negatively associated with IHD unrelated to
      diabetes (HR, 0.76; 95% CI, 0.58-0.98) adjusted for age, gender, education,
      race/ethnicity, smoking, and alcohol use. BIL had no such associations.
      CONCLUSIONS: ALT may be a marker of an underlying etiology relating to the
      paradoxical associations of diabetes and IHD at a population level.

PMID- 22954961
TI  - Faculty and staff development strategies to prevent childhood obesity.
AB  - Childhood obesity prevention and management is currently a priority health focus
      in the United States. Graduates of nursing programs and practicing registered
      nurses must be competent to implement interventions and programs to assess,
      prevent, and manage childhood obesity in acute care and community settings. This
      article provides an overview of the scope of the problem and recommendations from
      relevant health organizations. Nurse and staff educators are provided with
      specific content and teaching strategies for the prevention and management of
      childhood obesity for developing the knowledge and skills of nursing students,
      staff nurses, and advanced practice nurses.

PMID- 22954963
TI  - Early transcriptional targets of MyoD link myogenesis and somitogenesis.
AB  - In order to identify early transcriptional targets of MyoD prior to skeletal
      muscle differentiation, we have undertaken a transcriptomic analysis on gastrula
      stage Xenopus embryos in which MyoD has been knocked-down. Our validated list of
      genes transcriptionally regulated by MyoD includes Esr1 and Esr2, which are known
      targets of Notch signalling, and Tbx6, mesogenin, and FoxC1; these genes are all
      are known to be essential for normal somitogenesis but are expressed surprisingly
      early in the mesoderm. In addition we found that MyoD is required for the
      expression of myf5 in the early mesoderm, in contrast to the reverse relationship
      of these two regulators in amniote somites. These data highlight a role for MyoD
      in the early mesoderm in regulating a set of genes that are essential for both
      myogenesis and somitogenesis.

PMID- 22954962
TI  - Env sequence determinants in CXCR4-using human immunodeficiency virus type-1
      subtype C.
AB  - HIV-1 subtype C (HIV-1C) CXCR4-using virus is isolated infrequently and is poorly
      characterized. Understanding HIV-1C env characteristics has implications for the
      clinical use of antiretrovirals that target viral entry. A total of 209 env
      clones derived from 10 samples with mixed CCR5-(R5), CXCR4-using (X4) or dual
      tropic HIV-1C were phenotyped for coreceptor usage. Intra-patient X4 and R5
      variants generally formed distinct monophyletic phylogenetic clusters. X4
      compared to R5 envs had significantly greater amino acid variability and
      insertions, higher net positive charge, fewer glycosylation sites and increased
      basic amino acid substitutions in the GPGQ crown. Basic amino acid substitution
      and/or insertion prior to the crown are highly sensitive characteristics for
      predicting X4 viruses. Chimeric env functional studies suggest that the V3 loop
      is necessary but often not sufficient to impart CXCR4 utilization. Our studies
      provide insights into the unique genotypic characteristics of X4 variants in HIV
      1C.

PMID- 22954965
TI  - Novel affinity purification of xanthine oxidase from Arthrobacter M3.
AB  - An affinity protocol for purification of xanthine oxidase (XOD) from Arthrobacter
      M3 was developed. The isolation procedure consisted of only three steps, ammonium
      sulfate precipitation, affinity extraction to exclude the major impurities, and
      the final refining procedure with DEAE ion-exchange chromatography for removal of
      minor contaminants. In this affinity preparation, guanine, an analogue of
      xanthine, was chosen as the affinity ligand, and was coupled with Sepharose 4B
      through spacers composed of epichlorohydrin and ethylenediamine. Crude protein
      has been run through ammonium sulfate precipitation and the affinity column,
      99.1% of proteins were removed. After DEAE ion-exchange chromatography, the
      purity of the refined XOD was 97.5% by Native-PAGE analysis. The activity
      recovery of purified XOD (36.1%) was almost higher than that of other methods
      reported. Reducing SDS-PAGE analysis showed that the purified XOD (one band in
      Native-PAGE analysis) showed two polypeptides with the molecular weights ~35kDa
      and ~100kDa, respectively. The desorption constant K(d) and the theoretical
      maximum absorption Q(max) on the affinity medium were 3.0MUg/ml and 2.2mg/g
      medium in absorption analysis.

PMID- 22954964
TI  - Signaling by FGF4 and FGF8 is required for axial elongation of the mouse embryo.
AB  - Fibroblast growth factor (FGF) signaling has been shown to play critical roles in
      vertebrate segmentation and elongation of the embryonic axis. Neither the exact
      roles of FGF signaling, nor the identity of the FGF ligands involved in these
      processes, has been conclusively determined. Fgf8 is required for cell migration
      away from the primitive streak when gastrulation initiates, but previous studies
      have shown that drastically reducing the level of FGF8 later in gastrulation has
      no apparent effect on somitogenesis or elongation of the embryo. In this study,
      we demonstrate that loss of both Fgf8 and Fgf4 expression during late
      gastrulation resulted in a dramatic skeletal phenotype. Thoracic vertebrae and
      ribs had abnormal morphology, lumbar and sacral vertebrae were malformed or
      completely absent, and no tail vertebrae were present. The expression of Wnt3a in
      the tail and the amount of nascent mesoderm expressing Brachyury were both
      severely reduced. Expression of genes in the NOTCH signaling pathway involved in
      segmentation was significantly affected, and somite formation ceased after the
      production of about 15-20 somites. Defects seen in the mutants appear to result
      from a failure to produce sufficient paraxial mesoderm, rather than a failure of
      mesoderm precursors to migrate away from the primitive streak. Although the
      epiblast prematurely decreases in size, we did not detect evidence of a change in
      the proliferation rate of cells in the tail region or excessive apoptosis of
      epiblast or mesoderm cells. We propose that FGF4 and FGF8 are required to
      maintain a population of progenitor cells in the epiblast that generates mesoderm
      and contributes to the stem cell population that is incorporated in the tailbud
      and required for axial elongation of the mouse embryo after gastrulation.

PMID- 22954967
TI  - Simultaneous determination of azelastine and its major metabolite
      desmethylazelastine in human plasma using high performance liquid chromatography
      tandem mass spectrometry.
AB  - A selective and sensitive high performance liquid chromatography-tandem mass
      spectrometric method was developed for the analysis of azelastine and its major
      metabolite, desmethylazelastine, in human plasma. Azelastine-(13)C, d(3) was used
      as internal standard. Azelastine, desmethylazelastine and the internal standard
      were extracted by a liquid-liquid extraction method and separation was performed
      under isocratic chromatographic condition. An abnormal signal loss issue for
      desmethylazelastine during method development was investigated and resolved. The
      developed method was precise and reproducible as shown by good intraday assay and
      interday assay precision (CV%<= 12.8%). The calibration curve was linear over a
      range of 10.0/10.0-1000/200 pg/mL for azelastine/desmethylazelastine. The method
      was successfully applied to a pilot bioequivalence study subsequently.

PMID- 22954966
TI  - Development of a sensitive HPLC method to measure in vitro permeability of E- and
      Z-isomeric forms of thiosemicarbazones in Caco-2 monolayers.
AB  - In the current study, we developed a HPLC method to quantitatively measure the
      permeability of the BpT-based chelators, 2-benzoylpyridine 4-ethyl-3
      thiosemicarbazone (Bp4eT) and 2-benzoylpyridine 4-allyl-3-thiosemicarbazone
      (Bp4aT), across human colorectal adenocarcinoma (Caco-2) monolayers as a model of
      gut absorption. In aqueous solution, Bp4eT and Bp4aT formed inter-convertible Z
      and E isomers that were resolved by HPLC. Peak area was linear with respect to
      chelator concentration. Acceptable within-day and between-day precision (<22%)
      and accuracy (85-115% of true values) were obtained over a range of 1.0-100MUM
      for Bp4eT and 1.5-300MUM for Bp4aT. Limits of detection were 0.3MUM and 1MUM for
      Bp4eT and Bp4aT, respectively, while corresponding limits of quantification were
      1MUM and 5MUM. Both chelators showed significant ability to chelate iron in THP-1
      cells using a calcein-based assay and no apparent cytotoxicity was observed
      within 24h. Ratios of the apical to basolateral and basolateral to apical
      transport for Bp4eT were 1.10 and 0.89 at 100MUM and 300MUM respectively,
      indicating equal bi-directional movement of the compounds. Similarly, ratios were
      0.77 and 0.92 for Bp4aT, respectively. This study demonstrates that Bp4eT and
      Bp4aT can be efficiently transported through Caco-2 cells and can potentially be
      formulated for oral delivery.

PMID- 22954968
TI  - Development and validation of a rapid capillary zone electrophoresis method for
      determining charge variants of mAb.
AB  - This work aimed to develop a rapid capillary zone electrophoresis (CZE) method to
      provide abundant purity and identity information of monoclonal antibodies. The
      CZE running buffer system was optimized to be 20mM acetate-acetic acid (pH 6.0)
      together with the co-addition of 0.3% polyethylene oxide (PEO) and 2mM
      triethylenetetramine (TETA), which was further tested with advantages on the peak
      resolution improvements. The conditioning period was scheduled to 1 min for both
      0.1M HCl and CZE running buffer to reduce total separation time. Additionally,
      the applied voltage and effective separation length were optimized at 30 kV and
      20 cm separately. Compared with the method reported by Yan [1], this newly
      developed method showed a higher resolution in separating the two unknown basic
      peaks by testing monoclonal antibody sample (mAb1). The further validation
      results showed that for all five of charge isoform peaks of test mAb1,
      repeatability, intraday and interday precision had a RSD less than 0.58% for
      migration time and less than 3.18% for corrected area percent. The correlation
      coefficients of more than 0.98 for all peaks also demonstrated the good linearity
      for the method. In addition to the application of distinguishing intact antibody
      from C-terminal Lys variants, the method also has advantage in separating the
      Fab, Fc and intact antibody-relevant substances quickly, which facilitated the
      rough evaluation of papain induced digestion.

PMID- 22954970
TI  - Intravenous thrombolysis in acute ischemic stroke in the elderly.

PMID- 22954971
TI  - Efficacy and safety of thrombolysis in patients aged 80 years or above with major
      acute ischemic stroke.
AB  - BACKGROUND: Elderly patients with major ischemic strokes may remain severely
      disabled or dead. However, efficacy and safety of thrombolysis in this have not
      been fully explored. MATERIALS AND METHODS: Data from the case records of
      patients aged >80 years with acute ischemic stroke with admission National
      Institute of Health Stroke Scale (NIHSS) score >=10 admitted between April 2009
      and May 2011 were retrieved. Outcomes in patients treated with thrombolysis and
      control subjects were compared. Primary outcome was 3-month modified Rankin Scale
      (mRS) score 0-2. Secondary outcomes were 3-month mRS score 0-3, mRS score 5-6,
      mortality, and improvement NIHHS score at discharge. Safety outcome was
      hemorrhagic transformation. RESULTS: Study subjects included 22 patients treated
      with thrombolysis and 23 controls not treated with thrombolysis. Age, stroke
      severity, and proportion of identified major vessel occlusions were the variables
      for comparison between the two groups. More patients in the thrombolyzed group
      had mRS 0-2 outcome than in non-thrombolyzed group (18.2% vs. 0%; P = 0.049).
      Proportion of patients with mRS 0-3 outcome was also higher in thrombolyzed group
      than in non-thrombolyzed group (22.7% vs. 0%; P = 0.022). Patients in the
      thrombolyzed group had higher mortality, non-significant when compared to
      patients in the non-thrombolyzed group (18.2% vs. 8.7%; P = 0.414). However,
      lesser number of patients in the thrombolyzed group had mRS 5-6 outcome (35% vs.
      65%; P = 0.075). Median improvement in NIHSS score at discharge also showed a
      more favorable trend in thrombolyzed group (10 vs. 2; P = 0.082). Rates of
      symptomatic and asymptomatic hemorrhagic transformations in thrombolyzed group
      were 4.5% and 27.3% respectively. CONCLUSION: For elderly patients with major
      ischemic strokes, thrombolysis offers a greater chance of functional
      independence.

PMID- 22954972
TI  - Lateral ventricular subependymomas: An analysis of the clinical features of 27
      adult cases at a single institute.
AB  - OBJECTIVE: To evaluate the unique clinical characteristics and management of
      lateral ventricular subependymomas (LVSs). Patients and Methods : The case
      records of 27 adult consecutive patients with LVS admitted between March 1996 and
      May 2011 were reviewed. The relevant clinical data (including patient age and
      sex, neuroimaging studies, surgical records and follow up) were collected through
      a chart review. Patient neurological status was recorded using the Karnofsky
      Performance Scale (KPS). RESULTS: The gender distribution was 14:13 and the age
      from 33 to 66 years (median 45 years) at the time of operation. Headache and
      dizziness were the most common initial symptoms (17/27). Most of these tumours
      were located at the foramen of Monro (12/27). Magnetic resonance imaging (MRI)
      (21/27) showed well circumscribed tumours with cystic changes (21/27). The
      lesions were hypointense on T1-weighted images (19/21), hyperintense on T2
      weighted images (21/21), and contrast enhancement was no or minimal (19/21).
      Gross total resection was performed in 23 patients. Five patients required a
      ventriculo-peritoneal shunt because of postoperative hydrocephalus. The follow-up
      period ranged from 6 to 188 months (mean 55.5 months). No recurrence was observed
      during the follow up. CONCLUSION: In this study LVSs had equal gender
      distribution. Tumours around the foramen of Monro were the candidates for
      aggressive treatment; surgery was the best curative treatment; postoperative
      hydrocephalus should be attended to.

PMID- 22954973
TI  - The transylvian trans-insular approach to lateral thalamic lesions.
AB  - BACKGROUND: Thalamic tumors are rare intracranial tumors. The most common
      approaches to the thalamus have been directed through the ventricular system,
      which surrounds it. The transsylvian trans-insular approach to the lateral
      thalamus has been infrequently described probably because of the vulnerability of
      the internal capsule, which skirts this part of the thalamus. AIMS: To describe
      the approach emphasizing its anatomical basis and also to evaluate its safety and
      efficacy. SETTINGS AND DESIGN: Retrospective study conducted at a tertiary
      hospital. MATERIALS AND METHODS: Patient population included all the patients who
      underwent surgery for the lesions in lateral thalamus using the transylvian trans
      insular approach between 2005 and 2011. A trephine craniotomy was made, centered
      over posterior sylvian fissure and the surgical corridor was developed through
      the insular cortex. RESULTS: During the study period 10 patients (7 tumors and
      inflammatory lesions and 3 hypertensive bleeds) were treated using this approach.
      One peri-operative mortality was noted. In patients with lesions other than
      hypertensive thalamic hemorrhage, there was no postoperative worsening of
      neurological deficit as comparative to preoperative deficits. Total
      excision/evacuation of the lesion could be accomplished in all the patients.
      CONCLUSIONS: The transylvian trans-insular approach is safe, effective,
      anatomical procedure, and can be performed at a peripheral center without the
      need for navigation and intra-operative monitoring.

PMID- 22954974
TI  - Pituitary dysfunction in survivors of spontaneous subarachnoid hemorrhage of
      anterior communicating artery and middle cerebral artery aneurysms: A comparative
      study.
AB  - BACKGROUND: The data on incidence of hypopituitarism after SAH are conflicting.
      Furthermore, it is still not known whether there is any difference in hormonal
      deficiencies between SAH due to anterior communicating artery (A-com) and middle
      cerebral artery (MCA) aneurysms. MATERIALS AND METHODS: This study includes both
      retrospective and prospective arms. The data collected included baseline
      demographic profile, clinical severity on admission to the hospital by the Hunt
      and Hess grading system and World Federation of Neurological Surgeons (WFNS)
      grading, radiological severity of bleed by the Fisher's classification, and
      treatment details. All the patients underwent detailed hormonal evaluation at
      baseline and 6 months in prospective group while at the end of 1 year in the
      retrospective group. Hormonal deficiencies between patients with A-com and MCA
      aneurysmal SAH were compared using appropriate statistical tests. RESULTS: Of 60
      patients studied, 47 patients (A-com: 28 and MCA: 19) were in the retrospective
      group, while 13 patients (A-com-9, MCA-4) were in the prospective group. The
      baseline data were comparable between the two groups. At or after 6 months follow
      up, 19 (31.6%) patients, 10 patients with A-com and 9 patients with MCA
      aneurysmal SAH, had some form of hormone deficiency. Furthermore, there was no
      difference in endocrine dysfunctions between the two groups. There was no
      correlation between the severity of hormonal deficiency and the clinical severity
      of SAH grade by Hunt and Hess and radiological grade of SAH by Fisher's grade.
      CONCLUSION: Hormonal deficiencies are not uncommon in patients with SAH. There is
      no difference in hormonal deficiencies and severity of hypopituitarism in
      patients with SAH due to A-com and MCA bleed.

PMID- 22954975
TI  - Mechanical thrombectomy for acute ischemic stroke: The road thus far.
AB  - Early restoration of flow to perfuse the salvageable brain tissue in acute
      ischemic stroke significantly reduces mortality and morbidity. Recanalization of
      large vessel occlusions has not been more than 10-20% with intravenous
      thrombolysis. Use of mechanical devices in acute ischemic stroke has shown
      promise in greater recanalization rates and hopefully will yield more optimal
      stroke outcomes. The results of the recent trials appear promising as the devices
      continue to evolve, become more operator friendly, and patient outcomes improve.

PMID- 22954976
TI  - Safety and efficacy of mechanical thrombectomy with the Solitaire device in large
      artery occlusion.
AB  - BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator (TPA) has
      limited efficacy in proximal large vessel occlusions. This study was to assess
      the safety and efficacy of mechanical thrombectomy with a retrievable Solitaire
      stent in acute large artery occlusions . MATERIALS AND METHODS: This is a single
      center study enrolling patients treated with Solitaire-assisted thrombectomy
      between November 2010 and March 2011. Inclusion criteria were severe stroke of
      National Institutes of Health Stroke Scale (NIHSS) score >=10, treatment
      initiation within 6 hours from onset, and an angiographically verified occlusion
      of proximal middle cerebral artery (MCA) or internal carotid artery (ICA). The
      primary outcome was recanalization defined as Thrombolysis in Cerebral Infarct
      (TICI) reperfusion grade 2b/3. Secondary outcomes were good functional outcome at
      3 months (modified Rankin Scale [mRS] <=2), early substantial neurological
      improvement (NIHSS score improvement >=8 at 24 hours), and symptomatic
      hemorrhagic transformation (SHT). RESULTS: Ten patients were consecutively
      enrolled: Age: 72.4 ? 5.7 years; female: 70%; baseline median NIHSS score: 19.5;
      and ICA occlusion in 50% and M1 portion of MCA occlusion in 50%. Six patients
      received intravenous TPA before intra-arterial treatment, and five patients were
      treated with adjuvant intra-arterial urokinase. Successful recanalization was
      achieved in 7 (70%) patients. Four (40%) patients had a good functional outcome
      at 3 months, and three (30%) patients had an early substantial neurological
      improvement. SHT occurred in two patients (20%), and 3-month mortality rate was
      30%. There was no procedure-related complication. CONCLUSIONS: Mechanical
      thrombectomy with the Solitaire device can effectively recanalize proximal large
      vessel occlusions, and potentially improves clinical outcome.

PMID- 22954977
TI  - Stand alone mechanical thrombectomy (with penumbra system) for acute ischemic
      stroke based on MR imaging: Single center experience.
AB  - BACKGROUND: There is dismal rate of recanalization following intravenous
      thrombolysis of large vessel occlusive ischemic stroke. Trials on use of
      mechanical clot retrievers in acute ischemic stroke have used time from onset and
      clinical deficit at presentation as the main indications for intervention.
      MATERIALS AND METHODS: Retrospective analysis of case records of acute stroke
      seen between May 2009 and October 2011 was done. It revealed 23 patients with
      acute ischemic stroke treated by mechanical thrombectomy using Penumbra system
      (PS). We used magnetic resonance (MR) imaging in correlation with clinical
      presentation to determine patients likely to benefit from recanalization and
      accordingly offered or at times deferred revascularization. A comparison of
      approach and outcomes was done with other relevant trials/reports. RESULTS:
      Recanalization was achieved in all but one patient. Median modified Rankin Scale
      (mRS) score at 90 days was 2. Good clinical outcome (mRS <= 2) was achieved in
      56.5% compared with 25% in Penumbra pivotal trial and 36% in multi Mechanical
      Embolus Removal in Cerebral Ischemia (multi MERCI) trial. All cause mortality was
      13.04%. Symptomatic intracerebral hemorrhage (ICH) occurred in two patients
      (8.6%). CONCLUSION: Analysis of our results suggests that PS is safe and
      effective (91.3%) in recanalizing cerebral vessels without concomitant
      thrombolytics.

PMID- 22954978
TI  - Open surgical disconnection for congenital, multi-hole, pial arteriovenous
      fistulae in non-eloquent cortex.
AB  - Intracranial pial arteriovenous fistulae (pAVFs), a direct shunt between a
      feeding artery and a venous channel with the absence of a true nidus
      characteristic of other types of arteriovenous malformations, are rare. We report
      a seven-year-old girl with an incidental intracranial pAVF. Following partial
      embolization with a combination of platinum coils and liquid embolic material,
      this lesion was surgically disconnected and a definitive cure was achieved. Based
      on the particular characteristics of this lesion-multiple, small arterial
      feeders, superficial location, and proximity to the non-eloquent cortex-we feel
      this vascular lesion represents a subset of pAVFs that may be most reasonably and
      safely treated by open surgery. While staged embolization has recently gained
      popularity as a treatment option, the additive risk of multiple embolizations as
      well as repeated exposure to ionizing radiation should not be understated,
      especially in the pediatric population. Furthermore, given the paucity of data on
      the long-term effectiveness of embolization, surgery remains an elegant and
      durable treatment option for pAVFs in carefully selected patients.

PMID- 22954979
TI  - Brainstem hemorrhage following clipping of anterior communicating aneurysm: Is
      lumbar drain responsible?
AB  - Remote brainstem hemorrhage is an extremely rare complication following
      supratentorial surgery. We describe here a 55-year-old patient with ruptured
      anterior communicating artery aneurysm, who underwent an uneventful clipping of
      the aneurysm, and had a lumbar drainage intra-operatively to facilitate brain
      relaxation. In the postoperative period, he developed pontomesencephalic
      hemorrhage, and had a fatal outcome. The potential causative factors are
      discussed, and the relevant literature reviewed. This is probably the first
      reported case of this complication in the literature.

PMID- 22954980
TI  - Room tilt illusion in superior cerebellar artery stroke: Are we missing the
      classical neurological examination?

PMID- 22954981
TI  - Hypertrophic pachymeningitis and cerebral infarction resulting from ANCA
      associated vasculitis.

PMID- 22954982
TI  - Central pontine and extrapontine myelinolysis: Diffusion weighted imaging and
      diffusion tensor imaging on follow-up.

PMID- 22954983
TI  - A rare occurrence of concordant neural tube defects in monozygotic twins of an
      epileptic woman.

PMID- 22954984
TI  - Familial amyloid neuropathy: Unusual etiology in clinical practice.

PMID- 22954985
TI  - Hamstring lump in two muscular dystrophies: A novel observation.

PMID- 22954986
TI  - Hypocalcemia: A rare cause of epilepsia partialis continua.

PMID- 22954987
TI  - Guillain-Barre syndrome as a complication of typhoid fever in a child.

PMID- 22954988
TI  - Non filling of scalp arteriovenous malformation: Effect of position.

PMID- 22954989
TI  - Esthesioneuroblastoma with early drop metastasis to spinal cord.

PMID- 22954990
TI  - Primary isolated cerebellopontine angle papillary craniopharyngioma.

PMID- 22954991
TI  - Spontaneous intracranial hypotension: Detection of presumed site of spinal leak
      using T2 FIESTA MR imaging.

PMID- 22954992
TI  - Occipital lobe epidermoid cyst.

PMID- 22954993
TI  - Glossopharyngeal neuralgia due to ectatic anterior inferior cerebellar artery.

PMID- 22954994
TI  - Intracranial lipoma with subgaleal extension: An interesting case report with
      review of literature.

PMID- 22954995
TI  - Acute urine retention caused by lumbosacral sedimentation of subarachnoid
      hemorrhage in a patient with a ruptured internal carotid artery aneurysm.

PMID- 22954996
TI  - Compound elevated skull fracture mimicking a frontotemporoorbitozygomatic
      craniotomy flap.

PMID- 22954997
TI  - Endovascular treatment of ruptured wide-necked basilar tip aneurysm with Y
      stenting and coiling in a case of bilateral internal carotid artery occlusion
      with moyamoya disease.

PMID- 22954998
TI  - Free fat droplets from ruptured spinal tumors.

PMID- 22954999
TI  - A case of hemorrhagic Wernicke's encephalopathy following gastric surgery.

PMID- 22955000
TI  - The endoscopic trans-fourth ventricle aqueductoplasty and stent placement for the
      treatment of trapped fourth ventricle; stent blockage complications under
      estimated?

PMID- 22955001
TI  - Anti-inflammatory constituents from Tabebuia avellanedae.
AB  - Five novel compounds were isolated from the water extract of Tabebuia
      avellanedae, and their structures were established by analysis of NMR
      spectroscopy and mass spectrometry. Compounds 1-5 at 25MUM showed strong
      inhibitory activity on the inflammatory cytokine, tumor-necrosis factor-alpha and
      interleukin-1beta production in cultured human myeloma THP-1 cells co-stimulated
      with lipopolysaccharide without any significant cytotoxicity, and their anti
      allergic and antioxidant activities were evaluated.

PMID- 22955002
TI  - Haemolytic uraemic syndrome associated with bloody diarrhoea caused by
      Streptococcus dysgalactiae.

PMID- 22955003
TI  - [Antibiotic use in the community--the prevalence as a starting point].

PMID- 22955004
TI  - A 7-year randomized prospective study of a one-step self-etching adhesive in non
      carious cervical lesions. The effect of curing modes and restorative material.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical retention of a one
      step self-etching adhesive system (Xeno III) in Class V non-carious cervical
      lesions and the effect of restorative material and curing techniques on longevity
      of the restorations. MATERIALS AND METHODS: A total of 139 Class V restorations
      were placed with the self-etching primer Xeno III and a resin composite (Tetric
      Ceram) or a poly-acid modified resin composite (Dyract AP) in non-carious
      cervical lesions without intentional enamel involvement. The materials were cured
      with a conventional continuous light, a soft-start or a pulse-delay curing mode.
      The restorations were evaluated at baseline, 6, 12, 18 and 24 months and then
      yearly during a 7 year follow-up with modified USPHS criteria. Dentine bonding
      efficiency was determined by the percentage of lost restorations. RESULTS: During
      the 7 years, 135 restorations could be evaluated. No post-operative sensitivity
      was reported by the participants. Overall relative cumulative loss rate
      frequencies for the adhesive system at 6 and 18 months and 7 years, independent
      of curing technique and restorative material, were 0.8%, 6.9% and 23.0%,
      respectively. The self-etching adhesive fulfilled at 18 months the full
      acceptance ADA criteria. Tetric Ceram showed at 7 years a 20.9% loss of retention
      and Dyract AP a 25.0% loss rate (Log rank p = 0.48). The loss rates for the 3
      curing techniques: continuous, soft start and pulse delay were 17%, 27.9% and
      24.4%, respectively (Log rank p = 0.52). No secondary caries was observed.
      SIGNIFICANCE: The single-step self-etching adhesive showed acceptable clinical
      long-time retention rates to dentine surfaces independent of restorative material
      and curing technique used.

PMID- 22955005
TI  - Light transmission characteristics of dentine and resin composites with different
      thickness.
AB  - OBJECTIVE: The purpose of this study was to evaluate the light transmission
      characteristics of dentine and resin composites with different thickness.
      METHODS: Disks of bovine dentine and three resin composites (Estelite Sigma,
      Beautifil II and Clearfil Majesty) of OA2 shade were prepared with various
      thicknesses (0.5, 1.0 and 2.0mm). Using a goniophotometer, the distribution
      graphs of the light transmission intensity of each specimen were obtained, and
      diffusion factor (DF) as an indicator for a diffuse transmission property and
      peak-gain (G0) for a straight-line transmission property were calculated. Their
      colors were measured on black and white backings using a reflection
      spectrophotometer to calculate translucency parameter (TP). The data of each
      value (G0, DF and TP) were analyzed by two-way ANOVA and Dunnett's T3 for post
      hoc test (p=0.05). Regression analyses were used to determine the correlation
      between G0, DF, TP values and the thickness. RESULTS: Regardless of the
      thickness, dentine had lower TP values than the resin composites. 0.5 mm-thick
      specimens of dentine and resin composite produced various G0 and DF values, with
      dentine exhibiting significantly lower G0 and higher DF than the resin composites
      (p<0.05), whereas with the 1.0 and 2.0mm-thick specimens, they were closely
      aligned. For dentine, G0 and DF increased in inverse proportion to the thickness
      (G0: R(2)=0.962, p<0.001; DF: R(2)=0.891, p<0.001). CONCLUSIONS: Dentine had
      different light transmission characteristics from resin composite, depending on
      the thickness. CLINICAL SIGNIFICANCE: Dentine has different light transmission
      characteristics (straight-line and diffusion) from resin composite, depending on
      thickness. Resin composite restoration might be different to accurately reproduce
      light transmission characteristics of dentine substrate.

PMID- 22955006
TI  - Ethnic variations in pathways into early intervention services for psychosis.
AB  - BACKGROUND: Ethnic variations have previously been identified in the duration of
      untreated psychosis (DUP) and pathways into psychiatric services. These have not
      been examined in the context of early intervention services, which may alter
      these trajectories. AIMS: To explore ethnic differences in the nature and
      duration of pathways into early intervention services. METHOD: In a naturalistic
      cohort study, data were collected for 1024 individuals with psychotic disorders
      accepted for case management by eight London early intervention services.
      RESULTS: Duration of untreated psychosis was prolonged in the White British group
      compared with most other ethnic groups. White British individuals were more
      likely to make contact with their general practitioner and less likely to be seen
      within emergency medical services. All Black patient groups were more likely than
      their White British counterparts to experience involvement of criminal justice
      agencies. CONCLUSIONS: Variations continue to exist in how and when individuals
      from different ethnic groups access early intervention services. These may
      account for disparities in DUP.

PMID- 22955007
TI  - Adherence to treatment guidelines in clinical practice: study of antipsychotic
      treatment prior to clozapine initiation.
AB  - BACKGROUND: Clozapine is the only antipsychotic drug licensed for treatment
      resistant schizophrenia but its use is often delayed. Since previous studies,
      national guidelines on the use of clozapine and other antipsychotics have been
      disseminated to clinicians. AIMS: To determine the theoretical delay to clozapine
      initiation and to quantify the prior use of antipsychotic polypharmacy and high
      dose antipsychotic treatment. METHOD: Clinico-demographic data were extracted
      from the treatment records of all patients commencing clozapine in our centre
      between 2006 and 2010. RESULTS: Complete records were available for 149 patients.
      The mean theoretical delay in initiating clozapine was 47.7 months (s.d. = 49.7).
      Before commencing clozapine, antipsychotic polypharmacy and high-dose treatment
      was evident in 36.2 and 34.2% of patients respectively. Theoretical delay was
      related to illness duration (beta = 0.7, P<0.001) but did not differ by gender or
      ethnicity. CONCLUSIONS: Substantial delays to clozapine initiation remain and
      antipsychotic polypharmacy and high doses are commonly used prior to clozapine,
      despite treatment guidelines.

PMID- 22955008
TI  - Prediction of longer-term outcome of treatment-resistant depression in tertiary
      care.
AB  - BACKGROUND: Systematic studies on the outcome of treatment-resistant depression
      are scarce. AIMS: To describe the longer-term outcome and predictors of outcome
      in treatment-resistant depression. METHOD: Out of 150 patients approached, 118
      participants with confirmed treatment-resistant depression (unipolar, n = 77;
      bipolar, n = 27; secondary, n = 14) treated in a specialist in-patient centre
      were followed-up for between 8 and 84 months (mean = 39, s.d. = 22). RESULTS: The
      majority of participants attained full remission (60.2%), most of whom (48.3% of
      total sample) showed sustained recovery (full remission for at least 6 months). A
      substantial minority had persistent subsyndromal depression (19.5%) or persistent
      depressive episode (20.3%). Diagnosis of bipolar treatment-resistant depression
      and poorer social support were associated with early relapse, whereas strong
      social support, higher educational status and milder level of treatment
      resistance measured with the Maudsley Staging Method were associated with
      achieving quicker remission. Exploratory analysis of treatment found positive
      associations between treatment with a monoamine oxidase inhibitor (MAOI) in
      unipolar treatment-resistant depression and attaining remission at discharge and
      at final follow-up, and duloxetine use predicted attainment of remission at final
      follow-up. CONCLUSIONS: Although many patients with treatment-resistant
      depression experience persistent symptomatology even after intensive, specialist
      treatment, most can achieve remission. The choice of treatment and presence of
      good social support may affect remission rates, whereas those with low social
      support and a bipolar diathesis should be considered at higher risk of early
      relapse. We suggest that future work to improve the long-term outcome in this
      disabling form of depression might focus on social interventions to improve
      support, and the role of neglected pharmacological interventions such as MAOIs.

PMID- 22955009
TI  - Mediastinal adipose tissue expresses a pathogenic profile of 11 beta
      hydroxysteroid dehydrogenase Type 1, glucocorticoid receptor, and CD68 in
      patients with coronary artery disease.
AB  - OBJECTIVE: Cardiac visceral fat is accepted to be a new marker for
      cardiometabolic risk due to its association with increased cardiovascular risk
      factors. This study aimed to compare the expression of 11 beta hydroxysteroid
      dehydrogenases (11beta-HSD)-1, glucocorticoid receptor (GCR), and CD68 in
      mediastinal and subcutaneous adipose tissues (MAT, and SAT, respectively) and to
      assess their possible relationships with the development of coronary artery
      disease (CAD). METHODS AND RESULTS: Expression of 11beta-HSD-1, GCR, and CD68
      mRNA levels were measured by quantitative real-time polymerase chain reaction in
      MAT and SAT tissues of 37 patients undergoing coronary artery bypass grafting due
      to CAD (CAD group) and 19 non-CAD patients (controls) undergoing heart valve
      surgery. 11beta-HSD-1 in MAT and SAT and GCR expression in MAT and SAT were found
      to be significantly increased in CAD group when compared with controls (P<.05,
      respectively). In CAD group, 11beta-HSD-1 mRNA levels were found to be
      significantly higher in MAT compared to SAT (P<.05). CD68 mRNA levels were
      significantly higher in MAT of CAD group compared to controls (P<.05).
      Immunohistochemical analyses demonstrated the presence of CD68+ cells and
      increased 11beta-HSD-1 expression in MAT of CAD group compared to SAT.
      CONCLUSION: The present study demonstrate that the mediastinal fat exhibits a
      pathogenic mRNA profile of 11beta-HSD-1, GCR, and CD68. The identification of
      11beta-HSD-1 expression within the mediastinal fat, along with increased GCR
      expressions and the presence of CD68+ cells highlight that MAT potentially
      contributes to the pathogenesis of CAD.

PMID- 22955010
TI  - The effect of delay time between primary melanoma biopsy and sentinel lymph node
      dissection on sentinel node status, recurrence, and survival.
AB  - For primary melanoma, there is a delay between the initial skin biopsy and
      sentinel lymph node dissection, which may cause anxiety for the patient. The
      consequences of this delay on disease progression are unknown. The goal of this
      study was to determine whether delay time for sentinel node dissection from the
      initial cutaneous melanoma biopsy affects patient outcomes. A retrospective
      analysis of 492 patients with melanoma who underwent a sentinel node dissection
      between 1993 and 1999 was carried out. The endpoints assessed were sentinel node
      tumor status, recurrence, and mortality. Time to sentinel node dissection was
      compared between patients with positive and negative sentinel nodes. Long-term
      survival and recurrence were evaluated in relation to the time between the
      cutaneous biopsy and the sentinel node dissection (delay time), comparing less
      than 40 days with at least 40 days. In total, 15.9% of patients had positive
      sentinel nodes. The median follow-up was 11.7 years. Positive sentinel node
      patients had a median delay of 35 days between the primary melanoma biopsy and
      the sentinel node dissection compared with 41 days for negative sentinel node
      patients (P=0.5). Kaplan-Meier survival curves showed that a delay time of less
      than 40 days versus at least 40 days was not related to recurrence of melanoma
      (log-rank P=0.13) or overall survival (log-rank P=0.14). On multivariate analysis
      of age, thickness, ulceration, and sentinel node status, there was no difference
      in disease-free survival (P=0.58) or overall survival (P=0.53) between the less
      than 40 days and the at least 40 days groups. A modest delay in sentinel node
      dissection from the initial melanoma biopsy does not adversely affect sentinel
      node status, recurrence, nor survival.

PMID- 22955011
TI  - Incidence of cutaneous melanoma in Western Sweden, 1970-2007.
AB  - The aim of this study was to describe the increasing incidence of cutaneous
      malignant melanoma (CMM) in Western Sweden during the period 1970-2007. A
      secondary aim was to show a geographical variation in incidence between coastal
      and inland areas, considering the effects of the local average duration of
      sunshine, and the sun exposure-related behavior in the populations. The Swedish
      Cancer Registry provided data on invasive melanomas during 1970-2007.
      Meteorological maps showed the annual average duration of sunshine during 1961
      1990. A survey from 2007 with 2871 participants, carried out by the National
      Board of Health and Welfare, provided data on self-reported sun exposure. During
      the period studied, the age-standardized incidence for men in Western Sweden more
      than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to
      27.1/100 000. Coastal areas, including Gothenburg city, had a high average
      duration of sunshine (1701-1900 h of sun/year), whereas inland areas had lower
      average duration of sunshine (<=1700 h). The incidence of CMM was higher in
      coastal areas and in Gothenburg city, compared with inland areas. This may be
      linked to ultraviolet radiation, a consequence of the higher average duration of
      sunshine. The sun exposure survey showed additional factors, which possibly led
      to the increased incidence, for example high sun exposure on holidays abroad. The
      alarming increase in the incidence of CMM in Western Sweden, during the period
      1970-2007, shows the need for additional primary preventive measures, for example
      sun protection programs targeted at populations in this area.

PMID- 22955012
TI  - A digital wireless system for closed-loop inhibition of nociceptive signals.
AB  - Neurostimulation of the spinal cord or brain has been used to inhibit nociceptive
      signals in pain management applications. Nevertheless, most of the current
      neurostimulation models are based on open-loop system designs. There is a lack of
      closed-loop systems for neurostimulation in research with small freely-moving
      animals and in future clinical applications. Based on our previously developed
      analog wireless system for closed-loop neurostimulation, a digital wireless
      system with real-time feedback between recorder and stimulator modules has been
      developed to achieve multi-channel communication. The wireless system includes a
      wearable recording module, a wearable stimulation module and a transceiver
      connected to a computer for real-time and off-line data processing, display and
      storage. To validate our system, wide dynamic range neurons in the spinal cord
      dorsal horn have been recorded from anesthetized rats in response to graded
      mechanical stimuli (brush, pressure and pinch) applied in the hind paw. The
      identified nociceptive signals were used to automatically trigger electrical
      stimulation at the periaqueductal gray in real time to inhibit their own
      activities by the closed-loop design. Our digital wireless closed-loop system has
      provided a simplified and efficient method for further study of pain processing
      in freely-moving animals and potential clinical application in patients.

PMID- 22955013
TI  - Berberine inhibits mouse insulin gene promoter through activation of AMP
      activated protein kinase and may exert beneficial effect on pancreatic beta-cell.
AB  - Berberine is one of the main alkaloids of Rhizoma coptidis, proven to have anti
      diabetic potentials through activation of AMP activated protein kinase (AMPK) in
      liver and muscle. However, the role of berberine on the insulin gene is unknown.
      Therefore, the effect of berberine on insulin gene transcription was investigated
      in the present study. Reporter gene assays were used in the mouse beta-cell line
      NIT-1 to test the effect of berberine on the promoter of mouse insulin gene Ins2.
      The mRNA and protein levels of insulin were also detected. Diet induced glucose
      intolerant mice were used to explore the effect of berberine on blood glucose
      homeostasis and insulin resistance in vivo. The insulin content in islet was semi
      quantified by an image analysis software in the immunohistochemistry sections.
      The results revealed that berberine caused a reversible concentration-dependent
      inhibition of insulin gene transcription in NIT-1 cells which showed a
      significant difference from the long term used AMPK activator metformin. Such
      inhibition on insulin promoter resulted in the reduction of mRNA and protein of
      insulin. Furthermore, the inhibition of insulin promoter was totally abolished by
      AMPK inhibitor Compound C. Berberine significantly improved insulin resistance
      and glucose intolerance of mice. Likewise, insulin content in islets of berberine
      treated mice was also decreased. Thus, the insulin gene represents a novel target
      of AMPK that may contribute to the action of berberine in type 2 diabetes
      mellitus.

PMID- 22955014
TI  - Nitric oxide, can it be only good? Increasing the antioxidant properties of
      nitric oxide in hepatocytes by YC-1 compound.
AB  - The aim of the study was to evaluate the effect of Nitric oxide (NO) on redox
      changes and fat accumulation in hepatocytes. AML-12 hepatocytes were exposed to
      the NO donor Diethylenetriamine-NONOate (DETA-NO). DETA-NO led to a dose- and
      time-dependent increase in lipid accumulation in the cells, measured by Nile red
      fluorescence. Exposure of the cells to 1mM DETA-NO for 24h increased reactive
      oxygen species production, mainly peroxides. At the same time, NO induced
      elevation of reduced glutathione (GSH) and a mild activation of the antioxidant
      transcription factors Hypoxia-inducible factor 1alpha (HIF1alpha) and NF-E2
      related factor 2 (Nrf-2). We used 100 MUM YC-1 to inhibit HIF1alpha activity and
      induce activation of soluble Guanylate Cyclase (sGC). YC-1 alone did not affect
      fat accumulation, and only moderately increased the expression of Nrf-2-targeted
      genes Heme oxygenase 1 (Hmox1), NAD(P)H dehydrogenase (quinone 1) (Nqo1) and
      Glutathione S-transferase alpha1 (Gstalpha1). However, YC-1 abolished the
      negative effect of NO on fat accumulation when administered together. Strikingly,
      YC-1 potentiated the effect of NO on Nrf-2 activation, thus increasing
      dramatically the antioxidant properties of NO. Moreover, YC-1 intensified the
      effect of NO on the expression of peroxisome-proliferator-activated receptor
      gamma co-activator 1alpha (PGC1alpha) and mitochondrial biogenesis markers. This
      study suggests that YC-1 may shift the deleterious effects of NO into the
      beneficial ones, and may improve the antioxidant properties of NO.

PMID- 22955015
TI  - Structure-function relationship between the octopus perimeter cluster mean
      sensitivity and sector retinal nerve fiber layer thickness measured with the
      RTVue optical coherence tomography and scanning laser polarimetry.
AB  - PURPOSE: To determine structure-function relationship between each of 16 Octopus
      perimeter G2 program clusters and the corresponding 16 peripapillary sector
      retinal nerve fiber layer thickness (RNFLT) values measured with the RTVue-100
      Fourier-domain optical coherence tomography (RTVue OCT) and scanning laser
      polarimetry with variable corneal compensation (GDx-VCC) and enhanced corneal
      compensation (GDx-ECC) corneal compensation. METHODS: One eye of 110 white
      patients (15 healthy, 20 ocular hypertensive, and 75 glaucoma eyes) were
      investigated. The Akaike information criterion and the F test were used to
      identify the best fitting model. RESULTS: Parabolic relationship with logarithmic
      cluster mean sensitivity and linear sector RNFLT values provided the best fit.
      For RTVue OCT, significant (P<0.0001) coefficients of determination (R) were
      found for all 16 RNFLT sectors. The R values were highest for the temporal,
      superotemporal, and inferotemporal RNFLT sectors (0.4483 to 0.5186). For GDx
      VCC/ECC, significant (P<0.01) parabolic relationship was seen for all but the
      temporal and nasal RNFLT sectors. The overall highest R value (0.6943) was found
      for a superotemporal RNFLT sector with GDx-ECC. For some RNFLT sectors, the
      goodness of fit differed significantly between the imaging methods. Structure
      function relationship was similar for the total population and the glaucoma
      subgroup, whereas no relationship (P>0.05) was found for the control eyes.
      CONCLUSIONS: Mean sensitivity of the Octopus visual field clusters showed
      significant parabolic relationship with the corresponding peripapillary RNFLT
      sectors. The relationship was more general with the RTVue OCT than GDx-VCC or GDx
      ECC. The results show that visual field clusters of the Octopus G program can be
      applied for detailed structure-function research.

PMID- 22955016
TI  - Outcomes of shunt tube coverage with glycerol preserved cornea versus
      pericardium.
AB  - Pericardium is a biomaterial widely used for covering the outflow tubes of
      glaucoma drainage devices. Recently, glycerol preserved cornea has been
      introduced as an alternative that offers durability and improved cosmesis because
      of its clarity. We retrospectively reviewed 262 patients in the University of
      Alabama Birmingham Glaucoma Service who underwent shunt procedures using either
      cornea tissue or pericardium to cover the tube. The primary outcome measure was
      the number of erosions of the covering material. Nine out of 101 (8.9%) patients
      in the pericardium covered group experienced an erosion compared with 3 out of
      161 (1.9%) in the cornea covered group. A significant difference was reached with
      P=0.0125. Median follow-up was 440 days for the cornea group and 331 days for the
      pericardium group. The type of glaucoma (primary open-angle glaucoma vs.
      secondary glaucoma) was not associated with the risk of erosion (odds ratio,
      0.501; 95% confidence interval, 0.204-1.234). The median time to exposure was 252
      days in the pericardium group and 440 days in the cornea group (P=0.0017). 

PMID- 22955017
TI  - Accumulation of MS2, GA, and Qbeta phages on high density polyethylene (HDPE) and
      drinking water biofilms under flow/non-flow conditions.
AB  - Accumulation of enteric viruses on surfaces within a drinking water distribution
      system was investigated in a reactor using three F-specific RNA bacteriophages
      (MS2, GA, and Qbeta) as models of human pathogenic viruses. The influence of
      hydrodynamic versus hydrostatic conditions and the effect of the colonization of
      HDPE surfaces with two-month-old biofilms were assessed for virus accumulation on
      surfaces. In order to work under controlled laminar conditions and to study
      various wall shear stresses at the same time, a new rotating disc reactor was
      designed. Among the wall shear rates applied in the reactor (450 to 1640 s(-1))
      no significant differences were observed concerning both the total number of
      bacteria, which was found to be around 1.7 * 10(7) cells/cm(2) and the virus
      concentrations on surfaces were about 3 * 10(4), 5 * 10(5) and 3 * 10(5) eq
      PFU/cm(2) for MS2, GA and Qbeta phages, respectively. Comparison between static
      versus dynamic conditions revealed that both Brownian diffusion and convective
      diffusion were involved in the transport of these soft colloidal particles and an
      increase reaching about 1 log in virus concentrations measured on surfaces
      appeared when hydrodynamic conditions where applied. Our results also showed the
      influence of the colonization by two-month-old drinking water biofilms which led
      to a change in the level of virus adhesion. The implication of the physico
      chemical properties was also underlined since different adhesion profiles were
      obtained for the three bacteriophages and MS2 phage was found to be the less
      adherent one whatever the conditions applied.

PMID- 22955018
TI  - Racial differences between blacks and whites with systemic sclerosis.
AB  - PURPOSE OF REVIEW: Racial disparities appear to exist in the susceptibility and
      severity of systemic sclerosis (SSc, scleroderma) and are responsible for a
      greater health burden in blacks as compared with whites. Disparities in
      socioeconomic status and access to healthcare do not sufficiently explain the
      observed differences in prevalence and mortality. It is important to determine
      whether there might be a biologic basis for the racial disparities observed in
      SSc. RECENT FINDINGS: We present data to suggest that the increased
      susceptibility and severity of SSc in blacks may result in part from an imbalance
      of profibrotic and antifibrotic factors. Racial differences in the expression of
      transforming growth factor-beta1 (TGF-beta1) and caveolin-1, as well as
      differences in the expression of hepatocyte growth factor and PPAR-gamma, have
      been demonstrated in blacks with SSc, as well as in normal black individuals. A
      genetic predisposition to fibrosis may account for much of the racial disparities
      between black and white patients with SSc. SUMMARY: A better understanding of the
      biologic basis for the racial disparities observed in SSc may lead to improved
      therapies, along with the recognition that different therapies may need to be
      adapted for different groups of patients.

PMID- 22955019
TI  - Renal disease in scleroderma:  an update on evaluation, risk stratification,
      pathogenesis and management.
AB  - PURPOSE OF REVIEW: Renal disease remains an important cause of morbidity and
      mortality in scleroderma. The spectrum of renal complications in systemic
      sclerosis includes scleroderma renal crisis (SRC), normotensive renal crisis,
      antineutrophil cytoplasmic antibodies-associated glomerulonephritis,
      penacillamine-associated renal disease, and reduced renal functional reserves
      manifested by proteinuria, microalbuminuria, or isolated reduction in glomerular
      filtration rate. The purpose of this review is to provide a concise and up-to
      date review of the evaluation, risk stratification, pathogenesis, and management
      of scleroderma-associated renal disease. RECENT FINDINGS: Although SRC survival
      has significantly improved, mortality of this complication remains high outside
      of specialized centers. Recent data demonstrate strong associations between anti
      RNA polymerase III antibodies and SRC. Subclinical renal impairment affects
      approximately 50% of scleroderma patients and may be associated with other
      vascular manifestations. Subclinical renal involvement rarely progresses to end
      stage renal failure; however, recent studies suggest it may predict mortality in
      patients with other vasculopathic manifestations. SUMMARY: Testing for anti-RNA
      polymerase III antibodies should be incorporated into clinical care to identify
      patients at high risk for SRC. Recommendations from European League Against
      Rheumatism (EULAR), EULAR Scleroderma Trials and Research, and the Scleroderma
      Clinical Trials Consortium confirm angiotensin-converting enzyme inhibitors as
      first-line therapy for SRC, and give recommendations for second-line agents.

PMID- 22955020
TI  - Interstitial lung disease:  is interstitial lung disease the same as scleroderma
      lung disease?
AB  - PURPOSE OF REVIEW: Pulmonary fibrosis is a devastating disease that affects
      millions of people worldwide. Among the most common forms of lung fibrosis are
      idiopathic pulmonary fibrosis (IPF) and scleroderma-related interstitial lung
      disease (SSc-ILD). Despite a wealth of literature regarding each of these
      diseases, studies that directly compare IPF and SSc-ILD are rare. RECENT
      FINDINGS: This review compares the salient features of IPF and SSc-ILD. Clinical
      presentation and demographics will be presented, along with the newly released
      radiographic and pathologic criteria for IPF. Evolving concepts of pathogenesis
      including the role of structural cell injury, the pathogenic role of macrophages
      and lymphocytes, and the origin of fibroblasts are described. We conclude with
      new developments in the search for predictive biomarkers of disease progression,
      such as markers of epithelial injury, lymphocyte subsets, and circulating
      fibrocytes, will be presented. We conclude with a discussion of the results of
      recent clinical trials. SUMMARY: It is found that despite differences in clinical
      presentation and response to treatment, similarities are noted in proposed
      pathogenesis and putative biomarkers. It is hoped that this information will lead
      to studies aimed at understanding the factors driving these difficult to treat
      and often deadly diseases.

PMID- 22955021
TI  - Therapeutic advances in myositis.
AB  - PURPOSE OF REVIEW: To review the treatment advances of the inflammatory
      myopathies, a heterogeneous group of diseases that includes polymyositis,
      dermatomyositis, and inclusion body myositis. RECENT FINDINGS: There are few
      clinical trials in myositis, making it difficult to provide clear recommendations
      on the treatment of these rare disorders. The current management for IIM includes
      the initial use of corticosteroids followed by various conventional second-line
      treatments such as methotrexate and azathioprine. Although these drugs have not
      been tested in rigorous randomized controlled trials, general expert consensus
      confirms their use. Intravenous immunoglobulin is a reasonable short-term
      treatment with proven benefit in one controlled trial, although the evidence for
      other immunosuppressive therapies has been derived mainly from uncontrolled
      studies. Cyclosporine or tacrolimus have shown efficacy in myositis including
      those patients with interstitial lung disease (ILD), whereas mycophenolate
      mofetil is effective in both polymyositis and refractory dermatomyosits
      (including recalcitrant rash) and ILD. Uncontrolled studies for rituximab are
      encouraging but results from the largest randomized controlled trial in myositis
      failed to meet the primary endpoint. Anti-tumor necrosis factor (TNF) agents have
      shown mixed results in small, randomized clinical trials with infliximab
      demonstrating no benefit and etanercept leading to encouraging results warranting
      further study. Some newer novel therapies such as ACTH analogues and tocilizumab
      require additional investigation. SUMMARY: The balance of evidence suggests that
      traditional immunosuppressive and immunomodulatory drugs are certainly effective
      in polymyositis and dermatomyositis despite the lack of randomized controlled
      trials. Newer therapies are being studied but no major breakthroughs have been
      realized.

PMID- 22955022
TI  - Myositis autoantibodies.
AB  - PURPOSE OF REVIEW: To review recent advances in our understanding of
      autoantibodies associated with dermatomyositis and the autoimmune necrotizing
      myopathies. RECENT FINDINGS: Autoantibodies preferentially associated with
      dermatomyositis include those recognizing Mi-2, MDA5, TIF1gamma, and NXP-2. Each
      of these is associated with a distinct clinical phenotype. Autoantibodies found
      in patients with autoimmune necrotizing myopathies recognize signal recognition
      particle and 3-hydroxy-3-methylglutaryl-coenzime A reductase (HMG-CoA) reductase.
      The latter are found in patients with statin-associated autoimmune muscle
      disease. SUMMARY: As these are helpful both diagnostically and prognostically, a
      rheumatologist should be familiar with autoantibodies found in patients with
      dermatomyositis and the autoimmune necrotizing myopathies.

PMID- 22955024
TI  - Comparing and contrasting muscle disease across the continuum highlights shared
      pathways and presentations of muscle dysfunction.

PMID- 22955023
TI  - Sarcopenia in older adults.
AB  - PURPOSE OF REVIEW: Sarcopenia, or the decline of skeletal muscle tissue with age,
      is one of the most important causes of functional decline and loss of
      independence in older adults. The purpose of this article is to review the
      current definitions of sarcopenia, its potential causes and clinical
      consequences, and the potential for intervention. RECENT FINDINGS: Although no
      consensus diagnosis has been reached, sarcopenia is increasingly defined by both
      loss of muscle mass and loss of muscle function or strength. Its cause is widely
      regarded as multifactorial, with neurological decline, hormonal changes,
      inflammatory pathway activation, declines in activity, chronic illness, fatty
      infiltration, and poor nutrition, all shown to be contributing factors. Recent
      molecular findings related to apoptosis, mitochondrial decline, and the
      angiotensin system in skeletal muscle have highlighted biological mechanisms that
      may be contributory. Interventions in general continue to target nutrition and
      exercise. SUMMARY: Efforts to develop a consensus definition are ongoing and will
      greatly facilitate the development and testing of novel interventions for
      sarcopenia. Although pharmaceutical agents targeting multiple biological pathways
      are being developed, adequate nutrition and targeted exercise remain the gold
      standard for therapy.

PMID- 22955025
TI  - Magnetic resonance elastography as a predictor of insufficient liver enhancement
      on gadoxetic acid-enhanced hepatocyte-phase magnetic resonance imaging in
      patients with type C hepatitis and Child-Pugh class A disease.
AB  - OBJECTIVES: The aim of this study was to examine liver stiffness value measured
      by magnetic resonance elastography (MRE) and laboratory test results to find the
      best method for predicting insufficient liver enhancement on gadoxetic acid
      enhanced hepatocyte-phase images. MATERIALS AND METHODS: The institutional ethics
      committee approved this retrospective study with waiver of informed consent. In
      total, 118 patients with Child-Pugh class A disease and type C hepatitis
      underwent MRE and gadoxetic acid-enhanced magnetic resonance imaging. During MRE
      examination, a pneumatic passive driver was used to obtain liver stiffness in
      kPa. Liver enhancement was assessed using liver-to-spleen contrast ratio (LSR),
      calculated using signal intensities of the liver and spleen on hepatocyte-phase
      magnetic resonance images obtained 20 minutes after contrast administration of
      gadoxetic acid. Insufficient liver enhancement was defined as an LSR lower than
      1.5. The following laboratory test results were used as possible predictors of
      insufficient liver enhancement as well as liver stiffness measured by MRE:
      albumin, total bilirubin, aspartate aminotransferase, percentage prothrombin
      time, and platelet count. Correlation coefficients were calculated between LSR
      and these variables. Logistic analysis was performed to determine independent
      predictors of insufficient liver enhancement. RESULTS: All possible predictors
      investigated were significantly correlated with LSR. Logistic regression analysis
      revealed that MRE was the only variable to predict insufficient liver
      enhancement, with an odds ratio (95% confidence interval) of 2.03 (1.22-3.85) (P
      = 0.0138). A cutoff value of greater than 6.4 kPa yielded 95% specificity for
      predicting insufficient liver enhancement. CONCLUSION: Gadoxetic acid is not
      recommended in patients with liver stiffness greater than 6.4 kPa (consistent
      with severe fibrosis) because of insufficient liver enhancement on hepatocyte
      phase images.

PMID- 22955026
TI  - Ultrasound-guided diagnosis and aspiration of Baker's cyst.

PMID- 22955027
TI  - How assistive technology use by individuals with disabilities impacts their
      caregivers: a systematic review of the research evidence.
AB  - Informal caregivers are a critical yet frequently unacknowledged part of the
      healthcare system. It is commonly presumed that providing assistive technology
      will decrease the burden of their care provision; however, no review has
      evaluated the evidence behind this assumption. Therefore, a systematic review was
      undertaken to evaluate evidence of the impact of assistive technology use by care
      recipients on their informal caregivers. Data sources included EMBASE, MEDLINE,
      Cumulative Index to Nursing and Allied Health Literature, Web of Science,
      PsychINFO, PubMed, and active researchers in this area. Twenty-two studies met
      the specified inclusion criteria. Collectively, the findings suggest that
      assistive technology use helps caregivers by diminishing some of the physical and
      emotional effort entailed in supporting individuals with disability. However,
      confidence in this causal connection is limited because of the study designs that
      were used. This undermines the understanding of the impacts of assistive
      technology use on the users' informal caregivers.

PMID- 22955028
TI  - Ramsay-Hunt syndrome accompanied by dysphagia: a videofluoroscopic swallowing
      study.

PMID- 22955029
TI  - State of intracortical inhibitory interneuron activity in patients with chronic
      stroke.
AB  - OBJECTIVES: Few studies have assessed short intracortical inhibition (SICI) in
      the affected hemisphere (AH) in a large number of patients with chronic stroke.
      In this study, SICI was assessed in chronic stroke patients with severe
      hemiparesis, and its relationship to clinical parameters was examined. METHODS:
      The participants were 72 patients with chronic hemiparetic stroke. SICI of both
      the AH and the unaffected hemisphere (UH) was assessed. The relationships between
      SICI and the location of lesion, time from onset, and finger function were
      studied. Motor function of the paretic finger was assessed with the Stroke
      Impairment Assessment Set (SIAS) and the Fugl-Meyer test upper extremity motor
      score. To compare the results with those of healthy subjects, SICI was assessed
      in seven age-matched control subjects. RESULTS: MEPs of the UH were evoked in all
      72 subjects, and MEPs of the AH were evoked in 24 subjects. SICI of the AH was
      inversely correlated with paretic finger motor function and time from stroke
      onset. SICI of the UH was not correlated with either one. SICI of the UH was
      higher in the cortical lesion group than in the control group. CONCLUSIONS: The
      state of intracortical inhibitory neuron activity depends on the state of motor
      function and lesion site even in chronic stroke patients with severe hemiparesis.
      SIGNIFICANCE: The inhibitory system of the AH is involved in functional recovery
      of the paretic hand even in the chronic stage of stroke.

PMID- 22955030
TI  - An investigation into the suitability of some etching reagents to restoring
      obliterated stamped numbers on cast iron engine blocks of cars.
AB  - Most of the automotive companies use cast iron for their engine blocks.
      Restoration of obliterated number on these iron surfaces by chemical etching is
      known to be quite difficult. Heating of the obliterated surface using
      oxyacetylene flame is an alternative recovery treatment suggested in literature
      and used in practice. However chemical etching has been established to be the
      most sensitive technique for detection of metal deformation present under stamped
      serial numbers. Hence, the current work investigated the suitability of some
      common etchants on cast iron surfaces with a view to determining the most
      suitable one for revealing the obliterated marks. The reagents tested were mostly
      copper containing Fry's reagent and its modifications. Two cast iron engine
      blocks (3.29%C and 3.1%C) of two cars--a Proton Saga and a Toyota--were utilized
      for the experiments. The engine blocks were cut into several small plates and
      each plate was stamped with some numerical characters at 8 kN load using Instron
      Table Mounted Universal Testing Machine. The depth of stamping impression varied
      between 0.2 mm and 0.3 mm. The stamped number was completely ground off manually
      using a metal file. The grounded surface was then polished smooth using emery
      papers and etched with a few selected reagents mostly by swabbing. Experimental
      results showed that a modified Fry's composition consisting of 4 5g CuCl(2), 100
      mL HCl, and 180 mL H(2)O restored the number with better contrast at a reasonably
      shorter time. The above reagent is a slightly modified form of one of the Fry's
      original compositions--45 g CuCl(2), 180 mL HCl, and 100 mL H(2)O. Quite
      importantly the proposed reagent restored the original stamped numbers of both
      Proton and Toyota cars and also a Mitsubishi car that had been obliterated. The
      most widely used Fry's composition (90 g CuCl(2), 120 mL HCl and 100 mL H(2)O),
      although recovered the obliterated number, did not cause the desired contrast.

PMID- 22955031
TI  - Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin
      A by synthetic peptides.
AB  - Staphylococcus aureus is a major human pathogen producing different types of
      toxins. Enterotoxin A (SEA) is the most common type among clinical and food
      related strains. The aim of the present study was to estimate functional regions
      of SEA that are responsible for emetic and superantigenic activities using
      synthetic peptides. A series of 13 synthetic peptides corresponding to specific
      regions of SEA were synthesized, and the effect of these peptides on
      superantigenic activity of SEA including interferon gamma (IFN-gamma) production
      in mouse spleen cells, SEA-induced lethal shock in mice, spleen cell
      proliferation in house musk shrew, and emetic activity in shrews were assessed.
      Pre-treatment of spleen cells with synthetic peptides corresponding to the
      regions 21-40, 35-50, 81-100, or 161-180 of SEA significantly inhibited SEA
      induced IFN-gamma production and cell proliferation. These peptides also
      inhibited SEA-induced lethal shock. Interestingly, peptides corresponding to
      regions 21-40, 35-50 and 81-100 significantly inhibited SEA-induced emesis in
      house musk shrews, but region 161-180 did not. These findings indicated that
      regions 21-50 and 81-100 of SEA are important for both superantigenic and emetic
      activities of SEA molecule while region 161-180 is involved in superantigenic
      activity but not emetic activity of SEA. These regions could be important targets
      for therapeutic intervention against SEA exposure.

PMID- 22955032
TI  - Purification and characterization of novel antioxidant peptides from enzymatic
      hydrolysates of tilapia (Oreochromis niloticus) skin gelatin.
AB  - To obtain hydrolysates with high degree of hydrolysis (DH) and scavenging radical
      activity, tilapia skin gelatin (TSG) was hydrolyzed by properase E and multifect
      neutral. The optimum hydrolysis condition of each enzyme was determined using the
      orthogonal experiment, and double-enzyme hydrolysis was further applied. The
      results showed the tilapia skin gelatin hydrolysate (TSGH) obtained by
      progressive hydrolysis using multifect neutral and properase E had the highest DH
      and hydroxyl radical scavenging activity. The IC(50) values of TSGH on scavenging
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (.O(2))
      and hydroxyl radical (.OH) activities were also determined. TSGH was further
      purified using gel filtration chromatography, ion exchange chromatography, and RP
      HPLC. The peptides were identified using nano-LC-ESI mass spectrometry. Finally,
      two antioxidant peptides were identified and the amino acid sequences were Glu
      Gly-Leu (317.33 Da) and Tyr-Gly-Asp-Glu-Tyr (645.21 Da), respectively. The IC(50)
      values of two peptides on hydroxyl radical scavenging activities were 4.61 MUg
      mL(-1)and 6.45 MUg mL(-1), respectively. Therefore, the results demonstrated that
      the hydrolysates of TSG prepared by multifect neutral and properase E could serve
      as a source of peptides with high antioxidant activity. It provided a scientific
      basis for the preparation of antioxidant peptides.

PMID- 22955033
TI  - Peptide sequences mediating tropism to intact blood-brain barrier: an in vivo
      biodistribution study using phage display.
AB  - Peptide motifs that demonstrate tropism for the blood brain barrier (BBB) are of
      real translational value in developing innovative delivery strategies for
      biological brain targeted therapies. In vivo peptide-phage display affords
      peptide selection against the full complement of biological markers within the
      correct cellular macro- and micro-environments. Here a stringent in vivo
      biopanning protocol was employed in the rat aimed at identifying cyclic 7-mer
      peptide motifs that mediate tropism to brain microvasculature. Five rounds of
      biopanning identified 349 unique peptide motifs in the brain tissue gray matter
      compartment (microvasculature and parenchyma). While in general no consensus was
      evident linking peptide physico-chemical properties and brain tropism, peptides
      bearing c-SxTSSTx-c or c-xxxSSTx-c motifs were found to be present in high
      abundance. Based on amino acid frequency distribution of the 349 unique peptides
      sequences a theoretical 'idealized' peptide pattern, c-PP(S/P)SSST-c, could be
      derived. For the most abundant experimental peptide sequence found in brain
      tissue, c-SYTSSTM-c, an in vivo pharmacokinetic and whole body tissue
      biodistribution study was performed. Based upon tissue exposure data (i.e. tissue
      AUC((0-infinity))) the sequence c-SYTSSTM-c efficiently retargeted phage virions
      to the brain providing an approximate 5-fold greater (P<0.05) accumulation in
      brain over control phage; in all other organs no significant (P>0.05) difference
      in tissue tropism between c-SYTSSTM-c and control phages were evident. This
      peptide and more generally the peptide motifs, -SxTSSTx- or -xxxSSTx-, warrant
      further investigation as agents mediating sequence-dependent tropism to brain
      microvasculature potentially able to deliver biologic cargo to the CNS.

PMID- 22955034
TI  - Molecular cloning and functional analysis of two FAD2 genes from American grape
      (Vitis labrusca L.).
AB  - The synthesis of polyunsaturated fatty acids (PUFAs), the most abundant fatty
      acids in plants, begins with a reaction catalyzed by fatty acid desaturase 2
      (FAD2; EC 1.3.1.35), also called microsomal oleate Delta12-desaturase. Since the
      FAD2 gene was first identified in Arabidopsis thaliana, FAD2 research has gained
      wide interest as the essential enzyme for synthesizing PUFA. Grapes are one of
      the most frequently cultivated fruits in the world, with most commercial growers
      cultivating Vitis vinifera and V. labrusca. Grapeseed oil contains a high
      proportion, 60-70% of linoleic acid (18:2). We cloned two putative FAD2 genes
      from V. labrusca cv. Campbell Early based on V. vinifera genome sequences.
      Deduced amino acid sequences of two putative genes showed that VlFAD2s show high
      similarity to Arabidopsis FAD2 and commonly contain six transmembrane domain,
      three histidine boxes and endoplasmic reticulum (ER) retrieval motif representing
      the characteristics of fatty acid desaturase. Phylogenetic analyses of various
      plant FAD2s showed that VlFAD2-1 and VlFAD2-2 are separately grouped with
      constitutive and seed-type FAD2s, respectively. Southern blot showed that one or
      two bands are found in each lane. Because Campbell Early is a hybrid cultivar,
      FAD2-1 and FAD2-2 genes may exist as one copy in V. labrusca. Expression analysis
      in different tissues indicated that VlFAD2-1 is a constitutive gene but VlFAD2-2
      is a seed-type gene. Complementation experiments of fad2-1 mutant Arabidopsis
      with VlFAD2-1 or VlFAD2-2 demonstrated that VlFAD2-1 and VlFAD2-2 can restore low
      PUFA proportion of fad2 to normal PUFA proportion.

PMID- 22955035
TI  - 28-Day safety and tolerability of umeclidinium in combination with vilanterol in
      COPD: a randomized placebo-controlled trial.
AB  - BACKGROUND: Umeclidinium (UMEC; GSK573719) is a new long-acting muscarinic
      antagonist (LAMA) currently in development in combination with vilanterol (VI),
      an inhaled, long-acting beta2 agonist for the treatment of chronic obstructive
      pulmonary disease (COPD). The primary aim of this study was to evaluate the
      safety and tolerability of repeat dosing of UMEC and VI in combination once daily
      for 28 days in patients with COPD. METHODS: This was a multicenter, double-blind,
      placebo-controlled, parallel group study. Patients aged >=40 years with post
      bronchodilator FEV1 <=80% of predicted normal values and FEV1/FVC ratio <=0.70,
      and a smoking history of >=10 pack-years, were randomized 4:1 to once-daily
      UMEC/VI (500/25 mcg; n = 42) or placebo (n = 9). RESULTS: UMEC/VI was non
      inferior to placebo in weighted mean pulse rate over 0-6 h at Day 28 (primary
      endpoint: difference of -0.5 bpm, 95% CI: -5.5 to 4.5). There was no evidence of
      a difference between UMEC/VI compared with placebo in blood pressure, minimum and
      maximum pulse rate, or QTcF assessments. Adverse events (AEs) were reported by 11
      (26%) patients in the UMEC/VI group and one (11%) patient in the placebo group.
      No serious AEs were reported. Both UMEC and VI showed rapid absorption (median
      t(max) ~6 min for both drugs) with no evidence of accumulation for AUC or C(max)
      on Day 28 compared with Day 1 for UMEC or VI. There was no correlation between
      individual steady-state C(max) and pulse rate on Day 28. Change from baseline in
      trough FEV1 on Day 29 showed numerically greater improvements with UMEC/VI
      compared with placebo. CONCLUSION: Once-daily dosing with UMEC in combination
      with VI in patients with moderate-to-very-severe COPD was well tolerated over 28
      days.

PMID- 22955036
TI  - Streptococcus pneumoniae meningitis following postoperative endophthalmitis.

PMID- 22955037
TI  - Corneal birefringence measurements in normal Indian eyes.

PMID- 22955038
TI  - Blue-blocking intraocular implants should be used routinely during
      phacoemulsification surgery--no.

PMID- 22955039
TI  - Blue-blocking intraocular implants should be used routinely during
      phacoemulsification surgery--yes.

PMID- 22955040
TI  - [Response to: User satisfaction with hospital emergency services].

PMID- 22955041
TI  - WITHDRAWN:beta-Catenin Plays a Key Role in Lumbar Intervertebral Disc
      Degeneration.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 22955042
TI  - The effects of Salsa dance on balance, gait, and fall risk in a sedentary patient
      with Alzheimer's dementia, multiple comorbidities, and recurrent falls.
AB  - BACKGROUND AND PURPOSE: Recent studies have looked at the effects of dance on
      functional outcomes for persons with balance, gait, and cognitive impairments.
      The purpose of this report is to quantify the effects of Salsa dance therapy on
      function, balance, and fall risk in a sedentary older patient with multiple
      comorbidities. CASE DESCRIPTION/INTERVENTION: The patient was an 84-year-old
      woman with functional decline due to Alzheimer's dementia, late effects of a
      cerebral hemorrhagic aneurysm with right hemiparesis in the lower extremity,
      arthritis, and recurrent falls. Intervention consisted largely of Salsa dancing
      activities for 24 sessions over 12 weeks. OUTCOMES: The patient showed
      improvements in range of motion, strength, balance, functional mobility, gait
      distance, and speed. During the course of therapy, 1 fall was reported with no
      significant injuries and 6 months postintervention the patient/caregiver reported
      no falls. DISCUSSION: This case describes the clinically meaningful effects of
      Salsa dance therapy as a primary intervention and its impact on functional
      recovery in a geriatric patient with multiple impairments.

PMID- 22955044
TI  - Prospective study of optimal obesity index cutoffs for predicting development of
      multiple metabolic risk factors: the Korean genome and epidemiology study.
AB  - BACKGROUND: In this prospective cohort study, we estimated the risk of developing
      more than 1 metabolic risk factor, using different obesity indices. In addition,
      we investigated the relative usefulness of the obesity indices for predicting
      development of such risk factors and calculated optimal cutoffs for the obesity
      indices. METHODS: The cohort comprised 10 038 representative residents of a small
      city and a rural county who were recruited in 2001-2002. Follow-up examinations
      were conducted every 2 years. Among the 3857 participants without metabolic
      syndrome at baseline, 1102 new cases occurred during the 6-year follow-up.
      Receiver operating characteristic (ROC) curves for the obesity indices were
      plotted to compare the usefulness of the obesity indices. RESULTS: The numbers of
      new cases of multiple metabolic risk factors among people in the highest
      quintiles of body mass index (BMI), waist circumference (WC), waist-hip ratio
      (WHR), and waist-height ratio at the baseline examination were 2 to 3 times those
      in the lowest quintiles. The area under the ROC curve for WHR was significantly
      higher than that for BMI. The optimal BMI cutoff was 24 kg/m(2) in men and women,
      and the optimal WC cutoffs were 80 cm and 78 cm in men and women, respectively.
      CONCLUSIONS: Both overall obesity and central obesity predicted risk of
      developing multiple metabolic risk factors, and WHR appeared to be a better
      discriminator than BMI. To prevent development of metabolic diseases among
      Koreans, it might be useful to lower the cutoff for abdominal obesity, as defined
      by WC.

PMID- 22955043
TI  - Study protocol for the Fukushima Health Management Survey.
AB  - BACKGROUND: The accidents that occurred at the Fukushima Daiichi Nuclear Power
      Plant after the Great East Japan Earthquake on 11 March 2011 have resulted in
      long-term, ongoing anxiety among the residents of Fukushima, Japan. Soon after
      the disaster, Fukushima Prefecture launched the Fukushima Health Management
      Survey to investigate long-term low-dose radiation exposure caused by the
      accident. Fukushima Medical University took the lead in planning and implementing
      this survey. The primary purposes of this survey are to monitor the long-term
      health of residents, promote their future well-being, and confirm whether long
      term low-dose radiation exposure has health effects. This report describes the
      rationale and implementation of the Fukushima Health Management Survey. METHODS:
      This cohort study enrolled all people living in Fukushima Prefecture after the
      earthquake and comprises a basic survey and 4 detailed surveys. The basic survey
      is to estimate levels of external radiation exposure among all 2.05 million
      residents. It should be noted that internal radiation levels were estimated by
      Fukushima Prefecture using whole-body counters. The detailed surveys comprise a
      thyroid ultrasound examination for all Fukushima children aged 18 years or
      younger, a comprehensive health check for all residents from the evacuation
      zones, an assessment of mental health and lifestyles of all residents from the
      evacuation zones, and recording of all pregnancies and births among all women in
      the prefecture who were pregnant on 11 March. All data have been entered into a
      database and will be used to support the residents and analyze the health effects
      of radiation. CONCLUSIONS: The low response rate (<30%) to the basic survey
      complicates the estimation of health effects. There have been no cases of
      malignancy to date among 38 114 children who received thyroid ultrasound
      examinations. The importance of mental health care was revealed by the mental
      health and lifestyle survey and the pregnancy and birth survey. This long-term
      large-scale epidemiologic study is expected to provide valuable data in the
      investigation of the health effects of low-dose radiation and disaster-related
      stress.

PMID- 22955045
TI  - Low LET protons focused to submicrometer shows enhanced radiobiological
      effectiveness.
AB  - This study shows that enhanced radiobiological effectiveness (RBE) values can be
      generated focusing low linear energy transfer (LET) radiation and thus changing
      the microdose distribution. 20 MeV protons (LET = 2.65 keV um(-1)) are focused to
      submicrometer diameter at the ion microprobe superconducting nanoprobe for
      applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The
      RBE values, as determined by measuring micronuclei (RBE(MN) = 1.48 +/- 0.07) and
      dicentrics (RBE(D) = 1.92 +/- 0.15), in human-hamster hybrid (A(L)) cells are
      significantly higher when 117 protons were focused to a submicrometer irradiation
      field within a 5.4 * 5.4 um(2) matrix compared to quasi homogeneous in a 1 * 1
      um(2) matrix applied protons (RBE(MN) = 1.28 +/- 0.07; RBE(D) = 1.41 +/- 0.14) at
      the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV
      (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied
      per point deposit the same amount of energy like a (12)C ion with 55 MeV total
      energy (4.48 MeV u(-1)). The enhancements are about half of that obtained for
      (12)C ions (RBE(MN) = 2.20 +/- 0.06 and RBE(D) = 3.21 +/- 0.10) and they are
      attributed to intertrack interactions of the induced damages. The measured RBE
      values show differences from predictions of the local effect model (LEM III) that
      is used to calculate RBE values for irradiation plans to treat tumors with high
      LET particles.

PMID- 22955046
TI  - Oxidative stress induced by arsenopyrite and the role of desferrioxamine-B as
      radical scavenger.
AB  - Arsenopyrite (FeAsS) is one of the earth's primary mineral sources of As, yet its
      effects on cell damage remain largely unknown. This paper addresses the question
      whether FeAsS induces lipid peroxidation (LP), a major indicator of oxidative
      stress. Screening and monitoring of LP was conducted using Thiobarbituric Acid
      Reactive Substances (TBARSs) assay. The lipid source was supernatant of rat brain
      homogenates. The formation of TBARS by FeAsS was rapid and took place just after
      10 min. Maximum TBARS levels (ca. 14 nmol TBARS per mg of protein) were observed
      after 1h and remained constant thereafter. Suspension fraction separations showed
      that dissolved and structural components contributed to LP. The formation of
      TBARS by soluble As, As(III) or As(V), compared to basal levels. The initiation
      of LP by FeAsS was consistent with a mechanism initiated by the Fe(3+)/O(2)(-)
      redox system, and differed initiated by Fe(2+)/O(2). The effectiveness of FeAsS
      and FeSO(4) as inducer compared, and surpassed that of AAPH. On the other hand,
      the initiation of LP by FeAsS is consistent with a mechanism initiated by
      perferryl ion and Fe(3+)/O(2)(-), and differs from the mechanism characteristic
      of FeSO(4) initiated by the Fe(2+)/O(2) redox system. Proposedly, FeAsS surfaces
      contain a mixture of Fe(3+) and Fe(2+) that, along with O(2) and O(2)(-),
      participate in multiple mechanisms of electron transfer. EPR determinations show
      decreases in DMPO-OH adduct signal in FeAsS suspensions after adding
      desferrioxamine-B (DFO-B), consistent with the idea that DFO-B serves as a
      radical scavenger.

PMID- 22955047
TI  - Liposome and protein-water partitioning of polybrominated diphenyl ethers
      (PBDEs).
AB  - Bioaccumulation of polybrominated diphenyl ethers (PBDEs) in marine and
      terrestrial organisms is of great environmental concern. Understanding the
      partitioning of PBDEs to biological phases is crucial for elucidating their
      bioaccumulation behavior. In this study, partitioning coefficients of PBDEs from
      water to phospholipid liposomes (K(lipw)) and to bovine serum albumin (BSA)
      (K(BSAw)) were measured using a polymer depletion method. K(lipw) values measured
      in two laboratories are in an excellent agreement (within 0.14 log units),
      indicating a high method repeatability. The values of log K(lipw) and log K(BSAw)
      are in the range of 6.3-8.2 and 5.1-7.0, respectively, representing the highest
      of these partition coefficients measured to date. Log K(lipw) values for PBDEs
      are similar to the log of the octanol-water partition coefficients (K(ow)) (log
      K(lipw)-log K(ow)=-0.06+/-0.23; mean+/-SD of 7 congeners), consistent with the
      data of chlorobenzenes and polychlorinated biphenyls (PCBs) reported in the
      literature. No hydrophobicity cutoff was observed for partitioning to the
      liposome membrane. Log K(BSAw) values for PBDEs increase linearly with log K(ow)
      and do not follow the non-linear trend observed for polycyclic aromatic
      hydrocarbons (PAHs). This difference between PBDEs and PAHs suggests specific
      binding mechanisms to serum albumin even for hydrophobic compounds.

PMID- 22955048
TI  - Distributions and bioconcentration characteristics of perfluorinated compounds in
      environmental samples collected from the west coast of Korea.
AB  - As part of an ongoing study of the status and trends of contaminants in the
      Yellow Sea, during May of 2009, the concentrations of perfluorinated compounds
      (PFCs) were determined in water (n=15), sediment (n=12), soil (n=13), and biota
      (n=74) from estuarine and coastal areas along the west coast of Korea. Of the
      12PFCs monitored, PFOS and PFOA were the most frequently detected compounds in
      water. Greater concentrations of PFCs were found in waters from the inner regions
      of sea dikes in three artificial lakes, Shihwa, Asan, and Sapgyo, than outer
      regions. Concentrations were also comparable in two estuarine areas, which
      indicated that most PFCs in coastal areas originated from industrial and local
      regions and river water flowing through estuaries. Concentrations of PFCs in
      soils and sediments were generally less than limits of quantification and were
      generally less than those measured in biota. Compound-specific bioaccumulation of
      PFBS and PFOS had the greatest BCF values in crab, while in fish it was PFOS and
      PFDA, and in gastropods and bivalves it was PFHxS. Distributions of BCFs for PFOS
      in body-parts of crab showed the greatest values in soft tissues followed by
      shells and then legs. Distribution among tissues and organs of fishes was more
      variable than those observed for crab. When compared to a similar study conducted
      by our group in 2008, concentrations of PFCs in water samples were significantly
      less in 2009. However, there was little change in bioconcentration from sediments
      into benthic organisms. Finally, we conducted the assessment of potential adverse
      effects for PFCs on aquatic life by use of current and previous reported data.

PMID- 22955049
TI  - On the ranking of chemicals based on their PBT characteristics: comparison of
      different ranking methodologies using selected POPs as an illustrative example.
AB  - Knowledge of the environmental behavior of chemicals is a fundamental part of the
      risk assessment process. The present paper discusses various methods of ranking
      of a series of persistent organic pollutants (POPs) according to the persistence,
      bioaccumulation and toxicity (PBT) characteristics. Traditionally ranking has
      been done as an absolute (total) ranking applying various multicriteria data
      analysis methods like simple additive ranking (SAR) or various utility functions
      (UFs) based rankings. An attractive alternative to these ranking methodologies
      appears to be partial order ranking (POR). The present paper compares different
      ranking methods like SAR, UF and POR. Significant discrepancies between the
      rankings are noted and it is concluded that partial order ranking, as a method
      without any pre-assumptions concerning possible relation between the single
      parameters, appears as the most attractive ranking methodology. In addition to
      the initial ranking partial order methodology offers a wide variety of analytical
      tools to elucidate the interplay between the objects to be ranked and the ranking
      parameters. In the present study is included an analysis of the relative
      importance of the single P, B and T parameters.

PMID- 22955050
TI  - Time to intervene: lessons from the NCEPOD report.

PMID- 22955051
TI  - Changes and their prognostic implications in the abbreviated VitalpacTM early
      warning score (ViEWS) after admission to hospital of 18,853 acutely ill medical
      patients.
AB  - BACKGROUND: The best performing early warning score is VitalpacTM Early Warning
      Score (ViEWS). However, it is not known how often, to what extent and over what
      time frame any early warning scores change, and what the implications of these
      changes are. SETTING: Thunder Bay Regional Health Sciences Center, Ontario,
      Canada. METHODS: The changes in the first three complete sets of the six
      variables required to retrospectively calculate the abbreviated version of ViEWS
      (that did not include mental status) after admission to hospital of 18,853
      acutely ill medical patients, and their relationship to subsequent in-hospital
      mortality were examined. RESULTS: In the 10.4 SD 20.1 (median 5.0) hours between
      admission and the second recording the score changed in only 5.9% of patients and
      these changes were of no prognostic value. By the time of the third recording
      34.9 SD 21.7 (median 30.0) hours after admission a change in score was clearly
      associated with a corresponding change in in-hospital mortality (e.g. for
      patients with an initial score of 5 an increase between the first and third
      recording of >=4 points was associated with an increased mortality (OR 6.5 95% CI
      2.3-15.9, p<0.00001), whereas a reduction of <=-4 points was associated with a
      reduced mortality (OR 0.4 95% CI 0.2-0.9, p 0.03)). CONCLUSION: After a median
      interval of 30 h both the initial abbreviated ViEWS recording and subsequent
      changes in it both predict clinical outcome. It remains to be determined what
      interventions during this time frame will improve patient outcomes.

PMID- 22955052
TI  - Delivery of titrated oxygen via a self-inflating resuscitation bag.
AB  - AIM: To investigate whether titration of inspired oxygen can be achieved through
      adjustment of oxygen flow into a self-inflating resuscitation bag with a
      reservoir of a type used in standard ambulance practice. METHODS: In a series of
      bench experiments, oxygen was delivered via a flow metre to a 1500 ml self
      inflating resuscitation bag with a 2500 ml reservoir bag and connected to a test
      lung. The oxygen concentration delivered to the test lung by manual inflation of
      the resuscitation bag was measured using an anaesthetic machine while the
      delivered tidal volume was measured using a respirometer. The delivered oxygen
      concentration was measured at flows of 0.5, 2, 6, 12 and 15 l min(-1) for tidal
      volumes of 300, 600, and 900 ml with bag inflation rates of 10, 20 and 30 min(
      1). RESULTS: A wide range of delivered oxygen concentrations ranging between 24%
      and 99.5% were achieved with different oxygen flows, tidal volumes, and inflation
      rates. Overall, the mean delivered oxygen concentration increased significantly
      with each of the increments of oxygen flow tested (p<0.001 for all comparisons).
      CONCLUSIONS: Effective titration of oxygen delivery can be achieved using
      adjustment of oxygen flow with a standard self-inflating resuscitation bag and
      reservoir.

PMID- 22955053
TI  - Scaling up pediatric HIV care and treatment in Africa: clinical site
      characteristics associated with favorable service utilization.
AB  - BACKGROUND: To improve pediatric enrollment and retention in HIV treatment
      programs in Africa, we examined factors associated with service utilization
      within the Elizabeth Glaser Pediatric AIDS Foundation program in Cote d'Ivoire,
      Mozambique, South Africa, Tanzania and Zambia. METHODS: We retrospectively
      reviewed characteristics of clinical sites providing HIV treatment services
      within our program. For each site, favorable pediatric program outcomes were
      defined as a cumulative number or percentage of pediatric enrollment in care or
      antiretroviral therapy (ART) more than the pooled median value or an attrition
      rate less than 10%. We compared proportions of sites with favorable outcomes
      among those with or without selected characteristics. Adjusted odds ratios (aORs)
      and 95% confidence intervals (CIs) were determined using logistic regression
      analyses, accounting for potential confounding factors. RESULTS: Over 4 years,
      33,331 children were enrolled, including 18,255 on ART, across 220 sites.
      Characteristics associated with favorable pediatric enrollment were nutritional
      support (aOR = 8.9; CI: 2.8 to 28.4), linkages with associations of people living
      with HIV (aOR = 4.2; CI: 1.8 to 9.5), early infant diagnosis (aOR = 3.3; CI: 1.5
      to 7.1), and on-site prevention of mother-to-child transmission services (aOR =
      3.1; CI: 1.0 to 11.1). Similarly, linkages with people living with HIV, early
      infant diagnosis, and prevention of mother-to-child transmission were associated
      with high proportion of children on ART younger than 2 years of age. Home-based
      care was associated with low pediatric attrition rates (aOR = 2.9; CI: 1.4 to
      5.8). CONCLUSIONS: Certain site characteristics were associated with favorable
      pediatric enrollment and retention in our program. Expanding these
      characteristics to improve pediatric HIV treatment in Africa warrants further
      evaluation.

PMID- 22955054
TI  - Alcohol consumption and CD4 T-cell count response among persons initiating
      antiretroviral therapy.
AB  - BACKGROUND: We evaluated the longitudinal association of alcohol use with
      immunologic response to combination antiretroviral therapy (ART) among HIV
      infected individuals. METHODS: This was a prospective cohort study of individuals
      initiating ART. Participants underwent an Audio Computer-Assisted Self-interview
      querying drug and alcohol use within 6 months of treatment. Immunologic response
      to ART was defined by CD4 T-cell count (CD4). Primary independent variables were
      self-reported number of drinks consumed per drinking day (quantity) and days of
      alcohol consumption in a typical week (frequency). We used linear mixed effects
      models to quantify the association between CD4 T-cell count and alcohol quantity
      and frequency and Cox proportional hazards models to estimate the relative hazard
      of an increase in 100, 150, and 200 CD4 cells per cubic millimeter per additional
      drink per drinking day. Analyses were stratified by sex. Viral suppression was
      examined as a time-varying covariate. RESULTS: Between 2000 and 2008, 1107
      individuals were eligible for inclusion in this study. There was no statistically
      significant difference in CD4 T-cell count by average drinks per drinking day at
      any frequency of alcohol use irrespective of sex or viral suppression. Similarly,
      we found no difference in the hazard ratio for drinks per drinking day within the
      categories of drinking frequency for time to CD4 T-cell count increase of 100,
      150, and 200 cells per cubic millimeter, respectively. CONCLUSIONS: Among
      individuals initiating ART, the benefits of therapy and viral suppression on the
      immune system outweigh detrimental effects of alcohol, reinforcing the importance
      of initiating ART and ensuring adequate adherence to therapy.

PMID- 22955055
TI  - Synchronization of beta and gamma oscillations in the somatosensory evoked
      neuromagnetic steady-state response.
AB  - The sensory evoked neuromagnetic response consists of superimposition of an
      immediately stimulus-driven component and induced changes in the autonomous brain
      activity, each having distinct functional relevance. Commonly, the strength of
      phase locking in neural activities has been used to differentiate the different
      responses. The steady-state response is a strong oscillatory neural activity,
      which is evoked with rhythmic stimulation, and provides an effective tool to
      investigate oscillatory brain networks. In this case, both the sensory response
      and intrinsic activity, representing higher order processes, are highly
      synchronized to the stimulus. In this study we hypothesized that temporal
      dynamics of oscillatory activities would characterize the differences between the
      two types of activities and that beta and gamma oscillations are differently
      involved in this distinction. We used magnetoencephalography (MEG) for studying
      how ongoing steady-state responses elicited by a 20-Hz vibro-tactile stimulus to
      the right index finger were affected by a concurrent isolated touch stimulus to
      the same hand ring finger. SI source activity showed oscillations at multiples of
      20 Hz with characteristic differences in the beta band and the gamma band. The
      response amplitudes were largest at 20 Hz (beta) and significantly reduced at 40
      Hz and 60 Hz (gamma), although synchronization strength, indicated by inter-trial
      coherence (ITC), did not substantially differ between 20 Hz and 40 Hz. Moreover,
      the beta oscillations showed a fast onset, whereas the amplitude of gamma
      oscillations increased slowly and reached the steady state 400 ms after onset of
      the vibration stimulus. Most importantly, the pulse stimuli interacted only with
      gamma oscillations in a way that gamma oscillations decreased immediately after
      the concurrent stimulus onset and recovered slowly, resembling the initial slope.
      Such time course of gamma oscillations is similar to our previous observations in
      the auditory system. The time constant is in line with the time required for
      conscious perception of the sensory stimulus. Based on the observed different
      spectro-temporal dynamics, we propose that while beta activities likely relate to
      independent representation of the sensory input, gamma oscillation likely relates
      to binding of sensory information for higher order processing.

PMID- 22955056
TI  - Reactive oxygen species are not a required trigger for exercise-induced late
      preconditioning in the rat heart.
AB  - Reactive oxygen species (ROS) have been reported to play a primary role in
      triggering the cardioprotective adaptations by some preconditioning procedures,
      but whether they are required for exercise-induced preconditioning is unclear.
      Thus in this study we used the free radical scavenger N-(2
      mercaptopropionyl)glycine (MPG) to test the hypothesis that ROS is the trigger
      for exercise-induced preconditioning of the heart against ischemia-reperfusion
      injury. Male F344 rats were assigned to four groups: sedentary (SED, n = 7),
      SED/MPG (100 mg/kg ip daily for 2 days, n = 12), exercised on a treadmill for 2
      days at 20 m/min, 6 degrees  grade, for 60 min (RUN, n = 7), and RUN/MPG with 100
      mg/kg MPG injected 15 min before exercise (n = 10). Preliminary experiments
      verified that MPG administration maintained myocardial redox status during the
      exercise bout. Twenty-four hours postexercise or MPG treatment isolated perfused
      working hearts were subjected to global ischemia for 22.5 min followed by
      reperfusion for 30 min. Recovery of myocardial external work (percentage of
      preischemic systolic pressure times cardiac output) for SED (50.4 +/- 4.5) and
      SED/RUN (54.7 +/- 6.6) was similar and improved in both exercise groups (P <
      0.05) to 77.9 +/- 3.0 in RUN and 76.7 +/- 4.5 in RUN/MPG. A 2 * 2 ANOVA also
      revealed that exercise decreased lactate dehydrogenase release from the heart
      during reperfusion (marker of cell damage) without MPG effects or interactions.
      Expression of the cytoprotective protein inducible heat shock protein 70
      increased by similar amounts in the left ventricles of RUN and RUN/MPG compared
      with sedentary groups (P < 0.05). We conclude that ROS are not a necessary
      trigger for exercise-induced preconditioning in rats.

PMID- 22955057
TI  - RhoA localization with caveolin-1 regulates vascular contractions to serotonin.
AB  - Vascular smooth muscle contraction occurs following an initial response to an
      increase in intracellular calcium concentration and a sustained response
      following increases in the sensitivity of contractile proteins to calcium
      (calcium sensitization). This latter process is regulated by the rhoA/rho kinase
      pathway and activated by serotonin. In multiple cell types, signaling molecules
      compartmentalize within caveolae to regulate their activation. We hypothesized
      that serotonin differentially compartmentalizes rhoA within caveolar versus
      noncaveolar lipid rafts to regulate sustained vascular contractions. To test this
      hypothesis, we measured aortic contractions in response to serotonin in wild-type
      (WT) and cav-1-deficient mice (cav-1 KO). RhoA-dependent contractions in response
      to serotonin were markedly augmented in arteries from cav-1 KO mice despite a
      modest reduction in rhoA expression compared with WT. We found that under basal
      conditions, rhoA in WT arteries was primarily localized within high-density
      sucrose gradient fractions but temporally shifted to low-density fractions in
      response to serotonin. In contrast, rhoA in cav-1 KO arteries was primarily in
      low-density fractions and shifted to high-density fractions in a similar
      timeframe as that seen in WT mice. We conclude that localization of rhoA to
      caveolar versus noncaveolar lipid rafts differentially regulates its activation
      and contractions to rhoA-dependent agonists with greater activation associated
      with its localization to noncaveolar rafts. Disruption of rhoA localization
      within caveolae may contribute to increased activation and enhanced vascular
      contractions in cardiovascular disease.

PMID- 22955059
TI  - Autologous incubated macrophage treatment failed to show a difference in the
      neurological outcome in patients with acute, complete spinal cord injury.

PMID- 22955058
TI  - Responses of neurons in the caudal medullary lateral tegmental field to visceral
      inputs and vestibular stimulation in vertical planes.
AB  - The dorsolateral reticular formation of the caudal medulla, or the lateral
      tegmental field (LTF), has been classified as the brain's "vomiting center", as
      well as an important region in regulating sympathetic outflow. We examined the
      responses of LTF neurons in cats to rotations of the body that activate
      vestibular receptors, as well as to stimulation of baroreceptors (through
      mechanical stretch of the carotid sinus) and gastrointestinal receptors (through
      the intragastric administration of the emetic compound copper sulfate).
      Approximately half of the LTF neurons exhibited graviceptive responses to
      vestibular stimulation, similar to primary afferents innervating otolith organs.
      The other half of the neurons had complex responses, including spatiotemporal
      convergence behavior, suggesting that they received convergent inputs from a
      variety of vestibular receptors. Neurons that received gastrointestinal and
      baroreceptor inputs had similar complex responses to vestibular stimulation; such
      responses are expected for neurons that contribute to the generation of motion
      sickness. LTF units with convergent baroreceptor and vestibular inputs may
      participate in producing the cardiovascular system components of motion sickness,
      such as the changes in skin blood flow that result in pallor. The administration
      of copper sulfate often modulated the gain of responses of LTF neurons to
      vestibular stimulation, particularly for units whose spontaneous firing rate was
      altered by infusion of drug (median of 459%). The present results raise the
      prospect that emetic signals from the gastrointestinal tract modify the
      processing of vestibular inputs by LTF neurons, thereby affecting the probability
      that vomiting will occur as a consequence of motion sickness.

PMID- 22955060
TI  - Induced genome maintenance pathways in pre-cancer tissues describe an anti-cancer
      barrier in tumor development.
AB  - A recent model proposing that a barrier is raised against tumor evolution in pre
      cancer tissues is investigated. For that we quantify expression alterations in
      genome maintenance pathways: DNA damage response, death pathways and cell cycle
      and also differentially expressed genes in transcriptomes of pre-cancerous and
      cancerous lesions deposited in the GEO database. We find that the main
      alterations in pre-cancer samples comprising the barrier are: (1) DNA double
      strand-breaks signaling and repair pathways induction, (2) upregulation of cyclin
      dependent kinases, (3) p53 dependent (and independent) repair and apoptosis
      pathways induction and (4) replicative senescence induction early in tissue
      transformation. In the cancer samples we find that the induced pathways in pre
      cancer are systematically inhibited and the only remaining induced pathway is
      p53, whereas the retinoblastoma pathway arises induced in most samples. The
      results give support to the model, furthermore they reveal the involvement of
      additional mechanisms in pre-cancer, including the early induction of replicative
      senescence and of p53 independent apoptosis.

PMID- 22955061
TI  - 4,4'-Bithiazole-based tetraarylenes: new photochromes with unique photoreactive
      patterns.
AB  - Five 4,4'-bithiazole-based tetraarylenes were prepared and their photochromic
      behavior investigated. With their 1,3,5,7-octatetraene photoreactive backbone,
      they offer not only more available sites for further functionalizations, but also
      a novel design principle for the development of a new class of biphotochromes.

PMID- 22955062
TI  - Excited states of menthyl anthranilate: a UV-A absorber.
AB  - The photophysical properties of menthyl anthranilate (MA), a UV-A absorber, have
      been studied through measurements of UV absorption, fluorescence, triplet-triplet
      absorption and time-resolved thermal lens in ethanol at room temperature and/or
      77 K. The phosphorescence and time-resolved electron paramagnetic resonance
      spectra have also been observed in ethanol at 77 K. The energy levels of the
      lowest excited singlet (S(1)) state and triplet (T(1)) state were determined. The
      quantum yields of fluorescence, phosphorescence and S(1) -> T(1) intersystem
      crossing (ISC) were also determined. From the data on the lifetime and quantum
      yield, the rate constants of the radiative decay, internal conversion and ISC of
      the excited states of MA were determined. The exceptionally high ISC quantum
      yield of MA shows that the deactivation processes of the S(1) state of MA are
      different from those of most UV absorbers such as cinnamate, salicylate, 2
      hydroxybenzophenone, benzotriazole and dibenzoylmethane derivatives, where the
      internal conversion rates of the S(1) states are much faster than the ISC rates.
      The observed T(1) lifetime and zero-field splitting parameters suggest that the
      T(1) state of MA possesses almost pure (3)pipi* character.

PMID- 22955063
TI  - Synthesis, characterization and biocompatibility evaluation of iron oxide
      incorporated magnetic mesoporous silica.
AB  - On the basis of a thermal process, a facile, low cost, one-step approach for
      preparing iron oxide (Fe(2)O(3)) incorporated ordered magnetic mesoporous silica
      nanocomposites by a co-operative self-assembly approach is presented. Various
      mesostructured silica materials incorporated with different amounts of iron oxide
      (nSi/nFe = 1/1, 1/0.5, 1/0.25 and 1/0.123) at various pH (<1, 3, 5 and 7) were
      synthesized and characterized by electron microscopy and X-ray diffractometry.
      Further, the surface area and magnetic properties were evaluated using N(2)
      sorption analyses, and a superconducting quantum interference device interfaced
      with a vibrating sample magnetometer (SQUID-VSM) respectively. The transmission
      electron micrographs and nitrogen sorption analysis indicated that most of the
      Fe(2)O(3) domains of several nanometers were embedded in the silica walls, rather
      than dispersed in the mesopores. The incorporation of iron oxide into the
      mesopores without compromising the structural and textural properties was
      achieved at pH < 1. These structures have great potential in diagnostics and
      therapeutics. However, the acceptance of this material by the biological host is
      a critical issue for such biomedical applications. In this study, we have also
      evaluated the in vivo biocompatibility of these magnetic mesoporous materials in
      a rat model. The histopathological results show that this magnetic material can
      be classified as a level 2 biomaterial that can be safely used for short term
      applications such as MRI imaging, hyperthermia, targeted drug delivery, etc.

PMID- 22955064
TI  - Separating uncertainty and physiological variability in human PBPK modelling: The
      example of 2-propanol and its metabolite acetone.
AB  - Parameter uncertainty and interindividual variability in the predictions of a
      generic human physiologically based pharmacokinetic (PBPK) model were separated
      by means of nested Monte Carlo simulations. Separate information on uncertainty
      and variability can help decision makers to identify whether they should focus on
      identification of sensitive individuals rather than on additional research to
      obtain more accurate estimates for particular parameters. In this study, the
      concentration of acetone in human blood was simulated during and after 4h of
      exposure to 2-propanol via air. It was shown that the influence of
      interindividual variability and uncertainty varies over time, from the uptake
      phase, via a steady-state phase, into the elimination phase. During the uptake
      phase, interindividual variability played a significant role in the predicted
      variation of acetone concentrations in blood, with variability up to a factor of
      2-3 (90th/10th percentile ratio). After exposure ceased, the parameter
      uncertainty increased up to a factor of 100 after 16h, whereas variability
      remained unchanged. Parameter importance analysis indicated that variability in
      human physiology had the largest influence on predicted acetone concentrations in
      blood during exposure. Uncertainty in the metabolic rate of acetone was most
      important after the exposure had ceased and overruled variability.

PMID- 22955065
TI  - Sparsity regularization in dynamic elastography.
AB  - We consider the inverse problem of continuum mechanics with the tissue
      deformation described by a mixed displacement-pressure finite element
      formulation. The mixed formulation is used to model nearly incompressible
      materials by simultaneously solving for both elasticity and pressure
      distributions. To improve numerical conditioning, a common solution to this
      problem is to use regularization to constrain the solutions of the inverse
      problem. We present a sparsity regularization technique that uses the discrete
      cosine transform to transform the elasticity and pressure fields to a sparse
      domain in which a smaller number of unknowns is required to represent the
      original field. We evaluate the approach by solving the dynamic elastography
      problem for synthetic data using such a mixed finite element technique, assuming
      time harmonic motion, and linear, isotropic and elastic behavior for the tissue.
      We compare our simulation results to those obtained using the more common
      Tikhonov regularization. We show that the sparsity regularization is less
      dependent on boundary conditions, less influenced by noise, requires no parameter
      tuning and is computationally faster. The algorithm has been tested on magnetic
      resonance elastography data captured from a CIRS elastography phantom with
      similar results as the simulation.

PMID- 22955066
TI  - Calculation of renal differential function following renal transplant:
      retrospective validation of a simplified method.
AB  - OBJECTIVES: The estimation of differential function (DF) in post-renal transplant
      patients (PRTPs) is challenging because of the different distances of the native
      kidneys (NKs) and transplant kidney (TK) to the gamma camera and because current
      commercial software allows evaluation of only 2 kidneys instead of 3. We
      retrospectively validated a simplified method (SM) to process renal scans and
      hypothesized that it is comparable with the reference method (RM). PATIENTS AND
      METHODS: Twelve 99mTc MAG3 renal scintigraphies of 10 PRTPs were performed on a
      dual-head gamma camera. The RM was a 2-step process, with the left and right NKs
      being compared with the TK separately. The SM was a 1-step process combining both
      NKs together. The DF estimates were consistent with geometric means in both
      methods. Statistical evaluation included linear correlation and Bland-Altman
      analysis. RESULTS: The RM and SM showed DF of 78% +/- 25% versus 79% +/- 27% for
      the TK and 22% +/- 25% versus 21% +/- 27% for the NKs (P = 0.3). There was
      excellent correlation between SM and RM measurements (r = 0.99, P < 0.001). Bland
      Altman plot demonstrated a mean difference of 1.2 +/- 3.8 at a 95% confidence
      interval (95% CI) of agreement of -6.2 to + 8.5 for the TK and -1.2 +/- 3.8 at a
      95% CI of agreement of -8.5 to + 6.2 for the NKs. Only 1 (8%) of 12 scans showed
      a difference slightly beyond the 95% CI, indicating a good agreement between SM
      and RM. CONCLUSIONS: The SM offers a simple way to evaluate renal DF in PRTP and
      shows comparable results with the RM. It may have great potential in clinical
      practice; however, larger studies are needed to verify and further extend the
      results of this study.

PMID- 22955067
TI  - Is FDG PET a better imaging tool than somatostatin receptor scintigraphy in
      patients with relapsing multiple myeloma?
AB  - PURPOSE: Osseous involvement defined by lytic bone lesions is shown by skeletal
      survey in multiple myeloma (MM). This technique has limitations because it
      detects only lesions with more than 30% trabecular bone loss. In addition,
      lesions persist after chemotherapy, thereby limiting its usefulness at relapsing
      disease. Alternative techniques to detect new bone lesions are somatostatin
      receptor scintigraphy (SRS) and 18F-fluordeoxyglucose (FDG) PET so far
      predominantly studied in patients with newly diagnosed MM. Malignant plasma cells
      can have a high expression of somatostatin receptors and an elevated metabolic
      activity. Therefore, these techniques might be useful in patients with relapsing
      MM because they are not hampered by preexisting skeletal defects. The purpose of
      this study was to demonstrate which technique is most optimal to detect skeletal
      lesions in patients with relapsing MM. METHOD: In patients with relapsing MM (n =
      21), 3 separate methods were used (skeletal survey, SRS, and FDG PET) for
      detecting new skeletal lesions. RESULTS: Of all patients, 55% had new lesions on
      the skeletal survey [mean (SD), 1.45 (1.76); range, 0-5], 52% had new SRS lesions
      [mean (SD), 1.43 (0.38); range, 0-5], and 71% demonstrated new lesions on the FDG
      PET-scan [mean (SD), 4.05 (0.9); range, 0-12]. The lesions on skeletal survey and
      SRS corresponded with FDG PET. The number of lesions was higher with the FDG PET
      versus that with SRS (P = 0.01) and with FDG PET versus that with skeletal survey
      (P = 0.01). CONCLUSIONS: The results demonstrate that FDG PET is more valuable
      than skeletal survey and SRS to detect disease activity in relapsing MM.

PMID- 22955068
TI  - 18F-FDG uptake changes in liver and mediastinum during chemotherapy in patients
      with diffuse large B-cell lymphoma.
AB  - PURPOSE: The main objective of this study was to assess the intrasubject and
      intersubjects variability of 18F-FDG uptake in liver (LIV) and mediastinum (MBP)
      among patients with diffuse large B-cell lymphoma (DLBCL), treated with different
      chemotherapy regimens. PATIENTS AND METHODS: Fifty patients with DLBCL who
      underwent 18F-FDG PET/CT scan at baseline, after a few cycles of therapy (interim
      PET) and on completion of therapy (final PET), were enrolled retrospectively.
      SUVmean and SUVmax values for LIV and MBP, their differences (LIV - MBP SUVmean
      and LIV - MBP SUVmax), and their changes were calculated, respectively. RESULTS:
      Liver uptake significantly increased in the interim in comparison with baseline
      and final PET, respectively, whereas MBP activity remained stable during
      chemotherapy. The intersubject variability of 18F-FDG uptake in LIV and MBP
      ranged from 20.2% to 25.4%. CONCLUSIONS: The variability of the LIV uptake during
      chemotherapy should be taken into account when this parameter is used to score
      the interim PET scan and to make decisions in defining response-adapted
      therapeutic strategies. Vice versa, the stability of MBP activity during therapy
      provides a more reliable benchmark for the response assessment.Finally, the
      intersubjects variability of both parameters should be considered when the visual
      evaluation of the interim PET is performed by point score models.

PMID- 22955069
TI  - Longer intervals between hematopoietic stem cell transplantation and subsequent
      90Y-ibritumomab radioimmunotherapy may correlate with better tolerance.
AB  - PURPOSE: This study aimed to evaluate the efficacy and toxicity of
      radioimmunotherapy (RIT) in recurrent lymphoma after hematopoietic stem cell
      transplantation (HSCT). METHODS: We reviewed 9 patients, 7 with follicular
      lymphoma (DLBCL), 1 with mantle cell lymphoma (MCL), and 1 with diffuse large B
      cell lymphoma treated with 90Y-ibritumomab tiuxetan 6 to 140 months after HSCT.
      Patients underwent 111In-ibritumomab scintigraphy and were treated 1 week later
      with standard 14.8 MBq/kg (n = 4) or 11.1 MBq/kg (n = 4) 90Y-ibritumomab. One
      patient who had allo-HSCT had reduced activity (70%) treatment. RESULTS: Among
      the 7 FL patients, we observed complete response (CR) in 2 patients and partial
      response (PR) in 5 patients. One patient with CR relapsed after 15 months; the
      other persisted 43.5 months after RIT. Of 5 patients with PR, 3 relapsed between
      13 and 17 months; 1 persisted until unrelated death at 11.5 months. The fifth
      patient with PR received adoptive immunotherapy and improved to metabolic (FDG
      PET) CR that persists 45.5 and 41 months after 90Y-ibritumomab and immunotherapy,
      respectively. Patients with MCL and DLBCL progressed or experienced stabilization
      (5 months), respectively. Six patients had grade 1 to 3 bone marrow (BM) toxicity
      and recovered within 3 months. Three patients having 90Y-ibritumomab 6, 14, and
      24 months after HSCT experienced grade 4 BM toxicity. One of them (RIT 24 months
      after HSCT) recovered after 3 months, another delayed after 9 months, and the
      third patient only partially recovered, eventually developed myelodysplasia, and
      was allografted. CONCLUSIONS: Radioimmunotherapy after HSCT is an effective
      rescue therapy in FL. However, BM toxicity may be important; 3 of 8 patients
      treated with standard 90Y-ibritumomab activity experienced grade 4 BM toxicity,
      with incomplete recovery 3 months after RIT in 2 patients, both treated early (6
      and 14 months) after HSCT.

PMID- 22955070
TI  - Relationship between myocardial perfusion-gated SPECT and the performance of
      coronary revascularization in patients with ischemic cardiomyopathy.
AB  - PURPOSE: Ischemic cardiomyopathy (ICM) is a disease with high morbidity and
      mortality. There are several published studies on the evolution and prognosis of
      patients with ICM. However, reports on the therapeutic management in clinical
      practice are scarce. The aim of this study was to analyze coronary
      revascularization (CR) performance in patients with ICM and suitable coronary
      anatomy according to myocardial perfusion stress-rest gated SPECT results.
      PATIENTS AND METHODS: Eighty-seven consecutive patients (mean age, 62.4 y; 20
      women), with ischemic heart disease, left ventricular ejection fraction of 40% or
      less, coronary anatomy suitable for CR, and without previous CR, were evaluated
      by means of stress-rest gated SPECT. RESULTS: Sixty-four percent of patients had
      scintigraphic criteria of viability and 62.1% showed scintigraphic ischemia in
      stress-rest gated SPECT. Forty-five percent of patients were revascularized, and
      the remainder received medical treatment only. Coronary revascularization was
      more frequent in patients with scintigraphic viability (P = 0.012), in those with
      scintigraphic ischemia (P = 0.007), and in those with low left ventricular end
      systolic volume (P = 0.006). Cox regression analysis identified multivessel
      disease [hazard ratio (HR), 3.3; 95% confidence interval (CI), 4-7.8], summed
      difference score greater than 4 (HR, 3.9; 95% CI, 1.5-9.8), and left ventricular
      end-systolic volume less than 120 mL (HR, 3.2; 95% CI, 1.3-8.2) as the best
      independent predictors of CR treatment. CONCLUSIONS: In patients with ICM and
      suitable coronary arteries who are able to perform a stress myocardial perfusion
      gated SPECT, the presence of multivessel disease and myocardial ischemia and the
      absence of severely increased left ventricular volume were associated to a
      decision of CR.

PMID- 22955071
TI  - Early CT compared with bone scintigraphy in suspected schapoid fractures.

PMID- 22955072
TI  - Asymptomatic giant arachnoid cyst.
AB  - A 51-year-old male bricklayer without cerebral symptoms underwent whole-body FDG
      PET for suspicion of mediastinal sarcoidosis. PET/CT incidentally demonstrated a
      voluminous right frontal arachnoid cyst with normal glucose metabolism in the
      adjacent cortex. MRI demonstrated compression of the ipsilateral cerebral
      parenchyma and precentral, angulate, callosal, and superior frontal sulci.
      Functional bilateral finger-thumb paradigm MRI revealed right hemispheric
      reorganization of cortical motor activation with prominent activation between the
      inferior frontal gyrus and the postcentral gyrus.

PMID- 22955073
TI  - 18F-FDG PET/CT in a patient affected by renal collecting duct (Bellini)
      carcinoma.
AB  - Renal collecting duct (Bellini) carcinoma is a very rare variant of renal cell
      carcinoma. It is associated with a poor prognosis and is often metastatic at the
      time of diagnosis. We report a case of a 44-year-old man affected by Bellini
      carcinoma, who underwent postoperative staging with 18F-FDG PET/CT. It revealed
      high tracer uptake at multiple lymph nodal metastases.

PMID- 22955074
TI  - Unusual isolated perineal recurrence in mucinous adenocarcinoma of the rectum
      after abdominoperineal resection: usefulness of dual-time-point FDG PET in
      evaluating mucinous tumors.
AB  - Application of dual-time-point FDG PET for mucinous adenocarcinoma has been
      rarely reported. Isolated perineal recurrence (after neoadjuvant
      chemoradiotherapy and abdominoperineal resection) was detected by dual-time-point
      FDG PET in a 41-year-old man with mucinous adenocarcinoma of the rectum.
      Correlative contrast-enhanced CT demonstrated circumscribed lobulated mass in the
      fatty tissue of the right perineal region, which was metastatic adenocarcinoma,
      on fine needle aspiration cytology. An SUVmax increase with time is consistently
      observed in mucinous tumors.

PMID- 22955075
TI  - FDG PET/CT findings in acquired perforating dermatosis.
AB  - Acquired perforating dermatosis (APD) is an uncommon cutaneous perforating
      disorder. We report a patient on hemodialysis who developed skin eruption and
      jaundice. He underwent FDG PET/CT under suspicion of biliary malignancies. PET/CT
      showed no significant abnormal uptake except of multiple FDG-avid nodules in the
      skin. The eruption he had was histopathologically diagnosed as APD by skin
      biopsy. His case suggests that APD should be considered as a differential
      diagnosis when multiple cutaneous FDG accumulations are found in a patient on
      hemodialysis. To the best of our knowledge, this is the first report showing the
      FDG PET/CT findings of APD.

PMID- 22955076
TI  - Parotid gland metastasis from squamous cell carcinoma of esophagus detected by
      FDG PET/CT.
AB  - A 55-year-old man was diagnosed with squamous cell carcinoma in the middle
      thoracic esophagus. The FDG PET/CT revealed an incidental strong FDG-avid finding
      (SUVmax, 11) in the right parotid gland, which was subsequently confirmed as
      metastasis from the squamous cell carcinoma of esophagus via surgery. The current
      case adds another differential diagnosis of parotid FDG-avid lesion to the
      existing literature.

PMID- 22955077
TI  - Unsuspected pneumonia detected by increased lung uptake on 111In-ibritumomab
      tiuxetan scan.
AB  - 99Y-ibritumomab tiuxetan (Zevalin) is a CD20-targeted radioimmunotherapy for the
      treatment of B-cell non-Hodgkin lymphoma approved by the FDA in 2002. The
      acquisition of an 111In ibritumomab tiuxetan scan (bioscan) to confirm normal
      biodistribution before treatment with 99Y-ibritumomab tiuxetan was initially
      required in the United States until November 2011. This is the first documented
      example of abnormal biodistribution due to unsuspected pneumonia detected by
      increased lung uptake on the bioscan. The pneumonia was treated and resolved
      before 99Y Zevalin, avoiding potential harm and indicating that a screening chest
      x-ray may be appropriate when a bioscan is not performed.

PMID- 22955078
TI  - Spontaneous perforation of common bile duct in a pediatric patient: application
      of hepatobiliary scintigraphy.
AB  - We report a case of spontaneous biliary perforation in a 21-month old female
      pediatric patient with the presenting symptoms of abdominal distension, jaundice,
      and umbilical hernia. Hepatobiliary scintigraphy showed tracer accumulation in
      the peritoneal cavity. Preliminary diagnosis of spontaneous biliary perforation
      was confirmed during surgery. After surgical repair of the biliary leakage, the
      patient recovered fully. This case shows the importance of hepatobiliary
      scintigraphy in patients suspicious for this condition.

PMID- 22955079
TI  - Vesicovaginorectal fistula on a FDG PET/CT of a patient with recurrent cervical
      cancer and end-stage renal disease.
AB  - A 59-year-old woman with recurrent cervical cancer and end-stage renal disease
      was referred for FDG PET/CT for restaging. The patient had hemodialysis for 4
      years and radiotherapy 3 years ago and 1 year ago. The PET/CT scan showed
      recurrent cervical cancer and intense FDG radioactivity in the urinary bladder,
      with a small air bubble in both the urinary bladder and the vagina. After supine
      positioning without voiding, the delayed images showed more air bubbles with less
      FDG activity in the urinary bladder. The vesicovaginorectal fistula was confirmed
      by surgery.

PMID- 22955080
TI  - Recurrent and metastatic osteoclast-like giant cell tumor of the liver revealed
      by FDG PET/CT.
AB  - A 38-year-old woman presented with nausea and abdominal distension 15 months
      after surgical resection of osteoclast-like giant cell tumor in the left lobe of
      the liver. An 18F-FDG PET/CT scan was performed to evaluate the recurrent tumor.
      The images demonstrated the recurrent malignancy in the liver. In addition,
      metastatic lesions in both the abdomen and the chest were revealed.

PMID- 22955081
TI  - An atypical relapse of acute myeloid leukemia diagnosed by 18F-FDG PET/CT.
AB  - Extramedullary relapse of acute myeloid leukemia (AML) after stem-cell transplant
      is very rare and often remains a diagnostic challenge. Although the diagnostic
      value of PET/CT has not been evaluated thoroughly in leukemia, it might be useful
      for detecting these focal localizations. We presented a case of a 58-year-old
      man, with a prior history of localized bladder cancer and a secondary AML,
      referred to our hospital with important thoracic backaches. PET/CT revealed the
      presence of meningeal carcinomatosis at the thoracic level, as well as lymph
      nodes, and muscular and bone metastases. Immunophenotyping of the cerebrospinal
      fluid aspirate showed a relapse of AML.

PMID- 22955082
TI  - Retroperitoneal Castleman disease on 99mTc DTPA renal scintigraphy.
AB  - We report a case of pathology-proven retroperitoneal Castleman disease, which
      demonstrated elevated 99mTc DTPA accumulation on renal scintigraphy in a 48-year
      old man who presented with back pain.

PMID- 22955083
TI  - Current readings in nuclear medicine.

PMID- 22955084
TI  - (11)C-methionine PET/CT and MRI of primary central nervous system diffuse large B
      cell lymphoma before and after high-dose methotrexate.
AB  - PURPOSE: Although the optimum treatment of primary central nervous system
      lymphoma (PCNSL) remains a challenge, there is increasing interest in
      methotrexate-based chemotherapy as an effective strategy. Here, we report
      evidence supporting the utility of methionine PET/CT for evaluating PCNSL disease
      extent and response to high-dose methotrexate therapy. PATIENTS AND METHODS: Four
      patients newly diagnosed with diffuse large B-cell PCNSL underwent methionine
      PET/CT and MRI of the brain at baseline and again after completion of high-dose
      methotrexate combination chemotherapy. Three patients also received pretreatment
      FDG PET/CT, and the intervals between MRI and both PET/CTs were within 3 weeks.
      The results of methionine PET/CT were compared with MRI and clinical findings.
      RESULTS: Pretreatment methionine PET/CT demonstrated clear demarcation of PCNSL
      tumors with high contrast in 3 patients and only faint uptake in the remaining
      patient, which also showed low FDG uptake. In 1 patient, methionine PET/CT
      displayed more tumor lesions than FDG PET/CT did. After high-dose methotrexate
      chemotherapy, methionine images displayed complete disappearance of abnormal
      uptake in all 4 patients. In 3 of the patients, posttreatment MRI and clinical
      follow-up corroborated findings of complete remission. In the remaining patient,
      MRI showed nonenhancing T2 hyperintensities in the periventricular white matter,
      for which the significance was inconclusive. CONCLUSIONS: Methionine PET/CT may
      provide clinically useful information complementary to MRI for monitoring the
      response to systemic chemotherapy in patients with PCNSL.

PMID- 22955085
TI  - From the editor.

PMID- 22955086
TI  - Evaluating outcomes of care and targeting quality improvement using Medicare
      health outcomes survey data.
AB  - The Medicare Health Outcomes Survey (HOS) provides a rich source of outcomes data
      on the Medicare Advantage (MA) program for the US Department of Health and Human
      Services, managed care organizations participating in Medicare, quality
      improvement organizations, and health services researchers working to improve
      quality of care for Medicare enrollees. Since 1998, the Centers for Medicare and
      Medicaid Services has collected longitudinal functional status information to
      assess the performance of Medicare managed care organizations. This introduction
      reviews the goals of the HOS program, how the HOS supports health care reform,
      and outlines recent HOS studies exploring data applications for monitoring
      outcomes and implementing quality improvement activities.

PMID- 22955087
TI  - Monitoring outcomes for the Medicare Advantage program: methods and application
      of the VR-12 for evaluation of plans.
AB  - The Veterans RAND 12-Item Health Survey (VR-12) is one of the major patient
      reported outcomes for ranking the Medicare Advantage (MA) plans in the Health
      Outcomes Survey (HOS). Approaches for scoring physical and mental health are
      given using contemporary norms and regression estimators. A new metric approach
      for the VR-12 called the "VR-6D" is presented with case-mix adjustments for
      monitoring plans that combine utilities and mortality. Results show that the
      models for ranking health outcomes of the plans are robust and credible. Future
      directions include the use of utilities for evaluating and ranking of MA plans.

PMID- 22955088
TI  - Identifying older adults at high risk of mortality using the Medicare health
      outcomes survey.
AB  - The Vulnerable Elders Survey (VES), a screening tool for at-risk elderly, has
      been validated in the community. This study used VES-based criteria to develop a
      modified version that can be calculated from the Medicare Health Outcomes Survey
      (HOS) to identify Medicare members at high risk of mortality. Data were from
      97,258 HOS respondents in 164 plans. Using age, self-rated health, and function
      items from the 2005 HOS, an a priori approach modeled on VES scoring and items
      predicted two-year mortality (c-statistic 0.74). Routinely-collected Medicare
      survey data may be used to assess patterns of enrollment of high-risk
      beneficiaries across health plans.

PMID- 22955089
TI  - Activities of daily living, chronic medical conditions, and health-related
      quality of life in older adults.
AB  - This study investigated associations between chronic medical conditions,
      activities of daily living (ADL), and health-related quality of life (HRQOL). Our
      findings suggest that the number of ADL limitations reported by older adults is
      associated with their HRQOL. Findings from our analyses also suggest that the
      association between having multiple comorbid conditions and HRQOL is stronger for
      those with no ADL limitations than those with at least some limitations. These
      data will aid practitioners in determining the relative importance of chronic
      medical conditions and ADL limitations on HRQOL and demonstrate how ADL
      limitations and comorbid conditions may differentially impact HRQOL.

PMID- 22955090
TI  - Transformational leadership in medical practice: capturing and influencing
      principles-driven work.
AB  - The importance of leadership in medicine is well recognized. Transformational
      leadership is a well-defined model that provides an empirically supported
      approach to foster organizational and personal change. It has been applied in
      health care settings with favorable outcomes. Transformational leadership is
      intended to help subordinates and followers transcend usual expectations of their
      own capabilities to reach higher levels of performance and personal meaning. The
      application of transformational leadership is appropriate to physicians in many
      roles, including to those who are supervisors in medical education or practice as
      team members in outpatient settings. Illustrations exemplify these points.

PMID- 22955091
TI  - Physician organization-practice team integration for the advancement of patient
      centered care.
AB  - The patient-centered medical home is being promoted as a cornerstone for
      transforming primary care. Physician organizations (POs) are playing a more
      prominent role by facilitating practices' transformation to the patient-centered
      medical home. Using a framework of organizational integration, we investigated
      the changing relationship between POs and practices through qualitative
      interviews. Through increased integration, POs can support both the big picture
      and day-to-day activities of practice transformation. Most PO-practice unit
      connections we identified reflected new areas of engagement-competencies that POs
      were not developing in the past-that are proving integral to the broad-scale
      practice change of patient-centered medical home implementation.

PMID- 22955092
TI  - Challenges and strategies in serving the uninsured in Nashville, Tennessee.
AB  - This study identified challenges faced by a healthcare safety net system. Surveys
      of safety net outpatient clinic and hospital emergency department (ED) facilities
      and key informant interviews ascertained barriers to providing necessary client
      services and strategies to overcome them. About 60% of key informants responded
      that Medicaid cuts greatly increased the numbers of uninsured clients. The
      outpatient clinic and ED personnel reported that the capacity of providers to
      care for these increasing numbers of uninsured was primarily strained by limited
      referral resources for needed specialty care. The most commonly cited successful
      coping strategies for clinics were networking and partnering. [corrected].

PMID- 22955093
TI  - The appropriate uses of bundled or episode of illness classification systems.
AB  - Health care reform's foremost challenge is to reduce overall cost trends.
      Episodes of care are one strategy to promote accountability for cost efficiency
      and quality improvement and are referred to 10 times in the Patient Protection
      and Accountable Care Act. This article outlines the strengths and limitations of
      3 types of episodes for both payment and/or profiling.

PMID- 22955095
TI  - Synthesis and evaluation of indole-containing 3,5-diarylisoxazoles as potential
      pro-apoptotic antitumour agents.
AB  - A series of novel indole-containing diarylisoxazoles has been synthesised, based
      on our previous work on the synthesis and pro-apoptotic antitumour activity of
      indole-based diaryl 1,2,4-oxadiazoles. Concise synthetic routes to both 3-(indol
      2-yl)-5-phenylisoxazoles and 5-(indol-2-yl)-3-phenylisoxazoles have been
      developed with full regiochemical control, bearing substituents on the indole
      ring, indole nitrogen, and/or phenyl group. Additionally a series of the related
      5-(1H-indol-5-yl)-3-phenylisoxazoles has been prepared. In vitro evaluation in
      human cancer cell lines Colo320 (colon) and Calu-3 (lung) revealed preferential
      antiproliferative activity within the 5-(indol-5-yl)-3-phenylisoxazole series
      (low micromolar IC(50)). Further analysis revealed the ability of the indol-5-yl
      series to induce expression of effector caspases-3 and -7, and retention of
      viability of the human bronchial smooth muscle cell (BSMC) control cell
      population (particularly for compounds 18c and 18e).

PMID- 22955096
TI  - Substance misuse and traumatic brain injury. Preface.

PMID- 22955097
TI  - A randomized controlled trial of brief intervention for problem alcohol use in
      persons with traumatic brain injury.
AB  - OBJECTIVE: : To investigate the effectiveness of brief intervention for modifying
      alcohol expectancies, readiness to change, and problem alcohol use in persons
      with traumatic brain injury (TBI). DESIGN: : Randomized controlled trial, with 3
      month follow-up. SETTING: : Three level I Trauma Centers. PARTICIPANTS: : One
      hundred four persons with complicated mild, moderate, or severe TBI, with
      preinjury problem alcohol use, who had emerged from posttraumatic amnesia.
      INTERVENTION: : Twenty- to 30-minute brief intervention (education and
      motivational interview). MAIN MEASURES: : Alcohol Expectancy Questionnaire-III
      Global Positive Expectancies and Cognitive and Physical Impairment scales;
      Readiness to Change Questionnaire; problem alcohol use. RESULTS: : After
      controlling for relevant covariates, there was an effect of treatment on
      expectation that alcohol use would result in cognitive and physical impairment.
      This effect was moderated by injury severity, and was only effective for those
      with severe injury. There was no treatment effect on global positive
      expectancies, readiness to change, or problem alcohol use. Attribution of injury
      to alcohol use was associated with the expectation that alcohol use would result
      in cognitive and physical impairment, and at one center, in greater readiness to
      change. CONCLUSIONS: : Although the brief intervention did not have an impact on
      problem alcohol use, positive alcohol expectancies, or readiness to change, the
      results of this study suggest that brief intervention can be effective for
      educating on the negative impact of alcohol use for people with severe TBI who
      have emerged from posttraumatic amnesia. Attribution of the injury to alcohol use
      could potentially increase readiness to change in some settings, and might be
      used to generate discussion about the negative impact of alcohol use.

PMID- 22955098
TI  - Investigation of the effectiveness of brief interventions to reduce alcohol
      consumption following traumatic brain injury.
AB  - OBJECTIVE: To examine the relative effectiveness of brief interventions
      comprising an information booklet with and without a brief motivational interview
      and an informal discussion in reducing alcohol use following traumatic brain
      injury. PARTICIPANTS: Sample of 60 participants with traumatic brain injury (mean
      age = 35 years) with preinjury history of alcohol use. RESEARCH DESIGN:
      Randomized controlled trial, using block randomization, stratified for gender.
      METHODS AND PROCEDURES: Following collection of demographic information and
      alcohol consumption data using the Time Line Follow-Back, participants were
      randomly allocated to 1 of 3 groups (informal discussion, information only, or
      motivational interview) and given appropriate treatment. Follow-up assessments
      were completed by an independent researcher 6 months later. RESULTS:
      Nonparametric significance testing was used to compare differences in frequency
      and quantity of alcohol consumption at preintervention (6-9 months postinjury)
      and follow-up (12-15 months postinjury) sessions. There was a positive trend
      showing participants in both the intervention groups to be drinking less
      frequently and consuming fewer alcoholic drinks than those in the informal
      discussion (control) group. However, group differences did not reach statistical
      significance. CONCLUSIONS: Further randomized controlled trials with larger
      samples are needed to establish whether brief educational and motivational
      interview interventions targeting alcohol use are efficacious in the traumatic
      brain injury population.

PMID- 22955099
TI  - Who responds better? Factors influencing a positive response to brief alcohol
      interventions for individuals with traumatic brain injury.
AB  - OBJECTIVE: To investigate variables associated with the frequency and quantity of
      alcohol consumption following a brief alcohol intervention in individuals with
      traumatic brain injury. PARTICIPANTS: Initial sample of 60 participants with
      traumatic brain injury (mean age = 35 years) with preinjury history of alcohol
      use; of whom, 50 were evaluated at follow-up. RESEARCH DESIGN: Randomized
      controlled trial, stratified for gender, which used a random-effects regression
      model to examine the association of predictor variables with the frequency and
      quantity of alcohol use 6 months following a brief alcohol intervention. MAIN
      MEASURES: Alcohol Use Disorders Identification Test; Time Line Follow Back;
      California Verbal Learning Test-II; Modified Six Elements Test; Readiness to
      Change Questionnaire; and Hospital Anxiety and Depression Scale. INTERVENTIONS:
      Participants received one of the following treatments: informal discussion;
      discussion plus information; and brief motivational interview plus information.
      RESULTS: While both intervention groups showed less drinking, the intervention
      group membership effect was not significant. Being in the action stage of
      readiness to change was associated with lower drinking frequency and quantity.
      Higher education and higher levels of depression were associated with increased
      drinking. Memory and executive function, and heavy preinjury alcohol use, were
      not significant predictors. CONCLUSIONS: These findings support a focus on
      readiness to change behavior and treatment of depression in addressing alcohol
      use issues following traumatic brain injury. Treatment efficacy studies in larger
      samples are needed.

PMID- 22955100
TI  - Frequent binge drinking after combat-acquired traumatic brain injury among active
      duty military personnel with a past year combat deployment.
AB  - OBJECTIVE: To determine whether combat-acquired traumatic brain injury (TBI) is
      associated with postdeployment frequent binge drinking among a random sample of
      active duty military personnel. PARTICIPANTS: Active duty military personnel who
      returned home within the past year from deployment to a combat theater of
      operations and completed a survey health assessment (N = 7155). METHODS: Cross
      sectional observational study with multivariate analysis of responses to the 2008
      Department of Defense Survey of Health Related Behaviors Among Active Duty
      Military Personnel, an anonymous, random, population-based assessment of the
      armed forces. MAIN MEASURES: Frequent binge drinking: 5 or more drinks on the
      same occasion, at least once per week, in the past 30 days. TBI-AC: self-reported
      altered consciousness only; loss of consciousness (LOC) of less than 1 minute
      (TBI-LOC <1); and LOC of 1 minute or greater (TBI-LOC 1+) after combat injury
      event exposure. RESULTS: Of active duty military personnel who had a past year
      combat deployment, 25.6% were frequent binge drinkers and 13.9% reported
      experiencing a TBI on the deployment, primarily TBI-AC (7.5%). In regression
      models adjusting for demographics and positive screen for posttraumatic stress
      disorder, active duty military personnel with TBI had increased odds of frequent
      binge drinking compared with those with no injury exposure or without TBI: TBI-AC
      (adjusted odds ratio, 1.48; 95% confidence interval, 1.18-1.84); TBI-LOC 1+
      (adjusted odds ratio, 1.67; 95% confidence interval, 1.00-2.79). CONCLUSIONS:
      Traumatic brain injury was significantly associated with past month frequent
      binge drinking after controlling for posttraumatic stress disorder, combat
      exposure, and other covariates.

PMID- 22955102
TI  - Psychiatric diagnoses, mental health utilization, high-risk behaviors, and self
      directed violence among veterans with comorbid history of traumatic brain injury
      and substance use disorders.
AB  - OBJECTIVES: To describe various characteristics of veterans with co-occurring
      histories of traumatic brain injury (TBI) and substance use disorder (SUD) for
      purposes of hypothesis generation. STUDY DESIGN: Archival data collected over a
      period of 4 years. PARTICIPANTS: Sixty-five veterans across eras of service with
      confirmed histories of TBI and SUD. METHODS: : Demographic and TBI information
      were obtained from an archival clinical database. Electronic medical records were
      reviewed for mental health utilization, psychiatric diagnoses, self-directed
      violence, and risk-taking behaviors. RESULTS: In addition to a SUD, veterans were
      reported to have an average of 3 additional psychiatric diagnoses and a median of
      3 TBIs per person. All utilized various mental health services in addition to
      substance use treatment. Individuals were found to have engaged in a variety of
      risky behaviors. There were significant associations between suicidal ideation
      and assaultive behaviors, as well as between suicide attempt and impulsivity.
      CONCLUSIONS: This study describes a sample of veterans with co-occurring
      histories of TBI, SUD, risk-taking behaviors, and self-directed violence. More
      research is needed to examine these complex interrelationships and to identify
      specific risk factors for intervention/prevention strategies.

PMID- 22955101
TI  - The effect of blood alcohol level and preinjury chronic alcohol use on outcome
      from severe traumatic brain injury in Hispanics, anglo-Caucasians, and African
      americans.
AB  - OBJECTIVE: To examine (a) ethnic differences in blood alcohol level (BAL) and
      preinjury chronic alcohol use (PI-ETOH) within a severe closed head injury (CHI)
      sample and (b) the main and interaction effects of BAL, PI-ETOH, and ethnicity on
      functional outcome following severe CHI. PARTICIPANTS: A total of 434 Hispanic,
      Anglo-Caucasian, and African-American individuals with severe CHI. DESIGN:
      Retrospective cohort study. SETTING: Consecutive admissions to a level 1 trauma
      center. MAIN MEASURES: After admission to the trauma center, BAL was collected
      for each patient. Additional information regarding PI-ETOH was collected in a
      subset of patients (N = 116). Functional outcome was measured using the
      Disability Rating Scale (DRS) at 6 months after injury. RESULTS: A one-way
      analysis of variance revealed ethnic differences in mean BAL. Hierarchical
      multiple regression indicated that BAL did not predict DRS outcomes after
      controlling for pertinent covariates. An interaction effect between PI-ETOH and
      ethnicity was observed, such that presence of chronic alcohol use predicted worse
      functional outcome for Anglo-Caucasians and African-Americans, but more favorable
      outcome for Hispanics. CONCLUSIONS: Ethnic differences in BALs within our severe
      traumatic brain injury sample mirrored ethnic drinking patterns observed in the
      general population, with Hispanics having the highest BALs. A paradoxical
      relationship between PI-ETOH and functional outcome was observed for Hispanics.

PMID- 22955103
TI  - Atheroprotective mechanisms of shear stress-regulated microRNAs.
AB  - MicroRNAs (miRs) are small non-coding RNAs that control gene expression by
      inhibiting translation or inducing degradation of targeted mRNA. miRs play a
      crucial role in vascular homeostasis but also during pathophysiological
      processes. Functionally active endothelial cells maintain homeostasis of the
      vasculature and protect against cardiovascular disease. The mechanical activation
      of endothelial cells by laminar shear stress provides a potent atheroprotective
      effect and reduces endothelial inflammation and cell cycle progression. Laminar
      shear stress induces profound changes in gene expression and recently was shown
      to regulate various miRs. The down-regulation of miR-92a by shear stress enhances
      the expression of the endothelial nitric oxide synthase, whereas the up
      regulation of miR-19a contributes to the shear stress-induced inhibition of cell
      proliferation. In addition, members of the miR-23-27-24 cluster are increased and
      specifically miR-23b blocks cell cycle progression, whereas miR-27b was shown to
      reduce endothelial cell repulsive signals. Finally, increased miR-10 expression
      in atheroprotected regions reduced the inflammatory response of endothelial cells
      and increased endothelial miR-143/145 levels improved smooth muscle cells
      functions. Together, the regulation of miRs by shear stress contributes to the
      anti-inflammatory, cell cycle inhibitory and vasculoprotective effects in
      endothelial cells.

PMID- 22955105
TI  - CP12 residues involved in the formation and regulation of the glyceraldehyde-3
      phosphate dehydrogenase-CP12-phosphoribulokinase complex in Chlamydomonas
      reinhardtii.
AB  - CP12, a member of the intrinsically disordered protein family, forms a stable
      complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and
      phosphoribulokinase (PRK). To understand the function of conserved residues of
      CP12 in the formation of the GAPDH-CP12-PRK complex and in the regulation of the
      enzymes within this complex, we have produced mutants of CP12 by site-directed
      mutagenesis. The GAPDH, CP12 and PRK recombinant proteins are able to
      reconstitute spontaneously the ternary complex that has been described in
      Chlamydomonas reinhardtii. Our analysis reveals that the central part
      ((35)WXXVEE(47)) of CP12 is required to form the GAPDH-CP12-PRK complex. Using
      the same series of single amino acid replacements, we have identified individual
      residues, which seem to represent also contact points for GAPDH. Most notably,
      substitution of glutamate 74 prevents the binding of GAPDH to CP12. This is
      similar to the mutant C66S, with which the GAPDH-CP12-PRK complex is not formed.
      In contrast, replacement of the three last residues ((78)YED(80)) of CP12 has no
      effect on the formation of the ternary supra-molecular complex. However, our
      findings strongly suggest that Y78 and D80 are involved in the regulation of the
      GAPDH activity within the supra-molecular complex, since the mutants, D80K and
      Y78S, do not down-regulate the activity of GAPDH. The replacement of the amino
      acid E79 weakens the interaction between GAPDH and CP12 as no GAPDH-CP12 sub
      complex is formed. In this case, nevertheless, the supra-molecular complex is
      formed when PRK is present indicating that PRK strengthens the interaction
      between GAPDH and CP12 within the supra-molecular complex.

PMID- 22955104
TI  - Role of photoperiod on hormone concentrations and adaptive capacity in tree
      shrews, Tupaia belangeri.
AB  - Environmental factors, such as photoperiod and temperature, play an important
      role in the regulation of an animal's physiology and behavior. In the present
      study, we examined the effects of short photoperiod (SD, 8L:16D) on body mass as
      well as on several physiological, hormonal, and biochemical measures indicative
      of thermogenic capacity, to test our hypothesis that short photoperiod stimulates
      increases thermogenic capacity and energy intake in tree shrews. At the end,
      these tree shrews (SD) had a significant higher body mass, energy intake,
      cytochrome C oxidase (COX) activity and uncoupling protein-1 (UCP1) content,
      serum tri-iodothyronine (T(3)) and thyroxine (T(4)) compared to LD (16L:8D) tree
      shrews. However, there were no significant differences in serum leptin and
      melatonin between the two groups. Together, these data suggest tree shrews employ
      a strategy of maximizing body growth and increasing energy intake in response to
      cues associated with short photoperiod.

PMID- 22955106
TI  - Optimisation of liver and intestine in vitro models for pharmacokinetics and
      pharmacodynamics studies. STREP - 037499 (Specific Targeted REsearch or
      innovation Project).

PMID- 22955107
TI  - PIK3CA overexpression is a possible prognostic factor for favorable survival in
      ovarian clear cell carcinoma.
AB  - Dysregulated signaling on the PI3-kinase/Akt cascade is reportedly associated
      with early stage and favorable prognosis in some kinds of malignancies including
      breast cancer, endometrial cancer, and colorectal cancer. PIK3CA, a catalytic
      subunit of PI3-kinase, is known to be activated in ovarian clear cell carcinoma
      (CCC), which is categorized as type I ovarian cancer. The aim of this study was
      to investigate the clinical significance of PIK3CA overexpression in the disease.
      We performed immunohistochemical analyses of PIK3CA, PTEN, p-Akt, p27 and p53
      expressions in primary ovarian clear cell carcinomas from 62 Japanese patients.
      Genetic analyses of PIK3CA mutation and amplification were further conducted.
      PIK3CA was overexpressed in 45 tumors (73%), PTEN expression was negative in 3
      (5%), and p53 was positive in 8 (13%). Overexpressed PIK3CA was found to be
      associated with p-Akt overexpression (P = .007). PIK3CA overexpression tended to
      be observed in more of stage I disease (73% versus 47%, P = .07) and was
      associated with absence of residual tumor at the initial surgery (96% versus 71%,
      P = .01). Furthermore, survival analyses revealed that PIK3CA overexpression
      correlated with improved overall survival (P = .03). Subsequent genetic analyses
      demonstrated that PIK3CA overexpression correlated with the presence of mutation
      or amplification of the PIK3CA gene in tumors (P = .009). Our observations
      suggest that the subgroup of ovarian clear cell carcinomas harboring activated
      PIK3CA seems to have better prognosis possibly due to more indolent biological
      property compared to tumors without PIK3CA activation. PIK3CA may serve as a
      biomarker for good prognosis and a possible therapeutic target in this lethal
      subtype of ovarian cancer.

PMID- 22955108
TI  - Association of mammalian target of rapamycin with aggressive type II endometrial
      carcinomas and poor outcome: a potential target treatment.
AB  - The classification of endometrial carcinoma divided into types I and II has shown
      clinical usefulness. Molecular alterations of PTEN and Wnt/beta-catenin have been
      identified in this neoplasia. However, the role of mammalian target of rapamycin
      according to subcellular localization in the pathogenesis of this neoplasia and
      its prognostic significance are not well defined. We studied the expression of
      phosphorylated mammalian target of rapamycin, PTEN, and beta-catenin and their
      relationship with clinicopathologic features, molecular factors (microsatellite
      instability, mismatch repair, and BRAF genes) and patients' survival in a series
      of 260 nonconsecutive endometrial carcinomas. Tissue microarrays were manually
      constructed, and genomic DNA was extracted from paraffin-embedded cylinders (1 mm
      thick) from preselected tumor areas. The mammalian target of rapamycin in the
      nuclei (mTORC2; 47%) or cytoplasm (mTORC1; 48%) were seen in type II endometrial
      carcinoma, the latter also in advanced stages (P <= .046). PTEN loss (58%) was
      detected in type I endometrial carcinoma of grade 1, at early stage, with
      mismatch repair gene loss (24.4%) and microsatellite instability-positive status
      (22%; P <= .05). Nuclear beta-catenin (16%) was found in type I tumors of younger
      patients (P <= .003). In contrast, BRAF-V600E mutations were not detected (0%).
      Mammalian target of rapamycin cytoplasmic high expression implied poorer
      prognosis (P = .02; Kaplan-Meier, log-rank test), but grade 3 tumors, vascular
      invasion, advanced stage, or PTEN presence correlated independently with a
      negative impact on survival (all P <= .036; Cox analysis). Our results show that
      mammalian target of rapamycin, PTEN, and beta-catenin are independently involved
      in different molecular subtypes of endometrial carcinoma with diverse patients'
      prognosis and support their distinctive treatment based on targeted drugs.

PMID- 22955109
TI  - The role of TGF-beta and myofibroblasts in the arteritis of Kawasaki disease.
AB  - Inflammation of medium-sized, muscular arteries and coronary artery aneurysms are
      hallmarks of Kawasaki disease (KD), an acute, self-limited vasculitis of
      children. We previously reported that genetic variation in transforming growth
      factor (TGF)-beta pathway genes influences both susceptibility to KD and coronary
      artery aneurysm (CAA) formation. TGF-beta signaling has been implicated in the
      generation of myofibroblasts that influence collagen lattice contraction, antigen
      presentation, and recruitment of inflammatory cells as well as the generation of
      regulatory T-cells (Tregs). These processes could be involved in aneurysm
      formation and recovery in KD. Coronary artery tissues from 8 KD patient autopsies
      were stained to detect proteins in the TGF-beta pathway, to characterize
      myofibroblasts, and to detect Tregs. Expression of proteins in the TGF-beta
      pathway was noted in infiltrating mononuclear cells and spindle-shaped cells in
      the thickened intima and adventitia. Coronary arteries from an infant who died on
      Illness Day 12 showed alpha-smooth muscle actin (SMA)-positive, smoothelin
      negative myofibroblasts in the thickened intima that co-expressed IL-17 and IL-6.
      CD8+ T-cells expressing HLA-DR+ (marker of activation and proliferation) were
      detected in the aneurysmal arterial wall. Forkhead box P3 (FOXP3), whose
      expression is essential for Tregs, was also detected in the nucleus of
      infiltrating mononuclear cells, suggesting a role for Tregs in recovery from KD
      arteritis.TGF-beta may contribute to aneurysm formation by promoting the
      generation of myofibroblasts that mediate damage to the arterial wall through
      recruitment of pro-inflammatory cells. This multi-functional growth factor may
      also be involved in the induction of Tregs in KD.

PMID- 22955110
TI  - Incidence and short-term mortality from perforated peptic ulcer in Korea: a
      population-based study.
AB  - BACKGROUND: Perforated peptic ulcer (PPU) is associated with serious health and
      economic outcomes. However, few studies have estimated the incidence and health
      outcomes of PPU using a nationally representative sample in Asia. We estimated
      age- and sex-specific incidence and short-term mortality from PPU among Koreans
      and investigated the risk factors for mortality associated with PPU development.
      METHODS: A retrospective population-based study was conducted from 2006 through
      2007 using the Korean National Health Insurance claims database. A diagnostic
      algorithm was derived and validated to identify PPU patients, and PPU incidence
      rates and 30-day mortality rates were determined. RESULTS: From 2006 through
      2007, the PPU incidence rate per 100 000 population was 4.4; incidence among men
      (7.53) was approximately 6 times that among women (1.24). Incidence significantly
      increased with advanced age, especially among women older than 50 years. Among
      4258 PPU patients, 135 (3.15%) died within 30 days of the PPU event. The 30-day
      mortality rate increased with advanced age and reached almost 20% for patients
      older than 80 years. The 30-day mortality rate was 10% for women and 2% for men.
      Older age, being female, and higher comorbidity were independently associated
      with 30-day mortality rate among PPU patients in Korea. CONCLUSIONS: Special
      attention should be paid to elderly women with high comorbidity who develop PPU.

PMID- 22955111
TI  - Improving the efficiency and relevance of evidence-based recommendations in the
      era of whole-genome sequencing: an EGAPP methods update.
AB  - To provide an update on recent revisions to Evaluation of Genomic Applications in
      Practice and Prevention (EGAPP) methods designed to improve efficiency, and an
      assessment of the implications of whole genome sequencing for evidence-based
      recommendation development. Improvements to the EGAPP approach include automated
      searches for horizon scanning, a quantitative ranking process for topic
      prioritization, and the development of a staged evidence review and evaluation
      process. The staged process entails (i) triaging tests with minimal evidence of
      clinical validity, (ii) using and updating existing reviews, (iii) evaluating
      clinical validity prior to analytic validity or clinical utility, (iv) using
      decision modeling to assess potential clinical utility when direct evidence is
      not available. EGAPP experience to date suggests the following approaches will be
      critical for the development of evidence based recommendations in the whole
      genome sequencing era: (i) use of triage approaches and frameworks to improve
      efficiency, (ii) development of evidence thresholds that consider the value of
      further research, (iii) incorporation of patient preferences, and (iv) engagement
      of diverse stakeholders. The rapid advances in genomics present a significant
      challenge to traditional evidence based medicine, but also an opportunity for
      innovative approaches to recommendation development.

PMID- 22955113
TI  - Laboratory testing of CYP2D6 alleles in relation to tamoxifen therapy.
AB  - Tamoxifen, a widely prescribed drug for the treatment and prevention of breast
      cancer, is metabolized to more potent metabolites by the cytochrome P450 2D6
      (CYP2D6) enzyme. Variants in the CYP2D6 gene can cause patients to be either
      intermediate or poor metabolizers, thereby rendering tamoxifen treatment less
      effective. Testing for CYP2D6 gene variants is available in Clinical Laboratory
      Improvement Amendments-certified clinical laboratories; however, the biological
      complexity of the variants makes result interpretation and phenotype prediction
      challenging. This article describes the clinical significance of variants as well
      as important analytical, interpretative, and reporting issues. It is designed to
      be a guideline for clinical laboratory professionals in performing tests and
      interpreting results with respect to CYP2D6 genetic variants.

PMID- 22955112
TI  - Women's experiences receiving abnormal prenatal chromosomal microarray testing
      results.
AB  - PURPOSE: Genomic microarrays can detect copy-number variants not detectable by
      conventional cytogenetics. This technology is diffusing rapidly into prenatal
      settings even though the clinical implications of many copy-number variants are
      currently unknown. We conducted a qualitative pilot study to explore the
      experiences of women receiving abnormal results from prenatal microarray testing
      performed in a research setting. METHODS: Participants were a subset of women
      participating in a multicenter prospective study "Prenatal Cytogenetic Diagnosis
      by Array-based Copy Number Analysis." Telephone interviews were conducted with 23
      women receiving abnormal prenatal microarray results. RESULTS: We found that five
      key elements dominated the experiences of women who had received abnormal
      prenatal microarray results: an offer too good to pass up, blindsided by the
      results, uncertainty and unquantifiable risks, need for support, and toxic
      knowledge. CONCLUSION: As prenatal microarray testing is increasingly used,
      uncertain findings will be common, resulting in greater need for careful pre- and
      posttest counseling, and more education of and resources for providers so they
      can adequately support the women who are undergoing testing.

PMID- 22955114
TI  - Identification of Th1-responsive leishmanial excretory-secretory antigens
      (LESAs).
AB  - The objective of this study was to evaluate the immunomodulatory role of
      leishmanial excretory-secretory antigens (LESAs) released by in vitro cultured
      protozoan parasite Leishmania donovani promastigotes. A total of seventeen
      excretory-secretory proteins of relative molecular weights 11, 13, 16, 18, 21,
      23, 26, 29, 33, 35, 42, 51, 54, 58, 64, 70 and 80 kDa were identified. The
      proteins were divided into five fractions (F1-F5) along with the whole LESAs,
      these fractions were evaluated for their potential antigenicity to induce
      macrophage effector functions, lymphoproliferation and cytokines production
      capabilities. Two fractions, F1 (11, 13 and 16 kDa) and F3 (26, 29 and 33 kDa),
      were found to be highly immunogenic as they significantly induced NADPH oxidase
      and SOD activities as well as NOx, TNF-alpha, IFN-gamma and IL-12 production in
      stimulated RAW 264.7 macrophages. Further, these antigens also induced
      significant proliferation of human peripheral blood mononuclear cells along with
      increased production of IFN-gamma and IL-12. The results strongly suggest the
      potential role of LESAs in the modulation of macrophage effector functions and
      Th1 immune response that gives a hope to develop potent vaccine for visceral
      leishmaniasis.

PMID- 22955115
TI  - Acaricidal action of destruxins produced by a marine-derived Beauveria felina on
      the bovine tick Rhipicephalus (Boophilus) microplus.
AB  - The increasing resistance of Rhipicephalus (Boophilus) microplus tick to
      commercial insecticides requires alternative methods for the control of this
      cattle plague. The enthomopathogenic fungus Beauveria felina produces destruxins
      in culture media, cyclic depsipeptides which display an array of biological
      activities. The present investigation aimed to evaluate the acaricide action of
      destruxins isolated from B. felina culture media on R. (B.) microplus engorged
      females. B. felina was grown in MF medium under 19 different growth conditions.
      HPLC-PDA analysis of chromatographic fractions obtained from the 19 different
      growth media extracts indicated the presence of destruxins in all lipophylic
      fractions. Such fractions were combined and subjected to separation by HPLC.
      Fractions containing distinct destruxins composition were tested against R. (B.)
      microplus. Two fractions, composed of destruxin Ed(1) and pseudodestruxin B
      and/or pseudodestruxin C (fraction P1) as well as by hydroxyhomodestruxin B
      and/or destruxin D and/or roseotoxin C (fraction P7), displayed 30% and 28.7%
      acaricidal efficacy, respectively. This activity profile in such low
      concentration is adequate to consider destruxins as potential leading compounds
      to be developed for tick biological control.

PMID- 22955116
TI  - Mixed-valence [Fe(I)Fe(II)] hydrogenase active site model complexes stabilized by
      a bidentate carborane bis-phosphine ligand.
AB  - A series of [FeFe]-hydrogenase active site analogues, with the general formula
      [Fe(2)(dt)(CO)(4)(BC)] 1-3 (dt = dithiolate, pdt = propyl-1,3-dt (1), bdt =
      benzene-1,2-dt (2), edt = ethyl-1,2-dt (3); BC = 1,2-bisdiphenylphosphine-1,2-o
      carborane), has been prepared and structurally characterized. While the
      electrochemical reductions of 1-3 are largely invariant to the different nature
      of their dt bridges, the oxidations differ by more than 120 mV in between the
      series. Remarkably, all three compounds are reversibly oxidized, with complex 1
      that contains the most electron-donating pdt ligand at the mildest potential of 
      0.09 V vs. Fc/Fc(+). The one-electron oxidized state 1(ox) is stable for several
      minutes and was spectroscopically characterized by FTIR and EPR. EPR spectroscopy
      provided evidence that in the mixed-valence [Fe(I)Fe(II)] state most of the spin
      density is located on the iron with the BC-ligand. This is monitored through the
      strong (31)P hyperfine coupling of the phenyl groups of the BC ligand, while
      further delocalization into the o-carborane unit is negligible.

PMID- 22955117
TI  - Micromotors with built-in compasses.
AB  - We demonstrate here that iron containing rolled-up microtubular engines can be
      magnetized and act as compass needles - they sense the direction of an external
      magnetic field from afar and align the directionalities of their movements
      according to the external field, in a similar fashion to magnetotactic bacteria.

PMID- 22955118
TI  - What is a rust ring?

PMID- 22955119
TI  - Stability of serum eye drops after storage of 6 months.
AB  - PURPOSE: Serum eye drops are used for the treatment of ocular surface disease
      (eg, Sicca syndrome). The objective of this experimental study was to investigate
      whether they maintain their wound-healing potency after a prolonged storage of 6
      months at -20  degrees C and to find a parameter that can serve as a quality and
      stability indicator. METHODS: After obtaining whole blood from 10 volunteers and
      preparing 100% (AS100), 50% (AS50), and 20% (AS20) serum eye drops,
      epitheliotrophic factors including EGF, fibronectin, vitamins A and E, albumin,
      and immunoglobulin A were quantified before and after storage for 7 days at 6 
      degrees C or 3 and 6 months at -20  degrees C. Human corneal epithelial (HCE)
      cell lines were used to investigate proliferation, migration, and overall wound
      healing potency of the cells in response to different serum preparations. The
      proliferation, migration, and wound healing of HCE cells were measured after
      incubation with different serum eye drop concentrations and after different
      storage conditions. RESULTS: The concentration of epidermal growth factor,
      fibronectin, vitamins A and E, immunoglobulin A, and albumin showed no
      significant reduction over the test period. Proliferation, migration, and wound
      healing of HCE cells was significantly better after incubation with undiluted
      serum in comparison with diluted serum. No significant loss of cytokine
      concentration, wound healing, and proliferation effect in HCE culture of AS100,
      AS50, and AS20 could be detected over the 6 months of storage. CONCLUSIONS: The
      concentration of a spectrum of cytokines involved in corneal epithelial wound
      healing and the epitheliothrophic effect of serum are not significantly changed
      after a prolonged storage of 6 months at -20  degrees C. Hence, it seems
      justifiable to provide patients with appropriate freezer capacity with a 6-month
      supply of autologous serum eye drops. Albumin--which is known to be relevant for
      ocular surface health--could serve as a cost-effective parameter for stability
      controls.

PMID- 22955120
TI  - Efficacy of standardized and quality-controlled cord blood serum eye drop therapy
      in the healing of severe corneal epithelial damage in dry eye.
AB  - PURPOSE: We standardized quality-controlled cord blood serum (CBS)-based eye
      drops and evaluated the efficacy of 1-month CBS treatment in the healing of
      diseased corneal epithelium in severe dry eye (DE) patients. METHODS: Seventeen
      graft-versus-host disease (GVHD) and 13 Sjogren syndrome patients with severe
      persistent corneal defects were enrolled in the framework of a registered
      clinical trial (ClinicalTrials.gov NCT01234623). Sterile CBS eye drops were
      prepared to supply 0.15 ng per eye per day epithelial growth factor and
      administered for 1 month in a 1-day dose dispensing. The extent of epithelial
      defect was evaluated in square millimeters area, and subjective symptom score
      (Ocular Surface Disease Index score), Schirmer test I, break-up time, tear
      osmolarity, corneal esthesiometry (Cochet-Bonnet esthesiometer), conjunctival
      scraping, and imprint cytology with goblet cell count were performed at baseline
      (V0) and after 15 (V1) and 30 (V2, endpoint) days of treatment. Satisfaction and
      tolerability questionnaires were evaluated at V1 and V2. RESULTS: A significant
      reduction was shown at the endpoint versus baseline in corneal epithelial damage
      (mean +/- SD, 16.1 +/- 13.7 vs. 40.9 +/- 30 mm2/area, respectively), discomfort
      symptoms (Ocular Surface Disease Index score, 22.3 +/- 10.3 vs. 39.3 +/- 16.9),
      scraping cytology score (3.8 +/- 1.2 vs. 6.6 +/- 2.1), and tear osmolarity (312.5
      +/- 7 vs. 322 +/- 9.1 mOsm/L), whereas a significant improvement was shown in
      corneal esthesiometry (48.2 +/- 2.1 vs. 49.7 +/- 2.1 nylon/mm/length, P < 0.05).
      All patients reported a high degree of satisfaction upon drop instillation.
      CONCLUSIONS: Heterologous CBS-based eye drops represent a promising therapeutic
      approach in the healing of severely injured corneal epithelium and in subjective
      symptom relief. These drops can be obtained as readily available and quality
      controlled blood derivative from cord blood banks on a routine basis.

PMID- 22955121
TI  - Bacterial adhesion forces to Ag-impregnated contact lens cases and transmission
      to contact lenses.
AB  - PURPOSE: To measure adhesion forces of Pseudomonas aeruginosa, Staphylococcus
      aureus, and Serratia marcescens to a rigid contact lens (CL), standard
      polypropylene, and Ag-impregnated lens cases using atomic force microscopy and
      determine bacterial transmission from lens case to CL. METHODS: Adhesion forces
      of bacterial strains to Ag-impregnated and polypropylene lens cases and a rigid
      CL were measured using atomic force microscopy. Adhesion forces were used to
      calculate Weibull distributions, from which transmission probabilities from lens
      case to CL were derived. Transmission probabilities were compared with actual
      transmission of viable bacteria from a lens case to the CL in 0.9% NaCl and in an
      antimicrobial lens care solution. RESULTS: Bacterial transmission probabilities
      from polypropylene lens cases based on force analysis coincided well for all
      strains with actual transmission in 0.9% NaCl. Bacterial adhesion forces on Ag
      impregnated lens cases were much smaller than that on polypropylene and CLs,
      yielding a high probability of transmission. Comparison with actual bacterial
      transmission indicated bacterial killing due to Ag ions during colony-forming
      unit transmission from an Ag-impregnated lens case, especially for P. aeruginosa.
      Transmission of viable bacteria from Ag-impregnated lens cases could be further
      decreased by use of an antimicrobial lens care solution instead of 0.9% NaCl.
      CONCLUSIONS: Bacterial transmission probabilities are higher from Ag-impregnated
      lens cases than from polypropylene lens cases because of small adhesion forces,
      but this is compensated for by enhanced bacterial killing due to Ag impregnation,
      especially when in combination with an antimicrobial lens care solution. This
      calls for a balanced combination of antimicrobial lens care solutions and surface
      properties of a lens case and CL.

PMID- 22955122
TI  - Reply. Phakic descemet stripping automated endothelial keratoplasty: prevalence
      and prognostic impact of postoperative cataracts.

PMID- 22955123
TI  - Subconjunctival bevacizumab injection in pterygium surgery.

PMID- 22955124
TI  - Neurodegenerative causes of death among retired National Football League players.
AB  - OBJECTIVE: To analyze neurodegenerative causes of death, specifically Alzheimer
      disease (AD), Parkinson disease, and amyotrophic lateral sclerosis (ALS), among a
      cohort of professional football players. METHODS: This was a cohort mortality
      study of 3,439 National Football League players with at least 5 pension-credited
      playing seasons from 1959 to 1988. Vital status was ascertained through 2007. For
      analysis purposes, players were placed into 2 strata based on characteristics of
      position played: nonspeed players (linemen) and speed players (all other
      positions except punter/kicker). External comparisons with the US population used
      standardized mortality ratios (SMRs); internal comparisons between speed and
      nonspeed player positions used standardized rate ratios (SRRs). RESULTS: Overall
      player mortality compared with that of the US population was reduced (SMR 0.53,
      95% confidence interval [CI] 0.48-0.59). Neurodegenerative mortality was
      increased using both underlying cause of death rate files (SMR 2.83, 95% CI 1.36
      5.21) and multiple cause of death (MCOD) rate files (SMR 3.26, 95% CI 1.90-5.22).
      Of the neurodegenerative causes, results were elevated (using MCOD rates) for
      both ALS (SMR 4.31, 95% CI 1.73-8.87) and AD (SMR 3.86, 95% CI 1.55-7.95). In
      internal analysis (using MCOD rates), higher neurodegenerative mortality was
      observed among players in speed positions compared with players in nonspeed
      positions (SRR 3.29, 95% CI 0.92-11.7). CONCLUSIONS: The neurodegenerative
      mortality of this cohort is 3 times higher than that of the general US
      population; that for 2 of the major neurodegenerative subcategories, AD and ALS,
      is 4 times higher. These results are consistent with recent studies that suggest
      an increased risk of neurodegenerative disease among football players.

PMID- 22955125
TI  - Ginkgo biloba does not improve cognitive function in MS: a randomized placebo
      controlled trial.
AB  - OBJECTIVE: To determine whether Ginkgo biloba extract (ginkgo) improves cognitive
      function in persons with multiple sclerosis (MS). METHODS: Persons with MS from
      the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or
      more below the mean on one of 4 neuropsychological tests (Stroop Test, California
      Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT],
      and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to
      receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co,
      Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome,
      we compared the performance of the 2 groups on the 4 tests at exit after
      adjusting for baseline performance. RESULTS: Fifty-nine subjects received placebo
      and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo
      were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction
      and severe depression) believed to be unrelated to the treatment occurred in the
      ginkgo group; otherwise, there were no significant differences in AEs. The
      differences (ginkgo - placebo) at exit in the z scores for the cognitive tests
      were as follows: PASAT -0.2 (95% confidence interval [CI] -0.5 to 0.1); Stroop
      Test -0.5 (95% CI -0.9 to -0.1); COWAT 0.0 (95% CI -0.2 to 0.3); and CVLT-II 0.0
      (95% CI -0.3 to 0.3); none was statistically significant. CONCLUSIONS: Treatment
      with ginkgo 120 mg twice a day did not improve cognitive performance in persons
      with MS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that
      treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive
      performance in people with MS.

PMID- 22955126
TI  - Large-scale neuronal network dysfunction in relapsing-remitting multiple
      sclerosis.
AB  - OBJECTIVES: Given that multiple sclerosis (MS) hits diffusely the brain
      hemispheres, we hypothesized that this should result in a distributed pattern of
      functional connectivity (FC) abnormalities. To this aim, we assessed, using
      resting-state (RS) fMRI, intrinsic FC and functional network connectivity (FNC)
      of brain large-scale neuronal networks from 85 patients with relapsing-remitting
      MS (RRMS) and 40 matched controls. METHODS: Independent component analysis was
      used to analyze RS fMRI data. Intrinsic FC of each cluster of each RS network
      (RSN) was compared between controls and patients (analysis of variance adjusted
      for age, gender, and gray matter volume). The FNC toolbox was used to assess
      interactions among RSNs. RESULTS: Compared to controls, patients with RRMS
      experienced a decreased RS FC in regions of the salience (SN), executive control
      (ECN), working memory (WMN), default mode (DMN), sensorimotor, and visual
      networks. They also had an increased RS FC in regions of the ECN and auditory
      RSN. Decreased RS FC was significantly correlated with disability and T2 lesion
      volumes. In patients with RRMS, when compared to controls, FNC analysis showed
      that the ECN had an increased connectivity with the SN and a decreased
      connectivity with the DMN. An abnormal connectivity between the WMNs and sensory
      networks was also found. CONCLUSIONS: Functional abnormalities within and between
      large-scale neuronal networks occur in patients with RRMS and are related to the
      extent of T2 lesions and the severity of disability. Longitudinal studies should
      ascertain whether such functional abnormalities confer a systematic vulnerability
      to disease progression or, conversely, protect against the onset of clinical
      deficits.

PMID- 22955127
TI  - Female risk factors for subarachnoid hemorrhage: a systematic review.
AB  - OBJECTIVE: To systematically review the literature on female risk factors and
      risk of SAH. METHODS: We searched Medline and EMBASE for articles published
      between January 1985 and July 2011. For all studies fulfilling the predefined
      criteria, we obtained risk ratios (RRs) or odds ratios (ORs) with 95% confidence
      intervals (CIs) for female risk factors. We pooled crude and adjusted ORs (aORs)
      with a general variance-based random-effects method. We evaluated methodologic
      quality with the Newcastle-Ottawa Scale. RESULTS: We included 16 studies; 8 had
      good quality. Twelve studies had a case-control design, 3 studies had a
      longitudinal design, and 1 study had a case-crossover design. Overall aORs were
      1.31 (95% CI 1.05-1.64; 5 studies, 2 with good quality [GQ]) for current use of
      combined oral contraceptives (COC), 0.90 (95% CI 0.74-1.09; 7 studies, 4 GQ) for
      ever COC use, 0.86 (95% CI 0.69-1.08; 6 studies, 3 GQ) for current use of hormone
      replacement therapy (HRT), 0.74 (95% CI 0.54-1.00; 3 studies, 1 GQ) for ever use
      of HRT, and 1.29 (95% CI 1.03-1.61; 5 studies, 2 GQ) for postmenopausal women.
      Data on parity and age at menarche were heterogeneous. Risk of subarachnoid
      hemorrhage (SAH) was not increased during pregnancy, labor, or puerperium (RR
      0.40, 95% CI 0.20-0.90; 1 GQ study). CONCLUSIONS: Female hormone levels might
      influence risk of SAH, but the pathophysiology of this effect and its influence
      on the difference in incidence of SAH between the sexes remains unclear. Further
      studies are needed to identify modifiable risk factors of SAH in women older than
      age 50.

PMID- 22955128
TI  - Poststroke fatigue following minor infarcts: a prospective study.
AB  - OBJECTIVE: To explore the potential relationship between fatigue following
      strokes and poststroke mood, cognitive dysfunction, disability, and infarct site
      and to determine the predictive factors in the development of poststroke fatigue
      (PSF) following minor infarcts. METHODS: Ninety-nine functionally active patients
      aged less than 70 years with a first, nondisabling stroke (NIH Stroke Scale score
      <=6 in acute phase and <=3 after 6 months, modified Rankin Scale score <=1 at 6
      months) were assessed during the acute phase and then at 6 (T1) and 12 months
      (T2) after their stroke. Scores in the Fatigue Assessment Inventory were
      described and correlated to age, gender, neurologic and functional impairment,
      lesion site, mood scores, neuropsychological data, laboratory data, and quality
      of life at T1 and T2 using a multivariate logistic regression analysis in order
      to determine which variables recorded at T1 best predicted fatigue at T2. RESULT:
      As many as 30.5% of the patients at T1 and 34.7% at T2 (11.6% new cases between
      T1 and T2) reported fatigue. At both 6 and 12 months, there was a significant
      association between fatigue and a reduction in professional activity. Attentional
      executive impairment, depression, and anxiety levels remained associated with PSF
      throughout this time period, underlining the critical role of these variables in
      the genesis of PSF. There was no significant association between the lesion site
      and PSF. CONCLUSION: This study suggests that attentional and executive
      impairment, as well as depression and anxiety, may play a critical role in the
      development of PSF.

PMID- 22955129
TI  - One step closer to understanding poststroke fatigue.

PMID- 22955130
TI  - Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly
      diagnosed epilepsy in Singapore.
AB  - OBJECTIVE: Asians who carry the HLA-B*1502 allele have an elevated risk of
      developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      when treated with the antiepileptic drugs (AEDs) carbamazepine (CBZ) and
      phenytoin (PHT). With a focus on Singapore, this analysis identifies
      circumstances in which genotyping and targeted treatment with alternative AEDs
      that do not induce SJS/TEN is likely to be more cost-effective than 1) treatment
      with CBZ or PHT without genotyping or 2) providing a more expensive drug that
      does not induce SJS/TEN to all patients without genotyping. METHODS: A decision
      tree model was developed in TreeAge. The model takes into account costs of
      epilepsy treatments and genotyping, reductions in quality of life and increased
      costs resulting from SJS/TEN complications, the prevalence of the risk allele,
      the positive predictive value (PPV) of genotyping, life expectancy, and other
      factors. RESULTS: Compared with no genotyping and providing CBZ to all,
      genotyping results in an incremental cost-effectiveness ratio of $37,030/quality
      adjusted life year (QALY) for Chinese patients, $7,930/QALY for Malays, and
      $136,630/QALY for Indians in Singapore. CONCLUSIONS: Because of the different
      population allele frequencies of HLA-B*1502 among different ethnic groups,
      genotyping for HLA-B*1502 and providing alternate AEDs to those who test positive
      is cost-effective for Singaporean Chinese and Malays, but not for Singaporean
      Indians. Population frequency of HLA-B*1502, PPV, duration of treatment relative
      to life expectancy, and costs of alternative drugs are the key drivers
      influencing cost-effectiveness.

PMID- 22955131
TI  - Silent ischemic lesions in young adults with first stroke are associated with
      recurrent stroke.
AB  - OBJECTIVE: To determine the association between silent ischemic lesions (SILs) on
      baseline brain MRI and recurrent stroke in young adults with first-ever ischemic
      stroke. METHODS: This was a single-center retrospective study of adult patients
      aged 18-50 years with first-ever ischemic stroke investigated by brain MRI
      between 2002 and 2009. Silent brain infarcts (SBIs) were defined as focal T2
      hyperintensities >= 3 mm without corresponding focal symptoms, and leukoaraiosis
      was defined as focal, multifocal, or confluent hyperintensities on T2-weighted
      sequences. The primary outcome was recurrent stroke. A forward stepwise Cox
      regression model was used to determine whether SILs were independently associated
      with recurrent stroke. RESULTS: A total of 271 eligible patients were identified
      in the database: 89 did not undergo MRI imaging and 12 patients had inadequate
      follow-up, leaving a study population of 170 patients. MRI demonstrated SILs in
      48 of 170 (28.2) patients. No patients had isolated leukoaraiosis. Hypertension
      (p = 0.049), migraine with aura (p = 0.02), and cardiovascular disease (p = 0.04)
      were associated with SIL. Mean follow-up duration was 25 +/- 7 months. Among
      patients with SILs, 11 of 48 (23%) had a recurrent stroke vs 8 of 122 (6.5%)
      patients without SIL (p = 0.003). After multivariate Cox regression, SILs
      remained independently associated with recurrent stroke (hazard ratio [HR] 3.2,
      95% confidence interval [CI] 1.2-8.6, p = 0.02), as did the combination of SBIs
      and leukoaraiosis (HR 7.3, 95% CI 2.3-22.9, p = 0.003). CONCLUSIONS: In adults <=
      50 years old with first-ever ischemic stroke, SILs are common and independently
      predict recurrent stroke.

PMID- 22955132
TI  - Large-scale neuronal network dysfunction in multiple sclerosis?: Evidence from
      resting-state fMRI.

PMID- 22955133
TI  - Outcomes from a US military neurology and traumatic brain injury telemedicine
      program.
AB  - OBJECTIVE: This study evaluated usage of the Army Knowledge Online (AKO)
      Telemedicine Consultation Program for neurology and traumatic brain injury (TBI)
      cases in remote overseas areas with limited access to subspecialists. We
      performed a descriptive analysis of quantity of consults, response times, sites
      where consults originated, military branches that benefitted, anatomic locations
      of problems, and diagnoses. METHODS: This was a retrospective analysis that
      searched electronic databases for neurology consults from October 2006 to
      December 2010 and TBI consults from March 2008 to December 2010. RESULTS: A total
      of 508 consults were received for neurology, and 131 consults involved TBI. For
      the most part, quantity of consults increased over the years. Meanwhile, response
      times decreased, with a mean response time of 8 hours, 14 minutes for neurology
      consults and 2 hours, 44 minutes for TBI consults. Most neurology consults
      originated in Iraq (67.59%) followed by Afghanistan (16.84%), whereas TBI
      consults mainly originated from Afghanistan (40.87%) followed by Iraq (33.91%).
      The most common consultant diagnoses were headaches, including migraines (52.1%),
      for neurology cases and mild TBI/concussion (52.3%) for TBI cases. In the
      majority of cases, consultants recommended in-theater management. After receipt
      of consultant's recommendation, 84 known neurology evacuations were facilitated,
      and 3 known neurology evacuations were prevented. CONCLUSIONS: E-mail-based
      neurology and TBI subspecialty teleconsultation is a viable method for overseas
      providers in remote locations to receive expert recommendations for a range of
      neurologic conditions. These recommendations can facilitate medically necessary
      patient evacuations or prevent evacuations for which on-site care is preferable.

PMID- 22955134
TI  - Raeder syndrome produced by extension of chronic inflammation to the internal
      carotid artery.

PMID- 22955135
TI  - Spontaneous intracranial hypotension as an incidental finding on MRI.

PMID- 22955136
TI  - Efficacy of antiepileptic drugs in adults predicts efficacy in children: a
      systematic review.
AB  - OBJECTIVE: Due to the challenges inherent in performing clinical trials in
      children, a systematic review of published clinical trials was performed to
      determine whether the efficacy of antiepileptic drugs (AEDs) in adults can be
      used to predict the efficacy of AEDs in the pediatric population. METHODS:
      Medline/PubMed, EMBASE, and Cochrane library searches (1970-January 2010) were
      conducted for clinical trials of partial-onset seizures (POS) and primary
      generalized tonic-clonic seizures (PGTCS) in adults and in children <2 and 2-18
      years. Independent epidemiologists used standardized search and study evaluation
      criteria to select eligible trials. Forest plots were used to investigate the
      relative strength of placebo-subtracted effect measures. RESULTS: Among 30
      adjunctive therapy POS trials in adults and children (2-18 years) that met
      evaluation criteria, effect measures were consistent between adults and children
      for gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate.
      Placebo-subtracted median percent seizure reduction between baseline and
      treatment periods (ranging from 7.0% to 58.6% in adults and from 10.5% to 31.2%
      in children) was significant for 40/46 and 6/6 of the treatment groups studied.
      The >=50% responder rate (ranging from 2.0% to 43.0% in adults and from 3.0% to
      26.0% in children) was significant for 37/43 and 5/8 treatment groups. In
      children <2 years, an insufficient number of trials were eligible for analysis.
      CONCLUSIONS: This systematic review supports the extrapolation of efficacy
      results in adults to predict a similar adjunctive treatment response in 2- to 18
      year-old children with POS.

PMID- 22955137
TI  - Efficacy of antiepileptic drugs in adults vs children: does one size fit all?

PMID- 22955138
TI  - Age- and sex-specific rates of leukoaraiosis in TIA and stroke patients:
      population-based study.
AB  - OBJECTIVE: To determine any sex differences in age-specific prevalence or
      severity of leukoaraiosis, a marker of white matter ischemia, in population-based
      and clinic cohorts of TIA/stroke and in a systematic review of the literature.
      METHODS: Age-specific sex differences were calculated for both CT and MRI in the
      Oxford Vascular Study (OXVASC) and in an MRI-based clinic cohort. We pooled odds
      ratios (ORs) for leukoaraiosis in women vs men from published studies by fixed
      effect meta-analysis, stratified by patient characteristics (stroke vs nonstroke)
      and CT vs MRI. RESULTS: Among 10 stroke studies (all CT-based), leukoaraiosis was
      most frequent in women (OR = 1.42, 95% confidence interval [CI] 1.27-1.57, p <
      0.0001), with little heterogeneity between studies (p = 0.28). However, no such
      excess was seen in 10 reports of nonstroke cohorts (0.91, 0.67-1.24, p = 0.56).
      Moreover, excess leukoaraiosis in women on CT-imaging in OXVASC (1.38, 1.15-1.67,
      p = 0.001) was explained by their older age (age-adjusted OR = 1.01, 0.82-1.25, p
      = 0.90). Leukoaraiosis was more severe in older (>= 75) women (CT-1.50, 1.14
      1.97, p = 0.004 in OXVASC; MRI-1.70, 1.17-2.48, p = 0.006 in OXVASC and clinic
      cohort). However, leukoaraiosis was independently associated with early mortality
      (hazard ratio = 1.46, 1.23-1.73, p < 0.0001), suggesting that comparisons in
      older age groups will be biased by prior premature death of men with
      leukoaraiosis. Sex differences in severity of leukoaraiosis were not addressed in
      previous studies. CONCLUSIONS: Previously reported excess leukoaraiosis in women
      with TIA/stroke is likely to be confounded by age and apparently greater severity
      in older women is likely to be biased by premature death in men with
      leukoaraiosis.

PMID- 22955139
TI  - Dynamic landscape of tandem 3' UTRs during zebrafish development.
AB  - Tandem 3' untranslated regions (UTRs), produced by alternative polyadenylation
      (APA) in the terminal exon of a gene, could have critical roles in regulating
      gene networks. Here we profiled tandem poly(A) events on a genome-wide scale
      during the embryonic development of zebrafish (Danio rerio) using a recently
      developed SAPAS method. We showed that 43% of the expressed protein-coding genes
      have tandem 3' UTRs. The average 3' UTR length follows a V-shaped dynamic pattern
      during early embryogenesis, in which the 3' UTRs are first shortened at zygotic
      genome activation, and then quickly lengthened during gastrulation. Over 4000
      genes are found to switch tandem APA sites, and the distinct functional roles of
      these genes are indicated by Gene Ontology analysis. Three families of cis
      elements, including miR-430 seed, U-rich element, and canonical poly(A) signal,
      are enriched in 3' UTR-shortened/lengthened genes in a stage-specific manner,
      suggesting temporal regulation coordinated by APA and trans-acting factors. Our
      results highlight the regulatory role of tandem 3' UTR control in early
      embryogenesis and suggest that APA may represent a new epigenetic paradigm of
      physiological regulations.

PMID- 22955141
TI  - Blocking estradiol synthesis affects memory for songs in auditory forebrain of
      male zebra finches.
AB  - Estradiol (E2) has recently been shown to modulate sensory processing in an
      auditory area of the songbird forebrain, the caudomedial nidopallium (NCM). When
      a bird hears conspecific song, E2 increases locally in NCM, where neurons express
      both the aromatase enzyme that synthesizes E2 from precursors and estrogen
      receptors. Auditory responses in NCM show a form of neuronal memory: repeated
      playback of the unique learned vocalizations of conspecific individuals induces
      long-lasting stimulus-specific adaptation of neural responses to each
      vocalization. To test the role of E2 in this auditory memory, we treated adult
      male zebra finches (n=16) with either the aromatase inhibitor fadrozole (FAD) or
      saline for 8 days. We then exposed them to 'training' songs and, 6 h later,
      recorded multiunit auditory responses with an array of 16 microelectrodes in NCM.
      Adaptation rates (a measure of stimulus-specific adaptation) to playbacks of
      training and novel songs were computed, using established methods, to provide a
      measure of neuronal memory. Recordings from the FAD-treated birds showed a
      significantly reduced memory for the training songs compared with saline-treated
      controls, whereas auditory processing for novel songs did not differ between
      treatment groups. In addition, FAD did not change the response bias in favor of
      conspecific over heterospecific song stimuli. Our results show that E2 depletion
      affects the neuronal memory for vocalizations in songbird NCM, and suggest that
      E2 plays a necessary role in auditory processing and memory for communication
      signals.

PMID- 22955142
TI  - Current direction specificity of continuous theta-burst stimulation in modulating
      human motor cortex excitability when applied to somatosensory cortex.
AB  - The present study examines the influence of primary somatosensory cortex (SI) on
      corticospinal excitability within primary motor cortex (M1) using repetitive
      transcranial magnetic stimulation. Two groups of subjects participated and both
      received continuous theta-burst stimulation (cTBS) over SI. One group received
      cTBS oriented to induce anterior-to-posterior (AP) followed by posterior-to
      anterior (PA) current flow in the cortex and the other group received cTBS in the
      opposite direction (PA-AP). Motor evoked potentials (MEPs) were measured from the
      first dorsal interosseous muscle of the left and right hand before and at three
      time points (5, 25, 45 min) following cTBS over left-hemisphere SI. CTBS over SI
      in the AP-PA direction increased contralateral MEPs at 5 and 45 min with a near
      significant increase at 25 min. In contrast, PA-AP cTBS decreased contralateral
      MEPs at 25 min. We conclude that cTBS over SI modulates neural output directed to
      the hand with effects that depend on the direction of induced current.

PMID- 22955140
TI  - Natural genetic variation in yeast longevity.
AB  - The genetics of aging in the yeast Saccharomyces cerevisiae has involved the
      manipulation of individual genes in laboratory strains. We have instituted a
      quantitative genetic analysis of the yeast replicative lifespan by sampling the
      natural genetic variation in a wild yeast isolate. Haploid segregants from a
      cross between a common laboratory strain (S288c) and a clinically derived strain
      (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048
      molecular markers across the genome. Five significant, replicative lifespan QTL
      were identified. Among them, QTL 1 on chromosome IV has the largest effect and
      contains SIR2, whose product differs by five amino acids in the parental strains.
      Reciprocal gene swap experiments showed that this gene is responsible for the
      majority of the effect of this QTL on lifespan. The QTL with the second-largest
      effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying
      genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of
      the rDNA clusters of the parental strains indicated that they play a predominant
      role in the effect of this QTL on longevity. This effect does not appear to
      simply be a function of extrachromosomal ribosomal DNA circle production. The
      results support an interaction between SIR2 and the rDNA locus, which does not
      completely explain the effect of these loci on longevity. This study provides a
      glimpse of the complex genetic architecture of replicative lifespan in yeast and
      of the potential role of genetic variation hitherto unsampled in the laboratory.

PMID- 22955143
TI  - Exploring anterograde associative memory in London taxi drivers.
AB  - London taxi drivers are renowned for their navigation ability, spending a number
      of years acquiring 'The Knowledge' of London's complex layout and having to pass
      stringent examinations to obtain an operating licence. In several studies, this
      navigation skill has been associated with increased posterior but also decreased
      anterior hippocampal grey matter volume. Neuropsychologically, gain and loss has
      also been documented in taxi drivers; while very skilled at navigation in London,
      they are significantly poorer than controls at learning and recalling new object
      location associations. Here we tested a group of London taxi drivers and matched
      control participants on this object-location associations task, while also
      subjecting them to a battery of challenging anterograde associative memory tests
      involving verbal, visual and auditory material both within and across modalities.
      Our aim was to assess whether their difficulty in previous studies reflected a
      general problem with associative memory, or was restricted to the spatial domain.
      We replicated previous findings of poor learning and memory of object-location
      associations. By contrast, their performance on the other anterograde associative
      memory tasks was comparable with controls. This resolves an outstanding question
      in the memory profile of London taxi drivers following hippocampal plasticity,
      and underlines the close relationship between space and the hippocampus.

PMID- 22955144
TI  - Geometric illusions in astronauts during long-duration spaceflight.
AB  - In our previous studies, we have shown that the occurrence of geometric illusions
      was reduced in vestibular patients who presented signs of otolith disorders and
      when healthy observers were tilted relative to gravity. We hypothesized that the
      alteration in the gravitational (otolith) input was responsible for this change,
      presumably because of a connection between vestibular and visual-spatial
      cognitive functions. In this study, we repeated similar experiments in astronauts
      during long-duration spaceflight. In agreement with the data of otolithic
      patients, the inverted-T geometric illusion was less present in the astronauts in
      0 g than in 1g. In addition, the vertical length of drawings made by astronauts
      in orbit was shorter than that on the ground. This result is also comparable with
      the otolithic patients who perceived the vertical length of line drawings to be
      smaller than healthy individuals. We conclude that the impairment in the
      processing of gravitational input in long-duration astronauts affects their
      mental representation of the vertical dimension similar to the otolithic
      patients. The astronauts, however, recover to baseline levels within 1 week after
      returning to Earth.

PMID- 22955145
TI  - Increased local synchronization of resting-state fMRI signal after episodic
      memory encoding reflects off-line memory consolidation.
AB  - The changes of spontaneous activity from before and after a memory or learning
      task had been considered to be related to off-line memory consolidation process
      in human brain by using resting-state functional connectivity (RSFC) MRI (fMRI).
      However, RSFC reflects temporal synchronization of timecourses of spatially
      distinct brain regions and therefore could not determine which specific brain
      region is involved in the memory consolidation process. Here we used regional
      homogeneity (ReHo), a method for measuring local synchronization, to link the
      local spontaneous activity change to off-line episodic memory consolidation. We
      hypothesized that the spontaneous activity change would be different between
      people with better memory performance and those with worse performance in memory
      related regions. All participants completed two resting-state sessions, that is,
      before (REST-1) and after (REST-2) an episodic memory encoding task (picture
      indoor or outdoor judgment). Then, based on the d' of a later surprise memory
      retrieval test, a high-performance group and a low-performance group, each
      consisting of 16 participants, were chosen from whole 58 participants. We defined
      a ReHo ratio, that is, ReHo of REST-2 divided by ReHo of REST-1, as a change
      induced by memory consolidation. The high-performance group showed a significant
      higher ReHo ratio than low-performance group in medial temporal lobe (MTL)
      including parahippocampal and anterior temporal regions. The current results
      provide neuroimaging evidence supporting that the MTL is involved in off-line
      memory consolidation of episodic memory. Moreover, this study may provide a
      paradigm for understanding of episodic memory deficit in Alzheimer's disease.

PMID- 22955146
TI  - Tibiofemoral contact mechanics following posterior root of medial meniscus tear,
      repair, meniscectomy, and allograft transplantation.
AB  - PURPOSE: The purposes of this study were to evaluate the effect on tibiofemoral
      contact mechanics of repair of the posterior root of the medial meniscus and the
      effect of meniscal allograft transplantation (MAT) with medial collateral
      ligament (MCL) release at different flexion angles. METHODS: Ten fresh-frozen
      human cadaveric knees (five pairs) were used. A digital pressure sensor was
      inserted by capsulotomy, and experiments were performed serially under the
      following six conditions, that is, with an intact medial meniscus (normal
      controls), with a root tear, after root repair, after total meniscectomy, after
      MAT, and after MAT plus MCL release. During each experiment, knees were
      positioned at 0 degrees , 30 degrees , 60 degrees , and 90 degrees  of flexion,
      and peak pressure (kPa) and contact area (cm2) were measured. RESULTS: At 0
      degrees  of flexion, contact pressure did not differ among the six experimental
      settings. However, at 30 degrees  and 60 degrees  of flexion, contact pressure
      differed significantly between root tear and root repair specimens (p = 0.04 and
      0.03, respectively), and between total meniscectomy and MAT specimens (p = 0.02
      and 0.03, respectively). On the other hand, mean contact pressures were different
      between normal (476.7 +/- 473.1 and 573.3 +/- 479.1 kPa) and root repair (575.7
      +/- 357.8 and 598.6 +/- 415.8), and between normal and MAT (635.7 +/- 437.4 and
      674.3 +/- 533.2). At 0 degrees , 30 degrees , 60 degrees , and 90 degrees  of
      flexion, contact areas differed significantly between normal and total
      meniscectomy specimens (p = 0.02, 0.01, 0.02, and 0.02, respectively), and
      between MAT and total meniscectomy specimens (p = 0.03, 0.02, 0.02, and 0.03,
      respectively). Contact areas differed significantly between root tear and root
      repair specimens at 60 degrees  of flexion (p = 0.04), and between normal control
      and root repair specimens at 60 degrees  and 90 degrees  of flexion (p = 0.03 and
      0.04, respectively). The effects of MAT plus MCL release on contact mechanics
      were not different from the effects of MAT alone (n.s.). CONCLUSIONS: Both
      meniscal root repair and transplantation of meniscus improved contact mechanics,
      but it did not appear that repair of the meniscal root or transplantation of
      meniscus restores the biomechanical function back to normal level. The MAT plus
      MCL release was similar to those after MAT alone. Therefore, it is better to
      preserve meniscus and MCL release could be done during the MAT.

PMID- 22955147
TI  - Response to 'Critical comments and questions to the publication "Getgood A,
      Collins B, Slynarski K, Kurowska E, Parker D, Engebretsen L, MacDonald PB,
      Litchfield R 2011 Short-term safety and efficacy of a novel high tibial osteotomy
      system: a case controlled study"'.

PMID- 22955148
TI  - [Plastic surgery of ears, eyebrows and eyelids].

PMID- 22955149
TI  - Infusion and oncology nursing: specialty practices united.

PMID- 22955150
TI  - Synergy in nursing care of the oncology patient.

PMID- 22955151
TI  - Building a clinical trial process in oncology.
AB  - Clinical trials offer patients the opportunity to participate in medical
      advancement, while providing access to the newest therapies, often at no
      additional cost. This is especially true in oncology, where rapid acceleration of
      research has created many promising treatment options for cancer patients.
      Administration of a clinical trial requires extensive education and collaboration
      to provide the highest quality of health care within a rapidly evolving
      environment. As an integral part of this team, the infusion nurse in the oncology
      setting is in a unique position to enhance patient safety and protection through
      effective use of clinical knowledge and patient assessment and advocacy skills.

PMID- 22955152
TI  - Biologic therapy.
AB  - Biologic therapy includes a diverse group of drugs that act directly on the
      immune system. Sometimes referred to as "targeted therapy," the biologics include
      cytokines and monoclonal antibodies. These agents can be genetically engineered
      versions of naturally occurring substances, or novel compounds used for the
      treatment of cancer and for nononcology diagnoses. This article provides
      information on the general types of biotherapy, an overview of how these drugs
      interact within the body, specific side effects, and nursing management.

PMID- 22955153
TI  - NIOSH safe handling of hazardous drugs guidelines becomes state law.
AB  - Although guidelines for protecting health care workers from the dangers of
      hazardous drugs have been in existence for more than 25 years, there is
      tremendous inconsistency in compliance by oncology professionals. One reason for
      the discrepancy is the voluntary, nonpunitive nature of these guidelines. In
      2012, Washington State became the first in the United States to mandate and
      enforce the National Institute for Occupational Safety and Health guidelines.

PMID- 22955154
TI  - Evaluation of safe infusion devices for antineoplastic administration.
AB  - Nurses endure daily low-level exposure to cytotoxic drugs, which can lead to
      significant absorption with potential harmful consequences. New sterile medical
      devices called cytotoxic safe infusion systems (CSISs), intended by their
      manufacturers to improve safety and quality of cytotoxic drug infusions, have
      been made commercially available. CSISs from 3 manufacturers were tested in 2
      cancer units and compared with standard infusion sets. The aim of this study is
      to evaluate the devices regarding occupational exposure, quality of the infusion,
      and economic aspects.

PMID- 22955155
TI  - Chronotherapeutic drug delivery.
AB  - Living organisms follow a circadian rhythm in which physiological processes such
      as hormonal secretion, metabolism, heart rate, and renal output are affected by
      the time of day. Chronotherapy coordinates drug delivery with the circadian
      rhythm to enhance effectiveness and mitigate adverse effects and is achieved by
      delivering a drug when the system is most susceptible. Cancer is a
      chronotherapeutic disorder. Cancer treatment requires high doses of intravenous
      medication to kill cancerous cells; however, normal cells are also killed,
      creating intolerable side effects. This review shows that chronotherapy can play
      a vital role in the quality of life and survival rate for oncology patients.

PMID- 22955157
TI  - Determination of the stacking order of curved few-layered graphene systems.
AB  - We report a facile method to efficiently visualize the atomic carbon network of
      curved few-layered graphitic systems including folded bi-layer graphene,
      nanoribbon edges and multi-walled carbon nanotubes (straight and bent), via the
      processing of aberration-corrected high-resolution transmission electron
      microscopy (AC-HRTEM) images. This technique is also able to atomically resolve
      the structure of overlapping graphene layers with different orientations, thus
      enabling us to determine the stacking order of multiple graphene layers. To the
      best of our knowledge, we are the first to identify the stacking order of a
      misoriented 4-layer closed-edge graphene and a metal-semiconductor double-walled
      carbon nanotube junction.

PMID- 22955158
TI  - Evidence of a role for fibrocyte and keratinocyte-like cells in the formation of
      hypertrophic scars.
AB  - Burn injuries affect millions of people every year, and dermal fibrosis is a
      common complication for the victims. This disfigurement has functional and
      cosmetic consequences and many research groups have made it the focus of their
      work to understand the mechanisms that underlie its development. Although
      significant progress has been made in wound-healing processes, the complexity of
      events involved makes it very difficult to come up with a single strategy to
      prevent this devastating fibrotic condition. Inflammation is considered one
      predisposing factor, although this phase is a necessary aspect of the wound
      healing process. Inflammation, driven by infiltrated immune cells, begins minutes
      after the burn injury and is the prevalent phase of wound healing in the early
      stages. Accompanying the inflammatory infiltrate, there is evidence that
      subpopulations of bone marrow-derived cells are also present. These populations
      include fibrocytes and keratinocyte-like cells, derivatives of CD14 monocytes, a
      component of the peripheral blood mononuclear cell infiltrate. There is evidence
      that these cells contribute to regeneration and repair of the wound site, but it
      is interesting to note that there are also reports that these cells can have
      adverse effects and may contribute to the development of dermal fibrosis. In this
      article, the authors present a review of the origin and transdifferentiation of
      these cells from bone marrow stem cells, the environments that direct this
      transdifferentiation, and evidence to support their role in fibrosis, as well as
      potential avenues for therapeutics to control their fibrotic effects.

PMID- 22955159
TI  - Toxic epidermal necrolysis: performance of SCORTEN and the score-based comparison
      of the efficacy of corticosteroid therapy and intravenous immunoglobulin combined
      therapy in China.
AB  - Toxic epidermal necrolysis (TEN) represents the most severe drug-related skin
      condition that is potentially life-threatening with no well-established
      treatments. The application of corticosteroid therapy is controversial, whereas
      recently intravenous immunoglobulin (IVIG) therapy is emerging as a promising new
      method. A severity-of-illness score for TEN (SCORTEN) has gained acceptance in
      some western countries. In this study, our objectives were to assess the
      applicability of SCORTEN in Chinese patients with TEN and to evaluate the
      efficacy of the combination therapy of IVIG and corticosteroid in these patients.
      We performed a retrospective review of data from 61 patients with TEN treated at
      our intensive care unit from 2000 to 2010 to assess the performance of SCORTEN.
      In particular, 55 patients between 2002 and 2010 were grouped as a series to
      compare the therapeutic effects of corticosteroid therapy and IVIG combined
      therapy contemporaneously. During this period, 16 patients were administered with
      corticosteroid therapy and 39 were treated with the combination therapy. An
      initial dose of 1.5 mg/kg/day of methylprednisolone was given to all TEN
      patients. The combination therapy was combined with a total dose of 2 g/kg IVIG
      within 5 days. Areas under receiver operating characteristic curves and Hosmer
      Lemeshow statistic were analyzed to illustrate the performance of SCORTEN. The
      comparison of the efficacy of the two therapies was conducted on the basis of
      clinical outcomes, standardized mortality ratio (SMR), and survival analysis. The
      overall actual mortality of patients between 2000 and 2010 was 16% (10/61),
      statistically insignificantly lower than predicted (24%, SMR = 67.98). Excellent
      discriminatory power (the areas under the receiver operating characteristic
      curves: 88.9, 88.2, 90.6%) and good calibration (P = .637, .833, .530) were found
      in all the groups. In patients admitted between 2002 and 2010, IVIG combined
      therapy showed a trend toward reducing the mortality rate (13%, SMR = 52.35),
      whereas corticosteroid monotherapy suggested no such difference (31%, SMR =
      123.92). Besides, the cumulative survival rates of the combination therapy were
      higher at almost all the levels of SCORTEN (P = .002), especially at the score of
      5 (P = 3.10 * 10-7). Compared with corticosteroid alone, the combination therapy
      arrested progression earlier (P = .013), although it did not significantly lead
      to a tapering of corticosteroid or a reduction of the time of hospitalization. We
      concluded that SCORTEN was generally applicable to Chinese patients with TEN. The
      comparison of the effect indicated that the combination therapy might achieve a
      better therapeutic effect than the administration of corticosteroid alone,
      especially in severe TEN patients.

PMID- 22955160
TI  - The impact of recent changes in smoke alarm legislation on residential fire
      injuries and smoke alarm ownership in New South Wales, Australia.
AB  - In 2006, New South Wales (NSW) state legislation changed from requiring smoke
      alarms in new houses only to all houses. We evaluated the impact of this
      legislative change on residential fire injury and smoke alarm ownership
      characteristics. Residential fire injuries for 2002 to 2010 were identified from
      hospitalization data for all hospitals in NSW. Data relating to smoke alarm
      ownership and demographic factors were obtained from the NSW Population Health
      Survey. Negative binomial regression analysis was used to analyze trends over
      time. Prior to the introduction of universal legislation, hospitalization rates
      were increasing slightly; however, following the introduction of legislation,
      hospitalization rates decreased by an estimated 36.2% (95% confidence interval
      [CI], 16.7-55.8) annually. Smoke alarm ownership increased from 73.3% (95% CI,
      72.5-74.2) prelegislation to 93.6% (95% CI, 93.1-94.2) 18 months postlegislation.
      Thirty percent of households reported testing their alarms regularly. Speaking a
      language other than English (relative risks [RRs], 1.82; 95% CI, 1.44-2.99),
      allowing smoking in the home (RR, 1.73; 95% CI, 1.31-2.27), and being part of the
      most disadvantaged socioeconomic group (RR, 1.47; 95% CI, 1.14-1.91) remain major
      risk factors for nonownership. Broadening the scope of state legislation has had
      a positive impact on residential fire-related hospitalizations and smoke alarm
      ownership. However, it is of concern that the legislation has been the least
      effective in increasing smoke alarm ownership among non-English-speaking
      households, in households where smoking is allowed, in low socioeconomic
      households, and that a high proportion of householders do not test their smoke
      alarms regularly. Targeted campaigns are needed to reach these high-risk groups
      and to ensure that smoke alarms are functional.

PMID- 22955161
TI  - Severe burn injuries induced by PUVA chemotherapy.
AB  - Psoralen-ultraviolet A (PUVA) chemotherapy is an established treatment for
      certain skin diseases. Burn injury is a serious complication of PUVA therapy.
      Reports regarding this complication are limited. The aim of this study was to
      determine the management and outcome of severe PUVA burns. A retrospective review
      of the medical records of PUVA burns treated at our burn center from 2000 to 2010
      was conducted. Data collected included age, sex, condition, mode of PUVA, site,
      surface area involved, depth of burns, onset of reactions, treatment, and
      inpatient stay. To evaluate the incidence of this severe complication, a survey
      of all listed burn care units in Germany, Austria, and Switzerland as well as the
      legal advisory boards of the medical associations of the federal states of
      Germany was conducted. The conditions leading to photochemotherapy were three
      cases of psoriasis vulgaris and one case of severe chronic graft vs host disease.
      All patients received oral psoralen. Incorrect handling of the radiation system
      was the reason for all burns. The mean affected TBSA was 73+/-18%. All patients
      were treated conservatively and healed without surgical intervention. Burn injury
      is a serious and preventable complication of PUVA photochemotherapy. Patients
      should be advised regarding the potential risk of major burns. Care should be
      given to not exceed the safe dose of psoralen. Burn care specialists must
      restrain surgical intervention as even deep partial thickness PUVA burns have the
      potential to heal spontaneously.

PMID- 22955162
TI  - The use of laser Doppler imaging as a predictor of burn depth and hypertrophic
      scar postburn injury.
AB  - Hypertrophic scarring (HTS) is a fibroproliferative disorder that commonly
      develops after severe burn injuries. Overexpression of transforming growth factor
      beta (TGF-beta) by an increased number of fibrocytes has been associated with
      increased extracellular matrix molecule expression leading to HTS. The most
      widely accepted adjuvant to clinical assessment of burn depth is laser Doppler
      imaging (LDI) and may predict injury to the dermis that corresponds to cellular
      and molecular changes associated with HTS. A prospective, blinded, control trial
      was performed comparing LDI and clinical assessment for the decision to operate.
      Immunohistochemistry and real-time reverse transcription polymerase chain
      reaction was performed to determine whether there is a correlation between
      histological assessment of burn depth and LDI, and the presence of fibrocytes was
      detected using confocal microscopy. The positive predictive value for a burn
      requiring a graft was calculated to be >90%. Immunohistochemistry on biopsy
      samples revealed an increased expression of TGF-beta, connective tissue growth
      factor, heat shock protein 47, and collagen type I in deep burn wounds compared
      to superficial burns. Using the fibrocyte-specific markers procollagen type I and
      lymphocyte-specific protein-1, there was an increased number of fibrocytes in
      deep burn areas compared to superficial burn. In deep burn injuries, increased
      infiltration of fibrocytes occurs leading to an overexpression of TGF-beta1 and
      connective tissue growth factor. More importantly, LDI was >90% accurate at
      predicting the need for excision and grafting. The accuracy of the decision to
      debride deep dermal burns to avoid HTS using both clinical parameters and LDI was
      supported by histological and biochemical measurements.

PMID- 22955163
TI  - Association of rhabdomyolysis with renal outcomes and mortality in burn patients.
AB  - The contribution of rhabdomyolysis to acute kidney injury (AKI) in the context of
      burn injury is poorly studied. We sought to determine the impact of
      rhabdomyolysis on AKI (defined by the AKI Network classification), renal
      replacement therapy (RRT), and death. Patients admitted to the burn unit at our
      institution were examined. Information on sex, age, presence of inhalation
      injury, electrical burn, percentage TBSA burned, percentage of full-thickness
      burns, Injury Severity Score, and peak creatine kinase (CK) were recorded. These
      variables were examined via multivariate logistic regression analysis against AKI
      Network stage, RRT, and death. Of 1973 consecutive admissions meeting the
      inclusion criteria, 525 met our eligibility criteria. Log peak CK was found to be
      correlated with any stage of AKI (odds ratio [OR], 1.71; 95% confidence interval
      [CI], 1.36-2.16; P < .0001), moderate to severe AKI (OR, 2.09; 95% CI, 1.40-3.11;
      P = .0003), need for RRT (OR, 1.67; 95% CI, 1.16-2.40; P = .0057), and mortality
      (OR, 1.49; 95% CI, 1.01-2.20; P = .0441), after adjustment. Each 10-fold increase
      in peak CK was associated with a 70% increase in the odds of AKI, more than a
      100% increase in the odds of moderate to severe AKI, a nearly 70% increase in the
      odds of RRT, and an almost 50% increase in the odds of mortality in patients with
      burn injury.

PMID- 22955164
TI  - Amyloid fibril formation from human and bovine serum albumin followed by quasi
      simultaneous Fourier-transform infrared (FT-IR) spectroscopy and static light
      scattering (SLS).
AB  - Human and bovine serum albumins are widely known proteins that can form amyloid
      fibrils under destabilizing conditions. Use of well-known proteins with easily
      controlled aggregation process, and comparison of these processes for similar
      proteins from different species, could help elucidate the nature of the
      aggregation process implicated in many degenerative diseases, for example
      Alzheimer's, Parkinson's, or type II diabetes. In this work both amyloidogenic
      mechanisms have been studied by use of infrared spectroscopy in combination with
      static light scattering, enabling analysis of intra and intermolecular processes
      and measurement of prefibril and fibril growing quasi-simultaneously. Deeper
      insight into the rearrangements of the secondary structure of the proteins
      concomitant with the aggregation process has also been gained by mathematical
      analysis of the infrared spectra by two-dimensional correlation spectroscopy
      (2DCOS).

PMID- 22955165
TI  - Human tissue authority responds to research in transplantation: update from the
      UK Donation Ethics Committee.

PMID- 22955166
TI  - Response to "in vitro and in vivo proof of tolerance after two-step
      haploidentical bone marrow and kidney transplantation of the same donor".

PMID- 22955168
TI  - A new israeli transplant law.

PMID- 22955169
TI  - Preservation of fertility in women undergoing reduced-intensity conditioning
      allogeneic transplantation with a fludarabine-based regime.

PMID- 22955170
TI  - Outcome of renal transplantation in patients with both ANCA and anti-GBM
      antibodies.

PMID- 22955171
TI  - In vitro PUVA treatment preferentially induces apoptosis in alloactivated T
      cells.

PMID- 22955172
TI  - Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose
      proportionality, food effect, and racial sensitivity.
AB  - PURPOSE: Lenalidomide is an immunomodulatory drug with efficacy in various
      hematological malignancies. The purpose of these studies was to evaluate the
      single-dose pharmacokinetics of lenalidomide, including dose proportionality,
      food effect, and racial sensitivity. METHODS: Three studies were conducted
      including a total of 58 healthy subjects: a randomized, single-blind, alternating
      group, single-ascending dose study; a randomized, two-way crossover food effect
      study; and a randomized, double-blind, two-group, within-subject, single
      ascending dose study. RESULTS: Oral absorption of lenalidomide was rapid and the
      maximum plasma concentration (C (max)) was observed approximately 1 h post-dose.
      Co-administration with a high-fat meal reduced the area under the concentration
      time curve (AUC) and C (max) by approximately 20 and 50 %, respectively, and
      delayed time to C (max) (t (max)) by 1.63 h. However, phase III trials were dosed
      without regard to food; therefore, clinical relevance of the food effect was
      minimal. The terminal elimination half-life (t (1/2)) was 3-4 h at doses up to 50
      mg and was not affected by food. The AUC and C (max) were proportional to
      lenalidomide single doses (5-400 mg), and total and renal clearance were dose
      independent. The R- to S-lenalidomide ratio in plasma was stable over time,
      approximately 45-55 % of total drug. There were no differences in pharmacokinetic
      parameters, dose-exposure relationship, or enantiomeric ratio, between Japanese
      and Caucasian subjects. CONCLUSION: Lenalidomide displayed linear
      pharmacokinetics from doses 5-400 mg in healthy subjects. Although food reduced
      bioavailability, this was not considered clinically relevant. Lenalidomide was
      generally well tolerated in both ethnic groups.

PMID- 22955173
TI  - Current world literature.

PMID- 22955175
TI  - Susceptibility of Staphylococcus aureus bacteremia strains to different skin
      derived antimicrobial proteins.
AB  - Staphylococcus aureus is a major human pathogen causing cutaneous infections to
      life-threatening bacteremia. These infections are often caused by strains derived
      from the own microflora suggesting that a disturbed epidermal barrier may promote
      invasion of S. aureus. Antimicrobial peptides and proteins (AMP) such as human
      beta-defensin-3 and RNase 7 contribute to control the colonization of S. aureus
      on the skin surface. This leads to the hypothesis that strains with a decreased
      susceptibility toward skin-derived AMP may better overcome the innate cutaneous
      defence barrier increasing the possibility of invading into the blood stream. To
      address this hypothesis we determined whether S. aureus strains from bacteremia
      patients are less susceptible to various skin-derived AMP than strains from
      healthy carriers. No differences in the AMP-killing activity against bacteremia
      derived S. aureus and control strains were detected suggesting that the onset of
      S. aureus bacteremia is not based on the varying susceptibilities against skin
      derived AMP.

PMID- 22955176
TI  - APOE4 predicts amyloid-beta in cortical brain biopsy but not idiopathic normal
      pressure hydrocephalus.
AB  - OBJECTIVE: To investigate the association of apolipoprotein E (APOE) genotype,
      especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus
      (iNPH) and (2) amyloid-beta (Abeta) plaques in cortical brain biopsies of
      presumed NPH patients with and without a final clinical diagnosis of Alzheimer's
      disease (AD). METHODS: 202 patients with presumed NPH were evaluated by
      intraventricular pressure monitoring and frontal cortical biopsy immunostained
      against Abeta (134 semiquantified by Abeta plaques/mm2). The 202 patients and 687
      cognitively healthy individuals were genotyped for APOE. The final clinical
      diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive,
      16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53
      others. RESULTS: The APOE genotypes distributed similarly in the 94 shunt
      responsive and 16 non-responsive iNPH patients and healthy controls. In
      multivariate analysis, the APOE4 allele correlated independently with Abeta
      plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4
      allele in presumed NPH predicted later AD as follows: sensitivity 61%;
      specificity 77%; positive predictive value 37%; negative predictive value 90%.
      CONCLUSION: In presumed NPH patients, APOE4 associates independently with the
      presence of Abeta plaques in the frontal cortical biopsy. APOE4 is not a risk
      factor for iNPH and does not predict the response to shunt. Our data further
      support the view that the iNPH syndrome is a distinct dementing disease. TRIAL
      REGISTRATION NUMBER: Kuopio NPH Registry (http://www.uef.fi/nph).

PMID- 22955177
TI  - Dissociations and similarities in motor intention and motor awareness: the case
      of anosognosia for hemiplegia and motor neglect.
AB  - OBJECTIVES: To confront motor awareness in anosognosia for hemiplegia (AHP),
      where paralyzed patients deny their motor impairment, and in motor neglect (MN),
      where non-paralyzed patients behave as if they were paretic. METHODS: Eight right
      brain-damaged-patients, 4 hemiplegic (2 with and 2 without AHP) and 4 non
      hemiplegic (2 with only perceptual-neglect and 2 with also MN) were evaluated
      with a bimanual motor battery, before and after examiner's reinforcement to use
      the contralesional limb. The requested bimanual movements could be either
      symmetric or asymmetric, either intransitive or transitive (with/without
      objects). We compared the examiner's evaluation of patients' performance with the
      patients' self-evaluation of their own motor capability (explicit knowledge). We
      also evaluated the presence/absence of compensatory unimanual strategies that, if
      present, suggests implicit knowledge of the motor deficit. RESULTS: We found
      significant differences between conditions only in MN patients, whose performance
      was better after the examiner's reinforcement than before it, during symmetric
      than asymmetric movements and during intransitive than transitive movements. As
      for motor awareness, we found a lack of explicit and implicit knowledge in both
      AHP and MN patients. CONCLUSION: Although different in terms of motor intention
      and motor planning, AHP and MN are both characterised by anosognosia for the
      motor impairment.

PMID- 22955178
TI  - New palladium and platinum complexes with bioactive 3,5-diacetyl-1,2,4-triazol
      bis(4-cyclohexyl thiosemicarbazone) ligand: chemistry, antiproliferative activity
      and preliminary toxicity studies.
AB  - The preparation and characterization of the new 3,5-diacetyl-1,2,4-triazol bis(4
      cyclohexyl thiosemicarbazone) ligand, H(5)L(1), is described. Treatment of
      H(5)L(1) with K(2)PtCl(4) gave the dinuclear complex [Pt(H(3)L(1))](2), 1, but
      using MCl(2)(PPh(3))(2) where M = Pd or Pt, mononuclear complexes 2 and 3, of
      general formula [M(H(3)L(1))PPh(3)], were obtained. Subsequent reaction of the
      [Pd(H(3)L(1))PPh(3)] complex with PdCl(2)(PPh(3))(2) yielded a new dinuclear
      complex [(PPh(3))Pd(H(2)L(1))PdCl], 4. All compounds have been characterized by
      elemental analysis and FAB(+) spectrometry and by IR and NMR spectroscopy. The
      molecular structures of mononuclear complexes 2 and 3 and dinuclear complex 4
      have been determined by X-ray crystallography. The new compounds synthesized have
      been evaluated for antiproliferative activity in vitro against NCI-H460, HepG2,
      MCF-7, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest
      that the H(5)L(1) ligand and [Pt(H(3)L(1))](2), complex 1, may be endowed with
      important cytotoxic properties since they are capable of not only circumventing
      cisplatin resistance in A2780cisR but also exhibit antiproliferative activity in
      NCI-H460. The interactions of these compounds with calf thymus DNA were
      investigated by UV-vis absorption and a nephrotoxic study, in LLC-PK1 cells, has
      also been carried out.

PMID- 22955179
TI  - Circulating miRNAs: messengers on the move in cardiovascular disease.

PMID- 22955183
TI  - New highly soluble dimedone-derived iodonium ylides: preparation, X-ray
      structure, and reaction with carbodiimide leading to oxazole derivatives.
AB  - Highly soluble dimedone-derived o-alkoxyphenyliodonium ylides have been prepared
      and characterized by single crystal X-ray diffraction. These new iodonium ylides
      are useful reagents for the preparation of oxazole derivatives by reaction with
      carbodiimides.

PMID- 22955184
TI  - Early androgens, activity levels and toy choices of children in the second year
      of life.
AB  - The hypothesis that stronger preferences for active play styles contribute to
      stronger preferences for male-typical toys was examined in 47 boys and 37 girls
      at 19-months of age using ambulatory monitoring technology (i.e., actigraphy) to
      measure activity levels during contact with male-typical, female-typical, and
      gender-neutral toys. Digit ratios and salivary testosterone levels were measured
      earlier in children at 3-4 months of age. There were no significant sex
      differences in digit ratios, salivary testosterone levels, or overall activity
      levels during toy play. In contrast, contact times showed large sex differences
      in infants' toy preferences. The within-sex comparisons showed that infant girls
      had significant preferences for female-typical toys over male-typical toys,
      whereas infant boys showed only a small preference for male-typical toys over
      female-typical toys. More male-typical digit ratios in early infancy predicted
      higher activity counts during toy play and less female-typical toy preferences in
      girls. However, in both sexes, activity levels were unrelated to toy preferences
      suggesting that factors other than activity level preferences contribute to the
      early emergence of gender-linked toy preferences.

PMID- 22955185
TI  - Global cardiovascular disease prevention: a call to action for nursing executive
      summary.
AB  - The global epidemic of cardiovascular disease (CVD) calls for multidisciplinary
      and multiprofessional approaches to the management of this condition, with
      strategic emphasis on prevention, treatment, and control. In addition, there is
      increasing recognition that effective prevention and management of CVD requires a
      diverse workforce skilled in the social, environmental, and policy determinants
      of health. Nowhere are these approaches and strategies brought together and more
      closely aligned than in the field of preventive cardiovascular nursing. This
      executive summary of "Global Cardiovascular Prevention: A Call to Action for
      Nursing" includes key points from the 6 papers written by the Preventive
      Cardiovascular Nurses Association and published in July-August 2011 as a
      supplement to the Journal of Cardiovascular Nursing and the European Journal of
      Cardiovascular Nursing. This supplement addresses innovative efforts to stem the
      current global epidemic of CVD and emphasizes the need for effective team-based
      interventions for lifestyle and behavior changes across the life span. Social
      solutions, strategies for working with key players to develop interactive models,
      as well as coordinated multilevel policies, partnerships, and programs that are
      culturally relevant and context specific are examined. Such approaches are
      urgently needed to reduce death and disability from CVD in the United States and
      globally. Nurse leaders and other members of the healthcare team are well
      positioned internationally to meet these challenges. 

PMID- 22955186
TI  - Comparison of software programs for the assessment of left ventricular ejection
      fraction using 99mTc-tetrofosmin-gated SPECT/CT:  correlation with equilibrium
      radionuclide ventriculography in the Indian population.
AB  - OBJECTIVE: The goal of this study was to compare Emory Cardiac Toolbox (ECTb),
      quantitative gated SPECT (QGS), four-dimensional single photon emission computed
      tomography (4D-MSPECT) and Myometrix cardiac software programs for the assessment
      of left ventricular ejection fraction (LVEF) using 99mTc-tetrofosmin-gated
      SPECT/CT [myocardial perfusion SPECT (MPS)] and correlate them with the LVEF
      values derived from equilibrium radionuclide ventriculography (ERNV) in patients
      with known/suspected coronary artery disease (CAD). MATERIALS AND METHODS: A
      total of 109 patients (80 men, 29 women) were recruited into the study. Fifty
      five patients had known CAD and 54 were referred with suspicion of CAD. All the
      patients underwent ERNV and MPS as per the standard protocol. ERNV was processed
      using the vendor-provided 'EF analysis' and gated MPS was processed using
      individual software programs. RESULTS: The mean LVEF on ERNV was 47.9 +/- 15.5%.
      The mean LVEF values for ECTb, QGS, 4D-MSPECT and Myometrix were 51.5 +/- 19.6,
      51.0 +/- 18.6, 57.1 +/- 19.3 and 49.7 +/- 19%, respectively. On correlation
      analysis, a very strong positive correlation was observed between LVEF values
      derived by ERNV and those derived by the MPS software programs: ECTb (r=0.842,
      P<0.0001), QGS (r=0.835, P<0.0001), 4D-MSPECT (r=0.830, P<0.0001) and Myometrix
      (r=0.875, P<0.0001). Significant correlation was also seen for LVEFs among the
      four software programs. Normal cutoff values for ejection fraction on ECTb, QGS,
      4D-MSPECT and Myometrix were 56, 52, 54 and 51%, respectively, using a 50% or
      more cutoff value on ERNV. CONCLUSION: A strong correlation was observed among
      ECTb, QGS, 4D-MSPECT and Myometrix software programs when compared with ERNV and
      also between them for assessment of LVEF. However, there are subtle differences
      in the objective values of ejection fraction generated by individual software,
      which must be taken into account for clinical studies.

PMID- 22955187
TI  - 131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin's lymphoma: 
      radiation dose to the testes.
AB  - PURPOSE: To investigate radiation doses to the testes delivered by a radiolabeled
      anti-CD20 antibody and its effects on male sex hormone levels. MATERIALS AND
      METHODS: Testicular uptake and retention of (131)I-tositumomab were measured, and
      testicular absorbed doses were calculated for 67 male patients (54 +/- 11 years
      of age) with non-Hodgkin's lymphoma who had undergone myeloablative
      radioimmunotherapy (RIT) using (131)I-tositumomab. Time-activity curves for the
      major organs, testes, and whole body were generated from planar imaging studies.
      In a subset of patients, male sex hormones were measured before and 1 year after
      the therapy. RESULTS: The absorbed dose to the testes showed considerable
      variability (range = 4.4-70.2 Gy). Pretherapy levels of total testosterone were
      below the lower limit of the reference range, and post-therapy evaluation
      demonstrated further reduction [4.6 +/- 1.8 nmol/l (pre-RIT) vs. 3.8 +/- 2.9
      nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the
      testes (>= 25 Gy) showed a greater reduction [4.7 +/- 1.6 nmol/l (pre-RIT) vs.
      3.3 +/- 2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower
      doses (<25 Gy), who showed no significant change in total testosterone levels.
      CONCLUSION: The testicular radiation absorbed dose varied highly among individual
      patients. Patients receiving higher doses to the testes were more likely to show
      post-RIT suppression of testosterone levels.

PMID- 22955188
TI  - Effect of mild diarrhea on tacrolimus exposure.
AB  - BACKGROUND: Diarrhea is a frequent adverse event in patients treated with the
      combination of tacrolimus and mycophenolate mofetil (MMF). In case of severe
      diarrhea, the total exposure to tacrolimus can substantially increase, which is
      reflected in a rise of the predose trough level (C0). In mild diarrhea (two to
      three stools per day), an increased exposure might occur without trough levels
      exceeding the target range, resulting in "silent" chronic tacrolimus
      overexposure. The aim was to assess the degree of unnoticed tacrolimus
      overexposure in renal transplant patients with mild diarrhea while on treatment
      with tacrolimus and MMF. METHODS: A prospective pharmacokinetic study was
      performed in 12 recipients of a renal allograft using a combination of tacrolimus
      and MMF with mild diarrhea and in 12 controls. Tacrolimus levels were assessed by
      a validated dried blood spot method for sampling and measurement. RESULTS: The C0
      did not differ between patients with mild diarrhea and controls (mean [95%
      confidence interval], 9.6 ug/L [8.6-10.9 ug/L] and 8.3 ug/L [6.9-9.9 ug/L]). In
      addition, there was no significant difference in the 12-hr area under the curve
      between patients with mild diarrhea and controls (185.6 ug. h/L [153.6-224.2
      ug.h/L] vs. 170.5 ug.h/L [137.2-221.8 ug.h/L]). As a result, the ratio between
      the 12-hr area under the curve and C0 was similar in both groups (19.2 [17.5
      21.1] vs. 20.6 [19.0-22.4]). The intraindividual variability in tacrolimus
      exposure was limited and not affected by the presence of mild diarrhea.
      CONCLUSIONS: We found no evidence for the presence of hidden tacrolimus
      overexposure in patients with mild diarrhea while on treatment with tacrolimus
      and MMF.

PMID- 22955189
TI  - Cellular infiltrates and NFkappaB subunit c-Rel signaling in kidney allografts of
      patients with clinical operational tolerance.
AB  - BACKGROUND: Nuclear factor kappa B (NFkappaB) plays a potential role in tolerance
      by orchestrating onset and resolution of inflammation and regulatory T cell
      differentiation through subunit c-Rel. We characterized cellular infiltrates and
      expression of NFkappaB1, c-Rel and its upstream regulators phosphatidylinositol 3
      kinase/RAC-alpha serine/threonine kinase, in allograft biopsies from patients
      with spontaneous clinical operational tolerance (COT). METHODS: Paraffin-fixed
      kidney allograft biopsies from 40 patients with COT (n=4), interstitial rejection
      (IR; n=12), borderline changes (BC; n=12), and long-term allograft function
      without rejection (NR; n=12) were used in the study. Cellular infiltrates and
      immunohistochemical expression of key proteins of the NFkappaB pathway were
      evaluated in the cortical tubulointerstitium and in cellular infiltrates using
      digital image analysis software. Results were given as mean+/-SEM. RESULTS:
      Biopsies from patients with COT exhibited a comparable amount of cellular
      infiltrate to IR, BC, and NR (COT, 191+/-81; IR, 291+/-62; BC, 178+/-45; and NR,
      210+/-42 cells/mm) but a significantly higher proportion of forkhead box P3
      positive cells (COT, 11%+/-1.7%; IR, 3.5%+/-0.70%; BC, 3.4%+/-0.57%; and NR,
      3.7%+/-0.78% of infiltrating cells; P=0.02). c-Rel expression in cellular
      infiltrates was significantly elevated in IR, BC, and NR when analyzing the
      number of positive cells per mm (P=0.02) and positive cells per infiltrating
      cells (P=0.04). In contrast, tubular PI3K and c-Rel expression were significantly
      higher in IR and BC but not in NR compared with COT (P=0.03 and P=0.006,
      respectively). With RAC-alpha serine-threonine kinase, similar tendencies were
      observed (P=0.2). CONCLUSIONS: Allografts from COT patients show significant
      cellular infiltrates but a distinct expression of proteins involved in the
      NFkappaB pathway and a higher proportion of forkhead box P3-positive cells.

PMID- 22955190
TI  - The 40th anniversary of SNACC: celebrating a young and dynamic organization that
      is here to stay.

PMID- 22955191
TI  - The history of neuroanesthesiology: the people, pursuits, and practices.
AB  - Neuroanesthesiology has a rich history. Although advances in research and
      clinical practice were cornerstones for the development of this field, other
      equally critical factors came into play. These include the development of
      subspecialty societies, formal dissemination of information through textbooks and
      journal publications, and, most importantly, strong leadership. This article
      reviews important advances within the subspecialty and many individuals behind
      those advances. The analysis and speculative synthesis provide insights into the
      current status of neuroanesthesiology and possible directions for the
      subspecialty's future.

PMID- 22955192
TI  - Snapshot of 1973 and 1974: critical thinkers and contemporary research ideas in
      neurosurgical anesthesia during the first years of SNACC.
AB  - The year 2012 marks the 40th anniversary of the Society of Neuroscience in
      Anesthesiology and Critical Care (SNACC). To celebrate this occasion, we provide
      a review, speculative synthesis, and commentary addressing research relevant to
      neurosurgical anesthesiology in 1973 and 1974--the early years of SNACC. We
      address topics such as effects of anesthetic drugs, neuroprotection, cerebral
      physiology, and monitoring as they relate to the perioperative care of
      neurosurgical patients or patients experiencing or at risk for neurological
      disorders. Our hypothesis is that a review of these publications will identify
      the foundations of research and practice concepts that persist until today and
      will also identify concepts that have dwindled or outright disappeared.

PMID- 22955193
TI  - Osmotherapy:  pros and cons.

PMID- 22955194
TI  - PRO: osmotherapy for the treatment of acute intracranial hypertension.
AB  - Persisting severe brain edema causes intracranial hypertension and is associated
      with poor patient outcome. The treatment of acute intracranial hypertension is
      complex and multimodal. The most important options for medical treatment include
      controlled ventilation and osmotherapy, maintenance of brain and body
      homeostasis, and sedation. Osmotherapy is recommended in all relevant guidelines.
      The 2 osmotic agents most frequently used are mannitol and hypertonic saline.
      Both reduce intracranial pressure and improve cerebral perfusion and cerebral
      oxygen delivery. However, hypertonic saline seems advantageous over mannitol in
      many situations. In multitrauma patients, hypertonic saline contributes to
      hemodynamic stabilization and to the prevention of secondary insults. In
      addition, hypertonic saline has neurohumoral and immunologic effects, which may
      be beneficial in cerebral resuscitation.

PMID- 22955195
TI  - Osmotherapy in brain edema:  a questionable therapy.
AB  - Despite the fact that it has been used since the 1960s in diseases associated
      with brain edema and has been investigated in >150 publications on head injury,
      very little has been published on the outcome of osmotherapy. We can only
      speculate whether osmotherapy improves outcome, has no effect on outcome, or
      leads to worse outcome. Here we describe the action and potentially beneficial
      and adverse effects of the 2 most commonly used osmotic solutions, mannitol and
      hypertonic saline, and present some critical aspects of their use. There is a
      well-documented transient intracranial pressure (ICP)-reducing effect of
      osmotherapy, but an adverse rebound increase in ICP after its withdrawal has been
      discussed extensively in the literature and is an expected pathophysiological
      phenomenon. From side effects related to renal and pulmonary failure, electrolyte
      disturbances, and a rebound increase in ICP, osmotherapy can be negative for
      outcome, which may explain why we lack scientific support for its use. These
      drawbacks, and the fact that the most recent Cochrane meta-analyses of
      osmotherapy in brain edema and stroke could not find any beneficial effects on
      outcome, make routine use of osmotherapy in brain edema doubtful. Nevertheless,
      the use of osmotherapy as a temporary measure may be justified to acutely prevent
      brain stem compression until other measures, such as evacuation of space
      occupying lesions or decompressive craniotomy, can be performed. This article is
      the Con part in a Pro-Con debate in the present journal on the general routine
      use of osmotherapy in brain edema.

PMID- 22955198
TI  - NMR, DFT and luminescence studies of the complexation of Al(III) with 8
      hydroxyquinoline-5-sulfonate.
AB  - Multinuclear ((1)H, (13)C and (27)Al) magnetic resonance spectroscopy (1D and
      2D), DFT calculations and fluorescence have been used to study the complexation
      of 8-hydroxyquinoline-5-sulfonate (8-HQS) with Al(III). The study combines the
      high sensitivity of luminescence techniques, the selectivity of multinuclear NMR
      spectroscopy with the structural details accessible through DFT calculations, and
      aims to provide a detailed understanding of the complexation between the Al(3+)
      ion and 8-HQS. A full speciation study has been performed and over the
      concentration region studied, the Al(3+) ion forms complexes with 8-HQS in an
      aqueous solution in the pH range 2-6. At higher pH, the extensive hydrolysis of
      the metal limits complexation. Using Job's method, three complexes were detected,
      with 1 : 1, 1 : 2 and 1 : 3 (metal : ligand) stoichiometries. These results are
      in agreement with those previously reported using potentiometric and
      electrochemical techniques. The geometries of the complexes are proposed based on
      the combination of NMR results with optimized DFT calculations. All the complexes
      in aqueous solutions at 25  degrees C are mononuclear species, and have an
      approximately octahedral geometry with the metal coordinated to one molecule of 8
      HQS and four molecules of water (1 : 1 complex), two molecules of 8-HQS and two
      molecules of water mutually cis (1 : 2 complex), and to three molecules of 8-HQS
      in non-symmetrical arrangement (mer-isomer), for the 1 : 3 (metal : ligand)
      complex. On binding to Al(III), 8-HQS shows a more marked fluorescence than the
      weakly fluorescent free ligand. In addition, as previously noted, there are
      marked changes in the absorption spectra, which support the use of 8-HQS as a
      sensitive optical sensor to detect Al(3+) metal ions in surface waters and
      biological fluids. These complexes also show potential for applications in
      organic light emitting diodes (OLEDs).

PMID- 22955199
TI  - Gingival fibromatosis with multiple unusual findings: report of a rare case.
AB  - Gingival fibromatosis is a rare disease, especially its syndromic form. Here, we
      review the literatures on gingival fibromatosis and briefly summarize some
      characters on clinical, etiological, genetic and histopathological aspects. We
      also present a rare case of gingival fibromatosis with multiple unusual findings
      in a 21-year-old man. And we differentiate it from some well-known syndromes
      including gingival fibromatosis. Maybe it implies a new syndrome within the
      spectrum of those including gingival fibromatosis.

PMID- 22955200
TI  - Vitamin K antagonists. Ready to be replaced?
AB  - For the last decades, anticoagulation for stroke prevention in atrial
      fibrillation (AF) as well as for the prophylaxis and long-term treatment of
      venous thromboembolism has been entirely based on vitamin K antagonists (VKA).
      Although very effective under optimal conditions, long-term treatment with these
      drugs is flawed by the fact that the time in the therapeutic range frequently is
      suboptimal due to biological factors, drug interactions and compliance. The
      direct thrombin inhibitor dabigatran, as well as the direct FXa inhibitors
      rivaroxaban and apixaban provide more consistent anticoagulation and have proven
      their efficacy and safety against VKAs in several large scale randomized clinical
      trials for stroke prevention in atrial fibrillation as well as for the treatment
      and prevention of venous thromboembolism. In view of these convincing data and
      other advantages such as the lack of mandatory monitoring and only few drug
      interactions, VKAs will most likely be replaced in a majority of patients for
      these indications. Based on the most recent trial evidence, the current review
      discusses the role of VKA treatment and that of the novel anticoagulants.

PMID- 22955201
TI  - Inflaming attraction by RNA.

PMID- 22955202
TI  - Interview with Steve Davies.

PMID- 22955203
TI  - Designing and fabricating of surface-enhanced Raman scattering substrate with
      high density hot spots by polyaniline template-assisted self-assembly.
AB  - In general, the procedures for producing a high density hot spots structure
      should be stable, inexpensive, and easy to make. It still remains a grand
      challenge to assemble silver or gold nanoparticles (Au NPs) with well-defined hot
      spots for SERS detection. In this study, we present a very simple method for
      designing and fabricating a surface-enhanced Raman scattering (SERS) substrate
      with high density hot spots, using large area positively charged polyaniline
      (PANI) nanofibers as template to assemble negatively charged Au NPs. In order to
      obtain the optimized SERS-active substrates, different experiments to synthesize
      diverse Au/PANI with different sizes of Au NPs from about 50, 30 to 15 nm were
      carried out. The results revealed that the PANI nanofibers were fully coated by
      the ~15 nm Au NPs, forming a high density Au/PANI SERS substrate. The results
      evidence that we can obtain stable and sensitive SERS measurements.

PMID- 22955205
TI  - Intraplaque neovascularization and hemorrhage:  markers for cardiovascular risk
      stratification and therapeutic monitoring.
AB  - Atherosclerotic disease results in major clinical events and remains a leading
      cause of morbidity and mortality in the western World. Atherosclerotic plaques
      have a heterogeneous presentation. Atherosclerotic plaques with a vulnerable
      phenotype have been associated with an increased risk for cardiovascular
      complications. Intraplaque neovascularization and hemorrhage are
      histopathological features that have been linked with the vulnerable plaque. The
      role of intraplaque neovascularization and hemorrhage in plaque destabilization
      and lesion progression has gained serious interest. Intraplaque
      neovascularization and hemorrhage have been correlated with the occurrence of
      prior cardiovascular events and have predictive value for the occurrence of
      future cardiovascular events. Pharmacological interventions showed an inhibiting
      effect of lipid-lowering drugs on plaque neovascularization. Imaging modalities
      such as contrast-enhanced ultrasound or MRI are able to visualize intraplaque
      neovascularization and hemorrhage noninvasively. Consequently, detection of
      intraplaque neovascularization and hemorrhage visualized with noninvasive imaging
      might improve the stratification of 'high-risk' patients.

PMID- 22955206
TI  - Imaging of intraplaque haemorrhage.
AB  - Intraplaque hemorrhage (IPH) is an important co-factor for plaque progression and
      rupture. So far noninvasive MRI has shown promise for the in-vivo identification
      of IPH and for the prediction of plaque instability. Intravascular imaging
      techniques such as intravascular ultrasound or optical coherence tomography (OCT)
      cannot distinguish between IPH and other plaque components. However, OCT has the
      unique ability to identify microvessels located in the lipid core of
      atherosclerotic plaque due to its high resolution (around 20 MUm). Microvessels
      are known to be the main source of blood extravasation due to their anatomically
      compromised structure. Coronary plaques with a high microvessel density undergo
      rapid plaque progression and are often associated with other features of plaque
      instability such as inflammatory cells. The combination of data from both MRI and
      OCT studies will allow a better understanding of the mechanism of plaque
      destabilization and the pathophysiology of cardiovascular events.

PMID- 22955207
TI  - Alarm!!! A UFO inside the heart.
AB  - An 8-year-old asymptomatic child was referred for surgical repair of coronary
      sinus atrial septal defect resulting in significant left-to-right shunt and right
      chamber volume overload. The septal fenestration was located near to its drainage
      site into the right atrium. Due to this seemingly favourable anatomy,
      transcatheter closure of the septal defect was performed using an Amplatzer
      Septal Occluder device. The echocardiographic postprocedural evaluation imaged
      the occluding device almost perpendicular to the atrial septum, seemingly
      floating above the mitral valve orifice, like an alien spaceship inside the
      heart.

PMID- 22955208
TI  - Pigtail catheter fracture and embolization into the abdominal aorta:  an
      extremely rare angiographic complication.
AB  - Coronary angiography is a widely used diagnostic method for coronary artery
      disease. In clinical practice, although complications of the procedure often
      involve the vascular access point, there is no previous report of the fracture
      and embolization of the distal tip of a pigtail catheter. Herein, we present the
      case of a 51-year-old woman whose left ventriculography was interrupted by
      fracture of the curved tip of a pigtail catheter, which remained at the renal
      artery level in the abdominal aorta.

PMID- 22955209
TI  - Fab-arm exchange: what's in a name?

PMID- 22955210
TI  - Hyaluronidase treatment of synovial fluid to improve assay precision for
      biomarker research using multiplex immunoassay platforms.
AB  - Synovial fluid (SF) is a difficult biological matrix to analyse due to its
      complex non-Newtonian nature. This can result in poor assay repeatability and
      potentially inefficient use of precious samples. This study assessed the impact
      of SF treatment by hyaluronidase and/or dilution on intra-assay precision using
      the Luminex and Meso Scale Discovery (MSD) multiplex platforms. SF was obtained
      from patients with knee osteoarthritis at the time of joint replacement surgery.
      Aliquots derived from the same sample were left untreated (neat), 2-fold diluted,
      4-fold diluted or treated with 2mg/ml testicular hyaluronidase (with 2-fold
      dilution). Preparation methods were compared in a polysterene-bead Luminex 10
      plex (N=16), magnetic-bead Luminex singleplex (N=7) and MSD 4-plex (N=7). Each
      method was assessed for coefficient of variation (CV) of replicate measurements,
      number of bead events (for Luminex assays) and dilution-adjusted analyte
      concentration. Percentage recovery was calculated for dilutions and HAse
      treatment. Hyaluronidase treatment significantly increased the number of wells
      with satisfactory bead events/region (95%) compared to neat (48%, p<0.001) in the
      polystyrene-bead Luminex assay, but the magnetic-bead Luminex assay achieved >=50
      bead events irrespective of treatment method. Hyaluronidase treatment resulted in
      lower intra-assay CVs for detectable ligands (group average CV<10%) than neat, 2
      fold and 4-fold dilution (CV~25% for all, p<0.05) in both polystyrene- and
      magnetic-bead Luminex assays. In addition, measured sample concentrations were
      higher and recovery was poor (elevated) after hyaluronidase treatment. In the MSD
      4-plex, within-group comparison of the intra-assay CV or concentration was not
      conclusively influenced by SF preparation. However, only hyaluronidase treatment
      resulted in CV<25% for all samples for TNF-alpha. There was no effect on analyte
      concentrations or recovery. Hyaluronidase treatment can improve intra-assay
      precision and assay signal of SF analysis by multiplex immunoassays and should be
      recommended for SF biomarker research, particularly using the Luminex platform.

PMID- 22955211
TI  - Antibody immobilization using pneumatic spray: comparison with the avidin-biotin
      bridge immobilization method.
AB  - The formation of a thin antibody film on a glass surface using pneumatic spray
      was investigated as a potential immobilization technique for capturing pathogenic
      targets. Goat-Escherichia coli O157:H7 IgG films were made by pneumatic spray and
      compared against the avidin-biotin bridge immobilized films by assaying with
      green fluorescent protein (GFP) transformed E. coli O157:H7 cells and fluorescent
      reporter antibodies. Functionality, stability, and immobilization of the films
      were tested. The pneumatic spray films had lower fluorescence intensity values
      than the avidin-biotin bridge films but resulted in similar detection for E. coli
      O157:H7 at 10(5)-10(7)cells/ml sample concentrations with no detection of non-E.
      coli O157:H7 strains. Both methods also resulted in similar percent capture
      efficiencies. The results demonstrated that immobilization of antibody via
      pneumatic spray did not render the antibody non-functional and produced stable
      antibody films. The amount of time necessary for immobilization of the antibody
      was reduced significantly from 24h for the avidin-biotin bridge to 7 min using
      the pneumatic spray technique, with additional benefits of greatly reduced use of
      materials and chemicals. The pneumatic spray technique promises to be an
      alternative for the immobilization of antibodies on glass slides for capturing
      pathogenic targets and use in biosensor type devices.

PMID- 22955213
TI  - From the editor.

PMID- 22955212
TI  - Optimization and qualification of an 8-color intracellular cytokine staining
      assay for quantifying T cell responses in rhesus macaques for pre-clinical
      vaccine studies.
AB  - Vaccination and SIV challenge of macaque species is the best animal model for
      evaluating candidate HIV vaccines in pre-clinical studies. As such, robust assays
      optimized for use in nonhuman primates are necessary for reliable ex vivo
      measurement of immune responses and identification of potential immune correlates
      of protection. We optimized and qualified an 8-color intracellular cytokine
      staining assay for the measurement of IFNgamma, IL-2, and TNF from viable CD4 and
      CD8 T cells from cryopreserved rhesus macaque PBMC stimulated with peptides.
      After optimization, five laboratories tested assay performance using the same
      reagents and PBMC samples; similar results were obtained despite the use of flow
      cytometers with different configurations. The 8-color assay was then subjected to
      a pre-qualification study to quantify specificity and precision. These data were
      used to set positivity thresholds and to design the qualification protocol. Upon
      completion of the qualification study, the assay was shown to be highly
      reproducible with low inter-aliquot, inter-day, and inter-operator variability
      according to the qualification criteria with an overall variability of 20-40% for
      each outcome measurement. Thus, the 8-color ICS assay was formally qualified
      according to the ICH guidelines Q2 (R1) for specificity and precision indicating
      that it is considered a standardized/robust assay acceptable for use in pre
      clinical trial immunogenicity testing.

PMID- 22955214
TI  - Guest editorial.

PMID- 22955215
TI  - The ascension health experience: maximizing the chief nursing officer role in a
      large, multihospital system to advance patient care quality and safety.
AB  - Ascension Health is the largest Catholic and nonprofit health system in the
      United States, encompassing 70 acute care hospitals organized into 34 health
      ministries. Consistent with its distributed leadership model, Ascension Health
      has created a Chief Nursing Officer (CNO) Advisory Council to provide strategic
      direction and thought leadership on major system-level initiatives that impact
      quality, safety, operational performance, nursing leadership, and patient care
      delivery. The council fosters systemwide CNO engagement and dialogue through a
      unique structure of regional CNO work teams called "pods," each of which is
      chaired by a member of the council. This communication structure has facilitated
      consensus on major system initiatives at Ascension Health related to clinical
      goals, patient safety, nursing leadership, and systemwide capital investments.
      This article describes the history, structure, goals, processes, and successes of
      the CNO Advisory Council shared governance model.

PMID- 22955216
TI  - The American Organization of Nurse Executives System CNE task force: a work in
      progress.
AB  - Health care is a complex industry, consequently requiring a diverse group of
      health care executives leading initiatives for efficiency and effectiveness in
      patient care delivery. Value-based purchasing and pay for performance are at the
      top of the list for indicators of success, and many hospitals are merging into
      health care systems. The role of the system chief nurse executive is an evolving
      role to lead health care systems in clinical, operational, patient safety, and
      patient satisfaction processes and outcomes. The American Organization of Nurse
      Executives, being the voice for nursing leadership, convened a group of system
      chief nurse executives to address the role, function, and competencies needed for
      this significant and emerging role in health care. This article describes the
      role statement and system chief nurse executive competencies needed for success
      in the role. In addition, the next steps for addressing the needs of this group
      will be outlined in this article.

PMID- 22955217
TI  - The system chief nurse executive role: sign of the changing times?
AB  - As the health care system landscape continues to evolve toward more integrated
      care, a trend toward consolidation of hospitals into larger systems continues.
      The systems are more than the traditional hospital-centric structures, as acute
      care becomes just one component to a larger system that includes ambulatory care,
      acute and post-acute care, chronic disease and end-of-life management, and all
      structures in between. To provide leadership in these new models, there have been
      an increasing number of system chief nurse executives hired both to facilitate
      the integration of care and to align and standardize nursing practice across the
      continuum. By definition, the role of the system chief nurse executive differs
      from that of the entity chief nursing officer. A crosswalk is presented that
      describes the differences between the roles and reflects on the implication for
      system chief nurse executives during our changing times.

PMID- 22955218
TI  - Opportunities and strategies in contemporary health system executive leadership.
AB  - The contemporary health care environment presents opportunities for nurse
      executive leadership that is patient and family centered, satisfying to
      professional nurses and their colleagues, and results in safe quality care that
      is fiscally responsible and evidence based. This article focuses on the strategic
      areas of systemness, people, performance, and innovation and offers strategies
      and tactics to help move nursing in integrated delivery systems from important
      entity-based services to a system approach where the nursing leadership team and
      entity chief nursing officers are recognized as major contributors to system
      success.

PMID- 22955219
TI  - Model of care transformation: a health care system CNE's journey.
AB  - In 2001, the Institute of Medicine released the report "Crossing the Quality
      Chasm: A New Health System for the 21st Century." The report criticizes our
      health care system and argues that we are failing to provide Americans with the
      high-quality and affordable health care they deserve and need. While incremental
      progress has been made, we continue to strive for improved care quality, and our
      rising costs are potentially catastrophic. Consistent with the Institute of
      Medicine report, and its reputation for innovation, Inova Health System
      identified care model transformation as a system priority. Given that the
      organization is replacing its electronic health record and introducing advanced
      analytic capabilities, the opportunity to transform the model of care in tandem
      with core clinical platform enhancement was a compelling reason to move forward.

PMID- 22955220
TI  - New clinical executive models: one system's approach to chief nursing officer
      chief medical officer co-leadership.
AB  - The current complex and rapidly changing health care environment calls for new
      approaches to leadership, particularly for clinical leaders as they assume
      greater responsibility for identifying and managing the clinical leverage points
      that create value. The chief nursing officer-chief medical officer dyad as a co
      leadership model is one such approach. Catholic Health Initiatives is a large,
      complex health care system in the United States that has embraced this
      partnership-based model. On the basis of Catholic Health Initiatives experience,
      attention to the design of such partnerships is critical for their success, and a
      number of guiding principles have emerged. In addition, leadership development
      interventions, with attention to both the individual and the partnership, can
      play a critical role in supporting the evolution of strong and effective clinical
      dyads.

PMID- 22955221
TI  - Alignment of the system's chief nursing officer: staff or direct line structure?
AB  - The role of the system chief nursing officer nationally and internationally has
      been traditionally structured as a staff model, a direct line model, or a hybrid
      that includes parts of each model. The choice of structure should be made after a
      thorough investigation of what outcomes the system wants this position to
      accomplish, developing the appropriate structure to achieve these outcomes, and
      then engaging a chief nursing officer with the skills indicated by the type of
      structure chosen. This article describes these 3 structures and the support
      infrastructure necessary for each model.

PMID- 22955223
TI  - The nursing quality partnership: building a health system approach to improving
      care in community hospitals using principles of the magnet program of excellence.
AB  - Review of the Magnet Recognition Program journey related to the partnership
      between nursing and quality in building a comprehensive, results-driven quality
      and safety program in a 5 hospital community system in suburban Philadelphia over
      a 5-year period (2006-2011).

PMID- 22955222
TI  - Nursing research across a large health care system: sparking nurses' clinical
      inquiry.
AB  - In our journey to achieve Magnet designation, we sought to increase staff nurses'
      research participation and teach them about the research process by conducting a
      corporate-wide study, a blind taste test, using potato chips. PURPOSE: To compare
      3 varieties of the same-brand potato chips for overall preference and perception
      of healthiness. We hypothesized that the potato chip the nurses liked the best
      would not be the chip they perceived as the healthiest. METHODS: For this
      institutional review board-approved study, nurses were recruited via (1) randomly
      selected units and (2) a convenience sample during cafeteria lunch hours. After
      informed consent was obtained, nurses rated each potato chip in a blinded manner,
      based on appearance, crispiness, flavor, saltiness, and greasiness. They
      indicated which potato chip they perceived to be the healthiest and which they
      preferred overall, and they completed an anonymous demographic questionnaire.
      RESULTS: A total of 263 nurses participated, with 78% being staff nurses. Regular
      (full fat) was most preferred (37.6%), whereas fat free was least preferred (16%)
      and also considered the healthiest (45.2%) (P < .0001). CONCLUSIONS: Nurses
      preferred the regular chip and chose the fat-free chip as the healthiest, proving
      our hypothesis that the preferred chip would not be considered the healthiest.
      IMPLICATIONS: This study was easy, feasible, and helped promote systemwide
      nursing research.

PMID- 22955224
TI  - An integrated system's nursing shared governance model: a system chief nursing
      officer's synergistic vehicle for leading a complex health care system.
AB  - Seton Nursing reengineered previous models of care and leadership to accommodate
      rapid growth of its health care system from individual acute care sites to a
      health care system with consistent quality and standardization of like units
      across the system. Shared governance promotes collaboration with shared decision
      making and accountability; however, the role and methods of a system chief
      nursing officer to connect shared governance across a new system has not been
      previously described. A system chief nursing officer can significantly influence
      and guide the nursing strategic direction at all the health care system-related
      facilities by utilizing a single, systemwide nursing shared governance structure.
      Using this structure provides a venue to maximize the influence of a
      transformational leader and creates efficiencies in workforce development,
      resource management, best practice identification, and spread of initiatives and
      improvements to adapt to an ever-changing health care landscape. This is the
      story of one such system chief nursing officer.

PMID- 22955225
TI  - Strategic workforce planning for a multihospital, integrated delivery system.
AB  - Banner Health has long recognized the need to anticipate, beyond the immediate
      operational realities or even the annual budgeting projection exercises, the
      necessary workforce needs of the future. Thus, in 2011, Banner implemented a
      workforce planning model that included structures, processes, and tools for
      predicting workforce needs, with particular focus on identified critical
      systemwide practice areas. The model represents the incorporation of labor
      management tools and processes with more strategic, broad-view, long-term
      assessment and planning mechanisms. The sequential tying of the workforce
      planning lifecycle with the organization's strategy and financial planning
      process supports alignment of goals, objectives, and resource allocation.
      Collaboration among strategy, finance, human resources, and operations has
      provided us with the ability to identify critical position groups based on 3-year
      strategic priorities. By engaging leaders from across the organization, focusing
      on activities at facility, regional, and system levels, and building in
      mechanisms for accountability, we are now engaged in continuous evaluations of
      our delivery models, the competencies and preparations necessary for the staff to
      effectively function within those delivery models, and developing and
      implementing action plans designed to ensure adequate numbers of the staff whose
      competencies will be suited to the work expected of them.

PMID- 22955226
TI  - Perceptions of shared governance among nurses at a midwestern hospital.
AB  - Shared governance is a model of nursing leadership that drives practice. The
      purpose of this project was to determine whether nursing education, work
      experience, certification, employment position, setting (inpatient/ambulatory),
      participation in shared governance, and age were related and predictive of scores
      on the Index of Professional Nursing Governance (IPNG). The significance was to
      provide a basis on which to enhance a nursing shared governance model resulting
      in enhanced patient care. This prospective, cross-sectional study included nurses
      in any type of nursing role and with any level of educational preparation. An
      analysis of variance was employed to identify strength of relationships among the
      categorical or ordinal variables and regression models for the continuous
      variables. General linear models were used to identify the variables most
      predictive of IPNG scores. Of the 98 participants, most (96%) were women, 58%
      were bachelor's prepared, and 80% were staff nurses. The mean IPNG score was
      186.5. No significant relationships were found among demographic measures and
      IPNG scores. A reported role in shared governance, when combined with work
      setting (inpatient or ambulatory), was predictive of IPNG scores. Nurses who
      worked in the inpatient setting reported higher mean IPNG scores.

PMID- 22955227
TI  - Late calcineurin inhibitor withdrawal prevents progressive left ventricular
      diastolic dysfunction in renal transplant recipients.
AB  - BACKGROUND: Calcineurin inhibitor (CNI)-based therapy is associated with adverse
      cardiovascular effects. We examined the effects of late CNI or mycophenolate
      mofetil (MMF) withdrawal on echocardiographic parameters. METHODS: This study was
      conducted as a substudy of a randomized trial in stable renal transplant
      recipients who were on a triple CNI-based regimen with prednisone and MMF that
      evaluated late concentration-controlled withdrawal of CNI or MMF on renal
      function. A total of 108 patients (age, 52.3+/-11.5 years; 67% male; at a median
      of 2.0 years post-transplantation, (interquartile range 1.3-3.3 years); estimated
      glomerular filtration rate, 57+/-16 mL/min/1.73 m; 66% on cyclosporine and 34% on
      tacrolimus) entered the cardiovascular substudy examining echocardiographic
      parameters at baseline and 2 years after randomization. In all patients,
      traditional cardiovascular risk factors were treated according to predefined
      targets. RESULTS: Late CNI withdrawal prevented progressive development of left
      ventricular (LV) diastolic dysfunction, as assessed by markers of LV diastolic
      function (mitral deceleration time and mitral annular e' velocity). Conversely,
      in the MMF-withdrawal group, the left atrial volume index (an indicator of
      chronic LV diastolic dysfunction) was significantly increased at 2 years (from
      24.1+/-6.7 to 27.0+/-7.0 mL/m, P<0.05). In addition, CNI withdrawal resulted in a
      higher proportion of patients achieving the predefined blood pressure targets
      (<130/85 mm Hg: 41.5% vs. 12.7%, P=0.001) at 2 years while requiring less
      antihypertensive drugs. Changes in the left atrial volume index were
      significantly associated with treatment arm (P=0.03) and changes in systolic
      (P=0.005) and diastolic (P=0.005) blood pressure. CONCLUSIONS: Late CNI
      withdrawal, from a triple-drug regimen in stable renal transplant recipients,
      prevented progressive deterioration of LV diastolic function and facilitated
      better blood pressure control.

PMID- 22955228
TI  - Independent of nephrectomy, weaning immunosuppression leads to late sensitization
      after kidney transplant failure.
AB  - BACKGROUND: Patients returning to dialysis therapy after renal transplant failure
      have a high rate of human leukocyte antigen antibody sensitization, and
      sensitization has been linked to allograft nephrectomy. We hypothesized that
      nephrectomy for cause is a consequence of weaning immunosuppression and that
      weaning leads to sensitization even in the absence of nephrectomy. METHODS: We
      examined outcomes in 300 consecutive patients with kidney allograft failure and
      survival of more than 30 days after failure. We analyzed a subset of 119 patients
      with a low panel reactive antibody (PRA) before transplantation and follow-up PRA
      testing at 6 to 24 months after failure (late PRA). RESULTS: By late PRA testing,
      56% of patients were highly sensitized (class I or II PRA >=80%). On multivariate
      analysis controlling for human leukocyte antigen matching, allograft nephrectomy,
      and other variables, weaning of immunosuppression predicted high sensitization
      (odds ratio, 14.34; P=0.004). In a subset of patients, the percentage of those
      who were highly sensitized increased from 21% at the time of failure on
      immunosuppressive therapy to 68% by late PRA after weaning (P<0.001). Conversely,
      patients who maintained immunosuppression showed minimal sensitization after
      failure. Transplant nephrectomy was required in 41% of patients who weaned
      immunosuppression versus 0% of the 24 patients who maintained immunosuppression
      with calcineurin inhibitor therapy after failure (P<0.001). CONCLUSIONS: Weaning
      immunosuppression was a triggering event leading to late rejection and allograft
      nephrectomy and was an independent predictor of alloantibody sensitization after
      kidney allograft failure.

PMID- 22955230
TI  - Endoscopic evaluation of small intestine transplant grafts.
AB  - BACKGROUND: The management of small bowel transplantation is unique because signs
      of rejection can be obtained visually by endoscopy. The aim of this study was to
      evaluate the accuracy of endoscopic appearance in assessing histologic evidence
      of acute cellular rejection (ACR). METHODS: Endoscopies were performed in 66
      asymptomatic "surveillance" small bowel transplant recipients and 71 symptomatic
      recipients from a single center. For surveillance patients, 125 ileoscopies were
      performed to collect 590 biopsies, and for the symptomatic group, 229 ileoscopies
      and jejunoscopies were conducted to obtain 434 biopsies. RESULTS: The sensitivity
      and specificity of endoscopic visualization in detecting ACR was 50% and 91.5%
      for the surveillance group and 43% and 67% for the symptomatic patients. In
      surveillance, visual impression alone would have missed three cases of moderate
      and no cases of severe ACR, whereas in the symptomatic group, visual inspection
      alone would have missed 20 cases of moderate ACR, and findings from visual
      inspection of the chimney were normal in 55% of cases with proximal ACR. However,
      chimney biopsy was generally representative of biopsy findings in the proximal
      graft but would have missed moderate to severe rejection in three patients (1%).
      In a subset of 23 endoscopies, zoom endoscopy did not improve visual
      discrimination. The only complication was a biopsy-related non-life-threatening
      bleed. CONCLUSIONS: In symptomatic patients, visual inspection detected all cases
      of severe rejection but would have missed patients with early readily treatable
      rejection and thus making biopsy mandatory in clinical practice. Our results
      support the current practice of ileoscopic biopsy alone for graft surveillance in
      asymptomatic patients.

PMID- 22955229
TI  - SOD mimetic improves the function, growth, and survival of small-size liver
      grafts after transplantation in rats.
AB  - BACKGROUND: Small-for-size syndrome (SFSS) may occur when graft volume is less
      than 45% of the standard liver volume, and it manifests as retarded growth and
      failure of the grafts and more mortality. However, its pathogenesis is poorly
      understood, and few effective interventions have been attempted. AIMS: The
      present study aimed to delineate the critical role of oxidant stress in SFSS and
      protective effects of a superoxide dismutase mimetic, Mn(III)tetrakis(4-benzoic
      acid)porphyrin chloride (MnTBAP), on graft function, growth, and survival in the
      recipient rats. METHODS: Small size graft liver transplantation (SSGLT) was
      performed to determine the survival, graft injury, and growth. MnTBAP was
      administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS: Serum alanine
      aminotransferase levels were sustained higher in SSGLT recipients, which were
      correlated with an increased apoptotic cell count and hepatocellular necrosis in
      liver sections. Malondialdehyde content, gene expression of tumor necrosis factor
      alpha and interleukin 1beta, and DNA binding activity of nuclear factor-kappaB in
      the grafts were increased significantly in SSGLT recipients compared with sham
      operated controls. Both phosphorylated p38 mitogen-activated protein kinase and
      nuclear c-Jun were increased in SSGLT. All these changes were strikingly reversed
      by the administration of MnTBAP, with an increase in serum superoxide dismutase
      activity. Moreover, in situ bromodeoxyuridine incorporation demonstrated that
      graft regeneration was much more profound in the SSGLT+MnTBAP group than in the
      SSGLT group. Finally, the survival of recipients with MnTBAP treatments was
      significantly improved. CONCLUSIONS: Enhanced oxidant stress with activation of
      the p38/c-Jun/nuclear factor-kappaB signaling pathway contributes to SFSS
      associated graft failure, retarded graft growth, and poor survival. MnTBAP
      effectively reversed the pathologic changes in SFSS-associated graft failure.

PMID- 22955231
TI  - A small predatory core genome in the divergent marine Bacteriovorax marinus SJ
      and the terrestrial Bdellovibrio bacteriovorus.
AB  - Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a
      marine environment. The genome sequence of this strain provides an interesting
      contrast to that of the terrestrial predatory bacterium Bdellovibrio
      bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were
      originally designated as members of the genus Bdellovibrio but subsequently were
      re-assigned to a new genus and family based on genetic and phenotypic
      differences. B. marinus attaches to gram-negative bacteria, penetrates through
      the cell wall to form a bdelloplast, in which it replicates, as shown using
      microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products
      with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500
      nt in length were completely unique with no significant matches in the databases.
      As expected, Bacteriovorax shares several characteristic loci with the other
      delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio
      that is not conserved among other delta-proteobacteria such as Myxobacteria
      (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo
      bacteria and Geobacter species was identified. These 291 gene orthologues common
      to both Bacteriovorax and Bdellovibrio may be the key indicators of host
      interaction predatory-specific processes required for prey entry. The locus from
      Bdellovibrio bacteriovorus is implicated in the switch from predatory to
      prey/host-independent growth. Although the locus is conserved in B. marinus, the
      sequence has only limited similarity. The results of this study advance
      understanding of both the similarities and differences between Bdellovibrio and
      Bacteriovorax and confirm the distant relationship between the two and their
      separation into different families.

PMID- 22955232
TI  - Organic carbon transformations in high-Arctic peat soils: key functions and
      microorganisms.
AB  - A substantial part of the Earths' soil organic carbon (SOC) is stored in Arctic
      permafrost peatlands, which represent large potential sources for increased
      emissions of the greenhouse gases CH(4) and CO(2) in a warming climate. The
      microbial communities and their genetic repertoire involved in the breakdown and
      mineralisation of SOC in these soils are, however, poorly understood. In this
      study, we applied a combined metagenomic and metatranscriptomic approach on two
      Arctic peat soils to investigate the identity and the gene pool of the microbiota
      driving the SOC degradation in the seasonally thawed active layers. A large and
      diverse set of genes encoding plant polymer-degrading enzymes was found,
      comparable to microbiotas from temperate and subtropical soils. This indicates
      that the metabolic potential for SOC degradation in Arctic peat is not different
      from that of other climatic zones. The majority of these genes were assigned to
      three bacterial phyla, Actinobacteria, Verrucomicrobia and Bacteroidetes.
      Anaerobic metabolic pathways and the fraction of methanogenic archaea increased
      with peat depth, evident for a gradual transition from aerobic to anaerobic
      lifestyles. A population of CH(4)-oxidising bacteria closely related to
      Methylobacter tundripaludum was the dominating active group of methanotrophs.
      Based on the in-depth characterisation of the microbes and their genes, we
      conclude that these Arctic peat soils will turn into CO(2) sources owing to
      increased active layer depth and prolonged growing season. However, the extent of
      future CH(4) emissions will critically depend on the response of the
      methanotrophic bacteria.

PMID- 22955233
TI  - Hybrid 18F-FDG PET/CT of colonic anastomosis. A possibility to detect anastomotic
      leakage?
AB  - 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a known method
      to diagnose inflammatory processes and thus may be a promising imaging technique
      to detect anastomotic bowel leak. The aim of this study was to assess
      postoperative FDG uptake in colorectal anastomosis in patients without suspicion
      of active infection or anastomotic leakage. PATIENTS, METHODS: Design of a
      prospective observational pilot study in order to assess normal FDG uptake in the
      patient anastomosis after colorectal surgery. Patients that underwent colorectal
      surgery with primary anastomosis received FDG-PET of the abdomen, 2-6 days
      postoperatively. RESULTS: 35 patients met the inclusion criteria. Three patients
      were not scanned for various reasons. Of the remaining 32 patients, one
      demonstrated an increased uptake of FDG at the site of the anastomosis. In the
      other 31 patients FDG uptake was negligible (n = 17) or scored as physiological
      (n = 14). None of the scanned patients developed a clinical relevant anastomotic
      leakage within the first 30 days after surgery. CONCLUSION: The present study
      shows that FDG uptake in colorectal anastomosis remains low within the first six
      days after surgery in patients without anastomotic leakage. Therefore, FDG-PET
      might be useful to investigate further as a tool to detect anastomotic leakage in
      an the early postoperative phase.

PMID- 22955234
TI  - Pseudopeptidic ligands: exploring the self-assembly of isophthaloylbisglycine
      (H2IBG) and divalent metal ions.
AB  - We present a systematic study of the complexation of the new pseudopeptidic
      ligand isophthaloylbisglycine (H(2)IBG) with divalent metal ions of varying ionic
      radius. This work represents the initial employment of H(2)IBG in the
      coordination chemistry of alkaline earth, 3d transition, Zn(II) and Cd(II) metal
      elements. Infrared, NMR, thermal, magnetic, adsorption and theoretical studies of
      these compounds are also discussed.

PMID- 22955235
TI  - Choice ... it's deja vu all over.

PMID- 22955236
TI  - Associations between working memory, health literacy, and recall of the signs of
      stroke among older adults.
AB  - Stroke remains a major cause of mortality and disability among older adults.
      Although early treatment after stroke is known to reduce both mortality and
      disability, the first step in seeking early treatment is dependent on the rapid
      recognition of the signs of stroke. Recall of the signs of stroke may be
      dependent on factors that exist before the stroke itself. Although it is known
      that both working memory and health literacy decline with advancing age, these
      factors have not been thoroughly examined with respect to recall of the signs of
      stroke. Therefore, the purpose of the current study was to investigate
      associations between working memory, health literacy, and recall of the signs of
      stroke among older adults. Community dwelling older adults (>=65 years of age)
      were recruited from two senior centers. Fifty-six participants meeting inclusion
      criteria provided demographic and health information and were asked to read a
      public service brochure listing the five warning signs of stroke. Working memory
      was then assessed using the Wechsler Adult Intelligence Scale 3rd Edition Working
      Memory Index. Health literacy was assessed by the Short Test of Functional Health
      Literacy in Adults. Participants' recall of the five warning signs of stroke was
      evaluated. The mean age was 80.4 years. The mean number of the signs of stroke
      recalled was 2.9 +/- 1.33. Working memory and health literacy were positively
      correlated with recall of the signs of stroke (r = .38, p < 0.01; r = .44, p <
      0.01). In a simultaneous regression, only health literacy remained a significant
      predictor of recall. There was no statistically significant interaction between
      working memory and health literacy. Findings from this study indicate that
      working memory and health literacy were associated with successful recall of the
      warning signs of stroke in older adults. Further studies are needed to determine
      if programs that include cognitive and literacy assessments could identify older
      adults who need additional support to learn and recall the signs of stroke.

PMID- 22955237
TI  - Evidence supporting the incorporation of the dietary approaches to stop
      hypertension (DASH) eating pattern into stroke self-management programs: a
      review.
AB  - Stroke is a major source of mortality and morbidity in the United States.
      Nutrition can impact factors that increase the risk of stroke such as
      hypertension, obesity, elevated blood lipids, and diabetes. The Michael E.
      DeBakey Veteran's Affairs Medical Center (MEDVAMC) has developed the Self
      Management to Prevent (STOP) Stroke Program to help veterans at risk for stroke
      and stroke recurrence. Patient initial feedback indicated a desire for more in
      depth nutrition education in the STOP Stroke program. To address the needs of
      veterans living some distance from the MEDVAMC, a video teleconference program
      was developed and modified to include the Dietary Approaches to Stop Hypertension
      (DASH) diet nutrition concepts. This literature review summarizes the scientific
      evidence used to support the incorporation of the DASH eating pattern into the
      MEDVAMC STOP Stroke video teleconference program. Institutions can use this
      review to support development of similar nutrition education components for other
      stroke risk management programs.

PMID- 22955239
TI  - Functional capacity of patients in the early period after the embolization of
      cerebrovascular malformations: preliminary findings.
AB  - Research into outcomes of endovascular intervention for cerebral blood vessel
      malformations has previously focused on the clinical picture of the disease,
      death rate, comparison of surgical methods, and the most common postoperative and
      postbleeding complications. From the nursing standpoint, the crucial elements in
      assessing postoperative patients are functional outcome defining patients'
      ability to function in life and recognition of impairments in which patients will
      be dependent on the nursing staff. The aim of the study was to assess functional
      capacity of patients before and after the embolization of cerebral blood vessel
      malformations in the aspect of nursing care. The study included 38 patients after
      embolization of cerebral blood vessels. The assessment of their condition using
      the Functional Capacity Scale was performed twice: before and after the surgical
      procedure. The research shows that on the day of admission to hospital, patients
      had greatest difficulty performing hygienic activities (p < .0001), satisfying
      physiological needs (p < .0001), and consuming their meals (p < .004). Headache
      (p < .002) and poor psychological state (p < .0001) manifesting itself through
      mild depression constituted other serious problems. After the surgery, vast
      majority of patients were independent in terms of self-care (p <= .03). Headache
      occurred in the case of 21% of patients, and psychological state improved in 34%
      of patients, which shows that there is a major demand for care in this sphere.

PMID- 22955240
TI  - Nursing care of patients with disorders of consciousness.
AB  - Management of severely brain-injured patients constitutes a social, economical,
      and ethical dilemma as well as a real challenge for the medical staff, as it
      requires specific expertise. The aim of this article is to explore the aspects of
      nursing care in patients recovering from coma such as difficulty of diagnosis,
      residual perception, clinical assessment, care and management, and communication
      with the patient and the family. The nursing care of patients with disorder of
      consciousness must be particular and specific for various reasons such as the
      difficult diagnosis, the problem of unconsciousness or lack of demonstration of
      consciousness, extremely complex clinical assessment, daily management with total
      dependence, communication with patients that requires special attention and
      training by health professionals, and communication with the family of these
      patients that requires more sensitivity and full involvement by the team.

PMID- 22955241
TI  - Coping and adaptation in adults living with spinal cord injury.
AB  - Biopsychosocial adaptation remains a multifaceted challenge for individuals with
      spinal cord injury, their families, and healthcare providers alike. The
      development of frequent medical complications necessitating healthcare
      interventions is an ongoing, debilitating, and costly problem for those living
      with spinal cord injuries. Although several demographic variables have been
      correlated with positive adaptation in individuals with spinal cord injury, the
      research outcome data present limitations in understanding and facilitating which
      coping techniques work best to augment biopsychosocial adaptation in this
      population. Coping facilitates adaptation and adjustment to stress and can help
      to increase quality of life in people living with spinal cord injury and reduce
      common complications. The purpose of this study was to determine the extent to
      which sociodemographic characteristics and hardiness explain coping in 243 adults
      living with a spinal cord injury. In addition, this study examined which
      predictors of coping explain biopsychosocial adaptation. A descriptive
      explanatory design was utilized. Standardized instruments were administered
      nationally to assess hardiness, coping, and physiological and psychosocial
      adaptation. Canonical correlation and multiple regression analyses indicated that
      less educated, less hardy, and recently injured participants were more likely to
      use escape-avoidance coping and less likely to use social support, problem
      solving, and positive reappraisal coping behaviors (p < .05). Individuals with
      paraplegia had a higher level of functional ability, spent less time in
      rehabilitation, had a greater sense of control, and experienced less frequent
      complications. The control dimension of hardiness was the only dimension that
      significantly related to biopsychosocial adaptation within this sample.

PMID- 22955242
TI  - Neuroendovascular treatments/procedures: are they efficacious and have they
      improved patient outcomes poststroke?
AB  - Stroke is the second most common cause of death in women and African Americans,
      the fourth leading cause of death in Caucasians, and the fifth leading cause of
      death in men in the United States (). In addition, stroke costs the nation
      greater than $57 billion dollars annually through its direct and indirect costs.
      For example, in the year 2009 alone, the estimated expenditure on the cost of
      stroke for hospitalization, rehabilitation, and institutionalization was $68.9
      billion. Fortunately, there are many treatment strategies available to
      individuals who had a stroke if they meet certain clinical and time criteria as
      well as being geographically located in a region where these treatments are
      available, such as nationally certified stroke centers. Specifically, intravenous
      and intra-arterial recombinant tissue plasminogen activator (rtPA) and mechanical
      thrombolysis are used for acute ischemic stroke, whereas treatments for acute
      hemorrhagic stroke resulting from subarachnoid hemorrhage secondary to ruptured
      cerebral aneurysm include both endovascular coiling as well as surgical clipping.
      However, patient outcomes from some of these treatments are controversial. First,
      it appears that, although revascularization post mechanical thrombectomy has high
      success rates, patient clinical and neurological outcomes as evidenced by low
      modified Rankin Scale scores are not as favorable when compared with intravenous
      or intra-arterial thombolysis. However, endovascular coiling for ruptured
      cerebral aneurysms resulting in subarachnoid hemorrhage appears to be superior to
      aneurysm clipping in both clinical and neurological outcomes. Future studies need
      to focus on making subject pools more homogeneous as well as using standardized
      outcome measures to facilitate external validation of their results.

PMID- 22955243
TI  - The educational needs of newly diagnosed stroke patients.
AB  - There is limited research related to perceived educational needs among the newly
      diagnosed first-time stroke population. This descriptive correlational study was
      conducted to determine the perceived importance to learn about specific stroke
      related topics and the degree of satisfaction with stroke education. Seventy-one
      newly diagnosed stroke patients from two metropolitan hospitals received a self
      report Likert-type questionnaire consisting of eight domains related to different
      aspects of stroke education. The questionnaire was distributed 24-72 hours after
      admission to the hospital, upon discharge, and 2 weeks postdischarge. The data
      were analyzed using descriptive statistics, t tests, and repeated measures
      analysis of variance. Medical knowledge and medication treatment were rated the
      most important to learn. Treatment of stroke with herbal or alternative medicine
      and dietary habits were the least important of the eight domains. Overall,
      patients were not satisfied with stroke education.

PMID- 22955244
TI  - Pathogenesis of malaria revisited.
AB  - Plasmodium falciparum malaria claims 1 million lives around the globe every year.
      Parasitemia can reach remarkably high levels. The developing parasite digests
      hemoglobin and converts the waste product to hemozoin alias malaria pigment.
      These processes occur in a vesicular compartment named the digestive vacuole
      (DV). Each parasitized cell releases one DV upon rupture. Myriads of DVs thus
      gain entry into the blood, but whether they trigger pathobiological events has
      never been investigated. We recently discovered that the DV membrane
      simultaneously activates the two major enzyme cascades in blood, complement and
      coagulation. Activation of both is known to occur in patients with severe
      malaria, so discovery of the common trigger has large consequences. The DV
      membrane but not the merozoite has the capacity to spontaneously activate the
      alternative complement and intrinsic clotting pathway. Ejection of merozoites and
      the DV into the bloodstream, therefore, results in selective opsonization and
      phagocytosis of the DV, leaving merozoites free to invade new cells. The DV
      membrane furthermore has the capacity to assemble prothrombinase, the key
      convertase of the intrinsic clotting pathway. The dual capacity of the DV to
      activate both complement and coagulation can be suppressed by low-molecular
      weight dextran sulfate. This agent protects experimental animals from the
      detrimental consequences, resulting from intravenous application of purified DVs.
      Phagocytosis of DVs not only deploys PMN away from merozoites, but also drives
      the cells into a state of functional exhaustion. This may be one reason for the
      enhanced susceptibility of patients with severe malaria toward systemic bacterial
      infections. Together, these findings indicate that the DV may represent a
      hitherto unrecognized, important determinant of parasite pathogenicity.

PMID- 22955245
TI  - Anxiety and smoking cessation outcomes in alcohol-dependent smokers.
AB  - INTRODUCTION: Anxiety-related characteristics, including anxiety sensitivity and
      trait anxiety, are elevated in individuals with alcohol and nicotine dependence
      and associated with greater difficulties with quitting smoking. However, little
      is known about how anxiety-related characteristics are related to smoking
      cessation outcomes in alcohol-dependent smokers. The present study, part of a
      larger smoking cessation clinical trial, examined associations between anxiety
      sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and
      smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. METHODS:
      Participants were enrolled in concurrent alcohol and tobacco treatment as part of
      a substance-abuse intensive outpatient program. Smoking cessation treatment was
      administered in a 3-week cognitive-behavioral format that included 8 weeks of
      open-label nicotine patch treatment. Information on nicotine withdrawal, smoking
      urges, and CO-confirmed smoking consumption rates was collected at baseline, quit
      date, end of behavioral treatment, and at a 1-month follow-up. RESULTS: Higher
      levels of anxiety sensitivity were associated with more smoking urges due to
      anticipation of negative affect relief at quit date. Higher levels of trait
      anxiety were associated with more smoking urges due to positive reinforcement and
      anticipation of relief of negative affect at quit date, as well as more severe
      nicotine withdrawal symptoms at the end of treatment. Levels of anxiety
      sensitivity and trait anxiety were not associated with Cox regression survival
      times to relapse. CONCLUSION: These results indicate that for alcohol-dependent
      smokers, levels of anxiety sensitivity and trait anxiety are important to
      consider in the assessment and treatment of nicotine dependence.

PMID- 22955246
TI  - Osmotic release oral system methylphenidate prevents weight gain during a smoking
      cessation attempt in adults with ADHD.
AB  - BACKGROUND: Adults with attention-deficit/hyperactivity disorder (ADHD) are at
      increased risk for both cigarette smoking and being overweight or obese. Although
      smoking cessation tends to result in weight increase, potentially initiating or
      exacerbating weight problems, adults with ADHD who are treated with osmotic
      release oral system methylphenidate (OROS-MPH) tend to lose weight. It is unclear
      how the use of OROS-MPH during a smoking-cessation attempt might affect the
      typical weight gain that accompanies cessation. METHOD: We examined changes in
      weight and hunger during a smoking-cessation attempt in 215 adults with ADHD who
      completed a multisite, randomized, controlled trial and were randomized to either
      OROS-MPH (n = 107) or placebo (n = 108) (NCT #00253747). Both groups also
      received open-label transdermal nicotine replacement and counseling. RESULTS:
      Participants who received OROS-MPH lost an average of 1.6% of their body weight
      during the 11-week study, whereas those who received placebo gained an average of
      1.3% of their weight (p < .001). Hunger ratings were lower in the OROS-MPH group
      (M = 1.1, SD = 0.8) than in the placebo group (M = 1.6, SD = 0.9; p < .001).
      CONCLUSIONS: The use of OROS-MPH during a smoking-cessation attempt prevents
      weight gain in adults with ADHD who substantially reduce or quit smoking. The
      potential utility of OROS-MPH in individuals with ADHD who are attempting to quit
      smoking and for whom weight gain would be problematic warrants further research.

PMID- 22955247
TI  - Monitoring for postnatal hearing loss using risk factors:  a systematic
      literature review.
AB  - OBJECTIVES: The aim of this study was to investigate whether there was evidence
      based support for targeted surveillance programs using a risk-factor registry to
      detect postnatal hearing loss or whether other programs were available that may
      be more effective than targeted surveillance. Particularly, it addressed
      questions that arose along the targeted surveillance pathway, including: (1) the
      risk factors used to determine a referral, (2) referral frequencies, (3) the
      relationship between risk factors and a postnatal hearing loss, and (4) other
      systems that may be more efficient than the use of risk factors. DESIGN: A
      systematic literature review was completed in peer-reviewed and non-peer-reviewed
      databases. METHODS: Publications were obtained using the databases MEDLINE,
      Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica on
      line, and by inspecting the reference lists of relevant articles and expert
      committee papers. Quality assessment ratings and data extraction were completed
      by the research team. RESULTS: In total, 40 articles met the inclusion criteria
      and were included in this review. The outcomes drawn from these studies were
      inconclusive as they were based on small sample sizes and largely from single
      sites only. With this in mind, from the information obtained: (1) gestational
      age, low-birth weight, toxoplasmosis, other infections, rubella, cytomegalovirus
      (CMV), herpes simplex virus infections, craniofacial anomalies, respirator
      support, and the administration of aminoglycosides were the more commonly
      reported risk factors in programs; (2) referral frequency for monitoring
      appointments was approximately 3%; and (3) CMV, extracorporeal membrane
      oxygenation, congenital diaphragmatic hernia, and persistent pulmonary
      hypertension of the newborn were associated with postnatal hearing loss, whereas,
      preauricular skin tags and ear pits, low-birth weight, and toxoplasmosis were
      not. The review also identified that second-phase universal screening programs,
      CMV screening, and genetic screening should be explored as potential additions or
      alternatives to targeted surveillance using risk factors. CONCLUSIONS: Further
      large-scale, population-based research on available programs for the detection of
      postnatal hearing loss should be conducted to improve present practice and assist
      with the development of evidence-based guidelines for hearing monitoring.

PMID- 22955248
TI  - [Chronic obstructive pulmonary disease : new pharmacotherapeutic options].
AB  - Data about the clinical presentation of chronic obstructive pulmonary disease
      (COPD) have resulted in a new classification of the disease. The degree of
      airflow limitation has been amended by symptoms and exacerbation rate. The
      standard pharmacotherapy of stable COPD is in transition, as fixed combinations
      of long acting beta agonists and long acting anticholinergics are in the late
      stages of clinical development. On this background inhaled corticosteroids will
      need to be re-evaluated. Roflumilast is a recently approved therapeutic option
      that primarily diminishes exacerbation frequency in patients with chronic
      bronchitis and severe airflow obstruction (FEV(1) < 50%). In COPD patients with
      acute exacerbations procalcitonin levels can be used to guide antibiotic therapy.
      Comparable clinical outcomes can be achieved while using significantly less
      amounts of antibiotics.

PMID- 22955249
TI  - Prognostic molecular markers and neoadjuvant therapy response in anthracycline
      treated breast cancer patients.
AB  - BACKGROUND: Identifying biomarkers that can predict the prognosis and treatment
      response is helpful for individualizing breast cancer (BC) therapy. A neoadjuvant
      treatment setting is ideal for testing biomarkers capable of predicting the
      treatment response. This study analyzed the value of immunohistochemical
      biomarkers for predicting pathological complete response (pCR) and prognosis in a
      group of BC patients receiving standardized treatment. PATIENTS AND METHODS: A
      total of 100 BC patients were treated with neoadjuvant chemotherapy (four cycles
      of epirubicin and cyclophosphamide) between 2000 and 2005. Formalin-fixed and
      paraffin-embedded core biopsies were taken before chemotherapy for
      immunohistochemical staining of ER, PgR, HER2, Bcl-2, p53, cyclin D1, CK5/6, CK8,
      CK18, and TOP2A. Patient and tumor characteristics and biomarker scores were used
      to predict pCR and prognosis, using logistic regression and Cox proportional
      hazard models. RESULTS: pCR was achieved in 11 patients and was predicted by the
      established marker Ki-67. In addition, CK5/6 and CK18 improved the prediction
      model and were associated with lower pCR rates. For the prognosis, only the
      established markers nodal status, Ki-67, and PgR predicted overall survival and
      nodal status; Ki-67 and PgR predicted distant disease-free survival. CONCLUSIONS:
      In this small retrospective study, CK5/6 and CK18 appeared to improve prediction
      of pCR in addition to the established markers. CK5/6 may indicate a tumor type
      resembling a basal phenotype that is more resistant to anthracycline-based
      therapy, and CK18 may indicate a luminal subtype that is more resistant to
      chemotherapy. However, these results need to be replicated in larger studies.

PMID- 22955250
TI  - Summer atmospheric polybrominated diphenyl ethers in urban and rural areas of
      northern China.
AB  - High levels of polybrominated diphenyl ethers (PBDEs) have been extensively
      reported in urban areas and at e-waste recycling sites in coastal China. However,
      data are scarce in northern China and are not available in rural areas at all. In
      addition, it is often believed that air concentrations in rural areas are lower
      than those in urban areas without distinguishing rural residential areas and open
      fields. In this study, air samples were collected at 17 sites covering urban and
      rural (residential and open field) areas in northern China using active samplers.
      With BDE-209 dominated in all congeners, the average concentrations of BDE-209
      (41 +/- 72 pg/m(3)) and other 13 PBDEs (16 +/- 12 pg/m(3)) were significantly
      lower than those found in south China, such as in Guangzhou or Hong Kong. On
      average, the total PBDE concentrations at the urban sites were 2.2 and 2.9 times
      of those at the rural residential and field sites, respectively.

PMID- 22955251
TI  - Vaginal vault prolapse following cystectomy: transvaginal reconstruction by mesh
      interposition.
AB  - The present study aims to introduce a transvaginal interposition of polypropylene
      mesh as a reproducible procedure for women with vaginal vault prolapse following
      cystectomy due to bladder carcinoma. No recurrent prolapse occurred in two cases
      16 and 4 months after the operation. With apical fixation of the mesh, vaginal
      length can be maintained. No perioperative complications appeared. Performing the
      technique in a reproducible way seems feasible irrespective of differing
      anatomical conditions.

PMID- 22955252
TI  - Effect of childbirth on pelvic organ support and quality of life: a longitudinal
      cohort study.
AB  - INTRODUCTION AND HYPOTHESIS: Although childbirth is known to be a major risk
      factor for pelvic floor disorders, there is a paucity of prospective, long-term
      data addressing this issue. The aim of our study was to evaluate the changes of
      pelvic organ support, symptoms and quality of life (QOL) after childbirth.
      METHODS: Pelvic organ support was objectively assessed using the Pelvic Organ
      Prolapse Quantification method (POP-Q) and pelvic floor symptoms were
      subjectively evaluated using a validated questionnaire performed in the second
      trimester, 14 weeks, 1 and 5 years after delivery. RESULTS: We recruited 182
      nulliparae and 97 (53.3 %) returned for follow-up at 5 years. POP-Q stage after
      vaginal delivery (VD) worsened at all time points. After caesarean the worsening
      in POP-Q stage was temporary at 14 weeks. Prolapse symptoms worsened at 14 weeks
      (p<0.001) and 1 year (p=0.006) after VD but not at 5 years. No changes in
      prolapse symptoms occurred after caesarean. Significant increase in faecal
      incontinence was observed in both delivery groups 5 years after delivery. For all
      pelvic floor disorder domains there were no significant changes in QOL
      irrespective of mode of delivery, except for worsening in general sexual QOL
      after VD. CONCLUSIONS: Five years after childbirth the stage of prolapse worsened
      after VD but not after caesarean. However, there was no impact on prolapse
      symptoms or QOL. After VD women were more likely to experience a worsening in
      general sex score, but no other difference in QOL measures.

PMID- 22955253
TI  - Sustained effectiveness of percutaneous tibial nerve stimulation for overactive
      bladder syndrome: 2-year follow-up of positive responders.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to describe effectiveness
      and safety of percutaneous tibial nerve stimulation (PTNS) at 2 years in women
      with overactive bladder (OAB) syndrome unresponsive to pharmacotherapy. METHODS:
      Of 30 women who had initial positive response to PTNS, 23 continued to receive
      maintenance treatment and were reassessed at 2 years using bladder symptom
      diaries and the Incontinence Impact Questionnaire (IIQ-7). They were also
      questioned on acceptability and any adverse effects of long-term peripheral
      neuromodulative treatment. RESULTS: Data from 23 women were available and 7 had
      been lost to follow-up. With maintenance treatment, the median nocturnal
      frequency at 2 years had decreased by 57 % (3.5 to 1.5 times/night), while the
      median IIQ-7 had reduced from 30.4 to 21.5 (both p<0.01) compared to pre
      treatment baseline. Median nocturnal frequency and IIQ-7 scores at 2 years were
      comparable to those documented after initial response to treatment at 6 weeks,
      suggesting that maintenance therapy continued to suppress OAB symptoms. Daytime
      frequency and daily urgency incontinence episodes at 2 years were statistically
      similar to those documented at 6 weeks and remained lower than pre-treatment
      baseline (6.5 vs 11.8 and 2.0 vs 3.5, respectively, p<0.05). The women received a
      median of 8.42 treatments per year and the median length between treatments was
      64.3 days. Apart from hypaesthesia in the toe of one responder lasting for 4
      months, there were no reported side effects. CONCLUSIONS: Women receiving PTNS
      for intractable OAB syndrome reported significant symptom relief at 2 years. This
      remains a safe mode of second-line treatment with excellent durability.

PMID- 22955254
TI  - Small-bowel obstruction and bladder injury due to retropubic sling malposition in
      the peritoneal cavity.
AB  - We report a case of small-bowel obstruction caused by an internal hernia produced
      by the presence of an intraperitoneal sling mesh. A woman with a history of
      multiple abdominal surgeries was referred from another center after a sling
      procedure. On the fifth day after surgery, she developed small-bowel obstruction.
      Exploratory laparotomy showed the distal ileum compressed between the visceral
      peritoneum of the bladder and a loop mesh sling. The segment of ileum was
      repositioned into the peritoneal cavity and the sling segment was resected. In
      cases of small-bowel obstructions after a mesh surgery, one must be aware of the
      possibility of bowel entrapment and that the mere presence of intraperitoneal
      tape can trigger the obstruction. 

PMID- 22955255
TI  - Delivering instilled hydrophobic drug to the bladder by a cationic nanoparticle
      and thermo-sensitive hydrogel composite system.
AB  - Some bladder disease therapies can benefit from intravesical drug delivery, which
      involves direct instillation of drug into the bladder via a catheter, to attain
      high local concentrations of the drug with minimal systemic effects. Deguelin is
      a potential anticancer agent, however, its poor water solubility and
      neurotoxicity restrict its clinical application. To address these challenges, we
      investigated the promising application of deguelin in the intravesical therapy of
      bladder cancer by designing a novel intravesical drug delivery system for
      deguelin. It was found that deguelin could efficiently kill bladder cancer cells
      and inhibit angiogenesis. Intravesically administrated deguelin had better
      tolerance than systemically applied deguelin. Encapsulation of deguelin in
      cationic DOTAP and monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)
      (MPEG-PCL) hybrid nanoparticles (DMP) created the deguelin loaded DMP
      nanoparticles (D/DMP). They had a mean particle size of 35 nm and zeta potential
      of 21 mV, rendering deguelin completely dispersible in aqueous media.
      Encapsulation of deguelin in cationic DMP nanoparticles enhanced the anticancer
      activity of deguelin in vitro. In addition, D/DMP nanoparticles were incorporated
      into a thermo-sensitive Pluronic F127 hydrogel, forming a novel D/DMP-F system,
      which remained in a flowing liquid state at lower than 25  degrees C, but
      underwent gelation at higher temperatures. The DMP nanoparticles in the F127
      hydrogel system (DMP-F) could significantly extend the hydrophobic drug residence
      time and increase the drug concentration within the bladder. These results
      suggested that DMP-F was a good intravesical drug delivery system and D/DMP-F may
      have promising applications in intravesical therapy of bladder cancer.

PMID- 22955256
TI  - Elder abuse: screening, intervention, and prevention.

PMID- 22955257
TI  - Population pharmacokinetics of farletuzumab, a humanized monoclonal antibody
      against folate receptor alpha, in epithelial ovarian cancer.
AB  - PURPOSE: The purpose of this analysis was to develop a population pharmacokinetic
      model for farletuzumab, a humanized immunoglobulin (Ig)G(1) monoclonal antibody
      (mAb) to the folate receptor alpha, which is a receptor over-expressed in ovarian
      cancer, but largely absent from normal tissue. METHODS: In total, 2,472 samples
      were included in the building of the pharmacokinetic model. Farletuzumab 12.5-400
      mg/m(2) had been administered via intravenous infusion to 79 patients with
      advanced ovarian cancer enrolled in one of the two clinical studies. Data were
      analyzed by a nonlinear mixed-effects modeling approach. RESULTS: Farletuzumab
      pharmacokinetics was best described by a two-compartment model with first-order
      (linear) elimination. In the final model, estimated values of clearance and
      volume of distribution of the central compartment were 0.00784 l/h and 3.00 l,
      respectively. Body weight was the only covariate investigated that explained
      inter-patient variability in clearance and the central volume of distribution.
      There was no effect of age, human anti-human antibodies, or concomitant
      chemotherapy on the pharmacokinetics of farletuzumab. Simulations showed that,
      when the mg/kg/week dose was maintained, steady-state exposure to farletuzumab
      was similar with dosing every week or every 3 weeks. CONCLUSIONS: The
      pharmacokinetic parameters of farletuzumab are similar to those of other IgG
      mAbs. The results support weight-based dosing of farletuzumab on a weekly or 3
      weekly schedule.

PMID- 22955258
TI  - Phosphorylated AMP-activated protein kinase expression associated with prognosis
      for patients with gastric cancer treated with cisplatin-based adjuvant
      chemotherapy.
AB  - PURPOSE: The present study analyzed the expression of phosphorylated AMP
      activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1
      (PDK-1) and their impact on the survival of patients with resected gastric cancer
      who received cisplatin-based adjuvant chemotherapy. PATIENTS AND METHODS: Korean
      patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy
      with D2 lymph node resection and received a combination regimen of cisplatin and
      S-1 were enrolled. Immunohistochemistry was carried out to determine the
      expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric
      cancer. The expression was divided into two groups according to the intensity
      score (negative: 0 or 1+ and positive: 2+ or 3+). RESULTS: From January 2006 to
      July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty
      patients were included in the pAMPK-positive group, while 33 patients were
      included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression
      was observed in only 10 patients (13.7 %), and there was no or very weak PDK-1
      staining. The clinicopathologic characteristics were similar between the two
      groups according to the expression of pAMPK. With a median follow-up duration of
      26.5 months (2.6-73.2), the estimated 3-year relapse-free survival (RFS) and
      overall survival rates were 55.0 and 78.4 %, respectively. In a multivariate
      analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK
      negative group was significantly associated with improved RFS (Hazard ratio =
      0.459, 95 % CI 0.109-0.711, P = 0.043). CONCLUSION: A low expression of pAMPK was
      found to be correlated with better RFS in patients with resected gastric cancer
      treated with adjuvant cisplatin-based chemotherapy.

PMID- 22955259
TI  - Cyclosporine: does it matter if it is given for Crohn's colitis or ulcerative
      colitis?

PMID- 22955260
TI  - Endoscopic biliary access: endoscopic ultrasound joins the party.

PMID- 22955262
TI  - Magnetic resonance-guided laser-induced thermotherapy in patients with
      oligonodular hepatocellular carcinoma: long-term results over a 15-year period.
AB  - GOALS: To prospectively evaluate the therapeutic potential of magnetic resonance
      (MR)-guided laser-induced thermotherapy (LITT) in patients with oligonodular
      hepatocellular carcinoma. STUDY: A total of 113 patients with 175 intrahepatic
      lesions were treated with MR-guided LITT. The Nd-YAG laser fiber was introduced
      with a percutaneously positioned irrigated laser application system. Qualitative
      and quantitative MR parameters and clinical data were evaluated. Survival data
      were calculated using the Kaplan-Meier method. RESULTS: All patients tolerated
      the procedure well under local anesthesia. The total procedure time was 90
      minutes. All observed complications were minor and no further treatment was
      necessary. Online MR thermometry allowed exact visualization of the extension of
      laser-induced changes and their relationship to the neighboring anatomy. Lesions
      up to 2 cm in diameter could be efficiently treated with a single laser
      application; larger lesions were treated with a dual, triple, and quadruple
      simultaneous application. In 98% of the patients we achieved a complete necrosis
      of the tumor and up to 5 mm of safety margin. The mean survival rate for all
      patients, with calculation started on the date of diagnosis of the HCC nodules
      treated with LITT, was 4.9 years (95% confidence interval, 3.6, 5.1). The median
      survival rate for all patients, with calculation started on the date of diagnosis
      of the HCC nodules treated with LITT, was 3.5 years (95% confidence interval,
      2.7, 4.2). One-year survival was 95%; 2-year survival 72%, 3-year survival 54%;
      and 5-year survival 30%. CONCLUSIONS: In intrahepatic oligonodular involvement of
      hepatocellular carcinoma LITT appears to be an effective therapeutic procedure.

PMID- 22955261
TI  - Racial differences in the association between adiposity measures and the risk of
      hepatitis C-related liver disease.
AB  - BACKGROUND: African Americans have lower reported likelihood of hepatitis C virus
      related cirrhosis than whites. It is unknown whether relative differences in the
      distribution of adipose tissue, lean mass, and other anthropometric measurements
      may explain these observed interethnic differences in disease risk. AIM: : To
      evaluate the association between anthropometric measurements and advanced liver
      disease in a cross-sectional study of African American and white male veterans.
      METHODS: We used the validated FibroSURE-ActiTest to assess hepatic pathology,
      and direct segmental multichannel bioelectric impedance analysis for
      anthropometric measurements. Race-stratified logistic regression was employed to
      evaluate risk of high fibrosis progression rate (FPR) and advanced inflammation
      (A2 to A3). RESULTS: Among 330 eligible males (59% African American), there were
      43 white and 57 African American males with high FPR, and 70 African American and
      59 white with advanced inflammation. Percentage body fat (%BF) was a stronger
      predictor of high FPR risk than was a high body mass index in African Americans
      [odds ratio (OR)(adj)=2.08; 95% confidence interval (CI),0.83-5.23 for highest
      %BF vs. lowest tertile and OR(adj)=1.50; 95% CI,0.60-3.75 for obese vs. normal
      body mass index, respectively], but not in whites. Highest lean leg mass was
      associated with a nonsignificant increased risk of both high FPR and advanced
      inflammation in African Americans (OR(highFPRadj)=1.73; 95% CI, 0.73-4.10;
      OR(AdvancedinflammationAdj)=1.65; 95% CI, 0.76-3.56) versus a decreased risk of
      both in whites (OR(highFPRadj)=0.62; 95% CI, 0.21-1.79;
      OR(AdvancedinflammationAdj)=0.58; 95% CI, 0.22-1.48). CONCLUSIONS: Interethnic
      differences in nontraditional anthropometric measurements like %BF suggests their
      potential role in understanding interethnic differences in hepatitis C virus
      related liver disease risk in males.

PMID- 22955263
TI  - Warfarin and clopidogrel interruption before and after colonoscopic polypectomy:
      results of a survey from a US national audience.

PMID- 22955264
TI  - A pilot study of scheduled endoscopic balloon dilation with oral agent tranilast
      to improve the efficacy of stricture dilation after endoscopic submucosal
      dissection of the esophagus.
AB  - BACKGROUNDS AND AIM: As circumferential or near-circumferential endoscopic
      submucosal dissection (ESD) for superficial esophageal neoplasms might evoke
      refractory strictures, multiple sessions of endoscopic balloon dilation (EBD) are
      required. We aimed to assess the effectiveness and safety of oral agent tranilast
      with EBD for improving the efficacy of stricture dilation after esophageal ESD.
      METHODS: In an open-label prospective study at a single institution, 31
      asymptomatic consecutive patients with superficial esophageal squamous cell
      carcinomas were enrolled from April 2007 to October 2010. After ESD, we performed
      scheduled EBD (twice weekly for 4 wk) with or without administration of oral
      agent tranilast for 8 weeks. Thereafter, we added additional EBD on the basis of
      solid criteria-for example, patient's awareness of vomiting >1/wk and inability
      of passage of routine endoscope through the ESD site. We compared the rates of
      post-ESD strictures and the numbers of additional EBD sessions for 48 weeks after
      ESD and the Dysphagia score between tranilast (T)-group and none (N)-group, based
      on patients' subjective symptoms, at 16, 24, and 48 weeks after ESD. RESULTS: The
      percentage of post-ESD strictures in T-group was significantly lower than that in
      N-group (P=0.04). The median numbers of additional EBD sessions and Dysphagia
      score at 16 and 24 weeks after ESD in T-group were significantly smaller than
      those in N-group (P=0.0138, 0.002, 0.005, respectively). No adverse events and no
      recurrence were observed. CONCLUSIONS: We demonstrated for the first time that
      scheduled EBD combined with oral agent tranilast might be effective and safe for
      improving the efficacy of stricture dilation after esophageal ESD.

PMID- 22955266
TI  - Femtosecond transient absorption spectroscopy of copper(II)-curcumin complexes.
AB  - Ligand-metal interaction between curcumin and Cu(II) in methanol and sodium
      dodecyl sulfate (SDS) micelles was investigated using fluorescence spectroscopy
      and transient absorption spectroscopy. The Cu(II) ion exhibits a high efficiency
      in quenching the fluorescence of curcumin. By quantifying fluorescence quenching
      as a function of Cu(II) concentration, the complexation constants, K(1) and K(2),
      for the formation of the 1 : 1 and 1 : 2 Cu(II)-curcumin complexes, [Cu(II)
      Cur](+) and [Cu(II)-Cur(2)], have been determined. In methanol, K(1) and K(2) are
      (1.33 +/- 0.47) * 10(8) M(-1) and (6.79 +/- 1.77) * 10(5) M(-1), respectively,
      whereas those in SDS micelles are (9.90 +/- 1.68) * 10(5) M(-1) and (1.70 +/-
      0.48) * 10(6) M(-1), respectively. The transient absorption spectra of curcumin
      and the Cu(II)-curcumin complexes from 520 nm to 700 nm show a combination of
      stimulated emission and excited state absorption (ESA). However, the transient
      absorption signal at 500 nm corresponds to ESA exclusively. For curcumin, the ESA
      kinetics exhibit two rising components with time constants of 0.9 ps and 8.2 ps
      in methanol, and 0.5 ps and 2.5 ps in SDS micelles, which are consistent with
      solvation dynamics of excited state curcumin in these media. In addition, the ESA
      kinetics show a decay component with a time constant of 125 ps in methanol and 64
      ps in SDS micelles, reflecting the excited state intramolecular hydrogen atom
      transfer of curcumin in these media. The ESA kinetics of the Cu(II)-curcumin
      complexes exhibit a sharp rise and a fast decay with a time constant of
      approximately 1 ps in both media due to the strong interaction between Cu(II) and
      curcumin.

PMID- 22955269
TI  - Increased phosphoenolpyruvate carboxykinase gene expression and steatosis during
      hepatitis C virus subgenome replication: role of nonstructural component 5A and
      CCAAT/enhancer-binding protein beta.
AB  - Chronic hepatitis C virus (HCV) infection greatly increases the risk for type 2
      diabetes and nonalcoholic steatohepatitis; however, the pathogenic mechanisms
      remain incompletely understood. Here we report gluconeogenic enzyme
      phosphoenolpyruvate carboxykinase (PEPCK) transcription and associated
      transcription factors are dramatically up-regulated in Huh.8 cells, which stably
      express an HCV subgenome replicon. HCV increased activation of cAMP response
      element-binding protein (CREB), CCAAT/enhancer-binding protein (C/EBPbeta),
      forkhead box protein O1 (FOXO1), and peroxisome proliferator-activated receptor
      gamma coactivator 1alpha (PGC-1alpha) and involved activation of the cAMP
      response element in the PEPCK promoter. Infection with dominant-negative CREB or
      C/EBPbeta-shRNA significantly reduced or normalized PEPCK expression, with no
      change in PGC-1alpha or FOXO1 levels. Notably, expression of HCV nonstructural
      component NS5A in Huh7 or primary hepatocytes stimulated PEPCK gene expression
      and glucose output in HepG2 cells, whereas a deletion in NS5A reduced PEPCK
      expression and lowered cellular lipids but was without effect on insulin
      resistance, as demonstrated by the inability of insulin to stimulate mobilization
      of a pool of insulin-responsive vesicles to the plasma membrane. HCV-replicating
      cells demonstrated increases in cellular lipids with insulin resistance at the
      level of the insulin receptor, increased insulin receptor substrate 1 (Ser-312),
      and decreased Akt (Ser-473) activation in response to insulin. C/EBPbeta-RNAi
      normalized lipogenic genes sterol regulatory element-binding protein-1c,
      peroxisome proliferator-activated receptor gamma, and liver X receptor alpha but
      was unable to reduce accumulation of triglycerides in Huh.8 cells or reverse the
      increase in ApoB expression, suggesting a role for increased lipid retention in
      steatotic hepatocytes. Collectively, these data reveal an important role of NS5A,
      C/EBPbeta, and pCREB in promoting HCV-induced gluconeogenic gene expression and
      suggest that increased C/EBPbeta and NS5A may be essential components leading to
      increased gluconeogenesis associated with HCV infection.

PMID- 22955270
TI  - Optimal ratio of transcription factors for somatic cell reprogramming.
AB  - Somatic cell reprogramming is achieved by four reprogramming transcription
      factors (RTFs), Oct3/4, Sox2, Klf4, and c-Myc. However, in addition to the
      induction of pluripotent cells, these RTFs also generate pseudo-pluripotent
      cells, which do not show Nanog promoter activity. Therefore, it should be
      possible to fine-tune the RTFs to produce only fully pluripotent cells. For this
      study, a tagging system was developed to sort induced pluripotent stem (iPS)
      cells according to the expression levels of each of the four RTFs. Using this
      system, the most effective ratio (Oct3/4-high, Sox2-low, Klf4-high, c-Myc-high)
      of the RTFs was 88 times more efficient at producing iPS cells than the worst
      effective ratio (Oct3/4-low, Sox2-high, Klf4-low, c-Myc-low). Among the various
      RTF combinations, Oct3/4-high and Sox2-low produced the most efficient results.
      To investigate the molecular basis, microarray analysis was performed on iPS
      cells generated under high (Oct3/4-high and Sox2-low) and low (Oct3/4-low and
      Sox2-high) efficiency reprogramming conditions. Pathway analysis revealed that
      the G protein-coupled receptor (GPCR) pathway was up-regulated significantly
      under the high efficiency condition and treatment with the chemokine, C-C motif
      ligand 2, a member of the GPCR family, enhanced somatic cell reprogramming 12.3
      times. Furthermore, data from the analysis of the signature gene expression
      profiles of mouse embryonic fibroblasts at 2 days after RTF infection revealed
      that the genetic modifier, Whsc1l1 (variant 1), also improved the efficiency of
      somatic cell reprogramming. Finally, comparison of the overall gene expression
      profiles between the high and low efficiency conditions will provide novel
      insights into mechanisms underlying somatic cell reprogramming.

PMID- 22955271
TI  - The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory
      loop that coordinates lung epithelial cell morphogenesis and differentiation.
AB  - The Grainyhead family of transcription factors controls morphogenesis and
      differentiation of epithelial cell layers in multicellular organisms by
      regulating cell junction- and proliferation-related genes. Grainyhead-like 2
      (Grhl2) is expressed in developing mouse lung epithelium and is required for
      normal lung organogenesis. The specific epithelial cells expressing Grhl2 and the
      genes regulated by Grhl2 in normal lungs are mostly unknown. In these studies we
      identified the NK2-homeobox 1 transcription factor (Nkx2-1) as a direct
      transcriptional target of Grhl2. By binding and transcriptional assays and by
      confocal microscopy we showed that these two transcription factors form a
      positive feedback loop in vivo and in cell lines and are co-expressed in lung
      bronchiolar and alveolar type II cells. The morphological changes observed in
      flattening lung alveolar type II cells in culture are associated with down
      regulation of Grhl2 and Nkx2-1. Reduction of Grhl2 in lung epithelial cell lines
      results in lower expression levels of Nkx2-1 and of known Grhl2 target genes. By
      microarray analysis we identified that in addition to Cadherin1 and Claudin4,
      Grhl2 regulates other cell interaction genes such as semaphorins and their
      receptors, which also play a functional role in developing lung epithelium.
      Impaired collective cell migration observed in Grhl2 knockdown cell monolayers is
      associated with reduced expression of these genes and may contribute to the
      altered epithelial phenotype reported in Grhl2 mutant mice. Thus, Grhl2 functions
      at the nexus of a novel regulatory network, connecting lung epithelial cell
      identity, migration, and cell-cell interactions.

PMID- 22955272
TI  - The retinoblastoma protein selectively represses E2F1 targets via a TAAC DNA
      element during cellular senescence.
AB  - The retinoblastoma (Rb) protein mediates heterochromatin formation at the
      promoters of E2 transcription factor 1 (E2F1) target genes, such as proliferating
      cell nuclear antigen and cyclin A2 (CCNA2), and represses these genes during
      cellular senescence. However, the selectivity of Rb recruitment is still not well
      understood. Here, we demonstrate that a senescence-associated gene is a direct
      target of E2F1 and is also repressed by heterochromatin in senescent cells. In
      contrast, ARF and p27(KIP1), which are also E2F1 targets, are not repressed by Rb
      and heterochromatin formation. By comparing the promoter sequences of these
      genes, we found a novel TAAC element that is present in the cellular senescence
      inhibited gene, proliferating cell nuclear antigen, and CCNA2 promoters but
      absent from the ARF and p27(KIP1) promoters. This TAAC element associates with Rb
      and is required for Rb recruitment. We further determined that TAAC element
      mediated Rb association requires the E2F1 binding site, but not E2F1 protein.
      These results provide a novel molecular mechanism for the different expression
      patterns of E2F1 targets and afford new mechanistic insight regarding the
      selectivity of Rb-mediated heterochromatin formation and gene repression during
      cellular senescence.

PMID- 22955273
TI  - Rapid equilibrium kinetic analysis of arsenite methylation catalyzed by
      recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT).
AB  - In the human body, arsenic is metabolized by methylation. Understanding this
      process is important and provides insight into the relationship between arsenic
      and its related diseases. We used the rapid equilibrium kinetic model to study
      the reaction sequence of arsenite methylation. The results suggest that the
      mechanism for arsenite methylation is a completely ordered mechanism that is also
      of general interest in reaction systems with different reductants, such as tris(2
      carboxyethyl)phosphine, cysteine, and glutathione. In the reaction, cysteine
      residues of recombinant human arsenic (+3 oxidation state) methyltransferase
      (hAS3MT) coordinate with arsenicals and involve the methyl transfer step. S
      Adenosyl-l-methionine (AdoMet) is the first-order reactant, which modulates the
      conformation of hAS3MT to a best matched state by hydrophobic interaction. As the
      second-order reactant, reductant reduces the disulfide bond, most likely between
      Cys-250 and another cysteine residue of hAS3MT, and exposes the active site
      cysteine residues for binding trivalent inorganic arsenic (iAs(3+)) to give
      monomethylarsonic dicysteine (MADC(3+)). In addition, the reaction can be
      extended to further methylate MADC(3+) to dimethylarsinic cysteine (DAMC(3+)). In
      the methylation reaction, the beta-pleated sheet content of hAS3MT is increased,
      and the hydrophobicity of the microenvironment around the active sites is
      decreased. Similarly, we confirm that both the high beta-pleated sheet content of
      hAS3MT and the high dissociation ability of the enzyme-AdoMet-reductant improve
      the yield of dimethylated arsenicals.

PMID- 22955274
TI  - Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor-alpha
      translation through a SHIP1-dependent pathway.
AB  - Production of the proinflammatory cytokine TNFalpha by activated macrophages is
      an important component of host defense. However, TNFalpha production must be
      tightly controlled to avoid pathological consequences. The anti-inflammatory
      cytokine IL-10 inhibits TNFalpha mRNA expression through activation of the STAT3
      transcription factor pathway and subsequent expression of STAT3-dependent gene
      products. We hypothesized that IL-10 must also have more rapid mechanisms of
      action and show that IL-10 rapidly shifts existing TNFalpha mRNA from
      polyribosome-associated polysomes to monosomes. This translation suppression
      requires the presence of SHIP1 (SH2 domain-containing inositol 5'-phosphatase 1)
      and involves inhibition of Mnk1 (MAPK signal-integrating kinase 1). Furthermore,
      activating SHIP1 using a small-molecule agonist mimics the inhibitory effect of
      IL-10 on Mnk1 phosphorylation and TNFalpha translation. Our data support the
      existence of an alternative STAT3-independent pathway through SHIP1 for IL-10 to
      regulate TNFalpha translation during the anti-inflammatory response.

PMID- 22955275
TI  - ATF4-dependent regulation of the JMJD3 gene during amino acid deprivation can be
      rescued in Atf4-deficient cells by inhibition of deacetylation.
AB  - Following amino acid deprivation, the amino acid response (AAR) induces
      transcription from specific genes through a collection of signaling mechanisms,
      including the GCN2-eIF2-ATF4 pathway. The present report documents that the
      histone demethylase JMJD3 is an activating transcription factor 4 (ATF4)
      dependent target gene. The JMJD3 gene contains two AAR-induced promoter
      activities and chromatin immunoprecipitation (ChIP) analysis showed that the AAR
      leads to enhanced ATF4 recruitment to the C/EBP-ATF response element (CARE)
      upstream of Promoter-1. AAR-induced histone modifications across the JMJD3 gene
      locus occur upon ATF4 binding. Jmjd3 transcription is not induced in Atf4-knock
      out cells, but the AAR-dependent activation was rescued by inhibition of histone
      deacetylation with trichostatin A (TSA). The TSA rescue of AAR activation in the
      absence of Atf4 also occurred for the Atf3 and C/EBP homology protein (Chop)
      genes, but not for the asparagine synthetase gene. ChIP analysis of the Jmjd3,
      Atf3, and Chop genes in Atf4 knock-out cells documented that activation of the
      AAR in the presence of TSA led to specific changes in acetylation of histone H4.
      The results suggest that a primary function of ATF4 is to recruit histone
      acetyltransferase activity to a sub-set of AAR target genes. Thus, absolute
      binding of ATF4 to these particular genes is not required and no ATF4 interaction
      with the general transcription machinery is necessary. The data are consistent
      with the hypothesis that ATF4 functions as a pioneer factor to alter chromatin
      structure and thus, enhance transcription in a gene-specific manner.

PMID- 22955277
TI  - Structural understanding of the glutathione-dependent reduction mechanism of
      glutathionyl-hydroquinone reductases.
AB  - Glutathionyl-hydroquinone reductases (GS- HQRs) are a newly identified group of
      glutathione transferases, and they are widely distributed in bacteria,
      halobacteria, fungi, and plants. GS-HQRs catalyze glutathione (GSH)-dependent
      reduction of glutathionyl-hydroquinones (GS-hydroquinones) to hydroquinones. GS
      hydroquinones can be spontaneously formed from benzoquinones reacting with
      reduced GSH via Michael addition, and GS-HQRs convert the conjugates to
      hydroquinones. In this report we have determined the structures of two bacterial
      GS-HQRs, PcpF of Sphingobium chlorophenolicum and YqjG of Escherichia coli. The
      two structures and the previously reported structure of a fungal GS-HQR shared
      many features and displayed complete conservation for all the critical residues.
      Furthermore, we obtained the binary complex structures with GS-menadione, which
      in its reduced form, GS-menadiol, is a substrate. The structure revealed a large
      H-site that could accommodate various substituted hydroquinones and a hydrogen
      network of three Tyr residues that could provide the proton for reductive
      deglutathionylation. Mutation of the Tyr residues and the position of two GSH
      molecules confirmed the proposed mechanism of GS-HQRs. The conservation of GS
      HQRs across bacteria, halobacteria, fungi, and plants potentiates the
      physiological role of these enzymes in quinone metabolism.

PMID- 22955276
TI  - Human Pumilio proteins recruit multiple deadenylases to efficiently repress
      messenger RNAs.
AB  - PUF proteins are a conserved family of eukaryotic RNA-binding proteins that
      regulate specific mRNAs: they control many processes including stem cell
      proliferation, fertility, and memory formation. PUFs repress protein expression
      from their target mRNAs but the mechanism by which they do so remains unclear,
      especially for humans. Humans possess two PUF proteins, PUM1 and PUM2, which
      exhibit similar RNA binding specificities. Here we report new insights into their
      regulatory activities and mechanisms of action. We developed functional assays to
      measure sequence-specific repression by PUM1 and PUM2. Both robustly inhibit
      translation and promote mRNA degradation. Purified PUM complexes were found to
      contain subunits of the CCR4-NOT (CNOT) complex, which contains multiple enzymes
      that catalyze mRNA deadenylation. PUMs interact with the CNOT deadenylase
      subunits in vitro. We used three approaches to determine the importance of
      deadenylases for PUM repression. First, dominant-negative mutants of CNOT7 and
      CNOT8 reduced PUM repression. Second, RNA interference depletion of the
      deadenylases alleviated PUM repression. Third, the poly(A) tail was necessary for
      maximal PUM repression. These findings demonstrate a conserved mechanism of PUF
      mediated repression via direct recruitment of the CCR4-POP2-NOT deadenylase
      leading to translational inhibition and mRNA degradation. A second, deadenylation
      independent mechanism was revealed by the finding that PUMs repress an mRNA that
      lacks a poly(A) tail. Thus, human PUMs are repressors capable of deadenylation
      dependent and -independent modes of repression.

PMID- 22955278
TI  - Glycogen synthase kinase is a regulator of the circadian clock of Neurospora
      crassa.
AB  - Timekeeping by circadian clocks relies upon precise adjustment of expression
      levels of clock proteins. Here we identify glycogen synthase kinase (GSK) as a
      novel and critical component of the circadian clock of Neurospora crassa that
      regulates the abundance of its core transcription factor white collar complex
      (WCC) on a post-transcriptional level. We show that GSK specifically binds and
      phosphorylates both subunits of the WCC. Reduced expression of GSK promotes an
      increased accumulation of WC-1, the limiting factor of the WCC, causing an
      acceleration of the circadian clock and a shorter free-running period.

PMID- 22955279
TI  - Biochemical mechanism of HIV-1 resistance to rilpivirine.
AB  - Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT)
      inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first generation
      NNRTIs. Virological failure during therapy with RPV and emtricitabine is
      associated with the appearance of E138K and M184I mutations in RT. Here we
      investigate the biochemical mechanism of RT inhibition and resistance to RPV. We
      used two transient kinetics approaches (quench-flow and stopped-flow) to
      determine how subunit-specific mutations in RT p66 or p51 affect association and
      dissociation of RPV to RT as well as their impact on binding of dNTP and DNA and
      the catalytic incorporation of nucleotide. We compared WT with four subunit
      specific RT mutants, p66(M184I)/p51(WT), p66(E138K)/p51(E138K),
      p66(E138K/M184I)/p51(E138K), and p66(M184I)/p51(E138K). Ile-184 in p66
      (p66(184I)) decreased the catalytic efficiency of RT (k(pol)/K(d)(.dNTP)),
      primarily through a decrease in dNTP binding (K(d)(.dNTP)). Lys-138 either in
      both subunits or in p51 alone abrogated the negative effect of p66(184I) by
      restoring dNTP binding. Furthermore, p51(138K) reduced RPV susceptibility by
      altering the ratio of RPV dissociation to RPV association, resulting in a net
      reduction in RPV equilibrium binding affinity (K(d)(.RPV) =
      k(off.RPV)/k(on.RPV)). Quantum mechanics/molecular mechanics hybrid molecular
      modeling revealed that p51(E138K) affects access to the RPV binding site by
      disrupting the salt bridge between p51(E138) and p66(K101). p66(184I) caused
      repositioning of the Tyr-183 active site residue and decreased the efficiency of
      RT, whereas the addition of p51(138K) restored Tyr-183 to a WT-like conformation,
      thus abrogating the Ile-184-induced functional defects.

PMID- 22955280
TI  - Activation of nuclear factor kappaB (NF-kappaB) in prostate cancer is mediated by
      protein kinase C epsilon (PKCepsilon).
AB  - Protein kinase C epsilon (PKCepsilon) has emerged as an oncogenic kinase and
      plays important roles in cell survival, mitogenesis and invasion. PKCepsilon is
      up-regulated in most epithelial cancers, including prostate, breast, and lung
      cancer. Here we report that PKCepsilon is an essential mediator of NF-kappaB
      activation in prostate cancer cells. A strong correlation exists between
      PKCepsilon overexpression and NF-kappaB activation status in prostate cancer
      cells. Moreover, transgenic overexpression of PKCepsilon in the mouse prostate
      causes preneoplastic lesions that display significant NF-kappaB hyperactivation.
      PKCepsilon RNAi depletion or inhibition in prostate cancer cells diminishes NF
      kappaB translocation to the nucleus with subsequent impairment of both activation
      of NF-kappaB transcription and induction of NF-kappaB responsive genes in
      response to the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha).
      On the other hand, PKCepsilon overexpression in normal prostate cells enhances
      activation of the NF-kappaB pathway. A mechanistic analysis revealed that
      TNFalpha activates PKCepsilon via a C1 domain/diacylglycerol-dependent mechanism
      that involves phosphatidylcholine-phospholipase C. Moreover, PKCepsilon
      facilitates the assembly of the TNF receptor-I signaling complex to trigger NF
      kappaB activation. Our studies identified a molecular link between PKCepsilon and
      NF-kappaB that controls key responses implicated in prostate cancer progression.

PMID- 22955281
TI  - Mapping protein-protein proximity in the purinosome.
AB  - The enzymes in the human de novo purine synthesis pathway were found to form a
      cellular complex, the purinosome, upon culturing cells in purine-depleted medium
      (An, S., Kumar R., Sheets, E. D., and Benkovic, S. J. (2008) Science 320, 103
      106). Purinosome formation and dissociation were found to be modulated by several
      factors, including the microtubule network and cell signaling involving protein
      phosphorylation. To determine whether the pathway enzymes are in physical
      contact, we probed for the protein-protein interactions (PPIs) within the
      purinosome with a novel application of the Tango PPI reporter system (Barnea, G.,
      Strapps, W., Herrada, G., Berman, Y., Ong, J., Kloss, B., Axel, R., and Lee, K.
      J. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 64-69). We found PPIs among all six
      enzymes within the pathway and evidence for a core involving the first three
      enzymes. We also captured purinosomes under both purine-rich and purine-depleted
      conditions. The results provide additional insights into the transient nature and
      topography of the purinosome.

PMID- 22955282
TI  - Toll-like receptor 4 is expressed on intestinal stem cells and regulates their
      proliferation and apoptosis via the p53 up-regulated modulator of apoptosis.
AB  - Factors regulating the proliferation and apoptosis of intestinal stem cells
      (ISCs) remain incompletely understood. Because ISCs exist among microbial
      ligands, immune receptors such as toll-like receptor 4 (TLR4) could play a role.
      We now hypothesize that ISCs express TLR4 and that the activation of TLR4
      directly on the intestinal stem cells regulates their ability to proliferate or
      to undergo apoptosis. Using flow cytometry and fluorescent in situ hybridization
      for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed
      on the Lgr5-positive intestinal stem cells. TLR4 activation reduced proliferation
      and increased apoptosis in ISCs both in vivo and in ISC organoids, a finding not
      observed in mice lacking TLR4 in the Lgr5-positive ISCs, confirming the in vivo
      significance of this effect. To define molecular mechanisms involved, TLR4
      inhibited ISC proliferation and increased apoptosis via the p53-up-regulated
      modulator of apoptosis (PUMA), as TLR4 did not affect crypt proliferation or
      apoptosis in organoids or mice lacking PUMA. In vivo effects of TLR4 on ISCs
      required TIR-domain-containing adapter-inducing interferon-beta (TRIF) but were
      independent of myeloid-differentiation primary response-gene 88 (MYD88) and
      TNFalpha. Physiological relevance was suggested, as TLR4 activation in
      necrotizing enterocolitis led to reduced proliferation and increased apoptosis of
      the intestinal crypts in a manner that could be reversed by inhibition of PUMA,
      both globally or restricted to the intestinal epithelium. These findings
      illustrate that TLR4 is expressed on ISCs where it regulates their proliferation
      and apoptosis through activation of PUMA and that TLR4 regulation of ISCs
      contributes to the pathogenesis of necrotizing enterocolitis.

PMID- 22955283
TI  - Extracellular signal-regulated kinase 2 (ERK2) mediates phosphorylation and
      inactivation of nuclear interaction partner of anaplastic lymphoma kinase (NIPA)
      at G2/M.
AB  - NIPA is an F-box-like protein that contributes to the timing of mitotic entry. It
      targets nuclear cyclin B1 for ubiquitination in interphase, whereas in G(2)/M
      phase, NIPA is inactivated by phosphorylation to allow for cyclin B1
      accumulation, a critical event for proper G(2)/M transition. We recently
      specified three serine residues of NIPA and demonstrated a sequential
      phosphorylation at G(2)/M, where initial Ser-354 and Ser-359 phosphorylation is
      most crucial for SCF(NIPA) inactivation. In this study, we identified ERK2 as the
      kinase responsible for this critical initial phosphorylation step. Using in vitro
      kinase assays, we found that both ERK1 and ERK2 phosphorylated NIPA with high
      efficiency. Mutation of either Ser-354 or Ser-359 abolished ERK-dependent NIPA
      phosphorylation. Pharmacologic inhibition of ERK1/2 in cell lines resulted in
      decreased NIPA phosphorylation at G(2)/M. By combining cell cycle synchronization
      with stable expression of shRNA targeting either ERK1 or ERK2, we showed that
      ERK2 but not ERK1 mediated NIPA inactivation at G(2)/M. ERK2 knockdown led to a
      delay at the G(2)/M transition, a phenotype also observed in cells expressing a
      phospho-deficient mutant of NIPA. Thus, our data add to the recently described
      divergent functions of ERK1 and ERK2 in cell cycle regulation, which may be due
      in part to the differential ability of these kinases to phosphorylate and
      inactivate NIPA at G(2)/M.

PMID- 22955284
TI  - Nectin-1 binds and signals through the fibroblast growth factor receptor.
AB  - Nectins belong to a family of immunoglobulin (Ig)-like cell-adhesion molecules
      comprising four members, nectin-1 through nectin-4. Nectins are involved in
      formation of the mechanical adhesive puncta adherentia junctions of synapses.
      Nectins share the same overall structural topology with an extracellular region
      containing three Ig modules, a transmembrane region, and a cytoplasmic region. In
      nectin-1, the first and second Ig module in the extracellular region are
      necessary for the trans-interaction with nectin-3 and formation of cis-dimers,
      respectively. The function of the third Ig module of nectin-1 remains unknown. We
      here report the structure in solution of the third, membrane-proximal Ig module
      of mouse nectin-1 (nectin-1 Ig3) solved by means of nuclear magnetic resonance
      (NMR) spectroscopy. It belongs to the C1 set of the Ig superfamily. Nectin-1 Ig3
      was produced as a recombinant protein and induced neurite outgrowth in primary
      cultures of hippocampal and cerebellar granule neurons, an effect abolished by
      treatment with the fibroblast growth factor receptor (FGFR) inhibitor SU5402, or
      by transfection with a dominant-negative FGFR1 construct. We showed by surface
      plasmon resonance (SPR) analysis that nectin-1 Ig3 directly interacted with
      various isoforms of FGFR. Nectin-1 Ig3 induced phosphorylation of FGFR1c in the
      same manner as the whole nectin-1 ectodomain, and promoted survival of cerebellar
      granule neurons induced to undergo apoptosis. Finally, we constructed a peptide,
      nectide, by employing in silico modeling of various FGFR ligand-binding sites.
      Nectide mimicked all the effects of nectin-1 Ig3. We suggest that FGFR is a
      downstream signaling partner of nectin-1.

PMID- 22955285
TI  - Actopaxin (alpha-parvin) phosphorylation is required for matrix degradation and
      cancer cell invasion.
AB  - Dysregulation of cell adhesion and motility is known to be an important factor in
      the development of tumor malignancy. Actopaxin (alpha-parvin) is a paxillin,
      integrin-linked kinase, and F-actin binding focal adhesion protein with several
      serine phosphorylation sites in the amino terminus that contribute to the
      regulation of cell spreading and migration. Here, phosphorylation of actopaxin is
      shown to contribute to the regulation of matrix degradation and cell invasion.
      Osteosarcoma cells stably expressing wild type (WT), nonphosphorylatable (Quint),
      and phosphomimetic (S4D/S8D) actopaxin demonstrate that actopaxin phosphorylation
      is necessary for efficient Src and matrix metalloproteinase-driven degradation of
      extracellular matrix. Rac1 was found to be required for actopaxin-induced matrix
      degradation whereas inhibition of myosin contractility promoted degradation in
      the phosphomutant-expressing Quint cells, indicating that a balance of Rho GTPase
      signaling and regulation of cellular tension are important for the process.
      Furthermore, actopaxin forms a complex with the Rac1/Cdc42 GEF beta-PIX and
      Rac1/Cdc42 effector PAK1, to regulate actopaxin-dependent matrix degradation.
      Actopaxin phosphorylation is elevated in the invasive breast cancer cell line MDA
      MB-231 compared with normal breast epithelial MCF10A cells. Expression of the
      nonphosphorylatable Quint actopaxin in MDA-MB-231 cells inhibits cell invasion
      whereas overexpression of WT actopaxin promotes invasion in MCF10A cells. Taken
      together, this study demonstrates a new role for actopaxin phosphorylation in
      matrix degradation and cell invasion via regulation of Rho GTPase signaling.

PMID- 22955286
TI  - Failure of prion protein oxidative folding guides the formation of toxic
      transmembrane forms.
AB  - The mechanism by which pathogenic mutations in the globular domain of the
      cellular prion protein (PrP(C)) increase the likelihood of misfolding and
      predispose to diseases is not yet known. Differences in the evidences provided by
      structural and metabolic studies of these mutants suggest that in vivo folding
      could be playing an essential role in their pathogenesis. To address this role,
      here we use the single or combined M206S and M213S artificial mutants causing
      labile folds and express them in cells. We find that these mutants are highly
      toxic, fold as transmembrane PrP, and lack the intramolecular disulfide bond.
      When the mutations are placed in a chain with impeded transmembrane PrP
      formation, toxicity is rescued. These results suggest that oxidative folding
      impairment, as on aging, can be fundamental for the genesis of intracellular
      neurotoxic intermediates key in prion neurodegenerations.

PMID- 22955287
TI  - Chaperone activity of small heat shock proteins underlies therapeutic efficacy in
      experimental autoimmune encephalomyelitis.
AB  - To determine whether the therapeutic activity of alphaB crystallin, small heat
      shock protein B5 (HspB5), was shared with other human sHsps, a set of seven human
      family members, a mutant of HspB5 G120 known to exhibit reduced chaperone
      activity, and a mycobacterial sHsp were expressed and purified from bacteria.
      Each of the recombinant proteins was shown to be a functional chaperone, capable
      of inhibiting aggregation of denatured insulin with varying efficiency. When
      injected into mice at the peak of disease, they were all effective in reducing
      the paralysis in experimental autoimmune encephalomyelitis. Additional structure
      activity correlations between chaperone activity and therapeutic function were
      established when linear regions within HspB5 were examined. A single region,
      corresponding to residues 73-92 of HspB5, forms amyloid fibrils, exhibited
      chaperone activity, and was an effective therapeutic for encephalomyelitis. The
      linkage of the three activities was further established by demonstrating
      individual substitutions of critical hydrophobic amino acids in the peptide
      resulted in the loss of all of the functions.

PMID- 22955288
TI  - Peripherally inserted central catheter tip position and risk of associated
      complications in neonates.
AB  - OBJECTIVE: To characterize the relationship between peripherally inserted central
      catheters (PICC) tip positions and associated complications in neonates. STUDY
      DESIGN: Catheter tip position for 319 infants was classified into superior vena
      cava (SVC, n=131), inferior vena cava (IVC, n=72), brachiocephalic (BC, n=59),
      midclavicular (MC, n=49) or iliac. Duration of catheter stay and complication
      profile was compared between central (SVC/IVC) vs non-central PICC, and between
      SVC vs IVC, SVC vs BC and SVC vs MC. Kaplan-Meier survival analysis and
      regression models were used. RESULT: Overall length of catheter stay was similar
      between central and non-central group. Non-central catheters (n=116) had higher
      complication rates (47 vs 29%; P=0.001), non-elective removals (45 vs 27%;
      P=0.002) and shorter time to complication (6.2 vs 11.4 days; P=0.043). This
      difference was primarily due to the complications encountered in MC group, which
      had the highest rate of infiltration (P<0.001) and mechanical complications while
      outcomes were similar among other subgroups. Interestingly, catheter survival
      probability was similar in all groups for first 4 days. Rate and types of blood
      stream infections were not related to catheter tip position. CONCLUSION: Non
      central PICCs are associated with higher rates of infiltration and mechanical
      complications when the tip is in MC region. BC catheters may have comparable
      outcomes to SVC in neonates. A careful risk-benefit analysis is warranted when MC
      catheters are used in neonates.

PMID- 22955289
TI  - Post transfusion lung injury in the neonatal population.
AB  - OBJECTIVE: The objective of this study was to examine the changes in level of
      respiratory support following transfusion in neonates who require intermediate or
      intensive care. STUDY DESIGN: Data on respiratory support were collected
      retrospectively from the medical record before, during and after transfusion.
      Neonatal post transfusion lung injury (NPTLI) was defined as an increase in the
      highest mean airway pressure (MAP) of >=2 cm H(2)O or FiO(2) >0.15 in the 6-h
      after transfusion that persisted from 6 to 18 h post transfusion. RESULT: A total
      of 373 (330 packed red blood cell) transfusions were given to 108 infants. NPTLI
      occurred following 31 (8.3%) transfusions in 23 patients. During the first 6 h
      after transfusion, FiO2 or MAP was increased in 47 transfusions (12.6%) and the
      changes persisted in 31 transfusions (7.8%). Infants who developed NPTLI were
      less mature (27.1+/-0.7 vs 31.0+/-0.5 weeks; P=0.005) and of lower birth weight
      (1001+/-110 vs1692+/-104 g; P=0.001). Infants who developed NPTLI were more
      likely to develop necrotizing enterocolitis (6/24 vs 4/85; P=0.002) and die
      within 24 h of transfusion (5/22 vs 3/85; P=0.003). CONCLUSION: In neonates
      receiving intensive or intermediate care, blood transfusion was associated with
      need for increased respiratory support in a significant number of cases.
      Development of NPTLI was associated with poorer outcomes.

PMID- 22955291
TI  - Preparation and structures of coordination complexes of the very hard Lewis acids
      ZrF4 and HfF4.
AB  - [MF(4)(dmso)(2)] (M = Zr or Hf) and [MF(4)(dmf)(2)], prepared by dissolving
      MF(4).nH(2)O in the appropriate solvent, have been used as synthons for a range
      of complexes of these otherwise intractable tetrafluorides. These reagents react
      with OPR(3) (R = Me or Ph) or OAsPh(3) (L) in anhydrous CH(2)Cl(2) to form six
      coordinate [MF(4)L(2)] which exist as a mixture of cis (predominant form) and
      trans isomers in CH(2)Cl(2) solution but which crystallise as trans (OPPh(3),
      OAsPh(3)) or cis (OPMe(3)) forms. Cis-[ZrF(4)(OAsPh(3))(2)] crystals were
      obtained from MeCN. Cis-[MF(4)(pyNO)(2)] and eight-coordinate (distorted
      dodecahedral) [MF(4)(L-L)(2)] (L-L = 2,2'-bipy, or 1,10-phen), and [MF(4)(Me(4)
      cyclam)] were also obtained. Attempts to prepare complexes with the N
      heterocyclic carbene, 1,3-(2,6-di-isopropylphenyl)imidazol-2-ylidene (IDiPP) or
      alkyl diphosphines were unsuccessful. Crystal structures are reported for trans
      [ZrF(4)(OPPh(3))(2)], cis- and trans-[ZrF(4)(OAsPh(3))(2)], cis
      [HfF(4)(OPMe(3))(2)], [ZrF(4)(2,2'-bipy)(2)], cis-[HfF(4)(dmf)(2)], and geometric
      isomers (both pentagonal bipyramidal) of [(dmso)(2)F(3)M(MU-F)(2)MF(3)(dmso)(2)].
      The failed attempts to make IDiPP adducts led to crystals of
      [IDiPPH](3)[M(3)F(15)] containing discrete anions based upon a triangle of M
      atoms with single F bridges. The results are compared with previous work on
      TiF(4) adducts and with complexes of MCl(4), and demonstrate that the MF(4) are
      very hard Lewis acids, with a marked preference for O- over N-donors.

PMID- 22955290
TI  - Development of prognostic tools in pulmonary arterial hypertension: lessons from
      modern day registries.
AB  - Pulmonary arterial hypertension (PAH) is characterised by increased pressure in
      the pulmonary arteries leading to right-sided ventricular failure, and death.
      Identification of factors that affect patient survival is important to improve
      patient management and outcomes. The first registry to evaluate survival and
      develop a prognostic model was the National Institutes of Health (NIH) registry
      in 1981. Importantly this prognostic model is based on data collected prior to
      availability of PAH-targeted therapies and does not reflect survival rates for
      treated patients. Since the 1980s, however, four modern registries of PAH now
      exist which compensate for the NIH equations shortcomings and include the French
      National registry, Pulmonary Hypertension Connection registry, the Mayo registry,
      and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).
      The similarities and difference in these registries are highlighted in this
      review and although similar in many respects, the four registries vary in patient
      population, including the numbers of newly and previously diagnosed patients, as
      well as the era of observation, period of survival, and timing of assessment of
      potential predictive factors. Despite this, the predictive factors identified in
      each registry and described in detail within the body of this manuscript share
      surprising homology in that disease aetiology, patient gender and factors
      reflective of right heart failure are integral in depicting survival. Future
      modifications of modern prognostic equations should be an ongoing goal of the PAH
      community in order to provide increased accuracy with identification of novel
      risk factors and prediction of disease course.

PMID- 22955292
TI  - The effect of long-term nicotine exposure on bone mineral density and oxidative
      stress in female Swiss Albino rats.
AB  - PURPOSE: To evaluate the effect of long-term low or high-dose nicotine exposure
      on bone mass via measuring bone mineral density (BMD) and oxidant-antioxidant
      status markers. METHODS: Thirty-five female Swiss Albino rats weighing 70 +/- 10
      g were divided as the control group (n = 12), low-dose nicotine group (n = 12)
      and high-dose nicotine group (n = 11). While the control group was given only
      normal drinking water, the low-dose nicotine group had 0.4 mg/kg per day and the
      high-dose nicotine group, 6.0 mg/kg per day of nicotine added to their water for
      the period of 1 year. BMD was determined with X-ray absorptiometry of lumbar
      vertebra, corpus femoris, proximal and distal femur. To evaluate oxidant
      antioxidant status malondialdehyde (MDA) levels, superoxide dismutase (SOD) and
      catalase (CAT) activities were determined. RESULTS: When comparing the nicotine
      groups and controls, neither BMD nor oxidant-antioxidant status markers showed
      any statistically significant difference. In comparison to the controls, 12
      months of high-dose oral nicotine exposure did not have a significant effect on
      BMD and low-dose nicotine exposure led to a statistically insignificant increase
      in BMD. CONCLUSIONS: Contrary to common belief, the results of this study show
      that nicotine is not responsible for the decrease in BMD leading to osteoporosis
      frequently seen in smokers. However, there is a need to explore the other harmful
      materials in tobacco which may be responsible for the alterations seen in BMD of
      smokers.

PMID- 22955293
TI  - Pregnancy with dilated and peripartum cardiomyopathy: maternal and fetal outcome.
AB  - BACKGROUND: A retrospective review of the records of all the patients of dilated
      cardiomyopathy (DCM) with pregnancy at PGIMER, Chandigarh, India, in order to
      find out maternal and fetal outcome. MATERIALS AND METHODS: We did a
      retrospective analysis of records of diagnosed cases of DCM from 1994 to 2010.
      There were records of 38 patients who had DCM with pregnancy. Detailed history
      was followed by systemic examination, routine investigations and
      echocardiography. Multidisciplinary care was given to these women by
      obstetrician, cardiologist, anesthetist and neonatologist. Pharmacotherapy
      consisted to diuretics, alpha and beta blockers and heparin or low-dose aspirin
      for thrombo prophylaxis. Elective induction of labor was advised after 37 weeks
      of gestation subject to favorability of cervix. RESULTS: Out of 1,472 patients of
      heart disease during study period, 38 women had DCM. Out of these, 8 (21 %) had
      idiopathic cardiomyopathy, two had DCM due to thyrotoxicosis and 28 (73.6 %)
      patients had peripartum cardiomyopathy. Mean gestational age at the time of
      presentation was 35 weeks. Majority of the patients (19/38) presented with
      complaints of exertional dyspnoea. Mean LVEF at the time of diagnosis was 32.28
      %. There were six (15.8 %) maternal deaths and all of them had global hypokinesia
      on echocardiography and presented in NYHA class IV. Fetal outcome too depended
      upon maternal cardiac status. There were eight stillbirths and all the patients
      who had IUFD belonged to class IV. Twelve patients (40 %) had preterm delivery.
      Mean birth weight of babies was 2 kg.

PMID- 22955295
TI  - MALDI-imaging segmentation is a powerful tool for spatial functional proteomic
      analysis of human larynx carcinoma.
AB  - PURPOSE: For several decades, conventional histological staining and
      immunohistochemistry (IHC) have been the main tools to visualize and understand
      tissue morphology and structure. IHC visualizes the spatial distribution of
      individual protein species directly in tissue. However, a specific antibody is
      required for each protein, and multiplexing capabilities are extremely limited,
      rarely visualizing more than two proteins simultaneously. With the recent
      emergence of matrix-assisted laser desorption/ionization imaging mass
      spectrometry (MALDI-imaging), it is becoming possible to study more complex
      proteomic patterns directly in tissue. However, the analysis and interpretation
      of large and complex MALDI-imaging data requires advanced computational methods.
      In this paper, we show how the recently introduced method of spatial segmentation
      can be applied to analysis and interpretation of a larynx carcinoma section and
      compare the spatial segmentation with the histological annotation of the same
      tissue section. METHODS: Matrix-assisted laser desorption/ionization imaging is a
      label-free spatially resolved analytical technique, which allows detection and
      visualization of hundreds of proteins at once. Spatial segmentation of the MALDI
      imaging data by clustering of spectra by their similarity was performed,
      automatically generating a spatial segmentation map of the tissue section, where
      regions of similar proteomic patterns were highlighted. The tissue was stained
      with the hematoxylin and eosin (H&E), histopathologically analyzed and annotated.
      The segmentation map was interpreted after its overlay with the H&E microscopy
      image. RESULTS: The automatically generated segmentation map exhibits high
      correspondence to the detailed histological annotation of the larynx carcinoma
      tissue section. By superimposing, the segmentation map based on the proteomic
      profiles with H&E-stained microscopic images, we demonstrate precise localization
      of complex and histopathologically relevant tissue features in an automated way.
      CONCLUSIONS: The combination of MALDI-imaging and automatic spatial segmentation
      is a useful approach in analyzing carcinoma tissue and provides a deeper insight
      into the functional proteomic organization of the respective tissue.

PMID- 22955296
TI  - A new method to facilitate oro-tracheal intubation of awake patients:  a pilot
      study.

PMID- 22955297
TI  - [Early diagnosis of hepatitis C transmission after needlestick injury].
AB  - Occupational transmission of hepatitis C (HCV) is rare but has been repeatedly
      described in the published literature. Early diagnosis and therapy of acute
      hepatitis C is associated with an excellent chance of permanent HCV elimination.
      The majority of chronic HCV infections, however, lead to a slowly progressive
      hepatitis with associated morbidity and risk of liver cirrhosis. For this reason
      the need for antiviral therapy has to be evaluated immediately. 

PMID- 22955298
TI  - Context for practice: Scope and standards of practice for WOC nursing.

PMID- 22955300
TI  - Predicting the development of pressure ulcers and the "ostrich syndrome".

PMID- 22955302
TI  - The CAET Academy Knowledge to Practice Program--culturally competent continuing
      education.

PMID- 22955303
TI  - WOC nurse and practice innovation.

PMID- 22955305
TI  - Critical analysis of a wound care certification question.

PMID- 22955306
TI  - Air-fluidized therapy in patients with suspected deep tissue injury: a case
      series.
AB  - PURPOSE: The evolution of suspected deep tissue injuries from an initial purple
      bruise to a significant stage III or IV pressure ulcer may be rapid, even with
      optimal treatment. This case series describes our experience with air-fluidized
      therapy (AFT) placed upon discovery of suspected deep tissue injury (sDTI) in an
      acute care setting. CASES: Five patients with 10 sDTIs were placed on AFT within
      12 hours of sDTI diagnosis and evaluated for an average of 9 days. Patients were
      included in the series if they met the height and weight range of the bed and
      presented with, or developed an sDTI. Standard wound care included the use of an
      ointment containing trypsin, Balsam of Peru, and castor oil (Vasolex; Stratus
      Pharmaceuticals Inc, Miami, Florida) applied directly to both intact skin and
      open areas comprising the sDTI. Patients were repositioned per standard hospital
      care. Although we were unable to prevent skin breakdown in every case, findings
      suggest that interventions resulted in a reduction in the magnitude of tissue
      loss, including prevention of stage III to IV pressure ulceration in all 5
      patients. The cost of a 9-day length of stay on the AFT bed is estimated at less
      than $700 per patient, which is far less than the reported cost to treat a stage
      III/IV wound ($10,845 US per patient in 2009 dollars). CONCLUSION: Our experience
      described in these cases suggests that the use of AFT may be clinical and cost
      effective for prevention of progression of sDTI in critically ill patients.
      Additional research in this area should be encouraged.

PMID- 22955308
TI  - Progestogens for preterm birth prevention: a systematic review and meta-analysis.
AB  - OBJECTIVE: We systematically reviewed the effectiveness of progestogens for
      prevention of preterm birth among women with prior spontaneous preterm birth,
      multiple gestations, preterm labor, short cervix, or other indications. DATA
      SOURCES: We searched MEDLINE and EMBASE databases for English language articles
      published from January 1966 to October 2011. METHODS OF STUDY SELECTION: We
      excluded publications that were not randomized controlled trials or had fewer
      than 20 participants, identifying 34 publications, of which 19 contained data for
      Bayesian meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Two reviewers
      independently extracted data and assigned overall quality ratings based on
      predetermined criteria. Among women with prior preterm birth and a singleton
      pregnancy (five randomized controlled trials), progestogen treatment decreased
      the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian
      credible interval 0.68-0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian
      credible interval 0.27-0.98). The evidence suggests progestogen treatment does
      not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87-1.17) or
      neonatal death (RR 1.44, 95% Bayesian credible interval 0.46-3.18) in multiple
      gestations. Limited evidence suggests progestogen treatment may prevent
      prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval
      0.47-0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36-0.70).
      Across indications, evidence about maternal, fetal, or neonatal health outcomes,
      other than reducing preterm birth and neonatal mortality, is inconsistent,
      insufficient, or absent. CONCLUSION: Progestogens prevent preterm birth when used
      in singleton pregnancies for women with a prior preterm birth. In contrast,
      evidence suggests lack of effectiveness for multiple gestations. Evidence
      supporting all other uses is insufficient to guide clinical care. Overall,
      clinicians and patients lack longer-term information to understand whether
      intervention has the ultimately desired outcome of preventing morbidity and
      promoting normal childhood development.

PMID- 22955309
TI  - Overlapping compared with end-to-end repair of complete third-degree or fourth
      degree obstetric tears: three-year follow-up of a randomized controlled trial.
AB  - OBJECTIVE: To report on a 3-year follow-up of women who underwent overlapping
      repair of a complete third-degree or fourth-degree obstetric tear. METHODS:
      Primiparous women sustaining a complete third-degree or a fourth-degree tear of
      the perineum were randomized to a primary sphincter repair using either an end-to
      end or an overlapping surgical technique. At 1, 2, and 3 years, questionnaires on
      rates of flatal and fecal incontinence were mailed to participants. RESULTS: At 1
      year, women who underwent an end-to-end repair reported lower rates of flatal and
      fecal incontinence than women who had an overlapping repair. For flatal
      incontinence the rates were 31% compared with 56% (95% confidence interval for
      the rate difference 6-43%, P=.012). For fecal incontinence, the rates were 7%
      compared with 16% (95% confidence interval for the rate difference -4% to 21%,
      P=.17). The difference between the two methods of surgical repair had largely
      disappeared by the end of year 2. CONCLUSION: At 1-year follow-up, end-to-end
      repair of complete third-degree or fourth-degree obstetric anal sphincter tears
      is associated with significantly lower rates of anal incontinence when compared
      with overlapping repair. There is no long-term benefit associated with either
      technique over the other. CLINICAL TRIAL REGISTRATION: ISRCTN Register,
      http://isrctn.org, ISRCTNO 4149919. LEVEL OF EVIDENCE: I.

PMID- 22955310
TI  - Osteoporosis drug therapy strategies in the setting of disease-modifying agents
      for autoimmune disease.
AB  - The purpose of this systematic review is to evaluate the effects of methotrexate
      (MTX) and tumor necrosis factor-alpha (TNF-alpha) inhibitors on bone mineral
      properties in the clinical literature. A systematic review of the literature
      identifying relevant case reports, population-based studies, cohort studies, case
      control studies, and randomized controlled trials in Pubmed and Web of Science
      databases from inception to December 31, 2011 was conducted. The following
      keywords were used: "bone turnover," "bone mineral density," "TNF-alpha
      inhibitors," "infliximab," "adalimumab," "etanercept," and "MTX." The
      bibliographies of all retrieved studies were also reviewed to identify additional
      articles. Based on these results, a rational drug therapy strategy was suggested
      for treating osteoporosis in patients with inflammatory disease. MTX and TNF
      alpha inhibitors do not appear to have an adverse effect on BMD in patients with
      inflammatory disease. Their negative effects on BMD and bone turnover in pre
      clinical models appear to be outweighed by their anti-disease effects in clinical
      studies. Treatment with MTX or TNF-alpha inhibitors has no adverse effect on BMD
      in patients with inflammatory disease. Future studies will focus on developing
      optimal drug strategies when combining DMARDs with anti-osteoporotic agents in
      this patient population.

PMID- 22955311
TI  - The relationship between obesity and the increase in serum 25(OH)D levels in
      response to vitamin D supplementation.
AB  - This study examines the relationship between obesity and the increase in serum
      25(OH)D levels in response to vitamin D supplementation among adults with
      baseline serum 25(OH)D levels<50 nmol/L. This study revealed that the increase in
      serum 25(OH)D in response to vitamin D supplementation was higher in lean
      subjects as compared to obese subjects. INTRODUCTION: Serum 25(OH)D is lower
      among obese than non-obese. This study examines the relationship between obesity
      and the increase in serum 25(OH)D in response to vitamin D supplementation in a
      large sample of adults with baseline serum 25(OH)D<50 nmol/L, relatively long
      average treatment duration and large average daily cholecalciferol. METHODS: The
      computerized database of the Clalit Health Services, which the largest nonprofit
      health maintenance organization in Israel, was retrospectively searched for all
      subjects aged>=20 years who performed serum 25(OH)D test in 2011. Subjects with
      more than one test at different occasions in 2011 were identified and were
      included if the result of the first test was <50 nmol/L, and were treated with
      cholecalciferol between the first and the last test in 2011 (n=16,540 subjects).
      RESULTS: The mean increase in serum 25(OH)D level after treatment was 28.7 (95%
      confidence interval (CI), 28.0-29.4) nmol/L, 23.6 (23.0-24.2) nmol/L, and 20.1
      (19.6-20.6) nmol/L in subject with BMI of <25, 25-29.9, and >=30 kg/m2,
      respectively (P<0.001). The results were similar after adjustment for the
      potential confounders. Similarly, the proportion of subjects who achieved serum
      25(OH)D>=50 nmol/L after treatment was inversely associated with BMI; 65.1, 58.3,
      and 49.1% for BMI of <25, 25-29.9, and >=30 kg/m2, respectively. Compared to BMI
      of >=30 kg/m2, the adjusted odds ratio for achieving levels of >=50 nmol/L were
      2.12 (95 % CI, 1.94-2.31) and 1.42 (1.31-1.54) for BMI of <25 kg/m2, and BMI of
      25-29.9 kg/m2, respectively. CONCLUSIONS: BMI is inversely associated with the
      increase in serum 25(OH)D levels in response to vitamin D supplementation.

PMID- 22955312
TI  - DFT study of coverage-depended adsorption of NH3 on TiO2-B (100) surface.
AB  - A previous study showed that TiO(2)-B (100) surface is very unique. It is
      characterised by high activity and a loose structure. In this study, we studied
      the adsorption of ammonia on TiO(2)-B (100) surface at coverages ranging from 1/6
      ML to 1 ML using ab initio density functional calculations. We also investigated
      the adsorption of an isolated ammonia molecule on TiO(2)-B (001) surface to
      compare the different activities of TiO(2)-B (100) and (001) surfaces towards
      NH(3). The results showed that the TiO(2)-B (100) surface is more reactive
      towards NH(3) molecule than TiO(2)-B (001) surface, and the Lewis acid site on
      TiO(2)-B (100) surface is more acidic. The decrease rate of the average molecular
      adsorption energy of NH(3) with coverage on TiO(2)-B (100) surface is
      substantially lower than that on a rutile (011) surface above 1/2 ML coverage due
      to the open structure of TiO(2)-B (100) surface. The average molecular adsorption
      energy shows a linear dependence on the coverage of y = 111.0 - 36.3x on TiO(2)-B
      (100) surface. The possibility of NH(3) molecule onto the Ti(5c) site is nearly
      equal to forming a dimer with adsorbed NH(3) on TiO(2)-B (100) surface at 5/6 ML
      coverage.

PMID- 22955313
TI  - BLT1-dependent alveolar recruitment of CD4(+)CD25(+) Foxp3(+) regulatory T cells
      is important for resolution of acute lung injury.
AB  - RATIONALE: Recent study has demonstrated that CD4(+)CD25(+)Foxp3(+) regulatory T
      cells (Tregs) present in bronchoalveolar lavage fluid (BALF) contribute to the
      resolution of an experimental acute lung injury (ALI). However, the molecular
      mechanism underlying the alveolar recruitment of Treg remains unclear.
      OBJECTIVES: To determine the role of BLT1, a chemotactic receptor for leukotriene
      B4 (LTB4), in Treg recruitment to BALF of LPS-induced ALI. METHODS: We examined
      BLT1 expression in mouse and human Tregs and evaluated its role in mediating Treg
      migration in vitro and in vivo. MEASUREMENTS AND MAIN RESULTS: We found that BLT1
      expression was strongly up-regulated in Tregs on activation, and that BLT1
      mediated the migration of activated, but not resting, Tregs toward LTB4 in vitro.
      LTB4 levels were persistently elevated in BALF of LPS-induced ALI. Blockade of
      LTB4-BLT1 pathway by administrating antagonists 1 day after LPS exposure
      significantly decreased BALF Treg numbers and impaired resolution of ALI
      characterized by persistent BALF protein, neutrophilic infiltrates, and elevated
      proinflammatory cytokines. Furthermore, there were significantly less BLT1(-/-)
      Tregs than wild-type Tregs migrating to BALF of LPS-exposed recipient Rag-1(-/-)
      mice after adoptive transfer (point estimate 299.73; 95% confidence interval,
      255.77-343.69; P < 0.00001), and the impaired alveolar recruitment of BLT1(-/-)
      Tregs caused the inability to restore the resolution of ALI. CONCLUSIONS: Our
      findings reveal a novel antiinflammatory role of BLT1 in the resolution of ALI by
      mediating the alveolar recruitment of Tregs, and indicate that therapies aimed at
      interrupting the LTB4-BLT1 pathway after ALI onset could be harmful to the
      resolution of ALI.

PMID- 22955314
TI  - Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for
      lung gene therapy.
AB  - RATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling
      gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF),
      has led to the assessment of a lentiviral vector (simian immunodeficiency virus
      [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES:
      To place this vector onto a translational pathway to the clinic by addressing
      some key milestones that have to be achieved. METHODS: F/HN-SIV transduction
      efficiency, duration of expression, and toxicity were assessed in mice. In
      addition, F/HN-SIV was assessed in differentiated human air-liquid interface
      cultures, primary human nasal epithelial cells, and human and sheep lung slices.
      MEASUREMENTS AND MAIN RESULTS: A single dose produces lung expression for the
      lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve
      transduction. Repeated daily administration leads to a dose-related increase in
      gene expression. Repeated monthly administration to mouse lower airways is
      feasible without loss of gene expression. There is no evidence of chronic
      toxicity during a 2-year study period. F/HN-SIV leads to persistent gene
      expression in human differentiated airway cultures and human lung slices and
      transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS:
      The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene
      therapy for several diseases including CF. We are now undertaking the necessary
      refinements to progress this vector into clinical trials.

PMID- 22955315
TI  - Allostatic load biomarkers and asthma in adolescents.
AB  - RATIONALE: Allostatic load (AL), a novel measure of the physiologically
      dysregulated response of the body to stress, represents a biomarker of chronic
      stress exposure. OBJECTIVES: To determine whether preadolescent children with
      high AL are more susceptible to asthma as adolescents. METHODS: This was a
      prospective evaluation of children recruited at 7 to 10 years of age in the
      nested case-control arm of the Study of Asthma, Genes and Environment and
      followed until 11 to 14 years of age. AL was measured using eight biomarkers:
      fasting glucose, total cholesterol, high-density lipoprotein cholesterol,
      dehydroepiandrosterone sulfate, cortisol, systolic and diastolic blood pressure,
      and waist-to-hip ratio. AL, created from the sum of biomarkers in a high-risk
      quartile, was related to prevalence and incidence of asthma using logistic
      regression. MEASUREMENTS AND MAIN RESULTS: Among 352 participants followed until
      11 to 14 years of age, prevalent asthma was four times more likely in boys with
      high (>3) versus low (<=2) AL after adjusting for current asthma/atopy, age,
      ethnicity, parental history of asthma, and overweight status. Similar results
      were observed in the analysis of new-onset asthma in boys (adjusted odds ratio,
      4.35; 95% confidence interval, 1.19-15.9). In girls, there were no associations
      between AL and asthma. In the analysis of a subset of biomarkers, combinations of
      total cholesterol, glucose, and cortisol were associated with similar or greater
      risk of asthma prevalence or onset in boys. CONCLUSIONS: AL and its biomarkers
      are associated with an increased likelihood of asthma in adolescent boys. The
      observed association between AL and asthma may be attributable to a combined
      subset of AL biomarkers.

PMID- 22955316
TI  - Predictive value of recent QuantiFERON conversion for tuberculosis disease in
      adolescents.
AB  - RATIONALE: Conversions and reversions occur with IFN-gamma release assay (IGRA)
      serial testing, as with the tuberculin skin test (TST). Recent TST conversion is
      associated with an established risk of developing tuberculosis (TB) disease, but
      the risk associated with recent IGRA conversions is unknown. OBJECTIVES: To
      compare the incidence rate of TB disease after recent QuantiFERON TB Gold In-Tube
      (QFT) conversion compared with nonconverters. METHODS: Adolescents with converted
      IGRA status (QFT converters [n = 534]) and randomly chosen adolescents whose IGRA
      status had remained negative over a period of 2 years (QFT nonconverters [n =
      629]) were identified in a cohort study of TB infection and disease. Subsequent
      TB disease incidence was compared between the two groups. MEASUREMENTS AND MAIN
      RESULTS: For QFT converters, the TB incidence rate (all cases) was 1.46 cases per
      100 person-years (95% confidence interval [CI], 0.82-2.39), and the cumulative
      incidence was 2.8% (95% CI, 1.58-4.59). A significantly lower TB incidence rate
      (0.17 cases per 100 person-yr [95% CI, 0.02-0.62]) and cumulative incidence
      (0.32% [95% CI, 0.03-1.14]) was observed for QFT nonconverters. The incidence
      rate ratio was 8.54 (95% CI, 2.51-29.13) for all cases of TB and 9.1 (95% CI,
      1.65-50.36) for protocol-defined TB. CONCLUSIONS: Recent QFT conversion was
      indicative of an approximately eight fold higher risk of progression to TB
      disease (compared with nonconverters) within 2 years of conversion in a cohort of
      adolescents in a high-TB burden population.

PMID- 22955317
TI  - CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical
      relevance in non-small cell lung cancer.
AB  - RATIONALE: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of
      myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their
      clinical relevance remains unclear. OBJECTIVES: To identify subtypes of myeloid
      derived suppressor cells in patients with non-small cell lung cancer (NSCLC) and
      their clinical relevance. METHODS: CD11b(+)CD14(-) and CD11b(+)CD14(+) cells,
      determined and phenotyped by fluorescence-activated cell sorter analysis, in the
      peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with
      advanced NSCLC were correlated with clinical data. T-cell activation in response
      to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate
      succinimidyl ester (CFSE) staining and ELISA analysis of IFN-gamma. The
      percentage of CD11b(+)CD14(+)S100A9(+) cells in PBMCs was correlated with and
      tested as a predictor for treatment response in a cohort of patients
      prospectively receiving first-line cisplatin-based chemotherapy. MEASUREMENTS AND
      MAIN RESULTS: Patients with NSCLC had a significantly higher ratio of
      CD11b(+)CD14(+) cells than healthy subjects, which was correlated with poor
      performance status and poor response to chemotherapy. The depletion of these
      cells in the PBMC reversed the suppression of CD8(+) and CD4(+) T cells. Isolated
      CD11b(+)CD14(+) cells suppressed CD8(+) T-cell proliferation and IFN-gamma
      production, and the former effect was attenuated by the inducible nitric oxide
      synthase (iNOS) inhibitor aminoguanidine hydrochloride, arginase inhibitor N
      hydroxy-nor-l-arginine (nor-NOHA), and blocking antibodies for IL-4Ralpha(+) and
      IL-10. CD11b(+)CD14(+) cells were monocyte-like, expressing CD33(+), CD15(-/low),
      IL-4Ralpha(+), and S100A9(+) and producing iNOS, arginase, and several cytokines.
      The ratio of S100A9(+) cells positively correlated with the suppressive ability
      of the CD11b(+)CD14(+) cells, was associated with poor response to chemotherapy,
      and predicted shorter progression-free survival. CONCLUSIONS: CD14(+)S100A9(+)
      inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs,
      which suppress T cells by arginase, iNOS, and the IL-13/IL-4Ralpha axis. The
      amount of these inflammatory monocytes is associated with poor response to
      chemotherapy. Clinical trial registered with www.clinicaltrials.gov (NCT
      01204307).

PMID- 22955318
TI  - Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary
      arterial hypertension.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by
      vasoconstriction and vascular remodeling. Recent studies have revealed that
      immune and inflammatory responses play a crucial role in pathogenesis of
      idiopathic PAH. OBJECTIVES: To systematically evaluate the number and cross
      sectional distribution of inflammatory cells in different sizes of pulmonary
      arteries from explanted lungs of patients with idiopathic PAH versus healthy
      donor lungs and to demonstrate functional relevance by blocking stromal-derived
      factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary
      hypertension in rats. METHODS: Immunohistochemistry was performed on lung tissue
      sections from patients with idiopathic PAH and healthy donors. All positively
      stained cells in whole-lung tissue sections, surrounding the vessels, and in the
      different compartments of the vessels were counted. To study the effects of
      blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were
      treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration.
      MEASUREMENTS AND MAIN RESULTS: We found a significant increase of the
      perivascular number of macrophages (CD68(+)), macrophages/monocytes (CD14(+)),
      mast cells (toluidine blue(+)), dendritic cells (CD209(+)), T cells (CD3(+)),
      cytotoxic T cells (CD8(+)), and helper T cells (CD4(+)) in vessels of idiopathic
      PAH lungs compared with control subjects. FoxP3(+) mononuclear cells were
      significantly decreased. In the monocrotaline model, the NOX-A12-induced
      reduction of mast cells, CD68(+) macrophages, and CD3(+) T cells was associated
      with improvement of hemodynamics and pulmonary vascular remodeling. CONCLUSIONS:
      Our findings reveal altered perivascular inflammatory cell infiltration in
      pulmonary vascular lesions of patients with idiopathic pulmonary arterial
      hypertension. Targeting attraction of inflammatory cells by blocking stromal
      derived factor-1 may be a novel approach for treatment of PAH.

PMID- 22955320
TI  - Selective deposition of Pt onto supported metal clusters for fuel cell
      electrocatalysts.
AB  - We report a new method for deposition of Pt on a metal core to develop real
      electrocatalysts with significantly reduced amounts of expensive Pt as well as
      enhanced activity for oxygen reduction reaction. Ru and Pd have different crystal
      structures and modify the electronic structure of Pt to a different extent
      (shifts in d-band center). They were chosen as core materials to examine whether
      hydroquinone dissolved in ethanol can be used to deposit additional Pt atoms onto
      preformed core nanoparticles, and whether the modified d-character of Pt on
      different host metals can result in the enhanced ORR activity. The
      physicochemical characteristics of Pd-Pt and Ru-Pt core-shell nanoparticles are
      investigated. The core-shell structure was identified through a combination of
      experimental methods, employing electron microscopy, electrochemical
      measurements, and synchrotron X-ray measurements such as powder X-ray
      diffraction, X-ray absorption fine structure, and X-ray photoelectron
      spectroscopy. The hydroquinone reduction method proved to be an excellent route
      for the epitaxial growth of a Pt shell on the metal cores, leading to enhanced
      ORR activities.

PMID- 22955319
TI  - Airway epithelial miRNA expression is altered in asthma.
AB  - RATIONALE: Changes in airway epithelial cell differentiation, driven in part by
      IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation
      in many systems and could contribute to epithelial abnormalities in asthma.
      OBJECTIVES: To determine whether airway epithelial miRNA expression is altered in
      asthma and identify IL-13-regulated miRNAs. METHODS: We used miRNA microarrays to
      analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma
      before and after inhaled corticosteroids, 19 steroid-using subjects with asthma,
      and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on
      cultured bronchial epithelial cells. We used quantitative polymerase chain
      reaction to confirm selected microarray results. MEASUREMENTS AND MAIN RESULTS:
      Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal
      pattern of bronchial epithelial miRNA expression by microarray analysis. Compared
      with control subjects, 217 miRNAs were differentially expressed in steroid-naive
      subjects with asthma and 200 in steroid-using subjects with asthma (false
      discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects
      on miRNA expression in steroid-naive asthma, inducing a statistically significant
      (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis
      confirmed differential expression of 22 miRNAs that were highly differentially
      expressed by microarrays. IL-13 stimulation recapitulated changes in many
      differentially expressed miRNAs, including four members of the miR-34/449 family,
      and these changes in miR-34/449 family members were resistant to corticosteroids.
      CONCLUSIONS: Dramatic alterations of airway epithelial cell miRNA levels are a
      common feature of asthma. These alterations are only modestly corrected by
      inhaled corticosteroids. IL-13 effects may account for some of these alterations,
      including repression of miR-34/449 family members that have established roles in
      airway epithelial cell differentiation. Clinical trial registered with
      www.clinicaltrials.gov (NCT 00595153).

PMID- 22955321
TI  - Maternal chromosome 4 heterodisomy/isodisomy and Bbeta chain Trp323X mutation
      resulting in severe hypodysfibrinogenaemia.
AB  - We report a rare case of congenital hypodysfibrinogenaemia due to maternal
      uniparental disomy of chromosome 4 (mat UPD 4) and a maternally inherited novel
      nonsense mutation Trp323X in the fibrinogen Bbeta chain (FGB) gene. Western blot
      analysis of patient's plasma revealed an abnormal fibrinogen which consisted of
      truncated Bbeta chain and normal Aalpha and gamma chains. Patient's clinical
      history and laboratory evidence are presented. Microsatellite genotyping analysis
      revealed a mixed nature of heterodisomy and isodisomy along chromosome 4. High
      density SNP genotyping array analysis further confirmed the mat UPD 4 and defined
      two segments of chromosome 4 (4pter-p15.33 and 4q31.21-4q32.3) as maternal
      isodisomy (iUPD4) and the remaining regions as maternal heterodisomy (hUPD4),
      with the  FGB  gene carrying the mutation resided in the iUPD4 region on the long
      (q) arm. It was predicted that the segmental nature of iUPD and hUPD was caused
      by three recombination events at positions around 167.96 cM, 145.51 cM and 14.40
      cM on chromosome 4 followed by a meiosis I non-disjunction. This case is
      clinically and molecularly unique and offers an opportunity for understanding
      novel mechanisms of congenital hypodysfibrinogenaemia associated with complex UPD
      and fibrinogen secretion.

PMID- 22955322
TI  - Stress-induced activation of decomposition of organic explosives: a simple way to
      understand.
AB  - We provide a very simply way to understand the stress-induced activation of
      decomposition of organic explosives by taking the simplest explosive molecule
      nitromethane (NM) as a prototype and constraining one or two NM molecules in a
      shell to represent the condensed phrase of NM against the stress caused by
      tension and compression, sliding and rotational shear, and imperfection. The
      results show that the stress loaded on NM molecule can always reduce the barriers
      of its decomposition. We think the origin of this stress-induced activation is
      due to the increased repulsive intra- and/or inter- molecular interaction
      potentials in explosives resulted from the stress, whose release is positive to
      accelerate the decomposition. Besides, by these models, we can understand that
      the explosives in gaseous state are easier to analyze than those in condensed
      state and the voids in condensed explosives make them more sensitive to external
      stimuli relative to the perfect crystals.

PMID- 22955323
TI  - Highly reproducible low temperature scanning tunneling microscopy and
      spectroscopy with in situ prepared tips.
AB  - An in situ tip preparation procedure compatible with ultra-low temperature and
      high magnetic field scanning tunneling microscopes is presented. This procedure
      does not require additional preparation techniques such as thermal annealing or
      ion milling. It relies on the local electric-field-induced deposition of material
      from the tip onto the studied surface. Subsequently, repeated indentations are
      performed onto the sputtered cluster to mechanically anneal the tip apex and thus
      to ensure the stability of the tip. The efficiency of this method is confirmed by
      comparing the topography and spectroscopy data acquired with either unprepared or
      in situ prepared tips on epitaxial graphene grown on Ru (0001). We demonstrate
      that the use of in situ prepared tips increases the stability of the scanning
      tunneling images and the reproducibility of the spectroscopic measurements.

PMID- 22955324
TI  - Element discrimination in a hexagonal boron nitride nanosheet by aberration
      corrected transmission electron microscopy.
AB  - Boron nitride nanosheets prepared by an exfoliation technique were observed by
      aberration corrected transmission electron microscopy at 300 kV acceleration
      voltage. Single boron and nitrogen atoms in a monolayer region were imaged with
      different image contrast; a boron atom gave 16% less intensity reduction than a
      nitrogen atom. The number of atoms at each hexagonal ring site was determined by
      the image intensity that changed discretely with a 0.25-0.30 intensity
      difference. A double BN sheet was found to have a boron vacancy layer, and a
      triple BN layer has also a boron deficient layer on the incident surface
      resulting from the electron beam thinning process. The high sensitivity for
      atomic species was achieved by the high resolution and a small information limit
      due to the use of a cold field emission electron source.

PMID- 22955325
TI  - Characterization of a novel xylanase from Armillaria gemina and its
      immobilization onto SiO2 nanoparticles.
AB  - Enhanced catalytic activities of different lignocellulases were obtained from
      Armillaria gemina under statistically optimized parameters using a jar fermenter.
      This strain showed maximum xylanase, endoglucanase, cellobiohydrolase, and beta
      glucosidase activities of 1,270, 146, 34, and 15 U mL(-1), respectively. Purified
      A. gemina xylanase (AgXyl) has the highest catalytic efficiency (k (cat)/K (m) =
      1,440 mg mL(-1) s(-1)) ever reported for any fungal xylanase, highlighting the
      significance of the current study. We covalently immobilized the crude xylanase
      preparation onto functionalized silicon oxide nanoparticles, achieving 117 %
      immobilization efficiency. Further immobilization caused a shift in the optimal
      pH and temperature, along with a fourfold improvement in the half-life of crude
      AgXyl. Immobilized AgXyl gave 37.8 % higher production of xylooligosaccharides
      compared to free enzyme. After 17 cycles, the immobilized enzyme retained 92 % of
      the original activity, demonstrating its potential for the synthesis of
      xylooligosaccharides in industrial applications.

PMID- 22955328
TI  - Structural, electronic and acid/base properties of [Ru(bpy(OH)2)3]2+ (bpy(OH)2 =
      4,4'-dihydroxy-2,2'-bipyridine).
AB  - We have synthesized the complex [Ru(bpy(OH)(2))(3)](2+) (bpy(OH)(2) = 4,4'
      dihydroxy-2,2'-bipyridine) containing ligands that can be readily deprotonated.
      Both experimental and computational techniques were utilized to perform a
      thorough analysis of the structural and electronic properties of the complex in
      both the protonated and deprotonated state. The complex [Ru(bpy(OMe)(2))(3)](2+)
      (bpy(OMe)(2) = 4,4'-dimethoxy-2,2'-bipyridine) was also synthesized and studied,
      because the bpy(OMe)(2) ligand has electron-donating properties like bpy(OH)(2),
      but does not contain deprotonatable groups. Cyclic voltammetry of
      [Ru(bpy(OH)(2))(3)](2+) yields a reversible Ru(III/II) wave that shifts 1.43 V to
      lower energy upon deprotonation of the complex. UV/Visible absorbance
      spectroscopy reveals several Metal-to-Ligand Charge Transfer (MLCT) transitions
      that shift to lower energy upon deprotonation of the complex. This observation is
      in contrast to mixed-ligand systems containing deprotonatable groups, such as
      [Ru(bpy)(2)(bpy(OH)(2))](2+) (bpy = 2,2'-bipyridine) that demonstrate different
      types of electronic transitions assigned as mixed Metal-Ligand to Ligand Charge
      Transfer (MLLCT). The more symmetrical nature of the tris-bpy(OH)(2) complex most
      likely prevents the metal molecular orbitals from significantly mixing with the
      molecular orbitals of the deprotonated ligand. Luminescence studies were carried
      out on [Ru(bpy(OH)(2))(3)](2+) and reveal a shift to lower energy and quenching
      of the excited state upon deprotonation in accordance with the energy gap law.

PMID- 22955326
TI  - Immune response and immunopathology during toxoplasmosis.
AB  - Toxoplasma gondii is a protozoan parasite of medical and veterinary significance
      that is able to infect any warm-blooded vertebrate host. In addition to its
      importance to public health, several inherent features of the biology of T.
      gondii have made it an important model organism to study host-pathogen
      interactions. One factor is the genetic tractability of the parasite, which
      allows studies on the microbial factors that affect virulence and allows the
      development of tools that facilitate immune studies. Additionally, mice are
      natural hosts for T. gondii, and the availability of numerous reagents to study
      the murine immune system makes this an ideal experimental system to understand
      the functions of cytokines and effector mechanisms involved in immunity to
      intracellular microorganisms. In this article, we will review current knowledge
      of the innate and adaptive immune responses required for resistance to
      toxoplasmosis, the events that lead to the development of immunopathology, and
      the natural regulatory mechanisms that limit excessive inflammation during this
      infection.

PMID- 22955329
TI  - Immunoglobulin heavy/light chain ratios improve paraprotein detection and
      monitoring, identify residual disease and correlate with survival in multiple
      myeloma patients.
AB  - The novel heavy/light chain (HLC) assay was used for the detection and
      measurement of monoclonal immunoglobulins, response evaluation and
      prognostication. This test allows identification and quantification of the
      different light chain types of each immunoglobulin class (for example, IgGkappa
      and IgGlambda) and enables calculation of ratios of monoclonal/polyclonal
      immunoglobulin (HLC ratio). Sequential sera of 156 patients with IgG or IgA
      myeloma started on first-line therapy and followed for a median of 46.1 months
      were analyzed. Results were compared with those obtained with conventional
      techniques (serum protein electrophoresis (SPEP), immunofixation electrophoresis
      (IFE), nephelometry (NEPH), and the free light chain test (FLC)). Our data show
      that the HLC assay allowed quantification of monoclonal proteins not accurately
      measurable by SPEP or NEPH. When both HLC and FLC testing were applied for
      response assessment, clonal excess was noted in 14/31 patients with complete
      response (CR). HLC ratio indicated presence of disease in 8/31 patients who
      achieved CR and, in sequential studies indicated evolving relapse in three
      patients before IFE became positive. Highly abnormal HLC ratios at presentation
      were significantly associated with shorter overall survival (40.5 months vs
      median not reached, P=0.016). Multivariate analysis revealed HLC ratio (P=0.03)
      and beta(2)-microglobulin (P<0.01) as independent risk factors for survival.

PMID- 22955330
TI  - Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for
      chronic lymphocytic leukemia: prognostic model to predict outcome.
AB  - Chronic lymphocytic leukemia (CLL) remains incurable with chemoimmunotherapy, and
      allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential
      for cure. We assessed the outcomes of 108 CLL patients undergoing first
      allogeneic HSCTs, 76 with reduced-intensity (RIC) and 32 with myeloablative
      conditioning (MAC) between 1998 and 2009 at Dana-Farber Cancer Institute. With
      median follow-up of 5.9 years in surviving patients, the 5-year overall survival
      (OS) for the entire cohort is 63% for RIC regimens and 49% for MAC regimens
      (P=0.18). The risk of death declined significantly starting in 2004, and we found
      that 5-year OS for HSCT between 2004 and 2009 was 83% for RIC regimens compared
      with 47% for MAC regimens (P=0.003). For RIC transplantation, we developed a
      prognostic model based on predictors of progression-free survival (PFS),
      specifically remission status, lactate dehydrogenase, comorbidity score and
      lymphocyte count, and found 5-year PFS to be 83% for Score 0, 63% for Score 1,
      24% for Score 2 and 6% for Score >=3 (P<0.0001). We conclude that RIC HSCT for
      CLL in the current era is associated with excellent long-term PFS and OS, and, as
      potentially curative therapy, should be considered early in the disease course of
      relapsed high-risk CLL patients.

PMID- 22955331
TI  - Treatment of pertrochanteric fractures (OTA 31-A1 and A2): long versus short
      cephalomedullary nailing.
AB  - OBJECTIVES: To retrospectively compare the clinical outcomes in patients with
      pertrochanteric femur fractures without subtrochanteric extension (OTA 31-A1 and
      A2) after treatment with short or long cephalomedullary nails. DESIGN:
      Retrospective study. SETTING: Academic level I trauma center. PATIENTS: Two
      hundred eighty three adult patients presenting with simple or multifragmentary
      pertrochanteric femur fractures (OTA 31-A1 and A2) between 2004 and 2009
      qualified for inclusion in this study. INTERVENTION: One hundred patients were
      treated with a short cephalomedullary nail and 183 with a long cephalomedullary
      nail. MAIN OUTCOME MEASUREMENTS: Patient demographics and medical comorbidities
      were recorded for each patient via an electronic medical record. Treatment
      related variables including the American Society of Anesthesiologists (ASA)
      score, duration of surgery, volume of intraoperative blood loss, need for blood
      products, treatment-related complications, and mortality were recorded and
      compared between the short and long nail groups. RESULTS: There were no
      significant difference between treatment modalities, complication, and
      reoperation rates for the 2 groups. Treatment with a long nail resulted in subtle
      increases in procedure time and blood loss. CONCLUSIONS: No differences in the
      union and complication rates between the 2 groups were identified, suggesting
      that long nails offer no advantage compared with short nails for stabilizing
      simple and multifragmentary pertrochanteric femur fractures without
      subtrochanteric extension (OTA 31-A1 and A2). LEVEL OF EVIDENCE: Therapeutic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22955332
TI  - Investigation of multiligamentous knee injury patterns with associated injuries
      presenting at a level I trauma center.
AB  - OBJECTIVES: To characterize multiligamentous knee injury patterns and describe
      associated morbidities. DESIGN: Retrospective. SETTING: Level I trauma center.
      PATIENTS: One hundred two patients (106 knees) with multiligamentous knee
      injuries and/or dislocations from 2000 through 2008. Subgroup of 82 knees with
      appropriate magnetic resonance images available assessed for ligamentous injury
      patterns. INTERVENTION: Data obtained from medical records for 106 knees. MAIN
      OUTCOME MEASUREMENTS: Presence of arterial injuries, nerve injuries, associated
      fracture patterns, and whole-body morbidities. RESULTS: The most common (43%)
      injury pattern was a combined disruption of the anterior cruciate ligament,
      posterior cruciate ligament, and posterolateral corner. Twenty-five percent of
      knees had associated ipsilateral tibial plateau fractures, and 19% had associated
      ipsilateral femoral fractures. Peroneal nerve injury occurred in 25% of knees,
      arterial injury in 21%, and compartment syndrome in 16%. An intra-abdominal
      injury was present in 13% of patients, a severe closed head injury in 10%, and a
      symptomatic pulmonary embolism in 5%. CONCLUSIONS: Nearly half the
      multiligamentous knee injuries involved the anterior cruciate ligament, posterior
      cruciate ligament, and posterolateral corner; one-fourth had associated
      ipsilateral tibial plateau fractures. The incidence of peroneal nerve injury
      (25%) was higher than previously reported (20%), whereas the incidence of
      arterial injury (21%) was comparable to previous reports (19%). Posterolateral
      corner injuries were more prevalent than previously reported and were highly
      associated with peroneal nerve injury. We found a substantial incidence of
      associated morbidities of the whole body. Multiligamentous knee injuries are a
      marker of concomitant trauma and should be closely evaluated at presentation and
      during the hospital course to allow for early intervention for life- or limb
      threatening comorbidities.

PMID- 22955327
TI  - Involvement of inflammatory factors in pancreatic carcinogenesis and preventive
      effects of anti-inflammatory agents.
AB  - Chronic inflammation is known to be a risk for many cancers, including pancreatic
      cancer. Heavy alcohol drinking and cigarette smoking are major causes of
      pancreatitis, and epidemiological studies have shown that smoking and chronic
      pancreatitis are risk factors for pancreatic cancer. Meanwhile, inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are elevated in pancreatitis
      and pancreatic cancer tissues in humans and in animal models. Selective
      inhibitors of iNOS and COX-2 suppress pancreatic cancer development in a chemical
      carcinogenesis model of hamsters treated with N-nitrosobis(2-oxopropyl)amine
      (BOP). In addition, hyperlipidemia, obesity, and type II diabetes are also
      suggested to be associated with chronic inflammation in the pancreas and involved
      in pancreatic cancer development. We have shown that a high-fat diet increased
      pancreatic cancer development in BOP-treated hamsters, along with aggravation of
      hyperlipidemia, severe fatty infiltration, and increased expression of adipokines
      and inflammatory factors in the pancreas. Of note, fatty pancreas has been
      observed in obese and/or diabetic cases in humans. Preventive effects of anti
      hyperlipidemic/anti-diabetic agents on pancreatic cancer have also been shown in
      humans and animals. Taking this evidence into consideration, modulation of
      inflammatory factors by anti-inflammatory agents will provide useful data for
      prevention of pancreatic cancer.

PMID- 22955333
TI  - Effect of computerized tomography on classification and treatment plan for
      patellar fractures.
AB  - OBJECTIVE: To evaluate the impact of computerized tomography (CT) scan on both
      fracture classification and surgical planning of patellar fractures. DESIGN:
      Prospective study. SETTING: Academic level I trauma center. PATIENTS AND METHODS:
      Four fellowship-trained orthopaedic trauma surgeons analyzed radiographs of 41
      patellar fractures. Each fracture was classified (OTA/AO classification), and a
      treatment plan was developed using plain radiographs alone. The process was
      repeated (4-6 weeks later) with addition of CT scan. After 12 months, the 2-step
      analysis was repeated and interobserver reliability and intraobserver
      reproducibility were assessed. RESULTS: Suboptimal intra- and interobserver
      reliability was found for the surgical plan and classification using the OTA/AO
      system, despite the addition of a CT scan. After addition of CT, reviewers
      modified the classification in 66% of cases and treatment plan in 49%. CT
      frequently demonstrated a distinctive and severely comminuted distal pole
      fracture; this fracture pattern was present in 88% of cases and was unappreciated
      on plain radiographs in 44% of those cases. This pattern is unaccounted for by
      the present OTA/AO classification. CONCLUSIONS: CT facilitates improved
      delineation of patellar fracture patterns. Understanding the distal pole fracture
      pattern is fundamental in choosing a fixation construct. A fracture-specific
      classification system, based on CT scans, should be developed.

PMID- 22955334
TI  - Diagnosis of femoral neck fracture associated with femoral shaft fracture:
      blinded comparison of computed tomography and plain radiography.
AB  - OBJECTIVE: Femoral neck fractures that are associated with femoral shaft
      fractures have historically been associated with high rates of missed diagnosis.
      Despite the potentially serious consequences of a missed femoral neck fracture,
      little work has been conducted to rigorously evaluate the ability of commonly
      used imaging studies to detect such fractures. Our hypothesis was that axial-view
      computed tomography is superior to plain radiography at detecting femoral neck
      fractures. DESIGN: Blinded assessment of a randomized image set that included
      axial-view computed tomographic scans of the pelvis, anteroposterior-view
      radiographs of the pelvis, and anteroposterior-view radiographs of the femur.
      SETTING: Academic trauma center. PATIENTS: Twenty-eight patients who had femoral
      shaft fractures with femoral neck fractures and 60 patients who had femoral shaft
      fractures without femoral neck fractures. INTERVENTION: Images that were stripped
      of demographic data were independently viewed in random order on computer
      workstations by 5 trauma fellowship-trained orthopaedic surgeons who were blinded
      to treatment and diagnosis. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity,
      positive post-test probability, and 1 minus negative post-test probability were
      calculated for diagnosing femoral neck fracture based on each image type.
      RESULTS: Interobserver reliability showed "substantial agreement" (kappa > 0.65)
      for all imaging modalities, indicating that the surgeons had a high level of
      agreement. All 3 imaging sets had high specificity (>94%) and 1 minus negative
      post-test probability (>95%) but had poor sensitivity (<65%) and positive post
      test probability (<58%). False positives and false negatives were equally likely
      for all imaging modalities (P > 0.2). CONCLUSIONS: Plain radiography and computed
      tomography have rates of missed femoral neck fractures that are similar and
      substantial, with a sensitivity of only 56%-64%. Our data emphasize the
      importance of intraoperative and postoperative imaging in detecting nondisplaced
      femoral neck fractures in association with femoral shaft fractures.

PMID- 22955335
TI  - Analysis of retrograde femoral intramedullary nail placement through traumatic
      knee arthrotomies.
AB  - OBJECTIVES: To analyze the rate of postoperative infection after retrograde
      femoral nail placement in the setting of traumatic knee arthrotomy (KA). DESIGN:
      Retrospective. SETTING: Level-I trauma center. PATIENTS: A review of all adult
      femur fractures (N = 1748) treated with an intramedullary nail over a 10-year
      period identified 34 retrograde nails with traumatic KA as the study group and 23
      antegrade nails with traumatic KA as a control group. The retrograde femoral
      traumatic KA group was also compared with a 4:1 matched control group of 136
      patients with retrograde femoral nails without traumatic KA. INTERVENTION:
      Retrograde femoral nail placement with traumatic KA. MAIN OUTCOME MEASUREMENTS:
      Occurrence of postoperative infection. RESULTS: The traumatic KA groups treated
      with retrograde and antegrade femoral nails were similar across all recorded
      patient variables. No infections occurred in the retrograde traumatic KA group
      versus 1 infection (4.3%) in the antegrade traumatic KA group (P = 0.404). Four
      nonunions (11.8%) occurred in the retrograde traumatic KA group versus 1 nonunion
      (4.3%) in the antegrade traumatic KA group (P = 0.638). The matched control group
      of retrograde nails did not significantly differ when compared with the
      retrograde traumatic KA group for infection or nonunion (P = 1.000 and 0.261).
      CONCLUSIONS: This is the first study to investigate retrograde nail placement
      through traumatic KA with comparison to control groups, with no differences found
      in infection rates. Furthermore, no infections (knee or fracture) occurred in
      those patients who were treated using a retrograde femoral nail with traumatic
      KA. This study documents the relative safety associated with retrograde femoral
      nailing in the setting of a concurrent traumatic KA with surgical debridement.

PMID- 22955336
TI  - Reoperation rate after internal fixation of intertrochanteric femur fractures
      with the percutaneous compression plate: what are the risk factors?
AB  - OBJECTIVE: The aim was this study was to analyze the risk factors for reoperation
      after internal fixation of intertrochanteric fractures of the femur using the
      percutaneous compression plate (PCCP). DESIGN: This was a retrospective cohort
      study. SETTING: The study was conducted at the University Hospital. PATIENTS AND
      METHODS: Patients with intertrochanteric femur fractures who underwent internal
      fixation with a PCCP were included in this study. We investigated potential risk
      factors such as age, gender, body mass index, comorbidities of the patients
      (American Society of Anesthetist classification), type of fracture (AO/OTA
      classification), experience of the surgeons (in terms of the number of surgical
      procedures with the PCCP device), tip-apex distance (TAD), and operation time.
      The procedures were performed by 10 surgeons. Logistic regression was used to
      assess potential predictors for the need of reoperation. RESULTS: Of the 96
      patients with 96 intertrochanteric fractures, 8 underwent reoperation due to
      local complications (8.3%). The most frequent complication was complete or
      imminent cutting out of the upper cervical screw (N = 5; 5.2%). Five of the 8
      risk factors that were associated with reoperation in the initial univariable
      analyses with a P value of <0.20 were retained in a multivariable logistic
      regression model, including, age, body mass index, TAD, experience of the
      surgeons, and operation time. Of these, only the factor TAD proved to be a
      significant predictor for reoperation (P = 0.027, odds ratio = 1.089, 95%
      confidence interval 1.01-1.175). CONCLUSIONS: Our data show that the surgeon
      related risk factors (number of operations, operation time, TAD) seem to be more
      relevant for the reoperation rate after internal fixation with the PCCP device
      when compared with the patient-related risk factors. This finding indicates a
      substantial learning curve for this technically demanding procedure. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 22955337
TI  - The effect of transdermal nicotine on fracture healing in a rabbit model.
AB  - OBJECTIVE: Cigarette smoking inhibits fracture healing and places the patient at
      a higher risk of delayed union and nonunion. Nicotine has been implicated as the
      primary ingredient responsible for these effects. However, an analysis of current
      published investigations reveals conflicting data, with some evidence that
      nicotine alone does not significantly affect healing. We undertook an animal
      study of the effects of transdermal nicotine on fracture healing. METHODS: Twenty
      two adult male New Zealand white rabbits were randomly assigned to the nicotine
      group or the control group. A midshaft tibial osteotomy was performed on the left
      tibiae of all 22 rabbits. The nicotine rabbits were exposed using a 10.5-mg
      transdermal patch applied daily to the ear. Radiographs were obtained, and the
      area of fracture callus was assessed. Rabbits were euthanized at 21 days.
      Fractures were stressed to failure, and load/deformation curves were recorded.
      RESULTS: The average area of callus formation was greater in the control group (
      CONTROL: 0.158 cm, Nicotine: 0.124 cm), but the difference was not statistically
      significant (P = 0.30). There was a significant difference between the 2 groups
      for mean normalized torque to failure (Nicotine: 36% of nonfractured side,
      CONTROL: 69% of nonfractured side, P = 0.028). The control group mean normalized
      stiffness was significantly greater than that for the nicotine rabbits ( CONTROL:
      87%, Nicotine: 43%, P = 0.036). There were 3 nonunions in the nicotine group
      (27%) compared with none in the control group (P = 0.062). CONCLUSIONS: In a
      rabbit model of fracture healing, transdermal nicotine exposure resulted in
      decreased mechanical strength of healing fractures at 21 days and a higher rate
      of nonunion at 21 days compared with that of controls.

PMID- 22955338
TI  - Bone transport combined with locking bridge plate fixation for the treatment of
      tibial segmental defects: a report of 2 cases.
AB  - Segmental tibial bone loss, specifically in the setting of high-energy trauma,
      presents a challenging problem to the treating orthopaedic surgeon. These
      injuries are often complicated by tissue loss, poor wound healing, and infection.
      Many techniques of reconstruction have been advocated from bone grafting to bone
      transport. Transport can accomplished using Ilizarov frames, monolateral external
      fixators, and intramedullary devices. Although transport over an intramedullary
      device offers the advantage of rigidity and controlled alignment, many authors
      consider prolonged external fixation and history of pin tract infection to be
      contraindications to this technique. To our knowledge, bone segment transport
      used in combination with locking plate fixation has not been described for the
      treatment of tibial bone defects. We describe two cases of bone transport using a
      combination of locked plate fixation and a monolateral external fixation frame
      for large tibial bone defects. This technique allows for easy correction of
      length and alignment, stable fixation, facilitates quicker, and easier frame
      removal and also allows for compression of transported segment at the time of
      docking.

PMID- 22955339
TI  - Cancer incidence among Turkish, Chilean, and North African first-generation
      immigrants in Sweden compared with residents in the countries of origin and
      native Swedes.
AB  - We compared the incidence of cancer among Turkish, Chilean, and North African
      (NA) first-generation immigrants with residents in their countries of origin and
      native Swedes. The Swedish Family-Cancer Database was used to calculate age
      standardized incidence rates. We compared the age-standardized incidence rates
      for immigrants with those in the Cancer Incidence in Five Continents report. All
      cancer rates were decreased in Turks (men) and Chileans and increased in NAs
      compared with the residents in their countries of origin. The rates of stomach
      cancer in Chileans and lung cancer in Turkish men were decreased, whereas Turkish
      women had an increased rate of lung cancer. Furthermore, the rate of prostate
      cancer in Turks and NAs and nervous system tumors in NA men and Turkish women
      were increased. Chileans had higher rates of stomach and testicular cancers and
      lower rates of colon cancer, nervous system tumors, and non-Hodgkin's lymphoma
      compared with Swedes. Higher rates of male lung cancer and female thyroid cancer,
      and lower rates of male rectal and kidney cancers and nervous system tumors, and
      female stomach and colon cancers were observed among Turks compared with Swedes.
      The differences observed in all-cancer rates among immigrants were mostly
      attributable to decreased rates of stomach and lung cancers or an increased rate
      of prostate cancer after migration. We observed increased rates of colon, breast,
      and nervous system cancers after migration, whereas the rates of testicular,
      kidney and thyroid cancers, and non-Hodgkin's lymphoma remained unchanged.

PMID- 22955340
TI  - Associations of circulating 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and
      vitamin D pathway genes with prostate-specific antigen progression in men with
      localized prostate cancer undergoing active monitoring.
AB  - Current diagnostic tests cannot differentiate the majority of prostate cancers
      with a low likelihood of progression from the minority with more aggressive
      potential. We examined whether the measures of vitamin D were associated with
      prostate-specific antigen (PSA) doubling time in men undergoing active
      monitoring. We examined the associations of circulating 25-hydroxyvitamin D
      (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D pathway
      polymorphisms with PSA doubling time in 490 men undergoing active monitoring for
      localized prostate cancer within a UK population-based cohort study [mean follow
      up 4.4 years (range: 0.3-7.6)]. Repeat PSA measurements were analyzed using
      multilevel models. There was no evidence that circulating 25(OH)D levels,
      1,25(OH)2D levels, or vitamin D pathway polymorphisms were associated with
      postdiagnosis PSA doubling time. Stratifying the results by prostate cancer grade
      at diagnosis (high grade or low grade) did not alter the results. We found no
      evidence that either circulating 25(OH)D, 1,25(OH)2D, or vitamin D pathway
      polymorphisms were associated with PSA doubling time in men undergoing active
      monitoring for localized prostate cancer. Future studies should examine the
      associations of variation in vitamin D with clinical outcomes (metastases and
      death).

PMID- 22955341
TI  - Chronic eyelid swelling as an initial manifestation of myeloma-associated
      amyloidosis.
AB  - Orbital amyloidosis is uncommon and difficult to diagnose due to their variable
      clinical presentations. The authors report a case of a patient who presents with
      chronic eyelid swelling as an initial manifestation of myeloma-associated
      amyloidosis. This patient was also found to have retrobulbar infiltration with no
      visual impairment. The authors also describe the first documentation of the
      atypical necrotic appearance of amyloidosis in the involved eyelid tissues.
      Myeloma-associated amyloidosis can present as chronic, nonspecific periorbital
      swelling, hence a biopsy of the affected tissues is important in preventing a
      delay in the correct diagnosis.

PMID- 22955342
TI  - Mucus extravasation into the orbit during frontal sinus irrigation.
AB  - During minitrephination and irrigation of the frontal sinus, mucus extravasated
      into the orbit through a defect in the sinus floor. The mucus incited a foreign
      body reaction and became encapsulated within the orbit necessitating excision via
      an anterior orbitotomy.

PMID- 22955343
TI  - Use of antimetabolites in the reconstruction of severe anophthalmic socket
      contraction.
AB  - PURPOSE: The use of antimetabolites is well established in ophthalmology with
      expanded uses still being defined. We describe our experience of antimetabolite
      use in the reconstruction of severe anophthalmic socket contraction. METHODS:
      Nonrandomized, retrospective case series. The medical records and clinical
      photographs of 5 patients with severe socket contraction were reviewed. Either 5
      Fluorouracil (5-FU) (50 mg/ml) or Mitomycin C (MMC) (0.4 mg/ml) was used during
      the course of the surgery via direct injection into the operative bed in the area
      of scarring. In addition, in 3 cases, 5-FU was also applied after surgery, in the
      clinic setting. Variables examined included: number of previous socket
      operations; preoperative ability to retain a prosthesis; type of socket
      reconstruction; type, amount, and location of antimetabolite injected; number of
      postoperative injections; average follow-up; and the postoperative ability to
      retain a prosthesis. RESULTS: All 5 patients had multiple operations previously.
      After surgery, all 5 were able to retain an ocular prosthesis. We did not observe
      any delay in wound healing, implant exposure, or extrusion, and no significant
      side effects were noted. CONCLUSION: The use of adjunct antimetabolite in severe
      anophthalmic socket reconstruction is an effective option that is well tolerated
      with minimal side effects.

PMID- 22955344
TI  - The 18-gauge needle:  an innovative simple tool for frontalis sling surgery.
AB  - PURPOSE: The aim of this study was to introduce the use of the 18-gauge
      hypodermic needle as a simple and cost-effective alternative tool in frontalis
      silicone suspension ptosis surgery. METHODS: A retrospective, interventional,
      noncomparative case study was performed by reviewing 64 patients (82 eyes) who
      underwent this technique between February 2010 and January 2011. Patients with
      simple, severe congenital ptosis with poor levator excursion were included in the
      study. Patients with prior sling and levator resection surgery were excluded. All
      patients underwent unilateral or bilateral frontalis sling surgery with a
      silicone rod placed via a closed-incision pentagonal configuration. All surgeries
      were performed by a single surgeon at a tertiary referral institute using the 1.5
      inch hypodermic 18-gauge needle as an insertion guide for the silicone rod.
      Intraoperative technique, ease of surgical maneuverability, operative time, and
      postoperative results and complications were noted. RESULTS: The mean patient age
      was 10.3 years (range: 1-28 years). Fifty-six of 64 patients (87.5%) were between
      the ages of 1 and 18 years (mean: 8.5 years), and 8 of 64 (12.5%) between 9 and
      28 years (mean: 23 years). Forty-two of 64 (65.7 %) patients were female and 22
      of 64 (34.4%) were male. Forty-six of 64 (71.9%) patients underwent unilateral
      frontalis sling surgery and 18 of 64 (28.1%) patients underwent bilateral
      surgery. Follow up ranged from 12 to 18 months. In 2 of the 82 eyes (2.4%), the
      sharp end of the needle cut the silicone rod while introducing the needle from
      the medial suprabrow stab incision to the eyelid margin end in a closed
      technique, requiring replacement of the silicone rod. Average surgical time was
      15 minutes for unilateral cases and 30 minutes for bilateral cases. The main
      advantages noted intraoperatively were the small incisions that allowed for less
      operative time and minimal bleeding, easy maneuverability and control of the
      needle during tissue passage, and smooth threading of the silicone rod. Blunting
      of the tip is also eliminated as the needles are disposable. CONCLUSIONS: The 18
      gauge hypodermic needle is a simple and cost-effective alternative to other
      needles used in frontalis silicone sling ptosis surgery. Its low cost and easy
      accessibility make it a particularly quick and useful option in community-based
      practices, tertiary referral centers, and large medical eye camps globally.

PMID- 22955345
TI  - Self-disclosing my ostomy to the dominant culture: an autoethnography.
AB  - Living with an ostomy is a major change to a person's body and poses difficult
      questions about how to disclose personal medical information to others. This
      autoethnography examines my time with an ostomy through the lens of co-cultural
      theory and sheds light on how people with ostomies communicate with the dominant
      culture, in this case people without ostomies. I discuss how my communication
      goals and approaches evolved over time.

PMID- 22955346
TI  - Is L-arabinose important for the endophytic lifestyle of Pseudomonas spp.?
AB  - Twenty endophytic bacteria were isolated from surface-sterilized stems and roots
      of cucumber plants. After removal of potential siblings and human pathogens, the
      remaining seven strains were identified based on their 16S rDNA as Pseudomonas
      fluorescens (2 strains) and P. putida (5 strains). Three strains, namely P.
      fluorescens CS1, P. fluorescens CR2 and P. putida CR3, were able to suppress
      tomato foot and root rot (TFRR). Special attention was paid to the
      characterization of the BIOLOG carbon oxidation profiles of the isolated
      pseudomonads in order to identify nutrients which might be important for their
      endophytic lifestyle. Comparative analysis of the profiles of these seven strains
      with those of seven rhizospheric Pseudomonas spp. revealed that endophytes were
      able to oxidize L-arabinose and 2,3-butanediol significantly more often than the
      rhizospheric group. An independent growth experiment performed in tubes using L
      arabinose and 2,3-butanediol as sole carbon sources showed the same results as
      seen using BIOLOG for L-arabinose, but not for 2,3-butanediol. Since L-arabinose
      is one of the most abundant sugars in xylem of cucumber plants and was not
      detected in their rhizosphere, our data suggest that utilization of L-arabinose
      might be a trait contributing to the endophytic lifestyle of the isolated
      Pseudomonas endophytes.

PMID- 22955347
TI  - Yield of exciton dissociation in a donor-acceptor photovoltaic junction.
AB  - A simple model is constructed to describe dissociation of charge transfer
      excitons in bulk heterojunction solar cells, and its dependence on the physical
      parameters of the system. In bulk heterojunction organic photovoltaics (OPVs),
      exciton dissociation occurs almost exclusively at the interface between the donor
      and acceptor, following one-electron initial excitation from the HOMO to the LUMO
      levels of the donor, and charge transfer to the acceptor to make a charge
      transfer exciton. After exciton breakup, and neglecting the trapping of
      individual carriers, the electron may undergo two processes for decay: one
      process involves the electron and/or hole leaving the interface, and migrating to
      the electrode. This is treated here as the electron moving on a set of acceptor
      sites. The second loss process is radiationless decay following recombination of
      the acceptor electron with the donor cation; this is treated by adding a
      relaxation term. These two processes compete with one another. We model both the
      exciton breakup and the subsequent electron motion. Results depend on tunneling
      amplitude, energetics, disorder, Coulomb barriers, and energy level matchups,
      particularly the so-called LUMO-LUMO offset.

PMID- 22955349
TI  - FAO/WHO guidelines on probiotics: 10 years later.

PMID- 22955350
TI  - The gut barrier: new acquisitions and therapeutic approaches.
AB  - The intestinal barrier serves 2 critical functions for the survival of the
      individual: first, it allows nutrient absorption and second, it defends the body
      from dangerous macromolecule penetration. It is a complex multilayer system,
      consisting of an external "anatomic" barrier and an inner "functional"
      immunological barrier. The interaction of these 2 barriers enables equilibrated
      permeability to be maintained. Many factors can alter this balance: gut
      microflora modifications, mucus layer alterations, and epithelial damage can
      increase intestinal permeability, allowing the translocation of luminal content
      to the inner layer of intestinal wall. Several techniques are now available that
      enable us to study gut permeability: "in vitro" models (Caco-2 and HT29-MTX
      cells) and "in vivo" not invasive tests (sugar tests and radioisotope scanning
      tests) are used to estimate permeability and to suggest molecular
      pathophysiological mechanisms of intestinal permeability in health and diseases.
      Many medicinal products used in the treatment of gastrointestinal diseases have
      also found to play an active role in modulate intestinal permeability:
      corticosteroids, 5-aminosalicylic acid, anti-tumor necrosis factor, probiotics,
      and mucosal protectors, like gelatin tannate. This review will particularly
      address the role of the gut barrier in maintaining intestinal permeability
      (microbiota, mucus, and epithelial cells), the techniques used for estimating
      intestinal permeability and the therapeutic approaches able to modify it.

PMID- 22955351
TI  - The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus
      LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp.
      delbrueckii LDD01 to restore the "gastric barrier effect" in patients chronically
      treated with PPI: a pilot study.
AB  - BACKGROUND: Gastroesophageal reflux disease is a very widespread condition. In
      Europe, it is estimated that about 175 million people suffer from this disease
      and have to chronically take drugs to increase gastric pH. The proton pump
      inhibitors (PPIs) such as omeprazole, lansoprazole, and esomeprazole are the most
      widely used drug typology in this regard. However, the inhibition of normal
      gastric acid secretion has important side effects, the most important being
      bacterial overgrowth in the stomach and duodenum with a concentration of >105
      viable cells/mL. As a major consequence of this, many harmful or even pathogenic
      bacteria contained in some foods could survive the gastric transit and colonize
      either the stomach itself, the duodenum, or the gut, where they could establish
      acute and even chronic infections with unavoidable consequences for the host's
      health. In other words, the "gastric barrier effect" is strongly reduced or even
      disrupted. To date, there are no real strategies to deal with this widespread,
      although still relatively little known, problem. The aim of this study was to
      confirm the gastric bacterial overgrowth in long-term PPI consumers and to assess
      the efficacy of some probiotic bacteria, belonging to both genera Lactobacillus
      and Bifidobacterium, in the reduction of gastric and duodenal bacterial
      overgrowth, therefore partially restoring the gastric barrier effect against
      foodborne pathogenic bacteria. METHODS: For this purpose, probiotics with a
      strong demonstrated inhibitory activity on gram-negative bacteria, such as
      Escherichia coli, were tested in a human intervention trial involving a total of
      30 subjects treated with PPIs for either 3 to 12 consecutive months (short-term)
      or >12 consecutive months (long-term). An additional 10 subjects not taking PPIs
      were enrolled and used as a control group representing the general population.
      Four selected probiotics Probiotical SpA (Novara, Italy), namely Lactobacillus
      rhamnosus LR06 (DSM 21981), Lactobacillus pentosus LPS01 (DSM 21980),
      Lactobacillus plantarum LP01 (LMG P-21021), and Lactobacillus delbrueckii subsp.
      delbrueckii LDD01 (DSM 22106) were administered for 10 days to 10 subjects
      treated with PPIs for >12 months (group B). In the 60 mg formulation, N
      acetylcysteine was included as well in light of its well-known mechanical effects
      on bacterial biofilms. Gastroscopies were performed at the beginning of the study
      (d0) in all the groups (A, B, C, and D) and after 10 days (d10) in group B only;
      that is, at the end of probiotics intake. The total viable cells and total
      Lactobacillus were quantified in gastric juice and duodenal brushing material
      from all subjects. The results were compared among all the groups and with the
      control subjects (group D) to confirm the bacterial overgrowth. A comparison was
      made also between d0 and d10 in group B to quantify the efficacy of the 4
      probiotics administered for 10 days. Fecal samples were collected from all groups
      at d0, including subjects not treated with PPIs, and in group B only at d10.
      Specific bacterial classes, namely enterococci, total coliforms, E. coli, molds,
      and yeasts were quantified in all fecal specimens. RESULTS: The results collected
      confirmed the strong bacterial overgrowth in the stomach and duodenum of people
      treated with PPIs compared with subjects with a normal intragastric acidity. It
      is also worth noting that the bacterial cell counts in subjects who underwent a
      long-term treatment with a PPI were greater than the results from subjects taking
      these drugs for 3 to 12 months. The intake of 4 specific probiotic strains with a
      marked antagonistic activity towards 5 E. coli bacteria, including the
      enterohaemorrhagic O157:H7 strain, and an effective amount of N-acetylcysteine
      (NAC) was able to significantly reduce bacterial overgrowth in long-term PPI
      treated subjects. Total lactobacilli represented the major percentage of
      bacterial counts, thus demonstrating the ability of such bacteria to colonize the
      stomach and the duodenum, at least temporarily, and to consequently restore the
      gastric barrier effect. A significant decrease in fecal enterococci, total
      coliforms, E. coli, molds, and yeasts in subjects treated with PPIs was recorded
      at the end of probiotics supplementation (d10) compared with baseline (d0) in
      group B. This is a further confirmation of the barrier effect also exerted at the
      stomach level. CONCLUSIONS: PPIs are the most widely sold and used drugs in the
      world. However, the chronic use of these pharmacological molecules exposes the
      subject to the risk of foodborne infections as most pathogens are able to survive
      the gastric transit in a condition of significantly decreased acidity.

PMID- 22955352
TI  - Microbes on-air: gut and tissue microbiota as targets in type 2 diabetes.
AB  - Each individual can be distinguished by the heterogeneity of the trillions of
      microbes inhabiting his gastrointestinal tract. This concept, together with the
      role that gut microbiota is considered to play in the induction of metabolic
      diseases, paves the way for the development of personalized medicine. By
      exploiting our unique animal model of metabolic adaptation to a high-fat diet, we
      have recently shown that differential gut microbiota lead to different metabolic
      phenotypes--metabotypes. Moreover, we have also reported that a given metabotype
      can be distinguished by different profiles of gut microbes, symptomatic of the
      complexity of the regulation of host physiology by gut microbiota. Furthermore,
      in an effort to find bacterial predictors of type 2 diabetes (T2D), we discovered
      that in a healthy population, subjects who subsequently developed T2D had
      increased blood levels of bacterial 16S rDNA well before. In addition, tissue
      (blood) microbiota, mainly characterized by Proteobacteria (up to 90%), has been
      discovered both in healthy individuals and in diabetic patients. Altogether, our
      results confirm the presence of gut microbes and propose tissue microbiota as new
      targets for the innovative treatment of T2D.

PMID- 22955353
TI  - Assessment of the in vitro inhibitory activity of specific probiotic bacteria
      against different Escherichia coli strains.
AB  - BACKGROUND: Lactobacilli and bifidobacteria are often associated with health
      promoting effects. These live microorganisms, defined as probiotics, are commonly
      consumed as part of fermented foods, such as yoghurt and fermented milks, or as
      dietary supplements. Escherichia coli is a gram-negative, rod-shaped bacterium
      commonly found in the lower intestine of warm-blooded organisms. As a part of the
      normal gut microbiota, this microorganism colonizes the gastrointestinal tract of
      animals and humans within a few hours after birth. All E. coli strains can
      produce a wide variety of biogenic amines responsible for potentially harmful
      systemic intoxications. Enterohemorrhagic E. coli serotype O157:H7 is a pathotype
      of diarrhoeagenic strains with a large virulence plasmid pO157 able to produce 1
      or more Shiga toxins. METHODS: The overall aim of this study was to determine the
      inhibitory effects of different strains of probiotics on E. coli serotypes,
      including E. coli O157:H7 (CQ9485). In particular, the antagonistic activity of 4
      Bifidobacterium strains (Probiotical SpA, Italy) and 16 lactic acid bacteria,
      more specifically 14 Lactobacillus spp. and 2 Streptococcus spp., was assessed
      against selected E. coli biotypes (ATCC 8739, ATCC 10536, ATCC 35218, and ATCC
      25922). The diarrhoeagenic serotype O157:H7 was also tested. RESULTS: The
      experimental data collected demonstrated an in vitro significant inhibitory
      effect of 6 Lactobacillus strains, namely L. rhamnosus LR04, L. rhamnosus LR06,
      L. plantarum LP01, L. plantarum LP02, L. pentosus LPS01, and L. delbrueckii
      subsp. delbrueckii LDD01, and 2 Bifidobacterium strains, B. breve BR03 and B.
      breve B632. The inhibiting extent was slightly different among these strains,
      with L. delbrueckii subsp. delbrueckii LDD01 showing the highest activity on E.
      coli O157:H7. CONCLUSIONS: Most of the probiotics studied are able to antagonize
      the growth of the 5 strains of E. coli tested, including the O157:H7 biotype,
      well known for their characteristic to produce a wide variety of biogenic amines
      considered responsible for dangerous systemic intoxications.

PMID- 22955354
TI  - Unfolded protein responses in the intestinal epithelium: sensors for the
      microbial and metabolic environment.
AB  - In inflammatory bowel disease, the intestinal microbiota is a key driver of
      inflammation. Hence, efficient sensing of luminal antigens and subsequent
      initiation of adequate immune responses is crucial for maintaining homeostasis,
      particularly in intestinal epithelial cells. Pathways such as Toll-like receptor
      mediated signaling and autophagy sense microbial products to activate
      inflammatory processes and, concomitantly, interact with cellular stress
      responses such as the unfolded protein response (UPR). Proteostasis is
      particularly sensitive toward environmental challenges and triggers, such as
      oxidative stress and metabolic alterations, and impact protein folding in
      different cellular compartments. In contrast, disturbances in energy supply
      including impaired mitochondrial function and epithelial beta-oxidation have been
      suspected to contribute toward intestinal inflammation. Interestingly, the 2 main
      organelles linking metabolic pathways, inflammatory signaling and pathogen
      sensing, endoplasmic reticulum (ER) and mitochondria (mt), can trigger distinct
      UPRs, and both ER UPR and mt UPR have been shown to be disease-relevant in
      inflammatory bowel disease. The ER is essential for the coordination of metabolic
      responses through controlling the synthetic and catabolic pathways of various
      nutrients and furthermore, ER UPR signaling directly intersects with inflammation
      associated NF-kappaB and Toll-like receptor pathways. Consistently, next to their
      function in cellular energy supply, mitochondria are increasingly recognized as
      integrators of immune responses. For instance, mitochondria participate in innate
      immunity to viral infection through the pattern recognition receptor retinoic
      acid inducible gene-I and are involved in inflammasome activation. Thus, we
      hypothesize that a concerted UPR activation might represent an innate mechanism
      to sense potentially threatening changes of the mucosal metabolic environment and
      impacts host cellular functions and immune responses.

PMID- 22955355
TI  - Probiotics reduce gut microbial translocation and improve adult atopic
      dermatitis.
AB  - BACKGROUND: It has been suggested that probiotics modulate atopic dermatitis (AD)
      progression, but no data are actually available on their mechanisms of action and
      on their ability to act as immunomodulators in this pathology. OBJECTIVE: The aim
      of this randomized double-blinded active treatment versus placebo study was to
      evaluate clinical efficacy of an intake of a combination of 2 probiotics
      (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) for the treatment
      of adult AD patients. METHODS: Forty-eight patients were enrolled in the study
      (randomization ratio 2:1) and treated with a combination (LS01 and BR03) or
      placebo (maltodextrin) for 12 weeks. Clinical efficacy was assessed from baseline
      by changes in the SCORAD index and DLQ index improvement. Analysis on the gut
      permeability barrier, immunologic parameters, and changes in fecal microbiota and
      recovery of probiotics were performed at baseline, at the end of therapy, and 2
      months later. RESULTS: Patients receiving probiotics showed a significant
      improvement in clinical parameters (SCORAD, P<0.0001 and DLQ index, P=0.021) from
      baseline. The probiotics reduced microbial translocation (P=0.050), immune
      activation (P<0.001), improved T-helper cell (Th)17/regulatory T cell (Treg)
      (P=0.029) and Th1/Th2 (P=0.028) ratios. None of these changes were observed in
      the placebo group. CONCLUSIONS: Our results suggest that this specific mixture of
      probiotics (LS01 and BR03 strains) may induce beneficial effects for clinical and
      immunologic alterations in adult AD. This combination could be considered as
      adjuvant therapy for the treatment of AD in adult patients.

PMID- 22955356
TI  - Selenium and zinc internalized by Lactobacillus buchneri Lb26 (DSM 16341) and
      Bifidobacterium lactis Bb1 (DSM 17850): improved bioavailability using a new
      biological approach.
AB  - BACKGROUND: Minerals, often referred to as micronutrients, are one of the 5
      fundamental groups of nutrients needed to sustain life. Micronutrient
      malnutrition affects >50% of the worldwide population. In particular, zinc (Zn)
      deficiency is considered an emerging public health problem in India and in other
      developing countries. Selenium (Se) is another trace mineral essential for humans
      and animals. Dietary Se exists primarily as selenomethionine and selenocysteine.
      In addition, Se may be present in its inorganic form (selenite) in some
      vegetables. To increase the daily intake of these minerals, numerous food
      supplements containing different inorganic and organic forms of Zn or Se are
      commercially available. At any rate, it is quite well known that inorganic salts
      have a very low bioavailability. Organic salts, commonly based on gluconate,
      orotate, citrate, or other molecules, are characterized by a higher systemic
      effect. The innovative opportunity of using certain species of probiotics
      enriched with the 2 minerals could represent an interesting alternative to these
      preparations. Diet integration with bacteria able to internalize Zn and Se may
      embody a new application of probiotics. METHODS: To overcome the difficulties of
      in vivo animal or human trials, in this work a cell culture model using Caco-2
      cells in bicameral chambers (Transwell system) was developed and validated to
      quantify the bioavailability of some commercial forms of Se and Zn compared with
      the organic forms accumulated intracellularly by Lactobacillus buchneri Lb26 (DSM
      16341) and Bifidobacterium lactis Bb1 (DSM 17850), respectively. RESULTS: The
      experimental data collected demonstrated a significantly higher bioavailability
      of Se and Zn internalized by L. buchneri Lb26 (DSM 16341) and B. lactis Bb1 (DSM
      17850), respectively, compared with the inorganic and even organic forms tested.
      In particular, the Se accumulated at the intracellular level by L. buchneri Lb26
      proved to be 5.9, 9.4, and 65 times more absorbable than sodium selenite, seleno
      L-methionine, and seleno-L-cysteine, respectively. In contrast, Zn internalized
      by B. lactis Bb1 showed an absorption that was >16 times higher by Caco-2 cells
      compared with zinc gluconate and a 31.5 times higher absorption compared with
      zinc sulfate. Most notably, Se and Zn internalized by the 2 probiotics studied
      are the only forms able to reach the Transwell basolateral compartment at a
      concentration higher than the concentration found in the apical compartment,
      therefore suggesting a considerably higher in vivo ability to be absorbed into
      the bloodstream. Both organic and inorganic forms of Se and Zn were predominantly
      found in the apical compartment, thus demonstrating their poor ability to diffuse
      into the cell and become bioavailable in all subcellular areas. CONCLUSIONS: The
      opportunity of delivering minerals in a highly bioavailable form by means of a
      probiotic bacterium has not been deeply investigated to date. This is the first
      study reporting quantitative data on the bioavailability and percentage of
      absorption of minerals internalized by specific probiotics. The most noticeable
      aspect is the significantly higher absorption of both probiotic Se and Zn
      compared with their organic forms, with particular reference to seleno-L
      methionine, seleno-L-cysteine, and zinc gluconate.

PMID- 22955357
TI  - Role of the gut barrier in acute pancreatitis.
AB  - The small intestine is one of the distant organs that become damaged during
      severe acute pancreatitis, due to microcirculation disturbance associated with
      loss of fluids in the "third space," hypovolemia, splanchnic vasoconstriction,
      and finally an ischemia-reperfusion injury. In this scenario, the gut acts as the
      starter for severe systemic complications, as the failure of the intestinal
      barrier is associated with translocation of bacteria and inflammatory and toxic
      products produced in the intestinal wall, which can be responsible for sepsis and
      infection of the necrotic pancreas and for systemic inflammatory response.
      Therefore, one of the main goals of treatment in the early phases of severe acute
      pancreatitis should be to maintain the integrity of the gut barrier in the small
      intestine. These strategies include appropriate fluid resuscitation to limit the
      damage due to the relative hypovolemia and early enteral feeding. The role of
      intravenous antibiotics to prevent infection of the pancreatic necrosis is
      controversial and the role of probiotics, which seemed a promising tool in vitro
      and in early clinical trials, needs to be further investigated to better
      understand the effects of the single specific strains at various doses and timing
      before designing new clinical trials.

PMID- 22955358
TI  - Mucosal permeability and immune activation as potential therapeutic targets of
      probiotics in irritable bowel syndrome.
AB  - There is increasingly convincing evidence supporting the participation of the gut
      microenvironment in the pathophysiology of irritable bowel syndrome (IBS).
      Studies particularly suggest an interplay between luminal factors (eg, foods and
      bacteria residing in the intestine), the epithelial barrier, and the mucosal
      immune system. Decreased expression and structural rearrangement of tight
      junction proteins in the small bowel and colon leading to increased intestinal
      permeability have been observed, particularly in postinfectious IBS and in IBS
      with diarrhea. These abnormalities are thought to contribute to the outflow of
      antigens through the leaky epithelium, causing overstimulation of the mucosal
      immune system. Accordingly, subsets of patients with IBS show higher numbers and
      an increased activation of mucosal immunocytes, particularly mast cells. Immune
      factors, released by these cells, including proteases, histamine, and
      prostanoids, participate in the perpetuation of the permeability dysfunction and
      contribute to the activation of abnormal neural responses involved in abdominal
      pain perception and changes in bowel habits. All these mechanisms represent new
      targets for therapeutic approaches in IBS. Probiotics are an attractive
      therapeutic option in IBS given their recognized safety and by virtue of positive
      biological effects they can exert on the host. Of importance for the IBS
      pathophysiology is that preclinical studies have shown that selective probiotic
      strains exhibit potentially useful properties including anti-inflammatory
      effects, improvement of mucosal barrier homeostasis, beneficial effects on
      intestinal microbiota, and a reduction of visceral hypersensitivity. The effect
      of probiotics on IBS is positive in most randomized, controlled studies, although
      the gain over the placebo is small. Identifying tailored probiotic approaches for
      subgroups of IBS patients represents a challenge for the future.

PMID- 22955359
TI  - Changing of fecal flora and clinical effect of L. salivarius LS01 in adults with
      atopic dermatitis.
AB  - GOAL: To evaluate cytokine stimulation with 3 strains of Lactobacillus salivarius
      in vitro and to assess changes in intestinal microflora and clinical improvements
      in adults with atopic dermatitis (AD) induced by the strain showing the best
      immunomodulatory features. BACKGROUND: AD is a common skin disease in children
      and adults. It is characterized by chronic inflammation, eczema, and increasing
      intestinal permeability. Various studies have shown that patients with AD
      presented some modifications in the intestinal microbiota composition; as a
      result, intestinal microflora is thought to have a pivotal role in this disease.
      METHODS: Thirty-eight patients aged from 18 to 46 years with moderate/severe AD
      were recruited. Subjects were randomized in a double-blind placebo-controlled
      study to receive active treatment with L. salivarius LS01: probiotic (n=19) or
      placebo (n=19). Cytokine production was determined by means of specific
      quantitative enzyme-linked immunosorbent assays. Intestinal bacterial groups were
      quantified using conventional culture techniques, whereas L. salivarius LS01 was
      identified using polymerase chain reaction and pulse field gel electrophoresis.
      RESULTS: L. salivarius LS01 showed the best immunomodulatory features and it was
      chosen for the second phase of the study. AD subjects showed a reduction in their
      SCORAD score after probiotic treatment and a significant decrease in the
      staphylococci load compared with the placebo group. Moreover, L. salivarius LS01
      showed the ability to reduce the production of Th2 cytokines, maintaining the
      production of Th1 cytokines stable. CONCLUSIONS: Treatment with the L. salivarius
      LS01 strain seems to positively modify clinical and immunologic status and
      dermatology life quality in a group of adults affected by moderate/severe AD,
      leading to a rebalancing of altered intestinal microbiota.

PMID- 22955360
TI  - Microbiota, innate immune system, and gastrointestinal muscle: ongoing studies.
AB  - AIM: To test the activities of culture-extracted or commercially available toll
      like receptors (TLRs) ligands to establish their direct impact on target
      gastrointestinal motor cells. METHODS: Short-term and long-term effects of
      Shigella flexneri M90T and Escherichia coli K-2 strains-extracted
      lipopolysaccharides (LPS), commercially highly purified LPS (E. coli O111:B4 and
      EH100), and Pam2CSK4 and Pam3CSK4, which bind TLR2/6 and TLR1/2 heterodimers,
      respectively, have been assessed on pure primary cultures of colonic human smooth
      muscle cells (HSMC). RESULTS: Pathogenic Shigella-LPS and nonpathogenic E. coli K
      2-LPS induced a time-dependent decrease of resting cell length and acetylcholine
      induced contraction, with both alterations occurring rapidly and being more
      pronounced in response to the former. However, their effects differed, prolonging
      HSMC exposure with Shigella-LPS effects maintained throughout the 4 hours of
      observation compared with E. coli K-2-LPS, which disappeared after 60 minutes of
      incubation. Similar differences in magnitude and time dependency of myogenic
      effects were observed between pure TLR4 and TLR2/1 or TLR2/6 ligands. The
      specific activation of TLR4 with LPS from pathogen or nonpathogen E. coli,
      O111:B4 and EH100, respectively, induced smooth muscle alterations that
      progressively increased, prolonging incubation, whereas TLR2 ligands induced
      short-term alterations, of a lesser magnitude, which decreased over time. The
      real-time polymerase chain reaction analysis showed that HSMC express mRNA for
      TLR1, 2, 4, and 6, substantiating a direct effect of TLR ligands on human colonic
      smooth muscle. CONCLUSIONS: This study highlights that bacterial products can
      directly affect gastrointestinal motility and that TLRs subtypes may differ in
      their cellular activity.

PMID- 22955362
TI  - Supplementation of infant formula with probiotics/prebiotics: lessons learned
      with regard to documenting outcomes.
AB  - In 2011, the Committee on Nutrition of the European Society for Paediatric
      Gastroenterology, Hepatology, and Nutrition systematically reviewed published
      evidence on the safety and health effects of the administration of formulae
      supplemented with probiotics and/or prebiotics compared with unsupplemented
      formulae. The document could serve as an example of problems relating to the
      choice and definition of outcomes assessing the addition of new ingredients to
      infant formulae. The studies were often too small with insufficient power to
      identify relevant effects, and the follow-up periods in the trials were too
      short. The clinical outcomes, even those relating to the same domain (eg,
      gastrointestinal infections) differed. Even if the same outcomes were measured,
      the definitions of the outcomes were heterogenous, often not widely agreed upon,
      or just lacking. The use of inappropriate outcome measures and/or their
      definitions may result in misleading conclusions. It may also lead to an
      overestimation or underestimation of potential benefits of the intervention or
      fail to reveal any potential benefits. There is a need for well-designed and
      carefully conducted randomized controlled trials, with relevant
      inclusion/exclusion criteria and adequate sample sizes. These studies should use
      validated clinical outcome measures.

PMID- 22955361
TI  - Interactions between intestinal microbiota and innate immune system in pediatric
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is the result of an altered immune homeostasis
      within the intestinal mucosa against the gut microbiota, leading to chronic
      inflammation in genetically predisposed individuals. Under normal conditions, the
      immune system defends against pathogens and prevents the passage of excessive
      intestinal bacteria; regulatory pathways must maintain a low-grade, controlled
      inflammation in a healthy gut, but also induce a protective response against
      pathogens. The innate immune system is the first-line defense from microbes;
      dendritic cells, macrophages, and epithelial cells produce an initial, immediate
      response. The immune system constantly controls commensal bacteria and utilizes
      constitutive antimicrobial mechanisms to sustain immune homeostasis. The
      discovery that several genes linked to IBD modulate microbial recognition and
      innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), and
      genes that mediate autophagy (ie, ATG16L1, IRGM), has highlighted the critical
      role of host-microbe interactions in controlling intestinal immune homeostasis.
      Commensal microorganisms actively interact with the intestinal mucosa and
      influence the activity of the immune system as well as the amplitude of the
      immune response. In contrast, host factors can influence microbes, which in turn
      modulate disease susceptibility. In this paper, we focus on the mechanisms that
      mediate host-microbe interactions and how the disruption of this balance leads to
      chronic intestinal inflammation in IBD.

PMID- 22955363
TI  - Probiotics in childhood: allergic illness and respiratory infections.
AB  - Over the last decade, there has been a growing interest in the use of probiotics
      for allergic diseases. In the last years, some studies showed a significant
      improvement for atopic eczema by the administration of probiotics during
      pregnancy and postnatally. About food allergy, probiotics administration seems to
      be effective in the management of food allergy symptoms but has no effect on the
      prevention of sensitization. In the international literature, there are few
      studies that evaluated the probiotic effect on allergic rhinitis, and authors
      reported that probiotics might have a beneficial effect in AR by reducing symptom
      severity and medication use. Another major potential benefit of probiotics has
      been suggested in patients with asthma. On this topic, several studies have been
      carried out using different probiotics and the results have not been univocal.
      Indeed, probiotics seems to be able to offer protection about common cold and
      respiratory infections in healthy and hospitalized children.

PMID- 22955364
TI  - Effectiveness of the association of 2 probiotic strains formulated in a slow
      release vaginal product, in women affected by vulvovaginal candidiasis: a pilot
      study.
AB  - BACKGROUND: Vulvovaginal candidiasis (VVC) is the second most common cause of
      vaginitis after bacterial vaginosis, and it is diagnosed in up to 40% of women
      with vaginal complaints in the primary care setting. Among Candida spp., Candida
      albicans is the most common infectious agent. The treatment of choice for
      uncomplicated VVC is achieved with single-dose or short-course therapy in over
      90% of cases. Several topical and oral drugs are available, without evidence for
      superiority of any agent or route of administration. In any case, most classic
      treatments are unable to significantly offer a protection against possible
      recurrences. In recent years, probiotics are emerging as a new strategy to
      counteract VVC. In fact, they are well known for their ability to lower
      intravaginal pH, thus establishing a barrier effect against many types of yeasts.
      Some strains are also able to exert additional and more focused antagonistic
      activities mediated by specific molecules such as hydrogen peroxide and
      bacteriocins. For example, Lactobacillus fermentum LF5 (CNCM I-789) was
      successfully tested in 4 human trials involving a total of 340 women reporting
      VVC at enrollment. In any case, the way used to deliver probiotics to the vaginal
      environment represents a crucial point. The aim of this work was to first select
      1 or more probiotic strains in vitro with an antagonistic activity on Candida
      yeasts and then to perform an in vivo human pilot study using an association of
      the most promising and active bacteria. METHODS: For this purpose, 2 probiotic
      strains Probiotical S.p.A (Italy) were selected based on their strong in vitro
      inhibition activity toward 4 particular Candida species, namely C. albicans,
      Candida glabrata, Candida parapsilosis, and Candida krusei and subsequently
      tested in a human intervention pilot trial involving 30 women with VVC. The
      probiotics used, L. fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02
      (DSM 21717), were administered by means of slow release effervescent vaginal
      tablets (ActiCand 30 product). The main endpoint was the assessment of the
      establishment and maintenance of a barrier effect against Candida yeasts in women
      suffering from VVC. Thirty female subjects who were diagnosed with VVC by both
      microscopic examination and yeast culture were enrolled in the study and directed
      to apply a vaginal tablet once a day for 7 consecutive nights, followed by 1
      tablet every 3 nights for a further 3-week application (acute phase) and,
      finally, 1 tablet per week to maintain a long-term vaginal colonization against
      possible recurrences. A medical examination of each patient was performed at
      enrollment (d0), at the end of the first 4 weeks of treatment (d28), and at the
      end of the second month of relapse prevention (d56). The visual and microscopic
      examination was always accompanied by microbiological analyses of vaginal swabs
      to assess the presence of Candida. A statistical comparison was made between d28,
      or d56, and d0, and between d56 and d28 to quantify the efficacy against possible
      recurrences. RESULTS: The administration of the product ActiCand 30 was able to
      significantly solve Candida yeast symptoms after 28 days in 26 patients out of 30
      (corresponding to 86.6%, P<0.001). At the end of the second month, recurrences
      were recorded, albeit not particularly serious, in only 3 out of 26 patients
      (11.5%, P=0.083) who were found to have fully healed at the end of the first
      month of treatment. This is a further confirmation of the long-term barrier
      effect exerted by the product. CONCLUSIONS: VVC has a very high incidence as 70%
      to 75% of women report at least 1 episode during the life. Many treatments are
      currently available but, despite a relatively high effectiveness in the relief of
      symptoms typically associated with acute infections, they are generally unable to
      offer a long-term protective barrier against possible recurrences. This study
      demonstrated the ability of ActiCand 30 to not only solve Candida infections in a
      very high percentage of women, but also to exert a long-term physiological
      defense due to the colonization of vaginal microbiota and adhesion of the mucosa
      to the epithelial cells. The special formulation of ActiCand 30, consisting of
      slow release effervescent vaginal tablets, is able to mediate 2 types of barrier
      effects, the first represented by the formation of an anaerobic environment due
      to the release of CO2 and the second guaranteed by the colonization and adhesion
      to the vaginal epithelium of the 2 probiotics L. fermentum LF10 and L.
      acidophilus LA02.

PMID- 22955365
TI  - Cultivable and pyrosequenced fecal microflora in centenarians and young subjects.
AB  - GOAL: The aim of this study was to characterize the composition of the intestinal
      microbiota in healthy centenarians in comparison with younger adults, considering
      both quantitative and qualitative aspects of gut community structure. BACKGROUND:
      The gut microbiota plays an essential role in human health. Toward seniority, its
      balance is affected by deep physiological changes. Long-lived people (age >90 y)
      have unusual features that differ from the younger elderly, so they should be
      considered separately when analyzing age-related features. However, they have
      been included in few studies and they have usually been grouped together with the
      younger elderly. STUDY: The gut microbiota of 14 centenarians and 10 younger
      adults was analyzed. Cultivable bacteria belonging to the following groups were
      enumerated: enterobacteriaceae, Enterococcus, Staphylococcus, Lactobacillus,
      Bifidobacterium, Clostridium, Bacteroides, and yeast. Lactobacilli and
      Bifidobacteria were further characterized at the species level by pyrosequencing.
      RESULTS: : In centenarians, we observed a reduction in the quantity of
      enterobacteriaceae, bifidobacteria, and bacteroides and an increase in clostridia
      sensu stricto (P<0.05). The number of Lactobacillus and Bifidobacterium species
      isolated in centenarians and younger adults was similar. The composition of the
      Lactobacillus subpopulation was quite different between the groups. The presence
      of Bifidobacterium longum in the gut seems to be a particular feature in
      centenarians. It is interesting to note that only 1 strain of B. longum was
      isolated from each centenarian subject. CONCLUSIONS: The gut microbiota of
      centenarians has particular features that differ from both younger adults and the
      younger elderly. Further studies would help to understand whether the intestinal
      microbiota can influence life expectancy and whether the administration of
      probiotic bacteria could help to extend the longevity of human life.

PMID- 22955366
TI  - Comparison of the kinetics of intestinal colonization by associating 5 probiotic
      bacteria assumed either in a microencapsulated or in a traditional, uncoated
      form.
AB  - BACKGROUND: Beneficial findings concerning probiotics are increasing day by day.
      However, one of the most important parameters able to significantly affect the
      probiotic value of a microorganism is its survival during the transit through the
      stomach and the duodenum. Some techniques may be applied that aim to improve this
      parameter, but microencapsulation of bacterial cells remains one of the most
      important. A recent study assessed the kinetics of intestinal colonization by a
      mixture of 2 probiotic strains, given either in a microencapsulated or in a
      traditional, uncoated form. METHODS: A comparison between the intestinal
      colonization by associating 5 microencapsulated bacteria and the same uncoated
      strains was performed by a double-blind, randomized, cross-over study. The study
      (December 2007 to January 2009) involved 53 healthy volunteers. In particular,
      subjects were divided into 2 groups: group A (27 subjects) was given a mix of
      probiotic strains Probiotical S.p.A. (Novara, Italy), Lactobacillus acidophilus
      LA02 (DSM 21717), Lactobacillus rhamnosus LR04 (DSM 16605), L. rhamnosus GG, or
      LGG (ATCC 53103), L. rhamnosus LR06 (DSM 21981), and Bifidobacterium lactis BS01
      (LMG P-21384) in an uncoated form, whereas group B (26 subjects) received the
      same strains microencapsulated with a gastroprotected material. The uncoated
      strains were administered at 5*109 cfu/strain/d (a total of 25*109 cfu/d) for 21
      days, whereas the microencapsulated bacteria were given at 1*109 cfu/strain/d (a
      total of 5*109 cfu/d) for 21 days. At the end of the first period of
      supplementation with probiotics, a 3-week wash-out phase was included in the
      study setting. At the end of the wash-out period, the groups crossed over their
      treatment regimen; that is, group A was administered the microencapsulated
      bacteria and group B the uncoated bacteria. The administered quantities of each
      strain were the same as the first treatment. A quantitative evaluation of
      intestinal colonization by probiotics, either microencapsulated or uncoated, was
      undertaken by examining fecal samples at the beginning of the study (time 0),
      after 10 days and after 21 days of each treatment period. In particular, fecal
      total Lactobacilli, heterofermentative Lactobacilli, and total Bifidobacteria
      were quantified at each checkpoint. A genomic analysis of an appropriate number
      of colonies was performed to quantify individual L. rhamnosus strains among
      heterofermentative Lactobacilli. RESULTS: A statistically significant increase in
      the fecal amounts of total Lactobacilli, heterofermentative Lactobacilli, and
      total Bifidobacteria was registered in both groups at the end of each
      supplementation period compared with d0 or d42 (group A: P=0.0002, P=0.0001, and
      P<0.0001 at d21, P=0.0060, P=0.0069, and P<0.0001 at d63 for total Lactobacilli,
      heterofermentative Lactobacilli, and Bifidobacteria, respectively; group B:
      P=0.0002, P=0.0006, and P<0.0001 at d21, P=0.0015, P=0.0016, and P<0.0001 at d63
      for total Lactobacilli, heterofermentative Lactobacilli, and Bifidobacteria,
      respectively), confirming the ability of each strain in the administered
      composition to colonize the human gut, whether supplemented in a gastroprotected
      or in a traditional freeze-dried form. On the contrary, subjects receiving
      microencapsulated bacteria reported a kinetics of intestinal colonization that
      was entirely comparable with those who were given uncoated strains at a 5 times
      higher amount. CONCLUSIONS: The microencapsulation technique used in this study
      is a valid approach aimed to significantly improve the survival of strains during
      gastroduodenal transit, thus enhancing their probiotic value and allowing the use
      of a 5 times lower amount.

PMID- 22955367
TI  - The European role on traditional herbal medicinal products and traditional plant
      food supplements.
AB  - Herbs are used in Europe as medicinal products, food, food supplements, and
      related products. This paper will discuss the concepts of Traditional Herbal
      Medicines and Traditional Plant Food Supplements, defined in European legislation
      under differing legal frameworks, regarding Traditional Plant Food Supplements
      (including Claims Regulation) and the role of the European Food Safety Authority
      in health claims.

PMID- 22955368
TI  - Colonic metabolism of polyphenols from coffee, green tea, and hazelnut skins.
AB  - Dietary polyphenolic compounds are poorly absorbed in the small intestine. The
      absorbed fraction follows the common metabolic pathway of drugs, undergoing phase
      II enzymatic detoxification with the conjugation of glucuronic acid, sulfate, and
      methyl groups. However, the unabsorbed fraction can reach the colon, becoming
      available for the wide array of enzymes produced by the local commensal
      microbiota. Gut bacteria can hydrolyze glycosides, glucuronides, sulfates,
      amides, esters, and lactones and are able to break down the polyphenolic skeleton
      and perform reactions of reduction, decarboxylation, demethylation, and
      dehydroxylation. These complex modifications generate several low-molecular
      weight metabolites that can be efficiently absorbed in situ, subsequently
      undergoing further phase II metabolism, locally and/or at the liver level, before
      entering the systemic blood circulation and finally being excreted in urine in
      substantial quantities that exceed the excretion of phenolic metabolites formed
      in the upper gastrointestinal tract. This brief work focuses on the phenolic
      composition and colonic microbial transformation of 2 of the most polyphenol-rich
      dietary sources, namely, green tea and coffee, and a new interesting and
      innovative ingredient, hazelnut skin, recently evaluated as one of the richest
      edible sources of polyphenolic compounds.

PMID- 22955370
TI  - Cold resistance depends on acclimation and behavioral caste in a temperate ant.
AB  - Adjusting to low temperatures is important for animals living in cold
      environments. We studied the chill-coma recovery time in temperate ant workers
      (Temnothorax nylanderi) from colonies collected in autumn and spring in Germany.
      We experimentally acclimated these ant colonies to cold temperatures followed by
      warm temperatures. As expected, cold-acclimated workers recovered faster from
      freezing temperatures, but subsequent heat acclimation did not change the short
      recovery times observed after cold acclimation. Hence, either heat acclimation
      improves cold tolerance, possibly as a general response to stress, or at least it
      does not negate enhanced cold tolerance following cold acclimation. Colonies
      collected in spring showed similar cold tolerance levels to cold-acclimated
      colonies in the laboratory. Next, we compared the chill-coma recovery time of
      different worker castes and found that exterior workers recovered faster than
      interior workers. This difference may be related to their more frequent exposure
      to cold, higher activity level, or distinct physiology. Interior workers were
      also heavier and showed a higher gaster-to-head ratio and thorax ratio compared
      to exterior workers. An obvious difference between exterior and interior workers
      is activity level, but we found no link between activity and cold tolerance. This
      suggests that physiology rather than behavioral differences could cause the
      increased cold tolerance of exterior workers. Our study reveals the importance of
      acclimation for cold tolerance under natural and standardized conditions and
      demonstrates differences in cold tolerance and body dimensions in monomorphic
      behavioral castes of an ant.

PMID- 22955371
TI  - Decaleside: a new class of natural insecticide targeting tarsal gustatory sites.
AB  - Natural sources for novel insecticide molecules hold promise in view of their eco
      friendly nature, selectivity, and mammalian safety. Recent progress in
      understanding the biology of insect olfaction and taste offers new strategies for
      developing selective pest control agents. We have isolated two natural
      insecticidal molecules from edible roots of Decalepis hamiltonii named
      Decalesides I and II, which are novel trisaccharides, highly toxic to household
      insect pests and stored-product insects. We have experimentally shown that
      insecticidal activity requires contact with tarsi on the legs but is not toxic
      orally. The insecticidal activity of molecules is lost by hydrolysis, and various
      sugars modify toxic response, showing that the insecticidal activity is via
      gustatory sites on the tarsi. Selective toxicity to insects by virtue of their
      gustatory site of action and the mammalian safety of the new insecticides is
      inherent in their chemical structure with 1-4 or 1-1 alpha linkage that is easily
      hydrolyzed by digestive enzymes of mammals. Decalesides represent a new chemical
      class of natural insecticides with a unique mode of action targeting tarsal
      chemosensory/gustatory system of insects.

PMID- 22955372
TI  - Migratory sialocele after fine-needle aspiration of the parotid gland: would it
      be possible?

PMID- 22955373
TI  - The selective BH4-domain biology of Bcl-2-family members: IP3Rs and beyond.
AB  - Anti-apoptotic Bcl-2-family members not only neutralize pro-apoptotic proteins
      but also directly regulate intracellular Ca(2+) signaling from the endoplasmic
      reticulum (ER), critically controlling cellular health, survival, and death
      initiation. Furthermore, distinct Bcl-2-family members may selectively regulate
      inositol 1,4,5-trisphosphate receptor (IP3R): Bcl-2 likely acts as an endogenous
      inhibitor of the IP3R, preventing pro-apoptotic Ca(2+) transients, while Bcl-XL
      likely acts as an endogenous IP3R-sensitizing protein promoting pro-survival
      Ca(2+) oscillations. Furthermore, distinct functional domains in Bcl-2 and Bcl-XL
      may underlie the divergence in IP3R regulation. The Bcl-2 homology (BH) 4 domain,
      which targets the central modulatory domain of the IP3R, is likely to be Bcl-2's
      determining factor. In contrast, the hydrophobic cleft targets the C-terminal
      Ca(2+)-channel tail and might be more crucial for Bcl-XL's function. Furthermore,
      one amino acid critically different in the sequence of Bcl-2's and Bcl-XL's BH4
      domains underpins their selective effect on Ca(2+) signaling and distinct
      biological properties of Bcl-2 versus Bcl-XL. This difference is evolutionary
      conserved across five classes of vertebrates and may represent a fundamental
      divergence in their biological function. Moreover, these insights open novel
      avenues to selectively suppress malignant Bcl-2 function in cancer cells by
      targeting its BH4 domain, while maintaining essential Bcl-XL functions in normal
      cells. Thus, IP3R-derived molecules that mimic the BH4 domain's binding site on
      the IP3R may function synergistically with BH3-mimetic molecules selectivity
      suppressing Bcl-2's proto-oncogenic activity. Finally, a more general role for
      the BH4 domain on IP3Rs, rather than solely anti-apoptotic, may not be excluded
      as part of a complex network of molecular interactions.

PMID- 22955374
TI  - Decoding the non-coding RNAs in Alzheimer's disease.
AB  - Non-coding RNAs (ncRNAs) are integral components of biological networks with
      fundamental roles in regulating gene expression. They can integrate sequence
      information from the DNA code, epigenetic regulation and functions of multimeric
      protein complexes to potentially determine the epigenetic status and
      transcriptional network in any given cell. Humans potentially contain more ncRNAs
      than any other species, especially in the brain, where they may well play a
      significant role in human development and cognitive ability. This review
      discusses their emerging role in Alzheimer's disease (AD), a human pathological
      condition characterized by the progressive impairment of cognitive functions. We
      discuss the complexity of the ncRNA world and how this is reflected in the
      regulation of the amyloid precursor protein and Tau, two proteins with central
      functions in AD. By understanding this intricate regulatory network, there is
      hope for a better understanding of disease mechanisms and ultimately developing
      diagnostic and therapeutic tools.

PMID- 22955375
TI  - Heavy and light roles: myosin in the morphogenesis of the heart.
AB  - Myosin is an essential component of cardiac muscle, from the onset of
      cardiogenesis through to the adult heart. Although traditionally known for its
      role in energy transduction and force development, recent studies suggest that
      both myosin heavy-chain and myosin light-chain proteins are required for a
      correctly formed heart. Myosins are structural proteins that are not only
      expressed from early stages of heart development, but when mutated in humans they
      may give rise to congenital heart defects. This review will discuss the roles of
      myosin, specifically with regards to the developing heart. The expression of each
      myosin protein will be described, and the effects that altering expression has on
      the heart in embryogenesis in different animal models will be discussed. The
      human molecular genetics of the myosins will also be reviewed.

PMID- 22955378
TI  - Radiologic case study. Multiple myeloma with cadaveric graft reconstruction of
      the ilium.

PMID- 22955379
TI  - Beneficial effect of omega-3 fatty acids on bone metabolism.

PMID- 22955377
TI  - What mechanisms/processes underlie radiation-induced genomic instability?
AB  - Radiation-induced genomic instability is a modification of the cell genome found
      in the progeny of irradiated somatic and germ cells but that is not confined on
      the initial radiation-induced damage and may occur de novo many generations after
      irradiation. Genomic instability in the germ line does not follow Mendelian
      segregation and may have unpredictable outcomes in every succeeding generation.
      This phenomenon, for which there is extensive experimental data and some evidence
      in human populations exposed to ionising radiation, is not taken into account in
      health risk assessments. It poses an unknown morbidity/mortality burden. Based on
      experimental data derived over the last 20 years (up to January 2012) six
      mechanistic explanations for the phenomenon have been proposed in the peer
      reviewed literature. This article compares these hypotheses with the empirical
      data to test their fitness to explain the phenomenon. As a conclusion, the most
      convincing explanation of radiation-induced genomic instability attributes it to
      an irreversible regulatory change in the dynamic interaction network of the
      cellular gene products, as a response to non-specific molecular damage, thus
      entailing the rejection of the machine metaphor for the cell in favour of one
      appropriate to a complex dissipative dynamic system, such as a whirlpool. It is
      concluded that in order to evaluate the likely morbidity/mortality associated
      with radiation-induced genomic instability, it will be necessary to study the
      damage to processes by radiation rather than damage to molecules.

PMID- 22955380
TI  - Association of low-energy femoral shaft fractures and bisphosphonate use.

PMID- 22955376
TI  - Thyroid hormone actions in liver cancer.
AB  - The thyroid hormone 3,3',5-triiodo-L-thyronine (T3) mediates several
      physiological processes, including embryonic development, cellular
      differentiation, metabolism, and the regulation of cell proliferation. Thyroid
      hormone receptors (TRs) generally act as heterodimers with the retinoid X
      receptor (RXR) to regulate target genes. In addition to their developmental and
      metabolic functions, TRs have been shown to play a tumor suppressor role,
      suggesting that their aberrant expression can lead to tumor transformation.
      Conversely, recent reports have shown an association between overexpression of
      wild-type TRs and tumor metastasis. Signaling crosstalk between T3/TR and other
      pathways or specific TR coregulators appear to affect tumor development. Since TR
      actions are complex as well as cell context-, tissue- and time-specific, aberrant
      expression of the various TR isoforms has different effects during diverse
      tumorigenesis. Therefore, elucidation of the T3/TR signaling mechanisms in
      cancers should facilitate the identification of novel therapeutic targets. This
      review provides a summary of recent studies focusing on the role of TRs in
      hepatocellular carcinomas (HCCs).

PMID- 22955381
TI  - Role of endostatin in orthopedics.

PMID- 22955383
TI  - Orthopedic trauma.

PMID- 22955384
TI  - Percutaneous inflation osteoplasty for indirect reduction of depressed tibial
      plateau fractures.
AB  - Anatomic reduction of articular depression tibial plateau fractures is
      challenging. The authors describe a new technique using percutaneous balloon
      guided inflation osteoplasty for a depressed lateral tibial plateau fracture. The
      fluoroscopy-guided inflation osteoplasty restores the joint surface anatomically
      in a minimally invasive fashion. The metaphyseal void is filled with a fast
      setting fluid-phase bone substitute, and a lateral buttress plate is applied with
      less invasive incisions. This technique is a valid alternative for indirect
      reduction of depressed articular tibial plateau fractures.

PMID- 22955385
TI  - Temporizing management of pediatric femur fractures using J-splints.
AB  - This article describes a novel splinting technique for the temporizing management
      of pediatric femur fractures. The J-splint is a reliable, simple, and rapidly
      applied splint that prevents many of the complications and pitfalls of other
      described temporizing measures, such as skeletal traction, skin traction,
      traction splinting, and posterior splinting. This technique of J-splinting femur
      fractures has low morbidity and provides many advantages in the temporizing
      management of pediatric femur fractures.

PMID- 22955386
TI  - Initial management of patients with traumatic spinal cord injuries.

PMID- 22955387
TI  - Potential of placenta-derived mesenchymal stem cells as seed cells for bone
      tissue engineering: preliminary study of osteoblastic differentiation and
      immunogenicity.
AB  - Mesenchymal stem cells (MSCs) have been isolated from a variety of human tissues
      (eg, bone marrow, peripheral blood, muscle, fat, umbilical blood, amniotic fluid,
      embryonic tissues, and placenta). Placenta-derived MSCs (PDMSCs) have received
      considerable interest because of their wide availability and absence of ethical
      concerns. The authors characterized the biological properties, ultrastructure,
      growth factor production, and osteoblastic differentiation of PDMSCs and
      investigated their potential as seed cells for bone tissue engineering.

PMID- 22955388
TI  - Upper-extremity stress fractures: distribution and causative activities in 70
      patients.
AB  - Stress fractures of the upper extremity and thorax are often unrecognized
      injuries in athletes and nonathletes. The authors reviewed the causative
      activities and anatomic distribution of rib and upper-extremity stress fractures.
      Radiographic and clinical information was reviewed for each case to determine
      anatomic site and causative activity of each stress fracture. Stress fracture,
      although an uncommon diagnosis outside the lower extremity and lumbar spine,
      should be included in the differential diagnosis of patients with pain in the
      ribs and upper extremity.

PMID- 22955390
TI  - Operative versus nonoperative treatment of unstable lateral malleolar fractures:
      a randomized multicenter trial.

PMID- 22955391
TI  - Groin pain in a young man.

PMID- 22955392
TI  - Understanding the burden of osteoporosis and use of the World Health Organization
      FRAX.
AB  - Fracture prevention is a critical component of managing osteoporosis, which is
      not longer defined by T-score alone. The internationally validated World Health
      Organization Fracture Risk Assessment Tool (FRAX) provides the clinician a state
      of-the-art tool for predicting patients at greatest risk for fracture. The FRAX
      tool takes into account country, bone mineral density of the hip (when
      available), age, sex, and 8 clinical risk factors to calculate the 10-year
      probability of a major osteoporotic fracture and the 10-year probability of a hip
      fracture. From this tool, an absolute fracture risk is generated, aiding
      clinicians in determining which patients with low bone mass and osteoporosis to
      treat.

PMID- 22955393
TI  - Association between low admission Norton scale scores and postoperative
      complications after elective THA in elderly patients.
AB  - The Norton scoring system is used by nurses to evaluate pressure ulcer risk. The
      authors have previously shown that low admission Norton scale scores (ANSS) are
      associated with postoperative complications other than pressure ulcers following
      hip fracture and spine fracture surgery in elderly patients. The purpose of this
      retrospective, cross-sectional study study was to determine whether low ANSS are
      associated with postoperative complications other than pressure ulcers following
      elective total hip arthroplasty (THA) in elderly patients. The medical charts of
      consecutive elderly (older than 65 years) patients admitted between February 2008
      and November 2010 were studied for acute renal failure, cardiovascular events,
      confusion, pneumonia, pressure ulcers, urinary infection, urinary retention,
      venous thromboembolism, wound infection, and other complications. The final
      cohort included 166 patients (108 [65.1%] women; aged 75.2+/-6.4 years). Overall,
      24 (14.5%) patients had low (16 or less) ANSS. Patients with low ANSS had
      significantly more postoperative complications other than pressure ulcers
      compared with patients with high ANSS (0.5+/-0.7 vs 0.2+/-0.4, respectively;
      P=.018). Binary regression analysis showed that low ANSS were independently
      associated with all postoperative complications other than pressure ulcers
      (P=.039). In addition to predicting pressure ulcer risk, the Norton scoring
      system may be used for predicting other postoperative complications in elderly
      patients following elective THA.

PMID- 22955394
TI  - Large-diameter Delta ceramic-on-ceramic versus common-sized ceramic-on
      polyethylene bearings in THA.
AB  - The higher failure rate of total hip arthroplasty (THA) in young, active patients
      remains a challenge for surgeons. Recently, larger-diameter femoral heads
      combined with an alumina matrix composite ceramic (BIOLOX Delta; CeramTec AG,
      Plochingen, Germany) articulation was developed to improve implant longevity and
      meet patients' activity demands while reducing the risk of component-related
      complications. The purpose of this study was to determine whether this new device
      may provide advantages for young, active patients. A prospective, randomized,
      controlled trial was conducted on 93 patients (113 THAs) with more than 3 years
      of follow-up. Patients were randomly divided into a study group (51 THAs) with a
      36-mm Delta ceramic-on-ceramic (COC) articulation and a control group (62 THAs)
      with a common-sized alumina ceramic head on polyethylene liner (COP)
      articulation. Clinical and radiographic results were collected to compare the
      outcomes and complications, including implant-related failures, osteolysis, and
      noises. The large-diameter Delta COC articulation provided greater range of
      motion improvement (6.1 degrees  more), similar Harris Hip Scores, and similar
      complication rates compared with the alumina COP articulation. This study
      suggests that in the short term, the large-diameter Delta COC articulation
      results in better range of motion with no higher complication rates; however, mid
      term (8-10 years) or longer follow-up is necessary to determine its superiority
      in young, active patients.

PMID- 22955395
TI  - Nontraumatic osteonecrosis of the femoral head: endoscopic visualization of its
      avascular burden.
AB  - The purpose of this study was to evaluate the intraosseous use of a flexible
      endoscope during core decompression in identifying avascular bone in the femoral
      head that did not meet magnetic resonance imaging diagnostic criteria for
      osteonecrosis. The flexible endoscope was used to visually examine and locate
      avascular bone in the entire core track. A high-speed burr was then used to
      debride the avascular bone. This debridement process was continued until a host
      bed of porous bleeding cancellous bone was observed, comprising thorough
      debridement of the femoral head. Autologous cancellous bone graft was then packed
      into the residual cavity and stabilized. Ten patients (13 hips total) with an
      average age of 49 years (range, 34-58 years) were included in the study. Eight
      patients were fully ambulatory at 3 weeks (range, 1-3 weeks). For all 13 hips,
      the mean preoperative Harris Hip Score was 43 (range, 30-75) and improved to a
      mean of 93 (range, 60-100) postoperatively. Eighty-five percent of patients (11
      of 13 hips) demonstrated a good to excellent outcome at a minimum 2-year follow
      up (range, 27-45 months). Flexible intraosseous endoscopy helped identify
      avascular bone that did not appear on the preoperative magnetic resonance
      imaging, safely widen the surgical margins of the core decompression track, and
      achieve thorough debridement of the femoral head using a minimally invasive
      technique.

PMID- 22955396
TI  - Percutaneous acetabuloplasty: a cadaveric study.
AB  - Periacetabular osteolysis is a common etiology of prosthesis failure in patients
      who undergo total hip arthroplasty. These lesions are treated by open and, more
      recently, percutaneous techniques. The purpose of this study was to determine the
      relevant surface anatomy and bony landmarks in establishing percutaneous access
      to periacetabular regions and identifying critical at-risk structures in
      establishing access. Percutaneous access to the periacetabular region was
      established superiorly, anteroinferiorly, and posteroinferiorly by using 5 L5-to
      mid thigh fixed cadaver pelvises with latex-injected vessels using threaded
      guidewires. Dissection was completed to identify structures at risk, with the
      distance from the wires recorded to the nearest millimeter. C-arm position for
      the optimal visualization and placement of guidewires was recorded. Average
      distance from the pin and the at-risk structures ranged from 11.2 to 38.7 mm. All
      3 approaches allowed for safe percutaneous access to the periacetabular regions
      without injuring significant anatomical structures. This study established safe
      starting points and orientation for guidewires and radiograph projections
      associated with percutaneous access to the periacetabular regions. The findings
      in this study will be useful for developing minimally invasive approaches to
      these regions for the treatment of osteolytic lesions of diverse etiology.
      However, a biomechanical evaluation of the impact of these bony channels on the
      strength of pelvis under physiological and unanticipated loading must be
      performed before this technique can be safely translated to clinical practice.

PMID- 22955397
TI  - Effects of a less-invasive surgical technique on cement mantle quality in total
      knee arthroplasty.
AB  - The purpose of this study was to assess the effects of a less-invasive midvastus
      exposure during total knee arthroplasty (TKA) on cement mantle grade compared
      with a standard parapatellar arthrotomy and standard TKA. Fifty consecutive
      cemented minimally invasive TKAs using a midvastus approach, patellar subluxation
      without eversion, and less-invasive instrumentation were compared
      radiographically with a control cohort of 50 consecutive cemented standard TKAs.
      To eliminate patient selection bias, the standard cohort included consecutive
      surgeries completed before 2004, prior to the advent of minimally invasive
      techniques in TKA. Analog supine anteroposterior and lateral radiographs were
      evaluated using Ewald's criteria. Lucent lines, cement voids, and cement debris
      were recorded for each group. Radiographic analysis revealed compromised femoral
      component cement mantle grades in the minimally invasive group. The number of
      anterior femoral cement voids (zone 1) was significantly higher in the minimally
      invasive group, and peripatellar and tibial cement debris was also more common in
      the minimally invasive group. Based on these findings, the midvastus approach
      compromises the surgeon's ability to duplicate a consistent femoral cement mantle
      obtained using a standard exposure.

PMID- 22955398
TI  - Robot-assisted implantation improves the precision of component position in
      minimally invasive TKA.
AB  - Minimally invasive and robot-assisted procedures have potential advantages when
      used for total knee arthroplasty (TKA). The purpose of this cadaveric study was
      to examine whether robot-assisted minimally invasive procedures improve TKA
      alignment after modifying the robotic techniques and instruments. Total knee
      arthroplasties were performed on 10 pairs of fresh cadaveric femora. Ten knees
      were replaced using the robot-assisted minimally invasive technique and 10 using
      the conventional minimally invasive technique. After prosthesis implantation,
      limb and prosthesis alignments were investigated by measuring mechanical axis
      deviation, femoral and tibial sagittal and coronal inclination, and femoral
      rotational alignment with 3-dimensional computed tomography scans. Postoperative
      alignment accuracy of the implanted prostheses was better in the robot-assisted
      minimally invasive TKA group than in the conventional minimally invasive TKA
      group as judged by the rotational alignment of the femoral component (0.7 degrees
      +/-".3 degrees  vs 3.6 degrees +/-2.2 degrees , respectively) and the tibial
      component sagittal angle (7.8 degrees +/-1.1 degrees  vs 5.5 degrees +/-3.6
      degrees , respectively). One sagittal inclination outlier for the tibial side
      existed in the robotic minimally invasive TKA group, and 2 outliers for the
      mechanical axis, 2 for the tibial side sagittal inclination, and 2 for the
      femoral rotational alignment existed in the conventional minimally invasive TKA
      group. Higher implanted prostheses accuracy and fewer outliers in postoperative
      radiographic alignments can be attained with robot-assisted TKA. Minimally
      invasive TKA in combination with an improved robot-assisted technique is an
      alternative option to compensate for the shortcomings of conventional minimally
      invasive TKA.

PMID- 22955399
TI  - Internal fixation versus shoulder hemiarthroplasty for displaced 4-part proximal
      humeral fractures in elderly patients.
AB  - The purpose of this single-center, randomized, controlled trial was to report on
      the 2-year outcomes of proximal humerus fractures in elderly patients treated
      with open reduction and internal fixation (ORIF) with either a locking plate or
      shoulder hemiarthroplasty. Thirty-two patients (87% women) with a mean age of
      71.9 years (range, 67-86 years) were treated with ORIF with either a locking
      plate or shoulder hemiarthroplasty after shoulder injury. The main outcome
      measures were the Constant score, Disabilities of the Arm, Shoulder and Hand
      (DASH) score, and health-related quality of life (HRQoL) according to the EQ-5D
      (EuroQol Group, Rotterdam, The Netherlands). At final 2-year follow-up, DASH and
      pain scores favored the shoulder hemiarthroplasty group. Mean flexion was 129
      degrees  in the shoulder hemiarthroplasty group and 117 degrees  in the ORIF
      group (P=.27), and mean abduction was 123 degrees  in the shoulder
      hemiarthroplasty group and 111 degrees  in the ORIF group (P=.41). In the
      shoulder hemiarthroplasty group, the EQ-5D index score decreased from 0.85+/-0.21
      before injury to 0.65+/-0.14 at 4 months postoperatively. The score was 0.79+/
      0.24 at 12 months postoperatively and 0.81+/-0.17 at 24 months postoperatively.
      The results of this study indicate an advantage in functional outcomes and HRQoL
      favoring shoulder hemiarthroplasty compared with ORIF with a locking plate,
      although most outcomes were not significantly different.

PMID- 22955400
TI  - Early postoperative outcomes between arthroscopic and mini-open repair for
      rotator cuff tears.
AB  - The purpose of this study was to compare early postoperative outcomes between
      arthroscopic and mini-open repair for rotator cuff tears smaller than 3 cm to
      determine whether arthroscopic repair causes less postoperative pain and allows
      for faster recovery of range of motion. Sixty patients scheduled for rotator cuff
      repair were randomized to either an arthroscopic repair group (30 patients) or a
      mini-open repair group (30 patients). Pain level, range of motion, shoulder
      stiffness, and complications were compared between the 2 groups from immediately
      postoperatively to 6 months postoperatively. Although no statistically
      significant difference was found in mean visual analog scale pain scores between
      the 2 groups during the 6 months postoperatively, mean visual analog scale pain
      score was significantly lower in the arthroscopic repair group compared with the
      mini-open repair group at postoperative days 1 and 2 (P=.02 and P=.04,
      respectively). No significant difference existed in postoperative range of
      motion, duration of rehabilitation, shoulder stiffness, or complications between
      the 2 groups; however, the use of additional analgesics in the arthroscopic
      repair group was significantly lower than in the mini-open repair group (P=.03).
      Arthroscopic and mini-open repair had equivalent clinical outcomes in the early
      postoperative period. The hypothesis that arthroscopic repair would cause less
      postoperative pain and allow faster recovery of range of motion in the early
      postoperative period compared with mini-open repair was not supported.

PMID- 22955401
TI  - Pseudoparalysis: the importance of rotator cable integrity.
AB  - The purpose of this study was to clinically examine the relationship between
      rotator cable integrity and the presence of pseudoparalysis. A retrospective
      review was performed of a consecutive series of arthroscopic repairs of massive
      rotator cuff tears performed between January 2007 and June 2009. A total of 127
      massive tears were identified. Group 1 comprised 24 patients with preoperative
      pseudoparalysis. Group 2 comprised 97 patients (103 repairs) with active forward
      flexion more than 90 degrees . In group I, no patient maintained integrity of
      both rotator cable attachments; 1 rotator cable attachment was disrupted in 45.8%
      of cases; and both rotator cable attachments were disrupted in 54.2% of cases. In
      group II, both rotator cable attachments were intact in 22.3% of cases; 1 rotator
      cable attachment was disrupted in 62.1% of cases; and both rotator cable
      attachments were disrupted in 15.5% of cases. The difference in the distribution
      of cable attachments between the 2 groups was statistically significant (P<.001).
      Overall, preoperative pseudoparalysis predicted a disruption of both rotator
      cables with 88.8% specificity, 44.8% sensitivity, and 77.8% accuracy.
      Pseudoparalysis requires the disruption of at least 1 rotator cable attachment.
      This study reinforces the concept of rotator cable integrity and the ability of
      patients to maintain forward flexion above shoulder level and highlights the
      importance of reinforcing the rotator cable attachments in the repair of massive
      rotator cuff tears.

PMID- 22955402
TI  - Distal ulna hook plate fixation for unstable distal ulna fracture associated with
      distal radius fracture.
AB  - The significance of distal ulna fractures is often undermined, which can result
      in inadequate treatment compared with fractures of the radius, the ulna's larger
      counterpart. However, little guidance exists in the current literature on how to
      manage distal ulna head or neck fractures and intra-articular ulna head
      fractures. Therefore, the purpose of this retrospective study was to evaluate the
      outcomes of distal ulna hook plate fixation for the treatment of an unstable
      distal ulna fracture associated with a distal radius fracture. Twenty-five
      patients with unstable distal ulna fractures who underwent stable fixation for an
      associated distal radius fracture were included in the study. All patients
      achieved satisfactory reduction and bony union. Average final motion was as
      follows: wrist flexion, 72 degrees  (range, 60 degrees -85 degrees ); extension,
      69 degrees  (range, 65 degrees -80 degrees ); pronation, 77 degrees  (range, 55
      degrees -95 degrees ); supination, 82 degrees  (range, 65 degrees -90 degrees );
      ulnar deviation, 35 degrees  (range, 15 degrees -50 degrees ); and radial
      deviation, 24 degrees  (range, 10 degrees -40 degrees ). Average postoperative
      grip strength was 28 kg (range, 22-30 kg) and was 91% (range, 71%-100%) in the
      cases in which the dominant hand was injured and 80% (range, 65%-100%) in the
      cases in which the nondominant hand was injured. Average postoperative modified
      Mayo wrist score and Disabilities of the Arm, Shoulder and Hand score was 87
      points (range, 65-100 points) and 14 points (range, 0-54 points), respectively.
      Chronic instability of the distal radioulnar joint was not encountered in any
      patient. Thus, the study demonstrated that distal ulna hook plate fixation for
      the treatment of unstable distal ulna fractures can achieve healing with good
      alignment, satisfactory function, and minimal transient morbidity.

PMID- 22955403
TI  - Open release and a hinged external fixator for the treatment of elbow stiffness
      in young patients.
AB  - Elbow stiffness is a well-recognized complication following elbow trauma, but
      little information is available regarding the surgical treatment of elbow
      stiffness in children and adolescents. This article presents the results of open
      arthrolysis with twin incisions and a hinged external fixator to treat severe
      elbow contracture in children and adolescents. Twenty-one patients (mean age,
      14.9 years; range, 7-19 years) were evaluated. All patients underwent surgery
      using a hinged external fixator and a combined mediolateral approach to address
      the elbow contracture. Mayo elbow score and range of motion (ROM) were measured
      preoperatively and at 3, 12, and 24 months postoperatively. All but 1 patient
      achieved a functional ROM of 100 degrees . Preoperatively, mean flexion was 70.2
      degrees  (range, 30 degrees -100 degrees ), extension was 42.6 degrees  (range, 0
      degrees -80 degrees ), and total ROM was 28.5 degrees  (range, 0 degrees  to 80
      degrees ); postoperatively, mean flexion improved to 122.8 degrees  (range, 90
      degrees -140 degrees ), extension to 10 degrees  (range, 0 degrees -30 degrees ),
      and total ROM to 114.5 degrees  (range, 60 degrees -140 degrees ). The Mayo elbow
      score improved from a mean of 48 points (range, 35-65 points) to 90 points
      (range, 75-100 points), and 9 patients had excellent results, 7 had good results,
      4 had fair results, and 1 had a poor result. No significant differences existed
      between postoperative measurements at 3, 12, and 24 months. No pin-tract
      infections or deep infections occurred, and no vascular or neurological
      complications were noted. Surgical treatment of elbow stiffness using a hinged
      external fixator and open arthrolysis is an effective procedure in children and
      adolescents.

PMID- 22955404
TI  - Surgical management of sportsman's hernia in professional soccer players.
AB  - Soccer players frequently experience acute and chronic groin pain. Sportsman's
      hernia is a common injury in professional soccer players, that causes inguinal
      pain. The authors discuss their experience with the management of sportsman's
      hernia in professional soccer players competing in national and international
      competition in a retrospective review of prospectively collected data. Between
      March 2004 and December 2009, seventy-one professional soccer players were
      surgically treated for sportsman's hernia. Average age at surgery was 24 years,
      and average duration of symptoms from onset to surgical repair was 11 months.
      Conservative treatment improved symptoms temporarily or to some extent in 18
      athletes. All athletes underwent a bilateral open hernia repair with concurrent
      adductor tendon release. Average follow-up was 4 years, and average time to
      return to competitive sport was 4 months. At final follow-up, 95% of soccer
      players were still active, 48 at the same level and 19 at a lower level. Four
      athletes had stopped their careers because of another injury (n=2) or recurrence
      (n=2). Sportsman's hernia is a potentially career-ending injury in professional
      soccer players. Conservative management is often unsuccessful. An open surgical
      hernia repair combined with an adductor longus tenotomy relieves the symptoms
      caused by a sportsman's hernia and restores activity in 95% of athletes. This
      study offers insight into the management of sportsman's hernia and offers a
      successful treatment to salvage the careers of professional soccer players.

PMID- 22955405
TI  - Treatment of lower-extremity long-bone fractures in active, nonambulatory,
      wheelchair-bound patients.
AB  - A retrospective review of surgically treated lower-extremity long-bone fractures
      in wheelchair-bound patients was conducted. Between October 2000 and July 2009,
      eleven lower-extremity fractures in 9 wheelchair-bound patients underwent
      surgical fixation. The Short Musculoskeletal Function Assessment, Short Form, and
      Spinal Cord Injury Quality of Life questionnaires were used to assess functional
      outcome. Mechanism of injury for all patients was a low-energy fall that occurred
      while transferring. Four patients who sustained a distal femur fracture, 1
      patient who sustained a distal femur fracture and a subsequent proximal tibia
      fracture, and 1 patient who sustained a proximal third tibia shaft fracture
      underwent open reduction and internal fixation with plates and screws. Three
      patients with 4 midshaft tibia fractures underwent intramedullary nailing. At
      last follow-up, all 9 patients had returned to their baseline preoperative
      function. Quality of life was significantly higher (P<.01) than the Spinal Cord
      Injury Quality of Life questionnaire's reference score. Self-reported visual
      analog scale pain scores improved significantly from time of fracture to last
      follow-up (P=.02). All fractures achieved complete union, and no complications
      were reported. This study's findings demonstrate that operative treatment in
      active, wheelchair-bound patients can provide an improved quality of life
      postinjury and a rapid return to activities.

PMID- 22955406
TI  - Structural and biomechanical characteristics after early mobilization in an
      Achilles tendon rupture model: operative versus nonoperative treatment.
AB  - Acute Achilles tendon ruptures are common sports injuries; however, treatment
      remains a clinical challenge. Studies show a superior effect of early
      mobilization and full weight bearing on tendon healing and clinical outcome;
      however, few data exist on structural and biomechanical characteristics in the
      early healing phase. This study investigated the histological and biomechanical
      characteristics of early mobilization and full weight bearing in an Achilles
      tendon rupture model. Eighty rats underwent dissection of a hindpaw Achilles
      tendon; 40 rats were treated conservatively and 40 underwent open repair of the
      transected Achilles tendon by suturing. Early mobilization and full weight
      bearing were allowed in both groups. At 1, 2, 4, and 8 weeks after tenotomy,
      tensile strength, stiffness, thickness, tissue characteristics (histological
      analysis), and length were determined. Dissected Achilles tendons healed in all
      animals during full weight-bearing early mobilization. One and 2 weeks after
      tenotomy, rats in the operative group showed increased tensile strength and
      stiffness compared with the nonoperative group. Repair-site diameters were
      increased at 1, 2, and 8 weeks after tenotomy. Tendon length was decreased in the
      operative group throughout observation, whereas the nonoperative group showed
      increased structural characteristics on the cellular level and a more homogeneous
      collagen distribution. Surgical treatment of dissected rat Achilles tendons
      showed superior biomechanical characteristics within the first 2 weeks.
      Conservative treatment resulted in superior histological findings but significant
      lengthening of the tendon in the early healing phase (weeks 1-8).

PMID- 22955407
TI  - Preoperative embolization significantly decreases intraoperative blood loss
      during palliative surgery for spinal metastasis.
AB  - Several studies have evaluated the efficacy of preoperative embolization in
      devascularizing tumors. However, no study has measured intraoperative blood loss
      in a single palliative surgery compared with a control group without preoperative
      embolization. The purpose of this retrospective study was to evaluate the
      efficacy of preoperative embolization on intraoperative blood loss in palliative
      decompression and instrumented surgery using a posterior approach for spinal
      metastasis. Between 2000 and 2010, forty-six patients underwent palliative
      decompression and instrumented surgery using a posterior approach for spinal
      metastasis in the thoracic and lumbar spine. Preoperative embolization was
      performed in 23 patients (embolization group), and surgery was performed within 3
      days after embolization. The embolic materials used were polyvinyl alcohol
      particles, gelatin sponge, and metallic coils. Twenty-three patients did not
      undergo embolization (no embolization group). Pain and neurologic symptoms in all
      46 patients were relieved postoperatively. Average intraoperative blood loss was
      520 mL (range, 140-1380 mL) in the embolization group and 1128 mL (range, 100
      3260 mL) in the no embolization group (P<.05). In the embolization group,
      intraoperative blood loss was not correlated with the degree of tumor
      vascularization, completeness of embolization, or time between embolization and
      surgery. Intraoperative blood loss after preoperative embolization was less than
      half that after no preoperative embolization.

PMID- 22955408
TI  - Surgical management of congenital cervical kyphosis.
AB  - Congenital cervical kyphosis is a rare clinical condition. The purpose of this
      study was to review the surgical management and outcomes of 12 consecutive cases
      of congenital cervical kyphosis management by the same surgical team. The authors
      retrospectively analyzed the records of 12 patients (5 men and 7 women) with an
      average age of 18.4 years (range, 15-31 years) who underwent surgery for
      congenital cervical kyphosis at the authors' institution between 2001 and 2005.
      All patients had congenital cervical kyphosis; those with secondary kyphosis
      deformity due to causes such as infection, tumors, and surgery were excluded. The
      indications for surgery were signs of spinal cord compression with progression of
      clinical symptoms such as decreased muscle strength and paresthesia. All patients
      had radiographic evidence of cervical kyphosis. Six patients underwent anterior
      decompression, autogenous bone grafting, and instrumentation, and the other 6
      patients underwent combined anterior-posterior surgery. All surgeries were
      performed successfully with no complications. Bone graft fusion occurred in 11
      patients. In 1 patient who underwent anterior surgery, the bone graft was partly
      absorbed, and pseudarthrosis was noted at 3 years postoperatively. Mean Japan
      Orthopaedic Association cervical myelopathy score and mean Cobb angle were
      significantly improved at 1 week and 1 year postoperatively compared with
      preoperative values. Anterior and combined anterior-posterior surgical approaches
      are useful for the correction of congenital cervical kyphosis. Bone graft fusion
      is also critical for maintaining the surgical correction. Choice of surgical
      methods depends on the patient's clinical condition.

PMID- 22955409
TI  - Sustained delivery of BMP-2 and platelet-rich plasma-released growth factors
      contributes to osteogenesis of human adipose-derived stem cells.
AB  - Platelet-rich plasma (PRP) has a pool of multiple growth factors efficient at
      inducing the proliferation and osteogenic differentiation of human adipose
      derived stem cells (hADSCs). Bone morphogenetic protein (BMP)-2 is a strong
      stimulator for the osteogenic differentiation of hADSCs. The purpose of this
      study was to verify the effect of PRP-released growth factors and microsphere
      encapsulated BMP-2 on the proliferation and osteoblastic differentiation of
      hADSCs and to construct a novel tissue-engineered bone. The BMP-2-loaded
      microspheres and hADSCs were embedded in activated PRP gel. Another 5 composites
      (hADSCs/platelet-poor plasma [PPP]; hADSCs/PRP; hADSCs/BMP-2/PPP; hADSCs/BMP
      2/PRP; and hADSCs/BMP-2+microspheres/PPP) were also constructed. The DNA content,
      alkaline phosphatase activity, mRNA expression of alkaline phosphatase,
      osteopontin, osteocalcin, and mineralization of hADSCs in each composite were
      compared. The DNA content was higher in all PRP-containing composites, meaning
      that PRP-released growth factors stimulated proliferation of hADSCs. Alkaline
      phosphatase increased in BMP-2/PRP and BMP-2+microspheres/PRP composites in the
      first 7 days, meaning that BMP-2 had a synergistic effect with PRP in the early
      differentiation of hADSCs. Osteopontin, osteocalcin, and mineralization assays
      were higher in BMP-2+microspheres/PRP composite than in the BMP-2/PRP composite
      up to 21 days, meaning that a continuous delivery of BMP-2 stimulates
      osteoblastic differentiation of hADSCs at the early stage and the final
      maturation stage. These results suggest that sustained delivery of BMP-2 in
      combination with PRP is better than a single administration of PRP or BMP-2 in
      the osteogenic differentiation of hADSCs.

PMID- 22955410
TI  - Characteristics and impact of animal models used for sports medicine research.
AB  - Animal models are commonly used for translational research despite evidence that
      the methodology of these studies is often inconsistent and substandard. This
      study describes the characteristics and impact of published research using animal
      models in the American Journal of Sports Medicine (AJSM). Peer-reviewed articles
      published in the AJSM between January 1990 and January 2010 using animal models
      were identified using MEDLINE. The articles were reviewed for funding source,
      anesthesia used, animal used, study type, study location, outcome measures,
      number of animals, duration of animal survival, main topic being studied, and
      positive or negative treatment effect. The impact factor of the studies published
      between 2005 and 2010 was calculated. Two hundred fifty-seven articles, or 6%
      (257/4278) of the total publications during the 20-year period, were analyzed.
      The impact factor increased from 1.83 in 2005 to 3.9 in 2010. The most common
      animals used were rabbits (24%) and pigs (16%). The anterior cruciate ligament
      was studied in 34% of the articles, and a pig model was used for 31% of these
      studies. Eighty-six percent of the studies had a positive treatment effect. This
      study shows that animal models used in sports medicine research lack uniformity
      in their methods and suggests that a publication bias may exist for animal
      research in the sports medicine literature.

PMID- 22955411
TI  - Level of evidence gap in orthopedic research.
AB  - Level of evidence is the most widely used metric for the quality of a
      publication, but instances exist in which a Level I study is neither feasible nor
      desirable. The goal of this study was to evaluate the level of evidence gap in
      current orthopedic research, which the authors defined as the disparity between
      the level of evidence that would be required to optimally answer the primary
      research question and the level of evidence that was actually used. Five
      orthopedic surgeons (K.D.B., J.B., J.A., S.D.M., W.N.S.) evaluated blinded
      articles from the first 6 months of 2010 in the Journal of Bone and Joint Surgery
      (American Volume) (JBJS-Am), classifying the study type and design and extracting
      a primary research question from each article. Each evaluator then defined the
      study type and method, along with the level of evidence that would ideally be
      used to address the primary research question. The level of evidence gap was then
      calculated by subtracting the actual level of evidence of the manuscript from the
      level of evidence of the idealized study. Of the 64 JBJS-Am manuscripts eligible
      for analysis, the average level of evidence was between Level II and III (mean,
      2.73). The average level of evidence gap was 1.06 compared with the JBJS-Am
      designated level of evidence and 1.28 compared with the evaluators' assessment.
      Because not all questions require Level I studies, level of evidence alone may
      not be the best metric for the quality of orthopedic surgery literature. Instead,
      the authors' concept of a level of evidence gap may be a better tool for
      assessing the state of orthopedic research publications.

PMID- 22955412
TI  - Prevalence of answers to orthopaedic in-training examination questions in 3
      commonly used orthopedic review sources.
AB  - One of the greatest predictors for resident success on the Orthopaedic In
      Training Examination (OITE) is reviewing previous OITE questions. However, no
      studies have examined which review sources contain the most answers to previously
      asked OITE questions. The goal of this study was to determine which review source
      contains the most answers to previously asked OITE questions. Each question from
      the 2006 to 2010 OITEs was examined. The questions were placed into 1 of 13
      categories based on their topic. The publication date of the recommended readings
      associated with each question was recorded. The answer to each question was then
      searched for in 3 commonly used review sources: Miller's Review of Orthopaedics,
      5th edition (MRO), American Academy of Orthopaedic Surgeons Comprehensive
      Orthopaedic Review (COR), and www.orthobullets.com (OB). Searchable electronic
      versions of each textbook were used, and each question had a 12-minute time
      limit. Of 1358 questions, 665 (49%) were found in all 3 sources. Significantly
      more answers were found on OB (99.4%) compared with MRO (60%) and COR (62%)
      (P<.0001). Significantly more answers to questions in each question category were
      found on OB compared with MRO or COR (P<.0001). More than 50% of all recommended
      readings for OITE questions were published within 5 years of the OITE. Residents
      using OB to review for the OITE will be exposed to significantly more answers of
      previously asked OITE questions than residents using MRO or COR (P<.0001).

PMID- 22955413
TI  - Total volar extrusion of the lunate and scaphoid proximal pole with concurrent
      scapholunate dissociation.
AB  - This article describes a case of a 24-year-old man with a total volar extrusion
      of the lunate and scaphoid proximal pole with concurrent scapholunate
      dissociation. The viability of the lunate and the proximal pole of the scaphoid
      are at high risk in this type of injury. Scaphoid nonunion, avascular necrosis of
      the lunate and proximal pole of the scaphoid, and carpal instability are
      inevitable unless the blood supply is restored. Thus, proximal row carpectomy at
      injury may be an acceptable option to avoid these complications and late
      sequelae, including chronic wrist pain and dysfunction. However, the authors
      attempted accurate reduction of the extruded bones and internal fixation.Final
      radiographs and magnetic resonance imaging 12 years postoperatively showed
      healing without avascular necrosis. Carpal indices involving the scapholunate
      angle, radiolunate angle, and carpal height ratio were similar in both wrists
      without evidence of carpal instability or collapse. Range of motion and grip
      power were 75% and 76%, respectively, compared with those of the uninjured wrist.
      Clinical scores showed good results, and the patient reported no pain during
      activities of daily living and was satisfied with his surgical results. Open
      reduction and internal fixation can be a viable option in this rare pattern of
      injury.

PMID- 22955414
TI  - Bilateral extensor digitorum brevis manus.
AB  - Dorsal wrist pain and swelling is commonly attributed to a dorsal wrist ganglion.
      However, based on the authors' experience, a cautious surgeon should keep the
      uncommonly symptomatic diagnosis of an extensor digitorum brevis manus in their
      differential despite classic ganglion presentation and suggestive advanced
      imaging. This article describes a case of a young patient who presented with
      bilateral symptomatic extensor digitorum brevis manus anomalies that required
      surgical intervention. An extensor digitorum brevis manus is present in 3% of the
      population in a classic anatomy study from Japan and is most commonly symptomatic
      with heavy activity and extremes of wrist extension. Anatomically, the extensor
      digitorum brevis manus is located in the fourth wrist compartment and most
      commonly inserts on the index finger extensor mechanism. Examination often
      reveals a spindle-shaped mass that is palpable distal to the extensor mechanism
      and moves with extensor tendon motion. Magnetic resonance imaging shows a typical
      dorsal mass distal to the common extensors with a similar signal as muscle with
      all image sequencing. Treatment includes activity alterations to relieve symptoms
      or surgical excision of the muscle belly for refractory cases with care taken to
      preserve the index extensor mechanism.

PMID- 22955415
TI  - Rare massive osteolipoma in the upper part of the knee in a young adult.
AB  - Lipoma is a common benign soft tissue tumor. This article describes a massive
      osteolipoma, an unusual lipoma that is fixed to the femoral periosteum. A 21-year
      old man presented with a subcutaneous mass at the knee region, which had been
      present for more than 36 months, and a slight limitation of joint flexibility. On
      physical examination, a mass approximately 12*6*2 cm(3) in dimension was palpable
      beneath the skin at the knee proximal medial area when the knee was in flexion.
      The mass was ovoid, hard, nontender, well demarcated, large, subcutaneous, and
      relatively fixed to the femur. Medical imaging examination showed that the femur
      had a well-demarcated mass with a basement. No prominent body weight loss was
      noted. The excisional mass of 16*12*10 cm(3) was not well encapsulated by a thin,
      fibrous membrane and had an apparently osseous basal portion. Intraoperative
      rapid frozen section revealed that the tumor was derived from the adipose cells.
      The postoperative course was uneventful. The definitive pathologic diagnosis was
      intermuscular osteolipoma without evidence of malignancy. No recurrence was
      observed at 6-month follow-up. Osteolipoma with independent bone and an osseous
      basal portion is rare, especially in young adults. Osteolipoma has the same
      prognosis as simple lipoma, and surgical excision is the recommended treatment.
      To the authors' knowledge, such a massive osteolipoma has not been reported.

PMID- 22955416
TI  - Fracture of an osteochondroma of the femoral neck caused by impingement against
      the ischium.
AB  - This article describes 2 cases of osteochondroma emanating from the posterior
      aspect of the femoral neck with a fracture at the base of its stalk caused by
      impingement between the tumor and the ischium. A 44-year-old man and a 57-year
      old man presented with left hip pain. Radiographs revealed a mass at the
      posterior aspect of the femoral neck. Computed tomography and magnetic resonance
      imaging revealed that the mass was fractured at the stalk. The relationship
      between the tumor and the ischium was examined with an image intensifier. The
      tumor impinged on the ischium with slight flexion and external rotation of the
      hip joint. In both patients, the tumor was excised, and the pathological report
      was osteochondroma. At follow-up, the patients had full hip joint range of
      motion, and lateral radiographs of the left hip joint showed complete resection
      of the tumor without recurrence. To the authors' knowledge, the current cases are
      the first reports of fracture of an osteochondroma with confirmed impingement
      using an image intensifier pre- and intraoperatively. Both patients had histories
      of restricted hip range of motion and a sudden onset of pain. After excision, the
      patients recovered to activities of daily living with no complications. An
      osteochondroma at the posterior aspect of the femoral neck can impinge on the
      ischium and fracture at its base with a sudden onset of pain. Awareness of this
      mechanism of impingement may lead to a better understanding of patient symptoms
      caused by osteochondroma of the femoral neck.

PMID- 22955417
TI  - Adductor insertion avulsion syndrome mimicking neoplastic processes in a 14-year
      old long-distance runner.
AB  - Adductor insertion avulsion syndrome, also known as thigh splints, is an uncommon
      condition that can mimic primary bone tumors or osteomyelitis. This article
      describes the clinical and imaging findings of adductor insertion avulsion
      syndrome in a 14-year-old male long-distance runner. The patient presented with a
      1-month history of progressively worsening pain in the medial aspect of the left
      thigh. No significant findings were noted on physical examination except slight
      tenderness to palpation. Radiographs revealed an intracortical radiolucent lesion
      with a solid periosteal reaction in the medial aspect of the femoral diaphysis.
      Bone scintigraphy showed an increased uptake corresponding with the lesion of the
      left medial femoral diaphysis. Computed tomography confirmed the presence of
      periosteal reaction and intracortical linear hypoattenuation and showed no
      fracture line. Magnetic resonance imaging revealed periosteal, cortical, and
      intramedullary signal intensity abnormalities. These clinical and radiologic
      features suggested adductor insertion avulsion syndrome. The patient was treated
      with initial avoidance of weight bearing using 2 crutches for ambulation,
      followed by progressive weight bearing over a period of 2 weeks. The symptom
      resolved completely 7 weeks after initial evaluation, and the patient had normal
      gait without pain. Knowledge of this condition is important for the appropriate
      interpretation of imaging findings and the avoidance of unnecessary biopsy with
      potentially misleading results. Moreover, this case provides a time line as a
      reference for the rehabilitation of patients in similar cases.

PMID- 22955418
TI  - Selective computed tomography-guided perisciatic injection as a diagnostic tool
      in multiple hereditary exostoses.
AB  - Multiple osteochondromas, also known as multiple hereditary exostoses, is an
      autosomal-dominant disease. Multiple osteochondromas are characterized by the
      development of cartilage-capped bony tumors, known as osteochondromas.
      Osteochondromas can cause limb deformities, limb-length discrepancies, angular
      deformations, bursitis, and impingement of adjacent tendons or neurovascular
      structures. They have also been reported as a cause of sciatic pain. Sometimes,
      more than 1 location of neural compression exists, thereby presenting a difficult
      diagnostic challenge for treating physicians. This article describes a patient
      with multiple hereditary exostoses and accompanying severe sciatic pain who was
      referred for a revision decompressive spine surgery. The patient's functional
      impairment was such that he was unable to sit for a few minutes. A selective
      computed tomography-guided perisciatic nerve injection was performed to
      differentiate between lateral spinal stenosis and peripheral nerve compression or
      impingement by an existing large pelvic osteochondroma. The patient reported
      substantial relief and regained the ability to sit pain free immediately
      postoperatively. Excision of a proximal femur osteochondroma was performed based
      on the results of a selective perisciatic nerve injection, resulting in
      successful resolution of his sciatic pain and functional impairment. The current
      case is an example of the diagnostic challenge in treating patients with multiple
      anatomic lesions that can cause symptoms and demonstrate how selective computed
      tomography-guided perisciatic nerve injection can aid clinicians in obtaining an
      accurate diagnosis and choosing the most appropriate surgical management.

PMID- 22955419
TI  - Athletic cervical spine injury in the setting of fusion failure of the anterior
      and posterior atlas.
AB  - This article describes a rare congenital abnormality of anterior and posterior C1
      fusion failure presenting after an acute athletic injury to the fibrous nonunion.
      C1 congenital malformations are rare, occurring in approximately 2% of patients;
      even rarer are combined anterior and posterior arch malformations in the same
      patient. Posterior ring abnormalities are more common than anterior ring injuries
      (4.5:1, respectively). To the authors' knowledge, combined anterior and posterior
      ring congenital malformations with subsequent injury have not been previously
      described. In the current patient, a congenital failure of fusion of the anterior
      and posterior arches of C1 was identified. The anterior fibrous nonunion was
      injured while the patient played football, leading to transient neurologic injury
      and dysphagia from soft tissue swelling. The patient was initially diagnosed with
      an acute fracture at another facility; however, given advanced imaging, flexion
      and extension views, and a normal neurologic examination, the authors diagnosed a
      traumatized congenital defect. The injury healed with a short period of cervical
      collar immobilization and supportive measures. Such malformations are usually
      found incidentally, but they can be symptomatic after trauma. Images to
      distinguish these deficits can be difficult because the differences between
      chronic nonunions and congenital malformations are subtle. Surgery is rarely
      indicated for congenital malformations because they are often stable even after
      injury; however, they may predispose patients to neurologic injury in the future
      with high-risk activities. Because the current patient had an increased chance of
      future injury secondary to the lack of bone formation in the C1 vertebrae, he was
      restricted from participating in contact sports.

PMID- 22955420
TI  - Evolving compartment syndrome detected by loss of somatosensory- and motor-evoked
      potential signals during cervical spine surgery.
AB  - Neurologic injury is a rare but devastating complication of spinal surgery that
      can result in mild sensory to severe motor deficits. Surgeons increasingly use
      electrophysiological spinal cord function monitoring, including somatosensory-
      and motor-evoked potentials, intraoperatively to provide information about spinal
      cord function, aid in surgical decision making, improve outcomes, and reduce
      complication rates. By providing real-time information about the dorsal and
      anterior motor column function, somatosensory- and motor-evoked potentials
      signals allow surgeons to reverse noticeable changes and avoid devastating
      neurologic injuries. Recognizing changes in baseline signals in the setting of
      known risk factors enables surgeons to correct these risks. This article
      describes a case in which somatosensory- and motor-evoked potentials monitoring
      were lost in the setting of an impending right forearm compartment syndrome
      during 2-level anterior cervical diskectomy and fusion. To the authors'
      knowledge, this is the first reported case of spinal cord monitoring detecting an
      evolving compartment syndrome during cervical spine surgery. The early changes in
      signal intensity enabled the surgeon to search for a cause and remedy the
      situation by removing the infiltrated intravenous line. Without the observed
      changes in somatosensory- and motor-evoked potentials, it is likely that the
      compartment syndrome may have progressed to the point of requiring fasciotomy to
      prevent lasting neuromuscular injury. This article describes a new cause of
      changes in electrophysiological monitoring and further displays the usefulness of
      somatosensory- and motor-evoked potentials monitoring during even routine spinal
      surgery.

PMID- 22955421
TI  - Spontaneous hemorrhage in an upper lumbar synovial cyst causing subacute cauda
      equina syndrome.
AB  - Lumbar spine synovial cysts are becoming more frequent, and they are generally
      associated with degenerative lumbar spinal disease. They are common in lower
      lumbar lesions but rare in upper lumbar lesions. Several cases of hemorrhage into
      lower lumbar juxtafacet cysts after trauma or anticoagulation therapy have been
      reported in the literature. This article describes a case of subacute cauda
      equina syndrome resulting from spontaneous hemorrhage into an upper lumbar
      synovial cyst. A 65-year-old man presented with a 3-month history of intermittent
      bilateral lumbar pain. One week before, he experienced a sudden exacerbation of
      lumbar pain and began falling frequently; he also reported weakness and tingling
      in his lower limbs. A hematic collection associated with a large juxtafacet cyst
      at L2-L3 was suspected on magnetic resonance imaging. He underwent surgical
      decompression, and the cyst was resected. Microscopic examination was consistent
      with the diagnosis of a synovial cyst. Two days postoperatively, he was walking
      independently. Although several descriptions exist of hemorrhagic lumbar
      juxtafacet cysts after trauma or anticoagulant therapy, to the authors'
      knowledge, this is the first documented case of hemorrhage in an upper lumbar
      synovial cyst with no previous traumatic event or medication use. Magnetic
      resonance imaging was essential in making the preoperative diagnosis. Surgical
      removal of the cyst was an effective treatment.

PMID- 22955422
TI  - Computational study of EGFR inhibition: molecular dynamics studies on the active
      and inactive protein conformations.
AB  - The structural diversity observed across protein kinases, resulting in subtly
      different active site cavities, is highly desirable in the pursuit of selective
      inhibitors, yet it can also be a hindrance from a structure-based design
      perspective. An important challenge in structure-based design is to better
      understand the dynamic nature of protein kinases and the underlying reasons for
      specific conformational preferences in the presence of different inhibitors. To
      investigate this issue, we performed molecular dynamics simulation on both the
      active and inactive wild type epidermal growth factor receptor (EGFR) protein
      with both type-I and type-II inhibitors. Our goal is to better understand the
      origin of the two distinct EGFR protein conformations, their dynamic differences,
      and their relative preference for Type-I inhibitors such as gefitinib and Type-II
      inhibitors such as lapatinib. We discuss the implications of protein dynamics
      from a structure-based design perspective.

PMID- 22955423
TI  - Molecular dynamics simulations reveal structural instability of human trypsin
      inhibitor upon D50E and Y54H mutations.
AB  - Serine protease inhibitor Kazal type 1 (SPINK1) plays an important role in
      protecting the pancreas against premature trypsinogen activation that causes
      pancreatitis. Various mutations in the SPINK1 gene were shown to be associated
      with patients with pancreatitis. Recent transfection studies identified
      intracellular folding defects, probably caused by mutation induced misfolding of
      D50E and Y54H mutations, as a common mechanism that reduces SPINK1 secretion and
      as a possible novel mechanism of SPINK1 deficiency associated with chronic
      pancreatitis. Using molecular dynamics, we investigated the effects of D50E and
      Y54H mutations on SPINK1 dynamics and conformation at 300 K. We found that the
      structures of D50E and Y54H mutants were less stable than and were distorted from
      those of the wild type, as indicated by the RMSD plots, RMSF plots and DSSP
      series. Specifically, unwinding of the top of helices (the main secondary
      structures) and the distortion of the loops above the helices were observed. It
      may be possible that this distorted protein structure may be recognized as "non
      native" by members of the chaperone family; it may be further retained and
      targeted for degradation, leading to SPINK1 secretion reduction and subsequently
      pancreatitis in patients as Kiraly et al. (Gut 56:1433, 2007) proposed.

PMID- 22955424
TI  - A B3LYP and MP2(full) theoretical investigation into the strength of the C-NO(2)
      bond upon the formation of the intermolecular hydrogen-bonding interaction
      between HF and the nitro group of nitrotriazole or its methyl derivatives.
AB  - The changes of bond dissociation energy (BDE) in the C-NO(2) bond and nitro group
      charge upon the formation of the intermolecular hydrogen-bonding interaction
      between HF and the nitro group of 14 kinds of nitrotriazoles or methyl
      derivatives were investigated using the B3LYP and MP2(full) methods with the 6
      311++G**, 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. The strength of the C
      NO(2) bond was enhanced and the charge of nitro group turned more negative in
      complex in comparison with those in isolated nitrotriazole molecule. The
      increment of the C-NO(2) bond dissociation energies correlated well with the
      intermolecular H-bonding interaction energies. Electron density shifts analyses
      showed that the electron density shifted toward the C-NO(2) bond upon complex
      formation, leading to the strengthened C-NO(2) bond and the possibly reduced
      explosive sensitivity.

PMID- 22955425
TI  - Correlation between substituent constants and hyperpolarizabilities for di
      substituted trans-azobenzenes.
AB  - Nonlinear optical properties of a series of disubstituted trans-azobenzenes were
      studied. The structures were fully optimized by B3LYP/6-31+G* and both static
      polarizabilities and hyperpolarizabilities were then calculated by the derivative
      method. In order to show the relationships between dipole moments,
      (hyper)polarizabilities and the structures, three kinds of substituent constants
      were applied to correlate with both ground state dipole moment and
      hyperpolarizabilities. Both physical properties have a satisfactory correlation
      with substituent constants Sigmasigma(+/-) and bond length alternation. Overall,
      the electronic excitation contribution to the hyperpolarizabilities is
      rationalized in terms of the two-level model.

PMID- 22955426
TI  - Hormonal contraceptive use and persistent Staphylococcus aureus nasal carriage.
AB  - BACKGROUND: Human nares colonized with Staphylococcus aureus are the most
      important reservoir for this pathogen. We studied the influence of sex and
      hormonal contraceptive use on persistent S. aureus nasal carriage. METHODS: We
      conducted a cohort study in healthy volunteers and determined carriage status at
      baseline and again at follow-up by using the results of 2 swab samples at each
      time point. We applied logistic regression to analyze associations of interest.
      RESULTS: At baseline, 266 of 1180 volunteers (22.5%) were classified as
      persistent nasal carriers. Compared with women not using hormonal contraceptives,
      women taking reproductive hormones (odds ratio [OR]. 1.88; 95% confidence
      interval [CI], 1.29-2.75; P = .001) and men (OR., 1.57; 95% CI, 1.08-2.28; P =
      .02) were more likely to be persistent carriers. These associations remained
      stable after adjusting for known risk factors of nasal carriage. Women taking
      hormonal contraceptives and being persistent carriers at baseline were more
      likely to remain carriers after a median follow-up time of 70 days than women not
      using such medication (OR, 3.25; 95% CI, 1.44-7.34; P = .005). No patterns of
      association could be observed between persistent carriage among women and type of
      progestin or dose of estrogen used. Assuming causality and using estimates from
      multivariable logistic regression, we approximated that 20% (95% CI, 2.4%-34.9%)
      of persistent nasal carriage among women represented by our sample is
      attributable to hormonal contraception (population-attributable fraction).
      CONCLUSIONS: The widespread use of hormonal contraception may substantially
      increase the human S. aureus reservoir with potential impact on S. aureus
      infection and transmission.

PMID- 22955427
TI  - Single nucleotide polymorphisms in ABCC2 associate with tenofovir-induced kidney
      tubular dysfunction in Japanese patients with HIV-1 infection: a pharmacogenetic
      study.
AB  - BACKGROUND: Tenofovir is a widely used antiretroviral drug although it can cause
      kidney tubular dysfunction (KTD). The aim of this study was to determine the
      association between polymorphisms in genes encoding drug transporters and KTD in
      Japanese patients treated with tenofovir. METHODS: The association between
      tenofovir-induced KTD and 14 single nucleotide polymorphisms (SNPs) in the ABCC2,
      ABCC4, ABCC10, SCL22A6, and ABCB1 genes was investigated in 190 Japanese
      patients. KTD was diagnosed by the presence of at least 3 abnormalities in the
      following parameters: fractional tubular resorption of phosphate, fractional
      excretion of uric acid, urinary beta2-microglobulin, urinary alpha1
      microglobulin, and urinary N-acetyl-beta-D-glucosaminidase. Genotyping was
      performed by allelic discrimination using TaqMan 5'-nuclease assays with standard
      protocols. Associations between genotypes and KTD were tested by univariate and
      multivariate logistic regression analyses. RESULTS: KTD was diagnosed in 19 of
      the 190 (10%) patients. Univariate and multivariate analyses showed a significant
      association between KTD and genotype CC at position -24 CC (adjusted odds ratio
      [OR], 20.08; 95% confidence interval [CI], 1.711-235.7; P= .017) and genotype AA
      at position 1249 (adjusted OR, 16.21; 95% CI, 1.630-161.1; P= .017) of ABCC2.
      Multivariate analysis showed higher adjusted OR for patients with both
      homozygotes (adjusted OR, 38.44; 95% CI, 2.051-720.4; P= .015). ABCC2 haplotype 
      24T and 1249G was a protective haplotype for KTD (OR, 0.098; 95% CI, .002-.603;
      P= .003 CONCLUSIONS: This is the first study of our knowledge to identify the
      association between SNPs in ABCC2 and tenofovir-induced KTD in an Asian
      population. Close monitoring of renal function is warranted in tenofovir-treated
      patients with these SNPs.

PMID- 22955428
TI  - Use of the correlation coefficient to compare a point-of-care antigen test
      against a quantitative sandwich enzyme-linked immunosorbent assay for the
      detection of cryptococcal meningitis.

PMID- 22955429
TI  - The effect of a "universal antiretroviral therapy" recommendation on HIV RNA
      levels among HIV-infected patients entering care with a CD4 count greater than
      500/MUL in a public health setting.
AB  - BACKGROUND: On 1 January 2010, a large, publicly funded clinic in San Francisco
      announced a "universal ART" approach to initiate antiretroviral therapy (ART) in
      all human immunodeficiency virus (HIV)-infected persons. The effect of changing
      guidance on real-world patient outcomes has not been evaluated. METHODS: We
      evaluated untreated adult patients (defined as going >90 days without ART use)
      visiting clinic from 2001 to 2011. The cumulative incidence of HIV RNA
      suppression (viral load, <500 copies/mL), stratified by CD4 cell count at entry
      and calendar dates representing guideline issuance, were estimated using a
      competing risk framework. A multivariate Poisson-based model identified factors
      associated with HIV RNA suppression 6 months after clinic entry. RESULTS: Of 2245
      adults, 87% were male, and the median age was 39 years (interquartile range, 33
      45 years). In 534 patients entering clinic with a CD4 cell count of >500
      cells/uL, the 1-year incidence of HIV RNA suppression was 10.1% (95% confidence
      interval [CI], 6.6%-14.6%) before 4 April 2005; 9.1% (95% CI, 3.6%-17.4%) from 4
      April 2005 to 1 December 2007; 14.1% (95% CI, 7.5%-22.8%) from 1 December 2007 to
      the universal ART recommendation and 52.8% (95% CI, 38.2%-65.4%) after. After
      adjustment, the SFGH policy was associated with a 6-fold increase in the
      probability of HIV RNA suppression 6 months after clinic entry. CONCLUSIONS:
      Recommendations to initiate ART in all HIV-infected patients increased the rate
      of HIV RNA suppression for patients enrolling in care with a CD4 cell count of
      >500 cells/uL and may foreshadow national trends given the March 2012 revision of
      national treatment guidelines to favor ART initiation for persons with CD4 cell
      counts of >500 cells/uL.

PMID- 22955430
TI  - Safety and effectiveness of meropenem in infants with suspected or complicated
      intra-abdominal infections.
AB  - BACKGROUND: Intra-abdominal infections are common in young infants and lead to
      significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial
      with excellent activity against pathogens associated with intra-abdominal
      infections. The purpose of this study was to determine the safety and
      effectiveness of meropenem in young infants with suspected or complicated intra
      abdominal infections. METHODS: Preterm and term infants <91 days of age with
      suspected or confirmed intra-abdominal infections hospitalized in 24 neonatal
      intensive care units were studied in an open-label, multiple-dose study. Adverse
      events and serious adverse events were collected through 3 and 30 days following
      the last meropenem dose, respectively. Effectiveness was assessed by 3 criteria:
      death, bacterial cultures, and presumptive clinical cure score. RESULTS: Of 200
      subjects enrolled in the study, 99 (50%) experienced an adverse event, and 34
      (17%) had serious adverse events; no adverse events were probably or definitely
      related to meropenem. The most commonly reported adverse events were sepsis (6%),
      seizures (5%), elevated conjugated bilirubin (5%), and hypokalemia (5%). Only 2
      of the serious adverse events were determined to be possibly related to meropenem
      (isolated ileal perforation and an episode of fungal sepsis). Effectiveness was
      evaluable in 192 (96%) subjects, and overall treatment success was 84%.
      CONCLUSIONS: Meropenem was well tolerated in this cohort of critically ill
      infants, and the majority of infants treated with meropenem met the definition of
      therapeutic success. CLINICAL TRIALS REGISTRATION: NCT00621192.

PMID- 22955431
TI  - Association between corticosteroids and infection, sepsis, and infectious death
      in pediatric acute myeloid leukemia (AML): results from the Canadian infections
      in AML research group.
AB  - BACKGROUND: Infection continues to be a major problem for children with acute
      myeloid leukemia (AML). Objectives were to identify factors associated with
      infection, sepsis, and infectious deaths in children with newly diagnosed AML.
      METHODS: We conducted a retrospective, population-based cohort study that
      included children <= 18 years of age with de novo, non-M3 AML diagnosed between
      January 1995 and December 2004, treated at 15 Canadian centers. Patients were
      monitored for infection from initiation of AML treatment until recovery from the
      last cycle of chemotherapy, conditioning for hematopoietic stem cell
      transplantation, relapse, persistent disease, or death (whichever occurred
      first). Consistent trained research associates abstracted all information from
      each site. RESULTS: 341 patients were included. Median age was 7.1 years
      (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26
      (7.6%) experienced death as a first event. There were 1277 courses of
      chemotherapy administered in which sterile site microbiologically documented
      infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred
      in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of
      corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression
      analysis, duration of corticosteroid exposure was significantly associated with
      more microbiologically documented sterile site infection, bacteremia, fungal
      infection, and sepsis. The only factor significantly associated with infectious
      death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence
      interval, 1.02-1.08; P = .001). CONCLUSIONS: In pediatric AML, infection, sepsis,
      and infectious death were associated with duration of corticosteroid exposure.
      Corticosteroids should be avoided when possible for this population.

PMID- 22955433
TI  - Editorial commentary: effectiveness or efficacy: which study to evaluate
      antibiotics in neonates?

PMID- 22955434
TI  - Editorial commentary: a syphilis wish list: better data, better tests.

PMID- 22955435
TI  - Response to pegylated interferon plus ribavirin among HIV/hepatitis C virus
      coinfected patients with compensated liver cirrhosis.
AB  - BACKGROUND: The objective of this study was to determine the efficacy of
      pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency
      virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated
      liver cirrhosis, as well as the predictors of response in these individuals.
      METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected
      patients who received peg-IFN and RBV and who had a liver biopsy or a liver
      stiffness measurement within the year before starting peg-IFN plus RBV were
      included in this study. The sustained virologic response (SVR) rate and
      predictors of SVR response were analyzed. RESULTS: A total of 629 patients were
      included in this study; 175 (28%) had cirrhosis. In an intention-to-treat
      analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis
      achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%,
      47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively.
      Discontinuation of therapy owing to adverse events was observed in 30 (17%)
      individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001).
      CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients
      with cirrhosis is lower than in those without cirrhosis, although this antiviral
      combination still leads to a substantial rate of SVR in those carrying HCV
      genotype 3. A higher rate of discontinuations of HCV therapy due to adverse
      events among cirrhotic patients could partially explain the differences in the
      SVR rate between both populations.

PMID- 22955436
TI  - Rate of transmission of extended-spectrum beta-lactamase-producing
      enterobacteriaceae without contact isolation.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      are emerging worldwide. Contact isolation is recommended; however, little is
      known about the rate of transmission without contact isolation in the non
      epidemic setting. Therefore, we aimed to estimate the rate of spread (R(0)) of
      ESBL-producing Enterobacteriaceae in a tertiary care center with 5 intensive care
      units. METHODS: In this observational cohort study performed from June 1999
      through April 2011, all patients at the University Hospital Basel, Switzerland,
      who were hospitalized in the same room as a patient colonized or infected with an
      ESBL-producing Enterobacteriaceae for at least 24 hours (index case) were
      screened for ESBL carriage by testing of rectal swab samples, swab samples from
      open wounds or drainages, and urine samples from patients with foley catheters.
      Strains with phenotypic evidence for ESBL were confirmed by polymerase chain
      reaction. Nosocomial transmission was assumed when the result of screening for
      ESBL carriage in a contact patient was positive and molecular typing by pulsed
      field gel electrophoresis (PFGE) revealed clonal relatedness with the strain from
      the index patient. RESULTS: Active screening for ESBL carriage could be performed
      in 133 consecutive contact patients. Transmission confirmed by PFGE occurred in 2
      (1.5%) of 133 contact patients, after a mean exposure to the index case of 4.3
      days. CONCLUSIONS: The estimated rate of spread of ESBL-producing
      Enterobacteriaceae-in particular, Escherichia coli-was low in a tertiary care
      university-affiliated hospital with high levels of standard hygiene precautions.
      The low level of nosocomial transmission and the rapid emergence of community
      acquired ESBL challenge the routine use of contact isolation in a non-epidemic
      setting, saving resources and potentially improving patient care.

PMID- 22955437
TI  - Serological response to treatment of syphilis according to disease stage and HIV
      status.
AB  - BACKGROUND: Serology is the mainstay for syphilis diagnosis and treatment
      monitoring. We investigated serological response to treatment of syphilis
      according to disease stage and HIV status. METHODS: A retrospective cohort study
      of 264 patients with syphilis was conducted, including 90 primary, 133 secondary,
      33 latent, and 8 tertiary syphilis cases. Response to treatment as measured by
      the Venereal Disease Research Laboratory (VDRL) test and a specific IgM
      (immunoglobulin M) capture enzyme-linked immunosorbent assay (ELISA; Pathozyme
      IgM) was assessed by Cox regression analysis. RESULTS: Forty-two percent of
      primary syphilis patients had a negative VDRL test at their diagnosis. Three
      months after treatment, 85%-100% of primary syphilis patients had reached the
      VDRL endpoint, compared with 76%-89% of patients with secondary syphilis and 44%
      79% with latent syphilis. In the overall multivariate Cox regression analysis,
      serological response to treatment was not influenced by human immunodeficiency
      virus (HIV) infection and reinfection. However, within primary syphilis, HIV
      patients with a CD4 count of <500 cells/MUL had a slower treatment response (P =
      .012). Compared with primary syphilis, secondary and latent syphilis showed a
      slower serological response of VDRL (P = .092 and P < .001) and Pathozyme-IgM
      tests (P < .001 and P = .012). CONCLUSIONS: The VDRL should not be recommended as
      a screening test owing to lack of sensitivity. The syphilis disease stage
      significantly influences treatment response whereas HIV coinfection only within
      primary syphilis has an impact. VDRL test titers should decline at least 4-fold
      within 3-6 months after therapy for primary or secondary syphilis, and within 12
      24 months for latent syphilis. IgM ELISA might be a supplement for diagnosis and
      treatment monitoring.

PMID- 22955438
TI  - Increasing incidence of hepatocellular carcinoma in HIV-infected patients in
      Spain.
AB  - BACKGROUND: To report the clinical and epidemiological characteristics of
      hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency
      virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients
      diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included.
      The main characteristics of HCC cases are described and comparisons between cases
      according to the year of diagnosis are presented. RESULTS: Eighty-two cases of
      HCC in HIV-infected patients were included, all of them related to viral
      hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus
      (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC
      was diagnosed, a progressive increment in the incidence of HCC in the cohort has
      occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence
      HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009.
      Death occurred in 65 patients (79%), with a median survival of 91 days
      (interquartile range, 31-227 days). Three of 11 patients (28%) who received
      potentially curative therapy died, compared with 62 of 71 patients (87%) who did
      not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed
      before 2005, cases diagnosed later did not show a higher survival rate.
      CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected
      patients. A sharp increase in its incidence has occurred in those also infected
      by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an
      advanced stage, and mortality continues to be very high, with no significant
      changes in recent years. Earlier diagnosis, which may allow potentially curative
      therapy, is necessary.

PMID- 22955440
TI  - Editorial commentary: control of multidrug-resistant microorganisms: beyond the
      hospital.

PMID- 22955439
TI  - Evaluation of the practice of antifungal prophylaxis use in patients with newly
      diagnosed acute myeloid leukemia: results from the SEIFEM 2010-B registry.
AB  - BACKGROUND: To analyze the efficacy of antifungal prophylaxis (AFP) with
      posaconazole and itraconazole in a real-life setting of patients with acute
      myeloid leukemia (AML) during the first induction of remission. METHODS: From
      January 2010 to June 2011, all patients with newly diagnosed AML were
      consecutively registered and prospectively monitored at 30 Italian hematological
      centers. Our analysis focused on adult patients who received intensive
      chemotherapy and a mold-active AFP for at least 5 days. To determine the efficacy
      of prophylaxis, invasive fungal disease (IFD) incidence, IFD-attributable
      mortality, and overall survival were evaluated. RESULTS: In total, 515 patients
      were included in the present analysis. Posaconazole was the most frequently
      prescribed drug (260 patients [50%]) followed by fluconazole (148 [29%]) and
      itraconazole (93 [18%]). When comparing the groups taking posaconazole and
      itraconazole, there were no significant differences in the baseline clinical
      characteristics, whereas there were significant differences in the percentage of
      breakthrough IFDs (18.9% with posaconazole and 38.7% with itraconazole, P< .001).
      The same trend was observed when only proven/probable mold infections were
      considered (posaconazole, 2.7% vs itraconazole, 10.7%, P= .02). There were no
      significant differences in the IFD-associated mortality rate, while posaconazole
      prophylaxis had a significant impact on overall survival at day 90 (P= .002).
      CONCLUSIONS: During the last years, the use of posaconazole prophylaxis in high
      risk patients has significantly increased. Although our study was not randomized,
      it demonstrates in a real-life setting that posaconazole prophylaxis confers an
      advantage in terms of both breakthrough IFDs and overall survival compared to
      itraconazole prophylaxis. CLINICAL TRIALS REGISTRATION: NCT01315925.

PMID- 22955441
TI  - Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening
      for intensified tuberculosis case finding in a South African HIV clinic.
AB  - BACKGROUND: Current symptom screening algorithms for intensified tuberculosis
      case finding or prior to isoniazid preventive therapy (IPT) in patients infected
      with human immunodeficiency virus (HIV) were derived from antiretroviral-naive
      cohorts. There is a need to validate screening algorithms in patients on
      antiretroviral therapy (ART). METHODS: We performed cross-sectional evaluation of
      the diagnostic accuracy of symptom screening, including the World Health
      Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected
      individuals pre-ART and on ART undergoing screening prior to IPT. RESULTS: A
      total of 1429 participants, 54% on ART, had symptom screening and a sputum
      culture result available. Culture-positive tuberculosis was diagnosed in 126
      patients (8.8%, 95% confidence interval [CI], 7.4%-10.4%). The WHO symptom screen
      in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs
      47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was
      independent of CD4(+) count in multivariable analyses. The posttest probability
      of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%-10.8%) and
      4.4% (95% CI, 3.7%-5.2%) for the pre-ART and on-ART groups, respectively.
      Addition of body mass index to the WHO screen significantly improved
      discriminatory ability in both ART groups, which was further improved by adding
      CD4 count and ART duration. CONCLUSIONS: The WHO symptom screen has poor
      sensitivity, especially among patients on ART, in a clinic where regular
      tuberculosis screening is practiced. Consequently, a significant proportion of
      individuals with tuberculosis would inadvertently be placed on isoniazid
      monotherapy despite high negative predictive values. Until more sensitive methods
      of ruling out tuberculosis are established, it would be prudent to do a sputum
      culture prior to IPT where this is feasible.

PMID- 22955442
TI  - High rate of New Delhi metallo-beta-lactamase 1-producing bacterial infection in
      China.

PMID- 22955443
TI  - Day zero ambulation under modified femoral nerve block after minimally invasive
      surgery for total knee arthroplasty: preliminary report.
AB  - Ambulation in the early postoperative period of total knee arthroplasty is
      crucial, in order to avoid complications and obtain preferable outcomes. Although
      a femoral nerve block can provide enough postoperative analgesia after total knee
      arthroplasty, falling, or other accidents due to motor paresis, are potentially
      adverse events in patients who have received a conventional femoral nerve block.
      We devised a modified femoral nerve block to spare voluntary knee extension
      ability, and clinically applied it to patients who received total knee
      arthroplasty under minimally invasive surgery. In our new-approach nerve blockade
      technique, the main targets of the sensory nerves are the saphenous nerves which
      branch out from the femoral nerve trunk. All the patients rated pain at bed rest
      between 0 and 3 on a numerical rating scale 3 h after the operation. In addition,
      the rectus femoris muscle was not affected at all, and the surgically invaded
      vastus medialis oblique muscle was completely anesthetized. Patients were able to
      not only actively raise their extremities with their knee in extension, but also
      to flex the knee in the air without pain or aggravation. On day 0, the patients
      were able to walk around, with the leg that had been operated upon not giving
      way. Our anesthetic approach can provide better pain relief than a conventional
      femoral nerve block, while the patients achieve ambulation on the day of the
      procedure, following minimally invasive knee surgery.

PMID- 22955444
TI  - Metal-free selenium doped carbon nanotube/graphene networks as a synergistically
      improved cathode catalyst for oxygen reduction reaction.
AB  - The ongoing search for new non-precious-metal catalysts (NPMCs) with excellent
      electrocatalytic performance to replace Pt-based catalysts has been viewed as an
      important strategy to promote the development of fuel cells. Recent studies have
      proven that carbon materials doped with atoms which have a relatively small
      atomic size (e.g. N, B, P or S), have also shown pronounced catalytic activity.
      Herein, we demonstrate the successful fabrication of CNT/graphene doped with Se
      atoms, which has a relatively large atomic size, by a simple, economical, and
      scalable approach. The electrocatalytic performance of the resulting Se-doped CNT
      graphene catalyst exhibits excellent catalytic activity, long-term stability, and
      a high methanol tolerance compared to commercial Pt/C catalysts. Our results
      confirmed that combining CNTs with graphene is an effective strategy to
      synergistically improve ORR activity. More importantly, it is also suggested that
      the development of graphite materials doped with Se or other heteroatoms of large
      size will open up a new route to obtain ideal NPMCs with realistic value for fuel
      cell applications.

PMID- 22955445
TI  - Relationship of adiponectin and leptin to coronary artery disease, classical
      cardiovascular risk factors and atherothrombotic biomarkers in the IARS cohort.
AB  - Adiponectin and leptin link metabolic disorders and coronary artery disease
      (CAD). We analysed their relationship with CAD, classical risk factors and
      biomarkers in 287 CAD patients (cases) and 477 unaffected family members
      (controls) selected from the Indian Atherosclerosis Research Study (IARS).
      Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity
      markers. Novel biomarkers were measured according to manufacturer
      recommendations. Adverse clinical events were recorded through telephonic follow
      up. Cases showed lower adiponectin levels (4684.62 +/- 190.73 ng/ml) than
      controls (5768.86 +/- 152.87 ng/ml) (p=1.58X10(-5)); Leptin levels were higher in
      affected males (12.47 +/- 1.32 ng/ml) than in male controls (9.53 +/- 1.19 ng/ml,
      p=0.017). Adiponectin 1st quartile showed significant protection against CAD in
      females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th
      (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher
      CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01,
      p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin
      levels. Adipokines showed opposing association trend with lipids, inflammatory
      and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity
      markers. Cases with recurrent event and controls who developed new cardiac event
      during follow up showed high adiponectin levels (p<0.05). A model that combined
      adiponectin, leptin and conventional risk factors yielded the best 'C' index
      (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed
      relatively poor survival curve as compared to the bottom Adiponectin tertile
      group. In conclusion, our findings strengthen the reported association between
      low adiponectin, high leptin, obesity-related metabolic disturbances and incident
      CAD in Asian Indians.

PMID- 22955446
TI  - CD38 signals upregulate expression and functions of matrix metalloproteinase-9 in
      chronic lymphocytic leukemia cells.

PMID- 22955447
TI  - Bioactivity of Dianthus caryophyllus, Lepidium sativum, Pimpinella anisum, and
      Illicium verum essential oils and their major components against the West Nile
      vector Culex pipiens.
AB  - Mosquitoes constitute a severe health problem in many areas all over the world.
      There are many regions of the tropics and subtropics where mosquitoes are one of
      the main reasons for inhibiting the economic upgrade. Except nuisance, their
      medical importance is another matter of attention since mosquitoes are vectors
      for a wide variety of vector-borne diseases. Due to disadvantages of currently
      used chemical control methods, it is unavoidable to search for eco-friendly new
      molecules. We report herein the evaluation of the larvicidal effect exhibited by
      essential oils of Dianthus caryophyllus, Lepidium sativum, Pimpinella anisum, and
      Illicium verum against late third to early fourth instar mosquito larvae of Culex
      pipiens. Furthermore, phytochemical analysis of plant samples revealed their
      major compounds to be beta-caryophyllene, eugenol, eucalyptol, alpha-terpinyl
      acetate, and (E)-anethole which were also tested for their potential larvicidal
      activity. For D. caryophyllus and L. sativum, this was the first report on the
      chemical composition of their essential oils. The essential oils of I. verum and
      P. anisum demonstrated high larvicidal activity with a LC(50) <18 mg L(-1). The
      other two essential oils of D. caryophyllus and L. sativum revealed moderate
      larvicidal activity, displaying a LC(50) value above 50 mg L(-1). Among the pure
      components, the most toxic were eugenol, (E)-anethole, and alpha-terpinyl
      acetate, with LC(50) values 18.28, 16.56, and 23.03 mg L(-1), respectively.
      Eucalyptol (1,8 cineole) and beta-caryophyllene were inactive at concentrations
      even as high as 100 mg L(-1), showing the least significant activity against
      mosquito larvae. Results allow some rationalization on the relative importance of
      the major compounds regarding the larvicidal activity of selected essential oils
      and their potential use as vector control agents.

PMID- 22955448
TI  - Fecal coliform population dynamics associated with the thermophilic stabilization
      of treated sewage sludge.
AB  - The inactivation of fecal coliforms in anaerobic batch reactors has been
      investigated at the thermophilic temperatures of 50, 55 and 60  degrees C.
      Throughout inactivation experiments at each temperature, individual colonies were
      isolated and identified by 16S rDNA gene sequencing to illustrate how the
      diversity of fecal coliforms is affected by thermophilic treatment. Results
      indicate that even though fecal coliforms in raw sewage sludge are comprised of
      several different bacterial species, each with variable temperature induced decay
      rates, the overall inactivation of fecal coliforms in raw sewage sludge was found
      to follow a first-order relationship. No tailing was observed across the range of
      fecal coliform concentrations measured. Fecal coliforms in raw sludge contained
      six different genera of bacteria and were 62% enriched in E. coli. Within 1.5 log
      removal of fecal coliform concentration by thermophilic treatment, the
      populations had shifted to, and remained at 100% E. coli. Subsequent inactivation
      rates measured in isolated fecal coliform strains confirmed that E. coli cells
      isolated post-treatment were more thermotolerant than E. coli and non-E coli
      bacteria isolated prior to thermal treatment. Overall, this study describes the
      potential enrichment of thermotolerant E. coli in biosolids fecal coliforms and
      demonstrates that while thermotolerant species are present at the end of
      treatment, pure first-order approximations are appropriate for estimating
      residence times to reduce fecal coliforms to levels promulgated in U.S. Class A
      biosolids standards.

PMID- 22955449
TI  - Femoral geometric parameters and BMD measurements by DXA in adult patients with
      different types of osteogenesis imperfecta.
AB  - OBJECTIVES: Osteogenesis imperfecta (OI) is an inherited disorder characterized
      by increased bone fragility with recurrent fractures that leads to skeletal
      deformities in severe cases. Consequently, in most OI patients, the hip is the
      only reliable measuring site for estimating future fracture risk. The aim of the
      study was to assess the applicability of hip structure analysis (HSA) by DXA in
      adult patients with osteogenesis imperfecta. MATERIALS AND METHODS: We evaluated
      bone mineral density (BMD) and hip structure analysis (HSA) by DXA, including
      cross-sectional area (CSA), cross-sectional moment of inertia (CSMI) and femoral
      strength index (FSI) in 30 adult patients with different types of OI and 30 age
      matched healthy controls (CO). The OI total group (OI-tot) was divided into two
      subgroups: the mild OI I group (OI-I) and the more severe OI III and IV group (OI
      III-IV). RESULTS: The mean neck BMD of OI-I and OI-III-IV were significantly
      lower compared to CO (-15.9 %, p < 0.005 and -37.5 %, p < 0.001 respectively).
      Similar results were observed at trochanter and total hip. CSA and the CSMI value
      were significantly lower for OI-I (-23.2 %, p < 0.001) and OI-III-IV (-45.9 %, p
      < 0.001) in comparison to CO. In addition, significant differences were found
      between the mild OI-I and the severe OI-III-IV group (-29.6 %, p < 0.05). FSI was
      significantly decreased in the OI-III-IV (25.7 %, p < 0.05) in comparison to the
      CO. Furthermore, significant correlations between BMD and HSA and between HSA and
      height and weight were found in osteogenesis imperfecta and controls. CONCLUSION:
      BMD measurement in osteogenesis imperfecta patients is very critical. The
      combination of BMD and geometric structural measurements at the hip in
      osteogenesis imperfecta patients may represent an additional helpful means in
      estimating bone strength and fracture risk.

PMID- 22955451
TI  - Hepatic haemangioma and conjugated hyperbilirubinemia.

PMID- 22955450
TI  - Oral microbial profile discriminates breast-fed from formula-fed infants.
AB  - OBJECTIVES: Little is known about the effect of diet on the oral microbiota of
      infants, although diet is known to affect the gut microbiota. The aims of the
      present study were to compare the oral microbiota in breast-fed and formula-fed
      infants, and investigate growth inhibition of streptococci by infant-isolated
      lactobacilli. METHODS: A total of 207 mothers consented to participation of their
      3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38
      (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva
      from all of their infants was cultured for Lactobacillus species, with isolate
      identifications from 21 infants. Lactobacillus isolates were tested for their
      ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73
      infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM)
      and by quantitative polymerase chain reaction for Lactobacillus gasseri. RESULTS:
      Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed
      infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected
      taxa, and total salivary lactobacilli counts differed by feeding method.
      Multivariate modelling of HOMIM-detected bacteria and possible confounders
      clustered samples from breast-fed infants separately from formula-fed infants.
      The microbiota of breast-fed infants differed based on vaginal or C-section
      delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of
      the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L
      vaginalis. CONCLUSIONS: The microbiota of the mouth differs between 3-month-old
      breast-fed and formula-fed infants. Possible mechanisms for microbial differences
      observed include species suppression by lactobacilli indigenous to breast milk.

PMID- 22955453
TI  - Advances in the chemical analysis and biological activities of chuanxiong.
AB  - Chuanxiong Rhizoma (Chuan-Xiong, CX), the dried rhizome of Ligusticum chuanxiong
      Hort. (Umbelliferae), is one of the most popular plant medicines in the World.
      Modern research indicates that organic acids, phthalides, alkaloids,
      polysaccharides, ceramides and cerebrosides are main components responsible for
      the bioactivities and properties of CX. Because of its complex constituents,
      multidisciplinary techniques are needed to validate the analytical methods that
      support CX's use worldwide. In the past two decades, rapid development of
      technology has advanced many aspects of CX research. The aim of this review is to
      illustrate the recent advances in the chemical analysis and biological activities
      of CX, and to highlight new applications and challenges. Emphasis is placed on
      recent trends and emerging techniques.

PMID- 22955452
TI  - Future possibilities in migraine genetics.
AB  - Migraine with and without aura (MA and MO, respectively) have a strong genetic
      basis. Different approaches using linkage-, candidate gene- and genome-wide
      association studies have been explored, yielding limited results. This may
      indicate that the genetic component in migraine is due to rare variants;
      capturing these will require more detailed sequencing in order to be discovered.
      Next-generation sequencing (NGS) techniques such as whole exome and whole genome
      sequencing have been successful in finding genes in especially monogenic
      disorders. As the molecular genetics research progresses, the technology will
      follow, rendering these approaches more applicable in the search for causative
      migraine genes in MO and MA. To date, no studies using NGS in migraine genetics
      have been published. In order to gain insight into the future possibilities of
      migraine genetics, we have looked at NGS studies in other diseases and have
      interviewed three experts in the field of genetics and complex traits. The
      experts' ideas suggest that the preferred NGS approach depends on the expected
      effect size and the frequency of the variants of interest. Family-specific
      variants can be found by sequencing a small number of individuals, while a large
      number of unrelated cases are needed to find common and rare variants. NGS is
      currently hampered by high cost and technical problems concurrent with analyzing
      large amounts of data generated, especially by whole genome sequencing. As genome
      wide association chips, exome sequencing and whole genome sequencing gradually
      become more affordable, these approaches will be used on a larger scale. This may
      reveal new risk variants in migraine which may offer previously unsuspected
      biological insights.

PMID- 22955454
TI  - Design, practical synthesis, and biological evaluation of novel 6
      (pyrazolylmethyl)-4-quinoline-3-carboxylic acid derivatives as HIV-1 integrase
      inhibitors.
AB  - A series of novel 6-(pyrazolylmethyl)-4-oxo-4-quinoline-3-carboxylic acid
      derivatives bearing different substituents on the N-position of quinoline ring
      were designed and synthesized as potential HIV-1 integrase (IN) inhibitors, based
      on the structurally related GS-9137 scaffold. The structures of all new compounds
      were confirmed by 1H-NMR, 13C-NMR and ESI (or HRMS) spectra. Detailed synthetic
      protocols and the anti-IN activity studies are also presented.

PMID- 22955455
TI  - Synthesis and protective effect of scutellarein on focal cerebral
      ischemia/reperfusion in rats.
AB  - Scutellarein, the main metabolite of scutellarin in vivo, has relatively better
      solubility, bioavailability and bio-activity than scutellarin. However, compared
      with scutellarin, it is very difficult to obtain scutellarein from Nature.
      Therefore, the present study focused on establishing an efficient route for the
      synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score
      and cerebral infarction volume with the administration of scutellarein were then
      used to compare its neuroprotective effects on focal cerebral
      ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO)
      with those of scutellarin. The results showed that scutellarein had better
      protective effect on focal cerebral ischemia/reperfusion than scutellarin, which
      laid the foundation for further research and development of scutellarein as a
      promising candidate for ischemic cerebro-vascular disease.

PMID- 22955456
TI  - Activity-guided isolation of antioxidant compounds from Rhizophora apiculata.
AB  - Rhizophora apiculata (R. apiculata) contains an abundance of biologically active
      compounds due its special salt-tolerant living surroundings. In this study, the
      total phenolic content and antioxidant activities of various extract and
      fractions of stem of R. apiculata were investigated. Results indicated that
      butanol fraction possesses the highest total phenolic content (181.84 mg/g GAE/g
      dry extract) with strongest antioxidant abilities. Following in vitro antioxidant
      activity-guided phytochemical separation procedures, lyoniresinol-3alpha-O-beta
      arabinopyranoside (1), lyoniresinol-3alpha-O-beta-rhamnoside (2), and afzelechin
      3-O-L-rhamno-pyranoside (3) were separated from the butanol fraction. These
      compounds showed more noticeable antioxidant activity than a BHT standard in the
      DPPH, ABTS and hydroxyl radical scavenging assays. HPLC analysis results showed
      that among different plant parts, the highest content of 1-3 was located in the
      bark (0.068%, 0.066% and 0.011%, respectively). The results imply that the R.
      apiculata might be a potential source of natural antioxidants and 1-3 are
      antioxidant ingredients in R. apiculata.

PMID- 22955457
TI  - Regiocontrolled microwave assisted bifunctionalization of 7,8-dihalogenated
      imidazo[1,2-a]pyridines: a one pot double-coupling approach.
AB  - The reactivity of the 7-chloro-8-iodo- and 8-chloro-7-iodoimidazo[1,2-a]pyridines
      1a-e diversely substituted on the 2 position, towards Suzuki-Miyaura,
      Sonogashira, and Buchwald-Hartwig cross-coupling reactions as well as cyanation
      was evaluated. Various methodologies are proposed to introduce aryl, heteroaryl,
      alkyne, amine or cyano groups in the two positions depending on the nature of the
      substituent present in position 2. In both series, the substitution of the iodine
      atom was totally regioselective and the difficulty was to substitute the chlorine
      atom in a second step. Until now, only hetero(aryl) groups could be introduced
      though Suzuki-Miyaura cross-coupling. We overcame this problem evaluating both
      regioisomers in parallel. The double coupling approach was also studied allowing
      the one pot Suzuki/Suzuki, cyanation/Sonogashira and cyanation/Buchwald reactions
      leading to polyfunctionnalized imidazo[1,2-a]pyridines.

PMID- 22955459
TI  - Burden of sepsis in children: perspectives from pediatric intensive care.

PMID- 22955460
TI  - Infants with human immunodeficiency virus exposure or infection in the pediatric
      intensive care unit.

PMID- 22955461
TI  - Should intravenous immunoglobulin be given to patients with postoperative
      chylothorax?.

PMID- 22955462
TI  - A new satisfaction tool: what do we do with it?

PMID- 22955463
TI  - "You're not Superman you know..." (1).

PMID- 22955464
TI  - Who is minding the store: intensive care unit personnel and its effect on cardiac
      arrest outcome.

PMID- 22955465
TI  - Updates to the Pediatric Advanced Life Support course: are we running just to
      stand still?

PMID- 22955466
TI  - Peripheral central catheter insertion: eyes or device?

PMID- 22955467
TI  - One is not zero.

PMID- 22955468
TI  - H1N1 in Japanese children - more data but even more questions.

PMID- 22955469
TI  - "My way or the highway" versus "Whatever the family wants" - intensivists reject
      both extremes.

PMID- 22955470
TI  - Thrombocytopenia and bleeding in the intensive care unit: what's in a number?

PMID- 22955471
TI  - Intensive care requirement, rather than degree of serum ferritin elevation,
      predicts mortality in macrophage activation syndrome.

PMID- 22955473
TI  - (H3N-BH3)4: the ammonia borane tetramer.
AB  - For this special edition of PCCP dealing with prediction of new molecules using
      quantum mechanical methods, we propose a structure for (H(3)N-BH(3))(4), the
      isolated ammonia borane tetramer in gas phase, for which there are no
      experimental reports. The structure, belonging to the S(4) point group, was found
      at the MP2/6-311++G(d,p) level of theory; the total energy was computed at the
      CCSD(T) level including BSSE correction, affording a binding energy of 40.1 kcal
      mol(-1). The tetramer is stabilized by a network of dihydrogen bonds. We study
      the stabilizing interactions via QTAIM, obtaining eight N-H(delta+)...(delta-)H-B
      bonding interactions characterized as hydrogen bonds by application of the Koch
      Popelier rules; in addition, two highly controversial B-H(delta-)...(delta-)H-B
      interactions are also predicted by a topological analysis of the electron
      density.

PMID- 22955474
TI  - Do members of the British public know how to contact emergency medical services
      when abroad?
AB  - There is increased demand for emergency healthcare by the public when abroad.
      This study aimed to investigate adults' reported level of knowledge about how to
      contact emergency healthcare services while abroad. A street survey was
      administered at various times, over several days, to 554 members of the general
      public who had been abroad in the previous 18 months. Only 33.6% [95% confidence
      interval (29.6%-37.7%)] of respondents reported that they knew the emergency
      medical number for the country last visited. This did not differ by sex (34.2%
      males vs. 33% females). Those fluent in the language of the country last visited
      were more likely to report knowing the emergency number for that country (54%),
      compared with those who were not (24.8%) (P<0.001). It is concerning that the
      majority of the general public do not appear to know how to contact emergency
      medical services while abroad. More targeted health education campaigns that
      address this are needed.

PMID- 22955475
TI  - Efforts to increase public awareness may result in more timely diagnosis of
      rheumatoid arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) in the United Arab Emirates
      (UAE) have previously been found to have a long delay to diagnosis and low
      utilization of disease-modifying antirheumatic drugs (DMARDs). Over the past 5
      years, support groups, awareness programs, and public campaigns have been
      instituted in the region. AIM: This study aimed to assess whether such
      initiatives have affected the lag to diagnosis previously observed. METHODS:
      Demographic, disease, and treatment data on the first 100 patients meeting
      American College of Rheumatology (1987) criteria for RA, presenting to our
      practice for the first time, were compared with similar data from 2006 on
      patients presenting to a different musculoskeletal clinic. RESULTS: Subjects had
      a mean age of 40.2 (+/-11.0) years (42.2 [+/-12.3] years in the previous study;
      Student t test, P > 0.05). Rheumatoid factor was positive in 62% of subjects,
      whereas 73% were titer positive in the previous study (chi(2) test, P > 0.05).
      There was a mean reduction in lag time from symptom onset to diagnosis by 45.8%,
      from 14.4 (+/-15.6) to 7.8 (+/-12.1) months (Student t test, P = 0.001) between
      data sets. The lag to initial DMARD was also reduced by a mean of 34.9%, from
      19.2 (+/-24) to 12.5 (+/-21.7) months (Student t test, P = 0.04). CONCLUSIONS:
      Findings suggest that the lag to diagnosis and initiation of DMARD therapy has
      reduced significantly among patients with RA in the United Arab Emirates, over
      the past 5 years. This may be attributed to the inception of patient support
      groups and increasing public awareness. Larger studies are needed to substantiate
      this further and to address whether shorter lag times can positively influence
      rates of disease remission and quality of life for our patients with RA (as this
      was a region specific study).

PMID- 22955476
TI  - Survival and extrapulmonary course of connective tissue disease after lung
      transplantation.
AB  - BACKGROUND: Connective tissue disease (CTD)-related lung dysfunction is a common
      cause of morbidity and mortality; however, few lung transplantations (LTs) are
      performed in this population secondary to uncertainty regarding the
      posttransplant survival, outcome, and management. OBJECTIVES: The objectives were
      to evaluate the survival and the pulmonary and extrapulmonary courses of CTD
      after LT. METHODS: Survival outcomes of patients documented within the Organ
      Procurement and Transplantation Network who had undergone a LT for CTD were
      compared with those who underwent LT for chronic obstructive pulmonary disease
      (COPD) and idiopathic pulmonary fibrosis (IPF). In addition, the pulmonary and
      extrapulmonary courses of the CTD were evaluated after LT. RESULTS: From 1991 to
      2009, there were 284 documented LT in patients with CTD. Post-LT cumulative
      survival of patients with CTD was less than that for COPD through 5 years, with a
      difference that peaked at 1 year (72.7% vs. 83.1%, P < 0.001). When patients with
      CTD were compared with those with IPF, a difference was only noted at 1 year
      (72.7% vs. 77.7%, P = 0.049). There were no documented post-LT pulmonary
      recurrences of the CTD, and extrapulmonary flares of the CTD were rare (1
      possible flare per 20.3 patient-years and 1 probable flare per 81.0 patient
      years). CONCLUSIONS: Cumulative survival of patients with CTD who underwent LT is
      similar to those with IPF and slightly less than those with COPD, with an
      increased risk of mortality that was most prominent at 6 months after transplant
      followed by subsequent narrowing of the survival differences over time. Lung
      transplantation may be a viable therapeutic option for patients with end-stage
      lung dysfunction resulting from a CTD.

PMID- 22955477
TI  - Relation of sensory peripheral neuropathy in Sjogren syndrome to anti-Ro/SSA.
AB  - BACKGROUND: Sjogren syndrome is a common, chronic autoimmune disease that
      typically produces inflammation and poor function of the salivary and lacrimal
      glands. Other organs can be affected, including the nervous system. Sensory
      peripheral neuropathy is a common manifestation of the disease. METHODS: Eight
      eight patients attending a dry eyes-dry mouth clinic were diagnosed to have
      primary Sjogren syndrome and underwent a neurological examination. Anti-Ro (or
      SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno
      Lia and BioPlex ANA screen. Serum vitamin B(12) levels were determined using an
      enzyme-linked microtiter plate assay. RESULTS: Twenty-seven (31%) of the 88
      patients had peripheral neuropathy as defined by loss of light touch,
      proprioception, or vibratory sensation. Anti-Ro and anti-La were found by
      immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (chi(2) = 8.46,
      P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and
      anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had
      neuropathy (chi(2) = 5.587, P = 0.018, compared to those without anti-Ro). There
      was no relationship of the other, more sensitive measures of anti-Ro and anti-La
      to neuropathy. In addition, we found no association of serum vitamin B(12) levels
      to neuropathy among these patients with Sjogren syndrome. CONCLUSIONS: Sensory
      peripheral neuropathy is common among patients with Sjogren syndrome and is
      associated with the presence of anti-Ro and anti-La when determined by
      immunodiffusion.

PMID- 22955478
TI  - Spanning generations-appointment reminder preferences among patients with
      rheumatic diseases.
AB  - OBJECTIVE: This study aimed to determine the appointment reminder preferences of
      patients presenting to rheumatology clinics. METHODS: An anonymous, self-directed
      survey was given to all patients attending our rheumatology clinic. Patients
      indicated age and reminder preferences in modality and timing. Patients were then
      divided into generational age groups as follows: generation Y (18-28 years),
      generation X (29-49 years), baby boomers (50-67 years), the silent generation (68
      85 years), and the GI generation (>=86 years). Overall preferences, as well as
      preferences by generational age groups, were determined. RESULTS: A total of 1000
      survey forms were distributed among the patients; 949 were collected for a
      response rate of 94.9%. Of these 949 survey forms, we analyzed 637 (67.1%) and
      excluded 312 (32.9%).Of all patients, 99.5% viewed appointment reminders
      favorably. Most (72%, n = 461) of the patients surveyed indicated that they would
      prefer the timing of their reminder to be 4 days or less before their clinic
      appointment; 16% (n = 100) preferred timing between 5 and 7 days; another 12% (n
      = 77) of the patients indicated that they would prefer 8 days or longer in
      advance. Overall, the most preferred reminder modality was a telephone call (52%,
      n = 333). The least preferred modality overall was short message service
      (SMS)/text messaging (4%, n = 27). The most popular option selected in generation
      Y was text/SMS reminders, and patients belonging to that generational age group
      were more likely than any other group to favor text/SMS reminders (P < 0.0001).
      CONCLUSIONS: Improved rheumatology clinic attendance would be beneficial given
      the need for disease assessment and medication monitoring. Most patients view
      appointment reminders favorably; however, no studies have assessed the modality
      and timing preferences of patients in a US rheumatology clinic. Modality, but not
      timing, preferences vary with generational age. The preference for newer
      modalities such as text/SMS reminder was predominately observed in the patients
      of generation Y, a population prone to clinic nonattendance.

PMID- 22955479
TI  - Dermatomyositis: a rare presentation of HIV seroconversion illness.
AB  - Dermatomyositis is a rare autoimmune inflammatory myopathy with proximal muscle
      weakness and skin affection. Only 4 cases of HIV that subsequently developed
      dermatomyositis have been reported. This is the first case of dermatomyositis
      being the initial presentation of an acute seroconversion illness. We highlight
      the pathophysiology of dermatomyositis in HIV infection along with the complex
      issues of treatment in such cases. We report a case of a 50-year-old woman who
      presented with a 2 months' history of proximal muscle weakness with classic signs
      of dermatomyositis and consistent electromyographic and muscle biopsy. HIV (by
      enzyme-linked immunosorbent assay) was initially nonreactive, indeterminate at 4
      weeks, and positive at 8 weeks. It was further confirmed by Western blot and
      polymerase chain reaction. She was treated with prednisolone and antiretroviral
      therapy. A high degree of suspicion is required to diagnose HIV seroconversion
      when an individual presents with dermatomyositis. A fine balance of
      immunosuppressants and antiretroviral therapy needs to be maintained in the
      treatment of such cases.

PMID- 22955480
TI  - Etanercept therapy for psoriatic arthritis in the presence of recurrent non
      Hodgkin lymphoma.
AB  - Tumor necrosis factor inhibitors (TNFi) have established efficacy in psoriasis
      and psoriatic arthritis; however, there are concerns regarding the risk of
      lymphoma with their use. Although current data suggest that this risk is not
      increased with TNFi treatment, there are no data on the risk of recurrence of
      previously treated lymphoma under TNFi therapy. Herein, we describe a 46-year-old
      man with recurrent non-Hodgkin lymphoma whose refractory psoriatic arthritis was
      effectively treated for 5.5 years with the TNFi etanercept, initiated just 7
      months after achieving lymphoma remission, without recurrence of non-Hodgkin
      lymphoma. However, he subsequently died 6.5 years later of pancreatic
      adenocarcinoma.

PMID- 22955481
TI  - Recurrent cardiac tamponade in a child with newly diagnosed systemic-onset
      juvenile idiopathic arthritis.
AB  - A previously healthy 5-year-old boy presented with prolonged fever, evanescent
      rash, and arthralgias. Diagnostic tests were significant for marked systemic
      inflammation. He rapidly developed pleural and pericardial effusions with cardiac
      tamponade, requiring placement of a pericardial drain. He briefly responded to
      nonsteroidal anti-inflammatory drugs and pulse methylprednisolone, but tamponade
      recurred shortly thereafter. Subsequently, he required high-dose intravenous
      immunoglobulin, infliximab, and anakinra. Thus, we report a patient with severe
      serositis and recurrent cardiac tamponade as the initial presentation of systemic
      juvenile idiopathic arthritis (sJIA) and review the literature regarding
      pericarditis and tamponade in sJIA. This potentially fatal complication of sJIA
      requires timely recognition and therapy to avoid significant morbidity and
      mortality.

PMID- 22955482
TI  - Crohn ankylosis: a destructive elbow and wrist joint arthritis 2 decades
      following childhood abdominal pain.

PMID- 22955484
TI  - Basic science for the clinician 58: IgG subclasses.
AB  - In evolutionary terms, IgG is the most recent addition to the human humoral
      immune response, the most recent of the 5 isotypes (classes). The IgG 4
      subclasses and their multiple receptors, each with a unique structure and
      functions, speak to their broad repertoire of often overlapping functions. The
      IgG subclasses differ only slightly in structure, but therein lies their unique
      qualities. Focusing solely on the clinical niches filled by each and the clinical
      correlations thereof allows one to clearly see nature in its abhorrence of, and
      skill in filling, vacuums. One of the IgG subclasses, IgG4, the least in serum
      concentration, has recently become the topic of intense interest, as the linkage
      of certain diseases with IgG4 becomes apparent. As this association is studied,
      the molecular biology at the root of these diseases becomes the predominant
      cytokines explaining the pattern of histopathology.

PMID- 22955483
TI  - Acute infection of total knee arthroplasty due to a cat scratch in a patient with
      rheumatoid arthritis.

PMID- 22955485
TI  - Intestinal obstruction as the initial presentation of lupus mesenteric
      vasculitis.

PMID- 22955486
TI  - Hand angiography in connective tissue disease.

PMID- 22955488
TI  - Candida albicans infection of a reverse-polarity shoulder replacement in a
      patient with rheumatoid arthritis treated with etanercept.

PMID- 22955489
TI  - Intestinal tuberculosis mimicking Crohn disease in infliximab-treated rheumatoid
      arthritis.

PMID- 22955491
TI  - Nesfatin-1 as a novel cardiac peptide: identification, functional
      characterization, and protection against ischemia/reperfusion injury.
AB  - Nesfatin-1 is an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide. It
      controls feeding behavior, water intake, and glucose homeostasis. If
      intracerebrally administered, it induces hypertension, thus suggesting a role in
      central cardiovascular control. However, it is not known whether it is able to
      directly control heart performance. We aimed to verify the hypothesis that, as in
      the case of other hypothalamic satiety peptides, Nesfatin-1 acts as a peripheral
      cardiac modulator. By western blotting and QT-PCR, we identified the presence of
      both Nesfatin-1 protein and NUCB2 mRNA in rat cardiac extracts. On isolated and
      Langendorff-perfused rat heart preparations, we found that exogenous Nesfatin-1
      depresses contractility and relaxation without affecting coronary motility. These
      effects did not involve Nitric oxide, but recruited the particulate guanylate
      cyclase (pGC) known as natriuretic peptide receptor A (NPR-A), protein kinase G
      (PKG) and extracellular signal-regulated kinases1/2 (ERK1/2). Co
      immunoprecipitation and bioinformatic analyses supported an interaction between
      Nesfatin-1 and NPR-A. Lastly, we preliminarily observed, through post
      conditioning experiments, that Nesfatin-1 protects against ischemia/reperfusion
      (I/R) injury by reducing infarct size, lactate dehydrogenase release, and
      postischemic contracture. This protection involves multiple prosurvival kinases
      such as PKCepsilon, ERK1/2, signal transducer and activator of transcription 3,
      and mitochondrial K(ATP) channels. It also ameliorates contractility recovery.
      Our data indicate that: (1) the heart expresses Nesfatin-1, (2) Nesfatin-1
      directly affects myocardial performance, possibly involving pGC-linked NPR-A, the
      pGC/PKG pathway, and ERK1/2, (3) the peptide protects the heart against I/R
      injury. Results pave the way to include Nesfatin-1 in the neuroendocrine
      modulators of the cardiac function, also encouraging the clarification of its
      clinical potential in the presence of nutrition-dependent physio-pathologic
      cardiovascular diseases.

PMID- 22955493
TI  - Interpersonal psychotherapy (IPT) in major depressive disorder.
AB  - In this article, we will introduce interpersonal psychotherapy as an effective
      short-term treatment strategy in major depression. In IPT, a reciprocal
      relationship between interpersonal problems and depressive symptoms is regarded
      as important in the onset and as a maintaining factor of depressive disorders.
      Therefore, interpersonal problems are the main therapeutic targets of this
      approach. Four interpersonal problem areas are defined, which include
      interpersonal role disputes, role transitions, complicated bereavement, and
      interpersonal deficits. Patients are helped to break the interactions between
      depressive symptoms and their individual interpersonal difficulties. The goals
      are to achieve a reduction in depressive symptoms and an improvement in
      interpersonal functioning through improved communication, expression of affect,
      and proactive engagement with the current interpersonal network. The efficacy of
      this focused and structured psychotherapy in the treatment of acute unipolar
      major depressive disorder is summarized. This article outlines the background of
      interpersonal psychotherapy, the process of therapy, efficacy, and the expansion
      of the evidence base to different subgroups of depressed patients.

PMID- 22955492
TI  - Social prophylaxis through distant corpse removal in ants.
AB  - Living in groups raises important issues concerning waste management and related
      sanitary risks. Social insects such as ants live at high densities with
      genetically related individuals within confined and humid nests, all these
      factors being highly favorable for the spread of pathogens. Therefore, in
      addition to individual immunity, a social prophylaxis takes place, namely, by the
      removal of risky items such as corpses and their rejection at a distance from the
      ant nest. In this study, we investigate how Myrmica rubra workers manage to
      reduce encounters between potentially hazardous corpses and nestmates. Using both
      field and laboratory experiments, we describe how the spatial distribution and
      the removal distance of waste items vary as a function of their associated
      sanitary risks (inert item vs. corpse). In the field, corpse-carrying ants walked
      in a rather linear way away from the nest entrance and had an equal probability
      of choosing any direction. Therefore, they did not aggregate corpses in dedicated
      areas but scattered them in the environment. In both field and laboratory
      experiments, ants carrying corpses dropped their load in more remote-and less
      frequented-areas than workers carrying inert items. However, for equidistant
      areas, ants did not avoid dropping corpses at a location where they perceived
      area marking as a cue of high occupancy level by nestmates. Our results suggest
      that ants use distance to the nest rather than other occupancy cues to limit
      sanitary risks associated with dead nestmates.

PMID- 22955494
TI  - On our own behalf: a new editorial board and focus of EAPCN.

PMID- 22955490
TI  - Regulation of the cardiac sodium pump.
AB  - In cardiac muscle, the sarcolemmal sodium/potassium ATPase is the principal
      quantitative means of active transport at the myocyte cell surface, and its
      activity is essential for maintaining the trans-sarcolemmal sodium gradient that
      drives ion exchange and transport processes that are critical for cardiac
      function. The 72-residue phosphoprotein phospholemman regulates the sodium pump
      in the heart: unphosphorylated phospholemman inhibits the pump, and phospholemman
      phosphorylation increases pump activity. Phospholemman is subject to a remarkable
      plethora of post-translational modifications for such a small protein: the
      combination of three phosphorylation sites, two palmitoylation sites, and one
      glutathionylation site means that phospholemman integrates multiple signaling
      events to control the cardiac sodium pump. Since misregulation of cytosolic
      sodium contributes to contractile and metabolic dysfunction during cardiac
      failure, a complete understanding of the mechanisms that control the cardiac
      sodium pump is vital. This review explores our current understanding of these
      mechanisms.

PMID- 22955495
TI  - Harmonization process for the identification of medical events in eight European
      healthcare databases: the experience from the EU-ADR project.
AB  - OBJECTIVE: Data from electronic healthcare records (EHR) can be used to monitor
      drug safety, but in order to compare and pool data from different EHR databases,
      the extraction of potential adverse events must be harmonized. In this paper, we
      describe the procedure used for harmonizing the extraction from eight European
      EHR databases of five events of interest deemed to be important in
      pharmacovigilance: acute myocardial infarction (AMI); acute renal failure (ARF);
      anaphylactic shock (AS); bullous eruption (BE); and rhabdomyolysis (RHABD).
      DESIGN: The participating databases comprise general practitioners' medical
      records and claims for hospitalization and other healthcare services. Clinical
      information is collected using four different disease terminologies and free text
      in two different languages. The Unified Medical Language System was used to
      identify concepts and corresponding codes in each terminology. A common database
      model was used to share and pool data and verify the semantic basis of the event
      extraction queries. Feedback from the database holders was obtained at various
      stages to refine the extraction queries. MEASUREMENTS: Standardized and age
      specific incidence rates (IRs) were calculated to facilitate benchmarking and
      harmonization of event data extraction across the databases. This was an
      iterative process. RESULTS: The study population comprised overall 19 647 445
      individuals with a follow-up of 59 929 690 person-years (PYs). Age adjusted IRs
      for the five events of interest across the databases were as follows: (1) AMI: 60
      148/100 000 PYs; (2) ARF: 3-49/100 000 PYs; (3) AS: 2-12/100 000 PYs; (4) BE: 2
      17/100 000 PYs; and (5) RHABD: 0.1-8/100 000 PYs. CONCLUSIONS: The iterative
      harmonization process enabled a more homogeneous identification of events across
      differently structured databases using different coding based algorithms. This
      workflow can facilitate transparent and reproducible event extractions and
      understanding of differences between databases.

PMID- 22955496
TI  - Next-generation phenotyping of electronic health records.
AB  - The national adoption of electronic health records (EHR) promises to make an
      unprecedented amount of data available for clinical research, but the data are
      complex, inaccurate, and frequently missing, and the record reflects complex
      processes aside from the patient's physiological state. We believe that the path
      forward requires studying the EHR as an object of interest in itself, and that
      new models, learning from data, and collaboration will lead to efficient use of
      the valuable information currently locked in health records.

PMID- 22955497
TI  - Security practices and regulatory compliance in the healthcare industry.
AB  - OBJECTIVE: Securing protected health information is a critical responsibility of
      every healthcare organization. We explore information security practices and
      identify practice patterns that are associated with improved regulatory
      compliance. DESIGN: We employed Ward's cluster analysis using minimum variance
      based on the adoption of security practices. Variance between organizations was
      measured using dichotomous data indicating the presence or absence of each
      security practice. Using t tests, we identified the relationships between the
      clusters of security practices and their regulatory compliance. MEASUREMENT: We
      utilized the results from the Kroll/Healthcare Information and Management Systems
      Society telephone-based survey of 250 US healthcare organizations including
      adoption status of security practices, breach incidents, and perceived compliance
      levels on Health Information Technology for Economic and Clinical Health, Health
      Insurance Portability and Accountability Act, Red Flags rules, Centers for
      Medicare and Medicaid Services, and state laws governing patient information
      security. RESULTS: Our analysis identified three clusters (which we call leaders,
      followers, and laggers) based on the variance of security practice patterns. The
      clusters have significant differences among non-technical practices rather than
      technical practices, and the highest level of compliance was associated with
      hospitals that employed a balanced approach between technical and non-technical
      practices (or between one-off and cultural practices). CONCLUSIONS: Hospitals in
      the highest level of compliance were significantly managing third parties'
      breaches and training. Audit practices were important to those who scored in the
      middle of the pack on compliance. Our results provide security practice
      benchmarks for healthcare administrators and can help policy makers in developing
      strategic and practical guidelines for practice adoption.

PMID- 22955498
TI  - Insight into the ultrastructural organisation of sporulated oocysts of Eimeria
      nieschulzi (Coccidia, Apicomplexa).
AB  - Sporulated oocysts of Eimeria contain four sporocysts with two sporozoites each
      and a sporocyst residuum. The developing sporozoites are protected by the
      sporocyst wall and the robust double-layered oocyst wall. Because of problems
      with conventional fixatives, high-pressure freezing, followed by freeze
      substitution was used to achieve optimal ultrastructural preservation of oocysts,
      sporocysts and sporozoites. After embedding in Epon(r), ultrathin sections were
      examined by electron microscopy to select specific oocyst regions for further
      investigation by electron tomography (ET). ET allows high-resolution three
      dimensional views of subcellular structures within the oocysts and sporocysts.
      Analysis of several 300 nm sections by ET revealed a network of small tubular
      structures with a diameter of 70-120 nm inside the sporocysts which is decribed
      here for the first time. This network connects the residual body in a sporocyst
      with the endoplasmic reticulum (ER) of the surrounding sporozoites. The network
      consists of membrane-bound tubules that contain vesicles but no larger organelles
      like mitochondria. These tubules, named "sporocord", may have a function similar
      to an "umbilical cord" providing the sporozoites with metabolites for long-term
      survival. Small vesicular structures inside the ER of the sporozoites,
      multivesicular structures inside the residual bodies and vesicles in the tubules
      support this hypothesis.

PMID- 22955499
TI  - The immune response induced by DNA vaccine expressing nfa1 gene against Naegleria
      fowleri.
AB  - The pathogenic free-living amoeba, Naegleria fowleri, causes fatal primary
      amoebic meningoencephalitis in experimental animals and in humans. The nfa1 gene
      that was cloned from N. fowleri is located on pseudopodia, especially amoebic
      food cups and plays an important role in the pathogenesis of N. fowleri. In this
      study, we constructed and characterized retroviral vector and lentiviral vector
      systems for nfa1 DNA vaccination in mice. We constructed the retroviral vector
      (pQCXIN) and the lentiviral vector (pCDH) cloned with the egfp-nfa1 gene. The
      expression of nfa1 gene in Chinese hamster ovary cell and human primary nasal
      epithelial cell transfected with the pQCXIN/egfp-nfa1 vector or pCDH/egfp-nfa1
      vector was observed by fluorescent microscopy and Western blotting analysis. Our
      viral vector systems effectively delivered the nfa1 gene to the target cells and
      expressed the Nfa1 protein within the target cells. To evaluate immune responses
      of nfa1-vaccinated mice, BALB/c mice were intranasally vaccinated with viral
      particles of each retro- or lentiviral vector expressing nfa1 gene. DNA
      vaccination using viral vectors expressing nfa1 significantly stimulated the
      production of Nfa1-specific IgG subclass, as well as IgG levels. In particular,
      both levels of IgG2a (Th1) and IgG1 (Th2) were significantly increased in mice
      vaccinated with viral vectors. These results show the nfa1-vaccination induce
      efficiently Th1 type, as well as Th2 type immune responses. This is the first
      report to construct viral vector systems and to evaluate immune responses as DNA
      vaccination in N. fowleri infection. Furthermore, these results suggest that nfal
      vaccination may be an effective method for treatment of N. fowleri infection.

PMID- 22955500
TI  - Morphological and genetic characterization of Hysterothylacium zhoushanensis sp.
      nov. (Ascaridida: Anisakidae) from the flatfish Pseudorhombus oligodon (Bleeker)
      (Pleuronectiformes: Paralichthyidae) in the East China Sea.
AB  - Hysterothylacium zhoushanensis sp. nov. collected from the intestine of the
      flatfish Pseudorhombus oligodon (Bleeker) (Pleuronectiformes: Paralichthyidae) in
      the East China Sea is described and illustrated by light and scanning electron
      microscopy. The new species can be easily distinguished from its congeners by the
      presence of remarkable lateral alae, the very short intestinal caecum, the
      unusually long ventricular appendix (ratio of intestinal caecum to ventricular
      appendix 1:8.74-23.8), the short spicules (0.58-0.81 mm long, representing 1.70
      2.08 % of body length) and the number and arrangement of male caudal papillae (35
      42 pairs in total, arranged as 26-32 pairs of precloacal, two pairs of
      paracloacal and six to eight pairs of postcloacal). In addition, the adults and
      the putative third-stage larvae identified morphologically of the new species are
      characterised by sequencing and analysing the internal transcribed spacer (ITS)
      of the ribosomal DNA. The result reveals that they are homogeneous genetically,
      and all belong to the same species. Molecular analysis by comparing the ITS gene
      of H. zhoushanensis sp. nov. with these species of Hysterothylacium available in
      GenBank also seem to support the validity of the new species based on the
      morphological observation.

PMID- 22955501
TI  - Housefly (Musca domestica L.) control potential of Cymbopogon citratus Stapf.
      (Poales: Poaceae) essential oil and monoterpenes (citral and 1,8-cineole).
AB  - In spite of being a major vector for several domestic, medical, and veterinary
      pests, the control aspect of the common housefly, Musca domestica L. (Diptera:
      Muscidae) is often neglected. In the present study, the essential oil of
      Cymbopogon citratus and its major components were evaluated for control of
      housefly. The chemical composition analysis of C. citratus oil by gas
      chromatographic mass spectrometry (GC-MS) revealed citral (47 %) and 1,8-cineole
      (7.5 %) as principal components. The analysis of oil vapor by solid phase
      microextraction (SPME/GC-MS) showed increase in citral (74.9 %) and 1,8-cineole
      (8.6 %) content. Assay of oil against housefly larvae and pupae through contact
      toxicity assay showed lethal concentration (LC)(50) value of 0.41 MUl/cm(2) and
      of percentage inhibition rate (PIR) of 77.3 %, respectively. Fumigation assay was
      comparatively more effective with LC(50) of 48.6 MUl/L against housefly larvae,
      and a PIR value of 100 % against housefly pupae. The monoterpenes, citral, and
      1,8-cineole, when assessed for their insecticidal activity against housefly
      larvae, showed LC(50) of 0.002 and 0.01 MUl/cm(2) (contact toxicity assay) and
      LC(50) of 3.3 and 2.4 MUl/L (fumigation assay). For pupicidal assay, both citral
      and 1,8-cineole had a PIR value of 100 %. High efficacy of citral and 1,8-cineole
      against housefly, established them to be an active insecticidal agent of C.
      citratus oil. The study demonstrates potentiality of C. citratus oil as an
      excellent insecticide for housefly control, and the results open up the
      opportunity of oil/monoterpenes being developed into an eco-friendly, economical,
      and acceptable product.

PMID- 22955502
TI  - Absence of Borrelia spp., Candidatus Neoehrlichia mikurensis, and Anaplasma
      phagocytophilum in questing adult Dermacentor reticulatus ticks.
AB  - To determine whether Dermacentor reticulatus ticks are infected by Borrelia spp.,
      Candidatus Neoehrlichia mikurensis, or Anaplasma phagocytophilum, we collected
      questing adults in the outskirts of Berlin, Germany, examined them for the
      presence of DNA of these pathogens, and compared the infection rates to those of
      sympatric Ixodes ricinus ticks. Questing D. reticulatus adults appeared not to
      harbor the bacterial pathogens that are prevalent in I. ricinus ticks. Based on
      our sample size, the estimated prevalence of each of these pathogens in D.
      reticulatus ticks would be well below three tenth of a percent (<0.3 %). For
      pathogens which so rarely infect D. reticulatus ticks, this tick likely plays no
      epidemiologic vector role for either their enzootic transmission cycle in nature
      or their transmission to people.

PMID- 22955503
TI  - Volatility and aging of atmospheric organic aerosol.
AB  - Organic-aerosol phase partitioning (volatility) and oxidative aging are
      inextricably linked in the atmosphere because partitioning largely controls the
      rates and mechanisms of aging reactions as well as the actual amount of organic
      aerosol. Here we discuss those linkages, describing the basic theory of
      partitioning thermodynamics as well as the dynamics that may limit the approach
      to equilibrium under some conditions. We then discuss oxidative aging in three
      forms: homogeneous gas-phase oxidation, heterogeneous oxidation via uptake of gas
      phase oxidants, and aqueous-phase oxidation. We present general scaling arguments
      to constrain the relative importance of these processes in the atmosphere,
      compared to each other and compared to the characteristic residence time of
      particles in the atmosphere. 

PMID- 22955504
TI  - Hsp90: structure and function.
AB  - Hsp90 is a highly abundant and ubiquitous molecular chaperone which plays an
      essential role in many cellular processes including cell cycle control, cell
      survival, hormone and other signalling pathways. It is important for the cell's
      response to stress and is a key player in maintaining cellular homeostasis. In
      the last ten years, it has become a major therapeutic target for cancer, and
      there has also been increasing interest in it as a therapeutic target in
      neurodegenerative disorders, and in the development of anti-virals and anti
      protozoan infections. The focus of this review is the structural and mechanistic
      studies which have been performed in order to understand how this important
      chaperone acts on a wide variety of different proteins (its client proteins) and
      cellular processes. As with many of the other classes of molecular chaperone,
      Hsp90 has a critical ATPase activity, and ATP binding and hydrolysis known to
      modulate the conformational dynamics of the protein. It also uses a host of
      cochaperones which not only regulate the ATPase activity and conformational
      dynamics but which also mediate interactions with Hsp90 client proteins. The
      system is also regulated by post-translational modifications including
      phosphorylation and acetylation. This review discusses all these aspects of Hsp90
      structure and function.

PMID- 22955505
TI  - The solid-state photo-CIDNP effect and its analytical application : photo-CIDNP
      MAS NMR to study radical pairs.
AB  - Photochemically induced dynamic nuclear polarization (photo-CIDNP) is an effect
      that produces non-Boltzmann nuclear spin polarization which can be observed as
      modification of signal intensity in NMR spectroscopy. The effect is well known in
      liquid-state NMR where it is explained most generally by the classical radical
      pair mechanism (RPM). In the solid-state, other mechanisms are operative in the
      spin-dynamics of radical pairs such as three-spin mixing (TSM) and differential
      decay (DD). Initially the solid-state photo-CIDNP effect has been solely observed
      on natural photosynthetic reaction centers (RCs). Therefore the analytical
      capacity of the method has been explored in experiments on reaction centers (RCs)
      of the purple bacterium of Rhodobacter (R.) sphaeroides. Here we will provide an
      account on phenomenology, theory, and analytical capacity of the solid-state
      photo-CIDNP effect. 

PMID- 22955506
TI  - Three-dimensional aromatic networks.
AB  - Three-dimensional (3D) networks consisting of aromatic units and linkers are
      reviewed from various aspects. To understand principles for the construction of
      such compounds, we generalize the roles of building units, the synthetic
      approaches, and the classification of networks. As fundamental compounds,
      cyclophanes with large aromatic units and aromatic macrocycles with linear
      acetylene linkers are highlighted in terms of transannular interactions between
      aromatic units, conformational preference, and resolution of chiral derivatives.
      Polycyclic cage compounds are constructed from building units by linkages via
      covalent bonds, metal-coordination bonds, or hydrogen bonds. Large cage networks
      often include a wide range of guest species in their cavity to afford novel
      inclusion compounds. Topological isomers consisting of two or more macrocycles
      are formed by cyclization of preorganized species. Some complicated topological
      networks are constructed by self-assembly of simple building units. 

PMID- 22955507
TI  - New insights into the tropospheric oxidation of isoprene: combining field
      measurements, laboratory studies, chemical modelling and quantum theory.
AB  - In this chapter we discuss some of the recent work directed at further
      understanding the chemistry of our atmosphere in regions of low NO x , such as
      forests, where there are considerable emissions of biogenic volatile organic
      compounds, for example reactive hydrocarbons such as isoprene. Recent field
      measurements have revealed some surprising results, for example that OH
      concentrations are measured to be considerably higher than can be understood
      using current chemical mechanisms. It has also not proven possible to reconcile
      field measurements of other species, such as oxygenated VOCs, or emission fluxes
      of isoprene, using current mechanisms. Several complementary approaches have been
      brought to bear on formulating a solution to this problem, namely field studies
      using state-of-the-art instrumentation, chamber studies to isolate sub-sections
      of the chemistry, laboratory studies to measure rate coefficients, product
      branching ratios and photochemical yields, the development of ever more detailed
      chemical mechanisms, and high quality ab initio quantum theory to calculate the
      energy landscape for relevant reactions and to enable the rates of formation of
      products and intermediates for previously unknown and unstudied reactions to be
      predicted. The last few years have seen significant activity in this area, with
      several contrasting postulates put forward to explain the experimental findings,
      and here we attempt to synthesise the evidence and ideas. 

PMID- 22955508
TI  - Cancer chemoprevention and nutriepigenetics: state of the art and future
      challenges.
AB  - The term "epigenetics" refers to modifications in gene expression caused by
      heritable, but potentially reversible, changes in DNA methylation and chromatin
      structure. Epigenetic alterations have been identified as promising new targets
      for cancer prevention strategies as they occur early during carcinogenesis and
      represent potentially initiating events for cancer development. Over the past few
      years, nutriepigenetics - the influence of dietary components on mechanisms
      influencing the epigenome - has emerged as an exciting new field in current
      epigenetic research. During carcinogenesis, major cellular functions and
      pathways, including drug metabolism, cell cycle regulation, potential to repair
      DNA damage or to induce apoptosis, response to inflammatory stimuli, cell
      signalling, and cell growth control and differentiation become deregulated.
      Recent evidence now indicates that epigenetic alterations contribute to these
      cellular defects, for example epigenetic silencing of detoxifying enzymes, tumor
      suppressor genes, cell cycle regulators, apoptosis-inducing and DNA repair genes,
      nuclear receptors, signal transducers and transcription factors by promoter
      methylation, and modifications of histones and non-histone proteins such as p53,
      NF-kappaB, and the chaperone HSP90 by acetylation or methylation.The present
      review will summarize the potential of natural chemopreventive agents to
      counteract these cancer-related epigenetic alterations by influencing the
      activity or expression of DNA methyltransferases and histone modifying enzymes.
      Chemopreventive agents that target the epigenome include micronutrients (folate,
      retinoic acid, and selenium compounds), butyrate, polyphenols from green tea,
      apples, coffee, black raspberries, and other dietary sources, genistein and soy
      isoflavones, curcumin, resveratrol, dihydrocoumarin, nordihydroguaiaretic acid
      (NDGA), lycopene, anacardic acid, garcinol, constituents of Allium species and
      cruciferous vegetables, including indol-3-carbinol (I3C), diindolylmethane (DIM),
      sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate
      (PHI), diallyldisulfide (DADS) and its metabolite allyl mercaptan (AM), cambinol,
      and relatively unexplored modulators of histone lysine methylation (chaetocin,
      polyamine analogs). So far, data are still mainly derived from in vitro
      investigations, and results of animal models or human intervention studies are
      limited that demonstrate the functional relevance of epigenetic mechanisms for
      health promoting or cancer preventive efficacy of natural products. Also, most
      studies have focused on single candidate genes or mechanisms. With the emergence
      of novel technologies such as next-generation sequencing, future research has the
      potential to explore nutriepigenomics at a genome-wide level to understand better
      the importance of epigenetic mechanisms for gene regulation in cancer
      chemoprevention.

PMID- 22955509
TI  - Twisted arenes.
AB  - The nonbonded steric interactions of substituents at the crowded C4 and C5
      positions of phenanthrene cause the aromatic system to twist out of planarity.
      Similarly, the presence of substituents at the C1 and C12 positions of
      benzo[c]phenanthrene and at the C1 and C14 positions of dibenzo[c,g]phenanthrene
      are responsible for the helical twists of the aromatic frameworks. Highly
      substituted acenes, such as octamethylnaphthalene and decaphenylanthracene, also
      exhibit substantial end-to-end twists. The X-ray structures of these compounds
      allow direct measurements of the extent of the structural distortions. The
      configurational stabilities of many twisted arenes have also been determined. 

PMID- 22955510
TI  - Stochastic mirror symmetry breaking: theoretical models and simulation of
      experiments.
AB  - This chapter provides a review of recently elaborated mathematical models for
      explaining the salient features of two experimental studies selected for their
      relevance to the problem of stochastic mirror symmetry breaking and
      amplification. The first experiment modeled treats the phenomena of mirror
      symmetry breaking via the autocatalytic crystallization of the glycine and alpha
      amino acid system at the air-water interface. The second experiment deals with
      the lattice-controlled generation of homochiral oligopeptides, which we model
      based on a kinetic scheme for copolymerization in a closed reaction system. Since
      the fundamental paradigm of mutual inhibition lies at the core of both these
      models, we review how the final asymptotic states in the Frank model depend
      crucially on whether the system is open or closed, and emphasize the importance
      of temporary chiral excursions, which can and do arise in more complex reaction
      schemes during their approach to chemical equilibrium in closed systems. 

PMID- 22955511
TI  - Chemical and biochemical applications of MALDI TOF-MS based on analyzing the
      small organic compounds.
AB  - This review focuses on the recent applications of matrix-assisted laser
      desorption ionization time of flight mass spectrometry (MALDI TOF-MS)
      technologies for analysis of small molecular compounds (SMCs) on qualitative and
      quantitative levels to provide valuable information for the relative chemical and
      biochemical researches. We summarized the approaches to minimize the interference
      in low m/z range and ion suppression effects by adding chemical reagents, sample
      cleaning and preparation, matrix selection and performing chromatographic
      separation before MALDI TOF-MS analysis. Meanwhile, we discussed the strategies
      to enhance the MALDI TOF-MS detection sensitivity and selectivity by
      derivatization to attach the "charge tags" to SMCs. In addition, the mass
      spectrometric imaging (MSI) methods for locating the target SMCs in bio-tissues
      by MALDI TOF-MS were reviewed. Furthermore, the applications of MALDI TOF-MS for
      monitoring enzyme reactions and the screening of their inhibitors were also
      presented. Finally, the chemical applications of MALDI TOF-MS on characterization
      of small molecular transition-metal complexes and monitoring the organic
      reactions, especially the polymerization reactions, were discussed.

PMID- 22955512
TI  - Marginal vitamin B-6 deficiency decreases plasma (n-3) and (n-6) PUFA
      concentrations in healthy men and women.
AB  - Previous animal studies showed that severe vitamin B-6 deficiency altered fatty
      acid profiles of tissue lipids, often with an increase of linoleic acid and a
      decrease of arachidonic acid. However, little is known about the extent to which
      vitamin B-6 deficiency affects human fatty acid profiles. The aim of this study
      was to determine the effects of marginal vitamin B-6 deficiency on fatty acid
      profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC)
      of healthy adults fed a 28-d, low-vitamin B-6 diet. Healthy participants (n = 23)
      received a 2-d, controlled, vitamin B-6-adequate diet followed by a 28-d, vitamin
      B-6-restricted diet to induce a marginal deficiency. Plasma HDL and LDL
      cholesterol concentrations, FFA concentrations, and erythrocyte and PBMC membrane
      fatty acid compositions did not significantly change from baseline after the 28-d
      restriction. Plasma total arachidonic acid, EPA, and DHA concentrations decreased
      from (mean +/- SD) 548 +/- 96 to 490 +/- 94 MUmol/L, 37 +/- 13 to 32 +/- 13
      MUmol/L, and 121 +/- 28 to 109 +/- 28 MUmol/L [positive false discovery rate
      (pFDR) adjusted P < 0.05], respectively. The total (n-6):(n-3) PUFA ratio in
      plasma exhibited a minor increase from 15.4 +/- 2.8 to 16.6 +/- 3.1 (pFDR
      adjusted P < 0.05). These data indicate that short-term vitamin B-6 restriction
      decreases plasma (n-3) and (n-6) PUFA concentrations and tends to increase the
      plasma (n-6):(n-3) PUFA ratio. Such changes in blood lipids may be associated
      with the elevated risk of cardiovascular disease in vitamin B-6 insufficiency.

PMID- 22955513
TI  - Postprandial spillover of dietary lipid into plasma is increased with moderate
      amounts of ingested fat and is inversely related to adiposity in healthy older
      men.
AB  - Adverse effects on health mediated by increased plasma FFA concentrations are
      well established and older individuals are particularly susceptible to these
      effects. We sought to determine the effects of the amount of dietary fat on
      increasing the plasma FFA concentrations as a result of "spillover" of dietary
      fat into the plasma FFA pool during the postprandial period in older men.
      Healthy, older participants (63-71 y old) were studied in a randomized, crossover
      design following ingestions of low (LF) and moderate (MF) amounts of [1,1,1
      (13)C]-triolein-labeled fat, corresponding to 0.4 and 0.7 g of fat/kg body
      weight, respectively. Spillover of dietary fatty acids into plasma during the 8-h
      postprandial period (AUC; mmol L(-1) h) after MF ingestion was 1.2 times greater
      than that after LF ingestion (2.8 +/- 0.4 vs. 1.2 +/- 0.1; P < 0.05). The
      spillover of dietary fatty acids following the MF, but not the LF, ingestion was
      correlated with the percent body fat (r(s) = -0.89) and percent body fat-free
      mass (r(s) = 0.94) of the men (P < 0.05). After adjusting to the amount of
      ingested fat, the spillover of dietary fatty acids in the MF trial was
      disproportionally higher than that in the LF trial (P < 0.05), but the
      corresponding postprandial plasma TG responses did not differ between trials. In
      conclusion, spillover of dietary lipid into plasma is disproportionally increased
      at higher doses of dietary fat and this response is inversely related to
      adiposity in healthy men of advanced age.

PMID- 22955514
TI  - Plasma alkylresorcinols, biomarkers of whole-grain intake, are related to lower
      BMI in older adults.
AB  - Alkylresorcinols (AR) are phenolic lipids found in the bran fraction of whole
      grain wheat, rye, and barley. In intervention studies, plasma AR concentration
      increased in response to greater intakes of whole grain, wheat, and rye. This
      study examined the cross-sectional associations between plasma AR and habitual
      whole-grain intake, BMI, and metabolic risk factors in 407 free-living older
      adults (166 men and 241 women; aged 60-81y; median BMI: 27 kg/m(2)). Plasma AR
      were measured by liquid chromatography-tandem MS, and whole-grain intakes were
      estimated by using an FFQ. After adjustment for fasting TG concentrations, median
      plasma AR concentrations across quartile categories of AR were 5, 14, 27, and 62
      nmol/L, respectively. Spearman correlation coefficients between plasma AR and
      whole-grain wheat-rich foods and total bran intake were 0.31 and 0.27,
      respectively (both P < 0.0001). After adjustment for multiple covariates, the
      geometric means of BMI in the lowest and highest quartile category of plasma AR
      were 27.6 and 26.7 kg/m(2), respectively (P-trend = 0.04). No associations were
      observed between plasma AR and glucose and insulin. Our study shows a dose
      dependent relationship between whole-grain intake and plasma AR and confirms the
      previously observed inverse relationship between whole-grain intake and BMI using
      an independent biomarker of whole-grain wheat intake.

PMID- 22955515
TI  - Financial management skills are associated with food insecurity in a sample of
      households with children in the United States.
AB  - Food insecurity is one of the leading public health challenges facing children in
      the United States today. Reducing food insecurity and its attendant consequences
      requires an understanding of the determinants of food insecurity. Although
      previous work has greatly advanced our understanding of these determinants, the
      role of one of the oft-speculated important determinants of food insecurity,
      household financial management skills, has not been considered. To address this
      research lacuna, we use a recently conducted survey, the Survey of Household
      Finances and Childhood Obesity, that has information on specific financial
      management practices, impressions of financial management skills, and households'
      food insecurity. The sample included 904 households with children. Within this
      sample, 19.3% were food insecure and, for our central financial management skill
      variable, the mean value was 3.55 on a 5-point scale. Probit regression models
      estimated the probability of a household being food insecure as conditional on
      financial management skills and other covariates. We found a large and
      significant inverse relationship between a respondent's use of specific financial
      management practices and food insecurity and between a respondent's confidence in
      his or her financial management skills and food insecurity. That is, households
      with greater financial management abilities are less likely to be food insecure.
      This finding also holds when the sample is restricted to households with incomes
      <200% of the poverty line. These results suggest that improving households'
      financial management skills has the potential to reduce food insecurity in the
      United States.

PMID- 22955516
TI  - Excess gestational weight gain is associated with child adiposity among mothers
      with normal and overweight prepregnancy weight status.
AB  - There are inconsistencies in the literature regarding the association between
      gestational weight gain (GWG) and child adiposity. GWG is hypothesized to act on
      child adiposity directly through intrauterine programming and indirectly through
      birth weight. It is unclear if the relative importance of these pathways differs
      by prepregnancy BMI status. We analyzed data from 3600 participants of the
      nationally representative Early Childhood Longitudinal Study-Birth Cohort. Child
      BMI Z-score was calculated from height and weight measured at 5 y. Using linear
      regression, controlling for sociodemographics and family lifestyle, we examined
      prepregnancy BMI-specific associations between GWG and child BMI Z-score. There
      was a nonlinear association among normal (P < 0.001) and overweight mothers only
      (P = 0.013), such that GWG beyond the midpoint of the 2009 Institute of Medicine
      recommendations was associated with a significant increase in child BMI Z-score.
      After the addition of birth-weight-for-gestational-age and breastfeeding to the
      model, the association remained among normal-weight mothers (P = 0.005) and was
      slightly attenuated among overweight mothers (P = 0.09). No significant
      association was observed between GWG and child BMI Z-score among underweight or
      obese mothers. We used path analysis to decompose the total effect into direct
      and indirect effects. This indicated the presence of a stronger direct than
      indirect effect. In conclusion, low GWG is not associated with BMI Z-score among
      any prepregnancy BMI group. Excess GWG is associated with an increase in child
      BMI Z-score among normal and overweight mothers only. Prevention of excess GWG
      may be a strategy to prevent childhood obesity.

PMID- 22955517
TI  - Among plant lignans, pinoresinol has the strongest antiinflammatory properties in
      human intestinal Caco-2 cells.
AB  - Dietary lignans show some promising health benefits, but little is known about
      their fate and activities in the small intestine. The purpose of this study was
      thus to investigate whether plant lignans are taken up by intestinal cells and
      modulate the intestinal inflammatory response using the Caco-2 cell model. Six
      lignan standards [secoisolariciresinol diglucoside (SDG), secoisolariciresinol
      (SECO), pinoresinol (PINO), lariciresinol, matairesinol (MAT), and
      hydroxymatairesinol] and their colonic metabolites [enterolactone (ENL) and
      enterodiol] were studied. First, differentiated cells were exposed to SDG, SECO,
      PINO, or ENL at increasing concentrations for 4 h, and their cellular contents
      (before and after deconjugation) were determined by HPLC. Second, in IL-1beta
      stimulated confluent and/or differentiated cells, lignan effects were tested on
      different soluble proinflammatory mediators quantified by enzyme immunoassays and
      on the NF-kappaB activation pathway by using cells transiently transfected. SECO,
      PINO, and ENL, but not SDG, were taken up and partly conjugated by cells, which
      is a saturable conjugation process. PINO was the most efficiently conjugated (75%
      of total in cells). In inflamed cells, PINO significantly reduced IL-6 by 65% and
      30% in confluent and differentiated cells, respectively, and cyclooxygenase (COX)
      2-derived prostaglandin E(2) by 62% in confluent cells. In contrast, MAT
      increased significantly COX-2-derived prostaglandin E(2) in confluent cells.
      Moreover, PINO dose-dependently decreased IL-6 and macrophage chemoattractant
      protein-1 secretions and NF-kappaB activity. Our findings suggest that plant
      lignans can be absorbed and metabolized in the small intestine and, among the
      plant lignans tested, PINO exhibited the strongest antiinflammatory properties by
      acting on the NF-kappaB signaling pathway, possibly in relation to its furofuran
      structure and/or its intestinal metabolism.

PMID- 22955518
TI  - Pre-eclampsia and pregnancy-induced hypertension are associated with severe
      diabetic retinopathy in type 1 diabetes later in life.
AB  - To investigate whether pre-eclampsia (PE) or pregnancy-induced hypertension (PIH)
      predicts the development of severe diabetic retinopathy (SDR) in type 1 diabetes.
      Altogether, 203 women with type 1 diabetes who were followed during pregnancy
      were re-examined within the Finnish Diabetic Nephropathy Study. After excluding
      patients with pre-pregnancy hypertension and those who had had laser treatment or
      whose retinopathy was graded as proliferative at the index pregnancy, 158 were
      prospectively studied. As a surrogate marker for SDR, retinal laser
      photocoagulation was used. The time from pregnancy to SDR (N = 21) or follow-up
      was 16 years (interquartile range, 11-19). HbA1c was repeatedly measured both
      during pregnancy and follow-up. Women with prior PE (26 % vs. 6 %, P = 0.003) or
      PIH (24 % vs. 6 %, P = 0.008) had more often incident SDR during follow-up
      compared to those with normotensive pregnancy. The hazard ratios (HR) remained
      associated with the progression to SDR after adjustment for duration of diabetes
      and diabetic nephropathy in a Cox regression analysis [PE: 3.5 (95 % CI 1.1
      10.9); P = 0.03 and for PIH: 3.2 (1.1-9.8); P = 0.04]. The association between
      PIH and incident SDR did not change after inclusion of mean HbA1c, measured
      during pregnancy (all 3 trimesters) and serial HbA1c measurements during follow
      up, 3.5 (1.1-11.8; P = 0.03). However, in a similar model, the HR for PE was no
      more significant 2.0 (0.6-6.8; P = NS). The results suggest that women with type
      1 diabetes and a hypertensive pregnancy have an increased risk of severe diabetic
      retinopathy later in life. 

PMID- 22955519
TI  - Coagulation on endothelial cells: the underexposed part of Virchow's Triad.
AB  - The process of thrombin generation involves numerous plasma proteases and
      cofactors. Interaction with the vessel wall, in particular endothelial cells
      (ECs), influences this process but data on this interaction is limited. We
      evaluated thrombin generation on EA.hy926, human coronary arterial ECs (HCAECs)
      and patient-derived human venous ECs (HVECs) by means of a modified calibrated
      automated thrombogram (CAT) method and especially looked into contribution of the
      intrinsic and extrinsic pathways. Thrombin generation was measured in presence of
      confluent ECs with normal pooled and factor XII-deficient (FXII-deficient)
      platelet-poor plasma, with/without active site inhibited factor VIIa (ASIS) to
      block the extrinsic pathway and corn trypsin inhibitor for blocking contact
      activation (intrinsic pathway). Fetal bovine serum (FBS) was removed from culture
      conditions as FXIIa from the serum retained on ECs apparently, thereby inducing
      strong contact activation. In serum-free conditions, EA.hy926 and patient-derived
      HVECs induced thrombin generation mainly via the contact activation pathway with
      minor influence of ASIS on peak height and very low thrombin generation curves in
      FXII-deficient plasma. HVECs derived from coronary arterial bypass graft (CABG)
      patients showed increased thrombin generation compared to control patients, which
      could be ascribed to increased contact activation. Contribution of the extrinsic
      pathway on patient-derived ECs was limited. We conclude that the CAT method in
      combination with serum-free cultured ECs offers a valuable high-throughput method
      to evaluate endothelial influences on thrombin generation, which appears to
      involve predominantly contact activation on ECs. Contact activation-mediated
      thrombin generation was increased on ECs from CABG patients compared to controls.

PMID- 22955520
TI  - Pyogenic granuloma, an impaired wound healing process, linked to vascular growth
      driven by FLT4 and the nitric oxide pathway.
AB  - Pyogenic granuloma, also called lobular capillary hemangioma, is a condition
      usually occurring in skin or mucosa and often related to prior local trauma or
      pregnancy. However, the etiopathogenesis of pyogenic granuloma is poorly
      understood and whether pyogenic granuloma being a reactive process or a tumor is
      unknown. In an attempt to clarify this issue, we performed genome-wide
      transcriptional profiling of laser-captured vessels from pyogenic granuloma and
      from a richly vascularized tissue, placenta, as well as, from proliferative and
      involutive hemangiomas. Our study identified a gene signature specific to
      pyogenic granuloma. In the serial analysis of gene expression (SAGE) database,
      this signature was linked to 'white blood cells monocytes'. It also demonstrated
      high enrichment for gene ontology terms corresponding to 'vasculature
      development' and 'regulation of blood pressure'. This signature included genes of
      the nitric oxide pathway alongside genes related to hypoxia-induced angiogenesis
      and vascular injury, three conditions biologically interconnected. Finally, one
      of the genes specifically associated with pyogenic granuloma was FLT4, a tyrosine
      kinase receptor related to pathological angiogenesis. All together, these data
      advocate for pyogenic granuloma to be a reactive lesion resulting from tissue
      injury, followed by an impaired wound healing response, during which vascular
      growth is driven by FLT4 and the nitric oxide pathway.

PMID- 22955521
TI  - Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal
      tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are usually driven by mutations in KIT or
      PDGFRA, although 15% of GISTs in adults and >90% in children lack such mutations.
      The majority of gastric KIT/PDGFRA wild-type GISTs show distinctive morphological
      and clinical features and loss of expression of succinate dehydrogenase (SDH) B.
      Only a small subset of SDHB-deficient GISTs carries loss-of-function mutations in
      SDHB, SDHC, or SDHD. Because of the complexity of its locus (15 exons) and the
      presence of three pseudogenes, SDHA is rarely analyzed. Recently, mutations in
      SDHA were shown to lead to loss of expression of SDHA in a small group of
      paragangliomas. We sought to determine whether immunohistochemistry for SDHA
      could identify GISTs with SDHA mutations. Tumors (n=33) with pathological
      features of SDH-deficient GIST were analyzed for expression of SDHA and SDHB by
      immunohistochemistry, and SDHA exons were sequenced from tumors lacking SDHA
      expression. Exons harboring somatic mutations were examined in DNA from
      corresponding normal tissue. All 33 tumors showed loss of SDHB expression. A
      total of 9 out of 33 (27%) tumors also lacked expression of SDHA. SDHA-deficient
      GISTs affected five men and four women (median age 38 years). SDHA expression was
      intact in the 24 remaining tumors, including those with known SDHB (n=3) or SDHC
      (n=2) mutations. Nonsense (n=8) or missense (n=1) mutations in SDHA were
      identified in all SDHA-deficient tumors. Heterozygous mutations were also found
      in DNA from normal tissues from six patients with available material. Somatic
      loss of the second allele has been found in seven tumors, five by loss of
      heterozygosity, one by a 13-bp deletion, and one by a missense mutation. Loss of
      SDHA expression in GIST reliably predicts the presence of SDHA mutations, which
      represent a relatively common cause of SDH-deficient GIST in adults.
      Immunohistochemistry for SDHA can be used to select patients for SDHA-specific
      genetic testing.

PMID- 22955522
TI  - Inhibited PTHLH downstream leukocyte adhesion-mediated protein amino acid N
      linked glycosylation coupling Notch and JAK-STAT cascade to iron-sulfur cluster
      assembly-induced aging network in no-tumor hepatitis/cirrhotic tissues (HBV or
      HCV infection) by systems-theoretical analysis.
AB  - We analyzed the different biological processes and occurrence numbers between low
      expression inhibited PTHLH downstream-mediated aging gene ontology (GO) network
      of no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) and the
      corresponding high expression (fold change >=2) inhibited GO network of human
      hepatocellular carcinoma (HCC). Inhibited PTHLH downstream-mediated aging network
      consisted of aging, branched chain family amino acid biosynthesis, cellular
      metabolism, cholesterol biosynthesis, coupled to cyclic nucleotide second
      messenger, cytolysis, 'de novo' GDP-l-fucose biosynthesis, detection of
      mechanical stimulus, glucose homeostasis, G-protein signaling, leukocyte
      adhesion, iron-sulfur cluster assembly, JAK-STAT cascade, Notch signaling
      pathway, nucleotide-sugar metabolism, peptidyl-tyrosine sulfation, protein amino
      acid N-linked glycosylation, protein amino acid phosphorylation, response to
      drug, rRNA processing, translational initiation, ubiquitin-dependent protein
      catabolism, homophilic cell adhesion in no-tumor hepatitis/cirrhotic tissues. We
      proposed inhibited PTHLH downstream leukocyte adhesion-mediated protein amino
      acid N-linked glycosylation coupling Notch and JAK-STAT cascade to iron-sulfur
      cluster assembly-induced aging network. Our hypothesis was verified by the same
      inhibited PTHLH downstream-mediated aging GO network in no-tumor
      hepatitis/cirrhotic tissues with the corresponding activated GO network of HCC,
      or the different with the corresponding activated GO network of no-tumor
      hepatitis/cirrhotic tissues. Inhibited PTHLH downstream leukocyte adhesion
      mediated protein amino acid N-linked glycosylation coupling Notch and JAK-STAT
      cascade to iron-sulfur cluster assembly-induced aging network included TSTA3,
      ALK, CIAO1, NOTCH3 in no-tumor hepatitis/cirrhotic tissues from the GEO data set
      using gene regulatory network inference method and our programming.

PMID- 22955523
TI  - The Grossman model after 40 years.
AB  - This editorial presents a critical review of the health model pioneered by
      Michael Grossman (MGM) in 1972 [8]. It argues that whereas the MGM has great
      charm for economists, it fails to achieve acceptance by interested laypersons and
      policy makers. The main reasons for this failure are: (1) the assumption of a
      long and fixed planning horizon, (2) a fixed ratio between individuals healthcare
      expenditure and the cost of their own health-enhancing efforts regardless of
      their state of health, and (3) their presumed ability to restore the state of
      health deemed optimal at a speed that does not depend on their state of health.
      An alternative formulation emphasizing the stochastic nature of health production
      is sketched that conceptually provides solutions to these three problems. In
      addition, it permits discarding a popular medical argument that seems to
      undermine the very basis of welfare analysis applied to health by claiming
      preferences to be unstable: "As long as you are healthy, you don't give a damn,
      but as soon as you are sick, you are prepared to sacrifice everything to restore
      your health." The editorial concludes by outlining a research program that may
      help health economists break away from their MGM fixation.

PMID- 22955524
TI  - The present state of health economics: a critique and an agenda for the future.

PMID- 22955525
TI  - The role of backward mutations on the within-host dynamics of HIV-1.
AB  - The quality of life for patients infected with human immunodeficiency virus (HIV
      1) has been positively impacted by the use of antiretroviral therapy (ART).
      However, the benefits of ART are usually halted by the emergence of drug
      resistance. Drug-resistant strains arise from virus mutations, as HIV-1 reverse
      transcription is prone to errors, with mutations normally carrying fitness costs
      to the virus. When ART is interrupted, the wild-type drug-sensitive strain
      rapidly out-competes the resistant strain, as the former strain is fitter than
      the latter in the absence of ART. One mechanism for sustaining the sensitive
      strain during ART is given by the virus mutating from resistant to sensitive
      strains, which is referred to as backward mutation. This is important during
      periods of treatment interruptions as prior existence of the sensitive strain
      would lead to replacement of the resistant strain. In order to assess the role of
      backward mutations in the dynamics of HIV-1 within an infected host, we analyze a
      mathematical model of two interacting virus strains in either absence or presence
      of ART. We study the effect of backward mutations on the definition of the basic
      reproductive number, and the value and stability of equilibrium points. The
      analysis of the model shows that, thanks to both forward and backward mutations,
      sensitive and resistant strains co-exist. In addition, conditions for the
      dominance of a viral strain with or without ART are provided. For this model,
      backward mutations are shown to be necessary for the persistence of the sensitive
      strain during ART. 

PMID- 22955526
TI  - Early onset scoliosis:  modern treatment and results.
AB  - BACKGROUND: Early onset scoliosis (EOS) is a potentially fatal, challenging group
      of diseases the management of which has markedly changed in the last decade. The
      purpose of this review is to provide the reader with a brief description of each
      of these new therapeutic modalities, their indications for use, and early
      clinical results. METHODS: A systematic review of peer-reviewed publications and
      abstracts related to the treatment of EOS in the last decade was carried out and
      synthesized into a review of modern treatment methods. RESULTS: Recent advances
      in techniques and understanding of preserving the thoracic space have improved
      the morbidity and mortality of children with progressive EOS. Derotational
      casting may be used in younger patients with curves between 25 and 60 degrees.
      The vertical expandable prosthetic titanium rib is best suited for patients with
      thoracic insufficiency syndrome. Single or dual growing rods may be used alone or
      in combination with vertical expandable prosthetic titanium rib to treat patients
      with progressive EOS who are not candidates for casting. Shilla technique is an
      alternative to growing rods that avoids the morbidity of repeated lengthenings
      but is not as well proven as the techniques described above. Other methods such
      as automatic growing rods and growth modulation techniques are still
      investigational, and their role needs to be defined after further study.
      CONCLUSIONS: Recent advances have improved the treatment of children with EOS.
      Treatment continues to be challenging with complication rates higher than
      treatment of idiopathic scoliosis. LEVEL OF EVIDENCE: Level V.

PMID- 22955527
TI  - The role of serial casting in early-onset scoliosis (EOS).
AB  - BACKGROUND: Serial casting has demonstrated efficacy for idiopathic early-onset
      scoliosis (EOS). Results of casting in nonidiopathic (syndromic and congenital)
      EOS patients have not previously been well described. METHODS: A total of 53
      patients underwent serial casting for EOS from 2005 to 2010 at a single
      institution. Deformity was classified as idiopathic or nonidiopathic. Diagnosis,
      time in cast, number of casts, use of bracing, complications, and outcomes were
      recorded. Radiographic measures included Cobb angle and thoracic height (T1-T12).
      Thoracic height velocity was calculated and compared with established norms.
      RESULTS: A total of 36 patients, 19 idiopathic and 17 nonidiopathic (14
      syndromic, 3 congenital), completed cast treatment and had >6-month follow-up and
      were therefore included. Of those, 17% (6/36) experienced resolution of their
      deformity, 53% (19/26) are currently in braces, and 31% (11/36) had undergone
      surgery. Surgery occurred on average at age 5.6 years and was delayed by an
      average of 2.1 years from time of first cast. A 19% complication was observed.
      There was no statistical difference in the rate of resolution of deformity
      between idiopathic (5/19) and nonidiopathic (1/17) patients (P=0.182), although
      there exists a trend toward greater curve correction in idiopathic patients.
      Surgery occurred in fewer patients (2/19) in the idiopathic group compared with
      the nonidiopathic group (9/17) (P=0.006). Significant improvements in Cobb angle
      was observed in the idiopathic group (12.2 degrees) during casting (P=0.003).
      Nonidiopathic patients did not maintain the correction gained during casting at
      the time of final follow-up. T1-T12 height increased across all study patients
      regardless of etiology during the period of casting at similar velocity to
      established norms of 1.4 cm/y for this age group. CONCLUSIONS: Serial casting
      offers modest deformity correction in idiopathic deformities compared with
      nonidiopathic deformities. Thoracic height growth continued throughout the
      casting period at normal velocity. Serial casting maintained normal longitudinal
      thoracic growth in all patients with EOS in this cohort. Although many required
      surgery, the increased thoracic height may have positive implications on ultimate
      pulmonary function. LEVEL OF EVIDENCE: Therapeutic level III.

PMID- 22955528
TI  - Serial casting as a delay tactic in the treatment of moderate-to-severe early
      onset scoliosis.
AB  - BACKGROUND: Serial casting can cure mild infantile idiopathic scoliosis. Its use
      in delaying surgery in older children and those with larger curves or syndromes
      is poorly defined. METHODS: A review of a single center's experience with casting
      was performed. Patients were included if they had a syndromic, neuromuscular, or
      congenital scoliosis or were older than 2.5 years with an idiopathic scoliosis
      measuring >50 degrees. RESULTS: A retrospective review was performed on 29
      patients meeting all inclusion criteria. Of these, 12 were idiopathic and 17 were
      nonidiopathic curves. Average age at first cast was 4.4 +/- 2.1 years, and 3.0 +/
      1.8 cast changes were performed over 1.4 +/- 1.1 years. Patients were
      transitioned to a brace and followed up for 5.5 years (range, 2.2 to 11.4 y). The
      main thoracic Cobb angle before casting was 68.8 +/- 12.3 degrees, which
      corrected to 39.1 +/- 16.4 degrees in a cast. Cobb angle after cast removal was
      60.9 +/- 18.4 degrees, which increased to 76.3 +/- 24.0 degrees at final follow
      up. T1-T12 height increased to 1.1 +/- 2.6 cm during the treatment period
      (P=0.05). There were 5 minor complications. Fifteen patients (51.7%) required
      surgical treatment for their scoliosis at most recent follow-up and an additional
      7 patients (24.1%) were delayed until a definitive anterior/posterior spinal
      fusion could be performed. Surgery was delayed 39 +/- 25 months from the first
      cast. Growing rods were required in 8 patients (27.6%). The patients who
      ultimately underwent surgical intervention (SG) were more likely to have a larger
      postcasting residual main thoracic Cobb angle than those who did not require
      surgery [NS; 69.5 +/- 14.6 degrees (SG) vs. 51.6 +/- 17.9 degrees (NS), P=0.007]
      and had a greater progression of their curves after cast removal [20.9 +/- 13.5
      degrees (SG) vs. 9.4 +/- 11.0 degrees (NS), P=0.02]. CONCLUSIONS: Serial casting
      is a viable alternative to surgical growth sparing techniques in moderate-to
      severe early-onset scoliosis and may help delay eventual surgical intervention.
      Although a cure cannot be expected, an average of 39 months of delay was achieved
      in this patient cohort and 72.4% have avoided growing spine surgery. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 22955529
TI  - Postoperative radiographs after pinning of supracondylar humerus fractures:  are
      they necessary?
AB  - BACKGROUND: The purpose of this study was to evaluate the necessity of early
      postoperative radiographs after pinning of supracondylar humerus fractures by
      determining both the percentage of patients who displayed change in fracture
      fixation and whether these changes affected their outcome. METHODS: A series of
      643 consecutive patients who underwent operative management of Gartland type II
      and III fractures at our institution between January 2002 and December 2010 were
      reviewed. Demographic data were obtained through chart review, including age,
      sex, extremity, fracture type, and mechanism. Intraoperative fluoroscopic images
      were compared with postoperative radiographs to identify changes in fracture
      alignment and pin placement. RESULTS: A total of 643 patients (320 females, 323
      males) with a mean age of 6.1 years (range, 1.1 to 16.0) were reviewed. Fifty
      seven percent of fractures were classified as type II and 43% were type III. The
      overall complication rate was 8.8% (57/643). Pin backout or fracture translation
      was seen in 32 patients (4.9%) at the first postoperative visit. All of these
      patients sustained type III fractures. One of these patients required further
      operative management. Patients with changes in pin or fracture alignment did not
      demonstrate a statistically significant difference in time to first postoperative
      visit (P=0.23), days to pin removal (P=0.07), or average follow-up time (P=0.10).
      Fracture severity did not correlate with change in alignment (P=0.952). No
      postoperative neurological complications were observed in patients with alignment
      changes. CONCLUSIONS: Mild alignment changes and pin migration observed in
      postoperative radiographs after pinning of supracondylar humerus fractures have
      little effect on clinical management parameters or long-term sequelae.
      Radiographs can therefore be deferred until the time of pin removal provided
      adequate intraoperative stability was obtained. LEVEL OF EVIDENCE: Level IV.

PMID- 22955530
TI  - Type II supracondylar humerus fractures: can some be treated nonoperatively?
AB  - BACKGROUND: The range of injury severity that can be seen within the category of
      type II supracondylar humerus fractures (SCHFs) raises the question whether some
      could be treated nonoperatively. However, the clinical difficulty in using this
      approach lies in determining which type II SCHFs can be managed successfully
      without a surgical intervention. METHODS: We reviewed clinical and radiographic
      information on 259 pediatric type II SCHFs that were enrolled in a prospective
      registry of elbow fractures. The characteristics of the patients who were treated
      without surgery were compared with those of patients who were treated surgically.
      Treatment outcomes, as assessed by the final clinical and radiographic alignment,
      range of motion of the elbow, and complications, were compared between the groups
      to define clinical and radiographic features that related to success or failure
      of nonoperative management. RESULTS: During the course of treatment, 39 fractures
      were found to have unsatisfactory alignment with nonoperative management and were
      taken for surgery. Ultimately, 150 fractures (57.9%) were treated nonoperatively,
      and 109 fractures (42.1%) were treated surgically. At final follow-up, outcome
      measures of change in carrying angle, range of motion, and complications did not
      show clinically significant differences between treatment groups. Fractures
      without rotational deformity or coronal angulation and with a shaft-condylar
      angle of >15 degrees were more likely to be associated with successful
      nonsurgical treatment. A scoring system was developed using these features to
      stratify the severity of the injury. Patients with isolated extension deformity,
      but none of the other features, were more likely to complete successful
      nonoperative management. CONCLUSIONS: This study suggests that some of the less
      severe pediatric type II SCHFs can be successfully treated without surgery if
      close follow-up is achieved. Fractures with initial rotational deformity, coronal
      malalignment, and significant extension of the distal fragment are likely to fail
      a nonoperative approach. An algorithm using the initial radiographic
      characteristics can aid in distinguishing groups.

PMID- 22955531
TI  - Pediatric physeal slide-traction plate fixation for comminuted distal femur
      fractures in children.
AB  - BACKGROUND: Operative stabilization without inhibiting epiphyseal growth of
      pediatric comminuted distal femur fractures presents specific challenges. The
      purpose of this study was to evaluate the clinical efficacy of pediatric physeal
      slide-traction plate (PPSP) fixation for comminuted distal femur fractures in
      children. METHODS: We prospectively followed 16 children who were managed PPSP
      for the treatment of comminuted distal femur fractures between 2005 and 2009.
      There were 9 boys with a mean age of 10.4 years (range, 8 to 14 y) and 7 girls
      with a mean age of 9.9 years (range, 6 to 12 y). The mean follow-up was 36.4
      months (range, 18 to 54 mo). RESULTS: There were no intraoperative complications
      related to this technology. All patients were healed, and the mean time was 10.1
      weeks (range, 8 to 13 wk). X-ray analysis of the injured limb revealed that the
      PPSP could be extended as the femur grew, with a mean sliding length of 5.6 mm
      (range, 3 to 15 mm). All patients had excellent final outcomes, and had the
      plates removed with no noted complications except 1 patient who had valgus
      malalignment of 10 degrees at 6 months after the plate removal, which was of no
      clinical concern and required no intervention. CONCLUSIONS: These findings
      suggest that PPSP is a safe and effective treatment for children with comminuted
      distal femur fractures that can be extended as the epiphyseal plate grows with
      reliable internal fixation. LEVEL OF EVIDENCE: Therapeutic level IV.

PMID- 22955532
TI  - Risk factors for redisplacement of pediatric distal forearm and distal radius
      fractures.
AB  - BACKGROUND: Fractures of the distal forearm and distal radius represent the most
      common types of fracture in the pediatric population, with the majority treated
      by closed reduction and cast. Redisplacement has been known to occur in up to 39%
      of cases. There have been numerous risk factors and radiologic indices put
      forward as methods of predicting redisplacement, but this topic remains a matter
      of debate. This retrospective study aims to further assess the significance of
      the many factors in redisplacement after treatment with closed reduction.
      METHODS: This retrospective study included 155 children with distal radius and
      forearm fractures. Age, sex, location of fracture, angulation, displacement, an
      associated ulna fracture, obliquity of fracture, and accuracy of reduction were
      measured for assessment as potential risk factors. In addition, the cast index,
      padding index, Canterbury index, second metacarpal-radius index, gap index, and 3
      point index were measured on postreduction radiographs. RESULTS: Redisplacement
      occurred in 33 of the 155 cases (21.3%). Initial displacement and accuracy of the
      reduction were identified as significant risk factors for redisplacement. Initial
      displacement of >50% (of the radius width) was significantly associated with
      redisplacement (odds ratio of 5.4). Failure to achieve anatomic reduction was
      significantly higher in the redisplacement group (odds ratio 3.9). The only
      radiologic index that differed significantly between groups was the cast index,
      with more patients without redisplacement meeting the cut-off value (60% vs. 32%,
      P=0.010). DISCUSSION: Initial displacement of >50% and inability to achieve
      anatomic reduction are major risk factors for redisplacement. Given its
      effectiveness and ease of clinical application, the cast index remains the most
      useful measure of cast molding. LEVEL OF EVIDENCE: Level II--Retrospective
      prognostic study.

PMID- 22955533
TI  - Arthrogram-assisted fixation of slipped capital femoral epiphysis: a CT and
      radiographic study.
AB  - BACKGROUND: Intraoperative fluoroscopy does not always provide the operating
      surgeon with optimal visualization of a slipped capital femoral epiphysis (SCFE).
      Arthrography can be used to enhance fluoroscopic images of these patients. This
      study retrospectively compared the screw placement between patients who received
      conventional versus arthrographic-assisted in situ screw fixation for SCFE.
      METHODS: We reviewed the charts and radiographs of all patients diagnosed with a
      SCFE at our institution from 2005 to 2010. We isolated those who received
      postoperative computed tomography (CT) scans to confirm screw placement, and
      subdivided the patients into 2 groups: those who received arthrograms to
      facilitate screw placement and those who did not. The screw-tip-to-articular
      surface distance was then measured on intraoperative fluoroscopic images and
      postoperative CT scans. RESULTS: Seventy-eight patients met inclusion criteria
      and 24 received an intraoperative arthrogram. Screw placement determined by
      intraoperative fluoroscopic images did not differ between the 2 groups. When
      measured on postoperative CT scans the screw-tip-to-articular-surface distance
      was significantly smaller in the arthrogram-assisted cohort (2.8 vs. 5.2 mm), and
      the difference between intraoperative and postoperative measurements was
      significantly greater in the arthrogram-assisted cohort (4.9 vs. 1.6 mm). No
      cases of intra-articular screw placement were found in either cohort, nor were
      there any cases demonstrating loss of fixation. CONCLUSIONS: Arthrogram-assisted
      fixation of SCFE is a safe and effective tool in patients whose body habitus
      makes diagnostic fluoroscopic images difficult to obtain. It is, however, not
      without technical challenges. After the dye is injected it becomes more difficult
      to visualize the subchondral bone on fluoroscopic images. Our screws were, on
      average, 4.9 mm closer to the joint space on CT scans than seen intraoperatively.
      The operating surgeon must be aware of this fact to avoid joint penetration.
      LEVEL OF EVIDENCE: Level III.

PMID- 22955534
TI  - Operative versus nonoperative treatments for Legg-Calve-Perthes disease: a meta
      analysis.
AB  - BACKGROUND: Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis
      of the femoral head primarily affecting children of ages 4 to 12 years. There is
      no clear consensus on nonoperative or operative treatment protocols for pediatric
      patients presenting with LCPD. This study uses meta-analysis and a binary
      logistic regression model to analyze the radiographic outcomes of these treatment
      modalities in pediatric patients. METHODS: Clinical studies describing patients
      undergoing either nonoperative or operative treatment of LCPD published from 1960
      through 2010 were searched electronically and manually. Eligible studies
      consisted of (1) a minimum of 10 patients; (2) listed age at the time of
      diagnosis or treatment; (3) performed an initial severity assessment using the
      Herring or Catterall classification; (4) detailed the type of intervention; and
      (5) reassessment of radiographic outcome after a minimum of 1 year after
      treatment using the Mose or Stulberg classification. RESULTS: Twenty-three
      studies, 1232 patients, and 1266 hips met the inclusion criteria. Among patients
      younger than 6 years, operative and nonoperative treatments are equally as likely
      to results in a successful radiographic outcome [odds ratio (OR)=1.071; P=0.828;
      95% confidence interval (CI), 7.377-32.937]. In patients older than 6 years,
      operative treatment is nearly twice as likely to result in a successful
      radiographic outcome (OR=1.754; P<0.0001; 95% CI, 1.299-2.370). For age at
      treatment less than 6 years, a patient treated with a pelvic rather than femoral
      procedure was approximately 5 times as likely to have a good radiographic outcome
      (chi=4.488; P=0.034; unadjusted OR=5.20; 95% CI, 1.021-26.471). Among patients
      ages 6 or older, pelvic procedures were equally as likely as femoral procedures
      to yield a successful radiographic outcome (chi=1.845; P=0.174; unadjusted
      OR=1.329; 95% CI, 0.881-2.004). Sex had no significant influence on radiographic
      outcome (OR=1.248; P=0.486; 95% CI, 0.670-2.325). CONCLUSIONS: This meta-analysis
      suggests that operative treatment is more likely to yield a spherical congruent
      femoral head than nonoperative methods among patients 6 years or older. Among
      patients younger than 6 years, operative and nonoperative methods have the same
      likelihood to yield a good outcome. Patients who were 6 years or older were
      treated operatively, and had the same likelihood of a good radiographic outcome
      regardless of treatment with femoral or pelvic procedures. Among patients younger
      than 6 years, pelvic procedures were more likely to result in a good radiographic
      outcome than femoral procedures. LEVEL OF EVIDENCE: Level IV meta-analysis.

PMID- 22955535
TI  - Treatment of idiopathic clubfoot: experience with the Mitchell-Ponseti brace.
AB  - OBJECTIVE: The Mitchell-Ponseti (MP) foot abduction orthosis was introduced to
      provide a more user-friendly alternative to the traditional Denis-Browne (DB)
      brace in the treatment of idiopathic clubfoot. We describe our experience with
      the effectiveness of the MP brace to maintain correction of clubfeet corrected
      using the Ponseti method. METHODS: We evaluated 57 consecutive infants with 84
      idiopathic clubfeet who were treated using the Ponseti method. After initial
      correction of the deformity was obtained, all infants were placed in the MP
      brace. RESULTS: The patients were followed for a minimum of 2 years (mean, 37.9
      mo; range, 24 to 56 mo). Seventy-nine feet (94%) had heel-cord tenotomy or
      lengthening. The families of 34 (60%) patients were adherent with the
      postcorrective brace protocol. Skin problems were observed in 8 patients (14%), 6
      of which were superficial dorsal skin abrasion, and none of the sandals required
      customization by an orthotist. A recurrence occurred in 40 feet (48%). Correction
      was regained with manipulation and cast application in all cases. Nineteen feet
      (23%) in 14 patients have had, or are scheduled for, an anterior tibial tendon
      transfer. At latest follow-up, all feet were plantigrade and had at least 10
      degrees of dorsiflexion. None of the patients required surgical releases. Of 31
      patients followed for at least 3 years, 26 (84%) used the brace for a minimum of
      3 years. CONCLUSIONS: Using the MP foot abduction orthosis, we were able to
      achieve compliance rates that were at least comparable with those of earlier
      reports using the DB brace. Families found the brace easy to use. The MP brace
      may be considered a useful alternative to the DB brace. LEVEL OF EVIDENCE: Level
      II--prospective.

PMID- 22955536
TI  - Comparison of structural bone autografts and allografts in pediatric foot
      surgery.
AB  - BACKGROUND: Autogenous bone has been the gold standard as the source for
      structural bone-graft material due to its osteogenic potential,
      nonimmunogenicity, and efficiency of incorporation. However, donor-site morbidity
      can lead to significant problems. Allograft bone is readily available and
      obviates the risks associated with bone-graft harvesting. However, its use raises
      concerns of disease transmission, infection, slower incorporation, and
      immunologic reaction. Despite these concerns, allograft use has become
      widespread. The few comparative studies of the 2 graft types used in spine and
      tumor surgery are promising. We sought to compare the speed and completeness of
      graft incorporation and the relative safety of autograft and allograft structural
      bone in pediatric foot surgery. METHODS: A retrospective analysis was performed
      on 161 children who underwent foot surgery requiring 182 allografts and 63
      autografts from 1982 to 1994. Follow-up ranged from 2 to 146 months (mean=51.4).
      RESULTS: Graft-host union, defined as radiographic evidence of healing with a
      clinical lack of tenderness at graft insertion site, occurred within 12 weeks in
      both groups. Average time to healing in both groups was just over 7 weeks. In the
      allograft group, there was 1 nonunion, 3 graft displacements due to technical
      error requiring reoperation, and 1 partial displacement that did not require
      reoperation. All of these complications can be attributed to technique rather
      than to graft type. There were no infections or instances of disease
      transmission. There were no reported complications in the autograft group.
      CONCLUSIONS: Small, structural bone allografts provide a safe, efficient, and
      cost-effective alternative to iliac crest bone autograft in pediatric foot
      surgery. LEVELS OF EVIDENCE: Level III, therapeutic study, retrospective
      comparative study.

PMID- 22955537
TI  - Pediatric trigger thumb with locked interphalangeal joint:  can observation or
      splinting be a treatment option?
AB  - BACKGROUND: The purpose of this study is to report the natural history of
      pediatric trigger thumb with locked interphalangeal joint, the efficacy of a
      splint for this condition, and the outcome of late surgery. METHODS: Medical
      records of 64 patients were retrospectively reviewed. Patients were treated with
      a coil splint when parents and patients accepted; otherwise, regular observation
      was conducted. Splint application and/or observation were terminated either when
      the patient gained full range of active motion without snapping, or underwent
      surgical intervention. RESULTS: In splint group, 92% of the patients experienced
      complete symptom relief in 22 months, whereas 60% resolved completely in 59
      months in observation group. The differences were statistically significant. One
      thumb in a patient with bilateral involvement remained locked while the other
      completely resolved. The rest of the patients also showed improved symptom from
      locking to snapping. Four patients with residual snapping underwent surgery at
      the age of 8 years and above without any deformity and complication. CONCLUSIONS:
      Splint was efficient in shortening the time for symptom relief; however, the
      natural history revealed the self-limiting nature of this condition. Late surgery
      was safe and effective for residual snapping and can be presented as one
      treatment option to the patients and families, combined with conservative
      treatment. LEVEL OF EVIDENCE: Level III--retrospective comparative study.

PMID- 22955538
TI  - Hand and upper limb anomalies in Poland syndrome: a new proposal of
      classification.
AB  - BACKGROUND: The Poland anomaly (PA) comprises unilateral absence or hypoplasia of
      the pectoralis major muscle and a variable degree of ipsilateral hand and upper
      limb anomalies. Various hand and upper limb anomalies classifications in PA have
      been previously published. In this work, a new classification of hand and upper
      limb anomalies in PA is proposed, on the basis of the clinical and instrumental
      evaluation of 175 patients. METHODS: The patients have been followed by a
      multidisciplinary approach, consisting in orthopaedic, surgical, and genetic
      evaluation and chest, upper limb, and ultrasound examination of major and minor
      pectoralis muscles, heart, and kidney. RESULTS: Hand and upper limb anomalies
      were classified in 8 groups on the basis of the clinical degree of severity and
      on the basis of the presence of coexisting associated anomalies. Data regarding
      the sex and laterality, previously reported in the medical literature, were
      confirmed by our analysis. Etiopathogenetic mechanisms leading to the anomaly are
      discussed. CONCLUSIONS: The proposed classification is derived from the
      observation of the widest group of patients described in the medical literature.
      Our proposal could help in the management of patients affected by Poland syndrome
      and in understanding etiological and pathologic aspects of the disease. LEVEL OF
      EVIDENCE: IV.

PMID- 22955539
TI  - How many referrals to a pediatric orthopaedic hospital specialty clinic are
      primary care problems?
AB  - PURPOSE: Many primary care physicians believe that there are too few pediatric
      orthopaedic specialists available to meet their patients' needs. However, a
      recent survey by the Practice Management Committee of the Pediatric Orthopaedic
      Society of North America found that new referrals were often for cases that could
      have been managed by primary care practitioners. We wished to determine how many
      new referral cases seen by pediatric orthopaedic surgeons are in fact conditions
      that can be readily managed by a primary care physician should he/she chose to do
      so. METHODS: We prospectively studied all new referrals to our hospital-based
      orthopaedic clinic during August 2010. Each new referral was evaluated for
      whether it met the American Board of Pediatrics criteria for being a condition
      that could be managed by a primary care pediatrician. Each referral was also
      evaluated for whether it met the American Academy of Pediatrics Surgery Advisory
      Panel guidelines recommending referral to an orthopaedic specialist, regardless
      of whether it is for general orthopaedics or pediatric orthopaedics. On the basis
      of these criteria, we classified conditions as either a condition manageable by
      primary care physicians or a condition that should be referred to an orthopaedic
      surgeon or a pediatric orthopaedic surgeon. We used these guidelines not to
      identify diagnosis that primary care physicians should treat but, rather, to
      compare the guideline-delineated referrals with the actual referrals our
      specialty pediatric orthopaedic clinic received over a period of 1 month.
      RESULTS: A total of 529 new patient referrals were seen during August 2010. A
      total of 246 (47%) were considered primary care conditions and 283 (53%)
      orthopaedic specialty conditions. The most common primary care condition was a
      nondisplaced phalanx fracture (25/246, 10.1%) and the most common specialty
      condition was a displaced single-bone upper extremity fracture needing reduction
      (36/283, 13%). Only 77 (14.6%) of the total cases met the strict American Academy
      of Pediatrics Surgery Advisory Panel guidelines recommending referral to
      pediatric orthopaedics, with scoliosis being the most frequent condition. For 38
      (7.2%) cases, surgical treatment was required or recommended. Patient age,
      referral source, or type of insurance did not influence whether the condition was
      a primary care or a specialty care case. A total of 134 (25%) cases were referred
      without having an initial diagnosis made by the referring clinician. These
      patients were more likely to have been referred from a primary care practitioner
      than from a tertiary care practitioner whether the diagnosis eventually made was
      considered to be a primary care condition (P=0.03; relative risk, 1.9; 95%
      confidence interval, 96-3.86). CONCLUSIONS: Almost half of all new referrals to a
      tertiary pediatric orthopaedic clinic were for conditions considered to be
      manageable by primary care physicians should they chose to do so. SIGNIFICANCE:
      This has implications for pediatric orthopaedic workforce availability,
      reimbursement under the Affordable Care Act, and pediatric musculoskeletal
      training needs for providers of primary care.

PMID- 22955540
TI  - Evaluating the use of preoperative antibiotics in pediatric orthopaedic surgery.
AB  - PURPOSE OF THE STUDY: To evaluate the rate of infection after minimally invasive
      procedures on a consecutive series of pediatric orthopaedic patients. We
      hypothesized that the use of preoperative antibiotics for minimally invasive
      pediatric orthopaedic procedures does not significantly reduce the incidence of
      surgical site infection requiring surgical debridement within 30 days of the
      primary procedure. METHODS: We retrospectively reviewed 2330 patients having
      undergone minimally invasive orthopaedic procedures at our institution between
      March 2008 and November 2010. Knee arthroscopy, closed reduction with
      percutaneous fixation, soft tissue releases, excision of bony or soft-tissue
      masses, and removal of hardware constituted the vast majority of included
      procedures. Two groups, based on whether prophylactic antibiotics were
      administered before surgery, were created and the incidence of a repeat procedure
      required for deep infection was recorded. Statistical analysis was performed to
      determine significance, if any, between the 2 groups. RESULTS: Chart review of
      the 2330 patients identified 1087 as having received preoperative antibiotics,
      whereas the remaining 1243 patients did not receive antibiotics before surgery.
      Only 1 patient out of the 1243 cases in which antibiotics were not given required
      additional surgery within 30 days of the primary procedure due to a complicated
      surgical site infection (an incidence of 0.0008%). No patients in the antibiotic
      group developed a postoperative infection within 30 days requiring a return to
      the operating room for management. Our data revealed no significant increase in
      the incidence of complicated infection requiring additional procedures when
      antibiotics were not administered before surgery. DISCUSSION: Though prophylactic
      antibiotics have been shown to confer numerous benefits for patients undergoing
      relatively major operations, their use in cases of minimally invasive and/or
      percutaneous orthopaedic surgery is not well defined. Our data suggest that the
      use of prophylactic antibiotics may not be indicated for many less invasive
      procedures when performed in a low-risk pediatric population. Future studies are
      warranted to help establish evidence-based guidelines regarding the routine use
      of prophylactic antibiotics in this specific population, hopefully resulting in
      improved cost-effectiveness and safety while slowing the emergence of new drug
      resistant organisms. LEVEL OF EVIDENCE: Level III, retrospective comparative.

PMID- 22955541
TI  - Preventable childhood injuries.
AB  - BACKGROUND: This is a literature review generated from The Committee on Trauma
      and Prevention of Pediatric Orthopaedic Society of North America to bring to the
      forefront 4 main areas of preventable injuries in children. METHODS: Literature
      review of pertinent published studies or available information of 4 areas of
      childhood injury: trampoline and moonbouncers, skateboards, all-terrain vehicles,
      and lawn mowers. RESULTS: Much literature exists on these injuries. CONCLUSIONS:
      Preventable injuries occur at alarming rates in children. By arming the
      orthopaedist with a concise account of these injuries, patient education and
      child safety may be promoted. LEVEL OF EVIDENCE: 3.

PMID- 22955542
TI  - An unusual cause of paralysis of the peroneal nerve:  a report of 3 cases: 
      retraction.

PMID- 22955543
TI  - Fractures and refractures after femoral locking compression plate fixation in
      children and adolescents.
AB  - BACKGROUND: Locking compression plates (LCPs) are being increasingly utilized in
      fixation of fractures and osteotomies in the pediatric population. However, plate
      insertion or removal may pose a risk of femoral fractures or refractures. The
      goal of this study was to analyze failure patterns associated with LCPs and
      identify possible contributing factors. METHODS: The sample included all patients
      who underwent fixation of femoral fractures or osteotomies utilizing straight
      LCPs at a tertiary pediatric medical center from 2004 to 2009. All were followed
      up until fracture union. The charts and radiographs were reviewed, and data on
      demographics, indications, surgical technique, and timing of plate removal were
      summarized. In cases of failure, the timing, circumstances, fracture location,
      and refixation method were recorded. RESULTS: Thirty-seven patients underwent 41
      straight LCP fixations during the study period. The indication for surgery was
      acute femoral fracture in 25 procedures (25 patients) and elective osteotomy or
      limb lengthening in 16 procedures (12 patients). Thirty-five plates were removed
      after complete clinical and radiographic union. The time from plate fixation to
      removal averaged 13 months (range, 5 to 34 mo) in the fracture group and 17.6
      months (range, 7.5 to 28 mo) in the osteotomy group. Five procedures (12%) were
      complicated by femoral fractures or refractures: 2 occurred after the index
      surgery-1 at the proximal screw and 1 through the original fracture site, with
      plate breakage. Three patients sustained refractures after plate removal, all at
      the original fracture or regenerate site: 1 after a fall and 2 spontaneously. The
      average time from plate removal to refracture was 18 days (range, 10 to 30).
      There were no differences in demographics, timing, or technique between patients
      with and without complications. CONCLUSIONS: Although LCPs are considered
      flexible fixators, they may carry the risk of overstiffness, similar to external
      fixators. Further clinical and biomechanical studies are needed to evaluate risk
      factors for fractures or refractures, particularly in children. There seems to be
      an increase in risk of refracture immediately after plate removal. Caution should
      be taken in the first weeks after plate removal. LEVEL OF EVIDENCE: Level IV.

PMID- 22955544
TI  - Development of a surrogate biomodel for the investigation of clubfoot bracing.
AB  - Congenital talipes equinovarus (clubfoot) is a complex deformity of the lower
      extremity and foot occurring in 1/1000 live births. Regardless of treatment,
      whether conservative or surgical, clubfoot has a stubborn tendency to relapse,
      thus requiring postcorrection bracing. However, to date, there are no
      investigations specifically focused on clubfoot bracing from a bioengineering
      perspective. This study applied engineering principles to clubfoot bracing
      through construction of a surrogate biomodel. The surrogate was developed to
      represent an average 5-year-old human subject capable of biomechanical
      characteristics including joint articulation and kinematics. The components
      include skeleton, articulating joints, muscle-tendon systems, and ligaments. A
      protocol was developed to measure muscle-tendon tension in resting and braced
      positions of the surrogate. Measurement error ranged from 1% to 6% and was
      considered variance due to brace and investigator. In conclusion, this study
      shows that surrogate biomodeling is an accurate and repeatable method to
      investigate clubfoot bracing. The methodology is an effective means to evaluate
      wide ranging brace options and can be used to assist in future brace development
      and the tuning of brace parameters. Such patient-specific brace tuning may also
      lead to advanced braces that increase compliance.

PMID- 22955545
TI  - Postoperative alopecia in children after orthopaedic surgery.
AB  - BACKGROUND: To report the cases of postoperative alopecia encountered after
      orthopaedic surgery at a single-level I trauma pediatric hospital. METHODS: We
      report on 3 children who developed postoperative alopecia after an orthopaedic
      surgery. The chart review included demographics and independent variables
      including age, ethnicity, weight, sex, presence of coexisting medical conditions,
      type and duration of surgery performed, examination findings at presentation and
      diagnosis of alopecia, and outcomes were recorded. Inpatient and outpatient
      clinic notes, operative reports, and recorded vital signs were also reviewed.
      RESULTS: Three children (2 female, 1 male) were noted to develop postoperative
      alopecia. The average age at surgery was 13.7 years (range, 12 to 16). There was
      no significant past medical history, and 2 of 3 patients had obesity as a
      comorbidity. The type of surgery included: 2 proximal femoral osteotomies with
      proximal femoral osteoplasties and 1 wide resection of a congenital tibia
      pseudarthrosis with contralateral vascularized fibular grafting and internal
      fixation. Mean surgical duration was 5.9 hours (range, 4.4 to 7.1), and no
      intraoperative episodes of hypotension (<50 mm Hg) or hypothermia (T<35.9 degrees
      C) occurred. The patients presented 2 to 3 weeks after surgery with hair loss
      localized over the posterior portion of the head. All patients were noted to have
      hair regrowth within 8 to 12 weeks, with 1 patient fully recovered and 2 patients
      continuing hair regrowth at most recent follow-up. CONCLUSIONS: Postoperative
      alopecia is an uncommon but usually self-limited complication that can occur in
      children undergoing orthopaedic surgery. Although rare, the treating physician
      should be aware of its occurrence and course, and appropriate padding of the head
      during surgery is advised. LEVEL OF EVIDENCE: Level IV--retrospective case
      series.

PMID- 22955546
TI  - Complications of ketorolac use in children undergoing operative fracture care.

PMID- 22955547
TI  - Discrimination and anatomical mapping of PET-positive lesions: comparison of CT
      attenuation-corrected PET images with coregistered MR and CT images in the
      abdomen.
AB  - PURPOSE: PET/MR has the potential to become a powerful tool in clinical
      oncological imaging. The purpose of this prospective study was to evaluate the
      performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse
      sequence of the abdomen in comparison with unenhanced low-dose CT images to
      characterize PET-positive lesions. METHODS: A total of 100 oncological patients
      underwent sequential whole-body (18)F-FDG PET with CT-based attenuation
      correction (AC), 40 mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the
      abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by
      CT and MRI with regard to their anatomical location, conspicuity and additional
      relevant information for characterization. RESULTS: From among 66 patients with
      at least one PET-positive lesion, 147 lesions were evaluated. No significant
      difference between MRI and CT was found regarding anatomical lesion localization.
      The MR pulse sequence used performed significantly better than CT regarding
      conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no
      difference was noted for extrahepatic lesions. For overall lesion
      characterization, MRI was considered superior to CT in 40 % of lesions, equal to
      CT in 49 %, and inferior to CT in 11 %. CONCLUSION: Fast Dixon-based T1w MRI
      outperformed low-dose CT in terms of conspicuity and characterization of PET
      positive liver lesions and performed similarly in extrahepatic tumour
      manifestations. Hence, under the assumption that the technical issue of MR AC for
      whole-body PET examinations is solved, in abdominal PET/MR imaging the
      replacement of low-dose CT by a single Dixon-based MR pulse sequence for
      anatomical lesion correlation appears to be valid and robust.

PMID- 22955548
TI  - Substantial genetic overlap between schizotypy and neuroticism: a twin study.
AB  - Schizotypy is phenotypically associated with neuroticism. To reveal the origin of
      this association, we assessed 3,349 (1,449 monozygotic, 1,105 dizygotic [DZ] same
      sex and 795 DZ opposite-sex) twins on a 12-item version of Chapman's Psychosis
      Proneness Scales and the short form of the Eysenck Personality Questionnaire
      Revised as measures of schizotypy and neuroticism. A substantial proportion (0.51
      with 95 % CI from 0.38 to 0.64) of the phenotypic correlation of 0.37 between
      neuroticism and the perceptual and ideational components of schizotypy was
      accounted for by shared genetic influences on these two traits. Moreover, a
      Cholesky decomposition including anhedonia, hypomania and impulsivity fully
      accounted for the heritable variance in perceptual and ideational components of
      schizotypy. These findings suggest a shared genetic etiology between neuroticism
      and perceptual and ideational components of schizotypy and affect future
      investigations on the etiology of these phenotypically overlapping traits and
      affective and psychotic disorders.

PMID- 22955549
TI  - Wie die Mikroben nach Warschau kamen : Wissenstransfer in der Bakteriologie in
      den 1880er Jahren.
AB  - The pathogenic microbe came to be a widely acknowledged "scientific fact" by the
      end of the 19th century. Taking the transfer of bacteriological knowledge to
      Warsaw as an example, this article contributes to understanding the question of
      how knowledge of bacteria was stabilized outside of its original place of
      production. Conceiving bacteriological knowledge as a laboratory practice it
      describes the techniques of mobilizing the "laboratory network" this practice
      depended on. The case of the Polish medical student Odo Bujwid transporting
      Robert Koch's and Louis Pasteur's laboratory networks to Warsaw will be analyzed.
      Bujwid used literary and visual inscriptions to make these laboratory networks
      immutably mobile in Bruno Latour's sense. But he also had to transport three
      dimensional objects central to the networks' functioning back to Warsaw. Personal
      exchange was, furthermore, essential to their successful transportation to the
      Polish kingdom. Next to Bujwid's efforts to transform the laboratory networks
      into immutable mobiles, the analysis will extend the focus to mutable mobiles as
      well and will thus show that the successful stabilization of bacteriological
      knowledge in Warsaw was due not only to the immutability of its laboratory
      network but to its flexibility and elasticity as well.

PMID- 22955550
TI  - Interactions with DOM and biofilms affect the fate and bioavailability of
      insecticides to invertebrate grazers.
AB  - We studied the fate and bioavailability of insecticides in short-term experiments
      (48 h) with different hydrophobicity (3.8 pM carbofuran, 3.0 pM lindane, and 5.3
      pM chlorpyrifos) across gradients in dissolved organic matter (low-, medium-, and
      high-DOM) in freshwater microcosms, mimicking runoff events of pesticides. The
      effects of biofilms were studied by including treatments with biofilms cultivated
      under different DOM-concentrations. The presence of biofilms negatively affected
      chlorpyrifos water concentrations, indicating rapid sorption of this hydrophobic
      pesticide, while lindane concentrations instead increased and carbofuran
      concentrations were unaffected. Associations of lindane and chlorpyrifos with
      biofilms were 1.6-2.0 times higher in low- and high-DOM than in medium-DOM
      treatments, indicating that sorption was affected not only by the quantity, but
      also by the quality of DOM. Although the proportion of pesticides recovered in
      biofilms was consistently less than 1 % of added pesticide, pesticide
      concentrations in biofilms were on average more than 75- (carbofuran) and 382
      times (lindane) higher than those in water. Snail accumulation of all three
      pesticides was significantly affected by DOM-concentrations and correlated to
      pesticide hydrophobicity, but the relationships were not straightforward. For
      example, carbofuran uptake in treatments without biofilms was higher in low-DOM
      than in medium- and high-DOM treatments, while chlorpyrifos uptake instead
      increased across the DOM-gradient. Biofilms played a role only for the uptake of
      chlorpyrifos, which decreased markedly in the presence of biofilms.
      Bioconcentration factors (BCF) calculated for snails and biofilms differed for
      the three pesticides and were related to their sorption behaviour (i.e.,
      hydrophobicity). The relative proportion of pesticide uptake through biofilm
      consumption was consistently less than 2 %, showing that passive uptake was by
      far the predominant uptake pathway for all three pesticides.

PMID- 22955551
TI  - New EVAR devices: pros and cons.
AB  - The first randomized controlled trials comparing the two procedures (EVAR versus
      open repair) for the treatment of abdominal aortic aneurysms showed considerably
      better short-term outcomes and on the other side higher rates of device
      associated reinterventions and remarkable financial burden in the endovascular
      arm. In the meantime, specialists experience and expertise have been improved
      significantly. To solve the reported drawbacks and to prevent endografts
      associated complications, safer fixation features, lower profile, more flexible
      design and new revolutionary release and deployment mechanisms of stent-grafts
      have been also developed and established over the last years. In this review, we
      present the new EVAR devices and attempt to provide an overview of their
      premature performance based on the literature and the clinical practice in our
      institution.

PMID- 22955552
TI  - The use of the AnacondaTM stent graft for abdominal aortic aneurysms.
AB  - The AnacondaTM is a modular bifurcated stent-graft of woven polyester and nitinol
      ring stents that has been commercially available since 2005. It was the first
      truly repositionable stent-graft and features a magnet wire contralateral limb
      cannulation system. It has excellent fixation and sealing properties and its ring
      stent construction results in it being highly conformable and therefore
      applicable in angulated and tortuous anatomy.

PMID- 22955553
TI  - The use of Endurant stent-graft for abdominal aortic aneurysm: the story about
      extension of instruction for use with persistent good results of stent-graft
      latest generation.
AB  - The Endurant stent-graft (Medtronic, Inc., Minneapolis, MN, USA) is a latest
      generation device for the treatment of abdominal aortic aneurysm. The idea behind
      designing such a graft came from the intention to broad the instruction for use
      (IFU) and to enable it to treat more challenging anatomy including the 10mm neck
      lengths, and more severe suprarenal and infrarenal angulations. Endurant stent
      graft has active fixation through suprarenal stent with anchoring pins to provide
      migration resistance, optimized heights of stents and spacing between them for
      improved flexibility and conformability, low-profile delivery system with
      hydrophilic coating and controlled simple deployment mechanism. Short term
      results are excellent. Technical and clinical success is confirmed in Regulatory
      trials (EU and USA), as well as in ENGAGE and the Canadian registry. Many current
      publications record the use of Endurant stent-graft outside the Instruction for
      use. The results in a group of patients outside the instruction for use are
      comparable to those within instruction for use; with the exception of
      perioperative proximal endoleak type I. Mid-term results are consistent with
      short-term results. The long-term results are lacking.

PMID- 22955554
TI  - The Bolton Treovance abdominal stent-graft: European clinical trial design.
AB  - Endovascular aortic repair (EVAR) has emerged as a promising, less invasive
      alternative to conventional open surgery for the treatment of infrarenal
      abdominal aortic aneurysms (AAAs). In the last 20 years, the application rate of
      EVAR and its clinical results have significantly improved thanks to the evolution
      of stent-grafts and endovascular delivery systems. However, further development
      is still needed to reduce the incidence of complications and secondary re
      interventions. The Treovance abdominal aortic stent-graft (Bolton Medical,
      Barcelona, Spain) is a new-generation endovascular device, developed to increase
      flexibility, lower profile, improve deployment and sealing mechanisms. In
      particular, it is provided with some innovative features as a double layer of
      proximal barbs (suprarenal and infrarenal) for supplemental fixation, dull barbs
      between modules to avoid potential leg disconnections, detachable outer sheath
      provided with a new-design hemostatic valve, and a double improved mechanism
      (slow motion and "pin and pull") for precise stent-graft deployment. A European
      prospective, non-randomized, multi-institutional, "first-in-human" trial (the
      ADVANCE trial) was conducted from March to December 2011 to assess the safety and
      performance of the Treovance stent-graft system before commercialization. Thirty
      patients with anatomically suitable non-ruptured AAAs were enrolled at five
      clinical sites in Italy, Spain, and Germany. EVAR was completed successfully in
      all patients. The stent-graft was delivered and deployed safely even in heavily
      angulated or calcified anatomies. No 30-day device-related complications nor
      deaths were observed. Preliminary experience with the Treovance abdominal stent
      graft within the ADVANCE trial was satisfactory with regard to technical success
      and perioperative clinical results. Follow-up data are needed to assess mid- and
      long-term clinical outcomes, along with durability of this new-generation
      endovascular device.

PMID- 22955555
TI  - Body of knowledge around the diabetic foot and limb salvage.
AB  - Body of knowledge around the There has been considerable progress in the care of
      the diabetic foot over the last three decades. The development of
      multidisciplinary diabetic foot care has provided specialist management of the
      neuropathic foot and the neuroischemic foot. Significant progress has been made
      in the treatment of both of these entities. The crucial aspects of therapy are
      the treatment of infection, relief of ischemia and promotion of wound healing.
      The multidisciplinary, hospital-based diabetic foot clinic has proved to be a
      successful way of reducing amputations and improving outcomes. This review
      summarises the major advances in the care of the diabetic neuroischaemic foot.
      These have greatly improved the outlook and prognosis for diabetic patients with
      ischemic foot problems.

PMID- 22955556
TI  - Endovascular preservation of pelvic circulation with external iliac-to-internal
      iliac artery "cross-stenting" in patients with aorto-iliac aneurysms: a case
      report and literature review.
AB  - Endovascular success depends heavily upon anatomical suitability for secure graft
      placement. Common iliac artery (CIA) aneurysms frequently extend close to the
      iliac bifurcation, requiring distal fixation in the external iliac artery (EIA),
      in turn excluding the internal iliac artery (IIA). The preservation of
      circulation to at least one IIA artery is highly recommended. We report an
      endovascular technique for complete preservation of the hypogastric arteries of
      an aorto-iliac aneurysm extending into the iliac bifurcation and hypogastric
      artery. A left CIA aneurysm involving the iliac bifurcation was excluded with a
      covered Fluency stent-graft (Bard Inc., New Jersey, USA) deployed from the EIA
      into the IIA followed by the internal deployment of a Luminex uncovered stent
      (Bard Inc.) extended into one branch of the hypograstric artery. IVUS evaluation
      was essential in determining precise aneurysm and sealing zone measurements.
      Complete preservation of hypogastric circulation was achieved. The placement of
      the uncovered stent effectively extended the sealing zones without covering
      either of the hypogastric distal branches and concurrently corrected the Fluency
      stent kinking due to severe arterial tortuosity. In CIA aneurysms involving the
      IIA, an uncovered stent can extend the sealing zones, whilst maintaining complete
      preservation of pelvic circulation and offers support to the covered stent-graft.
      IVUS seems necessary for precise neck evaluation.

PMID- 22955557
TI  - Long-term survival (>20 years) following heart transplantation.
AB  - AIM: Only a few papers with patients surviving more than 15 years after heart
      transplantation have been reported. Herein we report the characteristics of
      patients transplanted between 1984 and 1989 who are long-term survivors (>20
      years). Survival after transplant, recipient and donor age and aetiology of heart
      failure were also compared with patients transplanted in the decades 1990-1999
      and 2000-2009. METHODS: Our Heart Transplant Program Database and medical records
      of all cardiac transplants performed in our centre from July 1984 to 1989 were
      reviewed. Primary endpoint of the study was the long-term survival and secondary
      end points were the incidence of transplant-related complications over time.
      RESULTS: Forty-five transplants were performed in 1984-1989, 41 patients were
      male, median age was 46 years (IQR: 39-55), median donor age was 24 years (19-29)
      and mean graft ischemic time was 134+/-64 minutes. The actuarial survival of this
      cohort was 77.8%, 64.4%, 48.9%, 35.6% and 24.2% at 1, 5, 10, 15 and 20 years,
      respectively. Univariate Cox regression analysis revealed the female gender, the
      graft ischemic time, the recipient-donor gender mismatch, a diagnosis of diabetes
      and the number of acute rejection episodes during the first year post-transplant
      as significant risk factors adversely affecting long-term survival. Cardiac
      allograft vasculopathy is the main cause of death. The mean recipient and donor
      age and the graft ischemic time have progressively increased over time but
      survival has not changed. CONCLUSION: The long-term outcome of heart
      transplantation is noteworthy. The main limiting factor for survival is the
      allograft vasculopathy. Considering the tremendous advances in the
      immunosuppressive therapy and in the understanding of CAV pathophisyology, we can
      hope for even better results in the next years.

PMID- 22955558
TI  - Physical activity of patients undergoing isolated or combined aortic valve
      replacement.

PMID- 22955559
TI  - Segmental hair analysis and estimation of methamphetamine use pattern.
AB  - The aim of this study was to investigate whether the results of segmental hair
      analysis can be used to estimate patterns of methamphetamine (MA) use. Segmental
      hair analysis for MA and amphetamine (AP) was performed. Hair was cut into the
      hair root, consecutive 1 cm length segments and 1-4 cm length segments. Whole
      hair was also analyzed. The hair samples were incubated for 20 h in 1 mL methanol
      containing 1 % hydrochloric acid after washing the hair samples. Hair extracts
      were evaporated and derivatization was performed using trifluoroacetic anhydride
      in ethylacetate at 65  degrees C for 30 min. Derivatized extract was analyzed by
      gas chromatography/mass spectrometry. The 15 subjects consisted of 13 males and
      two females and their ages ranged from 25 to 42 (mean, 32). MA and AP
      concentrations in the whole hair ranged from 3.00 to 105.10 ng/mg (mean, 34.53)
      and from 0.05 to 4.76 ng/mg (mean, 2.42), respectively. Based on the analysis of
      the 1 cm length segmental hair, the results were interpreted in a way to
      distinguish between continuous use of MA (n = 10), no recent but previous use of
      MA (n = 3), and recent but no previous use of MA (n = 2). Furthermore, the
      individuals were interpreted as light, moderate, and heavy users based on
      concentration ranges previously published.

PMID- 22955561
TI  - Intraoperative management of tracheobronchial rupture after double-lumen tube
      intubation.
AB  - PURPOSE: Tracheobronchial rupture is an uncommon but potentially serious
      complication of endotracheal intubation. In this study, the diagnosis and
      treatment strategies of a specific group of ruptures caused by double-lumen tube
      intubation are herein presented. METHODS: The medical records of 18 patients
      diagnosed and treated for tracheobronchial rupture after undergoing double-lumen
      tube intubation between January 1999 and October 2010 are analyzed
      retrospectively. RESULTS: In all cases, the ruptures occurred in the membranous
      portion. The average length of laceration was 2.44 +/- 1.78 cm. The most common
      site of rupture was in the lower third of the trachea (n = 7, 39 %) or the left
      mainstem bronchus (n = 7, 39 %). One patient was diagnosed before incision using
      fiberoptic bronchoscopy, and 17 patients were diagnosed using direct vision of
      the rupture intraoperatively. All patients were treated successfully with
      surgery. There were no morbidities or mortalities recorded in relation to
      tracheobronchial rupture. CONCLUSIONS: Thoracic surgeons must be alerted to the
      possibility for tracheobronchial rupture in patients intubated with double-lumen
      tubes, a procedure commonly used in thoracic surgery. Immediate repair must be
      performed for any laceration diagnosed intraoperatively.

PMID- 22955562
TI  - Contribution of SATB2 to the stronger osteogenic potential of bone marrow stromal
      cells from craniofacial bones.
AB  - Previous studies have shown that craniofacial bone marrow stromal cells (BMSCs)
      have a strong osteogenic potential. However, the mechanism by which BMSCs of
      various embryonic origins develop diverse osteogenic potentials remains unclear.
      To investigate the mechanisms regulating osteoblast differentiation in two
      different types of BMSCs, we compared the temporal and spatial mRNA and protein
      expression patterns of Satb2 and its downstream gene Hoxa2 by using real-time
      polymerase chain reaction, Western blotting and fluorescent immunostaining in
      mandible BMSCs (M-BMSCs) and tibia BMSCs (T-BMSCs) undergoing osteoblast
      differentiation. Higher levels of alkaline phosphatase, greater calcium
      accumulation and earlier expression of Runx2 were observed in osteogenic-induced
      M-BMSCs compared with T-BMSCs. Low levels of Satb2 were detected in both types of
      uninduced BMSCs but the majority of SATB2 was located in the nuclei of M-BMSCs.
      Notably, Satb2 was expressed earlier in M-BMSCs and Hoxa2, a downstream target of
      Satb2, was not expressed in uninduced M-BMSCs or during osteoblast
      differentiation, just as during embryonic mandible development. In contrast,
      Hoxa2 was reactivated in T-BMSCs during osteoblast differentiation. Based on
      these results, we conclude that SATB2 plays a different role during osteoblast
      differentiation of M-BMSCs and T-BMSCs. The earlier activation of Satb2
      expression in M-BMSCs compared with T-BMSCs might explain the stronger osteogenic
      potential of M-BMSCs.

PMID- 22955563
TI  - Prevascularization of self-organizing engineered heart tissue by human umbilical
      vein endothelial cells abrogates contractile performance.
AB  - Establishing vascularization is a critical obstacle to the generation of
      engineered heart tissue (EHT) of substantial thickness. Addition of endothelial
      cells to the formative stages of EHT has been demonstrated to result in
      prevascularization, or the formation of capillary-like structures. The detailed
      study of the effects of prevascularization on EHT contractile function is
      lacking. Here, we evaluated the functional impact of prevascularization by human
      umbilical vein endothelial cells (HUVECs) in self-organizing EHT. EHT fibers were
      generated by the self-organization of neonatal rat cardiac cells on a fibrin
      hydrogel scaffold with or without HUVECs. Contractile function was measured and
      force-length relationship and rate of force production were assessed.
      Immunofluorescent studies were used to evaluate arrangement and distribution of
      HUVECs within the EHT fibers. RT-PCR was used to assess the transcript levels of
      hypoxia inducible factor-1a (Hif-1alpha). EHT with HUVECs manifested tubule-like
      structures at the periphery during fiber formation. After fiber formation, HUVECs
      were heterogeneously located throughout the EHT fiber and human CD31+ tubule-like
      structures were identified. The expression level of Hif-1alpha did not change
      with the addition of HUVECs. However, maximal force and rate of force generation
      were not improved in HUVECs containing EHT as compared to control EHT fibers. The
      addition of HUVECs may result in sparse microvascularization of EHT. However,
      this perceived benefit is overshadowed by a significant decrease in contractile
      function and highlights the need for perfused vascularization strategies in order
      to generate EHT that approaches clinically relevant dimensions.

PMID- 22955564
TI  - Local substitution of GDF-15 improves axonal and sensory recovery after
      peripheral nerve injury.
AB  - The growth/differentiation factor-15, GDF-15, has been found to be secreted by
      Schwann cells in the lesioned peripheral nervous system. To investigate whether
      GDF-15 plays a role in peripheral nerve regeneration, we substituted exogenous
      GDF-15 into 10-mm sciatic nerve gaps in adult rats and compared functional and
      morphological regeneration to a vehicle control group. Over a period of 11 weeks,
      multiple functional assessments, including evaluation of pinch reflexes, the
      Static Sciatic Index and of electrophysiological parameters, were performed.
      Regenerated nerves were then morphometrically analyzed for the number and quality
      of regenerated myelinated axons. Substitution of GDF-15 significantly accelerated
      sensory recovery while the effects on motor recovery were less strong. Although
      the number of regenerated myelinated axons was significantly reduced after GDF-15
      treatment, the regenerated axons displayed advanced maturation corroborating the
      results of the functional assessments. Our results suggest that GDF-15 is
      involved in the complex orchestration of peripheral nerve regeneration after
      lesion.

PMID- 22955565
TI  - A phenomenological theory of nonphotochemical laser induced nucleation.
AB  - We present a theory of electric field driven phase transitions that occur via
      nucleation of needle-shaped, metallic particles. The predictions of this theory
      have much in common with the observations related to nonphotochemical laser
      induced nucleation (NPLIN). That connection is rather paradoxical because the
      final NPLIN products are dielectric crystals. By elaborating on the unique
      features of field induced transitions and the complexities of liquid systems, we
      discuss how our theory may provide some insight into the open question of the
      NPLIN mechanism. A qualitative description of the post nucleation stage and
      conjectures about the microscopic nature of the metallic particles in liquids are
      also provided.

PMID- 22955566
TI  - Hernioscopy is a good option in strangulated inguinal hernias that retract under
      general anesthesia.

PMID- 22955567
TI  - Nicotine differentially modulates antisaccade eye-gaze away from emotional
      stimuli in nonsmokers stratified by pre-task baseline performance.
AB  - RATIONALE AND OBJECTIVE: Studies indicate that nicotine enhances some aspects of
      attention and executive functioning and attenuates the attentional salience of
      emotionally negative distractors. The purpose of this study was to assess whether
      nicotine can enhance executive control over prepotent responses in emotional
      contexts in nonsmokers and whether such enhancement is greater in individuals
      with low baseline performance (BP). METHODS: The antisaccade task (AST) measures
      the inhibition of the tendency to glance in the direction of the onset of a
      visual stimulus and thus is an index of control over prepotent responses. Ten
      male and 14 female nonsmokers wore nicotine and placebo patches on
      counterbalanced days that included emotional picture primes and targets. RESULTS:
      There were significant beneficial effects of nicotine on antisaccade reaction
      time (RT). These beneficial effects occurred in individuals with poor and average
      BP, but not in high baseline performers. In slow baseline RT individuals,
      nicotine reduced RTs associated with negative targets in the left visual field
      (VF) and reduced RTs associated with positive and neutral targets in the right
      VF. In contrast, in the average baseline group, nicotine reduced RTs for positive
      targets in both VFs and neutral targets in the left VF. CONCLUSIONS: The results
      suggest that nicotine may produce its effects by enhancing executive functions
      and that the differential effects as a function of VF, target emotion, and group
      may also reflect lateralized differences in the effects of nicotine on brain
      reactivity to emotional stimuli.

PMID- 22955568
TI  - Interactive effects of methylphenidate and alcohol on discrimination, conditioned
      place preference and motor coordination in C57BL/6J mice.
AB  - INTRODUCTION: Prior research indicates methylphenidate (MPH) and alcohol
      (ethanol, EtOH) interact to significantly affect responses humans and mice. The
      present studies tested the hypothesis that MPH and EtOH interact to potentiate
      ethanol-related behaviors in mice. METHODS: We used several behavioral tasks
      including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned
      place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas
      chromatographic methods to measure brain tissue levels of EtOH and the D- and L
      isomers of MPH and the metabolite, ethylphenidate (EPH). RESULTS: In
      discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH
      generalization curve (1-2 mg/kg) for MPH-trained mice, but no effects of MPH
      (0.625-1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5 g/kg) were
      observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination
      significantly increased time on the drug paired side compared to vehicle (30.7
      %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors
      measured in a parallel rod apparatus indicated that the drug combination was very
      ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH
      concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH.
      However, EtOH significantly increased D-MPH and L-EPH without changing L-MPH
      brain concentrations. CONCLUSIONS: The enhanced behavioral effects when EtOH is
      combined with MPH are likely due to the selective increase in brain D-MPH
      concentrations. These studies are consistent with observations in humans of
      increased interoceptive awareness of the drug combination and provide new
      clinical perspectives regarding enhanced ataxic effects of this drug combination.

PMID- 22955570
TI  - Measuring and modeling patient-specific distributions of material properties in
      abdominal aortic aneurysm wall.
AB  - Both the clinically established diameter criterion and novel approaches of
      computational finite element (FE) analyses for rupture risk stratification of
      abdominal aortic aneurysms (AAA) are based on assumptions of population-averaged,
      uniform material properties for the AAA wall. The presence of inter-patient and
      intra-patient variations in material properties is known, but has so far not been
      addressed sufficiently. In order to enable the preoperative estimation of patient
      specific AAA wall properties in the future, we investigated the relationship
      between non-invasively assessable clinical parameters and experimentally measured
      AAA wall properties. We harvested n = 163 AAA wall specimens (n = 50 patients)
      during open surgery and recorded the exact excision sites. Specimens were tested
      for their thickness, elastic properties, and failure loads using uniaxial tensile
      tests. In addition, 43 non-invasively assessable patient-specific or specimen
      specific parameters were obtained from recordings made during surgery and patient
      charts. Experimental results were correlated with the non-invasively assessable
      parameters and simple regression models were created to mathematically describe
      the relationships. Wall thickness was most significantly correlated with the
      metabolic activity at the excision site assessed by PET/CT (rho = 0.499, P = 4 *
      10(-7)) and to thrombocyte counts from laboratory blood analyses (rho = 0.445, P
      = 3 * 10(-9)). Wall thickness was increased in patients suffering from diabetes
      mellitus, while it was significantly thinner in patients suffering from chronic
      kidney disease (CKD). Elastic AAA wall properties had significant correlations
      with the metabolic activity at the excision site (PET/CT), with existent
      calcifications, and with the diameter of the non-dilated aorta proximal to the
      AAA. Failure properties (wall strength and failure tension) had correlations with
      the patient's medical history and with results from laboratory blood analyses.
      Interestingly, AAA wall failure tension was significantly reduced for patients
      with CKD and elevated blood levels of potassium and urea, respectively, both of
      which are associated with kidney disease. This study is a first step to a future
      preoperative estimation of AAA wall properties. Results can be conveyed to both
      the diameter criterion and FE analyses to refine rupture risk prediction. The
      fact that AAA wall from patients suffering from CKD featured reduced failure
      tension implies an increased AAA rupture risk for this patient group at
      comparably smaller AAA diameters. 

PMID- 22955571
TI  - Sensitive and selective SERS probe for trivalent chromium detection using citrate
      attached gold nanoparticles.
AB  - In this article, we have demonstrated a sensitive and selective surface enhanced
      Raman spectroscopy (SERS) probe, based on citrate-capped gold nanoparticles
      (AuNPs), for trivalent chromium (Cr(3+)) detection. After introducing Tween 20 to
      a solution of citrate-capped AuNPs, the as-prepared Tween 20/citrate-AuNP probe
      could recognize Cr(3+) at a 50 * 10(-9) M level in an aqueous medium at a pH of
      6.0. Tween 20 can stabilize the citrate-capped AuNPs against conditions of high
      ionic strength. Due to the chelation between Cr(3+) and citrate ions, AuNPs
      undergo aggregation. As a result, it formed several hot spots and provided a
      significant enhancement of the Raman signal intensity through electromagnetic
      (EM) field enhancements. A detailed mechanism for tremendous SERS intensity
      change had been discussed. The selectivity of this system toward Cr(3+) was 400
      fold, remarkably greater than other metal ions.

PMID- 22955572
TI  - Exercise training in intermittent claudication: effects on antioxidant genes,
      inflammatory mediators and proangiogenic progenitor cells.
AB  - Exercise training remains a therapy of choice in intermittent claudication (IC).
      However, too exhaustive exercise may cause ischaemic injury and inflammatory
      response. We tested the impact of three-month treadmill training and single
      treadmill exercise on antioxidant gene expressions, cytokine concentrations and
      number of marrow-derived proangiogenic progenitor cells (PPC) in the blood of IC
      patients. Blood samples of 12 patients were collected before and after training,
      before and 1, 3 and 6 hours after the single exercise. PPCs were analysed with
      flow cytometry, cytokine concentrations were checked with Milliplex MAP, while
      expression of mRNAs and miRNAs was evaluated with qRT-PCR. Treadmill training
      improved pain-free walking time (from 144 +/- 44 seconds [s] to 311 +/- 134 s,
      p=0.02) and maximum walking time (from 578 +/- 293 s to 859 +/- 423 s, p=0.01) in
      IC patients. Before, but not after training, the single treadmill exercise
      increased the number of circulating CD45dimCD34+CD133-KDR+ PPCs (p=0.048),
      decreased expression of  HMOX1  (p=0.04) in circulating leukocytes, reduced
      tumour necrosis factor-alpha (p=0.03) and tended to elevate myeloperoxidase
      (p=0.06) concentrations in plasma. In contrast, total plasminogen activator
      inhibitor-1 was decreased by single exercise only after, but not before training
      (p=0.02). Both before and after training the single exercise decreased monocyte
      chemoattractant protein (MCP)-1 (p=0.006 and p=0.03) concentration and increased 
      SOD1  (p=0.001 and p=0.01) expression. Patients after training had also less
      interleukin-6 (p=0.03), but more MCP-1 (p=0.04) in the blood. In conclusion,
      treadmill training improves walking performance of IC patients, attenuates the
      single exercise-induced changes in gene expressions or PPC mobilisation, but may
      also lead to higher production of some proinflammatory cytokines.

PMID- 22955573
TI  - Continuous-flow biomolecule concentration and detection in a slanted nanofilter
      array.
AB  - We demonstrate continuous-flow biomolecule concentration and detection in a
      microfabricated slanted sieving structure, which we term a herringbone nanofilter
      array (HNA). The HNA structure consists of periodically-patterned deep and
      shallow nanoslits meeting at right angles. In addition to concentration, we can
      discriminate different sized analytes by mixing a fluorescent probe with the
      sample and measuring the extent of the concentrating effect. Using this
      principle, we interrogate biomolecular interactions, including protein-DNA
      binding, protein-protein interaction and antibody-antigen binding. The final
      example demonstrates a novel method to perform a homogeneous immunoassay for
      detecting a disease marker, human C-reactive protein (CRP), using fluorescent
      labeled antibodies at clinically relevant concentrations. The signal
      amplification potential and continuous flow operation provide a significant
      advantage over other microfluidic batch separation techniques for the easy
      integration of this device into a common point-of-care diagnostic platform.

PMID- 22955574
TI  - Radiation exposure should not limit bone scintigraphy with 18F-NaF.

PMID- 22955575
TI  - New findings on the underlying neural mechanism of emotion induced by frightening
      music.

PMID- 22955569
TI  - Emotional valence and context of social influences on drug abuse-related behavior
      in animal models of social stress and prosocial interaction.
AB  - RATIONALE: Social factors are important determinants of drug dependence and
      relapse. OBJECTIVES: We reviewed pre-clinical literature examining the role of
      social experiences from early life through the development of drug dependence and
      relapse, emphasizing two aspects of these experiences: (1) whether the social
      interaction is appetitive or aversive and (2) whether the social interaction
      occurs within or outside of the drug-taking context. METHODS: The models reviewed
      include neonatal care, isolation, social defeat, chronic subordination, and
      prosocial interactions. We review results from these models in regard to effects
      on self-administration and conditioned place preference established with alcohol,
      psychostimulants, and opiates. RESULTS: We suggest that in general, when the
      interactions occur outside of the drug-taking context, prosocial interactions are
      protective against drug abuse-related behaviors, whereas social stressors
      facilitate these behaviors. By contrast, positive or negative social interactions
      occurring within the drug-taking context may interact with other risk factors to
      enhance or inhibit these behaviors. CONCLUSIONS: Despite differences in the
      nature and complexity of human social behavior compared to other species, the
      evolving animal literature provides useful models for understanding social
      influences on drug abuse-related behavior that will allow for research on the
      behavioral and biological mechanisms involved. The models have contributed to
      understanding social influences on initiation and maintenance of drug use, but
      more research is needed to understand social influences on drug relapse.

PMID- 22955576
TI  - Therapeutic changes in the occlusal plane inclination using intermaxillary
      elastics.
AB  - AIM: The goal of the study was the evaluation of opposing intermaxillary elastics
      concerning potential change in the occlusal plane inclination relative to
      relevant vertical structures. PATIENTS AND METHODS: Thirty-two late adolescent,
      skeletally homogeneous patients (basal-sagittal relationship: neutral; basal
      vertical: neutral; no transverse discrepancies) were treated either with Class II
      (group A; n=16) or Class III elastics (group B; n=16) for unimaxillary space
      closure. Mean wearing times were 26 (A) and 24 months (B). Cephalograms at the
      start and end of treatment were analyzed. Changes in the inclination of the
      occlusal plane (BOP according to Downs) relative to three reference planes (NL,
      ML, NSL), as well as changes in the reference planes toward each other underwent
      statistical testing with a two-tailed Student t-test. RESULTS: The occlusal plane
      shift differed significantly when opposing elastics were applied (p<0.001). The
      induced shift with Class II elastics (A) was clockwise, while Class III elastics
      were counterclockwise (A: NL-BOP: +0.9 degrees , ML-BOP: -2.1 degrees ; B: NL
      BOP: -3.1 degrees , ML-BOP: +3 degrees ). Reference planes NL and ML underwent
      insignificant change towards one another (A: -1.2 degrees ; B: -0.1 degrees ).
      The maxillo-mandibular complex itself rotated counterclockwise toward the
      anterior cranial base (NSL) (A: NL-NSL: -0.8 degrees , ML-NSL: -2 degrees ; B: NL
      NSL: -0.6 degrees , ML-NSL: -0.7 degrees ). Thus, almost no change in BOP (+0.1
      degrees , n.s.) relative to NSL was detected when Class II elastics were applied,
      whereas the use of Class III elastics led to a significant counterclockwise
      rotation (-3.7 degrees , p<0.001) CONCLUSION: Class III elastics enhance the
      physiologic inclination of the maxillo-mandibular complex at the level of the
      occlusal plane, whereas Class II elastics oppose or even eliminate the process.

PMID- 22955577
TI  - IL-1beta and compressive forces lead to a significant induction of RANKL
      expression in primary human cementoblasts.
AB  - AIM: The aim of this study was to investigate the response of primary human
      cementoblasts to conditions as they occur on the pressure side during orthodontic
      tooth movement. METHODS: In our previous study, the cementoblasts were
      characterized using markers for osteoblastogenic differentiation and the
      cementoblast-specific marker CEMP-1. Initially, primary human cementoblasts were
      compressed for 1 h, 4 h, and 6 h (30 g/cm(2)). In the second experiment, the
      cementoblasts were stimulated with interleukin (IL)-1beta for 24 h and for 96 h
      with 1 ng/ml and 10 ng/ml and subsequently compressed for 1 h and 6 h. Changes in
      mRNA expression for receptor activator of NF-kappaB (RANK), RANK ligand (RANKL),
      osteoprotegerin (OPG), and cyclooxygenase-2 (COX-2) were measured by quantitative
      real-time polymerase chain reaction (RT-PCR). RANK and RANKL were also examined
      by immunocytochemical staining at the protein level. RESULTS: Compression (30
      g/cm(2)) led to a significant increase in RANKL expression after 6 h. OPG
      expression in compressed cementoblasts was significantly reduced after 1 h. RANK
      remained unchanged during the course of the experiment. Stimulation with IL-1beta
      induced RANKL and OPG expression. However, IL-1beta-dependent induction of RANKL
      was more prominent than the induction of OPG, leading to a (significant) increase
      in the RANKL/OPG ratios. The expression of RANK remained unchanged after 24 h of
      stimulation with IL-1beta and decreased significantly after 96 h. Compression of
      the prestimulated cells resulted in a further increase in RANKL expression
      significant after 6 h. OPG and RANK expression remained unchanged compared to the
      unstimulated sample. COX-2 increased significantly after both compression and
      stimulation with IL-1beta. Combined stimulation and compression resulted in a
      significant further increase after 6 h compared to IL-1beta stimulation alone.
      CONCLUSION: Primary human cementoblasts in vitro express increased levels of
      RANKL, in particular during the combination of inflammation and compression. The
      increase in RANKL expression is not compensated by an increase in OPG expression.
      The induction of RANKL expression was associated with a significant increase in
      COX-2 expression. Since RANKL attracts osteoclasts, its increase might be
      associated with the progression of root resorption. The in vitro alterations in
      cementoblasts we observed may be indicators of cellular mechanisms that lead to
      the increased root resorption during orthodontic treatment.

PMID- 22955579
TI  - Intravascular stenting to treat left hepatic vein stenosis following extended
      right hepatectomy.

PMID- 22955578
TI  - Retrospective investigation of gingival invaginations: Part II: microbiological
      findings and genetic risk profile.
AB  - BACKGROUND AND OBJECTIVE: Gingival invaginations are a frequent finding during
      tooth extraction and following orthodontic space closure. Based on the
      interdental localization and sometimes pronounced depth, it has been suggested
      that a gingival invagination may impede oral hygiene. In Part I of this series,
      the time until active tooth movement and the localization of extraction were
      identified as potential risk factors for the development of gingival
      invagination. The aims of the present study were the analysis of the microbial
      spectrum of a gingival invagination in comparison with pool samples of the sulcus
      of Ramfjord teeth, on the one hand, and the importance of genetic variations of
      the pro-inflammatory mediator interleukin-1 (IL-1) and its receptor antagonist
      (IL-1-RN), on the other hand. In addition, a possible role of smoking as a risk
      factor was evaluated. SUBJECTS AND METHODS: A total of 30 patients with (n=16)
      and without (n=14) gingival invagination were examined for the presence of eleven
      periodontal pathogen bacterial species with a commercially available test (micro
      IDent(r)Plus, Hain Lifescience, Nehren, Germany). The genetic evaluation was
      performed with the GenoType(r) IL-1 test (Hain Lifescience). RESULTS: The results
      of the microbiological analysis of gingival invaginations showed that the
      bacterial flora might differ or even be higher than the pool sample from sulcus
      regions. The genetic evaluation demonstrated that in the group without gingival
      invagination only 14% showed an IL-1 polymorphism, whereas this value was twice
      as high (35%) in the group with gingival invagination. In addition, a combination
      of both polymorphisms IL-1 and IL-1-RN was only found in patients with gingival
      invagination (25%). Interestingly, smoking patients showed a significant increase
      of the severity of the gingival invagination. CONCLUSION: This retrospective
      study demonstrated that gingival invagination might be accompanied with an
      altered microbiological bacterial spectrum and a genetic IL-1 polymorphism. In
      addition, smoking was identified as another potential risk factor for the
      severity of gingival invaginations.

PMID- 22955580
TI  - "SR stress" in mixed hindlimb muscles of aging male rats.
AB  - Impaired sarcoplasmic reticulum (SR) function has been associated with reduced
      muscle force generation and locomotor function in aging animals. This study was
      conducted to determine the extent to which aging increased SR stress markers in
      male rats, and the extent to which volitional exercise affected them. We
      harvested medial gastrocnemius muscles from F344/BN rats that were adult (8
      months; n = 8), aging (24 months; n = 8) and that aged with wheel access for 16
      months (24 months; n = 4). SR calcium handling assays and immunoblotting (Caspase
      12, dysferlin and LC3) were performed on crude homogenates and SR-enriched
      microsomal fractions. Aging was associated with increased Caspase 12 and SR
      dysferlin, as well as a reduced LC3II/I ratio and impaired calcium release.
      Despite further increases in Caspase 12, voluntary wheel running partially
      restored SR calcium release and dysferlin toward younger levels. Of note, the
      LC3II/I was also partially restored in the voluntary wheel running group,
      suggesting increased autophagy. These results suggest that impaired SR function
      with aging is associated with age-related increases in SR stress, possibly
      related to reduced autophagy. Long-term volitional exercise improved SR function
      and markers of autophagy, despite increased Caspase 12, suggesting that running
      contributed a beneficial stress that differed from the "distress" of sedentary
      aging.

PMID- 22955581
TI  - Accountable and transparent.

PMID- 22955583
TI  - Moonlight drive.

PMID- 22955582
TI  - Spinning threads.

PMID- 22955594
TI  - Policy: Rethink chemical risk assessments.

PMID- 22955599
TI  - Conservation: Tourism ban won't help Indian tigers.

PMID- 22955600
TI  - Bioethics: Tighten up Japan's stem-cell practices.

PMID- 22955602
TI  - Space science: NASA bids are not a popularity contest.

PMID- 22955601
TI  - Toilet technology: Improve sanitation on India's railways.

PMID- 22955603
TI  - Renewable energy: Avoid constructing wind farms on peat.

PMID- 22955604
TI  - Martin Fleischmann (1927-2012).

PMID- 22955605
TI  - Materials science: A hard concept in soft matter.

PMID- 22955606
TI  - Cosmology: The lithium problem.

PMID- 22955607
TI  - Neuroscience: Lessons from heartbreak.

PMID- 22955609
TI  - Surface science: Separation by reconfiguration.

PMID- 22955610
TI  - Astronomy: Outflows from the first quasars.

PMID- 22955611
TI  - Structural biology: A protein engagement RING.

PMID- 22955612
TI  - Presenting ENCODE.

PMID- 22955613
TI  - The making of ENCODE: Lessons for big-data projects.

PMID- 22955614
TI  - Genomics: ENCODE explained.

PMID- 22955617
TI  - The accessible chromatin landscape of the human genome.
AB  - DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have
      underpinned the discovery of all classes of cis-regulatory elements including
      enhancers, promoters, insulators, silencers and locus control regions. Here we
      present the first extensive map of human DHSs identified through genome-wide
      profiling in 125 diverse cell and tissue types. We identify ~2.9 million DHSs
      that encompass virtually all known experimentally validated cis-regulatory
      sequences and expose a vast trove of novel elements, most with highly cell
      selective regulation. Annotating these elements using ENCODE data reveals novel
      relationships between chromatin accessibility, transcription, DNA methylation and
      regulatory factor occupancy patterns. We connect ~580,000 distal DHSs with their
      target promoters, revealing systematic pairing of different classes of distal
      DHSs and specific promoter types. Patterning of chromatin accessibility at many
      regulatory regions is organized with dozens to hundreds of co-activated elements,
      and the transcellular DNase I sensitivity pattern at a given region can predict
      cell-type-specific functional behaviours. The DHS landscape shows signatures of
      recent functional evolutionary constraint. However, the DHS compartment in
      pluripotent and immortalized cells exhibits higher mutation rates than that in
      highly differentiated cells, exposing an unexpected link between chromatin
      accessibility, proliferative potential and patterns of human variation.

PMID- 22955618
TI  - An expansive human regulatory lexicon encoded in transcription factor footprints.
AB  - Regulatory factor binding to genomic DNA protects the underlying sequence from
      cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic
      DNase I footprinting across 41 diverse cell and tissue types, we detected 45
      million transcription factor occupancy events within regulatory regions,
      representing differential binding to 8.4 million distinct short sequence
      elements. Here we show that this small genomic sequence compartment, roughly
      twice the size of the exome, encodes an expansive repertoire of conserved
      recognition sequences for DNA-binding proteins that nearly doubles the size of
      the human cis-regulatory lexicon. We find that genetic variants affecting allelic
      chromatin states are concentrated in footprints, and that these elements are
      preferentially sheltered from DNA methylation. High-resolution DNase I cleavage
      patterns mirror nucleotide-level evolutionary conservation and track the
      crystallographic topography of protein-DNA interfaces, indicating that
      transcription factor structure has been evolutionarily imprinted on the human
      genome sequence. We identify a stereotyped 50-base-pair footprint that precisely
      defines the site of transcript origination within thousands of human promoters.
      Finally, we describe a large collection of novel regulatory factor recognition
      motifs that are highly conserved in both sequence and function, and exhibit cell
      selective occupancy patterns that closely parallel major regulators of
      development, differentiation and pluripotency.

PMID- 22955619
TI  - Architecture of the human regulatory network derived from ENCODE data.
AB  - Transcription factors bind in a combinatorial fashion to specify the on-and-off
      states of genes; the ensemble of these binding events forms a regulatory network,
      constituting the wiring diagram for a cell. To examine the principles of the
      human transcriptional regulatory network, we determined the genomic binding
      information of 119 transcription-related factors in over 450 distinct
      experiments. We found the combinatorial, co-association of transcription factors
      to be highly context specific: distinct combinations of factors bind at specific
      genomic locations. In particular, there are significant differences in the
      binding proximal and distal to genes. We organized all the transcription factor
      binding into a hierarchy and integrated it with other genomic information (for
      example, microRNA regulation), forming a dense meta-network. Factors at different
      levels have different properties; for instance, top-level transcription factors
      more strongly influence expression and middle-level ones co-regulate targets to
      mitigate information-flow bottlenecks. Moreover, these co-regulations give rise
      to many enriched network motifs (for example, noise-buffering feed-forward
      loops). Finally, more connected network components are under stronger selection
      and exhibit a greater degree of allele-specific activity (that is, differential
      binding to the two parental alleles). The regulatory information obtained in this
      study will be crucial for interpreting personal genome sequences and
      understanding basic principles of human biology and disease.

PMID- 22955622
TI  - Observation of interstellar lithium in the low-metallicity Small Magellanic
      Cloud.
AB  - The primordial abundances of light elements produced in the standard theory of
      Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to
      photons, a quantity inferred from observations of the microwave background. The
      predicted primordial (7)Li abundance is four times that measured in the
      atmospheres of Galactic halo stars. This discrepancy could be caused by
      modification of surface lithium abundances during the stars' lifetimes or by
      physics beyond the Standard Model that affects early nucleosynthesis. The lithium
      abundance of low-metallicity gas provides an alternative constraint on the
      primordial abundance and cosmic evolution of lithium that is not susceptible to
      the in situ modifications that may affect stellar atmospheres. Here we report
      observations of interstellar (7)Li in the low-metallicity gas of the Small
      Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The
      present-day (7)Li abundance of the Small Magellanic Cloud is nearly equal to the
      BBN predictions, severely constraining the amount of possible subsequent
      enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements
      can be reconciled with standard BBN with an extremely fine-tuned depletion of
      stellar Li with metallicity. They are also consistent with non-standard BBN.

PMID- 22955621
TI  - The long-range interaction landscape of gene promoters.
AB  - The vast non-coding portion of the human genome is full of functional elements
      and disease-causing regulatory variants. The principles defining the
      relationships between these elements and distal target genes remain unknown.
      Promoters and distal elements can engage in looping interactions that have been
      implicated in gene regulation. Here we have applied chromosome conformation
      capture carbon copy (5C) to interrogate comprehensively interactions between
      transcription start sites (TSSs) and distal elements in 1% of the human genome
      representing the ENCODE pilot project regions. 5C maps were generated for
      GM12878, K562 and HeLa-S3 cells and results were integrated with data from the
      ENCODE consortium. In each cell line we discovered >1,000 long-range interactions
      between promoters and distal sites that include elements resembling enhancers,
      promoters and CTCF-bound sites. We observed significant correlations between gene
      expression, promoter-enhancer interactions and the presence of enhancer RNAs.
      Long-range interactions show marked asymmetry with a bias for interactions with
      elements located ~120 kilobases upstream of the TSS. Long-range interactions are
      often not blocked by sites bound by CTCF and cohesin, indicating that many of
      these sites do not demarcate physically insulated gene domains. Furthermore, only
      ~7% of looping interactions are with the nearest gene, indicating that genomic
      proximity is not a simple predictor for long-range interactions. Finally,
      promoters and distal elements are engaged in multiple long-range interactions to
      form complex networks. Our results start to place genes and regulatory elements
      in three-dimensional context, revealing their functional relationships.

PMID- 22955623
TI  - No meridional plasma flow in the heliosheath transition region.
AB  - Over a two-year period, Voyager 1 observed a gradual slowing-down of radial
      plasma flow in the heliosheath to near-zero velocity after April 2010 at a
      distance of 113.5 astronomical units from the Sun (1 astronomical unit equals 1.5
      * 10(8) kilometres). Voyager 1 was then about 20 astronomical units beyond the
      shock that terminates the free expansion of the solar wind and was immersed in
      the heated non-thermal plasma region called the heliosheath. The expectation from
      contemporary simulations was that the heliosheath plasma would be deflected from
      radial flow to meridional flow (in solar heliospheric coordinates), which at
      Voyager 1 would lie mainly on the (locally spherical) surface called the
      heliopause. This surface is supposed to separate the heliosheath plasma, which is
      of solar origin, from the interstellar plasma, which is of local Galactic origin.
      In 2011, the Voyager project began occasional temporary re-orientations of the
      spacecraft (totalling about 10-25 hours every 2 months) to re-align the Low
      Energy Charged Particle instrument on board Voyager 1 so that it could measure
      meridional flow. Here we report that, contrary to expectations, these
      observations yielded a meridional flow velocity of +3 +/- 11 km s(-1), that is,
      one consistent with zero within statistical uncertainties.

PMID- 22955620
TI  - Landscape of transcription in human cells.
AB  - Eukaryotic cells make many types of primary and processed RNAs that are found
      either in specific subcellular compartments or throughout the cells. A complete
      catalogue of these RNAs is not yet available and their characteristic subcellular
      localizations are also poorly understood. Because RNA represents the direct
      output of the genetic information encoded by genomes and a significant proportion
      of a cell's regulatory capabilities are focused on its synthesis, processing,
      transport, modification and translation, the generation of such a catalogue is
      crucial for understanding genome function. Here we report evidence that three
      quarters of the human genome is capable of being transcribed, as well as
      observations about the range and levels of expression, localization, processing
      fates, regulatory regions and modifications of almost all currently annotated and
      thousands of previously unannotated RNAs. These observations, taken together,
      prompt a redefinition of the concept of a gene.

PMID- 22955616
TI  - An integrated encyclopedia of DNA elements in the human genome.
AB  - The human genome encodes the blueprint of life, but the function of the vast
      majority of its nearly three billion bases is unknown. The Encyclopedia of DNA
      Elements (ENCODE) project has systematically mapped regions of transcription,
      transcription factor association, chromatin structure and histone modification.
      These data enabled us to assign biochemical functions for 80% of the genome, in
      particular outside of the well-studied protein-coding regions. Many discovered
      candidate regulatory elements are physically associated with one another and with
      expressed genes, providing new insights into the mechanisms of gene regulation.
      The newly identified elements also show a statistical correspondence to sequence
      variants linked to human disease, and can thereby guide interpretation of this
      variation. Overall, the project provides new insights into the organization and
      regulation of our genes and genome, and is an expansive resource of functional
      annotations for biomedical research.

PMID- 22955624
TI  - Flexible metal-oxide devices made by room-temperature photochemical activation of
      sol-gel films.
AB  - Amorphous metal-oxide semiconductors have emerged as potential replacements for
      organic and silicon materials in thin-film electronics. The high carrier mobility
      in the amorphous state, and excellent large-area uniformity, have extended their
      applications to active-matrix electronics, including displays, sensor arrays and
      X-ray detectors. Moreover, their solution processability and optical transparency
      have opened new horizons for low-cost printable and transparent electronics on
      plastic substrates. But metal-oxide formation by the sol-gel route requires an
      annealing step at relatively high temperature, which has prevented the
      incorporation of these materials with the polymer substrates used in high
      performance flexible electronics. Here we report a general method for forming
      high-performance and operationally stable metal-oxide semiconductors at room
      temperature, by deep-ultraviolet photochemical activation of sol-gel films. Deep
      ultraviolet irradiation induces efficient condensation and densification of oxide
      semiconducting films by photochemical activation at low temperature. This
      photochemical activation is applicable to numerous metal-oxide semiconductors,
      and the performance (in terms of transistor mobility and operational stability)
      of thin-film transistors fabricated by this route compares favourably with that
      of thin-film transistors based on thermally annealed materials. The field-effect
      mobilities of the photo-activated metal-oxide semiconductors are as high as 14
      and 7 cm(2) V(-1) s(-1) (with an Al(2)O(3) gate insulator) on glass and polymer
      substrates, respectively; and seven-stage ring oscillators fabricated on polymer
      substrates operate with an oscillation frequency of more than 340 kHz,
      corresponding to a propagation delay of less than 210 nanoseconds per stage.

PMID- 22955627
TI  - DETERMINATION OF CRITICAL POWER AND ANAEROBIC   WORK CAPACITY: IS ONE TEST BETTER
      THAN TWO?

PMID- 22955625
TI  - Highly stretchable and tough hydrogels.
AB  - Hydrogels are used as scaffolds for tissue engineering, vehicles for drug
      delivery, actuators for optics and fluidics, and model extracellular matrices for
      biological studies. The scope of hydrogel applications, however, is often
      severely limited by their mechanical behaviour. Most hydrogels do not exhibit
      high stretchability; for example, an alginate hydrogel ruptures when stretched to
      about 1.2 times its original length. Some synthetic elastic hydrogels have
      achieved stretches in the range 10-20, but these values are markedly reduced in
      samples containing notches. Most hydrogels are brittle, with fracture energies of
      about 10 J m(-2) (ref. 8), as compared with ~1,000 J m(-2) for cartilage and
      ~10,000 J m(-2) for natural rubbers. Intense efforts are devoted to synthesizing
      hydrogels with improved mechanical properties; certain synthetic gels have
      reached fracture energies of 100-1,000 J m(-2) (refs 11, 14, 17). Here we report
      the synthesis of hydrogels from polymers forming ionically and covalently
      crosslinked networks. Although such gels contain ~90% water, they can be
      stretched beyond 20 times their initial length, and have fracture energies of
      ~9,000 J m(-2). Even for samples containing notches, a stretch of 17 is
      demonstrated. We attribute the gels' toughness to the synergy of two mechanisms:
      crack bridging by the network of covalent crosslinks, and hysteresis by unzipping
      the network of ionic crosslinks. Furthermore, the network of covalent crosslinks
      preserves the memory of the initial state, so that much of the large deformation
      is removed on unloading. The unzipped ionic crosslinks cause internal damage,
      which heals by re-zipping. These gels may serve as model systems to explore
      mechanisms of deformation and energy dissipation, and expand the scope of
      hydrogel applications.

PMID- 22955628
TI  - Effect of moderate-intensity exercise training on the cognitive function of young
      adults with intellectual disabilities.
AB  - In addition to cognitive impairment, young adults with intellectual disabilities
      (IDs) are also more likely to be in poor health. Exercise may help ameliorate
      both of these deficits. While the health benefits of exercise are well documented
      and understood, the cognitive benefits of exercise are emerging. Exercise has
      been shown to improve the cognitive function of young, old, and diseased
      populations but few studies have evaluated the effect of exercise training on the
      cognitive functioning of individuals with IDs. The purpose of this study was to
      determine the effect of moderate-intensity exercise training on the cognitive
      function of young adults with IDs. Fourteen students (age, 19.4 +/- 1.3 years)
      with mild to moderate IDs participated in an 8-week comprehensive exercise
      intervention program based on circuit training, aerobic dancing, and adapted
      sport activities. Sessions lasted 45 minutes, and intensity was maintained at 60
      70% of maximum heart rate (HR(max)). Aerobic fitness was assessed via the Young
      Men's Christian Association (YMCA) step test, and intellectual functioning was
      assessed via 3 subtests from the Woodcock-Johnson III Tests of Cognitive
      Abilities once before and after the intervention. Performance was significantly
      improved on all 3 cognitive tests (all, p < 0.002). Aerobic fitness also
      significantly improved (p < 0.002). The mean percent increase in processing
      speed, a measure taking into account each individual's performance on the 3
      subtests, was 103%. The mean individual improvement in aerobic fitness was 17.5%.
      Moderate-intensity exercise training can yield robust improvements in the
      cognitive functioning and aerobic fitness of young adults with IDs. These effects
      support the inclusion of exercise into the lives of young adults with ID to
      promote their physical and cognitive health. Fourteen students (age, 19.4 +/- 1.3
      years) with mild to moderate IDs participated in an 8-week comprehensive exercise
      intervention program based on circuit training, aerobic dancing, and adapted
      sport activities. Sessions lasted 45 minutes and intensity Powered by Editorial
      Manager and Preprint Manager from Aries Systems Corporation was maintained at 60
      70% of HR(max). Aerobic fitness was assessed via the YMCA step test, and
      intellectual functioning was assessed via 3 subtests from the Woodcock-Johnson
      III Tests of Cognitive Abilities once before and after the intervention.
      Performance was significantly improved on all 3 cognitive tests (all, p < 0.002).
      Aerobic fitness also significantly improved (p < 0.002). The mean percent
      increase in processing speed, a measure taking into account each individual's
      performance on the 3 subtests, was 103%. The mean individual improvement in
      aerobic fitness was 17.5%. Moderate-intensity exercise training can yield robust
      improvements in the cognitive functioning and aerobic fitness of young adults
      with IDs. These effects support the inclusion of exercise into the lives of young
      adults with ID to promote their physical and cognitive health.

PMID- 22955629
TI  - Is there a difference between active and less active children and adolescents in
      jump performance?
AB  - Training and activity level are important predictors of motor development. At
      present, many children and adolescents do not participate in any sport activity
      in their leisure time. In this investigation, we analyzed the level of
      performance of the stretch and shortening cycle (SSC) in childhood and youth.
      Data of 801 participants were recorded for 2 separate groups, those in elite
      soccer associations and those who were less active in their leisure time. All the
      participants completed the following performance tests: the squat jump, the
      countermovement jump and the drop jump from varying heights. All the participants
      answered a questionnaire to determine their level of activity. Comparisons of
      performance were made across the 2 groups. The data showed a significant (p <
      0.05) advantage for soccer players in nearly every variable involved in the
      performance of the SSC. The analysis of the questionnaire highlights the fact
      that approximately a quarter of students are inactive in their leisure time,
      which means they do not participate in any sport activity except for school
      sports. The data show that many children and adolescents do not participate in
      sport activities in their leisure time. Furthermore, many of these children and
      adolescents have a body mass index >25. The results of this investigation support
      the fact that inactivity is correlated with a low training level in children and
      youth.

PMID- 22955630
TI  - Electrophoretic separation of myosin heavy chain isoforms using a modified mini
      gel system.
AB  - The electrophoretic separation of myosin heavy chain isoforms from muscle biopsy
      homogenates has been widely practiced in the field of exercise physiology to
      examine how intrinsic (i.e., aging) and extrinsic (i.e., training) factors affect
      muscle phenotype. In the past, various research groups have used large and mini
      polyacrylamide gel systems to perform this delicate methodology. As technology
      has progressed, additional gel formats have been introduced, but available
      methodologies appear to be lacking. In this investigation, we successfully
      separated 3 distinct myosin heavy chain isoforms from various muscle samples
      using a modified mini gel system that can load up to 26 samples per gel. This
      article will outline our allocated protocol and discuss potential troubleshooting
      considerations for other researchers performing this intricate methodology. The
      outlined methodology has resulted in an ability to clearly resolute 3 distinct
      bands at molecular weights attributed to the myosin heavy chain isoforms in human
      skeletal muscle at a wide range of human ages (20-78 years). As additional
      technologies become available, the need to modify and adapt existing
      electrophoretic protocols for myosin heavy chain isoform separation and other
      protocols will continue to be evident.

PMID- 22955631
TI  - Correlates of egg size variation in a population of house sparrow Passer
      domesticus.
AB  - Propagule size represents an important life-history trait under maternal control.
      Despite a positive relationship between propagule size and components of fitness,
      propagule size displays tremendous amounts of variation which causes are poorly
      understood within natural populations. With a study of a house sparrows Passer
      domesticus, we investigate maternal and environmental correlates of egg size,
      quantify variation in egg size within and between females and broods, and
      estimate heritability. Egg size had a curvilinear relationship with clutch size
      and decreased significantly in subsequent broods within seasons. Furthermore, egg
      size increased with maternal body mass, was positively affected by spring
      temperatures and curvilinearly related to temperature during the 2 weeks prior to
      egg laying. Some 46.4 % of variation in egg size was due to differences between
      females, and 21.9 % was explained by variation between broods by the same female.
      The heritability of egg size was low (h (2) = 0.26) compared to estimates from
      other studies (h (2) > 0.6). The present study challenges the recent idea that
      egg size is an inflexible maternal characteristic with very high additive genetic
      variance, and suggests that females are subject to both intrinsic and extrinsic
      constraints prior to and during egg formation, leading to the observed plasticity
      in egg size. In a general sense, propagule size could be expected to be both
      limited by and adaptively adjusted in accordance to prevailing environmental
      conditions.

PMID- 22955632
TI  - A case of multiple system atrophy with normal dopamine transporter imaging.

PMID- 22955633
TI  - Clinically biphasic myasthenia gravis with both AChR and MuSK antibodies.

PMID- 22955635
TI  - Advanced esophageal cancer with an esophago-bronchial fistula successfully
      treated by chemoradiotherapy following esophageal bypass surgery: report of a
      case.
AB  - Esophageal bypass surgery using a gastric tube prior to definitive
      chemoradiotherapy in preparation for the formation of esophago-tracheal or
      bronchial fistula is a possible strategy for esophageal cancer invading the
      airway. This report presents the case of a patient with esophageal cancer
      involving the left main bronchus who underwent esophageal bypass followed by
      definitive chemoradiotherapy and who has achieved long-term survival without
      deterioration of his quality of life, in spite of the development of a malignant
      esophago-bronchial fistula.

PMID- 22955634
TI  - Generalized tonic-clonic seizures and antiepileptic drugs during pregnancy--a
      matter of importance for the baby?
AB  - This study investigates the impact of generalized tonic-clonic seizures (GTCS)
      and antiepileptic drugs (AED) during pregnancy on gestational age (GA) and
      anthropometric data of newborns. One hundred twenty-nine singleton pregnancies
      resulting in live births from September 1999 to October 2010 in 106 women with
      epilepsy on AED therapy, recorded within the framework of the EURAP
      (International Registry of Antiepileptic Drugs and Pregnancy) program at the
      Department of Neurology, Medical University Innsbruck, Austria, were studied.
      Occurrence of >= 1 GTCS during pregnancy was associated with a shorter GA [median
      (range) 37.5 [35.1-41.6] vs. 39.7 [29.1-46.3] weeks; p <= 0.001], an overall five
      times higher preterm risk (p = 0.042) and a reduced birth weight in boys (2,900
      [2,050-3,870] vs. 3,205 [1,575-4,355] g; p = 0.040). In primipara, when compared
      to multipara, GTCS >= 1 significantly reduced the GA (37.9 [35.1-41.6] vs. 39.7
      [29.4-44.9] weeks; p = 0.020) and raised the incidence of low birth weight (LBW)
      (p = 0.022) in neonates. Antiepileptic drug polytherapy significantly increased
      the risk for small-for-gestational-age regarding weight (SGA(W); p = 0.035) and
      regarding weight and/or length (SGA(W/L); p = 0.046) when compared to
      monotherapy. GTCS during pregnancy was associated with diverse negative effects
      comprising shorter GA, an increased incidence of prematurity and LBW in
      primiparous women. Furthermore, AED polytherapy was correlated with an enhanced
      risk for SGA delivery. Re-evaluating the need for drug therapy (in particular
      polytherapy), maintaining seizure control for a given period before pregnancy and
      counseling about the importance of preventing GTCS might improve pregnancy
      outcome in women with epilepsy.

PMID- 22955637
TI  - Unzipping the role of chirality in nanoscale self-assembly of tripeptide
      hydrogels.
AB  - Change of chirality is a useful tool to manipulate the aqueous self-assembly
      behaviour of uncapped, hydrophobic tripeptides. In contrast with other short
      peptides, these tripeptides form hydrogels at a physiological pH without the aid
      of organic solvents or end-capping groups (e.g. Fmoc). The novel hydrogel forming
      peptide (D)Leu-Phe-Phe ((D)LFF) and its epimer Leu-Phe-Phe (LFF) exemplify
      dramatic supramolecular effects induced by subtle changes to stereochemistry.
      Only the d-amino acid-containing peptide instantly forms a hydrogel in aqueous
      solution following a pH switch, generating long fibres (>100 MUm) that entangle
      into a 3D network. However, unexpected nanostructures are observed for both
      peptides and they are particularly heterogeneous for LFF. Structural analyses
      using CD, FT-IR and fluorescent amyloid staining reveal anti-parallel beta-sheets
      for both peptides. XRD analysis also identifies key distances consistent with
      beta-sheet formation in both peptides, but suggests additional high molecular
      order and extended molecular length for (D)LFF only. Molecular modelling of the
      two peptides highlights the key interactions responsible for self-assembly; in
      particular, rapid self-assembly of (D)LFF is promoted by a phenylalanine zipper,
      which is not possible because of steric factors for LFF. In conclusion, this
      study elucidates for the first time the molecular basis for how chirality can
      dramatically influence supramolecular organisation in very short peptide
      sequences.

PMID- 22955636
TI  - Retinal vasculitis in rheumatic diseases: an unseen burden.
AB  - Retinal vascular inflammation, a potentially blinding condition (herein: retinal
      vasculitis (RV)) is commonly associated with a heterogeneous group of diseases
      characterized by systemic inflammatory cell infiltration and/or necrosis of blood
      vessel walls. RV may arise as an isolated ocular disorder, as part of systemic
      vasculitis (Wegener's granulomatosis and Adamantiadis-Behcet Disease), or it can
      be secondary to an underlying connective tissue disease (systemic lupus
      erythematosus, sarcoidosis, and rheumatoid arthritis), systemic infection, or
      malignancy. Depending on the type of RV, it can be a potentially disabling
      condition, in the short or long term. Early diagnosis is the key to successful
      treatment and better prognosis. However, early diagnosis can be difficult,
      because these conditions usually present with nonspecific visual symptoms for a
      long period before diagnostic manifestations occur. The retina should be examined
      in warranted patients with verified rheumatic disease, since retinal vasculitis
      may be asymptomatic at the beginning (peripheral retinal disease). RV can be
      detected clinically (often accompanied by uveitis, scleritis, or macular edema)
      or revealed on fluorescein fundus angiography, even if minimal signs of retinal
      vessel inflammation are present. RV may also represent one of the possible extra
      articular manifestations of the rheumatic disease. Rheumatologists should be
      familiar with the ocular manifestations of these disorders, since they may not
      only be sight-threatening, but more importantly, could be the presenting or even
      the very first manifestations of active, potentially lethal systemic disease in a
      patient with nonspecific rheumatologic presentation.

PMID- 22955638
TI  - An investigation into factors affecting electron density calibration for a
      megavoltage cone-beam CT system.
AB  - There is a growing interest in the use of megavoltage cone-beam computed
      tomography (MV CBCT) data for radiotherapy treatment planning. To calculate
      accurate dose distributions, knowledge of the electron density (ED) of the
      tissues being irradiated is required. In the case of MV CBCT, it is necessary to
      determine a calibration-relating CT number to ED, utilizing the photon beam
      produced for MV CBCT. A number of different parameters can affect this
      calibration. This study was undertaken on the Siemens MV CBCT system, MVision, to
      evaluate the effect of the following parameters on the reconstructed CT pixel
      value to ED calibration: the number of monitor units (MUs) used (5, 8, 15 and 60
      MUs), the image reconstruction filter (head and neck, and pelvis), reconstruction
      matrix size (256 by 256 and 512 by 512), and the addition of extra solid water
      surrounding the ED phantom. A Gammex electron density CT phantom containing EDs
      from 0.292 to 1.707 was imaged under each of these conditions. The linear
      relationship between MV CBCT pixel value and ED was demonstrated for all MU
      settings and over the range of EDs. Changes in MU number did not dramatically
      alter the MV CBCT ED calibration. The use of different reconstruction filters was
      found to affect the MV CBCT ED calibration, as was the addition of solid water
      surrounding the phantom. Dose distributions from treatment plans calculated with
      simulated image data from a 15 MU head and neck reconstruction filter MV CBCT
      image and a MV CBCT ED calibration curve from the image data parameters and a 15
      MU pelvis reconstruction filter showed small and clinically insignificant
      differences. Thus, the use of a single MV CBCT ED calibration curve is unlikely
      to result in any clinical differences. However, to ensure minimal uncertainties
      in dose reporting, MV CBCT ED calibration measurements could be carried out using
      parameter-specific calibration measurements.

PMID- 22955639
TI  - Application of AAPM TG 119 to volumetric arc therapy (VMAT).
AB  - The purpose of this study was to create AAPM TG 119 benchmark plans for
      volumetric arc therapy (VMAT) and to compare VMAT plans with IMRT plan data. AAPM
      TG 119 proposes a set of test clinical cases for testing the accuracy of IMRT
      planning and delivery system. For these test cases, we generated two treatment
      plans, the first plan using 7-9 static dMLC IMRT fields and a second plan
      utilizing one- or two-arc VMAT technique. Dose optimization and calculations
      performed using 6 MV photons and Eclipse treatment planning system. Dose
      prescription and planning objectives were set according to the TG 119 goals.
      Plans were scored based on TG 119 planning objectives. Treatment plans were
      compared using conformity index (CI) for reference dose and homogeneity index
      (HI) (for D(5)-D(95)). For test cases prostate, head-and-neck, C-shape and
      multitarget prescription dose are 75.6 Gy, 50.4 Gy, 50 Gy and 50 Gy,
      respectively. VMAT dose distributions were comparable to dMLC IMRT plans. Our
      planning results matched TG 119 planning results. For treatment plans studied,
      conformity indices ranged from 1.05-1.23 (IMRT) and 1.04-1.23 (VMAT). Homogeneity
      indices ranged from 4.6%-11.0% (IMRT) and 4.6%-10.5% (VMAT). The ratio of total
      monitor units necessary for dMLC IMRT to that of VMAT was in the range of 1.1
      2.0. AAPM TG 119 test cases are useful to generate VMAT benchmark plans. At
      preclinical implementation stage, plan comparison of VMAT and IMRT plans of AAPM
      TG 119 test case allowed us to understand basic capabilities of VMAT technique.

PMID- 22955640
TI  - Mathematical modeling of the optimum pulse structure for safe and effective photo
      epilation using broadband pulsed light.
AB  - The objective of this work is the investigation of intense pulsed light (IPL)
      photoepilation using Monte Carlo simulation to model the effect of the output
      dosimetry with millisecond exposure used by typical commercial IPL systems. The
      temporal pulse shape is an important parameter, which may affect the biological
      tissue response in terms of efficacy and adverse reactions. This study
      investigates the effect that IPL pulse structures, namely free discharge, square
      pulse, close, and spaced pulse stacking, has on hair removal. The relationship
      between radiant exposure distribution during the IPL pulse and chromophore
      heating is explored and modeled for hair follicles and the epidermis using a
      custom Monte Carlo computer simulation. Consistent square pulse and close pulse
      stacking delivery of radiant exposure across the IPL pulse is shown to generate
      the most efficient specific heating of the target chromophore, whilst sparing the
      epidermis, compared to free discharge and pulse stacking pulse delivery. Free
      discharge systems produced the highest epidermal temperature in the model. This
      study presents modeled thermal data of a hair follicle in situ, indicating that
      square pulse IPL technology may be the most efficient and the safest method for
      photoepilation. The investigation also suggests that the square pulse system
      design is the most efficient, as energy is not wasted during pulse exposure or
      lost through interpulse delay times of stacked pulses.

PMID- 22955641
TI  - Comparing dose in the build-up region between compensator- and MLC-based IMRT.
AB  - The build-up dose in the megavoltage photon beams can be a limiting factor in
      intensity-modulated radiation therapy (IMRT) treatments. Excessive surface dose
      can cause patient discomfort and treatment interruptions, while underdosing may
      lead to tumor repopulation and local failure. Dose in the build-up region was
      investigated for IMRT delivery with solid brass compensator technique(compensator
      based IMRT) and compared with that of multileaf collimator (MLC)-based IMRT. A
      Varian Trilogy linear accelerator equipped with an MLC was used for beam
      delivery. A special solid brass step-wise compensator was designed and built for
      testing purposes. Two step-and-shoot MLC fields were programmed to produce a
      similar modulated step-wise dose profile. The MLC and compensator dose profiles
      were measured and adjusted to match at the isocenter depth of 10 cm. Build-up
      dose in the 1-5 mm depth range was measured with an ultrathin window, fixed
      volume parallel plate ionization chamber. Monte Carlo simulations were used to
      model the brass compensator and step-and-shoot MLC fields. The measured and
      simulated profiles for the two IMRT techniques were matched at the isocenter
      depth of 10 cm. Different component contributions to the shallow dose, including
      the MLC scatter, were quantified. Mean spectral energies for the open and
      filtered beams were calculated. The compensator and MLC profiles at 10 cm depth
      were matched better than +/- 1.5%. The build-up dose was up to 7% lower for
      compensator IMRT compared to MLC IMRT due to beam hardening in the brass. Low
      energy electrons contribute 22% and 15% dose at 1 mm depth for compensator and
      MLC modalities, respectively. Compensator-based IMRT delivers less dose in the
      build-up region than MLC-based IMRT does, even though a compensator is closer to
      the skin than the MLC.

PMID- 22955642
TI  - Ion recombination corrections of ionization chambers in flattening filter-free
      photon radiation.
AB  - The flattening filter free (FFF) X-rays can provide much higher dose rate at the
      treatment target compared to the conventional flattened X-rays. However, the
      substantial increase of dose rate for FFF beams may affect the ion recombination
      correction factor, which is required for accurate measurements using ionization
      chambers in clinical dosimetry. The purpose of this work is to investigate the
      ion recombination of three types of commonly used ion chambers (Farmer, PinPoint
      and plane-parallel) in the FFF photon radiation. Both 6 MV and 10 MV flattened
      and FFF beams were fully commissioned on a Varian TrueBeam linear accelerator.
      The ion recombination correction factor, P(ion), was determined using the two
      voltage technique for a 0.6 cc Farmer chamber, a 0.015 cc PinPoint chamber, and a
      0.02 cc parallel-plate chamber at different source-to-axis distances (SAD) in a
      solid water phantom or water tank phantom at a depth of 10 cm in a 10 * 10 cm(2)
      field. Good repeatability of measurements was demonstrated. Less than 1%
      difference in P(ion) between the flattened and FFF photons for all three ion
      chambers was observed. At a SAD of 100 cm and a depth of 10 cm for a 10 * 10
      cm(2) field, P(ion) for the Farmer chamber was 1.004 and 1.008 for the 6 MV
      flattened and FFF beams, respectively. At the same setup using the Farmer
      chamber, P(ion) was 1.002 and 1.015 for the 10MV flattened and FFF beams,
      respectively. All P(ion) results for the Farmer, PinPoint, or parallel plate
      chamber in the 6 MV and 10 MV flattened and FFF beams were within 2% from the
      unity (1 <= P(ion) < 1.02). The P(ion) ratio of the FFF to flattened beams was
      0.99~1.01 for both 6 MV and 10 MV photons. The ion recombination effect of the
      Farmer, PinPoint, and plane-parallel chamber in the FFF beams is not
      substantially different from that in the conventional flattened beams.

PMID- 22955643
TI  - Impact of different CBCT imaging monitor units, reconstruction slice thicknesses,
      and planning CT slice thicknesses on the positioning accuracy of a MV-CBCT system
      in head-and-neck patients.
AB  - The purpose of this study was to investigate the impact of different CBCT imaging
      monitor units (MUs), reconstruction slice thicknesses, and planning CT slice
      thicknesses on the positioning accuracy of a megavoltage cone-beam computed
      tomography (MV-CBCT) system in image-guided radiation therapy (IGRT) in head-and
      neck patients. The MV-CBCT system was a Siemens MVision, a commercial system
      integrated into the Siemens ONCOR linear accelerator. The positioning accuracy of
      the MV-CBCT system was determined using an anthropomorphic phantom while varying
      the MV-CBCT imaging MU, reconstruction slice thickness, and planning CT slice
      thickness. A total of 240 CBCT images from six head-and-neck patients who
      underwent intensity-modulated radiotherapy (IMRT) treatment were acquired and
      reconstructed using different MV-CBCT scanning protocols. The interfractional
      setup errors of the patients were retrospectively analyzed for different imaging
      MUs, reconstruction slice thicknesses, and planning CT slice thicknesses. Using
      the anthropomorphic phantom, the largest measured mean deviation component and
      standard deviation of the MVision in 3D directions were 1.3 and 1.0 mm,
      respectively, for different CBCT imaging MUs, reconstruction slice thicknesses,
      and planning CT slice thicknesses. The largest setup group system error (M),
      system error (Sigma), and random error (sigma) from six head-and-neck patients
      were 0.6, 1.2, and 1.7 mm, respectively. No significant difference was found in
      the positioning accuracy of the MV-CBCT system between the 5 and 8 MUs, and
      between the 1 and 3 mm reconstruction slice thicknesses. A thin planning CT slice
      thickness may achieve higher positioning precision using the phantom measurement,
      but no significant difference was found in clinical setup precision between the 1
      and 3 mm planning CT slice thicknesses.

PMID- 22955644
TI  - Providing a fast conversion of total dose to biological effective dose (BED) for
      hybrid seed brachytherapy.
AB  - Optimization of permanent seed implant brachytherapy plans for treatment of
      prostate cancer should be based on biological effective dose (BED) distributions,
      since dose does not accurately represent biological effects between different
      types of sources. Currently, biological optimization for these plans is not
      feasible due to the amount of time necessary to calculate the BED distribution.
      This study provides a fast calculation method, based on the total dose, to
      calculate the BED distribution. Distributions of various numbers of hybrid seeds
      were used to calculate total dose distributions, as well as BED distributions.
      Hybrid seeds are a mixture of different isotopes (in this study (125)I and
      (103)Pd). Three ratios of hybrid seeds were investigated: 25/75, 50/50, and
      75/25. The total dose and BED value from each voxel were coupled together to
      produce graphs of total dose vs. BED. Equations were then derived from these
      graphs. The study investigated four types of tissue: bladder, rectum, prostate,
      and other normal tissue. Equations were derived from the total dose - BED
      correspondence. Accuracy of conversion from total dose to BED was within 2 Gy;
      however, accuracy of conversion was found to be better for high total dose
      regions as compared to lower dose regions. The method introduced in this paper
      allows one to perform fast conversion of total dose to BED for brachytherapy
      using hybrid seeds, which makes the BED-based plan optimization practical. The
      method defined here can be extended to other ratios, as well as other tissues
      that are affected by permanent seed implant brachytherapy (i.e., breast).

PMID- 22955645
TI  - The feasibility study of using multiple partial volumetric-modulated arcs therapy
      in early stage left-sided breast cancer patients.
AB  - The purpose of this study was to assess the feasibility of using a multiple
      partial volumetric-modulated arcs therapy (MP-VMAT) technique on the left breast
      irradiation and to evaluate the dosimetry and treatment efficiency. Ten patients
      with left-sided breast cancer who had been treated by whole breast irradiation
      were selected for the treatment plan evaluation by using six partial volumetric
      modulated arcs. Each arc consisted of a 50 degrees  gantry rotation. The planning
      target volumes and the normal organs, including the right breast, the bilateral
      lungs, left ventricle, heart, and unspecified tissue, were contoured on the CT
      images. Dose-volume histograms were generated and the delivery time for each arc
      was recorded. The PTV received greater than 95% of the V(95) for all cases, and
      the maximum dose was within +/- 1% of 110% of the prescription dose. The mean
      homogeneity index (HI) was 10.61 +/- 0.99, and mean conformity index (CI) was
      1.21 +/- 0.03. The mean dose, V(5), V(10), V(25), and V(30) of the heart were
      7.61 +/- 1.38 Gy, 59.73% +/- 15.87%, 24.39%+/- 6.82%, 2.52%+/- 1.11%, and 1.57%
      +/- 0.71%, respectively. The volume of the left ventricle receiving 25 Gy was
      5.15% +/- 2.23%. The total lung mean dose was 5.57 +/- 0.36 Gy, with V(5) of
      25.39% +/- 3.88% and V(20) of 5.66% +/- 0.89%. The right breast received a mean
      dose of 2.13 +/- 0.22 Gy, with V(5) of 1.83% +/- 1.22% and V(10) of 0.04% +/-
      0.12%. The mean dose of unspecified tissue was 5.34 +/- 0.37 Gy and V(5) was
      22.23% +/- 1.57%. The volume of the unspecified tissue receiving 50 Gy was 0.50%
      +/- 0.14%. The mean delivery time for each arc was 13.9 seconds. The average MU
      among ten patients was 511 MU (range 443 to 594 MUs). The MP-VMAT technique for
      the left-sided breast cancer patients achieved adequate target dose coverage
      while maintaining low doses to organs-at-risk, and therefore reduced the
      potential for induction of second malignancy and side effects. The highly
      efficient treatment delivery would be beneficial for improving patient
      throughput, providing patient comfort, and achieving precise treatment with the
      breathing control system.

PMID- 22955646
TI  - Dose distribution changes with shielding disc misalignments and wrong
      orientations in breast IOERT: a Monte Carlo - GEANT4 and experimental study.
AB  - One of the most relevant risks in breast intraoperative electron radiotherapy
      (IOERT) is the incorrect positioning of the shielding disc. If such a setup error
      occurs, the treatment zone could receive a nonuniform dose delivery, and a
      considerable part of the electron beam could hit - and irradiate - the patient's
      healthy tissue. However misalignment and tilt angle of the shielding disc can be
      evaluated, but it is not possible to measure the corresponding in vivo dose
      distribution. This led us to develop a simulation using the Geant4 Monte Carlo
      toolkit to study the effects of disc configuration on dose distribution. Some
      parameters were investigated: the shielding factor (SF), the radiation back
      scattering factor (BSF), the volume-dose histogram in the treatment zone, and the
      maximum leakage dose (MLD) in normal tissue. A lateral shift of the disc (in the
      plane perpendicular to the beam axis) causes a decrease in SF (from 4% for a
      misalignment of 5 mm to 40% for a misalignment of 40 mm), but no relevant dose
      variations were found for a tilt angle until 10 degrees . In the same uncorrected
      disc positions, the BSF shows no significant change. MLD rises to 3.45 Gy for a
      14 mm misalignment and 4.60 Gy for 30 degrees  tilt angle when the prescribed
      dose is 21 Gy. The simulation results are compared with the experimental ones,
      and allow an a posteriori estimation of the dose distribution in the breast
      target and underlying healthy tissue. This information could help the surgical
      team choose a more correct clinical setup, and assist in quantifying the degree
      of success or failure of an IOERT breast treatment.

PMID- 22955647
TI  - A measure to evaluate deformable registration fields in clinical settings.
AB  - Deformable registration has migrated from a research topic to a widely used
      clinical tool that can improve radiotherapeutic treatment accuracy by tracking
      anatomical changes. Although various mathematical formulations have been reported
      in the literature and implemented in commercial software, we lack a
      straightforward method to verify a given solution in routine clinical use. We
      propose a metric using concepts derived from vector analysis that complements the
      standard evaluation tools to identify unrealistic wrappings in a displacement
      field. At the heart of the proposed procedure is identification of vortexes in
      the displacement field that do not correspond to underlying anatomical changes.
      Vortexes are detected and their intensity quantified using the CURL operator and
      presented as a vortex map overlaid on the original anatomy for rapid
      identification of problematic regions. We show application of the proposed metric
      on clinical scenarios of adaptive radiotherapy and treatment response assessment,
      where the CURL operator quantitatively detected errors in the displacement field
      and identified problematic regions that were invisible to classical voxel-based
      evaluation methods. Unrealistic warping not visible to standard voxel-based
      solution assessment can produce erroneous results when the deformable solution is
      applied on a secondary dataset, such as dose matrix in adaptive therapy or PET
      data for treatment response assessment. The proposed metric for evaluating
      deformable registration provides increased usability and accuracy of detecting
      unrealistic deformable registration solutions when compared to standard intensity
      based approaches. It is computationally efficient and provides a valuable
      platform for the clinical acceptance of image-guided radiotherapy.

PMID- 22955648
TI  - Effects of titanium mesh implant on dosimetry during Gamma Knife radiosurgery.
AB  - Calvarial reconstruction following resection of tumors involving the skull is
      often followed by stereotactic radiosurgery. Prior studies have addressed the
      effects of various cranioplasty materials on dose distributions in linac-based
      radiosurgery. We aim to determine the effects of titanium mesh implants on Gamma
      Knife dose. Radiation backscatter and transmission were measured for eight types
      of titanium mesh using film, ion chamber, and Theratron Co-60 teletherapy device.
      A single mesh was selected for Gamma Knife irradiation using a CaSO(4) skull
      filled with ballistics gel. Dose profiles for reconstructed and intact skulls
      were compared with the planning system prediction at 2.5 and 5.5 cm depth.
      Titanium contact backscatter and transmission dose perturbations ranged from -18%
      to 23%. Radiation dose measured at 1.5 cm below the calvarial implant increased
      by 0.5% to 3.3% relative to bone. Measured Gamma Knife dose profile diameters
      agreed with expected profiles. Maximum dose within the intact phantom was 3% less
      than planned due to skull attenuation. Maximum dose within the reconstructed
      phantom was between the intact phantom and planned doses. Titanium mesh implants
      and hydroxyapatite cranioplasty result in minimal alteration (< 3%) in the
      delivered Gamma Knife dose.

PMID- 22955649
TI  - Evaluation of the efficiency and effectiveness of independent dose calculation
      followed by machine log file analysis against conventional measurement based IMRT
      QA.
AB  - Experimental methods are commonly used for patient-specific IMRT delivery
      verification. There are a variety of IMRT QA techniques which have been proposed
      and clinically used with a common understanding that not one single method can
      detect all possible errors. The aim of this work was to compare the efficiency
      and effectiveness of independent dose calculation followed by machine log file
      analysis to conventional measurement-based methods in detecting errors in IMRT
      delivery. Sixteen IMRT treatment plans (5 head-and-neck, 3 rectum, 3 breast, and
      5 prostate plans) created with a commercial treatment planning system (TPS) were
      recalculated on a QA phantom. All treatment plans underwent ion chamber (IC) and
      2D diode array measurements. The same set of plans was also recomputed with
      another commercial treatment planning system and the two sets of calculations
      were compared. The deviations between dosimetric measurements and independent
      dose calculation were evaluated. The comparisons included evaluations of DVHs and
      point doses calculated by the two TPS systems. Machine log files were captured
      during pretreatment composite point dose measurements and analyzed to verify data
      transfer and performance of the delivery machine. Average deviation between IC
      measurements and point dose calculations with the two TPSs for head-and-neck
      plans were 1.2 +/- 1.3% and 1.4 +/- 1.6%, respectively. For 2D diode array
      measurements, the mean gamma value with 3% dose difference and 3 mm distance-to
      agreement was within 1.5% for 13 of 16 plans. The mean 3D dose differences
      calculated from two TPSs were within 3% for head-and-neck cases and within 2% for
      other plans. The machine log file analysis showed that the gantry angle, jaw
      position, collimator angle, and MUs were consistent as planned, and maximal MLC
      position error was less than 0.5 mm. The independent dose calculation followed by
      the machine log analysis takes an average 47 +/- 6 minutes, while the
      experimental approach (using IC and 2D diode array measurements) takes an average
      about 2 hours in our clinic. Independent dose calculation followed by machine log
      file analysis can be a reliable tool to verify IMRT treatments. Additionally,
      independent dose calculations have the potential to identify several problems
      (heterogeneity calculations, data corruptions, system failures) with the primary
      TPS, which generally are not identifiable with a measurement-based approach.
      Additionally, machine log file analysis can identify many problems (gantry,
      collimator, jaw setting) which also may not be detected with a measurement-based
      approach. Machine log file analysis could also detect performance problems for
      individual MLC leaves which could be masked in the analysis of a measured
      fluence.

PMID- 22955650
TI  - Preclinical assessment of comfort and secure fit of thermobrachytherapy surface
      applicator (TBSA) on volunteer subjects.
AB  - A thermobrachytherapy surface applicator (TBSA) was developed for simultaneous
      heat and brachytherapy treatment of chest wall (CW) recurrence of breast cancer.
      The ability to comfortably secure the applicator over the upper torso relative to
      the CW target throughout treatment is assessed on volunteers. Male and
      postmastectomy female volunteers were enrolled to evaluate applicator secure fit
      to CW. Female subjects with intact breast were also enrolled to assess the
      ability to treat challenging cases. Magnetic resonance (MR) images of volunteers
      wearing a TBSA over the upper torso were acquired once every 15 minutes for 90
      minutes. Applicator displacement over this time period required for treatment
      preplanning and delivery was assessed using MR visible markers. Applicator
      comfort and tolerability were assessed using a questionnaire. Probability
      estimates of applicator displacements were used to investigate dosimetric impact
      for the worst-case variation in radiation source-to-skin distance for 5 and 10 mm
      deep targets spread 17 * 13 cm on a torso phantom. Average and median
      displacements along lateral and radial directions were less than 1.2 mm over 90
      minutes for all volunteers. Maximum lateral and radial displacements were
      measured to be less than 1 and 1.5 mm, respectively, for all CW volunteers and
      less than 2 mm for intact breast volunteers, excluding outliers. No complaint of
      pain or discomfort was reported. Phantom treatment planning for the maximum
      displacement of 2 mm indicated < 10% increase in skin dose with < 5% loss of
      homogeneity index (HI) for -2 mm uniform HDR source displacement. For +2 mm
      uniform displacement, skin dose decreased and HI increased by 20%. The volunteer
      study demonstrated that such large and uniform displacements should be rare for
      CW subjects, and the measured variation is expected to be low for multifraction
      conformal brachytherapy treatment.

PMID- 22955651
TI  - Angular dependence correction of MatriXX and its application to composite dose
      verification.
AB  - We measured the angular dependence of central and off-axis detectors in a 2D
      ionization chamber array, MatriXX, and applied correction factors (CFs) to
      improve the accuracy of composite dose verification of IMRT and VMAT. The MatriXX
      doses were measured with a 10 degrees  step for gantry angles (theta) of 0
      degrees -180 degrees , and a 1 degrees  step for lateral angles of 90 degrees 
      110 degrees  in a phantom, with a 30 * 10 cm2 field for 6 MV and 10 MV photons.
      The MatriXX doses were also calculated under the same conditions by the Monte
      Carlo (MC) algorithm. The CFs for the angular dependence of MatriXX were obtained
      as a function of theta from the ratios of MatriXX-measured doses to MC-calculated
      doses, and normalized at theta = 0 degrees . The corrected MatriXX were validated
      with different fields, various simple plans, and clinical treatment plans. The
      dose distributions were compared with those of MC calculations and film. The
      absolute doses were also compared with ionization chamber and MC-calculated
      doses. The angular dependence of MatriXX showed over-responses of up to 6% and 4%
      at theta = 90 degrees  and under-responses of up to 15% and 11% at 92 degrees ,
      and 8% and 5% at 180 degrees  for 6 MV and 10 MV photons, respectively. At 92
      degrees , the CFs for the off-axis detectors were larger by up to 7% and 6% than
      those for the central detectors for 6 MV and 10 MV photons, respectively, and
      were within 2.5% at other gantry angles. For simple plans, MatriXX doses with
      angular correction were within 2% of those measured with the ionization chamber
      at the central axis and off-axis. For clinical treatment plans, MatriXX with
      angular correction agreed well with dose distributions calculated by the
      treatment planning system (TPS) for gamma evaluation at 3% and 3 mm. The angular
      dependence corrections of MatriXX were useful in improving the measurement
      accuracy of composite dose verification of IMRT and VMAT.

PMID- 22955652
TI  - The energy margin strategy for reducing dose variation due to setup uncertainty
      in intensity modulated proton therapy (IMPT) delivered with distal edge tracking
      (DET).
AB  - Intensity-modulated proton therapy (IMPT) can produce plans with similar target
      dose conformity but lower normal tissue dose than intensity-modulated X-ray
      therapy (IMXT). However, due to the finite range of proton beams in tissue,
      proton therapy treatment plans are usually more sensitive to setup uncertainties
      than X-ray therapy plans. In this work, the energy margin (EM) concept, which was
      initially developed for passive scattering proton therapy, was generalized to
      apply to IMPT treatment planning. The effectiveness of the EM method was
      evaluated on five head-and-neck cancer patients with distal edge tracking (DET)
      treatment plans by comparing the original plans (ORG) without an EM to those with
      an EM. Three beam arrangements were considered: 24 beams delivered over a 360
      degrees  arc, 12 beams delivered over a 180 degrees  arc, and 12 beams delivered
      over two 90 degrees  fan angles. Setup uncertainty was modeled by sampling rigid
      translational shifts from a Gaussian distribution with a mean of 0 mm and
      standard deviation of 2 mm in all directions. Delivered dose distributions for
      all 30 fractions were recalculated using the Geant4 Monte Carlo code. Normalized
      total dose (NTD) for both the CTV and a ring structure surrounding the PTV were
      recorded. The plan quality comparison revealed that EM plans had the same CTV
      coverage but higher dose to the normal tissue than ORG plans. After the simulated
      delivery, ORG plans resulted in more than 3% underdosage to 5% of the CTV volume
      in all three beam arrangements, whereas the EM plans did not. Both ORG and EM
      plans did not produce more than 5% overdose to D2% of the ring structure. The use
      of an EM for IMPT treatment planning can substantially reduce sensitivity of the
      resulting dose distributions to setup uncertainty.

PMID- 22955653
TI  - A phantom study to determine the optimum size of a single collimator for
      shortening the treatment time in CyberKnife stereotactic radiosurgery of
      spherical targets.
AB  - Prolonged treatment execution time is a concern in CyberKnife robotic
      radiosurgery. Beam reduction and node reduction technique, and monitor unit
      optimization methods are adopted to reduce the treatment time. Usage of single
      collimator in the CyberKnife treatment plan can potentially reduce collimator
      exchange time. An optimal single collimator, which yields an acceptable dose
      distribution along with minimum number of nodes, beams, and monitor units, can be
      a versatile alternative for shortening treatment time. The aim of the present
      study is to find the optimal single collimator in CyberKnife treatment planning
      to shorten the treatment time with the acceptable dose distribution. A spherical
      planning target volume PTV1 was drawn in an anthropomorphic head and neck
      phantom. Plans with same treatment goals were generated for all the 12
      collimators independently. D(95%) was selected as the prescribing isodose and the
      prescribed dose was 10 Gy. The plan of the optimal collimator size was evaluated
      for conformity, homogeneity, and dose spillage outside the target. The optimum
      collimator size and the target dimensions were correlated. The study was repeated
      with two other target volumes PTV2 and PTV3 for generalizing the results.
      Collimator sizes just above the diameter of the spherical PTVs were yielding
      least number of nodes and beams with acceptable dose distributions. The
      collimator size of 35 mm is optimum for the PTV1, whose diameter is 31.4 mm.
      Similarly, 50 mm collimator is optimum for PTV2 (diameter= 45.2 mm) and 20 mm
      collimator is optimum for PTV3 (Diameter = 17.3 mm). The total number of monitor
      units is found to reduce with increasing collimator size. Optimal single
      collimator is found to be useful for shortening the treatment time in spherical
      targets. Studies on two clinical targets, (a brain metastasis and a liver
      metastasis cases) show comparable results with the phantom study.

PMID- 22955654
TI  - Investigation of probabilistic optimization for tomotherapy.
AB  - This work builds on a suite of studies related to the 'interplay', or lack
      thereof, for respiratory motion with helical tomotherapy (HT). It helps explain
      why HT treatments without active motion management had clinical outcomes that
      matched positive expectations. An analytical calculation is performed to
      illuminate the frequency range for which interplay-type dose errors could occur.
      Then, an experiment is performed which completes a suite of tests. The experiment
      shows the potential for a stable motion probability distribution function (PDF)
      with HT and respiratory motion. This PDF enables one to use a motion-robust or
      probabilistic optimization to intrinsically include respiratory motion into the
      treatment planning. The reason why HT is robust to respiratory motion is related
      to the beam modulation sampling of the tumor motion. Because active tracking
      based motion management is more complicated for a variety of reasons, HT
      optimization that is robust to motion is a useful alternative for those many
      patients that cannot benefit from active motion management.

PMID- 22955655
TI  - Peripheral dose from megavoltage cone-beam CT imaging for nasopharyngeal
      carcinoma image-guided radiation therapy.
AB  - The growing use of cone-beam computed tomography (CBCT) for IGRT has increased
      concerns over the additional radiation dose to patients. The in-field dose of
      IGRT and the peripheral dose (PD) from kilovoltage CBCT (KV-CBCT) imaging have
      been well quantified. The purpose of this work is to evaluate the peripheral dose
      from megavoltage CBCT (MV-CBCT) imaging for nasopharyngeal carcinoma IGRT, to
      determine the correlation of peripheral dose with MU protocol and imaging field
      size, and to estimate out-of-field organ-at-risk (OAR) dose delivered to
      patients. Measurements of peripheral MV-CBCT doses were made with a 0.65 cm(3)
      ionization chamber placed inside in a specially designed phantom at various
      depths and distances from the imaging field edges. The peripheral dose at
      reference point inside the phantom was measured with the same ionization chamber
      to investigate the linearity between MUs used for MV-CBCT imaging and the PD. The
      peripheral surface doses at the anterior, lateral, and posterior of the phantom
      at various distances from the imaging field edge were also measured with
      thermoluminescent dosimeters (TLDs). Seven nasopharyngeal carcinoma patients were
      selected and scanned before treatment with head-neck protocol, and the peripheral
      surface doses were measured with TLDs placed on the anterior, lateral, and
      posterior surfaces at the axial plane of 15 cm distance from the field edge. The
      measured peripheral doses data in the phantom were utilized to estimate the
      peripheral OAR dose. Peripheral dose from MV-CBCT imaging increased with
      increasing number of MUs used for imaging protocol and with increasing the
      imaging field size. The measured peripheral doses in the phantom decreased as
      distance from the imaging field edges increased. PD also decreased as the depth
      from the phantom surface increased. For the patient PD measurements, the
      anterior, lateral, and posterior surface doses of 15 cm distance from the field
      edge were 2.84 * 10(-2), 1.01 * 10(-2), and 0.78 * 10(-2) cGy/MU, respectively.
      The lens, thyroid, breast, and ovary and testicle, which are outside the
      treatment and imaging fields, were estimated to receive peripheral OAR doses from
      MV-CBCT imaging of 42.4 * 10(-2), 11.9 * 10(-2), 1.4 * 10(-2), 1.0 * 10(-2), and
      0.5 * 10(-2) cGy/MU, respectively. In conclusion, MV-CBCT generates a peripheral
      dose beyond the edge of the MV-CBCT scanning field that is of a similar order of
      magnitude to the peripheral dose from kV-CBCT imaging. In clinic, using the
      smallest number of MUs allowable and reducing MV-CBCT scanning field size without
      compromising acquired image quality is an effective method of reducing the
      peripheral OAR dose received by patients.

PMID- 22955656
TI  - New strategy for automatic tumor segmentation by adaptive thresholding on PET/CT
      images.
AB  - Tumor delineation is a critical aspect in radiotherapy treatment planning and is
      usually performed with the anatomical images of a computed tomography (CT) scan.
      For non-small cell lung cancer, it has been recommended to use functional
      positron emission tomography (PET) images to take into account the biological
      target characteristics. However, today, there is no satisfactory segmentation
      technique for PET images in clinical applications. In the present study, a
      solution to this problem is proposed. The development of the segmentation
      technique is based on the threshold's adjustment directly from patients, rather
      than from phantoms. To this end, two references were chosen: measurements
      performed on CT images of the selected lesions, and histological measurements of
      surgically removed tumors. The inclusion and exclusion criteria were chosen to
      produce references that are assumed to have measured tumor sizes equal to the
      true in vivo tumor sizes. In total, for the two references, 65 lung lesions of 54
      patients referred for FDG-PET/CT exams were selected. For validation,
      measurements of segmented lesions on PET images using this technique were also
      compared to CT and histological measurements. For lesions greater than 20 mm, our
      segmentation technique showed a good estimation of histological measurements
      (mean difference between measured and calculated data equal to -0.8 +/- 9.0%) and
      an acceptable estimation of CT measurements. For lesions smaller than or equal to
      20 mm, the method showed disagreement with the measurements derived from
      histological or CT data. This novel segmentation technique shows high accuracy
      for the lesions with largest axes between 2 and 4.5 cm. However, it does not
      correctly evaluate smaller lesions, likely due to the partial volume effect
      and/or respiratory motions.

PMID- 22955657
TI  - Surface dose reduction from bone interface in kilovoltage X-ray radiation
      therapy: a Monte Carlo study of photon spectra.
AB  - This study evaluated the dosimetric impact of surface dose reduction due to the
      loss of backscatter from the bone interface in kilovoltage (kV) X-ray radiation
      therapy. Monte Carlo simulation was carried out using the EGSnrc code. An
      inhomogeneous phantom containing a thin water layer (0.5-5 mm) on top of a bone
      (thickness = 1 cm) was irradiated by a clinical 105 kVp photon beam produced by a
      Gulmay D3225 X-ray machine. Field sizes of 2, 5, and 10 cm diameter and source-to
      surface distance of 20 cm were used. Surface doses for different phantom
      configurations were calculated using the DOSXYZnrc code. Photon energy spectra at
      the phantom surface and bone were determined according to the phase-space files
      at the particle scoring planes which included the multiple crossers. For
      comparison, all Monte Carlo simulations were repeated in a phantom with the bone
      replaced by water. Surface dose reduction was found when a bone was underneath
      the water layer. When the water thickness was equal to 1 mm for the circular
      field of 5 cm diameter, a surface dose reduction of 6.3% was found. The dose
      reduction decreased to 4.7% and 3.4% when the water thickness increased to 3 and
      5 mm, respectively. This shows that the impact of the surface dose uncertainty
      decreased while the water thickness over the bone increased. This result was
      supported by the decrease in relative intensity of the lower energy photons in
      the energy spectrum when the water layer was with and over the bone, compared to
      without the bone. We concluded that surface dose reduction of 7.8%-1.1% was found
      when the water thickness increased from 0.5-5 mm for circular fields with
      diameters ranging from 2-10 cm. This decrease of surface dose results in an
      overestimation of prescribed dose at the patient's surface, and might be a
      concern when using kV photon beam to treat skin tumors in sites such as forehead,
      chest wall, and kneecap.

PMID- 22955658
TI  - Errors introduced by dose scaling for relative dosimetry.
AB  - Some dosimeters require a relationship between detector signal and delivered
      dose. The relationship (characteristic curve or calibration equation) usually
      depends on the environment under which the dosimeters are manufactured or stored.
      To compensate for the difference in radiation response among different batches of
      dosimeters, the measured dose can be scaled by normalizing the measured dose to a
      specific dose. Such a procedure, often called "relative dosimetry", allows us to
      skip the time-consuming production of a calibration curve for each irradiation.
      In this study, the magnitudes of errors due to the dose scaling procedure were
      evaluated by using the characteristic curves of BANG3 polymer gel dosimeter,
      radiographic EDR2 films, and GAFCHROMIC EBT2 films. Several sets of calibration
      data were obtained for each type of dosimeters, and a calibration equation of one
      set of data was used to estimate doses of the other dosimeters from different
      batches. The scaled doses were then compared with expected doses, which were
      obtained by using the true calibration equation specific to each batch. In
      general, the magnitude of errors increased with increasing deviation of the dose
      scaling factor from unity. Also, the errors strongly depended on the difference
      in the shape of the true and reference calibration curves. For example, for the
      BANG3 polymer gel, of which the characteristic curve can be approximated with a
      linear equation, the error for a batch requiring a dose scaling factor of 0.87
      was larger than the errors for other batches requiring smaller magnitudes of dose
      scaling, or scaling factors of 0.93 or 1.02. The characteristic curves of EDR2
      and EBT2 films required nonlinear equations. With those dosimeters, errors larger
      than 5% were commonly observed in the dose ranges of below 50% and above 150% of
      the normalization dose. In conclusion, the dose scaling for relative dosimetry
      introduces large errors in the measured doses when a large dose scaling is
      applied, and this procedure should be applied with special care.

PMID- 22955659
TI  - Implementation and evaluation of an end-to-end IGRT test.
AB  - The goal of this work was to develop and evaluate an end-to-end test for
      determining and verifying image-guided radiation therapy setup accuracy relative
      to the radiation isocenter. This was done by placing a cube phantom with a
      central tungsten sphere directly on the treatment table and offset from isocenter
      either by 5.0 mm in the longitudinal, lateral, and vertical dimensions or by a
      random amount. A high-resolution cone-beam CT image was acquired and aligned with
      the tungsten sphere in the reference CT image. The table was shifted per this
      alignment, and megavoltage anterior-posterior and lateral images were acquired
      with the electronic portal imaging device. Agreement between the radiation
      isocenter (based on the MV field) and the center of the sphere (i.e., the
      alignment point based on kV imaging) was determined for each image via Winston
      Lutz analysis. This procedure was repeated 10 times to determine short-term
      reproducibility, and then repeated daily for 51 days in a clinical setting. The
      short-term reproducibility test yielded a mean 3D vector displacement of 0.9 +/-
      0.15 mm between the imaging-based isocenter and the radiation isocenter, with a
      maximum displacement of 1.1 mm. The clinical reproducibility test yielded a mean
      displacement of1.1 +/- 0.4 mm with a maximum of 2.0 mm when the cube was offset
      by 5.0 mm, and a mean displacement of 0.9 +/- 0.3 mm with a maximum of 1.8 mm
      when the cube was offset by a random amount. These differences were observed in
      all directions and were independent of the magnitude of the couch shift. This
      test was quick and easy to implement clinically and highlighted setup
      inaccuracies in an image-guided radiation therapy environment.

PMID- 22955660
TI  - Effectiveness of a novel gas-release endorectal balloon in the removal of rectal
      gas for prostate proton radiation therapy.
AB  - Endorectal balloons (ERBs) are routinely used in prostate proton radiation
      therapy to immobilize the prostate and spare the rectal wall. Rectal gas can
      distend the rectum and displace the prostate even in the presence of ERBs. The
      purpose of this work was to quantify the effects an ERB with a passive gas
      release conduit had on the incidence of rectal gas. Fifteen patients who were
      treated with a standard ERB and 15 with a gas-release ERB were selected for this
      retrospective study. Location and cross-sectional area of gas pockets and the
      fraction of time they occurred on 1133 lateral kilovoltage (kV) images were
      analyzed. Gas locations were classified as trapped between the ERB and anterior
      rectal wall, between the ERB and posterior rectal wall, or superior to the ERB.
      For patients using the standard ERB, gas was found in at least one region in
      45.8% of fractions. Gas was trapped in the anterior region in 37.1% of fractions,
      in the posterior region in 5.0% of fractions, and in the sigmoid region in 9.6%
      of fractions. For patients using the ERB with the gas-release conduit, gas was
      found in at least one region in 19.7% of fractions. Gas was trapped in the
      anterior region in 5.6% of fractions, in the posterior region in 8.3% of
      fractions, and in the sigmoid region in 7.4% of fractions. Both the number of
      fractions with gas in the anterior region and the number of fractions with gas in
      at least one region were significantly higher in the former group than in the
      latter. The cross-sectional area of trapped gas did not differ between the two
      groups. Thus gas-release balloon can effectively release gas, and may be able to
      improve clinical workflow by reducing the need for catheterization.

PMID- 22955661
TI  - Comparison of Epson scanner quality for radiochromic film evaluation.
AB  - Epson Desktop scanners have been quoted as devices which match the
      characteristics required for the evaluation of radiation dose exposure by
      radiochromic films. Specifically, models such as the 10000XL have been used
      successfully for image analysis and are recommended by ISP for dosimetry
      purposes. This note investigates and compares the scanner characteristics of
      three Epson desktop scanner models including the Epson 10000XL, V700, and V330.
      Both of the latter are substantially cheaper models capable of A4 scanning. As
      the price variation between the V330 and the 10000XL is 20-fold (based on
      Australian recommended retail price), cost savings by using the cheaper scanners
      may be warranted based on results. By a direct comparison of scanner uniformity
      and reproducibility we can evaluate the accuracy of these scanners for
      radiochromic film dosimetry. Results have shown that all three scanners can
      produce adequate scanner uniformity and reproducibility, with the inexpensive
      V330 producing a standard deviation variation across its landscape direction of
      0.7% and 1.2% in the portrait direction (reflection mode). This is compared to
      the V700 in reflection mode of 0.25% and 0.5% for landscape and portrait
      directions, respectively, and 0.5% and 0.8% for the 10000XL. In transmission
      mode, the V700 is comparable in reproducibility to the 10000XL for portrait and
      landscape mode, whilst the V330 is only capable of scanning in the landscape
      direction and produces a standard deviation in this direction of 1.0% compared to
      0.6% (V700) and 0.25% (10000XL). Results have shown that the V700 and 10000XL are
      comparable scanners in quality and accuracy with the 10000XL obviously capable of
      imaging over an A3 area as opposed to an A4 area for the V700. The V330 scanner
      produced slightly lower accuracy and quality with uncertainties approximately
      twice as much as the other scanners. However, the results show that the V330 is
      still an adequate scanner and could be used for radiation dosimetry purposes. As
      such, if budgetary requirements are limited, the V700 scanner would be the
      recommended option at a price eight times cheaper than the 10000XL; however, the
      V330 produces adequate results at a price which is 2.5 times cheaper again. This
      may be a consideration for smaller institutions or individuals working with
      radiochromic film dosimetry.

PMID- 22955662
TI  - Radiation dose and physical image quality in 128-section dual-source computed
      tomographic coronary angiography: a phantom study.
AB  - One-hundred-and-twenty-eight-section dual X-ray source computed tomography (CT)
      systems have been introduced into clinical practice and have been shown to
      increase temporal resolution. Higher temporal resolution allows low-dose spiral
      mode at a high pitch factor during CT coronary angiography. We evaluated
      radiation dose and physical image qualities in CT coronary angiography by
      applying high-pitch spiral, step-and-shoot, and low-pitch spiral modes to
      determine the optimal acquisition mode for clinical situations. An
      anthropomorphic phantom, small dosimeters, a calibration phantom, and a microdisc
      phantom were used to evaluate the radiation doses absorbed by thoracic organs,
      noise power spectrums, in-plane and z-axis modulation transfer functions, slice
      sensitivity profiles, and number of artifacts for the three acquisition modes.
      The high-pitch spiral mode had the advantage of a small absorbed radiation dose,
      but provided low image quality. The low-pitch spiral mode resulted in a high
      absorbed radiation dose of approximately 200 mGy for the heart. Although the
      absorbed radiation dose was lower in the step-and-shoot mode than in the low
      pitch spiral mode, the noise power spectrum was inferior. The quality of the in
      plane modulation transfer function differed, depending on spatial frequency.
      Therefore, the step-and-shoot mode should be applied initially because of its low
      absorbed radiation dose and superior image quality.

PMID- 22955663
TI  - Monte Carlo modeling of a Novalis Tx Varian 6 MV with HD-120 multileaf
      collimator.
AB  - A Monte Carlo model of the Novalis Tx linear accelerator equipped with high
      definition multileaf collimator (HD-120 HD-MLC) was commissioned using ionization
      chamber measurements in water. All measurements in water were performed using a
      liquid filled ionization chamber. Film measurements were made using EDR2 film in
      solid water. Open rectangular fields defined by the jaws or the HD-MLC were used
      for comparison against measurements. Furthermore, inter- and intraleaf leakage
      calculated by the Monte Carlo model was compared against film measurements. The
      statistical uncertainty of the Monte Carlo calculations was less than 1% for all
      simulations. Results for all regular field sizes show an excellent agreement with
      commissioning data (percent depth-dose curves and profiles), well within 1% of
      difference in the relative dose and 1 mm distance to agreement. The computed
      leakage through HD-MLCs shows good agreement with film measurements. The Monte
      Carlo model developed in this study accurately represents the new Novalis Tx
      Varian linac with HD-MLC and can be used for reliable patient dose calculations.

PMID- 22955664
TI  - The Radiological Physics Center's standard dataset for small field size output
      factors.
AB  - Delivery of accurate intensity-modulated radiation therapy (IMRT) or stereotactic
      radiotherapy depends on a multitude of steps in the treatment delivery process.
      These steps range from imaging of the patient to dose calculation to machine
      delivery of the treatment plan. Within the treatment planning system's (TPS) dose
      calculation algorithm, various unique small field dosimetry parameters are
      essential, such as multileaf collimator modeling and field size dependence of the
      output. One of the largest challenges in this process is determining accurate
      small field size output factors. The Radiological Physics Center (RPC), as part
      of its mission to ensure that institutions deliver comparable and consistent
      radiation doses to their patients, conducts on-site dosimetry review visits to
      institutions. As a part of the on-site audit, the RPC measures the small field
      size output factors as might be used in IMRT treatments, and compares the
      resulting field size dependent output factors to values calculated by the
      institution's treatment planning system (TPS). The RPC has gathered multiple
      small field size output factor datasets for X-ray energies ranging from 6 to 18
      MV from Varian, Siemens and Elekta linear accelerators. These datasets were
      measured at 10 cm depth and ranged from 10 * 10 cm(2) to 2 * 2 cm(2). The field
      sizes were defined by the MLC and for the Varian machines the secondary jaws were
      maintained at a 10 * 10 cm(2). The RPC measurements were made with a micro-ion
      chamber whose volume was small enough to gather a full ionization reading even
      for the 2 * 2 cm(2) field size. The RPC-measured output factors are tabulated and
      are reproducible with standard deviations (SD) ranging from 0.1% to 1.5%, while
      the institutions' calculated values had a much larger SD range, ranging up to
      7.9% [corrected].The absolute average percent differences were greater for the 2
      * 2 cm(2) than for the other field sizes. The RPC's measured small field output
      factors provide institutions with a standard dataset against which to compare
      their TPS calculated values. Any discrepancies noted between the standard dataset
      and calculated values should be investigated with careful measurements and with
      attention to the specific beam model.

PMID- 22955665
TI  - Determination of optimal fiducial marker across image-guided radiation therapy
      (IGRT) modalities: visibility and artifact analysis of gold, carbon, and polymer
      fiducial markers.
AB  - The purpose of this study was to evaluate the visibility and artifact created by
      gold, carbon, and polymer fiducial markers in a simple phantom across computed
      tomography (CT), kilovoltage (kV), and megavoltage (MV) linear accelerator
      imaging and MV tomotherapy imaging. Three types of fiducial markers (gold,
      carbon, and polymer) were investigated for their visibility and artifacts in
      images acquired with various modalities and with different imaging parameters
      (kV, mAs, slice thickness). The imaging modalities include kV CT, 2D linac-based
      kilovoltage and megavoltage X-ray imaging systems, kV cone-beam CT, and normal
      and fine tomotherapy imaging. The images were acquired on a phantom constructed
      using Superflab bolus in which markers of each type were inserted into the center
      layer. The visibility and artifacts produced by each marker were assessed
      qualitatively and quantitatively. All tested markers could be identified clearly
      on the acquired CT and linac-based kV images; gold markers demonstrated the
      highest contrast. On the CT images, gold markers produced a significant artifact,
      while no artifacts were observed with polymer markers. Only gold markers were
      visible when using linac-based MV and tomotherapy imaging. For linac-based kV
      images, the contrast increased with kV and mAs values for all the markers, with
      the gold being the most pronounced. On CT images, the contrast increased with kV
      for the gold markers, while decreasing for the polymer and carbon marker. With
      the bolus phantom used, we found that when kV imaging-based treatment
      verification equipment is available, polymer and carbon markers may be the
      preferred choice for target localization and patient treatment positioning
      verification due to less image artifacts. If MV imaging will be the sole modality
      for positioning verification, it may be necessary to use gold markers despite the
      artifacts they create on the simulation CT images.

PMID- 22955666
TI  - Editorial: Peer review vs. open posting.

PMID- 22955667
TI  - Seed particle-enabled acoustic trapping of bacteria and nanoparticles in
      continuous flow systems.
AB  - Acoustic trapping of sub-micron particles can allow enrichment and purification
      of small-sized and low-abundance microorganisms. In this paper, we investigate
      the dependency of the ability to capture sub-micron particles on the particle
      concentration. Based on the findings, it is demonstrated that seed particles can
      be introduced to acoustic trapping, to enable capture of low-abundance sub-micron
      particles. Without using seed particles, continuous enrichment of 490 nm
      polystyrene particles is demonstrated in a rectangular capillary with a locally
      generated acoustic field at high particle concentrations, i.e. above 1% wt.
      Trapping of sub-micron particles at significantly lower concentrations was
      subsequently accomplished by seeding 10-12 micrometer-sized particles in the
      acoustic trap prior to the sub-micron particle capture. Furthermore, the new
      seeded-particle-aided acoustic trapping technique was employed for the continuous
      enrichment of bacteria (E. coli) with a capture efficiency of 95%. Finally, seed
      particle assisted acoustic trapping and enrichment is demonstrated for polymer
      based particles down to 110 nm in diameter.

PMID- 22955668
TI  - Ethnic variability in the allelic distribution of pharmacogenes between Korean
      and other populations.
AB  - OBJECTIVE: We examined the differences in allele frequencies for pharmacogenes
      among the Korean (KOR), Chinese (CHB), Japanese (JPT), Caucasian (CEU), and
      Nigerian (YRI) populations. METHODS: Fifty-seven pharmacogenes were selected from
      the imputed Korean Association REsource and HapMap databases. Minor allele
      frequencies were analyzed using the sample size-modified single nucleotide
      polymorphism-specific fixation index (FST) and the chi-test with Bonferroni's
      correction. Geneset analysis was also carried out to identify pharmacogenes that
      have significantly different allele frequencies among the various populations
      tested. RESULTS: The KOR population was the most divergent group from the YRI
      population (FST: 0.079) but very similar to the CHB and JPT populations (FST:
      0.003). VKORC1 showed a large population divergence in the KOR-YRI (0.439)
      comparison. CYP3A4 was also highly divergent in the KOR-YRI (FST: 0.361)
      comparison. The calcium signaling pathway gene set was divergent in all pairwise
      population comparisons. CONCLUSION: In terms of the 57 pharmacogenes studied,
      there were no significant differences among the KOR, CHB, and JPT populations.
      However, the YRI and CEU populations were significantly differentiated from the
      three Eastern Asian groups. Future pharmacogenomics studies can utilize the
      polymorphisms identified in this study, as these variants may have important
      implications for the selection of highly informative single nucleotide
      polymorphisms for future clinical trials.

PMID- 22955669
TI  - Assessing the impact of a heparin-induced thrombocytopenia protocol on patient
      management, outcomes and cost.
AB  - Establishing the diagnosis of heparin induced thrombocytopenia (HIT) is
      challenging as laboratory tests for HIT vary in specificity and availability. As
      HIT suspicion far exceeds confirmation of diagnosis, overtreatment is an emerging
      concern. This pilot study evaluated the impact of a HIT Recognition and
      Management Protocol on direct thrombin inhibitor (DTI) prescribing, outcomes, and
      cost. The primary endpoint was DTI cessation within 12 hours of receipt of
      negative HIT serology. An observational cohort study using a pre-post design was
      performed. Sixty-one patients were in the pre-period (before implementation) and
      46 in the post-period (after implementation). DTI therapy was discontinued within
      12 hours of negative serology in 19.4% of pre-period patients compared to 40% of
      post-period patients, p=.058. DTI therapy was discontinued within 24 hours of
      receipt of a negative PF4/heparin ELISA more often in the post-period; 7/23
      (30.4%) pre-period patients versus 16/26 (61.5%) post-period patients, p <0.05.
      Protocol implementation resulted in a significant improvement in timely
      initiation of DTI therapy (within 12 hours of HIT antibody testing) in those with
      a moderate to high suspicion of HIT; 8/31 (25.8%) of pre-period patients versus
      24/31 (77.4%) of post-period patients, p <0.0001. Thrombotic events occurred in
      significantly more patients in the pre-period as compared to the post-period;
      21/61 (34.4%) versus 6/46 (13%), respectively, p = 0.01. Major bleeding was
      reduced by 6.6 % after protocol implementation. The projected annual cost savings
      from decreased inappropriate DTI use was over $450,000. Protocol implementation
      had a positive impact on DTI prescribing, outcomes and cost.

PMID- 22955670
TI  - Enantioselective separation and simultaneous determination of fenarimol and
      nuarimol in fruits, vegetables, and soil by liquid chromatography-tandem mass
      spectrometry.
AB  - A method for simultaneous enantioselective determination of fenarimol and
      nuarimol in apple, grape, cucumber, tomato, and soil was developed using liquid
      chromatography-tandem mass spectrometry. The enantioseparation results of the two
      fungicides through three different cellulose-based chiral columns are discussed.
      The influence of column temperature on the resolution of the enantiomers of the
      two fungicides was examined. Complete enantioseparation of the two fungicides'
      enantiomers was obtained on a cellulose tris(4-methylbenzoate) column (Lux
      Cellulose-3) at 25  degrees C using methanol and 0.1 % formic acid solution
      (80:20, v/v) as mobile phase. The linearity, matrix effect, recovery, and
      precision were evaluated. Good linearity was obtained over the concentration
      range of 1-500 MUg L(-1) for each enantiomer in the standard solution and sample
      matrix calibration solution. There was no significant matrix effect in apple,
      grape, cucumber, or tomato samples, but signal suppression was typically observed
      with the soil extracts. The mean recoveries, repeatability, and reproducibility
      were 76.5-103 %, 2.1-9.0 %, and 4.2-11.8 %, respectively. The limit of
      quantification for enantiomers of the two fungicides in fruits, vegetables and
      soil was 5 MUg kg(-1). Moreover, the absolute configuration of the enantiomers of
      fenarimol and nuarimol was determined from a combination of experimentally
      determined and predicted electronic circular dichroism spectra.

PMID- 22955671
TI  - Single nucleotide polymorphism detection by optical DNA-based sensing coupled
      with whole genomic amplification.
AB  - The work presented here deals with the optimization of a strategy for detection
      of single nucleotide polymorphisms based on surface plasmon resonance imaging.
      First, a sandwich-like assay was designed, and oligonucleotide sequences were
      computationally selected in order to study optimized conditions for the detection
      of the rs1045642 single nucleotide polymorphism in the gene ABCB1. Then the
      strategy was optimized on a surface plasmon resonance imaging biosensor using
      synthetic DNA sequences in order to evaluate the best conditions for the
      detection of a single mismatching base. Finally, the assay was tested on DNA
      extracted from human blood which was subsequently amplified using a whole genome
      amplification kit. The direct detection of the polymorphism was successfully
      achieved. The biochip was highly regenerable and reusable for up to 20
      measurements. Furthermore, coupling these promising results with the multiarray
      assay, we can foresee applying this biosensor in clinical research extended to
      concurrent analysis of different polymorphisms.

PMID- 22955672
TI  - Ensembles of nanoelectrodes modified with gold nanoparticles: characterization
      and application to DNA-hybridization detection.
AB  - A new method to increase the active area (A(act)) of nanoelectrode ensembles
      (NEEs) is described. To this aim, gold nanoparticles (AuNPs) are immobilized onto
      the surface of NEEs using cysteamine as a cross-linker able to bind the AuNPs to
      the heads of the nanoelectrodes to obtain the so-called AuNPs-NEEs. The analysis
      of the cyclic voltammograms recorded in pure supporting electrolyte showed that
      the presence of the nanoparticles reflects in an, approximately, ten-times
      increase in the electrochemically active area of the ensemble. The measurement of
      the amount of electroactive polyoxometalates, which can be adsorbed on the gold
      surface of NEEs vs. AuNPs-NEEs, confirmed a significant increase of active area
      for the latter. These evidences indicate that there is a good electronic
      connection between the AuNPs and the underlying nanoelectrodes. The possibility
      to exploit AuNPs-NEEs for biosensing application was tested for the case of DNA
      hybridization detection. After immobilization on the gold surface of AuNPs-NEEs
      of a thiolated single-stranded DNA, the hybridization with complementary
      sequences labeled with glucose oxidase (GOx) was performed. The detection of the
      hybridization was achieved by adding to the electrolyte solution the GOx
      substrate (i.e., glucose) and a suitable redox mediator, namely the
      (ferrocenylmethyl) trimethylammonium (FA(+)) cation; when the hybridization
      occurs, an electrocatalytic increase of the oxidation current of FA(+) is
      recorded. Comparison of electrocatalytic current recorded at DNA modified NEEs
      and AuNPs-NEEs indicate, for the latter, a significant increase in sensitivity in
      the detection of the DNA-hybridization event.

PMID- 22955673
TI  - Sensitive, robust and automated protein analysis of cell differentiation and of
      primary human blood cells by intact cell MALDI mass spectrometry biotyping.
AB  - Intact cell mass spectrometry biotyping, a collection of methods for
      classification of cells based on mass spectrometric fingerprints, is an
      established method in clinical and environmental microbiology. It has recently
      also been applied to the investigation of mammalian cells including primary blood
      cells and cultured cells. However, few automated procedures suitable for higher
      throughput and little analytical standardization of mammalian biotyping
      approaches have been reported so far. Here, we present a novel automated method
      that robustly classifies as few as 250 cells per spot. Automatically acquired
      cell fingerprints from cultured and primary cells show high technical (R > 0.95)
      and biological reproducibility (R = 0.83-0.96), with a median peak variance below
      12 %. Ion suppression is shown to be a major concern at higher cell numbers and
      needs to be carefully monitored. We demonstrate that intact cell mass
      spectrometric signatures of different cell lines start to resemble each other at
      higher trifluoroacetic acid (TFA) concentrations and that therefore low
      concentrations of TFA in the matrix solution are preferred. We show that in vitro
      differentiation of HL-60 cells into a neutrophil-like phenotype can be rapidly
      and robustly monitored. We utilize the method for global analysis of person-to
      person differences in mass spectral signatures of intact polymorphonuclear
      neutrophils and monocytes obtained from healthy volunteers. Our data suggest that
      automated MALDI mass spectrometry cell biotyping could be a useful complementary
      approach in clinical cell analysis.

PMID- 22955674
TI  - Determination of perfluoroalkyl carboxylic, sulfonic, and phosphonic acids in
      food.
AB  - A sensitive and accurate method was developed and validated for simultaneous
      analysis of perfluoroalkyl carboxylic acids, sulfonic acids, and phosphonic acids
      (PFPAs) at low picograms per gram concentrations in a variety of food matrices.
      The method employed extraction with acetonitrile/water and cleanup on a mixed
      mode co-polymeric sorbent (C8 + quaternary amine) using solid-phase extraction.
      High-performance liquid chromatographic separation was achieved on a C18 column
      using a mobile phase gradient containing 5 mM 1-methyl piperidine for optimal
      chromatographic resolution of PFPAs. A quadrupole time-of-flight high-resolution
      mass spectrometer operating in negative ion mode was used as detector. Method
      detection limits were in the range of 0.002 to 0.02 ng g(-1) for all analytes.
      Sample preparation (extraction and cleanup) recoveries at a spiking level of 0.1
      ng g(-1) to a baby food composite were in the range of 59 to 98 %. A strong
      matrix effect was observed in the analysis of PFPAs in food extracts, which was
      tentatively assigned to sorption of PFPAs to the injection vial in the solvent
      based calibration standard. The method was successfully applied to a range of
      different food matrices including duplicate diet samples, vegetables, meat, and
      fish samples.

PMID- 22955675
TI  - Osteochondral autograft transplantation for juvenile osteochondritis dissecans of
      the knee: a series of twelve cases.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical outcomes of
      osteochondral autograft transplantation (OAT) for juvenile osteochondritis
      dissecans (JOCD) lesions of the knee, especially time to return to sports.
      METHODS: Twelve knee JOCD lesions with OCD grade 3 and 4 categorised by magnetic
      resonance imaging (MRI) were treated with OAT. Nine male and two female
      skeletally immature patients averaging 13.7 years old were included. The OCD
      lesions were assessed arthroscopically and then fixed in situ using multiple
      osteochondral plugs harvested under fluoroscopy from the distal femoral condyle
      without damaging the physis. International Cartilage Repair Society (ICRS) score
      and Lysholm score were assessed pre- and postoperatively. RESULTS: After a mean
      follow-up of 26.2 +/- 15.1 months, the International Knee Documentation Committee
      (IKDC) subjective score significantly improved (p < 0.01). According to the IKDC
      score, objective assessment showed that ten of 12 (83 %) had excellent results
      (score: A) after OAT and significantly improved (p < 0.01). Based on ICRS
      criteria, results were satisfactory in all patients. No patients experienced
      complications at the graft harvest site. All patients returned to their previous
      level of athletic activity at an average of 5.7 months after the surgery.
      CONCLUSIONS: OAT for JOCD of the knee provided satisfactory results in all
      patients at a mean follow-up of 26.2 months.

PMID- 22955676
TI  - Minimally invasive percutaneous osteosynthesis for proximal humeral shaft
      fractures with the PHILOS through the deltopectoral approach.
AB  - PURPOSE: The aim of this study was to evaluate clinical outcomes and
      complications following minimally invasive plate osteosynthesis (MIPO) with the
      proximal humeral internal locking system (PHILOS) for treating proximal humeral
      shaft fracture through the deltopectoral approach. METHODS: Between November 2008
      and March 2010, 74 patients with unilateral proximal humeral shaft fractures were
      treated using the MIPO technique with the PHILOS through the deltopectoral
      approach. Patients received an average follow-up of 16.9 (range, 12-24) months,
      and the final follow-up included anteroposterior and lateral imaging and
      recording of postoperative complications. The Constant-Murley shoulder score was
      used to evaluate function. RESULTS: No intraoperative complications occurred.
      Postoperative complications included subacromial impingement in four patients.
      There was no deep infection, neurovascular damage, breakage or implant loosening.
      All fractures united in an average time of 17.4 (15-25) weeks. In terms of
      function, the Constant-Murley score was 85.8 points on average (range, 67-100).
      The range of motion of the involved shoulder was satisfactory, and pain-free in
      83.8 % of patients. CONCLUSIONS: Using the MIPO technique with the PHILOS through
      the deltopectoral approach is a valid and safe method of treating proximal
      humeral shaft fractures.

PMID- 22955677
TI  - A minimal cytomegalovirus intron A variant can improve transgene expression in
      different mammalian cell lines.
AB  - The expression enhancement by cytomegalovirus promoter and different intron A
      (IA) variants were evaluated in CHO-K1, HepG2, HEK-293 and COS-7 cells by
      assessing the levels of luciferase activity. This data along with mRNA levels
      measurement indicated that the construct harboring an IA variant with a 200
      nucleotide deletion (Delta200) had the greatest impact on increasing luciferase
      expression among all constructs evaluated. Based on these results, we redesigned
      pCMV-IA variants and cloned them into plasmids expressing a humanized antibody.
      These plasmids were then used to transfect CHO-K1 cells. Production of the
      antibody was not augmented with the Delta200 promoter variant. The 600-nucleotide
      deletion (Delta600) and whole IA promoter variants expressed similar levels of
      the recombinant protein. These data indicate that the IA-based enhanced
      expression of transgenes depends on a small region within the intron.

PMID- 22955678
TI  - Myosin-cross-reactive antigens from four different lactic acid bacteria are fatty
      acid hydratases.
AB  - The 67 kDa myosin-cross-reactive antigen (MCRA) is a member of the MCRA family of
      proteins present in a wide range of bacteria and was predicted to have fatty acid
      isomerase function. We have now characterised the catalytic activity of MCRAs
      from four LAB stains, including Lactobacillus rhamnosus LGG, L. plantarum ST-III,
      L. acidophilus NCFM and Bifidobacterium animalis subsp. lactis BB-12. MCRA genes
      from these strains were cloned and expressed in Escherichia coli, and the
      recombinant protein function was analysed with lipid profiles by GC-MS. The four
      MCRAs catalysed the conversion of linoleic acid and oleic acid to their
      respective 10-hydroxy derivatives, which suggests that MCRA proteins catalyse the
      first step in conjugated linoleic acid production. This is the first report of
      MCRA from L. rhamnosus with such catalytic function.

PMID- 22955679
TI  - Production of poly(beta-L-malic acid) (PMA) from agricultural biomass substrates
      by Aureobasidium pullulans.
AB  - For the first time the production of poly(beta-L -malic acid) (PMA) has been
      achieved using agricultural biomass substrates by the yeast-like fungus
      Aureobasidium pullulans. Strains NRRL Y-2311-1, NRRL 50382, NRRL 50383, and NRRL
      50384, representing diverse isolation sources and phylogenetic clades, produced
      PMA from alkaline H(2)O(2)-pretreated corn fiber and wheat straw as sole carbon
      sources. Pretreated wheat straw was better than pretreated corn fiber, and strain
      NRRL 50383 gave the highest overall yields of PMA. The addition of CaCO(3) plus
      supplementary hydrolytic enzymes enhanced PMA production. Four basal media were
      compared for PMA production, and the best was found to be a N-limited pullulan
      production medium (PM). In this medium, PMA production took place during growth
      limitation. Under optimal conditions, strain NRRL 50383 produced more than 20 g
      PMA/l from 5 % (w/v) pretreated wheat straw in PM with 3 % (w/v) CaCO(3) and
      supplementary enzymes.

PMID- 22955680
TI  - Overexpression of maize anthocyanin regulatory gene Lc affects rice fertility.
AB  - Seventeen independent transgenic rice plants with the maize anthocyanin
      regulatory gene Lc under control of the CaMV 35S promoter were obtained and
      verified by molecular identification. Ten plants showed red spikelets during
      early development of florets, and the degenerate florets were still red after
      heading. Additionally, these plants exhibited intense pigmentation on the surface
      of the anther and the bottom of the ovary. They were unable to properly bloom and
      were completely sterile. Following pollination with normal pollen, these plants
      yielded red caryopses but did not mature normally. QRT-PCR analysis indicated
      that mRNA accumulation of the CHS-like gene encoding a chalcone synthase-related
      protein was increased significantly in the sterile plant. This is the first
      report to suggest that upregulation of the CHS gene expression may result in rice
      sterility and affect the normal development of rice seeds.

PMID- 22955681
TI  - Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of
      the transient [myoglobin, cytochrome b5] complex.
AB  - Formation of a transient [myoglobin (Mb), cytochrome b(5) (cyt b(5))] complex is
      required for the reductive repair of inactive ferri-Mb to its functional ferro-Mb
      state. The [Mb, cyt b(5)] complex exhibits dynamic docking (DD), with its cyt
      b(5) partner in rapid exchange at multiple sites on the Mb surface. A triple
      mutant (Mb(3M)) was designed as part of efforts to shift the electron-transfer
      process to the simple docking (SD) regime, in which reactive binding occurs at a
      restricted, reactive region on the Mb surface that dominates the docked ensemble.
      An electrostatically-guided brownian dynamics (BD) docking protocol was used to
      generate an initial ensemble of reactive configurations of the complex between
      unrelaxed partners. This ensemble samples a broad and diverse array of heme-heme
      distances and orientations. These configurations seeded all-atom constrained
      molecular dynamics simulations (MD) to generate relaxed complexes for the
      calculation of electron tunneling matrix elements (T(DA)) through tunneling
      pathway analysis. This procedure for generating an ensemble of relaxed complexes
      combines the ability of BD calculations to sample the large variety of available
      conformations and interprotein distances, with the ability of MD to generate the
      atomic level information, especially regarding the structure of water molecules
      at the protein-protein interface, that defines electron-tunneling pathways. We
      used the calculated T(DA) values to compute ET rates for the [Mb(wt), cyt b(5)]
      complex and for the complex with a mutant that has a binding free energy
      strengthened by three D/E -> K charge-reversal mutations, [Mb(3M), cyt b(5)]. The
      calculated rate constants are in agreement with the measured values, and the
      mutant complex ensemble has many more geometries with higher T(DA) values than
      does the wild-type Mb complex. Interestingly, water plays a double role in this
      electron-transfer system, lowering the tunneling barrier as well as inducing
      protein interface remodeling that screens the repulsion between the negatively
      charged propionates of the two hemes.

PMID- 22955682
TI  - [The use of frozen sections in the handling of soft tissue tumors].
AB  - Due to the multiplicity of localizations and entities, handling of soft tissue
      tumors is a very challenging subject requiring intensive interdisciplinary
      collaboration. With respect to the use of intraoperative frozen sections, the
      following facts are of special relevance: 1) the usual criteria for malignancy,
      such as infiltrative growth and high mitotic rate are only restrictedly
      applicable to soft tissue tumors. 2) Correct diagnosis of the tumor entity often
      requires not only the use of immunohistochemistry but also the identification of
      genetic alterations by the polymerase chain reaction and/or fluorescence in situ
      hybridization. In many centres, 14G core biopsies taken from different tumor
      areas represent the preferred method for a diagnostic biopsy. Apart from
      cryocollection additional frozen section investigations are used especially in
      case of open biopsies for quality control of the submitted material or in cases
      of excision biopsies to ascertain a highly probable radiological diagnosis. The
      use of intraoperative frozen sections to clarify the resection margins is
      generally undisputed but should definitely be restricted to centres specialized
      and experienced in the handling of soft tissue tumors.

PMID- 22955685
TI  - Acute stent thrombosis after a "stroll for fresh air". A case of the smoking gun.
AB  - We present a case of a patient who underwent a percutaneous coronary intervention
      and excused himself for some "fresh air". He subsequently developed acute stent
      thrombosis. We discuss the contribution of acute cigarette smoking to this
      serious complication after stent implantation.

PMID- 22955686
TI  - Successful radiofrequency catheter ablation of atrioventricular nodal reentrant
      tachycardia in a patient with dextrocardia and situs inversus.

PMID- 22955687
TI  - Noncompaction cardiomyopathy. Is it more than noncompaction?
AB  - Noncompaction cardiomyopathy, a rare congenital cardiomyopathy, is characterized
      by increased trabeculation in one or more segments of the ventricle. The
      coexistence of other cardiac anomalies such as coronary-cameral fistula, bicuspid
      aortic valve, ventricular septal defect, patent ductus arteriosus and
      bradyarrhythmias make noncompaction cardiomyopathy resemble the reptile heart.
      The defect in myocardial compaction and the frequently seen accompanying
      anomalies may share a common causative factor during embryogenesis.

PMID- 22955688
TI  - Platelet distribution width and saphenous vein disease in patients after CABG.
      Association with graft occlusion.
AB  - OBJECTIVE: Platelets are involved in the pathogenesis of atherosclerosis. The
      inflammatory process in atherosclerosis may cause an increase in red blood cell
      distribution width (RDW) and platelet distribution width (PDW) values. Therefore,
      in this study we aimed to investigate whether PDW and RDW are associated with the
      patency of saphenous vein graft in patients at least 1 year after coronary artery
      bypass graft (CABG) surgery. METHODS: Patients who had undergone CABG surgery at
      least 1 year previously with at least one saphenous vein graft were included in
      the study population. Patients were referred to cardiac catheterization for
      stable anginal symptoms or positive stress test results. Before coronary
      angiography, all patients referred had routine blood tests including RDW and PDW
      values. RESULTS: Saphenous vein grafts were found to be patent in 69 patients and
      occluded in 40 patients. Although RDW levels were similar between patients with
      patent and occluded grafts (13.1 +/- 1.1% and 13.2 +/- 0.7% respectively, p =
      0.37), PDW levels were significantly different between the two groups (13.1 +/-
      1.3% and 14.1 +/- 1.1 respectively, p = 0.03). Although time after CABG operation
      differs significantly between the two groups (p < 0.001), multiple logistic
      regression analyses showed that PDW levels were found to be significantly
      associated with the patency of vein graft (beta = 1.682, 95% CI 1.117-2.532, p =
      0.013). CONCLUSION: Our results showed that PDW levels were higher in patients
      with an occluded saphenous vein graft. However no association was found between
      the saphenous vein graft disease and RDW values. To verify this relationship
      between PDW values and saphenous vein graft patency, further investigations are
      needed.

PMID- 22955689
TI  - Elevated serum YKL-40 level predicts myocardial reperfusion and in-hospital MACE
      in patients with STEMI.
AB  - BACKGROUND: Macrophages in atherosclerotic plaques secrete YKL-40, a new
      biomarker of acute and chronic inflammation in patients with stable CAD. We
      hypothesized that YKL-40 may be a specific marker reflecting the burden of
      localized inflammation in myocardium and a predictor in patients with STEMI. In
      this study, we investigated the relationship of YKL-40 to in-hospital major
      adverse cardiac events (MACE), reperfusion parameters and its predictors in
      patients with STEMI. METHODS: In total, 80 patients with STEMI and no history of
      prior coronary artery disease (CAD), who underwent primary percutaneous coronary
      intervention (p-PCI), were enrolled consecutively. In addition, 30 patients with
      normal coronary arteries (NCA) were enrolled as a control group. Cardiac
      biomarker levels including creatinine kinase-MB fraction (CK-MB), troponin-I,
      admission glucose and inflammatory markers including leukocytes and YKL-40 levels
      were measured as admission values. RESULTS: In our study, YKL-40 levels
      correlated to high-sensitivity CRP levels (r = 0.333, p = 0.003), TIMI risk score
      (r = 0.445, p < 0.001), age (r = 0.477, p < 0.001), pain to balloon time (r =
      0.432, p < 0.001), leukocyte and neutrophil count (r = 0.386, p < 0.001 and r =
      0.430, p < 0.001, respectively), hemoglobin (r = - 0.345, p = 0.002), admission
      and fasting blood glucose (r = 0.388, p < 0.001 and r = 0.427, p < 0.001),
      creatinine levels (r = 0.395, p < 0.001) and myocardial blush grade (r = - 0.334,
      p = 0.004). When the patients were divided into two groups determined by presence
      or absence of MACE, the patients with MACE had significantly higher levels of YKL
      40 in comparison to the patients without MACE and the control group (194 +/- 104,
      114 +/- 61 and 110 +/- 53 MUg/L, p < 0.001, respectively). In multivariate
      logistic regression analysis in STEMI patients, only YKL-40 level (OR: 1.011,
      95%CI: 1.002-1.019, p = 0.011) and leukocyte count (OR: 1.264, 95%CI: 1.037
      1.540, p = 0.020) were the independent predictors for MACE. Sensitivity and
      specificity of YKL-40 to predict MACE, when 125 MUg/l was accepted as a cut-off
      value, were 84% and 70%, respectively. CONCLUSION: We found that serum YKL-40 is
      related to older age, increased admission glucose levels, leukocyte counts and
      decreased hemoglobin levels; YKL-40 level and leukocyte count independently
      predicted MACE.

PMID- 22955690
TI  - The acute effect of percutaneous mitral balloon valvuloplasty on atrial
      electromechanical delay and P-wave dispersion in patients with mitral stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The predisposition to atrial fibrillation (AF)
      in mitral stenosis (MS) has been demonstrated with several electrocardiographic
      (increased P-wave dispersion) and echocardiographic parameters (atrial
      electromechanical delay). Despite the improvement in P-wave dispersion after
      percutaneous mitral balloon valvuloplasty (PMBV), the changes in
      echocardiographic parameters related to AF risk are unknown. In this study we
      aimed to investigate the acute effect of PMBV on atrial electromechanical delay
      (EMD) assessed by tissue Doppler echocardiography in addition to
      electrocardiographic parameters. MATERIALS AND METHODS: This single-center study
      consisted of 30 patients with moderate or severe MS (23 females and seven males,
      aged 36.5 +/- 8.5 years, with a mean MVA of 1.1 +/- 0.2 cm) who underwent
      successful PMBV without complication at our clinic and 20 healthy volunteers from
      hospital staff as a control group (16 females and four males, aged 35.4 +/- 6
      years). We compared the two groups in regard to clinical, electrocardiographic
      and echocardiographic features. The patients with MS were also evaluated after
      PMBV within 72 h of the procedure. The P-wave dispersion was calculated from12
      lead ECG. Interatrial and intra-atrial EMDs were measured by tissue Doppler
      echocardiography. These ECG and echocardiographic parameters after PMBV were
      compared with previous values. RESULTS: The maximum P-wave duration (138 +/- 15
      vs. 101 +/- 6 ms, p < 0.01), PWD (58 +/- 18 vs 23 +/- 4, p < 0.01), the
      interatrial (55 +/- 16 vs 36 +/- 11 ms, p < 0.01) and left-sided intra-atrial EMD
      (40 +/- 11 vs 24 +/- 12 ms, p < 0.01) were higher in patients with MS than in
      healthy subjects. The left atrial (LA) diameter, LA volume and LA volume index
      had positive association with the interatrial (r = 0.5, p < 0.01; r = 0.5, p <
      0.01 and r = 0.5, p < 0.01, respectively) and left-sided intra-atrial EMD (r =
      0.5, p < 0.01; r = 0.4, p < 0.01; r = 0.4, p < 0.01 respectively). After PMBV,
      the interatrial (55 +/- 16 vs. 40 +/- 11 ms, p < 0.01) and left-sided intra
      atrial EMD (40 +/- 11 vs 31 +/- 10, p < 0.01) showed significant improvement
      compared to previous values. There was also a statistically significant
      difference in maximum P-wave duration and PWD between pre-and post-PMBV (138 +/-
      15 vs 130 +/- 14, p < 0.01, and 58 +/- 18 vs 49 +/- 16, p < 0.01, respectively).
      CONCLUSIONS: Our study shows that PMBV has a favorable effect on the
      electrocardiographic and echocardiographic parameters related with AF risk in
      patients with MS.

PMID- 22955691
TI  - Coronary rupture and pseudoaneurysm formation after extravascular migration of a
      paclitaxel eluting stent implanted in the left circumflex coronary artery.
AB  - As the implantation of drug eluting stents (DES) has become one of the most
      common clinical practices in interventional cardiology, the complications
      secondary to this procedure appear to have emerged increasingly over the past
      decade, with many cases of development of new coronary artery true aneurysms
      after DES implantation being reported. Here we present a case of coil
      embolization of a coronary pseudoaneurysm which presumably formed after
      extravascular migration of a DES.

PMID- 22955692
TI  - Preparation of dicationic palladium catalysts for asymmetric catalytic reactions.
AB  - The synthesis of Pd(OTf)(2).2H(2)O is described. This was used to generate two
      different types of chiral dicationic palladium complexes for highly
      enantioselective addition of aromatic amines to alpha, beta-unsaturated conjugate
      alkenes ([(R-BINAP)Pd(OH(2))(2)][OTf](2) and [(R-BINAP)Pd(MU-OH)](2)[OTf](2)).
      The resulting optically active N-arylated beta-amino acid derivatives are
      valuable synthetic intermediates for the synthesis of biologically active
      molecules and peptidomimetics. The reaction of (2E)-but-2-enoylcarbamate and
      aniline is shown as an example of the use of these catalysts for enantioselective
      aza-Michael addition. For the preparation of palladium(II) triflate, the time
      scale is 20 h 50 min, plus 5 h 15 min for the monomeric complex and plus 6 h 45
      min for the dimeric complex.

PMID- 22955693
TI  - Myelination of rodent hippocampal neurons in culture.
AB  - Axons of various hippocampal neurons are myelinated mainly postnatally, which is
      important for the proper function of neural circuits. Demyelination in the
      hippocampus has been observed in patients with multiple sclerosis, Alzheimer's
      disease or temporal lobe epilepsy. However, very little is known about the
      mechanisms and exact functions of the interaction between the myelin-making
      oligodendrocytes and the axons within the hippocampus. This is mainly
      attributable to the lack of a system suitable for molecular studies. We recently
      established a new myelin coculture from embryonic day (E) 18 rat embryos
      consisting of hippocampal neurons and oligodendrocytes, with which we identified
      a novel intra-axonal signaling pathway regulating the juxtaparanodal clustering
      of Kv1.2 channels. Here we describe the detailed protocol for this new coculture.
      It takes about 5 weeks to set up and use the system. This coculture is
      particularly useful for studying myelin-mediated regulation of ion channel
      trafficking and for understanding how neuronal excitability and synaptic
      transmission are regulated by myelination.

PMID- 22955694
TI  - Regioselective monodeprotection of peracetylated carbohydrates.
AB  - This protocol describes the regioselective deprotection of single hydroxyls in
      peracetylated monosaccharides and disaccharides by enzymatic or chemoenzymatic
      strategies. The introduction of a one-pot enzymatic step by using immobilized
      biocatalysts obviates the requirement to carry out tedious workups and time
      consuming purifications. By using this straightforward protocol, different per-O
      acetylated glycopyranosides (mono- or disaccharides, 1-substituted or glycals)
      can be transformed into a whole set of differentially monodeprotected 1-alcohols,
      3-alcohols, 4-alcohols and 6-alcohols in high yields. These tailor-made glycosyl
      acceptors can then be used for stereoselective glycosylation for oligosaccharide
      and glycoderivative synthesis. They have been successfully used as building
      blocks to synthesize tailor-made di- and trisaccharides involved in the structure
      of lacto-N-neo-tetraose and precursors of the tumor-associated carbohydrate
      antigen T and the antitumoral drug peracetylated beta-naphtyl-lactosamine. We are
      able to prepare a purified monoprotected carbohydrate in between 1 and 4 d. With
      this protocol, the small library of monodeprotected products can be synthesized
      in 1-2 weeks.

PMID- 22955695
TI  - Designing and using RNA scaffolds to assemble proteins in vivo.
AB  - RNA scaffolds are synthetic noncoding RNA molecules with engineered 3D folding
      harnessed to spatially organize proteins in vivo. Here we provide a protocol to
      design, express and characterize RNA scaffolds and their cognate proteins within
      1 month. The RNA scaffold designs described here are based on either monomeric or
      multimeric units harboring RNA aptamers as protein docking sites. The scaffolds
      and proteins are cloned into inducible plasmids and expressed to form functional
      assemblies. RNA scaffolds find applications in many fields in which in vivo
      organization of biomolecules is of interest. RNA scaffolds provide extended
      flexibility compared with DNA or protein scaffolding strategies through
      programmed modulation of multiple protein stoichiometry and numbers, as well as
      the proteins' relative distances and spatial orientations. For synthetic biology,
      RNA scaffolds provide a new platform that can be used to increase yields of
      sequential metabolic pathways.

PMID- 22955696
TI  - Adjusting Medicaid managed care payments for changes in health status.
AB  - Risk adjustment of managed care organization (MCO) payments is essential to avoid
      creating financial incentives for MCOs adopting enrollee selection strategies.
      However, all risk-adjustment methods have an inherent structural flaw that
      rewards preventable deterioration in enrollee health status and improved coding
      of disease burden. We propose a payment adjustment to offset this flaw. We use a
      database of 1,237,528 continuously enrolled beneficiaries to quantify the payment
      impact of change in enrollee health status over time for enrollees with two
      common chronic illnesses, hypertension and diabetes. The payment impact caused by
      the change in enrollee health status across MCOs ranged from +3.67% to -7.27% for
      enrollees with diabetes and from +5.25% to -7.69% for enrollees with
      hypertension. The MCO payment impact for diabetes and hypertension ranged from
      +0.19% to -0.31%. This difference can be used as the basis for creating payment
      incentives for MCOs to reduce the long-term costs of chronically ill enrollees.

PMID- 22955697
TI  - Organizational transformation: a systematic review of empirical research in
      health care and other industries.
AB  - Health care organization leaders and policy makers seeking ways to reform the
      delivery of health care have become increasingly interested in transformational
      change. To foster understanding of how organizational transformation occurs and
      to stimulate further research, we report findings from a systematic review of
      empirical research on transformational change in the health care and non-health
      care literature, with a focus on the antecedents, processes (or paths), and
      outcomes of transformational change. Fifty-six studies, of which 13 were in
      health care, met our selection criteria. With one exception, all were published
      since 1990, indicating the recent upsurge of interest in this area. Limited
      differences were found between health care and non-health care studies. Available
      research documents the multiplicity of factors affecting change and the
      complexity of their interactions, but less information is available about the
      processes of transformational change than about its antecedents and consequences.
      Research and practice implications are discussed.

PMID- 22955698
TI  - Accuracy of do not resuscitate (DNR) in administrative data.
AB  - This article evaluates the accuracy of reporting do not resuscitate (DNR) orders
      in administrative data for use in risk-adjusted hospital assessments. We compared
      DNR reporting by 48 California hospitals in 2005 patient discharge data (PDD)
      with gold-standard assessments made by registered nurses (RNs) who reabstracted
      1,673 records of patients with myocardial infarction, pneumonia, or heart
      failure. The PDD agreed with the RN reabstraction in 1,411 (84.3%) cases. The
      administrative data did not reflect a DNR order in 71 of 512 records where the RN
      indicated there was (14% false negative rates), and reflected a DNR order in 191
      of 1,161 records where the RN indicated there was not (16% false positive rate).
      The accuracy of DNR was more problematic for patients who died, suggesting that
      hospital-reported DNR is problematic for capturing patient preferences for
      resuscitation that can be used for risk-adjusted outcomes assessments.

PMID- 22955699
TI  - The right tool is what they need, not what we have: a taxonomy of appropriate
      levels of precision in patient risk communication.
AB  - While patients often receive risk information, exactly what constitutes being
      "informed" about health risks is often unclear. Patients have specific needs,
      such as avoiding being surprised by a possible outcome and making complex risk
      trade-off decisions. Yet all risk information is not equally informative for
      those needs. In this article, I present a taxonomy of seven risk concepts that
      vary in their inherent precision and evaluability. Congruent with the "less is
      more" concept, I argue that risk communications should use formats that are
      tailored to message recipients' specific informational needs. Simpler formats can
      be used when patients only need to order risks, while more complex numerical
      probability statements will be necessary when patients need to assess differences
      in risk magnitude and put those differences into meaningful context. Selecting
      need-congruent formats when designing communications about risks to patients is a
      novel approach that may better support patients' health care decision making.

PMID- 22955700
TI  - Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility
      to ulcerative colitis.
AB  - Interleukin-17A plays a role in tissue inflammation by inducing release of
      proinflammatory and neutrophil-mobilizing cytokines. We investigated the
      association between ulcerative colitis (UC) and polymorphisms of IL17A, rs2275913
      (-197 G > A), and rs3748067 (*1249 C > T). The study was performed in 475 healthy
      subjects (controls) and 202 with UC (UC cases), including 113 controls and 64 UC
      cases from previous study. We employed the multiplex PCR-SSCP method to detect
      gene polymorphisms. The minor allele frequency of rs2275913 was significantly
      higher but that of rs3748067 was significantly lower in UC cases than controls.
      The rs2275913 minor homozygote (AA) had an increased risk of the development of
      UC, whereas rs3748067 minor carrier (CT + TT) had decreased risks for the
      development of UC. When compared with LR group (rs2275913 GG + GA with rs3748067
      CT + TT), HR group (rs2275913 AA with rs3748067 CC) had a more increased risk of
      the development of UC (OR, 3.38; p = 0.0007). The polymorphisms of IL17A were
      associated with the noncontinuous and pancolitis phenotypes of UC. Our results
      suggest that IL17A polymorphisms (both rs2275913 and rs3748067) influence the
      susceptibility to and pathophysiological features of UC, coordinately. 

PMID- 22955702
TI  - Identifying the demographic processes relevant for species conservation in human
      impacted areas: does the model matter?
AB  - The identification of the demographic processes responsible for the decline in
      population growth rate (lambda) in disturbed areas would allow conservation
      efforts to be efficiently directed. Integral projection models (IPMs) are used
      for this purpose, but it is unclear whether the conclusions drawn from their
      analysis are sensitive to how functional structures (the functions that describe
      how survival, growth and fecundity vary with individual size) are selected. We
      constructed 12 IPMs that differed in their functional structure by combining two
      reproduction models and three functional expressions (generalized linear, cubic
      and additive models), each with and without simplification. Models were
      parameterized with data from two populations of two endangered cacti subject to
      different disturbance intensities. For each model, we identified the demographic
      processes that most affected lambda in the presence of disturbance. Simulations
      were performed on artificial data and analyzed as above to assess the generality
      of the results. In both empirical and simulated data, the same processes were
      identified as making the largest contribution to changes in lambda regardless of
      the functional structure. The major differences in the results were due to
      misspecification of the fecundity functions, whilst functional expression and
      model simplification had lesser effects. Therefore, as long as the demographic
      attributes of the species are well known and incorporated into the model, IPMs
      will robustly identify the processes that most affect the growth of populations
      subject to disturbance, making them a reliable tool for developing conservation
      strategies.

PMID- 22955701
TI  - The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces
      apoptosis in human cholangiocarcinoma cells.
AB  - The aim of this study was to investigate the effects of 17-Allylamino-17
      demethoxygeldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, on the
      proliferation, cell cycle, and apoptosis of human cholangiocarcinoma (CCA) cells.
      Cell proliferation and cell cycle distribution were measured by the MTT assay and
      flow cytometry analysis, respectively. Induction of apoptosis was determined by
      flow cytometry and Hoechst staining. The expressions of cleaved poly ADP-ribose
      polymerase (PARP), Bcl-2, Survivin, and Cyclin B1 were detected by Western blot
      analysis. The activity of caspase-3 was also examined. We found that 17-AAG
      inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA
      cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the
      up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also
      observed in CCA cells treated with 17-AAG. In conclusion, our data suggest that
      the inhibition of HSP90 function by 17-AAG may provide a promising therapeutic
      strategy for the treatment of human CCA. 

PMID- 22955703
TI  - Long-term memory of hierarchical relationships in free-living greylag geese.
AB  - Animals may memorise spatial and social information for many months and even
      years. Here, we investigated long-term memory of hierarchically ordered
      relationships, where the position of a reward depended on the relationship of a
      stimulus relative to other stimuli in the hierarchy. Seventeen greylag geese
      (Anser anser) had been trained on discriminations between successive pairs of
      five or seven implicitly ordered colours, where the higher ranking colour in each
      pair was rewarded. Geese were re-tested on the task 2, 6 and 12 months after
      learning the dyadic colour relationships. They chose the correct colour above
      chance at all three points in time, whereby performance was better in colour
      pairs at the beginning or end of the colour series. Nonetheless, they also
      performed above chance on internal colour pairs, which is indicative of long-term
      memory for quantitative differences in associative strength and/or for relational
      information. There were no indications for a decline in performance over time,
      indicating that geese may remember dyadic relationships for at least 6 months and
      probably well over 1 year. Furthermore, performance in the memory task was
      unrelated to the individuals' sex and their performance while initially learning
      the dyadic colour relationships. We discuss possible functions of this long-term
      memory in the social domain.

PMID- 22955704
TI  - Olive baboons communicate intentionally by pointing.
AB  - A pointing gesture creates a referential triangle that incorporates distant
      objects into the relationship between the signaller and the gesture's recipient.
      Pointing was long assumed to be specific to our species. However, recent reports
      have shown that pointing emerges spontaneously in captive chimpanzees and can be
      learned by monkeys. Studies have demonstrated that both human children and great
      apes use manual gestures (e.g. pointing), and visual and vocal signals, to
      communicate intentionally about out-of-reach objects. Our study looked at how
      monkeys understand and use their learned pointing behaviour, asking whether it is
      a conditioned, reinforcement-dependent response or whether monkeys understand it
      to be a mechanism for manipulating the attention of a partner (e.g. a human). We
      tested nine baboons that had been trained to exhibit pointing, using operant
      conditioning. More specifically, we investigated their ability to communicate
      intentionally about the location of an unreachable food reward in three contexts
      that differed according to the human partner's attentional state. In each
      context, we quantified the frequency of communicative behaviour (auditory and
      visual signals), including gestures and gaze alternations between the distal food
      and the human partner. We found that the baboons were able to modulate their
      manual and visual communicative signals as a function of the experimenter's
      attentional state. These findings indicate that monkeys can intentionally produce
      pointing gestures and understand that a human recipient must be looking at the
      pointing gesture for them to perform their attention-directing actions. The
      referential and intentional nature of baboons' communicative signalling is
      discussed.

PMID- 22955705
TI  - Directional paths ... The next steps.

PMID- 22955707
TI  - Team composition and perceived roles of team members in the trauma bay.
AB  - Perceptions of trauma team members and their roles may impact team performance,
      requiring intervention. Participant observation and semistructured interviews
      were performed with trauma team members: attendings, nurses, fellows, residents,
      and medical students. Some team members do not include nurses as members of the
      team. A greater proportion of male than female team leaders perceived their role
      as teacher or educator. Nurses, attendings, and fellows, provided parallel
      descriptions of good leaders, whereas medical students and residents stressed
      other qualities. Inconsistencies in trauma team role definition and membership
      should be addressed, toward the goal of improving team communication and patient
      outcomes.

PMID- 22955708
TI  - Predictors of pneumonia in trauma patients with pulmonary contusion.
AB  - The purpose of this article was to determine assessable risk levels for pneumonia
      in trauma patients with pulmonary contusion. A retrospective review and analysis
      of national trauma data of patients with pulmonary contusion were identified to
      develop a risk assessment model. Trauma data for 2007 were used to determine risk
      factors for subsequent complication of pneumonia in pulmonary contusion patients.
      Available patient comorbidities were considered in model development. Next, 2008
      data were used to test and finalize model. Pneumonia risk was categorized into 3
      ordinal levels, based on equal-sized proportions of pulmonary contusion patients.
      Significant risk factors for pneumonia included age, gender, pulse rate, systolic
      blood pressure, obesity, Glasgow Coma Scale motor score, and ventilation on
      admission. The final risk adjustment model had good fit and discrimination. Study
      analyses used more than 40 000 trauma patient data to devise assessable risk
      levels for pneumonia in pulmonary contusion diagnosed patients. Study data can
      assist in direction of care and triaging of urgent care patients at risk of
      pneumonia, possibly leading to mitigation and prevention of pneumonia in at risk
      patients. Further review of study outcomes should occur to fully understand
      applicability and usefulness in urgent settings.

PMID- 22955709
TI  - Screening, brief intervention, and referral to treatment in the adolescent trauma
      population: examining barriers to implementation.
AB  - Adolescence is a critical stage in human development in which individuals gain
      independence from parents. This vulnerable period of life often involves
      experimentation with intoxicating substances and other risky behaviors. This
      combination of factors may lead to traumatic injury that requires emergency
      department treatment and hospitalization. This scenario presents an opportunity
      for screening, education and treatment regarding substance abuse. Policies that
      support such measures have been shown to be poorly followed. The aim of this
      manuscript is to identify and discuss some of the barriers to implementation of
      an alcohol and drug screening policy for adolescent trauma patients admitted for
      inpatient hospital care.

PMID- 22955711
TI  - Chronic pain at 4 months in hospitalized trauma patients: incidence and life
      interference.
AB  - Many studies report on the incidence of chronic pain. However, deficiencies exist
      in prior research making it difficult to generalize results to trauma patients.
      This study evaluated the incidence of chronic pain in trauma patients at 4 months
      posttrauma and effect chronic pain has on life interference. The incidence of
      chronic pain was present in 79.2% of trauma patients 4 months posttrauma and a
      strong positive correlation (n = 80, r = 0.79, P < 0.001) existed between chronic
      pain severity and the effect on life interference. Chronic pain is prevalent and
      causes significant life interference in traumatically injured patients.

PMID- 22955712
TI  - Diagnosing increased intracranial pressure.
AB  - Increased intracranial pressure (ICP) is a challenging complication to treat
      within a critical care setting. It is imperative that clinicians use a stepwise
      approach in developing a diagnosis, as to be comprehensive and decrease morbidity
      and mortality related to increased ICP. This article provides an algorithm that
      can be used as a clinical guideline when assessing a patient who has an ICP
      monitor in place and is presenting with increased ICP. The algorithm is inclusive
      and composed of a history of present illness, review of systems, physical
      assessment, labs, and further testing.

PMID- 22955713
TI  - Hospitalized injured older adults: clinical utility of a rib fracture scoring
      system.
AB  - INTRODUCTION: A rib fracture scoring system (RFS) was proposed for risk
      assessment in hospitalized injured older adults. Development was limited to one
      site. PURPOSE: To validate the RFS for clinical utility in predicting outcomes in
      another hospital setting. METHODS: Retrospective cohort design. SAMPLE: Patients
      aged 50 years or older with rib fracture(s) (N = 81). SETTING: Level II trauma
      center. DATA COLLECTION: Trauma registry data (2002-2005). DATA ANALYSIS:
      Bivariate correlations, linear and logistic regression models.
      RESULTS/CONCLUSIONS: While the RFS is associated with outcomes, explanatory value
      is low. Further research is needed to identify hospitalized injured older adults
      most likely to utilize health services.

PMID- 22955715
TI  - Trauma pain protocol: an interdisciplinary approach to process improvement.
AB  - The trauma pain protocol was developed in response to nursing staff concerns
      regarding pain management practices and hospital-wide goals. Data collected on
      pain management practices within the trauma patient population identified
      inconsistencies with the transition of patient-controlled analgesia (PCA) to oral
      (PO) and intravenous (IV) pain medications. Nursing staff cited concerns with the
      frequent need for calls to clinicians to obtain additional pain medication orders
      following discontinuation of PCA. An interdisciplinary team developed a protocol
      to address appropriate PCA to PO/IV conversion, adjuvant medications, opioid
      reversal, and management of adverse effects. Data collected from a 4-month pilot
      of the protocol demonstrated a reduction in changes made to PO/IV medications
      following discontinuation of PCA. Nursing response to the protocol included
      increased satisfaction with pain management practices and a perception of time
      saved through reduced need for calls to clinicians for additional pain medication
      modifications. We conclude that this protocol results in a more individualized,
      evidence-based transition from PCA to PO/IV.

PMID- 22955716
TI  - Identifying the association among risk factors and mortality in trauma patients
      with intra-abdominal hypertension and abdominal compartment syndrome.
AB  - Intra-abdominal hypertension and abdominal compartment syndrome (ACS) have become
      key players in increasing mortality among critically ill trauma patients. Many
      risk factors place the trauma patient at risk for developing ACS. Very few
      studies exist to establish a predictive relationship between any one risk factor
      and mortality among these patients. A retrospective, nonexperimental, descriptive
      project considering preidentified risk factors and their direct association with
      mortality in patients exhibiting intra-abdominal hypertension and ACS was carried
      out in an urban level 1 trauma center. Polytransfusion was strongly predicted
      among those with ACS for mortality (P < .001). Mortality was strongly associated
      with a reported history of diabetes (P < .05). The total amount of blood products
      showed a perfect correlation with death as well (r = 1.0, P < .001).

PMID- 22955717
TI  - Challenges in conducting research after family presence during resuscitation.
AB  - Family presence during resuscitation (FPDR) is an option occurring in clinical
      practice. National clinical guidelines on providing the option of FPDR are
      available from the American Association of Critical-Care Nurses, American Heart
      Association, Emergency Nurses Association, and Society of Critical Care Medicine.
      The FPDR option currently remains controversial, underutilized, and not the usual
      practice with trauma patients. This article is based on the methodological and
      practical research challenges associated with an ongoing study to examine the
      effects of the FPDR option on family outcomes in patients experiencing critical
      injury after motor vehicle crashes and gunshot wounds. The primary aim of this
      study was to examine the effects of the FPDR option on family outcomes of
      anxiety, stress, well-being, and satisfaction and compare those outcomes in
      families who participate in FPDR to those families who do not participate in
      FPDR. Examples of real clinical challenges faced by the researchers are described
      throughout this article. Research challenges include design, sampling,
      inclusion/exclusion criteria, human subjects, and procedures. Recruitment of
      family members who participated in the FPDR option is a complex process,
      especially after admission to the critical care unit.

PMID- 22955718
TI  - Outer retinal tubulations in chronic central serous chorioretinopathy.

PMID- 22955719
TI  - [Basic principles of therapy with neuropsychotropic drugs].
AB  - This review provides the general principles for a rational therapy with
      psychotropic drugs. It covers the discussion on the basics of the
      pharmacokinetics (with consideration of drug metabolism and the importance of
      genetic polymorphisms), pharmacodynamics (drug-receptor interaction, receptor
      pharmacology) and the effects of chronic administration of neuropsychotropic
      drugs on behavior. The reader will thus obtain the basis and stimulation for
      further study.

PMID- 22955722
TI  - Australian population cohort study of newly arrived refugee children:  how
      effective is predeparture measles and rubella vaccination?
AB  - BACKGROUND: Predeparture medical screening and measles-mumps-rubella vaccination
      are routinely given to refugee children before departure from most transit
      countries en route to Australia. OBJECTIVES: The purpose of this study was to
      evaluate the effectiveness of this single measles-mumps-rubella vaccine and the
      reliability of its documentation. This is important in determining refugees'
      susceptibility to measles and rubella and the risk to the nonvaccinated
      community. METHODS: We analyzed measles and rubella serology in a comprehensively
      screened population of newly arrived refugees. We reviewed seropositivity rates
      based on age, sex, country of departure and vaccine documentation. RESULTS: Of
      164 children screened, 139 (84.8%) were immune to rubella; 143 (87.7%) to measles
      and 119 (73.0%) to both. There was no significant difference in immunity among
      those of different ages or those departing different continents. Immunity rates
      among those with documented measles-mumps-rubella tended to be higher: 91.1% for
      rubella, 89.1% for measles and 80.0% for both diseases, but this did not reach
      significance at the 5% level. There was a significant difference between males
      (65.9%) and females (81.3%) immune to both diseases (P = 0.042). CONCLUSIONS:
      This cohort demonstrated similar measles and rubella seropositivity rates to
      those of the Australian population, but lower rates than population
      seroconversion studies, which have been estimated at 95%. Males were less likely
      to be immune. Rates in those with documented vaccination approximated
      seroconversion studies. This confirms the appropriateness of current guidelines
      which suggest that immunization is not required in the face of documented prior
      vaccination, but is required without such documentation.

PMID- 22955723
TI  - Rational design of oriented assembly of gold nanospheres with nanorods by biotin
      streptavidin connectors.
AB  - Through the different functionalities on Au nanosphere (AuNSs) and Au nanorod
      (AuNRs) surfaces, we successfully control AuNSs attachment onto either the end or
      side surface of anisotropic AuNRs via bio-recognition, and then consciously
      construct side-by-side or end-to-end assembly nanostructures. This study provides
      a feasible approach to organize nanoparticles with different morphologies into
      controllable assembly geometries, which can potentially benefit the construction
      of future nanodevices.

PMID- 22955724
TI  - Home point-of-care international normalised ratio monitoring sustained by a non
      selective educational program in children.
AB  - Adverse events related to vitamin K antagonist (VKA) therapy might be reduced by
      point-of-care international normalised ratio (POC INR) monitoring supported by an
      education program (EP). Our aim was to evaluate the efficacy of a non-selective
      VKA paediatric EP (regardless of the social, economic, educational or linguistic
      levels) by analysing the time spent in the therapeutic range (TTR), VKA adverse
      events and compliance to treatment, and INR control prescriptions. The EP was
      modified from the pediatric EP previously described but improved by a
      specifically devised child-focused game. One hundred four consecutive children
      (median age 8 years) receiving VKA were included in a standardised EP. Patients
      were in self-testing, and dose adjustments were made by a single physician for
      three tolerance ranges according to the underlying disease: [2.5-4], [1.8-3.2],
      and [1.5-2.5]. The median follow-up was 481 days [70-1,001]. The overall TTR was
      81.4% [36-100]. The TTR were 74%, 85.6% and 89% for the ranges [2.5-4], [1.8
      3.2], and [1.5-2.5], respectively. These results were sustainable during the
      study period. Only one serious VKA adverse event was recorded. The median number
      of POC INR tests was 2.5 [1.6-5.7] INR per patient and month. Patients/families
      performed POC INR when requested in 86.9% of the cases. More than 90% of the
      families found the EP supportive and wished to follow a long-term reinforcement
      program. In conclusion, this non-selective child-focused EP for VKA therapy,
      strongly supported by our dedicated game, is useful in maintaining efficacy,
      safety and compliance to anticoagulation and its monitoring.

PMID- 22955725
TI  - Occurrence of organotins in the Yangtze River and the Jialing River in the urban
      section of Chongqing, China.
AB  - The occurrence of organotins in the Yangtze River and the Jialing River in the
      urban section of Chongqing, China and their impact on drinking water waterworks
      are reported in this study. Water samples were extracted by solid-phase
      microextraction and measured using a gas chromatograph with mass spectrometer.
      The results showed that the rivers studied were polluted by both butyltins and
      phenyltins and that the butyltin species was the dominant pollutant. Butyltins,
      especially monobutyltin, were detected in all 18 sampling stations, and
      phenyltins were detected only in 11 sampling stations. Majority of the organotins
      were MBTs with concentrations varying from 27.3 to 1,145.8 ng Sn L(-1).
      Diphenyltin and dibutyltin were the second most common with the highest levels of
      113.7 and 202.5 ng Sn L(-1), respectively. Monophenyltin, tributyltin, and
      triphenyltin had the lowest detection rates with concentration levels of 9.7,
      161.8, and 37.2 ng Sn L(-1), respectively. Some of the organotins were also
      detected in drinking water waterworks, which posed a threat to the water quality
      of Chongqing.

PMID- 22955726
TI  - BBB on chip: microfluidic platform to mechanically and biochemically modulate
      blood-brain barrier function.
AB  - The blood-brain barrier (BBB) is a unique feature of the human body, preserving
      brain homeostasis and preventing toxic substances to enter the brain. However, in
      various neurodegenerative diseases, the function of the BBB is disturbed.
      Mechanisms of the breakdown of the BBB are incompletely understood and therefore
      a realistic model of the BBB is essential. We present here the smallest model of
      the BBB yet, using a microfluidic chip, and the immortalized human brain
      endothelial cell line hCMEC/D3. Barrier function is modulated both mechanically,
      by exposure to fluid shear stress, and biochemically, by stimulation with tumor
      necrosis factor alpha (TNF-alpha), in one single device. The device has
      integrated electrodes to analyze barrier tightness by measuring the
      transendothelial electrical resistance (TEER). We demonstrate that hCMEC/D3 cells
      could be cultured in the microfluidic device up to 7 days, and that these
      cultures showed comparable TEER values with the well-established Transwell assay,
      with an average (+/- SEM) of 36.9 Omega.cm(2) (+/- 0.9 Omega.cm(2)) and 28.2
      Omega.cm(2) (+/- 1.3 Omega.cm(2)) respectively. Moreover, hCMEC/D3 cells on chip
      expressed the tight junction protein Zonula Occludens-1 (ZO-1) at day 4.
      Furthermore, shear stress positively influenced barrier tightness and increased
      TEER values with a factor 3, up to 120 Omega.cm(2). Subsequent addition of TNF
      alpha decreased the TEER with a factor of 10, down to 12 Omega.cm(2). This
      realistic microfluidic platform of the BBB is very well suited to study barrier
      function in detail and evaluate drug passage to finally gain more insight into
      the treatment of neurodegenerative diseases.

PMID- 22955727
TI  - An ATP sensitive light addressable biosensor for extracellular monitoring of
      single taste receptor cell.
AB  - Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste
      buds for taste signal transmission and processing. Measurements of ATP secreted
      from single taste receptor cell (TRC) with high sensitivity and specificity are
      essential for investigating mechanisms underlying taste cell-to-cell
      communications. In this study, we presented an aptamer-based biosensor for the
      detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was
      used as recognition element and its DNA competitor was served as signal
      transduction element that was covalently immobilized on the surface of light
      addressable potentiometric sensor (LAPS). Due to the light addressable capability
      of LAPS, local ATP secretion from single TRC can be detected by monitoring the
      working potential shifts of LAPS. The results show this biosensor can detect ATP
      with high sensitivity and specificity. It is demonstrated this biosensor can
      effectively detect the local ATP secretion from single TRC responding to tastant
      mixture. This biosensor could provide a promising new tool for the research of
      taste cell-to-cell communications as well as for the detection of local ATP
      secretion from other types of ATP secreting individual cells.

PMID- 22955728
TI  - Dealcoholized red wine decreases systolic and diastolic blood pressure and
      increases plasma nitric oxide: short communication.
AB  - RATIONALE: Experimental studies have shown a potential blood pressure (BP)
      lowering effect of red wine polyphenols, whereas the effects of ethanol and
      polyphenols on BP in humans are not yet clear. OBJECTIVE: The aim of the present
      work was to evaluate the effects of red wine fractions (alcoholic and
      nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high
      cardiovascular risk. METHODS AND RESULTS: Sixty-seven men at high cardiovascular
      risk were studied. After a 2-week run-in period, subjects were randomized into 3
      treatment periods in a crossover clinical trial, with a common background diet
      plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine,
      or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and
      after each intervention, anthropometrical parameters, BP and plasma NO were
      measured. Systolic and diastolic BP decreased significantly after the
      dealcoholized red wine intervention and these changes correlated with increases
      in plasma NO. CONCLUSIONS: Dealcoholized red wine decreases systolic and
      diastolic BP. Our results point out through an NO-mediated mechanism. The daily
      consumption of dealcoholized red wine could be useful for the prevention of low
      to moderate hypertension. Trial registered at controlled-trials.com:
      ISRCTN88720134.

PMID- 22955729
TI  - Red wine and cardiovascular health.

PMID- 22955731
TI  - Asymmetric fate of the posterior part of the second heart field results in
      unexpected left/right contributions to both poles of the heart.
AB  - RATIONALE: The second heart field (SHF) contains progenitors of all heart
      chambers, excluding the left ventricle. The SHF is patterned, and the anterior
      region is known to be destined to form the outflow tract and right ventricle.
      OBJECTIVE: The aim of this study was to map the fate of the posterior SHF (pSHF).
      METHODS AND RESULTS: We examined the contribution of pSHF cells, labeled by
      lipophilic dye at the 4- to 6-somite stage, to regions of the heart at 20 to 25
      somites, using mouse embryo culture. Cells more cranial in the pSHF contribute to
      the atrioventricular canal (AVC) and atria, whereas those more caudal generate
      the sinus venosus, but there is intermixing of fate throughout the pSHF. Caudal
      pSHF contributes symmetrically to the sinus venosus, but the fate of cranial pSHF
      is left/right asymmetrical. Left pSHF moves to dorsal left atrium and superior
      AVC, whereas right pSHF contributes to right atrium, ventral left atrium, and
      inferior AVC. Retrospective clonal analysis shows the relationships between AVC
      and atria to be clonal and that right and left progenitors diverge before first
      and second heart lineage separation. Cranial pSHF cells also contribute to the
      outflow tract: proximal and distal at 4 somites, and distal only at 6 somites.
      All outflow tract-destined cells are intermingled with those that will contribute
      to inflow and AVC. CONCLUSIONS: These observations show asymmetric fate of the
      pSHF, resulting in unexpected left/right contributions to both poles of the heart
      and can be integrated into a model of the morphogenetic movement of cells during
      cardiac looping.

PMID- 22955730
TI  - Myeloid cell-specific ABCA1 deletion protects mice from bacterial infection.
AB  - RATIONALE: ATP-binding cassette transporter A1 (ABCA1) plays a critical role in
      eliminating excess free cholesterol from tissues by effluxing cellular free
      cholesterol and phospholipids to lipid-poor apolipoprotein AI. Macrophage ABCA1
      also dampens proinflammatory myeloid differentiation primary-response protein 88
      dependent toll-like receptor signaling by reducing cellular membrane free
      cholesterol and lipid raft content, indicating a role of ABCA1 in innate
      immunity. However, whether ABCA1 expression has a role in regulating macrophage
      function in vivo is unknown. OBJECTIVE: We investigated whether macrophage ABCA1
      expression impacts host defense function, including microbial killing and
      chemotaxis. METHODS AND RESULTS: Myeloid cell-specific ABCA1 knockout (MSKO) vs
      wild-type mice were infected with Listeria monocytogenes (Lm) for 36 hours or 72
      hours before euthanasia. Lm-induced monocytosis was similar for wild-type and
      MSKO mice; however, MSKO mice were more resistant to Lm infection, with
      significantly less body weight loss, less Lm burden in liver and spleen, and less
      hepatic damage 3 days postinfection. In addition, Lm-infected MSKO mouse livers
      had: (1) greater monocyte chemoattractant protein-1 and macrophage inflammatory
      protein-2 expression; (2) more monocyte/macrophage infiltration; (3) less neutral
      lipid accumulation; and (4) diminished expression of lipogenic genes. MSKO
      macrophages showed enhanced chemotaxis toward chemokines in vitro and increased
      migration from peritoneum in response to lipopolysaccharide in vivo. Lm infection
      of wild-type macrophages markedly reduced expression of ABCA1 protein, as well as
      other cholesterol export proteins (such as ATP-binding cassette transporter G1
      and apolipoprotein E). CONCLUSIONS: Myeloid-specific ABCA1 deletion favors host
      response to and clearance of Lm. Macrophage Lm infection reduces expression of
      cholesterol export proteins, suggesting that diminished cholesterol efflux
      enhances innate immune function of macrophages.

PMID- 22955732
TI  - CLP36 is a negative regulator of glycoprotein VI signaling in platelets.
AB  - RATIONALE: At sites of vascular injury, exposed subendothelial collagens not only
      trigger sudden platelet adhesion and aggregation, thereby initiating normal
      hemostasis, but also can lead to acute ischemic diseases, such as myocardial
      infarction or stroke. The glycoprotein (GP) VI/Fc receptor gamma-chain complex is
      a central regulator of these processes because it mediates platelet activation on
      collagens through a series of tyrosine phosphorylation events downstream of the
      Fc receptor gamma-chain-associated immunoreceptor tyrosine-based activation
      motif. GPVI signaling has to be tightly regulated to prevent uncontrolled
      intravascular platelet activation, but the underlying mechanisms are not fully
      understood. OBJECTIVE: We studied the role of PDZ and LIM domain family member
      CLP36 in platelet physiology in vitro and in vivo. METHODS AND RESULTS: We report
      that CLP36 acts as a major inhibitor of GPVI immunoreceptor tyrosine-based
      activation motif signaling in platelets. Platelets from mice either expressing a
      low amount of a truncated form of CLP36 lacking the LIM domain (Clp36(DeltaLIM))
      or lacking the whole protein (Clp36(-/-)) displayed profound hyperactivation in
      response to GPVI agonists, whereas other signaling pathways were unaffected. This
      was associated with hyperphosphorylation of signaling proteins and enhanced
      Ca(2+) mobilization, granule secretion, and integrin activation downstream of
      GPVI. The lack of functional CLP36 translated into accelerated thrombus formation
      and enhanced procoagulant activity, assembling a prothrombotic phenotype in vivo.
      CONCLUSIONS: These data reveal an inhibitory function of CLP36 in GPVI
      immunoreceptor tyrosine-based activation motif signaling and establish it as a
      key regulator of arterial thrombosis.

PMID- 22955734
TI  - The role of protein hydrophobicity in thionin-phospholipid interactions: a
      comparison of alpha1 and alpha2-purothionin adsorbed anionic phospholipid
      monolayers.
AB  - The plant defence proteins alpha1- and alpha2-purothionin (Pth) are type 1
      thionins from common wheat (Triticum aestivum). These highly homologous proteins
      possess characteristics common amongst antimicrobial peptides and proteins, that
      is, cationic charge, amphiphilicity and hydrophobicity. Both alpha1- and alpha2
      Pth possess the same net charge, but differ in relative hydrophobicity as
      determined by C18 reversed phase HPLC. Brewster angle microscopy, X-ray and
      neutron reflectometry, external reflection FTIR and associated surface pressure
      measurements demonstrated that alpha1 and alpha2-Pth interact strongly with
      condensed phase 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG)
      monolayers at the air/liquid interface. Both thionins disrupted the in-plane
      structure of the anionic phospholipid monolayers, removing lipid during this
      process and both penetrated the lipid monolayer in addition to adsorbing as a
      single protein layer to the lipid head-group. However, analysis of the
      interfacial structures revealed that the alpha2-Pth showed faster disruption of
      the lipid film and removed more phospholipid (12%) from the interface than alpha1
      Pth. Correlating the protein properties and lipid binding activity suggests that
      hydrophobicity plays a key role in the membrane lipid removal activity of
      thionins.

PMID- 22955733
TI  - MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial
      cells by promoting vascular endothelial growth factor signaling.
AB  - RATIONALE: Formation and remodeling of the vasculature during development and
      disease involve a highly conserved and precisely regulated network of attractants
      and repellants. Various signaling pathways control the behavior of endothelial
      cells, but their posttranscriptional dose titration by microRNAs is poorly
      understood. OBJECTIVE: To identify microRNAs that regulate angiogenesis. METHODS
      AND RESULTS: We show that the highly conserved microRNA family encoding miR-10
      regulates the behavior of endothelial cells during angiogenesis by positively
      titrating proangiogenic signaling. Knockdown of miR-10 led to premature
      truncation of intersegmental vessel growth in the trunk of zebrafish larvae,
      whereas overexpression of miR-10 promoted angiogenic behavior in zebrafish and
      cultured human umbilical venous endothelial cells. We found that miR-10
      functions, in part, by directly regulating the level of fms-related tyrosine
      kinase 1 (FLT1), a cell-surface protein that sequesters vascular endothelial
      growth factor, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1
      protein levels upon miR-10 knockdown in zebrafish and in human umbilical venous
      endothelial cells inhibited the angiogenic behavior of endothelial cells largely
      by antagonizing vascular endothelial growth factor receptor 2 signaling.
      CONCLUSIONS: Our study provides insights into how FLT1 and vascular endothelial
      growth factor receptor 2 signaling is titrated in a microRNA-mediated manner and
      establishes miR-10 as a potential new target for the selective modulation of
      angiogenesis.

PMID- 22955735
TI  - Then and now.

PMID- 22955736
TI  - Malteser compromise.

PMID- 22955737
TI  - Inadequate knowledge.

PMID- 22955738
TI  - Astonishing dentitions.

PMID- 22955739
TI  - A suitable method.

PMID- 22955740
TI  - Peritendinitis crepitans.

PMID- 22955742
TI  - The real dilemma.

PMID- 22955741
TI  - Lozenge risks.

PMID- 22955744
TI  - Titanium fragments found in tissue near implants.

PMID- 22955756
TI  - Sugar-free medicines are counterproductive.
AB  - Sugar in food and drinks is responsible for the poor dental health of many
      children and adults. On the other hand, there is no evidence that the small
      amount of sugar in medicines has been responsible for any dental problems. A
      recent British Heart Foundation survey found that nearly one in three UK children
      are eating sweets, chocolate and crisps three or more times a day. Hence it is
      futile administering sugar-free medicine to a child consuming lot of sweets.
      Moreover, sugar in medicines makes them palatable and bitter medicines inevitably
      affect compliance with the prescribed treatment. Poor compliance leads to
      inadequate treatment of illness and consequently increases the risk of
      complications from illness. Hence sugar-free medicines promoted as a public
      health policy could have actually caused more harm than any meaningful net
      benefit. There is an urgent need for a healthy debate and a fresh look at the
      policy of promoting sugar-free medicines.

PMID- 22955757
TI  - Oral diagnosis and treatment planning: part 5. Preventive and treatment planning
      for dental caries.
AB  - The practice of operative dentistry continues to evolve, to reflect the many
      changes occurring in society and in dental diseases and conditions. However, the
      belief that all questionable and early carious lesions should be restored still
      persists. This belief is largely based upon the concept that the removal of all
      carious tissue followed by meticulous restoration of the tooth is the treatment
      of choice for dental caries. Yet restorations are not permanent and do not cure
      caries, as the causes remain. On the other hand, preventive measures can remove
      or partially remove the causes, thereby reducing the risks for future caries
      recurrence at the same site or elsewhere in the mouth.

PMID- 22955758
TI  - Atypical pattern of (meth)acrylate allergic contact dermatitis in dental
      professionals.
AB  - (Meth)acrylates in dental bonding agents are a common source of allergic contact
      dermatitis in dental professionals. The distribution of the contact dermatitis is
      commonly on finger tips, but is determined by individual habits as demonstrated
      by the two case reports in this article. Despite the site of contact dermatitis,
      the bonding agents are often not suspected as a source of contact allergy due to
      misconception regarding the protective effect of natural rubber latex gloves.
      With these case reports, we endeavour to emphasize the inadequacy of the latex
      gloves in protecting against the (meth)acrylate induced contact allergy and also
      list the measures a dental professional needs to incorporate in order to minimise
      the risks of sensitisation to (meth)acrylates.

PMID- 22955763
TI  - Summary of: evaluation of the end user (dentist) experience of undertaking
      clinical audit in the post April 2001 general dental services (GDS) scheme.

PMID- 22955764
TI  - Summary of: the effects of NICE guidelines on the management of third molar
      teeth.

PMID- 22955765
TI  - Defibrillation in the dental practice.
AB  - A large number of cardiac arrests occur outside hospital each year in the UK and
      as rapid defibrillation plays an integral role in survival rates, it can be seen
      as all healthcare premises' responsibility to have immediate access to an
      automated external defibrillator (AED). This article looks at the importance of
      the AED and the dental practice in emergency resuscitation, and national
      guidelines.

PMID- 22955766
TI  - The Royal Colleges, the LDS and the struggles of the dental profession.
AB  - This paper is based on a lecture to the symposium on 'apprenticeship to life long
      learning: dental education through the centuries', Centre for the History of
      Medicine, University of Glasgow.

PMID- 22955783
TI  - Jimmy Steele: 'it's not as if we are going to run out of work'. Interview by Ruth
      Doherty.

PMID- 22955789
TI  - Evaluation of the end user (dentist) experience of undertaking clinical audit in
      the post April 2001 general dental services (GDS) scheme.
AB  - INTRODUCTION: A mandatory scheme for clinical audit in the general dental
      services (GDS) was launched in April 2001. No evaluation of this mandatory scheme
      exists in the literature. This study provides an evaluation of this scheme. More
      recently a new dental contract was introduced in the general dental services
      (GDS) in April 2006. Responsibility for clinical audit activities was devolved to
      primary care trusts (PCTs) as part of their clinical governance remit. METHODS:
      All GDPs within Essex were contacted by letter and invited to participate in the
      research. A qualitative research method was selected for this evaluation,
      utilising audio-taped semi-structured research interviews with eight general
      dental practitioners (GDPs) who had taken part in the GDS clinical audit scheme
      and who fitted the sampling criteria and strategy. The evaluation focused on
      dentists' experiences of the scheme. RESULTS: The main findings from the analysis
      of the GDS scheme data suggest that there is clear evidence of change following
      audit activities occurring within practices and for the benefit of patients.
      However, often it is the dentist only that undertakes a clinical audit project
      rather than the dental team, there is a lack of dissemination of project findings
      beyond the individual participating practices, very little useful feedback
      provided to participants who have completed a project and very limited use of
      formal re-auditing of a particular topic. CONCLUSIONS: This study provides
      evaluation of the GDS clinical audit scheme. Organisations who propose to
      undertake clinical audit activities in conjunction with dentistry in the future
      may benefit from incorporating and/or developing some findings from this
      evaluation into their project design and avoiding others.

PMID- 22955790
TI  - The effects of NICE guidelines on the management of third molar teeth.
AB  - BACKGROUND: Third molar surgery (TMS) is probably one of the most commonly
      performed surgical procedures undertaken in the NHS. In 2000, the National
      Institute of Clinical Excellence (NICE) introduced guidelines relating to TMS.
      These recommended against the prophylactic removal of third molars and listed
      specific clinical indications for surgery. The impact of these guidelines has not
      been fully evaluated and this research hopes to focus the effect of these
      guidelines over the last ten years. METHODS: Using data obtained from a variety
      of NHS databases such as HES (Eng & Wales), the NHSBSA and data from NHS
      Scotland, we looked at the age range of patients requiring third molar removal
      and the number of patients having third molars removed in both primary and
      secondary care environments from 1989 to 2009. In addition we looked at the
      clinical indications for TMS activity in secondary care. FINDINGS: The mean age
      of patients increased from 25 years in 2000 to 32 years in 2010, with the modal
      (most common) age increasing from 26 to 29 years. After the introduction of
      clinical guidelines the number of patients requiring third molar removal in
      secondary care dropped by over 30%, however, since 2003 the number of patients
      has risen by 97%. There is also a significant increase in caries as an indication
      for third molar removal. CONCLUSIONS: More patients are requiring third molar
      removal with an increasing number of patients having caries related to their
      third molars. Patients are, on average, older confirming that the removal of
      third molars is shifting from a young adult population group to an older adult
      population group. NICE guidelines did appear to have contributed to a fall in the
      volume of third molars removed within the NHS post 2000. However, concluding that
      this reduction demonstrates the success of NICE's guidance would be a premature
      assumption. The number of patients now requiring third molar removal is
      comparable to that of the mid 1990s. NICE has influenced the management of
      patients with third molars but this has not resulted in any reduction in the
      number of patients requiring third molar removal. Coding and data collection for
      third molars is not uniform, leading to potential misrepresentation of data. This
      perhaps raises the issue that an improved universal coding system is required for
      the NHS and that the NICE guidelines need review.

PMID- 22955791
TI  - Effect of topically applied minoxidil on the survival of rat dorsal skin flap.
AB  - BACKGROUND: Flap necrosis still is a challenging problem in reconstructive
      surgery that results in irreversible tissue loss. This study evaluated the effect
      of topically applied minoxidil on angiogenesis and survival of a caudally based
      dorsal rat skin flap. METHODS: For this study, 24 male Wistar rats were randomly
      divided into three groups of eight each. A caudally based dorsal skin flap with
      the dimensions of 9 * 3 cm was raised. After elevation of the flaps, they were
      sutured back into their initial positions. In group 1 (control group), 1 ml of
      isotonic saline was applied topically to the flaps of all the animals for 14
      days. In group 2, minoxidil solution was spread uniformly over the flap surface
      for 7 days after the flap elevation. In group 3, minoxidil solution was applied
      topically to the flap surface during a 14-day period. On day 7 after the flap
      elevation, the rats were killed. The average area of flap survival was determined
      for each rat. Subdermal vascular architecture and angiogenesis were evaluated
      under a light microscope after two full-thickness skin biopsy specimens had been
      obtained from the midline of the flaps. RESULTS: The lowest flap survival rate
      was observed in group 1, and no difference was observed between groups 1 and 2.
      Compared with groups 1 and 2, group 3 had a significantly increased percentage of
      flap survival (P < 0.05). Intense and moderate angiogenesis also was observed
      respectively at the proximal and distal areas of the flaps in group 3.
      CONCLUSIONS: The results of this experiment seem to show that the early effect of
      minoxidil is vasodilation and that prolonged use before flap elevation leads to
      angiogenesis, increasing flap viability. LEVEL OF EVIDENCE III: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 22955792
TI  - A study of postural changes after breast reduction.
AB  - BACKGROUND: Numerous factors such as the equilibrium of body masses and
      psychological status influence human posture. Breast reduction, on the one hand,
      produces a sudden change in this equilibrium, and on the other hand, it can
      modify the psychological status, significantly improving body image and self
      esteem. This study aimed to assess postural changes after breast reduction by
      studying the position and orientation in space of the body and center of
      pressure. METHODS: The study enrolled 52 patients with breast hypertrophy
      scheduled to undergo breast reduction. Posture was evaluated before surgery and
      during the first year after surgery by quantifying the centers of mass using the
      Fastrak system and the center of pressure using stabilometry. The Wilcoxon signed
      rank sum test was used to detect any changes. RESULTS: Retropositioning of the
      upper part of the body, confirmed by baropodometric analysis, was observed in the
      early postoperative period. The biomechanical system subsequently stabilized,
      reaching equilibrium 1 year after surgery. CONCLUSIONS: The authors believe that
      postural changes after breast reduction are due to changes in body mass as well
      as to the effects of physical and psychological factors on posture. Indeed,
      breast hypertrophy often is associated with kyphosis as patients try to hide what
      they consider to be a source of embarrassment. A new breast eliminates previous
      dissatisfaction with body image, reduces anxiety, and increases self-esteem.
      Improvements in body image and reduced weight in the anterior part of the body
      help to correct this postural disorder. LEVEL OF EVIDENCE II: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 22955793
TI  - Genomics: users' guide to the human genome.

PMID- 22955794
TI  - Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in
      ischemic heart disease patients in the South Indian Tamilian population.
AB  - BACKGROUND: The antiplatelet activity of clopidogrel is variable among patients
      suffering from ischemic heart disease. Variation in the cytochrome P450 2C19
      (CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of
      this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which
      plays a role in the conversion of the prodrug clopidogrel to its active
      metabolite, is genetically influenced by polymorphisms in its gene. The aim of
      our study was to evaluate the association of CYP2C19 polymorphisms and the
      antiplatelet effect of clopidogrel in the South Indian Tamilian population.
      MATERIALS AND METHODS: Genotyping and platelet aggregation results of 149
      ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily
      dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the
      PCR-restriction fragment length polymorphism method. We measured residual
      platelet activities in these patients on clopidogrel therapy in terms of
      impedance (expressed as ohms). The study subjects were divided into two
      metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM);
      group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype,
      and the residual platelet activities were compared. Higher values of impedance
      denote increased residual platelet activity. RESULTS: Poor/intermediate
      metabolizers had significantly higher impedance values than EM/URM [(median;
      range) 4.0; 0-13 vs. 2.0; 0-11, respectively; p = 0.04]. These higher impedance
      values denote higher residual platelet activities among the carriers of loss-of
      function alleles (CYP2C19*2,*3) than among non-carriers. However, residual
      platelet activities were lower among the carriers of the gain-of-function allele
      (CYP2C19*17) than among non-carriers, although this difference was not
      significant. CONCLUSION: Patients with CYP2C19 (*2 or *3) genetic polymorphisms
      had higher residual platelet activities and were associated with a reduced
      antiplatelet response to clopidogrel. As the South Indian Tamilian population is
      characterized with higher frequencies of these genetic polymorphisms, our
      findings mandate further studies aimed at initiating genome-based personalized
      antiplatelet therapy.

PMID- 22955796
TI  - Integrated capture, transport, and magneto-mechanical resonant sensing of
      superparamagnetic microbeads using magnetic domain walls.
AB  - An integrated platform for the capture, transport, and detection of individual
      superparamagnetic microbeads is described for lab-on-a-chip biomedical
      applications. Magnetic domain walls in magnetic tracks have previously been shown
      to be capable of capturing and transporting individual beads through a fluid at
      high speeds. Here it is shown that the strong magnetostatic interaction between a
      bead and a domain wall leads to a distinct magneto-mechanical resonance that
      reflects the susceptibility and hydrodynamic size of the trapped bead. Numerical
      and analytical modeling is used to quantitatively explain this resonance, and the
      magneto-mechanical resonant response under sinusoidal drive is experimentally
      characterized both optically and electrically. The observed bead resonance
      presents a new mechanism for microbead sensing and metrology. The dual
      functionality of domain walls as both bead carriers and sensors is a promising
      platform for the development of lab-on-a-bead technologies.

PMID- 22955795
TI  - Upper gastrointestinal bleeding associated with NSAIDs, other drugs and
      interactions: a nested case-control study in a new general practice database.
AB  - AIM: To test the ability a new Spanish primary care research database (BIFAP) to
      capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs
      and other drugs and compare the results with previous studies. METHODS: We
      performed a nested case-control study in persons aged 40-90 years old included in
      the period 2001-2005. Potential cases were selected through a computer search
      followed by an individual blinded review. Controls matched for age, sex and
      calendar year were randomly selected. The exposure window was defined as 0-30
      days before the index date. Adjusted odds ratios were obtained through
      unconditional logistic regression models. RESULTS: In a study cohort of 669,115
      subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases.
      Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41
      2.09), metamizole (1.52; 1.09-2.13), low-dose aspirin (1.74; 1.37-2.21), other
      antiplatelet drugs (1.73; 1.27-2.36), and oral anticoagulants (2.00; 1.44-2.77).
      We did not find an increased risk with current use of oral corticosteroids (1.11;
      0.66-1.86), SSRIs (1.05; 0.77-1.42), or paracetamol (1.00; 0.82-1.23). Acid
      suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39-0.85),
      particularly in users with antecedents of peptic ulcer (0.16; 0.05-0.58). We
      detected a decreasing time-trend in the relative risk and the population
      attributable proportion associated with NSAIDs over the study period.
      CONCLUSIONS: The increased risk of UGIB associated with NSAIDs was lower than
      previously reported, which could partly be explained by methodological
      differences, but a decreasing burden over time of this drug safety problem is
      suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological
      research.

PMID- 22955797
TI  - Automated estimation of abdominal effective diameter for body size normalization
      of CT dose.
AB  - Most CT dose data aggregation methods do not currently adjust dose values for
      patient size. This work proposes a simple heuristic for reliably computing an
      effective diameter of a patient from an abdominal CT image. Evaluation of this
      method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore
      scanners demonstrates close correspondence between computed and manually measured
      patient effective diameters, with a mean absolute error of 1.0 cm (error range
      +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60
      patients on Siemens, General Electric, and Toshiba scanners. A calculated
      effective diameter in the middle slice of an abdominal CT study was found to be a
      close approximation of the mean calculated effective diameter for the study, with
      a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm).
      Furthermore, the mean absolute error for an adjusted mean volume computed
      tomography dose index (CTDIvol) using a mid-study calculated effective diameter,
      versus a mean per-slice adjusted CTDIvol based on the calculated effective
      diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These
      results are used to calculate approximate normalized dose length product values
      in an abdominal CT dose database of 12,506 studies.

PMID- 22955798
TI  - EBV reactivation serological profile in primary Sjogren's syndrome: an underlying
      trigger of active articular involvement?
AB  - Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is
      associated with viral replication. However, their possible associations with
      clinical/therapeutic features in primary Sjogren's syndrome (pSS) were not
      established. We evaluated 100 pSS patients (American-European Criteria) and 89
      age/gender/ethnicity-matched healthy controls. Disease activity was measured by
      EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti
      VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients
      and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs.
      86.5 %, p = 0.501; 2.6 +/- 1.1 vs. 2.5 +/- 1.1 AU/mL, p = 0.737) and anti-EBNA-1
      IgG (92 vs. 94.4 %, p = 0.576; 141.3 +/- 69.8 vs. 135.6 +/- 67.5 RU/mL, p =
      0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and
      increased mean levels of anti-EA-D were observed in patients than controls (36
      vs. 4.5 %, p < 0.0001; 38.6 +/- 57.4 vs. 7.9 +/- 26.3 RU/mL, p < 0.0001). Further
      analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed
      comparable age/gender/ethnicity (p >= 0.551), current prednisone dose (4.8 +/-
      6.9 vs. 5.1 +/- 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs.
      37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI
      values were comparable (p = 0.102), but joint activity was more frequent (25 vs.
      9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not
      associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid
      factor (p = 1.000), anti-alpha-fodrin (p = 0.390) or antiphospholipid antibodies
      (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency
      associated with joint activity raises the possibility that a subclinical EBV
      reactivation may trigger or perpetuate the articular involvement in pSS.

PMID- 22955799
TI  - Health-related quality of life in Turkish patients with ankylosing spondylitis:
      impact of peripheral involvement on quality of life in terms of disease activity,
      functional status, severity of pain, and social and emotional functioning.
AB  - Ankylosing spondylitis (AS) affects sacroiliac joints at early stages and may
      involve the axial skeleton at later stages of disease. Peripheral involvement
      usually occurs in lower extremities. When it develops early in the disease
      course, it is a predictor of more aggressive disease. The aim of this study is to
      evaluate health-related quality of life (HRQoL) in AS and to assess the impact of
      peripheral involvement on HRQoL domains in terms of disease activity, functional
      status, pain, and social and emotional functioning. Seventy-four AS patients were
      included. Peripheral involvement was present in 51.35 % of the patients. In 65.79
      % of these cases the hips, in 31.58 % the knees, in 18.42 % the shoulders and in
      13.16 % the ankles were affected. Patients were evaluated by Ankylosing
      Spondylitis Quality of Life (ASQoL), Short Form-36 (SF-36), Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease
      Activity Score (ASDAS) and Bath Ankylosing Spondylitis Functional Index (BASFI).
      ASQoL was strongly correlated with ASDAS, BASDAI, BASFI, and Bath Ankylosing
      Spondylitis Metrology Index (BASMI), severity of total pain, night pain, fatigue,
      morning stiffness and ESR. ASDAS and BASDAI showed the strongest correlation with
      ASQoL. Severity of total pain, functional status and severity of night pain
      followed it, respectively. Patients with peripheral involvement scored
      significantly lower in all subgroups of SF36 and significantly higher in ASDAS,
      BASDAI, BASFI, BASMI and ASQoL scores and levels of pain, night pain, fatigue and
      morning stiffness. Peripheral involvement is associated with more active disease
      and functional disability and has a negative influence on HRQoL including
      physical, social and emotional functioning.

PMID- 22955800
TI  - The relationship between Knee Injury and Osteoarthritis Outcome Score (KOOS) and
      Timed Up and Go test in patients with symptomatic knee osteoarthritis.
AB  - Both self-reported and physical performance tests are used as outcome measures in
      knee osteoarthritis (OA). The aim of this study is to investigate the
      relationship between Knee Injury and Osteoarthritis Outcome Score (KOOS) and
      Timed Up and Go (TUG) test in the patients with symptomatic knee OA. Eighty-nine
      patients with symptomatic knee OA who admitted to the outpatient clinic of the
      hospital were included in the study. All patients had bilateral medial
      tibiofemoral knee OA. After physical examination, radiological severity of the
      disease was evaluated with Kellgren-Lawrence scale. All patients completed KOOS
      that is a knee-related disorder-specific questionnaire. TUG test was used for the
      evaluation of performance-based functional status. Seventy-seven patients (84.5
      %) were female. Mean age was 62.9 +/- 9.5 (50-85) years, and body mass index was
      32.10 +/- 4.39 kg/m(2). Mean symptom duration was 7.08 +/- 6.52 years. Mean
      radiological stage was 3.22 +/- 0.69. There was a statistically significant
      negative correlation between all of the KOOS domains and TUG (p < 0.01). As a
      result of this study, a moderate relationship was found between the all KOOS
      dimensions and TUG in knee OA.

PMID- 22955801
TI  - Severe hypercalcemia after a single high dose of vitamin D in a patient with
      sarcoidosis.

PMID- 22955802
TI  - [Focus on the person].

PMID- 22955803
TI  - Planning career paths for Ph.D.s.

PMID- 22955808
TI  - Astronomy. World-class observatory rising on 'roof of the world'.

PMID- 22955809
TI  - Particle physics. Fermilab looks abroad for help with neutrino experiment.

PMID- 22955810
TI  - Cardiovascular disease. Massive trials to test inflammation hypothesis.

PMID- 22955811
TI  - Genomics. ENCODE project writes eulogy for junk DNA.

PMID- 22955812
TI  - Global research universities. Flocking to Asia for a shot at greatness.

PMID- 22955813
TI  - Global research universities. A life outside work.

PMID- 22955814
TI  - Profile: Ewan Birney. Genomics' big talker.

PMID- 22955815
TI  - Prions: a piece of the puzzle?

PMID- 22955817
TI  - Life in science. Respect in a pinch.

PMID- 22955816
TI  - Sustaining metal-loving plants in mining regions.

PMID- 22955818
TI  - Comment on "Orthographic processing in baboons (Papio papio)".
AB  - Grainger et al. (Reports, 13 April 2012, p. 245) suggest that baboons can
      discriminate words from nonwords on the basis of two-letter (bigram) frequencies.
      This ability can also be attributed to baboons being able to recognize specific
      letters (i.e., shapes) in specific positions in their four-letter words, without
      reference to letter or bigram frequencies.

PMID- 22955820
TI  - Science and society. Rebuilding public trust in science for policy-making.

PMID- 22955821
TI  - Cell biology. A scaffold switch to insulate.

PMID- 22955822
TI  - Genetics. A GPS for navigating DNA.

PMID- 22955823
TI  - Evolution. Real fish attack simulated plankton.

PMID- 22955824
TI  - Cell biology. Heart brakes.

PMID- 22955825
TI  - Chemistry. Measuring the heaviest atoms.

PMID- 22955826
TI  - Microbiology. Microbial cooperative warfare.

PMID- 22955827
TI  - How cells know the size of their organelles.
AB  - Cells have developed ways to sense and control the size of their organelles. Size
      sensing mechanisms range from direct measurements provided by dedicated reporters
      to indirect functional readouts, and they are used to modify organelle size under
      both normal and stress conditions. Organelle size can also be controlled in the
      absence of an identifiable size sensor. Studies on flagella have dissected
      principles of size sensing and control, and it will be exciting to see how these
      principles apply to other organelles.

PMID- 22955829
TI  - Unconventional sequence of fractional quantum Hall states in suspended graphene.
AB  - Graphene provides a rich platform to study many-body effects, owing to its
      massless chiral charge carriers and the fourfold degeneracy arising from their
      spin and valley degrees of freedom. We use a scanning single-electron transistor
      to measure the local electronic compressibility of suspended graphene, and we
      observed an unusual pattern of incompressible fractional quantum Hall states that
      follows the standard composite fermion sequence between filling factors nu = 0
      and 1 but involves only even-numerator fractions between nu = 1 and 2. We further
      investigated this surprising hierarchy by extracting the corresponding energy
      gaps as a function of the magnetic field. The sequence and relative strengths of
      the fractional quantum Hall states provide insight into the interplay between
      electronic correlations and the inherent symmetries of graphene.

PMID- 22955830
TI  - Electron small polarons and their mobility in iron (oxyhydr)oxide nanoparticles.
AB  - Electron mobility within iron (oxyhydr)oxides enables charge transfer between
      widely separated surface sites. There is increasing evidence that this internal
      conduction influences the rates of interfacial reactions and the outcomes of
      redox-driven phase transformations of environmental interest. To determine the
      links between crystal structure and charge-transport efficiency, we used pump
      probe spectroscopy to study the dynamics of electrons introduced into iron(III)
      (oxyhydr)oxide nanoparticles via ultrafast interfacial electron transfer. Using
      time-resolved x-ray spectroscopy and ab initio calculations, we observed the
      formation of reduced and structurally distorted metal sites consistent with small
      polarons. Comparisons between different phases (hematite, maghemite, and
      ferrihydrite) revealed that short-range structural topology, not long-range
      order, dominates the electron-hopping rate.

PMID- 22955828
TI  - Systematic localization of common disease-associated variation in regulatory DNA.
AB  - Genome-wide association studies have identified many noncoding variants
      associated with common diseases and traits. We show that these variants are
      concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I)
      hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during
      fetal development and are enriched in variants associated with gestational
      exposure-related phenotypes. We identified distant gene targets for hundreds of
      variant-containing DHSs that may explain phenotype associations. Disease
      associated variants systematically perturb transcription factor recognition
      sequences, frequently alter allelic chromatin states, and form regulatory
      networks. We also demonstrated tissue-selective enrichment of more weakly disease
      associated variants within DHSs and the de novo identification of pathogenic cell
      types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait,
      without prior knowledge of physiological mechanisms. Our results suggest
      pervasive involvement of regulatory DNA variation in common human disease and
      provide pathogenic insights into diverse disorders.

PMID- 22955831
TI  - Evidence for NO(x) control over nighttime SOA formation.
AB  - Laboratory studies have established a number of chemical pathways by which
      nitrogen oxides (NO(x)) affect atmospheric organic aerosol (OA) production.
      However, these effects have not been directly observed in ambient OA. We report
      measurements of particulate organic nitrates in Bakersfield, California, the
      nighttime formation of which increases with NO(x) and is suppressed by high
      concentrations of organic molecules that rapidly react with nitrate radical
      (NO(3))--evidence that multigenerational chemistry is responsible for organic
      nitrate aerosol production. This class of molecules represents about a third of
      the nighttime increase in OA, suggesting that most nighttime secondary OA is due
      to the NO(3) product of anthropogenic NO(x) emissions. Consequently, reductions
      in NO(x) emissions should reduce the concentration of organic aerosol in
      Bakersfield and the surrounding region.

PMID- 22955832
TI  - Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during
      meiosis.
AB  - Meiotic recombination in budding yeast requires two RecA-related proteins, Rad51
      and Dmc1, both of which form filaments on DNA capable of directing homology
      search and catalyzing formation of homologous joint molecules (JMs) and strand
      exchange. With use of a separation-of-function mutant form of Rad51 that retains
      filament-forming but not JM-forming activity, we show that the JM activity of
      Rad51 is fully dispensable for meiotic recombination. The corresponding mutation
      in Dmc1 causes a profound recombination defect, demonstrating Dmc1's JM activity
      alone is responsible for meiotic recombination. We further provide biochemical
      evidence that Rad51 acts with Mei5-Sae3 as a Dmc1 accessory factor. Thus, Rad51
      is a multifunctional protein that catalyzes recombination directly in mitosis and
      indirectly, via Dmc1, during meiosis.

PMID- 22955833
TI  - The molecular mechanism of thermal noise in rod photoreceptors.
AB  - Spontaneous electrical signals in the retina's photoreceptors impose a limit on
      visual sensitivity. Their origin is attributed to a thermal, rather than
      photochemical, activation of the transduction cascade. Although the mechanism of
      such a process is under debate, the observation of a relationship between the
      maximum absorption wavelength (lambda(max)) and the thermal activation kinetic
      constant (k) of different visual pigments (the Barlow correlation) indicates that
      the thermal and photochemical activations are related. Here we show that a
      quantum chemical model of the bovine rod pigment provides a molecular-level
      understanding of the Barlow correlation. The transition state mediating thermal
      activation has the same electronic structure as the photoreceptor excited state,
      thus creating a direct link between lambda(max) and k. Such a link appears to be
      the manifestation of intrinsic chromophore features associated with the existence
      of a conical intersection between its ground and excited states.

PMID- 22955834
TI  - Ecological populations of bacteria act as socially cohesive units of antibiotic
      production and resistance.
AB  - In animals and plants, social structure can reduce conflict within populations
      and bias aggression toward competing populations; however, for bacteria in the
      wild it remains unknown whether such population-level organization exists. Here,
      we show that environmental bacteria are organized into socially cohesive units in
      which antagonism occurs between rather than within ecologically defined
      populations. By screening approximately 35,000 possible mutual interactions among
      Vibrionaceae isolates from the ocean, we show that genotypic clusters known to
      have cohesive habitat association also act as units in terms of antibiotic
      production and resistance. Genetic analyses show that within populations, broad
      range antibiotics are produced by few genotypes, whereas all others are
      resistant, suggesting cooperation between conspecifics. Natural antibiotics may
      thus mediate competition between populations rather than solely increase the
      success of individuals.

PMID- 22955836
TI  - [Abstracts of the 64th Congress of the German Society for Urology. September 26
      29, 2012. Leipzig, Germany].

PMID- 22955835
TI  - The influence of stress, depression, and anxiety on PSA screening rates in a
      nationally representative sample.
AB  - BACKGROUND: Prostate-specific antigen (PSA) testing for prostate cancer is
      controversial, with concerning rates of both overscreening and underscreening.
      The reasons for the observed rates of screening are unknown, and few studies have
      examined the relationship of psychological health to PSA screening rates.
      Understanding this relationship can help guide interventions to improve informed
      decision-making for screening. METHODS: A nationally representative sample of men
      57-85 years old without prostate cancer (N = 1169) from the National Social life,
      Health and Aging Project was analyzed. The independent relationship of validated
      psychological health scales measuring stress, anxiety, and depression to PSA
      testing rates was assessed using multivariable logistic regression analyses.
      RESULTS: PSA screening rates were significantly lower for men with higher
      perceived stress [odds ratio (OR) = 0.76, P = 0.006], but not for higher
      depressive symptoms (OR = 0.89, P = 0.22) when accounting for stress. Anxiety
      influences PSA screening through an interaction with number of doctor visits (P =
      0.02). Among the men who visited the doctor once those with higher anxiety were
      less likely to be screened (OR = 0.65, P = 0.04). Conversely, those who visited
      the doctor 10+ times with higher anxiety were more likely to be screened (OR =
      1.71, P = 0.04). CONCLUSIONS: Perceived stress significantly lowers PSA screening
      likelihood, and it seems to partly mediate the negative relationship of
      depression with screening likelihood. Anxiety affects PSA screening rates
      differently for men with different numbers of doctor visits. Interventions to
      influence PSA screening rates should recognize the role of the patients'
      psychological state to improve their likelihood of making informed decisions and
      improve screening appropriateness.

PMID- 22955837
TI  - Surface immobilization of protein via biosilification catalyzed by silicatein
      fused to glutathione S-transferase (GST).
AB  - Silicatein from Suberites domuncula was known to catalyze silica deposition in
      vitro under near neutral pH and ambient temperature conditions. In this study, we
      employed GST-glutathione (GSH) interaction system to increase the production of
      silicatein and develop an efficient protein immobilization method. Recombinant
      silicatein fused with GST (GST-SIL) was produced in E. coli and the GST-SIL
      protein was employed on GSH-coated glass plate. GST-SIL bound surface or matrix
      can catalyze the formation of silica layer in the presence of tetraethyl
      orthosilicate as a substrate at an ambient temperature and neutral pH. During
      silicatein-mediated silicification, green fluorescent protein (GFP) or
      horseradish peroxidase (HRP) can be efficiently immobilized on the silica
      surface. Immobilized GFP or HRP retained their activity and were released
      gradually. This biocompatible silica coating technique can be employed to prepare
      biomolecule-immobilized surfaces or matrixes, which are useful for the
      development of biocatalytic, diagnostic and biosensing system, or tissue culture
      scaffolds.

PMID- 22955838
TI  - FGF2 deficit during development leads to specific neuronal cell loss in the
      enteric nervous system.
AB  - The largest part of the peripheral nervous system is the enteric nervous system
      (ENS). It consists of an intricate network of several enteric neuronal subclasses
      with distinct phenotypes and functions within the gut wall. The generation of
      these enteric phenotypes is dependent upon appropriate neurotrophic support
      during development. Glial cell line-derived neurotrophic factor (GDNF) and
      fibroblast growth factor-2 (FGF2) play an important role in the differentiation
      and function of the ENS. A lack of GDNF or its receptor (Ret) causes intestinal
      aganglionosis in mice, while fibroblast growth factor receptor signaling
      antagonist is identified as regulating proteins in the GDNF/Ret signaling in the
      developing ENS. Primary myenteric plexus cultures and wholemount preparations of
      wild type (WT) and FGF2-knockout mice were used to analyze distinct enteric
      subpopulations. Fractal dimension (D) as a measure of self-similarity is an
      excellent tool to analyze complex geometric shape and was applied to classify the
      subclasses of enteric neurons concerning their individual morphology. As a
      consequence of a detailed analysis of subpopulation variations, wholemount
      preparations were stained for the calcium binding proteins calbindin and
      calretinin. The fractal analysis showed a reliable consistence of subgroups with
      different fractal dimensions (D) in each culture investigated. Seven different
      neuronal subtypes could be differentiated according to a rising D. Within the
      same D, the neurite length revealed significant differences between wild type and
      FGF2-knockout cultures, while the subclass distribution was also altered.
      Depending on the morphological characteristics, the reduced subgroup was supposed
      to be a secretomotor neuronal type, which could be confirmed by calbindin and
      calretinin staining of the wholemount preparations. These revealed a reduction up
      to 40 % of calbindin-positive neurons in the FGF2-knockout mouse. We therefore
      consider FGF2 playing a more important role in the fine-tuning of the ENS during
      development as previously assumed.

PMID- 22955839
TI  - Contribution of the 5-HTTLPR gene by neuroticism on weight gain in male and
      female participants.
AB  - INTRODUCTION: Reduced brain serotonin (5-HT) function is believed to increase the
      risk for eating-related disturbances. Differences in 5-HT vulnerability are
      genetically determined, including a short (S) allele polymorphism in the
      serotonin transporter gene (5-HTTLPR) that is associated with serotonin
      dysfunction and is therefore believed to increase the risk for obesity. However,
      considerable variability has been apparent to replicate these findings.
      OBJECTIVE: Because reduced control of energy intake often results from distress
      and negative mood (emotional eating) and because brain 5-HT controls stress
      adaptation and mood changes, the aim of the current study was to investigate
      whether the S-allele may particularly contribute toward weight gain in cognitive
      stress-vulnerable individuals with high neuroticism. METHODS: A total of 857
      healthy young male and female college students (21.0+/-2.1 years; BMI 19-25
      kg/m(2)) were genotyped for the 5-HTTLPR polymorphism S'/S' (S/S, S/L(G),
      L(G)/L(G)), S'/L' (S/L(a), L(a)/Lg) and L'/L' (L(A)/L(A)) and trait neuroticism.
      The interaction of 5-HTTLPR by neuroticism was assessed on BMI. RESULTS: BMI
      increased significantly as a function of the presence of the S-allele of 5-HTTLPR
      only in high neurotic individuals. CONCLUSION: These results indicate that
      cognitive stress vulnerabilities are critical mediators of the association
      between 5-HTTLPR and body weight.

PMID- 22955840
TI  - Association of schizophrenia with the phenylthiocarbamide taste receptor
      haplotype on chromosome 7q.
AB  - Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined
      primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome
      7q. Results of prior studies examining the ability to taste PTC in patients with
      schizophrenia have been mixed because of the difficulties in measuring PTC taste
      sensitivity behaviorally. In the current study, we examined the TAS2R38 genotypes
      of schizophrenia patients to determine whether the increased prevalence of
      nontasters in this patient population was indicative of a specific genetic
      association. Our a-priori hypothesis was that schizophrenia patients would show
      an increased prevalence of the nontaster phenotype compared with controls. The
      genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38
      were assayed for 176 schizophrenia patients and 229 healthy control individuals,
      and the two-allele haplotypes were estimated. There was an over-representation of
      the major PTC nontaster haplotype among patients of European descent, relative to
      control individuals of similar ancestry. Patients and controls of African
      ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may
      be used to identify subsets of schizophrenia patients who potentially harbor
      vulnerability genes in this region of chromosome 7q.

PMID- 22955841
TI  - Insect biofuel cells using trehalose included in insect hemolymph leading to an
      insect-mountable biofuel cell.
AB  - In this paper, an insect biofuel cell (BFC) using trehalose included in insect
      hemolymph was developed. The insect BFC is based on trehalase and glucose oxidase
      (GOD) reaction systems which oxidize beta-glucose obtained by hydrolyzing
      trehalose. First, we confirmed by LC-MS that a sufficient amount of trehalose was
      present in the cockroach hemolymph (CHL). The maximum power density obtained
      using the insect BFC was 6.07 MUW/cm(2). The power output was kept more than 10 %
      for 2.5 h by protecting the electrodes with a dialysis membrane. Furthermore, the
      maximum power density was increased to 10.5 MUW/cm(2) by using an air diffusion
      cathode. Finally, we succeeded in driving a melody integrated circuit (IC) and a
      piezo speaker by connecting five insect BFCs in series. The results indicate that
      the insect BFC is a promising insect-mountable battery to power environmental
      monitoring micro-tools.

PMID- 22955844
TI  - Tumour immunology: Differing roles for MYD88 in carcinogenesis.

PMID- 22955842
TI  - Consortium biology in immunology: the perspective from the Immunological Genome
      Project.
AB  - Although the field has a long collaborative tradition, immunology has made less
      use than genetics of 'consortium biology', wherein groups of investigators
      together tackle large integrated questions or problems. However, immunology is
      naturally suited to large-scale integrative and systems-level approaches, owing
      to the multicellular and adaptive nature of the cells it encompasses. Here, we
      discuss the value and drawbacks of this organization of research, in the context
      of the long-running 'big science' debate, and consider the opportunities that may
      exist for the immunology community. We position this analysis in light of our own
      experience, both positive and negative, as participants of the Immunological
      Genome Project.

PMID- 22955843
TI  - Unconventional recognition of peptides by T cells and the implications for
      autoimmunity.
AB  - The interaction of antigen-presenting cells with free peptides or a denatured
      protein can give rise to peptide-MHC class II complexes that are distinct from
      those generated after the processing of the whole protein. Such atypical peptide
      MHC complexes can be recognized by unconventional 'type B' T cells that are not a
      component of the normal immune response to proteins. Importantly, these
      unconventional T cells can be found in the setting of autoimmunity. Here, we
      discuss unconventional peptide recognition by type B T cells and consider the
      implications for type 1 diabetes and other autoimmune diseases.

PMID- 22955847
TI  - B cell signalling: Discouraging encounters.

PMID- 22955845
TI  - Immunometabolism: Immune decisions weigh heavily on us.

PMID- 22955848
TI  - Synthesis, optical resolution, absolute configuration, and osteogenic activity of
      cis-pterocarpans.
AB  - A convenient synthesis of natural and synthetic pterocarpans was achieved in
      three steps. Optical resolution of the respective enantiomers was accomplished by
      analytical and semi-preparative HPLC on a chiral stationary phase. For medicarpin
      and its synthetic derivative 9-demethoxymedicarpin, the absolute configuration
      was confirmed by a combination of experimental LC-ECD coupling and quantum
      chemical ECD calculations. (-)-Medicarpin and (-)-9-demethoxymedicarpin are both
      6aR,11aR-configured, and consequently the corresponding enantiomers, (+)
      medicarpin and (+)-9-demethoxymedicarpin, possess the 6aS,11aS-configuration. A
      comparative mechanism study for osteogenic (bone forming) activity of medicarpin
      (racemic versus enantiomerically pure material) revealed that (+)-(6aS,11aS)
      medicarpin (6a) significantly increased the bone morphogenetic protein-2 (BMP2)
      expression and the level of the bone-specific transcription factor Runx-2 mRNA,
      while the effect was opposite for the other enantiomer, (-)-(6aR,11aR)-medicarpin
      (6a), and for the racemate, (+/-)-medicarpin, the combined effect of both the
      enantiomers on transcription levels was observed.

PMID- 22955849
TI  - The collagen prolyl hydroxylases are novel transcriptionally silenced genes in
      lymphoma.
AB  - BACKGROUND: Prolyl hydroxylation is a post-translational modification that
      affects the structure, stability and function of proteins including collagen by
      catalysing hydroxylation of proline to hydroxyproline through action of collagen
      prolyl hydroxylases3 (C-P3H) and 4 (C-P4H). Three C-P3Hs (nomenclature was
      amended according to approval by the HGNC symbols and names at
      http://www.genenames.org/ and Entrez database at
      http://www.ncbi.nlm.nih.gov/gene) leucineproline-enriched proteoglycan (leprecan)
      1 (Lepre1), leprecan-like 1 (Leprel1), leprecan-like 2 (Leprel2) and two paralogs
      Cartilage-Related Protein (CRTAP) and leprecan-like 4 (Leprel4) are found in
      humans. The C-P4Hs are tetrameric proteins comprising a variable alpha subunit,
      encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant beta subunit encoded
      by P4HB. METHODS: We used RT-PCR, qPCR, pyrosequencing, methylation-specific PCR,
      western blotting and immunohistochemistry to investigate expression and
      regulation of the C-P3H and C-P4H genes in B lymphomas and normal bone marrow.
      RESULTS: C-P3H and C-P4H are downregulated in lymphoma. Down-regulation is
      associated with methylation in the CpG islands and is detected in almost all
      common types of B-cell lymphoma, but the CpG islands are unmethylated or
      methylated at lower levels in DNA isolated from normal bone marrow and
      lymphoblastoid cell lines. Methylation of multiple C-P3H and C-P4H genes is
      present in some lymphomas, particularly Burkitt's lymphoma. CONCLUSIONS:
      Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in
      differentiating disease subtypes.

PMID- 22955850
TI  - Quality of life in participants of a CRC screening program.
AB  - BACKGROUND: Little is known about the effect of participating in a colorectal
      cancer (CRC) screening programme on quality of life (QOL), neither for
      participants with a negative nor for those with a positive test result. These
      findings, however, are important to evaluate the impact of CRC screening.
      METHODS: Participants from CRC screening trials were sent a questionnaire, which
      included validated measures on generic health-related QOL, generic anxiety and
      screen-specific anxiety. Both faecal immunochemical test (FIT) and flexible
      sigmoidoscopy (FS) participants, either with negative or positive test results,
      were addressed. RESULTS: The response rate was 73% (1289 out of 1772) for FIT and
      78% (536 out of 689) for FS participants, with mean ages varying from 63-66
      years. Positive FIT participants had worse physical (PCS-12, 47.1 vs 48.3,
      P=0.02), but equal mental QOL scores (MCS-12, 51.1 vs 51.6, P=0.26). Positive and
      negative FS participants had similar QOL scores. Both FIT and FS participants
      with a positive test result reported more screen-specific anxiety than negative
      FIT and FS participants. Positive and negative FS participants had similar
      generic anxiety scores. CONCLUSION: Our findings indicate that the burden of
      participating in CRC screening may be limited. Conducting a prospective study to
      confirm these results is recommended.

PMID- 22955851
TI  - Erythropoietin-driven signalling and cell migration mediated by polyADP
      ribosylation.
AB  - BACKGROUND: Recombinant human erythropoietin (EPO) is the leading biotechnology
      engineered hormone for treatment of anaemia associated with chronic conditions
      including kidney failure and cancer. The finding of EPO receptors on cancer cells
      has raised the concern that in addition to its action in erythropoiesis, EPO may
      promote tumour cell growth. We questioned whether EPO-induced signalling and
      consequent malignant cell manifestation is mediated by polyADP-ribosylation.
      METHODS: Erythropoietin-mediated PARP (polyADP-ribose polymerase-1) activation,
      gene expression and core histone H4 acetylation were examined in UT7 cells, using
      western blot analysis, RT-PCR and immunofluorescence. Erythropoietin-driven
      migration of the human breast epithelial cell line MDA-MB-435 was determined by
      the scratch assay and in migration chambers. RESULTS: We have found that EPO
      treatment induced PARP activation. Moreover, EPO-driven c-fos and Egr-1 gene
      expression as well as histone H4 acetylation were mediated via polyADP
      ribosylation. Erythropoietin-induced cell migration was blocked by the PARP
      inhibitor, ABT-888, indicating an essential role for polyADP-ribosylation in this
      process. CONCLUSIONS: We have identified a novel pathway by which EPO-induced
      gene expression and breast cancer cell migration are regulated by polyADP
      ribosylation. This study introduces new possibilities regarding EPO treatment for
      cancer-associated anaemia where combining systemic EPO treatment with targeted
      administration of PARP inhibitors to the tumour may allow safe treatment with
      EPO, minimising its possible undesirable proliferative effects on the tumour.

PMID- 22955852
TI  - RPN2 expression predicts response to docetaxel in oesophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Neoadjuvant chemotherapy - often using docetaxel in various
      combinatorial regimens - is a standard treatment choice for advanced oesophageal
      squamous cell carcinoma (ESCC) in Japan. However, no useful markers exist that
      predict docetaxel's effects on ESCC. Ribophorin II (RPN2) silencing, which
      reduces glycosylation of P-glycoproteins and decreases membrane localisation,
      promotes docetaxel-dependent apoptosis. We investigated whether RPN2 expression
      in ESCC biopsy specimens could be a predictive biomarker in docetaxel-based
      neoadjuvant chemotherapy. METHODS: We evaluated RPN2 expression
      immunohistochemically in biopsy specimens from 79 patients with node-positive
      ESCC, who received docetaxel-based adjuvant chemotherapy, and compared clinical
      and pathological responses between the RPN2-positive and RPN2-negative groups. We
      also studied susceptibility of RPN2-suppressed ESCC cells to docetaxel. RESULTS:
      The RPN2-negative group had better clinical and pathological responses to
      docetaxel than the RPN2-positive group. We also found RPN2 suppression to alter
      docetaxel susceptibility in vitro. CONCLUSION: Expression of RPN2 in biopsy
      specimens could be a useful predictive marker for response to docetaxel-based
      neoadjuvant chemotherapy in ESCC.

PMID- 22955853
TI  - Dynamic changes of live/apoptotic circulating tumour cells as predictive marker
      of response to sunitinib in metastatic renal cancer.
AB  - BACKGROUND: Recently, we developed an apoptotic assay for expanding the
      monitoring capabilities of the circulating tumour cells (CTC) test during
      therapy. An automated platform for computing CTCs was integrated with a mAb (M30)
      targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early
      apoptosis; we showed that live CTCs were associated with progression, consistent
      with enhanced cell migration and invasion. The test was first applied here to
      mRCC. METHODS: Live/apoptotic CTCs changes were measured in mRCC patients
      receiving first-line Sunitinib and compared with circulating endothelial cell
      (CEC) levels. RESULTS: The presence of EpCAM-positive, live CTCs predicts
      progression in individual mRCC patient, being associated with distant metastasis
      under first-line Sunitinib. Synchronous detection of CTCs and CEC levels
      discloses for the first time an association between their dynamic changes and
      outcome: a rapid increase of the CEC number as early as the first cycle of
      therapy is associated with CTC decrease in non-progressed patients, whereas a
      delayed response of CECs is related to higher CTC values in the progressed group
      indicating treatment failure. CONCLUSION: We demonstrated that a delayed response
      to antiangiogenic treatment indicated by persistent detection of CECs correlates
      with persistent live CTCs and more aggressive disease.

PMID- 22955854
TI  - Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone
      marrow in gastric cancer cases.
AB  - BACKGROUND: We previously reported that bone marrow (BM) was a homing site for
      gastric cancer (GC) cells leading to haematogenous metastases. There has been
      little study that microRNAs regulated pathways in malignant cells or host cells
      in BM, and thereby regulated the progression of GC. METHODS: Both microRNA
      microarray and gene expression microarray analyses of total RNA from BM were
      conducted, comparing five early and five advanced GC patients. We focused on miR
      144-ZFX axis as a candidate BM regulator of GC progression and validated the
      origin of the microRNA expression in diverse cell fractions (EpCAM(+)CD45(-),
      EpCAM(-)CD45(+), and CD14(+)) by magnetic-activated cell sorting (MACS). RESULTS:
      Quantitative reverse-transcriptase (RT)-PCR analysis validated diminished miR-144
      expression in stage IV GC patients with respect to stage I GC patients (t-test,
      P=0.02), with an inverse correlation to ZFX (ANOVA, P<0.01). Luciferase reporter
      assays in five GC cell lines indicated their direct binding and validated by
      western blotting. Pre-miR144 treatment and the resultant repression of ZFX in GC
      cell lines moderately upregulated their susceptibility to 5-fluorouracil
      chemotherapy. In MACS-purified BM fractions, the level of miR-144 expression was
      significantly diminished in disseminated tumour cell fraction (P=0.0005).
      Diminished miR-144 expression in 93 cases of primary GC indicated poor prognosis.
      CONCLUSION: We speculate that disseminated cancer cells could survive in BM when
      low expression of miR-144 permits upregulation of ZFX. The regulation of the miR
      144-ZFX axis in cancer cells has a key role in the indicator of the progression
      of GC cases.

PMID- 22955855
TI  - Macrophage migration inhibitory factor produced by the tumour stroma but not by
      tumour cells regulates angiogenesis in the B16-F10 melanoma model.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) has been proposed as a
      link between inflammation and tumorigenesis. Despite its potentially broad
      influence in tumour biology and prevalent expression, the value of MIF as a
      therapeutic target in cancer remains unclear. We sought to validate MIF in tumour
      models by achieving a complete inhibition of its expression in tumour cells and
      in the tumour stroma. METHODS: We used MIF shRNA-transduced B16-F10 melanoma
      cells implanted in wild-type and MIF-/- C57Bl6 mice to investigate the effect of
      loss of MIF on tumour growth. Cytokine detection and immunohistochemistry (IHC)
      were used to evaluate tumours ex vivo. RESULTS: Macrophage migration inhibitory
      factor shRNA inhibited expression of MIF protein by B16-F10 melanoma cells in
      vitro and in vivo. In vitro, the loss of MIF in this cell line resulted in a
      decreased response to hypoxia as indicated by reduced expression of VEGF. In vivo
      the growth of B16-F10 tumours was inhibited by an average of 47% in the MIF-/-
      mice compared with wild-type but was unaffected by loss of MIF expression by the
      tumour cells. Immunohistochemistry analysis revealed that microvessel density was
      decreased in tumours implanted in the MIF-/- mice. Profiling of serum cytokines
      showed a decrease in pro-angiogenic cytokines in MIF-/- mice. CONCLUSION: We
      report that the absence of MIF in the host resulted in slower tumour growth,
      which was associated with reduced vascularity. While the major contribution of
      MIF appeared to be in the regulation of angiogenesis, tumour cell-derived MIF
      played a negligible role in this process.

PMID- 22955856
TI  - Human papillomavirus vaccination in low-resource countries: lack of evidence to
      support vaccinating sexually active women.
AB  - Vaccines against the human papillomaviruses (HPV) that cause around 70% of
      cervical cancer cases worldwide are highly efficacious when administered before
      infection with the viruses, which occurs soon after initiation of sexual
      activity. Despite recommendations from key public health bodies that the primary
      target population for HPV vaccination should be young adolescent girls, numerous
      articles have suggested widening the target age group to include older adolescent
      girls and adult women. These articles cite evidence of efficacy and cost
      effectiveness when making recommendations, and they rarely take into account the
      difficult resource-allocation issues faced by decision makers in low-income
      countries. Authors and sponsors of these articles are usually from high-income
      countries and sometimes include vaccine manufacturers. This review discusses the
      strengths and weaknesses of several types of evidence offered by these papers in
      support of vaccination of a broad age range of girls and women. It concludes that
      the greatest public health benefit and value for resources will come from
      vaccinating girls before sexual debut and exposure to HPV, particularly in low
      resource areas.

PMID- 22955857
TI  - An examination, with a meta-analysis, of studies of childhood leukaemia in
      relation to population mixing.
AB  - BACKGROUND: Marked influxes of people into rural areas, termed rural population
      mixing (PM), have been associated with excesses of childhood leukaemia (CL),
      consistent with mini-epidemics of a mainly immunising, subclinical infection to
      which CL is a rare response. For such situations of rural PM would promote
      contacts between infected and susceptible individuals, the latter tending to have
      a higher than average prevalence in rural or isolated areas. Confusion has arisen
      from some workers applying the term PM to non-rural situations lacking known
      recent change. METHODS: Available PM studies using the original definition of
      influxes were examined, a meta-analysis carried out of studies of CL in relation
      to exposure to high levels of rural PM, and also a detailed analysis by age
      group. RESULTS: The meta-analysis of 17 studies shows a significant CL excess in
      association with rural PM: overall relative risk (RR) at ages 0-14: 1.57; 95%
      confidence interval 1.44-1.72; at 0-4 years 1.72 (1.54-1.91). This contrasts with
      the absence of an excess of CL in similarly exposed urban areas (RR 1.00; 0.93
      1.07), pointing to a high level of immunity there. The mixed results of studies
      using other definitions of PM were summarised. The excess associated with rural
      PM below age 2 years (RR 1.51; 1.17, 1.92) was not appreciably different from
      that at later childhood ages. CONCLUSION: Much of the inconsistency among studies
      ostensibly about CL and PM reflects the use of definitions other than that
      originally proposed. The broad similarity of the CL excess below age 2 with that
      at older childhood ages is inconsistent with the Greaves' delayed infection
      hypothesis, since any infection underlying the former is difficult to consider as
      delayed.

PMID- 22955859
TI  - First report of a Tunisian CADASIL patient.

PMID- 22955858
TI  - Prescription refill, patient self-report and physician report in assessing
      adherence to oral endocrine therapy in early breast cancer patients: a
      retrospective cohort study in Catalonia, Spain.
AB  - AIMS: To compare different methods in order to assess adherence and persistence
      with oral endocrine therapy in women diagnosed with breast cancer (BC) in
      Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed
      with stage I, II or IIIa BC and positive hormone receptors at six hospitals in
      Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician
      report and patient self-report using a telephone questionnaire. Persistence was
      measured by refill prescriptions. We used the Kappa index to compare adherence
      measures and logistic regression to evaluate adherence-related risk factors.
      RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self
      report) to 94.7% (physician report), depending on the measure used; persistence
      was 74.7% at 5 years of follow-up. Low concordance between measures was observed
      (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence
      than those aged <50 years. Adherence was also associated with: adjuvant
      chemotherapy and sequential hormonal therapy. CONCLUSIONS: Concordance between
      the different measures was remarkably low, indicating the need for further
      research. Adherence is an issue in the management of BC patients taking oral
      drugs, and should be assessed in clinical practice.

PMID- 22955860
TI  - Increased prevalence of hypertension in haemophilia patients.
AB  - An increased prevalence of hypertension is reported in haemophilia patients, but
      data from large, unbiased studies are lacking. The aim of our study was to cross
      sectionally assess the prevalence of hypertension in a large cohort of 701
      haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and
      315 UK haemophilia patients aged 30 years or older were analysed and compared
      with the general age-matched male population. Mean values of up to three BP
      measurements were used when available. Hypertension was defined as BP over 140/90
      mmHg and/or the use of antihypertensive medication. A total of 49% of patients
      had severe haemophilia. Mean age was 49.8 years. The prevalence of hypertension
      was significantly higher in haemophilia patients (49%, 95% confidence interval
      [CI] 45-53) than in the general population (40%, 95% CI 37-43). The prevalence of
      hypertension was higher in patients with severe haemophilia than in those with
      non-severe disease, but similar across haemophilia types and in Dutch and UK
      patients. Multiple BP measurements were available for 70%.The prevalence of
      hypertension was similar in patients with multiple BP measurements and the
      complete cohort. Hypertension was not significantly associated with renal
      function, a history of renal bleeding or with infection with hepatitis C or HIV,
      but it was associated with overweight/obesity and age. In conclusion, the
      prevalence of hypertension is higher in haemophilia patients than in the general
      population. The cause of this increased prevalence is unknown. Blood pressure
      measurements should be part of standard care in haemophilia patients aged 30
      years or older.

PMID- 22955861
TI  - Surgical correction of gynecomastia with minimal scarring.
AB  - BACKGROUND: Gynecomastia is a benign, excessive development of the male breast
      that occurs at an overall incidence of 32-36 %. The authors effectively removed
      peripheral fat tissues with power-assisted liposuction (PAL) and periareolar
      glandular tissues with a cartilage shaver in a series of patients. The small
      periareolar incisions were not easily recognized. METHODS: Between February 2010
      and April 2012, the charts of 15 patients (28 breasts) treated with PAL and a
      cartilage shaver were retrospectively reviewed. RESULTS: The mean volume of fat
      tissue removed with liposuction was 319 mL, and the mean volume of glandular
      tissue removed with the cartilage shaver was 70 mL. The mean follow-up period was
      11.2 months. No infection, nipple-areola complex necrosis, nipple retraction, or
      saucer deformity was encountered in this series. Intraoperative bleeding occurred
      in one patient. Mild asymmetries developed in three patients. CONCLUSIONS: Use of
      PAL and a cartilage shaver for the treatment of gynecomastia allows for effective
      removal of both the fat and the glandular tissue of the breast through a minimal
      periareolar incision. This technique can achieve excellent aesthetic results with
      inconspicuous scarring. LEVEL OF EVIDENCE IV: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 22955862
TI  - Running circular suture technique for reduction mammaplasty and mastopexy.
AB  - BACKGROUND: Many reports have described various technical aspects of reduction
      mammaplasty and mastopexy procedures. The authors present their technique, which
      combines a number of techniques already described in the literature regarding
      repositioning of the nipple-areola complex, reduction of the diameter of the base
      of the breast, and long-term retention of mammary cone projection. This study
      evaluated the results for patients of various ages and phenotypes in terms of
      scar dimensions, breast positioning, and patient satisfaction in the short,
      medium, and long terms. METHODS: Mammaplasty was performed using the inverted T
      technique. The preoperative skin markings differed from those described in the
      literature in that they did not use the future position of the nipple-areola
      complex as the main reference point. A running circular suture was used to fix
      the breast to the pectoralis major fascia and to reduce the diameter of the base
      of the breast, resulting in a reduced horizontal scar in the inframammary fold.
      The skin-marking technique allowed for better postoperative breast symmetry
      regardless of preoperative variations in shape and volume. RESULTS: The outcomes
      were considered satisfactory in the majority of cases by both the patient (p =
      0.78) and the physician (p = 0.58). Adequate fullness of the upper pole was
      maintained in 94.7 % of the breasts. CONCLUSIONS: The described technique results
      in a reduced diameter of the base of the breast, repair of ptosis, repositioning
      of the nipple-areola complex, and long-term upper pole fullness. Complications
      can occur with any technique, but it is important to choose a technique with good
      quality outcomes overall. LEVEL OF EVIDENCE IV: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 22955863
TI  - Dynamical nonstationarity of resting EEGs in patients with attention
      deficit/hyperactivity disorder (AD/HD).
AB  - This study applied dynamical nonstationarity analysis (DNA) to the resting EEGs
      of patients with attention-deficit/hyperactivity disorder (AD/HD). We aimed to
      assess and characterize AD/HD using features based on the local and global
      duration of dynamical microstate. We hypothesized that AD/HD patients would have
      difficulties in maintaining stable cognitive states (e.g., attention deficit and
      impulsivity) and that they would thus exhibit EEGs with temporal dynamics
      distinct from normal controls, i.e., rapidly and frequently changing dynamics. To
      test this hypothesis, we recorded EEGs from 12 adolescent subjects with AD/HD and
      11 age-matched healthy subjects in the resting state with eyes closed and eyes
      open. We found that AD/HD patients exhibited significantly faster changes in
      dynamics than controls in the right temporal region during the eyes closed
      condition, but slower changes in dynamics in the frontal region during the eyes
      open condition. AD/HD patients exhibited a disruption in the rate of change of
      dynamics in the frontotemporal region at rest, probably due to executive and
      attention processes. We suggest that the DNA using complementary local and global
      features based on the duration of dynamical microstates could be a useful tool
      for the clinical diagnosis of subjects with AD/HD.

PMID- 22955864
TI  - A novel fully implantable wireless sensor system for monitoring hypertension
      patients.
AB  - This paper presents a novel fully implantable wireless sensor system intended for
      long-term monitoring of hypertension patients, designed for implantation into the
      femoral artery with computed tomography angiography. It consists of a pressure
      sensor and a telemetric unit, which is wirelessly connected to an extracorporeal
      readout station for energy supply and data recording. The system measures
      intraarterial pressure at a sampling rate of 30 Hz and an accuracy of +/-1.0 mmHg
      over a range of 30-300 mmHg, while consuming up to 300 MUW. A special peel-away
      sheath introducer set was developed to support the implantation procedure. The
      system delivered stable measurements in initial animal trials in sheep, with
      results being in good agreement with reference sensor systems.

PMID- 22955865
TI  - Heel and toe clearance estimation for gait analysis using wireless inertial
      sensors.
AB  - Tripping is considered a major cause of fall in older people. Therefore, foot
      clearance (i.e., height of the foot above ground during swing phase) could be a
      key factor to better understand the complex relationship between gait and falls.
      This paper presents a new method to estimate clearance using a foot-worn and
      wireless inertial sensor system. The method relies on the computation of foot
      orientation and trajectory from sensors signal data fusion, combined with the
      temporal detection of toe-off and heel-strike events. Based on a kinematic model
      that automatically estimates sensor position relative to the foot, heel and toe
      trajectories are estimated. 2-D and 3-D models are presented with different
      solving approaches, and validated against an optical motion capture system on 12
      healthy adults performing short walking trials at self-selected, slow, and fast
      speed. Parameters corresponding to local minimum and maximum of heel and toe
      clearance were extracted and showed accuracy +/- precision of 4.1 +/- 2.3 cm for
      maximal heel clearance and 1.3 +/- 0.9 cm for minimal toe clearance compared to
      the reference. The system is lightweight, wireless, easy to wear and to use, and
      provide a new and useful tool for routine clinical assessment of gait outside a
      dedicated laboratory.

PMID- 22955866
TI  - In vitro oxygen sensing using intraocular microrobots.
AB  - We present a luminescence oxygen sensor integrated with a wireless intraocular
      microrobot for minimally-invasive diagnosis. This microrobot can be accurately
      controlled in the intraocular cavity by applying magnetic fields. The microrobot
      consists of a magnetic body susceptible to magnetic fields and a sensor coating.
      This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence
      material and polystyrene as a supporting matrix, and it can be wirelessly excited
      and read out by optical means. The sensor works based on quenching of
      luminescence in the presence of oxygen. The excitation and emission spectrum,
      response time, and oxygen sensitivity of the sensor were characterized using a
      spectrometer. A custom device was designed and built to use this sensor for
      intraocular measurements with the microrobot. Due to the intrinsic nature of
      luminescence lifetimes, a frequency-domain lifetime measurement approach was
      used. An alternative sensor design with increased performance was demonstrated by
      using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP nanospheres.

PMID- 22955867
TI  - Identification of the parameters of the Beeler-Reuter ionic equation with a
      partially perturbed particle swarm optimization.
AB  - A partially perturbed particle swarm optimization (PPSO) has been proposed for
      identifying the parameters of the Beeler-Reuter (BR) equation from action
      potential data. In the PPSO algorithm, the 63 BR equation parameters are divided
      into groups, and parameter patterns are made from the combination of the groups.
      PPSO enhances the capability of conventional particle swarm optimization (CPSO)
      by partially perturbing the coordinates of the globally best particle with the
      patterns when the searching process is locally confined. "Experimental data" were
      produced for cardiac myocytes simulated by the BR equation and the equation of
      Luo and Rudy (1991), and were used to test the algorithm of PPSO. The test
      results show that PPSO was able to identify the parameters of the BR equation
      effectively for different cardiac myocytes, while still retaining the conceptual
      simplicity and easy implementation of CPSO.

PMID- 22955868
TI  - Structural identifiability and practical applicability of an alveolar recruitment
      model for ARDS patients.
AB  - Patient-specific mathematical models of respiratory mechanics can offer
      substantial insight into patient state and pulmonary dynamics that are not
      directly measurable. Thus, they offer significant potential to evaluate and guide
      patient-specific lung protective ventilator strategies for acute respiratory
      distress syndrome (ARDS) patients. To assure bedside applicability, the model
      must be computationally efficient and identifiable from the limited available
      data, while also capturing dominant dynamics and trends observed in ARDS
      patients. In this study, an existing static recruitment model is enhanced by
      considering alveolar distension and implemented in a novel time-continuous
      dynamic respiratory mechanics model. The model was tested for structural
      identifiability and a hierarchical gradient descent approach was used to fit the
      model to low-flow test responses of 12 ARDS patients. Finally, a comprehensive
      practical identifiability analysis was performed to evaluate the impact of data
      quality on the model parameters. Identified parameter values were physiologically
      plausible and very accurately reproduced the measured pressure responses.
      Structural identifiability of the model was proven, but practical identifiability
      analysis of the results showed a lack of convexity on the error surface
      indicating that successful parameter identification is currently not assured in
      all test sets. Overall, the model presented is physiologically and clinically
      relevant, captures ARDS dynamics, and uses clinically descriptive parameters. The
      patient-specific models show the ability to capture pulmonary dynamics directly
      relevant to patient condition and clinical guidance. These characteristics
      currently cannot be directly measured or established without such a validated
      model.

PMID- 22955869
TI  - Merging person-specific bio-markers for predicting oral cancer recurrence through
      an ontology.
AB  - One of the major problems related to cancer treatment is its recurrence. Without
      knowing in advance how likely the cancer will relapse, clinical practice usually
      recommends adjuvant treatments that have strong side effects. A way to optimize
      treatments is to predict the recurrence probability by analyzing a set of bio
      markers. The NeoMark European project has identified a set of preliminary bio
      markers for the case of oral cancer by collecting a large series of data from
      genomic, imaging, and clinical evidence. This heterogeneous set of data needs a
      proper representation in order to be stored, computed, and communicated
      efficiently. Ontologies are often considered the proper mean to integrate
      biomedical data, for their high level of formality and for the need of
      interoperable, universally accepted models. This paper presents the NeoMark
      system and how an ontology has been designed to integrate all its heterogeneous
      data. The system has been validated in a pilot in which data will populate the
      ontology and will be made public for further research.

PMID- 22955870
TI  - On the effect of body capacitance to ground in tetrapolar bioimpedance
      measurements.
AB  - Tetrapolar bioimpedance measurements on subjects have long been suspected of
      being affected by stray capacitance between the subjects' body and ground. This
      paper provides a circuit model to analyze that effect in the frequency range from
      100 Hz to 1 MHz in order to identify the relevant parameters when impedance is
      measured by applying a voltage and measuring both the resulting current and the
      potential difference between two points on the surface of the volume conductor.
      The proposed model includes the impedance of each electrode and the input
      impedance of the differential voltage amplifier. When common values for the
      circuit parameters are assumed, the simplified model predicts: 1) a frequency
      independent gain (scale factor) error; 2) inductive artifacts, that is, the
      measured impedance increases with increasing frequency and may include positive
      angle phases; and 3) resonance that can affect well below 1 MHz. In addition to
      the stray capacitance to ground, relevant parameters that determine those errors
      are the capacitance of the "low-current" electrode and the input capacitance of
      the differential voltage amplifier. Experimental results confirm those
      theoretical predictions and show effects from several additional resonances above
      1 MHz that also depend on body capacitance to ground.

PMID- 22955871
TI  - Hidden aqueductal stenosis associated to bilateral idiopathic foramina of Monro
      stenosis mimicking a Chiari I malformation? Case report.
AB  - A 39-year old man came to our outpatient clinic with long history of unspecific
      symptoms and signs. Cerebral MRI showed herniation of the cerebellar tonsils of
      more than 1 cm below the foramen magnum and a triventricular hydrocephalus. A
      diagnosis of Chiari I malformation was retained. After an osteo-dural
      decompression of the posterior fossa, post-operative MRI revealed an aqueductal
      stenosis with triventricular hydrocephalus. An endoscopic-third- ventriculostomy
      showed an idiopathic stenosis of the right foramen of Monro. Residual symptoms
      and persistence of biventricular hydrocephalus justified a ventriculo-peritoneal
      shunt. Aqueductal and foramina of Monro stenosis can mimick a Chiari I
      malformation.

PMID- 22955872
TI  - Asymmetric laterality of Chiari type I malformation in patients with non
      syndromic single-suture craniosynostosis.
AB  - BACKGROUND: Chiari type I malformation is a frequent incidental finding commonly
      associated with craniosynostosis. However, there seems to be a paucity of
      literature concerning the asymmetry of tonsillar herniation in patients with non
      syndromic single-suture craniosynostosis. METHODS: To study the asymmetry in this
      cohort, measurements of the right and left tonsils were made from sagittal images
      from both pre-operative and post-operative images from 11 patients with non
      syndromic single-suture craniosynostosis. RESULTS: Pre-operatively, the mean
      difference between the caudal descent of all tonsils ranged from 0 to 7 mm, with
      a mean difference between sides of 2.45 mm. In three cases, cerebellar tonsils
      were symmetrically herniated. Post-operatively, the mean difference between
      caudal descent of all tonsils ranged from 0 to 4 mm, with a mean difference
      between sides of 1.45 mm. Four were symmetrically herniated. In patients with non
      syndromic single-suture craniosynostosis, the tonsillar herniation is asymmetric
      in the majority of cases. CONCLUSIONS: Asymmetry of cerebellar tonsil herniation
      is a frequent finding in this cohort. The right tonsil is more inferiorly located
      in majority of cases, with predominance to the synostotic suture side in
      asymmetric craniosynostosis cases.

PMID- 22955873
TI  - Density functional study of water-gas shift reaction on M3O(3x)/Cu(111).
AB  - Density functional theory (DFT) was employed to study the water dissociation and
      water-gas shift (WGS) reaction on a series of inverse model catalysts,
      M(3)O(3x)/Cu(111) (M = Mg, Ti, Zr, Mo, W; x = 1, 2, 3). It has been found that
      the WGS reaction on Cu can be facilitated by introducing various oxides to lower
      the barrier of water dissociation. Accordingly, the calculated reaction energy
      for water dissociation was used as a scaling descriptor to screen the WGS
      activity of oxide-Cu model catalysts. Our calculations show that the activity
      towards water dissociation decreases in a sequence: Mg(3)O(3)/Cu(111) >
      Zr(3)O(6)/Cu(111) > Ti(3)O(6)/Cu(111) > W(3)O(9)/Cu(111), Mo(3)O(9)/Cu(111). It
      seems that Mg(3)O(3)/Cu(111) is the best WGS catalyst among the systems studied
      here, being able to dissociate water with no barrier. During the process, both Cu
      and oxides participate in the reaction directly. The strong M(3)O(3x)-Cu
      interaction is able to tune the electronic structure of M(3)O(3x) and therefore
      the activity towards water dissociation. Further studies of the overall WGS
      reaction on Mg(3)O(3)/Cu(111) show that water dissociation may not be the key
      step to control the WGS reaction on Mg(3)O(3)/Cu(111) and the removal of H from
      Mg(3)O(3) can be problematic. The strong interaction between H and O from
      Mg(3)O(3) blocks the O sites for further water dissociation and therefore the WGS
      reaction. Our study observes a very different behavior of oxide clusters in such
      small size from the bigger ones supported on Cu(111) and provides new insight
      into the rational design of the WGS catalysts.

PMID- 22955874
TI  - Predicting most probable conformations of a given peptide sequence in the random
      coil state.
AB  - In this work, we present a computational scheme for finding high probability
      conformations of peptides. The scheme calculates the probability of a given
      conformation of the given peptide sequence using the probability distribution of
      torsion states. Dependence of the states of a residue on the states of its first
      neighbors along the chain is considered. Prior probabilities of torsion states
      are obtained from a coil library. Posterior probabilities are calculated by the
      matrix multiplication Rotational Isomeric States Model of polymer theory. The
      conformation of a peptide with highest probability is determined by using a
      hidden Markov model Viterbi algorithm. First, the probability distribution of the
      torsion states of the residues is obtained. Using the highest probability torsion
      state, one can generate, step by step, states with lower probabilities. To
      validate the method, the highest probability state of residues in a given
      sequence is calculated and compared with probabilities obtained from the Coil
      Databank. Predictions based on the method are 32% better than predictions based
      on the most probable states of residues. The ensemble of "n" high probability
      conformations of a given protein is also determined using the Viterbi algorithm
      with multistep backtracking.

PMID- 22955875
TI  - IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis
      clinical manifestations in the northern Italian population.
AB  - To investigate the genetic variability of IL-17A, IL17-RA, IL-23A and IL-23R
      genes on an in-depth phenotypically characterized northern Italian Psoriatic
      arthritis (PsA) case-control cohort, in search for associations specific to
      different PsA clinical sub-phenotypes. We examined 118 patients with PsA
      according to CASPAR criteria (mean age 57 +/- 13, female 38.4 %, mean disease
      duration 13.9 +/- 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5
      %, radiological erosive disease 49 %) compared with 248 controls of the same
      ethnic origin matched for age and sex. The presence of axial disease was defined
      by the clinical axial involvement and/or the presence of radiological alteration
      consistent with spondyloarthropathy according to New York criteria. The presence
      of peripheral disease (arthritis and/or enthesitis) was defined only on clinical
      basis. A total of 40 SNPs, mapping within the genes mentioned above, were
      genotyped in both groups and used to perform association analyses by subdividing
      the PsA sample into subgroups according to different clinical manifestations on
      the basis of axial and peripheral involvements. No differences between patients
      and controls were found in the distribution of the IL-17A, IL17-RA, IL-23A and IL
      23R genes allelic variants. Comparing patients with axial disease versus those
      without, we found that axial manifestations were significantly associated with
      the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p corr =
      0.019, OR 2.63 [95 % CI 1.13-6.16]). No differences in distribution of the
      allelic variants were found comparing patients with versus those without
      peripheral disease or patients with versus without radiological peripheral
      erosions. In PA patients of northern Italian origin, IL-17A, IL17-RA, IL-23A and
      IL-23R genes allelic variants are not associated with disease susceptibility.
      However, a strong association with the IL-23RA rs12401432 GG genotype is
      associated with axial involvement of the disease.

PMID- 22955876
TI  - How much difference does the age at onset make in early arthritis patients?
      Comparison between the ACR 1987 and the ACR/EULAR 2010 classification criteria
      for rheumatoid arthritis at the time of diagnosis.
AB  - The age at onset in early arthritis (EA) may influence the disease activity and
      its evolution. The aim of the current study is to identify possible differences
      regarding the "old" and the "new" classification criteria between patients with
      early-onset and late-onset early arthritis. The study included 64 patients. They
      were divided in two groups, according to the mean age: early-onset EA--less or
      equal than 45 years old (group A) and late-onset EA--over 45 years old (group B).
      The "old" criteria as well as the "new" ones were assessed for all patients, at
      the time of the first visit to the rheumatologist. The initiation of treatment
      with Methotrexate was used as "gold standard" to calculate the sensitivity and
      the specificity of both criteria. "New" criteria were fulfilled in 51% (A) and
      72% of cases (B), while "old" criteria were fulfilled in 37% of patients (A) and
      62% (B). Methotrexate was initiated in 82% of patients (B) and in 51% (A), p =
      0.01. "New" criteria demonstrated a sensitivity of 77.7% (A) and 83.3% (B), while
      "old" criteria had a sensitivity of 50% (A) and 66.6% (B). Patients with late
      onset had significantly higher disease activity scores: 76% (B) versus 40% (A), p
      = 0.04. The sensitivity and the specificity of the "new" criteria for RA are
      comparable in patients with early-onset and late-onset EA, and the sensitivity of
      these criteria is increased compared to the "old" criteria. Patients with late
      onset fulfilling the "old" criteria had poor prognostic factors and higher
      disease activity at the time of diagnosis, which may have possible implications
      for the disease course.

PMID- 22955877
TI  - Intestinal perforation as the initial presentation of Wegener's granulomatosis.

PMID- 22955878
TI  - Tumour necrosis factor-alpha inhibitor-induced hepatic injury in patients with
      rheumatoid arthritis: two case reports and an analysis of the laboratory data
      from the Slovenian national biologicals registry.
AB  - Tumour necrosis factor-alpha (TNF-alpha) inhibitors are widely used in the
      management of patients with rheumatoid arthritis (RA) and spondylarthritides.
      However, TNF-alpha inhibition may lead to adverse events, including liver injury.
      The RA patients are frequently treated with several potentially hepatotoxic drugs
      concomitantly; hence, a causative link between TNF-alpha inhibitors and liver
      injury is usually difficult to establish. We report two cases of RA patients who
      developed histologically manifest liver injury shortly after the introduction of
      treatment with two different TNF-alpha inhibitors. Furthermore, we present the
      analysis of the laboratory data from the BioRx.si registry (the Slovenian
      national registry of rheumatologic patients treated with biologicals) and provide
      evidence that elevated levels of serum aminotransferase can be observed in
      patients treated with TNF-alpha inhibitors. Additionally, our analysis suggests
      no significant differences between the impact of adalimumab and etanercept on
      aminotransferase levels. Although the use of TNF-alpha inhibitors is safe and
      efficient, we suggest that continuous careful monitoring of aminotransferase
      levels in patients treated with these agents is probably warranted. 

PMID- 22955879
TI  - The Wolfe cycle comes full circle.

PMID- 22955880
TI  - Restricted cellular differentiation in cyanobacterial filaments.

PMID- 22955881
TI  - Long-range electron transport in Geobacter sulfurreducens biofilms is redox
      gradient-driven.
AB  - Geobacter spp. can acquire energy by coupling intracellular oxidation of organic
      matter with extracellular electron transfer to an anode (an electrode poised at a
      metabolically oxidizing potential), forming a biofilm extending many cell lengths
      away from the anode surface. It has been proposed that long-range electron
      transport in such biofilms occurs through a network of bound redox cofactors,
      thought to involve extracellular matrix c-type cytochromes, as occurs for
      polymers containing discrete redox moieties. Here, we report measurements of
      electron transport in actively respiring Geobacter sulfurreducens wild type
      biofilms using interdigitated microelectrode arrays. Measurements when one
      electrode is used as an anode and the other electrode is used to monitor redox
      status of the biofilm 15 MUm away indicate the presence of an intrabiofilm redox
      gradient, in which the concentration of electrons residing within the proposed
      redox cofactor network is higher farther from the anode surface. The magnitude of
      the redox gradient seems to correlate with current, which is consistent with
      electron transport from cells in the biofilm to the anode, where electrons
      effectively diffuse from areas of high to low concentration, hopping between
      redox cofactors. Comparison with gate measurements, when one electrode is used as
      an electron source and the other electrode is used as an electron drain, suggests
      that there are multiple types of redox cofactors in Geobacter biofilms spanning a
      range in oxidation potential that can engage in electron transport. The majority
      of these redox cofactors, however, seem to have oxidation potentials too negative
      to be involved in electron transport when acetate is the electron source.

PMID- 22955882
TI  - Mechanism for Hypocretin-mediated sleep-to-wake transitions.
AB  - Current models of sleep/wake regulation posit that Hypocretin (Hcrt)-expressing
      neurons in the lateral hypothalamus promote and stabilize wakefulness by
      projecting to subcortical arousal centers. However, the critical downstream
      effectors of Hcrt neurons are unknown. Here we use optogenetic, pharmacological,
      and computational tools to investigate the functional connectivity between Hcrt
      neurons and downstream noradrenergic neurons in the locus coeruleus (LC) during
      nonrapid eye movement (NREM) sleep. We found that photoinhibiting LC neurons
      during Hcrt stimulation blocked Hcrt-mediated sleep-to-wake transitions. In
      contrast, when LC neurons were optically stimulated to increase membrane
      excitability, concomitant photostimulation of Hcrt neurons significantly
      increased the probability of sleep-to-wake transitions compared with Hcrt
      stimulation alone. We also built a conductance-based computational model of Hcrt
      LC circuitry that recapitulates our behavioral results using LC neurons as the
      main effectors of Hcrt signaling. These results establish the Hcrt-LC connection
      as a critical integrator-effector circuit that regulates NREM sleep/wake behavior
      during the inactive period. This coupling of distinct neuronal systems can be
      generalized to other hypothalamic integrator nuclei with downstream
      effector/output populations in the brain.

PMID- 22955883
TI  - Molecular basis for Nup37 and ELY5/ELYS recruitment to the nuclear pore complex.
AB  - Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs),
      enormous assemblies composed of multiple copies of ~30 different proteins called
      nucleoporins. To unravel the basic scaffold underlying the NPC, we have
      characterized the species-specific scaffold nucleoporin Nup37 and ELY5/ELYS. Both
      proteins integrate directly via Nup120/160 into the universally conserved
      heptameric Y-complex, the critical unit for the assembly and functionality of the
      NPC. We present the crystal structure of Schizosaccharomyces pombe Nup37 in
      complex with Nup120, a 174-kDa subassembly that forms one of the two short arms
      of the Y-complex. Nup37 binds near the bend of the L-shaped Nup120 protein,
      potentially stabilizing the relative orientation of its two domains. By means of
      reconstitution assays, we pinpoint residues crucial for this interaction. In vivo
      and in vitro results show that ELY5 binds near an interface of the Nup120-Nup37
      complex. Complementary biochemical and cell biological data refine and
      consolidate the interactions of Nup120 within the current Y-model. Finally, we
      propose an orientation of the Y-complex relative to the pore membrane, consistent
      with the lattice model.

PMID- 22955884
TI  - The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated
      injury in antimyeloperoxidase glomerulonephritis.
AB  - Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often
      manifests as focal and necrotizing glomerulonephritis and renal failure.
      Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a
      role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is
      uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO
      molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409
      428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing
      glomerulonephritis similar to that seen after whole MPO immunization, when MPO
      was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell
      clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when
      glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and
      LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement
      membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice.
      The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids,
      MPO(415-426), with several critical residues. ANCA-activated neutrophils not only
      induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive
      anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing
      glomerular lesions. These studies identify an immunodominant MPO T-cell epitope
      and redefine how effector responses can induce injury in MPO-ANCA-associated
      microscopic polyangiitis.

PMID- 22955885
TI  - Intrinsically disordered proteins aggregate at fungal cell-to-cell channels and
      regulate intercellular connectivity.
AB  - Like animals and plants, multicellular fungi possess cell-to-cell channels
      (septal pores) that allow intercellular communication and transport. Here, using
      a combination of MS of Woronin body-associated proteins and a bioinformatics
      approach that identifies related proteins based on composition and character, we
      identify 17 septal pore-associated (SPA) proteins that localize to the septal
      pore in rings and pore-centered foci. SPA proteins are not homologous at the
      primary sequence level but share overall physical properties with intrinsically
      disordered proteins. Some SPA proteins form aggregates at the septal pore, and in
      vitro assembly assays suggest aggregation through a nonamyloidal mechanism
      involving mainly alpha-helical and disordered structures. SPA loss-of-function
      phenotypes include excessive septation, septal pore degeneration, and
      uncontrolled Woronin body activation. Together, our data identify the septal pore
      as a complex subcellular compartment and focal point for the assembly of
      unstructured proteins controlling diverse aspects of intercellular connectivity.

PMID- 22955886
TI  - Microbial shifts in the swine distal gut in response to the treatment with
      antimicrobial growth promoter, tylosin.
AB  - Antimicrobials have been used extensively as growth promoters (AGPs) in
      agricultural animal production. However, the specific mechanism of action for
      AGPs has not yet been determined. The work presented here was to determine and
      characterize the microbiome of pigs receiving one AGP, tylosin, compared with
      untreated pigs. We hypothesized that AGPs exerted their growth promoting effect
      by altering gut microbial population composition. We determined the fecal
      microbiome of pigs receiving tylosin compared with untreated pigs using
      pyrosequencing of 16S rRNA gene libraries. The data showed microbial population
      shifts representing both microbial succession and changes in response to the use
      of tylosin. Quantitative and qualitative analyses of sequences showed that
      tylosin caused microbial population shifts in both abundant and less abundant
      species. Our results established a baseline upon which mechanisms of AGPs in
      regulation of health and growth of animals can be investigated. Furthermore, the
      data will aid in the identification of alternative strategies to improve animal
      health and consequently production.

PMID- 22955887
TI  - Monitoring of bioaerosol inhalation risks in different environments using a six
      stage Andersen sampler and the PCR-DGGE method.
AB  - Increasing evidences show that inhalation of indoor bioaerosols has caused
      numerous adverse health effects and diseases. However, the bioaerosol size
      distribution, composition, and concentration level, representing different
      inhalation risks, could vary with different living environments. The six-stage
      Andersen sampler is designed to simulate the sampling of different human lung
      regions. Here, the sampler was used in investigating the bioaerosol exposure in
      six different environments (student dorm, hospital, laboratory, hotel room,
      dining hall, and outdoor environment) in Beijing. During the sampling, the
      Andersen sampler was operated for 30 min for each sample, and three independent
      experiments were performed for each of the environments. The air samples
      collected onto each of the six stages of the sampler were incubated on agar
      plates directly at 26  degrees C, and the colony forming units (CFU) were
      manually counted and statistically corrected. In addition, the developed CFUs
      were washed off the agar plates and subjected to polymerase chain reaction (PCR)
      denaturing gradient gel electrophoresis (DGGE) for diversity analysis. Results
      revealed that for most environments investigated, the culturable bacterial
      aerosol concentrations were higher than those of culturable fungal aerosols. The
      culturable bacterial and fungal aerosol fractions, concentration, size
      distribution, and diversity were shown to vary significantly with the sampling
      environments. PCR-DGGE analysis indicated that different environments had
      different culturable bacterial aerosol compositions as revealed by distinct gel
      band patterns. For most environments tested, larger (>3 MUm) culturable bacterial
      aerosols with a skewed size distribution were shown to prevail, accounting for
      more than 60 %, while for culturable fungal aerosols with a normal size
      distribution, those 2.1-4.7 MUm dominated, accounting for 20-40 %. Alternaria,
      Cladosporium, Chaetomium, and Aspergillus were found abundant in most
      environments studied here. Viable microbial load per unit of particulate matter
      was also shown to vary significantly with the sampling environments. The results
      from this study suggested that different environments even with similar levels of
      total microbial culturable aerosol concentrations could present different
      inhalation risks due to different bioaerosol particle size distribution and
      composition. This work fills literature gaps regarding bioaerosol size and
      composition-based exposure risks in different human dwellings in contrast to a
      vast body of total bioaerosol levels.

PMID- 22955888
TI  - [Increase in skin surface temperature in spinal anesthesia. Predictive value for
      probability of surgical tolerance].
AB  - BACKGROUND: Spinal anesthesia causes sympathetic blockade which leads to changes
      in the local temperature of the skin surface due to hyperemia. MATERIALS AND
      METHODS: These changes in skin temperature were used in a newly developed method
      for estimating the level of analgesia. A total of 11 patients who were scheduled
      for surgical procedures of the lower extremities with symmetrical spinal
      anesthesia were included in the clinical study. By means of an electronic digital
      multi-channel body temperature measurement device with eight high precision
      temperature sensors placed on defined dermatomes, patient skin temperature was
      continuously measured at 2 s intervals and documented before, during and for 45
      min after spinal anesthesia. Simultaneously, a neurological pin-prick test was
      carried on at regular intervals every 2 min on the defined dermatomes to
      calculate the correlation between the effects of analgesia and corresponding
      changes in skin temperature. RESULTS: The analyzed correlations showed that there
      is a minimum of 1.05 degrees C temperature difference before and after spinal
      anesthesia especially on the lower extremities (foot, knee, inguinal) of patient
      dermatomes. The collected data of varying temperature differences were
      systematically evaluated using statistical software which led to a deeper
      understanding of the interdependency between temperature differences at different
      dermatomes. These interdependencies of temperature differences were used to
      develop a systematic analgesia level measurement algorithm. The algorithm
      calculates the skin temperature differences at specified dermatomes to find the
      accurate level of analgesia and also to find the forward and reverse progresses
      of analgesia. The developed mathematical method shows that it is possible to
      predict the level of analgesia up to an accuracy of 95% after spinal anesthesia.
      CONCLUSIONS: Therefore, it can be concluded that systematic processing of skin
      temperature data, collected at defined dermatomes can be used as a promising
      parameter for predicting surgical tolerance. The objective is to improve this
      experimental method with an extended patient population study.

PMID- 22955890
TI  - Discriminative segmentation-based evaluation through shape dissimilarity.
AB  - Segmentation-based scores play an important role in the evaluation of
      computational tools in medical image analysis. These scores evaluate the quality
      of various tasks, such as image registration and segmentation, by measuring the
      similarity between two binary label maps. Commonly these measurements blend two
      aspects of the similarity: pose misalignments and shape discrepancies. Not being
      able to distinguish between these two aspects, these scores often yield similar
      results to a widely varying range of different segmentation pairs. Consequently,
      the comparisons and analysis achieved by interpreting these scores become
      questionable. In this paper, we address this problem by exploring a new
      segmentation-based score, called normalized Weighted Spectral Distance (nWSD),
      that measures only shape discrepancies using the spectrum of the Laplace
      operator. Through experiments on synthetic and real data we demonstrate that nWSD
      provides additional information for evaluating differences between segmentations,
      which is not captured by other commonly used scores. Our results demonstrate that
      when jointly used with other scores, such as Dice's similarity coefficient, the
      additional information provided by nWSD allows richer, more discriminative
      evaluations. We show for the task of registration that through this addition we
      can distinguish different types of registration errors. This allows us to
      identify the source of errors and discriminate registration results which so far
      had to be treated as being of similar quality in previous evaluation studies.

PMID- 22955891
TI  - Automatic aorta segmentation and valve landmark detection in C-arm CT for
      transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure
      to treat severe aortic valve stenosis. As an emerging imaging technique, C-arm
      computed tomography (CT) plays a more and more important role in TAVI on both pre
      operative surgical planning (e.g., providing 3-D valve measurements) and intra
      operative guidance (e.g., determining a proper C-arm angulation). Automatic aorta
      segmentation and aortic valve landmark detection in a C-arm CT volume facilitate
      the seamless integration of C-arm CT into the TAVI workflow and improve the
      patient care. In this paper, we present a part-based aorta segmentation approach,
      which can handle structural variation of the aorta in case that the aortic arch
      and descending aorta are missing in the volume. The whole aorta model is split
      into four parts: aortic root, ascending aorta, aortic arch, and descending aorta.
      Discriminative learning is applied to train a detector for each part separately
      to exploit the rich domain knowledge embedded in an expert-annotated dataset.
      Eight important aortic valve landmarks (three hinges, three commissures, and two
      coronary ostia) are also detected automatically with an efficient hierarchical
      approach. Our approach is robust under all kinds of variations observed in a real
      clinical setting, including changes in the field-of-view, contrast agent
      injection, scan timing, and aortic valve regurgitation. Taking about 1.1 s to
      process a volume, it is also computationally efficient. Under the guidance of the
      automatically extracted patient-specific aorta model, the physicians can properly
      determine the C-arm angulation and deploy the prosthetic valve. Promising
      outcomes have been achieved in real clinical applications.

PMID- 22955892
TI  - Interactive decomposition and mapping of saccular cerebral aneurysms using
      harmonic functions: its first application with "patient-specific" computational
      fluid dynamics (CFD) simulations.
AB  - Recent developments in medical imaging and advanced computer modeling
      simulations) now enable studies designed to correlate either simulated or
      measured "patient-specific" parameters with the natural history of intracranial
      aneurysm i.e., ruptured or unruptured. To achieve significance, however, these
      studies require rigorous comparison of large amounts of data from large numbers
      of aneurysms, many of which are quite dissimilar anatomically. In this study, we
      present a method that can likely facilitate such studies as its application could
      potentially simplify an objective comparison of surface-based parameters of
      interest such as wall shear stress and blood pressure using large multi-patient,
      multi-institutional data sets. Based on the concept of harmonic function/field,
      we present a unified and simple approach for mapping the surface of an aneurysm
      onto a unit disc. Requiring minimal human interactions the algorithm first
      decomposes the vessel geometry into 1) target aneurysm and 2) parent artery and
      any adjacent branches; it, then, maps the segmented aneurysm surface onto a unit
      disk. In particular, the decomposition of the vessel geometry quantitatively
      exploits the unique combination of three sets of information regarding the shape
      of the relevant vasculature: 1) a distance metric defining the spatially varying
      deviation from a tubular characteristic (i.e., cylindrical structure) of a normal
      parent artery, 2) local curvatures and 3) local concavities at the
      junction/interface between an aneurysm and its parent artery. These three sets of
      resultant shape/geometrical data are then combined to construct a linear system
      of the Laplacian equation with a novel shape-sensitive weighting scheme. The
      solution to such a linear system is a shape-sensitive harmonic function/field
      whose iso-lines will densely gather at the border between the normal parent
      artery and the aneurysm. Finally, a simple ranking system is utilized to select
      the best candidate among all possible iso-lines. Quantitative analysis using
      "patient-specific" aneurysm geometries taken from our internal database
      demonstrated that the technique is robust. Similar results were obtained from
      aneurysms having widely different geometries (bifurcation, terminal and lateral
      aneurysms). Application of our method should allow for meaningful, reliable and
      reproducible model-to-model comparisons of surface-based physiological and
      hemodynamic parameters.

PMID- 22955889
TI  - [Aneurysmal subarachnoid hemorrhage].
AB  - Acute subarachnoid hemorrhage (SAH) is a severe and acute life-threatening
      cerebrovascular disease. Approximately 80% of all acute non-traumatic SAHs are
      the result of a ruptured cerebrovascular aneurysm. Despite advances in diagnosis
      and treatment a high morbidity and mortality still exists. Apart from the primary
      cerebral damage there are also secondary complications, such as vasospasm,
      rebleeding, hydrocephalus, cerebral edema or hydrocephalus. For an appropriate
      therapy an understanding of the extensive pathophysiology, the options in
      diagnostics and therapy and the complications of the disease are essential.
      Anesthesiologists are decisively involved in the therapy of the primary and
      secondary damages and subsequently in the outcome as well. This article provides
      an overview of the perioperative and intensive care management of patients with
      SAH.

PMID- 22955893
TI  - In-hospital medication reviews reduce unidentified drug-related problems.
AB  - PURPOSE: To examine the impact of a new model of care, in which a clinical
      pharmacist conducts structured medication reviews and a multi-professional team
      collates systematic medication care plans, on the number of unidentified DRPs in
      a hospital setting. METHODS: In a prospective two-period study, patients admitted
      to an internal medicine ward at the University Hospital of Lund, Sweden, were
      included if they were >= 65 years old, used >= 3 medications on a regular basis
      and had stayed on the ward for >= 5 weekdays. Intervention patients were given
      the new model of care and control patients received conventional care. DRPs were
      then retrospectively identified after study completion from blinded patient
      records for both intervention and control patients. Two pairs of evaluators
      independently evaluated and classified these DRPs as having been
      identified/unidentified during the hospital stay and according to type and
      clinical significance. The primary endpoint was the number of unidentified DRPs,
      and the secondary endpoints were the numbers of unidentified DRPs within each
      type and clinical significance category. RESULTS: The study included a total of
      141 (70 intervention and 71 control) patients. The intervention group benefited
      from a reduction in the total number of unidentified DRPs per patient during the
      hospital stay: intervention group median 1 (1st-3rd quartile 0-2), control group
      9 (6-13.5) (p < 0.001), and also in the number of medications associated with
      unidentified DRPs per patient: intervention group 1 (0-2), control group 8 (5-10)
      (p < 0.001). All sub-categories of DRPs that were frequent in the control group
      were significantly reduced in the intervention group. Similarly, the DRPs were
      less clinically significant in the intervention group. CONCLUSIONS: A multi
      professional team, including a clinical pharmacist, conducting structured
      medication reviews and collating systematic medication care plans proved very
      effective in reducing the number of unidentified DRPs for elderly in-patients.

PMID- 22955894
TI  - The association of ethnicity with electronically measured adherence to inhaled
      corticosteroids in children.
AB  - PURPOSE: To investigate the association of ethnicity with objectively,
      electronically measured adherence to inhaled corticosteroids (ICS) in a
      multicultural population of children with asthma in the city of Amsterdam.
      METHODS: The study was designed as a prospective, observational multicenter study
      in which adherence to ICS and potential risk factors for adherence to ICS were
      measured in a cohort of Moroccan and native Dutch children with asthma.
      Electronic adherence measurements were performed for 3 months per patient using a
      Real Time Medication Monitoring (RTMM) system. Ethnicity and other potential risk
      factors, such as socio-economic status, asthma control and parental medication
      beliefs, were extracted from medical records or parent interviews. The
      association between adherence and ethnicity was analysed using multivariate
      linear regression analysis. RESULTS: A total of 90 children (aged 1-11 years)
      were included in the study and data of 87 children were used for analysis.
      Average adherence to ICS was 49.3 %. Native Dutch children showed higher
      adherence to ICS than Moroccan children (55.9 vs. 42.5 %, respectively; p =
      0.044, univariate analysis). After correction for confounders (>3 annual visits
      to the paediatric outpatient clinic, regular use of a spacer during inhalation),
      the final regression model showed that ethnicity was independently associated
      with adherence (p = 0.028). CONCLUSIONS: In our Western European population of
      inner city children with asthma, poor adherence to ICS was a serious problem, and
      even somewhat more so in ethnic minorities. Paediatricians involved in asthma
      treatment should be aware of these cultural differences in medication-taking
      behaviour, but further studies are needed to elucidate the causal mechanism.

PMID- 22955895
TI  - Laparoscopic distal gastrectomy with intracorporeal handsewn Billroth-I
      anastomosis (ICHSA).
AB  - BACKGROUND: The number of cases of laparoscopic surgery has been increasing.
      Lymph node dissection has been standardized, and the enlarged view provided by
      laparoscopes allows for the procedure to be performed successfully entirely
      within the abdominal cavity, but many cases of reconstruction using the Billroth
      I method are performed under direct vision through a small incision. In this
      study, by placing an anchor thread on a suture line on the lesser curvature of
      the stomach, we simplified the procedure for handsewn anastomosis and safely
      performed gastroduodenal anastomosis at low cost to obtain good results. METHODS:
      From January 2009 to December 2010, we performed handsewn gastroduodenal
      anastomosis in 18 cases. After performing lymph node dissection, the duodenum and
      the stomach were separated using an automatic stapling device. Anchor sutures
      were placed on the suture line of the lesser curvature of the stomach. First, the
      seromuscular layer of the stomach and the seromuscular layer of the duodenum were
      sutured by performing interrupted suturing using an extracorporeal knot-tying
      method. With the stomach and the duodenum in a fixed state, the anastomosis area
      was opened. The thread of the anchor suture was pulled toward the abdominal wall,
      and then all layers of the stomach and the duodenum at the posterior wall were
      continuously sutured. Similarly, for the anterior wall, all layers were
      continuously sutured from the lesser curvature toward the greater curvature.
      RESULTS: We performed this anastomotic procedure in 18 patients with early
      gastric carcinoma. The mean time required for the anastomosis was 64.6 +/- 17.1
      min, and the estimated blood loss was 53.1 +/- 91 g. All operations were
      curative, and the mean number of retrieved lymph node was 27.1 +/- 10.8. A
      nasogastric tube was removed on the first or second day. An upper
      gastrointestinal series performed on postoperative days 5-6 showed no anastomotic
      leakage and normal transit. Oral intake was started on days 6-7. Postoperative
      complications included one case of a ruptured suture, but this was resolved
      through a conservative approach. There was no mortality. Postoperative endoscopy
      revealed that the anastomosis area was extremely soft, and no abnormalities were
      observed. Moreover, the only costs related to the anastomosis were for the thread
      and needles, and although more time was required compared with mechanical
      anastomosis, the cost was extremely low. CONCLUSIONS: We performed gastroduodenal
      anastomosis under a total laparoscopic approach by handsewn. This method is
      economical, because it does not require the use of machinery for anastomosis, and
      the duodenal stump is short. We believe that this method, which can be performed
      in a similar manner even for obese patients, can be used as a standard method of
      anastomosis.

PMID- 22955896
TI  - Intraoperative assessment of esophagogastric junction distensibility during per
      oral endoscopic myotomy (POEM) for esophageal motility disorders.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) is a novel treatment for
      esophageal motility disorders such as achalasia. To date, the extent of the
      myotomy has been determined based on the subjective assessment of the
      endoscopist. We hypothesized that the real-time measurement of esophagogastric
      junction (EGJ) distensibility using a novel functional lumen-imaging probe would
      enable objective evaluation of POEM. METHODS: Patients diagnosed with achalasia
      disorders electively underwent POEM. Using impedance planimetry with a
      transorally inserted functional lumen-imaging probe (EndoFLIP), cross-sectional
      areas (CSA) and distensibilities at the EGJ were measured intraoperatively
      immediately before and after the transoral myotomy (n = 4). All patients
      completed their 6-month follow-up and two patients had repeat distensibility
      tests at this time. Four healthy volunteers served as a control group. RESULTS:
      POEM was successfully performed in all patients (4/4). Premyotomy measurements
      (40-ml fill mode) showed a median diameter of 6.5 mm (range = 5.2-7.9 mm) at the
      narrowest location of the EGJ and was 10.1 mm (7.3-13.2 mm) following POEM. CSA
      increased from 41.5 mm(2) (20-49 mm(2)) to 86 mm(2) (41-137 mm(2)) at a similar
      median intraballoon pressure (40.3 vs. 38.6 mmHg). The increased EGJ
      distensibility (DI, 1.0 vs. 2.4 mm(2)/mmHg) was comparable to that of healthy
      volunteers (2.7 mm(2)/mmHg). CONCLUSION: Functional lumen distensibility measures
      show that POEM can result in an immediate correction of the nonrelaxing lower
      esophageal sphincter, which appears similar to that of healthy controls.
      Intraoperative EGJ profiling may be an important tool to objectively guide the
      needed extent and completeness of the myotomy during POEM.

PMID- 22955897
TI  - Laparoscopic surgical treatment of diaphragmatic endometriosis: a 7-year single
      institution retrospective review.
AB  - BACKGROUND: Diaphragmatic endometriosis is a rare condition that may cause
      invalidating epigastric or thoracic pain and catamenial pneumothorax. During the
      past decades, laparoscopy has been proposed as an optimal tool for diagnosis and
      surgical eradication of the disease. METHODS: We present a retrospective series
      of consecutive patients affected by diaphragmatic endometriosis, treated by
      laparoscopy at our institution, during a period of 7 years. RESULTS: Among 3,008
      patients with pelvic endometriosis, 46 cases with intraoperative diagnosis of
      diaphragmatic endometriosis were identified. Operative findings showed multiple
      diaphragmatic lesions in 32 (69.5 %) patients and single lesions in 14 (30.4 %).
      Diaphragmatic implants were distributed on the right side in 40 (86.9 %)
      patients; in 5 patients (10.8 %) they were bilateral and 1 patient had a single
      lesion on the left hemidiaphragm. Most of the symptomatic patients were treated
      by complete excision of the nodules, whereas only three patients referring right
      upper-quadrant abdominal pain and right shoulder catamenial pain had superficial
      diaphragmatic endometriosis and were treated by diathermocoagulation. CONCLUSION:
      Diaphragmatic endometriosis should be included in the concept of complete
      eradication of endometriosis. This kind of surgery has been shown to be feasible
      and cost-effective; however, it should be managed in a referral center, by an
      expert laparoscopic gynecologist with knowledge of oncological surgical
      techniques, with the support of a general surgeon and a trained anesthesiologist.

PMID- 22955898
TI  - Use of a specially designed partially covered self-expandable metal stent (PSEMS)
      with a 40-mm diameter for the treatment of upper gastrointestinal suture or
      staple line leaks in 11 cases.
AB  - INTRODUCTION: The use of self-expandable stents to treat postoperative leaks and
      fistula in the upper gastrointestinal (GI) tract is an established treatment for
      leaks of the upper GI tract. However, lumen-to-stent size discrepancies (i.e.,
      after sleeve gastrectomy or esophageal resection) may lead to insufficient
      sealing of the leaks requiring further surgical intervention. This is mainly due
      to the relatively small diameter (<=30 mm) of commonly used commercial stents. To
      overcome this problem, we developed a novel partially covered stent with a shaft
      diameter of 36 mm and a flare diameter of 40 mm. METHODS: From September 2008 to
      September 2010, 11 consecutive patients with postoperative leaks were treated
      with the novel large diameter stent (gastrectomy, n = 5; sleeve gastrectomy, n =
      2; fundoplication after esophageal perforation, n = 2; Roux-en-Y gastric bypass,
      n = 1; esophageal resection, n = 1). Treatment with commercially available stents
      (shaft/flare: 23/28 mm and 24/30 mm) had been unsuccessful in three patients
      before treatment with the large diameter stent. Due to dislocation, the large
      diameter stent was anchored in four patients (2* intraoperatively with transmural
      sutures, 2* endoscopically with transnasally externalized threads). RESULTS:
      Treatment was successful in 11 of 11 patients. Stent placement and removal was
      easy and safe. The median residence time of the stent was 24 (range, 18-41) days.
      Stent dislocation occurred in four cases (36 %). It was treated by anchoring the
      stent. Mean follow-up was 25 (range, 14-40) months. No severe complication
      occurred during or after intervention and no patient was dysphagic. CONCLUSIONS:
      Using the novel large diameter, partially covered stent to seal leaks in the
      upper GI tract is safe and effective. The large diameter of the stent does not
      seem to injure the wall of the upper GI tract. However, stent dislocation
      sometimes requires anchoring of the stent with sutures or transnasally
      externalized threads.

PMID- 22955899
TI  - Laparoscopic transperitoneal sublay mesh repair: a new technique for the cure of
      ventral and incisional hernias.
AB  - BACKGROUND: Incisional hernia is a frequent complication after abdominal surgery.
      Today open sublay mesh repair and the laparoscopic intraperitoneal onlay mesh
      repair are the most widely used techniques for its cure. We developed a
      laparoscopic transperitoneal sublay mesh repair for the treatment of small- and
      medium-size ventral and incisional hernias. Outcomes of the new technique and the
      Rives-Stoppa repair were compared. METHODS: This prospective cohort study with a
      control group involved 93 patients. Between 2008 and 2010, 43 patients underwent
      the laparoscopic transperitoneal sublay mesh repair. During the same period of
      time, a control group of 50 patients underwent an open sublay repair after Rives
      and Stoppa. In 2011, all patients were invited for follow-up. This included pain
      assessments and physical examinations with use of ultrasound. RESULTS: The two
      groups were comparable in terms of patient characteristics and hernia data. The
      operating time was slightly longer for the laparoscopic technique. The hospital
      stay was shorter in the laparoscopy group. There was less chronic pain in the
      laparoscopy group, but this difference was not statistically significant. There
      was no significant difference in postoperative complications, use of analgetics,
      foreign body sensation, and paresthesia between the two groups. We found one long
      term hematoma in the laparoscopy group and one seroma in the open group. In this
      series, there were no recurrences and no wound infections. CONCLUSIONS: Our
      initial results indicate that the new laparoscopic transperitoneal sublay mesh
      repair is a safe and effective method for the treatment of small- and medium-size
      ventral and incisional hernias.

PMID- 22955900
TI  - Stricture prevention after extended circumferential endoscopic mucosal resection
      by injecting autologous keratinocytes in the sheep esophagus.
AB  - BACKGROUND: During the past decades, endoscopic mucosal resection (EMR) has been
      developed to treat early intramucosal esophageal cancers and dysplastic Barrett's
      esophagus. The primary drawback of this method is severe postsurgical esophageal
      stricture formation. The purpose of this preclinical study was to assess
      strategies for prevention of this major complication by injecting autologous
      keratinocytes in the EMR mucosal defect in the sheep model. METHODS:
      Circumferential, 6-cm-long EMRs were performed in the esophagus of nine sheep.
      Autologous keratinocytes were harvested 2 weeks before EMR and cultured.
      Circumferential resection consisted of two opposite hemicircumferential
      mucosectomies allowing a widespread resection of 24 cm(2). Immediately after EMR,
      autologous keratinocytes were endoscopically injected in the mucosal defect.
      Animals were sacrificed after 6 months. RESULTS: Circumferential EMRs were
      successfully performed in all animals. There were no intra- or postoperative
      complications. None of the animals developed strictures. All animals were
      sacrificed at 6 months as planned. Histological examinations showed fibrotic
      changes in 10 % (range 0-25 %) of the circumferential muscularis propria interna
      layer and 7.2 % (range 0-25 %) in the muscularis propria externa layer at the
      midportion of the EMR. No circumferential transmural fibrosis was identified.
      CONCLUSIONS: Prevention of stricture formation after extensive (6-cm long)
      circumferential EMR of the sheep esophagus can be achieved by injecting
      autologous keratinocytes into the wound of the resected mucosal segment.

PMID- 22955901
TI  - Action search by example using randomized visual vocabularies.
AB  - Because actions can be small video objects, it is a challenging problem to search
      for similar actions in crowded and dynamic scenes when a single query example is
      provided. We propose a fast action search method that can efficiently locate
      similar actions spatiotemporally. Both the query action and the video datasets
      are characterized by spatio-temporal interest points. Instead of using a unified
      visual vocabulary to index all interest points in the database, we propose
      randomized visual vocabularies to enable fast and robust interest point matching.
      To accelerate action localization, we have developed a coarse-to-fine video
      subvolume search scheme, which is several orders of magnitude faster than the
      existing spatio-temporal branch and bound search. Our experiments on cross
      dataset action search show promising results when compared with the state of the
      arts. Additional experiments on a 5-h versatile video dataset validate the
      efficiency of our method, where an action search can be finished in just 37.6 s
      on a regular desktop machine.

PMID- 22955902
TI  - Segmentation of intracranial vessels and aneurysms in phase contrast magnetic
      resonance angiography using multirange filters and local variances.
AB  - Segmentation of intensity varying and low-contrast structures is an extremely
      challenging and rewarding task. In computer-aided diagnosis of intracranial
      aneurysms, segmenting the high-intensity major vessels along with the attached
      low-contrast aneurysms is essential to the recognition of this lethal vascular
      disease. It is particularly helpful in performing early and noninvasive diagnosis
      of intracranial aneurysms using phase contrast magnetic resonance angiographic
      (PC-MRA) images. The major challenges of developing a PC-MRA-based segmentation
      method are the significantly varying voxel intensity inside vessels with
      different flow velocities and the signal loss in the aneurysmal regions where
      turbulent flows occur. This paper proposes a novel intensity-based algorithm to
      segment intracranial vessels and the attached aneurysms. The proposed method can
      handle intensity varying vasculatures and also the low-contrast aneurysmal
      regions affected by turbulent flows. It is grounded on the use of multirange
      filters and local variances to extract intensity-based image features for
      identifying contrast varying vasculatures. The extremely low-intensity region
      affected by turbulent flows is detected according to the topology of the
      structure detected by multirange filters and local variances. The proposed method
      is evaluated using a phantom image volume with an aneurysm and four clinical
      cases. It achieves 0.80 dice score in the phantom case. In addition, different
      components of the proposed method-the multirange filters, local variances, and
      topology-based detection-are evaluated in the comparison between the proposed
      method and its lower complexity variants. Owing to the analogy between these
      variants and existing vascular segmentation methods, this comparison also
      exemplifies the advantage of the proposed method over the existing approaches. It
      analyzes the weaknesses of these existing approaches and justifies the use of
      every component involved in the proposed method. It is shown that the proposed
      method is capable of segmenting blood vessels and the attached aneurysms on PC
      MRA images.

PMID- 22955903
TI  - Rate-distortion analysis of dead-zone plus uniform threshold scalar quantization
      and its application--part II: two-pass VBR coding for H.264/AVC.
AB  - In the first part of this paper, we derive a source model describing the
      relationship between the rate, distortion, and quantization steps of the dead
      zone plus uniform threshold scalar quantizers with nearly uniform reconstruction
      quantizers for generalized Gaussian distribution. This source model consists of
      rate-quantization, distortion-quantization (D-Q), and distortion-rate (D-R)
      models. In this part, we first rigorously confirm the accuracy of the proposed
      source model by comparing the calculated results with the coding data of JM 16.0.
      Efficient parameter estimation strategies are then developed to better employ
      this source model in our two-pass rate control method for H.264 variable bit rate
      coding. Based on our D-Q and D-R models, the proposed method is of high
      stability, low complexity and is easy to implement. Extensive experiments
      demonstrate that the proposed method achieves: 1) average peak signal-to-noise
      ratio variance of only 0.0658 dB, compared to 1.8758 dB of JM 16.0's method, with
      an average rate control error of 1.95% and 2) significant improvement in
      smoothing the video quality compared with the latest two-pass rate control
      method.

PMID- 22955904
TI  - Bayesian saliency via low and mid level cues.
AB  - Visual saliency detection is a challenging problem in computer vision, but one of
      great importance and numerous applications. In this paper, we propose a novel
      model for bottom-up saliency within the Bayesian framework by exploiting low and
      mid level cues. In contrast to most existing methods that operate directly on low
      level cues, we propose an algorithm in which a coarse saliency region is first
      obtained via a convex hull of interest points. We also analyze the saliency
      information with mid level visual cues via superpixels. We present a Laplacian
      sparse subspace clustering method to group superpixels with local features, and
      analyze the results with respect to the coarse saliency region to compute the
      prior saliency map. We use the low level visual cues based on the convex hull to
      compute the observation likelihood, thereby facilitating inference of Bayesian
      saliency at each pixel. Extensive experiments on a large data set show that our
      Bayesian saliency model performs favorably against the state-of-the-art
      algorithms.

PMID- 22955905
TI  - Multiscale bi-Gaussian filter for adjacent curvilinear structures detection with
      application to vasculature images.
AB  - The intensity or gray-level derivatives have been widely used in image
      segmentation and enhancement. Conventional derivative filters often suffer from
      an undesired merging of adjacent objects because of their intrinsic usage of an
      inappropriately broad Gaussian kernel; as a result, neighboring structures cannot
      be properly resolved. To avoid this problem, we propose to replace the low-level
      Gaussian kernel with a bi-Gaussian function, which allows independent selection
      of scales in the foreground and background. By selecting a narrow neighborhood
      for the background with regard to the foreground, the proposed method will reduce
      interference from adjacent objects simultaneously preserving the ability of
      intraregion smoothing. Our idea is inspired by a comparative analysis of existing
      line filters, in which several traditional methods, including the vesselness,
      gradient flux, and medialness models, are integrated into a uniform framework.
      The comparison subsequently aids in understanding the principles of different
      filtering kernels, which is also a contribution of this paper. Based on some
      axiomatic scale-space assumptions, the full representation of our bi-Gaussian
      kernel is deduced. The popular  gamma-normalization scheme for multiscale
      integration is extended to the bi-Gaussian operators. Finally, combined with a
      parameter-free shape estimation scheme, a derivative filter is developed for the
      typical applications of curvilinear structure detection and vasculature image
      enhancement. It is verified in experiments using synthetic and real data that the
      proposed method outperforms several conventional filters in separating closely
      located objects and being robust to noise.

PMID- 22955906
TI  - Fast positive deconvolution of hyperspectral images.
AB  - In this brief, we provide an efficient scheme for performing deconvolution of
      large hyperspectral images under a positivity constraint, while accounting for
      spatial and spectral smoothness of the data.

PMID- 22955907
TI  - When does computational imaging improve performance?
AB  - A number of computational imaging techniques are introduced to improve image
      quality by increasing light throughput. These techniques use optical coding to
      measure a stronger signal level. However, the performance of these techniques is
      limited by the decoding step, which amplifies noise. Although it is well
      understood that optical coding can increase performance at low light levels,
      little is known about the quantitative performance advantage of computational
      imaging in general settings. In this paper, we derive the performance bounds for
      various computational imaging techniques. We then discuss the implications of
      these bounds for several real-world scenarios (e.g., illumination conditions,
      scene properties, and sensor noise characteristics). Our results show that
      computational imaging techniques do not provide a significant performance
      advantage when imaging with illumination that is brighter than typical daylight.
      These results can be readily used by practitioners to design the most suitable
      imaging systems given the application at hand.

PMID- 22955909
TI  - Abstracts of the 31st Annual European Society of Regional Anaesthesia (ESRA)
      Congress 2012. September 5-8, 2012. Bordeaux, France.

PMID- 22955908
TI  - The relationship between atopic dermatitis and indoor environmental factors: a
      cross-sectional study among Japanese elementary school children.
AB  - OBJECTIVES: This study aimed to determine that home environmental factors were
      associated with atopic dermatitis in Japanese elementary school children.
      METHODS: In this cross-sectional study, a total of 4,254 children in 12 public
      elementary schools in Sapporo city in Hokkaido, Japan were examined. Atopic
      dermatitis was defined using the International Study of Asthma and Allergies in
      Childhood questionnaire. The questionnaires also contained 14 questions about the
      child's home environment. To obtain multivariate-adjusted ORs for atopic
      dermatitis in relation to the home environment, we controlled for possible
      confounders including gender, school grade, parental history of allergies, number
      of siblings, and whether the child was firstborn. The study participants were
      then divided into two groups according to gender, and a stratified analysis was
      performed to obtain adjusted ORs for atopic dermatitis in relation to the home
      environment. RESULTS: The prevalence of atopic dermatitis in our sample was 16.7
      %. Using fully adjusted models, the risk factors for atopic dermatitis were found
      to be the household use of a non-electric heating system without a ventilation
      duct to the outside (compared to the use of an electric heating system), having
      visible mould in the house, having a mouldy odour in the house, and condensation
      on the windowpanes in the house odds ratios (OR 1.25-1.54). In our stratified
      analysis, having visible mould and having a mouldy odour in the house were
      relevantly found to be risk factors for boys (OR 1.28-1.64). However, these
      associations were not found among girls. CONCLUSIONS: To improve children's
      health, further study is needed to corroborate the findings.

PMID- 22955910
TI  - 1,2-Di(phenylethynyl)ethenes with axially chiral, 2,2'-bridged 1,1'-binaphthyl
      substituents: potent cholesteric liquid-crystal inducers.
AB  - Axially chiral, 3,5-dihydro-4H-dinaphtho[2,1-c:1',2'-e]azepine (dinaphthazepine)
      and 1,1'-binaphthyl-2,2'-disulfonimide (dinaphthosulfonimide) moieties were
      rigidly connected via N-p-phenylene linkers to photochemically (E)/(Z)
      isomerisable 1,2-diethynylethene scaffolds. The chemical stability of the
      resulting systems was found to be critically related to the other substituents on
      the central pi-conjugated scaffold. High helical twisting power (HTP), up to 315
      MUm(-1), for the induction of a cholesteric liquid-crystalline phase through
      doping of a nematic phase was measured, resulting from the introduction of the
      chiral, mesogenic 1,1'-binaphthyl motifs. Single crystal X-ray analysis revealed
      that the phenylene spacer is in pi-conjugation with the N-atom of the
      dinaphthazepine but not with the N-atom of the dinaphthosulfonimide moiety. This
      difference in orientation results in visible-transparency in the electronic
      absorption spectrum and higher (E)/(Z)-photoisomerisation quantum yields of the
      dinaphthosulfonimide-derived chiral dopants, as compared to the dinaphthazepine
      systems, which feature intramolecular charge-transfer absorption in the visible
      region.

PMID- 22955912
TI  - Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating
      EPO production and erythropoiesis.
AB  - An endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to
      hydroxylate the alpha subunit of the hypoxia-inducible factor (HIF) in vitro and
      in cultured cells, but nothing is known about its roles in mammalian
      erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor,
      FG-4497, to P4h-tm(-/-) mice. This caused larger increases in serum Epo
      concentration and kidney but not liver Hif-1alpha and Hif-2alpha protein and Epo
      mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower
      in the P4h-tm(-/-) mice than in the wild-type. Similar, but not identical,
      differences were also seen between FG-4497-treated Hif-p4h-2 hypomorphic (Hif-p4h
      2(gt/gt)) and Hif-p4h-3(-/-) mice versus wild-type mice. FG-4497 administration
      increased hemoglobin and hematocrit values similarly in the P4h-tm(-/-) and wild
      type mice, but caused higher increases in both values in the Hif-p4h-2(gt/gt)
      mice and in hematocrit value in the Hif-p4h-3(-/-) mice than in the wild-type.
      Hif-p4h-2(gt/gt)/P4h-tm(-/-) double gene-modified mice nevertheless had increased
      hemoglobin and hematocrit values without any FG-4497 administration, although no
      such abnormalities were seen in the Hif-p4h-2(gt/gt) or P4h-tm(-/-) mice. Our
      data thus indicate that P4H-TM plays a role in the regulation of EPO production,
      hepcidin expression, and erythropoiesis.

PMID- 22955911
TI  - Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment
      resistance in chronic lymphocytic leukemia.
AB  - Stroma induces treatment resistance in chronic lymphocytic leukemia (CLL),
      possibly because of alterations in the BCL-2 family of proteins, which are key
      regulators of apoptosis. We previously developed BH3 profiling, a functional
      assay that assesses mitochondrial depolarization in response to BH3-only
      peptides, to measure "apoptotic priming," the proximity of a cell to the
      apoptotic threshold. In the present study, we use BH3 profiling to show that CLL
      cells from the PB are highly primed. Increased priming is associated with
      improved clinical response and, unexpectedly, with unmutated IGHV status.
      Coculturing CLL cells in vitro with stroma decreases priming. Using matched PB,
      BM, and lymph node compartment samples, we found in vivo that BM-derived CLL
      cells are the least primed. CLL cells cocultured with stroma were treated with
      the PI3K delta-isoform inhibitor CAL-101 (GS1101). CAL-101 caused CLL cell de
      adhesion, leading to increased CLL cell priming. Stimulation of CLL cells with
      anti-IgM or CXCL12 caused decreased priming that could be reversed by CAL-101.
      Our results show that inhibition of stromal interactions leading to displacement
      of CLL cells into the blood by CAL-101 in vivo may increase CLL cell priming,
      suggesting a mechanism by which agents inducing lymphocyte redistribution might
      facilitate improved clinical response when used in combination with other
      therapies.

PMID- 22955913
TI  - Stromal SPARC contributes to the detrimental fibrotic changes associated with
      myeloproliferation whereas its deficiency favors myeloid cell expansion.
AB  - In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells
      toward BM failure. This event is also sustained by detrimental stromal changes,
      such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal
      prognosis. We show that the matricellular protein SPARC contributes to the BM
      stromal response to myeloproliferation. The degree of SPARC expression in BM
      stromal elements, including CD146(+) mesenchymal stromal cells, correlates with
      the degree of stromal changes, and the severity of BM failure characterizing the
      prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc(-/-)
      mice and BM chimeras, we demonstrate that SPARC contributes to the development of
      significant stromal fibrosis in a model of thrombopoietin-induced myelofibrosis.
      We found that SPARC deficiency in the radioresistant BM stroma compartment
      impairs myelofibrosis but, at the same time, associates with an enhanced reactive
      myeloproliferative response to thrombopoietin. The link betwen SPARC stromal
      deficiency and enhanced myeloid cell expansion under a myeloproliferative spur is
      also supported by the myeloproliferative phenotype resulting from the
      transplantation of defective Apc(min) mutant hematopoietic cells into Sparc(-/-)
      but not WT recipient BM stroma. Our results highlight a complex influence of
      SPARC over the stromal and hematopoietic BM response in myeloproliferative
      conditions.

PMID- 22955914
TI  - Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and
      cellular pathogenesis of classical Hodgkin lymphoma.
AB  - The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in
      the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg
      (HRS) tumor cells are rare in the involved lymph node and therefore difficult to
      analyze. Here, by overcoming this technical challenge and performing, for the
      first time, a genome-wide transcriptional analysis of microdissected HRS cells
      compared with other B-cell lymphomas, cHL lines, and normal B-cell subsets, we
      show that they differ extensively from the usually studied cHL cell lines, that
      the lost B-cell identity of cHLs is not linked to the acquisition of a plasma
      cell-like gene expression program, and that Epstein-Barr virus infection of HRS
      cells has a minor transcriptional influence on the established cHL clone.
      Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of
      its histologic subtypes diverged in their similarity to other related lymphomas.
      Unexpectedly, we identified 2 molecular subgroups of cHL associated with
      differential strengths of the transcription factor activity of the NOTCH1, MYC,
      and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of
      several genes potentially highly relevant to lymphoma pathogenesis, including
      silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K
      driven oncogenic pathway.

PMID- 22955915
TI  - Mutational profile and prognostic significance of TP53 in diffuse large B-cell
      lymphoma patients treated with R-CHOP: report from an International DLBCL
      Rituximab-CHOP Consortium Program Study.
AB  - TP53 mutation is an independent marker of poor prognosis in patients with diffuse
      large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin,
      vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the
      rituximab immunochemotherapy era remains undefined. In the present study of a
      large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show
      that those with TP53 mutations had worse overall and progression-free survival
      compared with those without. Unlike earlier studies of patients treated with
      CHOP, TP53 mutation has predictive value for R-CHOP-treated patients with either
      the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we
      identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the
      most critical structures for maintaining p53 function. In contrast, TP53 deletion
      and loss of heterozygosity did not confer worse survival. If gene mutation data
      are not available, immunohistochemical analysis showing > 50% cells expressing
      p53 protein is a useful surrogate and was able to stratify patients with
      significantly different prognoses. We conclude that assessment of TP53 mutation
      status is important for stratifying R-CHOP-treated patients into distinct
      prognostic subsets and has significant value in the design of future therapeutic
      strategies.

PMID- 22955916
TI  - PTH expands short-term murine hemopoietic stem cells through T cells.
AB  - Intermittent parathyroid hormone (iPTH) treatment expands hemopoietic stem and
      progenitor cells (HSPCs), but the involved mechanisms and the affected HSPC
      populations are mostly unknown. Here we show that T cells are required for iPTH
      to expand short-term HSPCs (ST-HSPCs) and improve blood cell engraftment and host
      survival after BM transplantation. Silencing of PTH/PTH-related protein receptor
      (PPR) in T cells abrogates the effects of iPTH, thus demonstrating a requirement
      for direct PPR signaling in T cells. Mechanistically, iPTH expands ST-HSPCs by
      activating Wnt signaling in HSPCs and stromal cells (SCs) through T-cell
      production of the Wnt ligand Wnt10b. Attesting to the relevance of Wnt10b, iPTH
      fails to expand ST-HSPCs in mice with Wnt10b(-/-) T cells. Moreover, iPTH fails
      to promote engraftment and survival after BM transplantation in Wnt10b null mice.
      In summary, direct PPR signaling in T cells and the resulting production of
      Wnt10b play a pivotal role in the mechanism by which iPTH expands ST-HSPCs. The
      data suggest that T cells may provide pharmacologic targets for HSPC expansion.

PMID- 22955917
TI  - Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via
      mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition.
AB  - Malignant cells have a higher nicotinamide adenine dinucleotide (NAD(+)) turnover
      rate than normal cells, making this biosynthetic pathway an attractive target for
      cancer treatment. Here we investigated the biologic role of a rate-limiting
      enzyme involved in NAD(+) synthesis, Nampt, in multiple myeloma (MM). Nampt
      specific chemical inhibitor FK866 triggered cytotoxicity in MM cell lines and
      patient MM cells, but not normal donor as well as MM patients PBMCs. Importantly,
      FK866 in a dose-dependent fashion triggered cytotoxicity in MM cells resistant to
      conventional and novel anti-MM therapies and overcomes the protective effects of
      cytokines (IL-6, IGF-1) and bone marrow stromal cells. Nampt knockdown by RNAi
      confirmed its pivotal role in maintenance of both MM cell viability and
      intracellular NAD(+) stores. Interestingly, cytotoxicity of FK866 triggered
      autophagy, but not apoptosis. A transcriptional-dependent (TFEB) and independent
      (PI3K/mTORC1) activation of autophagy mediated FK866 MM cytotoxicity. Finally,
      FK866 demonstrated significant anti-MM activity in a xenograft-murine MM model,
      associated with down-regulation of ERK1/2 phosphorylation and proteolytic
      cleavage of LC3 in tumor cells. Our data therefore define a key role of Nampt in
      MM biology, providing the basis for a novel targeted therapeutic approach.

PMID- 22955918
TI  - Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells
      correlates with treatment outcome in classical Hodgkin lymphoma.
AB  - In classical Hodgkin lymphoma (CHL), 20%-30% of patients experience relapse or
      progressive disease after initial treatment. The pathogenesis and biology of
      treatment failure are still poorly understood, in part because the molecular
      phenotype of the rare malignant Hodgkin Reed-Sternberg (HRS) cells is difficult
      to study. Here we examined microdissected HRS cells from 29 CHL patients and 5
      CHL-derived cell lines by gene expression profiling. We found significant overlap
      of HL-specific gene expression in primary HRS cells and HL cell lines, but also
      differences, including surface receptor signaling pathways. Using integrative
      analysis tools, we identified target genes with expression levels that
      significantly correlated with genomic copy-number changes in primary HRS cells.
      Furthermore, we found a macrophage-like signature in HRS cells that significantly
      correlated with treatment failure. CSF1R is a representative of this signature,
      and its expression was significantly associated with progression-free and overall
      survival in an independent set of 132 patients assessed by mRNA in situ
      hybridization. A combined score of CSF1R in situ hybridization and CD68
      immunohistochemistry was an independent predictor for progression-free survival
      in multivariate analysis. In summary, our data reveal novel insights into the
      pathobiology of treatment failure and suggest CSF1R as a drug target of at-risk
      CHL.

PMID- 22955919
TI  - HLA-haploidentical bone marrow transplantation with posttransplant
      cyclophosphamide expands the donor pool for patients with sickle cell disease.
AB  - Allogeneic marrow transplantation can cure sickle cell disease; however, HLA
      matched donors are difficult to find, and the toxicities of myeloablative
      conditioning are prohibitive for most adults with this disease. We developed a
      nonmyeloablative bone marrow transplantation platform using related, including
      HLA-haploidentical, donors for patients with sickle cell disease. The regimen
      consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and total
      body irradiation, and graft-versus-host disease prophylaxis with
      posttransplantation high-dose cyclophosphamide, mycophenolate mofetil, and
      tacrolimus or sirolimus. After screening 19 patients, we transplanted 17, 14 from
      HLA-haploidentical and 3 from HLA-matched related donors. Eleven patients
      engrafted durably. With a median follow-up of 711 days (minimal follow up 224
      days), 10 patients are asymptomatic, and 6 patients are off immunosupression.
      Only 1 patient developed skin-only acute graft-versus-host disease that resolved
      without any therapy; no mortality was seen. Nonmyeloablative conditioning with
      posttransplantation high-dose cyclophosphamide expands the donor pool, making
      marrow transplantation feasible for most patients with sickle cell disease, and
      is associated with a low risk of complications, even with haploidentical related
      donors. Graft failure, 43% in haploidentical pairs, remains a major obstacle but
      may be acceptable in a fraction of patients if the majority can be cured without
      serious toxicities.

PMID- 22955920
TI  - Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute
      lymphoblastic leukemia.
AB  - CRLF2 rearrangements, JAK1/2 point mutations, and JAK2 fusion genes have been
      identified in Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia
      (ALL), a recently described subtype of pediatric high-risk B-precursor ALL (B
      ALL) which exhibits a gene expression profile similar to Ph-positive ALL and has
      a poor prognosis. Hyperactive JAK/STAT and PI3K/mammalian target of rapamycin
      (mTOR) signaling is common in this high-risk subset. We, therefore, investigated
      the efficacy of the JAK inhibitor ruxolitinib and the mTOR inhibitor rapamycin in
      xenograft models of 8 pediatric B-ALL cases with and without CRLF2 and JAK
      genomic lesions. Ruxolitinib treatment yielded significantly lower peripheral
      blast counts compared with vehicle (P < .05) in 6 of 8 human leukemia xenografts
      and lower splenic blast counts (P < .05) in 8 of 8 samples. Enhanced responses to
      ruxolitinib were observed in samples harboring JAK-activating lesions and higher
      levels of STAT5 phosphorylation. Rapamycin controlled leukemia burden in all 8 B
      ALL samples. Survival analysis of 2 representative B-ALL xenografts demonstrated
      prolonged survival with rapamycin treatment compared with vehicle (P < .01).
      These data demonstrate preclinical in vivo efficacy of ruxolitinib and rapamycin
      in this high-risk B-ALL subtype, for which novel treatments are urgently needed,
      and highlight the therapeutic potential of targeted kinase inhibition in Ph-like
      ALL.

PMID- 22955921
TI  - IL-7-producing stromal cells are critical for lymph node remodeling.
AB  - Nonhematopoietic stromal cells of secondary lymphoid organs form important
      scaffold and fluid transport structures, such as lymph node (LN) trabeculae,
      lymph vessels, and conduits. Furthermore, through the production of chemokines
      and cytokines, these cells generate a particular microenvironment that determines
      lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important
      stromal cell-derived cytokine that has been considered to be derived mainly from
      T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial
      cells (LECs) are a prominent source of IL-7 both in human and murine LNs. Using
      bacterial artificial chromosome transgenic IL-7-Cre mice, we found that
      fibroblastic reticular cells and LECs strongly up-regulated IL-7 expression
      during LN remodeling after viral infection and LN reconstruction after avascular
      transplantation. Furthermore, IL-7-producing stromal cells contributed to de novo
      formation of LyveI-positive lymphatic structures connecting reconstructed LNs
      with the surrounding tissue. Importantly, diphtheria toxin-mediated depletion of
      IL-7-producing stromal cells completely abolished LN reconstruction. Taken
      together, this study identifies LN LECs as a major source of IL-7 and shows that
      IL-7-producing stromal cells are critical for reconstruction and remodeling of
      the distinct LN microenvironment.

PMID- 22955923
TI  - Splenic proliferative lymphoid nodules distinct from germinal centers are sites
      of autoantigen stimulation in immune thrombocytopenia.
AB  - To understand more specific abnormalities of humoral autoimmunity, we studied 31
      spleens from immune thrombocytopenia (ITP) patients and 36 control spleens.
      Detailed analysis identified at least 2 different splenic structures
      accommodating proliferating B cells, classic germinal centers (GCs), and
      proliferative lymphoid nodules (PLNs). PLNs were characterized by proliferating
      Ki67(+) B cells close to follicular dendritic cells (FDCs) and lacked
      polarization into dark and light zones. As opposed to cells in GCs, proliferating
      B cells in PLN lacked expression of Bcl6. In both PLNs and GCs of ITP spleens,
      the density of T cells was significantly reduced. Both T follicular helper cells
      (T(FH)) and regulatory T cells were reduced within PLNs of ITP spleens suggesting
      a defect of tolerance related to a loss of T-cell control. Within PLNs of ITP,
      but not controls, abundant platelet glycoprotein (GP) IIb/IIIa autoantigens was
      found in IgM containing immune complexes tightly bound to FDCs and closely
      approximated to proliferating B cells. GPIV was found less often, but not in the
      same PLNs as GPIIb/IIIa. Autoantigens were not found in the GCs of ITP or
      controls indicating that PLNs are the sites of autoantigen stimulation in ITP
      potentially related to a lack of control by T cells and/or the present
      autoantigen.

PMID- 22955922
TI  - Transcription and translation are primary targets of Pim kinase inhibitor SGI
      1776 in mantle cell lymphoma.
AB  - Proviral integration site for Moloney murine leukemia virus (Pim) kinases are
      serine/threonine/tyrosine kinases and oncoproteins that promote tumor
      progression. Three isoforms of Pim kinases have been identified and are known to
      phosphorylate numerous substrates, with regulatory functions in transcription,
      translation, cell cycle, and survival pathways. These kinases are involved in
      production, proliferation, and survival of normal B cells and are overexpressed
      in B-cell malignancies such as mantle cell lymphoma (MCL). SGI-1776 is a small
      molecule and Pim kinase inhibitor with selectivity for Pim-1. We hypothesize that
      Pim kinase function can be inhibited by SGI-1776 in MCL and that inhibition of
      phosphorylation of downstream substrates will disrupt transcriptional,
      translational, and cell cycle processes and promote cell death. SGI-1776
      treatment in 4 MCL cell lines resulted in apoptosis induction. Phosphorylation of
      transcription (c-Myc) and translation targets (4E-BP1), tested in Jeko-1 and
      Mino, was declined. Consistent with these data, Mcl-1 and cyclin D1 protein
      levels were decreased. Importantly, similar to cell line data, MCL primary cells
      but not normal cells showed similar inhibition of substrate phosphorylation and
      cytotoxicity from SGI-1776 treatment. Genetic knockdown of Pim-1/Pim-2 affected
      similar proteins in MCL cell lines. Collectively these data demonstrate Pim
      kinases as therapeutic targets in MCL.

PMID- 22955924
TI  - Endocytosis of soluble immune complexes leads to their clearance by FcgammaRIIIB
      but induces neutrophil extracellular traps via FcgammaRIIA in vivo.
AB  - Soluble immune complexes (ICs) are abundant in autoimmune diseases, yet
      neutrophil responses to these soluble humoral factors remain uncharacterized.
      Moreover, the individual role of the uniquely human FcgammaRIIA and
      glycophosphatidylinositol (GPI)-linked FcgammaRIIIB in IC-mediated inflammation
      is still debated. Here we exploited mice and cell lines expressing these human
      neutrophil FcgammaRs to demonstrate that FcgammaRIIIB alone, in the absence of
      its known signaling partners FcgammaRIIA and the integrin Mac-1, internalizes
      soluble ICs through a mechanism used by GPI-anchored receptors and fluid-phase
      endocytosis. FcgammaRIIA also uses this pathway. As shown by intravital
      microscopy, FcgammaRIIA but not FcgammaRIIIB-mediated neutrophil interactions
      with extravascular soluble ICs results in the formation of neutrophil
      extracellular traps (NETs) in tissues. Unexpectedly, in wild-type mice, IC
      induced NETosis does not rely on the NADPH oxidase, myeloperoxidase, or
      neutrophil elastase. In the context of soluble ICs present primarily within
      vessels, FcgammaRIIIB-mediated neutrophil recruitment requires Mac-1 and is
      associated with the removal of intravascular IC deposits. Collectively, our
      studies assign a new role for FcgammaRIIIB in the removal of soluble ICs within
      the vasculature that may serve to maintain homeostasis, whereas FcgammaRIIA
      engagement of tissue soluble ICs generates NETs, a proinflammatory process linked
      to autoimmunity.

PMID- 22955925
TI  - HTLV-1-infected T cells contain a single integrated provirus in natural
      infection.
AB  - Human T lymphotropic virus type 1 (HTLV-1) appears to persist in the chronic
      phase of infection by driving oligoclonal proliferation of infected T cells. Our
      recent high-throughput sequencing study revealed a large number (often > 10(4))
      of distinct proviral integration sites of HTLV-1 in each host that is greatly in
      excess of previous estimates. Here we use the highly sensitive, quantitative high
      throughput sequencing protocol to show that circulating HTLV-1(+) clones in
      natural infection each contain a single integrated proviral copy. We conclude
      that a typical host possesses a large number of distinct HTLV-1-infected T-cell
      clones.

PMID- 22955926
TI  - Profound metabolic, functional, and cytolytic differences characterize HIV
      specific CD8 T cells in primary and chronic HIV infection.
AB  - Immediate-early host-virus interactions that occur during the first weeks after
      HIV infection have a major impact on disease progression. The mechanisms
      underlying the failure of HIV-specific CD8 T-cell response to persist and control
      viral replication early in infection are yet to be characterized. In this study,
      we performed a thorough phenotypic, gene expression and functional analysis to
      compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We
      showed that HIV-specific CD8 T cells in primary infection can be distinguished by
      their metabolic state, rate of proliferation, and susceptibility to apoptosis.
      HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-gamma but
      were more cytotoxic than their counterparts in chronic infection. Importantly, we
      showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T
      cells to secrete IL-2 on antigenic restimulation during primary infection were
      inversely correlated with the viral set-point. Altogether, these data suggest an
      altered metabolic state of HIV-specific CD8 T cells in primary infection
      resulting from hyperproliferation and stress induced signals, demonstrate the
      discordant function of HIV-specific CD8 T cells during early/acute infection, and
      highlight the importance of T-cell maintenance for viral control.

PMID- 22955927
TI  - Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to
      autologous CD4 T lymphocytes.
AB  - Dendritic cells (DCs) support only low levels of HIV-1 replication, but have been
      shown to transfer infectious viral particles highly efficiently to neighboring
      permissive CD4 T lymphocytes. This mode of cell-to-cell HIV-1 spread may be a
      predominant mode of infection and dissemination. In the present study, we
      analyzed the kinetics of fusion, replication, and the ability of HIV-1-specific
      Abs to inhibit HIV-1 transfer from immature DCs to autologous CD4 T lymphocytes.
      We found that neutralizing mAbs prevented HIV-1 transfer to CD4 T lymphocytes in
      trans and in cis, whereas nonneutralizing Abs did not. Neutralizing Abs also
      significantly decreased HIV-1 replication in DCs, even when added 2 hours after
      HIV-1 infection. Interestingly, a similar inhibition of HIV-1 replication in DCs
      was detected with some nonneutralizing Abs and was correlated with DC maturation.
      We suggest that the binding of HIV-1-specific Abs to FcgammaRs leads to HIV-1
      inhibition in DCs by triggering DC maturation. This efficient inhibition of HIV-1
      transfer by Abs highlights the importance of inducing HIV-specific Abs by
      vaccination directly at the mucosal portal of HIV-1 entry to prevent early
      dissemination after sexual transmission.

PMID- 22955928
TI  - HDAC6 controls the kinetics of platelet activation.
AB  - HDAC6, a major cytoplasmic deacetylase, is shown here to fine-tune the kinetics
      of platelet activation, a process that must be precisely regulated to ensure
      hemostasis after blood vessel injury while preventing pathologic thrombus
      formation. The discoid shape of resting platelets in the circulation is
      maintained by several highly acetylated microtubules organized in a marginal
      band. During platelet activation, microtubules undergo major reorganizations,
      which contribute to the shape change of activating platelets. We show that,
      during these activation-induced shape changes, a dramatic HDAC6-mediated tubulin
      deacetylation takes place, followed by microtubule reacetylation in spread
      platelets. In addition, although HDAC6-controlled tubulin deacetylation is not
      required for platelet activation, the capacity of HDAC6 to prevent tubulin
      hyperacetylation influences the speed of platelet spreading. These results are
      particularly important in view of HDAC6 inhibitors being currently used in
      clinical trials and represent the first example of cell signaling by lysine
      acetylation in platelet biology.

PMID- 22955930
TI  - In support of the BMRB.

PMID- 22955931
TI  - Getting ready to commit: ribosomes rehearse translation.

PMID- 22955932
TI  - Chromatin 'resetting' during transcription elongation: a central role for
      methylated H3K36.

PMID- 22955933
TI  - Pinpointing a puzzling polymerase.

PMID- 22955938
TI  - Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic
      patients: a combined EEG study using LORETA and Omega complexity : reversible
      alterations of brain activity in OSAS.
AB  - Effects of initiation of continuous positive airway pressure (CPAP) therapy on
      EEG background activity were investigated in patients with obstructive sleep
      apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of
      brain electrical activity caused by chronic hypoxia. Normal control group (N =
      14) was also examined. Two EEG examinations were done in each groups: at night
      and in the next morning. Global and regional (left vs. right, anterior vs.
      posterior) measures of spatial complexity (Omega complexity) were used to
      characterize the degree of spatial synchrony of EEG. Low resolution
      electromagnetic tomography (LORETA) was used to localize generators of EEG
      activity in separate frequency bands. Before CPAP-treatment, a significantly
      lower Omega complexity was found globally and over the right hemisphere. Due to
      CPAP-treatment, these significant differences vanished. Significantly decreased
      Omega complexity was found in the anterior region after treatment. LORETA showed
      a decreased activity in all of the beta bands after therapy in the right
      hippocampus, premotor and temporo-parietal cortex, and bilaterally in the
      precuneus, paracentral and posterior cingulate cortex. No significant changes
      were seen in control group. Comparing controls and patients before sleep, an
      increased alpha2 band activity was seen bilaterally in the precuneus, paracentral
      and posterior cingulate cortex, while in the morning an increased beta3 band
      activity in the left precentral and bilateral premotor cortex and a decreased
      delta band activity in the right temporo-parietal cortex and insula were
      observed. These findings indicate that effect of sleep on EEG background activity
      is different in OSAS patients and normal controls. In OSAS patients, significant
      changes lead to a more normal EEG after a night under CPAP-treatment.
      Compensatory alterations of brain electrical activity in regions associated with
      influencing sympathetic outflow, visuospatial abilities, long-term memory and
      motor performances caused by chronic hypoxia could be reversed by CPAP-therapy.

PMID- 22955939
TI  - Genetic and physical mapping of flowering time loci in canola (Brassica napus
      L.).
AB  - We identified quantitative trait loci (QTL) underlying variation for flowering
      time in a doubled haploid (DH) population of vernalisation-responsive canola
      (Brassica napus L.) cultivars Skipton and Ag-Spectrum and aligned them with
      physical map positions of predicted flowering genes from the Brassica rapa
      genome. Significant genetic variation in flowering time and response to
      vernalisation were observed among the DH lines from Skipton/Ag-Spectrum. A
      molecular linkage map was generated comprising 674 simple sequence repeat,
      sequence-related amplified polymorphism, sequence characterised amplified region,
      Diversity Array Technology, and candidate gene based markers loci. QTL analysis
      indicated that flowering time is a complex trait and is controlled by at least 20
      loci, localised on ten different chromosomes. These loci each accounted for
      between 2.4 and 28.6% of the total genotypic variation for first flowering and
      response to vernalisation. However, identification of consistent QTL was found to
      be dependant upon growing environments. We compared the locations of QTL with the
      physical positions of predicted flowering time genes located on the sequenced
      genome of B. rapa. Some QTL associated with flowering time on A02, A03, A07, and
      C06 may represent homologues of known flowering time genes in Arabidopsis;
      VERNALISATION INSENSITIVE 3, APETALA1, CAULIFLOWER, FLOWERING LOCUS C, FLOWERING
      LOCUS T, CURLY LEAF, SHORT VEGETATIVE PHASE, GA3 OXIDASE, and LEAFY.
      Identification of the chromosomal location and effect of the genes influencing
      flowering time may hasten the development of canola varieties having an optimal
      time for flowering in target environments such as for low rainfall areas, via
      marker-assisted selection.

PMID- 22955941
TI  - Multidimensional Adaptation in MAS Organizations.
AB  - Organization adaptation requires determining the consequences of applying changes
      not only in terms of the benefits provided but also measuring the adaptation
      costs as well as the impact that these changes have on all of the components of
      the organization. In this paper, we provide an approach for adaptation in
      multiagent systems based on a multidimensional transition deliberation mechanism
      (MTDM). This approach considers transitions in multiple dimensions and is aimed
      at obtaining the adaptation with the highest potential for improvement in utility
      based on the costs of adaptation. The approach provides an accurate measurement
      of the impact of the adaptation since it determines the organization that is to
      be transitioned to as well as the changes required to carry out this transition.
      We show an example of adaptation in a service provider network environment in
      order to demonstrate that the measurement of the adaptation consequences taken by
      the MTDM improves the organization performance more than the other approaches. 

PMID- 22955940
TI  - Local inflammation is associated with aortic thrombus formation in abdominal
      aortic aneurysms. Relationship to clinical risk factors.
AB  - Intraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated
      with adverse clinical prognosis. Interplay between coagulation and inflammation,
      characterised by leukocyte infiltration and cytokine production, has been
      implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by
      flow cytometry in AAA thrombi from 27 patients undergoing surgical repair.
      Luminal parts of thrombi were leukocyte-rich, while abluminal segments showed low
      leukocyte content. CD66b+ granulocytes were the most prevalent, but their content
      was similar to blood. Monocytes (CD14+) and T cells (CD3+) were also abundant,
      while content of B lymphocytes (CD19+) and NK cells (CD56+CD16+) were low.
      Thrombi showed comparable content of CD14highCD16- monocytes and lower
      CD14highCD16+ and CD14dimCD16+, than blood. Monocytes were activated with high
      CD11b, CD11c and HLA-DR expression. Total T cell content was decreased in AAA
      thrombus compared to peripheral blood but CD8 and CD3+CD4-CD8- (double negative T
      cell) contents were increased in thrombi. CD4+ cells were lower but highly
      activated (high CD69, CD25 and HLA-DR). No differences in T regulatory
      (CD4+CD25+FoxP3+) cell or pro-atherogenic CD4+CD28null lymphocyte content were
      observed between thrombi and blood. Thrombus T cells expressed high levels of
      CCR5 receptor for chemokine RANTES, commonly released from activated platelets.
      Leukocyte or T cell content in thrombi was not correlated with aneurysm size.
      However, CD3+ content was significantly associated with smoking in multivariate
      analysis taking into account major risk factors for atherosclerosis. In
      conclusion, intraluminal AAA thrombi are highly inflamed, predominantly with
      granulocytes, CD14highCD16- monocytes and activated T lymphocytes. Smoking is
      associated with T cell infiltration in AAA intraluminal thrombi.

PMID- 22955942
TI  - k-t BLAST and SENSE accelerated time-resolved three-dimensional phase contrast
      MRI in an intracranial aneurysm.
AB  - OBJECTIVE: The objective of this study was to investigate the performance of k-t
      BLAST (Broad-use Linear Acquisition Speed-up Technique) accelerated time-resolved
      3D PC-MRI compared to SENSE (SENSitivity Encoding) acceleration in an in vitro
      and in vivo intracranial aneurysm. MATERIALS AND METHODS: Non-accelerated, SENSE
      and k-t BLAST accelerated time-resolved 3D PC-MRI measurements were performed in
      vivo and in vitro. We analysed the consequences of various temporal resolutions
      in vitro. RESULTS: Both in vitro and in vivo measurements showed that the main
      effect of k-t BLAST was underestimation of velocity during systole. In the
      phantom, temporal blurring decreased with increasing temporal resolution.
      Quantification of the differences between the non-accelerated and accelerated
      measurements confirmed that in systole SENSE performed better than k-t BLAST in
      terms of mean velocity magnitude. In both in vitro and in vivo measurements, k-t
      BLAST had higher SNR compared to SENSE. Qualitative comparison between
      measurements showed good similarity. CONCLUSION: Comparison with SENSE revealed
      temporal blurring effects in k-t BLAST accelerated measurements.

PMID- 22955943
TI  - Evaluation of an attenuation correction method for PET/MR imaging of the head
      based on substitute CT images.
AB  - OBJECT: The aim of this study was to evaluate MR-based attenuation correction of
      PET emission data of the head, based on a previously described technique that
      calculates substitute CT (sCT) images from a set of MR images. MATERIALS AND
      METHODS: Images from eight patients, examined with (18)F-FLT PET/CT and MRI, were
      included. sCT images were calculated and co-registered to the corresponding CT
      images, and transferred to the PET/CT scanner for reconstruction. The new
      reconstructions were then compared with the originals. The effect of replacing
      bone with soft tissue in the sCT-images was also evaluated. RESULTS: The average
      relative difference between the sCT-corrected PET images and the CT-corrected PET
      images was 1.6% for the head and 1.9% for the brain. The average standard
      deviations of the relative differences within the head were relatively high, at
      13.2%, primarily because of large differences in the nasal septa region. For the
      brain, the average standard deviation was lower, 4.1%. The global average
      difference in the head when replacing bone with soft tissue was 11%. CONCLUSION:
      The method presented here has a high rate of accuracy, but high-precision
      quantitative imaging of the nasal septa region is not possible at the moment.

PMID- 22955944
TI  - A novel cellular stress response characterised by a rapid reorganisation of
      membranes of the endoplasmic reticulum.
AB  - Canonical endoplasmic reticulum (ER) stress, which occurs in many physiological
      and disease processes, results in activation of the unfolded protein response
      (UPR). We now describe a new, evolutionarily conserved cellular stress response
      characterised by a striking, but reversible, reorganisation of ER membranes that
      occurs independently of the UPR, resulting in impaired ER transport and function.
      This reorganisation is characterised by a dramatic redistribution and clustering
      of ER membrane proteins. ER membrane aggregation is regulated, in part, by anti
      apoptotic BCL-2 family members, particularly MCL-1. Using connectivity mapping,
      we report the widespread occurrence of this stress response by identifying
      several structurally diverse chemicals from different pharmacological classes,
      including antihistamines, antimalarials and antipsychotics, which induce ER
      membrane reorganisation. Furthermore, we demonstrate the potential of ER membrane
      aggregation to result in pathological consequences, such as the long-QT syndrome,
      a cardiac arrhythmic abnormality, arising because of a novel trafficking defect
      of the human ether-a-go-go-related channel protein from the ER to the plasma
      membrane. Thus, ER membrane reorganisation is a feature of a new cellular stress
      pathway, clearly distinct from the UPR, with important consequences affecting the
      normal functioning of the ER.

PMID- 22955945
TI  - Cell surface-expressed phosphatidylserine as therapeutic target to enhance
      phagocytosis of apoptotic cells.
AB  - Impaired efferocytosis has been shown to be associated with, and even to
      contribute to progression of, chronic inflammatory diseases such as
      atherosclerosis. Enhancing efferocytosis has been proposed as strategy to treat
      diseases involving inflammation. Here we present the strategy to increase 'eat
      me' signals on the surface of apoptotic cells by targeting cell surface-expressed
      phosphatidylserine (PS) with a variant of annexin A5 (Arg-Gly-Asp-annexin A5, RGD
      anxA5) that has gained the function to interact with alpha(v)beta(3) receptors of
      the phagocyte. We describe design and characterization of RGD-anxA5 and show that
      introduction of RGD transforms anxA5 from an inhibitor into a stimulator of
      efferocytosis. RGD-anxA5 enhances engulfment of apoptotic cells by phorbol-12
      myristate-13-acetate-stimulated THP-1 (human acute monocytic leukemia cell line)
      cells in vitro and resident peritoneal mouse macrophages in vivo. In addition,
      RGD-anxA5 augments secretion of interleukin-10 during efferocytosis in vivo,
      thereby possibly adding to an anti-inflammatory environment. We conclude that
      targeting cell surface-expressed PS is an attractive strategy for treatment of
      inflammatory diseases and that the rationally designed RGD-anxA5 is a promising
      therapeutic agent.

PMID- 22955946
TI  - Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an
      activator of caspase-mediated apoptosis.
AB  - Little is known about the cellular mechanisms modulating the shift in balance
      from a state of survival to cell death by caspase-mediated apoptosis in response
      to a lethal stress. Here we show that the RNA-binding protein HuR has an
      important function in mediating this switch. During caspase-mediated apoptosis,
      HuR is cleaved to generate two cleavage products (CPs). Our data demonstrate that
      the cleavage of HuR switches its function from being a prosurvival factor under
      normal conditions to becoming a promoter of apoptosis in response to a lethal
      stress. In the absence of an apoptotic stimuli, HuR associates with and promotes
      the expression of caspase-9 and prothymosin alpha (ProT) mRNAs, and pro- and
      antiapoptotic factors, respectively, both of which have been characterized as
      important players in determining cell fate. During the early steps of caspase
      mediated apoptosis, however, the level of caspase-9 protein increases, while ProT
      remains unchanged. Under these conditions, the two HuR-CPs selectively bind to
      and stabilize caspase-9 mRNA, but do not bind to ProT. Hence, taken together, our
      data show that by maintaining a threshold of expression of proapoptotic factors
      such as caspase-9 in response to a lethal stress, the HuR-CPs help a cell to
      switch from resisting death to undergoing apoptosis.

PMID- 22955947
TI  - Suppressor of cytokine signaling 6 (SOCS6) promotes mitochondrial fission via
      regulating DRP1 translocation.
AB  - Mitochondria are highly motile organelles that constantly undergo fission and
      fusion. Impairment of mitochondrial dynamics is associated with mitochondrial
      dysfunction and is frequently linked to the pathogenesis of neurodegenerative
      diseases and cancer. We have previously shown that biallelic inactivation of the
      suppressor of cytokine signaling 6 (SOCS6) gene is a frequent event in human
      gastric cancer. In this study, we recapitulated the event of SOCS6 loss using a
      Lentivirus-based knockdown approach, and demonstrated the linkage between SOCS6
      depletion and the suppression of programmed cell death. SOCS6 promotes intrinsic
      apoptosis, with increased Bax conformational change, mitochondrial targeting, and
      oligomerization. Most importantly, SOCS6 is targeted to mitochondria and induces
      mitochondrial fragmentation mediated through an increase in DRP1 fission
      activity. Here, we show that SOCS6 forms complex with DRP1 and the mitochondrial
      phosphatase PGAM5, attenuates DRP1 phosphorylation, and promotes DRP1
      mitochondrial translocation. Based on mutation analyses, SOCS6-mediated apoptosis
      is tightly coupled to its ability to induce mitochondrial fission. This study
      demonstrates an important role for SOCS6 in modulating mitochondrial dynamics and
      apoptosis.

PMID- 22955949
TI  - Caffeine drinking, cigarette smoking, and dopaminergic replacement therapy dose
      in Parkinson's disease.
AB  - The objective of this study is to assess the effect of smoking and caffeine
      intake in the dosage of dopaminergic replacement therapy. Patients were recruited
      from the movement disorders clinic of the National Institute of Neurology and
      Neurosurgery in Mexico City. An interviewer-administered structured questionnaire
      was given to all subjects regarding their smoking and caffeine drinking habits.
      Dopaminergic replacement therapy information was collected and levodopa, dopamine
      agonists, and levodopa equivalent daily doses were calculated. 146 Parkinson's
      disease patients (50 % female) were included. All patients were on
      antiparkinsonian treatment, with a mean levodopa equivalent daily dose (LEDD) of
      550.2 +/- 408. Patients were stratified according to smoking and caffeine
      drinking status. 104 (71.2 %) of the patients were "never smokers", 33 (22.6 %)
      were "former smokers" and 9 (6.2 %) were "current smokers". 40 (27.4 %) patients
      reported no history of caffeine intake, 36 (24.7 %) were former consumers and 70
      (47.9 %) were current caffeine drinkers. No association between LEDD and smoking
      or caffeine intake was found. A weak positive correlation (r = 0.22, p < 0.04)
      was found between the daily dose of pramipexole and the daily intake of caffeine.
      LEDD, levodopa daily dose and dopamine agonist daily dose were not related to
      smoking or caffeine intake status. We found a weak correlation between caffeine
      daily intake and pramipexole dose. Further prospective exploration is needed to
      address the interaction of concomitant A2A antagonism induced by caffeine intake
      and dopaminergic replacement therapy.

PMID- 22955948
TI  - IKK-beta mediates hydrogen peroxide induced cell death through p85 S6K1.
AB  - The IkappaB kinase (IKK)/NF-kappaB pathway has been shown to be a major regulator
      in cell survival. However, the mechanisms through which IKK mediates cell death
      are not clear. In this study, we showed that IKK-beta contributed to hydrogen
      peroxide (H(2)O(2))-induced cell death independent of the NF-kappaB pathway. Our
      results demonstrated that the pro-death function of IKK-beta under oxidative
      stress was mediated by p85 S6K1 (S6 kinase 1), but not p70 S6K1 through a
      rapamycin-insensitive and mammalian target of rapamycin complex 1 kinase
      independent mechanism. We found that IKK-beta associated with p85, but not p70
      S6K1, which was required for H(2)O(2)-induced activation of p85 S6K1. IKK-beta
      and p85 S6K1 contributed to H(2)O(2)-induced phosphorylation of Mdm2 (S166) and
      p53 accumulation. p85 S6K1 is critical for IKK-beta-mediated cell death. Thus,
      these findings established a novel oxidative stress-responsive pathway that
      involves IKK-beta, p85 S6K1 and Mdm2, which is response for H(2)O(2)-induced cell
      death. Our results have important implications for IKK-beta and p85 S6K1 as
      potential targets for the prevention of diseases involved in oxidative stress
      induced aberrant cell death.

PMID- 22955951
TI  - A survey of surgical capacity in rural southern Nigeria: opportunities for
      change.
AB  - BACKGROUND: Despite growing recognition of the massive surgical burden of
      disease, unmet need, and disparities in access to care in many African countries,
      little is known about their capacity to deliver surgical, obstetric, emergency,
      and anesthetic care, particularly in the rural areas where up to 50% of the
      population lives. This study aimed to quantify the surgical capacity of select
      healthcare facilities in rural southern Nigeria in five key areas: Workforce,
      Infrastructure, Skill, Equipment, and Supplies. METHODS: We assessed the surgical
      capacity of 41 private, rural hospitals in southern Nigeria using the Personnel,
      Infrastructure, Procedures, Equipment, and Supplies survey tool developed by
      Surgeons OverSeas. The survey was administered to surgical practitioners during
      their annual conference in November 2011. RESULTS: Among the 41 hospitals
      surveyed, general practitioners (52.1%) constituted most of the surgical
      workforce. Only one anesthesiologist was available in 16 secondary hospitals.
      Although most of the primary and secondary hospitals had running water (82.3%), a
      designated emergency room (80.5%), and medical records (95.9%), only 50.3% of all
      hospitals had electricity through the power grid. Also, only 37.5% of all
      facilities had a blood bank and 43.8% had an X-ray machine. Common surgical
      procedures were done by most of the facilities; however, cricothyroidotomy,
      clubfoot repair, and obstetric fistula repair were scarcely done. Less than half
      of the facilities provided general anesthesia, only 20% have an anesthesia
      machine, and 44.5% have a pulse oximeter. CONCLUSION: Severe shortages in key
      areas should motivate stakeholders to devote more effort and resources to
      strengthening surgical capacity in rural southern Nigeria.

PMID- 22955950
TI  - The 1-2-3 approach to abdominal packing.
AB  - BACKGROUND: Abdominal packing (AP) in damage-control laparotomy (DCL) is a
      lifesaving technique that controls coagulopathic hemorrhage in severely injured
      trauma patients. However, the impact of the duration of AP on the incidence of re
      bleeding and on intra-abdominal infections in penetrating abdominal trauma is not
      clear. The objective of the present study was to evaluate the complications
      related to the duration of AP and to determine the optimal time for AP removal.
      METHODS: Prospectively collected/retrospectively analyzed data at an urban level
      I trauma center from January 2003 to December 2010 were used as the basis for
      this study. Inclusion criteria were adults (>=18 years old) with penetrating
      abdominal trauma, who had survived both the initial DCL procedure and their first
      re-laparotomy. All initial DCL patients included in the study underwent abdominal
      packing for coagulopathic hemorrhage control. The outcome measures of this study
      were re-bleeding after packing removal, intra-abdominal infection, and 30-day
      cumulative mortality. We considered time after packing as an independent
      variable. This was defined as the total amount of time (in days) that the packs
      were left in the patient's abdomen. Patients were grouped according to the
      duration in days of their AP in <1, 1-2, 2-3, and >3 days. RESULTS: Of 503
      patients with penetrating abdominal trauma, 121 underwent DCL and AP. The mean
      age was 30.1+/- 11.5 years, and the male to female ratio was 9:1. The mean Acute
      Physiology and Chronic Health Evaluation (APACHE II) score was 17.6+/-7.2. The
      mean Injury Severity Score (ISS) score was 24.9+/-9.1. The right upper quadrant
      was packed in 39 (32.2%) patients, retroperitoneum in 70 (57.8%), pelvis in 13
      (10.7%), and left upper quadrant in 9 (7.4%). Fifty-one patients (42.1%) had
      associated colon injuries and 58 (47.9%) had small bowel injuries. Twenty-six
      patients (21.5%) had AP<1 day, 42 patients (34.7%) had AP between 1 and 2 days,
      35 patients (28.9%) had AP between 2 and 3 days, and 18 patients (14.8%) had AP>3
      days. The re-bleeding rate in patients packed for 1-2 days compared to those
      packed for <1 day was a third lower, 14.3%, (95% confidence interval [95% CI]:
      8.06, 20.5) versus 38.5% (95% CI: 25.4, 51.5). Conversely, an increasing trend
      toward intra-abdominal infection occurred as time after packing increased. The
      infection rate tripled from 16.7% (95% CI: 6.6, 26.7) to 44.4% (95% CI: 31.03,
      57.7) when comparing 1-2 days versus >3 days. Overall mortality was 16.5%. Of
      these deaths, 8.26% were attributable to re-bleeding, and 13.2% to intra
      abdominal infection. Deaths secondary to re-bleeding seemed to decrease with time
      of AP, whereas intra-abdominal infection deaths increased with time of AP (Chi
      square for trend p value=0.04). CONCLUSIONS: The present study suggests that AP
      used in the setting of DCL for coagulopathic hemorrhage control should not be
      removed prior to the first postoperative day because of the increased risk of re
      bleeding. The ideal length of AP is 2-3 days, and AP left in longer than 3 days
      is associated with a significantly increased risk of infectious complications.

PMID- 22955952
TI  - Can plasma bile salt, triglycerides, and apoA-V levels predict liver
      regeneration?
AB  - BACKGROUND: Preoperative portal vein embolization (PVE) is used to increase the
      future remnant liver (FRL) in patients requiring extensive liver resection.
      Computed tomography (CT) volumetry, performed not earlier than 3-6 weeks after
      PVE, is commonly employed to assess hypertrophy of the FRL following PVE. Early
      parameters to predict effective hypertrophy are therefore desirable. The aim of
      the present study was to assess plasma bile salt levels, triglycerides (TG), and
      apoA-V in the prediction of the hypertrophy response during liver regeneration.
      METHODS: Serum bile salt, TG, and apoA-V levels were determined in 20 patients
      with colorectal metastases before PVE, and 5 h, 1, and 21 days after PVE, as well
      as prior to and after (day 1-7, and day 21) subsequent liver resection. These
      parameters were correlated with liver volume as measured by CT volumetry (%FRL
      V), and liver function was determined by technetium-labeled mebrofenin
      hepatobiliary scintigraphy using single photon emission computed tomography.
      RESULTS: Triglyceride levels at baseline correlate with volume increase of the
      future remnant liver (FRL-V) post-PVE. Also, bile salts and TG 5 h after PVE
      positively correlated with the increase in FRL volume (r=0.672, p=0.024; r=0.620,
      p=0.042, resp.) and liver function after 3 weeks (for bile salts r=0.640,
      p=0.046). Following liver surgery, TG levels at 5 h and 1 day after resection
      were associated with liver remnant volume after 3 months (r=0.921, p=0.026 and
      r=0.981, p=0.019, resp). Plasma apoA-V was increased during liver regeneration.
      CONCLUSIONS: Bile salt and TG levels at 5 h after PVE/resection are significant
      early predictors of liver volume and functional increase. It is suggested that
      these parameters can be used for early timing of volume assessment and resection
      after PVE.

PMID- 22955953
TI  - Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography
      in predicting the pathologic response to preoperative chemoradiation therapy in
      patients with resectable T3 pancreatic cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate whether (18)F
      fluorodeoxyglucose positron emission tomography in combination with computed
      tomography (FDG-PET/CT) could correctly predict the pathologic response to
      preoperative chemoradiation therapy (CRT) for resectable pancreatic cancer.
      METHODS: Each of the 40 patients underwent FDG-PET/CT before and after
      preoperative CRT. The maximum standard uptake value (SUV) was measured for the
      primary tumor before and after preoperative CRT, defined as pre-CRT SUV and post
      CRT SUV, respectively. The proportional alteration of the SUV decline (regression
      index) between post-CRT SUV and pre-CRT SUV was also calculated. These three
      indicators were associated with the pathologic response. RESULTS: Patients were
      classified as 21 responders and 19 nonresponders according to the histologic
      features. A pre-CRT SUV >= 4.7 was seen in 15 (71 %) of 21 responders and in 6
      (32 %) of 19 nonresponders (p = 0.03). A regression index >= 0.46 was seen in 15
      (71 %) responders and 5 (26 %) nonresponders (p = 0.01). CONCLUSIONS: A better
      pathological response can be expected for pancreatic cancer patients who have a
      high regression index (>= 0.46) and a high pre-CRT SUV (>= 4.7). The SUV
      measurement using FDG-PET/CT is a useful tool for predicting the pathologic
      response to preoperative CRT.

PMID- 22955954
TI  - Increased detection of non-recurrent inferior laryngeal nerve (NRLN) during
      thyroid surgery using systematic intraoperative neuromonitoring (IONM).
AB  - BACKGROUND: Non-recurrent inferior laryngeal nerve (NRLN) is a rare anatomical
      variant with a reported incidence of 0.6-1.3 %. It carries a higher risk of palsy
      during thyroid surgery. Its detection is mandatory in order to avoid such
      complication. METHODS: Systematic intraoperative neuromonitoring (IONM) was
      carried out for 806 consecutive nerve at risk (NAR) patients in two centers
      (Lille and Varese). In 402 patients surgery to the right side was performed with
      IONM. The IONM of the inferior laryngeal nerve (ILN) was conducted as recommended
      by international guidelines (V1/R1/V2/R2). RESULTS: A NRLN was detected in 11 of
      402 NAR (2.7 %). In the first center (Lille) the incidence of NRLN was 6.0 %
      (7/117). No loss of signal (LOS) was reported in this group of patients.
      Postoperative laryngoscopy was normal in all patients with NRLN. CONCLUSIONS: The
      true incidence of NRLN may be higher than expected. Neurophysiology helps the
      surgeon to better understand the anatomy and function of nervous structures.
      Intraoperative neuromonitoring is a useful tool that should be systematically
      implemented in thyroid surgery to better understand the anatomy and physiology of
      the inferior laryngeal nerve. Its use may allow the surgeon to decrease the
      incidence of nerve palsy especially in case of NRLN. The IONM adjunct does not
      add significantly to the costs for thyroid surgery.

PMID- 22955955
TI  - The attitude and perceptions of work-life balance: a comparison among women
      surgeons in Japan, USA, and Hong Kong China.
AB  - BACKGROUND: The objective of the present study was to explore how women surgeons
      manage their work-life balance in three environmental and cultural settings.
      METHOD: Members of the Japan Association of Women Surgeons (JAWS), the United
      States of America (US) based Association of Women Surgeons (AWS), and the Women's
      Chapter of the College of Surgeons of Hong Kong (WCHK) were surveyed. RESULTS:
      Among 822 women surgeons contacted, 252 responded (response rate 31.8 %; 55.5 %
      JAWS, 28.2 % AWS, and 25.3 % WCHK). Japanese women surgeons think that work is
      the number one priority, whereas US and Hong Kong China (HK) respondents think
      the number one priority is home life. Work satisfaction level was generally high
      among women surgeons in all countries; however, 19 % of US surgeons are somewhat
      dissatisfied with their work and 76.1 % think that men are treated more favorably
      than women at work. Whereas 51.6 % of Japanese women surgeons think that men are
      treated more favorably than women at home, at the same time they placed more
      importance on the role of women in the family. More than half of Japanese women
      surgeons are "uncertain" about their career path in the future, whereas 55.2/87.1
      % of US/HK respondents are optimistic. All surgeons recommended expanding support
      for child rearing or nursing care during work hours, promoting a flexible work
      schedule and changing some of the older conventional ideas about gender role.
      CONCLUSIONS: It is essential to address women surgeons' concerns to enable them
      to have a clearer vision and a challenging career, and to be more certain about
      their personal and professional goals.

PMID- 22955956
TI  - The positive influence of boron-doped graphene for its supported Au clusters:
      enhancement of SERS and oxygen molecule adsorption.
AB  - The interactions between Au clusters and graphene sheets with and without doping
      have been studied systematically. It is found that B-doped graphene is a good
      support for Au clusters, not only because of the charge transfer from the
      graphene sheet to its supported Au clusters, but also due to its stronger
      interaction at the interface resulting from the doped B atom, which will
      facilitate more electrons being transferred to the upper surface of the Au
      cluster. This is good for surface-enhanced Raman scattering (SERS) and molecule
      oxygen adsorption, beneficial to the material preparation and apparatus design
      for high active SERS substrates and nano-catalysts.

PMID- 22955957
TI  - Efficacy and safety of higher doses of botulinum toxin type A NT 201 free from
      complexing proteins in the upper and lower limb spasticity after stroke.
AB  - Botulinum toxin type A (BTX-A) represents the gold standard therapy for focal
      spasticity after stroke, with low prevalence of complications, reversibility, and
      efficacy in reducing spastic hypertonia. Current guidelines suggest the
      employment of a dosage up to 600 units (U) of BTX-A to treat spasticity after
      stroke, to avoid important adverse effects and the development of antibodies
      against the neurotoxin. In recent years, NT 201, a new BTX-A free of complexing
      proteins, has been used for treating several movement disorders, showing safety
      and efficacy in upper limb spasticity. In a prospective, non-randomized, open
      label study, we studied the efficacy and safety of higher doses of BTX-A NT 201
      (up to 840 U) in 25 consecutive patients with upper and lower limb spasticity
      after stroke, evaluated at 30 and 90 days after injections. Before and after the
      treatment, the grade of spasticity, the disability, and spasticity-related pain
      were extensively measured. After 30 days of follow-up, a great reduction of
      spasticity and pain with improvement of disability was observed. The effects were
      still present at 90 days of follow-up. No major adverse events were observed.
      Higher doses of BTX-A NT 201 appeared to be safe and efficacious in patients with
      upper and lower limb spasticity after stroke. However, further investigations are
      needed to determine its reproducibility in larger case series or randomized
      clinical trials and to observe the absence of antibodies against the neurotoxin
      also after repeated injections.

PMID- 22955958
TI  - Appearance of neural stem cells around the damaged area following traumatic brain
      injury in aged rats.
AB  - We have previously reported free radical production after traumatic brain injury
      (TBI), which induces neural stem cell (NSC) degeneration and death. However, the
      effects of aging on NSC proliferation around the damaged area following TBI have
      not been investigated. Therefore, in this study, we used 10-week (young group)
      and 24-month-old (aged group) rat TBI models to investigate the effects of aging
      on NSC proliferation around damaged tissue using immunohistochemical and ex vivo
      techniques. Young and aged rats received TBI. At 1, 3 and 7 days after TBI,
      immunohistochemical and lipid peroxidation studies were performed.
      Immunohistochemistry revealed that the number of nestin-positive cells around the
      damaged area after TBI in the aged group decreased significantly when compared
      with those in the young group (P < 0.01). However, the number of 8-hydroxy-2'
      deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive
      cells and the level of peroxidation around the damaged area after TBI
      significantly increased in the aged group, compared with those in the young group
      (P < 0.01). Furthermore, almost all ssDNA-positive cells in young and aged groups
      co-localized with NeuN and nestin staining. Ex vivo studies revealed that
      neurospheres, which differentiated into neurons and glia in culture, could only
      be isolated from injured brain tissue in young and aged groups at 3 days after
      TBI. These results indicate that, although there were fewer NSCs that have the
      potential to differentiate into neurons and glia, these NSCs escaped free radical
      induced degeneration around the damaged area after TBI in the aged rat brain.

PMID- 22955959
TI  - Design and evaluation of NEUROBike: a neurorehabilitative platform for bedridden
      post-stroke patients.
AB  - Over the past decades, a large number of robotic platforms have been developed
      which provide rehabilitative treatments aimed at recovering walking abilities in
      post-stroke patients. Unfortunately, they do not significantly influence
      patients' performance after three months from the accident. One of the main
      reasons underlying this result seems to be related to the time of intervention.
      Specifically, although experimental evidences suggest that early (i.e., first
      days after the injury) and intense neuro-rehabilitative treatments can
      significantly favor the functional recovery of post-stroke patients, robots
      require patients to be verticalized. Consequently, this does not allow them to be
      treated immediately after the trauma. This paper introduces a new robotic
      platform, named NEUROBike, designed to provide neuro-rehabilitative treatments to
      bedridden patients. It was designed to provide an early and well-addressed
      rehabilitation therapy, in terms of kinesiology, efforts, and fatigue, accounting
      for exercises functionally related to daily motor tasks. For this purpose,
      kinematic models of leg-joint angular excursions during both walking and sit-to
      stand were developed and implemented in control algorithms leading both passive
      and active exercises. Finally, a set of pilot tests was carried out to evaluate
      the performance of the robotic platform on healthy subjects.

PMID- 22955960
TI  - Grading of uterine cervical cancer by using the ADC difference value and its
      correlation with microvascular density and vascular endothelial growth factor.
AB  - OBJECTIVE: To investigate the application value of the ADC(difference) value in
      evaluating the pathological grade of uterine cervical cancer and to analyse the
      correlations among microvascular density (MVD), vascular endothelial growth
      factor (VEGF) expression and maximum ADC(difference) value. METHODS: Fifty-six
      patients with uterine cervical cancer were included in this prospective study.
      All underwent conventional MRI and DWI. MVD and VEGF were evaluated by
      immunohistochemical staining with anti-CD34 and anti-VEGF, respectively. RESULTS:
      Maximum ADC(difference) value and MVD count showed statistical differences among
      different pathological grades (P < 0.001, P < 0.001). There was a significant
      positive linear correlation between the maximum ADC(difference) value and
      pathological tumour grade (P < 0.001), and also between MVD count and
      pathological tumour grade (P < 0.001). No significant differences were found
      between the level of VEGF expression and pathological tumour grade (P = 0.222).
      The maximum ADC(difference) value correlated positively with both the MVD count
      and the level of VEGF expression (P < 0.001, P < 0.001). CONCLUSIONS:
      Quantitative analysis of maximum ADC(difference) value of uterine cervical cancer
      may represent the grade of tumour differentiation and provide valuable
      information on tumour microcirculation and perfusion, thus allowing a promising
      new method of non-invasively assessing the pathological grade, which could serve
      as a substitution for assessing tumour angiogenesis.

PMID- 22955961
TI  - Triple hydrogen bonding in a circular arrangement: ab initio, DFT and first
      principles MD studies of tris-hydroxyaryl enamines.
AB  - First-principles Car-Parrinello molecular dynamics, ab initio (MP2) and density
      functional schemes have been used to explore the tautomeric equilibrium in three
      tris(amino(R)methylidene)cyclohexane-1,3,5-triones (R = hydrogen, methyl or
      phenyl group). The dynamic nature of the cyclic hydrogen bonding has been studied
      by the first-principles MD method. The comparison of the results obtained by
      aforesaid methods has been accomplished on the basis of calculations of
      structural and spectroscopic characteristics of the compounds. The conformational
      analysis of the studied compounds has been carried out at the MP2/6-31+G(d,p) and
      B3LYP/6-31+G(d,p) levels of theory. The influence of steric and electronic
      effects on the cyclic hydrogen bonding has been analysed. The extent of the
      proton delocalization has been modified by the substituents according to the
      sequence: hydrogen < phenyl < methyl. This fact is verified by the spectroscopic
      and structural data as well as the energy potential curve. A prevalence of the
      keto-enamine tautomeric form has been observed in the static ab initio and DFT
      models, and confirmed by the first-principles MD.

PMID- 22955962
TI  - Total substitution of fish oil by vegetable oils in Senegalese sole (Solea
      senegalensis) diets: effects on fish performance, biochemical composition, and
      expression of some glucocorticoid receptor-related genes.
AB  - To study the substitution of fish oil by vegetable oils in fish diets, juveniles
      Senegalese sole (Solea senegalensis) were fed diets (56 % crude protein, 12 %
      crude lipid) containing either linseed (100LO) or soybean (100SO) oils in
      comparison with a 100 % fish oil-based diet (100FO) for 90 days. Samples of
      muscle, liver, and intestine were collected for biochemical analysis and for
      glucocorticoid receptor-related genes, including GR1 and GR2, and the associated
      heat shock proteins HSP70, HSP90AA, and HSP90AB. Besides, basal levels of plasma
      cortisol were also determined. After the feeding period, a stress test,
      consisting on 5 min of net chasing, was applied to a selected population of each
      dietary group. Total replacement of fish oil by vegetable oils did not induced
      changes in fish growth and performance, but affected fatty acid profile of
      muscle, liver, and intestine, reflecting those tissues the characteristic fatty
      acids of each type of dietary oil. A tendency to conserve the ARA/EPA ratio could
      be observed in the different tissues, despite of the level of these fatty acids
      in diet. Chasing stress induced an increase of muscle GR1 and a reduction in
      intestinal GR2 relative expressions at any of the experimental diets assayed. In
      liver, chasing stress induced an increase in both GR1 and GR2 gene expression in
      fish fed fish oil diets. Similarly, chasing stress induced an increase of muscle
      HSP70 and decrease of HSP90AB in liver at any of the experimental diet assayed.
      Besides, vegetable oils decreased the expression of HSP70 in intestine, being the
      relative expression of liver HSP90AA increased by the inclusion of linseed oil in
      the diet, at any of the experimental conditions assayed.

PMID- 22955963
TI  - Identification and expression analysis of a CC chemokine from cobia (Rachycentron
      canadum).
AB  - Chemokines are small, secreted cytokine peptides known principally for their
      ability to induce migration and activation of leukocyte populations and regulate
      the immune response mechanisms. The cobia (Rachycentron canadum), a marine
      finfish species, has a great potential for net cage aquaculture in the South
      China Sea. We isolated and characterized a CC chemokine cDNA from cobia
      designated RcCC2. Its cDNA is 783 bp in length and encodes a putative protein of
      110 amino acids. Homology and phylogenetic analysis revealed that the RcCC2 gene,
      which contains four conserved cysteine residues, shares a high degree of
      similarity with other known CC chemokine sequences and is closest to the CCL19/21
      clade. The mRNA of RcCC2 is expressed constitutively in all tested tissues,
      including gill, liver, muscle, spleen, kidney, head kidney, skin, brain, stomach,
      intestine and heart, but not blood, with the highest level of expression in gill
      and liver. The reverse transcription quantitative polymerase chain reaction was
      used to examine the expression of the RcCC2 gene in immune-related tissues,
      including head kidney, spleen and liver, following intraperitoneal injection of
      the viral mimic polyriboinosinic polyribocytidylic acid, formalin-killed Vibrio
      carchariae (bacterial vaccine) and phosphate-buffered saline as a control. RcCC2
      gene expression was up-regulated differentially in head kidney, spleen and liver
      during 12 h after challenge. These results indicate that the RcCC2 gene is
      inducible and is involved in immune responses, suggesting RcCC2 has an important
      role in the early stage of viral and bacterial infections.

PMID- 22955964
TI  - On the fabric of the human body.

PMID- 22955966
TI  - Enhancing the production of tropane alkaloids in transgenic Anisodus acutangulus
      hairy root cultures by over-expressing tropinone reductase I and hyoscyamine
      6beta-hydroxylase.
AB  - Tropane alkaloids (TA) including hyoscyamine, anisodamine, scopolamine and
      anisodine, are used medicinally as anticholinergic agents with increasing market
      demand, so it is very important to improve TA production by metabolic engineering
      strategy. Here, we report the simultaneous introduction of genes encoding the
      branch-controlling enzyme tropinone reductase I (TRI, EU424321) and the
      downstream rate-limiting enzyme hyoscyamine-6beta-hydroxylase (H6H, EF187826)
      involved in TA biosynthesis into Anisodus acutangulus hairy roots by
      Agrobacterium-mediated gene transfer technology. Transgenic hairy root lines
      expressing both TRI and H6H (TH lines) produced significantly higher (P < 0.05)
      levels of TA compared with the control and single gene transformed lines (T or H
      lines). The best double gene transformed line (TH53) produced 4.293 mg g(-1) TA,
      which was about 4.49-fold higher than that of the control lines (0.96 mg g(-1)).
      As far as it is known, this is the first report on simultaneous introduction of
      TRI and H6H genes into TA-producing plant by biotechnological approaches.
      Besides, the content of anisodine was also greatly improved in A. acutangulus by
      over-expression of AaTRI and AaH6H genes. The average content of anisodine in TH
      lines was 0.984 mg g(-1) dw, about 18.57-fold of BC lines (0.053 mg g(-1) dw).
      This is the first time that this phenomenon has been found in TA-producing
      plants.

PMID- 22955967
TI  - Identification of hierarchical and overlapping functional modules in PPI
      networks.
AB  - Various evidences have demonstrated that functional modules are overlapping and
      hierarchically organized in protein-protein interaction (PPI) networks. Up to
      now, few methods are able to identify both overlapping and hierarchical
      functional modules in PPI networks. In this paper, a new hierarchical clustering
      algorithm, called OH-PIN, is proposed based on the overlapping   M_clusters,  
      lambda-module, and a new concept of clustering coefficient between two clusters.
      By recursively merging two clusters with the maximum clustering coefficient, OH
      PIN finally assembles all  M_clusters  into  lambda -modules. Since  M_clusters
      are overlapping,  lambda -modules based on them are also overlapping. Thus, OH
      PIN can detect a hierarchical organization of overlapping modules by tuning the
      value of   lambda. The hierarchical organization is similar to the hierarchical
      organization of GO annotations and that of the known complexes in MIPS. To
      compare the performance of OH-PIN and other existing competing algorithms, we
      apply them to the yeast PPI network. The experimental results show that OH-PIN
      outperforms the existing algorithms in terms of the functional enrichment and
      matching with known protein complexes.

PMID- 22955965
TI  - Cardiomyogenesis in the aging and failing human heart.
AB  - BACKGROUND: Two opposite views of cardiac growth are currently held; one views
      the heart as a static organ characterized by a large number of cardiomyocytes
      that are present at birth and live as long as the organism, and the other views
      the heart a highly plastic organ in which the myocyte compartment is restored
      several times during the course of life. METHODS AND RESULTS: The average age of
      cardiomyocytes, vascular endothelial cells (ECs), and fibroblasts and their
      turnover rates were measured by retrospective (14)C birth dating of cells in 19
      normal hearts 2 to 78 years of age and in 17 explanted failing hearts 22 to 70
      years of age. We report that the human heart is characterized by a significant
      turnover of ventricular myocytes, ECs, and fibroblasts, physiologically and
      pathologically. Myocyte, EC, and fibroblast renewal is very high shortly after
      birth, decreases during postnatal maturation, remains relatively constant in the
      adult organ, and increases dramatically with age. From 20 to 78 years of age, the
      adult human heart entirely replaces its myocyte, EC, and fibroblast compartment
      ~8, ~6, and ~8 times, respectively. Myocyte, EC, and fibroblast regeneration is
      further enhanced with chronic heart failure. CONCLUSIONS: The human heart is a
      highly dynamic organ that retains a remarkable degree of plasticity throughout
      life and in the presence of chronic heart failure. However, the ability to
      regenerate cardiomyocytes, vascular ECs, and fibroblasts cannot prevent the
      manifestations of myocardial aging or oppose the negative effects of ischemic and
      idiopathic dilated cardiomyopathy.

PMID- 22955968
TI  - Aminoindanol-based chiral derivatizing agents for the determination of the
      absolute configuration of carboxylic acids.
AB  - New chiral derivatizing agents have been prepared through a simple, short-step
      synthesis. The absolute configuration of alpha-chiral carboxylic acids can be
      assigned on the basis of the NMR chemical shift difference between diastereomeric
      esters. Because of the modular structures of the agents, the anisotropic effect
      could be easily manipulated to afford large chemical shift differences even in
      polar solvents.

PMID- 22955969
TI  - Respect for cultural diversity in bioethics is an ethical imperative.
AB  - The field of bioethics continues to struggle with the problem of cultural
      diversity: can universal principles guide ethical decision making, regardless of
      the culture in which those decisions take place? Or should bioethical principles
      be derived from the moral traditions of local cultures? Ten Have and Gordijn
      (Medicine, Health Care and Philosophy 14:1-3, 2011) and Bracanovic (Medicine,
      Health Care and Philosophy 14:229-236, 2011) defend the universalist position,
      arguing that respect for cultural diversity in matters ethical will lead to a
      dangerous cultural relativity where vulnerable patients and research subjects
      will be harmed. We challenge the premises of moral universalism, showing how this
      approach imports and imposes moral notions of Western society and leads to harm
      in non-western cultures. 

PMID- 22955970
TI  - The quest for Mediterranean bioethics.

PMID- 22955971
TI  - Decoding the human genome.

PMID- 22955972
TI  - What does our genome encode?
AB  - In its first production phase, The ENCODE Project Consortium (ENCODE) has
      generated thousands of genome-scale data sets, resulting in a genomic "parts
      list" that encompasses transcripts, sites of transcription factor binding, and
      other functional features that now number in the millions of distinct elements.
      These data are reshaping many long-held beliefs concerning the information
      content of the human and other complex genomes, including the very definition of
      the gene. Here I discuss and place in context many of the leading findings of
      ENCODE, as well as trends that are shaping the generation and interpretation of
      ENCODE data. Finally, I consider prospects for the future, including maximizing
      the accuracy, completeness, and utility of ENCODE data for the community.

PMID- 22955973
TI  - Toward mapping the biology of the genome.
AB  - This issue of Genome Research presents new results, methods, and tools from The
      ENCODE Project (ENCyclopedia of DNA Elements), which collectively represents an
      important step in moving beyond a parts list of the genome and promises to shape
      the future of genomic research. This collection sheds light on basic biological
      questions and frames the current debate over the optimization of tools and
      methodological challenges necessary to compare and interpret large complex data
      sets focused on how the genome is organized and regulated. In a number of
      instances, the authors have highlighted the strengths and limitations of current
      computational and technical approaches, providing the community with useful
      standards, which should stimulate development of new tools. In many ways, these
      papers will ripple through the scientific community, as those in pursuit of
      understanding the "regulatory genome" will heavily traverse the maps and tools.
      Similarly, the work should have a substantive impact on how genetic variation
      contributes to specific diseases and traits by providing a compendium of
      functional elements for follow-up study. The success of these papers should not
      only be measured by the scope of the scientific insights and tools but also by
      their ability to attract new talent to mine existing and future data.

PMID- 22955974
TI  - Deep sequencing of subcellular RNA fractions shows splicing to be predominantly
      co-transcriptional in the human genome but inefficient for lncRNAs.
AB  - Splicing remains an incompletely understood process. Recent findings suggest that
      chromatin structure participates in its regulation. Here, we analyze the RNA from
      subcellular fractions obtained through RNA-seq in the cell line K562. We show
      that in the human genome, splicing occurs predominantly during transcription. We
      introduce the coSI measure, based on RNA-seq reads mapping to exon junctions and
      borders, to assess the degree of splicing completion around internal exons. We
      show that, as expected, splicing is almost fully completed in cytosolic polyA+
      RNA. In chromatin-associated RNA (which includes the RNA that is being
      transcribed), for 5.6% of exons, the removal of the surrounding introns is fully
      completed, compared with 0.3% of exons for which no intron-removal has occurred.
      The remaining exons exist as a mixture of spliced and fewer unspliced molecules,
      with a median coSI of 0.75. Thus, most RNAs undergo splicing while being
      transcribed: "co-transcriptional splicing." Consistent with co-transcriptional
      spliceosome assembly and splicing, we have found significant enrichment of
      spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA
      fractions and other nonspliceosomal snRNAs. CoSI scores decrease along the gene,
      pointing to a "first transcribed, first spliced" rule, yet more downstream exons
      carry other characteristics, favoring rapid, co-transcriptional intron removal.
      Exons with low coSI values, that is, in the process of being spliced, are
      enriched with chromatin marks, consistent with a role for chromatin in splicing
      during transcription. For alternative exons and long noncoding RNAs, splicing
      tends to occur later, and the latter might remain unspliced in some cases.

PMID- 22955975
TI  - RNA editing in the human ENCODE RNA-seq data.
AB  - RNA-seq data can be mined for sequence differences relative to the reference
      genome to identify both genomic SNPs and RNA editing events. We analyzed the
      long, polyA-selected, unstranded, deeply sequenced RNA-seq data from the ENCODE
      Project across 14 human cell lines for candidate RNA editing events. On average,
      43% of the RNA sequencing variants that are not in dbSNP and are within gene
      boundaries are A-to-G(I) RNA editing candidates. The vast majority of A-to-G(I)
      edits are located in introns and 3' UTRs, with only 123 located in protein-coding
      sequence. In contrast, the majority of non-A-to-G variants (60%-80%) map near
      exon boundaries and have the characteristics of splice-mapping artifacts. After
      filtering out all candidates with evidence of private genomic variation using
      genome resequencing or ChIP-seq data, we find that up to 85% of the high
      confidence RNA variants are A-to-G(I) editing candidates. Genes with A-to-G(I)
      edits are enriched in Gene Ontology terms involving cell division, viral defense,
      and translation. The distribution and character of the remaining non-A-to-G
      variants closely resemble known SNPs. We find no reproducible A-to-G(I) edits
      that result in nonsynonymous substitutions in all three lymphoblastoid cell lines
      in our study, unlike RNA editing in the brain. Given that only a fraction of
      sites are reproducibly edited in multiple cell lines and that we find a stronger
      association of editing and specific genes suggests that the editing of the
      transcript is more important than the editing of any individual site.

PMID- 22955976
TI  - Discovery of hundreds of mirtrons in mouse and human small RNA data.
AB  - Atypical miRNA substrates do not fit criteria often used to annotate canonical
      miRNAs, and can escape the notice of miRNA genefinders. Recent analyses expanded
      the catalogs of invertebrate splicing-derived miRNAs ("mirtrons"), but only a few
      tens of mammalian mirtrons have been recognized to date. We performed meta
      analysis of 737 mouse and human small RNA data sets comprising 2.83 billion raw
      reads. Using strict and conservative criteria, we provide confident annotation
      for 237 mouse and 240 human splicing-derived miRNAs, the vast majority of which
      are novel genes. These comprise three classes of splicing-derived miRNAs in
      mammals: conventional mirtrons, 5'-tailed mirtrons, and 3'-tailed mirtrons. In
      addition, we segregated several hundred additional human and mouse loci with
      candidate (and often compelling) evidence. Most of these loci arose relatively
      recently in their respective lineages. Nevertheless, some members in each of the
      three mirtron classes are conserved, indicating their incorporation into
      beneficial regulatory networks. We also provide the first Northern validation for
      mammalian mirtrons, and demonstrate Dicer-dependent association of mature miRNAs
      from all three classes of mirtrons with Ago2. The recognition of hundreds of
      mammalian mirtrons provides a new foundation for understanding the scope and
      evolutionary dynamics of Dicer substrates in mammals.

PMID- 22955977
TI  - Long noncoding RNAs are rarely translated in two human cell lines.
AB  - Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human
      genome loci classified as long noncoding RNAs (lncRNAs), yet only ~100 have been
      deeply characterized to determine their role in the cell. To measure the protein
      coding output from these RNAs, we jointly analyzed two recent data sets produced
      in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed
      peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in
      long polyA+ and polyA- fractions in the cell lines K562 and GM12878. We used the
      machine-learning algorithm RuleFit3 to regress the peptide data against RNA
      expression data. The most important covariate for predicting translation was,
      surprisingly, the Cytosol polyA- fraction in both cell lines. LncRNAs are ~13
      fold less likely to produce detectable peptides than similar mRNAs, indicating
      that ~92% of GENCODE v7 lncRNAs are not translated in these two ENCODE cell
      lines. Intersecting 9640 lncRNA loci with 79,333 peptides yielded 85 unique
      peptides matching 69 lncRNAs. Most cases were due to a coding transcript
      misannotated as lncRNA. Two exceptions were an unprocessed pseudogene and a bona
      fide lncRNA gene, both with open reading frames (ORFs) compromised by upstream
      stop codons. All potentially translatable lncRNA ORFs had only a single peptide
      match, indicating low protein abundance and/or false-positive peptide matches. We
      conclude that with very few exceptions, ribosomes are able to distinguish coding
      from noncoding transcripts and, hence, that ectopic translation and cryptic mRNAs
      are rare in the human lncRNAome.

PMID- 22955978
TI  - Understanding transcriptional regulation by integrative analysis of transcription
      factor binding data.
AB  - Statistical models have been used to quantify the relationship between gene
      expression and transcription factor (TF) binding signals. Here we apply the
      models to the large-scale data generated by the ENCODE project to study
      transcriptional regulation by TFs. Our results reveal a notable difference in the
      prediction accuracy of expression levels of transcription start sites (TSSs)
      captured by different technologies and RNA extraction protocols. In general, the
      expression levels of TSSs with high CpG content are more predictable than those
      with low CpG content. For genes with alternative TSSs, the expression levels of
      downstream TSSs are more predictable than those of the upstream ones. Different
      TF categories and specific TFs vary substantially in their contributions to
      predicting expression. Between two cell lines, the differential expression of TSS
      can be precisely reflected by the difference of TF-binding signals in a
      quantitative manner, arguing against the conventional on-and-off model of TF
      binding. Finally, we explore the relationships between TF-binding signals and
      other chromatin features such as histone modifications and DNase hypersensitivity
      for determining expression. The models imply that these features regulate
      transcription in a highly coordinated manner.

PMID- 22955979
TI  - A highly integrated and complex PPARGC1A transcription factor binding network in
      HepG2 cells.
AB  - PPARGC1A is a transcriptional coactivator that binds to and coactivates a variety
      of transcription factors (TFs) to regulate the expression of target genes.
      PPARGC1A plays a pivotal role in regulating energy metabolism and has been
      implicated in several human diseases, most notably type II diabetes. Previous
      studies have focused on the interplay between PPARGC1A and individual TFs, but
      little is known about how PPARGC1A combines with all of its partners across the
      genome to regulate transcriptional dynamics. In this study, we describe a core
      PPARGC1A transcriptional regulatory network operating in HepG2 cells treated with
      forskolin. We first mapped the genome-wide binding sites of PPARGC1A using
      chromatin-IP followed by high-throughput sequencing (ChIP-seq) and uncovered
      overrepresented DNA sequence motifs corresponding to known and novel PPARGC1A
      network partners. We then profiled six of these site-specific TF partners using
      ChIP-seq and examined their network connectivity and combinatorial binding
      patterns with PPARGC1A. Our analysis revealed extensive overlap of targets
      including a novel link between PPARGC1A and HSF1, a TF regulating the conserved
      heat shock response pathway that is misregulated in diabetes. Importantly, we
      found that different combinations of TFs bound to distinct functional sets of
      genes, thereby helping to reveal the combinatorial regulatory code for metabolic
      and other cellular processes. In addition, the different TFs often bound near the
      promoters and coding regions of each other's genes suggesting an intricate
      network of interdependent regulation. Overall, our study provides an important
      framework for understanding the systems-level control of metabolic gene
      expression in humans.

PMID- 22955980
TI  - Widespread plasticity in CTCF occupancy linked to DNA methylation.
AB  - CTCF is a ubiquitously expressed regulator of fundamental genomic processes
      including transcription, intra- and interchromosomal interactions, and chromatin
      structure. Because of its critical role in genome function, CTCF binding patterns
      have long been assumed to be largely invariant across different cellular
      environments. Here we analyze genome-wide occupancy patterns of CTCF by ChIP-seq
      in 19 diverse human cell types, including normal primary cells and immortal
      lines. We observed highly reproducible yet surprisingly plastic genomic binding
      landscapes, indicative of strong cell-selective regulation of CTCF occupancy.
      Comparison with massively parallel bisulfite sequencing data indicates that 41%
      of variable CTCF binding is linked to differential DNA methylation, concentrated
      at two critical positions within the CTCF recognition sequence. Unexpectedly,
      CTCF binding patterns were markedly different in normal versus immortal cells,
      with the latter showing widespread disruption of CTCF binding associated with
      increased methylation. Strikingly, this disruption is accompanied by up
      regulation of CTCF expression, with the result that both normal and immortal
      cells maintain the same average number of CTCF occupancy sites genome-wide. These
      results reveal a tight linkage between DNA methylation and the global occupancy
      patterns of a major sequence-specific regulatory factor.

PMID- 22955981
TI  - Personal and population genomics of human regulatory variation.
AB  - The characteristics and evolutionary forces acting on regulatory variation in
      humans remains elusive because of the difficulty in defining functionally
      important noncoding DNA. Here, we combine genome-scale maps of regulatory DNA
      marked by DNase I hypersensitive sites (DHSs) from 138 cell and tissue types with
      whole-genome sequences of 53 geographically diverse individuals in order to
      better delimit the patterns of regulatory variation in humans. We estimate that
      individuals likely harbor many more functionally important variants in regulatory
      DNA compared with protein-coding regions, although they are likely to have, on
      average, smaller effect sizes. Moreover, we demonstrate that there is significant
      heterogeneity in the level of functional constraint in regulatory DNA among
      different cell types. We also find marked variability in functional constraint
      among transcription factor motifs in regulatory DNA, with sequence motifs for
      major developmental regulators, such as HOX proteins, exhibiting levels of
      constraint comparable to protein-coding regions. Finally, we perform a genome
      wide scan of recent positive selection and identify hundreds of novel substrates
      of adaptive regulatory evolution that are enriched for biologically interesting
      pathways such as melanogenesis and adipocytokine signaling. These data and
      results provide new insights into patterns of regulatory variation in individuals
      and populations and demonstrate that a large proportion of functionally important
      variation lies beyond the exome.

PMID- 22955982
TI  - Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the
      human genome.
AB  - Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein
      coding genes, pseudogenes, and noncoding transcribed loci in the human genome
      through manual curation and computational methods. Annotated transcript
      structures were assessed, and less well-supported loci were systematically,
      experimentally validated. Predicted exon-exon junctions were evaluated by RT-PCR
      amplification followed by highly multiplexed sequencing readout, a method we
      called RT-PCR-seq. Seventy-nine percent of all assessed junctions are confirmed
      by this evaluation procedure, demonstrating the high quality of the GENCODE gene
      set. RT-PCR-seq was also efficient to screen gene models predicted using the
      Human Body Map (HBM) RNA-seq data. We validated 73% of these predictions, thus
      confirming 1168 novel genes, mostly noncoding, which will further complement the
      GENCODE annotation. Our novel experimental validation pipeline is extremely
      sensitive, far more than unbiased transcriptome profiling through RNA sequencing,
      which is becoming the norm. For example, exon-exon junctions unique to GENCODE
      annotated transcripts are five times more likely to be corroborated with our
      targeted approach than with extensive large human transcriptome profiling. Data
      sets such as the HBM and ENCODE RNA-seq data fail sampling of low-expressed
      transcripts. Our RT-PCR-seq targeted approach also has the advantage of
      identifying novel exons of known genes, as we discovered unannotated exons in
      ~11% of assessed introns. We thus estimate that at least 18% of known loci have
      yet-unannotated exons. Our work demonstrates that the cataloging of all of the
      genic elements encoded in the human genome will necessitate a coordinated effort
      between unbiased and targeted approaches, like RNA-seq and RT-PCR-seq.

PMID- 22955983
TI  - Predicting cell-type-specific gene expression from regions of open chromatin.
AB  - Complex patterns of cell-type-specific gene expression are thought to be achieved
      by combinatorial binding of transcription factors (TFs) to sequence elements in
      regulatory regions. Predicting cell-type-specific expression in mammals has been
      hindered by the oftentimes unknown location of distal regulatory regions. To
      alleviate this bottleneck, we used DNase-seq data from 19 diverse human cell
      types to identify proximal and distal regulatory elements at genome-wide scale.
      Matched expression data allowed us to separate genes into classes of cell-type
      specific up-regulated, down-regulated, and constitutively expressed genes. CG
      dinucleotide content and DNA accessibility in the promoters of these three
      classes of genes displayed substantial differences, highlighting the importance
      of including these aspects in modeling gene expression. We associated DNase I
      hypersensitive sites (DHSs) with genes, and trained classifiers for different
      expression patterns. TF sequence motif matches in DHSs provided a strong
      performance improvement in predicting gene expression over the typical baseline
      approach of using proximal promoter sequences. In particular, we achieved
      competitive performance when discriminating up-regulated genes from different
      cell types or genes up- and down-regulated under the same conditions. We
      identified previously known and new candidate cell-type-specific regulators. The
      models generated testable predictions of activating or repressive functions of
      regulators. DNase I footprints for these regulators were indicative of their
      direct binding to DNA. In summary, we successfully used information of open
      chromatin obtained by a single assay, DNase-seq, to address the problem of
      predicting cell-type-specific gene expression in mammalian organisms directly
      from regulatory sequence.

PMID- 22955984
TI  - Sequence and chromatin determinants of cell-type-specific transcription factor
      binding.
AB  - Gene regulatory programs in distinct cell types are maintained in large part
      through the cell-type-specific binding of transcription factors (TFs). The
      determinants of TF binding include direct DNA sequence preferences, DNA sequence
      preferences of cofactors, and the local cell-dependent chromatin context. To
      explore the contribution of DNA sequence signal, histone modifications, and DNase
      accessibility to cell-type-specific binding, we analyzed 286 ChIP-seq experiments
      performed by the ENCODE Consortium. This analysis included experiments for 67
      transcriptional regulators, 15 of which were profiled in both the GM12878
      (lymphoblastoid) and K562 (erythroleukemic) human hematopoietic cell lines. To
      model TF-bound regions, we trained support vector machines (SVMs) that use
      flexible k-mer patterns to capture DNA sequence signals more accurately than
      traditional motif approaches. In addition, we trained SVM spatial chromatin
      signatures to model local histone modifications and DNase accessibility,
      obtaining significantly more accurate TF occupancy predictions than simpler
      approaches. Consistent with previous studies, we find that DNase accessibility
      can explain cell-line-specific binding for many factors. However, we also find
      that of the 10 factors with prominent cell-type-specific binding patterns, four
      display distinct cell-type-specific DNA sequence preferences according to our
      models. Moreover, for two factors we identify cell-specific binding sites that
      are accessible in both cell types but bound only in one. For these sites, cell
      type-specific sequence models, rather than DNase accessibility, are better able
      to explain differential binding. Our results suggest that using a single motif
      for each TF and filtering for chromatin accessible loci is not always sufficient
      to accurately account for cell-type-specific binding profiles.

PMID- 22955985
TI  - Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory
      elements.
AB  - Gene regulation at functional elements (e.g., enhancers, promoters, insulators)
      is governed by an interplay of nucleosome remodeling, histone modifications, and
      transcription factor binding. To enhance our understanding of gene regulation,
      the ENCODE Consortium has generated a wealth of ChIP-seq data on DNA-binding
      proteins and histone modifications. We additionally generated nucleosome
      positioning data on two cell lines, K562 and GM12878, by MNase digestion and high
      depth sequencing. Here we relate 14 chromatin signals (12 histone marks, DNase,
      and nucleosome positioning) to the binding sites of 119 DNA-binding proteins
      across a large number of cell lines. We developed a new method for unsupervised
      pattern discovery, the Clustered AGgregation Tool (CAGT), which accounts for the
      inherent heterogeneity in signal magnitude, shape, and implicit strand
      orientation of chromatin marks. We applied CAGT on a total of 5084 data set pairs
      to obtain an exhaustive catalog of high-resolution patterns of histone
      modifications and nucleosome positioning signals around bound transcription
      factors. Our analyses reveal extensive heterogeneity in how histone modifications
      are deposited, and how nucleosomes are positioned around binding sites. With the
      exception of the CTCF/cohesin complex, asymmetry of nucleosome positioning is
      predominant. Asymmetry of histone modifications is also widespread, for all types
      of chromatin marks examined, including promoter, enhancer, elongation, and
      repressive marks. The fine-resolution signal shapes discovered by CAGT unveiled
      novel correlation patterns between chromatin marks, nucleosome positioning, and
      sequence content. Meta-analyses of the signal profiles revealed a common
      vocabulary of chromatin signals shared across multiple cell lines and binding
      proteins.

PMID- 22955986
TI  - Linking disease associations with regulatory information in the human genome.
AB  - Genome-wide association studies have been successful in identifying single
      nucleotide polymorphisms (SNPs) associated with a large number of phenotypes.
      However, an associated SNP is likely part of a larger region of linkage
      disequilibrium. This makes it difficult to precisely identify the SNPs that have
      a biological link with the phenotype. We have systematically investigated the
      association of multiple types of ENCODE data with disease-associated SNPs and
      show that there is significant enrichment for functional SNPs among the currently
      identified associations. This enrichment is strongest when integrating multiple
      sources of functional information and when highest confidence disease-associated
      SNPs are used. We propose an approach that integrates multiple types of
      functional data generated by the ENCODE Consortium to help identify "functional
      SNPs" that may be associated with the disease phenotype. Our approach generates
      putative functional annotations for up to 80% of all previously reported
      associations. We show that for most associations, the functional SNP most
      strongly supported by experimental evidence is a SNP in linkage disequilibrium
      with the reported association rather than the reported SNP itself. Our results
      show that the experimental data sets generated by the ENCODE Consortium can be
      successfully used to suggest functional hypotheses for variants associated with
      diseases and other phenotypes.

PMID- 22955987
TI  - GENCODE: the reference human genome annotation for The ENCODE Project.
AB  - The GENCODE Consortium aims to identify all gene features in the human genome
      using a combination of computational analysis, manual annotation, and
      experimental validation. Since the first public release of this annotation data
      set, few new protein-coding loci have been added, yet the number of alternative
      splicing transcripts annotated has steadily increased. The GENCODE 7 release
      contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977
      coding transcripts not represented in UCSC genes and RefSeq. It also has the most
      comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available
      with the predominant transcript form consisting of two exons. We have examined
      the completeness of the transcript annotation and found that 35% of
      transcriptional start sites are supported by CAGE clusters and 62% of protein
      coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding
      genes are supported by peptide hits derived from mass spectrometry spectra
      submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA
      seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist
      of two exon models indicating that they are possibly unannotated long noncoding
      loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl
      and UCSC Genome Browsers.

PMID- 22955988
TI  - The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene
      structure, evolution, and expression.
AB  - The human genome contains many thousands of long noncoding RNAs (lncRNAs). While
      several studies have demonstrated compelling biological and disease roles for
      individual examples, analytical and experimental approaches to investigate these
      genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we
      present and analyze the most complete human lncRNA annotation to date, produced
      by the GENCODE consortium within the framework of the ENCODE project and
      comprising 9277 manually annotated genes producing 14,880 transcripts. Our
      analyses indicate that lncRNAs are generated through pathways similar to that of
      protein-coding genes, with similar histone-modification profiles, splicing
      signals, and exon/intron lengths. In contrast to protein-coding genes, however,
      lncRNAs display a striking bias toward two-exon transcripts, they are
      predominantly localized in the chromatin and nucleus, and a fraction appear to be
      preferentially processed into small RNAs. They are under stronger selective
      pressure than neutrally evolving sequences-particularly in their promoter
      regions, which display levels of selection comparable to protein-coding genes.
      Importantly, about one-third seem to have arisen within the primate lineage.
      Comprehensive analysis of their expression in multiple human organs and brain
      regions shows that lncRNAs are generally lower expressed than protein-coding
      genes, and display more tissue-specific expression patterns, with a large
      fraction of tissue-specific lncRNAs expressed in the brain. Expression
      correlation analysis indicates that lncRNAs show particularly striking positive
      correlation with the expression of antisense coding genes. This GENCODE
      annotation represents a valuable resource for future studies of lncRNAs.

PMID- 22955989
TI  - Annotation of functional variation in personal genomes using RegulomeDB.
AB  - As the sequencing of healthy and disease genomes becomes more commonplace,
      detailed annotation provides interpretation for individual variation responsible
      for normal and disease phenotypes. Current approaches focus on direct changes in
      protein coding genes, particularly nonsynonymous mutations that directly affect
      the gene product. However, most individual variation occurs outside of genes and,
      indeed, most markers generated from genome-wide association studies (GWAS)
      identify variants outside of coding segments. Identification of potential
      regulatory changes that perturb these sites will lead to a better localization of
      truly functional variants and interpretation of their effects. We have developed
      a novel approach and database, RegulomeDB, which guides interpretation of
      regulatory variants in the human genome. RegulomeDB includes high-throughput,
      experimental data sets from ENCODE and other sources, as well as computational
      predictions and manual annotations to identify putative regulatory potential and
      identify functional variants. These data sources are combined into a powerful
      tool that scores variants to help separate functional variants from a large pool
      and provides a small set of putative sites with testable hypotheses as to their
      function. We demonstrate the applicability of this tool to the annotation of
      noncoding variants from 69 full sequenced genomes as well as that of a personal
      genome, where thousands of functionally associated variants were identified.
      Moreover, we demonstrate a GWAS where the database is able to quickly identify
      the known associated functional variant and provide a hypothesis as to its
      function. Overall, we expect this approach and resource to be valuable for the
      annotation of human genome sequences.

PMID- 22955990
TI  - Sequence features and chromatin structure around the genomic regions bound by 119
      human transcription factors.
AB  - Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq)
      has become the dominant technique for mapping transcription factor (TF) binding
      regions genome-wide. We performed an integrative analysis centered around 457
      ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We
      identified highly enriched sequence motifs in most data sets, revealing new
      motifs and validating known ones. The motif sites (TF binding sites) are highly
      conserved evolutionarily and show distinct footprints upon DNase I digestion. We
      frequently detected secondary motifs in addition to the canonical motifs of the
      TFs, indicating tethered binding and cobinding between multiple TFs. We observed
      significant position and orientation preferences between many cobinding TFs.
      Genes specifically expressed in a cell line are often associated with a greater
      occurrence of nearby TF binding in that cell line. We observed cell-line-specific
      secondary motifs that mediate the binding of the histone deacetylase HDAC2 and
      the enhancer-binding protein EP300. TF binding sites are located in GC-rich,
      nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned
      nucleosomes, and many of these features show cell type specificity. The GC
      richness may be beneficial for regulating TF binding because, when unoccupied by
      a TF, these regions are occupied by nucleosomes in vivo. We present the results
      of our analysis in a TF-centric web repository Factorbook (http://factorbook.org)
      and will continually update this repository as more ENCODE data are generated.

PMID- 22955992
TI  - Lipid levels do not influence the risk of venous thromboembolism. Results of a
      population-based cohort study.
AB  - Studies on the association between lipid profile and venous thromboembolism (VTE)
      are inconsistent. This could be caused by classical lipoproteins being inferior
      to apolipoproteins as markers for VTE risk. Therefore, we examined whether
      apolipoproteins are more strongly related to VTE than lipoproteins. For this
      analysis we used the PREVEND prospective community based observational cohort
      study. Levels of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total
      cholesterol (TC), high-density lipoprotein (HDL), non-HDL, low-density
      lipoprotein (LDL), triglycerides (TG), lipoprotein(a), ApoB/ApoA1 and TC/HDL
      ratio were assessed. Subjects with VTE were identified using databases of the
      national registries of hospital discharge diagnoses, death certificates, and the
      regional anticoagulation clinic. Out of 7,627 subjects, 110 developed VTE during
      a median follow-up of 10.5 years. In both univariate and multivariable analyses
      no significant associations between apolipoproteins and overall VTE were
      observed. Of the classical lipoproteins, TC, non-HDL, LDL, TG, and TC/HDL ratio
      were significantly associated with overall VTE in univariate analysis.
      Significant associations were no longer present in multivariable analysis. TGL
      and LDL were significantly associated with unprovoked VTE in univariate analysis.
      After adjustment for age and sex this significance was lost. No significant
      associations between (apo-) lipoproteins and provoked VTE were found. We conclude
      that apolipoproteins are not better in predicting VTE risk than the classical
      lipoproteins. Our population-based cohort study does not show an association
      between both apolipoproteins and the classical lipoproteins and VTE risk.

PMID- 22955991
TI  - ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.
AB  - Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing
      (ChIP-seq) has become a valuable and widely used approach for mapping the genomic
      location of transcription-factor binding and histone modifications in living
      cells. Despite its widespread use, there are considerable differences in how
      these experiments are conducted, how the results are scored and evaluated for
      quality, and how the data and metadata are archived for public use. These
      practices affect the quality and utility of any global ChIP experiment. Through
      our experience in performing ChIP-seq experiments, the ENCODE and modENCODE
      consortia have developed a set of working standards and guidelines for ChIP
      experiments that are updated routinely. The current guidelines address antibody
      validation, experimental replication, sequencing depth, data and metadata
      reporting, and data quality assessment. We discuss how ChIP quality, assessed in
      these ways, affects different uses of ChIP-seq data. All data sets used in the
      analysis have been deposited for public viewing and downloading at the ENCODE
      (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/)
      portals.

PMID- 22955993
TI  - Adult glucose metabolism in extremely birthweight-discordant monozygotic twins.
AB  - AIMS/HYPOTHESIS: Low birthweight (BW) is associated with increased risk of type 2
      diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ)
      twins, thereby controlling for genetic factors and rearing environment. METHODS:
      Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ
      twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose
      tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose
      dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta
      cell function (HOMA-beta) and insulin resistance (HOMA-IR), and also insulin
      sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were
      calculated. Subgroup analyses were performed in those with: (1) double
      verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt
      metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease). RESULTS:
      No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones,
      HOMA-beta, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher
      in the twins with the highest BW without metabolic disease, and BIGTT-AIR was
      higher in those with the highest BW although not in pairs with a BW difference of
      >0.5 kg. CONCLUSIONS/INTERPRETATION: BW-discordant MZ twins provide no evidence
      for a detrimental effect of low BW on glucose metabolism in adulthood once
      genetic factors and rearing environment are controlled for.

PMID- 22955994
TI  - Protection from non-alcoholic steatohepatitis and liver tumourigenesis in high
      fat-fed insulin receptor substrate-1-knockout mice despite insulin resistance.
AB  - AIMS/HYPOTHESIS: Epidemiological studies have revealed that obesity and diabetes
      mellitus are independent risk factors for the development of non-alcoholic
      steatohepatitis (NASH) and hepatocellular carcinoma. However, the debate
      continues on whether insulin resistance as such is directly associated with NASH
      and liver tumourigenesis. Here, we investigated the incidence of NASH and liver
      tumourigenesis in Irs1 ( -/- ) mice subjected to a long-term high-fat (HF) diet.
      Our hypothesis was that hepatic steatosis, rather than insulin resistance may be
      related to the pathophysiology of these conditions. METHODS: Mice (8 weeks old,
      C57Bl/6J) were given free access to standard chow (SC) or an HF diet. The
      development of NASH and liver tumourigenesis was evaluated after mice had been on
      the above-mentioned diets for 60 weeks. Similarly, Irs1 ( -/- ) mice were also
      subjected to an HF diet for 60 weeks. RESULTS: Long-term HF diet loading, which
      causes obesity and insulin resistance, was sufficient to induce NASH and liver
      tumourigenesis in the C57Bl/6J mice. Obesity and insulin resistance were reduced
      by switching mice from the HF diet to SC, which also protected these mice against
      the development of NASH and liver tumourigenesis. However, compared with wild
      type mice fed the HF diet, Irs1 ( -/- ) mice fed the HF diet were dramatically
      protected against NASH and liver tumourigenesis despite the presence of severe
      insulin resistance and marked postprandial hyperglycaemia.
      CONCLUSIONS/INTERPRETATION: IRS-1 inhibition might protect against HF diet
      induced NASH and liver tumourigenesis, despite the presence of insulin
      resistance.

PMID- 22955995
TI  - Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with
      higher risk of insulin-requiring diabetes: a nested case-control study.
AB  - AIMS/HYPOTHESIS: Low serum 25-hydroxyvitamin D [25(OH)D] concentration may
      increase risk of insulin-requiring diabetes. METHODS: A nested case-control study
      was performed using serum collected during 2002-2008 from military service
      members. One thousand subjects subsequently developed insulin-requiring diabetes.
      A healthy control was individually matched to each case on blood-draw date (+/-2
      days), age (+/-3 months), length of service (+/-30 days) and sex. The median
      elapsed time between serum collection and first diagnosis of diabetes was 1 year
      (range 1 month to 10 years). Statistical analysis used matched pairs and
      conditional logistic regression. RESULTS: ORs for insulin-requiring diabetes by
      quintile of serum 25(OH)D, from lowest to highest, were 3.5 (95% CI 2.0, 6.0),
      2.5 (1.5, 4.2), 0.8 (0.4, 1.4), 1.1 (0.6, 2.8) and 1.0 (reference) (p (trend)
      <0.001). The quintiles (based on fifths using serum 25(OH)D concentration in the
      controls) of serum 25(OH)D in nmol/l, were <43 (median 28), 43-59 (median 52), 60
      77 (median 70), 78-99 (median 88) and >=100 (median 128).
      CONCLUSIONS/INTERPRETATION: Individuals with lower serum 25(OH)D concentrations
      had higher risk of insulin-requiring diabetes than those with higher
      concentrations. A 3.5-fold lower risk was associated with a serum 25(OH)D
      concentration >=60 nmol/l.

PMID- 22955997
TI  - Sudden bilateral anterior cerebral infarction: unusual stroke associated with
      unusual vascular anomalies.

PMID- 22955996
TI  - Development of a new scoring system for predicting the 5 year incidence of type 2
      diabetes in Japan: the Toranomon Hospital Health Management Center Study 6
      (TOPICS 6).
AB  - AIMS/HYPOTHESIS: The aims of this study were to assess the clinical significance
      of introducing HbA(1c) into a risk score for diabetes and to develop a scoring
      system to predict the 5 year incidence of diabetes in Japanese individuals.
      METHODS: The study included 7,654 non-diabetic individuals aged 40-75 years.
      Incident diabetes was defined as fasting plasma glucose (FPG) >=7.0 mmol/l,
      HbA(1c) >=6.5% (48 mmol/mol) or self-reported clinician-diagnosed diabetes. We
      constructed a risk score using non-laboratory assessments (NLA) and evaluated
      improvements in risk prediction by adding elevated FPG, elevated HbA(1c) or both
      to NLA. RESULTS: The discriminative ability of the NLA score (age, sex, family
      history of diabetes, current smoking and BMI) was 0.708. The difference in
      discrimination between the NLA + FPG and NLA + HbA(1c) scores was non-significant
      (0.836 vs 0.837; p = 0.898). A risk score including family history of diabetes,
      smoking, obesity and both FPG and HbA(1c) had the highest discrimination (0.887,
      95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity
      were high at 83.7% and 79.0%, respectively. After initial screening using NLA
      scores, subsequent information on either FPG or HbA(1c) resulted in a net
      reclassification improvement of 42.7% or 52.3%, respectively (p < 0.0001). When
      both were available, net reclassification improvement and integrated
      discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%)
      and 10.9% (9.7%, 12.1%), respectively. CONCLUSIONS/INTERPRETATION: Information on
      HbA(1c) or FPG levels after initial screening by NLA can precisely refine
      diabetes risk reclassification.

PMID- 22955998
TI  - Robotic versus laparoscopic adrenalectomy: a comparative study in a high-volume
      center.
AB  - BACKGROUND: Minimally invasive surgery has become more popular in recent years.
      The da Vinci robot is one of the new technologies the use of which has gained
      popularity in a host of different specialties. Originally used in cardiac
      surgery, marked increases in utilization have been seen in urology, gynecology,
      and thoracic surgery. Use in general surgical procedures has now become more
      common. The objective benefits of the robot are unclear compared to those of
      laparoscopy in many procedures. The aim of this study was to assess the benefits
      and disadvantages of robot-assisted laparoscopic surgery for adrenalectomy in a
      high-volume center compared to routine laparoscopic techniques. METHODS: We
      conducted a retrospective study including consecutive patients who underwent
      minimally invasive adrenalectomy in a tertiary referral center at the University
      of Alabama Birmingham. Demographic, clinical, histopathological, and surgical
      variables were recorded. Patients were divided in two groups: laparoscopic
      adrenalectomy (LA) and robot-assisted adrenalectomy (RA). Groups were compared
      using the chi(2) test for categorical variables and Student's t-test for
      continuous variables. Significance was considered p < 0.05. RESULTS: Sixty
      patients were included, with 30 patients in each group. There were no significant
      differences between groups with respect to demographic variables except there
      were more pheochromocytoma patients in the LA group than in the RA group (13/30
      vs. 5/30, respectively; p = 0.02). This study demonstrated increased operative
      time in the robotic group (190 +/- 33 min) versus the laparoscopic group (160 +/-
      41 min) (p = 0.003). There was a trend for less blood loss in RA versus LA (30 +/
      5 ml vs. 55 +/- 74 ml; p = 0.07). There was no mortality. Morbidity and length
      of hospital stay were similar for both groups. CONCLUSIONS: Robotic adrenalectomy
      is as safe and technically feasible as laparoscopic adrenalectomy. Subjective
      benefits for the surgeon with robot-assisted surgery include three-dimensional
      operative view, ergonomically comfortable position, and elimination of the
      surgeon's tremor. The operating time is significantly longer but patient outcomes
      are similar to those of the laparoscopic technique.

PMID- 22955999
TI  - Laparoscopy impacts outcomes favorably following colectomy for ulcerative
      colitis: a critical analysis of the ACS-NSQIP database.
AB  - INTRODUCTION: The surgical management of ulcerative colitis (UC) often involves
      complex operations. We investigated the outcome of patients who underwent surgery
      for UC by analyzing a nationwide database. METHODS: We queried the American
      College of Surgeons National Surgical Quality Improvement Program database (ACS
      NSQIP, 2005-2008) for all UC patients who underwent colectomy. To analyze by
      operation, groupings included: partial colectomy (PC; n = 265), total abdominal
      colectomy (TAC; n = 232), total proctocolectomy with ileostomy (TPC-I; n = 134),
      and total proctocolectomy with ileal pouch-anal anastomosis (IPAA; n = 446) to
      analyze 30-day outcomes. RESULTS: From 1,077 patients (mean age, 44 years; 45 %
      female; 7 % emergent), a laparoscopic approach was used in 29.2 %, with rates
      increasing 8.5 % each year (18.5 % in 2005 to 41.3 % in 2008, P < 0.001).
      Complications occurred in 29 %, and laparoscopy was associated with a lower
      complication rate (21 vs. 32 % open, P < 0.001). On multivariate regression,
      postoperative complications increased when patients were not functionally
      independent [odds ratio (OR) = 3.2], had preoperative sepsis (OR = 2.0), or prior
      percutaneous coronary intervention (OR = 2.8). A laparoscopic approach was
      associated with a lower complication rate (OR = 0.63). When stratified by
      specific complications, laparoscopy was associated with lower complications,
      including superficial surgical site infections (11.4 vs. 6.7 %, P = 0.0011),
      pneumonia (2.9 vs. 0.6 %, P = 0.023), prolonged mechanical ventilation (3.9 vs.
      1.3 %, P = 0.023), need for transfusions postoperatively (1.6 vs. 0 %, P =
      0.016), and severe sepsis (2.9 vs. 1.0 %, P = 0.039). Laparoscopy was also was
      associated with a lower complication rate in TACs (41.7 vs. 18.8 %, P < 0.0001)
      and IPAA (29.9 vs. 18.2 %, P = 0.005) and had an overall lower mortality rate
      (0.2 vs. 1.7 %, P = 0.046). CONCLUSIONS: Results from a large nationwide database
      demonstrate that a laparoscopic approach was utilized in an increasing number of
      UC patients undergoing colectomy and was associated with lower morbidity and
      mortality, even in more complex procedures, such as TAC and IPAA.

PMID- 22956000
TI  - You must be the change you wish to see in the world: Society of American
      Gastrointestinal and Endoscopic Surgeons Presidential Address 2012.

PMID- 22956002
TI  - Percutaneous radiological gastrostomy in esophageal cancer patients: a feasible
      and safe access for nutritional support during multimodal therapy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy is not widely used in
      malnourished esophageal cancer (EC) patients because of concerns about its
      feasibility in frequently obstructive tumors, suitability of the stomach as an
      esophageal substitute, and potential for metastatic inoculation. A percutaneous
      radiological gastrostomy (PRG) could be an optimal alternative. METHODS:
      Experience with PRG among 1,205 consecutive patients presenting with EC from 2002
      to 2011 in our department was retrospectively reviewed. PRG was mostly utilized
      for malnourished patients for whom neoadjuvant chemoradiation was scheduled. The
      rates of both successful placement and major related complications (Dindo-Clavien
      >=III) were analyzed. A matched cohort analysis was constructed in patients who
      underwent esophagectomy with gastroplasty (n = 688) to evaluate the impact of PRG
      placement on the suitability of the gastric conduit and on postoperative course.
      For 78 resected patients with PRG (PRG group), 156 randomly selected controls
      without PRG (no PRG group) were matched 2:1 for gender, age, ASA grade, clinical
      TNM stage, and neoadjuvant treatment delivery. RESULTS: PRG placement was planned
      in 269 (22.3 %) patients mainly with locally advanced EC (63.8 %). PRG placement
      was feasible in 259 (96.3 %) patients. Sixty-day PRG-related mortality and major
      morbidity rates were 0 and 3.8 % respectively. For resected patients, the PRG and
      no PRG groups were comparable regarding perioperative characteristics, except for
      malnutrition, which was more frequent in the PRG group (P < 0.001). At the time
      of operation, PRG takedown and site closure were uncomplicated and the use of the
      stomach was possible in all 78 patients. Despite a higher malnutrition rate at
      presentation in the PRG group, rates of overall morbidity, and morbidity related
      to esophageal surgery, were similar between the two groups (P > 0.258).
      CONCLUSION: PRG is feasible, safe, and useful in nonselected patients with EC and
      does not compromise the suitability of the stomach as an esophageal substitute in
      patients deemed to be resectable.

PMID- 22956003
TI  - Concurrent validity of questions on arm, shoulder and neck symptoms of the RSI
      QuickScan.
AB  - PURPOSE: The objective was to determine the concurrent validity of questions on
      arm, shoulder and neck symptoms of an Internet-based questionnaire. In addition,
      the inter-observer reliability of physical examinations by occupational
      physicians was investigated. METHODS: A total of 160 employees of a Dutch
      occupational health service were approached, of which 106 participated. Right
      after the assessment of arm, shoulder and neck symptoms using a self-administered
      questionnaire, each participant was examined by two occupational physicians. The
      presence of symptoms in the past 7 days was compared to the physical
      examinations. The participation of two occupational physicians allowed us to
      study also the inter-observer reliability. RESULTS: Overall, the concurrent
      validity of the symptom questions of the questionnaire can be defined as poor to
      moderate with kappa values between 0.16 and 0.53. Detecting the presence of
      symptoms (p(pos)) could be considered as moderately valid with values below 0.60,
      but the p(neg) shows that the concurrent validity for detecting the absence of
      arm, shoulder or neck symptoms can be considered sufficient with values above
      0.69. The agreement between occupational physicians can, with a few exceptions,
      be considered as moderate with kappa values below 0.60. The agreement was
      sufficient for detecting the absence of symptoms (p(neg) > 0.7). CONCLUSIONS: The
      agreement between the symptom questions of the questionnaire and physical
      examinations of occupational physicians can be considered as poor to moderate.
      The results are comparable to what is generally reported in the literature.
      Future studies should be aimed at gaining more fundamental knowledge about the
      possible conceptual differences between self-reported symptoms and symptoms
      assessed using physical examinations. Moreover, it is advisable to improve the
      inter-observer reliability of physical examinations as applied in the present
      study.

PMID- 22956001
TI  - Procedural virtual reality simulation in minimally invasive surgery.
AB  - BACKGROUND: Simulation of procedural tasks has the potential to bridge the gap
      between basic skills training outside the operating room (OR) and performance of
      complex surgical tasks in the OR. This paper provides an overview of procedural
      virtual reality (VR) simulation currently available on the market and presented
      in scientific literature for laparoscopy (LS), flexible gastrointestinal
      endoscopy (FGE), and endovascular surgery (EVS). METHODS: An online survey was
      sent to companies and research groups selling or developing procedural VR
      simulators, and a systematic search was done for scientific publications
      presenting or applying VR simulators to train or assess procedural skills in the
      PUBMED and SCOPUS databases. RESULTS: The results of five simulator companies
      were included in the survey. In the literature review, 116 articles were analyzed
      (45 on LS, 43 on FGE, 28 on EVS), presenting a total of 23 simulator systems. The
      companies stated to altogether offer 78 procedural tasks (33 for LS, 12 for FGE,
      33 for EVS), of which 17 also were found in the literature review. Although study
      type and used outcomes vary between the three different fields, approximately 90
      % of the studies presented in the retrieved publications for LS found convincing
      evidence to confirm the validity or added value of procedural VR simulation. This
      was the case in approximately 75 % for FGE and EVS. CONCLUSIONS: Procedural
      training using VR simulators has been found to improve clinical performance.
      There is nevertheless a large amount of simulated procedural tasks that have not
      been validated. Future research should focus on the optimal use of procedural
      simulators in the most effective training setups and further investigate the
      benefits of procedural VR simulation to improve clinical outcome.

PMID- 22956004
TI  - Angiolymphoid hyperplasia with eosinophilia--an incidental finding after surgical
      excision.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign
      vasoproliferative lesion. Although it is a benign disease, lesions are often
      persistent and difficult to eradicate. ALHE typically presents clinically as
      papules or nodules, tan, brown, pink or dull red in colour, located predominantly
      in the head and neck region, especially around the ears and on the forehead and
      scalp.All races can be affected and no gender predominance exists. The disease
      also has nonspecific clinical features, hence it requires in most of the cases
      biopsy for accurate diagnosis. We present an uncommon clinical presentation of
      the disease, mimicking clinically a subcutaneous lipomatous mass, which has been
      treated successfully with surgical excision.

PMID- 22956005
TI  - A modified technology could significantly improve the visualization rate of the
      internal mammary sentinel lymph nodes in breast cancer patients.

PMID- 22956006
TI  - A randomized double-blind placebo-controlled cross-over trial of the impact on
      quality of life of continuing dexamethasone beyond 24 h following adjuvant
      chemotherapy for breast cancer.
AB  - Uncertainty remains about the optimal anti-emetic regimen for control of delayed
      nausea and vomiting after adjuvant chemotherapy for breast cancer. Many patients
      receive dexamethasone but complain of insomnia, anxiety/agitation, and
      indigestion. The aim was to determine if patients receiving chemotherapy for
      breast cancer prefer treatment with dexamethasone or placebo for prophylaxis
      against delayed nausea and vomiting, and to compare quality of life (QOL) between
      the two treatments. In this randomized, double-blind, cross-over trial, we
      compared oral dexamethasone (4 mg twice daily for 2 days) versus placebo for
      chemotherapy-naive patients with breast cancer. All patients received intravenous
      granisetron and dexamethasone pre-chemotherapy and oral granisetron on day 2.
      Primary endpoints were: (i) patient preference; (ii) difference between cycles in
      change of QOL from days 1 to 8. Median age of the 94 women was 51 years (range 27
      76): 79 received fluorouracil/epirubicin/cyclophosphamide and 15 received
      doxorubicin/cyclophosphamide. Thirteen withdrew pre-cycle 2 with no differences
      between arms. Of 80 patients stating a preference, 31 preferred placebo (39 %, 95
      % CI: 28-50 %) and 37 (46 %, 95 % CI: 35-58 %) preferred dexamethasone; 12 had no
      preference. There were no differences in intensity of vomiting, nausea, or time
      to onset of vomiting. There was greater decrease in global QOL (p = 0.06) when
      patients received dexamethasone. No other symptom/QOL domains differed
      significantly. In conclusion, no significant difference was found in patient
      preference, QOL, or symptoms regardless of whether dexamethasone or placebo was
      used after adjuvant chemotherapy.

PMID- 22956008
TI  - Tetranuclear stiboxanes (RSb)4O6, exhibiting an adamantane-type structure.
AB  - Depolymerization reactions of organostibonic acids with protic ligands have been
      investigated. Reaction of arylstibonic acids with 8-hydroxyquinoline (8-HQ), or
      {2-[1H-pyrazol-5(3)-yl]naphthalene-1-ol} (H(2)naphpz) in a 1 : 1 stoichiometry in
      refluxing toluene affords adamantane-like L(4)(RSb)(4)O(6) clusters [(p
      XC(6)H(4)Sb)(4)(O)(6)(Q)(4)] (where X = Cl (1), Br (2), QH = 8-hydroxyquinoline),
      [(p-ClC(6)H(4)Sb)(4)(O)(6)(Hnaphpz)(4)].H(2)naphpz (3) and [(p-Br
      C(6)H(4)Sb)(4)(O)(6)(Hnaphpz)(4)](2).H(2)naphpz (4). Further a tetrameric
      organoantimony oxo cluster, L(4)(RSb)(4)O(4) [(p
      ClC(6)H(4)Sb)(4)(O)(4)(naphpz)(4)] (5) has also been isolated as a side product
      in the reaction of arylstibonic acid with naphthylphenolic pyrazole.
      Interestingly 1-4 structurally resemble the dimeric form of the antimony oxide
      Sb(2)O(3) and its mineral senarmontite.

PMID- 22956007
TI  - Management of small HER2 overexpressing tumours.
AB  - Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in
      10-20 % of breast cancers and is associated with a worse prognosis. Several large
      studies have established the addition of trastuzumab to chemotherapy as the gold
      standard in early breast cancer that overexpresses HER2. Little is known about
      the role of such adjuvant treatment in node-negative subcentimeter tumours
      ('small tumours', pT1a/b) because these patients were generally excluded from the
      pivotal trials. Only the BCIRG006 study published in 2011 included such tumours
      if high-risk features were present. Here we review the literature of small HER2
      positive tumours and present a meta-analysis of retrospective studies confirming
      a worse outcome in terms of disease-free survival (hazard ratio 2.6, p < 0.001)
      and a trend for higher odds of distant recurrence at 5 years (odds ratio [OR]
      2.51, p = 0.11). We discuss these findings in the light of the increased risk of
      grade 3 and 4 cardiac toxicity (OR 7.6, p < 0.001) and other adverse events
      associated with the use of trastuzumab. Such treatment may well be a valuable
      option in selected patients with high-risk features but physicians should
      exercise caution given the small absolute benefits of adjuvant chemotherapy and
      trastuzumab for patients with small HER2-overexpressing tumours.

PMID- 22956009
TI  - Paucisymptomatic infectious prostatitis as a cause of fever without an apparent
      origin. A series of 19 patients.
AB  - According to the literature, prostatitis is a rare cause of prolonged fever
      without an apparent origin. However, this syndrome can be easily diagnosed using
      specific tests, either two-glass pre- and post-prostatic massage or the Meares
      Stamey four-glass test. A retrospective study over a 5-year period (between
      August 1st 2006 and July 31st 2011) was performed. All patients who met the
      criteria for microbiological prostatitis were included and assigned to one of two
      groups, either a study group [paucisymptomatic infectious prostatitis (PIP)] or a
      control group [classic infectious prostatitis (CIP)]. Epidemiological, clinical,
      microbiological, and treatment-related variables were collected. A comparative
      study between both groups was performed. Thirty-nine patients were diagnosed with
      prostatitis. The main risk factors were unprotected anal intercourse, human
      immunodeficiency virus (HIV) infection, recent travel, and recurrent urinary
      tract infections. The most significant differences between the PIP (19 patients)
      and CIP (20 patients) groups were higher frequency of elevated inflammatory
      markers, higher frequency of monomicrobial etiology, and longer treatment. In
      monomicrobial prostatitis, the most common causative agents were coagulase
      negative Staphylococcus spp., Escherichia coli, and Corynebacterium
      glucuronolyticum. According to the findings of this study, we believe that
      prostatitis should be included as a possible diagnosis in a man who complains of
      prolonged fever without an apparent origin and having at least one of the
      following risk factors: unprotected anal intercourse, HIV infection, recent
      travel, and recurrent urinary tract infections.

PMID- 22956010
TI  - Genetic structure of Aspergillus flavus populations in human and avian isolates.
AB  - Aspergillus flavus is the second leading cause of allergic, invasive, and
      colonizing fungal diseases in humans, and also the second most frequent organism
      associated with avian infections. Currently, it is not known whether there is a
      link between the environmental isolates and/or human isolates of A. flavus and
      those responsible for aspergillosis in birds. Microsatellite typing was used to
      analyze 29 A. flavus clinical and environmental avian isolates and 63 human
      clinical isolates collected from patients with a variety of aspergillosis
      diseases. The combination of all six markers yielded 77 different genotypes with
      a 0.98 D value. A. flavus genotypes obtained from avian isolates were compared
      with those obtained from human clinical and environmental samples. The
      standardized indices of association I (A) and rBarD were significantly different
      from zero (p < 0.01), suggesting a prevailing clonal reproduction. There was high
      genetic diversity between the hospital and poultry environments of A. flavus
      isolates. The human environmental population was significantly differentiated
      from environmental and clinical avian populations (F (st) > 0.25). The avian
      clinical subpopulation exchanged few strains with the environmental human (N (m)
      = 7.24) and avian (N (m) = 6.60) populations. The minimum spanning tree analysis
      identified three A. flavus genotype clusters that were highly structured
      according to the isolation source (p < 10(-4)).

PMID- 22956011
TI  - Prevention of sudden cardiac death in patients with chronic kidney disease: risk
      and benefits of the implantable cardioverter defibrillator.
AB  - Implantation of implantable cardioverter defibrillators (ICDs) for primary
      prevention has been shown to significantly reduce mortality in several randomized
      controlled trials. However, many of these trials have excluded patients on
      hemodialysis as well as patients with advanced chronic kidney disease (CKD).
      Whether the benefits of ICD therapy extend to patients with CKD is not clear.
      This review will examine the relationship between advancing stage of CKD and
      risk/benefit of ICD placement. Furthermore, we will review the recent evidence
      for the rates of complications as CKD advances. The intent is to assist the
      clinician who is considering the risks and benefits of ICD implantation in
      patients who have significant competing comorbidities and have not been
      specifically studied in randomized controlled trials.

PMID- 22956012
TI  - TAPP or TEP? Population-based analysis of prospective data on 4,552 patients
      undergoing endoscopic inguinal hernia repair.
AB  - BACKGROUND: Whether total extraperitoneal inguinal hernia repair (TEP) is
      associated with worse outcomes than transabdominal preperitoneal inguinal hernia
      repair (TAPP) continues to be a matter of debate. The objective of this large
      cohort study is to compare outcomes between patients undergoing TEP or TAPP.
      METHODS: Based on prospective data of the Swiss association of laparoscopic and
      thoracoscopic surgery, all patients undergoing unilateral TEP or TAPP between
      1995 and 2006 were included. The following outcomes were compared: conversion
      rates, intraoperative and postoperative complications, duration of operation.
      RESULTS: Data on 4,552 patients undergoing TEP (n=3,457) and TAPP (n=1,095) were
      collected prospectively. Average age and American Society of Anesthesiologists
      score were similar in the two groups. Patients undergoing TEP had a significantly
      higher rate of intraoperative complications (TEP 1.9% vs. TAPP 0.9%, p=0.029) and
      surgical postoperative complications (TEP: 2.3% vs. TAPP: 0.8%, p=0.003). The
      postoperative length of stay was longer for patients undergoing TAPP (2.9 vs. 2.3
      days, p=0.002), whereas the duration of the operation was longer for TEP (66.6
      vs. 59.0 min, p<0.001) and the conversion rate was higher (TEP 1.0% vs. TAPP
      0.2%, p=0.011). CONCLUSIONS: This study is one of the first population-based
      analyses comparing TEP and TAPP in a prospective cohort of more than 4,500
      patients. Intraoperative and surgical postoperative complications were
      significantly higher in patients undergoing TEP. TEP is also associated with
      longer operating times and higher conversion rates. Therefore, on a population
      based level, the TAPP technique appears to be superior to the TEP repair in
      patients undergoing unilateral inguinal hernia repair.

PMID- 22956013
TI  - Collaboration in surgical capacity development: a report of the inaugural meeting
      of the Strengthening Rwanda Surgery initiative.
AB  - BACKGROUND: Increasing access to surgical care is among the prioritized
      healthcare initiatives in Rwanda and other low income countries, where only 3.5 %
      of surgical procedures worldwide are being performed. Partnerships among surgeons
      at academic medical centers, non-governmental organizations, and representatives
      of industry for building sustainable local surgical capacity in developing
      settings should be explored. METHODS: With the goal of improving collaboration
      and coordination among the many stakeholders in Rwandan surgery, the Rwanda
      Surgical Society (RSS) convened a participatory workshop of these groups in
      Kigali in March 2011. The meeting consisted of presentations from Rwandan
      surgical leaders and focused brainstorming sessions on collaborative methods for
      surgical capacity building. RESULTS: The outcome of the meeting was a set of
      recommendations to the Rwandan Ministry of Health (MOH) and the formation of an
      ad hoc team, the Strengthening Rwanda Surgery (SRS) Advising Group. The inaugural
      meeting of the advising group served to establish common goals, a framework for
      ongoing communication and collaboration, and commitment to a fully Rwandan agenda
      for surgical and anesthesia capacity development. The SRS Advising Group
      continues to meet and collaborate on training initiatives and has been integrated
      into the MOH plan to scale up human resources across disciplines. CONCLUSIONS:
      The SRS Initiative serves as an example of the concept of early communication and
      international collaboration in global surgical and anesthesia capacity building
      partnerships.

PMID- 22956015
TI  - Small liver remnants are more vulnerable to ischemia/reperfusion injury after
      extended hepatectomies: a case-control study.
AB  - BACKGROUND: There is evidence that small-for-size liver grafts are more
      vulnerable to ischemia/reperfusion injury after liver transplantation. We
      hypothesized that ischemic injury is more pronounced in small liver remnants
      after major hepatectomies. METHODS: Fifteen patients underwent extended
      hepatectomy with remnant liver mass less than 30% of standard liver weight (study
      group). These patients were matched with patients who underwent minor liver
      resection, with liver remnants equal to or more than 70% of standard liver weight
      (control group). Ischemia/reperfusion injury was assessed by tissue caspase-3
      activity postoperatively as well as peak aspartate aminotransferase (AST) values
      and a-glutathione S-transferase (alpha-GST) levels adjusted for remnant liver
      weight. In addition, caspase-3 activity and adjusted serum markers of hepatocyte
      injury were correlated with the degree of postoperative portal hypertension.
      RESULTS: Caspase-3 activity was higher in patients with small liver remnants
      (22.66+/-6.57 vs. 12.60+/-4.06 count per high-power field, p<0.001). Serum
      markers of hepatocyte injury, when adjusted per gram of liver remnant, were found
      to be higher in the study group than in the control group (AST: 1.26+/-0.25 vs.
      0.54+/-0.11 IU g(-1), p<0.001; alpha-GST: 0.14+/-0.02 vs. 0.08+/-0.01 IU g(-1),
      p<0.001). Tissue caspase-3 expression in the small liver remnant group correlated
      with both AST and alpha-GST levels adjusted per gram of liver remnant (r2=0.51,
      p=0.005 and r2=0.71, p<0.001, respectively). Significant correlations between
      postoperative portal hypertension and the same markers as well as caspase-3
      activity were also demonstrated. CONCLUSION: Liver remnants less than 30% of
      standard liver weight are much more susceptible to ischemia/reperfusion injury
      than controls twice the size. Adjustment of serum markers of hepatocyte injury to
      the liver remnant weight depicts injury more accurately.

PMID- 22956017
TI  - Ivano Bertini (1940-2012).

PMID- 22956016
TI  - Analgesic efficacy of bilateral superficial cervical plexus block in robot
      assisted endoscopic thyroidectomy using a transaxillary approach.
AB  - BACKGROUND: Nerve blocks and infiltration with local anesthetics are commonly
      employed methods for postoperative pain control. This prospective, randomized
      trial was conducted to determine whether bilateral superficial cervical plexus
      block (BSCPB) is effective for reducing acute postoperative pain after robot
      assisted endoscopic thyroidectomy (RAET) and to compare its effects with that of
      local wound infiltration (LWI). METHODS: Ninety-seven patients who were to
      undergo RAET were randomly assigned to one of three groups to receive BSCPB with
      either 20 mL of 0.525% ropivacaine (BSCPB group, n=32) or 20 mL of isotonic
      sodium chloride solution (Control group, n=32) or LWI with 20 mL of 0.525%
      ropivacaine (LWI group, n=33). Postoperative pain scores were assessed at the
      postoperative anesthesia care unit (PACU) and at 6, 24, and 48 h postoperatively
      using a visual analog scale (VAS). Patients with VAS scores of >=40 were
      administered rescue analgesics according to a standardized protocol. The main
      outcome variables were pain scores during the first postoperative 24 h and the
      number of patients requiring postoperative analgesic rescue. RESULTS: The BSCBP
      and LWI groups showed lower pain scores compared with the Control group at the
      PACU. The BSCPB group continued to show significantly lower pain scores compared
      with the LWI and Control groups at postoperative 6 and 24 h. The number of
      patients requiring analgesic rescue at the PACU was lower in the BSCPB and LWI
      groups than in the Control group. The number of patients requiring additional
      rescue analgesics after discharge from the PACU until the first 24 postoperative
      h was lower in the BSCPB group than in the LWI group. CONCLUSIONS: BSCPB and LWI
      are effective for reducing pain scores and analgesic requirements during the
      immediate postoperative period in patients who undergo RAET, with BSCPB being
      superior to LWI at postoperative 6-24 h.

PMID- 22956014
TI  - Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery
      After Surgery (ERAS(r)) Society recommendations.

PMID- 22956018
TI  - The identification of global patterns and unique signatures of proteins across 14
      environments using outer membrane proteomics of bacteria.
AB  - We test the hypothesis that organisms sourced from different environments exhibit
      unique fingerprints in macromolecular composition. Experimentally, we followed
      proteomic changes with 14 different sub-lethal environmental stimuli in
      Escherichia coli at controlled growth rates. The focus was on the outer membrane
      sub-proteome, which is known to be extremely sensitive to environmental controls.
      The analyses surprisingly revealed that pairs of proteins belonging to very
      different regulons, such as Slp and OmpX or FadL and OmpF, have the closest
      patterns of change with the 14 conditions. Fe-limited and cold-cultured bacteria
      have the most distinct global patterns of spot changes, but the patterns with
      fast growth and oxygen limitation are the closest amongst the 14 environments.
      These unexpected but statistically robust results suggest that we have an
      incomplete picture of bacterial regulation across different stress responses;
      baseline choices and growth-rate influences are probably underestimated factors
      in such systems-level analysis. In terms of our aim of getting a unique profile
      for each of the 14 investigated environments, we find that it is unnecessary to
      compare all the proteins in a proteome and that a panel of five proteins is
      sufficient for identification of environmental fingerprints. This demonstrates
      the future feasibility of tracing the history of contaminating bacteria in
      hospitals, foods or industrial settings as well as for released organisms and
      biosecurity purposes.

PMID- 22956019
TI  - Highly enantioselective synthesis of warfarin and its analogs catalysed by
      primary amine-phosphinamide bifunctional catalysts.
AB  - An efficient enantioselective Michael addition of 4-hydroxycoumarin to alpha,beta
      unsaturated ketones catalysed by primary amine-phosphinamide bifunctional
      catalysts has been developed. This reaction afforded Warfarin and its analogs in
      moderate to excellent yields (up to 99%) and good to excellent
      enantioselectivities (up to 99% ee).

PMID- 22956020
TI  - Grassroots origins, national engagement: exploring the professionalization of
      practicing healthcare ethicists in Canada.
AB  - Canadian ethicists have a long legacy of leadership in advocating for standards
      and quality in healthcare ethics. Continuing this tradition, a grassroots
      organization of practicing healthcare ethicists (PHEs) concerned about the lack
      of standardization in the field recently formed to explore potential options
      related to professionalization. This group calls itself "practicing healthcare
      ethicists exploring professionalization" (PHEEP). This paper provides a
      description of the process by which PHEEP has begun to engage the Canadian PHE
      community in the development of practice standards and related projects. By
      making our process and its ethical and cultural underpinnings transparent, we
      hope to prompt PHEs around the world to reflect on the importance of context,
      process and principles (not just outcomes) in the exploration of and possible
      movement towards professionalization. By sharing some of our key successes and
      challenges, we also hope to inspire our colleagues to recognize the value in
      developing practice standards and to contribute to this endeavor.

PMID- 22956021
TI  - Rhabdomyoma operation-intraoperative video of a very rare tumor entity.

PMID- 22956022
TI  - Right ventricular regional and global systolic function is diminished in patients
      with pulmonary arterial hypertension: a 2-dimensional ultrasound speckle tracking
      echocardiography study.
AB  - The purpose of the study is to evaluate right ventricular (RV) regional and
      global systolic function in patients with pulmonary arterial hypertension (PAH)
      by 2-dimensional ultrasound speckle tracking echocardiography (STE) and explore
      the impact of pulmonary artery systolic pressure (PASP) and pulmonary vascular
      resistance (PVR) on RV systolic function. 42 patients with PAH and 31 healthy
      controls were included in this study. RV longitudinal peak systolic strain (LS)
      and strain rate (LSRs) were measured at the basal, mid and apical segments of the
      RV free wall and septum by STE. RV global longitudinal peak systolic strain (GLS)
      and strain rate (GLSRs) were also measured by STE. RV ejection fraction (EF) was
      determinated by cardiac magnetic resonance (CMR) imaging. LS and LSRs of RV 6
      segments were significantly reduced in patients with PAH compared with controls.
      RV GLS and GLSRs were lower in patients with varying degrees of PAH than
      controls. Furthermore, RV GLS were most altered in patients with severe PAH
      compared with mild PAH. PVR was correlated with RV GLS and GLSRs (r1 = -0.549; r2
      = -0.466, respectively, P < 0.05). Similarly, there was correlation between PASP
      and RV GLS and GLSRs (r1 = -0.551; r2 = -0.425, respectively, P < 0.05). GLS and
      GLSRs were correlated with CMR-derived RVEF. (r1 = 0.693; r2 = 0.560,
      respectively, P < 0.05). STE can identify impaired RV regional and global
      systolic function in patients with PAH. STE-derived strain and strain rate can be
      used as novel indices for RV function assessment from 2-dimensional
      echocardiographic images.

PMID- 22956025
TI  - The role of feedback in morphological computation with compliant bodies.
AB  - The generation of robust periodic movements of complex nonlinear robotic systems
      is inherently difficult, especially, if parts of the robots are compliant. It has
      previously been proposed that complex nonlinear features of a robot, similarly as
      in biological organisms, might possibly facilitate its control. This bold
      hypothesis, commonly referred to as morphological computation, has recently
      received some theoretical support by Hauser et al. (Biol Cybern 105:355-370, doi:
      10.1007/s00422-012-0471-0 , 2012). We show in this article that this theoretical
      support can be extended to cover not only the case of fading memory responses to
      external signals, but also the essential case of autonomous generation of
      adaptive periodic patterns, as, e.g., needed for locomotion. The theory predicts
      that feedback into the morphological computing system is necessary and sufficient
      for such tasks, for which a fading memory is insufficient. We demonstrate the
      viability of this theoretical analysis through computer simulations of complex
      nonlinear mass-spring systems that are trained to generate a large diversity of
      periodic movements by adapting the weights of a simple linear feedback device.
      Hence, the results of this article substantially enlarge the theoretically
      tractable application domain of morphological computation in robotics, and also
      provide new paradigms for understanding control principles of biological
      organisms.

PMID- 22956024
TI  - Manufacture of Cheddar cheese using probiotic Lactobacillus plantarum K25 and its
      cholesterol-lowering effects in a mice model.
AB  - The probiotic adjunct Lactobacillus plantarum K25 was inoculated into milk to
      produce probiotic cheese. The effect of Lb. plantarum K25 on cheese composition,
      microbiological growth and survival during the manufacturing and ripening period,
      primary and secondary proteolysis during cheese ripening, and the in vivo
      cholesterol-lowering ability of the probiotic cheese were investigated. The
      results showed that the use of adjunct Lb. plantarum K25 in Cheddar cheese did
      not affect the cheese components including moisture, protein, fat, salt content
      and the pH value of cheese. During the whole ripening period, the probiotic
      adjunct maintained its viability, suggesting the effectiveness of Cheddar cheese
      as a vehicle for delivery of probiotic bacteria. No significant differences were
      observed in water-soluble nitrogen, 70 % ethanol-soluble nitrogen, 5 %
      phosphotungstic acid-soluble nitrogen, free amino acids and urea-PAGE patterns
      between the control and probiotic cheeses. Assessment of the in vivo cholesterol
      lowering property of cheese with Lb. plantarum K25 showed that the levels of
      serum total cholesterol, low-density lipoprotein cholesterol and triglycerides
      decreased significantly, and the level of serum high-density lipoprotein
      cholesterol increased in mice fed with the probiotic cheese. The results
      indicated the potential function as a dietary item of the probiotic cheese with
      Lb. plantarum K25 to reduce the risk of cardiovascular diseases.

PMID- 22956023
TI  - Prevalence and molecular epidemiology of acquired AmpC beta-lactamases and
      carbapenemases in Enterobacteriaceae isolates from 35 hospitals in Spain.
AB  - The purpose of this investigation was to determine the prevalence of plasmid
      mediated AmpC (pAmpC) and carbapenemases in Enterobacteriaceae collected from 35
      hospitals in Spain and to establish their epidemiological relationships. We
      conducted a prospective multi-centre study on pAmpC- or carbapenemase-producing
      Enterobacteriaceae isolates from clinical samples collected from February to July
      2009. The strains suspected to carry pAmpC were resistant or showed intermediate
      susceptibility to co-amoxiclav and second- or third-generation cephalosporins.
      Strains suspected to carry a carbapenemase were selected because they showed a
      minimum inhibitory concentration (MIC) to imipenem >1 mg/L. Polymerase chain
      reaction (PCR) and a sequencing strategy were used to characterise the enzymes.
      The clonal relationships between isolates was analysed by pulsed field gel
      electrophoresis (PFGE). Among 100,132 Enterobacteriaceae isolates collected,
      1,654 were compatible with the production of pAmpC or carbapenemases. We found a
      prevalence of 0.64 % of pAmpC (n = 635) and 0.04 % of carbapenemases (n = 43).
      The most prevalent pAmpC enzymes were CMY-type (78.3 %), DHA-type (19.5 %), ACC
      type (1.6 %) and FOX-type (0.6 %). The CMY-type was the most frequent in
      Escherichia coli and Proteus mirabilis species, whereas the DHA-type was mainly
      found in Klebsiella spp. The enzymes involved in carbapenem resistance were VIM
      1, IMP-22 and the new IMP-28. Nine new bla genes were described: bla (CMY-54),
      bla (CMY-55), bla (CMY-56), bla (CMY-57), bla (CMY-96), bla (DHA-6), bla (DHA-7),
      bla (FOX-8) and bla (IMP-28). The prevalence of pAmpC or carbapenemases found is
      not negligible. The CMY-types were the predominant pAmpC, whereas the VIM or IMP
      enzymes were the predominant carbapenemases. Furthermore, we observed a great
      genetic diversity among pAmpC-producing strains and a close clonal relationship
      between carbapenemase-producing strains.

PMID- 22956026
TI  - First polymorphisms in JY-1 gene in cattle (Bos taurus indicus) and their
      association with sexual precocity and growth traits.
AB  - Protein JY-1 is a bovine oocyte-specific protein that regulates granulosa cell
      function and is involved in early embryonic development, influencing the chance
      of pregnancy. This study investigated molecular markers for the JY-1 gene. Seven
      SNPs were identified in exon 3 of the gene. The positions of the SNPs in the exon
      and the respective substitutions are: 163 (T/C), 281 (T/C), 321 (T/C), 532 (T/C),
      652 (A/G), 679 (T/C), and 722 (G/C) (GenBank: JN592587 and JF262042.2). SNP 163
      is located in a coding region and causes a proline-to-leucine substitution. The
      other SNPs are located in the 3'UTR region. SNPs 163, 281, 321, and 679 were
      genotyped in 297 Nellore heifers and the haplotypes were constructed. The
      haplotypes of JY-1 were not correlated with the traits studied at 5 %.

PMID- 22956027
TI  - Metal concentrations in tissues of two fish species from Qeshm Island, Iran.
AB  - The purpose of this study was to determine the concentrations of metals, cadmium,
      chromium, lead and nickel in Liza vaigiensis and Johnius carutta, in order to:
      compare metal concentrations between two species with different gender, and to
      determine the significance between metal concentrations in the gill, liver and
      muscle. The highest mean concentrations of cadmium, chromium, lead and nickel in
      different tissues of these two fish species were found in the liver of L.
      vaigiensis at 0.68, 0.83, 0.37 and 1.42 MUg g(-1), respectively; while the lowest
      mean concentrations of cadmium, chromium, lead and nickel were observed in the
      muscle of J. carutta at 0.16, 0.16, 0.03 and 0.29 MUg g(-1), respectively. The
      results showed that the metal concentrations in both species were higher in the
      females than in the males (except chromium in gill and cadmium in muscle of J.
      carutta). Also, the results indicated that the metal concentrations were
      different among fish tissues (one-way ANOVA, p < 0.001), but there was no
      difference (except lead in gills of J. carutta) between sex (male vs. female).

PMID- 22956028
TI  - Neonatal onset atypical hemolytic uremic syndrome successfully treated with
      eculizumab.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is characterized by the
      triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal
      impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first
      choice therapy in patients with aHUS based on the belief of an underlying
      complement dysregulation. Alternatively, eculizumab, which targets complement 5,
      is used to block complement activation. CASE-DIAGNOSIS/TREATMENT: Sudden onset
      macroscopic hematuria, hypertension, and bruises over the entire body were noted
      in a 5 day-old newborn. Investigations revealed hemolytic anemia,
      thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis
      of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute
      kidney injury were initiated. This approach yielded full renal and hematological
      remission. The patient was discharged with FFP infusions, but subsequently
      developed three life-threatening disease recurrences at 1, 3, and 6 months of
      age. The last relapse presented with uncontrolled hypertension and impaired renal
      function while the patient was receiving FFP infusions. After the first dose of
      eculizumab, his renal and hematological parameters returned to normal and his
      blood pressure normalized. Genetic screening of the CFH gene revealed a novel
      homozygous p. Tyr1177Cys mutation. CONCLUSION: Eculizumab can be considered as an
      alternative to plasma therapy in the treatment of specific patients with aHUS,
      even in infants.

PMID- 22956030
TI  - [Diseases of the oral cavity].

PMID- 22956031
TI  - [Physiology of the oral cavity. Dermatologic aspects].
AB  - The oral cavity is the first part of the digestive tract and, thus, the natural
      entry of food and fluids into the body. Further, it is permanently colonized by
      bacteria as are all other body surfaces. Humans have two sets of teeth: the
      deciduous dentition with 20 teeth and the permanent dentition with 32 teeth. Our
      teeth are unique solid bodies which penetrate the lining surface of the mouth.
      Thus special defense mechanisms are required to prevent the invasion of
      microorganisms into connective tissue and bone through the gap between the tooth
      surface and the gingiva. The host response is observed clinically as inflammation
      (gingivitis). In the conflict of microbiological exposure and host response this
      defense mechanism will derail in some individuals early and in most individuals
      later in life. The host's line of defense will yield to the microorganisms and
      the body will destroy the connective tissue and bone of the periodontal
      structures as part of its struggle against bacteria. Halitosis may indicate a
      particular medical problem (e.g. periodontitis). Contrary to common belief, in
      most cases halitosis is not due to gastric problems but is caused primarily by
      bacteria of the oral cavity.

PMID- 22956032
TI  - [Clinical aspects and treatment of recurrent aphthous ulcers].
AB  - Recurrent aphthous ulcers are the most common inflammatory lesions of the oral
      mucosa, occurring in up to 10% of the population and even more common in
      children. The history, morphological characteristics, predilection sides and
      typical stages of aphthae help to distinguish them from other diseases that may
      exhibit aphthous-like lesions. Underlying diseases should be excluded. The main
      goals of therapy are to minimize pain and functional disabilities as well as
      decrease frequency and severity of recurrences. Topical symptomatic relief is the
      standard of care for simple cases of recurrent aphthosis. In cases of major
      aphthosis or systemic involvement, topical therapies are still useful but should
      be combined with systemic therapy, such as colchicine, pentoxifylline or
      prednisolone. In case of Adamantiades-Behcet disease, systemic immunomodulatory
      drugs can inhibit the development of new lesions. This overview summarizes
      morphological and presentation forms of aphthae, differential diagnoses and
      evidence-based therapeutic possibilities.

PMID- 22956033
TI  - [Pigmented lesions of the oral mucosa].
AB  - The oral mucosa contains melanocytes, even though one might not suspect this when
      examining white subjects. Drug-induced pigmentation is usually irregularly
      distributed over the oral mucosa; typical causes are contraceptives and
      tetracyclines. Localized traumatic pigmentation can be due to injuries
      contaminated by foreign material (dust). Not infrequently an amalgam tattoo can
      be seen, caused by introduction of amalgam during dental treatment with rotating
      instruments. Focal melanosis is harmless. Neoplastic pigmentation is rare.
      Melanotic nevi are small with indistinct borders. Malignant melanoma occurs
      predominantly on the maxilla or hard palate. Frequently it has already
      metastasized by the time of diagnosis. Verification by biopsy is essential if a
      lesion has suddenly appeared, is extensive, elevated, with irregular pigmentation
      and has no obvious cause.

PMID- 22956035
TI  - [PD-1 Antibodies. A new therapeutic option for metastatic malignant melanoma].

PMID- 22956036
TI  - [Dermatological conditions requiring intensive care].
AB  - Some skin conditions may require treatment in intensive care units. The early
      diagnosis of life-threatening dermatoses is a considerable challenge. We review
      skin diseases which may require intensive care. In addition to Stevens-Johnson
      syndrome and toxic epidermal necrolysis, representing adverse skin reactions, we
      discuss staphylococcal scalded skin syndrome and necrotizing fasciitis as
      infection-associated dermatoses, as well as angioedema. We focus on the course of
      disease describing clinical presentations, diagnostics and therapeutic strategies
      with respect to critical medical conditions.

PMID- 22956037
TI  - eta1-Allylpalladium complexes with a tridentate PNP ligand with different
      phosphino groups.
AB  - The iminodiphosphine 2-(PPh(2))C(6)H(4)-1-CH=NC(6)H(4)-2-(PPh(2)) (P-N-P') is
      used for the preparation of the complexes [Pd(eta(1)-CHR(1)-CH=CR(2)R(3))(P-N
      P')]BF(4) [R(1) = R(2) = R(3) = H: (1); R(1) = R(2) = Ph, R(3) = H: (2); R(1) =
      R(3) = H, R(2) = Ph: (3); R(1) = H, R(2) = R(3) = Me: (4)]. The P-N-P' tridentate
      coordination and the eta(1)-allyl bonding mode in the solid are confirmed by the
      X-ray structural analysis of 1. In solution, the complexes 1 and 2 undergo an
      eta(1)-eta(3)-eta(1) rearrangement at 298 K interconverting the bonding site of
      the allyl group. A five-coordinate structure with the phosphine ligands in the
      axial position is proposed for the eta(3)-allyl intermediate. For the dynamic
      process, a DeltaG(?) value of 53.8 kJ mol(-1) is obtained from (1)H NMR data of
      2. In 3 and 4, the allyl ligand is rigidly bound to the metal through the less
      substituted terminus, in line with the higher free energy content of the
      corresponding isomers: [Pd(eta(1)-CHPh-CH=CH(2))(P-N-P')](+) +48.78 kJ mol(-1);
      [Pd(eta(1)-CMe(2)-CH[double bond, length as m-dash]CH(2))(P-N-P')](+) +69.35 kJ
      mol(-1). The complexes react with secondary amines in the presence of
      fumaronitrile at different rates yielding allylamines and the palladium(0)
      derivative [Pd(eta(2)-fn)(P-N-P')] (5). On the basis of charge distribution on
      the allylic carbon atoms and of steric factors, the difference in rate and the
      regioselectivity in the amination of 1-3 are better rationalized by a mechanism
      with nucleophilic attack at the eta(3)-intermediate rather than by an S(N)2
      mechanism with nucleophilic attack at the Pd-CHR(1) carbon atom. The high
      regioselectivity in the reaction of 4 with piperidine implies an S(N)2' mechanism
      with nucleophilic attack at the CMe(2) allyl carbon. A dynamic process occurs
      also for the 18-electron complex 5 consisting in a dissociation-association
      equilibrium of the olefin.

PMID- 22956038
TI  - Foveal sparing in patients with Japanese Stargardt's disease and good visual
      acuity.
AB  - PURPOSE: Patients with Stargardt's disease usually have a poor visual prognosis.
      However, in our clinical practice we have observed some patients with dark-red
      foveal pigmentation (sparing) who had good best corrected visual acuity (BCVA)
      despite the presence of a late-stage disease. The purpose of this study was to
      investigate the BCVA outcomes in Japanese patients with Stargardt's disease with
      foveal sparing. METHODS: Eighteen consecutive patients (36 eyes) with Stargardt's
      disease underwent ophthalmoscopy, fluorescein angiography, fundus
      autofluorescence imaging, and near-infrared fundus autofluorescence (NIA)
      imaging. The patients were divided into two groups based on the presence or
      absence of foveal sparing. The presence of foveal sparing was determined based on
      ophthalmoscopy and NIA imaging results. The association between foveal sparing
      and BCVA was assessed statistically by Students' t test. RESULTS: Of the 36 eyes,
      ten (27.8 %) had dark-red foveal sparing. The mean BCVA of the group with sparing
      was 0.16 +/- 0.31, expressed in logarithm of the minimum angle of resolution
      (logMAR) units, and that of the group without sparing was 1.03 +/- 0.39 logMAR
      units, which is a significant difference (p = 0.0000002507). CONCLUSION: A
      subgroup of Japanese patients with late-stage Stargardt's disease and dark-red
      foveal sparing maintained a relatively good BCVA. The pigmentation was clearly
      observed using NIA and proved useful for assessing the BCVA prognosis.

PMID- 22956039
TI  - A novel approach to cancer treatment using structural hybrids of the p53 gene
      family.
AB  - The p53 tumor suppressor belongs to a gene family that includes two other
      structurally and functionally related members: p73 and p63. The regulation of p53
      activity differs significantly from that of p73 and p63. To enhance the tumor
      suppressive activity of p53, we constructed six recombinant adenoviruses that
      encode hybrid proteins with three functional domains derived from either p53 or
      TAp63gamma. The potency of these hybrid molecules in suppressing tumorigenesis
      was evaluated using in vitro and in vivo models. Of the hybrid molecules tested,
      one hybrid named p63-53O was the most potent activator of apoptosis in human
      cancer cells. The p63-53O hybrid is composed of the transcriptional activation
      domain and DNA-binding domain of TAp63gamma and the oligomerization domain of
      p53. The p63-53O hybrid efficiently transactivated p53AIP1. Moreover, silencing
      of p53AIP1 partially abolished the apoptotic response to p63-53O in human cancer
      cells. The p53-p63 hybrid molecule is a novel potent anti-proliferative agent for
      the treatment of cancer.

PMID- 22956040
TI  - Enhanced antitumor efficacy of telomerase-specific oncolytic adenovirus with
      valproic acid against human cancer cells.
AB  - Replication-selective oncolytic viruses are being developed for human cancer
      therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin),
      in which the human telomerase reverse transcriptase promoter element drives
      expression of E1A and E1B genes linked with an internal ribosome entry site. OBP
      301 can replicate in, and causes selective lysis of, human cancer cells. Valproic
      acid (VPA), which is an effective antiepileptic drug, is known to inhibit the
      histone deacetylase activities. We determined whether the antitumor effect of OBP
      301 could be enhanced by VPA in human lung cancer cells. In an in vitro cell
      viability assay, OBP-301 infection killed four human lung cancer cell lines,
      H1299, H1299-R5 (a subline of H1299 with a low level of the coxsackievirus and
      adenovirus receptor (CAR) expression), H460, and A549, more efficiently in the
      presence of VPA than in its absence. VPA treatment increased CAR expression in
      all the four lung cancer cells. Consistent with their CAR upregulation, the
      infection efficiency of adenoviruses in the presence of VPA was significantly
      higher than that in its absence. The molecular mechanism of this combined effect
      could be explained by an increase in adenovirus infectivity via VPA-mediated
      upregulation of CAR. These results suggest that treatment with OBP-301 in
      combination with VPA is a promising strategy for human lung cancer.

PMID- 22956041
TI  - Sindbis viral vectors target hematopoietic malignant cells.
AB  - Sindbis viral vectors target and inhibit the growth of various solid tumors in
      mouse models. However, their efficacy against blood cancer has not been well
      established. Here, we show that Sindbis vectors infect and efficiently trigger
      apoptosis in mouse BW5147 malignant hematopoietic T-cells, but only at low levels
      in human lymphoma and leukemia cells (Jurkat, Karpas, CEM, DHL and JB). The Mr
      37/67 kD laminin receptor (LAMR) has been suggested to be the receptor for
      Sindbis virus. However, JB cells, which are infected by Sindbis at low
      efficiency, express high levels of LAMR, revealing that additional factors are
      involved in Sindbis tropism. To test the infectivity and therapeutic efficacy of
      Sindbis vectors against malignant hematopoietic cells in vivo, we injected BW5147
      cells intraperitoneally into (C3HXAKR) F1 hybrid mice. We found that Sindbis
      vectors targeted the tumors and significantly prolonged survival of tumor-bearing
      mice. We also tested the Sindbis vectors in a transgenic CD4-Rgr model, which
      spontaneously develop thymic lymphomas. However, infectivity in this model was
      less efficient. Taken together, these results demonstrate that Sindbis vectors
      have the potential to target and kill hematopoietic malignancies in mice, but
      further research is needed to evaluate the mechanism underlining the
      susceptibility of human lymphoid malignancies to Sindbis therapy.

PMID- 22956042
TI  - Partial nephrectomy: is there an advantage of the self-retaining barbed suture in
      the perioperative period? A matched case-control comparison.
AB  - OBJECTIVE: To evaluate the efficacy of the self-retaining barbed suture (SRBS) in
      renal defect repair during partial nephrectomy (PN), by assessing perioperative
      outcomes. METHODS: From June 2010 on we have been using the SRBS for superficial
      layer closure during open and laparoscopic PN in two European centers. These data
      were collected prospectively and matched with historical PN cases performed with
      conventional suture. Cases were matched for PADUA score, surgical approach
      (laparoscopic or open) and the center where surgery was performed. Comparisons
      were made in patient characteristics and perioperative outcomes including warm
      ischemia time (WIT), changes in hemoglobin (Hb), changes in estimated glomerular
      filtration rate (eGFR) and perioperative complications between the SRBS and non
      SRBS groups. Statistical tests of significance were performed using Student's t
      test and chi-square test for continuous and categorical variables, respectively.
      RESULTS: Thirty-one consecutive cases of PN under WIT were performed with SRBS.
      These cases were matched with cases from the historical database of PN performed
      with conventional suture. The rate of perioperative complications was
      statistically significantly lower in the SRBS cohort (6.5 vs. 22.6 %, p = 0.038).
      Mean ischemia time was 19.6 min (SD, 7.5) in the SRBS group versus 21.8 min (SD,
      9.5) in the conventional suture group (p = 0.312). There were no significant
      differences between groups for postoperative changes in creatinine, eGFR and Hb.
      Limitations of this study include the absence of randomization and the relative
      small sample size. CONCLUSIONS: SRBS can be safely used during partial
      nephrectomy. SRBS reduces significantly the number of perioperative
      complications.

PMID- 22956043
TI  - Tissue-engineered fetal dermal matrices.
AB  - In the early to mid-gestation fetus, skin wounds heal with no scar formation and
      perfect restoration of dermal architecture. This phenomenon is intrinsic to fetal
      skin. The intrinsic phenotypic properties of the fetal fibroblast are believed to
      be "the effector of scarless repair". We sought to prepare dermal matrices with
      high similarity to the mid-gestation fetal dermis using the technology of "self
      assembly" with fetal dermal cells of 18, 20, and 22 wk gestation. Comparison of
      these dermal constructs to those prepared with neonatal dermal cells, adult skin,
      neonatal foreskin, and mid-gestation fetal skin demonstrates that these fetal
      dermal matrices bear marked morphological and biochemical resemblance to the mid
      gestation fetal dermis. In order to shed further light on the genes involved in
      scarless wound healing, we conducted a differential gene array analysis of the
      neonatal and fetal dermal matrices. Using a gene chip (GLYCOv4 gene chip) of
      approximately 1,260 human genes, we observed differential expression of 67 genes.
      A number of fibrotic genes were observed to be downregulated and anti-fibrotic
      genes upregulated.

PMID- 22956044
TI  - Flow cytometric determination of genome size for eight commercially important
      fish species in China.
AB  - The genome size (C value) of eight commercially important fish species in China
      was measured using flow cytometry. Chicken (Gallus domesticus) erythrocytes were
      used as reference cells. When using propidium iodide (PI) as the fluorescent dye,
      genome sizes were 1.09 +/- 0.08, 2.75 +/- 0.12, 1.05 +/- 0.05, 1.35 +/- 0.11,
      0.99 +/- 0.05, 0.90 +/- 0.08, 0.90 +/- 0.07, and 0.88 +/- 0.07 pg for Japanese
      eel (Anguilla japonica), mullet (Myxocyprinus asiaticus), yellowcheek carp
      (Elopichthys bambusa), blunt snout bream (Megalobrama amblycephala), yellow
      catfish (Pelteobagrus fulvidraco), ricefield eel (Monopterus albus), mandarin
      fish (Siniperca chuatsi), and snakehead (Ophicephalus argus), respectively.
      However, genome sizes were 1.25 +/- 0.00, 3.08 +/- 0.02, 1.25 +/- 0.00, 1.57 +/-
      0.01, 0.96 +/- 0.01, 1.00 +/- 0.01, 0.91 +/- 0.01, and 0.89 +/- 0.01 pg for these
      fishes, respectively, when 4', 6-diamidino-2-phenylindole (DAPI) was used as the
      fluorescent dye. Regardless of the dye used, the more evolutionarily advanced
      species had a smaller genome size than those with a lower evolutionary status.
      For each species, we also measured the size of erythrocytes and their nucleus and
      evaluated the relationships between erythrocyte size, nucleus size, chromosome
      number, and genome size. Genome size was positively correlated with erythrocyte
      nucleus size and chromosome number when using PI as the fluorescent dye, but it
      was only correlated with erythrocyte nucleus size when DAPI was used.

PMID- 22956045
TI  - Yttrium-90 radioembolization for unresectable standard-chemorefractory
      intrahepatic cholangiocarcinoma: survival, efficacy, and safety study.
AB  - PURPOSE: To assess the overall survival, efficacy, and safety of
      radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory
      intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable
      standard-chemorefractory ICC treated with Y90 were studied. Survival was
      calculated from the date of first Y90 procedure. Tumor response was assessed with
      the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed
      tomography or magnetic resonance imaging scans. National Cancer Institute Common
      Terminology Criteria (NCI CTCAE), version 3, were used for complications.
      Statistical analysis was performed by the Kaplan-Meier estimator by the log rank
      test. RESULTS: Nineteen patients underwent a total of 24 resin-based Y90
      treatments. Median survival from the time of diagnosis and first Y90 procedure
      was 752 +/- 193 [95 % confidence interval (CI) 374-1130] and 345 +/- 128 (95 % CI
      95-595) days, respectively. Median survival with Eastern Cooperative Oncology
      Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4)
      was 450 +/- 190 (95 % CI 78-822) and 345 +/- 227 (95 % CI 0-790) days,
      respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a
      median survival of 404 +/- 309 (95 % CI 0-1010) days versus 345 +/- 117 (95 % CI
      115-575) days for patients without metastasis (n = 8) (p = .491). No mortality
      was reported within 30 days from first Y90 radioembolization. One patient
      developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and
      transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients,
      respectively. CONCLUSION: Y90 radioembolization is effective for unresectable
      standard-chemorefractory ICC.

PMID- 22956046
TI  - Foot drop after ethanol embolization of calf vascular malformation: a lesson on
      nerve injury.
AB  - Ethanol is often used in sclerotherapy to treat vascular malformations. Nerve
      injury is a known complication of this procedure. However, the management of this
      complication is not well described in literature. This case describes a 10-year
      old boy with a slow flow vascular malformation in the right calf who underwent
      transarterial ethanol embolization following prior unsuccessful direct
      percutaneous sclerotherapy. The development of a dense foot drop that
      subsequently recovered is described, and the management of this uncommon but
      distressful complication is discussed. 

PMID- 22956047
TI  - Combat-related headache and traumatic brain injury.
AB  - Post-traumatic headache is a commonly described complication of traumatic brain
      injury. Recent studies highlight differences between headache features of combat
      veterans who suffered traumatic brain injury compared to civilians. Not
      surprisingly, there is a higher rate of associated PTSD and sleep disturbances
      among veterans. Factors of lower socioeconomic status, rank, and multiple head
      injuries appear to have a similar effect on post-traumatic headache in combat
      related traumatic brain injury. Areas of discordance in the literature include
      the effect of prolonged loss of consciousness and the prevalence of specific
      headache phenotypes following head trauma. To date, there have been no randomized
      trials of treatment for post-traumatic headache. This may be related to the
      variability of headache features and uncertainty of pathophysiologic mechanisms.
      Given this lack of data, many practitioners follow treatment guidelines for
      primary headaches. Additionally, because of mounting data linking PTSD to post
      traumatic headache in combat veterans, it may be crucial to choose multimodal
      agents and take a multidisciplinary approach to combat-related headache.

PMID- 22956048
TI  - Medium-term result of Elite Plus hip arthroplasty: the second modular evolution
      of the original Charnley low-friction arthroplasty.
AB  - BACKGROUND: The Elite Plus total hip arthroplasty (THA) system was introduced as
      the second modular evolution of the original Charnley low-friction arthroplasty.
      However, the results of the Elite Plus THA are currently considered to be
      inconsistent. The aim of this study was to clarify the medium-term results and
      the factors affecting the results of Elite Plus THA. METHODS: The results of 97
      Elite Plus THAs in 87 patients at 5 years or more postoperatively were reviewed.
      The patients' mean age was 65 years, and follow-up averaged 8.0 years. The Elite
      Plus stem was used in all hips, and three designs of socket, Hylamer Ogee in 40
      hips, Wroblewski Offset Bore in 38, and Charnley Ogee in 19, were implanted. The
      survival rates with loosening and revision as endpoints were analyzed. To clarify
      the risk factors affecting the survival rates, Charnley's functional
      classification, Bombelli's classification, Crowe's classification, structural
      bone grafting of the acetabulum, cup design, stem position, and grading of the
      cement mantle were evaluated. RESULTS:  CONCLUSIONS: The results of Elite Plus
      stem THA were excellent in the medium term. The cup design was a potential
      confounding factor for acetabular loosening, and the Hylamer Ogee socket was
      associated with a poor result.

PMID- 22956049
TI  - Pneumoperitoneum--the radiographic and clinical virtues of the supine abdominal
      film.

PMID- 22956051
TI  - Expulsion of selenium/protein nanoparticles through vesicle-like structures by
      Saccharomyces cerevisiae under microaerophilic environment.
AB  - Nano-selenium/protein is a kind of lower toxic supplement to human. Many
      microorganisms can reduce selenite/selenate to intracellular or extracellular
      selenium nanoparticles. This study examined the influence of dissolved oxygen on
      the expulsion of extracellular selenium/protein produced in Saccharomyces
      cerevisiae. More of the added selenite was reduced to extracellular selenium
      nanoparticles by yeast cells only under oxygen-limited condition than under
      aerobic or anaerobic condition. For the first time, we evidenced that
      selenium/protein nanoparticles synthesized in vivo were transported out of the
      cells by vesicle-like structures under microaerophilic environment. The
      characterizations of the extracellular spherical selenium/protein nanoparticles
      were also examined by SEM, TEM, EDX and FTIR.

PMID- 22956052
TI  - The effect of HMG-CoA reductase inhibitor on insulin resistance in patients
      undergoing peritoneal dialysis.
AB  - BACKGROUND: Insulin resistance is associated with the progression of
      atherosclerosis and is reported to predict cardiovascular mortality in patients
      with end-stage renal disease (ESRD). Although statins exert pleiotropic effects,
      it is uncertain whether statin therapy improves insulin resistance in these
      patients. In this prospective randomized controlled trial, we aimed to evaluate
      the effects of statin on insulin resistance among 70 patients undergoing
      peritoneal dialysis (PD). METHODS: Patients were randomized into a statin group
      (n = 35) or a control group (n = 35). The statin group received 10 mg per day of
      rosuvastatin for 6 months. We determined insulin resistance by homeostatic model
      assessment of insulin resistance (HOMA-IR) index. Serum concentrations of
      adipokines such as adiponectin, leptin, and resistin were measured using enzyme
      linked immunosorbent (ELISA) assay. As inflammatory markers, high sensitive C
      reactive protein (hsCRP) and interleukin-6 were also measured. RESULTS: There
      were no significant differences in baseline characteristics between the two
      groups. Compared to baseline value, statin treatment significantly decreased HOMA
      IR index from 2.37 +/- 1.08 to 2.05 +/- 0.82 (P = 0.014). There was a concordant
      decrease in hsCRP levels in the statin group (2.05 +/- 1.57 to 1.21 +/- 0.84
      mg/L, P < 0.001), but such improvements were not observed in the control group.
      When between-group differences in these parameters were compared, hsCRP levels
      were more decreased in the statin group than in the control group (P = 0.021 for
      between-group difference), whereas HOMA-IR index was not (P = 0.189 for between
      group difference). During this period, statin treatment did not result in the
      improved adipokine profiles. CONCLUSION: This study showed that statin therapy
      failed to improve insulin resistance in PD patients despite a significant decline
      in hsCRP levels after statin treatment. Our finding suggests that reducing
      inflammation by statin is of limited help to fully attenuate insulin resistance
      in these patients.

PMID- 22956053
TI  - Substantial changes in mastery perceptions of dementia caregivers with the
      placement of a care recipient.
AB  - OBJECTIVES: The current study examined how a key component of caregiving stress
      processes, global mastery perceptions, changes with placing the care recipient in
      a nursing home or institution. We also explored the role of primary stressors in
      accounting for mastery changes with placement and whether characteristics of the
      caregiver and care recipient moderate reactions to placement. METHOD: We applied
      multiphase growth curve models to prospective longitudinal data from 271
      caregivers in the Caregiver Stress and Coping Study who experienced placement of
      their care recipient. RESULTS: Using a time-to/from-placement metric, we found
      that caregivers typically experienced declines in mastery preceding placement,
      followed by a significant increase within 1 year after placement and further
      increases thereafter. Corresponding changes in primary stressors (role overload)
      mediated the placement-related increase in mastery. Caregivers who reported more
      depressive symptoms and activities of daily living/instrumental activities of
      daily living dependencies of the care recipient were more likely to experience
      larger placement-related increases in mastery perceptions. DISCUSSION: Our
      findings suggest that placement alters psychological resources of caregivers and
      this effect is driven by corresponding changes in primary stressors. Findings
      also underscore the importance of examining change processes across salient life
      events and transitions.

PMID- 22956054
TI  - Morphological risk factors of stroke during thoracic endovascular aortic repair.
AB  - PURPOSE: This study aims to identify independent factors correlating to an
      increased risk of perioperative stroke during thoracic endovascular aortic repair
      (TEVAR). METHODS: A prospective maintained TEVAR database, medical records, and
      imaging studies of 300 patients (205 men; median age of all, 66 years, range 21
      89), who underwent TEVAR between March 1997 and February 2011, were reviewed.
      Preoperative CT data sets were reviewed by two experienced radiologists with
      focus on the atheroma burden in the aortic arch (grade I, normal, to grade V,
      ulcerated or pedunculated atheroma). Aortic arch geometry (arch types I-III) was
      documented. Further parameters included in the univariate analysis were age,
      gender, urgency of repair, duration of procedure, adenosine-induced cardiac
      arrest or rapid pacing, proximal landing zone, left subclavian artery (LSA)
      coverage, and number of stent grafts. Multivariate logistic regression analysis
      was performed to assess the independent correlations of potential risk factors.
      RESULTS: Atherosclerotic aneurysm was the most common pathology (44%). One
      hundred and fifty-four of our patients (51%) were treated under urgent or
      emergent conditions. Seventeen percent of all patients had significant arch
      atheroma (grade IV or V), and 43% had a steep type III aortic arch. The
      perioperative stroke was 4% (12 patients; median age, 73 years, range 31-78). Two
      strokes were lethal (0.7%). All strokes were classified as embolic based on
      imaging characteristics. In eight patients, strokes were located in the left
      cerebral hemisphere (seven of them in the anterior and one in the posterior
      circulation). Four stroke patients (one in the left posterior circulation)
      underwent LSA coverage without revascularization. Three stroke patients had
      severe arch atheroma grade V. Five patients suffering stroke were recognized to
      have a type III aortic arch. Strokes were equally distributed between zones 0-2
      vs. 3-4 (n = 6 each, 5 vs. 3.3%). The highest incidence was found in zone 1
      (11.4%). In univariate analysis, grade V arch atheroma (odds ratios (OR), 5.35;
      95% confidence intervals (CI), 1.00-25.87; P = 0.035) and zone 1 deployment (OR,
      5.03; 95% CI, 1.19-20.03; P = 0.021) were significantly associated with
      perioperative stroke. In multivariate analysis, both parameters were confirmed as
      independent significant risk factors for stroke during TEVAR. CONCLUSIONS: Stroke
      risk during TEVAR is directly associated with the atheroma burden of the aortic
      arch and the proximal landing zone. These factors should be considered during
      patient selection, planning, and implantation strategies of TEVAR.

PMID- 22956055
TI  - Towards "a natural history of data": evolving practices and epistemologies of
      data in paleontology, 1800-2000.
AB  - The fossil record is paleontology's great resource, telling us virtually
      everything we know about the past history of life. This record, which has been
      accumulating since the beginning of paleontology as a professional discipline in
      the early nineteenth century, is a collection of objects. The fossil record
      exists literally, in the specimen drawers where fossils are kept, and
      figuratively, in the illustrations and records of fossils compiled in
      paleontological atlases and compendia. However, as has become increasingly clear
      since the later twentieth century, the fossil record is also a record of data.
      Paleontologists now routinely abstract information from the physical fossil
      record to construct databases that serve as the basis for quantitative analysis
      of patterns in the history of life. What is the significance of this distinction?
      While it is often assumed that the orientation towards treating the fossil record
      as a record of data is an innovation of the computer age, it turns out that
      nineteenth century paleontology was substantially "data driven." This paper
      traces the evolution of data practices and analyses in paleontology, primarily
      through examination of the compendia in which the fossil record has been recorded
      over the past 200 years. I argue that the transition towards conceptualizing the
      fossil record as a record of data began long before the emergence of the
      technologies associated with modern databases (such as digital computers and
      modern statistical methods). I will also argue that this history reveals how new
      forms of visual representation were associated with the transition from seeing
      the fossil record as a record of objects to one of data or information, which
      allowed paleontologists to make new visual arguments about their data. While
      these practices and techniques have become increasingly sophisticated in recent
      decades, I will show that their basic methodology was in place over a century
      ago, and that, in a sense, paleontology has always been a "data driven" science. 

PMID- 22956050
TI  - Brain resuscitation in the drowning victim.
AB  - Drowning is a leading cause of accidental death. Survivors may sustain severe
      neurologic morbidity. There is negligible research specific to brain injury in
      drowning making current clinical management non-specific to this disorder. This
      review represents an evidence-based consensus effort to provide recommendations
      for management and investigation of the drowning victim. Epidemiology, brain
      oriented prehospital and intensive care, therapeutic hypothermia,
      neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are
      addressed. When cardiac arrest is present, chest compressions with rescue
      breathing are recommended due to the asphyxial insult. In the comatose patient
      with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be
      avoided, hyperthermia treated, and induced hypothermia (32-34  degrees C)
      considered. Arterial hypotension/hypertension should be recognized and treated.
      Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and
      consider treating non-convulsive status epilepticus. Serial neurologic
      examinations should be provided. Brain imaging and serial biomarker measurement
      may aid prognostication. Continuous electroencephalography and N20 somatosensory
      evoked potential monitoring may be considered. Serial biomarker measurement
      (e.g., neuron specific enolase) may aid prognostication. There is insufficient
      evidence to recommend use of any specific brain-oriented neuroresuscitative
      pharmacologic therapy other than that required to restore and maintain normal
      physiology. Following initial stabilization, victims should be transferred to
      centers with expertise in age-specific post-resuscitation neurocritical care.
      Care should be documented, reviewed, and quality improvement assessment
      performed. Preclinical research should focus on models of asphyxial cardiac
      arrest. Clinical research should focus on improved cardiopulmonary resuscitation,
      re-oxygenation/reperfusion strategies, therapeutic hypothermia, neuroprotection,
      neurorehabilitation, and consideration of drowning in advances made in treatment
      of other central nervous system disorders.

PMID- 22956056
TI  - Quality by design approach: application of artificial intelligence techniques of
      tablets manufactured by direct compression.
AB  - The publication of the International Conference of Harmonization (ICH) Q8, Q9,
      and Q10 guidelines paved the way for the standardization of quality after the
      Food and Drug Administration issued current Good Manufacturing Practices
      guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline,
      offers a better scientific understanding of critical process and product
      qualities using knowledge obtained during the life cycle of a product. In this
      scope, the "knowledge space" is a summary of all process knowledge obtained
      during product development, and the "design space" is the area in which a product
      can be manufactured within acceptable limits. To create the spaces, artificial
      neural networks (ANNs) can be used to emphasize the multidimensional interactions
      of input variables and to closely bind these variables to a design space. This
      helps guide the experimental design process to include interactions among the
      input variables, along with modeling and optimization of pharmaceutical
      formulations. The objective of this study was to develop an integrated
      multivariate approach to obtain a quality product based on an understanding of
      the cause-effect relationships between formulation ingredients and product
      properties with ANNs and genetic programming on the ramipril tablets prepared by
      the direct compression method. In this study, the data are generated through the
      systematic application of the design of experiments (DoE) principles and
      optimization studies using artificial neural networks and neurofuzzy logic
      programs.

PMID- 22956057
TI  - Novel pH- and temperature-responsive blend hydrogel microspheres of sodium
      alginate and PNIPAAm-g-GG for controlled release of isoniazid.
AB  - This paper reports the preparation and characterization of novel pH- and thermo
      responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N
      isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by
      emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker.
      Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve
      encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was
      extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm
      the grafting reaction and chemical stability of INZ during the encapsulation.
      Differential scanning calorimetry was used to investigate the drug's physical
      state, while powder X-ray diffraction confirmed the molecular level dispersion of
      INZ in the matrix. Scanning electron microscopy confirmed varying surface
      morphologies of the drug-loaded microspheres. Temperature- and pH-responsive
      nature of the blend hydrogel microspheres were investigated by equilibrium
      swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4
      buffer media at 37 degrees C as well as at 25 degrees C. Kinetics of INZ release
      was analyzed by Ritger-Peppas empirical equation to compute the diffusional
      exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the
      release of INZ follows a diffusion swelling controlled release mechanism.

PMID- 22956058
TI  - Chronic toxicity of diphenhydramine hydrochloride to a freshwater mussel,
      Lampsilis siliquoidea, in a flow-through, continuous exposure test system.
AB  - Freshwater mussel populations are declining in North America. Potential
      anthropogenic stressors may be contributing to the declines and may include the
      continual presence of pharmaceutical compounds in waterways. Diphenhydramine
      hydrochloride (DH) is an over-the-counter antihistamine marketed under several
      name brand products including the common U.S. trademarked product, BenadrylTM.
      The toxicity of DH to freshwater mussels was assessed by initiating an
      unprecedented 28 day, continuous exposure trial with 1 day old mussels. Results
      indicated that the survival and growth of Lampsilis siliquoidea was not impacted
      by DH concentrations <=121 MUg/L after 28 days of continuous exposure. With the
      successful completion of this study, the techniques are now verified to evaluate
      the toxicity of waterborne compounds initiating 28-day chronic exposures with 1
      day old mussels.

PMID- 22956059
TI  - Mood and health-related quality of life among pediatric patients with heart
      failure.
AB  - Adult patients with heart failure (HF) commonly experience depression, with
      morbid and mortal consequences. However, mood disorders in pediatric patients
      with HF are poorly understood. This study examined mood and health-related
      quality of life (HRQOL) in children with HF and compared them cross-sectionally
      with those of healthy control subjects and heart transplant (Htx) recipients with
      good heart function. The 62 participants in this study were divided into three
      groups: HF subjects (n = 15), Htx subjects (n = 23), and healthy control subjects
      (n = 24). The HF subjects all had chronic HF with a left ventricular ejection
      fraction lower than 35 %. All the participants completed the Mini-Mental State
      Examination (MMSE), the Childhood Depression Inventory (CDI), and the Pediatric
      Quality-of-Life Inventory Cardiac Module (PedsQL CM). Overall, the MMSE scores
      and CDI subscale scores were similar for all the groups. The HF and Htx
      participants scored similarly on the PedsQL CM subscales for HRQOL, treatment
      anxiety, perceived physical appearance, cognitive function, and communication.
      However, the HF group had a significantly lower HRQOL related to heart problems
      and treatment than the Htx group. The prevalence of depression among children
      with HF is not as high as reported in the adult HF literature. However, certain
      aspects of HRQOL experienced by pediatric HF patients still suffer, especially
      those related to heart problems and treatment. Health-related QOL tended to be
      better for the Htx participants than for the HF participants. Exploring
      developmental and psychosocial outcomes is critical for patients with HF,
      especially because it has an impact on vital developmental, academic, and social
      outcomes.

PMID- 22956060
TI  - Effective radiation dose in computed tomographic angiography of the chest and
      diagnostic cardiac catheterization in pediatric patients.
AB  - Computed tomographic angiography (CTA) and cardiac catheterization are useful
      adjuncts to echocardiography for delineating cardiovascular anatomy in pediatric
      patients. These studies require ionizing radiation, and it is paramount to
      understand the amount of radiation pediatric patients receive when these tests
      are performed. Modern dosimetry methods facilitate the conversion of radiation
      doses of varying units into an effective radiation dose. To compare the effective
      radiation dose between nongated CTA of the chest and diagnostic cardiac
      catheterization in pediatric patients. This is a retrospective cohort study of
      patients of patients who underwent either nongated CTA of the chest or diagnostic
      cardiac catheterization between July 2009 and April 2010. Fifty patients were
      included in each group as consecutive samples at a single tertiary care center.
      An effective radiation dose (mSv) was formulated using conversion factors for
      each group. The median effective dose (ED) for the CTA group was 0.74 mSv
      compared with 10.8 mSv for the catheterization group (p < 0.0001). The median ED
      for children <1 year of age in the CTA group was 0.76 mSv compared with 13.4 mSv
      for the catheterization group (p < 0.0001). Nongated CTA of the chest exposes
      children to 15 times less radiation than diagnostic cardiac catheterization.
      Unless hemodynamic data are necessary, CTA of the chest should be considered in
      lieu of diagnostic cardiac catheterization in patients with known or presumed
      cardiac disease who need additional imaging beyond echocardiography.

PMID- 22956061
TI  - Dual-axis rotational coronary angiography: a new technique for detecting graft
      coronary vasculopathy in pediatric heart transplant recipients.
AB  - Annual surveillance coronary angiograpyhy to screen for graft coronary
      vasculopathy is routine practice after orthotopic heart transplantation.
      Traditionally, this is performed with direct coronary angiography using static
      single-plane or biplane angiography. Recently, technological advances have made
      it possible to perform dual-axis rotational coronary angiography (RA). This
      technique differs from standard static single-plane or biplane angiography in
      that a single detector is preprogrammed to swing through a complex 80 degrees 
      arc during a single injection. It has the advantage of providing a perspective of
      the vessels from a full arc of images rather than from one or two static images
      per contrast injection. The current study evaluated two coronary angiography
      techniques used consecutively at a single center to evaluate pediatric heart
      transplant recipients for graft coronary vasculopathy. A total of 23 patients
      underwent routine coronary angiography using both biplane static coronary
      angiography (BiP) and RA techniques at the Children's Hospital of Wisconsin from
      February 2009 to September 2010. Demographic and procedure data were collected
      from each procedure and analyzed for significance utilizing a Wilcoxon rank sum
      test. No significant demographic or procedural differences between the BiP and
      the RA procedures were noted. Specific measures of radiation dose including
      fluoroscopy time and dose area product were similar among the imaging techniques.
      The findings show that RA can be performed safely and reproducibly in pediatric
      heart transplant recipients. Compared with standard BiP, RA does not increase
      radiation exposure or contrast use and in our experience has provided superior
      angiographic imaging for the evaluation of graft coronary vasculopathy.

PMID- 22956062
TI  - Complete axillary lymph node dissection versus clinical follow-up in breast
      cancer patients with sentinel node micrometastasis: final results from the
      multicenter clinical trial AATRM 048/13/2000.
AB  - BACKGROUND: It has been suggested that selective sentinel node (SN) biopsy alone
      can be used to manage early breast cancer, but definite evidence to support this
      notion is lacking. The aim of this study was to investigate whether refraining
      from completion axillary lymph node dissection (ALND) suffices to produce the
      same prognostic information and disease control as proceeding with completion
      ALND in early breast cancer patients showing micrometastasis at SN biopsy.
      METHODS: This prospective, randomized clinical trial included patients with newly
      diagnosed early-stage breast cancer (T<3.5 cm, clinical N0, M0) who underwent
      surgical excision as primary treatment. All had micrometastatic SN. Patients were
      randomly assigned to one of the two study arms: complete ALND (control arm) or
      clinical follow-up (experimental arm). Median follow-up was 5 years, recurrence
      was assessed, and the primary end point was disease-free survival. RESULTS: From
      a total sample of 247 patients, 14 withdrew, leaving 112 in the control arm and
      121 in the experimental arm. In 15 control subjects (13%), completion ALND was
      positive, with a low tumor burden. Four patients experienced disease recurrence:
      1 (1%) of 108 control subjects and 3 (2.5%) of 119 experimental patients. There
      were no differences in disease-free survival (p=0.325) between arms and no cancer
      related deaths. CONCLUSIONS: Our results strongly suggest that in early breast
      cancer patients with SN micrometastasis, selective SN lymphadenectomy suffices to
      control locoregional and distant disease, with no significant effects on
      survival.

PMID- 22956063
TI  - miRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer.
AB  - BACKGROUND: MicroRNA (miRNA) has been shown the potential of cancer diagnosis. We
      investigated whether plasma miRNA expression could discriminate between patients
      with and without gastric cancer. METHODS: This study was divided into three
      steps: (1) miRNA microarray profiling on plasma samples from 20 gastric cancer
      patients and 20 healthy controls; (2) miRNA selection by real-time qRT-PCR on 30
      pairs of plasma from patients and controls; and (3) qRT-PCR validation on an
      independent set of plasma from 180 gastric cancer patients, 80 healthy controls,
      and 20 patients with gastric precancerous diseases. RESULTS: Of the 959 human
      miRNAs analyzed by microarray, 37 up-regulated miRNAs and seven down-regulated
      miRNAs were found in gastric cancer plasma. Of the seven discrepant miRNAs
      validated on the plasma from 30 gastric cancer patients and 30 healthy controls,
      both miRNA-199a-3p and miRNA-151-5p were significantly elevated (p < 0.05) and
      were significantly reduced after surgery (p < 0.05) in gastric cancer patients.
      Further large-scale validation showed that these two miRNAs expressions in plasma
      were significantly higher in gastric cancer patients than healthy controls and
      patients with gastric precancerous diseases, respectively. However, only the
      expression of miRNA-199a-3p in plasma was significantly associated with tumor
      invasion and with lymph node metastasis and tumor, node, metastasis stage. This
      marker yielded an area under the receiver operating characteristic curve area of
      0.837 with 80 % sensitivity and 74 % specificity in discriminating gastric cancer
      patients from healthy controls. In gastric cancer tissue, miRNA-199a-3p was
      expressed in the cytoplasm of tumor cells. CONCLUSIONS: miRNA-199a-3p in plasma
      could be a novel potential diagnostic biomarker for gastric cancer detection.

PMID- 22956064
TI  - Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary
      carcinoma differ from other periampullary malignancies?
AB  - BACKGROUND: Ampullary carcinomas typically have either intestinal or
      pancreatobiliary type of differentiation, histopathologically resembling
      carcinomas of its adjacent tissues (duodenum, bile duct, or pancreas). We
      evaluated whether the histologic type itself is more important for long-term
      survival than the fact that the tumor originated in the ampulla. METHODS:
      Microscopic slides from 207 consecutive pancreatoduodenectomies were reviewed (72
      pancreatic, 46 biliary, 61 ampullary, and 28 duodenal adenocarcinomas; 76
      intestinal type, 131 pancreatobiliary type). Tumor size, nodal involvement,
      margin involvement, degree of differentiation, vascular involvement, and
      perineural growth, as well as overall survival, were compared between different
      origins of the same histologic type. RESULTS: Intestinal-type ampullary
      adenocarcinomas had similar frequency of poor histopathologic factors compared to
      duodenal adenocarcinomas, and pancreatobiliary-type ampullary adenocarcinomas had
      similar frequency of poor histopathologic factors compared to pancreatobiliary
      type biliary and pancreatic adenocarcinomas. Adjusting for tumor size and nodal
      involvement, there was no difference in long-term survival between patients with
      intestinal-type ampullary, duodenal, or biliary and pancreatic tumors (p = 0.79),
      and there was no difference in long-term survival between patients with
      pancreatobiliary-type ampullary, biliary, or pancreatic tumors (p = 0.41).
      CONCLUSIONS: Long-term survival for patients with ampullary carcinomas equals
      pancreatic, biliary, and duodenal carcinomas when the same histologic type is
      compared. It can be questioned whether ampullary carcinomas should be regarded as
      a separate entity in classification of solid tumors. Clinical trials on adjuvant
      treatments for periampullary carcinomas should stratify by pancreatobiliary type
      versus intestinal type of histologic differentiation.

PMID- 22956065
TI  - What is the best definitive treatment for Graves' disease? A systematic review of
      the existing literature.
AB  - BACKGROUND: The management guidelines of the American Thyroid Association and
      American Association of Clinical Endocrinologists for Graves' disease (GD)
      include any of the following modalities: (131)I therapy, antithyroid medication,
      or thyroidectomy. No in-depth analysis has been performed comparing the treatment
      options, even though a single treatment option seems to be universally accepted.
      METHODS: A systematic review of the literature was performed to examine
      contemporary literature between 2001 and 2011 evaluating the management options
      of GD. We compiled retrospective and prospective studies analyzing surgery and
      radioactive iodine. Outcomes of interest included postoperative hypothyroidism,
      euthyroidism, and persistent or recurrent hyperthyroidism without
      supplementation. Success was defined as postoperative euthyroidism or
      hypothyroidism. Failure was defined as persistent or recurrent hyperthyroidism.
      RESULTS: Of the 14,245 patients, 4,546 underwent surgery [3,158 patients had
      subtotal thyroidectomy (STT) and 1,388 had total thyroidectomy (TT)] and 9,699
      had radioactive iodine. The radioactive iodine group consisted of 2,383 patients
      receiving 1-10 mCi, 1,558 patients receiving 11-15 mCi, 516 patients receiving
      >15 mCi, and 5,242 patients receiving an unspecified amount. Surgery was found to
      be 3.44 times more likely to be successful than radioactive iodine (p < 0.001).
      STT and TT were found to be 2.33 and 94.45 times more likely to be successful
      than radioactive iodine (p < 0.001), respectively. CONCLUSIONS: On the basis of
      the outcomes analyzed, surgery appears to be the most successful in the
      management of GD, with TT being the preferred surgical option.

PMID- 22956066
TI  - Ovarian metastasis is associated with retroperitoneal lymph node relapses in
      women treated for colorectal peritoneal carcinomatosis.
AB  - PURPOSE: To analyze the patterns of recurrence and the prognostic impact of
      ovarian metastases (OM) in a population of women with colorectal peritoneal
      carcinomatosis (CRPC) treated with curative intent. METHODS: Data from all
      consecutive women with CRPC who underwent curatively intended complete
      cytoreductive surgery (CRS) plus intraperitoneal chemotherapy at our institution
      were retrieved from a prospective database. A bilateral oophorectomy or a
      complementary unilateral oophorectomy was systematically performed during CRS.
      RESULTS: From 1994 to 2009, among 105 women who underwent CRS plus
      intraperitoneal chemotherapy for CRPC, 62 (60 %) had OM. Women with and without
      OM had comparable peritoneal cancer index (PCI) scores (10 vs. 12, respectively,
      p = 0.09). After a median follow-up of 60 (range 5-145) months, median overall
      survival of women with OM did not differ statistically from that of women without
      OM (respectively, 36 and 40 months; p = 0.75). Relapses occurred in 82 % of the
      patients, distributed similarly between the two groups except for retroperitoneal
      lymph node recurrence, which occurred in 19 patients (18 %), including 18 with
      OM. The only predictive factor for a retroperitoneal relapse was a history of OM
      (p = 0.0012). CONCLUSIONS: Retroperitoneal lymph node recurrence seems to be
      linked to OM originating from colorectal cancer and could worsen the prognosis. A
      systematic lymphadenectomy could be evaluated in women with isolated OM or very
      limited peritoneal carcinomatosis to analyze the incidence of invaded lymph nodes
      and study its potential benefit on survival.

PMID- 22956067
TI  - Postablation stimulated thyroglobulin level is an important predictor of
      biochemical complete remission after reoperative cervical neck dissection in
      persistent/recurrent papillary thyroid carcinoma.
AB  - BACKGROUND: The efficacy of reoperative cervical neck dissection (RND) in
      achieving biochemical complete remission (BCR) (or postreoperation stimulated
      thyroglobulin [sTg] of <0.5 ng/mL) remains unclear in persistent/recurrent
      papillary thyroid carcinoma (PTC). We hypothesized that lower postablation sTg
      levels would indicate a higher rate of BCR after RND. Our study examined the
      association between postablation sTg and BCR after one or more RNDs. METHODS: Of
      199 patients who underwent RND, 81 patients were eligible. The postablation sTg
      levels (<=2 and >2 ng/mL) were correlated with the postreoperation sTg levels
      after RNDs. Patients' clinicopathological characteristics, operative findings,
      and subsequent RNDs were compared between those with BCR after RNDs and those
      without. RESULTS: Those with postablation sTg levels of <=2 ng/mL had
      significantly higher BCR rate after the first RND (77.8 vs. 5.6 %, p < 0.001),
      overall BCR after one or more RNDs (77.8 vs. 9.3 %, p < 0.001), and better 5-year
      recurrence-free survival after the first RND (80.0 vs. 60.1 %, p = 0.049) than
      those with postablation sTg levels of >2 ng/mL. Overall BCR gradually decreased
      after each subsequent RND. Postablation sTg significantly correlated with
      postreoperation sTg (rho = 0.509, p < 0.001). After adjusting for the number of
      metastatic lymph nodes excised at first RND and presence of extranodal extension,
      postablation sTg of <= 0.2 ng/mL was the only independent factor for BCR after
      one or more RNDs (odds ratio 37.0, 95 % confidence interval 5.68-250.0, p =
      0.001). CONCLUSIONS: Only a third of patients who underwent one or more RNDs for
      persistent/recurrent PTC had BCR afterward. Postablation sTg level was an
      independent factor for BCR. Completeness of the initial operation is important
      for the subsequent success of RND.

PMID- 22956068
TI  - Microinvasive breast cancer: ER, PR, and HER-2/neu status and clinical outcomes
      after breast-conserving therapy or mastectomy.
AB  - BACKGROUND: Contemporary clinical outcomes of microinvasive breast cancer (MIBC),
      defined as no focus >1 mm, are not well characterized. We document the
      immunophenotype, incidence of axillary metastases, and rate of recurrence in a
      well-defined case series. METHODS: We reviewed 83 consecutive patients with MIBC
      from 1997 to 2005. Estrogen receptor (ER), progesterone receptor (PR), and human
      epidermal growth factor receptor 2 (HER-2/neu) receptor status were assessed. The
      cumulative incidence of local recurrence (LR) and nodal/distant recurrence was
      calculated. Predictors of recurrence were identified and effect estimates
      determined. RESULTS: Fifty-two patients (63%) underwent breast-conserving therapy
      (BCT) and 31 (37%) underwent mastectomy. Sixty-one percent had ER-positive
      disease and 49% had HER-2/neu-positive disease. Three (4%) of 68 patients with
      sentinel node mapping or axillary dissection had single node micrometastases, and
      none had macrometastases or multiple nodes involved. Median follow-up was 6.4
      years, with 6 LRs, 2 regional nodal recurrences, and 2 concurrent local/distant
      recurrences. The 5-year cumulative incidence of recurrence (local, nodal, or
      distant) was 5.3% (95% confidence interval [CI] 2.0-13.4) for all patients, and
      among BCT patients, the 5-year cumulative incidence of LR was 4.2% (95% CI 0.7
      12.7). HER-2/neu overexpression was not associated with recurrence (P = 0.46).
      Close/positive margins (<=2 mm) were significantly associated with an increased
      risk of LR after BCT or mastectomy (hazard ratio 8.8; 95% CI 1.6-48.8; P =
      0.003). CONCLUSIONS: MIBC has a favorable prognosis, and HER-2/neu
      overexpression, although highly prevalent, is not significantly associated with
      recurrence. Axillary metastases at diagnosis are small and infrequent. The
      cumulative incidence of LR after BCT is acceptable; however, our data confirm
      that negative margins (>2 mm) are required for optimal BCT outcomes.

PMID- 22956069
TI  - When is a lymph node dissection a lymph node dissection? The number of lymph
      nodes resected in sentinel and axillary lymph node dissections.
AB  - PURPOSE: We sought to compare the number of lymph nodes (LN) resected in axillary
      lymph node dissections (ALND) and sentinel lymph node dissections (SLND), and to
      assess the validity of registry reporting for axillary staging in breast cancer.
      METHODS: Women in the California Cancer Registry who underwent surgical axillary
      staging for T1/T2, M0 breast cancer between 2004 and 2008 were evaluated. The
      number of LN resected in patients reported as having SLND+ALND and ALND were
      assessed for compliance with 6 and 10 LN threshold definitions for ALND. The
      proportion of patients with <=3 LN removed was assessed for patients receiving
      SLND only. RESULTS: Of 71,907 patients, 45.5 % had SLND, 24.0 %, SLND+ALND, and
      30.5 %, ALND. The median number of LN resected with SLND cases was 2 (range 1
      41); SLND+ALND, 9 (range 1-63); and ALND, 11 (range 1-81) (p < 0.0001). Of
      patients undergoing ALND, 56.7 % had >=10 LN removed; 46.2 % of patients with
      SLND+ALND had >=10 LN removed (p < 0.0001). Overall, 75.5 % of patients with ALND
      had >=6 LN removed and 67.8 % of patients with SLND+ALND had >=6 LN removed (p <
      0.0001). Of those receiving only SLND, 83.4 % had <=3 LN removed. CONCLUSIONS: A
      significant proportion of patients did not meet the minimum LN count thresholds
      for full ALND or had excess LN removed in a SLND. Further investigation is
      required to determine whether absolute LN number or reported operative procedure
      and implied surgical technique better defines axillary staging in a registry
      database.

PMID- 22956070
TI  - Prognostic factor analysis in patients with metastatic spine disease depending on
      surgery and conservative treatment: review of 577 cases.
AB  - BACKGROUND: To date, skillful medical management and advanced surgical techniques
      have provided increased quality of life with less postoperative morbidity in
      patients with spinal metastasis. We assessed the survival of patients with spinal
      metastasis according to two treatment modalities: surgery and conservative
      treatment. METHODS: From 2005 to 2010, a total of 577 patients (200 surgery, 377
      conservative treatment) who had spinal metastasis were enrolled. Prognostic
      factors and survival were assessed by Cox regression and Kaplan-Meier analyses in
      patients receiving either surgery or conservative treatment. RESULTS: The mean
      age was 59.7 (range 21-87) years in the surgery group and 59.9 (range 28-90)
      years in the conservative treatment group. The major primary cancers were of
      lung, liver, and colorectal origin in the surgery group and lung, liver, and
      breast in the conservative group. The mean+/-SD Tokuhashi score in the surgery
      group was 8.12+/-3.09 and in the conservative group was 8.0+/-2.8 (not
      significant). The hazard ratio of the primary cancer group ranged from 1.870 to
      3.217 compared to that of the most favorable primary cancer group in all
      patients. Survival was affected significantly by sex, adjuvant therapy, and
      postoperative survival in the surgery group and by clinical symptom, metastasis
      to major internal organ, and primary cancer origin in the conservative group.
      CONCLUSIONS: With this retrospective review of 577 cases of spinal metastasis,
      different prognostic factors depending on the treatment modality were discovered.
      Hence, consideration of these factors depending on the treatment modality could
      be helpful in treating patients with spinal metastasis.

PMID- 22956071
TI  - Survival benefit of surgical treatment for hepatocellular carcinoma with inferior
      vena cava/right atrium tumor thrombus: results of a retrospective cohort study.
AB  - BACKGROUND: The significance of surgery in the treatment of hepatocellular
      carcinoma (HCC) extending into the inferior vena cava (IVC)/right atrium (RA) is
      currently unclear. We sought to clarify whether surgical treatment can improve
      survival in such patients. METHODS: A retrospective review was undertaken of
      patients with HCC and IVC/RA tumor thrombus who were potential candidates for
      surgery but who were finally treated surgically and nonsurgically between
      September 2000 and October 2010. The patients were subdivided according to
      therapeutic modalities, and the results for each group were compared. RESULTS: A
      total of 56 patients were included in this study. They were divided into three
      groups. Twenty-five patients underwent hepatectomy plus thrombectomy (surgical
      group), with minor morbidity and no mortality; the patients in this group had 1-,
      3-, and 5-year survival rates of 68.0, 22.5, and 13.5%, respectively, with a
      median survival of 19 months. Twenty patients were treated with transcatheter
      arterial chemoembolization, with 1- and 3-year survival rates of 15.0 and 5.0%,
      respectively (median survival 4.5 months). Eleven patients received symptomatic
      treatment only, and no one in this group survived longer than 1 year (median
      survival 5 months). The patients in surgical group survived significantly longer
      than the patients in the other two groups (p < 0.001). CONCLUSIONS: Although
      technically challenging, surgery for HCC with IVC/RA tumor thrombus can be safely
      performed and should be considered in patients with resectable primary tumor and
      sufficient hepatic reservoir because compared with transcatheter arterial
      chemoembolization or symptomatic treatment, it significantly improved patient
      survival.

PMID- 22956072
TI  - Effect of medial tibial torsion on the sagittal alignment of lower legs in
      patients with medial knee osteoarthritis.
AB  - PURPOSE: The fibular axis (FA) and anterior tibial cortex (ATC) are good
      determinants of the sagittal mechanical axis (MA) of lower legs during total knee
      arthroplasty (TKA).When compared with healthy subjects, a significant medial
      tibial torsion has been reported in patients with medial knee osteoarthritis;
      this should affect the alignment of lower legs. The purpose of this study was to
      clarify the effect of the medial torsion on relationship between sagittal MA and
      intraoperative references (FA and ATC). METHODS: Fifty knees of 50 patients with
      medial knee osteoarthritis who underwent primary TKA were included in this study.
      Using preoperative computed tomographic data, the tibial torsion angle was
      measured in the axial plane. The angle between FA and MA, and the angle between
      ATC and MA were also measured in the sagittal plane. RESULTS: The tibial torsion
      angle was 7.9 degrees  +/- 7.2 degrees  (range -11.3 degrees  to -24.3 degrees ).
      The angle between MA and FA was -1.8 degrees  +/- 0.8 degrees  (range -0.1
      degrees  to -4.3 degrees ), and the angle between MA and ATC was 4.6 degrees  +/-
      0.5 degrees  (range 3.1 degrees  to 5.5 degrees ). The population variance was
      significantly larger for the angle between MA and FA than that between MA and ATC
      (P = 0.0160). There was a significant positive correlation between the tibial
      torsion angle and the angle between MA and FA (R (2) = 0.5111, P < 0.0001).
      CONCLUSION: The angle between FA and MA in the sagittal plane increased in
      patients with large medial tibial torsion.

PMID- 22956073
TI  - [Structure and process quality of multimodal pain therapy. Results of a survey of
      pain therapy clinics].
AB  - Multimodal therapy has demonstrated good clinical effectiveness in the treatment
      of chronic pain syndromes. However, within the German health system a
      comprehensive and nationwide access to multimodal therapy is not available and
      further improvement is therefore necessary. In order to analyze the current
      status of multimodal therapy and specifically its structural and procedural
      requirements and qualities, a survey was carried out in 37 pain clinics with
      established multimodal treatment programs. An anonymous questionnaire was used
      for data collection. Results demonstrated that a substantial accordance was found
      between all pain clinics concerning requirements for space, facilities and staff.
      Structured multidisciplinary assessments were carried out by all pain clinics
      even though the amount of time allocated for this varied widely. The main focus
      of multimodal therapy in all facilities was based on a common philosophy with a
      cognitive-behavioral approach to reduce patient helplessness and avoidance
      behavior and to increase physical and psychosocial activities as well as to
      strengthen self-efficacy. Some differences in the ways and means to achieve these
      goals could be demonstrated in the various programs.

PMID- 22956074
TI  - [Glucocorticoids and androgens for treatment of tiredness and weakness in
      palliative care patients : a systematic review].
AB  - BACKGROUND: The therapy of tiredness, weakness and fatigue in palliative care
      patients is of growing interest. Glucocorticoids and androgens are habitually
      mentioned drugs for treatment. In this review evidence for glucocorticoids and
      androgens for these indications in palliative care patients are presented.
      MATERIALS AND METHODS: A systematic search of PubMed and Embase for studies on
      glucocorticoids and androgens for fatigue, asthenia, sedation, tiredness,
      weakness, exhaustion, cachexia, drowsiness and wasting in palliative care was
      carried out in August 2011. Furthermore, the Cochrane Library, references from
      the literature and leading textbooks were also searched. Study information was
      entered in a standardized extraction sheet. By a categorization of studies five
      endpoints were distinguished: fatigue, strength/weakness, tiredness, well
      being/quality of life and energy/activity/performance. RESULTS: A total of 11
      controlled studies with glucocorticoids and 13 controlled studies with androgens
      were included. In addition four uncontrolled studies, two case series and two
      surveys with glucocorticoids as well as six uncontrolled studies and one case
      series with androgen treatment were analyzed. All controlled trials of
      glucocorticoids were performed in cancer patients and all but one controlled
      trial of androgens in patients with HIV/AIDS. Glucocorticoids improved quality of
      life but results for changes of fatigue and weakness were inconsistent. Tiredness
      and energy were not improved. Androgens had a positive effect on fatigue and
      quality of life and showed variable effects on weakness. Androgens did not
      improve energy. Side effects were frequently documented but only rarely resulted
      in discontinuation of therapy. CONCLUSION: With the existing evidence no general
      recommendation for glucocorticoid and androgen use in tiredness and weakness in
      palliative care patients can be given; however, glucocorticoids in cancer
      patients and androgens in HIV positive-patients can be used in an individual
      trial for improving patient quality of life. The use in patients suffering from
      other disease entities should be evaluated in randomized controlled trials with a
      similar setting. The English full text version of this article will be available
      in SpringerLink as of November 2012 (under "Supplemental").

PMID- 22956075
TI  - [Recommendations for death rattle].
AB  - Noisy breathing during the terminal stages of life (death rattle) is one of the
      most common and most difficult symptoms to treat. In palliative medicine there
      are still no accepted guidelines for the treatment of death rattle in the final
      phase of life. In the first part of this article a description of death rattle is
      presented and in the second part a systematic literature review gives an insight
      into the effectiveness of interventions for death rattle. Two databases (Embase
      and Medline) were searched up to 2010 which identified 134 studies but only 6 met
      the inclusion criteria (2 cohort and 4 experimental studies) in which
      scopolamine, glycopyrrolate, butyl scopolamine, atropine and octreotide were
      tested. There is a lack of conclusive studies which investigated the
      effectiveness of treatment of death rattle. Furthermore, the identified studies
      revealed methodical problems. In general non-drug therapy is recommended as first
      choice. If anticholinergics are considered the selection also depends on whether
      simultaneous sedation is desired or not. The English full text version of this
      article will be available in SpringerLink as of November 2012 (under
      "Supplemental").

PMID- 22956076
TI  - [Methods and development of therapy recommendations for symptom control in
      palliative medicine].
AB  - The Drug Commission of the German Medical Association has decided to develop
      treatment guidelines for palliative care. A series of systematic reviews was
      commissioned to evaluate the evidence for interventions of common symptoms that
      burden patients and care givers. A common methodology for all reviews is
      described in this paper. The methodology was based on the work of the European
      Palliative Care Research Collaborative. Standardized search strategies were
      identified in PubMed and Embase and these templates were then adapted by the
      authors of the reviews according to their needs. The template included the target
      group (patients and disease entities), indications (symptoms) and interventions
      (medicines and classes of medicines). Target groups included search terms on
      palliative or hospice care, cancer, neurodegenerative diseases, HIV/AIDS as well
      as cardiac and pulmonary failure. The number of relevant hits was surveyed in the
      first 40 hits in some exemplary searches. This was used for fine tuning the
      search templates and to optimize the search strategy in order to achieve the
      highest possible yield with the minimum possible effort. The review series was
      performed using this search strategy. Every review graded the quality of the
      included evidence following categories of the Drug Commission of the German
      Medical Association. Based on these results and recommendations the treatment
      guidelines will be formulated which will offer concise and evidence-based
      guidelines for general palliative medicine, offering primary care givers guidance
      for adequate palliative care in severely ill and dying patients. The English full
      text version of this article will be available in SpringerLink as of November
      2012 (under "Supplemental").

PMID- 22956077
TI  - [Pharmacological therapy of refractory dyspnoea : a systematic literature
      review].
AB  - BACKGROUND: The management of breathlessness in patients with life-limiting
      diseases is still difficult and complex. This systematic review aims to summarize
      and analyze clinical trials of four different treatment options (opioids,
      benzodiazepines, corticosteroids and oxygen) for the relief of breathlessness.
      MATERIALS AND METHODS: A systematic review based on database searching of
      Medline, Embase and Cochrane Library was carried out and experts in the field
      were contacted. The search was conducted in July 2011. Included were systematic
      reviews, controlled and randomized controlled clinical trials in patients
      suffering from breathlessness due to advanced disease. Studies were selected,
      extracted and the data analyzed by two independent reviewers using narrative
      synthesis. RESULTS: The search retrieved 2,559 hits. Five systematic reviews and
      10 randomized controlled trials were included. Opioids (oral and parenteral) were
      the only drug group with evidence for relief of breathlessness. Benzodiazepines
      failed to show a significant effect for the relief of breathlessness intensity
      but demonstrated a tendency towards benefit. No studies were identified assessing
      steroids. There is no additional benefit from oxygen compared to room air in non
      hypoxemic cancer patients but there is a statistically significant benefit of
      oxygen in non-hypoxemic COPD patients. CONCLUSION: Oral and parenteral opioids
      seem to be effective for the relief of breathlessness and should be the first
      choice for pharmacological treatment. Benzodiazepines should be used with
      reservation. There is not enough evidence for the use of steroids except for COPD
      patients. Non-hypoxemic cancer patients do not benefit from oxygen. The English
      full text version of this article will be available in SpringerLink as of
      November 2012 (under "Supplemental").

PMID- 22956078
TI  - Effects of cell culture techniques on gene expression and cholesterol efflux in
      primary bovine mammary epithelial cells derived from milk and tissue.
AB  - Primary bovine mammary epithelial cells (pbMEC) are often used in cell culture to
      study metabolic and inflammatory processes in the udder of dairy cows. The most
      common source is udder tissue from biopsy or after slaughter. However, it is also
      possible to culture them from milk, which is non-invasive, repeatable and yields
      less contamination with fibroblasts. Generally, not much is known about the
      influence of cell origin and cell culture techniques such as cryopreservation on
      pbMEC functionality. Cells were extracted from milk and udder tissue to evaluate
      if milk-derived pbMEC are a suitable alternative to tissue-derived pbMEC and to
      test what influence cryopreservation has. The cells were cultivated for three
      passages and stored in liquid nitrogen. The relative gene expression of the five
      target genes kappa-casein, lingual antimicrobial peptide (LAP), lactoferrin,
      lysozyme (LYZ1) and the prolactin receptor normalised with keratin 8 showed a
      tendency to decrease in the tissue cultures, but not in the milk-derived
      cultures, suggesting a greater influence of the cultivation process on tissue
      derived cells, freezing lowered expression levels in both cultures. Overall
      expression of LAP and LYZ1 tended to be higher in milk cells. Cholesterol efflux
      was measured to compare passages one to seven in milk-derived cells. Passage
      number did not alter the efflux rate (p <= 0.05). We showed for the first time
      that the extraction of pbMEC from milk can be a suitable alternative to tissue
      extraction.

PMID- 22956080
TI  - Husbandry of Xenopus tropicalis.
AB  - Xenopus tropicalis combine the advantages of X. laevis, for example using
      explants and targeted gain of function, with the ability to take classical
      genetics approaches to answering cell and developmental biology questions making
      it arguably the most versatile of the model organisms. Against this background,
      husbandry of X. tropicalis is less well developed than for its larger, more
      robust relative. Here we describe the methods used to keep and breed these frogs
      successfully.

PMID- 22956081
TI  - Generating diploid embryos from Xenopus tropicalis.
AB  - A spectacular advantage of Xenopus tropicalis is the ease with which diploid
      embryos can be generated year round. By the simple administration of human
      chorionic gonadotropin, an investigator can generate many hundreds of
      synchronized embryos by in vitro fertilization or thousands of embryos from a
      mating pair. The ability to induce ovulations when desired facilitates many
      different experiments such as experimental embryology, molecular manipulation of
      gene products, and genetics.

PMID- 22956079
TI  - Xenopus tropicalis as a model organism for genetics and genomics: past, present,
      and future.
AB  - Xenopus tropicalis was introduced as a model system for genetic, and then genomic
      research, in the early 1990s, complementing work on the widely used model
      organism Xenopus laevis. Its shorter generation time and diploid genome has
      facilitated a number of experimental approaches. It has permitted
      multigenerational experiments (e.g., preparation of transgenic lines and
      generation of mutant lines) that have added powerful approaches for research by
      the Xenopus community. As a diploid animal, its simpler genome was sequenced
      before X. laevis, and has provided a highly valuable resource indispensable for
      all Xenopus researchers. As more sophisticated transgenic technologies for
      manipulating gene expression are developed, and mutations, particularly null
      mutations, are identified in widely studied genes involved in critical cellular
      and developmental processes, researchers will increasingly turn to X. tropicalis
      for definitive analysis of complex genetic pathways. This chapter describes the
      historical and conceptual development of X. tropicalis as a genetic and genomic
      model system for higher vertebrate development.

PMID- 22956082
TI  - Navigating the Xenopus tropicalis genome.
AB  - The frog Xenopus laevis has for more than 60 years served as a model system for
      the study of vertebrate embryogenesis, molecular and cell biology, and
      physiology. Recently, there has been great interest in the related species
      Xenopus tropicalis, in part because it is diploid, unlike the allotetraploid X.
      laevis, and therefore amenable to forward genetics, adding to the strengths of
      the frog system. The genome sequence of X. tropicalis was published in 2010 and
      this resource is facilitating rapid progress in applying transcriptomic, genomic,
      proteomic, and systems biological approaches for which the Xenopus system is well
      suited. However, the availability of the primary nucleotide sequence is only the
      first step in using the genome. Accessing information embedded in the genome
      sequence requires well-annotated genes and knowledge of how to navigate the data.
      The current chapter provides a step-by-step guide for the novice to finding genes
      of interest in the current genome assembly, supplemented with detailed notes to
      improve understanding. Several publically available internet-based tools for
      examining the X. tropicalis genome are discussed, with special emphasis placed on
      the examination of synteny. Accurate determination of gene identity is enhanced
      by examination of orthology relationships with other organisms and thus synteny
      is a powerful tool. This chapter provides an access path into the Xenopus genome
      to enhance the researchers' ability to manipulate the organism.

PMID- 22956084
TI  - Forward genetic screens in Xenopus using transposon-mediated insertional
      mutagenesis.
AB  - The class II DNA "cut-and-paste" transposons have been used to efficiently modify
      the Xenopus genome for transgenesis applications. Once integrated, the transposon
      is an effective substrate for excision and re-integration (remobilization)
      elsewhere in the genome by simply supplying the transposase enzyme in trans. We
      have used two methods to remobilize transposons resident in the frog genome:
      micro-injection of transposase mRNA at the one-cell stage and expression of the
      enzyme in the germline from a transgene. Double-transgenic frogs (hoppers) that
      harbor transgenes for both the substrate transposon and the transposase enzyme
      are outcrossed to wild-type animals and the progeny are scored for changes in
      reporter gene expression. Although both methods work effectively to remobilize
      transposons, the breeding-mediated strategy eliminates the time-consuming micro
      injection step; novel integration events are produced by simply outcrossing the
      hopper frogs. As each outcross of Xenopus tropicalis typically produces 2,000, or
      more, progeny, this method can be used to perform large-scale insertional
      mutagenesis screens in this highly tractable developmental model system.

PMID- 22956083
TI  - Genetic analysis of Xenopus tropicalis.
AB  - The pipid frog Xenopus tropicalis has emerged as a powerful new model system for
      combining genetic and genomic analysis of tetrapod development with robust
      embryological, molecular, and biochemical assays. Its early development closely
      resembles that of its well-understood relative X. laevis, from which techniques
      and reagents can be readily transferred. In contrast to the tetraploid X. laevis,
      X. tropicalis has a compact diploid genome with strong synteny to those of
      amniotes. Recently, advances in high-throughput sequencing together with solution
      hybridization whole-exome enrichment technology offer powerful strategies for
      cloning novel mutations as well as reverse genetic identification of sequence
      lesions in specific genes of interest. Further advantages include the wide range
      of functional and molecular assays available, the large number of embryos/meioses
      produced, and the ease of haploid genetics and gynogenesis. The addition of these
      genetic tools to X. tropicalis provides a uniquely flexible platform for analysis
      of gene function in vertebrate development.

PMID- 22956085
TI  - Targeted gene disruption with engineered zinc-finger nucleases (ZFNs).
AB  - Reverse genetics in Xenopus has been limited to knockdown strategies using
      antisense morpholino oligonucleotides (MOs). Recently, engineered zinc-finger
      nucleases have been used to induce targeted mutations resulting in null alleles.
      Zinc-finger nuclease (ZFN) technology has been adapted to induce null mutations
      in many systems previously refractory to targeted gene inactivation. Here we
      provide a general protocol for inducing targeted mutations in Xenopus tropicalis
      using ZFNs, a method to detect resulting mutations, and the steps to generate
      homozygous mutant embryos.

PMID- 22956086
TI  - Reverse genetic studies using antisense morpholino oligonucleotides.
AB  - Here we present a protocol, which allows loss-of-function studies in Xenopus
      embryos using antisense morpholino oligonucleotides (MOs). Gene knockdown studies
      provide a critical method for assessing gene function in vitro and in vivo. Such
      studies are currently performed in Xenopus using primarily one of the two main
      methods: (1) overexpression of dominant negative constructs or (2) inhibition of
      gene function by using MOs targeting either the initiation of translation or mRNA
      splicing. While a dominant negative approach is very effective, it often suffers
      from specificity. Given that MOs target very specific nucleotide sequences in the
      target RNA, it suffers considerably less from issues of specificity. The most
      convenient method for introducing MOs into embryos is through microinjection,
      which is a simple procedure. Therefore, a reverse genetics approach in Xenopus
      using MOs is an extremely powerful tool to study gene function, particularly when
      taking advantage of available sequence data in the post-genomic era. Furthermore,
      given the well-established fate map in Xenopus, it is also very easy to generate
      mosaic knockdown embryos, where the gene of interest is affected in defined
      regions of the embryo. Finally it should be noted that MOs can also be used to
      block miRNA function and processing, so that it provides a convenient method to
      not only perform gene knockdown studies on protein coding genes, but also
      noncoding genes. The protocol we describe here is for both Xenopus laevis and
      Xenopus tropicalis.

PMID- 22956087
TI  - Chemical genetics and drug discovery in Xenopus.
AB  - Chemical genetics uses small molecules to modulate protein function and has the
      potential to perturb any biochemical event in a complex cellular context. The
      application of chemical genetics to dissect biological processes has become an
      attractive alternative to mutagenesis screens due to its technical simplicity,
      inexpensive reagents, and low-startup costs. Xenopus embryos are particularly
      amenable to whole organism chemical genetic screens. Here we describe the basic
      protocols we have developed to screen small compound libraries on Xenopus laevis
      embryos. We score embryos either by observing phenotypic changes in the whole
      tadpole or by changes in gene expression pattern using automated wholemount in
      situ hybridization.

PMID- 22956088
TI  - Maternal mRNA knock-down studies: antisense experiments using the host-transfer
      technique in Xenopus laevis and Xenopus tropicalis.
AB  - The ability to inhibit the activity of maternally stored gene products in Xenopus
      has led to numerous insights into early developmental mechanisms. Oocytes can be
      cultured and manipulated in vitro and then implanted into the body cavity of a
      host female to make them competent for fertilization. Here, we summarize the
      methods for obtaining, culturing, and fertilizing Xenopus oocytes, with the goal
      of inhibiting maternal gene function through antisense oligonucleotide-mediated
      mRNA knock-down. We describe a simplified technique for implanting donor oocytes
      into host females using intraperitoneal injection. Also, we present optimized
      methods for performing the host-transfer procedure with Xenopus tropicalis
      oocytes.

PMID- 22956089
TI  - Generating transgenic frog embryos by restriction enzyme mediated integration
      (REMI).
AB  - Here we present a protocol for generating transgenic embryos in Xenopus laevis
      and Xenopus tropicalis. The method includes three steps: (1) The preparation of
      high-speed egg extracts, which facilitates the replacement of protamines in sperm
      nuclei with nucleosomes and decondenses the chromatin of sperm nuclei; (2) The
      isolation of sperm nuclei; and (3) The mixing of sperm nuclei, restriction
      enzyme, and high-speed extract in vitro, following by nuclear transplantation
      into unfertilized eggs to generate the transgenic embryos. This procedure
      generates non-mosaic transgenic embryos at high frequency and efficiency.

PMID- 22956090
TI  - A simple method of transgenesis using I-SceI meganuclease in Xenopus.
AB  - Here we present a protocol for generating transgenic embryos in Xenopus using I
      SceI meganuclease. This method relies on integration of DNA constructs,
      containing one or two I-SceI meganuclease sites. It is a simpler method than the
      REMI method of transgenesis, and it is ideally suited for generating transgenic
      lines in Xenopus laevis and Xenopus tropicalis. In addition to it being simpler
      than the REMI method, this protocol also results in single copy integration
      events rather than tandem concatemers. Although the protocol we describe is for
      X. tropicalis, the method can also be used to generate transgenic lines in X.
      laevis. We also describe a convenient method for designing and generating complex
      constructs for transgenesis, named pTransgenesis, based on the Multisite
      Gateway((r)) cloning, which include I-SceI sites and Tol2 elements to facilitate
      genome integration.

PMID- 22956091
TI  - Using PhiC31 integrase to mediate insertion of DNA in Xenopus embryos.
AB  - The two most common methods used to generate transgenic Xenopus embryos,
      restriction enzyme-mediated insertion, and I-SceI meganuclease take advantage of
      relatively common but spatially unpredictable double-stranded breaks in sperm,
      egg, or early embryo genomes. These methods also tend to insert multimeric copies
      of the transgene. An alternative is to use bacteriophage- or transposon-derived
      integrase or recombinase to mediate more site-specific insertion of the
      transgene. The use of phiC31 integrase requires a defined sequence for insertion
      and is compatible with insertion of a single copy of the transgene. We describe
      the protocol we use to facilitate phiC31 integrase transgene insertion including
      the use of insulator sequences to reduce position effect disruption of transgene
      activity.

PMID- 22956092
TI  - Xenopus transgenics: methods using transposons.
AB  - The generation of transgenic animals is an essential tool for many genetic
      strategies. DNA "cut-and-paste" transposon systems can be used to efficiently
      modify the Xenopus genome. The DNA transposon substrate, harbored on a
      circularized plasmid, is co-injected into fertilized Xenopus embryos at the one
      cell stage together with mRNA encoding the cognate transposase enzyme. The
      cellular machinery rapidly translates the exogenous mRNA to produce active
      transposase enzyme that catalyzes excision of the transposon substrate from the
      plasmid and stable integration into the genomic DNA.

PMID- 22956094
TI  - Tet-On binary systems for tissue-specific and inducible transgene expression.
AB  - Tissue-specific and inducible control of transgene expression is a cornerstone of
      modern studies in developmental biology. Even though such control of transgene
      expression has been accomplished in Xenopus, no general or widely available set
      of transgenic lines have been produced akin to those found in mouse and
      zebrafish. Here, I describe the design and characterization of transgenic lines
      in Xenopus constituting the Tet-On binary transgene expression system comprising
      two components: (1) rtTA transgenic lines, i.e., lines harboring the doxycycline-
      (Dox-) dependent transgenic transcription factor rtTA under control of a tissue
      specific promoter and (2) transgenic promoter (TRE) transgenic lines, i.e., lines
      harboring a gene of interest (hereafter called the transgene) under control of a
      promoter (TRE). In double transgenic animals, i.e., embryos or tadpoles harboring
      both the rtTA and TRE components, transgene expression remains off the absence of
      Dox. Addition of Dox to the rearing water causes a conformational change in rtTA
      allowing it to bind the TRE promoter and induce transgene expression. Tissue
      specificity of transgene expression is determined by the promoter regulating rtTA
      expression, and inducibility is determined by the addition of Dox to the rearing
      water. Deposition of rtTA and TRE transgenic lines enabling tissue-specific
      inducible control of transgene expression into the Xenopus stock center will
      provide a powerful and flexible resource for studies in developmental biology.

PMID- 22956093
TI  - Comparative genomics-based identification and analysis of cis-regulatory
      elements.
AB  - Identification of cis-regulatory elements, such as enhancers and promoters, is
      very important not only for analysis of gene regulatory networks but also as a
      tool for targeted gene expression experiments. In this chapter, we introduce an
      easy but reliable approach to predict enhancers of a gene of interest by
      comparing mammalian and Xenopus genome sequences, and to examine their activity
      using a co-transgenesis technique in Xenopus embryos. Since the bioinformatics
      analysis utilizes publically available web tools, bench biologists can easily
      perform it without any need for special computing capability. The co-transgenesis
      assay, which directly uses polymerase chain reaction products, quickly screens
      for the activity of the candidate elements in a cloning-free manner.

PMID- 22956095
TI  - Chromatin immunoprecipitation analysis of Xenopus embryos.
AB  - Chromatin immunoprecipitation (ChIP) is a powerful technique to study epigenetic
      regulation and transcription factor binding events in the nucleus. It is based on
      immune-affinity capture of epitopes that have been cross-linked to genomic DNA in
      vivo. A readout of the extent to which the epitope is associated with particular
      genomic regions can be obtained by quantitative PCR (ChIP-qPCR), microarray
      hybridization (ChIP-chip), or deep sequencing (ChIP-seq). ChIP can be used for
      molecular and quantitative analyses of histone modifications, transcription
      factors, and elongating RNA polymerase II at specific loci. It can also be
      applied to assess the cellular state of transcriptional activation or repression
      as a predictor of the cells' capabilities and potential. Another possibility is
      to employ ChIP to characterize genomes, as histone modifications and binding
      events occur at specific and highly characteristic genomic elements and
      locations. This chapter provides a step-by-step protocol of ChIP using early
      Xenopus embryos and discusses potential pitfalls and other issues relevant for
      successful probing of protein-genome interactions by ChIP-qPCR and ChIP-seq.

PMID- 22956096
TI  - Transcriptomics using next generation sequencing technologies.
AB  - Next generation sequencing technologies may now be applied to the study of
      transcriptomics. RNA-Seq or RNA sequencing employs high-throughput sequencing of
      complementary DNA fragments delivering a transcriptional profile. In this
      chapter, we aim to provide a starting point for Xenopus researchers planning on
      starting an RNA-Seq transcriptomics study. We begin by providing a section on
      template isolation and library preparation. The next section comprises the main
      bioinformatics procedures that need to be performed for raw data processing,
      normalization, and differential gene expression. Finally, we have included a
      section on studying deep sequencing results in Xenopus, which offers general
      guidance as to what can be done in this model.

PMID- 22956097
TI  - Databases of gene expression in Xenopus development.
AB  - Gene expression data for Xenopus are collected and curated in diverse forms and
      locations. The intention of this chapter is to give the reader a guide to the
      publicly accessible databases where these data can be found and an idea of the
      current scope and limitations of the data in these resources. Instructions are
      given on how to access and interpret the data provided by the NCBI Gene database,
      Xenbase, and the Xenopus full-length EST, quickImage, and Xenmark databases.

PMID- 22956098
TI  - Investigating alternative RNA splicing in Xenopus.
AB  - Alternative splicing, the process by which distinct mature mRNAs can be produced
      from a single primary transcript, is a key mechanism to increase the organism
      complexity. The generation of alternative splicing pattern is a means to expand
      the proteome diversity and also to control gene expression through the regulation
      of mRNA abundance. Alternative splicing is therefore particularly prevalent
      during development and accordingly numerous splicing events are regulated in a
      tissue or temporal manner. To study the roles of alternative splicing during
      developmental processes and decipher the molecular mechanisms that underlie
      temporal and spatial regulation, it is important to develop in vivo whole animal
      studies. In this chapter, we present the advantages of using the amphibian
      Xenopus as a fully in vivo model to study alternative splicing and we describe
      the experimental procedures that can be used with Xenopus laevis embryos and
      oocytes to define the cis-regulatory elements and identify the associated trans
      acting factors.

PMID- 22956099
TI  - Immunoisolation of protein complexes from Xenopus.
AB  - The immunoaffinity isolation of protein complexes is an essential technique for
      the purification and -concentration of protein complexes from cells and tissues.
      In this chapter we present the methodologies for the purification of proteins and
      protein complexes from Xenopus laevis and Xenopus tropicalis. Specific to this
      protocol are the techniques for the cryolysis of Xenopus cells and tissues, a
      procedure that limits contamination from yolk proteins while preserving
      endogenous protein complexes, the methodologies for immunoaffinity purification
      of proteins using magnetic beads, and the protocols for western blot analysis. In
      addition, the procedures in this chapter can be extended to use with proteomic
      analysis of protein complexes as presented in the following chapter.

PMID- 22956100
TI  - Complementary proteomic analysis of protein complexes.
AB  - Proteomic characterization of protein complexes leverages the versatile platform
      of liquid chromatography-tandem mass spectrometry to elucidate molecular and
      cellular signaling processes underlying the dynamic regulation of macromolecular
      assemblies. Here, we describe a complementary proteomic approach optimized for
      immunoisolated protein complexes. As the relative complexity, abundance, and
      physiochemical properties of proteins can vary significantly between samples, we
      have provided (1) complementary sample preparation workflows, (2) detailed steps
      for HPLC and mass spectrometric method development, and (3) a bioinformatic
      workflow that provides confident peptide/protein identification paired with
      unbiased functional gene ontology analysis. This protocol can also be extended
      for characterization of larger complexity samples from whole cell or tissue
      Xenopus proteomes.

PMID- 22956101
TI  - Antibody development and use in chromogenic and fluorescent immunostaining.
AB  - Antibody-based detection of protein distribution patterns both in wholemount and
      on sections revolutionized Xenopus research and ushered in the visual-based era
      of Xenopus data presentation. The ability to view the distribution of a gene
      product throughout an embryo makes it possible to rapidly map normal expression
      profiles and profiles that have been altered by an experimental intervention. The
      main limiting element in Xenopus immunostaining techniques has always been the
      availability of antibodies that work well on fixed whole embryos, a problem that
      persists. However, new antibodies are constantly being generated and improvements
      in detection systems allow antibodies that were once below the limits of
      detection to be utilized in multichannel immunofluorescence using tyramide
      amplification.

PMID- 22956102
TI  - Multicolor fluorescent in situ mRNA hybridization (FISH) on whole mounts and
      sections.
AB  - In situ hybridization involves the hybridization of an antisense RNA probe to an
      mRNA transcript and it is a powerful method for the characterization of gene
      expression in tissues, organs, or whole organisms. Performed as a whole mount
      (WISH), it allows the detection of mRNA transcripts in three dimensions, while
      combined with sectioning, either before or after hybridization, it provides gene
      expression information with cellular resolution. FISH relies on the fluorescence
      detection of probes and is the method of choice for the simultaneous detection of
      transcripts with similar or overlapping expression patterns, as each can be
      clearly distinguished by the selection of fluorophore. Here, we describe a
      protocol for performing multicolor FISH in Xenopus embryos in whole mounts and
      sections that can be further combined with antibody staining.

PMID- 22956103
TI  - Methods to analyze microRNA expression and function during Xenopus development.
AB  - microRNAs are a class of small noncoding RNAs that regulate gene expression at a
      posttranscriptional level. microRNAs are transcribed as primary transcripts,
      characterized by specific hairpin secondary structure that undergo stepwise
      processing to yield mature microRNAs of approximately 22 nt length. The function
      of the majority of vertebrate microRNAs has not yet been established and Xenopus
      offers a powerful system to test their biological function. Working with
      microRNAs is based on well-established protocols for the detection of mRNAs and
      manipulation of gene expression; however, the small size of mature microRNAs and
      their unique biogenesis require modifications to the existing protocols. Here, we
      present methods that can be used to detect, overexpress, and inhibit microRNAs in
      Xenopus tropicalis.

PMID- 22956104
TI  - A bromodeoxyuridine (BrdU) based protocol for characterizing proliferating
      progenitors in Xenopus embryos.
AB  - BrdU is a thymidine analog that is incorporated into DNA during the S-phase of
      the cell cycle. BrdU incorporation can be used to quantify the number of cells
      that are in S-phase in the time period that BrdU is available. Thus, BrdU
      incorporation is an essential method in the quantitative analysis of cell
      proliferation, during normal embryonic development or after experimental
      manipulation. It is a reliable and versatile method that can be easily combined
      with immunohistochemistry and in situ hybridization to relate cell proliferation
      with gene expression. BrdU incorporation has been used in all model organisms;
      here, we describe a protocol adapted for use in Xenopus embryos.

PMID- 22956105
TI  - Microscopy tools for quantifying developmental dynamics in Xenopus embryos.
AB  - Early Xenopus embryos, and embryonic tissues isolated from them, are excellent
      model systems to study morphogenesis. Cells migrate, change shape, and
      differentiate to form new tissues as embryos mature and recapitulate those same
      processes in tissue isolates. Both large-scale and small-scale cell and tissue
      movements can be visualized with a range of microscopy techniques. Furthermore,
      protein dynamics, fine-scale cell movements, and changes in cell morphology can
      be observed simultaneously as multicellular structures are sculpted. We provide
      an overview of complementary methods for visualizing macroscopic tissue
      movements, cell shape changes, and subcellular protein dynamics. Time-lapse
      imaging followed by quantitative image analysis aims to provide answers to some
      of the long-standing questions in developmental biology: How do tissues form? How
      do cells acquire specific shapes? How do proteins localize to specific positions?
      To address these questions we suggest strategies (1) to visualize whole embryos
      and tissue isolates using stereoscopes and epifluorescence imaging techniques,
      and (2) to visualize cell shapes and protein expression using high-resolution
      live imaging using confocal microscopy. These imaging approaches along with
      simple image analysis tools provide us with ways to understand the complex
      biology underlying morphogenesis.

PMID- 22956106
TI  - Mathematical modeling of gene regulatory networks in Xenopus development.
AB  - Mathematical modeling has become increasingly indispensable for scientists who
      study the dynamics of gene regulatory networks (GRN) that underlie cell
      differentiation and pattern formation in animal development including Xenopus
      embryogenesis. Here I outline a step-by-step procedure for constructing a
      mathematical model of GRN based on ordinary differential equations (ODE), using
      the network of Activin and its downstream target genes Xenopus Brachyury (Xbra)
      and Goosecoid (Gsc) as an example. I also briefly explain methods to analyse the
      dynamics described by an ODE model.

PMID- 22956107
TI  - Stem-cell-like embryonic explants to study cardiac development.
AB  - Cells from the animal pole of Xenopus blastula embryo possess pluripotency that
      can be used to generate various tissues and even functional organs ex vivo. This
      finding has sparkled development of a variety of experimental protocols to study
      mechanisms that underlie formation of various organs and explore strategies for
      organ engineering for clinical applications. In this chapter, key methods are
      described for using Xenopus stem-cell-like embryonic explants as an assay system
      for studying organ development, with a focus on cardiogenesis. This assay allows
      investigation of cardiogenesis in isolation from neighboring tissues, minimizes
      interference with other developmental processes, and presents the further
      advantage of a heterologous system to study cardiogenesis in isolation of
      endogenous development of the heart. The cardiogenic assays can be exploited to
      investigate molecular mechanisms and cellular processes that underlie function of
      different molecules involved in cardiogenesis.

PMID- 22956108
TI  - Studying regeneration in Xenopus.
AB  - For most Xenopus embryos, life is very short. The majority of research labs
      working with this model organism study the processes of early vertebrate
      patterning and morphogenesis. And quite rightly too, since over the last two
      decades labs across the world have provided the fate maps, animal cap assays,
      expression patterns, and functional screens that put Xenopus firmly on the map as
      a developmental model organism. Xenopus, however, still has a lot more to offer.
      A new wave of interest in later developmental events has followed the development
      of transgenic technology, which has opened up opportunities for studying events
      that occur after stage 40. In this chapter, I will give a brief descriptive
      background of some of the different types of regeneration studied in Xenopus, and
      provide protocols and morphological scoring information with the aim of
      facilitating progress in understanding regeneration in this model system.
      Additionally, some particularly elegant recent examples are used to highlight the
      advantages of Xenopus as a model for regeneration and the future opportunities
      that this offers.

PMID- 22956109
TI  - On-line resources for Xenopus.
AB  - Since the advent of computational methods in biology, the quantity of biological
      data has grown exponentially. These data support genomic, genetic, developmental,
      and other forms of biological experimentation. The number of on-line resources
      has kept pace with the growth in data. Xenopus has perhaps lagged some of the
      other model organisms in developing resources, but is now quickly catching up.
      There are now a number of well-established and developing resources for Xenopus.
      This chapter looks beyond the widely known public databases, Genbank and the EBI,
      and describes how the researcher can use a number of central sites such as
      Xenbase, UniProtKB, and major genome browsers to navigate to a variety of
      different resources.

PMID- 22956110
TI  - The effect of oxidative stress upon the intestinal uptake of folic acid: in vitro
      studies with Caco-2 cells.
AB  - Folic acid (FA) is a vitamin essential for normal cellular functions, growth, and
      development. Because humans cannot synthesize this micronutrient, it must be
      obtained from dietary sources through intestinal absorption. The intestinal tract
      is a major target for oxidative stress. Our aim was to investigate the effect of
      oxidative stress upon the uptake of FA by Caco-2 cells. Oxidative stress was
      induced by exposure of the cells to tert-butyl hydroperoxide (TBH) for 1 h. TBH
      (3,000 MUM) induced an increase in biomarkers of oxidative stress, while
      maintaining cell viability and proliferation. In relation to the apical uptake of
      (3)H-FA, TBH (3,000 MUM) reduced the cellular accumulation of (3)H-FA (10 nM),
      although the characteristics (kinetics, pH dependence, and inhibitory profile) of
      (3)H-FA uptake were not changed. This effect was associated with a decrease in
      the mRNA steady-state levels of proton-coupled folate transporter and folate
      receptor alpha and of the efflux transporter multidrug resistance protein 2.
      Moreover, TBH (3,000 MUM) did not affect the noncarrier-mediated apical uptake of
      (3)H-FA. Finally, the effect of TBH upon (3)H-FA apical uptake was not dependent
      on protein kinase A, protein kinase C, mitogen-activated protein kinases,
      phosphoinositide 3-kinase, nuclear factor kappa B, and protein tyrosine kinases,
      but was completely prevented by dietary polyphenols (resveratrol, quercetin, and
      EGCG). These results suggest that oxidative stress at the intestinal level may
      result in a reduction in the intestinal absorption of dietary FA and that
      polyphenolic dietary components may offer protection against oxidative stress
      induced inhibition of intestinal FA absorption.

PMID- 22956111
TI  - Toxicity of hydroquinone to different freshwater phototrophs is influenced by
      time of exposure and pH.
AB  - The interaction of natural organic matter with phytoplankton communities in
      freshwater ecosystems is an intensively studied subject matter. Previous studies
      showed that apparently plant-derived phenols were able to inhibit algal and
      cyanobacterial growth. Furthermore, it was also assumed that humic substances
      (HS), which comprise the major part of dissolved organic carbon in freshwater
      ecosystems, directly interact with freshwater phototrophs. For example, quinoid
      building blocks of HS were thought to be algicidal. To identify key environmental
      variable for the toxic action of potential quinone algicides, we tested the
      toxicity of hydroquinone (HQ) to different eukaryotic and prokaryotic freshwater
      phototrophs in terms of growth performance and investigated also the effect of HQ
      oxidation at different pH values on its algicidal potential. It was shown that
      cyanobacterial species were much more susceptible to hydroquinone than coccal
      green algal species were, with Microcystis aeruginosa being the most sensitive
      species by far. In addition, it was obvious that the aging of hydroquinone-stock
      solution at pH 11 led to polymerization and, by this process, to a total loss of
      toxicity; whereas the algicidal potential sustained if the polyphenol was kept at
      pH 7. Since most lakes with heavy blooms of phototrophs possess pH values clearly
      above 7.0, it is questionable, if polyphenols in general and quinones in
      particular are the effective chemicals and if litter and straw leachates are
      applied as means to combat algal and cyanobacterial blooms.

PMID- 22956112
TI  - Phytoremediation potential of Arabidopsis thaliana, expressing ectopically a
      vacuolar proton pump, for the industrial waste phosphogypsum.
AB  - Phosphogypsum (PG) is a by-product of the phosphorus-fertiliser industry and
      represents an environmental concern since it contains pollutants such as cadmium
      (Cd). We have recently shown that the overexpression of a proton pump gene
      (TaVP1) in transgenic tobacco (Nicotiana tabacum) led to an enhanced Cd tolerance
      and accumulation. The aim of this study was to evaluate the potential of
      transgenic Arabidopsis thaliana plants harbouring the TaVP1 gene to
      phytoremediate phosphogypsum. A pot experiment was carried out under greenhouse
      conditions. Transgenic A. thaliana plants harbouring the TaVP1 gene were grown on
      various substrates containing phosphogypsum (0, 25, 50 and 100 %) for 40 days. At
      the end of the growth period, we examined the growth (germination, root length,
      fresh weight) and physiological parameters (chlorophyll and protein contents,
      catalase activity and proteolysis) as well as the cadmium, Mg, Ca, and P contents
      of the A. thaliana plants. In order to evaluate Cd tolerance of the A. thaliana
      lines harbouring the TaVP1 gene, an in vitro experiment was also carried out. One
      week-old seedlings were transferred to Murashige and Skoog agar plates containing
      various concentrations of cadmium; the germination, total leaf area and root
      length were determined. The growth and physiological parameters of all A.
      thaliana plants were significantly altered by PG. The germination capacity, root
      growth and biomass production of wild-type (WT) plants were more severely
      inhibited by PG compared with the TaVP1 transgenic A. thaliana lines. In
      addition, TaVP1 transgenic A. thaliana plants maintained a higher antioxidant
      capacity than the WT. Interestingly, elemental analysis of leaf material derived
      from plants grown on PG revealed that the transgenic A. thaliana line accumulated
      up to ten times more Cd than WT. Despite its higher Cd content, the transgenic A.
      thaliana line performed better than the WT counterpart. In vitro evaluation of Cd
      tolerance showed that TaVP1 transgenic A. thaliana lines were more Cd-tolerant
      than the WT plants. These results suggested that ectopic expression of a vacuolar
      proton pump in A. thaliana plants can lead to various biotechnological
      applications including the phytoremediation of industrial wastes.

PMID- 22956113
TI  - Insecticide substitutes for DDT to control mosquitoes may be causes of several
      diseases.
AB  - Malaria continues to be a public health problem in Bangladesh, despite efforts in
      the 1960s to eradicate the vectors through the use of DDT. At one point,
      eradication of malaria was acclaimed but later on it reappeared. The use of DDT
      is no more legally allowed in Bangladesh, which has been officially replaced by a
      number organophosphates and/or synthetic pyrethroids and their combinations in
      addition to the integrated vector management (IVM) package. IVM being a community
      approach is still to go a long way to be mass popular. Adulticides, larvicides,
      residual sprays, mosquito coil, insecticide-impregnated curtain, aerosol, etc.
      still serve as the major weapons of mosquito control. Thus, mosquito control
      still mostly depends on chemical insecticides. Although the use of DDT is banned
      in Bangladesh, there are reports on its illegal use in different forms. Moreover,
      there is tons of leftover DDT in Bangladesh, which is likely to cause several
      diseases. As per one report, about 500 MTs of DDT stockpiles are lying in the
      Medical Sub-Depots at Chittagong for over a period of 26 years. DDT is a
      persistent organic pollutant pesticide, which can cause diseases like cancer,
      endocrine disorder, disruption of immune system, embryonic abnormality,
      reproductive disorder, etc. Other chemical insecticides, which are replacing DDT,
      are also not free of hazardous impacts. IVM thus appears to be a wise approach
      requiring concerted efforts for the management of mosquito to control malaria.
      Such an IVM comprises use of Bacillus thuringiensis Berliner var. israelensis,
      methoprene, biocontrol agents, cleaning of breeding sites, pyrethroid-impregnated
      curtain, etc. Therefore, a wise effort should be adopted to completely stop the
      use of DDT, eliminate its stockpiles wherever they are in Bangladesh and to
      popularise the IVM, not the chemicals-based alternatives throughout the country.

PMID- 22956114
TI  - Comparative study of biochemical and immunological biomarkers in three marine
      bivalves exposed at a polluted site.
AB  - A battery of biochemical and immunological biomarkers used for pollution
      assessment were measured for first time in the clams Venus verrucosa and Callista
      chione and were compared with those of the mussel Mytilus galloprovincialis, a
      well-established indicator organism utilized in numerous environmental monitoring
      programs. Clams and mussel were transplanted at a polluted and a reference site
      or maintained at the laboratory. Among biochemical biomarkers,
      acetylcholinesterase did not differ at the polluted site in all species, but
      there was a significant difference between the mussel and the clams, glutathione
      S-transferase showed a clear inhibition at the polluted site in all species and a
      significant difference between the two clams was also indicated, while catalase
      activities were increased only in V. verrucosa at the polluted site and not in
      mussel or the other clam. Immunological biomarkers responses were also pronounced
      at the polluted site. Lysozyme activity was species-dependent whereas respiratory
      burst activity measured as luminol-dependent chemiluminescence (CL) was site and
      stimulus dependent, and it was evident in M. galloprovincialis and V. verrucosa
      and not in C. chione. Further investigation focused on biochemical and
      immunological biomarkers related with the oxidative mechanisms in clams will
      strengthen and expand their use as bioindicators for pollution assessment.

PMID- 22956115
TI  - Neurotoxicological evaluation of microcystin-LR exposure at environmental
      relevant concentrations on nematode Caenorhabditis elegans.
AB  - Previous studies have not examined the adverse effects of microcystin-LR (MC-LR)
      at environmental relevant concentrations on the development and functions of
      nervous system. The neurotoxic effects of MC-LR exposure on neurotransmitter
      systems were investigated in Caenorhabditis elegans. After exposing L1 larvae to
      0.1, 1, 10, and 100 MUg l(-1) of MC-LR for 8 and 24 h, the adverse effects on
      GABAergic, cholinergic, serotonergic, dopaminergic, and glutamatergic neurons
      were examined. The expression levels of genes required for development and
      functions of GABAergic neurons were further investigated. Body bend frequency and
      head thrash frequency decreased significantly after MC-LR exposure for 8 h at
      concentrations more than 1 MUg l(-1) and after MC-LR exposure for 24 h at
      concentrations more than 0.1 MUg l(-1). Loss of GABAergic neurons increased
      significantly in a dose-dependent manner after MC-LR exposure at concentrations
      more than 0.1 MUg l(-1). In contrast, no obvious neuronal losses or morphologic
      changes were observed in cholinergic, serotonergic, dopaminergic, and
      glutamatergic neurons in MC-LR-exposed nematodes. Quantitative real-time PCR
      assay further showed that expression levels of unc-30, unc-46, unc-47, and exp-1
      genes required for development and function of GABAergic neurons decreased
      significantly in nematodes exposed to MC-LR at concentrations more than 0.1 or 1
      MUg l(-1). MC-LR at environmental relevant concentrations caused neurobehavioral
      defects, which may be largely due to the neuronal loss and the alterations of
      expression level of genes required for GABAergic neurotransmitter system in C.
      elegans.

PMID- 22956116
TI  - Fracture behavior of human molars.
AB  - Despite the durability of human teeth, which are able to withstand repeated
      loading while maintaining form and function, they are still susceptible to
      fracture. We focus here on longitudinal fracture in molar teeth-channel-like
      cracks that run along the enamel sidewall of the tooth between the gum line
      (cemento-enamel junction-CEJ) and the occlusal surface. Such fractures can often
      be painful and necessitate costly restorative work. The following study describes
      fracture experiments made on molar teeth of humans in which the molars are placed
      under axial compressive load using a hard indenting plate in order to induce
      longitudinal cracks in the enamel. Observed damage modes include fractures
      originating in the occlusal region ('radial-median cracks') and fractures
      emanating from the margin of the enamel in the region of the CEJ ('margin
      cracks'), as well as 'spalling' of enamel (the linking of longitudinal cracks).
      The loading conditions that govern fracture behavior in enamel are reported and
      observations made of the evolution of fracture as the load is increased.
      Relatively low loads were required to induce observable crack initiation
      approximately 100 N for radial-median cracks and 200 N for margin cracks-both of
      which are less than the reported maximum biting force on a single molar tooth of
      several hundred Newtons. Unstable crack growth was observed to take place soon
      after and occurred at loads lower than those calculated by the current fracture
      models. Multiple cracks were observed on a single cusp, their interactions
      influencing crack growth behavior. The majority of the teeth tested in this study
      were noted to exhibit margin cracks prior to compression testing, which were
      apparently formed during the functional lifetime of the tooth. Such teeth were
      still able to withstand additional loading prior to catastrophic fracture,
      highlighting the remarkable damage containment capabilities of the natural tooth
      structure.

PMID- 22956117
TI  - Emergency neurological life support: spinal cord compression (SCC).
AB  - Acute spinal cord compression (SCC) is the most serious of the diseases of the
      cord and should be accorded special attention in neurocritical care. Patients
      with SCC have a combination of motor and sensory dysfunction that has a
      distribution referable to one, or a few contiguous, spinal levels. Bowel and
      bladder dysfunction and neck or back pain are usually part of the clinical
      presentation but are not uniformly present. Because interventions are time
      sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol.

PMID- 22956118
TI  - Emergency neurological life support: status epilepticus.
AB  - Patients with prolonged or rapidly recurring convulsions lasting more than 5 min
      are in status epilepticus (SE) and require immediate resuscitation. Although
      there are relatively few randomized clinical trials, available evidence and
      experience suggest that early and aggressive treatment of SE improves patient
      outcomes, for which reason it was chosen as an Emergency Neurologic Life Support
      protocol. The current approach to the emergency treatment of SE emphasizes rapid
      initiation of adequate doses of first line therapy, as well as accelerated second
      line anticonvulsant drugs and induced coma when these fail, coupled with
      admission to a unit capable of neurologic critical care and
      electroencephalography monitoring. This protocol not only will focus on the
      initial treatment of SE but also review subsequent steps in the protocol once the
      patient is hospitalized.

PMID- 22956119
TI  - Prevalence of urinary tract infection and risk factors among Saudi patients with
      diabetes.
AB  - PURPOSE: The aim of this study is to assess the prevalence of urinary tract
      infection (UTI) and its risk factors among Saudi diabetics. METHOD: A total of
      1,000 diabetic patients were included. Patients were interviewed and examined at
      each visit every 6 months. RESULTS: The prevalence of UTI was 25.3 % in total
      diabetic population and 7.2 and 41.1 % in males and females, respectively.
      Females have highest risk of UTI (RR = 6.102; CI = 4.343-8.573; P < 0.001). Age,
      duration of diabetes and HbA1c did not influence the incidence of UTI, while BMI
      above 30 kg/m(2) increased the risk (RR = 1.722; CI = 1.532-1.935; P < 0.001).
      The incidence of UTI in both type 1 and 2 diabetics was similar (23.7 and 25.6
      %). There was no significant risk in patients aged above 60 years (RR = 1.054; CI
      = 0.841-1.321; P = 0.651). The risk factors found to be associated with UTI were
      hypertension (RR = 1.202; CI = 1.061-1.361; P = 0.006), insulin therapy (RR =
      1.411; CI = 1.262-1.578; P < 0.001) and nephropathy (microalbuminuria) (RR =
      1.417; CI = 1.036-1.939; P = 0.031). CONCLUSION: The present study has shown that
      prevalence of UTI is more in diabetic females and diabetics with BMI above 30
      kg/m(2). The other risk factors associated with UTI in general diabetic
      population were found to be microalbuminuria, hypertension and insulin therapy.

PMID- 22956120
TI  - Decreased activity of folate transporters in lipid rafts resulted in reduced
      hepatic folate uptake in chronic alcoholism in rats.
AB  - Folic acid is an essential nutrient that is required for one-carbon biosynthetic
      processes and for methylation of biomolecules. Deficiency of this micronutrient
      leads to disturbances in normal physiology of cell. Chronic alcoholism is well
      known to be associated with folate deficiency, which is due in part to folate
      malabsorption. The present study deals with the regulatory mechanisms of folate
      uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body
      weight/day ethanol (20 % solution) orally for 3 months, and the molecular
      mechanisms of folate uptake were studied in liver. The characterization of the
      folate transport system in liver basolateral membrane (BLM) suggested it to be a
      carrier mediated and acidic pH dependent, with the major involvement of proton
      coupled folate transporter and folate binding protein in the uptake. The folate
      transporters were found to be associated with lipid raft microdomain of liver
      BLM. Moreover, ethanol ingestion decreased the folate transport by altering the
      Vmax of folate transport process and downregulated the expression of folate
      transporters in lipid rafts. The decreased transporter levels were associated
      with reduced protein and mRNA levels of these transporters in liver. The deranged
      folate uptake together with reduced folate transporter levels in lipid rafts
      resulted in reduced folate levels in liver and thereby to its reduced levels in
      serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate
      uptake in liver, which was associated with the decreased number of transporter
      molecules in the lipid rafts that can be ascribed to the reduced synthesis of
      these transporters.

PMID- 22956121
TI  - Orthopaedic management in the polytrauma patient.
AB  - The past century has seen many changes in the management of the polytraumatized
      orthopaedic patient. Early recommendations for non-operative treatment have
      evolved into early total care (ETC) and damage control orthopaedic (DCO)
      treatment principles. These principles force the treating orthopaedist to take
      into account multiple patient parameters including hypothermia, coagulopathy and
      volume status before deciding upon the operative plan. This requires a
      multidisciplinary approach involving critical care physicians, anesthesiologists
      and others.

PMID- 22956122
TI  - Polydatin, a natural precursor of resveratrol, induces beta-defensin production
      and reduces inflammatory response.
AB  - It is well known that human keratinocytes produce the anti-microbial peptide beta
      defensin 2. Its production is enhanced by pathogenic microorganisms or other
      environmental stressors. In this study, we evaluated the effect of resveratrol, a
      polyphenol found in several dietary source as grape seed, and its natural
      precursor, polydatin on heat-stressed human keratinocytes. By reverse
      transcription-polymerase chain reaction and enzyme-linked immunoadsorbent assay,
      we demonstrated that resveratrol used in combination with polydatin was able to
      modulate interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha gene
      expression. In addition, our data show that resveratrol and polydatin increased
      the heat shock protein (Hsp)70B' gene expression, a Hsp that plays an important
      role in the cytoprotection and repair of cells and tissues. Worthy of note,
      polydatin used alone or in combination with resveratrol, increased the release of
      human beta-defensin 2. These results highlighted the ability of polydatin and
      resveratrol to reinforce cytoprotective response in stress conditions and suggest
      their use in cosmetic or pharmaceutical preparations.

PMID- 22956123
TI  - Association of toll-like receptor 4 polymorphisms with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade
      inflammatory state. Toll-like receptor 4 (TLR4) is a critical mediator of innate
      immunity. Polymorphisms in TLR4 gene have been shown to be associated with
      impaired inflammatory response. Here, we investigated the association of TLR4
      polymorphisms with T2DM. Four TLR4 polymorphisms (+986A/G, +1196C/T, +3725G/C,
      and +11367G/C) were genotyped in a total number of 822 T2DM patients and 835
      healthy controls. Results showed that the +986A/G and +1196C/T polymorphisms did
      not exist in the Han Chinese population. The prevalence of TLR4 +3725GC and CC
      genotypes were significantly decreased in T2DM cases than in controls (odds ratio
      (OR) = 0.62, 95 % confidence interval (CI) = 0.50-0.78, p = 3.48 * 10(-5), and OR
      = 0.36, 95 % CI = 0.22-0.59, p = 1.55 * 10(-5), respectively). Also, the
      frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p =
      2.46 * 10(-9)). When analyzing the TLR4 +11367G/C polymorphism, the +11367CC
      genotype revealed lower numbers in patients compared to healthy controls (OR =
      0.46, 95 % CI = 0.27-0.78, p = 0.0032). Analysis of the clinical features on the
      control subjects demonstrated no correlations between these TLR4 polymorphisms
      and sex, age, body mass index, etc. (p > 0.05). In conclusion, these data
      indicate that TLR4 +3725G/C and +11367G/C polymorphisms may be novel protective
      factors against T2DM in the Chinese population.

PMID- 22956124
TI  - Safety advantage of modified minimally invasive cardiac surgery for pediatric
      patients.
AB  - Minimally invasive cardiac surgery (MICS) using a small surgical incision in
      children provides less physical stress. However, concern about safety due to the
      small surgical field has been noted. Recently, the authors developed a modified
      MICS procedure to extend the surgical field. This report assesses the safety and
      benefit of this modified procedure by comparing three procedures: the modified
      MICS (group A), conventional MICS (group B), and traditional open heart surgery
      (group C). A retrospective analysis was performed with 111 pediatric patients
      (age, 0-9 years; weight, 5-30 kg) who underwent cardiac surgery for simple
      cardiac anomaly during the period 1996-2010 at Juntendo University Hospital. The
      modified MICS method to extend the surgical view has been performed since 2004. A
      skin incision within 5 cm was made below the nipple line, and the surgical field
      was easily moved by pulling up or down using a suture or a hemostat. The results
      showed no differences in terms of gender, age, weight, or aortic cross-clamp time
      among the groups. Analysis of variance (ANOVA) indicated significant differences
      in mean time before cardiopulmonary bypass (CPB), CPB time, operation time, and
      bleeding. According to the indices, modified MICS was similar to traditional open
      surgery and shorter time or lower bleeding volume than conventional MICS. No
      major mortality or morbidity occurred. In conclusion, the modified MICS
      procedure, which requires no special techniques, was as safe as conventional open
      heart surgery and even reduced perioperative morbidity.

PMID- 22956126
TI  - Design and analytical issues: a response to "long-term effects of tongue piercing
      -a case control study".

PMID- 22956125
TI  - SUI-family genes encode phosphatidylserine synthases and regulate stem
      development in rice.
AB  - In vascular plants, the regulation of stem cell niche determines development of
      aerial shoot which consists of stems and lateral organs. Intercalary meristem
      (IM) controls internode elongation in rice and other grasses, however little
      attention has been paid to the underlying mechanism of stem cell maintenance.
      Here, we investigated the stem development in rice and showed that the Shortened
      Uppermost Internode 1 (SUI1) family of genes are pivotal for development of rice
      stems. We demonstrated that SUI-family genes regulate the development of IM for
      internode elongation and also the cell expansion of the panicle stem rachis in
      rice. The SUI-family genes encoded base-exchange types of phosphatidylserine
      synthases (PSSs), which possessed enzymatic activity in a yeast complementary
      assay. Overexpression of SUI1 and SUI2 caused outgrowths of internodes during
      vegetative development, and we showed that expression patterns of Oryza Sativa
      Homeobox 15 (OSH15) and Histone4 were impaired. Furthermore, genome-wide gene
      expression analysis revealed that overexpression and RNA knockdown of SUI-family
      genes affected downstream gene expression related to phospholipid metabolic
      pathways. Moreover, using Ultra-performance liquid chromatography-quadrupole time
      of flight-mass spectrometry, we analyzed PS contents in different genetic
      backgrounds of rice and showed that the quantity of very long chain fatty acids
      PS is affected by transgene of SUI-family genes. Our study reveals a new
      mechanism conveyed by the SUI1 pathway and provides evidence to link lipid
      metabolism with plant stem cell maintenance.

PMID- 22956127
TI  - Effect of polymerisation and ageing on the incremental bond strength of ormocer
      based dental materials.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of polymerisation
      and ageing on the incremental bond strength (IBS) and fracture mechanics of
      experimental and commercial, well established ormocer-based materials. METHODS:
      An experimental dimethacrylate-diluent-free ormocer was compared with two
      commercial products (Admira (VOCO); Ceram X Duo (Dentsply)). For Ceram X Duo, the
      strength between dentin shades (DD) and between dentin and enamel shades (DE) was
      measured. In order to simulate clinical conditions, when a direct access to the
      composite surface is impeded, the curing unit was applied at different distances
      (1, 3 or 6 mm) from the sample's surface. IBS was measured after the samples were
      stored in distilled water (24 h/37  degrees C) and after ageing (5,000 cycles
      between 5 and 55  degrees C followed by storage (28 days/37  degrees C) in
      distilled water). Additionally, the degree of cure (DC) was measured in a thin
      film (~50 MUm). A multivariate analysis, an additional one-way ANOVA with Tukey
      HSD post hoc test (alpha = 0.05), an independent t test (alpha = 0.05), and
      Weibull statistics were used to assess the results. RESULTS: After 24 h, the
      values for IBS were statistically the same. Differences revealed after ageing,
      whereby the experimental material achieved the significant highest and Admira the
      lowest results. By evaluating after 24 h and after ageing, the experimental
      material obtained the smallest Weibull modulus "m". The predominant breaking
      mechanism is cohesive, even though the number decreases in favour for the mixture
      and adhesive fractures after ageing. Clear differences arose with regard to DC.
      The experimental material reached considerably lower values (31.9-33.2 %) unlike
      Ceram X Duo (45.6-48.3 %) and Admira (52.9-58.8 %). CONCLUSIONS: The IBS and the
      DC are far more dependent on the parameter filler volume percent and material
      than on the polymerisation distance. CLINICAL SIGNIFICANCE: A dimethacrylate
      diluent-free ormocer matrix offers a better stability opposite ageing but
      achieves a lower DC and reliability.

PMID- 22956129
TI  - On setting up and assessing docking simulations for virtual screening.
AB  - Small molecule docking and virtual screening of candidate compounds have become
      an integral part of drug discovery pipelines, complementing and streamlining
      experimental efforts in that regard. In this chapter, we describe specific
      software packages and protocols that can be used to efficiently set up a
      computational screening using a library of compounds and a docking program. We
      also discuss consensus- and clustering-based approaches that can be used to
      assess the results, and potentially re-rank the hits. While docking programs
      share many common features, they may require tailored implementation of virtual
      screening pipelines for specific computing platforms. Here, we primarily focus on
      solutions for several public domain packages that are widely used in the context
      of drug development.

PMID- 22956128
TI  - Fermentation of sugars and sugar alcohols by plaque Lactobacillus strains.
AB  - OBJECTIVE: The objective was to analyse the ability of Lactobacillus strains
      isolated from supragingival plaque of subjects with hyposalivation and from
      healthy controls to ferment sugars and sugar alcohols. MATERIAL AND METHODS:
      Fifty strains isolated from interproximal plaque from subjects with radiation
      induced hyposalivation (25 strains), subjects with primary Sjogren's syndrome (16
      strains) and from subjects with normal salivary secretion rate (9 strains) were
      tested. Growth and pH were determined after 24 and 48 h of anaerobic incubation
      in vials containing basal media with 1 % of glucose, fructose, sucrose, mannitol,
      sorbitol or xylitol. RESULTS: No differences between strains isolated from
      hyposalivated subjects and controls were detected. All strains lowered the pH to
      <5.0 from fructose and the majority of the strains from glucose and sucrose. A pH
      of <5.5 was seen for 52 % of the strains using mannitol, 50 % using sorbitol and
      36 % using xylitol. The ability to produce acids from sugars and sugar alcohols
      was highest among strains of Lactobacillus rhamnosus, Lactobacillus casei and
      Lactobacillus paracasei and lowest among Lactobacillus fermentum strains.
      CONCLUSION: A large number of Lactobacillus strains are able to ferment not only
      sugars but also the sugar substitutes mannitol, sorbitol and xylitol to pH levels
      critical for enamel demineralisation. CLINICAL RELEVANCE: Our findings suggest
      that products containing mannitol, sorbitol and/or xylitol may contribute to the
      acidogenic potential of the dental plaque and especially in hyposalivated
      subjects with high numbers of lactobacilli.

PMID- 22956130
TI  - Virtual ligand screening combined with NMR to identify Dvl PDZ domain inhibitors
      targeting the Wnt signaling.
AB  - Virtual ligand screening is a powerful technique to identify potential hits of
      targets and to increase hit rates. Here, we describe how we used this technique
      combined with NMR (15)N HSQC experiments to obtain small molecules that bind to
      the PDZ domain of Dvl targeting the Wnt signaling pathway.

PMID- 22956131
TI  - Rational design of Rho GTPase-targeting inhibitors.
AB  - Rho GTPases have been implicated in diverse cellular functions and are potential
      therapeutic targets in inflammation, cancer, and neurologic diseases. Virtual
      screening of compounds that fit into surface grooves of RhoA known to be critical
      for guanine nucleotide exchange factor (GEF) interaction produced chemical
      candidates with minimized docking energy. Subsequent screening for inhibitory
      activity of RhoA binding to the Rho-GEF, LARG, identified a Rho-specific
      inhibitor as a lead compound capable of blocking RhoA-LARG interaction and RhoA
      activation by LARG specifically and dose dependently. A microscale thermophoresis
      analysis was applied to directly quantify the binding interaction of the lead
      inhibitor with RhoA target. The lead inhibitor highlights the principle that
      rational targeting of subfamily members of Rho GTPases is feasible and
      potentially useful in future drug design effort.

PMID- 22956132
TI  - Rational design of peptide ligands against a glycolipid by NMR studies.
AB  - Ganglioside GD2 is a cell surface glycosphingolipid that is targeted clinically
      for cancer diagnosis, prognosis, and therapy. The conformations of free GD2 and
      of GD2 bound to anti-GD2 mAb 3F8 were resolved by saturation transfer difference
      nuclear magnetic resonance and molecular modeling. Then small molecule cyclic
      peptide ligands that bind to GD2 selectively were designed, and shown to affect
      GD2-mediated signal transduction. The solution structure of the GD2-bound
      conformation of the peptide ligands showed an induced-fit binding mechanism. This
      work furthers the concept of rationally designing ligands for carbohydrate
      targets; and may be expanded to other clinically relevant gangliosides.

PMID- 22956133
TI  - A combinatorial strategy for the acquisition of potent and specific protein
      tyrosine phosphatase inhibitors.
AB  - Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes,
      regulate many cellular processes, such as proliferation, differentiation,
      migration, apoptosis, and immune responses. Small molecule inhibitors against
      PTPs are valuable both as powerful tools to study the functions of target PTPs
      and as lead compounds for pharmacological development. Here, we describe a novel
      combinatorial library approach to target simultaneously both the active site
      pocket and a peripheral secondary binding site for the acquisition of potent and
      specific PTP inhibitors. Fluorescence tagging during combinatorial library
      synthesis enables fluorescence polarization-based high-throughput screening of
      the resulting library, leading to identification of a TC-PTP inhibitor.

PMID- 22956134
TI  - Identification of allosteric inhibitors of p21-activated kinase.
AB  - Protein kinases are among the most important drug targets; however the structural
      conservation of the ATP-binding pocket of kinases can lead to promiscuous
      inhibition of additional unintended kinase targets. Allosteric inhibitors that
      target less conserved regions of protein kinases represent an alternative
      approach that may provide more selective kinase inhibition. In this report,
      protocols are provided for the screening and identification of Pak1 inhibitors
      acting via an allosteric mechanism.

PMID- 22956135
TI  - Using a modified yeast two-hybrid system to screen for chemical GEF inhibitors.
AB  - GTPases of the Ras superfamily act as signaling switches, active when bound to
      GTP and inactive when bound to GDP. There is now considerable evidence that over
      activation of Ras-like pathways participates in the development of many cancer
      types. In particular, GTPases of the Rho family control cell adhesion, survival,
      motility, and invasion, cell properties dysregulated in most cancer types. Rho
      activation is triggered by RhoGEFs, most of which form complexes with growth
      factor receptors and initiate downstream Rho signaling pathways in response to
      extracellular clues. As such, RhoGEFs represent attractive targets to inhibit Rho
      pathways and may have interesting druggability for cancer therapeutics. Here we
      describe a procedure derived from the yeast two-hybrid system, in which
      activation of a mammalian Rho GTPase by its cognate RhoGEF is converted into
      variation in the yeast growth. The experimental design is thus suitable for
      identiying RhoGEF inhibitors and has been optimized for medium-throughput
      screening. The major advantages of this method lie in the direct monitoring of
      GEF activity in a living organism and the rapid detection of false positive hits.

PMID- 22956136
TI  - Random mutagenesis of peptide aptamers as an optimization strategy for inhibitor
      screening.
AB  - Accumulating work over the past decade has shown that peptide aptamer screening
      represents a valid strategy for inhibitor identification that can be applied to a
      variety of different targets. Because of the screening method in cells and the
      highly combinatorial libraries available, this approach yields rapidly highly
      specific candidate inhibitors. Once a hit peptide has been identified, its
      interaction strength and affinity towards its target protein can be optimized
      even more, in order to increase its inhibition efficiency when subsequently
      applied in vivo. A condition to a successful optimization is that gain of
      inhibition strength should not result in loss of specificity. Here we present a
      simple method for peptide aptamer optimization, which can be achieved by PCR
      based random mutagenesis combined with a selection screen in yeast using a strong
      selective drug. The rationale of this approach, which has proven valid and
      efficient, is that stronger interaction in yeast will also lead to stronger
      inhibition. Our optimization method is effective, without loss of specificity,
      which is of a great importance for the discovery of inhibitors that target
      specific protein-protein interactions.

PMID- 22956137
TI  - A screening strategy for trapping the inactive conformer of a dimeric enzyme with
      a small molecule inhibitor.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of
      Kaposi's sarcoma (KS), the most common cancer in AIDS patients. All herpesviruses
      express a conserved dimeric serine protease that is required for generating
      infectious virions and is therefore of pharmaceutical interest. Given the past
      challenges of developing drug-like active-site inhibitors to this class of
      proteases, small-molecules targeting allosteric sites are of great value. In
      light of evidence supporting a strong structural linkage between the dimer
      interface and the protease active site, we have focused our efforts on the dimer
      interface for identifying dimer disrupting inhibitors. Here, we describe a high
      throughput screening approach for identifying small molecule dimerization
      inhibitors of KSHV protease. The helical mimetic, small molecule library used, as
      well as general strategies for selecting compound libraries for this application
      will also be discussed. This methodology can be applicable to other systems where
      an alpha helical moiety plays a dominant role at the interaction site of
      interest, and in vitro assays to monitor function are in place.

PMID- 22956138
TI  - Use of a fluorescent ATP analog to probe the allosteric conformational change in
      the active site of the protein kinase PDK1.
AB  - There is growing interest in exploring allosteric sites on proteins for drug
      discovery. At the center of the regulation of many protein kinases from the AGC
      family there is an allosteric site termed "PIF-pocket." The regulated binding of
      a C-terminal region of the kinase to the PIF-pocket, within the small lobe of the
      catalytic core, modulates the activity of AGC kinases. Small compounds that bind
      to the PIF-pocket can mimic its physiological mechanism of regulation and
      modulate the kinase activity in vitro, e.g., small compounds can activate the
      phosphoinositide-dependent protein kinase 1 (PDK1). Compounds binding to an
      allosteric site on a protein kinase may produce conformational changes at the ATP
      binding site within the active site of the kinase domain. We here describe a
      fluorescent method using the ATP analog TNP-ATP that allows evaluating the
      allosteric conformational changes at the ATP-binding site of PDK1 triggered by
      small compounds binding to the PIF-pocket.

PMID- 22956139
TI  - Affinity purification of protein kinases that adopt a specific inactive
      conformation.
AB  - Several protein kinases have been characterized in a specific inactive form
      called the DFG-out conformation. Unlike the active conformation which is
      conserved in all kinases, the inactive DFG-out conformation appears to be
      accessible to only certain kinases. This inactive conformation has been
      successfully targeted with highly selective kinase inhibitors, including the
      cancer drugs imatinib and sorafenib. However, the structural and sequence
      requirements for adopting this conformation are still poorly understood. Here, we
      describe a general method for enriching DFG-out adopting kinases from cell
      lysates with an affinity resin that contains a general ligand that specifically
      recognizes this inactive form.

PMID- 22956140
TI  - Determination of the kinetics and thermodynamics of ligand binding to a specific
      inactive conformation in protein kinases.
AB  - Recent interest in inactive kinase conformations has generated the need to
      develop new biochemical tools to study them. Here, we describe the use of a
      fluorescent probe that selectively and potently binds to a specific inactive
      conformation of protein kinases. This allows for the thermodynamics and kinetics
      of ligand binding to be determined.

PMID- 22956141
TI  - Purification and specific assays for measuring APE-1 endonuclease activity.
AB  - Human apurinic/apyrimidinic endonuclease-1 (APE-1) is essential for base excision
      repair and plays a major role in DNA repair and maintaining genomic stability.
      Cancer cells treated with conventional DNA-damaging agents develop resistance due
      in part to upregulation of enzymes involved in DNA repair. It is hypothesized
      that inhibiting DNA repair machinery should sensitize the cells to DNA-damaging
      agents. Previously, it has been shown that APE-1 is implicated in drug resistance
      and cancer progression. Therefore, APE-1 inhibitors are being sought after for
      their synergistic properties with various chemotherapeutics agents. Screening of
      several compound libraries and optimization of known inhibitors of APE-1
      endonuclease activity have been accelerated by the use of high-throughput
      screening. Nevertheless, potential inhibitors must be tested in other
      counterscreens to validate their selectivity for APE-1. Here, we describe in
      depth protocols for APE-1 purification and development of assays specific for APE
      1 endonuclease activity.

PMID- 22956142
TI  - An in vitro screening to identify drug-resistant mutations for target-directed
      chemotherapeutic agents.
AB  - The discovery of oncogenes and tumor suppressors as a driver of cancer
      development has triggered the development of target-specific small molecule
      anticancer compounds. As exemplified by Imatinib (Gleevec), a specific inhibitor
      of the Chronic Myeloid Leukemia-associated BCR/ABL kinase, these agents promise
      impressive activity in clinical trials, with low levels of clinical toxicity.
      However, such therapy is susceptible to the emergence of drug resistance mainly
      due to amino acid substitutions in the target protein. Defining the spectrum of
      such mutations is important for patient monitoring and the design of next
      generation inhibitors. Using Imatinib and BCR/ABL as a paradigm for a drug-target
      pair, we reported a retroviral vector-based screening strategy to identify the
      spectrum of resistance-conferring mutations, which has helped in designing the
      next-generation BCR/ABL inhibitors such as Nilotinib, Dasatinib, and Ponatinib.
      Here we provide a detailed methodology for the screen, which can be generally
      applied to any drug-target pair.

PMID- 22956143
TI  - Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone
      marrow cells.
AB  - MicroRNAs (miRNAs) are highly conserved small RNAs which regulate gene expression
      primarily through base pairing to the 3' untranslated region of target messenger
      RNA (mRNA), leading to mRNA degradation or translation inhibition depending on
      the complementarity between the miRNA and target mRNA. Single miRNA regulates
      multiple target mRNA. miRNAs have been shown to regulate gene expression in the
      hematopoietic stem cells, as well as at key decision points for various lineages.
      However, aberrant expression of miRNAs has been documented in cancer and disease
      models. Rigorous dissection of miRNA pathways and biology requires facile loss of
      function modeling. This chapter describes detailed protocol for knockdown miRNA
      21 which is involved in myelopoiesis using antagomiRs in primary murine bone
      marrow stem/progenitor cells.

PMID- 22956144
TI  - Synthesis, conjugation, and labeling of multifunctional pRNA nanoparticles for
      specific delivery of siRNA, drugs, and other therapeutics to target cells.
AB  - RNA is unique in nanoscale fabrication due to its amazing diversity of function
      and structure. RNA nanoparticles can be fabricated with a level of simplicity
      characteristic of DNA while possessing versatile tertiary structure and catalytic
      function similar to that of proteins. A large variety of single stranded loops
      are suitable for inter- and intramolecular interactions, serving as mounting
      dovetails in self-assembly without the need for external linking dowels. Novel
      properties of RNA nanoparticles have been explored for treatment and detection of
      diseases and various other realms. The higher thermodynamic stability, holding of
      noncanonical base pairing, stronger folding due to base stacking properties, and
      distinctive in vivo attributes make RNA unique in comparison to DNA. Indeed, the
      potential application of RNA nanotechnology in therapeutics is an exciting area
      of research. The use of RNAi in biomedical research has opened up new
      possibilities to silence or regulate the biological function of individual genes.
      Small interfering RNA (siRNA) has been extensively explored to genetically
      manipulate the expression in vitro and in vivo of particular genes identified to
      play a key role in cancerous or viral diseases. However, the efficient silencing
      of the desired gene depends upon efficient delivery of siRNA to targeted cells,
      as well as in vivo stability. In this chapter, we use the bacteriophage phi29
      motor pRNA-derived nanocarrier as a polyvalent targeted delivery system,
      introduce the potential of RNA-based therapeutics using nanobiotechnology or
      nanotechnology methods with the fabrication and modification of pRNA
      nanoparticles, and highlight its potential to become a valuable research tool and
      viable clinical approach for gene therapy.

PMID- 22956145
TI  - Mouse models for tumor metastasis.
AB  - Tumor metastasis is the main cause of death of cancer patients. Here we describe
      two mouse models for investigating tumor metastasis. In the first spontaneous
      metastasis mouse model, 4T1 mouse breast tumor cells are injected into the
      mammary gland of host mice and the metastasis of 4T1 tumor cells into the lung
      are examined with a colonogenic assay. In the second experimental metastasis
      mouse model, luciferase-labeled MDA-MB-231 human breast tumor cells are injected
      into the tail vein of NOD-SCID immunodeficient mice and the colonization of MDA
      MB-231 tumor cells in the lung are monitored using noninvasive bioluminescence
      imaging.

PMID- 22956146
TI  - Regulation of nicotinic acetylcholine receptor turnover by MuRF1 connects muscle
      activity to endo/lysosomal and atrophy pathways.
AB  - Muscle atrophy is a process of muscle wasting induced under a series of catabolic
      stress conditions, such as denervation, disuse, cancer cachexia, heart and renal
      failure, AIDS, and aging. Neuromuscular junctions (NMJs), the synapses between
      motor neurons and muscle fibers undergo major changes in atrophying muscles,
      ranging from mild morphological alterations to complete disintegration. In this
      study, we hypothesized that remodeling of NMJs and muscle atrophy could be linked
      together. To test this, we examined if a major atrophy-promoting E3 ubiquitin
      ligase, MuRF1, is involved in the maintenance of NMJs. Immunofluorescence
      revealed that MuRF1 is highly enriched close to the NMJ. Affinity precipitation
      and in vivo imaging showed that MuRF1 interacts in endocytic structures with
      both, acetylcholine receptor, the primary postsynaptic protein of the NMJ, as
      well as with Bif-1, an autophagy- and endocytosis-regulating factor. In vivo
      imaging, radio labeling, and weighing approaches demonstrated that metabolic
      destabilization of acetylcholine receptors and muscle atrophy induced by
      denervation were significantly rescued in MuRF1-KO animals. Notably, interaction
      with Bif-1, and the rescue of AChR lifetime and muscle atrophy were specific to
      MuRF1 but not MuRF2. Our data demonstrate an involvement of MuRF1 in membrane
      protein-turnover, including the degradation of AChRs at the NMJ under atrophying
      conditions where MuRF1 also interacts and associates with Bif-1. 

PMID- 22956147
TI  - Negative regulators of schwann cell differentiation-novel targets for peripheral
      nerve therapies?
AB  - As myelinating glial cells of the peripheral nervous system, Schwann cells wrap
      around axons and thereby provide insulation, acceleration of electric signal
      propagation, and axonal protection and maintenance. Schwann cells are main
      effectors for regeneration in a variety of peripheral neuropathic conditions,
      including inherited, inflammatory, toxic, and diabetic neuropathies, as well as
      traumatic injuries to peripheral nerve fibers. Due to their high differentiation
      plasticity, these cells can respond to injury and disease by myelin sheath
      degradation, dedifferentiation into an immature Schwann cell-like phenotype,
      proliferation, and remyelination of sprouting axons. In doing so, they can
      support and promote axonal regrowth and target tissue innervation. Developmental
      differentiation as well as regenerative de- and redifferentiation are tightly
      controlled by a balance of positive and negative regulators of Schwann cell
      maturation. Since misregulated expression of such negative regulators is
      potentially involved in inefficient or failed regeneration, we will provide an
      overview about recent work revealing the complex interactions between extrinsic
      and intrinsic signals in the inhibition of Schwann cell differentiation.

PMID- 22956148
TI  - Effect of di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate on in
      vitro developmental competence of bovine oocytes.
AB  - In the last decade, potential exposure of humans and animals to industrial
      chemicals and pesticides has been a growing concern. In the present study, di-(2
      ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) were used
      to model the effects of endocrine-disrupting compounds and their risk in relation
      to early embryonic losses. Exposure of cumulus oocyte complexes during maturation
      to 50 MUM MEHP reduced the proportion of oocytes that underwent nuclear
      maturation (p < 0.05) and increased the proportion of apoptotic oocytes (p <
      0.05). Furthermore, phthalates reduced cleavage rate in the MEHP-treated group (p
      < 0.05) and the proportion of embryos developing to the blastocyst stage in both
      DEHP- and MEHP-treated groups (p < 0.05). The total cell count for blastocysts
      developing from MEHP-treated oocytes was lower than in controls (p < 0.05).
      Exposure of oocytes to MEHP during maturation reduced (p < 0.05) the expression
      of ASAH1 (an anti-apoptotic factor), CCNA2 (involved in cell cycle control), and
      POU5F1 (responsible for pluripotency) in matured oocytes. Furthermore, the
      reduced mRNA expression of POU5F1 and ASAH1 lasted into two-cell stage embryos (p
      < 0.05). Phthalate-induced alterations in POU5F1, ASAH1, and CCNA2 expression
      might explain in part the reduced developmental competence of MEHP-treated
      oocytes.

PMID- 22956149
TI  - Placement of thoracolumbar pedicle screws using O-arm-based navigation: technical
      note on controlling the operational accuracy of the navigation system.
AB  - Suboptimal placements of pedicle screws may lead to neurological and vascular
      complications. Computer-assisted image guidance has been shown to improve
      accuracy in spinal instrumentation. Checking the accuracy of the navigation
      system during pedicle screw placement is fundamental. We describe a novel
      technique of using continuous accuracy check of the navigation system during O
      arm-based neuronavigation to instrument the thoracolumbar region. Forty thoracic
      and 42 lumbar screws were inserted in 12 patients. The Mirza evaluation system
      was used to evaluate the accuracy of the inserted screws. There was no
      neurological injury and no need to reposition any screw. The accuracy of the
      screws placement was excellent. Our technique of continuous at will operational
      accuracy check of the neuronavigation system is associated with extreme accuracy
      of screw placement, no need to bring a patient back to the operating room to
      reposition a pedicle screw, and with excellent outcome.

PMID- 22956150
TI  - Cholinergic precursors modulate the expression of heme oxigenase-1, p21 during
      astroglial cell proliferation and differentiation in culture.
AB  - Heme oxygenase-1 (HO-1) plays a crucial role in oxidative stress processes,
      apoptosis and cell differentiation. Further, some proteins related to cell cycle
      including cyclins and p21 are important markers of astrocyte cultures. Aim of
      investigation was to study the effects of cholinergic precursors (choline, CDP
      choline, Acetylcholine and alpha-Glyceril-Phosphorylcholine) on HO-1 and p21
      expression during astroglial cell proliferation and differentiation in primary
      cultures at 14 and 35 days in vitro (DIV) treated for 24 h with choline
      metabolites. Our results showed a slight reduction of HO-1 expression (data not
      statistical significant) in astroglial cell cultures treated with CDP-choline at
      14 DIV and 35 DIV. On the contrary, ACh and choline induced a significant
      increase of HO-1 expression in 14 DIV astrocyte cultures. Surprisingly, choline
      and ACh dramatically reduced HO-1 expression at 35 DIV. A slight decrease not
      statistical significant was detectable for alpha-GPC at 14 DIV and particularly
      significant at 35 DIV. Data concerning p21 expression, a well known protein
      inhibiting cell cycle, evidenced a significant increase at 14 and 35 DIV after
      alpha-GPC treatment. CDP-choline treatment caused a high increase of p21
      expression in 14 DIV astrocyte cultures, but no modification at 35 DIV. Instead,
      ACh treatment induced a marked increment of p21 expression at 35 DIV. Our data
      suggest that cholinergic precursors modulate HO-1 and p21 expression during
      astroglial cell proliferation and differentiation in culture and could be
      considered a tool to study the induced effects of ischemia and hypoxia diseases
      in some in vitro models to prevent and reduce its effects after treatment with
      cholinergic drugs.

PMID- 22956151
TI  - Immune thrombocytopenia in the elderly: clinical course in 525 patients from a
      single center in China.
AB  - Immune thrombocytopenia (ITP), often diagnosed in the elderly, is a hematologic
      disorder induced by autoimmune mechanism. In this retrospective study, we
      evaluated the clinical features, the risk of bleeding, and the response to
      treatment in 525 elderly ITP patients (age >=60 years) diagnosed at our center
      from 1980 to 2009. There were more females at 60-74 years of age (P = 0.044). The
      median duration of follow-up was 27 months (range 1-253 months). Ten patients
      developed thrombosis during treatment of ITP. At diagnosis, 461 patients (87.8 %)
      had signs of bleeding. The risk of severe bleeding was associated with both
      platelet count (P < 0.001; odds ratio (OR), 0.973) and age (P = 0.025; OR,
      1.039). The cutoff points in the platelet count at which bleeding and severe
      bleeding would begin to appear were 29.5 * 10(9) and 21.5 * 10(9)/L,
      respectively. Sixteen of 144 patients (11.1 %) who did not receive any treatment
      achieved remission spontaneously. The total response rate to treatment was 62.4 %
      (166/266). The median time to remission was 7 days, and combined use of
      intravenous immunoglobulin and steroids took effect faster than use of steroids
      alone (P = 0.001). Fifty-two patients (31.3 %) relapsed during follow-up. Of the
      27 patients who died during follow-up, seven deaths were directly attributed to
      ITP. In conclusion, the response rate has been improved since the last 10 years.
      ITP is also a self-limited disease to some extent in the elderly, but easy to
      relapse. This review represents the largest collection of elderly ITP patients in
      China in a single center.

PMID- 22956152
TI  - Monolingual coprolalia in bilingual patients with Tourette syndrome.

PMID- 22956153
TI  - Effect of diurnal temperature range on cardiovascular markers in the elderly in
      Seoul, Korea.
AB  - While diurnal temperature range (DTR) has been found to be a risk factor for
      mortality, evaluation of the underlying mechanisms involved in this association
      are lacking. To explain the association between DTR and health effects, we
      investigated how cardiovascular markers responded to DTR. Data was obtained from
      560 participants who regularly attended a community elderly welfare center
      located in Seoul, Korea. Data collection was conducted a total of five times over
      a 3-year period beginning in August, 2008. We examined systolic and diastolic
      blood pressure (BP), heart rate (HR), and heart rate variability (HRV). Mixed
      effects models and generalized additive mixed models were used to assess the
      relationship of DTR with BP, HR, and HRV. BP was not associated significantly
      with rapid temperature changes during the day. While HR was associated linearly
      with increments of DTR, the relationship between DTR and HRV showed nonlinear
      associations, or the presence of a cutoff around median DTR. At the cutoff level
      of DTR determined by an inflection point in the graph, standard deviation of
      normal-to-normal intervals (SDNN) and root mean square successive difference
      (RMSSD) were peaked, whereas the low frequency:high frequency (LF:HF) ratio was
      elevated with decreasing DTR below the cutoff level. The study demonstrated that
      HR increases with increasing temperature range during the day, and that HRV is
      reduced at small or large DTR, which suggests minimal cardiovascular stress
      around the median level of temperature range during the day.

PMID- 22956154
TI  - Obstructive jaundice as recurrence of lung adenocarcinoma.

PMID- 22956155
TI  - Next generation diagnostics in inherited arrhythmia syndromes : a comparison of
      two approaches.
AB  - Next-generation sequencing (NGS) provides an unprecedented opportunity to assess
      genetic variation underlying human disease. Here, we compared two NGS approaches
      for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR
      based target enrichment and long-read sequencing (PCR-LR) with in-solution
      hybridization-based enrichment and short-read sequencing (Hyb-SR). The PCR-LR
      assay comprehensively assessed five long-QT genes routinely sequenced in
      diagnostic laboratories and "hot spots" in RYR2. The Hyb-SR assay targeted 49
      genes, including those in the PCR-LR assay. The sensitivity for detection of
      control variants did not differ between approaches. In both assays, the major
      limitation was upstream target capture, particular in regions of extreme GC
      content. These initial experiences with NGS cardiovascular diagnostics achieved
      up to 89 % sensitivity at a fraction of current costs. In the next iteration of
      these assays we anticipate sensitivity above 97 % for all LQT genes. NGS assays
      will soon replace conventional sequencing for LQT diagnostics and molecular
      pathology.

PMID- 22956159
TI  - Detection and boundary identification of phonocardiogram sounds using an expert
      frequency-energy based metric.
AB  - This paper presents a new method to detect and to delineate phonocardiogram (PCG)
      sounds. Toward this objective, after preprocessing the PCG signal, two windows
      were moved on the preprocessed signal, and in each analysis window, two frequency
      and amplitude-based features were calculated from the excerpted segment. Then, a
      synthetic decision making basis was devised by combining these two features for
      being used as an efficient detection-delineation decision statistic, (DS). Next,
      local extremums and locations of minimum slopes of the DS were determined by
      conducting forward-backward local investigations with the purpose of detecting
      sound incidences and their boundaries. In order to recognize the delineated PCG
      sounds, first, S1 and S2 were detected. Then, a new DS was regenerated from the
      signal whose S1 and S2 were eliminated to detect occasional S3 and S4 sounds.
      Finally, probable murmurs and souffles were spotted. The proposed algorithm was
      applied to 52 min PCG signals gathered from patients with different valve
      diseases. The provided database was annotated by some cardiology experts equipped
      by echocardiography and appropriate computer interfaces. The acquisition
      landmarks were in 2R (aortic), 2L (pulmonic), 4R (apex) and 4L (tricuspid)
      positions. The acquisition sensor was an electronic stethoscope (3 M Littmann(r)
      3200, 4 kHz sampling frequency). The operating characteristics of the proposed
      method have an average sensitivity Se = 99.00% and positive predictive value PPV
      = 98.60% for sound type recognition (i.e., S1, S2, S3 or S4).

PMID- 22956158
TI  - Hemodynamic response to repeated noxious cold pressor tests measured by
      functional near infrared spectroscopy on forehead.
AB  - The objective of this research was to assess the utility of a simple near
      infrared spectroscopy (NIRS) technology for objective assessment of the
      hemodynamic response to acute pain. For this exploration, we used functional near
      infrared spectroscopy (fNIRS) to measure the hemodynamic response on the forehead
      during three trials of a cold pressor test (CPT) in 20 adults. To measure
      hemodynamic changes at the superficial tissues as well as the intracranial
      tissues, two configurations of 'far' and 'near' source-detector separations were
      used. We identified two features that were found to be fairly consistent across
      all subjects. The first feature was the change of total hemoglobin (THb)
      concentration in a given condition divided by the duration of that condition
      [Formula: see text]. Statistical analyses revealed that during the first CPT
      trial [Formula: see text] significantly changed from its baseline value in all
      channels. Also, adaptation to repeated CPTs was observed in both [Formula: see
      text] parameter and the reported post-stimulus pain rating scores. The second
      feature was the difference between the maximum and the minimum of the evoked
      changes in the THb concentration (DeltaTHb). A significant correlation was
      observed between the post-stimulus pain rating score and DeltaTHb at all
      channels. An asymmetrical activity was observed only at the 'far' channels. These
      results suggest that fNIRS can potentially be used as a reliable technique for
      the assessment of the hemodynamic response to tonic pain induced by the CPT.

PMID- 22956156
TI  - The extracellular matrix modulates fibroblast phenotype and function in the
      infarcted myocardium.
AB  - Cardiac fibroblasts are key cellular effectors of cardiac repair; their phenotype
      and function are modulated by interactions with extracellular matrix proteins.
      This review manuscript discusses the effects of the extracellular matrix on the
      inflammatory and reparative properties of fibroblasts in the infarcted
      myocardium. Early generation of matrix fragments in the infarct induces a pro
      inflammatory and matrix-degrading fibroblast phenotype. Formation of a
      fibrin/fibronectin-rich provisional matrix serves as a conduit for migration of
      fibroblasts into the infarcted area. Induction of ED-A fibronectin and
      nonfibrillar collagens may contribute to myofibroblast transdifferentiation.
      Upregulation of matricellular proteins promotes transduction of growth factor and
      cytokine-mediated signals. As the scar matures, matrix cross-linking, clearance
      of matricellular proteins, and reduced growth factor signaling cause deactivation
      and apoptosis of reparative infarct fibroblasts. Understanding the effects of
      matrix components on infarct fibroblasts may guide the design of peptides that
      reproduce, or inhibit, specific matricellular functions, attenuating adverse
      remodeling.

PMID- 22956157
TI  - TNF-alpha blocker therapy and solid malignancy risk in ANCA-associated
      vasculitis.
AB  - ANCA-associated vasculitides (AAV) are small vessel systemic vasculitis syndromes
      associated with the potential for high morbidity and mortality. This group
      includes granulomatosis with polyangiitis (Wegener's, GPA), microscopic
      polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg
      Strauss, EGPA). The standard treatment consists of a combination of
      glucocorticoids and potent immunosuppressant drugs. These have broad mechanisms
      of action as well as important adverse effects. Efforts have been made to
      investigate novel agents with better-defined and narrower mechanisms of action,
      such as biologics, including TNF-alpha blockers. Etanercept, a well-known TNF
      alpha blocker evaluated for GPA in the Wegener's Granulomatosis Etanercept Trial
      (WGET), was associated with an increase in the development of solid malignancies
      in comparison to placebo during that trial period. A 5-year follow-up after the
      WGET trial showed a sustained increase in incidence of solid malignancies, but
      this could no longer be solely attributed to etanercept exposure. These studies
      raised concerns about the use of the family of TNF-alpha blockers in AAV. Here,
      we review the evidence about the association between therapeutic inhibition of
      tumor necrosis factor (TNF-alpha) by etanercept and other TNF-alpha blockers with
      the development of solid malignancies in GPA and other AAV.

PMID- 22956160
TI  - Adaptive fractal analysis reveals limits to fractal scaling in center of pressure
      trajectories.
AB  - Fractal time series analysis methods are commonly used for analyzing center of
      pressure (COP) signals with the goal of revealing the underlying neuromuscular
      processes for upright stance control. The use of fractal methods is often coupled
      with the assumption that the COP is an instance of fractional Gaussian noise
      (fGn) or fractional Brownian motion (fBm). Our purpose was to evaluate the
      applicability of the fGn-fBm framework to the COP in light of several
      characteristics of COP signals revealed by a new method, adaptive fractal
      analysis (AFA). AFA quantifies how the variance of the residuals to fits of a
      globally smooth trend signal scales with the time scale at which the fits are
      performed. Application of AFA to COP signals revealed that there are potentially
      three fractal scaling regions in the COP as opposed to one as expected from a
      pure fGn or fBm process. The scaling region at the fastest scale was anti
      persistent and spanned ~30-90 ms, the intermediate was persistent and spanned
      ~200 ms-1.9 s, and the slowest was anti-persistent and spanned ~5-40 s. The
      intermediate fractal scaling region was the most clearly defined, but it only
      contributed around 11% of the total spectral energy of the COP signal, indicating
      that other features of the COP signal contribute more importantly to the overall
      dynamics. Also, more than half of the Hurst exponents estimated for the
      intermediate region were greater than the theoretically expected range [0,1] for
      fGn-fBm processes. These results suggest the fGn-fBm framework is not appropriate
      for modeling COP signals. ON-OFF intermittency might provide a better modeling
      framework for the COP, and multiscale approaches may be more appropriate for
      analyzing COP data.

PMID- 22956161
TI  - A topographically modified substrate-embedded MEA for directed myotube formation
      at electrode contact sites.
AB  - Myoblast fusion into functionally distinct myotubes, and their subsequent
      integration with the nervous system, is a poorly understood phenomenon with
      important applications in basic science research, skeletal muscle tissue
      engineering, and cell-based biosensor development. We have previously
      demonstrated the ability of microelectrode arrays (MEAs) to record the
      extracellular action potentials of myotubes, and we have shown that this
      information reveals the presence of multiple, electrophysiologically independent
      myotubes even in unstructured cultures where there is extensive physical contact
      between cells (Langhammer et al., Biotechnol Prog 27:891-895, 2011). In this
      paper, we explore the ability of microscale topographical trenches to guide the
      myoblast alignment and fusion processes and use our findings to create a
      substrate-embedded MEA containing topographical trenches that are able to direct
      myotube contractility to specific locations. By combining substrate-embedded MEA
      technology with topographical patterns, we have developed a lab-on-a-chip test
      bed for the non-invasive examination of myotubes.

PMID- 22956162
TI  - Getting your research out there: open access & more.

PMID- 22956163
TI  - Spatiotemporal mechanical variation reveals critical role for rho kinase during
      primitive streak morphogenesis.
AB  - Large-scale morphogenetic movements during early embryo development are driven by
      complex changes in biochemical and biophysical factors. Current models for
      amniote primitive streak morphogenesis and gastrulation take into account
      numerous genetic pathways but largely ignore the role of mechanical forces. Here,
      we used atomic force microscopy (AFM) to obtain for the first time precise
      biomechanical properties of the early avian embryo. Our data reveal that the
      primitive streak is significantly stiffer than neighboring regions of the
      epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test
      our hypothesis that these changes in mechanical properties are due to a localized
      increase of actomyosin contractility, we inhibited actomyosin contractility via
      the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our
      results using several different assays show the following: (1) primitive streak
      formation was blocked; (2) the time-dependent increase in primitive streak
      stiffness was abolished; and (3) convergence of epiblast cells to the midline was
      inhibited. Taken together, our data suggest that actomyosin contractility is
      necessary for primitive streak morphogenesis, and specifically, ROCK plays a
      critical role. To better understand the underlying mechanisms of this fundamental
      process, future models should account for the findings presented in this study.

PMID- 22956164
TI  - Gait variability is altered in older adults when listening to auditory stimuli
      with differing temporal structures.
AB  - Gait variability in the context of a deterministic dynamical system may be
      quantified using nonlinear time series analyses that characterize the complexity
      of the system. Pathological gait exhibits altered gait variability. It can be
      either too periodic and predictable, or too random and disordered, as is the case
      with aging. While gait therapies often focus on restoration of linear measures
      such as gait speed or stride length, we propose that the goal of gait therapy
      should be to restore optimal gait variability, which exhibits chaotic
      fluctuations and is the balance between predictability and complexity. In this
      context, our purpose was to investigate how listening to different auditory
      stimuli affects gait variability. Twenty-seven young and 27 elderly subjects
      walked on a treadmill for 5 min while listening to white noise, a chaotic rhythm,
      a metronome, and with no auditory stimulus. Stride length, step width, and stride
      intervals were calculated for all conditions. Detrended Fluctuation Analysis was
      then performed on these time series. A quadratic trend analysis determined that
      an idealized inverted-U shape described the relationship between gait variability
      and the structure of the auditory stimuli for the elderly group, but not for the
      young group. This proof-of-concept study shows that the gait of older adults may
      be manipulated using auditory stimuli. Future work will investigate which
      structures of auditory stimuli lead to improvements in functional status in older
      adults.

PMID- 22956165
TI  - Treatment and return to sport following a Jones fracture of the fifth metatarsal:
      a systematic review.
AB  - PURPOSE: The aim of this study is to better inform the sports surgeon of current
      evidence for the treatment of Jones fractures of the base of the 5th metatarsal.
      The study aimed to establish what the outcomes were for different treatments
      modalities. By doing this, the clinician will be better prepared to institute a
      logical, evidence-based approach to the treatment of their patients with this
      injury. METHODS: A thorough literature search was performed from 1980 to present
      day. Studies were included based on set criteria and analysed for their validity,
      and their results were scrutinised. Jones fractures were segregated into acute
      fractures, delayed unions and non-unions. RESULTS: Twenty-six studies were
      included, of which 22 were level 4 evidence, with only 1 randomised controlled
      trial. Functional outcome data were limited to return to sports in most studies
      with few studies using established scoring systems. Return to sports following
      intra-medullary screw fixation for acute fractures ranged from 4 to 18 weeks.
      Acute fractures treated non-operatively had a union rate of 76 % (pooled),
      whereas in fractures treated with a screw it was 96 % (pooled). Delayed unions
      treated non-operatively had a union rate of 44 and 97 % treated operatively. Non
      unions treated with screw fixation healed in 97 % of cases. CONCLUSIONS: Although
      supported by mostly level 4 evidence, intra-medullary screw fixation is more
      likely to lead to successful union of all types of Jones fractures compared to
      non-operative treatments. Early return to play in athletes prior to full
      radiological union is not advised in case of re-fracture.

PMID- 22956166
TI  - Measurement of lateral plateau depression and lateral plateau widening in a
      Schatzker type II fracture can predict a lateral meniscal injury.
AB  - PURPOSE: The purpose of this study is to determine the plain radiographic signs
      that can be indicative of meniscal injuries in Schatzker type II tibial plateau
      fractures. METHODS: The lateral plateau depression and lateral plateau widening
      were measured on anteroposterior knee radiographs in 20 patients with Schatzker
      type II tibial plateau fracture. Meniscal injury was present in 12 patients
      (three, meniscal tears; nine, peripheral meniscal detachments). The lateral
      plateau depression and lateral plateau widening measurements were compared
      between those who had meniscal injury (Group 1) and those who did not (Group 2).
      RESULTS: In Group 1, the median lateral plateau depression was 20 mm (IQR: 14-25)
      and the median lateral plateau widening was 12 mm (IQR: 10-14). In Group 2, the
      respective values were 10 mm (IQR: 5-17) and 6 mm (IQR: 2-10). There was a
      statistically significant difference in both parameters when the two groups were
      compared (p = 0.001). CONCLUSIONS: A plain anteroposterior radiograph depicting a
      lateral plateau depression >=14 mm and/or a lateral plateau widening >=10 mm is
      associated with a significantly increased risk of meniscal injury in Schatzker
      type II tibial plateau fractures. These parameters can be used to predict the
      probable presence of lateral meniscal injury in such patients in routine clinical
      practice. LEVEL OF EVIDENCE: Retrospective comparative study, level III.

PMID- 22956167
TI  - Comparison of patient satisfaction with two different etanercept delivery
      systems. A randomised controlled study in patients with rheumatoid arthritis.
AB  - The objective of this study was to investigate patients' perceptions of the
      acceptability of two devices delivering etanercept for rheumatoid arthritis (RA)
      treatment and to explore whether specific patients' attributes are associated
      with device preferences. Two similar multicenter, open-label, randomised,
      parallel-design studies were conducted in a total of 13 European countries. A
      total of 640 adult patients with RA were randomised to receive etanercept 50 mg
      once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a
      pre-filled pen (PFP). Patient satisfaction at week 12 was measured on a 0- to 10
      point Likert scale (primary endpoint). The study was powered to demonstrate non
      inferiority of a PFP over PFS for the primary endpoint. At week 12, mean patient
      satisfaction was 8.3 (+/- 2.4) points in the pen group and 7.2 (+/- 2.6) points
      in the syringe group. Non-inferiority and even superiority of the pen over the
      syringe was demonstrated. In conclusion, this study showed higher patient
      satisfaction in the group of patients injecting etanercept with a PFP compared
      with the group of patients using a PFS.

PMID- 22956168
TI  - [Secondary vasculitides and vasculitis mimics].
AB  - Secondary vasculitis is a form of vasculitis for which an underlying disease is
      known. Diseases associated with secondary vasculitis include infections, drug
      hypersensitivity, malignancy, rheumatoid arthritis, collagen vascular disease and
      sarcoidosis. Moreover, there are numerous conditions that can mimic vasculitis
      clinically, in laboratory testing, radiographically and in histopathology. It is
      evident that distinguishing primary vasculitis from secondary vasculitis and also
      vascular inflammation from non-vasculitic disorders (vasculitis mimics) has
      significant therapeutic implications.

PMID- 22956169
TI  - Protein antigen adsorption to the DDA/TDB liposomal adjuvant: effect on protein
      structure, stability, and liposome physicochemical characteristics.
AB  - PURPOSE: Understanding the nature of adjuvant-antigen interactions is important
      for the future design of efficient and safe subunit vaccines, but remains an
      analytical challenge. We studied the interactions between three model protein
      antigens and the clinically tested cationic liposomal adjuvant composed of
      dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB). METHODS:
      The effect of surface adsorption to DDA/TDB liposomes on colloidal stability and
      protein physical stability/secondary structure was investigated by dynamic light
      scattering, circular dichroism, Fourier transform infrared spectroscopy and
      differential scanning calorimetry. RESULTS: Bovine serum albumin and ovalbumin
      showed strong liposome adsorption, whereas lysozyme did not adsorb. Upon
      adsorption, bovine serum albumin and ovalbumin reduced the phase transition
      temperature and narrowed the gel-to-liquid phase transition of the liposomes
      implying interactions with the lipid bilayer. The protein-to-lipid ratio
      influenced the liposome colloidal stability to a great extent, resulting in
      liposome aggregation at intermediate ratios. However, no structural alterations
      of the model proteins were detected. CONCLUSIONS: The antigen-to-lipid ratio is
      highly decisive for the aggregation behavior of DDA/TDB liposomes and should be
      taken into account, since it may have an impact on general vaccine stability and
      influence the choice of analytical approach for studying this system,
      also/especially at clinically relevant protein-to-lipid ratios.

PMID- 22956170
TI  - Characterization of therapeutic monoclonal antibodies reveals differences between
      in vitro and in vivo time-course studies.
AB  - PURPOSE: To examine and determine the sites and the kinetics of IgG1 mAb
      modifications from both in vitro (rat plasma and PBS) and in vivo (rat model)
      time-course studies. METHODS: A comprehensive set of protein characterization
      methods, including RPLC/MS, LC-MS/MS, iCIEF, capSEC, and CE-SDS were performed in
      this report. RESULTS: We demonstrate that plasma incubation and in vivo
      circulation increase the rate of C-terminal lysine removal, and the levels of
      deamidation, pyroglutamic acid (pyroE), and thioether-linked (lanthionine) heavy
      chain and light chain (HC-S-LC). In contrast, incubation in PBS shows no C
      terminal lysine removal, and slower rates of deamidation, pyroE, and HC-S-LC
      formation. Other potential modifications such as oxidation, aggregation, and
      peptide bonds hydrolysis are not enhanced. CONCLUSION: This study demonstrates
      that in vivo mAb modifications are not fully represented by in vitro PBS or
      plasma incubation. The differences in modifications and their rates reflect the
      dissimilarities of matrices and the impact of enzymes. These observations provide
      valuable evidence and knowledge in evaluating the criticality of modifications
      that occur naturally in vivo that might impact formulation design, therapeutic
      outcome, and critical quality attribute assessments for therapeutic mAb
      manufacturing and quality control.

PMID- 22956171
TI  - Continuous generation of ethyl cellulose drug delivery nanocarriers from
      microbubbles.
AB  - PURPOSE: To investigate a new microfluidic method for the continuous preparation
      of hollow-shell nanoparticles of a hydrophobic polymer and the simultaneous
      encapsulation within these of a hydrophilic active pharmaceutical ingredient.
      METHOD: A specially designed and constructed microfluidic device which
      facilitates at a junction the impingement of two liquids flowing in capillaries
      kept 60 degrees  apart, one containing the polymer ethyl cellulose (EC) and the
      other active pharmaceutical ingredient amoxicillin, and a gas flowing in a
      capillary bisecting the two liquid flows, was used to continuously generate EC
      coated microbubbles at an outlet directly below the gas flow. The bubbles produce
      EC nanoparticles whilst encapsulating amoxicillin, and these were characterised
      by microscopy, zeta potential measurements, FTIR and UV spectroscopy and in vitro
      drug release and kinetic studies. RESULTS: The device produced ~5 * 10(6)
      microbubbles per minute from the surface of which EC nanocarriers were released
      spontaneously according to an evaporation-controlled mechanism. The gas pressure
      was very effective in controlling the size and size distribution of the
      nanocarriers. CONCLUSIONS: Nanocarriers with diameter between 10 and 800 nm were
      continuously produced by controlling the gas pressure between 110 and 510 kPa.
      Depending on their size, particles were capable of encapsulating 65-88% of
      amoxicillin which was released over ~12 h.

PMID- 22956172
TI  - Regulatory regions of the paraoxonase 1 (PON1) gene are associated with
      neovascular age-related macular degeneration (AMD).
AB  - Physiological stress response and oxidative damage are factors for aging
      processes and, as such, are thought to contribute to neovascular age-related
      macular degeneration (AMD). Paraoxonase 1 (PON1) is an enzyme that plays an
      important role in oxidative stress and aging. We investigated association of DNA
      sequence variants (SNP) within the upstream regulatory region of the PON1 gene
      with neovascular AMD in 305 patients and 288 controls. Four of the seven tested
      SNPs (rs705379, rs705381, rs854573, and rs757158) were more frequently found in
      AMD patients compared to controls (P = 0.0099, 0.0295, 0.0121, and 0.0256,
      respectively), and all but one (SNP rs757158) are in linkage disequilibrium.
      Furthermore, haplotype TGGCCTC conferred protection (odds ratio (OR) = 0.76, (CI)
      = 0.60-0.97) as it was more frequently found in control individuals, while
      haplotype CGATGCT increased the risk (OR = 1.55, CI = 1.09-2.21) for AMD. These
      results were also reflected when haplotypes for the untranscribed and the
      5'untranslated regions (5'UTR) were analyzed separately. To assess haplotype
      correlation with levels of gene expression, the three SNPs within the 5'UTR were
      tested in a luciferase reporter assay. In retinal pigment epithelium-derived
      ARPE19 cells, we were able to measure significant differences in reporter levels,
      while this was not observed in kidney-derived HEK293 cells. The presence of the
      risk allele A (SNP rs705381) caused an increase in luciferase activity of
      approximately twofold. Our data support the view that inflammatory reactions
      mediated through anti-oxidative activity may be relevant to neovascular age
      related macular degeneration.

PMID- 22956173
TI  - Immature dendritic cell-derived exosomes: a promise subcellular vaccine for
      autoimmunity.
AB  - Exosomes, 60-90-nm-sized vesicles, are produced by a large number of cell types,
      including tumor cells, neurons, astrocytes, hemocytes, intestinal epithelial
      cells, and so on. Dendritic cell (DC), the most potent professional antigen
      presenting cell in the immune system, produces exosomes in the course of
      maturation. Mature DCs produce exosomes with the ability to elicit potent
      immunoactivation, resulting in tumor eradication and bacterial or virus
      elimination. Given the notion that exosomes are stable and easy to be modified
      artificially, autologous mature DC-derived exosomes have been vaccinated into
      patients with malignant diseases. In clinical trials utilizing exosomes as
      therapeutic approaches, researchers observed considerable curative effect with
      little side effect. However, immature or suppressive DC-derived exosomes harbor
      anti-inflammatory properties distinct from mature DC-derived exosomes. In murine
      models of autoimmune disease and transplantation, immature DC-derived exosomes
      reduced T cell-dependent immunoactivation, relieved clinical manifestation of
      autoimmune disease, and prolonged survival time of transplantation. Although the
      exact mechanism of how immature DC-derived exosomes function in vivo is still
      unclear, and there are no clinical trials regarding application of exosome
      vaccine into patients with autoimmune disease, we will analyze the promise of
      immature DC-derived exosomes as a subcellular vaccine in autoimmunity in this
      review.

PMID- 22956174
TI  - High Ran level is correlated with poor prognosis in patients with colorectal
      cancer.
AB  - BACKGROUND: The Ras-like nuclear protein (Ran) is involved in the regulation of
      nuclear transport, microtubule nucleation and dynamics, and spindle assembly. Its
      fundamental function is nucleocytoplasmic transport of RNA and proteins. The
      expression and potential role of Ran in colorectal cancer (CRC) remain unclear.
      The aim of this study was to investigate the relationship between Ran expression
      and CRC characteristics. The potential role of Ran as a prognostic indicator was
      also evaluated. METHODS: We used immunohistochemistry and western blotting to
      detect Ran expression in 287 CRC tissues. The relationships between Ran
      expression and clinicopathological characteristics and overall survival rate were
      statistically analyzed. RESULTS: CRC tissues had significantly higher Ran
      expression than normal colorectal epithelial cells. Ran was positively correlated
      with depth of invasion, lymph node metastases, distant metastases, tumor
      differentiation, and tumor-node-metastasis stage. However, no correlation was
      found between Ran expression and patient age or sex. The overall survival rate
      was consistently and significantly lower in patients with Ran-positive tumors
      than in those with Ran-negative tumors. CONCLUSION: Our findings emphasize the
      important role of Ran in differentiation, disease stage, and metastasis in human
      CRC. Ran may play an important role in the development of CRC and may serve as a
      novel prognostic indicator of CRC.

PMID- 22956175
TI  - Resection of the inferior vena cava for urological malignancies: single-center
      experience.
AB  - BACKGROUND: Resection of the inferior vena cava (IVC) is occasionally performed
      for patients with advanced malignancy in the retroperitoneum. In the current
      study, we assessed the oncological effectiveness of IVC resection combined with
      tumor resection. We also addressed peri- and postoperative complications
      associated with resection and reconstruction of the IVC. METHODS: Between 1984
      and 2011, a total of 23 patients underwent caval resection concurrently with
      retroperitoneal tumor excision. Primary tumor histology was renal cell carcinoma
      in 19 patients, metastatic germ cell tumor in 2, and leiomyosarcoma, and adrenal
      cancer in 1 patient each. Clinicopathological data from these patients were
      retrospectively reviewed. RESULTS: IVC reconstruction was performed by direct
      suture in 11 patients, patch repair in 8 and graft replacement in 3 patients.
      Interruption of the IVC was performed in one patient. There was no lethal
      complication or pulmonary embolism. Intracaval thrombosis, although patent, was
      observed in four patients after surgery. All patients underwent infrarenal IVC
      reconstruction. The median follow-up was 12 months (range 1-121 months). Of the
      20 patients without distant metastasis at the time of surgery, complete resection
      was achieved in 14, whereas 6 patients had positive margins. Although nine
      patients developed distant metastases postoperatively, there was no local
      recurrence. The overall survival, progression-free survival and cause-specific
      survival in those RCC patients without distant metastasis at the time of surgery
      were 56.1, 47.0 and 60.4%, respectively, at 5 years. CONCLUSIONS: For advanced
      malignancies involving the IVC, resection is a safe and feasible procedure for
      selected patients.

PMID- 22956176
TI  - 782 consecutive construction work accidents: who is at risk? A 10-year analysis
      from a Swiss university hospital trauma unit.
AB  - BACKGROUND: Mortality and morbidity are particularly high in the building
      industry. The annual rate of non-fatal occupational accidents in Switzerland is
      1,133 per 100,000 inhabitants. METHODS: Retrospective analysis of the electronic
      database of a university emergency centre. Between 2001 and 2011, 782
      occupational accidents to construction workers were recorded and analysed using
      specific demographic and medical keywords. RESULTS: Most patients were aged 30-39
      (30.4%). 66.4% of the injured workers were foreigners. This is almost twice as
      high as the overall proportion of foreigners in Switzerland or in the Swiss
      labour market. 16% of the Swiss construction workers and 8% of the foreign
      construction workers suffered a severe injury with ISS >15. There was a trend for
      workers aged 60 and above to suffer an accident with a high ISS (p = 0.089).
      CONCLUSIONS: As in other European countries, most patients were in their
      thirties. Older construction workers suffered fewer injuries, although these
      tended to be more severe. The injuries were evenly distributed through the
      working days of the week. A special effort should be made that current health and
      safety measures are understood and applied by foreign and older construction
      workers.

PMID- 22956178
TI  - Doppler US measurement of the superior mesenteric artery blood flow in children
      and adolescents.
AB  - BACKGROUND: Blood flow volume in the superior mesenteric artery (SMA) measured by
      pulsed Doppler has been used in adults to evaluate Crohn disease but has not been
      utilized in children and adolescents. OBJECTIVE: To establish a cutoff point for
      normal SMA blood flow using pulsed Doppler US measurement in healthy children and
      adolescents. MATERIALS AND METHODS: The study included healthy volunteers from an
      urban community, divided into two age groups, children (5-9 years) and
      adolescents (10-17 years). Anthropometric measurements included waist
      circumference and body surface area classified according to the z-score of body
      mass index. Heart rate, blood pressure, oxygen saturation and temperature were
      measured immediately before US evaluation. RESULTS: The average age of the 60
      participants was 12.2 years. Of these, 21 (35%) were ages 5-9 years and 39 (65%)
      were ages 10-17 years; 21 (35%) were boys. Findings of the two examiners
      coincided for 58 of the 60 (96.7%) participants. SMA blood flow was significantly
      lower in the children (mean +/- SD = 556 +/- 122 ml/min) than in adolescents
      (mean +/- SD 775 +/- 311 ml/min) (P < 0.001). SMA blood flow showed statistically
      significant positive associations with body surface area. CONCLUSION: We found
      that superior mesenteric artery blood flow is significantly lower in children
      than in adolescents and is associated with body surface area.

PMID- 22956179
TI  - Prevalence of radiographic semicircular canal dehiscence in very young children:
      an evaluation using high-resolution computed tomography of the temporal bones.
AB  - BACKGROUND: Previous studies suggest that semicircular canal dehiscences (SCDs)
      have a developmental origin. OBJECTIVE: We hypothesized that if SCDs originate
      during development, incidence of radiographic SCDs in young children will be
      higher than in adults. MATERIALS AND METHODS: Thirty-four temporal bone HRCTs of
      children younger than 2 years and 40 temporal bone HRCTs of patients older than
      18 years were reformatted and re-evaluated for presence of SCD or canal thinning.
      Results were compared with indications for HRCT and clinical information.
      RESULTS: SCDs were detected in 27.3% of children younger than 2 years of age
      (superior, 13.8%; posterior, 20%) and in 3% of adults (P < 0.004). Of children
      with one radiographic dehiscence, 55.6% had multiple and 44% had bilateral SCDs
      on HRCT. No lateral canal SCDs were present. Thinning of bone overlying the
      semicircular canals was found in 44% of children younger than 2 years and 2.5% of
      adults (P < 0.0001). CONCLUSION: SCDs are more common on HRCTs of very young
      children. This supports the hypothesis that SCDs originate from discontinuation
      of bone deposition/maturation. However, SCDs on imaging do not necessarily
      correlate with canal dehiscence syndrome and should therefore be interpreted
      carefully.

PMID- 22956181
TI  - Improving the selectivity of the phosphoric acid beta-elimination on a
      biotinylated phosphopeptide.
AB  - This study aims at improving the MALDI-TOF detection of a phosphorylated peptide
      containing a cysteine residue by beta-elimination of H(3)PO(4) hardly enriched by
      classical methods. The experimental conditions were optimized on this
      phosphopeptide (biot-pAdd) and its nonphosphorylated counterpart (biot-Add). The
      major side-reactions were H(2)S elimination on the cysteine residues and H(2)O
      elimination on the non phosphorylated serine residue of biot-Add. The former
      dilutes the MALDI-TOF signal for the desired species. The latter gives a product
      similar to what is obtained by H(3)PO(4) elimination and should prompt to caution
      when working with a mixture between phosphorylated and non phosphorylated
      peptides. Modifications on the solvent, the reaction temperature and time, the
      nature, and concentration of the base were made. Major improvement of the
      selectivity of the reaction was observed in 30 % ACN, at room temperature for 4
      h. However, these optimizations are specific to these sequences and should be
      performed anew for different peptides. The selectivity of the reaction towards
      H(3)PO(4) elimination is improved, but the persistence of side-reactions renders
      a previous sample fractionation necessary. In these optimized conditions, the
      ionization enhancement is 3-fold and the detection limits for biot-pAdd are
      similar to biot-Add (100 fmol).

PMID- 22956182
TI  - Anemia and activities of daily living in the Korean urban elderly population:
      results from the Korean Longitudinal Study on Health and Aging (KLoSHA).
AB  - This study was planned to investigate the prevalence and risk factors of anemia
      and its impact on health-related quality of life and activities of daily living
      (ADL) in elderly Koreans. Of the 1,118 randomly sampled elderly Koreans aged 65
      years or older living in Seongnam, Korea, on Aug. 1, 2005, we estimated the
      prevalence of anemia from 695 responders. We investigated the risk factors of
      anemia using a merged sample of this random sample and 270 volunteers enrolled
      from Seongnam residents aged 85 years or older. We diagnosed anemia according to
      the World Health Organization criteria. The estimated age- and gender
      standardized prevalence of anemia was 8.33 % for the overall random sample (95 %
      confidence intervals (CI) 6.28-10.39), 10.58 % in men (95 % CI 7.09-14.07), and
      6.85 % in women (95 % CI 4.37-9.34). The identified risk factors were age >=80
      years, male, iron deficiency, history of stroke, renal dysfunction, and metabolic
      syndrome. Anemia was associated with impairment in physical functioning (p =
      0.031) and instrumental ADL (p < 0.001). This is the first report about anemia's
      prevalence in community-dwelling Korean elders, adjusted and standardized
      according to the city's and nation's population. Timely diagnosis of anemia and
      correction of its treatable cause may improve QOL and ADL in elderly individuals.

PMID- 22956183
TI  - The use of CD138 positively selected marrow samples increases the applicability
      of minimal residual disease assessment by PCR in patients with multiple myeloma.
AB  - We have evaluated the use of CD138+ positively selected bone marrow samples to
      identify a molecular target for minimal residual disease assessment by polymerase
      chain reaction (PCR) in 25 untreated patients with multiple myeloma. A fraction
      of each sample was used for CD138+ selection, and the rest served as a reference
      control. VDJH, DJH, and Kde gene rearrangements were tested for amplification
      according to the BIOMED-2 Concerted Action. PCR products were directly sequenced
      in an automated ABI 3130 DNA sequencer using Big-Dye terminators. Within the
      CD138+ selected group, VDJH rearrangements were detected in all cases (100 %),
      DJH in 16 (64 %), and Kde in 18 (72 %) cases; whereas in the control samples,
      VDJH, DJH, and Kde rearrangements were detected in 19 (76 %), 11 (44 %), and 12
      (48 %) cases, respectively. After sequencing, 24 (96 %) cases within the CD138+
      group had a PCR target for MRD detection compared with 15 (60 %) cases in the
      control group. We conclude that the use of CD138+ positively selected bone marrow
      samples increases the applicability of minimal residual disease studies by PCR in
      patients with multiple myeloma.

PMID- 22956184
TI  - Study of methylation of histone H3 lysine 9 and H3 lysine 27 during X chromosome
      inactivation in three types of cells.
AB  - Histone methylation is one epigenetic modification of an inactive X chromosome
      (Xi). Histone H3 lysine 9 dimethylation (H3K9me) and histone H3 lysine 27
      trimethylation (H3K27me) are both associated with the chromatin of gene-silenced
      regions in the X chromosome and with X inactivation. Studies have shown that
      H3K9me is supposedly an early mark on the X chromosome during inactivation. Here,
      we examined the distribution and enrichment profiles of H3K9me and H3K27me by
      indirect immunofluorescence. We found that H3K9me appears to have a broad
      distribution throughout the whole genome, but is specific, to a certain extent,
      to the Xi in WI38 cells. In contrast, H3K27me is highly specific to the entire
      Xi, which differs significantly from other areas of the nucleus. Thus, H3K27me is
      more suitable as an epigenetic mark than H3K9me. The chromatin
      immunoprecipitation analyses also showed that H3K27me predominates on the
      inactive genes of the X chromosome. Additionally, we compared the levels of
      H3K9me and H3K27me in four X-linked genes and two autosomal genes between the
      normal cells (WI38) and the tumor cells (HeLa). The results revealed that the
      methylation levels of the inactive genes (POLA and OCRL) in tumor cells (HeLa)
      were lower than those in normal cells (WI38) and that the methylation levels of
      the Xi inactivation-avoidance genes (SMCX and ZFX) and autosomal genes (Myc and
      beta-actin) varied widely in tumor cells (HeLa). These events may be significant
      for cancer cell development and contribute to the characteristics of tumor cells.

PMID- 22956185
TI  - What will be the role of I-123 MIBG in improving the outcome of medically treated
      heart failure patients?

PMID- 22956186
TI  - Notch signaling regulates tumor-induced angiogenesis in SPARC-overexpressed
      neuroblastoma.
AB  - Despite existing aggressive treatment modalities, the prognosis for advanced
      stage neuroblastoma remains poor with significant long-term illness in disease
      survivors. Advance stage disease features are associated with tumor vascularity,
      and as such, angiogenesis inhibitors may prove useful along with current
      therapies. The matricellular protein, secreted protein acidic and rich in
      cysteine (SPARC), is known to inhibit proliferation and migration of endothelial
      cells stimulated by growth factors. Here, we sought to determine the effect of
      SPARC on neuroblastoma tumor cell-induced angiogenesis and to decipher the
      molecular mechanisms involved in angiogenesis inhibition. Conditioned medium from
      SPARC-overexpressed neuroblastoma cells (pSPARC-CM) inhibited endothelial tube
      formation, cell proliferation, induced programmed cell death and suppressed
      expression of pro-angiogenic molecules such as VEGF, FGF, PDGF, and MMP-9 in
      endothelial cells. Further analyses revealed that pSPARC-CM-suppressed expression
      of growth factors was mediated by inhibition of the Notch signaling pathway, and
      cells cultured on conditioned medium from tumor cells that overexpress both Notch
      intracellular domain (NICD-CM) and SPARC resumed the pSPARC-CM-suppressed
      capillary tube formation and growth factor expression in vitro. Further, SPARC
      overexpression in neuroblastoma cells inhibited neo-vascularization in vivo in a
      mouse dorsal air sac model. Furthermore, SPARC overexpression-induced endothelial
      cell death was observed by co-localization studies with TUNEL assay and an
      endothelial marker, CD31, in xenograft tumor sections from SPARC-overexpressed
      mice. Our data collectively suggest that SPARC overexpression induces endothelial
      cell apoptosis and inhibits angiogenesis both in vitro and in vivo.

PMID- 22956187
TI  - The use of high dose d,l-leucovorin in first-line bevacizumab+mFOLFIRI treatment
      of patients with metastatic colorectal cancer may enhance the antiangiogenic
      effect of bevacizumab.
AB  - The role of d,l-leucovorin (d,l-LV) dose on efficacy and toxicity of first-line
      bevacizumab+mFOLFIRI or mFOLFIRI treatment has never been investigated in
      patients with metastatic colorectal cancer. This study was an investigator
      initiated retrospective observational investigation performed on 450 consecutive
      patients. The mFOLFIRI regimen consisted of irinotecan (180 mg/m(2)), d,l-LV low
      (200 mg/m(2)) or high (400 mg/m(2)) dose and bolus 5-fluorouracil (5-FU) (400
      mg/m(2)), followed by a 46-h infusion of 5-FU (2400 mg/m(2)). The
      bevacizumab+mFOLFIRI regimen consisted of bevacizumab (5 mg/kg)+mFOLFIRI. The
      efficacy (objective response [OR], progression-free [PFS] and overall survival
      [OS]) and toxicity was evaluated and compared. The use of high versus low dose
      d,l-LV in bevacizumab+mFOLFIRI regimen improved the OR rate (63 and 38 %,
      respectively; P = 0.00015), median PFS (13 and 9 months, respectively; P =
      0.000005) and median OS (26 and 21 months, respectively; P = 0.0058). The
      efficacy of mFOLFIRI and the toxicity pattern of both bevacizumab+mFOLFIRI and
      mFOLFIRI regimens were independent of d,l-LV dose. Beside the d,l-LV dose the
      bevacizumab-related hypertension was an independent marker of longer survival.
      The use of high d,l-LV dose in bevacizumab+mFOLFIRI regimen would enhance the
      antiangiogenic effect of bevacizumab and subsequently the efficacy of treatment
      without increasing the number of adverse events. These findings need to be
      further confirmed in a randomized controlled prospective trial.

PMID- 22956188
TI  - The combined effect of sleep deprivation and Western diet on spatial learning and
      memory: role of BDNF and oxidative stress.
AB  - Either sleep deprivation or Western diet can impair learning and memory via
      induction of oxidative stress, which results in neuronal damage and interference
      with the neurotransmission. In this study, we examined the combined effect of
      sleep deprivation and Western diet on hippocampus-dependent spatial learning and
      memory. In addition, possible molecular targets for sleep deprivation and Western
      diet-induced cognitive impairments were investigated. Sleep deprivation was
      induced in rats using the modified multiple platform model simultaneous with the
      administration of Western diet for 6 weeks. Thereafter, spatial learning and
      memory were tested using radial arm water maze. At the molecular level, BDNF
      protein and antioxidant markers including superoxide dismutase (SOD), catalase,
      glutathione peroxidase (GPx), glutathione (GSH), oxidized glutathione (GSSG),
      GSH/GSSG, and thiobarbituric acid reactive substances (TBARS) were assessed. The
      results of this study revealed that sleep deprivation, Western diet, or a
      combination of both impair short- and long-term memory (P < 0.05). The magnitude
      of the impairment induced by the combined treatment at the 24-h long-term memory
      was higher than that caused by each factor alone (P < 0.05). In addition, the
      combined treatment reduced the levels of hippocampal BDNF, a reduction that was
      not detected with each factor alone. Moreover, the combined treatment reduced the
      hippocampal activities of SOD, catalase, GPx, ratio of GSH/GSSG, and elevated
      TBARS level (P < 0.05). In conclusion, the combination of sleep deprivation and
      Western diet decreases BDNF levels and increases oxidative stress in the
      hippocampus, thus inducing memory impairment that is greater than the impairment
      produced by each factor alone.

PMID- 22956189
TI  - D-NAP prophylactic treatment in the SOD mutant mouse model of amyotrophic lateral
      sclerosis: review of discovery and treatment of tauopathy.
AB  - Davunetide (NAP) is a leading drug candidate being tested against tauopathy.
      Davunetide is an eight-amino-acid peptide fragment derived by structure-activity
      studies from activity-dependent neuroprotective protein, activity-dependent
      neuroprotective protein (ADNP). ADNP is essential for brain formation. ADNP
      haploinsufficiency in mice results in tauopathy and cognitive deficits
      ameliorated by davunetide treatment. This article summarizes in brief recent
      reviews about NAP protection against tauopathy including the all D-amino acid
      analogue-D-NAP (AL-408). D-NAP was discovered to have similar neuroprotective
      functions to NAP in vitro. Here, D-NAP was tested as prophylactic as well as
      therapeutic treatment for amytrophic lateral sclerosis (ALS) in the widely used
      TgN(SOD1-G93A)1Gur transgenic mouse model. Results showed D-NAP-associated
      prophylactic protection, thus daily treatment starting from day 2 of age resulted
      in a prolonged life course in the D-NAP-treated mice, which was coupled to a
      significant decrease in tau hyperphosphorylation. These studies correlate
      protection against tau hyperphosphorylation and longevity in a severe model of
      ALS-like motor impairment and early mortality. NAP is a first-in-class drug
      candidate/investigation compound providing neuroprotection coupled to inhibition
      of tau pathology. D-NAP (AL-408) is a pipeline product.

PMID- 22956190
TI  - Bisphosphonates in the treatment of patients with lung cancer and metastatic bone
      disease: a systematic review and meta-analysis.
AB  - PURPOSE: Bisphosphonates are known to prevent skeletal-related events (SREs) in
      advanced breast cancer, prostate cancer, and multiple myeloma. This systematic
      review assessed the efficacy of bisphosphonates in preventing SREs, controlling
      pain, and overall survival in patients with bone metastases from lung cancer.
      METHODS: We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library
      databases through November 10, 2011 for controlled trials that included lung
      cancer patients with bone metastases treated with bisphosphonates. Two reviewers
      independently extracted data on pain control, survival, and SREs and evaluated
      the quality of each study. Meta-analyses were performed when there were two or
      more trials with similar outcomes. RESULTS: Twelve trials met our inclusion
      criteria and included 1,767 patients. Studies were placebo-controlled, or had
      compared bisphosphonates with other modalities (chemotherapy, radiation therapy,
      or radioisotope therapy), or had used different bisphosphonates as active
      controls. Randomized controlled trials did not report adequate descriptions of
      randomization procedures, allocation concealment, and blinding, resulting in low
      quality scores. Patients treated with zoledronic acid + chemotherapy had fewer
      SREs than those receiving chemotherapy alone (relative risk (RR) 0.81, 95 %
      confidence interval (CI) 0.67-0.97). Pain control improved when a bisphosphonate
      was added to another treatment modality (chemotherapy or radiation; RR 1.18, 95
      %CI 1.0-1.4). Bisphosphonate therapy improved survival compared to controls, but
      the difference failed to reach statistical significance (mean of 72 days, 95 %CI 
      8.9 to 152.9). CONCLUSIONS: Treatment with bisphosphonates reduced SREs, improved
      pain control, and showed a trend to increased survival. Bisphosphonates should be
      used in the treatment of patients with lung cancer and bone metastases.

PMID- 22956191
TI  - Implementation of modified early-goal directed therapy for sepsis in the
      emergency center of a comprehensive cancer center.
AB  - PURPOSE: The investigation examines the impact of a standardized sepsis order set
      and algorithm utilizing non-invasive monitoring for early-goal directed therapy
      (EGDT) in an emergency center setting on the clinical outcomes of sepsis in
      cancer patients. METHODS: Single-center, retrospective study comparing clinical
      outcomes of sepsis before and after routine usage of a standardized order set and
      algorithm for non-invasive elements of EGDT for sepsis in an emergency center of
      a comprehensive cancer center. The outcomes measures evaluated were 28-day in
      hospital mortality, intensive care unit length of stay, hospital length of stay,
      goal mean arterial pressure and urine output within the first 6 h of treatment,
      time to measurement of lactic acid, and appropriateness and timeliness of initial
      antibiotic therapy. RESULTS: The 28-day in-hospital mortality was significantly
      lower in the post-intervention group compared to the pre-intervention group (20
      vs. 38%, p = 0.005). The percentages of patients who reached their goal mean
      arterial pressure (74 vs. 90%, p = 0.004) and goal urine output (79 vs. 96%, p =
      0.002) during the first 6 h of treatment were higher the after than the before
      group. No significant differences were detected in the rest of the outcome
      measures. CONCLUSIONS: Implementation of a standardized sepsis order set and
      algorithm to improve compliance with the non-invasive elements of EGDT for sepsis
      in cancer patients in the emergency center setting was associated with a
      decreased 28-day in-hospital mortality rate.

PMID- 22956192
TI  - Cancer caregivers' perceptions of an exercise and nutrition program.
AB  - PURPOSE: Little research has addressed exercise and nutrition-based interventions
      for cancer caregivers. This study explored cancer caregivers' perceptions of
      participating in a structured exercise and nutrition program alongside cancer
      survivors for whom they provided care. METHODS: In-depth, semi-structured
      interviews were conducted by one interviewer with 12 cancer caregivers about
      their experiences participating in a structured, 12-week exercise and nutrition
      program designed for cancer survivors and caregivers to complete concurrently.
      Interviews were conducted until data saturation was reached. RESULTS: Inductive
      content analysis from individual interviews indicated three separate, but
      interrelated, themes: (1) the program was a positive mechanism through which
      caregivers shared and supported the cancer journey concurrently with survivors,
      (2) the program led to perceived physical and psychological benefits for both
      caregivers and survivors, and (3) participants perceived that participation in
      the program led to feeling increased social support in their caregiving duties.
      CONCLUSIONS: Findings from this study suggest that participating in an exercise-
      and nutrition-based intervention is viewed positively by caregivers and that the
      outcomes are seen as beneficial to both caregivers and survivors. Interventions
      that address the health needs of both members of the caregiver-survivor dyad
      should continue to be encouraged by allied health professionals.

PMID- 22956193
TI  - Clinical changes in terminally ill cancer patients and death within 48 h: when
      should we refer patients to a separate room?
AB  - BACKGROUND: There is scant research concerning the prediction of imminent death,
      and current studies simply list events "that have already occurred" around 48 h
      of the death. We sought to determine what events herald the onset of dying
      process using the length of time from "any change" to death. METHODS: This is a
      prospective observational study with chart audit. Inclusion criteria were
      terminal cancer patients who passed away in a palliative care unit. The analysis
      was limited to 181 patients who had medical records for their final week.
      Commonly observed events in the terminally ill were determined and their
      significant changes were defined beforehand. We selected the statistically
      significant changes by multiple logistic regression analysis and evaluated their
      predictive values for "death within 48 h." RESULTS: The median age was 67 years
      and there were 103 male patients. After adjusting for age, sex, primary cancer
      site, metastatic site, and cancer treatment, multiple logistic regression
      analyses for association between the events and "death within 48 h" revealed some
      significant changes: confused mental state, decreased blood pressure, increased
      pulse pressure, low oxygen saturation, death rattle, and decreased conscious
      level. The events that had higher predictability for death within 48 h were
      decreased blood pressure and low oxygen saturation, and the positive and negative
      predictive values of their combination were 95.0 and 81.4%, respectively.
      CONCLUSION: The most reliable events to predict impending death were decreased
      blood pressure and low oxygen saturation.

PMID- 22956194
TI  - Medical, surgical and interventional management of hypertrophic cardiomyopathy
      with obstruction.
AB  - OPINION STATEMENT: Patients with hypertrophic cardiomyopathy (HCM) are classified
      as having hypertrophic obstructive cardiomyopathy (HOCM) if a left ventricular
      outflow tract (LVOT) gradient is present at rest or during provocation, as with
      Valsalva maneuver or exercise. Management of HCM in general and HOCM in
      particular encompasses (1) activity restriction with avoidance of volume
      depletion, (2) prevention of sudden cardiac death, (3) control of symptoms, and
      (4) screening of relatives. Those patients at high risk of sudden cardiac death
      (SCD) should be offered an implantable cardioverter-defibrillator (ICD).
      Pharmacologic treatment of symptoms in patients with HOCM consists of negative
      inotropic drugs, namely beta blockers, and disopyramide; a nondihydropyridine
      calcium channel blocker (CCB), usually verapamil, may be used in patients with
      noncardiac side-effects of beta blockers. Patients who have a dual-chamber
      pacemaker (PM) or ICD should undergo a trial of pacing with short
      atrioventricular (AV) delay. For patients with intolerable symptoms despite
      optimal conservative therapy, septal reduction therapy (SRT) should be considered
      and should be performed by experienced operators in institutions with
      multidisciplinary HCM programs. Younger patients with extreme hypertrophy are
      usually offered septal myectomy, while older patients, and those with important
      comorbidities are usually directed to alcohol septal ablation (ASA). For patients
      for whom either therapy is appropriate, there should be a balanced discussion
      with the patients of the benefits and risks of the 2 procedures.

PMID- 22956196
TI  - Bridging the gap between a TB drug and its target.
AB  - A promising new TB drug cocrystallized with its mycobacterial target provides a
      platform for structure-based design that will improve TB drug development (Neres
      et al.).

PMID- 22956195
TI  - Ferrous ammonium phosphate (FeNH4PO4) as a new food fortificant: iron
      bioavailability compared to ferrous sulfate and ferric pyrophosphate from an
      instant milk drink.
AB  - PURPOSE: The main purpose of this study was to establish bioavailability data in
      humans for the new (Fe) fortification compound ferrous ammonium phosphate (FAP),
      which was specially developed for fortification of difficult-to-fortify foods
      where soluble Fe compounds cannot be used due to their negative impact on product
      stability. METHODS: A double-blind, randomized clinical trial with cross-over
      design was conducted to obtain bioavailability data for FAP in humans. In this
      trial, Fe absorption from FAP-fortified full-cream milk powder was compared to
      that from ferric pyrophosphate (FPP) and ferrous sulfate. Fe absorption was
      determined in 38 young women using the erythrocyte incorporation dual stable
      isotope technique (57Fe, 58Fe). RESULTS: Geometric mean Fe absorption from
      ferrous sulfate, FAP and FPP was 10.4, 7.4 and 3.3 %, respectively. Fe from FAP
      was significantly better absorbed from milk than Fe from FPP (p < 0.0001). Fe
      absorption from FAP was significantly lower than Fe absorption from ferrous
      sulfate, which was used as water-soluble reference compound (p = 0.0002).
      Absorption ratios of FAP and FPP relative to ferrous sulfate as a measure of
      relative bioavailability were 0.71 and 0.32, respectively. CONCLUSIONS: The
      results of the present studies show that replacing FPP with FAP in full-cream
      milk could significantly improve iron bioavailability.

PMID- 22956197
TI  - The nexus of Abeta, aging, and sleep.
AB  - Roh et al. report a positive feedback loop between sleep-wake irregularities and
      aggregation of beta-amyloid peptide, suggesting that sleep alterations could be
      an early event in Alzheimer's disease.

PMID- 22956198
TI  - Regulatory science innovation: a rate-limiting step in translation.

PMID- 22956199
TI  - Structural basis for benzothiazinone-mediated killing of Mycobacterium
      tuberculosis.
AB  - The benzothiazinone BTZ043 is a tuberculosis drug candidate with nanomolar whole
      cell activity. BTZ043 targets the DprE1 catalytic component of the essential
      enzyme decaprenylphosphoryl-beta-D-ribofuranose-2'-epimerase, thus blocking
      biosynthesis of arabinans, vital components of mycobacterial cell walls. Crystal
      structures of DprE1, in its native form and in a complex with BTZ043, reveal
      formation of a semimercaptal adduct between the drug and an active-site cysteine,
      as well as contacts to a neighboring catalytic lysine residue. Kinetic studies
      confirm that BTZ043 is a mechanism-based, covalent inhibitor. This explains the
      exquisite potency of BTZ043, which, when fluorescently labeled, localizes DprE1
      at the poles of growing bacteria. Menaquinone can reoxidize the flavin adenine
      dinucleotide cofactor in DprE1 and may be the natural electron acceptor for this
      reaction in the mycobacterium. Our structural and kinetic analysis provides both
      insight into a critical epimerization reaction and a platform for structure-based
      design of improved inhibitors.

PMID- 22956200
TI  - Disruption of the sleep-wake cycle and diurnal fluctuation of beta-amyloid in
      mice with Alzheimer's disease pathology.
AB  - Aggregation of beta-amyloid (Abeta) in the brain begins to occur years before the
      clinical onset of Alzheimer's disease (AD). Before Abeta aggregation,
      concentrations of extracellular soluble Abeta in the interstitial fluid (ISF)
      space of the brain, which are regulated by neuronal activity and the sleep-wake
      cycle, correlate with the amount of Abeta deposition in the brain seen later. The
      amount and quality of sleep decline with normal aging and to a greater extent in
      AD patients. How sleep quality as well as the diurnal fluctuation in Abeta change
      with age and Abeta aggregation is not well understood. We report a normal sleep
      wake cycle and diurnal fluctuation in ISF Abeta in the brain of the
      APPswe/PS1deltaE9 mouse model of AD before Abeta plaque formation. After plaque
      formation, the sleep-wake cycle markedly deteriorated and diurnal fluctuation of
      ISF Abeta dissipated. As in mice, diurnal fluctuation of cerebrospinal fluid
      Abeta in young adult humans with presenilin mutations was also markedly
      attenuated after Abeta plaque formation. Virtual elimination of Abeta deposits in
      the mouse brain by active immunization with Abeta(42) normalized the sleep-wake
      cycle and the diurnal fluctuation of ISF Abeta. These data suggest that Abeta
      aggregation disrupts the sleep-wake cycle and diurnal fluctuation of Abeta. Sleep
      wake behavior and diurnal fluctuation of Abeta in the central nervous system may
      be functional and biochemical indicators, respectively, of Abeta-associated
      pathology.

PMID- 22956203
TI  - HIT: time to end behavioral health discrimination.
AB  - While the Health Information Technology for Economic and Clinical Health Act,
      enacted as part of the American Recovery and Reinvestment Act of 2009, provided
      $20.6 billion for incentive payments to support the adoption and meaningful use
      of health information technology (HIT), behavioral health organizations were not
      eligible to receive facility payments. The consequences of excluding behavioral
      health from HIT incentive payments are found in the results of the "HIT Adoption
      and Meaningful Use Readiness in Community Behavioral Health" survey. The survey
      found that only 2% of community behavioral health organizations are able to meet
      federal meaningful use (MU) requirements-compare this to the 27% of Federally
      Qualified Health Centers and 20% of hospitals that already meet some level of MU
      requirements. Behavioral health organizations, serving more than eight million
      adults, children, and families with mental illnesses and addiction disorders, are
      ready and eager to adopt HIT to meet the goals of better healthcare, better
      health, and lower costs. But reaching these goals may prove impossible unless
      behavioral health achieves "parity" within healthcare and receives resources for
      the adoption of HIT.

PMID- 22956201
TI  - An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in
      macaques.
AB  - Microbicides may prevent HIV and sexually transmitted infections (STIs) in women;
      however, determining the optimal means of delivery of active pharmaceutical
      ingredients remains a major challenge. We previously demonstrated that a vaginal
      gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150
      partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase)
      infection, and the addition of zinc acetate rendered the gel significantly
      protective. We test the activity of MIV-150 without the addition of zinc acetate
      when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal
      rings (IVRs). MIV-150 was successfully delivered, because it was detected in
      vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies.
      Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our
      results demonstrate that MIV-150-containing IVRs have the potential to prevent
      HIV infection and highlight the possible use of IVRs for delivering drugs that
      block HIV and other STIs.

PMID- 22956204
TI  - Randomized clinical trial of ropivacaine wound infusion following laparoscopic
      colorectal surgery.
AB  - BACKGROUND: Wound infusions with local anaesthesia have been used with varying
      success following laparotomy for colonic resections. This trial sought to
      determine the efficacy of ropivacaine wound infusion following laparoscopic
      colonic surgery. METHODS: Forty-eight consecutive patients undergoing elective
      laparoscopic colorectal resection were randomized to receive either a local
      anaesthetic wound infusion (ropivacaine 0.5%) or normal saline for a period of 72
      h. The primary endpoint was postoperative pain as assessed by analgesic
      consumption, while secondary endpoints assessed were visual analogue pain scores,
      respiratory function, gastrointestinal function, length of stay and postoperative
      complications. RESULTS: There was no difference in mean postoperative analgesic
      consumption between the two groups over 72 h (143 mEq morphine control vs 94 mEq
      intervention; p = 0.108). Likewise, there was no difference in daily
      postoperative analgesic consumption or visual analogue pain scores between the
      two groups. Patients in the ropivacaine group experienced less reduction in their
      postoperative forced expiratory volume at 1 s on day 1 (mean difference FEV1 0.4
      l; p = 0.015). There was no difference between the two groups with respect to
      return of gut function and postoperative complications. CONCLUSIONS: In this
      study, local anaesthetic wound infusion with ropivacaine following elective
      laparoscopic colorectal surgery improves early respiratory function, but does not
      appear to provide an improvement in postoperative analgesia or other clinically
      relevant postoperative outcomes.

PMID- 22956206
TI  - Comment on Meinero and Mori: Video-assisted anal fistula treatment (VAAFT): a
      novel sphincter-saving procedure to repair complex anal fistulas.

PMID- 22956208
TI  - The role of hemorrhoidectomy in rectocele complicated by grade 3-4 hemorrhoids.

PMID- 22956207
TI  - The challenge of pouch-vaginal fistulas: a systematic review.
AB  - Pouch-vaginal fistulae affect 6% of women after ileal pouch-anal anastomosis.
      Such fistulae significantly impact on the patient's quality of life and present a
      technical challenge to the surgeon. Although several operative approaches have
      been described, results from a number of case series are variable and associated
      with significant rates of failure. As a result, there remains a lack of consensus
      in the literature with regard to the management of this troublesome problem. The
      purpose of this article is to review the results of surgical intervention and to
      provide a clinical algorithm that gives a structured approach to the management
      of pouch-vaginal fistulae.

PMID- 22956209
TI  - Sexual function and quality of life after surgical treatment for anal fistulas in
      Crohn's disease.
AB  - BACKGROUND: The aim of this study was to assess sexual function and quality of
      life (QoL) in patients after surgery for perianal Crohn's disease. METHODS:
      Eighty-eight consecutive patients with perianal Crohn's disease, operated on at
      the Medical University of Vienna, completed a self-administered questionnaire
      including the International Index of Erectile Function (IIEF), Female Sexual
      Function Index (FSFI), Short Form-12 Health Survey (SF-12), and the Inflammatory
      Bowel Disease Questionnaire (IBDQ). Patients with a current stoma were excluded
      from further analysis. The median follow-up time was 104 months (range 3-186
      months). Healthy subjects served as controls for each case and were matched by
      age (+/-6 years) and gender. Forty-seven (68 %) female and 22 male patients with
      a median age of 46.5 years (range 18-64 years) were analyzed. Eleven (16 %)
      patients had simple and 58 (84 %) complex anal fistulas. RESULTS: The median SF
      12 physical health score of the patients was significantly lower (47.9 (range
      25.5-57.2)) than that of the controls (54.3 (range 34.6-61.8); p = 0.03). Not
      surprisingly, the median total sore of the IBDQ of the controls was significantly
      better than that of the patients (controls: 188.5 (range 125-206.5), patients:
      157 (range 60-199.5); p < 0.0001). Analysis with the multiple logistic regression
      test showed that type of operation, >1 perianal fistula opening, and active
      Crohn's disease were independent risk factors for a worse IBDQ (p = 0.03, p =
      0.015 and p < 0.0001). Interestingly, the median FSFI and IIEF score were not
      found to be significant different in any domain. CONCLUSIONS: QoL but not sexual
      function is significantly influenced by surgery for perianal Crohn's disease.

PMID- 22956210
TI  - Prescribing of zoledronic acid in a tertiary outpatient hospital setting.
AB  - BACKGROUND: Zoledronic acid (ZA) is an intravenous bisphosphonate approved for
      the prevention and treatment of cancer skeletal-related events. OBJECTIVE: Our
      aim was to analyze the prescription patterns of ZA in the cancer outpatient
      clinic. METHOD: We performed a retrospective chart review of all patients who
      received at least 1 dose of ZA from January 2009 until December 2010 in our
      institution. The patients' follow-up period was defined from the administration
      of the first dose until February 2011. RESULTS: The sample comprised 345
      patients: 31.9 % had breast cancer, 14.5 % prostate cancer, 29.0 % multiple
      myeloma, and 24.6 % other solid tumors. A total of 4,546 doses were administered;
      2,749 (60.5 %) without intravenous chemotherapy. 71.1 % of patients with breast
      cancer, 86 % with prostate cancer, 60 % with multiple myeloma and 44.6 % with
      other solid tumors, received ZA without intravenous chemotherapy throughout
      bisphosphonate treatment. Doses were adjusted in one-third of cases.
      Administration every 4-weeks was the most frequent schedule. Median duration of
      treatment varied between 15.0 months for breast cancer and 4.2 months for other
      solid tumors. CONCLUSION: Most of ZA prescriptions in cancer outpatients followed
      the labeled indications. The percentage of ZA doses administered without
      intravenous chemotherapy was 60.5 %.

PMID- 22956212
TI  - Flourish or flush: effects of simulated extreme rainfall events on Sphagnum
      dwelling testate amoebae in a subarctic bog (Abisko, Sweden).
AB  - Extreme precipitation events are recognised as important drivers of ecosystem
      responses to climate change and can considerably affect high-latitude
      ombrotrophic bogs. Therefore, understanding the relationships between increased
      rainfall and the biotic components of these ecosystems is necessary for an
      estimation of climate change impacts. We studied overall effects of increased
      magnitude, intensity and frequency of rainfall on assemblages of Sphagnum
      dwelling testate amoebae in a field climate manipulation experiment located in a
      relatively dry subarctic bog (Abisko, Sweden). The effects of the treatment were
      estimated using abundance, species diversity and structure of living and empty
      shell assemblages of testate amoebae in living and decaying layers of Sphagnum.
      Our results show that increased rainfall reduced the mean abundance and species
      richness of living testate amoebae. Besides, the treatment affected species
      structure of both living and empty shell assemblages, reducing proportions of
      hydrophilous species. The effects are counterintuitive as increased precipitation
      related substrate moisture was expected to have opposite effects on testate
      amoeba assemblages in relatively dry biotopes. Therefore, we conclude that other
      rainfall-related factors such as increased infiltration rates and frequency of
      environmental disturbances can also affect testate amoeba assemblages in Sphagnum
      and that hydrophilous species are particularly sensitive to variation in these
      environmental variables.

PMID- 22956211
TI  - Morphological and genetic characterization of endophytic bacteria isolated from
      roots of different maize genotypes.
AB  - Maize is one of the most important crops worldwide, and in Brazil, the state of
      Parana stands as its largest producer. The crop demands high inputs of N
      fertilizers, therefore all strategies aiming to optimize the grain production
      with lower inputs are very relevant. Endophytic bacteria have a high potential to
      increment maize grain yield by means of input via biological nitrogen fixation
      and/or plant growth promotion, in this last case increasing the absorption of
      water and nutrients by the plants. In this study, we established a collection of
      217 endophytic bacteria, isolated from roots of four lineages and three hybrid
      genotypes of maize, and isolated in four different N-free culture media.
      Biochemical-comprising growth in different carbon sources, intrinsic tolerance to
      antibiotics, and biochemical tests for catalase, nitrate reductase, urease, and
      growth in N-free media in vitro-and genetic characterization by BOX-PCR revealed
      great variability among the isolates. Both commercial hybrids and homozygous
      lineages were broadly colonized by endophytes, and sequencing of the 16S rRNA
      gene revealed the presence of bacteria belonging to the genera Pantoea, Bacillus,
      Burkholderia, and Klebsiella. Qualitative differences in endophytic colonization
      were detected between lineages and hybrid genotypes.

PMID- 22956215
TI  - Community variation in adolescent alcohol use in Australia and the Netherlands.
AB  - To investigate the cross-national relevance of community health promotion, this
      paper compared community variation in alcohol use and risk and protective factors
      for adolescents in Australia (State of Victoria, 2009) and the Netherlands
      (2007/2008). Multi-level analyses examined community variation in heavy episodic
      (binge) alcohol use [>=5 drinks in a session >=once in the prior fortnight (>63
      ml of ethanol)] and associations with predictors. Representative community
      samples of adolescents (12-17 years) were recruited. The participants were 7812
      students from 36 Australian communities and 15 082 adolescents from 124 Dutch
      communities. Predictors included adolescent reports of family, school, peer and
      neighbourhood environments and community predictors (rural, disadvantage). The
      overall prevalence of alcohol use prevalence was similar in both nations.
      Australia had higher use at younger ages and no difference between genders. In
      the Netherlands older adolescents and males used alcohol at significantly higher
      rates. Although individual predictors were mostly similar, binge drinking was
      more strongly associated with poor family management, friends' use of drugs and
      community disorganization in Australia. Significant community variation in
      adolescent heavy alcohol use was observed in both countries, but was higher in
      the Netherlands [inter class correlation 6.1%, (95% CI: 4.5-8.3%)] than Australia
      (ICC 2.4%, 1.3-4.5%). Youth from rural areas drank at a higher level, especially
      in the Netherlands. Targeting community level adolescent alcohol use appears
      feasible in both countries. Although behavioural patterns and risk and protective
      influences are similar in the Netherlands and Australia, important differences
      should be taken into account in tailoring community interventions. 

PMID- 22956216
TI  - Health promoting hospitals in Lithuania: health professional support for
      standards.
AB  - The standards for health promotion (HP) addressing five domains such as (1)
      management policy, (2) patient assessment, (3) patient information and
      intervention, (4) promoting a healthy workplace and (5) improving continuity and
      cooperation have been elaborated and applied within the International Networks of
      Health Promoting Hospitals (HPH). The awareness of HP activities by health
      professionals and their opinions as to the applicability of the five HP standards
      in three randomly selected hospitals of the Lithuanian HPH network was assessed.
      A questionnaire survey of physicians and nurses (including chiefs of the selected
      departments as managerial staff) working in three different-sized hospitals was
      carried out. The overall response rate constituted 74.7%, with 280 physicians and
      739 nurses completing the survey. One in four respondents stated that the first,
      second and fifth standards could be implemented into daily practice whereas one
      in three respondents held the same belief in respect to the third and fourth
      standards. Health professionals from the small hospital possessed better
      knowledge and demonstrated a more positive opinion with respect to the
      applicability of all five standards compared with the larger hospitals. No
      difference was observed between the opinions of physicians and nurses concerning
      the applicability of the first and second HP standards, yet a significantly
      larger number of nurses, compared with physicians, expressed a positive attitude
      towards the implementation of the remaining three standards. More physicians and
      nurses with managerial roles, compared with those not involved in the management
      of hospitals, reported that all five standards could be integrated into daily
      practice. 

PMID- 22956217
TI  - [Prediabetes: high risk factor for diabetes mellitus type 2?  - Successful
      prevention with early interventions for lifestyle modification].

PMID- 22956218
TI  - [Visceral medicine: a successful collaboration].

PMID- 22956219
TI  - [Efficacy of freeze-dried Lactobacilli in functional diarrhoe: a pilot study].
AB  - BACKGROUND AND OBJECTIVE: The pathogenic role of the intestinal milieu for
      symptoms in functional bowel disorders such as functional diarrhea (FD) or
      associated pain and bloating in the irritable bowel syndrome (IBS) is the
      rationale for probiotic treatment approaches. It was the aim of this pilot study
      to test the effects of a lyophilisate from devitalized lactobacilli and their
      culture medium in patients with chronic FD. METHODS: Following a one-week basal
      period, 22 patients mit FD (12 with IBS) were treated with Lacteol (2
      capsules/day) for 4 weeks. Stool frequency, consistency (assessed by BSFS), urge,
      pain and bloating were recorded daily using a standardized symptom diary, and
      global relief was recorded weekly. RESULTS: Daily stool frequency and number of
      days with urge were significantly decreased starting in week 1 (-0.6 +/- 0.2/day;
      p = 0.005; and -1.3 +/- 0.3 days, respectively; p = 0.001). This effect persisted
      throughout week 4 (-0.6 +/- 0.2/day; p< 0.02; and -1.4 +/- 0.5 days,
      respectively; p = 0.025). After 4 weeks, 50% of patients reported satisfactory
      symptom relief, including improvement in maximal stool consistency (BSFS: -0.3 +/
      0.2; p = 0.04), and 43% of patients recorded a decrease in stool frequency of >=
      25%. CONCLUSION: These findings suggest a clinically relevant efficacy of Lacteol
      in a subgroup of patients with FD, particularly with regard to stool frequency,
      urge and stool consistency. As the study design does not allow to exclude that a
      placebo component might have contributed to these effects, the results should be
      corroborated in an larger, placebo-controlled trial.

PMID- 22956220
TI  - [PPI-sensitive diarrhea - unusual case of an adolescent with sporadic
      gastrinoma].
AB  - HISTORY AND CLINICAL FINDINGS: A 14-year-old boy was admitted to hospital because
      of chronic episodic diarrhea lasting for 4 years. Previous investigations in the
      past had not revealed the cause of the symptoms. INVESTIGATIONS: The 13C
      triglyceride breathing test showed a diminished intestinal lipolysis. Endoscopic
      examination demonstrated small gastroduodenic ulcers. During therapy with proton
      pump inhibitors the diarrhea stopped. DIAGNOSIS, TREATMENT AND COURSE: The
      combination of gastroduodenic ulcers and improvement of diarrhea with PPI-therapy
      were suggestive of Zollinger-Ellison syndrome. Endosonography and MR-scan showed
      an extrapancreatic mass with marked activity during somatostatin receptor
      scintigraphy. The primary tumor was excised, a liver metastasis was treated with
      radiofrequency ablation. The histological examination confirmed the diagnosis of
      a gastrinoma. CONCLUSION: In patients with chronic diarrhea, especially if the
      symptoms are PPI-sensitive, a gastrinoma should be considered.

PMID- 22956221
TI  - [51-year-old patient with unsuspected X-ray finding during ERCP].

PMID- 22956222
TI  - [Immunosuppression in inflammatory bowel disease:  When, how and how long?].
AB  - Immunosuppressive treatment is an important tool in the therapy of patients with
      inflammatory bowel disease. Treatment goal is a long lasting remission.
      Candidates for immunosuppressive treatment are patients with steroid-refractory
      active disease, steroid-dependency, chronic active disease or frequent relapses.
      Conventional immunosuppressives (azathioprine/6-mercaptopurine, methotrexate, the
      calcineurin inhibitors cyclosporine A and tacrolimus), and anti-TNF antibodies
      (infliximab, adalimumab) are available. Current guidelines set the frame for the
      rational use of these drugs.

PMID- 22956223
TI  - [Colorectal cancer: role of surgery in hepatic metastases - the internist's point
      of view].

PMID- 22956224
TI  - [Colorectal cancer: role of surgery in hepatic metastases - the surgery's point
      of view].

PMID- 22956225
TI  - [Diverticular diseases of the colon].

PMID- 22956226
TI  - [New tests for the prevention of colorectal cancer].

PMID- 22956227
TI  - [Do we need gastric acid?].

PMID- 22956228
TI  - [Gastric cancer: (neo-)adjuvant treatment].

PMID- 22956229
TI  - Sexual partnership types as determinant of HIV risk in South African MSM: an
      event-level cluster analysis.
AB  - While individual determinants of HIV risk among MSM have been widely studied,
      there is limited understanding of how relational characteristics determine sexual
      risk. Based on data collected among 300 South African men who have sex with men
      (MSM) and using cluster analysis, this study developed a typology of four
      partnership types: the "Race-Economic Similar," "Age-Race-Economic Discordant,"
      "Non-regular Neighbourhood," and "Familiar" partnership types. Support for the
      meaningfulness of these types was found through associations of these partnership
      types with participant characteristics and characteristics of the last anal sex
      event. Furthermore, in a multivariate analysis, only partnership type
      independently predicted whether the last anal sex event was unprotected. Findings
      of the study illustrate the importance of taking into account the relational
      context in understanding unprotected sexual practices and present ways to target
      intervention efforts as well as identify relationship specific determinants of
      unprotected sex.

PMID- 22956230
TI  - Chromomeres revisited.
AB  - The history of studies on the chromomeres of lampbrush chromosomes is outlined
      and evidence for the nature and function of these structures is collected and
      summarised. Chromomeres and their associated loops on lampbrush chromosomes are
      not genetic units although in some special cases, they consist of specific
      families of repeated DNA sequences. The emergence of a chromomeric organisation
      coincides with the onset and intensification of transcription on lampbrush loops.
      Modern molecular studies have provided evidence that the chromatin of lampbrush
      chromomeres differs in several important respects from that of condensed
      metaphase chromosomes. It is in a highly dynamic state that facilitates localised
      transcription whilst keeping the chromosome safe from structural changes that
      might impede its orderly progression up to and through meiotic metaphase 1.
      Lampbrush chromosomes (LBCs) are a physically induced phenomenon, facilitated by
      the selective absence of molecular factors that would interfere with their main
      transcriptional role. LBC morphology is highly dynamic and driven by
      transcriptive activity.

PMID- 22956231
TI  - Duplication of the left vertebral artery in a patient with dissection of the
      right internal carotid artery and Ehlers-Danlos syndrome: case report and review
      of the literature.
AB  - Duplication of the left vertebral artery was observed in a 43-year-old Caucasian
      male with dissection of the right internal carotid artery during multidetector 64
      row computer tomography and Doppler ultrasonography B-flow mode. Both duplicated
      segments arose from the left subclavian artery and united at levels C5-C6 to form
      a single vessel. The presented case describes precisely the origin and diameter
      of both vertebral arteries. Additionally, after all procedures associated with
      diagnosis and treatment of the patient, Ehlers-Danlos syndrome type IV was
      diagnosed. The lumen of the duplicated vertebral artery was smaller than normal;
      it can be concluded that this variant has clinical implications and should be
      taken into consideration when vertebral arteries need catheterization.

PMID- 22956232
TI  - alpha-Synuclein oligomers: an amyloid pore? Insights into mechanisms of alpha
      synuclein oligomer-lipid interactions.
AB  - In many human diseases, oligomeric species of amyloid proteins may play a pivotal
      role in cytotoxicity. Many lines of evidence indicate that permeabilization of
      cellular membranes by amyloid oligomers may be the key factor in disrupting
      cellular homeostasis. However, the exact mechanisms by which the membrane
      integrity is impaired remain elusive. One prevailing hypothesis, the so-called
      amyloid pore hypothesis, assumes that annular oligomeric species embed into lipid
      bilayers forming transbilayer protein channels. Alternatively, an increased
      membrane permeability could be caused by thinning of the hydrophobic core of the
      lipid bilayer due to the incorporation of the oligomers between the tightly
      packed lipids, which would facilitate the transport of small molecules across the
      membrane. In this review, we briefly recapitulate our findings on the structure
      of alpha-synuclein oligomers and the factors influencing their interaction with
      lipid bilayers. Our results, combined with work from other groups, suggest that
      alpha-synuclein oligomers do not necessarily form pore-like structures. The
      emerging consensus is that local structural rearrangements of the protein lead to
      insertion of specific regions into the hydrophobic core of the lipid bilayer,
      thereby disrupting the lipid packing.

PMID- 22956233
TI  - Do patients lose weight after joint arthroplasty surgery? A systematic review.
AB  - BACKGROUND: The ability of patients with a total joint arthroplasty (TJA) to lose
      weight after surgery has been investigated in a few studies with inconsistent
      results. QUESTIONS/PURPOSES: We asked: (1) What is the quality of evidence of
      current published literature on postoperative weight trends for patients who have
      had a TJA? (2) Do patients lose any weight after TJA? (3) Do patients lose a
      clinically meaningful amount of weight after TJA? METHODS: We conducted a
      systematic review of PubMed and the Cochrane Library. Studies were summarized
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      analyses Statement. Studies were reviewed for quality of evidence and limitations
      according to the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) criteria. Twelve studies were identified, one case-cohort
      study and 11 case series. Most studies were from single-surgeon or single
      hospital series. Five studies included THAs and TKAs, four only THAs, and three
      only TKAs. We determined study type, level of evidence, inclusion criteria,
      procedures, proportion of patients who changed weight, body composition
      assessment, time of composition assessment, statistical analysis performed, and
      subgroup analysis conducted. RESULTS: Owing to the observational nature of the
      studies and the serious limitations identified, all were considered very low
      quality according to GRADE criteria. Studies reported 14% to 49% of patients had
      some weight loss at least 1 year postoperatively. CONCLUSIONS: We found no
      conclusive evidence that weight or body composition increases, decreases, or
      remains the same after TJA.

PMID- 22956234
TI  - CORR insights: do patients lose weight after joint arthroplasty surgery? A
      systematic review.
AB  - This CORR InsightsTM is a commentary on the article "Do Patients Lose Weight
      After Joint Arthroplasty Surgery? A Systematic Review" by Inacio and colleagues
      available at DOI 10.1007/s11999-012-2537-7 .

PMID- 22956235
TI  - What factors affect posterior dislocation distance in THA?
AB  - BACKGROUND: Dislocation remains common after total hip arthroplasty. Efforts have
      been made to identify and minimize risk factors. One such factor, jump distance,
      or the distance the femoral head must travel before dislocating, has been poorly
      characterized with respect to three-dimensional kinematics. QUESTIONS/PURPOSES:
      We therefore determined: (1) the three-dimensional stability of four different
      component designs; (2) whether the degree of abduction and anteversion affects
      the stability; (3) whether pelvic inclination angles affected stability; and (4)
      which combination of these three factors had the greatest stability. METHODS: We
      created a positionable three-dimensional model of a THA. Acetabular components
      were modeled in various abduction and anteversion angles and in two different
      pelvic inclinations which simulate standing and chair-rising activities. RESULTS:
      The posterior horizontal dislocation distance increased as inclination angle and
      femoral head size increased. The 48-mm resurfacing typically had lower jump
      distances and was at risk of posterior edge loading at 30 degrees  inclination.
      The highest jump distance for all positions and activities occurred with the dual
      mobility bearing. CONCLUSION: These findings suggest that monoblock cups require
      extremely accurate positioning for low dislocation risk and that pelvic
      orientation may increase dislocation risks. CLINICAL RELEVANCE: As a result of
      the dual-mobility designs having the greatest resistance to dislocation, these
      cups may be appropriate for patients who are at risk for dislocation in difficult
      primary situations and in revision hip arthroplasty procedures in which proper
      component orientation may be less likely to be achieved.

PMID- 22956236
TI  - Risk factors for dislocation after revision total hip arthroplasty.
AB  - BACKGROUND: Despite dislocation being the most frequent complication after
      revision THA, risk factors for its occurrence are not completely understood.
      QUESTIONS/PURPOSES: We therefore (1) determined the overall risk of dislocation
      after revision THA in a large series of revision THAs using contemporary revision
      techniques, (2) identified patient-related risk factors predicting dislocation,
      and (3) identified surgical variables predicting dislocation. METHODS: We
      performed 1211 revision THAs between June 2004 and October 2010 in 576 women and
      415 men who had a mean age of 64.7 years (range, 25-95 years) at time of surgery.
      Forty-six (4%) were lost to followup and 13 died (1%), leaving 1152 hips followed
      for a minimum of 90 days (mean, 2 years; range, 90 days to 7.1 years).
      Multivariate logistic regression was performed to identify risk factors for
      dislocation. The model was also tested on patients followed for a minimum 1 year
      to assess any difference in longer followup. RESULTS: One hundred thirteen
      patients dislocated over the followup period (9.8%). Factors that were different
      between patients who dislocated and those who remained stable included a history
      of at least one previous dislocation (odds ratio [OR] = 2.673), abductor
      deficiency (OR = 2.672), and Paprosky acetabulum class (OR = 1.522). Use of a
      constrained liner (OR = 0.503) and increased femoral head size (OR = 0.942) were
      protective against dislocation, while with longer followup a constrained liner
      was no longer significant. CONCLUSIONS: Dislocation remains a common problem
      after revision THA. Identifying these risk factors can assist in patient
      education and surgical planning. Recognition of these risk factors in both
      patient type and surgical strategy is important for the surgeon performing
      revision THA and for minimizing these risks. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 22956237
TI  - Wear-corrosion synergism in a CoCrMo hip bearing alloy is influenced by proteins.
AB  - BACKGROUND: Although numerous in vitro studies report on the tribological
      performance of and, separately, on the corrosion properties of cobalt-based
      alloys in metal-on-metal (MoM) bearings, the few studies that take into account
      the synergistic interaction of wear and corrosion (tribocorrosion) have used
      canonical tribo-test methods. We therefore developed synergistic study using a
      test method that more closely simulates hip bearing conditions.
      QUESTIONS/PURPOSES: (1) Is the total material loss during tribocorrosion larger
      than the sum of its components generated during isolated mechanical wear and
      isolated corrosion? (2) How is the tribocorrosive process affected by the
      presence of protein? METHODS: High carbon CoCrMo alloy discs (18) were subjected
      to corrosion and tribocorrosion tests under potentiostatic conditions in an
      apparatus simulating hip contact conditions. The input variables were the applied
      potential and the protein content of the electrolyte (NaCl solution versus bovine
      serum, 30 g/L protein). The output variables were mass loss resulting from wear
      in the absence of corrosion, mass loss resulting from corrosion in the absence of
      wear, and the total mass loss under tribocorrosion, from which the additional
      mass loss resulting from the combined action of wear and corrosion, or synergism,
      was determined in the presence and absence of protein. RESULTS: The degradation
      mechanisms were sensitive to the interaction of wear and corrosion. The
      synergistic component (64 MUg) in the presence of protein amounted to 34% of
      total material loss (187 MUg). The presence of protein led to a 23% decrease in
      the total mass loss and to a considerable reduction in the mean current (4 MUA to
      0.05 MUA) under tribocorrosion. CONCLUSIONS: Synergistic effects during
      tribocorrosion may account for a considerable portion of MoM degradation and are
      affected by proteins. CLINICAL RELEVANCE: The in vivo performance of some large
      diameter MoM joints is unsatisfactory. The synergistic component resulting from
      tribocorrosion may have been missed in conventional preclinical wear tests.

PMID- 22956238
TI  - Lymphadenectomy and histologic subtype affect overall survival of soft tissue
      sarcoma patients with nodal metastases.
AB  - BACKGROUND: Lymph node metastases in patients with soft tissue sarcomas are rare
      and these metastases are frequently associated with certain histologic subtypes.
      The survival is believed to be poor if lymph node metastases occur and the
      potential benefit of lymphadenectomy is unclear. QUESTIONS/PURPOSES: We
      determined whether lymph node metastases affect overall survival with regard to
      the status of lymphadenectomy, histologic subtypes, isolated or systemic
      metastasis, and the timing of presentation of lymph node metastases. METHODS: We
      retrospectively reviewed all 871 patients diagnosed with soft tissue sarcomas
      between 1983 and 2008 to determine whether they had lymph node metastases at
      diagnosis or subsequently and whether they had lymphadenectomy for treatment.
      Overall survival was assessed and the effect of prognostic variables was examined
      by a log rank test. RESULTS: Forty-nine of the 871 patients (6%) had lymph node
      metastases. The estimated 5-year survival rate for the group of 49 patients with
      lymph node metastases was 27%. Those who had lymphadenectomy had better survival
      at 1.5 years although there was no difference between those who did not undergo
      lymphadenectomy at 5 years. Patients with nonrhabdomyosarcoma had better overall
      survival than patients with rhabdomyosarcoma. Timing of development of lymph node
      involvement and whether lymph node metastases were an isolated site did not
      affect the overall survival. CONCLUSIONS: Overall survival of patients with lymph
      node metastases was related to histologic subtypes and patients with
      nonrhabdomyosarcoma had better survival than those with rhabdomyosarcoma.
      Resection of the metastatic lymph node did not improve long-term survival of
      patients with soft tissue sarcomas. LEVEL OF EVIDENCE: Level II, prognostic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 22956239
TI  - Patient-specific total knee arthroplasty required frequent surgeon-directed
      changes.
AB  - BACKGROUND: Patient-specific instrumentation potentially improves surgical
      precision and decreases operative time in total knee arthroplasty (TKA) but there
      is little supporting data to confirm this presumption. QUESTIONS/PURPOSES: We
      asked whether patient-specific instrumentation would require infrequent
      intraoperative changes to replicate a single surgeon's preferences during TKA and
      whether patient-specific instrumentation guides would fit securely. METHODS: We
      prospectively evaluated the plan and surgery in 60 patients treated with 66 TKAs
      performed with patient-specific instrumentation and recorded any changes. A
      subset of six postoperative radiographic changes to the femoral and tibial
      components (implant size, coronal and sagittal alignment) was analyzed to
      determine if surgeon intervention was beneficial. Each guide was evaluated to
      determine fit. We compared patient demographics and implant sizing in the patient
      specific instrumentation group with a control group in which traditional
      instrumentation was used. RESULTS: We recorded 161 intraoperative changes in 66
      knee arthroplasties (2.4 changes/knee) performed with patient-specific
      instrumentation. The predetermined implant size was changed intraoperatively in
      77% of femurs and 53% of tibias. We identified a subset of 95 intraoperative
      changes that could be radiographically evaluated to determine if our changes were
      an improvement or detriment to reaching goal alignment. Eighty-two of the 95
      changes (86%) made by the surgeon were an improvement to the recommended
      alignment or size of patient-specific instrumentation. The guide did not fit
      securely on eight femurs (12%) and three tibias (5%). Tourniquet time and blood
      loss were not improved with patient-specific instrumentation. CONCLUSIONS: We
      caution surgeons against blind acceptance of patient-specific instrumentation
      technology without supportive data.

PMID- 22956241
TI  - Recurrence of IgG4-related disease following treatment with rituximab.
AB  - A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated
      lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy.
      She initially responded to the rituximab therapy, but later experienced two
      recurrences over a 3-year period. Biopsy specimens and a review of her previous
      histology revealed that she had had immunoglobulin G4-related disease at the
      initial presentation. Although IgG4-related disease seems to respond well to
      rituximab therapy, long-term follow up, including disease monitoring, is needed
      to evaluate disease remission. 

PMID- 22956240
TI  - Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients.
AB  - Translocator protein (18 kDa) (TSPO) is a marker of inflammation in the brain.
      Positron emission tomography (PET) scans with ligands for this receptor show
      increased expression of TSPO in many neuropathologic conditions. However,
      expression of TSPO in the periphery and its possible correlation to central
      nervous system (CNS) inflammation has been largely unstudied. In this paper
      PBR28, a recently synthesized ligand for TSPO that is shown to have 80-fold
      higher specific binding than its predecessor PK11195, is used to quantify
      peripheral TSPO. Data presented in this study show that monocytes account for the
      majority of TSPO measured in peripheral blood mononuclear cells (PBMC), and that
      TSPO expression is stable over time in healthy individuals. Previous studies show
      that areas of increased PBR28 binding in the brains of multiple sclerosis (MS)
      patients correlate with active demylinating lesions found during magnetic
      resonance imaging (MRI). To measure peripheral TSPO expression in an inflammatory
      disease of the CNS, PBR28 is used in an in vitro radioligand binding assay to
      measure the amount of TSPO in the PBMC of MS and healthy donor cohorts.
      Surprisingly, MS patients are found to have a significantly lower amount of
      peripheral TSPO than healthy donors. We suggest that TSPO protein expression is a
      potential peripheral biomarker of MS, more research is needed to determine if
      peripheral TSPO expression may also be altered in other neuroinflammatory
      conditions.

PMID- 22956242
TI  - Physico-chemical characteristics of TNFalpha blockers and their effectiveness in
      the treatment of rheumatoid arthritis: the theoretical and real worlds.

PMID- 22956244
TI  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals
      cholesterol overload in the cerebral cortex of Alzheimer disease patients.
AB  - Although cholesterol has been involved in the pathophysiology of Alzheimer
      disease (AD), its distribution in the cerebral cortex over the course of AD is
      unknown. We describe an original method to quantify cholesterol distribution
      using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was
      unevenly distributed along the cortical thickness, being more abundant close to
      the white matter, in both control and AD cases. However, the mean cholesterol
      signal was significantly higher in the lower half of the cortex in AD samples
      compared to controls. This increase, when converted into cortical layers, was
      statistically significant for layers III and IV and did not reach significance in
      layers V + VI, the variability being too high at the interface between grey and
      white matter. The density of neurofibrillary tangles and of senile plaques was
      not statistically linked to the abundance of cholesterol. Cholesterol overload
      thus appears a new and independent alteration of AD cerebral cortex. The
      structure in which cholesterol accumulates and the mechanism of this accumulation
      remain to be elucidated.

PMID- 22956243
TI  - Curative effect of Terminalia chebula extract on acetic acid-induced experimental
      colitis: role of antioxidants, free radicals and acute inflammatory marker.
AB  - The present study has evaluated the healing effects of extract of dried fruit
      pulp of Terminalia chebula (TCE) on acetic acid (AA)-induced colitis in rats. TCE
      (600 mg/kg) showed healing effects against AA-induced colonic damage score and
      weight when administered orally daily for 14 days. TCE was further studied for
      its effects on various physical (mucus/blood in stool and stool frequency, food
      and water intake and body weight changes), histology, antibacterial activity and
      free radicals (NO and LPO), antioxidants (SOD, CAT and GSH) and myeloperoxidase
      in colonic tissue. Intra-colonic AA administration increased colonic mucosal
      damage and inflammation, mucus/bloody diarrhoea, stool frequency, but decreased
      body weight which were reversed by TCE and sulfasalazine (SS, positive control)
      treatments. TCE showed antibacterial activity and both TCE and SS enhanced the
      antioxidants, but decreased free radicals and myeloperoxidase activities affected
      in acetic acid-induced colitis. TCE indicated the presence of active principles
      with proven antioxidants, anti-inflammatory, immunomodulatory, and free radical
      scavenging and healing properties. Thus, TCE seemed to be safe and effective in
      healing experimental colitis.

PMID- 22956246
TI  - Light and vision in the deep-sea benthos: I. Bioluminescence at 500-1000 m depth
      in the Bahamian islands.
AB  - Bioluminescence is common and well studied in mesopelagic species. However, the
      extent of bioluminescence in benthic sites of similar depths is far less studied,
      although the relatively large eyes of benthic fish, crustaceans and cephalopods
      at bathyal depths suggest the presence of significant biogenic light. Using the
      Johnson-Sea-Link submersible, we collected numerous species of cnidarians,
      echinoderms, crustaceans, cephalopods and sponges, as well as one annelid from
      three sites in the northern Bahamas (500-1000 m depth). Using mechanical and
      chemical stimulation, we tested the collected species for light emission, and
      photographed and measured the spectra of the emitted light. In addition, in situ
      intensified video and still photos were taken of different benthic habitats.
      Surprisingly, bioluminescence in benthic animals at these sites was far less
      common than in mesopelagic animals from similar depths, with less than 20% of the
      collected species emitting light. Bioluminescent taxa comprised two species of
      anemone (Actinaria), a new genus and species of flabellate Parazoanthidae
      (formerly Gerardia sp.) (Zoanthidea), three sea pens (Pennatulacea), three bamboo
      corals (Alcyonacea), the chrysogorgiid coral Chrysogorgia desbonni (Alcyonacea),
      the caridean shrimp Parapandalus sp. and Heterocarpus ensifer (Decapoda), two
      holothuroids (Elasipodida and Aspidochirota) and the ophiuroid Ophiochiton
      ternispinus (Ophiurida). Except for the ophiuroid and the two shrimp, which
      emitted blue light (peak wavelengths 470 and 455 nm), all the species produced
      greener light than that measured in most mesopelagic taxa, with the emissions of
      the pennatulaceans being strongly shifted towards longer wavelengths. In situ
      observations suggested that bioluminescence associated with these sites was due
      primarily to light emitted by bioluminescent planktonic species as they struck
      filter feeders that extended into the water column.

PMID- 22956245
TI  - Mapping of wheat mitochondrial mRNA termini and comparison with breakpoints in
      DNA homology among plants.
AB  - Mitochondrial DNA rearrangements occur very frequently in flowering plants and
      when close to genes there must be concomitant acquisition of new regulatory cis
      elements. To explore whether there might be limits to such DNA shuffling, we have
      mapped the termini of mitochondrial mRNAs in wheat, a monocot, and compared them
      to the known positions for counterpart genes in the eudicot Arabidopsis. Nine
      genes share homologous 3' UTRs over their full-length and for six of them, the
      termini map very close to the site of wheat/Arabidopsis DNA rearrangements. Only
      one such case was seen for comparisons of 5' UTRs, and the 5' ends of mRNAs are
      typically more heterogeneous than 3' termini. Approximately half of the thirty
      one wheat mitochondrial transcriptional units are preceded by CRTA promoter-like
      motifs, and of the potential stem-loop or tRNA-like structures identified as
      candidate RNA processing/stability signals near the 5' or 3' ends, several are
      shared with Arabidopsis. Comparison of the mitochondrial gene flanking sequences
      from normal fertile wheat (Triticum aestivum) with those of Aegilops kotschyi
      which is the source of mitochondria present in K-type cytoplasmic male sterile
      wheat, revealed six cases where mRNAs are precluded from sharing full-length
      homologous UTRs because of genomic reorganization events, and the presence of
      short repeats located at the sites of discontinuity points to a reciprocal
      recombination-mediated mode of rearrangement.

PMID- 22956247
TI  - Light and vision in the deep-sea benthos: II. Vision in deep-sea crustaceans.
AB  - Using new collecting techniques with the Johnson-Sea-Link submersible, eight
      species of deep-sea benthic crustaceans were collected with intact visual
      systems. Their spectral sensitivities and temporal resolutions were determined
      shipboard using electroretinography. Useable spectral sensitivity data were
      obtained from seven species, and in the dark-adapted eyes, the spectral
      sensitivity peaks were in the blue region of the visible spectrum, ranging from
      470 to 497 nm. Under blue chromatic adaptation, a secondary sensitivity peak in
      the UV portion of the spectrum appeared for two species of anomuran crabs:
      Eumunida picta (lambda(max)363 nm) and Gastroptychus spinifer (lambda(max)383
      nm). Wavelength-specific differences in response waveforms under blue chromatic
      adaptation in these two species suggest that two populations of photoreceptor
      cells are present. Temporal resolution was determined in all eight species using
      the maximum critical flicker frequency (CFF(max)). The CFF(max) for the isopod
      Booralana tricarinata of 4 Hz proved to be the lowest ever measured using this
      technique, and suggests that this species is not able to track even slow-moving
      prey. Both the putative dual visual pigment system in the crabs and the extremely
      slow eye of the isopod may be adaptations for seeing bioluminescence in the
      benthic environment.

PMID- 22956248
TI  - Oblique color vision in an open-habitat bird: spectral sensitivity, photoreceptor
      distribution and behavioral implications.
AB  - Color vision is not uniform across the retina because of differences in
      photoreceptor density and distribution. Retinal areas with a high density of cone
      photoreceptors may overlap with those with a high density of ganglion cells,
      increasing hue discrimination. However, there are some exceptions to this cell
      distribution pattern, particularly in species with horizontal visual streaks
      (bands of high ganglion cell density across the retina) that live in open
      habitats. We studied the spectral sensitivity and distribution of cone
      photoreceptors involved in chromatic and achromatic vision in the Canada goose
      (Branta canadiensis), which possesses an oblique rather than horizontal visual
      streak at the ganglion cell layer. Using microspectrophotometry, we found that
      the Canada goose has a violet-sensitive visual system with four visual pigments
      with absorbance peaks at 409, 458, 509 and 580 nm. The density of most cones
      involved in chromatic and achromatic vision peaked along a band across the retina
      that matched the oblique orientation of the visual streak. With the information
      on visual sensitivity, we calculated chromatic and achromatic contrasts of
      different goose plumage regions. The regions with the highest visual saliency
      (cheek, crown, neck and upper tail coverts) were the ones involved in visual
      displays to maintain flock cohesion. The Canada goose oblique visual streak is
      the retinal center for chromatic and achromatic vision, allowing individuals to
      sample the sky and the ground simultaneously or the horizon depending on head
      position. Overall, our results show that the Canada goose visual system has
      features that make it rather different from that of other vertebrates living in
      open habitats.

PMID- 22956249
TI  - Evidence that glucose is the major transferred metabolite in dinoflagellate
      cnidarian symbiosis.
AB  - Reef-building corals and many other cnidarians are symbiotic with dinoflagellates
      of the genus Symbiodinium. It has long been known that the endosymbiotic algae
      transfer much of their photosynthetically fixed carbon to the host and that this
      can provide much of the host's total energy. However, it has remained unclear
      which metabolite(s) are directly translocated from the algae into the host
      tissue. We reexamined this question in the small sea anemone Aiptasia using
      labeling of intact animals in the light with (13)C-bicarbonate, rapid
      homogenization and separation of animal and algal fractions, and analysis of
      metabolite labeling by gas chromatography-mass spectrometry. We found labeled
      glucose in the animal fraction within 2 min of exposure to (13)C-bicarbonate,
      whereas no significant labeling of other compounds was observed within the first
      10 min. Although considerable previous evidence has suggested that glycerol might
      be a major translocated metabolite, we saw no significant labeling of glycerol
      within the first hour, and incubation of intact animals with (13)C-labeled
      glycerol did not result in a rapid production of (13)C-glucose. In contrast, when
      Symbiodinium cells freshly isolated from host tissue were exposed to light and
      (13)C-bicarbonate in the presence of host homogenate, labeled glycerol, but not
      glucose, was detected in the medium. We also observed early production of labeled
      glucose, but not glycerol, in three coral species. Taken together, the results
      suggest that glucose is the major translocated metabolite in dinoflagellate
      cnidarian symbiosis and that the release of glycerol from isolated algae may be
      part of a stress response.

PMID- 22956250
TI  - Latino/a depression and smoking: an analysis through the lenses of culture,
      gender, and ethnicity.
AB  - Rates of major depressive disorder (MDD) and cigarette smoking increase with
      Latino/a acculturation, but this varies by gender and ethnic subgroup. We
      investigated how lived experiences (i.e., discrimination, family conflict, family
      cohesion, familismo) clustered together in the everyday lives of Latina/os. We
      further examined associations of cluster profile and Latino/a subgroup with MDD
      and smoking, and tested whether gender moderated these associations. Data came
      from the National Latino Asian American Study, which included 2,554 Latino/as (48
      % female; mean age = 38.02 years). K-means cluster analysis revealed six profiles
      of experience, which varied by gender and socio-cultural characteristics.
      Proportionately more women than men were in groups with problematic family lives.
      Acculturated Latino/as were disproportionately represented in profiles reporting
      frequent discrimination, family conflict, and a lack of shared family values and
      cohesion. Profiles characterized by high discrimination and family problems also
      predicted elevated risk for MDD and smoking. Findings suggest that Latino/a
      acculturation comes jointly with increased discrimination, increased family
      conflict, and reduced family cohesion and shared family values, exacerbating risk
      for MDD and smoking. This research on pathways to depression and smoking can
      inform the development of targeted assessment, prevention, and intervention
      strategies, tailored to the needs of Latino/as.

PMID- 22956251
TI  - The EMPOWER study: randomized, prospective, double-blind, multicenter trial of
      vagal blockade to induce weight loss in morbid obesity.
AB  - BACKGROUND: Intermittent, reversible intraabdominal vagal blockade (VBLOC(r)
      Therapy) demonstrated clinically important weight loss in feasibility trials.
      EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted
      in USA and Australia. METHODS: Five hundred three subjects were enrolled at 15
      centers. After informed consent, 294 subjects were implanted with the vagal
      blocking system and randomized to the treated (n = 192) or control (n = 102)
      group. Main outcome measures were percent excess weight loss (percent EWL) at 12
      months and serious adverse events. Subjects controlled duration of therapy using
      an external power source; therapy involved a programmed algorithm of electrical
      energy delivered to the subdiaphragmatic vagal nerves to inhibit
      afferent/efferent vagal transmission. Devices in both groups performed regular,
      low-energy safety checks. Data are mean +/- SEM. RESULTS: Study subjects
      consisted of 90 % females, body mass index of 41 +/- 1 kg/m(2), and age of 46 +/-
      1 years. Device-related complications occurred in 3 % of subjects. There was no
      mortality. 12-month percent EWL was 17 +/- 2 % for the treated and 16 +/- 2 % for
      the control group. Weight loss was related linearly to hours of device use;
      treated and controls with >= 12 h/day use achieved 30 +/- 4 and 22 +/- 8 % EWL,
      respectively. CONCLUSIONS: VBLOC(r) therapy to treat morbid obesity was safe, but
      weight loss was not greater in treated compared to controls; clinically important
      weight loss, however, was related to hours of device use. Post-study analysis
      suggested that the system electrical safety checks (low charge delivered via the
      system for electrical impedance, safety, and diagnostic checks) may have
      contributed to weight loss in the control group.

PMID- 22956252
TI  - Comment on Short-term effects of sleeve gastrectomy and caloric restriction on
      blood pressure in diet-induced obese rats.

PMID- 22956254
TI  - Osteometabolic and osteogenetic pattern of Turkish immigrants in Germany.
AB  - INTRODUCTION: The etiology of osteoporosis comprises environmental and genetic
      factors. This study investigated vitamin D deficiency and specific genetic
      alterations of bone metabolism in a group of 183 Turkish immigrants in Germany in
      comparison with 46 age and sex matched healthy German controls (females in both
      groups were pre-menopausal). METHODS: Bone mineral density (BMD) was measured by
      dual-energy X-ray absorptiometry. Serum levels of osteologic parameters were
      determined after overnight fasting. Polymorphisms of the vitamin D receptor (VDR)
      and lactase genes were genotyped using genomic DNA from peripheral leukocytes.
      Statistical analysis comprised student's t-test, Mann-Whitney rank sum test, Chi
      square analysis and Fisher's exact test. RESULTS: Severe 25-OH D3 hypovitaminosis
      (83.1%) and elevated parathyroid hormone (82%) were common among immigrants.
      Osteoporosis but not osteopenia was more prevalent in immigrants. Among
      immigrants with osteoporosis, TRAP5b was elevated in 26.7%, and beta-crosslaps in
      13.3%. Only the FokI FF VDR-gene-polymorphism was significantly more prevalent
      among immigrants. In contrast, Ff-genotyped Turkish women exhibited significantly
      decreased BMD. Lactase polymorphisms were significantly more common among
      immigrants (84.2% vs. 30.4%) and the CC genotype was commonly associated with
      reduced BMD (41.6%) but rarely osteoporosis (8.4%). CONCLUSIONS: Vitamin D
      deficiency, secondary hyperparathyroidism and osteoporosis are common among
      Turkish immigrants in Germany. Thus, in this population osteologic parameters and
      BMD should be analyzed and deficiencies be treated. Specifically, the VDR gene
      polymorphism FokI Ff is of clinical value in identifying females at risk of
      osteoporosis. In contrast, LCT polymorphisms, though common, do not appear to be
      a risk factor.

PMID- 22956255
TI  - Genetic variants in GCKR, GIPR, ADCY5 and VPS13C and the risk of severe
      sulfonylurea-induced hypoglycaemia in patients with type 2 diabetes.
AB  - OBJECTIVE: Severe hypoglycaemia (SH) induced by sulfonylureas is a life
      threatening condition. We hypothesized that recently identified polymorphisms
      associated with insulin secretion in GCKR, GIPR, ADCY5 and VPS13C genes affect
      the response to sulfonylureas in patients with type 2 diabetes (T2D) and so,
      result in reduced risk for SH. RESEARCH DESIGN AND METHODS: We assessed the
      prevalence of GCKR, GIPR, ADCY5 and VPS13C polymorphisms in a case-control study
      including 111 patients with SH and 100 patients with T2D but without a history of
      SH. All patients were treated with the sulfonylurea drugs glimepiride,
      glibenclamide or gliquidon. SH was defined as a symptomatic event with blood
      glucose of <50 mg/dl requiring treatment with intravenous glucose. RESULTS: In
      logistic regression analyses, a low HbA(1c) and a higher sulfonylurea dose
      appeared to be the only predictors of SH (P=0.001 and P=0.04, respectively).
      There was no significant difference in the genotype distribution between the
      control group and the cases with SH for any of the investigated polymorphisms (OR
      and 95% confidence intervals - 0.90 (0.59-1.38) for GCKR; 1.11 (0.67-1.85) for
      GIPR; 0.75 (0.48-1.17) for ADCY5; 1.43 (0.95-2.15) for VPS13C; all P-values
      >0.05). Also, there was no significant effect of the examined genetic variants on
      HbA1c levels (all P-values >0.05 adjusted for age, sex, BMI, diabetes duration,
      sulfonylurea dose). CONCLUSIONS: We found no detectable effect (with an OR >2.1)
      of the variants in GCKR, GIPR, ADCY5 and VPS13C on the response to sulfonylurea
      treatment, indicating that these variants are not significantly contributing to
      the risk of SH in patients with T2D.

PMID- 22956256
TI  - RIP140 is associated with subclinical inflammation in type 2 diabetic patients.
AB  - AIMS: To evaluate the expression level of RIP140 (receptor interaction protein
      140) and its correlation with inflammatory cytokine production and free fatty
      acids (FFAs) in type 2 diabetes. METHODS: Plasma and peripheral blood mononuclear
      cells (PBMCs) were collected from 24 diabetic and 30 healthy individuals. The
      levels of FFAs, TC, TG, HDL-C, LDL-C, FIN, and FBG were measured. The insulin
      resistance index was calculated using the homeostasis model assessment (HOMA).
      Additionally, PBMCs from control group were cultured alone or with 500 MUmol/L
      palmitic acid (PA). Levels of RIP140 TNF-alpha, and IL-6 in PBMCs were analyzed
      using real-time RT-PCR, Western blots and ELISA. The relationship between RIP140
      and other variables was performed using SPSS 11.5 software. RESULTS: TG, LDL-C,
      FIN, FBG, HOMA, and HDL-C were significantly different between diabetic patients
      and the control group. Levels of RIP140, TNF-alpha, and IL-6 were higher in the
      diabetic group compared to control. RIP140 expression was positively correlated
      with FFAs, HDL-c, TNF-alpha, IL-6, FIN, FBG, and HOMA. Finally, 500 MUmol/L PA
      treatment increased RIP140 expression and the secretion of inflammatory cytokines
      in cultured control PBMCs. CONCLUSIONS: Increased RIP140 level may be closely
      associated with inflammation and disorder of lipid and glucose metabolism in
      diabetic patients.

PMID- 22956257
TI  - MiRNA-21 reverses high glucose and high insulin induced insulin resistance in 3T3
      L1 adipocytes through targeting phosphatase and tensin homologue.
AB  - AIMS/HYPOTHESIS: Our previous study showed there was a change of microRNA (miRNA)
      expression profile, and miR-21 was significantly down regulated in insulin
      resistant adipocytes (IR-adipocytes). Phosphatase and tensin homologs deleted on
      chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase
      (PI3K)/AKT pathway, was identified to be a target gene of miR-21, which suggested
      miR-21 might be associated with insulin resistance (IR) or diabetes. However, it
      is not known whether miR-21 play any role in the development of IR in 3T3-L1
      adipocytes. METHODS: Normal adipocytes and adipocytes transfected with pre-miR
      21(pmiR-21) or negative control (pNeg) were treated with high glucose and high
      insulin for 24 h, insulin-stimulated glucose uptake was determined by 2
      Deoxyglucose transport assay, miR-21 expression level was measured by using
      quantitative real-time RT-PCR (qRT-PCR). The protein expression levels of PTEN,
      Akt, phospho-Akt (Ser473), IRbeta, GSK3beta, phospho-GSK3beta (Ser9) and GLUT4
      were detected by western blotting assay. RESULTS: We further confirmed that miR
      21 was down regulated in IR-adipocytes by qRT-PCR. Over-expression of miR-21
      significantly increased insulin-induced glucose uptake and decreased PTEN protein
      expression, while it had no significant effect on PTEN mRNA expression in IR
      adipocytes. Moreover, over-expressing miR-21 significantly increased insulin
      induced phosphorylation of AKT (Ser473), GSK3beta (Ser9) and the translocation of
      glucose transporter 4 (GLUT4) in IR-adipocytes. CONCLUSIONS: In this study, our
      data demonstrate that miR-21 reverses high glucose and high insulin induced IR in
      3T3-L1 adipocytes, possibly through modulating the PTEN-AKT pathway, and miR-21
      may be a new therapeutic target for metabolic diseases such as T2DM and obesity.

PMID- 22956258
TI  - Life-long weight change can predict metabolic diseases. Retrospective primary
      care study on the weight gain differences between elderly patients with diabetes
      and hypertension.
AB  - BACKGROUND: Patients with diabetes and hypertension represent a large proportion
      of primary care patients. Evaluation of their parameters usually requires medical
      setting, body weight and height can be measured by the patients themselves and
      this is often the case. The aim of this retrospective study is to analyse and to
      compare the life-long data on weight and BMI of patients with diabetes and
      hypertension and those without these pathologic conditions. PATIENTS: Eventually
      selected 759 patients (337 men, 422 women) between 60 and 70 years of age in
      different primary care settings were involved. METHODS: Retrospective and recent
      self-recorded data on weight and height in every decade since the age of 20 years
      in both genders were collected. These were compared to the control group of
      persons free from diabetes and hypertension. RESULTS: The current body weight and
      BMI were significantly higher in all groups than at 20 years and less than their
      maximal values. Patients with diabetes started at higher weights and their
      greatest gain was observed between 20-30 years in men and between 30-40 years in
      women, and in the last decade prior to diagnosis in both genders. Weight gain in
      the control group was steady at a lower rate. CONCLUSIONS: Higher increases in
      body weight in the early youth decades were related to elevated hazard ratios for
      diabetes in men and for hypertension in women. More research with standardized
      methodology is needed to explore this relationship better: meanwhile more
      contribution is expected from primary care physicians in the weight management of
      their younger patients.

PMID- 22956259
TI  - A micro-imaging study linking bone cancer pain with tumor growth and bone
      resorption in a rat model.
AB  - Bone metastases represent a frequent complication of advanced breast cancer. As
      tumor growth-induced bone remodeling progresses, episodes of severe pain and
      fractures of weight-bearing limbs increase. All of these skeletal-related events
      influence the patient's quality of life and survival. In the present study, we
      sought to determine whether some of these pain-related behaviors could be
      directly correlated to tumor progression and bone remodeling. For this purpose,
      we used a rat model of bone cancer pain based on the implantation of mammary
      carcinoma cells in the medullary cavity of the femur. The bone content and tumor
      growth were monitored over time by magnetic resonance imaging (MRI) and micro X
      ray computed tomography (MUCT). The same animals were evaluated for changes in
      their reflexive withdrawal responses to mechanical stimuli (allodynia) and weight
      bearing deficits. As assessed by MRI, we found a negative correlation between
      tumor volume and allodynia or postural deficits throughout the experiment. Using
      MUCT, we found that the bone volume/total volume (BV/TV) ratios for trabecular
      and cortical bone correlated with both mechanical hypersensitivity and weight
      bearing impairment. However, whereas trabecular BV/TV stabilized between days 7
      and 10 post-tumor detection, the cortical bone loss reached its maximum at that
      time. Our imaging approach also allowed us to consistently detect the tumor
      before the onset of pain, paving the way for the preemptive identification of at
      risk patients. Altogether, these results improve our understanding of the events
      leading to tumor-induced bone pain and could eventually help in the design of
      novel strategies for the management of bone diseases.

PMID- 22956260
TI  - Skewed immunological balance between Th17 (CD4(+)IL17A (+)) and Treg (CD4 (+)CD25
      (+)FOXP3 (+)) cells in human oral squamous cell carcinoma.
AB  - BACKGROUND: Several studies have documented modulation of Th17 and T regulatory
      (Treg) cells in various human malignancies which may vary with the type and
      extent of the disease. However, such data in patients with oral cancer is scarce
      and hence the current study was designed to elaborate the immunological balance
      between these two T cell subsets in oral cancer. METHODS AND RESULTS: We analyzed
      various T cell subsets in the peripheral blood of 45 oral squamous cell carcinoma
      (OSCC) patients and 40 healthy volunteers. We found that, compared with the
      healthy controls, patients had a significantly (p < 0.0001) higher proportion of
      both Th17 (CD4(+)IL17A(+)) and Treg (CD4(+)CD25(+)FOXP3(+)) cells, which further
      showed a reciprocal balance in relation to clinico-pathological parameters in
      patients. We also detected a circulating CD8(+) subset of these cells in both
      patients and healthy controls, although the difference between the two groups was
      statistically insignificant. Higher frequencies of Th17 cells were found in
      patients with early stages and without lymph node involvement, while an increased
      prevalence of Tregs was associated with higher clinical stages and lymph node
      involvement. Moreover, Th17 cells were quantitatively and positively correlated
      to CD4(+)T and CD8(+)T cells and inversely correlated with Tregs. Contrarily,
      Tregs showed a negative association with CD4(+)T and CD8(+)T cells. CONCLUSIONS:
      Our results suggest an increase in Th17/Tregs ratio in early stages and a
      decrease in this ratio in higher stages of oral cancer. Such counter regulation
      of Th17 and Tregs may be a significant prognostic factor in oral cancer patients.

PMID- 22956262
TI  - Quality of life and survival in patients with advanced kidney failure managed
      conservatively or by dialysis.
AB  - BACKGROUND AND OBJECTIVES: Benefits of dialysis in elderly dependent patients are
      not clearcut. Some patients forego dialysis, opting for conservative kidney
      management (CKM). This study prospectively compared quality of life and survival
      in CKM patients and those opting for dialysis. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Quality-of-life assessments (Short-Form 36, Hospital Anxiety and
      Depression Scale, and Satisfaction with Life Scale) were performed every 3 months
      for up to 3 years in patients with advanced, progressive CKD (late stage 4 and
      stage 5). RESULTS: After 3 years, 80 and 44 of 170 patients had started or were
      planned for hemodialysis (HD) or peritoneal dialysis, respectively; 30 were
      undergoing CKM; and 16 remained undecided. Mean baseline estimated GFR +/- SD was
      similar (14.0 +/- 4.0 ml/min per 1.73 m(2)) in all groups but was slightly higher
      in undecided patients. CKM patients were older, more dependent, and more highly
      comorbid; had poorer physical health; and had higher anxiety levels than the
      dialysis patients. Mental health, depression, and life satisfaction scores were
      similar. Multilevel growth models demonstrated no serial change in quality-of
      life measures except life satisfaction, which decreased significantly after
      dialysis initiation and remained stable in CKM. In Cox models controlling for
      comorbidity, Karnofsky performance scale score, age, physical health score, and
      propensity score, median survival from recruitment was 1317 days in HD patients
      (mean of 326 dialysis sessions) and 913 days in CKM patients. CONCLUSIONS:
      Patients choosing CKM maintained quality of life. Adjusted median survival from
      recruitment was 13 months shorter for CKM patients than HD patients.

PMID- 22956261
TI  - Aberrant microRNA expression and its implications in the pathogenesis of
      leukemias.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of non-coding, endogenous, small RNAs
      that negatively regulate gene expression by inducing degradation or translational
      inhibition of target mRNAs. Aberrant expression of miRNAs appears to be a common
      characteristic of hematological malignancies including leukemias. AIM: Here we
      review the available data supporting a role of aberrant expression of miRNAs in
      the pathogenesis of leukemias including acute myeloid leukemia (AML), acute
      lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic
      lymphocytic leukemia (CLL). CONCLUSIONS: The expression signatures of miRNAs
      provide exciting opportunities in the diagnosis, prognosis, and therapy of
      leukemia. Since miRNAs can function as either oncogenes or tumor suppressor genes
      in leukemogenesis, the potential of using these small RNAs as therapeutic targets
      opens up new opportunities for leukemia therapy by either inhibiting or
      augmenting their activity.

PMID- 22956263
TI  - Factors in career choice among US nephrologists.
AB  - BACKGROUND AND OBJECTIVES: There is a projected shortage of kidney specialists,
      and retention of trainees in nephrology is important. Determining factors that
      result in choosing a nephrology career could inform future strategies to attract
      nephrology fellows. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: An anonymous,
      internet-based survey was sent to members of the American Society of Nephrology
      in June 2009. Respondents answered questions about demographics, training
      background, and career choices. RESULTS: Of the 3399 members, 913 (23%) returned
      the survey. Mean age was 51.1 +/- 10.5 years, and 46.1% were academic
      nephrologists. In addition, 38.4% of respondents graduated between 2000 and 2009.
      Interest in nephrology began early in training, with the intellectual aspects of
      nephrology, early mentoring, and participation in nephrology electives named as
      the most common reasons in choosing nephrology. Academic nephrologists were more
      likely to have participated in research in medical school, have a master's degree
      or PhD, and successfully obtained research funding during training. Academic debt
      was higher among nonacademic nephrologists. Research opportunities and
      intellectual stimulation were the main factors for academic nephrologists when
      choosing their first postfellowship positions, whereas geographic location and
      work-life balance were foremost for nonacademic nephrologists. CONCLUSIONS: These
      findings highlight the importance of exposing medical students and residents to
      nephrology early in their careers through involvement in research, electives, and
      positive mentoring. Further work is needed to develop and implement effective
      strategies, including increasing early exposure to nephrology in preclinical and
      clinical years, as well as encouraging participation in research, in order to
      attract future nephrology trainees.

PMID- 22956264
TI  - Familial factors in the association between preeclampsia and later ESRD.
AB  - BACKGROUND AND OBJECTIVES: Women with preeclampsia have increased risk of
      developing ESRD. This study assessed whether this can be explained by
      preeclampsia itself or by familial aggregation of common risk factors. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Since 1967, the Medical Birth Registry of
      Norway has registered data on all births in the country. By linkage with the
      Norwegian Population Registry, different, but overlapping, cohorts were defined:
      the first and second cohorts included women and a sibling (first cohort) or child
      (second cohort) with a registered first birth between 1967 and 2008. Similar
      cohorts were defined for men. The Norwegian Renal Registry provided data on ESRD
      from 1980 to June 2009. RESULTS: Cohort 1 was used for the main analyses and
      included 570,675 women, 291 of whom developed ESRD after a median 18.2 years.
      Compared with women without preeclampsia and no siblings with preeclampsia, women
      without preeclampsia but a sibling with preeclampsia had a relative risk (RR) of
      ESRD of 0.96 (95% confidence interval, 0.59-1.6), women with preeclampsia but no
      siblings with preeclampsia had a RR of 6.0 (4.4-8.1), and women with preeclampsia
      and a sibling with preeclampsia had a RR of 2.8 (0.88-8.6). Further analyses of
      women showed no increased risk of ESRD if a child had preeclampsia in first
      pregnancy. CONCLUSIONS: Familial aggregation of risk factors does not seem to
      explain increased ESRD risk after preeclampsia. These findings support the
      hypothesis that preeclampsia per se may lead to kidney damage.

PMID- 22956265
TI  - Association of pre-kidney transplant markers of mineral and bone disorder with
      post-transplant outcomes.
AB  - BACKGROUND AND OBJECTIVES: Mineral and bone disorders (MBDs) are common in long
      term dialysis patients and are risk factors for unfavorable outcomes. The
      associations between pretransplant levels of MBD surrogates and outcomes after
      kidney transplantation are not clear. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Data from the Scientific Registry of Transplant Recipients up to
      June 2007 were linked to the 5-year (July 2001-June 2006) cohort of a large
      dialysis organization in the United States. All dialysis patients who received a
      kidney transplant during this period were identified and divided into groups
      according to increments of pretransplant MBD markers. Unadjusted and multivariate
      adjusted predictors of transplant outcomes were examined. RESULTS: The 11,776
      patients were aged 47 +/- 14 years and 39% were women. Compared with recipients
      with pretransplant time-averaged serum alkaline phosphatase of 80-120 U/L,
      recipients with pretransplant serum alkaline phosphatase of 120-160 and >=160 U/L
      had 49% and 64% higher graft failure censored all-cause mortality in
      multivariable adjusted models. There was no significant association between time
      averaged serum alkaline phosphatase categories and risk of death censored graft
      failure, delayed graft function (DGF), or acute rejection (AR). Compared with
      recipients with pretransplant time-averaged serum parathyroid hormone (PTH)
      levels of 150-300 pg/ml, there was no significant association with graft censored
      death among recipients with pretransplant serum PTH >=800 pg/ml. In addition, the
      risk of graft failure, DGF, and AR did not show any association with time
      averaged serum intact PTH level. There was no significant association between
      time-averaged serum calcium categories and risk of graft failure censored death,
      DGF, and AR. CONCLUSIONS: In this cohort, hemodialysis patients with
      pretransplant serum alkaline phosphatase >120 U/L have unfavorable post
      transplant mortality, whereas there was no association between serum PTH and
      serum calcium levels and post-transplant outcomes.

PMID- 22956266
TI  - Peritoneal dialysis-associated peritonitis with simultaneous exit-site infection.
AB  - With the implementation of best demonstrated clinical practices, peritonitis has
      become an infrequent complication of peritoneal dialysis in many centers around
      the world. Yet the gains in reduction in risk of peritonitis are not uniform.
      Most episodes of peritonitis do not require hospitalization and it is possible to
      achieve cure rates of 70%-80%. Some circumstances, however, necessitate the
      removal of the peritoneal dialysis catheter. These include patients with
      inadequate response to antimicrobial therapy, those with fungal peritonitis, or
      those with Staphylococcus aureus or Pseudomonas peritonitis with coexisting exit
      site infection with the same organism. If the peritoneal dialysis catheter is
      removed in the presence of active intraperitoneal infection, replacement of the
      peritoneal dialysis catheter should be deferred by 2-4 weeks. However,
      simultaneous removal and replacement is possible in selected circumstances such
      as in patients with S. aureus or Pseudomonas peritonitis who also have exit-site
      infection with the same organism, after the intraperitoneal infection has
      responded to antibiotic therapy.

PMID- 22956267
TI  - The wire and urban health education.
AB  - As urban health has emerged as a distinct field, experts have collaborated to
      develop models for interdisciplinary education to train health professionals.
      Interdisciplinary learning is an important yet challenging imperative for urban
      health education. This paper explores lessons learned from a 2010 speaker series
      at the Johns Hopkins Bloomberg School of Public Health. The television show, The
      Wire, was used as a teaching tool to illustrate the context of health disparities
      in American cities and to explore the complex factors perpetuating urban health
      outcomes. We suggest that individuals interested in developing interdisciplinary
      teaching models can learn from both the form and the content of The Wire. As a
      popular televised serial narrative, The Wire prompts an investigation into the
      forms and circulation of academic research in a fractured and specialized media
      landscape. The formal narrative structure of the show provides mental scaffolding
      from which epidemiological, historical, geographical, anthropological, and other
      relevant disciplinary learning can build. The Wire encourages critical reflection
      among public health professionals about the forces that shape public health
      training, research, and practice and offers creative expansions to existing urban
      health educational efforts.

PMID- 22956268
TI  - Evaluation of sonoanatomy relevant to performing stellate ganglion blocks using
      anterior and lateral simulated approaches: an observational study.
AB  - PURPOSE: Stellate (cervicothoracic) ganglion block (SGB) can be associated with
      serious complications, such as esophageal and vascular injury. The objective of
      this study was to evaluate the potential for vascular and esophageal injury in
      healthy subjects by examining the sonoanatomy of the neck relevant to the SGB at
      the sixth (C6) and seventh (C7) cervical vertebral levels and determining the
      incidence of blood vessels and esophagi in the simulated path of needle insertion
      in the conventional and two different ultrasound-guided approaches used to
      perform a SGB. METHODS: Ultrasound scanning of the neck at the C6 and C7 cervical
      vertebral levels was performed in 100 adult subjects, and the following
      measurements were obtained: the degree of deviation of the esophagus relative to
      the larynx/trachea; the likelihood of encountering a vessel in the simulated path
      of needle insertion in the two different approaches to SGB; the incidence of the
      vertebral artery being situated outside the foramen transversarium at the C6
      level; and the distance of the simulated path of needle insertion in the anterior
      and lateral approaches to SGB at the C6 level. RESULTS: The position of the
      esophagus was found to be variable but lateral to the airway in 50% and 74% of
      the subjects at C6 and C7, respectively. The esophagus covered more than half of
      the distance between the airway and the carotid artery in 14% and 44% of the
      subjects at the C6 and C7 levels, respectively. With the anterior approach, a
      major vessel was observed in up to 29% and 43% of patients at the C6 and C7
      levels, respectively. The vertebral artery was outside the foramen transversarium
      in 7% of subjects at the C6 level. CONCLUSION: Major blood vessels and the
      esophagus are in close proximity to needle pathways during the anterior approach
      to SGB performed with either anatomic landmarking or fluoroscopic guidance. An
      ultrasound-guided lateral approach at the C6 level may possibly confer a greater
      margin of safety for performing SGB.

PMID- 22956269
TI  - Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster
      (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status
      during pregnancy to influence birth weight.
AB  - Maternal smoking during pregnancy is associated with low birth weight. Common
      variation at rs1051730 is robustly associated with smoking quantity and was
      recently shown to influence smoking cessation during pregnancy, but its influence
      on birth weight is not clear. We aimed to investigate the association between
      this variant and birth weight of term, singleton offspring in a well-powered meta
      analysis. We stratified 26 241 European origin study participants by smoking
      status (women who smoked during pregnancy versus women who did not smoke during
      pregnancy) and, in each stratum, analysed the association between maternal
      rs1051730 genotype and offspring birth weight. There was evidence of interaction
      between genotype and smoking (P = 0.007). In women who smoked during pregnancy,
      each additional smoking-related T-allele was associated with a 20 g [95%
      confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in
      women who did not smoke during pregnancy, the effect size estimate was 5 g per T
      allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during
      pregnancy modifies the association between maternal rs1051730 genotype and
      offspring birth weight. This strengthens the evidence that smoking during
      pregnancy is causally related to lower offspring birth weight and suggests that
      population interventions that effectively reduce smoking in pregnant women would
      result in a reduced prevalence of low birth weight.

PMID- 22956271
TI  - Neuroinflammation and proteostasis are modulated by endogenously biosynthesized
      neuroprotectin D1.
AB  - Neurodegenerative diseases encompass complex cell signaling disturbances that
      initially damage neuronal circuits and synapses. Due to multiple protective
      mechanisms enacted to counteract the onset of neurodegenerative diseases, there
      is often a prolonged period without noticeable impairments during their
      initiation. Since severe cognitive deficit or vision loss takes place after that
      period there is an opportunity to harness endogenous protective mechanisms as
      potential therapeutic approaches. The activation of the biosynthesis of the
      docosanoid mediator neuroprotectin D1 (NPD1) is an early response to the upsurge
      of protein misfolding and other neuroinflammatory events. This overview discusses
      the potent neuroprotective and inflammation-modulating bioactivity of NPD1. This
      lipid mediator represents an early response to neurodegenerations, aiming to
      restore homeostasis.

PMID- 22956270
TI  - Mouse models of polyglutamine diseases: review and data table. Part I.
AB  - Polyglutamine (polyQ) disorders share many similarities, such as a common
      mutation type in unrelated human causative genes, neurological character, and
      certain aspects of pathogenesis, including morphological and physiological
      neuronal alterations. The similarities in pathogenesis have been confirmed by
      findings that some experimental in vivo therapy approaches are effective in
      multiple models of polyQ disorders. Additionally, mouse models of polyQ diseases
      are often highly similar between diseases with respect to behavior and the
      features of the disease. The common features shared by polyQ mouse models may
      facilitate the investigation of polyQ disorders and may help researchers explore
      the mechanisms of these diseases in a broader context. To provide this context
      and to promote the understanding of polyQ disorders, we have collected and
      analyzed research data about the characterization and treatment of mouse models
      of polyQ diseases and organized them into two complementary Excel data tables.
      The data table that is presented in this review (Part I) covers the behavioral,
      molecular, cellular, and anatomic characteristics of polyQ mice and contains the
      most current knowledge about polyQ mouse models. The structure of this data table
      is designed in such a way that it can be filtered to allow for the immediate
      retrieval of the data corresponding to a single mouse model or to compare the
      shared and unique aspects of many polyQ models. The second data table, which is
      presented in another publication (Part II), covers therapeutic research in mouse
      models by summarizing all of the therapeutic strategies employed in the treatment
      of polyQ disorders, phenotypes that are used to examine the effects of the
      therapy, and therapeutic outcomes.

PMID- 22956273
TI  - Protein tyrosine phosphatase sigma in proteoglycan-mediated neural regeneration
      regulation.
AB  - The receptor-type protein tyrosine phosphatase PTPsigma mediates neural
      development and regeneration. Early studies on the ligands of PTPsigma identified
      heparan sulfate proteolycan (HSPG) as a ligand. Binding of HSPG to PTPsigma plays
      a critical role in axon guidance and synapse formation. PTPsigma is also a
      receptor for chondroitin sulfate proteoglycan (CSPG). CSPG is deposited in high
      concentration at sites of neural injury. The deposited CSPG inhibits neural
      regeneration and axonal growth via PTPsigma. The crystal structure of N-terminal
      immunoglobulin-like domains of PTPsigma shows that the glycan binding site forms
      an elliptical surface patch of ~35 by 24 A, which interacts with sulfate groups
      of HSPG and CSPG. In this review, we focus on the structural and functional
      mechanisms for the neural regeneration regulation by different types of
      proteoglycans. We also discuss recent results on induction of neural regeneration
      in the stroke model and neural transplantation. The mechanistic understanding of
      relationships between proteoglycans and PTPsigma provides new therapeutic
      opportunities against diseases with impaired neural regeneration.

PMID- 22956275
TI  - Extraction and purification of purple membrane for photochromic thin film
      development: application in photoelectrochemical investigation.
AB  - Purple membrane (PM) has been extracted and purified from archaebacteria for thin
      film development. The purified purple membrane is isolated in 1 % polyvinyl
      alcohol solution for making thin film within gelatin and organically modified
      silicate matrices. For thin film within gelatin matrix, homogenized purple
      membrane suspension is mixed with 8 % gelatin and poured into a specially
      designed block with desired thickness of spacer having hydrophobicity followed by
      gelatinization of the same over home-made thermostatic control unit at 38 
      degrees C. The gelatinized matrix is then allowed to dry under controlled
      conditions of humidity and temperature. The films of varying thicknesses ranging
      between 40, 50, and 60 MU are used for photo-electrochemical measurements. The
      results on photo-electrochemistry of non-oriented purple membrane film provides
      valuable information on the generation of forward (light on) and backward (light
      off) photocurrent as a function of: (a) applied potential and (b) film thickness.
      An increase in applied negative potential increases the amplitude of photocurrent
      whereas decrease in film thickness facilitates the reversibility of photocurrent
      response.

PMID- 22956274
TI  - Peer victimization in childhood and internalizing problems in adolescence: a
      prospective longitudinal study.
AB  - Traumatic childhood experiences have been found to predict later internalizing
      problems. This prospective longitudinal study investigated whether repeated and
      intentional harm doing by peers (peer victimization) in childhood predicts
      internalizing symptoms in early adolescence. 3,692 children from the Avon
      Longitudinal Study of Parents and Children (ALSPAC), as well as their mothers and
      teachers, reported on bullying in childhood (7-10 years) and internalizing
      problems in early adolescence (11-14 years). Controlling for prior
      psychopathology, family adversity, gender and IQ, being a victim of bullying was
      associated with higher overall scores, as well as increased odds of scoring in
      the severe range (>90(th) percentile) for emotional and depression symptoms.
      Victims were also more likely to show persistent depression symptoms over a 2
      year period. These associations were found independent of whether mothers,
      teachers or the children reported on bullying. It is concluded that peer
      victimization in childhood is a precursor of both short-lived and persistent
      internalizing symptoms, underlining the importance of environmental factors such
      as peer relationships in the etiology of internalizing problems.

PMID- 22956276
TI  - New tools for exploring "old friends-microbial lipases".
AB  - Fat-splitting enzymes (lipases), due to their natural, industrial, and medical
      relevance, attract enough attention as fats do in our lives. Starting from the
      paper that we write, cheese and oil that we consume, detergent that we use to
      remove oil stains, biodiesel that we use as transportation fuel, to the
      enantiopure drugs that we use in therapeutics, all these applications are
      facilitated directly or indirectly by lipases. Due to their uniqueness,
      versatility, and dexterity, decades of research work have been carried out on
      microbial lipases. The hunt for novel lipases and strategies to improve them
      continues unabated as evidenced by new families of microbial lipases that are
      still being discovered mostly by metagenomic approaches. A separate database for
      true lipases termed LIPABASE has been created recently which provides taxonomic,
      structural, biochemical information about true lipases from various species. The
      present review attempts to summarize new approaches that are employed in various
      aspects of microbial lipase research, viz., screening, isolation, production,
      purification, improvement by protein engineering, and surface display. Finally,
      novel applications facilitated by microbial lipases are also presented.

PMID- 22956272
TI  - Insulin in the brain: sources, localization and functions.
AB  - Historically, insulin is best known for its role in peripheral glucose
      homeostasis, and insulin signaling in the brain has received less attention.
      Insulin-independent brain glucose uptake has been the main reason for considering
      the brain as an insulin-insensitive organ. However, recent findings showing a
      high concentration of insulin in brain extracts, and expression of insulin
      receptors (IRs) in central nervous system tissues have gathered considerable
      attention over the sources, localization, and functions of insulin in the brain.
      This review summarizes the current status of knowledge of the peripheral and
      central sources of insulin in the brain, site-specific expression of IRs, and
      also neurophysiological functions of insulin including the regulation of food
      intake, weight control, reproduction, and cognition and memory formation. This
      review also considers the neuromodulatory and neurotrophic effects of insulin,
      resulting in proliferation, differentiation, and neurite outgrowth, introducing
      insulin as an attractive tool for neuroprotection against apoptosis, oxidative
      stress, beta amyloid toxicity, and brain ischemia.

PMID- 22956277
TI  - Production of the antimicrobial protein weisselin A by Weissella
      paramesenteroides DX in batch fermentations: the type of carbohydrate used as the
      C-source in the substrate affects the association of production with growth.
AB  - The effect of the type of carbohydrate (glucose, fructose, sucrose or galactose)
      used as the carbon source in the substrate on weissellin A production by
      Weissella paramesenteroides DX was evaluated on a solid-state cultivation
      procedure and conventional batch fermentations. Solid-state cultivation was done
      on M17-based medium over 3- and 6-h incubation periods. Experimental data showed
      that glucose supports the highest production levels on a per cell basis. Stirred
      tank bioreactor fermentations carried out at 50 % dissolved oxygen tension
      revealed the superiority of glucose over the other carbohydrates. Glucose
      supports growth-associated production and increased production rates and
      productivities (1,120 AU/ml). Growth-associated production was maintained with
      fructose but with lower fermentation rates and productivities. Sucrose cannot
      support this type of production. Fermentations with sucrose were characterized of
      lower sugar uptake rates, and lower specific growth and production rates, with
      bacteriocin titres not exceeding 630 AU/ml, while product formation kinetics were
      of the intermediate type.

PMID- 22956278
TI  - Comparative metabolomic study of Penicillium chrysogenum during pilot and
      industrial penicillin fermentations.
AB  - Comparative metabolomics was carried out to investigate the metabolic differences
      of Penicillium chrysogenum in the pilot and industrial fermentations that
      resulted from the scale-up. By principal component analysis, the early stages of
      two fermentation processes were clearly distinguished, whereas the middle and
      final stages were clustered together. It indicated that the different metabolisms
      of cells in the pilot and industrial fermentations mainly existed during the
      early stage. Furthermore, the levels of polyamines, polyols, glycolysis, and
      tricarboxylic acid cycle intermediates, which changed more dramatically during
      the pilot process, were all higher in the pilot than in the industrial
      fermentation during the early stage. This indicated that the fermentation
      conditions of the early stage should be the focus of process management which is
      aimed at increasing penicillin production. Additionally, the comparative
      accumulations of the precursors of penicillin (valine, cysteine, and lysine)
      revealed that penicillin biosynthesis in the industrial process was more affected
      during the middle stage of fermentation. These findings provide new insights to
      further regulate the industrial process and improve the production of penicillin.
      More generally, this study attempts to address the scarcity of studies that
      contrast the metabolic outcomes between commercial- and pilot-scale conditions.

PMID- 22956279
TI  - Animal bone char solubilization with itaconic acid produced by free and
      immobilized Aspergillus terreus grown on glycerol-based medium.
AB  - Cells of Aspergillus terreus, free and immobilized in polyurethane foam, were
      employed in itaconic acid fermentation processes on glycerol-based media. The
      purpose was to assess their suitability for animal bone char solubilization and
      the development of a biotechnological alternative to P fertilizers chemically
      produced from rock phosphate. Animal bones constitute a renewable source of P
      that can replace the traditionally used finite, nonrenewable rock phosphate as a
      P source. Glycerol was an excellent substrate for growth (10.2 g biomass L(-1))
      and itaconic acid production (26.9 g L(-1)) by free fungal cells after 120-h
      fermentation. Simultaneously, A. terreus solubilized the insoluble phosphate to a
      yield of 23 to 50 %, depending on the particle size and concentration.
      Polyurethane foam cut into cubes of 0.5-0.6 cm per side, with 0.3 mm pore size
      and applied at 2.0 g L(-1) proved to be an excellent cell carrier. In repeated
      batch fermentation, the immobilized mycelium showed a high capacity to solubilize
      animal bone char, which resulted on average in 168.8 mg L(-1) soluble phosphate
      per 48-h cycle and 59.4 % yield (percent of total phosphate) registered in the
      fourth batch.

PMID- 22956281
TI  - Thoracic and cardiovascular surgery in Japan during 2010 : annual report by The
      Japanese Association for Thoracic Surgery.

PMID- 22956280
TI  - Overexpression of a putative Arabidopsis BAHD acyltransferase causes dwarfism
      that can be rescued by brassinosteroid.
AB  - Plant growth and development are ensured through networks of complex regulatory
      schemes. Genetic approaches have been invaluable in dissecting these regulatory
      pathways. This study reports the isolation of a semi-dominant dwarf mutant
      designated abnormal shoot1-1 dominant (abs1-1D) through an Arabidopsis T-DNA
      activation tagging mutant screen. It was shown that the overexpression of a novel
      BAHD family acyltransferase gene, ABS1/At4g15400, was the cause of the dwarf
      phenotype in abs1-1D. Overexpression of ABS1 led to many phenotypic features
      reminiscent of brassinosteroid (BR) deficient or signalling mutants, and it was
      shown that exogenously applied BR could effectively rescue the dwarf phenotype of
      abs1-1D. Furthermore, genetic analyses indicated that abs1-1D interacted, in
      different ways, with the BR-deficient mutant det2-1, the constitutive BR response
      mutant bes1-D and the photomorphogenic mutant phyB-1. Moreover, ABS1 expression
      was activated by BR treatment or in a bes1-D mutant background. Genome-wide
      transcriptome profiling of abs1-1D revealed clear reprogramming of metabolic
      pathways, and it was demonstrated that BR biosynthesis genes were activated in
      abs1-1D and that the flavonoid biosynthesis pathway was repressed in abs1-1D, as
      well as in det2-1. This work provides new insights into the possible involvement
      of BAHD acyltransferase in the regulation of plant growth and development, and
      indicates a possible role of ABS1 in maintaining BR homeostasis.

PMID- 22956282
TI  - [Preoperative perfusion analysis before total ankle arthroplasty].
AB  - PURPOSE: Soft tissue management is of paramount importance in ankle surgery. As
      such, full thickness necrosis of the soft tissue envelope represents a severe
      complication following total ankle joint arthroplasty (TAA) potentially leading
      to implant exposure, infection and thus, substantially compromised patient
      outcomes. One of the main factors leading to soft tissue complications is an
      undetermined arterial perfusion of the lower leg or ankle joint. We report on
      clinical cases suffering soft tissue complications following TAA with the
      respective plastic surgical therapy regimen and present a simple algorithm for
      preoperative perfusion evaluation. METHODS: The medical records of 30 consecutive
      primary TAA patients were retrospectively reviewed after observing a higher than
      expected rate of severe soft tissue defects which have been referred to our
      plastic surgery department. RESULTS: 3 patients (10%, all females, age 63 +/- 5
      years; BMI 27 +/- 3 kg/m2) presented with a soft tissue defect leading to
      angiography revealing one case of severe arterial obstruction. Wound closure
      could be reached in one case by conservative therapy consisting of regular
      dressing changes. In the further patients definite soft tissue reconstruction
      could only be performed by surgical intervention. One could be covered by split
      thickness skin grafting and one by a microsurgical transplantation of a free
      latissimus dorsi flap. On the basis of these complications we established an easy
      algorithm for the preoperative evaluation of the arterial perfusion in the ankle
      region. First, (I) the pulses of the dorsal foot artery and posterior tibial
      artery should be examined. In the case of not palpable pulses (II) the ankle
      brachial index should be performed. Values of <0.9 or >1.2 recommend (III) to
      perform angiography. In the case of stenosis or complete obstruction (IV) the
      arterial blood flow should be reconstituted by interventional radiological
      stenting or vascular surgical procedures. CONCLUSION: The identification of the
      arterial perfusion status of patients undergoing TAA using a straightforward
      clinical algorithm might overcome TAA-related soft tissue complications and
      improve patient-related outcome measures.

PMID- 22956283
TI  - [Pelvic reconstruction after tubular rectumresection (extended abdominoperineal
      resection combined with extended transpelvic myocutaneous M. rectus abdominis
      flap (extended VRAM) in low rectum cancer - case series)].
AB  - In advanced lower rectal cancer tubular abdomino-perineal resection (APR) in
      combination with simultaneous extended distally pedicled vertical rectus
      abdominis muscle flap (VRAM) facilitates a more radical tumor resection.
      Additionally a prolapse of small intestine into the pelvis can be blocked and a
      perineal defect coverage can be achieved. 4 patients have been treated with an
      interdisciplinary one stage combined tubular APR and extended VRAM. In all cases
      a R0 resection and a complete defect closure could be achieved.The extended VRAM
      is an appropriate technique to close the pelvic defect because it originates from
      a non irradiated area, has a monitor island, and the donor site does not handicap
      the patient as much as local flaps. This interdisciplinary approach facilitates a
      more radical tumor resection and thus reduces the risk of recurrence.

PMID- 22956284
TI  - [One-stage reconstruction of facial defects after tumor resection with the
      Integra system].
AB  - BACKGROUND: In 2010 excellent aesthetic results after basal cell carcinoma
      excision and one-stage coverage with Integra without split thickness skin graft
      (STSG) were published in a series of 10 Asian patients. Our aim in this study was
      to verify these results in a series of Caucasian patients and evaluate this
      procedure as a possible new standard. PATIENTS AND METHODS: 6 patients with
      facial basal cell carcinoma were treated by regular excision with 3 mm safety
      margins and one-stage coverage with Integra without STSG, followed by a clinical
      evaluation and fotodocumentation. RESULTS: In 3 patients local infection occurred
      with a complete loss of the Integra. 2 out of these 3 patients showed an
      unaesthetic scar and are considering another surgical approach for correction.
      The other 3 patients had an uneventful course, unfortunately 2 out of these
      patients (67%) developed an unaesthetic scar as well and are also considering
      surgical correction. CONCLUSION: Because of aesthetically unsatisfactory results
      and high infection rates we abandoned this procedure after 6 patients only. Our
      standard remains excision with 3 mm safety margins, histological analysis and one
      stage repair with local facial flaps.

PMID- 22956285
TI  - Enhanced killing of cervical cancer cells by combinations of methyl jasmonate
      with cisplatin, X or alpha radiation.
AB  - Current therapies for treatment of advanced cervical cancer involve the use of
      cisplatin, often in combination with radiotherapy. These treatments do not lead
      to a high survival rate and furthermore, serious side effects are dose-limiting
      factors. Methyl jasmonate (MJ) was recently identified as potent and selective
      cytotoxic agent towards cervical cancer cells. In the present study we evaluated
      the effectiveness of combined treatments of MJ with cisplatin or X-irradiation on
      a variety of cervical cancer cells including SiHa, CaSki, HeLa and C33A.
      Cytotoxicity of alpha particles, emitted from (224)Ra atoms, was also evaluated
      as a single agent and in combination with MJ. Cooperation between MJ and
      cisplatin in reducing cell viability (XTT assays) and survival (clonogenicity
      assays) was exhibited towards several cancer cell lines at a range of combination
      doses. MJ effectively cooperated also with X-ray irradiation, significantly
      lowering the radiation doses required to inhibit cell survival (ID50) of all
      tested cells lines. We show for the first time, that alpha irradiation
      selectively reduced cell viability and survival of cervical cancer cells. Lower
      doses of alpha irradiation were required as compared to X-irradiation to inhibit
      cell survival. Cooperation with MJ was demonstrated in part of the cancer cell
      lines. In conclusion, our studies point to alpha irradiation and MJ, novel
      anticancer agents, as potent candidates for treatment of cervical cancer, in
      single agent regiments and in combination. MJ can be added also to conventional X
      ray and cisplatin therapies to increase their cytotoxic effect while lowering the
      effective dose.

PMID- 22956286
TI  - Expression of matrix macromolecules and functional properties of EGF-responsive
      colon cancer cells are inhibited by panitumumab.
AB  - The epidermal growth factor receptor (EGFR) is a member of the HER family
      receptors and its activation induced by its natural ligand EGF results in colon
      cancer growth and progression. Panitumumab (pmAb) is a fully human IgG2 anti-EGFR
      antibody that blocks the EGFR actions. In the present study, we evaluated the
      effects of pmAb on the EGF-mediated cellular responses in a panel of colon cancer
      cells (HCT-8, HT-29, DLD-1 and HCT-116). HCT-1116 and DLD-1 cells showed no
      significant EGF-dependent cell proliferation; HT-29 and HCT-8 exhibited an EGF
      dependent proliferation, with HCT-8 cells to be the most responsive with
      significant EGFR phosphorylation upon treatment with EGF. The effects of pmAb
      were then evaluated in the most EGF-responsive cells, HCT-8. In that respect,
      pmAb impedes the signaling cascade mediated by EGFR intracellular phosphorylation
      and activity of focal adhesion kinase (FAK) as well as the EGF-induced invasive
      and migratory potential of colon cancer cells. At the level of matrix effectors
      implicated in colon cancer progression we report that pmAb is a potent inhibitor
      of constitute and EGF-mediated gene expression of certain matrix effectors, such
      as membrane-type 1 metalloproteinase (MT1-MMP), extracellular metalloproteinases
      inducer (EMMPRIN), urokinase plasminogen activator (uPA) and syndecan-4. The
      obtained data demonstrated that pmAb is a specific blocker of EGF-mediated EGFR
      activation, resulting in a significant inhibition of colon cancer cell
      proliferation in early stages of growth, migration and invasiveness as well as of
      matrix effector implicated in cancer progression.

PMID- 22956287
TI  - Do humans and nonhuman animals share the grouping principles of the iambic
      trochaic law?
AB  - The iambic-trochaic law describes humans' tendency to form trochaic groups over
      sequences varying in pitch or intensity (i.e., the loudest or highest sounds mark
      group beginnings), and iambic groups over sequences varying in duration (i.e.,
      the longest sounds mark group endings). The extent to which these perceptual
      biases are shared by humans and nonhuman animals is yet unclear. In Experiment 1,
      we trained rats to discriminate pitch-alternating sequences of tones from
      sequences randomly varying in pitch. In Experiment 2, rats were trained to
      discriminate duration-alternating sequences of tones from sequences randomly
      varying in duration. We found that nonhuman animals group sequences based on
      pitch variations as trochees, but they do not group sequences varying in duration
      as iambs. Importantly, humans grouped the same stimuli following the principles
      of the iambic-trochaic law (Exp. 3). These results suggest the early emergence of
      the trochaic rhythmic grouping bias based on pitch, possibly relying on
      perceptual abilities shared by humans and other mammals, whereas the iambic
      rhythmic grouping bias based on duration might depend on language experience.

PMID- 22956288
TI  - Carinal resection using an airway exchange catheter-assisted venovenous ECMO
      technique.

PMID- 22956289
TI  - The variation of acceptable blood products and procedures amongst Jehovah's
      Witness patients: analysis of a hospital pre-transfusion discussion tool.

PMID- 22956290
TI  - Deterministic versus stochastic cell polarisation through wave-pinning.
AB  - Cell polarization is an important part of the response of eukaryotic cells to
      stimuli, and forms a primary step in cell motility, differentiation, and many
      cellular functions. Among the important biochemical players implicated in the
      onset of intracellular asymmetries that constitute the early phases of
      polarization are the Rho GTPases, such as Cdc42, Rac, and Rho, which present high
      active concentration levels in a spatially localized manner. Rho GTPases exhibit
      positive feedback-driven interconversion between distinct active and inactive
      forms, the former residing on the cell membrane, and the latter predominantly in
      the cytosol. A deterministic model of the dynamics of a single Rho GTPase
      described earlier by Mori et al. exhibits sustained polarization by a wave
      pinning mechanism. It remained, however, unclear how such polarization behaves at
      typically low cellular concentrations, as stochasticity could significantly
      affect the dynamics. We therefore study the low copy number dynamics of this
      model, using a stochastic kinetics framework based on the Gillespie algorithm,
      and propose statistical and analytic techniques which help us analyse the
      equilibrium behaviour of our stochastic system. We use local perturbation
      analysis to predict parameter regimes for initiation of polarity and wave-pinning
      in our deterministic system, and compare these predictions with deterministic and
      stochastic spatial simulations. Comparing the behaviour of the stochastic with
      the deterministic system, we determine the threshold number of molecules required
      for robust polarization in a given effective reaction volume. We show that when
      the molecule number is lowered wave-pinning behaviour is lost due to an
      increasingly large transition zone as well as increasing fluctuations in the
      pinning position, due to which a broadness can be reached that is unsustainable,
      causing the collapse of the wave, while the variations in the high and low
      equilibrium levels are much less affected.

PMID- 22956291
TI  - What can neurons do for their brain? Communicate selectivity with bursts.
AB  - Neurons deep in cortex interact with the environment extremely indirectly; the
      spikes they receive and produce are pre- and post-processed by millions of other
      neurons. This paper proposes two information-theoretic constraints guiding the
      production of spikes, that help ensure bursting activity deep in cortex relates
      meaningfully to events in the environment. First, neurons should emphasize
      selective responses with bursts. Second, neurons should propagate selective
      inputs by burst-firing in response to them. We show the constraints are necessary
      for bursts to dominate information-transfer within cortex, thereby providing a
      substrate allowing neurons to distribute credit amongst themselves. Finally,
      since synaptic plasticity degrades the ability of neurons to burst selectively,
      we argue that homeostatic regulation of synaptic weights is necessary, and that
      it is best performed offline during sleep.

PMID- 22956292
TI  - Proprioception and person perception: politicians and professors.
AB  - Social-categorical knowledge is partially grounded in proprioception. In Study 1,
      participants describing "hard" and "soft" politicians, and "hard" and "soft"
      scientists used different "hard" and "soft" traits for the two groups, suggesting
      that the meaning of these traits is context specific. Studies 2 to 4 showed that
      both meanings were supported by hard and soft proprioception. Consistent with
      political stereotypes, perceivers viewing faces while handling a hard ball were
      more likely to categorize them as Republicans rather than as Democrats, compared
      to perceivers viewing the same faces while handling a soft ball (Study 2).
      Similarly, consistent with stereotypes of "hard" and "soft" academic disciplines,
      perceivers were more likely to categorize photographs of professors as physicists
      than historians when handling a hard versus soft ball (Study 3). Finally,
      thinking about Republicans and Democrats led participants to perceive a ball as
      harder or softer, respectively, suggesting that simulating proprioception might
      aid social-categorical thinking (Study 4).

PMID- 22956293
TI  - Big two personality and big three mate preferences: similarity attracts, but
      country-level mate preferences crucially matter.
AB  - People differ regarding their "Big Three" mate preferences of attractiveness,
      status, and interpersonal warmth. We explain these differences by linking them to
      the "Big Two" personality dimensions of agency/competence and communion/warmth.
      The similarity-attracts hypothesis predicts that people high in agency prefer
      attractiveness and status in mates, whereas those high in communion prefer
      warmth. However, these effects may be moderated by agentics' tendency to contrast
      from ambient culture, and communals' tendency to assimilate to ambient culture.
      Attending to such agentic-cultural-contrast and communal-cultural-assimilation
      crucially qualifies the similarity-attracts hypothesis. Data from 187,957 online
      daters across 11 countries supported this model for each of the Big Three. For
      example, agentics-more so than communals-preferred attractiveness, but this
      similarity-attracts effect virtually vanished in attractiveness-valuing
      countries. This research may reconcile inconsistencies in the literature while
      utilizing nonhypothetical and consequential mate preference reports that, for the
      first time, were directly linked to mate choice.

PMID- 22956294
TI  - From primed construct to motivated behavior: validation processes in goal
      pursuit.
AB  - Past research has found that primes can automatically initiate unconscious goal
      striving. Recent models of priming have suggested that this effect can be
      moderated by validation processes. According to a goal-validation perspective,
      primes should cause changes in one's motivational state to the extent people have
      confidence in the prime-related mental content. Across three experiments, we
      provided the first direct empirical evidence for this goal-validation account.
      Using a variety of goal priming manipulations (cooperation vs. competition,
      achievement, and self-improvement vs. saving money) and validity inductions
      (power, ease, and writing about confidence), we demonstrated that the impact of
      goal primes on behavior occurs to a greater extent when conditions foster
      confidence (vs. doubt) in mental contents. Indeed, when conditions foster doubt,
      goal priming effects are eliminated or counter to the implications of the prime.
      The implications of these findings for research on goal priming and validation
      processes are discussed.

PMID- 22956295
TI  - Role of information asymmetry and situational salience in reducing intergroup
      bias: the case of ultimatum games.
AB  - While majority of the literature documents the preponderance of social identity
      related biases in favor of in-group members, this research investigates factors
      that may attenuate the bias. Examining intergroup bias within the realm of
      information availability and accessibility, this research highlights malleability
      of judgments and decisions as a function of social identity in both complete and
      incomplete information situations in the context of ultimatum games. Study 1
      replicates the positive bias toward in-group members even in situations where
      individuals know that the counterpart is behaving unfairly. Study 2 shows that
      the intergroup bias is attenuated for relatively unfavorable offers in incomplete
      information situations. However, the intergroup bias is persistent for relatively
      favorable offers. Study 3 shows that making situational constraints salient also
      attenuates the intergroup bias for relatively favorable offers. Together, the
      findings identify conditions, based on information availability and
      accessibility, under which the intergroup bias can be corrected.

PMID- 22956296
TI  - The Healthy Children, Strong Families intervention: design and community
      participation.
AB  - Healthy Children, Strong Families (HCSF) is a 2-year, community-driven, family
      based randomized controlled trial of a healthy lifestyles intervention conducted
      in partnership with four Wisconsin American Indian tribes. HCSF is composed of 1
      year of targeted home visits to deliver nutritional and physical activity
      curricula. During Year 1, trained community mentors work with 2-5-year-old
      American Indian children and their primary caregivers to promote goal-based
      behavior change. During Year 2, intervention families receive monthly newsletters
      and attend monthly group meetings to participate in activities designed to
      reinforce and sustain changes made in Year 1. Control families receive only
      curricula materials during Year 1 and monthly newsletters during Year 2. Each of
      the two arms of the study comprises 60 families. Primary outcomes are decreased
      child body mass index (BMI) z-score and decreased primary caregiver BMI.
      Secondary outcomes include: increased fruit/vegetable consumption, decreased TV
      viewing, increased physical activity, decreased soda/sweetened drink consumption,
      improved primary caregiver biochemical indices, and increased primary caregiver
      self-efficacy to adopt healthy behaviors. Using community-based participatory
      research and our history of university-tribal partnerships, the community and
      academic researchers jointly designed this randomized trial. This article
      describes the study design and data collection strategies, including outcome
      measures, with emphasis on the communities' input in all aspects of the research.

PMID- 22956297
TI  - Investigating hypervigilance for social threat of lonely children.
AB  - The hypothesis that lonely children show hypervigilance for social threat was
      examined in a series of three studies that employed different methods including
      advanced eye-tracking technology. Hypervigilance for social threat was
      operationalized as hostility to ambiguously motivated social exclusion in a
      variation of the hostile attribution paradigm (Study 1), scores on the Children's
      Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially
      rejecting stimuli (Study 3). The participants were 185 children (11 years-7
      months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8
      months) and 140 children (8 years-10 months to 12 years-10 months) in the three
      studies, respectively. Regression analyses showed that, with depressive symptoms
      covaried, there were quadratic relations between loneliness and these different
      measures of hypervigilance to social threat. As hypothesized, only children in
      the upper range of loneliness demonstrated elevated hostility to ambiguously
      motivated social exclusion, higher scores on the rejection sensitivity
      questionnaire, and disengagement difficulties when viewing socially rejecting
      stimuli. We found that very lonely children are hypersensitive to social threat.

PMID- 22956299
TI  - Antibacterial properties of intestinal phospholipase A2 from the common stingray
      Dasyatis pastinaca.
AB  - Stingray phospholipase A(2) group IIA (SPLA(2)-IIA) was recently isolated and
      purified to homogeneity from the intestine of the common stingray Dasyatis
      pastinaca, suggesting that this enzyme plays an important role in systemic
      bactericidal defense. The present study showed that SPLA(2)-IIA was highly
      bactericidal against Gram-positive bacteria with inhibition zones and minimal
      inhibitory concentration values in the range of 13-25 mm and 2-8 MUg/ml,
      respectively, whereas Gram-negative bacteria exhibited a much higher resistance.
      The bactericidal efficiency of SPLA(2)-IIA was shown to be unaffected by high
      protein and salt concentrations, but dependent upon the presence of calcium ions,
      and then correlated to the hydrolytic activity of membrane phospholipids.
      Importantly, we showed that stingray phospholipase A(2) group IIA presents no
      cytotoxicity after its incubation with MDA-MB-231 cells. SPLA(2)-IIA may be
      considered as a future therapeutic agent against bacterial infections.

PMID- 22956298
TI  - Prospective risk factors for adolescent PTSD: sources of differential exposure
      and differential vulnerability.
AB  - There are two types of risk factors for developing PTSD: factors that increase
      the likelihood of experiencing a potentially traumatizing event and factors that
      increase the likelihood of developing symptoms following such events. Using
      prospective data over a two-year period from a large, diverse sample of urban
      adolescents (n = 1242, Mean age = 13.5), the current study differentiates these
      two sources of risk for developing PTSD in response to violence exposure. Five
      domains of potential risk and protective factors were examined: community context
      (e.g., neighborhood poverty), family risk (e.g., family conflict), behavioral
      maladjustment (e.g., internalizing symptoms), cognitive vulnerabilities (e.g.,
      low IQ), and interpersonal problems (e.g., low social support). Time 1
      interpersonal violence history, externalizing behaviors, and association with
      deviant peers were the best predictors of subsequent violence, but did not
      further increase the likelihood of PTSD in response to violence. Race/ethnicity,
      thought disorder symptoms, and social problems were distinctly predictive of the
      development of PTSD following violence exposure. Among youth exposed to violence,
      Time 1 risk factors did not predict specific event features associated with
      elevated PTSD rates (e.g., parent as perpetrator), nor did interactions between
      Time 1 factors and event features add significantly to the prediction of PTSD
      diagnosis. Findings highlight areas for refinement in adolescent PTSD symptom
      measures and conceptualization, and provide direction for more targeted
      prevention and intervention efforts.

PMID- 22956300
TI  - Stabilization of the cellulase enzyme complex as enzyme nanoparticle.
AB  - The native Celluclast BG cellulase enzyme complex consists of different enzymes
      which can also degrade great substrate molecules as native celluloses. This
      enzyme complex has been covered by a very thin, a few nanometers thick, polymer
      layer, in order to improve its stability. It has been proved that the polymer
      layer around the enzyme molecules does not hinder the digestion as great
      substrates as crystalline cellulose polymer. The stability of the prepared enzyme
      nanoparticles (PE) could significantly be increased comparing to that of the
      native one what was proved by results of the total cellulose activity measured.
      The pretreated enzyme complex holds its activity often a few magnitudes of orders
      longer in time than that of the native enzyme complex (enzyme without
      pretreatment). It retains its activity at least ten times longer than that of the
      native one, at a temperature range between 20 and 37  degrees C. The pretreated
      enzyme complex can have about 50 % of its original activity during 12 h of
      incubation at even 80  degrees C, while the native cellulase one totally lost it
      during 6 h incubation time. The activity of PE has not been significantly reduced
      even at extreme pH values, namely in the pH range of 1.5 to 12.

PMID- 22956301
TI  - Evaluation of metal ions and surfactants effect on cell growth and
      exopolysaccharide production in two-stage submerged culture of Cordyceps
      militaris.
AB  - During the two-stage submerged fermentation of medicinal mushroom Cordyceps
      militaris, it was found that K(+), Ca(2+), Mg(2+), and Mn(2+) were favorable to
      the mycelial growth. The EPS production reached the highest levels in the media
      containing Mg(2+) and Mn(2+). However, Ca(2+) and K(+) almost failed to increase
      significantly exopolysaccharides (EPS) production. Sodium dodecyl sulfate (SDS)
      significantly enhanced EPS production compared with that of without adding SDS
      when SDS was added on static culture stage of two-stage cultivation process. The
      presence of Tween 80 in the medium not only simulated mycelial growth but also
      increased EPS production. By response surface methods (RSM), EPS production
      reached its peak value of 3.28 g/L under optimal combination of 27.6 mM Mg(2+),
      11.1 mM Mn(2+), and 0.05 mM SDS, which was 3.76-fold compared with that of
      without metal ion and surfactant. The results obtained were useful in better
      understanding the regulation for efficient production of EPS of C. militaris in
      the two-stage submerged culture.

PMID- 22956302
TI  - A two-stage aerobic/anaerobic denitrifying horizontal bioreactor designed for
      treating ammonium and H(2)S simultaneously.
AB  - A two-stage bioreactor was operated for a period of 140 days in order to develop
      a post-treatment process based on anaerobic bioxidation of sulfite. This process
      was designed for simultaneously treating the effluent and biogas of a full-scale
      UASB reactor, containing significant concentrations of NH(4) and H(2)S,
      respectively. The system comprised of two horizontal-flow bed-packed reactors
      operated with different oxygen concentrations. Ammonium present in the effluent
      was transformed into nitrates in the first aerobic stage. The second anaerobic
      stage combined the treatment of nitrates in the liquor with the hydrogen sulfide
      present in the UASB-reactor biogas. Nitrates were consumed with a significant
      production of sulfate, resulting in a nitrate removal rate of 0.43 kgNm(3)day(-1)
      and >=92 % efficiency. Such a removal rate is comparable to those achieved by
      heterotrophic denitrifying systems. Polymeric forms of sulfur were not detected
      (elementary sulfur); sulfate was the main product of the sulfide-based
      denitrifying process. S-sulfate was produced at a rate of about 0.35 kgm(3)day(
      1). Sulfur inputs as S-H(2)S were estimated at about 0.75 kgm(3)day(-1) and
      Chemical Oxygen Demand (COD) removal rates did not vary significantly during the
      process. DGGE profiling and 16S rRNA identified Halothiobacillus-like species as
      the key microorganism supporting this process; such a strain has not yet been
      previously associated with such bioengineered systems.

PMID- 22956303
TI  - A randomized effectiveness trial of brief parent training in primary care
      settings.
AB  - Brief Parent Training (BPT) is a short-term intervention (3-5 sessions) delivered
      by regular staff in municipal child and family services. BPT is based on social
      interaction learning theory and Parent Management Training, the Oregon model
      (PMTO) and promotes parenting skills in families with children who either are at
      an early stage of problem behavior development or have developed conduct
      problems. This study examined the effectiveness of BPT compared to regular
      services in primary care settings at post assessment. Participants were 216
      children (3-12 years) and their parents who were randomly assigned to BPT or the
      comparison group. Data were collected from parents and teachers. Significant
      intervention effects emerged for caregiver assessments of parenting practices,
      child conduct problems, and social competence. The results suggested that BPT had
      beneficial effects for families, although the generalization of the effects to
      school was limited.

PMID- 22956304
TI  - Marriage and divorce among young adult cancer survivors.
AB  - PURPOSE: We examined marital outcomes among cancer survivors diagnosed during
      early adulthood from the 2009 Behavioral Risk Factor Surveillance System dataset.
      METHODS: Eligible participants were ages 20-39 years. Of the 74,433 eligible, N =
      1,198 self-reported a cancer diagnosis between the ages of 18 and 37, were >=2
      years past diagnosis, and did not have non-melanoma skin cancer. The remaining N
      = 67,063 were controls. Using generalized linear models adjusted for age, gender,
      race, and education, we generated relative risks (RR) and 95 % confidence
      intervals (95 % CI) to examine survivor status on indicators of ever married,
      currently married, and divorced/separated. RESULTS: Survivors were slightly older
      than controls [33.0 (SD = 3.8) vs. 30.0 (SD = 4.0); p < 0.001]. Average time
      since diagnosis was 7.4 years. Most common diagnoses were cervical (females; 45
      %) and non-Hodgkin lymphoma (males; 20 %). Survivors were less likely to be
      currently married than controls (58 % vs. 64 %; RR = 0.92, 95 % CI 0.85-0.99).
      Among ever married participants, survivors were at an increased risk of
      divorce/separation than controls (18 % vs. 10 %; RR = 1.77, 95 % CI 1.43-2.19).
      Divorce/separation risk persisted for female survivors (RR 1.83, 95 % CI 1.49
      2.25), survivors ages 20-29 (RR 2.57, 95 % CI 1.53-4.34), and survivors ages 30
      39 (RR 1.62, 95 % CI 1.29-2.04). CONCLUSIONS: The emotional and financial burdens
      of cancer may lead to marital stress for younger cancer survivors. IMPLICATIONS
      FOR CANCER SURVIVORS: Young survivors may face a higher risk of divorce; support
      systems are needed to assist them in the years following diagnosis.

PMID- 22956305
TI  - Association of bone mineral density with incidental renal stone in long-term
      survivors of childhood acute lymphoblastic leukemia.
AB  - PURPOSE: Our objective was to evaluate the association between low bone mineral
      density (BMD) and incidental renal stones among long-term survivors of childhood
      acute lymphoblastic leukemia (ALL). METHODS: Adult participants who were 10+
      years from their childhood ALL diagnosis and members of the St. Jude Lifetime
      Cohort study were recruited between December 2007 and March 2011. During their
      risk-based medical evaluations, they underwent quantitative computed tomography
      (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists'
      review of axial QCT source images. Demographic and dietary information were
      abstracted from health surveys and the Block Food Frequency questionnaire,
      respectively. The multivariable logistic regression model was used for analysis.
      RESULTS: At a median of 26.1 years from diagnosis, BMD Z scores were <=-2 in 34
      of 662 (5.2 %) and renal stones detected in 73 of 662 (11 %) participants.
      Adjusted for age, renal radiation, dietary vitamin D, gender, and body mass
      index, when compared to those with BMD Z scores >=0, the risk of renal stones was
      increased among those with BMD Z scores <=-2 (odds ratio [OR], 2.92; 95 %
      confidence interval [CI] 1.14-7.48). Risk of renal stones significantly increased
      for older age (45-54 vs.18-24 years; OR, 3.70; 95 % CI 1.11-12.35) whereas the
      risk was higher but nonsignificant for >141.5 IU (sample median) daily intake of
      vitamin D (OR, 1.64; 95 % CI 0.98-2.75). CONCLUSIONS AND IMPLICATIONS FOR CANCER
      SURVIVORS: Older ALL survivors with BMD Z scores <=-2 are at risk for renal
      stones and should be counseled so that appropriate follow-up care can be provided
      for those among whom renal stones are detected.

PMID- 22956306
TI  - Epitestosterone and testosterone have similar nonclassical actions on membrane of
      Sertoli cells in whole seminiferous tubules.
AB  - Epitestosterone is the 17alpha-epimer of testosterone. This steroid possesses
      antiandrogenic activities. The mechanism of action of epitestosterone has not
      been elucidated. The aim of this study was to investigate the nonclassical effect
      of epitestosterone on the membrane of Sertoli cells in proliferative phase (rats
      aged 15 days) and in nonproliferative phase (rats aged 21 and 35 days). The
      membrane potential of Sertoli cells was recorded using a standard single
      microelectrode technique. Epitestosterone (0.5, 1, and 2 MUM) or testosterone (1
      MUM) was administered alone and after infusion with flutamide (1 MUM), verapamil
      (100 MUM), or U-73122 (2 MUM). The testes of rats aged 12-15 days were
      preincubated with 45Ca2+ with or without flutamide (1 MUM) and incubated with
      epitestosterone (1 MUM) or testosterone (1 MUM). Epitestosterone and testosterone
      produced a depolarization in the membrane potential and increased the membrane
      input resistance on Sertoli cells from rats of all 3 ages. The effect of
      epitestosterone did not change after perfusion with flutamide. Epitestosterone
      increased 45Ca2+ uptake within 5 min and this effect was not inhibited by
      flutamide. The absence of an effect by flutamide suggests that epitestosterone
      acts independently of the intracellular androgen receptor. The depolarizing
      effect was inhibited by verapamil, a voltage-dependent calcium channel blocker,
      and by U-73122, a phospholipase C inhibitor. These results indicate that
      epitestosterone acts on the membrane via a nonclassical signaling pathway; the
      effect was similar to the testosterone action on membrane of Sertoli cells in
      whole seminiferous tubules from rat testes.

PMID- 22956307
TI  - Role of TNF-alpha in renal damage in mice showing hepatic steatosis induced by
      high fat diet.
AB  - The present study was designed to investigate the role of TNF-alpha in renal
      damage observed in mice with hepatic steatosis. We induced hepatic steatosis in
      mice using high fat diet and treated mice with ectanercept at the dose sufficient
      to block TNF-alpha receptors or vehicle for 1 month. Plasma TNF-alpha, total
      cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), and HDL-cholesterol
      (HDL-C) were determined at the end of this treatment. Renal damage was identified
      by histologic observation and the higher of serum blood urea nitrogen (BUN) and
      creatinine. Also, changes of PPAR-delta in kidney and renal mesangial cell (RMC)
      were analyzed using Western blot. Plasma TNF-alpha was markedly raised in mice
      showing hepatic steatosis. However, the levels of blood lipids (TC, TG, HDL-C,
      and LDL-C) and TNF-alpha were not modified by the treatment of etanercept
      although the hepatic steatosis has been improved. Etanercept shows renal
      protection from histological identification and recovery of serum BUN and
      creatinine levels. Moreover, restoration of PPAR-delta expression by etanercept
      was observed in mice kidney. Direct effect of TNF-alpha on PPAR-delta expression
      was also characterized in RMC cell. We suggest that renal damage in mice with
      hepatic steatosis is mainly induced by increase of TNF-alpha through the decrease
      of renal PPAR-delta. Etanercept could block TNF-alpha receptors to restore PPAR
      delta and improve renal function in mice with hepatic steatosis.

PMID- 22956308
TI  - Effects of adrenomedullin on tumour necrosis factor alpha, interleukins,
      endothelin-1, leptin, and adiponectin in the epididymal fat and soleus muscle of
      the rat.
AB  - Adrenomedullin (ADM) is a peptide hormone, which participates in the development
      of metabolic syndrome. In this study, we have investigated the interaction of ADM
      and cytokines, endothelin-1 (EDN-1) and adipokines in the epididymal fat and the
      soleus muscle. Epididymal fat and soleus muscles from adult male Sprague-Dawley
      rat were incubated with ADM at concentration of 100 nM for the study of the gene
      expression and secretion of tumour necrosis factor (TNF-alpha), EDN-1, leptin,
      adiponectin, interleukin 1beta (IL-1beta), and IL-6. The effects of TNF-alpha and
      EDN-1 on ADM gene expression and secretion were also investigated. The results
      showed that ADM decreased the gene expression and protein secretion of TNF-alpha
      in both the epididymal fat and the soleus muscle and decreased IL-1beta gene
      expression and secretion in the soleus muscle. It also decreased endothelin gene
      expression and adiponectin gene expression and release and increased IL-6 and
      leptin gene expression and secretion in the epididymal fat. These effects were
      effectively blocked by the calcitonin gene-related peptide (CGRP) receptor
      antagonist, hCGRP8-37, but not by the ADM receptor antagonist, hADM22-52. The
      reduction of inflammatory cytokines and EDN-1 may help to decrease insulin
      resistance and increase glucose uptake. As TNF-alpha also increases ADM levels in
      the epididymal fat and the soleus muscle and EDN-1 also increases ADM levels in
      the epididymal fat, they may form a feedback loop with ADM in these tissues. The
      increase in leptin and the decrease in adiponectin by ADM in the epididymal fat
      may have opposite effects on metabolism.

PMID- 22956310
TI  - Oxidative degradation of bis(2,4,4-trimethylpentyl)dithiophosphinic acid in
      nitric acid studied by electrospray ionization mass spectrometry.
AB  - RATIONALE: The selective separation of the minor actinides (Am, Cm) from the
      lanthanides is a topic of ongoing nuclear fuel cycle research, and
      dithiophosphinic acids are candidate ligands in these processes. Ligand
      instability has been noted under radiolytic and harsh acid conditions but
      explicit degradation pathways for ligands such as bis(2,4,4-trimethylpentyl)
      dithiophosphinic acid (CyxH), the major compound in the commercial product Cyanex
      301, have been elusive. METHODS: Organic solutions of CyxH were contacted with
      aqueous solutions of HNO(3), and their degradation was studied by analyzing
      samples from these experiments by direct infusion electrospray ionization mass
      spectrometry. Ions were identified using accurate mass measurement and collision
      induced dissociation. RESULTS: The positive ion spectra contained cationized CyxH
      cluster ions, and oxidatively coupled species (designated Cyx(2)) cationized by
      either H or Na. The Cyx(2)-derived ions increased with acid contact time. The
      negative ion spectra consisted almost entirely of the CyxH conjugate base. The
      negative ion spectra of the HNO(3)-contacted samples also contained conjugate
      bases corresponding to the dioxo and perthio derivatives of CyxH. CONCLUSIONS:
      CyxH is oxidized by acid contact to form the coupled species Cyx(2), and the
      dioxo species arise from subsequent oxidation of Cyx(2). Oxidative coupling
      increases with contact time, and with higher HNO(3) concentrations. The direct
      infusion measurements provided a simple approach for assessing degradation
      pathways and kinetics.

PMID- 22956311
TI  - Effect of cluster expansion on photoionization of iron pentacarbonyl doped inert
      gas clusters under gigawatt intensity laser irradiation.
AB  - RATIONALE: The aim of the investigation was to understand the variation in
      ionization dynamics of inert gas clusters upon doping with species with lower
      ionization energy than the inert gas constituent. It was postulated that the use
      of dopant species having lower ionization energy would lead to facile ionization
      of doped inert gas clusters, resulting in enhancement of the charge state of
      atomic ions compared with those obtained for pure inert gas clusters. METHODS:
      Inert gas clusters (Ar(n), Kr(n) or Xe(n)) doped with iron pentacarbonyl were
      generated by supersonic expansion and subjected to gigawatt intensity laser
      pulses (266, 355, 532 and 1064 nm wavelengths) obtained from a nanosecond Nd:YAG
      laser. The ions generated upon laser-cluster interaction were characterized using
      a time-of-flight mass spectrometer. RESULTS: Upon interaction of the laser with
      the doped inert gas clusters, the charge states of the atomic ions were found to
      increase with the laser wavelength. However, the highest observed charge states
      were found to be lower for doped inert gas clusters than for pure inert gas
      clusters, at all laser wavelengths. CONCLUSIONS: Wavelength-dependent generation
      of multiply charged atomic ions has been explained based on the three stage
      model, i.e. multiphoton ionization ignited-inverse bremsstrahlung heating, and
      electron ionization. This model explains enhancement in the charge state of
      atomic ions with increasing wavelength based on inverse bremsstrahlung heating of
      the inner ionized electron, which is a more efficient process at longer
      wavelengths. Inefficient coupling of laser energy in the case of doped inert gas
      clusters compared with pure inert gas clusters has been rationalized on the basis
      of accelerated disintegration of the cluster due to facile initial ionization of
      dopant molecules having low ionization energy. The results suggest that a longer
      laser wavelength and a slower rate of cluster expansion facilitate the efficient
      transfer of optical energy into cluster systems.

PMID- 22956309
TI  - Gastric dysmotility and low serum vitamin D levels in patients with
      gastroparesis.
AB  - Nutritional abnormalities are common in patients with gastroparesis (Gp), a
      disorder that may affect gastric motility and may delay emptying. The aim of this
      work was to identify relationships between serum nutrition markers including 25
      OH vitamin D and gastric motility measures in Gp patients. We enrolled 59
      consecutive gastric motility clinic patients (48 females, 11 males; mean age 44
      years; 42 idiopathic; 17 diabetes mellitus) with Gp symptoms. The 25-OH vitamin D
      levels, for most patients slightly above the lower limit of normal (96.98 nmol/l
      +/- 60.99), were lowest in diabetic range (DM) (75.68 nmol/l +/- 34.22) vs.
      idiopathic (ID) (105.03 nmol/l +/- 67.08) gastroparesis patients. First hour GET:
      one unit increase in 25-OH vitamin D level was associated 0.11% improvement (95%
      CI -0.22, 0.01 p=0.056) in gastric motility in all patients; this association,
      although marked in ID Gp patients, (-0.13, CI -0.25, -0.01 p=0.034), was not seen
      in DM Gp, (0.2, CI -0.45, 0.87, p=0.525). Fourth hour GET: Every unit increase of
      25-OH vitamin D was associated with significant improvement in all patients, (
      0.11% CI -0.23, 0.01, p=0.053), and some weak improvement in ID group, (0.11% 
      0.24, 0.01, p=0.076) and absent in patients with DM (0.03, CI -0.66, 0.72,
      p=0.932). It is concluded that 25-OH vitamin D levels may influence gastric
      emptying. Underlying mechanisms for this observation might include the impact of
      25-OH vitamin D on the health of the enteric nervous system. 25-OH vitamin D
      contributions to enteric nerve functions should be explored, particularly where
      autonomic nervous system comorbidities exist.

PMID- 22956312
TI  - Buffer gas modifiers effect resolution in ion mobility spectrometry through
      selective ion-molecule clustering reactions.
AB  - RATIONALE: When polar molecules (modifiers) are introduced into the buffer gas of
      an ion mobility spectrometer, most ion mobilities decrease due to the formation
      of ion-modifier clusters. METHODS: We used ethyl lactate, nitrobenzene, 2
      butanol, and tetrahydrofuran-2-carbonitrile as buffer gas modifiers and
      electrospray ionization ion mobility spectrometry (IMS) coupled to quadrupole
      mass spectrometry. Ethyl lactate, nitrobenzene, and tetrahydrofuran-2
      carbonitrile had not been tested as buffer gas modifiers and 2-butanol had not
      been used with basic amino acids. RESULTS: The ion mobilities of several diamines
      (arginine, histidine, lysine, and atenolol) were not affected or only slightly
      reduced when these modifiers were introduced into the buffer gas (3.4% average
      reduction in an analyte's mobility for the three modifiers). Intramolecular
      bridges caused limited change in the ion mobilities of diamines when modifiers
      were added to the buffer gas; these bridges hindered the attachment of modifier
      molecules to the positive charge of ions and delocalized the charge, which
      deterred clustering. There was also a tendency towards large changes in ion
      mobility when the mass of the analyte decreased; ethanolamine, the smallest
      compound tested, had the largest reduction in ion mobility with the introduction
      of modifiers into the buffer gas (61%). These differences in mobilities, together
      with the lack of shift in bridge-forming ions, were used to separate ions that
      overlapped in IMS, such as isoleucine and lysine, and arginine and phenylalanine,
      and made possible the prediction of separation or not of overlapping ions.
      CONCLUSIONS: The introduction of modifiers into the buffer gas in IMS can
      selectively alter the mobilities of analytes to aid in compound identification
      and/or enable the separation of overlapping analyte peaks.

PMID- 22956313
TI  - High-resolution secondary ion mass spectrometry depth profiling of nanolayers.
AB  - RATIONALE: Although the fundamental physical limits for depth resolution of
      secondary ion mass spectrometry are well understood in theory, the experimental
      work to achieve and demonstrate them is still ongoing. We report results of high
      resolution TOF SIMS (time-of-flight secondary ion mass spectrometry) depth
      profiling experiments on a nanolayered structure, a stack of 16 alternating MgO
      and ZnO ~5.5 nm layers grown on a Si substrate by atomic layer deposition.
      METHODS: The measurements were performed using a newly developed approach
      implementing a low-energy direct current normally incident Ar(+) ion beam for ion
      milling (250 eV and 500 eV energy), in combination with a pulsed 5 keV Ar(+) ion
      beam at 60 degrees  incidence for TOF SIMS analysis. By this optimized
      arrangement, a noticeably improved version of the dual-beam (DB) approach to TOF
      SIMS depth profiling is introduced, which can be dubbed gentleDB. RESULTS: The
      mixing-roughness-information model was applied to detailed analysis of
      experimental results. It revealed that the gentleDB approach allows ultimate
      depth resolution by confining the ion beam mixing length to about two monolayers.
      This corresponds to the escape depth of secondary ions, the fundamental depth
      resolution limitation in SIMS. Other parameters deduced from the measured depth
      profiles indicated that a single layer thickness is equal to 6 nm so that the
      'flat' layer thickness d is 3 nm and the interfacial roughness sigma is 1.5 nm,
      thus yielding d + 2sigma = 6 nm. CONCLUSIONS: We have demonstrated that gentleDB
      TOF SIMS depth profiling with noble gas ion beams is capable of revealing the
      structural features of a stack of nanolayers, resolving its original surface and
      estimating the roughness of interlayer interfaces, information which is difficult
      to obtain by traditional approaches.

PMID- 22956314
TI  - Broadband non-selective excitation of plutonium isotopes for isotope ratio
      measurements in resonance ionization mass spectrometry: a theoretical study.
AB  - RATIONALE: Making isotope ratio measurements with minimum isotope bias has always
      been a challenging task to mass spectrometrists, especially for the specific case
      of plutonium, owing to the strategic importance of the element. In order to use
      resonance ionization mass spectrometry (RIMS) as a tool for isotope ratio
      measurements, optimization of the various laser parameters and other atomic and
      system parameters is critical to minimize isotopic biases. METHODS: Broadband
      simultaneous non-selective excitation of the isotopes of plutonium in the triple
      resonance excitation scheme with lambda(1) = 420.77 nm, lambda(2) = 847.28 nm,
      and lambda(3) = 767.53 nm based on density matrix formalism has been
      theoretically computed for the determination of isotope ratios. The effects of
      the various laser parameters and other factors such as the atomization
      temperature and the dimensions of the atomic beam on the estimation of isotope
      ratios were studied. The effects of Doppler broadening, and time-dependent
      excitation parameters such as Rabi frequencies, ionization rate and the effect of
      non-Lorenztian lineshape have all been incorporated. RESULTS: The average laser
      powers and bandwidths for the three-excitation steps were evaluated for non
      selective excitation. The laser intensity required to saturate the three
      excitation steps were studied. The two-dimensional lineshape contour and its
      features were investigated, while the reversal of peak asymmetry of two-step and
      two-photon excitation peaks under these conditions is discussed. Optimized powers
      for the non-selective ionization of the three transitions were calculated as 545
      mW, 150 mW and 545 mW and the laser bandwidth for all the three steps was ~20
      GHz. CONCLUSIONS: The isotopic bias between the resonant and off-resonant isotope
      under the optimized conditions was no more than 9%, which is better than an
      earlier reported value. These optimized laser power and bandwidth conditions are
      better than in the earlier experimental work since these comprehensive
      calculations yield simultaneous and much more accurate isotope ratios than those
      in the sequential and less accurate determination reported earlier. Application
      of these theoretical calculations to minimize the isotopic biases under these
      conditions for the rapid, efficient and accurate isotope ratio measurements using
      RIMS has been outlined.

PMID- 22956315
TI  - Assessing the rate and timing of leaf wax regeneration in Fraxinus americana
      using stable hydrogen isotope labeling.
AB  - RATIONALE: Understanding leaf wax regeneration and recycling is crucial for plant
      physiology and paleoclimate studies. However, our recent isotope labeling
      experiments on a grass species (Phleum pratense) yielded different conclusions
      from published data on a tree species (Populus trichocarpa), with the former
      showing rapid regeneration and the latter little regeneration in mature leaves.
      It is therefore important to determine if the discrepancies in published results
      were due to differing dynamics of leaf wax regeneration and/or caveats in
      experimental methods. METHODS: Leaves from a native New England tree species
      (Fraxinus americana) were collected at 1 to 3 h intervals over a 2-day
      experimental period, and, subsequently, the leaf wax delta(2) H isotopic ratios
      were measured using gas chromatography/isotope ratio mass spectrometry. RESULTS:
      It was necessary to irrigate the tree using water with significantly higher
      delta(2) H values than that used for the grass in order to obtain readily
      measurable isotopic responses over diurnal cycles. In addition, diurnal leaf wax
      regeneration in Fraxinus americana was delayed by 1-4 h relative to Phleum
      pratense, suggesting that the latter produced leaf waxes from more recently
      photosynthesized substrates. CONCLUSIONS: The isotopic inertia in Fraxinus
      americana was due to lower leaf wax regeneration rates than in Phleum pratense by
      one to two orders of magnitude. The difference in the timing of leaf wax
      biosynthesis might partially account for the observed leaf wax hydrogen isotopic
      difference between trees and grasses.

PMID- 22956316
TI  - Characterisation of (E)-2-styrylchromones by electrospray ionisation mass
      spectrometry: singular gas-phase formation of benzoxanthenones.
AB  - RATIONALE: The electrospray ionisation (ESI) mass spectra (ESI-MS(n) , n = 2 and
      3) of six (E)-2-styrylchromones containing electron-donating and electron
      withdrawing groups were studied for the first time. The potential application of
      these compounds as drug candidates brings a need for the development of an
      analytical method to ensure a detailed knowledge of their structures. METHODS:
      ESI-MS, CID-MS(2) and MS(3) spectra of all the studied compounds were acquired
      using a LXQ linear ion trap mass spectrometer with an electrospray source,
      operating in the positive ion mode. ESI conditions were: nitrogen 8.00 sheath gas
      flow rate (arb), spray voltage 5 kV, heated capillary temperature 275  degrees C,
      capillary voltage 10.99 V and tube lens voltage 75.01 V. CID-MS(2) and MS(3)
      experiments were performed on mass-selected precursor ions using standard
      isolation and excitation procedures (activation q value of 0.25, activation time
      of 30 ms). RESULTS: A comparable pattern of product ions was observed for all the
      studied compounds. Only the product ion ((1,2)(3,4)) A(+) is common to all the
      studied compounds. Common to compounds 1 (R(2) = H), 1a (R(2) = OMe) and 1c (R(2)
      = Cl) are the product ions formed by loss of H(2)O, CO, C(6)H(5)OH, and the
      product ions ((1,2)(2,3))B(+) and ((1,2)(3,4))B(+). Among all compounds, 2-SC 1b
      (R(2) = NO(2)) shows an obvious differentiation showing the lowest number of
      product ions under CID-MS(2) conditions. CONCLUSIONS: The analysed compounds
      revealed a comparable pattern of product ions formed for each compound only
      different in what concerns the relative abundance of these formed product ions. A
      rather interesting and unexpected loss of 2 Da was observed for some compounds.
      The structure of a benzoxanthenone was proposed for this product ion based on
      evidence obtained by synthesised benzoxanthenone as a model compound.

PMID- 22956317
TI  - Surfactant self-assembling in the gas phase: bis(2-ethylhexyl)-sulfosuccinate
      divalent metal ion anionic aggregates.
AB  - RATIONALE: Investigation of fundamental aspects driving surfactant self
      assembling and of the capability of including guest molecules or ions in their
      micellar aggregates is an exciting research field for theoretical and
      technological reasons. In this light, assembling and chelating properties of
      sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) towards divalent metal ion
      chlorides have been investigated in the gas phase by electrospray ionization mass
      spectrometry in negative ion mode, tandem mass spectrometry and energy-resolved
      mass spectrometry. METHODS: Water/methanol solutions of AOTNa and chloride salts
      of nickel, magnesium, calcium and manganese, with different AOTNa/metal salt
      ratios, were infused into the electrospray source of a LCQ DECA ion trap mass
      spectrometer, operating in negative ion mode, at a flow rate of 5 MUL/min. Low
      energy collision-induced dissociations were carried out by using helium with
      collision energy in the range 1-5 eV. RESULTS: A variety of negatively singly
      charged monometallated and mixed metal aggregates have been observed, some of
      which were able to incorporate the metal counter ion of the inorganic salt used.
      The stability of these aggregates was evaluated by energy-resolved mass
      spectrometry which showed, for the anions [AOTM(II)Cl(2)](-), a stability order
      Ca > Mn > Mg > Ni. Their decomposition pathways show the unusual formation of the
      radical anions [C(4)HO(6)SM(II)Cl](-*). CONCLUSIONS: This study shed some light
      on the assembling and chelating properties of AOT(-) towards divalent metal ions
      to form negatively charged assemblies, some of them incorporating the metal
      counter ion of the inorganic salt used. Differently from what was observed with
      positively charged AOT-M(II) aggregates, solvated species were not detectable. An
      exception to the even-electron rule was observed in the decomposition pathway of
      [AOTM(II)Cl(2)](-).

PMID- 22956318
TI  - Quantification of cardiolipin molecular species in Escherichia coli lipid
      extracts using liquid chromatography/electrospray ionization mass spectrometry.
AB  - RATIONALE: Cardiolipin (CL), a glycerophospholipid containing four acyl chains,
      is found in most organisms including Gram-negative bacteria such as Escherichia
      coli. While CL composes only a fraction of the total glycerophospholipids, the
      four acyl chains lead to a large number of possible molecular species as defined
      by the total number of carbons and unsaturations in the acyl chains.
      Understanding the molecular composition of CL, and how it changes under different
      growth conditions, will aid in understanding the complex role of CL in E. coli.
      METHODS: Normal-phase liquid chromatography/electrospray ionization mass
      spectrometry was used to quantify the CL molecular species (as defined by the
      total number of carbons:unsaturations in the acyl chains) in lipid extracts
      prepared from E. coli grown at 15  degrees C, 30  degrees C, 37  degrees C and 42
      degrees C. RESULTS: Fifty-six different CL species were identified as [M-2H](2-)
      ions in E. coli lipid extracts ranging from 60:0 to 72:4. CL species with an
      increased total number of unsaturations were more abundant in lipid extracts
      prepared from cells grown at 15  degrees C as compared to higher temperatures.
      CONCLUSIONS: This work characterizes the CL composition of E. coli cells grown at
      various temperatures. By quantifying CL species at a molecular level we have
      illuminated the molecular complexity of the CL in this relatively simple model
      organism. This data will be useful for understanding CL function in E. coli and
      other organisms.

PMID- 22956320
TI  - Electrospray ionization mass spectrometric investigations of the complexation
      behavior of macrocyclic thiacrown ethers with bivalent transitional metals (Cu,
      Co, Ni and Zn).
AB  - RATIONALE: Heavy metals are both a problem for the environment and an important
      resource for industry. Their selective extraction by means of organic ligands
      therefore is an attractive topic. The coordination of three thiacrown ethers to
      late 3d-metal ions was investigated by a combination of electrospray ionization
      mass spectrometry (ESI-MS) and electron paramagnetic resonance (EPR). METHODS:
      The mass spectrometric experiments were carried out in an ion trap mass
      spectrometer with an ESI source. Absolute binding constants were estimated by
      comparison with data for 18-crown-6/Na(+). EPR spectroscopy was used as a
      complementary method for investigating the Cu(I) /Cu(II) redox couple. RESULTS:
      The study found that thiacrown ethers preferentially bind traces of copper even
      at an excess of other metal ions (Co(II), Ni(II), and Zn(II)). The absolute
      association constants of the Cu(I) complexes were about 10(8) M(-1), and about
      two orders of magnitude lower for the other 3d-metal cations. The EPR spectra
      demonstrated that the reduction from Cu(II) to Cu(I) upon formation of the
      [(thiacrown)Cu](+) species takes place in solution. CONCLUSIONS: ESI-MS
      demonstrated that the three thiacrown ligands examined had high binding constants
      as well as good selectivities for copper(I) at low concentrations, and in the
      presence of other metal ions. By a combination of ESI-MS and EPR spectrometry it
      was shown that the reduction from Cu(II) to Cu(I) occurred in solution.

PMID- 22956319
TI  - Fragmentation trees for the structural characterisation of metabolites.
AB  - Metabolite identification plays a crucial role in the interpretation of
      metabolomics research results. Due to its sensitivity and widespread
      implementation, a favourite analytical method used in metabolomics is
      electrospray mass spectrometry. In this paper, we demonstrate our results in
      attempting to incorporate the potentials of multistage mass spectrometry into the
      metabolite identification routine. New software tools were developed and
      implemented which facilitate the analysis of multistage mass spectra and allow
      for efficient removal of spectral artefacts. The pre-processed fragmentation
      patterns are saved as fragmentation trees. Fragmentation trees are characteristic
      of molecular structure. We demonstrate the reproducibility and robustness of the
      acquisition of such trees on a model compound. The specificity of fragmentation
      trees allows for distinguishing structural isomers, as shown on a pair of
      isomeric prostaglandins. This approach to the analysis of the multistage mass
      spectral characterisation of compounds is an important step towards formulating a
      generic metabolite identification method.

PMID- 22956321
TI  - Extending the known range of glycerol ether lipids in the environment: structural
      assignments based on tandem mass spectral fragmentation patterns.
AB  - RATIONALE: Glycerol-based alkyl ether lipids are ubiquitous components in marine
      sediments. In order to explore their structural diversity and biological sources,
      marine sediment samples from diverse environments were analyzed and the mass
      spectra of widely distributed, novel glycerol di- and tetraethers were examined
      systematically. METHODS: Lipid extracts of twelve globally distributed marine
      subsurface sediments were analyzed by atmospheric pressure chemical ionization
      mass spectrometry (APCI-MS). Tandem mass (MS/MS) spectra of compounds were
      obtained with a quadrupole time-of-flight (qTOF) mass spectrometer. RESULTS: In
      addition to the well-established isoprenoidal glycerol dialkyl glycerol
      tetraether (isoprenoidal GDGT) and branched GDGT, suites of novel lipids were
      detected in all studied samples. These lipids include the following classes of
      tentatively identified compounds: isoprenoidal glycerol dialkanol diether
      (isoprenoidal GDD), hydroxylated isoprenoidal GDGT (OH-GDGT), hybrid
      isoprenoidal/branched GDGT (IB-GDGT), hydroxylated isoprenoidal GDD (OH-GDD),
      overly branched GDGT (OB-GDGT), sparsely branched GDGT (SB-GDGT) and an abundant
      H-shaped GDGT with the [M+H](+) ion of m/z 1020 (H-1020). CONCLUSIONS:
      Characteristic MS/MS fragmentation patterns provided mass spectral 'fingerprints'
      for the recognition of diverse and prominent glycerol ether lipids. The
      ubiquitous distribution and substantial abundance of these glycerol ethers, as
      well as their structural variability, suggest a significant ecological role of
      their source organisms in various marine environments.

PMID- 22956322
TI  - Correlation of Ecom50 values between mass spectrometers: effect of collision cell
      radiofrequency voltage on calculated survival yield.
AB  - RATIONALE: The determination of the center-of-mass energy at which 50% of a
      precursor ion decomposes (Ecom(50)) during collision-induced dissociation (CID)
      is dependent on the chemical structure of the ion as well as the physical and
      electrical characteristics of the collision cell. The current study was designed
      to identify variables influencing Ecom(50) values measured on four different mass
      spectrometers. METHODS: Fifteen test compounds were protonated using + ve
      electrospray ionization and the resulting ions were fragmented across a range of
      collision energies by CID. Survival yield versus collision energy curves were
      then used to calculate Ecom(50) values for each of these [M+H](+) ions on four
      different mass spectrometers. In addition, the relative recovery of the [M+H](+)
      ions of eight compounds ranging in molecular weight from 46 to 854 Da were
      determined at collision cell radiofrequency (RF) voltages ranging from 0 to 600
      V. RESULTS: Ecom(50) values determined on the four instruments were highly
      correlated (r(2) values ranged from 0.953 to 0.992). Although these overall
      correlations were high, we found different maximum ion recoveries depending on
      collision cell RF voltage. High-mass ions had greater recovery at higher
      collision cell RF voltages, whereas low-mass ions had greater recovery at lower
      collision cell RF voltages as well as a broader range of ion recoveries.
      CONCLUSIONS: Ecom(50) values measured on four different instruments correlated
      surprisingly well given the differences in electrical and physical
      characteristics of the collision cells. However, our results suggest caution when
      comparing Ecom(50) values or CID spectra between instruments without correcting
      for the effects of RF voltage on ion transfer efficiency.

PMID- 22956323
TI  - On-plate deposition of oxidized proteins to facilitate protein footprinting
      studies by radical probe mass spectrometry.
AB  - The on-plate deposition of oxidized proteins is described to advance footprinting
      applications by radical probe mass spectrometry (RP-MS). An electrospray
      ionization (ESI) needle assembly mounted vertically over a 384-target matrix
      assisted laser desorption/ionization (MALDI) plate enabled the limited oxidation
      of proteins as they were released in the charged droplets ahead of their
      deposition on the plate. This method combined with on-plate proteolytic digestion
      protocols expedites the analysis of proteins oxidized by RP-MS, and avoids the
      need to collect and reconstitute samples prior to analysis by MALDI mass
      spectrometry. Oxidation of peptides from solutions in water as well as an
      ammonium bicarbonate solution was investigated to test the optimal conditions
      required for on-plate oxidation of proteins. These comprised of peptides with a
      wide range of reactive amino acids including Phe, Tyr, Pro, His, Leu, Met and Lys
      that were previously shown to oxidize in both electrospray discharge and
      synchrotron radiolysis based footprinting experiments. The on-plate deposition of
      lysozyme oxidized at electrospray needle voltages of 6 and 9 kV were carried out
      to demonstrate conditions suitable for footprinting experiments as well as those
      that induce the onset of protein damage.

PMID- 22956324
TI  - Site-specific deamidation of glutamine: a new marker of bone collagen
      deterioration.
AB  - RATIONALE: Non-enzymatic deamidation accumulates in aging tissues in vivo and has
      been proposed to be potentially useful as a molecular clock. The process
      continues post mortem, and here we explore the increase in levels of deamidation
      in archaeological collagen, as measured during Zooarchaeology by Mass
      Spectrometry (ZooMS) analysis. METHODS: With the high sensitivity of current
      generation mass spectrometers, ZooMS provides a non-destructive and highly cost
      effective method to characterise collagen peptides. Deamidation can be detected
      by mass spectrometry as a +0.984 Da mass shift; therefore, aside from its
      original purpose, peptide mass-fingerprinting for bone identification, ZooMS
      concurrently yields a 'thermal indicator' of the samples. RESULTS: By analysis of
      conventional ZooMS spectra, we determined the deamidation rate for glutamine
      residues in 911 bone collagen samples from 50 sites, with ages varying from
      medieval to Palaeolithic. The degree of deamidation was compared to diagenetic
      parameters and nearby sequence properties. CONCLUSIONS: The extent of deamidation
      was found to be influenced more by burial conditions and thermal age than, for
      example, chronological age, the extent of bioerosion or crystallinity. The method
      lends itself mostly to screening heterogenic deposits of bone to identify
      outliers.

PMID- 22956325
TI  - Practical considerations in the determination of compound-specific amino acid
      delta15N values in animal and plant tissues by gas chromatography-combustion
      isotope ratio mass spectrometry, following derivatisation to their N
      acetylisopropyl esters.
AB  - RATIONALE: Stable nitrogen isotope (delta(15)N) values of bone collagen are
      routinely used to inform interpretations of diet and trophic positions within
      contemporary and ancient ecosystems, yet the underlying physiological and
      biochemical factors which contribute to the bulk collagen delta(15)N value remain
      little understood. Determination of individual amino acid (AA) delta(15)N values
      in animal and plant proteins can help to elucidate the cycling of nitrogen and
      inform predictions of palaeodiet and ecology. METHODS: In this study we present a
      methodology for the measurement of amino acid delta(15)N values using gas
      chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Amino acid
      standards of known delta(15)N values were derivatised to their N-acetylisopropyl
      (NAIP) esters and purified through Dowex ion-exchange resin to determine any
      isotopic fractionation associated with derivatisation and ion-exchange
      chromatography. The effect of starch on AA delta(15)N values was also determined
      by hydrolysing bone collagen with and without the presence of starch. RESULTS:
      The amino acids derivatised to their NAIP esters give values within +/-0.80/00 of
      their delta(15)N values measured separately by elemental analyser (EA)-IRMS, with
      a precision of better than 0.80/00. The delta(15)N values of AAs after Dowex ion
      exchange chromatography were within +/-0.90/00 of their values prior to ion
      exchange chromatography. The AA delta(15)N values of bone collagen hydrolysed
      with and without starch were within +/-0.80/00. CONCLUSIONS: Hydrolysis of lipid
      extracted plant material followed by purification of AAs using Dowex ion-exchange
      resin and derivatisation to their NAIP esters is a suitable protocol for the
      accurate determination of individual plant and animal AA delta(15)N values by GC
      C-IRMS.

PMID- 22956326
TI  - Direct analysis in real time mass spectrometry with collision-induced
      dissociation for structural analysis of synthetic cannabinoids.
AB  - RATIONALE: The emergence of numerous cannabinoid designer drugs has been tied to
      large spikes in emergency room visits and overdoses. Identifying these substances
      is difficult for the following reasons: (1) the compounds are novel, closely
      structurally related, and do not usually test positive in drug screens; (2) novel
      analogs rapidly appear on the market; (3) no standard protocols exist for their
      identification; and (4) customized and extensive sample preparation/extraction
      and analysis procedures are required to demonstrate their presence. METHODS:
      Direct analysis in real time mass spectrometry (DART-MS) employing collision
      induced dissociation (CID) provided confirmatory structural information that was
      useful in characterizing the various cannabinoid analogs, including those
      contained in mixtures. CID analysis illustrated that, although closely related
      compounds fragment in a similar fashion, their structural differences still
      resulted in multiple diagnostic peaks that provided additional confidence towards
      structural identification. RESULTS: DART-MS spectra were acquired under CID
      conditions to rapidly differentiate among five synthetic cannabinoids contained
      within 'herbal' products purchased locally in New York State (USA). The spectra
      exhibited [M+H](+) ions and product ions unique to each cannabinoid that
      corresponded to major structural features. Five different cannabinoid analogs,
      alone and as mixtures of at least two cannabinoids, were identified in six herbal
      products and differentiated by their CID product ion patterns. CONCLUSIONS:
      Illicit synthetic cannabinoid products continue to be readily available despite
      national and international restrictions. These products contain a wide range of
      active components, and, in many cases, multiple active ingredients. DART-MS
      allows rapid analyses of these synthetic cannabinoids based on the exact masses
      of their [M+H](+) ions and product ion peaks generated using CID.

PMID- 22956327
TI  - Simultaneous characterization of prenylated flavonoids and isoflavonoids in
      Psoralea corylifolia L. by liquid chromatography with diode-array detection and
      quadrupole time-of-flight mass spectrometry.
AB  - RATIONALE: Prenylated flavonoids and isoflavonoids are widely distributed
      throughout the plant kingdom, with many biological effects. Psoralea corylifolia,
      which contains many kinds of prenylated components, has been widely used as a
      medicinal plant in Asia and India for thousands of years. The goal of this study
      was to characterize the components in P. corylifolia using a liquid
      chromatography with diode-array detection and quadrupole time-of-flight mass
      spectrometry (LC-DAD/Q-TOF-MS) method, and to elucidate the fragmentation
      behavior of the different prenyl substituent groups and their appropriate
      characteristic pathways in positive ion mode. METHODS: The calculated accurate
      masses of the protonated molecules, the fragment ions, the retention behavior,
      and the data from UV spectra were used for identification of the components in P.
      corylifolia. RESULTS: A total of 45 compounds, including 43 prenylated
      components, were identified or tentatively identified in P. corylifolia.
      Different diagnostic fragment ions and neutral losses were observed in different
      prenyl substructures: neutral loss of 56 Da (C(4)H(8)) and a fragment ion at m/z
      69 (C(5)H(9)(+)) were generated by a prenyl chain; neutral losses of 42 Da
      (C(3)H(6)), 54 Da (C(4)H(6)), 15 Da (CH(3*)) and 16 Da (CH(4)) were observed in a
      ring-closed prenyl group; neutral losses of 72 Da (C(4)H(8)O), 60 Da
      (C(2)H(4)O(2)), 58 Da (C(3)H(6)O) and 18 Da (H(2)O) were detected in a 2,2
      dimethyl-3,4-dihydroxydihydropyran ring; neutral losses of 72 Da (C(4)H(8)O), 60
      Da (C(3)H(8)O) and 18 Da (H(2)O) were yielded from a 2,2-dimethyl-3
      hydroxydihydropyran ring, a 2-(1-hydroxy-1-methylethyl)dihydrofuran ring or a 1
      hydroxy-3-methylbut-3-enyl chain. CONCLUSIONS: This method can be applied for
      analysis of prenylated components in P. corylifolia and other herbal medicines.

PMID- 22956328
TI  - Distinguishing wild ruminant lipids by gas chromatography/combustion/isotope
      ratio mass spectrometry.
AB  - RATIONALE: The carbon isotopic characterisation of ruminant lipids associated
      with ceramic vessels has been crucial for elucidating the origins and changing
      nature of pastoral economies. delta(13)C values of fatty acids extracted from
      potsherds are commonly compared with those from the dairy and carcass fats of
      modern domesticated animals to determine vessel use. However, the processing of
      wild ruminant products in pottery, such as deer, is rarely considered despite the
      presence of several different species on many prehistoric sites. To address this
      issue, the carbon isotope range of fatty acids from a number of red deer (Cervus
      elaphus) tissues, a species commonly encountered in the European archaeological
      record, was investigated. METHODS: Lipids were extracted from 10 modern red deer
      tissues obtained from the Slowinski National Park (Poland). Fatty acids were
      fractionated, methylated and analysed by gas chromatography/combustion/isotope
      ratio mass spectrometry (GCCIRMS). The delta(13)C values of n-octadecanoic acid
      and n-hexadecanoic acid, and the difference between these values (Delta(13)C),
      were compared with those from previously published ruminant fats. RESULTS: Nine
      of the ten deer carcass fats measured have Delta(13)C values of less than 
      3.30/00, the threshold previously used for classifying dairy products. Despite
      considerable overlap, dairy fats from domesticated ruminants with Delta(13)C
      values less than -4.30/00 are still distinguishable. CONCLUSIONS: The finding has
      implications for evaluating pottery use and early pastoralism. The processing of
      deer tissues and our revised criteria should be considered, especially where
      there is other archaeological evidence for their consumption.

PMID- 22956329
TI  - High molecular weight non-polar hydrocarbons as pure model substances and in
      motor oil samples can be ionized without fragmentation by atmospheric pressure
      chemical ionization mass spectrometry.
AB  - RATIONALE: High molecular weight non-polar hydrocarbons are still difficult to
      detect by mass spectrometry. Although several studies have targeted this problem,
      lack of good self-ionization has limited the ability of mass spectrometry to
      examine these hydrocarbons. Failure to control ion generation in the atmospheric
      pressure chemical ionization (APCI) source hampers the detection of intact stable
      gas-phase ions of non-polar hydrocarbon in mass spectrometry. METHODS: Seventeen
      non-volatile non-polar hydrocarbons, reported to be difficult to ionize, were
      examined by an optimized APCI methodology using nitrogen as the reagent gas.
      RESULTS: All these analytes were successfully ionized as abundant and intact
      stable [M-H](+) ions without the use of any derivatization or adduct chemistry
      and without significant fragmentation. Application of the method to real-life
      hydrocarbon mixtures like light shredder waste and car motor oil was
      demonstrated. CONCLUSIONS: Despite numerous reports to the contrary, it is
      possible to ionize high molecular weight non-polar hydrocarbons by APCI, omitting
      the use of additives. This finding represents a significant step towards
      extending the applicability of mass spectrometry to non-polar hydrocarbon
      analyses in crude oil, petrochemical products, waste or food.

PMID- 22956330
TI  - Study on the noncovalent interactions of antiepileptic drugs and amyloid beta 1
      40 peptide by electrospray ionization mass spectrometry.

PMID- 22956332
TI  - Brain activity related to the ability to inhibit previous task sets: an fMRI
      study.
AB  - Switching between tasks requires individuals to inhibit mental representations of
      the previous task demands and to activate representations of the new demands. To
      date, investigators have identified only one way to measure task set inhibition
      that is, through a backward inhibition (BI) paradigm. In this paradigm,
      participants take more time to return to a task set that was recently abandoned
      (e.g., "A" in an ABA task sequence) than to a nonrecently abandoned task set
      (e.g., CBA), and investigators have demonstrated that this time cost reflects
      time needed to overcome the inhibition of the recently abandoned task set. To
      date, however, investigators have not been able to use this paradigm, or any
      other, to isolate brain activity related to task set inhibition. For example,
      contrasting the brain activity elicited by ABA and CBA trials will not isolate
      activity related to task set inhibition, because inhibition occurs during the
      initial switch away from task A (i.e., ABA). Given that there is currently no way
      to directly isolate the brain activity related to task set inhibition, we decided
      instead to examine how brain activity during task switching varies in individuals
      who are better than others at inhibiting the previous task set. We found that
      participants who were good at inhibiting previous task sets, as measured with the
      BI paradigm, exhibited more activity in the basal ganglia and supplementary motor
      area/premotor area when task switching, as measured via functional magnetic
      resonance imaging. These findings suggest that activity in these regions plays a
      role in task set inhibition.

PMID- 22956331
TI  - Distinct contributions of the caudate nucleus, rostral prefrontal cortex, and
      parietal cortex to the execution of instructed tasks.
AB  - When we behave according to rules and instructions, our brains interpret abstract
      representations of what to do and transform them into actual behavior. In order
      to investigate the neural mechanisms behind this process, we devised an fMRI
      experiment that explicitly isolated rule interpretation from rule encoding and
      execution. Our results showed that a specific network of regions (including the
      left rostral prefrontal cortex, the caudate nucleus, and the bilateral posterior
      parietal cortices) is responsible for translating rules into executable form. An
      analysis of activation patterns across conditions revealed that the posterior
      parietal cortices represent a mental template for the task to perform, that the
      inferior parietal gyrus and the caudate nucleus are responsible for instantiating
      the template in the proper context, and that the left rostral prefrontal cortex
      integrates information across complex relationships.

PMID- 22956333
TI  - Intestinal failure: a viable proposition in India.

PMID- 22956334
TI  - Promotion of Ccn2 expression and osteoblastic differentiation by actin
      polymerization, which is induced by laminar fluid flow stress.
AB  - Fluid flow stress (FSS) is a major mechanical stress that induces bone remodeling
      upon orthodontic tooth movement, whereas CCN family protein 2 (CCN2) is a potent
      regenerator of bone defects. In this study, we initially evaluated the effect of
      laminar FSS on Ccn2 expression and investigated its mechanism in osteoblastic
      MC3T3-E1 cells. The Ccn2 expression was drastically induced by uniform FSS in an
      intensity dependent manner. Of note, the observed effect was inhibited by a Rho
      kinase inhibitor Y27632. Moreover, the inhibition of actin polymerization blocked
      the FSS-induced activation of Ccn2, whereas inducing F-actin formation using
      cytochalasin D and jasplakinolide enhanced Ccn2 expression in the same cells.
      Finally, F-actin formation was found to induce osteoblastic differentiation. In
      addition, activation of cyclic AMP-dependent kinase, which inhibits Rho
      signaling, abolished the effect of FSS. Collectively, these findings indicate the
      critical role of actin polymerization and Rho signaling in CCN2 induction and
      bone remodeling provoked by FSS.

PMID- 22956335
TI  - Treatment of human sperm with serine protease during density gradient
      centrifugation.
AB  - PURPOSE: Seminal pathogens can bind specifically or non-specifically to
      spermatozoa, rendering semen decontamination procedures ineffective, whereby
      vertical or horizontal transmission of the infection could occur. Serine
      proteases have been demonstrated to effectively inactivate viruses and to break
      pathogen-sperm bonds. However, the addition of a protease to density gradient
      layers during semen processing could negatively impact on sperm parameters. This
      study investigated the effect of the addition of a recombinant, human-sequence
      protease (rhProtease) on sperm parameters during density gradient centrifugation.
      METHODS: (i) Pooled semen samples (n = 9) were split and processed by density
      gradient centrifugation, with the top density layers supplemented, or non
      supplemented with rhProtease at three different concentrations (diluted 2, 10 and
      20 times). Sperm parameters were then analysed by flow cytometry and computer
      assisted semen analyses. (ii) Semen samples (n = 5) were split and similarly
      processed using PureSperm(r) Pro, with rhProtease in the 40 % density gradient
      layer, or standard PureSperm(r) not supplemented with rhProtease (Nidacon,
      International) respectively. The Hemizona assay was then utilized to compare
      sperm-zona binding post processing. RESULTS: Evaluation of sperm parameters
      indicated that rhProtease did not, at any of the tested concentrations, have an
      impact on (i) mitochondrial membrane potential, vitality, motility, or (ii) zona
      binding potential. CONCLUSION: We report that the addition of rhProtease to
      density gradients is a non-detrimental approach that could improve the
      effectiveness of semen processing for the elimination of seminal pathogens, and
      benefit assisted reproduction outcome.

PMID- 22956336
TI  - Striving for educational and career goals during the transition after high
      school: what is beneficial?
AB  - The present study takes a motivational perspective that views youths' educational
      and career engagement as influential and potentially competing for the same
      motivational resources in the transition to adulthood. We investigated whether
      motivational engagement with educational and career goals in the year after high
      school graduation was differentially associated with educational, career-related
      and subjective well-being outcomes 2 and 4 years after school graduation. Our
      longitudinal study of a multi-ethnic sample of Los Angeles high-school graduates
      followed participants 2 years (N = 561; 61.5 % female) and 4 years (N = 364; 59.8
      % female) after high school graduation. The findings indicate that motivational
      engagement with educational goals after high school graduation predicted
      educational attainments and psychological well-being at follow-up 2 and 4 years
      after graduation, and occupational progress at 4 years after graduation. Work
      hours assessed shortly after high school graduation were associated with poorer
      educational outcomes both at 2 and 4 years after high school. Occupational goal
      engagement was not associated with better outcomes, but predicted less
      educational attainment 4 years after graduating. Thus, educational goal
      engagement predicted favorable outcomes, whereas career-related goal engagement
      for the most part was neutral with some select associations with negative
      educational outcomes. A strong motivational commitment to educational goals, but
      not to career goals, is an important component of a successful transition to
      adulthood.

PMID- 22956337
TI  - Predicting homophobic behavior among heterosexual youth: domain general and
      sexual orientation-specific factors at the individual and contextual level.
AB  - As a form of bias-based harassment, homophobic behavior remains prominent in
      schools. Yet, little attention has been given to factors that underlie it, aside
      from bullying and sexual prejudice. Thus, we examined multiple domain general
      (empathy, perspective-taking, classroom respect norms) and sexual orientation
      specific factors (sexual orientation identity importance, number of sexual
      minority friends, parents' sexual minority attitudes, media messages). We
      documented support for a model in which these sets of factors converged to
      predict homophobic behavior, mediated through bullying and prejudice, among 581
      students in grades 9-12 (55 % female). The structural equation model indicated
      that, with the exception of media messages, these additional factors predicted
      levels of prejudice and bullying, which in turn predicted the likelihood of
      students to engage in homophobic behavior. These findings highlight the
      importance of addressing multiple interrelated factors in efforts to reduce
      bullying, prejudice, and discrimination among youth.

PMID- 22956338
TI  - Evaluation of the thoracic aortic dissection treated by endografts covering a
      longer distance of aorta according to the location of the Adamkiewicz artery.
AB  - BACKGROUND: Presurgical locating the Adamkiewicz artery (AKA) will be very
      helpful for thoracic aortic endovascular repair. This study aimed to evaluate the
      effects of using longer endografts according to location of AKA on outcomes of
      endovascular treatment for thoracic aortic dissection. METHODS: A total of 217
      patients (143 men, 74 women; mean age: 65 +/- 11 years) with type B dissection
      were divided into two groups according to whether the AKA was identified or not
      presurgically. Endovascular repairs were performed for all patients. Distal
      landing levels of endograft were recorded. The thrombosis of false lumen and the
      complications of spinal cord ischemia and endoleak were analyzed. RESULTS: The
      AKA was detected in 121 (55.8%) patients (group A) and not detected in 96 (44.2%)
      patients (group B). According to the levels of AKA, patients in group A obtained
      the stabilization of the affected thoracic aorta over a longer distance. The
      ratio of patients with distal landing levels at T8-T10 was significantly higher
      than in group B (59.5 vs. 12.5%, chi2 = 49.85, p < 0.01). Also, during the follow
      up to 7.3 months, the ratio of patients with total thrombosis of false lumen in
      group A was significantly higher than group B (32.1 vs. 19.1%, chi2 = 4.34, p =
      0.037). CONCLUSIONS: Accurate preoperative knowledge of AKA is extremely useful
      for selecting a longer device to provide a better structural stability of
      affected aorta and promote false lumen thrombosis during a midterm follow-up
      phase.

PMID- 22956339
TI  - Medical manuscripts impact of hospice enrollment on cost and length of stay of a
      terminal admission.
AB  - OBJECTIVE: To determine whether hospice enrollment at the time of a terminal
      admission alters the length of stay (LOS) or costs compared with patients not
      enrolled in hospice. METHODS: Retrospective chart review of all nontraumatic
      inpatient deaths of patients with a previous admission in the preceding 12 months
      at an academic hospital. RESULTS: 209 patients had a nontraumatic death and an
      admission in the year prior to the terminal admission. Patients enrolled in
      hospice had a shorter LOS (P = .02) and lower cost (P < .0001) than patients not
      enrolled at the time of their terminal admission. CONCLUSIONS: Enrollment in
      hospice during a terminal admission decreased cost and LOS. Hospice may be a way
      to provide more cost-effective, appropriate care to dying patients.

PMID- 22956340
TI  - The experiences of suffering of palliative care patients in Malaysia: a thematic
      analysis.
AB  - A qualitative study was conducted with semi-structured interviews to explore the
      experiences of suffering in 20 adult palliative care inpatients of University
      Malaya Medical Centre. The results were thematically analyzed. Ten basic themes
      were generated (1) loss and change -> differential suffering, (2) care dependence
      -> dependent suffering, (3) family stress -> empathic suffering, (4) disease and
      dying -> terminal suffering, (5) health care staff encounters -> interactional
      suffering, (6) hospital environment -> environmental suffering, (7) physical
      symptoms -> sensory suffering, (8) emotional reactions -> emotional suffering,
      (9) cognitive reactions -> cognitive suffering, and (10) spiritual reactions ->
      spiritual suffering. An existential-experiential model of suffering was
      conceptualized from the analysis. This model may inform the development of
      interventions in the prevention and management of suffering.

PMID- 22956341
TI  - Biomarkers classification and therapeutic decision-making for malignant gliomas.
AB  - OPINION STATEMENT: Diffuse gliomas are the most common primary brain tumors, with
      glioblastoma (GBM) encompassing more than 50 % of all cases. Despite aggressive
      therapy, patients nearly always succumb to their disease and the survival for
      patients with GBM is approximately 1 year. During past years, numerous scientific
      contributions have reshaped the field of neuro-oncology and neuropathology. A
      series of molecular discoveries have shed light on new pathogenic mechanisms, as
      well as new prognostic and predictive biomarkers with clinical relevance. The
      current World Health Organization (WHO) classification system is solely based on
      morphologic criteria; however, there is accumulated evidence that tumors with
      similar histology have distinct molecular signatures with a clinically
      significant impact on treatment response and survival. Molecular markers and
      signatures could be incorporated into the glioma classification and grading
      system to mirror the clinical outcomes. Additionally, molecular markers could
      lead to a redefinition of currently controversial entities, such as mixed
      oligoastrocytomas. Newly discovered molecular alterations also have the potential
      to become targets for future drug development. Despite tremendous progress in the
      past decade, therapeutic progress for diffuse gliomas has been slow. A further
      understanding of glioma biology, in concert with well-designed clinical trials,
      is necessary to identify more putative molecular biomarkers and unravel the
      mysteries in the pathogenic mechanisms that trigger this menacing disease.

PMID- 22956342
TI  - Preconditioning with diosgenin and treadmill exercise preserves the cardiac
      toxicity of isoproterenol in rats.
AB  - This study was aimed to evaluate the preventive effect of diosgenin and exercise
      on tissue antioxidant status in isoproterenol-induced myocardial infarction (MI)
      in male Wistar rats. Levels of lipid peroxides, reduced glutathione (GSH), and
      the activities of glutathione-dependent antioxidant enzymes (glutathione
      peroxidise and glutathione reductase) and antiperoxidative enzymes (catalase and
      superoxide dismutase) in the plasma and the heart tissue of experimental groups
      of rats were determined. Pretreatment with diosgenin and exercise exerted an
      antioxidant effect against isoproterenol-induced myocardial infarction by
      blocking the induction of lipid peroxidation. A tendency to prevent the
      isoproterenol-induced alterations in the level of GSH, in the activities of
      glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also
      observed. Histopathological findings of the myocardial tissue showed a protective
      role for combination of diosgenin and exercise in isoproterenol (ISO)-treated
      rats. Thus, the present study reveals that preconditioning with diosgenin and
      exercise exerts cardioprotective effect against ISO-induced MI due to its free
      radical scavenging and antioxidant effects, which maintains the tissue defense
      system against myocardial damage.

PMID- 22956344
TI  - Overshadowing and associability change: examining the contribution of
      differential stimulus exposure.
AB  - In two appetitive conditioning experiments with rats, we investigated the
      mechanisms responsible for demonstrations of the superior associability of
      overshadowed conditioned stimuli (CSs) relative to control CSs. In Experiment 1,
      we investigated whether previous demonstrations were a consequence of differences
      in the relationship between the CSs and the unconditioned stimulus (US) or of
      differences in the conditions of exposure to the CSs. Rats received trials with
      X, Y, and an AB compound, but no delivery of the US (X-, Y-, AB-). A subsequent
      AY-, AX+, BY + test discrimination revealed that the AY/BY component of the
      discrimination was solved more readily than the AY/AX component--suggesting the
      contribution of an exposure effect. In Experiment 2, we better equated the
      conditions of exposure between A and Y by using AB+, XY+, X- training in Stage 1.
      In Stage 2, instrumental responses were rewarded during an AY compound. A final
      test revealed that Y took better control of instrumental responding than did A.
      The results of these experiments are discussed in terms of classical and
      contemporary theories of learning and attention.

PMID- 22956343
TI  - Clinical features of hepatocellular carcinoma supplied by the left internal
      mammary artery.
AB  - PURPOSE: To evaluate the clinical features of hepatocellular carcinoma (HCC)
      supplied by the left internal mammary artery (LIMA). MATERIALS AND METHODS: This
      cohort included 12 HCCs of 12 patients supplied by the LIMA. The clinical
      features of these tumors were analyzed. RESULTS: The tumor diameters were 4.2 +/-
      4.4 cm (mean +/- SD) located at the surface of segments 4 (n = 6), 3 (n = 3), 2
      (n = 2), and 4-8 (n = 1), respectively. The tumor was supplied by the phrenic
      branch (n = 8) or musclophrenic artery (n = 4) entirely (n = 7) or partially (n =
      5). Two patients with large tumors 10 and 16 cm in diameter, respectively,
      received no previous treatment. Ten patients had previously undergone 5.8 +/- 3.7
      TACE sessions including through extrahepatic collaterals. Selective TACE could
      not be completed in one. No TACE-related complications developed. Of 11 embolized
      tumors, six did not recur at 8.8 +/- 4.6 months and five recurred 4.4 +/- 2.6
      months later. CONCLUSION: The clinical features of HCC supplied by the LIMA can
      be divided into two categories, untreated large tumors and small tumors receiving
      multiple TACE sessions at the subcapsular area of the left hepatic lobe.

PMID- 22956345
TI  - Use of vitamin D in various disorders.
AB  - Approximately 1 billion people worldwide have been identified as vitamin D
      deficient in the 21st century, and the number is on the rise; non-classical
      actions of vitamin D were initially recognized around 30 y ago when receptors for
      vitamin D were detected in neoplastic cells lines. The aim of this review is to
      provide a brief overview of the non-classical actions of vitamin D. Reports
      describing the associations of non skeletal actions of vitamin D, especially
      pertaining to the immune system, inflammatory disorders, cancers and
      cardiovascular disease have been summarized in this paper. Reports support a role
      for the active form of vitamin D in mediating normal function of both the innate
      and adaptive immune systems. Studies also suggest a link between vitamin D
      deficiency and autoimmune diseases, such as rheumatoid arthritis, systemic
      sclerosis, systemic lupus erythematosus and type 1 diabetes. There is believed to
      be an inverse association between serum 25-hydroxyvitamin D concentrations and
      the incidence of colorectal cancer, sporadic colorectal adenoma and breast
      cancer. Vitamin D deficiency has been linked with various cardiovascular diseases
      such as hypertension, myocardial infarction, and stroke. Several epidemiological
      and genetic studies suggest a strong association between vitamin D and non
      skeletal acute and chronic disorders. However, currently, robust clinical data
      are still lacking to support raising intake requirements and target vitamin D
      plasma levels. Nonetheless, the high prevalence of vitamin D deficiency is
      alarming and requires implementation of clear supplementation guidelines.

PMID- 22956346
TI  - Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex
      steroid feedback.
AB  - STUDY QUESTION: Does sex-steroid feedback influence gonadotrophin responses to
      kisspeptin-10? SUMMARY ANSWER: Gonadotrophin response to kisspeptin-10 is
      enhanced in sex-steroid deficient post-menopausal women and suppressed in women
      taking pharmacological doses of exogenous estrogen and progestogen. WHAT IS KNOWN
      ALREADY: Kisspeptin, a novel hypothalamic neuropeptide, stimulates gonadotrophin
      secretion by stimulating GnRH secretion and has been shown in animal models to
      play a pivotal role in mediating sex steroid feedback. As estrogen feedback
      occurs at both the hypothalamus and the pituitary levels, we hypothesized that
      the stimulatory effect of kisspeptin-10 in women would be dependent on prevailing
      sex steroid milieu. STUDY DESIGN, SIZE, DURATION: An experimental study of a
      novel neuropeptide in women-10 in the early follicular phase, 6 post-menopausal
      and 8 taking sex-steroid contraceptives (combined pill, n = 4; progestogen
      implants, n = 4) with suppressed LH secretion. Gonadotrophin secretion was
      followed for 60 min after kisspeptin administration. METHODS AND PARTICIPANTS:
      The gonadotrophin response to intravenous kisspeptin-10 (0.3 ug/kg) in women in
      the early follicular phase was compared with that in the presence of low
      endogenous sex steroids/high gonadotrophin secretion (post-menopausal women) and
      in women taking sex-steroid contraceptives (combined pill, n = 4; progestogen
      implants, n = 4) with suppressed LH secretion. Area under the curve (AUC) of
      gonadotrophin secretion sampled at 15 min intervals over 60 min before and after
      kisspeptin-10 was analysed. MAIN RESULTS AND ROLE OF CHANCE: Kisspeptin-10
      stimulated LH secretion in follicular (DeltaAUC 2.3 +/- 0.8 IU/l h, P = 0.009),
      post-menopausal (5.3 +/- 0.9 IU/l h P 0.002) and progestogen (2.6 +/- 0.8 IU/l h
      P 0.05) groups but not in women taking combined pill (0.9 +/- 0.4 IU/l h P 0.13).
      FSH secretion was significantly increased only in post-menopausal women (DeltaAUC
      2.6 +/- 0.8 IU/l h P = 0.03) with changes of <0.5 IU/l h observed in the other
      three groups. Both LH and FSH responses in post-menopausal women were
      significantly larger than the other groups (one-way ANOVA analysis of DeltaAUC;
      LH (P = 0.012) and FSH (P = 0.001)]. LIMITATIONS, REASONS FOR CAUTION: This study
      only assessed acute responses to an intravenous bolus of kisspeptin-10
      administration, and the impact of continuous exposure to kisspeptin-10 on LH
      pulse frequency in women remains to be studied to fully understand the
      translational potential. WIDER IMPLICATIONS OF THE FINDINGS: Gonadotrophin
      secretion in women is stimulated by kisspeptin-10. These results suggest that the
      pituitary gonadotrope is a functionally important locus of estrogen feedback in
      women and also inform potential translational applications of kisspeptin in
      reproductive endocrine disorders. STUDY FUNDING: Medical Research Council (UK).
      COMPETING INTERESTS: None.

PMID- 22956347
TI  - TNF receptors regulate vascular homeostasis in zebrafish through a caspase-8,
      caspase-2 and P53 apoptotic program that bypasses caspase-3.
AB  - Although it is known that tumor necrosis factor receptor (TNFR) signaling plays a
      crucial role in vascular integrity and homeostasis, the contribution of each
      receptor to these processes and the signaling pathway involved are still largely
      unknown. Here, we show that targeted gene knockdown of TNFRSF1B in zebrafish
      embryos results in the induction of a caspase-8, caspase-2 and P53-dependent
      apoptotic program in endothelial cells that bypasses caspase-3. Furthermore, the
      simultaneous depletion of TNFRSF1A or the activation of NF-kappaB rescue
      endothelial cell apoptosis, indicating that a signaling balance between both
      TNFRs is required for endothelial cell integrity. In endothelial cells, TNFRSF1A
      signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF
      kappaB. Similarly, TNFalpha promotes the apoptosis of human endothelial cells
      through TNFRSF1A and triggers caspase-2 and P53 activation. We have identified an
      evolutionarily conserved apoptotic pathway involved in vascular homeostasis that
      provides new therapeutic targets for the control of inflammation- and tumor
      driven angiogenesis.

PMID- 22956348
TI  - Efficacy of low dose hCG on oocyte maturity for ovarian stimulation in poor
      responder women undergoing intracytoplasmic sperm injection cycle: a randomized
      controlled trial.
AB  - PURPOSE: To investigate the effect of late follicular administration of low dose
      hCG on oocyte maturity in poor responding women undergoing intracytoplasmic sperm
      injection (ICSI). MATERIALS AND METHODS: This prospective randomized pilot trial
      was performed on 73 poor responders undergoing ICSI, in Reproductive Biomedicine
      Research Center, Royan Institute, Tehran, Iran. All eligible patients underwent a
      GnRH-a long protocol and were randomly allocated into three study groups for
      ovarian stimulation: groupA received recombinant FSH alone, group B received
      recombinant FSH supplemented by 100 IU hCG. Group C received recombinant FSH
      supplemented by 200 IU hCG. The main endpoint was the number of metaphase II
      oocytes retrieved. RESULTS: Of 78 poor responding patients entered to this study,
      73 women were considered eligible for enrolment. Of these, 26 women were
      allocated to receive only recombinant FSH, 24 patients allocated to receive
      recombinant FSH and 100 IU hCG and 23 patients were assigned to receive
      recombinant FSH and 200 IU hCG. Number of oocytes retrieved were significantly
      higher in group B compared to group A (6.5 +/- 3.3 versus 4.0 +/- 2.3; P = .03).
      Other cycle and clinical outcomes were comparable between three groups.
      CONCLUSIONS: The present study demonstrated that adding 100 IU hCG to rFSH in a
      GnRH agonist cycle in poor responders improve response to stimulation whereas the
      number of metaphase II oocytes remains comparable between groups. The existence
      of a possible trend toward higher mature oocytes and lower total dosage rFSH in
      patients received 100 or 200 IU hCG is probably due to the small sample size that
      means further large clinical trials in a more homogenous population is required
      (clinical trial registration number; NCT01509833).

PMID- 22956350
TI  - Pharmacokinetics of febuxostat in healthy Chinese volunteers.
AB  - BACKGROUND: Febuxostat is a novel non-purine selective inhibitor of xanthine
      oxidase developed for the management of hyperuricemia in patients with gout.
      OBJECTIVE: To investigate the pharmacokinetics and also evaluate the effects of
      gender and food on the pharmacokinetics of febuxostat in healthy Chinese
      volunteers. METHODS: A phase I, 3-period study was performed in healthy Chinese
      male and female subjects. Subjects either received single 40 mg, multiple 40 mg
      and single 80 mg doses of febuxostat under fasted conditions, or received single
      80 mg doses under fed condition. Plasma concentrations of febuxostat were
      collected and determined at 14 time points over 48 h. RESULTS: After 40 mg and 80
      mg single dose administration of febuxostat, the C max were 2.308+/-0.812 and
      4.559+/-1.246 MUg/mL, the T max were 1.6+/-0.6 and 2.1+/-1.0 h, the t 1/2 were
      6.8+/-1.7 and 6.7+/-1.9 h, and the AUC0-infinity were 7.704+/-1.723 and 16.34+/
      3.87 MUg?h/mL, respectively. In the multiple-dose study at 40 mg dose for 6
      consecutive days, the mean (SD) steady-state pharmacokinetic parameters on day 8
      were similar to those following a single dose of febuxostat on day 1. In
      addition, food caused a decrease of 33% for C max and a delay of 0.3 h for T max.
      Gender had no significant effect on the pharmacokinetics of febuxostat.
      Febuxostat was well tolerated over the investigated dose range. CONCLUSION:
      Compared with the previous study, the pharmacokinetics of febuxostat appeared to
      be different between Chinese and other races.

PMID- 22956349
TI  - A simple recipe for the non-expert bioinformaticist for building experimentally
      testable hypotheses for proteins with no known homologs.
AB  - The study of the protein-protein interactions (PPIs) of unique ORFs is a strategy
      for deciphering the biological roles of unique ORFs of interest. For uniform
      reference, we define unique ORFs as those for which no matching protein is found
      after PDB-BLAST search with default parameters. The uniqueness of the ORFs
      generally precludes the straightforward use of structure-based approaches in the
      design of experiments to explore PPIs. Many open-source bioinformatics tools,
      from the commonly-used to the relatively esoteric, have been built and validated
      to perform analyses and/or predictions of sorts on proteins. How can these
      available tools be combined into a protocol that helps the non-expert
      bioinformaticist researcher to design experiments to explore the PPIs of their
      unique ORF? Here we define a pragmatic protocol based on accessibility of
      software to achieve this and we make it concrete by applying it on two proteins
      the ImuB and ImuA' proteins from Mycobacterium tuberculosis. The protocol is
      pragmatic in that decisions are made largely based on the availability of easy-to
      use freeware. We define the following basic and user-friendly software pathway to
      build testable PPI hypotheses for a query protein sequence: PSI-PRED -> MUSTER ->
      metaPPISP -> ASAView and ConSurf. Where possible, other analytical and/or
      predictive tools may be included. Our protocol combines the software predictions
      and analyses with general bioinformatics principles to arrive at consensus,
      prioritised and testable PPI hypotheses.

PMID- 22956351
TI  - Some novel anticonvulsant agents derived from phthalazinedione.
AB  - A series of phthalazinedione bearing substituted oxadiazole moiety derivatives
      X(1-7) were synthesized in good yield and evaluated for their possible
      anticonvulsant activity. The structures of the synthesized compounds were
      confirmed on the basis of their spectral data and elemental analysis. Their
      anticonvulsant activities were evaluated by the maximal electroshock induced
      seizure (MES) and subcutaneous pentylenetetrazole (PTZ) tests. All the tested
      compounds showed considerable anticonvulsant activities in at least one of the
      anticonvulsant tests. Moreover, some of the tested compounds exhibited moderate
      anticonvulsant activities in both MES and PTZ tests. From these results,[3-)2
      Alkoxycarbonylmethylthioxadiozol-5-yl)methyl -6-Iodophthalazine - 1,4- (2H,3H)
      1,4-dion] (X1-7) derivatives could be recommended as novel structures of broad
      spectrum anticonvulsants.

PMID- 22956352
TI  - Hypolipidemic and antioxidative effects of noni (Morinda citrifolia L.) juice on
      high- fat/cholesterol-dietary hamsters.
AB  - Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and
      antioxidative effects of NJ were investigated in this study. Fifty male hamsters
      were assigned randomly to one of the following groups: (1) normal diet and
      distilled water (LFCD); (2) high-fat/cholesterol diet and distilled water (HFCD);
      (3) HFCD and 3 ml NJ (including 0.20 g solids)/kg BW (NJ_L); (4) HFCD and 6 mL NJ
      (including 0.40 g solids)/kg BW (NJ_M); (5) HFCD and 9 ml NJ (including 0.60 g
      solids)/kg BW (NJ_H) for six weeks. NJ supplementation decreased (p < 0.05) serum
      triacylglycerol, cholesterol, atherogenic index, malondialdehyde levels, and
      hepatic lipids in HFCD hamsters, whereas serum trolox equivalent antioxidant
      capacity, glutathione, and fecal lipids in HFCD hamsters were increased (p <
      0.05) by NJ supplementation. Although NJ supplementation downregulated (p < 0.05)
      sterol regulator element binding protein-1c in HFCD hamsters, it upregulated (p <
      0.05) hepatic peroxisome proliferator-activated receptor-alpha and uncoupling
      protein 2 gene expressions in HFCD hamsters. Results demonstrate that NJ promotes
      cardioprotection in a high-fat/cholesterol diet.

PMID- 22956354
TI  - A preliminary and qualitative metallomics study of mercury in the muscle of fish
      from Amazonas, Brazil.
AB  - This paper presents preliminary findings for a metallomics study of mercury in
      the muscle of the fish species from Amazonas, Brazil, after protein separation by
      two-dimensional polyacrylamide gel electrophoresis and subsequent evaluation of
      mercury by synchrotron radiation X-ray fluorescence. The fluorescence spectra
      revealed mercury in two protein spots. The mercury-containing protein spots
      showed molecular weights of 20.8 +/- 0.7 and 19.8 +/- 0.5 kDa and isoelectric
      points of 5.6 +/- 0.2 and 7.5 +/- 0.3, respectively.

PMID- 22956356
TI  - A CAD interface for GEANT4.
AB  - Often CAD models already exist for parts of a geometry being simulated using
      GEANT4. Direct import of these CAD models into GEANT4 however, may not be
      possible and complex components may be difficult to define via other means.
      Solutions that allow for users to work around the limited support in the GEANT4
      toolkit for loading predefined CAD geometries have been presented by others,
      however these solutions require intermediate file format conversion using
      commercial software. Here within we describe a technique that allows for CAD
      models to be directly loaded as geometry without the need for commercial software
      and intermediate file format conversion. Robustness of the interface was tested
      using a set of CAD models of various complexity; for the models used in testing,
      no import errors were reported and all geometry was found to be navigable by
      GEANT4.

PMID- 22956355
TI  - Screening of anaerobic activities in sediments of an acidic environment: Tinto
      River.
AB  - The Tinto River (Huelva, Spain) is a natural acidic rock drainage environment
      produced by the bio-oxidation of metallic sulfides from the Iberian Pyritic Belt.
      A geomicrobiological model of the different microbial cycles operating in the
      sediments was recently developed through molecular biological methods, suggesting
      the presence of iron reducers, methanogens, nitrate reducers and hydrogen
      producers. In this study, we used a combination of molecular biological methods
      and targeted enrichment incubations to validate this model and prove the
      existence of those potential anaerobic activities in the acidic sediments of
      Tinto River. Methanogenic, sulfate-reducing, denitrifying and hydrogen-producing
      enrichments were all positive at pH between 5 and 7. Methanogenic enrichments
      revealed the presence of methanogenic archaea belonging to the genera
      Methanosarcina and Methanobrevibacter. Enrichments for sulfate-reducing
      microorganisms were dominated by Desulfotomaculum spp. Denitrifying enrichments
      showed a broad diversity of bacteria belonging to the genera Paenibacillus,
      Bacillus, Sedimentibacter, Lysinibacillus, Delftia, Alcaligenes, Clostridium and
      Desulfitobacterium. Hydrogen-producing enrichments were dominated by Clostridium
      spp. These enrichments confirm the presence of anaerobic activities in the acidic
      sediments of the Tinto River that are normally assumed to take place exclusively
      at neutral pH.

PMID- 22956357
TI  - PhysioScripts: an extensible, open source platform for the processing of
      physiological data.
AB  - A commonality across research involving physiological measures is the need to
      process large amounts of data. Such data processing typically involves the use of
      software tools to achieve several methodological steps, including identifying and
      correcting artifacts and defining epochs of time for the reduction and analysis
      of one or more physiological measures. This article describes a new tool to aid
      in the processing of physiological data: PhysioScripts. Key elements of
      PhysioScripts include a graphical interface to view and edit the results of
      processing steps, as well as a flexible framework to automate the creation of
      uniform or variable length epochs. The software comprises freely available
      scripts implemented in the R computing environment. Consequently, PhysioScripts
      can be readily modified to process other data types through the addition of new
      subroutines that can be plugged into the existing data processing framework. For
      illustrative purposes, we describe the steps involved in two data processing
      examples: (1) heart rate variability from the electrocardiogram and (2)
      respiratory rate derived from a chest strain gauge. The software, accompanying
      documentation, and an example data set are available online at
      israelchristie.com/software.

PMID- 22956358
TI  - Classification accuracy and consistency of computerized adaptive testing.
AB  - In this article, four item selection methods in computerized adaptive testing are
      examined in terms of classification accuracy and consistency, including two
      popular heuristics for constraint management, the maximum priority index (MPI)
      method and the weighted deviation modeling method, as well as the widely known
      maximum Fisher information method and randomized item selection as baselines.
      Results suggest that the MPI method is able to meet constraints and keep test
      overlap rate low. Among the four methods, it is the only one that manages to
      produce parallel forms in terms of content coverage and, consequently, the only
      method to which the idea of classification consistency applies. With tests as
      short as 12 items, the MPI method does fairly well in classifying examinees
      accurately and consistently. Its performance improves with longer tests. The
      effects of number of decision categories and cut score locations are also
      examined. Recommendations are made in the Discussion section.

PMID- 22956359
TI  - Norms of valence, arousal, dominance, and age of acquisition for 4,300 Dutch
      words.
AB  - This article presents norms of valence/pleasantness, activity/arousal,
      power/dominance, and age of acquisition for 4,300 Dutch words, mainly nouns,
      adjectives, adverbs, and verbs. The norms are based on ratings with a 7-point
      Likert scale by independent groups of students from two Belgian (Ghent and
      Leuven) and two Dutch (Rotterdam and Leiden-Amsterdam) samples. For each
      variable, we obtained high split-half reliabilities within each sample and high
      correlations between samples. In addition, the valence ratings of a previous,
      more limited study (Hermans & De Houwer, Psychologica Belgica, 34:115-139, 1994)
      correlated highly with those of the present study. Therefore, the new norms are a
      valuable source of information for affective research in the Dutch language.

PMID- 22956360
TI  - Parsing eye-tracking data of variable quality to provide accurate fixation
      duration estimates in infants and adults.
AB  - Researchers studying infants' spontaneous allocation of attention have
      traditionally relied on hand-coding infants' direction of gaze from videos; these
      techniques have low temporal and spatial resolution and are labor intensive. Eye
      tracking technology potentially allows for much more precise measurement of how
      attention is allocated at the subsecond scale, but a number of technical and
      methodological issues have given rise to caution about the quality and
      reliability of high temporal resolution data obtained from infants. We present
      analyses suggesting that when standard dispersal-based fixation detection
      algorithms are used to parse eye-tracking data obtained from infants, the results
      appear to be heavily influenced by interindividual variations in data quality. We
      discuss the causes of these artifacts, including fragmentary fixations arising
      from flickery or unreliable contact with the eyetracker and variable degrees of
      imprecision in reported position of gaze. We also present new algorithms designed
      to cope with these problems by including a number of new post hoc verification
      checks to identify and eliminate fixations that may be artifactual. We assess the
      results of our algorithms by testing their reliability using a variety of methods
      and on several data sets. We contend that, with appropriate data analysis
      methods, fixation duration can be a reliable and stable measure in infants. We
      conclude by discussing ways in which studying fixation durations during
      unconstrained orienting may offer insights into the relationship between
      attention and learning in naturalistic settings.

PMID- 22956363
TI  - Performance of a semiconductor SPECT system: comparison with a conventional Anger
      type SPECT instrument.
AB  - OBJECTIVE: The performance of a new single photon emission computed tomography
      (SPECT) scanner with a cadmium-zinc-telluride (CZT) solid-state semiconductor
      detector (Discovery NM 530c; D530c) was evaluated and compared to a conventional
      Anger-type SPECT with a dual-detector camera (Infinia). METHODS: Three different
      phantom studies were performed. Full width at half maximum (FWHM) was measured
      using line sources placed at different locations in a cylindrical phantom.
      Uniformity was measured using cylindrical phantoms with 3 different diameters
      (80, 120, and 160 mm). Spatial resolution was evaluated using hot-rod phantoms of
      various diameters (5, 9, 13, 16, and 20 mm). Three different myocardial phantom
      studies were also performed, acquiring projection data with and without defects,
      and evaluating the interference of liver and gallbladder radioactivity. In a
      clinical study, the D530c employed list-mode raw data acquisition with
      electrocardiogram (ECG)-gated acquisition over a 10-min period. From the 10-min
      projection data, 1-, 3-, 5-, 7- and 10-min SPECT images were reconstructed.
      RESULTS: The FWHM of the D503c was 1.73-3.48 mm (without water) and 3.88-6.64 mm
      (with water), whereas the FWHM of the Infinia was 8.17-12.63 mm (without water)
      and 15.48-16.28 mm (with water). Non-uniformity was larger for the D530c than for
      the Infinia. Truncation artifacts were also observed with the D530c in a Phi160
      mm phantom. The contrast ratio, as defined by myocardial defect/non-defect ratio,
      was better for the D530c than for the Infinia, and the influence from liver and
      gallbladder radioactivities was less. Quantitative gated SPECT (QGS) software
      demonstrated significant differences between data captured over a 10-min period,
      relative to those acquired over periods of <5 min; there was no difference
      between ejection fractions calculated using data capture for periods >=5 min (p <
      0.05). CONCLUSIONS: The D530c is superior to the Infinia, with regard to both
      spatial resolution and sensitivity. In this study, these advantages were
      confirmed by the myocardial phantom and in a clinical setting, using the QGS
      software.

PMID- 22956364
TI  - Social-emotional support, life satisfaction, and mental health on reproductive
      age women's health utilization, US, 2009.
AB  - To examine the associations among social-emotional support, life satisfaction,
      and mental health with not having a routine checkup among women of reproductive
      age in the US, data from the 2009 Behavioral Risk Factor Surveillance System, a
      population-based telephone survey of health behaviors, were analyzed among
      reproductive aged (18-44 years) women in the US. Prevalence estimates were
      calculated for not having a routine checkup in the past year with measures of
      social-emotional support, life satisfaction, and mental distress. Independent
      multivariable logistic regressions for each measure assessed not having a routine
      checkup within the past year with adjustment for age, race/ethnicity, education
      level, and health care coverage. Among women of reproductive age, 33.7 % (95 % CI
      33.0-34.4) did not have a routine checkup within the past year. Factors
      associated with not having a routine checkup included: having social-emotional
      support most of the time (AOR = 1.29, 95 % CI 1.20-1.38) or sometimes or less
      (AOR = 1.47, 95 % CI 1.34-1.61) compared to those who reported always having the
      social-emotional support they need; reporting life satisfaction as being
      satisfied (AOR = 1.27, 95 % CI 1.19-1.36) or dissatisfied (AOR = 1.65, 95 % CI
      1.43-1.91) compared to being very satisfied; and frequent mental distress (AOR =
      1.19, 95 % CI 1.09-1.30) compared to those without. Women who report lower levels
      of social-emotional support, less life satisfaction, and frequent mental distress
      are less likely to see a doctor for a routine checkup. Targeted outreach that
      provides appropriate support are needed so these women can access clinical
      services to increase exposure to preventive health opportunities and improve
      overall health.

PMID- 22956365
TI  - Factors influencing women's decision to seek antenatal care in the Andes of Peru.
AB  - This qualitative study aimed to assess factors influencing pregnant women's
      decision to seek or avoid antenatal care (ANC) in the Andes of Peru. Open-ended,
      semi-structured interviews were conducted with 24 women utilizing ANC (+) and 10
      women avoiding ANC (-). Interviews were translated to English from Quechua and
      Spanish, transcribed, and analyzed using grounded theory. Factors influencing ANC
      women included: expecting criticism for having additional children; long ANC
      wait time and inconvenient hours of operation; and masculine gender of health
      workers. For ANC+ women, motivating factors included: maximizing positive health
      outcomes; past negative maternity experiences; pressure from family members; and
      avoidance of rumored fines or fees associated with ANC non-attendance and in
      hospital deliveries, respectively. Both ANC+ and ANC- women were fearful and
      embarrassed about possible criticism for having additional children and the
      gender of the health workers, yet they weighed these factors differently. To
      better understand how rural women make decisions about ANC attendance, it is
      important to consider the value they place on the factors influencing their
      decision, and their emotional assessment of such issues.

PMID- 22956366
TI  - T2-weighted and delayed enhancement MRI of eosinophilic myocarditis: relationship
      with clinical phases and global cardiac function.
AB  - PURPOSE: To evaluate the usefulness of magnetic resonance imaging (MRI) for
      detection and quantification of myocardial damage related to clinical phases and
      cardiac function during eosinophilic myocarditis. MATERIALS AND METHODS: Four
      eosinophilic myocarditis patients received seven MRI studies. The left
      ventricular myocardium was divided into 48 layers, and we quantified the extent
      of abnormal intensity detected by T2-weighted or delayed enhancement MRI relative
      to the clinical phase and global cardiac function. RESULTS: T2-weighted imaging
      detected extensive myocardial hyperintensity during the acute phase of
      eosinophilic myocarditis. Diffuse myocardial delayed enhancement was observed in
      one patient during the acute phase, but not in the other. Little or no
      hyperintensity was detected by T2-weighted imaging or myocardial delayed
      enhancement during the convalescent phase. The extent of hyperenhancing
      myocardial layers was inversely correlated with the ejection fraction (EF) (r = 
      0.87). CONCLUSION: MRI can evaluate the presence and extent of myocardial damage
      related to the clinical phases and EF during eosinophilic myocarditis.

PMID- 22956367
TI  - The possibility of perfect prescriptions?

PMID- 22956368
TI  - Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of
      primary cutaneous melanoma is associated with increased thickness and disease
      progression.
AB  - Loss of E-cadherin expression in melanoma correlates with increased tumor
      thickness and reduced disease-free survival. The molecular mechanisms
      underpinning its differential expression in melanoma tissue remain elusive.
      MicroRNAs (miRNAs) have been implicated in tumor progression and regulation of E
      cadherin expression. Here, we demonstrate a significant correlation between tumor
      thickness and loss of expression of miR-200a, miR-200c, and miR-203 in a series
      of 23 frozen primary melanomas, where it was confirmed in two subsequent
      validation series (series 1: six nevi, 15 primary melanomas, and 16 metastases;
      series 2: 11 matched pairs of primary melanomas and metastases). Decreased levels
      of miR-200a, miR-200c, and miR-203 correlated with increasing thickness in the
      combined validation series (P = 0.024, 0.033, and 0.031, respectively). In
      addition, progressive loss of miR-200a expression with disease progression was
      observed in series 1 (P < 0.001) and in series 2 (P = 0.029). MiR-200 in situ
      hybridization and E-cadherin immunohistochemistry demonstrated reduced expression
      of both at the deep invasive margin of the tumor. Furthermore, a functional
      validation study using an anti-miR200 strategy demonstrated that loss of miR-200
      expression in melanoma cell lines reduced E-cadherin expression. Collectively,
      our data point towards an important role for miR-200 and miR203 expression in
      regulating E-cadherin during melanoma progression.

PMID- 22956369
TI  - The diagnostic protocol for evaluation of periprosthetic joint infection.
AB  - Infection is becoming the most important as well as the most devastating
      mechanism of prosthetic joint failure. The incidence is increasing because the
      absolute number of patients operated is increasing and because more often very
      sick, debilitated and immunocompromised patients are operated. The trend reveals
      a further increase in the years to come. Diagnosis may be very easy in case of
      high grade processes, but also extremely difficult in some other instances.
      Misdiagnosing infection leads to repeated early failures that are distressing for
      patients as well as surgeons. To avoid failures related to misdiagnosed
      prosthetic joint infections a step-wise algorithm of action is proposed and the
      diagnostic strength of the steps discussed. The key point is to select potential
      candidates to define the probability of an ongoing infection and then to select
      the tools to strengthen the suspicion. Further procedures are based on the
      analysis of the pseudo-synovial fluid obtained by aspiration. Diagnostic
      conclusions form the basis for treatment decisions.

PMID- 22956370
TI  - Preformed antibiotic-loaded cement spacers for two-stage revision of infected
      total hip arthroplasty. Long-term results.
AB  - Two-stage revision is the most widely accepted and performed intervention for
      chronically infected hip prosthesis and different interim spacers have been
      proposed. In recent years, antibiotic-loaded preformed spacers have become
      available on the market. The aim of this retrospective study was to assess the
      long-term results of two-stage revision with preformed spacers and uncemented hip
      prosthesis for the treatment of septic hip prosthesis. From 2000 to 2010, 183
      consecutive patients underwent two-stage revision of septic hip prosthesis, with
      a same protocol, including preformed antibiotic-loaded cement spacer and a
      cementless modular hip revision prosthesis and four to six weeks antibiotic
      administration. Clinical and radiologic assessment at a minimum follow-up of two
      years was performed. At a minimum two years follow-up, 10 patients (5.4%) had had
      an infection recurrence, four (2.2%) an aseptic loosening and four more required
      partial revision of the modular components of the prosthesis, because of hip
      instability/dislocation; 21 patients died or were lost to follow-up. Considering
      all the reasons for revision, survivorship at eleven years was 93.9%. Harris Hip
      Score improved from 29.1 +/- 14.6 pre-operatively to 41.1 +/- 15.9 after spacer
      implant and 81.7 +/- 17.6 after hip revision. The main complications after spacer
      implant included: spacer dislocation (16.4%), intra-operative femoral fractures
      (2.7%), and thromboembolism (2.1%). Complications after hip revision were:
      instability/dislocation (4,3%), intra-operative femoral fractures (1.6%), and
      thromboembolism (3.3%). Two-stage revision of septic hip prosthesis with
      preformed antibiotic-loaded spacers and cementless hip prosthesis provides
      satisfactory long-term results, with reduced complications.

PMID- 22956371
TI  - Bone grafting and two-stage revision total hip arthroplasty.
AB  - Periprosthetic deep infection in combination with substantial bone loss is one of
      the most challenging situations in revision hip surgery. We believe the effective
      management of these patients requires infection control as well as bone
      reconstruction. A review of our previously published studies on antibiotic loaded
      bone allografts is presented in this paper. These investigations provided us with
      information on the use of bone allografts in combination with antibiotics in
      cases of previous infection. Our protocol is based on removal of implants,
      meticulous debridement, parenteral antibiotic therapy and a second-stage
      reconstruction with vancomycin-supplemented bone allografts to treat an infected
      hip arthroplasty. We observed that vancomycin does not affect bone allograft
      incorporation at concentrations that are 300 times higher than the minimum
      inhibitory concentration for Staphylococcus aureus and Staphylococcus
      epidermidis. We also obtained adequate pharmacokinetics using these composites,
      with high local levels without renal impairment. This method has the capacity of
      acetabular and femoral bone stock restoration, with sound fixation and without
      increasing the rate of reinfection.

PMID- 22956372
TI  - Septic complications, although relatively rare, are still among the most frequent
      reasons for failure after hip replacement (the third reason for revision
      according to national registry data). Foreword.

PMID- 22956373
TI  - Diagnosis of periprosthetic joint infections.
AB  - Advances in implant design, surgical technique, peri-operative antimicrobial
      prophylaxis and laminar airflow operating room environment have made total joint
      arthroplasty one of the most successful surgical procedures of all times.
      Orthopaedic implants, however, remain prone to microbial contamination resulting
      in persistent risk of implant-associated infection. Treatment of infections
      associated with orthopaedic devices usually requires appropriate surgical
      intervention combined with a prolonged antimicrobial therapy. The choice of the
      best possible treatment regimen depends on duration and pathogenesis of
      infection, stability of the implant, antimicrobial susceptibility of the pathogen
      and condition of the surrounding soft tissue. In addition towell known diagnostic
      procedures new promising tools for rapid and correct microbial diagnosis are
      being developed as correct diagnosis of the responsible micro-organism and this
      is paramount for successful treatment of prosthetic joint infection.

PMID- 22956374
TI  - Retraction: "Outcome of short proximal femoral nail antirotation and dynamic hip
      screw for fixation of unstable trochanteric fractures. A randomised prospective
      comparative trial" [Hip Int 2011; 21(05): 531-6].

PMID- 22956376
TI  - Infection in periprosthetic hip fractures.
AB  - Fracture around the acetabulum and femur in total hip arthroplasty is a possible
      complication, sometimes with difficult surgical solution, namely when a sepsis is
      present. Periprosthetic hip fractures were classified according to a modified
      Vancouver classification. We treated 112 patients (67 men and 45 women) with
      periprosthetic hip fractures: 105 femoral fractures (94%) and seven acetabular
      fractures (6%). Mean follow-up was 10.6 years. For Type A (seven cases - 7%), B1
      (10 cases - 10%) or C (13 cases - 12%) fractures around well fixed femoral stems
      we only fixed the fractures. For Type B2 (17 cases - 16%), B3 (46 cases - 44%)
      and D (12 cases - 11%, with associated fractures, not contemplated in the
      Vancouver classification) we used an uncemented long femoral stem, fixation with
      metallic cables and cancellous bone allografts to fill the femoral bone loss. We
      observed a deep infection in three patients (2.7%), three early hip dislocations
      treated by closed reductions, two cases with asymptomatic trochanteric non-union
      and one femoral refracture. In the three infection cases we performed two-stage
      revision with cementless hip prosthesis, using an antibiotic-loaded cement hip
      spacer (three to eight months), a six weeks period of parenteral antibiotics and
      we performed articular aspiration before revision surgery. Until now, we did not
      observe any re-infection. It is very important to make an early diagnosis,
      isolate micro-organisms and ensure their antibiotic susceptibility. The surgery
      solution depends on the well fixed implants and periprosthetic osteolysis and
      articular instability.

PMID- 22956377
TI  - Incidence and outcome after infection of megaprostheses.
AB  - Recent advances in chemotherapy and radiation therapy in the treatment of
      malignant bone tumours as well as the consistent increase of revision
      arthroplasties have been followed by an increased use of megaprostheses. These
      large foreign bodies make infection a common and feared complication. Infection
      rates of 3 - 31% have been reported (average approx. 15%), often in conjunction
      with risk factors, e.g. the anatomic region (pelvis implants in particular),
      implant alloy, and underlying reason for implantation of a megaprosthesis. Apart
      from the basic principles of septic revision arthroplasty, special patient and
      implant factors have to be considered in infected megaprosthesis, which we have
      summarised in our paper (e.g. life expectancy, implant design, spacers and
      external stabilisation). This article further analyses the current literature
      available for these cases and summarises outcome after treatment of
      periprosthetic infections.

PMID- 22956378
TI  - A two stage re-implantation protocol for the treatment of deep periprosthetic hip
      infection. Mid to long-term results.
AB  - Deep periprosthetic hip infection is a devastating complication. Goal of
      treatment is infection eradication and durable functional reconstruction. Two
      stage re-implantation is the standard of treatment. From January 1998 to December
      2004 we treated 38 patients with an infected THA. There were 24 females and 14
      males, with a mean age of 67 years (61-75). The infection occurred 13 months to
      15 years (mean: 7.2 years) after the index operation. The mean follow-up was 11.6
      years (7 to 14). 35 patients were available for review. Almost one third of the
      patients had been treated before with antibiotics. In 5 cases more than one
      pathogen were present. In 3 cases, it was not possible to isolate a causative
      organism. In 15 cases (43%), a resistant pathogen was isolated. We used a two
      stage re- implantation protocol. Spacer was not used in any of the cases. Femoral
      revision was performed with uncemented implants, 21 of distal (wagner type)
      fixation and 14 of modular type with proximal fixation. 24 press fit shells (17
      oTMT cups) and 11 Muller rings were used. In 33 cases (94%) eradication of
      infection was achieved. The mean HHS improved from a mean of 38.2 preoperatively
      to a mean of 88.6 at final follow-up (p<0.001). There was no case of implant
      loosening or migration. Chronic late infection can be managed successfully with a
      two stage re-implantation protocol, without interim spacer, including neglected
      cases, previous long term antibiotics and cases with resistant pathogens.

PMID- 22956379
TI  - Definition of infection.
AB  - Acute periprosthetic infections occur either early, due to perioperative
      contamination, or late and haematogenous, and are caused by virulent bacteria.
      Late chronic or delayed periprosthetic infections produce implant loosening or
      symptoms of articular pain, and are caused by low-virulence bacteria. The
      intension of the definitions characterising the virulence of bacteria are more
      important than exact periods (delayed from 4 weeks to 2 years, early before and
      late after this period).

PMID- 22956380
TI  - Girdlestone procedure: when and why.
AB  - Girdlestone is one of the options for treating an infected hip arthroplasty
      (along with isolated antibiotics, debridement, and one or two-stage exchange).
      The choice must be based on a list of previous considerations. RESULTS OF
      GIRDLESTONE: Major differences among different series are reported in literature:
      from 13% to 83% of patients are satisfied with the result. Healing of infection
      is attained in 80% to 100% of patients, but figures are worse in special subsets
      (rheumatoid arthritis, enterococcal and methicillin-resistant infections, or when
      cement is retained). Pain is reported as severe in 16% to 33% of patients,
      moderate in 24% to 53% and mild in 76%, while only some authors refer to
      "satisfactory pain relief". Up to 45% of geriatric patients are unable to walk
      and only 29% walk independently. The literature reports Harris Hip scores from 25
      to 64. INDICATIONS FOR GIRDLESTONE: Absolute indications: non-ambulatory patients
      because of other problems or diseases, and impossible reimplantation (2nd-stage
      surgery) (unacceptable anaesthetic or surgical risk, technical difficulties,
      patient rejection). RELATIVE INDICATIONS: Dementia (risk of dislocation vs.
      severely reduced walking ability), immunocompromise (up to what degree of immune
      impairment do we accept to take the risk?), intravenous drug abuse (how can you
      prove it?).

PMID- 22956381
TI  - Value of debridement and irrigation for the treatment of peri-prosthetic
      infections. A systematic review.
AB  - Debridement and irrigation has been proposed as a salvage procedure for early
      post-operative and late acute haematogenous periprosthetic hip and knee
      infections, however the effective ability of this procedure to avoid recurrent
      infection is still debated. In this systematic review of the literature we
      reviewed full-text papers published from 1970 through 2011, that reported the
      success rate of infection eradication after debridement and irrigation with
      prosthesis retention for the treatment of early septic complications (within six
      weeks from surgery) or late acute haematogenous infections after hip or knee
      prosthesis. In all, 14 original articles, reporting the results of 710 patients
      were retrieved. The average success rate has been, respectively, 45.9% and 52%
      after a single or repeated debridement and irrigation procedures, at a mean
      follow-up of 53.3 months. The methodological limitations of this study and the
      heterogeneous material in the reviewed papers notwithstanding, this systematic
      review shows that debridement and irrigation procedure is associated with a
      rather poor outcome, even in a population of patients selected on the basis of
      symptoms' duration and patients should be adequately informed prior to undergo
      this salvage procedure.

PMID- 22956382
TI  - Peri-prosthetic infections. When to avoid surgery.
AB  - Successful treatment of prosthetic joint infections often requires multiple
      surgical interventions and prolonged antibiotic therapy. However, in some
      specific situations surgical intervention can not be the treatment of choice. We
      refer to situations where there is no pain or impairment of the general
      conditions, involving patients, usually elderly, refusing surgery. In these cases
      we consider the conservative approach as an option.

PMID- 22956383
TI  - The role of infection-associated risk factors in prosthetic surgery.
AB  - The number of obese people with diabetes mellitus (DM) is increasing. DM is in
      itself a risk factor for all types of infections, including infections after
      total hip and knee prosthetic surgery. In particular, the prevalence of obesity
      is high among orthopaedic patients. Obesity is also a risk factor for post
      operative infections in general. After total hip arthroplasty obese patients have
      a threefold increased risk for post-operative infections compared to a patient
      with normal weight. There is an association between DM and obesity, and this
      association is explained by the presence of metabolic syndrome. Fat tissue in
      people with abdominal obesity acts as an endocrine organ and metabolic syndrome
      is characterized by a condition of chronic inflammation, insulin resistance, and
      vascular obstructive disease. The obese patient with DM should be considered a
      high risk patient for post-operative infection in all types of surgery. Efforts
      should be made to identify patients with a metabolic syndrome prior to prosthetic
      surgery. Fasting glucose levels and HbA1C should be included in pre-operative
      blood tests, and, if necessary, specialists in internal medicine and
      endocrinology should assess the patient pre-operatively. The amount of
      antibiotics administered as prophylaxis should be adjusted to the body mass and
      the blood glucose level should be controlled per-operatively. Persistent wound
      drainage for more than five days post-operatively should be considered for
      surgical revision. If possible, the patient should of course lose weight before
      the operation, but the role of bariatric surgery is not discussed in this
      presentation.

PMID- 22956385
TI  - Bone grafting and one-stage revision of THR - biological reconstruction and
      effective antimicrobial treatment using antibiotic impregnated allograft bone.
AB  - Infection of a total hip replacement (THR) is considered one of the most serious
      complications in orthopaedic surgery. Problems derive from the presence of
      biofilms with inherent resistance to usual antibiotic treatment and bone defects
      resulting from infection induced osteolysis. Discussions on the choice of
      treatment mainly focus on the chance of eradicating the infection in either one
      or more stages. The advantages of only one operation with regard to patients'
      satisfaction, functional results and economical burden are evident. However, the
      fear of re-infection usually leads surgeons to multiple stage procedures, mostly
      using antibiotic loaded spacers in the interval. Spacers have no effect on
      biofilms and are associated with a high rate of complications such as breakage or
      dislocation. Cemented revisions show several disadvantages like reduction of
      biomechanical properties through added antibiotics, inferior long term results,
      difficulties of removal in case of recurrence etc. Uncemented implants appear
      more advantageous but are at risk of becoming colonised by remaining biofilm
      fragments. To overcome this risk higher local concentrations of antibiotics are
      needed. Allograft bone may be impregnated with high loads of antibiotics using
      special incubation techniques, resulting in an antibiotic bone compound (ABC).
      ABC provides local concentrations exceeding those of cement by more than a 100
      fold and efficient release is prolonged for several weeks. At the same time it is
      likely to restore bone stock, which is usually compromised after removal of an
      infected endoprosthesis. Based on these considerations new protocols for one
      stage exchange of infected THR have been established. Bone voids may be filled
      with ABC, uncemented implants may be fixed in original healthy bone. Recent
      studies indicate an overall success rate of more than 90% with one operation,
      without any adverse side effects. Incorporation of allografts appears as after
      grafting with unimpregnated bone grafts. One stage revision using ABC together
      with uncemented implants, should be at least comparable to multiple stage
      procedures, but with the advantage of the obvious benefits for patients and cost.

PMID- 22956386
TI  - Peri-prosthetic hip infections: in favour of one-stage.
AB  - Although it does offer certain obvious advantages, the one-staged revision
      approach in infected THA remains rare in the field of orthopaedics. Besides the
      reduced number of surgical interventions for patients, it is associated with a
      decreased inpatient hospital stay and quicker mobilisation. Furthermore, it might
      be the more cost-effective approach and enables a reduced duration of post
      operative systemic antibiotics, usually less than 14 days in our setting.
      Technically speaking, the presence of a positive culture of a pre-operative
      aspiration and respective antibiogram are mandatory requirements. A general
      cemented implant fixation using topical antibiotics is the treatment of choice
      for single-staged procedures. The key to surgical success is based on the well
      defined and detailed intra-hospital infrastructure, including a meticulous pre
      operative hip aspiration regime, pre-operative planning and an aggressive intra
      operative surgical approach.

PMID- 22956387
TI  - Hip International in 2012.

PMID- 22956388
TI  - Determinants of health-related quality of life after aneurysmal subarachnoid
      hemorrhage: a systematic review.
AB  - BACKGROUND AND PURPOSE: Many persons with subarachnoid hemorrhage (SAH) from a
      ruptured intracranial aneurysm recover to functional independence but
      nevertheless experience reduced quality of life (QoL). The aim of this study was
      to summarize the evidence on determinants of reduced QoL in this diagnostic
      group. METHODS: Databases PubMed, PsychINFO, and CINAHL were used to identify
      empirical studies reporting on quantitative relationships between possible
      determinants and QoL in persons with aneurysmal SAH and published in English.
      Determinants were classified using the International Classification of
      Functioning, Disability and Health (ICF). RESULTS: Twenty studies met the
      inclusion criteria for this review, in which 13 different HRQoL questionnaires
      were used. Determinants related to Body Structure & Function (clinical condition
      at admission, fatigue, and disturbed mood), Activity limitations (physical
      disability and cognitive complaints), and Personal factors (female gender, higher
      age, neuroticism, and passive coping) are consistently related to worse HRQoL
      after aneurysmal SAH. Treatment characteristics were not consistently related to
      HRQoL. CONCLUSION: This study identified a broad range of determinants of HRQoL
      after aneurysmal SAH. The findings provide clues to tailor multidisciplinary
      rehabilitation programs. Further research is needed on participation,
      psychological characteristics, and environmental factors as determinants of HRQoL
      after SAH.

PMID- 22956389
TI  - Moderate red wine and grape juice consumption modulates the hydrolysis of the
      adenine nucleotides and decreases platelet aggregation in streptozotocin-induced
      diabetic rats.
AB  - This study investigated the ex vivo effects of the moderate red wine (RW) and
      grape juice (GJ) consumption, and the in vitro effects of the resveratrol,
      caffeic acid, gallic acid, quercetin, and rutin on NTPDase (nucleoside
      triphosphate diphosphohydrolase), ecto-nucleotide
      pyrophosphatase/phosphodiesterase (E-NPP), 5'-nucleotidase, and adenosine
      deaminase (ADA) activities in platelets and platelet aggregation from
      streptozotocin-induced diabetic rats. The animals were divided into six groups (n
      = 10): control/saline, control/GJ, control/RW, diabetic/saline, diabetic/GJ, and
      diabetic/RW. RW and GJ were administered for 45 days; after this period, the
      blood was collected for experimental determinations. Results showed that NTPDase,
      E-NPP, 5'-nucleotidase, and ADA activities as well as platelet aggregation were
      increased in the diabetic/saline group compared to the control/saline group.
      Treatment with RW and GJ increased ectonucleotidases activities and prevented the
      increase in the ADA activity in the diabetic/GJ and diabetic/RW groups. Platelet
      aggregation was also decreased by the treatment with RW and GJ in the diabetic/GJ
      and diabetic/RW groups. In the in vitro tests, resveratrol, caffeic acid, and
      gallic acid increased ATP, ADP, and AMP hydrolysis, while quercetin and rutin
      decreased the hydrolysis of these nucleotides in platelets of diabetic rats. The
      ADA activity and platelet aggregation were reduced in platelets of diabetic rats
      in the presence of all polyphenols tested in vitro. These findings suggest that
      RW, GJ, and all polyphenols tested were able to modulate the ectoenzymes
      activities. Moreover, a decrease in the platelet aggregation was observed and it
      could contribute to the prevention of platelet abnormality, and consequently
      vascular complications in diabetic state.

PMID- 22956391
TI  - Role of nuclear factor-KB in breast and colorectal cancer.
AB  - The purpose of this review article is to highlight articles and new research
      regarding the link between NF-KB and several cancers. This review presents the
      most up-to-date NF-KB research and how it links this important transcription
      factor with hematology and oncology. It was written by conducting a thorough
      search of Pubmed as well as several journals such as Cancer, Nature, Science,
      Cell and those of one of the authors. The articles relating to the link between
      NF-KB and cancer were used to write this review. The results of this study
      clarified that there is a critical link between NF-KB and cancer. NF-KB has often
      been implicated in a variety of different diseases and it plays a variety of
      roles in cell survival, differentiation, and proliferation of cells. In cancer,
      NF-KB plays a pivotal role by facilitating oncogenesis as well as metastasis. A
      thorough understanding of NF-KB and its role in cancer can lead to future studies
      and drug development which could provide a novel option in the treatment of this
      disease.

PMID- 22956390
TI  - An update on stem cell transplantation in autoimmune rheumatologic disorders.
AB  - Stem cell transplant (SCT) has long been the standard of care for several
      hematologic, immunodeficient, and oncologic disorders. Recently, SCT has become
      an increasingly utilized therapy for refractory autoimmune rheumatologic
      disorders (ARDs). The efficacy of SCT in ARDs has been attributed to resetting an
      aberrant immune system either through direct immune replacement with
      hematopoietic stem cells or through immunomodulation with mesenchymal stem cells.
      Among ARDs, refractory systemic sclerosis (SSc) and systemic lupus erythematosus
      (SLE) are the most common indications for SCT. SCT has also been used in
      refractory rheumatoid arthritis, inflammatory myopathies, antiphospholipid
      syndrome, granulomatosis with polyangiitis, and pediatric ARDs. Complete
      responses have been reported in approximately 30 % of patients in all disease
      categories. Transplant-related mortality, however, remains a concern. Future
      large multi-center prospective randomized clinical trials will help to better
      define the specific role of SCT in the treatment of patients with ARDs.

PMID- 22956392
TI  - H5N1 highly pathogenic avian influenza in Indonesia: retrospective
      considerations.
AB  - Indonesia is one of the five countries where highly pathogenic avian influenza
      viruses of the H5N1 subtype (H5N1 HPAI) remain endemic in poultry. Importantly,
      it is one of the countries where the virus causes human infections. WHO data
      indicate that as of 2 May 2012, 189 human cases of Influenza A (H5N1) had been
      reported in Indonesia, with 157 human deaths. These human cases included a small
      number in which limited human-to-human transmission could have occurred. Hence,
      there remains a critical need in Indonesia for a more effective One Health
      approach to the control and prevention of this disease in people and in poultry.
      This chapter explores a number of aspects of the evolution of this disease in
      Indonesia, the virus that causes it and the control and preventive measures
      introduced, focusing on the successes and shortcomings of veterinary and One
      Health approaches. Indonesia provides many examples of situations where this
      latter approach has been successful, and others where further work is needed to
      maximize the benefits from coordinated responses to this disease leading to
      effective management of the risk to human health. 

PMID- 22956393
TI  - The past tense inflection project (PTIP): speeded past tense inflections,
      imageability ratings, and past tense consistency measures for 2,200 verbs.
AB  - The processes involved in past tense verb generation have been central to models
      of inflectional morphology. However, the empirical support for such models has
      often been based on studies of accuracy in past tense verb formation on a
      relatively small set of items. We present the first large-scale study of past
      tense inflection (the Past Tense Inflection Project, or PTIP) that affords
      response time, accuracy, and error analyses in the generation of the past tense
      form from the present tense form for over 2,000 verbs. In addition to standard
      lexical variables (such as word frequency, length, and orthographic and
      phonological neighborhood), we have also developed new measures of past tense
      neighborhood consistency and verb imageability for these stimuli, and via
      regression analyses we demonstrate the utility of these new measures in
      predicting past tense verb generation. The PTIP can be used to further evaluate
      existing models, to provide well controlled stimuli for new studies, and to
      uncover novel theoretical principles in past tense morphology.

PMID- 22956394
TI  - The influence of calibration method and eye physiology on eyetracking data
      quality.
AB  - Recording eye movement data with high quality is often a prerequisite for
      producing valid and replicable results and for drawing well-founded conclusions
      about the oculomotor system. Today, many aspects of data quality are often
      informally discussed among researchers but are very seldom measured, quantified,
      and reported. Here we systematically investigated how the calibration method,
      aspects of participants' eye physiologies, the influences of recording time and
      gaze direction, and the experience of operators affect the quality of data
      recorded with a common tower-mounted, video-based eyetracker. We quantified
      accuracy, precision, and the amount of valid data, and found an increase in data
      quality when the participant indicated that he or she was looking at a
      calibration target, as compared to leaving this decision to the operator or the
      eyetracker software. Moreover, our results provide statistical evidence of how
      factors such as glasses, contact lenses, eye color, eyelashes, and mascara
      influence data quality. This method and the results provide eye movement
      researchers with an understanding of what is required to record high-quality
      data, as well as providing manufacturers with the knowledge to build better
      eyetrackers.

PMID- 22956395
TI  - Dynamic visuomotor synchronization: quantification of predictive timing.
AB  - When a moving target is tracked visually, spatial and temporal predictions are
      used to circumvent the neural delay required for the visuomotor processing. In
      particular, the internally generated predictions must be synchronized with the
      external stimulus during continuous tracking. We examined the utility of a
      circular visual-tracking paradigm for assessment of predictive timing, using
      normal human subjects. Disruptions of gaze-target synchronization were associated
      with anticipatory saccades that caused the gaze to be temporarily ahead of the
      target along the circular trajectory. These anticipatory saccades indicated
      preserved spatial prediction but suggested impaired predictive timing. We
      quantified gaze-target synchronization with several indices, whose distributions
      across subjects were such that instances of extremely poor performance were
      identifiable outside the margin of error determined by test-retest measures.
      Because predictive timing is an important element of attention functioning, the
      visual-tracking paradigm and dynamic synchronization indices described here may
      be useful for attention assessment.

PMID- 22956397
TI  - Telephone-delivered motivational interviewing targeting sexual risk behavior
      reduces depression, anxiety, and stress in HIV-positive older adults.
AB  - BACKGROUND: Few studies have examined the secondary benefits of HIV risk
      reduction interventions to improve mental health functioning. PURPOSE: This study
      aimed to examine the effectiveness of telephone-delivered motivational
      interviewing (MI) targeting sexual risk behavior to reduce depression, anxiety,
      and stress in HIV-positive older adults. METHODS: Participants were 100 HIV
      positive adults 45+ years old enrolled in a sexual risk reduction pilot clinical
      trial of telephone-delivered MI. Participants were randomly assigned to a one
      session MI, four-session MI, or standard of care control condition. Telephone
      interviews at baseline and 3- and 6-month follow-up assessed sexual behavior,
      depression, anxiety, and stress. RESULTS: Relative to controls, participants in
      the one- and four-session MI conditions reported lower levels of depression,
      anxiety, and stress at 6-month follow-up. No between group differences were
      observed at 3-month follow-up or between one- and four-session MI participants at
      6-month follow-up. CONCLUSIONS: Preliminary data suggest that telephone-delivered
      MI to reduce sexual risk behavior may confer secondary benefits of improving
      mental health functioning in HIV-positive persons.

PMID- 22956396
TI  - Progesterone receptor (PR) variants exist in breast cancer cells characterised as
      PR negative.
AB  - Progesterone receptor (PR) expression is measured in breast cancer by
      immunohistochemistry using N-terminally targeted antibodies and serves as a
      biomarker for endocrine therapeutic decisions. Extensive PR alternative splicing
      has been reported which may generate truncated PR variant proteins which are not
      detected by current breast cancer screening or may alter the function of proteins
      detected in screening. However, the existence of such truncated PR variants
      remains controversial. We have characterised PR protein expression in breast
      cancer cell lines using commercial PR antibodies targeting different epitopes.
      Truncated PR proteins are detected in reportedly PR negative MDA-MB-231 cells
      using a C-terminally targeted antibody. Antibody specificity was confirmed by
      immunoblotting following siRNA knockdown of PR expression. We have further
      demonstrated that alternatively spliced PR mRNA is present in MDA-MB-231 cells
      and in reportedly PR-negative breast tumour tissue which could encode the
      truncated PR proteins detected by the C-terminal antibody. The potential function
      of PR variant proteins present in MDA-MB-231 cells was also assessed, indicating
      the ability of these PR variants to bind progesterone, interact with a nuclear PR
      co-factor and bind DNA. These findings suggest that alternative splicing may
      generate functional truncated PR variant proteins which are not detected by
      breast cancer screening using N-terminally targeted antibodies leading to
      misclassification as PR negative.

PMID- 22956398
TI  - The influence of instrument configuration on tissue handling force in
      laparoscopy.
AB  - In single-access surgery, instruments enter the abdominal cavity through only 1
      incision, the position of the instruments relative to each other is different
      compared with that in conventional laparoscopy. Changes in instrument
      configuration may increase task complexity and therefore affect tissue handling
      skills. The aim of this study is to determine if a relation exists between
      instrument configuration and tissue interaction force. A study was performed to
      investigate the differences in manipulation force between a single-port (SP) and
      2-port (TP) instrument configuration in a standard box trainer. A force platform
      was placed under a tissue manipulation task in a box trainer and used to measure
      the pulling forces and trial time. A total of 28 medical students with no
      previous experience in laparoscopic surgery were divided into 2 equal groups.
      Group 1 trained the task 6 times with the TP configuration and subsequently
      performed 6 trials with the SP configuration. Group 2 used the configurations in
      the opposite order. For both groups, the learning curves of the maximum force and
      task time were compared. Time and maximum pulling forces were significantly
      different between the 2 instrument configurations. In both groups, the
      participants used significantly more force in the SP configuration than in the TP
      configuration. The force data indicate that the increased complexity in
      instrument handling with straight instruments in a SP configuration increases the
      tissue manipulation force. Furthermore, the tissue handling skills of novices who
      mastered the task with the TP configuration decreased after switching to the SP
      configuration.

PMID- 22956399
TI  - Enhancing fundamental robot-assisted surgical proficiency by using a portable
      virtual simulator.
AB  - BACKGROUND: The development of a virtual reality (VR) training platform provides
      an affordable interface. The learning effect of VR and the capability of skill
      transfer from the VR environment to clinical tasks require more investigation.
      METHODS: Here, 14 medical students performed 2 fundamental surgical tasks
      bimanual carrying (BC) and peg transfer (PT)-in actual and virtual environments.
      Participants in the VR group received VR training, whereas participants in the
      control group played a 3D game. The learning effect was examined by comparing
      kinematics between pretraining and posttraining in the da Vinci Surgical System.
      Differences between VR and playing the 3D game were also examined. RESULTS: Those
      who were trained with the VR simulator had significantly better performance in
      both actual PT (P = .002) and BC (P < .001) tasks. The time to task completion
      and the total distance traveled were significantly decreased in both surgical
      tasks in the VR group compared with the 3D game group. However, playing the 3D
      game showed no significant enhancement of fundamental surgical skills in the
      actual PT task. The difference between pretraining and posttraining was
      significantly larger in the VR group than in the 3D game group in both the time
      to task completion (P = .002) and the total distance traveled (P = .027) for the
      actual PT task. Participants who played the 3D game seemed to perform even worse
      in posttraining. CONCLUSIONS: Training with the portable VR simulator improved
      robot-assisted surgical skill proficiency in comparison to playing a 3D game.

PMID- 22956400
TI  - Feasibility of transumbilical flexible endoscopic preperitoneoscopy (FLEPP) and
      its utility for inguinal hernia repair: experimental animal study.
AB  - BACKGROUND AND STUDY AIMS: Various NOTES (natural orifice translumenal endoscopic
      surgery) hernia repair techniques have been described. The aim of this study was
      to evaluate the feasibility of a transumibilically introduced conventional double
      channel flexible endoscope for performing preperitoneoscopy (FLEPP, flexible
      endoscopic preperitoneoscopy technique) and to perform totally extraperitoneal
      (TEP) inguinal hernia meshplasty in an animal model. MATERIAL AND METHODS: The
      study was done in 2 steps on 8 swines weighing 25 to 30 kg each: (1) establishing
      feasibility of preperitoneal dissection of the inguinal region using a
      conventional double-channel flexible gastroscope and making bed for mesh
      placement and (2) placement of a polypropylene mesh in the inguinal region to
      cover the myopectineal orifice. RESULTS: The flexible endoscope provided good
      vision and maneuverability to identify preperitoneal structures--namely, the
      arcuate line, insertion of rectus abdominis on pubis symphysis, inferior
      epigastric vessels, deep inguinal ring, spermatic cord, pubic symphysis, and
      psoas muscle--without causing any damage to any of the structures. The spermatic
      cord could be dissected to identify the vas deference. A 9 * 7 cm(2) oval mesh
      was successfully placed over the myopectineal orifice of Fruchaud with good
      overlap. Average time required for the complete FLEPP procedure (including mesh
      placement) was 55 minutes (range 45-90 minutes). CONCLUSIONS: This study
      demonstrates, for the first time, the feasibility of the transumbilical FLEPP
      technique and its utility for performing TEP inguinal hernia repair with
      prosthetic mesh placement in a swine model.

PMID- 22956401
TI  - Surgical options in lumbar hernia: laparoscopic versus open repair. A long-term
      prospective study.
AB  - OBJECTIVE: To determine the safety and effectiveness of laparoscopic lumbar
      hernia repair. DESIGN: Prospective clinical study. SETTING: Abdominal wall unit,
      university hospital. PATIENTS: Between January 1995 and December 2008, data from
      55 consecutive patients who had undergone laparoscopic (n = 35) or open (n = 20)
      lumbar hernia repair. MAIN OUTCOME MEASURES: The primary endpoint was recurrence;
      secondary endpoints were patient outcomes (morbidity, pain, and return to normal
      activity). RESULTS: Mean operating time (P = .01), hospital stay, return to
      normal activity, analgesic consumption, and pain at 1 month (P < .001) were
      significantly less in the laparoscopic group. Complications were similar in the 2
      groups (37% vs 40%, respectively; P = .50). Traumatic hernias increased local
      complications versus incisional lumbar hernias (71.4% vs 29%; P = .007).
      Consumption of analgesics (6.8 +/- 6.5 vs 18.1 +/- 9.1; P < .001) and pain during
      the first month (no pain: 90% vs 54.3%; P = .015) were significantly less with a
      lightweight versus medium-weight mesh. The risk factors associated with
      recurrences development were localization (P = .01) and size (P = .008).
      Recurrence rates were 2.9% in the laparoscopic group and 15% in the open group (P
      = .13). CONCLUSIONS: Outcomes did not differ with respect to morbidity and
      recurrence rate after long-term follow-up; however, this study suggested that
      laparoscopic approach for lumbar hernia is safe, effective, and more efficient
      than open repair and can be considered the procedure of choice. Open surgery may
      be considered the best option in the diffuse hernias with size larger than 15 cm.

PMID- 22956402
TI  - Maternal and fetal outcomes after introduction of magnesium sulphate for
      treatment of preeclampsia and eclampsia in selected secondary facilities: a low
      cost intervention.
AB  - The aim of this study was to evaluate whether a new low-cost strategy for the
      introduction of magnesium sulphate (MgSO4) for preeclampsia and eclampsia in low
      resource areas will result in improved maternal and perinatal outcomes. Doctors
      and midwives from ten hospitals in Kano, Nigeria, were trained on the use of
      MgSO4. The trained health workers later conducted step-down training at their
      health facilities. MgSO4, treatment protocol, patella hammer, and calcium
      gluconate were then supplied to the hospitals. Data was collected through
      structured data forms. The data was analyzed using SPSS software. From February
      2008 to January 2009, 1,045 patients with severe preeclampsia and eclampsia were
      treated. The case fatality rate for severe preeclampsia and eclampsia fell from
      20.9 % (95 % CI 18.7-23.2) to 2.3 % (95 % CI 1.5-3.5). The perinatal mortality
      rate was 12.3 % as compared to 35.3 % in a center using diazepam. Introduction of
      MgSO4 in low-resource settings led to improved maternal and fetal outcomes in
      patients presenting with severe pre-eclampsia and eclampsia. Training of health
      workers on updated evidence-based interventions and providing an enabling
      environment for their practice are important components to the attainment of the
      Millennium Development Goals (MDG) in developing countries.

PMID- 22956403
TI  - Greater complexity of liver surgery is not associated with an increased incidence
      of liver-related complications except for bile leak: an experience with 2,628
      consecutive resections.
AB  - BACKGROUND: Advances in technique, technology, and perioperative care have
      allowed for the more frequent performance of complex and extended hepatic
      resections. The purpose of this study was to determine if this increasing
      complexity has been accompanied by a rise in liver-related complications.
      METHODS: A large prospective single-institution database of patients who
      underwent hepatic resection was used to identify the incidence of liver-related
      complications. Liver resections were divided into an early era and a late era
      with equal number of patients (surgery performed before or after 18 May 2006).
      Patient characteristics and perioperative factors were compared between the two
      groups. RESULTS: Between 1997 and 2011, 2,628 hepatic resections were performed,
      with a 90-day morbidity and mortality rate of 37 and 2 %, respectively. We
      identified higher rates of repeat hepatectomy (12.2 vs 6.1 %; p < 0.001), two
      stage resection (4.0 vs 1 %; p < 0.001), extended right hepatectomy (17.6 vs 14.6
      %; p = 0.04), and preoperative portal vein embolization (9.1 vs 5.9 %; p < 0.001)
      in the late era. The incidence of perihepatic abscess (3.7 vs 2.1 %; p = 0.02)
      and hemorrhage (0.9 vs 0.3 %; p = 0.045) decreased in the late era and the
      incidence of hepatic insufficiency (3.1 vs 2.6 %; p = 0.41) remained stable. In
      contrast, the rate of bile leak increased (5.9 vs 3.7 %; p = 0.011). Independent
      predictors of bile leak included bile duct resection, extended hepatectomy,
      repeat hepatectomy, en bloc diaphragmatic resection, and intraoperative
      transfusion. CONCLUSIONS: The complexity of liver surgery has increased over
      time, with a concomitant increase in bile leak rate. Given the strong association
      between bile leak and other poor outcomes, the development of novel technical
      strategies to reduce bile leaks is indicated.

PMID- 22956404
TI  - Long-term effects of gastric stimulation on gastric electrical physiology.
AB  - INTRODUCTION: This study evaluates the modeling of gastric electrophysiology
      tracings during long-term gastric electrical stimulation for gastroparesis. We
      hypothesized that serosal electrogastrogram may change over time representing
      gastric remodeling from gastric stimulation. PATIENTS: Sixty-five patients with
      gastroparesis underwent placement of gastric stimulator for refractory symptoms.
      Mean age at initial stimulator placement was 44 years (range, 8-76), current mean
      age was 49, and the majority of the subjects were female (n = 51, 78 %). Only a
      minority had diabetes-induced gastroparesis (n = 16, 25 %); the remainder were
      either idiopathic or postsurgical. METHODS: At the time of stimulator placement,
      electrogastrogram was performed after the gastric leads were placed but before
      stimulation was begun. Patients underwent continuous stimulation until pacer
      batteries depleted. At the time of replacement, before the new pacemaker was
      attached, electrogastrogram was again performed. RESULTS: After a mean of 3.9
      years of stimulation therapy, the mean of baseline frequency before stimulation
      therapy was 5.06 cycles/min and declined to 3.66 after replacement (p =
      0.0000002). The mean amplitude was 0.33 mV before stimulation therapy and
      decreased to 0.31 mV (p = 0.73). The frequency/amplitude ratio was 38.4 before
      stimulation therapy and decreased to 21.9 (p = 0.001). CONCLUSION: Long-term
      gastric electrical stimulation causes improvement in basal unstimulated gastric
      frequency to near normal.

PMID- 22956405
TI  - Ergonomics in laparoendoscopic single-site surgery: survey results.
AB  - BACKGROUND: Ergonomic issues are frequently reported by surgeons performing
      laparoendoscopic single-site (LESS) surgery. However, few studies have analysed
      this issue. METHODS: We used a web format survey to evaluate the opinion of
      surgeons with experience in this laparoscopic technique. This survey collected
      demographic information, surgical experience, physical and psychological
      symptoms, and technical problems related to this type of surgery. RESULTS: Some
      78 surgeons filled out the questionnaire. All participants had clinical
      experience in this type of laparoscopic approach, and 68 % had performed more
      than 30 procedures. Two or more musculoskeletal symptoms were reported during or
      after performing LESS surgery by 81 % of all surgeons. Surgeons with more
      experience in this approach reported fewer symptoms and technical difficulties.
      CONCLUSIONS: LESS surgery is accompanied by musculoskeletal problems and
      technical difficulties for surgeons. Technological advancements and greater
      surgical experience in the technique will alleviate these issues. More in-depth
      ergonomic studies are needed.

PMID- 22956406
TI  - 2012 SNM Highlights Lectures.

PMID- 22956408
TI  - Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous
      immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic
      purpura.
AB  - This study aimed to evaluate the efficacy, cost, and effects of anti-D
      immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin
      (IVIG) therapy on the development of chronic disease in children who are Rh
      positive with diagnosed immune thrombocytopenic purpura (ITP). Children with
      newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively
      randomized to treatment with anti-D Ig (50 MUg/kg), methylprednisolone (2
      mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7
      years were divided into three equal groups. No difference was observed between
      platelet counts before treatment and on day 3 of treatment. However, platelet
      counts at day 7 were lower in the methylprednisolone group than in the IVIG group
      (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were
      significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in
      30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the
      IVIG group, but no significant difference was noted among the groups. The cost
      analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig
      and 10.9 times higher than methylprednisolone. In the treatment of ITP in
      childhood, one 50 MUg/kg dose of anti-D Ig has similar effects to IVIG and
      methylprednisolone. Among patients who were treated with anti-D Ig, serious
      anemia was not observed, and the cost of treatment was less than that of IVIG
      treatment.

PMID- 22956409
TI  - Percutaneous coronary intervention in patients with haemophilia presenting with
      acute coronary syndrome: an interventional dilemma: case series, review of the
      literature, and tips for management.
AB  - Since the introduction of clotting factor concentrates over 50 years ago the life
      expectancy of patients with hemophilia (PWH) has increased to over 70 years.
      Consequently, diseases of the ageing population, including coronary artery
      disease, are increasingly being encountered. These patients present a unique
      therapeutic problem due to their greatly increased bleeding risk. Randomized
      controlled studies specific to PWH are lacking, emphasizing the need for case
      series. We present three cases of acute coronary syndrome in PWH who underwent
      urgent percutaneous coronary intervention at our institution, and summarize the
      available literature on the topic. We describe their management and outcome and
      provide points to consider when treating these complex patients.

PMID- 22956410
TI  - On the 'Diagnostic values of serum hCG on the outcome of pregnancy of unknown
      location (PUL): a systematic review and meta-analysis'.

PMID- 22956411
TI  - Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: a
      systematic review and meta-analysis.
AB  - BACKGROUND The term 'pregnancy of unknown location' (PUL) refers to cases where a
      pregnancy test is positive but the pregnancy cannot be visualized by transvaginal
      sonography (TVS). Various strategies integrating TVS and serum hCG measures are
      used to follow-up until the location and/or viability of the pregnancy becomes
      clear; however, the optimal strategy to predict the outcome of pregnancy in women
      with PUL is unknown. Therefore, we performed a systematic review and meta
      analysis to determine the diagnostic accuracy of the various serum hCG strategies
      in women with PUL.  METHODS We searched Medline and EMBASE for articles which
      were published (in any language) from 1980 to January 2012 on strategies using
      serum hCG in women with PUL and reporting on the final outcome of pregnancy. 
      RESULTS From 980 selected titles, 23 articles, all cohort studies, were included.
      There were 10 studies on a single serum hCG cut-off level, 4 on serum hCG ratio
      (hCG 48 h/hCG 0 h) and 6 on logistic regression modelling. Three other strategies
      were reported using serum hCG, serum progesterone and/or uterine curettage
      findings; each of these strategies comprised a single study. Comparative
      diagnostic studies have not been performed on the diagnostic value of serum hCG
      in women with PUL. Included studies showed substantial clinical heterogeneity in
      the definition of the outcome, and only data for the pregnancy outcome ectopic
      pregnancy (EP) were suitable for meta-analysis. The receiver operating
      characteristic curves showed that the serum hCG ratios and logistic regression
      models had a better performance as compared with an absolute single serum hCG
      level (as the curve was considerably closer to the diagonal, indicating no
      diagnostic value).  CONCLUSIONS Overall the study was limited by the high
      clinical heterogeneity of the data but in women with PUL diagnostic strategies
      using serum hCG ratios, either alone or in logistic regression models, have the
      best diagnostic performance in the case of EP. Well defined prospective
      comparative studies using standardized diagnostics and clinical application plus
      agreed definitions of outcome are required to identify the best strategy to
      diagnose pregnancy outcome in women with PUL.

PMID- 22956412
TI  - Metformin versus clomiphene citrate for infertility in non-obese women with
      polycystic ovary syndrome: a systematic review and meta-analysis.
AB  - BACKGROUND Recent studies suggest that metformin may be more effective in women
      with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to
      determine and compare the effectiveness of metformin and clomiphene citrate for
      improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32
      kg/m(2) was used to allow for international differences in BMI values which
      determine access to infertility therapy through the public health system). 
      METHODS Databases were searched for English language articles until July 2011.
      INCLUSION CRITERIA: women of any age, ethnicity and weight with PCOS diagnosed by
      all current criteria, who are infertile; at least 1000 mg of any type of
      metformin at any frequency, including slow release and standard release, compared
      with any type, dose and frequency of clomiphene citrate. OUTCOMES: rates of
      ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse
      events, quality of life and cost effectiveness. Data were extracted and risk of
      bias assessed. A random effects model was used for meta-analyses of data, using
      risk ratios (relative risk).  RESULTS The search returned 4981 articles, 580
      articles addressed metformin or clomiphene citrate and four randomized controlled
      trials (RCTs) comparing metformin with clomiphene citrate were included. Upon
      meta-analysis of the four RCTs, we were unable to detect a statistically
      significant difference between the two interventions for any outcome in women
      with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the
      RCTs.  CONCLUSIONS Owing to conflicting findings and heterogeneity across the
      included RCTs, there is insufficient evidence to establish a difference between
      metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth,
      miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32
      kg/m(2). However, a lack of superiority of one treatment is not evidence for
      equivalence, and further methodologically rigorous trials are required to
      determine whether there is a difference in effectiveness between metformin and
      placebo (or no treatment) or between metformin and clomiphene citrate for
      ovulation induction in women with PCOS who are non-obese. Until then, caution
      should be exercised when prescribing metformin as first line pharmacological
      therapy in this group of women.

PMID- 22956413
TI  - The effects of sonographic and demographic features and needle size on obtaining
      adequate cytological material in sonography-guided fine-needle aspiration biopsy
      of thyroid nodules.
AB  - The aim of this study is to investigate the effects of the sonographic
      characteristics of the nodule, demographic features of patient, and nodule size
      and needle size used for sampling, on obtaining adequate cytological material
      (CM) in thyroid fine-needle aspiration biopsy (FNAB). We performed 270 FNAB
      between September 2010 and June 2012. Size, echogenicity, and localization of all
      nodules were evaluated by ultrasonography (US) before the biopsy. Nodules were
      grouped as <1, 1-3, and >3 cm according to their size and as hypoechoic,
      isoechoic, hyperechoic, or heterogeneous according to their US characteristics.
      20-, 22-, and 24-G needles were used for the biopsies. Different sonographic
      characteristics of the nodules did not affect the needle selection. All specimens
      were classified as adequate or inadequate CM by a cytopathologist. A total of 270
      nodules were biopsied, 184 (68.1 %) specimens were considered as adequate CM and
      86 (31.9 %) specimens were considered as inadequate CM. Patient age and the
      presence of heterogeneous echogenicity were found to have prognostic significance
      in univariate analysis (p < 0.05). In a multivariate logistic regression model
      with forward stepwise method, advanced age (p = 0.001, OR = 1.042, 95CI 1.018
      1.068) and heterogeneous echogenicity (p = 0.017, OR = 1.955, 95CI 1.129-3.385)
      remained associated with an increased risk of inadequate CM obtainment after
      adjustment for other potential confounders (nodule size >3 cm and needle size 20
      G usage) and variables found to be statistically significant in univariate
      analysis. Non-diagnostic FNAB remains a significant problem in the evaluation of
      thyroid nodules and can be as high as 30 %. Inadequate CM rates for elderly
      patients and heterogeneous nodules were significantly higher than that for other
      factors. The nodule size and needle size used for sampling did not affect the
      adequacy of FNAB.

PMID- 22956415
TI  - Moving across boundaries: migration in South Africa, 1950-2000.
AB  - Existing knowledge about historical patterns of black internal migration in South
      Africa is incomplete, primarily because of the lack of good life course studies
      as well as the apartheid government's suppression and censoring of data. This
      article provides a comprehensive picture of historical internal migration
      patterns with an analysis of a unique individual retrospective life history data
      set. This sample of the black population, collected in 2000, is the only known
      nationally representative life history data for South Africa; it includes all
      residential moves for each individual during his/her lifetime. Various mobility
      outcomes are analyzed: moves within/across provinces, moves within/across rural
      and urban areas, forced moves, moves with a nuclear family, and individual moves.
      The results indicate that migration significantly increased among black South
      Africans during the last half of the twentieth century, and that this increase
      began before the Pass Laws were repealed in 1986 and well before the official end
      of apartheid in 1991 or the first free election in 1994. The timing of this
      increase in migration rates suggests that migration in defiance of the Pass Laws
      (albeit a dangerous and desperate proposition) was a way of life for many black
      South Africans.

PMID- 22956414
TI  - Evolving concepts of oxidative stress and reactive oxygen species in
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) continues to be a substantial health-care burden,
      despite recent treatment advances. Oxidative stress has long been regarded as a
      key pathophysiological mediator that ultimately leads to CVD including
      atherosclerosis, hypertension and heart failure. Over the past decade, emerging
      evidence has shifted our understanding of reactive oxygen species (ROS) from its
      harmful role to being signaling molecules. Here, we reviewed recent advances in
      our understanding of ROS that mediate the complex process of CVDs, with a focus
      on major ROS signaling and sources such as mitochondria and Nicotinamide Adenine
      Dinucleotide Phosphate (NADPH) oxidases.

PMID- 22956416
TI  - A survey experiment of women's attitudes about intimate partner violence against
      women in rural Bangladesh.
AB  - According to the Demographic and Health Surveys (DHS) in poorer countries, 50 %
      of women of reproductive age report that wife hitting or beating is justified.
      Such high rates may result from structural pressures to adopt such views or to
      report the perceived socially desirable response. In a survey experiment of 496
      ever-married women aged 18-49 years in rural Bangladesh, we compared responses to
      attitudinal questions that (1) replicated the 2007 Bangladesh DHS wording and
      portrayed the wife as transgressive for unstated reasons with elaborations
      depicting her as (2) unintentionally and (3) willfully transgressive. The
      probabilities of justifying wife hitting or beating were consistently low for
      unintended transgressions (.01-.08). Willful transgressions yielded higher
      probabilities (.40-.70), which resembled those based on the DHS wording (.38
      .57). Cognitive interviews illustrated that village women held diverse views,
      which were attributed to social change. Also, ambiguity in the DHS questions may
      have led some women to interpret them according to perceived gender norms and to
      give the socially desirable response of justified. Results inform modifications
      to these DHS questions and identify women for ideational-change interventions.

PMID- 22956418
TI  - Dialogical Self Theory and the increasing multiplicity of I-positions in a
      globalizing society: an introduction.
AB  - Dialogical Self Theory is a recent development in the social sciences, based on a
      conception of the self as a society of mind. In this conception, the self is
      considered as extended to significant others in the environment, who populate the
      self as a dynamic multiplicity of I-positions between which dialogical or
      monological relationships may emerge. While from a spatial perspective the self
      is engaged in a process of positioning and counterpositioning in a globalizing
      society, from a temporal point of view the self is part of a process of
      positioning and repositioning in collective history and personal development.
      Some phenomena that are necessary for the understanding of the dialogical self
      are discussed: dominance and social power, the processes of globalization and
      localization, the experience of uncertainty and possible reactions to uncertainty
      in a globalizing world. Finally, the different contributions of this special
      issue are placed in the context of the presented conceptual framework.

PMID- 22956417
TI  - Medicaid coverage for weight loss counseling may make 'cents'.

PMID- 22956419
TI  - Self and other dialogue in infancy: normal versus compromised developmental
      pathways.
AB  - Dialogical Self Theory, co-regulation, and foundational movement analysis are
      used to present a description of the development of the dialogical self during
      the first five months of life using observations of two mother-infant dyads.
      Susan and her mother illustrate normative emergence of the dialogical self.
      Susan's I-positions emerge through positive interactions with her mother, for
      example, through body positioning and dialogue in a flexible yield-push pattern.
      Peter, another infant we observed, and his mother show how the development of the
      dialogical self may be disrupted or delayed as rigid boundaries are formed
      between the mother and infant. Peter's tendency to withdraw, coupled with his
      mother's persistence at diminishing his positions, results in both avoidant and
      ambiguous monological positions in relation to his mother.

PMID- 22956420
TI  - Multicultural adolescents between tradition and postmodernity: Dialogical Self
      Theory and the paradox of localization and globalization.
AB  - This chapter builds on Dialogical Self Theory to investigate the identity
      development of adolescents growing up in multicultural societies. Their cultural
      identity is not only compounded by the rapid cultural changes associated with
      globalization, but also by the paradoxical revival of cultural traditions which
      the large-scale compression of time and space has incited at local levels of
      society. Dialogical Self Theory, which is based on the metaphor of the self as a
      "society of mind," helps to understand the dilemmas of tradition and
      postmodernity, of localization and globalization, within the self of individual
      youngsters.

PMID- 22956421
TI  - Mental sociality and collective identity: a dialogical analysis of the Indian
      sense of self.
AB  - This chapter discusses the specific strengths of Dialogical Self Theory for the
      exploration and explanation of the phenomenon of society of the mind as it is
      expressed in various intricate, culturally specific discourse strategies among
      Indians. By focusing on a recent social movement to demonstrate the particularity
      of cultural processes, personal and collective meanings are explored through
      interviews of several citizens during a protest. The examples explain how a
      dramatic event can cause people to react, review, and reconstruct their internal
      positions related to collective reality.

PMID- 22956422
TI  - Bridging theory: where cultures meet in self and science.
AB  - In this chapter, I argue that Dialogical Self Theory (DST) represents a
      compelling answer to how to conceptualize the psychology of the self in today's
      world, when people increasingly are aware of more than one way to think, feel,
      and relate to others. DST envisions a self of plural voices. The chapters in this
      volume show intriguing applications of the theory, ranging from microlevel infant
      caregiver interactions to macrolevel repercussions of globalization among Pacific
      island communities. I end by suggesting that the pliable nature of DST,
      illustrated in the chapter on an Indian social movement, is a strength. In my
      view, it fits with today's need for a new philosophy of social science. One-size
      fits-all approaches are often too broad and too biased to adequately capture the
      complexities of human selves and relations. The challenge and opportunity that we
      face today is one of bridging universal theories with cultural ones--and the
      present volume can be read as one example of how to meet that challenge with
      respect to a psychology of the self.

PMID- 22956423
TI  - beta2-glycoprotein I inhibits VEGF-induced endothelial cell growth and migration
      via suppressing phosphorylation of VEGFR2, ERK1/2, and Akt.
AB  - beta(2)-glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with diverse
      functions, but the impact and molecular effects of beta(2)-GPI on vascular
      biology are as yet unclear. Based on the limited information available on the
      contribution of beta(2)-GPI to endothelial cells, we investigated the effect of
      beta(2)-GPI on cell growth and migration in human aortic endothelial cells
      (HAECs). The regulation of beta(2)-GPI as part of intracellular signaling in
      HAECs was also examined. Vascular endothelial growth factor (VEGF) is a pro
      angiogenic factor that may regulate endothelial functions. We found that beta(2)
      GPI dose-dependently inhibited VEGF-induced endothelial cell growth using the 3
      (4,5-dimethylthiazol-2-yl)-2,5-dipenyl tetrazolium bromide assay and cell counts.
      Using wound healing and Boyden chamber assays, beta(2)-GPI remarkably reduced
      VEGF-increased cell migration at the physiological concentration. Furthermore,
      beta(2)-GPI suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2),
      extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt. These results
      suggest that beta(2)-GPI plays an essential role in the down-regulation of VEGF
      induced endothelial responses and may be a useful component for anti-angiogenic
      therapy.

PMID- 22956425
TI  - A higher-order analysis supports use of the 11-item version of the tampa scale
      for kinesiophobia in people with neck pain.
AB  - BACKGROUND: Despite increasing clinical and research use of the 11-item version
      of the Tampa Scale for Kinesiophobia (TSK-11) in people with neck pain, little is
      known about its measurement properties in this population. OBJECTIVE: The purpose
      of this study was to rigorously evaluate the measurement properties of the TSK-11
      when used in people with mechanical neck pain. DESIGN: This study was a secondary
      analysis of 2 independent databases (N=235) of people with mechanical neck pain
      of primarily traumatic origin. METHODS: The TSK-11 was subjected to Rasch
      analysis and subsequent evaluation of concurrent associations with the Neck
      Disability Index and a numeric rating scale for pain intensity. RESULTS: The TSK
      11 conformed well to the Rasch model for interval-level measurement, but less so
      for acute or nontraumatic etiologies. A transformation matrix suggested that
      small changes at the extremes of the scale are more meaningful than in the
      middle. Cross-sectional convergent validity testing suggested relationships of
      expected magnitude and direction compared with pain intensity and neck-related
      disability. The use of the linearly transformed TSK-11 led to potentially
      important differences in distribution of data compared with use of the raw
      scores. LIMITATIONS: The sample size was slightly smaller than desired for Rasch
      analysis. The 2 databases were similar in terms of symptom duration, but differed
      in pain intensity and age. CONCLUSIONS: The TSK-11 can be considered an interval
      level measure when used in people with neck pain. It provides potentially
      important information regarding the nature of neck-related disability. Clinically
      important difference may not be consistent across the range of the scale.

PMID- 22956424
TI  - MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or
      radioresistance in non-small cell lung cancer cells by targeting PTEN.
AB  - MicroRNAs (miRNAs) regulate gene expression by binding to target sites and
      initiating translational repression and/or mRNA degradation. In our previous
      study, we have shown that expression of serum microRNA (miR)-21 is correlated
      with TNM stage and lymph node metastasis and might be an independent prognostic
      factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC
      development are still unclear. The purpose of this study is to investigate the
      effect of miR-21 and determine whether miR-21 can be a therapeutic target for
      human NSCLC. Taqman real-time quantitative RT-PCR assay was performed to detect
      miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21
      expression on NSCLC cell characteristics including growth, invasion, and chemo-
      or radioresistance were also determined. Results showed that miR-21 is commonly
      upregulated in NSCLC cell lines and tissues with important functional
      consequences. In addition, we found that anti-miR-21 could significantly inhibit
      growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC
      cells, while miR-21 mimics could increase growth, promote migration and invasion,
      and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics
      could inhibit expression of PTEN mRNA and protein and the luciferase activity of
      a PTEN 3'-untranslated region (UTR)-based reporter construct in A549 cells, while
      anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase
      activity of a PTEN 3'-UTR-based reporter construct in A549 cells. Furthermore,
      overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC
      cells, and siRNA-mediated downregulation of PTEN could rescue the effects on
      NSCLC cells induced by anti-miR-21. Taken together, these results provide
      evidence to show the promotion role of miR-21 in NSCLC development through
      modulation of the PTEN signaling pathway.

PMID- 22956426
TI  - Level of agreement between methods for measuring moderate to vigorous physical
      activity and sedentary time in people with obstructive sleep apnea and obesity.
AB  - BACKGROUND: There is ambiguity about what measures to use to best identify
      physical activity and sedentary behavior, and agreement between methods for
      measuring physical activity and sedentary behavior in people with obstructive
      sleep apnea syndrome (OSAS) and obesity has not been evaluated. OBJECTIVE: The
      objective of this study was to examine the level of agreement between an
      accelerometer and a self-report questionnaire (International Physical Activity
      Questionnaire [IPAQ]) or a logbook for measuring time spent on moderate to
      vigorous physical activity and time spent sedentary in people with OSAS and
      obesity. DESIGN: This prospective study was a psychometric evaluation of
      agreement between measurement methods. METHODS: Thirty-nine people who were obese
      (body mass index: X=36.1 kg/m2, SD=4.35) and had moderate to severe OSAS (apnea
      hypopnea index of >=15) were consecutively recruited from a sleep clinic in
      Sweden. All were treated with continuous positive airway pressure and were
      waiting for a follow-up sleep evaluation. RESULTS: Agreement between the
      measurement methods was limited. For physical activity, the mean difference
      between the accelerometer and the IPAQ was 47 minutes, and the mean difference
      between the accelerometer and the logbook was 32 minutes. Agreement was limited
      for sedentary time as well; the mean difference between the accelerometer and the
      IPAQ was 114 minutes, and the mean difference between the accelerometer and the
      logbook was 86 minutes. LIMITATIONS: The small sample size may affect the
      interpretation and generalizability of the results. CONCLUSIONS: The results
      imply that the methods cannot be used interchangeably. A combination of an
      accelerometer and a daily logbook seems to provide a detailed description of
      physical activity and sedentary behavior.

PMID- 22956427
TI  - The clinical utility of the functional status score for the intensive care unit
      (FSS-ICU) at a long-term acute care hospital: a prospective cohort study.
AB  - BACKGROUND AND PURPOSE: Long-term acute care hospitals (LTACHs) have emerged for
      patients requiring medical care beyond a short stay. Minimal data have been
      reported on functional outcomes in this setting. The purposes of this study were:
      (1) to measure the clinical utility of the Functional Status Score for the
      Intensive Care Unit (FSS-ICU) in an LTACH setting and (2) to explore the
      association between FSS-ICU score and discharge setting. PARTICIPANTS: Data were
      obtained from 101 patients (median age=70 years, interquartile range [IQR]=61-78;
      39% female, 61% male) who were admitted to an LTACH. Participants were
      categorized into 1 of 5 groups by discharge setting: (1) home (n=14), (2)
      inpatient rehabilitation facility (n=26), (3) skilled nursing facility (n=23),
      (4) long-term care/hospice/expired (n=13), or (5) transferred to a short-stay
      hospital (n=25). METHODS: Data were prospectively collected from a 38-bed LTACH
      in the United States over 8 months beginning in September 2010. Functional status
      was scored using the FSS-ICU within 4 days of admission and every 2 weeks until
      discharge. The FSS-ICU consists of 5 categories: rolling, supine-to-sit
      transfers, unsupported sitting, sit-to-stand transfers, and ambulation. Each
      category was rated from 0 to 7, with a maximum cumulative FSS-ICU score of 35.
      RESULTS: Cumulative FSS-ICU scores significantly improved from a median (IQR) of
      9 (3-17) to 14 (5-24) at discharge. Median (IQR) cumulative discharge FSS-ICU
      scores were significantly different among the discharge categories: home=28 (22
      32), inpatient rehabilitation facility=21 (15-24), skilled nursing facility=14 (8
      21), long-term care/hospice/expired=5 (0-11), and transfer to a short-stay
      hospital=4 (0-7). DISCUSSION AND CONCLUSIONS: Patients receiving therapy at an
      LTACH demonstrate significant improvements from admission to discharge using the
      FSS-ICU. This outcome tool discriminates among discharge settings and
      successfully documents functional improvements of patients in an LTACH setting.

PMID- 22956428
TI  - The impact of body-scaled information on reaching.
AB  - BACKGROUND: Environmental and task modifications are powerful methods used to
      affect action in rehabilitation and are frequently used by therapists. OBJECTIVE:
      The purpose of this study was to examine and quantify the relationship between
      hand size (person characteristics) and object size (environmental
      characteristics) and the effect of this relationship on the emergent reaching
      patterns for children and adults with typical development. DESIGN: This was a
      cross-sectional prospective study. METHODS: Seventeen children and 20 adults
      participated and were required to reach and grasp 10 pairs of cubes of different
      sizes. The dimensionless ratios were calculated by dividing the cube size by the
      aperture between index finger and thumb to quantify emergent reach and grasp
      patterns. A critical ratio was used to establish the shift from a 1-handed to an
      exclusive 2-handed reach pattern. RESULTS: The results demonstrated no
      significant difference in the mean critical ratios between the 2 groups. However,
      a 2-handed reach was used more frequently than a 1-handed reach at a
      significantly smaller ratio for children in comparison with adults. LIMITATIONS:
      The relational metrics between the cube and hand are only one contribution to the
      emergent reaching and grasping patterns. CONCLUSIONS: Children had more
      variability of reaching patterns than adults. A personal constraint, such as
      experience, and a task constraint of accuracy may account for the variability.
      The results encourage further research on body-scaled information for individuals
      with different personal constraints (eg, children with cerebral palsy) and the
      impact of body-scaled information on emergent actions.

PMID- 22956429
TI  - Phase 1 trial of gemtuzumab ozogamicin in combination with enocitabine and
      daunorubicin for elderly patients with relapsed or refractory acute myeloid
      leukemia: Japan Adult Leukemia Study Group (JALSG)-GML208 study.
AB  - We conducted a phase 1 study of a combination of gemtuzumab ozogamicin (GO) plus
      conventional chemotherapy in elderly patients (>= 65 years old) with relapsed or
      refractory CD33-positive acute myeloid leukemia (AML). Patients received a
      standard dose of enocitabine (200 mg/m2 * 8 days) and daunorubicin (30 mg/m2 *
      days 1-3) plus an escalating dose of GO (1.5-5 mg/m2 on day 4). The dose
      escalation of GO was done according to a standard 3 + 3 design following a
      modified Fibonacci sequence. No dose-limiting toxicities were observed in three
      patients (median age, 71) at level 1 (1.5 mg/m2) or in three patients (median
      age, 73) at level 2 (3 mg/m2). Neither veno-occlusive diseases nor sinusoidal
      obstructive syndromes were noted at either level. However, as GO was withdrawn
      from the US market in June 2010, based on a randomized study in newly diagnosed
      AML, we decided not to proceed to the level 3 (5 mg/m2) in order to avoid
      possibly more severe adverse effects, and also because all six patients
      experienced grade 4 myelosuppression, with complete remission in three. This
      study showed that 3 mg/m2 of GO in combination with enocitabine and daunorubicin
      may be a recommendable dose for a phase 2 study in Japanese elderly patients with
      CD33-positive AML. The study was registered at the University Hospital Medical
      Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/
      ) as UMIN000002603.

PMID- 22956430
TI  - Net present biodiversity value and the design of biodiversity offsets.
AB  - There is an urgent need to develop sound theory and practice for biodiversity
      offsets to provide a better basis for offset multipliers, to improve accounting
      for time delays in offset repayments, and to develop a common framework for
      evaluating in-kind and out-of-kind offsets. Here, we apply concepts and measures
      from systematic conservation planning and financial accounting to provide a basis
      for determining equity across type (of biodiversity), space, and time. We
      introduce net present biodiversity value (NPBV) as a theoretical and practical
      measure for defining the offset required to achieve no-net-loss. For evaluating
      equity in type and space we use measures of biodiversity value from systematic
      conservation planning. Time discount rates are used to address risk of non
      repayment, and loss of utility. We illustrate these concepts and measures with
      two examples of biodiversity impact-offset transactions. Considerable further
      work is required to understand the characteristics of these approaches.

PMID- 22956431
TI  - Incidental occult gunshot wound detected by postmortem computed tomography.
AB  - The body of a 59 year old woman underwent postmortem computed tomography (PMCT)
      examination prior to forensic autopsy, using a 256 slice multidetector row
      computed tomography scanner. A large left tension pneumothorax detected on the
      PMCT was considered to be a likely cause of death and this was confirmed at
      autopsy. In addition there was an unsuspected PMCT finding of a probable gunshot
      injury traversing the right orbit, facial bones and frontal sinus. The autopsy
      technique was adjusted accordingly and PMCT findings confirmed. PMCT in this case
      was not only diagnostic of cause of death, but also revealed retained projectile
      fragments of an old gunshot wound to the face. Without prior imaging such
      findings would have been undetected at autopsy. This case further underscores the
      contribution of routine PMCT examination to forensic autopsy practice.

PMID- 22956432
TI  - A new model of acute care hospitals and the role of nephrologists.
AB  - Over the last decade, the Italian National Health Service has been widely
      criticized for failing to meet the expectations of the Italian population and to
      reduce the weaknesses of the health care system deriving from a lack of balance
      between increasing costs and comparable benefits. In order to improve health care
      services, a new model of acute care hospitals, characterized mainly by new
      structures, high technology, integration and collaboration among professionals,
      are necessary. The traditional concept of specialized operative unit is thus
      overcome by a new hospital organization in which specific functions are performed
      in shared facility areas. In particular, the role of the nephrologists will be
      reorganized into different health care settings according to the level of
      intensity of care: high level (intensive care unit, organ transplantation),
      intermediate level (medical area) or low intensity care facilities (day hospital,
      day surgery, day service, ambulatory).

PMID- 22956433
TI  - Vitamin E-coated polysulfone membrane improved red blood cell antioxidant status
      in hemodialysis patients.
AB  - BACKGROUND: Oxidative stress has emerged as a strong pathogenic cofactor
      implicated in the development of long-term complications in hemodialysis (HD)
      patients, such as anemia, and as a major component of the malnutrition
      inflammation complex syndrome. This prospective multicenter study aimed at
      evaluating the short-term effects of the new vitamin E (vitE)-coated polysulfone
      (PS) membrane (VitabranE) on biocompatibility performances and anemia in HD
      patients. METHODS: After a 3-month washout period with a high-flux synthetic
      dialyzer, 43 HD patients were switched to a vitE-PS dialyzer. Sampling was
      performed at baseline (corresponding to the end of the washout period) and after
      1, 2 and 3 months of treatment. Oxidative stress status, as well as inflammatory
      parameters, was investigated at the end of each study period. Hemoglobin levels
      and administered doses of recombinant human erythropoietin or epoetin (EPO) were
      available in each center. RESULTS: The use of vitE-coated membranes for 3 months
      was not associated with any change in inflammatory parameters. By contrast, vitE
      PS dialyzer resulted in a progressive increase in red blood cell (RBC) vitE
      concentration and in RBC superoxide dismutase activity. A concomitant progressive
      significant decrease in advanced oxidation protein product concentration at 2
      months was observed, suggesting a preventive effect on oxidative stress. Finally,
      a significant decrease of the erythropoietin resistance index was obtained after
      3 months of treatment. CONCLUSIONS: Use of the vitE-PS membrane during a short
      period improves erythrocyte antioxidant defense mechanisms and seems to lead to a
      reduction in EPO requirements in HD patients.

PMID- 22956434
TI  - Treatment of idiopathic membranous nephropathy with combination of low-dose
      tacrolimus and corticosteroids.
AB  - BACKGROUND: Evidence regarding the optimal dose of tacrolimus (TAC) in treatment
      of idiopathic membranous nephropathy (IMN) remains inconclusive. The objective of
      this study was to evaluate the efficacy and safety of low-dose TAC combined with
      prednisone for patients with IMN. METHODS: We conducted a randomized prospective
      cohort study in IMN patients: 28 patients received oral TAC (target whole blood
      concentration of 2-4 ng/mL) plus prednisone for 12 months, and 28 patients
      received prednisone combined with intravenous cyclophosphamide (CYC) (750 mg/m2
      body surface) once every 4 weeks for 24 weeks. RESULTS: Of the 56 patients who
      completed the 12-month treatment, complete remission (CR) occurred in 8 (28.6%)
      of the CYC group and 18 (64.3%) of the TAC group; partial remission (PR) occurred
      in 10 (35.7%) of the CYC group and 7 (25.0%) of the TAC group. The probability of
      remission (either CR or PR) was higher in the TAC group than in the CYC group (p
      = 0.0439, by log-rank test). Furthermore, a significantly greater improvement in
      proteinuria and serum albumin levels was observed in the TAC group compared with
      the CYC group. Patients treated with TAC can often show a rapid increase in their
      serum albumin levels before any obvious reduction of urinary protein excretion.
      Side effects were mild and transitory in both groups. CONCLUSION: The results
      demonstrated that the combined therapy of low-dose TAC and prednisone is an
      effective and safe therapeutic method for Chinese adults with IMN. Low-dose TAC
      accompanied by prednisone is enough to induce remission in the majority of
      patients with IMN.

PMID- 22956436
TI  - Refining hematopoietic cell transplant: a concise review.

PMID- 22956439
TI  - Isolation of a field strain of Brucella abortus from RB51-vaccinated- and
      brucellosis-seronegative bovine yearlings that calved normally.
AB  - A study was carried out in Pichucalco, Chiapas (Mexico) to determine whether
      recently calved cows or those that aborted shed Brucella. Serological diagnosis
      of brucellosis was made in all animals (209). Six of the cows that calved
      normally and two that aborted underwent a bacteriological study of milk and
      vaginal exudate. Brucella abortus was isolated from vaginal exudate samples in
      two 3- to 4-year-old seronegative first-birth cows that had calved normally. This
      was confirmed through bacteriological identification and PCR as a field strain
      and smooth phenotypes. We conclude that seronegative cows vaccinated with RB51
      which calved normally and shed B. abortus in the vaginal exudate after calving
      could be a serious problem because these cows are overlooked in routine diagnoses
      and are a source of Brucella infection.

PMID- 22956440
TI  - Effectiveness of vaccines and vaccination programs for the control of foot-and
      mouth disease in Uganda, 2001-2010.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals. In Uganda, FMD outbreaks are mainly controlled by ring vaccination and
      restriction of animal movements. Vaccination stimulates immunity and prevents
      animals from developing clinical signs which include lameness, inappetence, and
      decreased production. Ring vaccination and restriction of animal movements have,
      however, not successfully controlled FMD in Uganda and outbreaks reoccur
      annually. The objective of this study was to review the use of FMD virus (FMDV)
      vaccines and assess the effectiveness of vaccination programs for controlling FMD
      in Uganda (2001-2010), using retrospective data. FMD vaccine distribution
      patterns in Uganda (2001-2010) matched occurrence of outbreaks with districts
      reporting the highest number of outbreaks also receiving the largest quantity of
      vaccines. This was possibly due to "fire brigade" response of vaccinating animals
      after outbreaks have been reported. On average, only 10.3 % of cattle within
      districts that reported outbreaks during the study period were vaccinated. The
      average minimum time between onset of outbreaks and vaccination was 7.5 weeks,
      while the annual cost of FMDV vaccines used ranged from US $58,000 to 1,088,820.
      Between 2001 and 2010, serotyping of FMD virus was done in only 9/121 FMD
      outbreaks, and there is no evidence that vaccine matching or vaccine potency
      tests have been done in Uganda. The probability of FMDV vaccine and outbreak
      mismatch, the delayed response to outbreaks through vaccination, and the high
      costs associated with importation of FMDV vaccines could be reduced if virus
      serotyping and subtyping as well as vaccine matching were regularly done, and the
      results were considered for vaccine manufacture.

PMID- 22956441
TI  - Treatment targets in the management of dyslipidemias: which targets in whom?
AB  - The public health approach to prevention of atherosclerotic cardiovascular
      disease (ASCVD) continues to hold great potential for prevention. This approach
      includes diets low in saturated fats and cholesterol, maintaining desirable body
      weight, regular physical activity, and absence of cigarette smoking. But drug
      therapy is becoming more widely used. Statins have been available for treatment
      of elevated serum cholesterol for a quarter of a century. They have proven
      efficacious for reducing risk for atherosclerotic cardiovascular disease (ASCVD).
      They carry little toxicity, and now that some derivatives are generic, they are
      inexpensive. Statins have become standard of care for patients with established
      ASCVD. To achieve further reduction in ASCVD events through cholesterol lowering
      will require new combinations with older agents and development of new drugs. The
      future of secondary prevention lies in testing of old and new "add-on" agents.
      Indications for statin use in primary prevention is less clear-cut. But clinical
      trial experience with statins point to enormous potential for reducing ASCVD in
      the population. At the same time, there are dangers of overuse and turning
      society into a "drug culture". To abandon the benefits of healthy lifestyles for
      excessive drug intervention would be unfortunate.

PMID- 22956442
TI  - Butyrylcholinesterase as a prognostic marker: a review of the literature.
AB  - BACKGROUND: Butyrylcholinesterase (BChE) is an alpha-glycoprotein synthesized in
      the liver. Its serum level decreases in many clinical conditions such as acute
      and chronic liver damage, inflammation, injury and infections, and malnutrition.
      METHODS AND RESULTS: This review collects the main evidence on the emerging role
      of butyrylcholinesterase as a prognostic marker of liver and nonliver diseases as
      well as a marker of protein-energy malnutrition and obesity. In fact, serum
      concentrations and BChE activity seem to accurately reflect the availability of
      amino acidic substrates and/or derangement in protein synthesis due to
      hepatocellular damage. In cancer, with or without liver impairment, serum BChE
      levels serve as an accurate functional and prognostic indicator, useful for
      monitoring clinical and therapeutic interventions according to patients'
      prognosis. In the absence of inflammation, BChE could also serve as an index of
      the effectiveness of nutritional support. CONCLUSIONS: Serum BChE assessment
      should be included in routine clinical diagnostic procedures to evaluate patient
      clinical conditions, in particular in cases of inflammation and/or protein-energy
      malnutrition.

PMID- 22956443
TI  - Quality of life among obese patients seeking weight loss surgery: the importance
      of obesity-related social stigma and functional status.
AB  - BACKGROUND: Obesity is a stigmatizing condition associated with adverse
      psychosocial consequences. The relative importance of weight stigma in reducing
      health utility or the value a person places on their current health state is
      unknown. METHODS: We conducted a telephone survey of patients with obesity. All
      were seeking weight loss surgery at two bariatric centers (70 % response rate).
      We assessed patients' health utility (preference-based quality life measure) via
      a series of standard gamble scenarios assessing patients' willingness to risk
      death to lose various amounts of weight or achieve perfect health (range 0 to 1;
      0 = death and 1 = most valued health/weight state). Multivariable models assessed
      associations among quality of life domains from the Short-form 36 (SF-36) and
      Impact of Weight on Quality of Life-lite (IWQOL-lite) and patients' health
      utility. RESULTS: Our study sample (n = 574) had a mean body mass index of 46.5
      kg/m(2) and a mean health utility of 0.87, reflecting the group's average
      willingness to accept a 13 % risk of death to achieve their most desired
      health/weight state; utilities were highly variable, however, with 10 % reporting
      a utility of 1.00 and 27 % reporting a utility lower than 0.90. Among the IWQOL
      lite subscales, Public Distress and Work Life were the only two subscales
      significantly associated with patients' utility after adjustment for
      sociodemographic factors. Among the SF-36 subscales, Role Physical, Physical
      Functioning, and Role Emotional were significantly associated with patients'
      utility. When the leading subscales on both IWQOL-lite and SF-36 were considered
      together, Role Physical, Public Distress, and to a lesser degree Role Emotional
      remained independently associated with patients' health utility. CONCLUSION:
      Patients seeking weight loss surgery report health utilities similar to those
      reported for people living with diabetes or with laryngeal cancer; however,
      utility values varied widely with more than a quarter of patients willing to
      accept more than a 10 % risk of death to achieve their most valued health/weight
      state. Interference with role functioning due to physical limitations and obesity
      related social stigma were strong determinants of reduced health utility.

PMID- 22956444
TI  - A randomized, controlled trial of implementing the patient-centered medical home
      model in solo and small practices.
AB  - BACKGROUND: Transition to a Patient-Centered Medical Home (PCMH) is challenging
      in primary care, especially for smaller practices. OBJECTIVE: To test the
      effectiveness of providing external supports, including practice redesign, care
      management and revised payment, compared to no support in transition to PCMH
      among solo and small (<2-10 providers) primary care practices over 2 years.
      DESIGN: Randomized Controlled Trial. PARTICIPANTS: Eighteen supported practices
      (intervention) and 14 control practices (controls). INTERVENTIONS: Intervention
      practices received 6 months of intensive, and 12 months of less intensive,
      practice redesign support; 2 years of revised payment, including cost of National
      Council for Quality Assurance's (NCQA) Physician Practice Connections((r))
      Patient-Centered Medical HomeTM (PPC((r))-PCMHTM) submissions; and 18 months of
      care management support. Controls received yearly participation payments plus
      cost of PPC((r))-PCMHTM. MAIN MEASURES: PPC((r))-PCMHTM at baseline and 18
      months, plus intervention at 7 months. KEY RESULTS: At 18 months, 5 % of
      intervention practices and 79% of control practices were not recognized by NCQA;
      10% of intervention practices and 7% of controls achieved PPC((r))-PCMHTM Level
      1; 5% of intervention practices and 0% of controls achieved PPC((r))-PCMHTM Level
      2; and 80% of intervention practices and 14% of controls achieved PPC((r))-PCMHTM
      Level 3. Intervention practices were 27 times more likely to improve PPC((r))
      PCMHTM by one level, irrespective of practice size (p < 0.001) 95% CI (5-157).
      Among intervention practices, a multilevel ordinal piecewise model of change
      showed a significant and rapid 7-month effect (p(time7) = 0.01), which was twice
      as large as the sustained effect over subsequent 12 months (p(time18) = 0.02).
      Doubly multivariate analysis of variance showed significant differential change
      by condition across PPC((r))-PCMHTM standards over time (p(time x group)=0.03).
      Intervention practices improved eight of nine standards, controls improved three
      of nine (p(PPC1) = 0.009; p(PPC2) = 0.005; p(PPC3) = 0.007). CONCLUSIONS:
      Irrespective of size, practices can make rapid and sustained transition to a PCMH
      when provided external supports, including practice redesign, care management and
      payment reform. Without such supports, change is slow and limited in scope.

PMID- 22956445
TI  - Lichen sclerosus in a breast cancer survivor on an aromatase inhibitor: a case
      report.
AB  - Lichen sclerosus is a commonly misdiagnosed disease that is characterized by
      thinned, hypopigmented, crinkled skin that often forms a figure-eight shape
      around the vaginal and anal openings. We present a case of advanced lichen
      sclerosus in a 53-year-old female patient prescribed a nonsteroidal aromatase
      inhibitor after the excision of a breast cancer tumor. We present a diagnostic
      approach to lichen sclerosus by recognizing its common figure-eight pattern, and
      we review the known causes and treatment of lichen sclerosus. Research has shown
      that lichen sclerosus is more common in low estrogen states, and thus it is
      logical that aromatase inhibitors could increase a patient's risk for developing
      this disease. We therefore propose that all patients prescribed aromatase
      inhibitors undergo regular vulvo-vaginal exams to rule out lichen sclerosus and
      other hypoestrogen-related vulvo-vaginal problems.

PMID- 22956446
TI  - Confounding in the association of proton pump inhibitor use with risk of
      community-acquired pneumonia.
AB  - BACKGROUND: Use of proton pump inhibitors (PPIs) is associated with community
      acquired pneumonia (CAP), an association which may be confounded by unobserved
      patient and prescriber characteristics. OBJECTIVE: We assessed for confounding in
      the association between PPI use and CAP by using a 'falsification approach,'
      which estimated whether PPI use is also implausibly associated with other common
      medical conditions for which no known pathophysiologic link exists. DESIGN:
      Retrospective claims-based cohort study. SETTING: Six private U.S. health plans.
      SUBJECTS: Individuals who filled at least one prescription for a PPI (N = 26,436)
      and those who never did (N = 28,054) over 11 years. INTERVENTIONS: Multivariate
      linear regression of the association between a filled prescription for a PPI and
      a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested
      for implausible associations between PPI use in each quarter and rates of
      osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis
      (DVT), skin infection, and rheumatoid arthritis. Independent variables included
      an indicator for whether a prescription for a PPI was filled in a given quarter,
      and quarterly indicators for various co-morbidities, age, income, geographic
      location, and marital status. KEY RESULTS: Compared to nonusers, those ever using
      a PPI had higher adjusted rates of CAP in quarters in which no prescription was
      filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were
      noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151
      vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a
      prescription was filled were associated with higher adjusted rates of CAP (111
      vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain,
      597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to
      quarters in which no prescription was filled. CONCLUSION: PPI use is associated
      with CAP, but also implausibly associated with common medical conditions.
      Observed associations between PPI use and CAP may be confounded.

PMID- 22956447
TI  - ATP and ADP hydrolysis in cell membranes from rat myometrium.
AB  - Extracellular nucleotides affect female reproductive functions, fertilization,
      and pregnancy. The aim of this study was to investigate biochemical
      characteristics of ATP and ADP hydrolysis and identify E-NTPDases in myometrial
      cell membranes from Wistar albino rats. The apparent K (m) values were 506.4 +/-
      62.1 and 638.8 +/- 31.3 MUM, with a calculated V (max) (app) of 3,973.0 +/- 279.5
      and 2,853.9 +/- 79.8 nmol/min/mg for ATP and ADP, respectively. The enzyme
      activity described here has common properties characteristic for NTPDases:
      divalent cation dependence; alkaline pH optimum for both substrates,
      insensitivity to some of classical ATPase inhibitors (ouabain, oligomycine,
      theophylline, levamisole) and significant inhibition by suramine and high
      concentration of sodium azides (5 mM). According to similar apparent K(m) values
      for both substrates, the ATP/ADP hydrolysis ratio, and Chevillard competition
      plot, NTPDase1 is dominant ATP/ADP hydrolyzing enzyme in myometrial cell
      membranes. RT-PCR analysis revealed expression of three members of ectonucleoside
      triphosphate diphosphohydrolase family (NTPDase 1, 2, and 8) in rat uterus. These
      findings may further elucidate the role of NTPDases and ATP in reproductive
      physiology.

PMID- 22956449
TI  - Dose calculation with a cone beam CT image in image-guided radiation therapy.
AB  - A kilo-voltage cone-beam CT (CBCT) attached to a linear accelerator can verify a
      target position in each radiation therapy. If CBCT images can be used in dose
      calculation, we can verify an actual dose distribution on every treatment day.
      However, the CBCT images are degraded by several factors, and so we cannot use
      the CBCT images directly in place of conventional multi-slice CT (MSCT) images
      that are used in the initial dose planning. In this paper, we proposed a new
      method for using CBCT and MSCT images in the calculation of a dose distribution.
      Our proposed method segments the CBCT and MSCT images into regions of three major
      organs (lungs, bones and soft tissues) by use of histogram analysis. We also
      calculated a value such as the median of the MSCT numbers in each region of the
      MSCT images, and we set three representative values to the corresponding regions
      of the CBCT images. In the calculation of a dose distribution, we used these
      modified CBCT images. The validity of our method was confirmed with experiments
      in which we used images of a heterogeneous phantom and patients' lungs in
      comparison with conventional methods. The results showed that the dose
      distribution determined by our method was similar to that of the initial dose
      plan, and our method was superior to the conventional methods in terms of pass
      rates of a distance-to-agreement analysis and gamma analysis. The results of a
      dose-volume-histogram analysis also showed the accuracy of our proposed method.

PMID- 22956448
TI  - SJSZ glycoprotein (38 kDa) modulates macrophage type 1/2-related factors at
      hepatocarcinogenic stage in N-nitrosodiethylamine-treated Balb/c.
AB  - Macrophage plays critical role for tumor progression: Type 1 (M1) for tumor
      prevention and type 2 (M2) for promotion in hepatocellular carcinoma. In order to
      study the chemopreventive effects of the SJSZ glycoprotein (38 kDa) on M1- or M2
      related factors, Balb/c was injected intraperitoneally with N-nitrosodiethylamine
      (DEN; 50 mg/kg, BW) for 7 weeks. After 7 weeks, the mice were sacrificed. After
      that, peritoneal macrophages were isolated. We evaluated the production of
      reactive oxygen species (ROS) and nitric oxide (NO), hepatocarcinogenic signals
      [activities of mitogen-activated associated kinase (MAPKs), inducible nitric
      oxide synthase (iNOS), nuclear factor (NF)-kappaB, and signal transducer and
      activator of transcription (STAT) 6,], cytokines [interleukin (IL)-10, IL-4, IL
      12, and interferon (IFN)-gamma], and CD163-positive macrophages (M2 polarization)
      using biochemical methods, immunoblot analysis, qRT-PCR, ELISA, and flow
      cytometry. The results revealed that the SJSZ glycoprotein (10 mg/kg, BW)
      inhibits the phosphorylation of MAPKs and expression of NF-kappaB, pSTAT6, IL-10,
      and IL-4; and normalizes production of ROS and NO, and expression of iNOS, IL-12,
      and IFN-gamma. Especially, it inhibited CD163-positive macrophages. In
      conclusion, these results indicated that SJSZ glycoprotein modulates polarization
      of macrophage type 1 and type 2 at hepatocarcinogenic initial stage in DEN
      treated Balb/c. Thus, SJSZ glycoprotein may be useful as one of immunomodulating
      agents which have to regulate M1- and M2-related factors to prevent tumor
      progression.

PMID- 22956450
TI  - Unusual suicide using a table saw.

PMID- 22956451
TI  - Running like Alice and losing good ideas: on the quasi-compulsive use of English
      by non-native English speaking scientists.

PMID- 22956452
TI  - Survey of overnight academic hospitalist supervision of trainees.
AB  - In 2003, Accreditation Council for Graduate Medical Education (ACGME) announced
      the first in a series of guidelines related to the residency training. The most
      recent recommendations include explicit recommendations regarding the provision
      of on-site clinical supervision for trainees of internal medicine. To meet these
      standards, many internal medicine residency programs turned to hospitalist
      programs to fill that need. However, much is unknown about the current
      relationships between hospitalist and residency programs, specifically with
      regard to supervisory roles and supervision policies. We aimed to describe how
      academic hospitalists currently supervise housestaff during the on-call, or
      overnight, period and hospitalist program leader their perceptions of how these
      new policies would impact trainee-hospitalist interactions.

PMID- 22956453
TI  - Solid-phase chemical synthesis of 5'-triphosphate DNA, RNA, and chemically
      modified oligonucleotides.
AB  - A chemical method for the solid-phase synthesis of 5'-triphosphate
      oligonucleotides is described. The full-length oligonucleotides are first
      constructed using standard solid-phase DNA/RNA synthesis, and then efficient
      implementation of a sequential 4-steps synthetic procedure, executed either
      manually or in a fully automated fashion, affords the corresponding solid
      supported 5'-triphosphate oligonucleotides. Using this synthetic procedure, the
      full-length 5'-hydroxyl oligonucleotides are initially transformed into the
      corresponding 5'-H-phosphonate mono esters, subsequently oxidized in the presence
      of imidazole to the activated 5'-phosphorimidazolidates, and finally reacted with
      pyrophosphate on the solid support. The method uses safe, stable, and inexpensive
      reagents, and the process is scalable and readily applicable to automated
      synthesis compatible with the current commercially available DNA/RNA
      synthesizers. After cleavage from the solid support and deprotection, a range of
      DNA, RNA, and chemically modified 5'-triphosphate oligonucleotides are obtained
      in a convenient and efficient manner and isolated in good yields after HPLC
      purification.

PMID- 22956455
TI  - Crystallography of DNA and RNA G-quadruplex nucleic acids and their ligand
      complexes.
AB  - Quadruplexes are higher-order structures formed by natural guanine-rich nucleic
      acid sequences. They may play a role in gene regulation and in telomere function.
      This article focuses on the crystallization of quadruplexes and their complexes
      with small-molecule ligands. Protocols for successful crystallization, as used in
      the author's laboratory, are described in detail.

PMID- 22956454
TI  - Sequence, stability, and structure of G-quadruplexes and their interactions with
      drugs.
AB  - Although DNA is most widely known for its ability to store and pass along genetic
      information, the discovery of G-quadruplex structures has illuminated a new role
      for DNA in biology. DNA G-quadruplexes are four-stranded globular nucleic acid
      secondary structures formed in specific G-rich sequences with biological
      significance, such as human telomeres and oncogene promoters. This review focuses
      on the unimolecular DNA G-quadruplexes, which can readily form in solution under
      physiological conditions and are considered to be the most biologically relevant.
      Available structural data show a great conformational diversity of unimolecular G
      quadruplexes, which are amenable to small-molecule drug targeting. The
      relationships between sequence, structure, and stability of unimolecular DNA G
      quadruplexes, as well as the recent progress on interactions with small-molecule
      compounds and insights into rational design of G-quadruplex-interactive
      molecules, will be discussed.

PMID- 22956456
TI  - Preparation of azido containing oligonucleotides through diazo transfer reaction.
AB  - The use of diazo transfer reagent, imidazole-1-sulfonyl azide hydrochloride
      (ISAHC), in the presence of Cu(2+) cation enables clean and efficient conversion
      of aminated oligodeoxyribonucleotides (ODNs) into their azido counterparts under
      mild conditions. ODNs bearing amino tether either at the 3', 5', or any internal
      position could be modified in this way, thus demonstrating the versatility of
      this reaction. The method also benefits from the commercial availability or easy
      access by routine automated DNA synthesis of amino-containing
      oligodeoxyribonucleotide starting material. Easy access to such azido-modified
      ODNs is of great interest for conjugation in particular through copper catalyzed
      1,3-dipolar cycloaddition (CuAAC reaction).

PMID- 22956457
TI  - Synthesis of threose nucleic acid (TNA) phosphoramidite monomers and
      oligonucleotide polymers.
AB  - This unit describes the preparation of dimethoxytrityl (DMTr)-protected alpha-L
      threofuranosyl nucleic acid (TNA) phosphoramidite monomers for A, C, G, T, and
      diaminopurine, as well as their incorporation into TNA oligonucleotides by solid
      phase synthesis. Starting from commercially available L-ascorbic acid, the
      protected threofuranosyl sugar is obtained in four steps. Vorbruggen-Hilbert
      Johnson glycosylation affords the desired threofuranosyl nucleosides, which are
      converted to their corresponding DMTr-protected phosphoramidite nucleosides in
      four additional steps. Phosphoramidite monomers are then used to construct TNA
      oligonucleotides by solid-phase synthesis using a standard DNA synthesizer.

PMID- 22956458
TI  - Convenient and efficient approach to the permanent or reversible conjugation of
      RNA and DNA sequences with functional groups.
AB  - The conversion of 3',5'-disilylated 2'-O-(methylthiomethyl)ribonucleosides to 2'
      O-(phthalimidooxymethyl)ribonucleosides is achieved in yields of 66% to 94%.
      Desilylation and dephtalimidation of these ribonucleosides by treatment with
      NH(4)F in MeOH produce 2'-O-aminooxymethylated ribonucleosides, which are
      efficient in producing stable and yet reversible 2'-conjugates upon reaction with
      1-pyrenecarboxaldehyde. Exposure of 2'-pyrenylated ribonucleosides to 0.5 M tetra
      n-butylammonium fluoride (TBAF) in THF or DMSO results in the cleavage of their
      iminoether functions to give the native ribonucleosides along with an innocuous
      nitrile side product. Conversely, the reaction of 2'-O-(aminooxymethyl)uridine
      with 5-cholesten-3-one leads to a permanent uridine 2'-conjugate, which is left
      unreacted when treated with TBAF. The versatility and uniqueness of 2'-O
      (aminooxymethyl)ribonucleosides is demonstrated by the single or double
      incorporation of a reversible pyrenylated uridine 2'-conjugate into an RNA
      sequence. Furthermore, the conjugation of 2'-O-(aminooxymethyl)ribonucleosides
      with various aldehydes, including those generated from their acetals, is also
      presented. The preparation of 5'-O-(aminooxymethyl)thymidine is also achieved,
      albeit in modest yields, from the conversion of 5'-O-methylthiomethyl-3'-O
      (levulinyl)thymidine to 5'-O-phthalimidooxymethyl-3'-O-(levuliny)lthymidine
      followed by hydrazinolysis of both 5'-phthalimido and 3'-levulinyl groups.
      Pyrenylation of the 5'-O-(aminooxymethyl)deoxyribonucleoside also provides a
      reversible 5'-conjugate that is sensitive to TBAF, thereby further demonstrating
      the usefulness of 5'-O-(aminooxymethyl)deoxyribonucleosides for permanent or
      reversible modification of DNA sequences. Curr. Protoc. Nucleic Acid Chem.
      50:4.52.1-4.52.36. (c) 2012 by John Wiley & Sons, Inc.

PMID- 22956461
TI  - Effects of cyclosporine on bone mineral density in patients with glucocorticoid
      dependent nephrotic syndrome in remission.
AB  - PURPOSE: Cyclosporine (CsA) is often prescribed to patients with glucocorticoid
      (GC)-dependent nephrotic syndrome. Although it is well known that long-term
      administration of GC causes osteoporosis, the effects of CsA on bone metabolism
      are not fully established. Therefore, we examined the effects of CsA on bone
      metabolism in patients with GC-dependent nephrotic syndrome in remission.
      METHODS: We followed 23 patients treated with prednisolone alone (GC alone group)
      and 17 patients treated with CsA in combination with prednisolone (GC + CsA
      group). Bone mineral density (BMD) was measured by dual-energy X-ray
      absorptiometry, and biochemical markers of bone metabolism were simultaneously
      measured in serum and urine samples. RESULTS: BMD decreased significantly in the
      GC group from 752 to 623 mg/cm(2) but non-significantly in the GC + CsA group
      from 751 to 684 mg/cm(2). Although the cumulative dose of GC increased in both
      groups, there were no significant differences in biochemical markers at either
      the start or the end of the study. Vertebrate bone fracture and other side
      effects associated with CsA treatment did not occur in our study. CONCLUSIONS:
      Our results indicate that CsA does not accelerate GC-induced osteoporosis in
      patients with nephrotic syndrome. We conclude that CsA is appropriate for the
      treatment of GC-dependent nephrotic syndrome, because it does not adversely
      affect bone metabolism and has favorable glomerular effects.

PMID- 22956459
TI  - Diabetes resilience: a model of risk and protection in type 1 diabetes.
AB  - Declining diabetes management and control are common as children progress through
      adolescence, yet many youths with diabetes do remarkably well. Risk factors for
      poor diabetes outcomes are well-researched, but fewer data describe processes
      that lead to positive outcomes such as engaging in effective diabetes self
      management, experiencing high quality of life, and achieving in-range glycemic
      control. Resilience theory posits that protective processes buffer the impact of
      risk factors on an individual's development and functioning. We review recent
      conceptualizations of resilience theory in the context of type 1 diabetes
      management and control and present a theoretical model of pediatric diabetes
      resilience. Applications to clinical care and research include the development of
      preventive interventions to build or strengthen protective skills and processes
      related to diabetes and its management. The ultimate goal is to equip youths with
      diabetes and their families with the tools to promote both behavioral and health
      related resilience in diabetes.

PMID- 22956462
TI  - Nutcracker phenomenon in combination with glomerular nephritis in isolated
      hematuria patients.
AB  - OBJECTIVES: This study aims to analyze the relationship between nutcracker
      syndrome (NCS) and nutcracker phenomenon (NCP) in glomerular nephritis (GN) of
      patients with symptom of isolated hematuria. Our observations reveal that
      patients with combined GN and NCP/NCS have dysmorphic urine red blood cells or
      mixed-morphological urine red blood cells while patients with NCS only (without
      GN) contain isomorphic urine red blood cells. PATIENTS AND METHODS: Clinical and
      pathological data of 32 patients with NCP and complicating GN were analyzed. A
      different group of 17 patients with NCS served as the control. All patients
      underwent color Doppler ultrasonography. Routine urine examination, red blood
      cell counts, and phase observations of urinary sediments were performed both
      before and after exercise. twenty four hour urinary protein and albumin
      quantities were determined. Twenty-nine patients underwent renal needle biopsy.
      RESULTS: All 32 patients were diagnosed with NCP. Results of urinary sediment
      examination of patients were either normal or showed isomorphic hematuria before
      exercise. Most patients exhibited mixed-morphological or dysmorphic hematuria at
      different degrees after exercise. Renal pathological findings in 29 patients
      included multiple types and showed no relevance to urinary examination results.
      All patients diagnosed with GN complicated by NCP were identified through
      clinical and laboratory examinations and renal biopsy. CONCLUSIONS: NCP may
      coexist with a glomerular disease. NCS patients with urine red blood cells of
      mixed morphology or showing dysmorphism after exercise should be noted, with or
      without the coexistence of GN. Renal needle biopsy must be performed when
      necessary to avoid adverse effects on the patient's condition.

PMID- 22956460
TI  - Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney
      disease among Nigerians.
AB  - PURPOSE: A region of chromosome 22 which includes APOL1 and MYH9 genes was
      recently identified as a risk locus for non-diabetic forms of kidney disease,
      including idiopathic and HIV-associated focal segmental glomerular sclerosis and
      kidney disease clinically attributed to hypertension among African Americans. The
      purposes of the current study were, therefore, to examine the frequency of these
      variants and to determine whether they are associated with chronic kidney disease
      (CKD) among native Africans. METHODS: To investigate the possible evidence of
      association between variants in these genes and non-diabetic CKD among West
      Africans, we performed a case/control analysis in a sample of 166 Nigerians
      without history of European admixture. Our study included a total of 9 variants
      on APOL1 (n = 4) and MYH9 (n = 5) genes. RESULTS: We observed significantly
      strong associations with previously reported APOL1 variants rs73885319 and
      rs60910145, and their two-allele "G1" haplotype (P < 0.005). We did not observe
      significant evidence of association between non-diabetic CKD and any of the MYH9
      variants or haplotypes after accounting for multiple testing in our sample.
      CONCLUSIONS: In conclusion, APOL1 risk variants are associated with non-diabetic
      forms of CKD among Nigerians of Yoruba ethnicity. Further information on
      APOL1/MYH9 variants may lead to screening programs, which could lead to earlier
      detection and interventions for non-diabetic kidney disease.

PMID- 22956463
TI  - Effects of ginkgoneolic acid on the growth, acidogenicity, adherence, and biofilm
      of Streptococcus mutans in vitro.
AB  - Ginkgo biloba has long been used in traditional Chinese medicine. In this study,
      ginkgoneolic acid, a kind of compound extracted from G. biloba, was investigated
      for its effects on growth, acid production, adherence, biofilm formation, and
      biofilm morphology of Streptococcus mutans. The results showed that ginkgoneolic
      acid inhibited not only the growth of S. mutans planktonic cells at minimum
      inhibitory concentration (MIC) of 4 MUg/mL and minimum bactericidal concentration
      (MBC) of 8 MUg/mL but also the acid production and adherence to saliva-coated
      hydroxyapatite of S. mutans at sub-MIC concentration. In addition, this agent was
      effective in inhibiting the biofilm formation of S. mutans (MBIC(50) = 4 MUg/mL),
      and it reduced 1-day-developed biofilm of S. mutans by 50 % or more at low
      concentration (MBRC(50) = 32 MUg/mL). Furthermore, the present study demonstrated
      that ginkgoneolic acid disrupted biofilm integrity effectively. These findings
      suggest that ginkgoneolic acid is a natural anticariogenic agent in that it
      exhibits antimicrobial activity against S. mutans and suppresses the specific
      virulence factors associated with its cariogenicity.

PMID- 22956464
TI  - Detection of primary clarithromycin resistance of Helicobacter pylori and
      association between cagA (+) status and clinical outcome.
AB  - Helicobacter pylori was examined in 110 patients (82 (74.5) with gastritis, 18
      (16.4) with duodenitis, six (5.5) with duodenal ulcer and gastroesophageal
      reflux, and four (3.6 %) with normal) with gastrointestinal problems living in
      rural area, no history of macrolide use, and detected by culture (71.8) or direct
      detection from gastric biopsies by PCR (82.7 %). Also, cagA gene was identified
      using PCR and was found positive in 68/91 (74.7 %) strains. The prevalence of
      clarithromycin-resistant H. pylori was investigated by two methods including PCR
      RFLP (7.7 (A2142G 1.1 and A2143G 6.6 %)) and twofold agar dilution (8.9 %) to
      detect phenotypic and genotypic status simultaneously. Among all the H. pylori
      positive patients, eight (8.8 %) isolates were found to be resistant to
      clarithromycin by at least one of the AD and/or PCR-RFLP methods. H. pylori
      positive rates were significantly correlated with patients' sex, age, and
      endoscopic findings (p = 0.040, <0.001 and <0.001, respectively). There were no
      differences in gender or endoscopic findings related to cagA (+) and cagA (-)
      patients. The gene of cagA was not significantly helpful in predicting the
      clinical outcome of H. pylori infection alone. In conclusion, we revealed that
      there was a low prevalence of primer clarithromycin resistance in patients living
      in rural area with no history of macrolide use. The prevalence of mutant strains
      among the macrolide-resistant H. pylori varies even geographically between close
      provinces.

PMID- 22956465
TI  - Protein adsorption on nano-scaled, rippled TiO2 and Si surfaces.
AB  - We synthesized nano-scaled periodic ripple patterns on silicon and titanium
      dioxide (TiO(2)) surfaces by xenon ion irradiation, and performed adsorption
      experiments with human plasma fibrinogen (HPF) on such surfaces as a function of
      the ripple wavelength. Atomic force microscopy showed the adsorption of HPF in
      mostly globular conformation on crystalline and amorphous flat Si surfaces as
      well as on nano-structured Si with long ripple wavelengths. For short ripple
      wavelengths the proteins seem to adsorb in a stretched formation and align across
      or along the ripples. In contrast to that, the proteins adsorb in a globular
      assembly on flat and long-wavelength rippled TiO(2), but no adsorbed proteins
      could be observed on TiO(2) with short ripple wavelengths due to a decrease of
      the adsorption energy caused by surface curvature. Consequently, the adsorption
      behavior of HPF can be tuned on biomedically interesting materials by introducing
      a nano-sized morphology while not modifying the stoichiometry/chemistry.

PMID- 22956466
TI  - Three-dimensional carbon nanotube electrodes for extracellular recording of
      cardiac myocytes.
AB  - Low impedance at the interface between tissue and conducting electrodes is of
      utmost importance for the electrical recording or stimulation of heart and brain
      tissue. A common way to improve the cell-metal interface and thus the signal-to
      noise ratio of recordings, as well as the charge transfer for stimulation
      applications, is to increase the electrochemically active electrode surface area.
      In this paper, we propose a method to decrease the impedance of microelectrodes
      by the introduction of carbon nanotubes (CNTs), offering an extremely rough
      surface. In a multistage process, an array of multiple microelectrodes covered
      with high quality, tightly bound CNTs was realized. It is shown by impedance
      spectroscopy and cardiac myocyte recordings that the transducer properties of the
      carbon nanotube electrodes are superior to conventional gold and titanium nitride
      electrodes. These findings will be favorable for any kind of implantable heart
      electrodes and electrophysiology in cardiac myocyte cultures.

PMID- 22956467
TI  - SLAP deficiency increases TCR avidity leading to altered repertoire and negative
      selection of cognate antigen-specific CD8+ T cells.
AB  - How T cell receptor (TCR) avidity influences CD8(+) T cell development and
      repertoire selection is not yet fully understood. To fill this gap, we utilized
      Src-like adaptor protein (SLAP)-deficient mice as a tool to increase TCR avidity
      on double positive (DP) thymocytes. We generated SLAP(-/-) mice with the
      transgenic MHC class I-restricted TCR (OT-1) and SLAP(-/-) Vbeta5 mice,
      expressing only the beta-chain of the TCR OT-1 transgene, to examine the effects
      of increased TCR surface levels on CD8(+) T cell development and repertoire
      selection. In comparing SLAP(-/-) OT-1 and Vbeta5 mice with wild-type controls,
      we performed compositional analysis and assessed thymocyte signaling by measuring
      CD5 levels. In addition, we performed tetramer and compositional staining to
      measure affinity for the cognate antigen, ovalbumin (OVA) peptide, presented by
      MHC. Furthermore, we quantified differences in alpha-chain repertoire in SLAP(-/
      ) Vbeta5 mice. We have found that SLAP(-/-) OT-1 mice have fewer CD8(+)
      thymocytes but have increased CD5 expression. SLAP(-/-) OT-1 mice have fewer DP
      thymocytes expressing Valpha2, signifying increased endogenous alpha-chain
      rearrangement, and more non-OVA-specific CD8(+) splenocytes upon tetramer
      staining. Our data demonstrate that SLAP(-/-) Vbeta5 mice also have fewer OVA
      specific cells and increased Valpha2 usage in the peripheral Vbeta5 CD8(+) T
      cells that were non-OVA-specific, demonstrating differences in alpha-chain
      repertoire. These studies provide direct evidence that increased TCR avidity in
      DP thymocytes enhances CD8(+) T cell negative selection deleting thymocytes with
      specificity for cognate antigen, an antigen the mature T cells may never
      encounter. Collectively, these studies provide new insights into how TCR avidity
      during CD8(+) T cell development influences repertoire selection.

PMID- 22956468
TI  - Peripheral tolerance and autoimmunity: lessons from in vivo imaging.
AB  - Multi-photon microscopy has taken hold as a widely used technique in immunology,
      allowing for imaging of the kinetics of immune cell motility and cell-cell
      interactions, but what have we learned from this technique about the processes
      involved in peripheral tolerance and autoimmunity? Various studies have now
      looked at the dynamics of several mechanisms of peripheral T cell tolerance and
      efforts to examine the dynamics of the autoimmune response at the disease site
      are also under way. Here, we will discuss the findings of studies that use multi
      photon microscopy to examine the dynamics of T cell tolerance in the lymph nodes
      and of the autoimmune processes involved in models of type 1 diabetes and
      multiple sclerosis. An emerging theme from these studies is that short T cell
      antigen presenting cell interactions can lead to tolerance, and that autoreactive
      T cell restimulation at the disease site can play an important role in autoimmune
      disease exacerbation.

PMID- 22956469
TI  - Type 1 diabetes: primary antigen/peptide/register/trimolecular complex.
AB  - Type 1A diabetes (autoimmune) is now immunologically predictable in man, but
      preventable only in animal models. What triggers the development of autoimmunity
      in genetically susceptible individuals remains unknown. Studies of non-obese
      diabetic (NOD) mice reveal that interactions between T-cell receptors of
      diabetogenic T cell and an MHC class II loaded with an autoantigen are key
      determinates of the disease. With insulin as the primary target in the NOD mouse,
      likely man, and possibly the RT1-U rat models, therapeutic targeting of the
      components of these anti-insulin trimolecular complexes we believe provide a
      fulcrum for development of preventive therapy. In particular for the NOD mouse
      model, there is extensive evidence that the dominant insulin peptide driving
      disease initiation is insulin B chain amino acids 9-23 (SHLVEALYLVCGERG)
      recognized predominantly by germ-line sequences of a specific T-cell receptor
      Valpha (TRAV5D-4), and small molecules or monoclonal antibodies directed at this
      recognition complex can prevent diabetes.

PMID- 22956470
TI  - Ribosomal DNA distribution and a genus-wide phylogeny reveal patterns of
      chromosomal evolution in Alstroemeria (Alstroemeriaceae).
AB  - PREMISE OF THE STUDY: Understanding the flexibility of monocot genomes requires a
      phylogenetic framework, which so far is available for few of the ca. 2800 genera.
      Here we use a molecular tree for the South American genus Alstroemeria to place
      karyological information, including fluorescent in situ hybridization (FISH)
      signals, in an explicit evolutionary context. METHODS: From a phylogeny based on
      plastid, nuclear, and mitochondrial sequences for most species of Alstroemeria,
      we selected early-branching (Chilean) and derived (Brazilian) species for which
      we obtained 18S-25S and 5S rDNA FISH signals; we also analyzed chromosome
      numbers, 1C-values, and telomere FISH signals (in two species). KEY RESULTS:
      Chromosome counts for Alstroemeria cf. rupestris and A. pulchella confirm 2n = 16
      as typical of the genus, which now has chromosomes counted for 29 of its 78
      species. The rDNA sites are polymorphic both among and within species, and
      interstitial telomeric sites in Alstroemeria cf. rupestris suggest chromosome
      fusion. CONCLUSIONS: In spite of a constant chromosome number, closely related
      species of Alstroemeria differ drastically in their rDNA, indicating rapid
      increase, decrease, or translocations of these genes. Previously proposed
      Brazilian and Chilean karyotype groups are not natural, and the n = 8 chromosomes
      in Alstroemeria compared to n = 9 in its sister genus Bomarea may result from a
      Robertsonian fusion.

PMID- 22956471
TI  - Clinical presentation and outcome of perioperative myocardial infarction in the
      very elderly following hip fracture surgery.
AB  - BACKGROUND: Patterns of clinical symptoms and outcomes of perioperative
      myocardial infarction (PMI) in elderly patients after hip fracture repair surgery
      are not well defined. METHODS: A retrospective 1:2 case-control study in a cohort
      of 1212 elderly patients undergoing hip fracture surgery from 1988 to 2002 in
      Olmsted County, Minnesota. RESULTS: The mean age was 85.3 +/- 7.4 years; 76%
      female. PMI occurred in 167 (13.8%) patients within 7 days, of which 153 (92%)
      occurred in first 48 hours; 75% of patients were asymptomatic. Among patients
      with PMI, in-hospital mortality was 14.4%, 30-day mortality was 29 (17.4%), and 1
      year mortality was 66 (39.5%). PMI was associated with a higher inpatient
      mortality rate (odds ratio [OR], 15.1; confidence interval [CI], 4.6-48.8), 30
      day mortality (hazard ratio [HR], 4.3; CI, 2.1-8.9), and 1-year mortality (HR,
      1.9; CI, 1.4-2.7). CONCLUSION: Elderly patients, after hip fracture surgery, have
      a higher incidence of PMI and mortality than what guidelines indicate. The
      majority of elderly patients with PMI did not experience ischemic symptoms and
      required cardiac biomarkers for diagnosis. The results of our study support the
      measurement of troponin in postoperative elderly patients for the diagnosis of
      PMI, in order to implement in-hospital preventive strategies to reduce PMI
      associated mortality.

PMID- 22956472
TI  - Clinical and histologic predictors of voice and disease outcome in patients with
      early glottic cancer.
AB  - OBJECTIVES/HYPOTHESIS: To determine preliminarily if clinical or histological
      features of patients with laryngeal dysplasia/early carcinoma correlate with
      voice and disease outcomes. STUDY DESIGN: Retrospective case series. METHODS: All
      UCSF Voice Center patients treated with endoscopic surgery for severe dysplasia
      or early laryngeal cancer between 2004 and 2010 were identified. Preoperative
      stroboscopy, intraoperative appearance, and histologic characteristics (pattern
      of invasion, degree of inflammation, and degree of keratinization) of the
      neoplastic lesions were compared with cordectomy type and the outcomes of voice
      quality and disease-free interval. RESULTS: Eighteen patients were evaluated.
      Increased stromal chronic inflammation correlated with longer disease-free
      interval (r(2) = 0.38). Cordectomy type correlated with both preoperative and
      postoperative voice parameters (r(2) = 0.42-0.68 and 0.33-0.39). CONCLUSION:
      Increased stromal chronic inflammation correlates with improved disease outcome.
      Voice outcome correlates with the amount of tissue removed. The clinical
      appearance of the lesion did not correlate with disease or voice outcome.

PMID- 22956473
TI  - Efficacy and safety of voriconazole in the treatment of chronic pulmonary
      aspergillosis: experience in Japan.
AB  - BACKGROUND: Though various clinical conditions of aspergillosis can occur,
      depending essentially on the host's immunological status, the focus of research
      in North American and European countries has mainly been on invasive pulmonary
      aspergillosis in immunocompromised patients. There are, however, also many
      problems to overcome in chronic forms of aspergillosis. One of those problems is
      that there are no codified treatment guidelines for chronic pulmonary
      aspergillosis (CPA). Especially in Japan, this issue is more serious, because
      there are more cases with CPA due to the many aged people with past history of
      tuberculosis. Several clinical cases and case series have reported the usefulness
      of the various antifungal agents that are available. The new triazole,
      voriconazole, in particular, seems to be effective in the treatment of CPA. The
      aim of the present study is to evaluate the efficacy and safety of voriconazole
      in the treatment of CPA in non-immunocompromised patients. PATIENTS AND METHODS:
      We conducted a prospective, open-label, non-comparative, multicenter study over a
      2-year period. For inclusion in the study, patients with confirmed or probable
      CPA were recruited in 11 hospitals of the National Hospital Organization in
      Japan. Clinical, radiological, serological, and mycological data were collected
      at baseline and 12 weeks after treatment or at the end of treatment. RESULTS:
      Among 77 patients enrolled in the study, 71 patients (mean age 65.9 years, 56
      males and 15 females) were eligible for the study. All of the eligible patients
      presented with underlying lung diseases, including sequelae of tuberculosis (n =
      35), non-tuberculous mycobacterial lung disease (n = 8), chronic obstructive
      pulmonary disease (COPD) (n = 8), interstitial pneumonia (n = 7), cystic lung
      disease (n = 4), pneumothorax (n = 3), bronchial cancer (n = 1), and others (n =
      5). Voriconazole was indicated in 48 cases (68 %) as the first-line treatment for
      CPA and 23 patients previously received other antifungal therapies. Based on a
      composite of clinical, radiologic, serological, and mycologic criteria, good
      response was seen in 43 patients (60.6 %), no response was observed in 19
      patients (26.8 %), and 4 cases (5.6 %) got worse. Five patients (7.0 %) were
      unassessable for efficacy. The common adverse events were visual disturbances (17
      patients, 23.9 %), abnormal liver function test results (12 patients, 16.9 %),
      adverse psychological effects (3 patients, 4.2 %), and others (10 patients, 14.0
      %). Treatment with voriconazole had to be stopped in 2 cases (2.8 %) because of
      serious adverse events (abnormal liver function test results). There was no
      association between adverse effects and trough voriconazole levels in serum.
      CONCLUSIONS: In Japan, voriconazole provides effective therapy of CPA in non
      immunocompromised patients with an acceptable level of toxicity.

PMID- 22956474
TI  - Infective endocarditis in congenital heart disease: a frequent community-acquired
      complication.
AB  - BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with
      congenital heart disease (CHD). Epidemiology, etiology, and outcome in this group
      are different to those of patients with acquired heart disease. METHODS: We
      reviewed all cases of proven and probable IE (Duke's criteria) diagnosed in our
      center during the last two decades. RESULTS: We observed 45 cases of IE in
      patients with CHD (age range 8 months to 35 years); these represented 5.5 % of
      all the episodes of IE in our institution during the study period. The most
      frequent CHD were ventricular septal defect (31 %), tetralogy of Fallot (19 %),
      and atrioventricular septal defect (11 %). Twenty cases of IE (44 %) were
      recorded in patients with non-corrected native-valve CHD. Of the 24 patients with
      prosthetic-valve IE, post-operative acquisition during the first 6 months was
      confirmed in 11 patients (range 4-110 days). IE was community-acquired in 62 % of
      cases. Streptococcus spp. were the most frequent etiologic agents (33 %),
      followed by Staphylococcus spp. (32 %). Surgery was required to treat IE in 47 %
      of patients (52 % in prosthetic-valve IE and 41 % in native-valve IE, p = ns). In
      comparison to native-valve IE, prosthetic-valve IE was significantly more
      nosocomial-acquired (61 vs. 14 %, p = 0.002), presented a higher heart failure
      rate at diagnosis (39 vs. 9 %, p = 0.035), and developed more breakthrough
      bacteremia episodes (19 vs. 0 %, p = 0.048). Global mortality was 24 % (75 % in
      patients with prosthetic-valve IE who required surgery and 0 % in patients with
      native-valve IE who required surgery, p = 0.001). Multivariate analysis excluding
      breakthrough bacteremia (100 % mortality in this condition) confirmed that
      nosocomial IE [odds ratio (OR), 23.7; 95 % confidence interval (CI), 2.3-239.9]
      and the presence of heart failure at diagnosis of IE (OR, 25.9; 95 % CI, 2.5
      269.6) were independent factors associated with mortality. CONCLUSION: Half of
      all cases of IE in patients with CHD occurred in patients with non-corrected
      native-valve CHD and two-thirds were community-acquired. Streptococcus spp. were
      the most frequent etiological agents. Patients with prosthetic-valve IE present a
      worse outcome, especially those requiring surgery. Breakthrough bacteremia,
      nosocomial IE, and heart failure are independent factors of mortality in patients
      with CHD presenting IE.

PMID- 22956475
TI  - The interaction between piperacillin-tazobactam and Aspergillus galactomannan
      antigenemia assay: is the story over?

PMID- 22956476
TI  - Evaluation of a catenary PBPK model for predicting the in vivo disposition of
      mAbs engineered for high-affinity binding to FcRn.
AB  - Efforts have been made to extend the biological half-life of monoclonal antibody
      drugs (mAbs) by increasing the affinity of mAb-neonatal Fc receptor (FcRn)
      binding; however, mixed results have been reported. One possible reason for a
      poor correlation between the equilibrium affinity of mAb-FcRn binding and mAb
      systemic pharmacokinetics is that the timecourse of endosomal transit is too
      brief to allow binding to reach equilibrium. In the present work, a new
      physiologically based pharmacokinetic (PBPK) model has been developed to
      approximate the pH and time-dependent endosomal trafficking of immunoglobulin G
      (IgG). In this model, a catenary sub-model was utilized to describe the endosomal
      transit of IgG and the time dependencies in IgG-FcRn association and
      dissociation. The model performs as well as a previously published PBPK model,
      with assumed equilibrium kinetics of mAb-FcRn binding, in capturing the
      disposition profile of murine mAb from wild-type and FcRn knockout mice (catenary
      vs. equilibrium model: r (2), 0.971 vs. 0.978; median prediction error, 3.38% vs.
      3.79%). Compared to the PBPK model with equilibrium binding, the present catenary
      PBPK model predicts much more moderate changes in half-life with altered FcRn
      binding. For example, for a 10-fold increase in binding affinity, the catenary
      model predicts <2.5-fold change in half-life compared to an ~8-fold increase as
      predicted by the equilibrium model; for a 100-fold increase in binding affinity,
      the catenary model predicts ~7-fold change in half-life compared to >70-fold
      increase as predicted by the equilibrium model. Predictions of the new catenary
      PBPK model are more consistent with experimental results in the published
      literature.

PMID- 22956477
TI  - Characterising lipid lipolysis and its implication in lipid-based formulation
      development.
AB  - Facing the increasing number of poorly water-soluble drugs, pharmaceutical
      scientists are required to break new grounds for the delivery of these
      pharmaceutically problematic drugs. Lipid-based drug delivery systems (LBDDS)
      have received increased interest as a novel drug delivery platform during the
      last decades and several successfully marketed products have shown the potential
      for LBDDS. However, there exists a discrepancy between the clear need for
      innovative delivery forms and their rational design. In the case of LBDDS, this
      can be attributed to the complexity of LBDDS after administration. Unlike
      conventional formulations, LBDDS are susceptible to digestion in the
      gastrointestinal tract, the interplay of delivery system, drug and physiology
      ultimately effecting drug disposition. In vitro lipolysis has become an important
      technique to mimic the enzymatic degradation. For the better understanding of how
      LBDDS promote drug delivery, in vitro lipolysis requires advanced
      characterisation methods. In this review, the physiological background of lipid
      digestion is followed by a thorough summary of the techniques that are currently
      used to characterise in vitro lipolysis. It would be desirable that the
      increasing knowledge about LBDDS will foster their rationale development thereby
      increasing their broader application.

PMID- 22956479
TI  - Changes in occipital lobe gyrification may be an early marker for psychosis in
      youth with velo-cardio-facial syndrome.

PMID- 22956478
TI  - Pharmacokinetics and tissue disposition of lenalidomide in mice.
AB  - Lenalidomide is a synthetic derivative of thalidomide exhibiting multiple
      immunomodulatory activities beneficial in the treatment of several hematological
      malignancies. Murine pharmacokinetic characterization necessary for translational
      and further preclinical investigations has not been published. Studies herein
      define mouse plasma pharmacokinetics and tissue distribution after intravenous
      (IV) bolus administration and bioavailability after oral and intraperitoneal
      delivery. Range finding studies used lenalidomide concentrations up to 15 mg/kg
      IV, 22.5 mg/kg intraperitoneal injections (IP), and 45 mg/kg oral gavage (PO).
      Pharmacokinetic studies evaluated doses of 0.5, 1.5, 5, and 10 mg/kg IV and 0.5
      and 10 mg/kg doses for IP and oral routes. Liquid chromatography-tandem mass
      spectrometry was used to quantify lenalidomide in plasma, brain, lung, liver,
      heart, kidney, spleen, and muscle. Pharmacokinetic parameters were estimated
      using noncompartmental and compartmental methods. Doses of 15 mg/kg IV, 22.5
      mg/kg IP, and 45 mg/kg PO lenalidomide caused no observable toxicity up to 24 h
      postdose. We observed dose-dependent kinetics over the evaluated dosing range.
      Administration of 0.5 and 10 mg/kg resulted in systemic bioavailability ranges of
      90-105% and 60-75% via IP and oral routes, respectively. Lenalidomide was
      detectable in the brain only after IV dosing of 5 and 10 mg/kg. Dose-dependent
      distribution was also observed in some tissues. High oral bioavailability of
      lenalidomide in mice is consistent with oral bioavailability in humans. Atypical
      lenalidomide tissue distribution was observed in spleen and brain. The observed
      dose-dependent pharmacokinetics should be taken into consideration in
      translational and preclinical mouse studies.

PMID- 22956480
TI  - Review: adverse effects of different second-generation antipsychotics vary in
      children and adolescents.

PMID- 22956481
TI  - No difference in extrapyramidal side effects between first-generation and second
      generation antipsychotics.

PMID- 22956482
TI  - Adding facilitated physical activity to standard GP care for depression does not
      improve symptoms.

PMID- 22956483
TI  - Review: urgent need for RCT evidence on effectiveness of crisis interventions for
      borderline personality disorder.

PMID- 22956484
TI  - Comparative virulence of clinical Brachyspira spp. isolates in inoculated pigs.
AB  - Classical swine dysentery is associated with the presence of the strongly beta
      hemolytic Brachyspira hyodysenteriae. However, multiple Brachyspira spp. can
      colonize the porcine colon. Since 2008, several Brachyspira spp. not identified
      as B. hyodysenteriae by genotypic and/or phenotypic methods have been isolated
      from the feces of pigs with clinical disease typical of swine dysentery. In the
      current study, 8 clinical isolates, including 5 strongly beta-hemolytic and 3
      weakly beta-hemolytic Brachyspira strains, and a reference strain of B.
      hyodysenteriae (B204) were inoculated into pigs (n = 6 per isolate) to compare
      pathogenic potential following oral inoculation. Results revealed that strongly
      beta-hemolytic isolates induced significantly greater typhlocolitis than those
      that are weakly beta-hemolytic, regardless of the genetic identification of the
      isolate, and that strongly beta-hemolytic isolates identified as "Brachyspira sp.
      SASK30446" and Brachyspira intermedia by polymerase chain reaction (PCR) produced
      lesions similar to those caused by B. hyodysenteriae. The results suggest that
      phenotypic culture characteristics of Brachyspira spp. may be a more sensitive
      indicator of potential to induce dysentery-like disease in pigs than molecular
      identification alone based on currently available PCR assays. Additionally,
      culture of mucosal scrapings obtained at necropsy was more sensitive than direct
      PCR on the same samples for detection of Brachyspira spp.

PMID- 22956485
TI  - Bronchopneumonia in two dairy calves associated with Mannheimia species cluster V
      infection.
AB  - The pathological, bacteriological, and molecular findings of two 3-week-old
      Holstein calves with bronchopneumonia are presented. Heavy pure growth of a
      Mannheimia species most closely aligned with the unnamed cluster V strains on the
      basis of 16S ribosomal RNA sequencing was detected in the lungs of both calves in
      association with Bovine respiratory syncytial virus infection. While Mannheimia
      species closely related to cluster V strains have occasionally been reported in
      association with pneumonia, meningitis, and abortion in cattle, the current
      report provides a description of the gross and histopathological lesions produced
      by a cluster V strain of Mannheimia species. Lesions in the lung were found to be
      typical of those described for Mannheimia haemolytica with the absence of areas
      of coagulation necrosis rimmed by leukocytes and more pronounced intra-alveolar
      hemorrhage. Lesions were linked to the presence of leukotoxin A based on
      phenotypic hemolysis and molecular demonstration of the leukotoxin A gene.

PMID- 22956486
TI  - Comparative analysis of serotonin in equine plasma with liquid chromatography-
      tandem mass spectrometry and enzyme-linked immunosorbent assay.
AB  - Serotonin is regularly measured in equine platelet-poor plasma in research
      settings. However, reported reference values vary between studies, partially
      because plasma serotonin concentrations are very low and a reliable and
      affordable detection method is lacking. A simple, rapid, and sensitive method for
      serotonin determination in equine platelet-poor plasma using liquid
      chromatography--tandem mass spectrometry (LC-MS/MS) was developed and validated.
      Results of a commercially available enzyme-linked immunosorbent assay (ELISA)
      were compared to the LC-MS/MS results, in order to validate a test more suitable
      for use in a clinical situation. For LC-MS/MS, 500 ul of plasma was required, and
      deuterated serotonin was used as an internal standard. The sample preparation was
      based upon a simple liquid extraction into ethyl acetate. Chromatographic
      separation was performed with an acetic acid--acetonitrile mobile phase gradient
      elution. Linearity was demonstrated between 3 ng/ml and 100 ng/ml. A limit of
      quantification of 3 ng/ml was achieved, corresponding to a limit of detection of
      0.10 ng/ml. Comparison of LC-MS/MS and ELISA with Passing-Bablok regression and
      Bland--Altman plotting showed a poor agreement between the 2 methods, with an
      increasing difference within the higher range of measurements. Caution is needed
      when extrapolating results from sources using different analytical techniques.

PMID- 22956487
TI  - Detection and molecular characterization of Porcine astrovirus strains associated
      with swine diarrhea.
AB  - Astrovirus has been reported to be associated with diarrhea in pigs. The current
      study was conducted for the detection and molecular characterization of
      astroviruses in diarrheic pigs submitted to the Veterinary Diagnostic Laboratory,
      University of Minnesota. Intestinal contents from 269 pigs were examined by
      reverse transcription polymerase chain reaction (RT-PCR), and 62% were found
      positive for astroviruses. Of the positive samples, 20% were positive for
      astrovirus alone while astrovirus with rotavirus was detected in 58% of the
      samples. The remaining 22% revealed the presence of astrovirus along with Porcine
      hemagglutinating encephalomyelitis virus, Transmissible gastroenteritis virus, or
      Porcine circovirus-2. Sequencing the capsid gene of 56 randomly selected samples
      confirmed them to be Porcine astrovirus type 4 (PAstV-4) with 58-100% nucleotide
      identity within these viruses. Phylogenetic analysis revealed 2 possible
      subgroups. The results indicate that PAstV is present on swine farms in the
      United States and that it may be associated with diarrhea either alone or in
      combination with other enteric viruses. Further studies are needed to determine
      strain diversity among porcine astroviruses so that appropriate control
      strategies can be devised and implemented.

PMID- 22956488
TI  - Activation of Aicda gene transcription by Pax5 in plasmacytoma cells.
AB  - Activation-induced deaminase (AID) is an enzyme responsible for somatic
      hypermutation and immunoglobulin heavy chain class switch recombination. Because
      AID causes double-stranded breaks in DNA, its expression is highly regulated and
      is normally restricted to germinal-center B cells. Dysregulated AID expression
      can lead to cancer as a result of AID-mediated chromosomal translocations. Many
      transcription factors including paired box protein 5 (Pax5) have been implicated
      in regulating the expression of Aicda, the gene encoding AID. In this study, we
      demonstrate that exogenous expression of Pax5 in a murine plasmacytoma cell line,
      558LMUM, leads to robust activation of endogenous Aicda transcription. Pax5 is
      known to initiate transcription through both its N-terminal-paired DNA-binding
      domain and its C-terminal-activation domain. Through mutational analysis, we
      demonstrate that Pax5 regulates Aicda transcription through its C-terminal
      activation domain. Together, our work describes a novel system that will be
      useful for determining how Pax5 regulates Aicda transcription.

PMID- 22956490
TI  - Clinical and economic burden of opioid use for postsurgical pain: focus on
      ventilatory impairment and ileus.
AB  - Opioid-related adverse drug events (ORADEs) can have a significant impact on
      patient recovery after surgery. This review investigates the impact of two
      ORADEs, respiratory depression and postoperative ileus (POI), on clinical and
      economic outcomes. Opioid-induced ventilatory impairment is a potentially serious
      ORADE that can result in apnea and even death. The incidence of ventilatory
      impairment is approximately 1%, even among patients receiving opioids using
      patient-controlled analgesia. Costs are increased in patients treated with
      opioids who are at high risk of ventilatory impairment due to the need for more
      intensive monitoring from nursing staff and the use of alarmed monitoring
      equipment. Opioids, together with other factors, contribute to the development of
      POI through a direct effect on gut motility. Postoperative ileus has been shown
      to significantly increase hospital length of stay and cost of care. A key
      determinant of ileus development, as well as length of stay and costs, is
      postsurgical opioid dose. Data from a retrospective analysis show that a daily
      hydromorphone dose of 2 mg/day markedly increases the risk of POI. In addition,
      although the incidence of POI is reduced in patients who undergo laparoscopic
      surgery or hand-assisted laparoscopic surgery compared with open surgery, the
      reduction of POI can potentially be negated by excessive opioid use. Therefore,
      multimodal, opioid-sparing strategies should be explored and used to reduce
      severe ORADEs and improve outcomes in the surgical setting.

PMID- 22956491
TI  - Liposomal bupivacaine: an innovative nonopioid local analgesic for the management
      of postsurgical pain.
AB  - Local anesthetics are a cornerstone of multimodal pain control strategies in the
      surgical setting as they have a long history of use and an established safety
      profile. Although effective, their duration of action is relatively short, which
      usually leads to the use of other agents, such as opioids, for effective
      postsurgical pain control in most patients. A medical need exists to extend the
      duration of analgesia with local anesthetics to help reduce the reliance on
      opioids in the postsurgical setting. Liposomal bupivacaine uses a product
      delivery platform to release bupivacaine slowly over 96 hours after infiltration
      at the surgical site. Liposomal bupivacaine was compared with placebo in two
      pivotal, multicenter, randomized, double-blind, parallel-group trials in 189
      adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults
      undergoing orthopedic surgery (bunionectomy). Among patients undergoing
      hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain
      scores for up to 72 hours (primary end point) as measured by the area under the
      curve of pain scores on the numeric rating scale (p<0.0001), reduced overall
      opioid consumption (p <= 0.0006), increased the proportion of patients who did
      not receive opioids (p<0.0008), delayed time to first opioid by more than 13
      hours (p<0.0001), and was associated with significantly higher rates of patient
      satisfaction (p=0.0007) compared with placebo. Similarly, in patients undergoing
      bunionectomy, liposomal bupivacaine significantly reduced total consumption of
      rescue opioids (p=0.0077) and cumulative pain scores as measured by the area
      under the curve of pain scores on the numeric rating scale (p=0.0005) during the
      first 24 postsurgical hours (primary end point) relative to placebo. Furthermore,
      liposomal bupivacaine also significantly delayed the time to first use of opioid
      rescue (p<0.0001) and increased the proportion of patients requiring no rescue
      opioid treatment (p <= 0.0404) compared with placebo. The most common adverse
      events with liposomal bupivacaine were nausea, vomiting, and constipation. No
      adverse effects on the QTc interval or cardiac safety signal have been detected
      in the clinical trial development program (823 patients) when liposomal
      bupivacaine was infiltrated into the surgical site. The beneficial effects of
      liposomal bupivacaine on postsurgical pain management and opioid use,
      significantly reducing both, are likely to translate into improved clinical and
      economic outcomes.

PMID- 22956492
TI  - New directions in the management of postsurgical pain. Introduction.

PMID- 22956489
TI  - The role of activation-induced deaminase in antibody diversification and genomic
      instability.
AB  - More than a decade ago, activation-induced deaminase (AID) was identified as the
      initiator for somatic hypermutation (SHM) and class switch recombination (CSR).
      Since then, tremendous progress has been achieved toward elucidating how AID
      functions. AID targets the highly repetitive switch regions of the immunoglobulin
      heavy chain (IgH) locus to induce DNA double-strand breaks (DSBs), which can be
      rejoined, leading to switch of constant regions of antibody. When targeting to
      variable region exons of IgH and IgL loci, AID predominantly induces point
      mutations, termed SHM, resulting in increased affinity of antibody for antigen.
      While SHM and CSR enhance antibody diversity, AID-initiated DSBs and mutations
      may predispose B cells to carcinogenesis. This review focuses on the mechanisms
      that provide the specificity of AID targeting to Ig loci and the role of AID in
      genomic instability.

PMID- 22956493
TI  - Challenges in the management of acute postsurgical pain.
AB  - The majority of patients who undergo surgery will require drug therapy for the
      management of acute postsurgical pain. Effective control of acute postsurgical
      pain is essential for the patient not only in the short term but also in the long
      term to prevent the development of chronic pain, which can occur if early acute
      pain is prolonged. Currently, opioid analgesics are widely used for the
      management of acute postsurgical pain. Although opioids provide effective
      postsurgical pain relief, their use is associated with a number of risks,
      including the development of opioid-related adverse drug events (ORADEs). This
      review investigates the prevalence of opioid use in the postsurgical setting, the
      incidence of ORADEs, and the impact of these ORADEs on patient outcomes, length
      of stay, and costs after common surgeries. According to a national analysis of
      ORADE incidence, almost 20% of patients treated with opioids experienced an
      ORADE, with the most common being gastrointestinal effects, central nervous
      system effects, pruritus, or urinary retention. Studies show that the risk of
      developing an ORADE is higher in patients receiving higher doses of opioids and
      in patients undergoing orthopedic or gynecologic surgery compared with patients
      undergoing general surgery. Elderly patients and those with comorbidities (e.g.,
      obesity, sleep apnea, respiratory disease, urinary disorders) may be particularly
      vulnerable to ORADE development. Both hospital costs and length of stay are
      increased in patients with an ORADE versus those without an ORADE. Strategies to
      reduce the use of opioids after surgery are likely to result in positive outcomes
      by reducing the incidence of ORADEs and, as a result, reducing treatment costs
      associated with surgery and improving patient care.

PMID- 22956495
TI  - DNA hypomethylation and hemimethylation in cancer.
AB  - In contrast to earlier views that there was much compartmentalization of the
      types of sequences subject to cancer-linked changes in DNA epigenetics, it is now
      clear that both cancer-associated DNA hypomethylation and hypermethylation are
      found throughout the genome. The hypermethylation includes promoters of tumor
      suppressor genes whose expression becomes repressed, thereby facilitating cancer
      formation. How hypomethylation contributes to carcinogenesis has been less clear.
      Recent insights into tissue-specific intra- and intergenic methylation and into
      cancer methylomes suggest that some of the DNA hypomethylation associated with
      cancers is likely to aid in tumor formation and progression by many different
      pathways, including effects on transcription in cis. Cancer-associated loss of
      DNA methylation from intergenic enhancers, promoter regions, silencers, and
      chromatin boundary elements may alter transcription rates. In -addition, cancer
      associated intragenic DNA hypomethylation might modulate -alternative promoter
      usage, -production of intragenic noncoding RNA transcripts, cotranscriptional
      splicing, and transcription initiation or elongation. Initial studies of
      hemimethylation of DNA in cancer and many new studies of DNA demethylation in
      normal tissues suggest that active demethylation with spreading of
      hypomethylation can explain much of the cancer-associated DNA hypomethylation.
      The new discoveries that genomic 5-hydroxymethylcytosine is an intermediate in
      DNA demethylation, a base with its own functionality, and a modified base that,
      like 5-methylcytosine, exhibits cancer-associated losses, suggest that both
      decreased hydroxymethylation and decreased methylation of DNA play important
      roles in carcinogenesis.

PMID- 22956496
TI  - Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian
      development and cancer.
AB  - 5-Hydroxymethylcytosine (5hmC) is an oxidative product of 5-methylcytosine (5mC),
      catalyzed by the ten eleven translocation (TET) family of enzymes. Although 5hmC
      was discovered several decades ago, it was only after its recent identification
      in murine brain and stem cell DNA that it has become a major focus of epigenomic
      research. Part of the reason for this delay is due to the difficulty in detecting
      both global and locus-specific 5hmC levels. Several studies have addressed this
      issue with the development of novel techniques to locate and measure 5hmC, which
      led to multiple reports detailing 5hmC patterns in stem cells and global 5hmC
      levels during embryogenesis. Based on these studies of 5hmC levels and reports of
      tissue-specific TET expression, these enzymes are thought to play a role in
      mammalian development and differentiation. In addition, the TET enzymes are
      mutated in several types of cancer, affecting their activity and likely altering
      genomic 5hmC and 5mC patterns. Furthermore, oxidation of 5mC appears to be a step
      in several active DNA demethylation pathways, which may be important for normal
      processes, as well as global hypomethylation during cancer development and
      progression. Much has been revealed about this interesting DNA modification in
      recent years, but more research is needed for understanding the role of TET
      proteins and 5hmC in gene regulation and disease.

PMID- 22956497
TI  - Altered histone modifications in cancer.
AB  - In human health and disease the choreographed actions of a wide armory of
      transcription factors govern the regulated expression of coding and nonprotein
      coding genes. These actions are central to human health and are evidently
      aberrant in cancer. Central components of regulated gene expression are a variety
      of epigenetic mechanisms that include histone modifications. The post
      translational modifications of histones are widespread and diverse, and appear to
      be spatial--temporally regulated in a highly intricate manner. The true
      functional consequences of these patterns of regulation are still emerging.
      Correlative evidence supports the idea that these patterns are distorted in
      malignancy on both a genome-wide and a discrete gene loci level. These patterns
      of distortion also often reflect the altered expression of the enzymes that
      control these histone states. Similarly gene expression patterns also appear to
      reflect a correlation with altered histone modifications at both the candidate
      loci and genome-wide level. Clarity is emerging in resolving these relationships
      between histone modification status and gene expression -patterns. For example,
      altered transcription factor interactions with the key co-activator and co
      repressors, which in turn marshal many of the histone-modifying enzymes, may
      distort regulation of histone modifications at specific gene loci. In turn these
      aberrant transcriptional processes can trigger other altered epigenetic events
      such as DNA methylation and underline the aberrant and specific gene expression
      patterns in cancer. Considered in this manner, altered expression and recruitment
      of histone-modifying enzymes may underline the distortion to transcriptional
      responsiveness observed in malignancy. Insight from understanding these processes
      addresses the challenge of targeted epigenetic therapies in cancer.

PMID- 22956494
TI  - DNA methyltransferases, DNA damage repair, and cancer.
AB  - The maintenance DNA methyltransferase (DNMT) 1 and the de novo methyltransferases
      DNMT3A and DNMT3B are all essential for mammalian development. DNA methylation,
      catalyzed by the DNMTs, plays an important role in maintaining genome stability.
      Aberrant expression of DNMTs and disruption of DNA methylation patterns are
      closely associated with many forms of cancer, although the exact mechanisms
      underlying this link remain elusive. DNA damage repair systems have evolved to
      act as a genome-wide surveillance mechanism to maintain chromosome integrity by
      recognizing and repairing both exogenous and endogenous DNA insults. Impairment
      of these systems gives rise to mutations and directly contributes to
      tumorigenesis. Evidence is mounting for a direct link between DNMTs, DNA
      methylation, and DNA damage repair systems, which provide new insight into the
      development of cancer. Like tumor suppressor genes, an array of DNA repair genes
      frequently sustain promoter hypermethylation in a variety of tumors. In addition,
      DNMT1, but not the DNMT3s, appear to function coordinately with DNA damage repair
      pathways to protect cells from sustaining mutagenic events, which is very likely
      through a DNA methylation-independent mechanism. This chapter is focused on
      reviewing the links between DNA methylation and the DNA damage response.

PMID- 22956498
TI  - Nucleosome occupancy and gene regulation during tumorigenesis.
AB  - Nucleosomes are the basic structural units of eukaryotic chromatin. In recent
      years, it has become evident that nucleosomes and their position, in concert with
      other epigenetic mechanisms (such as DNA methylation, histone modifications,
      changes in histone variants, as well as small noncoding regulatory RNAs) play
      essential roles in the control of gene expression. Here, we discuss the
      mechanisms and factors that regulate nucleosome position and gene expression in
      normal and cancer cells.

PMID- 22956499
TI  - Epigenetic regulation of miRNAs in cancer.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs with gene regulatory functions. It
      has been demonstrated that the genes encoding for miRNAs undergo the same
      regulatory epigenetic processes of protein coding genes. In turn, a specific
      subgroup of miRNAs, called epi-miRNAs, is able to directly target key enzymatic
      effectors of the epigenetic machinery (such as DNA methyltransferases, histone
      deacetylases, and polycomb genes), therefore indirectly affecting the expression
      of epigenetically regulated oncogenes and tumor suppressor genes. Also, several
      of the epigenetic drugs currently approved as anticancer agents affect the
      expression of miRNAs and this might explain part of their mechanism of action.
      This chapter focuses on the tight relationship between epigenetics and miRNAs and
      provides some insights on the translational implications of these findings,
      leading to the upcoming introduction of epigenetically related miRNAs in the
      treatment of cancer.

PMID- 22956500
TI  - DNA hypomethylation and activation of germline-specific genes in cancer.
AB  - DNA methylation, occurring at cytosines in CpG dinucleotides, is a potent
      mechanism of transcriptional repression. Proper genomic methylation -patterns
      become profoundly altered in cancer cells: both gains (hypermethylation) and
      losses (hypomethylation) of methylated sites are observed. Although DNA
      hypomethylation is detected in a vast majority of human tumors and affects many
      genomic regions, its role in tumor biology remains elusive. Surprisingly, DNA
      hypomethylation in cancer was found to cause the aberrant activation of only a
      limited group of genes. Most of these are normally expressed exclusively in
      germline cells and were grouped under the term "cancer-germline" (CG) genes. CG
      genes represent unique examples of genes that rely primarily on DNA methylation
      for their tissue-specific expression. They are also being exploited to uncover
      the mechanisms that lead to DNA hypomethylation in tumors. Moreover, as CG genes
      encode tumor-specific antigens, their activation in cancer highlights a direct
      link between epigenetic alterations and tumor immunity. As a result, clinical
      trials combining epigenetic drugs with anti-CG antigen vaccines are being
      considered.

PMID- 22956501
TI  - APC and DNA demethylation in cell fate specification and intestinal cancer.
AB  - Most cases of colon cancer are initiated by mutation or loss of the tumor
      suppressor gene adenomatous polyposis coli (APC). APC controls many cellular
      functions including intestinal cell proliferation, differentiation, migration,
      and polarity. This chapter focuses on the role of APC in regulating a recently
      identified DNA demethylase system, consisting of a cytidine deaminase and a DNA
      glycosylase. A global decrease in DNA methylation is known to occur soon after
      loss of APC; however, how this occurs and its contribution to tumorigenesis has
      been unclear. In the absence of wild-type APC, ectopic expression of the DNA
      demethylase system leads to the hypomethylation of specific loci, including
      intestinal cell fating genes, and stabilizes intestinal cells in an
      undifferentiated state. Further, misregulation of this system may influence the
      acquisition of subsequent genetic mutations that drive tumorigenesis.

PMID- 22956503
TI  - Epigenetic reprogramming of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent stem cells of mesodermal origin
      that can be isolated from various sources and induced into different cell types.
      Although MSCs possess immune privilege and are more easily obtained than
      embryonic stem cells, their propensity to tumorigenesis has not been fully
      explored. Epigenomic changes in DNA methylation and chromatin structure have been
      hypothesized to be critical in the determination of lineage-specific
      differentiation and tumorigenesis of MSCs, but this has not been formally proven.
      We applied a targeted DNA methylation method to methylate a Polycomb group
      protein-governed gene, Trip10, in MSCs, which accelerated the cell fate
      determination of MSCs. In addition, targeted methylation of HIC1 and RassF1A,
      both tumor suppressor genes, transformed MSCs into tumor stem cell-like cells.
      This new method will allow better control of the differentiation of MSCs and
      their use in downstream applications.

PMID- 22956502
TI  - Epigenetic changes during cell transformation.
AB  - Malignant cancer emerges from normal healthy cells in a multistep -process that
      involves both genetic and epigenetic lesions. Both genetic and environmental
      inputs participate in driving the epigenetic changes that occur during human
      carcinogenesis. The pathologic changes seen in DNA methylation and histone
      posttranslational modifications are complex, deeply intertwined, and act in
      concert to produce malignant transformation. To better understand the causes and
      consequences of the pathoepigenetic changes in cancer formation, a variety of
      experimentally tractable human cell line model systems that accurately reflect
      the molecular alterations seen in the clinical disease have been developed.
      Results from studies using these cell line model systems suggest that early
      critical epigenetic events occur in a stepwise fashion prior to cell
      immortalization. These epigenetic steps coincide with the cell's transition
      through well-defined cell proliferation barriers of stasis and telomere
      dysfunction. Following cell immortalization, stressors, such as environmental
      toxicants, can induce malignant transformation in a process in which the
      epigenetic changes occur in a smoother progressive fashion, in contrast to the
      stark stepwise epigenetic changes seen prior to cell immortalization. It is hoped
      that developing a clearer understanding of the identity, timing, and consequences
      of these epigenetic lesions will prove useful in future clinical applications
      that range from early disease detection to therapeutic intervention in malignant
      cancer.

PMID- 22956505
TI  - Blood-derived DNA methylation markers of cancer risk.
AB  - The importance of somatic epigenetic alterations in tissues targeted for
      carcinogenesis is now well recognized and considered a key molecular step in the
      development of a tumor. Particularly, alteration of gene-specific and genomic DNA
      methylation has been extensively characterized in tumors, and has become an
      attractive biomarker of risk due to its specificity and stability in human
      samples. It also is clear that tumors do not develop as isolated phenomenon in
      their target tissue, but instead result from altered processes affecting not only
      the surrounding cells and tissues, but other organ systems, including the immune
      system. Thus, alterations to DNA methylation profiles detectable in peripheral
      blood may be useful not only in understanding the carcinogenic process and
      response to environmental insults, but can also provide critical insights in a
      systems biological view of tumorigenesis. Research to date has generally focused
      on how environmental exposures alter genomic DNA methylation content in
      peripheral blood. More recent work has begun to translate these findings to
      clinically useful endpoints, by defining the relationship between DNA methylation
      alterations and cancer risk. This chapter highlights the existing research
      linking the environment, blood-derived DNA methylation alterations, and cancer
      risk, and points out how these epigenetic alterations may be contributing
      fundamentally to carcinogenesis.

PMID- 22956504
TI  - Environmental toxicants, epigenetics, and cancer.
AB  - Tumorigenesis, a complex and multifactorial progressive process of transformation
      of normal cells into malignant cells, is characterized by the accumulation of
      multiple cancer-specific heritable phenotypes triggered by the mutational and/or
      non-mutational (i.e., epigenetic) events. Accumulating evidence suggests that
      environmental and occupational exposures to natural substances, as well as man
      made chemical and physical agents, play a causative role in human cancer. In a
      broad sense, carcinogenesis may be induced through either genotoxic or non
      genotoxic mechanisms; however, both genotoxic and non-genotoxic carcinogens also
      cause prominent epigenetic changes. This review presents current evidence of the
      epigenetic alterations induced by various chemical carcinogens, including
      arsenic, 1,3-butadine, and pharmaceutical and biological agents, and highlights
      the potential for epigenetic changes to serve as markers for carcinogen exposure
      and cancer risk assessment.

PMID- 22956507
TI  - Epigenetic targeting therapies to overcome chemotherapy resistance.
AB  - It is now well established that epigenetic aberrations occur early in malignant
      transformation, raising the possibility of identifying chemopreventive compounds
      or reliable diagnostic screening using epigenetic biomarkers. Combinatorial
      therapies effective for the reexpression of tumor suppressors, facilitating
      resensitization to conventional chemotherapies, hold great promise for the future
      therapy of cancer. This approach may also perturb cancer stem cells and thus
      represent an effective means for managing a number of solid tumors. We believe
      that in the near future, anticancer drug regimens will routinely include
      epigenetic therapies, possibly in conjunction with inhibitors of "stemness"
      signal pathways, to effectively reduce the devastating occurrence of cancer
      chemotherapy resistance.

PMID- 22956506
TI  - Epigenetic therapies in MDS and AML.
AB  - The use of low dose hypomethylating agents for patients with myelodysplastic
      syndrome (MDS) and secondary acute myeloid leukemia (AML) has had made a
      significant impact. In the past, therapies for these diseases were limited and
      patients who elected to receive treatment were subject to highly toxic, inpatient
      chemotherapeutics, which were often ineffective. In the era of hypomethylating
      agents (azacitidine and decitabine), a patient with high grade MDS or AML with
      multilineage dysplasia can be offered the alternative of outpatient, relatively
      low-toxicity therapy. Despite the fact that CR (CR) rates to such agents remain
      relatively low at 15-20%, a much larger percentage of patients will have
      clinically significant improvements in hemoglobin, platelet, and neutrophil
      counts while maintaining good outpatient quality of life. As our clinical
      experience with azanucleotides expands, questions regarding patient selection,
      optimal dosing strategy, latency to best response and optimal duration of therapy
      following disease progression remain, but there is no question that for some
      patients these agents offer, for a time, an almost miraculous clinical benefit.
      Ongoing clinical trials in combination and in sequence with conventional
      therapeutics, with other epigenetically active agents, or in conjunction with
      bone marrow transplantation continue to provide promise for optimization of these
      agents for patients with myeloid disease. Although the mechanism(s) responsible
      for the proven efficacy of these agents remain a matter of some controversy,
      activity is thought to stem from induction of DNA hypomethylation, direct DNA
      damage, or possibly even immune modulation; there is no question that they have
      become a permanent part of the armamentarium against myeloid neoplasms.

PMID- 22956509
TI  - Circulating levels of interleukin-17 and cardiovascular outcomes in patients with
      acute myocardial infarction.
AB  - AIM: Interleukin (IL)-17 pathway is being clinically targeted in immune-mediated
      diseases, most of which are associated with a significant cardiovascular risk. We
      investigated the relationship between serum levels of IL-17 and the risk of
      cardiovascular events in patients with acute myocardial infarction. METHODS AND
      RESULTS: We used data from 981 patients enrolled in the prospective, multicentre
      French registry of Acute ST elevation, or non-ST-elevation Myocardial Infarction
      (Fast-MI, NCT00673036). Serum levels of IL-17 were associated with the risk of
      all-cause death and recurrent MI at 2 years, with levels of IL-17 below the
      median indicative of a worse outcome. The impact of IL-17 remained significant
      after adjustment for known cardiovascular risk factors, C-reactive protein, and
      treatments including statins: hazard ratio (HR) = 1.40 (1.03-1.91); P = 0.03. IL
      17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial
      vascular cell adhesion molecule (VCAM-1) expression. Patients with low (below the
      median) IL-17 levels and high (above the median) soluble VCAM-1 (sVCAM-1) levels
      were at particularly increased risk of death and MI: adjusted HR = 2.22 (1.32
      3.75) compared with the high IL-17/low sVCAM-1 group (P = 0.002). CONCLUSIONS:
      Low serum levels of IL-17 are associated with a higher risk of major
      cardiovascular events in Caucasian patients with acute MI. Our results raise
      possible concern about the use of inhibitors of the IL-17 pathway in clinical
      settings associated with a high cardiovascular risk. CLINICAL TRIALS
      REGISTRATION: NCT00673036.

PMID- 22956508
TI  - Methods for cancer epigenome analysis.
AB  - Accurate detection of epimutations in tumor cells is crucial for -understanding
      the molecular pathogenesis of cancer. Alterations in DNA methylation in cancer
      are functionally important and clinically relevant, but even this well-studied
      area is continually re-evaluated in light of unanticipated results, such as the
      strong association between aberrant DNA methylation in adult tumors and polycomb
      group profiles in embryonic stem cells, cancer-associated genetic mutations in
      epigenetic regulators such as DNMT3A and TET family genes, and the discovery of
      altered 5-hydroxymethylcytosine, a product of TET proteins acting on 5
      methylcytosine, in human tumors with TET mutations. The abundance and
      distribution of covalent histone modifications in primary cancer tissues relative
      to normal cells is an important but largely uncharted area, although there is
      good evidence for a mechanistic role of cancer-specific alterations in histone
      modifications in tumor etiology, drug response, and tumor progression. Meanwhile,
      the discovery of new epigenetic marks continues, and there are many useful
      methods for epigenome analysis applicable to primary tumor samples, in addition
      to cancer cell lines. For DNA methylation and hydroxymethylation, next-generation
      sequencing allows increasingly inexpensive and quantitative whole-genome
      profiling. Similarly, the refinement and maturation of chromatin
      immunoprecipitation with next-generation sequencing (ChIP-seq) has made possible
      genome-wide mapping of histone modifications, open chromatin, and transcription
      factor binding sites. Computational tools have been developed apace with these
      epigenome methods to better enable accurate interpretation of the profiling data.

PMID- 22956510
TI  - Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and
      LRRK2 in early-onset Parkinson's disease.
AB  - Approximately 3.6% of patients with Parkinson's disease develop symptoms before
      age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial
      recurrence risk than late-onset patients, and 3 main recessive EOPD genes have
      been described. We aimed to establish the prevalence of mutations in these genes
      in a UK cohort and in previous studies. We screened 136 EOPD probands from a high
      ascertainment regional and community-based prevalence study for pathogenic
      mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also
      carried out a systematic review, calculating the proportion of cases with
      pathogenic mutations in previously reported studies. We identified 5 patients
      with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate
      of mutations overall was 5.1%. Mutations were more common in patients with age at
      onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected
      sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation
      carriers were more likely to present with rigidity and dystonia, and 6 of 7
      mutation carriers had lower limb symptoms at onset. Our systematic review
      included information from >5800 unique cases. Overall, the weighted mean
      proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was
      8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian
      subjects. The overall frequency of mutations in known EOPD genes was lower than
      previously estimated. Our study shows an increased likelihood of mutations in
      patients with lower AAO, family history, or parental consanguinity.

PMID- 22956511
TI  - Endovascular repair of a Streptococcus pneumonia-induced aortitis complicated by
      an iliacocaval fistula.
AB  - PURPOSE: To describe the successful endovascular treatment and follow-up of a
      patient with a Streptococcus pneumonia-induced right iliacocaval fistula. CASE
      REPORT: A 82-year-old man was diagnosed with a right iliacocaval fistula, as a
      result of Streptococcus pneumoniae infection of the distal aorta and proximal
      right common iliac artery. After antibiotic treatment, he was initially
      unsuccessfully treated with balloon expandable covered stents. Then, the fistula
      was excluded by an aortamonoiliac endograft to the left common iliac artery, and
      occluders in the distal and proximal right common iliac artery followed by a
      femoral-femoral crossover bypass. Postoperatively patient was treated with
      prolonged antibiotics. After a follow-up of 20 months, there are no signs of
      active infection, endoleak, or fistula, both clinically and on 2-deoxy-2
      [F18]fluoro-D-glucose positron emission tomography/computed tomography.
      CONCLUSION: In selected patients, complicated infectious disease of the aorto
      iliac tract may be treated successfully with an endograft and prolonged
      antibiotics.

PMID- 22956512
TI  - Effect of preoperative aneurysm diameter on long-term survival after endovascular
      aortic aneurysm repair.
AB  - OBJECTIVE: To investigate the effect of aneurysm size on long-term survival after
      endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs). METHODS:
      Retrospective study of all consecutive patients treated with EVAR for AAA at a
      single institution. RESULTS: One hundred and nineteen patients (mean age 71,
      range 45-91) underwent EVAR during a 4-year period. The mean maximal aneurysm
      diameter was 58 mm (range 34-93 mm). Mean follow-up was 34 months (range 1-80).
      Cox regression analysis after controlling for age, renal function, coronary
      disease, and smoking showed a 4.9-fold higher risk of death for patients with
      preoperative aneurysm size >= 60 mm as compared to patients with aneurysm size
      <60 mm. No aneurysm-related deaths occurred during the follow-up. CONCLUSION:
      This present study provides evidence that aneurysm size >=60 mm is independently
      associated with worse survival during follow-up.

PMID- 22956513
TI  - Invited commentary: structural equation models and epidemiologic analysis.
AB  - In this commentary, structural equation models (SEMs) are discussed as a tool for
      epidemiologic analysis. Such models are related to and compared with other
      analytic approaches often used in epidemiology, including regression analysis,
      causal diagrams, causal mediation analysis, and marginal structural models.
      Several of these other approaches in fact developed out of the SEM literature.
      However, SEMs themselves tend to make much stronger assumptions than these other
      techniques. SEMs estimate more types of effects than do these other techniques,
      but this comes at the price of additional assumptions. Many of these assumptions
      have often been ignored and not carefully evaluated when SEMs have been used in
      practice. In light of the strong assumptions employed by SEMs, the author argues
      that they should be used principally for the purposes of exploratory analysis and
      hypothesis generation when a broad range of effects are potentially of interest.

PMID- 22956514
TI  - A structural equation modeling approach to fatigue-related risk factors for
      occupational injury.
AB  - Occupational injury is associated with numerous individual and work-related risk
      factors, including long working hours and short sleep duration; however, the
      complex mechanisms causing such injuries are not yet fully understood. The
      authors used structural equation modeling (SEM) as a novel approach to examine
      fatigue-related direct and indirect potential risk factors for occupational
      injury. The study sample contained 89,366 employed workers from the National
      Health Interview Survey (pooled across 6 years, 2004-2009), an annual survey of a
      representative cross-sectional sample of the US population. Direct and indirect
      effects of weekly hours worked and usual sleep duration on occupational injuries
      were modeled using SEM procedures for dichotomous outcomes and a complex sampling
      design. Confounding and mediating effects of gender, age, race/ethnicity,
      occupation, industry, type of pay, body mass index (BMI), and psychological
      distress were simultaneously examined. Long working hours and short sleep
      duration independently increased the risk of injury. Additional direct risk
      factors were gender, occupation, type of pay, and BMI. At the same time, sleep
      duration mediated the adverse relations of long working hours, high psychological
      distress, and high BMI with injury. These findings indicate that SEM is a useful
      approach with which to examine dichotomous outcomes and indirect effects in
      complex samples, and it offers a comprehensive new model of injury prediction.

PMID- 22956515
TI  - The authors respond to "structural equation models and epidemiologic analysis".

PMID- 22956516
TI  - cAMP-dependent regulation of ovulatory response genes is amplified by IGF1 due to
      synergistic effects on Akt phosphorylation and NF-kappaB transcription factors.
AB  - Granulosa cells play a crucial role as mediator of the LH-dependent ovulatory
      response. The intraovarian factor IGF1 is produced by ovarian somatic cells of
      healthy follicles during the ovulatory response. The objective of this study was
      to identify mechanisms by which IGF1, alone or in combination with LH, regulates
      the expression of genes in granulosa cells, which are crucial for ovulation. To
      achieve this objective, short-term, primary murine granulosa cell cultures were
      treated for 2-8  h with 1 mM 8-bromoadenosine 3',5'-cAMP to mimic the LH surge
      and/or 100  ng/ml IGF1. While cAMP induced significant increases in the
      expression of important ovulatory response genes including amphiregulin (Areg),
      epiregulin (Ereg), betacellulin (Btc), or interleukin 6 (Il6), IGF1 alone had no
      effect. However, co-treatment of cells with IGF1 and cAMP had a synergistic
      effect on Areg, Ereg, Btc, and Il6 mRNA abundance. Pretreatment of granulosa
      cells with the MEK1/2 inhibitor U0126 demonstrated that cAMP-dependent increases
      in Areg, Ereg, Btc, and Il6 were mediated by extracellular regulated kinase 1/2
      phosphorylation. However, western blot analyses coupled with pretreatment of
      cells with the PI3K inhibitor LY294002 indicated that the synergistic effect of
      cAMP and IGF1 on transcript levels was due in part to cooperative increases in
      Akt phosphorylation. Western blot analyses also demonstrated that IGF1 and the
      combined treatment of cAMP and IGF1 decreased NF-kappaB p65 phosphorylation and
      increased NF-kappaB p52 levels. Together, these data indicate that IGF1 may
      amplify cAMP-dependent regulation of ovulatory response gene expression above an
      important threshold level and therefore represents a novel role for IGF1 during
      ovulation.

PMID- 22956517
TI  - Genomic imprints as a model for the analysis of epigenetic stability during
      assisted reproductive technologies.
AB  - Gamete and early embryo development are important stages when genome-scale
      epigenetic transitions are orchestrated. The apparent lack of remodeling of
      differential imprinted DNA methylation during preimplantation development has
      lead to the argument that epigenetic disruption by assisted reproductive
      technologies (ARTs) is restricted to imprinted genes. We contend that aberrant
      imprinted methylation arising from assisted reproduction or infertility may be an
      indicator of more global epigenetic instability. Here, we review the current
      literature on the effects of ARTs, including ovarian stimulation, in vitro oocyte
      maturation, oocyte cryopreservation, IVF, ICSI, embryo culture, and infertility
      on genomic imprinting as a model for evaluating epigenetic stability.
      Undoubtedly, the relationship between impaired fertility, ARTs, and epigenetic
      stability is unquestionably complex. What is clear is that future studies need to
      be directed at determining the molecular and cellular mechanisms giving rise to
      epigenetic errors.

PMID- 22956518
TI  - Galectin-1 and galectin-3 in the corpus luteum of mice are differentially
      regulated by prolactin and prostaglandin F2alpha.
AB  - Galectin-1 and galectin-3, beta-galactoside-binding lectins, are specifically
      expressed in the regressing corpus luteum (CL) of mice; however, their function
      remains unclear. In this study, we examined the effects of prolactin (PRL) and
      prostaglandin F(2) (alpha) (PGF(2) (alpha)), two main regulatory molecules of
      mouse CL function, on galectin expression. In situ hybridization analysis clearly
      demonstrated an initial increase in galectin-1 in the newly formed CL (CLN) after
      postpartum ovulation 48  h after compulsory weaning. This was accompanied by a
      decline in 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and LH receptor (LH-R)
      expression, suggesting a withdrawal of PRL stimulation. At 72  h after the
      weaning, the expression of both galectins in CLN was remarkably increased, being
      associated with an intense expression of progesterone degradation enzyme (20alpha
      HSD). Compulsory weaning did not significantly alter both galectin expression in
      the remaining CL of pregnancy (CLP), while PGF(2) (alpha) strongly upregulated
      both galectin expression only in the remaining CLP, which lacked LH-R in
      postpartum mice. Administration of bromocriptine, an antagonist for PRL
      secretion, to nonpregnant cyclic mice induced an accumulation of galectin-1 - but
      not galectin-3 - in all CL of various generations, and additional PRL treatment
      reduced its accumulation, suggesting a direct suppressive effect of PRL on
      galectin-1 expression. Although the function and regulatory mechanism of galectin
      in the CL is not fully understood, PGF(2) (alpha) is an excellent candidate that
      regulates galectin expression, but its effect may be abolished by LH-R-mediated
      signal. PRL withdrawal seems to be necessary for an initiation of luteolysis and
      the following PGF(2) (alpha)-induced galectin expression.

PMID- 22956519
TI  - Differential actions of fibroblast growth factors on intracellular pathways and
      target gene expression in bovine ovarian granulosa cells.
AB  - Several fibroblast growth factors (FGFs), including FGF1, FGF4 and FGF10, alter
      ovarian granulosa cell function. These ligands exhibit different patterns of
      receptor activation, and their mechanisms of action on granulosa cells remain
      unknown. The objective of this study was to identify the major pathways and
      target genes activated by FGF1, FGF4 and FGF10 in primary oestrogenic granulosa
      cells cultured under serum-free conditions. FGF1 and FGF4 increased levels of
      mRNA encoding Sprouty family members, SPRY2 and SPRY4, and the orphan nuclear
      receptors NR4A1 and NR4A3. Both FGF1 and FGF4 decreased levels of mRNA encoding
      SPRY3 and the pro-apoptotic factor BAX. FGF1 but not FGF4 stimulated expression
      of the cell cycle regulator, GADD45B. In contrast, FGF10 altered the expression
      of none of these genes. Western blot demonstrated that FGF4 activated ERK1/2 and
      Akt signalling rapidly and transiently, whereas FGF10 elicited a modest and
      delayed activation of ERK1/2. These data show that FGF1 and FGF4 activate typical
      FGF signalling pathways in granulosa cells, whereas FGF10 activates atypical
      pathways.

PMID- 22956520
TI  - Effects of oxygen concentration on in vitro maturation of canine oocytes in a
      chemically defined serum-free medium.
AB  - Canine oocytes require an extended period of culture (72  h) in vitro for nuclear
      maturation to the metaphase II stage, which also results in high degeneration.
      Canine cumulus oocyte complexes were isolated by slicing from ovaries collected
      after ovariohysterectomy and cultured in serum-free synthetic oviductal fluid
      incubated at low (5%) or high (20%) oxygen levels. Changes in oocyte nuclear
      maturation rates, H(2)O(2) levels within the oocytes and mRNAs of reactive oxygen
      species inhibitory genes superoxide dismutase 1 and 2 (SOD1 and 2), glutathione
      reductase (GSR), glutathione peroxidase (GPX1), and catalase (CAT) were
      quantified. Higher meiotic resumption from germinal vesicle breakdown up to MII
      was observed in low O(2) (41.8+/-13.1%) compared to high O(2) (15.8+/-8.2%)
      (P=0.014) after 52  h of culture (n=112). Extension of the culture period up to
      84  h at low O(2) (n=457 oocytes) produced the highest meiotic resumption at 72 
      h (64.1+/-6.0%; P=0.008), compared with 52  h. Oocytes (n=110) cultured in high
      O(2) contained higher levels of peroxidase measured using the 2',7'
      dichlorodihydrofluorescein diacetate fluorescence assay after 72  h of culture
      compared with low O(2) (P=0.004). High O(2)-cultured oocytes also showed higher
      amounts of SOD1, SOD2, GSR, GPX1, and CAT mRNA. Vitamin E in high oxygen level
      was able to decrease degeneration (P=0.008) but had no improving effect on
      percentage of oocytes in MII. These results for the first time showed that low
      oxygen gas composition improves nuclear maturation rates and alleviates the
      oxidative stress for canine oocytes during in vitro maturation.

PMID- 22956521
TI  - The clinical value of computer tomographic angiography for the diagnosis and
      therapeutic planning of patients with pulmonary sequestration.
AB  - OBJECTIVES: This study was conducted to evaluate the clinical value of computed
      tomographic (CT) angiography for diagnosis and therapeutic planning in patients
      with pulmonary sequestration. METHODS: Forty-three patients with suspected
      pulmonary sequestration underwent CT angiography before undergoing digital
      subtraction angiography or surgery. For each patient, CT angiography was used to
      determine whether the pulmonary sequestration was suitable for coil embolization,
      surgical resection or conservative treatment. The treatments planned using CT
      angiography were compared with actual treatment decisions made or treatments
      administered using digital subtraction angiography or surgery. RESULTS: Digital
      subtraction angiography and/or surgery confirmed pulmonary sequestration in 37
      patients; six patients had no pulmonary sequestration. The diagnostic performance
      of CT angiography for pulmonary sequestration in the patient-based evaluation
      yielded an accuracy of 97.7%, sensitivity of 97.3%, specificity of 100%, positive
      predictive value (PPV) of 100% and negative predictive value (NPV) of 85.7%. The
      aberrant systemic artery-based evaluation yielded an accuracy of 98.0%,
      sensitivity of 97.8%, specificity of 100%, PPV of 100% and NPV of 85.7%.
      Treatments could be correctly planned using CT angiography with 100% accuracy,
      sensitivity, specificity, PPV and NPV according to the aneurysm-based evaluation.
      CONCLUSIONS: We have obtained promising results with a CT angiography-based
      protocol, rather than a digital subtraction angiography-based protocol, as the
      only diagnostic and pretreatment planning tool in patients with pulmonary
      sequestration. The CT angiography-based selection of treatment strategies seems
      to be safe and effective in the majority of patients with pulmonary
      sequestration.

PMID- 22956522
TI  - Reducing the prevalence of chronic post-thoracotomy pain syndrome: is total
      intravenous anaesthesia superior to inhalation anaesthesia?

PMID- 22956523
TI  - Study on characteristics of printed circuit board liberation and its crushed
      products.
AB  - Recycling printed circuit board waste (PCBW) waste is a hot issue of
      environmental protection and resource recycling. Mechanical and thermo-chemical
      methods are two traditional recycling processes for PCBW. In the present
      research, a two-step crushing process combined with a coarse-crushing step and a
      fine-pulverizing step was adopted, and then the crushed products were classified
      into seven different fractions with a standard sieve. The liberation situation
      and particle shape in different size fractions were observed. Properties of
      different size fractions, such as heating value, thermogravimetric, proximate,
      ultimate and chemical analysis were determined. The Rosin-Rammler model was
      applied to analyze the particle size distribution of crushed material. The
      results indicated that complete liberation of metals from the PCBW was achieved
      at a size less than 0.59 mm, but the nonmetal particle in the smaller-than-0.15
      mm fraction is liable to aggregate. Copper was the most prominent metal in PCBW
      and mainly enriched in the 0.42-0.25 mm particle size. The Rosin-Rammler equation
      adequately fit particle size distribution data of crushed PCBW with a correlation
      coefficient of 0.9810. The results of heating value and proximate analysis
      revealed that the PCBW had a low heating value and high ash content. The
      combustion and pyrolysis process of PCBW was different and there was an obvious
      oxidation peak of Cu in combustion runs.

PMID- 22956524
TI  - Induced senescence: a cunning Fox's new trick.

PMID- 22956525
TI  - Has the T cell bitten off more than it can chew?

PMID- 22956526
TI  - MDS: roadblock to differentiation.

PMID- 22956527
TI  - Mutation associations in RA-defiant APL.

PMID- 22956528
TI  - A Meg by any other name.

PMID- 22956529
TI  - GVHD protection? ThiNK iNKT cells.

PMID- 22956530
TI  - Clinical uses of the Bonfils Retromolar Intubation Fiberscope: a review.
AB  - The Bonfils Retromolar Intubation Fiberscope is a rigid, straight fiberoptic
      device with a 40-degree curved tip, which facilitates targeted intubation.
      Bonfils, using a retromolar approach to intubate tracheas of children with Pierre
      Robin syndrome, was first described in 1983. After an initial steep learning
      curve, the Bonfils becomes a useful device in the management of normal and
      difficult airways. The advantages lie in its performance as an optical intubating
      stylet, which allows visualization from the tip of the endotracheal tube during
      intubation. The slim profile makes it useful in patients with limited mouth
      opening and cervical spine movement. Unlike the flexible fiberoptic bronchoscope,
      its rigid structure improves maneuverability and allows insertion past soft
      tissue obstructions. Endoscopic orientation of the Bonfils is better than the
      flexible fiberoptic bronchoscope, and it is also portable, durable, and simple to
      set up. The main difficulty experienced by Bonfils users is common to all
      fiberoptic scopes, limited view due to blood, secretions, fogging, and tissue
      contact. Additionally, nasal intubation is not possible with the Bonfils, and
      direct trauma and barotrauma are possible. Although the intubation success rate
      is high, it is still very much operator dependent. Time to intubation is inferior
      to conventional laryngoscopy, and its expense may be an issue in some centers. In
      conclusion, the Bonfils is an effective tool for management of the difficult
      airway after initial training.

PMID- 22956531
TI  - The effective effect-site propofol concentration for induction and intubation
      with two pharmacokinetic models in morbidly obese patients using total body
      weight.
AB  - BACKGROUND: Most pharmacokinetic (PK) models used for propofol administration are
      based on studies in normal-weight patients. Extrapolation of these models for
      morbidly obese patients is controversial. Using 2 PK models and a target
      controlled infusion system, we determined the predicted propofol effect-site
      concentration (Ce) needed for induction of anesthesia in morbidly obese subjects
      using total body weight. METHODS: Sixty-six morbidly obese subjects from 18 to 50
      years of age were randomized to receive propofol to reach and maintain a
      predetermined propofol Ce, based on the PK models of either Marsh or Schnider.
      All patients were monitored with a Bispectral Index electroencephalographic
      monitor. Fentanyl 3 MUg/kg total body weight was administered before starting the
      propofol infusion. After loss of consciousness, vecuronium was administered to
      facilitate endotracheal intubation. Groups of 6 patients each received propofol
      at a different, predetermined target propofol Ce. An "effective Ce" (ECe) was
      defined as the propofol Ce that provided adequate hypnosis (Bispectral Index <60)
      during the complete induction period (45 seconds after reaching the predetermined
      target Ce until 5 minutes after tracheal intubation). Heart rate and arterial
      blood pressure were measured every 1 minute throughout the study period. Probit
      regression analysis was performed to calculate the effective propofol Ce values
      to induce hypnosis in 50% (ECe(50)) and 95% (ECe(95)) of patients with 95%
      confidence intervals (CIs). RESULTS: Patient characteristics were similar between
      models and across the propofol target concentration groups. The ECe(50) of
      propofol was 3.4 MUg/mL (95% CI: 2.9, 3.7 MUg/mL) with the Marsh model and 4.5
      MUg/mL (95% CI: 4.1, 4.8 MUg/mL) with the Schnider model (P < 0.001). The ECe(95)
      values were 4.2 MUg/mL (95% CI: 3.8, 6.2 MUg/mL) and 5.5 MUg/mL (95% CI: 5.0, 7.2
      MUg/mL) with Marsh and Schnider models, respectively. At the ECe(95), hemodynamic
      effects were similar with the 2 PK models. CONCLUSION: Different propofol target
      concentrations for each PK model must be used for induction when using total body
      weight in morbidly obese patients.

PMID- 22956532
TI  - A systematic review of resting left ventricular systolic and diastolic function
      and adaptation in elite weightlifters.
AB  - BACKGROUND: This review aims to establish what effect weightlifting has on the
      systolic and diastolic function of the left ventricular (LV). SOURCES OF DATA:
      PubMed; ISI Web of Knowledge; Cochrane Library and Ovid Medline were searched in
      February 2012 to find literature on the effect of weightlifting on the LV cardiac
      function. AREAS OF AGREEMENT: Stroke volume, posterior wall thickness and
      ventricular filling time and rate were seen to increase. A decrease in the
      resting heart rate was seen. AREAS OF CONTROVERSY: Blood pressure and LV
      morphological changes were equivocal. GROWING POINTS: Weightlifting causes
      recognizable functional change to the LV, some of these changes may confer
      benefits such as improvements in the systolic function. AREAS TIMELY FOR
      DEVELOPING RESEARCH: Discrepancies exist with regard to regional LV morphological
      change, as the evidence suggests the LV does not adapt in a homogenous manner.
      Attempts should be made to separate performance-enhancing drug users from those
      who compete drug free.

PMID- 22956533
TI  - Positive diversity-invasibility relationship in species-rich semi-natural
      grassland at the neighbourhood scale.
AB  - BACKGROUND AND AIMS: Attempts to answer the old question of whether high
      diversity causes high invasion resistance have resulted in an invasion paradox:
      while large-scale studies often find a positive relationship between diversity
      and invasibility, small-scale experimental studies often find a negative
      relationship. Many of the small-scale studies are conducted in artificial
      communities of even-aged plants. Species in natural communities, however, do not
      represent one simultaneous cohort and occur at various levels of spatial
      aggregation at different scales. This study used natural patterns of diversity to
      assess the relationship between diversity and invasibility within a uniformly
      managed, semi-natural community. METHODS: In species-rich grassland, one seed of
      each of ten species was added to each of 50 contiguous 16 cm(2) quadrats within
      seven plots (8 * 100 cm). The emergence of these species was recorded in seven
      control plots, and establishment success was measured in relation to the species
      diversity of the resident vegetation at two spatial scales, quadrat (64 cm(2))
      within plots (800 cm(2)) and between plots within the site (approx. 400 m(2))
      over 46 months. KEY RESULTS: Invader success was positively related to resident
      species diversity and richness over a range of 28-37 species per plot. This
      relationship emerged 7 months after seed addition and remained over time despite
      continuous mortality of invaders. CONCLUSIONS: Biotic resistance to plant
      invasion may play only a sub-ordinate role in species-rich, semi-natural
      grassland. As possible alternative explanations for the positive diversity
      invasibility relationship are not clear, it is recommended that future studies
      elaborate fine-scale environmental heterogeneity in resource supplies or
      potential resource flows from resident species to seedlings by means of soil
      biological networks established by arbuscular mycorrhizal fungi.

PMID- 22956534
TI  - Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity.
AB  - BACKGROUND: Chemotherapy-related amenorrhea is a frequent side effect observed in
      young breast cancer patients. Studies in mice revealed that chemotherapy-induced
      gonadal toxicity may result from vascular damage. We prospectively evaluated
      ovarian blood flow and function in young breast cancer patients following
      chemotherapy. METHODS: Young female patients with localized breast cancer
      undergoing adjuvant or neoadjuvant anthracycline- or taxane-based chemotherapy
      were evaluated using transvaginal ultrasound prior to initiation of and
      immediately after cessation of chemotherapy. Doppler-flow velocity indices of the
      ovarian vasculature-resistance index (RI), pulsatility index (PI)-and size
      measurements were visualized. Hormonal profiles, anti-Mullerian hormone (AMH)
      levels, and menopausal symptoms were assessed at the same time points. RESULTS:
      Twenty breast cancer patients were enrolled in the study. The median age was 34
      +/- 5.24 years. Ovarian blood flow was significantly reduced shortly following
      chemotherapy: RI decreased by 52.5% and PI decreased by 24.2%. The mean ovarian
      size declined by 19.08%. Patients who were treated with sequential chemotherapy
      experienced further reductions in ovarian blood flow and ovarian size after the
      second sequence. AMH levels dropped dramatically in all patients following
      treatment. Hormonal profiles after treatment depicted a postmenopausal profile
      for most patients, accompanied by related symptoms. CONCLUSIONS: Our results may
      imply a mechanism of chemotherapy-induced ovarian toxicity manifested by
      decreased ovarian blood flow accompanied by a reduction in ovarian size and
      diminished post-treatment AMH levels. Based upon our former preclinical studies,
      we assume that this may derive from an acute insult to the ovarian vasculature
      and may represent an initial event triggering a generalized phenomenon of end
      organ toxicity.

PMID- 22956535
TI  - The role of lung metastasis resection in improving outcome of colorectal cancer
      patients: results from a large retrospective study.
AB  - BACKGROUND: The role of surgery for lung metastases (LM) secondary to colorectal
      cancer (CRC) remains controversial. The bulk of evidence is derived from single
      surgical series, hampering any definitive conclusions. The aim of this study was
      to compare the outcomes of CRC patients with LM submitted to surgery with those
      who were not. PATIENTS AND METHODS: Data from 409 patients with LM as the first
      evidence of advanced disease were extracted from a database of 1,411 patients.
      Patients were divided into three groups: G1, comprised of 155 patients with
      pulmonary and extrapulmonary metastases; G2, comprised of 104 patients with LM
      only and no surgery; G3, comprised of 50 patients with LM only and submitted to
      surgery. RESULTS: No difference in response rates emerged between G1 and G2.
      Median progression-free survival (PFS) times were: 10.3 months, 10.5 months, and
      26.2 months for G1, G2, and G3, respectively. No difference in PFS times was
      observed between G1 and G2, whereas there was a statistically significant
      difference between G2 and G3. Median overall survival times were 24.2 months,
      31.5 months, and 72.4 months, respectively. Survival times were longer in
      resected patients: 17 survived >5 years and three survived >10 years. In patients
      with LM only and no surgery, four survived for 5 years and none survived >10
      years. CONCLUSIONS: Even though patients with resectable LM are more likely to be
      those with a better outcome, our study provides evidence suggesting an active
      role of surgery in improving survival outcomes in this patient subset.

PMID- 22956536
TI  - Body mass index and risk of primary liver cancer: a meta-analysis of prospective
      studies.
AB  - BACKGROUND: Questions remain about the dose-response relationship between body
      mass index (BMI) and primary liver cancer (PLC) risk, possible confounding by
      hepatitis virus infection, and differences by gender or geographic location. We
      performed a meta-analysis of prospective studies to explore these issues.
      METHODS: We searched PubMed and Embase for studies of BMI and risk of PLC through
      November 30, 2011. Summary relative risks with their corresponding 95% confidence
      intervals (CIs) were calculated using a random effects model. RESULTS: A total of
      21 prospective studies (including 17,624 PLC cases) were included in our
      analysis. The summary relative risk for a 5-unit increment in BMI (in kg/m(2))
      was 1.39 (95% CI: 1.25-1.55), with high heterogeneity. These positive results
      were robust when stratified by sex, geographic location, ascertainment of
      exposure and outcome, the number of cases, duration of follow-up, sample source,
      and cofounders. There was evidence of a nonlinear association between BMI and PLC
      risk, with the most pronounced increase in risk among persons with a BMI >32
      kg/m(2). Patients with hepatitis C virus or cirrhosis (but not patients with
      hepatitis B virus) with excess weight had a higher risk of PLC development than
      general populations with excess weight. CONCLUSION: Excess weight increases PLC
      risk. For people with HCV infection or cirrhosis, risk increases are greater than
      for general population.

PMID- 22956537
TI  - The doublecortin-related gene zyg-8 is a microtubule organizer in Caenorhabditis
      elegans neurons.
AB  - Doublecortin-domain containing (DCDC) genes play key roles in the normal and
      pathological development of the human brain cortex. The origin of the cellular
      specialisation and the functional redundancy of these microtubule (MT)-associated
      proteins (MAPs), especially those of Doublecortin (DCX) and Doublecortin-like
      kinase (DCLKs) genes, is still unclear. The DCX domain has the ability to control
      MT architecture and bundling. However, the physiological significance of such
      properties is not fully understood. To address these issues, we sought post
      mitotic roles for zyg-8, the sole representative of the DCX-DCLK subfamily of
      genes in C. elegans. Previously, zyg-8 has been shown to control anaphase-spindle
      positioning in one-cell stage embryos, but functions of the gene later in
      development have not been investigated. Here we show that wild-type zyg-8 is
      required beyond early embryonic divisions for proper development, spontaneous
      locomotion and touch sensitivity of adult worms. Consistently, we find zyg-8
      expression in the six touch receptor neurons (TRNs), as well as in a subset of
      other neuronal and non-neuronal cells. In TRNs and motoneurons, zyg-8 controls
      cell body shape/polarity and process outgrowth and morphology. Ultrastructural
      analysis of mutant animals reveals that zyg-8 promotes structural integrity,
      length and number of individual MTs, as well as their bundled organisation in
      TRNs, with no impact on MT architecture.

PMID- 22956538
TI  - Oscillation of APC/C activity during cell cycle arrest promotes centrosome
      amplification.
AB  - Centrosome duplication is licensed by the disengagement, or 'uncoupling', of
      centrioles during late mitosis. However, arrest of cells in G2 can trigger
      premature centriole disengagement. Here, we show that premature disengagement
      results from untimely activation of the anaphase-promoting complex (APC/C),
      leading to securin degradation and release of active separase. Although APC/C
      activation during G2 arrest is dependent on polo-like kinase 1 (Plk1)-mediated
      degradation of the APC/C inhibitor, early mitotic inhibitor 1 (Emi1), Plk1 also
      has a second APC/C-independent role in promoting disengagement. Importantly,
      APC/C and Plk1 activity also stimulates centriole disengagement in response to
      hydroxyurea or DNA damage-induced cell-cycle arrest and this leads to centrosome
      amplification. However, the reduplication of disengaged centrioles is dependent
      on cyclin-dependent kinase 2 (Cdk2) activity and Cdk2 activation coincides with a
      subsequent inactivation of the APC/C and re-accumulation of cyclin A. Although
      release from these arrests leads to mitotic entry, the presence of disengaged
      and/or amplified centrosomes results in the formation of abnormal mitotic
      spindles that lead to chromosome mis-segregation. Thus, oscillation of APC/C
      activity during cell cycle arrest promotes both centrosome amplification and
      genome instability.

PMID- 22956539
TI  - Intracellular chloride channel protein CLIC1 regulates macrophage function
      through modulation of phagosomal acidification.
AB  - Intracellular chloride channel protein 1 (CLIC1) is a 241 amino acid protein of
      the glutathione S transferase fold family with redox- and pH-dependent membrane
      association and chloride ion channel activity. Whilst CLIC proteins are
      evolutionarily conserved in Metazoa, indicating an important role, little is
      known about their biology. CLIC1 was first cloned on the basis of increased
      expression in activated macrophages. We therefore examined its subcellular
      localisation in murine peritoneal macrophages by immunofluorescence confocal
      microscopy. In resting cells, CLIC1 is observed in punctate cytoplasmic
      structures that do not colocalise with markers for endosomes or secretory
      vesicles. However, when these macrophages phagocytose serum-opsonised zymosan,
      CLIC1 translocates onto the phagosomal membrane. Macrophages from CLIC1(-/-) mice
      display a defect in phagosome acidification as determined by imaging live cells
      phagocytosing zymosan tagged with the pH-sensitive fluorophore Oregon Green. This
      altered phagosomal acidification was not accompanied by a detectable impairment
      in phagosomal-lysosomal fusion. However, consistent with a defect in
      acidification, CLIC1(-/-) macrophages also displayed impaired phagosomal
      proteolytic capacity and reduced reactive oxygen species production. Further,
      CLIC1(-/-) mice were protected from development of serum transfer induced K/BxN
      arthritis. These data all point to an important role for CLIC1 in regulating
      macrophage function through its ion channel activity and suggest it is a suitable
      target for the development of anti-inflammatory drugs.

PMID- 22956540
TI  - Inverse regulation of target genes at the brink of the BMP morphogen activity
      gradient.
AB  - BMP-dependent patterning in the Drosophila melanogaster wing imaginal disc serves
      as a paradigm to understand how morphogens specify cell fates. The observed
      profile of the transcriptional response to the graded signal of BMP relies upon
      two counter-active gradients of pMad and Brinker (Brk). This patterning model is
      inadequate to explain the expression of target genes, like vestigial and spalt,
      in lateral regions of the wing disc where BMP signals decline and Brk levels
      peak. Here, we show that in contrast to the reciprocal repressor gradient
      mechanism, where Brk represses BMP targets in medial regions, target expression
      in lateral regions is downregulated by BMP signalling and activated by Brk. Brk
      induces lateral expression indirectly, apparently through repression of a
      negative regulator. Our findings provide a model explaining how the expression of
      an established BMP target is differentially and inversely regulated along the
      anterior-posterior axis of the wing disc.

PMID- 22956541
TI  - Foxk1 promotes cell proliferation and represses myogenic differentiation by
      regulating Foxo4 and Mef2.
AB  - In response to severe injury, adult skeletal muscle exhibits a remarkable
      regenerative capacity due to a resident muscle stem/progenitor cell population.
      While a number of factors are expressed in the muscle progenitor cell (MPC)
      population, the molecular networks that govern this cell population remain an
      area of active investigation. In this study, utilizing knockdown techniques and
      overexpression of Foxk1 in the myogenic lineage, we observed dysregulation of
      Foxo and Mef2 downstream targets. Utilizing an array of technologies, we
      establish that Foxk1 represses the transcriptional activity of Foxo4 and Mef2 and
      physically interacts with Foxo4 and Mef2, thus promoting MPC proliferation and
      antagonizing the myogenic lineage differentiation program, respectively.
      Correspondingly, knockdown of Foxk1 in C2C12 myoblasts results in cell cycle
      arrest, and Foxk1 overexpression in C2C12CAR myoblasts retards muscle
      differentiation. Collectively, we have established that Foxk1 promotes MPC
      proliferation by repressing Foxo4 transcriptional activity and inhibits myogenic
      differentiation by repressing Mef2 activity. These studies enhance our
      understanding of the transcriptional networks that regulate the MPC population
      and muscle regeneration.

PMID- 22956542
TI  - Depletion of histone deacetylase 3 antagonizes PI3K-mediated overgrowth of
      Drosophila organs through the acetylation of histone H4 at lysine 16.
AB  - Core histone modifications play an important role in chromatin remodeling and
      transcriptional regulation. Histone acetylation is one of the best-studied gene
      modifications and has been shown to be involved in numerous important biological
      processes. Herein, we demonstrated that the depletion of histone deacetylase 3
      (Hdac3) in Drosophila melanogaster resulted in a reduction in body size. Further
      genetic studies showed that Hdac3 counteracted the organ overgrowth induced by
      overexpression of insulin receptor (InR), phosphoinositide 3-kinase (PI3K) or S6
      kinase (S6K), and the growth regulation by Hdac3 was mediated through the
      deacetylation of histone H4 at lysine 16 (H4K16). Consistently, the alterations
      of H4K16 acetylation (H4K16ac) induced by the overexpression or depletion of
      males-absent-on-the-first (MOF), a histone acetyltransferase that specifically
      targets H4K16, resulted in changes in body size. Furthermore, we found that
      H4K16ac was modulated by PI3K signaling cascades. The activation of the PI3K
      pathway caused a reduction in H4K16ac, whereas the inactivation of the PI3K
      pathway resulted in an increase in H4K16ac. The increase in H4K16ac by the
      depletion of Hdac3 counteracted the PI3K-induced tissue overgrowth and PI3K
      mediated alterations in the transcription profile. Overall, our studies indicated
      that Hdac3 served as an important regulator of the PI3K pathway and revealed a
      novel link between histone acetylation and growth control.

PMID- 22956543
TI  - Mechanism and function of Vav1 localisation in TCR signalling.
AB  - The antigen-specific binding of T cells to antigen presenting cells results in
      recruitment of signalling proteins to microclusters at the cell-cell interface
      known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange
      factor plays a critical role in T cell antigen receptor (TCR) signalling, leading
      to the activation of multiple pathways. We now show that it is recruited to
      microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we
      show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains
      of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein.
      Biophysical measurements show that Vav1 binds directly to these residues on SLP76
      and that efficient binding depends on the SH2 and SH3(B) domains of Vav1.
      Finally, we show that the same two domains are critical for the phosphorylation
      of Vav1 and its signalling function in TCR-induced calcium flux. We propose that
      Vav1 is recruited to the IS by binding to SLP76 and that this interaction is
      critical for the transduction of signals leading to calcium flux.

PMID- 22956544
TI  - Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts.
AB  - The chitin synthase that makes the primary septum during cell division in budding
      yeasts is an important therapeutic target with an unknown activation mechanism.
      We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1
      protein plays an essential but uncharacterised role at the cleavage site during
      cytokinesis. By combining a novel degron allele of INN1 with a point mutation in
      the C2-domain, we screened for mutations in other genes that suppress the
      resulting defect in cell division. In this way, we identified 22 dominant
      mutations of CHS2 (chitin synthase II) that map to two neighbouring sites in the
      catalytic domain. Chs2 in isolated cell membranes is normally nearly inactive
      (unless protease treatment is used to bypass inhibition); however, the dominant
      suppressor allele Chs2-V377I has enhanced activity in vitro. We show that Inn1
      associates with Chs2 in yeast cell extracts. It also interacts in a yeast two
      hybrid assay with the N-terminal 65% of Chs2, which contains the catalytic
      domain. In addition to compensating for mutations in the Inn1 C2-domain, the
      dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the
      Cyk3 protein. Our data support a model in which the C2-domain of Inn1 acts in
      conjunction with Cyk3 to regulate the catalytic domain of Chs2 during
      cytokinesis. These findings suggest novel approaches for developing future drugs
      against important fungal pathogens.

PMID- 22956545
TI  - The ATP permeability of pannexin 1 channels in a heterologous system and in
      mammalian taste cells is dispensable.
AB  - Afferent output in type II taste cells is mediated by ATP liberated through ion
      channels. It is widely accepted that pannexin 1 (Panx1) channels are responsible
      for ATP release in diverse cell types, including taste cells. While biophysical
      evidence implicates slow deactivation of ion channels following ATP release in
      taste cells, recombinant Panx1 activates and deactivates rapidly. This
      inconsistency could indicate that the cellular context specifies Panx1
      functioning. We cloned Panx1 from murine taste tissue, and heterologously
      expressed it in three different cell lines: HEK-293, CHO and neuroblastoma SK-N
      SH cells. In all three cell lines, Panx1 transfection yielded outwardly
      rectifying anion channels that exhibited fast gating and negligible permeability
      to anions exceeding 250 Da. Despite expression of Panx1, the host cells did not
      liberate ATP upon stimulation, making it unclear whether Panx1 is involved in
      taste-related ATP secretion. This issue was addressed using mice with genetic
      ablation of the Panx1 gene. The ATP-biosensor assay revealed that, in taste cells
      devoid of Panx1, ATP secretion was robust and apparently unchanged compared with
      the control. Our data suggest that Panx1 alone forms a channel that has
      insufficient permeability to ATP. Perhaps, a distinct subunit and/or a regulatory
      circuit that is absent in taste cells is required to enable a high ATP
      permeability mode of a native Panx1-based channel.

PMID- 22956546
TI  - An interaction between alpha7 nicotinic receptors and a G-protein pathway complex
      regulates neurite growth in neural cells.
AB  - The alpha7 acetylcholine nicotinic receptor (alpha7) is an important mediator of
      cholinergic transmission during brain development. Here we present an
      intracellular signaling mechanism for the alpha7 receptor. Proteomic analysis of
      immunoprecipitated alpha7 subunits reveals an interaction with a G protein
      pathway complex (GPC) comprising Galpha(i/o), GAP-43 and G protein regulated
      inducer of neurite outgrowth 1 (Gprin1) in differentiating cells. Morphological
      studies indicate that alpha7 receptors regulate neurite length and complexity via
      a Gprin1-dependent mechanism that directs the expression of alpha7 to the cell
      surface. alpha7-GPC interactions were confirmed in embryonic cortical neurons and
      were found to modulate the growth of axons. Taken together, these findings reveal
      a novel intracellular pathway of signaling for alpha7 within neurons, and suggest
      a role for its interactions with the GPC in brain development.

PMID- 22956547
TI  - RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent
      control of STAT1.
AB  - Crosstalk between keratinocytes and immune cells is crucial for the immunological
      barrier function of the skin, and aberrant crosstalk contributes to inflammatory
      skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1
      gene we found that RAC1 in keratinocytes plays an important role in modulating
      the interferon (IFN) response in skin. These RAC1 mutant mice showed increased
      sensitivity in an irritant contact dermatitis model, abnormal keratinocyte
      differentiation, and increased expression of immune response genes including the
      IFN signal transducer STAT1. Loss of RAC1 in keratinocytes decreased actin
      polymerization in vivo and in vitro and caused Arp2/3-dependent expression of
      STAT1, increased interferon sensitivity and upregulation of aberrant keratinocyte
      differentiation markers. This can be inhibited by the AP-1 inhibitor tanshinone
      IIA. Loss of RAC1 makes keratinocytes hypersensitive to inflammatory stimuli both
      in vitro and in vivo, suggesting a major role for RAC1 in regulating the
      crosstalk between the epidermis and the immune system.

PMID- 22956548
TI  - CXCL12 receptor preference, signal transduction, biological response and the
      expression of 5T4 oncofoetal glycoprotein.
AB  - CXCL12 is a pleiotropic chemokine capable of eliciting multiple signal
      transduction cascades and functions, via interaction with either CXCR4 or CXCR7.
      Factors that determine CXCL12 receptor preference, intracellular signalling route
      and biological response are poorly understood but are of central importance in
      the context of therapeutic intervention of the CXCL12 axis in multiple disease
      states. We have recently demonstrated that 5T4 oncofoetal glycoprotein
      facilitates functional CXCR4 expression leading to CXCL12 mediated chemotaxis in
      mouse embryonic cells. Using wild type (WT) and 5T4 knockout (5T4KO) murine
      embryonic fibroblasts (MEFs), we now show that CXCL12 binding to CXCR4 activates
      both the ERK and AKT pathways within minutes, but while these pathways are
      intact, they are non-functional in 5T4KO cells treated with CXCL12. Importantly,
      in the absence of 5T4 expression, CXCR7 is upregulated and becomes the
      predominant receptor for CXCL12, activating a distinct signal transduction
      pathway with slower kinetics involving transactivation of the epidermal growth
      factor receptor (EGFR), eliciting proliferation rather than chemotaxis. Thus the
      surface expression of 5T4 marks the use of the CXCR4 rather than the CXCR7
      receptor, with distinct consequences for CXCL12 exposure, relevant to the spread
      and growth of a tumour. Consistent with this hypothesis, we have identified human
      small cell lung carcinoma cells with similar 5T4/CXCR7 reciprocity that is
      predictive of biological response to CXCL12 and determined that 5T4 expression is
      required for functional chemotaxis in these cells.

PMID- 22956549
TI  - Serum complement factor H is associated with clinical and pathological activities
      of patients with lupus nephritis.
AB  - OBJECTIVE: The aim of this study was to investigate serum complement factor H
      (CFH) and its associations with clinical and pathological features in patients
      with LN. METHODS: Serum CFH was detected in 241 LN patients, 38 active and 11
      inactive patients with SLE without clinical evidence of renal involvement and 51
      normal controls. Serum CFH autoantibodies and CFH Tyr402His were screened in the
      241 LN patients. CFH deposition in kidneys was detected in some patients.
      RESULTS: Serum CFH levels in patients with LN at active phase were significantly
      lower than in 38 SLE patients or in normal controls. No serum anti-CFH
      autoantibodies were detected in patients with LN, and there was no significant
      difference in CFH Tyr402His distribution between patients with LN and normal
      controls. Glomerular expression of CFH was stronger than in normal controls.
      Serum CFH levels were mildly negatively associated with SLEDAI scores (r = 
      0.204, P = 0.001) and positively associated with serum C3 (r = 0.367, P < 0.001)
      and haemoglobulin levels (r = 0.193, P = 0.003). Patients with LN class III,
      subclass IV-S and those with thrombotic microangiopathy had the lowest serum CFH.
      CONCLUSION: Serum CFH levels were associated with disease activity of LN.

PMID- 22956550
TI  - Joint and tendon involvement in systemic lupus erythematosus: an ultrasound study
      of hands and wrists in 108 patients.
AB  - OBJECTIVE: To estimate the prevalence of, and identify factors associated with,
      hand and wrist US alterations in a large cohort of SLE patients. METHODS: One
      hundred and eight consecutive SLE patients were recruited and classified
      according to arthropathy type and the musculoskeletal item of the British Isles
      Lupus Assessment Group (BILAG) 2004 score. US examinations were performed on hand
      and wrist flexor tendons, wrist extensor tendons, second and third MCP and wrist
      joints bilaterally using a multi-planar scanning technique. RESULTS: US
      examination showed joint involvement in 42/108 (38.8%) subjects, tendon
      involvement in 44/108 (40.7%) and both in 22/108 (20.3%). Patients with rhupus
      syndrome (n = 8) carried a higher incidence of inflammatory changes (87%) and
      erosions (87%) compared with the six with Jaccoud's arthropathy (50% and 17%,
      respectively) and the 94 with non-deforming X-ray non-erosive arthropathy (37%
      and 21%, respectively). Power Doppler signal was prevalent in patients scoring A
      (n = 4) or B (n = 9) on the musculoskeletal item of the BILAG 2004, and was
      significantly more frequent at the joint (92%) and tendon (54%) level than in the
      26 patients scoring C (19%, P = 0.0007 and 15%, P = 0.016, respectively) and in
      the 69 scoring D (3%, P < 0.0001 and 3%, P < 0.0001). US changes in patients who
      scored C or D were more expressed at the tendon level (50% and 29%, respectively)
      than at the joint level (35% and 9%, respectively). CONCLUSION: The picture of
      musculoskeletal US in SLE depends on arthropathy subtype and disease activity. US
      examination could be a valid and reliable tool to monitor musculoskeletal
      features and therapeutic outcomes in SLE patients.

PMID- 22956551
TI  - A randomized, double-blind, placebo-controlled trial of low-dose oral
      prednisolone for treating painful hand osteoarthritis.
AB  - OBJECTIVE: Anti-inflammatory therapies are effective analgesics for OA. This
      study determined whether low-dose oral prednisolone (PNL) was an effective
      analgesic for hand OA. METHODS: This was a randomized, double-blind, placebo
      controlled trial of people with ACR criteria hand OA and baseline hand pain
      visual analogue scale (VAS) of >40/100 mm. Participants received 5 mg PNL or
      placebo daily for 4 weeks. Pain VAS, disease activity VAS, Australian/Canadian
      Hand Osteoarthritis Index and joint counts were performed at baseline, 4 and 12
      weeks. Primary outcome was the change in hand pain VAS at 4 weeks. Analysis of
      covariance was used for analysis, controlling for baseline values. To explore
      potential mechanism of action of PNL, non-contrast 0.2 Tesla MRI was performed on
      the most painful hand at baseline and 4 weeks. RESULTS: A total of 70
      participants were recruited (57 women, mean age 61 years, mean baseline pain VAS
      61.5 mm); 75% had more than one joint with definite MRI synovitis/effusion. At 4
      weeks the adjusted mean reduction in pain VAS was 19.9 mm (PNL group) and 16.8 mm
      (placebo group) (P = 0.54). There were no statistically significant differences
      in VAS, Australian/Canadian Hand Osteoarthritis Index or joint counts between
      placebo and PNL groups at 4 or 12 weeks. A total of 20 participants in each group
      achieved an Outcome Measures in Rheumatology-Osteoarthritis Research Society
      International response. Baseline synovitis/effusion did not predict response to
      treatment. CONCLUSION: This is the first randomized controlled trial of low-dose
      corticosteroid alone for painful hand OA, which demonstrated that short-term low
      dose oral PNL is not an effective analgesic treatment for hand OA. TRIAL
      REGISTRATION: International Standard Randomised Controlled Trial Number Register,
      www.isrctn.org, Trial number 99697616.

PMID- 22956552
TI  - Is it worth investigating coeliac disease in patients with rheumatic disorders?

PMID- 22956554
TI  - Mechanisms in endocrinology: Heart failure and thyroid dysfunction.
AB  - CONTEXT: Heart failure (HF) is a major cause of morbidity and mortality in Europe
      and in the United States. The aim of this review article was to assess the
      results of the prospective studies that evaluated the risk of HF in patients with
      overt and subclinical thyroid disease and discuss the mechanism of this
      dysfunction. EVIDENCE ACQUISITION: Reports published with the following search
      terms were searched:, thyroid, hypothyroidism, hyperthyroidism, subclinical
      hyperthyroidism, subclinical hypothyroidism, levothyroxine, triiodothyronine,
      antithyroid drugs, radioiodine, deiodinases, clinical symptoms, heart rate, HF,
      systolic function, diastolic function, systemic vascular resistance, endothelial
      function, amiodarone and atrial fibrillation. The investigation was restricted to
      reports published in English. EVIDENCE SYNTHESIS: The outcome of this analysis
      suggests that patients with untreated overt thyroid dysfunction are at increased
      risk of HF. Moreover, persistent subclinical thyroid dysfunction is associated
      with the development of HF in patients with serum TSH <0.1 or > 10 mU/l.
      CONCLUSIONS: The timely recognition and effective treatment of cardiac symptoms
      in patients with thyroid dysfunction is mandatory because the prognosis of HF may
      be improved with the appropriate treatment of thyroid dysfunction.

PMID- 22956555
TI  - Increasing use of radioiodine in young people with thyrotoxicosis in Great
      Britain.
AB  - OBJECTIVE: Radioiodine (RI) is an important therapeutic option in young patients
      with thyrotoxicosis. We wanted to determine whether RI is being used more
      frequently in this age group. DESIGN: National survey of Great Britain (England,
      Wales and Scotland). METHODS: Sixty-one medical physics departments were asked to
      provide the age and number of patients with thyrotoxicosis <21 years treated with
      RI (1990-2008). Information on the total number of RI treatments for
      thyrotoxicosis was also collected. RESULTS: Forty-three departments (70%), with
      representation from 21 of the 25 most populous areas of Great Britain, provided
      data on 69,258 treatments. The number of treatments recorded on patients <21
      years during this period was 560 (0.9%). The frequency of treatments in young
      people as a percentage of the total increased from 0.2% in 1990 to 1.5% in 2008
      (P<0.001). When the 18 centres submitting at least 17 years of data were
      analysed, a similar pattern was observed. The maximum number of young people
      treated was greatest in 2008 (62) with a fall in the youngest age at which RI was
      administered from 18 years (1990) to 11 years (2008). CONCLUSIONS: A rising
      proportion of patients with thyrotoxicosis receiving RI are in those <21 years.
      This is largely due to an increase in the number of young people treated with a
      reduction in the minimum age at RI administration. We suspect that European
      clinicians are becoming more comfortable with RI treatment in young people with
      thyrotoxicosis, although a changing incidence is a potential contributing factor.

PMID- 22956556
TI  - Seizures and type 1 diabetes mellitus: current state of knowledge.
AB  - In this review, we will try to analyze the possible coexistence between epilepsy
      or seizures and type 1 diabetes mellitus (T1DM), in order to establish if there
      is more than a casual association, and to investigate possible mechanisms
      underlying this link. Anti-glutamic acid decarboxylase antibodies (GAD-Abs) have
      been associated with T1DM and a great number of neurological diseases such as
      epilepsy. Epilepsy can be a feature of a large variety of autoimmune or
      inflammatory disorders. GAD-Abs can have a role at the basis of the possible link
      between epilepsy and T1DM, although their real pathogenetic mechanism in
      neurological diseases is still unknown. Metabolic conditions such as hypoglycemia
      and hyperglycemia, common problems in diabetic patients, may be also implicated,
      even if their underlying mechanism is minimally understood.

PMID- 22956557
TI  - Body composition and metabolic parameters are associated with variation in
      thyroid hormone levels among euthyroid young men.
AB  - OBJECTIVE: Thyroid disorders affect metabolism and body composition. Existing
      literature has been conflicting on whether this is also the case for thyroid
      hormone levels within the euthyroid range. Therefore, we have investigated the
      relationship between thyroid hormone concentrations and body composition together
      with metabolic parameters in a population of healthy euthyroid men. METHODS:
      Healthy male siblings (n=941, 25-45 years, median BMI 24.6) were recruited in a
      cross-sectional, population-based study; a history or treatment of thyroid
      disease and thyroid autoimmunity were exclusion criteria. Body composition and
      muscle cross-sectional area were assessed by dual-energy X-ray absorptiometry and
      peripheral quantitative computed tomography. Total (triiodothyronine (T(3);
      TT(3)) thyroxine and (T(4); TT(4))) and free thyroid hormones (FT(3) and FT(4)),
      TSH, and reverse T(3) (rT(3)) and thyroid-binding globulin (TBG) were determined
      using immunoassays. RESULTS: BMI was positively associated with (F)T(3)
      (P<0.0001). Whole body fat mass displayed positive associations with TT(3) and
      with (F)T(4) and TBG (P<=0.0006). Positive associations were further observed
      between leptin and (F)T(3), TT(4), and TBG (P<=0.0002). Inverse associations
      between lean mass and muscle cross-sectional area and (F)T(3), (F)T(4), and TBG
      were observed (P<=0.0003). Higher levels of (F)T(3) and TBG were associated with
      lower insulin sensitivity, assessed by homeostatic model assessment of insulin
      resistance (IR; P<=0.0001). No associations between TSH and body composition or
      metabolic parameters were seen. CONCLUSION: We show that a less favorable body
      composition (with higher fat and lower muscle mass and accompanying higher leptin
      concentrations) and IR are associated with higher thyroid hormone levels in
      healthy young men with well characterized euthyroidism.

PMID- 22956558
TI  - Single-step QuantiFERON screening of adult contacts: a prospective cohort study
      of tuberculosis risk.
AB  - BACKGROUND: The efffectiveness of tuberculosis (TB) contact screening programmes
      using interferon gamma release assays remains uncertain as prospective contact TB
      risk is not well characterised. OBJECTIVES: To quantify 2-year TB risk and
      evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT)
      in adult contacts. To compare TB risk between QFT tested subgroups stratified by
      exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB)
      and age (younger (16-35 years) versus older (>=36 years)). METHODS: Screening
      involved QFT testing in older contacts of SP and all younger contacts, 8-12 weeks
      after index notification. Chemoprevention (3RH) was offered to QFT positive (+)
      younger adults. TB risk was determined in a prospective cohort study. RESULTS: 43
      TB events occurred in 1769 adult contacts observed for median 717 days (2-year
      rate (95% CI)=2.5% (1.7 to 3.2)). Index-contact strain matching was demonstrable
      for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB.
      215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated
      QFT+ adults developed TB (2-year rate (95% CI)=13.4% (7.7 to 21.1)). The model
      required 35 contacts screened with QFT to identify one contact developing TB at 2
      years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio
      (RR)=0.98, p=0.962). For QFT+ older contacts, the disease rate was lower (8.9%
      (3.3 to 19.1)) and similar to the overall group rate (RR=1.4, p=0.503).
      CONCLUSIONS: QFT based single-step contact screening is effective in young
      adults.

PMID- 22956559
TI  - Setting objectives for the NHS Commissioning Board.

PMID- 22956562
TI  - French diagnostic reference levels in diagnostic radiology, computed tomography
      and nuclear medicine: 2004-2008 review.
AB  - After 5 y of collecting data on diagnostic reference levels (DRLs), the Nuclear
      Safety and Radiation Protection French Institute (IRSN) presents the analyses of
      this data. The analyses of the collected data for radiology, computed tomography
      (CT) and nuclear medicine allow IRSN to estimate the level of regulatory
      application by health professionals and the representativeness of current DRL in
      terms of relevant examinations, dosimetric quantities, numerical values and
      patient morphologies. Since 2004, the involvement of professionals has highly
      increased, especially in nuclear medicine, followed by CT and then by radiology.
      Analyses show some discordance between regulatory examinations and clinical
      practice. Some of the dosimetric quantities used for the DRL setting are
      insufficient or not relevant enough, and some numerical values should also be
      reviewed. On the basis of these findings, IRSN formulates recommendations to
      update regulatory DRL with current and relevant examination lists, dosimetric
      quantities and numerical values.

PMID- 22956561
TI  - Bayer challenges India's first compulsory licence for generic version of cancer
      drug.

PMID- 22956563
TI  - Survey on risk perception of radiation following an incident involving a stuck
      60Co source in Henan province, China.
AB  - In July 2009, an incident involving a stuck Co-60 source led hundreds of
      thousands of people to escape Qi County, Henan Province, China, although no
      medical or environmental consequences were related to the incident. To
      investigate knowledge about radiation, public risk-perception of radiation, and
      evaluation of the official response, a survey was conducted in Qi and Hui County
      (control). Face-to-face questionnaire interviews were conducted among three
      groups with different educational backgrounds. In total, 1340 valid
      questionnaires were collected from people interviewed. Knowledge about radiation
      was low in all groups in both counties, although knowledge in Qi County was
      higher than that in Hui County (control). More than 40% respondents supported
      construction of nuclear power plants (NPPs) in China, while only a few supported
      constructing NPPs in their vicinity. The main reasons for the mass escape
      following the incident were assumed to be lack of knowledge about radiation,
      misinformation, the government's failure to disclose information in time and
      imitation of group behaviour. Over 60% in Group I and II trusted the local
      government. About 64% disapproved the response of the Qi County government. After
      the incident, the population in Qi County still knows little about radiation.
      Although people trust the government, they are dissatisfied with the response of
      the local government regarding the incident.

PMID- 22956564
TI  - Is Australian psychiatry getting SHIP shape?

PMID- 22956565
TI  - People living with psychosis: the good news and the bad news.

PMID- 22956566
TI  - The costs of early intervention in psychosis: restoring the balance.

PMID- 22956567
TI  - Burning the straw men: Intellectual integrity in the early intervention debate.

PMID- 22956568
TI  - Cardiometabolic risk factors in people with psychotic disorders: the second
      Australian survey of psychosis: going back to the foundations.

PMID- 22956569
TI  - Selective bias in early intervention for psychosis.

PMID- 22956570
TI  - Selective bias in criticism of early intervention.

PMID- 22956571
TI  - The TIPS study and bias: replies to Dr Amos.

PMID- 22956572
TI  - Atypical antipsychotic medication: a nightmarish problem!

PMID- 22956573
TI  - Continuation of clozapine following mild myocarditis.

PMID- 22956575
TI  - TAVI in heart failure, how much risk is acceptable?

PMID- 22956574
TI  - Chronic kidney disease and cardiac remodelling in patients with mild heart
      failure: results from the REsynchronization reVErses Remodeling in Systolic Left
      vEntricular Dysfunction (REVERSE) study.
AB  - AIMS: Chronic kidney disease (CKD) is a risk factor for left ventricular
      hypertrophy (LVH) and heart failure. We evaluated the effect of CKD on left
      ventricular (LV) remodelling among patients with mild heart failure. METHODS AND
      RESULTS: REVERSE was a randomized, controlled trial evaluating cardiac
      resynchronization therapy (CRT) in patients with New York Heart Association
      (NYHA) class I/II heart failure. CKD was defined as an estimated glomerular
      filtration rate (eGFR) <60 mL/min/1.73 m(2). We compared changes in LV function
      and size over the course of 12 months by CKD status using linear mixed models
      adjusted for demographics, co-morbidities, medications, cardiomyopathy aetiology,
      and CRT status. Finally, we evaluated the effect of CKD on cardiac remodelling
      among patients randomized to CRT on or off. CKD was associated with worsening LV
      function and dilation compared with the non-CKD group {adjusted, 12-month beta
      coefficients for the CKD group compared with the non-CKD referent group: LV
      ejection fraction (%) [-1.80, 95% confidence interval (CI) -3.36 to -0.24], LV
      end-systolic volume (mL) (14.16, 95% CI 3.96-24.36), LV end-diastolic volume (mL)
      (14.88, 95% CI 2.88-26.76), LV end-systolic diameter (cm) (0.36, 95% CI 0.12
      0.48), LV end-diastolic diameter (cm) (0.24, 95% CI 0.012-0.36), mitral
      regurgitation (%) (3.12, 95% CI 0.48-5.76), and LV shape (0.036, 95% CI 0.012
      0.060)}. In participants assigned to CRT, those without CKD had significantly
      greater improvements in LV structural parameters compared with the CKD group.
      CONCLUSIONS: In comparison with participants with normal kidney function, CKD is
      an independent risk factor for ventricular dysfunction and dilation. CRT improves
      LV function and structure to a lesser extent in patients with CKD than in those
      with normal kidney function.

PMID- 22956576
TI  - Regulation of B cell linker protein transcription by PU.1 and Spi-B in murine B
      cell acute lymphoblastic leukemia.
AB  - B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with
      mutations or chromosomal translocations of genes encoding transcription factors.
      Conditional deletion of genes encoding the E26-transformation-specific
      transcription factors, PU.1 and Spi-B, in B cells (DeltaPB mice) leads to B-ALL
      in mice at 100% incidence rate and with a median survival of 21 wk. We
      hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes
      encoding tumor suppressors in the B cell lineage. Characterization of aging
      DeltaPB mice showed that leukemia cells expressing IL-7R were found in enlarged
      thymuses. IL-7R-expressing B-ALL cells grew in culture in response to IL-7 and
      could be maintained as cell lines. Cultured DeltaPB cells expressed reduced
      levels of B cell linker protein (BLNK), a known tumor suppressor gene, compared
      with controls. The Blnk promoter contained a predicted PU.1 and/or Spi-B binding
      site that was required for promoter activity and occupied by PU.1 and/or Spi-B as
      determined by chromatin immunoprecipitation. Restoration of BLNK expression in
      cultured DeltaPB cells opposed IL-7-dependent proliferation and induced early
      apoptosis. We conclude that the tumor suppressor BLNK is a target of
      transcriptional activation by PU.1 and Spi-B in the B cell lineage.

PMID- 22956577
TI  - Crosstalk between human IgG isotypes and murine effector cells.
AB  - Development of human therapeutic Abs has led to reduced immunogenicity and
      optimal interactions with the human immune system in patients. Humanization had
      as a consequence that efficacy studies performed in mouse models, which represent
      a crucial step in preclinical development, are more difficult to interpret
      because of gaps in our knowledge of the activation of murine effector cells by
      human IgG (hIgG) remain. We therefore developed full sets of human and mouse
      isotype variants of human Abs targeting epidermal growth factor receptor and CD20
      to explore the crosstalk with mouse FcgammaRs (mFcgammaRs) and murine effector
      cells. Analysis of mFcgammaR binding demonstrated that hIgG1 and hIgG3 bound to
      all four mFcgammaRs, with hIgG3 having the highest affinity. hIgG1 nevertheless
      was more potent than hIgG3 in inducing Ab-dependent cellular cytotoxicity (ADCC)
      and Ab-dependent cellular phagocytosis with mouse NK cells, mouse
      polymorphonuclear leukocytes, and mouse macrophages. hIgG4 bound to all
      mFcgammaRs except mFcgammaRIV and showed comparable interactions with murine
      effector cells to hIgG3. hIgG4 is thus active in the murine immune system, in
      contrast with its inert phenotype in the human system. hIgG2 bound to
      mFcgammaRIIb and mFcgammaRIII, and induced potent ADCC with mouse NK cells and
      mouse polymorphonuclear leukocytes. hIgG2 induced weak ADCC and, remarkably, was
      unable to induce Ab-dependent cellular phagocytosis with mouse macrophages.
      Finally, the isotypes were studied in s.c. and i.v. tumor xenograft models, which
      confirmed hIgG1 to be the most potent human isotype in mouse models. These data
      enhance our understanding of the crosstalk between hIgGs and murine effector
      cells, permitting a better interpretation of human Ab efficacy studies in mouse
      models.

PMID- 22956578
TI  - Spleen tyrosine kinase is important in the production of proinflammatory
      cytokines and cell proliferation in human mesangial cells following stimulation
      with IgA1 isolated from IgA nephropathy patients.
AB  - IgA immune complexes are capable of inducing human mesangial cell (HMC)
      activation, resulting in release of proinflammatory and profibrogenic mediators.
      The subsequent inflammation, cellular proliferation, and synthesis of
      extracellular matrix lead to the progression of IgA nephropathy (IgAN). Spleen
      tyrosine kinase (SYK) is an intracellular protein tyrosine kinase involved in
      cell signaling downstream of immunoreceptors. In this study, we determined
      whether SYK is involved in the downstream signaling of IgA1 stimulation in HMC,
      leading to production of proinflammatory cytokines/chemokines and cell
      proliferation. Incubation of HMC with IgA1 purified from IgAN patients
      significantly increased the synthesis of MCP-1 in a dose-dependent manner. There
      was also significantly increased production of IL-6, IL-8, IFN-gamma-inducible
      protein-10, RANTES, and platelet-derived growth factor-BB. Stimulation of HMC
      with heat-aggregated IgA1 purified from IgAN patients induced significantly
      increased HMC proliferation. Both pharmacological inhibition of SYK and knockdown
      of SYK by small interfering RNA significantly reduced the synthesis of these
      mediators and inhibited HMC proliferation. Moreover, positive immunostaining for
      total and phospho-SYK in glomeruli of kidney biopsies from IgAN patients strongly
      suggests the involvement of SYK in the pathogenesis of IgAN. To our knowledge, we
      demonstrate, for the first time, the involvement of SYK in the downstream
      signaling of IgA1 stimulation in HMC and in the pathogenesis of IgAN. Hence, SYK
      represents a potential therapeutic target for IgAN.

PMID- 22956579
TI  - Protective role for TLR4 signaling in atherosclerosis progression as revealed by
      infection with a common oral pathogen.
AB  - Clinical and epidemiological studies have implicated chronic infections in the
      development of atherosclerosis. It has been proposed that common mechanisms of
      signaling via TLRs link stimulation by multiple pathogens to atherosclerosis.
      However, how pathogen-specific stimulation of TLR4 contributes to atherosclerosis
      progression remains poorly understood. In this study, atherosclerosis-prone
      apolipoprotein-E null (ApoE(-/-)) and TLR4-deficient (ApoE(-/-)TLR4(-/-)) mice
      were orally infected with the periodontal pathogen Porphyromonas gingivalis.
      ApoE(-/-)TLR4(-/-) mice were markedly more susceptible to atherosclerosis after
      oral infection with P. gingivalis. Using live animal imaging, we demonstrate that
      enhanced lesion progression occurs progressively and was increasingly evident
      with advancing age. Immunohistochemical analysis of lesions from ApoE(-/-)TLR4(-/
      ) mice revealed an increased inflammatory cell infiltrate composed primarily of
      macrophages and IL-17 effector T cells (Th17), a subset linked with chronic
      inflammation. Furthermore, enhanced atherosclerosis in TLR4-deficient mice was
      associated with impaired development of Th1 immunity and regulatory T cell
      infiltration. In vitro studies suggest that the mechanism of TLR4-mediated
      protective immunity may be orchestrated by dendritic cell IL-12 and IL-10, which
      are prototypic Th1 and regulatory T cell polarizing cytokines. We demonstrate an
      atheroprotective role for TLR4 in response to infection with the oral pathogen P.
      gingivalis. Our results point to a role for pathogen-specific TLR signaling in
      chronic inflammation and atherosclerosis.

PMID- 22956580
TI  - Homeostatic division is not necessary for antigen-specific CD4+ memory T cell
      persistence.
AB  - CD4(+) memory T cells are generated in response to infection or vaccination,
      provide protection to the host against reinfection, and persist through a
      combination of enhanced survival and slow homeostatic turnover. We used timed
      deletion of the TCR-signaling adaptor molecule Src homology 2 domain-containing
      phosphoprotein of 76 kDa (SLP-76) with MHC:peptide tetramers to study the
      requirements for tonic TCR signals in the maintenance of polyclonal Ag-specific
      CD4(+) memory T cells. SLP-76-deficient I-A(b):gp61 cells are unable to rapidly
      generate effector cytokines or proliferate in response to secondary infection. In
      mice infected with lymphocytic choriomeningitis virus (LCMV) or Listeria
      monocytogenes expressing the LCMV gp61-80 peptide, SLP-76-deficient I
      A(b):gp61(+) cells exhibit reduced division, similar to that seen in in vitro
      generated CD44(hi) and endogenous CD4(+)CD44(hi) cells. Competitive bone marrow
      chimera experiments demonstrated that the decrease in homeostatic turnover in the
      absence of SLP-76 is a cell-intrinsic process. Surprisingly, despite the
      reduction in turnover, I-A(b):gp61(+) Ag-specific memory cells persist in normal
      numbers for >30 wk after LCMV infection in the absence of SLP-76. These data
      suggest the independent maintenance of a population of Ag-specific CD4(+) memory
      T cells in the absence of SLP-76 and normal levels of homeostatic division.

PMID- 22956581
TI  - Murine immunodeficiency virus-induced peripheral neuropathy and the associated
      cytokine responses.
AB  - Distal symmetrical polyneuropathy is the most common form of HIV infection
      associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6)
      mice infected with LP-BM5, a murine retroviral isolate, develop a severe
      immunodeficiency syndrome similar to that in humans infected with HIV-1, hence
      the term murine AIDS. We investigated the induction of peripheral neuropathy
      after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans,
      exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and
      pathological (transient loss of intraepidermal nerve fibers) signs of peripheral
      neuropathy. The levels of viral gag RNA were significantly increased in all
      tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and
      lumbar spinal cord, postinfection (p.i.). Correlated with the development of
      peripheral neuropathy, the tissue levels of several cytokines, including IFN
      gamma, IL-1beta, IL-6, and IL-12, were significantly elevated p.i. These
      increases had cytokine-specific and tissue-specific profiles and kinetics.
      Further, treatment with the antiretroviral agent zidovudine either significantly
      reduced or completely reversed the aforementioned behavioral, pathologic, and
      cytokine changes p.i. These data suggest that LP-BM5 infection is a potential
      mouse model of HIV-associated distal symmetrical polyneuropathy that can be used
      for investigating the roles of various cytokines in infection-induced neuropathic
      pain. Further investigation of this model could give a better understanding of,
      and lead to more effective treatments for, HIV infection-associated painful
      peripheral neuropathy.

PMID- 22956582
TI  - A2B adenosine receptor expression by myeloid cells is proinflammatory in murine
      allergic-airway inflammation.
AB  - Asthma is a chronic condition with high morbidity and healthcare costs, and
      cockroach allergens are an established cause of urban pediatric asthma. A better
      understanding of cell types involved in promoting lung inflammation could provide
      new targets for the treatment of chronic pulmonary disease. Because of its role
      in regulating myeloid cell-dependent inflammatory processes, we examined A(2B) R
      expression by myeloid cells in a cockroach allergen model of murine asthma-like
      pulmonary inflammation. Both systemic and myeloid tissue-specific A(2B) R
      deletion significantly decreased pulmonary inflammatory cell recruitment, airway
      mucin production, and proinflammatory cytokine secretion after final allergen
      challenge in sensitized mice. A(2B) R deficiency resulted in a dramatic reduction
      on Th2-type airways responses with decreased pulmonary eosinophilia without
      augmenting neutrophilia, and decreased lung IL-4, IL-5, and IL-13 production.
      Chemokine analysis demonstrated that eotaxin 1 and 2 secretion in response to
      repeated allergen challenge is myeloid cell A(2B) R dependent. In contrast, there
      were no differences in the levels of the CXC chemokines keratinocyte-derived
      chemokine and MIP-2 in the myeloid cell A(2B) R-deficient mice, strengthening
      A(2B) R involvement in the development of Th2-type airways inflammation.
      Proinflammatory TNF-alpha, IFN-gamma, and IL-17 secretion were also reduced in
      systemic and myeloid tissue-specific A(2B) R deletion mouse lines. Our results
      demonstrate Th2-type predominance for A(2B) R expression by myeloid cells as a
      mechanism of development of asthma-like pulmonary inflammation.

PMID- 22956583
TI  - Ganglioside inhibition of CD8+ T cell cytotoxicity: interference with lytic
      granule trafficking and exocytosis.
AB  - Granule exocytosis-mediated cytotoxicity by CD8(+) CTL plays a crucial role in
      adaptive immunity to tumors and to intracellular pathogens. This T cell effector
      function has been shown to be defective in various murine tumor models and in
      human cancer. However, factors and their mechanisms that cause inhibition of
      CD8(+) T cell lytic function in tumor-bearing hosts remain to be fully defined.
      We postulate that gangliosides, highly expressed on tumor cell membranes,
      actively shed into the tumor microenvironment, and having well-established
      immunosuppressive properties, may be such a factor. We exposed primary mouse
      CD8(+) CTL to gangliosides derived from three sources (tumors and normal brain).
      This significantly inhibited cytotoxicity-mediated by granule exocytosis, that
      is, cytotoxicity of alloantigen-specific and polyclonal CD8(+) CTL in vitro.
      These molecules did not interfere with the interaction of CD8(+) T cells with
      their cognate targets. Rather, they inhibited lytic granule release in response
      both to TCR engagement and to stimuli that induce granule release in a
      nonpolarized manner. At the subcellular level, confocal microscopic imaging
      identified inhibition of polarization of lytic granules to the immunological
      synapse upon target cell recognition. Thus, tumor-shed gangliosides suppress
      lytic activity of CD8(+) T cells by a novel mechanism, that is, inhibition of
      trafficking of lytic granules in response to TCR engagement, as well as by
      interfering with the process of granule exocytosis in CD8(+) T cells.

PMID- 22956584
TI  - The Yersinia pseudotuberculosis outer membrane protein Ail recruits the human
      complement regulatory protein factor H.
AB  - Previous investigations characterizing the mechanism(s) of complement resistance
      in Yersinia pseudotuberculosis showed that the outer membrane protein Ail can
      functionally recruit the regulator of the classical and lectin pathways of
      complement, C4b-binding protein. In this study, we extend these observations and
      show that Ail can also recruit the regulator of the alternative pathway (AP),
      factor H (fH). Binding to fH was dependent on Ail expression and observed in the
      context of full-length LPS. Inactivation of ail resulted in loss of fH binding.
      Ail expression conferred resistance to AP-mediated killing. Bound fH was
      functional as a cofactor for factor I-mediated cleavage and inactivation of C3b.
      Ail alone is sufficient to mediate fH binding and resistance to AP-mediated
      killing, because Ail expression in a laboratory Escherichia coli strain conferred
      both of these phenotypes. Binding was specific and inhibited by increasing
      heparin and NaCl concentrations. Using a panel of fH recombinant fragments, we
      observed that both short consensus repeats 5-7 and 19-20 regions are responsible
      for mediating the interaction with Ail. Collectively, these results suggest that
      fH recruitment is an additional mechanism of complement resistance of Ail.
      Recruitment of both fH and C4BP by Ail may confer Y. pseudotuberculosis with the
      ability to resist all pathways of complement activation.

PMID- 22956585
TI  - Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in
      prostate cancer patients.
AB  - CTLA-4 is a surface receptor on activated T cells that delivers an inhibitory
      signal, serving as an immune checkpoint. Treatment with anti-CTLA-4 Abs can
      induce clinical responses to different malignancies, but the nature of the
      induced Ag-specific recognition is largely unknown. Using microarrays spotted
      with >8000 human proteins, we assessed the diversity of Ab responses modulated by
      treatment with CTLA-4 blockade and GM-CSF. We find that advanced prostate cancer
      patients who clinically respond to treatment also develop enhanced Ab responses
      to a higher number of Ags than nonresponders. These induced Ab responses targeted
      Ags to which preexisting Abs are more likely to be present in the clinical
      responders compared with nonresponders. The majority of Ab responses are patient
      specific, but immune responses against Ags shared among clinical responders are
      also detected. One of these shared Ags is PAK6, which is expressed in prostate
      cancer and to which CD4(+) T cell responses were also induced. Moreover,
      immunization with PAK6 can be both immunogenic and protective in mouse tumor
      models. These results demonstrate that immune checkpoint blockade modulates Ag
      specific responses to both individualized and shared Ags, some of which can
      mediate anti-tumor responses.

PMID- 22956586
TI  - Targeting a novel onco-glycoprotein antigen at tumoral pancreatic cell surface by
      mAb16D10 induces cell death.
AB  - The mAb16D10 was raised against a pathological onco-glycoform of bile salt
      dependent lipase isolated from the pancreatic juice of a patient suffering from a
      pancreatic adenocarcinoma. We previously showed that mAb16D10 specifically
      discriminates human pancreatic tumor tissues from other cancer and nontumor
      tissues. In this study, we report that mAb16D10 inhibited the proliferation of
      only human pancreatic tumor cells expressing 16D10 plasma membrane Ag.
      Interaction of mAb16D10 with its cognate surface Ag on pancreatic cells promoted
      cell death by activation of the p53- and caspase-dependent apoptotic pathway, and
      silencing of p53 decreased cell death. The decreased proliferation was also
      partly due to cell cycle arrest in G1/S phase, mAb16D10 triggering of glycogen
      synthase kinase-3beta (GSK-3beta) activation, degradation of beta-catenin, and
      decreased expression of cyclin D1. GSK-3beta positively affected p53 expression
      in pancreatic tumor cells after mAb16D10 binding. Inhibition of GSK-3beta
      activity reversed the effects induced by mAb16D10 in SOJ-6 cells, supporting the
      pivotal role of GSK-3beta signaling in the mechanisms of action induced by
      mAb16D10. Also, mAb16D10 cell treatment led to membrane overexpression of E
      cadherin. Both E-cadherin and tumor Ag were localized in membrane lipid
      cholesterol-rich microdomains and are thought to belong to signaling platforms
      involved in the induction of cell cycle arrest and cell death. Overall, this
      study reveals that mAb16D10 holds great potential to prevent pancreatic tumor
      proliferation by apoptotic cell death, thus promising therapeutic prospects for
      treatment of pancreatic adenocarcinoma, a highly lethal disease.

PMID- 22956587
TI  - T cell costimulation by TNFR superfamily (TNFRSF)4 and TNFRSF25 in the context of
      vaccination.
AB  - TNFR superfamily (TNFRSF)4 (OX40, CD134) and TNFRSF25 are costimulatory receptors
      that influence CD4(+) and CD8(+) T cell responses to cognate Ag. Independently,
      these receptors have been described to stimulate overlapping functions, including
      enhanced proliferation and activation for both regulatory T cells
      (CD4(+)Foxp3(+); Tregs) and conventional T cells (CD4(+)Foxp3(-) or CD8(+)Foxp3(
      ); Tconvs). To determine the relative functionality of TNFRSF4 and TNFRSF25 in T
      cell immunity, the activity of TNFRSF4 and TNFRS25 agonistic Abs was compared in
      the context of both traditional protein/adjuvant (OVA/aluminum hydroxide) and
      CD8(+)-specific heat shock protein-based (gp96-Ig) vaccine approaches. These
      studies demonstrate that both TNFRSF4 and TNFRSF25 independently and additively
      costimulate vaccine-induced CD8(+) T cell proliferation following both primary
      and secondary Ag challenge. In contrast, the activities of TNFRSF4 and TNFRSF25
      were observed to be divergent in the costimulation of CD4(+) T cell immunity.
      TNFRSF4 agonists were potent costimulators of OVA/aluminum hydroxide-induced
      CD4(+) Tconv proliferation, but they only weakly costimulated Treg proliferation
      and IgG2a production, whereas TNFRSF25 agonists were strong costimulators of Treg
      proliferation, producers of IgG1, IgG2a, and IgG2b, and weak costimulators of
      CD4(+) Tconv proliferation. Interestingly, Ag-specific cellular and humoral
      responses were uncoupled upon secondary immunization, which was dramatically
      affected by the presence of TNFRSF4 or TNFRSF25 costimulation. These studies
      highlight the overlapping but nonredundant activities of TNFRSF4 and TNFRSF25 in
      T cell immunity, which may guide the application of receptor agonistic agents as
      vaccine adjuvants for infectious disease and tumor immunity.

PMID- 22956588
TI  - Technological advances in the treatment of trauma: a review of promising
      practices.
AB  - Given the availability of empirically supported practices for addressing
      posttraumatic stress disorder and other forms of trauma-related distress, the
      development and implementation of new technology to deliver these treatments is
      exciting. Technological innovations in this literature aim to expand availability
      of empirically based intervention, increase treatment adherence and
      acceptability, and overcome barriers commonly encountered with conventional
      trauma-focused treatment. Much of the current research on these technological
      developments consists of brief reviews and case studies of the separate therapy
      modalities. Although this work serves to document the appeal and utility of these
      innovations, it does not provide comprehensive information about the host of
      options available. To that end, the three general categories of technological
      advances in trauma therapy (i.e., videoconferencing, e-Health, virtual reality)
      are reviewed here, including information regarding their empirical support and
      suggestions for future research and clinical practice.

PMID- 22956589
TI  - Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a
      prospective cohort study.
AB  - OBJECTIVE: To test whether elevated concentration of rheumatoid factor is
      associated with long term development of rheumatoid arthritis. DESIGN: A
      prospective cohort study, the Copenhagen City Heart Study. Blood was drawn in
      1981-83, and participants were followed until 10 August 2010. SETTING: Copenhagen
      general population. PARTICIPANTS: 9712 white Danish individuals from the general
      population aged 20-100 years without rheumatoid arthritis at study entry. MAIN
      OUTCOME MEASURES: Rheumatoid arthritis according to baseline plasma IgM
      rheumatoid factor level categories of 25-50, 50.1-100, and >100, versus <25
      IU/mL. RESULTS: Rheumatoid factor levels were similar from age 20 to 100 years.
      During 187,659 person years, 183 individuals developed rheumatoid arthritis. In
      healthy individuals, a doubling in levels of rheumatoid factor was associated
      with a 3.3-fold (95% confidence interval 2.7 to 4.0) increased risk of developing
      rheumatoid arthritis, with a similar trend for most other autoimmune rheumatic
      diseases. The cumulative incidence of rheumatoid arthritis increased with
      increasing rheumatoid factor category (P(trend)<0.0001). Multivariable adjusted
      hazard ratios for rheumatoid arthritis were 3.6 (95% confidence interval 1.7 to
      7.3) for rheumatoid factor levels of 25-50 IU/mL, 6.0 (3.4 to 10) for 50.1-100
      IU/mL, and 26 (15 to 46) for >100 IU/mL, compared with <25 IU/mL
      (P(trend)<0.0001). The highest absolute 10 year risk of rheumatoid arthritis of
      32% was observed in 50-69 years old women who smoked with rheumatoid factor
      levels >100 IU/mL. CONCLUSION: Individuals in the general population with
      elevated rheumatoid factor have up to 26-fold greater long term risk of
      rheumatoid arthritis, and up to 32% 10 year absolute risk of rheumatoid
      arthritis. These novel findings may lead to revision of guidelines for early
      referral to a rheumatologist and early arthritis clinics based on rheumatoid
      factor testing.

PMID- 22956591
TI  - Rheumatoid factor positivity in the general population.

PMID- 22956592
TI  - Spatial relationship between high-dominant-frequency sites and the linear
      ablation line in persistent atrial fibrillation: its impact on complex
      fractionated electrograms.
AB  - AIMS: Complex fractionated electrograms (CFEs) and high-dominant-frequency (DF)
      sites theoretically represent abnormal substrates and targets for atrial
      fibrillation (AF) ablation. The relationship between the high-DF sites in the
      left atrium (LA) and commonly used linear ablation line to the distribution of
      the CFEs in patients with persistent AF is unknown. METHODS AND RESULTS: This
      study enrolled 62 persistent AF patients who underwent construction of LA CFE and
      DF maps (>350 points/map). Circumferential pulmonary vein isolation and linear
      ablation including that at the septum, roof, mitral-annulus, and ridge of the
      appendage were performed. Multipolar catheter mapping identified sites with high
      DFs (>= 8 Hz) in all patients (9.8 +/- 4.6/patient). In 47 patients in whom AF
      persisted despite ablation, there was a significant reduction in the continuous
      CFE (<50 ms) burden after the linear ablation (62 vs.11%; P < 0.0001), with a
      decrease in both the DF within the coronary sinus (6.9 +/- 0.9 vs. 5.9 +/- 0.8
      Hz; P < 0.0001) and CFE surface area (42.8 +/- 18.8 vs. 12.6 +/- 10.5 cm(2); P <
      0.0001). Comparing the high-DF sites with the ablated lesions, 64% of the high-DF
      sites (324 of 507) were on or adjacent to the ablation lines. Residual CFEs were
      observed in the infero-posterior regions in 83% of the patients. Almost half of
      the high-DF sites away from the linear ablation line were identified in the
      inferior (34%) and posterior (14%) LA regions. CONCLUSION: Linear ablation
      resulted in the localization of the continuous CFE regions and reduced the global
      LA DF in patients with persistent AF. This may be related to the proximity
      relationship between the linear ablation lines and high-DF sites except for in
      the infero-posterior regions.

PMID- 22956590
TI  - Exposure to diagnostic radiation and risk of breast cancer among carriers of
      BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK).
AB  - OBJECTIVE: To estimate the risk of breast cancer associated with diagnostic
      radiation in carriers of BRCA1/2 mutations. DESIGN: Retrospective cohort study
      (GENE-RAD-RISK). SETTING: Three nationwide studies (GENEPSO, EMBRACE, HEBON) in
      France, United Kingdom, and the Netherlands, PARTICIPANTS: 1993 female carriers
      of BRCA1/2 mutations recruited in 2006-09. MAIN OUTCOME MEASURE: Risk of breast
      cancer estimated with a weighted Cox proportional hazards model with a time
      dependent individually estimated cumulative breast dose, based on nominal
      estimates of organ dose and frequency of self reported diagnostic procedures. To
      correct for potential survival bias, the analysis excluded carriers who were
      diagnosed more than five years before completion of the study questionnaire.
      RESULTS: In carriers of BRCA1/2 mutations any exposure to diagnostic radiation
      before the age of 30 was associated with an increased risk of breast cancer
      (hazard ratio 1.90, 95% confidence interval 1.20 to 3.00), with a dose-response
      pattern. The risks by quarter of estimated cumulative dose <0.0020 Gy, >= 0.0020
      0.0065 Gy, >= 0.0066-0.0173 Gy, and >= 0.0174 Gy were 1.63 (0.96 to 2.77), 1.78
      (0.88 to 3.58), 1.75 (0.72 to 4.25), and 3.84 (1.67 to 8.79), respectively.
      Analyses on the different types of diagnostic procedures showed a pattern of
      increasing risk with increasing number of radiographs before age 20 and before
      age 30 compared with no exposure. A history of mammography before age 30 was also
      associated with an increased risk of breast cancer (hazard ratio 1.43, 0.85 to
      2.40). Sensitivity analysis showed that this finding was not caused by
      confounding by indication of family history. CONCLUSION: In this large European
      study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation
      before age 30 was associated with an increased risk of breast cancer at dose
      levels considerably lower than those at which increases have been found in other
      cohorts exposed to radiation. The results of this study support the use of non
      ionising radiation imaging techniques (such as magnetic resonance imaging) as the
      main tool for surveillance in young women with BRCA1/2 mutations.

PMID- 22956593
TI  - Impact of prior aspirin therapy on clinical manifestations of cardiovascular
      implantable electronic device infections.
AB  - AIMS: Cardiovascular implantable electronic device (CIED) infection may present
      as pocket infection or as infective endocarditis (CIED-IE) with vegetation on
      device leads or heart valves. As aspirin has both anti-inflammatory properties
      and interferes with platelet aggregation, we hypothesized that ongoing anti
      platelet therapy with aspirin may impact clinical and echocardiographic
      manifestations of CIED infection. METHODS AND RESULTS: We retrospectively
      reviewed 415 cases of CIED infection admitted to Mayo Clinic Rochester from 1991
      to 2008. Information regarding aspirin use was available in 392 (94.5%) cases and
      178 (45%) had received aspirin therapy prior to clinical onset of CIED infection.
      Although there were no significant differences in pathogen distribution between
      patients who had received prior aspirin therapy as compared with those who did
      not, patients on aspirin therapy were less likely to report chills (25% vs. 35%,
      P = 0.04), sweats (9% vs.18%, P = 0.01), or have peripheral leukocytosis on
      admission (33% vs. 46%, P = 0.005). Overall, 82 (21%) of 392 patients met the
      clinical criteria for CIED-IE. Patients on prior aspirin therapy were
      significantly less likely to have vegetations on CIED leads or heart valves than
      those who had not received it (15% vs. 26%, P = 0.01). However, despite the lower
      frequency of CIED-IE in the aspirin group, there was no significant difference (P
      = 0.97) in the overall survival between the two groups. CONCLUSION: Aspirin
      therapy prior to onset of CIED infection was associated with a lower likelihood
      of vegetation formation on CIED leads or heart valves and associated systemic
      manifestations of infection.

PMID- 22956594
TI  - Interobserver reliability of the chest radiograph in pulmonary embolism.
AB  - This study was sought to evaluate the interobserver agreement for interpreting
      the chest radiograph of patients with suspected acute pulmonary embolism (PE).
      The chest radiographs of 300 patients with clinically suspected acute PE were
      reviewed by 4 radiologists. Observers assessed the chest radiographic
      abnormalities and classified the chest radiograph as normal or abnormal. We found
      that the overall interobserver agreement was good for the exclusion of any
      pleural or parenchymal abnormality (k = 0.6; 95% CI: 0.56-0.64) but fair (k =
      0.28; 95% CI: 0.17-0.40) between junior radiologists when evaluating supine chest
      radiographs. The level of interobserver agreement for the interpretation of the
      chest radiograph as consistent or not with PE was fair (k = 0.24; 95% CI: 0.19
      0.29), regardless of the observer experience. In conclusion, chest radiography
      may be reliably used for targeting patients with suspected acute PE for different
      subsequent diagnostic investigations. 

PMID- 22956595
TI  - Effect of biological therapy on work participation in patients with ankylosing
      spondylitis: a systematic review.
AB  - OBJECTIVES: To review systematically the effect of biological treatment in
      patients with ankylosing spondylitis (AS) on three work outcomes: work status,
      absence from paid work and at-work productivity. METHODS: A systematic literature
      search was performed (Pubmed, Embase, Cochrane Library) to identify relevant
      articles. Risk of bias of included studies was assessed using the Cochrane
      guidelines for cohorts and randomised controlled trials (RCTs). Data were
      extracted using a self-composed data extraction form. Owing to extensive
      interstudy heterogeneity, narrative summaries were used to present the data.
      RESULTS: Nine studies were included (six uncontrolled cohorts, one population
      controlled cohort and two RCTs) that reported on 39 comparisons. Overall, 961
      patients were treated with three different tumour necrosis factor alpha
      inhibitors (etanercept, infliximab, adalimumab). For presenteeism and absence
      from work, most comparisons showed improvement in favour of biological agents,
      but not all comparisons were statistically significant and they usually concerned
      before-after analyses. For work status, changes were less often positive, but
      studies dealt with patients with longstanding AS, lacked power and had a
      relatively short follow-up. CONCLUSIONS: Although trends towards beneficial
      effects of biological agents in longstanding AS were seen on all work outcomes,
      the methodological limitations in the studies included hampers clear conclusions.
      Since the majority of studies were (extensions of) controlled trials, the
      generalisability of the effect of biological agents on work participation in real
      life should be further studied in larger (population-controlled) studies. The
      effect of biological agents in patients with early disease has not yet been
      examined.

PMID- 22956596
TI  - The US7 score is sensitive to change in a large cohort of patients with
      rheumatoid arthritis over 12 months of therapy.
AB  - PURPOSE: To determine the sensitivity to change of the US7 score among RA
      patients under various therapies and to analyze the effect of each therapeutic
      option over 1 year. To estimate predictors for development of destructive bone
      changes. METHODS: Musculoskeletal ultrasound (US7 score), DAS28, CRP and ESR were
      performed in 432 RA patients at baseline and after 3, 6 and 12 months. The cohort
      was divided into four sub-groups: first-line DMARDs (Group 1; 27.3%), therapy
      switch: DMARDs to second DMARDs (Group 2; 25.0%), first-line biologic after
      DMARDs therapy (Group 3; 35.4%) and therapy change from biologic to second
      biologic (Group 4; 12.3%). RESULTS: The US7 synovitis and tenosynovitis sum
      scores in grey-scale (GSUS) and power Doppler ultrasound (PDUS) as well as ESR,
      CRP decreased significantly (p<0.05) after 12 months in group 1 to 3. Group 1+2
      also illustrated a significant change of DAS28 after 1 year (p<0.001). Only in
      Group 4, the US7 erosion sum score decreased significantly from 4.3 to 3.6
      (p=0.008) after 1 year. Predictors capable of forecasting US erosions after one
      year were: higher score of US7 synovitis (p<0.001), of US7 erosions in GSUS
      (p<0.001), as well as of DAS28 (p<0.001) at baseline. CONCLUSIONS: The comparable
      developments of the US7 score with clinical and laboratory data illustrates its
      potential to reflect therapeutic response. Therefore, the novel US7 score is
      sensitive to change. Patients who switched from one biologic to another exhibited
      a significant decline in erosions after 12 months, while the erosions scores in
      the other groups were stable.

PMID- 22956597
TI  - Reasons for medical help-seeking behaviour of patients with recent-onset
      arthralgia.
AB  - OBJECTIVE: Patient delay in seeking medical help may cause suboptimal use of the
      therapeutic window in rheumatoid arthritis. We aimed to assess the motivations
      and the urgency with which patients with arthralgia seek medical help. METHODS:
      612 patients with arthralgia-visiting two Dutch Early Arthritis Recognition
      Clinics-were studied. Patients filled out a questionnaire with questions on their
      symptoms and their reasons for seeking medical help. Comparisons were made for
      patients with short or prolonged patient delay, patients with and without
      arthritis, age and gender. RESULTS: The median symptom duration was 4 weeks. A
      prolonged delay in seeking help was associated with a gradual onset of symptoms
      (78%) and the perception that symptoms would not be serious or would go away (16%
      and 48%, respectively). Arthralgia patients who promptly sought medical help more
      often had an acute onset of symptoms and more frequently reported impairments at
      work or in daily functioning than patients who postponed seeking help (all
      p<0.005). Patients with and without arthritis generally had similar reasons for
      seeking help. The proportion of patients who had a prolonged patient delay was
      comparable between male and female subjects and between age categories.
      Particularly younger patients postponed seeking help because they thought their
      symptoms would disappear spontaneously. CONCLUSIONS: This large-scale study
      observed several reasons and symptom characteristics influencing the help-seeking
      behaviour of persons with arthralgia. These data can be helpful to define
      strategies aiming at early identification of arthritis.

PMID- 22956598
TI  - Genome-wide association study meta-analysis of chronic widespread pain: evidence
      for involvement of the 5p15.2 region.
AB  - BACKGROUND AND OBJECTIVES: Chronic widespread pain (CWP) is a common disorder
      affecting ~10% of the general population and has an estimated heritability of 48
      52%. In the first large-scale genome-wide association study (GWAS) meta-analysis,
      we aimed to identify common genetic variants associated with CWP. METHODS: We
      conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of
      European descent, and replicated the effects of the genetic variants with
      suggestive evidence for association in 1480 CWP cases and 7989 controls.
      Subsequently, we studied gene expression levels of the nearest genes in two
      chronic inflammatory pain mouse models, and examined 92 genetic variants
      previously described associated with pain. RESULTS: The minor C-allele of
      rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1
      complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with
      a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to
      1.42, p=1.2*10(-8)). Combined with the replication, we observed a slightly
      attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7*10(-7)) with moderate
      heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed
      studies with joint-specific pain, the combined association was genome-wide
      significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4*10(-8), I2=0%). Expression
      levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the
      lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice
      without pain. None of the 92 genetic variants previously described were
      significantly associated with pain (p>7.7*10(-4)). CONCLUSIONS: We identified a
      common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in
      humans. This work suggests that CCT5 and FAM173B are promising targets in the
      regulation of pain.

PMID- 22956599
TI  - Evaluation of the genetic overlap between osteoarthritis with body mass index and
      height using genome-wide association scan data.
AB  - OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk
      factors for osteoarthritis. In addition, genetic overlap has been reported
      between osteoarthritis and normal adult height variation. We investigated whether
      this relationship is due to a shared genetic aetiology on a genome-wide scale.
      METHODS: We compared genetic association summary statistics (effect size, p
      value) for BMI and height from the GIANT consortium genome-wide association study
      (GWAS) with genetic association summary statistics from the arcOGEN consortium
      osteoarthritis GWAS. Significance was evaluated by permutation. Replication of
      osteoarthritis association of the highlighted signals was investigated in an
      independent dataset. Phenotypic information of height and BMI was accounted for
      in a separate analysis using osteoarthritis-free controls. RESULTS: We found
      significant overlap between osteoarthritis and height (p=3.3*10(-5) for signals
      with p<=0.05) when the GIANT and arcOGEN GWAS were compared. For signals with
      p<=0.001 we found 17 shared signals between osteoarthritis and height and four
      between osteoarthritis and BMI. However, only one of the height or BMI signals
      that had shown evidence of association with osteoarthritis in the arcOGEN GWAS
      was also associated with osteoarthritis in the independent dataset: rs12149832,
      within the FTO gene (combined p=2.3*10(-5)). As expected, this signal was
      attenuated when we adjusted for BMI. CONCLUSIONS: We found a significant excess
      of shared signals between both osteoarthritis and height and osteoarthritis and
      BMI, suggestive of a common genetic aetiology. However, only one signal showed
      association with osteoarthritis when followed up in a new dataset.

PMID- 22956600
TI  - Co-localisation of non-cartilaginous articular pathology increases risk of
      cartilage loss in the tibiofemoral joint--the MOST study.
AB  - PURPOSE: To assess risk of cartilage loss in the tibiofemoral joint in relation
      to baseline damage severity, and to analyse the association of nearby pathologic
      findings on the risk of subsequent cartilage loss. METHODS: The Multicenter
      Osteoarthritis Study is a longitudinal study of individuals with or at high risk
      for knee osteoarthritis. MRI examinations were assessed according to the Whole
      Organ MRI Score. Included were all knees with available baseline and 30 months
      MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in
      each subregion in relation to the number of associated articular features
      including bone marrow lesions, meniscal damage and extrusion and also in regard
      to baseline damage severity, respectively. RESULTS: 13 524 subregions of 1365
      knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage
      at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow
      up. Risk of cartilage loss was increased for subregions with associated features
      (OR 2.53, 95% CI 2.03 to 3.15 for one, 4.32 95% CI 3.42 to 5.47 for two and 5.30
      95% CI 3.95 to 7.12 for three associated features; p for trend<0.0001).
      Subregions with prevalent cartilage damage showed increased risk for further
      cartilage loss compared to subregions with intact cartilage at baseline with
      small superficial defects exhibiting highest risk. CONCLUSIONS: Risk of cartilage
      loss is increased for subregions with associated pathology and further increased
      when more than one type of associated feature is present. In addition, prevalent
      cartilage damage increases risk for subsequent cartilage loss.

PMID- 22956601
TI  - Effect of histamine on Ca(2+)-dependent signaling pathways in rat conjunctival
      goblet cells.
AB  - PURPOSE: The purpose of this study was to determine the Ca(2+)-dependent cellular
      signaling pathways used by histamine to stimulate conjunctival goblet cell
      secretion. METHODS: Cultured rat goblet cells were grown in RPMI 1640. Goblet
      cell secretion of high molecular weight glycoconjugates was measured by an enzyme
      linked lectin assay. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured by loading
      cultured cells with the Ca(2+) sensitive dye fura-2. The level of [Ca(2+)](i) was
      measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2
      was depleted using small interfering RNA (siRNA). RESULTS: Histamine-stimulated
      conjunctival goblet cell secretion of high molecular weight glycoproteins was
      blocked by removal of extracellular Ca(2+) and depletion of ERK2 by siRNA.
      Histamine increase in [Ca(2+)](i) was desensitized by repeated addition of
      agonist and blocked by a phospholipase C antagonist. Histamine at higher doses
      increased [Ca(2+)](i) by stimulating influx of extracellular Ca(2+), but at a
      lower dose released Ca(2+) from intracellular stores. Activation of each
      histamine receptor subtype (H(1)-H(4)) increased [Ca(2+)](i) and histamine
      stimulation was blocked by antagonists of each receptor subtype. The H(2)
      receptor subtype increase in [Ca(2+)](i) was cAMP dependent. CONCLUSIONS: We
      conclude that histamine activates phospholipase C to release intracellular Ca(2+)
      that induces the influx of extracellular Ca(2+) and activates ERK1/2 to stimulate
      conjunctival goblet cell mucous secretion, and that activation of all four
      histamine receptor subtypes can increase [Ca(2+)](i).

PMID- 22956603
TI  - SEMA4A mutations lead to susceptibility to light irradiation, oxidative stress,
      and ER stress in retinal pigment epithelial cells.
AB  - PURPOSE: RP is a retinal degeneration disorder that is caused by mutations of
      various genes, including semaphorin-4A (SEMA4A). A number of retinal diseases,
      including RP, are associated with light exposure, oxidative stress, and
      endoplasmic reticulum (ER) stress. In this study, we investigated whether mutant
      SEMA4A causes retinal dysfunction via light exposure, oxidative stress, and ER
      stress. METHODS: Mutant SEMA4A (D345H or F350C) was overexpressed in a human
      retinal epithelium cell line ARPE19. Intracellular localization of mutant SEMA4A
      was investigated using confocal laser scanning microscopy. The ARPE-19 cells were
      also irradiated with white light, and expression of 78 kDa glucose-regulated
      protein (GRP78), a marker of ER stress, and phagocytosis were measured. The cells
      were treated with an ER stress inducer, tunicamycin, or an oxidative stressor,
      H(2)O(2), and cell death was measured. Human SEMA4A mutants were expressed in
      zebrafish embryos with tunicamycin and mRNA of DNA damage-inducible transcript 3
      (ddit3) was measured as an ER stress marker. RESULTS: Mutant SEMA4A was localized
      in the ER, whereas wild type (WT) SEMA4A was observed in cell membranes. The
      expression of GRP78 was increased by mutant SEMA4A following light irradiation,
      and phagocytosis was suppressed in mutant SEMA4A-transfected cells. Mutant SEMA4A
      induced susceptibility to ER stress and oxidative stress. In zebrafish, human
      mutant SEMA4A increased ddit3 mRNA compared with WT under the ER stress
      condition. CONCLUSIONS: Our results suggest that mutations in SEMA4A may cause
      susceptibility to light exposure, oxidative stress, and ER stress, which may be
      involved in the progression and pathology of RP.

PMID- 22956602
TI  - Selective activation of ATF6 and PERK endoplasmic reticulum stress signaling
      pathways prevent mutant rhodopsin accumulation.
AB  - PURPOSE: Many rhodopsin mutations that cause retinitis pigmentosa produce
      misfolded rhodopsin proteins that are retained within the endoplasmic reticulum
      (ER) and cause photoreceptor cell death. Activating transcription factor 6 (ATF6)
      and protein kinase RNA-like endoplasmic reticulum kinase (PERK) control
      intracellular signaling pathways that maintain ER homeostasis. The aim of this
      study was to investigate how ATF6 and PERK signaling affected misfolded rhodopsin
      in cells, which could identify new molecular therapies to treat retinal diseases
      associated with ER protein misfolding. METHODS: To examine the effect of ATF6 on
      rhodopsin, wild-type (WT) or mutant rhodopsins were expressed in cells expressing
      inducible human ATF6f, the transcriptional activator domain of ATF6. Induction of
      ATF6f synthesis rapidly activated downstream genes. To examine PERK's effect on
      rhodopsin, WT or mutant rhodopsins were expressed in cells expressing a
      genetically altered PERK protein, Fv2E-PERK. Addition of the dimerizing molecule
      (AP20187) rapidly activated Fv2E-PERK and downstream genes. By use of these
      strategies, it was examined how selective ATF6 or PERK signaling affected the
      fate of WT and mutant rhodopsins. RESULTS: ATF6 significantly reduced T17M, P23H,
      Y178C, C185R, D190G, K296E, and S334ter rhodopsin protein levels in the cells
      with minimal effects on monomeric WT rhodopsin protein levels. By contrast, the
      PERK pathway reduced both levels of WT, mutant rhodopsins, and many other
      proteins in the cell. CONCLUSIONS: This study indicates that selectively
      activating ATF6 or PERK prevents mutant rhodopsin from accumulating in cells.
      ATF6 signaling may be especially useful in treating retinal degenerative diseases
      arising from rhodopsin misfolding by preferentially clearing mutant rhodopsin and
      abnormal rhodopsin aggregates.

PMID- 22956604
TI  - Epithelial-mesenchymal transition-like phenotypic changes of retinal pigment
      epithelium induced by TGF-beta are prevented by PPAR-gamma agonists.
AB  - PURPOSE: Proliferative eye diseases, such as proliferative vitreoretinopathy and
      proliferative diabetic retinopathy, are caused partly by fibrotic change of
      retinal pigment epithelial cells (RPECs). The purpose of our study was to examine
      the effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      agonist on the fibrotic change of primate RPECs. METHODS: Monkey RPECs (MRPECs)
      isolated from a cynomolgus monkey eye were subcultured. To induce fibrotic
      change, MRPECs were cultured with TGF-beta2 (3 ng/mL), and also cultured in the
      coexistence of TGF-beta2 and the PPAR-gamma agonist pioglitazone (30 MUM). The
      phenotype of the cultured MRPECs was evaluated by phase contrast microscopy and
      immunocytochemical analysis. The phosphorylation of Smad2/Smad3 proteins was
      examined by Western blot analysis. RESULTS: Primary MRPECs were cultured as a
      monolayer with a hexagonal cell shape, and positive expression of ZO-1,
      Na(+)/K(+)-ATPase, and RPE65 was confirmed. Cell morphology and the expression of
      these markers were maintained in the presence of pioglitazone, whereas the cells
      were elongated and the expression of these markers was reduced in its absence.
      Conversely, the expression of phalloidin, alpha-smooth muscle actin, and
      fibronectin was reduced in the presence of pioglitazone, whereas it was increased
      in the absence. Western blot assay demonstrated that phosphorylation of
      Smad2/Smad3 proteins was suppressed by pioglitazone. CONCLUSIONS: The PPAR-gamma
      agonist pioglitazone inhibited the fibrotic change of primary MRPECs through the
      suppression of TGF-beta signaling. Pioglitazone might prove to be a clinically
      applicable and effective pharmaceutic treatment for proliferative eye diseases.

PMID- 22956605
TI  - Prevalence of and risk factors for pterygium in rural adult chinese populations
      of the Bai nationality in Dali: the Yunnan Minority Eye Study.
AB  - PURPOSE: The purpose of the study was to describe the prevalence, severity, and
      associated risk factors for pterygium in a population-based sample of rural
      residents of the Bai minority population in rural Dali, China. METHODS: A
      population-based survey of Chinese Bai Nationality aged >=50 years from randomly
      selected block groups in southwestern China was conducted. A clinical examination
      by experienced ophthalmologists was carried out, and the presence of pterygium
      was diagnosed at the examination. Pterygium was graded clinically by slit lamp
      examination. Questionnaires were conducted on risk factors. RESULTS: From a total
      of 2742 eligible subjects, 2133 (77.8%) were examined. The prevalence of
      pterygium was high (overall 39.0% [95% confidence interval (CI) 37.0-41.0]).
      Women had a higher rate than men (27.3% vs. 11.7%, respectively). In multivariate
      analysis, pterygium was independently associated with increasing age (odds ratio
      [OR] 1.55 [95% CI 1.24-1.93], 1.47 [95% CI 1.13-1.91], and 1.79 [95% CI 1.17
      2.73], respectively, for persons 60-69 years, 70-79 years, and 80 years and older
      compared with 50-59 years), female sex (OR 1.42 [95% CI 1.08-1.88]), lack of
      formal education (OR 1.26 [95% CI 1.03-1.56]), and presence of outdoor work (OR
      1.51 [95% CI 1.10-1.92]). Height, weight, hypertension, diabetes, smoking, and
      alcohol use history were not associated with pterygium. CONCLUSIONS: The
      prevalence of pterygium in Dali is 39.0% among Chinese Bai aged 50 years and
      older. Independent associations with increasing age (>59 years), female sex, lack
      of education, and occupations linked to outdoor work suggest a multifactorial
      cause of this condition.

PMID- 22956606
TI  - Mass spectrometric analyses of phosphatidylcholines in alkali-exposed corneal
      tissue.
AB  - PURPOSE: The aims were to determine whether exposure to sodium hydroxide results
      in predictable changes in phosphatidylcholine (PC) in corneal tissue and if PC
      profile changes correlate to exposure duration. PCs are major components of the
      cell membrane lipid bilayer and are often involved in biological processes such
      as signaling. METHODS: Enucleated porcine (n = 140) and cadaver human eyes (n =
      20) were exposed to water (control) and 11 M NaOH. The corneas were excised and
      lipids were extracted using the Bligh and Dyer method with suitable
      modifications. Class-specific lipid identification was carried out using a
      ratiometric lipid standard on a TSQ Quantum Access Max mass spectrometer. Protein
      amounts were determined using Bradford assays. RESULTS: Control and alkali
      treated corneas showed reproducible PC spectra for both porcine and human
      corneas. Over 200 PCs were identified for human and porcine control and each
      experimental time point. Several PC species (m/z values) consequent upon alkali
      exposure could not be ascribed to a recorded PC species. Control and treated
      groups showed 41 and 29 common species among them for porcine and human corneas,
      respectively. The unique PC species peaked at 12 minutes and at 30 minutes for
      human and porcine corneas followed by a decline consistent with an interplay of
      alkali penetration and hydrolyses at various time points. CONCLUSIONS: Alkali
      exposure dramatically changes the PC profile of cornea. Our data are consistent
      with penetration and hydrolysis as stochastic contributors to changes in PCs due
      to exposure to alkali for a finite duration and amount.

PMID- 22956607
TI  - Endothelial Cdkn1a (p21) overexpression and accelerated senescence in a mouse
      model of Fuchs endothelial corneal dystrophy.
AB  - PURPOSE: Stress of the endoplasmic reticulum and oxidative stress play critical
      roles in the pathogenesis of Fuchs Endothelial Corneal Dystrophy (FECD). In the
      normal aging cornea, cellular stress has been associated with a loss in
      proliferative capacity (premature senescence) of corneal endothelial cells
      (CECs). The present study used a transgenic Col8a2(Q455K/Q455K) knock-in mouse
      model of early-onset FECD to identify the endothelial expression profile of
      specific cellular stress response-related targets, which may be relevant to late
      onset FECD. METHODS: The differential endothelial mRNA levels of cellular stress
      response-related genes were determined in 12-month-old homozygous
      Col8a2(Q455K/Q455K) mutant and wild-type mice using customized PCR arrays. Result
      validation and analysis of additional senescence-related transcripts was
      performed by real-time PCR. Expression of p53 and p21 was assessed by
      immunofluorescence. Senescence-associated beta-galactosidase (SA-beta-Gal)
      activity was investigated by histochemical labeling. Human FECD samples and
      normal controls were examined for p21 expression by immunohistochemistry.
      RESULTS: PCR-array analysis showed greater than 2-fold and/or significantly
      altered endothelial regulation of 19 cellular stress response-related transcripts
      in Col8a2(Q455K/Q455K) mutant mice; real-time PCR documented statistically
      significant upregulation of senescence-associated targets Cdkn1a (p21), Serpine1
      (PAI-1), Tagln (Sm22), Fn1 and Clu (ApoJ). Immunofluorescence revealed increased
      expression of nuclear p53 and p21 in mutant animals. SA-beta-Gal staining
      detected increased proportions of senescent CECs in mutant mice. Human FECD
      endothelium exhibited increased levels of nuclear p21 protein. CONCLUSIONS: Our
      results identify endothelial Cdkn1a (p21) upregulation in a mouse model of early
      onset FECD, confirm overexpression of p21 in late-onset human FECD endothelium,
      and suggest a role for premature senescence in FECD.

PMID- 22956609
TI  - Photoreceptor layer regeneration is detectable in the human retina imaged by SD
      OCT after laser treatment using subthreshold laser power.
AB  - PURPOSE: We evaluated the morphologic changes in retinal structure after laser
      photocoagulation using supra- and subthreshold laser fluence. METHODS: In a
      prospective cohort study 10 consecutive patients received scatter laser
      photocoagulation. Treatment was performed using a semiautomated patterned
      scanning laser system. In a study area adjacent to the temporal vessel arcades, 2
      * 2 pattern laser spots were applied with halving the flux of the laser power in
      a stepwise manner starting from a power producing a typical grayish lesion. The
      study areas then were imaged on days one, three, and seven, and on months one,
      two, three, and six using color fundus photography, autofluorescence (AF),
      infrared (IR) imaging, and spectral domain optical coherence tomography (SD-OCT).
      RESULTS: The starting threshold power lesions each were visible on color fundus
      photography, IR, and AF in all patients, and showed characteristic changes on OCT
      throughout the follow-up period. The halved flux laser burns (first step) were
      undetectable ophthalmoscopically during the laser session, but during the follow
      up always were detectable on IR and AF images, and sometimes on fundus
      photography. On OCT they showed changes similar to the suprathreshold laser
      scars, but were much smaller in diameter, and in some instances an inward
      migration of the photoreceptor layer was observed. CONCLUSIONS: Subthreshold
      laser burns with halved energy flux produced similar morphologic changes in the
      retina as threshold power, but with a smaller size. They induced less collateral
      damage to the neuroretina, and permit a level of reorganization in the outer
      retina. (ClinicalTrials.gov number, NCT00682240.).

PMID- 22956608
TI  - Existence of the canonical Wnt signaling pathway in the human trabecular
      meshwork.
AB  - PURPOSE: We previously discovered elevated levels of secreted frizzled-related
      protein 1 (sFRP1), the Wnt signaling pathway inhibitor, in the glaucomatous
      trabecular meshwork (GTM), and found that key canonical Wnt signaling pathway
      genes are expressed in the trabecular meshwork (TM). The purpose of our study was
      to determine whether a functional canonical Wnt signaling pathway exists in the
      human TM (HTM). METHODS: Western immunoblotting and/or immunofluorescent
      microscopy were used to study beta-catenin translocation as well as the actin
      cytoskeleton in transformed and primary HTM cells. A TCF/LEF luciferase assay was
      used to study functional canonical Wnt signaling, which was confirmed further by
      WNT3a-induced expression of a pathway target gene, AXIN2, via quantitative PCR.
      Intravitreal injection of an Ad5 adenovirus expressing Dickkopf-related protein-1
      (DKK1) was used to study the in vivo effect of canonical Wnt signaling on IOP in
      mice. RESULTS: WNT3a induced beta-catenin translocation in the HTM, which was
      blocked by co-treatment with sFRP1. Similarly, WNT3a enhanced luciferase levels
      in TCF/LEF luciferase assays, which also were blocked by sFRP1. Furthermore,
      AXIN2 expression was elevated significantly by WNT3a. However, neither WNT3a nor
      sFRP1 affected actin cytoskeleton organization, which theoretically could be
      regulated by noncanonical Wnt signaling in HTM cells. Exogenous DKK1, a specific
      inhibitor for the canonical Wnt signaling pathway, or sFRP1 elevated mouse IOP to
      equivalent levels. CONCLUSIONS: There is a canonical Wnt signaling pathway in the
      TM, and this canonical Wnt pathway, but not the noncanonical Wnt signaling
      pathway, regulates IOP.

PMID- 22956610
TI  - Heparanase and vascular endothelial growth factor expression is increased in
      hypoxia-induced retinal neovascularization.
AB  - PURPOSE: Heparanase and VEGF are related closely to angiogenesis in cancer. The
      purpose of our study was to evaluate the expression and correlation of heparanase
      and VEGF in hypoxia-induced retinal neovascularization. METHODS: C57BL/6 oxygen
      induced retinopathy (OIR) mice and human retinal microvascular endothelial cells
      (HRECs) were treated with the hypoxia mimetic agent cobalt chloride (CoCl2), and
      in the presence of the heparanase inhibitor phosphomannopentaose sulfate
      (Muparfostat, PI-88). Heparanase activity was assayed in HRECs, and the
      expression of heparanase, VEGF protein and mRNA were evaluated by
      immunofluorescence, ELISA, Western blot, and real-time PCR while retinal flat
      mounts were used to evaluate the area of neovascularization of mice retina.
      RESULTS: HREC heparanase activity was increased by treatment with CoCl2, but was
      decreased by PI-88. Immunofluorescence showed that heparanase and VEGF staining
      was intense in hypoxia-treated HRECs and OIR mice retina, while VEGF staining was
      faint in the normoxia and PI-88-treated ones. Western blot and real-time PCR
      results indicated that the expression of heparanase and VEGF was increased under
      hypoxic conditions, and the increase of VEGF was inhibited by PI-88. Retinal flat
      mounts showed that the area of new vessels in retina of OIR mice was increased
      compared to the normoxic mice, and this effect was inhibited by PI-88.
      CONCLUSIONS: Heparanase is upregulated and associated with the VEGF expression in
      hypoxia-induced retinal diseases. Heparanase is involved in hypoxia-induced
      neovascularization through promoting VEGF expression and may be a new therapeutic
      target for hypoxia-induced neovascularization retinal diseases.

PMID- 22956611
TI  - Human lamina cribrosa insertion and age.
AB  - PURPOSE: To test the hypothesis that in healthy human eyes the lamina cribrosa
      (LC) insertion into the pia mater increases with age. METHODS: The optic nerve
      heads (ONHs) of donor eyes fixed at either 5 or 50 mm Hg of IOP were sectioned,
      stained, and imaged under bright- and dark-field conditions. A 3-dimensional (3D)
      model of each ONH was reconstructed. From the 3D models we measured the area of
      LC insertion into the peripapillary scleral flange and into the pia, and computed
      the total area of insertion and fraction of LC inserting into the pia. Linear
      mixed effect models were used to determine if the measurements were associated
      with age or IOP. RESULTS: We analyzed 21 eyes from 11 individuals between 47 and
      91 years old. The LC inserted into the pia in all eyes. The fraction of LC
      inserting into the pia (2.2%-29.6%) had a significant decrease with age (P =
      0.049), which resulted from a nonsignificant increase in the total area of LC
      insertion (P = 0.41) and a nonsignificant decrease in the area of LC insertion
      into the pia (P = 0.55). None of the measures was associated with fixation IOP (P
      values 0.44-0.81). Differences between fellow eyes were smaller than differences
      between unrelated eyes. CONCLUSIONS: The LC insertion into the pia mater is
      common in middle-aged and older eyes, and does not increase with age. The
      biomechanical and vascular implications of the LC insertion into the pia mater
      are not well understood and should be investigated further.

PMID- 22956612
TI  - Choroidal thickness in unilateral advanced glaucoma.
AB  - PURPOSE: To investigate whether choroidal thickness measured using optical
      coherence tomography (OCT) in eyes with advanced glaucoma differs from that of
      fellow eyes with no or mild glaucoma. METHODS: Thirty-six patients with advanced
      glaucoma in one eye and with no glaucoma or mild glaucoma in the fellow eye
      underwent macular scanning using enhanced depth imaging OCT. Average, subfoveal,
      nasal, and temporal choroidal thicknesses were compared between severely affected
      and fellow eyes after adjusting for axial length and intraocular pressure.
      RESULTS: There were no significant differences between choroidal thickness
      measurements in eyes with advanced glaucoma and those in fellow eyes (P = 0.78 to
      0.99). Based on average and subfoveal choroidal thicknesses, the choroid of eyes
      with advanced glaucoma was thicker than that of fellow eyes in 2.8% and 2.8% of
      the patients, whereas the choroid of fellow eyes was thicker than that of eyes
      with advanced glaucoma in 5.6% and 8.3% of the patients (P = 0.55 and 0.30,
      respectively). Neither eye had a consistently thinner or thicker choroid.
      Stepwise multiple regression analysis also showed no differences between
      choroidal thicknesses of severely affected eyes and those of fellow eyes (all P >
      0.05). Factors associated with a thinner choroid were aging (28.6 MUm per decade,
      P < 0.001) and increasing axial length (21.4 MUm/mm, P < 0.001). Visual field
      mean deviation did not correlate with choroidal thickness measurements.
      CONCLUSIONS: There was no significant change in choroidal thickness of eyes with
      advanced open-angle glaucoma compared to that of fellow eyes with no glaucoma or
      with mild glaucoma. A thinner choroid does not necessarily indicate the presence
      of glaucoma, nor is a thicker choroid necessarily a surrogate for the absence of
      glaucoma. These observations further suggest a lack of relationship between open
      angle glaucoma and choroidal thickness.

PMID- 22956613
TI  - Does partial occlusion promote normal binocular function?
AB  - PURPOSE: There is growing evidence that abnormal binocular interactions play a
      key role in the amblyopia syndrome and represent a viable target for treatment
      interventions. In this context the use of partial occlusion using optical devices
      such as Bangerter filters as an alternative to complete occlusion is of
      particular interest. The aims of this study were to understand why Bangerter
      filters do not result in improved binocular outcomes compared to complete
      occlusion, and to compare the effects of Bangerter filters, optical blur and
      neutral density (ND) filters on normal binocular function. METHODS: The effects
      of four strengths of Bangerter filters (0.8, 0.6, 0.4, 0.2) on letter and vernier
      acuity, contrast sensitivity, stereoacuity, and interocular suppression were
      measured in 21 observers with normal vision. In a subset of 14 observers, the
      partial occlusion effects of Bangerter filters, ND filters and plus lenses on
      stereopsis and interocular suppression were compared. RESULTS: Bangerter filters
      did not have graded effect on vision and induced significant disruption to
      binocular function. This disruption was greater than that of monocular defocus
      but weaker than that of ND filters. The effect of the Bangerter filters on
      stereopsis was more pronounced than their effect on monocular acuity, and the
      induced monocular acuity deficits did not predict the induced deficits in
      stereopsis. CONCLUSIONS: Bangerter filters appear to be particularly disruptive
      to binocular function. Other interventions, such as optical defocus and those
      employing computer generated dichoptic stimulus presentation, may be more
      appropriate than partial occlusion for targeting binocular function during
      amblyopia treatment.

PMID- 22956614
TI  - Validity, reliability, and repeatability of the useful field of view test in
      persons with normal vision and patients with glaucoma.
AB  - PURPOSE: To determine the validity, test-retest reliability and repeatability of
      the UFOV test in healthy controls and glaucoma patients. METHODS: Three
      substudies with the UFOV test were conducted: (1) validity was evaluated in 77
      older controls (mean age 64 [SD, 7] years) and 53 glaucoma patients (mean age 69
      [SD, 8] years); (2) test-retest reliability was evaluated in 13 young controls
      (mean age 28 [SD, 4] years), 21 older controls (mean age 66 [SD, 9] years), and
      22 glaucoma patients (mean age 68 [SD, 8] years) who performed the test twice
      within approximately two weeks; (3) repeatability was evaluated in 17 young
      controls (mean age 33 [SD, 8] years) who performed the test five times on the
      same day. RESULTS: In the validity substudy, mean total processing time was
      significantly less for older controls (358.3 ms [SD, 226.8 ms]), than glaucoma
      patients (580.2 ms [SD, 324.5 ms]), with moderate correlations (rho >= 0.40)
      between total processing time and age, and visual field impairment. In the
      reliability substudy, mean total processing time was significantly less on retest
      (P <= 0.02), with glaucoma patients showing the largest mean test-retest
      difference (144.7 ms [SD, 168.9 ms]) compared with young (31.5 ms [SD, 43.7 ms])
      and older controls (56.2 ms [SD, 74.8 ms]). The 95% limits of agreement were
      significantly wider for glaucoma patients (-186.3 and +475.7 ms) compared with
      young (-54.1 and +117.1 ms) and older controls (-90.5 and +202.9 ms), (P < 0.01).
      In the repeatability substudy, performance remained constant after the second of
      five tests (differences in mean total processing time <6 ms). CONCLUSIONS:
      Measurement properties of the UFOV test are important for assessing functional
      performance, in particular, fitness to drive. Our results indicate moderate
      variability, greater for glaucoma patients than healthy controls, and a learning
      effect. Two consecutive tests are suggested to establish reliable baseline
      measures.

PMID- 22956615
TI  - A model to measure fluid outflow in rabbit capsules post glaucoma implant
      surgery.
AB  - PURPOSE: Prior models of glaucoma filtration surgery assess bleb morphology,
      which does not always reflect function. Our aim is to establish a model that
      directly measures tissue hydraulic conductivity of postsurgical outflow in rabbit
      bleb capsules following experimental glaucoma filtration surgery. METHODS: Nine
      rabbits underwent insertion of a single-plate pediatric Molteno implant into the
      anterior chamber of their left eye. Right eyes were used as controls. The rabbits
      were then allocated to one of two groups. Group one had outflow measurements
      performed at 1 week after surgery (n = 5), and group two had measurements
      performed at 4 weeks (n = 4). Measurements were performed by cannulating the
      drainage tube ostium in situ with a needle attached to a pressure transducer and
      a fluid column at 15 mm Hg. The drop in the fluid column was measured every
      minute for 5 minutes. For the control eyes (n = 6), the anterior chamber of the
      unoperated fellow eye was cannulated. Animals were euthanized with the implant
      and its surrounding capsule dissected and fixed in 4% paraformaldehyde, and
      embedded in paraffin before 6-MUm sections were cut for histologic staining.
      RESULTS: By 7 days after surgery, tube outflow was 0.117 +/- 0.036 MUL/min/mm Hg
      at 15 mm Hg (mean +/- SEM), whereas at 28 days, it was 0.009 +/- 0.003 MUL/min/mm
      Hg. Control eyes had an outflow of 0.136 +/- 0.007 MUL/min/mm Hg (P = 0.004, one
      way ANOVA). Hematoxylin and eosin staining demonstrated a thinner and looser
      arrangement of collagenous tissue in the capsules at 1 week compared with that at
      4 weeks, which had thicker and more densely arranged collagen. CONCLUSIONS: We
      describe a new model to directly measure hydraulic conductivity in a rabbit
      glaucoma surgery implant model. The principal physiologic endpoint of glaucoma
      surgery can be reliably quantified and consistently measured with this model. At
      28 days post glaucoma filtration surgery, a rabbit bleb capsule has significantly
      reduced tissue hydraulic conductivity, in line with loss of implant outflow
      facility, and increased thickness and density of fibrous encapsulation.

PMID- 22956616
TI  - Reactive oxygen species regulate prosurvival ERK1/2 signaling and bFGF expression
      in gliosis within the retina.
AB  - PURPOSE: Gliosis is the response of glial cells within retinal tissue to injury.
      It can be beneficial in the short term, but if the response is extended it can
      lead to scar formation, which contributes to blindness. Phosphorylation of
      extracellular signal regulated kinase 1/2 (ERK1/2) is considered to be a hallmark
      event of gliosis, but the factors involved throughout its associated signaling
      pathway remain poorly understood, particularly in the retina. Because reactive
      oxygen species (ROS) can inhibit phosphatases, thereby altering the
      phosphorylation of proteins, this study tested the hypothesis that ROS regulate
      the phosphorylation of ERK1/2 (pERK1/2) in gliosis. METHODS: Increases in pERK1/2
      were detected using Western blotting and immunofluorescence in three models of
      retinal stress, specifically the in vivo light induction, the rd1 disease, and
      the ex vivo retinal explant models. Explanted murine retinas were used to
      identify the signaling partners of pERK1/2 via Western blotting, in conjunction
      with inhibitors. The effect of this pathway on cell death was measured with
      terminal dUTP nick end labeling. RESULTS: It was demonstrated that several
      inhibitors of ROS greatly reduce the levels of pERK1/2 in the somata of Muller
      cells and furthermore decrease two other downstream signaling events: the
      phosphorylation of STAT3 and the upregulation of basic fibroblast growth factor.
      Using the specific inhibitor of ERK1/2, UO126, the resultant outcomes of this
      signaling pathway were determined to contribute significantly to cell survival.
      CONCLUSIONS: The novel finding of this study that ROS contribute to a prosurvival
      signaling pathway in retinal Muller cell gliosis indicates that some degree of
      caution should be used when considering antioxidants as therapeutics.

PMID- 22956617
TI  - Visualization of the optic fissure in short-wavelength autofluorescence images of
      the fundus.
AB  - PURPOSE: To document and explain the presence, inferior to the optic disc, of a
      distinct vertical boundary between two retinal areas of different short
      wavelength autofluorescence (SW-AF) intensities. METHODS: SW-AF images of the
      inferonasal region were acquired from 32 healthy subjects. Additionally, color,
      488-nm reflectance (488-R), near-infrared reflectance (NIR-R), NIR
      autofluorescence (NIR-AF) images, and a spectral domain optical coherence
      tomography (SD-OCT) image were obtained in selected subjects. Gray levels (GL) on
      both sides of the demarcation line were measured in SW-AF and 488-R at fixed
      distances from the disc center. RESULTS: A curved demarcation line inferior to
      the optic disc was observed on SW-AF images in 31/32 subjects. AF levels on the
      nasal side were 13% (+/-6%) lower than on the temporal side at 20 degrees 
      inferior to the disc center. The contrast between the nasal and the temporal
      areas was not significantly affected by age, sex, refractive error, race, or iris
      color. The demarcation line visible in SW-AF was also seen, though with reduced
      contrast, in approximately 80% of the 488-R images (lower reflectance on the
      nasal side) and 50% of color images. The boundary was not detected by NIR-R, NIR
      AF, or by SD-OCT imaging. CONCLUSIONS: The location and the distinctness of the
      demarcation line may indicate a relationship to the closed embryonic optic
      fissure. The reduced SW-AF intensity and 488-R reflectance observed on the nasal
      side of this line may be attributable to lower lipofuscin and melanin content per
      unit area, possibly resulting from a difference in RPE cell shape.

PMID- 22956618
TI  - The effect of monocyte chemoattractant protein-1/CC chemokine ligand 2 on aqueous
      humor outflow facility.
AB  - PURPOSE: To investigate the effect of monocyte chemoattractant protein-1 (MCP
      1)/CC chemokine ligand 2 on aqueous humor outflow facility. METHODS: Aqueous
      humor outflow facility was measured in enucleated porcine eyes in a constant
      pressure perfusion system with or without MCP-1 (1600 ng/mL). Expression of CCR2,
      an MCP-1 receptor, in Schlemm's canal endothelial (SCE) cells was examined by
      reverse transcription-polymerase chain reaction (RT-PCR) assay. The effect of MCP
      1 (0-1600 ng/mL) on SCE cell viability was evaluated using a WST-8 assay. The
      effect of MCP-1 (0-800 ng/mL) on SCE-cell monolayer permeability was evaluated
      with or without a CCR2 antagonist (10 nM) by measuring transendothelial
      electrical resistance (TEER). The intracellular localization of the gap junction
      protein ZO-1 was analyzed by immunofluorescence staining of SCE cells. RESULTS:
      The aqueous humor outflow facility increased significantly from basal levels at
      80 minutes after perfusion with MCP-1 compared with control eyes (21.2% +/- 6.6%
      [MCP-1] vs. 5.7 +/- 2.5% [control]; P = 0.048). CCR2 was detected by RT-PCR. Cell
      viability was not affected by MCP-1 treatment. TEER of SCE-cell monolayer at 3
      hours after treatment with 800 ng/mL MCP-1 decreased by 21.6 +/- 1.7% compared
      with controls (P = 0.014), and the TEER-decreasing effects of MCP-1 were
      attenuated by a CCR2 antagonist. Immunocytochemical staining revealed a modest
      disruption of ZO-1 in MCP-1-treated SCE cells. CONCLUSIONS: The present results
      revealed that MCP-1 increased aqueous humor outflow facility and decreased TEER
      via CCR2. These findings suggest that MCP-1 modulates aqueous humor outflow
      through the conventional pathway.

PMID- 22956619
TI  - Retinal function and morphology in monkeys with ethambutol-induced optic
      neuropathy.
AB  - PURPOSE: Ethambutol-induced optic neuropathy is a well recognized adverse ocular
      event. However, abnormalities of the retina in this optic neuropathy are not
      fully understood. Therefore, the purpose of the present study was to investigate
      both functional and morphological alterations of the retina induced by ethambutol
      in monkeys. METHODS: Ethambutol was orally administered to three cynomolgus
      monkeys, initially at 400 mg/kg/day followed by 800 mg/kg/day, for a maximum of
      39 weeks. Full-field electroretinograms (ERGs) were recorded at intervals of
      approximately one month. The protocol included standard ERG responses to white
      flashes obtained under dark-adapted conditions (rod, combined rod-cone,
      oscillatory potentials) or with a white background (single-flash cone, 30 Hz
      flicker). In addition, we measured the ERG elicited with red flashes under blue
      background light (single-flash cone response [R/B]). All the ethambutol-treated
      monkeys were euthanized, and the retinae and various other nervous system tissues
      were examined histopathologically. RESULTS: No obvious changes were observed in
      the standard full-field ERGs. On the other hand, selective attenuation of the
      photopic negative response (PhNR) of the single-flash cone response (R/B) was
      observed in two out of three ethambutol-treated monkeys at week 22 or 28.
      Histopathology of these two monkeys revealed single cell necrosis of the retinal
      ganglion cells (RGCs), decreased RGCs in the parafovea and increased microglial
      cells in the nerve fiber layer in the retina, in addition to demyelination and
      glial reaction in the optic nerve, chiasm and tracts. CONCLUSIONS: The attenuated
      PhNR and histopathology of the retina indicated that RGCs were markedly damaged,
      both functionally and morphologically in monkeys with ethambutol-induced optic
      neuropathy. These results implied that RGCs are predominantly affected in the
      retina of patients with ethambutol-induced optic neuropathy.

PMID- 22956621
TI  - Food restriction alters villi morphology in obese rats: gut mechanism for weight
      regain?
AB  - Weight regain after a long-term weight-loss program is a greater problem in
      obesity treatment than is weight reduction. Hence, the gut may elevate the
      absorption rate and nutrient transportation remarkably during chronic food
      restriction. The extension of gut absorption may be one possible reason for
      weight regain. But there is little information about the mechanisms that regulate
      intestinal absorption during food restriction. In this study, we show that the
      surface absorptive areas of gut villi may be enlarged in the jejunum of rats
      maintained on a food restriction regimen compared with animals submitted to
      swimming or sedentary behavior. Our findings show that simply reducing the amount
      of food intake results in an increased appetite accompanied with obvious weight
      regain, and suggest that the resulting enlargement of villi surface areas plays a
      key role in the regain of weight reduction. These results bolster accumulating
      evidence that gut absorption may be a substantial mechanism for resistance of
      weight loss and enhancing the weight regain process.

PMID- 22956622
TI  - Papaya epicarp extract protects against aluminum-induced neurotoxicity.
AB  - In a previous study, we demonstrated the ability of papaya epicarp extract (PEE)
      to protect against oxidative stress-induced insult in human SH-SY5Y neuronal
      cells in a mechanism that appeared to be by means of PEE potent antioxidant
      properties. To further understand this relationship, we examined the effect of
      PEE intervention on aluminum (Al)-induced cytotoxicity in SH-SY5Y cells. The
      results indicated that PEE was effective in protecting against Al-induced cell
      death in a dose-dependent manner. PEE restored the Al-induced inhibition of
      folate-dependent methionine synthase activity and the antioxidant enzymes
      (catalase, glutathione peroxidases and superoxide dismutase). PEE ameliorated the
      Al-induced impairment of intracellular glutathione and total antioxidant
      capacity. Together, these findings indicate that PEE supplementation can play a
      neuroprotective role in ameliorating the changes in redox status of SH-SY5Y cells
      exposed to Al, a well-known environmental toxin that is involved in the
      pathogenesis of neurodegenerative diseases and neurodevelopmental disorders.

PMID- 22956620
TI  - Gene expression in human accessory lacrimal glands of Wolfring.
AB  - PURPOSE: The accessory lacrimal glands are assumed to contribute to the
      production of tear fluid, but little is known about their function. The goal of
      this study was to conduct an analysis of gene expression by glands of Wolfring
      that would provide a more complete picture of the function of these glands.
      METHODS: Glands of Wolfring were isolated from frozen sections of human eyelids
      by laser microdissection. RNA was extracted from the cells and hybridized to gene
      expression arrays. The expression of several of the major genes was confirmed by
      immunohistochemistry. RESULTS: Of the 24 most highly expressed genes, 9 were of
      direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear
      lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to
      protein synthesis, targeting, and secretion, and a large number of genes for
      proteins with antimicrobial activity were detected. Ion channels and
      transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes
      for control of lacrimal function, including cholinergic, adrenergic, vasoactive
      intestinal polypeptide, purinergic, androgen, and prolactin receptors were also
      expressed in gland of Wolfring. CONCLUSIONS: The data suggest that the function
      of glands of Wolfring is similar to that of main lacrimal glands and are
      consistent with secretion electrolytes, fluid, and protein under nervous and
      hormonal control. Since these glands secrete directly onto the ocular surface,
      their location may allow rapid response to exogenous stimuli and makes them
      readily accessible to topical drugs.

PMID- 22956623
TI  - MicroRNA hsa-let-7g targets lectin-like oxidized low-density lipoprotein receptor
      1 expression and inhibits apoptosis in human smooth muscle cells.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been
      identified as a major receptor for oxidatively modified low density lipoprotein
      (ox-LDL) in endothelial cells and smooth muscle cells (SMCs). MicroRNAs are small
      non-coding RNAs that regulate gene expression. Very few studies have reported
      regulation of LOX-1 expression by microRNAs in SMCs. The present study
      demonstrates that the microRNA hsa-let-7g can inhibit LOX-1 expression in a time-
      and dose-dependent fashion, and subsequently inhibit ox-LDL uptake in and
      proliferation of human aortic SMCs. We also show that hsa-let-7g can reduce SMC
      apoptosis by down-regulation of cytochrome c and Smac/Diablo and upregulation of
      Bcl-xL and Bcl-2 expression. Furthermore, we show that hsa-let-7g reduces ox-LDL
      induced increase in the expression of NADPH oxidase (p22(phox) and p47(phox)
      subunits) and subsequent intracellular reactive oxygen species generation,
      phosphorylation of p44/42 mitogen-activated protein kinase and nuclear factor
      kappaB p65 expression. These observations suggest that hsa-let-7g is a critical
      regulator of SMC apoptosis, and may be suitable for therapeutic intervention in
      disease states characterized by LOX-1 over-expression.

PMID- 22956624
TI  - Genetic background determines inflammatory angiogenesis response to dipyridamole
      in mice.
AB  - Inflammation and angiogenesis, key components of fibrovascular tissue growth,
      exhibit considerable variability among species and strains. We investigated
      whether the response of inbred and outbred mice strains to dipyridamole (DP) on
      these processes would present similar variability. The effects of the drug on
      blood vessel formation, inflammatory cell recruitment, collagen deposition and
      cytokine production were determined on the fibroproliferative tissue induced by
      sponge implants in Swiss and Balb/c mice. Angiogenesis as assessed by hemoglobin
      (Hb) and vascular endothelial growth factor (VEGF) concentrations differed
      between the strains. Swiss implants had the highest Hb content but the lowest
      VEGF concentrations. Systemic DP treatment exerted an antiangiogenic effect on
      Balb/c implants but an proangiogenic effect on Swiss implants. The inflammatory
      enzyme activities myeloperoxidase (six-fold higher in Balb/c implants) and N
      acetyl-beta-D-glucosaminidase were reduced by the treatment in Balb/c implants
      only. Nitrite concentrations were also higher in Balb/c implants by 40% after DP
      treatment. Tumor necrosis factor-alpha levels were similar in the implants of
      both strains and were not reduced by DP. Transforming growth factor beta-1 levels
      and collagen deposition also varied between the strains. The inbred strain had
      similar levels of the cytokine but implants of Swiss mice presented more
      collagen. DP treatment reduced collagen deposition in Balb/c implants only. Our
      data showing the influence of the genetic background on marked heterogeneity of
      inflammatory angiogenesis components and differential sensitivity to DP may
      provide some answers to clinical evidence for resistance to angiogenic therapy.

PMID- 22956625
TI  - Enhancer of zeste homolog 2 is overexpressed and contributes to epigenetic
      inactivation of p21 and phosphatase and tensin homolog in B-cell acute
      lymphoblastic leukemia.
AB  - Enhancer of zeste homolog 2 (EZH2) is crucially involved in epigenetic silencing
      by acting as a histone methyltransferase. Although EZH2 is overexpressed in many
      solid cancers, the role of EZH2 in B-cell acute lymphoblastic leukemia (B-ALL)
      remains largely unexplored. In a microarray experiment, we found that EZH2 was
      significantly upregulated in Nalm-6 cells and this was associated with the
      silencing of tumor suppressor genes p21, p53 and phosphatase and tensin homolog
      (PTEN). The abnormal expression of these genes was further confirmed by
      quantitative realtime polymerase chain reaction and Western blot analysis on Nalm
      6 cells. Chromatin immunoprecipitation assay showed that EZH2 and H3K27me3 were
      both enriched in the promoter region of PTEN and p21 in Nalm-6 cells but not in
      normal B cells. Functional analysis showed that siRNA-mediated EZH2 knockdown led
      to decreased proliferation and increased apoptosis of Nalm-6 cells, accompanied
      by the reactivation of PTEN and p21 expression. Furthermore, we found that EZH2
      inhibitor deazaneplanocin A promoted vincristine sulfate-induced apoptosis of
      Nalm-6 cells. Taken together, our data suggest that EZH2 is overexpressed in B
      ALL and promotes the progression of B-ALL by directly mediating the inactivation
      of tumor suppressor genes p21 and PTEN, and could serve as a potential epigenetic
      target for B-ALL therapy.

PMID- 22956626
TI  - Liquid detergent capsule ingestion in children: an increasing trend.

PMID- 22956627
TI  - Loss of A(1) adenosine receptor attenuates alpha-naphthylisothiocyanate-induced
      cholestatic liver injury in mice.
AB  - Cholestasis has limited therapeutic options and is associated with high morbidity
      and mortality. The A(1) adenosine receptor (A(1)AR) was postulated to participate
      in the pathogenesis of hepatic fibrosis induced by experimental extrahepatic
      cholestasis; however, the contribution of A(1)AR to intrahepatic cholestatic
      liver injury remains unknown. Here, we found that mice lacking A(1)AR were
      resistant to alpha-naphthyl isothiocyanate (ANIT)-induced liver injury, as
      evidenced by lower serum liver enzyme levels and reduced extent of histological
      necrosis. Bile acid accumulation in liver and serum was markedly diminished in
      A(1)AR(-/-) mice compared with wild-type (WT) mice. However, biliary and urinary
      outputs of bile acids were significantly enhanced in A(1)AR(-/-) mice. In the
      liver, mRNA expression of genes related to bile acid transport (Bsep and Mdr2)
      and hydroxylation (Cyp3a11) was increased in A(1)AR(-/-) mice. In the kidney,
      A(1)AR deficiency prevented the decrease of glomerular filtration rate caused by
      ANIT. Treatment of WT mice with A(1)AR antagonist DPCPX also protected against
      ANIT hepatotoxicity. Our results indicated that lack of A(1)AR gene protects mice
      from ANIT-induced cholestasis by enhancing toxic biliary constituents efflux
      through biliary excretory route and renal elimination system and suggested a
      potential role of A(1)AR as therapeutic target for the treatment of intrahepatic
      cholestasis.

PMID- 22956628
TI  - Delayed temporal increase of hepatic Hsp70 in ApoE knockout mice after prenatal
      arsenic exposure.
AB  - Prenatal arsenic exposure accelerates atherosclerosis in ApoE(-/-) mice by
      unknown mechanism. Arsenic is a hepatotoxicant, and liver disease increases
      atherosclerosis risk. Prenatal arsenic exposure may predispose to liver disease
      by priming for susceptibility to other environmental insults. Earlier microarray
      analyses showed prenatal arsenic exposure increased Hsc70 (HspA8) and Hsp70
      (HspA1a) mRNAs in livers of 10-week-old mice. We determined effects of prenatal
      arsenic exposure on hepatic Hsp70 and Hsc70 expression by Western blot and on DNA
      methylation by methyl acceptance assay during prenatal and postnatal development.
      Pregnant ApoE(-/-) mice were given drinking water containing 85 mg/l NaAsO(2) (49
      ppm arsenic) from gestation day (GD) 8 to 18. Hsp70 and Hsc70 expression and DNA
      methylation were determined in GD18 fetuses and 3-, 10-, and 24-week-old mice.
      Hsc70 expression was unchanged at all ages. Hsp70 induction was observed at 3 and
      10 weeks, but was unchanged in GD18 fetuses and 24-week livers of mice. Global
      DNA methylation increased with age; arsenic had no effects. Bisulfite sequencing
      of DNA from livers of 10-week-old mice showed Hsp70 promoter region methylation
      was unchanged, but methylation was increased within the transcribed region. Hsf1
      and Nrf2 nuclear translocation were investigated as potential mechanisms of Hsp70
      induction and found unaltered. Putative binding sites were identified in HSP70
      for in utero arsenic exposure-suppressed microRNAs suggesting a possible
      mechanism. Thus, prenatal arsenic exposure causes delayed temporal hepatic Hsp70
      induction, suggesting a transient state of stress in livers which can predispose
      the mice to developing liver disease.

PMID- 22956629
TI  - Differential mouse pulmonary dose and time course responses to titanium dioxide
      nanospheres and nanobelts.
AB  - Three anatase titanium dioxide (TiO(2)) nanoparticles (NPs) were prepared;
      nanospheres (NSs), short nanobelts (NB1), and long nanobelts (NB2). These NPs
      were used to investigate the effect of NP shape and length on lung toxicity. Mice
      were exposed (0-30 ug per mouse) by pharyngeal aspiration and pulmonary toxicity
      was assessed over a 112-day time course. Whole lung lavage data indicated that
      NB1- and NB2-exposed mice, but not NS-exposed mice, had significant dose- and
      time-dependent pulmonary inflammation and damage. Histopathological analyses at
      112 days postexposure determined no interstitial fibrosis in any NS-exposed mice,
      an increased incidence in 30 ug NB1-exposed mice, and significant interstitial
      fibrosis in 30 ug NB2-exposed mice. At 112 days postexposure, lung burden of NS
      was decreased by 96.4% and NB2 by 80.5% from initial deposition levels. At 112
      days postexposure, enhanced dark field microscopy determined that alveolar macro-
      phages were the dominant deposition site, but a fraction of NB1 and NB2 was
      observed in the alveolar interstitial spaces. For the 30 ug exposure groups at
      112 days postexposure, confocal micro- scopy and immunofluorescent staining
      demonstrated that retained NB2 but not NS were present in the interstitium
      subjacent to the terminal bronchiole near the normal location of the smallest
      lymphatic capillaries in the lung. These lymphatic capillaries play a critical
      role in particle clearance, and the accumulation of NB2, but not NS, suggests
      possible impaired lymphatic clearance by the high aspect ratio particles. In
      summary, our data indicate that TiO(2) NP shape alters pulmonary responses, with
      severity of responses being ranked as NS < NB1 < NB2.

PMID- 22956631
TI  - PPTOX III: environmental stressors in the developmental origins of disease-
      evidence and mechanisms.
AB  - Fetal and early postnatal development constitutes the most vulnerable time period
      of human life in regard to adverse effects of environmental hazards. Subtle
      effects during development can lead to functional deficits and increased disease
      risk later in life. The hypothesis stating that environmental exposures leads to
      altered programming and, thereby, to increased susceptibility to disease or
      dysfunction later in life has garnered much support from both experimental and
      epidemiological studies. Similar observations have been made on the long-term
      impact of nutritional unbalance during early development. In an effort to bridge
      the fields of nutritional and environmental developmental toxicity, the Society
      of Toxicology sponsored this work. This report summarizes novel findings in
      developmental toxicity as reported by select invited experts and meeting
      attendees. Recommendations for the application and improvement of current and
      future research efforts are also presented.

PMID- 22956632
TI  - Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-alpha
      pharmacology.
AB  - Inhibitor-of-apoptosis (IAP) proteins suppress apoptosis and are overexpressed in
      a variety of cancers. Small-molecule IAP antagonists are currently being tested
      in clinical trials as novel cancer therapeutics. GDC-0152 is a small-molecule
      drug that triggers tumor cell apoptosis by selectively antagonizing IAPs. GDC
      0152 induces NF-kappaB transcriptional activity leading to expression of several
      chemokines and cytokines, of which tumor necrosis factor alpha (TNF-alpha) is the
      most important for single-agent tumor activity. TNF-alpha is a pleiotropic
      cytokine that drives a variety of cellular responses, comprising inflammation,
      proliferation, and cell survival or death depending on the cellular context. As
      malignant and normal cells produce TNF-alpha upon IAP antagonism, increased TNF
      alpha could drive both efficacy and toxicity. The toxicity profile of GDC-0152 in
      dogs and rats was characterized after iv dose administration once every 2 weeks
      for four doses. Findings in both species consisted of a dose-related, acute,
      systemic inflammatory response, and hepatic injury. Laboratory findings included
      elevated plasma cytokines, an inflammatory leukogram, and increased liver
      transaminases with histopathological findings of inflammatory infiltrates and
      apoptosis/necrosis in multiple tissues; a toxicology profile consistent with TNF
      alpha-mediated toxicity. Dogs exhibited more severe findings than rats, and
      humans did not exhibit these findings, at comparable exposures across species.
      Furthermore, elevations in blood neutrophil count, serum monocyte chemoattractant
      protein-1, and other markers of inflammation corresponded to GDC-0152 exposure
      and toxicity and thus may have utility as safety biomarkers.

PMID- 22956630
TI  - Effects of parabens on adipocyte differentiation.
AB  - Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include
      methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben.
      Paraben esters and their salts are widely used as preservatives in cosmetics,
      toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the
      use of such products from dermal contact, ingestion, and inhalation. However,
      research on the effects of parabens on health is limited, and the effects of
      parabens on adipogenesis have not been systematically studied. Here, we report
      that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine
      3T3-L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA
      expression of adipocyte-specific markers; (2) the adipogenic potency of parabens
      is increased with increasing length of the linear alkyl chain in the following
      potency ranking order: methyl- < ethyl- < propyl- < butylparaben. The extension
      of the linear alkyl chain with an aromatic ring in benzylparaben further augments
      the adipogenic ability, whereas 4-hydroxybenzoic acid, the common metabolite of
      all parabens, and the structurally related benzoic acid (without the OH group)
      are inactive in promoting 3T3-L1 adipocyte differentiation; (3) parabens activate
      glucocorticoid receptor and/or peroxisome proliferator-activated receptor gamma
      in 3T3-L1 preadipocytes; however, no direct binding to, or modulation of, the
      ligand binding domain of the glucocorticoid receptor by parabens was detected by
      glucocorticoid receptor competitor assays; and lastly, (4) parabens, butyl- and
      benzylparaben in particular, also promote adipose conversion of human adipose
      derived multipotent stromal cells. Our results suggest that parabens may
      contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo
      needs to be examined further.

PMID- 22956633
TI  - Telephone-delivered health coaching improves anxiety outcomes after myocardial
      infarction: the 'ProActive Heart' trial.
AB  - BACKGROUND: Recently, we found a telephone-delivered secondary prevention
      programme using health coaching ('ProActive Heart') to be effective in improving
      a range of key behavioural outcomes for myocardial infarction (MI) patients. What
      remains unclear, however, is the extent to which these treatment effects
      translate to important psychological outcomes such as depression and anxiety
      outcomes, an issue of clinical significance due to the substantial proportion of
      MI patients who experience depression and anxiety. The objective of the study was
      to investigate, as a secondary hypothesis of a larger trial, the effects of a
      telephone-delivered health coaching programme on depression and anxiety outcomes
      of MI patients. DESIGN: Two-arm, parallel-group, randomized, controlled design
      with six-months outcomes. METHODS: Patients admitted to one of two tertiary
      hospitals in Brisbane, Australia following MI were assessed for eligibility. Four
      hundred and thirty patients were recruited and randomly assigned to usual care or
      an intervention group comprising up to 10 telephone-delivered 'health coaching'
      sessions (ProActive Heart). Regression analysis compared Hospital Anxiety and
      Depression Scale scores of completing participants at six months (intervention: n
      = 141 versus usual care: n = 156). RESULTS: The intervention yielded reductions
      in anxiety at follow-up (mean difference = -0.7, 95% confidence interval=-1.4,
      0.02) compared with usual care. A similar pattern was observed in mean depression
      scores but was not statistically significant. CONCLUSIONS: The ProActive Heart
      programme effectively improves anxiety outcomes of patients following myocardial
      infarction. If combined with psychological-specific treatment, this programme
      could impact anxiety of greater intensity in a clinically meaningful way.

PMID- 22956634
TI  - Hunt's team at the Department of Health includes doctor who left BMA over strike.

PMID- 22956635
TI  - Texas records worst outbreak of West Nile virus on record.

PMID- 22956636
TI  - Organ matching website says it will operate within the law.

PMID- 22956637
TI  - Treatment of symptomatic bullous keratopathy with poor visual prognosis using a
      modified Gundersen conjunctival flap and amniotic membrane.
AB  - A modified Gundersen conjunctival flap combined with amniotic membrane to treat
      symptomatic bullous keratopathy and poor visual prognosis is described. A 360
      degrees  conjunctival peritomy was performed 2 mm from the limbus. After complete
      epithelial removal of the corneo-conjunctival surface, an amniotic membrane graft
      was sutured at the peripheral cornea with a running 10-0 nylon suture. Single 9-0
      polyglactin sutures attached the edges of the amniotic membrane with the
      peritomized conjunctiva, which lay over the amniotic membrane. Five eyes were
      treated. Epithelialization, resolution of the pain, presence of ocular surface
      inflammation, and reinterventions were assessed. All eyes showed immediate
      resolution of the pain and minimal inflammation. In 1 eye, the amniotic membrane
      was reabsorbed before complete epithelialization. No reinterventions were
      required. All eyes were asymptomatic for at least 16 months. This technique
      provided sustained relief of symptomatic bullous keratopathy while significantly
      reducing the conjunctival manipulation and the anatomical distortion associated
      with classic sliding conjunctival flaps.

PMID- 22956638
TI  - Reverse optic capture of the single-piece acrylic intraocular lens in eyes with
      posterior capsule rupture.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the clinical results of reverse optic
      capture (ROC) with single-piece posterior chamber intraocular lenses (PC-IOLs) in
      cases of phacoemulsification cataract and IOL surgery with posterior capsular
      rupture. PATIENTS AND METHODS: Preoperative diagnosis, intraoperative events,
      surgical parameters, intraoperative and postoperative complications, and
      preoperative and postoperative visual acuity and refraction of 16 eyes that
      underwent ROC were reviewed and analyzed. The fellow eye of 12 patients
      undergoing uneventful phacoemulsification without optic capture served as the
      control group. RESULTS: Over a mean of 19 months' follow-up, 94% of eyes in the
      ROC group and 92% in the control group achieved a best-corrected visual acuity of
      20/25 or better. Ninety-four percent of eyes in the ROC group and 100% in the
      control group had postoperative spherical equivalent +/- 1.00 D of the intended
      refraction. Refraction was stable between 1 month and final follow-up in both
      groups. In all eyes with ROC, the IOL remained well centered with a securely
      captured optic. There were no vision-threatening complications throughout the
      follow-up. CONCLUSION: The comparable outcomes in both groups suggests that optic
      capture of a single-piece acrylic IOL through an anterior capsulorhexis merits
      consideration for IOL placement in selected cases of insufficient posterior
      capsule support.

PMID- 22956640
TI  - The PONS study and its place in the strategy of health gain in Poland.
AB  - After 30 years (1960-1990) of adult health decline, since the beginning of the
      political and economic transformation in the early 1990s.a dramatic reversal of
      health trends is being observed in Poland, In contrast, in the countries of
      Western Europe, a significant, steady health gain has been observed already since
      the end of World War II. At the beginning of the 21 st  century one in three men
      in Poland still do not reach the age of 65, which dramatically contrasts with the
      one-digit premature mortality in Western Europe (EU15). In Poland very high
      proportion of this mortality (men ~30%, women ~15%) occur in working age
      population hampering social and economic development. Non-communicable diseases
      and risk factors (smoking, drinking, obesity) are major cause of heath inequality
      and contribute to poverty. This health gap, leading to an over-proportional loss
      of human capital in Eastern Europe, is one of the most crucial challenges for the
      European Union during the period of economic crisis.

PMID- 22956639
TI  - Regulatory RNAs in the light of Drosophila genomics.
AB  - Many aspects of gene regulation are mediated by RNA molecules. However,
      regulatory RNAs have remained elusive until very recently. At least three types
      of small regulatory RNAs have been characterized in Drosophila: microRNAs
      (miRNAs), piwi-interacting RNAs and endogenous siRNAs. A fourth class of
      regulatory RNAs includes known long non-coding RNAs such as roX1 or bxd. The
      initial sequencing of the Drosophila melanogaster genome has served as a scaffold
      to study the transcriptional profile of an animal, revealing the complexities of
      the function and biogenesis of regulatory RNAs. The comparative analysis of 12
      Drosophila genomes has been crucial for the study of microRNA evolution. However,
      comparative genomics of other RNA regulators is confounded by technical problems:
      genomic loci are poorly conserved and frequently encoded in the heterochromatin.
      Future developments in genome sequencing and population genomics in Drosophila
      will continue to shed light on the conservation, evolution and function of
      regulatory RNAs.

PMID- 22956642
TI  - Meta-analysis of the association between obstructive sleep apnoea and
      postoperative outcome.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) is often undiagnosed before elective
      surgery and may predispose patients to perioperative complications. METHODS: A
      literature search of PubMed-Medline, Web of Science, Scopus, EMBASE, Cochrane
      Database of Systematic Reviews, and Cochrane Central Register of Controlled
      Trials up to November 2010 was conducted. Our search was restricted to cohort or
      case-control studies in adults diagnosed with OSA by screening questionnaire,
      oximetry, or polysomnography. Studies without controls, involving upper airway
      surgery, and with OSA diagnosed by ICD-9 codes alone were excluded. The primary
      postoperative outcomes were desaturation, acute respiratory failure (ARF),
      reintubation, myocardial infarction/ischaemia, arrhythmias, cardiac arrest,
      intensive care unit (ICU) transfer, and length of stay. RESULTS: Thirteen studies
      were included in the final analysis (n=3942). OSA was associated with
      significantly higher odds of any postoperative cardiac events [45/1195 (3.76%) vs
      24/1420 (1.69%); odds ratio (OR) 2.07; 95% confidence interval (CI) 1.23-3.50,
      P=0.007] and ARF [33/1680 (1.96%) vs 24/3421 (0.70%); OR 2.43, 95% CI 1.34-4.39,
      P=0.003]. Effects were not heterogeneous for these outcomes (I(2)=0-15%, P>0.3).
      OSA was also significantly associated with higher odds of desaturation [189/1764
      (10.71%) vs 105/1881 (5.58%); OR 2.27, 95% CI 1.20-4.26, P=0.01] and ICU transfer
      [105/2062 (5.09%) vs 58/3681 (1.57%), respectively; OR 2.81, 95% CI 1.46-5.43,
      P=0.002]. Both outcomes showed a significant degree of heterogeneity of the
      effect among studies (I(2)=57-68%, P<0.02). Subgroup analyses had similar
      conclusions as main analyses. CONCLUSIONS: The incidence of postoperative
      desaturation, respiratory failure, postoperative cardiac events, and ICU
      transfers was higher in patients with OSA.

PMID- 22956641
TI  - Promotion of couples' voluntary HIV counselling and testing in Lusaka, Zambia by
      influence network leaders and agents.
AB  - OBJECTIVES: Hypothesising that couples' voluntary counselling and testing (CVCT)
      promotions can increase CVCT uptake, this study identified predictors of
      successful CVCT promotion in Lusaka, Zambia. DESIGN: Cohort study. SETTING:
      Lusaka, Zambia. PARTICIPANTS: 68 influential network leaders (INLs) identified
      320 agents (INAs) who delivered 29 119 CVCT invitations to heterosexual couples.
      INTERVENTION: The CVCT promotional model used INLs who identified INAs, who in
      turn conducted community-based promotion and distribution of CVCT invitations in
      two neighbourhoods over 18 months, with a mobile unit in one neighbourhood
      crossing over to the other mid-way through. PRIMARY OUTCOME: The primary outcome
      of interest was couple testing (yes/no) after receipt of a CVCT invitation. INA,
      couple and invitation characteristics predictive of couples' testing were
      evaluated accounting for two-level clustering. RESULTS: INAs delivered
      invitations resulting in 1727 couples testing (6% success rate). In multivariate
      analyses, INA characteristics significantly predictive of CVCT uptake included
      promoting in community-based (adjusted OR (aOR)=1.3; 95% CI 1.0 to 1.8) or health
      (aOR=1.5; 95% CI 1.2 to 2.0) networks versus private networks; being employed in
      the sales/service industry (aOR=1.5; 95% CI 1.0 to 2.1) versus unskilled manual
      labour; owning a home (aOR=0.7; 95% CI 0.6 to 0.9) versus not; and having tested
      for HIV with a partner (aOR=1.4; 95% CI 1.1 to 1.7) or alone (aOR=1.3; 95% CI 1.0
      to 1.6) versus never having tested. Cohabiting couples were more likely to test
      (aOR=1.4; 95% CI 1.2 to 1.6) than non-cohabiting couples. Context characteristics
      predictive of CVCT uptake included inviting couples (aOR=1.2; 95% CI 1.0 to 1.4)
      versus individuals; the woman (aOR=1.6; 95% CI 1.2 to 2.2) or couple (aOR=1.4;
      95% CI 1.0 to 1.8) initiating contact versus the INA; the couple being socially
      acquainted with the INA (aOR=1.6; 95% CI 1.4 to 1.9) versus having just met; home
      invitation delivery (aOR=1.3; 95% CI 1.1 to 1.5) versus elsewhere; and easy
      invitation delivery (aOR=1.8; 95% CI 1.4 to 2.2) versus difficult as reported by
      the INA. CONCLUSIONS: This study demonstrated the ability of influential people
      to promote CVCT and identified agent, couple and context-level factors associated
      with CVCT uptake in Lusaka, Zambia. We encourage the development of CVCT
      promotions in other sub-Saharan African countries to support sustained CVCT
      dissemination.

PMID- 22956643
TI  - i-gelTM supraglottic airway in clinical practice: a prospective observational
      multicentre study.
AB  - BACKGROUND: The i-gelTM supraglottic airway device has been studied in randomized
      controlled studies, but it has not been evaluated in a large prospective patient
      cohort. Therefore, we performed this prospective multicentre observational study
      to evaluate success rates, airway leak pressure, risk factors for i-gel failure,
      and adverse events. METHODS: With Ethics Committee approval and waiver of
      patients' consent, data about anaesthesia providers, patient characteristics, and
      the performance of the i-gel were recorded in five independent hospitals in
      Switzerland over a period of 24 months. We analysed success rates, leak
      pressures, adverse events, and risk factors for failure. RESULTS: Data from 2049
      i-gel uses were analysed. Patients' mean age was 47 (range 6-91) yr. The primary
      i-gel success rate without changing size was 93%; the overall success rate was
      96%. Insertion was deemed very easy or easy in 92%. The mean airway leak pressure
      was 26 (8) cm H(2)O. The mean anaesthesia time was 67 (42) min. Risk factors
      associated with i-gel failure were males (P<0.001), impaired mandibular
      subluxation (P=0.01), poor dentition (P=0.02), and older age (P<0.01). Adverse
      events recorded were laryngeal spasms (n=25, 1.2%), blood stained airway devices
      (n=79, 3.9%), transient nerve damage (n=2, 0.1%), one case of transient vasovagal
      asystole, and one glottic haematoma. CONCLUSIONS: The i-gel is a reliable
      supraglottic airway device failing in <5% and providing high airway leak
      pressures. Males, impaired mandibular subluxation, poor dentition, and older age
      are risk factors associated with primary device failure. Serious adverse events
      are rare.

PMID- 22956645
TI  - Investigating neuroplastic changes in the human brain induced by transcranial
      direct (tDCS) and alternating current (tACS) stimulation methods.

PMID- 22956644
TI  - HER2 amplification: a potential mechanism of acquired resistance to EGFR
      inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M
      mutation.
AB  - EGF receptor (EGFR)-mutant lung cancers eventually become resistant to treatment
      with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib
      and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models
      and human patients. Because afatinib is also a potent HER2 inhibitor, we
      investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and in
      vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation.
      HER2 overexpression or knockdown confers resistance or sensitivity, respectively,
      in all studied cell line models. FISH analysis revealed that HER2 was amplified
      in 12% of tumors with acquired resistance versus only 1% of untreated lung
      adenocarcinomas. Notably, HER2 amplification and EGFR(T790M) were mutually
      exclusive. Collectively, these results reveal a previously unrecognized mechanism
      of resistance to EGFR-TKIs and provide a rationale to assess the status and
      possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs.

PMID- 22956646
TI  - Computational models of transcranial direct current stimulation.
AB  - During transcranial direct current stimulation (tDCS), controllable dose
      parameters are electrode number (typically 1 anode and 1 cathode), position,
      size, shape, and applied electric current. Because different electrode montages
      result in distinct brain current flow patterns across the brain, tDCS dose
      parameters can be adjusted, in an application-specific manner, to target or avoid
      specific brain regions. Though the tDCS electrode montage often follows basic
      rules of thumb (increased/decreased excitability "under" the anode/cathode
      electrode), computational forward models of brain current flow provide more
      accurate insight into detailed current flow patterns and, in some cases, can even
      challenge simplified electrode-placement assumptions. With the increased
      recognized value of computational forward models in informing tDCS montage design
      and interpretation of results, there have been recent advances in modeling tools
      and a greater proliferation of publications.  In addition, the importance of
      customizing tDCS for potentially vulnerable populations (eg, skull defects, brain
      damage/stroke, and extremes of age) can be considered. Finally, computational
      models can be used to design new electrode montages, for example, to improve
      spatial targeting such as high-definition tDCS. Pending further validation and
      dissemination of modeling tools, computational forward models of neuromodulation
      will become standard tools to guide the optimization of clinical trials and
      electrotherapy.

PMID- 22956647
TI  - Effects of transcranial electrical stimulation on cognition.
AB  - Alterations of cortical excitability, oscillatory as well as non-oscillatory, are
      physiological derivates of cognitive processes, such as perception, working
      memory, learning, and long-term memory formation. Since noninvasive electrical
      brain stimulation is capable of inducing alterations in the human brain, these
      stimulation approaches might be attractive tools to modulate cognition.
      Transcranial direct current stimulation (tDCS) alters spontaneous cortical
      activity, while transcranial alternating current stimulation (tACS) and
      transcranial random noise stimulation (tRNS) are presumed to induce or interfere
      with oscillations of cortical networks. Via these mechanisms, the respective
      stimulation techniques have indeed been shown to modulate cognitive processes in
      a multitude of studies conducted during the last years. In this review, we will
      gather knowledge about the potential of noninvasive electrical brain stimulation
      to study and modify cognitive processes in healthy humans and discuss directions
      of future research.

PMID- 22956648
TI  - Functional neuroimaging and transcranial electrical stimulation.
AB  - Transcranial electrical stimulation (tES) is a noninvasive tool for inducing
      local and widespread neuroplastic changes in brain networks. The combination of
      tES with various neuroimaging techniques provides whole brain data on the working
      mechanisms of tES, in particular on the development of large-scale activation
      patterns of interconnected neuronal regions induced by tES. This review focuses
      on the combined usage of a noninvasive application of transcranial direct current
      stimulation and functional magnetic resonance imaging and on magnetic resonance
      spectroscopy.

PMID- 22956650
TI  - Raising the stakes for acute deep vein thrombosis care: understanding the
      catheter-directed venous thrombolysis study.

PMID- 22956651
TI  - Diagnostic tests (1) - sensitivity and specificity.

PMID- 22956652
TI  - Reversible pH-responsive fluorescence of water-soluble polyfluorenes and their
      application in metal ion detection.
AB  - A novel water-soluble conjugated polymer poly{(4,4'-azobenzene)-2,7-[9,9-bis(6'
      N,N,N,-trimethylammonium)hexyl fluorene]dibromide} (PFAB) has been designed and
      synthesized via Suzuki cross-coupling the fluorene units and azobenzene units.
      Through simple photoreduction, the azo group of the nonfluorescent PFAB to
      hydrazine group using UV light, polyfluorene PFAB-L with turn-on fluorescence in
      aqueous solution is obtained. The optical measurements illustrate that the
      generation of the flexible hydrazine group induces face-to-face arrangement of
      phenyl-fluorene-phenyl moieties. Therefore, the excimer formation of phenyl
      fluorene-phenyl moieties was induced in PFAB-L. And the fluorescence of PFAB-L
      can be controlled through modulating the protonation of the -NH-NH- group in
      solution with different pH. The pH-responsive property is reversible. Moreover,
      the Fe(3+) ions can selectively quench the fluorescence of the PFAB-L. This new
      polymer PFAB-L could be used for selective and sensitive sensing Fe(3+) ions in
      aqueous solution.

PMID- 22956653
TI  - Effect of thickness-dependent microstructure on the out-of-plane hole mobility in
      poly(3-hexylthiophene) films.
AB  - Regioregular poly(3-hexylthiophene) (RR-P3HT) is a widely used donor material for
      bulk heterojunction polymer solar cells. While much is known about the structure
      and properties of RR-P3HT films, important questions regarding hole mobilities in
      this material remain unresolved. Measurements of the out-of-plane hole
      mobilities, MU, of RR-P3HT films have been restricted to films in the thickness
      regime on the order of micrometers, beyond that generally used in solar cells,
      where the film thicknesses are typically 100 to 200 nm. Studies of in-plane
      carrier mobilities have been conducted in thinner films, in the thickness range
      100-200 nm. However, the in-plane and out-of-plane hole mobilities in RR-P3HT can
      be significantly different. We show here that the out-of-plane hole mobilities in
      neat RR-P3HT films increase by an order of magnitude, from 10(-4) cm(2)/V.s, for
      a 80 nm thick film, to a value of 10(-3) cm(2)/V.s for films thicker than 700 nm.
      Through a combination of morphological characterization and simulations, we show
      that the thickness dependent mobilities are not only associated with the
      differences between the average morphologies of thick films and thin films, but
      specifically associated with changes in the local morphology of films as a
      function of distance from the interfaces.

PMID- 22956654
TI  - Antibody responses to individual Bordetella pertussis fimbrial antigen Fim2 or
      Fim3 following immunization with the five-component acellular pertussis vaccine
      or to pertussis disease.
AB  - Bordetella pertussis expresses two serologically distinct fimbriae (Fim2 and
      Fim3) which are included in the Sanofi Pasteur 5-component acellular pertussis
      vaccine, and antibody responses to these antigens have been shown to be
      associated with protection. Studies to date have assessed the IgG response to
      this vaccine using a copurified mixture of Fim2 and Fim3, and the response to the
      individual antigens has not been characterized. We have purified separate Fim2
      and Fim3 from strains that express either Fim2 or Fim3 and have used these
      antigens in an enzyme-linked immunosorbent assay (ELISA) to quantify IgG
      responses following immunization with 5-component acellular pertussis vaccine in
      15-month-old, 4- to 6-year-old, and 11- to 18-year-old subjects. All individuals
      showed increases in Fim2 and Fim3 IgG concentrations following immunization, with
      3-fold-greater Fim2 than Fim3 IgG concentrations seen in the younger two age
      groups. Fim2 IgG concentrations were 1.5-fold greater than Fim3 IgG
      concentrations in the 11- to 18-year-olds. We have also compared Fim2 and Fim3
      IgG concentrations in individuals with prolonged cough who were diagnosed as
      having recent pertussis using a pertussis toxin (Ptx) IgG ELISA with individuals
      with prolonged cough but without elevated Ptx IgG concentrations. Individuals
      with evidence of recent pertussis had greater Fim3 IgG concentrations, consistent
      with the predominant serotype of isolates obtained in the United Kingdom.
      However, a surprising number of individuals had moderate Fim2 IgG concentrations
      despite very few isolates of that serotype obtained in the sampling period.

PMID- 22956655
TI  - Identification of synthetic host defense peptide mimics that exert dual
      antimicrobial and anti-inflammatory activities.
AB  - A group of synthetic antimicrobial oligomers, inspired by naturally occurring
      antimicrobial peptides, were analyzed for the ability to modulate innate immune
      responses to Toll-like receptor (TLR) ligands. These synthetic mimics of
      antimicrobial peptides (SMAMPs) specifically reduced cytokine production in
      response to Staphylococcus aureus and the S. aureus component lipoteichoic acid
      (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor
      necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus
      or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to
      LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP
      greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected
      with S. aureus while simultaneously reducing bacterial loads dramatically (4
      log(10)). Thus, these SMAMPs can eliminate the damage induced by pathogen
      associated molecular patterns (PAMPs) while simultaneously eliminating infection
      in vivo. They are the first known SMAMPs to demonstrate anti-inflammatory and
      antibacterial activities in vivo.

PMID- 22956656
TI  - Influenza virus h5 DNA vaccination is immunogenic by intramuscular and
      intradermal routes in humans.
AB  - Avian influenza virus causes outbreaks in domestic and wild birds around the
      world, and sporadic human infections have been reported. A DNA vaccine encoding
      hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially
      tested in two randomized phase I clinical studies. Vaccine Research Center study
      304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo,
      1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by
      intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to
      evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of
      0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg
      Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n =
      11/group). Injections were administered at weeks 0, 4, and 8 in both studies.
      Antibody responses to H5 were assessed by hemagglutination inhibition (HAI)
      assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and
      the H5 T cell responses were assessed by enzyme-linked immunospot and
      intracellular cytokine staining assays. There were no vaccine-related serious
      adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d.
      vaccination compared to i.m. vaccination induced a greater frequency and
      magnitude of response by ELISA, but there were no significant differences in the
      frequency or magnitude of response between the i.d. and i.m. routes in the HAI or
      neutralization assays. T cell responses were more common in subjects who received
      the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding
      H5 is safe and immunogenic and served to define the proper dose and route for
      further studies. The i.d. injection route did not offer a significant advantage
      over the i.m. route, and no difference was detected by delivery to one site
      versus splitting the dose between two sites for i.d. vaccine administration. The
      4-mg dose (i.m) was further investigated in prime-boost regimens.

PMID- 22956658
TI  - Colorimetric and resistive polymer electrolyte thin films for real-time humidity
      sensors.
AB  - We have developed fast responsive, colorimetric and resistive-type polymeric
      humidity sensors from a series of self-assembled poly(styrenesulfonate
      methylbutylene) (PSS-b-PMB) block copolymers with tailored hygroscopic
      properties. In dry state, the PSS-b-PMB films exhibit hexagonal cylindrical
      morphology where hydrophobic PMB cylinders are dispersed within a PSS matrix.
      Under levels of humidity, the PSS-b-PMB thin films self-displayed discernible
      reflective color changes, covering almost entire visible light regions from
      violet (RH = 20%) to red (RH = 95%). The sensors also revealed a few orders of
      magnitude changes in impedance with exposure to humid air by taking advantages of
      strong polymer electrolytes characteristics. Remarkably, the time to complete the
      changes in the signals was only a few seconds, as rationalized by good
      connectivity of the PSS domains and short water diffusion pathways in nanometer
      scales. Repeated hydration/dehydration tests demonstrated reliable sensor
      properties, which is in sharp contrast to the poor stability of PSS homopolymer
      sensors lacking organization.

PMID- 22956659
TI  - Tailoring properties of cross-linked polyimide aerogels for better moisture
      resistance, flexibility, and strength.
AB  - Combinations of rigid and flexible aromatic diamines were used to tailor the
      properties of octa(aminophenyl)-silsesquioxane (OAPS) cross-linked polyimide
      aerogels. 2,2'-Dimethylbenzidine (DMBZ) or p-phenylenediamine (PPDA) was used in
      combination with the more-flexible diamine, 4,4'-oxydianiline (ODA). The amount
      of rigid diamine was varied from 0% to 100% of the total diamines in the
      backbone. The resulting aerogels vary in density, shrinkage, porosity, surface
      area, mechanical and thermal properties (depending on the type of diamine and the
      proportions of rigid diamine to flexible diamine used). Replacing ODA with PPDA
      increases shrinkage that occurs during gelation and processing, while increasing
      the DMBZ fraction decreases shrinkage. Replacing ODA with 50 mol% of DMBZ
      maintains the flexibility of thin films, while the moisture resistance of the
      aerogels is greatly improved.

PMID- 22956657
TI  - Development of an inhalational Bacillus anthracis exposure therapeutic model in
      cynomolgus macaques.
AB  - Appropriate animal models are required to test medical countermeasures to
      bioterrorist threats. To that end, we characterized a nonhuman primate (NHP)
      inhalational anthrax therapeutic model for use in testing anthrax therapeutic
      medical countermeasures according to the U.S. Food and Drug Administration Animal
      Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of
      Bacillus anthracis Ames spores. Specific diagnostic parameters were detected
      relatively early in disease progression, i.e., by blood culture (~37 h
      postchallenge) and the presence of circulating protective antigen (PA) detected
      by electrochemiluminescence (ECL) ~38 h postchallenge, whereas nonspecific
      clinical signs of disease, i.e., changes in body temperature, hematologic
      parameters (ca. 52 to 66 h), and clinical observations, were delayed. To
      determine whether the presentation of antigenemia (PA in the blood) was an
      appropriate trigger for therapeutic intervention, a monoclonal antibody specific
      for PA was administered to 12 additional animals after the circulating levels of
      PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated
      animals survived compared to 17% of the untreated controls, suggesting that
      intervention at the onset of antigenemia is an appropriate treatment trigger for
      this model. Moreover, the onset of antigenemia correlated with bacteremia, and
      NHPs were treated in a therapeutic manner. Interestingly, brain lesions were
      observed by histopathology in the treated nonsurviving animals, whereas this
      observation was absent from 90% of the nonsurviving untreated animals. Our
      results support the use of the cynomolgus macaque as an appropriate therapeutic
      animal model for assessing the efficacy of medical countermeasures developed
      against anthrax when administered after a confirmation of infection.

PMID- 22956660
TI  - Extraskeletal osteochondroma of the medial arch of the foot.
AB  - Extraskeletal osteochondromas are benign, slow growing, and often painless
      neoplasms. Although they are histologically similar to conventional
      osteochondromas, extraskeletal osteochondromas are not attached to a parent bone.
      When a well-defined osseous mass in the soft tissue without any direct continuity
      with the adjacent bone or joint is encountered, a diagnosis of extraskeletal
      osteochondroma should be strongly considered. It should be identified to avoid
      unnecessary aggressive surgical treatment. We present a patient with symptomatic
      extraskeletal osteochondroma of the medial arch of the foot. It was treated by
      local excision and no evidence of local recurrence clinically or radiographically
      after 51 months of follow-up. LEVELS OF EVIDENCE: Therapeutic, Level IV, Case
      study.

PMID- 22956661
TI  - The impact of foot insole on the energy consumption of flat-footed individuals
      during walking.
AB  - BACKGROUND: The human foot contains one of the most variable structures of the
      body, which is the medial longitudinal arch. Decrease in the height of this arch
      results in a flat foot. Although there is some evidence regarding the influence
      of flat foot on gait performance of flat-footed individuals, there is no strong
      evidence to support the theory that being flat-footed has an effect on energy
      consumption. Therefore, the aim of this study was to find the relationship
      between flat foot and energy consumption. METHOD: Two groups of normal and flat
      footed participants were recruited in this research project. They were selected
      from the staff and students of Isfahan University of Medical Sciences. The foot
      indexes of both groups were obtained using the footprint method with help of
      Solid worker software. The physiological cost index (PCI) of the participants was
      measured by the use of a heart rate monitoring system (Polar Electro, Finland).
      The differences between the PCIs of both groups of participants was determined
      using a t test. In addition, the influence of using an insole was evaluated using
      a paired t test. RESULT: The energy consumption of flat-footed individuals
      differed significantly from that of normal individuals (the PCIs of normal and
      flat-footed individuals were 0.357 and 0.368 beats/m, respectively). Using a foot
      insole improved the performance of the flat-footed individuals during walking.
      CONCLUSION: The PCI of flat-footed individuals is more than that of normal
      participants as a result of misalignment of foot structure. Moreover, using a
      foot insole improved foot alignment and decreased energy consumption.

PMID- 22956662
TI  - An osteochondral lesion in the distal fibula: a case report.
AB  - Osteochondral lesions of the talus are well-recognized clinical entities;
      however, this report illustrates a rare case of an osteochondral defect in the
      distal fibula. A 15-year-old male was referred to the orthopaedic services with a
      9-month history of persistent ankle pain following an initial inversion injury.
      Plain X-ray was unremarkable but magnetic resonance imaging and computed
      tomography revealed an osteochondral lesion at the level of the fibular physeal
      scar. The patient underwent an ankle arthroscopy where an unstable chondral flap
      was debrided and the associated fissure decompressed. The patient made an
      uneventful recovery and returned to normal sporting activities, symptom free.
      This diagnosis should be considered in patients presenting with chronic ankle
      pain particularly with a history of an inversion injury. The purpose of this
      report is to raise awareness of this condition. LEVELS OF EVIDENCE: Therapeutic,
      Level IV, Case study.

PMID- 22956663
TI  - Test-retest reliability of the Win-Track platform in analyzing the gait
      parameters and plantar pressures during barefoot walking in healthy adults.
AB  - The Win-Track platform is an instrument used to measure plantar pressures and
      gait parameters during barefoot walking. The objective of this study was to
      determine the test-retest reliability of the system in assessing plantar
      pressures and temporal gait variables between 1-step and 3-step gait protocols. A
      total of 30 healthy participants (18 women and 12 men; age 23.7 +/- 4.75 years)
      were recruited for the study. The 1-step gait protocol exhibited good reliability
      in terms of single stance, step duration and swing duration of the left foot;
      stride duration of the right foot; stride length; and step length of the right
      foot, with intraclass correlation coefficients (ICCs) ranging from 0.75 to 0.88.
      The 3-step gait protocol showed good reliability, with ICC values ranging between
      0.75 and 0.90 in cadence; step duration of the right foot; double-stance duration
      and swing duration of the right foot; stride length of the right foot; step
      length and gait cycle length of the right and the left foot; and the area covered
      by the first, second, and third foot. The authors concluded that the Win-Track
      platform provided reliable plantar pressures and temporal gait measures, and the
      3-step gait protocol showed better reliability compared with the 1-step gait
      protocol.

PMID- 22956664
TI  - Is it just a brick wall or a sign from the universe? An fMRI study of
      supernatural believers and skeptics.
AB  - We examined with functional magnetic resonance imaging the brain activity of 12
      supernatural believers and 11 skeptics who first imagined themselves in critical
      life situations (e.g. problems in intimate relationships) and then watched
      emotionally charged pictures of lifeless objects and scenery (e.g. two red
      cherries bound together). Supernatural believers reported seeing signs of how the
      situations were going to turn out in the pictures more often than skeptics did.
      Viewing the pictures activated the same brain regions among all participants
      (e.g. the left inferior frontal gyrus, IFG). However, the right IFG, previously
      associated with cognitive inhibition, was activated more strongly in skeptics
      than in supernatural believers, and its activation was negatively correlated to
      sign seeing in both participant groups. We discuss the implications of these
      findings for research on the universal processes that may underlie supernatural
      beliefs and the role of cognitive inhibition in explaining individual differences
      in such beliefs. 

PMID- 22956665
TI  - An ERP study of vocal emotion processing in asymmetric Parkinson's disease.
AB  - Parkinson's disease (PD) has been related to impaired processing of emotional
      speech intonation (emotional prosody). One distinctive feature of idiopathic PD
      is motor symptom asymmetry, with striatal dysfunction being strongest in the
      hemisphere contralateral to the most affected body side. It is still unclear
      whether this asymmetry may affect vocal emotion perception. Here, we tested 22 PD
      patients (10 with predominantly left-sided [LPD] and 12 with predominantly right
      sided motor symptoms) and 22 healthy controls in an event-related potential
      study. Sentences conveying different emotional intonations were presented in
      lexical and pseudo-speech versions. Task varied between an explicit and an
      implicit instruction. Of specific interest was emotional salience detection from
      prosody, reflected in the P200 component. We predicted that patients with
      predominantly right-striatal dysfunction (LPD) would exhibit P200 alterations.
      Our results support this assumption. LPD patients showed enhanced P200
      amplitudes, and specific deficits were observed for disgust prosody, explicit
      anger processing and implicit processing of happy prosody. Lexical speech was
      predominantly affected while the processing of pseudo-speech was largely intact.
      P200 amplitude in patients correlated significantly with left motor scores and
      asymmetry indices. The data suggest that emotional salience detection from
      prosody is affected by asymmetric neuronal degeneration in PD. 

PMID- 22956666
TI  - Structural face encoding: How task affects the N170's sensitivity to race.
AB  - The N170 event-related potential (ERP) component differentiates faces from non
      faces, but studies aimed at investigating whether the processing indexed by this
      component is also sensitive to racial differences among faces have garnered
      conflicting results. Here, we explore how task affects the influence of race on
      the N170 among White participants. N170s were larger to ingroup White faces than
      outgroup Black faces, but only for those required to attend to race, suggesting
      that attention to race can result in deeper levels of processing for ingroup
      members. Conversely, N170s were larger to Black faces than White faces for
      participants who attended to the unique identity of the faces, suggesting that
      attention to identity can result in preferential recruitment of cognitive
      resources for outgroup members. Taken together, these findings suggest that race
      can differentially impact face processing at early stages of encoding, but
      differences in processing are contingent upon one's goal state. 

PMID- 22956667
TI  - When psychopathy impairs moral judgments: neural responses during judgments about
      causing fear.
AB  - Psychopathy is a disorder characterized by reduced empathy, shallow affect and
      behaviors that cause victims distress, like threats, bullying and violence.
      Neuroimaging research in both institutionalized and community samples implicates
      amygdala dysfunction in the etiology of psychopathic traits. Reduced amygdala
      responsiveness may disrupt processing of fear-relevant stimuli like fearful
      facial expressions. The present study links amygdala dysfunction in response to
      fear-relevant stimuli to the willingness of individuals with psychopathic traits
      to cause fear in other people. Thirty-three healthy adult participants varying in
      psychopathic traits underwent whole-brain fMRI scanning while they viewed
      statements that selectively evoke anger, disgust, fear, happiness or sadness.
      During scanning, participants judged whether it is morally acceptable to make
      each statement to another person. Psychopathy was associated with reduced
      activity in right amygdala during judgments of fear-evoking statements and with
      more lenient moral judgments about causing fear. No group differences in amygdala
      function or moral judgments emerged for other emotion categories. Psychopathy was
      also associated with increased activity in middle frontal gyrus (BA 10) during
      the task. These results implicate amygdala dysfunction in impaired judgments
      about causing distress in psychopathy and suggest that atypical amygdala
      responses to fear in psychopathy extend across multiple classes of stimuli. 

PMID- 22956668
TI  - Who am I? How do I look? Neural differences in self-identity in anorexia nervosa.
AB  - Anorexia nervosa (AN) patients exhibit a disparity in their actual physical
      identity and their cognitive understanding of their physical identity. Functional
      magnetic resonance imaging (fMRI) tasks have contributed to understanding the
      neural circuitry involved in processing identity in healthy individuals. We
      hypothesized that women recovering from AN would show altered neural responses
      while thinking about their identity compared with healthy control women. We
      compared brain activation using fMRI in 18 women recovering from anorexia (RAN)
      and 18 healthy control women (CON) using two identity-appraisal tasks. These
      neuroimaging tasks were focused on separable components of identity: one
      consisted of adjectives related to social activities and the other consisted of
      physical descriptive phrases about one's appearance. Both tasks consisted of
      reading and responding to statements with three different perspectives: Self,
      Friend and Reflected. In the comparisons of the RAN and CON subjects, we observed
      differences in fMRI activation relating to self-knowledge ('I am', 'I look') and
      perspective-taking ('I believe', 'Friend believes') in the precuneus, two areas
      of the dorsal anterior cingulate, and the left middle frontal gyrus. These data
      suggest that further exploration of neural components related to identity may
      improve our understanding of the pathology of AN. 

PMID- 22956669
TI  - Specific neural correlates of successful learning and adaptation during social
      exchanges.
AB  - Cooperation and betrayal are universal features of social interactions, and
      knowing who to trust is vital in human society. Previous studies have identified
      brain regions engaged by decision making during social encounters, but the
      mechanisms supporting modification of future behaviour by utilizing social
      experience are not well characterized. Using functional magnetic resonance
      imaging (fMRI), we show that cooperation and betrayal during social exchanges
      elicit specific patterns of neural activity associated with future behaviour.
      Unanticipated cooperation leads to greater behavioural adaptation than unexpected
      betrayal, and is signalled by specific neural responses in the striatum and
      midbrain. Neural responses to betrayal and willingness to trust novel partners
      both decrease as the number of individuals encountered during repeated social
      encounters increases. We propose that, as social groups increase in size,
      uncooperative or untrustworthy behaviour becomes progressively less surprising,
      with cooperation becoming increasingly important as a stimulus for social
      learning. Effects on reputation of non-trusting decisions may also act to drive
      pro-social behaviour. Our findings characterize the dynamic neural processes
      underlying social adaptation, and suggest that the brain is optimized to
      cooperate with trustworthy partners, rather than avoiding those who might betray
      us. 

PMID- 22956670
TI  - Amygdala response to negative images in postpartum vs nulliparous women and
      intranasal oxytocin.
AB  - The neuroendocrine state of new mothers may alter their neural processing of
      stressors in the environment through modulatory actions of oxytocin on the limbic
      system. We predicted that amygdala sensitivity to negatively arousing stimuli
      would be suppressed in postpartum compared to nulliparous women and that this
      suppression would be modulated by administration of oxytocin nasal spray. We
      measured brain activation (fMRI) and subjective arousal in response to negatively
      arousing pictures in 29 postpartum and 30 nulliparous women who received either
      oxytocin nasal spray or placebo before scanning. Pre- and post-exposure urinary
      cortisol levels were also measured. Postpartum women (placebo) demonstrated lower
      right amygdala activation in response to negative images, lower cortisol and
      lower negative photo arousal ratings to nulliparous women. Nulliparous women
      receiving oxytocin had lower right amygdala activation compared to placebo.
      Cortisol levels in the placebo group, and ratings of arousal across all women,
      were positively associated with right amygdala activation. Together, these
      findings demonstrate reductions in both amygdala activation and subjective
      negative arousal in untreated postpartum vs nulliparous women, supporting the
      hypothesis of an attenuated neural response to arousing stimuli in postpartum
      women. A causal role of oxytocin and the timing of potential effects require
      future investigation. 

PMID- 22956671
TI  - Fact vs fiction--how paratextual information shapes our reading processes.
AB  - Our life is full of stories: some of them depict real-life events and were
      reported, e.g. in the daily news or in autobiographies, whereas other stories, as
      often presented to us in movies and novels, are fictional. However, we have only
      little insights in the neurocognitive processes underlying the reading of factual
      as compared to fictional contents. We investigated the neurocognitive effects of
      reading short narratives, labeled to be either factual or fictional. Reading in a
      factual mode engaged an activation pattern suggesting an action-based
      reconstruction of the events depicted in a story. This process seems to be past
      oriented and leads to shorter reaction times at the behavioral level. In
      contrast, the brain activation patterns corresponding to reading fiction seem to
      reflect a constructive simulation of what might have happened. This is in line
      with studies on imagination of possible past or future events. 

PMID- 22956672
TI  - Linkage of functional and structural anomalies in the left amygdala of reactive
      aggressive men.
AB  - Amygdala structural and functional abnormalities have been associated to reactive
      aggression in previous studies. However, the possible linkage of these two types
      of anomalies has not been examined. We hypothesized that they would coincide in
      the same localizations, would be correlated in intensity and would be mediated by
      reactive aggression personality traits. Here violent (n = 25) and non-violent (n
      = 29) men were recruited on the basis of their reactive aggression. Callous
      unemotional (CU) traits were also assessed. Gray matter concentration (gmC) and
      reactivity to fearful and neutral facial expressions were measured in dorsal and
      ventral amygdala partitions. The difference between responses to fearful and
      neutral facial expressions was calculated (F/N-difference). Violent individuals
      exhibited a smaller F/N-difference and gmC in the left dorsal amygdala, where a
      significant coincidence was found in a conjunction analysis. Moreover, the left
      amygdala F/N-difference and gmC were correlated to each other, an effect mediated
      by reactive aggression but not by CU. The F/N-difference was caused by increased
      reactivity to neutral faces. This suggests that anatomical anomalies within local
      circuitry (and not only altered input) may underlie the amygdala hyper-reactivity
      to social signals which is characteristic of reactive aggression. 

PMID- 22956673
TI  - The neural basis of belief updating and rational decision making.
AB  - Rational decision making under uncertainty requires forming beliefs that
      integrate prior and new information through Bayes' rule. Human decision makers
      typically deviate from Bayesian updating by either overweighting the prior
      (conservatism) or overweighting new information (e.g. the representativeness
      heuristic). We investigated these deviations through measurements of
      electrocortical activity in the human brain during incentivized probability
      updating tasks and found evidence of extremely early commitment to boundedly
      rational heuristics. Participants who overweight new information display a lower
      sensibility to conflict detection, captured by an event-related potential (the
      N2) observed around 260 ms after the presentation of new information.
      Conservative decision makers (who overweight prior probabilities) make up their
      mind before new information is presented, as indicated by the lateralized
      readiness potential in the brain. That is, they do not inhibit the processing of
      new information but rather immediately rely on the prior for making a decision. 

PMID- 22956674
TI  - Trust at first sight: evidence from ERPs.
AB  - We used event-related potentials (ERPs) to tap the temporal dynamics of first
      impressions based on face appearance. Participants were asked to evaluate briefly
      presented faces for trustworthiness and political choice. Behaviorally,
      participants were better at discriminating faces that were pre-rated as
      untrustworthy. The ERP results showed that the P100 component was enhanced for
      untrustworthy faces, consistently with the view that signals of potential threat
      are given precedence in neural processing. The enhanced ERP responses to
      untrustworthy faces persisted throughout the processing sequence and the
      amplitude of early posterior negativity (EPN), and subsequent late positive
      potential (LPP) was increased with respect to trustworthy faces which, in
      contrast, elicited an enhanced positivity around 150 ms on frontal sites. These
      ERP patterns were found specifically for the trustworthiness evaluation and not
      for the political decision task. Political decision yielded an increase in the
      N170 amplitude, reflecting a more demanding and taxing structural encoding.
      Similar ERP responses, as previously reported in the literature for facial
      expressions processing, were found throughout the entire time course specifically
      elicited by faces explicitly judged as untrustworthy. One possibility might be
      that evolution has provided the brain with a 'special toolkit' for trust
      evaluation that is fast and triggers ERPs related to emotional processing. 

PMID- 22956675
TI  - 'Put on your poker face': neural systems supporting the anticipation for
      expressive suppression and cognitive reappraisal.
AB  - It is a unique human ability to regulate negative thoughts and feelings. Two well
      investigated emotion-regulation strategies (ERSs), cognitive reappraisal and
      expressive suppression, are associated with overlapping prefrontal neural
      correlates, but differ temporally during the emotion-generation process. Although
      functional imaging studies have mainly investigated these ERS as a reaction to an
      emotion-inducing event, the intention to regulate upcoming negative emotions
      might already be associated with differences in neural activity. Hence, event
      related functional magnetic resonance imaging was recorded in 42 participants
      while they completed an emotion-regulation paradigm. During this task,
      participants were instructed to proactively prepare to use a specific ERS knowing
      that a negative, high-arousing image would appear after the preparation period.
      As expected, the results demonstrated prefrontal and parietal activation while
      participants were suppressing or reappraising their emotions (family-wise error
      (FWE)-corrected). The intention to suppress emotions was associated with
      increased activation in the right inferior frontal gyrus, bilateral putamen, pre
      supplementary motor area and right supramarginal gyrus (FWE-corrected). This
      enhanced proactive inhibitory control: (i) predicted decreased motoric activity
      during the actual suppression of emotional expressions and (2) trended toward a
      significant association with how successfully participants suppressed their
      emotions. However, neural correlates of preparatory control for cognitive
      reappraisal were not observed, possibly because contextual cues about the
      upcoming emotional stimulus are necessary to proactively start to cognitively
      reinterpret the situation. 

PMID- 22956676
TI  - Compassion meditation enhances empathic accuracy and related neural activity.
AB  - The ability to accurately infer others' mental states from facial expressions is
      important for optimal social functioning and is fundamentally impaired in social
      cognitive disorders such as autism. While pharmacologic interventions have shown
      promise for enhancing empathic accuracy, little is known about the effects of
      behavioral interventions on empathic accuracy and related brain activity. This
      study employed a randomized, controlled and longitudinal design to investigate
      the effect of a secularized analytical compassion meditation program, cognitive
      based compassion training (CBCT), on empathic accuracy. Twenty-one healthy
      participants received functional MRI scans while completing an empathic accuracy
      task, the Reading the Mind in the Eyes Test (RMET), both prior to and after
      completion of either CBCT or a health discussion control group. Upon completion
      of the study interventions, participants randomized to CBCT and were
      significantly more likely than control subjects to have increased scores on the
      RMET and increased neural activity in the inferior frontal gyrus (IFG) and
      dorsomedial prefrontal cortex (dmPFC). Moreover, changes in dmPFC and IFG
      activity from baseline to the post-intervention assessment were associated with
      changes in empathic accuracy. These findings suggest that CBCT may hold promise
      as a behavioral intervention for enhancing empathic accuracy and the neurobiology
      supporting it.

PMID- 22956677
TI  - Special issue on mindfulness neuroscience.

PMID- 22956679
TI  - 'I do not need a flu shot because I lead a healthy lifestyle': compensatory
      health beliefs make vaccination less likely.
AB  - Compensatory health beliefs, a self-defence strategy, were examined in a theory
      guided intervention promoting influenza vaccination at the workplace. In total,
      851 employees were randomised to one group aimed at enhancing intention formation
      (standard group) or to another one assisting self-regulation (intervention
      group). Assessments took place after the intervention and 5 months later,
      investigating whether the intervention would interfere with compensatory health
      beliefs. The intervention generated an indirect effect via planning on
      vaccination. Compensatory health beliefs mediated between intention and
      behaviour. An interaction between intervention group and compensatory health
      beliefs on behaviour transpired. At low compensatory health belief levels, the
      intervention group resulted in more vaccinations than the standard group.

PMID- 22956678
TI  - Sociocultural patterning of neural activity during self-reflection.
AB  - Western cultures encourage self-construals independent of social contexts,
      whereas East Asian cultures foster interdependent self-construals that rely on
      how others perceive the self. How are culturally specific self-construals
      mediated by the human brain? Using functional magnetic resonance imaging, we
      monitored neural responses from adults in East Asian (Chinese) and Western
      (Danish) cultural contexts during judgments of social, mental and physical
      attributes of themselves and public figures to assess cultural influences on self
      referential processing of personal attributes in different dimensions. We found
      that judgments of self vs a public figure elicited greater activation in the
      medial prefrontal cortex (mPFC) in Danish than in Chinese participants regardless
      of attribute dimensions for judgments. However, self-judgments of social
      attributes induced greater activity in the temporoparietal junction (TPJ) in
      Chinese than in Danish participants. Moreover, the group difference in TPJ
      activity was mediated by a measure of a cultural value (i.e. interdependence of
      self-construal). Our findings suggest that individuals in different sociocultural
      contexts may learn and/or adopt distinct strategies for self-reflection by
      changing the weight of the mPFC and TPJ in the social brain network. 

PMID- 22956680
TI  - Chinese parental perceptions of weight and associated health risks of young
      children.
AB  - A mixed method was employed to determine how caregivers view preschool children's
      body size and associated health risks. A survey of 505 caregivers was nested in
      10 in-depth case studies of mothers. Based on the International Obesity Task
      Force calculation of children's weight status, the caregivers who had underweight
      children overestimated their children's weight status but the caregivers who had
      overweight/obese children underestimated their children's weight status. Their
      estimates were substantially different from those of the caregivers of normal
      weight children. The mothers' thoughts revealed the complexity of beliefs and
      sociocultural experiences about weight preferences and affirmed the quantitative
      findings.

PMID- 22956681
TI  - Relation between comparative risk, absolute risk, and worry: the role of
      handedness strength.
AB  - Research is mixed regarding whether comparative or absolute risk perceptions are
      most associated with important outcomes (e.g. worry). The current research
      examined the role of individual differences in organizational brain structure and
      connectivity-assessed via handedness strength-in moderating these effects. Strong
      handers and mixed handers made comparative and absolute risk estimates for
      contracting a sexually transmitted disease or sexually transmitted infection and
      also indicated their worry. Additionally, participants indicated whether they
      received testing for sexually transmitted diseases or sexually transmitted
      infections. For strong handers, absolute risk perceptions were generally more
      associated with worry and testing behaviors, whereas for mixed handers,
      comparative risk perceptions were more associated.

PMID- 22956682
TI  - A cognitive-perceptual model of symptom perception in males and females: the
      roles of negative affect, selective attention, health anxiety and psychological
      job demands.
AB  - Kolk et al.'s model of symptom perception underlines the effects of trait
      negative affect, selective attention and external stressors. The current study
      tested this model in 263 males and 498 females from an occupational sample. Trait
      negative affect was associated with symptom reporting in females only, and
      selective attention and psychological job demands were associated with symptom
      reporting in both genders. Health anxiety was associated with symptom reporting
      in males only. Future studies might consider the inclusion of selective
      attention, which was more strongly associated with symptom reporting than
      negative affect. Psychological job demands appear to influence symptom reporting
      in both males and females.

PMID- 22956683
TI  - Brief report: effect of dietary restraint on fruit and vegetable intake following
      implementation intentions.
AB  - This study explored whether the effects of implementation intentions on
      increasing fruit and vegetable intake were moderated by dietary restraint. In
      total, 208 participants were randomly allocated to control or implementation
      intention conditions where they were asked to write down when, where and how they
      would increase their fruit and vegetable intake. Implementation intentions
      increased fruit and vegetable intake but only in participants scoring low (not
      high) on rigid dietary restraint. Motives underlying fruit and vegetable
      consumption may be different for restrained and unrestrained eaters. Efforts to
      increase their intake may need to be tailored, for example, through motivational
      rather than situational cues.

PMID- 22956685
TI  - Relaxation and prethermalization in an isolated quantum system.
AB  - Understanding relaxation processes is an important unsolved problem in many areas
      of physics. A key challenge is the scarcity of experimental tools for the
      characterization of complex transient states. We used measurements of full
      quantum mechanical probability distributions of matter-wave interference to study
      the relaxation dynamics of a coherently split one-dimensional Bose gas and
      obtained comprehensive information about the dynamical states of the system.
      After an initial rapid evolution, the full distributions reveal the approach
      toward a thermal-like steady state characterized by an effective temperature that
      is independent from the initial equilibrium temperature of the system before the
      splitting process. We conjecture that this state can be described through a
      generalized Gibbs ensemble and associate it with prethermalization.

PMID- 22956684
TI  - Wnt5a potentiates TGF-beta signaling to promote colonic crypt regeneration after
      tissue injury.
AB  - Reestablishing homeostasis after tissue damage depends on the proper organization
      of stem cells and their progeny, though the repair mechanisms are unclear. The
      mammalian intestinal epithelium is well suited to approach this problem, as it is
      composed of well-delineated units called crypts of Lieberkuhn. We found that
      Wnt5a, a noncanonical Wnt ligand, was required for crypt regeneration after
      injury in mice. Unlike controls, Wnt5a-deficient mice maintained an expanded
      population of proliferative epithelial cells in the wound. We used an in vitro
      system to enrich for intestinal epithelial stem cells to discover that Wnt5a
      inhibited proliferation of these cells. Surprisingly, the effects of Wnt5a were
      mediated by activation of transforming growth factor-beta (TGF-beta) signaling.
      These findings suggest a Wnt5a-dependent mechanism for forming new crypt units to
      reestablish homeostasis.

PMID- 22956686
TI  - Mutations in BCKD-kinase lead to a potentially treatable form of autism with
      epilepsy.
AB  - Autism spectrum disorders are a genetically heterogeneous constellation of
      syndromes characterized by impairments in reciprocal social interaction.
      Available somatic treatments have limited efficacy. We have identified
      inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase
      Kinase) in consanguineous families with autism, epilepsy, and intellectual
      disability. The encoded protein is responsible for phosphorylation-mediated
      inactivation of the E1alpha subunit of branched-chain ketoacid dehydrogenase
      (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK
      messenger RNA and protein, E1alpha phosphorylation, and plasma branched-chain
      amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and
      neurobehavioral deficits that respond to dietary supplementation. Thus, autism
      presenting with intellectual disability and epilepsy caused by BCKDK mutations
      represents a potentially treatable syndrome.

PMID- 22956688
TI  - Primary care research conducted in networks: getting down to business.
AB  - This seventh annual practice-based research theme issue of the Journal of the
      American Board of Family Medicine highlights primary care research conducted in
      practice-based research networks (PBRNs). The issue includes discussion of (1)
      theoretical and methodological research, (2) health care research (studies
      addressing primary care processes), (3) clinical research (studies addressing the
      impact of primary care on patients), and (4) health systems research (studies of
      health system issues impacting primary care including the quality improvement
      process). We had a noticeable increase in submissions from PBRN collaborations,
      that is, studies that involved multiple networks. As PBRNs cooperate to recruit
      larger and more diverse patient samples, greater generalizability and
      applicability of findings lead to improved primary care processes.

PMID- 22956687
TI  - Evidence of abundant purifying selection in humans for recently acquired
      regulatory functions.
AB  - Although only 5% of the human genome is conserved across mammals, a substantially
      larger portion is biochemically active, raising the question of whether the
      additional elements evolve neutrally or confer a lineage-specific fitness
      advantage. To address this question, we integrate human variation information
      from the 1000 Genomes Project and activity data from the ENCODE Project. A broad
      range of transcribed and regulatory nonconserved elements show decreased human
      diversity, suggesting lineage-specific purifying selection. Conversely, conserved
      elements lacking activity show increased human diversity, suggesting that some
      recently became nonfunctional. Regulatory elements under human constraint in
      nonconserved regions were found near color vision and nerve-growth genes,
      consistent with purifying selection for recently evolved functions. Our results
      suggest continued turnover in regulatory regions, with at least an additional 4%
      of the human genome subject to lineage-specific constraint.

PMID- 22956689
TI  - Measuring the impact of practice-based research networks (PBRNs).

PMID- 22956690
TI  - Lessons learned and challenges ahead: report from the OCHIN Safety Net West
      practice-based research network (PBRN).
AB  - INTRODUCTION: We recently completed a strategic planning process to better
      understand the development of our 5-year-old practice-based research network
      (PBRN) and to identify gaps between our original vision and current progress.
      Although many of our experiences are not new to the PBRN community, our
      reflections may be valuable for those developing or reshaping PBRNs in a changing
      health care environment. LESSONS LEARNED: We learned about the importance of (1)
      shared vision and commitment to a unique patient population; (2) strong
      leadership, mentorship, and collaboration; (3) creative approaches to engaging
      busy clinicians and bridging the worlds of academia and community practice; and
      (4) harnessing data from electronic health records and navigating processes
      related to data protection, sharing, and ownership. CHALLENGES AHEAD: We must
      emphasize research that is timely, relevant, and integrated into practice. One
      model supporting this goal involves a broader partnership than was initially
      envisioned for our PBRN--one that includes clinicians, researchers, information
      architects, and quality improvement experts partnering to develop an innovation
      center. This center could facilitate development of relevant research questions
      while also addressing "quick-turnaround" needs. CONCLUSIONS: Gaps remain between
      our PBRN's initial vision and current reality. Closing these gaps may require
      future creativity in building partnerships and finding nontraditional funding
      sources.

PMID- 22956691
TI  - Supporting better science in primary care: a description of practice-based
      research networks (PBRNs) in 2011.
AB  - BACKGROUND: Bound by a shared commitment to improving medical care through
      systematic inquiry, practice-based research networks (PBRNs) provide a basic
      laboratory for primary care research and dissemination. METHODS: Data from US
      primary care PBRNs were collected as part of the 2011 Agency for Healthcare
      Research and Quality PBRN registration process. Data addressed PBRN
      characteristics, research activities, and perceived strengths and weaknesses.
      RESULTS: One hundred forty-three primary care PBRNs were registered with the
      resource center in 2011, including 131 that were identified as either eligible
      for Agency for Healthcare Research and Quality recognition (n = 121) or as
      developing (n = 10). These PBRNs included 12,981 practices with more than 63,000
      individual members providing care to approximately 47.5 million people. PBRNs had
      an average of 482 individual members (median, 170) from 101 practices (median,
      32). CONCLUSIONS: PBRNs are growing in experience and research capacity. With
      member practices serving approximately 15% of the US population, PBRNs are
      adopting more advanced study designs, disseminating and implementing practice
      change, and participating in clinical trials. PBRNs provide valuable capacity for
      investigating questions of importance to clinical practice, disseminating
      results, and implementing evidence-based strategies. PBRNs are well positioned to
      support the emerging public health role of primary care providers and provide an
      essential component of a learning health care system.

PMID- 22956692
TI  - Practice-based research networks (PBRNs): meeting the challenges of the future.
AB  - Practice-based research networks (PBRNs) are useful tools for conducting studies
      in the busy primary care setting, but their continued existence is threatened by
      a range of challenges. PBRNs must position themselves now to be prepared to face
      the challenges ahead. For example, experience with the Clinical Translational
      Science Awards has placed PBRNs at the center of university efforts toward
      greater community engagement. Networks must use this opportunity to solicit
      infrastructure support and partner with experienced principal investigators from
      other disciplines. Successful networks must make greater use of health
      information technology to solicit clinician involvement, identify and recruit
      potential subjects, and disseminate key findings. To maintain the active
      participation of busy clinicians in the clinical research enterprise, networks
      must find new ways to engage their members and simplify study participation.
      Networks should pursue clinically relevant projects that create meaning and
      connect busy practitioners to the larger agenda of primary care research.
      Finally, collaborating with other networks in a structured and ongoing manner is
      one way for PBRNs to extend their reach while making maximal use of their unique
      resources and local expertise.

PMID- 22956693
TI  - Coordinating centers and multi-practice-based research network (PBRN) research.
AB  - Practice-based research networks (PBRNs) have emerged as laboratories in which to
      address important primary care challenges. In 2011, the Agency for Healthcare
      Research and Quality's PBRN database included more than 130 networks, most
      regional and some national, with member practices in every state. Regional
      networks may have certain advantages over national networks with respect to
      practice recruitment and project quality control because of closer relationships
      and shorter distances. However, national networks often can achieve larger
      numbers of practices with greater diversity, resulting in broader
      generalizability of results. Increasingly, regional networks are collaborating on
      multinetwork projects, but this creates significant study coordination
      challenges. A potential solution is to incorporate PBRN coordinating centers
      similar to those used in many National Institutes of Health and industry
      sponsored multi-center clinical trials. In this article, we discuss the potential
      functions of a coordinating center in multi-region PBRN studies based on our
      experience with 2 recent studies.

PMID- 22956694
TI  - Enhancing electronic health record measurement of depression severity and suicide
      ideation: a Distributed Ambulatory Research in Therapeutics Network (DARTNet)
      study.
AB  - BACKGROUND: Depression is a leading cause of morbidity worldwide. The majority of
      treatment for depression occurs in primary care, but effective care remains
      elusive. Clinical decision making and comparative studies of real-world
      antidepressant effectiveness are limited by the absence of clinical measures of
      severity of illness and suicidality. METHODS: The Distributed Ambulatory Research
      in Therapeutics Network (DARTNet) was engaged to systematically collect data
      using the 9-item Patient Health Questionnaire (PHQ-9) at the point of care. We
      used electronic health records (EHRs) and the PHQ-9 to capture, describe, and
      compare data on both baseline severity of illness and suicidality and response
      and suicidality after diagnosis for depressed patients in participating DARTNet
      practices. RESULTS: EHR data were obtained for 81,028 episodes of depression
      (61,464 patients) from 14 clinical organizations. Over 9 months, data for 4900
      PHQ-9s were collected from 2969 patients in DARTNet practices (this included 1892
      PHQ-9s for 1019 adults and adolescents who had at least one depression
      diagnosis). Only 8.3% of episodes identified in our depression cohort had
      severity of illness information available in the EHR. For these episodes,
      considerable variation existed in both severity of illness (32.05% with no
      depression, 26.89% with minimal, 19.54% with mild, 12.04% with moderate, and
      9.47% with severe depression) and suicidality (69.43% with a score of 0, 22.58%
      with a score of 1, 4.97% with a score of 2, and 3.02% with a score of 3 on item 9
      of the PHQ-9). Patients with an EHR diagnosis of depression and a PHQ-9 (n =
      1019) had similar severity but slightly higher suicidality levels compared with
      all patients for which PHQ-9 data were available. The PHQ-9 showed higher
      sensitivity for identifying depression response and emergent (after diagnosis)
      severity and suicidality; 25% to 30% of subjects had some degree of suicidal
      thought at some point in time according to the PHQ-9. CONCLUSIONS: This study
      demonstrated the value of adding PHQ-9 data and prescription fulfillment data to
      EHRs to improve diagnosis and management of depression in primary care and to
      enable more robust comparative effectiveness research on antidepressants.

PMID- 22956695
TI  - Implementing and evaluating electronic standing orders in primary care practice:
      a PPRNet study.
AB  - BACKGROUND: A standing order (SO) authorizes nurses and other staff to carry out
      medical orders per practice-approved protocol without a clinician's examination.
      This study implemented electronic SOs into the daily workflow of primary care
      practices; identified methods and strategies; determined barriers and
      facilitators; and measured changes in quality indicators resulting from
      electronic SOs. METHODS: Within 8 practices using the Practice Partner(r)
      electronic health record (EHR), a customized health maintenance template provided
      SOs for screening, immunization, and diabetes measures. EHR data extracts were
      used to calculate the presence and use of these measures on health maintenance
      templates and performance over 21 months. Qualitative observation/interviews at
      practice site visits, network meetings, and correspondence enabled synthesis of
      implementation issues. RESULTS: Improvements in template presence, use, and
      performance were found for 14 measures across all practices. Median improvements
      in screening ranged 6% to 10%; immunizations, 8% to 17%, and diabetes, 0% to 18%.
      Two practices achieved significant improvement on 14 of the 15 measures. All
      practices significantly improved on at least 3 of the measures. CONCLUSIONS: A
      small sample of primary care practices implemented SOs for screening,
      immunizations and diabetes measures supported by PPRNet researchers. Technical
      competence and leadership to adapt EHR reminder tools helped staff adopt new
      roles and overcome barriers.

PMID- 22956697
TI  - The relationship of self-report of quality to practice size and health
      information technology.
AB  - BACKGROUND: Assessment of patient safety culture has recently expanded in
      inpatient settings, but the majority of medical encounters occurs in office
      settings, and less is known about the determinants of perceived quality and
      safety in ambulatory care. The Medical Office Survey of Patient Safety was
      developed to assess perceived quality of care and patient safety culture in
      medical offices, including a domain to assess the quality criteria as defined by
      the Institute of Medicine: patient-centered, effective, timely, efficient, and
      equitable. METHODS: We surveyed 6534 clinicians and staff in 306 medical
      practices from 11 practice based research networks (PBRNs) in 16 states. We
      collected data on office size, ownership, and use of health information
      technologies (HIT) and assessed perceived patient safety and quality of care with
      the Medical Office Survey of Patient Safety's overall quality domain. Using a
      mixed model that adjusted for the role of respondents, we examined the
      relationship between perceived safety and quality of care and office size,
      ownership, and the degree of implementation of HIT. RESULTS: Small practices (3
      15 personnel) reported the highest proportion of positive perceptions of quality
      and safety. The lowest proportion of positive perceptions of quality and safety
      occurred in large (41-70 personnel) and very large practices (>70 personnel).
      After controlling for office size, we found no relationship between perceived
      quality and safety and practice ownership. The relationship of HIT implementation
      to perceived quality and safety was not clear. We found the highest proportion of
      positive perceptions in practices with the least HIT and those with the most HIT
      and the lowest proportion in practices with intermediate levels of HIT.
      CONCLUSIONS: Personnel in small practices reported the highest overall quality
      and safety of care, and perceived quality and safety declined with increasing
      office size. No clear relationship was found between perceived quality and safety
      and implementation of HIT.

PMID- 22956696
TI  - Evaluation of a screening and counseling tool for alcohol misuse: a Virginia
      Practice Support and Research Network (VaPSRN) trial.
AB  - BACKGROUND: Surveys reveal limited screening and counseling for alcohol misuse by
      primary care physicians despite evidence-based recommendations. We developed and
      evaluated an alcohol screening and misuse counseling tool designed to assist
      clinicians at the point of care (POC). METHODS: This was a mixed methods,
      prospective cohort study conducted with licensed clinicians in a practice-based
      research network. A software tool was designed to guide clinicians through
      evidence-based alcohol misuse assessment and interventions. RESULTS: Participants
      (N = 12) used the tool an average of 3 sessions and 71% were satisfied with the
      tool. Participants increased their ability to differentiate between patients who
      are "at risk" drinkers versus those with alcohol use disorders including
      dependence/abuse (21%; t = 2.4; P = .04). Thematic analysis of interviews
      suggests that barriers to overall use included perceptions of alcohol use;
      clinical need to intervene; time; and issues with use of technology, most often
      at the POC. However, the tool added confidence and a valuable framework for
      interventions and was valued as an educational tool. Users felt that increased
      training and practice could increase comfort and impact future POC use. Increased
      POC usability also may be achieved through simplification of the tool and
      additional flexibility in options for POC use. CONCLUSIONS: A computer-assisted
      counseling tool for alcohol misuse and abuse can be implemented in primary care
      settings and shows promise for improving physician screening and interventions
      for alcohol misuse. To enhance utility in daily clinical practice we recommend
      design enhancements and strategies to enhance usage as described in this
      research.

PMID- 22956698
TI  - Communication technology access, use, and preferences among primary care
      patients: from the Residency Research Network of Texas (RRNeT).
AB  - OBJECTIVE: The digital revolution is changing the manner in which patients
      communicate with their health care providers, yet many patients still lack access
      to communication technology. We conducted this study to evaluate access to, use
      of, and preferences for using communication technology among a predominantly low
      income patient population. We determined whether access, use, and preferences
      were associated with type of health insurance, sex, age, and ethnicity. METHODS:
      In 2011, medical student researchers administered questionnaires to patients of
      randomly selected physicians within 9 primary care clinics in the Residency
      Research Network of Texas. Surveys addressed access to and use of cell phones and
      home computers and preferences for communicating with health care providers.
      RESULTS: In this sample of 533 patients (77% response rate), 448 (84%) owned a
      cell phone and 325 (62%) owned computers. Only 48% reported conducting Internet
      searches, sending and receiving E-mails, and looking up health information on the
      Internet. Older individuals, those in government sponsored insurance programs,
      and individuals from racial/ethnic minority groups had the lowest levels of
      technology adoption. In addition, more than 60% of patients preferred not to send
      and receive health information over the Internet, by instant messaging, or by
      text messaging. CONCLUSIONS: Many patients in this sample did not seek health
      information electronically nor did they want to communicate electronically with
      their physicians. This finding raises concerns about the vision of the patient
      centered medical home to enhance the doctor-patient relationship through
      communication technology. Our patients represent some of the more vulnerable
      populations in the United States and, as such, deserve attention from health care
      policymakers who are promoting widespread use of communication technology.

PMID- 22956699
TI  - Primary care providers' needs and preferences for information about colorectal
      cancer survivorship care.
AB  - BACKGROUND: The Institute of Medicine (IOM) proposed that cancer survivors and
      their primary care providers (PCPs) should receive survivorship care plans to
      inform ongoing care. We aimed to determine PCPs' preferences for the content of
      survivorship care plans for colorectal cancer (CRC) survivors. METHODS: PCPs in 3
      practice-based research networks completed a survey regarding 45 topics of CRC
      information based on the IOM's survivorship care plan framework. RESULTS: One
      hundred fifty-six PCPs completed the survey. For 35 topics (78%), at least half
      of respondents felt the topic was very important. Most PCPs reported receiving
      too little information about problems with chemotherapy (68%) or radiation (60%)
      and whether the oncologist intended to monitor for other cancers (71%). PCPs
      widely agreed that they do not have enough information about increased risk of
      second CRCs, other cancers, and other diseases (78%); long-term effects of
      chemotherapy (73%) and radiation (67%); and genetic counseling (83%).
      CONCLUSIONS: PCPs endorse the IOM's survivorship care plan framework as relevant
      and often report needing more information. Survivorship care plans may provide
      important information to PCPs by communicating patients' cancer histories and
      making recommendations regarding which aspects of care should be provided by the
      oncologist or the PCP.

PMID- 22956700
TI  - Care for patients with chronic nonmalignant pain with and without chronic opioid
      prescriptions: a report from the Cincinnati Area Research Group (CARinG) network.
AB  - BACKGROUND: The use of chronic opioids for patients with chronic nonmalignant
      pain (CNMP) is a common problem for family physicians, yet little is known about
      the management of CNMP in family medicine offices. METHODS: Twenty one physicians
      at 8 practices of the Cincinnati Area Research Group (CARinG) network completed
      25 to 30 modified Primary Care Network Survey 2 surveys. Each survey contained
      the question, "To your knowledge, does this patient have chronic (>3 months)
      pain, even if they are not being seen for pain today?" Chart reviews of all
      patients identified as having chronic pain were performed to examine assessment,
      management, and monitoring of chronic opioids. Ten of these physicians and 10
      office nurses or medical assistants were interviewed about caring for patients
      with chronic pain. RESULTS: Primary Care Network Survey 2 questionnaires were
      completed for 533 patients, 138 (26%) of which had CNMP, and 65 (47%) of those
      were taking chronic opioids; 25% of patients taking chronic opioids had a urine
      drug screen and 22% had an opioid contract in the chart. Patients with CNMP who
      were taking chronic opioids were more likely to be younger (54 vs 59 years; P =
      .003), have a coexisting mental health diagnosis (69% vs 44%; P = .005), and have
      assessments for pain (P = .031), function (P = .003), and psychological distress
      (P < .001) and a second opinion (P = .001) in the chart than did patients with
      CNMP who were not taking opioids. Physicians described suspicion of patients as a
      primary difficulty in prescribing or considering chronic opioids; they also
      expressed interest in practicing evidence-based CNMP care, but there was little
      teamwork between physicians and medical assistants caring for patients with CNMP
      who were taking chronic opioids. CONCLUSIONS: Chronic opioids are frequently
      prescribed to patients with CNMP. Although patients taking opioids have better
      documentation of pain assessments and management, care for all patients with CNMP
      fell short of evidence-based guidelines and was primarily performed by the
      physician alone.

PMID- 22956701
TI  - Contraceptive methods and informed consent among women receiving medications with
      potential for adverse fetal effects: a Washington, Wyoming, Alaska, Montana,
      Idaho (WWAMI) region study.
AB  - BACKGROUND: Increasing diabetes, hypertension, and hypercholesterolemia rates
      expose some young women to medications with potential adverse fetal effects, such
      as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor
      blockers (ARBs), and statins. This study examined whether quality improvement
      (QI) interventions promote informed consent and contraception to minimize risks
      with use of ACE-I/ARB/statins. METHODS: This longitudinal cohort study at 7
      clinics abstracted medical records of 328 women aged 18 to 44 with >=1
      prescription for ACE-I/ARB/statins and >=1 visit for hypertension, diabetes, or
      hypercholesterolemia during the previous year. We measured informed consent
      documentation and contraceptive methods before and after QI interventions in
      which providers contacted their patients to discuss medication risks and
      benefits. RESULTS: Of 179 women who were not surgically sterilized, only 11.7%
      had documented informed consent related to the risks of ACE-I/ARB/statin use. One
      hundred fifty-eight women were eligible for the QI intervention (not surgically
      sterilized, no documented informed consent); only 76 (48.1%) received the
      intervention. Before the intervention, 23.7% of these 76 were "at risk" of an
      adverse fetal effect. After the intervention, only 7.9% (P <= .001) were "at
      risk" because some women started contraception, discontinued ACE-I/ARB/statins,
      or changed drug class. CONCLUSIONS: Women prescribed ACE-I/ARB/statins were not
      consistently using contraception or were not consistently informed of the risks.
      Provider-implemented QI interventions improved care but were difficult to
      accomplish, suggesting that new interventions are needed.

PMID- 22956702
TI  - Difficult encounters with psychiatric patients: a South Texas Psychiatry practice
      based research network (PBRN) study.
AB  - PURPOSE: To examine the prevalence of difficult psychiatrist-patient interactions
      of 20 psychiatrists in the South Texas Psychiatric practice-based research
      network, determine what characteristics were associated with "difficult"
      patients, and compare findings with previous studies in primary care. METHODS:
      During a 2-month observational study, psychiatrists collected patient information
      on setting, demographics, diagnoses, and medications and rated the patients using
      the Difficult Doctor-Patient Relationship Questionnaire, which had previously
      been used and validated in the primary care setting. RESULTS: A total of 905
      valid data cards were collected. Difficult patients were identified in 15% of the
      sample. Diagnoses of schizophrenia, alcohol/substance abuse, and personality
      disorder were associated with difficulty. Psychiatrists least burdened by
      difficult patients were older and in a solo practice and worked 51 to 55 hours
      per week. CONCLUSIONS: This cross-sectional study demonstrates that psychiatrists
      encounter difficult patients at a rate (15%) similar to that of primary care
      physicians. Mentoring programs and structured treatment interventions for the
      most difficult patient groups may assist all physicians who treat psychiatric
      patients, whether in specialty, family medicine, or other primary care settings.

PMID- 22956703
TI  - The role of the champion in primary care change efforts: from the State Networks
      of Colorado Ambulatory Practices and Partners (SNOCAP).
AB  - BACKGROUND: Change champions are important for moving new innovations through the
      phases of initiation, development, and implementation. Although research
      attributes positive health care changes to the help of champions, little work
      provides details about the champion role. METHODS: Using a combination of
      immersion/crystallization and matrix techniques, we analyzed qualitative data,
      which included field notes of team meetings, interviews, and transcripts of
      facilitator meetings, from a sample of 8 practices. RESULTS: Our analysis yielded
      insights into the value of having 2 discrete types of change champions: (1) those
      associated with a specific project (project champions) and (2) those leading
      change for entire organizations (organizational change champions). Relative to
      other practices under study, those that had both types of champions who
      complemented each other were best able to implement and sustain diabetes care
      processes. We provide insights into the emergence and development of these
      champion types, as well as key qualities necessary for effective championing.
      CONCLUSIONS: Practice transformation requires a sustained improvement effort that
      is guided by a larger vision and commitment and assures that individual changes
      fit together into a meaningful whole. Change champions--both project and
      organizational change champions--are critical players in supporting both
      innovation-specific and transformative change efforts.

PMID- 22956705
TI  - Use of the Americans in Motion-Healthy Intervention (AIM-HI) to create a culture
      of fitness in family practice.
AB  - BACKGROUND: Americans in Motion-Healthy Interventions (AIM-HI) is an initiative
      designed to assist family physicians with positioning fitness (physical activity,
      nutrition, and emotional well-being) as the treatment of choice for prevention
      and management of chronic disease. We investigated whether the concept of a
      culture of fitness would benefit office personnel and carry over to patient care.
      METHODS: This randomized, controlled trial provided an intervention based on the
      AIM-HI curriculum to 12 enhanced offices with support for office activities,
      while 12 traditional offices received only AIM-HI tools with encouragement for
      use with patients. Before intervention, at 4 months, and at 14 months, we
      measured the practice personnel's dietary behavior (PrimeScreen), physical
      activity (International Physical Activity Questionnaire), self-determined
      (intrinsic) motivation (Treatment Self-Regulation Questionnaire [TSRQ]),
      perceived ability to carry out health behaviors (Perceived Competence Scale), and
      readiness to improve and/or maintain health behaviors (Stages of Change).
      RESULTS: From 24 practices we enrolled 470 subjects; 21 practices completed the
      study, and data from 341 patients were analyzed. Differential change from
      baseline between the enhanced and traditional offices was not evident for
      behavior changes. An overall decrease from baseline in self-reported total
      physical activity measured as metabolic equivalent-minutes for all surveyed
      groups occurred over the study time period (4-month beta = -11.97; 14-month beta
      = -9.01; P = .003). A statistically significant increase occurred at 4 months
      among participants from the enhanced practices for the TSRQ outcomes of Healthy
      Eating (baseline, 3.00 +/- 0.12; 4 months, 3.26 +/- 0.13; P = .013). Among
      clinicians, TSRQ Healthy Eating scores increased from 3.19 +/- 0.13 at baseline
      to 3.52 +/- 0.14 at 4 months (P = .005). However, increases in TSRQ Eating scores
      were not sustained by 14 months. Stages of Change scores decreased from baseline
      to 4 months in enhanced group offices. There was also a decrease in Stages of
      Change scores among staff from baseline to 14 months. CONCLUSIONS: Primary care
      clinicians and office staff are resistant to health behavior change. External
      motivation did not seem to help them change. The effect of this intervention on
      patient care is not yet known.

PMID- 22956704
TI  - Are pediatric quality care measures too stringent?
AB  - INTRODUCTION: We aimed to demonstrate the application of national pediatric
      quality measures, derived from claims-based data, for use with electronic medical
      record data, and determine the extent to which rates differ if specifications
      were modified to allow for flexibility in measuring receipt of care. METHODS: We
      reviewed electronic medical record data for all patients up to 15 years of age
      with >=1 office visit to a safety net family medicine clinic in 2010 (n = 1544).
      We assessed rates of appropriate well-child visits, immunizations, and body mass
      index (BMI) documentation, defined strictly by national guidelines versus by
      guidelines with clinically relevant modifications. RESULTS: Among children aged
      <3 years, 52.4% attended >=6 well-child visits by the age of 15 months; 60.8% had
      >=6 visits by age 2 years. Less than 10% completed 10 vaccination series before
      their second birthday; with modifications, 36% were up to date. Among children
      aged 3 to 15 years, 63% had a BMI percentile recorded; 91% had BMI recorded
      within 36 months of the measurement year. CONCLUSIONS: Applying relevant
      modifications to national quality measure definitions captured a substantial
      number of additional services. Strict adherence to measure definitions might miss
      the true quality of care provided, especially among populations that may have
      sporadic patterns of care utilization.

PMID- 22956706
TI  - Improving multiple health risk behaviors in primary care: lessons from the
      Prescription for Health Common Measures, Better Outcomes (COMBO) study.
AB  - BACKGROUND: Four health behaviors--smoking, risky drinking, physical inactivity,
      and unhealthy diets--contribute substantially to health care burden and are
      common among primary care patients. However, there is insufficient evidence to
      recommend broadly brief interventions to address all 4 of these in frontline
      primary care. This study took advantage of a multinetwork initiative to reflect
      on health behavior outcomes and the challenges of using a common set of measures
      to assess health behavior-change strategies for multiple health behaviors in
      routine primary care practice. METHODS: Standardized, brief practical health
      behavior and quality of life measures used across 7 practice-based research
      networks (PBRNs) with independent primary care interventions in 54 primary care
      practices between August 2005 and December 2007 were analyzed. Mixed-effects
      longitudinal models assessed whether intervention patients improved diet,
      physical activity, smoking, alcohol consumption, and unhealthy days over time.
      Separate analyses were conducted for each intervention. RESULTS: Of 4463 adults,
      2199 had follow-up data, and all available data were used in longitudinal
      analyses. Adjusting for age, race/ethnicity, education, and baseline body mass
      index where available, diet scores improved significantly in 5 of 7 networks (P <
      .02). Physical activity improved significantly in 2 networks but declined in one
      network (P < .024). The likelihood of being a current smoker was reduced in 2 of
      5 networks (P < .0001), and average alcoholic drinks per day was reduced in 2
      networks (P < .02). Participants reported fewer unhealthy days at follow-up in 3
      of 7 networks (P < .01). Details of implementation and the limitations in
      instrumentation help contextualize these modest outcomes. CONCLUSIONS: Although
      some patients in these 7 PBRNs improved in several health behaviors and quality
      of life, the strength of evidence for field-ready methods to address multiple
      health risk behaviors remains elusive. The use of common measures to assess
      changes in 4 unhealthy behaviors was achieved practically in PBRNs testing
      diverse strategies to improve behaviors; however, variations in implementation,
      instrumentation performance, and some features of study design overwhelmed
      potential cross-PBRN comparisons. For common measures to be useful for
      comparisons across practices or PBRNs, greater standardization of study designs
      and careful attention to practicable implementation strategies are necessary.

PMID- 22956708
TI  - Growth and changes in the National Health Service Corps (NHSC) workforce with the
      American Recovery and Reinvestment Act.
AB  - BACKGROUND: From March 2009 through February 2011, the National Health Service
      Corps (NHSC) received a $300 million supplement through the American Recovery and
      Reinvestment Act to grant more loan repayment awards to clinicians who agree to
      work in underserved areas. This study assesses how this unprecedented funding
      increase affected the size, composition, and location of the NHSC's workforce.
      METHODS: This was a descriptive, time-linked, observational study using NHSC
      administrative data. Main outcomes were growth and changes in disciplinary
      composition of the NHSC's workforce and in its rural/urban and state-to-state
      distribution. RESULTS: During the Recovery Act period, the NHSC's workforce
      increased by 156%, from 3017 to 7713 clinicians. Mental health clinicians grew
      most numerically (210%) and as a proportion of the NHSC's workforce (from 22.7%
      to 27.4%). Primary care clinicians grew least and decreased as a proportion of
      the NHSC's workforce to 58.9%; dental health clinicians remained steady at
      approximately 13.5%. Among individual disciplines, physicians decreased most as a
      component of the NHSC's overall workforce, from 38.6% to 26.7%, whereas the
      proportion of nurse practitioners grew most, from 10.1% to 16.0%. Proportions of
      the NHSC's workforce serving in rural areas changed only modestly. NHSC clinician
      numbers grew most in states with the lowest NHSC clinician-to-poverty population
      ratios before the Recovery Act. CONCLUSIONS: With Recovery Act funding, the
      NHSC's workforce become far larger and more diverse than ever and more evenly
      distributed across states. The NHSC should now set targets and be more deliberate
      in managing its growth across disciplines and where its clinicians serve.

PMID- 22956707
TI  - A randomized controlled trial of a tailored primary care program to reverse
      excessive alcohol consumption.
AB  - OBJECTIVES: To assess the effects of a tailored, multifaceted intervention in
      primary care on the level of patients' alcohol consumption and to investigate
      which patient and organizational factors determine a reduction in alcohol
      consumption. METHODS: This was a cluster randomized, controlled trial conducted
      among primary care practices in The Netherlands. Data from 6318 patients were
      available, of whom 712 patients from 70 practices were hazardous or harmful
      alcohol users. The improvement (intervention) program combined professional,
      organizational, and patient-directed activities. The emphasis was on educational
      training for general practitioners and support visits by a trained facilitator,
      tailored to the participants' needs and attitudes. The primary outcome was the
      proportion of patients with hazardous or harmful alcohol consumption, as measured
      with the Alcohol Use Disorders Identification Test, who reduced their levels of
      alcohol consumption to low-risk levels after 2 years. RESULTS: Of the hazardous
      and harmful alcohol users, a substantial proportion (41.6%) reduced their alcohol
      consumption to a low-risk level. The trial revealed a significant difference in
      favor of the control group: 35.5% of the patients with hazardous and harmful
      alcohol consumption in general practitioners' practices in the intervention group
      and 47.0% of this patient group in general practitioners' practices in the
      control group reduced their alcohol consumption to a low-risk level (odds ratio
      [OR], 0.62; 95% confidence interval [CI], 0.43-0.90). Older age (OR, 1.02; 95%
      CI, 1.01-1.03), female sex (OR, 2.00; 95% CI, 1.26-3.19), and attitudes toward
      alcohol use seemed to be the most important predictors for the reduction of
      alcohol use to a low-risk level. Patients who considered it important to reduce
      alcohol consumption and patients who believed that less alcohol complicates
      relaxation were less likely to reduce their alcohol use to a low-risk level (OR,
      0.39; 95% CI, 0.19-0.80 and OR, 0.58; 95% CI, 0.37-0.90, respectively).
      Characteristics of the general practices, however, were not associated with
      reduced alcohol use. CONCLUSIONS: Our results suggest that the intervention has
      been counterproductive because the proportion of patients reducing their levels
      of alcohol consumption to low-risk levels was lower in the intervention group
      compared with the control group. Furthermore, our study demonstrated that
      patients' attitudes toward alcohol use are an important determinant of the
      success of the program. Therefore, future research should focus on the
      effectiveness of methods to change patients' attitudes.

PMID- 22956709
TI  - Soil-related bacterial and fungal infections.
AB  - A variety of classic and emerging soil-related bacterial and fungal pathogens
      cause serious human disease that frequently presents in primary care settings.
      Typically, the growth of these microorganisms is favored by particular soil
      characteristics and may involve complex life cycles including amoebae or animal
      hosts. Specific evolved virulence factors or the ability to grow in diverse,
      sometimes harsh, microenvironments may promote pathogenesis. Infection may occur
      by direct inoculation or ingestion, ingestion of contaminated food, or
      inhalation. This narrative review describes the usual presentations and
      environmental sources of soil-related infections. In addition to tetanus,
      anthrax, and botulism, soil bacteria may cause gastrointestinal, wound, skin, and
      respiratory tract diseases. The systemic fungi are largely acquired via
      inhalation from contaminated soil and near-soil environments. These fungal
      infections are particularly life-threatening in those with compromised immune
      systems. Questions regarding soil exposure should be included in the history of
      any patient with syndromes consistent with tetanus, botulism or anthrax,
      traumatic wounds, recalcitrant skin lesions, gastroenteritis, and nonresponsive,
      overwhelming, or chronic pneumonia.

PMID- 22956710
TI  - A characteristic cognitive and behavioral pattern as a clue to suspect
      Klinefelter syndrome in prepubertal age.
AB  - Klinefelter syndrome (KS) with the classic 47,XXY karyotype is the most frequent
      chromosomal aneuploidy, with a prevalence of 1 in 700 men; although the classic
      clinical picture is well-known and easily recognizable, most patients remain
      undiagnosed. The rate of diagnosis during childhood is extremely low, and only
      10% of cases are identified before puberty, with a subsequent rate of
      ascertainment during lifetime of 25%. The low rate of timely diagnosis is because
      most of the classical signs and symptoms of androgen deficiency appear in mid- to
      late adolescence but it is important to recognize that adult men with KS may show
      a great variability in clinical and physical features. A common, often
      underappreciated, element in young boys and children with KS is the
      characteristic cognitive and behavioral pattern. We describe 2 patients who were
      diagnosed at 7.1 and 10 years through a characteristic neurocognitive profile.
      Both of them showed low-normal scores when evaluated by tests of general
      intelligence and a behavioral profile characterized by immaturity, low self
      esteem, and learning disabilities. Clinical examination showed tall stature and
      progressive growth acceleration between 5 and 7 years, and one of them had
      hypoplastic scrotum with monolateral cryptorchidism. To achieve the goal of an
      early diagnosis of KS, it is necessary to increase medical awareness of the
      disease and, in particular, to augment pediatricians' knowledge that during
      prepubertal age pathognomonic clinical features of KS are often lacking but a
      characteristic cognitive and behavioral pattern is commonly present.

PMID- 22956711
TI  - Comorbidity of Bipolar Disorder (BPD) and ADHD in Children and Adolescents:
      Studies Outside the United States, Methodological Issues Inflating Comorbidity,
      Role of Behavioural Sensitization, and Concept of Temper Dysregulation Disorder
      With Dysphoria Proposed by DSM-5 Work Group.

PMID- 22956712
TI  - Antibasal Ganglia Antibodies and Antistreptolysin O in Noncomorbid ADHD.
AB  - OBJECTIVE: An association between streptococcal infections, ABGA positivity, and
      no comorbidity ADHD (nc-ADHD) has been little investigated. The aim of this study
      was to evaluate the streptococcal infection frequency, defined entitled serum
      antistreptolysin O (ASO), and frequency of serum ABGA positivity in a sample of
      patients with nc-ADHD. METHOD: In all 40 participants were investigated the ASO
      titer and ABGA. RESULTS: The results showed that ABGA positivity was
      statistically significantly higher in patients affected by ADHD than in patients
      of a control group, and pathological values of ASO were statistically more
      frequent in the ADHD group than the control group. CONCLUSION: These data suggest
      that streptococcal infections and autoimmune reactions against the basal ganglia
      are more frequent in ADHD patients than patients in a control group.

PMID- 22956713
TI  - Attachment and autonomy problems in adults with ADHD.
AB  - OBJECTIVE: Attachment security and autonomy were examined in adults with ADHD.
      Insecure attachment and autonomy problems were expected to be negatively
      associated with general psychological functioning. METHOD: Questionnaires were
      administered (Relationship Questionnaire, Autonomy-Connectedness Scale, Brief
      Symptom Inventory) in 84 late-diagnosed adults with ADHD. RESULTS: Only 18% of
      participants were securely attached, as opposed to 59% in the normal population.
      Concerning autonomy, participants scored below average on self-awareness, above
      average on sensitivity to others, and average on capacity to manage new
      situations compared with the normal population. The preoccupiedly attached group
      reported more problems in psychological functioning than the secure and
      dismissive group. Sensitivity to others and capacity to manage new situations
      were associated with psychological functioning; self-awareness was not.
      Attachment security and autonomy contributed to general psychological
      functioning. CONCLUSION: Attachment and autonomy problems do exist in adults with
      ADHD and contribute negatively to their psychological functioning.

PMID- 22956714
TI  - The prevalence of ADHD: its diagnosis and treatment in four school districts
      across two states.
AB  - OBJECTIVE: To describe the epidemiology of ADHD in communities using a DSM-IVTR
      case definition. METHOD: This community-based study used multiple informants to
      develop and apply a DSM -IVTR-based case definition of ADHD to screening and
      diagnostic interview data collected for children 5-13 years of age. Teachers
      screened 10,427 children (66.4%) in four school districts across two states (SC
      and OK). ADHD ratings by teachers and parent reports of diagnosis and medication
      treatment were used to stratify children into high and low risk for ADHD. Parents
      (n = 855) of high risk and gender frequency-matched low risk children completed
      structured diagnostic interviews. The case definition was applied to generate
      community prevalence estimates, weighted to reflect the complex sampling design.
      RESULTS: ADHD prevalence was 8.7% in SC and 10.6% in OK. The prevalence of ADHD
      medication use was 10.1% (SC) and 7.4% (OK). Of those medicated, 39.5% (SC) and
      28.3% (OK) met the case definition. Comparison children taking medication had
      higher mean symptom counts than other comparison children. CONCLUSIONS: Our ADHD
      estimates are at the upper end of those from previous studies. The identification
      of a large proportion of comparison children taking ADHD medication suggests that
      our estimates may be conservative; these children were not included as cases in
      the case definition, although some might be effectively treated.

PMID- 22956715
TI  - Maternal postadoption depression, unmet expectations, and personality traits.
AB  - BACKGROUND: There are approximately 2 million adoptive parents in the United
      States and some struggle with depressive symptoms postplacement. We know little
      about personality traits that may be associated with depression in adoptive
      parents. OBJECTIVES: This study describes the relationships between personality
      traits, unmet expectations, and maternal postadoption depression. DESIGN:
      Adoptive mothers (N = 136) were surveyed for depressive symptoms using the Center
      for Epidemiologic Studies-Depression Scale (CES-D) and the Edinburgh Postnatal
      Depression Scale (EPDS). Analyses included correlations and a regression analysis
      between depressive symptoms and unmet expectations with the Five-Factor Model
      personality traits (extraversion, agreeableness, conscientiousness, emotional
      stability, openness to experience) as measured by the Ten-Item Personality
      Inventory. RESULTS: Both the CES-D and EPDS were significantly, negatively
      correlated with all five personality dimensions. Mothers whose expectations of
      themselves as parents matched pre- and postplacement were more likely to be
      emotionally stable and extraverted. Approximately 36% of the variance in
      depressive symptoms was explained by personality traits (emotional stability: p <
      .0001). CONCLUSIONS: The postadoption period is a crucial time of transition for
      mothers and their children. Maternal emotional stability, depressive symptoms,
      and unmet expectations may affect this period. Mothers who are lower in emotional
      stability may be at risk for postadoptive depressive symptoms. In planning and
      providing innovative care that promotes positive mother-child relationships,
      nurses should assess adoptive mothers for depressive symptoms, emotional
      stability, and unmet expectations.

PMID- 22956716
TI  - Massive neurocysticercosis: encephalitic versus non-encephalitic.

PMID- 22956717
TI  - The importance of the global health strategy from the U.S. Department of Health
      and Human Services.

PMID- 22956718
TI  - Does HIV/AIDS funding undermine health systems?

PMID- 22956721
TI  - Never tear us apart--the importance of centrosome clustering.
AB  - The presence of more than two centrosomes (centrosome amplification) at the onset
      of mitosis has long been associated with multipolar spindle formation, and with
      the generation of genetic instability. However, in recent years, several studies
      have shown that a process termed 'centrosome clustering' actively contributes to
      bipolar division by promoting the gathering of extra centrosomes in two main
      poles. In this Commentary, we describe the main proteins that are involved in
      centriole duplication and discuss how centrosome amplification can be generated
      both in vitro and in vivo. We then summarize what is currently known about the
      processes that contribute to bipolar spindle formation when extra centrosomes are
      present, and which forces contribute to this process. Finally, we discuss how
      extra centrosomes might contribute to tumorigenesis, giving emphasis to the role
      of centrosome amplification in promoting genetic instability.

PMID- 22956720
TI  - Neurofilaments at a glance.

PMID- 22956722
TI  - Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary
      deiodinase 2 activity.
AB  - Endogenous androgens are involved in regulation of thyroid function and
      metabolism of thyroid hormones. As serum testosterone level progressively
      declines with age, this regulation may change. We tested how androgen
      deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged
      rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated
      under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery,
      animals were decapitated. Thyroids were used for histomorphometric and
      ultrastructural examinations and together with livers and pituitaries for real
      time quantitative PCR and deiodinase (DIO) activity measurements. Serum
      testosterone, TSH, l-thyroxine (T(4)), and cholesterol (Chol) levels were
      determined. As expected, middle-aged control rats had lower (P<0.05) testosterone
      and T(4) compared with 3-month-old males. In the Orx middle-aged group, we
      detected diminished serum testosterone (P<0.05), no change in TSH and T(4)
      levels, and higher Chol level (P<0.05), in comparison with age-matched controls.
      Histomorphometric analysis of thyroid tissue revealed decreased relative volume
      densities of follicles and colloid (P<0.05). Relevant gene expressions and DIO1
      enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene
      expression and DIO1 activity were decreased (P<0.05) in comparison with the
      control values. Pituitary levels of TSHbeta, Dio1, and Dio2 mRNAs did not change,
      while DIO2 activity decreased (P<0.05). In conclusion, orchidectomy of middle
      aged rats affected thyroid structure with no effect on serum T(4) and TSH.
      However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate
      compensatory-adaptive changes in local T(3) production.

PMID- 22956723
TI  - Identification of human butyrylcholinesterase organophosphate-resistant variants
      through a novel mammalian enzyme functional screen.
AB  - Human butyrylcholinesterase (hBChE) is currently being developed as a
      detoxication enzyme for the catalytic hydrolysis or stoichiometric binding of
      organophosphates (OPs). Previously, rationally designed hBChE mutants (G117H and
      E197Q) were reported in the literature and showed the feasibility of engineering
      OP hydrolytic functional activity into hBChE. However, the OP hydrolysis rate for
      G117H is too low for clinical utility. Additional OP-resistant hBChE variants
      with greater hydrolysis rates are needed as OP nerve-agent countermeasures for
      therapeutic utility. As described herein, a directed molecular evolution process
      was used to identify amino acid residues that contribute to OP-resistant
      functional activity of hBChE variants. In this article, we describe the
      development and validation of a novel method to identify hBChE variants with OP
      resistant functional activity (decreased rate of OP inhibition). The method
      reported herein used an adenoviral protein expression system combined with a
      functional screening protocol of OP nerve-agent model compounds that have been
      shown to have functional properties similar to authentic OP nerve-agent
      compounds. The hBChE screening method was robust for transfection efficiency,
      library diversity, and reproducibility of positive signals. The screening
      approach not only identified the previously reported hBChE G117H variant, but
      also identified a series of additional hBChE variants, including hBChE G117N,
      G117R, E197C, and L125V, that exhibited OP-resistant functional activities not
      reported previously. The mammalian functional screening approach can serve as a
      cornerstone for further optimization and screening for OP-resistant hBChEs for
      potential therapeutic applications.

PMID- 22956725
TI  - The worldwide perspective on human papillomavirus and cervical cancer.

PMID- 22956726
TI  - Cervical cancer in Latin America and the Caribbean: the problem and the way to
      solutions.
AB  - Latin America and the Caribbean have one of the highest incidence and mortality
      rates from cervical cancer in the world. In this region, age-adjusted incidence
      rates range from 20 to 80 per 100,000 women per year. Overall, the mortality
      rates are extremely high in spite of the availability of Pap screening in several
      countries. Women from lower socioeconomic status, often less educated, are
      unaware of cervical cancer screening or have no access to it. Despite the efforts
      to reorganize screening programs in the region, in a few countries, only a slight
      decrease in cervical cancer mortality has been observed. New modalities for
      primary and secondary screening should be evaluated and disseminated, including
      HPV testing and vaccination against the most common HPV types. HPV prophylactic
      vaccines were approved in most Latin American countries, but only few are
      considering its implementation in national immunization programs. Besides cost
      and other logistical issues, lack of recommendation by policy makers or lawmakers
      is deterring the introduction of HPV vaccines in the region. Furthermore, studies
      conducted in the region have indicated that HPV vaccination only or vaccination
      supplemented with screening may be considered a cost-effective strategy to reduce
      mortality by cervical cancer.

PMID- 22956727
TI  - Cervical cancer burden and prevention strategies: Asia Oceania perspective.
AB  - The Asia Oceania region contributes to more than 50% of cervical cancer cases
      worldwide. Yet cervical cancer is one of few cancers that can be prevented
      through comprehensive screening for precancerous lesions, with their subsequent
      treatment. Screening with cervical cytology, a very old technology, has reduced
      cervical cancer mortality and incidence when applied in comprehensive programs
      with high coverage and high quality assurance. However, of those countries within
      this region that have set up such programs, many have been opportunistic, had
      poor coverage, or inadequate treatment facilities for lesions found.
      Consequently, they have not seen large reductions in cancer incidence or
      mortality. Some have therefore adopted visual inspection by acetic acid (VIA) and
      Lugol's iodine (VILI) or human papillomavirus (HPV) DNA assays for screening.
      With two safe, immunogenic and efficacious prophylactic vaccines licensed, the
      way forward to reduction of cervical cancer to becoming uncommon is within reach.
      Where governments have supported high coverage public-health vaccination
      programs, reductions in disease burden with shortest incubation (genital warts,
      high-grade abnormalities) are already being reported. One of the biggest
      impediments is the cost of vaccines that are affordable to resource-poor
      countries. Other challenges include, infrastructure for delivery of vaccines,
      plus general acceptance of vaccination by the community.

PMID- 22956728
TI  - Cervical cancer burden and prevention activities in Europe.
AB  - Cervical cancer is an important public health care problem in Europe. The overall
      incidence rate of cervical cancer in Europe is 10.6 per 100,000. However, within
      Europe, the incidence rates significantly differ, being lower in Western Europe
      where prevention programs are better developed. Significantly higher are the
      incidence and mortality rates in Central and Eastern Europe, being in close
      correlation to the intensity of organized screening. Human papillomavirus (HPV)
      vaccines are being delivered to the low-incidence populations that already have
      extensive screening programs, whereas the high-incidence countries have not
      implemented the vaccination programs yet. The resolution of the problem of
      cervical cancer control in Europe will be a matter of the implementation of
      public health care programs across the whole continent.

PMID- 22956729
TI  - Aspirin and cancer prevention and treatment: are we there yet?

PMID- 22956730
TI  - Mammographic screening and breast cancer mortality: a case-control study and meta
      analysis.
AB  - BACKGROUND: Observational studies are necessary to assess the impact of
      population screening on breast cancer mortality. While some ecological studies
      have notably found little or no association, case-control studies consistently
      show strong inverse associations, but they are sometimes ignored, perhaps due to
      theoretical biases arising from the study design. We conducted a case-control
      study of breast cancer deaths in Western Australia to evaluate the effect of
      participation in the BreastScreen Australia program, paying particular attention
      to potential sources of bias, and undertook an updated meta-analysis of case
      control studies. METHODS: Our study included 427 cases (women who died from
      breast cancer), each matched to up to 10 controls. We estimated the association
      between screening participation and breast cancer mortality, quantifying the
      effect of potential sources of bias on our findings, including selection bias,
      information bias, and confounding. We also conducted a meta-analysis of published
      case-control studies. RESULTS: The OR for participation in the Western Australian
      BreastScreen program in relation to death from breast cancer was 0.48 [95%
      confidence interval (CI), 0.38-0.59; P < 0.001]. We were unable to identify
      biases that could negate this finding: sensitivity analyses generated ORs from
      0.45 to 0.52. Our meta-analysis yielded an OR of 0.51 (95% CI, 0.46-0.55).
      CONCLUSIONS: Our findings suggest an average 49% reduction in breast cancer
      mortality for women who are screened. In practice, theoretical biases have little
      effect on estimates from case-control studies. IMPACT: Case-control studies, such
      as ours, provide robust and consistent evidence that screening benefits women who
      choose to be screened.

PMID- 22956731
TI  - File formats commonly used in mass spectrometry proteomics.
AB  - The application of mass spectrometry (MS) to the analysis of proteomes has
      enabled the high-throughput identification and abundance measurement of hundreds
      to thousands of proteins per experiment. However, the formidable informatics
      challenge associated with analyzing MS data has required a wide variety of data
      file formats to encode the complex data types associated with MS workflows. These
      formats encompass the encoding of input instruction for instruments, output
      products of the instruments, and several levels of information and results used
      by and produced by the informatics analysis tools. A brief overview of the most
      common file formats in use today is presented here, along with a discussion of
      related topics.

PMID- 22956732
TI  - Functional proteomic analysis of long-term growth factor stimulation and receptor
      tyrosine kinase coactivation in Swiss 3T3 fibroblasts.
AB  - In Swiss 3T3 fibroblasts, long-term stimulation with PDGF, but not insulin-like
      growth factor 1 (IGF-1) or EGF, results in the establishment of an elongated
      migratory phenotype, characterized by the formation of retractile dendritic
      protrusions and absence of actin stress fibers and focal adhesion complexes. To
      identify receptor tyrosine kinase-specific reorganization of the Swiss 3T3
      proteome during phenotypic differentiation, we compared changes in the pattern of
      protein synthesis and phosphorylation during long-term exposure to PDGF, IGF-1,
      EGF, and their combinations using 2DE-based proteomics after (35)S- and (33)P
      metabolic labeling. One hundred and five differentially regulated proteins were
      identified by mass spectrometry and some of these extensively validated. PDGF
      stimulation produced the highest overall rate of protein synthesis at any given
      time and induced the most sustained phospho-signaling. Simultaneous activation
      with two or three of the growth factors revealed both synergistic and
      antagonistic effects on protein synthesis and expression levels with PDGF showing
      dominance over both IGF-1 and EGF in generating distinct proteome compositions.
      Using signaling pathway inhibitors, PI3K was identified as an early site for
      signal diversification, with sustained activity of the PI3K/AKT pathway critical
      for regulating late protein synthesis and phosphorylation of target proteins and
      required for maintaining the PDGF-dependent motile phenotype. Several proteins
      were identified with novel PI3K/Akt-dependent synthesis and phosphorylations
      including eEF2, PRS7, RACK-1, acidic calponin, NAP1L1, Hsp73, and fascin. The
      data also reveal induction/suppression of key F-actin and actomyosin regulators
      and chaperonins that enable PDGFR to direct the assembly of a motile
      cytoskeleton, despite simultaneous antagonistic signaling activities. Together,
      the study demonstrates that long-term exposure to different growth factors
      results in receptor tyrosine kinase-specific regulation of relatively small
      subproteomes, and implies that the strength and longevity of receptor tyrosine
      kinase-specific signals are critical in defining the composition and functional
      activity of the resulting proteome.

PMID- 22956733
TI  - Quantification of heterosubtypic immunity between avian influenza subtypes H3N8
      and H4N6 in multiple avian host species.
AB  - Low-pathogenicity avian influenza virus (LPAIV) can lead to epizootics that cause
      economic losses in poultry or the emergence of human-infectious strains. LPAIVs
      experience a complex immunity landscape as they are endemic in numerous host
      species, and many antigenically distinct strains co-circulate. Prevention and
      control of emergence of detrimental strains requires an understanding of
      infection/transmission characteristics of the various subtypes in different
      hosts, including interactions between subtypes. In order to develop analytical
      frameworks for examining control efficacy, quantification of heterosubtypic
      immunity interactions is fundamental. However, these data are scarce, especially
      for wild avian subtypes in natural hosts. Consequently, in this study, three host
      species (mallards, quail and pheasants) were infected with two LPAIV subtypes
      isolated from wild birds: H3N8 and H4N6. The recovered hosts were also reinfected
      with the alternate subtype to measure the effects of heterosubtypic immunity.
      Oropharyngeal and cloacal swabs were collected and viral RNA load was quantified
      by real-time RT-PCR. For secondary infections in recovered hosts, peak viral load
      was up to four orders of magnitude lower and shedding length was up to 4 days
      shorter. However, both the magnitude and presence of heterosubtypic immunity
      varied across specific host species/subtype combinations. Using a mathematical
      model of virus replication, the variation in virus replication dynamics due to
      host individuals was quantified. It was found that accounting for individual
      heterogeneity is important for drawing accurate conclusions about treatment
      effects. These results are relevant for developing epidemiological models to
      inform control practices and for analysing virus replication data.

PMID- 22956734
TI  - Comparative analysis of the fusion efficiency elicited by the envelope
      glycoprotein V1-V5 regions derived from human immunodeficiency virus type 1
      transmitted perinatally.
AB  - Understanding the properties of viruses preferentially establishing infection
      during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is
      critical for the development of effective measures to prevent transmission. A
      previous study demonstrated that the newly transmitted viruses (in infants) of
      chronically infected mother-infant pairs (MIPs) were fitter in terms of growth,
      which was imparted by their envelope (Env) glycoprotein V1-V5 regions, than those
      in the corresponding chronically infected mothers. In order to investigate
      whether the higher fitness of transmitted viruses was conferred by their higher
      entry efficiency directed by the V1-V5 regions during perinatal transmission, the
      fusogenicity of Env containing V1-V5 regions derived from transmitted and non
      tranmsmitted viruses of five chronically infected MIPs and two acutely infected
      MIPs was analysed using two different cell-cell fusion assays. The results showed
      that, in one chronically infected MIP, a higher fusion efficiency was induced by
      the infant Env V1-V5 compared with that of the corresponding mother. Moreover,
      the V4-V5 regions played an important role in discriminating the transmitted and
      non-transmitted viruses in this pair. However, neither a consistent pattern nor
      significant differences in fusogenicity mediated by the V1-V5 regions between
      maternal and infant variants was observed in the other MIPs. This study suggests
      that there is no consistent and significant correlation between viral fitness
      selection and entry efficiency directed by the V1-V5 regions during perinatal
      transmission. Other factors such as the route and timing of transmission may also
      be involved.

PMID- 22956735
TI  - Antigenic diversity and cross-reactivity of avian influenza H5N1 viruses in Egypt
      between 2006 and 2011.
AB  - Influenza epidemics are a major health concern worldwide. Highly pathogenic avian
      influenza (HPAI) H5N1 viruses in Egypt have been subject to rapid genetic and
      antigenic changes since the first outbreak in February 2006 and have been endemic
      in poultry in Egypt since 2008. In this study, 33 H5N1 viruses isolated from
      avian hosts were antigenically analysed by using a panel of eight mAbs raised
      against the A/Viet Nam/1203/04 (H5N1; clade 1) and A/bar-headed goose/Qinghai
      lake/1A/05 (H5N1; clade 2.2) influenza viruses. Rats were immunized with
      inactivated whole-virus vaccine produced by reverse genetics with the
      haemagglutinin and neuraminidase genes of eight antigenically different HPAI H5N1
      virus isolates and six internal genes from A/Puerto Rico/8/1934 (PR8) to produce
      polyclonal antibodies. Cross-reactivity between the obtained polyclonal
      antibodies and the isolated viruses was assayed. Antigenic cartography of the
      isolated viruses showed that three antigenic clusters were defined based on
      haemagglutination inhibition (HI) analysis using mAbs and the majority of viruses
      isolated in 2010 and 2011 fell into two of these clusters. An antigenic map based
      on polyclonal rat antisera showed that all virus isolates fell within one
      extended cluster. Accordingly, continuous surveillance and antigenic
      characterization will help us determine which virus isolate(s) should be used in
      poultry vaccine preparation.

PMID- 22956736
TI  - Incorporation of GP64 into Helicoverpa armigera nucleopolyhedrovirus enhances
      virus infectivity in vivo and in vitro.
AB  - The envelope fusion proteins of baculoviruses, glycoprotein GP64 from group I
      nucleopolyhedrovirus (NPV) or the F protein from group II NPV and granulovirus,
      are essential for baculovirus morphogenesis and infectivity. The F protein is
      considered the ancestral baculovirus envelope fusion protein, while GP64 is a
      more recent evolutionary introduction into baculoviruses and exhibits higher
      fusogenic activity than the F protein. Each of the fusion proteins is required by
      the respective virus to spread infection within larval tissues. A recombinant
      Helicoverpa armigera NPV (HearNPV) expressing GP64 from Autographa californica
      multiple nucleopolyhedrovirus, vHaBac-gp64-egfp, was constructed, which still
      retained the native F protein, and its infectivity was assayed in vivo and in
      vitro. Analyses by one-step growth curve to determine viral titre and by
      quantitative PCR to determine viral DNA copy number showed that vHaBac-gp64-egfp
      was more infectious in vitro than the control, vHaBac-egfp. The polyhedrin gene
      (polh) was reintroduced into the recombinant viruses and bioassays showed that
      vHaBac-gp64-polh accelerated the mortality of infected larvae compared with the
      vHaBac-egfp-polh control, and the LC(50) (median lethal concentration) of vHaBac
      gp64-polh was reduced to approximately 20 % of that of vHaBac-egfp-polh.
      Therefore, incorporation of GP64 into HearNPV budded virions improved virus
      infectivity both in vivo and in vitro. The construction of this bivalent virus
      with a more efficient fusion protein could improve the use of baculoviruses in
      different areas such as gene therapy and biocontrol.

PMID- 22956737
TI  - Discovery of a novel Torque teno sus virus species: genetic characterization,
      epidemiological assessment and disease association.
AB  - The study describes a novel Torque teno sus virus (TTSuV) species, provisionally
      named Torque teno sus virus k2b (TTSuVk2b), originally found in commercial pig
      sera by applying the rolling-circle amplification technique. Full-length
      sequences of TTSuVk2b were obtained, annotated and used in the phylogenetic
      analyses, which revealed that TTSuVk2b is a novel Anellovirus species within the
      genus Kappatorquevirus of the family Anelloviridae. Quantitative PCR techniques
      were developed to determine total TTSuV DNA quantities as well as the prevalence
      and viral DNA quantities of TTSuV1, TTSuVk2a and TTSuVk2b. The mean total TTSuV
      load in seven commercial sera was determined at 6.3 log(10) DNA copies ml(-1) of
      serum, with TTSuVk2b loads being the lowest at 4.5 log(10) DNA copies ml(-1) of
      serum. Subsequently, prevalence and loads of TTSuVs were determined in pig sera
      from 17 countries. TTSuVk2b prevalence ranged from 0 to 100 % with viral loads
      from 3.3 to 4.6 log(10) copies ml(-1) of sera. TTSuVk2a, so far the only species
      in the genus Kappatorquevirus, has been linked to an economically important swine
      disease, namely post-weaning multisystemic wasting syndrome (PMWS). Considering
      the grouping of TTSuVk2b in the same genus as TTSuVk2a, TTSuVk2b prevalence and
      viral DNA load were determined in PMWS-affected animals and healthy counterparts.
      This revealed that TTSuVk2a and TTSuVk2b are not only genetically related, but
      also that their viral loads in serum are elevated in PMWS animals compared with
      those of healthy pen mates. In summary, the present work describes a novel TTSuV
      species including its genetic characterization, epidemiological assessment and
      potential disease association.

PMID- 22956739
TI  - Human dignity and rights beyond death.

PMID- 22956738
TI  - Combined action of type I and type III interferon restricts initial replication
      of severe acute respiratory syndrome coronavirus in the lung but fails to inhibit
      systemic virus spread.
AB  - STAT1-deficient mice are more susceptible to infection with severe acute
      respiratory syndrome coronavirus (SARS-CoV) than type I interferon (IFN) receptor
      deficient mice. We used mice lacking functional receptors for both type I and
      type III IFN (double knockout, dKO) to evaluate the possibility that type III IFN
      plays a decisive role in SARS-CoV protection. We found that viral peak titres in
      lungs of dKO and STAT1-deficient mice were similar, but significantly higher than
      in wild-type mice. The kinetics of viral clearance from the lung were also
      comparable in dKO and STAT1-deficient mice. Surprisingly, however, infected dKO
      mice remained healthy, whereas infected STAT1-deficient mice developed liver
      pathology and eventually succumbed to neurological disease. Our data suggest that
      the failure of STAT1-deficient mice to control initial SARS-CoV replication
      efficiently in the lung is due to impaired type I and type III IFN signalling,
      whereas the failure to control subsequent systemic viral spread is due to
      unrelated defects in STAT1-deficient mice.

PMID- 22956740
TI  - Misused honorary authorship is no excuse for quantifying the unquantifiable.
AB  - Kovacs argues that honorary authorship and regarding each co-author of multi
      authored papers as if they were sole authors when the performance of researchers
      is being evaluated by their publications mean that we should require authors to
      identify what proportion of each publication should be attributed to each co
      author. Even if such attributions could be made reliably, such a change should
      not be made. Contributions to authorship cannot be validly quantified, and the
      relative merits of different publications are also neither equal nor validly
      quantifiable. Research administrators need to recognise that whatever criteria
      they adopt to evaluate the performance of researchers, researchers will find a
      way to game the system in order to maximise their personal benefit. 

PMID- 22956741
TI  - Psychometric assessment of the croatian version of the breastfeeding self
      efficacy scale-short form.
AB  - BACKGROUND: Many mothers find it difficult to breastfeed exclusively for the
      recommended 6 months postpartum. The Breastfeeding Self-Efficacy Scale-Short Form
      (BSES-SF) was developed to measure breastfeeding self-efficacy, an important
      predictor of breastfeeding outcomes. OBJECTIVE: To translate and psychometrically
      assess the BSES-SF among women in Croatia. METHODS: A convenience sample of 190
      breastfeeding mothers was recruited from a Baby-Friendly hospital in Zagreb,
      Croatia. In-hospital mothers completed questionnaires that included the
      translated BSES-SF, Sense of Coherence Scale (SOC-13), and a demographic
      questionnaire. The follow-up questionnaires were administered to mothers at 1 and
      6 months postpartum to determine their infant feeding method. RESULTS: The mean
      total score of the Croatian version of the BSES-SF was 55 +/- 7. The Cronbach
      alpha coefficient for internal consistency was 0.86, suggesting good reliability.
      In-hospital BSES-SF scores significantly predicted breastfeeding duration and
      exclusivity at 1 and 6 months postpartum, providing support for predictive
      validity. The BSES-SF scores were significantly correlated with the total SOC
      scores (r = 0.32, P < .001) and the SOC subscales of comprehensibility (r = 0.35,
      P < .001), manageability (r = 0.26, P < .001), and meaningfulness (r = 0.20, P =
      .005), providing support for construct validity. CONCLUSION: This study provides
      evidence that the translated version of the BSES-SF may be a valid and reliable
      measure of breastfeeding self-efficacy among postpartum women in Croatia.

PMID- 22956743
TI  - Identifying breastfeeding-sensitive conditions by expert consensus.
AB  - BACKGROUND: Infant feeding-related health outcomes need to be consistently
      defined prior to inclusion in health services research. OBJECTIVE: To categorize
      conditions common in infants under 12 months old by their association with
      breastfeeding for use as outcome measures in a randomized, controlled trial of
      breastfeeding promotion. METHODS: A modified Delphi consensus method synthesized
      opinions of 13 physician experts on breastfeeding's association with ICD-9 infant
      diagnosis codes derived from literature review and medical center experience. A
      pilot round and 2 subsequent Delphi rounds were used. For the first round,
      consensus was achieved when more than 80% of experts agreed on a classification
      for a particular condition, with a predetermined level of certainty based on a 7
      point Likert scale. For the second round, consensus was achieved when a majority
      of experts agreed on the classification from Round 1. RESULTS: An initial 68
      diagnosis codes were identified for evaluation by the expert panel. After a pilot
      round, the codes were refined and condensed, which resulted in 38 diagnoses for
      categorization into 1 of 3 categories: (1) breastfeeding protects against the
      condition; (2) breastfeeding may cause or worsen the condition; and (3)
      breastfeeding is unrelated to the condition. At the conclusion of the process,
      consensus was achieved on the classification of 31 conditions, and 7 conditions
      remained unclassified because of a lack of consensus. CONCLUSIONS: This study
      provides a list of conditions common in infants under 12 months of age classified
      based on relationship to infant feeding method and validated by expert consensus.
      These conditions, based on readily available insurance claims data, contribute to
      the standardization of outcome measures used for health services research related
      to breastfeeding promotion.

PMID- 22956742
TI  - Mastitis is associated with IL-6 levels and milk fat globule size in breast milk.
AB  - BACKGROUND: From animal studies, it is known that mastitic inflammation of the
      mammary lobes can produce proinflammatory cytokines and can damage the milk fat
      globule (MFG). OBJECTIVE: To investigate, in women, whether MFG and interleukin
      (IL)-6 differences are observed between mastitic milk (MM) and healthy milk (HM)
      of a mother. METHODS: MM was obtained from the specific nipple pore leading to
      the mastitic lobe of 17 women; HM was obtained from the other breast. Milk
      sampling occurred at days 0 (pre-treatment), 1, and 2 (post-treatment). MFG size
      and IL-6 were measured by laser light scattering and enzyme-linked immunosorbent
      assay, respectively. We analyzed MFG and IL-6 differences between HM and MM,
      whether any differences occurred over time with treatment, and whether
      differences were observed between mothers with systemic symptoms (fever/malaise,
      Group A) or without systemic symptoms (Group B). RESULTS: On day 0, MM had higher
      MFG size (P < .01) and IL-6 levels (P < .001) than HM. This difference
      significantly decreased over time with treatment for both MFG size (P < .01) and
      IL-6 (P < .05). On day 0, Group A mothers had significantly larger MFG size (P <
      .01) and IL-6 (P < .001) than Group B. CONCLUSIONS: MM contains larger MFG and
      higher IL-6 levels than milk from the healthy breast. This difference is larger
      if accompanied by systemic symptoms of mastitis (fever/malaise). These changes
      decreased over time with treatment. Therefore, early initiation of appropriate
      treatment may be useful in limiting the processes that contribute to alterations
      in MFG size and IL-6.

PMID- 22956744
TI  - Mechanical ventilation after injury.
AB  - Injury is a major cause of critical illness worldwide. Severely injured patients
      often require mechanical ventilation not only to manage primary respiratory
      failure but also as adjunct to manage other conditions. Injury induces
      fundamental changes in multiple organ systems which directly impact ventilator
      management; these changes are not shared by patients without concomitant tissue
      injury. In this article, we review the physiologic changes after injury and
      discuss the impact of injury on ventilator strategies and management. We also
      explore the special considerations in patients with traumatic brain injury,
      thermal injury, blast injury or bronchopleural fistula. 

PMID- 22956745
TI  - Serological diagnosis of leptospiral uveitis by HbpA IgG ELISA.
AB  - Leptospirosis is a zoonotic disease that is highly prevalent in tropical
      countries; uveitis is one of the manifestations of leptospirosis. The leptospiral
      aetiology of uveitis is difficult to predict because of overlapping clinical
      symptoms with uveitis due to other causes. The objective of this study was to
      evaluate the leptospiral haemin-binding protein HbpA as a diagnostic antigen for
      the serodiagnosis of leptospiral uveitis. Serum samples from patients, clinically
      diagnosed with leptospiral uveitis, were tested by ELISA for anti-HbpA antibodies
      and compared against the 'gold standard' microscopic agglutination test (MAT).
      Non-leptospiral uveitis and normal healthy individuals were used as controls. A
      total of 60 serum samples from patients suffering from leptospiral uveitis were
      studied, obtained from Aravind Eye Hospital, Madurai. Anti-HbpA IgG antibodies
      were detected in 92 % of patients clinically diagnosed with leptospiral uveitis,
      indicating that it is more sensitive than MAT, which had a seropositivity of only
      50 %, and better than the commercially available Pan Bio IgM ELISA (81 %). The
      mean anti-HbpA antibody titre was significantly higher in leptospiral uveitis
      patients compared with controls (P<0.05). The antigen showed negligible cross
      reactivity with non-leptospiral uveitis samples and cataract controls. We
      conclude that HbpA IgG ELISA identified cases of uveitis with leptospirosis
      aetiology and proved to be useful in differentiating them from other forms of
      uveitis.

PMID- 22956746
TI  - Coxiella burnetii endocarditis after Q fever vaccination.
AB  - Coxiella burnetii is the causative bacterium of Q fever, a vaccine-preventable
      infection. C. burnetii is an unusual cause of culture-negative endocarditis.
      Here, we present a case of Q fever native valve endocarditis that developed in a
      young man despite prior vaccination. Definitive diagnosis was difficult and
      required C. burnetii-specific PCR testing.

PMID- 22956747
TI  - Extracts of Artemisia annua leaves and seeds mediate programmed cell death in
      Leishmania donovani.
AB  - Leishmaniasis is one of the major tropical parasitic diseases, and the condition
      ranges in severity from self-healing cutaneous lesions to fatal visceral
      manifestations. There is no vaccine available against visceral leishmaniasis (VL)
      (also known as kala-azar in India), and current antileishmanial drugs face major
      drawbacks, including drug resistance, variable efficacy, toxicity and parenteral
      administration. We report here that n-hexane fractions of Artemisia annua leaves
      (AAL) and seeds (AAS) possess significant antileishmanial activity against
      Leishmania donovani promastigotes, with GI(50) of 14.4 and 14.6 ug ml(-1),
      respectively, and the IC(50) against intracellular amastigotes was found to be
      6.6 and 5.05 ug ml(-1), respectively. Changes in the morphology of promastigotes
      and growth reversibility analysis following treatment confirmed the
      leishmanicidal effect of the active fractions, which presented no cytotoxic
      effect on mammalian cells. The antileishmanial activity was mediated via
      apoptosis, as evidenced by externalization of phosphatidylserine, in situ
      labelling of DNA fragments by terminal deoxynucleotidyltransferase-mediated dUTP
      nick end labelling (TUNEL) and cell-cycle arrest at the sub-G(0)/G(1) phase. High
      performance thin-layer chromatography (HPTLC) fingerprinting showed that the
      content of artemisinin in crude bioactive extracts (~1.4 ug per 100 ug n-hexane
      fraction) was too low to account for the observed antileishmanial activity.
      Characterization of the active constituents by GC-MS showed that alpha-amyrinyl
      acetate, beta-amyrine and derivatives of artemisinin were the major constituents
      in AAL and cetin, EINECS 211-126-2 and artemisinin derivatives in AAS. Our
      findings indicate the presence of antileishmanial compounds besides artemisinin
      in the n-hexane fractions of A. annua leaves and seeds.

PMID- 22956748
TI  - Prevalence and antifungal susceptibility of Candida parapsilosis complex isolates
      collected from oral cavities of HIV-infected individuals.
AB  - At present, few data are available on the prevalence and antifungal
      susceptibility of Candida parapsilosis complex isolates from HIV-infected
      individuals. The C. parapsilosis complex comprises three species, C. parapsilosis
      sensu stricto, C. metapsilosis and C. orthopsilosis. Fifteen of 318 Candida
      isolates were identified as members of the C. parapsilosis complex by PCR and
      restriction fragment length polymorphism (RFLP). The prevalence of C.
      parapsilosis complex isolates was 4.7 %, 2.2 % being identified as C.
      parapsilosis sensu stricto and 2.5 % as C. metapsilosis, while no C.
      orthopsilosis was isolated. This is believed to be the first study that has
      identified isolates of C. metapsilosis obtained from the oral cavity of HIV
      infected individuals. Antifungal susceptibility tests indicated that all the
      isolates were susceptible to amphotericin B (AMB), fluconazole (FLC),
      ketoconazole (KTC), itraconazole (ITC), voriconazole (VRC) and caspofungin
      (CASPO). Although isolates of C. parapsilosis sensu stricto and C. metapsilosis
      were susceptible to FLC, isolates of C. metapsilosis showed a tendency for higher
      MICs (>=1.0 ug ml(-1)). Based upon the frequency of candidiasis and the fact that
      certain isolates of the C. parapsilosis complex respond differently to FLC
      therapy, our data may be of therapeutic relevance with respect to susceptibility
      and potential resistance to specific antifungal agents. Our data suggest that C.
      metapsilosis can be a human commensal; its importance as a pathogen has yet to be
      confirmed.

PMID- 22956749
TI  - Trichosporon asahii causing nosocomial urinary tract infections in intensive care
      unit patients: genotypes, virulence factors and antifungal susceptibility
      testing.
AB  - Trichosporon asahii is the causative agent of both superficial and deep-seated
      infections of increasing morbidity and mortality. Urinary tract infections (UTIs)
      due to T. asahii, frequently associated with indwelling medical devices, have
      been reported over the years. However, few studies have specifically focused on
      the genotypic diversity of T. asahii isolates from urine specimens from intensive
      care units (ICUs), let alone potential virulence factors and antifungal
      susceptibility testing. In the present study, 23 T. asahii isolates were
      collected from UTI patients in ICUs between January 2008 and January 2012. Three
      genotypes (I, III, IV) were determined based on the combination of internal
      transcribed spacer and intergenic spacer locus PCR. Protease, phospholipase and
      haemolysin production was assessed by halo formation on corresponding agar
      plates. Only haemolytic activity was observed to varying degrees. Neither
      protease nor phospholipase was detectable. Biofilm formation on polystyrene
      surfaces was detected through a formazan salt reduction assay. All clinical
      isolates had the ability to form biofilm. In contrast to the susceptibility of
      planktonic T. asahii cells to clinically used amphotericin B, 5-flucytosine,
      fluconazole, itraconazole and voriconazole, a remarkable rise in the MICs of
      these for biofilm T. asahii cells was observed. Our results suggested that
      genotype IV was the most prevalent genotype among T. asahii isolates from ICUs in
      China. Haemolysin and biofilm might contribute to the pathogenicity and
      recurrence of T. asahii-related UTIs. Although triazoles, especially
      voriconazole, were effective against planktonic T. asahii cells, they failed to
      treat preformed biofilms.

PMID- 22956750
TI  - Differential adhesion and invasion by Staphylococcus aureus of epithelial cells
      derived from different anatomical sites.
AB  - Staphylococcus aureus can invade epithelial cells, and the host-cell receptor
      alpha(5)beta(1) integrin is thought to mediate this process. The aim of this
      study was to investigate S. aureus invasion of epithelial cell lines derived from
      oral (H357), skin (UP) and nasopharyngeal (Detroit 562) sites and to determine
      whether any differences were due to the levels of alpha(5)beta(1) integrin
      expressed. While the adhesion and invasion of two S. aureus strains were similar
      in both oral and skin-derived keratinocytes, this was markedly reduced in the
      nasopharyngeal cell line, despite it expressing similar levels of
      alpha(5)beta(1). While this might be explainable on the basis of availability of
      cell receptor, adhesion to and invasion of H357 and UP cells by S. aureus were
      enhanced when the epithelial cells were in suspension rather than on a surface,
      and levels of alpha(5) integrin subunit mRNA were also increased. Detroit 562
      cells exhibited a similar alpha(5) gene upregulation, but this did not result in
      enhanced adhesion and invasion of S. aureus. The Detroit 562 cells also showed
      reduced adhesion to fibronectin compared with the other cell types. This, and the
      low S. aureus invasion, may result from reduced alpha(5)beta(1) integrin activity
      or from variation in an as-yet-unidentified additional receptor or accessory
      molecule. These studies shed further light on the mechanisms of S. aureus
      invasion of human cells.

PMID- 22956751
TI  - Does interferon-sparing tenofovir disoproxil fumarate-based therapy have a role
      in the management of severe acute hepatitis delta superinfection?
AB  - Infection with hepatitis delta virus (HDV) always occurs in association with
      hepatitis B virus (HBV) and is a cause of significant morbidity and mortality. We
      present a case of severe acute HDV infection superimposed on a previously
      unrecognized HBV infection, in which an interferon-sparing antiviral therapy
      consisting of tenofovir disoproxil fumarate (TDF) and lamivudine was initiated
      and subsequently maintained. Evidence of successful suppression of HDV
      ribonucleic acid (RNA) was obtained after 65 weeks of TDF-based treatment. This
      was mirrored by a significant reduction in the levels of HBV DNA and HBV surface
      antigen. HDV RNA subsequently rebounded after our patient stopped antiviral
      therapy of his own accord. Interferon-sparing TDF-based antiviral therapy was
      safe and effective in achieving HDV RNA suppression in acute HDV superinfection.
      Further research into the utility of interferon-sparing TDF-based regimes in the
      treatment of acute HDV infection is needed.

PMID- 22956752
TI  - Modified DNase tube test to detect DNase activity in Stenotrophomonas
      maltophilia.

PMID- 22956753
TI  - Synergistic effects between silver nanoparticles and antibiotics and the
      mechanisms involved.
AB  - Silver nanoparticles (nano-Ags), which have well-known antimicrobial properties,
      are used extensively in various medical and general applications. In this study,
      the combination effects between nano-Ags and the conventional antibiotics
      ampicillin, chloramphenicol and kanamycin against various pathogenic bacteria
      were investigated. The MIC and fractional inhibitory concentration index (FICI)
      were determined to confirm antibacterial susceptibility and synergistic effects.
      The results showed that nano-Ags possessed antibacterial effects and synergistic
      activities. The antibiofilm activities of nano-Ags alone or in combination with
      antibiotics were also investigated. Formation of biofilm is associated with
      resistance to antimicrobial agents and chronic bacterial infections. The results
      indicated that nano-Ags also had antibiofilm activities. To understand these
      effects of nano-Ags, an ATPase inhibitor assay, permeability assay and hydroxyl
      radical assay were conducted. The antibacterial activity of nano-Ags was
      influenced by ATP-associated metabolism rather than by the permeability of the
      outer membrane. Additionally, nano-Ags generated hydroxyl radicals, a highly
      reactive oxygen species induced by bactericidal agents. It was concluded that
      nano-Ags have potential as a combination therapeutic agent for the treatment of
      infectious diseases by bacteria.

PMID- 22956754
TI  - Multidrug-resistant Bacteroides fragilis group on the rise in Europe?
AB  - We report a case of multidrug-resistance (MDR) in a strain of Bacteroides
      fragilis from a blood culture and abdominal fluid in a Danish patient. The
      patient had not been travelling for several years and had not received
      antibiotics prior to the present case. We also summarize the cases that have been
      reported to date of MDR B. fragilis group in Europe. As far as we know, a case
      like this with MDR B. fragilis has not been described in Scandinavia before.

PMID- 22956755
TI  - Human adenovirus type 8 genome typing.
AB  - Human adenovirus type 8 (HAdV-8) is a major causative agent of epidemic
      keratoconjunctivitis, which is frequently associated with community, industrial
      and nosocomial outbreaks. Restriction endonuclease (RE) analysis discriminates
      HAdV-8 isolates into genome types, making it possible to correlate between
      genomic variants, virulence and outbreak potential. RE analysis is performed
      using two sets of classification criteria, an Asian and a European system. So
      far, genome types HAdV-8A-8K and HAdV-8/D1-D12 have been included in the Asian
      and European classifications, respectively. Conventionally followed RE analysis
      has some inherent problems, such as the use of a neutralization test for HAdV-8
      typing, which may misidentify some recombinant adenoviruses as HAdV-8 due to
      cross-reaction, the lack of a complete restriction profile for all genome types
      for purposes of comparison, and the absence of enzyme codes in the Asian
      classification system. In this review, we propose typing of HAdV-8 with
      phylogenetic analysis of the hexon and fibre genes prior to RE analysis due to
      the emergence of many recombinant types. Schematic restriction profiles for both
      classification systems were created by compiling all the published reports on
      genome types, and enzyme codes were included for the Asian classification system.
      The updated and simplified stepwise approach for HAdV-8 genome typing presented
      here could be useful for identifying either existing genome types or novel ones.

PMID- 22956756
TI  - Deletion of SenX3-RegX3, a key two-component regulatory system of Mycobacterium
      smegmatis, results in growth defects under phosphate-limiting conditions.
AB  - Two component regulatory systems are key elements in the control of bacterial
      gene expression in response to environmental perturbations. The SenX3-RegX3
      system is implicated in the control of phosphate uptake in Mycobacterium
      smegmatis and Mycobacterium tuberculosis. regX3 is reported to be essential in M.
      smegmatis, but not in M. tuberculosis. We attempted to construct complete senX3
      regX3 operon deletion strains of M. smegmatis; initially we found that the operon
      could only be deleted when another functional copy was provided. Using a strain
      in which the only functional copy of the operon was present on an integrating
      plasmid, we attempted to replace the functional copy with an empty vector.
      Surprisingly, we obtained strains in which the functional copy had been deleted
      from the chromosome at a low frequency. We deleted the senX3 gene in a similar
      fashion, but it was not possible to delete regX3 alone. To identify possible
      compensatory mutations we sequenced the whole genome of two deletion strains and
      the wild-type. A synonymous single nucleotide polymorphism (SNP) in a lipoprotein
      was found in all deletion strains, but not the parental strains, and a frameshift
      mutation in nhaA was identified in three of the four deletion strains. Operon
      deletion strains were more sensitive to phosphate limitation, showing a reduced
      ability to grow at lower phosphate concentrations. The M. tuberculosis operon was
      able to functionally complement the growth phenotype in M. smegmatis under
      phosphate-replete conditions, but not under low phosphate conditions, reinforcing
      the difference between the two species. Our data show that, in contrast with
      previous reports, it is possible to delete the operon in M. smegmatis, possibly
      due to the accumulation of compensatory mutations, and that the deletion does
      affect growth in phosphate.

PMID- 22956757
TI  - Toxicity of bovicin HC5 against mammalian cell lines and the role of cholesterol
      in bacteriocin activity.
AB  - Bacteriocins are ribosomally synthesized antimicrobial peptides produced by
      Bacteria and some Archaea. The assessment of the toxic potential of antimicrobial
      peptides is important in order to apply these peptides on an industrial scale.
      The aim of the present study was to investigate the in vitro cytotoxic and
      haemolytic potential of bovicin HC5, as well as to determine whether cholesterol
      influences bacteriocin activity on model membranes. Nisin, for which the
      mechanism of action is well described, was used as a reference peptide in our
      assays. The viability of three distinct eukaryotic cell lines treated with
      bovicin HC5 or nisin was analysed by using the MTT assay and cellular
      morphological changes were determined by light microscopy. The haemolytic
      potential was evaluated by using the haemoglobin liberation assay and the role of
      cholesterol on bacteriocin activity was examined by using model membranes
      composed of DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) and DPoPC (1,2
      dipalmitoyl-sn-glycero-3-phosphocholine). The IC(50) of bovicin HC5 and nisin
      against Vero cells was 65.42 and 13.48 uM, respectively. When the MTT assay was
      performed with MCF-7 and HepG2 cells, the IC(50) obtained for bovicin HC5 was
      279.39 and 289.30 uM, respectively, while for nisin these values were 105.46 and
      112.25 uM. The haemolytic activity of bovicin HC5 against eukaryotic cells was
      always lower than that determined for nisin. The presence of cholesterol did not
      influence the activity of either bacteriocin on DOPC model membranes, but nisin
      showed reduced carboxyfluorescein leakage in DPoPC membranes containing
      cholesterol. In conclusion, bovicin HC5 only exerted cytotoxic effects at
      concentrations that were greater than the concentration needed for its biological
      activity, and the presence of cholesterol did not affect its interaction with
      model membranes.

PMID- 22956758
TI  - A sigmaD-dependent antisense transcript modulates expression of the cyclic-di-AMP
      hydrolase GdpP in Bacillus subtilis.
AB  - Cyclic-di-AMP (c-di-AMP) is an essential second messenger in Bacillus subtilis,
      and depletion leads to defects in the integrity of the cell wall. Levels of c-di
      AMP are regulated by both the rates of synthesis (by diadenylate cyclases) and
      the rates of degradation (by the GdpP phosphodiesterase, formerly YybT). Little
      is known about the regulation of gdpP expression or GdpP activity, but mutations
      that inactivate GdpP lead to high-level resistance to beta-lactam antibiotics.
      Here we demonstrate that expression of gdpP is regulated by a cis-acting
      antisense RNA (gdpP(as)) in vivo. Transcription of this antisense RNA is
      initiated in the middle of the gdp gene and is dependent on an alternative sigma
      factor, sigma(D), previously associated with the expression of late flagellar
      genes, chemotaxis proteins and cell wall autolytic enzymes. Changes in sigma(D)
      activity can modulate GdpP protein levels by ~2.5-fold, which may provide a
      mechanism for the cell to upregulate c-di-AMP levels in coordination with the
      activation of autolytic enzymes.

PMID- 22956759
TI  - Identification of triclosan-degrading bacteria using stable isotope probing,
      fluorescence in situ hybridization and microautoradiography.
AB  - Triclosan is considered a ubiquitous pollutant and can be detected in a wide
      range of environmental samples. Triclosan removal by wastewater treatment plants
      has been largely attributed to biodegradation processes; however, very little is
      known about the micro-organisms involved. In this study, DNA-based stable isotope
      probing (DNA-SIP) combined with microautoradiography-fluorescence in situ
      hybridization (MAR-FISH) was applied to identify active triclosan degraders in an
      enrichment culture inoculated with activated sludge. Clone library sequences of
      16S rRNA genes derived from the heavy DNA fractions of enrichment culture
      incubated with (13)C-labelled triclosan showed a predominant enrichment of a
      single bacterial clade most closely related to the betaproteobacterial genus
      Methylobacillus. To verify that members of the genus Methylobacillus were
      actively utilizing triclosan, a specific probe targeting the Methylobacillus
      group was designed and applied to the enrichment culture incubated with (14)C
      labelled triclosan for MAR-FISH. The MAR-FISH results confirmed a positive uptake
      of carbon from (14)C-labelled triclosan by the Methylobacillus. The high
      representation of Methylobacillus in the (13)C-labelled DNA clone library and its
      observed utilization of (14)C-labelled triclosan by MAR-FISH reveal that these
      micro-organisms are the primary consumers of triclosan in the enrichment culture.
      The results from this study show that the combination of SIP and MAR-FISH can
      shed light on the networks of uncultured micro-organisms involved in degradation
      of organic micro-pollutants.

PMID- 22956760
TI  - Neutrophil extracellular traps: double-edged swords of innate immunity.
AB  - Spectacular images of neutrophils ejecting nuclear chromatin and bactericidal
      proteins, in response to microbes, were first reported in 2004. As externalized
      chromatin could entangle bacteria, these structures were named neutrophil
      extracellular traps (NETs). Subsequent studies identified microorganisms and
      sterile conditions that stimulate NETs, as well as additional cell types that
      release extracellular chromatin. The release of NETs is the most dramatic stage
      in a cell death process called NETosis. Experimental evidence suggests that NETs
      participate in pathogenesis of autoimmune and inflammatory disorders, with
      proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and
      vascular disorders. Exaggerated NETosis or diminished NET clearance likely
      increases risk of autoreactivity to NET components. The biological significance
      of NETs is just beginning to be explored. A more complete integration of NETosis
      within immunology and pathophysiology will require better understanding of NET
      properties associated with specific disease states and microbial infections. This
      may lead to the identification of important therapeutic targets.

PMID- 22956761
TI  - Retraction: Recombinant migration inhibitory factor induces nitric oxide synthase
      in murine macrophages.

PMID- 22956762
TI  - Retraction: Human recombinant migration inhibitory factor activates human
      macrophages to kill Leishmania donovani.

PMID- 22956763
TI  - Retraction: Sphingosine kinase1 is pivotal for Fc"RI-mediated mast cell signaling
      and functional responses in vitro and in vivo.

PMID- 22956764
TI  - A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate
      accumulation mechanism for N-linked glycosylation deficiency.
AB  - Congenital disorder of glycosylation (PMM2-CDG) results from mutations in pmm2,
      which encodes the phosphomannomutase (Pmm) that converts mannose-6-phosphate
      (M6P) to mannose-1-phosphate (M1P). Patients have wide-spectrum clinical
      abnormalities associated with impaired protein N-glycosylation. Although it has
      been widely proposed that Pmm2 deficiency depletes M1P, a precursor of GDP
      mannose, and consequently suppresses lipid-linked oligosaccharide (LLO) levels
      needed for N-glycosylation, these deficiencies have not been demonstrated in
      patients or any animal model. Here we report a morpholino-based PMM2-CDG model in
      zebrafish. Morphant embryos had developmental abnormalities consistent with PMM2
      CDG patients, including craniofacial defects and impaired motility associated
      with altered motor neurogenesis within the spinal cord. Significantly, global N
      linked glycosylation and LLO levels were reduced in pmm2 morphants. Although M1P
      and GDP-mannose were below reliable detection/quantification limits, Pmm2
      depletion unexpectedly caused accumulation of M6P, shown earlier to promote LLO
      cleavage in vitro. In pmm2 morphants, the free glycan by-products of LLO cleavage
      increased nearly twofold. Suppression of the M6P-synthesizing enzyme mannose
      phosphate isomerase within the pmm2 background normalized M6P levels and certain
      aspects of the craniofacial phenotype and abrogated pmm2-dependent LLO cleavage.
      In summary, we report the first zebrafish model of PMM2-CDG and uncover novel
      cellular insights not possible with other systems, including an M6P accumulation
      mechanism for underglycosylation.

PMID- 22956765
TI  - The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens
      junctions through control of beta-catenin phosphorylation.
AB  - Impaired endothelial barrier function results in a persistent increase in
      endothelial permeability and vascular leakage. Repair of a dysfunctional
      endothelial barrier requires controlled restoration of adherens junctions,
      comprising vascular endothelial (VE)-cadherin and associated beta-, gamma-, alpha
      , and p120-catenins. Little is known about the mechanisms by which recovery of VE
      cadherin-mediated cell-cell junctions is regulated. Using the inflammatory
      mediator thrombin, we demonstrate an important role for the Src homology 2-domain
      containing tyrosine phosphatase (SHP2) in mediating recovery of the VE-cadherin
      controlled endothelial barrier. Using SHP2 substrate-trapping mutants and an in
      vitro phosphatase activity assay, we validate beta-catenin as a bona fide SHP2
      substrate. SHP2 silencing and SHP2 inhibition both result in delayed recovery of
      endothelial barrier function after thrombin stimulation. Moreover, on thrombin
      challenge, we find prolonged elevation in tyrosine phosphorylation levels of VE
      cadherin-associated beta-catenin in SHP2-depleted cells. No disassembly of the VE
      cadherin complex is observed throughout the thrombin response. Using fluorescence
      recovery after photobleaching, we show that loss of SHP2 reduces the mobility of
      VE-cadherin at recovered cell-cell junctions. In conclusion, our data show that
      the SHP2 phosphatase plays an important role in the recovery of disrupted
      endothelial cell-cell junctions by dephosphorylating VE-cadherin-associated beta
      catenin and promoting the mobility of VE-cadherin at the plasma membrane.

PMID- 22956766
TI  - Mammalian SEPT9 isoforms direct microtubule-dependent arrangements of septin core
      heteromers.
AB  - Septin-family proteins assemble into rod-shaped heteromeric complexes that form
      higher-order arrangements at the cell cortex, where they serve apparently
      conserved functions as diffusion barriers and molecular scaffolds. There are 13
      confirmed septin paralogues in mammals, which may be ubiquitous or tissue
      specific. Septin hetero-oligomerization appears homology subgroup directed, which
      in turn determines the subunit arrangement of six- to eight-subunit core
      heteromers. Here we address functional properties of human SEPT9, which, due to
      variable mRNA splicing, exists as multiple isoforms that differ between tissues.
      Myeloid K562 cells express three SEPT9 isoforms, all of which have an equal
      propensity to hetero-oligomerize with SEPT7-containing hexamers to generate
      octameric heteromers. However, due to limiting amounts of SEPT9, K562 cells
      contain both hexameric and octameric heteromers. To generate cell lines with
      controllable hexamer-to-octamer ratios and that express single SEPT9 isoforms, we
      developed a gene product replacement strategy. By this means we identified SEPT9
      isoform-specific properties that either facilitate septin heteromer
      polymerization along microtubules or modulate the size range of submembranous
      septin disks-a prevalent septin structure in nonadhered cells. Our findings show
      that the SEPT9 expression level directs the hexamer-to-octamer ratio, and that
      the isoform composition and expression level together determine higher-order
      arrangements of septins.

PMID- 22956767
TI  - The methyltransferase adaptor protein Trm112 is involved in biogenesis of both
      ribosomal subunits.
AB  - We previously identified Bud23 as the methyltransferase that methylates G1575 of
      rRNA in the P-site of the small (40S) ribosomal subunit. In this paper, we show
      that Bud23 requires the methyltransferase adaptor protein Trm112 for stability in
      vivo. Deletion of Trm112 results in a bud23Delta-like mutant phenotype. Thus
      Trm112 is required for efficient small-subunit biogenesis. Genetic analysis
      suggests the slow growth of a trm112Delta mutant is due primarily to the loss of
      Bud23. Surprisingly, suppression of the bud23Delta-dependent 40S defect revealed
      a large (60S) biogenesis defect in a trm112Delta mutant. Using sucrose gradient
      sedimentation analysis and coimmunoprecipitation, we show that Trm112 is also
      involved in 60S subunit biogenesis. The 60S defect may be dependent on Nop2 and
      Rcm1, two additional Trm112 interactors that we identify. Our work extends the
      known range of Trm112 function from modification of tRNAs and translation factors
      to both ribosomal subunits, showing that its effects span all aspects of the
      translation machinery. Although Trm112 is required for Bud23 stability, our
      results suggest that Trm112 is not maintained in a stable complex with Bud23. We
      suggest that Trm112 stabilizes its free methyltransferase partners not engaged
      with substrate and/or helps to deliver its methyltransferase partners to their
      substrates.

PMID- 22956768
TI  - The Hog1 SAPK controls the Rtg1/Rtg3 transcriptional complex activity by multiple
      regulatory mechanisms.
AB  - Cells modulate expression of nuclear genes in response to alterations in
      mitochondrial function, a response termed retrograde (RTG) regulation. In budding
      yeast, the RTG pathway relies on Rtg1 and Rtg3 basic helix-loop-helix leucine
      Zipper transcription factors. Exposure of yeast to external hyperosmolarity
      activates the Hog1 stress-activated protein kinase (SAPK), which is a key player
      in the regulation of gene expression upon stress. Several transcription factors,
      including Sko1, Hot1, the redundant Msn2 and Msn4, and Smp1, have been shown to
      be directly controlled by the Hog1 SAPK. The mechanisms by which Hog1 regulates
      their activity differ from one to another. In this paper, we show that Rtg1 and
      Rtg3 transcription factors are new targets of the Hog1 SAPK. In response to
      osmostress, RTG-dependent genes are induced in a Hog1-dependent manner, and Hog1
      is required for Rtg1/3 complex nuclear accumulation. In addition, Hog1 activity
      regulates Rtg1/3 binding to chromatin and transcriptional activity. Therefore
      Hog1 modulates Rtg1/3 complex activity by multiple mechanisms in response to
      stress. Overall our data suggest that Hog1, through activation of the RTG
      pathway, contributes to ensure mitochondrial function as part of the Hog1
      mediated osmoadaptive response.

PMID- 22956770
TI  - Human antral follicles <6 mm: a comparison between in vivo maturation and in
      vitro maturation in non-hCG primed cycles using cumulus cell gene expression.
AB  - Within the context of an oocyte in vitro maturation (IVM) program for
      reproductive treatment, oocyte cumulus complexes (COCs) derived from follicles <6
      mm in patients with PCOS were matured in vitro. Key transcripts related to
      meiotic maturation (FSHR, LHCGR, EGFR, PGR) and oocyte competence (AREG, ADAMTS,
      HAS2, PTGS2) were quantified in cumulus cells (CCs) before and after maturation.
      Control CC samples were collected from PCOS and normo-ovulatory patients who had
      undergone conventional gonadotrophin stimulation for IVF/ICSI. Additional control
      samples from a non-stimulated condition were obtained ex vivo from patients
      undergoing ovariectomy for fertility preservation. Expression data from CCs from
      follicles with a diameter of <6 mm before (IVM-CCs) and after in vitro maturation
      (IVM-CCs) were obtained after pooling CCs into four groups in relation to the
      percentage of matured (MII) oocytes obtained after 40 h of IVM (0; 40-60; 61-80;
      100% MII) and values were compared with in vivo matured controls (IVO-CCs). Genes
      encoding key receptors mediating meiotic resumption are expressed in human antral
      follicles of <6 mm before and after IVM. The expression levels of FSHR, EGFR and
      PGR in CCs were significantly down-regulated in the IVO-CCs groups and in the
      100% MII IVM group compared with the BM groups; all the receptors studied in the
      100% MII IVM group reached an expression profile similar to that of IVO-CCs.
      However, after maturation in a conventional IVF/ICSI cycle, IVO-CCs from large
      follicles contained significantly increased levels of ADAMTS1, AREG, HAS2 and
      PTGS2 compared with IVM-CCs and IVM-CCs; the expression patterns for these genes
      in all IVM-CCs were unchanged compared with IVM-CCs. In conclusion, genes
      encoding receptors involved in oocyte meiotic resumption appeared to be expressed
      in CCs of small human antral follicles. Expression levels of genes-encoding
      factors reflecting oocyte competence were significantly altered in IVM-CCs
      compared with in vivo matured oocytes from large follicles. Observed differences
      might be explained by the different stimulation protocols, doses of gonadotrophin
      or by the intrinsic differences between in vivo and in vitro maturation.

PMID- 22956769
TI  - BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular
      structures.
AB  - Cytoplasmic dynein is the major microtubule minus-end-directed cellular motor.
      Most dynein activities require dynactin, but the mechanisms regulating cargo
      dependent dynein-dynactin interaction are poorly understood. In this study, we
      focus on dynein-dynactin recruitment to cargo by the conserved motor adaptor
      Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for
      BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly
      promotes stable interaction between dynein and dynactin both in vitro and in
      vivo. Direct visualization of dynein in live cells indicates that by itself the
      triple BICD2-N-dynein-dynactin complex is unable to interact with either cargo or
      microtubules. However, tethering of BICD2-N to different membranes promotes their
      microtubule minus-end-directed motility. We further show that LIS1 is required
      for dynein-mediated transport induced by membrane tethering of BICD2-N and that
      LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2
      positive cellular structures. Our results demonstrate that dynein recruitment to
      cargo requires concerted action of multiple dynein cofactors.

PMID- 22956771
TI  - Extracellular quaternary ammonium blockade of transient receptor potential
      vanilloid subtype 1 channels expressed in Xenopus laevis oocytes.
AB  - Transient receptor potential vanilloid subtype 1 (TRPV1) channels are essential
      nociceptive integrators in primary afferent neurons. These nonselective cation
      channels are inhibited by local anesthetic compounds through an undefined
      mechanism. Here, we show that lidocaine inhibits TRPV1 channels expressed in
      Xenopus laevis oocytes, whereas the neutral local anesthetic, benzocaine, does
      not, suggesting that a titratable amine is required for high-affinity inhibition.
      Consistent with this possibility, extracellular tetraethylammonium (TEA) and
      tetramethylammonium application produces potent, voltage-dependent pore block.
      Alanine substitutions at Phe649 and Glu648, residues in the putative TRPV1 pore
      region, significantly abrogated the concentration-dependent TEA inhibition. The
      results suggest that large cations, shown previously to enter cells through
      activated transient receptor potential channels, can also act as channel
      blockers.

PMID- 22956772
TI  - Betulinic acid decreases specificity protein 1 (Sp1) level via increasing the
      sumoylation of sp1 to inhibit lung cancer growth.
AB  - Previous studies have shown that the inhibitory effect of betulinic acid (BA) on
      specificity protein 1 (Sp1) expression is involved in the prevention of cancer
      progression, but the mechanism of this effect remains to be delineated. In this
      study, we determined that BA treatment in HeLa cells increased the sumoylation of
      Sp1 by inhibiting sentrin-specific protease 1 expression. The subsequent
      recruitment of E3 ubiquitin-protein ligase RING finger protein 4 resulted in
      ubiquitin-mediated degradation in a 26S-proteosome-dependent pathway. In
      addition, both BA treatment and mithramycin A (MMA) treatment inhibited lung
      tumor growth and down-regulated Sp1 protein expression in Kras(G12D)-induced lung
      cancers of bitransgenic mice. In gene expression profiles of Kras(G12D)-induced
      lung cancers in bitransgenic mice with and without Sp1 inhibition, 542 genes were
      affected by MMA treatment. One of the gene products, cyclin A2, which was
      involved in the S and G(2)/M phase transition during cell cycle progression, was
      investigated in detail because its expression was regulated by Sp1. The down
      regulation of cyclin A2 by BA treatment resulted in decreased retinoblastoma
      protein phosphorylation and cell cycle G(2)/M arrest. The BA-mediated cellular
      Sp1 degradation and antitumor effect were also confirmed in a xenograft mouse
      model by using H1299 cells. The knockdown of Sp1 in lung cancer cells attenuated
      the tumor-suppressive effect of BA. Taken together, the results of this study
      clarify the mechanism of BA-mediated Sp1 degradation and identify a pivotal role
      for Sp1 in the BA-induced repression of lung cancer growth.

PMID- 22956781
TI  - Proinflammatory effects of malondialdehyde in lymphocytes.
AB  - Diabetes is an inflammatory disease promoted by alterations in immune cell
      function. Animal study indicates that T cells are important mediators of
      inflammation in diabetes. Lipid peroxidation by reactive oxygen species leads to
      the formation of highly reactive malondialdehyde (MDA), and extensive MDA is
      found in diabetes. However, the biological functions of MDA have not been studied
      yet. We hypothesized that increased MDA, as in diabetes, can regulate
      inflammatory cytokines via specific signaling pathways. This could then result in
      increased lymphocyte activation and skewing a particular inflammatory subset
      thereby exacerbates diabetes complications. Commercial cytokine antibody and
      RT(2)-PCR array profiling were performed with Jurkat T cells grown with or
      without MDA. Ingenuity pathways analysis (IPA) and pharmacological inhibitors
      were used for networks and signaling pathway identification, respectively. For
      validation, real-time PCR, RT-PCR, and Western blots were performed. MDA induced
      significant increases in 47 key proinflammatory molecules such as IL-25, IL-6, IL
      8, ICAM-1, and light mRNA in Jurkat T cells and primary peripheral blood
      lymphocytes (PBLCs). A significant 2-fold increase in serum MDA also correlated
      the increased IL-25 and IL-8 mRNA in PBLCs of diabetic patients. Pharmacological
      inhibitor studies showed that MDA induced its effect via p38MAPK and protein
      kinase C pathways. Furthermore, IPA uncovered 5 groups of inflammatory networks
      and placed our candidate genes in canonical IL-6 and NF-kappaB signaling pathways
      and also suggested 5 toxic lists and 3 major toxic functions, namely
      cardiotoxicity, hepatotoxicity, and nephrotoxicity. These new results suggest
      that MDA can promote lymphocyte activation via induction of inflammatory pathways
      and networks.

PMID- 22956783
TI  - microRNA-181a represses ox-LDL-stimulated inflammatory response in dendritic cell
      by targeting c-Fos.
AB  - Oxidized LDL (ox-LDL) activates dendritic cells (DCs), thereby initiating
      inflammation responses in atherosclerosis, yet the modulatory mechanisms remain
      unclear. MicroRNAs (miRNAs) are important regulators for DC functions. This study
      evaluated the regulation by miRNAs of the ox-LDL-induced DC immune response. In
      CD11c(+) DCs from ApoE-deficient mice with hyperlipidemia, microRNA miR-181a was
      significantly up-regulated. In cultured bone marrow-derived DCs (BMDCs), ox-LDL
      promoted DC maturation and up-regulated miR-181a expression. Abundance of miR
      181a attenuated ox-LDL-induced CD83 and CD40 expression, inhibited the secretion
      of interleukin (IL)-6 and TNF-alpha, and up-regulated IL-10, an important anti
      inflammatory cytokine that was inhibited by ox-LDL. Inhibition of the endogenous
      miR-181a reversed the effects on CD83 and CD40 as well as the effects on IL-6 and
      TNF-alpha. The putative target genes of miR-181a were evaluated by gene ontology
      assessment, and the c-Fos-mediated inflammation pathway was identified. miR-181a
      targeted the 3' untranslated region of c-Fos mRNA by luciferase experiments.
      Thus, abundance of miR-181a reduced c-Fos protein, whereas inhibition of miR-181a
      increased c-Fos protein in BMDCs. We therefore suggest that miR-181a attenuates
      ox-LDL-stimulated immune inflammation responses by targeting c-Fos in DCs.

PMID- 22956784
TI  - Inhibition of intestinal cholesterol absorption decreases atherosclerosis but not
      adipose tissue inflammation.
AB  - Adipose tissue inflammation is associated with insulin resistance and increased
      cardiovascular disease risk in obesity. We previously showed that addition of
      cholesterol to a diet rich in saturated fat and refined carbohydrate
      significantly worsens dyslipidemia, insulin resistance, adipose tissue macrophage
      accumulation, systemic inflammation, and atherosclerosis in LDL receptor
      deficient (Ldlr(-/-)) mice. To test whether inhibition of intestinal cholesterol
      absorption would improve metabolic abnormalities and adipose tissue inflammation
      in obesity, we administered ezetimibe, a dietary and endogenous cholesterol
      absorption inhibitor, to Ldlr(-/-) mice fed chow or high-fat, high-sucrose (HFHS)
      diets without or with 0.15% cholesterol (HFHS+C). Ezetimibe blunted weight gain
      and markedly reduced plasma lipids in the HFHS+C group. Ezetimibe had no effect
      on glucose homeostasis or visceral adipose tissue macrophage gene expression in
      the HFHS+C fed mice, although circulating inflammatory markers serum amyloid A
      (SSA) and serum amyloid P (SSP) levels decreased. Nevertheless, ezetimibe
      treatment led to a striking (>85%) reduction in atherosclerotic lesion area with
      reduced lesion lipid and macrophage content in the HFHS+C group. Thus, in the
      presence of dietary cholesterol, ezetimibe did not improve adipose tissue
      inflammation in obese Ldlr(-/-) mice, but it led to a major reduction in
      atherosclerotic lesions associated with improved plasma lipids and lipoproteins.

PMID- 22956786
TI  - The gating of neocortical information by modulators.
AB  - Thalamic input to the neocortex is crucial for sensory perception and constitutes
      the basis of complex awake behavior. Connections within the neocortex play an
      important role in internally generated neural activity, which is considered
      critical for memory retrieval and for the generation of imagery in our dreams.
      Modulatory neurotransmitters, such as noradrenaline and acetylcholine, gate
      information transmission in the brain. Favero et al. (J Neurophysiol 108: 1010
      1024, 2012) show that modulators differentially facilitate thalamocortical
      relative to intracortical transmission in the input layers of cortex.

PMID- 22956785
TI  - Response variability of frontal eye field neurons modulates with sensory input
      and saccade preparation but not visual search salience.
AB  - Discharge rate modulation of frontal eye field (FEF) neurons has been identified
      with a representation of visual search salience (physical conspicuity and
      behavioral relevance) and saccade preparation. We tested whether salience or
      saccade preparation are evident in the trial-to-trial variability of discharge
      rate. We quantified response variability via the Fano factor in FEF neurons
      recorded in monkeys performing efficient and inefficient visual search tasks.
      Response variability declined following stimulus presentation in most neurons,
      but despite clear discharge rate modulation, variability did not change with
      target salience. Instead, we found that response variability was modulated by
      stimulus luminance and the number of items in the visual field independently of
      attentional demands. Response variability declined to a minimum before saccade
      initiation, and presaccadic response variability was directionally tuned. In
      addition, response variability was correlated with the response time of memory
      guided saccades. These results indicate that the trial-by-trial response
      variability of FEF neurons reflects saccade preparation and the strength of
      sensory input, but not visual search salience or attentional allocation.

PMID- 22956789
TI  - Somatic and dendritic GABA(B) receptors regulate neuronal excitability via
      different mechanisms.
AB  - GABA(B) receptors play a key role in regulating neuronal excitability in the
      brain. Whereas the impact of somatic GABA(B) receptors on neuronal excitability
      has been studied in some detail, much less is known about the role of dendritic
      GABA(B) receptors. Here, we investigate the impact of GABA(B) receptor activation
      on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat
      barrel cortex. Activation of GABA(B) receptors led to hyperpolarization and a
      decrease in membrane resistance that was greatest at somatic and proximal
      dendritic locations. These effects were occluded by low concentrations of barium
      (100 MUM), suggesting that they are mediated by potassium channels. In contrast,
      activation of dendritic GABA(B) receptors decreased the width of backpropagating
      action potential (APs) and abolished dendritic calcium electrogenesis, indicating
      that dendritic GABA(B) receptors regulate excitability, primarily via inhibition
      of voltage-dependent calcium channels. These distinct actions of somatic and
      dendritic GABA(B) receptors regulated neuronal output in different ways.
      Activation of somatic GABA(B) receptors led to a reduction in neuronal output,
      primarily by increasing the AP rheobase, whereas activation of dendritic GABA(B)
      receptors blocked burst firing, decreasing AP output in the absence of a
      significant change in somatic membrane properties. Taken together, our results
      show that GABA(B) receptors regulate somatic and dendritic excitability of
      cortical pyramidal neurons via different cellular mechanisms. Somatic GABA(B)
      receptors activate potassium channels, leading primarily to a subtractive or
      shunting form of inhibition, whereas dendritic GABA(B) receptors inhibit
      dendritic calcium electrogenesis, leading to a reduction in bursting firing.

PMID- 22956790
TI  - Relationships between neck muscle electromyography and three-dimensional head
      kinematics during centrally induced torsional head perturbations.
AB  - The relationship between neck muscle electromyography (EMG) and torsional head
      rotation (about the nasooccipital axis) is difficult to assess during normal gaze
      behaviors with the head upright. Here, we induced acute head tilts similar to
      cervical dystonia (torticollis) in two monkeys by electrically stimulating 20
      interstitial nucleus of Cajal (INC) sites or inactivating 19 INC sites by
      injection of muscimol. Animals engaged in a simple gaze fixation task while we
      recorded three-dimensional head kinematics and intramuscular EMG from six
      bilateral neck muscle pairs. We used a cross-validation-based stepwise regression
      to quantitatively examine the relationships between neck EMG and torsional head
      kinematics under three conditions: 1) unilateral INC stimulation (where the head
      rotated torsionally toward the side of stimulation); 2) corrective
      poststimulation movements (where the head returned toward upright); and 3)
      unilateral INC inactivation (where the head tilted toward the opposite side of
      inactivation). Our cross-validated results of corrective movements were slightly
      better than those obtained during unperturbed gaze movements and showed many more
      torsional terms, mostly related to velocity, although some orientation and
      acceleration terms were retained. In addition, several simplifying principles
      were identified. First, bilateral muscle pairs showed similar, but opposite EMG
      torsional coupling terms, i.e., a change in torsional kinematics was associated
      with increased muscle activity on one side and decreased activity on the other
      side. s, whenever torsional terms were retained in a given muscle, they were
      independent of the inputs we tested, i.e., INC stimulation vs. corrective motion
      vs. INC inactivation, and left vs. right INC data. These findings suggest that,
      despite the complexity of the head-neck system, the brain can use a single,
      bilaterally coupled inverse model for torsional head control that is valid across
      different behaviors and movement directions. Combined with our previous data,
      these new data provide the terms for a more complete three-dimensional model of
      EMG: head rotation coupling for the muscles and gaze behaviors that we recorded.

PMID- 22956787
TI  - Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to salty
      and sour taste stimuli.
AB  - The relationship between taste receptor cell (TRC) Ca(2+) concentration
      ([Ca(2+)](i)) and rat chorda tympani (CT) nerve responses to salty [NaCl and
      NaCl+benzamil (Bz)] and sour (HCl, CO(2), and acetic acid) taste stimuli was
      investigated before and after lingual application of ionomycin+Ca(2+), 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM),
      U73122 (phospholipase C blocker), and thapsigargin (Ca(2+)-ATPase inhibitor)
      under open-circuit or lingual voltage-clamp conditions. An increase in TRC
      [Ca(2+)](i) attenuated the tonic Bz-sensitive NaCl CT response and the apical
      membrane Na(+) conductance. A decrease in TRC [Ca(2+)](i) enhanced the tonic Bz
      sensitive and Bz-insensitive NaCl CT responses and apical membrane Na(+)
      conductance but did not affect CT responses to KCl or NH(4)Cl. An increase in TRC
      [Ca(2+)](i) did not alter the phasic response but attenuated the tonic CT
      response to acidic stimuli. A decrease in [Ca(2+)](i) did not alter the phasic
      response but attenuated the tonic CT response to acidic stimuli. In a subset of
      TRCs, a positive relationship between [H(+)](i) and [Ca(2+)](i) was obtained
      using in vitro imaging techniques. U73122 inhibited the tonic CT responses to
      NaCl, and thapsigargin inhibited the tonic CT responses to salty and sour
      stimuli. The results suggest that salty and sour taste qualities are transduced
      by [Ca(2+)](i)-dependent and [Ca(2+)](i)-independent mechanisms. Changes in TRC
      [Ca(2+)](i) in a BAPTA-sensitive cytosolic compartment regulate ion channels and
      cotransporters involved in the salty and sour taste transduction mechanisms and
      in neural adaptation. Changes in TRC [Ca(2+)](i) in a separate subcompartment,
      sensitive to inositol trisphosphate and thapsigargin but inaccessible to BAPTA,
      are associated with neurotransmitter release.

PMID- 22956788
TI  - Knockouts reveal overlapping functions of M(2) and M(4) muscarinic receptors and
      evidence for a local glutamatergic circuit within the laterodorsal tegmental
      nucleus.
AB  - Cholinergic neurons in the laterodorsal tegmental (LDT) and peduncolopontine
      tegmental (PPT) nuclei regulate reward, arousal, and sensory gating via major
      projections to midbrain dopamine regions, the thalamus, and pontine targets.
      Muscarinic acetylcholine receptors (mAChRs) on LDT neurons produce a membrane
      hyperpolarization and inhibit spike-evoked Ca(2+) transients. Pharmacological
      studies suggest M(2) mAChRs are involved, but the role of these and other
      localized mAChRs (M(1-)-M(4)) has not been definitively tested. To identify the
      underlying receptors and to circumvent the limited receptor selectivity of
      available mAChR ligands, we used light- and electron-immunomicroscopy and whole
      cell recording with Ca(2+) imaging in brain slices from knockout mice
      constitutively lacking either M(2), M(4), or both mAChRs. Immunomicroscopy
      findings support a role for M(2) mAChRs, since cholinergic and noncholinergic LDT
      and pedunculopontine tegmental neurons contain M(2)-specific immunoreactivity.
      However, whole cell recording revealed that the presence of either M(2) or M(4)
      mAChRs was sufficient, and that the presence of at least one of these receptors
      was required for these carbachol actions. Moreover, in the absence of M(2) and
      M(4) mAChRs, carbachol elicited both direct excitation and barrages of
      spontaneous excitatory postsynaptic potentials (sEPSPs) in cholinergic LDT
      neurons mediated by M(1) and/or M(3) mAChRs. Focal carbachol application to
      surgically reduced slices suggest that local glutamatergic neurons are a source
      of these sEPSPs. Finally, neither direct nor indirect excitation were knockout
      artifacts, since each was detected in wild-type slices, although sEPSP barrages
      were delayed, suggesting M(2) and M(4) receptors normally delay excitation of
      glutamatergic inputs. Collectively, our findings indicate that multiple mAChRs
      coordinate cholinergic outflow from the LDT in an unexpectedly complex manner. An
      intriguing possibility is that a local circuit transforms LDT muscarinic inputs
      from a negative feedback signal for transient inputs into positive feedback for
      persistent inputs to facilitate different firing patterns across behavioral
      states.

PMID- 22956791
TI  - Role of Ih in the firing pattern of mammalian cold thermoreceptor endings.
AB  - Mammalian peripheral cold thermoreceptors respond to cooling of their sensory
      endings with an increase in firing rate and modification of their discharge
      pattern. We recently showed that cultured trigeminal cold-sensitive (CS) neurons
      express a prominent hyperpolarization-activated current (I(h)), mainly carried by
      HCN1 channels, supporting subthreshold resonance in the soma without
      participating in the response to acute cooling. However, peripheral
      pharmacological blockade of I(h), or characterization of HCN1(-/-) mice, reveals
      a deficit in acute cold detection. Here we investigated the role of I(h) in CS
      nerve endings, where cold sensory transduction actually takes place. Corneal CS
      nerve endings in mice show a rhythmic spiking activity at neutral skin
      temperature that switches to bursting mode when the temperature is lowered. I(h)
      blockers ZD7288 and ivabradine alter firing patterns of CS nerve endings,
      lengthening interspike intervals and inducing bursts at neutral skin temperature.
      We characterized the CS nerve endings from HCN1(-/-) mouse corneas and found that
      they behave similar to wild type, although with a lower slope in the firing
      frequency vs. temperature relationship, thus explaining the deficit in cold
      perception of HCN1(-/-) mice. The firing pattern of nerve endings from HCN1(-/-)
      mice was also affected by ZD7288, which we attribute to the presence of HCN2
      channels in the place of HCN1. Mathematical modeling shows that the firing
      phenotype of CS nerve endings from HCN1(-/-) mice can be reproduced by replacing
      HCN1 channels with the slower HCN2 channels rather than by abolishing I(h). We
      propose that I(h) carried by HCN1 channels helps tune the frequency of the
      oscillation and the length of bursts underlying regular spiking in cold
      thermoreceptors, having important implications for neural coding of cold
      sensation.

PMID- 22956782
TI  - Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle:
      the Look AHEAD Study.
AB  - Adipose tissue dysfunction plays a key role in the development of the metabolic
      abnormalities characteristic of type 2 diabetes (T2DM) and participates actively
      in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of
      adipose health, is decreased in obese persons with T2DM. We investigated whether
      the changes in adiponectin with an intensive lifestyle intervention (ILI) for
      weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C)
      with ILI. Adiponectin and its fractions were determined using an ELISA with
      selective protease treatment in 1,397 participants from Look AHEAD, a trial
      examining whether ILI will reduce cardiovascular events in overweight/obese
      subjects with T2DM when compared with a control arm, diabetes support and
      education (DSE). Multivariable regression and mediational analyses were performed
      for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI
      increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were
      1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight,
      fitness, triglycerides, and glucose control and that adjusted for demographics
      and medical history, adiponectin changes remained significantly associated with
      HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW
      adiponectin to the improvement in HDL-C with ILI.

PMID- 22956792
TI  - Dramatic impairment of prediction due to frontal lobe degeneration.
AB  - Prediction is essential for motor function in everyday life. For instance,
      predictive mechanisms improve the perception of a moving target by increasing eye
      speed anticipatively, thus reducing motion blur on the retina. Subregions of the
      frontal lobes play a key role in eye movements in general and in smooth pursuit
      in particular, but their precise function is not firmly established. Here, the
      role of frontal lobes in the timing of predictive action is demonstrated by
      studying predictive smooth pursuit during transient blanking of a moving target
      in mild frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD)
      patients. While control subjects and AD patients predictively reaccelerated their
      eyes before the predicted time of target reappearance, FTLD patients did not. The
      difference was so dramatic (classification accuracy >90%) that it could even lead
      to the definition of a new biomarker. In contrast, anticipatory eye movements
      triggered by the disappearance of the fixation point were still present before
      target motion onset in FTLD patients and visually guided pursuit was normal in
      both patient groups compared with controls. Therefore, FTLD patients were only
      impaired when the predicted timing of an external event was required to elicit an
      action. These results argue in favor of a role of the frontal lobes in predictive
      movement timing.

PMID- 22956794
TI  - The speed of morality: a high-density electrical neuroimaging study.
AB  - Neuroscience research indicates that moral reasoning is underpinned by distinct
      neural networks including the posterior superior temporal sulcus (pSTS),
      amygdala, and ventromedial prefrontal cortex, which support communication between
      computational systems underlying affective states, cognitions, and motivational
      processes. To characterize real-time neural processing underpinning moral
      computations, high-density event-related potentials were measured in participants
      while they viewed short, morally laden visual scenarios depicting intentional and
      accidental harmful actions. Current source density maxima in the right pSTS as
      fast as 62 ms poststimulus first distinguished intentional vs. accidental
      actions. Responses in the amygdala/temporal pole (122 ms) and ventromedial
      prefrontal cortex (182 ms) were then evoked by the perception of harmful actions,
      indicative of fast information processing associated with early stages of moral
      cognition. Our data strongly support the notion that intentionality is the first
      input to moral computations. They also demonstrate that emotion acts as a gain
      antecedent to moral judgment by alerting the individual to the moral salience of
      a situation and provide evidence for the pervasive role of affect in moral
      sensitivity and reasoning.

PMID- 22956793
TI  - Neck rotation modulates flexion synergy torques, indicating an ipsilateral
      reticulospinal source for impairment in stroke.
AB  - The effect of reticular formation excitability on maximum voluntary torque (MVT)
      generation and associated muscle activation at the shoulder and elbow was
      investigated through natural elicitation (active head rotation) of the asymmetric
      tonic neck reflex (ATNR) in 26 individuals with stroke and 9 age-range-matched
      controls. Isometric MVT generation at the shoulder and elbow was quantified with
      the head rotated (face pointing) contralateral and ipsilateral to the paretic
      (stroke) and dominant (control) arm. Given the dominance of abnormal torque
      coupling of elbow flexion with shoulder abduction (flexion synergy) in stroke and
      well-developed animal models demonstrating a linkage between reticular formation
      and ipsilateral elbow flexors and shoulder abductors, we hypothesized that
      constituent torques of flexion synergy, specifically elbow flexion and shoulder
      abduction, would increase with contralateral head rotation. The findings of this
      investigation support this hypothesis. Increases in MVT for three of four flexion
      synergy constituents (elbow flexion, shoulder abduction, and shoulder external
      rotation) were observed during contralateral head rotation only in individuals
      with stroke. Electromyographic data of the associated muscle coactivations were
      nonsignificant but are presented for consideration in light of a likely
      underpowered statistical design for this specific variable. This study not only
      provides evidence for the reemergence of ATNR following stroke but also indicates
      a common neuroanatomical link, namely, an increased reliance on ipsilateral
      reticulospinal pathways, as the likely mechanism underlying the expression of
      both ATNR and flexion synergy that results in the loss of independent joint
      control.

PMID- 22956796
TI  - Fentanyl decreases discharges of C and A nociceptors to suprathreshold mechanical
      stimulation in chronic inflammation.
AB  - An essential component of mechanical hyperalgesia resulting from tissue injury is
      an enhanced excitability of nociceptive neurons, termed mechanical sensitization.
      Local application of opioids to inflamed rat paws attenuates mechanical
      hyperalgesia and reduces electrical excitability of C-fiber nociceptors in acute
      injury. Here, we examined the effects of the opioid receptor agonist fentanyl on
      the mechanical coding properties of not only C- but also A-fiber nociceptors
      innervating the rat hind paw in a model of chronic pain, i.e., 4 days after
      Freund's complete adjuvant-induced inflammation. The peripheral mechanosensitive
      terminals of C-fibers (n = 143), A-fibers (n = 79), and low-threshold
      mechanoreceptors (n = 25) were characterized using the in vitro skin-nerve
      preparation from the saphenous nerve. Although mechanical activation thresholds
      were not changed, discharges to suprathreshold mechanical stimuli were elevated
      significantly in both A- and C-fiber nociceptors from inflamed tissue. In
      addition, the proportion of nociceptors as well as the frequency of spontaneous
      discharges in A (14% vs. 0%)- and C (28% vs. 8%)-fibers were increased in
      inflamed compared with normal tissue. Fentanyl inhibited responses to
      suprathreshold stimuli in a significantly higher proportion of not only C (36%
      vs. 7%)- but also A (41% vs. 8%)-fibers in inflamed tissue in a naloxone
      reversible and concentration-dependent manner. Our results demonstrate that
      mechanical sensitization persists in chronic inflammation, in correlation with
      behavioral hyperalgesia. Opioid sensitivity of both A- and C-fibers is markedly
      augmented. This is consistent with an upregulation or enhanced functionality of
      opioid receptors located at the peripheral terminals of sensitized nociceptors.

PMID- 22956795
TI  - Temporal stability of visually selective responses in intracranial field
      potentials recorded from human occipital and temporal lobes.
AB  - The cerebral cortex needs to maintain information for long time periods while at
      the same time being capable of learning and adapting to changes. The degree of
      stability of physiological signals in the human brain in response to external
      stimuli over temporal scales spanning hours to days remains unclear. Here, we
      quantitatively assessed the stability across sessions of visually selective
      intracranial field potentials (IFPs) elicited by brief flashes of visual stimuli
      presented to 27 subjects. The interval between sessions ranged from hours to
      multiple days. We considered electrodes that showed robust visual selectivity to
      different shapes; these electrodes were typically located in the inferior
      occipital gyrus, the inferior temporal cortex, and the fusiform gyrus. We found
      that IFP responses showed a strong degree of stability across sessions. This
      stability was evident in averaged responses as well as single-trial decoding
      analyses, at the image exemplar level as well as at the category level, across
      different parts of visual cortex, and for three different visual recognition
      tasks. These results establish a quantitative evaluation of the degree of
      stationarity of visually selective IFP responses within and across sessions and
      provide a baseline for studies of cortical plasticity and for the development of
      brain-machine interfaces.

PMID- 22956797
TI  - Effect of afferent feedback and central motor commands on soleus H-reflex
      suppression during arm cycling.
AB  - Suppression of soleus H-reflex amplitude in stationary legs is seen during
      rhythmic arm cycling. We examined the influence of various arm-cycling parameters
      on this interlimb reflex modulation to determine the origin of the effect. We
      previously showed the suppression to be graded with the frequency of arm cycling
      but not largely influenced by changes in peripheral input associated with crank
      length. Here, we more explicitly explored the contribution of afferent feedback
      related to arm movement on the soleus H-reflex suppression. We explored the
      influence of load and rate of muscle stretch by manipulating crank-load and arm
      muscle vibration during arm cycling. Furthermore, internally driven ("Active")
      and externally driven ("Passive") arm cycling was compared. Soleus H-reflexes
      were evoked with tibial nerve stimulation during stationary control and rhythmic
      arm-cycling conditions, including: 1) six different loads; 2) with and without
      vibration to arm muscles; and 3) Active and Passive conditions. No significant
      differences were seen in the level of suppression between the different crank
      loads or between conditions with and without arm-muscle vibration. Furthermore,
      in contrast to the clear effect seen during active cycling, passive arm cycling
      did not significantly suppress the soleus H-reflex amplitude. Current results, in
      conjunction with previous findings, suggest that the afferent feedback examined
      in these studies is not the primary source responsible for soleus H-reflex
      suppression. Instead, it appears that central motor commands (supraspinal or
      spinal in origin) associated with frequency of arm cycling are relatively more
      dominant sources.

PMID- 22956798
TI  - An involuntary stereotypical grasp tendency pervades voluntary dynamic
      multifinger manipulation.
AB  - We used a novel apparatus with three hinged finger pads to characterize
      collaborative multifinger interactions during dynamic manipulation requiring
      individuated control of fingertip motions and forces. Subjects placed the thumb,
      index, and middle fingertips on each hinged finger pad and held it-unsupported
      with constant total grasp force while voluntarily oscillating the thumb's pad.
      This task combines the need to 1) hold the object against gravity while 2)
      dynamically reconfiguring the grasp. Fingertip force variability in this combined
      motion and force task exhibited strong synchrony among normal (i.e., grasp)
      forces. Mechanical analysis and simulation show that such synchronous variability
      is unnecessary and cannot be explained solely by signal-dependent noise.
      Surprisingly, such variability also pervaded control tasks requiring different
      individuated fingertip motions and forces, but not tasks without finger
      individuation such as static grasp. These results critically extend notions of
      finger force variability by exposing and quantifying a pervasive challenge to
      dynamic multifinger manipulation: the need for the neural controller to carefully
      and continuously overlay individuated finger actions over mechanically
      unnecessary synchronous interactions. This is compatible with-and may explain-the
      phenomenology of strong coupling of hand muscles when this delicate balance is
      not yet developed, as in early childhood, or when disrupted, as in brain injury.
      We conclude that the control of healthy multifinger dynamic manipulation has
      barely enough neuromechanical degrees of freedom to meet the multiple demands of
      ecological tasks and critically depends on the continuous inhibition of
      synchronous grasp tendencies, which we speculate may be of vestigial evolutionary
      origin.

PMID- 22956799
TI  - Coapplication of noisy patterned electrical stimuli and NMDA plus serotonin
      facilitates fictive locomotion in the rat spinal cord.
AB  - A new stimulating protocol [fictive locomotion-induced stimulation (FListim)],
      consisting of intrinsically variable weak waveforms applied to a single dorsal
      root is very effective (though not optimal as it eventually wanes away) in
      activating the locomotor program of the isolated rat spinal cord. The present
      study explored whether combination of FListim with low doses of pharmacological
      agents that raise network excitability might further improve the functional
      outcome, using this in vitro model. FListim was applied together with N-methyl-d
      aspartate (NMDA) + serotonin, while fictive locomotion (FL) was
      electrophysiologically recorded from lumbar ventral roots. Superimposing FListim
      on FL evoked by these neurochemicals persistently accelerated locomotor-like
      cycles to a set periodicity and modulated cycle amplitude depending on FListim
      rate. Trains of stereotyped rectangular pulses failed to replicate this
      phenomenon. The GABA(B) agonist baclofen dose dependently inhibited, in a
      reversible fashion, FL evoked by either FListim or square pulses. Sustained
      episodes of FL emerged when FListim was delivered, at an intensity subthreshold
      for FL, in conjunction with subthreshold pharmacological stimulation. Such an
      effect was, however, not found when high potassium solution instead of NMDA +
      serotonin was used. These results suggest that the combined action of
      subthreshold FListim (e.g., via epidural stimulation) and neurochemicals should
      be tested in vivo to improve locomotor rehabilitation after injury. In fact,
      reactivation of spinal locomotor circuits by conventional electrical stimulation
      of afferent fibers is difficult, while pharmacological activation of spinal
      networks is clinically impracticable due to concurrent unwanted effects. We
      speculate that associating subthreshold chemical and electrical inputs might
      decrease side effects when attempting to evoke human locomotor patterns.

PMID- 22956802
TI  - Pathway-based oncology care: time for more transparency.

PMID- 22956800
TI  - Pain-facilitating medullary neurons contribute to opioid-induced respiratory
      depression.
AB  - Respiratory depression is a therapy-limiting side effect of opioid analgesics,
      yet our understanding of the brain circuits mediating this potentially lethal
      outcome remains incomplete. Here we studied the contribution of the rostral
      ventromedial medulla (RVM), a region long implicated in pain modulation and
      homeostatic regulation, to opioid-induced respiratory depression. Microinjection
      of the MU-opioid agonist DAMGO in the RVM of lightly anesthetized rats produced
      both analgesia and respiratory depression, showing that neurons in this region
      can modulate breathing. Blocking opioid action in the RVM by microinjecting the
      opioid antagonist naltrexone reversed the analgesic and respiratory effects of
      systemically administered morphine, showing that this region plays a role in both
      the analgesic and respiratory-depressant properties of systemically administered
      morphine. The distribution of neurons directly inhibited by RVM opioid
      microinjection was determined with a fluorescent opioid peptide, dermorphin-Alexa
      594, and found to be concentrated in and around the RVM. The non-opioid analgesic
      improgan, like DAMGO, produced antinociception but, unlike DAMGO, stimulated
      breathing when microinjected into the RVM. Concurrent recording of RVM neurons
      during improgan microinjection showed that this agent activated RVM ON-cells, OFF
      cells, and NEUTRAL-cells. Since opioids are known to activate OFF-cells but
      suppress ON-cell firing, the differential respiratory response to these two
      analgesic drugs is best explained by their opposing effects on the activity of
      RVM ON-cells. These findings show that pain relief can be separated
      pharmacologically from respiratory depression and identify RVM OFF-cells as
      important central targets for continued development of potent analgesics with
      fewer side effects.

PMID- 22956801
TI  - Presynaptic CaV2.1 calcium channels carrying familial hemiplegic migraine
      mutation R192Q allow faster recovery from synaptic depression in mouse calyx of
      Held.
AB  - Ca(V)2.1 Ca(2+) channels have a dominant and specific role in initiating fast
      synaptic transmission at central excitatory synapses, through a close association
      between release sites and calcium sensors. Familial hemiplegic migraine type 1
      (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by
      missense mutations in the CACNA1A gene that encodes the alpha(1A) pore-forming
      subunit of Ca(V)2.1 channel. We used knock-in (KI) transgenic mice harboring the
      FHM-1 mutation R192Q to study the consequences of this mutation in
      neurotransmission at the giant synapse of the auditory system formed by the
      presynaptic calyx of Held terminal and the postsynaptic neurons of the medial
      nucleus of the trapezoid body (MNTB). Although synaptic transmission seems
      unaffected by low-frequency stimulation in physiological Ca(2+) concentration, we
      observed that with low Ca(2+) concentrations (<1 mM) excitatory postsynaptic
      currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild
      type (WT), meaning significant differences in the nonlinear calcium dependence of
      nerve-evoked transmitter release. In addition, when EPSCs were evoked by
      broadened presynaptic action potentials (achieved by inhibition of K(+) channels)
      via Ca(v)2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of
      EPSC amplitude and charge compared with WT mice. Repetitive stimulation of
      afferent axons to the MNTB at different frequencies caused short-term depression
      of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice.
      Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM,
      pointing to enlarged residual calcium as a key factor in accelerating the
      replenishment of synaptic vesicles.

PMID- 22956803
TI  - 10 years of progress in chronic myelogenous leukemia.

PMID- 22956804
TI  - Don't give up - they eventually grow up: issues in AYA medicine.

PMID- 22956805
TI  - How NCCN guidelines can help young adults and older adolescents with cancer and
      the professionals who care for them.
AB  - From 1975 to 2009, adolescents and young adults with cancer in the United States
      had less mortality reduction and survival improvement than either children or
      older adults with cancer. An NCI Progress Review Group (PRG) convened in 2005
      issued a variety of recommendations to overcome the lack of progress, including
      the establishment of care guidelines. The outcome of 15- to 39-year-olds with
      cancer in the United States in 2009 was ascertained from the SEER registry, and
      the first guidelines for this age group, presented by NCCN, were reviewed. For
      the first time, the NCCN Clinical Practice Guidelines in Oncology (NCCN
      Guidelines) for Adolescent and Young Adult Oncology provide specific algorithm
      based care recommendations for 15- to 39-year-olds with cancer, who as an age
      group have the greatest potential patient-years of life to be saved. A special
      emphasis on psychosocial evaluation and care is included, commensurate with the
      unique needs of persons in this age group. Although how widely the NCCN
      Guidelines will be used remains to be seen, they are timely, comprehensive,
      responsive to the NCI PRG recommendations, and a valuable resource for medical
      oncologists, hematologists, gynecologic oncologists, oncologic surgeons, and
      pediatric oncologists who care for patients between 15 and 40 years of age. A
      patient version will have mutually beneficial effects for families and
      professionals.

PMID- 22956806
TI  - Metastatic mucinous ovarian cancer and treatment decisions based on histology and
      molecular markers rather than the primary location.
AB  - Approximately 22,000 cases of ovarian cancer occur each year in the United
      States, and likely fewer than 2000 cases of mucinous ovarian cancers. Although
      90% of patients with mucinous ovarian cancer present with stage I disease and
      have curative surgeries, advanced-stage disease is known to have a poor response
      to standard platinum- and taxane-based chemotherapy. Despite limited enthusiasm,
      standard chemotherapy is still recommended for most patients with advanced-stage
      mucinous malignancies of the ovary. This report presents an unusual case of a
      woman with HER2-positive metastatic mucinous carcinoma of the ovary treated with
      chemotherapy regimens typically used for colorectal malignancies, followed by
      epidermal growth factor receptor-targeted therapies.

PMID- 22956807
TI  - Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate
      Cancer provide multidisciplinary recommendations for the clinical management of
      patients with prostate cancer. These NCCN Guidelines Insights highlight notable
      recent updates. Abiraterone acetate is a first-in-class hormonal agent that
      represents a new standard of care for patients with metastatic castration
      recurrent prostate cancer who have previously received docetaxel (category 1
      recommendation). Abiraterone acetate also received category 2B recommendations in
      the prechemotherapy setting for asymptomatic patients or symptomatic patients who
      are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new
      indications for existing agents, including the option of sipuleucel-T as second
      line therapy. In addition, brachytherapy in combination with external beam
      radiation therapy with or without androgen deprivation therapy is now an
      alternative for patients with high-risk localized tumors or locally advanced
      disease.

PMID- 22956808
TI  - Androgen deprivation therapy: minimizing exposure and mitigating side effects.
AB  - Despite common and occasionally serious side effects, androgen deprivation
      therapy (ADT) is widely used in the management of prostate cancer at all stages
      and presentations. ADT is frequently used in situations in which evidence of
      benefit is lacking, such as combined with definitive radiotherapy for favorable
      risk prostate cancer, or in the primary management of elderly patients with low
      risk disease. In intermediate- and high-risk disease, the role of ADT is being
      challenged and is decreasing in importance, as the ability to deliver very high
      biologically effective doses becomes more widely available, especially through
      the combination of external radiotherapy and brachytherapy. Appropriately
      selecting patients for ADT according to established indications will minimize the
      number exposed, whereas systematic patient education before initiating treatment
      can ameliorate the side effects. Minimizing the exposure to ADT and efforts to
      mitigate the side effects may have a beneficial effect on quality of life for
      many men with prostate cancer.

PMID- 22956809
TI  - Enrollment criteria controversies for active surveillance and triggers for
      conversion to treatment in prostate cancer.
AB  - In the era of widespread prostate-specific antigen screening, low-risk and very
      low-risk prostate cancers are commonly identified, many of which will be of
      clinical insignificance. This has led to overtreatment and undue exposure to
      treatment-related morbidity in men harboring indolent tumors. Over the past 10
      years, active surveillance (AS) has been evolving as a management strategy for
      these cancers. With continual reevaluation, the intent is to definitively treat
      tumors that are clearly progressive before the window of opportunity for cure has
      closed. To date, many of the surveillance parameters are without validation of
      utility, variably used, and without a standardized schedule. However, new
      instruments for characterizing prostate cancer offer the potential to better
      distinguish which men are best managed definitively at the outset from those who
      would be better served with observation. The findings of currently available AS
      cohorts suggest that initial expectant management of early prostate cancer is
      reasonable, showing that only approximately 30% of observed tumors are
      reclassified to ones of intermediate risk with short-term follow-up. Prostate
      cancer survival for men undergoing AS is close to 100% in all available studies,
      but long-term data remain scarce for those requiring delayed curative therapy.

PMID- 22956810
TI  - Adolescent and young adult oncology. Clinical practice guidelines in oncology.
AB  - Cancer is the leading cause of death among the adolescent and young adult (AYA)
      population, excluding homicide, suicide, or unintentional injury. AYA patients
      should be managed by a multidisciplinary team of health care professionals who
      are well-versed in the specific developmental issues relevant to this patient
      population. The recommendations for age-appropriate care outlined in these NCCN
      Guidelines include psychosocial assessment, a discussion of infertility risks
      associated with treatment and options for fertility preservation, genetic and
      familial risk assessment for all patients after diagnosis, screening and
      monitoring of late effects in AYA cancer survivors after successful completion of
      therapy, and palliative care and end-of-life considerations for patients for whom
      curative therapy fails.

PMID- 22956811
TI  - Context for understanding psychosocial outcomes and behavior among adolescents
      and young adults with cancer.
AB  - Across all age groups, cancer affects relationships with family and friends;
      challenges one's sense of independence; disrupts goals, aspirations, and
      achievements; alters one's body image and integrity; and poses existential
      challenges about the world and one's place in it. When diagnosed with cancer,
      adolescents and young adults (AYAs) in their 20s and 30s face unique challenges
      compared with younger children and older adults. Understanding how cancer-related
      challenges manifest needs and desires for psychological and social support
      services throughout a continuum of care may help clinicians improve cost
      effective quality care and patient outcomes. This article provides a context for
      understanding the experiences of AYAs with cancer and highlights key domains of
      psychosocial need in this population.

PMID- 22956812
TI  - Hypofractionated whole breast radiation and partial breast radiation for early
      stage breast cancers: an update on progress.
AB  - This article provides an update of recent progress using partial breast
      irradiation (PBI) for the treatment of early-stage breast cancer, rather than
      whole breast radiotherapy (WBRT), which is the standard of care. Several large,
      prospective, randomized trials are nearing target accrual or have been completed,
      including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial,
      and the international TARGIT trial, and the status of each is discussed. The
      American Society for Radiation Oncology has also published a consensus statement
      to guide the use of PBI until some of the phase III trials are more mature.
      Finally, several articles have appeared recently, reporting unexpected adverse
      effects of PBI in small series, and this information is reviewed. Several recent
      prospective trials of WBRT are also discussed, with the theme of comparing the
      standard 25 fractions to a shortened, hypofractionated trial arm delivering
      equivalent doses of WBRT in approximately 15 treatments, another radiation
      strategy for a shortened course of treatment after breast-conserving surgery.

PMID- 22956813
TI  - Management of extramedullary leukemia as a presentation of acute myeloid
      leukemia.
AB  - Extramedullary involvement is considered to be an uncommon presentation of acute
      myeloid leukemia (AML), although some data suggest it may be present in up to 30%
      of patients. Extra-medullary involvement by AML can present in a variety of
      clinical manifestations, most notably in the form of myeloid sarcoma, leukemia
      cutis, and central nervous system involvement. Each presents a unique clinical
      scenario in terms of symptoms and management. Extramedullary disease in any form
      presenting without evidence of bone marrow disease is still considered evidence
      of systemic disease and is usually treated as such. Most commonly, extramedullary
      disease presents concurrently with bone marrow disease, and although it may
      require additional local therapy in the form of intrathecal chemotherapy or
      radiation, the principles of systemic treatment remain unchanged. The prognostic
      impact of extramedullary disease is unclear. Specifically, whether hematopoietic
      stem cell transplantation should be considered in first remission irrespective of
      other prognostic factors has not been established. Patients who undergo
      transplantation have similar outcomes as patients without extramedullary disease,
      although they do have a higher rate of extramedullary relapse. More research is
      needed to define the molecular basis for extramedullary disease, its prognostic
      impact, and optimal management.

PMID- 22956814
TI  - Communicating treatment options to older patients: challenges and opportunities.

PMID- 22956816
TI  - Antiphospholipase A2 receptor antibody titer and subclass in idiopathic
      membranous nephropathy.
AB  - The phospholipase A(2) receptor (PLA(2)R) is the major target antigen in
      idiopathic membranous nephropathy. The technique for measuring antibodies against
      PLA(2)R and the relationship between antibody titer and clinical characteristics
      are not well established. Here, we measured anti-PLA(2)R (aPLA(2)R) antibody
      titer and subclass in a well defined cohort of 117 Caucasian patients with
      idiopathic membranous nephropathy and nephrotic-range proteinuria using both
      indirect immunofluorescence testing (IIFT) and ELISA. We assessed agreement
      between tests and correlated antibody titer with clinical baseline parameters and
      outcome. In this cohort, aPLA(2)R antibodies were positive in 74% and 72% of
      patients using IIFT and ELISA, respectively. Concordance between both tests was
      excellent (94% agreement, kappa=0.85). Among 82 aPLA(2)R-positive patients,
      antibody titer significantly correlated with baseline proteinuria (P=0.02).
      Spontaneous remissions occurred significantly less frequently among patients with
      high antibody titers (38% versus 4% in the lowest and highest tertiles,
      respectively; P<0.01). IgG4 was the dominant subclass in the majority of
      patients. Titers of IgG4, but not IgG1 or IgG3, significantly correlated with the
      occurrence of spontaneous remission (P=0.03). In summary, these data show high
      agreement between IIFT and ELISA assessments of aPLA(2)R antibody titer and
      highlight the pathogenetic role of these antibodies, especially the IgG4
      subclass, given the observed relationships between aPLA(2)R titer, baseline
      proteinuria, and outcome.

PMID- 22956817
TI  - Urinary albumin: how low is normal?

PMID- 22956818
TI  - Nanoparticle-based test measures overall propensity for calcification in serum.
AB  - Vascular and soft tissue calcification contributes to cardiovascular morbidity
      and mortality in both the general population and CKD. Because calcium and
      phosphate serum concentrations are near supersaturation, the balance of
      inhibitors and promoters critically influences the development of calcification.
      An assay that measures the overall propensity for calcification to occur in serum
      may have clinical use. Here, we describe a nanoparticle-based assay that detects,
      in the presence of artificially elevated calcium and phosphate concentrations,
      the spontaneous transformation of spherical colloidal primary calciprotein
      particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics
      of this transition to describe the intrinsic capacity of serum to inhibit the
      precipitation of calcium and phosphate. Using this assay, we found that both the
      sera of mice deficient in fetuin-A, a serum protein that inhibits calcification,
      and the sera of patients on hemodialysis have reduced intrinsic properties to
      inhibit calcification. In summary, we developed a nanoparticle-based test that
      measures the overall propensity for calcification in serum. The clinical use of
      the test requires evaluation in a prospective study.

PMID- 22956819
TI  - Identification and characterization of an activating F229V substitution in the V2
      vasopressin receptor in an infant with NSIAD.
AB  - Gain-of-function mutations in the gene encoding the V2 vasopressin receptor (V2R)
      cause nephrogenic syndrome of inappropriate antidiuresis. To date, reported
      mutations lead to the substitution of arginine 137 by either a cysteine or
      leucine (R137C/L). Here, we describe a 3-month-old hyponatremic infant found to
      have a phenylalanine 229 to valine (F229V) substitution in V2R. Characterization
      of this substitution in vitro revealed that it leads to high constitutive
      activity of the receptor, compatible with spontaneous antidiuresis. In contrast
      to R137C/L mutant receptors, F229V receptors do not undergo spontaneous
      desensitization, which results in sustained, high basal activity. Notably, the
      V2R-selective inverse agonists tolvaptan and satavaptan completely silenced the
      constitutive signaling activity of the F229V mutant receptor, indicating that
      this substitution does not lock the receptor in an irreversible active state.
      Thus, inverse agonists might prove to be effective therapies for treating
      patients with this or other spontaneously activating mutations that do not lock
      the V2R in its active state. These results emphasize the importance of genetic
      testing and the functional characterization of mutant receptors for patients with
      nephrogenic syndrome of inappropriate antidiuresis because the results might
      inform treatment decisions.

PMID- 22956820
TI  - Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria.
AB  - The long-term outcome of patients with IgA nephropathy who present with normal
      renal function, microscopic hematuria, and minimal or no proteinuria is not well
      described. Here, we studied 141 Caucasian patients with biopsy-proven IgA
      nephropathy who had minor abnormalities at presentation and a median follow-up of
      108 months. None of the patients received corticosteroids or immunosuppressants.
      We reviewed renal biopsies using the Oxford classification criteria. In this
      sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary
      proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities
      were uncommon. Serum creatinine increases >50% and >100% were observed in five
      (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD.
      After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum
      creatinine values less than a 50% increase, respectively. Using Cox proportional
      hazards regression, the presence of segmental glomerulosclerosis was the only
      factor that significantly associated with a >50% increase in serum creatinine.
      Clinical remission occurred in 53 (37.5%) patients after a median of 48 months.
      Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients,
      respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41
      (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were
      hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59
      (41.8%) patients were treated with renin-angiotensin blockers because of
      hypertension or increasing proteinuria. In summary, the long-term prognosis for
      Caucasian patients with IgA nephropathy who present with minor urinary
      abnormalities and normal renal function is excellent.

PMID- 22956821
TI  - Narcolepsy: neural mechanisms of sleepiness and cataplexy.

PMID- 22956822
TI  - Therapeutic testosterone administration preserves excitatory synaptic
      transmission in the hippocampus during autoimmune demyelinating disease.
AB  - Over 50% of multiple sclerosis (MS) patients experience cognitive deficits, and
      hippocampal-dependent memory impairment has been reported in >30% of these
      patients. While postmortem pathology studies and in vivo magnetic resonance
      imaging demonstrate that the hippocampus is targeted in MS, the neuropathology
      underlying hippocampal dysfunction remains unknown. Furthermore, there are no
      treatments available to date to effectively prevent neurodegeneration and
      associated cognitive dysfunction in MS. We have recently demonstrated that the
      hippocampus is also targeted in experimental autoimmune encephalomyelitis (EAE),
      the most widely used animal model of MS. The objective of this study was to
      assess whether a candidate treatment (testosterone) could prevent hippocampal
      synaptic dysfunction and underlying pathology when administered in either a
      preventative or a therapeutic (postdisease induction) manner.
      Electrophysiological studies revealed impairments in basal excitatory synaptic
      transmission that involved both AMPA receptor-mediated changes in synaptic
      currents, and faster decay rates of NMDA receptor-mediated currents in mice with
      EAE. Neuropathology revealed atrophy of the pyramidal and dendritic layers of
      hippocampal CA1, decreased presynaptic (Synapsin-1) and postsynaptic
      (postsynaptic density 95; PSD-95) staining, diffuse demyelination, and microglial
      activation. Testosterone treatment administered either before or after disease
      induction restores excitatory synaptic transmission as well as presynaptic and
      postsynaptic protein levels within the hippocampus. Furthermore, cross-modality
      correlations demonstrate that fluctuations in EPSPs are significantly correlated
      to changes in postsynaptic protein levels and suggest that PSD-95 is a
      neuropathological substrate to impaired synaptic transmission in the hippocampus
      during EAE. This is the first report demonstrating that testosterone is a viable
      therapeutic treatment option that can restore both hippocampal function and
      disease-associated pathology that occur during autoimmune disease.

PMID- 22956823
TI  - Repeated stress dysregulates kappa-opioid receptor signaling in the dorsal raphe
      through a p38alpha MAPK-dependent mechanism.
AB  - Repeated stress releases dynorphins and causes subsequent activation of kappa
      opioid receptors (KORs) in limbic brain regions. The serotonergic dorsal raphe
      nucleus (DRN) has previously been found to be an important site of action for the
      dysphoric effects of dynorphin-kappa-opioid receptor system activation during
      stress-evoked behaviors, and KOR-induced activation of p38alpha mitogen-activated
      protein kinase (MAPK) in serotonergic neurons was found to be a critical mediator
      of the aversive properties of stress. Yet, how dynorphins and KORs functionally
      regulate the excitability of serotonergic DRN neurons both in adaptive and
      pathological stress states is poorly understood. Here we report that acute KOR
      activation by the selective agonist U69,593 [(+)-(5alpha,7alpha,8beta)-N-methyl-N
      [7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide] inhibits
      serotonergic neuronal excitability within the DRN through both presynaptic
      inhibition of excitatory synaptic transmission and postsynaptic activation of G
      protein-gated inwardly rectifying potassium channels (GIRKs)
      electrophysiologically recorded in brain slices. C57BL/6 mice subjected to
      repeated swim, stress sessions had significantly reduced KOR-mediated GIRK
      currents recorded in serotonergic neurons in DRN postsynaptically, without
      significantly affecting presynaptic KOR-mediated regulation of excitatory
      transmission. This effect was blocked by genetic excision of p38alpha MAPK
      selectively from serotonergic neurons. An increase in phospho-immunoreactivity
      suggests that this functional dysregulation may be a consequence of tyrosine
      phosphorylation of GIRK (K(IR)3.1) channels. These data elucidate a mechanism for
      stress-induced dysregulation of the excitability of neurons in the DRN and
      identify a functional target of stress-induced p38alpha MAPK activation that may
      underlie some of the negative effects of pathological stress exposure.

PMID- 22956824
TI  - Cholinergic coordination of presynaptic and postsynaptic activity induces timing
      dependent hippocampal synaptic plasticity.
AB  - Correlated presynaptic and postsynaptic activity is the key factor in inducing
      Hebbian plasticity and memory. However, little is known about the physiological
      events that could mediate such coordination. Correlated cholinergic input induces
      spike timing-dependent plasticity-like hippocampal synaptic plasticity.
      Cholinergic receptors are localized to both presynaptic and postsynaptic
      glutamatergic sites and thus have the potential to coordinate presynaptic and
      postsynaptic activity to induce plasticity. By directly monitoring presynaptic
      and postsynaptic activities with genetically encoded calcium indicators in mouse
      septohippocampal cocultures, we found interactive but independent presynaptic and
      postsynaptic modulations in the cholinergic-dependent synaptic plasticity.
      Neither presynaptic nor postsynaptic modulation alone is sufficient, but instead
      a coordinated modulation at both sites is required to induce the plasticity.
      Therefore, we propose that correlated cholinergic input can coordinate
      presynaptic and postsynaptic activities to induce timing-dependent synaptic
      plasticity, providing a novel mechanism by which neuromodulators precisely
      modulate network activity and plasticity with high efficiency and temporal
      precision.

PMID- 22956825
TI  - Flexible cortical control of task-specific muscle synergies.
AB  - Correlation structure in the activity of muscles across movements is often
      interpreted as evidence for low-level, hardwired constraints on upper-limb
      function. However, muscle synergies may also emerge from optimal strategies to
      achieve high-level task goals within a redundant control space. To distinguish
      these contrasting interpretations, we examined the structure of muscle
      variability during operation of a myoelectric interface in which task constraints
      were dissociated from natural limb biomechanics. We found that, with practice,
      human subjects learned to shape patterns of covariation between arbitrary pairs
      of hand and forearm muscles appropriately for elliptical targets whose
      orientation varied on a trial-by-trial basis. Thus, despite arriving at the same
      average location in the effector space, performance was improved by buffering
      variability into those dimensions that least impacted task success. Task
      modulation of beta-frequency intermuscular coherence indicated that differential
      recruitment of divergent corticospinal pathways contributed to positive
      correlations among muscles. However, this feedforward mechanism could not account
      for negative correlations observed in the presence of visual feedback. A second
      experiment revealed the development of fast, target-dependent visual responses
      consistent with "minimum intervention" control correcting predominantly task
      relevant errors. Together, these mechanisms contribute to the dynamic emergence
      of task-specific muscle synergies appropriate for a wide range of abstract task
      goals.

PMID- 22956826
TI  - Occipital transcranial magnetic stimulation has an activity-dependent suppressive
      effect.
AB  - The effects of transcranial magnetic stimulation (TMS) vary depending on the
      brain state at the stimulation moment. Four mechanisms have been proposed to
      underlie these effects: (1) virtual lesion--TMS suppresses neural signals; (2)
      preferential activation of less active neurons--TMS drives up activity in the
      stimulated area, but active neurons are saturating; (3) noise generation--TMS
      adds random neuronal activity, and its effect interacts with stimulus intensity;
      and (4) noise generation--TMS adds random neuronal activity, and its effect
      depends on TMS intensity. Here we explore these hypotheses by investigating the
      effects of TMS on early visual cortex by assessing the contrast response function
      while varying the adaptation state of the observers. We tested human participants
      in an orientation discrimination task, in which performance is contingent upon
      contrast sensitivity. Before each trial, neuronal activation of visual cortex was
      altered through contrast adaptation to two flickering gratings. In a factorial
      design, with or without adaptation, a single TMS pulse was delivered
      simultaneously with targets of varying contrast. Adaptation decreased contrast
      sensitivity. The effect of TMS on performance was state dependent: TMS decreased
      contrast sensitivity in the absence of adaptation but increased it after
      adaptation. None of the proposed mechanisms can account for the results in their
      entirety, in particular, for the facilitatory effect at intermediate to high
      contrasts after adaptation. We propose an alternative hypothesis: TMS effects are
      activity dependent, so that TMS suppresses the most active neurons and thereby
      changes the balance between excitation and inhibition.

PMID- 22956828
TI  - Adverse listening conditions and memory load drive a common alpha oscillatory
      network.
AB  - How does acoustic degradation affect the neural mechanisms of working memory?
      Enhanced alpha oscillations (8-13 Hz) during retention of items in working memory
      are often interpreted to reflect increased demands on storage and inhibition. We
      hypothesized that auditory signal degradation poses an additional challenge to
      human listeners partly because it draws on the same neural mechanisms. In an
      adapted Sternberg paradigm, auditory memory load and acoustic degradation were
      parametrically varied and the magnetoencephalographic response was analyzed in
      the time-frequency domain. Notably, during the stimulus-free delay interval,
      alpha power monotonically increased at central-parietal sensors as functions of
      memory load (higher alpha power with more memory load) and of acoustic
      degradation (also higher alpha power with more severe acoustic degradation). This
      alpha effect was superadditive when highest load was combined with most severe
      degradation. Moreover, alpha oscillatory dynamics during stimulus-free delay were
      predictive of response times to the probe item. Source localization of alpha
      power during stimulus-free delay indicated that alpha generators in right
      parietal, cingulate, supramarginal, and superior temporal cortex were sensitive
      to combined memory load and acoustic degradation. In summary, both challenges of
      memory load and acoustic degradation increase activity in a common alpha
      frequency network. The results set the stage for future studies on how chronic or
      acute degradations of sensory input affect mechanisms of executive control.

PMID- 22956827
TI  - Impact of prefrontal cortex in nicotine-induced excitation of ventral tegmental
      area dopamine neurons in anesthetized rats.
AB  - Systemic administration of nicotine increases dopaminergic (DA) neuron firing in
      the ventral tegmental area (VTA), which is thought to underlie nicotine reward.
      Here, we report that the medial prefrontal cortex (mPFC) plays a critical role in
      nicotine-induced excitation of VTA DA neurons. In chloral hydrate-anesthetized
      rats, extracellular single-unit recordings showed that VTA DA neurons exhibited
      two types of firing responses to systemic nicotine. After nicotine injection, the
      neurons with type-I response showed a biphasic early inhibition and later
      excitation, whereas the neurons with type-II response showed a monophasic
      excitation. The neurons with type-I, but not type-II, response exhibited
      pronounced slow oscillations (SOs) in firing. Pharmacological or structural mPFC
      inactivation abolished SOs and prevented systemic nicotine-induced excitation in
      the neurons with type-I, but not type-II, response, suggesting that these VTA DA
      neurons are functionally coupled to the mPFC and nicotine increases firing rate
      in these neurons in part through the mPFC. Systemic nicotine also increased the
      firing rate and SOs in mPFC pyramidal neurons. mPFC infusion of a non-alpha7
      nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the
      excitatory effect of systemic nicotine on the VTA DA neurons with type-I
      response, but mPFC infusion of nicotine failed to excite these neurons. These
      results suggest that nAChR activation in the mPFC is necessary, but not
      sufficient, for systemic nicotine-induced excitation of VTA neurons. Finally,
      systemic injection of bicuculline prevented nicotine-induced firing alterations
      in the neurons with type-I response. We propose that the mPFC plays a critical
      role in systemic nicotine-induced excitation of VTA DA neurons.

PMID- 22956829
TI  - The presynaptic active zone protein RIM1alpha controls epileptogenesis following
      status epilepticus.
AB  - To ensure operation of synaptic transmission within an appropriate dynamic range,
      neurons have evolved mechanisms of activity-dependent plasticity, including
      changes in presynaptic efficacy. The multidomain protein RIM1alpha is an integral
      component of the cytomatrix at the presynaptic active zone and has emerged as key
      mediator of presynaptically expressed forms of synaptic plasticity. We have
      therefore addressed the role of RIM1alpha in aberrant cellular plasticity and
      structural reorganization after an episode of synchronous neuronal activity
      pharmacologically induced in vivo [status epilepticus (SE)]. Post-SE, all animals
      developed spontaneous seizure events, but their frequency was dramatically
      increased in RIM1alpha-deficient mice (RIM1alpha(-/-)). We found that in wild
      type mice (RIM1alpha(+/+)) SE caused an increase in paired-pulse facilitation in
      the CA1 region of the hippocampus to the level observed in RIM1alpha(-/-) mice
      before SE. In contrast, this form of short-term plasticity was not further
      enhanced in RIM1alpha-deficient mice after SE. Intriguingly, RIM1alpha(-/-) mice
      showed a unique pattern of selective hilar cell loss (i.e., endfolium sclerosis),
      which so far has not been observed in a genetic epilepsy animal model, as well as
      less severe astrogliosis and attenuated mossy fiber sprouting. These findings
      indicate that the decrease in release probability and altered short- and long
      term plasticity as present in RIM1alpha(-/-) mice result in the formation of a
      hyperexcitable network but act in part neuroprotectively with regard to
      neuropathological alterations associated with epileptogenesis. In summary, our
      results suggest that presynaptic plasticity and proper function of RIM1alpha play
      an important part in a neuron's adaptive response to aberrant electrical
      activity.

PMID- 22956830
TI  - Rapamycin delays disease onset and prevents PrP plaque deposition in a mouse
      model of Gerstmann-Straussler-Scheinker disease.
AB  - Autophagy is a cell survival response to nutrient deprivation that delivers
      cellular components to lysosomes for digestion. In recent years, autophagy has
      also been shown to assist in the degradation of misfolded proteins linked to
      neurodegenerative disease (Ross and Poirier, 2004). In support of this,
      rapamycin, an autophagy inducer, improves the phenotype of several animal models
      of neurodegenerative disease. Our Tg(PrP-A116V) mice model Gerstmann-Straussler
      Scheinker disease (GSS), a genetic prion disease characterized by prominent
      ataxia and extracellular PrP amyloid plaque deposits in brain (Yang et al.,
      2009). To determine whether autophagy induction can mitigate the development of
      GSS, Tg(PrP-A116V) mice were chronically treated with 10 or 20 mg/kg rapamycin
      intraperitoneally thrice weekly, beginning at 6 weeks of age. We observed a dose
      related delay in disease onset, a reduction in symptom severity, and an extension
      of survival in rapamycin-treated Tg(PrP-A116V) mice. Coincident with this
      response was an increase in the autophagy-specific marker LC3II, a reduction in
      insoluble PrP-A116V, and a near-complete absence of PrP amyloid plaques in the
      brain. An increase in glial cell apoptosis of unclear significance was also
      detected. These findings suggest autophagy induction enhances elimination of
      misfolded PrP before its accumulation in plaques. Because ataxia persisted in
      these mice despite the absence of plaque deposits, our findings also suggest that
      PrP plaque pathology, a histopathological marker for the diagnosis of GSS, is not
      essential for the GSS phenotype.

PMID- 22956831
TI  - Ceftriaxone normalizes nucleus accumbens synaptic transmission, glutamate
      transport, and export following cocaine self-administration and extinction
      training.
AB  - Decreased basal glutamate levels are observed in the rat nucleus accumbens (NA)
      core following cocaine self-administration. This disruption of glutamate
      homeostasis arises from a reduction in the export of glutamate via system x(C)(-)
      and is accompanied by a decrease in expression of xCT, the catalytic subunit of
      system x(C)(-). A second hallmark of disrupted homeostasis is a decrease in
      expression and function of the major glutamate transporter, GLT-1. We have
      previously shown that chronic treatment with the antibiotic ceftriaxone restores
      xCT and GLT-1 expression following cocaine self-administration and attenuates
      both cue- and cocaine-primed reinstatement. Here we used a (3)H-glutamate uptake
      assay and microdialysis to test the hypothesis that ceftriaxone restores the
      function of both GLT-1 and xCT (glutamate reuptake and export, respectively) in
      the NA core following cocaine self-administration. We also used electrophysiology
      to investigate the ability of ceftriaxone to normalize measures of synaptic
      plasticity following cocaine. We found that 5 d of ceftriaxone treatment
      following cocaine self-administration restores basal glutamate levels in the
      accumbens core, likely through an upregulation of system x(C)(-) function. We
      also found that ceftriaxone restores glutamate reuptake and attenuates the
      increase in synaptically released glutamate that accompanies cocaine-primed
      reinstatement. Ceftriaxone also reversed the cocaine-induced synaptic
      potentiation in the accumbens core, evidenced by normalized spontaneous EPSC
      amplitude and frequency and evoked EPSC amplitude. These data indicate that
      ceftriaxone normalizes multiple aspects of glutamate homeostasis following
      cocaine self-administration and thus holds the potential to reduce relapse in
      human cocaine addicts.

PMID- 22956832
TI  - Gamma-band activity in human prefrontal cortex codes for the number of relevant
      items maintained in working memory.
AB  - Previous studies in electrophysiology have provided consistent evidence for a
      relationship between neural oscillations in different frequency bands and the
      maintenance of information in working memory (WM). While the amplitude and cross
      frequency coupling of neural oscillations have been shown to be modulated by the
      number of items retained during WM, interareal phase synchronization has been
      associated with the integration of distributed activity during WM maintenance.
      Together, these findings provided important insights into the oscillatory
      dynamics of cortical networks during WM. However, little is known about the
      cortical regions and frequencies that underlie the specific maintenance of
      behaviorally relevant information in WM. In the current study, we addressed this
      question with magnetoencephalography and a delayed match-to-sample task involving
      distractors in 25 human participants. Using spectral analysis and beamforming, we
      found a WM load-related increase in the gamma band (60-80 Hz) that was localized
      to the right intraparietal lobule and left Brodmann area 9 (BA9). WM-load related
      changes were also detected at alpha frequencies (10-14 Hz) in Brodmann area 6,
      but did not covary with the number of relevant WM-items. Finally, we decoded
      gamma-band source activity with a linear discriminant analysis and found that
      gamma-band activity in left BA9 predicted the number of target items maintained
      in WM. While the present data show that WM maintenance involves activity in the
      alpha and gamma band, our results highlight the specific contribution of gamma
      band delay activity in prefrontal cortex for the maintenance of behaviorally
      relevant items.

PMID- 22956833
TI  - Traumatic noise activates Rho-family GTPases through transient cellular energy
      depletion.
AB  - Small GTPases mediate transmembrane signaling and regulate the actin cytoskeleton
      in eukaryotic cells. Here, we characterize the auditory pathology of adult male
      CBA/J mice exposed to traumatic noise (2-20 kHz; 106 dB; 2 h). Loss of outer hair
      cells was evident 1 h after noise exposure in the basal region of the cochlea and
      spread apically with time, leading to permanent threshold shifts of 35, 60, and
      65 dB at 8, 16, and 32 kHz. Several biochemical and molecular changes correlated
      temporally with the loss of cells. Immediately after exposure, the concentration
      of ATP decreased in cochlear tissue and reached a minimum after 1 h while the
      immunofluorescent signal for p-AMPKalpha significantly increased in sensory hair
      cells at that time. Levels of active Rac1 increased, whereas those of active RhoA
      decreased significantly 1 h after noise attaining a plateau at 1-3 h; the
      formation of a RhoA-p140mDia complex was consistent with an activation of Rho
      GTPase pathways. Also at 1-3 h after exposure, the caspase-independent cell death
      marker, Endo G, translocated to the nuclei of outer hair cells. Finally,
      experiments with the inner ear HEI-OC1 cell line demonstrated that the energy
      depleting agent oligomycin enhanced both Rac1 activity and cell death. The sum of
      the results suggests that traumatic noise induces transient cellular ATP
      depletion and activates Rho GTPase pathways, leading to death of outer hair cells
      in the cochlea.

PMID- 22956834
TI  - Alleviation of neuropathic pain hypersensitivity by inhibiting neuronal pentraxin
      1 in the rostral ventromedial medulla.
AB  - Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia,
      and allodynia. Excitatory amino acid receptor-dependent increases in descending
      facilitatory drive from the brainstem rostral ventromedial medulla (RVM)
      contribute to injury-evoked hypersensitivity. Although increased excitability
      likely reflects changes in synaptic efficacy, the cellular mechanisms underlying
      injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1
      (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis
      and AMPA receptor recruitment to immature synapses. Its role in the adult brain
      and in descending pain facilitation is unknown. Here, we use the spared nerve
      injury (SNI) model in rodents to examine this issue. We show that SNI increases
      RVM NP1 expression and constitutive deletion or silencing NP1 in the RVM, before
      or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of
      RVM NP1 expression restores behavioral hypersensitivity of knock-out mice,
      demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.

PMID- 22956835
TI  - Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to
      histamine neurons in situ.
AB  - Hypothalamic hypocretin/orexin (hcrt/orx) neurons coordinate sleep-wake cycles,
      reward seeking, and body energy balance. Neurochemical data suggest that hcrt/orx
      cells contain several transmitters, but what hcrt/orx cells release onto their
      projection targets is unknown. A major pathway by which hcrt/orx neurons are
      thought to promote arousal is through projections to tuberomammillary histamine
      (HA) neurons. To study the impact of the electrical activity in hcrt/orx cells on
      HA neurons, we genetically targeted the light-activated excitatory ion channel
      channelrhodopsin-2 (ChR2) to the plasma membrane of hcrt/orx cells, and performed
      patch-clamp recordings from HA cells in acute mouse brain slices. Stimulation of
      ChR2-containing fibers with millisecond flashes of blue light produced fast
      postsynaptic currents in HA neurons, with a high connection probability (~60% of
      HA cells were connected to ~40% of hcrt/orx cells expressing ChR2). These inputs
      depended on tetrodotoxin-sensitive action potentials, had kinetics typical of
      glutamatergic responses mediated by AMPA receptors, were blocked by the AMPA
      receptor blocker CNQX, and displayed multiple forms of short-term plasticity
      (depression in ~70% trials, facilitation in ~30% trials, both often in the same
      cell). Furthermore, stimulation of hcrt/orx axons at physiological frequencies
      rapidly and reversibly increased action potential firing in HA cells, an effect
      that was abolished by blockade of AMPA receptors. These results provide the first
      functional evidence that hcrt/orx neurons are capable of fast glutamatergic
      control of their projection targets, and suggest that variations in electrical
      activity of hcrt/orx axons can induce rapid changes in long-range signals
      generated by HA neurons.

PMID- 22956836
TI  - Reward cues in space: commonalities and differences in neural coding by
      hippocampal and ventral striatal ensembles.
AB  - Forming place-reward associations critically depends on the integrity of the
      hippocampal-ventral striatal system. The ventral striatum (VS) receives a strong
      hippocampal input conveying spatial-contextual information, but it is unclear how
      this structure integrates this information to invigorate reward-directed
      behavior. Neuronal ensembles in rat hippocampus (HC) and VS were simultaneously
      recorded during a conditioning task in which navigation depended on path
      integration. In contrast to HC, ventral striatal neurons showed low spatial
      selectivity, but rather coded behavioral task phases toward reaching goal sites.
      Outcome-predicting cues induced a remapping of firing patterns in the HC,
      consistent with its role in episodic memory. VS remapped in conjunction with the
      HC, indicating that remapping can take place in multiple brain regions engaged in
      the same task. Subsets of ventral striatal neurons showed a "flip" from high
      activity when cue lights were illuminated to low activity in intertrial
      intervals, or vice versa. The cues induced an increase in spatial information
      transmission and sparsity in both structures. These effects were paralleled by an
      enhanced temporal specificity of ensemble coding and a more accurate
      reconstruction of the animal's position from population firing patterns.
      Altogether, the results reveal strong differences in spatial processing between
      hippocampal area CA1 and VS, but indicate similarities in how discrete cues
      impact on this processing.

PMID- 22956837
TI  - Characterization of Drosophila larval crawling at the level of organism, segment,
      and somatic body wall musculature.
AB  - Understanding rhythmic behavior at the developmental and genetic levels has
      important implications for neurobiology, medicine, evolution, and robotics. We
      studied rhythmic behavior--larval crawling--in the genetically and
      developmentally tractable organism, Drosophila melanogaster. We used narrow
      diameter channels to constrain behavior to simple, rhythmic crawling. We
      quantified crawling at the organism, segment, and muscle levels. We showed that
      Drosophila larval crawling is made up of a series of periodic strides. Each
      stride consists of two phases. First, while most abdominal segments remain
      planted on the substrate, the head, tail, and gut translocate; this "visceral
      pistoning" moves the center of mass. The movement of the center of mass is likely
      powered by muscle contractions in the head and tail. Second, the head and tail
      anchor while a body wall wave moves each abdominal segment in the direction of
      the crawl. These two phases can be observed occurring independently in embryonic
      stages before becoming coordinated at hatching. During forward crawls, abdominal
      body wall movements are powered by simultaneous contraction of dorsal and ventral
      muscle groups, which occur concurrently with contraction of lateral muscles of
      the adjacent posterior segment. During reverse crawls, abdominal body wall
      movements are powered by phase-shifted contractions of dorsal and ventral
      muscles; and ventral muscle contractions occur concurrently with contraction of
      lateral muscles in the adjacent anterior segment. This work lays a foundation for
      use of Drosophila larva as a model system for studying the genetics and
      development of rhythmic behavior.

PMID- 22956839
TI  - Predicting perceptual decision biases from early brain activity.
AB  - Perceptual decision making is believed to be driven by the accumulation of
      sensory evidence following stimulus encoding. More controversially, some studies
      report that neural activity preceding the stimulus also affects the decision
      process. We used a multivariate pattern classification approach for the analysis
      of the human electroencephalogram (EEG) to decode choice outcomes in a perceptual
      decision task from spatially and temporally distributed patterns of brain
      signals. When stimuli provided discriminative information, choice outcomes were
      predicted by neural activity following stimulus encoding; when stimuli provided
      no discriminative information, choice outcomes were predicted by neural activity
      preceding the stimulus. Moreover, in the absence of discriminative information,
      the recent choice history primed the choices on subsequent trials. A diffusion
      model fitted to the choice probabilities and response time distributions showed
      that the starting point of the evidence accumulation process was shifted toward
      the previous choice, consistent with the hypothesis that choice priming biases
      the accumulation process toward a decision boundary. This bias is reflected in
      prestimulus brain activity, which, in turn, becomes predictive of future
      decisions. Our results provide a model of how non-stimulus-driven decision making
      in humans could be accomplished on a neural level.

PMID- 22956838
TI  - Anatomical characterization of a rabbit cerebellar eyeblink premotor pathway
      using pseudorabies and identification of a local modulatory network in anterior
      interpositus.
AB  - Rabbit eyeblink conditioning is a well characterized model of associative
      learning. To identify specific neurons that are part of the eyeblink premotor
      pathway, a retrograde transsynaptic tracer (pseudorabies virus) was injected into
      the orbicularis oculi muscle. Four time points (3, 4, 4.5, and 5 d) were selected
      to identify sequential segments of the pathway and a map of labeled structures
      was generated. At 3 d, labeled first-order motor neurons were found in
      dorsolateral facial nucleus ipsilaterally. At 4 d, second-order premotor neurons
      were found in reticular nuclei, and sensory trigeminal, auditory, vestibular, and
      motor structures, including contralateral red nucleus. At 4.5 d, labeled third
      order premotor neurons were found in the pons, midbrain, and cerebellum,
      including dorsolateral anterior interpositus nucleus and rostral fastigial
      nucleus. At 5 d, labeling revealed higher-order premotor structures. Labeled
      fourth-order Purkinje cells were found in ipsilateral cerebellar cortex in
      cerebellar lobule HVI and in lobule I. The former has been implicated in eyeblink
      conditioning and the latter in vestibular control. Labeled neurons in anterior
      interpositus were studied, using neurotransmitter immunoreactivity to classify
      individual cell types and delineate their interconnectivity. Labeled third-order
      premotor neurons were immunoreactive for glutamate and corresponded to large
      excitatory projection neurons. Labeled fourth-order premotor interneurons were
      immunoreactive for GABA (30%), glycine (18%), or both GABA and glycine (52%) and
      form a functional network within anterior interpositus involved in modulation of
      motor commands. These results identify a complete eyeblink premotor pathway, deep
      cerebellar interconnectivity, and specific neurons responsible for the generation
      of eyeblink responses.

PMID- 22956840
TI  - A neural signature of affiliative emotion in the human septohypothalamic area.
AB  - Comparative studies have established that a number of structures within the
      rostromedial basal forebrain are critical for affiliative behaviors and social
      attachment. Lesion and neuroimaging studies concur with the importance of these
      regions for attachment and the experience of affiliation in humans as well. Yet
      it remains obscure whether the neural bases of affiliative experiences can be
      differentiated from the emotional valence with which they are inextricably
      associated at the experiential level. Here we show, using functional MRI, that
      kinship-related social scenarios evocative of affiliative emotion induce septal
      preoptic-anterior hypothalamic activity that cannot be explained by positive or
      negative emotional valence alone. Our findings suggest that a phylogenetically
      conserved ensemble of basal forebrain structures, especially the
      septohypothalamic area, may play a key role in enabling human affiliative
      emotion. Our finding of a neural signature of human affiliative experience bears
      direct implications for the neurobiological mechanisms underpinning impaired
      affiliative experiences and behaviors in neuropsychiatric conditions.

PMID- 22956841
TI  - Key electrophysiological, molecular, and metabolic signatures of sleep and
      wakefulness revealed in primary cortical cultures.
AB  - Although sleep is defined as a behavioral state, at the cortical level sleep has
      local and use-dependent features suggesting that it is a property of neuronal
      assemblies requiring sleep in function of the activation experienced during prior
      wakefulness. Here we show that mature cortical cultured neurons display a default
      state characterized by synchronized burst-pause firing activity reminiscent of
      sleep. This default sleep-like state can be changed to transient tonic firing
      reminiscent of wakefulness when cultures are stimulated with a mixture of waking
      neurotransmitters and spontaneously returns to sleep-like state. In addition to
      electrophysiological similarities, the transcriptome of stimulated cultures
      strikingly resembles the cortical transcriptome of sleep-deprived mice, and
      plastic changes as reflected by AMPA receptors phosphorylation are also similar.
      We used our in vitro model and sleep-deprived animals to map the metabolic
      pathways activated by waking. Only a few metabolic pathways were identified,
      including glycolysis, aminoacid, and lipids. Unexpectedly large increases in
      lysolipids were found both in vivo after sleep deprivation and in vitro after
      stimulation, strongly suggesting that sleep might play a major role in
      reestablishing the neuronal membrane homeostasis. With our in vitro model, the
      cellular and molecular consequences of sleep and wakefulness can now be
      investigated in a dish.

PMID- 22956842
TI  - Taurine release by astrocytes modulates osmosensitive glycine receptor tone and
      excitability in the adult supraoptic nucleus.
AB  - Cells can release the free amino acid taurine through volume-regulated anion
      channels (VRACs), and it has been hypothesized that taurine released from glial
      cells is capable of inhibiting action potential (AP) firing by activating
      neuronal glycine receptors (GlyRs) (Hussy et al., 1997). Although an inhibitory
      GlyR tone is widely observed in the brain, it remains unknown whether this
      specifically reflects gliotransmission because most neurons also express VRACs
      and other endogenous molecules can activate GlyRs. We found that VRACs are absent
      in neurons of the rat supraoptic nucleus (SON), suggesting that glial cells are
      the exclusive source of taurine in this nucleus. Application of strychnine to rat
      hypothalamic explants caused a depolarization of SON neurons associated with a
      decrease of chloride conductance and could excite these cells in the absence of
      fast synaptic transmission. This inhibitory GlyR tone was eliminated by
      pharmacological blockade of VRACs, by cellular taurine depletion, by metabolic
      inactivation of glia with fluorocitrate, and after retraction of astrocytic
      processes that intercalate neuronal somata and dendrites. Finally, GlyR tone
      varied inversely with extracellular fluid tonicity to mediate the osmotic control
      of AP firing by SON neurons. These findings establish taurine as a physiological
      gliotransmitter and show that gliotransmission is a spatially constrained process
      that can be modulated by the morphological rearrangement of astrocytes.

PMID- 22956843
TI  - Myelin gene regulatory factor is required for maintenance of myelin and mature
      oligodendrocyte identity in the adult CNS.
AB  - Although the transcription factors required for the generation of
      oligodendrocytes and CNS myelination during development have been relatively well
      established, it is not known whether continued expression of the same factors is
      required for the maintenance of myelin in the adult. Here, we use an inducible
      conditional knock-out strategy to investigate whether continued oligodendrocyte
      expression of the recently identified transcription factor myelin gene regulatory
      factor (MRF) is required to maintain the integrity of myelin in the adult CNS.
      Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted
      in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5
      weeks and peaking at 8 weeks after ablation of MRF. This demyelination was
      accompanied by microglial/macrophage infiltration and axonal damage. Transcripts
      for myelin genes, such as proteolipid protein, MAG, MBP, and myelin
      oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF,
      indicating an ongoing requirement for MRF in the expression of these genes.
      Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis
      over a period of weeks. Surviving oligodendrocytes gradually lose the expression
      of mature markers such as CC1 antigen and their association with myelin, without
      reexpressing oligodendrocyte progenitor markers or reentering the cell cycle.
      These results demonstrate that ongoing expression of MRF within the adult CNS is
      critical to maintain mature oligodendrocyte identity and the integrity of CNS
      myelin.

PMID- 22956845
TI  - Dynamics of local input normalization result from balanced short- and long-range
      intracortical interactions in area V1.
AB  - To efficiently drive many behaviors, sensory systems have to integrate the
      activity of large neuronal populations within a limited time window. These
      populations need to rapidly achieve a robust representation of the input image,
      probably through canonical computations such as divisive normalization. However,
      little is known about the dynamics of the corticocortical interactions
      implementing these rapid and robust computations. Here, we measured the real-time
      activity of a large neuronal population in V1 using voltage-sensitive dye imaging
      in behaving monkeys. We found that contrast gain of the population increases over
      time with a time constant of ~30 ms and propagates laterally over the cortical
      surface. This dynamic is well accounted for by a divisive normalization achieved
      through a recurrent network that transiently increases in size after response
      onset with a slow swelling speed of 0.007-0.014 m/s, suggesting a polysynaptic
      intracortical origin. In the presence of a surround, this normalization pool is
      gradually balanced by lateral inputs propagating from distant cortical locations.
      This results in a centripetal propagation of surround suppression at a speed of
      0.1-0.3 m/s, congruent with horizontal intracortical axons speed. We propose that
      a simple generalized normalization scheme can account for both the dynamical
      contrast response function through recurrent polysynaptic intracortical loops and
      for the surround suppression through long-range monosynaptic horizontal spread.
      Our results demonstrate that V1 achieves a rapid and robust context-dependent
      input normalization through a timely push-pull between local and lateral
      networks. We suggest that divisive normalization, a fundamental canonical
      computation, should be considered as a dynamic process.

PMID- 22956844
TI  - Sox21 promotes hippocampal adult neurogenesis via the transcriptional repression
      of the Hes5 gene.
AB  - Despite the importance of the production of new neurons in the adult hippocampus,
      the transcription network governing this process remains poorly understood. The
      High Mobility Group (HMG)-box transcription factor, Sox2, and the cell surface
      activated transcriptional regulator, Notch, play important roles in CNS stem
      cells. Here, we demonstrate that another member of the SoxB (Sox1/Sox2/Sox3)
      transcription factor family, Sox21, is also a critical regulator of adult
      neurogenesis in mouse hippocampus. Loss of Sox21 impaired transition of
      progenitor cells from type 2a to type 2b, thereby reducing subsequent production
      of new neurons in the adult dentate gyrus. Analysis of the Sox21 binding sites in
      neural stem/progenitor cells indicated that the Notch-responsive gene, Hes5, was
      a target of Sox21. Sox21 repressed Hes5 gene expression at the transcriptional
      level. Simultaneous overexpression of Hes5 and Sox21 revealed that Hes5 was a
      downstream effector of Sox21 at the point where the Notch and Sox pathways
      intersect to control the number of neurons in the adult hippocampus. Therefore,
      Sox21 controls hippocampal adult neurogenesis via transcriptional repression of
      the Hes5 gene.

PMID- 22956846
TI  - Elimination of dendritic spines with long-term memory is specific to active
      circuits.
AB  - Structural changes in brain circuits active during learning are thought to be
      important for long-term memory storage. If these changes support long-term
      information storage, they might be expected to be present at distant time points
      after learning, as well as to be specific to the circuit activated with learning,
      and sensitive to the contingencies of the behavioral paradigm. Here, we show such
      changes in the hippocampus as a result of contextual fear conditioning. There
      were significantly fewer spines specifically on active neurons of fear
      conditioned mice. This spine loss did not occur in homecage mice or in mice
      exposed to the training context alone. Mice exposed to unpaired shocks showed a
      generalized reduction in spines. These learning-related changes in spine density
      could reflect a direct mechanism of encoding or alternately could reflect a
      compensatory adaptation to previously described enhancement in transmission due
      to glutamate receptor insertion.

PMID- 22956847
TI  - Anoxia-induced NMDA receptor activation opens pannexin channels via Src family
      kinases.
AB  - Anoxic depolarization of pyramidal neurons results from a large inward current
      that is activated, in part, by excessive glutamate release during exposure to
      anoxia/ischemia. Pannexin-1 (Panx1) channels can be activated both by ischemia
      and NMDA receptors (NMDARs), but the mechanisms of Panx1 activation are unknown.
      We used whole-cell recordings to show that pharmacological inhibition or
      conditional genetic deletion of Panx1 strongly attenuates the anoxic
      depolarization of CA1 pyramidal neurons in acute brain slices from rats and mice.
      Anoxia or exogenous NMDA activated Src family kinases (SFKs), as measured by
      increased phosphorylation of SFKs at Y416. The SFK inhibitor PP2 prevented Src
      activation and Panx1 opening during anoxia. A newly developed interfering peptide
      that targets the SFK consensus-like sequence of Panx1 (Y308) attenuated the
      anoxic depolarization (AD) without affecting SFK activation. Importantly, the
      NMDAR antagonists, D-APV and R-CPP, attenuated AD currents carried by Panx1, and
      the combined application of D-APV and (10)panx (a Panx1 blocker) inhibited AD
      currents to the same extent as either blocker alone. We conclude that activation
      of NMDARs during anoxia/ischemia recruits SFKs to open Panx1, leading to
      sustained neuronal depolarizations.

PMID- 22956848
TI  - Robo2--slit and Dcc--netrin1 coordinate neuron axonal pathfinding within the
      embryonic axon tracts.
AB  - In the embryonic vertebrate brain, early born neurons establish highly
      stereotyped embryonic axonal tracts along which the neuronal interconnections
      form. To understand the mechanism underlying neuron axonal pathfinding within the
      embryonic scaffold of axon tracts, we studied zebrafish anterior dorsal
      telencephalic (ADt) neuron development. While previous studies suggest the ADt
      neuronal axons extend along a commissural tract [anterior commissure (AC)] and a
      descending ipsilateral tract [supraoptic tract (SOT)], it is unclear whether
      individual ADt neuronal axons choose specific projection paths at the
      intersection between the AC and the SOT. We labeled individual ADt neurons using
      a forebrain-specific promoter to drive expression of fluorescent proteins. We
      found the ADt axonal projection patterns were heterogeneous and correlated with
      their soma positions. Our results suggest that cell intrinsic differences along
      the dorsal ventral axis of the telencephalon regulate the axonal projection
      choices. Next, we determined that the guidance receptors roundabout2 (Robo2) and
      deleted in colorectal cancer (Dcc) were differentially expressed in the ADt
      neurons. We showed that knocking down Robo2 function by injecting antisense
      morpholino oligonucleotides abolished the ipsilateral SOT originating from the
      ADt neurons. Knocking down Dcc function did not prevent formation of the AC and
      the SOT. In contrast, the AC was specifically reduced when Netrin1 function was
      knocked down. Further mechanistic studies suggested that Robo2 responded to the
      repellent Slit signals and suppressed the attractive Netrin signals. These
      findings demonstrate how Robo2-Slit and Dcc-Netrin coordinate the axonal
      projection choices of the developing neurons in the vertebrate forebrain.

PMID- 22956849
TI  - GluN2B-containing NMDA receptors promote wiring of adult-born neurons into
      olfactory bulb circuits.
AB  - In the developing telencephalon, NMDA receptors (NMDARs) are composed of GluN1
      and GluN2B subunits. These "young" NMDARs set a brake on synapse recruitment in
      neurons of the neonatal cortex. The functional role of GluN2B for synapse
      maturation of adult-born granule cells (GCs) in the olfactory bulb has not been
      established and may differ from that of differentiating neurons in immature brain
      circuits with sparse activity. We genetically targeted GCs by sparse retroviral
      delivery in mouse subventricular zone that allows functional analysis of single
      genetically modified cells in an otherwise intact environment. GluN2B-deficient
      GCs did not exhibit impairment with respect to the first developmental milestones
      such as synaptogenesis, dendrite formation, and maturation of inhibitory synaptic
      inputs. However, GluN2B deletion prevented maturation of glutamatergic synaptic
      input. This severe impairment in synaptic development was associated with a
      decreased response to novel odors and eventually led to the demise of adult-born
      GCs. The effect of GluN2B on GC survival is subunit specific, since it cannot be
      rescued by GluN2A, the subunit dominating mature NMDAR function. Our observations
      indicate that, GluN2B-containing NMDARs promote synapse activation in adult-born
      GCs that integrate in circuits with high and correlated synaptic activity. The
      function of GluN2B-containing NMDARs on synapse maturation can thus be
      bidirectional depending on the environment.

PMID- 22956850
TI  - Improved sensorimotor performance via stochastic resonance.
AB  - Several studies about noise-enhanced balance control in humans support the
      hypothesis that stochastic resonance can enhance the detection and transmission
      in sensorimotor system during a motor task. The purpose of the present study was
      to extend these findings in a simpler and controlled task. We explored whether a
      particular level of a mechanical Gaussian noise (0-15 Hz) applied on the index
      finger can improve the performance during compensation for a static force
      generated by a manipulandum. The finger position was displayed on a monitor as a
      small white point in the center of a gray circle. We considered a good
      performance when the subjects exhibited a low deviation from the center of this
      circle and when the performance had less variation over time. Several levels of
      mechanical noise were applied on the manipulandum. We compared the performance
      between zero noise (ZN), optimal noise (ON), and high noise (HN). In all subjects
      (8 of 8) the data disclosed an inverted U-like graph between the inverse of the
      mean variation in position and the input noise level. In other words, the mean
      variation was significantly smaller during ON than during ZN or HN. The findings
      suggest that the application of a tactile-proprioceptive noise can improve the
      stability in sensorimotor performance via stochastic resonance. Possible
      explanations for this improvement in motor precision are an increase of the
      peripheral receptors sensitivity and of the internal stochastic resonance,
      causing a better sensorimotor integration and an increase in corticomuscular
      synchronization.

PMID- 22956851
TI  - Brefeldin A-inhibited guanine exchange factor 2 regulates filamin A
      phosphorylation and neuronal migration.
AB  - Periventricular heterotopia (PH) is a human malformation of cortical development
      associated with gene mutations in ADP-ribosylation factor guanine exchange factor
      2 (ARFGEF2 encodes for Big2 protein) and Filamin A (FLNA). PH is thought to
      derive from neuroependymal disruption, but the extent to which neuronal migration
      contributes to this phenotype is unknown. Here, we show that Arfgef2 null mice
      develop PH and exhibit impaired neural migration with increased protein
      expression for both FlnA and phosphoFlnA at Ser2152. Big2 physically interacts
      with FlnA and overexpression of phosphomimetic Ser2512 FLNA impairs neuronal
      migration. FlnA phosphorylation directs FlnA localization toward the cell
      cytoplasm, diminishes its binding affinity to actin skeleton, and alters the
      number and size of paxillin focal adhesions. Collectively, our results
      demonstrate a molecular mechanism whereby Big2 inhibition promotes phosphoFlnA
      (Ser2152) expression, and increased phosphoFlnA impairs its actin binding
      affinity and the distribution of focal adhesions, thereby disrupting cell
      intrinsic neuronal migration.

PMID- 22956853
TI  - Cocaine evokes projection-specific synaptic plasticity of lateral habenula
      neurons.
AB  - Addictive drugs share the ability to increase dopamine (DA) levels and trigger
      synaptic adaptations in the mesocorticolimbic system, two cellular processes
      engaged in the early stages of drug seeking. Neurons located in the lateral
      habenula (LHb) modulate the activity of DA neurons and DA release, and adaptively
      tune goal-directed behaviors. Whether synaptic modifications in LHb neurons occur
      upon drug exposure remains, however, unknown. Here, we assessed the influence of
      cocaine experience on excitatory transmission onto subsets of LHb neurons using a
      combination of retrograde tracing and ex vivo patch-clamp recordings in mice.
      Recent evidence demonstrates that AMPA receptors lacking the GluA2 subunit
      mediate glutamatergic transmission in LHb neurons. We find that cocaine
      selectively potentiates AMPA receptor-mediated EPSCs in LHb neurons that send
      axons to the rostromedial tegmental nucleus, a GABAergic structure that modulates
      the activity of midbrain DA neurons. Cocaine induces a postsynaptic accumulation
      of AMPA receptors without modifying their subunit composition or single-channel
      conductance. As a consequence, a protocol pairing presynaptic glutamate release
      with somatic hyperpolarization, to increase the efficiency of GluA2-lacking AMPA
      receptors, elicited a long-term potentiation in neurons only from cocaine-treated
      mice. This suggests that cocaine resets the rules for the induction of synaptic
      long-term plasticity in the LHb. Our study unravels an early, projection
      specific, cocaine-evoked synaptic potentiation in the LHb that may represent a
      permissive step for the functional reorganization of the mesolimbic system after
      drug exposure.

PMID- 22956852
TI  - Integration of beta-catenin, sirtuin, and FOXO signaling protects from mutant
      huntingtin toxicity.
AB  - One of the current challenges of neurodegenerative disease research is to
      determine whether signaling pathways that are essential to cellular homeostasis
      might contribute to neuronal survival and modulate the pathogenic process in
      human disease. In Caenorhabditis elegans, sir-2.1/SIRT1 overexpression protects
      neurons from the early phases of expanded polyglutamine (polyQ) toxicity, and
      this protection requires the longevity-promoting factor daf-16/FOXO. Here, we
      show that this neuroprotective effect also requires the DAF-16/FOXO partner bar
      1/beta-catenin and putative DAF-16-regulated gene ucp-4, the sole mitochondrial
      uncoupling protein (UCP) in nematodes. These results fit with a previously
      proposed mechanism in which the beta-catenin FOXO and SIRT1 proteins may together
      regulate gene expression and cell survival. Knockdown of beta-catenin enhanced
      the vulnerability to cell death of mutant-huntingtin striatal cells derived from
      the HdhQ111 knock-in mice. In addition, this effect was compensated by SIRT1
      overexpression and accompanied by the modulation of neuronal UCP expression
      levels, further highlighting a cross-talk between beta-catenin and SIRT1 in the
      modulation of mutant polyQ cytoxicity. Taken together, these results suggest that
      integration of beta-catenin, sirtuin and FOXO signaling protects from the early
      phases of mutant huntingtin toxicity.

PMID- 22956854
TI  - Porous inorganic-organic shape memory polymers.
AB  - Thermoresponsive shape memory polymers (SMPs) are a type of stimuli-sensitive
      materials that switch from a temporary shape back to their permanent shape upon
      exposure to heat. While the majority of SMPs have been fabricated in the solid
      form, porous SMP foams exhibit distinct properties and are better suited for
      certain applications, including some in the biomedical field. Like solid SMPs,
      SMP foams have been restricted to a limited group of organic polymer systems. In
      this study, we prepared inorganic-organic SMP foams based on the photochemical
      cure of a macromer comprised of inorganic polydimethylsiloxane (PDMS) segments
      and organic poly(epsilon-caprolactone) (PCL) segments, diacrylated PCL(40)-block
      PDMS(37)-block-PCL(40). To achieve tunable pore size with high interconnectivity,
      the SMP foams were prepared via a refined solvent-casting/particulate-leaching
      (SCPL) method. By varying design parameters such as degree of salt fusion,
      macromer concentration in the solvent and salt particle size, the SMP foams with
      excellent shape memory behavior and tunable pore size, pore morphology, and
      modulus were obtained.

PMID- 22956855
TI  - Evaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized Trial
      of Advanced Prostate Cancer.
AB  - We present new statistical analyses of data arising from a clinical trial
      designed to compare two-stage dynamic treatment regimes (DTRs) for advanced
      prostate cancer. The trial protocol mandated that patients were to be initially
      randomized among four chemotherapies, and that those who responded poorly were to
      be rerandomized to one of the remaining candidate therapies. The primary aim was
      to compare the DTRs' overall success rates, with success defined by the
      occurrence of successful responses in each of two consecutive courses of the
      patient's therapy. Of the one hundred and fifty study participants, forty seven
      did not complete their therapy per the algorithm. However, thirty five of them
      did so for reasons that precluded further chemotherapy; i.e. toxicity and/or
      progressive disease. Consequently, rather than comparing the overall success
      rates of the DTRs in the unrealistic event that these patients had remained on
      their assigned chemotherapies, we conducted an analysis that compared viable
      switch rules defined by the per-protocol rules but with the additional provision
      that patients who developed toxicity or progressive disease switch to a non
      prespecified therapeutic or palliative strategy. This modification involved
      consideration of bivariate per-course outcomes encoding both efficacy and
      toxicity. We used numerical scores elicited from the trial's Principal
      Investigator to quantify the clinical desirability of each bivariate per-course
      outcome, and defined one endpoint as their average over all courses of treatment.
      Two other simpler sets of scores as well as log survival time also were used as
      endpoints. Estimation of each DTR-specific mean score was conducted using inverse
      probability weighted methods that assumed that missingness in the twelve
      remaining drop-outs was informative but explainable in that it only depended on
      past recorded data. We conducted additional worst-best case analyses to evaluate
      sensitivity of our findings to extreme departures from the explainable drop-out
      assumption.

PMID- 22956856
TI  - Creating and validating GIS measures of urban design for health research.
AB  - Studies relating urban design to health have been impeded by the unfeasibility of
      conducting field observations across large areas and the lack of validated
      objective measures of urban design. This study describes measures for five
      dimensions of urban design - imageability, enclosure, human scale, transparency,
      and complexity - created using public geographic information systems (GIS) data
      from the US Census and city and state government. GIS measures were validated for
      a sample of 588 New York City block faces using a well-documented field
      observation protocol. Correlations between GIS and observed measures ranged from
      0.28 to 0.89. Results show valid urban design measures can be constructed from
      digital sources.

PMID- 22956857
TI  - Tuning PEG-DA hydrogel properties via solvent-induced phase separation (SIPS)().
AB  - Poly(ethylene glycol) diacrylate (PEG-DA) hydrogels are widely utilized to probe
      cell-material interactions and ultimately for a material-guided approach to
      tissue regeneration. In this study, PEG-DA hydrogels were fabricated via solvent
      induced phase separation (SIPS) to obtain hydrogels with a broader range of
      tunable physical properties including morphology (e.g. porosity), swelling and
      modulus (G'). In contrast to conventional PEG-DA hydrogels prepared from an
      aqueous precursor solution, the reported SIPS protocol utilized a dichloromethane
      (DCM) precursor solution which was sequentially photopolymerized, dried and
      hydrated. Physical properties were further tailored by varying the PEG-DA wt%
      concentration (5 wt%-25 wt%) and M(n) (3.4k and 6k g mol (-1)). SIPS produced PEG
      DA hydrogels with a macroporous morphology as well as increased G' values versus
      the corresponding conventional PEG-DA hydrogels. Notably, since the total
      swelling was not significantly changed versus the corresponding conventional PEG
      DA hydrogels, pairs or series of hydrogels represent scaffolds in which
      morphology and hydration or G' and hydration are uncoupled. In addition, PEG-DA
      hydrogels prepared via SIPS exhibited enhanced degradation rates.

PMID- 22956858
TI  - Castration-resistant prostate cancer: potential targets and therapies.
AB  - The treatment landscape for patients with castration-resistant prostate cancer
      (CRPC) is undergoing significant changes with the advent of new therapies and
      multidisciplinary efforts by scientists and clinicians. As activation of multiple
      molecular pathways in the neoplastic prostate makes it impossible for single
      target drugs to be completely effective in treating CRPC, this has led to
      combination therapy strategy, where several molecules involved in tumor growth
      and disease progression are targeted by a therapeutic regimen. In the present
      review, we provide an update on the molecular pathways that play an important
      role in the pathogenesis of CRPC and discuss the current wave of new treatments
      to combat this lethal disease.

PMID- 22956859
TI  - Subcutaneous immunoglobulin therapy: a new option for patients with primary
      immunodeficiency diseases.
AB  - Since the 1950s, replacement of immunoglobulin G using human immunoglobulin has
      been the standard treatment for primary immunodeficiency diseases with defects in
      antibody production. These patients suffer from recurrent and severe infections,
      which cause lung damage and shorten their life span. Immunoglobulins given
      intravenously (IVIG) every 3-4 weeks are effective in preventing serious
      bacterial infections and improving the quality of life for treated patients.
      Administration of immunoglobulin subcutaneously (SCIG) is equally effective in
      preventing infections and has a lower incidence of serious adverse effects
      compared to IVIG. The tolerability and acceptability of SCIG has been
      demonstrated in numerous studies showing improvements in quality of life and a
      preference for subcutaneous immunoglobulin therapy in patients with antibody
      deficiencies.

PMID- 22956860
TI  - The molecular profile of luminal B breast cancer.
AB  - Molecular profiling studies have found that estrogen receptor-positive (ER+)
      human breast cancers are comprised of at least two distinct diseases with
      differing biologies. With the advent of DNA microarrays, global gene expression
      patterns were used to define the luminal A and luminal B subtypes of ER+ breast
      cancer, with luminal B cancers showing a more aggressive phenotype including
      substantially worse outcomes in patients. The luminal B subtype designation could
      be considered a surrogate for those ER+ tumors having low progesterone receptors,
      high proliferation, high grade, and predicted poor response to hormone therapy.
      While they express estrogen receptors, luminal B cancers do not show a
      corresponding expression of estrogen-regulated genes, and may therefore rely upon
      alternative pathways for growth. At the molecular level, luminal B cancers appear
      dramatically distinct from luminal A cancers, at the levels of gene expression,
      gene copy, somatic mutation, and DNA methylation; luminal B cancers are also
      genetically and genomically altered to a greater extent than luminal A cancers.
      While, in the clinical setting, luminal B is typically regarded as an ER+,
      hormone-sensitive disease, more research is needed into how to better treat it.
      Comprehensive profiling initiatives, such as The Cancer Genome Atlas, have
      recently provided us a catalog of mutated or copy altered genes, from which new
      therapeutic targets could potentially be mined. Candidate pathways that might be
      targeted in luminal B include those involving growth factor receptors, including
      HER2 and EGFR, as well as PI3K/Akt/mTor.

PMID- 22956861
TI  - Natural material adsorbed onto a polymer to enhance immune function.
AB  - BACKGROUND: In this study, we produced poly(ethylene glycol) (PEG) microspheres
      of different sizes and adsorbing a medicinal plant mixture, and verified their
      effect in vitro on the viability, superoxide production, and bactericidal
      activity of phagocytes in the blood. METHODS: The medicinal plant mixture was
      adsorbed onto PEG microspheres and its effects were evaluated by flow cytometry
      and fluorescence microscopy. RESULTS: Adsorption of the herbal mixture onto the
      PEG microspheres was achieved and the particles were internalized by phagocytes.
      PEG microspheres bearing the adsorbed herbal mixture stimulated superoxide
      release, and activated scavenging and microbicidal activity in phagocytes. No
      differences in functional activity were observed when the phagocytes were not
      incubated with PEG microspheres bearing the adsorbed herbal mixture. CONCLUSION:
      This system may be useful for the delivery of a variety of medicinal plants and
      can confer additional protection against infection. The data reported here
      suggest that a polymer adsorbed with a natural product is a treatment alternative
      for enhancing immune function.

PMID- 22956862
TI  - Ingestion of BioCell Collagen((r)), a novel hydrolyzed chicken sternal cartilage
      extract; enhanced blood microcirculation and reduced facial aging signs.
AB  - Skin aging and its clinical manifestation is associated with altered molecular
      metabolism in the extracellular matrix of the dermis. In a pilot open-label
      study, we investigated the effect of a dietary supplement, BioCell Collagen((r))
      (BCC), which contains a naturally occurring matrix of hydrolyzed collagen type II
      and low-molecular-weight hyaluronic acid and chondroitin sulfate, in 26 healthy
      females who displayed visible signs of natural and photoaging in the face. Daily
      supplementation with 1 g of BCC for 12 weeks led to a significant reduction of
      skin dryness/scaling (76%, P = 0.002) and global lines/wrinkles (13.2%, P =
      0.028) as measured by visual/tactile score. Additionally, a significant increase
      in the content of hemoglobin (17.7%, P = 0.018) and collagen (6.3%, P = 0.002) in
      the skin dermis was observed after 6 weeks of supplementation. At the end of the
      study, the increase in hemoglobin remained significant (15%, P = 0.008), while
      the increase in collagen content was maintained, but the difference from baseline
      was not significant (3.5%, P = 0.134). This study provides preliminary data
      suggesting that dietary supplementation with BCC elicits several physiological
      events which can be harnessed to counteract natural photoaging processes to
      reduce visible aging signs in the human face. A controlled study is necessary to
      verify these observations.

PMID- 22956863
TI  - Oral administration of French maritime pine bark extract (Flavangenol((r)))
      improves clinical symptoms in photoaged facial skin.
AB  - BACKGROUND: French maritime pine bark extract (PBE) has gained popularity as a
      dietary supplement in the treatment of various diseases due to its polyphenol
      rich ingredients. Oligometric proanthocyanidins (OPCs), a class of bioflavonoid
      complexes, are enriched in French maritime PBE and have antioxidant and anti
      inflammatory activity. Previous studies have suggested that French maritime PBE
      helps reduce ultraviolet radiation damage to the skin and may protect human
      facial skin from symptoms of photoaging. To evaluate the clinical efficacy of
      French maritime PBE in the improvement of photodamaged facial skin, we conducted
      a randomized trial of oral supplementation with PBE. METHODS: One hundred and
      twelve women with mild to moderate photoaging of the skin were randomized to
      either a 12-week open trial regimen of 100 mg PBE supplementation once daily or
      to a parallel-group trial regimen of 40 mg PBE supplementation once daily.
      RESULTS: A significant decrease in clinical grading of skin photoaging scores was
      observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation
      regimens. A significant reduction in the pigmentation of age spots was also
      demonstrated utilizing skin color measurements. CONCLUSION: Clinically
      significant improvement in photodamaged skin could be achieved with PBE. Our
      findings confirm the efficacy and safety of PBE.

PMID- 22956865
TI  - Alteration patterns of trabecular bone microarchitectural characteristics induced
      by osteoarthritis over time.
AB  - Information regarding the alteration of trabecular bone microarchitecture, which
      is one of the important criteria to estimate bone condition, induced by
      osteoarthritis (OA) is sparse. The current study therefore aimed to identify and
      quantify patterns of alterations in trabecular bone microarchitectural
      characteristics at tibial epiphysis induced by OA using in vivo microcomputed
      tomography. Fourteen 8-week-old female Sprague Dawley rats were randomly divided
      into control (n = 7) and OA (n = 7) groups. Rats in the OA group were
      administered monoiodoacetate into the knee-joint cavity. The tibial joints were
      scanned by in vivo microcomputed tomography at 0, 4, and 8 weeks after
      administration. Two-way analysis of variance with Tukey's honestly significant
      difference post hoc test was carried out for statistical analyses. The results
      showed that patterns of alterations in the trabecular bone microarchitectural
      characteristics in the OA group were not different from those in the control
      group from 0 to 4 weeks (P > 0.05), but differed from 4 to 8 weeks (P < 0.05). In
      particular, both trabecular bone thickness and trabecular bone separation
      distributions over time (4-8 weeks) differed significantly (P < 0.05). These
      findings suggest that the patterns of bone microarchitecture changes brought
      about by OA should be periodically considered in the diagnosis and management of
      arthritic symptoms over time. Improved understanding of the alteration pattern on
      trabecular bone microarchitecture may assist in developing more targeted
      treatment interventions for OA.

PMID- 22956864
TI  - Dysphagia in the elderly: management and nutritional considerations.
AB  - Dysphagia is a prevalent difficulty among aging adults. Though increasing age
      facilitates subtle physiologic changes in swallow function, age-related diseases
      are significant factors in the presence and severity of dysphagia. Among elderly
      diseases and health complications, stroke and dementia reflect high rates of
      dysphagia. In both conditions, dysphagia is associated with nutritional deficits
      and increased risk of pneumonia. Recent efforts have suggested that elderly
      community dwellers are also at risk for dysphagia and associated deficits in
      nutritional status and increased pneumonia risk. Swallowing rehabilitation is an
      effective approach to increase safe oral intake in these populations and recent
      research has demonstrated extended benefits related to improved nutritional
      status and reduced pneumonia rates. In this manuscript, we review data describing
      age related changes in swallowing and discuss the relationship of dysphagia in
      patients following stroke, those with dementia, and in community dwelling
      elderly. Subsequently, we review basic approaches to dysphagia intervention
      including both compensatory and rehabilitative approaches. We conclude with a
      discussion on the positive impact of swallowing rehabilitation on malnutrition
      and pneumonia in elderly who either present with dysphagia or are at risk for
      dysphagia.

PMID- 22956866
TI  - Associations between functional ability and life satisfaction in the oldest old:
      results from the longitudinal population study Good Aging in Skane.
AB  - OBJECTIVES: To describe change in functional ability in the oldest-old population
      during 3 years and examine its relation to life satisfaction (LS). A total of 681
      individuals aged 78 and older from the population-based study Good Aging in Skane
      took part. METHODS: Functional ability was assessed using Sonn and Asberg's
      Activities of Daily Living (ADL) scale and related to LS assessed by Neugarten et
      al's Life Satisfaction Index A (LSI-A). RESULTS: Fifty-one percent of 87-93-year
      olds reported ADL decline during 3 years. Individuals reporting impaired ADL had
      a mean LSI-A value of 23.0 compared to 26.4 in those unchanged. ADL decline had a
      stronger negative effect on LS in the younger group (78-84 years), r = 0.207, P <
      0.001. In a multiple regression model, one score's decline in ADL capacity
      corresponded to 1.5 scores lower LS (P < 0.001). DISCUSSION: Effort put into
      keeping the oldest old on a high level of functional ability has the potential to
      maintain the LS of this population.

PMID- 22956867
TI  - Testosterone replacement therapy among elderly males: the Testim Registry in the
      US (TRiUS).
AB  - BACKGROUND: Testosterone levels naturally decline with age in men, often
      resulting in testosterone deficiency (hypogonadism). However, few studies have
      examined hypogonadal characteristics and treatment in older (>=65 years) men.
      OBJECTIVE: To compare data at baseline and after 12 months of testosterone
      replacement therapy (TRT) in hypogonadal men >=65 vs <65 years old. Data for
      participants 65-74 vs >=75 years old were also compared. METHODS: Data were from
      TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men
      treated with Testim((r)) 1% (50-100 mg testosterone gel/day) for the first time.
      Anthropometric, laboratory, and clinical measures were taken at baseline and 12
      months, including primary outcomes of total testosterone (TT), free testosterone
      (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were
      made using Fisher's exact test or analysis of variance. Nonparametric Spearman's
      rho and first-order partial correlation coefficients adjusted for the effect of
      age were used to examine bivariate correlations among parameters. RESULTS: Of the
      registry participants at baseline with available age information, 16% (133/845)
      were >=65 years old. They were similar to men <65 years old in the duration of
      hypogonad-ism prior to enrollment (~1 year), TT and FT levels at baseline, TT and
      FT levels at 12-month follow-up, and in reported compliance with treatment. Older
      patients were more likely to receive lower doses of TRT. PSA levels did not
      statistically differ between groups after 12 months of TRT (2.18 +/- 2.18 ng/mL
      for >=65 vs 1.14 +/- 0.84 ng/mL for <65 years old, P = 0.1). Baseline values for
      the >75-year-old subcohort were not significantly different from subcohorts aged
      65-74 years and <65 years. CONCLUSION: Hypogonadal men >=65 years old showed
      significant benefit from TRT over 12 months, similar to that found for
      hypogonadal men <65 years old. TRT was well tolerated in older patients,
      successfully increased testosterone level regardless of age, and did not
      significantly increase PSA levels in older men.

PMID- 22956868
TI  - Preparation and in vitro studies of MRI-specific superparamagnetic iron oxide
      antiGPC3 probe for hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to develop an antiGPC3
      ultrasuperparamagnetic iron oxide (USPIO) probe for early detection of
      hepatocellular carcinoma. METHODS: GPC3 and AFP receptors were selected as
      biomarkers and conjugated with USPIO nanoparticles coated by dextran with
      carboxylate groups to synthesize antiGPC3-USPIO and antiAFP-USPIO probes. HepG2
      cells (a human hepatocellular carcinoma cell model with high expression of GPC3)
      were used along with SMMC-7721 cells (a hepatocellular carcinoma cell model with
      no expression of GPC3), HeLa cells (a cervical cancer model), and HL-7702 (normal
      hepatocytes) which were used as controls. After incubation with the probes, the
      iron content in the cells was calculated, USPIO nanoparticles in cells were
      observed using transmission electron microscopy, and T1 and T2 relaxation times
      were measured with a 1.5 T magnetic resonance scanner. RESULTS: AntiGPC3-USPIO
      probes with a mean hydrodynamic diameter of 47 nm showed good biological
      compatibility. Transmission electron microscopic images indicated that the amount
      of USPIO nanoparticles taken up was significantly higher in HepG2 cells incubated
      with antiGPC3-USPIO than that in HepG2 cells incubated with antiAFP-USPIO or
      USPIO nanoparticles and that in the SMMC-7721 or HeLa cells incubated with
      antiGPC3-USPIO probes, antiAFP-USPIO probes, or USPIO nanoparticles. The higher
      the concentration and the longer the incubation time, the greater the number of
      USPIO nanoparticles found in the cells. No USPIO nanoparticles were found in the
      HL-7702 cells. All of the HepG2, SMMC-7721, and HeLa cells incubated with
      antiGPC3-USPIO, antiAFP-USPIO, or USPIO nanoparticles were able to shorten the T1
      and T2 values in agar solution, especially the T2 images of HepG2 cells incubated
      with antiGPC3-USPIO probes. CONCLUSION: AntiGPC3-USPIO probes can be utilized as
      a specific magnetic resonance targeting contrast agent for early detection of
      hepatocellular carcinoma. Using a 1.5 T magnetic resonance scanner, the optimal
      time for imaging HepG2 cells was around 2-4 hours after incubation with antiGPC3
      USPIO probes.

PMID- 22956870
TI  - Wound-healing effect of micronized sacchachitin (mSC) nanogel on corneal
      epithelium.
AB  - The extraction residue of the Ganoderma fruiting body, named sacchachitin, has
      been demonstrated to have the potential to enhance cutaneous wound healing by
      inducing cell proliferation. In this study, a nanogel formed from micronized
      sacchachitin (mSC) was investigated for the potential treatment of superficial
      chemical corneal burns. Reportedly, mSC has been produced successfully and its
      chemical properties confirmed, and physical and rheological properties
      characterized. An in vitro cell proliferation study has revealed that at the
      concentrations of 200, 300, and 400 microg/mL, mSC nanogel significantly
      increased Statens Seruminstitut rabbit corneal (SIRC) cell proliferation after 24
      hours of incubation. In cell migration assay, migration of SIRC cell to wound
      closure was observed after 24 hours of incubation with the addition of 200
      microg/mL mSC of nanogel. In an animal study, acceleration of corneal wound
      healing was probably due to the inhibition of proteolysis. In conclusion, the
      findings of this study substantiate the potential application of sacchachitin in
      the form of mSC nanogel for the treatment of superficial corneal injuries.

PMID- 22956869
TI  - Nanotheranostics--a review of recent publications.
AB  - Theranostics is referred to as a treatment strategy that combines therapeutics
      with diagnostics, aiming to monitor the response to treatment and increase drug
      efficacy and safety, which would be a key part of personalized medicine and
      require considerable advances in predictive medicine. Theranostics associates
      with both a diagnosis that tests patients for possible reactions to taking new
      medication and targeted drug delivery based on the test results. Emerging
      nanotechnology provides a great deal of opportunity to design and develop such
      combination agents, permitting the delivery of therapeutics and concurrently
      allowing the detection modality to be used not only before or after but also
      throughout the entire treatment regimen. The introduction of nanotheranostics
      into routine health care has still a long way to go, since evaluations on
      cytotoxicity, genotoxicity, and immunotoxicity of prospective nanotheranostics,
      demonstration of cost-effectiveness, and availability of appropriate accessible
      testing systems are still required. An extensive review, from a chemistry point
      of view, of the recent development of nanotheranostics and its in vitro and in
      vivo applications are herein presented.

PMID- 22956871
TI  - Towards real-time detection of tumor margins using photothermal imaging of immune
      targeted gold nanoparticles.
AB  - BACKGROUND: One of the critical problems in cancer management is local recurrence
      of disease. Between 20% and 30% of patients who undergo tumor resection surgery
      require reoperation due to incomplete excision. Currently, there are no validated
      methods for intraoperative tumor margin detection. In the present work, we
      demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast
      agent for photothermal molecular imaging of cancer. METHODS: Phantoms containing
      different concentrations of GNPs were irradiated with continuous-wave laser and
      measured with a thermal imaging camera which detected the temperature field of
      the irradiated phantoms. RESULTS: The results clearly demonstrate the ability to
      distinguish between cancerous cells specifically targeted with GNPs and normal
      cells. This technique, which allows highly sensitive discrimination between
      adjacent low GNP concentrations, will allow tumor margin detection while the
      temperature increases by only a few degrees Celsius (for GNPs in relevant
      biological concentrations). CONCLUSION: We expect this real-time intraoperative
      imaging technique to assist surgeons in determining clear tumor margins and to
      maximize the extent of tumor resection while sparing normal background tissue.

PMID- 22956872
TI  - Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy.
AB  - BACKGROUND: Recently, nanoparticles have been demonstrated to have tremendous
      merit in terms of improving the treatment specificity and thermal ablation effect
      on tumors. However, the potential toxicity and long-term side effects caused by
      the introduced nanoparticles and by expelling them out of the body following
      surgery remain a significant challenge. Here, we propose for the first time to
      directly adopt magnesium nanoparticles as the heating enhancer in laser thermal
      ablation to avoid these problems by making full use of the perfect biodegradable
      properties of this specific material. METHODS: To better understand the new nano
      "green" hyperthermia modality, we evaluated the effects of magnesium
      nanoparticles on the temperature transients inside the human body subject to
      laser interstitial heating. Further, we experimentally investigated the heating
      enhancement effects of magnesium nanoparticles on a group of biological samples:
      oil, egg white, egg yolk, in vitro pig tissues, and the in vivo hind leg of
      rabbit when subjected to laser irradiation. RESULTS: Both the theoretical
      simulations and experimental measurements demonstrated that the target tissues
      injected with magnesium nanoparticles reached much higher temperatures than
      tissues without magnesium nanoparticles. This revealed the enhancing behavior of
      the new nanohyperthermia method. CONCLUSION: Given the unique features of
      magnesium nanoparticles--their complete biological safety and ability to enhance
      heating--which most other advanced metal nanoparticles do not possess, the use of
      magnesium nanoparticles in hyperthermia therapy offers an important "green"
      nanomedicine modality for treating tumors. This method has the potential to be
      used in clinics in the near future.

PMID- 22956873
TI  - Long-term tolerability of once-monthly injectable paliperidone palmitate in
      subjects with recently diagnosed schizophrenia.
AB  - BACKGROUND: A post hoc analysis from a multiphase trial with open-label
      transition and maintenance phases, a double-blind relapse prevention phase, and
      an optional open-label extension examined the long-term tolerability with
      continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg
      (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with
      recently diagnosed (<=5 years; n = 216) versus chronic illness (>5 years; n =
      429) schizophrenia. METHODS: Adverse events reported at a >=2% margin between
      subgroups were identified. Relative risks (in the recently diagnosed compared
      with the chronically ill) and 95% confidence intervals (CI) were determined, and
      CI not including 1 were considered potentially significant. RESULTS: In both
      subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean
      exposures were 333.9 +/- 271.9 and 308.7 +/- 278.3 days in the recently diagnosed
      and chronic illness subgroups, respectively. Using the criteria outlined in the
      methods, nasopharyngitis was a potentially significant event reported in more
      chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint
      (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8%
      versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus
      0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially
      significant events in more recently diagnosed than chronically ill subjects. Mean
      weight changes, sedation/somnolence, any extrapyramidal symptom-related or
      glucose-related events were generally similar between the groups. The mean
      prolactin level increased in both sexes in both subgroups (changes from baseline
      of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females
      and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males,
      respectively), and were higher in females with recently diagnosed illness than in
      females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related
      events were reported by 7.9% of recently diagnosed subjects with schizophrenia
      and 3.5% of those who were chronically ill. CONCLUSION: The long-term
      tolerability of paliperidone palmitate was generally similar in recently
      diagnosed schizophrenia subjects and those with more chronic illness, with the
      exception of some prolactin-related measures.

PMID- 22956875
TI  - Treatment options for postmenopausal osteoporosis.

PMID- 22956874
TI  - Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to
      progressive weakness from loss of motor neurons and death on average in less than
      3 years after symptom onset. No clear causes have been found and just one
      medication, riluzole, extends survival. Researchers have identified some of the
      cellular processes that occur after disease onset, including mitochondrial
      dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation,
      and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration
      or occur secondary to other cellular processes, and may itself contribute to
      oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to
      slow disease progression by testing drugs that impact one or more of these
      pathways. While every agent tested in the 18 years after the approval of riluzole
      has been ineffective, basic and clinical research methods in ALS have become
      dramatically more sophisticated. Dexpramipexole (RPPX), the R(+) enantiomer of
      pramiprexole, which is approved for symptomatic treatment of Parkinson disease,
      carries perhaps the currently largest body of pre-and early clinical data that
      support testing in ALS. The neuroprotective properties of RPPX in various models
      of neurodegeneration, including the ALS murine model, may be produced through
      protective actions on mitochondria. Early phase trials in human ALS suggest that
      the drug can be taken safely by patients in doses that provide neuroprotection in
      preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is
      underway.

PMID- 22956876
TI  - Efficacy of serum chitotriosidase activity in early treatment of patients with
      active tuberculosis and a negative sputum smear.
AB  - BACKGROUND: The results of sputum culture for Mycobacterium tuberculosis must be
      awaited in most cases, which delays the start of treatment in patients with
      sputum smear-negative pulmonary tuberculosis. We investigated whether plasma
      chitotriosidase activity is a strong marker for early diagnosis of tuberculosis
      in patients for whom a bacillus smear is negative and tuberculosis culture is
      positive. METHODS: Clinical, radiological, and laboratory features were evaluated
      in 75 patients, 17 of whom were diagnosed as having active tuberculosis by
      negative acid-fast bacillus smear and positive culture, 38 as having sequel
      tuberculosis which was radiologically and microbiologically negative, and 20 who
      served as healthy controls. Serum chitotriosidase activity levels were measured
      in both cases and controls. RESULTS: The mean age of the cases with active
      pulmonary tuberculosis, cases with sequel lesions, and controls was 23 +/- 2.4
      years, 22 +/- 1.7 years, and 24 +/- 2.1 years, respectively. Serum
      chitotriosidase levels were 68.05 +/- 72.61 nmol/hour/mL in smear-negative,
      culture-positive pulmonary tuberculosis cases (Group A) and 29.73 +/- 20.55
      nmol/hour/mL in smear-negative, culture-negative sequel pulmonary tuberculosis
      cases (Group B). Serum chitotriosidase levels from patients in Group A were
      significantly higher than in Group B and Group C. There was no statistically
      significant difference in serum chitotriosidase levels between cases with sequel
      pulmonary tuberculosis (Group B, smear-negative, culture-negative) and healthy
      controls (Group C). CONCLUSION: In patients with active tuberculosis and a
      negative sputum smear for acid-fast bacillus, plasma chitotriosidase activity
      seems to be a strong marker for diagnosis of active disease which can be used
      while awaiting culture results.

PMID- 22956877
TI  - Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria
      type 1.
AB  - BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by progressive
      renal insufficiency culminating in end-stage renal disease, and a wide range of
      clinical features related to systemic oxalosis in different organs. It is caused
      by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a
      defect in AGXT gene. CASE REPORT: Two brothers (one 6 months old; the other 2
      years old) presented with acute renal failure and urinary tract infection
      respectively. PH1 was confirmed by high urinary oxalate level, demonstration of
      oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene
      mutation. Despite the same genetic background, same sex, and shared environment,
      the outcome of the two siblings differs widely. While one of them died earlier
      with end-stage renal disease and multiorgan failure caused by systemic oxalosis,
      the older brother is pyridoxine responsive with normal development and renal
      function. CONCLUSION: Clinicians should be aware of extreme intrafamilial
      variability of PH1 and international registries are needed to characterize the
      genotype-phenotype correlation in such disorder.

PMID- 22956878
TI  - Ethnicity and acute myocardial infarction: risk profile at presentation, access
      to hospital management, and outcome in Norway.
AB  - BACKGROUND: Previous studies in North America have shown ethnic variation in the
      presentation of acute myocardial infarction (AMI), and sex and racial differences
      in the management and outcome of AMI. In the present study, our aim was to
      investigate the risk profile of AMI for patients with minority background
      compared with indigenous Norwegians, at hospital presentation, and to investigate
      racial differences in hospital care and outcomes. PATIENTS AND METHODS: A dual
      design study was adopted: a cross-sectional study to examine ethnic differences
      of risk prevalence at hospital presentation and a cohort study to estimate access
      to angiography, percutaneous coronary intervention (PCI), and hospital and long
      term mortality. From a study population of 3105 patients with AMI presenting at
      Oslo University Hospital between January 1, 2006 and December 31, 2007, we
      identified 147 cases of AMI in patients with minority background and selected a
      random sample of 588 indigenous Norwegians with AMI as controls. Prognostic and
      explanatory strategies were used in the analysis. RESULTS: Compared with
      indigenous Norwegians with AMI, AMI patients with minority background suffered
      their AMI 10 years younger, were generally male, were twice as likely to be
      smokers, three times as likely to have type 2 diabetes, had lower high-density
      lipoprotein levels. This group also had 50% less history of hypertension. In
      terms of hospital care, AMI patients with minority background had shorter times
      from onset of symptoms to PCI and the same frequency of access to angiography and
      acute PCI as indigenous Norwegians when adjusting for the confounding effect of
      age, sex, and nature of myocardial infarction with or without ST elevation.
      CONCLUSION: At presentation to hospital, patients with minority background had a
      higher risk profile and a shorter time from onset of symptoms to admission to
      catheterization laboratory than indigenous Norwegians, but the same access to
      angiography and acute PCI during hospitalization.

PMID- 22956879
TI  - Investigation of Borrelia burgdorferi genotypes in Australia obtained from
      erythema migrans tissue.
AB  - BACKGROUND: Lyme disease (LD) is an emerging infectious disease in Australia.
      There has been controversy regarding endemic lyme disease in the country for over
      20 years. Borrelia burgdorferi sensu stricto (Bbss) and sensu lato (Bbsl) are
      closely related spirochetal species that are the causative agents of LD in
      humans. Clinical transmission of this tick-borne disease is marked by a
      characteristic rash known as erythema migrans (EM). This study employed molecular
      techniques to demonstrate the spirochetal agent of Lyme disease isolated from EM
      biopsies of patients in Australia and then investigate their genetic diversity.
      METHODS: Four patients who presented to the author's practice over a one-year
      period from mid 2010 to mid 2011 returned positive results on central tissue
      biopsy of EM lesions using polymerase chain reaction (PCR) analysis. The findings
      were confirmed by DNA sequencing, and basic local alignment search tool (BLAST)
      analysis was then used to genetically characterize the causative organisms.
      RESULTS: Three isolates were identified as Bbss that lay genotypically between
      strains B31 and ZS7 and were then characterized as strain 64b. One of the three
      isolates though may have similarity to B. bissettii a Bbsl. The fourth isolate
      was more appropriately placed in the sensu lato group and appeared to be similar,
      but not identical to, a B. valaisiana-type isolate. In this study, a central
      biopsy taken within 6 days of infection was used instead of conventional sampling
      at the leading edge, and the merits of this are discussed. CONCLUSION: These
      patients acquired infection in Australia, further proving endemic LD on the
      continent. Central biopsy site of EM is a useful tool for PCR evaluation. BLAST
      searches suggest a genetic diversity of B. burgdorferi, which has implications
      concerning the diagnosis, clinical severity, and testing of LD in Australia.

PMID- 22956880
TI  - Objective and subjective in vivo comparison of two emollient products.
AB  - BACKGROUND: Few studies have directly compared the effectiveness of different
      emollients in vivo, and the important matter of patient preference is generally
      overlooked. METHODS: We report the results of an assessor-blinded, bilateral,
      concurrent comparison of two emollient pharmaceutical presentations, ie,
      Doublebase gel (DB) and Aqueous cream BP (AC), applied by 20 participants three
      times daily for 7 consecutive days. The primary efficacy endpoint was cumulative
      improvement in skin hydration measured by corneometry on days 1, 3, and 5
      immediately before the first application and approximately 2 hours after the
      third application of the day. Secondary endpoints were investigator assessment of
      skin condition at these time points and participant assessment of product
      acceptability at the end of the study. RESULTS: Both products increased skin
      hydration, but the effect of AC was relatively modest, with morning values
      readily returning to pretreatment levels. Hydration levels were higher for DB
      gel, maintained at all time points, and showed stepwise, cumulative increases
      over the 7 days of use. Overall patient satisfaction scores were higher for DB
      gel, and especially for "consistency," "ease of use," and "ease of absorption
      into the skin." Eighty-five percent of participants expressed a desire to use DB
      gel again as compared with 40% for AC.

PMID- 22956881
TI  - "Home of Younger Skin" (HOYS) program: Defining the change in apparent skin age
      after facial treatment with botulinum toxin and dermal fillers.
AB  - BACKGROUND: Objective and subjective scales estimating improvement in both
      clinical studies and clinical practice are becoming more mainstream. However, the
      use of a system to analyze improvement in aging with a multiplicity of treatments
      would be useful. The purpose of this study was to use a recently developed
      educative and patient self-assessment program ("Home of Younger Skin", HOYS) for
      assessment of the effect of facial treatment with neurotoxins and filling agents
      in terms of decreasing apparent age. METHODS: Four patients underwent facial
      treatments with neurotoxins and dermal fillers by an experienced blinded
      physician and were assessed twice utilizing an age analysis program (HOYS), once
      before and then 6 weeks after completion of treatment. RESULTS: The four patients
      showed an average reduction in apparent facial age of 7.5 years. The individual
      "regions" differed in their reductions. The upper face showed a decline of 13.5
      years, the periorbital region 9.25 years, the mid face 4.5 years, and the lower
      face 12.25 years. CONCLUSION: Use of this previously validated self-assessment
      program may prove to be a useful measure of patient-reported improvement with
      treatment.

PMID- 22956882
TI  - Sebusuppressive efficacy of the antioxidant bis-ethylhexyl hydroxydimethoxy
      benzylmalonate in the treatment of oily and blemished skin.
AB  - The aim of this study was to assess the effect of 2% bis-ethylhexyl
      hydroxydimethoxy benzylmalonate (HDBM; RonaCare((r)) AP) as an active ingredient
      in the treatment of oily and blemished skin. This study was carried out as a
      randomized, placebo-controlled, single-blind study on 44 test subjects with
      blemished skin over a period of 8 weeks. Sebum measurement, skin
      inflammation/redness scoring by an expert, photographic documentation and a self
      assessment with regard to skin improvement, and tests of skin compatibility and
      galenic characteristics were performed. Treatment with 2% HDBM resulted in a
      significant reduction of sebum excretion and showed efficacy against inflamed/red
      lesions also shown by photographic documentation. Efficacy and galenic
      performance of 2% HDBM were judged to be superior to the placebo emulsion.
      Additionally, 2% HDBM was well tolerated; approximately 80% of the test subjects
      rated the compatibility as good to very good.

PMID- 22956883
TI  - New developments in the treatment of actinic keratosis: focus on ingenol mebutate
      gel.
AB  - Actinic keratosis is a common disease in older, fair-skinned people, and is a
      consequence of cumulative ultraviolet exposure. It is part of a disease continuum
      in photodamaged skin that may lead to invasive squamous cell carcinoma. Treatment
      options frequently used include cryosurgery and topical pharmacologic agents,
      which are examples of lesion-directed and field-directed strategies. Ingenol
      mebutate gel was recently approved by the US Food and Drug Administration for
      topical treatment of actinic keratosis. While the mechanism of action of ingenol
      mebutate is not fully understood, in vitro and in vivo studies using tumor models
      indicate it has multiple mechanisms. Ingenol mebutate directly induces cell death
      by mitochondrial swelling and loss of cell membrane integrity preferentially in
      transformed keratinocytes. It promotes an inflammatory response characterized by
      infiltration of neutrophils and other immunocompetent cells that kills remaining
      tumor cells. The ability of ingenol mebutate to eliminate mutant p53 patches in
      ultraviolet-irradiated mouse skin suggests that it may have the potential to
      treat chronically ultraviolet-damaged skin. In human studies, ingenol mebutate
      achieved high clearance of actinic keratosis on the head and body after 2-3
      consecutive daily treatments when measured by complete or partial clearance of
      lesions. Localized inflammatory skin responses were generally mild to moderate
      and resolved in less than a month.

PMID- 22956884
TI  - Lenalidomide for the treatment of relapsed and refractory multiple myeloma.
AB  - Lenalidomide is an amino-substituted derivative of thalidomide with direct
      antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as
      antiangiogenic activity and immunomodulatory effects. Together with the
      introduction of bortezomib and thalidomide, lenalidomide has significantly
      improved the survival of patients with relapsed and refractory myeloma. The most
      common adverse events associated with lenalidomide include fatigue, skin rash,
      thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined
      with dexamethasone or other conventional cytotoxic agents, there is an increase
      in the incidence of venous thromboembolic events. There is now evidence that
      continued treatment with lenalidomide has a significant impact on survival by
      improving the depth and duration of response. This highlights the value of
      adverse event management and appropriate dose adjustments to prevent toxicity,
      and of allowing continued treatment until disease progression. In this review, we
      will discuss the different lenalidomide-based treatment regimens for patients
      with relapsed/refractory myeloma. This is accompanied by recommendations of how
      to manage and prevent adverse events associated with lenalidomide-based therapy.

PMID- 22956885
TI  - Prevalence and correlates of dieting in college women: a cross sectional study.
AB  - BACKGROUND: Dieting is a common practice among young women, irrespective of age,
      race, ethnicity, and weight. We aimed to determine the prevalence of dieting and
      its relationship with eating behavior, body weight, and body mass index (BMI) in
      college women. METHODS: This was a cross-sectional survey of female students aged
      18-35 years (n = 308). Measures included BMI, restraint, disinhibition, hunger,
      dieting, weight loss, and perceived weight. RESULTS: A high percentage of college
      females consider themselves overweight or obese, despite having a BMI in the
      normal range. Dieting was practised by 43%, and 32% were avoiding weight gain,
      despite 78% having a healthy BMI. Women classified themselves as overweight or
      obese (27%), while only 11% were actually in these categories. Exercise was a
      common method of weight loss and positive associations were observed between
      dieting and BMI. Assessment of eating behavior showed that 27% were classified as
      high-restraint. Restraint and disinhibition were positively correlated with BMI.
      CONCLUSION: Despite the widespread availability of nutrition information, there
      is incongruity in measured and perceived BMI in young educated women. Dieting
      practices and BMI are associated with restraint and disinhibition. Nutrition
      professionals should consider educating college women about healthy body weight
      regardless of their clients' BMI.

PMID- 22956886
TI  - Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and
      safety.
AB  - Tranexamic acid has proven to be an effective treatment for heavy menstrual
      bleeding (HMB). It reduces menstrual blood loss (MBL) by 26%-60% and is
      significantly more effective than placebo, nonsteroidal anti-inflammatory drugs,
      oral cyclical luteal phase progestins, or oral etamsylate, while the
      levonorgestrel-releasing intrauterine system reduces MBL more than tranexamic
      acid. Other treatments used for HMB are oral contraceptives, danazol, and
      surgical interventions (endometrial ablation and hysterectomy). Medical therapy
      is usually considered a first-line treatment for idiopathic HMB. Tranexamic acid
      significantly improves the quality of life of women treated for HMB. The
      recommended oral dosage is 3.9-4 g/day for 4-5 days starting from the first day
      of the menstrual cycle. Adverse effects are few and mainly mild. No evidence
      exists of an increase in the incidence of thrombotic events associated with its
      use. An active thromboembolic disease is a contraindication. In the US, a history
      of thrombosis or thromboembolism, or an intrinsic risk for thrombosis or
      thromboembolism are considered contraindications as well. This review focuses on
      the efficacy and safety of tranexamic acid in the treatment of idiopathic HMB. We
      searched for medical literature published in English on tranexamic acid from Ovid
      Medline, PubMed, and Cinahl. Additional references were identified from the
      reference lists of articles. Ovid Medline, PubMed, and Cinahl search terms were
      "tranexamic acid" and "menorrhagia" or "heavy menstrual bleeding." Searches were
      last updated on March 25, 2012. Studies with women receiving tranexamic acid for
      HMB were included; randomized controlled studies with a description of
      appropriate statistical methodology were preferred. Relevant data on the
      physiology of menstruation and the pharmacodynamics and pharmacokinetics of
      tranexamic acid are also included.

PMID- 22956887
TI  - A molar masquerading as an ectopic pregnancy in the early first trimester: a
      salutary lesson.
AB  - The authors report a case in which a molar pregnancy was mistaken for an ectopic
      pregnancy in the early first trimester. This confusion delayed diagnosis and
      caused distress; follow-up led to the final diagnosis of complete hydatidiform
      mole. Correct preoperative diagnosis of molar pregnancy by ultrasound in early
      pregnancy may be tricky. It is important to obtain histological evidence to make
      the final diagnosis of gestational trophoblastic disease. While relatively rare,
      consideration of molar pregnancy in the differential diagnosis of early pregnancy
      loss may avoid unnecessary distress.

PMID- 22956888
TI  - Multi-approach model for improving agrochemical safety among rice farmers in
      Pathumthani, Thailand.
AB  - The large-scale use of agrochemicals has raised environmental and human health
      concerns. A comprehensive intervention strategy for improving agrochemical safety
      among rice farmers in Thailand is lacking. The objective of this study is to
      develop a model in order to improve farmers' health and prevent them from being
      exposed to agrochemical hazards, in addition to evaluating the effectiveness of
      the intervention in terms of agrochemical safety. This study was conducted
      between October 2009 and January 2011. It measures changes in the mean scores of
      agrochemical knowledge, health beliefs, agrochemical use behaviors, and in-home
      pesticide safety. Knowledge of agrochemical use constitutes a basic knowledge of
      agrochemicals and agrochemical safety behaviors. Health beliefs constitute
      perceived susceptibility, severity, benefits, and barriers to using
      agrochemicals. Agrochemical use behaviors include self-care practices in terms of
      personal health at specific times including before spraying, while spraying,
      during storage, transportation, waste management, and health risk management.
      Fifty rice farmers from Khlong Seven Community (study group) and 51 rice farmers
      from Bueng Ka Sam community (control group) were randomly recruited with support
      from community leaders. The participants were involved in a combination of home
      visits (ie, pesticide safety assessments at home) and community participatory
      activities regarding agrochemical safety. This study reveals that health risk
      behaviors regarding agrochemical exposure in the study area are mainly caused by
      lack of attention to safety precautions and the use of faulty protective gear.
      After 6 months, the intervention program showed significant improvements in the
      overall scores on knowledge, beliefs, behaviors, and home pesticide safety in the
      study group (P < 0.05). Therefore, this intervention model is effective in
      improving agrochemical safety behaviors among Khlong Seven Community rice
      farmers. These findings demonstrate that a multi-approach model for improving
      agrochemical safety behaviors can lead to sustainable prevention of agrochemical
      hazards for farmers.

PMID- 22956889
TI  - Coverage of genomic medicine: information gap between lay public and scientists.
AB  - The sharing of information between the lay public and medical professionals is
      crucial to the conduct of personalized medicine using genomic information in the
      near future. Mass media, such as newspapers, can play an important role in
      disseminating scientific information. However, studies on the role of newspaper
      coverage of genome-related articles are highly limited. We investigated the
      coverage of genomic medicine in five major Japanese newspapers (Asahi, Mainichi,
      Yomiuri, Sankei, and Nikkei) using Nikkei Telecom and articles in scientific
      journals in PubMed from 1995 to 2009. The number of genome-related articles in
      all five newspapers temporarily increased in 2000, and began continuously
      decreasing thereafter from 2001 to 2009. Conversely, there was a continuous
      increasing trend in the number of genome-related articles in PubMed during this
      period. The numbers of genome-related articles among the five major newspapers
      from 1995 to 2009 were significantly different (P = 0.002). Commentaries,
      research articles, and articles about companies were the most frequent in 2001
      and 2003, when the number of genome-related articles transiently increased in the
      five newspapers. This study highlights the significant gap between newspaper
      coverage and scientific articles in scientific journals.

PMID- 22956890
TI  - Assessing the Sensitivity of Treatment Effect Estimates to Differential Follow-Up
      Rates: Implications for Translational Research.
AB  - We develop a new tool for assessing the sensitivity of findings on treatment
      effectiveness to differential follow-up rates in the two treatment conditions
      being compared. The method censors the group with the higher response rate to
      create a synthetic respondent group that is then compared with the observed cases
      in the other condition to estimate a treatment effect. Censoring is done under
      various assumptions about the strength of the relationship between follow-up and
      outcomes to determine how informative differential dropout can alter inferences
      relative to estimates from models that assume the data are missing at random. The
      method provides an intuitive measure for understanding the strength of the
      association between outcomes and dropout that would be required to alter
      inferences about treatment effects. Our approach is motivated by translational
      research in which treatments found to be effective under experimental conditions
      are tested in standard treatment conditions. In such applications, follow-up
      rates in the experimental setting are likely to be substantially higher than in
      the standard setting, especially when observational data are used in the
      evaluation. We test the method on a case study evaluation of the effectiveness of
      an evidence-supported adolescent substance abuse treatment program (Motivational
      Enhancement Therapy/Cognitive Behavioral Therapy-5 [MET/CBT-5]) delivered by
      community-based treatment providers relative to its performance in a controlled
      research trial. In this case study, follow-up rates in the community based
      settings were extremely low (54%) compared to the experimental setting (95%)
      giving raise to concerns about non-ignorable drop-out.

PMID- 22956891
TI  - Bias and variance trade-offs when combining propensity score weighting and
      regression: with an application to HIV status and homeless men.
AB  - The quality of propensity scores is traditionally measured by assessing how well
      they make the distributions of covariates in the treatment and control groups
      match, which we refer to as "good balance". Good balance guarantees less biased
      estimates of the treatment effect. However, the cost of achieving good balance is
      that the variance of the estimates increases due to a reduction in effective
      sample size, either through the introduction of propensity score weights or
      dropping cases when propensity score matching. In this paper, we investigate
      whether it is best to optimize the balance or to settle for a less than optimal
      balance and use double robust estimation to adjust for remaining differences. We
      compare treatment effect estimates from regression, propensity score weighting,
      and double robust estimation with varying levels of effort expended to achieve
      balance using data from a study about the differences in outcomes by HIV status
      in heterosexually active homeless men residing in Los Angeles. Because of how
      costly data collection efforts are for this population, it is important to find
      an alternative estimation method that does not reduce effective sample size as
      much as methods that aggressively aim to optimize balance. Results from a
      simulation study suggest that there are instances in which we can obtain more
      precise treatment effect estimates without increasing bias too much by using a
      combination of regression and propensity score weights that achieve a less than
      optimal balance. There is a bias-variance tradeoff at work in propensity score
      estimation; every step toward better balance usually means an increase in
      variance and at some point a marginal decrease in bias may not be worth the
      associated increase in variance.

PMID- 22956892
TI  - Empirical bayes model comparisons for differential methylation analysis.
AB  - A number of empirical Bayes models (each with different statistical distribution
      assumptions) have now been developed to analyze differential DNA methylation
      using high-density oligonucleotide tiling arrays. However, it remains unclear
      which model performs best. For example, for analysis of differentially methylated
      regions for conservative and functional sequence characteristics (e.g.,
      enrichment of transcription factor-binding sites (TFBSs)), the sensitivity of
      such analyses, using various empirical Bayes models, remains unclear. In this
      paper, five empirical Bayes models were constructed, based on either a gamma
      distribution or a log-normal distribution, for the identification of differential
      methylated loci and their cell division-(1, 3, and 5) and drug-treatment
      (cisplatin) dependent methylation patterns. While differential methylation
      patterns generated by log-normal models were enriched with numerous TFBSs, we
      observed almost no TFBS-enriched sequences using gamma assumption models.
      Statistical and biological results suggest log-normal, rather than gamma,
      empirical Bayes model distribution to be a highly accurate and precise method for
      differential methylation microarray analysis. In addition, we presented one of
      the log-normal models for differential methylation analysis and tested its
      reproducibility by simulation study. We believe this research to be the first
      extensive comparison of statistical modeling for the analysis of differential DNA
      methylation, an important biological phenomenon that precisely regulates gene
      transcription.

PMID- 22956893
TI  - Differential responses of two broccoli (Brassica oleracea L. var Italica)
      cultivars to salinity and nutritional quality improvement.
AB  - The comparative responses of two broccoli cultivars (Brassica oleracea var.
      Italica, cv. Parthenon and cv. Naxos) to a 15 d exposure to different NaCl levels
      were investigated. Salinity led to increased concentrations of Na(+) and Cl(-)
      ions in both cultivars, a disruption of the endogenous minerals levels in the
      shoots and roots-that varied with the cultivar and salt concentration-and
      decreases in the osmotic potential (Psi(pi)), root hydraulic conductance (L(0)),
      and stomatal conductance (G(s)). The reduced biomass of Naxos at moderate NaCl
      indicates greater sensitivity to salinity, compared with Parthenon. Parthenon
      accumulated more soluble sugars, for osmotic adjustment, whereas Naxos
      accumulated proline, which gave the two cultivars differing nutritional
      characteristics. The total glucosinolates (GSLs) content was not affected by
      salinity in Parthenon while it decreased significantly in Naxos as a consequence
      of the decrease in the indole GSL. However, Naxos accumulated more aliphatic GSLs
      under salt stress than Parthenon, which confers on this cultivar a greater
      nutritional value when cultivated under salinity.These results suggest that, at
      distinct salinity levels, each broccoli cultivar adopts a specific strategy,
      indicating the crucial role of the genetic background on the organoleptic and
      nutritional properties that each cultivar acquires.

PMID- 22956894
TI  - On genetic specificity in symbiont-mediated host-parasite coevolution.
AB  - Existing theory of host-parasite interactions has identified the genetic
      specificity of interaction as a key variable affecting the outcome of
      coevolution. The Matching Alleles (MA) and Gene For Gene (GFG) models have been
      extensively studied as the canonical examples of specific and non-specific
      interaction. The generality of these models has recently been challenged by
      uncovering real-world host-parasite systems exhibiting specificity patterns that
      fit neither MA nor GFG, and by the discovery of symbiotic bacteria protecting
      insect hosts against parasites. In the present paper we address both challenges,
      simulating a large number of non-canonical models of host-parasite interactions
      that explicitly incorporate symbiont-based host resistance. To assess the genetic
      specialisation in these hybrid models, we develop a quantitative index of
      specificity applicable to any coevolutionary model based on a fitness matrix. We
      find qualitative and quantitative effects of host-parasite and symbiont-parasite
      specificities on genotype frequency dynamics, allele survival, and mean host and
      parasite fitnesses.

PMID- 22956895
TI  - Design and implementation of a genomics field trip program aimed at secondary
      school students.
AB  - With the rapid pace of advancements in biological research brought about by the
      application of computer science and information technology, we believe the time
      is right for introducing genomics and bioinformatics tools and concepts to
      secondary school students. Our approach has been to offer a full-day field trip
      in our research facility where secondary school students carry out experiments at
      the laboratory bench and on a laptop computer. This experience offers benefits
      for students, teachers, and field trip instructors. In delivering a wide variety
      of science outreach and education programs, we have learned that a number of
      factors contribute to designing a successful experience for secondary school
      students. First, it is important to engage students with authentic and fun
      activities that are linked to real-world applications and/or research questions.
      Second, connecting with a local high school teacher to pilot programs and linking
      to curricula taught in secondary schools will enrich the field trip experience.
      Whether or not programs are linked directly to local teachers, it is important to
      be flexible and build in mechanisms for collecting feedback in field trip
      programs. Finally, graduate students can be very powerful mentors for students
      and should be encouraged to share their enthusiasm for science and to talk about
      career paths. Our experiences suggest a real need for effective science outreach
      programs at the secondary school level and that genomics and bioinformatics are
      ideal areas to explore.

PMID- 22956896
TI  - Teasing apart translational and transcriptional components of stochastic
      variations in eukaryotic gene expression.
AB  - The intrinsic stochasticity of gene expression leads to cell-to-cell variations,
      noise, in protein abundance. Several processes, including transcription,
      translation, and degradation of mRNA and proteins, can contribute to these
      variations. Recent single cell analyses of gene expression in yeast have
      uncovered a general trend where expression noise scales with protein abundance.
      This trend is consistent with a stochastic model of gene expression where mRNA
      copy number follows the random birth and death process. However, some deviations
      from this basic trend have also been observed, prompting questions about the
      contribution of gene-specific features to such deviations. For example, recent
      studies have pointed to the TATA box as a sequence feature that can influence
      expression noise by facilitating expression bursts. Transcription-originated
      noise can be potentially further amplified in translation. Therefore, we asked
      the question of to what extent sequence features known or postulated to accompany
      translation efficiency can also be associated with increase in noise strength
      and, on average, how such increase compares to the amplification associated with
      the TATA box. Untangling different components of expression noise is highly
      nontrivial, as they may be gene or gene-module specific. In particular, focusing
      on codon usage as one of the sequence features associated with efficient
      translation, we found that ribosomal genes display a different relationship
      between expression noise and codon usage as compared to other genes. Within
      nonribosomal genes we found that sequence high codon usage is correlated with
      increased noise relative to the average noise of proteins with the same
      abundance. Interestingly, by projecting the data on a theoretical model of gene
      expression, we found that the amplification of noise strength associated with
      codon usage is comparable to that of the TATA box, suggesting that the effect of
      translation on noise in eukaryotic gene expression might be more prominent than
      previously appreciated.

PMID- 22956897
TI  - Mutual repression enhances the steepness and precision of gene expression
      boundaries.
AB  - Embryonic development is driven by spatial patterns of gene expression that
      determine the fate of each cell in the embryo. While gene expression is often
      highly erratic, embryonic development is usually exceedingly precise. In
      particular, gene expression boundaries are robust not only against intra
      embryonic fluctuations such as noise in gene expression and protein diffusion,
      but also against embryo-to-embryo variations in the morphogen gradients, which
      provide positional information to the differentiating cells. How development is
      robust against intra- and inter-embryonic variations is not understood. A common
      motif in the gene regulation networks that control embryonic development is
      mutual repression between pairs of genes. To assess the role of mutual repression
      in the robust formation of gene expression patterns, we have performed large
      scale stochastic simulations of a minimal model of two mutually repressing gap
      genes in Drosophila, hunchback (hb) and knirps (kni). Our model includes not only
      mutual repression between hb and kni, but also the stochastic and cooperative
      activation of hb by the anterior morphogen Bicoid (Bcd) and of kni by the
      posterior morphogen Caudal (Cad), as well as the diffusion of Hb and Kni between
      neighboring nuclei. Our analysis reveals that mutual repression can markedly
      increase the steepness and precision of the gap gene expression boundaries. In
      contrast to other mechanisms such as spatial averaging and cooperative gene
      activation, mutual repression thus allows for gene-expression boundaries that are
      both steep and precise. Moreover, mutual repression dramatically enhances their
      robustness against embryo-to-embryo variations in the morphogen levels. Finally,
      our simulations reveal that diffusion of the gap proteins plays a critical role
      not only in reducing the width of the gap gene expression boundaries via the
      mechanism of spatial averaging, but also in repairing patterning errors that
      could arise because of the bistability induced by mutual repression.

PMID- 22956898
TI  - Weighted frequent gene co-expression network mining to identify genes involved in
      genome stability.
AB  - Gene co-expression network analysis is an effective method for predicting gene
      functions and disease biomarkers. However, few studies have systematically
      identified co-expressed genes involved in the molecular origin and development of
      various types of tumors. In this study, we used a network mining algorithm to
      identify tightly connected gene co-expression networks that are frequently
      present in microarray datasets from 33 types of cancer which were derived from 16
      organs/tissues. We compared the results with networks found in multiple normal
      tissue types and discovered 18 tightly connected frequent networks in cancers,
      with highly enriched functions on cancer-related activities. Most networks
      identified also formed physically interacting networks. In contrast, only 6
      networks were found in normal tissues, which were highly enriched for
      housekeeping functions. The largest cancer network contained many genes with
      genome stability maintenance functions. We tested 13 selected genes from this
      network for their involvement in genome maintenance using two cell-based assays.
      Among them, 10 were shown to be involved in either homology-directed DNA repair
      or centrosome duplication control including the well-known cancer marker MKI67.
      Our results suggest that the commonly recognized characteristics of cancers are
      supported by highly coordinated transcriptomic activities. This study also
      demonstrated that the co-expression network directed approach provides a powerful
      tool for understanding cancer physiology, predicting new gene functions, as well
      as providing new target candidates for cancer therapeutics.

PMID- 22956899
TI  - Shrinking the metabolic solution space using experimental datasets.
AB  - Constraint-based models of metabolism have been used in a variety of studies on
      drug discovery, metabolic engineering, evolution, and multi-species interactions.
      These genome-scale models can be generated for any sequenced organism since their
      main parameters (i.e., reaction stoichiometry) are highly conserved. Their
      relatively low parameter requirement makes these models easy to develop; however,
      these models often result in a solution space with multiple possible flux
      distributions, making it difficult to determine the precise flux state in the
      cell. Recent research efforts in this modeling field have investigated how
      additional experimental data, including gene expression, protein expression,
      metabolite concentrations, and kinetic parameters, can be used to reduce the
      solution space. This mini-review provides a summary of the data-driven
      computational approaches that are available for reducing the solution space and
      thereby improve predictions of intracellular fluxes by constraint-based models.

PMID- 22956900
TI  - Quantitative predictions of binding free energy changes in drug-resistant
      influenza neuraminidase.
AB  - Quantitatively predicting changes in drug sensitivity associated with residue
      mutations is a major challenge in structural biology. By expanding the limits of
      free energy calculations, we successfully identified mutations in influenza
      neuraminidase (NA) that confer drug resistance to two antiviral drugs, zanamivir
      and oseltamivir. We augmented molecular dynamics (MD) with Hamiltonian Replica
      Exchange and calculated binding free energy changes for H274Y, N294S, and Y252H
      mutants. Based on experimental data, our calculations achieved high accuracy and
      precision compared with results from established computational methods. Analysis
      of 15 micros of aggregated MD trajectories provided insights into the molecular
      mechanisms underlying drug resistance that are at odds with current
      interpretations of the crystallographic data. Contrary to the notion that
      resistance is caused by mutant-induced changes in hydrophobicity of the binding
      pocket, our simulations showed that drug resistance mutations in NA led to subtle
      rearrangements in the protein structure and its dynamics that together alter the
      active-site electrostatic environment and modulate inhibitor binding.
      Importantly, different mutations confer resistance through different
      conformational changes, suggesting that a generalized mechanism for NA drug
      resistance is unlikely.

PMID- 22956901
TI  - External drive to inhibitory cells induces alternating episodes of high- and low
      amplitude oscillations.
AB  - Electrical oscillations in neuronal network activity are ubiquitous in the brain
      and have been associated with cognition and behavior. Intriguingly, the amplitude
      of ongoing oscillations, such as measured in EEG recordings, fluctuates
      irregularly, with episodes of high amplitude alternating with episodes of low
      amplitude. Despite the widespread occurrence of amplitude fluctuations in many
      frequency bands and brain regions, the mechanisms by which they are generated are
      poorly understood. Here, we show that irregular transitions between sub-second
      episodes of high- and low-amplitude oscillations in the alpha/beta frequency band
      occur in a generic neuronal network model consisting of interconnected inhibitory
      and excitatory cells that are externally driven by sustained cholinergic input
      and trains of action potentials that activate excitatory synapses. In the model,
      we identify the action potential drive onto inhibitory cells, which represents
      input from other brain areas and is shown to desynchronize network activity, to
      be crucial for the emergence of amplitude fluctuations. We show that the duration
      distributions of high-amplitude episodes in the model match those observed in rat
      prefrontal cortex for oscillations induced by the cholinergic agonist carbachol.
      Furthermore, the mean duration of high-amplitude episodes varies in a bell-shaped
      manner with carbachol concentration, just as in mouse hippocampus. Our results
      suggest that amplitude fluctuations are a general property of oscillatory
      neuronal networks that can arise through background input from areas external to
      the network.

PMID- 22956902
TI  - Sub-diffraction limit localization of proteins in volumetric space using Bayesian
      restoration of fluorescence images from ultrathin specimens.
AB  - Photon diffraction limits the resolution of conventional light microscopy at the
      lateral focal plane to 0.61lambda/NA (lambda = wavelength of light, NA =
      numerical aperture of the objective) and at the axial plane to 1.4nlambda/NA(2)
      (n = refractive index of the imaging medium, 1.51 for oil immersion), which with
      visible wavelengths and a 1.4NA oil immersion objective is -220 nm and -600 nm in
      the lateral plane and axial plane respectively. This volumetric resolution is too
      large for the proper localization of protein clustering in subcellular
      structures. Here we combine the newly developed proteomic imaging technique,
      Array Tomography (AT), with its native 50-100 nm axial resolution achieved by
      physical sectioning of resin embedded tissue, and a 2D maximum likelihood
      deconvolution method, based on Bayes' rule, which significantly improves the
      resolution of protein puncta in the lateral plane to allow accurate and fast
      computational segmentation and analysis of labeled proteins. The physical
      sectioning of AT allows tissue specimens to be imaged at the physical optimum of
      modern high NA plan-apochormatic objectives. This translates to images that have
      little out of focus light, minimal aberrations and wave-front distortions. Thus,
      AT is able to provide images with truly invariant point spread functions (PSF), a
      property critical for accurate deconvolution. We show that AT with deconvolution
      increases the volumetric analytical fidelity of protein localization by
      significantly improving the modulation of high spatial frequencies up to and
      potentially beyond the spatial frequency cut-off of the objective. Moreover, we
      are able to achieve this improvement with no noticeable introduction of noise or
      artifacts and arrive at object segmentation and localization accuracies on par
      with image volumes captured using commercial implementations of super-resolution
      microscopes.

PMID- 22956903
TI  - Interplay of gene expression noise and ultrasensitive dynamics affects bacterial
      operon organization.
AB  - Bacterial chromosomes are organized into polycistronic cotranscribed operons, but
      the evolutionary pressures maintaining them are unclear. We hypothesized that
      operons alter gene expression noise characteristics, resulting in selection for
      or against maintaining operons depending on network architecture. Mathematical
      models for 6 functional classes of network modules showed that three classes
      exhibited decreased noise and 3 exhibited increased noise with same-operon
      cotranscription of interacting proteins. Noise reduction was often associated
      with a decreased chance of reaching an ultrasensitive threshold. Stochastic
      simulations of the lac operon demonstrated that the predicted effects of
      transcriptional coupling hold for a complex network module. We employed
      bioinformatic analysis to find overrepresentation of noise-minimizing operon
      organization compared with randomized controls. Among constitutively expressed
      physically interacting protein pairs, higher coupling frequencies appeared at
      lower expression levels, where noise effects are expected to be dominant. Our
      results thereby suggest an important role for gene expression noise, in many
      cases interacting with an ultrasensitive switch, in maintaining or selecting for
      operons in bacterial chromosomes.

PMID- 22956904
TI  - Molecular dynamics simulations reveal proton transfer pathways in cytochrome C
      dependent nitric oxide reductase.
AB  - Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction
      of nitric oxide (NO) to nitrous oxide (N(2)O), which is a critical step of the
      nitrate respiration process in denitrifying bacteria. Using the recently
      determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino
      T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis
      of biological N2O generation by bacterial nitric oxide reductase. Science 330:
      1666-70.], we performed extensive all-atom molecular dynamics (MD) simulations of
      cNOR within an explicit membrane/solvent environment to fully characterize water
      distribution and dynamics as well as hydrogen-bonded networks inside the protein,
      yielding the atomic details of functionally important proton channels.
      Simulations reveal two possible proton transfer pathways leading from the
      periplasm to the active site, while no pathways from the cytoplasmic side were
      found, consistently with the experimental observations that cNOR is not a proton
      pump. One of the pathways, which was newly identified in the MD simulation, is
      blocked in the crystal structure and requires small structural rearrangements to
      allow for water channel formation. That pathway is equivalent to the functional
      periplasmic cavity postulated in cbb(3) oxidase, which illustrates that the two
      enzymes share some elements of the proton transfer mechanisms and confirms a
      close evolutionary relation between NORs and C-type oxidases. Several mechanisms
      of the critical proton transfer steps near the catalytic center are proposed.

PMID- 22956905
TI  - Nonhuman primate models for HIV cure research.

PMID- 22956906
TI  - CPSF6 defines a conserved capsid interface that modulates HIV-1 replication.
AB  - The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein.
      Variation in CA sequence alters HIV-1 infectivity and escape from host
      restriction factors. However, apart from the Cyclophilin A-binding loop, CA has
      no known interfaces with which to interact with cellular cofactors. Here we
      describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA,
      determined by X-ray crystallography, which mediates both viral restriction and
      host cofactor dependence. The interface is highly conserved across lentiviruses
      and is accessible in the context of a hexameric lattice. Mutation of the
      interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic
      form of the RNA processing factor, cleavage and polyadenylation specific factor 6
      (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve
      dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest
      that the HIV-1 capsid mediates direct host cofactor interactions to facilitate
      viral infection.

PMID- 22956907
TI  - Establishment of a reverse genetics system for studying human bocavirus in human
      airway epithelia.
AB  - Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of
      wheezing in young children with acute respiratory-tract infections. In this
      study, we have obtained the sequence of a full-length HBoV1 genome (including
      both termini) using viral DNA extracted from a nasopharyngeal aspirate of an
      infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA
      replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions
      from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell
      line-based production system exhibits a typical icosahedral structure of
      approximately 26 nm in diameter, and is capable of productively infecting
      polarized primary human airway epithelia (HAE) from the apical surface. Infected
      HAE showed hallmarks of lung airway-tract injury, including disruption of the
      tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably,
      polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8
      (originally derived from a cystic fibrosis patient), also supported productive
      infection of HBoV1. Thus, we have established a reverse genetics system and
      generated the first cell line-based culture system for the study of HBoV1
      infection, which will significantly advance the study of HBoV1 replication and
      pathogenesis.

PMID- 22956908
TI  - Condensin II promotes the formation of chromosome territories by inducing axial
      compaction of polyploid interphase chromosomes.
AB  - The eukaryotic nucleus is both spatially and functionally partitioned. This
      organization contributes to the maintenance, expression, and transmission of
      genetic information. Though our ability to probe the physical structure of the
      genome within the nucleus has improved substantially in recent years, relatively
      little is known about the factors that regulate its organization or the
      mechanisms through which specific organizational states are achieved. Here, we
      show that Drosophila melanogaster Condensin II induces axial compaction of
      interphase chromosomes, globally disrupts interchromosomal interactions, and
      promotes the dispersal of peri-centric heterochromatin. These Condensin II
      activities compartmentalize the nucleus into discrete chromosome territories and
      indicate commonalities in the mechanisms that regulate the spatial structure of
      the genome during mitosis and interphase.

PMID- 22956909
TI  - Dynamic distribution of linker histone H1.5 in cellular differentiation.
AB  - Linker histones are essential components of chromatin, but the distributions and
      functions of many during cellular differentiation are not well understood. Here,
      we show that H1.5 binds to genic and intergenic regions, forming blocks of
      enrichment, in differentiated human cells from all three embryonic germ layers
      but not in embryonic stem cells. In differentiated cells, H1.5, but not H1.3,
      binds preferentially to genes that encode membrane and membrane-related proteins.
      Strikingly, 37% of H1.5 target genes belong to gene family clusters, groups of
      homologous genes that are located in proximity to each other on chromosomes. H1.5
      binding is associated with gene repression and is required for SIRT1 binding,
      H3K9me2 enrichment, and chromatin compaction. Depletion of H1.5 results in loss
      of SIRT1 and H3K9me2, increased chromatin accessibility, deregulation of gene
      expression, and decreased cell growth. Our data reveal for the first time a
      specific and novel function for linker histone subtype H1.5 in maintenance of
      condensed chromatin at defined gene families in differentiated human cells.

PMID- 22956910
TI  - Genome patterns of selection and introgression of haplotypes in natural
      populations of the house mouse (Mus musculus).
AB  - General parameters of selection, such as the frequency and strength of positive
      selection in natural populations or the role of introgression, are still
      insufficiently understood. The house mouse (Mus musculus) is a particularly well
      suited model system to approach such questions, since it has a defined history of
      splits into subspecies and populations and since extensive genome information is
      available. We have used high-density single-nucleotide polymorphism (SNP) typing
      arrays to assess genomic patterns of positive selection and introgression of
      alleles in two natural populations of each of the subspecies M. m. domesticus and
      M. m. musculus. Applying different statistical procedures, we find a large number
      of regions subject to apparent selective sweeps, indicating frequent positive
      selection on rare alleles or novel mutations. Genes in the regions include well
      studied imprinted loci (e.g. Plagl1/Zac1), homologues of human genes involved in
      adaptations (e.g. alpha-amylase genes) or in genetic diseases (e.g. Huntingtin
      and Parkin). Haplotype matching between the two subspecies reveals a large number
      of haplotypes that show patterns of introgression from specific populations of
      the respective other subspecies, with at least 10% of the genome being affected
      by partial or full introgression. Using neutral simulations for comparison, we
      find that the size and the fraction of introgressed haplotypes are not compatible
      with a pure migration or incomplete lineage sorting model. Hence, it appears that
      introgressed haplotypes can rise in frequency due to positive selection and thus
      can contribute to the adaptive genomic landscape of natural populations. Our data
      support the notion that natural genomes are subject to complex adaptive
      processes, including the introgression of haplotypes from other differentiated
      populations or species at a larger scale than previously assumed for animals.
      This implies that some of the admixture found in inbred strains of mice may also
      have a natural origin.

PMID- 22956911
TI  - The PARN deadenylase targets a discrete set of mRNAs for decay and regulates cell
      motility in mouse myoblasts.
AB  - PARN is one of several deadenylase enzymes present in mammalian cells, and as
      such the contribution it makes to the regulation of gene expression is unclear.
      To address this, we performed global mRNA expression and half-life analysis on
      mouse myoblasts depleted of PARN. PARN knockdown resulted in the stabilization of
      40 mRNAs, including that encoding the mRNA decay factor ZFP36L2. Additional
      experiments demonstrated that PARN knockdown induced an increase in Zfp36l2
      poly(A) tail length as well as increased translation. The elements responsible
      for PARN-dependent regulation lie within the 3' UTR of the mRNA. Surprisingly,
      changes in mRNA stability showed an inverse correlation with mRNA abundance;
      stabilized transcripts showed either no change or a decrease in mRNA abundance.
      Moreover, we found that stabilized mRNAs had reduced accumulation of pre-mRNA,
      consistent with lower transcription rates. This presents compelling evidence for
      the coupling of mRNA decay and transcription to buffer mRNA abundances. Although
      PARN knockdown altered decay of relatively few mRNAs, there was a much larger
      effect on global gene expression. Many of the mRNAs whose abundance was reduced
      by PARN knockdown encode factors required for cell migration and adhesion. The
      biological relevance of this observation was demonstrated by the fact that PARN
      KD cells migrate faster in wound-healing assays. Collectively, these data
      indicate that PARN modulates decay of a defined set of mRNAs in mammalian cells
      and implicate this deadenylase in coordinating control of genes required for cell
      movement.

PMID- 22956912
TI  - A sexual ornament in chickens is affected by pleiotropic alleles at HAO1 and
      BMP2, selected during domestication.
AB  - Domestication is one of the strongest forms of short-term, directional selection.
      Although selection is typically only exerted on one or a few target traits,
      domestication can lead to numerous changes in many seemingly unrelated
      phenotypes. It is unknown whether such correlated responses are due to pleiotropy
      or linkage between separate genetic architectures. Using three separate
      intercrosses between wild and domestic chickens, a locus affecting comb mass (a
      sexual ornament in the chicken) and several fitness traits (primarily medullary
      bone allocation and fecundity) was identified. This locus contains two tightly
      linked genes, BMP2 and HAO1, which together produce the range of pleiotropic
      effects seen. This study demonstrates the importance of pleiotropy (or extremely
      close linkage) in domestication. The nature of this pleiotropy also provides
      insights into how this sexual ornament could be maintained in wild populations.

PMID- 22956913
TI  - Role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes.
AB  - Nuclear export of mRNAs and pre-ribosomal subunits (pre40S and pre60S) is
      fundamental to all eukaryotes. While genetic approaches in budding yeast have
      identified bona fide export factors for mRNAs and pre60S subunits, little is
      known regarding nuclear export of pre40S subunits. The yeast heterodimeric
      transport receptor Mex67-Mtr2 (TAP-p15 in humans) binds mRNAs and pre60S subunits
      in the nucleus and facilitates their passage through the nuclear pore complex
      (NPC) into the cytoplasm by interacting with Phe-Gly (FG)-rich nucleoporins that
      line its transport channel. By exploiting a combination of genetic, cell
      biological, and biochemical approaches, we uncovered an unanticipated role of
      Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. We show that recruitment
      of Mex67-Mtr2 to pre40S subunits requires loops emanating from its NTF2-like
      domains and that the C-terminal FG-rich nucleoporin interacting UBA-like domain
      within Mex67 contributes to the transport of pre40S subunits to the cytoplasm.
      Remarkably, the same loops also recruit Mex67-Mtr2 to pre60S subunits and to the
      Nup84 complex, the respective interactions crucial for nuclear export of pre60S
      subunits and mRNAs. Thus Mex67-Mtr2 is a unique transport receptor that employs a
      common interaction surface to participate in the nuclear export of both pre
      ribosomal subunits and mRNAs. Mex67-Mtr2 could engage a regulatory crosstalk
      among the three major export pathways for optimal cellular growth and
      proliferation.

PMID- 22956914
TI  - Experimental evolution of a novel sexually antagonistic allele.
AB  - Evolutionary conflict permeates biological systems. In sexually reproducing
      organisms, sex-specific optima mean that the same allele can have sexually
      antagonistic expression, i.e. beneficial in one sex and detrimental in the other,
      a phenomenon known as intralocus sexual conflict. Intralocus sexual conflict is
      emerging as a potentially fundamental factor for the genetic architecture of
      fitness, with important consequences for evolutionary processes. However, no
      study to date has directly experimentally tested the evolutionary fate of a
      sexually antagonistic allele. Using genetic constructs to manipulate female
      fecundity and male mating success, we engineered a novel sexually antagonistic
      allele (SAA) in Drosophila melanogaster. The SAA is nearly twice as costly to
      females as it is beneficial to males, but the harmful effects to females are
      recessive and X-linked, and thus are rarely expressed when SAA occurs at low
      frequency. We experimentally show how the evolutionary dynamics of the novel SAA
      are qualitatively consistent with the predictions of population genetic models:
      SAA frequency decreases when common, but increases when rare, converging toward
      an equilibrium frequency of ~8%. Furthermore, we show that persistence of the SAA
      requires the mating advantage it provides to males: the SAA frequency declines
      towards extinction when the male advantage is experimentally abolished. Our
      results empirically demonstrate the dynamics underlying the evolutionary fate of
      a sexually antagonistic allele, validating a central assumption of intralocus
      sexual conflict theory: that variation in fitness-related traits within
      populations can be maintained via sex-linked sexually antagonistic loci.

PMID- 22956915
TI  - ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum
      of old ataxic knock-in mice.
AB  - Spinocerebellar Ataxia Type 2 (SCA2) is caused by expansion of a polyglutamine
      encoding triplet repeat in the human ATXN2 gene beyond (CAG)(31). This is thought
      to mediate toxic gain-of-function by protein aggregation and to affect RNA
      processing, resulting in degenerative processes affecting preferentially
      cerebellar neurons. As a faithful animal model, we generated a knock-in mouse
      replacing the single CAG of murine Atxn2 with CAG42, a frequent patient genotype.
      This expansion size was inherited stably. The mice showed phenotypes with reduced
      weight and later motor incoordination. Although brain Atxn2 mRNA became elevated,
      soluble ATXN2 protein levels diminished over time, which might explain partial
      loss-of-function effects. Deficits in soluble ATXN2 protein correlated with the
      appearance of insoluble ATXN2, a progressive feature in cerebellum possibly
      reflecting toxic gains-of-function. Since in vitro ATXN2 overexpression was known
      to reduce levels of its protein interactor PABPC1, we studied expansion effects
      on PABPC1. In cortex, PABPC1 transcript and soluble and insoluble protein levels
      were increased. In the more vulnerable cerebellum, the progressive insolubility
      of PABPC1 was accompanied by decreased soluble protein levels, with PABPC1 mRNA
      showing no compensatory increase. The sequestration of PABPC1 into insolubility
      by ATXN2 function gains was validated in human cell culture. To understand
      consequences on mRNA processing, transcriptome profiles at medium and old age in
      three different tissues were studied and demonstrated a selective induction of
      Fbxw8 in the old cerebellum. Fbxw8 is encoded next to the Atxn2 locus and was
      shown in vitro to decrease the level of expanded insoluble ATXN2 protein. In
      conclusion, our data support the concept that expanded ATXN2 undergoes
      progressive insolubility and affects PABPC1 by a toxic gain-of-function mechanism
      with tissue-specific effects, which may be partially alleviated by the induction
      of FBXW8.

PMID- 22956917
TI  - Chromosome territories meet a condensin.

PMID- 22956916
TI  - Drosophila melanogaster Acetyl-CoA-carboxylase sustains a fatty acid-dependent
      remote signal to waterproof the respiratory system.
AB  - Fatty acid (FA) metabolism plays a central role in body homeostasis and related
      diseases. Thus, FA metabolic enzymes are attractive targets for drug therapy.
      Mouse studies on Acetyl-coenzymeA-carboxylase (ACC), the rate-limiting enzyme for
      FA synthesis, have highlighted its homeostatic role in liver and adipose tissue.
      We took advantage of the powerful genetics of Drosophila melanogaster to
      investigate the role of the unique Drosophila ACC homologue in the fat body and
      the oenocytes. The fat body accomplishes hepatic and storage functions, whereas
      the oenocytes are proposed to produce the cuticular lipids and to contribute to
      the hepatic function. RNA-interfering disruption of ACC in the fat body does not
      affect viability but does result in a dramatic reduction in triglyceride storage
      and a concurrent increase in glycogen accumulation. These metabolic perturbations
      further highlight the role of triglyceride and glycogen storage in controlling
      circulatory sugar levels, thereby validating Drosophila as a relevant model to
      explore the tissue-specific function of FA metabolic enzymes. In contrast, ACC
      disruption in the oenocytes through RNA-interference or tissue-targeted mutation
      induces lethality, as does oenocyte ablation. Surprisingly, this lethality is
      associated with a failure in the watertightness of the spiracles-the organs
      controlling the entry of air into the trachea. At the cellular level, we have
      observed that, in defective spiracles, lipids fail to transfer from the
      spiracular gland to the point of air entry. This phenotype is caused by disrupted
      synthesis of a putative very-long-chain-FA (VLCFA) within the oenocytes, which
      ultimately results in a lethal anoxic issue. Preventing liquid entry into
      respiratory systems is a universal issue for air-breathing animals. Here, we have
      shown that, in Drosophila, this process is controlled by a putative VLCFA
      produced within the oenocytes.

PMID- 22956918
TI  - The Longibrachiatum Clade of Trichoderma: a revision with new species.
AB  - The Longibrachiatum Clade of Trichoderma is revised. Eight new species are
      described (T. aethiopicum, T. capillare, T. flagellatum, T. gillesii, T. gracile,
      T. pinnatum, T. saturnisporopsis, T. solani). The twenty-one species known to
      belong to the Longibrachiatum Clade are included in a synoptic key. Trichoderma
      parareesei and T. effusum are redescribed based on new collections or additional
      observations. Hypocrea teleomorphs are reported for T. gillesii and T. pinnatum.
      Previously described species are annotated.

PMID- 22956919
TI  - Synthesis Characterization and DNA Interaction Studies of a New Zn(II) Complex
      Containing Different Dinitrogen Aromatic Ligands.
AB  - A mononuclear complex of Zn(II), [Zn(DIP)(2) (DMP)] (NO(3))(2).2H(2)O in which
      DIP is 4,7-diphenyl-1,10-phenanthroline and DMP is 4,4'-dimethyl-2,2'-bipyridine
      has been prepared and characterized by (1)HNMR spectroscopy, FT-IR, UV-Vis and
      elemental analysis techniques. DNA-binding properties of the complex were studied
      using UV-vis spectra, circular dichroism (CD) spectra, fluorescence, cyclic
      voltammetry (CV), and viscosity measurements. The results indicate that this
      zinc(II) complex can intercalate into the stacked base pairs of DNA and compete
      with the strong intercalator ethidium bromide for the intercalative binding
      sites.

PMID- 22956920
TI  - Metals in medicine.

PMID- 22956921
TI  - The 'burden of evidence'.

PMID- 22956922
TI  - The random allocation process: two things you need to know.

PMID- 22956923
TI  - Outcome of major spinal deformity surgery in high-risk patients: comparison
      between two departments.
AB  - STUDY DESIGN:  Retrospective cohort studyObjective: To describe the outcome and
      resource use in major spine surgery on high-risk patients, and analyze possible
      differences between two surgical departments. METHODS:  Data from the deformity
      register and medical records of 136 patients, median age 12-years, with
      neuromuscular and congenital spinal deformities with and without intraspinal
      pathology, surgically treated by one surgeon from 1997 through 2004 at two
      departments. H1 with a pediatric multidisciplinary team, and H2 with focus on
      adult spine. Variables at baseline: age, gender, diagnosis, curve size, and type
      of surgical procedure. Result variables included clinical and radiographic
      outcome, surgery time, length of intensive care and hospital stay, relative blood
      loss, and occurrence of complications during 2 or more years follow-up. RESULTS: 
      There was no perioperative or postoperative mortality, no spinal-cord damage, no
      neurological or ambulatory function deterioration. The overall complication rate
      was 36%, and the overall major complication rate was 15.4%. The mean loss of
      correction was 2 degrees  during the follow-up. There were statistically
      significant differences between the H1 and H2 departments. At H1, deformity
      correction was better and surgery time shorter. Infections were more frequent at
      H2 (P = .04; 6/65 at H1; 16/71 at H2), tendency (P = .06) of more department
      related complications was higher at H2. CONCLUSIONS:  Major spine surgery in high
      risk patients can be performed safely and with good outcoms. Impact of
      organization and workplace culture on the outcome might be important and worth
      further study.

PMID- 22956924
TI  - Reliability of classification systems for subaxial cervical injuries.
AB  - STUDY DESIGN:  Interobserver and intraobserver reliabilityObjective: To measure
      and compare the interobserver and intraobserver reliability of the cervical spine
      injury severity score (CSISS), the subaxial injury classification (SLIC) and
      severity scale, and the Allen-Ferguson system in patients with subaxial cervical
      spine injuries presenting to the emergency department. METHODS:  Five examiners
      independently reviewed c-spine x-rays (CT/MRI) of 50 consecutive patients with
      subaxial cervical-spine injuries. They classified each case using CSISS, SLIC,
      and the Allen-Ferguson system. Examiners also documented if they believed the
      case required surgical management. At least 6 weeks later, the above steps were
      repeated for ten randomly chosen cases. RESULTS:  The interobserver and
      intraobserver reliability for the total CSISS and total SLIC score are excellent.
      There is poor interobserver reliability and excellent intraobserver reliability
      when a total kappa score is calculated using all 21 groups for the Allen-Ferguson
      system. With respect to surgical management decisions, the interobserver
      agreement is moderate and the intraobserver agreement is excellent. CONCLUSIONS: 
      There is no universally accepted classification scheme for subaxial cervical
      spine injuries. A useful classification system must have excellent reliability to
      consistently and accurately describe injury patterns between different observers
      and allow for comparison across systems or cohorts. Both the CSISS and the SLIC
      and severity scale are promising classification systems with excellent
      interobserver and intraobserver reliability. Future studies will need to
      determine if their quantitative scores correlate with management and clinical
      outcomes.

PMID- 22956925
TI  - Open door expansive laminoplasty and postoperative axial symptoms: a comparative
      study between two different procedures.
AB  - STUDY DESIGN:  Retrospective cohortObjective: To determine if there are
      differences in important clinical outcomes between patients treated with a
      "preservation of the unilateral posterior muscular-ligament complex (PMLC)
      procedure" and a "hinge side anchoring procedure (HSAP)" for the treatment of
      cervical spondylotic myelopathy (CSM). METHODS:  Nine hundred and forty-six
      patients underwent the above procedures for treatment of CSM between January 2006
      and December 2009. Five hundred and fifty-two (58%) subjects met study criteria
      and 136 were analyzed (76% unavailable for follow-up). One group (70 patients)
      received a "preservation of unilateral PMLC procedure" and another group (66
      patients) received an HSAP. The rate and severity of postoperative axial symptoms
      were assessed, and the changes of cervical-spine curvature and postoperative
      decompression were measured. RESULTS:  The mean time to follow-up in the
      preservation of unilateral PMLC group was 6.9 months (range, 6-8 months) and the
      HSAP group was 6.4 months (6-8 months). The overall rate of any axial symptoms
      (AS) among all subjects was 35%. No AS was reported in 45.7% of the preservation
      of unilateral PMLC group and 23.8% of the HSAP group (P = .008). Severe AS was
      reported in 4.3% and 11.1% of patients per group, respectively (P = .14).
      Cervical spinal lordosis was improved in the unilateral PMLC group and decreased
      in the HSAP group. The risk of losing lordosis was more than two times higher in
      the HSAP group compared with the unilateral PMLC group (70% and 34%,
      respectively; P < .001). CONCLUSION:  Differences were observed between the two
      groups; however, a high loss to follow-up rate weakens the findings. Cervical
      expansive laminoplasty with preservation of unilateral PMLC may have the
      advantage of a lower rate of postoperative AS and maintenance of cervical spinal
      lordosis compared with the HSAP group.

PMID- 22956926
TI  - Chronic sacroiliac joint pain: fusion versus denervation as treatment options.
AB  - STUDY DESIGN:  Systematic reviewObjective: To compare the safety and
      effectiveness of fusion versus denervation for chronic sacroiliac joint pain
      after failed conservative management. SUMMARY OF BACKGROUND:  METHODS of
      confirming the sacroiliac joint as a pain source have been extensively studied
      and reported in the literature. After confirmation of the origin of the pain by
      positive local anesthetic blocks, chronic sacroiliac joint pain is usually
      managed with a combination of medication, physical therapies, and injections. We
      have chosen to compare two alternative treatments for sacroiliac pain that was
      refractory to conservative therapies. METHODS:  A systematic review of the
      English-language literature was undertaken for articles published between 1970
      and June 2010. Electronic databases and reference lists of key articles were
      searched to identify studies evaluating fusion or denervation for chronic
      sacroiliac joint pain after failed conservative management. Studies involving
      only conservative treatment or traumatic onset of injury were excluded. Two
      independent reviewers assessed the level of evidence quality using the grading of
      recommendations assessment, development and evaluation (GRADE) system, and
      disagreements were resolved by consensus. RESULTS:  We identified eleven articles
      (six fusion, five denervation) meeting our inclusion criteria. The majority of
      patients report satisfaction after both treatments. Both treatments reported mean
      improvements in pain and functional outcome. Rates of complications were higher
      among fusion studies (13.7%) compared to denervation studies (7.3%). Only fusion
      studies reported infections (5.3%). No infections were reported among denervation
      patients. The evidence for all findings were very low to low; therefore, the
      relative efficacy or safety of one treatment over another cannot be established.
      CONCLUSIONS:  Sacroiliac joint fusion or denervation can reduce pain for many
      patients. Whether a true arthrodesis of the joint is achieved by percutaneous
      techniques is open to question and whether denervation of the joint gives durable
      pain relief is not clear. Further comparative studies of these two techniques may
      provide the answers.

PMID- 22956927
TI  - Anterior cervical discectomy and fusion for the management of axial neck pain in
      the absence of radiculopathy or myelopathy.
AB  - STUDY DESIGN:  Systematic reviewStudy rationale: Anterior cervical discectomy and
      fusion (ACDF) is a proven, effective treatment for relieving neck pain due to
      degenerative conditions of the cervical spine. Since most patients also present
      with radiculopathy or myelopathy, little is known as to the effectiveness of ACDF
      to relieve pain and improve function in patients without radicular or myelopathic
      symptoms. OBJECTIVE:  To examine the clinical outcome in patients undergoing
      (ACDF) for axial neck pain without radicular or myelopathic symptoms. METHODS:  A
      systematic review was undertaken for articles published up to March 2010.
      Electronic databases and reference lists of key articles were searched to
      identify studies evaluating ACDF for the treatment of axial neck pain only.
      Radiculopathy and myelopathy, patients who suffered severe trauma, or with
      tumor/metastatic disease or infection were excluded. Two independent reviewers
      assessed the strength of evidence using the grading of recommendations
      assessment, development and evaluation (GRADE) system, and disagreements were
      resolved by consensus. RESULTS:  No comparative studies were identified. Three
      case series met our inclusion criteria and were evaluated. All studies showed a
      mean improvement of pain of at least 50% approximately 4-years following surgery.
      Functional outcomes improved between 32% and 52% from baseline. Most patients
      reported satisfaction with surgery, 56% in one study and 79% in another.
      Complications varied among studies ranging from 1% to 10% and included
      pseudoarthrosis (9%), nonunion and revision (3%) and screw removal (1%).
      CONCLUSION:  There is low evidence suggesting that patients with axial neck pain
      without radicular or myelopathic symptoms may receive some improvement in pain
      and function following ACDF. However, whether this benefit is greater than
      nontreatment or other treatments cannot be determined with the present
      literature.

PMID- 22956929
TI  - Rating an academic journal-indexing and impact factor.

PMID- 22956928
TI  - Brachial plexus injury mimicking a spinal-cord injury.
AB  - OBJECTIVE:  High-energy impact to the head, neck, and shoulder can result in
      cervical spine as well as brachial plexus injuries. Because cervical spine
      injuries are more common, this tends to be the initial focus for management. We
      present a case in which the initial magnetic resonance imaging (MRI) was somewhat
      misleading and a detailed neurological exam lead to the correct diagnosis.
      CLINICAL PRESENTATION:  A 19-year-old man presented to the hospital following a
      shoulder injury during football practice. The patient immediately complained of
      significant pain in his neck, shoulder, and right arm and the inability to move
      his right arm. He was stabilized in the field for a presumed cervical-spine
      injury and transported to the emergency department. INTERVENTION:  Initial
      radiographic assessment (C-spine CT, right shoulder x-ray) showed no bony
      abnormality. MRI of the cervical-spine showed T2 signal change and cord swelling
      thought to be consistent with a cord contusion. With adequate pain control, a
      detailed neurological examination was possible and was consistent with an upper
      brachial plexus avulsion injury that was confirmed by CT myelogram. The patient
      failed to make significant neurological recovery and he underwent spinal
      accessory nerve grafting to the suprascapular nerve to restore shoulder abduction
      and external rotation, while the phrenic nerve was grafted to the
      musculocutaneous nerve to restore elbow flexion. CONCLUSION:  Cervical spinal
      cord injuries and brachial plexus injuries can occur by the same high energy
      mechanisms and can occur simultaneously. As in this case, MRI findings can be
      misleading and a detailed physical examination is the key to diagnosis. However,
      this can be difficult in polytrauma patients with upper extremity injuries, head
      injuries or concomitant spinal-cord injury. Finally, prompt diagnosis and early
      surgical renerveration have been associated with better long-term recovery with
      certain types of injury.

PMID- 22956930
TI  - Loss to follow-up.

PMID- 22956931
TI  - Evidence-based medicine (EBM): origins and modern application to spine care.

PMID- 22956932
TI  - Long-term outcome of surgical correction of congenital kyphosis in patients with
      myelomeningocele (MMC) with segmental spino-pelvic fixation.
AB  - STUDY DESIGN: A retrospective case series of patients with myelomeningocele (MMC)
      who underwent kyphectomy and posterior segmental fixation using Luque rods and 16
      gauge wires. OBJECTIVE: To assess outcomes after posterior kyphectomy and
      segmental fixation for kyphosis in patients with MMC. METHODS: Thirteen
      consecutive patients who underwent posterior kyphectomy for transforaminal
      fixation contiguous to "everted lamina." Fusion rates, time to fusion, change in
      Cobb angle, complications, and improvement in activities of daily living using
      the Katz score were measured. RESULTS: Average age at time of surgery was 9.2
      (range, 4.5-17) years. Average time to follow-up was 120 (range, 20-310) months.
      Solid fusion was achieved in 9 patients (69%) with a mean time to fusion of 12
      months. The mean postoperative kyphotic curve was 22 degrees  with an average
      correction of 90 degrees . Five patients (38%) experienced a postoperative
      complication. The mean improvement in activities of daily living score was 1.6
      points and all patients achieved independent sitting balance. CONCLUSION:
      Segmental spino-pelvic fixation is a solid alternative mode of fixation in
      patients with MMC with congenital kyphosis. Patient selection, proper
      perioperative multidisciplinary assessment, and surgeons' expertise are
      significant in the success of this complex surgery.METHODS evaluation and class
      of evidence (CoE)STUDY DESIGN: Prospective cohort Retrospective cohort Case
      control Case series*METHODS Patients at similar point in course of treatment*
      Follow-up >= 85%* Similarity of treatment protocols for patient groups* Patients
      followed-up long enough for outcomes to occur Control for extraneous risk
      factorsOverall class of evidenceIVThe definiton of the different classes of
      evidence is available on page 63.

PMID- 22956933
TI  - Vertebral compression model and comparison of augmentation agents.
AB  - STUDY DESIGN: Biomechanical study. OBJECTIVES: To evaluate the compression
      strengths of various bone fillers used in treating vertebral compression
      fractures using a third-generation sawbone model and to evaluate the viability of
      this novel model as an alternative to actual human or animal vertebrae for
      biomechanical testing of vertebral-filling materials. METHODS: Cavities were
      created in the osteoporotic vertebral body sawbone models and filled with PMMA,
      SRS, MIIGX3 HiVisc, and BoneSource fillers. These were cured according to
      manufacturers' recommendations and then tested to failure in the compression
      model. Elastic modulus was calculated and compared with the control group which
      was not augmented. RESULTS: The mean modulus of elasticity for the control group
      vertebrae was 92.44 +/- 19.28 MPa. The mean modulus of elasticity was highest in
      the polymethylmethacrylate (PMMA) group (195.47 +/- 2.33 MPa) and lowest in the
      MIIG group (25.79 +/- 4.77 MPa). The results for the SRS-tricalcium phosphate
      group (79.14 +/- 20.20 MPa) were closest to the control group, followed by the
      BoneSource group (57.49 +/- 8.35 MPa). Statistical analysis, for comparison of
      individual group means, identified significant differences between the control
      group and all other groups (P < .05), with the exception of the SRS-tricalcium
      phosphate group (P = .65, versus control). The modulus of elasticity for the PMMA
      group was significantly higher than all other groups (P < .001). CONCLUSION: The
      third-generation osteoporotic sawbones model simulates in vitro physiological
      specimen function. It was effective for comparing which osteoconductive agents
      may provide adequate strength while minimizing potential adjacent level fracture.
      Increased stiffness was seen with PMMA compared with the unaugmented control as
      well as with calcium phosphate or calcium sulfate cements suggesting that these
      may reduce adjacent segment fractures.

PMID- 22956935
TI  - Spinal cord injury and quality of life: a systematic review of outcome measures.
AB  - STUDY DESIGN: Systematic review. STUDY RATIONALE: According to current estimates,
      there are more than 1 million people living with a spinal cord injury (SCI) in
      the United States alone. Given the potentially devastating impact of SCI on
      health-related quality of life (QoL), we sought to gain an improved understanding
      of QoL outcomes in SCI. OBJECTIVE: To identify and describe common QoL outcomes
      measures in patients with SCI. METHODS: A systematic review of the English
      language literature was undertaken for articles published from 1998 through
      December 2010. Electronic databases and reference lists of key articles were
      searched to identify measures or indices used to evaluate QoL outcomes in
      patients with SCI. The titles and abstracts of the SCI peer-reviewed literature
      were searched to determine which of these outcome measures were most commonly
      used to evaluate QoL in patients with SCI. RESULTS: We identified 27 outcome
      measures used to evaluate QoL in patients with SCI. In SCI literature, the six
      most commonly used objective outcome measures were the Short-form 36 (SF-36);
      Craig Handicap Assessment and Reporting Technique (CHART); Short-form 12 (SF-12);
      Sickness Impact Profile (SIP68); Reintegration to Normal Living Index (RNL); and
      Community Integration Questionnaire (CIQ). The six subjective measures that were
      most frequently used were the Satisfaction with Life Scale (SWLS); Quality of
      Life Index (QLI); Life Satisfaction Questionnaire (LISAT-9/-1); World Health
      Organization Quality of Life-BREF scale (WHOQOL-BREF); Perceived Quality of Life
      (PQOL); and global QoL. All six objective measures have been validated in an SCI
      population, and four of the six subjective measures have been similarly
      validated. Three of each of the objective and subjective measures have been
      reliability tested in a population with SCI. CONCLUSION: In addition to
      neurological and functional changes after SCI, QoL outcomes should be routinely
      assessed. Choice of appropriate QoL measure should be influenced by the study
      objectives and design, as well as the psychometric properties of the particular
      measure within the context of SCI.

PMID- 22956934
TI  - Biological intervertebral disc replacement: an in vivo model and comparison of
      two surgical techniques to approach the rat caudal disc.
AB  - STUDY DESIGN: Prospective randomized animal study. OBJECTIVE: To determine a
      surgical technique for reproducible and functional intervertebral disc
      replacement in an orthotopic animal model. METHODS: The caudal 3/4 intervertebral
      disc (IVD) of the rat tail was approached by two surgical techniques: blunt
      dissection, stripping and retracting (Technique 1) or incising and repairing
      (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was
      dissected and removed, and then either discarded or reinserted. Outcome measures
      were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2
      sequences for measurement of disc space height (DSH) and disc hydration).
      Microcomputed tomographic imaging (micro CT) was additionally performed
      postmortem. RESULTS: No vascular injuries occurred and no systemic or local
      infections were observed over the course of 1 month. Tail movements were
      maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with
      both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH
      with IVD reinsertion but not without. The DSH was demonstrated on MRI
      measurement. A new scoring system to assess IVD appearances was described.
      CONCLUSIONS: The rat tail model, with a tendon dividing surgical technique, can
      function as an orthotopic animal model for IVD research. Mechanical stimulation
      is maintained by preserved tail movements. 7T MRI is a feasible modality for
      longitudinal monitoring for the rat caudal disc.

PMID- 22956936
TI  - Efficacy of interspinous device versus surgical decompression in the treatment of
      lumbar spinal stenosis: a modified network analysis.
AB  - STUDY DESIGN: Systematic review using a modified network analysis. OBJECTIVES: To
      compare the effectiveness and morbidity of interspinous-device placement versus
      surgical decompression for the treatment of lumbar spinal stenosis. SUMMARY:
      Traditionally, the most effective treatment for degenerative lumbar spinal
      stenosis is through surgical decompression. Recently, interspinous devices have
      been used in lieu of standard laminectomy. METHODS: A review of the English
      language literature was undertaken for articles published between 1970 and March
      2010. Electronic databases and reference lists of key articles were searched to
      identify studies comparing surgical decompression with interspinous-device
      placement for the treatment of lumbar spinal stenosis. First, studies making the
      direct comparison (cohort or randomized trials) were searched. Second, randomized
      controlled trials (RCTs) comparing each treatment to conservative management were
      searched to allow for an indirect comparison through a modified network analysis
      approach. Comparison studies involving simultaneous decompression with placement
      of an interspinous device were not included. Studies that did not have a
      comparison group were not included since a treatment effect could not be
      calculated. Two independent reviewers assessed the strength of evidence using the
      GRADE criteria assessing quality, quantity, and consistency of results. The
      strengths of evidence for indirect comparisons were downgraded. Disagreements
      were resolved by consensus. RESULTS: We identified five studies meeting our
      inclusion criteria. No RCTs or cohort studies were identified that made the
      direct comparison of interspinous-device placement with surgical decompression.
      For the indirect comparison, three RCTs compared surgical decompression to
      conservative management and two RCTs compared interspinous-device placement to
      conservative management. There was low evidence supporting greater treatment
      effects for interspinous-device placement compared to decompression for
      disability and pain outcomes at 12 months. There was low evidence demonstrating
      little to no difference in treatment effects between the groups for walking
      distance and complication rates. CONCLUSION: The indirect treatment effect for
      disability and pain favors the interspinous device compared to decompression. The
      low evidence suggests that any further research is very likely to have an
      important impact on the confidence in the estimate of effect and is likely to
      change the estimate. No significant treatment effect differences were observed
      for postoperative walking distance improvement or complication rates; however,
      findings should be considered with caution because of indirect comparisons and
      short follow-up periods.

PMID- 22956937
TI  - Spinal cord compression secondary to intrathecal catheter-induced granuloma: a
      report of four cases.
AB  - OBJECTIVE: The management of nonmalignant pain by morphine pump implantation has
      become an effective and increasingly frequent strategy of care. We report a rare
      complication of intrathecal granuloma formation adjacent to the intrathecal
      catheter tip resulting in spinal cord compression in four patients undergoing
      intrathecal treatment for chronic pain. METHODS: Four patients presented with
      chronic back pain and lower extremity pain and weakness and were treated with
      morphine pump implantation (Fig 1). Each patient developed a mass at the level of
      the intrathecal catheter tip resulting in increased back pain and diminished
      neurological function. Following clinical examination and x-ray workup, the
      patients underwent surgical resection of the mass and removal of the intrathecal
      catheter. One patient received conservative saline therapy first, and another
      patient had granuloma resection first and removal of the intrathecal catheter at
      a later date. Pathological analysis showed granulation tissue with extensive
      necrosis and chronic inflammation, with negative culture results. No evidence of
      neoplasm was found. RESULTS: Patients showed varying degrees of improvement
      following removal of the intrathecal mass. Two patients had moderate pain
      reduction following resection of the granuloma; a third had minimal pain
      improvement; and a fourth had significant pain improvement but continued lower
      extremity weakness. CONCLUSIONS: The formation of granulomas caused by
      intrathecal catheter implantation is a rare but serious complication. Imaging
      studies including magnetic resonance imaging with contrast and computed
      tomography with myelogram should be used to follow up a neurological examination
      consistent with spinal cord compression. Timely surgical intervention may result
      in marked improvement of symptoms.

PMID- 22956939
TI  - Colorectal cancer screening.

PMID- 22956938
TI  - Barrier-restoring therapies in atopic dermatitis: current approaches and future
      perspectives.
AB  - Atopic dermatitis is a multifactorial, chronic relapsing, inflammatory disease,
      characterized by xerosis, eczematous lesions, and pruritus. The latter usually
      leads to an "itch-scratch" cycle that may compromise the epidermal barrier. Skin
      barrier abnormalities in atopic dermatitis may result from mutations in the gene
      encoding for filaggrin, which plays an important role in the formation of
      cornified cytosol. Barrier abnormalities render the skin more permeable to
      irritants, allergens, and microorganisms. Treatment of atopic dermatitis must be
      directed to control the itching, suppress the inflammation, and restore the skin
      barrier. Emollients, both creams and ointments, improve the barrier function of
      stratum corneum by providing it with water and lipids. Studies on atopic
      dermatitis and barrier repair treatment show that adequate lipid replacement
      therapy reduces the inflammation and restores epidermal function. Efforts
      directed to develop immunomodulators that interfere with cytokine-induced skin
      barrier dysfunction, provide a promising strategy for treatment of atopic
      dermatitis. Moreover, an impressive proliferation of more than 80 clinical
      studies focusing on topical treatments in atopic dermatitis led to growing
      expectations for better therapies.

PMID- 22956942
TI  - Celiac disease.

PMID- 22956940
TI  - Psychopharmacological treatment and psychological interventions in irritable
      bowel syndrome.
AB  - Irritable bowel syndrome (IBS) accounts for 25% of gastroenterology output
      practice, making it one of the most common disorders in this practice.
      Psychological and social factors may affect the development of this chronic
      disorder. Furthermore, psychiatric symptoms and psychiatric diseases are highly
      prevalent in this condition, but the approach to treating these is not always
      straightforward. As emphasized in the biopsychosocial model of IBS, with regard
      to the modulatory role of stress-related brain-gut interactions and association
      of the disease with psychological factors and emotional state, it proves useful
      to encourage psychopharmacological treatments and psychosocial therapies, both
      aiming at reducing stress perception. The aim of this paper is to analyze the
      effectiveness of psychopharmacological treatment and psychological interventions
      on irritable bowel syndrome.

PMID- 22956941
TI  - Laparoscopic Diagnosis and Laparoscopic Hyperthermic Intraoperative
      Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Detected by CT
      Examination.
AB  - Background. Patients with early stage of pseudomyxoma peritonei (PMP) are
      sometimes difficult to diagnose the primary sites and intraperitoneal spread of
      tumor and to perform a cytological study. Methods. Patients without a definitive
      diagnosis and with unknown extent of peritoneal spread of tumor underwent
      laparoscopy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) was
      administered as part of the same intervention. The results of treatment were
      evaluated at the time of second-look laparotomy (SLL) as a subsequent
      intervention. Results. Eleven patients were managed by diagnostic laparoscopy
      followed by laparoscopic HIPEC (LHIPEC). The operation time of laparoscopic
      examination and LHIPEC was 177 +/- 26 min (range 124-261 min). No intraoperative
      complication was experienced. The peritoneal carcinomatosis index (PCI) score by
      laparoscopic observation was 16.5 +/- 6.4 (range 0-30). One patient with
      localized pseudomyxoma peritonei (PMP) mucocele did not received LHIPEC; the
      other 10 patients with peritoneal metastases (PM) were treated with LHIPEC. After
      LHIPEC, ascites disappeared in 2 cases and decreased in the amount in the other 8
      cases. Nine patients underwent SLL and cytoreductive surgery (CRS) combined with
      HIPEC. The duration between LHIPEC and SLL ranged from 40 to 207 days (97 +/- 40
      days). The PCI at the SLL ranged from 4 to 27 (12.9 +/- 7.1). The PCI at the time
      of SLL decreased as compared to PCI at the time of diagnostic laparotomy in 7 of
      9 patients. Median follow-up period is 22 months (range 7-35). All 11 patients
      are alive. Conclusion. The early results suggest that laparoscopic diagnosis
      combined with LHIPEC is useful to determine the surgical treatment plan and
      reduce the tumor burden before definitive CRS at SLL.

PMID- 22956943
TI  - Peyronie's Disease: Still a Surgical Disease.
AB  - Peyronie's Disease (PD) remains a challenging and clinically significant morbid
      condition. Since its first description by Francois Gigot de la Peyronie, much of
      the treatment for PD remains nonstandardized. PD is characterized by the
      formation of fibrous plaques at the level of the tunica albuginea. Clinical
      manifestations include morphologic changes, such as curvatures and hourglass
      deformities. Here, we review the common surgical techniques for the management of
      patients with PD.

PMID- 22956945
TI  - Do we need new personalized emergency telehealth solutions? A survey of 100
      emergency department patients and a first report of the swiss limmex emergency
      wristwatch: an original study.
AB  - Development of new personal mobile and wireless devices for healthcare has become
      essential due to our aging population characterized by constant rise in chronic
      diseases that consequently require a complex treatment and close monitoring.
      Personal telehealth devices allow patients to adequately receive their
      appropriate treatment, followup with their doctors, and report any emergency
      without the need of the presence of any caregivers with them thus increasing
      their quality of life in a cost-effective fashion. This paper includes a brief
      overview of personal telehealth systems, a survey of 100 consecutive ED patients
      aged >65 years, and introduces "Limmex" a new GSM based technology packaged in a
      wristwatch. Limmex can by a push of a button initiate multiple emergency call and
      establish mobile communication between the patient and a preselected person,
      institution, or a search and rescue service. To the best of our knowledge, Limmex
      is the first of its kind worldwide.

PMID- 22956946
TI  - Are Dementia Patient's Engagement Using Tailored Stimuli the Same? The Apathy
      Dilemma in Nursing Home Residents.
AB  - Background. Apathy is the most frequent behavioural disturbance understanding how
      apathy drives engagement in resident's activities of interests is a milestone to
      better understanding and tailored challenging interventions targeting engagement
      enhancement. Method. Residents aged 60 and older with dementia according to the
      ICD 10 from four nursing homes in the south east of France. A set of 25 stimuli
      were used and categorized by participant into Work, Leisure, Family, or Personal
      categories, an additional "not interested" category was used for comparison of
      engagement. The participants stimuli allocation was randomized in guided and
      unguided situations over a two-week period with 15minute interaction for each
      stimulus (n = 2) of each category (5*(15 min*2)). Clinical trial identifier:
      NCT01314131. Results. The mean age, 95% confidence interval (CI) of the 40
      participants was 85.4 (83.8-87) with a mean MMSE score, CI95% of 17.7 (16.5-19).
      Analyses revealed a significant superiority effect of guidance over unguided
      interaction in duration of engagement in all categories of interest except for
      the stimulus category "family" and all P < .05. Apathetic participants when
      guided had longer engagement duration in stimulus Leisure and Personal (all P <
      .01). Conclusion. Guidance and better activities of interest can lead to enhanced
      engagement time in participants with dementia.

PMID- 22956947
TI  - Characterization of former gestational diabetes mellitus: prognostic,
      therapeutic, and predictive aspects.

PMID- 22956948
TI  - Prevention and early detection of head and neck squamous cell cancers.

PMID- 22956944
TI  - Biomarker-based targeting of the androgen-androgen receptor axis in advanced
      prostate cancer.
AB  - Recent therapeutic advances for managing advanced prostate cancer include the
      successful targeting of the androgen-AR axis with several new drugs in castrate
      resistant prostate cancer including abiraterone acetate and enzalutamide
      (MDV3100). This translational progress from "bench to bed-side" has resulted in
      an enlarging repertoire of novel and traditional drug choices now available for
      use in advanced prostate cancer therapeutics, which has had a positive clinical
      impact in prolonging longevity and quality of life of advanced prostate cancer
      patients. In order to further the clinical utility of these drugs, development of
      predictive biomarkers guiding individual therapeutic choices remains an ongoing
      challenge. This paper will summarize the potential in developing predictive
      biomarkers based on the pathophysiology of the androgen-AR axis in tumor tissue
      from patients with advanced prostate cancer as well as inherited variation in the
      patient's genome. Specific examples of rational clinical trial designs
      incorporating potential predictive biomarkers from these pathways will illustrate
      several aspects of pharmacogenetic and pharmacogenomic predictive biomarker
      development in advanced prostate cancer therapeutics.

PMID- 22956949
TI  - A systematic review of barriers to breast cancer care in developing countries
      resulting in delayed patient presentation.
AB  - Background. Within the developing world, many personal, sociocultural, and
      economic factors cause delayed patient presentation, a prolonged interval from
      initial symptom discovery to provider presentation. Understanding these barriers
      to care is crucial to optimizing interventions that pre-empt patient delay.
      Methods. A systematic review was conducted querying: PubMed, Embase, Web of
      Science, CINAHL, Cochrane Library, J East, CAB, African Index Medicus, and
      LiLACS. Of 763 unique abstracts, 122 were extracted for full review and 13
      included in final analysis. Results. Studies posed variable risks of bias and
      produced mixed results. There is strong evidence that lower education level and
      lesser income status contribute to patient delay. There is weaker and, sometimes,
      contradictory evidence that other factors may also contribute. Discussion.
      Poverty emerges as the underlying common denominator preventing earlier
      presentation in these settings. The evidence for sociocultural variables is less
      strong, but may reflect current paucity of high-quality research. Conflicting
      results may be due to heterogeneity of the developing world itself. Conclusion.
      Future research is required that includes patients with and without delay,
      utilizes a validated questionnaire, and controls for potential confounders.
      Current evidence suggests that interventions should primarily increase proximal
      and affordable healthcare access and secondarily enhance breast cancer awareness,
      to productively reduce patient delay.

PMID- 22956950
TI  - Initial In Vivo Quantification of Tc-99m Sestamibi Uptake as a Function of Tissue
      Type in Healthy Breasts Using Dedicated Breast SPECT-CT.
AB  - A pilot study is underway to quantify in vivo the uptake and distribution of Tc
      99m Sestamibi in subjects without previous history of breast cancer using a
      dedicated SPECT-CT breast imaging system. Subjects undergoing diagnostic
      parathyroid imaging studies were consented and imaged as part of this IRB
      approved breast imaging study. For each of the seven subjects, one randomly
      selected breast was imaged prone-pendant using the dedicated, compact breast
      SPECT-CT system underneath the shielded patient support. Iteratively
      reconstructed and attenuation and/or scatter corrected images were coregistered;
      CT images were segmented into glandular and fatty tissue by three different
      methods; the average concentration of Sestamibi was determined from the SPECT
      data using the CT-based segmentation and previously established quantification
      techniques. Very minor differences between the segmentation methods were
      observed, and the results indicate an average image-based in vivo Sestamibi
      concentration of 0.10 +/- 0.16 MUCi/mL with no preferential uptake by glandular
      or fatty tissues.

PMID- 22956951
TI  - N-Acetyltransferase 1 (NAT1) Genotype: A Risk Factor for Urinary Bladder Cancer
      in a Lebanese Population.
AB  - In Lebanon, bladder cancer is the second most incident cancer among men. This
      study investigates a possible association between N-acetyltransferase 1 (NAT1)
      genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese
      men. A case-control study (54 cases and 105 hospital-based controls) was
      conducted in two major hospitals in Beirut. Cases were randomly selected from
      patients diagnosed in the period of 2002-2008. Controls were conveniently
      identified and selected from the same settings. Data was collected using
      interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR
      RFLP. Statistical analysis revolved around univariate, bivariate, and
      multivariate logistic regression models, along with checks for effect
      modification. Results showed NAT1(*)14A allele, smoking, occupational exposure to
      combustion fumes, and prostate-related symptoms, to be risk factors for bladder
      cancer. The odds of carrying at least one NAT1(*)14A allele are 7 times higher in
      cases compared to controls (OR = 7.86, 95% CI: 1.53-40.39). A gene-environment
      interaction was identified for NAT1(*)14A allele with occupational exposure to
      combustion fumes. Among carriers of NAT1(*)14A allele, the odds of bladder cancer
      dropped to 2.03 from 3.72. Our study suggests NAT1(*)14A allele as a possible
      biomarker for bladder cancer. Further research is recommended to confirm this
      association.

PMID- 22956952
TI  - Transcriptome-wide detection of differentially expressed coding and non-coding
      transcripts and their clinical significance in prostate cancer.
AB  - Prostate cancer is a clinically and biologically heterogeneous disease.
      Deregulation of splice variants has been shown to contribute significantly to
      this complexity. High-throughput technologies such as oligonucleotide microarrays
      allow for the detection of transcripts that play a role in disease progression in
      a transcriptome-wide level. In this study, we use a publicly available dataset of
      normal adjacent, primary tumor, and metastatic prostate cancer samples (GSE21034)
      to detect differentially expressed coding and non-coding transcripts between
      these disease states. To achieve this, we focus on transcript-specific probe
      selection regions, that is, those probe sets that correspond unambiguously to a
      single transcript. Based on this, we are able to pinpoint at the transcript
      specific level transcripts that are differentially expressed throughout prostate
      cancer progression. We confirm previously reported cases and find novel
      transcripts for which no prior implication in prostate cancer progression has
      been made. Furthermore, we show that transcript-specific differential expression
      has unique prognostic potential and provides a clinically significant source of
      biomarker signatures for prostate cancer risk stratification. The results
      presented here serve as a catalog of differentially expressed transcript-specific
      markers throughout prostate cancer progression that can be used as basis for
      further development and translation into the clinic.

PMID- 22956953
TI  - Chronic Diseases among Older Cancer Survivors.
AB  - Objective. To compare the occurrence of pre-existing and subsequent comorbidity
      among older cancer patients (>=60 years) with older non-cancer patients. Material
      and Methods. Each cancer patient (n = 3835, mean age 72) was matched with four
      non-cancer patients in terms of age, sex, and practice. The occurrence of chronic
      diseases was assessed cross-sectionally (lifetime prevalence at time of
      diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients
      and for breast, prostate, and colorectal cancer patients separately. Cancer and
      non-cancer patients were compared using logistic and Cox regression analysis.
      Results. The occurrence of the most common pre-existing and incident chronic
      diseases was largely similar in cancer and non-cancer patients, except for pre
      existing COPD (OR 1.21, 95% CI 1.06-1.37) and subsequent venous thrombosis in the
      first two years after cancer diagnosis (HR 4.20, 95% CI 2.74-6.44), which were
      significantly more frequent (P < 0.01) among older cancer compared to non-cancer
      patients. Conclusion. The frequency of multimorbidity in older cancer patients is
      high. However, apart from COPD and venous thrombosis, the incidence of chronic
      diseases in older cancer patients is similar compared to non-cancer patients of
      the same age, sex, and practice.

PMID- 22956954
TI  - Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute
      Hantavirus Pulmonary Syndrome.
AB  - Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia,
      and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced
      by hypoxia, potently induces vascular permeability, and is associated with high
      altitude-induced pulmonary edema. Hantaviruses alter the normal regulation of
      beta3 integrins that restrict VEGF-directed permeability and hantavirus infected
      endothelial cells are hyperresponsive to the permeabilizing effects of VEGF.
      However, the role of VEGF in acute pulmonary edema observed in HPS patients
      remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema
      fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in
      HPS patients PEF compared to controls with the highest levels observed in PEF
      samples from a fatal HPS case. VEGF levels were highest in PBMC samples during
      the first five days of hospitalization and diminished during recovery.
      Significantly increased PEF and PBMC VEGF levels are consistent with acute
      pulmonary edema observed in HPS patients and HPS disease severity. We observed
      substantially lower VEGF levels in a severe HPS disease survivor after
      extracorporeal membrane oxygenation. These findings suggest the importance of
      patients' VEGF levels during HPS, support the involvement of VEGF responses in
      HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic
      approach.

PMID- 22956955
TI  - Impact of Image Filters and Observations Parameters in CBCT for Identification of
      Mandibular Osteolytic Lesions.
AB  - The aim of this study was to analyze the influence of filters (algorithms) to
      improve the image of Cone Beam Computed Tomography (CBCT) in diagnosis of
      osteolytic lesions of the mandible, in order to establish the protocols for
      viewing images more suitable for CBCT diagnostics. 15 dry mandibles in which
      perforations were performed, simulating lesions, were submitted to CBCT
      examination. Two examiners analyzed the images, using filters to improve image
      Hard, Normal, and Very Sharp, contained in the iCAT Vision software, and
      protocols for assessment: axial; sagittal and coronal; and axial, sagittal and
      coronal planes simultaneously (MPR), on two occasions. The sensitivity and
      specificity (validity) of the cone beam computed tomography (CBCT) have been
      demonstrated as the values achieved were above 75% for sensitivity and above 85%
      for specificity, reaching around 95.5% of sensitivity and 99% of specificity when
      we used the appropriate observation protocol. It was concluded that the use of
      filters (algorithms) to improve the CBCT image influences the diagnosis, due to
      the fact that all measured values were correspondingly higher when it was used
      the filter Very Sharp, which justifies its use for clinical activities, followed
      by Hard and Normal filters, in order of decreasing values.

PMID- 22956956
TI  - Mineralization Potential of Electrospun PDO-Hydroxyapatite-Fibrinogen Blended
      Scaffolds.
AB  - The current bone autograft procedure for cleft palate repair presents several
      disadvantages such as limited availability, additional invasive surgery, and
      donor site morbidity. The present preliminary study evaluates the mineralization
      potential of electrospun polydioxanone:nano-hydroxyapatite : fibrinogen (PDO :
      nHA : Fg) blended scaffolds in different simulated body fluids (SBF). Scaffolds
      were fabricated by blending PDO : nHA : Fg in the following percent by weight
      ratios: 100 : 0 : 0, 50 : 25 : 25, 50 : 50 : 0, 50 : 0 : 50, 0 : 0 : 100, and 0 :
      50 : 50. Samples were immersed in (conventional (c), revised (r), ionic (i), and
      modified (m)) SBF for 5 and 14 days to induce mineralization. Scaffolds were
      characterized before and after mineralization via scanning electron microscopy,
      Alizarin Red-based assay, and modified burnout test. The addition of Fg resulted
      in scaffolds with smaller fiber diameters. Fg containing scaffolds also induced
      sheet-like mineralization while individual fiber mineralization was noticed in
      its absence. Mineralized electrospun Fg scaffolds without PDO were not
      mechanically stable after 5 days in SBF, but had superior mineralization
      capabilities which produced a thick bone-like mineral (BLM) layer throughout the
      scaffolds. 50 : 50 : 0 scaffolds incubated in either r-SBF for 5 days or c-SBF
      for 14 days produced scaffolds with high mineral content and individual
      mineralized fibers. These mineralized scaffolds were still porous and will be
      further optimized as an effective bone substitute in future studies.

PMID- 22956957
TI  - Next generation orthopaedic implants by additive manufacturing using electron
      beam melting.
AB  - This paper presents some examples of knee and hip implant components containing
      porous structures and fabricated in monolithic forms utilizing electron beam
      melting (EBM). In addition, utilizing stiffness or relative stiffness versus
      relative density design plots for open-cellular structures (mesh and foam
      components) of Ti-6Al-4V and Co-29Cr-6Mo alloy fabricated by EBM, it is
      demonstrated that stiffness-compatible implants can be fabricated for optimal
      stress shielding for bone regimes as well as bone cell ingrowth. Implications for
      the fabrication of patient-specific, monolithic, multifunctional orthopaedic
      implants using EBM are described along with microstructures and mechanical
      properties characteristic of both Ti-6Al-4V and Co-29Cr-6Mo alloy prototypes,
      including both solid and open-cellular prototypes manufactured by additive
      manufacturing (AM) using EBM.

PMID- 22956958
TI  - Selective types of autophagy.

PMID- 22956960
TI  - Lipopolysaccharide-Induced Cellular Activation May Participate in the
      Immunopathogenesis of Visceral Leishmaniasis Alone or in HIV Coinfection.
AB  - Visceral Leishmaniasis (VL) is an infectious disease which constitutes a serious
      public health problem, integrating the list of neglected tropical diseases. The
      disease is characterized by a Leishmania-specific immune suppression T-cell
      depletion and a decrease of other hematopoietic cells. In parallel, an
      immunostimulatory response also occurs, represented by polyclonal B lymphocytes,
      T-cell activation, and systemic proinflammatory responses. Parasite antigens were
      believed to mediate both suppression and activation mechanisms, but these
      concepts are constantly being revised. Similar to reports on HIV/AIDS, we have
      proposed that gut parasitation by amastigotes and lymphocyte depletion could also
      affect gut-associated lymphoid tissue, leading to mucosal barrier breach and
      predisposing to microbial translocation. An increment of plasmatic
      lipopolysaccharide (LPS) levels observed in Brazilian VL patients was implicated
      in the reduced blood CD4(+) and CD8(+) T cell counts, systemic T-cell activation,
      pro-inflammatory cytokines and MIF plasma levels, suggesting that a bacterial
      molecule not associated with Leishmania infection can exert deleterious effects
      on immune system. Recent results also pointed that the proinflammatory response
      was potentiated in VL/HIV-AIDS coinfected patients. The LPS-mediated cell
      activation adds another concept to the immunopathogenesis of VL and can bring a
      rational for new therapeutic interventions that could ameliorate the management
      of these patients.

PMID- 22956959
TI  - Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its
      Relevance to Neurodegenerative Diseases.
AB  - Debilitating neurodegenerative diseases, such as Alzheimer's disease (AD) and
      Parkinson's disease (PD), can be attributed to neuronal cell damage in specific
      brain regions. An important hallmark of these diseases is increased oxidative and
      nitrosative stress that occurs via overproduction of highly reactive free
      radicals known as reactive oxygen species (ROS) and reactive nitrogen species
      (RNS). These molecules are normally removed by cellular antioxidant systems.
      Under physiological conditions, ROS/RNS are present at low levels, mediating
      several neurotrophic and neuroprotective signaling pathways. In contrast, under
      pathological conditions, there is a pronounced increase in ROS/RNS generation,
      impairing normal neurological function. Nitric oxide (NO) is one such molecule
      that functions as a signaling agent under physiological conditions but causes
      nitrosative stress under pathological conditions due to its enhanced production.
      As first reported by our group and colleagues, the toxic effects of NO can be in
      part attributed to thiol S-nitrosylation, a posttranslational modification of
      cysteine residues on specific proteins. Here, we review several reports appearing
      over the past decade showing that S-nitrosylation of an increasing number of
      proteins compromises important cellular functions, including mitochondrial
      dynamics, endoplasmic reticulum (ER) protein folding, and signal transduction,
      thereby promoting synaptic damage, cell death, and neurodegeneration.

PMID- 22956961
TI  - Differential Adaptations of Methicillin-Resistant Staphylococcus aureus to Serial
      In Vitro Passage in Daptomycin: Evolution of Daptomycin Resistance and Role of
      Membrane Carotenoid Content and Fluidity.
AB  - Previous studies showed serial 20 d in vitro passage of MRSA strain MW2 in
      sublethal daptomycin (DAP) resulted in diverse perturbations in both cell
      membrane (CM) and cell wall (CW) characteristics, including increased CM
      rigidity; increased CW thickness; "gain-in-function" single nucleotide
      polymorphisms (SNPs) in the mprF locus (i.e., increased synthesis and
      translocation of lysyl-phosphatidylglycerol (L-PG)); progressive accumulation of
      SNPs in yyc and rpo locus genes; reduced carotenoid production; cross-resistance
      to innate host defense peptides. The current study was designed to characterize
      the reproducibility of these phenotypic and genotypic modifications following in
      vitro serial passages of the same parental strain. After a second 20d serial in
      vitro passage of parental MW2, emergence of DAP-R was associated with evolution
      of several phenotypes closely mirroring previous passage outcomes. However, in
      contrast to the initial serial passage strain set, we observed (i) only modest
      increase in L-PG synthesis and no increase in L-PG outer CM translocation; (ii)
      significantly increased carotenoid synthesis (P < 0.05); (iii) a different order
      of SNP accumulations (mprF ? rpoB ? yycG); (iv) a different cadre and locations
      of such SNPs. Thus, MRSA strains are not "pre-programmed" to phenotypically
      and/or genotypically adapt in an identical manner during induction of DAP
      resistance.

PMID- 22956962
TI  - Suppression of obsessive-compulsive symptoms after head trauma.
AB  - Obsessive-Compulsive Disorder (OCD) encompasses a spectrum of clinical symptoms
      characterized by unwanted thoughts coupled with an intense compulsion to act and
      to repeat behavior fragments in a ritualistic and stereotyped sequence. Obsessive
      compulsive symptom due to brain lesions is not rare, but suppression of these
      symptoms after head trauma is very rare and we found only 3 cases in review of
      literatures from 1966 to 2001. The case of a patient suffering with severe OCD is
      described of note; her symptoms disappeared following right temporo
      parietofrontal lesion.

PMID- 22956963
TI  - Neuroblastoma in the Elderly and SIADH: Case Report and Review of the Literature.
AB  - Objective. To report the rare case of a thymic neuroblastoma, in an elderly woman
      with SIADH at presentation. Methods. Clinical and biochemical data of the patient
      are presented and the pertinent literature is reviewed. Results. a 79-year-old
      woman was admitted into our department with worsening asthenia, severe
      hyponatremia (114.8 mEq/L), low plasma osmolarity (253 mEq/L), and inappropriate
      urinary sodium concentration (151 mEq/L). CT scan showed an a large solid
      inhomogeneous mass in the anterior mediastinum. (18)F-FDG-PET/CT showed uptake in
      the mass. On continuous 3% hypertonic saline infusion, sodium gradually increased
      without achieving normal values. The patient underwent surgery, followed by full
      normalization of sodium levels. Tumor cells were positive for neuroendocrine
      markers. Thymic neuroblastoma with SIADH was diagnosed. Conclusions.
      Neuroblastoma is an extremely rare tumor in the elderly. Contrary to children and
      younger adults, neuroblastoma in older adults is typically localized in the
      anterior mediastinum and is often associated with SIADH. Moreover, it has mainly
      local aggressiveness in this age group, without metastatic spread; thus radical
      surgery achieves cure in most cases.

PMID- 22956964
TI  - Noncirrhotic Portal Hypertension due to Nodular Regenerative Hyperplasia Treated
      with Surgical Portacaval Shunt.
AB  - Nodular regenerative hyperplasia (NRH) is an uncommon condition, but an important
      cause of noncirrhotic intrahepatic portal hypertension (NCIPH), characterized by
      micronodules of regenerative hepatocytes throughout the liver without intervening
      fibrous septae. Herein, we present a case of a thirty-seven-year-old female with
      systemic lupus erythematosus (SLE) who was discovered to have significant
      esophageal varices on endoscopy for dyspepsia. Her labs revealed a slight
      elevation in the alkaline phosphatase and mild thrombocytopenia. Abdominal MRI
      revealed seven focal hepatic masses, splenomegaly, no ascites, and a patent
      portal vein. Ultrasound-guided core biopsy was reported as focal nodular
      hyperplasia. However, her varices persisted despite treatment with beta-blockers
      and four additional upper endoscopies with banding. She was subsequently referred
      for a surgical opinion. At that time, given her history of SLE, azathioprine use,
      and portal hypertension, suspicion for NRH was raised. Given her normal synthetic
      function and lack of parenchymal liver disease, the patient was offered surgical
      shunting. During shunt surgery, a liver wedge biopsy was also performed and this
      confirmed NRH. An upper endoscopy six weeks after shunting verified complete
      resolution of varices. Currently, fifteen months after surgery duplex
      ultrasonography demonstrates shunt patency and the patient is without recurrence
      of her portal hypertension.

PMID- 22956965
TI  - Pediatric nephrology: highlights for the general practitioner.

PMID- 22956966
TI  - Built environment and its influences on walking among older women: use of
      standardized geographic units to define urban forms.
AB  - Consensus is lacking on specific and policy-relevant measures of neighborhood
      attributes that may affect health outcomes. To address this limitation, we
      created small standardized geographic units measuring the transit, commercial,
      and park area access, intersection, and population density for the Portland,
      Oregon metropolitan area. Cluster analysis was used to identify six unique urban
      forms: central city, city periphery, suburb, urban fringe with poor commercial
      access, urban fringe with pool park access, and satellite city. The urban form
      information was linkable to the detailed physical activity, health, and socio
      demographic data of 2,005 older women without the use of administrative
      boundaries. Evaluation of the relationship between urban forms and walking
      behavior indicates that older women residing in city center were more likely to
      walk than those living in city periphery, suburb communities, and urban fringe
      with poor commercial access; however, these women were not significantly more
      likely to walk compared to those residing in urban fringe with poor park access
      or satellite city. Utility of small standardized geographic units and clusters to
      measure and define built environment support research investigating the impact of
      built environment and health. The findings may inform environmental/policy
      interventions that shape communities and promote active living.

PMID- 22956968
TI  - Rheumatoid factor, complement, and mixed cryoglobulinemia.
AB  - Low serum level of complement component 4 (C4) that occurs in mixed
      cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement
      by the classical pathway. Potential activators include monoclonal IgM rheumatoid
      factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps
      modulated by the rheology and stoichiometry of cryocomplexes in specific
      microcirculations. There is also the potential for activation of complement by
      the alternative and lectin pathways, particularly in the setting of chronic
      infection and immune stimulation caused by hepatitis C virus (HCV). Engagement of
      C1q and interaction with specific cell surface receptors serve to localize immune
      complexes (ICs) to the sites of pathology, notably the cutaneous and glomerular
      microcirculations. Defective or saturated clearance of ICs by CR1and/or Fc
      receptors may explain persistence in the circulation. The phlogistic potential of
      cryoprecipitable ICs depends upon the cleavage of complement components to
      generate fragments with anaphylatoxin or leukocyte mobilizing activity, and the
      assembly of the membrane attack complex (C5b-9) on cell surfaces. A research
      agenda would include further characterization of the effector arm of complement
      activation in MC, and elucidation of activation mechanisms due to virus and viral
      antigens in HCV infection.

PMID- 22956967
TI  - Genetic associations in acquired immune-mediated bone marrow failure syndromes:
      insights in aplastic anemia and chronic idiopathic neutropenia.
AB  - Increasing interest on the field of autoimmune diseases has unveiled a plethora
      of genetic factors that predispose to these diseases. However, in immune-mediated
      bone marrow failure syndromes, such as acquired aplastic anemia and chronic
      idiopathic neutropenia, in which the pathophysiology results from a
      myelosuppressive bone marrow microenvironment mainly due to the presence of
      activated T lymphocytes, leading to the accelerated apoptotic death of the
      hematopoietic stem and progenitor cells, such genetic associations have been very
      limited. Various alleles and haplotypes of human leucocyte antigen (HLA)
      molecules have been implicated in the predisposition of developing the above
      diseases, as well as polymorphisms of inhibitory cytokines such as interferon
      gamma, tumor necrosis factor-alpha, and transforming growth factor-beta1 along
      with polymorphisms on molecules of the immune system including the T-bet
      transcription factor and signal transducers and activators of transcription. In
      some cases, specific polymorphisms have been implicated in the outcome of
      treatment on those patients.

PMID- 22956970
TI  - Indolent B-cell lymphomas associated with HCV infection: clinical and virological
      features and role of antiviral therapy.
AB  - The association between hepatitis C virus (HCV) infection and B-cell non
      Hodgkin's lymphomas (NHL) has been demonstrated by epidemiological studies, in
      particular in highly endemic geographical areas such as Italy, Japan, and
      southern parts of United States. In these countries, together with diffuse large
      B-cell lymphomas, marginal zone lymphomas are the histotypes most frequently
      associated with HCV infection; in Italy around 20-30% cases of marginal zone
      lymphomas are HCV positive. Recently, antiviral treatment with interferon with or
      without ribavirin has been proved to be effective in the treatment of HCV
      positive patients affected by indolent lymphoma, prevalently of marginal zone
      origin. An increasing number of experiences confirmed the validity of this
      approach in marginal zone lymphomas and in other indolent NHL subtypes like
      lymphoplasmacytic lymphoma. Across different studies, overall response rate was
      approximately 75%. Hematological responses resulted significantly associated with
      the eradication of the virus. This is the strongest evidence of a causative link
      between HCV and lymphomas. The aim of this paper is to illustrate the
      relationship between HCV infection and different subtypes of indolent B-cell
      lymphomas and to systematically summarize the data from the therapeutic studies
      that reported the use of antiviral treatment as hematological therapy in patients
      with HCV-associated indolent lymphomas.

PMID- 22956971
TI  - Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis.
AB  - Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand,
      foot, and mouth disease. It can also cause severe complications of the central
      nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe
      complication that can lead to death. EV71 replicates in leukocytes, endothelial
      cells, and dendritic cells resulting in the production of immune and inflammatory
      mediators that shape innate and acquired immune responses and the complications
      of disease. Cytokines, as a part of innate immunity, favor the development of
      antiviral and Th1 immune responses. Cytokines and chemokines play an important
      role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the
      systemic inflammatory responses to infection play important, but distinctly
      different, roles in the pathogenesis of EV71 pulmonary edema. Administration of
      intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been
      shown to modulate inflammation, to reduce sympathetic overactivity, and to
      improve survival in patients with EV71 autonomic nervous system dysregulation and
      pulmonary edema.

PMID- 22956972
TI  - Mitigation of H(2)O(2)-Induced Mitochondrial-Mediated Apoptosis in NG108-15 Cells
      by Novel Mesuagenin C from Mesua kunstleri (King) Kosterm.
AB  - This study was aimed to isolate and evaluate neuroprotective compounds from the
      hexane extract of the bark of Mesua kunstleri (Clusiaceae) on H(2)O(2)-induced
      apoptosis in NG108-15 cells. Five 4-phenylcoumarins were isolated by using
      various chromatographic techniques via neuroprotective activity-guided
      fractionation and isolation from the active hexane extract. The chemical
      structures of the isolated compounds were confirmed by NMR spectroscopic data
      interpretation and comparison with literature values. Cell viability data
      demonstrated that mesuagenin C 3 significantly increased cell viability. Hoechst
      33342/PI staining illustrated mesuagenin C 3 was able to abate the nuclear
      shrinkage, chromatin condensation and formation of apoptotic bodies. Pretreatment
      with mesuagenin C 3 reduced total annexin V positive cells and increased the
      level of intracellular glutathione (GSH). Mesuagenin C 3 attenuated membrane
      potential (Deltapsim), reduced Bax/Bcl-2 ratio and inactivated of caspase-3/7 and
      -9. These results indicated that mesuagenin C 3 could protect NG108-15 cells
      against H(2)O(2)-induced apoptosis by increasing intracellular GSH level,
      aggrandizing Deltapsim, and modulating apoptotic signalling pathway through Bcl-2
      family and caspase-3/7 and -9. These findings confirmed the involvement of
      intrinsic apoptotic pathway in H(2)O(2)-induced apoptosis and suggested that
      mesuagenin C 3 may have potential therapeutic properties for neurodegenerative
      diseases.

PMID- 22956973
TI  - Involvement of the cerebral monoamine neurotransmitters system in antidepressant
      like effects of a chinese herbal decoction, baihe dihuang tang, in mice model.
AB  - Baihe Dihuang Tang (BDT) is a renowned Chinese herbal formula which is commonly
      used for treating patients with mental instability, absentmindedness, insomnia,
      deficient dysphoria, and other psychological diseases. These major symptoms
      closely associated with the depressive disorders. BDT was widely popular use for
      treating emotion-thought disorders for many years in China. In the present study,
      the antidepressant-like effect of BDT in mice was investigated by using the
      forced swim test (FST) and the tail suspension test (TST). The underlying
      mechanism was explored by determining the effect of BDT on the level of cerebral
      monoamine neurotransmitters. BDT (9 and 18 g/kg, p.o. for 14 days) administration
      significantly reduced the immobility time in both the FST and the TST without
      changing locomotion in the open field-test (OFT). Moreover, BDT treatment at the
      dose of 18 g/kg inhibited reserpine-induced ptosis. Meanwhile, BDT enhanced 5-HT
      and NA levels in mouse cerebrum as well as decreased the ratio of 5-HT compared
      to its metabolite, 5-HIAA, (turnover, 5-HIAA/5-HT) after TST. The results
      demonstrated that the antidepressant-like effect of BDT is mediated, at least
      partially, via the central monoaminergic neurotransmitter system.

PMID- 22956974
TI  - Total Saponin from Root of Actinidia valvata Dunn Inhibits Hepatoma 22 Growth and
      Metastasis In Vivo by Suppression Angiogenesis.
AB  - The root of Actinidia valvata dunn has been widely used in the treatment of
      hepatocellular carcinoma (HCC), proved to be beneficial for a longer and better
      life in China. In present work, total saponin from root of Actinidia valvata Dunn
      (TSAVD) was extracted, and its effects on hepatoma H22-based mouse in vivo were
      observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to
      observe TSAVD effect on tumor growth. The microvessel density (MVD), vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) are
      characterized factors of angiogenesis, which were compared between TSAVD-treated
      and control groups. Antimetastasis effect on experimental pulmonary metastasis
      hepatoma mice was also observed in the study. The results demonstrated that TSAVD
      can effectively inhibit HCC growth and metastasis in vivo, inhibit the formation
      of microvessel, downregulate expressions of VEGF and bFGF, and retrain
      angiogenesis of hepatoma 22 which could be one of the reasons.

PMID- 22956975
TI  - Electroacupuncture Confers Antinociceptive Effects via Inhibition of Glutamate
      Transporter Downregulation in Complete Freund's Adjuvant-Injected Rats.
AB  - When we evaluated changes of glial fibrillary acidic protein (GFAP) and two
      glutamate transporter (GTs) by immunohistochemistry, expression of GFAP showed a
      significant increase in complete Freund's adjuvant (CFA)-injected rats; however,
      this expression was strongly inhibited by electroacupuncture (EA) stimulation.
      Robust downregulation of glutamate-aspartate transporter (GLAST) and glutamate
      transporter-1 (GLT-1) was observed in CFA-injected rats; however, EA stimulation
      resulted in recovery of this expression. Double-labeling staining showed co
      localization of a large proportion of GLAST or GLT-1 with GFAP. Using Western
      blot, we confirmed protein expression of two GTs, but no differences in the mRNA
      content of these GTs were observed. Because EA treatment resulted in strong
      inhibition of CFA-induced proteasome activities, we examined the question of
      whether thermal sensitivities and GTs expression could be regulated by proteasome
      inhibitor MG132. CFA-injected rats co-treated with EA and MG132 showed a
      significantly longer thermal sensitivity, compared with CFA-injected rats with or
      without MG132. Both EA and MG132 blocked CFA-induced GLAST and GLT-1
      downregulation within the spinal cord. These results provide evidence for
      involvement of GLAST and GLT-1 in response to activation of spinal astrocytes in
      an EA antinociceptive effect. Antinociceptive effect of EA may be induced via
      proteasome-mediated regulation of spinal GTs.

PMID- 22956977
TI  - Epimedium koreanum Extract and Its Constituent Icariin Improve Motor Dysfunction
      in Spinal Cord Injury.
AB  - Although cell transplantation strategies for spinal cord injury (SCI) using
      sources such as iPS cells and neural stem cells are focused as expectative
      therapies for SCI, the possibility of medication as more accessible and practical
      way should not be given up. We, therefore, aimed to develop medical sources for
      SCI. In this paper, we evaluated effects of a famous tonic herb, Epimedium
      koreanum, on motor dysfunction in spinal cord injury (SCI). The spinal cord was
      injured by contusion after laminectomy at T10 level. Oral administration of the
      methanol extract of E. koreanum significantly enhanced hindlimb function in SCI
      mice by short period treatment (for initial 3 days) and chronic treatment (21
      days), although chronic treatment recovered the function more potently. Since it
      is well known that icariin is the major constituent in E. koreanum, icariin was
      administered orally to SCI mice for initial 3 days. Motor dysfunction was
      ameliorated by icariin treatment similarly to the methanol extract of E.
      koreanum. This paper is the first report to indicate E. koreanum is effective for
      recovery of motor function in SCI, and at least icariin is an active constituent.

PMID- 22956976
TI  - Effects of Low-Dose versus High-Dose gamma-Tocotrienol on the Bone Cells Exposed
      to the Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis.
AB  - Oxidative stress and apoptosis can disrupt the bone formation activity of
      osteoblasts which can lead to osteoporosis. This study was conducted to
      investigate the effects of gamma-tocotrienol on lipid peroxidation, antioxidant
      enzymes activities, and apoptosis of osteoblast exposed to hydrogen peroxide
      (H(2)O(2)). Osteoblasts were treated with 1, 10, and 100 MUM of gamma-tocotrienol
      for 24 hours before being exposed to 490 MUM (IC(50)) H(2)O(2) for 2 hours.
      Results showed that gamma-tocotrienol prevented the malondialdehyde (MDA)
      elevation induced by H(2)O(2) in a dose-dependent manner. As for the antioxidant
      enzymes assays, all doses of gamma-tocotrienol were able to prevent the reduction
      in SOD and CAT activities, but only the dose of 1 MUM of GTT was able to prevent
      the reduction in GPx. As for the apoptosis assays, gamma-tocotrienol was able to
      reduce apoptosis at the dose of 1 and 10 MUM. However, the dose of 100 MUM of
      gamma-tocotrienol induced an even higher apoptosis than H(2)O(2). In conclusion,
      low doses of gamma-tocotrienol offered protection for osteoblasts against
      H(2)O(2) toxicity, but itself caused toxicity at the high doses.

PMID- 22956978
TI  - Protective Effects of Green Tea Extract against Hepatic Tissue Injury in
      Streptozotocin-Induced Diabetic Rats.
AB  - Although diabetic hepatopathy is potentially less common, it may be appropriate
      for addition to the list of target organ conditions related to diabetes. This
      study was designed to evaluate the hepatoprotective properties of green tea
      extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic
      through single injection of STZ (75 mg/kg i.p.). The rats were randomly divided
      into four groups of 10 animals each: Group 1, healthy control; Group 2,
      nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3,
      diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum
      biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and
      reduced glutathione (GSH) contents were measured to assess free radical activity
      in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase
      (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined.
      The biochemical findings were matched with histopathological verifications. Liver
      MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3
      significantly increased compared to Group 1 (P < 0.05) and significantly
      decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH,
      SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly
      decreased compared to Group 1 (P < 0.05) and were significantly increased in
      Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in
      the same direction with biochemical findings. This study proved the
      hepatoprotective activity of GTE in experimentally induced diabetic rats.

PMID- 22956979
TI  - Effects of Electroacupuncture at Head Points on the Function of Cerebral Motor
      Areas in Stroke Patients: A PET Study.
AB  - Positron emission tomography (PET) is used to observe the cerebral function
      widely and is a good method to explore the mechanism of acupuncture treatment on
      the central nervous system. By using this method, we observed the cerebral
      function of 6 patients suffering from ischemic stroke after receiving EA
      treatment at Baihui(GV20) and right Qubin(GB7). The results were: (1) the glucose
      metabolism changed significantly on primary motor area (M1), premotor cortex
      (PMC), and superior parietal louble (LPs) bilaterally, as well as the
      Supplementary Motor Area (SMA) on the unaffected hemisphere right after the first
      EA treatment. (2) The glucose metabolism on bilateral M1 and LPs changed
      significantly after three weeks of daily EA treatments. (3) The glucose
      metabolism on other areas such as insula, putamen, and cerebellum changed
      significantly. It demonstrated that EA at Qubin and Baihui couldactivate the
      cerebral structures related to motor function on the bilateral hemispheres.We
      concluded that EA was very helpful for the cerebral motor plasticity after the
      ischemic stroke. Also based on this study we assumed that the brain plasticity
      should be a network and that acupuncture participated in some sections of this
      course.

PMID- 22956980
TI  - Model systems for single molecule polymer dynamics.
AB  - Double stranded DNA (dsDNA) has long served as a model system for single molecule
      polymer dynamics. However, dsDNA is a semiflexible polymer, and the structural
      rigidity of the DNA double helix gives rise to local molecular properties and
      chain dynamics that differ from flexible chains, including synthetic organic
      polymers. Recently, we developed single stranded DNA (ssDNA) as a new model
      system for single molecule studies of flexible polymer chains. In this work, we
      discuss model polymer systems in the context of "ideal" and "real" chain behavior
      considering thermal blobs, tension blobs, hydrodynamic drag and force-extension
      relations. In addition, we present monomer aspect ratio as a key parameter
      describing chain conformation and dynamics, and we derive dynamical scaling
      relations in terms of this molecular-level parameter. We show that asymmetric
      Kuhn segments can suppress monomer-monomer interactions, thereby altering global
      chain dynamics. Finally, we discuss ssDNA in the context of a new model system
      for single molecule polymer dynamics. Overall, we anticipate that future single
      polymer studies of flexible chains will reveal new insight into the dynamic
      behavior of "real" polymers, which will highlight the importance of molecular
      individualism and the prevalence of non-linear phenomena.

PMID- 22956981
TI  - Direct observation of single flexible polymers using single stranded DNA().
AB  - Over the last 15 years, double stranded DNA (dsDNA) has been used as a model
      polymeric system for nearly all single polymer dynamics studies. However, dsDNA
      is a semiflexible polymer with markedly different molecular properties compared
      to flexible chains, including synthetic organic polymers. In this work, we report
      a new system for single polymer studies of flexible chains based on single
      stranded DNA (ssDNA). We developed a method to synthesize ssDNA for fluorescence
      microscopy based on rolling circle replication, which generates long strands (>65
      kb) of ssDNA containing "designer" sequences, thereby preventing intramolecular
      base pair interactions. Polymers are synthesized to contain amine-modified bases
      randomly distributed along the backbone, which enables uniform labelling of
      polymer chains with a fluorescent dye to facilitate fluorescence microscopy and
      imaging. Using this approach, we synthesized ssDNA chains with long contour
      lengths (>30 MUm) and relatively low dye loading ratios (~1 dye per 100 bases).
      In addition, we used epifluorescence microscopy to image single ssDNA polymer
      molecules stretching in flow in a microfluidic device. Overall, we anticipate
      that ssDNA will serve as a useful model system to probe the dynamics of polymeric
      materials at the molecular level.

PMID- 22956982
TI  - A study of non-invasive Patlak quantification for whole-body dynamic FDG-PET
      studies of mice.
AB  - Physiological changes in dynamic PET images can be quantitatively estimated by
      kinetic modeling technique. The process of PET quantification usually requires an
      input function in the form of a plasma-time activity curve (PTAC), which is
      generally obtained by invasive arterial blood sampling. However, invasive
      arterial blood sampling poses many challenges especially for small animal
      studies, due to the subjects' limited blood volume and small blood vessels. A
      simple non-invasive quantification method based on Patlak graphical analysis
      (PGA) has been recently proposed to use a reference region to derive the relative
      influx rate for a target region without invasive blood sampling, and evaluated by
      using the simulation data of human brain FDG-PET studies. In this study, the non
      invasive Patlak (nPGA) method was extended to whole-body dynamic small animal FDG
      PET studies. The performance of nPGA was systematically investigated by using
      experimental mouse studies and computer simulations. The mouse studies showed
      high linearity of relative influx rates between the nPGA and PGA for most pairs
      of reference and target regions, when an appropriate underlying kinetic model was
      used. The simulation results demonstrated that the accuracy of the nPGA method
      was comparable to that of the PGA method, with a higher reliability for most
      pairs of reference and target regions. The results proved that the nPGA method
      could provide a non-invasive and indirect way for quantifying the FDG kinetics of
      tumor in small animal studies.

PMID- 22956983
TI  - Robotic single-incision laparoscopic cholecystectomy.

PMID- 22956984
TI  - Influence of Transmural Pressure and Cytoskeletal Structure on NF-kappaB
      Activation in Respiratory Epithelial Cells.
AB  - Respiratory epithelial cells are exposed to complex mechanical forces which are
      often modulated during pathological conditions such as Otitis Media and acute
      lung injury. The transduction of these mechanical forces into altered
      inflammatory signaling may play an important role in the persistence of disease
      conditions and inflammation. In this study, we investigated how static and
      oscillatory pressures altered the activation of NF-kappaB inflammatory pathways
      and how changes in the actin cytoskeleton influenced the mechanotransduction of
      pressure into NF-kappaB activation. An in vitro system was used to apply static
      and oscillatory pressures to alveolar epithelial cells cultured at an air-liquid
      interface. Latrunculin A and Jasplakinolide were used to alter the cytoskeleton
      and tight-junction structure and ELISA was used to monitor activation of NF
      kappaB. Results indicate that both static and oscillatory pressures can activate
      NF-kappaB and that this activation is magnitude-dependent at low oscillation
      frequencies only. Jasplakinolide treated cells did not exhibit significant
      changes in normalized NF-kappaB activation compared to unloaded controls while
      Latrunculin treated cells exhibited increases in normalized NF-kappaB activation
      only at low frequency or static pressures. These results indicate that altering
      the actin cytoskeleton may be a useful way to mitigate the mechanotransduction of
      pressure forces into inflammatory signaling.

PMID- 22956986
TI  - The direction of masked auditory category priming correlates with participants'
      prime discrimination ability.
AB  - Semantic priming refers to the phenomenon that participants typically respond
      faster to targets following semantically related primes as compared to
      semantically unrelated primes. In contrast, Wentura and Frings (2005) found a
      negatively signed priming effect (i.e., faster responses to semantically
      unrelated as compared to semantically related targets) when they used (a) a
      special masking technique for the primes and (b) categorically related prime
      target-pairs (e.g., fruit-apple). The negatively signed priming effect was most
      pronounced for participants with random prime discrimination performance, whereas
      participants with high prime discrimination performance showed a positive effect.
      In the present study we analyzed the after-effects of masked category primes in
      audition. A comparable pattern of results as in the visual modality emerged: The
      poorer the individual prime discrimination, the more negative is the semantic
      priming effect. This result is interpreted as evidence for a common mechanism
      causing the semantic priming effect in vision as well as in audition instead of a
      perceptual mechanism only working in the visual domain.

PMID- 22956985
TI  - Deletion of the huntingtin proline-rich region does not significantly affect
      normal huntingtin function in mice.
AB  - The N-terminus of Huntingtin, the protein encoded by the Huntington's disease
      gene, contains a stretch of polyglutamine residues that is expanded in
      Huntington's disease. The polyglutamine stretch is flanked by two conserved
      protein domains in vertebrates: an N1-17 domain, and a proline-rich region (PRR).
      The PRR can modulate the structure of the adjacent polyglutamine stretch, and is
      a binding site for several interacting proteins. To determine the role of the PRR
      in Huntingtin function, we have generated a knock-in allele of the mouse
      Huntington's disease gene homolog that expresses full-length normal huntingtin
      lacking the PRR. Mice that are homozygous for the huntingtin PRR deletion are
      born at the normal Mendelian frequency, suggesting that the PRR is not required
      for essential huntingtin functions during embryonic development. Moreover, adult
      homozygous mutants did not exhibit any significant differences from wild-type
      controls in general motor function and motor learning. However, 18 month-old
      male, but not female, homozygous PRR deletion mutants exhibited deficits in the
      Morris water task, suggesting that age-dependent spatial learning and memory may
      be affected in a sex-specific fashion by the huntingtin PRR deletion. 

PMID- 22956987
TI  - The processing of inter-item relations as a moderating factor of retrieval
      induced forgetting.
AB  - We investigated influences of item generation and emotional valence on retrieval
      induced forgetting. Drawing on postulates of the three-factor theory of
      generation effects, generation tasks differentially affecting the processing of
      inter-item relations were applied. Whereas retrieval-induced forgetting of freely
      generated items was moderated by the emotional valence as well as retrieval
      induced forgetting of read items, even though in the reverse direction
      (Experiment 1), fragment completion eliminated the moderation of retrieval
      induced forgetting by emotional valence (Experiment 2). The results corroborate
      the assumption that the processing of inter-item relations is crucial for the
      immunization against retrieval-induced forgetting. Moreover, differential
      processing of inter-item relations may clarify the mixed results on moderating
      factors of retrieval-induced forgetting that have been reported.

PMID- 22956988
TI  - Memory for facial expression is influenced by the background music playing during
      study.
AB  - The effect of the emotional quality of study-phase background music on subsequent
      recall for happy and sad facial expressions was investigated. Undergraduates (N =
      48) viewed a series of line drawings depicting a happy or sad child in a variety
      of environments that were each accompanied by happy or sad music. Although memory
      for faces was very accurate, emotionally incongruent background music biased
      subsequent memory for facial expressions, increasing the likelihood that happy
      faces were recalled as sad when sad music was previously heard, and that sad
      faces were recalled as happy when happy music was previously heard. Overall, the
      results indicated that when recalling a scene, the emotional tone is set by an
      integration of stimulus features from several modalities.

PMID- 22956990
TI  - Can you eat it? A link between categorization difficulty and food likability.
AB  - In the present study we examined whether categorization difficulty regarding a
      food is related to its likability. For this purpose, we produced stimulus images
      by morphing photographs of a tomato and a strawberry. Subjects categorized these
      images as either a tomato or a strawberry and in separate sessions evaluated the
      food's eatability or the subject's willingness to eat (Experiments 1 and 2) and
      the likeliness of existence of each food (Experiment 2). The lowest score for ca-
      tegorization confidence coincided with the lowest scores for eatability,
      willingness to eat, and likeliness of existence. In Experiment 3, we found that
      food neophobia, a trait of ingestion avoidance of novel foods, modulated food
      likability but not categorization confidence. These findings suggest that a high
      categorization difficulty generally co-occurs with a decrease in food likability
      and that food neophobia modulates likability. This avoidance of difficult-to
      categorize foods seems ecologically valid because before eating we have little
      information regarding whether a food is potentially harmful.

PMID- 22956989
TI  - The very same thing: Extending the object token concept to incorporate causal
      constraints on individual identity.
AB  - The contributions of feature recognition, object categorization, and recollection
      of episodic memories to the re-identification of a perceived object as the very
      same thing encountered in a previous perceptual episode are well understood in
      terms of both cognitive-behavioral phenomenology and neurofunctional
      implementation. Human beings do not, however, rely solely on features and context
      to re-identify individuals; in the presence of featural change and similarly
      featured distractors, people routinely employ causal constraints to establish
      object identities. Based on available cognitive and neurofunctional data, the
      standard object-token based model of individual re-identification is extended to
      incorporate the construction of unobserved and hence fictive causal histories
      (FCHs) of observed objects by the pre-motor action planning system. It is
      suggested that functional deficits in the construction of FCHs are associated
      with clinical outcomes in both autism spectrum disorders and later-stage stage
      Alzheimer's disease.

PMID- 22956991
TI  - Emotional enhancement of immediate memory: Positive pictorial stimuli are better
      recognized than neutral or negative pictorial stimuli.
AB  - We examined emotional memory enhancement (EEM) for negative and positive pictures
      while manipulating encoding and retrieval conditions. Two groups of 40
      participants took part in this study. Both groups performed immediate implicit
      (categorization task) and explicit (recognition task) retrieval, but for one
      group the tasks were preceded by incidental encoding and for the other group by
      intentional encoding. As indicated by the sensitivity index (d'), after
      incidental encoding positive stimuli were easier to recognize than negative and
      neutral stimuli. Participants' response criterion was more liberal for negative
      stimuli than for both positive and neutral ones, independent of encoding
      condition. In the implicit retrieval task, participants were slower in
      categorizing positive than negative and neutral stimuli. However, the priming
      effect was larger for emotional than for neutral stimuli. These results are
      discussed in the context of the idea that the effect of emotion on immediate
      memory enhancement may depend on the intentionality to encode and retrieve
      information.

PMID- 22956993
TI  - Prevalence of pulmonary tuberculosis among adults in a rural sub-district of
      South India.
AB  - BACKGROUND: We conducted a survey to estimate point prevalence of
      bacteriologically positive pulmonary TB (PTB) in a rural area in South India,
      implementing TB program DOTS strategy since 2002. METHODS: Survey was conducted
      among persons >= 15 years of age in fifteen clusters selected by simple random
      sampling; each consisting of 5-12 villages. Persons having symptoms suggestive of
      PTB or history of anti-TB treatment (ATT) were eligible for sputum examination by
      smear microscopy for Acid Fast Bacilli and culture for Mycobacterium
      tuberculosis; two sputum samples were collected from each eligible person.
      Persons with one or both sputum specimen positive on microscopy and/or culture
      were labeled suffering from PTB. Prevalence was estimated after imputing missing
      values to correct for bias introduced by incompleteness of data. In six clusters,
      registered persons were also screened by X-ray chest. Persons with any abnormal
      shadow on X-ray were eligible for sputum examination in addition to those with
      symptoms and ATT. Multiplication factor calculated as ratio of prevalence while
      using both screening tools to prevalence using symptoms screening alone was
      applied to entire study population to estimate prevalence corrected for non
      screening by X-ray. RESULTS: Of 71,874 residents >= 15 years of age, 63,362
      (88.2%) were screened for symptoms and ATT. Of them, 5120 (8.1%) - 4681 (7.4%)
      with symptoms and an additional 439 (0.7%) with ATT were eligible for sputum
      examination. Spot specimen were collected from 4850 (94.7%) and early morning
      sputum specimens from 4719 (92.2%). Using symptom screening alone, prevalence of
      smear, culture and bacteriologically positive PTB in persons >= 15 years of age
      was 83 (CI: 57-109), 152 (CI: 108-197) and 196 (CI :145-246) per 100,000
      population respectively. Prevalence corrected for non-screening by X-ray was 108
      (CI: 82-134), 198 (CI: 153-243) and 254 (CI: 204-301) respectively. CONCLUSION:
      Observed prevalence suggests further strengthening of TB control program.

PMID- 22956992
TI  - Transcriptional abnormalities of hamstring muscle contractures in children with
      cerebral palsy.
AB  - Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum
      of movement disorders. Secondary to the neurological lesion, muscles from
      patients with CP are often spastic and form debilitating contractures that limit
      range of motion and joint function. With no genetic component, the pathology of
      skeletal muscle in CP is a response to aberrant complex neurological input in
      ways that are not fully understood. This study was designed to gain further
      understanding of the skeletal muscle response in CP using transcriptional
      profiling correlated with functional measures to broadly investigate muscle
      adaptations leading to mechanical deficits.Biopsies were obtained from both the
      gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10)
      and typically developing patients (n = 10) undergoing surgery. Biopsies were
      obtained to define the unique expression profile of the contractures and passive
      mechanical testing was conducted to determine stiffness values in previously
      published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data,
      which was validated for selected transcripts using quantitative real-time PCR.
      Chips were clustered based on their expression and those from patients with CP
      clustered separately. Significant genes were determined conservatively based on
      the overlap of three summarization algorithms (n = 1,398). Significantly altered
      genes were analyzed for over-representation among gene ontologies and muscle
      specific networks.The majority of altered transcripts were related to increased
      extracellular matrix expression in CP and a decrease in metabolism and ubiquitin
      ligase activity. The increase in extracellular matrix products was correlated
      with mechanical measures demonstrating the importance in disability. These data
      lay a framework for further studies and development of novel therapies.

PMID- 22956994
TI  - A novel approach for transcription factor analysis using SELEX with high
      throughput sequencing (TFAST).
AB  - BACKGROUND: In previous work, we designed a modified aptamer-free SELEX-seq
      protocol (afSELEX-seq) for the discovery of transcription factor binding sites.
      Here, we present original software, TFAST, designed to analyze afSELEX-seq data,
      validated against our previously generated afSELEX-seq dataset and a model
      dataset. TFAST is designed with a simple graphical interface (Java) so that it
      can be installed and executed without extensive expertise in bioinformatics.
      TFAST completes analysis within minutes on most personal computers. METHODOLOGY:
      Once afSELEX-seq data are aligned to a target genome, TFAST identifies peaks and,
      uniquely, compares peak characteristics between cycles. TFAST generates a
      hierarchical report of graded peaks, their associated genomic sequences, binding
      site length predictions, and dummy sequences. PRINCIPAL FINDINGS: Including
      additional cycles of afSELEX-seq improved TFAST's ability to selectively identify
      peaks, leading to 7,274, 4,255, and 2,628 peaks identified in two-, three-, and
      four-cycle afSELEX-seq. Inter-round analysis by TFAST identified 457 peaks as the
      strongest candidates for true binding sites. Separating peaks by TFAST into
      classes of worst, second-best and best candidate peaks revealed a trend of
      increasing significance (e-values 4.5 * 10(12), 2.9 * 10(-46), and 1.2 * 10(-73))
      and informational content (11.0, 11.9, and 12.5 bits over 15 bp) of discovered
      motifs within each respective class. TFAST also predicted a binding site length
      (28 bp) consistent with non-computational experimentally derived results for the
      transcription factor PapX (22 to 29 bp). CONCLUSIONS/SIGNIFICANCE: TFAST offers a
      novel and intuitive approach for determining DNA binding sites of proteins
      subjected to afSELEX-seq. Here, we demonstrate that TFAST, using afSELEX-seq
      data, rapidly and accurately predicted sequence length and motif for a putative
      transcription factor's binding site.

PMID- 22956995
TI  - Population structure of Bartonella henselae in Algerian urban stray cats.
AB  - Whole blood samples from 211 stray cats from Algiers, Algeria, were cultured to
      detect the presence of Bartonella species and to evaluate the genetic diversity
      of B. henselae strains by multiple locus VNTR analysis (MLVA). Bartonella
      henselae was the only species isolated from 36 (17%) of 211 cats. B. henselae
      genotype I was the predominant genotype (64%). MLVA typing of 259 strains from 30
      bacteremic cats revealed 52 different profiles as compared to only 3 profiles
      using MLST. Of these 52 profiles, 48 (92.3%) were identified for the first time.
      One-third of the cats harbored one MLVA profile only. As there was a correlation
      between the age of cats and the number of MLVA profiles, we hypothesized that the
      single profile in these cats was the profile of the initial infecting strain. Two
      third of the cats harbored 2 to 6 MLVA profiles simultaneously. The similarity of
      MLVA profiles obtained from the same cat, neighbor-joining clustering and
      structure-neighbor clustering indicate that such a diversity likely results from
      two different mechanisms occurring either independently or simultaneously:
      independent infections and genetic drift from a primary strain.

PMID- 22956996
TI  - The minimal deneddylase core of the COP9 signalosome excludes the Csn6 MPN-
      domain.
AB  - The COP9 signalosome (CSN) is a eukaryotic protein complex, which regulates a
      wide range of biological processes mainly through modulating the cullin ubiquitin
      E3 ligases in the ubiquitin-proteasome pathway. The CSN possesses a highly
      conserved deneddylase activity that centers at the JAMM motif of the Csn5 subunit
      but requires other subunits in a complex assembly. The classic CSN is composed of
      8 subunits (Csn1-8), yet in several Ascomycota, the complex is smaller and lacks
      orthologs for a few CSN subunits, but nevertheless contains a conserved Csn5.
      This feature makes yeast a powerful model to determine the minimal assemblage
      required for deneddylation activity. Here we report, that Csi1, a diverged S.
      cerevisiae CSN subunit, displays significant homology with the carboxyl terminal
      domain of the canonical Csn6, but lacks the amino terminal MPN(-) domain. Through
      the comparative and experimental analyses of the budding yeast and the mammalian
      CSNs, we demonstrate that the MPN(-) domain of the canonical mouse Csn6 is not
      part of the CSN deneddylase core. We also show that the carboxyl domain of Csn6
      has an indispensable role in maintaining the integrity of the CSN complex. The
      CSN complex assembled with the carboxyl fragment of Csn6, despite its lack of an
      MPN(-) domain, is fully active in deneddylation of cullins. We propose that the
      budding yeast Csi1 is a functional equivalent of the canonical Csn6, and thus the
      composition of the CSN across phyla is more conserved than hitherto appreciated.

PMID- 22956997
TI  - Lexical references to sensory modalities in verbal descriptions of people and
      objects by congenitally blind, late blind and sighted adults.
AB  - BACKGROUND: Some previous studies have revealed that while congenitally blind
      people have a tendency to refer to visual attributes ('verbalism'), references to
      auditory and tactile attributes are scarcer. However, this statement may be
      challenged by current theories claiming that cognition is linked to the
      perceptions and actions from which it derives. Verbal productions by the blind
      could therefore differ from those of the sighted because of their specific
      perceptual experience. The relative weight of each sense in oral descriptions was
      compared in three groups with different visual experience Congenitally blind
      (CB), late blind (LB) and blindfolded sighted (BS) adults. METHODOLOGY/PRINCIPAL
      FINDINGS: Participants were asked to give an oral description of their mother and
      their father, and of four familiar manually-explored objects. The number of
      visual references obtained when describing people was relatively high, and was
      the same in the CB and BS groups ("verbalism" in the CB). While references to
      touch were scarce in all groups, the CB referred to audition more frequently than
      the LB and the BS groups. There were, by contrast, no differences between groups
      in descriptions of objects, and references to touch dominated the other
      modalities. CONCLUSION/SIGNIFICANCE: The relative weight of each modality varies
      according to the cognitive processes involved in each task. Long term memory,
      internal representations and information acquired through social communication,
      are at work in the People task, seem to favour visual references in both the
      blind and the sighted, whereas the congenitally blind also refer often to
      audition. By contrast, the perceptual encoding and working memory at work in the
      Objects task enhance sensory references to touch in a similar way in all groups.
      These results attenuate the impact of verbalism in blindness, and support (albeit
      moderately) the idea that the perceptual experience of the congenitally blind is
      to some extent reflected in their cognition.

PMID- 22956998
TI  - Autocrine Sonic hedgehog attenuates inflammation in cerulein-induced acute
      pancreatitis in mice via upregulation of IL-10.
AB  - Hedgehog signaling plays critical roles in pancreatic oncogenesis and chronic
      pancreatitis, but its roles in acute pancreatitis (AP) are largely ambiguous. In
      this study, we provide evidence that Sonic hedgehog (Shh), but neither Desert
      hedgehog (Dhh) nor Indian hedgehog (Ihh), is the main protein whose expression is
      activated during the development of cerulein-induced acute pancreatitis in mice,
      and the Shh serves as an anti-inflammation factor in an autocrine manner.
      Blocking autocrine Shh signaling with anti-Shh neutralizing antibody aggravates
      the progression of acute pancreatitis. Mechanistic insight into Shh signaling
      activation in acute pancreatitis indicates that inflammatory stimulation
      activates Shh expression and secretion, and subsequently upregulates the
      expression and secretion of interleukin-10 (IL-10). Moreover, inhibition of Shh
      signaling with neutralizing antibody abolishes IL-10 production in vivo and in
      vitro. Molecular biological studies show that autocrine Shh signaling activates
      the key transcriptional factor Gli1 so that the target gene IL-10 is upregulated,
      leading to the protective and anti-inflammatory functions in the mouse model of
      acute pancreatitis. Thus, this study suggests autocrine Shh signaling functions
      as a protective signaling in the progression of acute pancreatitis.

PMID- 22956999
TI  - Complex structure of engineered modular domains defining molecular interaction
      between ICAM-1 and integrin LFA-1.
AB  - Intermolecular contacts between integrin LFA-1 (alpha(L)beta(2)) and ICAM-1
      derive solely from the integrin alpha(L) I domain and the first domain (D1) of
      ICAM-1. This study presents a crystal structure of the engineered complex of the
      alpha(L) I domain and ICAM-1 D1. Previously, we engineered the I domain for high
      affinity by point mutations that were identified by a directed evolution
      approach. In order to examine alpha(L) I domain allostery between the C-terminal
      alpha7-helix (allosteric site) and the metal-ion dependent adhesion site (active
      site), we have chosen a high affinity variant without mutations directly
      influencing either the position of the alpha7-helix or the active sites. In our
      crystal, the alpha(L) I domain was found to have a high affinity conformation to
      D1 with its alpha7-helix displaced downward away from the binding interface,
      recapitulating a current understanding of the allostery in the I domain and its
      linkage to neighboring domains of integrins in signaling. To enable soluble D1 of
      ICAM-1 to fold on its own, we also engineered D1 to be functional by mutations,
      which were found to be those that would convert hydrogen bond networks in the
      solvent-excluded core into vdW contacts. The backbone structure of the beta
      sandwich fold and the epitope for I domain binding of the engineered D1 were
      essentially identical to those of wild-type D1. Most deviations in engineered D1
      were found in the loops at the N-terminal region that interacts with human
      rhinovirus (HRV). Structural deviation found in engineered D1 was overall in
      agreement with the function of engineered D1 observed previously, i.e., full
      capacity binding to alpha(L) I domain but reduced interaction with HRV.

PMID- 22957000
TI  - Human immunodeficiency virus type-1 (HIV-1) continues to evolve in presence of
      broadly neutralizing antibodies more than ten years after infection.
AB  - BACKGROUND: The evolution of HIV-1 and its immune escape to autologous
      neutralizing antibodies (Nabs) during the acute/early phases of infection have
      been analyzed in depth in many studies. In contrast, little is known about
      neither the long-term evolution of the virus in patients who developed broadly
      Nabs (bNabs) or the mechanism of escape in presence of these bNabs. RESULTS: We
      have studied the viral population infecting a long term non progressor HIV-1
      infected patient who had developed broadly neutralizing antibodies toward all
      tier 2/3 viruses (6 clades) tested, 9 years after infection, and was then
      followed up over 7 years. The autologous neutralization titers of the sequential
      sera toward env variants representative of the viral population significantly
      increased during the follow-up period. The most resistant pseudotyped virus was
      identified at the last visit suggesting that it represented a late emerging
      escape variant. We identified 5 amino acids substitutions that appeared
      associated with escape to broadly neutralizing antibodies. They were V319I/S,
      R/K355T, R/W429G, Q460E and G/T463E, in V3, C3 and V5 regions. CONCLUSION: This
      study showed that HIV-1 may continue to evolve in presence of both broadly
      neutralizing antibodies and increasing autologous neutralizing activity more than
      10 years post-infection.

PMID- 22957001
TI  - Response of high-sensitive C-reactive protein to catheter ablation of atrial
      fibrillation and its relation with rhythm outcome.
AB  - AIMS: This study investigated the possible association between hs-CRP as well as
      hs-CRP changes and rhythm outcome after AF catheter ablation. METHODS: We studied
      68 consecutive patients with AF undergoing catheter ablation. hs-CRP levels were
      measured using commercially available assays before and 6 months after catheter
      ablation. Serial 7-day Holter ECGs were used to detect AF recurrences. RESULTS:
      Early AF recurrence (ERAF, within one week) was observed in 38%, while late AF
      recurrence (LRAF, between 3 and 6 months) occurred in 18% of the patients. None
      of the baseline clinical or echocardiographic variables was predictive of ERAF or
      LRAF. Baseline hs-CRP measured 2.07 +/- 1.1 ug/ml and was not associated with
      ERAF and LRAF. At 6 months, hs-CRP levels were comparable with baseline values
      (2.14+/-1.19 ug/ml, p = 0.409) and were also not related with LRAF. However,
      patients with LRAF showed an hs-CRP increase from 2.03 +/- 0.61 to 2.62 +/- 1.52
      ug/ml (p = 0.028). Patients with an hs-CRP change in the upper tertile (>0.2
      ug/ml) had LRAF in 32% as opposed to 11% (p = 0.042) in patients in the lower (<
      0.3 ug/ml) or intermediate (-0.3-0.2 ug/ml) tertile. CONCLUSIONS: Changes in hs
      CRP but not baseline hs-CRP are associated with rhythm outcome after AF catheter
      ablation. This finding points to a link between an inflammatory response and AF
      recurrence in this setting.

PMID- 22957002
TI  - Metabolite profiling of a diverse collection of wheat lines using
      ultraperformance liquid chromatography coupled with time-of-flight mass
      spectrometry.
AB  - Genetic differences among major types of wheat are well characterized; however,
      little is known about how these distinctions affect the small molecule profile of
      the wheat seed. Ethanol/water (65% v/v) extracts of seed from 45 wheat lines
      representing 3 genetically distinct classes, tetraploid durum (Triticum turgidum
      subspecies durum) (DW) and hexaploid hard and soft bread wheat (T. aestivum
      subspecies aestivum) (BW) were subjected to ultraperformance liquid
      chromatography coupled with time-of-flight mass spectrometry (UPLC-TOF-MS).
      Discriminant analyses distinguished DW from BW with 100% accuracy due to
      differences in expression of nonpolar and polar ions, with differences attributed
      to sterol lipids/fatty acids and phospholipids/glycerolipids, respectively. Hard
      versus soft BW was distinguished with 100% accuracy by polar ions, with
      differences attributed to heterocyclic amines and polyketides versus phospholipid
      ions, respectively. This work provides a foundation for identification of
      metabolite profiles associated with desirable agronomic and human health traits
      and for assessing how environmental factors impact these characteristics.

PMID- 22957003
TI  - High resolution melting analysis is a more sensitive and effective alternative to
      gel-based platforms in analysis of SSR--an example in citrus.
AB  - High resolution melting curve analysis (HRM) has been used as an efficient,
      accurate and cost-effective tool to detect single nucleotide polymorphisms (SNPs)
      or insertions or deletions (INDELs). However, its efficiency, accuracy and
      applicability to discriminate microsatellite polymorphism have not been
      extensively assessed. The traditional protocols used for SSR genotyping include
      PCR amplification of the DNA fragment and the separation of the fragments on
      electrophoresis-based platform. However, post-PCR handling processes are
      laborious and costly. Furthermore, SNPs present in the sequences flanking repeat
      motif cannot be detected by polyacrylamide-gel-electrophoresis based methods. In
      the present study, we compared the discriminating power of HRM with the
      traditional electrophoresis-based methods and provided a panel of primers for HRM
      genotyping in Citrus. The results showed that sixteen SSR markers produced
      distinct polymorphic melting curves among the Citrus spp investigated through HRM
      analysis. Among those, 10 showed more genotypes by HRM analysis than capillary
      electrophoresis owing to the presence of SNPs in the amplicons. For the SSR
      markers without SNPs present in the flanking region, HRM also gave distinct
      melting curves which detected same genotypes as were shown in capillary
      electrophoresis (CE) analysis. Moreover, HRM analysis allowed the discrimination
      of most of the 15 citrus genotypes and the resulting genetic distance analysis
      clustered them into three main branches. In conclusion, it has been approved that
      HRM is not only an efficient and cost-effective alternative of electrophoresis
      based method for SSR markers, but also a method to uncover more polymorphisms
      contributed by SNPs present in SSRs. It was therefore suggested that the panel of
      SSR markers could be used in a variety of applications in the citrus biodiversity
      and breeding programs using HRM analysis. Furthermore, we speculate that the HRM
      analysis can be employed to analyse SSR markers in a wide range of applications
      in all other species.

PMID- 22957004
TI  - Relationship between bone mineral density and serum osteoprotegerin in patients
      with chronic heart failure.
AB  - PURPOSE: Heart failure (HF) had been reported with increased risk of hip
      fractures. However, the relationship between circulating biomarkers and bone
      mineral density (BMD) in chronic HF remained unclear. METHODS: This is a cross
      sectional study which recruited stable chronic HF from registry of the Heart
      Failure Center of National Taiwan University Hospital. Patients underwent dual
      energy x-ray absorptiometry (DEXA) measurements at hip and lumbar spines and
      biochemical assessments including B-type natriuretic peptide (BNP-32), myostatin,
      follistatin and osteoprotegerin (OPG). RESULTS: A total of 115 stable chronic HF
      individuals with left ventricular ejection fraction (EF) <45% (74% of male, mean
      age at 59) were recruited with 24 patients in NYHA class I, 73 patients in NYHA
      class II and 18 patients in NYHA class III. Results of BMD showed that Z scores
      of hip in NYHA III group (-0.12 +/- 1.15) was significantly lower than who were
      NYHA II (0.58 +/- 1.04). Serum OPG was significantly higher in subjects of NYHA
      III (9.3 +/- 4.6 pmol/l) than NYHA II (7.4 +/- 2.8 pmol/l) or NYHA I (6.8 +/- 3.6
      pmol/l) groups. There's a significant negative association between log
      transformed serum OPG and trochanteric BMD (R = -0.299, P = 0.001), which
      remained significant after multivariate analysis. CONCLUSIONS: Our study
      demonstrated an inverse association between serum OPG and trochanteric BMD in
      patients with HF. OPG may be a predictor of BMD and an alternative to DEXA for
      identifying at risk HF patients for osteoporosis.

PMID- 22957005
TI  - Antidepressant treatment normalizes white matter volume in patients with major
      depression.
AB  - OBJECTIVE: To investigate white matter volume abnormalities in patients with
      major depression and the effects of antidepressant treatment on white matter
      volume. METHOD: Magnetic resonance imaging (MRI) was performed on 32 treatment
      naive depressed patients, 17 recovered patients who had received antidepressant
      treatment and subsequently achieved clinical recovery and 34 matched controls.
      RESULTS: Relative to the healthy controls, the treatment-naive depressed patients
      showed increased white matter volumes in the left dorsolateral prefrontal cortex
      (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum
      posterior lobe and left inferior parietal lobule. For the treatment-naive
      patients, the length in months of the current depressive episode was positively
      correlated with the white matter volumes in both the left DLPFC and left putamen.
      In the recovered patients, the differences in white matter volume were no longer
      statistically significant relative to healthy controls. No significant difference
      was found in the total white matter volume among the three groups. CONCLUSIONS:
      This study demonstrates that there were alterations in the white matter volumes
      of depressed patients, which might disrupt the neural circuits that are involved
      in emotional and cognitive function and thus contribute to the pathophysiology of
      depression. The finding of the significant correlations between refractoriness
      and the white matter volumes in the left DLPFC and left putamen combined with the
      finding that antidepressant treatment normalized the white matter volume of
      recovered patients, suggests that a quantitative, structural MRI measurement
      could act as a potential biomarker in depression therapy for individual subjects.

PMID- 22957006
TI  - The potential of aspen clonal forestry in Alberta: breeding regions and estimates
      of genetic gain from selection.
AB  - BACKGROUND: Aspen naturally grows in large, single-species, even-aged stands that
      regenerate clonally after fire disturbance. This offers an opportunity for an
      intensive clonal forestry system that closely emulates the natural life history
      of the species. In this paper, we assess the potential of genetic tree
      improvement and clonal deployment to enhance the productivity of aspen forests in
      Alberta. We further investigate geographic patterns of genetic variation in aspen
      and infer forest management strategies under uncertain future climates.
      METHODOLOGY/PRINCIPAL FINDINGS: Genetic variation among 242 clones from Alberta
      was evaluated in 13 common garden trials after 5-8 growing seasons in the field.
      Broad-sense heritabilities for height and diameter at breast height (DBH) ranged
      from 0.36 to 0.64, allowing 5-15% genetic gains in height and 9-34% genetic gains
      in DBH. Geographic partitioning of genetic variance revealed predominant
      latitudinal genetic differentiation. We further observed that northward movement
      of clones almost always resulted in increased growth relative to local planting
      material, while southward movement had a strong opposite effect.
      CONCLUSION/SIGNIFICANCE: Aspen forests are an important natural resource in
      western Canada that is used for pulp and oriented strandboard production,
      accounting for ~40% of the total forest harvest. Moderate to high broad-sense
      heritabilities in growth traits suggest good potential for a genetic tree
      improvement program with aspen. Significant productivity gains appear possible
      through clonal selection from existing trials. We propose two breeding regions
      for Alberta, and suggest that well-tested southern clones may be used in the
      northern breeding region, accounting for a general warming trend observed over
      the last several decades in Alberta.

PMID- 22957007
TI  - The combined effect of individual and neighborhood socioeconomic status on cancer
      survival rates.
AB  - BACKGROUND: This population-based study investigated the relationship between
      individual and neighborhood socioeconomic status (SES) and mortality rates for
      major cancers in Taiwan. METHODS: A population-based follow-up study was
      conducted with 20,488 cancer patients diagnosed in 2002. Each patient was traced
      to death or for 5 years. The individual income-related insurance payment amount
      was used as a proxy measure of individual SES for patients. Neighborhood SES was
      defined by income, and neighborhoods were grouped as living in advantaged or
      disadvantaged areas. The Cox proportional hazards model was used to compare the
      death-free survival rates between the different SES groups after adjusting for
      possible confounding and risk factors. RESULTS: After adjusting for patient
      characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and
      area of residence), tumor extent, treatment modalities (operation and adjuvant
      therapy), and hospital characteristics (ownership and teaching level), colorectal
      cancer, and head and neck cancer patients under 65 years old with low individual
      SES in disadvantaged neighborhoods conferred a 1.5 to 2-fold higher risk of
      mortality, compared with patients with high individual SES in advantaged
      neighborhoods. A cross-level interaction effect was found in lung cancer and
      breast cancer. Lung cancer and breast cancer patients less than 65 years old with
      low SES in advantaged neighborhoods carried the highest risk of mortality.
      Prostate cancer patients aged 65 and above with low SES in disadvantaged
      neighborhoods incurred the highest risk of mortality. There was no association
      between SES and mortality for cervical cancer and pancreatic cancer. CONCLUSIONS:
      Our findings indicate that cancer patients with low individual SES have the
      highest risk of mortality even under a universal health-care system. Public
      health strategies and welfare policies must continue to focus on this vulnerable
      group.

PMID- 22957008
TI  - New insights in gut microbiota establishment in healthy breast fed neonates.
AB  - The establishment of a pioneer gut microbiota is increasingly recognized as a
      crucial stage in neonatal development influencing health throughout life. While
      current knowledge is mainly based on either culture or molecular analysis of
      feces, we opted for a comprehensive approach complementing culture with state-of
      the-art molecular methods. The bacterial composition in feces from seven healthy
      vaginally-delivered, breast-fed neonates was analyzed at days 4-6, 9-14 and 25-30
      postnatal, using culture, 16S rRNA gene sequencing of isolates, quantitative PCR
      and pyrosequencing. Anaerobes outnumbered facultative anaerobes in all seven
      neonates within the first days of life, owing to high levels of Bifidobacterium
      and unexpectedly also Bacteroides, which were inversely correlated. Four neonates
      harbored maternal Bacteroides levels, comprising typical adult species,
      throughout the neonatal period, while in three only subdominant levels were
      detected. In contrast, the major adult-type butyrate-producing anaerobic
      populations, Roseburia and Faecalibacterium, remained undetectable during the
      neonatal period. The presence of Bacteroidetes as pioneer bacteria in the
      majority of neonates studied demonstrates that adult-type strict anaerobes may
      reach adult-like population densities within the first week of life. Consequently
      the switch from facultative to strict anaerobes may occur earlier than previously
      assumed in breast-fed neonates, and the establishment of the major butyrate
      producing populations may be limited by other factors than the absence of
      anaerobic conditions. The impact of breast milk components on the timing of
      establishment of anaerobic pioneer bacteria, as well as opportunistic pathogens
      should be further studied in regard to priming of the gut-associated immune
      system and consequences on later health.

PMID- 22957010
TI  - Properties of doublecortin expressing neurons in the adult mouse dentate gyrus.
AB  - The dentate gyrus is a neurogenic zone where neurons continue to be born
      throughout life, mature and integrate into the local circuitry. In adults, this
      generation of new neurons is thought to contribute to learning and memory
      formation. As newborn neurons mature, they undergo a developmental sequence in
      which different stages of development are marked by expression of different
      proteins. Doublecortin (DCX) is an early marker that is expressed in immature
      granule cells that are beginning migration and dendritic growth but is turned off
      before neurons reach maturity. In the present study, we use a mouse strain in
      which enhanced green fluorescent protein (EGFP) is expressed under the control of
      the DCX promoter. We show that these neurons have high input resistances and some
      cells can discharge trains of action potentials. In mature granule cells, action
      potentials are followed by a slow afterhyperpolarization that is absent in EGFP
      positive neurons. EGFP-positive neurons had a lower spine density than mature
      neurons and stimulation of either the medial or lateral perforant pathway
      activated dual component glutamatergic synapses that had both AMPA and NMDA
      receptors. NMDA receptors present at these synapses had slow kinetics and were
      blocked by ifenprodil, indicative of high GluN2B subunit content. These results
      show that EGFP-positive neurons in the DCX-EGFP mice are functionally immature
      both in their firing properties and excitatory synapses.

PMID- 22957009
TI  - Phenotypic characterization of prostate cancer LNCaP cells cultured within a
      bioengineered microenvironment.
AB  - Biophysical and biochemical properties of the microenvironment regulate cellular
      responses such as growth, differentiation, morphogenesis and migration in normal
      and cancer cells. Since two-dimensional (2D) cultures lack the essential
      characteristics of the native cellular microenvironment, three-dimensional (3D)
      cultures have been developed to better mimic the natural extracellular matrix. To
      date, 3D culture systems have relied mostly on collagen and MatrigelTM hydrogels,
      allowing only limited control over matrix stiffness, proteolytic degradability,
      and ligand density. In contrast, bioengineered hydrogels allow us to
      independently tune and systematically investigate the influence of these
      parameters on cell growth and differentiation. In this study, polyethylene glycol
      (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD)
      motifs, common cell-binding motifs in extracellular matrix proteins, and matrix
      metalloproteinase (MMP) cleavage sites, were characterized regarding their
      stiffness, diffusive properties, and ability to support growth of androgen
      dependent LNCaP prostate cancer cells. We found that the mechanical properties
      modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture
      periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like
      structures in 3D culture, with hypoxic and apoptotic cores. We further compared
      protein and gene expression levels between 3D and 2D cultures upon stimulation
      with the synthetic androgen R1881. Interestingly, the kinetics of R1881
      stimulated androgen receptor (AR) nuclear translocation differed between 2D and
      3D cultures when observed by immunofluorescent staining. Furthermore, microarray
      studies revealed that changes in expression levels of androgen responsive genes
      upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together,
      culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the
      cellular responses to androgen stimulation between the 2D and 3D environments.
      Therefore, we suggest that the presented 3D culture system represents a powerful
      tool for high throughput prostate cancer drug testing that recapitulates tumor
      microenvironment.

PMID- 22957011
TI  - Arbuscular mycorrhizal fungi promote the growth of Ceratocarpus arenarius
      (Chenopodiaceae) with no enhancement of phosphorus nutrition.
AB  - The mycorrhizal status of plants in the Chenopodiaceae is not well studied with a
      few controversial reports. This study examined arbuscular mycorrhizal (AM)
      colonization and growth response of Ceratocarpus arenarius in the field and a
      greenhouse inoculation trial. The colonization rate of AM fungi in C. arenarius
      in in-growth field cores was low (around 15%). Vesicles and intraradical hyphae
      were present during all growth stages, but no arbuscules were observed.
      Sequencing analysis of the large ribosomal rDNA subunit detected four culturable
      Glomus species, G. intraradices, G. mosseae, G. etunicatum and G. microaggregatum
      together with eight unculturable species belong to the Glomeromycota in the root
      system of C. arenarius collected from the field. These results establish the
      mycotrophic status of C. arenarius. Both in the field and in the greenhouse
      inoculation trial, the growth of C. arenarius was stimulated by the indigenous AM
      fungal community and the inoculated AM fungal isolates, respectively, but the P
      uptake and concentration of the mycorrhizal plants did not increase significantly
      over the controls in both experiments. Furthermore, the AM fungi significantly
      increased seed production. Our results suggest that an alternative reciprocal
      benefit to carbon-phosphorus trade-off between AM fungi and the chenopod plant
      might exist in the extremely arid environment.

PMID- 22957012
TI  - Universal access to HIV treatment versus universal 'test and treat':
      transmission, drug resistance & treatment costs.
AB  - In South Africa (SA) universal access to treatment for HIV-infected individuals
      in need has yet to be achieved. Currently ~1 million receive treatment, but an
      additional 1.6 million are in need. It is being debated whether to use a
      universal 'test and treat' (T&T) strategy to try to eliminate HIV in SA;
      treatment reduces infectivity and hence transmission. Under a T&T strategy all
      HIV-infected individuals would receive treatment whether in need or not. This
      would require treating 5 million individuals almost immediately and providing
      treatment for several decades. We use a validated mathematical model to predict
      impact and costs of: (i) a universal T&T strategy and (ii) achieving universal
      access to treatment. Using modeling the WHO has predicted a universal T&T
      strategy in SA would eliminate HIV within a decade, and (after 40 years) cost
      ~$10 billion less than achieving universal access. In contrast, we predict a
      universal T&T strategy in SA could eliminate HIV, but take 40 years and cost ~$12
      billion more than achieving universal access. We determine the difference in
      predictions is because the WHO has under-estimated survival time on treatment and
      ignored the risk of resistance. We predict, after 20 years, ~2 million
      individuals would need second-line regimens if a universal T&T strategy is
      implemented versus ~1.5 million if universal access is achieved. Costs need to be
      realistically estimated and multiple evaluation criteria used to compare
      'treatment as prevention' with other prevention strategies. Before implementing a
      universal T&T strategy, which may not be sustainable, we recommend striving to
      achieve universal access to treatment as quickly as possible. We predict
      achieving universal access to treatment would be a very effective 'treatment as
      prevention' approach and bring the HIV epidemic in SA close to elimination,
      preventing ~4 million infections after 20 years and ~11 million after 40 years.

PMID- 22957014
TI  - Flying at no mechanical energy cost: disclosing the secret of wandering
      albatrosses.
AB  - Albatrosses do something that no other birds are able to do: fly thousands of
      kilometres at no mechanical cost. This is possible because they use dynamic
      soaring, a flight mode that enables them to gain the energy required for flying
      from wind. Until now, the physical mechanisms of the energy gain in terms of the
      energy transfer from the wind to the bird were mostly unknown. Here we show that
      the energy gain is achieved by a dynamic flight manoeuvre consisting of a
      continually repeated up-down curve with optimal adjustment to the wind. We
      determined the energy obtained from the wind by analysing the measured
      trajectories of free flying birds using a new GPS-signal tracking method yielding
      a high precision. Our results reveal an evolutionary adaptation to an extreme
      environment, and may support recent biologically inspired research on robotic
      aircraft that might utilize albatrosses' flight technique for engineless
      propulsion.

PMID- 22957013
TI  - Short-term erythropoietin treatment does not substantially modulate monocyte
      transcriptomes of patients with combined heart and renal failure.
AB  - BACKGROUND: Combined heart and renal failure is associated with high
      cardiovascular morbidity and mortality. Anti-oxidant and anti-inflammatory, non
      hematopoietic effects of erythropoietin (EPO) treatment have been proposed.
      Monocytes may act as biosensors of the systemic environment. We hypothesized that
      monocyte transcriptomes of patients with cardiorenal syndrome (CRS) reflect the
      pathophysiology of the CRS and respond to short-term EPO treatment at a
      recommended dose for treatment of renal anemia. METHODS: Patients with CRS and
      anemia (n = 18) included in the EPOCARES trial were matched to healthy controls
      (n = 12). Patients were randomized to receive 50 IU/kg/week EPO or not. RNA from
      CD14(+)-monocytes was subjected to genome wide expression analysis (Illumina) at
      baseline and 18 days (3 EPO injections) after enrolment. Transcriptomes from
      patients were compared to healthy controls and effect of EPO treatment was
      evaluated within patients. RESULTS: In CRS patients, expression of 471 genes,
      including inflammation and oxidative stress related genes was different from
      healthy controls. Cluster analysis did not separate patients from healthy
      controls. The 6 patients with the highest hsCRP levels had more differentially
      expressed genes than the 6 patients with the lowest hsCRP levels. Analysis of the
      variation in log(2) ratios of all individual 18 patients indicated that 4 of the
      18 patients were different from the controls, whereas the other 14 were quite
      similar. After short-term EPO treatment, every patient clustered to his or her
      own baseline transcriptome. Two week EPO administration only marginally affected
      expression profiles on average, however, individual gene responses were variable.
      CONCLUSIONS: In stable, treated CRS patients with mild anemia, monocyte
      transcriptomes were modestly altered, and indicated imprints of inflammation and
      oxidative stress. EPO treatment with a fixed dose has hematopoietic effects, had
      no appreciable beneficial actions on monocyte transcription profiles, however,
      could also not be associated with undesirable transcriptional responses.

PMID- 22957015
TI  - Estimation of the burden of pandemic(H1N1)2009 in developing countries:
      experience from a tertiary care center in South India.
AB  - BACKGROUND: The burden of the pandemic (H1N1) 2009 influenza might be
      underestimated if detection of the virus is mandated to diagnose infection. Using
      an alternate approach, we propose that a much higher pandemic burden was
      experienced in our institution. METHODOLOGY/PRINCIPAL FINDINGS: Consecutive
      patients (n = 2588) presenting to our hospital with influenza like illness (ILI)
      or severe acute respiratory infection (SARI) during a 1-year period (May 2009
      April 2010) were prospectively recruited and tested for influenza A by real-time
      RT-PCR. Analysis of weekly trends showed an 11-fold increase in patients
      presenting with ILI/SARI during the peak pandemic period when compared with the
      pre-pandemic period and a significant (P<0.001) increase in SARI admissions
      during the pandemic period (30 +/- 15.9 admissions/week) when compared with pre
      pandemic (7 +/- 2.5) and post-pandemic periods (5 +/- 3.8). However, Influenza A
      was detected in less than one-third of patients with ILI/SARI [699 (27.0%)]; a
      majority of these (557/699, 79.7%) were Pandemic (H1N1)2009 virus [A/H1N1/09]. An
      A/H1N1/09 positive test was correlated with shorter symptom duration prior to
      presentation (p = 0.03). More ILI cases tested positive for A/H1N1/09 when
      compared with SARI (27.4% vs. 14.6%, P = 0.037). When the entire study population
      was considered, A/H1N1/09 positivity was associated with lower risk of
      hospitalization (p<0.0001) and ICU admission (p = 0.013) suggesting mild self
      limiting illness in a majority. CONCLUSION/SIGNIFICANCE: Analysis of weekly
      trends of ILI/SARI suggest a higher burden of the pandemic attributable to
      A/H1N1/09 than estimates assessed by a positive PCR test alone. The study
      highlights methodological consideration in the estimation of burden of pandemic
      influenza in developing countries using hospital-based data that may help assess
      the impact of future outbreaks of respiratory illnesses.

PMID- 22957016
TI  - Does cosleeping contribute to lower testosterone levels in fathers? Evidence from
      the Philippines.
AB  - Because cross-species evidence suggests that high testosterone (T) may interfere
      with paternal investment, the relationships between men's transition to parenting
      and changes in their T are of growing interest. Studies of human males suggest
      that fathers who provide childcare often have lower T than uninvolved fathers,
      but no studies to date have evaluated how nighttime sleep proximity between
      fathers and their offspring may affect T. Using data collected in 2005 and 2009
      from a sample of men (n = 362; age 26.0 +/- 0.3 years in 2009) residing in
      metropolitan Cebu, Philippines, we evaluated fathers' T based on whether they
      slept on the same surface as their children (same surface cosleepers), slept on a
      different surface but in the same room (roomsharers), or slept separately from
      their children (solitary sleepers). A large majority (92%) of fathers in this
      sample reported practicing same surface cosleeping. Compared to fathers who slept
      solitarily, same surface cosleeping fathers had significantly lower evening (PM)
      T and also showed a greater diurnal decline in T from waking to evening (both
      p<0.05). Among men who were not fathers at baseline (2005), fathers who were
      cosleepers at follow-up (2009) experienced a significantly greater longitudinal
      decline in PM T over the 4.5-year study period (p<0.01) compared to solitary
      sleeping fathers. Among these same men, baseline T did not predict fathers'
      sleeping arrangements at follow-up (p>0.2). These results are consistent with
      previous findings indicating that daytime father-child interaction contributes to
      lower T among fathers. Our findings specifically suggest that close sleep
      proximity between fathers and their offspring results in greater longitudinal
      decreases in T as men transition to fatherhood and lower PM T overall compared to
      solitary sleeping fathers.

PMID- 22957017
TI  - Trichosanthin inhibits breast cancer cell proliferation in both cell lines and
      nude mice by promotion of apoptosis.
AB  - Breast cancer ranks as a common and severe neoplasia in women with increasing
      incidence as well as high risk of metastasis and relapse. Translational and
      laboratory-based clinical investigations of new/novel drugs are in progress.
      Medicinal plants are rich sources of biologically active natural products for
      drug development. The 27-kDa trichosanthin (TCS) is a ribosome inactivating
      protein purified from tubers of the Chinese herbal plant Trichosanthes kirilowii
      Maximowicz (common name Tian Hua Fen). In this study, we extended the potential
      medicinal applications of TCS from HIV, ferticide, hydatidiform moles, invasive
      moles, to breast cancer. We found that TCS manifested anti-proliferative and
      apoptosis-inducing activities in both estrogen-dependent human MCF-7 cells and
      estrogen-independent MDA-MB-231 cells. Flow cytometric analysis disclosed that
      TCS induced cell cycle arrest. Further studies revealed that TCS-induced tumor
      cell apoptosis was attributed to activation of both caspase-8 and caspase-9
      regulated pathways. The subsequent events including caspase-3 activation, and
      increased PARP cleavage. With regard to cell morphology, stereotypical apoptotic
      features were observed. Moreover, in comparison with control, TCS- treated nude
      mice bearing MDA-MB-231 xenograft tumors exhibited significantly reduced tumor
      volume and tumor weight, due to the potent effect of TCS on tumor cell apoptosis
      as determined by the increase of caspase-3 activation, PARP cleavage, and DNA
      fragmentation using immunohistochemistry. Considering the clinical efficacy and
      relative safety of TCS on other human diseases, this work opens up new
      therapeutic avenues for patients with estrogen-dependent and/or estrogen
      independent breast cancers.

PMID- 22957018
TI  - Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using
      Raman microspectroscopy.
AB  - This paper presents a nonivasive approach to study redox state of reduced
      cytochromes c, c1 and b of complexes II and III in mitochondria of live
      cardiomyocytes by means of Raman microspectroscopy. For the first time with the
      proposed approach we perform studies of rod- and round-shaped cardiomyocytes,
      representing different morphological and functional states. Raman mapping and
      cluster analysis reveal that these cardiomyocytes differ in the amounts of
      reduced cytochromes c, c1 and b. The rod-shaped cardiomyocytes possess uneven
      distribution of reduced cytochromes c, c1 and b in cell center and periphery.
      Moreover, by means of Raman spectroscopy we demonstrated the decrease in the
      relative amounts of reduced cytochromes c, c1 and b in the rod-shaped
      cardiomyocytes caused by H2O2-induced oxidative stress before any visible
      changes. Results of Raman mapping and time-dependent study of reduced cytochromes
      of complexes II and III and cytochrome c in cardiomyocytes are in a good
      agreement with our fluorescence indicator studies and other published data.

PMID- 22957019
TI  - Approach-bias predicts development of cannabis problem severity in heavy cannabis
      users: results from a prospective FMRI study.
AB  - A potentially powerful predictor for the course of drug (ab)use is the approach
      bias, that is, the pre-reflective tendency to approach rather than avoid drug
      related stimuli. Here we investigated the neural underpinnings of cannabis
      approach and avoidance tendencies. By elucidating the predictive power of neural
      approach-bias activations for future cannabis use and problem severity, we aimed
      at identifying new intervention targets. Using functional Magnetic Resonance
      Imaging (fMRI), neural approach-bias activations were measured with a Stimulus
      Response Compatibility task (SRC) and compared between 33 heavy cannabis users
      and 36 matched controls. In addition, associations were examined between approach
      bias activations and cannabis use and problem severity at baseline and at six
      month follow-up. Approach-bias activations did not differ between heavy cannabis
      users and controls. However, within the group of heavy cannabis users, a positive
      relation was observed between total lifetime cannabis use and approach-bias
      activations in various fronto-limbic areas. Moreover, approach-bias activations
      in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)
      independently predicted cannabis problem severity after six months over and
      beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity
      during cannabis approach trials, but lower activity during cannabis avoidance
      trials were associated with decreases in cannabis problem severity. These
      findings suggest that cannabis users with deficient control over cannabis action
      tendencies are more likely to develop cannabis related problems. Moreover, the
      balance between cannabis approach and avoidance responses in the DLPFC and ACC
      may help identify individuals at-risk for cannabis use disorders and may be new
      targets for prevention and treatment.

PMID- 22957020
TI  - An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer
      drugs.
AB  - The epidermal growth factor receptor (EGFR) is a well-established target for
      cancer treatment. EGFR tyrosine kinase (TK) inhibitors, such as gefinitib and
      erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung
      carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and
      erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to
      these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling
      pathway have been studied extensively to provide insight into regulatory
      mechanisms conserved from C. elegans to humans. To develop an in vivo screening
      system for potential cancer drugs targeting specific EGFR mutants, we expressed
      three LET-23 chimeras in which the TK domain was replaced with either the human
      wild-type TK domain (LET-23::hEGFR-TK), a TK domain with the L858R mutation (LET
      23::hEGFR-TK[L858R]), or a TK domain with the T790M-L858R mutations (LET
      23::hEGFR-TK[T790M-L858R]) in C. elegans vulval cells using the let-23 promoter.
      The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and
      the activating mutant hEGFR-TK chimeras induced a multivulva (Muv) phenotype in a
      wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib
      suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic
      animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot
      screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an
      EGFR-TK inhibitor) and U0126 (a MEK inhibitor) were identified as potential
      inhibitors of EGFR-mediated biological function. In conclusion, transgenic C.
      elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can
      be used in mutation-specific screens for new anti-cancer drugs.

PMID- 22957021
TI  - Corticotropin-releasing hormone receptor 1 gene variants in irritable bowel
      syndrome.
AB  - BACKGROUND: Corticotropin-releasing hormone (CRH) acts mainly via the CRH
      receptor 1 (CRH-R1) and plays a crucial role in the stress-induced
      pathophysiology of irritable bowel syndrome (IBS). Several studies have
      demonstrated that variants of the CRH-R1 gene carry a potential risk for
      depression, but evidence for an association between CRH-R1 genotypes and IBS is
      lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of
      CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients. METHODS:
      A total of 103 patients with IBS and 142 healthy controls participated in the
      study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436,
      rs242924, and rs110402) were genotyped. Subjects' emotional states were evaluated
      using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self
      rating Depression Scale. RESULTS: The TT genotype of rs7209436 (P = 0.01) and
      rs242924 (P = 0.02) was significantly more common in patients with IBS than in
      controls. Total sample analysis showed significant association between bowel
      pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of
      rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P
      = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated
      with the examined CRH-R1 SNPs. CONCLUSION: These findings suggest that genetic
      polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns.
      There was no clear association between CRH-R1 genotypes and negative emotion
      accompanying IBS. Further studies on the CRH system are therefore warranted.

PMID- 22957022
TI  - Differential effects of short-term treatment with two AT1 receptor blockers on
      diameter of pial arterioles in SHR.
AB  - Chronic treatment with angiotensin receptor blockers is largely accepted for
      protecting cerebral circulation during hypertension, but beneficial effects of
      short-term treatments are questionable, as highlighted by the recent SCAST trial.
      We compared the impact of 10 days treatment with candesartan (as SCAST) versus
      telmisartan (previously described to reverse arteriolar remodeling, chronic
      treatment) on pial arterioles of spontaneously hypertensive rats (SHR). We
      explored whether PPAR-gamma agonist activity or AT(1) receptor blockade are
      involved in their differential effects. In the first study, 4-month-old male SHR
      were treated with telmisartan (TELMI, 2 mg/kg per day) or candesartan cilexetil
      (CANDE, 10 mg/kg per day) and compared to vehicle treated SHR and normotensive
      WKY. In a second study, SHR were treated with CANDE, pioglitazone (a PPAR-gamma
      agonist, PIO 2.5 mg/kg per day) or CANDE+PIO, compared to TELMI. Internal
      diameter of pial arterioles (ID, cranial window) was measured at baseline, during
      hemorrhage-induced hypotension, or following suffusion of Ang II (10(-6) mol/L)
      or EDTA inactivation of smooth muscle cells (passive ID). PPAR-gamma and eNOS
      (target gene of PPAR-gamma) mRNA were evaluated in brain microvessels. For
      similar antihypertensive effects, TELMI (+44% versus SHR), but not CANDE,
      increased baseline ID. During hemorrhage, ID in TELMI group was similar to WKY,
      while ID in SHR and CANDE remained lower. In the second study, TELMI (+36%,
      versus SHR) and CANDE+PIO (+43%) increased baseline ID, but not CANDE or PIO
      alone. TELMI (-66%) and CANDE+PIO (-69%), but neither CANDE nor PIO alone,
      decreased Ang II-induced vasoconstriction. CANDE+PIO, but not CANDE, increased
      passive ID. In both studies, PPAR-gamma and eNOS expressions were higher in TELMI
      than CANDE. Short-term treatment with TELMI, but not with CANDE, reverses
      narrowing of pial arteriolar ID in SHR. This may involve PPAR-gamma related
      mechanisms, since CANDE+PIO treatment induced similar effects, and a better
      blockade of AT(1) receptors.

PMID- 22957023
TI  - Differential glioma-associated tumor antigen expression profiles of human glioma
      cells grown in hypoxia.
AB  - Human U251 and D54 glioma cells were tested for expression of 25 glioma
      associated tumor antigen precursor proteins (TAPP) under hypoxic (1% O(2)) or
      normoxic (21% O(2)) conditions. Hypoxic glioma cell lines increased their mRNA
      expression for nine TAPP (Aim2, Art-4, EphA2, EZH2, Fosl1, PTH-rP, Sox 11, Whsc2
      and YKL-40), as assessed by quantitative reverse transcriptase real
      time/polymerase chain reaction (qRT-PCR). Increased differences with three
      hypoxic-induced TAPP: EZH2, Whsc2 and YKL-40 were shown at the protein levels by
      fluorescent antibody staining and quantitative electrophoretic analysis. Two TAPP
      (MRP3 and Trp1) were down-regulated by hypoxia in glioma cell lines. Growing the
      glioma cells under hypoxia for 13 days, followed by returning them back to
      normoxic conditions for 7 days, and restored the original normoxic TAPP profile.
      Thus, hypoxia was an environmental factor that stimulated the transient
      expression of these antigens. Intracranial xenografts grown in nude mice derived
      from U251 cells that had been cultured under neurosphere stem cell conditions
      showed increased expression of Whsc2 or YKL-40, demonstrating that these in vitro
      properties of glioma also occur in vivo. Whsc2-specific cytotoxic T lymphocytes
      killed the hypoxic U251 glioma cells better than normoxic glioma cells. The
      antigens expressed by hypoxic tumor cells may be a better source of starting
      tumor material for loading dendritic cells for novel immunotherapy of glioma
      using tumor-associated antigens.

PMID- 22957024
TI  - Identification of genes for complex diseases using integrated analysis of
      multiple types of genomic data.
AB  - Various types of genomic data (e.g., SNPs and mRNA transcripts) have been
      employed to identify risk genes for complex diseases. However, the analysis of
      these data has largely been performed in isolation. Combining these multiple data
      for integrative analysis can take advantage of complementary information and thus
      can have higher power to identify genes (and/or their functions) that would
      otherwise be impossible with individual data analysis. Due to the different
      nature, structure, and format of diverse sets of genomic data, multiple genomic
      data integration is challenging. Here we address the problem by developing a
      sparse representation based clustering (SRC) method for integrative data
      analysis. As an example, we applied the SRC method to the integrative analysis of
      376821 SNPs in 200 subjects (100 cases and 100 controls) and expression data for
      22283 genes in 80 subjects (40 cases and 40 controls) to identify significant
      genes for osteoporosis (OP). Comparing our results with previous studies, we
      identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1',
      'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1',
      'SPARC', and 'LRP1'). Moreover, we uncovered novel osteoporosis susceptible genes
      ('DICER1', 'PTMA', etc.) that were not found previously but play functionally
      important roles in osteoporosis etiology from existing studies. In addition, the
      SRC method identified genes can lead to higher accuracy for the
      diagnosis/classification of osteoporosis subjects when compared with the
      traditional T-test and Fisher-exact test, which further validates the proposed
      SRC approach for integrative analysis.

PMID- 22957025
TI  - Novel device to sample the esophageal microbiome--the esophageal string test.
AB  - A growing number of studies implicate the microbiome in the pathogenesis of
      intestinal inflammation. Previous work has shown that adults with esophagitis
      related to gastroesophageal reflux disease have altered esophageal microbiota
      compared to those who do not have esophagitis. In these studies, sampling of the
      esophageal microbiome was accomplished by isolating DNA from esophageal biopsies
      obtained at the time of upper endoscopy. The aim of the current study was to
      identify the esophageal microbiome in pediatric individuals with normal
      esophageal mucosa using a minimally invasive, capsule-based string technology,
      the EnterotestTM. We used the proximal segment of the Enterotest string to sample
      the esophagus, and term this the "Esophageal String Test" (EST). We hypothesized
      that the less invasive EST would capture mucosal adherent bacteria present in the
      esophagus in a similar fashion as mucosal biopsy. EST samples and mucosal
      biopsies were collected from children with no esophageal inflammation (n = 15)
      and their microbiome composition determined by 16S rRNA gene sequencing.
      Microbiota from esophageal biopsies and ESTs produced nearly identical profiles
      of bacterial genera and were different from the bacterial contents of samples
      collected from the nasal and oral cavity. We conclude that the minimally invasive
      EST can serve as a useful device for study of the esophageal microbiome.

PMID- 22957026
TI  - The VNTR polymorphism of the DC-SIGNR gene and susceptibility to HIV-1 infection:
      a meta-analysis.
AB  - BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing
      nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1
      (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen
      interaction in HIV-1 infection. Studies of the association between the variable
      number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1
      susceptibility have produced controversial results. METHODS AND FINDINGS: We
      conducted a meta-analysis of the data contained in the literature to clarify
      these findings. In total, 10 studies consisting of 2683 HIV-1 patients and 3263
      controls (2130 healthy controls and 1133 HIV-1 exposed but seronegative (HESN)
      controls) were included. Odds ratios (ORs) with 95% confidence intervals (95%
      CIs) were assessed in the main analyses. Further stratified analyses by ethnicity
      and sample size were performed. By dividing the controls into two groups, healthy
      controls and HIV-1 exposed but seronegative (HESN) controls, we explored
      different genetic models to detect any association between the VNTR polymorphism
      and predisposition to HIV-1 infection. The results showed that the 5-repeat
      allele carriers (OR = 0.84, 95% CI = 0.73-0.96) and the 5/5 homozygous (OR =
      0.68, 95% CI = 0.50-0.93) had significantly reduced risk when using the HIV-1
      exposed but seronegative (HESN) as controls. The stratified analyses by ethnicity
      and sample size confirmed these findings. However, a low to moderate degree of
      heterogeneity was also found across studies. CONCLUSIONS: Our findings
      demonstrate that the VNTR polymorphism of the DC-SIGNR gene is associated with a
      moderate effect on host susceptibility to HIV-1 infection. Similar to the 32-bp
      deletion in the chemokine receptor-5 gene (CCR5Delta32), the DC-SIGNR VNTR 5
      repeat allele might have a role in resistance to HIV infection, particularly in
      Asian populations.

PMID- 22957027
TI  - Trees of unusual size: biased inference of early bursts from large molecular
      phylogenies.
AB  - An early burst of speciation followed by a subsequent slowdown in the rate of
      diversification is commonly inferred from molecular phylogenies. This pattern is
      consistent with some verbal theory of ecological opportunity and adaptive
      radiations. One often-overlooked source of bias in these studies is that of
      sampling at the level of whole clades, as researchers tend to choose large,
      speciose clades to study. In this paper, we investigate the performance of common
      methods across the distribution of clade sizes that can be generated by a
      constant-rate birth-death process. Clades which are larger than expected for a
      given constant-rate branching process tend to show a pattern of an early burst
      even when both speciation and extinction rates are constant through time. All
      methods evaluated were susceptible to detecting this false signature when
      extinction was low. Under moderate extinction, both the [Formula: see text]
      statistic and diversity-dependent models did not detect such a slowdown but only
      because the signature of a slowdown was masked by subsequent extinction. Some
      models which estimate time-varying speciation rates are able to detect early
      bursts under higher extinction rates, but are extremely prone to sampling bias.
      We suggest that examining clades in isolation may result in spurious inferences
      that rates of diversification have changed through time.

PMID- 22957028
TI  - Publication bias in laboratory animal research: a survey on magnitude, drivers,
      consequences and potential solutions.
AB  - CONTEXT: Publication bias jeopardizes evidence-based medicine, mainly through
      biased literature syntheses. Publication bias may also affect laboratory animal
      research, but evidence is scarce. OBJECTIVES: To assess the opinion of laboratory
      animal researchers on the magnitude, drivers, consequences and potential
      solutions for publication bias. And to explore the impact of size of the animals
      used, seniority of the respondent, working in a for-profit organization and type
      of research (fundamental, pre-clinical, or both) on those opinions. DESIGN:
      Internet-based survey. SETTING: All animal laboratories in The Netherlands.
      PARTICIPANTS: Laboratory animal researchers. MAIN OUTCOME MEASURE(S): Median
      (interquartile ranges) strengths of beliefs on 5 and 10-point scales (1: totally
      unimportant to 5 or 10: extremely important). RESULTS: Overall, 454 researchers
      participated. They considered publication bias a problem in animal research (7 (5
      to 8)) and thought that about 50% (32-70) of animal experiments are published.
      Employees (n = 21) of for-profit organizations estimated that 10% (5 to 50) are
      published. Lack of statistical significance (4 (4 to 5)), technical problems (4
      (3 to 4)), supervisors (4 (3 to 5)) and peer reviewers (4 (3 to 5)) were
      considered important reasons for non-publication (all on 5-point scales).
      Respondents thought that mandatory publication of study protocols and results, or
      the reasons why no results were obtained, may increase scientific progress but
      expected increased bureaucracy. These opinions did not depend on size of the
      animal used, seniority of the respondent or type of research. CONCLUSIONS: Non
      publication of "negative" results appears to be prevalent in laboratory animal
      research. If statistical significance is indeed a main driver of publication, the
      collective literature on animal experimentation will be biased. This will impede
      the performance of valid literature syntheses. Effective, yet efficient systems
      should be explored to counteract selective reporting of laboratory animal
      research.

PMID- 22957029
TI  - Utilization of sugarcane habitat by feral pig (Sus scrofa) in northern tropical
      Queensland: evidence from the stable isotope composition of hair.
AB  - Feral pigs (Sus scrofa) are an invasive species that disrupt ecosystem
      functioning throughout their introduced range. In tropical environments, feral
      pigs are associated with predation and displacement of endangered species,
      modification of habitat, and act as a vector for the spread of exotic vegetation
      and disease. Across many parts of their introduced range, the diet of feral pigs
      is poorly known. Although the remote location and difficult terrain of far north
      Queensland makes observing feral pig behavior difficult, feral pigs are perceived
      to seek refuge in World Heritage tropical rainforests and seasonally 'crop raid'
      into lowland sugarcane crops. Thus, identifying how feral pigs are using
      different components of the landscape is important to the design of management
      strategies. We used the stable isotope composition of captured feral pigs to
      determine the extent of rainforest and sugarcane habitat usage. Recently grown
      hair (basal hair) from feral pigs captured in remote rainforest indicated pigs
      met their dietary needs solely within this habitat. Stable carbon and nitrogen
      isotope values of basal hair from feral pigs captured near sugarcane plantations
      were more variable, with some individuals estimated to consume over 85% of their
      diet within a sugarcane habitat, while a few consumed as much as 90% of their
      diet from adjacent forested environments. We estimated whether feral pigs switch
      habitats by sequentially sampling delta(13)C and delta(15)N values of long tail
      hair from a subset of seven captured animals, and demonstrate that four of these
      individuals moved between habitats. Our results indicate that feral pigs utilize
      both sugarcane and forest habitats, and can switch between these resources.

PMID- 22957030
TI  - Effects of timber harvest on river food webs: physical, chemical and biological
      responses.
AB  - I compared physical, chemical and biological characteristics of nine rivers
      running through three timber harvest regimes to investigate the effects of land
      use on river ecosystems, to determine whether these corresponded to changes
      linked with downstream location, and to compare the response of different types
      of indicator variables. Physical variables changed with downstream location, but
      varied little with timber harvest. Most chemical variables increased strongly
      with timber harvest, but not with downstream location. Most biological variables
      did not vary systematically with either timber harvest or downstream location.
      Dissolved organic carbon did not vary with timber harvest or downstream location,
      but correlated positively with salmonid abundance. Nutrient manipulations
      revealed no general pattern of nutrient limitation with timber harvest or
      downstream location. The results suggest that chemical variables most reliably
      indicate timber harvest impact in these systems. The biological variables most
      relevant to human stakeholders were surprisingly insensitive to timber harvest,
      however, apparently because of decoupling from nutrient responses and
      unexpectedly weak responses by physical variables.

PMID- 22957031
TI  - Developmental heterogeneity in DNA packaging patterns influences T-cell
      activation and transmigration.
AB  - Cellular differentiation programs are accompanied by large-scale changes in
      nuclear organization and gene expression. In this context, accompanying
      transitions in chromatin assembly that facilitates changes in gene expression and
      cell behavior in a developmental system are poorly understood. Here, we address
      this gap and map structural changes in chromatin organization during murine T
      cell development, to describe an unusual heterogeneity in chromatin organization
      and associated functional correlates in T-cell lineage. Confocal imaging of DNA
      assembly in cells isolated from bone marrow, thymus and spleen reveal the
      emergence of heterogeneous patterns in DNA organization in mature T-cells
      following their exit from the thymus. The central DNA pattern dominated in
      immature precursor cells in the thymus whereas both central and peripheral DNA
      patterns were observed in naive and memory cells in circulation. Naive T-cells
      with central DNA patterns exhibited higher mechanical pliability in response to
      compressive loads in vitro and transmigration assays in vivo, and demonstrated
      accelerated expression of activation-induced marker CD69. T-cell activation was
      characterized by marked redistribution of DNA assembly to a central DNA pattern
      and increased nuclear size. Notably, heterogeneity in DNA patterns recovered in
      cells induced into quiescence in culture, suggesting an internal regulatory
      mechanism for chromatin reorganization. Taken together, our results uncover an
      important component of plasticity in nuclear organization, reflected in chromatin
      assembly, during T-cell development, differentiation and transmigration.

PMID- 22957032
TI  - Combinatorial treatment of DNA and chromatin-modifying drugs cause cell death in
      human and canine osteosarcoma cell lines.
AB  - Downregulation of microRNAs (miRNAs) at the 14q32 locus stabilizes the expression
      of cMYC, thus significantly contributing to osteosarcoma (OS) pathobiology. Here,
      we show that downregulation of 14q32 miRNAs is epigenetically regulated. The
      predicted promoter regions of miRNA clusters at 14q32 locus showed no recurrent
      patterns of differential methylation, but Saos2 cells showed elevated histone
      deacetylase (HDAC) activity. Treatment with 4-phenylbutyrate increased
      acetylation of histones associated with 14q32 miRNAs, but interestingly, robust
      restoration of 14q32 miRNA expression, attenuation of cMYC expression, and
      induction of apoptosis required concomitant treatment with 5-Azacytidine, an
      inhibitor of DNA methylation. These events were associated with genome-wide gene
      expression changes including induction of pro-apoptotic genes and downregulation
      of cell cycle genes. Comparable effects were achieved in human and canine OS
      cells using the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat)
      and the DNA methylation inhibitor Zebularine (Zeb), with significantly more
      pronounced cytotoxicity in cells whose molecular phenotypes were indicative of
      aggressive biological behavior. These results suggested that the combination of
      these chromatin-modifying drugs may be a useful adjuvant in the treatment of
      rapidly progressive OS.

PMID- 22957033
TI  - Suppression of cancer progression by MGAT1 shRNA knockdown.
AB  - Oncogenic signaling promotes tumor invasion and metastasis, in part, by
      increasing the expression of tri- and tetra- branched N-glycans. The branched N
      glycans bind to galectins forming a multivalent lattice that enhances cell
      surface residency of growth factor receptors, and focal adhesion turnover. N
      acetylglucosaminyltransferase I (MGAT1), the first branching enzyme in the
      pathway, is required for the addition of all subsequent branches. Here we have
      introduced MGAT1 shRNA into human HeLa cervical and PC-3-Yellow prostate tumor
      cells lines, generating cell lines with reduced transcript, enzyme activity and
      branched N-glycans at the cell surface. MGAT1 knockdown inhibited HeLa cell
      migration and invasion, but did not alter cell proliferation rates. Swainsonine,
      an inhibitor of alpha-mannosidase II immediately downstream of MGAT1, also
      inhibited cell invasion and was not additive with MGAT1 shRNA, consistent with a
      common mechanism of action. Focal adhesion and microfilament organization in
      MGAT1 knockdown cells also indicate a less motile phenotype. In vivo, MGAT1
      knockdown in the PC-3-Yellow orthotopic prostate cancer xenograft model
      significantly decreased primary tumor growth and the incidence of lung
      metastases. Our results demonstrate that blocking MGAT1 is a potential target for
      anti-cancer therapy.

PMID- 22957034
TI  - Text messaging to improve attendance at post-operative clinic visits after adult
      male circumcision for HIV prevention: a randomized controlled trial.
AB  - BACKGROUND: Following male circumcision for HIV prevention, a high proportion of
      men fail to return for their scheduled seven-day post-operative visit. We
      evaluated the effect of short message service (SMS) text messages on attendance
      at this important visit. METHODOLOGY: We enrolled 1200 participants >18 years old
      in a two-arm, parallel, randomized controlled trial at 12 sites in Nyanza
      province, Kenya. Participants received daily SMS text messages for seven days (n
      = 600) or usual care (n = 600). The primary outcome was attendance at the
      scheduled seven-day post-operative visit. The primary analysis was by intention
      to-treat. PRINCIPAL FINDINGS: Of participants receiving SMS, 387/592 (65.4%)
      returned, compared to 356/596 (59.7%) in the control group (relative risk [RR] =
      1.09, 95% confidence interval [CI] 1.00-1.20; p = 0.04). Men who paid more than
      US$1.25 to travel to clinic were at higher risk for failure to return compared to
      those who spent <= US$1.25 (adjusted relative risk [aRR] 1.35, 95% CI 1.15-1.58;
      p<0.001). Men with secondary or higher education had a lower risk of failure to
      return compared to those with primary or less education (aRR 0.87, 95% CI 0.74
      1.01; p = 0.07). CONCLUSIONS: Text messaging resulted in a modest improvement in
      attendance at the 7-day post-operative clinic visit following adult male
      circumcision. Factors associated with failure to return were mainly structural,
      and included transportation costs and low educational level. TRIAL REGISTRATION:
      ClinicalTrials.govNCT01186575.

PMID- 22957035
TI  - Is "circling" behavior in humans related to postural asymmetry?
AB  - In attempting to walk rectilinearly in the absence of visual landmarks, persons
      will gradually turn in a circle to eventually become lost. The aim of the present
      study was to provide insights into the possible underlying mechanisms of this
      behavior. For each subject (N = 15) six trajectories were monitored during
      blindfolded walking in a large enclosed area to suppress external cues, and
      ground irregularities that may elicit unexpected changes in direction. There was
      a substantial variability from trial to trial for a given subject and between
      subjects who could either veer very early or relatively late. Of the total number
      of trials, 50% trajectories terminated on the left side, 39% on the right side
      and 11% were defined as "straight". For each subject, we established a "turning
      score" that reflected his/her preferential side of veering. The turning score was
      found to be unrelated to any evident biomechanical asymmetry or functional
      dominance (eye, hand...). Posturographic analysis, used to assess if there was a
      relationship between functional postural asymmetry and veering revealed that the
      mean position of the center of foot pressure during balance tests was correlated
      with the turning score. Finally, we established that the mean position of the
      center of pressure was correlated with perceived verticality assessed by a
      subjective verticality test. Together, our results suggest that veering is
      related to a "sense of straight ahead" that could be shaped by vestibular inputs.

PMID- 22957036
TI  - Anxiogenic effects of developmental bisphenol A exposure are associated with gene
      expression changes in the juvenile rat amygdala and mitigated by soy.
AB  - Early life exposure to Bisphenol A (BPA), a component of polycarbonate plastics
      and epoxy resins, alters sociosexual behavior in numerous species including
      humans. The present study focused on the ontogeny of these behavioral effects
      beginning in adolescence and assessed the underlying molecular changes in the
      amygdala. We also explored the mitigating potential of a soy-rich diet on these
      endpoints. Wistar rats were exposed to BPA via drinking water (1 mg/L) from
      gestation through puberty, and reared on a soy-based or soy-free diet. A group
      exposed to ethinyl estradiol (50 ug/L) and a soy-free diet was used as a positive
      estrogenic control. Animals were tested as juveniles or adults for anxiety-like
      and exploratory behavior. Assessment of serum BPA and genistein (GEN), a soy
      phytoestrogen, confirmed that internal dose was within a human-relevant range.
      BPA induced anxiogenic behavior in juveniles and loss of sexual dimorphisms in
      adult exploratory behavior, but only in the animals reared on the soy-free diet.
      Expression analysis revealed a suite of genes, including a subset known to
      mediate sociosexual behavior, associated with BPA-induced juvenile anxiety.
      Notably, expression of estrogen receptor beta (Esr2) and two melanocortin
      receptors (Mc3r, Mc4r) were downregulated. Collectively, these results show that
      behavioral impacts of BPA can manifest during adolescence, but wane in adulthood,
      and may be mitigated by diet. These data also reveal that, because ERbeta and
      melanocortin receptors are crucial to their function, oxytocin/vasopressin
      signaling pathways, which have previously been linked to human affective
      disorders, may underlie these behavioral outcomes.

PMID- 22957037
TI  - Miiuy croaker transferrin gene and evidence for positive selection events reveal
      different evolutionary patterns.
AB  - Transferrin (TF) is a protein that plays a central role in iron metabolism. This
      protein is associated with the innate immune system, which is responsible for
      disease defense responses after bacterial infection. The clear link between TF
      and the immune defense mechanism has led researchers to consider TF as a
      candidate gene for disease resistance. In this study, the Miichthys miiuy (miiuy
      croaker) TF gene (MIMI-TF) was cloned and characterized. The gene structure
      consisted of a coding region of 2070 nucleotides divided into 17 exons, as well
      as a non-coding region that included 16 introns and spans 6757 nucleotides. The
      deduced MIMI-TF protein consisted of 689 amino acids that comprised a signal
      peptide and two lobes (N- and C-lobes). MIMI-TF expression was significantly up
      regulated after infection with Vibrio anguillarum. A series of model tests
      implemented in the CODEML program showed that TF underwent a complex evolutionary
      process. Branch-site models revealed that vertebrate TF was vastly different from
      that of invertebrates, and that the TF of the ancestors of aquatic and
      terrestrial organisms underwent different selection pressures. The site models
      detected 10 positively selected sites in extant TF genes. One site was located in
      the cleft between the N1 and N2 domains and was expected to affect the capability
      of TF to bind to or release iron indirectly. In addition, eight sites were found
      near the TF exterior. Two of these sites, which could have evolved from the
      competition for iron between pathogenic bacteria and TF, were located in
      potential pathogen-binding domains. Our results could be used to further
      investigate the function of TF and the selective mechanisms involved.

PMID- 22957038
TI  - Activation of NF-kappaB in basolateral amygdala is required for memory
      reconsolidation in auditory fear conditioning.
AB  - Posttraumatic stress disorder (PTSD) is characterized by acute and chronic
      changes in the stress response, manifested as conditioned fear memory. Previously
      formed memories that are susceptible to disruption immediately after retrieval
      undergo a protein synthesis-dependent process to become persistent, termed
      reconsolidation, a process that is regulated by many distinct molecular
      mechanisms that control gene expression. Increasing evidence supports the
      participation of the transcription factor NF-kappaB in the different phases of
      memory. Here, we demonstrate that inhibition of NF-kappaB in the basolateral
      amygdala (BLA), but not central nucleus of the amygdala, after memory
      reactivation impairs the retention of amygdala-dependent auditory fear
      conditioning (AFC). We used two independent pharmacological strategies to disrupt
      the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an
      inhibitor of IkappaB kinase that activates NF-kappaB, and bilateral intra-BLA
      infusion of SN50, a direct inhibitor of the NF-kappaB DNA-binding complex,
      immediately after retrieval disrupted the reconsolidation of AFC. We also found
      that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor
      that enhances histone acetylation, in the amygdala rescued the disruption of
      reconsolidation induced by NF-kappaB inhibition in the BLA. These findings
      indicate that NF-kappaB activity in the BLA is required for memory
      reconsolidation in AFC, suggesting that NF-kappaB might be a potential
      pharmacotherapy target for posttraumatic stress disorder.

PMID- 22957039
TI  - Candidate polymorphisms and severe malaria in a Malian population.
AB  - Malaria is a major health burden in sub-Saharan African countries, including
      Mali. The disease is complex, with multiple genetic determinants influencing the
      observed variation in response to infection, progression, and severity. We assess
      the influence of sixty-four candidate loci, including the sickle cell
      polymorphism (HbS), on severe malaria in a case-control study consisting of over
      900 individuals from Bamako, Mali. We confirm the known protective effects of the
      blood group O and the HbS AS genotype on life-threatening malaria. In addition,
      our analysis revealed a marginal susceptibility effect for the CD40 ligand
      (CD40L)+220C allele. The lack of statistical evidence for other candidates may
      demonstrate the need for large-scale genome-wide association studies in malaria
      to discover new polymorphisms. It also demonstrates the need for establishing the
      region-specific repertoire of functional variation in important genes, including
      the glucose-6-phosphatase deficiency gene, before embarking on focused
      genotyping.

PMID- 22957040
TI  - A practical simulation method to calculate sample size of group sequential trials
      for time-to-event data under exponential and Weibull distribution.
AB  - Group sequential design has been widely applied in clinical trials in the past
      few decades. The sample size estimation is a vital concern of sponsors and
      investigators. Especially in the survival group sequential trials, it is a thorny
      question because of its ambiguous distributional form, censored data and
      different definition of information time. A practical and easy-to-use simulation
      based method is proposed for multi-stage two-arm survival group sequential design
      in the article and its SAS program is available. Besides the exponential
      distribution, which is usually assumed for survival data, the Weibull
      distribution is considered here. The incorporation of the probability of
      discontinuation in the simulation leads to the more accurate estimate. The
      assessment indexes calculated in the simulation are helpful to the determination
      of number and timing of the interim analysis. The use of the method in the
      survival group sequential trials is illustrated and the effects of the varied
      shape parameter on the sample size under the Weibull distribution are explored by
      employing an example. According to the simulation results, a method to estimate
      the shape parameter of the Weibull distribution is proposed based on the median
      survival time of the test drug and the hazard ratio, which are prespecified by
      the investigators and other participants. 10+ simulations are recommended to
      achieve the robust estimate of the sample size. Furthermore, the method is still
      applicable in adaptive design if the strategy of sample size scheme determination
      is adopted when designing or the minor modifications on the program are made.

PMID- 22957041
TI  - Depletion of the C. elegans NAC engages the unfolded protein response, resulting
      in increased chaperone expression and apoptosis.
AB  - The nascent polypeptide-associated complex (NAC) is a highly conserved
      heterodimer important for metazoan development, but its molecular function is not
      well understood. Recent evidence suggests the NAC is a component of the cytosolic
      chaperone network that interacts with ribosomal complexes and their emerging
      nascent peptides, such that the loss of the NAC in chaperone-depleted cells
      results in an increase in misfolded protein stress. We tested whether the NAC
      functions similarly in Caeonorhabditis (C.) elegans and found that its homologous
      NAC subunits, i.e. ICD-1 and -2, have chaperone-like characteristics. Loss of the
      NAC appears to induce misfolded protein stress in the ER triggering the unfolded
      protein response (UPR). Depletion of the NAC altered the response to heat stress,
      and led to an up-regulation of hsp-4, a homologue of the human chaperone and ER
      stress sensor GRP78/BiP. Worms lacking both ICD-1 and the UPR transcription
      factor XBP-1 generated a higher proportion of defective embryos, showed increased
      embryonic apoptosis and had a diminished survival rate relative to ICD-1-depleted
      animals with an intact UPR. Up-regulation of hsp-4 in NAC-depleted animals was
      specific to certain regions of the embryo; in embryos lacking ICD-1, the
      posterior region of the embryo showed strong up-regulation of hsp-4, while the
      anterior region did not. Furthermore, loss of ICD-1 produced prominent lysosomes
      in the gut region of adults and embryos putatively containing lipofuscins,
      lipid/protein aggregates associated with cellular aging. These results are the
      first set of evidence consistent with a role for C. elegans NAC in protein
      folding and localization during translation. Further, these findings confirm C.
      elegans as a valuable model for studying organismal and cell-type specific
      responses to misfolded protein stress.

PMID- 22957042
TI  - Magneto-electric nano-particles for non-invasive brain stimulation.
AB  - This paper for the first time discusses a computational study of using magneto
      electric (ME) nanoparticles to artificially stimulate the neural activity deep in
      the brain. The new technology provides a unique way to couple electric signals in
      the neural network to the magnetic dipoles in the nanoparticles with the purpose
      to enable a non-invasive approach. Simulations of the effect of ME nanoparticles
      for non-invasively stimulating the brain of a patient with Parkinson's Disease to
      bring the pulsed sequences of the electric field to the levels comparable to
      those of healthy people show that the optimized values for the concentration of
      the 20-nm nanoparticles (with the magneto-electric (ME) coefficient of 100 V cm(
      1) Oe(-1) in the aqueous solution) is 3 * 10(6) particles/cc, and the frequency
      of the externally applied 300-Oe magnetic field is 80 Hz.

PMID- 22957043
TI  - Promoting household water treatment through women's self help groups in Rural
      India: assessing impact on drinking water quality and equity.
AB  - Household water treatment, including boiling, chlorination and filtration, has
      been shown effective in improving drinking water quality and preventing diarrheal
      disease among vulnerable populations. We used a case-control study design to
      evaluate the extent to which the commercial promotion of household water filters
      through microfinance institutions to women's self-help group (SHG) members
      improved access to safe drinking water. This pilot program achieved a 9.8%
      adoption rate among women targeted for adoption. Data from surveys and assays of
      fecal contamination (thermotolerant coliforms, TTC) of drinking water samples
      (source and household) were analyzed from 281 filter adopters and 247 non
      adopters exposed to the program; 251 non-SHG members were also surveyed. While
      adopters were more likely than non-adopters to have children under 5 years, they
      were also more educated, less poor, more likely to have access to improved water
      supplies, and more likely to have previously used a water filter. Adopters had
      lower levels of fecal contamination of household drinking water than non
      adopters, even among those non-adopters who treated their water by boiling or
      using traditional ceramic filters. Nevertheless, one-third of water samples from
      adopter households exceeded 100 TTC/100ml (high risk), and more than a quarter of
      the filters had no stored treated water available when visited by an
      investigator, raising concerns about correct, consistent use. In addition, the
      poorest adopters were less likely to see improvements in their water quality.
      Comparisons of SHG and non-SHG members suggest similar demographic
      characteristics, indicating SHG members are an appropriate target group for this
      promotion campaign. However, in order to increase the potential for health gains,
      future programs will need to increase uptake, particularly among the poorest
      households who are most susceptible to disease morbidity and mortality, and focus
      on strategies to improve the correct, consistent and sustained use of these water
      treatment products.

PMID- 22957044
TI  - Computational studies on the substrate interactions of influenza A virus PB2
      subunit.
AB  - Influenza virus, which spreads around the world in seasonal epidemics and leads
      to large numbers of deaths every year, has several ribonucleoproteins in the
      central core of the viral particle. These viral ribonucleoproteins can
      specifically bind the conserved 3' and 5' caps of the viral RNAs with
      responsibility for replication and transcription of the viral RNA in the nucleus
      of infected cells. A fundamental question of most importance is that how the cap
      binding proteins in the influenza virus discriminates between capped RNAs and non
      capped ones. To get an answer, we performed molecular dynamics simulations and
      free energy calculations on the influenza A virus PB2 subunit, an important
      component of the RNP complexes, with a cap analog m7GTP. Our calculations showed
      that some key residues in the active site, such as Arg355, His357, Glu361 as well
      as Gln406, could offer significant hydrogen bonding and hydrophobic interactions
      with the guanine ring of the cap analog m7GTP to form an aromatic sandwich
      mechanism for the cap recognition and positioning in the active site.
      Subsequently, we applied this idea to a virtual screening procedure and
      identified 5 potential candidates that might be inhibitors against the PB2
      subunit. Interestingly, 2 candidates Cpd1 and Cpd2 have been already reported to
      have inhibitory activities to the influenza virus cap-binding proteins. Further
      calculation also showed that they had comparatively higher binding affinities to
      the PB2 subunit than that of m7GTP. We believed that our findings could give an
      atomic insight into the deeper understanding of the cap recognition and binding
      mechanism, providing useful information for searching or designing novel drugs
      against influenza viruses.

PMID- 22957045
TI  - Nitric oxide synthase and breast cancer: role of TIMP-1 in NO-mediated Akt
      activation.
AB  - Prediction of therapeutic response and cancer patient survival can be improved by
      the identification of molecular markers including tumor Akt status. A direct
      correlation between NOS2 expression and elevated Akt phosphorylation status has
      been observed in breast tumors. Tissue inhibitor matrix metalloproteinase-1 (TIMP
      1) has been proposed to exert oncogenic properties through CD63 cell surface
      receptor pathway initiation of pro-survival PI3k/Akt signaling. We employed
      immunohistochemistry to examine the influence of TIMP-1 on the functional
      relationship between NOS2 and phosphorylated Akt in breast tumors and found that
      NOS2-associated Akt phosphorylation was significantly increased in tumors
      expressing high TIMP-1, indicating that TIMP-1 may further enhance NO-induced Akt
      pathway activation. Moreover, TIMP-1 silencing by antisense technology blocked NO
      induced PI3k/Akt/BAD phosphorylation in cultured MDA-MB-231 human breast cancer
      cells. TIMP-1 protein nitration and TIMP-1/CD63 co-immunoprecipitation was
      observed at NO concentrations that induced PI3k/Akt/BAD pro-survival signaling.
      In the survival analysis, elevated tumor TIMP-1 predicted poor patient survival.
      This association appears to be mainly restricted to tumors with high NOS2
      protein. In contrast, TIMP-1 did not predict poor survival in patient tumors with
      low NOS2 expression. In summary, our findings suggest that tumors with high TIMP
      1 and NOS2 behave more aggressively by mechanisms that favor Akt pathway
      activation.

PMID- 22957046
TI  - Differential role of Axin RGS domain function in Wnt signaling during
      anteroposterior patterning and maternal axis formation.
AB  - Axin is a critical component of the beta-catenin destruction complex and is also
      necessary for Wnt signaling initiation at the level of co-receptor activation.
      Axin contains an RGS domain, which is similar to that of proteins that accelerate
      the GTPase activity of heterotrimeric Galpha/Gna proteins and thereby limit the
      duration of active G-protein signaling. Although G-proteins are increasingly
      recognized as essential components of Wnt signaling, it has been unclear whether
      this domain of Axin might function in G-protein regulation. This study was
      performed to test the hypothesis that Axin RGS-Gna interactions would be required
      to attenuate Wnt signaling. We tested these ideas using an axin1 genetic mutant
      (masterblind) and antisense oligo knockdowns in developing zebrafish and Xenopus
      embryos. We generated a point mutation that is predicted to reduce Axin-Gna
      interaction and tested for the ability of the mutant forms to rescue Axin loss-of
      function function. This Axin point mutation was deficient in binding to Gna
      proteins in vitro, and was unable to relocalize to the plasma membrane upon Gna
      overexpression. We found that the Axin point mutant construct failed to rescue
      normal anteroposterior neural patterning in masterblind mutant zebrafish,
      suggesting a requirement for G-protein interactions in this context. We also
      found that the same mutant was able to rescue deficiencies in maternal axin1 loss
      of-function in Xenopus. These data suggest that maternal and zygotic Wnt
      signaling may differ in the extent of Axin regulation of G-protein signaling. We
      further report that expression of a membrane-localized Axin construct is
      sufficient to inhibit Wnt/beta-catenin signaling and to promote Axin protein
      turnover.

PMID- 22957047
TI  - Transposable elements in TDP-43-mediated neurodegenerative disorders.
AB  - Elevated expression of specific transposable elements (TEs) has been observed in
      several neurodegenerative disorders. TEs also can be active during normal
      neurogenesis. By mining a series of deep sequencing datasets of protein-RNA
      interactions and of gene expression profiles, we uncovered extensive binding of
      TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral
      sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find
      that association between TDP-43 and many of its TE targets is reduced in FTLD
      patients. Third, we discovered that a large fraction of the TEs to which TDP-43
      binds become de-repressed in mouse TDP-43 disease models. We propose the
      hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative
      diseases.

PMID- 22957048
TI  - Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence
      of specific antibodies against antibiotic-resistant pneumococcal strains.
AB  - BACKGROUND: Specific antibodies mediate humoral and cellular protection against
      invading pathogens such as Streptococcus pneumoniae by activating complement
      mediated immunity, promoting phagocytosis and stimulating bacterial clearance.
      The emergence of pneumococcal strains with high levels of antibiotic resistance
      is of great concern worldwide and a serious threat for public health.
      METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether
      complement-mediated immunity against three antibiotic-resistant S. pneumoniae
      clinical isolates is enhanced in the presence of sub-inhibitory concentrations of
      cefditoren and ceftriaxone. The binding of acute phase proteins such as C
      reactive protein and serum amyloid P component, and of complement component C1q,
      to pneumococci was enhanced in the presence of serum plus either of these
      antibiotics. Both antibiotics therefore trigger the activation of the classical
      complement pathway against S. pneumoniae. C3b deposition was also increased in
      the presence of specific anti-pneumococcal antibodies and sub-inhibitory
      concentrations of cefditoren and ceftriaxone confirming that the presence of
      these antibiotics enhances complement-mediated immunity to S. pneumoniae.
      CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding
      of acute phase proteins and C1q to pneumococci, and to increase C3b deposition,
      when anti-pneumococcal antibodies are present, might help reduce the impact of
      antibiotic resistance in S. pneumoniae infections.

PMID- 22957049
TI  - Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor
      methylation and expression in rat fetus.
AB  - Adverse fetal environment due to maternal undernutrition or exposure to
      environmental chemicals alters glucocorticoid (GC) metabolism increasing the risk
      of metabolic disorders in adulthood. In this study, we investigated the effects
      of maternal exposure to cadmium (Cd, 50 ppm) during pregnancy in the methylation
      of fetal hepatic glucocorticoid receptor promoter (GR) and the correlation with
      its expression and that of the DNA methyltransferases (DNMT1a and 3a). We also
      studied the expression of liver phosphoenolpyruvate carboxykinase (PEPCK) and
      acyl-CoA oxidase (AOX), two enzymes involved in the metabolism of carbohydrates
      and lipids respectively. The methylation of the rat GR gene exon 1(10) (GR1(10))
      in nucleotides -2536 to -2361 was analyzed by pyrosequencing. Quantitative real
      time PCR was used to assess hepatic GR, PEPCK and AOX mRNA, and their protein
      levels using Western blotting analysis. Differential methylation was noted across
      groups at all CpG sites in the GR exon 1(10) in a sex-dependent manner. In males,
      CpG were more methylated than the controls (185 +/- 21%, p<0.001) but only CpG
      sites 1,6,7 and 9 showed a significantly different extent of methylation. In
      addition, a lower expression of GR (mRNA and protein) was found. On the contrary,
      in females, CpG were less methylated than the controls (62 +/- 11%, p<0.05) and
      overexpressed, affecting PEPCK and AOX expression, which did not change in males.
      The GR methylation profile correlates with DNMT3a expression which may explain
      epigenetic sex-dependent changes on GR1(10) promoter induced by Cd treatment. In
      conclusion, Cd exposure during pregnancy affects fetal liver DNMT3a resulting in
      sex-dependent changes in methylation and expression of GR1(10). Although these
      effects do not seem to be directly involved in the low birth weight and height,
      they may have relevant implications for long-term health.

PMID- 22957050
TI  - A new avenue for classification and prediction of olive cultivars using
      supervised and unsupervised algorithms.
AB  - Various methods have been used to identify cultivares of olive trees; herein we
      used different bioinformatics algorithms to propose new tools to classify 10
      cultivares of olive based on RAPD and ISSR genetic markers datasets generated
      from PCR reactions. Five RAPD markers (OPA0a21, OPD16a, OP01a1, OPD16a1 and
      OPA0a8) and five ISSR markers (UBC841a4, UBC868a7, UBC841a14, U12BC807a and
      UBC810a13) selected as the most important markers by all attribute weighting
      models. K-Medoids unsupervised clustering run on SVM dataset was fully able to
      cluster each olive cultivar to the right classes. All trees (176) induced by
      decision tree models generated meaningful trees and UBC841a4 attribute clearly
      distinguished between foreign and domestic olive cultivars with 100% accuracy.
      Predictive machine learning algorithms (SVM and Naive Bayes) were also able to
      predict the right class of olive cultivares with 100% accuracy. For the first
      time, our results showed data mining techniques can be effectively used to
      distinguish between plant cultivares and proposed machine learning based systems
      in this study can predict new olive cultivars with the best possible accuracy.

PMID- 22957051
TI  - A novel computational strategy to identify A-to-I RNA editing sites by RNA-Seq
      data: de novo detection in human spinal cord tissue.
AB  - RNA editing is a post-transcriptional process occurring in a wide range of
      organisms. In human brain, the A-to-I RNA editing, in which individual adenosine
      (A) bases in pre-mRNA are modified to yield inosine (I), is the most frequent
      event. Modulating gene expression, RNA editing is essential for cellular
      homeostasis. Indeed, its deregulation has been linked to several neurological and
      neurodegenerative diseases. To date, many RNA editing sites have been identified
      by next generation sequencing technologies employing massive transcriptome
      sequencing together with whole genome or exome sequencing. While genome and
      transcriptome reads are not always available for single individuals, RNA-Seq data
      are widespread through public databases and represent a relevant source of yet
      unexplored RNA editing sites. In this context, we propose a simple computational
      strategy to identify genomic positions enriched in novel hypothetical RNA editing
      events by means of a new two-steps mapping procedure requiring only RNA-Seq data
      and no a priori knowledge of RNA editing characteristics and genomic reads. We
      assessed the suitability of our procedure by confirming A-to-I candidates using
      conventional Sanger sequencing and performing RNA-Seq as well as whole exome
      sequencing of human spinal cord tissue from a single individual.

PMID- 22957052
TI  - Functional metagenomics of Escherichia coli O157:H7 interactions with spinach
      indigenous microorganisms during biofilm formation.
AB  - The increase in foodborne outbreaks worldwide attributed to fresh fruit and
      vegetables suggests that produce may serve as an ecological niche for enteric
      pathogens. Here we examined the interaction of E. coli O157:H7 (EcO157) with
      spinach leaf indigenous microorganisms during co-colonization and establishment
      of a mixed biofilm on a stainless steel surface. Stainless steel surface was
      selected to mimic the surface of produce-processing equipment, where retention of
      foodborne pathogens such as EcO157 could serve as a potential source for
      transmission. We observed a positive effect of spinach-associated microbes on the
      initial attachment of EcO157, but an antagonistic effect on the EcO157 population
      at the later stage of biofilm formation. Metagenomic analyses of the biofilm
      community with the GeoChip revealed an extremely diverse community (gene
      richness, 23409; Shannon-Weiner index H, 9.55). Presence of EcO157 in the mixed
      biofilm resulted in a significant decrease in the community alpha-diversity (t
      test, P<0.05), indicating a putative competition between the pathogen and
      indigenous spinach microbes. The decrease in the beta-diversity of the EcO157
      inoculated biofilm at 48 h (ANOVA, P<0.05) suggested a convergent shift in
      functional composition in response to EcO157 invasion. The success of EcO157 in
      the mixed biofilm is likely associated with its metabolic potential in utilizing
      spinach nutrients: the generation time of EcO157 in spinach lysates at 28 degrees
      C is ~ 38 min, which is comparable to that in rich broth. The significant
      decrease in the abundance of many genes involved in carbon, nitrogen, and
      phosphorus cycling in the EcO157-inoculated biofilms (t test, P<0.05) further
      support our conclusion that competition for essential macronutrients is likely
      the primary interaction between the EcO157 and indigenous spinach-biofilm
      species.

PMID- 22957053
TI  - Specificity determinants of the silkworm moth sex pheromone.
AB  - The insect olfactory system, particularly the peripheral sensory system for sex
      pheromone reception in male moths, is highly selective, but specificity
      determinants at the receptor level are hitherto unknown. Using the Xenopus oocyte
      recording system, we conducted a thorough structure-activity relationship study
      with the sex pheromone receptor of the silkworm moth, Bombyx mori, BmorOR1. When
      co-expressed with the obligatory odorant receptor co-receptor (BmorOrco), BmorOR1
      responded in a dose-dependent fashion to both bombykol and its related aldehyde,
      bombykal, but the threshold of the latter was about one order of magnitude
      higher. Solubilizing these ligands with a pheromone-binding protein (BmorPBP1)
      did not enhance selectivity. By contrast, both ligands were trapped by BmorPBP1
      leading to dramatically reduced responses. The silkworm moth pheromone receptor
      was highly selective towards the stereochemistry of the conjugated diene, with
      robust response to the natural (10E,12Z)-isomer and very little or no response to
      the other three isomers. Shifting the conjugated diene towards the functional
      group or elongating the carbon chain rendered these molecules completely
      inactive. In contrast, an analogue shortened by two omega carbons elicited the
      same or slightly higher responses than bombykol. Flexibility of the saturated C1
      C9 moiety is important for function as addition of a double or triple bond in
      position 4 led to reduced responses. The ligand is hypothesized to be
      accommodated by a large hydrophobic cavity within the helical bundle of
      transmembrane domains.

PMID- 22957054
TI  - Physiological integration ameliorates negative effects of drought stress in the
      clonal herb Fragaria orientalis.
AB  - Clonal growth allows plants to spread horizontally and to establish ramets in
      sites of contrasting resource status. If ramets remain physiologically
      integrated, clones in heterogeneous environments can act as cooperative systems-
      effects of stress on one ramet can be ameliorated by another connected ramet
      inhabiting benign conditions. But little is known about the effects of patch
      contrast on physiological integration of clonal plants and no study has addressed
      its effects on physiological traits like osmolytes, reactive oxygen intermediates
      and antioxidant enzymes. We examined the effect of physiological integration on
      survival, growth and stress indicators such as osmolytes, reactive oxygen
      intermediates (ROIs) and antioxidant enzymes in a clonal plant, Fragaria
      orientalis, growing in homogenous and heterogeneous environments differing in
      patch contrast of water availability (1 homogeneous (no contrast) group; 2 low
      contrast group; 3 high contrast group). Drought stress markedly reduced the
      survival and growth of the severed ramets of F. orientalis, especially in high
      contrast treatments. Support from a ramet growing in benign patch considerably
      reduced drought stress and enhanced growth of ramets in dry patches. The larger
      the contrast between water availability, the larger the amount of support the
      depending ramet received from the supporting one. This support strongly affected
      the growth of the supporting ramet, but not to an extent to cause increase in
      stress indicators. We also found indication of costs related to maintenance of
      physiological connection between ramets. Thus, the net benefit of physiological
      integration depends on the environment and integration between ramets of F.
      orientalis could be advantageous only in heterogeneous conditions with a high
      contrast.

PMID- 22957055
TI  - Macroalgae decrease growth and alter microbial community structure of the reef
      building coral, Porites astreoides.
AB  - With the continued and unprecedented decline of coral reefs worldwide, evaluating
      the factors that contribute to coral demise is of critical importance. As coral
      cover declines, macroalgae are becoming more common on tropical reefs.
      Interactions between these macroalgae and corals may alter the coral microbiome,
      which is thought to play an important role in colony health and survival.
      Together, such changes in benthic macroalgae and in the coral microbiome may
      result in a feedback mechanism that contributes to additional coral cover loss.
      To determine if macroalgae alter the coral microbiome, we conducted a field-based
      experiment in which the coral Porites astreoides was placed in competition with
      five species of macroalgae. Macroalgal contact increased variance in the coral
      associated microbial community, and two algal species significantly altered
      microbial community composition. All macroalgae caused the disappearance of a
      gamma-proteobacterium previously hypothesized to be an important mutualist of P.
      astreoides. Macroalgal contact also triggered: 1) increases or 2) decreases in
      microbial taxa already present in corals, 3) establishment of new taxa to the
      coral microbiome, and 4) vectoring and growth of microbial taxa from the
      macroalgae to the coral. Furthermore, macroalgal competition decreased coral
      growth rates by an average of 36.8%. Overall, this study found that competition
      between corals and certain species of macroalgae leads to an altered coral
      microbiome, providing a potential mechanism by which macroalgae-coral
      interactions reduce coral health and lead to coral loss on impacted reefs.

PMID- 22957056
TI  - Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non
      small cell lung cancer cells.
AB  - Histone deacetylase inhibitors (HDACi) are promising therapeutic agents which are
      currently used in combination with chemotherapeutic agents in clinical trials for
      cancer treatment including non-small cell lung cancer (NSCLC). However, the
      mechanisms underlying their anti-tumor activities remain elusive. Previous
      studies showed that inhibition of HDAC6 induces DNA damage and sensitizes
      transformed cells to anti-tumor agents such as etoposide and doxorubicin. Here,
      we showed that depletion of HDAC6 in two NSCLC cell lines, H292 and A549,
      sensitized cells to cisplatin, one of the first-line chemotherapeutic agents used
      to treat NSCLC. We suggested that depletion of HDAC6 increased cisplatin-induced
      cytotoxicity was due to the enhancement of apoptosis via activating ATR/Chk1
      pathway. Furthermore, we showed that HDAC6 protein levels were positively
      correlated with cisplatin IC(50) in 15 NSCLC cell lines. Lastly, depletion of
      HDAC6 in H292 xenografts rendered decreased tumor weight and volume and exhibited
      increased basal apoptosis compared with the controls in a xenograft mouse model.
      In summary, our findings suggest that HDAC6 is positively associated with
      cisplatin resistance in NSCLC and reveal HDAC6 as a potential novel therapeutic
      target for platinum refractory NSCLC.

PMID- 22957057
TI  - Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core"
      pathogenesis of disease.
AB  - The cause of psoriasis, a common chronic inflammatory skin disease, is not fully
      understood. Microarray experiments have been widely used in recent years to
      identify genes associated with psoriasis pathology, by comparing expression
      levels of lesional (LS) with adjacent non-lesional (NL) skin. It is commonly
      observed that the differentially expressed genes (DEGs) differ greatly across
      experiments, due to variations introduced in the microarray experiment pipeline.
      Therefore, a statistically based meta-analytic approach, which combines the
      results of individual studies, is warranted. In this study, a meta-analysis was
      conducted on 5 microarray data sets, including 193 LS and NL pairs. We termed
      this the Meta-Analysis Derived (MAD) transcriptome. In "MAD-5" transcriptome, 677
      genes were up-regulated and 443 were down-regulated in LS skin compared to NL
      skin. This represents a much larger set than the intersection of DEGs of these 5
      studies, which consisted of 100 DEGs. We also analyzed 3 of the studies conducted
      on the Affymetrix hgu133plus2 chips and found a greater number of DEGs (1084 up-
      and 748 down-regulated). Top canonical pathways over-represented in the MAD
      transcriptome include Atherosclerosis Signaling and Fatty Acid Metabolism, while
      several "new" genes identified are involved in Cardiovascular Development and
      Lipid Metabolism. These findings highlight the relationship between psoriasis and
      systemic manifestations such as the metabolic syndrome and cardiovascular
      disease. Then, the Meta Threshold Gradient Descent Regularization (MTGDR)
      algorithm was used to select potential markers distinguishing LS and NL skin. The
      resulting set (20 genes) contained many genes that were part of the residual
      disease genomic profile (RDGP) or "molecular scar" after successful treatment,
      and also genes subject to differential methylation in LS tissues. To conclude,
      this MAD transcriptome yielded a reference list of reliable psoriasis DEGs, and
      represents a robust pool of candidates for further discovery of pathogenesis and
      treatment evaluation.

PMID- 22957058
TI  - Insights into phosphate cooperativity and influence of substrate modifications on
      binding and catalysis of hexameric purine nucleoside phosphorylases.
AB  - The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233)
      displays great potential to produce nucleoside analogues in industry and can be
      exploited in the development of new anti-tumor gene therapies. In order to
      provide structural basis for enzyme and substrates rational optimization, aiming
      at those applications, the present work shows a thorough and detailed structural
      description of the binding mode of substrates and nucleoside analogues to the
      active site of the hexameric BsPNP233. Here we report the crystal structure of
      BsPNP233 in the apo form and in complex with 11 ligands, including clinically
      relevant compounds. The crystal structure of six ligands (adenine,
      2'deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine) in
      complex with a hexameric PNP are presented for the first time. Our data showed
      that free bases adopt alternative conformations in the BsPNP233 active site and
      indicated that binding of the co-substrate (2'deoxy)ribose 1-phosphate might
      contribute for stabilizing the bases in a favorable orientation for catalysis.
      The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5'
      hydroxyl group of adenosine and Arg(43*) side chain contributes for the ribosyl
      radical to adopt an unusual C3'-endo conformation. The structures with 6
      chloroguanosine and 8-bromoguanosine pointed out that the Cl(6) and Br(8)
      substrate modifications seem to be detrimental for catalysis and can be explored
      in the design of inhibitors for hexameric PNPs from pathogens. Our data also
      corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin
      and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for
      hexameric PNPs than aciclovir. Furthermore, comparative structural analyses
      indicated that the replacement of Ser(90) by a threonine in the B. cereus
      hexameric adenosine phosphorylase (Thr(91)) is responsible for the lack of
      negative cooperativity of phosphate binding in this enzyme.

PMID- 22957059
TI  - Genome-wide association study identified CNP12587 region underlying height
      variation in Chinese females.
AB  - INTRODUCTION: Human height is a highly heritable trait considered as an important
      factor for health. There has been limited success in identifying the genetic
      factors underlying height variation. We aim to identify sequence variants
      associated with adult height by a genome-wide association study of copy number
      variants (CNVs) in Chinese. METHODS: Genome-wide CNV association analyses were
      conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height
      variation, respectively. Height was measured with a stadiometer. Affymetrix
      SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs).
      We constructed a genomic map containing 1,009 CNPs in Chinese individuals and
      performed a genome-wide association study of CNPs with height. RESULTS: We
      detected 10 significant association signals for height (p<0.05) in the whole
      population, 9 and 11 association signals for Chinese female and male population,
      respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p =
      2.41 * 10(-4)) was found to be significantly associated with height variation in
      Chinese females even after strict Bonferroni correction (p = 0.048). Confirmatory
      real time PCR experiments lent further support for CNV validation. Compared to
      female subjects with two copies of the CNP, carriers of three copies had an
      average of 8.1% decrease in height. An important candidate gene, ubiquitin
      protein ligase NEDD4-like (NEDD4L), was detected at this region, which plays
      important roles in bone metabolism by binding to bone formation regulators.
      CONCLUSIONS: Our findings suggest the important genetic variants underlying
      height variation in Chinese.

PMID- 22957060
TI  - Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce
      retinal and cardiac pathology in Drosophila.
AB  - Mitochondrial fusion is essential to organelle homeostasis and organ health.
      Inexplicably, loss of function mutations of mitofusin 2 (Mfn2) specifically
      affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT) and
      atypical optic atrophy. As CMT-linked Mfn2 mutations are predominantly within the
      GTPase domain, we postulated that Mfn2 mutations in other functional domains
      might affect non-neurological tissues. Here, we defined in vitro and in vivo
      consequences of rare human mutations in the poorly characterized Mfn2 HR1 domain.
      Human exome sequencing data identified 4 rare non-synonymous Mfn2 HR1 domain
      mutations, two bioinformatically predicted as damaging. Recombinant expression of
      these (Mfn2 M393I and R400Q) in Mfn2-null murine embryonic fibroblasts (MEFs)
      revealed incomplete rescue of characteristic mitochondrial fragmentation,
      compared to wild-type human Mfn2 (hMfn2); Mfn2 400Q uniquely induced
      mitochondrial fragmentation in normal MEFs. To compare Mfn2 mutation effects in
      neurological and non-neurological tissues in vivo, hMfn2 and the two mutants were
      expressed in Drosophila eyes or heart tubes made deficient in endogenous fly
      mitofusin (dMfn) through organ-specific RNAi expression. The two mutants induced
      similar Drosophila eye phenotypes: small eyes and an inability to rescue the eye
      pathology induced by suppression of dMfn. In contrast, Mfn2 400Q induced more
      severe cardiomyocyte mitochondrial fragmentation and cardiac phenotypes than Mfn2
      393I, including heart tube dilation, depressed fractional shortening, and
      progressively impaired negative geotaxis. These data reveal a central functional
      role for Mfn2 HR1 domains, describe organ-specific effects of two Mfn2 HR1
      mutations, and strongly support prospective studies of Mfn2 400Q in heritable
      human heart disease of unknown genetic etiology.

PMID- 22957061
TI  - Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and
      herceptin-resistant breast cancer.
AB  - Alternative survival pathways are commonly seen to be upregulated upon inhibition
      of receptor tyrosine kinases (RTK), including Her-2. It is established that
      treatment with Herceptin leads to selective overexpression and activation of
      epidermal growth factor receptor (EGFR) and Src which further contributes to
      oncogenesis in Herceptin resistant and triple negative breast cancer (TNBC)
      patients. Here, we show a co-regulated upregulation in the expression of Annexin
      A2 (AnxA2), a known substrate of Src and one of the regulators of EGFR receptor
      endocytosis, in Herceptin resistant and Her-2 negative breast cancer.
      Immunohistochemical expression analysis revealed a reciprocal regulation between
      Her-2 and AnxA2 in breast cancer clinical samples as well as in cell lines as
      confirmed by protein and RNA analysis. The siRNA and Herceptin mediated
      downregulation/inhibition of Her-2 in Her-2 amplified cells induced AnxA2
      expression and membrane translocation. In this study we report a possible
      involvement of AnxA2 in maintaining constitutively activated EGFR downstream
      signaling intermediates and hence in cell proliferation, migration and viability.
      This effect was consistent in Herceptin resistant JIMT-1 cells as well as in Her
      2 negative breast cancer. The siRNA mediated AnxA2 downregulation leads to
      increased apoptosis, decreased cell viability and migration. Our studies further
      indicate the role of AnxA2 in EGFR-Src membrane bound signaling complex and
      ligand induced activation of downstream signaling pathways. Targeting this AnxA2
      dependent positive regulation of EGFR signaling cascade may be of therapeutic
      value in Her-2 negative breast cancer.

PMID- 22957062
TI  - Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts
      chemoresistance through inactivation of Src and Bcr-Abl proteins.
AB  - The development of multidrug resistance (MDR) limits the efficacy of continuous
      chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular
      weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers
      and has been associated to poor prognosis. This prompted us to investigate the
      involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP
      in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is
      highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells,
      the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted
      chemoresistance to vincristine and imatinib mesylate, followed by a decrease of
      Src and Bcr-Abl phosphorylation at the activating sites, inactivating both
      kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to
      chemoresistance to vincristine. Our findings describe, for the first time, that
      LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src
      and Bcr-Abl kinases in more active statuses. These findings suggest that
      inhibition of LMW-PTP may be a useful strategy for the development of therapies
      for multidrug resistant CML.

PMID- 22957064
TI  - Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for
      intestinal inflammation.
AB  - Inflammation has classically been defined histopathologically, especially by the
      presence of immune cell infiltrates. However, more recent studies suggest a role
      for "low-grade" inflammation in a variety of disorders ranging from metabolic
      syndrome to cancer, which is defined by modest elevations in pro-inflammatory
      gene expression. Consequently, there is a need for cost-effective, non-invasive
      biomarkers that, ideally, would have the sensitivity to detect low-grade
      inflammation and have a dynamic range broad enough to reflect classic robust
      intestinal inflammation. Herein, we report that, for assessment of intestinal
      inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose.
      Specifically, using a well-characterized mouse model of DSS colitis, we observed
      that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL
      1beta, CXCL1, TNFalpha) are modestly but significantly induced by very low
      concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher
      concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic
      analysis noted only modest immune infiltrates at low DSS concentration and robust
      colitis at higher DSS concentrations. In accordance, increased levels of the
      neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and
      4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis
      development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR,
      the assay of fecal Lcn-2 requires only a stool sample, permits measurement over
      time, and can detect inflammation as early as 1 day following DSS administration.
      Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive,
      dynamic, stable and cost-effective means to monitor intestinal inflammation in
      mice.

PMID- 22957063
TI  - Prediction of conserved precursors of miRNAs and their mature forms by
      integrating position-specific structural features.
AB  - MicroRNA (miRNA) precursor hairpins have a unique secondary structure, nucleotide
      length, and nucleotide content that are in most cases evolutionarily conserved.
      The aim of this study was to utilize position-specific features of miRNA hairpins
      to improve their identification. To this end, we defined the evolutionary and
      structurally conserved features in each position of miRNA hairpins with
      heuristically derived values, which were successfully integrated using a
      probabilistic framework. Our method, miRRim2, can not only accurately detect
      miRNA hairpins, but infer the location of a mature miRNA sequence. To evaluate
      the accuracy of miRRim2, we designed a cross validation test in which the whole
      human genome was used for evaluation. miRRim2 could more accurately detect miRNA
      hairpins than the other computational predictions that had been performed on the
      human genome, and detect the position of the 5'-end of mature miRNAs with
      sensitivity and positive predictive value (PPV) above 0.4. To further evaluate
      miRRim2 on independent data, we applied it to the Ciona intestinalis genome. Our
      method detected 47 known miRNA hairpins among top 115 candidates, and pinpointed
      the 5'-end of mature miRNAs with sensitivity and PPV about 0.4. When our results
      were compared with deep-sequencing reads of small RNA libraries from Ciona
      intestinalis cells, we found several candidates in which the predicted mature
      miRNAs were in good accordance with deep-sequencing results.

PMID- 22957065
TI  - Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a
      meta-analysis based on Chinese adults.
AB  - BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common
      pathological type for nephrotic syndrome in adults in western countries and
      China. The benefits and harms of immunosuppressive treatment in IMN remain
      controversial. OBJECTIVES: To assess the efficacy and safety of different
      immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.
      METHODS: PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang,
      were searched for relevant studies published before December 2011. Reference
      lists of nephrology textbooks, review articles were checked. A meta-analysis of
      randomized controlled trials (RCTs) meeting the criteria was performed using
      Review Manager. MAIN RESULTS: 17 studies were included, involving 696 patients.
      Calcineurin inhibitors had a better effect when compared to alkylating agents, on
      complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete
      remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer
      side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown
      statistical significance in inducing more remissions. When compared to
      cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect,
      mycophenolate mofetil (MMF) showed significant beneficial on effectiveness
      (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete
      remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15). CONCLUSIONS: This
      analysis based on Chinese adults and short duration RCTs suggested calcineurin
      inhibitors, especially TAC, were more effective in proteinuria reduction in IMN
      with acceptable side effects. Long duration RCTs were needed to confirm the long
      term effects of those agents in nephrotic IMN.

PMID- 22957066
TI  - Functional gene polymorphisms in the serotonin system and traumatic life events
      modulate the neural basis of fear acquisition and extinction.
AB  - Fear acquisition and extinction are crucial mechanisms in the etiology and
      maintenance of anxiety disorders. Moreover, they might play a pivotal role in
      conveying the influence of genetic and environmental factors on the development
      of a (more or less) stronger proneness for, or resilience against
      psychopathology. There are only few insights in the neurobiology of genetically
      and environmentally based individual differences in fear learning and extinction.
      In this functional magnetic resonance imaging study, 74 healthy subjects were
      investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. L(A)L(A);
      triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was
      to investigate the influence of genetic factors and traumatic life events on skin
      conductance responses (SCRs) and neural responses (amygdala, insula, dorsal
      anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC))
      during acquisition and extinction learning in a differential fear conditioning
      paradigm. Fear acquisition was characterized by stronger late conditioned and
      unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During
      extinction traumatic life events were associated with reduced amygdala activation
      in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2
      (G(-703)T) polymorphism with a higher number of traumatic life events showed
      enhanced responsiveness in the amygdala during acquisition and in the vmPFC
      during extinction learning compared with non-carriers. Finally, a combined effect
      of the two polymorphisms with higher responses in S- and T-allele carriers was
      found in the dACC during extinction. The results indicate an increased expression
      of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S
      allele carriers. A combined effect of the two polymorphisms on dACC activation
      during extinction might be associated with prolonged fear expression. Gene-by
      environment interactions in amygdala and vmPFC activation may reflect a neural
      endophenotype translating genetic and adverse environmental influences into
      vulnerability for or resilience against developing affective psychopathology.

PMID- 22957067
TI  - A method for quantifying consistency in animal distributions using survey data.
AB  - The degree of consistency with which groups of animals use the landscape is
      determined by a variety of ecological processes that influence their movements
      and patterns of habitat use. We developed a technique termed Distributional
      Consistency that uses survey data of unmarked individuals to quantify temporal
      consistency in their spatial distribution, while accounting for changes in
      population size. Distributional consistency is quantified by comparing the
      observed distribution patterns to all theoretically possible distribution
      patterns of observed individuals, leading to a proportional score between 0 and
      1, reflecting increasingly consistent use of sites within a region. The technique
      can be applied to survey data for any taxa across a range of spatial and temporal
      scales. We suggest ways in which distributional consistency could provide
      inferences about the dispersal and habitat decisions of individuals, and the
      scales at which these decisions operate. Distributional consistency integrates
      spatial and temporal processes to quantify an important characteristic of
      different habitats and their use by populations, which in turn will be
      particularly useful in complimenting and interpreting other ecological measures
      such as population density and stability. The technique can be applied to many
      existing data sets to investigate and evaluate a range of important ecological
      questions using simple survey data.

PMID- 22957068
TI  - Objective fidelity evaluation in multisensory virtual environments: auditory cue
      fidelity in flight simulation.
AB  - We argue that objective fidelity evaluation of virtual environments, such as
      flight simulation, should be human-performance-centred and task-specific rather
      than measure the match between simulation and physical reality. We show how
      principled experimental paradigms and behavioural models to quantify human
      performance in simulated environments that have emerged from research in
      multisensory perception provide a framework for the objective evaluation of the
      contribution of individual cues to human performance measures of fidelity. We
      present three examples in a flight simulation environment as a case study:
      Experiment 1: Detection and categorisation of auditory and kinematic motion cues;
      Experiment 2: Performance evaluation in a target-tracking task; Experiment 3:
      Transferrable learning of auditory motion cues. We show how the contribution of
      individual cues to human performance can be robustly evaluated for each task and
      that the contribution is highly task dependent. The same auditory cues that can
      be discriminated and are optimally integrated in experiment 1, do not contribute
      to target-tracking performance in an in-flight refuelling simulation without
      training, experiment 2. In experiment 3, however, we demonstrate that the
      auditory cue leads to significant, transferrable, performance improvements with
      training. We conclude that objective fidelity evaluation requires a task-specific
      analysis of the contribution of individual cues.

PMID- 22957069
TI  - The clinical characteristics and direct medical cost of influenza in hospitalized
      children: a five-year retrospective study in Suzhou, China.
AB  - BACKGROUND: There have been few studies on children hospitalized with influenza
      published from mainland China. We performed a retrospective review of medical
      charts to describe the epidemiology, clinical features and direct medical cost of
      laboratory-proven influenza hospitalized children in Suzhou, China. METHODS:
      Retrospective study on children with documented influenza infection hospitalized
      at Suzhou Children Hospital during 2005-2009 was conducted using a structured
      chart review instrument. RESULTS: A total of 480 children were positive by immuno
      fluorescent assay for influenza during 2005-2009. The hospitalizations for
      influenza occurred in 8-12 months of the year, most commonly in the winter with a
      second late summer peak (August-September). Influenza A accounted for 86.3%, and
      of these 286 (59.6%) were male, and 87.2% were <5 years of age. The median length
      of hospital stay was 7 days. Fever was the most common symptom, occurring in 398
      (82.9%) children. There were 394 (82.1%) children with pneumonia and 70.2% of
      these hospitalized children had radiographic evidence of a pulmonary infiltrate.
      One hundred and twelve children (23.3%) required oxygen treatments and 13 (2.7%)
      were transferred to the ICU. Multivariable logistic regression showed that
      compared with the <= 6 months children, those aged >60 months old had shorter
      hospital stay (OR = 0.45); children with oxygen treatment tended to have longer
      hospital stays than those without oxygen treatment (OR = 2.14). The mean cost of
      each influenza-related hospitalization was US$ 624 (US$ 1323 for children
      referred to ICU and US$ 617 for those cared for on the wards). High risk children
      had higher total cost than low-risk patients. CONCLUSION: Compared to other
      countries, in Suzhou, children hospitalized with influenza have longer hospital
      stay and higher percentage of pneumonia. The direct medical cost is high relative
      to family income. Effective strategies of influenza immunization of young
      children in China may be beneficial in addressing this disease burden.

PMID- 22957070
TI  - Kinetics of T helper subsets and associated cytokines correlate well with the
      clinical activity of graft-versus-host disease.
AB  - BACKGROUND: CD4(+)interferon (IFN)-gamma(+) T cell (Th1) and CD4(+)interleukin
      (IL)-4(+) T cell (Th2) polarizations are crucial in the pathogenesis of graft
      versus-host disease (GVHD). However, this hypothesis is largely based on animal
      experiments of Parent-into-F1 GVHD model. The causal relationship between
      kinetics of Th1, Th2 and associated cytokines and the clinical activity of GVHD
      in a real world situation remains unknown. METHODOLOGY: Peripheral blood was
      collected every week prospectively from Day 0 to Day 210 (patients without GVHD)
      or Day 300 (patients with chronic GVHD) after allogeneic peripheral blood stem
      cell transplantation in consecutive 27 patients. The frequencies of Th1 and Th2
      within CD4(+) T cells were determined by flow cytometry and pplasma IFN-gamma, IL
      12, IL-4, and IL-10 were determined by ELISA. PRINCIPAL FINDINGS: Kinetics of
      Th1, Th2 frequency, and the plasma IL-10 and IFN-gamma more commonly coincided
      with, rather than predicted, the activity of GVHD. These markers are
      significantly higher when acute or chronic GVHD developed. The kinetics of IL-10
      is especially correlated well with the activity of GVHD during clinical course of
      immunosuppressive treatment. For patients with hepatic GVHD, there is a positive
      correlation between plasma IL-10 levels and the severity of hepatic injury. The
      frequency of Th2 is also significant higher in acute GVHD and tends to be higher
      in chronic GVHD. Interestingly, there is a very good positive correlation between
      the frequency of Th1 and Th2 (r = 0.951, p<0.001). The plasma level of IL-4 and
      IL-12 are not associated with the activity of GVHD. CONCLUSIONS: The frequency of
      Th1, Th2 within CD4(+) T cells and plasma IL-10 and IFN-gamma are good biomarkers
      of GVHD. Plasma IL-10 can also be used to monitor the therapeutic responsiveness.
      Furthermore, both Th1 and Th2 likely contribute to the pathogenesis of GVHD.

PMID- 22957071
TI  - Mind wandering in Chinese daily lives--an experience sampling study.
AB  - Mind wandering has recently received extensive research because it reveals an
      important characteristic of our consciousness: conscious experience can arise
      internally and involuntarily. As the first attempt to examine mind wandering in a
      non-western population, the present study used experience-sampling method to
      collect the daily momentary mind wandering episodes in a Chinese sample. The
      results showed that mind wandering was also a ubiquitous experience among the
      Chinese population, and, instead of emerging out of nowhere, it was often
      elicited by external or internal cues. Furthermore, most of the mind wandering
      episodes involved prospective thinking and were closely related to one's personal
      life. Finally, the frequency of mind wandering was influenced by some contextual
      factors. These results taken together suggest that mind wandering plays an
      important role in helping people to maintain a continuous feeling of "self" and
      to prepare them to cope with the upcoming events.

PMID- 22957072
TI  - Live imaging of mouse endogenous neural progenitors migrating in response to an
      induced tumor.
AB  - Adult neurogenesis is restricted to specific brain regions. Although involved in
      the continuous supply of interneurons for the olfactory function, the role of
      neural precursors in brain damage-repair remains an open question. Aiming to in
      vivo identify endogenous neural precursor cells migrating towards a brain damage
      site, the monoclonal antibody Nilo2 recognizing cell surface antigens on
      neuroblasts, was coupled to magnetic glyconanoparticles (mGNPs). The Nilo2-mGNP
      complexes allowed, by magnetic resonance imaging in living animals, the in vivo
      identification of endogenous neural precursors at their niche, as well as their
      migration to a lesion site (induced brain tumor), which was fast (within hours)
      and orderly. Interestingly, the rapid migration of neuroblasts towards a damage
      site is a characteristic that might be exploited to precisely localize early
      damage events in neurodegenerative diseases. In addition, it might facilitate the
      study of regenerative mechanisms through the activation of endogenous neural cell
      precursors. A similar approach, combining magnetic glyconanoparticles linked to
      appropriate antibodies could be applied to flag other small cell subpopulations
      within the organism, track their migration, localize stem cell niches, cancer
      stem cells or even track metastatic cells.

PMID- 22957073
TI  - Remarkable changes in behavior and physiology of laboratory mice after the
      massive 2011 Tohoku earthquake in Japan.
AB  - A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by
      several long and intense aftershocks. Laboratory mice housed in the Tokyo,
      located approximately 330 km south of this earthquake's epicenter, displayed
      remarkable changes in a variety of behaviors and physiological measures. Although
      unusual pre-earthquake behaviors have been previously reported in laboratory
      animals, little is known about behavioral and physiological changes that occur
      after a great earthquake. In the present study, the effects of Tohoku earthquake
      on mice behavior were investigated. "Earthquake-experienced" mice displayed a
      marked increase in food consumption without gaining body weight in response to
      the earthquake. They also displayed enhanced anxiety, and in a formal fear memory
      task, showed significantly greater tone- and context-dependent conditioned
      freezing. Water maze performance of earthquake-experienced mice showed the
      quicker acquisition of the task, faster swim speed and longer swim distance than
      the naive mice. Serum corticosterone levels were elevated compared to the naive
      mice, indicating that the earthquake and aftershocks were stressful for the mice.
      These results demonstrate that great earthquakes strongly affect mouse behaviors
      and physiology. Although the effects of a variety of experimental manipulations
      on mouse behaviors in disease models or in models of higher cognitive functions
      have been extensively examined, researchers need to be aware how natural
      phenomena, such as earthquakes and perhaps other natural environmental factors,
      influence laboratory animal behaviors and physiology.

PMID- 22957074
TI  - Cilostazol prevents endothelin-induced smooth muscle constriction and
      proliferation.
AB  - Cilostazol is a phosphodiesterase inhibitor that has been shown to inhibit
      platelet activation. Endothelin is known to be the most potent endogenous growth
      promoting and vasoactive peptide. In patients and animal models with stroke, the
      level of circulating endothelin increases and complicates the recovery progress
      contributed by vascular constriction (an immediate pathology) and vascular
      proliferation (a long-term pathology). However, the effects of cilostazol on
      endothelin have not been explored. To demonstrate the dual-antagonizing effects
      of cilostazol on vasoconstriction and cell proliferation induced by endothelin,
      we used primary culture of mouse vascular smooth muscle cells in vitro, mouse
      femoral artery ex vivo, and intracranial basilar artery ex vivo. We show that the
      dual-inhibition effects of cilostazol are mediated by blocking endothelin-induced
      extracellular calcium influx. Although cilostazol does not inhibit endothelin
      induced intraorganellar calcium release, blockade of extracellular calcium influx
      is sufficient to blunt endothelin-induced vasoconstriction. We also show that
      cilostazol inhibits endothelin-induced cellular proliferation by blocking
      extracellular calcium influx. Inhibition of cAMP-dependent protein kinase (PKA)
      can block anti-proliferation activity of cilostazol, confirming the downstream
      role of PKA in cellular proliferation. To further demonstrate the selectivity of
      the dual-antagonizing effects of cilostazol, we used a different
      phosphodiesterase inhibitor. Interestingly, sildenafil inhibits endothelin
      induced vasoconstriction but not cellular proliferation in smooth muscle cells.
      For the first time, we show selective dual-antagonizing effects of cilostazol on
      endothelin. We propose that cilostazol is an excellent candidate to treat
      endothelin-associated diseases, such as stroke.

PMID- 22957075
TI  - Functional PstI/RsaI polymorphism in CYP2E1 is associated with the development,
      progression and poor outcome of gastric cancer.
AB  - BACKGROUND: Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been
      shown to metabolically activate various carcinogens, which is critical for the
      development and progression of cancers. It has demonstrated that CYP2E1
      polymorphisms alter the transcriptional activity of the gene. However, studies on
      the association between CYP2E1 polymorphisms (PstI/RsaI or DraI) and gastric
      cancer have reported conflicting results. Thus, the aim of the present study was
      to investigate whether CYP2E1 polymorphisms is associated with the development
      and progression of gastric cancer and its prognosis in Chinese patients. METHODS:
      A case-control study was conducted in which CYP2E1 PstI/RsaI and DraI
      polymorphisms were analyzed in 510 Chinese patients with gastric cancer and 510
      age- and sex- matched healthy controls by PCR-RFLP. Odds ratios were estimated by
      multivariate logistic regression, and the lifetime was calculated by Kaplan-Meier
      survival curves. In addition, a meta-analysis was also conducted to verify the
      findings. RESULTS: For CYP2E1 PstI/RsaI polymorphism, C2C2 homozygotes (OR =
      2.15; CI: 1.18-3.94) and C2 carriers (OR = 1.48; CI: 1.13-1.96) were associated
      with an increased risk of gastric cancer when compared with C1C1 homozygotes.
      Both C1C2 and C2C2 genotypes were associated with advanced stage, but not the
      grade of gastric cancer. Moreover, C2C2 genotype was identified as an independent
      marker of poor overall survival for gastric cancer. However, there was not any
      significant association between CYP2E1 DraI polymorphism and the risk of gastric
      cancer. In the meta-analysis, pooled data from 13 studies confirmed that the
      CYP2E1 PstI/RsaI polymorphism was associated with a significantly increased risk
      of gastric cancer. CONCLUSION: CYP2E1 PstI/RsaI polymorphism is associated with
      increased risk of development, progression and poor prognosis of gastric cancer
      in Chinese patients. Pooled data from 13 studies, mainly in Asian countries, are
      in agreement with our findings.

PMID- 22957076
TI  - Genetic diversity, population structure and linkage disequilibrium in elite
      Chinese winter wheat investigated with SSR markers.
AB  - To ascertain genetic diversity, population structure and linkage disequilibrium
      (LD) among a representative collection of Chinese winter wheat cultivars and
      lines, 90 winter wheat accessions were analyzed with 269 SSR markers distributed
      throughout the wheat genome. A total of 1,358 alleles were detected, with 2 to 10
      alleles per locus and a mean genetic richness of 5.05. The average genetic
      diversity index was 0.60, with values ranging from 0.05 to 0.86. Of the three
      genomes of wheat, ANOVA revealed that the B genome had the highest genetic
      diversity (0.63) and the D genome the lowest (0.56); significant differences were
      observed between these two genomes (P<0.01). The 90 Chinese winter wheat
      accessions could be divided into three subgroups based on STRUCTURE, UPGMA
      cluster and principal coordinate analyses. The population structure derived from
      STRUCTURE clustering was positively correlated to some extent with geographic eco
      type. LD analysis revealed that there was a shorter LD decay distance in Chinese
      winter wheat compared with other wheat germplasm collections. The maximum LD
      decay distance, estimated by curvilinear regression, was 17.4 cM (r(2)>0.1), with
      a whole genome LD decay distance of approximately 2.2 cM (r(2)>0.1, P<0.001).
      Evidence from genetic diversity analyses suggest that wheat germplasm from other
      countries should be introduced into Chinese winter wheat and distant
      hybridization should be adopted to create new wheat germplasm with increased
      genetic diversity. The results of this study should provide valuable information
      for future association mapping using this Chinese winter wheat collection.

PMID- 22957077
TI  - Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization
      dependent mechanism.
AB  - The phenolic phytoalexin resveratrol is well known for its health-promoting and
      anticancer properties. Its potential benefits are, however, limited due to its
      low bioavailability. Pterostilbene, a natural dimethoxylated analog of
      resveratrol, presents higher anticancer activity than resveratrol. The mechanisms
      by which this polyphenol acts against cancer cells are, however, unclear. Here,
      we show that pterostilbene effectively inhibits cancer cell growth and stimulates
      apoptosis and autophagosome accumulation in cancer cells of various origins.
      However, these mechanisms are not determinant in cell demise. Pterostilbene
      promotes cancer cell death via a mechanism involving lysosomal membrane
      permeabilization. Different grades of susceptibility were observed among the
      different cancer cells depending on their lysosomal heat shock protein 70 (HSP70)
      content, a known stabilizer of lysosomal membranes. A375 melanoma and A549 lung
      cancer cells with low levels of HSP70 showed high susceptibility to
      pterostilbene, whereas HT29 colon and MCF7 breast cancer cells with higher levels
      of HSP70 were more resistant. Inhibition of HSP70 expression increased
      susceptibility of HT29 colon and MCF7 breast cancer cells to pterostilbene. Our
      data indicate that lysosomal membrane permeabilization is the main cell death
      pathway triggered by pterostilbene.

PMID- 22957078
TI  - A study on the dose distributions in various materials from an Ir-192 HDR
      brachytherapy source.
AB  - Dose distributions of (192)Ir HDR brachytherapy in phantoms simulating water,
      bone, lung tissue, water-lung and bone-lung interfaces using the Monte Carlo
      codes EGS4, FLUKA and MCNP4C are reported. Experiments were designed to gather
      point dose measurements to verify the Monte Carlo results using Gafchromic film,
      radiophotoluminescent glass dosimeter, solid water, bone, and lung phantom. The
      results for radial dose functions and anisotropy functions in solid water phantom
      were consistent with previously reported data (Williamson and Li). The radial
      dose functions in bone were affected more by depth than those in water. Dose
      differences between homogeneous solid water phantoms and solid water-lung
      interfaces ranged from 0.6% to 14.4%. The range between homogeneous bone phantoms
      and bone-lung interfaces was 4.1% to 15.7%. These results support the
      understanding in dose distribution differences in water, bone, lung, and their
      interfaces. Our conclusion is that clinical parameters did not provide dose
      calculation accuracy for different materials, thus suggesting that dose
      calculation of HDR treatment planning systems should take into account material
      density to improve overall treatment quality.

PMID- 22957079
TI  - Body mass index and the risk of dementia among Louisiana low income diabetic
      patients.
AB  - BACKGROUND: The association between obesity and dementia risk remains debatable
      and no studies have assessed this association among diabetic patients. The aim of
      our study was to investigate the association between body mass index (BMI) and
      dementia risk among middle and low income diabetic patients.
      METHODOLOGY/PRINCIPAL FINDINGS: The sample included 44,660 diabetic patients
      (19,618 white and 25,042 African American) 30 to 96 years of age without a
      history of dementia in the Louisiana State University Hospital-Based Longitudinal
      Study. During a mean follow-up period of 3.9 years, 388 subjects developed
      incident dementia. The age- and sex-adjusted hazards ratios (HRs) for incident
      dementia at different levels of BMI (<= 25, 25-26.9, 27-29.9, 30-34.9, and >= 35
      kg/m(2)) were 1.00, 0.53 (95% CI 0.34-0.83), 0.29 (0.18-0.45), 0.37 (0.25-0.56),
      and 0.31 (0.21-0.48) (P(trend)<0.001) in white diabetic patients, and 1.00, 1.00
      (95% CI 0.62-1.63), 0.62 (0.39-0.98), 0.56 (0.36-0.86), and 0.65 (0.43-1.01)
      (P(trend) = 0.029) in African American diabetic patients. Further adjustment for
      other confounding factors affected the results only slightly. There was a
      significant interaction between race and BMI on dementia risk (chi(2) = 5.52,
      1df, p<0.025), such that the association was stronger in white patients. In
      stratified analyses, the multivariate-adjusted inverse association between BMI
      and risk of dementia was present in subjects aged 55-64 years, 65-74 years, and
      >= 75 years, in men and women, in non-smokers and smokers, and in subjects with
      different types of health insurance. CONCLUSIONS/SIGNIFICANCE: Higher baseline
      BMI was associated with a lower risk of dementia among diabetic patients, and
      this association was stronger among white than among African American diabetic
      patients.

PMID- 22957080
TI  - Evolution of genes involved in gamete interaction: evidence for positive
      selection, duplications and losses in vertebrates.
AB  - Genes encoding proteins involved in sperm-egg interaction and fertilization
      exhibit a particularly fast evolution and may participate in prezygotic species
      isolation [1], [2]. Some of them (ZP3, ADAM1, ADAM2, ACR and CD9) have
      individually been shown to evolve under positive selection [3], [4], suggesting a
      role of positive Darwinian selection on sperm-egg interaction. However, the genes
      involved in this biological function have not been systematically and
      exhaustively studied with an evolutionary perspective, in particular across
      vertebrates with internal and external fertilization. Here we show that 33 genes
      among the 69 that have been experimentally shown to be involved in fertilization
      in at least one taxon in vertebrates are under positive selection. Moreover, we
      identified 17 pseudogenes and 39 genes that have at least one duplicate in one
      species. For 15 genes, we found neither positive selection, nor gene copies or
      pseudogenes. Genes of teleosts, especially genes involved in sperm-oolemma
      fusion, appear to be more frequently under positive selection than genes of birds
      and eutherians. In contrast, pseudogenization, gene loss and gene gain are more
      frequent in eutherians. Thus, each of the 19 studied vertebrate species exhibits
      a unique signature characterized by gene gain and loss, as well as position of
      amino acids under positive selection. Reflecting these clade-specific signatures,
      teleosts and eutherian mammals are recovered as clades in a parsimony analysis.
      Interestingly the same analysis places Xenopus apart from teleosts, with which it
      shares the primitive external fertilization, and locates it along with amniotes
      (which share internal fertilization), suggesting that external or internal
      environmental conditions of germ cell interaction may not be the unique factors
      that drive the evolution of fertilization genes. Our work should improve our
      understanding of the fertilization process and on the establishment of
      reproductive barriers, for example by offering new leads for experiments on genes
      identified as positively selected.

PMID- 22957081
TI  - Effect of birth year on birth weight and obesity in adulthood: comparison between
      subjects born prior to and during the great depression in Iceland.
AB  - BACKGROUND: Many epidemiological studies have linked small size at birth to
      adverse adult health outcomes but the relative influence of environmental
      exposures is less well established. METHODS: The authors investigated the impact
      of prenatal environmental exposure by comparing 2750 participants born before
      (1925-1929) and during (1930-1934) the Great Depression in Reykjavik, Iceland.
      Calendar year served as proxy for environmental effects. Anthropometric
      measurements at birth and school-age (8-13 years) were collected from national
      registries. Participants were medically examined as adults (33-65 years).
      RESULTS: Mean birth weight, adjusted for maternal age and parity, decreased by 97
      g (95% confidence interval (CI): 39, 156) for men and 70 g (95% CI: 11, 129) for
      women from 1925 to 1934; growth at school-age was significantly reduced for
      participants growing during the Depression. As adults, women prenatally exposed
      to the Depression had higher body mass index (Delta0.6 kg/m(2), 95% CI: 0.2,
      1.1), higher fasting blood glucose levels (Delta0.16 mmol/L, 95% CI: 0.07, 0.23)
      and greater odds of being obese 1.43 (95% CI: 1.01, 2.02) compared to unexposed
      counterparts. Non-significant associations were observed in men. CONCLUSION:
      Reduction in birth weight due to rapid shifts in the economic environment appears
      to have a modest but significant association with later obesity for women while
      male offspring appear to be less affected by these conditions.

PMID- 22957082
TI  - Genetic architecture of sexual selection: QTL mapping of male song and female
      receiver traits in an acoustic moth.
AB  - Models of indirect (genetic) benefits sexual selection predict linkage
      disequilibria between genes that influence male traits and female preferences,
      owing to non-random mate choice or physical linkage. Such linkage disequilibria
      can accelerate the evolution of traits and preferences to exaggerated levels.
      Both theory and recent empirical findings on species recognition suggest that
      such linkage disequilibria may result from physical linkage or pleiotropy, but
      very little work has addressed this possibility within the context of sexual
      selection. We studied the genetic architecture of sexually selected traits by
      analyzing signals and preferences in an acoustic moth, Achroia grisella, in which
      males attract females with a train of ultrasound pulses and females prefer loud
      songs and a fast pulse rhythm. Both male signal characters and female preferences
      are repeatable and heritable traits. Moreover, female choice is based largely on
      male song, while males do not appear to provide direct benefits at mating. Thus,
      some genetic correlation between song and preference traits is expected. We
      employed a standard crossing design between inbred lines and used AFLP markers to
      build a linkage map for this species and locate quantitative trait loci (QTL)
      that influence male song and female preference. Our analyses mostly revealed QTLs
      of moderate strength that influence various male signal and female receiver
      traits, but one QTL was found that exerts a major influence on the pulse-pair
      rate of male song, a critical trait in female attraction. However, we found no
      evidence of specific co-localization of QTLs influencing male signal and female
      receiver traits on the same linkage groups. This finding suggests that the sexual
      selection process would proceed at a modest rate in A. grisella and that
      evolution toward exaggerated character states may be tempered. We suggest that
      this equilibrium state may be more the norm than the exception among animal
      species.

PMID- 22957084
TI  - Declines in the lethality of suicide attempts explain the decline in suicide
      deaths in Australia.
AB  - BACKGROUND: To investigate the epidemiology of a steep decrease in the incidence
      of suicide deaths in Australia. METHODS: National data on suicide deaths and
      deliberate self-harm for the period 1994-2007 were obtained from the Australian
      Institute of Health and Welfare. We calculated attempt and death rates for five
      major methods and the lethality of these methods. Negative binomial regression
      was used to estimate the size and significance of method-specific time-trends in
      attempts and lethality. RESULTS: Hanging, motor vehicle exhaust and firearms were
      the most lethal methods, and together accounted for 72% of all deaths. The
      lethality of motor vehicle exhaust attempts decreased sharply (RR = 0.94 per
      year, 95% CI 0.93-0.95) while the motor vehicle exhaust attempt rate changed
      little; this combination of motor vehicle exhaust trends explained nearly half of
      the overall decline in suicide deaths. Hanging lethality also decreased sharply
      (RR = 0.96 per year, 95% CI 0.956-0.965) but large increases in hanging attempts
      negated the effect on death rates. Firearm lethality changed little while
      attempts decreased. CONCLUSION: Declines in the lethality of suicide attempts
      especially attempts by motor vehicle exhaust and hanging-explain the remarkable
      decline in deaths by suicide in Australia since 1997.

PMID- 22957083
TI  - An internal model architecture for novelty detection: implications for cerebellar
      and collicular roles in sensory processing.
AB  - The cerebellum is thought to implement internal models for sensory prediction,
      but details of the underlying circuitry are currently obscure. We therefore
      investigated a specific example of internal-model based sensory prediction,
      namely detection of whisker contacts during whisking. Inputs from the vibrissae
      in rats can be affected by signals generated by whisker movement, a phenomenon
      also observable in whisking robots. Robot novelty-detection can be improved by
      adaptive noise-cancellation, in which an adaptive filter learns a forward model
      of the whisker plant that allows the sensory effects of whisking to be predicted
      and thus subtracted from the noisy sensory input. However, the forward model only
      uses information from an efference copy of the whisking commands. Here we show
      that the addition of sensory information from the whiskers allows the adaptive
      filter to learn a more complex internal model that performs more robustly than
      the forward model, particularly when the whisking-induced interference has a
      periodic structure. We then propose a neural equivalent of the circuitry required
      for adaptive novelty-detection in the robot, in which the role of the adaptive
      filter is carried out by the cerebellum, with the comparison of its output (an
      estimate of the self-induced interference) and the original vibrissal signal
      occurring in the superior colliculus, a structure noted for its central role in
      novelty detection. This proposal makes a specific prediction concerning the
      whisker-related functions of a region in cerebellar cortical zone A(2) that in
      rats receives climbing fibre input from the superior colliculus (via the inferior
      olive). This region has not been observed in non-whisking animals such as cats
      and primates, and its functional role in vibrissal processing has hitherto
      remained mysterious. Further investigation of this system may throw light on how
      cerebellar-based internal models could be used in broader sensory, motor and
      cognitive contexts.

PMID- 22957085
TI  - A distinct role of the queen in coordinated workload and soil distribution in
      eusocial naked mole-rats.
AB  - We investigated how group members achieve collective decision-making, by
      considering individual intrinsic behavioural rules and behavioural mechanisms for
      maintaining social integration. Using a simulated burrow environment, we
      investigated the behavioural rules of coordinated workload for soil distribution
      in a eusocial mammal, the naked mole-rat (Heterocephalus glaber). We tested two
      predictions regarding a distinct role of the queen, a socially dominant
      individual in the caste system: the presence of a queen would increase the
      workload of other caste individuals, and the cues by a queen would affect the
      soil distribution. In experiment 1, we placed four individuals of various castes
      from the same colony into an experimental burrow. Workers exhibited the highest
      frequency of workload compared to other castes. The presence of a queen activated
      the workload by other individuals. Individuals showed a consistent workload in a
      particular direction so as to bias the soil distribution. These results suggest
      that individuals have a consensus on soil distribution and that the queen plays a
      distinct role. In experiment 2, we placed the odour of a queen in one of four
      cells and observed its effect on other individuals' workload and soil
      distribution. Relative to other cells, individuals frequently dug in the queen
      cell so the amount of soil in the queen cell decreased. These results suggest
      that queen odour is an important cue in coordinated workload and soil
      distribution in this species.

PMID- 22957086
TI  - The effect of unilateral adrenalectomy on transformation of adrenal medullary
      chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.
AB  - BACKGROUND: Decreased epinephrine (EPI) is an important underlying factor of
      bronchoconstriction in asthma. Exogenous beta(2)-adrenergic receptor agonist is
      one of the preferred options to treat asthma. We previously showed that this
      phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a
      neuron phenotype. However, the underlying molecular mechanism is not fully
      understood. To further explore this, an asthmatic model with unilateral
      adrenalectomy was established in this study. METHODOLOGY/PRINCIPAL FINDINGS:
      Thirty-two rats were randomly into four groups (n = 8 each) control rats
      (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic
      rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s
      asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with
      ovalbumin (OVA). The pathological changes in adrenal medulla tissues were
      observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N
      methyl transferase (PNMT), were measured. Peripherin, a type III intermediate
      filament protein, was also detected in each group. The asthmatic rats presented
      with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s
      asthmatic rats presented more serious pathological changes than those in
      asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic
      rats were significantly decreased, as compared with levels in controls (P<0.05),
      and a further decline was observed in s-asthmatic rats (P<0.05). The expression
      of peripherin was higher in the asthmatic rats than in the controls, and the
      highest level was found in the s-asthmatic rats (P<0.05).
      CONCLUSION/SIGNIFICANCE: Compared with asthmatic rats and s-control rats, the
      transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic
      rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by
      reduced EPI and PNMT, and increased peripherin expression. This result provides
      further evidence to support the notion that phenotype alteration of AMCCs
      contributes to asthma pathogenesis.

PMID- 22957087
TI  - Dissociation of detection and discrimination of pure tones following bilateral
      lesions of auditory cortex.
AB  - It is well known that damage to the peripheral auditory system causes deficits in
      tone detection as well as pitch and loudness perception across a wide range of
      frequencies. However, the extent to which to which the auditory cortex plays a
      critical role in these basic aspects of spectral processing, especially with
      regard to speech, music, and environmental sound perception, remains unclear.
      Recent experiments indicate that primary auditory cortex is necessary for the
      normally-high perceptual acuity exhibited by humans in pure-tone frequency
      discrimination. The present study assessed whether the auditory cortex plays a
      similar role in the intensity domain and contrasted its contribution to sensory
      versus discriminative aspects of intensity processing. We measured intensity
      thresholds for pure-tone detection and pure-tone loudness discrimination in a
      population of healthy adults and a middle-aged man with complete or near-complete
      lesions of the auditory cortex bilaterally. Detection thresholds in his left and
      right ears were 16 and 7 dB HL, respectively, within clinically-defined normal
      limits. In contrast, the intensity threshold for monaural loudness discrimination
      at 1 kHz was 6.5 +/- 2.1 dB in the left ear and 6.5 +/- 1.9 dB in the right ear
      at 40 dB sensation level, well above the means of the control population (left
      ear: 1.6 +/- 0.22 dB; right ear: 1.7 +/- 0.19 dB). The results indicate that
      auditory cortex lowers just-noticeable differences for loudness discrimination by
      approximately 5 dB but is not necessary for tone detection in quiet. Previous
      human and Old-world monkey experiments employing lesion-effect, neurophysiology,
      and neuroimaging methods to investigate the role of auditory cortex in intensity
      processing are reviewed.

PMID- 22957088
TI  - Seroprevalence of chronic hepatitis B virus infection and prior immunity in
      immigrants and refugees: a systematic review and meta-analysis.
AB  - BACKGROUND: International migrants experience increased mortality from
      hepatocellular carcinoma compared to host populations, largely due to undetected
      chronic hepatitis B infection (HBV). We conducted a systematic review of the
      seroprevalence of chronic HBV and prior immunity in migrants arriving in low HBV
      prevalence countries to identify those at highest risk in order to guide disease
      prevention and control strategies. METHODS AND FINDINGS: Medline, Medline In
      Process, EMBASE and the Cochrane Database of Systematic Reviews were searched.
      Studies that reported HBV surface antigen or surface antibodies in migrants were
      included. The seroprevalence of chronic HBV and prior immunity were pooled by
      region of origin and immigrant class, using a random-effects model. A random
      effects logistic regression was performed to explore heterogeneity. The number of
      chronically infected migrants in each immigrant-receiving country was estimated
      using the pooled HBV seroprevalences and country-specific census data. A total of
      110 studies, representing 209,822 immigrants and refugees were included. The
      overall pooled seroprevalence of infection was 7.2% (95% CI: 6.3%-8.2%) and the
      seroprevalence of prior immunity was 39.7% (95% CI: 35.7%-43.9%). HBV
      seroprevalence differed significantly by region of origin. Migrants from East
      Asia and Sub-Saharan Africa were at highest risk and migrants from Eastern Europe
      were at an intermediate risk of infection. Region of origin, refugee status and
      decade of study were independently associated with infection in the adjusted
      random-effects logistic model. Almost 3.5 million migrants (95% CI: 2.8-4.5
      million) are estimated to be chronically infected with HBV. CONCLUSIONS: The
      seroprevalence of chronic HBV infection is high in migrants from most world
      regions, particularly among those from East Asia, Sub-Saharan Africa and Eastern
      Europe, and more than 50% were found to be susceptible to HBV. Targeted screening
      and vaccination of international migrants can become an important component of
      HBV disease control efforts in immigrant-receiving countries.

PMID- 22957089
TI  - A unique Kelch domain phosphatase in Plasmodium regulates ookinete morphology,
      motility and invasion.
AB  - Signalling through post-translational modification (PTM) of proteins is a process
      central to cell homeostasis, development and responses to external stimuli. The
      best characterised PTM is protein phosphorylation which is reversibly catalysed
      at specific residues through the action of protein kinases (addition) and
      phosphatases (removal). Here, we report characterisation of an orphan protein
      phosphatase that possesses a domain architecture previously only described in
      Plantae. Through gene disruption and the production of active site mutants, the
      enzymatically active Protein Phosphatase containing Kelch-Like domains (PPKL,
      PBANKA_132950) is shown to play an essential role in the development of an
      infectious ookinete. PPKL is produced in schizonts and female gametocytes, is
      maternally inherited where its absence leads to the development of a malformed,
      immotile, non-infectious ookinete with an extended apical protrusion. The
      distribution of PPKL includes focussed localization at the ookinete apical tip
      implying a link between its activity and the correct deployment of the apical
      complex and microtubule cytoskeleton. Unlike wild type parasites, ppkl(-)
      ookinetes do not have a pronounced apical distribution of their micronemes yet
      secretion of microneme cargo is unaffected in the mutant implying that release of
      microneme cargo is either highly efficient at the malformed apical prominence or
      secretion may also occur from other points of the parasite, possibly the
      pellicular pores.

PMID- 22957090
TI  - Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by
      down-regulating the expression of VEGF and MMP-7 in gastric cancer.
AB  - BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a
      glycoprotein that functions to inhibit angiogenesis, proliferation, and invasion
      in different types of cancer. The ability of SPARC to modulate neovascularisation
      is believed to be mediated in part by its ability to modulate the expression of
      vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).
      In this study, we aimed to determine the effect of SPARC expression in gastric
      cancer cells on proliferation and angiogenesis in vitro and in vivo. METHOD: We
      evaluated expression of SPARC in seven human gastric cancer cell lines. Then we
      established a stably transfected SPARC overexpressed cell line (BGC-SP) and a
      stably transfected SPARC knock-down cell line (HGC-sh). The effect of SPARC
      overexpression and SPARC silencing was studied by examining capillary formation
      of HUVECs in vitro and a dorsal skin-fold chamber model in vivo. Quantitative
      real-time PCR and western blotting were performed to detect if the expressions of
      VEGF and MMP-7 were modulated by SPARC expression. To further determine the
      effect of SPARC expression on angiogenesis in vivo, xenograft models were
      established and microvessel density (MVD) of different clones were detected by
      immunohistochemistry. RESULTS: Endogenous SPARC overexpression inhibited the
      expression of VEGF and MMP-7, as well as the angiogenesis induced by BGC-SP
      cells. Correspondingly, SPARC silencing increased the expression of VEGF and MMP
      7, as well as the angiogenesis induced by HGC-sh cells. Elevated angiogenesis
      induced by SPARC silencing in HGC-sh cells was decreased when VEGF was
      neutralised by antibodies, and MMP-7 was knocked down in vitro. CONCLUSION: SPARC
      suppresses angiogenesis of gastric cancer by down-regulating the expression of
      VEGF and MMP-7.

PMID- 22957091
TI  - An analytical approach for estimating fossil record and diversification events in
      sharks, skates and rays.
AB  - BACKGROUND: Modern selachians and their supposed sister group (hybodont sharks)
      have a long and successful evolutionary history. Yet, although selachian remains
      are considered relatively common in the fossil record in comparison with other
      marine vertebrates, little is known about the quality of their fossil record.
      Similarly, only a few works based on specific time intervals have attempted to
      identify major events that marked the evolutionary history of this group.
      METHODOLOGY/PRINCIPAL FINDINGS: Phylogenetic hypotheses concerning modern
      selachians' interrelationships are numerous but differ significantly and no
      consensus has been found. The aim of the present study is to take advantage of
      the range of recent phylogenetic hypotheses in order to assess the fit of the
      selachian fossil record to phylogenies, according to two different branching
      methods. Compilation of these data allowed the inference of an estimated range of
      diversity through time and evolutionary events that marked this group over the
      past 300 Ma are identified. Results indicate that with the exception of high
      taxonomic ranks (orders), the selachian fossil record is by far imperfect,
      particularly for generic and post-Triassic data. Timing and amplitude of the
      various identified events that marked the selachian evolutionary history are
      discussed. CONCLUSION/SIGNIFICANCE: Some identified diversity events were
      mentioned in previous works using alternative methods (Early Jurassic, mid
      Cretaceous, K/T boundary and late Paleogene diversity drops), thus reinforcing
      the efficiency of the methodology presented here in inferring evolutionary
      events. Other events (Permian/Triassic, Early and Late Cretaceous
      diversifications; Triassic/Jurassic extinction) are newly identified.
      Relationships between these events and paleoenvironmental characteristics and
      other groups' evolutionary history are proposed.

PMID- 22957092
TI  - RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell
      proliferation, angiogenesis, and inducing apoptosis.
AB  - Deletion of the short arm of chromosome 3 is one of the most frequent genetic
      alterations in many solid tumors including nasopharyngeal carcinoma (NPC),
      suggesting the existence of one or more tumor suppressor genes (TSGs) within the
      frequently deleted region. A putative TSG RBMS3 (RNA binding motif, single
      stranded interacting protein 3), located at 3p24-p23, has been identified in our
      previous study. Here, we reported that downregulation of RBMS3 was detected in
      3/3 NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional studies
      using both overexpression and suppression systems demonstrated that RBMS3 has a
      strong tumor suppressive role in NPC. The tumor suppressive mechanism of RBMS3
      was associated with its role in cell cycle arrest at the G1/S checkpoint by
      upregulating p53 and p21, downregulating cyclin E and CDK2, and the subsequent
      inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro
      apoptotic role in a mitochondrial-dependent manner via activation of caspase-9
      and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated
      by down-regulation of MMP2 and beta-catenin and inactivation of its downstream
      targets, including cyclin-D1, c-Myc, MMP7, and MMP9. Taken together, our findings
      define a function for RBMS3 as an important tumor suppressor gene in NPC.

PMID- 22957093
TI  - Improving lambda red genome engineering in Escherichia coli via rational removal
      of endogenous nucleases.
AB  - Lambda Red recombineering is a powerful technique for making targeted genetic
      changes in bacteria. However, many applications are limited by the frequency of
      recombination. Previous studies have suggested that endogenous nucleases may
      hinder recombination by degrading the exogenous DNA used for recombineering. In
      this work, we identify ExoVII as a nuclease which degrades the ends of single
      stranded DNA (ssDNA) oligonucleotides and double-stranded DNA (dsDNA) cassettes.
      Removing this nuclease improves both recombination frequency and the inheritance
      of mutations at the 3' ends of ssDNA and dsDNA. Extending this approach, we show
      that removing a set of five exonucleases (RecJ, ExoI, ExoVII, ExoX, and Lambda
      Exo) substantially improves the performance of co-selection multiplex automatable
      genome engineering (CoS-MAGE). In a given round of CoS-MAGE with ten ssDNA
      oligonucleotides, the five nuclease knockout strain has on average 46% more
      alleles converted per clone, 200% more clones with five or more allele
      conversions, and 35% fewer clones without any allele conversions. Finally, we use
      these nuclease knockout strains to investigate and clarify the effects of
      oligonucleotide phosphorothioation on recombination frequency. The results
      described in this work provide further mechanistic insight into recombineering,
      and substantially improve recombineering performance.

PMID- 22957094
TI  - Rod photoreceptor ribbon synapses in DBA/2J mice show progressive age-related
      structural changes.
AB  - The DBA/2J mouse is a commonly used animal model in glaucoma research. The eyes
      of DBA/2J mice show severe age-related changes that finally lead to the
      degeneration of retinal ganglion cells and the optic nerve. Recent
      electroretinogram studies identified functional deficits, which suggest that also
      photoreceptor cells are involved in the pathological processes occurring in the
      DBA/2J mouse retina. In a comparative study, we examined anatomical and molecular
      changes in the retinae of DBA/2J and C57BL/6 control mice with light and electron
      microscopy and with PCR analyses. In the retina of the DBA/2J mouse, we found a
      thinning of the outer plexiform layer, the first synaptic layer in the transfer
      of visual signals, and age-dependent and progressive degenerative structural
      changes at rod photoreceptor ribbon synapses. The structural ribbon changes
      represent a photoreceptor synaptic phenotype that has not yet been described in
      this animal model of secondary angle-closure glaucoma. Furthermore, genes of the
      classical complement cascade were upregulated in the photoreceptor cells of aging
      DBA/2J mice, suggesting a putative link between ribbon synapse degradation and
      the innate immune system.

PMID- 22957095
TI  - Benefits of extra begging fail to compensate for immunological costs in southern
      shrike (Lanius meridionalis) nestlings.
AB  - Theoretical models aimed at explaining the evolution of honest, informative
      begging signals employed by nestling birds to solicit food from their parents,
      require that dishonest signalers incur a net viability cost in order to prevent
      runaway escalation of signal intensity over evolutionary time. Previous attempts
      to determine such a cost empirically have identified two candidate physiological
      costs associated with exaggerated begging: a growth and an immunological cost.
      However, they failed to take into account the fact that those costs are
      potentially offset by the fact that nestlings that invest more in begging are
      also likely to obtain more food. In this study, we test experimentally whether a
      25% increase in ingested food compensates for growth and immunological costs of
      extra begging in southern shrike (Lanius meridionalis) nestlings. Three nestmates
      matched by size were given three treatments: low begging, high begging-same food
      intake, and high begging-extra food intake. We found that, while a higher food
      intake did effectively compensate for the growth cost, it failed to compensate
      for the immunological cost, measured as T-cell mediated immune response against
      an innocuous mitogen. Thus, we show for the first time that escalated begging has
      an associated physiological net cost likely to affect nestling survival
      negatively.

PMID- 22957096
TI  - Graft versus host disease in the bone marrow, liver and thymus humanized mouse
      model.
AB  - Mice bearing a "humanized" immune system are valuable tools to experimentally
      manipulate human cells in vivo and facilitate disease models not normally
      possible in laboratory animals. Here we describe a form of GVHD that develops in
      NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS
      BLT mice). The skin, lungs, gastrointestinal tract and parotid glands are
      affected with progressive inflammation and sclerosis. Although all mice showed
      involvement of at least one organ site, the incidence of overt clinical disease
      was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking
      the IL2 common gamma chain (NOD/SCID/gammac(-/-)) delayed the onset of disease,
      but ultimately did not affect incidence. Genetic analysis revealed that
      particular donor HLA class I alleles influenced the risk for the development of
      GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+
      T cells into the skin and a shift towards Th1 cytokine production. GVHD also
      induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class
      II+ macrophage population. The presence of xenogenic GVHD in BLT mice both
      presents a major obstacle in the use of humanized mice and an opportunity to
      conduct preclinical studies on GVHD in a humanized model.

PMID- 22957097
TI  - Antibody protection reveals extended epitopes on the human TSH receptor.
AB  - Stimulating, and some blocking, antibodies to the TSH receptor (TSHR) have
      conformation-dependent epitopes reported to involve primarily the leucine rich
      repeat region of the ectodomain (LRD). However, successful crystallization of
      TSHR residues 22-260 has omitted important extracellular non-LRD residues
      including the hinge region which connects the TSHR ectodomain to the
      transmembrane domain and which is involved in ligand induced signal transduction.
      The aim of the present study, therefore, was to determine if TSHR antibodies
      (TSHR-Abs) have non-LRD binding sites outside the LRD. To obtain this information
      we employed the method of epitope protection in which we first protected TSHR
      residues 1-412 with intact TSHR antibodies and then enzymatically digested the
      unprotected residues. Those peptides remaining were subsequently delineated by
      mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR
      Ab crystal contact residues were protected by this technique which may reflect
      the higher binding energies of certain residues detected in this approach.
      Comparing the protected epitopes of two stimulating TSHR-Abs we found both
      similarities and differences but both antibodies also contacted the hinge region
      and the amino terminus of the TSHR following the signal peptide and encompassing
      cysteine box 1 which has previously been shown to be important for TSH binding
      and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of
      binding regions but the residues that it contacted on the LRD were again
      distinct. These data demonstrated that conformationally dependent TSHR-Abs had
      epitopes not confined to the LRDs but also incorporated epitopes not revealed in
      the available crystal structure. Furthermore, the data also indicated that in
      addition to overlapping contact regions within the LRD, there are unique epitope
      patterns for each of the antibodies which may contribute to their functional
      heterogeneity.

PMID- 22957098
TI  - Sex differences in the development of malignancies among end-stage renal disease
      patients: a nationwide population-based follow-up study in Taiwan.
AB  - Increasing evidence indicates that end-stage renal disease (ESRD) is associated
      with the morbidity of cancer. However, whether different dialysis modality and
      sex effect modify the cancer risks in ESRD patients remains unclear. A total of
      3,570 newly diagnosed ESRD patients and 14,280 controls matched for age, sex,
      index month, and index year were recruited from the National Health Insurance
      Research Database in Taiwan. The ESRD status was ascertained from the registry of
      catastrophic illness patients. The incidence of cancer was identified through
      cross-referencing with the National Cancer Registry System. The Cox proportional
      hazards model and the Kaplan-Meier method were used for analyses. A similar
      twofold increase in cancer risk was observed among ESRD patients undergoing
      hemodialysis (HD) or peritoneal dialysis (PD) after adjusting for other potential
      risk factors. Patients with the highest cancer risk, approximately fourfold
      increased risk, were those received renal transplants. Urothelial carcinoma (UC)
      had the highest incidence in HD and PD patients. However, renal cell carcinoma
      (RCC) had the highest incidence in the renal transplantation (RT) group. In
      addition, female patients undergoing RT or PD had a higher incidence of RCC and
      UC, respectively. Male patients under HD had both higher incidence of RCC and UC.
      In conclusion, different dialysis modality could modify the cancer risks in ESRD
      patients. We also found sex effect on genitourinary malignancy when they are
      under different dialysis modality.

PMID- 22957099
TI  - Towards measuring brain function on groups of people in the real world.
AB  - In three studies, EEGs from three groups of participants were recorded during
      progressively more real world situations after drinking alcoholic beverages that
      brought breath alcohol contents near the limit for driving in California 30
      minutes after drinking. A simple equation that measured neurophysiological
      effects of alcohol in the first group of 15 participants performing repetitive
      cognitive tasks was applied to a second group of 15 operating an automobile
      driving simulator, and to a third group of 10 ambulatory people recorded
      simultaneously during a cocktail party. The equation derived from the first group
      quantified alcohol's effect by combining measures of higher frequency (beta) and
      lower frequency (theta) power into a single score. It produced an Area Under the
      Receiver Operator Characteristic Curve of .73 (p<.05; 67% sensitivity in
      recognizing alcohol and 87% specificity in recognizing placebo). Applying the
      same equation to the second group operating the driving simulator, AUC was .95,
      (p<.0001; 93% sensitivity and 73% specificity), while for the cocktail party
      group AUC was .87 (p<.01; 80% sensitivity and 80% specificity). EEG scores were
      significantly related to breath alcohol content in all studies. Some individuals
      differed markedly from the overall response evident in their respective groups.
      The feasibility of measuring the neurophysiological effect of a psychoactive
      substance from an entire group of ambulatory people at a cocktail party suggests
      that future studies may be able to fruitfully apply brain function measures
      derived under rigorously controlled laboratory conditions to assess drug effects
      on groups of people interacting in real world situations.

PMID- 22957101
TI  - Self-reported use of personal protective equipment among Chinese critical care
      clinicians during 2009 H1N1 influenza pandemic.
AB  - BACKGROUND: Critically ill patients with 2009 H1N1 influenza are often treated in
      intensive care units (ICUs), representing significant risk of nosocomial
      transmission to critical care clinicians and other patients. Despite a large body
      of literature and guidelines recommending infection control practices, numerous
      barriers have been identified in ICUs, leading to poor compliance to the use of
      personal protective equipment (PPE). The use of PPE among critical care
      clinicians has not been extensively evaluated, especially during the pandemic
      influenza. This study examined the knowledge, attitudes, and self-reported
      behaviors, and barriers to compliance with the use of PPE among ICU healthcare
      workers (HCWs) during the pandemic influenza. METHODOLOGY/PRINCIPAL FINDINGS: A
      survey instrument consisting of 36 questions was developed and mailed to all HCWs
      in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other
      professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty
      six percent of respondents reported having received training program of pandemic
      influenza before they cared for H1N1 patients, while 77% reported to have
      adequate knowledge of self and patient protection. Only 18% of respondents were
      able to correctly identify all components of PPE, and 55% reported high
      compliance (>80%) with PPE use during patient care. In multivariate analysis,
      vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use,
      organizational factors such as availability of PPE in ICU, and patient
      information of influenza precautions, as well as reprimand for noncompliance by
      the supervisors were associated with high compliance, whereas negative attitudes
      towards PPE use and violation of PPE use were independent predictors of low
      compliance. CONCLUSION/SIGNIFICANCE: Knowledge and self-reported compliance to
      recommended PPE use among Chinese critical care clinicians is suboptimal. The
      perceived barriers should be addressed in order to close the significant gap
      between perception and knowledge or behavior.

PMID- 22957100
TI  - Agnathan VIP, PACAP and their receptors: ancestral origins of today's highly
      diversified forms.
AB  - VIP and PACAP are pleiotropic peptides belonging to the secretin superfamily of
      brain-gut peptides and interact specifically with three receptors (VPAC(1),
      PAC(1) and VPAC(2)) from the class II B G protein-coupled receptor family. There
      is immense interest regarding their molecular evolution which is often described
      closely alongside gene and/or genome duplications. Despite the wide array of
      information available in various vertebrates and one invertebrate the tunicate,
      their evolutionary origins remain unresolved. Through searches of genome
      databases and molecular cloning techniques, the first lamprey VIP/PACAP ligands
      and VPAC receptors are identified from the Japanese lamprey. In addition, two
      VPAC receptors (VPACa/b) are identified from inshore hagfish and ligands
      predicted for sea lamprey. Phylogenetic analyses group these molecules into their
      respective PHI/VIP, PRP/PACAP and VPAC receptor families and show they resemble
      ancestral forms. Japanese lamprey VIP/PACAP peptides synthesized were tested with
      the hagfish VPAC receptors. hfVPACa transduces signal via both adenylyl cylase
      and phospholipase C pathways, whilst hfVPACb was only able to transduce through
      the calcium pathway. In contrast to the widespread distribution of VIP/PACAP
      ligands and receptors in many species, the agnathan PACAP and VPAC receptors were
      found almost exclusively in the brain. In situ hybridisation further showed their
      abundance throughout the brain. The range of VIP/PACAP ligands and receptors
      found are highly useful, providing a glimpse into the evolutionary events both at
      the structural and functional levels. Though representative of ancestral forms,
      the VIP/PACAP ligands in particular have retained high sequence conservation
      indicating the importance of their functions even early in vertebrate evolution.
      During these nascent stages, only two VPAC receptors are likely responsible for
      eliciting functions before evolving later into specific subtypes post-Agnatha. We
      also propose VIP and PACAP's first functions to predominate in the brain,
      evolving alongside the central nervous system, subsequently establishing
      peripheral functions.

PMID- 22957102
TI  - Abnormally low and high ankle-brachial indices are independently associated with
      increased left ventricular mass index in chronic kidney disease.
AB  - Abnormally low and high ankle-brachial indices (ABIs) are associated with high
      cardiovascular morbidity and mortality in patients with chronic kidney disease
      (CKD), but the mechanisms responsible for the association are not fully known.
      This study is designed to assess whether there is a significant correlation
      between abnormal ABI and echocariographic parameters in patients with CKD stages
      3-5. A total of 684 pre-dialysis CKD patients were included in the study. The ABI
      was measured using an ABI-form device. Patients were classified into ABI <0.9, >=
      0.9 to <1.3, and >= 1.3. Clinical and echocariographic parameters were compared
      and analyzed. Compared with patients with ABI of >= 0.9 to <1.3, the values of
      left ventricular mass index (LVMI) were higher in patients with ABI <0.9 and ABI
      >= 1.3 (P <= 0.004). After the multivariate analysis, patients with ABI <0.9
      (beta = 0.099, P = 0.004) and ABI >= 1.3 (beta = 0.143, P<0.001) were
      independently associated with increased LVMI. Besides, increased LVMI (odds
      ratio, 1.017; 95% confidence interval, 1.002 to 1.033; P = 0.031) was also
      significantly associated with ABI <0.9 or ABI >=1.3. Our study in patients of CKD
      stages 3-5 demonstrated abnormally low and high ABIs were positively associated
      with LVMI. Future studies are required to determine whether increased LVMI is a
      causal intermediary between abnormal ABI and adverse cardiovascular outcomes in
      CKD.

PMID- 22957103
TI  - A small molecule inhibitor partitions two distinct pathways for trafficking of
      tonoplast intrinsic proteins in Arabidopsis.
AB  - Tonoplast intrinsic proteins (TIPs) facilitate the membrane transport of water
      and other small molecules across the plant vacuolar membrane, and members of this
      family are expressed in specific developmental stages and tissue types. Delivery
      of TIP proteins to the tonoplast is thought to occur by vesicle-mediated traffic
      from the endoplasmic reticulum to the vacuole, and at least two pathways have
      been proposed, one that is Golgi-dependent and another that is Golgi-independent.
      However, the mechanisms for trafficking of vacuolar membrane proteins to the
      tonoplast remain poorly understood. Here we describe a chemical genetic approach
      to unravel the mechanisms of TIP protein targeting to the vacuole in Arabidopsis
      seedlings. We show that members of the TIP family are targeted to the vacuole via
      at least two distinct pathways, and we characterize the bioactivity of a novel
      inhibitor that can differentiate between them. We demonstrate that, unlike for
      TIP1;1, trafficking of markers for TIP3;1 and TIP2;1 is insensitive to Brefeldin
      A in Arabidopsis hypocotyls. Using a chemical inhibitor that may target this BFA
      insensitive pathway for membrane proteins, we show that inhibition of this
      pathway results in impaired root hair growth and enhanced vacuolar targeting of
      the auxin efflux carrier PIN2 in the dark. Our results indicate that the vacuolar
      targeting of PIN2 and the BFA-insensitive pathway for tonoplast proteins may be
      mediated in part by common mechanisms.

PMID- 22957104
TI  - Topography of Gng2- and NetrinG2-expression suggests an insular origin of the
      human claustrum.
AB  - The claustrum has been described in the forebrain of all mammals studied so far.
      It has been suggested that the claustrum plays a role in the integration of
      multisensory information: however, its detailed structure and function remain
      enigmatic. The human claustrum is a thin, irregular, sheet of grey matter located
      between the inner surface of the insular cortex and the outer surface of the
      putamen. Recently, the G-protein gamma2 subunit (Gng2) was proposed as a specific
      claustrum marker in the rat, and used to better delineate its anatomical
      boundaries and connections. Additional claustral markers proposed in mammals
      include Netrin-G2 in the monkey and latexin in the cat. Here we report the
      expression and distribution of Gng2 and Netrin-G2 in human post-mortem samples of
      the claustrum and adjacent structures. Gng2 immunoreactivity was detected in the
      neuropil of the claustrum and of the insular cortex but not in the putamen. A
      faint labelling was present also in the external and extreme capsules. Double
      labelling experiments indicate that Gng2 is also expressed in glial cells. Netrin
      G2 labelling was seen in neuronal cell bodies throughout the claustrum and the
      insular cortex but not in the medially adjacent putamen. No latexin
      immunoreactive element was detected in the claustrum or adjacent structures. Our
      results confirm that both the Gng2 and the Netrin-G2 proteins show an affinity to
      the claustrum and related formations also in the human brain. The presence of
      Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the
      putamen, suggests a possible common ontogeny of the claustrum and insula.

PMID- 22957105
TI  - Expression of aromatase in radial glial cells in the brain of the Japanese eel
      provides insight into the evolution of the cyp191a gene in Actinopterygians.
AB  - The cyp19a1 gene that encodes aromatase, the only enzyme permitting conversion of
      C19 aromatizable androgens into estrogens, is present as a single copy in the
      genome of most vertebrate species, except in teleosts in which it has been
      duplicated. This study aimed at investigating the brain expression of a cyp19a1
      gene expressed in both gonad and brain of Japanese eel, a basal teleost. By means
      of immunohistochemistry and in situ hybridization, we show that cyp19a1 is
      expressed only in radial glial cells of the brain and in pituitary cells.
      Treatments with salmon pituitary homogenates (female) or human chorionic
      gonadotrophin (male), known to turn on steroid production in immature eels,
      strongly stimulated cyp19a1 messenger and protein expression in radial glial
      cells and pituitary cells. Using double staining studies, we also showed that
      aromatase-expressing radial glial cells exhibit proliferative activity in both
      the brain and the pituitary. Altogether, these data indicate that brain and
      pituitary expression of Japanese eel cyp19a1 exhibits characteristics similar to
      those reported for the brain specific cyp19a1b gene in teleosts having duplicated
      cyp19a1 genes. This supports the hypothesis that, despite the fact that eels also
      underwent the teleost specific genome duplication, they have a single cyp19a1
      expressed in both brain and gonad. Such data also suggest that the intriguing
      features of brain aromatase expression in teleost fishes were not gained after
      the whole genome duplication and may reflect properties of the cyp19a1 gene of
      ancestral Actinopterygians.

PMID- 22957107
TI  - Optimal isolation of functional Foxp3+ induced regulatory T cells using DEREG
      mice.
AB  - Foxp3 reporter mice including DEREG (DEpletion of REGulatory T cells) mice have
      greatly helped in exploring the biology of Foxp3(+) Tregs. DEREG mice express a
      DTR-eGFP fusion protein under the control of a bacterial artificial chromosome
      (BAC)-encoded Foxp3 promoter, allowing the viable isolation and inducible
      depletion of Foxp3(+) Tregs. Adaptive Tregs differentiated in vitro to express
      Foxp3 (iTregs) are gaining high interest as potential therapeutics for
      inflammatory conditions such as autoimmunity, allergy and transplant rejection.
      However, selective isolation of Foxp3(+) iTregs with a stable phenotype still
      remains to be a problem, especially in the human setting. While screening for
      culture conditions to generate stable CD4(+)Foxp3(+) iTregs from DEREG mice, with
      maximum suppressive activity, we observed an unexpected dichotomy of eGFP and
      Foxp3 expression which is not seen in ex vivo isolated cells from DEREG mice.
      Further characterization of eGFP(+)Foxp3(-) cells revealed relatively lower CD25
      expression and a lack of suppressive activity in vitro. Similarly, eGFP(-) cells
      isolated from the same cultures were not suppressive despite of a broad CD25
      expression reflecting mere T cell activation. In contrast, eGFP(+)Foxp3(+) iTregs
      exhibited potent suppressive activity comparable to that of natural
      eGFP(+)Foxp3(+) Tregs, emphasizing the importance of isolating Foxp3 expressing
      iTregs. Interestingly, the use of plate-bound anti-CD3 and anti-CD28 or Flt3L
      driven BMDC resulted in considerable resolution of the observed dichotomy. In
      summary, we defined culture conditions for efficient generation of
      eGFP(+)Foxp3(+) iTregs by use of DEREG mice. Isolation of functional Foxp3(+)
      iTregs using DEREG mice can also be achieved under sub-optimal conditions based
      on the magnitude of surface CD25 expression, in synergy with transgene encoded
      eGFP. Besides, the reported phenomenon may be of general interest for exploring
      Foxp3 gene regulation, given that Foxp3 and eGFP expression are driven from
      distinct Foxp3 loci and because this dichotomy preferentially occurs only under
      defined in vitro conditions.

PMID- 22957106
TI  - Reciprocal regulation of axonal Filopodia and outgrowth during neuromuscular
      junction development.
AB  - BACKGROUND: The assembly of the vertebrate neuromuscular junction (NMJ) is
      initiated when nerve and muscle first contact each other by filopodial processes
      which are thought to enable close interactions between the synaptic partners and
      facilitate synaptogenesis. We recently reported that embryonic Xenopus spinal
      neurons preferentially extended filopodia towards cocultured muscle cells and
      that basic fibroblast growth factor (bFGF) produced by muscle activated neuronal
      FGF receptor 1 (FGFR1) to induce filopodia and favor synaptogenesis.
      Intriguingly, in an earlier study we found that neurotrophins (NTs), a different
      set of target-derived factors that act through Trk receptor tyrosine kinases,
      promoted neuronal growth but hindered presynaptic differentiation and NMJ
      formation. Thus, here we investigated how bFGF- and NT-signals in neurons jointly
      elicit presynaptic changes during the earliest stages of NMJ development.
      METHODOLOGY/PRINCIPAL FINDINGS: Whereas forced expression of wild-type TrkB in
      neurons reduced filopodial extension and triggered axonal outgrowth, expression
      of a mutant TrkB lacking the intracellular kinase domain enhanced filopodial
      growth and slowed axonal advance. Neurons overexpressing wild-type FGFR1 also
      displayed more filopodia than control neurons, in accord with our previous
      findings, and, notably, this elevation in filopodial density was suppressed when
      neurons were chronically treated from the beginning of the culture period with
      BDNF, the NT that specifically activates TrkB. Conversely, inhibition by BDNF of
      NMJ formation in nerve-muscle cocultures was partly reversed by the
      overexpression of bFGF in muscle. CONCLUSIONS: Our results suggest that the
      balance between neuronal FGFR1- and TrkB-dependent filopodial assembly and axonal
      outgrowth regulates the establishment of incipient NMJs.

PMID- 22957108
TI  - Assessing Developmental Trajectories of Sexual Minority Youth: Discrepant
      Findings from a Life History Calendar and a Self-Administered Survey.
AB  - Research suggests that the timing and sequence of sexual identity development
      milestones impacts myriad health and mental health outcomes for sexual minority
      youth. Because these milestone events are typically assessed retrospectively,
      traditional data collection approaches are limited by recall bias and lack of
      precision in the recording of milestone events, which may conceal the
      distinctions between events and distort the recording of youths' developmental
      trajectories. The purpose of this exploratory study was to compare responses to
      questions about psychosexual milestones elicited by a Life History Calendar and a
      self-administered survey. Results indicated discrepancies in the reported
      occurrence and timing of milestone events between the survey and Life History
      Calendar. Differences in the timing of specific milestone events ranged from two
      months to 15 years. Implications of these discordant findings for sexual minority
      youth are discussed.

PMID- 22957109
TI  - Acceptance of Evolution Increases with Student Academic Level: A Comparison
      Between a Secular and a Religious College.
AB  - Acceptance of evolution among the general public, high schools, teachers, and
      scientists has been documented in the USA; little is known about college
      students' views on evolution; this population is relevant since it transits from
      a high-school/parent-protective environment to an independent role in societal
      decisions. Here we compare perspectives about evolution, creationism, and
      intelligent design (ID) between a secular (S) and a religious (R) college in the
      Northeastern USA. Interinstitutional comparisons showed that 64% (mean S + R)
      biology majors vs. 42/62% (S/R) nonmajors supported the exclusive teaching of
      evolution in science classes; 24/29% (S/R) biology majors vs. 26/38% (S/R)
      nonmajors perceived ID as both alternative to evolution and/or scientific theory
      about the origin of life; 76% (mean S + R) biology majors and nonmajors accepted
      evolutionary explanations about the origin of life; 86% (mean S + R) biology
      majors vs. 79% (mean S + R) nonmajors preferred science courses where human
      evolution is discussed; 76% (mean S+R) biology majors vs. 79% (mean S + R)
      nonmajors welcomed questions about evolution in exams and/or thought that such
      questions should always be in exams; and 66% (mean S + R) biology majors vs. 46%
      (mean S + R) nonmajors admitted they accept evolution openly and/or privately.
      Intrainstitutional comparisons showed that overall acceptance of evolution among
      biologists (S or R) increased gradually from the freshman to the senior year, due
      to exposure to upper-division courses with evolutionary content. College
      curricular/pedagogical reform should fortify evolution literacy at all education
      levels, particularly among nonbiologists.

PMID- 22957110
TI  - Tick-borne encephalitis is associated with low levels of interleukin-10 in
      cerebrospinal fluid.
AB  - Tick-borne encephalitis (TBE) is associated with higher morbidity and induces a
      stronger intrathecal immune activation than most other viral induced meningo
      encephalitis. The aim of this study was to investigate cytokine concentrations in
      cerebrospinal fluid (CSF) and serum in relation to aetiology and clinical course.
      Cytokines were analysed by Enzyme-linked Immuno Assay (ELISA) from 44 patients
      with TBE and from 36 patients with aseptic meningo-encephalitis of other
      aetiology (non-TBE). Significantly increased CSF levels of Interferon-gamma (IFN
      gamma), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1 receptor
      antagonist (IL-1ra), and soluble CD8 receptor (sCD8) were detected in both
      cohorts. Tumour necrosis factor-alpha (TNF-alpha showed low levels or was not
      detected in CSF in any group in the acute stage. However, the CSF levels of IL-10
      were significantly lower in TBE than in non-TBE cases 0-6 days after onset of
      encephalitis. The TBE patients with encephalitis had significantly lower IL-10
      CSF levels later in the clinical course (day 7-18) than TBE patients with
      meningeal disease. Increased IFN-gamma production, but low IL-10 secretion, may
      be of pathophysiological significance in TBE.

PMID- 22957111
TI  - Global ecology and epidemiology of Borrelia garinii spirochetes.
AB  - Lyme borreliosis (LB) is a tick-transmitted infectious disease caused by Borrelia
      burgdorferi sensu lato (s. l.). In Europe, three different Borrelia species are
      the main causative agents of LB: B. burgdorferi sensu stricto (s.s.), Borrelia
      afzelii, and Borrelia garinii. The latter depends heavily on birds as its main
      reservoir hosts. In fact, birds can act both as biological carriers of Borrelia
      and transporters of infected ticks. The seasonal migration of many bird species
      not only aid in the spread of B. garinii to new foci but also influence the high
      level of diversity found within this species. B. garinii have been isolated not
      only from terrestrial birds in Europe, but also from seabirds worldwide, and
      homology between isolates in these two different infection cycles suggests an
      overlap and exchange of strains. In addition, it has been shown that birds can
      maintain and spread B. garinii genotypes associated with LB in humans. This
      review article discusses the importance of birds in the ecology and epidemiology
      of B. garinii spirochetes.

PMID- 22957112
TI  - Dengue fever in returned Swedish travelers from Thailand.
AB  - The dengue viruses (DENV) are endemic in the tropical and sub-tropical countries
      and cause the most common arthropod-borne viral disease in humans. Travelers
      visiting endemic areas may both acquire and spread DENV infections, and this is
      the reason why prevention of mosquito bites is of crucial importance. Dengue
      fever (DF) has become the most common cause for tropical fever in Swedish
      tourists. Swedish data from 1995 to 2010 show that the number of DF cases has
      increased since the beginning of 2000; partly due to improved diagnostics based
      on IgM detection, and partly due to an increase in the number of tourists
      traveling to, and between, endemic areas. Young adults aged 20-29 are mostly
      affected, and epidemiological data indicate increased incidence rates from 2008
      onwards. Our data pose a call for attention when traveling to DENV endemic areas
      as well as an increased awareness among physicians when treating returning
      travelers.

PMID- 22957113
TI  - Influenza A viruses: an ecology review.
AB  - In humans, influenza A viruses cause yearly outbreaks with high morbidity and
      excess fatality rates as a direct effect. Placed in its ecological niche, however
      - in dabbling ducks - avian influenza virus (AIV) induces quite a mild disease.
      It is when the virus crosses the species barrier that pathogenic traits are
      attributed to infection. When infecting phylogenetically more distant species
      (i.e. chicken and turkeys), the AIV can cause high morbidity and may in some
      cases change the virus into a highly pathogenic variant with nearly 100% fatality
      rate. Being a very adaptable virus, these spill-over events are frequent and
      numerous species are susceptible to influenza virus. When a subtype of AIV that
      has not previously infected humans crosses the species barrier, adapts to humans,
      and spreads easily, a pandemic event is imminent. There is no cure for influenza
      infection and vaccination is a cumbersome endeavor so, currently, the strategy
      when a pandemic strikes is damage control. The interest in AIV ecology has
      increased dramatically since the beginning of the millennium as a key factor for
      preventive work for future pandemics. This review gives a broad overview of
      influenza A virus ecology: in the natural host, accidental hosts, new endemic
      hosts, and humans.

PMID- 22957114
TI  - The impact of multiple infections on wild animal hosts: a review.
AB  - Field parasitological studies consistently demonstrate the reality of
      polyparasitism in natural systems. However, only recently, studies from
      ecological and evolutionary fields have emphasised a broad spectrum of potential
      multiple infections-related impacts. The main goal of our review is to reunify
      the different approaches on the impacts of polyparasitism, not only from
      laboratory or human medical studies but also from field or theoretical studies.
      We put forward that ecological and epidemiological determinants to explain the
      level of polyparasitism, which regularly affects not only host body condition,
      survival or reproduction but also host metabolism, genetics or immune investment.
      Despite inherent limitations of all these studies, multiple infections should be
      considered more systematically in wildlife to better appreciate the importance of
      parasite diversity in wildlife, cumulative effects of parasitism on the ecology
      and evolution of their hosts.

PMID- 22957115
TI  - Clonal transmission, dual peak, and off-season cholera in Bangladesh.
AB  - Vibrio cholerae is an estuarine bacterium associated with a single peak of
      cholera (March-May) in coastal villages of Bangladesh. For an unknown reason,
      however, cholera occurs in a unique dual peak (March-May and September-November)
      pattern in the city of Dhaka that is bordered by a heavily polluted freshwater
      river system and flood embankment. In August 2007, extreme flooding was
      accompanied by an unusually severe diarrhea outbreak in Dhaka that resulted in a
      record high illness. This study was aimed to understand the unusual outbreak and
      if it was related to the circulation of a new V. cholerae clone. Nineteen V.
      cholerae isolated during the peak of the 2007 outbreak were subjected to
      extensive phenotypic and molecular analyses, including multi-locus genetic
      screening by polymerase chain reaction (PCR), sequence-typing of the ctxB gene,
      and pulsed-field gel electrophoresis (PFGE). Factors associated with the unusual
      incidence of cholera were determined and analysis of the disease severity was
      done. Overall, microbiological and molecular data confirmed that the
      hypervirulent V. cholerae was O1 biotype El Tor (ET) that possessed cholera toxin
      (CT) of the classical biotype. The PFGE (NotI) and dendrogram clustering
      confirmed that the strains were clonal and related to the pre-2007 variant ET
      from Dhaka and Matlab and resembled one of two distinct clones of the variant ET
      confirmed to be present in the estuarine ecosystem of Bangladesh. Results of the
      analyses of both diarrheal case data for three consecutive years (2006-2008) and
      regional hydroclimatology over three decades (1980-2009) clearly indicate that
      the pattern of cholera occurring in Dhaka, and not seen at other endemic sites,
      was associated with flood waters transmitting the infectious clone circulating
      via the fecal-oral route during and between the dual seasonal cholera peaks in
      Dhaka. Circular river systems and flood embankment likely facilitate transmission
      of infectious V. cholerae throughout the year that leads to both sudden and off
      season outbreaks in the densely populated urban ecosystem of Dhaka. Clonal
      recycling of hybrid El Tor with increasing virulence in a changing climate and in
      a region with a growing urban population represents a serious public health
      concern for Bangladesh.

PMID- 22957116
TI  - Migratory birds, ticks, and Bartonella.
AB  - Bartonella spp. infections are considered to be vector-borne zoonoses; ticks are
      suspected vectors of bartonellae. Migratory birds can disperse ticks infected
      with zoonotic pathogens such as Rickettsia and tick-borne encephalitis virus and
      possibly also Bartonella. Thus, in the present study 386 tick specimens collected
      in spring 2009 from migratory birds on the Mediterranean islands Capri and
      Antikythera were screened for Bartonella spp. RNA. One or more ticks were found
      on 2.7% of the birds. Most ticks were Hyalomma rufipes nymphs and larvae with
      mean infestation rates of 1.7 nymphs and 0.6 larvae per infested bird. Bartonella
      spp. RNA was not detected in any of the tick specimens.

PMID- 22957117
TI  - Enterococcus faecium coisolated with Lactobacillus species can mimic vancomycin
      resistant enterococci.

PMID- 22957118
TI  - One health national programme across species on zoonoses: a call to the
      developing world.
AB  - Zoonoses constitute 868 (61%) of all known infectious diseases, 75% of the
      infections considered 'emerging' are zoonoses. Developed nations have national
      programmes, adjoining "One Health" concept to combat zoonoses, whereas
      inadequacies exist in developing nations. As a case study, role of national
      programmes in India, a developing nation with a large human and animal
      population, was explored, as we did have acquaintance of it. Data from PubMed was
      extracted using keywords "Zoonoses AND Prevalence/Incidence AND India AND Human
      OR Animal" till 2009. Additionally, some individual disease keywords were used
      for extraction, which were missed by the above comprehensive search terms. On
      appraisal, the health sector in India has only a few national programme on
      zoonoses where as none exists in animal husbandry sector. In the struggle against
      zoonoses -a major constituent of emerging infections, a system approach based,
      one national programme is urgently required for the developing world.

PMID- 22957119
TI  - First documented case of a Staphylococcus lugdunensis strain carrying the mecA
      gene in Northern Europe.
AB  - Staphylococcus lugdunensis is a clinically common wound pathogen belonging to
      coagulase-negative staphylococci. We herein report the first case of a S.
      lugdunensis isolate carrying the mecA gene in Northern Europe.

PMID- 22957120
TI  - Prevalence of hepatitis E virus antibodies in pigs in Northern Italy.
AB  - The prevalence of the hepatitis E virus (HEV) infection in pigs in Northern Italy
      was serologically examined. The survey was carried out on 39 farms: 17 farrow-to
      feeder, 10 farrow-to-finish, and 12 fattening enterprises. There were 1,422 sera
      that were tested using commercial indirect ELISA. This method originally
      developed for testing human sera was adapted for the analysis of pig sera. All
      farms except one (97.43%) and 714 sera samples (50.21%) resulted positive for
      anti-HEV IgG antibodies. This study confirms that HEV is widespread in pigs in
      Italy and might be endemic on most farms.

PMID- 22957121
TI  - The need for one health degree programs.
AB  - This commentary offers suggestions for improving public health and public health
      education by emphasizing One Health principles, the integrating of human,
      veterinary, and environmental sciences. One Health is increasingly recognized as
      a powerful approach to the prevention and control of zoonotic diseases,
      increasing food productivity and safety, improving biosecurity, and enhancing
      many areas of biomedical research.

PMID- 22957122
TI  - Inaugural editorial.

PMID- 22957123
TI  - Extended spectrum beta-lactamases detected in Escherichia coli from gulls in
      Stockholm, Sweden.
AB  - In order to investigate if bacterial antibiotic resistance was present in gull
      populations in urbanised areas, we conducted a study in which faecal samples from
      gulls were collected in central Stockholm, Sweden in April and May 2010 and
      screened for extended spectrum beta-lactamases (ESBL)-type antibiotic resistance.
      Eighteen of 194 randomly selected Escherichia coli isolates harboured ESBL of CTX
      M phenotype. Since the bacteria are unlikely to have developed the resistance in
      gulls, it may indicate leakage of resistant bacteria to the environment. As many
      gulls find food and shelter in cities around the world and thereby share their
      habitat with dense human populations, the finding that as many as 9% of gulls
      carry ESBL-type antibiotic resistance may imply that zoonotic transmission
      between gulls, humans, and other animals is likely to occur in such places. This
      study illustrates how ecologically widespread the problem of antibiotic
      resistance has become and this has implications for future policy making to
      reduce the spread of bacteria with antibiotic resistance.

PMID- 22957124
TI  - Oseltamivir (Tamiflu((r))) in the environment, resistance development in
      influenza A viruses of dabbling ducks and the risk of transmission of an
      oseltamivir-resistant virus to humans - a review.
AB  - The antiviral drug oseltamivir (Tamiflu((r))) is a cornerstone in influenza
      pandemic preparedness plans worldwide. However, resistance to the drug is a
      growing concern. The active metabolite oseltamivir carboxylate (OC) is not
      degraded in surface water or sewage treatment plants and has been detected in
      river water during seasonal influenza outbreaks. The natural influenza reservoir,
      dabbling ducks, can thus be exposed to OC in aquatic environments. Environmental
      like levels of OC induce resistance development in influenza A/H1N1 virus in
      mallards. There is a risk of resistance accumulation in influenza viruses
      circulating among wild birds when oseltamivir is used extensively. By
      reassortment or direct transmission, oseltamivir resistance can be transmitted to
      humans potentially causing a resistant pandemic or human-adapted highly
      pathogenic avian influenza virus. There is a need for more research on resistance
      development in the natural influenza reservoir and for a prudent use of
      antivirals.

PMID- 22957125
TI  - Antimicrobial activity of filamentous fungi isolated from highly antibiotic
      contaminated river sediment.
AB  - BACKGROUND: Filamentous fungi are well known for their production of substances
      with antimicrobial activities, several of which have formed the basis for the
      development of new clinically important antimicrobial agents. Recently,
      environments polluted with extraordinarily high levels of antibiotics have been
      documented, leading to strong selection pressure on local sentinel bacterial
      communities. In such microbial ecosystems, where multidrug-resistant bacteria are
      likely to thrive, it is possible that certain fungal antibiotics have become less
      efficient, thus encouraging alternative strategies for fungi to compete with
      bacteria. METHODS: In this study, sediment of a highly antibiotic-contaminated
      Indian river was sampled in order to investigate the presence of cultivable
      filamentous fungi and their ability to produce substances with antimicrobial
      activity. RESULTS: Sixty one strains of filamentous fungi, predominantly various
      Aspergillus spp. were identified. The majority of the Aspergillus strains
      displayed antimicrobial activity against methicillin-resistant Staphylococcus
      aureus, extended-spectrum beta-lactamase-producing Escherichia coli, vancomycin
      resistant Enterococcus faecalis and Candida albicans. Bioassay-guided isolation
      of the secondary metabolites of A. fumigatus led to the identification of
      gliotoxin. CONCLUSION: This study demonstrated proof of principle of using
      bioassay-guided isolation for finding bioactive molecules.

PMID- 22957126
TI  - Antibiotic resistance - why is the problem so difficult to solve?
AB  - Antibiotic resistance has been increasing along with antibiotic use. At the same
      time, the supply of new drugs to replace those rendered inefficient by the
      development has been dwindling, leading to concerns that we may soon lack
      efficient means to treat bacterial infections. Though the problem has received
      considerable interest, there are no indications that the situation is about to
      change. The present review maintains that this is because the two objectives -
      preserving the efficiency of existing drugs and increasing the supply of new ones
      - are partly opposing. Hence, creating an incentive structure compatible with
      both of them is not easy. Nevertheless, it is suggested that levying a fee on the
      use of antibiotics, and earmarking the proceeds from this fee for subsidizing
      development of new antibiotics, would be an important step towards increasing
      incentives for a better antibiotic stewardship while preserving incentives to
      develop new substances.

PMID- 22957127
TI  - Experimental infection of three laboratory mouse stocks with a shrew origin
      Bartonella elizabethae strain: an evaluation of bacterial host switching
      potential.
AB  - BACKGROUND: Bartonella elizabethae has been reported as a causative agent of
      human illnesses and strains of this bacterium are commonly isolated from
      commensal small mammals in Asia. METHODS: Since the zoonotic potential of a
      pathogen is often related to its host switching ability, we explored the capacity
      of a B. elizabethae strain to host switch by subcutaneously inoculating groups of
      Swiss Webster, BALB/c, and C57BL/6 mice with the bacteria at a range of doses.
      RESULTS: A low number of mice in each of the three groups showed susceptibility
      to infection at high doses (10(5) and 10(6) bacteria), and developed bacteremias
      of 6-8 weeks duration. CONCLUSION: The capacity of this B. elizabethae strain to
      switch hosts can have important public health consequences for humans in areas of
      Asia where many small mammal populations have high bartonellae infection
      prevalences and live as commensals with humans.

PMID- 22957128
TI  - Chlamydia psittaci in birds of prey, Sweden.
AB  - BACKGROUND: Chlamydia psittaci is an intracellular bacterium primarily causing
      respiratory diseases in birds but may also be transmitted to other animals,
      including humans. The prevalence of the pathogen in wild birds in Sweden is
      largely unknown. METHODS: DNA was extracted from cloacae swabs and screened for
      C. psittaci by using a 23S rRNA gene PCR assay. Partial 16S rRNA and ompA gene
      fragments were sequence determined and phylogenies were analysed by the neighbour
      joining method. RESULTS AND CONCLUSION: The C. psittaci prevalence was 1.3% in
      319 Peregrine Falcons and White-tailed Sea Eagles, vulnerable top-predators in
      Sweden. 16S rRNA and ompA gene analysis showed that novel Chlamydia species, as
      well as novel C. psittaci strains, are to be found among wild birds.

PMID- 22957129
TI  - Rodent-borne diseases in Thailand: targeting rodent carriers and risky habitats.
AB  - BACKGROUND: Comparative analysis, which aims at investigating ecological and
      evolutionary patterns among species, may help at targeting reservoirs of zoonotic
      diseases particularly in countries presenting high biodiversity. Here, we
      developed a simple method to target rodent reservoirs using published studies
      screening microparasite infections. METHODS: We compiled surveys of
      microparasites investigated in rodents trapped in Thailand. The data comprise a
      total of 17,358 rodents from 18 species that have been investigated for a total
      of 10 microparasites (viruses, bacteria and protozoans). We used residual
      variation of microparasite richness controlled for both rodent sample size and
      pathogens' screening effort to identify major rodent reservoirs and potential
      risky habitats. RESULTS: Microparasite species richness was positively related to
      rodent sample size and pathogens' screening effort. The investigation of the
      residual variations of microparasite species richness showed that several rodent
      species harboured more pathogens than expected by the regression model.
      Similarly, higher pathogen richness than expected was observed in rodents living
      in non-flooded lands, forests and paddy fields. CONCLUSION: Our results suggest
      to target some rodent species that are not commonly investigated for pathogen
      screening or surveillance such as R. adamanensis or B. savilei, and that non
      flooded lands and forests should be more taken into caution, whereas much surveys
      focused on paddy rice fields and households.

PMID- 22957130
TI  - Rodents on pig and chicken farms - a potential threat to human and animal health.
AB  - Rodents can cause major problems through spreading various diseases to animals
      and humans. The two main species of rodents most commonly found on farms around
      the world are the house mouse (Mus musculus) and the brown rat (Rattus
      norvegicus). Both species are omnivorous and can breed year-round under
      favourable conditions. This review describes the occurrence of pathogens in
      rodents on specialist pig and chicken farms, which are usually closed units with
      a high level of bio-security. However, wild rodents may be difficult to exclude
      completely, even from these sites, and can pose a risk of introducing and
      spreading pathogens. This article reviews current knowledge regarding rodents as
      a hazard for spreading disease on farms. Most literature available regards
      zoonotic pathogens, while the literature regarding pathogens that cause disease
      in farm animals is more limited.

PMID- 22957131
TI  - Vancomycin resistant enterococci in farm animals - occurrence and importance.
AB  - The view on enterococci has over the years shifted from harmless commensals to
      opportunistic but important pathogens mainly causing nosocomial infections. One
      important part of this development is the emergence of vancomycin resistance
      enterococci (VRE). The term VRE includes several combinations of bacterial
      species and resistance genes of which the most clinically important is
      Enterococcus faecium with vanA type vancomycin resistance. This variant is also
      the most common VRE among farm animals. The reason for VRE being present among
      farm animals is selection by extensive use of the vancomycin analog avoparcin for
      growth promotion. Once the use of avoparcin was discontinued, the prevalence of
      VRE among farm animals decreased. However, VRE are still present among farm
      animals and by spread via food products they could potentially have a negative
      impact on public health. This review is based on the PhD thesis Vancomycin
      Resistant Enterococci in Swedish Broilers - Emergence, Epidemiology and
      Elimination and makes a short summary of VRE in humans and food producing
      animals. The specific situation regarding VRE in Swedish broiler production is
      also mentioned.

PMID- 22957132
TI  - How often do they meet? Genetic similarity between European populations of a
      potential disease vector Culex pipiens.
AB  - BACKGROUND: Species in the Culex pipiens complex are common almost all over the
      world and represent important vectors for many serious zoonotic diseases. Even
      if, at the moment, many of the pathogens potentially transmitted by Cx. pipiens
      are not a problem in northern Europe, they may, with increasing temperatures and
      changing ecosystems caused by climate change, move northward in the future.
      Therefore, the question whether or not the Cx. pipiens populations in northern
      Europe will be competent vectors for them is of high importance. One way to
      estimate the similarity and the rate of contact between European Cx. pipiens
      populations is to look at the gene exchange between these populations. METHODS:
      To test the genetic diversity and degree of differentiation between European Cx.
      pipiens populations, we used eight microsatellite markers in 10 mosquito
      populations originating from northern, central, and southern Europe. RESULTS: We
      found that three of the analyzed populations were very different from the rest of
      the populations and they also greatly differed from each other. When these three
      populations were removed, the variance among the rest of the populations was low,
      suggesting an extensive historic gene flow between many European Cx. pipiens
      populations. CONCLUSIONS: This suggests that infectious diseases spread by this
      species may not be associated with a certain vector genotype but rather with
      suitable environmental conditions. Consequently, we would expect these pathogens
      to disperse northward with favorable climatic parameters.

PMID- 22957133
TI  - Co-infection rate of HIV, HBV and Syphilis among HCV seropositive identified
      blood donors in Kathmandu, Nepal.
AB  - BACKGROUND: HIV, HBV, Syphilis and HCV share common modes of transmission.
      OBJECTIVE: The study was aimed to determine the co-infection rate of HIV, HBV and
      Syphilis among HCV seropositive identified blood donors. METHODS: The study was
      conducted on blood samples screened as HCV seropositive at Nepal Red Cross
      Society, Central Blood Transfusion Service, Kathmandu, Nepal. HCV seropositive
      samples were further tested for HIV, HBV and Syphilis. RESULTS: Eight co
      infections were observed in 139 HCV seropositives with total co-infection rate of
      5.75% (95% CI=2.52-11.03). CONCLUSION: Co-infection of HIV, HBV and Syphilis with
      HCV is prevalent in the healthy looking blood donors of Kathmandu, Nepal.

PMID- 22957135
TI  - A longitudinal study of antimicrobial resistant faecal bacteria in sediments
      collected from a hospital wastewater system.
AB  - OBJECTIVE: The objective with this study was to determine and follow
      antimicrobial resistance in faecal bacteria over time in hospital wastewater pipe
      sediment. A further aim was to determine bacterial growth rates of sensitive,
      intermediate and resistant intestinal enterococci in different ciprofloxacin
      concentrations as a measure of bacterial fitness. METHODS: A system enabling the
      collection of settled particles over time was installed at Kalmar County
      Hospital. Samples were collected bi-monthly for a 14-month period. Coliform
      bacteria and enterococci were isolated from the sediment with standard methods
      and investigated for resistance to ciprofloxacin (CIP), imipenem (IMI),
      trimetroprim-sulfamethoxazole (TS), ampicillin (AMP) and vancomycin (VAN) by the
      disc diffusion method. Resistant isolates were further typed with the
      PhenePlateTM system. Growth assessments were performed with an automated
      spectrophotometer. RESULTS: The rate of intestinal enterococci resistance was
      <0.6, 1.3, 1.9 and 13% to VAN, IMI, AMP and CIP respectively. Coliform resistance
      frequencies were 1.1, 2.2 and 2.2% to CIP, IMI and TS respectively. At two
      sampling occasions, significantly higher rates of ciprofloxacin resistant
      enterococci were found and the establishment of a resistant clone in the sewer
      was indicated by the PhP-analysis. Ciprofloxacin resistant intestinal enterococci
      had a significantly longer lag-phase time than sensitive isolates, but from 500
      ug ml(-1) (half MIC) resistant isolates had a competitive advantage in terms of
      significantly faster generation time. DISCUSSION: Despite high concentration of
      antimicrobials in the sediment, resistance frequencies were generally low. This
      can depend on limited growth possibilities for faecal bacteria. However, the
      establishment of a resistant clone shows that hospital sewers can serve as a
      reservoir for antibiotic resistant bacteria.

PMID- 22957134
TI  - Threats from emerging and re-emerging neglected tropical diseases (NTDs).
AB  - BACKGROUND: Neglected tropical diseases impact over 1 billion of the world's
      poorest populations and require special attention. However, within the NTDs
      recognized by the World Health Organization, some are also dually categorized as
      emerging and re-emerging infectious diseases requiring more detailed examination
      on potential global health risks. METHODS: We reviewed the 17 NTDs classified by
      the WHO to determine if those NTDs were also categorized by the US Centers for
      Disease Control and Prevention as emerging and re-emerging infectious diseases
      (''EReNTDs''). We then identified common characteristics and risks associated
      with EReNTDs. RESULTS: Identified EReNTDs of dengue, rabies, Chagas Disease, and
      cysticercosis disproportionately impact resource-poor settings with poor social
      determinants of health, spread through globalization, are impacted by vector
      control, lack available treatments, and threaten global health security. This
      traditionally neglected subset of diseases requires urgent attention and unique
      incentive structures to encourage investment in innovation and coordination.
      DISCUSSION: Multi-sectorial efforts and targeted public-private partnerships
      would spur needed R&D for effective and accessible EReNTD treatments, improvement
      of social determinants of health, crucial low-income country development, and
      health system strengthening efforts. Utilization of One Health principles is
      essential for enhancing knowledge to efficaciously address public health aspects
      of these EReNTDs globally.

PMID- 22957136
TI  - A novel Salmonella serovar isolated from Peregrine Falcon (Falco peregrinus)
      nestlings in Sweden: Salmonella enterica enterica serovar Pajala (Salmonella
      Pajala).
AB  - A novel Salmonella serovar was isolated from Peregrine falcon (Falco peregrinus)
      nestlings in northern Sweden in 2006. Three isolates of the same clone was
      retrieved from three falcon siblings and characterized as Salmonella enterica sub
      species enterica: O-phase 13, 23:-: e, n, z 15 and the H-phase was not present.
      We propose the geographical name Salmonella enterica, sub-species enterica
      serovar Pajala to this novel Salmonella.

PMID- 22957137
TI  - Adaptation to flooding during emergence and seedling growth in rice and weeds,
      and implications for crop establishment.
AB  - BACKGROUND AND AIMS: Direct seeding of rice is being adopted in rainfed and
      irrigated lowland ecosystems because it reduces labour costs in addition to other
      benefits. However, early flooding due to uneven fields or rainfall slows down
      seed germination and hinders crop establishment. Conversely, early flooding helps
      suppress weeds and reduces the costs of manual weeding and/or dependence on
      herbicides; however, numerous weed species are adapted to lowlands and present
      challenges for the use of flooding to control weeds. Advancing knowledge on the
      mechanisms of tolerance of flooding during germination and early growth in rice
      and weeds could facilitate the development of improved rice varieties and
      effective weed management practices for direct-seeded rice. PRINCIPAL RESULTS:
      Rice genotypes with a greater ability to germinate and establish in flooded soils
      were identified, providing opportunities to develop varieties suitable for direct
      seeding in flooded soils. Tolerance of flooding in these genotypes was mostly
      attributed to traits associated with better ability to mobilize stored
      carbohydrates and anaerobic metabolism. Limited studies were undertaken in weeds
      associated with lowland rice systems. Remaining studies compared rice and weeds
      and related weed species such as Echinochloa crus-galli and E. colona or compared
      ecotypes of the same species of Cyperus rotundus adapted to either aerobic or
      flooded soils. CONCLUSIONS: Tolerant weeds and rice genotypes mostly developed
      similar adaptive traits that allow them to establish in flooded fields, including
      the ability to germinate and elongate faster under hypoxia, mobilize stored
      starch reserves and generate energy through fermentation pathways. Remarkably,
      some weeds developed additional traits such as larger storage tubers that enlarge
      further in deeper flooded soils (C. rotundus). Unravelling the mechanisms
      involved in adaptation to flooding will help design management options that will
      allow tolerant rice genotypes to adequately establish in flooded soils while
      simultaneously suppressing weeds.

PMID- 22957138
TI  - Effects of the CACNA1C risk allele on neurocognition in patients with
      schizophrenia and healthy individuals.
AB  - Recent genetic association studies have identified the A-allele of rs1006737
      within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some
      evidence suggests that this polymorphism plays a role in cognitive function both
      in schizophrenia patients and healthy individuals; however, the precise nature of
      this association remains unclear. Here we investigated the possible association
      of this polymorphism with a wide range of neurocognitive functions in
      schizophrenia patients and in healthy subjects. Schizophrenia patients exhibited
      significantly poorer performance on all the cognitive domains as compared to
      healthy controls. In patients, A-allele carriers demonstrated significantly worse
      logical memory performance than the G-allele homozygotes. In controls, no
      significant association was observed between the genotype and any of the
      cognitive domains examined. These results add to the literature suggesting that
      rs1006737 may be associated with schizophrenia through its detrimental effect on
      endophenotypic traits.

PMID- 22957140
TI  - Targeting the cancer cell cycle by cold atmospheric plasma.
AB  - Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at
      low temperatures, is currently being evaluated as a new highly selective
      alternative addition to existing cancer therapies. Here, we present a first
      attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold
      G2/M increase in two different types of cancer cells with different degrees of
      tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to
      CAP treatment is caused by differences in the distribution of cancer cells and
      normal cells within the cell cycle. The expression of gammaH2A.X (pSer139), an
      oxidative stress reporter indicating S-phase damage, is enhanced specifically
      within CAP treated cells in the S phase of the cell cycle. Together with a
      significant decrease in EdU-incorporation after CAP, these data suggest that
      tumorigenic cancer cells are more susceptible to CAP treatment.

PMID- 22957139
TI  - Rapid identification and drug susceptibility screening of ESAT-6 secreting
      Mycobacteria by a NanoELIwell assay.
AB  - To meet the global needs of tuberculosis (TB) control, a nanoELIwell device was
      developed as a multifunctional assay for TB diagnosis and drug susceptibility
      testing. The device integrates on-chip culturing of mycobacteria, immunoassay,
      and high-resolution fluorescent imaging. Mycobacterium smegmatis and
      Mycobacterium kansasii were used as models of Mycobacterium tuberculosis to
      evaluate device integrity by using antigens, Ag85 and ESAT-6, as biomarkers. As a
      result, the nanoELIwell device detected antigens released from a single bacterium
      within 24-48-hour culture. Antimycobacterial drug-treated M. smegmatis showed
      significant decreased in Ag85 antigen production when treated with ethambutol and
      no change in antigen production when treated with rifampin, demonstrating drug
      susceptibility and resistance, respectively. The nanoELIwell assay also
      distinguished the ESAT-6-secreting M. kansasii from the non-ESAT-6-secreting M.
      simiae. The combination of microwell technology and ELISA assay holds potential
      to the development of a rapid, sensitive, and specific diagnostics and
      susceptibility testing of TB.

PMID- 22957141
TI  - Silencing of microRNA-122 enhances interferon-alpha signaling in the liver
      through regulating SOCS3 promoter methylation.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease
      worldwide. Although novel drugs against HCV are under development, the current
      standard therapy consists principally of interferon (IFN). To improve the
      response to IFN treatment by enhancing interferon-stimulated response element
      (ISRE)-mediated gene transcription, we screened 75 microRNAs highly expressed in
      hepatocytes for their ability to modulate ISRE activity. Overexpression of
      microRNA-122 (miR122) significantly suppressed ISRE activity. Conversely,
      silencing of miR122 function enhanced IFN-induced ISRE activity, by decreasing
      expression of suppressor of cytokine signaling 3 (SOCS3). This decrease in SOCS3
      level was not mediated by microRNA target gene suppression, but rather by
      enhanced methylation at SOCS3 gene promoter. Taken together, our data, along with
      the fact that antisense oligonucleotides of miR122 also directly inhibit HCV
      replication, suggest that a combination therapy comprising IFN and silencing of
      miR122 function may be a promising therapeutic option in the near future.

PMID- 22957143
TI  - Complex genetic patterns in closely related colonizing invasive species.
AB  - Anthropogenic activities frequently result in both rapidly changing environments
      and translocation of species from their native ranges (i.e., biological
      invasions). Empirical studies suggest that many factors associated with these
      changes can lead to complex genetic patterns, particularly among invasive
      populations. However, genetic complexities and factors responsible for them
      remain uncharacterized in many cases. Here, we explore these issues in the vase
      tunicate Ciona intestinalis (Ascidiacea: Enterogona: Cionidae), a model species
      complex, of which spA and spB are rapidly spreading worldwide. We intensively
      sampled 26 sites (N = 873) from both coasts of North America, and performed
      phylogenetic and population genetics analyses based on one mitochondrial fragment
      (cytochrome c oxidase subunit 3-NADH dehydrogenase subunit I, COX3-ND1) and eight
      nuclear microsatellites. Our analyses revealed extremely complex genetic patterns
      in both species on both coasts. We detected a contrasting pattern based on the
      mitochondrial marker: two major genetic groups in C. intestinalis spA on the west
      coast versus no significant geographic structure in C. intestinalis spB on the
      east coast. For both species, geo-graphically distant populations often showed
      high microsatellite-based genetic affinities whereas neighboring ones often did
      not. In addition, mitochondrial and nuclear markers provided largely inconsistent
      genetic patterns. Multiple factors, including random genetic drift associated
      with demographic changes, rapid selection due to strong local adaptation, and
      varying propensity for human-mediated propagule dispersal could be responsible
      for the observed genetic complexities.

PMID- 22957142
TI  - Self-limited versus delayed resolution of acute inflammation: temporal regulation
      of pro-resolving mediators and microRNA.
AB  - Mechanisms underlying delays in resolution programs of inflammation are of
      interest for many diseases. Here, we addressed delayed resolution of inflammation
      and identified specific microRNA (miR)-metabolipidomic signatures. Delayed
      resolution initiated by high-dose challenges decreased miR-219-5p expression
      along with increased leukotriene B(4) (5-fold) and decreased (~3-fold)
      specialized pro-resolving mediators, e.g. protectin D1. Resolvin (Rv)E1 and RvD1
      (1 nM) reduced miR-219-5p in human macrophages, not shared by RvD2 or PD1. Since
      mature miR-219-5p is produced from pre-miRs miR-219-1 and miR-219-2, we co
      expressed in human macrophages a 5-lipoxygenase (LOX) 3'UTR-luciferase reporter
      vector together with either miR-219-1 or miR-219-2. Only miR-219-2 reduced
      luciferase activity. Apoptotic neutrophils administered into inflamed exudates in
      vivo increased miR-219-2-3p expression and PD1/NPD1 levels as well as decreased
      leukotriene B(4). These results demonstrate that delayed resolution undermines
      endogenous resolution programs, altering miR-219-2 expression, increasing pro
      inflammatory mediators and compromising SPM production that contribute to failed
      catabasis and homeostasis.

PMID- 22957144
TI  - Influence of dietary specialization and resource availability on geographical
      variation in abundance of butterflyfish.
AB  - Empirical evidence indicates that both niche breadth and resource availability
      are key drivers of a species' local abundance patterns. However, most studies
      have considered the influence of either niche breath or resource availability in
      isolation, while it is the interactive effects that are likely to influence local
      abundance. We examined geographic variation in the feeding ecology and
      distribution of coral-feeding butterflyfish to determine the influence of dietary
      specialization and dietary resource availability on their local abundance.
      Dietary composition and abundance of five butterflyfish and coral dietary
      resource availability were determined at 45 sites across five locations (Lizard
      Island and Heron Island, Great Barrier Reef; Kimbe Bay, Papua New Guinea; Noumea,
      New Caledonia; and Moorea, French Polynesia). Multiple regression models using
      variables representative of total dietary resource availability, availability of
      specific dietary resources, and interspecific competition were used to determine
      the best predictors of local abundance across all sites and locations for each
      species. Factors influencing local abundance varied between butterflyfish with
      specialized and generalized diets. Dietary resource availability had the
      strongest influence on the abundance of Chaetodon trifascialis-the most
      specialized species. Local abundance of C. trifascialis was best predicted by
      availability of the Acropora corals that it preferentially feeds on. In contrast,
      abundance of generalist butterflyfish was poorly described by variation in
      availability of specific resources. Rather, indices of total dietary resource
      availability best predicted their abundance. Overall, multiple regression models
      only explained a small proportion of the variation in local abundance for all
      five species. Despite their relatively specialized diets, dietary resource
      availability has limited influence on the local abundance of butterflyfish. Only
      the most specialized species appear to be consistently limited by prey
      availability. Local and total abundance of species are influenced by a wide range
      of different factors and there is definite need to conduct independent species
      assessments.

PMID- 22957145
TI  - Sex-specific effects of developmental environment on reproductive trait
      expression in Drosophila melanogaster.
AB  - Variation in the expression of reproductive traits provides the raw material upon
      which sexual selection can act. It is therefore important to understand how key
      factors such as environmental variation influence the expression of reproductive
      traits, as these will have a fundamental effect on the evolution of mating
      systems. It is also important to consider the effects of environmental variation
      upon reproductive traits in both sexes and to make comparisons with the
      environment to which the organism is adapted. In this study, we addressed these
      issues in a systematic study of the effect of a key environmental factor,
      variation in larval density, on reproductive trait expression in male and female
      Drosophila melanogaster. To do this, we compared reproductive trait expression
      when flies were reared under controlled conditions at eight different larval
      densities that covered a 20-fold range. Then, to place these results in a
      relevant context, we compared the results to those from flies sourced directly
      from stock cages. Many reproductive traits were surprisingly insensitive to
      variation in larval density. A notable exception was nonlinear variation in
      female fecundity. In contrast, we found much bigger differences in comparisons
      with flies from stock cages-including differences in body size, latency to mate,
      copulation duration, fecundity, and male share of paternity in a competitive
      environment. For a number of traits, even densities of 1000 larvae per vial (125
      larvae per mL of food) did not phenocopy stock cage individuals. This study
      reveals novel patterns of sex-specific sensitivity to environmental variation
      that will influence the strength of sexual selection. It also illustrates the
      importance of comparisons with the environment to which individuals are adapted.

PMID- 22957146
TI  - Evolution of a sexually dimorphic trait in a broadly distributed topminnow
      (Fundulus olivaceus).
AB  - Understanding the interaction between sexual and natural selection within
      variable environments is crucial to our understanding of evolutionary processes.
      The handicap principle predicts females will prefer males with exaggerated traits
      provided those traits are indicators of male quality to ensure direct or indirect
      female benefits. Spatial variability in ecological factors is expected to alter
      the balance between sexual and natural selection that defines the evolution of
      such traits. Male and female blackspotted topminnows (Fundulidae: Fundulus
      olivaceus) display prominent black dorsolateral spots that are variable in number
      across its broad range. We investigated variability in spot phenotypes at 117
      sites across 13 river systems and asked if the trait was sexually dimorphic and
      positively correlated with measures of fitness (condition and gonadosomatic index
      [GSI]). Laboratory and mesocosm experiments assessed female mate choice and
      predation pressure on spot phenotypes. Environmental and community data collected
      at sampling locations were used to assess predictive models of spot density at
      the individual, site, and river system level. Greater number of spots was
      positively correlated with measures of fitness in males. Males with more spots
      were preferred by females and suffered greater mortality due to predation. Water
      clarity (turbidity) was the best predictor of spot density on the drainage scale,
      indicating that sexual and natural selection for the trait may be mediated by
      local light environments.

PMID- 22957147
TI  - Understanding of the impact of chemicals on amphibians: a meta-analytic review.
AB  - Many studies have assessed the impact of different pollutants on amphibians
      across a variety of experimental venues (laboratory, mesocosm, and enclosure
      conditions). Past reviews, using vote-counting methods, have described pollution
      as one of the major threats faced by amphibians. However, vote-counting methods
      lack strong statistical power, do not permit one to determine the magnitudes of
      effects, and do not compare responses among predefined groups. To address these
      challenges, we conducted a meta-analysis of experimental studies that measured
      the effects of different chemical pollutants (nitrogenous and phosphorous
      compounds, pesticides, road deicers, heavy metals, and other wastewater
      contaminants) at environmentally relevant concentrations on amphibian survival,
      mass, time to hatching, time to metamorphosis, and frequency of abnormalities.
      The overall effect size of pollutant exposure was a medium decrease in amphibian
      survival and mass and a large increase in abnormality frequency. This translates
      to a 14.3% decrease in survival, a 7.5% decrease in mass, and a 535% increase in
      abnormality frequency across all studies. In contrast, we found no overall effect
      of pollutants on time to hatching and time to metamorphosis. We also found that
      effect sizes differed among experimental venues and among types of pollutants,
      but we only detected weak differences among amphibian families. These results
      suggest that variation in sensitivity to contaminants is generally independent of
      phylogeny. Some publication bias (i.e., selective reporting) was detected, but
      only for mass and the interaction effect size among stressors. We conclude that
      the overall impact of pollution on amphibians is moderately to largely negative.
      This implies that pollutants at environmentally relevant concentrations pose an
      important threat to amphibians and may play a role in their present global
      decline.

PMID- 22957148
TI  - Infectious disease in animal metapopulations: the importance of environmental
      transmission.
AB  - Motivated by an array of infectious diseases that threaten wildlife populations,
      a simple metapopulation model (subpopulations connected by animal movement) is
      developed, which allows for both movement-based and environmental transmission.
      The model demonstrates that for a range of plausible parameterizations of
      environmental transmission, increased movement rate of animals between discrete
      habitats can lead to a decrease in the overall proportion of sites that are
      occupied. This can limit the ability of the rescue effect to ensure locally
      extinct populations become recolonized and can drive metapopulations down in size
      so that extinction by mechanisms other than disease may become more likely. It
      further highlights that, in the context of environmental transmission, the
      environmental persistence time of pathogens and the probability of acquiring
      infection by environmental transmission can affect host metapopulations both
      qualitatively and quantitatively. Additional spillover sources of infection from
      alternate reservoir hosts are also included in the model and a synthesis of all
      three types of transmission, acting alone or in combination, is performed
      revealing that movement-based transmission is the only necessary condition for a
      decline in the proportion of occupied sites with increasing movement rate, but
      that the presence of other types of transmission can reverse this qualitative
      result. By including the previously neglected role of environmental transmission,
      this work contributes to the general discussion of when dispersal by wild animals
      is beneficial or detrimental to populations experiencing infectious disease.

PMID- 22957149
TI  - Consequences of changing rainfall for fungal pathogen-induced mortality in
      tropical tree seedlings.
AB  - Most general circulation models predict that most tropical forests will
      experience lower and less frequent rainfall in future as a result of climate
      change, which may reduce the capacity of fungal pathogens to drive density
      dependent tree mortality. This is potentially significant because fungal
      pathogens are thought to play a key role in promoting and structuring plant
      diversity in tropical forests through the Janzen-Connell mechanism. Therefore, we
      hypothesize that the drying of tropical forests will negatively impact species
      coexistence. To test one prediction of this hypothesis, we imposed experimental
      watering regimes on the seedlings of a tropical tree, Pleradenophora longicuspis,
      and measured mortality induced by fungal pathogens under shade house conditions.
      The frequency of watering had a strong impact on survival. Seedlings watered
      daily experienced significantly higher mortality than those watered every three
      or every six days, while increasing the volume of water applied also led to
      increased mortality, although this relationship was less pronounced. These
      results suggest that the capacity of fungal pathogens to drive density-dependent
      mortality may be reduced in drier climates and when rainfall is less frequent,
      with potential implications for the diversity enhancing Janzen-Connell mechanism.

PMID- 22957150
TI  - The effects of reproductive specialization on energy costs and fitness genetic
      variances in cyclical and obligate parthenogenetic aphids.
AB  - Organisms with coexisting sexual and asexual populations are ideal models for
      studying the consequences of either reproductive mode on the quantitative genetic
      architecture of life-history traits. In the aphid Rhopalosiphum padi, lineages
      differing in their sex investment coexist but all share a common parthenogenetic
      phase. Here, we studied multiple genotypes of R. padi specialized either for
      sexual and asexual reproduction and compared their genetic variation in fitness
      during the parthenogenetic phase. Specifically, we estimated maintenance costs as
      standard metabolic rate (SMR), together with fitness (measured as the intrinsic
      rate of increase and the net reproductive rate). We found that genetic variation
      (in terms of broad-sense heritability) in fitness was higher in asexual genotypes
      compared with sexual genotypes. Also, we found that asexual genotypes exhibited
      several positive genetic correlations indicating that body mass, whole-animal
      SMR, and apterous individuals production are contributing to fitness. Hence, it
      appears that in asexual genotypes, energy is fully allocated to maximize the
      production of parthenogenetic individuals, the simplest possible form of aphid
      repertoire of life-histories strategies.

PMID- 22957151
TI  - Female teneral mating in a monandrous species.
AB  - Schultesia nitor is a gregarious species living in Cacicus and Psarocolius ssp.
      pouch-like nests. Due to gregariousness, opportunities for multiple copulations
      in both sexes are not supposed to be restricted. Females produce only one brood
      during their life and die within a few days following the birth of their nymphs,
      but this unique brood could be the result of either single or multiple mating
      events (i.e., monandry vs. polyandry). In this study, we first determined the age
      of sexual receptivity of both males and females. Larval development in this
      species is shorter in males than in females and thus, this species is protandric.
      Males were not able to copulate the day after emergence. Contrary to males,
      teneral females (i.e., females achieving their imaginal molt but not yet fully
      sclerotised and colored) were attractive and were able to mate with males. In the
      second experiment, we tested the existence of multiple matings in both sexes. Our
      results showed that females were monandrous whereas males were polygynous. Since
      we had observed that females were monoandrous, we expected them to be choosy and
      we determined their ability to discriminate between virgin and nonvirgin males.
      When given the choice, females preferred virgin males and overall, they were more
      successful at mating than experienced ones. Our results suggest that monandry may
      be primarily driven by the female's short life-span fecundity. The occurrence of
      teneral mating in this species calls into question the existence of a male
      strategy for monopolizing females, and as well as the implication of female
      choice. Although further work is required, this species provides an interesting
      model for understanding sexual conflicts.

PMID- 22957152
TI  - Introduction pathway and climate trump ecology and life history as predictors of
      establishment success in alien frogs and toads.
AB  - A major goal for ecology and evolution is to understand how abiotic and biotic
      factors shape patterns of biological diversity. Here, we show that variation in
      establishment success of nonnative frogs and toads is primarily explained by
      variation in introduction pathways and climatic similarity between the native
      range and introduction locality, with minor contributions from phylogeny, species
      ecology, and life history. This finding contrasts with recent evidence that
      particular species characteristics promote evolutionary range expansion and
      reduce the probability of extinction in native populations of amphibians,
      emphasizing how different mechanisms may shape species distributions on different
      temporal and spatial scales. We suggest that contemporary changes in the
      distribution of amphibians will be primarily determined by human-mediated
      extinctions and movement of species within climatic envelopes, and less by
      species-typical traits.

PMID- 22957153
TI  - Parent-offspring conflicts, "optimal bad motherhood" and the "mother knows best"
      principles in insect herbivores colonizing novel host plants.
AB  - SPECIALIZATION OF INSECT HERBIVORES TO ONE OR A FEW HOST PLANTS STIMULATED THE
      DEVELOPMENT OF TWO HYPOTHESES ON HOW NATURAL SELECTION SHOULD SHAPE OVIPOSITION
      PREFERENCES: The "mother knows best" principle suggests that females prefer to
      oviposit on hosts that increase offspring survival. The "optimal bad motherhood"
      principle predicts that females prefer to oviposit on hosts that increase their
      own longevity. In insects colonizing novel host plants, current theory predicts
      that initial preferences of insect herbivores should be maladaptive, leading to
      ecological traps. Ecological trap theory does not take into account the fact that
      insect lineages frequently switch hosts at both ecological and evolutionary time
      scales. Therefore, the behavior of insect herbivores facing novel hosts is also
      shaped by natural selection. Using a study system in which four Cephaloleia
      beetles are currently expanding their diets from native to exotic plants in the
      order Zingiberales, we determined if initial oviposition preferences are
      conservative, maladaptive, or follow the patterns predicted by the "mother knows
      best" or the "optimal bad motherhood" principles. Interactions with novel hosts
      generated parent-offspring conflicts. Larval survival was higher on native hosts.
      However, adult generally lived longer on novel hosts. In Cephaloleia beetles,
      oviposition preferences are usually associated with hosts that increase larval
      survival, female fecundity, and population growth. In most cases, Cephaloleia
      oviposition preferences follow the expectations of the "mothers knows best"
      principle.

PMID- 22957154
TI  - Inferring the annual migration patterns of fall armyworm (Lepidoptera: Noctuidae)
      in the United States from mitochondrial haplotypes.
AB  - Spodoptera frugiperda (J. E. Smith) or fall armyworm is an important agricultural
      pest of a number of crops in the western hemisphere. In the United States,
      infestations in corn acreages extend from the Mexican to the Canadian border.
      Because fall armyworm does not survive prolonged freezing, the infestations
      annually affecting most of North America are migrants from southern Texas and
      Florida, where winter temperatures are mild and host plants are available. A
      haplotype method was developed that can distinguish between these two
      geographically distant overwintering populations, with the potential to delineate
      the associated migratory pathways. Several years of collections from major corn
      producing areas in the southern, central, and eastern United States were used to
      map the geographical distribution of the fall armyworm haplotypes. From these
      haplotype profiles, it was possible to develop the most detailed description yet
      of the annual northward movements of fall armyworm. The consistency of these
      results with past studies and the implications on our understanding of fall
      armyworm biology are discussed. A better understanding of fall armyworm
      populations and their movement is critical for the development of strategies to
      predict infestation levels and eventually control this pest in the United States.

PMID- 22957155
TI  - Hiding deep in the trees: discovery of divergent mitochondrial lineages in
      Malagasy chameleons of the Calumma nasutum group.
AB  - WE CONDUCTED A COMPREHENSIVE MOLECULAR PHYLOGENETIC STUDY FOR A GROUP OF
      CHAMELEONS FROM MADAGASCAR (CHAMAELEONIDAE: Calumma nasutum group, comprising
      seven nominal species) to examine the genetic and species diversity in this
      widespread genus. Based on DNA sequences of the mitochondrial gene (ND2) from 215
      specimens, we reconstructed the phylogeny using a Bayesian approach. Our results
      show deep divergences among several unnamed mitochondrial lineages that are
      difficult to identify morphologically. We evaluated lineage diversification using
      a number of statistical phylogenetic methods (general mixed Yule-coalescent
      model; SpeciesIdentifier; net p-distances) to objectively delimit lineages that
      we here consider as operational taxonomic units (OTUs), and for which the
      taxonomic status remains largely unknown. In addition, we compared molecular and
      morphological differentiation in detail for one particularly diverse clade (the
      C. boettgeri complex) from northern Madagascar. To assess the species boundaries
      within this group we used an integrative taxonomic approach, combining evidence
      from two independent molecular markers (ND2 and CMOS), together with genital and
      other external morphological characters, and conclude that some of the newly
      discovered OTUs are separate species (confirmed candidate species, CCS), while
      others should best be considered as deep conspecific lineages (DCLs). Our
      analysis supports a total of 33 OTUs, of which seven correspond to described
      species, suggesting that the taxonomy of the C. nasutum group is in need of
      revision.

PMID- 22957156
TI  - Assessing the roles of population density and predation risk in the evolution of
      offspring size in populations of a placental fish.
AB  - Population density is an ecological variable that is hypothesized to be a major
      agent of selection on offspring size. In high-density populations, high levels of
      intraspecific competition are expected to favor the production of larger
      offspring. In contrast, lower levels of intraspecific competition and selection
      for large offspring should be weaker and more easily overridden by direct
      selection for increased fecundity in low-density populations. Some studies have
      found associations between population density and offspring size consistent with
      this hypothesis. However, their interpretations are often clouded by a number of
      issues. Here, we use data from a 10-year study of nine populations of the least
      killifish, Heterandria formosa, to describe the associations of offspring size
      with habitat type, population density, and predation risk. We found that females
      from spring populations generally produced larger offspring than females from
      ponds; however, the magnitude of this difference varied among years. Across all
      populations, larger offspring were associated with higher densities and lower
      risks of predation. Interestingly, the associations between the two ecological
      variables (density and predation risk) and offspring size were largely
      independent of one another. Our results suggest that previously described genetic
      differences in offspring size are due to density-dependent natural selection.

PMID- 22957157
TI  - Maintenance of genetic diversity in cyclic populations-a longitudinal analysis in
      Myodes glareolus.
AB  - Conspicuous cyclic changes in population density characterize many populations of
      small northern rodents. The extreme crashes in individual number are expected to
      reduce the amount of genetic variation within a population during the crash
      phases of the population cycle. By long-term monitoring of a bank vole (Myodes
      glareolus) population, we show that despite the substantial and repetitive
      crashes in the population size, high heterozygosity is maintained throughout the
      population cycle. The striking population density fluctuation in fact only
      slightly reduced the allelic richness of the population during the crash phases.
      Effective population sizes of vole populations remained also relatively high even
      during the crash phases. We further evaluated potential mechanisms contributing
      to the genetic diversity of the population and found that the peak phases are
      characterized by both a change in spatial pattern of individuals and a rapid
      accession of new alleles probably due to migration. We propose that these events
      act together in maintaining the high genetic diversity within cyclical
      populations.

PMID- 22957158
TI  - Climatic niche shift predicts thermal trait response in one but not both
      introductions of the Puerto Rican lizard Anolis cristatellus to Miami, Florida,
      USA.
AB  - Global change is predicted to alter environmental conditions for populations in
      numerous ways; for example, invasive species often experience substantial shifts
      in climatic conditions during introduction from their native to non-native
      ranges. Whether these shifts elicit a phenotypic response, and how adaptation and
      phenotypic plasticity contribute to phenotypic change, are key issues for
      understanding biological invasions and how populations may respond to local
      climate change. We combined modeling, field data, and a laboratory experiment to
      test for changing thermal tolerances during the introduction of the tropical
      lizard Anolis cristatellus from Puerto Rico to Miami, Florida. Species
      distribution models and bioclimatic data analyses showed lower minimum
      temperatures, and greater seasonal and annual variation in temperature for Miami
      compared to Puerto Rico. Two separate introductions of A. cristatellus occurred
      in Miami about 12 km apart, one in South Miami and the other on Key Biscayne, an
      offshore island. As predicted from the shift in the thermal climate and the
      thermal tolerances of other Anolis species in Miami, laboratory acclimation and
      field acclimatization showed that the introduced South Miami population of A.
      cristatellus has diverged from its native-range source population by acquiring
      low-temperature acclimation ability. By contrast, the introduced Key Biscayne
      population showed little change compared to its source. Our analyses predicted an
      adaptive response for introduced populations, but our comparisons to native-range
      sources provided evidence for thermal plasticity in one introduced population but
      not the other. The rapid acquisition of thermal plasticity by A. cristatellus in
      South Miami may be advantageous for its long-term persistence there and expansion
      of its non-native range. Our results also suggest that the common assumption of
      no trait variation when modeling non-native species distributions is invalid.

PMID- 22957159
TI  - The endemic gastropod fauna of Lake Titicaca: correlation between molecular
      evolution and hydrographic history.
AB  - Lake Titicaca, situated in the Altiplano high plateau, is the only ancient lake
      in South America. This 2- to 3-My-old (where My is million years) water body has
      had a complex history that included at least five major hydrological phases
      during the Pleistocene. It is generally assumed that these physical events helped
      shape the evolutionary history of the lake's biota. Herein, we study an endemic
      species assemblage in Lake Titicaca, composed of members of the microgastropod
      genus Heleobia, to determine whether the lake has functioned as a reservoir of
      relic species or the site of local diversification, to evaluate congruence of the
      regional paleohydrology and the evolutionary history of this assemblage, and to
      assess whether the geographic distributions of endemic lineages are hierarchical.
      Our phylogenetic analyses indicate that the Titicaca/Altiplano Heleobia fauna
      (together with few extralimital taxa) forms a species flock. A molecular clock
      analysis suggests that the most recent common ancestor (MRCAs) of the Altiplano
      taxa evolved 0.53 (0.28-0.80) My ago and the MRCAs of the Altiplano taxa and
      their extralimital sister group 0.92 (0.46-1.52) My ago. The endemic species of
      Lake Titicaca are younger than the lake itself, implying primarily
      intralacustrine speciation. Moreover, the timing of evolutionary branching events
      and the ages of two precursors of Lake Titicaca, lakes Cabana and Ballivian, is
      congruent. Although Lake Titicaca appears to have been the principal site of
      speciation for the regional Heleobia fauna, the contemporary spatial patterns of
      endemism have been masked by immigration and/or emigration events of local
      riverine taxa, which we attribute to the unstable hydrographic history of the
      Altiplano. Thus, a hierarchical distribution of endemism is not evident, but
      instead there is a single genetic break between two regional clades. We also
      discuss our findings in relation to studies of other regional biota and suggest
      that salinity tolerance was the most likely limiting factor in the evolution of
      Altiplano species flocks.

PMID- 22957160
TI  - A European phylogeography of Rhinanthus minor compared to Rhinanthus
      angustifolius: unexpected splits and signs of hybridization.
AB  - Rhinanthus minor and Rhinanthus angustifolius (Orobanchaceae) are annual
      hemiparasites, which occur sympatrically in Europe and are known to hybridize. We
      studied chloroplast and nuclear (amplified fragment length polymorphism [AFLP])
      diversity in R. minor and compared genetic structuring in this species with R.
      angustifolius by analyzing the AFLP data for both species simultaneously. The
      AFLP data revealed that populations in Italy, Greece, and southeast Russia
      initially identified as R. minor were so distant from the other R. minor
      populations that they probably belong to another, yet unidentified taxon, and we
      refer to them as Rhinanthus sp. R. minor s.s. showed a clear geographic genetic
      structure in both the chloroplast DNA (cpDNA) and nuclear genome. The
      simultaneous analysis of both species shed new light on the previously published
      findings for R. angustifolius, because some populations now turned out to belong
      to R. minor. The admixture analysis revealed very few individuals of mixed R.
      minor-R.angustifolius ancestry in the natural populations in the west of Europe,
      while admixture levels were higher in the east. The combined haplotype network
      showed that haplotype H1 was shared among all species and is likely to be
      ancestral. H2 was more abundant in R. angustifolius and H3 in R. minor, and the
      latter probably arose from H1 in this species in the east of Europe. The
      occurrence of H3 in R. angustifolius may be explained by introgression from R.
      minor, but without interspecific admixture, these are likely to have been old
      hybridization events. Our study underlines the importance of including related
      species in phylogeographic studies.

PMID- 22957161
TI  - Harvest selection on Atlantic cod behavioral traits: implications for spatial
      management.
AB  - Harvesting wild populations may contrast or reinforce natural agents of selection
      and potentially cause evolutionary changes in life-history traits such as growth
      and maturation. Harvest selection may also act on behavioral traits, although
      this field of research has so far received less attention. We used acoustic tags
      and a network of receivers to monitor the behavior and fate of individual
      Atlantic cod (Gadus morhua, N = 60) in their natural habitat on the Norwegian
      Skagerrak coast. Fish with a strong diel vertical migration, alternating between
      shallow- and deep-water habitats, had a higher risk of being captured in the
      fishery (traps, gillnet, hand line) as compared to fish that stayed in deeper
      water. There was also a significant negative correlation between fish size (30-66
      cm) and the magnitude of diel vertical migration. Natural selection on behavior
      was less clear, but tended to favor fish with a large activity space. On a
      monthly time scale we found significant repeatabilities for cod behavior, meaning
      that individual characteristics tended to persist and therefore may be termed
      personality traits. We argue that an evolutionary approach to fisheries
      management should consider fish behavior. This would be of particular relevance
      for spatial management actions such as marine reserve design.

PMID- 22957162
TI  - Long-term breeding phenology shift in royal penguins.
AB  - The Earth's climate is undergoing rapid warming, unprecedented in recent times,
      which is driving shifts in the distribution and phenology of many plants and
      animals. Quantifying changes in breeding phenology is important for understanding
      how populations respond to these changes. While data on shifts in phenology are
      common for Northern Hemisphere species (especially birds), there is a dearth of
      evidence from the Southern Hemisphere, and even fewer data available from the
      marine environment. Surface air temperatures at Macquarie Island have increased
      by 0.62 degrees C during the 30-year study period (0.21 degrees C decade(-1)) and
      royal penguins (Eudyptes schlegeli) commenced egg laying on average three days
      earlier in the 1990s than during the 1960s. This contrasts with other studies of
      Southern Ocean seabirds; five of nine species are now breeding on average 2.1
      days later than during the 1950s. Despite the different direction of these
      trends, they can be explained by a single underlying mechanism: resource
      availability. There was a negative relationship between the Southern Annular Mode
      (SAM) and median laying date of royal penguins, such that low-productivity (low
      SAM) years delayed laying date. This accords with the observations of other
      seabird species from the Antarctic, where later laying dates were associated with
      lower sea ice and lower spring productivity. The unifying factor underpinning
      phenological trends in eastern Antarctica is therefore resource availability; as
      food becomes scarcer, birds breed later. These changes are not uniform across the
      region, however, with resource increases in the subantarctic and decreases in
      eastern Antarctica.

PMID- 22957163
TI  - The evolution of preference strength under sensory bias: a role for indirect
      selection?
AB  - Evidence suggests that female preferences may sometimes arise through sensory
      bias, and that males may subsequently evolve traits that increase their
      conspicuousness to females. Here, we ask whether indirect selection, arising
      through genetic associations (linkage disequilibrium) during the sexual selection
      that sensory bias imposes, can itself influence the evolution of preference
      strength. Specifically, we use population genetic models to consider whether or
      not modifiers of preference strength can spread under different ecological
      conditions when female mate choice is driven by sensory bias. We focus on male
      traits that make a male more conspicuous in certain habitats-and thus both more
      visible to predators and more attractive to females-and examine modifiers of the
      strength of preference for conspicuous males. We first solve for the rate of
      spread of a modifier that strengthens preference within an environmentally
      uniform population; we illustrate that this spread will be extremely slow.
      Second, we used a series of simulations to consider the role of habitat structure
      and movement on the evolution of a modifier of preference strength, using male
      color polymorphisms as a case study. We find that in most cases, indirect
      selection does not allow the evolution of stronger or weaker preferences for
      sensory bias. Only in a "two-island" model, where there is restricted migration
      between different patches that favor different male phenotypes, did we find that
      preference strength could evolve. The role of indirect selection in the evolution
      of sensory bias is of particular interest because of ongoing speculation
      regarding the role of sensory bias in the evolution of reproductive isolation.

PMID- 22957164
TI  - Mitochondrial lineages in Notochthamalus scabrosus as indicators of coastal
      recruitment and interactions.
AB  - A significant genetic cline has previously been identified along the Chilean
      coast in the barnacle Notochthamalus scabrosus. Samples from the previous study,
      spanning 800 km, were not able to show whether the southern lineage ultimately
      goes to fixation at higher latitudes. In addition to expanding the geographic
      sampling of this species, locations that were sampled approximately four to five
      generations ago were resampled for this study, enabling a temporal comparison of
      the location and strength of the observed cline. Here, we show that although the
      cline persists as expected, the tremendous changes in observed lineage
      frequencies near the clinal boundary are indicative of source-sink dynamics that
      may be associated with a codistributed biogeographic transition zone. We also
      find that the southern lineage does not increase in frequency in more southern
      populations, suggesting that this lineage is maintained through a combination of
      density-dependent interactions and a coastal fitness gradient.

PMID- 22957165
TI  - Historic hybridization and introgression between two iconic Australian
      anemonefish and contemporary patterns of population connectivity.
AB  - Endemic species on islands are considered at risk of extinction for several
      reasons, including limited dispersal abilities, small population sizes, and low
      genetic diversity. We used mitochondrial DNA (D-Loop) and 17 microsatellite loci
      to explore the evolutionary relationship between an endemic anemonefish,
      Amphiprion mccullochi (restricted to isolated locations in subtropical eastern
      Australia) and its more widespread sister species, A. akindynos. A mitochondrial
      DNA (mtDNA) phylogram showed reciprocal monophyly was lacking for the two
      species, with two supported groups, each containing representatives of both
      species, but no shared haplotypes and up to 12 species, but not location-specific
      management units (MUs). Population genetic analyses suggested evolutionary
      connectivity among samples of each species (mtDNA), while ecological connectivity
      was only evident among populations of the endemic, A. mccullochi. This suggests
      higher dispersal between endemic anemonefish populations at both evolutionary and
      ecological timeframes, despite separation by hundreds of kilometers. The complex
      mtDNA structure results from historical hybridization and introgression in the
      evolutionary past of these species, validated by msat analyses (NEWHYBRIDS,
      STRUCTURE, and DAPC). Both species had high genetic diversities (mtDNA h > 0.90,
      pi = 4.0%; msat genetic diversity, gd > 0.670). While high gd and connectivity
      reduce extinction risk, identifying and protecting populations implicated in
      generating reticulate structure among these species should be a conservation
      priority.

PMID- 22957166
TI  - Flying with the birds? Recent large-area dispersal of four Australian Limnadopsis
      species (Crustacea: Branchiopoda: Spinicaudata).
AB  - Temporary water bodies are important freshwater habitats in the arid zone of
      Australia. They harbor a distinct fauna and provide important feeding and
      breeding grounds for water birds. This paper assesses, on the basis of haplotype
      networks, analyses of molecular variation and relaxed molecular clock divergence
      time estimates, the phylogeographic history, and population structure of four
      common temporary water species of the Australian endemic clam shrimp taxon
      Limnadopsis in eastern and central Australia (an area of >1,350,000 km(2)).
      Mitochondrial cytochrome c oxidase subunit I sequences of 413 individuals and a
      subset of 63 nuclear internal transcribed spacer 2 sequences were analyzed.
      Genetic differentiation was observed between populations inhabiting southeastern
      and central Australia and those inhabiting the northern Lake Eyre Basin and
      Western Australia. However, over large parts of the study area and across river
      drainage systems in southeastern and central Australia (the Murray-Darling Basin,
      Bulloo River, and southern Lake Eyre Basin), no evidence of population
      subdivision was observed in any of the four Limnadopsis species. This indicates
      recent gene flow across an area of ~800,000 km(2). This finding contrasts with
      patterns observed in other Australian arid zone taxa, particularly freshwater
      species, whose populations are often structured according to drainage systems.
      The lack of genetic differentiation within the area in question may be linked to
      the huge number of highly nomadic water birds that potentially disperse the
      resting eggs of Limnadopsis among temporary water bodies. Genetically
      undifferentiated populations on a large geographic scale contrast starkly with
      findings for many other large branchiopods in other parts of the world, where
      pronounced genetic structure is often observed even in populations inhabiting
      pools separated by a few kilometers. Due to its divergent genetic lineages (up to
      5.6% uncorrected p-distance) and the relaxed molecular clock divergence time
      estimates obtained, Limnadopsis parvispinus is assumed to have inhabited the
      Murray-Darling Basin continuously since the mid-Pliocene (~4 million years ago).
      This means that suitable temporary water bodies would have existed in this area
      throughout the wet-dry cycles of the Pleistocene.

PMID- 22957167
TI  - Diet, sex, and death in field crickets.
AB  - Senescence is shaped by age-dependent trade-offs between fitness components.
      Because males and females invest different resources in reproduction, the trade
      offs behind age-dependent reproductive effort should be resolved differently in
      the sexes. In this study, we assess the effects of diet (high carbohydrate and
      low protein vs. equal carbohydrate and protein) and mating (once mated vs.
      virgin) on lifespan and age-dependent mortality in male and female field crickets
      (Teleogryllus commodus), and on male calling effort. Females always had higher
      actuarial ageing rates than males, and we found a clear lifespan cost of mating
      in females. Mated males, however, lived longer than virgin males, possibly
      because virgins call more than mated males. The fastest age-dependent increases
      in mortality were among mated males on the high-carbohydrate diet. Males on a
      high-carbohydrate diet showed a faster increase in calling effort earlier in
      life, and a more pronounced pattern of senescence once they reached this peak
      than did males on a diet with equal amounts of protein and carbohydrates. Our
      results provide evidence that the cost of mating in this cricket species is both
      diet and sex-dependent, and that the underlying causes of sex differences in life
      history traits such as lifespan and senescence can be complex.

PMID- 22957168
TI  - Interfamily variation in amphibian early life-history traits: raw material for
      natural selection?
AB  - The embryonic development and time to hatching of eggs can be highly adaptive in
      some species, and thus under selective pressure. In this study, we examined the
      underlying interfamily variation in hatching timing and embryonic development in
      a population of an oviparous amphibian, the rough-skinned newt (Taricha
      granulosa). We found significant, high variability in degree of embryonic
      development and hatching timing among eggs from different females. Patterns of
      variation were present regardless of temperature. We also could not explain the
      differences among families by morphological traits of the females or their eggs.
      This study suggests that the variation necessary for natural selection to act
      upon is present in the early life history of this amphibian.

PMID- 22957169
TI  - Evolution of MHC class I genes in the European badger (Meles meles).
AB  - The major histocompatibility complex (MHC) plays a central role in the adaptive
      immune system and provides a good model with which to understand the evolutionary
      processes underlying functional genes. Trans-species polymorphism and orthology
      are both commonly found in MHC genes; however, mammalian MHC class I genes tend
      to cluster by species. Concerted evolution has the potential to homogenize
      different loci, whereas birth-and-death evolution can lead to the loss of
      orthologs; both processes result in monophyletic groups within species. Studies
      investigating the evolution of MHC class I genes have been biased toward a few
      particular taxa and model species. We present the first study of MHC class I
      genes in a species from the superfamily Musteloidea. The European badger (Meles
      meles) exhibits moderate variation in MHC class I sequences when compared to
      other carnivores. We identified seven putatively functional sequences and nine
      pseudogenes from genomic (gDNA) and complementary (cDNA) DNA, signifying at least
      two functional class I loci. We found evidence for separate evolutionary
      histories of the alpha1 and alpha2/alpha3 domains. In the alpha1 domain, several
      sequences from different species were more closely related to each other than to
      sequences from the same species, resembling orthology or trans-species
      polymorphism. Balancing selection and probable recombination maintain genetic
      diversity in the alpha1 domain, evidenced by the detection of positive selection
      and a recombination event. By comparison, two recombination breakpoints indicate
      that the alpha2/alpha3 domains have most likely undergone concerted evolution,
      where recombination has homogenized the alpha2/alpha3 domains between genes,
      leading to species-specific clusters of sequences. Our findings highlight the
      importance of analyzing MHC domains separately.

PMID- 22957170
TI  - Population structure and demographic history of a tropical lowland rainforest
      tree species Shorea parvifolia (Dipterocarpaceae) from Southeastern Asia.
AB  - Distribution of tropical rainforests in Southeastern Asia has changed over geo
      logical time scale, due to movement of tectonic plates and/or global climatic
      changes. Shorea parvifolia is one of the most common tropical lowland rainforest
      tree species in Southeastern Asia. To infer population structure and demographic
      history of S. parvifolia, as indicators of temporal changes in the distribution
      and extent of tropical rainforest in this region, we studied levels and patterns
      of nucleotide polymorphism in the following five nuclear gene regions: GapC,
      GBSSI, PgiC, SBE2, and SODH. Seven populations from peninsular Malaysia, Sumatra,
      and eastern Borneo were included in the analyses. STRUCTURE analysis revealed
      that the investigated populations are divided into two groups: Sumatra-Malay and
      Borneo. Furthermore, each group contained one admixed population. Under isolation
      with migration model, divergence of the two groups was estimated to occur between
      late Pliocene (2.6 MYA) and middle Pleistocene (0.7 MYA). The log-likelihood
      ratio tests of several demographic models strongly supported model with
      population expansion and low level of migration after divergence of the Sumatra
      Malay and Borneo groups. The inferred demographic history of S. parvifolia
      suggested the presence of a scarcely forested land bridge on the Sunda Shelf
      during glacial periods in the Pleistocene and predominance of tropical lowland
      rainforest at least in Sumatra and eastern Borneo.

PMID- 22957171
TI  - "Menage a trois": the presence/absence of thyme shapes the mutualistic
      interaction between the host plant Medicago truncatula (Fabaceae) and its
      symbiotic bacterium Sinorhizobium meliloti.
AB  - The long-term maintenance of specialized mutualisms remains an evolutionary
      puzzle. Recent focus has been on factors governing the stability of these
      mutualisms, including sanctions by the host, partner choice, and coevolutionary
      constraint, that is, the genetic correlation (r(G)) between fitness of both
      partners. So far these studies have been typically carried out in a single
      environment. Here, we ask if the genetic correlation between fitness of the host
      plant Medicago truncatula (Fabaceae) and its bacterial symbiont Sinorhizobium
      meliloti is affected by the presence/absence of a monoterpene (carvacrol) leached
      into the soil by Thymus vulgaris-a common plant of the Mediterranean vegetation,
      often co-occuring with Medicago. We show that the presence of carvacrol in the
      soil dramatically affects fitness of the rhizobial partner and increases the
      magnitude of r(G) between plant and rhizobia fitness (r(G) = 0.02 +/- 0.05 vs.
      r(G) = 0.57 +/- 0.02). This finding emphasizes the importance of heterogeneity in
      the biotic environment for understanding the evolution of species interactions.

PMID- 22957172
TI  - Environmental diel variation, parasite loads, and local population structuring of
      a mixed-mating mangrove fish.
AB  - Genetic variation within populations depends on population size, spatial
      structuring, and environmental variation, but is also influenced by mating
      system. Mangroves are some of the most productive and threatened ecosystems on
      earth and harbor a large proportion of species with mixed-mating (self
      fertilization and outcrossing). Understanding population structuring in mixed
      mating species is critical for conserving and managing these complex ecosystems.
      Kryptolebias marmoratus is a unique mixed-mating vertebrate inhabiting mangrove
      swamps under highly variable tidal regimes and environmental conditions. We
      hypothesized that geographical isolation and ecological pressures influence
      outcrossing rates and genetic diversity, and ultimately determine the local
      population structuring of K. marmoratus. By comparing genetic variation at 32
      microsatellites, diel fluctuations of environmental parameters, and parasite
      loads among four locations with different degrees of isolation, we found
      significant differences in genetic diversity and genotypic composition but little
      evidence of isolation by distance. Locations also differed in environmental diel
      fluctuation and parasite composition. Our results suggest that mating system,
      influenced by environmental instability and parasites, underpins local population
      structuring of K. marmoratus. More generally, we discuss how the conservation of
      selfing species inhabiting mangroves and other biodiversity hotspots may benefit
      from knowledge of mating strategies and population structuring at small spatial
      scales.

PMID- 22957173
TI  - Complex agro-ecosystems for food security in a changing climate.
AB  - Attempts to increase food crop yields by intensifying agricultural systems using
      high inputs of nonrenewable resources and chemicals frequently lead to de
      gradation of natural resources, whereas most technological innovations are not
      accessible for smallholders that represent the majority of farmers world wide.
      Alternatively, cocultures consisting of assemblages of plant and animal species
      can support ecological processes of nutrient cycling and pest control, which may
      lead to increasing yields and declining susceptibility to extreme weather
      conditions with increasing complexity of the systems. Here we show that enhancing
      the complexity of a rice production system by adding combinations of compost,
      azolla, ducks, and fish resulted in strongly increased grain yields and revenues
      in a season with extremely adverse weather conditions on East Java, Indonesia. We
      found that azolla, duck, and fish increased plant nutrient content, tillering and
      leaf area expansion, and strongly reduced the density of six different pests. In
      the most complex system comprising all components the highest grain yield was
      obtained. The net revenues of this system from sales of rice grain, fish, and
      ducks, after correction for extra costs, were 114% higher than rice cultivation
      with only compost as fertilizer. These results provide more insight in the agro
      ecological processes and demonstrate how complex agricultural systems can
      contribute to food security in a changing climate. If smallholders can be trained
      to manage these systems and are supported for initial investments by credits,
      their livelihoods can be improved while producing in an ecologically benign way.

PMID- 22957174
TI  - The evolution of disease resistance and tolerance in spatially structured
      populations.
AB  - THE UBIQUITOUS CHALLENGE FROM INFECTIOUS DISEASE HAS PROMPTED THE EVOLUTION OF
      DIVERSE HOST DEFENSES, WHICH CAN BE DIVIDED INTO TWO BROAD CLASSES: resistance
      (which limits pathogen growth and infection) and tolerance (which does not limit
      infection, but instead reduces or offsets its negative fitness consequences).
      Resistance and tolerance may provide equivalent short-term benefits, but have
      fundamentally different epidemiological consequences and thus exhibit different
      evolutionary behaviors. We consider the evolution of resistance and tolerance in
      a spatially structured population using a stochastic simulation model. We show
      that tolerance can invade a population of susceptible individuals (i.e., neither
      resistant nor tolerant) with higher cost than resistance, even though they each
      provide equivalent direct benefits to the host, because tolerant hosts impose
      higher disease burden upon vulnerable competitors. However, in spatially
      structured settings, tolerance can invade a population of resistant hosts only
      with lower cost than resistance due to spatial genetic structure and the higher
      local incidence of disease around invading tolerant individuals. The evolution of
      tolerance is therefore constrained by spatial genetic structure in a manner not
      previously revealed by nonspatially explicit models, suggesting mechanisms that
      could maintain variation or limit the occurrence of tolerance relative to
      resistance.

PMID- 22957175
TI  - Impacts of upstream drought and water withdrawals on the health and survival of
      downstream estuarine oyster populations.
AB  - Increases in the frequency, duration, and severity of regional drought pose major
      threats to the health and integrity of downstream ecosystems. During 2007-2008,
      the U.S. southeast experienced one of the most severe droughts on record. Drought
      and water withdrawals in the upstream watershed led to decreased freshwater input
      to Apalachicola Bay, Florida, an estuary that is home to a diversity of
      commercially and ecologically important organisms. This study applied a
      combination of laboratory experiments and field observations to investigate the
      effects of reduced freshwater input on Apalachicola oysters. Oysters suffered
      significant disease-related mortality under high-salinity, drought conditions,
      particularly during the warm summer months. Mortality was size-specific, with
      large oysters of commercially harvestable size being more susceptible than small
      oysters. A potential salinity threshold was revealed between 17 and 25 ppt, where
      small oysters began to suffer mortality, and large oysters exhibited an increase
      in mortality. These findings have important implications for watershed
      management, because upstream freshwater releases could be carefully timed and
      allocated during stressful periods of the summer to reduce disease-related oyster
      mortality. Integrated, forward-looking water management is needed, particularly
      under future scenarios of climate change and human population growth, to sustain
      the valuable ecosystem services on which humans depend.

PMID- 22957176
TI  - Longitudinal differentiation among pelagic populations in a planktic foraminifer.
AB  - Evolutionary processes in marine plankton have been assumed to be dependent on
      the oceanic circulation system, which transports plankton between populations in
      marine surface waters. Gene flow facilitated by oceanic currents along
      longitudinal gradients may efficiently impede genetic differentiation of pelagic
      populations in the absence of confounding marine environmental effects. However,
      how responsible oceanic currents are for the geographic distribution and
      dispersal of plankton is poorly understood. We examined the phylogeography of the
      planktic foraminifer Pulleniatina obliquiloculata in the Indo-Pacific Warm Pool
      (IPWP) by using partial small subunit ribosomal DNA (SSU rDNA) sequences. We
      found longitudinal clines in the frequencies of three distinct genetic types in
      the IPWP area. These frequencies were correlated with environmental factors that
      are characteristic of three water masses in the IPWP. Noteworthy, populations
      inhabiting longitudinally distant water masses at the Pacific and Indian sides of
      the IPWP were genetically different, despite transportation of individuals via
      oceanic currents. These results demonstrate that populations of pelagic plankton
      have diverged genetically among different water masses within a single climate
      zone. Changes of the oceanic circulation system could have impacted the
      geographic patterns of dispersal and divergence of pelagic plankton.

PMID- 22957177
TI  - Ontogeny and sex alter the effect of predation on body shape in a livebearing
      fish: sexual dimorphism, parallelism, and costs of reproduction.
AB  - Predation can cause morphological divergence among populations, while ontogeny
      and sex often determine much of morphological diversity among individuals. We
      used geometric morphometrics to characterize body shape in the livebearing fish
      Brachyrhaphis rhabdophora to test for interactions between these three major
      shape-determining factors. We assessed shape variation between juveniles and
      adults of both sexes, and among adults for populations from high- and low
      predation areas. Shape differed significantly between predation regimes for all
      juveniles regardless of sex. As males grew and matured into adults, ontogenetic
      shape trajectories were parallel, thus maintaining shape differences in adult
      males between predation environments. However, shape of adult females between
      predation environments followed a different pattern. As females grew and matured,
      ontogenetic shape trajectories converged so that shape differences were less
      pronounced between mature females in predator and nonpredator environments.
      Convergence in female body shape may indicate a trade-off between optimal shape
      for predator evasion versus shape required for the livebearing mode of
      reproduction.

PMID- 22957178
TI  - Consequences of high temperatures and premature mortality on the transcriptome
      and blood physiology of wild adult sockeye salmon (Oncorhynchus nerka).
AB  - Elevated river water temperature in the Fraser River, British Columbia, Canada,
      has been associated with enhanced mortality of adult sockeye salmon (Oncorhynchus
      nerka) during their upriver migration to spawning grounds. We undertook a study
      to assess the effects of elevated water temperatures on the gill transcriptome
      and blood plasma variables in wild-caught sockeye salmon. Naturally migrating
      sockeye salmon returning to the Fraser River were collected and held at
      ecologically relevant temperatures of 14 degrees C and 19 degrees C for seven
      days, a period representing a significant portion of their upstream migration.
      After seven days, sockeye salmon held at 19 degrees C stimulated heat shock
      response genes as well as many genes associated with an immune response when
      compared with fish held at 14 degrees C. Additionally, fish at 19 degrees C had
      elevated plasma chloride and lactate, suggestive of a disturbance in
      osmoregulatory homeostasis and a stress response detectable in the blood plasma.
      Fish that died prematurely over the course of the holding study were compared
      with time-matched surviving fish; the former fish were characterized by an
      upregulation of several transcription factors associated with apoptosis and
      downregulation of genes involved in immune function and antioxidant activity.
      Ornithine decarboxylase (ODC1) was the most significantly upregulated gene in
      dying salmon, which suggests an association with cellular apoptosis. We
      hypothesize that the observed decrease in plasma ions and increases in plasma
      cortisol that occur in dying fish may be linked to the increase in ODC1. By
      highlighting these underlying physiological mechanisms, this study enhances our
      understanding of the processes involved in premature mortality and temperature
      stress in Pacific salmon during migration to spawning grounds.

PMID- 22957179
TI  - A maximum likelihood approach to generate hypotheses on the evolution and
      historical biogeography in the Lower Volga Valley regions (southwest Russia).
AB  - The evolution of the diverse flora in the Lower Volga Valley (LVV) (southwest
      Russia) is complex due to the composite geomorphology and tectonic history of the
      Caspian Sea and adjacent areas. In the absence of phylogenetic studies and
      temporal information, we implemented a maximum likelihood (ML) approach and
      stochastic character mapping reconstruction aiming at recovering historical
      signals from species occurrence data. A taxon-area matrix of 13 floristic areas
      and 1018 extant species was constructed and analyzed with RAxML and Mesquite.
      Additionally, we simulated scenarios with numbers of hypothetical extinct taxa
      from an unknown palaeoflora that occupied the areas before the dramatic
      transgression and regression events that have occurred from the Pleistocene to
      the present day. The flora occurring strictly along the river valley and delta
      appear to be younger than that of adjacent steppes and desert-like regions,
      regardless of the chronology of transgression and regression events that led to
      the geomorphological formation of the LVV. This result is also supported when
      hypothetical extinct taxa are included in the analyses. The history of each
      species was inferred by using a stochastic character mapping reconstruction
      method as implemented in Mesquite. Individual histories appear to be independent
      from one another and have been shaped by repeated dispersal and extinction
      events. These reconstructions provide testable hypotheses for more in-depth
      investigations of their population structure and dynamics.

PMID- 22957181
TI  - A complex speciation-richness relationship in a simple neutral model.
AB  - Speciation is the "elephant in the room" of community ecology. As the ultimate
      source of biodiversity, its integration in ecology's theoretical corpus is
      necessary to understand community assembly. Yet, speciation is often completely
      ignored or stripped of its spatial dimension. Recent approaches based on network
      theory have allowed ecologists to effectively model complex landscapes. In this
      study, we use this framework to model allopatric and parapatric speciation in
      networks of communities. We focus on the relationship between speciation,
      richness, and the spatial structure of communities. We find a strong opposition
      between speciation and local richness, with speciation being more common in
      isolated communities and local richness being higher in more connected
      communities. Unlike previous models, we also find a transition to a positive
      relationship between speciation and local richness when dispersal is low and the
      number of communities is small. We use several measures of centrality to
      characterize the effect of network structure on diversity. The degree, the
      simplest measure of centrality, is the best predictor of local richness and
      speciation, although it loses some of its predictive power as connectivity grows.
      Our framework shows how a simple neutral model can be combined with network
      theory to reveal complex relationships between speciation, richness, and the
      spatial organization of populations.

PMID- 22957182
TI  - Inbreeding rate modifies the dynamics of genetic load in small populations.
AB  - The negative fitness consequences of close inbreeding are widely recognized, but
      predicting the long-term effects of inbreeding and genetic drift due to limited
      population size is not straightforward. As the frequency and homozygosity of
      recessive deleterious alleles increase, selection can remove (purge) them from a
      population, reducing the genetic load. At the same time, small population size
      relaxes selection against mildly harmful mutations, which may lead to
      accumulation of genetic load. The efficiency of purging and the accumulation of
      mutations both depend on the rate of inbreeding (i.e., population size) and on
      the nature of mutations. We studied how increasing levels of inbreeding affect
      offspring production and extinction in experimental Drosophila littoralis
      populations replicated in two sizes, N = 10 and N = 40. Offspring production and
      extinction were measured over 25 generations concurrently with a large control
      population. In the N = 10 populations, offspring production decreased strongly at
      low levels of inbreeding, then recovered only to show a consistent subsequent
      decline, suggesting early expression and purging of recessive highly deleterious
      alleles and subsequent accumulation of mildly harmful mutations. In the N = 40
      populations, offspring production declined only after inbreeding reached higher
      levels, suggesting that inbreeding and genetic drift pose a smaller threat to
      population fitness when inbreeding is slow. Our results suggest that highly
      deleterious alleles can be purged in small populations already at low levels of
      inbreeding, but that purging does not protect the small populations from eventual
      genetic deterioration and extinction.

PMID- 22957183
TI  - Waterfalls drive parallel evolution in a freshwater goby.
AB  - Waterfalls may affect fish distribution and genetic structure within drainage
      networks even to the extent of leading evolutionary events. Here, parallel
      evolution was studied by focusing on waterfall and the landlocked freshwater goby
      Rhinogobius sp. YB (YB), which evolved from amphidromous R. brunneus (BR). The
      fish fauna was surveyed at 30 sites in 11 rivers on Iriomote Island, Japan, the
      geography of which was characterized by terraces/tablelands with many waterfalls.
      We found that all YB individuals were distributed only above waterfalls (height
      6.8-58.7 m), whereas BR, and other fishes, were mostly distributed below
      waterfalls. Mitochondrial DNA analysis showed that every YB local population
      above the waterfall was independently evolved from BR. In contrast, cluster
      analysis of nine morphological characters, such as fin color and body pattern,
      showed that the morphology of YB individuals held a similarity beyond the genetic
      divergence, suggesting parallel evolution has occurred relating to their
      morphology. Genetic distance between each YB local population and BR was
      significantly correlated with waterfall height (r(2) = 0.94), suggesting that the
      waterfalls have been heightened due to the constant geological erosion and that
      their height represents the isolation period of YB local populations from BR (ca.
      11,000-88,000 years). Each local population of BR was once landlocked in upstream
      by waterfall formation, consequently evolving to YB in each site. Although the
      morphology of YB had a high degree of similarity among local populations, finer
      scale analysis showed that the morphology of YB was significantly correlated with
      the genetic distance from BR. Consequently, there could be simultaneous multiple
      phases of allopatric/parallel evolution of the goby due to variations in
      waterfall height on this small island.

PMID- 22957184
TI  - Shifts in species richness, herbivore specialization, and plant resistance along
      elevation gradients.
AB  - Environmental gradients have been postulated to generate patterns of diversity
      and diet specialization, in which more stable environments, such as tropical
      regions, should promote higher diversity and specialization. Using field sampling
      and phylogenetic analyses of butterfly fauna over an entire alpine region, we
      show that butterfly specialization (measured as the mean phylogenetic distance
      between utilized host plants) decreases at higher elevations, alongside a
      decreasing gradient of plant diversity. Consistent with current hypotheses on the
      relationship between biodiversity and the strength of species interactions, we
      experimentally show that a higher level of generalization at high elevations is
      associated with lower levels of plant resistance: across 16 pairs of plant
      species, low-elevation plants were more resistant vis-a-vis their congeneric
      alpine relatives. Thus, the links between diversity, herbivore diet
      specialization, and plant resistance along an elevation gradient suggest a causal
      relationship analogous to that hypothesized along latitudinal gradients.

PMID- 22957185
TI  - Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?
AB  - Filoviruses have to date been considered as consisting of one diverse genus
      (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider
      this idea by means of detailed phylogenetic analyses of sequence data available
      for the Filoviridae: using coalescent simulations, we ascertain that two Marburg
      isolates (termed the "RAVN" strain) represent a quite-distinct lineage that
      should be considered in studies of biogeography and host associations, and may
      merit recognition at the level of species. In contrast, filovirus isolates
      recently obtained from bat tissues are not distinct from previously known
      strains, and should be considered as drawn from the same population. Implications
      for understanding the transmission geography and host associations of these
      viruses are discussed.

PMID- 22957186
TI  - How much can the orientation of G's eigenvectors tell us about genetic
      constraints?
AB  - A key goal in evolutionary quantitative genetics is to understand how
      evolutionary trajectories are constrained by pleiotropic coupling among multiple
      traits. Because studying pleiotropic constraints directly at the molecular
      genetic level remains very difficult, several analytical approaches attempt to
      draw conclusions about constraints by relating the orientation of the
      eigenvectors of the traits' (co)variance matrix to vectors of multivariate
      selection. On the basis of explicit models of genetic architecture, I here argue
      that the value of such approaches is greatly overestimated. The reason is that
      eigenvector orientation can be highly unstable and lack a biologically meaningful
      relationship with the underlying traits' genetic architecture. Genetic
      constraints are more profitably explored through experimental approaches avoiding
      the mathematical abstraction inherent in eigenanalysis.

PMID- 22957187
TI  - Evidence of a strong coupling between root exudation, C and N availability, and
      stimulated SOM decomposition caused by rhizosphere priming effects.
AB  - Increased temperatures and concomitant changes in vegetation patterns are
      expected to dramatically alter the functioning of northern ecosystems over the
      next few decades. Predicting the ecosystem response to such a shift in climate
      and vegetation is complicated by the lack of knowledge about the links between
      aboveground biota and belowground process rates. Current models suggest that
      increasing temperatures and rising concentrations of atmospheric CO(2) will be
      partly mitigated by elevated C sequestration in plant biomass and soil. However,
      empirical evidence does not always support this assumption, as elevated
      temperature and CO(2) concentrations also accelerate the belowground C flux, in
      many cases extending to increased decomposition of soil organic matter (SOM) and
      ultimately resulting in decreased soil C stocks. The mechanism behind the
      increase has remained largely unknown, but it has been suggested that priming
      might be the causative agent. Here, we provide quantitative evidence of a strong
      coupling between root exudation, SOM decomposition, and release of plant
      available N caused by rhizosphere priming effects. As plants tend to increase
      belowground C allocation with increased temperatures and CO(2) concentrations,
      priming effects need to be considered in our long-term analysis of soil C budgets
      in a changing environment. The extent of priming seems to be intimately linked to
      resource availability, as shifts in the stoichiometric nutrient demands of plants
      and microorganisms will lead to either cooperation (resulting in priming) or
      competition (no priming will occur). The findings lead us on the way to resolve
      the varying response of primary production, SOM decomposition, and release of
      plant available N to elevated temperatures, CO(2) concentrations, and N
      availability.

PMID- 22957188
TI  - Large-scale asymmetric introgression of cytoplasmic DNA reveals Holocene range
      displacement in a North American boreal pine complex.
AB  - Jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta var. latifolia)
      are two North American boreal hard pines that hybridize in their zone of contact
      in western Canada. The main objective of this study was to characterize their
      patterns of introgression resulting from past and recent gene flow, using
      cytoplasmic markers having maternal or paternal inheritance. Mitochondrial DNA
      (mtDNA) and chloroplast DNA (cpDNA) diversity was assessed in allopatric
      populations of each species and in stands from the current zone of contact
      containing morphological hybrids. Cluster analyses were used to identify genetic
      discontinuities among groups of populations. A canonical analysis was also
      conducted to detect putative associations among cytoplasmic DNA variation, tree
      morphology, and site ecological features. MtDNA introgression was extensive and
      asymmetric: it was detected in P. banksiana populations from the hybrid zone and
      from allopatric areas, but not in P. contorta populations. Very weak cpDNA
      introgression was observed, and only in P. banksiana populations. The mtDNA
      introgression pattern indicated that central Canada was first colonized by
      migrants from a P. contorta glacial population located west of the Rocky
      Mountains, before being replaced by P. banksiana migrating westward during the
      Holocene. In contrast, extensive pollen gene flow would have erased the cpDNA
      traces of this ancient presence of P. contorta. Additional evidence for this
      process was provided by the results of canonical analysis, which indicated that
      the current cpDNA background of trees reflected recent pollen gene flow from the
      surrounding dominant species rather than historical events that took place during
      the postglacial colonization.

PMID- 22957189
TI  - Rarity and genetic diversity in Indo-Pacific Acropora corals.
AB  - Among various potential consequences of rarity is genetic erosion. Neutral
      genetic theory predicts that rare species will have lower genetic diversity than
      common species. To examine the association between genetic diversity and rarity,
      variation at eight DNA microsatellite markers was documented for 14 Acropora
      species that display different patterns of distribution and abundance in the Indo
      Pacific Ocean. Our results show that the relationship between rarity and genetic
      diversity is not a positive linear association because, contrary to expectations,
      some rare species are genetically diverse and some populations of common species
      are genetically depleted. Our data suggest that inbreeding is the most likely
      mechanism of genetic depletion in both rare and common corals, and that
      hybridization is the most likely explanation for higher than expected levels of
      genetic diversity in rare species. A significant hypothesis generated from our
      study with direct conservation implications is that as a group, Acropora corals
      have lower genetic diversity at neutral microsatellite loci than may be expected
      from their taxonomic diversity, and this may suggest a heightened susceptibility
      to environmental change. This hypothesis requires validation based on genetic
      diversity estimates derived from a large portion of the genome.

PMID- 22957191
TI  - Atypical reproductive cycles in a population of Sceloporus grammicus (Squamata:
      Phrynosomatidae) from the Mexican Plateau.
AB  - The spiny lizard Sceloporus grammicus (Squamata: Phrynosomatidae) is a small
      reptile from central Mexico and the southern United States, occurring in a wide
      geographic area characterized by extensive variation in topographic and climatic
      regimes. Genetic variation among lineages from central Mexico is substantial,
      though the extent to which this variation corresponds with life-history traits
      remains obscure. To address part of this puzzle, we studied a population of S.
      grammicus from Tepeapulco, Hidalgo, Mexico. Male-biased sexual dimorphism was
      extensive in this population; males were larger than females overall, and
      expressed proportionately larger heads and longer limbs. Minimum size at sexual
      maturity was similar in the sexes (males: 43 mm; females: 42 mm). In contrast to
      other populations from the Central Plateau, reproductive activity of males and
      females was synchronous. Testicular recrudescence of adult males was initiated in
      October-November, and maximum testis size maintained from December to July.
      Female reproductive activity showed no clear seasonal pattern: females had
      vitellogenic follicles from October to July, and pregnant females were found
      throughout the year. Female body size was not related to litter size. Neither
      male nor female gonadal mass was correlated with any abiotic environmental
      variable examined. Differences in reproductive characteristics among populations
      of S. grammicus might be indicative of plasticity in response to local
      environmental conditions, local adaptation, or complex gene * environment
      interactions. We consider these results in the context of previously studied
      populations of S. grammicus from the Central Plateau and elsewhere, and propose
      directions for future research.

PMID- 22957190
TI  - Hybridization and population structure of the Culex pipiens complex in the
      islands of Macaronesia.
AB  - The Culex pipiens complex includes two widespread mosquito vector species, Cx.
      pipiens and Cx. quinquefasciatus. The distribution of these species varies in
      latitude, with the former being present in temperate regions and the latter in
      tropical and subtropical regions. However, their distribution range overlaps in
      certain areas and interspecific hybridization has been documented. Genetic
      introgression between these species may have epidemiological repercussions for
      West Nile virus (WNV) transmission. Bayesian clustering analysis based on
      multilocus genotypes of 12 microsatellites was used to determine levels of
      hybridization between these two species in Macaronesian islands, the only contact
      zone described in West Africa. The distribution of the two species reflects both
      the islands' biogeography and historical aspects of human colonization. Madeira
      Island displayed a homogenous population of Cx. pipiens, whereas Cape Verde
      showed a more intriguing scenario with extensive hybridization. In the islands of
      Brava and Santiago, only Cx. quinquefasciatus was found, while in Fogo and Maio
      high hybrid rates (~40%) between the two species were detected. Within the
      admixed populations, second-generation hybrids (~50%) were identified suggesting
      a lack of isolation mechanisms. The observed levels of hybridization may locally
      potentiate the transmission to humans of zoonotic arboviruses such as WNV.

PMID- 22957192
TI  - Limited condition dependence of male acoustic signals in the grasshopper
      Chorthippus biguttulus.
AB  - In many animal species, male acoustic signals serve to attract a mate and
      therefore often play a major role for male mating success. Male body condition is
      likely to be correlated with male acoustic signal traits, which signal male
      quality and provide choosy females indirect benefits. Environmental factors such
      as food quantity or quality can influence male body condition and therefore
      possibly lead to condition-dependent changes in the attractiveness of acoustic
      signals. Here, we test whether stressing food plants influences acoustic signal
      traits of males via condition-dependent expression of these traits. We examined
      four male song characteristics, which are vital for mate choice in females of the
      grasshopper Chorthippus biguttulus. Only one of the examined acoustic traits,
      loudness, was significantly altered by changing body condition because of drought
      and moisture-related stress of food plants. No condition dependence could be
      observed for syllable to pause ratio, gap duration within syllables, and onset
      accentuation. We suggest that food plant stress and therefore food plant quality
      led to shifts in loudness of male grasshopper songs via body condition changes.
      The other three examined acoustic traits of males do not reflect male body
      condition induced by food plant quality.

PMID- 22957193
TI  - Strength of density feedback in census data increases from slow to fast life
      histories.
AB  - Life-history theory predicts an increasing rate of population growth among
      species arranged along a continuum from slow to fast life histories. We examine
      the effects of this continuum on density-feedback strength estimated using long
      term census data from >700 vertebrates, invertebrates, and plants. Four life
      history traits (Age at first reproduction, Body size, Fertility, Longevity) were
      related statistically to Gompertz strength of density feedback using generalized
      linear mixed-effects models and multi-model inference. Life-history traits alone
      explained 10 to 30% of the variation in strength across species (after
      controlling for time-series length and phylogenetic nonindependence). Effect
      sizes were largest for body size in mammals and longevity in birds, and density
      feedback was consistently stronger for smaller-bodied and shorter-lived species.
      Overcompensatory density feedback (strength <-1) occurred in 20% of species,
      predominantly at the fast end of the life-history continuum, implying relatively
      high population variability. These results support the idea that life history
      leaves an evolutionary signal in long-term population trends as inferred from
      census data. Where there is a lack of detailed demographic data, broad life
      history information can inform management and conservation decisions about
      rebound capacity from low numbers, and propensity to fluctuate, of arrays of
      species in areas planned for development, harvesting, protection, and population
      recovery.

PMID- 22957194
TI  - Fungal soil communities in a young transgenic poplar plantation form a rich
      reservoir for fungal root communities.
AB  - Fungal communities play a key role in ecosystem functioning. However, only little
      is known about their composition in plant roots and the soil of biomass
      plantations. The goal of this study was to analyze fungal biodiversity in their
      belowground habitats and to gain information on the strategies by which
      ectomycorrhizal (ECM) fungi form colonies. In a 2-year-old plantation, fungal
      communities in the soil and roots of three different poplar genotypes (Populus *
      canescens, wildtype and two transgenic lines with suppressed cinnamyl alcohol
      dehydrogenase activity) were analyzed by 454 pyrosequencing targeting the rDNA
      internal transcribed spacer 1 (ITS) region. The results were compared with the
      dynamics of the root-associated ECM community studied by morphotyping/Sanger
      sequencing in two subsequent years. Fungal species and family richness in the
      soil were surprisingly high in this simple plantation ecosystem, with 5944
      operational taxonomic units (OTUs) and 186 described fungal families. These
      findings indicate the importance that fungal species are already available for
      colonization of plant roots (2399 OTUs and 115 families). The transgenic
      modification of poplar plants had no influence on fungal root or soil
      communities. Fungal families and OTUs were more evenly distributed in the soil
      than in roots, probably as a result of soil plowing before the establishment of
      the plantation. Saprophytic, pathogenic, and endophytic fungi were the dominating
      groups in soil, whereas ECMs were dominant in roots (87%). Arbuscular mycorrhizal
      diversity was higher in soil than in roots. Species richness of the root
      associated ECM community, which was low compared with ECM fungi detected by 454
      analyses, increased after 1 year. This increase was mainly caused by ECM fungal
      species already traced in the preceding year in roots. This result supports the
      priority concept that ECMs present on roots have a competitive advantage over
      soil-localized ECM fungi.

PMID- 22957195
TI  - From where did the Western honeybee (Apis mellifera) originate?
AB  - The native range of the honeybee Apis mellifera encompasses Europe, Africa, and
      the Middle East, whereas the nine other species of Apis are found exclusively in
      Asia. It is therefore commonly assumed that A. mellifera arose in Asia and
      expanded into Europe and Africa. However, other hypotheses for the origin of A.
      mellifera have also been proposed based on phylogenetic trees constructed from
      genetic markers. In particular, an analysis based on >1000 single-nucleotide
      polymorphism markers placed the root of the tree of A. mellifera subspecies among
      samples from Africa, suggestive of an out-of-Africa expansion. Here, we re
      evaluate the evidence for this and other hypotheses by testing the robustness of
      the tree topology to different tree-building methods and by removing specimens
      with a potentially hybrid background. These analyses do not unequivocally place
      the root of the tree of A. mellifera subspecies within Africa, and are
      potentially consistent with a variety of hypotheses for honeybee evolution,
      including an expansion out of Asia. Our analyses also support high divergence
      between western and eastern European populations of A. mellifera, suggesting they
      are likely derived from two distinct colonization routes, although the sources of
      these expansions are still unclear.

PMID- 22957196
TI  - Adaptive radiation in extremophilic Dorvilleidae (Annelida): diversification of a
      single colonizer or multiple independent lineages?
AB  - Metazoan inhabitants of extreme environments typically evolved from forms found
      in less extreme habitats. Understanding the prevalence with which animals move
      into and ultimately thrive in extreme environments is critical to elucidating how
      complex life adapts to extreme conditions. Methane seep sediments along the
      Oregon and California margins have low oxygen and very high hydrogen sulfide
      levels, rendering them inhospitable to many life forms. Nonetheless, several
      closely related lineages of dorvilleid annelids, including members of
      Ophryotrocha, Parougia, and Exallopus, thrive at these sites in association with
      bacterial mats and vesicomyid clam beds. These organisms are ideal for examining
      adaptive radiations in extreme environments. Did dorvilleid annelids invade these
      extreme environments once and then diversify? Alternatively, did multiple
      independent lineages adapt to seep conditions? To address these questions, we
      examined the evolutionary history of methane-seep dorvilleids using 16S and Cyt b
      genes in an ecological context. Our results indicate that dorvilleids invaded
      these extreme habitats at least four times, implying preadaptation to life at
      seeps. Additionally, we recovered considerably more dorvilleid diversity than is
      currently recognized. A total of 3 major clades (designated "Ophryotrocha,"
      "Mixed Genera" and "Parougia") and 12 terminal lineages or species were
      encountered. Two of these lineages represented a known species, Parougia
      oregonensis, whereas the remaining 10 lineages were newly discovered species.
      Certain lineages exhibited affinity to geography, habitat, sediment depth, and/or
      diet, suggesting that dorvilleids at methane seeps radiated via specialization
      and resource partitioning.

PMID- 22957197
TI  - Variation in predator species abundance can cause variable selection pressure on
      warning signaling prey.
AB  - Predation pressure is expected to drive visual warning signals to evolve toward
      conspicuousness. However, coloration of defended species varies tremendously and
      can at certain instances be considered as more camouflaged rather than
      conspicuous. Recent theoretical studies suggest that the variation in signal
      conspicuousness can be caused by variation (within or between species) in
      predators' willingness to attack defended prey or by the broadness of the
      predators' signal generalization. If some of the predator species are capable of
      coping with the secondary defenses of their prey, selection can favor reduced
      prey signal conspicuousness via reduced detectability or recognition. In this
      study, we combine data collected during three large-scale field experiments to
      assess whether variation in avian predator species (red kite, black kite, common
      buzzard, short-toed eagle, and booted eagle) affects the predation pressure on
      warningly and non-warningly colored artificial snakes. Predation pressure varied
      among locations and interestingly, if common buzzards were abundant, there were
      disadvantages to snakes possessing warning signaling. Our results indicate that
      predator community can have important consequences on the evolution of warning
      signals. Predators that ignore the warning signal and defense can be the key for
      the maintenance of variation in warning signal architecture and maintenance of
      inconspicuous signaling.

PMID- 22957198
TI  - Song convergence in multiple urban populations of silvereyes (Zosterops
      lateralis).
AB  - Recent studies have revealed differences between urban and rural vocalizations of
      numerous bird species. These differences include frequency shifts, amplitude
      shifts, altered song speed, and selective meme use. If particular memes sung by
      urban populations are adapted to the urban soundscape, "urban-typical" calls,
      memes, or repertoires should be consistently used in multiple urban populations
      of the same species, regardless of geographic location. We tested whether songs
      or contact calls of silvereyes (Zosterops lateralis) might be subject to such
      convergent cultural evolution by comparing syllable repertoires of geographically
      dispersed urban and rural population pairs throughout southeastern Australia.
      Despite frequency and tempo differences between urban and rural calls, call
      repertoires were similar between habitat types. However, certain song syllables
      were used more frequently by birds from urban than rural populations. Partial
      redundancy analysis revealed that both geographic location and habitat
      characteristics were important predictors of syllable repertoire composition.
      These findings suggest convergent cultural evolution: urban populations modify
      both song and call syllables from their local repertoire in response to noise.

PMID- 22957199
TI  - The effect of nutrient enrichment on the growth, nucleic acid concentrations, and
      elemental stoichiometry of coral reef macroalgae.
AB  - The growth rate hypothesis (GRH) links growth rates with organism elemental
      stoichiometry. Support for the GRH was found for many animal species, but less so
      for plants. This is the first study to test the GRH in macroalgae. Tropical coral
      reef macroalgae from three lineages, Caulerpa serrulata (Chlorophyta), Laurencia
      intricata (Rhodophyta), and Sargassum polyphyllum (Phaeophyceae) were grown
      enriched with nitrogen or phosphorous and under control conditions at Heron
      Island on the Great Barrier Reef, Australia. Growth rate, photosynthesis, nucleic
      acid composition, and elemental stoichiometry were measured. Nutrient enrichment
      had positive effects on photosynthetic rates and on investment in RNA. However,
      growth rate was not correlated with either photosynthetic rates or RNA content;
      thus, we did not find support for the GRH in tropical macroalgae. Macroalgae,
      especially L. intricata, accumulated P to very high levels (>0.6% of dry weight).
      The growth rate response to tissue P concentrations was unimodal. Above 0.21%, P
      accumulation had negative effects on growth. Nitrogen was not stored, but
      evidence of futile cycling was observed. The capacity to store large amounts of P
      is probably an adaptation to the low and patchy nutrient environment of the
      tropical oceans.

PMID- 22957200
TI  - Genome-wide and molecular evolution analysis of the Poplar KT/HAK/KUP potassium
      transporter gene family.
AB  - As the largest K(+) transport gene family, KT/HAK/KUP family plays an important
      role in plant growth, development, and stress adaptation. However, there is
      limited information about this family in woody plant species. In this study, with
      genome-wide in-depth investigation, 31 Poplar KT/HAK/KUP transporter genes
      including six pairs of tandem duplicated and eight pairs of segmental duplicated
      paralogs have been identified, suggesting segmental and tandem duplication events
      contributed to the expansion of this family in Poplar. The combination of
      phylogenetic, exon structure and splice site, and paragon analysis revealed 11
      pairs of Poplar KT/HAK/KUP duplicates. For these 11 pairs, all pairs are subject
      to purify selection, and asymmetric evolutionary rates have been found to occur
      in three pairs. This study might provide more insights into the underlying
      evolution mechanisms of trees acclimating to their natural habitat.

PMID- 22957201
TI  - Abnormally high digestive enzyme activity and gene expression explain the
      contemporary evolution of a Diabrotica biotype able to feed on soybeans.
AB  - Western corn rootworm (Diabrotica virgifera) (WCR) depends on the continuous
      availability of corn. Broad adoption of annual crop rotation between corn (Zea
      mays) and nonhost soybean (Glycine max) exploited WCR biology to provide
      excellent WCR control, but this practice dramatically reduced landscape
      heterogeneity in East-central Illinois and imposed intense selection pressure.
      This selection resulted in behavioral changes and "rotation-resistant" (RR) WCR
      adults. Although soybeans are well defended against Coleopteran insects by
      cysteine protease inhibitors, RR-WCR feed on soybean foliage and remain long
      enough to deposit eggs that will hatch the following spring and larvae will feed
      on roots of planted corn. Other than documenting changes in insect mobility and
      egg laying behavior, 15 years of research have failed to identify any diagnostic
      differences between wild-type (WT)- and RR-WCR or a mechanism that allows for
      prolonged RR-WCR feeding and survival in soybean fields. We documented
      differences in behavior, physiology, digestive protease activity (threefold to
      fourfold increases), and protease gene expression in the gut of RR-WCR adults.
      Our data suggest that higher constitutive activity levels of cathepsin L are part
      of the mechanism that enables populations of WCR to circumvent soybean defenses,
      and thus, crop rotation. These new insights into the mechanism of WCR tolerance
      of soybean herbivory transcend the issue of RR-WCR diagnostics and management to
      link changes in insect gut proteolytic activity and behavior with landscape
      heterogeneity. The RR-WCR illustrates how agro-ecological factors can affect the
      evolution of insects in human-altered ecosystems.

PMID- 22957202
TI  - Genetic variability in geographic populations of the natterjack toad (Bufo
      calamita).
AB  - Across altitudinal and latitudinal gradients, the proportion of suitable habitats
      varies, influencing the individual dispersal that ultimately can produce
      differentiation among populations. The natterjack toad (Bufo calamita) is
      distributed across a wide geographic range that qualifies the species as
      interesting for a geographic analysis of its genetic variability. Five
      populations of B. calamita in the Sierra de Gredos (Spain) were studied in an
      altitudinal gradient ranging from 750 to 2270 m using microsatellite markers. In
      addition, we analyzed the latitudinal genetic variation in B. calamita within a
      global European distribution using genetic diversity parameters (mean number of
      alleles per locus [M(a)] and expected heterozygosity [H(E)]) obtained from our
      results and those published in the literature. The low level of genetic
      differentiation found between populations of B. calamita (F(st) ranging from
      0.0115 to 0.1018) and the decreases in genetic diversity with altitude (M(a) from
      13.6 to 8.3, H(E) from 0.82 to 0.74) can be interpreted by the combined effects
      of discontinuous habitat, produced mainly by the high slopes barriers and
      geographic distance. In the latitudinal gradient, genetic diversity decreases
      from south to north as a consequence of the colonization of the species from the
      Pleistocene refugium. We conclude that the genetic variability in B. calamita
      along its wide altitudinal and latitudinal geographic distribution mainly
      reflects the colonization history of the species after the last glacial period.

PMID- 22957203
TI  - The genetics of phenotypic plasticity. XI. Joint evolution of plasticity and
      dispersal rate.
AB  - In a spatially heterogeneous environment, the rate at which individuals move
      among habitats affects whether selection favors phenotypic plasticity or genetic
      differentiation, with high dispersal rates favoring trait plasticity. Until now,
      in theoretical explorations of plasticity evolution, dispersal rate has been
      treated as a fixed, albeit probabilistic, characteristic of a population, raising
      the question of what happens when the propensity to disperse and trait plasticity
      are allowed to evolve jointly. We examined the effects of their joint evolution
      on selection for plasticity using an individual-based computer simulation model.
      In the model, the environment consisted of a linear gradient of 50 demes with
      dispersal occurring either before or after selection. Individuals consisted of
      loci whose phenotypic expression either are affected by the environment (plastic)
      or are not affected (nonplastic), plus a locus determining the propensity to
      disperse. When dispersal rate and trait plasticity evolve jointly, the system
      tends to dichotomous outcomes of either high trait plasticity and high dispersal,
      or low trait plasticity and low dispersal. The outcome strongly depended on
      starting conditions, with high trait plasticity and dispersal favored when the
      system started at high values for either trait plasticity or dispersal rate (or
      both). Adding a cost of plasticity tended to drive the system to genetic
      differentiation, although this effect also depended on initial conditions.
      Genetic linkage between trait plasticity loci and dispersal loci further enhanced
      this strong dichotomy in evolutionary outcomes. All of these effects depended on
      organismal life history pattern, and in particular whether selection occurred
      before or after dispersal. These results can explain why adaptive trait
      plasticity is less common than might be expected.

PMID- 22957204
TI  - The disappearing northern leopard frog (Lithobates pipiens): conservation
      genetics and implications for remnant populations in western Nevada.
AB  - Global amphibian declines suggest a major shift in the amount and quality of
      habitat for these sensitive taxa. Many species that were once widespread are now
      experiencing declines either in part of or across their historic range. The
      northern leopard frog (Rana [Lithobates] pipiens] has undergone significant
      declines particularly in the western United States and Canada. Leopard frog
      population losses in Nevada are largely due to habitat fragmentation and the
      introduction of nonnative fish, amphibian, and plant species. Only two
      populations remain in the Truckee and Carson River watersheds of western Nevada
      which represents the western boundary of this species range. We used sequence
      data for an 812 base pair fragment of the mitochondrial NADH dehydrogenase 1
      (ND1) gene to support a native origin for western Nevada populations. All frogs
      had a single haplotype (W07) from the distinct western North America ND1
      haplotype clade. Data from seven polymorphic microsatellite loci show that
      Truckee and Carson River populations are highly differentiated from each other
      and from leopard frogs collected from eastern Nevada sites. Lack of gene flow
      among and distinct color morphs among the western Nevada populations likely
      predates the current geographical isolation. Comparisons with other peripheral L.
      pipiens populations show western Nevada populations have similar levels of gene
      diversity despite their contemporary isolation (H(E) 0.411, 0.482). Restoration
      of leopard frog populations in these watersheds will be challenging given well
      entrenched nonnative bullfrog populations and major changes to the riparian zone
      over the past century. Declines of once common amphibian species has become a
      major conservation concern. Contemporary isolation of populations on a species
      range periphery such as the leopard frog populations in the Truckee and Carson
      rivers further exacerbate extirpation risk as these populations are likely to
      have fewer genetic resources to adaptively respond to rapidly changing biotic and
      abiotic environments.

PMID- 22957205
TI  - Genetic analysis of Black Tiger shrimp (Penaeus monodon) across its natural
      distribution range reveals more recent colonization of Fiji and other South
      Pacific islands.
AB  - The Black Tiger shrimp (Penaeus monodon) has a natural distribution range from
      East Africa to the South Pacific Islands. Although previous studies of Indo
      Pacific P. monodon have found populations from the Indian Ocean and Australasia
      to differ genetically, their relatedness to South Pacific shrimp remains unknown.
      To address this, polymorphisms at eight shared microsatellite loci and haplotypes
      in a 418-bp mtDNA-CR (control region) sequence were examined across 682 P.
      monodon from locations spread widely across its natural range, including the
      South Pacific islands of Fiji, Palau, and Papua New Guinea (PNG). Observed
      microsatellite heterozygosities of 0.82-0.91, allele richness of 6.85-9.69, and
      significant mtDNA-CR haplotype variation indicated high levels of genetic
      diversity among the South Pacific shrimp. Analysis of microsatellite genotypes
      using a Bayesian STRUCTURE method segregated Indo-Pacific P. monodon into eight
      distinct clades, with Palau and PNG shrimp clustering among others from Southeast
      Asia and eastern Australia, respectively, and Fiji shrimp clustering as a
      distinct group. Phylogenetic analyses of mtDNA-CR haplotypes delineated shrimp
      into three groupings, with shrimp from Fiji again being distinct by sharing no
      haplotypes with other populations. Depending on regional location, the genetic
      structures and substructures identified from the genotyping and mtDNA-CR
      haplotype phylogeny could be explained by Metapopulation and/or Member-Vagrant
      type evolutionary processes. Neutrality tests of mutation-drift equilibrium and
      estimation of the time since population expansion supported a hypothesis that
      South Pacific P. monodon were colonized from Southeast Asia and eastern Australia
      during the Pleistocene period over 60,000 years ago when land bridges were more
      expansive and linked these regions more closely.

PMID- 22957206
TI  - Pacific Walrus and climate change: observations and predictions.
AB  - The extent and duration of sea-ice habitats used by Pacific walrus (Odobenus
      rosmarus divergens) are diminishing resulting in altered walrus behavior,
      mortality, and distribution. I document changes that have occurred over the past
      several decades and make predictions to the end of the 21st century. Climate
      models project that sea ice will monotonically decline resulting in more ice-free
      summers of longer duration. Several stressors that may impact walruses are
      directly influenced by sea ice. How these stressors materialize were modeled as
      most likely-case, worst-case, and best-case scenarios for the mid- and late-21st
      century, resulting in four comprehensive working hypotheses that can help
      identify and prioritize management and research projects, identify comprehensive
      mitigation actions, and guide monitoring programs to track future developments
      and adjust programs as needed. In the short term, the most plausible hypotheses
      predict a continuing northward shift in walrus distribution, increasing use of
      coastal haulouts in summer and fall, and a population reduction set by the
      carrying capacity of the near shore environment and subsistence hunting.
      Alternatively, under worst-case conditions, the population will decline to a
      level where the probability of extinction is high. In the long term, walrus may
      seasonally abandon the Bering and Chukchi Seas for sea-ice refugia to the
      northwest and northeast, ocean warming and pH decline alter walrus food
      resources, and subsistence hunting exacerbates a large population decline.
      However, conditions that reverse current trends in sea ice loss cannot be ruled
      out. Which hypothesis comes to fruition depends on how the stressors develop and
      the success of mitigation measures. Best-case scenarios indicate that successful
      mitigation of unsustainable harvests and terrestrial haulout-related mortalities
      can be effective. Management and research should focus on monitoring, elucidating
      effects, and mitigation, while ultimately, reductions in greenhouse gas emissions
      are needed to reduce sea-ice habitat losses.

PMID- 22957209
TI  - Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes.
AB  - Directed evolution of proteins is a technique used to modify protein functions
      through "Darwinian selection." In vitro compartmentalization (IVC) is an in vitro
      gene screening system for directed evolution of proteins. IVC establishes the
      link between genetic information (genotype) and the protein translated from the
      information (phenotype), which is essential for all directed evolution methods,
      by encapsulating both in a nonliving microcompartment. Herein, we introduce a new
      liposome-based IVC system consisting of a liposome, the protein synthesis using
      recombinant elements (PURE) system and a fluorescence-activated cell sorter
      (FACS) used as a microcompartment, in vitro protein synthesis system, and high
      throughput screen, respectively. Liposome-based IVC is characterized by in vitro
      protein synthesis from a single copy of a gene in a cell-sized unilamellar
      liposome and quantitative functional evaluation of the synthesized proteins.
      Examples of liposome-based IVC for screening proteins such as GFP and beta
      glucuronidase are described. We discuss the future directions for this method and
      its applications.

PMID- 22957208
TI  - Polyamine metabolism in fungi with emphasis on phytopathogenic species.
AB  - Polyamines are essential metabolites present in all living organisms, and this
      subject has attracted the attention of researchers worldwide interested in
      defining their mode of action in the variable cell functions in which they are
      involved, from growth to development and differentiation. Although the mechanism
      of polyamine synthesis is almost universal, different biological groups show
      interesting differences in this aspect that require to be further analyzed. For
      these studies, fungi represent interesting models because of their
      characteristics and facility of analysis. During the last decades fungi have
      contributed to the understanding of polyamine metabolism. The use of specific
      inhibitors and the isolation of mutants have allowed the manipulation of the
      pathway providing information on its regulation. During host-fungus interaction
      polyamine metabolism suffers striking changes in response to infection, which
      requires examination. Additionally the role of polyamine transporter is getting
      importance because of its role in polyamine regulation. In this paper we analyze
      the metabolism of polyamines in fungi, and the difference of this process with
      other biological groups. Of particular importance is the difference of polyamine
      biosynthesis between fungi and plants, which makes this process an attractive
      target for the control of phytopathogenic fungi.

PMID- 22957210
TI  - Combinatorial Synthesis, Screening, and Binding Studies of Highly Functionalized
      Polyamino-amido Oligomers for Binding to Folded RNA.
AB  - Folded RNA molecules have recently emerged as critical regulatory elements in
      biological pathways, serving not just as carriers of genetic information but also
      as key components in enzymatic assemblies. In particular, the transactivation
      response element (TAR) of the HIV genome regulates transcriptional elongation by
      interacting specifically with the Tat protein, initiating the recruitment of the
      elongation complex. Preventing this interaction from occurring in vivo halts HIV
      replication, thus making RNA-binding molecules an intriguing pharmaceutical
      target. Using alpha-amino acids as starting materials, we have designed and
      synthesized a new class of polyamino-amido oligomers, called PAAs, specifically
      for binding to folded RNA structures. The PAA monomers were readily incorporated
      into a 125-member combinatorial library of PAA trimers. In order to rapidly
      assess RNA binding, a quantum dot-based fluorescent screen was developed to
      visualize RNA binding on-resin. The binding affinities of hits were quantified
      using a terbium footprinting assay, allowing us to identify a ligand (SFF) with
      low micromolar affinity (k(d) = 14 MUM) for TAR RNA. The work presented herein
      represents the development of a flexible scaffold that can be easily synthesized,
      screened, and subsequently modified to provide ligands specific for binding to
      folded RNAs.

PMID- 22957211
TI  - Association of aldosterone and cortisol with cardiovascular risk factors in
      prehypertension stage.
AB  - Background. The Pakistani population has higher incidence of cardiovascular (CV)
      diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN). A
      variety of associated HTN stressors is also reported. The study plans to
      understand the variables associated with initiation of HTN in this population.
      Objective. To find plasma aldosterone and cortisol relationship with some CV risk
      factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium) in different
      stages of HTN particularly prehypertension. Subjects and Methods. The study
      conducted on 276 subjects (25-60 years), classified into prehypertensive (n =
      55), HTN stage-1 (n = 70) and II (n = 76) according to 7th JNC report and
      compared with normotensive controls (n = 75). The anthropometric profiles
      (height, weight, waist circumference, Body Mass index) and BP recorded. Serum
      cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood
      glucose, Na(+) and K(+), using standard laboratory techniques, were determined in
      fasting blood samples. Results. Subjects were mostly overweight and obese (80%,
      90%, and 76% in pre-HTN, stage-I and II versus 69% in controls). The aldosterone
      level (ng/dl) was in higher normal range (9.17-12.41) and significantly
      correlated to BMI (0.587) in controls, and to TC (0.726) and LDL (0.620) in pre
      HTN stage-I. The cortisol level was positively correlated (P < 0.01) to BMI
      (0.538), Na(+) (0.690) and K(+) (0.578) in control, and to BMI (0.628) and WC
      (0.679) in pre-HTN group, showing its association with BMI > 25. Conclusion. Pre
      HTN stage among Pakistani population with successive increase in various risk
      factors of HTN in relation to aldosterone and cortisol has been identified.
      Interaction of the risk factors with endogenous levels of these hormones may
      initiate stages of HTN.

PMID- 22957212
TI  - Experiences in Developing and Implementing Health Clubs to Reduce Hypertension
      Risk among Adults in a South African Population in Transition.
AB  - Chronic noncommunicable diseases (NCDs) are increasing substantially as a cause
      of death and disability in all strata of the South African society, particularly
      among the urbanised poor. Hypertension is a risk factor for many of these
      diseases and becoming a burden in a growing population in a Cape Town township,
      Khayelitsha. To alleviate healthcare demands at clinics in this area, a health
      club was initiated and community health workers (CHWs) were trained to empower
      community members about NCDs and create public awareness. After training, a
      health club was initiated. Three months after initiation of the health club, 76
      participants had been recruited of whom 22 were regular attenders. New members
      joined the health club weekly. Anthropometric and blood pressure measurements
      were taken, and various hypertension topics were covered at the club meetings
      which included healthy behaviours, such as the benefits of being physically
      active and eating healthy. Nutrition education sessions based on the South
      African food-based dietary guidelines were also held. Consequent to the initial
      group that was established, two more clubs were formed in the area. Health clubs
      are sustainable and culturally appropriate when facilitated by local people who
      have an insight and deeper understanding of the culture and environment of the
      people they serve.

PMID- 22957213
TI  - Vascular disease in systemic lupus erythematosus.
AB  - Vascular disease, either as a direct complication of the disease or developing as
      an accompanying comorbidity impairs significantly the quality of life of patients
      with SLE and represents the most frequent cause of death in established lupus.
      This paper aims to give an overview of the prevalence of the different forms of
      vasculopathy that can be encountered in a lupus patient, describe their
      pathogenesis, and address their impact on disease severity and outcome.

PMID- 22957214
TI  - Behavioral determinants of obesity: research findings and policy implications.

PMID- 22957215
TI  - An update on less invasive and endoscopic techniques mimicking the effect of
      bariatric surgery.
AB  - Obesity (BMI 30-35 kg/m(2)) and its associated disorders such as type 2 diabetes,
      nonalcoholic fatty liver disease, and cardiovascular disease have reached
      pandemic proportions worldwide. For the morbidly obese population (BMI 35-50
      kg/m(2)), bariatric surgery has proven to be the most effective treatment to
      achieve significant and sustained weight loss, with concomitant positive effects
      on the metabolic syndrome. However, only a minor percentage of eligible
      candidates are treated by means of bariatric surgery. In addition, the expanding
      obesity epidemic consists mostly of relatively less obese patients who are not
      (yet) eligible for bariatric surgery. Hence, less invasive techniques and devices
      are rapidly being developed. These novel entities mimic several aspects of
      bariatric surgery either by gastric restriction (gastric balloons, gastric
      plication), by influencing gastric function (gastric botulinum injections,
      gastric pacing, and vagal nerve stimulation), or by partial exclusion of the
      small intestine (duodenal-jejunal sleeve). In the last decade, several novel less
      invasive techniques have been introduced and some have been abandoned again. The
      aim of this paper is to discuss the safety, efficacy, complications,
      reversibility, and long-term results of these latest developments in the
      treatment of obesity.

PMID- 22957217
TI  - Overweight and Obese Children's Ability to Report Energy Intake Using Digital
      Camera Food Records during a 2-Year Study.
AB  - The objective was to evaluate overweight and obese children's ability to report
      reproducible and valid estimates of energy intake (EI) by using digital camera
      food records (FR) during a 2-year study, compared with objectively measured total
      energy expenditure (TEE). Seventy-three overweight/obese children, aged 8-12
      years at inclusion, kept FR with the help of digital cameras for 16 days in
      total, on 7 occasions during a 2-year period. On the same days, their TEE was
      registered with SenseWear Armband (SWA). The children underestimated their EI by 
      2.8 (2.4) MJ/d on the first assessment occasion (95% CI: -3.3, -2.3). Reporting
      accuracy did not differ between the 7 assessment occasions (P = 0.15). Variables
      negatively associated with reporting accuracy relative to TEE were increased age
      (95% CI: -0.07, -0.01) and BMI z-score (95% CI: -0.18, -0.06). Further, reporting
      accuracy relative to TEE was lower for girls than boys (95% CI: -0.14, -0.01) and
      on weekdays compared with weekend days (95% CI: -0.08, -0.001). In conclusion,
      overweight and obese children were able to report their EI using a digital camera
      FR with good reproducibility over a 2-year period, even though their EI was
      underestimated compared with objectively measured TEE.

PMID- 22957216
TI  - Childhood obesity and obstructive sleep apnea.
AB  - The global epidemic of childhood and adolescent obesity and its immediate as well
      as long-term consequences for obese individuals and society as a whole cannot be
      overemphasized. Obesity in childhood and adolescence is associated with an
      increased risk of adult obesity and clinically significant consequences affecting
      the cardiovascular and metabolic systems. Importantly, obesity is additionally
      complicated by obstructive sleep apnea (OSA), occurring in up to 60% of obese
      children. OSA, which is diagnosed using the gold standard polysomnogram (PSG), is
      characterised by snoring, recurrent partial (hypopneas) or complete (apneas)
      obstruction of the upper airway. OSA is frequently associated with intermittent
      oxyhemoglobin desaturations, sleep disruption, and sleep fragmentation. There is
      emerging data that OSA is associated with cardiovascular burden including
      systemic hypertension, changes in ventricular structure and function, arterial
      stiffness, and metabolic syndromes. Thus, OSA in the context of obesity may
      independently or synergistically magnify the underlying cardiovascular and
      metabolic burden. This is of importance as early recognition and treatment of OSA
      in obese children are likely to result in the reduction of cardiometabolic burden
      in obese children. This paper summarizes the current state of understanding of
      obesity-related OSA. Specifically, this paper will discuss epidemiology,
      pathophysiology, cardiometabolic burden, and management of obese children and
      adolescents with OSA.

PMID- 22957218
TI  - Estimates of total dietary folic Acid intake in the Australian population
      following mandatory folic Acid fortification of bread.
AB  - Mandatory folic acid fortification of wheat flour for making bread was
      implemented in Australia in September 2009, to improve the dietary folate status
      of women of child-bearing age, and help reduce the incidence of neural tube
      defects in the population. This paper presents estimates of folic acid intake in
      the target population and other subgroups of the Australian population following
      implementation of the mandatory folic acid fortification standard. In June/July
      2010 one hundred samples from seven bread categories were purchased from around
      the country and individually analysed for the amount of folic acid they
      contained. A modification to the triple enzyme microbiological method was used to
      measure folic acid in the individual bread samples. The folic acid analytical
      values together with national food consumption data were used to generate
      estimates of the population's folic acid intake from fortified foods. Food
      Standards Australia New Zealand's (FSANZ) custom-built dietary modelling program
      (DIAMOND) was used for the estimates. The mean amount of folic acid found in
      white bread was 200 MUg/100 g which demonstrated that folic-acid-fortified wheat
      flour was used to bake the bread. The intake estimates indicated an increase in
      mean folic acid intake of 159 MUg per day for the target group. Other sub-groups
      of the population also showed increases in estimated mean daily intake of folic
      acid.

PMID- 22957219
TI  - Sources of Dietary Fiber and the Association of Fiber Intake with Childhood
      Obesity Risk (in 2-18 Year Olds) and Diabetes Risk of Adolescents 12-18 Year
      Olds: NHANES 2003-2006.
AB  - Increased fiber intake has been linked with lower risk of overweight and obesity
      in adults, but data are sparse for children. To address this issue, NHANES 2003
      2006 data was used to evaluate (1) the food sources of fiber in children, (2) the
      dietary fiber density levels and risk of being classified as overweight/obese,
      and (3) the association between fiber intake level and impaired glucose
      metabolism in children. Analyses were restricted to the subsample of children
      with biological plausible diet reports (N = 4,667) and stratified by 2-11 year
      olds (n = 2072) and 12-18 year olds (n = 2595). Results showed that the food
      sources are predominantly foods that are low in dietary fiber, but are consumed
      at high levels. In 2-18 year old plausible reporters, the risk for
      overweight/obesity decreased by 17% from children in the medium tertile of fiber
      density intake compared to the lowest tertile (OR = 0.83, P value = 0.043) and by
      21% between the highest compared to the lowest tertile (OR = 0.79, P value =
      0.031). There was a protective effect of being in the medium tertile of dietary
      fiber density (OR = 0.68, P value <0.001) on impaired glucose metabolism. These
      results indicate a beneficial effect of higher fiber density in children's diets.

PMID- 22957220
TI  - Virological Response in Cerebrospinal Fluid to Antiretroviral Therapy in a Large
      Italian Cohort of HIV-Infected Patients with Neurological Disorders.
AB  - The aim of the present study was to analyse the effect of antiretroviral (ARV)
      therapy and single antiretroviral drugs on cerebrospinal fluid (CSF) HIV-RNA
      burden in HIV-infected patients affected by neurological disorders enrolled in a
      multicentric Italian cohort. ARVs were considered "neuroactive" from literature
      reports. Three hundred sixty-three HIV-positive patients with available data from
      paired plasma and CSF samples, were selected. One hundred twenty patients (33.1%)
      were taking ARVs at diagnosis of neurological disorder. Mean CSF HIV-RNA was
      significantly higher in naive than in experienced patients, and in patients not
      taking ARV than in those on ARV. A linear correlation between CSF HIV-RNA levels
      and number of neuroactive drugs included in the regimen was also found (r = 
      0.44, P < 0.001). Low -plasma HIV-RNA and the lack of neurocognitive impairment
      resulted in independently associated to undetectable HIV-RNA. Taking nevirapine
      or efavirenz, or regimen including NNRTI, NNRTI plus PI or boosted PI, was
      independently associated to an increased probability to have undetectable HIV-RNA
      in CSF. The inclusion of two or three neuroactive drugs in the ARV regimen was
      independently associated to undetectable viral load in CSF. Our data could be
      helpful in identifying ARV regimens able to better control HIV replication in the
      CNS sanctuary, and could be a historical reference for further analyses.

PMID- 22957221
TI  - Sickle cell disease: genetics, cellular and molecular mechanisms, and therapies.

PMID- 22957223
TI  - Respiratory Impairment after Early Red Cell Transfusion in Pediatric Patients
      with ALI/ARDS.
AB  - Introduction. In the first 48 hours of ventilating patients with acute lung
      injury (ALI)/acute respiratory distress syndrome (ARDS), a multipronged approach
      including packed red blood cell (PRBC) transfusion is undertaken to maintain
      oxygen delivery. Hypothesis. We hypothesized children with ALI/ARDS transfused
      within 48 hours of initiating mechanical ventilation would have worse outcome.
      The course of 34 transfused patients was retrospectively compared to 45
      nontransfused control patients admitted to the PICU at Helen DeVos Children's
      Hospital between January 1st 2008 and December 31st 2009. Results. Mean
      hemoglobin (Hb) prior to transfusion was 8.2 g/dl compared to 10.1 g/dl in
      control. P/F ratio decreased from 135.4 +/- 7.5 to 116.5 +/- 8.8 in transfused
      but increased from 148.0 +/- 8.0 to 190.4 +/- 17.8 (P < 0.001) in control. OI
      increased in the transfused from 11.7 +/- 0.9 to 18.7 +/- 1.6 but not in control.
      Ventilator days in the transfused were 15.6 +/- 1.7 versus 9.5 +/- 0.6 days in
      control (P < 0.001). There was a trend towards higher rates of MODS in transfused
      patients; 29.4% versus 17.7%, odds ratio 1.92, 95% CI; 0.6-5.6 Fisher exact P <
      0.282. Conclusion. This study suggests that early transfusions of patients with
      ALI/ARDS were associated with increased ventilatory needs.

PMID- 22957222
TI  - Immune response to lipoproteins in atherosclerosis.
AB  - Atherosclerosis, the underlying cause of cardiovascular disease, is characterized
      by chronic inflammation and altered immune response. Cholesterol is a well-known
      risk factor associated with the development of cardiovascular diseases. Elevated
      serum cholesterol is unique because it can lead to development of atherosclerosis
      in animals and humans even in the absence of other risk factors. Modifications of
      low-density lipoproteins mediated by oxidation, enzymatic degradation, and
      aggregation result in changes in their function and activate both innate and
      adaptive immune system. Oxidized low-density lipoprotein (LDL) has been
      identified as one of the most important autoantigens in atherosclerosis. This
      escape from self-tolerance is dependent on the formation of oxidized
      phospholipids. The emerging understanding of the importance of immune responses
      against oxidized LDL in atherosclerosis has focused attention on the possibility
      of development of novel therapy for atherosclerosis. This review provides an
      overview of immune response to lipoproteins and the fascinating possibility of
      developing an immunomodulatory therapy for atherosclerosis.

PMID- 22957224
TI  - Goal-oriented respiratory management for critically ill patients with acute
      respiratory distress syndrome.
AB  - This paper, based on relevant literature articles and the authors' clinical
      experience, presents a goal-oriented respiratory management for critically ill
      patients with acute respiratory distress syndrome (ARDS) that can help improve
      clinicians' ability to care for these patients. Early recognition of ARDS
      modified risk factors and avoidance of aggravating factors during hospital stay
      such as nonprotective mechanical ventilation, multiple blood products
      transfusions, positive fluid balance, ventilator-associated pneumonia, and
      gastric aspiration can help decrease its incidence. An early extensive clinical,
      laboratory, and imaging evaluation of "at risk patients" allows a correct
      diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic
      indices, so that a careful treatment can be planned. Rapid administration of
      antibiotics and resuscitative measures in case of sepsis and septic shock
      associated with protective ventilatory strategies and early short-term paralysis
      associated with differential ventilatory techniques (recruitment maneuvers with
      adequate positive end-expiratory pressure titration, prone position, and new
      extracorporeal membrane oxygenation techniques) in severe ARDS can help improve
      its prognosis. Revaluation of ARDS patients on the third day of evolution
      (Sequential Organ Failure Assessment (SOFA), biomarkers and response to infection
      therapy) allows changes in the initial treatment plans and can help decrease ARDS
      mortality.

PMID- 22957225
TI  - Effects of temperament and character profiles on state and trait depression and
      anxiety: a prospective study of a Japanese youth population.
AB  - Objective. To examine the effects of temperament and character profiles on state
      and trait depression and anxiety in a Japanese youth population. Method. Japanese
      university students were solicited for participation in a two-wave study, with
      assessments performed at Time 1 (T1) and Time 2 (T2), separated by a five-month
      interval. A total of 184 students completed the Japanese version of the
      temperament and character inventory (TCI) at T1 and the Hospital Anxiety and
      Depression Scale (HADS) at T1 and T2. We posited two latent variables, trait
      depression and anxiety, composed of the T1 and T2 HADS depression and anxiety
      scores, respectively. We also posited that temperament domain traits would
      predict character domain traits, and that all the personality traits would be
      linked to trait depression and anxiety and also predict T2 depression and
      anxiety. Results. Structural regression modeling showed that (1) only high
      Novelty Seeking predicted T2 Anxiety score, (2) trait depression and anxiety were
      linked to high harm avoidance and low self-directedness, and (3) trait depression
      was linked to high self-transcendence whereas trait anxiety was linked to low
      reward dependence, persistence, and cooperativeness. Conclusion. The
      characteristic associations between TCI subscales and depression and anxiety were
      limited to the trait rather than state aspects of depression and anxiety.

PMID- 22957226
TI  - Atypical febrile seizures, mesial temporal lobe epilepsy, and dual pathology.
AB  - Febrile seizures occurring in the neonatal period, especially when prolonged, are
      thought to be involved in the later development of mesial temporal lobe epilepsy
      (mTLE) in children. The presence of an often undetected, underlying cortical
      malformation has also been reported to be implicated in the epileptogenesis
      process following febrile seizures. This paper highlights some of the various
      animal models of febrile seizures and of cortical malformation and portrays a two
      hit model that efficiently mimics these two insults and leads to spontaneous
      recurrent seizures in adult rats. Potential mechanisms are further proposed to
      explain how these two insults may each, or together, contribute to network
      hyperexcitability and epileptogenesis. Finally the clinical relevance of the two
      hit model is briefly discussed in light of a therapeutic and preventive approach
      to mTLE.

PMID- 22957227
TI  - Postoperative neuropsychological outcome in patients with mesial temporal lobe
      epilepsy in Argentina.
AB  - The aim of the present study is to compare pre- and postsurgical
      neuropsychological outcome in individuals suffering from mesial temporal lobe
      epilepsy (mTLE), in order to evaluate prognosis. The selected thirty-five
      patients had medically mTLE and had undergone an anterior temporal lobectomy
      (ATL). Neuropsychological evaluation was performed in three different stages:
      before ATL, 6 months after resection, and a year afterwards. Neuropsychological
      protocol evaluated attention, verbal memory, visual memory, executive function,
      language, intelligence, and handedness. There was a significant improvement (P =
      0.030) in the group with visual memory deficit after surgery, whereas no changes
      were observed across patients with verbal memory deficit. No changes were
      observed in language after surgery. Executive function showed significant
      improvement 6 months after surgery (P = 0.035). Postoperative outcome of
      cognitive impairments depends on baseline neuropsychological status of the
      patients with TLE. In our case series, deficits found in patients with mTLE after
      ATL did not result in a subjective complaint.

PMID- 22957228
TI  - Surgical techniques for the treatment of temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is the most common form of medically intractable
      epilepsy. Advances in electrophysiology and neuroimaging have led to a more
      precise localization of the epileptogenic zone within the temporal lobe.
      Resective surgery is the most effective treatment for TLE. Despite the
      variability in surgical techniques and in the extent of resection, the overall
      outcomes of different TLE surgeries are similar. Here, we review different
      surgical interventions for the management of TLE.

PMID- 22957229
TI  - Selective amygdalohippocampectomy.
AB  - Epilepsy surgery can be an effective epilepsy treatment for patients whose
      seizures do not respond to best medical therapy. For patients with temporal lobe
      epilepsy, selective amygdalohippocampectomy (SAH) has emerged as a viable
      alternative to standard anterior temporal lobectomy. This paper reviews the
      indications for SAH, the technical advances that have led to greater adoption of
      the procedure, the expectations for seizure control, and the risks of morbidity.

PMID- 22957230
TI  - Spontaneous EEG-Functional MRI in Mesial Temporal Lobe Epilepsy: Implications for
      the Neural Correlates of Consciousness.
AB  - The combination of electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) has been shown to have great potential for providing a greater
      understanding of normal and diseased states in both human and animal studies.
      Simultaneous EEG-fMRI is particularly well suited for the study of epilepsy in
      that it may reveal the neurobiology of ictal and interictal epileptiform
      discharges and noninvasively localize epileptogenic foci. Spontaneous, coherent
      fluctuations of neuronal activity and the coupled hemodynamic responses have also
      been shown to provide diagnostic markers of disease, extending our understanding
      of intrinsically structured ongoing brain activity. Following a short summary of
      the hardware and software development of simultaneous EEG-fMRI, this paper
      reviews a unified framework of integrating neuronal and hemodynamic processes
      during epileptic seizures and discusses the role and impact of spontaneous
      activity in the mesial temporal lobe epilepsies with particular emphasis on the
      neural and physiological correlates of consciousness.

PMID- 22957231
TI  - Deja experiences in temporal lobe epilepsy.
AB  - Historically, deja vu has been linked to seizure activity in temporal lobe
      epilepsy, and clinical reports suggest that many patients experience the
      phenomenon as a manifestation of simple partial seizures. We review studies on
      deja vu in epilepsy with reference to recent advances in the understanding of
      deja vu from a cognitive and neuropsychological standpoint. We propose a
      decoupled familiarity hypothesis, whereby deja vu is produced by an erroneous
      feeling of familiarity which is not in keeping with current cognitive processing.
      Our hypothesis converges on a parahippocampal dysfunction as the locus of deja vu
      experiences. However, several other temporal lobe structures feature in reports
      of deja vu in epilepsy. We suggest that some of the inconsistency in the
      literature derives from a poor classification of the various types of deja
      experiences. We propose deja vu/deja vecu as one way of understanding deja
      experiences more fully. This distinction is based on current models of memory
      function, where deja vu is caused by erroneous familiarity and deja vecu by
      erroneous recollection. Priorities for future research and clinical issues are
      discussed.

PMID- 22957232
TI  - Establishment of a comprehensive epilepsy center in pakistan: initial
      experiences, results, and reflections.
AB  - Background. Developing countries, home to 80% of epilepsy patients, do not have
      comprehensive epilepsy surgery programs. Considering these needs we set up first
      epilepsy surgery center in Pakistan. Methods. Seventeen teleconferences focused
      on setting up an epilepsy center at the Aga Khan University (AKU), Karachi,
      Pakistan were arranged with experts from the University of Alberta Hospital,
      Alberta, Canada and the University of West Virginia, USA over a two-year period.
      Subsequently, the experts visited the proposed center to provide hands on
      training. During this period several interactive teaching sessions, a nationwide
      workshop, and various public awareness events were organized. Results. Sixteen
      patients underwent surgery, functional hemispherectomy (HS) was done in six,
      anterior temporal lobectomy (ATL) in six, and neuronavigation-guided selective
      amygdalohippocampectomy (SAH) using keyhole technique in four patients. Minimal
      morbidity was observed in ATL and, SAH groups. All patients in SAH group (100%)
      had Grade 1 control, while only 5 patients (83%) in ATL group, and 4 patients
      (66%) in HS group had Grade 1 control according to Engel's classification, in
      average followups of 12 months, 24 months and 48 months for SAH, ATL, and HS,
      respectively. Conclusion. As we share our experience we hope to set a practical
      example for economically constrained countries that successful epilepsy surgery
      centers can be managed with limited resources.

PMID- 22957233
TI  - Neuropathology of temporal lobe epilepsy.
AB  - Pathologic findings in surgical resections from patients with temporal lobe
      epilepsy include a wide range of diagnostic possibilities that can be categorized
      into different groups on the basis of etiology. This paper outlines the various
      pathologic entities described in temporal lobe epilepsy, including some newly
      recognized epilepsy-associated tumors, and briefly touch on the recent
      classification of focal cortical dysplasia. This classification takes into
      account coexistent pathologic lesions in focal cortical dysplasia.

PMID- 22957234
TI  - A review of the epidemiology of temporal lobe epilepsy.
AB  - Partial-onset epilepsies account for about 60% of all adult epilepsy cases, and
      temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred
      for epilepsy surgery and often refractory to antiepileptic drugs (AEDs). Little
      is known about the epidemiology of TLE, because it requires advanced
      neuroimaging, positive EEG, and appropriate clinical semiology to confirm the
      diagnosis. Moreover, recently recognized incidentally detected mesial temporal
      sclerosis in otherwise healthy individuals and benign temporal epilepsy indicate
      that the true epidemiology of TLE is underestimated. Our current knowledge on the
      epidemiology of TLE derives from data published from tertiary referral centers
      and/or inferred from population-based studies dealing with epilepsy. This article
      reviews the following aspects of the epidemiology of TLE: definitions, studies
      describing epidemiological rates, methodological observations, the interpretation
      of available studies, and recommendations for future studies.

PMID- 22957236
TI  - Temporal lobe epilepsy in the elderly.
AB  - The incidence of epilepsy has bimodal distribution peaking at the extremes of
      life. Incidence is greater in younger and older age groups (Hauser et al., 1993,
      Sidenvall et al., 1993, Forsgren et al., 1996, and Olafsson et al., 2005). As the
      world population ages more elders with epilepsy will be identified. In the high
      income countries with longer life expectancy, the number of elders with epilepsy
      will be even higher. CPSs account for 40% of all seizure types in the elderly
      (Hauser et al., 1992); however, the proportion with temporal lobe epilepsy (TLE)
      is uncertain.

PMID- 22957235
TI  - Electroencephalography in mesial temporal lobe epilepsy: a review.
AB  - Electroencephalography (EEG) has an important role in the diagnosis and
      classification of epilepsy. It can provide information for predicting the
      response to antiseizure drugs and to identify the surgically remediable
      epilepsies. In temporal lobe epilepsy (TLE) seizures could originate in the
      medial or lateral neocortical temporal region, and many of these patients are
      refractory to medical treatment. However, majority of patients have had excellent
      results after surgery and this often relies on the EEG and magnetic resonance
      imaging (MRI) data in presurgical evaluation. If the scalp EEG data is
      insufficient or discordant, invasive EEG recording with placement of intracranial
      electrodes could identify the seizure focus prior to surgery. This paper
      highlights the general information regarding the use of EEG in epilepsy, EEG
      patterns resembling epileptiform discharges, and the interictal, ictal and
      postictal findings in mesial temporal lobe epilepsy using scalp and intracranial
      recordings prior to surgery. The utility of the automated seizure detection and
      computerized mathematical models for increasing yield of non-invasive
      localization is discussed. This paper also describes the sensitivity,
      specificity, and predictive value of EEG for seizure recurrence after withdrawal
      of medications following seizure freedom with medical and surgical therapy.

PMID- 22957237
TI  - Role of functional MRI in presurgical evaluation of memory function in temporal
      lobe epilepsy.
AB  - Many diagnostic tools have been employed to predict the likelihood of a
      postoperative memory decline after a standard temporal lobectomy, including the
      intracarotid amobarbital testing (IAT) or Wada, regarded as the gold standard
      test for over the past half a century. Functional MRI (fMRI) is also a promising
      tool in that regard. Its routine use to predict the postoperative memory decline
      has been limited because of the varied study paradigms, discrepancies in
      analysis, and interpretation of the results. Based on the existing literatures,
      fMRI cannot replace IAT for the routine presurgical evaluation of the patients
      with temporal lobe epilepsy (TLE) yet. Large multicentre studies with a panel of
      memory test are required to determine the full potential of fMRI and use it
      reliably to replace IAT in the routine clinical practice. In this paper, we
      review various aspects of memory fMRI, including the experimental designs, data
      analysis, and findings.

PMID- 22957239
TI  - Noninvasive approach to focal cortical dysplasias: clinical, EEG, and
      neuroimaging features.
AB  - Purpose. The main purpose is to define more accurately the epileptogenic zone
      (EZ) with noninvasive methods in those patients with MRI diagnosis of focal
      cortical dysplasia (FCD) and epilepsy who are candidates of epilepsy surgery.
      Methods. Twenty patients were evaluated prospectively between 2007 and 2010 with
      comprehensive clinical evaluation, video-electroencephalography, diffusion tensor
      imaging (DTI), and high-resolution EEG to localize the equivalent current dipole
      (ECD). Key Findings. In 11 cases with white matter asymmetries in DTI the ECDs
      were located next to lesion on MRI with mean distance of 14.63 millimeters with
      topographical correlation with the EZ. Significance. We could establish a
      hypothesis of EZ based on Video-EEG, high-resolution EEG, ECD method, MRI, and
      DTI. These results are consistent with the hypothesis that the EZ in the FCD is
      complex and is often larger than visible lesion in MRI.

PMID- 22957238
TI  - Determining surgical candidacy in temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy that is
      amenable to surgical treatment. In the carefully selected patient, excellent
      seizure outcome can be achieved with minimal or no side effects from surgery.
      This may result in improved psychosocial functioning, achieving higher education,
      and maintaining or gaining employment. The objective of this paper is to discuss
      the surgical selection process of a patient with TLE. We define what constitutes
      a patient that has medically refractory TLE, describe the typical history and
      physical examination, and distinguish between mesial TLE and neocortical TLE. We
      then review the role of routine (ambulatory/sleep-deprived electroencephalography
      (EEG), video EEG, magnetic resonance imaging (MRI), neuropsychological testing,
      and Wada testing) and ancillary preoperative testing (positron emission
      tomography, single-photon emission computed tomography (SPECT), subtraction ictal
      SPECT correlated to MRI (SISCOM), magnetoencephalography, magnetic resonance
      spectroscopy, and functional MRI) in selecting surgical candidates. We describe
      the surgical options for resective epilepsy surgery in TLE and its commonly
      associated risks while highlighting some of the controversies. Lastly, we present
      teaching cases to illustrate the presurgical workup of patients with medically
      refractory TLE.

PMID- 22957240
TI  - Epileptic encephalopathy in children with risk factors for brain damage.
AB  - In the study of 887 new born infants with prenatal and perinatal risk factors for
      brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut
      syndrome and another 4 children with Lennox-Gastaut syndrome that had not been
      preceded by West syndrome were found. In this study we present the main findings
      of these 15 subjects. In all infants multifactor antecedents were detected. The
      most frequent risk factors were prematurity and severe asphyxia; however placenta
      disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI
      direct or secondary features of periventricular leukomalacia were observed.
      Followup of all infants showed moderate to severe neurodevelopmental delay as
      well as cerebral palsy. It is concluded that prenatal and perinatal risk factors
      for brain damage are very important antecedents that should be taken into account
      to follow up those infants from an early age in order to detect and treat as
      early as possible an epileptic encephalopathy.

PMID- 22957242
TI  - Microsurgical anatomy of the temporal lobe and its implications on temporal lobe
      epilepsy surgery.
AB  - Objective. We review the neuroanatomical aspects of the temporal lobe related to
      the temporal lobe epilepsy. The neuronal, the ventricular, and the vascular
      structures are demonstrated. Methods. The previous articles published from the
      laboratory of the senior author are reviewed. Results. The temporal lobe has four
      surfaces. The medial surface has a complicated microanatomy showing close
      relation to the intraventricular structures, such as the amygdala or the
      hippocampus. There are many white matter bundles in the temporal lobe showing
      relation to the extra- and intraventricular structures. The surgical approaches
      commonly performed to treat temporal lobe epilepsy are discussed under the light
      of these data. Conclusion. A thorough knowledge of the microanatomy is necessary
      in cortical, subcortical, and intraventricular structures of the temporal lobe to
      achieve better results.

PMID- 22957241
TI  - Temporal lobe epilepsy semiology.
AB  - Epilepsy represents a multifaceted group of disorders divided into two broad
      categories, partial and generalized, based on the seizure onset zone. The
      identification of the neuroanatomic site of seizure onset depends on delineation
      of seizure semiology by a careful history together with video-EEG, and a variety
      of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive
      intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of
      focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed
      surgically. A history of febrile seizures (especially complex febrile seizures)
      is common in TLE and is frequently associated with mesial temporal sclerosis (the
      commonest form of TLE). Seizure auras occur in many TLE patients and often
      exhibit features that are relatively specific for TLE but few are of lateralizing
      value. Automatisms, however, often have lateralizing significance. Careful study
      of seizure semiology remains invaluable in addressing the search for the seizure
      onset zone.

PMID- 22957243
TI  - Active epilepsy as indicator of neurocysticercosis in rural northwest India.
AB  - Objective. To determine the contribution of neurocysticercosis as a cause for
      active epilepsy and to establish Neurocysticercosis as major definable risk of
      epilepsy in our setup. Methods. We conducted a door-to-door survey of 2,209
      individuals of Bhore Pind and Bhore Kullian villages in Chattah zone of district
      Jammu (Jumma and Kashmir, Northwest India) to identify patients with symptomatic
      epilepsy. Patients with active epilepsy were investigated with neuroimaging
      techniques to establish diagnosis of NCC (neurocysticercosis). Results. Among 25
      patients with epilepsy 10(40%) had CT/MR evidence of past or recent NCC
      infection. This gave us the point prevalence of 4.5/1000 for Neurocysticercosis
      in our study population. Interpretation. The study shows a high prevalence of NCC
      accounting for symptomatic epilepsy in our part of India.

PMID- 22957245
TI  - Extrahippocampal desynchronization in nonlesional temporal lobe epilepsy.
AB  - Although temporal lobe epilepsy (TLE) is traditionally associated with both
      hypersynchronous activity in the form of interictal epileptic discharges and
      hippocampal sclerosis, recent findings suggest that desynchronization also plays
      a central role in the dynamics of this pathology. The objective of this work is
      to show the imbalance existing between mesial activities in patients suffering
      from mesial TLE, with normal mesial structures. Foramen ovale recordings from six
      patients with mesial TLE and one with lateral TLE were analyzed through a cluster
      analysis and synchronization matrices. None of the patients present findings in
      the MRI presurgical evaluation. Numerical analysis was carried out in three
      different situations: awake and sleep interictal and also during the preictal
      stage. High levels of desynchronization ipsilateral to the epileptic side were
      present in mesial TLE patients. Low levels of desynchronization were present in
      the lateral TLE patient during the interictal stage and almost zero in the
      preictal stage. Implications of these findings in relation with seizure spreading
      are discussed.

PMID- 22957244
TI  - Depression in temporal lobe epilepsy: a review of prevalence, clinical features,
      and management considerations.
AB  - Depression in temporal lobe epilepsy has been established as a frequent
      occurrence, and various possible mechanisms for this significant comorbidity have
      been posited. However, there is still little to guide a clinician in the
      recognition and management of depression in patients with temporal lobe epilepsy.
      This is in part due to the lack of consistent findings in earlier studies, which
      was likely partly due to variabilities in methodology, sampling, and diagnosis of
      both temporal lobe epilepsy and depression. However, in recent years, significant
      effort has been made to address these issues and provide a framework for
      diagnosis and management of depression in this population. The following is a
      review of the literature, with special emphasis on clinical phenomenology of
      depressive symptoms, described bidirectional risk between depression and temporal
      lobe epilepsy, and treatment strategies in the context of potential drug
      interactions with antiepileptic drugs.

PMID- 22957246
TI  - Language mapping in temporal lobe epilepsy in children: special considerations.
AB  - Temporal lobe epilepsy (TLE) in children is a slightly different entity than TLE
      in adults not only because of its semiology and pathology but also because of the
      different approach to surgical treatment. Presurgical investigations for eloquent
      cortex, especially language, must take these differences into account. Most
      diagnostic tests were created for adults, and many of the assessment tools need
      to be adapted for children because they are not just small adults. This paper
      will highlight the specific challenges and solutions in mapping language in a
      pediatric population with TLE.

PMID- 22957247
TI  - Temporal lobe epilepsy in children.
AB  - The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in
      infants and children differs from the relatively homogeneous syndrome seen in
      adults in several important clinical and pathological ways. Seizure semiology
      varies by age, and the ictal EEG pattern may be less clear cut than what is seen
      in adults. Additionally, the occurrence of intractable seizures in the developing
      brain may impact neurocognitive function remote from the temporal area. While
      many children will respond favorably to medical therapy, those with focal imaging
      abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade
      tumors are likely to be intractable. Expedient workup and surgical intervention
      in these medically intractable cases are needed to maximize long-term
      developmental outcome.

PMID- 22957248
TI  - Genetics of temporal lobe epilepsy: a review.
AB  - Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex
      disorder. To understand its genetic component, numerous linkage analyses of
      familial forms and association studies of cases versus controls have been
      conducted since the middle of the nineties. The present paper lists genetic
      findings for TLE from the initial segregation analysis to the most recent results
      published in May 2011. To date, no genes have been clearly related to TLE despite
      many efforts to do so. However, it is vital to continue replication studies and
      collaborative attempts to find significant results and thus determine which gene
      variant combination plays a definitive role in the aetiology of TLE.

PMID- 22957249
TI  - Neuropsychology in temporal lobe epilepsy: influences from cognitive neuroscience
      and functional neuroimaging.
AB  - Neuropsychologists assist in diagnosis (i.e., localization of dysfunction) and in
      prediction (i.e., how cognition may change following surgery) in individuals
      being considered for temporal lobe surgery. The current practice includes
      behavioural testing as well as mapping function via stimulation, inactivation,
      and (more recently) functional imaging. These methods have been providing
      valuable information in surgical planning for 60 years. Here, we discuss current
      assessment strategies and highlight how they are evolving, particularly with
      respect to integrating recent advances in cognitive neuroscience.

PMID- 22957250
TI  - Cognitive outcome of status epilepticus in children.
AB  - Epileptic encephalopathy encompasses conditions in which cognitive, motor, or
      sensory deficits result as a consequence of epileptic activity defining certain
      syndromes. It therefore represents a more severe subset of epilepsy, which can be
      generally characterized as frequent or severe seizures leading to cerebral
      dysfunction. This disturbance in cerebral functioning can in turn hinder,
      somewhat dramatically, cognitive development and further impact the future lives
      of patients. In this paper, we describe the cognitive consequences of status
      epilepticus in children and in adults in the context of plasticity theories.
      Recent studies maintain that consequences of SE may be severe cognitive sequelae,
      especially in early life. Since the residual consequences of SE in adulthood seem
      less detrimental and long-lasting, we argue that early life insults, such as
      those created by SE, during a rapid period of development and functional
      specialization, result in specific cognitive deficits dependent on the sensitive
      period at which SE occurred.

PMID- 22957251
TI  - Renal preservation therapy for renal cell carcinoma.
AB  - Renal preservation therapy has been a promising concept for the treatment of
      localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy
      (PN) is well accepted to treat the localized RCC and the oncological control is
      proved to be the same as the radical nephrectomy (RN). Under the result of well
      oncological control, minimal invasive method gains more popularity than the open
      PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic
      partial nephrectomy (RPN). On the other hand, thermoablative therapy and
      cryoablation also play an important role in the renal preservation therapy to
      improve the patient procedural tolerance. Novel modalities, but limited to small
      number of patients, include high-intensity ultrasound (HIFU), radiosurgery,
      microwave therapy (MWT), laser interstitial thermal therapy (LITT), and pulsed
      cavitational ultrasound (PCU). Although initial results are encouraging, their
      real clinical roles are still under evaluation. On the other hand, active
      surveillance (AS) has also been advocated by some for patients who are unfit for
      surgery. It is reasonable to choose the best therapeutic method among varieties
      of treatment modalities according to patients' age, physical status, and
      financial aid to maximize the treatment effect among cancer control, patient
      morbidity, and preservation of renal function.

PMID- 22957252
TI  - Osteoarthritis of the Wrist STT Joint and Radiocarpal Joint.
AB  - Our understanding of wrist osteoarthritis (OA) lags behind that of other joints,
      possibly due to the complexity of wrist biomechanics and the importance of
      ligamentous forces in the function of the wrist. Scaphotrapeziotrapezoidal (STT)
      OA is common, but its role in wrist clinical pathology and biomechanics is
      unclear. We identified the prevalence of radiographic STT joint OA in our hand
      clinic population and defined the relationship between STT and radiocarpal OA in
      wrist radiographs. One hundred consecutive wrist clinical and radiographic exams
      were retrospectively reviewed. Radiographs were evaluated for the presence and
      stage of OA. The mean age was 61.3 (+/-14.5) years. The radiographic occurrence
      of STT joint OA was 59% and of radiocarpal (RC) OA was 29%. Radiographic STT and
      RC joint OA were inversely related. Tenderness over the STT joint in physical
      exam was not associated with OA in the STT or other joints. STT OA in our series
      was not related to wrist pain. These findings support the discrepancy between
      radiographic and cadaver findings and clinically significant OA in this joint.
      The inverse relationship between STT and RC OA, as seen in scapholunate advanced
      collapse (SLAC) wrist, requires further biomechanical study.

PMID- 22957253
TI  - The Attitudes and Practices of General Practitioners about the Use of Chaperones
      in Melbourne, Australia.
AB  - Introduction. To consider the use of medical chaperones during certain clinical
      examinations is important whether one practises as a specialist, nurse, medical
      student, or generalist. Chaperones have been used by doctors conducting intimate
      examinations for many years but their true extent remains largely unknown. Until
      recently, there was no national guidance in Australia. Aim. To explore the
      attitudes and practices of general practitioners (GP) regarding their use of
      chaperones in urban Melbourne, Australia. Method. Qualitative two focus groups
      involving seventeen GPs from two locations. Discussions were audio-taped,
      transcribed verbatim and analysed. Results. Common themes and subthemes emerged
      which were grouped into three main areas: (a) practitioner-related, (b) patient
      related and (c) practice related. Discussion. This is the first study from an
      Australian primary care perspective to gauge the attitudes and experiences of GPs
      on their use of chaperones. It will provide vital information to inform the next
      step of extending this research to a national GP audience. From an international
      perspective, this study provides an excellent template for other primary care
      clinicians to conduct research in this important field of doctor-patient
      relationship.

PMID- 22957254
TI  - Proteinuria: from molecular to clinical applications in glomerulonephritis.

PMID- 22957255
TI  - Circulating adiponectin is associated with renal function independent of age and
      serum lipids in west africans.
AB  - Adiponectin, a protein secreted by adipose tissue, has been associated with renal
      dysfunction. However, these observations have not been adequately investigated in
      large epidemiological studies of healthy individuals in general and in African
      populations in particular. Hence, we designed this study to evaluate the
      relationship between adiponectin and renal function in a large group of
      nondiabetic West Africans. Total adiponectin was measured in 792 participants.
      MDRD and Cockroft-Gault (CG-) estimated GFR were used as indices of renal
      function. Linear and logistic regression models were used to determine the
      relationship between adiponectin and renal function. Adiponectin showed an
      inverse relationship with eGFR in univariate (Beta(MDRD) = -0.18, Beta(CG) = 
      0.26) and multivariate (Beta(MDRD) = -0.10, Beta(CG) = -0.09) regression
      analyses. The multivariate models that included age, sex, BMI, hypertension,
      smoking, HDL-C, LDL-C, triglycerides, and adiponectin explained 30% and 55.6% of
      the variance in GFR estimated by MDRD and CG methods, respectively. Adiponectin
      was also a strong predictor of moderate chronic kidney disease (defined as eGFR <
      60 mL/min/1.73 m(2)). We demonstrate that adiponectin is associated with renal
      function in nondiabetic West Africans. The observed relationship is independent
      of age and serum lipids. Our findings suggest that adiponectin may have clinical
      utility as a biomarker of renal function.

PMID- 22957256
TI  - The application of a three-step serum proteome analysis for the discovery and
      identification of novel biomarkers of hepatocellular carcinoma.
AB  - The representative tumor markers for HCC, AFP, and PIVKA-II are not satisfactory
      in terms of sensitivity and specificity in the early diagnosis of HCC. In search
      for novel markers for HCC, three-step proteome analyses were carried out in serum
      samples obtained from 12 patients with HCC and 10 with LC. As a first step, serum
      samples were subjected to antibody-based immunoaffinity column system that
      simultaneously removes twelve of abundant serum proteins. The concentrated flow
      through was then fractionated using reversed-phase HPLC. Proteins obtained in
      each fraction were separated by SDS-PAGE. Serum samples obtained from patient
      with HCC and with LC were analyzed in parallel and their protein expression
      patterns were compared. A total of 83 protein bands were found to be upregulated
      in HCC serum. All the protein bands, the intensity of which was different between
      HCC and LC groups, were identified. Among them, clusterin was most significantly
      overexpressed (P = 0.023). The overexpression of serum clusterin was confirmed by
      ELISA using another validation set of HCC samples. Furthermore, serum clusterin
      was elevated in 40% of HCC cases in which both AFP and PIVKA-II were within their
      cut-off values. These results suggested that clusterin is a potential novel serum
      marker for HCC.

PMID- 22957257
TI  - A novel Myosin essential light chain mutation causes hypertrophic cardiomyopathy
      with late onset and low expressivity.
AB  - Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding
      sarcomere proteins. Mutations in MYL3, encoding the essential light chain of
      myosin, are rare and have been associated with sudden death. Both recessive and
      dominant patterns of inheritance have been suggested. We studied a large family
      with a 38-year-old asymptomatic HCM-affected male referred because of a murmur.
      The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting
      left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm).
      Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in
      MYL3. The mutation was not found in 300 controls, and the patient had no
      mutations in 10 sarcomere genes. Cascade screening revealed a further nine
      heterozygote mutation carriers, three of whom had ECG and/or echocardiographic
      abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if
      we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%,
      but the mean age of the nonpenetrant mutation carriers is 15, while the mean age
      of the penetrant mutation carriers is 47. The mutation affects a conserved valine
      replacing it with a larger isoleucine residue in the region of contact between
      the light chain and the myosin lever arm. In conclusion, MYL3 mutations can
      present with low expressivity and late onset.

PMID- 22957258
TI  - Common carotid artery diameter and cardiovascular risk factors in overweight or
      obese postmenopausal women.
AB  - Arterial diameter is an underutilized indicator of vascular health. We
      hypothesized that interadventitial and lumen diameter of the common carotid
      artery would be better indicators of vascular health than carotid plaque or
      intima media thickness (IMT). Participants were 491 overweight or obese,
      postmenopausal women who were former or current hormone therapy (HT) users, 52-62
      years, with waist circumference >80 cm. We evaluated cross-sectional associations
      of cardiovascular risk factors with carotid measures, by HT status. Former HT
      users had a worse cardiovascular profile than current HT users: larger
      adventitial (6.94 mm versus 6.79 mm) and lumen diameter (5.44 mm versus 5.31 mm,
      both P < 0.01) independent of cardiovascular risk factors; IMT and plaque were
      similar. Larger diameters were best explained by former HT use, higher pulse
      pressure, and greater weight. Independent of potential confounders, overweight
      and obese postmenopausal former HT users had larger carotid diameters than
      current HT users. Carotid diameter should be considered in studies of HT.

PMID- 22957260
TI  - Milan Criteria and UCSF Criteria: A Preliminary Comparative Study of Liver
      Transplantation Outcomes in the United States.
AB  - The application of orthotopic liver transplantation (OLT) for patients with
      hepatocellular cancer (HCC) necessitates highly selective criteria to maximize
      survival and to optimize allocation of a scarce resource. The objective of this
      study was to compare the outcomes of OLT for HCC in patients transplanted under
      Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was
      queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972
      patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified.
      Patients were stratified by pretransplant criteria (Milan versus UCSF), and
      clinical and pathologic factors and overall survival were compared. There were no
      differences in age, gender, diabetes mellitus, body mass index, and hepatitis B,
      or C status between the two groups. Overall survival was similar between the
      Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and
      72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of
      patients within UCSF criteria was small, our results nevertheless suggest that
      patients with HCC may have equivalent survival when transplanted under Milan and
      UCSF criteria. Long-term followup may better determine whether UCSF criteria
      should be widely adopted.

PMID- 22957261
TI  - Computed Tomography Evaluation of Craniomandibular Articulation in Class II
      Division 1 Malocclusion and Class I Normal Occlusion Subjects in North Indian
      Population.
AB  - Objective. The purpose of this study is to investigate the Craniomandibular
      articulation morphology and position of condyle in mandibular fossae in Angle's
      class I normal occlusion and Angle's class II division 1 malocclusion. Materials
      and Methods. The present study was conducted on 40 subjects with 20 subjects in
      each group, and the computed tomography images were obtained using spiral
      computed tomography technique. Each measurement was compared by two-factor
      analysis of variance (ANOVA) while changes in anterior and posterior joint spaces
      were done by paired t-test. Results. Statistically significant anterior
      positioning of condyle (P > 0.05) was observed in class I normal malocclusion,
      and it was significant only on right side in class II division 1 malocclusion.
      Conclusions. There was no difference found in the condylar process and joint
      morphology between right and left sides of both Angle's Class I normal occlusion
      and Angle's class II division 1 malocclusion. Evaluation of the position of the
      condyles in their respective mandibular fossae showed concentric position with a
      tendency towards anterior positioning for both right and left sides of the
      subjects with Angle's Class I normal occlusion as well as subjects with Angle's
      class II division 1 malocclusion.

PMID- 22957259
TI  - Recent advances in pharmacotherapy development for abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a common disease causing segmental expansion
      and rupture of the aorta with a high mortality rate. The lack of nonsurgical
      treatment represents a large and unmet need in terms of pharmacotherapy. Advances
      in AAA research revealed that activation of inflammatory signaling pathways
      through proinflammatory mediators shifts the balance of extracellular matrix
      (ECM) metabolism toward tissue degradation. This idea is supported by
      experimental evidence in animal models that pharmacologic intervention at each
      pathological step can prevent AAA development. Previously, we identified c-Jun N
      terminal kinase (JNK), a pro-inflammatory signaling molecule, as a therapeutic
      target for AAA. Abnormal activation of JNK in AAA tissue regulates multiple
      pathological processes in a coordinated manner. Pharmacologic inhibition of JNK
      tips the ECM balance back towards repair rather than degradation. Interventions
      targeting signaling molecules such as JNK in order to manipulate multiple
      pathological processes may be an ideal therapeutic strategy for AAA. Furthermore,
      the development of biomarkers as well as appropriate drug delivery systems is
      essential to produce clinically practical pharmacotherapy for AAA.

PMID- 22957262
TI  - Compressive Strength and Setting Time of MTA and Portland Cement Associated with
      Different Radiopacifying Agents.
AB  - Objective. The aim of this study was to evaluate the compressive strength and
      setting time of MTA and Portland cement (PC) associated with bismuth oxide (BO),
      zirconium oxide (ZO), calcium tungstate (CT), and strontium carbonate (SC).
      Methods. For the compressive strength test, specimens were evaluated in an EMIC
      DL 2000 apparatus at 0.5 mm/min speed. For evaluation of setting time, each
      material was analyzed using Gilmore-type needles. The statistical analysis was
      performed with ANOVA and the Tukey tests, at 5% significance. Results. After 24
      hours, the highest values were found for PC and PC + ZO. At 21 days, PC + BO
      showed the lowest compressive strength among all the groups. The initial setting
      time was greater for PC. The final setting time was greater for PC and PC + CT,
      and MTA had the lowest among the evaluated materials (P < 0.05). Conclusion. The
      results showed that all radiopacifying agents tested may potentially be used in
      association with PC to replace BO.

PMID- 22957263
TI  - Trends in early outpatient drug therapy in pediatric inflammatory bowel disease
      in Finland: a nationwide register-based study in 1999-2009.
AB  - Objective. There are limited data on the changes of treatment strategies of
      disease-modifying drugs used to treat pediatric inflammatory bowel disease (IBD).
      Methods. We utilized data from two national registers: the Drug Reimbursement
      Register for drug costs (for identifying children with IBD) and the Drug Purchase
      Register (for exposure to drugs), both of which are maintained by the Social
      Insurance Institution of Finland. The frequencies and trends of drug therapy
      strategies during the first year of pediatric IBD were evaluated between 1999 and
      2009. Results. A total of 481 children diagnosed with IBD were identified. During
      the first six months, 68% of the patients purchased systemic corticosteroids;
      these combined with 5-aminosalicylic acid in almost all cases. The use of
      corticosteroids was stable from the early years compared with the end of the
      study period. In Crohn's disease, there was a trend towards more active use of
      azathioprine: the therapy was introduced earlier and proportion of pediatric
      patients purchasing azathioprine increased by up to 51% (P < 0.05). Conclusions.
      In pediatric IBD, the majority of patients purchased corticosteroid within the
      first six months, reflecting moderate-to-severe disease. During recent years in
      pediatric Crohn's disease, the therapeutic strategies of oral medication have
      changed towards more active immunosuppression with azathioprine.

PMID- 22957264
TI  - Symptoms and risk factors of ovarian cancer: a survey in primary care.
AB  - In spite of the increased awareness of ovarian cancer symptoms, the predictive
      value of symptoms remains very low. The aim of this paper is to obtain the views
      of general practitioners (GPs) in relation to symptom-based detection of ovarian
      cancer and to assess their knowledge for family history of breast and/or ovarian
      cancer as a predisposing factor for ovarian cancer. In this questionnaire survey,
      postal questionnaires were sent to 402 GPs in 132 primary care clinics, out of
      which we obtained 110 replies (27.4%). Approximately 26% of respondent GPs
      thought that the symptoms were more likely to be frequent, sudden, and
      persistent, and one-fifth were unsure of the importance of family history of
      breast cancer in relation to ovarian cancer. The participant GPs scored a set of
      symptoms for their relevance to ovarian cancer from 0 (not relevant) to 10 (most
      relevant). The highest scored symptoms were abdominal swelling (mean +/- SD, 8.19
      +/- 2.33), abdominal bloating (7.01 +/- 3.01), and pelvic pain (7.46 +/- 2.26).
      There was a relative lack of awareness for repetitive symptoms as well as
      gastrointestinal symptoms as an important feature in a symptom-based detection of
      ovarian cancer.

PMID- 22957265
TI  - Desires, Need, Perceptions, and Knowledge of Assisted Reproductive Technologies
      of HIV-Positive Women of Reproductive Age in Ontario, Canada.
AB  - The purpose of this cross-sectional study is to assess the desire, need,
      perceptions, and knowledge of assisted reproductive technologies (ARTs) for women
      living with HIV (WLWHIV) and determine correlates of ART knowledge desire. WLWHIV
      of reproductive age were surveyed using the survey instrument "The HIV Pregnancy
      Planning Questionnaire" at HIV/AIDS service organizations across Ontario, Canada.
      Of our cohort of 500 WLWHIV, median age was 38, 88% were previously pregnant, 78%
      desired more information regarding ART, 59% were open to the idea of receiving
      ART, 39% felt they could access a sperm bank, and 17% had difficulties conceiving
      (self-reported). Age, African ethnicity, and residence in an urban center were
      correlated with desire for more ART information. Of participants, 50% wanted to
      speak to an obstetrician/gynecologist regarding pregnancy planning, and 74%
      regarded physicians as a main source of fertility service information. While the
      majority of participants in our cohort desire access to ART information, most do
      not perceive these services as readily accessible. Healthcare practitioners were
      viewed as main sources of information regarding fertility services and need to
      provide accurate information regarding access. Fertility service professionals
      need to be aware of the increasing demand for ART among WLWHIV.

PMID- 22957266
TI  - Effectiveness of glycyrrhizinic Acid (glizigen) and an immunostimulant (viusid)
      to treat anogenital warts.
AB  - Genital warts are benign proliferations of skin and mucosa caused by the human
      papillomavirus infection (hereinafter referred to as HPV). It is one of the most
      common sexually transmitted diseases in the world, whose incidence rate has
      increased in the last three decades. Current treatment involves the physical
      destruction of the infected cells. The fact that there are many different types
      of treatment goes to show that none of them are uniformly effective or directly
      antiviral. Objective. Demonstrate the efficacy of Glizigen in the III-phase
      clinical trial combined with a food supplement (VIUSID) formulated to boost the
      immune system when treating external anogenital warts. Design. 100 patients
      clinically diagnosed with anogenital lesions were included in the trial and
      assigned to two groups of 50 individuals. Those from one group where treated with
      Glizigen and Viusid and those from the other group with 25% podophyllin in
      alcohol, the results from each were then compared. Results. The combined Glizigen
      Viusid treatment was seen to have an 87.5% efficacy rate, which was slightly more
      than that of the treatment with podophyllin, and there were hardly any adverse
      reactions reported during the treatment. Conclusions. the combined Glizigen
      Viusid treatment was effective in treating genital warts.

PMID- 22957267
TI  - Sociodemographic Predictors of Survival in Differentiated Thyroid Cancer: Results
      from the SEER Database.
AB  - Background. Differentiated thyroid carcinoma (DTC) is prognosticated upon a
      combination of tumor characteristics, such as histology and stage, and patient
      age. DTC is also notable for having a strong female predominance. Using a
      nationwide database with long follow-up times, we explored the interplay between
      tumor biology and patient characteristics in predicting mortality. Methods. The
      Surveillance, Epidemiology, and End Results (SEER) registry data 1973-2005 was
      examined for patients with DTC as their only known malignancy. Cox multivariate
      analyses were used to generate mortality hazard ratios to evaluate the effects of
      age, gender, ethnicity, and marital status. Results. We identified 55,995
      patients with DTC as their only malignancy. Consistent with the existing
      literature, the tumors are primarily diagnosed in women (77.5%), and
      predominantly affect Caucasians (78.3%). Female gender had a protective effect
      resulting in a 37% decrease in mortality. Age at diagnosis predicted mortality
      over age 40. Black ethnicity was associated with a 51% increase in mortality
      compared to Caucasians. Conclusion. Multiple demographic factors predict
      mortality in patients with DTC after adjusting for tumor characteristics, and
      they appear to have complex interactions. Recognizing the importance of these
      factors may enable clinicians to better tailor therapy.

PMID- 22957268
TI  - Oral metformin treatment prevents enhanced insulin demand and placental
      dysfunction in the pregnant rat fed a fructose-rich diet.
AB  - The intake of a fructose-rich diet (FRD) in the normal female rat induces
      features similar to those observed in the human metabolic syndrome phenotype. We
      studied the impact of FRD administration to mothers on pregnancy outcome. On
      gestational day (Gd) zero rats were assigned to either group: ad libitum drinking
      tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through
      pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were
      daily cotreated or not with metformin (60 mg/Kg/day oral; ND + MF and FRD + MF)
      and submitted to a high glucose load test on Gd 14. Additionally, placentas from
      different groups were studied on Gd 20. Data indicated that: (1) although FRD
      rats well tolerated glucose overload, their circulating levels of insulin were
      significantly higher than in ND rats; (2) the mesometrial triangle blood vessel
      area was significantly lower in placentas from FRD than ND dams; (3) the
      detrimental effects of FRD administration to mothers were ameliorated by
      metformin cotreatment. Our study suggests that excessive intake of fructose
      during pregnancy enhanced the risk for developing gestational diabetes and
      subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome
      induced by FRD.

PMID- 22957270
TI  - Menadione : sodium orthovanadate combination eliminates and inhibits migration of
      detached cancer cells.
AB  - Exposure of cancer cells to anticancer agents in cultures induces detachment of
      cells that are usually considered dead. These drug-induced detached cells (D
      IDCs) may represent a clinical problem for chemotherapy since they may survive
      anoikis, enter the circulation, invade other tissues and resume proliferation,
      creating a metastasis, especially in tissues where the bioavailability of
      anticancer agents is not enough to eliminate all cancer cells. In this study we
      evaluated the antiproliferative effect of menadione : sodium orthovanadate (M :
      SO) combination on A549 lung cancer cells as well as the ability of M : SO to
      induce cell detachment. In addition, we followed the fate and chemosensitivity of
      M : SO-induced detached cells. Using transwell chambers, we found that a fraction
      of the M : SO-induced detached cells were viable and, furthermore, were able to
      migrate, re-attach, and resume proliferation when re-incubated in drug-free
      media. The total elimination of A549 detachment-resistant cells and M : SO
      induced detached cells were successfully eliminated by equivalent M : SO
      concentration (17.5 MUM : 17.5 MUM). Thus, M : SO prevented cell migration.
      Similar results were obtained on DBTRG.05MG human glioma cells. Our data
      guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their
      implications for invasiveness and metastasis and their sensitivity to anticancer
      drugs.

PMID- 22957269
TI  - Short-Term Therapy with Rosiglitazone, a PPAR-gamma Agonist, Improves Metabolic
      Profile and Vascular Function in Nonobese Lean Wistar Rats.
AB  - A number of preclinical and clinical studies have reported blood-pressure
      lowering benefits of thiazolidinediones in diabetic subjects and animal models of
      diabetes. This study was designed to further elucidate vascular effects of
      rosiglitazone, on healthy nonobese, lean animals. Adult male Wistar rats were
      randomized and assigned to control and rosiglitazone-treated groups and were
      dosed daily with either vehicle or rosiglitazone (10 mg kg(-1) day(-1)) by oral
      gavage for 5 days. Compared with control group, rosiglitazone treatment
      significantly reduced plasma levels of triglycerides (>240%) and nonesterified
      free fatty acids (>268%) (both, P < 0.001). There were no changes in vascular
      contractility to KCl or noradrenaline between two groups. However, rosiglitazone
      therapy improved carbamylcholine-induced vasorelaxation (93 +/- 3 % versus
      control 78 +/- 2, P < 0.01) an effect which was abolished by L-NAME. There was no
      difference in sodium nitroprusside-induced vasorelaxation between the control and
      rosiglitazone-treated animals. These results indicate that short-term
      rosiglitazone therapy improves both metabolic profile and vascular function in
      lean rats. The vascular effect of rosiglitazone appears to be mediated by
      alteration in NO production possibly by activation of endothelial PPARgamma. This
      increased NO production together with improved lipid profile may explain
      mechanism(s) of blood-pressure-lowering effects of thiazolidinediones on both
      human and experimental animals.

PMID- 22957271
TI  - A method for ventricular late potentials detection using time-frequency
      representation and wavelet denoising.
AB  - This study proposes a method for ventricular late potentials (VLPs) detection
      using time-frequency representation and wavelet denoising in high-resolution
      electrocardiography (HRECG). The analysis is performed both with the signal
      averaged electrocardiography (SAECG) and in real time. A comparison between the
      temporal and the time-frequency analysis is also reported. In the first analysis
      the standard parameters QRSd, LAS40, and RMS40 were used; in the second
      normalized energy in time-frequency domain was calculated. The algorithm was
      tested adding artificial VLPs to real ECGs.

PMID- 22957273
TI  - Safe removal of the urethral catheter 2 days following laparoscopic radical
      prostatectomy.
AB  - Purpose. To assess the risks and benefits of early urethral catheter removal
      following laparoscopic radical prostatectomy. Materials and Methods. Between June
      2009 and April 2011, 114 patients underwent laparoscopic radical prostatectomy
      for clinically organ-confined prostate cancer. Candidates for early removal of
      the urethral catheter were selected intraoperatively on the basis of the
      integrity of the vesicourethral anastamosis and the ease of recatheterisation. In
      the selected cohort of patients, the urethral catheter was removed at day 2.
      Recatheterisation rates within this group were recorded and analysed. Results. Of
      the 114 patients who underwent laparoscopic prostatectomy, 64 (56%) were deemed
      suitable for removal of catheter on second postoperative day prior to discharge.
      The first 20 patients selected for early removal of urethral catheter were
      covered with a suprapubic catheter inserted at the time of surgery. Out of 64
      patients deemed suitable for early removal of urethral catheter, 53 (83%) were
      able to pass urine without complication. 11 patients (17%) developed urinary
      retention that necessitated recatheterisation. In all cases, reinsertion of
      catheter was performed easily and successfully without the need for cystoscopic
      guidance or adjuncts. Conclusions. Removal of the urethral catheter at day 2
      following laparoscopic prostatectomy is a safe procedure in carefully selected
      patients.

PMID- 22957274
TI  - Incidence and Surgical Importance of Zuckerkandl's Tubercle of the Thyroid and
      Its Relations with Recurrent Laryngeal Nerve.
AB  - Background. Variations of recurrent laryngeal nerve (RLN) and Zuckerkandl's
      tubercle (ZT), which is posterior extension of lateral lobes, may affect safety
      of thyroidectomy. Methods. Total and hemithyroidectomy were surgical procedures
      in 60 and 40 patients, respectively. Surgical anatomy was studied in 87 right and
      73 left lobes. Presence of ZT was noted and its incidence was determined. RLNs
      were identified and fully isolated. Relationship between ZT and RLN was
      established. Results. ZTs were identified in 66 (66%) patients and in 81 (51%)
      lobes. ZT was present in 53 (61%) right and in 28 (38%) left lobes. ZTs were
      bilateral in 15 (25%) of 60 total thyroidectomy cases. Smaller tubercles show the
      neurovascular crossing point. RLN was posterior (medial) to ZT in 76 (94%)
      occurrences. RLN was laying on anterior surface of ZT only in 5 (6%) instances.
      Conclusions. RLN is unusually laying lateral to ZT which is common structure in
      the thyroid. Lateral RLN may be more vulnerable to injury. Total thyroidectomy
      requires dissection of ZT adjacent to RLN. Based on unusual relations and
      variations, RLN should be fully isolated before excision of adjacent structures.

PMID- 22957275
TI  - To Sleeve or NOT to Sleeve in Bariatric Surgery?
AB  - Morbid obesity has become a global epidemic during the 20th century. Until now
      bariatric surgery is the only effective treatment for this disease leading to
      sustained weight loss and improvement of comorbidities. The sleeve gastrectomy is
      becoming a promising alternative for the gold standard the gastric bypass and it
      is gaining popularity as a stand-alone procedure. The effect of the laparoscopic
      sleeve gastrectomy is based on a restrictive mechanism, but a hormonal effect
      also seems to play an important role. Similar results are achieved in terms of
      excess weight loss and resolution of comorbidities compared to the gastric
      bypass. Inadequate weight loss or weight regain can be treated by revisional
      surgery. Complication rates after LSG appear to be lower compared with gastric
      bypass. General guidelines recommend bariatric surgery between the age of 18 and
      65. However bariatric surgery in the elderly seems safe with respect to weight
      loss and resolution of comorbidities. At the same time weight loss surgery is
      more often performed in adolescent patients failing weight loss attempts. Even
      though more studies are needed describing long-term effects, there is already
      enough evidence that this technique is an effective single procedure for a
      considerable proportion of obese patients.

PMID- 22957272
TI  - Primary prevention of heart failure.
AB  - Most heart failure research and quality improvement efforts are targeted at
      treatment and secondary prevention of patients with manifest heart failure. This
      is distinct from coronary disease where primary prevention has been a focus for
      over three decades. Given the current importance and the projected worsening of
      heart failure epidemiology, a more focused effort on prevention is urgently
      needed.

PMID- 22957276
TI  - The role of the immune system in nevirapine-induced subclinical liver injury of a
      rat model.
AB  - In this study, the role of the immune system in nevirapine- (NVP-) induced
      subclinical liver injury was investigated by observing for changes of some immune
      parameters during the initial stages of NVP-induced hepatotoxicity in a rat
      model. In the acute phase, two test-groups of 10 Sprague-Dawley rats each were
      administered with bacterial lipopolysaccharide (LPS) or saline (S)
      intraperitoneally, followed by oral NVP, after which 5 rats from each group were
      sacrificed at 6 and 24 hours. For the chronic phase, two groups of 15 rats each
      received daily NVP, and on days 7, 14, and 21, five rats from each group were
      administered with either LPS or S, followed by that day's NVP dose, and were
      sacrificed 24 hours later. NVP caused liver injury up to seven days and
      progressively increased IL-2 and IFN-gamma levels and lymphocyte count over the
      21 days. NVP-induced liver injury was characterized by apoptosis and degeneration
      changes, while, for LPS, it was cell swelling, leukostasis, and portal
      inflammation. Coadministration of NVP and LPS attenuated NVP-induced liver
      injury. In conclusion, the immune system is involved in NVP toxicity, and the LPS
      effects may lay the clue to development of therapeutic strategies against NVP
      induced hepatotoxicity.

PMID- 22957277
TI  - A Case of Horner's Syndrome following Ultrasound-Guided Infraclavicular Brachial
      Plexus Block.
AB  - Horner's syndrome results from paralysis of the ipsilateral sympathetic cervical
      chain (stellate ganglion) caused by surgery, drugs (mainly high concentrations of
      local anesthetics), local compression (hematoma or tumor), or inadequate
      perioperative positioning of the patient. It occurs in 100% of the patients with
      an interscalene block of the brachial plexus and can also occur in patients with
      other types of supraclavicular blocks.In this case report, we presented a case of
      Horner's syndrome after performing an ultrasound-guided infraclavicular brachial
      plexus block with 15 mL of bupivacaine 0.5%. It appeared 40 minutes after the
      block with specific triad (ptosis, miosis, and exophtalmia) and quickly
      disappears within 2 hours and a half without any sequelae. Horner's syndrome may
      be described as an unpleasant side effect because it has no clinical consequences
      in itself. For this reason anesthesiologists should be aware of this syndrome,
      and if it occurs patients should be reassured and monitored closely.

PMID- 22957278
TI  - Idiopathic peripheral neuropathy responsive to sympathetic nerve blockade and
      oral clonidine.
AB  - A 52-year-old female presented with idiopathic stocking-glove neuropathy. She
      underwent a series of right and left stellate ganglion blocks with ropivacaine
      and clonidine, followed by lumbar sympathetic blocks. This resulted in complete
      symptom relief for two weeks. These procedures were repeated after a two-month
      interval; at that time she was still experiencing partial relief from the first
      series. She again remained completely pain free for several weeks following the
      injections. As the pain partially returned, daily oral clonidine was initiated
      and resulted in almost complete cessation of her symptoms, which persisted at a
      three-month follow-up examination.

PMID- 22957279
TI  - Foldable denture: for microstomia patient.
AB  - Microstomia may result from surgical treatment of orofacial neoplasms, cleft
      lips, maxillofacial trauma, burns, radiotherapy, or scleroderma. A maximal oral
      opening that is smaller than the size of a complete denture can make prosthetic
      treatment challenging. This clinical paper presents the prosthodontic management
      of a total edentulous patient with microstomia. Sectional mandibular and
      maxillary trays and foldable mandibular and maxillary denture were fabricated for
      the total edentulous patient.

PMID- 22957280
TI  - Early pathologic findings of bronchiolitis obliterans after allogeneic
      hematopoietic stem cell transplantation: a proposal from a case.
AB  - Bronchiolitis obliterans (BO) is one of the serious, noninfectious pulmonary
      complications after allogeneic hematopoietic stem cell transplantation (allo
      HSCT). Early diagnosis of BO is usually difficult because patients are often
      asymptomatic at an initial stage of the disease and pathologic findings are
      available mostly at the late stages. Therefore, the diagnosis of the disease is
      based on the pulmonary function test using the National Institute of Health
      consensus criteria. Here, we report a case of slowly progressive BO. A biopsy
      specimen at an early stage demonstrated alveolar destruction with lymphocyte
      infiltration in bronchial walls and mild narrowing of bronchioles without
      fibrosis, those were strongly indicative of initial pathologic changes of BO.
      Definitive BO followed, which was proven by both clinical course and autopsy.
      While alloreactive lymphocytes associated with chronic graft-versus-host disease
      are believed to initiate BO, we present a rare case that directly implies such a
      scenario.

PMID- 22957281
TI  - Prenatal diagnosis of congenital syphilis using two- and three-dimensional
      ultrasonography: case report.
AB  - The numbers of syphilis cases have been increasing considerably, especially in
      eastern europe, thereby contributing towards greater chances of cases of
      congenital syphilis. Some of the complications of congenital syphilis can be
      detected on two-dimensional ultrasonography (2DUS), and these are generally
      manifested in the second trimester of pregnancy. The commonest ultrasonographic
      signs are hepatosplenomegaly, placentomegaly, and fetal growth restriction, while
      lower-frequency occurrences include intrahepatic calcifications, ascites, fetal
      hydrops, and even fetal death. Three-dimensional ultrasonography (3DUS) is a
      relatively new imaging technique that is adjuvant to 2DUS and enables detailed
      assessment of the fetal surface anatomy. We present a case of a 21-year-old
      primigravida with a diagnosis of congenital syphilis, with obstetric 2DUS
      findings of hepatosplenomegaly, ascites, pericardial effusion and
      hyperechogenicity of the cerebral parenchyma. 3DUS in rendering mode allowed
      clear assessment of the fetal limbs, especially the feet, which appeared twisted
      and lacked some toes. It allowed the parents to understand the pathological
      condition better and improved prenatal management and neonatal followup. 3DUS can
      be used routinely for assessing fetal malformations resulting from congenital
      infections.

PMID- 22957282
TI  - A mysterious gram-positive rods.
AB  - We encountered a patient with a history of intravenous drug use presenting with
      fever, malaise and nausea who was found to have cavitary lung lesions.
      Unexpectedly, gram positive rods grew out on day five on multiple blood cultures,
      which were later identified as Mycobacterium fortuitum. The patient underwent
      transesophageal echocardiogram, which showed aortic and tricuspid valve
      vegetations. Liver biopsy demonstrated granulomatous hepatitis. Interestingly,
      serum alkaline phosphatase level fell with antibiotic treatment. Mycobacterium
      fortuitum is ubiquitous worldwide, being found in tap water, and soil. M.
      fortuitum is usually considered as a contaminant. Disseminated infection caused
      by this bacterium in an immunocompetent host is extremely rare. Most of the
      disseminated infections have been reported in immune-deficient patients. In
      immunocompetent people, M. fortuitum causes human infection primarily by direct
      inoculation, including localized post-traumatic and surgical wound infections,
      and catheter-related sepsis. Our patient, an HIV-negative intravenous drug user,
      had Mycobacterium fortuitum sepsis associated with infective endocarditis, septic
      pulmonary emboli, and granulomatous hepatitis. Interestingly, the patient
      admitted using tap water occasionally for mixing heroin when her sterile water
      ran out, which we thought was the likely source of M. fortuitum.

PMID- 22957283
TI  - Comparison of Sexual Dysfunction Using the Female Sexual Function Index following
      Surgical Treatments for Uterine Fibroids.
AB  - Uterine fibroids are a common problem in women. Statistics showing 20-50% of
      fibroids produce symptoms and consequently patients seek surgical intervention to
      improve their quality of life. Treatments for fibroids are typically successful
      in controlling the fibroid disease, yet sexual function following invasive
      surgical treatments for fibroids can be jeopardized. The Sexual Function Index
      (FSFI) is a valid instrument producing quantifiable reproducible results. In this
      paper three case reports are evaluated by the FSFI and compared between the
      following treatment groups: hysterectomy, myomectomy, and uterine embolization.
      Our goal is to illustrate how each of these treatment outcomes can result in
      sexual dysfunction and therefore decreased quality of life. Effects of invasive
      fibroid treatments on sexual functioning would be helpful in guiding patient's
      ultimate decisions regarding treatment.

PMID- 22957284
TI  - A case of angiomyolipoma rarely located in the larynx.
AB  - Angiomyolipoma is a rare benign mesenchymal tumor, which is mostly renal in
      origin. A sixty-year-old male patient with the diagnosis of angiomyolipoma
      located in the larynx has been presented here, and the literature is reviewed.

PMID- 22957285
TI  - Myoepithelial cell-rich pleormorphic adenoma of minor salivary gland of
      parapharyngeal space.
AB  - Parapharyngeal space tumors are rare and constitute only 0.5-1.0% of head and
      neck tumors. Minor salivary gland tumor is still rare in parapharyngeal space. We
      are reporting a case of pleomorphic adenoma of minor salivary gland of
      parapharyngeal space. A 42-year-old female presented with a history of mass in
      the oropharynx for 3 years. She presented with "hot potato voice" and dysphagia.
      CECT and MRI were done, showing large parapharyngeal space tumor. FNAC was
      suspicious for tumor of nerve cell origin. Tumor was excised using "paramedian
      mandibulotomy with mandibular swing approach". Histopathological examination was
      inconclusive, suggesting possibility of extraskeletal myxoid chondrosarcoma,
      solitary fibrous tumor, neurogenic tumor. On immunohistochemistry, tumor was
      positive for cytokeratin, EMA (dim), S-100, and P 63 and negative for SMA thus
      proving the case as myoepithelial cell-rich pleomorphic adenoma.

PMID- 22957286
TI  - Autopsy findings in conjoined twin with single heart and single liver.
AB  - Thoracoomphalopagus is the commonest type of conjoined twin where the bodies are
      fused from upper chest to lower chest. The autopsy done can help counsil the
      parents for further pregnancies and determine the prognosis depending upon the
      type of cardiac anomaly by Seo classification when detected antenatally. We
      describe the detail pathological autopsy of such a case with single heart and
      single liver. A detail autopsy was done on the twin fetus. The twins shared a
      single heart and sometimes the liver and part of digestive system. The combined
      weight was 4.1 KG. Both were full-term male babies joined from below the nipple
      till umbilicus. Autopsy in conjoined twins helps in deciding the type of fusion
      of the body and also of the heart and great vessels. It can help in counseling
      parents about future pregnancies that there is no chance of recurrence of this
      abnormality and no need to be scared.

PMID- 22957287
TI  - Malignant perivascular epithelioid cell tumor of the esophagus.
AB  - Malignant perivascular epithelioid cell tumor (PEComa) is a rare tumor composed
      of hybrid tumor cells characterized by immunoreactivity for both melanocytic and
      smooth muscle markers. This paper describes the uncommon esophageal location of
      an 8 cm PEComa in a 75-year-old Caucasian man who was presented with ingravescent
      dysphagia. Although PEComas arising within the gastrointestinal tract are
      exceptional findings, clinicians should not exclude this class of tumors in the
      diagnostic investigation of a bulky lesion of the esophageal wall.

PMID- 22957288
TI  - Amyloid beta-Related Angiitis Causing Coma Responsive to Immunosuppression.
AB  - Introduction. Amyloid-beta-related angiitis (ABRA) is a form of CNS vasculitis in
      which perivascular beta-amyloid in the intracerebral vessels is thought to act as
      a trigger for inflammation mediated by CD68+ macrophages and CD3+ T lymphocytes.
      Patients with severe ABRA may develop coma responsive to immunosuppressive
      treatment. Case Presentation. A 57-year-old man presented to the neurological
      intensive care unit febrile, obtunded, and with a left hemiparesis. He had
      suffered from intermittent left arm weakness and numbness for several months
      prior. Serum and cerebrospinal fluid studies showed a lymphocytic leukocytosis in
      the cerebrospinal fluid (CSF), but no other evidence of infection, and the
      patient underwent a brain biopsy. Histopathological examination demonstrated
      amyloid angiopathy, with an extensive perivascular lymphocytic infiltrate,
      indicative of ABRA. The patient was started on cyclophosphamide and steroids.
      Following a week of treatment he awakened and over several weeks made a
      significant neurological recovery. Conclusions. ABRA can have a variety of
      clinical presentations, including impairments in consciousness and coma. Accurate
      pathological diagnosis, followed by aggressive immunosuppression, can lead to
      impressive neurological improvements. This diagnosis should be considered in
      patients with paroxysmal recurrent neurological symptoms and an accelerated
      progression.

PMID- 22957289
TI  - Necrotizing sialometaplasia of palate: a case report.
AB  - Background. Necrotizing sialometaplasia (NS) is an uncommon benign reactive
      necrotizing inflammatory process involving minor salivary gland that often mimics
      malignancy both clinically and histopathologically. Case Report. We report the
      case of a healthy 26-year-old man with a painless swelling in the hard palate
      near the middle raphe, asymptomatic, well limited, and raised edges. The patient
      was submitted to incisional biopsy and histopathological examination. The
      histological diagnosis was necrotizing sialometaplasia. Discussion. The clinical
      and histological similarity between this entity and a malignant lesion implies a
      risk of unnecessary or mistreatment. Therefore, clinicians and pathologists
      should be aware of this lesion as to avoid errors in the diagnosis and treatment
      of this benign pathologic condition.

PMID- 22957290
TI  - Severe gastrooesophageal reflux disease associated with foetal alcohol syndrome.
AB  - Prenatal alcohol exposure may have adverse effects on the developing foetus
      resulting in significant growth restriction, characteristic craniofacial
      features, and central nervous system dysfunction. The toxic effects of alcohol on
      the developing brain are well recognised. However, little is known about the
      effects of alcohol on the developing gastrointestinal tract or their mechanism.
      There are few case reports showing an association between foetal alcohol syndrome
      and gastrointestinal neuropathy. We report a rare association between foetal
      alcohol syndrome and severe gastrooesophageal reflux disease in an infant who
      ultimately required fundoplication to optimise her growth and nutrition. The
      child had failed to respond to maximal medical treatment (domperidone and
      omeprazole), high calorie feeds, PEG feeding, or total parenteral nutrition. The
      effect of alcohol on the developing foetus is not limited to the central nervous
      system but also can have varied and devastating effects on the gastrointestinal
      tract.

PMID- 22957291
TI  - EGFR-Mutant Lung Adenocarcinoma Mimicking a Pneumonia.
AB  - PET-CT scan has demonstrated to be very effective in lung cancer diagnosis and
      staging, but lung cancer has multiple ways of presentation, which can lead to an
      error in diagnosis imaging and a delay on the beginning of specific treatment. We
      present a case of a 77-year-old man with an initial PET-CT scan showing high 18F
      FDG intake, suggesting a bilateral pneumonia, who was finally diagnosed of an
      EGFR-mutant lung adenocarcinoma. EGFR-activating mutation allowed us to start
      treatment with the oral tyrosin kinase inhibitor Gefitinib, obtaining a rapid and
      sustained response. Histological confirmation of imaging findings is always
      necessary to avoid diagnostic errors.

PMID- 22957292
TI  - Acute fibrinous and organizing pneumonia and undifferentiated connective tissue
      disease: a case report.
AB  - Acute fibrinous and organizing pneumonia (AFOP), recently described, is a
      histologic pattern characterized by the presence of fibrin "balls" within
      alveolar spaces. The term undifferentiated connective tissue disease (UCTD) is
      used to identify autoimmune systemic diseases that do not fulfill the criteria to
      be classified as a definitive connective tissue disease. The AFOP has never been
      reported in association with UCTD. The present reported case is a 39-year-old
      Caucasian, female with dry cough and progressive dyspnea. Eight months later, she
      was diagnosed with "organizing pneumonia" based on clinical history and
      radiologic images. She manifested Raynaud's Phenomenon, sicca syndrome, boot and
      gloves neuropathic pain, and previous hypothyroidism. Antinuclear antibody,
      rheumatoid factor, and specific autoantibodies were negative. Salivary gland
      biopsy and electroneuromyiography were normal. The capillaroscopy showed a
      "scleroderma" pattern with capillary deletion and ectasia. She experienced
      clinical and radiologic worsening. Despite being submitted to cyclophosphamide
      pulse, she developed hemorrhage and then died. Thoracotomy pulmonary specimen
      showed histological pattern of AFOP. This paper shows a rare association of AFOP
      with UCTD.

PMID- 22957294
TI  - Intraabdominal compartment syndrome complicating transurethral resection of
      bladder tumor.
AB  - Abdominal compartment syndrome can result from many different causes. We present
      a case where this dangerous syndrome occurred in the operating room during a
      transurethral resection of a bladder tumor. It was initially recognized by an
      elevation in the peak inspiratory pressure. We report the typical physiologic
      changes that occur with this syndrome and its treatment options.

PMID- 22957293
TI  - Inferior Lateral Genicular Artery Injury during Anterior Cruciate Ligament
      Reconstruction Surgery.
AB  - We report a case of inferior lateral genicular artery (ILG) injury during
      anterior cruciate ligament (ACL) reconstruction surgery with lateral partial
      meniscectomy. This is a rare arthroscopy complication. A review of the literature
      has been made with the aim to define the anatomy of ILG across the lateral
      articular line and the risk of lesion during knee arthroscopy. We propose
      embolization as a good treatment option for this type of injuries.

PMID- 22957295
TI  - Hemodynamic monitoring.

PMID- 22957296
TI  - Gender differences in the influence of social support on one-year changes in
      functional status in older patients with heart failure.
AB  - The purpose of this study was to determine the combined effects of gender and
      levels of social support on 1-year functional health outcomes in older persons
      diagnosed with heart failure (HF). Persons >= 65 years of age with an acute HF
      exacerbation (164 females; 271 males) were enrolled and followed for a year.
      Participants completed baseline and 12-month questionnaires containing clinical
      and demographic descriptive information and validated self-report measures of:
      (1) physical functioning (Medical Outcome Study [MOS] SF12 and Kansas City
      Cardiomyopathy Questionnaire [KCCQ]) and (2) social support (MOS- Social Support
      Survey). Women were more likely to be single, widowed or divorced, living alone
      and earning less annual income. At baseline, women reported significantly lower
      support and physical function scores. However, at 1 year there were no
      significant gender differences in the proportion of men or women who experienced
      clinically meaningful functional decline or death across the year of follow-up.
      In multivariable modeling, men with lower levels of social support were more
      likely to experience functional decline. This was not the case for women. Our
      findings suggest that gender-directed strategies to promote optimization of
      function for both men and women living with HF in their community are warranted.

PMID- 22957297
TI  - Reliable Measurements of the beta-Amyloid Pool in Blood Could Help in the Early
      Diagnosis of AD.
AB  - The present study was aimed at assessing the capability of Abeta1-40 and Abeta1
      42 levels in undiluted plasma (UP), diluted plasma (DP), and cell bound (CB) to
      distinguish between early stages of Alzheimer's disease (AD), amnesic mild
      cognitive impairment (MCI), and healthy control (HC). Four blood samples from
      each participant were collected during one month and the levels of Abeta1-40 and
      Abeta1-42 were determined by a blinded proprietary ELISA sandwich (Araclon
      Biotech. Zaragoza, Spain). First striking result was that the amount of Abeta1-40
      and Abeta1-42 in UP represented only a small proportion (~15%) of the total beta
      amyloid pool in blood (betaAPB) described here as the sum of Abeta1-40 and Abeta1
      42 in blood where they are free in plasma, bound to plasma proteins, and bound to
      blood cells. Furthermore, we found that levels of Abeta1-40 and Abeta1-42 in UP,
      DP, and CB were significantly higher in MCI when compared to HC. On average, the
      total betaAPB was 1.8 times higher in MCI than in HC (P = 0.03) and allowed to
      discriminate between MCI and HC with a sensitivity and specificity over 80%.
      Thus, quantification of several markers of the betaAPB could be useful and
      reliable in the discrimination between MCI and HC.

PMID- 22957300
TI  - Evolutionary mechanisms of microbial genomes 2012.

PMID- 22957298
TI  - Microglia, Alzheimer's disease, and complement.
AB  - Microglia, the immune cell of the brain, are implicated in cascades leading to
      neuronal loss and cognitive decline in Alzheimer's disease (AD). Recent genome
      wide association studies have indicated a number of risk factors for the
      development of late-onset AD. Two of these risk factors are an altered immune
      response and polymorphisms in complement receptor 1. In view of these findings,
      we discuss how complement signalling in the AD brain and microglial responses in
      AD intersect. Dysregulation of the complement cascade, either by changes in
      receptor expression, enhanced activation of different complement pathways or
      imbalances between complement factor production and complement cascade inhibitors
      may all contribute to the involvement of complement in AD. Altered complement
      signalling may reduce the ability of microglia to phagocytose apoptotic cells and
      clear amyloid beta peptides, modulate the expression by microglia of complement
      components and receptors, promote complement factor production by plaque
      associated cytokines derived from activated microglia and astrocytes, and disrupt
      complement inhibitor production. The evidence presented here indicates that
      microglia in AD are influenced by complement factors to adopt protective or
      harmful phenotypes and the challenge ahead lies in understanding how this can be
      manipulated to therapeutic advantage to treat late onset AD.

PMID- 22957299
TI  - The genetic basis of female mate preference and species isolation in Drosophila.
AB  - The processes that underlie mate choice have long fascinated biologists. With the
      advent of increasingly refined genetic tools, we are now beginning to understand
      the genetic basis of how males and females discriminate among potential mates.
      One aspect of mate discrimination of particular interest is that which isolates
      one species from another. As behavioral isolation is thought to be the first step
      in speciation, and females are choosy more often than males in this regard,
      identifying the genetic variants that influence interspecies female mate choice
      can enhance our understanding of the process of speciation. Here, we review the
      literature on female mate choice in the most widely used model system for studies
      of species isolation Drosophila. Although females appear to use the same traits
      for both within- and between-species female mate choice, there seems to be a
      different genetic basis underlying these choices. Interestingly, most genomic
      regions that cause females to reject heterospecific males fall within areas of
      low recombination. Likely, candidate genes are those that act within the auditory
      or olfactory system, or within areas of the brain that process these systems.

PMID- 22957301
TI  - Positive Selection and the Evolution of izumo Genes in Mammals.
AB  - Most genes linked to male reproductive function have been known to evolve rapidly
      among species and to show signatures of positive selection. Different male
      species-specific reproductive strategies have been proposed to underlie positive
      selection, such as sperm competitive advantage and control over females
      postmating physiology. However, an underexplored aspect potentially affecting
      male reproductive gene evolution in mammals is the effect of gene duplications.
      Here we analyze the molecular evolution of members of the izumo gene family in
      mammals, a family of four genes mostly expressed in the sperm with known and
      potential roles in sperm-egg fusion. We confirm a previously reported bout of
      selection for izumo1 and establish that the bout of selection is restricted to
      the diversification of species of the superorder Laurasiatheria. None of the
      izumo genes showed evidence of positive selection in Glires (Rodentia and
      Lagomorpha), and in the case of the non-testes-specific izumo4, rapid evolution
      was driven by relaxed selection. We detected evidence of positive selection for
      izumo3 among Primates. Interestingly, positively selected sites include several
      serine residues suggesting modifications in protein function and/or localization
      among Primates. Our results suggest that positive selection is driven by aspects
      related to species-specific adaptations to fertilization rather than sexual
      selection.

PMID- 22957302
TI  - PAR6B is required for tight junction formation and activated PKCzeta localization
      in breast cancer.
AB  - Dysregulation of mechanisms that govern the control of epithelial cell polarity,
      morphology and plasticity are emerging as key processes in tumor progression. In
      this study we report amplification and overexpression of PAR6B, an essential
      component in epithelial cell tight junction (TJ) formation and maintenance of
      apico-basal polarity, in breast cancer cell lines. Analysis of chromosome
      20q13.13 in 11 breast cancer cell lines by fluorescence in situ hybridization
      (FISH) identified a novel small amplicon centered at PARD6B in 5 cell lines, with
      copy number ranging from 7 to 27. The presence of the PARD6B amplicon correlated
      with PARD6B transcript and PAR6B protein abundance. Expression of related
      isoforms PARD6A and PARD6G were detectable at significantly lower levels. PARD6B
      overexpression correlated with TJ network formation in cultured cell monolayers.
      SiRNA-mediated inhibition of PAR6B in MCF7 resulted in loss of TJ assembly and
      membrane localization of atypical PKCzeta (aPKC), but did not affect adherens
      junction formation. SiRNA-mediated inhibition of CDC42 in MCF7 also resulted in
      loss of TJ networks, confirming the requirement of a complete PAR6-aPKC-CDC42
      PAR3 complex to activate and stabilize TJs. Immunohistochemical analysis of PAR6B
      expression on breast tumor microarrays indicated exquisite epithelial cell
      specificity. Few quantitative differences in staining were observed between
      normal epithelium and adjacent tumor margins. However staining appeared reduced
      and cytoplasmic in more poorly differentiated tumors. We propose that
      quantitative imbalances in the components of pathways governing normal epithelial
      cell polarity arising from gain or loss of function may radically alter
      epithelial cell architecture and contribute to tumor progression.

PMID- 22957303
TI  - High levels of Hdmx promote cell growth in a subset of uveal melanomas.
AB  - The p53 tumor suppressor pathway is inactivated in cancer either via direct
      mutation or via deregulation of upstream regulators or downstream effectors. P53
      mutations are rare in uveal melanoma. Here we investigated the role of the p53
      inhibitor Hdmx in uveal melanoma. We found Hdmx over-expression in a subset of
      uveal melanoma cell lines and fresh-frozen tumor samples. Hdmx depletion resulted
      in cell-line dependent growth inhibition, apparently correlating with
      differential Hdm2 levels. Surprisingly, p53 knockdown hardly rescued cell cycle
      arrest and apoptosis induction upon Hdmx knockdown, whereas it effectively
      prevented growth suppression induced by the potent p53 activator Nutlin-3. In
      addition, two compounds inhibiting Hdmx function or expression, SAH-p53-8 and XI
      011, also elicited a growth inhibitory effect in a partly p53-independent manner.
      These findings suggest a novel, growth-promoting function of Hdmx that does not
      rely on its ability to inhibit p53. We provide evidence for a contribution of p27
      protein induction to the observed p53-independent G1 arrest in response to Hdmx
      knockdown. In conclusion, our study establishes the importance of Hdmx as an
      oncogene in a subset of uveal melanomas and widens the spectrum of its function
      beyond p53 inhibition.

PMID- 22957305
TI  - Regulation of cancer stem cell activities by tumor-associated macrophages.
AB  - Recent studies revealed that tumor-associated macrophages play a decisive role in
      the regulation of tumor progression by manipulating tumor oncogenesis,
      angiogenesis and immune functions within tumor microenvironments. However, the
      role of cancer stem cells in the tumorigenic activities of tumor-associated
      macrophages during the course of transformation and treatment remains largely
      unknown. Recent studies have clarified the functional aspects of tumor-associated
      macrophages in the regulation of the tumorigenic activities and anticancer drug
      responsiveness of cancer stem cells through complex networks formed by distinct
      sets of cytokines, chemokines and growth factors. In this article we discuss
      recent advances and future perspectives regarding the molecular interplay between
      cancer stem cells and tumor-associated macrophages and provide future perspective
      about the therapeutic implication against treatment-resistant variants of cancer.

PMID- 22957304
TI  - Cell cycle control in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the result of a multistep transforming process of
      hematopoietic precursor cells (HPCs) which enables them to proceed through
      limitless numbers of cell cycles and to become resistant to cell death. Increased
      proliferation renders these cells vulnerable to acquiring mutations and may favor
      leukemic transformation. Here, we review how deregulated cell cycle control
      contributes to increased proliferation in AML and favors genomic instability, a
      prerequisite to confer selective advantages to particular clones in order to
      adapt and independently proliferate in the presence of a changing
      microenvironment. We discuss the connection between differentiation and
      proliferation with regard to leukemogenesis and outline the impact of specific
      alterations on response to therapy. Finally, we present examples, how a better
      understanding of cell cycle regulation and deregulation has already led to new
      promising therapeutic strategies.

PMID- 22957306
TI  - BRCA1 proteins regulate growth of ovarian cancer cells by tethering Ubc9.
AB  - Mutation in the BRCA1 gene is associated with increased risk for hereditary
      breast and ovarian cancers. In sporadic ovarian tumors, BRCA1 dysfunction is
      thought to be common. BRCA1 is a nuclear-cytoplasm shuttling protein. Our group
      has previously reported that BRCA1 proteins, unlike K109R and cancer-predisposing
      mutant C61G BRCA1 proteins, bind the sole SUMO E2-conjugating enzyme Ubc9. In
      this study, we examined the result of altered Ubc9 binding and knockdown on the
      sub-cellular localization and growth inhibitory function of BRCA1 proteins in
      ovarian cancer cells. Using live imaging of YFP, RFP-tagged BRCA1 and BRCA1a
      proteins, our results show enhanced cytoplasmic localization of K109R and C61G
      mutant BRCA1 proteins in ES-2, NIHOVCAR3 and UWB 1.289 ovarian cancer cells. Down
      regulation of Ubc9 in ovarian cancer cells using Ubc9 siRNA resulted in
      cytoplasmic localization of BRCA1 and BRCA1a proteins. These mutant BRCA1a
      proteins were impaired in their capacity to inhibit growth of ES-2 ovarian cancer
      cells. Several ovarian cancer cells, including a BRCA1-null ovarian cancer cell
      line, showed higher levels of expression of Ubc9. This is the first study
      demonstrating the physiological link between loss of Ubc9 binding and loss of
      growth suppression of disease-associated mutant BRCA1a proteins in ovarian cancer
      cells. BRCA1, by turning off or on Ubc9 binding, regulates growth of ovarian
      cancers.

PMID- 22957307
TI  - RanBPM expression regulates transcriptional pathways involved in development and
      tumorigenesis.
AB  - RanBPM is a ubiquitous protein that has been reported to regulate several
      cellular processes through interactions with various proteins. However, it is not
      known whether RanBPM may regulate gene expression patterns. As it has been shown
      that RanBPM interacts with a number of transcription factors, we hypothesized
      that it may have wide ranging effects on gene expression that may explain its
      function. To test this hypothesis, we generated stable RanBPM shRNA cell lines to
      analyze the effect of RanBPM on global gene expression. Microarray analyses were
      conducted comparing the gene expression profile of Hela and HCT116 RanBPM shRNA
      cells versus control shRNA cells. We identified 167 annotated genes significantly
      up- or down-regulated in the two cell lines. Analysis of the gene set revealed
      that down-regulation of RanBPM led to gene expression changes that affect
      regulation of cell, tissue, and organ development and morphology, as well as
      biological processes implicated in tumorigenesis. Analysis of Transcription
      Factor Binding Sites (TFBS) present in the gene set identified several
      significantly over-represented transcription factors of the Forkhead, HMG, and
      Homeodomain families of transcription factors, which have previously been
      demonstrated as having important roles in development and tumorigenesis. In
      addition, the combined results of these analyses suggested that several signaling
      pathways were affected by RanBPM down-regulation, including ERK1/2, Wnt, Notch,
      and PI3K/Akt pathways. Lastly, analysis of selected target genes by quantitative
      RT-qPCR confirmed the changes revealed by microarray. Several of the genes up
      regulated in RanBPM shRNA cells encode proteins with known oncogenic functions,
      such as the RON tyrosine kinase, the adhesion molecule L1CAM, and transcription
      factor ELF3/ESE-1, suggesting that RanBPM functions as a tumor suppressor to
      prevent deregulated expression of these genes. Altogether, these results suggest
      that RanBPM does indeed function to regulate many genomic events that regulate
      embryonic, tissue, and cellular development as well as those involved in cancer
      development and progression.

PMID- 22957308
TI  - Profiling of cytokines in human epithelial ovarian cancer ascites.
AB  - BACKGROUND: The behavior of tumor cells is influenced by the composition of the
      surrounding tumor environment. The importance of ascites in ovarian cancer (OC)
      progression is being increasingly recognized. The characterization of soluble
      factors in ascites is essential to understand how this environment affects OC
      progression. The development of cytokine arrays now allows simultaneous
      measurement of multiple cytokines per ascites using a single array. METHODS: We
      applied a multiplex cytokine array technology that simultaneously measures the
      level of 120 cytokines in ascites from 10 OC patients. The ascites concentration
      of a subset (n = 5) of cytokines that was elevated based on the multiplex array
      was validated by commercially available ELISA. The ascites level of these 5
      cytokines was further evaluated by ELISA in a cohort of 38 patients. Kaplan-Meier
      analysis was used to assess the association of cytokine expression with
      progression-free survival (PFS) in this cohort. RESULTS: We observed a wide
      variability of expression between different cytokines and levels of specific
      cytokines also varied in the 10 malignant ascites tested. Fifty-three (44%)
      cytokines were not detected in any of the 10 ascites. The level of several
      factors including, among others, angiogenin, angiopoietin-2, GRO, ICAM-1, IL-6,
      IL-6R, IL-8, IL-10, leptin, MCP-1, MIF NAP-2, osteprotegerin (OPG), RANTES, TIMP
      2 and UPAR were elevated in most malignant ascites. Higher levels of OPG, IL-10
      and leptin in OC ascites were associated with shorter PFS. IL-10 was shown to
      promote the anti-apoptotic activity of malignant ascites whereas OPG did not.
      CONCLUSION: Our data demonstrated that there is a complex network of cytokine
      expression in OC ascites. Characterization of cytokine profiles in malignant
      ascites may provide information from which to prioritize key functional cytokines
      and understand the mechanism by which they alter tumor cells behavior. A better
      understanding of the cytokine network is essential to determine the role of
      ascites in OC progression.

PMID- 22957309
TI  - Vascular development in mouse lung metastases.
AB  - Dissemination of cancer cells is strongly associated with reduction in quality of
      life, worsening of prognosis, and remains the primary cause of therapeutic
      failure and high mortality in cancer. A crucial factor in the progression of
      metastases is the ability to establish a functioning blood vessel network.
      Consequently therapeutic strategies which selectively target tumor vasculature
      may hold promise for the treatment of metastatic disease. A complicating factor
      in the assessment of the efficacy of vascular targeting therapies is that the
      metastatic process can result in multiple neoplastic lesions at various stages of
      growth and vascularity in a single organ. The goal of this project was to utilize
      a rodent squamous cell carcinoma (SCCVII) model to characterize the development
      of metastatic lung lesions and their associated vasculature. Mice were injected
      with tumor cells via the tail vein to introduce a reproducible number of lung
      metastases. At various times after cell injection, lungs were removed and serial
      sections were taken throughout the lobes for morphometric analysis. Tumor volumes
      were calculated for each nodule using 2 hematoxylin and eosin (H&E) stained
      sections that were a known distance apart. Sections adjacent to those used for
      size determination were reserved for immunohistochemical staining with CD31 to
      identify blood vessels associated with each nodule. The results showed that
      although the median tumor volume increased from 0.006 to 0.51 mm(3) between 7 and
      18 days post SCCVII cell injection, a range of tumor sizes existed at all-times.
      Irrespective of the time of assessment, nodules with volumes <= 0.5 mm(3) had a
      constant vessel density while those with volumes >0.5 mm(3) showed increasing
      vessel densities with increasing size. These findings indicate that the
      methodology outlined in this study can identify metastases in various stages of
      vascular development and could therefore be applied to evaluate and distinguish
      therapeutic interventions that seek to prevent the initiation of blood vessel
      networks and those targeting already established expanding tumor vasculature.
      Examining the efficacy of such approaches, alone or in combination, in the
      treatment of metastases in a preclinical model could lead to the development of
      more effective therapeutic strategies for metastatic disease.

PMID- 22957310
TI  - Histone modifications and cancer: biomarkers of prognosis?
AB  - Epigenetic dysregulation is being increasingly recognized as a hallmark of
      cancer. Post-translational modifications of histones, in particular, are known to
      play important roles gene expression alterations in cancer development and
      progression. Given their key involvement in the various stages of carcinogenesis,
      histone modifications are also being explored as potential biomarkers of disease
      progression and prognosis. This review will therefore discuss the role of histone
      modifications in cancer biology and will explore their prognostic potential.

PMID- 22957311
TI  - A multiplex serum protein assay for determining the probability of colorectal
      cancer.
AB  - Our purpose is to develop a serum assay to determine an individual's probability
      of having colorectal cancer (CRC). We have discovered a protein panel yielding
      encouraging, clinically significant results. We evaluated 431 serum samples from
      donors screened for CRC by colonoscopy. We compared the concentration of seven
      proteins in individuals with CRC versus individuals found to be CRC free. The
      assay monitored a single peptide from each of seven proteins. Comparing CRC to
      normal samples in univariate two-sample t-tests, 6 of the 7 proteins yielded a p
      value less than 0.01. Logistic regression was used to construct a model for
      determination of CRC probability. The model was fit on a randomly chosen training
      set of 321 samples. Using 6 of the 7 proteins (ORM1, GSN, C9, HABP2, SAA2, and
      C3) and a cut point of 0.4, an independent test set of 110 samples yielded a
      sensitivity of 93.75%, a specificity of 82.89% and a prevalence-adjusted negative
      predictive value (NPV) of 99.9775% for the assay. The results demonstrate that
      the assay has promise as a sensitive, non-invasive diagnostic test to provide
      individuals with an understanding of their own probability of having CRC.

PMID- 22957312
TI  - Thyroid hormone receptor beta suppresses SV40-mediated tumorigenesis via novel
      nongenomic actions.
AB  - Accumulated evidence suggests that thyroid hormone receptor beta (TRbeta) could
      function as a tumor suppressor, but the detailed mechanisms by which TRbeta
      inhibits tumorigenesis are not fully understood. The present studies explored the
      mechanisms by which TRbeta acted to inhibit thyroid tumor development mediated by
      simian virus-40 (SV40). In mouse xenograft models, SV40 large T antigen (SV40Tag)
      immortalized human thyroid epithelial (HTori) cells rapidly induced tumors, but
      the tumor development was totally blocked by TRbeta stably expressed in HTori
      cells. Previous studies showed that the SV40Tag oncoprotein binds to and
      inactivates tumor suppressors p53 and retinoblastoma protein (Rb), thereby
      inducing tumorigenesis. Here we showed that one of the mechanisms by which TRbeta
      suppressed tumor development was by competing with p53 and Rb for binding to
      SV40Tag. The interaction of TRbeta with SV40Tag led to reactivation of Rb to
      inhibit cell cycle progression. TRbeta- SV40Tag interaction also resulted in
      reactivating p53 to increase the expression of Pten, thus attenuating PI3K-AKT
      signaling to decrease cell proliferation and to induce apoptosis. The present
      study uncovered a novel action of TRbeta as a tumor suppressor initiated via
      interfering with the recruitment of Rb and p53 by SV40Tag oncoprotein through
      protein-protein interaction, thereby acting to block tumor development.

PMID- 22307449
TI  - Speckle tracking analysis of the left ventricular anterior wall shows
      significantly decreased relative radial strain patterns in dystrophin deficient
      mice after 9 months of age.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder
      with an incidence of 1 in 3,500 male births. Early treatment of DMD
      cardiomyopathy is under investigation and echocardiographic analysis of strain
      patterns may provide measures to better quantify early treatment outcomes.
      METHODS: We compared cardiac function in 3, 9 and 12 month old dystrophin
      deficient mdx mice to wild type (C57BL10/J) using in vivo high frequency
      echocardiography (Vevo 770, VisualSonics, Inc., Toronto, CA) and 2D speckle
      tracking [Velocity Vector Imaging (VVI), Siemens Medical Solutions, Inc.,
      Malvern, PA]. Mice were anesthetized with 1-2% inhaled isoflurane and images were
      obtained using a 30 MHz transducer in modified parasternal long and short axis
      views obtained at the level of the papillary muscles. Myocardial motion was
      analyzed using VVI in single-beat reconstructed images. RESULTS: M-mode imaging
      showed significantly decreased shortening fraction in mdx mice compared to wild
      type at 12 months of age (SF% 26.6+/-3 vs. 32.2+/-2; p=0.002). Mdx mice showed
      significantly increased cardiac fibrosis at 12 months of age compared to controls
      (p<0.0001). Speckle tracking analysis of the left anterior mid ventricular wall
      segment showed significantly decreased relative radial strain in mdx mice at 9
      and 12 months (4.5+/-1.3% vs. 8.4+/-0.7%; p=0.001). There were no significant
      differences in circumferential or longitudinal strain. CONCLUSION: Mdx mice show
      significantly decreased LV anterior mid wall radial strain with mild
      cardiomyopathy after 9 months of age compared to wild type. Speckle tracking
      analysis may provide novel outcome measures for preclinical cardiac drug
      treatment studies in DMD.

PMID- 22318674
TI  - Restoration of dystrophin expression using the Sleeping Beauty transposon.
AB  - The Sleeping beauty (SB) system is a non-viral DNA based vector that has been
      used to stably integrate therapeutic genes into disease models. Here we report
      the SB system is capable of stably integrating the DeltaR4-R23/CTDelta micro
      dystrophin gene into a conditionally immortal dystrophin deficient muscle cell
      line, H2K SF1, a murine cell model for Duchenne muscular dystrophy. Genetically
      corrected H2K SF1 cells retained their myogenic properties in vitro. Moreover,
      upon transplantation DeltaR4-R23/CTDelta micro-dystrophin expression was detected
      within mdx nu/nu mice. Our data suggests the SB system is an effective way of
      stably integrating therapeutic genes into myogenic cells.

PMID- 22957315
TI  - The Northern Norway mother-and-child contaminant cohort study: implementation,
      population characteristics and summary of dietary findings.
AB  - OBJECTIVES: To describe the essential features of a new Northern Norway mother
      and-child contaminant cohort study called MISA, including its rationale, content,
      implementation and selected findings (mostly dietary). STUDY DESIGN: Cross
      sectional with longitudinal aspects. METHODS: Five hundred and fifteen eligible
      women were enrolled in early pregnancy, with 391 completing the study protocol
      that included a self-administrated food frequency questionnaire (FFQ) and
      donation of biological samples for contaminant analysis in the 2nd trimester,
      just after delivery, and 6 weeks postpartum. Macronutrient consumption was
      converted to energy intake, and the amounts of both macro- and micronutrients
      ingested were estimated. Some of the MISA findings were compared to data
      available in the Medical Birth Registry of Norway (MBRN). RESULTS: Compared to
      all 2004-2006 mothers in Northern Norway, the study cohort women were about 2
      years older and smoked less; on average, they had close to 16 years of education.
      Parity, gestational age and birth weight of the newborn were comparable as well.
      The estimated average dietary intake of 8.1 MJ per day was less than that
      recommended by the Nordic Nutritional Recommendations (NNR), but the intake of
      micronutrients per MJ complied. CONCLUSIONS: Although the final cohort sample
      size was less than targeted, the generally good comparisons observed between MBRN
      registered information for the study cohort and dropouts suggest that this
      occurrence introduced minimal bias. The agreement of the observed demographic and
      clinical characteristics of the cohort women and newborns with all births in
      Northern Norway implied acceptable external validity. Also, the dietary findings
      aligned well with Norwegian national data and guidelines and other studies, as
      did the high prevalence of breastfeeding. The MISA database is considered
      suitable for exploring associations between contaminant exposure and diet,
      enhancing our knowledge of the interplay of the physiological changes that occur
      in mothers with contaminant pharmacokinetics (including transfer to the infant
      before and after birth), and conducting prospective health studies of the
      children.

PMID- 22957317
TI  - Prevalence of the use of antihypertensive medications in Greenland: a study of
      quality of care amongst patients treated with antihypertensive drugs.
AB  - OBJECTIVES: The primary objective was to estimate the prevalence of patients
      diagnosed with hypertension using the proxy marker of antihypertensive drug
      therapy in Greenland and to compare the prevalences within the 5 health regions
      in Greenland. The second objective was to review 2 quality indicators in
      antihypertensive care. STUDY DESIGN: Observational and cross-sectional study
      reviewing electronic medical records. METHODS: Information about age and gender
      was collected from all patients receiving antihypertensive drug prescriptions
      within a 2-year period prior to the data extraction in January 2011. Only
      patients aged 20 or above were included. The age- and gender-specific prevalence
      of patients in antihypertensive treatment was calculated using the population as
      it was 1 January 2010 in Greenland as background population. A subsample
      consisting of patients in antihypertensive treatment aged 20 or above born within
      the first 5 days of each month was identified. Review of electronic medical
      records 1 year back in time (1 January 2010 onwards) was carried out and
      information on blood pressure obtained. The quality of care was evaluated with
      respect to 2 indicators: follow-up management and blood pressure level,
      respectively. RESULTS: The total number of patients in treatment with
      antihypertensive drugs was 4,462 (1,998 males and 2,464 females) corresponding to
      a prevalence of 11.4% (4,462/39,231). The prevalence was higher among females
      than among males. The prevalence increased with age and differed among the 5
      health regions. The percentage of patients in antihypertensive treatment with
      minimum 1 follow-up visit within 1 year (blood pressure measured and registered
      in a health clinic) was only 77.7%. Some 45% of patients in antihypertensive
      treatment achieved blood pressure below 140/90 mmHg. CONCLUSION: Hypertension is
      a common disorder in Greenland. The quality of antihypertensive care is
      suboptimal and leaves room for improvement. A national strategy based on
      guidelines, use of electronic drug prescriptions and recording of blood pressures
      combined with continuous monitoring the quality is recommended in order to
      prevent complications of untreated hypertension.

PMID- 22957318
TI  - ETIOLOGY OF IOP ELEVATION IN PRIMARY OPEN ANGLE GLAUCOMA.

PMID- 22957319
TI  - Medical education of students and residents - a new paradigm?

PMID- 22957321
TI  - The utility of transrectal sonoelastography in preoperative prostate cancer
      assessment.
AB  - AIM: To determine the diagnostic quality of transrectal sonoelastography (SE) in
      the prediction and localisation of prostate cancer, we prospectively examined
      patients who had undergone radical prostatectomy in our urology department.
      METHODS: From April 2010 to January 2011, 61 patients with biopsy-proven prostate
      cancer underwent preoperative transrectal gray-scale (b-mode) ultrasound and SE
      of the prostate. Cancer-suspicious areas were documented for b-mode and SE,
      dividing the prostate into six topographic sectors. Suspicious areas in both
      modalities were compared to tumour localisation in the prostatectomy specimen.
      Sensitivity, specificity, positive- and negative predictive values were
      calculated for both investigation techniques. RESULTS: Prostate cancer was
      present in 232 of 366 pathological sectors (62 %). B-mode ultrasound showed 113
      suspicious sectors, while SE indicated prostate cancer in 157 areas. The precise
      localisation of at least one pathologically confirmed cancerous lesion was
      possible in 42/61 (69 %) patients by b-mode ultrasound and 56/61 (92 %) patients
      by SE (P<0.005). The sensitivity for b-mode ultrasound was 33 % and specificity
      74 %. For SE sensitivity was 53 %, while specificity was 74 %. CONCLUSIONS: SE
      offers a more precise localisation of prostate carcinoma than conventional
      ultrasound. To investigate the possible advantages of SE in during prostate
      biopsy and its value in the prediction of extracapsular cancer further studies
      are required.

PMID- 22957320
TI  - The use of ultrasonography in learning clinical examination - a pilot study
      involving third year medical students.
AB  - BACKGROUND: Physical examination is a crucial part in medical student curricula,
      but a decline in physical examination skills was noted in the last two decades.
      The benefic role of ultrasonography (US) as an adjuvant method for clinical
      examination was evaluated in many studies, but there are different approaches
      among countries and universities. The aim of this study was to evaluate the role
      of US in learning physical exam in 3rd year medical students. METHODS: One
      hundred and four 3rd year medical students were randomly enrolled.  They were
      divided first in two equal groups (I and II, with and without US, by rotation)
      and then in smaller groups of 8-9 students. Pairs between smaller groups
      belonging to group I and II were randomly established in order to be trained and
      evaluated by the same instructor. We verified the influence of US on the
      correctness of thyroid palpation, lung percussion (inferior limit of the lung),
      and liver size estimation. They received no special training on US. After the
      learning sessions (four sessions, one hour each) a questionnaire was applied to
      each student. RESULTS: For thyroid palpation, there were no significant
      differences regarding the gland dimensions. For lung and liver palpation the
      results showed better results for some points in groups using US as adjuvant, but
      the most significant difference regarded the appreciation of self confidence (in
      favor of US-groups). The majority of the students using US appreciated as very
      useful the informations provided by US. Also, we found a clear improvement in
      detecting the upper limit of the liver comparing with the inferior limit of the
      lung, as result of better clinical skills. DISCUSSIONS AND CONCLUSION: The
      results from this pilot study proved the utility of US in learning clinical
      examination. The students can better understand the regional anatomy and can
      confirm immediately the physical findings. It is important for students to reach
      a certain level of knowledge regarding physical exam to better understand the
      role of US. Overall, we can state that use of US in the daily clinical
      examination teaching greatly improved the students' clinical examination
      abilities and that is a strong argument for integrating basic US into the medical
      school curriculum.

PMID- 22957322
TI  - Parathyroid incidentaloma detected during thyroid sonography - prevalence and
      significance beyond images.
AB  - INTRODUCTION: Parathyroid incidentaloma (PTI) designates a nodule discovered
      incidentally during thyroid sonography, and whose location and aspect suggests an
      abnormal parathyroid. Our aim was to assess the prevalence of PTI, their
      functional characteristics and to identify the factors correlated with their
      presence. PATIENTS AND METHODS: We recorded all patients detected with PTI
      between January 2009 and December 2011, in our department. Serum calcium,
      parathyroid hormone (PTH), thyroid stimulating hormone (TSH), free thyroine (FT4)
      and anti thyroid peroxidase antibodies (anti-TPO Ab) were measured. RESULTS: From
      a total of 2662 thyroid ultrasounds, 32 patients were identified with PTI
      (prevalence 1.2%). The diagnosis of a functional parathyroid adenoma was
      confirmed in 12 patients (37.5%). There was no significant difference in size,
      location, echogenicity or vascular pattern between the functioning adenomas and
      the other PTI. The only parameter correlated with the non functioning lesion was
      the multinodular pattern of the thyroid (multinodular goiter or macronodular
      autoimmune thyroiditis). CONCLUSIONS: Although rare, the ultrasound
      identification of an image suggestive for a pathological parathyroid gland
      requires the evaluation of the functioning character of the lesion, more than one
      third PTI being hyperfunctional. The concomitance of a nodular goiter decreases
      the probability of a primary hyperparathyroidism.

PMID- 22957323
TI  - Value of ultrasonography in neurilemmoma diagnosis: the role of round shape
      morphology.
AB  - OBJECTIVE: To evaluate the contribution of ultrasonography in the diagnosis of
      neurilemmoma and to establish if a round or round-like shape adds useful
      information for ultrasonographic diagnosis. METHODS: Archives of ultrasound
      findings in 203 patients (127 males and 76 females, aged 14 -72 years old, mean
      32.1 +/- 25.8) with limb mass were reviewed. The maximal and minimal diameter of
      the lesions was 78 mm and 11 mm, respectively (mean 34.7 +/- 15.6 mm). Lesions'
      morphology, size, capsule, and relationship with the adjacent nerve were
      analyzed, round-like or round shaped was focused, ratio of longitudinal maximal
      diameter and short maximal diameter (L/S) was calculated. Sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      ultrasonographic diagnosis were determined. RESULTS: In 37 patients with
      ultrasonographic suspicion of neurilemmomas, the neurilemmomas were confirmed in
      31 cases. From 166 patients with tumors presumed as being non-neurilemmoma
      lesions, 18 cases in the final diagnosis were neurilemmomas. Ultrasound had 63.3%
      sensitivity, 86.0% specificity, 56.4% positive predictive value, 89.2% negative
      predictive value, and 80.9% accuracy for the diagnosis of neurilemmoma. Round
      like or round shaped and L/S diameters ratio were not specific for neurilemmomas
      ultrasonographic appearance (P > 0.05). CONCLUSION: Ultrasound can diagnose
      neurilemmomas with high accuracy, but the round or round-like shaped and L/S
      diameters ratio have little value in ultrasonographic identification of
      neurilemmomas of the limbs.

PMID- 22957324
TI  - The role of i.v. and oral contrast enhanced ultrasonography in the
      characterization of gastric tumors. A preliminary study.
AB  - OBJECTIVE: To identify the diagnosis benefits of harmonics optimized i.v.
      contrast enhanced ultrasonography (CEUS) in the detection and characterization of
      several gastric neoplasms. MATERIAL AND METHOD: The study group included 10
      patients with gastric neoplasms, either epithelial or stromal. The examination
      included grey scale ultrasonography combined with hydrosonography and harmonics
      ultrasonography with i.v. contrast media, centered on the tumor, using the
      surrounding normal gastric wall as witness.  All cases were examined by
      endoscopy, followed by a pathology report and eight of the patients underwent
      surgery. CEUS followed the dynamics of the contrast media during the arterial (up
      to 30 seconds since administration) and venous (30 to 60 seconds since
      administration) phases. The characteristics of contrast uptake in the region of
      interest were also studied. RESULTS: In gastric tumors an non-homogeneous uptake
      was registered during the arterial phase followed by contrast wash-out during the
      venous phase. In stromal tumors (GIST) there was an accelerated and uniform
      uptake in the arterial phase, while the wash-out was delayed. CEUS was able to
      show the masses in all cases. The aspect of the lesions on the grey scale images 
      infiltration of polyp - consolidated the diagnosis. CONCLUSIONS: The analysis of
      the cases included in the study proved that CEUS represents a promising method in
      the characterization of infiltrative and proliferative gastric tumors. The
      information must be combined with those obtained from the 2D harmonics ultrasound
      exam. Extended studies, on a higher number of cases, are necessary in order to
      demonstrate the practical use of the method.

PMID- 22957325
TI  - Preterm screening by transfontanelar ultrasound - results of a 5 years cohort
      study.
AB  - OBJECTIVES: Intracranial hemorrhages (ICH) might be the cause of significant
      psycho-motor or cognitive impairment in preterm babies. A 5 year cohort study
      performed in the IOMC was aimed  at  determining the prevalence and proportion of
      the main types of ICH diagnosed by transfontanelar (TF) ultrasound among admitted
      preterms, along with the neuro-developmental effects on a  12 month follow-up
      period. MATERIAL AND METHODS: In the above mentioned period all enrolled newborns
      were examined by TF ultrasound according to a common standardized protocol. The 4
      grade Papile ICH classification was used for all examined subjects. In order to
      determine the potential neurological sequels we performed a 12 month neurological
      follow-up of all 292 patients in the study group. RESULTS: The prevalence of all
      types ICH diagnosed by systematic TF ultrasound was 20.4 %. The most prevalent
      type of ICH was peri-intraventricular: 40% grade I and  33 % grade II, with no
      major neurological sequels For both the correlation to the neurological outcome
      was statistically significant (p < 0.05). Severe neurological sequels were
      associated with grade III and IV, but the correlation was found to be
      statistically significant (p < 0.05) only for grade IV hemorrhages. A severe
      neurological outcome was of statistical significance only for the cerebellar
      hemorrhage outcome, although a similar pattern was also observed for the thalamic
      hemorrhages. CONCLUSION: Systematic TF screenings for preterm is useful for early
      diagnosis and staging which might improve the management of rehabilitation
      therapies, and provide appropriate information on the disease outcome as well as
      influencing the quality of parental counseling.

PMID- 22957326
TI  - Using ultrasonography as a teaching support tool in undergraduate medical
      education - time to reach a decision.
AB  - Medical education and the process of teaching and learning, respectively, are
      constantly changing. This is induced by the pace at which knowledge, teaching
      methodology and its related tools are updated, the use of simulation, virtual
      depiction and the use of static and/or dynamic images. In this respect, X-ray
      images have been used in the understanding of macroanatomy ever since the
      beginning of the last century. Starting with the 1990s, when high-performing and
      relatively less costly equipment started to emerge, several experts in the field
      of education anticipated the huge resource that ultrasound could become in the
      field of medicine. The method is easy to understand, intuitive and available to
      anyone studying human anatomy and, subsequently, the major pathological issues
      during undergraduate medical studies. The present paper  reviews the attempts
      made at using ultrasound as an educational support tool, from the first
      experiences in teaching anatomy (Hannover Medical School, 1996) until the recent
      development of an entire medical university curriculum integrating ultrasound
      (University of South Carolina, School of Medicine, 2006-2011). It is an exciting
      journey proving beyond any doubt that the method should be learned, understood
      and developed in medical schools from the undergraduate stage, together with the
      other clinical skills.

PMID- 22957327
TI  - Ultrasonography of the hip.
AB  - A complete physical examination of the hip is often difficult due to its size and
      deep position. During the last two decades, ultrasonography (US) of the hip has
      been widely accepted as a useful diagnostic tool in patients with hip pain and
      /or limited range of motion. It is commonly used in both adults and children.
      This technique allows evaluation of different anatomical structures and their
      pathological changes, such as joint recess (joint effusion, synovial
      hypertrophy), changes within the bursae (bursitis), tendons and muscles
      (tendinopathy, ruptures, calcifications), as well as changes in the bony profile
      of the joint surfaces, ischial tuberosity, and greater trochanter (erosions,
      osteophytes, calcific deposits). US is very useful for guided procedures in hip
      joint and periarticular soft tissues under direct visualization. The needle
      aspiration of synovial fluid and steroid injections are commonly-applied
      activities in daily rheumatology practice. The relatively limited acoustic
      windows available to the US beam are the principal limitations to hip US.
      Therefore, conducting a detailed examination of some important structures
      together with the interpretation of Doppler signal (sometimes undetectable) is
      not easy, requiring good knowledge of the modality. The aim of this review is to
      analyze the current literature about US of the hip and to describe the most
      frequently-observed normal and pathological findings.

PMID- 22957328
TI  - Liver elastography for the diagnosis of portal hypertension in patients with
      liver cirrhosis.
AB  - Progressive hepatic fibrosis is a feature of almost all chronic liver diseases.
      In their final stage, advanced cirrhosis, the clinical signs are diagnostic, but
      compensated liver cirrhosis is not always easy to diagnose. Apart from liver
      biopsy, serologic and elastographic non invasive methods for the evaluation of
      fibrosis severity were developed in the last few years. Studies have been made in
      order to assess their value for predicting the occurrence of cirrhosis
      complications, particularly portal hypertension. Both Transient Elastography and
      ARFI elastography are valuable methods for the early diagnosis of cirrhosis.
      While TE is a promising method for predicting the presence of portal hypertension
      in cirrhotic patients, the diagnostic accuracy of ARFI in the liver seems to be
      poor. Probably the accuracy of ARFI elastography can be significantly increased
      if spleen stiffness is assessed, alone or in combination with liver stiffness and
      other parameters.

PMID- 22957329
TI  - Ultrasound in the assessment of musculoskeletal involvement in systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is a chronic connective disease in which the
      musculoskeletal involvement affects especially the hands and feet. Ultrasound
      (US) represents an important tool in the assessment of the joint and soft tissue
      involvement in this rheumatic disorder. Few authors have investigated the role of
      US in the evaluation of joints and peri-articular tissues in SSc patients. The
      current available literature regarding US applications in the assessment of
      musculoskeletal involvement in SSc has shown  that US seems to be a useful tool 
      in detecting the presence of inflammatory and structural abnormalities involving
      both joints and soft tissues. The aim of the present paper is to review the role
      of US in the assessment of musculoskeletal involvement in SSc.

PMID- 22957330
TI  - Ultrasound-guided injections in the middle and lower cervical spine.
AB  - Injection therapies play a major role in the treatment of cervical pain and are
      becoming integral parts of a multidisciplinary approach in treatment and
      rehabilitation of such patients. Pararadicular- and facet-joint injections in the
      cervical spine are preferentially performed under computed tomography (CT) or
      fluoroscopy-guidance. In this article we present an alternative, simple and easy
      to learn step by step US-guided technique for injection therapy in the cervical
      spine.

PMID- 22957331
TI  - Musculoskeletal sonoelastography. Pictorial essay.
AB  - Ultrasonic elastography (real-time elastography, sonoelastography) is a new
      ultrasound technique being one of the imaging mainstream in the last few years
      being used for characterizing soft tissue lesions, like breast, thyroid, prostate
      and lymph nodes. Musculoskeletal pathology was one of the first applications of
      sonoelastography, but, nevertheless the method is not yet standardized. The
      purpose of this pictorial essay is to briefly describe the technique and to
      exemplify the aspects of a variety of musculoskeletal pathologies.

PMID- 22957332
TI  - Papillary renal cell carcinoma in the transplanted kidney - a case report
      focusing on contrast enhanced ultrasound features.
AB  - The purpose of the case report is to show that contrast enhanced ultrasound
      (CEUS) is an important imaging modality for patients with impaired renal function
      in detecting, characterizing and excluding renal cell carcinoma (RCC) in
      transplanted kidneys. To our knowledge this is the first report of CEUS in a
      tumour of a kidney transplant. CEUS is feasible, reveals comparable results to
      computed tomography and should be concerned as the method of choice for patients
      with impaired renal function like renal graft recipients.

PMID- 22957333
TI  - Unilateral painful, swollen and erythematosus knee. Case report.
AB  - Musculoskeletal ultrasound (US) is gaining an increasing role in the assessment
      of a variegate set of joint and periarticular soft tissues abnormalities in
      rheumatology. In addition, US represents a useful technique in guiding local
      procedures such as aspiration of fluid collections and injections within the
      joints and periarticular musculoskeletal structures. We recently performed US in
      a patient with unilateral painful, swollen and erythematosus knee. Pre-patellar
      bursitis was demonstrated, without any signs of intra-articular abnormalities. US
      guided aspiration of local effusion was performed; synovial fluid analysis
      demonstrated septic bursitis. Appropriate treatment determined the complete
      remission.

PMID- 22957334
TI  - Prenatal ultrasound diagnosis of open spinal dysraphism in the cervical
      verterbrae. Case report.
AB  - Spinal dysraphisms are lesions that can be identified at ultrasound screening
      examination from the second trimester of pregnancy, the majority being localized
      in the lumbosacral region.  We present the case of prenatal ultrasound diagnosis
      of a 18 weeks fetus with cervical open dysraphism, a rare localization of open
      spinal dysraphisms. The alteration of cerebral normal anatomy was first
      identified; further examination showed the spinal defect with cervical location
      associated with a posterior cystic mass, the meningomyelocele.

PMID- 22957335
TI  - Pseudoaneurysma of the external jugular vein communicating with the internal
      jugular vein. Case report.
AB  - True and false aneurysmas (pseudoaneurysmas) of veins are very rare conditions.
      We present the case of a 58 year old woman with a progressive spheric enlargement
      with pusatile character of the right laterocervical area. Ultrasonography
      established the diagnosis showing the vascular mass with turbulent flow belonging
      to the external jugular vein and the communication with the internal jugular
      vein.. The particularities of this case are the absence of an obvious etiology
      and the particular variant of flow direction from internal towards the external
      jugular vein. To the best of our knowledge, this is the first case of
      pseudoaneurysma of the external jugular vein reported in literature.

PMID- 22957336
TI  - Quiz. The quadriceps tendon lesion.

PMID- 22957337
TI  - Tracing nanoparticles in vivo: a new general synthesis of positron emitting metal
      oxide nanoparticles by proton beam activation.
AB  - The synthesis of (18)F-labelled positron emitting NPs by direct irradiation of
      (18)O-enriched aluminum oxide NPs with 16 MeV protons is reported.
      Biodistribution studies of the labelled particles after intravenous
      administration were performed in male rats using positron emission tomography.
      The simple and general activation strategy can be applied to any in situ prepared
      core metal oxide particle for direct use or subsequent bio-compatible coating or
      encapsulation followed by functionalization.

PMID- 22957338
TI  - Discrimination of nerve gases mimics and other organophosphorous derivatives in
      gas phase using a colorimetric probe array.
AB  - A colorimetric array for the chromogenic discrimination of organophosphorous
      derivatives in gas phase has been developed.

PMID- 22957339
TI  - Fluorogenic detection of hydrogen sulfide via reductive unmasking of o
      azidomethylbenzoyl-coumarin conjugate.
AB  - Selective detection of hydrogen sulfide was achieved with 7-o-2'
      (azidomethyl)benzoyl-4-methylcoumarin via analyte mediated reductive removal of
      the 2'-(azidomethyl)benzoyl moiety and concurrent generation of fluorescent 7
      hydroxy-4-methylcoumarin.

PMID- 22957340
TI  - Real-time monitoring biomarker expression of carcinoma cells by surface plasmon
      resonance biosensors.
AB  - A novel surface plasmon resonance (SPR) biosensor which is capable of monitoring
      proteomic biomarker secretion from living cells is reported here. Vascular
      endothelial growth factor (VEGF) secretion from living SKOV-3 ovarian cancer
      cells was measured for concept demonstration.

PMID- 22957341
TI  - Microfluidic size selective growth of palladium nano-particles on carbon nano
      onions.
AB  - Size selective growth of palladium nano-particles 2-7 nm in diameter on the
      surface of carbon nano-onions (CNOs) (derived from catalytic cracking of methane)
      in water involves pretreating the CNOs with p-phosphonic acid calix[8]arene then
      H(2)PdCl(4) followed by dynamic thin film processing under hydrogen in a vortex
      fluidic device.

PMID- 22957342
TI  - Synthesis, solvatochromism, aggregation-induced emission and cell imaging of
      tetraphenylethene-containing BODIPY derivatives with large Stokes shifts.
AB  - A series of tetraphenylethene-containing BODIPYs with emissions from visible to
      near-IR and large Stokes shifts up to 142 nm have been designed and synthesized.
      They show solvatochromic fluorescence and can be utilized as fluorescent
      visualizers for intracellular imaging.

PMID- 22957343
TI  - A label-free real time fluorometric assay for protease and inhibitor screening
      with a released heme.
AB  - A label free continuous assay for protease activity and inhibitor screening has
      been developed. A protease (trypsin) could digest hemoglobin. Free heme molecules
      were released. Strong pi-pi stacking and hydrophobic interactions with the
      perylene probe resulted in efficient quenching of the probe's monomer
      fluorescence.

PMID- 22957344
TI  - Closing the loop via advanced neurotechnologies.

PMID- 22957345
TI  - Scotland to establish its own food standards body.

PMID- 22957346
TI  - Preventive solutions needed on dangerous dogs.

PMID- 22957347
TI  - Animal health and food safety in Europe.

PMID- 22957348
TI  - Tackling a 'growing horse crisis'.

PMID- 22957349
TI  - FAO responds to PPR epidemic in the Democratic Republic of the Congo.

PMID- 22957350
TI  - Recognition for contributions to animal welfare.

PMID- 22957352
TI  - More cases of bovine neonatal pancytopenia in Scotland.

PMID- 22957353
TI  - Retraction notice to "Relationship between dopamine D2 receptor occupancy,
      clinical response, and drug and monoamine metabolites levels in plasma and
      cerebrospinal fluid. A pilot study in patients suffering from first-episode
      schizophrenia treated with quetiapine" [J Psychiat Res 44 (2010) 754e759].
AB  - This article has been retracted at the request of the Editors: please see
      Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). REASON: Key results are based
      on invalid data, according to a recent notification by the authors. The findings
      of the article are significantly related to dopamine D2 receptor occupancy data,
      obtained from a Positron Emission Tomography (PET) scan in five individuals.
      According to new evidence, PET data of two out of these individuals did not show
      a reliable signal at all, while the PET results of the remaining three subjects
      are partly invalid. As a result, the reported findings are most likely incorrect.
      The Journal of Psychiatric Research is dedicated to the highest scientific
      standards, therefore, this article has been retracted. The Editors regret if any
      misleading conclusions have been drawn from this publication, and apologies are
      offered to the readers of the journal.

PMID- 22957354
TI  - Abstracts of the 97th National Congress of the Italian Society of Orthopaedics
      and Traumatology. November 10-14, 2012. Rome, Italy.

PMID- 22957355
TI  - ECG of the month: Bigeminal rhythm X. Sinus rhythm with monomorphic ventricular
      bigeminy and ventriculophasic sinus arrhythmia.

PMID- 22957356
TI  - New era in women's care: Fight over contraceptive coverage still unsettled.

PMID- 22957357
TI  - Ready for takeoff? Growth of private health insurance exchanges still faces
      variety of hurdles.

PMID- 22957358
TI  - Largest health foundations: U.S. foundations awarding health grants, by total
      award amount, 2010.

PMID- 22957359
TI  - States with the most health information exchanges: Based on eHealth initiative's
      map of health information exchange activity in the U.S.

PMID- 22957361
TI  - 'Window is shutting': Insurers turn focus from acquisitions to Medicaid.

PMID- 22957360
TI  - Lowering their profile: Industry lobbyists taking backseat at conventions.

PMID- 22957362
TI  - 'Unrealistic' changes: Hospitals still see challenges in Stage 2.

PMID- 22957363
TI  - Post-acute partners: Companies expanding their services through ventures with
      ACOs.

PMID- 22957364
TI  - Heart surgery can result in several medical complications.  Some post-surgical
      conditions, such as insomnia, can be managed easily or will fade over time, while
      others require further treatment.

PMID- 22957365
TI  - I've heard that statins can can help lower C-reactive proteins (CRP) levels. I'm
      65, but I don't take a statin because my cholesterol is low. Should I be
      concerned about CRP? I have a family history of heart disease.

PMID- 22957366
TI  - I recall reading that the motion-sickness drug Dramamine could help if you're
      having a heart attack.  Is that true?

PMID- 22957367
TI  - Is there an age limit for weight loss surgeries, such as bariatric surgery? I'm
      61, diabetic and very overweight. I'm eating healthier now, but I think I need a
      more drastic step to improve my health sooner than later.

PMID- 22957368
TI  - EquiFrame: a framework for analysis of the inclusion of human rights and
      vulnerable groups in health policies.
AB  - Ensuring that health policies uphold core concepts of human rights and are
      inclusive of vulnerable groups are imperative aspects of providing equity in
      health care, and of realizing the United Nations' call for Health for All. We
      outline the process of extensive consultation undertaken across countries and
      stakeholders culminating in the development of EquiFrame, in conjunction with its
      associated definitions of core concepts of human rights and vulnerability.
      EquiFrame is a systematic policy analysis framework that assesses the degree to
      which 21 core concepts of human rights and 12 vulnerable groups are mentioned and
      endorsed in health policy documents. We illustrate the scope of the framework by
      reporting the results of its application to two health policy documents from
      (Northern) Sudan: the rather generalist Health Policy of (Northern) Sudan, and
      the more specific National Drug Policy of (Northern) Sudan. We outline some
      limitations of the framework and highlight issues for considerationin its
      interpretation. EquiFrame offers a systematic approach to analyzing
      andfacilitating the inclusion of core concepts of human rights and vulnerability
      in existing or developing health policies and ultimately to promoting greater
      equity in health care.

PMID- 22957369
TI  - [What is wrong with the feet?].

PMID- 22957370
TI  - [Survey results of the KBV physician monitor. Much work, little time - happy in
      spite of that].

PMID- 22957371
TI  - [Early detection counts. Sending the black skin cancer to the knife].

PMID- 22957372
TI  - [Primary prevention of malignant melanoma: control of irresponsible behavior,
      "Sizzling two times a year in Mallorca" (interview by Dr. Elke Oberhofer)].

PMID- 22957373
TI  - [Your patient wants to become active in sports. Are dangerous arrhythmias a
      threat?].

PMID- 22957374
TI  - [Control of doping. That is relevant for more than Olympic competitors].

PMID- 22957375
TI  - [Dialysis dependent diabetic patient. Why does perspire so much?].

PMID- 22957376
TI  - [Post laryngectomy status. How can significant mucus formation be controlled?].

PMID- 22957377
TI  - ["Patient with reflux" does not respond to proton pump inhibitors. Only operate
      on confirmed reflux!].

PMID- 22957378
TI  - [Therapy of gout. "Uric acid less than 6 mg/dl is the general consensus"
      (interview by Wiebke Kathmann)].

PMID- 22957379
TI  - [Allergy or histamine intolerance? Cheilitis caused by soy sauce].

PMID- 22957380
TI  - [Tired, apathetic, weak. Does this man need testosterone?].

PMID- 22957381
TI  - [Meta-analysis confirms positive effect. Testosterone substitution in heart
      failure?].

PMID- 22957382
TI  - [Late parents].

PMID- 22957383
TI  - [Medical risks of late paternity].

PMID- 22957384
TI  - [Reproductive aging].

PMID- 22957385
TI  - [Medical checkup guidelines for your sportive comeback].

PMID- 22957386
TI  - [Diagnosis and therapy of osteoporosis--specific features in the elderly].

PMID- 22957387
TI  - [Current therapeutic strategies for hepatocellular carcinoma].

PMID- 22957388
TI  - [Kidney and eye in diabetes: diagnosis and therapy, useful aspects for general
      practitioners].

PMID- 22957389
TI  - [Rational treatment of ulcerative colitis--local or systemic therapy? Surgery?].

PMID- 22957390
TI  - [Hypercholesterolemia: when statins are not enough or not tolerated. With
      combination therapy to LDL cholesterol target goal].

PMID- 22957391
TI  - [Psychoanalytic developmental psychology].

PMID- 22957392
TI  - [Resilience: an interdisciplinary approach to concept and findings].
AB  - First, the concept of the term "resilience" is introduced and summarized as an
      adaptive, dynamic "buffering process" of children's mental power of resistance
      against biological, psychological and psychosocial development risks.
      Subsequently, based on a critical discussion of the current research findings,
      protective factors are presented, which is followed by an approach to the concept
      of resilience from interdisciplinary perspectives. The latest findings from
      developmental neurobiology show that genetic as well as environmental factors
      have their important share in the development of resilience. This builds a bridge
      to the consideration of resilience with regard to attachment theory. Accordingly
      secure attachment could be seen as a condition for a resilient conduct of life.
      In this context, the concept of "earned security" is additionally taken into
      account. Furthermore, the relevance of resilience for the field of pedagogics is
      shortly and critically considered. With reference to a psychoanalytic approach to
      the concept of resilience self-regulation, internal integrity, mentalization and
      self-reflection are elaborated on, as well as the similarity to the
      psychoanalytic concept of ego strength. In conclusion, a critical discussion of
      the concept of resilience and its benefits as well as potential risks related to
      it is presented.

PMID- 22957393
TI  - [Empathy and mirror neurons. A view on contemporary neuropsychological empathy
      research].
AB  - Neurons firing both to specific actions performed by self and matching actions
      performed by others are classified as mirror neurons. Since its discovery in
      1991, this phenomenon has been surveyed in the field of motor and sensorimotor
      function and incipiently in the field of language and emotions. The research
      group of Giacomo Rizzolatti assumes that mirror neurons form the biological basis
      of compassion and thereby of affective empathic experience. The research
      regarding mirror neurons is yet in early stages and further research is required
      to specify mirror neuron systems. In view of empathy it is the insula which is of
      central importance for the recognition of disgust. The discovery of mirror
      neurons allows a comprehension of empathy as an immediate and compassionate
      partaking of a response, enabling an understanding of the other persons feeling.
      At the same time, the resonating affect remains allocated to the other person,
      distinguishing this comprehensive process from a mere emotional contagion. At
      present, the phenomenon of mirror neurons is gaining clinical relevance in the
      field of autism spectrum disorders and apoplexia. One's own ability for empathy
      as well as promoting empathetic abilities of others is of central importance for
      the clinical praxis, in particular concerning the treatment of children and
      adolescents.

PMID- 22957394
TI  - [Mentalisation and affect regulation--how the infantile self develops].
AB  - The text comprises the different elements of the psychoanalytic mentalization
      theory of Peter Fonagy et al. and tries to explain them. Part of this theory are
      above all the affect mirroring as well as the affect reciprocity theory and the
      two modes of the "as if" character and the psychic equivalence (playing with
      reality). You can find clear examples for each of these theoretical components.
      Moreover there are many correlations to other authors and their respective
      development theories: that is to Wilfred Bion, Donald Winnicott and John Bowlby.
      The text is based above all on Martin Dornes' approaches on this topic (2004,
      2006).

PMID- 22957395
TI  - [Containing, right hemisphere: projective identification as an interpersonal
      mechanism, the ability for affect regulation].
AB  - The capacity of affect regulation develops with priority in reciprocal, non
      verbal communication processes between the early caregiver and the baby. In this
      process, the projective identification plays the role of crucial means of
      communication. Processes of projective identification which emerge in therapeutic
      and educational interactions can be understood as such an early form of
      communication which contributes to the afterward-ripening of the capacity of
      affect regulation. Before the background of recent neuro-psychological findings
      it becomes clear, why the reciprocal and non-verbal communication between the
      early caregiver and infant as well as between the therapist and the patient is of
      such fundamental importance for the structural (re-) maturation of the right
      cerebral hemisphere, as well as for the connections between the left and right
      hemisphere. In case the projective identification persists as a defensive
      strategy in dealing with other people, pathological interaction circles can
      develop which can be overcome only when, for example, the other person assumes
      the role of the "regulating other".

PMID- 22957396
TI  - [Tragic, funny, instructive--mistakes in psychotherapy with children and
      adolescents].
AB  - This article refers to the felt sense of therapeutic mistakes, it does not focus
      on clear legal mistakes. Theoretical and general aspects of the scientific field
      of failure research are described. Furthermore, the authors present a model for
      the classification of different types of mistakes and illustrate how therapeutic
      mistakes/failure can be used creatively in supervision. Finally, various
      possibilities of finding a good way to deal with mistakes in therapeutic work
      with children and adolescents are discussed.

PMID- 22957397
TI  - [Music-based intervention in children].
AB  - Music-based interventions with children are an effective method in health and
      sickness treatment and in education systems. The engagement with music enables
      positive transfer effects on extra-musical developmental domains. Music therapy
      was applied primarily as a practically-oriented scientific discipline both within
      the framework of a multi-modal therapy approach as one treatment component and
      focused specifically on children with emotional disorders within a somatic
      therapy concept and in rehabilitation. The following narrative overview will
      present music therapy's working basis, treatment goals, and select outcome
      research in children from 2005-2010. There currently exists a substantial lack,
      even within empirical research, in relation to the application of music therapy
      to children. This is an opportunity to initiate a broad range of study for the
      future. Current challenges and opportunities in scientific, music-based
      intervention in the paediatric population lie in the concretization of
      differential indications (both in intervention approach and duration), replicable
      comparative therapy (alternated treatment-design), the application of a music
      therapeutic placebo requirement, as well as in the verification and analysis of
      specific music therapeutic mechanisms.

PMID- 22957398
TI  - [Using attachment measures in the context of providing expert witness through
      psychiatric assessment in family court proceedings].
AB  - Prognostic evaluation of child development in the context of his/her actual
      family situation plays an important role in family law disputes. However, there
      is a lack of empirically validated instruments to assess socio-emotional
      development in very young children. Attachment research provides instruments
      which could be utilized in clinical practice. At this, the focus should be on
      assessing the quality of parent-child-relationship and the occurrence of risky
      parenting behaviour. The article illustrates the use of attachment measures in
      the context of a family court proceeding according to subsection 1666 German
      Civil Code. Risk assessment is carried out through direct observation of the
      quality of interaction between mother and ten months old infant as well as
      through evaluation of the attachment representations of both parent caregivers.
      Instruments used are the Strange Situation Test (to assess infant attachment),
      the CARE-Index (to assess parental sensitivity), the Adult Attachment Interview,
      and the Adult Attachment Projective (to assess parental attachment
      representations).

PMID- 22957399
TI  - [Maternal affect regulation of mothers with a history of abuse in mother-infant
      interaction].
AB  - Maternal intuitive skills can be threatened as a result of severe deprivation or
      unresolved trauma in the own childhood and can even be inaccessible to the
      mother. A mother's own childhood experience of abuse maybe a risk factor for
      repeated child abuse. As a follow-up study to assess the emotional availability
      of abused mothers it was investigated how a physical or sexual abuse appears in
      the mother-child interaction and communication in the context of "cycle of abuse"
      and whether it could give effect to it. Interactions of mothers with abuse
      experience were compared with those of mothers without an abuse experience and
      evaluated five months postpartum with the Munich clinical communication scale
      (MKK). The results suggest that maltreatment experienced mothers show less
      emotion tuning to their child in a standardized interaction sequence.

PMID- 22957400
TI  - The natural history of hormone receptor-positive breast cancer.
AB  - Abstract: Approximately 70% of human breast tumors express hormone receptors
      (HRs), comprising the estrogen receptor (ER) and/or progesterone receptor
      (PR).The ER is the primary transcription factor driving oncogenesis in HR
      positive (HR+) breast cancers; it is both a target of, and predictor of response
      to, antiestrogen therapy. Unlike in other breast cancer subtypes, more than half
      of all disease recurrences in HR+ breast cancer occur 6 years or more after
      diagnosis, particularly following 5 years of adjuvant anti-estrogen therapy. Late
      relapses in HR+ breast cancer thus represent a significant clinical challenge.
      There is considerable molecular and clinical heterogeneity underlying HR+ breast
      cancers, and a limited understanding of the mechanisms underlying treatment
      resistance and late relapse. In this review, we describe the long natural history
      of HR+ breast cancer and discuss relapse patterns in relation to their
      clinicopathological and molecular characteristics. We highlight the relationship
      between tumor relapse and anti-estrogen therapy resistance, and we describe the
      concept of tumor dormancy. Finally, we review novel translational research
      strategies utilizing preclinical models and patient tumor samples, and current
      clinical strategies that address this increasingly common challenge in breast
      cancer.

PMID- 22957401
TI  - The natural history of hormone receptor-positive breast cancer: attempting to
      decipher an intriguing concept.

PMID- 22957402
TI  - Hormone receptor-positive breast cancer: the known and the unknown.

PMID- 22957403
TI  - Unfavorable, complex, and monosomal karyotypes: the most challenging forms of
      acute myeloid leukemia.
AB  - In acute myeloid leukemia, the karyotype of the leukemic cell is the most
      powerful predictor of treatment outcome. Approximately 30% of cases of AML have
      an unfavorable karyotype, and if treated with conventional chemotherapy, a
      complete response rate of about 50% and a 5-year overall survival of 10% to 20%
      are expected. Of those in the unfavorable group, almost half will have a complex
      karyotype, which is associated with a poorer outcome, and 40% of those will have
      a monosomal karyotype, which carries an even worse prognosis. The best chance for
      cure for patients with an unfavorable karyotype is seen in those who achieve a
      complete response and proceed to allogeneic transplant. For patients who are not
      candidates for aggressive therapy, preliminary data suggest that outcomes at
      least equivalent to those seen with standard chemotherapy can be obtained using
      azacitidine or decitabine.

PMID- 22957404
TI  - Acute myeloid leukemia with adverse cytogenetic risk.

PMID- 22957405
TI  - Acute myeloid leukemia: the challenge of unfavorable cytogenetics.

PMID- 22957406
TI  - Current perspectives on preoperative integrated treatments for locally advanced
      rectal cancer: a review of agreement and controversies.
AB  - The optimal approach to the diagnosis and treatment of locally advanced rectal
      cancer involves multidisciplinary, integrated management. In the past 30 years,
      survival and freedom from disease have increased, but the ideal multidisciplinary
      management remains to be determined. The preferred integrated treatment modality
      is preoperative radio(chemo)therapy followed by total mesorectal excision.
      Certain aspects of this standard are still debated, and the European and American
      approaches vary. The chief recommendations per international guidelines are
      summarized, and the next generation of integrated treatments for locally advanced
      rectal cancer is discussed.

PMID- 22957407
TI  - Going beyond systemic fluoropyrimidines with radiation therapy for rectal cancer:
      what should be the priority?

PMID- 22957408
TI  - Which rectal cancers are locally advanced?

PMID- 22957409
TI  - Cancer quackery: the persistent popularity of useless, irrational 'alternative'
      treatments.
AB  - At a time when many readily believe that vaccines cause autism, or that
      government scientists created AIDS as a weapon of black genocide, it is not
      surprising that medical quackery, especially cancer quackery, remains a
      flourishing and lucrative business throughout the developed world. This review
      provides a brief recap of its history and an overview of the various types of
      unproven or disproved cancer therapies popular now in the United States and
      elsewhere.

PMID- 22957410
TI  - The key to reducing quackery lies in healing patients and treating their
      experience.

PMID- 22957411
TI  - Quackery, placebos, and other thoughts: an integrative oncologist's perspective.

PMID- 22957412
TI  - Characterisation of the antioxidant effects of Aesculus hippocastanum L. bark
      extract on the basis of radical scavenging activity, the chemiluminescence of
      human neutrophil bursts and lipoperoxidation assay.
AB  - OBJECTIVES: Oxidative stress is increasingly recognised as a pivotal factor that
      plays a number of roles in the inflammatory response to environmental signals. It
      has been claimed that Aesculus hippocastanum extracts have antioxidant and anti
      inflammatory activity, but these claims are mainly based on the results of
      chemical reactions and folk-medicine. MATERIALS AND METHODS: The aim of this
      study was to examine whether a bark extract of Aesculus hippocastanum interferes
      with reactive oxygen/nitrogen species (ROS/RNS) during the course of human
      neutrophil respiratory bursts, and to establish the lowest concentration at which
      it still has antioxidant activity by means of luminol amplified chemiluminescence
      (LACL). We also studied its ability to counteract lipid peroxidation (LPO) in
      human cells. Before investigating its antioxidant effects on human cells, we
      analysed its scavenging activity against ABTS*+, hydroxyl radical, superoxide
      anion, and Fremy's salt (those last three by means of electron paramagnetic
      resonance (EPR) spectrometry). RESULTS: The extract of Aesculus hippocastanum
      exerted its anti-ROS/RNS activity in a concentration-dependent manner with
      significant effects being observed for even very low concentrations: 10 microg/ml
      without L-Arg, and 5 microg/ml when L-Arg was added to the fMLP test. The LPO
      assay confirmed these results, which were paralleled by the EPR study.
      CONCLUSIONS: These findings are interesting for improving the antioxidant network
      and restoring redox balance in human cells, and extend the possibility of using
      plant-derived molecules to antagonise the oxidative stress generated in living
      organisms when the balance is in favour of free radicals as a result of the
      depletion of cell antioxidants.

PMID- 22957413
TI  - Effect of Trigonella foenum-graecum seed powder on the antioxidant levels of high
      fat diet and low dose streptozotocin induced type II diabetic rats.
AB  - BACKGROUND AND OBJECTIVES: Type II diabetes is a disease characterized by chronic
      hyperglycaemia and oxidative stress. Among the natural products, Trigonella
      foenum-graecum (Fenugreek) is found to have many active bio molecules. It is used
      traditionally in Indian folk medicine to treat diabetes. MATERIALS AND METHODS:
      In the present study, the antioxidative potential of Trigonella foenum-graecum
      seed powder was assessed in high fat diet and low dose streptozotocin (35 mg/kg
      body weight) induced type II diabetic rats. Male Sprague Dawley rats were used
      for the study. Lipid peroxidation and the antioxidant activities (catalase,
      superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced
      glutathione) were measured in pancreas and liver tissues of normal, diabetic and
      diabetic + Trigonella foenum-graecum treated rats. The diabetic + glibenclamide
      treated rats served as positive control. RESULTS: Treatment of diabetic rats with
      Trigonella foenum-graecum significantly (p < or = 0.001) improved the fasting
      blood glucose levels to near normal blood glucose levels. The levels of
      thiobarbituric acid reactive substances (TBARS) were significantly higher and the
      activities of antioxidants were found to be lowered in diabetic rats, as compared
      to the normal rats. Improved activities of antioxidants and a significant decline
      in the levels of TBARS were observed in both Trigonella foenum-graecum treated
      and glibenclamide treated diabetic rats. CONCLUSIONS: Trigonella foenum-graecum,
      apart from controlling the blood glucose levels, also has antioxidant potential
      to protect the organs such as liver and pancreas against the oxidative damage
      induced by diabetes.

PMID- 22957414
TI  - Antihyperglycemic and protective effects of Trigonella foenum graecum seed powder
      on biochemical alterations in alloxan diabetic rats.
AB  - BACKGROUND: Trigonella foenum-graecum, an annual herb belonging to the family
      Leguminosae, commonly known as fenugreek, has been reported to have hypoglycemic,
      hypocholesterolemic, hyperinsulinemic and antidiabetic properties. In the present
      study, the effect of oral feeding of Trigonella foenum-graecum seed powder (TSP)
      has been studied on blood glucose, monoamine oxidase (MAO), membrane fluidity,
      neurolipofuscin content, DNA degradation and glucose transporter-4 (GLUT4)
      accumulation in the alloxan-induced diabetic rat brain. METHODS: Diabetes was
      induced by administration of alloxan monohydrate (15 mg/100 g body weight) and
      diabetic rats were treated with 2 IU insulin, per day and 5% TSP in the diet for
      21 days. RESULTS: Diabetic rats showed hyperglycemia with almost four fold high
      blood glucose levels. Increased MAO activity with correlated increase in genomic
      DNA degradation in the diabetic brain supports the hypothesis that catecholamine
      oxidation is an important source of oxidative stress, causing loss of membrane
      fluidity, increased neurolipofuscin and decreased of GLUT4 expression with
      diabetes in the brain. The present study showed that TSP treatment reversal the
      changes to near normal levels in diabetic rat brain. CONCLUSIONS: The present
      findings indicate that the TSP exerts its anti-diabetic and neuroprotective
      effects, probably mediated through a decrease in hyperglycemia and oxidative
      stress thereby ameliorating the control and management of diabetic complications.

PMID- 22957415
TI  - Evaluation of anti convulsant activity of aerial parts of Phyllanthus longiflorus
      heyne ex hook.
AB  - OBJECTIVE: To evaluate anti convulsant effect of aerial parts of Phyllanthus
      longiflorus (PHL). MATERIALS AND METHOD: Methanol extract of aerial parts of PHL
      (MPHL) was prepared by continuous hot extraction method using Soxhlet apparatus.
      MPHL at the doses 100, 200 and 400 mg/kg were administered to male albino mice by
      oral route and the activity was assessed against maximal electro shock (MES) and
      pentylene tetrazole (PTZ) induced seizure. Abolition of hind limb extension and
      onset of clonic convulsion were taken as a measure of MES and PTZ induced
      convulsion respectively. RESULTS: MPHL reduced the duration of extensor phase of
      convulsion in MES test by 62.5% (at 400 mg/kg) and also delayed the onset of
      clonic phase of convulsion in PTZ test by 50.7% (at 400 mg/kg). The activity was
      significant (p < 0.01) and comparable to the reference drug diazepam (2 mg/kg).
      CONCLUSION: Results suggest that aerial parts of Phyllanthus longiflorus are
      useful in the management of convulsion.

PMID- 22957416
TI  - Effect of some medicinal plant extracts on the oxidative stress status in
      Alzheimer's disease induced in rats.
AB  - BACKGROUND/AIM: Alzheimer's disease (AD) is a progressive neurodegenerative
      disorder. Increased oxidative stress has been shown to be a prominent and early
      feature in AD. Medicinal plants with antioxidant activities have been used
      traditionally in the treatment of several human diseases. The present study aims
      to investigate the effect of Salvia triloba and Piper nigrum plant extracts on
      the oxidative stress status in Alzheimer's disease induced in rats. MATERIALS AND
      METHODS: 70 male rats were enrolled in this study and were classified into 7
      groups (ten each). Group 1: control group, group 2: AD-induced rats by aluminum
      chloride, and served as positive control; group 3: AD group treated with
      Rivastigmine in a dose of 0.3 mg/kg b. wt. daily for three months; group 4 & 5:
      AD group treated with total extract of Salvia triloba in a dose of 750 or 375
      mg/kg b. wt. respectively, daily for three months; group 6 & 7: AD group treated
      with total extract Piper nigrum in a dose of 187.5 or 93.75 mg/kg b. wt.
      respectively, daily for three months. After three months of treatment animals'
      sera and brain samples were collected. Malondialdehyde (MDA), nitric oxide (NO)
      and total antioxidant capacity (TAC) were determined in serum while superoxide
      dismutase (SOD) in erythrocyte. Brain samples were divided sagitally into two
      portions, the first portion was separated for determination of acetylcholine
      (Ach) and acetycholinesterase (AchE). The second portion was used for
      histopathological investigation. RESULTS: The results indicated that extracts of
      Salvia triloba and Piper nigrum as well as Rivastigmine showed significant
      increase in brain Ach, serum TAC and SOD and significant decreases in brain AchE,
      MDA and NO in AD-induced rats. Moreover, histological investigation of brain
      sections showing nearly normal histological structure of hippocampus. Treatment
      with Salvia triloba in a dose of 750 mg/kg b. wt. was more powerful in protection
      from Alzheimer's disease than Piper nigrum, as indicated by both biochemical and
      histopathological findings. CONCLUSION: This study revealed that the treatment of
      AD-induced rats with Salvia triloba and Piper nigrum, total plant extracts
      significantly reduced the oxidative stress status and ameliorates the
      neurodegeneration characteristic of Alzheimer's diseases in rats. Noteworthy,
      Salvia triloba extract showed more interest in improvement Alzheimer's disease in
      rats.

PMID- 22957417
TI  - Hepatoprotective activity of Allium paradoxum.
AB  - OBJECTIVE: Recent studies show that free radicals are important mediators of
      hepatic injury induced by carbon tetrachloride. Allium (A.) paradoxum showed
      antioxidant and antihemolytic activities. This work was conduct to determine the
      possible protective effect of this plant against hepatotoxicity. MATERIALS AND
      METHODS: Subcutaneous injection of 3 ml/kg carbon tetrachloride diluted in olive
      oil (1:1 dilution) was employed for inducing acute liver toxicity. The protective
      effect of aerial parts and bulbs of A. paradoxum at flowering stage were
      determined. RESULTS: Both aerial parts and bulbs extracts at the doses 500 and
      750 mg/kg, i.p. offered significant hepatoprotective effect by reducing the serum
      marker enzymes, serum aspartate aminotransferase (AST) and alkaline phosphatase
      (ALP). Histopathological studies further confirmed the hepatoprotective activity
      of aerial parts and bulbs extracts when compared with the CCl4 treated groups.
      CONCLUSION: Extracts of A. paradoxum showed significant hepatoprotective activity
      compared with control group.

PMID- 22957418
TI  - Investigation of in vivo radioprotective and in vitro antioxidant and
      antimicrobial activity of garlic (Allum sativum).
AB  - OBJECTIVE: In this study, we aimed to assess the in vivo antioxidant potential
      via evaluating radioprotective effects in kidney and liver tissues of rats and in
      vitro antimicrobial and radical scavenger activity of garlic extract. MATERIALS
      AND METHODS: Thirty-two mature female Wistar rats were divided into four groups,
      each consisting of eight rats. Experimental groups were control group (1), GE
      group (2), irradiation group (3) and both GE and irradiation group (4). For the
      rats in two groups (group 3 and 4), irradiation was performed on a Cobalt-60 unit
      using a single fraction of 20 Gy. The GE was given to rats once a day during the
      month before irradiation and continued for five days after irradiation. The
      garlic cloves were peeled on crushed ice and 50 g of garlic was cut into small
      pieces and homogenized in 75 mL of 0.9% NaCI. The concentration of this garlic
      preparation was considered to be 500 mg/mL on the basis of weight of the starting
      material (0.5 g/mL). This extract was administered to rats by oral gavage.
      RESULTS: Our findings suggest that the use of garlic extract could be useful for
      addressing the limited therapeutic gain due to the radiation sensitivity of
      normal tissues adjacent to the tumour which are exposed to radiation, by
      strengthening the antioxidant system. In vitro and in vivo experiments seem to
      yield similar conclusions. CONCLUSIONS: It can be stated that garlic is may be
      recommended to be sufficiently included in the diets of radiotherapy patients
      considering its antioxidant and antimicrobial efficacy.

PMID- 22957419
TI  - In vitro cytotoxic, antioxidative and alpha-glucosidase inhibitory potential of a
      herbal mixture comprised of Allium sativum and Lagerstroemia speciosa.
AB  - BACKGROUND: Hyperglycemia induced over production of free radicals in the
      mitochondrial electron transport chain is now considered as one of the central
      mechanisms in the pathogenesis of diabetic complications. Allium sativum and
      Lagerstroemia speciosa contains active principles possessing anti-diabetic and
      antioxidant properties. This study is aimed at evaluating the evidence that
      supports this traditional claim and investigates the possible synergistic effect
      on these herbs when given as a herbal mixture in vitro. AIM: The present study
      investigates the cytotoxic, antioxidant and a-glucosidase inhibitory potential of
      Allium sativum (ASE), Lagerstroemia speciosa (LSE) and their combinations using
      in vitro methods. MATERIALS AND METHODS: The total phenol, total flavonoid and
      total tannin content were determined in ASE and LSE. The cytotoxic effects of
      ASE, LSE and their combination in the ratio of 1:2, 1:1 w/w were evaluated using
      3T3 L1 preadipocyte cells. Effect of ASE, LSE and its mixture on intracellular
      reactive oxygen species (ROS) production were determined by 2',
      7'dichlorfluorescein diacetate (DCF DA) staining technique in 3T3-L1 adipocytes.
      The ability of the herbal extracts and their combination to scavenge super oxide
      radicals and to inhibit alpha-glucosidase enzyme (a carbohydrate metabolising
      enzyme) were measured using in vitro methods. RESULTS: The total phenols and
      tannins were expressed as microgram (microg) of gallic acid equivalents/mg of
      extract (GAE/mg), flavonoids as microg of quercetin equivalents/mg of extract
      (QE/mg). LSE had significant higher total phenol (300.11 +/- 1.99), flavonoid
      (53.12 +/- 0.48) and tannin content (118.90 +/- 0.15) compared to ASE which
      possessed total phenol (159.93 +/- 0.87); flavonoid (9.37 +/- 0.73) and tannin
      content (80.5 +/- 0.19). The IC50 value, the concentration of the extracts that
      cause 50% inhibition or cell death was measured as an index of cytotoxicity. The
      IC50 value was found to be in the following decreasing order: 1:2 mixture (98
      microg/ml) > ASE (323.6 microg/ml) > 1:1 mixture (428.1 microg/ml) > LSE (2154
      microg/ml). The 1:1 mixture was comparatively less cytotoxic under the tested
      concentration range (1 x 10(0) pg - 1 x 10(8) pg) than 1:2 combinations. The
      results observed with lactate dehydrogenase (LDH) release were similar to that of
      cell viability assay. The 1:1 mixture (DIA-2 hereafter) was considered for
      further investigations. DIA-2 inhibited the ROS levels, which is evidenced by the
      decreased DCF fluorescence. DIA-2 could also efficiently scavenge the super oxide
      radical generated from PMS/NADH-NBT system showing an IC50 value 69.99 microg/ml,
      the IC50 value of ASE (157.7 microg/ml), LSE (20.43 microg/ml), and ascorbic acid
      (49.64 microg/ml) used as positive control. The results of in vitro a-glucosidase
      inhibitory assay showed highest IC50 value with LSE (0.3 microg/ml) and DIA-2
      (0.7 microg/ml) than ASE (136.3 microg/ml) and positive control miglitol (651.8
      microg/ml). CONCLUSIONS: DIA-2 exerts synergistic effect in scavenging the ROS
      and inhibiting the enzyme alpha-glucosidase in vitro compared to its individual
      extracts. The possible synergistic therapeutic effects may be due the presence of
      the antioxidant rich flavonoids, phenols and tannins present in LSE and ASE.

PMID- 22957420
TI  - Antioxidant and schistosomicidal effect of Allium sativum and Allium cepa against
      Schistosoma mansoni different stages.
AB  - OBJECTIVE: The schistosomicidal properties of garlic (Allium sativum) and onion
      (Allium cepa) powder were tested in vitro against Schistosoma mansoni miracidia,
      schistosomula, cercaria and adult worms. Results indicate their strong biocidal
      effects against all stages of the parasite and also show scavenging inhibitory
      effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO). MATERIALS
      AND METHODS: In the present work, the in vivo effects of A. sativum and A. cepa
      on lipid peroxide and some antioxidant enzymes; thioredoxin reductase (TrxR),
      sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) and
      glutathione reductase (GR) (as they have a crucial role in host protection
      against invading parasite) were also studied. RESULTS: The data demonstrate that,
      there was a significant inhibition in SOD, CAT, GR, TrxR and SDH in infected
      liver while, significant elevation was detected in lipid peroxide as compared to
      the normal control. The current resultS clearly revealed that, the used both
      edible plants enhance the host antioxidant system indicated by lowering in lipid
      peroxide and stimulation of SOD, CAT, GR, TrxR and SDH enzyme levels.
      CONCLUSIONS: Enhancement of such enzymes using A. sativum and A. cepa could in
      turn render the parasite vulnerable to damage by the host and may play a role in
      the antischistosomal potency of the used food ingredients.

PMID- 22957421
TI  - Biological activities of flavonoid-rich fraction of Eryngium caucasicum Trautv.
AB  - OBJECTIVES: Eryngium (E.) caucasicum was found as a new cultivated vegetable
      plant in northern Iran and used in several local foods. Little information is
      available on biological properties of E. caucasicum. In this work antioxidant
      activity of flavonoid-rich fraction of this plant was investigated by eight in
      vitro assay systems. MATERIALS AND METHODS: 1,1-diphenyl-2-picryl hydrazyl
      radical (DPPH), nitric oxide and hydrogen peroxide scavenging activities, Fe2+
      chelating ability, reducing power and hemoglobin-induced linoleic acid
      peroxidation were used to evaluate antioxidant activities. Antihemolytic
      activities were evaluated against CuOOH and H2O2 induced hemolysis in rat
      erythrocyte. RESULTS: IC50 for DPPH scavenging activity was 391.2 +/- 14.9, 706.6
      +/- 22.3 and 779.7 +/- 16.7 microg ml(-1) for aqueous (AQ), ethyl acetate (EA)
      and n-hexane (HE) fractions, respectively. There was no difference between
      reducing power of AQ fraction activity and vitamin C (p > 0.05). IC50 for NO
      radical-scavenging activity was in order of AQ (133.5 +/- 6.2 microg ml(-1)) > EA
      (350.1 +/- 14.8 microg ml(-1)) > and HE (639.9 +/- 21.7 microg ml(-1)) fractions,
      respectively. Extracts showed weak Fe2+ chelating ability. HE fraction showed
      better activity (173.5 +/- 9.6 microg ml(-1)). Extracts exhibited weak hydrogen
      peroxide scavenging activity but exhibited very good antioxidant activity against
      the hemoglobin-induced linoleic acid peroxidation. There was no significant
      difference between AQ fraction and vitamin C (p > 0.01). Fractions delayed the
      onset of the CuOOH induced hemolysis. AQ fraction showed very high total phenol
      and flavonoid contents which was higher than other fractions. High phenol and
      flavonoid content of AQ fraction may lead to its better antioxidant activity.
      CONCLUSIONS: E. caucasicum fractions exhibited different levels of antioxidant
      and antihemolytic activities in all tested models. These results can be useful as
      a starting point of view for further applications of E. caucasicum aerial parts
      or its constituents in pharmaceutical preparations.

PMID- 22957422
TI  - Antioxidant and antihemolytic activities of flavonoid rich fractions of Artemisia
      tschernieviana Besser.
AB  - OBJECTIVES: Artemisia (Asteraceae) contains more than 400 species. Many of the
      plants belonging to this genus are known to possess biological properties. In
      this study, antioxidant and antihemolytic activities of flavonoid rich fractions
      of A. tschernieviana Besser were evaluated. MATERIAL AND METHODS: Plant aerial
      parts were extracted with 60% acetone. Extract was fractionated sequentially with
      hexane (HE), ethyl acetate (EA) and water (AQ). Antioxidant and antihemolytic
      activities of these fractions were assessed. Their antihemolytic activity was
      determined by H2O2 and cumene hydroperoxide induced hemolysis models. RESULTS: AQ
      fraction showed very powerful activity in 1,1-disphenyl-2-picryl hydrazyl (DPPH)
      radical scavenging activity with IC50 = 0.12 +/- 0.01 microg ml(-1) that was
      better than controls (vitamin C, quercetin and butylated hydroxyanisole (BHA)).
      This fraction showed very powerful reducing power assay that was better than
      vitamin C (p < 0.01). EA fraction showed higher activity in scavenging nitric
      oxide with IC50 = 0.14 +/- 0.04 microg ml(-1). In iron chelating activity HE
      fraction showed the best activity (IC50 = 162.2 +/- 8.7 microg ml(-1)). In
      scavenging of hydrogen peroxide, AQ fraction showed better activity than control
      group. This fraction had higher phenol and flavonoid contents. EA fraction showed
      higher antihemolytic activity with IC50 = 728.8 +/- 29 microg ml(-1).
      CONCLUSIONS: The fractions show very good activities in studied models. Aqueous
      fractions showed better activity than the others in nearly all tested models.
      These results can be useful as a starting point of view for further applications
      of A. tschernieviana aerial parts or its constituents in pharmaceutical
      preparations after performing clinical in vivo researches.

PMID- 22957423
TI  - Adulticidal properties of Cardiospermum halicacabum plant extracts against three
      important vector mosquitoes.
AB  - OBJECTIVE: To determine adulticidal activitiy of hexane, ethyl acetate, benzene,
      chloroform and methanol leaf extracts of Cardiospermum halicacabum against Culex
      quinquefasciatus (Cx. quinquefasciatus), Aedes aegypti (Ae. aegypti) and
      Anopheles stephensi (An. stephensi). MATERIALS AND METHODS: The bioassay was
      conducted in an experimental kit consisting of two cylindrical plastic tubes both
      measuring 125 x 44 mm following the WHO method; Mortality of the mosquitoes was
      recorded after 24 h. RESULTS: The adulticidal activity of plant extracts showed
      moderate toxic effect on the adult mosquitoes after 24 h of exposure period.
      However, compared to other solvents highest mortality was found in methanol
      extract of C. halicacabum against all the three mosquitoes. Among them An.
      stephensi produce the highest LC50 and LC90 (186.00 and 346.06 ppm) values.
      CONCLUSIONS: From the results it can be concluded the crude extract of C.
      halicacabum was an excellent potential for controlling Cx. quinquefasciatus, Ae.
      aegypti and An. stephensi mosquitoes.

PMID- 22957424
TI  - Antimicrobial activity of the crude extract of Piper sarmentosum against
      methicilin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Vibrio
      cholera and Streptococcus pneumoniae.
AB  - BACKGROUND AND AIMS: The emergence of novel diseases caused by microbial
      pathogens and the undesirable side effects of certain antibiotics has been a
      recent dilemma in the medical arena. Consequently, it has stirred the discovery
      of many naturally occurring agents which could possibly provide important
      ramifications against various pharmacological targets and to combat various
      ailments. The main aim of the present study was to determine the antimicrobial
      activity of the crude methanolic extract of Piper (P.) sarmentosum against
      methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, Vibrio
      cholera and Streptococcus pneumoniae. MATERIALS AND METHODS: The plant materials
      were extracted by percolation in 70% methanol. Only the leaves were used in this
      study. Initial antimicrobial screening using disc diffusion assay was conducted
      and further screening of the antimicrobial properties in the plant was performed
      using minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC). The phytochemical constituents in the plant were evaluated
      via phytochemical screening and thin layer chromatography (TLC). RESULTS: P.
      sarmentosum inhibited the growth of MRSA with an inhibition zone of 10.0 mm.
      There was no inhibition zone observed for the other microbes tested. MIC test
      showed a value of 50mg/ml and MBC results showed no Colony Forming Unit (CFU) at
      100 mg/ml against MRSA. Phytochemical screening of the crude extract indicated
      the presence of tannins, flavonoids, alkaloids glycosides and anthraquinone. Thin
      layer chromatography (TLC) further confirmed the presence of flavonoids and
      alkaloids in the extract. CONCLUSION: P. sarmentosum has shown to have some
      antimicrobial properties against MRSA. Based on the MIC index (MBC/MIC), the
      extract exhibits bactericidal effects against MRSA. TLC analysis indicated the
      presence of flavonoids and alkaloids which could have contributed to the
      antimicrobial activity of the plant extract.

PMID- 22957425
TI  - Hypolipidemic influence of Sargassum subrepandum: mechanism of action.
AB  - OBJECTIVES: This study aimed to elucidate the role and mode of action of
      Sargassum subrepandum methanolic extract in management of dyslipidemia in adult
      female rats. MATERIAL AND METHODS: Forty adult female Sprague Dawley rats were
      assigned into four groups: (1) lean control rats fed on standard diet, (2)
      dyslipidemia control fed on the atherogenic diet, (3) lean rats orally
      administered with 100 mg/kg b. wt of Sargassum subrepandum methanolic extract and
      (4) dyslipidemia rats orally administered with Sargassum subrepandum methanolic
      extract. Plasma lipid profile, serum MDA, NO, leptin, TNF-alpha and adiponectin
      levels were demonstrated in the all studied groups. RESULTS: The results showed
      that feeding of rats with athrogenic diet caused significant elevation in plasma
      cholesterol, triglyceride, LDL, serum MDA, NO, leptin and TNF-alpha levels while,
      it produced significant decline in plasma HDL and serum adiponectin levels
      compared with lean control rats. However, treatment of dyslipidemia rats with
      Sargassum subrepandum methanolic extract induced significant improvement of
      plasma lipid profile, marked decrease in serum MDA, NO, leptin, TNF-alpha level
      in concomitant with remarkable increase in serum adiponectin level. CONCLUSIONS:
      These results indicated that Sargassum subrepandum extract plays a vital role in
      ameliorating dyslipidemia and its complications particularly oxidative stress and
      implication. This could be attributed to the hypolipidemic effect,
      antilipidperoxidative activity and antinflammatory property of Sargassum
      subrepandum methanolic extract.

PMID- 22957426
TI  - Anti-inflammatory effects of Hylomecon hylomeconoides in RAW 264.7 cells.
AB  - BACKGROUND AND OBJECTIVES: Papaveraceae serve as a rich source of various
      alkaloids which have anti-inflammatory effect. MATERIALS AND METHODS: In this
      study, we investigated the effect of Hylomecon hylomeconoides ethanol extract
      (HHE) on lipopolysaccharide (LPS)-induced NO and interleukin-6 (IL-6) production
      in RAW 264.7 cells. RESULTS: HHE inhibited LPS-induced NO and IL-6 production.
      Moreover, HHE suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW
      264.7 in a dose-dependent manner. Furthermore, major constituents,
      dihydrosanguinarine and 6-methoxydihydrosanguinarine, of the chloroform-soluble
      extract were analyzed. CONCLUSIONS: Taken together, the results of this study
      indicate that the anti-inflammatory effects of HHE may occur via the inhibition
      of NO and IL-6 expression through the down-regulation of MAP kinase (ERK1/2, p38)
      phosphorylation in RAW 264.7 cells.

PMID- 22957427
TI  - Methanolic extract of Lupinus termis ameliorates DNA damage in alloxan-induced
      diabetic mice.
AB  - Diet therapy is showing a bright future in the therapy of diabetes mellitus (DM).
      The seeds of Lupinus termis are used in the Middle East and Africa as food and in
      folklore medicine. In traditional medicine, the seeds are reputed to be effective
      for diabetes. The aim of this work was to evaluate the antigenotoxic effect of
      Lupinus termis methanolic extract (LTE) against DM oxidative stress. MATERIAL AND
      METHODS: The analysis of micronuclei (MN) and chromosomal aberrations are
      accurate cytogenetic techniques used to show chromosomal damage caused by
      clastogenic affects. The present study was designed to evaluate: (1) the effects
      of DM on bone marrow MN frequency and chromosomal aberrations, (2) the effect of
      oral treatment by gavage of LTE on MN frequency and chromosomal aberrations
      produced by DM. RESULTS: Frequencies of MN and chromosomal aberrations have been
      significantly increased in diabetic mice compared with the normal mice (p <
      0.05). LTE at a dose 25, 50 and 100 mg/kg b.wt. for 15 days groups treatment in
      diabetic mice were significantly decreased MN frequency and chromosomal
      aberrations in a dose dependent manner. CONCLUSIONS: Our results suggest that LTE
      is a suitable agent for preventing DM-induced DNA damage. To the best of our
      knowledge, this is the first report on LTE having a potential diabetes-associated
      DNA damage-protecting activity in vivo.

PMID- 22957428
TI  - Immunological and physiological parameters of Biomphalaria alexandrina snails
      exposed to Azadirachta indica plant.
AB  - BACKGROUND: Plant molluscicides could be appropriate for snail control measures
      against schistosomiasis in endemic areas. OBJECTIVES: The present study was
      undertaken to evaluate the immunological and physiological responses of
      Biomphalaria (B.) alexandrina snails to the effect of methanol extract of
      Azadirachta (A.) indica plant. MATERIALS AND METHODS: Haemolymph samples were
      collected from snails treated with LC25 from methanol extract for 1 month and
      untreated snails. The collected haemolymph samples from treated and untreated
      snails with tested plant were used for flow cytometric analysis of cell cycle.
      RESULTS: The obtained results indicated that hemolymph samples from B.
      alexandrina snails contained two morphologically distinct types of hemocytes,
      designated as Hyalinocyte and Granulocyte cells. In addition, the number of both
      snail's hyalinocytes and granulocytes and the mortality rate was significantly
      increased with treatment with A. indica extract. Phagocytosis in group treated
      with tested plant was highly significant increased than control one indicating a
      highly increase response of snail against the treatment. The lipid peroxide and
      glucose levels in hemolymph of treated snails were elevated while the protein and
      glycogen contents showed a decrease in soft tissues when compared with the
      control group. In addition, the activity level of some enzymes representing
      glycolytic enzymes as hexokinase (HK), pyruvate kinase (PK), phosphofructokinase
      (PFK), lactate dehydrogenase (LDH),and glucose phosphate isomerase (GPI);
      glycogenolytic enzymes as glycogen phosphorylase, glucose-6-phosphatase (G-6
      Pase); gluconeogenic enzymes as fructose-1-6 diphosphatase (F-D-P ase),
      phosphoenolpyruvate carboxykinase (PEPCK) was also significantly reduced in
      response to treatment. CONCLUSIONS: It was concluded that the application of
      methanol extracts of A. indica plant may be helpful in snail control as it
      interferes with the snails'immunology and physiology.

PMID- 22957429
TI  - Effects of sulforophane and curcumin on oxidative stress created by acute
      malathion toxicity in rats.
AB  - BACKGROUND AND OBJECTIVES: Organophosphate insecticides (OPIs) are widely used in
      agriculture and horticulture for controlling insects in crops, ornamentals,
      lawns, fruits, and vegetables. But, there have not yet any study about effects of
      sulforophane (SFN) and curcumin (CUR) on the oxidative stress created by acute
      toxic effects of malathion (MAL) as an OPI often causing human and animal
      poisoning. AIM: The aim of this study was to investigate the effects of SFN and
      CUR on the oxidative stress created in the lung, liver, and kidney tissues of
      rats by acute MAL toxicity. MATERIALS AND METHODS: Thirty-six mature Sprague
      Dawley rats weighing 200-250 g were used. The rats were randomly divided into six
      groups: unmedicated control, SFN, CUR, MAL control, MAL + SFN, and MAL + CUR.
      Tissue samples were analyzed for glutathione (GSH), malondialdehyde (MDA), and
      nitric oxide (NO) levels in the lung, liver, and kidney tissues. Biochemical
      parameters were measured colorimetrically by using a spectrophotometer. RESULTS:
      No statistically significantly difference was found when comparing the
      unmedicated control, SFN, and CUR groups. MAL significantly increased MDA levels
      in the liver and kidney tissues, but SFN and CUR these levels. MAL did
      significantly reduce the GSH levels, but SFN and CUR increased these levels by
      blocking the MAL effect in the liver tissues. Also, MAL significantly increased
      the NO levels, depending on the severity of the tissue damage, and SFN and CUR
      attenuated to NO levels and remained under the effect of MAL. CONCLUSIONS: SFN
      and CUR, which showed similar effects, could be used to protect against the
      oxidative stress caused by acute malathion intoxication.

PMID- 22957430
TI  - Recent highlights of metabolomics for traditional Chinese medicine.
AB  - Systems biology is an emerging science of the 21st century and has developed in
      recent years from a technology-driven enterprise to a new strategic tool in life
      sciences as well as its method and design resemble those of traditional Chinese
      medicine (TCM), a holistic approach to health that attempts to bring the body,
      mind and spirit into harmony. The technology platforms of systems biology,
      especially metabolomics could provide useful tools for facilitating drug
      discovery and development of TCM. Metabolomes of medicinal herbal medicine are
      particularly a valuable natural resource for the evidence-based TCM. Metabolomics
      adopts a 'top-down' strategy to reflect the function of organisms from terminal
      symptoms of metabolic network and understand metabolic changes of a complete
      system caused by interventions in holistic context. Its property consists with
      the holistic thinking of TCM, may beneficially provide an opportunity to
      scientifically express the meaning of evidence-based Chinese medicine, will
      greatly benefit both drug discovery and development for TCM research. Some
      successful metabolomic applications in important TCM field related to drug
      discovery and development from natural sources aims at raising the potential of
      metabolomics in reducing the gap between TCM and modern drug discovery demand,
      highlight the key role of biomarkers for drug discovery and development of
      traditional oriental medicine.

PMID- 22957431
TI  - Preparation and characterization of polymeric nanoparticles for siRNA delivery to
      down-regulate the expressions of exogenous and endogenous target genes.
AB  - Gene silencing induced by RNA interference using small interfering RNA (siRNA)
      provides a promising therapeutic approach for cancers. However, the lack of siRNA
      delivery vector has limited the development of siRNA therapy. The purpose of this
      study was to use the novel copolymer (mPEG5k-PCL1.2k)1.4-g-PEl10k to prepare
      siRNA-loaded nanoparticles for siRNA delivery. The results suggested that (mPEG5k
      PCL1.2k)1.4-g-PEl10k could load siRNA to form nanoparticles with particle size
      less than 200 nm in a narrow distribution. Moreover, a certain density of
      positive charge existed onto the surfaces of nanoparticles. MTT assay results
      demonstrated that (mPEG5k-PCL1.2k)1.4-g-PEl10k/siRNA nanoparticles showed very
      low cytotoxicity. The gene silencing efficiency of (mPEG5k-PCL1.2k)1.4-g
      PEl10k/siRNA nanoparticles was investigated through luciferase reporter gene
      assays. The expression of exogenous luciferase gene was significantly
      downregulated at a range of N/P ratio from 50 to 125, and was maximally inhibited
      at the N/P ratio of 125 with 54% and 59% reduction in MCF-7 and HepG2 cells,
      respectively. In the 4T1-luc cell line expressing luciferase stably, the
      silencing of endogenous luciferase gene also has a similar overall profile with
      maximal 54% reduction of luciferase expression. These results suggested that
      (mPEG5k-PCL1.2k)1.4-g-PEI10k/SiRNA nanoparticles could serve as a kind of highly
      efficient siRNA delivery system for down-regulating the expression of exogenous
      and endogenous target genes.

PMID- 22957432
TI  - Nano-pulverization of poorly water soluble compounds with low melting points by a
      rotation/revolution pulverizer.
AB  - We report a method for pulverizing poorly water soluble compounds with low
      melting points to nanoparticles without producing an amorphous phase using a
      rotation/revolution pulverizer. Fenofibrate, flurbiprofen, and probucol were used
      as crystalline model compounds. They were suspended in a methylcellulose aqueous
      solution and pulverized with zirconia balls by the rotation/revolution
      pulverizer. Beeswax, an amorphous compound, was also examined to investigate
      whether nano-pulverization of a compound with a low melting point was possible.
      Beeswax was suspended in ethyl alcohol cooled with liquid nitrogen and pulverized
      with zirconia balls by the rotation/revolution pulverizer. By optimizing the
      pulverization parameters, nanoparticles (D50 < 0.15 microm) of the crystalline
      compounds were obtained with narrow particle size distributions at a
      rotation/revolution speed of 1000 rpm and a rotation/revolution ratio of 1.0 when
      the vessel was 0 degrees C. Amorphous fenofibrate and flurbiprofen were not
      detected by differential scanning calorimetry or powder X-ray diffraction,
      whereas small amounts of amorphous probucol were detected. Beeswax was pulverized
      to nanoparticles (D50 = 0.14 microm) with ethyl alcohol cooled with liquid
      nitrogen. Fine nanoparticles of these poorly water soluble compounds with low
      melting points were obtained by controlling the rotation/revolution speed and
      reducing the vessel temperature.

PMID- 22957433
TI  - Osmotically controlled oral delivery of ciprofloxacin through asymmetric membrane
      capsules.
AB  - Asymmetric membrane capsules (AMCs) are based on the concept of osmotic pressure
      but are much simpler to manufacture. Further, they can be suitably optimized by
      varying the parameters like concentration of pore former, polymer, osmotic agents
      and solubility enhancers to cater the specific needs of a particular formulation.
      The main objective of the present work was to exploit the concept of AMCs for the
      controlled delivery of poorly soluble anti-infective drugs. Ciprofloxacin was
      chosen as the model drug. Nine AMCs (F1-F9) with varying concentrations of
      cellulose acetate [CA] (polymer-12% w/v, 16% w/v and 20% w/v) and glycerol (pore
      former- 50% w/w, 60% w/w and 70% w/w of polymer) were prepared. AMCs F1-F3 were
      discarded because of poor rigidity. 18 formulations (F4A-F9C) were prepared with
      the remaining 6 AMCs by varying concentrations of mannitol in the core (osmogen
      15% w/w, 25% w/w and 50 % w/w of drug). F6C prepared with 16% CA, 70% glycerol
      and 50% mannitol gave highest release (57.93 +/- 0.93 %) after 12 h. Scanning
      electron microscopy revealed asymmetric structure of the membrane and osmotic
      release (zero order) through pores formed in situ was confirmed. Three
      concentrations of tartaric acid were used in F6C (T1-5%, T2-15%, T3-20%) for
      further optimization. T3 gave maximum release after 12 h (82.21 +/- 0.71%) and
      was selected as final optimized formulation. The study concluded that AMCs
      containing a suitable osmogen and a solublizer, can successfully deliver poorly
      soluble anti-infective drugs in a controlled manner.

PMID- 22957434
TI  - In vitro and in vivo evaluation of novel osmotic pump tablets of isosorbide-5
      mononitrate containing polyvinyl pyrrolidone (PVP) for controlled release.
AB  - A novel osmotic pump tablet with ethyl cellulose (EC) and polyvinyl pyrrolidone
      (PVP) as the semipermeable membrane and isosorbide-5-mononitrate (5-ISMN) as the
      model drug was formulated in this study. Zero order release kinetics were
      attained by avoiding aging during storage. Drug release increased with an
      increase in the percentage of PVP K30 in the semipermeable membrane. However,
      drug release decreased with increased coating weight. Drug release rates
      decreased continuously for tablets coated with EC/PEG4000 and cellulose acetate
      (CA)/PEG4000. This tendency was more marked with longer storage time. However,
      there was little change in drug release rates for tablets with a semipermeable
      membrane of EC/PVP K30 at 6, 12 or 24 months. The weight loss test also validated
      the results mentioned above. The relative bioavailability of the osmotic-pump
      tablets against the reference formulation in single and multiple dose regimens
      was 116.7 and 106.5, respectively. This means that the bioavailability of osmotic
      pump tablets using PVP as the plasticiser was equal to that of the reference
      formulation. In general, 5-ISMN osmotic pump tablets with a semipermeable
      membrane composed of EC/PVP K30 may be useful in providing constant drug delivery
      with minimum fluctuations during longer storage time.

PMID- 22957435
TI  - Modulation of drug release from nanocarriers loaded with a poorly water soluble
      drug (flurbiprofen) comprising natural waxes.
AB  - In this study, flurbiprofen (FLB) Solid Lipid Nanoparticles (SLN) composed from a
      mixture of beeswax and carnauba wax, Tween 80 and egg lecithin as emulsifiers
      have been prepared. FLB was incorporated as model lipophilic drug to assess the
      influence of matrix composition in the drug release profile. SLN were produced by
      microemulsion technique. In vitro studies were performed in Phosphate Buffered
      Saline (PBS). The FLB loaded SLN showed a mean particle size of 75 +/- 4 nm, a
      polydispersity index approximately 0.2 +/- 0.02 and an entrapment efficiency (EE)
      of more than 95%. Suspensions were stable, with zeta potential values in the
      range of -15 to -17 mV. DSC thermograms and UV analysis indicated the stability
      of nanoparticles with negligible drug leakage. Nanoparticles with higher beeswax
      content in their core exhibited faster drug release than those containing more
      carnauba wax.

PMID- 22957436
TI  - Evaluation of insulin lispro and biosynthetic human insulin in pulmonary
      absorption: in vivo and in vitro studies.
AB  - OBJECTIVE: To compare the pulmonary absorption characteristics of two insulin
      solutions-humalog (insulin lispro) and Novolin R (Biosynthetic Human insulin)
      with in vivo and in vitro methods. METHODS: Investigate the pharmacodynamics in
      Sprague Dawley (SD) rat model (in vivo studies) and permeability across Rana
      catesbeiana pulmonary membrane (in vitro studies) of Biosynthetic Human insulin
      (BHI) and insulin lispro (LI) at different doses. RESULTS: Both of the insulins
      could reduce blood glucose levels promptly after pulmonary administration. But LI
      showed a better tendency on hypoglycemic effect than BHI in the in vivo studies.
      In the in vitro studies, the apparent permeability coefficient (Papp) for BHI and
      LI were almost constant with increasing concentrations, which implied that
      insulin maybe passively diffuse through the Rana catesbeiana pulmonary membrane
      barrier. Interestingly, the Papp of LI was obviously higher than that of BHI,
      indicating that the permeability of LI across Rana catesbeiana pulmonary membrane
      was more effective than that of BHI. CONCLUSION: These in vitro and in vivo
      results suggested that LI was easier to be absorbed in the lung than BHI and Rana
      catesbeiana pulmonary membrane had a potential ability, as a transport model, to
      predict in vivo pulmonary absorption of insulin.

PMID- 22957437
TI  - Influence of 50-nm polystyrene particles in inducing cytotoxicity in mice co
      injected with carbon tetrachloride, cisplatin, or paraquat.
AB  - The toxicity of nanomaterials has yet to be fully investigated. In particular,
      the interactions between nanomaterials and therapeutic drugs require further
      study. We investigated whether nano-sized polystyrene particles affect drug
      induced toxicity. The particles, which are widely used industrially, had
      diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals
      tested were carbon tetrachloride, cisplatin (a popular anti-tumor agent), and a
      widely used herbicide, paraquat. Mice were treated intraperitoneally with either
      carbon tetrachloride (0.01 ml/kg), cisplatin (100 micromol/kg) or paraquat (50
      mg/kg), with or without intravenous administration of polystyrene particles. All
      treatments in the absence of the nanoparticles were non-lethal and did not result
      in severe toxicity. However, when mice were injected with paraquat or cisplatin
      together with polystyrene particles, synergistic, enhanced toxicity was observed
      in mice injected with NPP50. These synergic effects were not observed in mice co
      injected with NPP200 or NPP1000. These findings suggest that further evaluation
      of the interactions between polystyrene nano-particles and drugs is a critical
      prerequisite to the pharmaceutical application of nanotechnology.

PMID- 22957438
TI  - Inhibition potential of glimepiride (gli) towards important UDP
      glucuronosyltransferase (UGT) isoforms in human liver.
AB  - The aim of the present study was to investigate the inhibitory potential of
      glimepiride towards important UDP-glucuronosyltransferase (UGT) isoforms in human
      liver, which play a key role in the elimination of drugs. The recombinant UGT
      enzymes were used as enzyme source, and a nonspecific substrate 4
      methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100
      microM of glimepiride inhibited UGT1A1, UGT1A3, UGT1A6, UGT1A9, UGT2B7 and
      UGT2B15 by 54.7%, 43.1%, 100%, 70.5%, 32.7 and 37.2%, respectively. Given that
      glimepiride exhibited strong inhibition towards UGT1A6, further inhibitory
      kinetic behaviour was determined. Glimepiride exerted concentration-dependent
      inhibition towards UGT1A6. Both Dixon and Lineweaver-Burk plots demonstrated that
      inhibition of UGT1A6 was best fit for noncompetitive inhibition type, and the
      inhibition kinetic parameter (Ki) was calculated to be 59.8 microM. Given that
      UGT1A6 plays a key role in detoxification of many drugs, more attention should be
      given when glimepiride was co-administered with the drugs mainly undergoing
      UGT1A6-mediated metabolism.

PMID- 22957439
TI  - The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12
      cells apoptosis induced by 6-hydroxydopamine.
AB  - 6-Hydroxydopamine (6-OHDA) is a widely used dopaminergic neurotoxin that leads to
      cell apoptosis in vivo and in vitro, and is a widely accepted experimental model
      of neurodegeneration in Parkinson's disease. However, the molecular mechanisms
      responsible for 6-OHDA-induced cell apoptosis are unclear. We found that the
      treatment of PC12 cells with 6-OHDA resulted in a significant decrease in cell
      viability and elevated apoptosis as detected by MTT assay, Hoechst 33258
      staining, and flow cytometry. In addition, 6-OHDA induced a time-dependent
      phosphorylation of ERK1/2 at Thr-202/Tyr-204 and of Raf-1 at Ser-338, but a
      decreased level of Raf-1 phosphorylation at Ser-259. Phosphorylation of ERK1/2 at
      Thr-202/Tyr-204 and Raf-1 at Ser-338 were inhibited by the Raf-1 inhibitor
      GW5074, while the ERK1/2 pathway inhibitor U0126 decreased phosphorylation of
      ERK1/2. Furthermore, 6-OHDA-induced PC12 cells apoptosis was suppressed by GW5074
      and U0126. Our results suggest that GW5074 and U0126 act as neuroprotants against
      6-OHDA toxicity in PC12 cells by modulating Raf-1/ERK1/2 signaling systems.

PMID- 22957440
TI  - Necroptosis contributes to the cyclosporin A-induced cytotoxicity in NRK-52E
      cells.
AB  - Cyclosporin A (CsA) induces renal tubular epithelial cells apoptosis and necrosis
      following in vitro exposure. The mechanisms of CsA-induced apoptosis have been
      studied intensively, whereas the mechanisms of necrosis remain to be elucidated.
      Necroptosis has been described as programmed necrosis. This study investigated
      the ability of CsA to induce necroptosis in the rat tubular cell line NRK-52E.
      The NRK-52E cells were incubated with CsA for 24 hours with or without
      necrostatin-1 (Nec-1). The majority of the NRK-52E cells died of necrosis as
      indicated by LDH leakage, Hoechst 33342/PI staining, and flow cytometry analysis.
      Cell death was significantly reduced by Nec-1 pretreated before CsA exposure. CsA
      induced apoptosis and necrosis were also compared in NRK-52E cells with or
      without knockdown of receptor interaction protein 3 (RIP3) expression using small
      interfering RNA. Moreover, the role of reactive oxygen species (ROS) in CsA
      induced cell death was also attempted. The result suggests that necroptosis
      contributes to the CsA-induced cytotoxicity in NRK-52E cells. Meanwhile, RIP3 and
      ROS are involved in CsA-induced necroptosis. To our knowledge, this is the first
      report on necroptosis in CsA-induced renal tubular cell death pathways, which
      might offer a novel protective target for CsA nephrotoxicity.

PMID- 22957441
TI  - Betulinic acid exerts immunoregulation and anti-tumor effect on cervical
      carcinoma (U14) tumor-bearing mice.
AB  - Phytochemicals used in cancer therapy and prevention are an important source.
      Betulinic acid (BetA), a lupine-type pentacyclic triterpenoid saponin from
      plants, has shown anti-tumor activity in some cell lines in previous studies. In
      this paper, its anti-tumor effect and the possible mechanisms were investigated
      in U14 tumor-bearing mice. The results showed that BetA (100 mg/kg and 200 mg/kg)
      effectively suppressed tumor growth in vivo. Compared with the control group,
      BetA significantly improved the levels of IL-2 and TNF-alpha in tumor-bearing
      mice and increased the number of CD4+ lymphocytes subsets, as well as the ratio
      of CD4+/CD8+ at a dose of 200 mg/kg. Furthermore, treatment with BetA induced
      cells apoptosis in dose-dependent manner in tumor bearing mice, and inhibited the
      expression of Bcl-2 and Ki-67 protein while upregulated the expression of caspase
      8 protein. The mechanisms by which BetA exerted anti-tumor effects might involve
      the induction of tumor cell apoptosis. This process is also related to
      improvement of body's immune response.

PMID- 22957442
TI  - Amorphous nanosilica particles induce ROS generation in Langerhans cells.
AB  - Generation of total intracellular reactive oxygen species (ROS) was measured in
      XS52 cells, a Langerhans cell-like line, treated with different sized amorphous
      silica particles. The results suggested that exposure to amorphous nanosilica
      particles (nSPs) with a particle size of 70 nm induced a higher level of ROS
      generation than did exposure to micron-sized amorphous silica particles. This
      finding means that it is essential to examine the biological effects of ROS
      generated after exposure to nSPs, which will provide useful information for
      hazard identification as well as the design of safer nanomaterials.

PMID- 22957443
TI  - Dermal absorption of amorphous nanosilica particles after topical exposure for
      three days.
AB  - The skin penetration and cellular localization of well-dispersed amorphous
      nanosilica particles (nSPs) with a diameter of 70 nm was analyzed in mice. Our
      results suggest that after topical exposure for three days the particles
      penetrate the skin barrier and are transported to the lymph nodes. These findings
      underscore the need to examine biological effects following dermal exposure to
      nSPs for the development of safer use of nSPs.

PMID- 22957444
TI  - ["Poorly healing black spots": what is causing these foot ulcers?].

PMID- 22957445
TI  - [Whether pain, deformities or diabetic ulcers: the feet deserve more attention].

PMID- 22957446
TI  - [Shower ban by the health department: how does one protect against legionella?
      (interview by Dr. Beate Schumacher)].

PMID- 22957447
TI  - [Do you recognize short QT syndrome? A dangerous rarity!].

PMID- 22957448
TI  - [Really an option in hypertension? Bleeding until blood pressure is normal].

PMID- 22957449
TI  - [Not just a lung toxin: ozone exposure damages the heart also].

PMID- 22957450
TI  - [Role play, chats and cybersex: the new youth drugs].

PMID- 22957451
TI  - [Food intolerance and food allergy: what may your patient still eat?].

PMID- 22957452
TI  - [Persistent backache: is it possibly a multiple myeloma?].

PMID- 22957453
TI  - [Naturopathy consultation. Herpes simplex - herpes zoster].

PMID- 22957454
TI  - [What is the best thromboembolism prophylaxis for cancer patients?].

PMID- 22957455
TI  - [Venous thromboembolism in cancer].

PMID- 22957456
TI  - [Prophylaxis of venous thromboembolism in patients with cancer].

PMID- 22957457
TI  - [High blood pressure in children and teens].

PMID- 22957458
TI  - [What to do with the acute elbow-instability? A treatment plan].

PMID- 22957459
TI  - [Asthma management: the role of new media and social networks].

PMID- 22957460
TI  - [Unexplained pelvic pain: is it endometriosis?].

PMID- 22957461
TI  - [Nephropathy and metabolic heart diseases. Cardiac risk in kidney malfunction].

PMID- 22957462
TI  - IOM outlines framework for postmarket safety.

PMID- 22957463
TI  - For health insurers, retail space available!

PMID- 22957464
TI  - Health plans won't sit out while docs, hospitals dance.

PMID- 22957465
TI  - Last chance to avoid drastic measures? Interview by John Marcille.

PMID- 22957466
TI  - Health care reform in England--commercial opportunity or another false dawn?

PMID- 22957467
TI  - Key PBM functional areas require radical transformation.

PMID- 22957468
TI  - Motivation program makes talk potent.

PMID- 22957469
TI  - Insurers find small gains in weight control with Belviq.

PMID- 22957470
TI  - Mechanistic investigation of methylphosphonate synthase, a non-heme iron
      dependent oxygenase.
AB  - Methylphosphonate synthase is a non-heme iron-dependent oxygenase that converts 2
      hydroxyethylphosphonate (2-HEP) to methylphosphonate. On the basis of experiments
      with two enantiomers of a substrate analog, 2-hydroxypropylphosphonate, catalysis
      is proposed to commence with stereospecific abstraction of the pro-S hydrogen on
      C2 of the substrate. Experiments with isotopologues of 2-HEP indicate
      stereospecific hydrogen transfer of the pro-R hydrogen at C2 of the substrate to
      the methyl group of methylphosphonate. Kinetic studies with these substrate
      isotopologues reveal that neither hydrogen transfer is rate limiting under
      saturating substrate conditions. A mechanism is proposed that is consistent with
      the available data.

PMID- 22957471
TI  - Tongue pressure and oral conditions affect volatile release from liquid systems
      in a model mouth.
AB  - The release of volatile organic compounds (VOCs) into the mouth cavity is an
      integral part of the way flavor is perceived. An in vitro model mouth with an
      artificial tongue was developed to measure the dynamic release of VOCs from
      liquid model systems [e.g., aqueous solution, oil, and oil-in-water (O/W)
      emulsions] under oral conditions. The release of seven selected VOCs was affected
      by the different polarity and vapor pressure of the compounds and their affinity
      to the liquid system media. Different tongue pressure patterns were applied to
      the liquid systems, and the release of VOCs was monitored in real time using
      proton transfer reaction-mass spectrometry. The release was significantly more
      intense for longer tongue pressure duration and was influenced by the tongue
      altering the sample surface area and the distribution of the VOCs. The role of
      saliva (artificial versus human) and the sample temperature had a significant
      effect on VOC release. Saliva containing mucin and a higher sample temperature
      enhanced the release.

PMID- 22957473
TI  - Prediction of methyl mercury uptake by rice plants ( Oryza sativa L.) using the
      diffusive gradient in thin films technique.
AB  - Rice consumption is the primary pathway for methyl mercury (MeHg) exposure at
      inland mercury (Hg) mining areas of SW China. Mechanistic information on MeHg
      accumulation in rice is, however, limited. The process of MeHg exchange between
      paddy soil and rice plants predominantly occurs in pore water. The detection of
      bioavailable MeHg in pore water is therefore important to predict MeHg uptake by
      rice plants ( Oryza sativa  L.). This study investigated MeHg dynamics and
      spatial MeHg trends in pore water during the rice growing season using the
      diffusive gradient in thin films (DGT) technique and tested the ability of DGT to
      predict MeHg uptake by rice. The MeHg uptake flux from soil to rice plants via
      roots was significantly correlated with the DGT-measured MeHg flux (R = 0.853, p
      < 0.01). Our study implies that DGT can predict the bioavailability of MeHg in
      rice paddy soil and that the DGT method can provide quantitative description of
      the rate of uptake of this bioavailable MeHg. The DGT technique is demonstrated
      as a useful indicator of the likely ecotoxicological risk that might be apparent
      where paddy rice is grown in MeHg contaminated soil.

PMID- 22957472
TI  - Enantioselective synthesis of coumarin derivatives by PYBOX-DIPH-Zn(II) complex
      catalyzed Michael reaction.
AB  - A potential pharmacologically active chiral 3-substituted 4-hydroxy-2-oxo-2H
      chromene skeleton has been synthesized by enantioselective Michael addition
      catalyzed by PYBOX-DIPH-Zn(OTf)(2) complex. The methodology has successfully been
      employed in the synthesis of (R)-Warfarin and another related compounds.

PMID- 22957474
TI  - Graphene quantum dot as a green and facile sensor for free chlorine in drinking
      water.
AB  - Free chlorine was found to be able to destroy the passivated surface of the
      graphene quantum dots (GQDs) obtained by pyrolyzing citric acid, resulting in
      significant quenching of their fluorescence (FL) signal. After optimizing some
      experimental conditions (including response time, concentration of GQDs, and pH
      value of solution), a green and facile sensing system has been developed for the
      detection of free residual chlorine in water based on FL quenching of GQDs. The
      sensing system exhibits many advantages, such as short response time, excellent
      selectivity, wide linear response range, and high sensitivity. The linear
      response range of free chlorine (R(2) = 0.992) was from 0.05 to 10 MUM. The
      detection limit (S/N = 3) was as low as 0.05 MUM, which is much lower than that
      of the most widely used N-N-diethyl-p-phenylenediamine (DPD) colorimetric method.
      This sensing system was finally used to detect free residual chlorine in local
      tap water samples. The result agreed well with that by the DPD colorimetric
      method, suggesting the potential application of this new, green, sensitive, and
      facile sensing system in drinking water quality monitoring.

PMID- 22957475
TI  - A biomechanical comparison of three hybrid linear-circular external fixator
      constructs.
AB  - OBJECTIVE: To evaluate the stiffness, displacement, ring deformation and bone
      model motion of 3 configuations of linear-circular hybrid fixator constructs
      loaded in axial compression, craniocaudal and mediolateral bending, and torsion.
      STUDY DESIGN: Biomechanical evaluation. SAMPLE POPULATION: Three hybrid construct
      configurations with 8 replicates/configuration. METHODS: Construct Ia used a
      single, 84 mm, incomplete ring and 2 tensioned olive wires to stabilize 1 bone
      segment and a primary hybrid rod with 3 fixation pins to stabilize the other bone
      segment. Constructs Ia(d)  and Ib were similar to Ia with the addition of a
      secondary diagonal hybrid rod. Construct Ib had a fixation pin inserted
      orthogonally from the diagonal rod. Constructs were loaded for 10 cycles in each
      mode of loading using a materials testing machine. Ring deformation was assessed
      by obtaining serial ring measurements. Bone model motion at the fracture gap as a
      result of loading was also calculated. RESULTS: Axial compression: constructs
      Ia(d)  and Ib were significantly stiffer than construct Ia. Craniocaudal bending:
      Construct Ib was significantly stiffer than construct Ia. Mediolateral bending:
      there were no significant differences between constructs. Torsion: Construct Ib
      was significantly stiffer than constructs Ia and Ia(d) . Permanent ring
      deformation did not occur. Bone model translational motion decreased in
      constructs Ia(d)  and Ib compared to construct Ia. CONCLUSIONS: Addition of a
      secondary hybrid rod as well as biplanar fixation pin placement improved
      construct stiffness in several loading modes.

PMID- 22957477
TI  - Better hospital nutrition needed to prevent and treat Aspergillus infections.

PMID- 22957476
TI  - Irradiation induced fluorescence enhancement in PEGylated cyanine-based NIR nano-
      and mesoscale GUMBOS.
AB  - We report on the synthesis and characterization of a PEGylated IR786 GUMBOS
      (Group of Uniform Materials Based on Organic Salts). The synthesis of this
      material was accomplished using a three step protocol: (1) substitution of
      chloride on the cyclohexenyl ring in the heptamethine chain of IR786 by 6
      aminohexanoic acid, (2) grafting of methoxy polyethylene glycol (MeOPEG) onto the
      6-aminohexanoic acid via an esterification reaction, and (3) anion exchange
      between [PEG786][I] and lithium bis(trifluoromethylsulfonyl)imide (LiNTf(2)) or
      sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in order to obtain PEG786 GUMBOS.
      Examination of spectroscopic data for this PEG786 GUMBOS indicates a large stokes
      shift (122 nm). It was observed that this PEG786 GUMBOS associates in aqueous
      solution to form nano- and mesoscale self-assemblies with sizes ranging from 100
      to 220 nm. These nano- and mesoscale GUMBOS are also able to resist nonspecific
      binding to proteins. PEGylation of the original IR786 leads to reduced
      cytotoxicity. In addition, it was noted that anions, such as NTf(2) and AOT, play
      a significant role in improving the photostability of PEG786 GUMBOS. Irradiation
      induced J-aggregation in [PEG786][NTf(2)] and to some extent in [PEG786][AOT]
      produced enhanced photostability. This observation was supported by use of both
      steady state and time-resolved fluorescence measurements.

PMID- 22957478
TI  - Towards a gendered perspective for Irish mental health policy and service
      provision.
AB  - BACKGROUND: The Irish Government has adopted "Gender Mainstreaming" as a strategy
      to promote equal opportunities between women and men in its National Development
      Plan. While current mental health policy addresses the principle of partnership
      and social inclusiveness as a way forward for mental health service provision, it
      still does not explicitly deal with the notion of gender and gender sensitivity.
      Indeed, Irish mental health policy and service provision is criticised for being
      gender-neutral. AIM: This paper explores the relationship between gender, mental
      health policy and service provision. METHOD: The literature on theoretical
      perspectives on mental health policy, gender and mental health in relation to
      Irish mental health policy is reviewed. RESULTS: The importance of gender for
      policy development and service provision is recognised, and the need to
      reformulate debate within a gendered context is discussed. Some key theoretical
      perspectives and their significance for mental health policy are considered with
      possible explanations for the absence of a gender perspective for Irish mental
      health policy presented. CONCLUSION: Arguably, a move towards developing gender
      sensitive mental health policy and service provision requires a stronger
      awareness of and connections between the macro, meso and micro levels for policy
      development and analysis.

PMID- 22957479
TI  - Providing quality care for the body and mind.

PMID- 22957480
TI  - I feel it in my bones: a rare presentation of idiopathic sclerosing orbital
      inflammation with hyperostosis.

PMID- 22957481
TI  - Diagnostic accuracy of electrophoretic analysis of native or defribrinated plasma
      using serum as a reference sample.
AB  - BACKGROUND: Electrophoretic analysis of plasma may provide inaccurate results
      unless plasma is defibrinated with ethanol. OBJECTIVE: The aim of this study,
      conducted following the Standards for Reporting of Diagnostic Accuracy (STARD),
      was to determine whether cellulose acetate (CAE), agarose gel (AGE), and
      capillary zone (CZE) electrophoresis of native plasma (NP) and defibrinated
      plasma (DP) provided the same information as serum electrophoretograms. METHODS:
      Serum, NP, and DP electrophoretograms obtained using the 3 methods were examined
      visually by 3 observers to identify changes in globulin fractions and provide
      diagnostic interpretations. Using serum analysis as the reference method,
      sensitivity, specificity, and positive likelihood ratio of NP and DP
      electrophoretograms to identify abnormal globulin profiles were calculated.
      RESULTS: Specimens from 46 dogs were analyzed. Albumin and alpha(1) - and gamma
      globulin fractions were lower and beta(2) -globulin fractions higher in NP than
      in serum and DP. Interpretations of NP electrophoretograms were the same as for
      serum in 54.8% (CAE), 51.2% (AGE), and 51.6% (CZE), revealed an increased beta
      globulin fraction in 32.3-41.5%, and resulted in misinterpretation, especially
      for CZE analysis, in 4.7-16.1% of the dogs; all dogs with abnormal serum
      electrophoretograms were identified correctly using NP. Analysis of DP was
      similar to serum analysis in about 2/3 of the dogs. In the others, defibrination
      did not resolve spurious plasma findings or induced additional changes. Up to 75
      and 27% of NP and DP electrophoretograms, respectively, were abnormal in dogs
      with normal serum electrophoretograms. Sensitivity for NP and DP analysis was
      high, but specificity for NP was poor. CONCLUSIONS: Analysis of NP provides the
      same information as serum analysis in > 50% of cases, and, despite low
      specificity, could preliminarily exclude the presence of abnormalities when only
      plasma is available. If electrophoretograms are not normalized by defibrination,
      electrophoretic abnormalities are likely present, and electrophoresis should be
      repeated using serum.

PMID- 22957482
TI  - Effect of L-arginine supplementation on blood pressure in pregnant women: a meta
      analysis of placebo-controlled trials.
AB  - OBJECTIVE: A meta-analysis of placebo-controlled trials was conducted to evaluate
      the effect of L-arginine supplementation on blood pressure (BP) in pregnancy.
      METHODS: Trials were searched in PubMed, Embase, and Cochrane Library. A total of
      five trials were included in the meta-analysis. RESULTS: L-arginine
      supplementation exhibited a mean decrease of 3.07 mmHg (p = 0.004) for diastolic
      blood pressure and a mean increase of 1.23 weeks (p = 0.002) for gestation age at
      delivery in pregnancy, but did not reduce systolic BP (p = 0.19) as compared to
      placebo. CONCLUSION: L-arginine supplementation had a significant effect of
      lowering diastolic blood pressure and prolonging gestation age in pregnancy.

PMID- 22957483
TI  - Prospective, randomized, double-blind, clinical evaluation of Aloe vera
      Barbadensis, applied in combination with a tongue protector to treat burning
      mouth syndrome.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of aloe vera (AV)
      applied in combination with a tongue protector, comparing this with a placebo.
      METHODS: A total of 75 patients with burning mouth syndrome (BMS) were divided
      into three groups randomly: Group I (tongue protector three times a day), Group
      II (tongue protector and 0.5 ml AV at 70% three times a day) and Group III
      (tongue protector and 0.5 ml placebo three times a day). Symptoms were evaluated
      by visual analogue scale (VAS), while patient psychological profiles were
      assessed using the Hospital Anxiety-Depression scale and their quality of life
      using the Oral Health Impact Profile 49 (OHIP-49). Treatment continued for 3
      months. RESULTS: Visual analogue scale pain values improved for all three study
      groups but without statistically significant differences between the groups (P =
      0.210). Regarding quality of life, no significant differences were found between
      groups with the exception of the OHIP-49 score for handicap. The overall clinical
      improvement was greater for Group II, with a difference almost reaching
      significance. CONCLUSIONS: The concomitant prescription of tongue protector and
      AV is effective for treating patients with BMS.

PMID- 22957484
TI  - Clinical testing for molecular targets for personalized treatment in lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. Over the past
      decades, the management of advanced stage lung cancer has been revolutionized
      from very limited options of systemic chemotherapy with limited efficacy to the
      present stage of testing for biomarkers (epidermal growth factor receptor (EGFR),
      gene mutations) to guide therapeutic decision and to improve efficacy of
      treatment. Relevant advancement in understanding of lung cancer biology also
      revealed that different lung tumours may carry different cancer driver gene
      mutations and thus adopt different carcinogenic pathways. These cancer driver
      gene mutations were found to be mutually exclusive in individual lung tumour
      further supporting the rationale of testing tumour sample for the presence of
      these mutations, especially when there could be corresponding specific agents
      against these molecular targets. The aim of this article is to review the current
      understanding of molecular targets that are important in the personalized therapy
      of lung cancer and how the testing for these molecular targets, namely EGFR, KRAS
      and ALK, will guide therapeutic decision in advanced stage lung cancer.

PMID- 22957486
TI  - Allergic contact dermatitis to methyl hydroxystearate in a rubber respirator.

PMID- 22957485
TI  - Mass rearing history and irradiation affect mating performance of the male fruit
      fly, Anastrepha obliqua.
AB  - As an initial step to improve the efficiency of the sterile insect technique
      applied to eradicate, suppress, and control wild Anastrepha obliqua (Macquart)
      (Diptera: Tephritidae) in mango producing areas of Mexico, the effect of
      radiation dose and mass rearing history on male mating performance was examined.
      Field cage tests in which both male and female laboratory flies were irradiated
      at different doses (0, 40, and 80 Gy) were released with cohorts of wild flies of
      both sexes, revealing that both mass rearing history and irradiation affected
      male mating performance. Laboratory males were accepted for copulation by wild
      females less frequently than wild males. Copulations involving laboratory males
      were shorter than those involving wild males. Irradiated males mated less
      frequently with wild females than wild males, and irradiated females appeared to
      be less able to reject courting males of both origins. High levels of fertility
      for untreated laboratory females crossed with males irradiated at different doses
      may reflect problems in mass rearing affecting homogeneity of pupal age before
      irradiation, and possibly masked a dose effect. Proposed remedial measures to
      improve male mating performance are discussed.

PMID- 22957487
TI  - Systemic allergic dermatitis of the lips resulting from allergy to an
      antimicrobial agent in a contact lens disinfecting solution.

PMID- 22957488
TI  - Allergic contact dermatitis caused by octocrylene in a young child.

PMID- 22957489
TI  - Allergic contact dermatitis caused by neem oil.

PMID- 22957490
TI  - A case of systemic allergic dermatitis caused by inhaled budesonide: cross
      reactivity in patch tests with the novel inhaled corticosteroid ciclesonide.

PMID- 22957491
TI  - Portal vein thrombosis - experience in a single centre.

PMID- 22957492
TI  - Pathway analysis of a genome-wide association study of ileal Crohn's disease.
AB  - The aim of this study was to identify the candidate single-nucleotide
      polymorphisms (SNPs) and candidate mechanisms of Crohn's disease (CD) and to
      generate a SNP to gene to pathway hypothesis using a pathway-based approach,
      ICSNPathway (Identify candidate Causal SNPs and Pathways) of genome-wide
      association studies (GWAS). An ileal CD GWAS dataset downloaded from NCBI dbGap
      was used in this study, which was conducted using 297,857 SNPs in 968 CD cases
      and 995 controls after quality control filtering. ICSNPathway analysis was
      applied to the CD GWAS dataset. ICSNPathway analysis identified seven candidate
      SNPs, nine pathways, which provided five hypothetical biological mechanisms.
      First, rs4077515 to caspase recruitment domain-containing protein 9 (CARD9) to
      response to peptidoglycan, positive regulation of tumor necrosis factor
      production, response to exogenous dsRNA, positive regulation of interleukin-6
      production, and positive regulation of innate immune response (nominal p<=0.002,
      false discovery rate [FDR]=0.027). Second, rs2066842, rs3135500, and rs5743291 to
      NOD2 to response to pepditoglycan, innate immune response activating signal
      transduction, and positive regulation of innate immune response (nominal
      p<=0.001, FDR=0.027). Third, rs8172678 to PPARGC1A to cellular glucose
      homeostasis (nominal p<0.001, FDR=0.031). Fourth, rs1050152 to SLC22A4 to
      cofactor transporter activity and vitamin transport (nominal p<0.001, FDR=0.044).
      Fifth, rs9621049 to TCN2 to vitamin transport (nominal p<0.001, FDR=0.046). In
      conclusion, by applying ICSNPathway analysis to CD GWAS, we identified candidate
      SNPs, genes involving CARD9, NOD2, PPARGC1A, SLC22A4, and TCN2, pathways, and
      hypothetical mechanisms, which may contribute to ileal CD susceptibility.

PMID- 22957493
TI  - Efficacy and safety during formulation switch of a pasteurized VWF/FVIII
      concentrate: results from an Italian prospective observational study in patients
      with von Willebrand disease.
AB  - Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the
      quantitative or qualitative deficiency of von Willebrand factor (VWF).
      Replacement therapy with plasma-derived VWF/factor VIII (FVIII) concentrates is
      required in patients unresponsive to desmopressin. To assess the efficacy, safety
      and ease of use of a new, volume-reduced (VR) formulation of VWF/FVIII
      concentrate Haemate((r)) P in patients requiring treatment for bleeding or
      prophylaxis for recurrent bleeding or for invasive procedures. Pharmacoeconomic
      variables were also recorded. Data were analysed using descriptive statistics.
      This was a multicentre, prospective, observational study. Consecutively enrolled
      patients received Haemate((r)) P VR according to their needs, and were followed
      for 24 months. Of the 121 patients enrolled, 25.6% had type 3 VWD and more than
      40% had severe disease. All patients were followed for 2 years, for a total of
      521 visits. On-demand treatment was given to 61.9% of patients, secondary long
      term prophylaxis to 25.6% and prophylaxis for surgery, dental or invasive
      procedures to 45.5%. The response to treatment was rated as good to excellent in
      >93-99% of interventions. The new formulation was well tolerated by all patients
      with no report of drug-related adverse events. The switch to volume-reduced
      Haemate((r)) P was easy to perform and infusion duration was decreased twofold
      compared with the previous formulation. Volume-reduced Haemate((r)) P was at
      least as effective and well-tolerated as the previous formulation.

PMID- 22957494
TI  - MicroRNAs miR-146a1, miR-155_2, and miR-200a1 are regulated in autoimmune thyroid
      diseases.

PMID- 22957495
TI  - Transcriptome analysis of long non-coding RNAs of the nucleus accumbens in
      cocaine-conditioned mice.
AB  - Cocaine dependence involves in the brain's reward circuit as well as nucleus
      accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies
      have documented altered expression of genes and identified transcription factor
      networks and epigenetic processes that are fundamental to cocaine addiction.
      However, all these investigations have focused on mRNA of encoding genes, which
      may not always reflect the involvement of long non-coding RNAs (lncRNAs), which
      has been implied in a broad range of biological processes and complex diseases
      including brain development and neuropathological process. To explore the
      potential involvement of lncRNAs in drug addiction, which is viewed as a form of
      aberrant neuroplasticity, we used a custom-designed microarray to examine the
      expression profiles of mRNAs and lncRNAs in brain NAc of cocaine-conditioned mice
      and identified 764 mRNAs, and 603 lncRNAs were differentially expressed.
      Candidate lncRNAs were identified for further genomic context characterization as
      sense-overlap, antisense-overlap, intergenic, bidirection, and ultra-conserved
      region encoding lncRNAs. We found that 410 candidate lncRNAs which have been
      reported to act in cis or trans to their targeted loci, providing 48 pair mRNA
      lncRNAs. These results suggest that the modification of mRNAs expression by
      cocaine may be associated with the actions of lncRNAs. Taken together, our
      results show that cocaine can cause the genome-wide alterations of lncRNAs
      expressed in NAc, and some of these modified RNA transcripts may to play a role
      in cocaine-induced neural plasticity and addiction.

PMID- 22957496
TI  - Presence of anti-ADAMTS13 antibodies in obesity.
AB  - BACKGROUND: The low-grade chronic inflammation present in obesity has been
      recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular
      complications. In this context, production by adipose organ of a number of
      inflammatory adipokines could play a crucial role. It has been reported that
      obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura
      (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13
      antibodies, but the pathophysiological link between obesity and TTP is still
      unknown. We aimed to investigate mechanisms linking obesity to risk of TTP.
      MATERIALS AND METHODS: Eighty obese patients consecutively admitted to Bariatric
      Unit of Padua between 2006 and 2009, and 39 lean subjects were characterized by
      anthropometric, metabolic and inflammatory parameters. ADAMTS13 autoantibodies,
      activity and antigen levels, and several cytokines including thrombospondin-1
      were measured. RESULTS: 21.3% of obese patients were positive for noninhibitory
      ADAMTS13 autoantibodies, while all lean subjects were negative (P<0.01). No
      differences in ADAMTS13 activity and antigen levels were found. Thrombospondin-1
      levels were significantly higher in obese than in lean subjects (974.4 +/- 592.7
      vs. 318.9 +/- 202.1 ng/mL; P<0.001) and were inversely correlated with ADAMTS13
      activity (R=-0.4853; P<0.001). Dot blot suggests that anti-ADAMTS13 antibodies in
      obese patients bind recombinant thrombospondin-1. CONCLUSIONS: We suggest that
      anti-ADAMTS13 antibodies are directed against thrombospondin domains shared
      between ADAMTS13 and thrombospondin-1 and that their generation may be sustained
      by high levels of thrombospondin-1. This phenomenon could be of relevance,
      because little is known on the pathogenesis of TTP and its possible link with
      obesity.

PMID- 22957497
TI  - Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in
      pathological N0 squamous cell carcinoma of the tongue.
AB  - AIMS: Cancer cells induce de-novo lymphatic vessel growth within draining lymph
      nodes before they metastasize. The aim of this study was to retrospectively
      evaluate lymph node lymphangiogenesis before the establishment of nodal
      recurrence in squamous cell carcinoma (SCC) of the tongue. METHODS AND RESULTS:
      Surgical specimens from 28 patients with pT2-T3N0M0 SCC of the tongue after local
      excision with supraomohyoid neck dissection were studied by immunohistochemistry.
      Intranodal lymphatic endothelium was highlighted by podoplanin staining to
      evaluate lymphatic vessel counts (LVCs). Primary tumour sections were examined
      for the expression of lymphangiogenic factors: vascular endothelial growth factor
      (VEGF)-C and VEGF-D. LVCs in regional lymph nodes were significantly increased in
      the cases with nodal recurrence (P=0.0013). Simultaneous increases in VEGF-C and
      VEGF-D expression were significantly associated with both an increase in LVC in
      regional lymph nodes (P=0.0001) and a decrease in the rate of survival without
      nodal recurrence (P=0.016). CONCLUSIONS: Knowing the status of lymphangiogenesis
      in the regional pN0 lymph nodes in tongue cancer would help in predicting which
      patients will develop nodal recurrence. The use of a therapeutic approach which
      blocks lymphangiogenic factors, such as VEGF-C and VEGF-D, may be beneficial in
      suppressing the lymphatic spread of tongue cancer with intense intranodal
      lymphangiogenesis.

PMID- 22957498
TI  - Update on the role of systemic vitamin D in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory type of eczema. The
      underlying cause of AD has not been established. Several studies have shown
      initial epidermal barrier dysfunction with subsequent immune activation as the
      underlying mechanism. Recently, in addition to its classical role in calcium
      homeostasis, vitamin D has been recognized for its effect on immunomodulation.
      Animal studies, case reports, and randomized clinical trials have suggested that
      vitamin D, through various mechanisms, may alleviate the symptoms of AD. The
      majority of these studies indicate an inverse relationship between the severity
      of atopic dermatitis and vitamin D levels. Furthermore, studies have shown that,
      in individuals with AD who are deficient in vitamin D, repletion of vitamin D
      results in decreased severity of disease. We present a review of the present
      literature that suggests a potentially significant role for vitamin D in the
      treatment of AD.

PMID- 22957499
TI  - Experiences of providing prosthetic and orthotic services in Sierra Leone--the
      local staff's perspective.
AB  - In Sierra Leone, West Africa, there are many people with disabilities in need of
      rehabilitation services after a long civil war. PURPOSE: The aim of this
      qualitative study was to explore the experiences of prosthetic and orthotic
      service delivery in Sierra Leone from the local staff's perspective. METHOD:
      Fifteen prosthetic and orthotic technicians working at all the rehabilitation
      centres providing prosthetic and orthotic services in Sierra Leone were
      interviewed. The interviews were transcribed and subjected to latent content
      analysis. RESULTS: One main theme emerged: sense of inability to deliver high
      quality prosthetic and orthotic services. This main theme was generated from
      eight sub-themes: Desire for professional development; appraisals of work
      satisfaction and norms; patients neglected by family; limited access to the
      prosthetic and orthotic services available; problems with materials and machines;
      low public awareness concerning disabilities; marginalisation in society and low
      priority on the part of government. CONCLUSIONS: The findings illustrated
      traditional beliefs about the causes of disability and that the public's attitude
      needs to change to include and value people with disabilities. Support from
      international organisations was considered necessary as well as educating more
      prosthetic and orthotic staff to a higher level.

PMID- 22957501
TI  - Pilot study of remote telemonitoring in COPD.
AB  - BACKGROUND: Remote in-home monitoring (RM) of symptoms and physiological
      variables may allow early detection and treatment of exacerbations of chronic
      obstructive pulmonary disease (COPD). It is unclear whether RM improves patient
      outcomes or healthcare resource utilization. This study determined whether RM is
      feasible in patients with COPD and if RM reduces hospital admissions or length of
      stay (LOS) or improves health-related quality of life (HRQOL). SUBJECTS AND
      METHODS: Forty-four patients were randomized to standard best practice care (SBP)
      (n=22) or SBP+RM (n=22). RM involved daily recording of physiological variables,
      symptoms, and medication usage. RESULTS: There were no differences (mean+/-SD,
      SBP versus SBP+RM) in age (68+/-8 versus 70+/-9 years), gender (male:female 10:12
      in both groups), or previous computer familiarity (59% versus 50%) between
      groups. The SBP group had a lower forced expiratory volume in 1 s (0.66+/-0.24
      versus 0.91+/-0.34 L, p<0.01) and more current smokers (six versus none, p<0.05).
      There were no differences in number of COPD-related admissions/year (1.5+/-1.8
      versus 1.3+/-1.7, p=0.76), COPD-related LOS days/year (15.6+/-19.4 versus 11.4+/
      19.6, p=0.66), total admissions/year (2.2+/-2.1 versus 2.0+/-2.3, p=0.86), total
      LOS days/year (22.1+/-29.9 versus 21.6+/-30.4, p=0.88), or HRQOL between the two
      groups. CONCLUSIONS: The addition of RM to SBP was feasible but did not reduce
      healthcare utilization or improve quality of life in this group of patients
      already receiving comprehensive respiratory care.

PMID- 22957502
TI  - Conceptual framework for development of comprehensive e-health evaluation tool.
AB  - OBJECTIVE: The main objective of this study was to develop an e-health evaluation
      tool based on a conceptual framework including relevant theories for evaluating
      use of technology in health programs. This article presents the development of an
      evaluation framework for e-health programs. MATERIALS AND METHODS: The study was
      divided into three stages: Stage 1 involved a detailed literature search of
      different theories and concepts on evaluation of e-health, Stage 2 plotted e
      health theories to identify relevant themes, and Stage 3 developed a matrix of
      evaluation themes and stages of e-health programs. RESULTS: The framework
      identifies and defines different stages of e-health programs and then applies
      evaluation theories to each of these stages for development of the evaluation
      tool. This framework builds on existing theories of health and technology
      evaluation and presents a conceptual framework for developing an e-health
      evaluation tool to examine and measure different factors that play a definite
      role in the success of e-health programs. The framework on the horizontal axis
      divides e-health into different stages of program implementation, while the
      vertical axis identifies different themes and areas of consideration for e-health
      evaluation. CONCLUSIONS: The framework helps understand various aspects of e
      health programs and their impact that require evaluation at different stages of
      the life cycle. The study led to the development of a new and comprehensive e
      health evaluation tool, named the Khoja-Durrani-Scott Framework for e-Health
      Evaluation.

PMID- 22957503
TI  - Using nursing expertise and telemedicine to increase nursing collaboration and
      improve patient outcomes.
AB  - OBJECTIVE: To examine the impact of the first nurse-implemented tele-intensive
      care unit (tele-ICU) staffing model, with the intent that shared nursing
      vigilance and collaboration can decrease patient complications potentially
      impacting patient outcomes. SUBJECTS AND MATERIALS: A quantitative study used a
      pre-post program design of 90 staff nurses in the Adult Critical Care Unit, 10
      tele-ICU nurses, and 1,308 patient participants at Providence Alaska Medical
      Center (Anchorage, AK). Twelve months of baseline data were collected: Acute
      Physiology and Chronic Health Evaluation severity-adjusted ICU length of stay
      (LOS), ICU mortality, protocols for the prevention of ventilator-associated
      pneumonia (VAP), ventilator bundle compliance (stress ulcer and venous thrombosis
      prophylaxis), and glucose control. Follow-up data were obtained using the same
      outcomes examined for baseline: 9 months for the nurse and only an additional 3
      months with the addition of physician monitoring services. RESULTS: Data
      demonstrated post-tele-ICU implementation improvements as follows: severity
      adjusted LOS decrease, 15% (222 patient-days saved); severity-adjusted ICU
      mortality decrease, 14% (20 lives saved); compliance improvement of "at-risk"
      patients, restraint documentation 26% improvement; ventilator bundle compliance,
      6% increase; and VAP, 13% decrease in patient-days. CONCLUSIONS: Collaboration
      between bedside and remote nurses in conjunction with the use of tele-ICU program
      technology positively impacts critical care patient outcomes. Effective nursing
      collaboration and communication and improved patient outcomes can be attained
      through nursing vigilance and attention to best practices or health system
      protocols and the use of smart technology such as the population management tools
      in the tele-ICU program.

PMID- 22957504
TI  - Circulating lymphangiogenic factors in preeclampsia.
AB  - BACKGROUND: Preeclampsia (PE), a human pregnancy-specific disorder is
      characterized by an anti-angiogenic state due to high levels of circulating
      soluble vascular endothelial growth factor 1 (sVEGFR-1). However, the role of
      lymphangiogenesis in PE has not been investigated. Recently, impaired vascular
      endothelial growth factor C (VEGF-C) (factor that regulates lymphangiogenesis)
      signaling has been implicated in the pathogenesis of interstitial edema and salt
      sensitive hypertension. Therefore, we hypothesized that circulating VEGF-C and
      its circulating receptors (sVEGFR-2 and sVEGFR-3) may also be altered in PE and
      correlate with the severity of the phenotype. METHODS: We analyzed plasma levels
      of VEGF-C, sVEGFR-1, sVEGFR-2, and sVEGFR-3 in women with gestational
      hypertension (GHTN, n = 20), PE (n = 20), and normotensive pregnancies (NP, n =
      20) in the third trimester and values were reported as mean +/- SD in pg/mL.
      RESULTS: As previously reported, sVEGFR-1 levels were significantly higher in
      subjects with PE (19,938 +/- 12,973) than in GHTN (7156 +/- 5432), p < 0.01 or NP
      (7760 +/- 6018), p < 0.01. VEGF-C levels were lower in subjects with GHTN (676 +/
      323) than in PE (1335 +/- 625), p < 0.01, but not statistically different than
      in NP (971 +/- 556), p = 0.11. There was a trend toward lower sVEGFR-2 in PE as
      compared to GHTN or NP. Interestingly, sVEGFR-3 was significantly lower in PE
      (54,371 +/- 21,107) as compared to NP (83,709 +/- 24,983), p < 0.01, but not
      different as compared to GHTN (54,642 +/- 26,947). The ratio of sVEGFR-2 + sVEGFR
      3/VEGF-C was dramatically lower during PE (57 +/- 38) as compared to GHTN (113 +/
      72), p < 0.01 or NP (133 +/- 91), p < 0.01. CONCLUSIONS: PE is characterized by
      circulating pro-lymphangiogenic state as evidenced by decreased sVEGFR-3,
      slightly decreased sVEGFR-2, increased VEGF-C, and a dramatically lower ratio of
      sVEGFR-2 + sVEGFR-3/VEGF-C. Our data suggest that the circulating pro
      lymphangiogenic state during PE may be a compensatory response to edema and
      hypertension. Additional studies are needed to evaluate the clinical relevance of
      the altered lymphangiogenic signaling pathway during PE.

PMID- 22957505
TI  - Gene expression profiling in the thiamethoxam resistant and susceptible B-biotype
      sweetpotato whitefly, Bemisia tabaci.
AB  - Thiamethoxam has been used as a major insecticide to control the B-biotype
      sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Due to
      its excessive use, a high level of resistance to thiamethoxam has developed
      worldwide over the past several years. To better understand the molecular
      mechanisms underlying this resistance in B. tabaci, gene profiles between the
      thiamethoxam-resistant and thiamethoxam-susceptible strains were investigated
      using the suppression subtractive hybridization (SSH) library approach. A total
      of 72 and 52 upand down-regulated genes were obtained from the forward and
      reverse SSH libraries, respectively. These expressed sequence tags (ESTs) belong
      to several functional categories based on their gene ontology annotation. Some
      categories such as cell communication, response to abiotic stimulus, lipid
      particle, and nuclear envelope were identified only in the forward library of
      thiamethoxam-resistant strains. In contrast, categories such as behavior, cell
      proliferation, nutrient reservoir activity, sequence-specific DNA binding
      transcription factor activity, and signal transducer activity were identified
      solely in the reverse library. To study the validity of the SSH method, 16
      differentially expressed genes from both forward and reverse SSH libraries were
      selected randomly for further analyses using quantitative realtime PCR (qRT-PCR).
      The qRT-PCR results were fairly consistent with the SSH results; however, only
      50% of the genes showed significantly different expression profiles between the
      thiamethoxam-resistant and thiamethoxam-susceptible whiteflies. Among these
      genes, a putative NAD-dependent methanol dehydrogenase was substantially over
      expressed in the thiamethoxamresistant adults compared to their susceptible
      counterparts. The distributed profiles show that it was highly expressed during
      the egg stage, and was most abundant in the abdomen of adult females.

PMID- 22957506
TI  - Developing an educational research framework for evaluating rural training of
      health professionals: a case for innovation.
AB  - BACKGROUND: World-wide, rural clinical training of undergraduate medical students
      is looking to transform learning experiences, calling for the adoption of
      innovative approaches that create spaces for curriculum renewal and new ways of
      thinking. In order for these teaching models to gain acceptance and credibility
      among the relevant academic communities, it is critical that they be studied and
      evaluated. AIM: This article describes an innovative rural education intervention
      and a concomitant, intentional process that was adopted to establish a research
      framework within which the intervention will be evaluated. METHODS: Key role
      players participated in a one-day workshop aimed at developing the framework. A
      collaborative, structured process that moved through three phases of deliberation
      and reflection was followed. RESULTS: The documentation and raw data generated
      during the workshop was used to generate the framework that will serve as a
      blueprint for ensuring the study and evaluation of the educational innovation.
      CONCLUSION: Establishing an educational research framework, by adopting a
      consultative and collaborative process, provides a vehicle for encouraging a
      culture of critical accountability that seeks to discern evidence of good
      practice in the training of health care workers in a rural context.

PMID- 22957507
TI  - Beyond the ward and waiting room: a community-based non-clinical placement
      programme for Australian medical students.
AB  - BACKGROUND: Placement programmes are essential to medical education but almost
      invariably take place in clinical settings, even when community based.
      Australia's Monash University, however, has included in its core MBBS curriculum
      a non-clinical placement for second-year students, the Community Based Practice
      (CBP) programme. This involves partnerships with community organisations that are
      mostly non-medical. The programme includes a health promotion (HP) component
      where students respond to a HP or support need nominated by their placement
      organisation. Though inspired by community-based medical education (CBME)
      programmes in England and South Australia's Flinders University, its non-clinical
      focus represents a creative development in Australian medical education. METHODS:
      This article describes the programme, explores its place within CBME and outlines
      the results of its analysis of student responses using SPSS and NVivo. RESULTS:
      The evidence showed development of students' communication skills; increased
      understanding and appreciation of the mainly non-medical health support
      infrastructure in local communities; increased understanding of HP and community
      health support at the local level; and contributions to the placement
      organisations through small-scale research or health support projects.
      CONCLUSION: Placement programmes such as this can significantly contribute to
      medical education, especially in supporting health in local communities and
      understanding the needs of the marginalised.

PMID- 22957508
TI  - The case of the entitled resident: a composite case study of a resident
      performance problem syndrome with interdisciplinary commentary.
AB  - BACKGROUND: Residents with performance problems create substantial burden on
      programs and institutions. Understanding the nature and quality of performance
      problems can help in learning to address performance problems. AIM: We sought to
      illuminate the effects of resident performance problems and the potential
      solutions for those problems from the perspectives of people with various roles
      in health care. METHODS: We created a composite portrait from several residents
      who demonstrated a cluster of common performance characteristics and whose
      chronic or serious maladaptive behavior and response to situations created
      problems for themselves, for their clinical colleagues, and for faculty of their
      residency program. The composite was derived from in-depth interviews of program
      directors and review of resident records. We solicited practitioners from
      multiple fields to respond to the portrait by answering a series of questions
      about severity, prognosis, and how and whether one could reliably remediate a
      person with these performance characteristics. We present their perspectives in a
      manner borrowed from the New England Journal of Medicine's "Case Records of the
      Massachusetts General Hospital." RESULTS: We created a composite portrait of a
      resident whose behavior suggested he felt entitled to benefits his peers were not
      entitled to. Experts reflecting on his behavior varied in their opinion about the
      effect the resident would have on the health care system. They suggested
      approaches to remediation that required substantial time and effort from the
      faculty. CONCLUSION: Programs must balance the needs of individual residents to
      adjust their behaviors with the needs of the health care system and other people
      within it.

PMID- 22957510
TI  - Oxygen reduction electrocatalyst based on strongly coupled cobalt oxide
      nanocrystals and carbon nanotubes.
AB  - Electrocatalyst for oxygen reduction reaction (ORR) is crucial for a variety of
      renewable energy applications and energy-intensive industries. The design and
      synthesis of highly active ORR catalysts with strong durability at low cost is
      extremely desirable but remains challenging. Here, we used a simple two-step
      method to synthesize cobalt oxide/carbon nanotube (CNT) strongly coupled hybrid
      as efficient ORR catalyst by directly growing nanocrystals on oxidized
      multiwalled CNTs. The mildly oxidized CNTs provided functional groups on the
      outer walls to nucleate and anchor nanocrystals, while retaining intact inner
      walls for highly conducting network. Cobalt oxide was in the form of CoO due to a
      gas-phase annealing step in NH(3). The resulting CoO/nitrogen-doped CNT (NCNT)
      hybrid showed high ORR current density that outperformed Co(3)O(4)/graphene
      hybrid and commercial Pt/C catalyst at medium overpotential, mainly through a 4e
      reduction pathway. The metal oxide/carbon nanotube hybrid was found to be
      advantageous over the graphene counterpart in terms of active sites and charge
      transport. Last, the CoO/NCNT hybrid showed high ORR activity and stability under
      a highly corrosive condition of 10 M NaOH at 80  degrees C, demonstrating the
      potential of strongly coupled inorganic/nanocarbon hybrid as a novel catalyst
      system in oxygen depolarized cathode for chlor-alkali electrolysis.

PMID- 22957511
TI  - Pd/Cu-catalyzed C-H arylation of 1,3,4-thiadiazoles with (hetero)aryl iodides,
      bromides, and triflates.
AB  - The direct C-H arylation of 1,3,4-thiadiazoles with a wide range of (hetero)aryl
      iodides, bromides, and triflates is described using a Pd/Cu-catalyzed protocol.
      The methodology is compatible with substrates possessing electron-donating or
      electron-withdrawing substituents and also tolerates sterically hindered aryl
      halides. The utility of the developed protocol is demonstrated by a one-pot C-H
      arylation-Suzuki coupling sequence.

PMID- 22957512
TI  - Explosion of ophthalmic collaborative research networks in Australia.

PMID- 22957514
TI  - Acid-dependent degradation of a [2Fe-2S] cluster by nitric oxide.
AB  - New types of degradation products of iron-sulfur clusters by nitric oxide (NO)
      have been identified in the acidic environment. In the absence of acid, NO reacts
      with (Et(4)N)(2)[Fe(2)S(2)Cl(4)] (1) to form a {Fe(NO)(2)}(9) dinitrosyliron
      complex, (Et(4)N)[Fe(NO)(2)Cl(2)] (2), wherein the bridging sulfides are oxidized
      to elemental sulfur by four electrons (2S(2-) -> 2S(0) + 4e(-)). In contrast, the
      successive additions of NO and HCl to 1 result in the formation of a {Fe(NO)}(7)
      mononitrosyliron complex, (Et(4)N)[Fe(NO)Cl(3)] (3), along with elemental sulfur
      and hydrogen sulfide (H(2)S), which are the two-electron-oxidized products of the
      bridging sulfides (2S(2-) + 2H(+) -> H(2)S + S(0) + 2e(-)). The results
      demonstrate that the acidic environment plays a significant role in controlling
      the chemistry of an iron-sulfur cluster with NO and imply how two important
      gaseous molecules, NO and H(2)S, can be interconnected through iron-sulfur
      clusters.

PMID- 22957513
TI  - Oligothiol graft-copolymer coatings stabilize gold nanoparticles against harsh
      experimental conditions.
AB  - We report that poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) copolymers
      that bear multiple thiol groups on the polymer backbone are exceptional ligands
      for gold nanoparticles (AuNPs). In general, these graft copolymer ligands
      stabilize AuNPs against environments that would ordinarily lead to particle
      aggregation. To characterize the effect of copolymer structure on AuNP stability,
      we synthesized thiolated PLL-g-PEGs (PLL-g-[PEG:SH]) with different backbone
      lengths, PEG grafting densities, and number of thiols per polymer chain. AuNPs
      were then combined with these polymer ligands, and the stabilities of the
      resulting AuNP@PLL-g-[PEG:SH] particles against high temperature, oxidants, and
      competing thiol ligands were characterized using dynamic light scattering,
      visible absorption spectroscopy, and fluorescence spectrophotometry. Our
      observations indicate that thiolated PLL-g-PEG ligands combine thermodynamic
      stabilization via multiple Au-S bonds and steric stabilization by PEG grafts, and
      the best graft copolymer ligands balance these two effects. We hope that this new
      ligand system enables AuNPs to be applied to biotechnological applications that
      require harsh experimental conditions.

PMID- 22957516
TI  - An update on vaccines for tuberculosis - there is more to it than just waning of
      BCG efficacy with time.
AB  - INTRODUCTION: Apart from better diagnostics and new anti-microbial drugs, an
      effective vaccine for tuberculosis is urgently needed to halt this poverty
      related disease, afflicting millions of people worldwide. AREAS COVERED: After a
      general introduction on the global threat of tuberculosis, the pros and cons of
      the existing M. bovis BCG vaccine are discussed. As the correlates of protection
      against tuberculosis remain largely unknown, new findings in biomarker research
      are described. Next, an update on the ongoing Phase I and Phase II clinical
      trials is given. Finally, some of the most promising novel pre-clinical
      developments using live attenuated vaccines, sub-unit vaccines, prime-boost
      strategies, and new vaccination routes are discussed. The field has made
      considerable progress and 12 vaccine candidates have now actually entered Phase I
      or Phase IIa and IIb clinical trials. EXPERT OPINION: It is argued that the
      variable protection conferred by the existing BCG vaccine against reactivation of
      latent TB is caused not only by waning of its efficacy with time but also by its
      weak induction of MHC class I restricted responses. Prime-boost strategies based
      on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use
      of plasmid DNA vaccination might offer a solution.

PMID- 22957517
TI  - Abstracts of the British Association for Cytopathology Scientific Conference and
      Trade Exhibition 2012. September 13-15, 2012. Keele, United Kingdom.

PMID- 22957518
TI  - Actinide chelation: biodistribution and in vivo complex stability of the targeted
      metal ions.
AB  - Because of the continuing use of nuclear fuel sources and heightened threats of
      nuclear weapon use, the amount of produced and released radionuclides is
      increasing daily, as is the risk of larger human exposure to fission product
      actinides. A rodent model was used to follow the in vivo distribution of
      representative actinides, administered as free metal ions or complexed with
      chelating agents including diethylenetriamine pentaacetic acid (DTPA) and the
      hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Different
      metabolic pathways for the different metal ions were evidenced, resulting in
      intricate ligand- and metal-dependent decorporation mechanisms. While the three
      studied chelators are known for their unrivaled actinide decorporation
      efficiency, the corresponding metal complexes may undergo in vivo decomposition
      and release metal ions in various biological pools. This study sets the basis to
      further explore the metabolism and in vivo coordination properties of
      internalized actinides for the future development of viable therapeutic chelating
      agents.

PMID- 22957519
TI  - HPLC-PDA-MS and NMR characterization of a hydroalcoholic extract of Citrus
      aurantium L. var. amara peel with antiedematogenic activity.
AB  - The phytochemical profile of a hydroalcoholic extract of Citrus aurantium var.
      amara L. peel, used as herbal medicine, was characterized by HPLC-PDA-MS. Two di
      C-glycosyl flavones (vincenin II and diosmetin 6,8-di-C-glucoside), a series of
      flavones (luteolin 7-O-neohesperidoside, rhoifolin, and neodiosmin), and
      flavanone (neoeriocitrin, naringin, and neohesperidin) 7-O-neohesperidosides and
      two methoxyflavones (nobiletin and tangeretin), commonly present in Citrus, were
      identified. Furthermore, brutieridin and melitidin, two 3-hydroxy-3
      methylglutaryl flavanone glycosides, were also characterized along with rhoifolin
      4'-glucoside and three coumarins (8,3'-beta-D-glucopyranosyloxy-2'-hydroxy-3'
      methylbutyl-7-methoxycoumarin, merazin hydrate, and isomerazin). A preparative
      isolation procedure followed by NMR spectroscopy confirmed the proposed
      structures of the major flavonoids and identified the coumarins. The phenolic
      content was found to be 14.8 mg mL(-1), and naringin and neohesperidin were the
      compounds present in the highest concentration (3.6 and 2.6 mg mL(-1)). The
      extract of C. aurantium peel inhibited significantly (p < 0.05) both histamine-
      and dextran-induced edema in rats in a concentration-dependent manner (IC(50) =
      119.6 and 118.3 mg kg(-1), respectively), providing evidence for the therapeutic
      use of C. aurantium var. amara peel.

PMID- 22957520
TI  - Women's perception of future risk following pregnancies complicated by
      preeclampsia.
AB  - OBJECTIVE: To elicit women's personal understanding of future cardiovascular
      risk, following a pregnancy complicated by preeclampsia, and to identify the
      postnatal needs of these women. METHODS: Semi-structured interviews with 12 women
      with a recent history of preeclampsia who had attended a postnatal follow-up
      clinic. RESULTS: The interviews were held at a median of 47 weeks postpartum
      (range 24-62 weeks). Family history of cardiovascular disease was associated with
      a greater awareness of future cardiovascular risk. Women without traditional risk
      factors found it hard to envisage themselves as being at risk and may not see the
      relevance of such information. It may take several months after delivery for a
      woman to be able to fully consider her own health as well as the baby's; a
      reminder of risk and health information is needed. CONCLUSIONS: Although
      receptive to follow-up, the situational factors of being a new mother need to be
      taken into account to engage successfully with this patient group. Further
      research is needed to help clarify the extent to which a history of preeclampsia
      is an independent factor for future cardiovascular disease to provide a solid
      foundation for effective risk communication.

PMID- 22957522
TI  - Glucose in the ICU--evidence, guidelines, and outcomes.

PMID- 22957523
TI  - Aneurysm geometry.

PMID- 22957521
TI  - Tight glycemic control versus standard care after pediatric cardiac surgery.
AB  - BACKGROUND: In some studies, tight glycemic control with insulin improved
      outcomes in adults undergoing cardiac surgery, but these benefits are unproven in
      critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the
      hypothesis that tight glycemic control reduces morbidity after pediatric cardiac
      surgery. METHODS: In this two-center, prospective, randomized trial, we enrolled
      980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary
      bypass. Patients were randomly assigned to either tight glycemic control (with
      the use of an insulin-dosing algorithm targeting a blood glucose level of 80 to
      110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac
      intensive care unit (ICU). Continuous glucose monitoring was used to guide the
      frequency of blood glucose measurement and to detect impending hypoglycemia. The
      primary outcome was the rate of health care-associated infections in the cardiac
      ICU. Secondary outcomes included mortality, length of stay, organ failure, and
      hypoglycemia. RESULTS: A total of 444 of the 490 children assigned to tight
      glycemic control (91%) received insulin versus 9 of 490 children assigned to
      standard care (2%). Although normoglycemia was achieved earlier with tight
      glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was
      maintained for a greater proportion of the critical illness period (50% vs. 33%,
      P<0.001), tight glycemic control was not associated with a significantly
      decreased rate of health care-associated infections (8.6 vs. 9.9 per 1000 patient
      days, P=0.67). Secondary outcomes did not differ significantly between groups,
      and tight glycemic control did not benefit high-risk subgroups. Only 3% of the
      patients assigned to tight glycemic control had severe hypoglycemia (blood
      glucose <40 mg per deciliter [2.2 mmol per liter]). CONCLUSIONS: Tight glycemic
      control can be achieved with a low hypoglycemia rate after cardiac surgery in
      children, but it does not significantly change the infection rate, mortality,
      length of stay, or measures of organ failure, as compared with standard care.
      (Funded by the National Heart, Lung, and Blood Institute and others; SPECS
      ClinicalTrials.gov number, NCT00443599.).

PMID- 22957524
TI  - Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience
      from the Mayo Clinic.
AB  - OBJECT: Gangliogliomas comprise less than 1% of all brain tumors and occur most
      often in children. Therefore, there are a limited number of patients and data
      involving the use or role of adjuvant therapy after subtotal resections (STRs) of
      gangliogliomas. The objective of this study was to examine and review the Mayo
      Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of
      recurrence, and the role of radiation therapy after STR or only biopsy. METHODS:
      Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were
      reviewed. Data on clinical outcomes and therapy received were analyzed. The
      Kaplan-Meier method was used to estimate progression-free survival (PFS) and
      overall survival. RESULTS: The median age at diagnosis was 19 years. The median
      potential follow-up as of June 2008 was 142 months (range 9-416 months). Fifteen
      year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate
      of 37%. Progression-free survival was dramatically affected by extent of initial
      resection (p < 0.0001). CONCLUSIONS: This single-institution retrospective series
      of patients with gangliogliomas is unique given its large cohort size with a long
      follow-up duration, and confirms the excellent long-term survival rate in this
      group. The study also shows the importance of resection extent on likelihood of
      recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have
      poor PFS. Radiation therapy may delay time to progression in patients with
      unresectable disease.

PMID- 22957525
TI  - Short circuit in deep brain stimulation.
AB  - OBJECT: The authors undertook this study to investigate the incidence, cause, and
      clinical influence of short circuits in patients treated with deep brain
      stimulation (DBS). METHODS: After the incidental identification of a short
      circuit during routine follow-up, the authors initiated a policy at their
      institution of routinely evaluating both therapeutic impedance and system
      impendence at every outpatient DBS follow-up visit, irrespective of the presence
      of symptoms suggesting possible system malfunction. This study represents a
      report of their findings after 1 year of this policy. RESULTS: Implanted DBS
      leads exhibiting short circuits were identified in 7 patients (8.9% of the
      patients seen for outpatient follow-up examinations during the 12-month study
      period). The mean duration from DBS lead implantation to the discovery of the
      short circuit was 64.7 months. The symptoms revealing short circuits included the
      wearing off of therapeutic effect, apraxia of eyelid opening, or dysarthria in 6
      patients with Parkinson disease (PD), and dystonia deterioration in 1 patient
      with generalized dystonia. All DBS leads with short circuits had been anchored to
      the cranium using titanium miniplates. Altering electrode settings resulted in
      clinical improvement in the 2 PD cases in which patients had specific symptoms of
      short circuits (2.5%) but not in the other 4 cases. The patient with dystonia
      underwent repositioning and replacement of a lead because the previous lead was
      located too anteriorly, but did not experience symptom improvement. CONCLUSIONS:
      In contrast to the sudden loss of clinical efficacy of DBS caused by an open
      circuit, short circuits may arise due to a gradual decrease in impedance, causing
      the insidious development of neurological symptoms via limited or extended
      potential fields as well as shortened battery longevity. The incidence of short
      circuits in DBS may be higher than previously thought, especially in cases in
      which DBS leads are anchored with miniplates. The circuit impedance of DBS should
      be routinely checked, even after a long history of DBS therapy, especially in
      cases of miniplate anchoring.

PMID- 22957526
TI  - Influence of the combination of patient age and deep venous drainage on brain
      arteriovenous malformation recurrence after surgery.
AB  - OBJECT: Case reports suggest that young age is a critical factor in determining
      recurrence of brain arteriovenous malformations (AVMs) after surgery. However,
      other factors that may contribute to the increased risk of recurrence have not
      been considered. In this study, the authors' goal was to ascertain the risk and
      risk factors of recurrence after resection of AVMs of the brain. METHODS: A
      consecutive case series (prospectively collected data) of 600 cases of resection
      of brain AVMs was retrospectively analyzed. Radiological evidence of recurrence
      or nonrecurrence, as well as clinical evidence of recurrence, could be
      established in 427 of these cases that underwent follow-up for more than 350 days
      after initial surgery. These cases were analyzed using Kaplan-Meier curves and
      Cox regression with respect to age and the presence of deep venous drainage.
      RESULTS: Nine recurrent AVMs were found in 8 patients. By analysis of the Kaplan
      Meier curves, the 10-year recurrence rate was 14% for those with deep venous
      drainage, compared with 4% for those without deep venous drainage. Stratifying by
      age, in the 0- to 20-year age group, the 10-year recurrence rates were 63% and
      13% for those with and without deep venous drainage, respectively. In the 20- to
      39-year age group, the rates were 5% and 0% respectively, and in the 40-year and
      older age group they were 0% and 3%, respectively. The hazard ratio for deep
      venous drainage, adjusted for age, was 5.97 (95% CI 1.20-29.69, p = 0.029).
      CONCLUSIONS: The risk of recurrence after AVM resection is significant for young
      patients with deep venous drainage.

PMID- 22957527
TI  - Reliability of postoperative photographs in assessment of facial nerve function
      after vestibular schwannoma resection.
AB  - OBJECT: This study was undertaken to assess the reliability of observations of
      postoperative photographs in assigning House-Brackmann scores as outcome measures
      for patients following resection of vestibular schwannomas. METHODS: Forty
      pictures of differing facial expressions typically elicited from patients for
      assigning House-Brackmann scores were individually evaluated by neurosurgery
      residents and faculty members at the University of Alabama at Birmingham; a score
      was assigned to each picture by the individual raters. The interrater reliability
      was measured using the Spearman correlation coefficient, Kendall coefficient of
      concordance, and kappa statistic; internal consistency was calculated using the
      Cronbach alpha reliability estimate. RESULTS: The Spearman correlation
      coefficients showed strong positive association among raters, with a range of
      values of 0.66 to 0.90. Internal consistency measured by the Cronbach alpha
      coefficient was excellent (alpha = 0.97). The Kendall coefficient of concordance
      for the ordinal grades suggested a substantial degree of agreement among the
      raters (w = 0.76, p < 0.001). CONCLUSIONS: Static postoperative photographs are a
      reliable outcome measure for determining facial nerve function after vestibular
      schwannoma resection and may serve as a surrogate for the dynamic patient
      interview.

PMID- 22957528
TI  - Incidence of cerebral ischemic events after discontinuation of clopidogrel in
      patients with intracranial aneurysms treated with stent-assisted techniques.
AB  - OBJECT: The optimal antiplatelet medication protocol for prevention of thrombotic
      complications after stent-assisted coil embolization of cerebral aneurysms is
      unclear. Early cessation of antiplatelet agents may be associated with an
      increased risk of cerebral ischemic events. In this study, the authors assess the
      incidence of stroke or transient ischemic attack (TIA) following discontinuation
      of a 6-week course of clopidogrel in patients with cerebral aneurysms treated
      with stent-assisted techniques. METHODS: A retrospective review was conducted in
      all patients with cerebral aneurysms undergoing stent-assisted coil embolization
      or stent-in-stent flow diversion at the University of Iowa during a 24-month
      period. The antiplatelet protocol was 81 mg aspirin and 75 mg clopidogrel daily
      for 6 weeks, followed by 325 mg aspirin daily indefinitely. The incidence of
      stroke or TIA was determined by a retrospective review of medical records
      generated during a 3-month period following discontinuation of clopidogrel.
      RESULTS: A total of 154 patients underwent aneurysm treatment with stent
      techniques during this interval. Documentation of neurological follow-up 3 months
      after discontinuation of a 6-week clopidogrel treatment was available in 121
      (78.6%) of 154 patients. Of these 121 patients, 114 were treated with stent
      assisted coil embolization and 7 with stent-in-stent flow diversion. Six patients
      (5%) suffered an ischemic event after cessation of clopidogrel, with 2 events
      occurring within the first 2 weeks. Specifically, the rate of ischemic events was
      5 (4.3%) of 114 in the "stent-coil" treatment group and 1 (14.3%) of 7 in the
      stent-in-stent group. Treatment had been performed in the setting of a
      subarachnoid hemorrhage in 1 patient. Atypical aneurysm features and technical
      factors predisposing to thrombotic events were found in all but one of these
      patients. Similarly, cardiovascular risk factors were present in 5 of the 6
      patients in whom ischemic events developed after clopidogrel discontinuation.
      CONCLUSIONS: Clopidogrel discontinuation is associated with a 5% risk of ischemic
      events in patients treated with stent techniques. Any stroke related to
      clopidogrel discontinuation is avoidable, and longer treatment is therefore
      clearly necessary. Patients with cardiovascular risk factors, high-risk aneurysm
      features, and those undergoing stent-in-stent flow diversion might benefit the
      most from longer clopidogrel therapy.

PMID- 22957529
TI  - Foix-Chavany-Marie syndrome caused by a disconnection between the right pars
      opercularis of the inferior frontal gyrus and the supplementary motor area.
AB  - Foix-Chavany-Marie syndrome (FCMS) is a rare type of suprabulbar palsy
      characterized by an automatic-voluntary dissociation of the orofacial
      musculature. Here, the authors report an original case of FCMS that occurred
      intraoperatively while resecting the pars opercularis of the inferior frontal
      gyrus. This 25-year-old right-handed man with an incidentally diagnosed right
      frontotemporoinsular tumor underwent surgery using an asleep-awake-asleep
      technique with direct cortical and subcortical electrical stimulation and a
      transopercular approach to the insula. While resecting the anterior part of the
      pars opercularis the patient suffered sudden anarthria and bilateral facial
      weakness. He was unable to speak or show his teeth on command, but he was able to
      voluntarily move his upper and lower limbs. This syndrome lasted for 8 days.
      Postoperative diffusion tensor imaging tractography revealed that connections of
      the pars opercularis of the right inferior frontal gyrus with the frontal aslant
      tract (FAT) and arcuate fasciculus (AF) were damaged. This case supplies evidence
      for localizing the structural substrate of FCMS. It was possible, for the first
      time in the literature, to accurately correlate the occurrence of FCMS to the
      resection of connections between the FAT and AF, and the right pars opercularis
      of the inferior frontal gyrus. The FAT has been recently described, but it may be
      an important connection to mediate supplementary motor area control of orofacial
      movement. The present case also contributes to our knowledge of complication
      avoidance in operculoinsular surgery. A transopercular approach to
      insuloopercular gliomas can generate FCMS, especially in cases of previous
      contralateral lesions. The prognosis is favorable, but the patient should be
      informed of this particular hazard, and the surgeon should anticipate the
      surgical strategy in case the syndrome occurs intraoperatively in an awake
      patient.

PMID- 22957530
TI  - Thrombin-triggered angiogenesis in rat brains following experimental
      intracerebral hemorrhage.
AB  - OBJECT: Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin
      mediates mitogenesis and survival in endothelial cells and induces angiogenesis.
      The present study aimed to clarify whether thrombin is involved in triggering ICH
      related angiogenesis. METHODS: In the first part of the experiment, autologous
      blood (with or without hirudin) was injected to induce ICH. In the second part,
      rats received either 1 U (50 MUl) thrombin or 50 MUl 0.9% sterile saline. In both
      parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains
      were perfused to identify BrdU-positive/von Willebrand factor (vWF)-positive
      nuclei. The expression of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular
      endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated
      by immunohistochemistry and quantitative real-time reverse transcription
      polymerase chain reaction. RESULTS: After ICH, the number of BrdU-/vWF-positive
      nuclei increased until Day 14, and vessels positive for HIF-1alpha, VEGF, Ang-1,
      and Ang-2 were observed around the clot. Quantitative analysis showed that ICH
      upregulated expression of HIF-1alpha, VEGF, Ang-1, and Ang-2 notably compared
      with that in sham controls (p < 0.05). However, hirudin significantly inhibited
      these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei
      and HIF-1alpha-, VEGF-, Ang-1- and Ang-2-positive vessels could be detected
      around the affected region. CONCLUSIONS: Thrombin can induce angiogenesis in rat
      brains and may be an important trigger for ICH-related angiogenesis.

PMID- 22957531
TI  - Differences in simple morphological variables in ruptured and unruptured middle
      cerebral artery aneurysms.
AB  - OBJECT: Management of unruptured intracranial aneurysms remains controversial in
      neurosurgery. The contribution of morphological parameters has not been included
      in the treatment paradigm in a systematic manner or for any particular aneurysm
      location. The authors present a large sample of middle cerebral artery (MCA)
      aneurysms that were assessed using morphological variables to determine the
      parameters associated with aneurysm rupture. METHODS: Preoperative CT angiography
      (CTA) studies were evaluated using Slicer software to generate 3D models of the
      aneurysms and their surrounding vascular architecture. Morphological parameters
      examined in each model included 5 variables already defined in the literature
      (aneurysm size, aspect ratio, aneurysm angle, vessel angle, and size ratio) and 3
      novel variables (flow angle, distance to the genu, and parent-daughter angle).
      Univariate and multivariate statistical analyses were performed to determine
      statistical significance. RESULTS: Between 2005 and 2008, 132 MCA aneurysms were
      treated at a single institution, and CTA studies of 79 aneurysms (40 ruptured and
      39 unruptured) were analyzed. Fifty-three aneurysms were excluded because of
      reoperation (4), associated AVM (2), or lack of preoperative CTA studies (47).
      Ruptured aneurysms were associated with larger size, greater aspect ratio, larger
      aneurysm and flow angles, and smaller parent-daughter angle. Multivariate
      logistic regression revealed that aspect ratio, flow angle, and parent-daughter
      angle were the strongest factors associated with ruptured aneurysms. CONCLUSIONS:
      Aspect ratio, flow angle, and parent-daughter angle are more strongly associated
      with ruptured MCA aneurysms than size. The association of parameters independent
      of aneurysm morphology with ruptured aneurysms suggests that these parameters may
      be associated with an increased risk of aneurysm rupture. These factors are
      readily applied in clinical practice and should be considered in addition to
      aneurysm size when assessing the risk of aneurysm rupture specific to the MCA
      location.

PMID- 22957532
TI  - Diaphragmatic height index: new diagnostic test for phrenic nerve dysfunction.
AB  - OBJECT: The diaphragmatic height index (DHI) was developed to measure the
      difference in diaphragm levels. The purpose of this study was to set definite DHI
      values and test the accuracy of these values for use as a new diagnostic test for
      phrenic nerve dysfunction. METHODS: All data for this study were obtained from
      medical charts and retrospectively reviewed. RESULTS: One hundred sixty-five
      patients with brachial plexus injury who had undergone nerve transfers between
      2005 and 2008 were divided into Groups A and B. Group A consisted of 40 patients
      (mean age 28.0 years) who had sustained concomitant injury of the brachial plexus
      and phrenic nerves. Patients in Group A1 had right phrenic nerve injury and those
      in Group A2 had left phrenic nerve injury. Intraoperative direct electrical
      stimulation of the phrenic nerve was considered the gold standard in assessing
      nerve function in all patients with brachial plexus injury. Group B consisted of
      125 patients (mean age 28.7 years) with brachial plexus injury and normal phrenic
      nerve function. Group C, the control group, consisted of 80 patients with
      nonbrachial plexus injury (mean age 34.0 years) who had undergone other kinds of
      orthopedic operations between April and June 2009. Standard posteroanterior chest
      radiographs were blindly interpreted using the Siriraj inhouse picture archiving
      and communication system in all 245 patients in the study. First, a reference
      line (R line) was drawn along the inferior endplate of T-10. Then, 2 lines (lines
      A and B) were drawn through the highest point of each diaphragm and parallel to
      the R line. The difference between these 2 lines divided by the height of T-10
      was defined as the DHI. The cutoff points of the DHI for diagnosing right and
      left phrenic nerve dysfunction were analyzed with a receiver operating
      characteristic curve. The accuracy of these DHI values was then evaluated. The
      DHI in Group C was 0.64 +/- 0.44, slightly higher than the DHI in Group B, with
      no significant difference. Diaphragmatic height indexes in Groups A1 and A2 were
      2.0 +/- 0.99 and -1.04 +/- 0.83, respectively, which were significantly different
      from those in Groups B and C (p < 0.05). The cutoff point of the DHI for
      diagnosing right phrenic nerve dysfunction was > 1.1, and that for left phrenic
      nerve dysfunction was < 0.2. The sensitivity and specificity of right and left
      DHI values were 90.5% and 86.3%, and 94.7 and 88.3%, respectively. CONCLUSIONS:
      Data in this study show that diaphragm paralysis can be simply and reliably
      predicted by the DHI. Diaphragmatic height index values > 1.1 and < 0.2 are
      proposed as the new diagnostic test for right and left phrenic nerve dysfunction
      with a high degree of accuracy. This index is applicable in diagnosing phrenic
      nerve dysfunction that occurs concomitantly with brachial plexus injury or from
      other etiologies.

PMID- 22957533
TI  - Assessment of integrase interactor 1 (INI-1) expression in primary tumours of
      bone.

PMID- 22957534
TI  - Leukaemic phase as initial presentation of primary bone anaplastic lymphoma
      kinase-negative anaplastic large cell lymphoma.

PMID- 22957535
TI  - Prevalence of anxiety and depressive symptoms in adolescents with asthma: a meta
      analysis and meta-regression.
AB  - It remains unclear whether anxiety and depressive symptoms are more prevalent in
      adolescents with asthma when compared with healthy individuals. This meta
      analysis aimed to evaluate the difference in the aggregate prevalence of
      depressive and anxiety symptoms between adolescents with asthma and healthy
      controls and to explore the underlying moderators that potentially explain the
      heterogeneity of the effect size. A meta-analysis of published work was performed
      using the random effects model. The differences in aggregate prevalence of
      depressive and anxiety symptoms between adolescents with asthma and healthy
      controls were determined. Meta-regression and subgroup analysis were performed to
      identify factors that may contribute to heterogeneity. A total of eight studies
      were eligible for analysis. The aggregate prevalence of depressive and anxiety
      symptoms was significantly higher among 3546 adolescents with asthma than that of
      24,884 controls (depression, 0.27; 95% CI, 0.18.6-0.39 vs. 0.13; 95% CI, 0.09
      0.19; anxiety, 0.33; 95% CI, 0.19-0.52 vs. 0.21; 95% CI, 0.12-0.33). The risk of
      developing depression and anxiety is significantly higher among adolescents with
      asthma when compared with controls (depression: pooled odds ratio, 2.09; 95% CI,
      1.65-2.64; p < 0.001; anxiety: pooled odds ratio, 1.83; 95% CI, 1.63-2.07; p <
      0.001). Meta-regression revealed that the proportions of Caucasian (p = 0.008)
      and smokers (p < 0.001) were significant moderators which explained the
      significant heterogeneity when comparing the risk of developing depressive
      symptoms among adolescent asthma patients vs. controls while age, gender, and
      severity of asthma were not significant. Family doctors, pediatricians, and
      healthcare providers should formulate strategies to detect depressive and anxiety
      symptoms in adolescents with asthma and offer psychological interventions to
      reduce the burden of psychiatric comorbidity.

PMID- 22957536
TI  - Occupational dermatitis in hairdressers: do they claim workers' compensation?
AB  - BACKGROUND: Hairdressers are one of the largest occupational groups attending our
      Occupational Dermatology Clinic. However, few seek workers' compensation for
      their occupational dermatitis. OBJECTIVES: To retrospectively analyse and compare
      workers' compensation claims data and diagnosed disease data for occupational
      contact dermatitis in hairdressers from 1993 to 2009, for the state of Victoria,
      Australia. PATIENTS/MATERIALS/METHODS: Data from the Occupational Dermatology
      Clinic database, the Compensation Research Database and the Australian Bureau of
      Statistics were used in this study. RESULTS: The clinic database identified 157
      hairdressers and apprentices with a confirmed diagnosis of occupational contact
      dermatitis assessed between 1993 and 2009. Forty-six unique claims for
      occupational contact dermatitis from 46 individuals were identified from the
      Compensation Research Database over the same time period. Hairdressers in the 15
      24-year age group were significantly over-represented in the claims data relative
      to the diagnosed disease data (p < 0.01). The median cost per claim was AU$1421,
      and the median time off work per claim was 20 days. CONCLUSION: Increased efforts
      are needed to reduce the incidence of occupational contact dermatitis in
      hairdressers in Australia, and to ensure that hairdressers with occupational
      contact dermatitis are aware of their compensation entitlements. Reliance on
      workers' compensation data for disease surveillance may lead occupational health
      and safety regulators to underestimate the magnitude of the problem of
      occupational contact dermatitis in the hairdressing profession.

PMID- 22957538
TI  - Clustered juvenile xanthogranuloma.
AB  - Clustered or agminated juvenile xanthogranuloma (JXG) is an unusual form of JXG
      characterized by multiple reddish-brown or yellowish papules and nodules in a
      coalescent pattern. We report a case of clustered JXG involving the left lower
      back of a 5-month-old boy. 

PMID- 22957539
TI  - Contact mechanics and three-dimensional alignment of normal dog elbows.
AB  - OBJECTIVE: To evaluate the effects of antebrachial rotation at 3 elbow flexion
      angles on contact mechanics and 3-dimensional (3D) alignment of normal dog
      elbows. STUDY DESIGN: Ex vivo biomechanical study. ANIMALS: Unpaired thoracic
      limbs from 18 dogs (mean +/- SD weight, 27 +/- 4 kg). METHODS: With the limb
      under 200 N axial load, digital pressure sensors measured contact area (CA), mean
      contact pressure (MCP), peak contact pressure (PCP), and PCP location in the
      medial and lateral elbow compartments, and 3D static poses of the elbow were
      obtained. Each specimen was tested at 115 degrees , 135 degrees , and 155 degrees
      elbow flexion, with the antebrachium in a neutral position, in 28 degrees 
      supination, and in 16 degrees  pronation. Repeated measure ANOVAs with post-hoc
      Bonferroni (P <= .0167) were performed. RESULTS: Both pronation and supination
      decreased CA by 16% and 8% and increased PCP by 5% and 10% in the medial and
      lateral compartments, respectively. PCP location moved 2.3 mm (1.8-3.2 mm) closer
      to the apex of the medial coronoid process in pronation and 2.0 mm (1.8-2.2 mm)
      farther away in supination. The radial head and medial coronoid process rotated
      5.4 degrees  and 1.9 degrees  internally during pronation and 7.2 degrees  and
      1.2 degrees  externally during supination. CONCLUSIONS: Contact mechanics and 3D
      alignment of normal dog elbows varied significantly at different elbow poses.

PMID- 22957537
TI  - Importance of cholesterol in dopamine transporter function.
AB  - The conformation and function of the dopamine transporter (DAT) can be affected
      by manipulating membrane cholesterol, yet there is no agreement as to the impact
      of cholesterol on the activity of lipid-raft localized DATs compared with non
      raft DATs. Given the paucity of information regarding the impact of cholesterol
      on substrate efflux by the DAT, this study explores its influence on the kinetics
      of DAT-mediated DA efflux induced by dextroamphetamine, as measured by rotating
      disk electrode voltammetry (RDEV). Treatment with methyl-beta-cyclodextrin
      (mbetaCD), which effectively depletes total membrane cholesterol--uniformly
      affecting cholesterol-DAT interactions in both raft and non-raft membrane domains
      -reduced both DA uptake and efflux rate. In contrast, disruption of raft
      localized DAT by cholesterol chelation with nystatin had no effect, arguing
      against a vital role for raft-localized DAT in substrate uptake or efflux.
      Supranormal repletion of cholesterol-depleted cells with the analog desmosterol,
      a non-raft promoting sterol, was as effective as cholesterol itself in restoring
      transport rates. Further studies with Zn(2+)  and the conformationally biased
      W84L DAT mutant supported the idea that cholesterol is important for maintaining
      the outward-facing DAT with normal rates of conformational interconversions.
      Collectively, these results point to a role for direct cholesterol-DAT
      interactions in regulating DAT function.

PMID- 22957540
TI  - Investigation of HIV-1 assembly and release using modern fluorescence imaging
      techniques.
AB  - The replication of HIV-1, like that of all viruses, is intimately connected with
      cellular structures and pathways. For many years, bulk biochemical and cell
      biological methods were the main approaches employed to investigate interactions
      between HIV-1 and its host cell. However, during the past decade advancements in
      fluorescence imaging technologies opened new possibilities for the direct
      visualization of individual steps occurring throughout the viral replication
      cycle. Electron microscopy (EM) methods, which have traditionally been employed
      for the study of viruses, are complemented by fluorescence microscopy (FM)
      techniques that allow us to follow the dynamics of virus-cell interaction.
      Subdiffraction fluorescence microscopy, as well as correlative EM/FM approaches,
      are narrowing the fundamental gap between the high structural resolution provided
      by EM and the high temporal resolution and throughput accomplished by FM. The
      application of modern microscopy to the study of HIV-1-host cell interactions has
      provided insights into the biology of the virus which could not easily, or not at
      all, have been gained by other methods. Here, we review how modern fluorescence
      imaging techniques enhanced our knowledge of the dynamic and structural changes
      involved in HIV-1 particle formation.

PMID- 22957541
TI  - Communication: Frequency shifts of an intramolecular hydrogen bond as a measure
      of intermolecular hydrogen bond strengths.
AB  - Infrared-ultraviolet double resonance spectroscopy has been applied to study the
      infrared spectra of the supersonically cooled gas phase complexes of formic acid,
      acetic acid, propionic acid, formamide, and water with 9-hydroxy-9
      fluorenecarboxylic acid (9HFCA), an analog of glycolic acid. In these complexes
      each binding partner to 9HFCA can function as both proton donor and acceptor.
      Relative to its frequency in free 9HFCA, the 9-hydroxy (9OH) stretch is blue
      shifted in complexes with formic, acetic, and propionic acids, but is red shifted
      in the complexes with formamide and water. Density functional calculations on
      complexes of 9HFCA to a variety of H bonding partners with differing proton donor
      and acceptor abilities reveal that the quantitative frequency shift of the 9OH
      can be attributed to the balance struck between two competing intermolecular H
      bonds. More extensive calculations on complexes of glycolic acid show excellent
      consistency with the experimental frequency shifts.

PMID- 22957543
TI  - Electron stimulated desorption, DIET, and photochemistry at surfaces: a personal
      recollection.
AB  - A personal recollection of the beginning of the field of photochemistry on
      surfaces is given.

PMID- 22957544
TI  - Electronically induced surface reactions: evolution, concepts, and perspectives.
AB  - This is a personal account of the development of the title subject which is the
      broader field encompassing surface photochemistry. It describes the early times
      when the main interest centered on desorption induced by slow electrons, follows
      its evolution in experiment (use of synchrotron radiation and connections to
      electron spectroscopies; use of lasers) and mechanisms, and briefly mentions the
      many different subfields that have evolved. It discusses some practically
      important aspects and applications and ends with an account of an evolving new
      subfield, the application to photochemistry on nanoparticles.

PMID- 22957545
TI  - The road to hot electron photochemistry at surfaces: a personal recollection.
AB  - A very important part of contemporary fs-laser surface photochemistry (SPC) is
      based on a proposed mechanism in which a laser pulse incident upon an adsorbate
      covered surface photoexcites substrate electrons which in turn inelastically
      scatter from atoms and molecules (chemists may call them "reactants") in or on
      the surface. The present narrative outlines my own very personal SPC saga that
      began with early exposure to the wonders of and fascination with inelastic
      resonant electron scattering from gas phase atoms and molecules that dominated
      the Atomic and Electron Physics activities at NBS (now NIST) in 1968 when I
      arrived. How this lead to a fundamental understanding of important aspects of SPC
      is the focus of this essay.

PMID- 22957546
TI  - Photoexcitation of adsorbates on metal surfaces: one-step or three-step.
AB  - In this essay we discuss the light-matter interactions at molecule-covered metal
      surfaces that initiate surface photochemistry. The hot-electron mechanism for
      surface photochemistry, whereby the absorption of light by a metal surface
      creates an electron-hole pair, and the hot electron scatters through an
      unoccupied resonance of adsorbate to initiate nuclear dynamics leading to
      photochemistry, has become widely accepted. Yet, ultrafast spectroscopic
      measurements of molecule-surface electronic structure and photoexcitation
      dynamics provide scant support for the hot electron mechanism. Instead, in most
      cases the adsorbate resonances are excited through photoinduced substrate-to
      adsorbate charge transfer. Based on recent studies of the role of coherence in
      adsorbate photoexcitation, as measured by the optical phase and momentum resolved
      two-photon photoemission measurements, we examine critically the hot electron
      mechanism, and propose an alternative description based on direct charge transfer
      of electrons from the substrate to adsorbate. The advantage of this more quantum
      mechanically rigorous description is that it informs how material properties of
      the substrate and adsorbate, as well as their interaction, influence the
      frequency dependent probability of photoexcitation and ultimately how light can
      be used to probe and control surface femtochemistry.

PMID- 22957547
TI  - Toward photochemistry of integrated heterogeneous systems.
AB  - This paper begins with describing the excitation mechanisms in surface
      photochemistry and nuclear dynamics of adsorbate induced by electronic
      excitation. An illustrative example is Cs adsorbate on a Cu(111) surface. This
      adsorption system shows drastic changes in the electronic structure with
      coverage; this allows us to examine different types of electronic excitations
      that stimulate nuclear motions of Cs. Remarks are made on challenges in
      photoinduced processes at well-defined surfaces: direct observations of adsorbate
      substrate vibrational modes and photoinduced reactions between adsorbates. Then,
      the paper addresses some issues in more complex systems: metal-liquid interfaces
      and powdered photocatalysts of metal oxides. Photochemistry and photoinduced
      nuclear dynamics at metal-liquid interfaces have not been well explored. Studies
      on this subject may make it possible to bridge the gap between surface
      photochemistry and electrochemistry. Photocatalysis with powdered catalysts has
      been extensively studied and is still an active area, but our understanding of
      the mechanism of photocatalysis is far from satisfactory. Although complicated,
      the highly integrated systems provide an opportunity to extend our knowledge of
      surface photochemistry.

PMID- 22957548
TI  - Surface aligned reaction.
AB  - This paper reflects on three decades during which the study of surface aligned
      reaction (SAR) has advanced. The objective in SAR, which in considerable part
      still lies ahead, is the simultaneous control of atomic and molecular "collision
      energies, collision angles, and impact parameter." Following a discussion of the
      benefits of such an approach we review the progress made, and, as a stimulus to
      experiment, present new calculations of SAR dynamics for bimolecular reaction at
      a metal surface. It seems reasonable to suppose that we are now entering a decade
      in which a combination of scanning tunneling microscopy and femtosecond laser
      spectroscopy will bring the full realisation of SAR.

PMID- 22957549
TI  - Application of discrete variable representation to planar H2+ in strong xuv laser
      fields.
AB  - We present an efficient and accurate grid method to study the strong field
      dynamics of planar H(2)(+) under Born-Oppenheimer approximation. After
      introducing the elliptical coordinates to the planar H(2)(+), we show that the
      Coulomb singularities at the nuclei can be successfully overcome so that both
      bound and continuum states can be accurately calculated by the method of
      separation of variables. The time-dependent Schrodinger equation (TDSE) can be
      accurately solved by a two-dimensional discrete variable representation (DVR)
      method, where the radial coordinate is discretized with the finite-element
      discrete variable representation for easy parallel computation and the angular
      coordinate with the trigonometric DVR which can describe the periodicity in this
      direction. The bound states energies can be accurately calculated by the
      imaginary time propagation of TDSE, which agree very well with those computed by
      the separation of variables. We apply the TDSE to study the ionization dynamics
      of the planar H(2)(+) by short extreme ultra-violet (xuv) pulses, in which case
      the differential momentum distributions from both the length and the velocity
      gauge agree very well with those calculated by the lowest order perturbation
      theory.

PMID- 22957550
TI  - One-electron contributions to the g-tensor for second-order Douglas-Kroll-Hess
      theory.
AB  - The electric g-tensor is a central quantity for the interpretation of electron
      paramagnetic resonance spectra. In this paper, a detailed derivation of the 1
      electron contributions to the g-tensor is presented in the framework of linear
      response theory and the second-order Douglas-Kroll-Hess (DKH) transformation.
      Importantly, the DKH transformation in the presence of a magnetic field is not
      unique. Whether or not the magnetic field is included in the required Foldy
      Wouthuysen transformation, different transformation matrices and, consequently,
      Hamiltonians result. In this paper, a detailed comparison of both approaches is
      presented, paying particular attention to the mathematical properties of the
      resulting Hamiltonians. In contrast to previous studies that address the g-tensor
      in the framework of DKH theory, the resulting terms are compared to those of the
      conventional Pauli theory and are given a physical interpretation. Based on these
      mathematical and physical arguments, we establish that the proper DKH
      transformation for systems with constant magnetic fields is based on a gauge
      invariant Foldy-Wouthuysen transformation, i.e., a Foldy-Wouthuysen
      transformation including the magnetic field. Calculations using density
      functional theory (DFT) are carried out on a set of heavy, diatomic molecules,
      and a set of transition-metal complexes. Based on these calculations, the
      performance of the relativistic calculation with and without inclusion of picture
      change effects is compared. Additionally, the g-tensor is calculated for the
      Lanthanide dihydrides. Together with the results from the other two molecular
      test sets, these calculations serve to quantify the magnitude of picture-change
      effects and elucidate trends across the periodic table.

PMID- 22957551
TI  - Homonuclear decoupling for liquid-state NMR.
AB  - We present a solution to the problem of decoupling of a homonuclear two-spin
      system having weak isotropic scalar coupling. We describe non-selective pulse
      sequences that create an effective field perpendicular to the coupling
      interaction over a broad range of chemical shifts, with a magnitude proportional
      to the chemical shifts. Effective decoupling is achieved when the difference in
      chemical shifts imprinted on the perpendicular field is sufficiently larger than
      the coupling between the spins. The proposed methods scale down the chemical
      shifts. The pulse sequences may be useful in various applications in nuclear
      magnetic resonance spectroscopy.

PMID- 22957552
TI  - Development and applications of a unitary group adapted state specific multi
      reference coupled cluster theory with internally contracted treatment of inactive
      double excitations.
AB  - Any multi-reference coupled cluster (MRCC) development based on the Jeziorski
      Monkhorst (JM) multi-exponential ansatz for the wave-operator Omega suffers from
      spin-contamination problem for non-singlet states. We have very recently proposed
      a spin-free unitary group adapted (UGA) analogue of the JM ansatz, where the
      cluster operators are defined in terms of spin-free unitary generators and a
      normal ordered, rather than ordinary, exponential parametrization of Omega is
      used. A consequence of the latter choice is the emergence of the "direct term" of
      the MRCC equations that terminates at exactly the quartic power of the cluster
      amplitudes. Our UGA-MRCC ansatz has been utilized to generate both the spin-free
      state specific (SS) and the state universal MRCC formalisms. It is well-known
      that the SSMRCC theory requires suitable sufficiency conditions to resolve the
      redundancy of the cluster amplitudes. In this paper, we propose an alternative
      variant of the UGA-SSMRCC theory, where the sufficiency conditions are used for
      all cluster operators containing active orbitals and the single excitations with
      inactive orbitals, while the inactive double excitations are assumed to be
      independent of the model functions they act upon. The working equations for the
      inactive double excitations are thus derived in an internally contracted (IC)
      manner in the sense that the matrix elements entering the MRCC equations involve
      excitations from an entire combination of the model functions. We call this
      theory as UGA-ICID-MRCC, where ICID is the acronym for "Internally Contracted
      treatment of Inactive Double excitations." Since the number of such excitations
      are the most numerous, choosing them to be independent of the model functions
      will lead to very significant reduction in the number of cluster amplitudes for
      large active spaces, and is worth exploring. Moreover, unlike for the excitations
      involving active orbitals, where there is inadequate coupling between the model
      and the virtual functions in the SSMRCC equations generated from sufficiency
      conditions, our internally contracted treatment of inactive double excitations
      involves much more complete couplings. Numerical implementation of our formalism
      amply demonstrates the efficacy of the formalism.

PMID- 22957553
TI  - Extended diffusion in a double well potential: transition from classical to
      quantum regime.
AB  - The transition between the classical and quantum regimes in the diffusion of a
      particle in a 2-4 double-well potential is treated via the strong collision model
      in the high-temperature limit. Both the classical and semiclassical position
      correlation functions, their spectra, and correlation times are evaluated using
      the memory function formalism. It is shown that even in the high temperature
      limit, marked classical-quantum transition effects appear in the observables when
      collisions are rare.

PMID- 22957554
TI  - Transition path sampling for discrete master equations with absorbing states.
AB  - Transition path sampling (TPS) algorithms have been implemented with
      deterministic dynamics, with thermostatted dynamics, with Brownian dynamics, and
      with simple spin flip dynamics. Missing from the TPS repertoire is an
      implementation with kinetic Monte Carlo (kMC), i.e., with the underlying dynamics
      coming from a discrete master equation. We present a new hybrid kMC-TPS algorithm
      and prove that it satisfies detailed balance in the transition path ensemble. The
      new algorithm is illustrated for a simplified Markov State Model of trp-cage
      folding. The transition path ensemble from kMC-TPS is consistent with that
      obtained from brute force kMC simulations. The committor probabilities and local
      fluxes for the simple model are consistent with those obtained from exact methods
      for simple master equations. The new kMC-TPS method should be useful for analysis
      of rare transitions in complex master equations where the individual states
      cannot be enumerated and therefore where exact solutions cannot be obtained.

PMID- 22957555
TI  - Enhancement of coherent energy transport by disorder and temperature in light
      harvesting processes.
AB  - We investigate the influence of static disorder and thermal excitations on
      excitonic energy transport in the light-harvesting apparatus of photosynthetic
      systems by solving the Schrodinger equation and taking into account the coherent
      hoppings of excitons, the rates of exciton creation and annihilation in antennas
      and reaction centers, and the coupling to thermally excited phonons. The antennas
      and reaction centers are modeled, respectively, as the sources and drains which
      provide the channels for creation and annihilation of excitons. Phonon modes
      below a maximum frequency are coupled to the excitons that are continuously
      created in the antennas and depleted in the reaction centers, and the phonon
      population in these modes obeys the Bose-Einstein distribution at a given
      temperature. It is found that the energy transport is not only robust against the
      static disorder and the thermal noise, but it can also be enhanced by increasing
      the randomness and temperature in most parameter regimes. Relevance of our work
      to the highly efficient energy transport in photosynthetic systems is discussed.

PMID- 22957556
TI  - A general theory of DNA-mediated and other valence-limited colloidal
      interactions.
AB  - We present a general theory for predicting the interaction potentials between DNA
      coated colloids, and more broadly, any particles that interact via valence
      limited ligand-receptor binding. Our theory correctly incorporates the
      configurational and combinatorial entropic factors that play a key role in
      valence-limited interactions. By rigorously enforcing self-consistency, it
      achieves near-quantitative accuracy with respect to detailed Monte Carlo
      calculations. With suitable approximations and in particular geometries, our
      theory reduces to previous successful treatments, which are now united in a
      common and extensible framework. We expect our tools to be useful to other
      researchers investigating ligand-mediated interactions. A complete and well
      documented Python implementation is freely available at
      http://github.com/patvarilly/DNACC.

PMID- 22957557
TI  - Exploiting time-independent Hamiltonian structure as controls for manipulating
      quantum dynamics.
AB  - The opportunities offered by utilizing time-independent Hamiltonian structure as
      controls are explored for manipulating quantum dynamics. Two scenarios are
      investigated using different manifestations of Hamiltonian structure to
      illustrate the generality of the concept. In scenario I, optimally shaped
      electrostatic potentials are generated to flexibly control electron scattering in
      a two-dimensional subsurface plane of a semiconductor. A simulation is performed
      showing the utility of optimally setting the individual voltages applied to a
      multi-pixel surface gate array in order to produce a spatially inhomogeneous
      potential within the subsurface scattering plane. The coherent constructive and
      destructive electron wave interferences are manipulated by optimally adjusting
      the potential shapes to alter the scattering patterns. In scenario II, molecular
      vibrational wave packets are controlled by means of optimally selecting the
      Hamiltonian structure in cooperation with an applied field. As an illustration of
      the concept, a collection (i.e., a level set) of dipole functions is identified
      where each member serves with the same applied electric field to produce the
      desired final transition probability. The level set algorithm additionally found
      Hamiltonian structure controls exhibiting desirable physical properties. The
      prospects of utilizing the applied field and Hamiltonian structure simultaneously
      as controls is also explored. The control scenarios I and II indicate the gains
      offered by algorithmically guided molecular or material discovery for
      manipulating quantum dynamics phenomenon.

PMID- 22957558
TI  - Exact non-additive kinetic potentials in realistic chemical systems.
AB  - In methods based on frozen-density embedding theory or subsystem formulation of
      density functional theory, the non-additive kinetic potential (v(t)(nad)(r))
      needs to be approximated. Since v(t)(nad)(r) is defined as a bifunctional, the
      common strategies rely on approximating v(t)(nad)[rho(A),rho(B)](r). In this
      work, the exact potentials (not bifunctionals) are constructed for chemically
      relevant pairs of electron densities (rho(A) and rho(B)) representing:
      dissociating molecules, two parts of a molecule linked by a covalent bond, or
      valence and core electrons. The method used is applicable only for particular
      case, where rho(A) is a one-electron or spin-compensated two-electron density,
      for which the analytic relation between the density and potential exists. The sum
      rho(A) + rho(B) is, however, not limited to such restrictions. Kohn-Sham
      molecular densities are used for this purpose. The constructed potentials are
      analyzed to identify the properties which must be taken into account when
      constructing approximations to the corresponding bifunctional. It is
      comprehensively shown that the full von Weizsacker component is indispensable in
      order to approximate adequately the non-additive kinetic potential for such pairs
      of densities.

PMID- 22957559
TI  - Real-space, real-time calculation of dynamic hyperpolarizabilities.
AB  - The finite-difference method to calculate hyperpolarizabilities is generalized
      for dynamical case. The calculation of the dynamical hyperpolarizabilities from
      non-perturbative, explicitly time-dependent single particle states obtained in
      the framework of the time-dependent density functional theory, is implemented in
      real space and real time. The optical response functions up to the third order
      are extracted in frequency domain. The present approach is free of deficiencies
      associated with atom centered basis sets and allows treatment of large molecules.
      The calculated results are in good agreement with experiments and with other
      theoretical calculations for various test cases.

PMID- 22957560
TI  - Implementation of the multireference Brillouin-Wigner and Mukherjee's coupled
      cluster methods with non-iterative triple excitations utilizing reference-level
      parallelism.
AB  - In this paper we discuss the performance of the non-iterative state-specific
      multireference coupled cluster (SS-MRCC) methods accounting for the effect of
      triply excited cluster amplitudes. The corrections to the Brillouin-Wigner and
      Mukherjee's MRCC models based on the manifold of singly and doubly excited
      cluster amplitudes (BW-MRCCSD and Mk-MRCCSD, respectively) are tested and
      compared with exact full configuration interaction results for small systems
      (H(2)O, N(2), and Be(3)). For the larger systems (naphthyne isomers) the BW-MRCC
      and Mk-MRCC methods with iterative singles, doubles, and non-iterative triples
      (BW-MRCCSD(T) and Mk-MRCCSD(T)) are compared against the results obtained with
      single reference coupled cluster methods. We also report on the parallel
      performance of the non-iterative implementations based on the use of processor
      groups.

PMID- 22957561
TI  - Magnetizability tensors from auxiliary density functional theory.
AB  - The working equations for the calculation of the magnetizability tensor in the
      framework of auxiliary density functional theory with gauge including atomic
      orbitals (ADFT-GIAO) are derived. Unlike in the corresponding conventional
      density functional theory implementations the numerical integration of the GIAOs
      is avoided in ADFT-GIAO. Our validation shows that this simplification has no
      effect on the accuracy of the methodology. As a result, a reliable and efficient
      implementation for the calculation of magnetizabilities of systems with more than
      1000 atoms and 14,000 basis functions is presented.

PMID- 22957562
TI  - Direct first-principles chemical potential calculations of liquids.
AB  - We propose a scheme that drastically improves the efficiency of Widom's particle
      insertion method by efficiently sampling cavities while calculating the integrals
      providing the chemical potentials of a physical system. This idea enables us to
      calculate chemical potentials of liquids directly from first-principles without
      the help of any reference system, which is necessary in the commonly used
      thermodynamic integration method. As an example, we apply our scheme, combined
      with the density functional formalism, to the calculation of the chemical
      potential of liquid copper. The calculated chemical potential is further used to
      locate the melting temperature. The calculated results closely agree with
      experiments.

PMID- 22957563
TI  - Single-conformation infrared spectra of model peptides in the amide I and amide
      II regions: experiment-based determination of local mode frequencies and inter
      mode coupling.
AB  - Single-conformation infrared spectra in the amide I and amide II regions have
      been recorded for a total of 34 conformations of three alpha-peptides, three beta
      peptides, four alpha/beta-peptides, and one gamma-peptide using resonant ion-dip
      infrared spectroscopy of the jet-cooled, isolated molecules. Assignments based on
      the amide NH stretch region were in hand, with the amide I/II data providing
      additional evidence in favor of the assignments. A set of 21 conformations that
      represent the full range of H-bonded structures were chosen to characterize the
      conformational dependence of the vibrational frequencies and infrared intensities
      of the local amide I and amide II modes and their amide I/I and amide II/II
      coupling constants. Scaled, harmonic calculations at the DFT M05-2X/6-31+G(d)
      level of theory accurately reproduce the experimental frequencies and infrared
      intensities in both the amide I and amide II regions. In the amide I region,
      Hessian reconstruction was used to extract local mode frequencies and amide I/I
      coupling constants for each conformation. These local amide I frequencies are in
      excellent agreement with those predicted by DFT calculations on the corresponding
      (13)C = (18)O isotopologues. In the amide II region, potential energy
      distribution analysis was combined with the Hessian reconstruction scheme to
      extract local amide II frequencies and amide II/II coupling constants. The
      agreement between these local amide II frequencies and those obtained from DFT
      calculations on the N-D isotopologues is slightly worse than for the
      corresponding comparison in the amide I region. The local mode frequencies in
      both regions are dictated by a combination of the direct H-bonding environment
      and indirect, "backside" H-bonds to the same amide group. More importantly, the
      sign and magnitude of the inter-amide coupling constants in both the amide I and
      amide II regions is shown to be characteristic of the size of the H-bonded ring
      linking the two amide groups. These amide I/I and amide II/II coupling constants
      remain similar in size for alpha-, beta-, and gamma-peptides despite the
      increasing number of C-C bonds separating the amide groups. These findings
      provide a simple, unifying picture for future attempts to base the calculation of
      both nearest-neighbor and next-nearest-neighbor coupling constants on a joint
      footing.

PMID- 22957564
TI  - Overlapping resonances interference-induced transparency: the S0 -> S2/S1
      photoexcitation spectrum of pyrazine.
AB  - The phenomenon of "overlapping resonances interference-induced transparency"
      (ORIT) is introduced and studied in detail for the S(0) -> S(2)/S(1)
      photoexcitation of cold pyrazine (C(4)H(4)N(2)). In ORIT, a molecule becomes
      transparent at specific wavelengths due to interferences between envelopes of
      spectral lines displaying overlapping resonances. An example is the S(2) <-> S(1)
      internal conversion in pyrazine where destructive interference between
      overlapping resonances causes the S(0) -> S(2)/S(1) light absorption to disappear
      at certain wavelengths. ORIT may be of practical importance in multi-component
      mixtures where it would allow for the selective excitation of some molecules in
      preference to others. Interference-induced cross section enhancement is also
      shown.

PMID- 22957565
TI  - Dynamically biased statistical model for the ortho/para conversion in the H2 +
      H3+ -> H3+ + H2 reaction.
AB  - In this work we present a dynamically biased statistical model to describe the
      evolution of the title reaction from statistical to a more direct mechanism,
      using quasi-classical trajectories (QCT). The method is based on the one
      previously proposed by Park and Light [J. Chem. Phys. 126, 044305 (2007)]. A
      recent global potential energy surface is used here to calculate the capture
      probabilities, instead of the long-range ion-induced dipole interactions. The
      dynamical constraints are introduced by considering a scrambling matrix which
      depends on energy and determine the probability of the identity/hop/exchange
      mechanisms. These probabilities are calculated using QCT. It is found that the
      high zero-point energy of the fragments is transferred to the rest of the degrees
      of freedom, what shortens the lifetime of H(5)(+) complexes and, as a
      consequence, the exchange mechanism is produced with lower proportion. The zero
      point energy (ZPE) is not properly described in quasi-classical trajectory
      calculations and an approximation is done in which the initial ZPE of the
      reactants is reduced in QCT calculations to obtain a new ZPE-biased scrambling
      matrix. This reduction of the ZPE is explained by the need of correcting the pure
      classical level number of the H(5)(+) complex, as done in classical simulations
      of unimolecular processes and to get equivalent quantum and classical rate
      constants using Rice-Ramsperger-Kassel-Marcus theory. This matrix allows to
      obtain a ratio of hop/exchange mechanisms, alpha(T), in rather good agreement
      with recent experimental results by Crabtree et al. [J. Chem. Phys. 134, 194311
      (2011)] at room temperature. At lower temperatures, however, the present
      simulations predict too high ratios because the biased scrambling matrix is not
      statistical enough. This demonstrates the importance of applying quantum methods
      to simulate this reaction at the low temperatures of astrophysical interest.

PMID- 22957566
TI  - An ab initio based full-dimensional global potential energy surface for
      FH2O(X2A') and dynamics for the F + H2O -> HF + HO reaction.
AB  - A global potential energy surface (PES) for the ground electronic state of FH(2)O
      is constructed based on more than 30,000 ab initio points at the multi-reference
      configuration interaction level. The PES features a pre-reaction van der Waals
      well and two post-reaction hydrogen-bonded complexes, as well as a "reactant
      like" transition state with a classical barrier of 3.8 kcal/mol. The adiabatic F
      + H(2)O -> HF + OH reaction dynamics on this PES was investigated using a
      standard quasi-classical trajectory method. In agreement with experiment, the HF
      product contains significant vibrational excitation with limited rotational
      excitation, while the OH product is internally cold, reflecting its spectator
      role in the reaction. The products are primarily scattered in the backward
      direction, consistent with a direct abstraction mechanism.

PMID- 22957567
TI  - Photodissociation of pyrrole-ammonia clusters below 218 nm: quenching of
      statistical decomposition pathways under clustering conditions.
AB  - The excited state hydrogen transfer (ESHT) reaction in pyrrole-ammonia clusters
      (PyH.(NH(3))(n), n = 2-5) at excitation wavelengths below 218 nm down to 199 nm,
      has been studied using a combination of velocity map imaging and non-resonant
      detection of the NH(4)(NH(3))(n-1) products. Special care has been taken to avoid
      evaporation of solvent molecules from the excited clusters by controlling the
      intensity of both the excitation and probing lasers. The high resolution
      translational energy distributions obtained are analyzed on the base of an
      impulsive mechanism for the hydrogen transfer, which mimics the direct N-H bond
      dissociation of the bare pyrrole. In spite of the low dissociation wavelengths
      attained (~200 nm) no evidence of hydrogen-loss statistical dynamics has been
      observed. The effects of clustering of pyrrole with ammonia molecules on the
      possible statistical decomposition channels of the bare pyrrole are discussed.

PMID- 22957568
TI  - Exact quantum scattering calculation of transport properties for free radicals:
      OH(X2Pi)-helium.
AB  - Transport properties for OH-He are computed through quantum scattering
      calculations using the ab initio potential energy surfaces determined by Lee et
      al. [J. Chem. Phys. 113, 5736 (2000)]. To gauge the importance of the open-shell
      character of OH and the anisotropy of the potential on the transport properties,
      including the collision integrals Omega((1,1)) and Omega((2,2)), as well as the
      diffusion coefficient, calculations were performed with the full potential, with
      the difference potential V(dif) set to zero, and with only the spherical average
      of the potential. Slight differences (3%-5%) in the computed diffusion
      coefficient were found between the values obtained using the full potential and
      the truncated potentials. The computed diffusion coefficients were compared to
      recent experimental measurements and those computed with a Lennard-Jones (LJ) 12
      6 potential. The values obtained with the full potential were slightly higher
      than the experimental values. The LJ 12-6 potential was found to underestimate
      the variation in temperature as compared to that obtained using the full OH-He ab
      initio potential.

PMID- 22957569
TI  - Electric dipole (hyper)polarizabilities of spatially confined LiH molecule.
AB  - In this study we report on the electronic contributions to the linear and
      nonlinear static electronic electric dipole properties, namely the dipole moment
      (MU), the polarizability (alpha), and the first-hyperpolarizability (beta), of
      spatially confined LiH molecule in its ground X (1)Sigma(+) state. The finite
      field technique is applied to estimate the corresponding energy and dipole moment
      derivatives with respect to external electric field. Various forms of confining
      potential, of either spherical or cylindrical symmetry, are included in the
      Hamiltonian in the form of one-electron operator. The computations are performed
      at several levels of approximation including the coupled-cluster methods as well
      as multi-configurational (full configuration interaction) and explicitly
      correlated Gaussian wavefunctions. The performance of Kohn-Sham density
      functional theory for the selected exchange-correlation functionals is also
      discussed. In general, the orbital compression effects lead to a substantial
      reduction in all the studied properties regardless of the symmetry of confining
      potential, however, the rate of this reduction varies depending on the type of
      applied potential. Only in the case of dipole moment under a cylindrical
      confinement a gradual increase of its magnitude is observed.

PMID- 22957570
TI  - Rotationally resolved PFI-ZEKE photoelectron spectroscopic study of the low-lying
      electronic states of ArXe+.
AB  - Rotationally resolved pulsed-field-ionization zero-kinetic-energy photoelectron
      spectra of the X 1/2, A(1) 3/2, and A(2) 1/2 electronic states of the ArXe(+)
      molecular ion have been recorded following resonant (1+1') two-photon excitation
      via selected rovibrational levels of the C 1 and D 0(+) states of selected
      isotopomers of the ArXe molecule. Using rovibronic selection and propensity rules
      for the photoionization out of these intermediate molecular states enabled the
      determination of the parity of the molecular-ion levels and of the magnitude and
      sign of the Omega-doubling constants of the coupled X 1/2 (p ~ 4B) and A(2) 1/2
      (p ~ -2B) states of ArXe(+). The results indicate that these molecular-ion states
      can be approximately described using Mulliken's second variant of Hund's angular
      momentum coupling case (c), for which J(a), the total electronic and spin angular
      momentum of the two atoms, is a good quantum number (semi-united atom). The
      analysis of the rotational structure enabled the derivation of improved values of
      the dissociation energies, equilibrium distances, and molecular constants for the
      X 1/2, A(1) 3/2, and A(2) 1/2 states of ArXe(+).

PMID- 22957571
TI  - Effect of acceptor heteroatoms on pi-hydrogen bonding interactions: a study of
      indole...thiophene heterodimer in a supersonic jet.
AB  - Resonant two photon ionization (R2PI), IR-UV, and UV-UV double resonance
      spectroscopic techniques combined with quantum chemistry calculations have been
      used to determine the structure of indole...thiophene dimer observed in a
      supersonic jet. With the help of combined experimental and theoretical IR spectra
      it has been found that the observed dimer has a N-H...pi hydrogen bonded slanted
      T-shaped structure. The present study demonstrates the effect of heteroatoms
      present in the acceptors on the strength of the pi-hydrogen bonding interactions.
      It was concluded by Sherrill and co-workers from their theoretical study of
      benzene...pyridine dimer that aromatic rings containing heteroatoms are poorest
      pi-hydrogen bond acceptors [E. G. Hohenstein and C. D. Sherrill, J. Phys. Chem. A
      113, 878 (2009)]. But the current spectroscopic investigation exhibits that five
      membered aromatic heterocycles are favorable pi-hydrogen bond acceptors. In this
      study, it has also been shown that thiophene is a better pi-hydrogen bond
      acceptor than furan. The present work has immense biological significance as
      indole is the chromophore of tryptophan residue in the proteins and thiophene
      derivatives have potential therapeutic applications. Thus, understanding the
      binding motif between indole and thiophene in the heterodimer studied in this
      work may help in designing efficient drugs.

PMID- 22957572
TI  - Formation of negative hydrogen ion: polarization electron capture and nonthermal
      shielding.
AB  - The influence of the nonthermal shielding on the formation of the negative
      hydrogen ion (H(-)) by the polarization electron capture are investigated in
      partially ionized generalized Lorentzian plasmas. The Bohr-Lindhard method has
      been applied to obtain the negative hydrogen formation radius and cross section
      as functions of the collision energy, de Broglie wave length, Debye length,
      impact parameter, and spectral index of the plasma. The result shows that the
      nonthermal character of the plasma enhances the formation radius of the negative
      hydrogen, especially, for small Debye radii. It is found that the nonthermal
      effect increases the formation cross section of the negative hydrogen. It is also
      found that the maximum position of the formation cross section approaches to the
      collision center with an increase of the spectral index. In addition, it is found
      that the formation cross section significantly decreases with an increase of the
      Debye length, especially, for small spectral indices.

PMID- 22957573
TI  - Thomson-resonant interference effects in elastic x-ray scattering near the Cl K
      edge of HCl.
AB  - We experimentally observed interference effects in elastic x-ray scattering from
      gas-phase HCl in the vicinity of the Cl K edge. Comparison to theory identifies
      these effects as interference effects between non-resonant elastic Thomson
      scattering and resonant Raman scattering. The results indicate the non-resonant
      Thomson and resonant Raman contributions are of comparable strength. The
      measurements also exhibit strong polarization dependence, allowing an easy
      identification of the resonant and non-resonant contributions.

PMID- 22957574
TI  - Reactive quenching of OH A 2Sigma+ by O2 and CO: experimental and nonadiabatic
      theoretical studies of H- and O-atom product channels.
AB  - The outcomes following collisional quenching of electronically excited OH A
      (2)Sigma(+) by O(2) and CO are examined in a combined experimental and
      theoretical study. The atomic products from reactive quenching are probed using
      two-photon laser-induced fluorescence to obtain H-atom Doppler profiles, O
      ((3)P(J)) atom fine structure distributions, and the relative yields of these
      products with H(2), O(2), and CO collision partners. The corresponding H-atom
      translational energy distributions are extracted for the H + O(3) and H + CO(2)
      product channels, in the latter case revealing that most of the available energy
      is funneled into internal excitation of CO(2). The experimental product branching
      ratios show that the O-atom producing pathways are the dominant outcomes of
      quenching: the OH A (2)Sigma(+) + O(2) -> O + HO(2) channel accounts for 48(3)%
      of products and the OH A (2)Sigma(+) + CO -> O + HCO channel yields 76(5)% of
      products. In addition, quenching of OH A (2)Sigma(+) by O(2) generates H + O(3)
      products [12(3)%] and returns OH to its ground X (2)Pi electronic state [40(1)%;
      L. P. Dempsey, T. D. Sechler, C. Murray, and M. I. Lester, J. Phys. Chem. A 113,
      6851 (2009)]. Quenching of OH A (2)Sigma(+) by CO also yields H + CO(2) reaction
      products [26(5)%]; however, OH X (2)Pi (v" = 0,1) products from nonreactive
      quenching are not observed. Theoretical studies characterize the properties of
      energy minimized conical intersections in four regions of strong nonadiabatic
      coupling accessible from the OH A (2)Sigma(+) + CO asymptote. Three of these
      regions have the O-side of OH pointing toward CO, which lead to atomic H and
      vibrationally excited CO(2) products and/or nonreactive quenching. In the fourth
      region, energy minimized points are located on a seam of conical intersection
      from the OH A (2)Sigma(+) + CO asymptote to an energy minimized crossing with an
      extended OH bond length and the H-side of OH pointing toward CO in a bent
      configuration. This region, exoergic with respect to the reaction asymptote, is
      likely to be the origin of the dominant O + HCO product channel.

PMID- 22957575
TI  - Computational studies of ionic liquids: size does matter and time too.
AB  - Taking the molecular ionic liquid 1-ethyl-3-methylimidazolium triflate as a
      reference system, the size and time dependence of molecular dynamics simulation
      studies is analyzed in a systematic way. Based on an all atom force field,
      trajectories of 70 ns length, covering samples of 8-2000 ion pairs, were
      generated and analyzed in terms of structure as well as single particle and
      collective dynamics. Although 50 ion pairs seemed sufficient for structure, at
      least 500 ion pairs were needed for the correct handling of dynamics. For larger
      systems a linear regime is found, i.e., the respective dynamical properties are a
      linear function of the inverse box length. In case of translational diffusion
      coefficients, this linear relation can be rationalised in hydrodynamic terms. The
      respective formula is essentially determined by viscosity and the inverse box
      length. Concerning the time dependence, consistent dynamical properties required
      a time period of 20-30 ns. Nevertheless, size dependence dominates time
      dependence and has to be primarily addressed.

PMID- 22957576
TI  - The effect of aqueous solutions of trimethylamine-N-oxide on pressure induced
      modifications of hydrophobic interactions.
AB  - To understand the mechanism of protein protection by the osmolyte trimethylamine
      N-oxide (TMAO) at high pressure, using molecular dynamics (MD) simulations,
      solvation of hydrophobic group is probed in aqueous solutions of TMAO over a wide
      range of pressures relevant to protein denaturation. The hydrophobic solute
      considered in this study is neopentane which is a considerably large molecule.
      The concentrations of TMAO range from 0 to 4 M and for each TMAO concentration,
      simulations are performed at five different pressures ranging from 1 atm to 8000
      atm. Potentials of mean force are calculated and the relative stability of
      solvent-separated state over the associated state of hydrophobic solute are
      estimated. Results suggest that high pressure reduces association of hydrophobic
      solutes. From computations of site-site radial distribution function followed by
      analysis of coordination number, it is found that water molecules are tightly
      packed around the nonpolar particle at high pressure and the hydration number
      increases with increasing pressure. On the other hand, neopentane interacts
      preferentially with TMAO over water and although hydration of neopentane reduces
      in presence of this osmolyte, TMAO does not show any tendency to prevent the
      pressure-induced dispersion of neopentane moieties. It is also observed that TMAO
      molecules prefer a side-on orientation near the neopentane surface, allowing its
      oxygen atom to form favorable hydrogen bonds with water while maintaining some
      hydrophobic contacts with neopentane. Analysis of hydrogen-bond properties and
      solvation characteristics of TMAO reveals that TMAO can form hydrogen bonds with
      water and it reduces the identical nearest neighbor water molecules caused by
      high hydrostatic pressures. Moreover, TMAO enhances life-time of water-water
      hydrogen bonds and makes these hydrogen bonds more attractive. Implication of
      these results for counteracting effect of TMAO against protein denaturation at
      high pressures are discussed.

PMID- 22957577
TI  - High resolution NMR study of T1 magnetic relaxation dispersion. III. Influence of
      spin 1/2 hetero-nuclei on spin relaxation and polarization transfer among
      strongly coupled protons.
AB  - Effects of spin-spin interactions on the nuclear magnetic relaxation dispersion
      (NMRD) of protons were studied in a situation where spin 1/2 hetero-nuclei are
      present in the molecule. As in earlier works [K. L. Ivanov, A. V. Yurkovskaya,
      and H.-M. Vieth, J. Chem. Phys. 129, 234513 (2008); S. E. Korchak, K. L. Ivanov,
      A. V. Yurkovskaya, and H.-M. Vieth, ibid. 133, 194502 (2010)], spin-spin
      interactions have a pronounced effect on the relaxivity tending to equalize the
      longitudinal relaxation times once the spins become strongly coupled at a
      sufficiently low magnetic field. In addition, we have found influence of (19)F
      nuclei on the proton NMRD, although in the whole field range, studied protons and
      fluorine spins were only weakly coupled. In particular, pronounced features in
      the proton NMRD were found; but each feature was predominantly observed only for
      particular spin states of the hetero-nuclei. The features are explained
      theoretically; it is shown that hetero-nuclei can affect the proton NMRD even in
      the limit of weak coupling when (i) protons are coupled strongly and (ii) have
      spin-spin interactions of different strengths with the hetero-nuclei. We also
      show that by choosing the proper magnetic field strength, one can selectively
      transfer proton spin magnetization between spectral components of choice.

PMID- 22957578
TI  - Ultraviolet and visible Brillouin scattering study of viscous relaxation in 3
      methylpentane down to the glass transition.
AB  - Brillouin light scattering spectra from transverse and longitudinal acoustic
      waves in liquid and supercooled 3-methylpentane have been collected from room
      temperature down to 80 K, just above the glass transition. Spectra at different
      wave vectors have been obtained using 532 nm and 266 nm excitation. We found
      evidence of a shear relaxation with a characteristic time of 100 s at the glass
      transition which only partly accounts for the relaxation observed in the
      propagation and attenuation of the longitudinal modes. The inclusion of a
      relaxing bulk viscosity contribution with a relaxation time of the order of 10(2)
      ns at the glass transition is found to adequately reproduce the experimental data
      including transient grating data at a much lower frequency. A consistent picture
      of relaxed shear and bulk moduli as a function of temperature is derived. These
      two quantities are found to be related by a linear relation suggesting that a
      Cauchy-like relation holds also above the glass transition.

PMID- 22957579
TI  - Single particle force distributions in simple fluids.
AB  - The distribution function, W(F), of the magnitude of the net force, F, on
      particles in simple fluids is considered, which follows on from our previous
      publication [A. C. Branka, D. M. Heyes, and G. Rickayzen, J. Chem. Phys. 135,
      164507 (2011)] concerning the pair force, f, distribution function, P(f), which
      is expressible in terms of the radial distribution function. We begin by
      discussing the force on an impurity particle in an otherwise pure fluid but later
      specialize to the pure fluid, which is studied in more detail. An approximate
      formula, expected to be valid asymptotically, for W(F) referred to as, W(1)(F) is
      derived by taking into account only binary spatial correlations in the fluid. It
      is found that W(1)(F) = P(f). Molecular dynamics simulations of W for the inverse
      power (IP) and Lennard-Jones potential fluids show that, as expected, W(F) and
      P(f) agree well in the large force limit for a wide range of densities and
      potential forms. The force at which the maximum in W(F) occurs for the IP fluids
      follows a different algebraic dependence with density in low and high density
      domains of the equilibrium fluid. Other characteristic features in the force
      distribution functions also exhibit the same trends. An exact formula is derived
      relating W(F) to P(x)(F(x)), the distribution function of the x-cartesian
      components of the net force, F(x), on a particle. W(F) and P(x)(F(x)) have the
      same analytical forms (apart from constants) in the low and high force limits.

PMID- 22957580
TI  - High resolution electron energy loss spectroscopy of clean and hydrogen covered
      Si(001) surfaces: first principles calculations.
AB  - Surface phonons, conductivities, and loss functions are calculated for
      reconstructed (2*1), p(2*2) and c(4*2) clean Si(001) surfaces, and (2*1) H and D
      covered Si(001) surfaces. Surface conductivities perpendicular to the surface are
      significantly smaller than conductivities parallel to the surface. The surface
      loss function is compared to high resolution electron energy loss measurements.
      There is good agreement between calculated loss functions and experiment for H
      and D covered surfaces. However, agreement between experimental data from
      different groups and between theory and experiment is poor for clean Si(001)
      surfaces. Formalisms for calculating electron energy loss spectra are reviewed
      and the mechanism of electron energy losses to surface vibrations is discussed.

PMID- 22957581
TI  - Anisotropy in the crystal growth of hexagonal ice, I(h).
AB  - Growth of ice crystals has attracted attention because ice and water are
      ubiquitous in the environment and play critical roles in natural processes.
      Hexagonal ice, I(h), is the most common form of ice among 15 known crystalline
      phases of ice. In this work we report the results of an extensive and systematic
      molecular dynamics study of the temperature dependence of the crystal growth on
      the three primary crystal faces of hexagonal ice, the basal {0001} face, the
      prism {1010} face, and the secondary prism {1120} face, utilizing the TIP4P-2005
      water model. New insights into the nature of its anisotropic growth are
      uncovered. It is demonstrated that the ice growth is indeed anisotropic; the
      growth and melting of the basal face are the slowest of the three faces, its
      maximum growth rates being 31% and 43% slower, respectively, than those of the
      prism and the secondary prism faces. It is also shown that application of
      periodic boundary conditions can lead to varying size effect for different
      orientations of an ice crystal caused by the anisotropic physical properties of
      the crystal, and results in measurably different thermodynamic melting
      temperatures in three systems of similar, yet moderate, size. Evidence obtained
      here provides the grounds on which to clarify the current understanding of ice
      growth on the secondary prism face of ice. We also revisit the effect of the
      integration time step on the crystal growth of ice in a more thorough and
      systematic way. Careful evaluation demonstrates that increasing the integration
      time step size measurably affects the free energy of the bulk phases and shifts
      the temperature dependence of the growth rate curve to lower temperatures by
      approximately 1 K when the step is changed from 1 fs to 2 fs, and by 3 K when 3
      fs steps are used. A thorough investigation of the numerical aspects of the
      simulations exposes important consequences of the simulation parameter choices
      upon the delicate dynamic balance that is involved in ice crystal growth.

PMID- 22957582
TI  - Inelastic tunneling spectroscopy of gold-thiol and gold-thiolate interfaces in
      molecular junctions: the role of hydrogen.
AB  - It is widely believed that when a molecule with thiol (S-H) end groups bridges a
      pair of gold electrodes, the S atoms bond to the gold and the thiol H atoms
      detach from the molecule. However, little is known regarding the details of this
      process, its time scale, and whether molecules with and without thiol hydrogen
      atoms can coexist in molecular junctions. Here, we explore theoretically how
      inelastic tunneling spectroscopy (IETS) can shed light on these issues. We
      present calculations of the geometries, low bias conductances, and IETS of
      propanedithiol and propanedithiolate molecular junctions with gold electrodes. We
      show that IETS can distinguish between junctions with molecules having no, one,
      or two thiol hydrogen atoms. We find that in most cases, the single-molecule
      junctions in the IETS experiment of Hihath et al. [Nano Lett. 8, 1673 (2008)] had
      no thiol H atoms, but that a molecule with a single thiol H atom may have bridged
      their junction occasionally. We also consider the evolution of the IETS spectrum
      as a gold STM tip approaches the intact S-H group at the end of a molecule bound
      at its other end to a second electrode. We predict the frequency of a vibrational
      mode of the thiol H atom to increase by a factor ~2 as the gap between the tip
      and molecule narrows. Therefore, IETS should be able to track the approach of the
      tip towards the thiol group of the molecule and detect the detachment of the
      thiol H atom from the molecule when it occurs.

PMID- 22957583
TI  - Free-energy based pair-additive potentials for bulk Ni-Al systems: application to
      study Ni-Al reactive alloying.
AB  - We present new numerical pair-additive Al, Ni, and Al-Ni potentials by force
      matching (FM) ionic force and virial data from single (bulk liquid) phase ab
      initio molecular dynamics (MD) simulations using the Born-Oppenheimer method. The
      potentials are represented by piece-wise functions (splines) and, therefore, are
      not constrained to a particular choice of analytical functional form. The FM
      method with virial constraint naturally yields a potential which maps out the
      ionic free-energy surface of the reference ensemble. To further improve the free
      energetics of the FM ensemble, the FM procedure is modified to bias the
      potentials to reproduce the experimental melting temperatures of the reference
      (FCC-Al, FCC-Ni, B2-NiAl) phases, the only macroscopic data included in the
      fitting set. The performance of the resultant potentials in simulating bulk
      metallic phases is then evaluated. The new model is applied to perform MD
      simulations of self-propagating exothermic reaction in Ni-Al bilayers at P = 0-5
      GPa initiated at T = 1300 K. Consistent with experimental observations, the new
      model describes realistically a sequence of peritectic phase transformations
      throughout the reaction and at a realistic rate. The reaction proceeds through
      interlayer diffusion of Al and Ni atoms at the interface with formation of B2
      NiAl in the Al melt. Such material responses have, in the past, been proven to be
      difficult to observe with then-existing potentials.

PMID- 22957584
TI  - Half-metallicity in graphene nanoribbons with topological defects at edge.
AB  - We report first principles studies of zigzag edged graphene nanoribbons (ZGNR)
      with one edge partially covered by topological defects. With increasing coverage
      of an edge by pentagons and heptagons, which are two of the simplest topological
      defects possible in a graphenic lattice, ZGNRs evolve from a magnetic
      semiconductor to a ferromagnetic metal. This evolution can be intermediated by a
      narrow bandgap half-metallic phase, upon suitable concentration and conformation
      of defects at the edge. Spin-frustration induced by topological defects lead to
      substantial lowering of magnetic ordering and localization of defect-states in
      the vicinity of the defects. Dispersion of bands constituted by the defect-states
      within the bandgap of the corresponding unmodified ZGNR, leads to availability of
      energy windows for spin-polarized electron transport. Driven primarily by
      exchange interactions, the energy window for transport of electrons near Fermi
      energy, is consistently wider and more prevalent for the minority spin, in the
      entire class of ZGNRs with discontinuous patches of topological defects at an
      edge. Such defects have been widely predicted and observed to be naturally
      present at the interfaces in polycrystalline graphene, and can even be formed
      through chemical and physical processes. Our approach thus may lead to a feasible
      strategy to manifest workable half-metallicity in ZGNRs without involving non
      carbon dopants or functional groups.

PMID- 22957585
TI  - Ultrafast vibrational dynamics of water at a charged interface revealed by two
      dimensional heterodyne-detected vibrational sum frequency generation.
AB  - Two-dimensional heterodyne-detected vibrational sum frequency generation (2D HD
      VSFG) spectroscopy is performed for an aqueous interface for the first time. The
      2D HD-VSFG spectra in the OH stretch region are obtained from a positively
      charged surfactant/water interface with isotopically diluted water (HOD/D(2)O) to
      reveal the femtosecond vibrational dynamics of water at the charged interface.
      The 2D HD-VSFG spectrum is diagonally elongated immediately after
      photoexcitation, clearly demonstrating inhomogeneity in the interfacial water.
      This elongation almost disappears at 300 fs owing to the spectral diffusion.
      Interestingly, the 2D HD-VSFG spectrum at the 0 fs shows an oppositely asymmetric
      shape to the corresponding 2D IR spectrum in bulk water: The bandwidth of the
      bleach signal gets narrower when the pump wavenumber becomes higher. This
      suggests that the dynamics and mechanism of the hydrogen bond rearrangement at
      the charged interface are significantly different from those in bulk water.

PMID- 22957586
TI  - On the early stage of aluminum oxidation: an extraction mechanism via oxygen
      cooperation.
AB  - We propose a barrierless mechanism for describing the oxidation of Al(111) in
      which oxygen atoms located on the outer surface extract aluminum atoms of the
      surface layers through local cooperation of other pre-adsorbed oxygen atoms. We
      show the details of this complex chemical process that kinetically competes with
      the non-destructive formation of an oxygen monolayer onto the Al surface, thus
      elucidating the initial aluminum oxidation regime. We demonstrate that further
      stripping of the complete surface Al layer is consistent with both (i) the
      formation of a defective alumina structure and (ii) an oxide capping layer
      preventing further oxidation at low temperature.

PMID- 22957587
TI  - Water dissociation on Cu(111): effects of molecular orientation, rotation, and
      vibration on reactivity.
AB  - Three-dimensional time-dependent quantum mechanical method has been used to study
      the influence of orientation, rotation, and vibration on the dissociation of
      water molecule on Cu(111) surface, using London-Eyring-Polanyi-Sato potential
      energy surface. Our calculations show that dependency of dissociation probability
      on the initial orientation of the molecule changes with the vibrational state of
      the molecule. It has also been found that for v(0) = 0 and 1, where v(0) stands
      for the vibrational state of the pseudo diatomic HO-H, the rotational excitation
      of the molecule increases the reactivity, whereas for v(0) = 2, the rotational
      excitation of the molecule decreases the reactivity. Vibrational excitation of
      the molecule greatly enhances the dissociation probability.

PMID- 22957588
TI  - Effect of solvent quality on the dispersibility of polymer-grafted spherical
      nanoparticles in polymer solutions.
AB  - In this work, lattice-based self consistent field theory is used to study the
      structural properties of individual polymer-grafted spherical nanopartices and
      particle-particle interactions in polymer melts and solutions under variable
      solvent conditions. Our study has focused on the depth of the minimum in the
      potential of mean force between the two brush-coated nanoparticles, if such a
      minimum occurs, and we have also addressed the corresponding radial density
      profiles of free and grafted chains around a single nanoparticle, in an attempt
      to clarify the extent of correlation between the depth of the minimum, W(min),
      and the parameter delta characterizing the interpenetration between the profiles
      of free and grafted chains. Although one cannot establish a simple one-to-one
      correspondence between W(min) and delta, we do find common trends, in particular,
      if the solvent conditions for free and grafted chains differ: varying the volume
      fraction of the free chains, delta typically exhibits a broad minimum,
      corresponding to a region where the magnitude of W(min) exceeds thermal energy
      k(B)T, leading to particle aggregation.

PMID- 22957589
TI  - Molecular dynamics study of free energy of transfer of alcohol and amine from
      water phase to the micelle by thermodynamic integration method.
AB  - Free energy of transfer of methylamine, octylamine, methanol, and octanol from
      water phase to sodium dodecyl sulfate (SDS) micelle has been calculated using
      thermodynamic integration method combined with molecular dynamics calculations.
      Together with the results for alkanes obtained in our previous study [K.
      Fujimoto, N. Yoshii, and S. Okazaki, J. Chem. Phys. 133, 074511 (2010)], the
      effect of polar group on the partition of hydrophilic solutes between water phase
      and the micelle has been investigated in detail at a molecular level. The
      calculations showed that the molecules with octyl group are more stable in the
      SDS micelle than in the water phase due to their hydrophobicity of long alkyl
      chain. In contrast, methanol and methylamine are stable in the water phase as
      well as in the micelle because of their high hydrophilicity. The spatial
      distribution of methylamine, octylamine, methanol, and octanol has also been
      evaluated as a function of the distance, R, from the center of mass of SDS
      micelle to the solutes. The distribution shows that the methylamine molecule is
      adsorbed on the SDS micelle surface, while the methanol molecule is delocalized
      among the whole system, i.e., in the water phase, on the surface of the micelle,
      and in the hydrophobic core of the micelle. The octylamine and octanol molecules
      are solubilized in the SDS micelle with palisade layer structure and are not
      found in the water phase.

PMID- 22957590
TI  - Theory and simulation of organic solar cell model compounds: how packing and
      morphology determine the electronic conductivity.
AB  - We approach the electronic conductivity of simple models of organic solar cells
      containing linear and branched alphaalpha'-oligothiophenes and
      buckminsterfullerene. Close-packed model geometries are generated using a Monte
      Carlo method, this procedure is verified making use of an analogue model. The
      electronic structure is described by an extended Su-Schrieffer-Heeger
      Hamiltonian, the resulting potential energy surfaces relevant to charge transfer
      can be analyzed using Marcus' theory, leading to local and--via Kirchhoff's rule-
      global conductivities for uniform oligothiophene and fullerene systems and their
      mixtures. Dense fullerene systems or subsystems always exhibit a conductivity in
      excess of 100 S/cm. In contrast, oligothiophenes show a comparable conductivity
      only for uniform, well-ordered arrangements of layers. Branched oligomers show
      only a slight improvement over linear oligothiophenes. Our results support the
      bulk heterojunction approach as a design principle of organic solar cells from a
      theoretical perspective.

PMID- 22957591
TI  - Coarse-graining MARTINI model for molecular-dynamics simulations of the wetting
      properties of graphitic surfaces with non-ionic, long-chain, and T-shaped
      surfactants.
AB  - We report on a molecular dynamics investigation of the wetting properties of
      graphitic surfaces by various solutions at concentrations 1-8 wt. % of
      commercially available non-ionic surfactants with long hydrophilic chains, linear
      or T-shaped. These are surfactants of length up to 160 A. It turns out that
      molecular dynamics simulations of such systems ask for a number of solvent
      particles that can be reached without seriously compromising computational
      efficiency only by employing a coarse-grained model. The MARTINI force field with
      polarizable water offers a framework particularly suited for the parameterization
      of our systems. In general, its advantages over other coarse-grained models are
      the possibility to explore faster long time scales and the wider range of
      applicability. Although the accuracy is sometimes put under question, the results
      for the wetting properties by pure water are in good agreement with those for the
      corresponding atomistic systems and theoretical predictions. On the other hand,
      the bulk properties of various aqueous surfactant solutions indicate that the
      micellar formation process is too strong. For this reason, a typical experimental
      configuration is better approached by preparing the droplets with the surfactants
      arranged in the initial state in the vicinity of contact line. Cross-comparisons
      are possible and illuminating, but equilibrium contact angles as obtained from
      simulations overestimate the experimental results. Nevertheless, our findings can
      provide guidelines for the preliminary assessment and screening of surfactants.
      Most importantly, it is found that the wetting properties mainly depend on the
      length and apolarity of the hydrophobic tail, for linear surfactants, and the
      length of the hydrophilic headgroup for T-shaped surfactants. Moreover, the T
      shaped topology appears to favor the adsorption of surfactants onto the graphitic
      surface and faster spreading.

PMID- 22957592
TI  - Mean-field theory of the phase diagram of ultrasoft, oppositely charged polyions
      in solution.
AB  - We investigate the phase separation of the "ultrasoft restricted primitive model"
      (URPM), a coarse-grained representation of oppositely charged, interpenetrating
      polyelectrolytes, within a mean-field description based on the "chemical
      picture." The latter distinguishes between free ions and dimers of oppositely
      charged ions (Bjerrum pairs) which are in chemical equilibrium governed by a law
      of mass action. Interactions between ions, and between ions and dimers are
      treated within linearized Poisson-Boltzmann theory, at four levels of
      approximation corresponding to increasingly refined descriptions of the
      interactions. The URPM is found to phase separate into a dilute phase of dimers,
      and a concentrated phase of mostly free (unpaired) ions below a critical
      temperature T(c). The phase diagram differs, however, considerably from the
      predictions of recent simulations; T(c) is about three times higher, and the
      critical density is much lower than the corresponding simulation data [D.
      Coslovich, J. P. Hansen, and G. Kahl, Soft Matter 7, 1690 (2011)]. Possible
      reasons for this unexpected failure of mean-field theory are discussed. The
      Kirkwood line, separating the regimes of monotonically decaying and damped
      oscillatory decay of the charge-charge correlation function at large distances is
      determined within the random phase approximation.

PMID- 22957593
TI  - Micro-structure evolution of wall based crystals after casting of model
      suspensions as obtained from Bragg microscopy.
AB  - Growth of heterogeneously nucleated, wall based crystals plays a major role in
      determining the micro-structure during melt casting. This issue is here addressed
      using a model system of charged colloidal spheres in deionized aqueous suspension
      observed by Bragg microscopy which is a combination of light scattering and
      microscopy. We examine the evolution of the three-dimensional size, shape, and
      orientation of twin domains in monolithic crystals growing from two opposing
      planar walls into a meta-stable (shear-) melt. At each wall crystal orientation
      and twinning emerges during nucleation with small domains. During growth these
      widen and merge. From image analysis we observe the lateral coarsening velocities
      to follow a power law behaviour L(XY) ? t(1/2) as long as the vertical growth
      continues at constant speed. Lateral coarsening terminates upon intersection of
      the two solids and hardly any further ripening is seen. Initial lateral
      coarsening velocities show a Wilson Frenkel type dependence on the melt meta
      stability.

PMID- 22957594
TI  - Effect of grafting on nanoparticle segregation in polymer/nanoparticle blends
      near a substrate.
AB  - Nanoparticles in polymer films have shown the tendency to migrate to the
      substrate due to an entropic-based attractive depletion interaction between the
      particles and the substrate. It is also known that polymer-grafted nanoparticles
      show better dispersion in a polymer matrix. Here, molecular dynamics simulations
      are employed to study the effect of grafting on the nanoparticle segregation to
      the substrate. The nanoparticles were modeled as spheres and the polymers as bead
      spring chains. The polymers of the grafts and the matrix are identical in nature.
      For a purely repulsive system, the nanoparticle density near the surface was
      found to decrease as the length of grafted chains and the number of grafts
      increased and in the bulk, the nanoparticles are well-dispersed. Whereas, in case
      of attractive systems with interparticle interactions on the order of thermal
      energy, the nanoparticles segregated to the substrate even more strongly,
      essentially forming clusters on the wall and in the bulk. However, due to the
      presence of grafted chains on the nanoparticles, the clusters formed in the bulk
      are structurally anisotropic. The effect of grafts on nanoparticle segregation to
      the surface was found to be qualitatively similar to the purely repulsive case.

PMID- 22957595
TI  - Radiowave dielectric investigation of water confined in channels of carbon
      nanotubes.
AB  - Structure and dynamics of water confined in channels of diameter of few nanometer
      in size strongly differ from the ones of water in the bulk phase. Here, we
      present radiowave dielectric relaxation measurements on water-filled single
      walled carbon nanotubes, with the aim of highlighting some aspects on the
      molecular electric dipole organization of water responding to high spatial
      confinement in a hydrophobic environment. The observed dielectric spectra,
      resulting into two contiguous relaxation processes, allow us to separate the
      confined water in the interior of the nanotubes from external water, providing
      support for the existence in the confinement region of water domains held
      together by hydrogen bonds. Our results, based on the deconvolution of the
      dielectric spectra due to the presence of a bulk and a confined water phase,
      furnish a significantly higher Kirkwood correlation factor, larger than the one
      of water in bulk phase, indicating a strong correlation between water molecules
      inside nanotubes, not seen in bulk water.

PMID- 22957596
TI  - New method for determining size of critical nucleus of fibril formation of
      polypeptide chains.
AB  - A new method for determining the size of critical nucleus of fibril formation of
      polypeptide chains is proposed. Based on the hypothesis that the fibril grows by
      addition of a nascent peptide to the preformed template, the nucleus size N(c) is
      defined as the number of forming template peptides above which the time to add a
      new monomer becomes independent of the template size. Using lattice models one
      can show that our method and the standard method which is based on calculation of
      the free energy, provide the same result for N(c).

PMID- 22957598
TI  - Point/counterpoint: computer-aided detection should be used routinely to assist
      screening mammogram interpretation.

PMID- 22957599
TI  - Validating plastic scintillation detectors for photon dosimetry in the radiologic
      energy range.
AB  - PURPOSE: Photon dosimetry in the kilovolt (kV) energy range represents a major
      challenge for diagnostic and interventional radiology and superficial therapy.
      Plastic scintillation detectors (PSDs) are potentially good candidates for this
      task. This study proposes a simple way to obtain accurate correction factors to
      compensate for the response of PSDs to photon energies between 80 and 150 kVp.
      The performance of PSDs is also investigated to determine their potential
      usefulness in the diagnostic energy range. METHODS: A 1-mm-diameter, 10-mm-long
      PSD was irradiated by a Therapax SXT 150 unit using five different beam qualities
      made of tube potentials ranging from 80 to 150 kVp and filtration thickness
      ranging from 0.8 to 0.2 mmAl + 1.0 mmCu. The light emitted by the detector was
      collected using an 8-m-long optical fiber and a polychromatic photodiode, which
      converted the scintillation photons to an electrical current. The PSD response
      was compared with the reference free air dose rate measured with a calibrated
      Farmer NE2571 ionization chamber. PSD measurements were corrected using spectra
      weighted corrections, accounting for mass energy-absorption coefficient
      differences between the sensitive volumes of the ionization chamber and the PSD,
      as suggested by large cavity theory (LCT). Beam spectra were obtained from x-ray
      simulation software and validated experimentally using a CdTe spectrometer.
      Correction factors were also obtained using Monte Carlo (MC) simulations. Percent
      depth dose (PDD) measurements were compensated for beam hardening using the LCT
      correction method. These PDD measurements were compared with uncorrected PSD
      data, PDD measurements obtained using Gafchromic films, Monte Carlo simulations,
      and previous data. RESULTS: For each beam quality used, the authors observed an
      increase of the energy response with effective energy when no correction was
      applied to the PSD response. Using the LCT correction, the PSD response was
      almost energy independent, with a residual 2.1% coefficient of variation (COV)
      over the 80-150-kVp energy range. Monte Carlo corrections reduced the COV to 1.4%
      over this energy range. All PDD measurements were in good agreement with one
      another except for the uncorrected PSD data, in which an over-response was
      observed with depth (13% at 10 cm with a 100 kVp beam), showing that beam
      hardening had a non-negligible effect on the PSD response. A correction based on
      LCT compensated very well for this effect, reducing the over-response to 3%.
      CONCLUSION: In the diagnostic energy range, PSDs show high-energy dependence,
      which can be corrected using spectra-weighted mass energy-absorption
      coefficients, showing no considerable sign of quenching between these energies.
      Correction factors obtained by Monte Carlo simulations confirm that the
      approximations made by LCT corrections are valid. Thus, PSDs could be useful for
      real-time dosimetry in radiology applications.

PMID- 22957600
TI  - Ideal-observer detectability in photon-counting differential phase-contrast
      imaging using a linear-systems approach.
AB  - PURPOSE: To provide a cascaded-systems framework based on the noise-power
      spectrum (NPS), modulation transfer function (MTF), and noise-equivalent number
      of quanta (NEQ) for quantitative evaluation of differential phase-contrast
      imaging (Talbot interferometry) in relation to conventional absorption contrast
      under equal-dose, equal-geometry, and, to some extent, equal-photon-economy
      constraints. The focus is a geometry for photon-counting mammography. METHODS:
      Phase-contrast imaging is a promising technology that may emerge as an
      alternative or adjunct to conventional absorption contrast. In particular, phase
      contrast may increase the signal-difference-to-noise ratio compared to absorption
      contrast because the difference in phase shift between soft-tissue structures is
      often substantially larger than the absorption difference. We have developed a
      comprehensive cascaded-systems framework to investigate Talbot interferometry,
      which is a technique for differential phase-contrast imaging. Analytical
      expressions for the MTF and NPS were derived to calculate the NEQ and a task
      specific ideal-observer detectability index under assumptions of linearity and
      shift invariance. Talbot interferometry was compared to absorption contrast at
      equal dose, and using either a plane wave or a spherical wave in a conceivable
      mammography geometry. The impact of source size and spectrum bandwidth was
      included in the framework, and the trade-off with photon economy was investigated
      in some detail. Wave-propagation simulations were used to verify the analytical
      expressions and to generate example images. RESULTS: Talbot interferometry
      inherently detects the differential of the phase, which led to a maximum in NEQ
      at high spatial frequencies, whereas the absorption-contrast NEQ decreased
      monotonically with frequency. Further, phase contrast detects differences in
      density rather than atomic number, and the optimal imaging energy was found to be
      a factor of 1.7 higher than for absorption contrast. Talbot interferometry with a
      plane wave increased detectability for 0.1-mm tumor and glandular structures by a
      factor of 3-4 at equal dose, whereas absorption contrast was the preferred method
      for structures larger than ~0.5 mm. Microcalcifications are small, but differ
      from soft tissue in atomic number more than density, which is favored by
      absorption contrast, and Talbot interferometry was barely beneficial at all
      within the resolution limit of the system. Further, Talbot interferometry favored
      detection of "sharp" as opposed to "smooth" structures, and discrimination tasks
      by about 50% compared to detection tasks. The technique was relatively
      insensitive to spectrum bandwidth, whereas the projected source size was more
      important. If equal photon economy was added as a restriction, phase-contrast
      efficiency was reduced so that the benefit for detection tasks almost vanished
      compared to absorption contrast, but discrimination tasks were still improved
      close to a factor of 2 at the resolution limit. CONCLUSIONS: Cascaded-systems
      analysis enables comprehensive and intuitive evaluation of phase-contrast
      efficiency in relation to absorption contrast under requirements of equal dose,
      equal geometry, and equal photon economy. The benefit of Talbot interferometry
      was highly dependent on task, in particular detection versus discrimination
      tasks, and target size, shape, and material. Requiring equal photon economy
      weakened the benefit of Talbot interferometry in mammography.

PMID- 22957601
TI  - A database for estimating organ dose for coronary angiography and brain perfusion
      CT scans for arbitrary spectra and angular tube current modulation.
AB  - PURPOSE: The purpose of this study was to develop a database for estimating organ
      dose in a voxelized patient model for coronary angiography and brain perfusion CT
      acquisitions with any spectra and angular tube current modulation setting. The
      database enables organ dose estimation for existing and novel acquisition
      techniques without requiring Monte Carlo simulations. METHODS: The study
      simulated transport of monoenergetic photons between 5 and 150 keV for 1000
      projections over 360 degrees  through anthropomorphic voxelized female chest and
      head (0 degrees  and 30 degrees  tilt) phantoms and standard head and body CTDI
      dosimetry cylinders. The simulations resulted in tables of normalized dose
      deposition for several radiosensitive organs quantifying the organ dose per
      emitted photon for each incident photon energy and projection angle for coronary
      angiography and brain perfusion acquisitions. The values in a table can be
      multiplied by an incident spectrum and number of photons at each projection angle
      and then summed across all energies and angles to estimate total organ dose.
      Scanner-specific organ dose may be approximated by normalizing the database
      estimated organ dose by the database-estimated CTDI(vol) and multiplying by a
      physical CTDI(vol) measurement. Two examples are provided demonstrating how to
      use the tables to estimate relative organ dose. In the first, the change in
      breast and lung dose during coronary angiography CT scans is calculated for
      reduced kVp, angular tube current modulation, and partial angle scanning
      protocols relative to a reference protocol. In the second example, the change in
      dose to the eye lens is calculated for a brain perfusion CT acquisition in which
      the gantry is tilted 30 degrees  relative to a nontilted scan. RESULTS: Our
      database provides tables of normalized dose deposition for several radiosensitive
      organs irradiated during coronary angiography and brain perfusion CT scans.
      Validation results indicate total organ doses calculated using our database are
      within 1% of those calculated using Monte Carlo simulations with the same
      geometry and scan parameters for all organs except red bone marrow (within 6%),
      and within 23% of published estimates for different voxelized phantoms. Results
      from the example of using the database to estimate organ dose for coronary
      angiography CT acquisitions show 2.1%, 1.1%, and -32% change in breast dose and
      2.1%, -0.74%, and 4.7% change in lung dose for reduced kVp, tube current
      modulated, and partial angle protocols, respectively, relative to the reference
      protocol. Results show -19.2% difference in dose to eye lens for a tilted scan
      relative to a nontilted scan. The reported relative changes in organ doses are
      presented without quantification of image quality and are for the sole purpose of
      demonstrating the use of the proposed database. CONCLUSIONS: The proposed
      database and calculation method enable the estimation of organ dose for coronary
      angiography and brain perfusion CT scans utilizing any spectral shape and angular
      tube current modulation scheme by taking advantage of the precalculated Monte
      Carlo simulation results. The database can be used in conjunction with image
      quality studies to develop optimized acquisition techniques and may be
      particularly beneficial for optimizing dual kVp acquisitions for which numerous
      kV, mA, and filtration combinations may be investigated.

PMID- 22957602
TI  - Equations for CT dose calculations on axial lines based on the principle of
      symmetry.
AB  - PURPOSE: Radiation dose from CT examination depends on the position relative to
      the irradiated region in the longitudinal direction. The objective of this work
      is to present a mechanism for calculating dose at any point on a line parallel to
      the axis of rotation. METHODS: In a medium that is uniform in the z direction,
      the cumulative dose at the midpoint D(L)(0) of the irradiated length (L)
      increases with L until the equilibrium dose (D(eq)) is reached. Using the
      approach to equilibrium function, H(L) = D(L)(0)/D(eq), the authors formulated
      equations for calculating dose at an arbitrary point on an axial line. RESULTS:
      Dose calculation examples are presented for multidetector CT (MDCT) and micro-CT.
      CONCLUSIONS: The new equations are suited for any functional form of H(L), and
      can be used for dose evaluations in MDCT, micro-CT, cone-beam CT, and other cases
      with media that are approximately uniform along the z direction.

PMID- 22957603
TI  - The use of zeolites to generate PET phantoms for the validation of quantification
      strategies in oncology.
AB  - PURPOSE: In recent years, segmentation algorithms and activity quantification
      methods have been proposed for oncological (18)F-fluorodeoxyglucose (FDG) PET. A
      full assessment of these algorithms, necessary for a clinical transfer, requires
      a validation on data sets provided with a reliable ground truth as to the imaged
      activity distribution, which must be as realistic as possible. The aim of this
      work is to propose a strategy to simulate lesions of uniform uptake and irregular
      shape in an anthropomorphic phantom, with the possibility to easily obtain a
      ground truth as to lesion activity and borders. METHODS: Lesions were simulated
      with samples of clinoptilolite, a family of natural zeolites of irregular shape,
      able to absorb aqueous solutions of (18)F-FDG, available in a wide size range,
      and nontoxic. Zeolites were soaked in solutions of (18)F-FDG for increasing times
      up to 120 min and their absorptive properties were characterized as function of
      soaking duration, solution concentration, and zeolite dry weight. Saturated
      zeolites were wrapped in Parafilm, positioned inside an Alderson thorax-abdomen
      phantom and imaged with a PET-CT scanner. The ground truth for the activity
      distribution of each zeolite was obtained by segmenting high-resolution finely
      aligned CT images, on the basis of independently obtained volume measurements.
      The fine alignment between CT and PET was validated by comparing the CT-derived
      ground truth to a set of zeolites' PET threshold segmentations in terms of Dice
      index and volume error. RESULTS: The soaking time necessary to achieve saturation
      increases with zeolite dry weight, with a maximum of about 90 min for the largest
      sample. At saturation, a linear dependence of the uptake normalized to the
      solution concentration on zeolite dry weight (R(2) = 0.988), as well as a uniform
      distribution of the activity over the entire zeolite volume from PET imaging were
      demonstrated. These findings indicate that the (18)F-FDG solution is able to
      saturate the zeolite pores and that the concentration does not influence the
      distribution uniformity of both solution and solute, at least at the trace
      concentrations used for zeolite activation. An additional proof of uniformity of
      zeolite saturation was obtained observing a correspondence between uptake and
      adsorbed volume of solution, corresponding to about 27.8% of zeolite volume. As
      to the ground truth for zeolites positioned inside the phantom, the segmentation
      of finely aligned CT images provided reliable borders, as demonstrated by a mean
      absolute volume error of 2.8% with respect to the PET threshold segmentation
      corresponding to the maximum Dice. CONCLUSIONS: The proposed methodology allowed
      obtaining an experimental phantom data set that can be used as a feasible tool to
      test and validate quantification and segmentation algorithms for PET in oncology.
      The phantom is currently under consideration for being included in a benchmark
      designed by AAPM TG211, which will be available to the community to evaluate PET
      automatic segmentation methods.

PMID- 22957604
TI  - The effect of copper conversion plates on low-Z target image quality.
AB  - PURPOSE: Common electronic portal imaging devices (EPIDs) contain a 1.0 mm copper
      conversion plate to increase detection efficiency of a therapeutic megavoltage
      spectrum. When used in imaging with a photon beam generated with a low atomic
      number (Z) target, the conversion plate attenuates a substantial proportion of
      photons in the diagnostic range, thereby reducing the achievable image quality.
      In this work, we measure directly dependence on low-Z target image quality as a
      function of copper plate thickness, for both planar imaging and cone beam
      computed tomography (CBCT). METHODS: Monte Carlo modeling was used to quantify
      changes to the diagnostic spectrum and detector response for low-Z target beams
      generated with either 2.35 or 7.00 MeV electrons incident on a carbon target.
      Planar contrast-to-noise ratio (CNR) and spatial resolution measurements were
      made as a function of copper thickness. CNR measurements were made for CBCT
      imaging as a function of dose both with and without the copper plate present in
      the EPID. RESULTS: The presence of copper in the EPID decreased the diagnostic
      photon population by up to 20% and suppressed the peak detector response (dose
      deposited in the scintillator) at 60 keV by a factor of 6.4. Planar CNR was
      increased by a factor ranging from 1.4 to 4.0, depending on the material imaged,
      with no copper present compared to a standard 1.0 mm thickness. Planar spatial
      resolution was only slightly degraded with increasing copper thickness. Increases
      in CBCT image CNR ranged from a factor of 1.3-2.1 with the copper plate removed.
      CONCLUSIONS: It is possible to increase the proportion of photons in the
      diagnostic energy range (25 keV-150 keV) reaching the phosphor screen by as much
      as 20% when removing the copper conversion plate. This results in significant
      increases of planar and CBCT image CNR. Consequently, we suggest that the copper
      conversion plate be removed from the EPID when used for low-Z target planar or
      CBCT imaging.

PMID- 22957605
TI  - A phantom for testing of 4D-CT for radiotherapy of small lesions.
AB  - PURPOSE: The use of time-resolved four-dimensional computed tomography (4D-CT) in
      radiotherapy requires strict quality assurance to ensure the accuracy of motion
      management protocols. The aim of this work was to design and test a phantom
      capable of large amplitude motion for use in 4D-CT, with particular interest in
      small lesions typical for stereotactic body radiotherapy. METHODS: The phantom of
      "see-saw" design is light weight, capable of including various sample materials
      and compatible with several surrogate marker signal acquisition systems. It is
      constructed of polymethylmethacrylate (Perspex) and its movement is controlled
      via a dc motor and drive wheel. It was tested using two CT scanners with
      different 4D acquisition methods: the Philips Brilliance Big Bore CT (helical
      scan, pressure belt) and a General Electric Discovery STE PET/CT (axial scan,
      infrared marker). Amplitudes ranging from 1.5 to 6.0 cm and frequencies of up to
      40 cycles per minute were used to study the effect of motion on image quality.
      Maximum intensity projections (MIPs), as well as average intensity projections
      (AIPs) of moving objects were investigated and their quality dependence on the
      number of phase reconstruction bins assessed. RESULTS: CT number discrepancies
      between moving and stationary objects were found to have no systematic dependence
      on amplitude, frequency, or specific interphase variability. MIP-delineated
      amplitudes of motion were found to match physical phantom amplitudes to within 2
      mm for all motion scenarios tested. Objects undergoing large amplitude motions
      (>3.0 cm) were shown to cause artefacts in MIP and AIP projections when ten phase
      bins were assigned. This problem can be mitigated by increasing the number of
      phase bins in a 4D-CT scan. CONCLUSIONS: The phantom was found to be a suitable
      tool for evaluating the image quality of 4D-CT motion management technology, as
      well as providing a quality assurance tool for intercenter/intervendor testing of
      commercial 4D-CT systems. When imaging objects with large amplitudes, the
      completeness criterion described here indicates the number of phase bins required
      to prevent missing data in MIPs and AIPs. This is most relevant for small lesions
      undergoing large motions.

PMID- 22957606
TI  - A robust geometry estimation method for spiral, sequential and circular cone-beam
      micro-CT.
AB  - PURPOSE: The authors propose a novel method for misalignment estimation of micro
      CT scanners using an adaptive genetic algorithm. METHODS: The proposed algorithm
      is able to estimate the rotational geometry, the direction vector of table
      movement and the displacement between different imaging threads of a dual source
      or even multisource scanner. The calibration procedure does not rely on dedicated
      calibration phantoms and a sequence scan of a single metal bead is sufficient to
      geometrically calibrate the whole imaging system for spiral, sequential, and
      circular scan protocols. Dual source spiral and sequential scan protocols in
      micro-computed tomography result in projection data that-besides the source and
      detector positions and orientations-also require a precise knowledge of the table
      direction vector to be reconstructed properly. If those geometric parameters are
      not known accurately severe artifacts and a loss in spatial resolution appear in
      the reconstructed images as long as no geometry calibration is performed. The
      table direction vector is further required to ensure that consecutive volumes of
      a sequence scan can be stitched together and to allow the reconstruction of
      spiral data at all. RESULTS: The algorithm's performance is evaluated using
      simulations of a micro-CT system with known geometry and misalignment. To assess
      the quality of the algorithm in a real world scenario the calibration of a micro
      CT scanner is performed and several reconstructions with and without geometry
      estimation are presented. CONCLUSIONS: The results indicate that the algorithm
      successfully estimates all geometry parameters, misalignment artifacts in the
      reconstructed volumes vanish, and the spatial resolution is increased as can be
      shown by the evaluation of modulation transfer function measurements.

PMID- 22957607
TI  - Design and evaluation of the MAMMI dedicated breast PET.
AB  - PURPOSE: A breast dedicated positron emission tomography (PET) scanner has been
      developed based on monolithic LYSO crystals coupled to position sensitive
      photomultiplier tubes (PSPMTs). In this study, we describe the design of the PET
      system and report on its performance evaluation. METHODS: MAMMI is a breast PET
      scanner based on monolithic LYSO crystals. It consists of 12 compact modules with
      a transaxial field of view (FOV) of 170 mm in diameter and 40 mm axial FOV that
      translates to cover up to 170 mm. The patient lies down in a prone position that
      facilitates maximum breast elongation. Quantitative performance analysis of the
      calculated method for the attenuation correction specifically developed for
      MAMMI, and based on PET image segmentation, has also been conducted in this
      evaluation. In order to fully determine the MAMMI prototype's performance, we
      have adapted the measurements suggested for National Electrical Manufacturers
      Association (NEMA) NU 2-2007 and NU 4-2008 protocol tests, as they are defined
      for whole-body and small animal PET scanners, respectively. RESULTS: Spatial
      resolutions of 1.6, 1.8, and 1.9 mm were measured in the axial, radial, and
      tangential directions, respectively. A scatter fraction of 20.8% was obtained and
      the maximum NEC was determined to be 25 kcps at 44 MBq. The average sensitivity
      of the system was observed to be 1% for an energy window of (250 keV-750 keV) and
      a maximum absolute sensitivity of 1.8% was measured at the FOV center.
      CONCLUSIONS: The overall performance of the MAMMI reported on this evaluation
      quantifies its ability to produce high quality PET images. Spatial resolution
      values below 3 mm were measured in most of the FOV. Only the radial component of
      spatial resolution exceeds the 3 mm at radial positions larger than 60 mm. This
      study emphasizes the need for standardized testing methodologies for dedicated
      breast PET systems similar to NEMA standards for whole-body and small animal PET
      scanners.

PMID- 22957608
TI  - Quantifying the margin sharpness of lesions on radiological images for content
      based image retrieval.
AB  - PURPOSE: To develop a method to quantify the margin sharpness of lesions on CT
      and to evaluate it in simulations and CT scans of liver and lung lesions.
      METHODS: The authors computed two attributes of margin sharpness: the intensity
      difference between a lesion and its surroundings, and the sharpness of the
      intensity transition across the lesion boundary. These two attributes were
      extracted from sigmoid curves fitted along lines automatically drawn orthogonal
      to the lesion margin. The authors then represented the margin characteristics for
      each lesion by a feature vector containing histograms of these parameters. The
      authors created 100 simulated CT scans of lesions over a range of intensity
      difference and margin sharpness, and used the concordance correlation between the
      known parameter and the corresponding computed feature as a measure of
      performance. The authors also evaluated their method in 79 liver lesions (44
      patients: 23 M, 21 F, mean age 61) and 58 lung nodules (57 patients: 24 M, 33 F,
      mean age 66). The methodology presented takes into consideration the boundary of
      the liver and lung during feature extraction in clinical images to ensure that
      the margin feature do not get contaminated by anatomy other than the normal organ
      surrounding the lesions. For evaluation in these clinical images, the authors
      created subjective independent reference standards for pairwise margin sharpness
      similarity in the liver and lung cohorts, and compared rank orderings of
      similarity used using our sharpness feature to that expected from the reference
      standards using mean normalized discounted cumulative gain (NDCG) over all query
      images. In addition, the authors compared their proposed feature with two
      existing techniques for lesion margin characterization using the simulated and
      clinical datasets. The authors also evaluated the robustness of their features
      against variations in delineation of the lesion margin by simulating five types
      of deformations of the lesion margin. Equivalence across deformations was
      assessed using Schuirmann's paired two one-sided tests. RESULTS: In simulated
      images, the concordance correlation between measured gradient and actual gradient
      was 0.994. The mean (s.d.) and standard deviation NDCG score for the retrieval of
      K images, K = 5, 10, and 15, were 84% (8%), 85% (7%), and 85% (7%) for CT images
      containing liver lesions, and 82% (7%), 84% (6%), and 85% (4%) for CT images
      containing lung nodules, respectively. The authors' proposed method outperformed
      the two existing margin characterization methods in average NDCG scores over all
      K, by 1.5% and 3% in datasets containing liver lesion, and 4.5% and 5% in
      datasets containing lung nodules. Equivalence testing showed that the authors'
      feature is more robust across all margin deformations (p < 0.05) than the two
      existing methods for margin sharpness characterization in both simulated and
      clinical datasets. CONCLUSIONS: The authors have described a new image feature to
      quantify the margin sharpness of lesions. It has strong correlation with known
      margin sharpness in simulated images and in clinical CT images containing liver
      lesions and lung nodules. This image feature has excellent performance for
      retrieving images with similar margin characteristics, suggesting potential
      utility, in conjunction with other lesion features, for content-based image
      retrieval applications.

PMID- 22957609
TI  - Computer-aided lymph node segmentation in volumetric CT data.
AB  - PURPOSE: The purpose of this work was to develop and validate a computer-aided
      method for the 3D segmentation of lymph nodes in CT images. The proposed method
      can be utilized to facilitate applications like biopsy planning, image guided
      radiation treatment, or assessment of response to therapy. METHODS: An optimal
      surface finding based lymph node segmentation method was developed. Based on the
      approximate center point of a lymph node of interest, a graph is generated, which
      represents the local neighborhood around the lymph node at discrete locations
      (graph nodes). A cost function is calculated based on a weighted edge and region
      homogeneity term. By means of optimization, a surface-based segmentation of the
      lymph node is derived. In addition, an interactive segmentation refinement
      algorithm was developed, which allows the user to quickly correct segmentation
      errors, if needed. For assessment of segmentation accuracy, 111 lymph nodes of
      mediastinum, abdomen, head/neck, and axillary regions from 35 volumetric CT scans
      were utilized. For accuracy analysis, lymph nodes were divided into three test
      sets based on lymph node size and spatial resolution of the CT scan. The average
      lymph node size for test set I, II, and III was 1056, 1621, and 501 mm(3),
      respectively. Spatial resolution of test set II was lower than for test sets I
      and III. To generate an independent reference standard for comparison, all 111
      lymph nodes were segmented by an expert with a live wire approach. RESULTS: All
      test sets were segmented with the proposed approach. Out of the 111 lymph nodes,
      40 cases (36%) required computer-aided refinement of initial segmentation
      results. The refinement typically required 10 s per lymph node. The mean and
      standard deviation of the Dice coefficient for final segmentations was 0.847 +/-
      0.061, 0.836 +/- 0.058, and 0.809 +/- 0.070 for test sets I, II, and II,
      respectively. The average signed surface distance error was 0.023 +/- 0.171,
      0.394 +/- 0.189, and 0.001 +/- 0.146 mm for test sets I, II, and II,
      respectively. The time required for locating the approximate center point of a
      target lymph node in a scan, generating an initial OSF segmentation, and refining
      the segmentation, if needed, is typically less than one minute. CONCLUSIONS:
      Segmentation of lymph nodes in volumetric CT images is a challenging task due to
      partial volume effects, nearby strong edges, neighboring structures with similar
      intensity profiles and potentially inhomogeneous density of lymph nodes. The
      presented approach addresses many of these obstacles. In the majority of cases
      investigated, the initial segmentation method delivered results that did not
      require further processing. In addition, the computer-aided segmentation
      refinement framework was found to be effective in dealing with potentially
      occurring segmentation errors.

PMID- 22957610
TI  - Incorporation of treatment plan spatial and temporal dose patterns into a
      prostate intrafractional motion management strategy.
AB  - PURPOSE: Periodic MV/KV radiographs taken during volumetric modulated arc therapy
      (VMAT) for hypofractionated treatment provide guidance in intrafractional motion
      management. The choice of imaging frequency and timing are key components in
      delivering the desired dose while reducing associated overhead such as imaging
      dose, preparation, and processing time. In this project the authors propose a
      paradigm with imaging timing and frequency based on the spatial and temporal dose
      patterns of the treatment plan. METHODS: A number of control points are used in
      treatment planning to model VMAT delivery. For each control point, the
      sensitivity of individual target or organ-at-risk dose to motion can be
      calculated as the summation of dose degradations given the organ displacements
      along a number of possible motion directions. Instead of acquiring radiographs at
      uniform time intervals, MV/KV image pairs are acquired indexed to motion
      sensitivity. Five prostate patients treated via hypofractionated VMAT are
      included in this study. Intrafractional prostate motion traces from the database
      of an electromagnetic tracking system are used to retrospectively simulate the
      VMAT delivery and motion management. During VMAT delivery simulation patient
      position is corrected based on the radiographic findings via couch movement if
      target deviation violates a patient-specific 3D threshold. The violation rate
      calculated as the percentage of traces failing the clinical dose objectives after
      motion correction is used to evaluate the efficacy of this approach. RESULTS:
      Imaging indexed to a 10 s equitime interval and correcting patient position
      accordingly reduces the violation rate to 19.5% with intervention from 44.5%
      without intervention. Imaging indexed to the motion sensitivity further reduces
      the violation rate to 12.1% with the same number of images. To achieve the same
      5% violation rate, the imaging incidence can be reduced by 40% by imaging indexed
      to motion sensitivity instead of time. CONCLUSIONS: The simulation results
      suggest that image scheduling according to the characteristics of the treatment
      plan can improve the efficiency of intrafractional motion management. Using such
      a technique, the accuracy of delivered dose during image-guided hypofractionated
      VMAT treatment can be improved.

PMID- 22957611
TI  - Quantification of differences in the effective atomic numbers of healthy and
      cancerous tissues: a discussion in the context of diagnostics and dosimetry.
AB  - PURPOSE: There are a range of genetic and nongenetic factors influencing the
      elemental composition of different human tissues. The elemental composition of
      cancerous tissues frequently differs from healthy tissue of the same organ,
      particularly in high-Z trace element concentrations. For this reason, one could
      suggest that this may be exploited in diagnostics and perhaps even influence
      dosimetry. METHODS: In this work, for the first time, effective atomic numbers
      are computed for common cancerous and healthy tissues using a robust, energy
      dependent approach between 10 keV and 100 MeV. These are then quantitatively
      compared within the context of diagnostics and dosimetry. RESULTS: Differences
      between effective atomic numbers of healthy and diseased tissues are found to be
      typically less than 10%. Fibrotic tissues and calcifications of the breast
      exhibit substantial (tens to hundreds of percent) differences to healthy tissue.
      Expectedly, differences are most pronounced in the photoelectric regime and
      consequently most relevant for kV imaging/therapy and radionuclides with
      prominent low-energy peaks. Cancerous tissue of the testes and stomach have lower
      effective atomic numbers than corresponding healthy tissues, while diseased
      tissues of the other organ sites typically have higher values. CONCLUSIONS: As
      dose calculation approaches improve in accuracy, there may be an argument for the
      explicit inclusion of pathologies. This is more the case for breast, penile,
      prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidney
      cancer. The calculated data suggest dual-energy computed tomography could
      potentially improve lesion identification in the aforementioned organs (with the
      exception of testicular cancer), with most import in breast imaging. Ultimately,
      however, the differences are very small. It is likely that the assumption of a
      generic "tissue ramp" in planning will be sufficient for the foreseeable future,
      and that the Z differences do not notably aid lesion detection beyond that
      already facilitated by differences in mass density.

PMID- 22957612
TI  - Human contrast-detail performance with declining contrast.
AB  - PURPOSE: How do display settings and ambient lighting affect contrast detection
      thresholds for human observers? Can recalibrating a display for high ambient
      lighting improve object detection? METHODS: Contrast/detail (CD) threshold
      detection performance was measured for observers using four color displays with
      varying overall contrast (e.g., differing maximum luminance and ambient lighting
      conditions). Detailed mapping of contrast detection performance (for fixed object
      size) was tracked as a function of: display maximum luminance, ambient lighting
      changes (with and without recalibrating for the higher ambience), and the
      performance of radiologists vs. nonradiologists. RESULTS: The initial phase was
      analyzed with a hierarchical linear model of observer performance using:
      background gray level, maximum display luminance, and radiologist vs.
      nonradiologist. The only statistically significant finding was a maximum
      luminance of 100 cd/m(2) display performing worse than a baseline peak of 400
      cd/m(2). The second phase examined ambient lighting effects on detection
      thresholds. Background gray level and maximum display luminance were examined
      coupled with ambient lighting for: baseline at 30, 435 uncorrected, and 435 lx
      with display recalibration for the ambient conditions. Results showed ambient
      correction improved sensitivity for small background digital driving level, but
      not at higher luminance backgrounds. CONCLUSIONS: For CD study, nonradiologist
      observers can be used without loss of applicability. Contrast detection
      thresholds improved significantly between displays with peak luminance from 100
      cd/m(2) to 200 cd/m(2), but improvement beyond that was not statistically
      significant for contrast detection thresholds in a reading room environment.
      Applying a calibration correction at high ambience (435 lx) improved detection
      tasks primarily in the darker background regions.

PMID- 22957613
TI  - The effect of different bleaching wavelengths on the sensitivity of Al(2)O(3):C
      optically stimulated luminescence detectors (OSLDs) exposed to 6 MV photon beams.
AB  - PURPOSE: To determine the effect of different bleaching wavelengths on the
      response of Al(2)O(3):C optically stimulated luminescence detectors (OSLDs)
      exposed to accumulated doses of 6 MV photon beams. METHODS: In this study the
      authors used nanoDot OSLDs readout with a MicroStar reader. The authors first
      characterized the dose-response, fading, and OSL signal loss of OSLDs exposed to
      doses from 0.5 to 10 Gy. To determine the effect of different bleaching
      wavelengths on the OSLDs' response, the authors optically treated the OSLDs with
      26 W fluorescent lamps in two modes: (i) directly under the lamps for 10, 120,
      and 600 min and (ii) with a long-pass filter for 55, 600, and 2000 min. Changes
      in the OSLDs' sensitivity were determined for an irradiation-readout-bleaching
      readout cycle after irradiations with 1 and 10 Gy dose fractions. RESULTS: The
      OSLDs presented supralinearity for doses of 2 Gy and above. The signal loss rates
      for sequential readouts were (0.287 +/- 0.007)% per readout in the reader's
      strong-stimulation mode, and (0.019 +/- 0.002)% and (0.035 +/- 0.007)% per
      readout for doses of 0.2 and 10 Gy, respectively, in the reader's weak
      stimulation mode. Fading half-life values ranged from (0.98 +/- 0.14) min to
      (1.77 +/- 0.24) min and fading showed dose dependence for the first 10-min
      interval. For 10 and 55 min bleaching using modes (i) and (ii), the OSL signal
      increased 14% for an accumulated dose of 7 Gy (1 Gy fractions). For OSLDs exposed
      to 10 Gy fractions, the OSL signal increased 30% and 25% for bleaching modes (i)
      and (ii) and accumulated dose of 70 Gy, respectively. For 120 and 600 min
      bleaching using modes (i) and (ii), the OSL signal increased 2.7% and 1.5% for an
      accumulated dose of 7 Gy (1 Gy fractions), respectively. For 10 Gy fractions, the
      signal increased 14% for bleaching mode (i) (120 min bleaching) and decreased
      1.3% for bleaching mode (ii) (600 min bleaching) for an accumulated dose of 70
      Gy. For 600 and 2000 min bleaching using modes (i) and (ii), the signal increased
      2.3% and 1.8% for an accumulated dose of 7 Gy (1 Gy fractions), respectively. For
      10 Gy fractions, the signal increased 10% for mode (i) (600 min bleaching) and
      decreased 2.5% for mode (ii) (2000 min bleaching) for an accumulated dose of 70
      Gy. CONCLUSIONS: The dose-response of nanoDot OSLDs read using the MicroStar
      reader presented supralinearity for doses of 2 Gy and above. The signal loss as a
      function of sequential readouts depended on dose. Fading also depended on dose
      for the first 10-min interval. For dose fractions of 1 and 10 Gy, OSLDs may be
      reused within 3% and 5% accuracies up to the maximum accumulated dose of 7 and 70
      Gy investigated in this study, respectively. These accuracies were obtained after
      the OSLDs were bleached with a light source with wavelengths above about 495 nm.
      The authors also concluded that changes in sensitivity of OSLDs depended on
      bleaching time, accumulated dose, and wavelength spectrum of the bleaching
      source.

PMID- 22957614
TI  - Calculation of strain images of a breast-mimicking phantom from 3D CT image data.
AB  - PURPOSE: Elastography is a medical imaging modality to visualize the elasticity
      of soft tissues. Ultrasound and MRI have been exclusively used for elastography
      of soft tissues since they can sensitize the tissues' minute displacements of an
      order of MUm. It is known that ultrasound and MRI elastography show cancerous
      tissues with much higher contrast than conventional ultrasound and MRI. To
      evaluate possibility of combining elastography with x-ray imaging, we have
      calculated strain images of a breast-mimicking phantom from its 3D CT image data.
      METHODS: We first simulated the x-ray elastography using a FEM model which
      incorporated both the elasticity and x-ray attenuation behaviors of breast
      tissues. After validating the x-ray elastography scheme by simulation, we made a
      breast-mimicking phantom that contained a hard inclusion against soft background.
      With a micro-CT, we took 3D images of the phantom twice, changing the compressing
      force to the phantom. From the two 3D phantom images taken with two different
      compression ratios, we calculated the displacement vector maps that represented
      the compression-induced pixel displacements. In calculating the displacement
      vectors, we tracked the movements of image feature patterns from the less
      compressed-phantom images to the more-compressed-phantom images using the 3D
      image correlation technique. We obtained strain images of the phantom by
      differentiating the displacement vector maps. RESULTS: The FEM simulation has
      shown that x-ray strain imaging is possible by tracking image feature patterns in
      the 3D CT images of the breast-mimicking phantom. The experimental displacement
      and strain images of a breast-mimicking phantom, obtained from the 3D micro-CT
      images taken with 0%-3% compression ratios, show behaviors similar to the FEM
      simulation results. The contrast and noise performance of the strain images
      improves as the phantom compression ratio increases. CONCLUSIONS: We have
      experimentally shown that we can improve x-ray strain image quality by applying
      3D image correlation to the two sets of 3D CT images taken with different
      compression ratios. But, we need further investigations to evaluate the strain
      imaging performance considering the noise and decorrelation effects as well as
      the extra dose caused by two scans.

PMID- 22957615
TI  - Investigation of four-dimensional (4D) Monte Carlo dose calculation in real-time
      tumor tracking stereotatic body radiotherapy for lung cancers.
AB  - PURPOSE: To investigate the dosimetric variations and radiobiological impacts as
      a consequence of delivering treatment plans of 3D nature in 4D manner based on
      the 4D Monte Carlo treatment planning framework implemented on Cyberknife.
      METHODS: Dose distributions were optimized on reference 3D images at end of
      exhale phase of a 4DCT dataset for 25 lung cancer patients treated with 60 Gy/3Fx
      or 48 Gy/4Fx. Deformable image registrations between individual 3DCT images to
      the reference 3DCT image in the 4DCT study were performed to interpolate doses
      calculated on multiple anatomical geometries back on to the reference geometry to
      compose a 4D dose distribution that included the tracking beam motion and organ
      deformation. The 3D and 4D dose distributions that were initially calculated with
      the equivalent path-length (EPL) algorithm (3D(EPL) dose and 4D(EPL) dose) were
      recalculated with the Monte Carlo algorithm (3D(MC) dose and 4D(MC) dose).
      Dosimetric variations of V(60Gy/48Gy) and D(99) of GTV, mean doses to the lung
      and the heart and maximum dose (D(1)) of the spinal cord as a consequence of
      tracking beam motion in deforming anatomy, dose calculation algorithm, and both
      were quantified by the relative change from 4D(MC) to 3D(MC) doses, from 4D(MC)
      to 4D(EPL) doses, and from 4D(MC) to 3D(EPL) doses, respectively. RESULTS:
      Comparing 4D(MC) to 3D(EPL) plans, V(60Gy / 48Gy) and D(99) of GTV decreased
      considerably by 13 +/- 22% (mean +/- 1SD) and 9.2 +/- 5.5 Gy but changes of
      normal tissue doses were not more than 0.5 Gy on average. The generalized
      equivalent uniform dose (gEUD) and tumor control probability (TCP) were reduced
      by 14.3 +/- 8.8 Gy and 7.5 +/- 5.2%, and normal tissue complication probability
      (NTCP) for myelopathy and pericarditis were close to zero and NTCP for radiation
      pneumonitis was reduced by 2.5% +/- 4.1%. Comparing 4D(MC) to 4D(EPL) plans found
      decreased V(60Gy/48Gy) and D(99) by 12.3% +/- 21.6% and 7.3 +/- 5.3 Gy, the
      normal tissues doses by 0.5 Gy on average, gEUD and TCP by 13.0 +/- 8.6 Gy and
      7.1% +/- 5.1%. Comparing 4D(MC) to 3D(MC) doses, V(60Gy/48Gy) and D(99) of GTV
      was reduced by 5.2% +/- 8.8% and 2.6 +/- 3.3 Gy, and normal tissues hardly
      changed from 4D(MC) to 3D(MC) doses. The corresponding decreases of gEUD and TCP
      were 2.8 +/- 4.0 Gy and 1.6 +/- 2.4%. CONCLUSIONS: The large discrepancy between
      original 3D(EPL) plan and benchmarking 4D(MC) plan is predominately due to dose
      calculation algorithms as the tracking beam motion and organ deformation hardly
      influenced doses of normal tissues and moderately decreased V(60Gy/48Gy) and
      D(99) of GTV. It is worth to make a thoughtful weight of the benefits of full
      4D(MC) dose calculation and consider 3D(MC) dose calculation as a compromise of
      4D(MC) dose calculation considering the multifold computation time.

PMID- 22957616
TI  - Experimental validation of an intrasubject elastic registration algorithm for
      dynamic-3D ultrasound images.
AB  - PURPOSE: In image-guided therapy, real-time visualization of the anatomy and
      adjustments in the therapy plan due to anatomical motions during the procedure is
      of outmost importance. 3D ultrasound has the potential to enable this real-time
      monitoring; however, nonrigid registration of a sequence of 3D ultrasound volumes
      remains to be a challenging problem. The authors present our recent results on
      the development of a computationally inexpensive feature-based registration
      algorithm for elastic alignment of dynamic-3D ultrasound images. METHODS: Our
      algorithm uses attribute vectors, based on the image intensity and gradient
      information, to perform feature-based matching in a sequence of 3D ultrasound
      images. Prior information from both the fixed and previous moving images is
      utilized to track features throughout the 3D image series. The algorithm has been
      compared to various publicly available registration techniques, i.e., the B
      splines deformable registration, the symmetric forces Demons, and the fast free
      form deformable registration method. RESULTS: Using a series of validation
      experiments on datasets collected from carotid artery, liver, and kidney of 20
      subjects, the authors demonstrate that the feature-based, B-splines, Demons, and
      fast free-form deformable registration techniques can all recover volume
      deformations in a 3D ultrasound image series with reasonable accuracy; however,
      the proposed feature-based registration technique has substantial computational
      advantage over the other approaches. CONCLUSIONS: The proposed feature-based
      registration technique has the potential for real-time implementation on a
      computationally inexpensive platform and has the capability of recovering
      nonrigid deformations in tissue with reasonable accuracy.

PMID- 22957617
TI  - Statistical CT noise reduction with multiscale decomposition and penalized
      weighted least squares in the projection domain.
AB  - PURPOSES: The suppression of noise in x-ray computed tomography (CT) imaging is
      of clinical relevance for diagnostic image quality and the potential for
      radiation dose saving. Toward this purpose, statistical noise reduction methods
      in either the image or projection domain have been proposed, which employ a
      multiscale decomposition to enhance the performance of noise suppression while
      maintaining image sharpness. Recognizing the advantages of noise suppression in
      the projection domain, the authors propose a projection domain multiscale
      penalized weighted least squares (PWLS) method, in which the angular sampling
      rate is explicitly taken into consideration to account for the possible variation
      of interview sampling rate in advanced clinical or preclinical applications.
      METHODS: The projection domain multiscale PWLS method is derived by converting an
      isotropic diffusion partial differential equation in the image domain into the
      projection domain, wherein a multiscale decomposition is carried out. With
      adoption of the Markov random field or soft thresholding objective function, the
      projection domain multiscale PWLS method deals with noise at each scale. To
      compensate for the degradation in image sharpness caused by the projection domain
      multiscale PWLS method, an edge enhancement is carried out following the noise
      reduction. The performance of the proposed method is experimentally evaluated and
      verified using the projection data simulated by computer and acquired by a CT
      scanner. RESULTS: The preliminary results show that the proposed projection
      domain multiscale PWLS method outperforms the projection domain single-scale PWLS
      method and the image domain multiscale anisotropic diffusion method in noise
      reduction. In addition, the proposed method can preserve image sharpness very
      well while the occurrence of "salt-and-pepper" noise and mosaic artifacts can be
      avoided. CONCLUSIONS: Since the interview sampling rate is taken into account in
      the projection domain multiscale decomposition, the proposed method is
      anticipated to be useful in advanced clinical and preclinical applications where
      the interview sampling rate varies.

PMID- 22957618
TI  - Determination of the beam quality index of high-energy photon beams under
      nonstandard reference conditions.
AB  - PURPOSE: At some modern radiotherapy machines it is not possible to achieve
      reference conditions for the measurement of beam quality indices used in
      dosimetry codes of practice, such as IAEA TRS-398 and AAPM TG-51. This work aims
      at providing self-consistent and simpler expressions and more accurate fits for a
      limited range of beams of interest than have been proposed previously for
      deriving these beam quality indices from measurements. METHODS: The starting
      point is a formula proposed by Sauer [Med. Phys. 36, 4168-4172 (2009)] for
      deriving the beam quality index used in IAEA TRS-398, TPR(20,10), from a
      measurement of the tissue phantom ratio at depths of 20 cm and 10 cm in water for
      an s * s cm(2) (equivalent) square field, TPR(20,10)(s). First, a self-consistent
      version of this formula is established followed by a simpler version by making a
      linear approximation. A similar approach is proposed to derive the beam quality
      index used in AAPM TG-51, %dd(10)(X), from a measurement of PDD(10)(s), the
      percentage depth dose at 10 cm for a square field with size s. All models were
      fitted to subsets of relevant data from BJR supplement 25. RESULTS: The linear
      models for TPR(20,10)(s) and exponential models for PDD(10)(s) as a function of
      the (equivalent) square field size can reproduce the beam quality within 0.3% and
      beam quality correction factors within 0.05% for square field sizes ranging from
      4 cm to 12 cm and nominal photon energies from 4 MV to 12 MV. For higher energy
      beams the errors are only slightly worse but for %dd(10)(X), an additional
      uncertainty component has to be considered for the electron contamination
      correction. CONCLUSIONS: The models proposed here can be used in practical
      recommendations for the dosimetry of small and nonstandard fields.

PMID- 22957619
TI  - Characterization of adaptive statistical iterative reconstruction algorithm for
      dose reduction in CT: A pediatric oncology perspective.
AB  - PURPOSE: This study demonstrates a means of implementing an adaptive statistical
      iterative reconstruction (ASiRTM) technique for dose reduction in computed
      tomography (CT) while maintaining similar noise levels in the reconstructed
      image. The effects of image quality and noise texture were assessed at all
      implementation levels of ASiRTM. Empirically derived dose reduction limits were
      established for ASiRTM for imaging of the trunk for a pediatric oncology
      population ranging from 1 yr old through adolescence/adulthood. METHODS: Image
      quality was assessed using metrics established by the American College of
      Radiology (ACR) CT accreditation program. Each image quality metric was tested
      using the ACR CT phantom with 0%-100% ASiRTM blended with filtered back
      projection (FBP) reconstructed images. Additionally, the noise power spectrum
      (NPS) was calculated for three common reconstruction filters of the trunk. The
      empirically derived limitations on ASiRTM implementation for dose reduction were
      assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms.
      To assess dose reduction limits, the phantoms were scanned in increments of
      increased noise index (decrementing mA using automatic tube current modulation)
      balanced with ASiRTM reconstruction to maintain noise equivalence of the 0%
      ASiRTM image. RESULTS: The ASiRTM algorithm did not produce any unfavorable
      effects on image quality as assessed by ACR criteria. Conversely, low-contrast
      resolution was found to improve due to the reduction of noise in the
      reconstructed images. NPS calculations demonstrated that images with lower
      frequency noise had lower noise variance and coarser graininess at progressively
      higher percentages of ASiRTM reconstruction; and in spite of the similar
      magnitudes of noise, the image reconstructed with 50% or more ASiRTM presented a
      more smoothed appearance than the pre-ASiRTM 100% FBP image. Finally, relative to
      non-ASiRTM images with 100% of standard dose across the pediatric phantom age
      spectrum, similar noise levels were obtained in the images at a dose reduction of
      48% with 40% ASIRTM and a dose reduction of 82% with 100% ASIRTM. CONCLUSIONS:
      The authors' work was conducted to identify the dose reduction limits of ASiRTM
      for a pediatric oncology population using automatic tube current modulation.
      Improvements in noise levels from ASiRTM reconstruction were adapted to provide
      lower radiation exposure (i.e., lower mA) instead of improved image quality. We
      have demonstrated for the image quality standards required at our institution, a
      maximum dose reduction of 82% can be achieved using 100% ASiRTM; however, to
      negate changes in the appearance of reconstructed images using ASiRTM with a
      medium to low frequency noise preserving reconstruction filter (i.e., standard),
      40% ASiRTM was implemented in our clinic for 42%-48% dose reduction at all
      pediatric ages without a visually perceptible change in image quality or image
      noise.

PMID- 22957620
TI  - Superiorization: an optimization heuristic for medical physics.
AB  - PURPOSE: To describe and mathematically validate the superiorization methodology,
      which is a recently developed heuristic approach to optimization, and to discuss
      its applicability to medical physics problem formulations that specify the
      desired solution (of physically given or otherwise obtained constraints) by an
      optimization criterion. METHODS: The superiorization methodology is presented as
      a heuristic solver for a large class of constrained optimization problems. The
      constraints come from the desire to produce a solution that is constraints
      compatible, in the sense of meeting requirements provided by physically or
      otherwise obtained constraints. The underlying idea is that many iterative
      algorithms for finding such a solution are perturbation resilient in the sense
      that, even if certain kinds of changes are made at the end of each iterative
      step, the algorithm still produces a constraints-compatible solution. This
      property is exploited by using permitted changes to steer the algorithm to a
      solution that is not only constraints-compatible, but is also desirable according
      to a specified optimization criterion. The approach is very general, it is
      applicable to many iterative procedures and optimization criteria used in medical
      physics. RESULTS: The main practical contribution is a procedure for
      automatically producing from any given iterative algorithm its superiorized
      version, which will supply solutions that are superior according to a given
      optimization criterion. It is shown that if the original iterative algorithm
      satisfies certain mathematical conditions, then the output of its superiorized
      version is guaranteed to be as constraints-compatible as the output of the
      original algorithm, but it is superior to the latter according to the
      optimization criterion. This intuitive description is made precise in the paper
      and the stated claims are rigorously proved. Superiorization is illustrated on
      simulated computerized tomography data of a head cross section and, in spite of
      its generality, superiorization is shown to be competitive to an optimization
      algorithm that is specifically designed to minimize total variation. CONCLUSIONS:
      The range of applicability of superiorization to constrained optimization
      problems is very large. Its major utility is in the automatic nature of producing
      a superiorization algorithm from an algorithm aimed at only constraints
      compatibility; while nonheuristic (exact) approaches need to be redesigned for a
      new optimization criterion. Thus superiorization provides a quick route to
      algorithms for the practical solution of constrained optimization problems.

PMID- 22957621
TI  - Influence of imaging source and panel position uncertainties on the accuracy of
      2D/3D image registration of cranial images.
AB  - PURPOSE: To determine the effects of imager source and panel positioning
      uncertainties on the accuracy of dual intensity-based 2D/3D image registration of
      cranial images. METHODS: An open source 2D/3D image registration algorithm has
      been developed for registration of two orthogonal x-rays to a 3D volumetric
      image. The initialization files of the algorithm allow for nine degrees of
      freedom system calibration including x, y, z positions of the source and panel,
      and three rotational degrees of freedom of the panel about each of the three
      translational axes. A baseline system calibration was established and a baseline
      2D/3D registration between two orthogonal x-rays and the volumetric image was
      determined. The calibration file was manipulated to insert errors into each of
      the nine calibration variables of both imager geometries. Rigid six degrees of
      freedom registrations were iterated for each panel or source positional error
      over a range of predetermined calibration errors to determine the resulting error
      in the registration versus the baseline registration due to the manipulated error
      of the panel or source calibration. RESULTS: Panel and source translational
      errors orthogonal to the imager/panel axis introduced the greatest errors in the
      registration accuracy (4.0 mm geometric error results in up to 2.7 mm
      registration error). Panel rotation about the imaging direction also resulted in
      errors of the registration (2.0 degrees  geometric error results in up to 1.7
      degrees  registration error). Differences in magnification and panel tilt and
      roll, i.e., source and/or panel translation along the imaging direction and panel
      rotations about the orthogonal axes had minimal effects on the registration
      accuracy (below 0.3 mm and 0.2 degrees  registration error). CONCLUSIONS: While
      five of the nine imaging system variables were found to have a considerable
      effect on 2D/3D registration accuracy of cranial images, the other four variables
      showed minimal effects. Vendors typically provide simplified calibration
      procedures which aim to remove encountered geometric uncertainties by accounting
      for two panel translations. This study shows that at least the five relevant
      positional variables should be separately calibrated, if accurate alignment is
      required for 2D/3D registration.

PMID- 22957623
TI  - Magnetostatic focal spot correction for x-ray tubes operating in strong magnetic
      fields using iterative optimization.
AB  - PURPOSE: Combining x-ray fluoroscopy and MR imaging systems for guidance of
      interventional procedures has become more commonplace. By designing an x-ray tube
      that is immune to the magnetic fields outside of the MR bore, the two systems can
      be placed in close proximity to each other. A major obstacle to robust x-ray tube
      design is correcting for the effects of the magnetic fields on the x-ray tube
      focal spot. A potential solution is to design active shielding that locally
      cancels the magnetic fields near the focal spot. METHODS: An iterative
      optimization algorithm is implemented to design resistive active shielding coils
      that will be placed outside the x-ray tube insert. The optimization procedure
      attempts to minimize the power consumption of the shielding coils while
      satisfying magnetic field homogeneity constraints. The algorithm is composed of a
      linear programming step and a nonlinear programming step that are interleaved
      with each other. The coil results are verified using a finite element space
      charge simulation of the electron beam inside the x-ray tube. To alleviate
      heating concerns an optimized coil solution is derived that includes a neodymium
      permanent magnet. Any demagnetization of the permanent magnet is calculated prior
      to solving for the optimized coils. The temperature dynamics of the coil
      solutions are calculated using a lumped parameter model, which is used to
      estimate operation times of the coils before temperature failure. RESULTS: For a
      magnetic field strength of 88 mT, the algorithm solves for coils that consume 588
      A/cm(2). This specific coil geometry can operate for 15 min continuously before
      reaching temperature failure. By including a neodymium magnet in the design the
      current density drops to 337 A/cm(2), which increases the operation time to 59
      min. Space charge simulations verify that the coil designs are effective, but for
      oblique x-ray tube geometries there is still distortion of the focal spot shape
      along with deflections of approximately 3 mm in the radial and circumferential
      directions on the anode. CONCLUSIONS: Active shielding is an attractive solution
      for correcting the effects of magnetic fields on the x-ray focal spot. If
      extremely long fluoroscopic exposure times are required, longer operation times
      can be achieved by including a permanent magnet with the active shielding design.

PMID- 22957622
TI  - Four-dimensional dose distributions of step-and-shoot IMRT delivered with real
      time tumor tracking for patients with irregular breathing: constant dose rate vs
      dose rate regulation.
AB  - PURPOSE: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that
      programs the MLC to track the tumor under regular breathing and adapts to
      breathing irregularities during delivery using dose rate regulation. Constant
      dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to
      account for intrafractional 3D target motion according to real-time information
      of target location obtained from an independent position monitoring system. The
      purpose of this study is to illustrate the differences in the effectiveness and
      delivery accuracy between these two tracking methods in the presence of breathing
      irregularities. METHODS: Step-and-shoot IMRT plans optimized at a reference phase
      were extended to remaining phases to generate 10-phased 4D-IMRT plans using
      segment aperture morphing (SAM) algorithm, where both tumor displacement and
      deformation were considered. A SAM-based 4D plan has been demonstrated to provide
      better plan quality than plans not considering target deformation. However,
      delivering such a plan requires preprogramming of the MLC aperture sequence.
      Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated
      assuming the breathing period is either shorter or longer than the planning day,
      for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid
      motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed
      up or slow down delivery as needed such that each planned segment is delivered at
      the planned breathing phase. In CDRT, MLC is separately controlled to follow the
      tumor motion, but dose rate was kept constant. In addition to breathing period
      change, effect of breathing amplitude variation on target and critical tissue
      dose distribution is also evaluated. RESULTS: Delivery of preprogrammed 4D plans
      by the CDRT method resulted in an average of 5% increase in target dose and
      noticeable increase in organs at risk (OAR) dose when patient breathing is either
      10% faster or slower than the planning day. In contrast, DRRT method showed less
      than 1% reduction in target dose and no noticeable change in OAR dose under the
      same breathing period irregularities. When +/-20% variation of target motion
      amplitude was present as breathing irregularity, the two delivery methods show
      compatible plan quality if the dose distribution of CDRT delivery is
      renormalized. CONCLUSIONS: Delivery of 4D-IMRT treatment plans, stemmed from 3D
      step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two
      dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate
      regulation. Comparison of cumulative dose distribution indicates that the
      preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT
      strategy, as it compensates the interplay between patient breathing irregularity
      and tracking delivery without compromising the segment-weight modulation.

PMID- 22957624
TI  - Biological effect of dose distortion by fiducial markers in spot-scanning proton
      therapy with a limited number of fields: a simulation study.
AB  - PURPOSE: In accurate proton spot-scanning therapy, continuous target tracking by
      fluoroscopic x ray during irradiation is beneficial not only for respiratory
      moving tumors of lung and liver but also for relatively stationary tumors of
      prostate. Implanted gold markers have been used with great effect for positioning
      the target volume by a fluoroscopy, especially for the cases of liver and
      prostate with the targets surrounded by water-equivalent tissues. However, recent
      studies have revealed that gold markers can cause a significant underdose in
      proton therapy. This paper focuses on prostate cancer and explores the
      possibility that multiple-field irradiation improves the underdose effect by
      markers on tumor-control probability (TCP). METHODS: A Monte Carlo simulation was
      performed to evaluate the dose distortion effect. A spherical gold marker was
      placed at several characteristic points in a water phantom. The markers were with
      two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam
      arrangements of single-field uniform dose (SFUD) were examined: one lateral
      field, two opposite lateral fields, and three fields (two opposite lateral fields
      + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and
      a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in
      37 fractions. The ratios of TCP to that without the marker (TCP(r)) were compared
      with the parameters of the marker sizes, number of fields, and marker positions.
      To take into account the dependence of biological parameters in TCP model,
      alpha/beta values of 1.5, 3, and 10 Gy (RBE) were considered. RESULTS: It was
      found that the marker of 1.5 mm diameter does not affect the TCPs with all
      alpha/beta values when two or more fields are used. On the other hand, if the
      marker diameter is 2 mm, more than two irradiation fields are required to
      suppress the decrease in TCP from TCP(r) by less than 3%. This is especially true
      when multiple (two or three) markers are used for alignment of a patient.
      CONCLUSIONS: It is recommended that 1.5-mm markers be used to avoid the reduction
      of TCP as well as to spare the surrounding critical organs, as long as the
      markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more
      than two fields should be used and the markers should not be placed close to the
      distal edge of any of the beams.

PMID- 22957625
TI  - Four-dimensional cone beam CT reconstruction and enhancement using a temporal
      nonlocal means method.
AB  - PURPOSE: Four-dimensional cone beam computed tomography (4D-CBCT) has been
      developed to provide respiratory phase-resolved volumetric imaging in image
      guided radiation therapy. Conventionally, it is reconstructed by first sorting
      the x-ray projections into multiple respiratory phase bins according to a
      breathing signal extracted either from the projection images or some external
      surrogates, and then reconstructing a 3D CBCT image in each phase bin
      independently using FDK algorithm. This method requires adequate number of
      projections for each phase, which can be achieved using a low gantry rotation or
      multiple gantry rotations. Inadequate number of projections in each phase bin
      results in low quality 4D-CBCT images with obvious streaking artifacts. 4D-CBCT
      images at different breathing phases share a lot of redundant information,
      because they represent the same anatomy captured at slightly different temporal
      points. Taking this redundancy along the temporal dimension into account can in
      principle facilitate the reconstruction in the situation of inadequate number of
      projection images. In this work, the authors propose two novel 4D-CBCT
      algorithms: an iterative reconstruction algorithm and an enhancement algorithm,
      utilizing a temporal nonlocal means (TNLM) method. METHODS: The authors define a
      TNLM energy term for a given set of 4D-CBCT images. Minimization of this term
      favors those 4D-CBCT images such that any anatomical features at one spatial
      point at one phase can be found in a nearby spatial point at neighboring phases.
      4D-CBCT reconstruction is achieved by minimizing a total energy containing a data
      fidelity term and the TNLM energy term. As for the image enhancement, 4D-CBCT
      images generated by the FDK algorithm are enhanced by minimizing the TNLM
      function while keeping the enhanced images close to the FDK results. A forward
      backward splitting algorithm and a Gauss-Jacobi iteration method are employed to
      solve the problems. The algorithms implementation on GPU is designed to avoid
      redundant and uncoalesced memory access, in order to ensure a high computational
      efficiency. Our algorithms have been tested on a digital NURBS-based cardiac
      torso phantom and a clinical patient case. RESULTS: The reconstruction algorithm
      and the enhancement algorithm generate visually similar 4D-CBCT images, both
      better than the FDK results. Quantitative evaluations indicate that, compared
      with the FDK results, our reconstruction method improves contrast-to-noise-ratio
      (CNR) by a factor of 2.56-3.13 and our enhancement method increases the CNR by
      2.75-3.33 times. The enhancement method also removes over 80% of the streak
      artifacts from the FDK results. The total computation time is 509-683 s for the
      reconstruction algorithm and 524-540 s for the enhancement algorithm on an NVIDIA
      Tesla C1060 GPU card. CONCLUSIONS: By innovatively taking the temporal redundancy
      among 4D-CBCT images into consideration, the proposed algorithms can produce high
      quality 4D-CBCT images with much less streak artifacts than the FDK results, in
      the situation of inadequate number of projections.

PMID- 22957626
TI  - Radiation therapy effects on white matter fiber tracts of the limbic circuit.
AB  - PURPOSE: To segment fiber tracts in the limbic circuit and to assess their
      sensitivity to radiation therapy (RT). METHODS: Twelve patients with brain
      metastases who had received fractionated whole brain radiation therapy to 30 Gy
      or 37.5 Gy were included in the study. Diffusion weighted images were acquired
      pre-RT, at the end of RT, and 1-month post-RT. The fornix, corpus callosum, and
      cingulum were extracted from diffusion weighted images by combining fiber
      tracking and segmentation methods based upon characteristics of the fiber
      bundles. Cingulum was segmented by a seed-based tractography, fornix by a region
      of interests (ROI)-based tractography, and corpus callosum by a level-set
      segmentation algorithm. The radiation-induced longitudinal changes of diffusion
      indices of the structures were evaluated. RESULTS: Significant decreases were
      observed in the fractional anisotropy of the posterior part of the cingulum,
      fornix, and corpus callosum from pre-RT to end of RT by -14.0%, -12.5%, and 
      5.2%, respectively (p < 0.001), and from pre-RT to 1-month post-RT by -11.9%, 
      12.8%, and -6.4%, respectively (p < 0.001). Moreover, significant increases were
      observed in the mean diffusivity of the corpus callosum and the posterior part of
      the cingulum from pre-RT to end of RT by 6.8% and 6.5%, respectively, and from
      pre-RT to 1-month post-RT by 8.5% and 6.3%, respectively. The increase in the
      radial diffusivity primarily contributed to the significant decrease in the
      fractional anisotropy, indicating that demyelination is the predominant radiation
      effect on the white matter structures. CONCLUSIONS: Our findings indicate that
      the fornix and the posterior part of the cingulum are significantly susceptible
      to radiation damage. We have developed robust computer-aided semiautomatic
      segmentation and fiber tracking tools to facilitate the ROI delineation of
      critical structures, which is important for assessment of radiation damage in a
      longitudinal fashion.

PMID- 22957627
TI  - Validation of a postinjection transmission method for actual rat brain PET.
AB  - PURPOSE: Postinjection transmission positron emission tomography (PET) may be
      useful for shortening the total scan time. In this study, the effect of post
      transmission scanning was assessed using PET on a phantom (NU4) and actual rat
      brain. METHODS: Transmission was performed using (57)Co for 15 min. After a 15
      min pre-transmission scan, emission PET was performed in list mode for 1 h,
      followed by an additional 15-min post-transmission scan. To compare the pre
      transmission and post-transmission results, we measured nonuniformity, the
      recovery coefficient, and the spillover ratio (SOR) using NU4 and rat phantoms.
      The authors also assessed cerebral glucose metabolism using (18)F
      fluorodeoxyglucose (FDG) PET and the binding potential for (18)F-fluorinated N-3
      fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl)nortropane (FP-CIT) in
      rat brain for differences between pre-transmission and post-transmission
      scanning. RESULTS: Nonuniformity and the SORs for air and water were comparable
      on the pre-transmission and post-transmission scans. With FDG-PET, after
      attenuation and scatter corrections no differences were observed in the brain
      regions on the pre-transmission and post-transmission scans. With FP-CIT-PET, the
      binding potentials were also not significantly different. CONCLUSIONS: In the
      present study, we validated a post-transmission method for PET of the rat brain.
      Post-transmission PET was reliable, and the results were comparable to those of
      pre-transmission PET. Post-transmission PET eliminates the early tracer uptake
      time in the PET imaging, making it possible to determine uptake in the conscious
      subject, which may provide more realistic, "normal" metabolic measurements. Thus,
      post-transmission PET may be a useful option for increasing the number of
      subjects who can be evaluated.

PMID- 22957628
TI  - Image quality evaluation of breast tomosynthesis with synchrotron radiation.
AB  - PURPOSE: This study investigates the image quality of tomosynthesis slices
      obtained from several acquisition sets with synchrotron radiation using a breast
      phantom incorporating details that mimic various breast lesions, in a
      heterogeneous background. METHODS: A complex Breast phantom (MAMMAX) with a
      heterogeneous background and thickness that corresponds to 4.5 cm compressed
      breast with an average composition of 50% adipose and 50% glandular tissue was
      assembled using two commercial phantoms. Projection images using acquisition arcs
      of 24 degrees , 32 degrees , 40 degrees , 48 degrees , and 56 degrees  at
      incident energy of 17 keV were obtained from the phantom with the synchrotron
      radiation for medical physics beamline at ELETTRA Synchrotron Light Laboratory.
      The total mean glandular dose was set equal to 2.5 mGy. Tomograms were
      reconstructed with simple multiple projection algorithm (MPA) and filtered MPA.
      In the latter case, a median filter, a sinc filter, and a combination of those
      two filters were applied on the experimental data prior to MPA reconstruction.
      Visual inspection, contrast to noise ratio, contrast, and artifact spread
      function were the figures of merit used in the evaluation of the visualisation
      and detection of low- and high-contrast breast features, as a function of the
      reconstruction algorithm and acquisition arc. To study the benefits of using
      monochromatic beams, single projection images at incident energies ranging from
      14 to 27 keV were acquired with the same phantom and weighted to synthesize
      polychromatic images at a typical incident x-ray spectrum with W target. RESULTS:
      Filters were optimised to reconstruct features with different attenuation
      characteristics and dimensions. In the case of 6 mm low-contrast details,
      improved visual appearance as well as higher contrast to noise ratio and contrast
      values were observed for the two filtered MPA algorithms that exploit the sinc
      filter. These features are better visualized at extended arc length, as the
      acquisition arc of 56 degrees  with 15 projection images demonstrates the highest
      image reconstruction quality. For microcalcifications, filtered MPA implemented
      with a combination of median and sinc filters indicates better feature appearance
      due to efficient suppression of background tissue. The image quality of these
      features is less sensitive to the acquisition arc. Calcifications with size
      ranging from 170 to 500 MUm, like the ones presently studied, are well identified
      and visualized for all arcs used. The comparison of single projection images
      obtained under different beam conditions showed that the use of monochromatic
      beam can produce an image with higher contrast and contrast to noise ratio
      compared to an image corresponding to a polychromatic beam even when the latter
      is acquired with double incident exposure. CONCLUSIONS: Filter optimization in
      respect to the type of feature characteristics is important before the
      reconstruction. The MPA combined with median and sinc filters results in improved
      reconstruction of microcalcifications and low-contrast features. The latter are
      better visualized at extended arc length, while microcalcifications are less
      sensitive to this acquisition parameter. Use of monochromatic beams may result in
      tomographic images with higher contrast acquired at lower incident exposures.

PMID- 22957629
TI  - Technical note: improved implementation of Doppler broadening in MCNP5.
AB  - PURPOSE: Incoherent scattering has a substantial effect on spectroscopic
      measurements and simulations. Many general-purpose Monte Carlo codes include
      models that account for the effects of bound electrons on incoherent scattering,
      including Doppler broadening (DB). This work investigates the DB model used in
      the Monte Carlo N-particle transport code (MCNP5). METHODS: Simulations were run
      with three versions of MCNP5: v1.51, v1.60, and a modified form of v1.60
      (v1.60m). All simulations used the MCPLIB04 photon data library, which presents
      the electron subshell data for incoherent scattering in the form of a probability
      density function. In v1.60m, the source code was altered to sample the electron
      subshell from a cumulative density function instead. Each version of the code was
      tested using an identical set of simulations that investigated DB in a slab of
      silicon at scattering angles of 15 degrees , 30 degrees , and 45 degrees . For
      each angle, simulations were run for multiple energies between 200 keV and 800
      keV. The spectrum of singly-scattered photons at the exit of the slab was scored.
      Spectra were analytically calculated for comparison. RESULTS: In v1.51, DB was
      modeled for incident photon energies below 760 keV, 384 keV, and 260 keV at
      scattering angles of 15 degrees , 30 degrees , and 45 degrees , respectively.
      Above these energy thresholds, v1.51 did not model DB. The spectra calculated
      using v1.60 and v1.60m exhibited DB for all energy-angle combinations; however,
      v1.60m, exhibited more energy broadening than did v1.60. The spectra calculated
      with v1.60m agreed with the analytical calculations. CONCLUSIONS: MCNP5 v1.51 and
      v1.60 model partial broadening when used with the MCPLIB04 data library. MCNP5
      v1.60m models DB more accurately due to the form of the electron subshell data.
      In response to these results, Los Alamos National Laboratory has released a new
      photon data library, MCPLIB84, that presents the electron subshell data in
      cumulative distribution form. MCNP5 v1.60 should be used with this library when
      incoherent scattering has a significant impact on simulation results.

PMID- 22957630
TI  - Impact of flat panel-imager veiling glare on scatter-estimation accuracy and
      image quality of a commercial on-board cone-beam CT imaging system.
AB  - PURPOSE: The purposes of this study is to measure the low frequency drop (LFD) of
      the modulation transfer function (MTF), associated with the long tails of the
      detector point spread function (PSF) of an on-board flat panel imager and study
      its impact on cone-beam CT (CBCT) image quality and scatter measurement accuracy.
      METHODS: Two different experimental methods were used to characterize LFD and its
      associated PSF of a Varian OBI flat-panel detector system: the edge response
      function (ERF) method and the disk transfer function (DTF) method. PSF was
      estimated by fitting parametric models to these measurements for four values of
      the applied voltage (kVp). The resultant PSF was used to demonstrate the effect
      of LFD on image contrast and CT number accuracy in CBCT images reconstructed from
      synthetic datasets, as well as, accuracy of scatter measurements with the beam
      stop method. RESULTS: The MTFs derived from the measured ERF data revealed LFDs
      varying from 8% (at 60 kVp) to 10.5% (at 120 kVp), while the intensity of the
      long PSF tails was found to increase with increasing kVp. The veiling glare line
      spread functions derived from the ERF and DTF methods were in excellent
      agreement. Uncorrected veiling glare reduced contrast and the image intensity in
      CBCT reconstruction, near the phantom periphery (by 67 Hounsfield units in a 20
      cm-in-diameter water phantom) and (to a smaller degree) near inhomogeneities. Use
      of the bow-tie filter mitigated these effects. Veiling glare also resulted in
      about 10%-15% overestimation of the scatter-to-primary ratio when measured with
      the beam-stop or beam-stop array method. CONCLUSIONS: The long tails of the
      detector PSF were found to have a modest dependence of beam spectrum, which is
      reflected on the MTF curve LFD. Our findings show that uncorrected veiling glare
      can affect quantitative accuracy and contrast in CBCT imaging, based on flat
      panel imager. In addition, it results in overestimation of the scatter-to-primary
      ratio, measured with the beam-stop methods.

PMID- 22957631
TI  - Comparison of signal to noise ratios from spatial and frequency domain
      formulations of nonprewhitening model observers in digital mammography.
AB  - PURPOSE: Image quality indices based upon model observers are promising
      alternatives to laborious human readings of contrast-detail images. This is
      especially appealing in digital mammography as limiting values for contrast
      thresholds determine, according to some international protocols, the
      acceptability of these systems in the radiological practice. The objective of the
      present study was to compare the signal to noise ratios (SNR) obtained with two
      nonprewhitening matched filter model observer approaches, one in the spatial
      domain and the other in the frequency domain, and with both of them worked out
      for disks as present in the CDMAM phantom. METHODS: The analysis was performed
      using images acquired with the Siemens Novation and Inspiration digital
      mammography systems. The spatial domain formulation uses a series of high dose
      CDMAM images as the signal and a routine exposure of two flood images to
      calculate the covariance matrix. The frequency domain approach uses the
      mathematical description of a disk and modulation transfer function (MTF) and
      noise power spectrum (NPS) calculated from images. RESULTS: For both systems most
      of the SNR values calculated in the frequency domain were in very good agreement
      with the SNR values calculated in the spatial domain. Both the formulations in
      the frequency domain and in the spatial domain show a linear relationship between
      SNR and the diameter of the CDMAM discs. CONCLUSIONS: The results suggest that
      both formulations of the model observer lead to very similar figures of merit.
      This is a step forward in the adoption of figures of merit based on NPS and MTF
      for the acceptance testing of mammography systems.

PMID- 22957632
TI  - Discrimination of gastric cancer from normal by serum RNA based on surface
      enhanced Raman spectroscopy (SERS) and multivariate analysis.
AB  - PURPOSE: Here, the authors explore the feasibility of discriminating cancer
      patients from healthy controls by serum RNA detection based on surface-enhanced
      Raman spectroscopy (SERS) and multivariate analysis. METHODS: MgSO(4)-aggregated
      silver nanoparticles (Ag NP) as the SERS-active substrate presented strong SERS
      signals to RNA. SERS measurements were performed on two groups of serum RNA
      samples: one group from patients (n = 31) with gastric cancer and the other group
      from healthy volunteers (n = 34). RESULTS: Tentative assignments of the Raman
      bands in the normalized SERS spectra demonstrated that there are differential
      expressions of circulating RNA between the gastric cancer group and the control
      group. Principal component analysis (PCA) combined with linear discriminate
      analysis (LDA) was introduced to differentiate gastric cancer from normal and
      achieved sensitivity of 100% and specificity of 94.1%. CONCLUSIONS: This
      exploratory study demonstrated potential for developing serum RNA SERS analysis
      into a useful clinical tool for noninvasive screening and detection of cancer.

PMID- 22957633
TI  - A novel segmentation method for breast ultrasound images based on neutrosophic l
      means clustering.
AB  - PURPOSE: Fully automatic and accurate breast lesion segmentation is an essential
      and challenging task. In this paper, the authors develop a novel, effective, and
      fully automatic method for breast ultrasound (BUS) image segmentation. METHODS:
      The segmentation method utilizes a novel phase feature to improve the image
      quality, and a novel neutrosophic clustering approach to detect the accurate
      lesion boundary. First, a region of interest is generated to cut off complex
      background. After speckle reduction, an enhancement algorithm based on phase in
      max-energy orientation (PMO) is developed to further improve the image quality.
      The PMO is a newly proposed 2D phase feature obtained by filtering the image in
      the frequency domain and calculating the phase accumulation in the orientation
      with maximum energy. Finally, the authors propose a novel clustering approach
      called neutrosophic l-means (NLM) to detect the lesion boundary. NLM is a
      generalized clustering method that can be used to solve other clustering problems
      as well. In this paper, NLM is used to segment images with vague boundaries, and
      to deal with uncertainty better. To evaluate the performance of the proposed
      method, the authors compare it with the traditional fuzzy c-means clustering,
      active contour, level set, and watershed-based segmentation methods, using a
      common database. Radiologist's manual delineations are used as the golden
      standards. Five assessment metrics are utilized to evaluate the performance from
      different aspects. Both accuracy and efficiency are analyzed. Sensitivity
      analysis is also conducted to test the robustness of the proposed method.
      RESULTS: Compared with the other methods, the proposed method generates the most
      similar boundaries to the radiologist's manual delineations (TP rate is 92.4%, FP
      rate is 7.2%, and similarity rate is 86.3%; Hausdorff distance is 22.5 pixels and
      mean absolute distance is 4.8 pixels), with efficient processing speed (averagely
      9.8 s per image). Sensitivity analysis shows the robustness of the proposed
      method as well. CONCLUSIONS: The proposed method is a fully automatic
      segmentation method for BUS images that can generate accurate lesion boundaries
      even for complicated cases. The fast processing speed, robustness, and accuracy
      of the proposed method suggest its potential applications in clinics.

PMID- 22957634
TI  - Target-specific optimization of four-dimensional cone beam computed tomography.
AB  - PURPOSE: Under-sampling artifacts are a major problem in four-dimensional cone
      beam computed tomography (4D-CBCT) and may compromise evaluation of target
      motion. Several studies have addressed scan parameter selection for minimizing
      under-sampling artifacts; however, the role of the target characteristics in scan
      parameter selection has not been investigated. In this work, the authors
      evaluated 4D-CBCT performance by assessing the accuracy of target motion
      measurements for various target sizes and motions. The results may serve as
      patient-specific guidelines for scan parameters selection in 4D-CBCT. METHODS:
      The authors acquired 4D-CBCT scans of a moving phantom consisting of six water
      filled sphere targets of sizes 10-37 mm, using various scan times ranging from 30
      s to 3 min., setting the motion to 3-s and 6-s periods. The authors used
      automatic image registration to extract the target motion trajectories and
      evaluated these measurements for various target sizes and motions over various
      combinations of scan parameters including scan time, detector configuration,
      number of respiration phases, and reconstruction filters. RESULTS: The most
      important object parameter to 4D-CBCT performance was the period of motion.
      Measurements for the 6-s motion were always systematically less accurate than
      measurements for the 3-s motion for 34 of 36 objects of various sizes and periods
      of motion. The 6-s motion required a greater scan time than the 3-s motion for
      equivalent measurement accuracy. The second most influential parameter was the
      target size. For the 3-s period of motion, objects larger than 13 mm were tracked
      with sub-millimeter accuracy with a 1-min scan time. For the 6-s period of
      motion, objects larger than 22-mm were tracked with sub-millimeter accuracy with
      a 1.5-min scan time. For all sizes and motions, temporal blurring was observed
      when the number of phases was fewer than 8. Offset detector configuration
      provided the same performance as centered detector except for small targets (20
      mm.) at short scan times (<=1 min). Finally, reconstruction filtering and number
      of respiratory phases did not affect performance. CONCLUSIONS: Scan time should
      be set according to target size and motion. The authors have provided figures
      that provide the minimum scan time needed to achieve the particular motion
      measurement accuracy for a particular size and motion period.

PMID- 22957635
TI  - Toward truly combined PET/CT imaging using PET detectors and photon counting CT
      with iterative reconstruction implementing physical detector response.
AB  - PURPOSE: This paper intends to demonstrate the feasibility of truly combined
      PET/CT imaging and addresses some of the major challenges raised by this dual
      modality approach. A method is proposed to retrieve maximum accuracy out of
      limited resolution computed tomography (CT) scans acquired with positron emission
      tomography (PET) detectors. METHODS: A PET/CT simulator was built using the
      LabPETTM detectors and front-end electronics. Acquisitions of energy-binned data
      sets were made using this low spatial resolution CT system in photon counting
      mode. To overcome the limitations of the filtered back-projection technique, an
      iterative reconstruction library was developed and tested for the counting mode
      CT. Construction of the system matrix is based on a preregistered raster scan
      from which the experimental detector response is obtained. PET data were obtained
      sequentially with CT in a conventional manner. RESULTS: A meticulous description
      of the system geometry and misalignment corrections is imperative and was
      incorporated into the matrix definition to achieve good image quality. Using this
      method, no sinogram precorrection or interpolation is necessary and measured
      projections can be used as raw input data for the iterative reconstruction
      algorithm. Genuine dual modality PET/CT images of phantoms and animals were
      obtained for the first time using the same detection platform. CONCLUSIONS: CT
      and fused PET/CT images show that LabPETTM detectors can be successfully used as
      individual X-ray photon counting devices for low-dose CT imaging of the anatomy
      in a molecular PET imaging context.

PMID- 22957636
TI  - Differences in predicted and actually absorbed doses in peptide receptor
      radionuclide therapy.
AB  - PURPOSE: An important assumption in dosimetry prior to radionuclide therapy is
      the equivalence of pretherapeutic and therapeutic biodistribution. In this study
      the authors investigate if this assumption is justified in sst2-receptor
      targeting peptide therapy, as unequal amounts of peptide and different peptides
      for pretherapeutic measurements and therapy are commonly used. METHODS:
      Physiologically based pharmacokinetic models were developed. Gamma camera and
      serum measurements of ten patients with metastasizing neuroendocrine tumors were
      conducted using (111)In-DTPAOC. The most suitable model was selected using the
      corrected Akaike information criterion. Based on that model and the estimated
      individual parameters, predicted and measured (90)Y-DOTATATE excretions during
      therapy were compared. The residence times for the pretherapeutic (measured) and
      therapeutic scenarios (simulated) were calculated. RESULTS: Predicted and
      measured therapeutic excretion differed in three patients by 10%, 31%, and 7%.
      The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and
      52%. The simulated therapeutic residence times of kidney and tumor were 3.1 +/-
      0.6 and 2.5 +/- 1.2 fold higher than the measured pretherapeutic ones.
      CONCLUSIONS: To avoid the introduction of unnecessary inaccuracy in dosimetry,
      using the same substance along with the same amount for pretherapeutic
      measurements and therapy is recommended.

PMID- 22957637
TI  - Extra-dimensional Demons: a method for incorporating missing tissue in deformable
      image registration.
AB  - PURPOSE: A deformable registration method capable of accounting for missing
      tissue (e.g., excision) is reported for application in cone-beam CT (CBCT)-guided
      surgical procedures. Excisions are identified by a segmentation step performed
      simultaneous to the registration process. Tissue excision is explicitly modeled
      by increasing the dimensionality of the deformation field to allow motion beyond
      the dimensionality of the image. The accuracy of the model is tested in phantom,
      simulations, and cadaver models. METHODS: A variant of the Demons deformable
      registration algorithm is modified to include excision segmentation and modeling.
      Segmentation is performed iteratively during the registration process, with
      initial implementation using a threshold-based approach to identify voxels
      corresponding to "tissue" in the moving image and "air" in the fixed image. With
      each iteration of the Demons process, every voxel is assigned a probability of
      excision. Excisions are modeled explicitly during registration by increasing the
      dimensionality of the deformation field so that both deformations and excisions
      can be accounted for by in- and out-of-volume deformations, respectively. The out
      of-volume (i.e., fourth) component of the deformation field at each voxel carries
      a magnitude proportional to the excision probability computed in the excision
      segmentation step. The registration accuracy of the proposed "extra-dimensional"
      Demons (XDD) and conventional Demons methods was tested in the presence of
      missing tissue in phantom models, simulations investigating the effect of
      excision size on registration accuracy, and cadaver studies emulating realistic
      deformations and tissue excisions imparted in CBCT-guided endoscopic skull base
      surgery. RESULTS: Phantom experiments showed the normalized mutual information
      (NMI) in regions local to the excision to improve from 1.10 for the conventional
      Demons approach to 1.16 for XDD, and qualitative examination of the resulting
      images revealed major differences: the conventional Demons approach imparted
      unrealistic distortions in areas around tissue excision, whereas XDD provided
      accurate "ejection" of voxels within the excision site and maintained the
      registration accuracy throughout the rest of the image. Registration accuracy in
      areas far from the excision site (e.g., > ~5 mm) was identical for the two
      approaches. Quantitation of the effect was consistent in analysis of NMI,
      normalized cross-correlation (NCC), target registration error (TRE), and accuracy
      of voxels ejected from the volume (true-positive and false-positive analysis).
      The registration accuracy for conventional Demons was found to degrade steeply as
      a function of excision size, whereas XDD was robust in this regard. Cadaver
      studies involving realistic excision of the clivus, vidian canal, and ethmoid
      sinuses demonstrated similar results, with unrealistic distortion of anatomy
      imparted by conventional Demons and accurate ejection and deformation for XDD.
      CONCLUSIONS: Adaptation of the Demons deformable registration process to include
      segmentation (i.e., identification of excised tissue) and an extra dimension in
      the deformation field provided a means to accurately accommodate missing tissue
      between image acquisitions. The extra-dimensional approach yielded accurate
      "ejection" of voxels local to the excision site while preserving the registration
      accuracy (typically subvoxel) of the conventional Demons approach throughout the
      rest of the image. The ability to accommodate missing tissue volumes is important
      to application of CBCT for surgical guidance (e.g., skull base drillout) and may
      have application in other areas of CBCT guidance.

PMID- 22957639
TI  - A novel conformity index for intensity modulated radiation therapy plan
      evaluation.
AB  - PURPOSE: Intensity modulated radiation therapy (IMRT) has gained popularity in
      the treatment of cancers. Manual evaluation of IMRT plans for head-and-neck
      cancers has been especially challenging necessitating efficient and objective
      assessment tools. In this work, the authors address this issue by developing a
      personalized conformity index (CI) for comparison of IMRT plans for head-and-neck
      cancers and evaluating its plan quality discerning power in comparison with other
      widely used CIs. METHODS: A two-dimensional CI with dose and distance
      incorporated (CI(DD)) was developed using the MATLAB program language, to
      quantify the planning target volume (PTV) coverage. Valuable information
      contained in the digital imaging and communication in medicine (DICOM) RT objects
      were harvested for computation of each of the CI(DD) components. Apart from the
      dose penalty factor, a distance-based exponential function was employed by
      varying the penalty weight associated with the location of cold spots within the
      PTV. With the goal of deriving a customized penalty factor, the distances between
      individual pixel and its nearest PTV boundary was found. Using the exponential
      function, the impact of distance penalty was substantially larger for cold spots
      closer to the PTV centroid but petered out quickly wherever they were situated in
      the vicinity of PTV border. In order to evaluate the CI(DD) scoring system, three
      CT image data sets of nasopharyngeal carcinoma (NPC) patients were collected. Ten
      IMRT plans with degrading qualities were generated from each dataset and were
      ranked based on CI(DD) and other existing indices. The coefficient of variance
      was calculated for each dataset to compare the degree of variation. RESULTS: The
      CI(DD) scoring system that considered spatial importance of each voxel within the
      PTV was successfully developed. The results demonstrated that the CI(DD)
      including four discrete factors could provide accurate rankings of plan quality
      by examining the relative importance of each cold spot within the PTVs. Apart
      from the dose penalty factor, a distance-based exponential function was employed
      taking the specific tumor geometry into account. Compared with other commonly
      used CIs, the CI(DD) resulted in the largest coefficient of variance among the
      ten IMRT plans for each dataset, indicating that its discerning power was the
      best among the CIs being compared. CONCLUSIONS: The CI(DD) scoring system was
      successfully developed to incorporate patient-specific spatial dose information
      and provide a geometry-based physical index for comparison of IMRT plans for head
      and-neck cancers. By taking individual tumor geometry into account, the
      superiority of CI(DD) in plan discerning power was demonstrated. The use of
      CI(DD) could provide an effective means of benchmarking performance, reducing
      treatment plan variability, and advancing the quality of current IMRT planning.

PMID- 22957638
TI  - Ultrasound GLCM texture analysis of radiation-induced parotid-gland injury in
      head-and-neck cancer radiotherapy: an in vivo study of late toxicity.
AB  - PURPOSE: Xerostomia (dry mouth), secondary to irradiation of the parotid glands,
      is one of the most common side effects of head-and-neck cancer radiotherapy.
      Diagnostic tools able to accurately and efficiently measure parotid gland injury
      have yet to be introduced into the clinic. This study's purpose is to investigate
      sonographic textural features as potential imaging signatures for quantitative
      assessment of parotid-gland injury after head-and-neck radiotherapy. METHODS: The
      authors have investigated a series of sonographic features obtained from the gray
      level co-occurrence matrix (GLCM) - a second order statistical method of texture
      analysis. These GLCM textural features were selected based on empirical
      observations that the normal parotid gland exhibits homogeneous echotexture,
      whereas the postradiotherapy parotid gland often exhibits heterogeneous
      echotexture. We employed eight sonographic features: (1) angular second moment
      (ASM), (2) inverse differential moment (IDM), (3) contrast, (4) variance, (5)
      correlation, (6) entropy, (7) cluster shade, and (8) cluster prominence.
      Altogether, sonographic properties of the parotid glands were quantified by their
      degrees of homogeneity (ASM and IDM), heterogeneity (contrast and variance),
      smoothness (correlation), randomness (entropy), and symmetry (cluster shade and
      prominence). The sonographic features were tested in a pilot study of 12
      postradiotherapy patients and 7 healthy volunteers. The mean follow-up time for
      the postradiotherapy patients was 17.2 months (range: 12.1-23.9 months) and the
      mean radiation dose to the parotid glands was 32.3 Gy (range: 11.0-63.4 Gy). Each
      participant underwent one ultrasound study in which longitudinal (vertical)
      ultrasound scans were performed on the bilateral parotids - a total of 24
      postirradiation and 14 normal parotid glands were examined. The 14 normal parotid
      glands served as the control group. A radiologist contoured the parotid glands on
      the B-mode images and the sonographic features were computed from the contoured
      region-of-interest. RESULTS: The authors observed significant differences (p <
      0.05) in all sonographic features between the normal and postradiotherapy parotid
      glands. The sonographic findings were consistent with the clinical observations
      of the ultrasound images: normal parotid glands exhibited homogeneous texture,
      while the postradiotherapy parotid glands exhibited heterogeneous echotexture
      (e.g., hyperechoic lines and spots), which likely represents fibrosis.
      CONCLUSIONS: The authors have demonstrated the feasibility of ultrasonic texture
      evaluation of parotid glands; and the sonographic features may serve as imaging
      signatures to assess radiation-induced parotid injury.

PMID- 22957640
TI  - Reference standard and statistical model for intersite and temporal comparisons
      of CT attenuation in a multicenter quantitative lung study.
AB  - PURPOSE: The purpose of this study was to detect and analyze anomalies between a
      large number of computed tomography (CT) scanners, tracked over time, utilized to
      collect human pulmonary CT data for a national multicenter study: chronic
      obstructive pulmonary disease genetic epidemiology study (COPDGene). METHODS: A
      custom designed CT reference standard "Test Object" has been developed to
      evaluate the relevant differences in CT attenuation between CT scanners in
      COPDGene. The materials used in the Test Object to assess CT scanner accuracy and
      precision included lung equivalent foam (-856 HU), internal air (-1000 HU), water
      (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were
      manufactured. Initially, all Test Objects were scanned on the same CT scanner
      before the Test Objects were sent to the 20 specific sites and 42 individual CT
      scanners that were used in the study. The Test Objects were scanned over 17
      months while the COPDGene study continued to recruit subjects. A mixed linear
      effect statistical analysis of the CT scans on the 19 Test Objects was performed.
      The statistical model reflected influence of reconstruction kernels, tube
      current, individual Test Objects, CT scanner models, and temporal consistency on
      CT attenuation. RESULTS: Depending on the Test Object material, there were
      significant differences between reconstruction kernels, tube current, individual
      Test Objects, CT scanner models, and temporal consistency. The two Test Object
      materials of most interest were lung equivalent foam and internal air. With lung
      equivalent foam, there were significant (p < 0.05) differences between the
      Siemens B31 (-856.6, +/-0.82; mean +/- SE) and the GE Standard (-856.6 +/- 0.83)
      reconstruction kernel relative to the Siemens B35 reference standard (-852.5 +/-
      1.4). Comparing lung equivalent foam attenuation there were also significant
      differences between CT scanner models (p < 0.01), tube current (p < 0.005), and
      in temporal consistency (p < 0.005) at individual sites. However, there were no
      significant effects measurable using different examples of the Test Objects at
      the various sites compared to the reference scans of the 19 Test Objects. For
      internal air, significant (p < 0.005) differences were found between all
      reconstruction kernels (Siemens B31, GE Standard, and Phillips B) compared to the
      reference standard. There were significant differences between CT models (p <
      0.005), and tube current (p < 0.005). There were no significant effects
      measurable using different examples of the Test Objects at the various sites
      compared to the reference scans of the 19 Test Objects. Differences, across
      scanners, between external air and internal air measures in this simple (relative
      to the in vivo lung) test object varied by as much as 15 HU. CONCLUSIONS: The
      authors conclude that the Test Object designed for this study was able to detect
      significant effects regarding individual CT scanners that altered the CT
      attenuation measurements relevant to the study that are used to determine lung
      density. Through an understanding of individual scanners, the Test Object
      analysis can be used to detect anomalies in an individual CT scanner and to
      statistically model out scanner differences and individual scanner changes over
      time in a large multicenter trial.

PMID- 22957641
TI  - Emerging technologies for image guidance and device navigation in interventional
      radiology.
AB  - Recent developments in image-guidance and device navigation, along with emerging
      robotic technologies, are rapidly transforming the landscape of interventional
      radiology (IR). Future state-of-the-art IR procedures may include real-time three
      dimensional imaging that is capable of visualizing the target organ,
      interventional tools, and surrounding anatomy with high spatial and temporal
      resolution. Remote device actuation is becoming a reality with the introduction
      of novel magnetic-field enabled instruments and remote robotic steering systems.
      Robots offer several degrees of freedom and unprecedented accuracy, stability,
      and dexterity during device navigation, propulsion, and actuation. Optimization
      of tracking and navigation of interventional tools inside the human body will be
      critical in converting IR suites into the minimally invasive operating theaters
      of the future with increased safety and unsurpassed therapeutic efficacy. In the
      not too distant future, individual image guidance modalities and device tracking
      methods could merge into autonomous, multimodality, multiparametric platforms
      that offer real-time data of anatomy, morphology, function, and metabolism along
      with on-the-fly computational modeling and remote robotic actuation. The authors
      provide a concise overview of the latest developments in image guidance and
      device navigation, while critically envisioning what the future might hold for
      2020 IR procedures.

PMID- 22957642
TI  - Comment on "estimation of organ and effective dose due to Compton backscatter
      security scans" [Med. Phys. 39, 3396 (2012)].

PMID- 22957647
TI  - Retinoblastoma gene-independent G1 phase arrest by flavone, phosphatidylinositol
      3-kinase inhibitor, and histone deacetylase inhibitor.
AB  - In most human malignant tumors, retinoblastoma tumor-suppressor gene (RB) product
      is inactivated by phosphorylation. Therefore, cancer preventive agents or
      molecular-targeting agents can inhibit the tumor growth at G(1)  phase through RB
      reactivation. However, little is known about the effectiveness of RB reactivating
      agents against malignancies with mutated RB. We report here that chemopreventive
      agent flavone, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, and
      histone deacetylase (HDAC) inhibitor trichostatin A (TSA) also induce G(1)  phase
      arrest in malignant tumor cells with mutated RB. In human prostate cancer DU145
      cells with mutated RB, flavone increased cyclin-dependent kinase (CDK) inhibitors
      p21 and p27, and reduced cdk4 and cdk6, resulting in decrement of phosphorylated
      RB family proteins p130 and p107. LY294002 also dephosphorylated p107 and p130
      proteins, whereas TSA dephosphorylated p130, but not p107. Furthermore, flavone
      induced G(1)  phase arrest in both mouse embryo fibroblast (MEF) wild-type and
      MEF RB(-/-)  cells, but did not do so in RB, p107, and p130 triple-knockout MEF
      cells. These results suggested that p130 and p107 contributed to G(1)  phase
      arrest by flavone in RB-mutated cells. However, flavone induced tumor suppressor
      microRNA miR-34a with reduction of E2F1 and E2F3, known to be downregulated by
      miR-34a, raising the possibility that miR-34a might partially contribute to G(1) 
      arrest by flavone. These results raise the possibility that RB reactivating
      chemopreventive agents or molecular targeting agents might also be effective
      against a variety of malignant tumor cells with mutant RB.

PMID- 22957648
TI  - Enhanced immunological response by dendritic cells in male hypogonadism.
AB  - BACKGROUND: The effect of male hypogonadism on the immune response is poorly
      understood, even though testosterone has both immunosuppressive and anti
      inflammatory effects in men. DESIGN: In this study, we compared the distribution
      and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs)
      [CD16(+) (monocytoid), CD33(+) (myeloid) and CD33(-) (plasmacytoid)] and CD4(+)
      CD25(+)CD127(-/lo) regulatory T cells from hypogonadic men and control subjects.
      Immunophenotypic studies were performed both on resting and in vitro-stimulated
      cells. RESULTS: Overall, no significant differences were detected on the number
      of monocytes, DCs and CD4(+) CD25(+) CD127(-/lo) regulatory T cells between both
      groups of subjects. However, hypogonadic men showed slightly higher numbers of
      circulating CD16(+) cells expressing the CD107b activation/degranulation
      associated marker than controls, such differences reaching statistical
      significance after in vitro stimulation with CpG oligodeoxynucleotides.
      Interestingly, antigen-stimulated expression of CD107b on CD16(+) cells inversely
      correlated with the serum concentrations of total testosterone (r(2)=-0.45;
      P=0.01), free testosterone (r(2)=-0.48; P=0.005), calculated free testosterone
      (r(2)=-0.44; P=0.01) and bioavailable testosterone (r(2)=-0.46; P=0.008) among
      all cases studied, as well as with both the LH (r(2)=-0.53, P=0.04) and FSH
      (r(2)=-0.54, P=0.04) serum levels among hypogonadic men. CONCLUSIONS: These
      findings show an enhanced immunological response of circulating (activated)
      CD16(+) DCs to antigen stimulation, which was inversely related to testosterone
      and gonadotropin serum levels. Such findings suggest a modulation by the
      hypothalamic-hypophyseal-gonadal axis of the immune response and may have
      clinical implications for hypogonadic men, as regards susceptibility to
      autoimmune diseases and increased responses to antigenic stimuli.

PMID- 22957649
TI  - A new stonefly species, Rhopalopsole tricuspis (Leuctridae: Plecoptera), and
      three new records of stoneflies from the Qinling Mountains of Shaanxi, China.
AB  - Plecopteran species (Leuctridae) were collected from the Qinling Mountains in
      southern Shaanxi Province, China. This mountain range is home to nine species of
      Leuctridae belonging to two genera, and the species identified in this work
      include one new species and three new records for the Qinling Mountains, all
      belonging to the genus Rhopalopsole. The new species is named R. tricuspis Qian
      and Du, sp. nov. A redescription of R. basinigra Yang and Yang 1995 is
      supplemented. A key is provided for the adult males of Leuctridae from the
      Qinling Mountains.

PMID- 22957650
TI  - Channel length scaling of MoS2 MOSFETs.
AB  - In this article, we investigate electrical transport properties in ultrathin body
      (UTB) MoS(2) two-dimensional (2D) crystals with channel lengths ranging from 2
      MUm down to 50 nm. We compare the short channel behavior of sets of MOSFETs with
      various channel thickness, and reveal the superior immunity to short channel
      effects of MoS(2) transistors. We observe no obvious short channel effects on the
      device with 100 nm channel length (L(ch)) fabricated on a 5 nm thick MoS(2) 2D
      crystal even when using 300 nm thick SiO(2) as gate dielectric, and has a current
      on/off ratio up to ~10(9). We also observe the on-current saturation at short
      channel devices with continuous scaling due to the carrier velocity saturation.
      Also, we reveal the performance limit of short channel MoS(2) transistors is
      dominated by the large contact resistance from the Schottky barrier between Ni
      and MoS(2) interface, where a fully transparent contact is needed to achieve a
      high-performance short channel device.

PMID- 22957651
TI  - Stereoselective synthesis of S-linked alpha(2->8) and alpha(2->8)/alpha(2->9)
      hexasialic acids.
AB  - A new approach for the synthesis of S-linked alpha(2->8) and alternating alpha(2
      >8)/alpha(2->9) oligosialic acids by S-alkylation has been developed, using chemo
      and stereoselective alkylation of a C2-thiolated sialoside donor (nucleophile)
      with either a C8- or C9-iodide-activated sialoside acceptor (electrophile). An
      efficient intramolecular acetyl group migration from the C7 to C9-position of the
      sialoside under mild basic conditions was used to generate the C8-iodide, the key
      sialyl acceptor (electrophile). Using this strategy, the syntheses of S-linked
      alpha(2->8) and alpha(2->8)/alpha(2->9) hexasialic acids were achieved.

PMID- 22957652
TI  - Streptococcus agalactiae late-onset neonatal infections: should breast milk be
      more systematically tested for bacterial contamination?

PMID- 22957653
TI  - Spectroelectrochemical characterization of small hemoproteins adsorbed within
      nanostructured mesoporous ITO electrodes.
AB  - 3D nanostructured transparent indium tin oxide (ITO) electrodes prepared by
      glancing angle deposition (GLAD) were used for the spectroelectrochemical
      characterization of cytochrome c (Cyt c) and neuroglobin (Nb). These small
      hemoproteins, involved as electron-transfer partners in the prevention of
      apoptosis, are oppositely charged at physiological pH and can each be adsorbed
      within the ITO network under different pH conditions. The resulting modified
      electrodes were investigated by UV-visible absorption spectroscopy coupled with
      cyclic voltammetry. By using nondenaturating adsorption conditions, we
      demonstrate that both proteins are capable of direct electron transfer to the
      conductive ITO surface, sharing apparent standard potentials similar to those
      reported in solution. Preservation of the 3D protein structure upon adsorption
      was confirmed by resonance Raman (rR) spectroscopy. Analysis of the derivative
      cyclic voltabsorptograms (DCVA) monitored either in the Soret or the Q bands at
      scan rates up to 1 V s(-1) allowed us to investigate direct interfacial electron
      transfer kinetics. From the DCVA shape and scan rate dependences, we conclude
      that the interaction of Cyt c with the ITO surface is more specific than Nb,
      suggesting an oriented adsorption of Cyt c and a random adsorption of Nb on the
      ITO surface. At the same time, Cyt c appears more sensitive to the experimental
      adsorption conditions, and complete denaturation of Cyt c may occur as evidenced
      from cross-correlation of rR spectroscopy and spectroelectrochemistry.

PMID- 22957654
TI  - Radioactive iodine ablation does not prevent recurrences in patients with
      papillary thyroid microcarcinoma.
AB  - OBJECTIVE: Although papillary thyroid microcarcinoma (PTMC) has a favourable long
      term prognosis, disease recurrence after initial treatment remains a problem and
      controversy exists regarding the role of radioactive iodine (RAI) ablation in
      PTMC. We performed this study to evaluate the effect of RAI ablation on disease
      recurrence in patients with PTMC. PATIENTS AND METHODS: Between 1994 and 2004,
      2579 patients underwent thyroid surgery for thyroid cancer at Samsung Medical
      Center. Among these patients, 704 patients with PTMC presumed disease-free after
      initial treatment were followed up for disease recurrence (median, 64 months;
      range, 1-185 months). Patients with PTMC with microscopic extrathyroidal
      extension, cervical lymph node metastases or multifocality were considered to be
      in the intermediate-risk group for recurrence. RESULTS: Disease recurrence was
      found in six patients at a median of 29 months (range, 10-70 months) after
      initial treatment; all six patients with recurrent tumours had received RAI
      treatment after total thyroidectomy. Disease-related mortality was not observed,
      even after recurrence. Based on a Cox regression model considering the
      standardized inverse probability of treatment weight (IPTW) within each
      propensity score stratum of patients with a similar likelihood of having received
      RAI ablation, the likelihood ratio for recurrence did not differ between the RAI
      ablation group and no RAI group (P = 0.17). When we performed a subgroup analysis
      considering only patients with PTMC at intermediate-risk for recurrence, RAI
      ablation again did not have a significant effect on recurrence (P = 0.79).
      CONCLUSIONS: Radioactive iodine ablation after total thyroidectomy in low- and
      intermediate-risk patients with PTMC did not prevent recurrent tumours. Future
      randomized, controlled, multicenter prospective trials involving a larger sample
      of patients followed-up for a longer duration are warranted to confirm our
      findings.

PMID- 22957655
TI  - Hydrogen abstraction from cyclic amines by the cumyloxyl and benzyloxyl radicals.
      The role of stereoelectronic effects and of substrate/radical hydrogen bonding.
AB  - A kinetic study on the hydrogen abstraction reactions from cyclic amines and
      diamines (pyrrolidines, piperidines, morpholines, and piperazines) by the
      cumyloxyl (CumO(*)) and benzyloxyl (BnO(*)) radicals was carried out. The
      reactions with CumO(*) were described in all cases as direct hydrogen
      abstractions. The differences in the hydrogen abstraction rate constant (k(H))
      were explained in terms of the different number of abstractable hydrogen atoms,
      the operation of stereoelectronic effects, and, with the morpholines, on the
      basis of polar effects. Significantly higher k(H) values were measured for the
      reactions of the amines with BnO(*). This behavior was explained on the basis of
      a mechanism that proceeds through the rate-determining formation of a hydrogen
      bonded pre-reaction complex between the radical alpha-C-H and the nitrogen lone
      pair followed by hydrogen abstraction within the complex. A decrease in k(H) was
      observed going from secondary to tertiary amines and, with tertiary amines, on
      increasing steric hindrance at nitrogen, pointing toward the important role of
      steric and electronic effects on pre-reaction complex formation. These results
      expand previous findings contributing to a detailed mechanistic description of
      the reactions of alkoxyl radicals with amines, showing that structural effects in
      both the substrate and the radical can play a dramatic role and providing new
      information on the role of substrate/radical interactions on these processes.

PMID- 22957656
TI  - Current status and future prospects for cultured limbal tissue transplants in
      Australia and New Zealand.
AB  - Cultured limbal tissue transplants have become widely used over the last decade
      as a treatment for limbal stem cell deficiency (LSCD). While the number of
      patients afflicted with LSCD in Australia and New Zealand is considered to be
      relatively low, the impact of this disease on quality of life is so severe that
      the potential efficacy of cultured transplants has necessitated investigation. We
      presently review the basic biology and experimental strategies associated with
      the use of cultured limbal tissue transplants in Australia and New Zealand. In
      doing so, we aim to encourage informed discussion on the issues required to
      advance the use of cultured limbal transplants in Australia and New Zealand.
      Moreover, we propose that a collaborative network could be established to
      maintain access to the technology in conjunction with a number of other existing
      and emerging treatments for eye diseases.

PMID- 22957657
TI  - Relationships between fertility and some parameters in male broiler breeders
      (body and testicular weight, histology and immunohistochemistry of testes,
      spermatogenesis and hormonal levels).
AB  - In a farm of grandparent broiler breeder chickens, we followed the development of
      350 roosters from 6 to 55 weeks of age. Data collected and evaluated from these
      males included body weight, testicular weight, histologic and
      immunohistochemistry studies of the testes, hormone levels (testosterone,
      estradiol and corticosterone) and sperm production. The objective was to
      understand the factors that affect or influence hatch loss that is commonly
      observed after 45 weeks of age in breeder flocksare often correlated to broiler
      breeder male chickens. The results of this study showed that in conjunction with
      the weight of the rooster, the testicle weight increases quickly after the
      rooster receives light stimulation. At an older age, the study showed that there
      is a process of testicular shrinkage, and the same effect is seen in sperm
      production and testosterone levels in broiler breeder roosters. From the
      histology evaluation, we defined 5 histologic phases that illustrate the
      evolution of the testicular tissue: perinatal, infantile, puberty, adult and
      senile. We observed that the adult males with a body weight <3800 g were
      infertile or had subfertile levels and also had low levels of testosterone and
      high levels of corticosterone. In contrast, the heaviest males showed correct
      testicular vitality, high levels of testosterone and low levels of
      corticosterone. However, the roosters that had acquired this high body weight
      were also at risk of having less complete copulations because of their physical
      mass. The loss of uniformity of the males and the appearance of hierarchies
      within the flock accompany a decline in the percentages of hatches as a
      consequence of the poor confirmation of the males for copulation or the
      restriction to the access to the females. Results of this study show that the
      decrease in fertility from 45 weeks of age has been associated with a decline in
      testicular weight, sperm production and the testosterone levels in animals with a
      sub-par weight. Likewise, decreasing hatch in older flocks may also result from a
      loss of conformation, and the lack of complete copulations is possible because of
      animals that are grossly overweight.

PMID- 22957658
TI  - Synthesis of a Fe(II)SH complex stabilized by an intramolecular N-H...S hydrogen
      bond, which acts as a H2S donor.
AB  - Through use of the reversible protonation of an iron(II) complex containing a
      deprotonated carboxamido moiety, we prepared and fully characterized the first
      hydrogen(sulfido)iron(II) complex stabilized by an intramolecular hydrogen bond,
      which acts as a H(2)S donor in solution.

PMID- 22957659
TI  - Performance at different stimulus intensities with the within- and across-channel
      adaptive tests of temporal resolution.
AB  - OBJECTIVE: The Adaptive Tests of Temporal Resolution (ATTR(c)) software provides
      within-channel (WC) and across-channel (AC) adaptive measures of temporal
      resolution that are feasible for clinical applications. The purpose of the
      present study was to obtain normative values for young adults on two of the ATTR
      tests: the narrow-band noise within-channel (NBN-WC) test and the narrow-band
      noise across-channel (NBN-AC) test, at different stimulus intensities. DESIGN:
      Gap detection thresholds were measured at five sensation levels. A Latin square
      design was used to control for practice effects. STUDY SAMPLE: The NBN-WC group
      and the NBN-AC group each consisted of 25 young adults with normal hearing.
      RESULTS: Gap detection thresholds for both conditions decreased with increasing
      stimulus intensity, and stimulus intensities above 20 dB SL were not associated
      with large improvements in performance. Variability was larger in the NBN-AC
      condition. Values obtained for the NBC-WC condition were very similar to
      previously reported ATTR results despite equipment and design differences.
      CONCLUSION: Results provide normative values for NBN-WC and NBN-AC performance on
      the ATTR and suggest that the ATTR is a robust test for clinical use.

PMID- 22957660
TI  - Robot-assisted partial nephrectomy: off-clamp technique.
AB  - Robot-assisted partial nephrectomy (RAPN) has been established as a viable
      alternative to open and laparoscopic partial nephrectomy for small renal tumors.
      Multiple variations in surgical technique have been described to reduce warm
      ischemia time (WIT). We present our off-clamp technique for RAPN. From August
      2007 to January 2012, off-clamp RAPN was performed on 47 tumors in 39 patients.
      WIT was 0 minutes in all cases. The mean operative time was 147 minutes (SD=58);
      the mean and median estimated blood loss were 219 mL (SD=253) and 150 mL (range
      50-1500), respectively; the mean length of stay was 1.9 days (SD=1.1). There were
      no intraoperative complications, and results for all surgical margins were
      negative. In experienced hands, our off-clamp technique for RAPN is a safe and
      feasible technique that eliminates WIT.

PMID- 22957661
TI  - Environmental and demographic risk factors for egg allergy in a population-based
      study of infants.
AB  - BACKGROUND: Although egg allergy is the most common food allergy in infants and
      young children, risk factors for egg allergy remain largely unknown. This study
      examined the relationship between environmental and demographic factors and egg
      allergy in a population-based infant cohort. METHODS: In a study of 5276 infants
      (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12
      months of age. Questionnaire data on relevant exposures were obtained. 699/873
      (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended
      for formal assessment of egg allergy status; 453 had confirmed egg allergy
      (positive challenge and SPT >= 2 mm). Associations between environmental and
      demographic factors and egg allergy were investigated using multivariable
      logistic regression. RESULTS: Children with older siblings and those with a pet
      dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR
      [aOR], 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99,
      respectively). Caesarean section delivery, antibiotic use in infancy, childcare
      attendance and maternal age were not associated with egg allergy. History of
      allergic disease in an immediate family member and having parents born in East
      Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40,
      2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively). CONCLUSIONS: Exposure in
      the first year of life to siblings and dogs may decrease the risk of subsequent
      egg allergy. Infants with a family history of allergy and those with parents born
      in East Asia are at increased risk of egg allergy.

PMID- 22957662
TI  - Factors associated with suicide ideation in severely obese bariatric surgery
      seeking individuals.
AB  - There are high rates of suicide ideation and/or behavior in severely obese
      individuals. The potential contributors to suicide ideation in a sample of 334
      severely obese bariatric surgery candidates was explored. Lack of college
      education, a history of suicide ideation and/or behavior, psychological distress,
      hopelessness, loneliness, history of physical and/or sexual abuse, and lifetime
      major depression were associated with current suicide ideation. Some of the
      correlates of suicide ideation in severely obese bariatric surgery-seeking
      samples are similar to those found in the general community and this knowledge
      may serve to improve the psychological assessment and care for this group.

PMID- 22957663
TI  - Role of glycosphingolipids in the function of human serotonin1A receptors.
AB  - Glycosphingolipids are essential components of eukaryotic cell membranes and are
      involved in the regulation of cell growth, differentiation, and neoplastic
      transformation. In this work, we have modulated glycosphingolipid levels in CHO
      cells stably expressing the human serotonin(1A)  receptor by inhibiting the
      activity of glucosylceramide synthase using (+/-)-threo-1-phenyl-2-decanoylamino
      3-morpholino-1-propanol (PDMP), a commonly used inhibitor of the enzyme.
      Serotonin(1A)  receptors belong to the family of G-protein-coupled receptors and
      are implicated in the generation and modulation of various cognitive, behavioral,
      and developmental functions. We explored the function of the serotonin(1A) 
      receptor under glycosphingolipid-depleted condition by monitoring ligand-binding
      activity and G-protein coupling of the receptor. Our results show that ligand
      binding of the receptor is impaired under these conditions although the
      efficiency of G-protein coupling remains unaltered. The expression of the
      receptor at the cell membrane appears to be reduced. Interestingly, our results
      show that the effect of glycosphingolipids on ligand binding caused by metabolic
      depletion of these lipids is reversible. These novel results demonstrate that
      glycosphingolipids are necessary for the function of the serotonin(1A)  receptor.
      We discuss possible mechanisms of specific interaction of glycosphingolipids with
      the serotonin(1A)  receptor that could involve the proposed 'sphingolipid-binding
      domain'.

PMID- 22957664
TI  - Crystalline keratopathy associated with monoclonal gammopathy of undetermined
      significance.

PMID- 22957665
TI  - Myxomas in all cardiac chambers.

PMID- 22957667
TI  - Use of nitinol stents for end-stage tracheal collapse in dogs.
AB  - OBJECTIVE: To report bronchoscopic placement of nitinol stents (Vet Stent
      Trachea(r)) for improvement of end-stage clinical signs in dogs with tracheal
      collapse. STUDY DESIGN: Case series. SAMPLE POPULATION: Dogs (n = 18). METHODS:
      Medical records (January 1, 2004-October 31, 2008) were searched for dogs with a
      diagnosis of tracheal collapse; 18 dogs met inclusion criteria. Tracheal diameter
      was compared before and after stent deployment. Stent dimensions were compared
      after stent deployment and at radiographic follow-up. RESULTS: There was a
      significant difference in the minimum tracheal diameter when initial and post
      deployment tracheal diameters were compared (P = .003). Stent length was
      significantly shorter at follow-up when compared to post deployment measurements
      (P = .004). Owner assessment of outcome was available for all dogs with 11.1%
      mortality within 60 days. Complications were documented in 9 dogs. CONCLUSIONS:
      Use of a nitinol stent (Vet Stent-Trachea(r)) in dogs with end-stage tracheal
      collapse is associated with a fair to good outcome despite significant temporal
      stent fore shortening after bronchoscopic placement.

PMID- 22957669
TI  - Association of dietary and genetic factors related to one-carbon metabolism with
      global methylation level of leukocyte DNA.
AB  - Global hypomethylation of leukocyte DNA has been associated with an increased
      risk of cancer. As dietary and genetic factors related to one-carbon metabolism
      may influence both the methylation and synthesis of DNA, we investigated
      associations between these factors and the global methylation level of peripheral
      blood leukocyte DNA based on a cross-sectional study of 384 Japanese women.
      Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a
      validated semiquantitative food frequency questionnaire. Five polymorphisms in
      methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine
      synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and
      rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified
      using Luminometric Methylation Assay. A linear trend of association between
      methylation and dietary and genetic factors was evaluated by regression
      coefficients in a multivariable linear regression model. Mean global methylation
      level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%.
      Global methylation level significantly decreased by 0.36% (95% confidence
      interval, 0.03-0.69) per quartile category for folate level. Subgroup analysis
      suggested that alcohol drinking modified the association between folate intake
      and global methylation level (P(interaction)  = 0.01). However, no statistically
      significant association was observed for intake of vitamins B2, B6, and B12,
      alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and
      MTRR. We found that higher folate intake was significantly associated with a
      lower level of global methylation of leukocyte DNA in a group of healthy Japanese
      females.

PMID- 22957670
TI  - Child development at 5 years of age predicted mathematics ability and schooling
      outcomes in Malawian adolescents.
AB  - AIM: This study aimed to examine the association between child development at 5
      years of age and mathematics ability and schooling outcomes at 12 years of age in
      Malawian children. METHODS: A prospective cohort study looking at 609 rural
      Malawian children. Outcome measures were percentage of correctly answered
      mathematics questions, highest school grade completed and number of times
      repeating school grades at 12 years of age. A child development summary score
      obtained at 5 years of age was the main exposure variable. Regression analyses
      were used to estimate the association and adjust for confounders. Sensitivity
      analysis was performed by handling losses to follow-up with multiple imputation
      (MI) method. RESULTS: The summary score was positively associated with percentage
      of correctly answered mathematics questions (p = 0.057; p = 0.031 MI) and with
      highest school grade completed (p = 0.096; p = 0.070 MI), and negatively
      associated with number of times repeating school grades (p = 0.834; p = 0.339
      MI). Fine motor score at 5 years was independently associated with the mathematic
      score (p = 0.032; p = 0.011 MI). The association between child development and
      mathematics ability did not depend on school attendance. CONCLUSION: Child
      development at 5 years of age showed signs of positive association with
      mathematics ability and possibly with highest school grade completed at 12 years
      of age.

PMID- 22957668
TI  - Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet
      autoantibodies in childhood and adolescent type 1 diabetes.
AB  - OBJECTIVE: To establish the diagnostic sensitivity of and the relationships
      between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8
      autoantibody to either one, two, or all three amino acid variants at position
      325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to
      glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and
      insulin (IAA). METHODS: We analyzed 3165 patients with type 1 diabetes (T1D) in
      the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six
      autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA,
      tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc
      transporter 8 autoantibody; GADA, IA-2A, and IAA). RESULTS: ZnT8A was found in
      65% of the patients and as many as 108 of 3165 (3.4%) had 1-3 ZnT8A alone. None
      had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of
      the T1D patients were autoantibody positive. All three ZnT8A were less frequent
      in children below 2 yr of age (p < 0.0001). All three ZnT8A were associated with
      DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were
      negatively associated with DQA1-B1*05-02 (DQ2). CONCLUSIONS: Analysis of ZnT8A
      increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7%
      remained islet autoantibody negative. The association between DQ6.4 and all three
      ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.

PMID- 22957671
TI  - Growth of in situ functionalized luminescent silver nanoclusters by direct
      reduction and size focusing.
AB  - We have used one phase growth reaction to prepare a series of silver
      nanoparticles (NPs) and luminescent nanoclusters (NCs) using sodium borohydride
      (NaBH(4)) reduction of silver nitrate in the presence of molecular scale ligands
      made of polyethylene glycol (PEG) appended with lipoic acid (LA) groups at one
      end and reactive (-COOH/-NH(2)) or inert (-OCH(3)) functional groups at the other
      end. The PEG segment in the ligand promotes solubility in a variety of solvents
      including water, while LAs provide multidentate coordinating groups that promote
      Ag-ligand complex formation and strong anchoring onto the NP/NC surface. The
      particle size and properties were primarily controlled by varying the Ag-to
      ligand (Ag:L) molar ratios and the molar amount of NaBH(4) used. We found that
      while higher Ag:L ratios produced NPs, luminescent NCs were formed at lower
      ratios. We also found that nonluminescent NPs can be converted into luminescent
      clusters, via a process referred to as "size focusing", in the presence of added
      excess ligands and reducing agent. The nanoclusters emit in the far red region of
      the optical spectrum with a quantum yield of ~12%. They can be redispersed in a
      number of solvents with varying polarity while maintaining their optical and
      spectroscopic properties. Our synthetic protocol also allowed control over the
      number and type of reactive functional groups per nanocluster.

PMID- 22957673
TI  - Aesthetics, ambience, and institutional health care environments.

PMID- 22957674
TI  - Palliative care for an Islamic patient: changing frameworks.

PMID- 22957675
TI  - Alleviating dyspnea and possible biologic mechanisms.

PMID- 22957676
TI  - ESAS, CABG, and the personal experience of two palliative clinicians.

PMID- 22957677
TI  - Attitudes and perceptions of patients, caregivers, and health care providers
      toward background music in patient care areas: an exploratory study.
AB  - BACKGROUND: Background music can be used to distract from ordinary sounds and
      improve wellbeing in patient care areas. Little is known about individuals'
      attitudes and beliefs about music versus ordinary sound in this setting.
      OBJECTIVES: To assess the preferences of patients, caregivers and healthcare
      providers regarding background music or ordinary sound in outpatient and
      inpatient care areas, and to explore their attitudes and perceptions towards
      music in general. METHODS: All participants were exposed to background music in
      outpatient or inpatient clinical settings. 99 consecutive patients, 101
      caregivers and 65 out of 70 eligible healthcare providers (93%) completed a
      survey about music attitudes and preferences. The primary outcome was a
      preference for background music over ordinary sound in patient care areas.
      RESULTS: Preference for background music was high and similar across groups (70
      patients (71%), 71 caregivers (71%) and 46 providers (71%), p=0.58). The three
      groups had very low disapproval for background music in patient care areas (10%,
      9% and 12%, respectively; p=0.91). Black ethnicity independently predicted lower
      preference for background music (OR: 0.47, 95%CI: 0.23, 0.98). Patients,
      caregivers and providers reported recent use of music for themselves for the
      purpose of enjoyment (69%, 80% and 86% respectively p=0.02). Age, gender,
      religion and education level significantly predicted preferences for specific
      music styles. CONCLUSION: Background music in patient care areas was preferred to
      ordinary sound by patients, caregivers and providers. Demographics of the
      population are strong determinants of music style preferences.

PMID- 22957679
TI  - Vertebroplasty and kyphoplasty for vertebral compression fractures #202.

PMID- 22957678
TI  - African American bereaved family members' perceptions of hospice quality: do
      hospices with high proportions of African Americans do better?
AB  - BACKGROUND: Research suggests that racial differences in end-of-life care persist
      even among patients enrolled in hospice. OBJECTIVE: The objective of the study
      was to examine the association between bereaved family members' satisfaction with
      hospice services and the proportion of African American (AA) patients in hospice.
      METHODS: The 2007 and 2008 Family Evaluation of Hospice Care (FEHC) Survey
      examined family members' perceptions of the quality of care on several dimensions
      including: unmet need for pain, dyspnea, and emotional support; being informed
      about the patient's condition and what to expect as the patient was dying; being
      informed about medications and treatments for symptoms; coordination of care; and
      overall satisfaction with care. We examined the association between family
      members' perception along each domain and the proportion of AAs served by
      hospices surveyed. RESULTS: Of the 11,892 AA decedents in 678 hospice programs,
      53.7% were female. The leading cause of death was cancer (51.6%). On univariate
      analysis, family members of decedents who died in hospices that had higher
      proportions of AAs were less likely to have concerns about unmet pain needs (odds
      ratio [OR] 0.84, 95% confidence interval [CI] 0.72-0.98), more likely to have
      concerns about coordination of care (1.28, 1.17-1.40), and less likely to
      perceive care as excellent or very good (0.73, 0.63-0.84). Coordination-of-care
      concerns and lower overall rating of care persisted in multivariable analyses.
      There were no other significant associations between family perceptions and
      proportions of AAs in hospice. CONCLUSIONS: Among hospices with higher
      proportions of AAs, family members have more concerns about coordination of care
      and have lower overall perceptions of quality.

PMID- 22957680
TI  - Diabetes management at the end of life #258.

PMID- 22957682
TI  - While there's life, there's hope: a memorable tale from my trainee years.

PMID- 22957686
TI  - Natural history of the Neotropical arboreal ant, Odontomachus hastatus: nest
      sites, foraging schedule, and diet.
AB  - The ecology of most arboreal ants remains poorly documented because of the
      difficulty in accessing ant nests and foragers in the forest canopy. This study
      documents the nesting and foraging ecology of a large (~13 mm total length)
      arboreal trap-jaw ant, Odontomachus hastatus (Fabricius) (Hymenoptera:
      Formicidae) in a sandy plain forest on Cardoso Island, off the coast of Southeast
      Brazil. The results showed that O. hastatus nested in root clusters of epiphytic
      bromeliads, most commonly Vriesea procera (70% of nest plants). Mature O.
      hastatus colonies include one to several queens and about 500 workers. Foraging
      by O. hastatus is primarily nocturnal year-round, with increased foraging
      activity during the wet/warm season. The foragers hunt singly in the trees,
      preying on a variety of canopy-dwelling arthropods, with flies, moths, ants, and
      spiders accounting for > 60% of the prey captured. Although predators often have
      impacts on prey populations, the ecological importance of O. hastatus remains to
      be studied.

PMID- 22957687
TI  - Endothelial cell-selective adhesion molecule in diabetic nephropathy.
AB  - BACKGROUND: Endothelial cell-selective adhesion molecule (ESAM) contributes to
      the integrity of tight junctions and modulates endothelial function. ESAM has
      been linked to experimental diabetic nephropathy; its soluble fraction is related
      to atherosclerosis in humans. In this cross-sectional observational study, we
      describe for the first time serum ESAM in type 2 diabetic patients with different
      stages of chronic kidney disease (CKD) and its relationship to vascular
      endothelial growth factor-A (VEGF-A). Materials and methods  We included diabetic
      patients with different stages of CKD and controls. History, laboratory
      evaluation, serum ESAM and VEGF-A and urinary albumin/creatinine ratio were
      obtained. RESULTS: Endothelial cell-selective adhesion molecule was higher in non
      CKD diabetic patients 13.80 (6.15-18.70) ng/mL (n=45) than controls 7.30 (4.60
      9.40) ng/mL (n=48), P=0.001. VEGF-A had a similar pattern: 71.3 (54.75-120.70)
      vs. 43.20 (30.1-65.90) pg/mL, P<0.0001. ESAM was 10.4 (5.6-17.4) ng/mL in
      predialysis CKD patients (n=59) and 22.35 (8.55-29.95) ng/mL in dialysis patients
      (n=36), P<0.001. Patients with glomerular filtration rate (GFR)<15 mL/min had the
      highest ESAM (P=0.003). ESAM was similar in normoalbuminuric, microalbuminuric
      and proteinuric patients. ESAM was directly correlated with the duration of
      diabetes (r(2)=0.048, P=0.009), C-reactive protein (r(2)=0.028, P=0.05), VEGF-A
      (r(2)=0.040, P=0.01) and inversely with HbA1C (r(2)=0.036, P=0.03), haemoglobin
      (r(2)=0.062, P=0.005) and albumin (r(2)=0.0.40, P=0.026). In multiple regression
      diabetes duration, HbA1C and VEGF-A were significant predictors of ESAM. In
      controls, ESAM was inversely related to VEGF (r(2)=037, P=0.01). CONCLUSION:
      Endothelial cell-selective adhesion molecule and VEGF-A are higher in patients
      with diabetes than in controls. The highest ESAM is found in dialysis patients.
      ESAM correlates with diabetes duration and control, inflammation and VEGF-A in
      patients with diabetes, but not in controls.

PMID- 22957688
TI  - Aggregation in a high-mobility n-type low-bandgap copolymer with implications on
      semicrystalline morphology.
AB  - We explore the photophysics of P(NDI2OD-T2), a high-mobility and air-stable n
      type donor/acceptor polymer. Detailed steady-state UV-vis and photoluminescence
      (PL) measurements on solutions of P(NDI2OD-T2) reveal distinct signatures of
      aggregation. By performing quantum chemical calculations, we can assign these
      spectral features to unaggregated and stacked polymer chains. NMR measurements
      independently confirm the aggregation phenomena of P(NDI2OD-T2) in solution. The
      detailed analysis of the optical spectra shows that aggregation is a two-step
      process with different types of aggregates, which we confirm by time-dependent PL
      measurements. Analytical ultracentrifugation measurements suggest that
      aggregation takes place within the single polymer chain upon coiling. By
      transferring these results to thin P(NDI2OD-T2) films, we can conclude that film
      formation is mainly governed by the chain collapse, leading in general to a high
      aggregate content of ~45%. This process also inhibits the formation of amorphous
      and disordered P(NDI2OD-T2) films.

PMID- 22957689
TI  - Regulatory T cells and other lymphocyte subpopulations in patients with melanoma
      developing interferon-induced thyroiditis during high-dose interferon-alpha2b
      treatment.
AB  - CONTEXT: One of the side effects of interferon-alpha therapy is interferon
      induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma
      patients remains to be defined. OBJECTIVE: Our objective was to assess different
      peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in
      melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30
      melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-alpha2b)
      treatment, those who developed IIT (IIT patients) were selected and compared with
      patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral
      blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT),
      end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT).
      RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five
      destructive thyroiditis. An increase in Tregs was observed in both melanoma
      groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations
      and Bcl2 expression on B cells was also observed in both groups. However, no
      changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) gammadelta(+)
      , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ),
      natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT
      was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co
      MM (P = 0.012) and Co-H (P = 0.004), a higher iNKT percentage than Co-MM (P =
      0.011), a higher transitional B cells percentage than Co-H (P = 0.015), a lower
      CD3(+) percentage than Co-H (P = 0.001) and a lower Bcl2 expression on B cells
      than Co-H (P < 0.001). CONCLUSIONS: Our results point to the immunomodulatory
      effects of IFN-alpha on different lymphocyte subpopulations and a possible role
      of Tregs in melanoma patients who developed IIT.

PMID- 22957690
TI  - Synthetic and structural exploration of
      [2(4)]tetrathiacalix[2]arene[2]pyrimidines.
AB  - A novel class of two atom bridged metacyclophanes
      [2(4)]thiacalix[2]arene[2]pyrimidines-has been synthesized via a straightforward
      S(N)Ar reaction. The conformational properties and intra-annular dimensions of
      the [2(4)]thiacalix[2]arene[2]pyrimidines were evaluated by X-ray structure
      analysis and compared with known homothia- and thiacalixarenes. Post
      macrocyclization oxidation of the bridging sulfur moieties resulted in a
      [2(4)]sulfonylcalix[2]arene[2]pyrimidine, which gave access to an unexplored
      cavity size among sulfonylcalixarenes.

PMID- 22957691
TI  - The parasite-host interface in the zonetail butterfly ray, Gymnura zonura
      (Bleeker), infected with Hexacanalis folifer (Cestoda: Lecanicephalidea).
AB  - A wild-caught specimen of the zonetail butterfly ray, Gymnura zonura (Bleeker),
      harboured numerous specimens of Hexacanalis folifer Cielocha & Jensen, 2011
      (Systematic Parasitology, 79, 1-16; Cestoda: Lecanicephalidea) within its spiral
      intestine. The cestodes were primarily attached in single rows along the base of
      mucosal folds, each associated with a nodular mucosal thickening.
      Microscopically, the scolex was embedded within the submucosa and muscularis; the
      attachment sites were marked by ulceration and necro-proliferative inflammation
      demarcating the parasite from normal host tissues. Physical attachment of the
      cestode was restricted to the anterior portion of its scolex where presumed
      tegumental secretions from the apical organ contributed to a cementing
      intermediate layer blending with necrotic host cells. The presence of tegumental
      differentiation between the apical organ and the scolex proper, associated with
      presumed different roles in attachment, correlated with ultrastructural
      observations of the surface modifications on the scolex. Despite the locally
      severe pathological change, insignificant morbidity owing to this particular host
      parasite relationship is suggested.

PMID- 22957692
TI  - Protective effect of CCR5-Delta32 against HIV infection by the heterosexual mode
      of transmission in a Polish population.
AB  - Effects of chemokine receptor alleles (CCR5-Delta32 and CCR2-64I) on
      susceptibility to human immunodeficiency virus (HIV) infection were studied in a
      Polish population. The CCR5 and CCR2 genotypes were determined for 311 healthy,
      HIV-negative individuals (control group), 121 exposed to HIV infection but
      uninfected (EU group), and 470 HIV-positive patients. The frequency of the
      alleles in the control group was calculated as 0.12 for both CCR5-Delta32 and
      CCR2-64I. The logistic regression method was used to analyze the effects of the
      described factors. A protective effect was observed for the CCR5-Delta32 allele
      but only in the case of heterosexual exposure. Prevalence of the CCR5-Delta32/+
      genotype in HIV(+) patients infected via the heterosexual route (n=61; 8.2%) was
      much lower than in the control group (n=311; 21.5%); in the heterosexually
      exposed uninfected group it was slightly higher (n=28; 25%). This suggested that
      in this mode of infection, the native CCR5 expression level was crucial for
      establishment of infection. Individuals with the CCR5-Delta32 allele have more
      than three times less chance of infection in the case of HIV heterosexual
      exposure (odds ratio, 3.37; 95% confidence interval, 1.055-10.76). However, a
      protective effect of the CCR5-Delta32/+ genotype was not observed in the case of
      intravenous drug users (IDUs). The rates of the genotype were similar in HIV
      infected IDU individuals (n=356; 17.7%) and in exposed uninfected patients (n=84;
      15.5%), not significantly different from control group. No effect of the CCR2
      genotype was observed. The analysis revealed that the important factor increasing
      infection risk was, in particular, hepatitis C virus (HCV) infection (odds ratio,
      12.9). Moreover, the effect of HCV infection was found to be age dependent.
      Susceptibility to HIV infection resulting from HCV positivity became weaker (6%
      per year) with increasing age.

PMID- 22957693
TI  - Physicochemical characterization of an aspin (rBm-33) from a filarial parasite
      Brugia malayi against the important human aspartic proteases.
AB  - The aspartic protease inhibitory efficiency of rBm-33, an aspin from a filarial
      parasite Brugia malayi was investigated. rBm-33 was found to be thermostable up
      to 90 degrees C and it forms a stable 'enzyme-product' complex with human pepsin.
      Aspartic protease inhibitory activity was investigated using UV spectroscopy and
      isothermal titration calorimetry. Our results suggest that rBm-33 inhibits the
      activity of important human aspartic proteases that were examined with binding
      constants (Kb) values between 10.23 * 10(3) and 6.52 * 10(3) M(-1). The binding
      reactions were enthalpy driven with DeltaHb values between -50.99 and -46.07 kJ
      mol(-1). From kinetic studies, pepsin inhibition by rBm-33 was found to be linear
      competitive with an inhibition constant (Ki) of 2.5 (+/-0.8) nM. Because of the
      inhibitory efficacy of Bm-33 against important human aspartic proteases which
      play a vital role in immune-regulation along with other functions, Bm-33 can be
      projected as a drug target for the filariasis.

PMID- 22957694
TI  - Frequency, time course, and possible causes of right ventricular systolic
      dysfunction after cardiac transplantation: a single center experience.
AB  - BACKGROUND: The frequency and causes of right ventricular (RV) systolic
      dysfunction early after cardiac transplantation are not well defined. METHODS: We
      investigated the prevalence and causes of RV dysfunction in 27 heart transplant
      recipients, as measured by lateral tricuspid annular plane excursion (TAPSE) and
      fractional area change (FAC) at a mean of 15 +/- 11 days after transplant. Tissue
      Doppler imaging was used to assess systolic time velocity integral (TVI) of the
      RV basal free wall. A subset of 22 patients had follow-up TAPSE measurement at
      406 +/- 121 days. RESULTS: RV systolic dysfunction, defined as TAPSE > 2 standard
      deviation (SD) below values in a control group, was present in 100% (27/27) of
      patients (P < 0.05). FAC was also significantly lower in patients compared with
      controls (P < 0.0001). TVI confirmed the presence of RV dysfunction in all 16
      patients with both TAPSE and TVI (P < 0.05). Ischemic time (P = 0.017) and
      posttransplant tricuspid regurgitation (P = 0.024) were independent predictors of
      early RV dysfunction (r = 0.753). On follow-up, RV function improved in 15 of 22
      patients but all patients remained with TAPSE > 2 SD below controls. CONCLUSION:
      This study showed that 100% of patients had reduced RV function early after
      transplant. Two thirds of patients had partial recovery of RV function during the
      first year. In all patients, however, RV function remained significantly lower
      than in controls.

PMID- 22957695
TI  - Antitumor platinum(II) complexes containing platinum-based moieties of present
      platinum drugs and furoxan groups as nitric oxide donors: synthesis, DNA
      interaction, and cytotoxicity.
AB  - Six novel platinum(II) complexes 1-6 bearing different furoxan moieties as nitric
      oxide (NO) donors have been designed, synthesized, and characterized by elemental
      analysis and (1)H NMR, IR, and ESI-MS spectroscopy. The furoxan groups were
      introduced to the platinum complexes to release NO, which may take synergic
      action with the platinum-based moieties on the tumor cells. It was found that all
      compounds exhibited considerable cytotoxicity against human HCT-116 and SGC-7901
      cell lines via DNA binding together with NO-releasing features, especially for
      compound 3. This finding is in accordance with the previous reports that NO
      hybrids show higher cytotoxicity against colon cancer cell lines compared with
      their parent compounds.

PMID- 22957696
TI  - Cutaneous haemorrhage induced by minimal trauma as a sign of light chain
      associated amyloidosis.

PMID- 22957697
TI  - Defective valyl-tRNA synthetase hampers the mitochondrial respiratory chain in
      Neurospora crassa.
AB  - Respiratory chain deficiency can result from alterations in mitochondrial and/or
      cytosolic protein synthesis due to the dual genetic origin of mitochondrial
      oxidative phosphorylation. In the present paper we report a point mutation
      (D750G) in the bifunctional VARS (valyl-tRNA synthetase) of the fungus Neurospora
      crassa, associated with a temperature-sensitive phenotype. Analysis of the mutant
      strain revealed decreased steady-state levels of VARS and a clear reduction in
      the rate of mitochondrial protein synthesis. We observed a robust induction of
      the mitochondrial alternative oxidase with a concomitant decrease in the
      canonical respiratory pathway, namely in cytochrome b and aa3 content.
      Furthermore, the mutant strain accumulates the peripheral arm of complex I and
      depicts decreased levels of complexes III and IV, consistent with severe
      impairment of the mitochondrial respiratory chain. The phenotypic alterations of
      the mutant strain are observed at the permissive growth temperature and
      exacerbated upon increase of the temperature. Surprisingly, glucose-6-phosphate
      dehydrogenase activities were similar in the wild-type and mutant strains,
      whereas mitochondrial activities for succinate dehydrogenase and alternative NADH
      dehydrogenases were increased in the mutant strain, suggesting that the VARSD-G
      mutation does not affect overall cytosolic protein synthesis. Expression of the
      wild-type vars gene rescues all of the mutant phenotypes, indicating that the
      VARSD-G mutation is a loss-of-function mutation that results in a combined
      respiratory chain deficiency.

PMID- 22957698
TI  - Colloid adhesive parameters for chemically heterogeneous porous media.
AB  - A simple modeling approach was developed to calculate colloid adhesive parameters
      for chemically heterogeneous porous media. The area of the zone of electrostatic
      influence between a colloid and solid-water interface (A(z)) was discretized into
      a number of equally sized grid cells to capture chemical heterogeneity within
      this region. These cells were divided into fractions having specific zeta
      potentials (e.g., negative or positive values). Mean colloid adhesive parameters
      such as the zeta potential, the minimum and maximum in the interaction energy,
      the colloid sticking efficiency (alpha), and the fraction of the solid surface
      area that contributes to colloid immobilization (S(f)) were calculated for
      possible charge realizations within A(z). The probability of a given charge
      realization in A(z) was calculated using a binomial mass distribution.
      Probability density functions (PDFs) for the colloid adhesive parameters on the
      heterogeneous surface were subsequently calculated at the representative
      elementary area (REA) scale for a porous medium. This approach was applied
      separately to the solid-water interface (SWI) and the colloid, or jointly to both
      the SWI and colloid. To validate the developed model, the mean and standard
      deviation of the interaction energy distribution on a chemically heterogeneous
      SWI were calculated and demonstrated to be consistent with published Monte Carlo
      simulation output using the computationally intensive grid surface integration
      technique. Our model results show that the PDFs of colloid adhesive parameters at
      the REA scale were sensitive to the size of the colloid and the heterogeneity,
      the charge and number of grid cells, and the ionic strength.

PMID- 22957701
TI  - A comprehensive study on long-term injury to nigral dopaminergic neurons
      following intracerebroventricular injection of lipopolysaccharide in rats.
AB  - Parkinson's disease (PD) is characterized by selective and progressive
      degeneration of dopaminergic neurons in the substantia nigra (SN).
      Lipopolysaccharide (LPS) can induce chronic inflammation and has been widely used
      to study the pathogenesis of PD. In this study, a single intracerebroventricular
      injection of LPS was used to induce neurotoxic effects on dopaminergic neurons in
      Sprague-Dawley rats. The long-term neurotoxic effects of LPS were evaluated at
      different time points. Microglia were activated in the hippocampus and striatum
      at 4 weeks, and in the SN at 24 weeks. Astrocytes were activated in the
      hippocampus and nigrostriatal system at 2 and 24 weeks. The expression of brain
      derived neurotrophic factor in the SN increased at 4 weeks and decreased after 12
      weeks, and tyrosine hydroxylase-positive neurons in the SN were shown to have an
      atrophic appearance, with cell loss evident after 24 weeks. Phospho-alpha
      synuclein expression, a reflection of parkinsonian pathogenesis, increased at 12
      weeks, and peaked at 24 weeks. Abnormal motor behavior appeared at 16 weeks and
      lasted up to 48 weeks. These results indicate that microglia are activated for
      several months after a single, low dose injection of LPS, which eventually
      results in progressive and selective damage to dopaminergic neurons in the SN.

PMID- 22957702
TI  - Novel seed coat lignins in the Cactaceae: structure, distribution and
      implications for the evolution of lignin diversity.
AB  - We have recently described a hitherto unsuspected catechyl lignin polymer (C
      lignin) in the seed coats of Vanilla orchid and in cacti of one genus, Melocactus
      (Chen et al., Proc. Natl. Acad. Sci. USA. 2012, 109, 1772-1777.). We have now
      determined the lignin types in the seed coats of 130 different cactus species.
      Lignin in the vegetative tissues of cacti is of the normal guaiacyl/syringyl
      (G/S) type, but members of most genera within the subfamily Cactoidae possess
      seed coat lignin of the novel C-type only, which we show is a homopolymer formed
      by endwise beta-O-4-coupling of caffeyl alcohol monomers onto the growing polymer
      resulting in benzodioxane units. However, the species examined within the genera
      Coryphantha, Cumarinia, Escobaria and Mammillaria (Cactoideae) mostly had normal
      G/S lignin in their seeds, as did all six species in the subfamily Opuntioidae
      that were examined. Seed coat lignin composition is still evolving in the
      Cactaceae, as seeds of one Mammillaria species (M. lasiacantha) possess only C
      lignin, three Escobaria species (E. dasyacantha, E. lloydii and E. zilziana)
      contain an unusual lignin composed of 5-hydroxyguaiacyl units, the first report
      of such a polymer that occurs naturally in plants, and seeds of some species
      contain no lignin at all. We discuss the implications of these findings for the
      mechanisms that underlie the biosynthesis of these newly discovered lignin types.

PMID- 22957700
TI  - Heme binding properties of glyceraldehyde-3-phosphate dehydrogenase.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme that also
      functions in transcriptional regulation, oxidative stress, vesicular trafficking,
      and apoptosis. Because GAPDH is required for the insertion of cellular heme into
      inducible nitric oxide synthase [Chakravarti, R., et al. (2010) Proc. Natl. Acad.
      Sci. U.S.A. 107, 18004-18009], we extensively characterized the heme binding
      properties of GAPDH. Substoichiometric amounts of ferric heme bound to GAPDH (one
      heme per GAPDH tetramer) to form a low-spin complex with UV-visible maxima at
      362, 418, and 537 nm and when reduced to ferrous gave maxima at 424, 527, and 559
      nm. Ferric heme association and dissociation rate constants at 10  degrees C were
      as follows: k(on) = 17800 M(-1) s(-1), k(off1) = 7.0 * 10(-3) s(-1), and k(off2)
      = 3.3 * 10(-4) s(-1) (giving approximate affinities of 19-390 nM). Ferrous heme
      bound more poorly to GAPDH and dissociated with a k(off) of 4.2 * 10(-3) s(-1).
      Magnetic circular dichroism, resonance Raman, and electron paramagnetic resonance
      spectroscopic data on the ferric, ferrous, and ferrous-CO complexes of GAPDH
      showed that the heme is bis-ligated with His as the proximal ligand. The distal
      ligand in the ferric complex was not displaced by CN(-) or N(3)(-) but in the
      ferrous complex could be displaced by CO at a rate of 1.75 s(-1) (for >0.2 mM
      CO). Studies with heme analogues revealed selectivity toward the coordinating
      metal and porphyrin ring structure. The GAPDH-heme complex was isolated from
      bacteria induced to express rabbit GAPDH in the presence of delta-aminolevulinic
      acid. Our finding of heme binding to GAPDH expands the protein's potential roles.
      The strength, selectivity, reversibility, and redox sensitivity of heme binding
      to GAPDH are consistent with it performing heme sensing or heme chaperone-like
      functions in cells.

PMID- 22957703
TI  - Methaemoglobinaemia caused by the ingestion of poisoned meat in a Romanian
      community in Italy.

PMID- 22957704
TI  - Development of natural tolerance and induced desensitization in cow's milk
      allergy.
AB  - Cow's milk allergy (CMA) affects 2-3% of infants. It resolves in the great
      majority spontaneously during childhood. CMA encompasses a spectrum of clinical
      and immunologic characteristics. Non-IgE-mediated allergy typically resolves
      earlier than IgE-mediated allergy. The most documented prognostic characteristic
      is that intense-specific IgE response predicts persistence of CMA. Low serum
      levels of cow's milk (CM)-specific IgG4 are also associated with persistent CMA.
      Natural development of tolerance involves an immunologic shift where Th2
      responses diminish, and Th1 as well as T regulatory cell responses strengthen.
      Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA,
      levels increase in serum. Specific oral immunotherapy (OIT) with CM induces
      desensitization in most cases where spontaneous recovery has not yet occurred.
      Data on long-term tolerance induction are still scarce. According to current
      research data, the immunologic changes induced by OIT resemble those seen during
      natural development of tolerance.

PMID- 22957706
TI  - Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese
      children with onset of diabetes before 5 years of age.
AB  - BACKGROUND: The etiology of type 1 diabetes (T1D) is heterogeneous and is
      according to presence or absence of pancreatic autoantibodies divided into two
      subtypes: type 1A (autoimmune-mediated) and type 1B (non-autoimmune-mediated).
      Although several genes have been linked to type 1A diabetes, the genetic cause of
      type 1B diabetes in Japanese individuals is far from understood. OBJECTIVE: The
      aim of this study was to test for monogenic forms of diabetes in auto antibody
      negative Japanese children with T1D. METHODS: Thirty four (19 males and 15
      female) unrelated Japanese children with glutamate decarboxylase (GAD) 65
      antibodies and/or IA-2A-negative T1D and diabetes diagnosed at < 5 yr of age were
      recruited from 17 unrelated hospitals participating in the Japanese Study Group
      of Insulin Therapy for children and adolescent diabetes (JSGIT). We screened the
      INS gene and the KCNJ11 gene which encode the ATP-sensitive potassium cannel by
      direct sequencing in 34 Japanese children with T1D. RESULTS: We identified three
      novel (C31Y, C96R, and C109F) mutations and one previously reported mutation
      (R89C) in the INS gene in five children, in addition to one mutation in the
      KCNJ11 gene (H46R) in one child. These mutations are most likely pathogenic and
      therefore the cause of diabetes in carriers. CONCLUSION: Our results suggest that
      monogenic forms of diabetes, particularly INS gene mutations, can be detected in
      Japanese patients classified with type 1B. Mutation screening, at least of the
      INS gene, is recommended for Japanese patients diagnosed as autoantibody negative
      at <5 yr of age.

PMID- 22957707
TI  - Aquatic insects of New York salt marsh associated with mosquito larval habitat
      and their potential utility as bioindicators.
AB  - The aquatic insect fauna of salt marshes is poorly characterized, with the
      possible exception of biting Diptera. Aquatic insects play a vital role in salt
      marsh ecology, and have great potential importance as biological indicators for
      assessing marsh health. In addition, they may be impacted by measures to control
      mosquitoes such as changes to the marsh habitat, altered hydrology, or the
      application of pesticides. Given these concerns, the goals of this study were to
      conduct the first taxonomic survey of salt marsh aquatic insects on Long Island,
      New York, USA and to evaluate their utility for non-target pesticide impacts and
      environmental biomonitoring. A total of 18 species from 11 families and five
      orders were collected repeatedly during the five month study period. Diptera was
      the most diverse order with nine species from four families, followed by
      Coleoptera with four species from two families, Heteroptera with three species
      from three families, then Odonata and the hexapod Collembola with one species
      each. Water boatmen, Trichocorixa verticalis Fieber (Heteroptera: Corixidae) and
      a shore fly, Ephydra subopaca Loew (Diptera: Ephydridae), were the two most
      commonly encountered species. An additional six species; Anurida maritima Guerin
      Meneville (Collembola: Neanuridae), Mesovelia mulsanti White (Heteroptera:
      Mesovelidae), Enochrus hamiltoni Horn (Coleoptera: Hydrophilidae), Tropisternus
      quadristriatus Horn (Coleoptera: Hydrophilidae), Dasyhelea pseudocincta Waugh and
      Wirth (Diptera: Ceratopogonidae), and Brachydeutera argentata Walker (Diptera:
      Ephydridae), were found regularly. Together with the less common Erythrodiplax
      berenice Drury (Odonata: Libellulidae), these nine species were identified as the
      most suitable candidates for pesticide and environmental impact monitoring due to
      abundance, position in the food chain, and extended seasonal occurrence. This
      study represents a first step towards developing an insect-based index of
      biological integrity for salt marsh health assessment.

PMID- 22957708
TI  - Diode laser thermotherapy for conjunctival vascular malformations.

PMID- 22957709
TI  - A general strategy to superstructured networks and nested self-similar networks
      of bismuth compounds.
AB  - We have reported the synthesis of superstructured nanonetworks of BiOCl and
      nested nanonetworks of Bi(2)S(3) in a series of lattice-directed topotactic
      transformations [C. F. Guo et al. J. Am. Chem. Soc. 2011, 138, 8211-8215]. Here
      we extend the transformations to a much broader system including ordered nanowall
      networks of BiOCl, BiOBr, Bi(2)O(2)CO(3), beta-Bi(2)O(3), and Bi(2)S(3), as well
      as nested self-similar networks of Bi(2)S(3) and amorphous BiO(x). We suggest
      even more superstructured networks and nested self-similar networks of bismuth
      compounds with a lattice parameter of ~2(n/2) * 3.9 A (n = 0, 1, 2, 3, 4), might
      also be obtained. The superstructured networks and nested networks are novel
      architectures that may find applications in electronic devices, sensors, filters,
      and photocatalysts.

PMID- 22957710
TI  - The transferrin-iron import system from pathogenic Neisseria species.
AB  - Two pathogenic species within the genus Neisseria cause the diseases gonorrhoea
      and meningitis. While vaccines are available to protect against four N.
      meningitidis serogroups, there is currently no commercial vaccine to protect
      against serogroup B or against N. gonorrhoeae. Moreover, the available vaccines
      have significant limitations and with antibiotic resistance becoming an alarming
      issue, the search for effective vaccine targets to elicit long-lasting protection
      against Neisseria species is becoming more urgent. One strategy for vaccine
      development has targeted the neisserial iron import systems. Without iron, the
      Neisseriae cannot survive and, therefore, these iron import systems tend to be
      relatively well conserved and are promising vaccine targets, having the potential
      to offer broad protection against both gonococcal and meningococcal infections.
      These efforts have been boosted by recent reports of the crystal structures of
      the neisserial receptor proteins TbpA and TbpB, each solved in complex with human
      transferrin, an iron binding protein normally responsible for delivering iron to
      human cells. Here, we review the recent structural reports and put them into
      perspective with available functional studies in order to derive the mechanism(s)
      for how the pathogenic Neisseriae are able to hijack human iron transport systems
      for their own survival and pathogenesis.

PMID- 22957711
TI  - Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and
      staining in gingivitis patients: a systematic review.
AB  - AIM: To systematically evaluate the efficacy of chlorhexidine (CHX) mouthrinses
      on plaque, gingival inflammation and staining in gingivitis patients. MATERIAL &
      METHODS: Medline, EMBASE and Cochrane Central Register of Controlled Trials were
      searched through April 2011. Randomized controlled clinical trials comparing CHX
      to placebo/control mouthrinses or oral hygiene (OH) >= 4 weeks were included.
      RESULTS: Among 1355 titles, 30 publications fulfilled the selection criteria.
      Meta-analysis (MA) showed significant weighted mean differences (WMD) favouring
      CHX. This was -0.39 [95% CI: -0.70; -0.08] for the Plaque Index Silness & Loe, 
      0.67 [95% CI: -0.82; -0.52] for the Plaque-Index Quigley & Hein (PIQH), -0.32
      [95% CI: -0.42; -0.23] for the Gingival Index (GI), -0.08 [95% CI: -0.10; -0.05]
      for the bleeding aspect of the GI, -0.21 [95% CI: -0.37; -0.04] for the Papillary
      BIeeding Index, -0.16 [95% CI: -0.26; -0.07] for Bleeding on Marginal Probing and
      0.91 [95% CI: 0.12;1.70] for the Lobene Stain Index. MA of studies with a low
      risk of author-estimated bias showed a WMD of -0.68 [95% CI: -0.85; -0.51] for
      the PIQH and -0.24 [95% CI: -0.29; -0.20] for the GI in favour of CHX. Relative
      to control, the reduction with CHX for plaque was 33% and for gingivitis 26%. CHX
      rinsing groups demonstrated significantly more staining. CONCLUSIONS: In
      gingivitis patients, CHX mouthrinses together with OH versus placebo- or control
      mouthrinse provide significant reductions in plaque and gingivitis scores, but a
      significant increase in staining score.

PMID- 22957712
TI  - Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial
      growth factor receptor 2, in patients with advanced solid tumors.
AB  - Targeting of tumor angiogenesis with vaccines is a potentially valuable approach
      to cancer treatment. Elpamotide is an immunogenic peptide derived from vascular
      endothelial growth factor receptor 2, which is expressed at a high level in
      vascular endothelial cells. We have now carried out a phase I study to evaluate
      safety, the maximum tolerated dose, and potential pharmacodynamic biomarkers for
      this vaccine. Ten HLA-A*24:02-positive patients with advanced refractory solid
      tumors received elpamotide s.c. at dose levels of 0.5, 1.0, or 2.0 mg once a week
      on a 28-day cycle. Five patients experienced an injection site reaction of grade
      1 and 2, which was the most frequent adverse event. In the 1.0 mg cohort, one
      patient experienced proteinuria of grade 1 and another patient developed both
      hypertension and proteinuria of grade 1. No adverse events of grade 3 or higher
      were observed, and the maximum tolerated dose was therefore not achieved. The
      serum concentration of soluble vascular endothelial growth factor receptor 2
      decreased significantly after elpamotide vaccination. Microarray analysis of gene
      expression in PBMCs indicated that several pathways related to T cell function
      and angiogenesis were affected by elpamotide vaccination, supporting the notion
      that this peptide induces an immune response that targets angiogenesis in the
      clinical setting. In conclusion, elpamotide is well tolerated and our biomarker
      analysis indicates that this anti-angiogenic vaccine is biologically active.
      Clinical trial registration no. UMIN000008336.

PMID- 22957713
TI  - The effects of bestatin on humoral response to sheep erythrocytes in non-treated
      and cyclophosphamide-immunocompromised mice.
AB  - The effects of bestatin on humoral immune response to sheep erythrocytes (SRBC)
      and restoration of the response impaired by a single cyclophosphamide dose (350
      mg/kg) were tested on mice. Bestatin (at doses of 10, 1, and 0.1 mg/kg) was
      administered intraperitoneally (i.p.) 5 or 10 times. The pharmacological
      immunosuppression was induced by a single i.p. injection of cyclophosphamide (350
      mg/kg) administered 24 h before the first bestatin dose. The mice were immunized
      i.p. with SRBC 24 h after the last dose of bestatin. It was found that multiple
      administration of bestatin at all three doses potentiated the humoral response to
      SRBC in non-treated mice, resulting in an increased number of plaque-forming
      cells (PFC) and 2-mercaptoethanol (2-ME)-resistant anti-SRBC antibodies. However,
      five times administration of bestatin at the doses under investigation caused
      further decreases in total anti-SRBC hemagglutinins. A single injection of
      cyclophosphamide (350 mg/kg) suppressed humoral response of mice to the antigen.
      Administration of bestatin after pharmacological immunosuppression partially
      prevented the suppressive action of cyclophosphamide in the in vivo model of the
      humoral immune response to SRBC. The protective action of bestatin was both dose-
      and schedule-dependent. Ten times' exposure to a bestatin dose of 0.1 mg/kg after
      a high cyclophosphamide dose partially reduced the suppressive effect of this
      drug on humoral response of SRBC-immunized mice, increasing PFC on days 4 and 7
      after immunization, which coincided with restored ability of the lymphocytes to
      produce the 2-ME-resistant hemagglutinins on day 7 and the total anti-SRBC
      hemagglutinins on day 14 after priming.

PMID- 22957714
TI  - Regio- and diastereoselective nickel-catalyzed allylation of aromatic aldehydes
      with alpha-halo-beta,beta-difluoropropene derivatives.
AB  - A one-pot nickel-catalyzed allylation of aromatic aldehydes with alpha-halo
      beta,beta-difluoropropene-containing compounds promoted by ZnEt(2) under mild
      conditions was described. The reaction displays moderate to good regio- and
      diastereoselectivity, tolerates a wide range of functional groups, and provides
      an efficient method for the synthesis of gamma-fluorinated homoallylic alcohols.

PMID- 22957715
TI  - In vivo effects of a single intra-articular injection of 2% lidocaine or 0.5%
      bupivacaine on articular cartilage of normal horses.
AB  - OBJECTIVE: To assess the effects of an intra-articular (IA) lidocaine or
      bupivacaine injection on synovial fluid (SF) biomarkers of cartilage metabolism.
      STUDY DESIGN: Experimental. ANIMALS: Horses (n = 6). METHODS: The study had 2
      components, each with an identical design: the first arm assessed the effects of
      bupivacaine (0.5%) IA in the intercarpal joints and, after a 2-week washout
      period, the second was conducted to evaluate the effects of IA lidocaine (2%) in
      the tarsocrural joints. The mares were randomly assigned to receive the test
      local anesthetic in the target joint or the placebo (0.9% NaCl) in the
      contralateral joint. After a 2-week washout period, treatments were reversed,
      yielding 6 joints for each treatment. SF samples were collected for measurement
      of biomarkers of cartilage metabolism. RESULTS: IA bupivacaine or lidocaine
      induced a significant increase in both markers of cartilage matrix synthesis
      (CS846-aggrecan and CPII-type II collagen) suggesting an anabolic effect.
      Bupivacaine also resulted in an unanticipated decrease in both collagen
      degradation markers (C2C and C1,2C). CONCLUSIONS: These results reveal an
      anabolic effect of single IA injections of local anesthetics on cartilage
      metabolism. Although collagen degradation biomarker results were not increased,
      it is possible that the anabolic response is because of an undetected cartilage
      insult, and requires further investigation.

PMID- 22957716
TI  - Antimicrobial susceptibility pattern of Flavobacterium columnare isolates
      collected worldwide from 17 fish species.
AB  - Flavobacterium columnare is the causative agent of columnaris disease in diverse
      fish species worldwide. Although columnaris is an important disease, the
      antimicrobial susceptibility pattern of F. columnare is not well studied. Thus,
      the purpose of this study was to test the in vitro antimicrobial susceptibility
      of 97 F. columnare isolates collected worldwide between 1987 and 2011 from 17
      fish species. The broth microdilution technique was utilized for reliable testing
      of these fastidious organisms. None of the isolates displayed acquired resistance
      to florfenicol, gentamicin, ormetoprim-sulfadimethoxine and trimethoprim
      sulfamethoxazole. Acquired resistance to chloramphenicol was detected in 1%, to
      nitrofuran in 5%, to oxytetracycline in 11% and to enrofloxacin, flumequine and
      oxolinic acid in 10%, 16% and 16% of the isolates, respectively, as reflected by
      a bimodal or trimodal distribution of their minimum inhibitory concentrations
      (MICs). One isolate showed acquired resistance towards several antimicrobial
      agents including erythromycin. Another isolate revealed acquired resistance
      towards - amongst others - ampicillin. The isolates displaying acquired
      resistance originated from ornamental fish species or Vietnamese catfish, except
      for two isolates coming from wild channel catfish in which acquired resistance
      was encountered towards oxytetracycline only. Fifty per cent of the resistant
      isolates from ornamental fish were shown to have acquired resistance against
      three classes of antimicrobial agents, assigning these isolates as multiple
      resistant. These data might indicate less prudent use of antimicrobials
      especially in ornamental fish species.

PMID- 22957717
TI  - Primary lateral sclerosis: predicting functional outcome.
AB  - Our objective was to investigate functional outcome in primary lateral sclerosis
      (PLS). We followed a group of 24 patients with PLS. Clinical (ALSFRS),
      respiratory, and neurophysiological (electromyography and transcranial magnetic
      stimulation) evaluations were performed at entry and regularly over the follow-up
      period. The time taken for a greater than 10% decrease in ALSFRS compared to the
      first assessment was defined as the dichotomous outcome; prognostic factors were
      evaluated using the Cox proportional hazard model. Results demonstrated that the
      median age at symptom onset was 54 years (range 28-75 years). In 46% symptoms
      began in the lower limbs, in 21% in the upper limbs and in 33% in bulbar muscles.
      The median symptom duration at first visit was 3.1 years (range 0.9-11.7 years).
      At last follow-up the median disease duration was 9.9 years (range 4.2-17.6
      years). The median follow-up time was 4.6 years (range 2.1-11 years). We excluded
      from final analysis three patients with positive family history. Older age at
      onset (p = 0.019) was related to more rapid functional impairment; gender, forced
      vital capacity, region of onset and neurophysiological changes did not predict
      outcome. In conclusion, age is the most critical prognostic factor for functional
      outcome in PLS.

PMID- 22957718
TI  - Pharmacological descriptors related to the binding of Gp120 to CD4 corresponding
      to 60 representative HIV-1 strains.
AB  - The standardization of HIV-1 strains for vaccine tests include the use of viral
      reference panels. We determined a series of pharmacological descriptors
      (molecular surfaces, volumes, electrostatic energies, solvation energies, number
      of atoms, number of hydrogen donors or acceptors and number of rigid bonds) for
      the gp120 CD4-binding sites structures in the unliganded state from a reference
      panel of 60 diverse strains of HIV-1. We identified the descriptors that varied
      significantly between the strains, the outliner strains for each descriptor set
      and the possible correlations between the descriptors. Our results improve the
      knowledge about gp120, its molecular and possible neutralization properties. 

PMID- 22957719
TI  - Synthesis and anti-inflammatory activity of celecoxib like compounds.
AB  - Nine novel 4-[3-(4-Dimethylamino-phenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]
      benzenesulfonamides (2a-i) were synthesized and evaluated for their anti
      inflammatory and antiproliferative activities. These compounds (2a-i) showed
      moderate to strong anti-inflammatory activity in carrageenan rat paw oedema test.
      Compounds 2b, 2d and 2g showing comparable anti-inflammatory activity to that of
      reference drug celecoxib were evaluated for their ulcerogenic and analgesic
      activities. The effect of 2b, 2d and 2g on the content of NO, TNF-alpha and PGE2
      in exudates from rat paw stimulated by carrageenan was also evaluated. The
      compound 2c showed considerable antitumor activities against all 60 human tumor
      cell lines with effective GI50 (MG-MID) value of 3.63 uM. It exhibited maximum
      activity against melanoma (LOX IMVI and SK-MEL-5) cancer cell lines with GI50
      value less than 2 MUM. 

PMID- 22957720
TI  - Synthesis, biological evaluation and docking studies of new pyrrolo[2,3-d]
      pyrimidine derivatives as Src family-selective tyrosine kinase inhibitors.
AB  - In this study, the synthesis and potential enzyme interactions of new Pyrrolo[2,3
      d]pyrimidine derivatives along with their inhibitory activity against SFK enzymes
      such as Fyn, Lyn, Hck, and c-Src were reported. The results indicated that
      compounds were slightly active of tested SFK enzymes in comparison with PP2 for
      Fyn, A-419259 for Lyn and CGP77675 for c-Src. Compound N-((2-amino-4-oxo-4,7
      dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)-4-(3,4-dimethoxyphenyl)butanamide
      (5) was identified as a non-selective slight inhibitor against Fyn, Lyn and c
      Src. However, compounds did not show any inhibitory effects on Hck. Docking
      studies were performed to analyze the binding mode of compounds against SFKs. The
      best interaction was obtained between compound 5 and the active site of Fyn and c
      Src enzymes in comparison with reference compounds PP2 and CGP77675,
      respectively. 

PMID- 22957721
TI  - In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase 1B.
AB  - Protein Tyrosine Phosphatase 1B (PTP1B) is a major negative regulator of insulin
      signaling pathways. Finding selective PTP1B inhibitors from natural sources has
      been widely recognized as a potential drug target for the treatment of diabetes
      mellitus and obesity. In the present study, we evaluated the inhibitory activity
      of cinnamic acid derivatives against PTP1B in vitro. Among 14 cinnamic acid
      derivatives and related compounds, the most potent inhibitor PTP1Bs were o
      hydroxycinnamic acid and p-hydroxycinnamic acid, which had IC50 values of 137.67
      +/- 13.37 and 181.60 +/- 9.34 uM, respectively. The kinetics analysis revealed
      that PTP1B was inhibited by o-hydroxycinnamic acid and p-hydroxycinnamic acid in
      a non-competitive manner. o-Hydroxycinnamic acid (25 MUM) and p-hydroxycinnamic
      acid (25 MUM), in combination with sodium orthovanadate (0.0125 MUM),
      demonstrated a synergistic effect to inhibit PTP1B activity. In conclusion, the
      findings provide a new insight into naturally occurring PTP1B inhibitors that
      could be useful for treatment of diabetes and obesity.

PMID- 22957722
TI  - Design and synthesis of 3-[(7-chloro-1-oxidoquinolin-4-ylamino)alkyl]-1,3
      thiazolidin-4-ones as antimalarial agents.
AB  - A new series of quinoline analogs have been synthesized and found active against
      P. falciparum in vitro and P. yoelli in vivo. Compounds 8, 10 and 11 exhibited
      superior in vitro activity compared to chloroquine. Selected compounds 8, 10 and
      11 exhibited significant suppression of parasitaemia in vivo assay. These analogs
      form a complex with hematin and inhibit the beta-hematin formation, suggesting
      that this class of compounds act on a heme polymerization target. Further this
      study confirms that quinoline ring nitrogen is essential for both transportation
      of the molecule across the membrane as well as for tight binding to hematin. 

PMID- 22957723
TI  - Molecular modelling design, synthesis and cytotoxic evaluation of certain
      substituted 2-(3,4,5-triacetoxybenzoylamino)benzo[d]thiazole and 2
      (galloylamino)benzo[d]thiazole derivatives having potential topoisomerase-I
      inhibitory activity.
AB  - New 2-(3,4,5-triacetoxybenzoylamino)benzothiazoles (4a~5f) and 2
      (galloylamino)benzothiazoles (6a~7f), were designed as topoisomerase-I
      inhibitors. Compare/fit studies between these molecules and the generated
      topoisomerase-I inhibitors hypothesis revealed that 4a~5f have higher fitting
      values than (6a~7f). Also, docking of 4a~7f with the topoisomerase-I enzyme
      prioritized the higher activity of (4a~5f) than (6a~7f). These molecules were
      synthesized and biologically evaluated for their in vitro cytotoxic activity
      against Hela and MCF7 human cancer cell lines in comparison to Camptothecin (topo
      I inhibitor) and doxorubicin (topo-II inhibitors) as reference drugs. Such
      screening revealed that compounds 4d, 4e, 4h, 5b, 5c and 5e have comparable
      higher cytotoxic activity in both cultures than these reference drugs. The
      highest active molecule was 5f that gave 1.5 folds higher cytotoxic activity
      against Hela cell cultures and 1.9 folds higher activity against MCF7 cell lines
      than doxorubicin and 1.6 folds and 2.2 folds higher activity towards the two
      respective cultures than Camptothecin. 

PMID- 22957724
TI  - Synthesis and characterization of metal complexes of heterocyclic sulfonamide as
      carbonic anhydrase inhibitors.
AB  - Three novel metal complexes of N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-4
      benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide which possess strong
      carbonic anhydrase (CA) inhibitory properties have been synthesised. The
      structure of these compounds has been investigated by elemental analysis, FT-IR,
      LC/MS, UV-vis spectrophotometric method and magnetic susceptibility. Human
      carbonic anhydrase isoenzymes hCA-I and hCA-II were purified from erythrocyte
      cells by the affinity chromatography. The inhibitory effects of newly synthesized
      complexes and acetazolamide (AAZ) as a control compound on hydratase and esterase
      activities of these isoenzymes have been studied in vitro by comparing IC(50) and
      K(i) values and it has been found that the newly synthesised complexes behave as
      very powerful inhibitors against hCA-I and hCA-II than parent ligand (1) and than
      AAZ.

PMID- 22957725
TI  - Regioselective acylation of congeners of 3-amino-1H-pyrazolo[3,4-b]quinolines,
      their activity on bacterial serine/threonine protein kinases and in vitro
      antibacterial (including antimycobacterial) activity.
AB  - It was found by virtual screening that 3-amino-1H-pyrazolo[3,4-b]quinolines could
      have wide protein kinase inhibitory activity. Amides of titled amines and
      thioureas were synthesized regioselectively. 3-Amino-7-methoxy-1H-pyrazolo[3,4
      b]quinoline demonstrated in vitro significant inhibitory activity on bacterial
      serine/threonine protein kinases (inhibition of resistance to kanamycin in
      Streptomyces lividans regulated by protein kinases). The studies of Structure
      Activity Relationship (SAR) showed that the substitution of the NH2 group and 1
      NH of pyrazole ring or aromatic ring at the position 6 decreased or removed
      inhibitory activity. 

PMID- 22957726
TI  - Progressive outer retinal necrosis presenting as cherry red spot.
AB  - PURPOSE: To report a case of progressive outer retinal necrosis (PORN) presenting
      as a cherry red spot. METHODS: Case report. RESULTS: A 53-year-old woman with
      recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis
      developed rapid sequential vision loss in both eyes over 2 months. Her exam
      showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary
      changes, consistent with PORN. Due to her late presentation and the rapid
      progression of her condition, she quickly developed end-stage vision loss in both
      eyes. CONCLUSIONS: PORN should be considered within the differential diagnosis of
      a "cherry red spot." Immune-deficient patients with a history of herpetic
      infection who present with visual loss warrant prompt ophthalmological
      evaluation.

PMID- 22957727
TI  - Atorvastatin treatment improves myocardial and peripheral blood flow in familial
      hypercholesterolemia subjects without evidence of coronary atherosclerosis.
AB  - BACKGROUND: Hypercholesterolemia induces early microcirculatory functional and
      structural alterations that are reversible by cholesterol reduction. Real time
      myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the
      effects of hyperlipidemia on peripheral and central blood flow reserve. This
      study investigated the effects of lipid-lowering therapy on coronary and
      peripheral artery circulation in patients with familial hypercholesterolemia
      (FH). METHODS: RTMCE and vascular ultrasound were performed in 10 healthy
      volunteers (validation group) at baseline and after 12-week clinical observation,
      and in 16 age- and sex-matched FH patients without obstructive coronary artery
      disease (CAD) by computed tomography angiography at baseline and after 12-week
      atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were
      obtained at rest and during adenosine infusion. RESULTS: In validation group,
      there was no significant difference between flow-mediated dilation (FMD) at
      baseline and after 12 weeks (0.15 +/- 0.02 vs. 0.14 +/- 0.03; P = 0.39).
      Similarly, no differences were observed in MBF reserve at baseline and after 12
      weeks (3.31 +/- 0.63 vs. 3.48 +/- 0.89; P = 0.89). FMD was blunted in FH
      patients, at baseline, as compared with validation group (0.08 +/- 0.04 vs. 0.15
      +/- 0.02; P < 0.001) and became similar to that group (0.13 +/- 0.05 vs. 0.14 +/-
      0.03; P = 0.07) after treatment. MBF reserve was blunted at baseline in FH
      patients in comparison with the validation group (2.78 +/- 0.71 vs. 3.31 +/-
      0.63; P = 0.003). After treatment, MBF reserve values were no longer different
      (3.43 +/- 0.66 and 3.48 +/- 0.89; P = 0.84, respectively, for FH and validation
      groups). CONCLUSION: Patients with FH and no obstructive CAD have blunted MBF
      reserve and lower FMD values as compared with healthy volunteers. Both FMD and
      MBF reserve were normalized after atorvastatin treatment.

PMID- 22957728
TI  - Structure, optical properties, and magnetism of the full Zn(1-x)Cu(x)WO4 (0 <= x
      <= 1) composition range.
AB  - Microcrystalline and submicrometer powders of Zn(1-x)Cu(x)WO(4) (0 <= x <= 1)
      have been prepared by a solid-state synthesis from stoichiometric quantities of
      the constituent d-block metal oxide and tungsten oxide as well as from a Pechini
      sol-gel synthesis starting from the d-block metal nitrate and ammonium
      metatungstate. The stoichiometry of the product is confirmed by inductively
      coupled plasma-atomic emission spectrometry (ICP-AES) analysis. X-ray diffraction
      shows that for the entire range of compositions, a single-phase product
      crystallizes in the wolframite structure, with a symmetry-lowering transition
      from P2/c to P1[overline] at x = 0.20, concomitant with the first-order Jahn
      Teller distortion of Cu(2+). Far-IR spectroscopy corroborates that symmetry
      lowering is directly related to the tetragonal distortion within the CuO(6)
      octahedra, with the Zn-O A(u) symmetry mode at 320 cm(-1) (x = 0) splitting into
      two stretches at 295 and 338 cm(-1) (x = 0.3). UV-vis-NIR spectroscopy shows an
      optical absorption edge characteristic of an indirect band gap that linearly
      decreases in energy from 3.0 eV (x = 0) to 2.25 eV (x = 1). SQUID magnetometry
      shows that Zn(1-x)Cu(x)WO(4) (0.1 <= x <= 1) has an effective moment of 2.30 +/-
      0.19 MU(B) per mol copper, typical of Cu(2+) in extended solids. For high
      concentrations of copper (x >= 0.8), two transitions are observed: one at high
      temperature, 82 K (x = 1.0) that decreases to 59 K (x = 0.8), and the Neel
      temperature, 23.5 K (x = 1.0) that decreases to 5.5 K (x = 0.8). For x < 0.8, no
      long-range order is observed. A physical 1:1 mixture of both CuWO(4):ZnWO(4)
      shows magnetic ordering identical to that of CuWO(4).

PMID- 22957730
TI  - Stretch-induced biodegradation of polyelectrolyte multilayer films for drug
      release.
AB  - The design of stimuli-responsive polymer assemblies for the controlled release of
      bioactive molecules has raised considerable interest these two last decades.
      Herein, we report the design of mechanically responsive drug-releasing films made
      of polyelectrolyte multilayers. A layer-by-layer (LbL) reservoir containing
      biodegradable polyelectrolytes is capped with a mechanosensitive LbL barrier and
      responds to stretching by a total enzymatic degradation of the film. This
      strategy is successfully applied for the release in solution of an anticancer
      drug initially loaded within the architecture.

PMID- 22957731
TI  - Florid Cordylobia anthropophaga furuncular myiasis from travel in Nigeria.

PMID- 22957729
TI  - CC4, a dimer of cytisine, is a selective partial agonist at
      alpha4beta2/alpha6beta2 nAChR with improved selectivity for tobacco smoking
      cessation.
AB  - BACKGROUND AND PURPOSE: Many of the addictive and rewarding effects of nicotine
      are due to its actions on the neuronal nicotinic ACh receptor (nAChR) subtypes
      expressed in dopaminergic mesocorticolimbic cells. The partial agonists, cytisine
      and varenicline, are helpful smoking cessation aids. These drugs have a number of
      side effects that limit their usefulness. The aim of this study was to
      investigate the preclinical pharmacology of the cytisine dimer1,2-bisN
      cytisinylethane (CC4). EXPERIMENTAL APPROACH: The effects of CC4 on nAChRs were
      investigated using in vitro assays and animal behaviours. KEY RESULTS: When
      electrophysiologically tested using heterologously expressed human subtypes, CC4
      was less efficacious than cytisine on neuronal alpha4beta2, alpha3beta4, alpha7
      and muscle-type receptors, and had no effect on 5-hydroxytryptamine3 receptors.
      Acting through alpha4beta2 and alpha6beta2 nAChRs, CC4 is a partial agonist of
      nAChR-mediated striatal dopamine release and, when co-incubated with nicotine,
      prevented nicotine's maximal effect on this response. In addition, it had low
      affinity for, and was less efficacious than nicotine and cytisine on the
      alpha3beta4 and alpha7-nAChR subtypes. Like cytisine and nicotine, CC4-induced
      conditioned place preference (CPP), and its self-administration shows an inverted
      U dose-response curve. Pretreatment with non-reinforcing doses of CC4
      significantly reduced nicotine-induced self-administration and CPP without
      affecting motor functions. CONCLUSION AND IMPLICATIONS: Our in vitro and in vivo
      findings reveal that CC4 selectively reduces behaviours associated with nicotine
      addiction consistent with the partial agonist selectivity of CC4 for beta2
      nAChRs. The results support the possible development of CC4 or its derivatives as
      a promising drug for tobacco smoking cessation.

PMID- 22957732
TI  - The activation loop of PKA catalytic isoforms is differentially phosphorylated by
      Pkh protein kinases in Saccharomyces cerevisiae.
AB  - PDK1 (phosphoinositide-dependent protein kinase 1) phosphorylates and activates
      PKA (cAMP-dependent protein kinase) in vitro. Docking of the HM (hydrophobic
      motif) in the C-terminal tail of the PKA catalytic subunits on to the PIF (PDK1
      interacting fragment) pocket of PDK1 is a critical step in this activation
      process. However, PDK1 regulation of PKA in vivo remains controversial.
      Saccharomyces cerevisiae contains three PKA catalytic subunits, TPK1, TPK2 and
      TPK3. We demonstrate that Pkh [PKB (protein kinase B)-activating kinase
      homologue] protein kinases phosphorylate the activation loop of each Tpk in vivo
      with various efficiencies. Pkh inactivation reduces the interaction of each
      catalytic subunit with the regulatory subunit Bcy1 without affecting the specific
      kinase activity of PKA. Comparative analysis of the in vitro interaction and
      phosphorylation of Tpks by Pkh1 shows that Tpk1 and Tpk2 interact with Pkh1
      through an HM-PIF pocket interaction. Unlike Tpk1, mutagenesis of the activation
      loop site in Tpk2 does not abolish in vitro phosphorylation, suggesting that Tpk2
      contains other, as yet uncharacterized, Pkh1 target sites. Tpk3 is poorly
      phosphorylated on its activation loop site, and this is due to the weak
      interaction of Tpk3 with Pkh1 because of the atypical HM found in Tpk3. In
      conclusion, the results of the present study show that Pkh protein kinases
      contribute to the divergent regulation of the Tpk catalytic subunits.

PMID- 22957733
TI  - The relationship between the levels of nurses' competence and the length of their
      clinical experience: a tentative model for nursing competence development.
AB  - AIMS AND OBJECTIVES: To explore the relationship between the levels of nurses'
      competence and the length of their clinical experience, in order to provide a
      tentative model of the continuing competence of nurses. BACKGROUND: The
      professional development of employees has attracted great interest. This interest
      has led to the development of various models that illustrate how employees
      develop their competence throughout their careers. However, little is known of
      how nurses maintain and develop their competence throughout their career
      pathways. DESIGN: A cross-sectional design was used. METHODS: Using a survey
      method, five dimensions of self-assessed nursing competence and the length of the
      nurses' clinical practice were measured (n = 325). Each dimension of competence
      was plotted against the length of their clinical experience using locally
      weighted scatterplot smoothing. Then, the shapes of the plots were analysed by
      fractional polynomial regression analysis. RESULTS: Overall, the relationships
      between the levels of nursing competence and the length of clinical experience
      were illustrated by curves with a rapid increase in competence levels at the
      early stage of the nursing career and a slower increase later. These curves were
      modelled by either a logarithmic, square-root function or its reciprocal. The
      results supported the learning curve model. CONCLUSIONS: The competence
      development of nurses may be characterised by two distinctive periods: a rapid
      growth period followed by stable periods. However, the modality of the growth may
      be different depending on which dimension of nursing competence is in focus.
      RELEVANCE TO CLINICAL PRACTICE: The level of nursing competence directly affects
      the quality of care provided to patients. The findings of the study enable
      healthcare organisations to take proactive approaches to enhance nurses'
      competence by identifying when and how to assist nurses.

PMID- 22957734
TI  - Hydrogen/deuterium exchange mass spectrometry reveals specific changes in the
      local flexibility of plasminogen activator inhibitor 1 upon binding to the
      somatomedin B domain of vitronectin.
AB  - The native fold of plasminogen activator inhibitor 1 (PAI-1) represents an active
      metastable conformation that spontaneously converts to an inactive latent form.
      Binding of the somatomedin B domain (SMB) of the endogenous cofactor vitronectin
      to PAI-1 delays the transition to the latent state and increases the thermal
      stability of the protein dramatically. We have used hydrogen/deuterium exchange
      mass spectrometry to assess the inherent structural flexibility of PAI-1 and to
      monitor the changes induced by SMB binding. Our data show that the PAI-1 core
      consisting of beta-sheet B is rather protected against exchange with the solvent,
      while the remainder of the molecule is more dynamic. SMB binding causes a
      pronounced and widespread stabilization of PAI-1 that is not confined to the
      binding interface with SMB. We further explored the local structural flexibility
      in a mutationally stabilized PAI-1 variant (14-1B) as well as the effect of
      stabilizing antibody Mab-1 on wild-type PAI-1. The three modes of stabilizing PAI
      1 (SMB, Mab-1, and the mutations in 14-1B) all cause a delayed latency
      transition, and this effect was accompanied by unique signatures on the
      flexibility of PAI-1. Reduced flexibility in the region around helices B, C, and
      I was seen in all three cases, which suggests an involvement of this region in
      mediating structural flexibility necessary for the latency transition. These data
      therefore add considerable depth to our current understanding of the local
      structural flexibility in PAI-1 and provide novel indications of regions that may
      affect the functional stability of PAI-1.

PMID- 22957735
TI  - Pharmacological or genetic blockade of the dopamine D3 receptor increases cell
      proliferation in the hippocampus of adult mice.
AB  - Dopamine plays an important role in cellular processes controlling the functional
      and structural plasticity of neurons, as well as their generation and
      proliferation, both in the developing and the adult brain. The precise roles of
      individual dopamine receptors subtypes in adult neurogenesis remain poorly
      defined, although D3 receptors are known to be involved in neurogenesis in the
      subventricular zone. By contrast, very few studies have addressed the influence
      of dopamine and D3 receptors upon neurogenesis in the subgranular zone of the
      hippocampus, an issue addressed herein employing constitutive D3 receptor
      knockout mice, or chronic exposure to the preferential D3 receptor antagonist,
      S33138. D3 receptor knockout mice revealed increased baseline levels of cell
      proliferation and ongoing neurogenesis, as measured both using Ki-67 and
      doublecortin, whereas there was no difference in cell survival as measured by
      BrdU (5-bromo-2'-deoxyuridine). Chronic administration of S33138 was shown to be
      functionally active in enhancing levels of the plasticity-related molecule, delta
      FosB, in the D3 receptor-rich nucleus accumbens. In accordance with the
      stimulated neurogenesis seen in D3 receptor knockout mice, S33138 increased
      proliferation in wild-type mice. These observations suggest that D3 receptors
      exert a tonic, constitutive inhibitory influence upon adult hippocampal
      neurogenesis.

PMID- 22957736
TI  - Current trends in paediatric and neonatal ventilatory care -- a nationwide
      survey.
AB  - AIM: To assess daily practices in paediatric and neonatal ventilatory care in
      Finland. METHODS: All neonatal and paediatric intensive care units in Finland
      were sent a questionnaire on ventilatory strategies and were offered a 3-month
      prospective survey. RESULTS: A total of 96% of units returned the questionnaire,
      and clinicians agreed on most of the principles of lung-protective ventilation.
      Seventeen hospitals (94%) joined the prospective survey. On average, 2.3 new
      ventilation episodes were started daily, and totally 211 episodes were monitored.
      Pulmonary problems (64%) were the main cause of treatment in neonates and
      postoperative care (68%) in older children. Synchronized intermittent mandatory
      ventilation with pressure support was the primary mode in 42% of episodes.
      Hypocapnia was observed repeatedly in all units. In adult intensive care units,
      children often received high oxygen fraction, leading to hyperoxia, and they were
      frequently sedated with propofol, which is not licensed for that purpose. A large
      proportion of children had only light sedation or no sedation at all. Despite the
      different strategies and practices, most episodes resulted in a favourable
      outcome. CONCLUSION: Most of the principles of lung-protective ventilation have
      been well accepted by clinicians. More attention should be paid to achieving
      normocapnia and normoxia and to the correct use of sedatives, especially in units
      that only occasionally provide paediatric ventilation.

PMID- 22957737
TI  - Prevalence of asthma and atopic dermatitis in children with special emphasis on
      birth order.

PMID- 22957738
TI  - Steady-state homogeneous nucleation and growth of water droplets: extended
      numerical treatment.
AB  - The steady-state homogeneous vapor-to-liquid nucleation and the succeeding liquid
      droplet growth process are studied for water systems by means of the coarse
      grained molecular dynamics simulations with the mW model suggested originally by
      Molinero et al. [Molinero, V.; Moore, E. B. J. Phys. Chem. B 2009, 113, 4008
      4016]. The investigation covers the temperature range 273 <= T/K <= 363 and the
      system's pressure p ~/= 1 atm. The thermodynamic integration scheme and the
      extended mean first passage time method as tools to find the nucleation and
      cluster growth characteristics are applied. The surface tension is numerically
      estimated and is compared with the experimental data for the considered
      temperature range. We extract the nucleation characteristics such as the steady
      state nucleation rate, the critical cluster size, the nucleation barrier, and the
      Zeldovich factor and perform the comparison with the other simulation results and
      test the treatment of the simulation results within the classical nucleation
      theory. We found that the liquid droplet growth is unsteady and follows the power
      law. Also, the growth laws exhibit the features unified for all of the considered
      temperatures. The geometry of the nucleated droplets is also studied.

PMID- 22957739
TI  - Time-resolved, confocal single-molecule tracking of individual organic dyes and
      fluorescent proteins in three dimensions.
AB  - We demonstrate following individual fluorescent protein constructs and individual
      organic dyes as they diffuse in 3-D in solution at rates up to 1 MUm(2)/s over
      distances of several micrometers in X, Y, and Z. Our 3-D tracking method is
      essentially a stage scanning confocal microscope that uses a unique spatial
      filter geometry and active feedback 200 times/s to follow fast 3-D motion. Here
      we detail simulations used to find optimal feedback parameters for following
      individual fluorescent proteins in 3-D and show that a wide range of parameters
      are capable of following individual proteins diffusing at 1 MUm(2)/s rates. In
      addition, we experimentally show that through 3-D single-molecule tracking of a
      protein oligomer series (monomer, dimer, and tetramer) of the fluorescent protein
      Azami Green one can determine the protein oligomerization state. We also perform
      time-resolved spectroscopy (photon pair correlation measurements) during the
      measured 3-D trajectories. The photon pair correlation measurements show clear
      fluorescence photon antibunching, demonstrating that the trajectories are of
      single fluorescent molecules. We note that the rates of single-molecule diffusive
      motion we follow (approximately 1 MUm(2)/s) are comparable to or faster than many
      intracellular transport processes.

PMID- 22957740
TI  - N-methylated tryptamine derivatives in citrus genus plants: identification of
      N,N,N-trimethyltryptamine in bergamot.
AB  - The occurrence of N-methylated tryptamine derivatives in bergamot plant (Citrus
      bergamia Risso et Poit) is reported for the first time. Interestingly, the most
      abundant of these substances is N,N,N-trimethyltryptamine, which has not been
      previously identified in any citrus plant. The N-methylated tryptamine
      derivatives were identified and quantitated in leaves, peel, juice, and seeds by
      high-performance liquid chromatography-electrospray ionization-tandem mass
      spectrometry. N,N,N-Trimethyltryptamine was confirmed by MS(3) and comparison
      with the synthesized authentic standard. In addition, the study of the
      distribution of tryptophan, tryptamine, N-methyltryptamine, N,N
      dimethyltryptamine, and N,N,N-trimethyltryptamine indicated that these compounds
      are differently expressed in the various tissues of the bergamot plant.
      Intriguingly, chemically synthesized N,N,N-trimethyltryptamine was reported to
      possess nicotine-like activity being a stimulant of parasympathetic ganglia by
      exerting its action on acetylcholine receptors. On this basis, the identification
      of N,N,N-trimethyltryptamine at a relatively high level in leaves suggests a
      possible role in a physiological mechanism of plant defense.

PMID- 22957741
TI  - Importance of direct macrophage-tumor cell interaction on progression of human
      glioma.
AB  - We previously showed tumor-associated macrophages/microglia (TAMs) polarized to
      the M2 phenotype were significantly involved in tumor cell proliferation and poor
      clinical prognosis in patients with high grade gliomas. However, the detailed
      molecular mechanisms involved in the interaction between TAMs and tumor cells
      have been unclear. Current results reveal that, in coculture with human
      macrophages, BrdU incorporation was significantly elevated in glioma cells, and
      signal transducer and activator of transcription-3 (Stat3) activation was found
      in both cell types. Direct mixed coculture led to stronger Stat3 activation in
      tumor cells than did indirect separate coculture in Transwell chamber dishes.
      Screening with an array kit for phospho-receptor tyrosine kinases revealed that
      phosphorylation of macrophage-colony stimulating factor receptor (M-CSFR, CD115,
      or c-fms) is possibly involved in this cell-cell interaction; M-CSFR activation
      was detected in both cell types. Coculture-induced tumor cell activation was
      suppressed by siRNA-mediated downregulation of the M-CSFR in macrophages and by
      an inhibitor of M-CSFR (GW2580). Immunohistochemical analysis of phosphorylated
      (p)M-CSFR, pStat3, M-CSF, M2 ratio, and MIB-1(%) in high grade gliomas revealed
      that higher staining of pM-CSFR in tumor cells was significantly associated with
      higher M-CSF expression and higher MIB-1(%). Higher staining of pStat3 was
      associated with higher MIB-1(%). High M2 ratios were closely correlated with high
      MIB-1(%) and poor clinical prognosis. Targeting these molecules or deactivating
      M2 macrophages might be useful therapeutic strategies for high grade glioma
      patients.

PMID- 22957742
TI  - Bilateral severe anterior uveitis after unilateral selective laser
      trabeculoplasty.

PMID- 22957743
TI  - Metabolic outcomes in young children with type 1 diabetes differ between
      treatment centers: the Hvidoere Study in Young Children 2009.
AB  - OBJECTIVE: To investigate whether center differences in glycemic control are
      present in prepubertal children <11 yr with type 1 diabetes mellitus. RESEARCH
      DESIGN AND METHODS: This cross-sectional study involved 18 pediatric centers
      worldwide. All children, <11 y with a diabetes duration >=12 months were invited
      to participate. Case Record Forms included information on clinical
      characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe
      hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c)
      was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%;
      IFFC: 25-45 mmol/mol). RESULTS: A total of 1133 children participated (mean age:
      8.0 +/- 2.1 y; females: 47.5%, mean diabetes duration: 3.8 +/- 2.1 y). HbA1c
      (overall mean: 8.0 +/- 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency
      (mean 21.7 events per 100 patient-years), but not DKA, differed significantly
      between centers (p < 0.001 resp. p = 0.179). Language difficulties showed a
      negative relationship with HbA1c (8.3 +/- 1.2% vs. 8.0 +/- 1.0%; p = 0.036).
      Frequency of blood glucose monitoring demonstrated a significant but weak
      association with HbA1c (r = -0.17; p < 0.0001). Although significant different
      HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p <
      0.001), center differences remained after adjusting for insulin regimen (p <
      0.001). Differences between insulin regimens were no longer significant after
      adjusting for center effect (p = 0.199). CONCLUSIONS: Center differences in
      metabolic outcomes are present in children <11 yr, irrespective of diabetes
      duration, age, or gender. The incidence of severe hypoglycemia is lower than in
      adolescents despite achieving better glycemic control. Insulin regimens show a
      significant relationship with HbA1c but do not explain center differences. Each
      center's effectiveness in using specific treatment strategies remains the key
      factor for outcome.

PMID- 22957745
TI  - Plasma Lp-PLA(2)  mass and apoB-lipoproteins that carry Lp-PLA(2)  decrease after
      sodium.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2) ) is a novel
      cardiovascular risk marker, which is predominantly complexed to apolipoprotein
      (apo) B-containing lipoproteins in human plasma. As increasing dietary sodium
      intake may decrease plasma apoB-containing lipoproteins, we tested whether a
      sodium challenge lowers plasma Lp-PLA(2) mass, as well as the levels of apoB
      containing lipoprotein particles carrying Lp-PLA(2) (apoB-Lp-PLA(2) ), employing
      a newly developed enzyme-linked immunosorbent assay. MATERIALS AND METHODS: In 45
      women and 31 men (mean age 44 +/- 14 years), plasma Lp-PLA(2) mass (turbidimetric
      immunoassay), the level of apoB-Lp-PLA(2) , expressed in apoB concentration and
      lipoproteins were measured in response to a 3-day challenge with 9 g sodium
      chloride tablets daily. RESULTS: Urinary sodium excretion increased from 165 +/-
      60 to 321 +/- 70 mmol/24 h (P<0.001) after salt loading. Plasma Lp-PLA(2) mass
      decreased from 618 (493-719) to 588 (465-698) MUg/L (P<0.001), and apoB-Lp-PLA(2)
      decreased from 0.276 (0.200-0.351) to 0.256 (0.189-0.328) g LDL protein/L
      (P=0.004) in response to the sodium challenge together with decreases in plasma
      total cholesterol, nonhigh-density lipoprotein (HDL) cholesterol, low-density
      lipoprotein (LDL) cholesterol, apolipoprotein B and the total cholesterol/HDL
      cholesterol ratio (P<0.01 for all). Changes in plasma Lp-PLA(2) mass were
      correlated positively with changes in total cholesterol, LDL cholesterol and non
      HDL cholesterol (r=0.260-0.276, P<0.05 to P<0.02), whereas changes in apoB-Lp
      PLA(2) were correlated positively with changes in non-HDL cholesterol and in the
      total cholesterol/HDL cholesterol ratio (r=0.232-0.385, P<0.05-0.01). CONCLUSION:
      Both plasma Lp-PLA(2) mass levels and apoB-Lp-PLA(2) decrease in response to a
      short-term oral sodium challenge.

PMID- 22957746
TI  - Search for conglomerate in set of [7]helquat salts: multigram resolution of
      helicene-viologen hybrid by preferential crystallization.
AB  - Investigation of a set of 12 [7]helquat salts by X-ray crystal diffraction led to
      identification of conglomerate behavior in bis(trifluoroacetate) salt
      [2][CF(3)CO(2)](2). This is to demonstrate that a systematic search for
      conglomerates can be performed for a given helicenoid enabling straightforward
      multigram resolution via preferential crystallization. Subsequently, preferential
      crystallization of this chiral helicene-viologen hybrid has been established to
      obtain pure P and M enantiomers on a multigram scale, 5 g each. Furthermore,
      preparation of nonracemic samples of [7]helquat 2 via diastereomeric (R,R)
      dibenzoyltartrate salts is described, and determination of absolute configuration
      and racemization barrier is also reported.

PMID- 22957744
TI  - Modulation of DNA damage tolerance in Escherichia coli recG and ruv strains by
      mutations affecting PriB, the ribosome and RNA polymerase.
AB  - RecG is a DNA translocase that helps to maintain genomic integrity. Initial
      studies suggested a role in promoting recombination, a possibility consistent
      with synergism between recG and ruv null alleles and reinforced when the protein
      was shown to unwind Holliday junctions. In this article we describe novel
      suppressors of recG and show that the pathology seen without RecG is suppressed
      on reducing or eliminating PriB, a component of the PriA system for replisome
      assembly and replication restart. Suppression is conditional, depending on
      additional mutations that modify ribosomal subunit S6 or one of three subunits of
      RNA polymerase. The latter suppress phenotypes associated with deletion of priB,
      enabling the deletion to suppress recG. They include alleles likely to disrupt
      interactions with transcription anti-terminator, NusA. Deleting priB has a
      different effect in ruv strains. It provokes abortive recombination and
      compromises DNA repair in a manner consistent with PriB being required to limit
      exposure of recombinogenic ssDNA. This synergism is reduced by the RNA polymerase
      mutations identified. Taken together, the results reveal that RecG curbs a
      potentially negative effect of proteins that direct replication fork assembly at
      sites removed from the normal origin, a facility needed to resolve conflicts
      between replication and transcription.

PMID- 22957747
TI  - The impact of hospitalization on dental plaque accumulation: an observational
      study.
AB  - AIM: To investigate the effect of hospitalization on oral health as assessed by
      dental plaque. MATERIALS AND METHODS: Observational study in a critical care unit
      (CCU). Participants were recruited within 24 h of admission. Dental plaque amount
      was assessed at baseline, 1 and 2 weeks using the Debris index-soft deposits
      (Greene & Vermillion 1960). RESULTS: Fifty participants were recruited with 36
      available for outcome assessment at 1 week and 10 at 2 weeks. The principal
      reason for losses was early discharge with no evidence of a difference between
      patients present only at baseline and those present at 1 week. The median value
      for dental plaque at baseline was 4 (95% CI: 4, 6). The median dental plaque
      increase from baseline to week 1 was 1.5 (95% CI: -1, 4), and this was
      statistically significant (p = 0.04). The median increase from week 1 to week 2
      was 1.0 (95% CI -8, 6) and not statistically significant (p = 0.68). CONCLUSIONS:
      Oral health as assessed by dental plaque deteriorates following hospitalization
      in CCU. Such change could lead to impairment of quality of life and well-being as
      well as to increasing the risk of important healthcare-associated infections such
      as nosocomial pneumonia.

PMID- 22957748
TI  - MUC4-specific CTLs.

PMID- 22957749
TI  - Enhanced detection of infectious salmon anaemia virus using a low-speed
      centrifugation technique in three fish cell lines.
AB  - Infectious salmon anaemia (ISA), caused by ISA virus (ISAV), is a serious disease
      of farmed Atlantic salmon, Salmo salar L. Recently, molecular- and
      immunofluorescent-based techniques have become powerful diagnostic tools for ISAV
      detection, but culture-based techniques remain the gold standard. A disadvantage
      of ISAV culture is that the incubation time required before cytopathic effect
      (CPE) is observed in cell monolayers. To decrease time until CPE is observed, a
      low-speed centrifugation technique was applied to existing standard operating
      procedures for ISAV culture in three fish cell lines. Time until CPE observation
      was compared in CHSE, SHK and ASK cells, treated or not treated with low-speed
      centrifugation after inoculation with ISAV. Low-speed centrifugation treatment
      significantly enhanced observable cell infection. Compared to control cells, the
      length of time until ISAV CPE observation decreased in centrifuged ASK and CHSE
      cells. Low-speed centrifugation was also incorporated into a modified clinical
      shell vial assay. At 48 h post-inoculation with approximately 20 viral particles,
      ISAV was detected by an immunofluorescence antibody test in treated ASK and SHK1
      cells but not in control cells. Finally, this enhanced viral adsorption assay
      performed in ASK cells demonstrated higher sensitivity than a real-time RT-PCR
      assay performed on RNA isolated from ISAV-spiked salmon kidney homogenates.

PMID- 22957750
TI  - Retraction.

PMID- 22957751
TI  - Immunomodulatory effects of Bacillus subtilis (natto) B4 spores on murine
      macrophages.
AB  - To investigate the immunomodulatory effects of Bacillus subtilis (B. subtilis)
      (natto) B4 spores on murine macrophage, RAW 264.7 cells were cultured alone or
      with B subtilis (natto) B4 spores at 37 degrees C for 12 hrs, then both cells and
      culture supernatants were collected for analyses. Exposure of RAW 264.7 cells to
      B. subtilis (natto) B4 spores had no significant effects on macrophage viability
      and amounts of extracellular lactate dehydrogenase (LDH). However, it remarkably
      increased the activities of acid phosphatase (ACP), lactate dehydrogenase (LDH)
      and inducible nitric oxide synthase (iNOS) in cells and the amounts of nitric
      oxide (NO) and cytokines (tumor necrosis factor-alpha, interferon-gamma,
      interleukin [IL]-1 beta, IL-6, IL-12, IL-10 and macrophage inflammatory protein
      2) in culture supernatants. These results demonstrate that B. subtilis (natto) B4
      spores are harmless to murine macrophages and can stimulate their activation
      through up-regulation of ACP and LDH activities and enhance their immune function
      by increasing iNOS activity and stimulating NO and cytokine production. The above
      findings suggest that B. subtilis (natto) B4 spores have immunomodulatory effects
      on macrophages.

PMID- 22957752
TI  - Joint distraction: a treatment to consider for haemophilic arthropathy.

PMID- 22957753
TI  - The use of inside-outside screws for occipitocervical fusion in pediatric
      patients.
AB  - OBJECT: The authors describe the use of inside-outside occipital screws in 21
      children with occipitocervical instability requiring occipitocervical fusion.
      METHODS: The ages of the patients were from 2 to 15 years, and patients presented
      with a variety of causes of occipitocervical instability, including congenital
      disorders, posttraumatic instability, idiopathic degeneration, and postoperative
      instability. Surgeries frequently included foramen magnum decompression,
      duraplasty, and laminectomy, but all patients required occipitocervical
      instrumentation and arthrodesis. Postoperative orthosis included the use of
      either a cervical collar or halo device. In all but one case, patients were
      followed postoperatively for at least 12 months. RESULTS: The mean age of
      patients was 9.93 years. Inside-outside screws were used in all reported cases.
      Rib autograft was used in all patients. In addition, demineralized bone matrix
      was used in 2 cases, and bone morphogenetic protein was used in 2 patients. Two
      patients required halo placement, and the other 19 were placed in cervical
      collars. The average time postoperative orthotics were used was 2.82 months.
      Arthrodesis was determined radiographically and was noted in all patients. No
      operative complications were noted; however, postoperative complications included
      1 wound infection, 2 cases of hardware loosening, and the need for tracheostomy
      in 2 patients. CONCLUSIONS: Inside-outside screws were found to be a useful
      component of occipitocervical instrumentation in pediatric patients ranging from
      2 to 15 years of age. Arthrodesis was demonstrated in all cases.

PMID- 22957754
TI  - Feasibility of repeat surgery for pediatric brain tumors: an objective assessment
      of perioperative outcomes.
AB  - OBJECT: Repeat surgery for pediatric brain tumors is gaining acceptance, with
      extent of resection an important predictor of outcome. However, repeat surgeries
      may be associated with increased morbidity. Few studies in the literature provide
      such outcomes objectively. The authors report on their experience with repeat
      surgery at a tertiary care neurooncology referral center in India. METHODS: A
      prospectively maintained database documented epidemiological, clinical,
      radiological, operative, and perioperative events. The authors analyzed 117
      children (younger than 18 years of age) who had undergone various resective
      surgeries for brain tumors over a period of 5 years. Assessed end points included
      immediate postoperative neurological status, neurological outcome at discharge,
      regional complications, systemic complications, overall morbidity, and mortality.
      RESULTS: The majority of children (48%) were between 3 and 10 years of age.
      Elevated intracranial pressure (70% of patients) and neurological deficits (60%
      of patients) were the commonest presenting symptoms. A significant proportion of
      patients (35%) had a poor Karnofsky Performance Scale score (<= 70).
      Supratentorial procedures were performed in 58% of the patients. Most patients
      (72%) had large (> 4 cm) tumors. Fifty-eight patients (50%) had received prior
      treatment, surgery in 55. Neurological morbidity (worsening), regional
      complications, and systemic complications occurred in 27%, 32%, and 25% of
      patients overall, respectively. Overall morbidity was 44.4% (26.5% major), and
      perioperative mortality was 7.7%. Neurological worsening occurred more frequently
      in patients undergoing a first surgery (p = 0.038), whereas wound-related
      complications were more common in those undergoing reoperations (p = 0.00).
      CONCLUSIONS: Pediatric patients had larger tumors and were more likely to present
      with a poor performance status, often after prior treatment, than their adult
      counterparts. Wound-related complications were higher in the previously treated
      subgroup; however, neurological complications were fewer, probably because of a
      favorable selection of patients. Despite the unavailability of advanced
      intraoperative aids, acceptable levels of overall morbidity and mortality could
      be achieved in repeat surgeries for pediatric brain tumors.

PMID- 22957755
TI  - Case of the disappearing subdural hygromas in a pediatric patient with acute
      lymphocytic leukemia.
AB  - The authors report the case of a 16-year-old boy with pre-B cell acute
      lymphocytic leukemia diagnosed 2 weeks earlier. On workup for diffuse headaches
      he was found to have 10-mm bilateral subdural hygromas with compression of the
      underlying gyri. He was followed clinically, and 4 days after his initial
      presentation he underwent MRI studies of the brain, which showed complete
      resolution of the subdural fluid collections. No change in management was noted
      during these 4 days. This case is the first known instance of rapid,
      spontaneously disappearing bilateral subdural hygromas in a pediatric patient.

PMID- 22957756
TI  - Long-term follow-up of surgically treated juvenile patients with Moyamoya
      disease.
AB  - OBJECT: Surgical revascularization is considered an effective treatment for
      juvenile patients with moyamoya disease (MMD). Yet the long-term outcome in
      surgically treated patients still needs to be clarified. More than 30 years have
      passed since the authors' department started intensively treating pediatric
      patients with MMD using indirect anastomosis techniques. In this study the
      authors surveyed the current status of these patients. METHODS: Activities of
      daily living (ADLs) were surveyed and present clinical status was assessed based
      on the modified Rankin scale (mRS). Cerebrovascular events subsequent to surgical
      treatment were also recorded. RESULTS: Since 1979, 208 patients younger than 19
      years of age with MMD were surgically treated and followed up for > 3 years. Data
      were available on 172 patients (83%), who had been followed up for a mean of 14.3
      years (range 3-32 years). Activity of daily living outcomes were as follows: 138
      patients (80.2%) had mRS scores of 0-2, 29 (16.9%) a score of 3, 1 (0.6%) a score
      of 4, 1 (0.6%) a score of 5, and 3 (1.7%) a score of 6. Cerebrovascular events
      occurred 8 or more years after surgery in 6 patients (3.4%), that is, 6
      hemorrhages and 3 infarctions. The cumulative risk of late-onset stroke at 10,
      20, and 30 years after surgical intervention was 0.8%, 6.3%, and 10.0%,
      respectively. CONCLUSIONS: This long-term survey demonstrated that most
      surgically treated pediatric patients with MMD maintain good ADL outcomes.
      However, a significant number of new cerebrovascular events occurred more than 10
      years after the initial surgery. Additional follow-up will help to identify which
      events may occur during the adult years of patients treated as children.

PMID- 22957758
TI  - Endogenous and induced angiogenic characteristics of human chorion-derived stem
      cells.
AB  - Cell-based therapy using stem cells has emerged as one of the pro-angiogenic
      methods to enhance blood vessel growth and sprouting in ischaemic conditions.
      This study investigated the endogenous and induced angiogenic characteristics of
      hCDSC (human chorion-derived stem cell) using QPCR (quantitative PCR) method,
      immunocytochemistry and fibrin-matrigel migration assay. The results showed that
      cultured hCDSC endogenously expressed angiogenic-endogenic-associated genes
      (VEGF, bFGF, PGF, HGF, Ang-1, PECAM-1, eNOS, Ve-cad, CD34, VEGFR-2 and vWF), with
      significant increase in mRNA levels of PGF, HGF, Ang-1, eNOS, VEGFR-2 and vWF
      following induction by bFGF (basic fibroblast growth factor) and VEGF (vascular
      endothelial growth factor). These enhanced angiogenic properties suggest that
      induced hCDSC provides a stronger angiogenic effect for the treatment of
      ischaemia. After angiogenic induction, hCDSC showed no reduction in the
      expression of the stemness genes, but had significantly higher levels of mRNA of
      Oct-4, Nanog (3), FZD9, ABCG-2 and BST-1. The induced cells were positive for
      PECAM-1 (platelet/endothelial cell adhesion molecule 1) and vWF (von Willebrand
      factor) with immunocytochemistry staining. hCDSC also showed endothelial
      migration behaviour when cultured in fibrin-matrigel construct and were capable
      of forming vessels in vivo after implanting into nude mice. These data suggest
      that hCDSC could be the cells of choice in the cell-based therapy for pro
      angiogenic purpose.

PMID- 22957757
TI  - Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor
      2 (PAR(2) ) is involved in vascular function.
AB  - BACKGROUND AND PURPOSE: Proteinase-activated receptors (PARs) and toll-like
      receptors (TLRs) are involved in innate immune responses. The aim of this study
      was to evaluate the possible cross-talk between PAR(2)  and TLR4 in vessels in
      physiological condition and how it varies following stimulation of TLR4 by using
      in vivo and ex vivo models. EXPERIMENTAL APPROACH: Thoracic aortas were harvested
      from both naive and endotoxaemic rats for in vitro studies. Arterial blood
      pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4
      agonist while PAR(2)  activating peptide (AP) was used as a PAR(2)  agonist.
      Aortas harvested from TLR4(-/-)  mice were also used to characterize the PAR(2) 
      response. KEY RESULTS: PAR(2) , but not TLR4, expression was enhanced in aortas
      of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic
      rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced
      PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naive
      and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-)  mice, the
      expression of PAR(2)  was reduced and the PAR(2) AP-induced vasodilatation
      impaired compared with those from wild-type mice and both resveratrol and
      curcumine were ineffective. CONCLUSIONS AND IMPLICATIONS: Cross-talk between
      PAR(2)  and TLR4 contributes to vascular homeostasis.

PMID- 22957759
TI  - Competition between collapse and breakup in nanometer-sized thin rings using
      molecular dynamics and continuum modeling.
AB  - We consider nanometer-sized fluid annuli (rings) deposited on a solid substrate
      and ask whether these rings break up into droplets due to the instability of
      Rayleigh-Plateau-type modified by the presence of the substrate, or collapse to a
      central drop due to the presence of azimuthal curvature. The analysis is carried
      out by a combination of atomistic molecular dynamics simulations and a continuum
      model based on a long-wave limit of Navier-Stokes equations. We find consistent
      results between the two approaches, and demonstrate characteristic dimension
      regimes which dictate the assembly dynamics.

PMID- 22957760
TI  - The reported expression of pain and distress by people with an intellectual
      disability.
AB  - AIMS AND OBJECTIVES: To explore the assumption that people with ID are unable to
      communicate effectively about pain by examining the extent to which they were
      reported as using language and behaviour that was readily understandable to
      others to communicate pain as distinct from distress. BACKGROUND: The healthcare
      needs of people with an intellectual disability (ID) are frequently overlooked or
      dealt with inappropriately. One proposed reason is the difficulty that such
      individuals have in communicating about their pain. DESIGN: A postal
      questionnaire-based mixed method design was used. METHODS: Data from carer
      reports (n = 29) of the ways people with ID supported expressed pain and distress
      were categorised and analysed using descriptive statistics and thematic content
      analysis. RESULTS: Nineteen of the 22 people who used verbal communication were
      reported to express pain using words that would be understandable to someone
      else, often accompanied by behavioural indications of the location of the pain.
      The language and behaviour that were reported as being used to express distress
      was more idiosyncratic, and there was little overlap between this and the ways in
      which pain was expressed. CONCLUSION: The results provide some challenges to the
      view that people with ID are necessarily unable to communicate effectively about
      their pain and support the view that pain and distress can be conceptually
      distinguished and differentially communicated by some people with ID. RELEVANCE
      TO CLINICAL PRACTICE: The results suggest that many people with ID can be active
      participants in describing their experience of pain and that nurses should
      attempt to obtain this information directly from the individual during the
      diagnostic process. Nurses should be mindful of the distinction between pain and
      distress and should not respond to signs of distress in this group as being
      indicative of pain, without carrying out further assessment.

PMID- 22957761
TI  - Eroded valves, recurrent pleural effusions, and ultimately heart-liver
      transplant.
AB  - A patient with eroded tricuspid and pulmonic valves, who eventually developed
      elevated right atrial and systemic venous pressure that led to hepatic cirrhosis
      and recurrent pleural effusion, is presented. The complex issues involved over a
      long period in this patient, who ultimately required combined heart and liver
      transplant, are discussed.

PMID- 22957762
TI  - The distribution and expression of S100A8 and S100A9 in gingival epithelium of
      mice.
AB  - OBJECTIVE AND BACKGROUND: Gingival epithelium protects against bacterial
      infection by producing antimicrobial peptides such as calprotectin. Calprotectin
      consists of proteins S100A8 and S100A9. Although in vitro assay has shown that
      neutrophils and gingival epithelial cells express calprotectin, the expression of
      S100A8 and S100A9 and colocalization of both S100 proteins in gingival tissue in
      vivo are not fully understood. The aim of this study was to investigate the
      distribution of S100A8 and S100A9 expression in gingival epithelium of mice in
      the presence and absence of infection. MATERIALS AND METHODS: A quantitative
      analysis of S100A8 and S100A9 mRNA in junctional epithelium (JE) and oral
      gingival epithelium (OGE) of both germ-free mice and conventional mice was
      performed using laser microdissection and real-time polymerase chain reaction
      (PCR). Confirmation of S100A8 and S100A9 mRNA expression in the JE was conducted
      by fluorescent immunohistochemistry. RESULTS: Real-time PCR analysis indicated
      that S100A8 and S100A9 expressions were mainly detected in JE and only slightly
      or not detected in OGE. Levels of both S100A8 and S100A9 mRNA expression in JE of
      conventional mice were significantly higher than those in JE of germ-free mice.
      Additionally, fluorescent immunohistochemistry showed that S100A8 expression was
      observed in the JE of both conventional and germ-free mice, whereas S100A9 was
      expressed in the JE of conventional but not germ-free mice. CONCLUSION: S100A8
      protein is expressed in JE cells of mice in the presence and in the absence of
      infection with oral bacteria. S100A9 expression in JE cells in the presence of
      microflora is significantly increased compared with the absence of microflora,
      which suggests that S100A9 expression may be induced by infection of microflora.
      The production of calprotectin in gingival epithelial cells may be mediated
      through S100A9 induction by bacterial infection.

PMID- 22957763
TI  - Hepatitis B virus X protein promotes hepatoma cell invasion and metastasis by
      stabilizing Snail protein.
AB  - A high incidence of tumor recurrence and metastasis has been reported in
      hepatocellular carcinoma (HCC) patients with chronic hepatitis B virus (HBV)
      infection. Although the pathological relevance and significance of hepatitis B
      virus X protein (HBx) in HBV-associated hepatocarcinogenesis attracted much
      attention in recent years, the role and molecular mechanism for HBx in hepatoma
      invasion and metastasis remains poorly understood. In the present study, we found
      that HBx expression could induce epithelial-mesenchymal transition in hepatoma
      and hepatic cells. This effect was shown due to stabilized Snail protein through
      activating the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase
      kinase-3beta (PI3K/AKT/GSK-3beta) signal pathway by HBx expression. Functional
      studies revealed that HBx expression could enhance hepatoma cell migration and
      invasion in vitro. Moreover, stable HBx expression could also facilitate
      intrahepatic and distant lung metastasis of HCC in a nude mice tumor metastasis
      model in vivo. The correlation between increased PI3K/AKT/GSK-3beta signaling
      with elevated Snail protein level was also observed in HCC tumor tissues with
      intrahepatic metastasis or chronic HBV infection. These results revealed a novel
      function of HBx in promoting epithelial-mesenchymal transition through Snail
      protein stabilization by activating PI3K/AKT/GSK-3beta signaling, thus
      facilitating tumor invasion and metastasis during HCC progression. This could
      provide a putative molecular mechanism for tumor recurrence and metastasis in HBV
      associated HCC patients.

PMID- 22957764
TI  - Primary glaucoma in three siblings with Werner syndrome.

PMID- 22957765
TI  - Anaphylactic reaction to probiotics. Cow's milk and hen's egg allergens in
      probiotic compounds.
AB  - BACKGROUND: Probiotics are used in the treatment of allergic diseases. We
      investigated the safety of probiotics for subjects with food allergy. MATERIAL
      AND METHODS: Labels of probiotics commercially available in Spain were examined
      to assess their content of cow's milk or hen's egg. Skin prick tests with these
      compounds (20 mg/ml) were performed in five children allergic to cow's milk, five
      children allergic to hen's white egg, and five control subjects non-allergic to
      food. Three serum pools: I (positive-specific IgE to cow's milk and hen's egg
      white proteins), II (positive-specific IgE to cow's milk and negative to hen's
      egg white proteins), and III (negative-specific IgE to cow's milk and positive to
      hen's egg white proteins) were used to detect cow's milk and hen's egg white
      allergens in probiotics. ImmunoCAP((r)) (Phadia), in-house ELISA, SDS-PAGE
      immunoblotting, and inhibition studies of these assays were performed. Proteins
      were quantified by enzyme-immunoassay. RESULTS: Eleven probiotics were studied.
      No label advertised about egg content, eight labels warned about lactose, lactic
      acid or cow's milk, one label claimed to be milk-free, and two gave no
      information. Cow's milk proteins were detected, by at least one lab technique, in
      10/11 probiotics, three over 2.5 mg/kg (21, 52, 112 mg/kg). Hen's egg white
      proteins were detected in 3/11 probiotics, only one had more than 2.5 mg/kg (47
      mg/kg). CONCLUSION: Probiotic compounds may contain hidden allergens of food and
      may not be safe for subjects with allergy to cow's milk or hen's egg.

PMID- 22957766
TI  - Effects of swim training on liver carcinogenesis in male Wistar rats fed a low
      fat or high-fat diet.
AB  - The present study aimed to investigate the beneficial effects of swim training on
      the promotion-progression stages of rat liver carcinogenesis. Male Wistar rats
      were submitted to chemically induced liver carcinogenesis and allocated into 4
      major groups, according their dietary regimen (16 weeks) and swim training of 5
      days per week (8 weeks): 2 groups were fed low-fat diet (LFD, 6% fat) and trained
      or not trained and 2 groups were fed high-fat diet (HFD, 21% fat) and trained or
      not trained. At week 20, the animals were killed and liver samples were processed
      for histological analyses; immunohistochemical detection of persistent or
      remodeling preneoplastic lesions (pPNL and rPNL) expressing placental glutathione
      S-transferase (GST-P) enzyme; or proliferating cell nuclear antigen (PCNA),
      cleaved caspase-3, and bcl-2 protein levels by Western blotting or malonaldehyde
      (MDA) and total glutathione detection by HPLC. Overall analysis indicated that
      swim training reduced the body weight and body fat in both LFD and HFD groups,
      normalized total cholesterol levels in the HFD group while decreased the MDA
      levels, increased glutathione levels and both number of GST-P-positive pPNL and
      hepatocellular adenomas in LFD group. Also, a favorable balance in PCNA, cleaved
      caspase-3, and bcl-2 levels was detected in the liver from the LFD-trained group
      in relation to LFD-untrained group. The findings of this study indicate that the
      swim training protocol as a result of exercise postconditioning may attenuate
      liver carcinogenesis under an adequate dietary regimen with lowered fat intake.

PMID- 22957767
TI  - Acute and chronic shear stress differently regulate endothelial internalization
      of nanocarriers targeted to platelet-endothelial cell adhesion molecule-1.
AB  - Intracellular delivery of nanocarriers (NC) is controlled by their design and
      target cell phenotype, microenvironment, and functional status. Endothelial cells
      (EC) lining the vascular lumen represent an important target for drug delivery.
      Endothelium in vivo is constantly or intermittently (as, for example, during
      ischemia-reperfusion) exposed to blood flow, which influences NC-EC interactions
      by changing NC transport properties, and by direct mechanical effects upon EC
      mechanisms involved in NC binding and uptake. EC do not internalize antibodies to
      marker glycoprotein PECAM(CD31), yet internalize multivalent NC coated with PECAM
      antibodies (anti-PECAM/NC) via a noncanonical endocytic pathway distantly related
      to macropinocytosis. Here we studied the effects of flow on EC uptake of anti
      PECAM/NC spheres (~180 nm diameter). EC adaptation to chronic flow, manifested by
      cellular alignment with flow direction and formation of actin stress fibers,
      inhibited anti-PECAM/NC endocytosis consistent with lower rates of anti-PECAM/NC
      endocytosis in vivo in arterial compared to capillary vessels. Acute induction of
      actin stress fibers by thrombin also inhibited anti-PECAM/NC endocytosis,
      demonstrating that formation of actin stress fibers impedes EC endocytic
      machinery. In contrast, acute flow without stress fiber formation, stimulated
      anti-PECAM/NC endocytosis. Anti-PECAM/NC endocytosis did not correlate with the
      number of cell-bound particles under flow or static conditions. PECAM cytosolic
      tail deletion and disruption of cholesterol-rich plasmalemma domains abrogated
      anti-PECAM/NC endocytosis stimulation by acute flow, suggesting complex
      regulation of a flow-sensitive endocytic pathway in EC. The studies demonstrate
      the importance of the local flow microenvironment for NC uptake by the
      endothelium and suggest that cell culture models of nanoparticle uptake should
      reflect the microenvironment and phenotype of the target cells.

PMID- 22957770
TI  - 1H and 2H NMR spin-lattice relaxation probing water: PEG molecular dynamics in
      solution.
AB  - Nuclear magnetic resonance spin-lattice relaxation times (T(1)) measurements were
      performed in aqueous solutions of poly(ethylene glycol) (PEG) of 6000 Da
      molecular mass to study the dynamical relation between PEG and water molecules at
      different solute concentrations. (1)H-T(1) experiments were carried on at a low
      magnetic field in the time domain (20 MHz) and at a high field (400 MHz) to
      obtain spectral resolution. Two contributing components were identified in each
      proton system, PEG and water, presenting values of T(1) with very different
      orders of magnitude. The approximate matching between the shorter (1)H-T(1)
      values associated with water and PEG has lead us to conclude that there exists a
      network of interactions (hydrogen bonds) between the solute and the solvent,
      which results in the presence of an ordered and dehydrated structure of PEG
      folded or self-assembled in equilibrium with a more flexible monomer structure.
      Dynamic light scattering results were consistent with the formation of PEG
      aggregates, showing a mean size between 40 and 100 nm.

PMID- 22957768
TI  - Systemic mast cell activation disease: the role of molecular genetic alterations
      in pathogenesis, heritability and diagnostics.
AB  - Despite increasing understanding of its pathophysiology, the aetiology of
      systemic mast cell activation disease (MCAD) remains largely unknown. Research
      has shown that somatic mutations in kinases are necessary for the establishment
      of a clonal mast cell population, in particular mutations in the tyrosine kinase
      Kit and in enzymes and receptors with crucial involvement in the regulation of
      mast cell activity. However, other, as yet undetermined, abnormalities are
      necessary for the manifestation of clinical disease. The present article reviews
      molecular genetic research into the identification of disease-associated genes
      and their mutational alterations. The authors also present novel data on familial
      systemic MCAD and review the associated literature. Finally, the importance of
      understanding the molecular basis of inherited mutations in terms of diagnostics
      and therapy is emphasized.

PMID- 22957771
TI  - Visual performance comparison between contact lens-based pinhole and simultaneous
      vision contact lenses.
AB  - BACKGROUND: The aim was to evaluate the visual performance provided with a
      contact lens-based pinhole design against a simultaneous vision multifocal
      contact lens. METHODS: In a cross-over study at the University of Valencia, 22
      presbyopic patients were evaluated using an artificial pupil fitted on the non
      dominant eye and the simultaneous vision PureVision Multifocal contact lenses.
      After one month of contact lens wear, binocular distance visual acuity (BDVA),
      binocular near visual acuity (BNVA), defocus curve, binocular distance contrast
      sensitivity, binocular near contrast sensitivity, and stereoacuity were measured,
      under photopic conditions (85 cd/m(2)). In addition, binocular distance visual
      acuity and binocular distance contrast sensitivity were examined under mesopic
      conditions (5 cd/m(2)). RESULTS: Mean binocular distance visual acuity for
      pinhole and PureVision Multifocal were 0.02 +/- 0.04 and 0.01 +/- 0.04 logMAR
      under photopic conditions and 0.16 +/- 0.06 and 0.12 +/- 0.04 logMAR for
      binocular near visual acuity under mesopic conditions, respectively. No
      statistically significant differences were found between both types of lenses at
      distance for both lighting levels and intermediate distances (p > 0.05). There
      was a significant difference at near vision under photopic conditions (p = 0.03).
      Binocular distance contrast sensitivity revealed statistically significant
      differences between the pinhole system and PureVision Multifocal for six and 12
      cpd (cycles per degree) spatial frequencies at the two luminance levels, while
      for near vision, differences were also significant for 18 cpd. Stereoacuity was
      better with PureVision Multifocal (127 +/- 49.3 seconds of arc) compared with the
      pinhole lens (220.2 +/- 32.3 seconds of arc, p = 0.004). CONCLUSION: Pinhole and
      PureVision Multifocal contact lenses provide good binocular vision for distance
      and functional intermediate vision. Although it was better with the PureVision
      Multifocal, near vision was not satisfactory for either of the two contact lens
      options.

PMID- 22957772
TI  - Guanfacine ER for the treatment of adolescent attention-deficit/hyperactivity
      disorder.
AB  - INTRODUCTION: Guanfacine extended release (GXR) is an alpha 1A noradrenergic
      agonist that has been approved by the FDA for the treatment of Attention
      Deficit/Hyperactivity Disorder (ADHD) as a monotherapy, and as an adjunctive
      therapy to stimulants for the treatment of ADHD in children and adolescents age 6
      - 17. AREAS COVERED: PubMed, the Ovid Medline database, and the PsycInfo database
      were searched using the term 'guanfacine'. Results were then limited to criteria
      such as English and human, from 1990 through December 2011. The resulting yield
      from the comprehensive literature search was 4391 articles. The titles and
      abstracts of all articles were reviewed. Studies were selected for full-text
      review based upon their place in the hierarchy of evidence (e.g., randomized
      controlled trials), relevance and quality of individual studies, and
      generalizability to clinical practice. The search was augmented by further search
      of article reference lists. A total of 15 articles were selected for full-text
      examination. EXPERT OPINION: Due to the absence of positive evidence for the
      efficacy of GXR for monotherapy in adolescents, clinicians should be guarded in
      the use of GXR for monotherapy in adolescents with ADHD. The use of GXR has
      considerable promise as an adjunct to stimulants for other behavioral conditions
      associated with ADHD.

PMID- 22957773
TI  - Genetic variability in populations of the southern chinch bug, Blissus insularis,
      assessed using AFLP analysis.
AB  - Southern chinch bug, Blissus insularis Barber (Heteroptera: Blissidae), is the
      most destructive insect pest of St. Augustine grass, Stenotaphrum secundatum
      Waltz (Kuntze), in the southern United States. The present study is focused on
      assessing genetic variability in five populations of B. insularis collected from
      Texas and Florida where St. Augustine grass is widely grown. The amplified
      fragment length polymorphism technique was used to DNA fingerprint individuals
      from each population (a total of 46 individuals) using five primer combinations
      (EcoRI/MSeI). Analysis of molecular variance results show no evidence to support
      significant genetic variability among Texas and Florida populations of B.
      insularis. Nearly all genetic variation was found to reside within populations
      (95%), with only approximately 3% residing among populations between regions. Low
      G(ST) values obtained from POPGENE and low F(ST) values obtained from the
      analysis of molecular variance both support the conclusion for high levels of
      gene flow resulting from interbreeding and/or migratory events among the
      populations. A Mantel test of Euclidean squared distances showed no correlation
      between the genetic distance and geographic distance matrices of tested
      populations of B. insularis. The results of the present study suggests that gene
      flow is occurring among populations of B. insularis and, therefore, breeders need
      to be aware that this resistance will most likely not remain localized, and it
      has the potential to spread as a result of migratory events.

PMID- 22957769
TI  - Impact of asthma and comorbid allergic rhinitis on quality of life and control in
      patients of Italian general practitioners.
AB  - OBJECTIVE: Asthma is a disease with elevated prevalence within the general
      population. Although general practitioners (GPs) are among the first health-care
      professionals to whom patients refer for their symptoms, there are few
      evaluations of this disease based on data provided by the GPs. The aim of this
      observational study is to assess the impact of asthma and comorbid allergic
      rhinitis on individual/social burden, quality of life, and disease control in
      asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled
      995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions,
      or with asthma-like symptoms during the previous 12 months. Data were collected
      through questionnaires filled out by GPs and patients. RESULTS: Of the 995
      asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had
      asthma alone. The latter, compared to those with R+A, showed significantly lower
      prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of
      mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%,
      and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was
      frequent and increased with disease severity: 87.5% of severe persistent asthma
      patients reported at least one medical consultation in the last 12 months, 37.5%
      emergency department visits, 26.7% hospitalization, and 62.5% limitations in
      daily activities. Control and quality of life were inversely associated with
      disease severity and were worse in patients with R+A than in those with asthma
      alone. CONCLUSIONS: This study showed the negative impact of high severity levels
      and comorbid allergic rhinitis on quality of life of asthmatic patients and on
      individual/social burden due to asthma in an Italian GPs setting.

PMID- 22957774
TI  - Perception of insect feeding by plants.
AB  - The recognition of phytophagous insects by plants induces a set of very specific
      responses aimed at deterring tissue consumption and reprogramming metabolism and
      development of the plant to tolerate the herbivore. The recognition of insects by
      plants requires the plant's ability to perceive chemical cues generated by the
      insects and to distinguish a particular pattern of tissue disruption. Relatively
      little is known about the molecular basis of insect perception by plants and the
      signalling mechanisms directly associated with this perception. Importantly, the
      insect feeding behaviour (piercing-sucking versus chewing) is a decisive
      determinant of the plant's defence response, and the mechanisms used to perceive
      insects from different feeding guilds may be distinct. During insect feeding,
      components of the saliva of chewing or piercing-sucking insects come into contact
      with plant cells, and elicitors or effectors present in this insect-derived fluid
      are perceived by plant cells to initiate the activation of specific signalling
      cascades. Although receptor-ligand interactions controlling insect perception
      have yet not been molecularly described, a significant number of regulatory
      components acting downstream of receptors and involved in the activation of
      defence responses against insects has been reported. Some of these regulators
      mediate changes in the phytohormone network, while others directly control gene
      expression or the redox state of the cell. These processes are central in the
      orchestration of plant defence responses against insects.

PMID- 22957775
TI  - Abstracts for the Viral Hepatitis Congress 2012. September 7-9, 2012. Frankfurt,
      Germany.

PMID- 22957776
TI  - Toddlers' processing of phonological alternations: early compensation for
      assimilation in English and French.
AB  - Using a picture pointing task, this study examines toddlers' processing of
      phonological alternations that trigger sound changes in connected speech. Three
      experiments investigate whether 2;5- to 3-year-old children take into account
      assimilations--processes by which phonological features of one sound spread to
      adjacent sounds--for the purpose of word recognition (e.g., in English, ten
      pounds can be produced as te[mp]ounds). English toddlers (n = 18) show
      sensitivity to native place assimilations during lexical access in Experiment 1.
      Likewise, French toddlers (n = 27) compensate for French voicing assimilations in
      Experiment 2. However, French toddlers (n = 27) do not take into account a
      hypothetical non-native place assimilation rule in Experiment 3, suggesting that
      compensation for assimilation is already language specific.

PMID- 22957780
TI  - Clues...clues...clues....

PMID- 22957779
TI  - Cutaneous gossypiboma: a potential diagnostic pitfall.

PMID- 22957781
TI  - Effects of sequential infections of Caenorhabditis elegans with Staphylococcus
      aureus and Proteus mirabilis.
AB  - Caenorhabditis elegans can be used to study the dynamics of polymicrobial
      infections, specifically those between Gram-positive and Gram-negative bacteria.
      With C. elegans, Proteus mirabilis acts as an opportunistic pathogen and does not
      kill this host. Hence, in the present study, C. elegans was immunochallenged by
      pre-infecting it with the pathogen Staphylococcus aureus in order to study the
      subsequent effect of P. mirabilis on the host. It was found that 12 hrs of S.
      aureus and 80 hrs of subsequent P. mirabilis infection significantly reduced the
      life span of exposed C. elegans by 80%. However, preinfection with S. aureus for
      8 and 4 hrs reduced the life span of C. elegans by only 60 and 30%, respectively.
      Further, there was greater production of reactive oxygen species in the
      sequentially infected samples than in the S. aureus and P. mirabilis controls.
      Real time PCR analysis indicated regulation of candidate immune regulatory genes,
      lysozyme (lys-7), CUB-like proteins (F08G5.6), neuropeptide-like factors (nlp
      29), transcription factors of mitogen-activated protein kinase (ATF-7) and daf-2
      daf-16 (daf-16), insulin-like signaling pathways and C-type lectin (clec-60 and
      clec-87) family members during S. aureus and subsequent P. mirabilis-mediated
      infections, indicating possible roles of, and contributions by, the above factors
      during host immune responses against these sequential infections. The present
      findings demonstrate that S. aureus infections increase the vulnerability of the
      C. elegans host by subverting its immune system, which then permits the
      opportunistic pathogen P. mirabilis to be pathogenic to this host.

PMID- 22957782
TI  - Neonatal jaundice is a risk factor for childhood asthma: a retrospective cohort
      study.
AB  - BACKGROUND: The association between neonatal jaundice and childhood asthma is a
      new finding of two reports. The purpose of the study was to verify their results.
      METHODS: Data from 11,321 children were collected from the National Health
      Insurance Research Database. Their claims data were evaluated from birth to 10 yr
      old. Children were analyzed as case (those with neonatal jaundice) and controls
      (those without neonatal jaundice). The diagnostic criteria for asthma were as
      follows: at least four asthma diagnoses at outpatient services and emergency
      department (ED), or one asthma diagnosis during an admission. In children fitting
      the asthma criteria, those with no asthma diagnosis after 1 yr of age were
      excluded. Mantel-Haenszel's odds ratios were calculated after adjustment for the
      following confounders: preterm/low birth weight, neonatal infection, other
      respiratory conditions, other birth conditions, and gender. Asthma rate, onset
      time, the use of drugs, upper respiratory infection and lower respiratory
      infection (LRI) rates, hospital admission/ED visit rates, and the effect of
      phototherapy were evaluated. RESULTS: After adjustment for the confounding
      factors, the rate of asthma was higher in icteric children (OR: 1.64, 95% CI 1.36
      1.98, p < 0.001), and the influence in females was stronger. There still was an
      association between neonatal jaundice and late onset asthma (asthma onset after 3
      yr of age). In asthmatic children, those with neonatal jaundice have increased
      asthma onset rate before age 6, increased use of inhalant steroids, LRI rates,
      and ED visits for respiratory disease. CONCLUSIONS: Neonatal jaundice increased
      the rate and severity of childhood asthma in subjects aged up to 10 yr and may be
      a risk factor for childhood asthma.

PMID- 22957785
TI  - REG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP-7
      and MMP-9.
AB  - Recent studies have shown that overexpression of regenerating gene family member
      4 (REG4) is associated with the initiation and progression of pancreatic cancer.
      In our study, we explored the role of REG4 in the invasion of pancreatic cancer.
      Real-time PCR and Western blot analysis were used to determine REG4 expression in
      pancreatic cancer cell lines. An MTT assay was carried out to test the effect of
      REG4 on the growth of pancreatic cancer cells. The involvement of REG4 in cancer
      cell invasion was examined by Transwell invasion assay. Two MMPs, MMP-7 and MMP
      9, were identified from a pool of candidate genes as being related to REG4
      induced cell invasion by PCR and Western blotting. Immunohistochemistry was used
      to confirm the correlation between REG4 and the two MMPs. High expression of REG4
      was found in BXPC-3 cells and its culture media. But in PANC-1 and ASPC-1 cell
      lines, REG4 expression levels were very low, and no detectable protein was found
      in the culture medium. The MTT and Transwell invasion assays showed that
      recombinant REG4 protein and BXPC-3 conditioned media significantly promoted the
      proliferation and invasiveness of pancreatic cancer cells. It was also shown that
      MMP-7 and MMP-9 are upregulated by REG4 induction using real-time PCR and Western
      blotting analysis. Immunohistochemical study further verified this result. In
      conclusion, REG4 promotes not only growth but also in vitro invasiveness of
      pancreatic cancer cells by upregulating MMP-7 and MMP-9.

PMID- 22957786
TI  - Intralesional bevacizumab for cutaneous capillary haemangioma associated with
      pregnancy.

PMID- 22957787
TI  - Microvascular regulatory role and increased expression of vascular endothelial
      growth factor receptor type 2 in experimental gingivitis.
AB  - OBJECTIVE: The aim of the present study was to investigate the possible
      microvascular regulatory role of vascular endothelial growth factor receptor type
      2 (VEGFR2) in experimental gingivitis in rats. BACKGROUND: Our previous results
      demonstrated that functionally active VEGFR2s are located in the venules of rat
      gingiva. While there is no remarkable endogenous gingival VEGF production under
      normal circumstances, exogenous VEGF, via VEGFR2, shows venodilatory effects. We
      assumed that VEGF plays an important role in vasoregulatory processes
      (vasodilation, increased permeability, angiogenesis) of gingival inflammation.
      METHODS: Gingivitis was induced by placing ligatures and composite material
      around and between the lower incisors of anesthetized Wistar rats next to the
      gingival margin. Seven days later, VEGFR2 antagonist (ZM323881), was dripped upon
      the labial gingiva next to the lower incisors. Diameter changes of the selected
      gingival venules were measured by vital microscopy. Animals with healthy gingiva
      served as controls. Venule diameter changes were compared to the baseline and to
      control groups (no ligature). Immunohistochemical and Western blot analysis for
      VEGFR2 were utilized. RESULTS: After 15, 30 and 60 min of local application of
      ZM323881, there was a significant venoconstriction in the inflamed gingiva
      compared to the baseline, while no change was recorded in controls. Endothelium,
      smooth muscle cells and pericytes of the gingivitis group showed increased VEGFR2
      expression. CONCLUSION: Our findings suggest that there is an increased VEGF
      production in gingivitis, which may play an important role in vasodilation of rat
      gingival venules.

PMID- 22957788
TI  - Surface sensing and lateral subcellular localization of WspA, the receptor in a
      chemosensory-like system leading to c-di-GMP production.
AB  - Pseudomonas aeruginosa responds to growth on agar surfaces to produce cyclic-di
      GMP, which stimulates biofilm formation. This is mediated by an alternative
      cellular function chemotaxis-like system called Wsp. The receptor protein WspA,
      is bioinformatically indistinguishable from methyl-accepting chemotaxis proteins.
      However, unlike standard chemoreceptors, WspA does not form stable clusters at
      cell poles. Rather, it forms dynamic clusters at both polar and lateral
      subcellular locations. To begin to study the mechanism of Wsp signal transduction
      in response to surfaces, we carried out a structure-function study of WspA and
      found that its C-terminus is important for its lateral subcellular localization
      and function. When this region was replaced with that of a chemoreceptor for
      amino acids, WspA became polarly localized. In addition, introduction of
      mutations in the C-terminal region of WspA that rendered this protein able to
      form more stable receptor-receptor interactions, also resulted in a WspA protein
      that was less capable of activating signal transduction. Receptor chimeras with a
      WspA C-terminus and N-terminal periplasmic domains from chemoreceptors that sense
      amino acids or malate responded to surfaces to produce c-di-GMP. Thus, the amino
      acid sequence of the WspA periplasmic region did not need to be conserved for the
      Wsp system to respond to surfaces.

PMID- 22957789
TI  - Plasmon-tuned silver colloids for SERRS analysis of methemoglobin with preserved
      nativity.
AB  - Optically tuned silver nanoparticles (AgNP's) functionalized with omega
      mercaptoalkanoic acids are synthesized and used as a signal amplifier for the
      surface-enhanced resonance Raman scattering (SERRS) study of heme cofactor in
      methemoglobin (metHb). Even though both mercaptopropionic acid (MPA)- and
      mercaptononanoic acid (MNA)-functionalized AgNP's exemplify vastly enhanced SERRS
      signal of metHb, MNA-AgNP's amplify the SERRS signal amid preservation of the
      nativity of the heme pocket, unlike MPA-AgNP's. The electrostatic interaction
      between MNA-AgNP's and metHb leads to instant signal enhancement with a Raman
      enhancement factor (EF(SERS)) of 4.2 * 10(3). Additionally, a Langmuir adsorption
      isotherm has been employed for the adsorption of metHb on the MNA-AgNP surface,
      which provides the real surface coverage and equilibrium constant (K) of metHb as
      139 nM and 3.6 * 10(8) M(-1), respectively. The lowest detection limit of 10 nM
      for metHb has been demonstrated using MNA-AgNP's besides retaining the nativity
      of the heme pocket.

PMID- 22957790
TI  - Telomerase inhibition by non-nucleosidic compound BIBR1532 causes rapid cell
      death in pre-B acute lymphoblastic leukemia cells.
AB  - Since unlimited proliferative potential has been identified as a major and, to
      date, therapeutically unexploited phenotypic hallmark of cancer, telomere
      maintenance mechanisms have been proposed as potential targets for new anticancer
      interventions. This study was aimed to investigate the effects of BIBR1532, the
      lead compound of non-nucleosidic inhibition of telomerase, on pre-B acute
      lymphoblastic leukemia (ALL) cells. BIBR1532 caused rapid cell death in Nalm-6
      cells probably through transcriptional suppression of survivin-mediated c-Myc and
      human telomerase reverse transcriptase (hTERT) expression in a concentration
      dependent manner. Moreover, our results also suggest that induced p73, up
      regulated Bax/Bcl-2 molecular ratio and subsequent activation of caspase-3 may
      contribute to a direct short-term cytotoxic effect of high doses of BIBR1532,
      independent of long-term substantial telomere erosion-mediated cell cycle arrest.

PMID- 22957791
TI  - Bariatric surgery or medicine for type 2 diabetes?
AB  - Diet and medical treatment are the standard treatment for type 2 diabetes. In
      obese subjects with type 2 diabetes, bariatric surgery is effective in resolving
      diabetes. Two clinical trials comparing bariatric surgery to medical treatment
      were evaluated. Both the Surgical Treatment And Medications Potentially Eradicate
      Diabetes Efficiently (STAMPEDE) trial (laparoscopic Roux-En Y gastric bypass and
      sleeve gastrectomy) and the DIet and medical therapy versus BAriatric SurgerY in
      type 2 diabetes (DIBASY) trial (laparoscopic gastric bypass and biliopancreatic
      diversion) showed that surgery was more effective than medical care in resolving
      or managing type 2 diabetes. Larger studies, or a compilation of studies, are
      needed to determine whether one of these procedures is better, or if they are all
      similarly effective, and this should also be weighed against the risk of the
      operations.

PMID- 22957792
TI  - Triptolide modulates the sensitivity of K562/A02 cells to adriamycin by
      regulating miR-21 expression.
AB  - CONTEXT: Multidrug-resistance is a serious obstacle encountered in leukemia
      treatment. Recent studies have shown microRNA-21 (miR-21) is overexpressed in
      several types of cancer and contributes to tumor resistance to chemotherapy. In
      our previous studies, we found triptolide (TPL) could enhance adriamycin-induced
      cytotoxicity and apoptosis in K562/A02 cells. OBJECTIVE: In the present study, we
      investigated the mechanism of TPL on the sensitivity of K562/A02 cells to
      adriamycin. MATERIALS AND METHODS: Cell viability was assessed by methyl
      thiazolyl tetrazolium (MTT) assay. Expression of mature miR-21 was determined by
      SYBER green PCR. The miR-21 mimics and inhibitors were chemically synthesized and
      transfected into K562 cells or K562/A02 cells. PTEN protein levels was determined
      by western blots. PTEN promoter activity was measured by luciferase assays.
      RESULTS: TPL (5 nmol/L) increased the sensitivity of K562/A02 to adriamycin. When
      adriamycin was combined with 5 nmol/L TPL, the mean apoptotic population of
      K562/A02 cells was increased from 4.3 to 18.5%, respectively. K562/A02 cells
      showed a significant reduction in miR-21 and phosphatase and tensin homolog
      deleted on chromosome ten (PTEN) expressions after TPL treatment. K562/A02 cells
      that were transfected with the miR-21 inhibitor had a significantly higher PTEN
      protein level than the control. K562 cells that were pre-treated with PTEN siRNA
      had increased survival rate compared to the control group. DISCUSSION AND
      CONCLUSION: Our findings indicated that triptolide modulates the sensitivity of
      K562/A02 cells to adriamycin by regulating miR-21 expression. Triptolide
      inhibited miR-21 expression and enhanced PTEN levels in K562/A02 cells.

PMID- 22957795
TI  - A case of aortic stenosis and hypertrophic cardiomyopathy.
AB  - A patient with severe aortic valvular stenosis and coexisting obstructive
      hypertrophic cardiomyopathy, in whom diagnostic difficulties and management
      dilemmas arose, is presented. The complex issues involved in such a combination
      are discussed.

PMID- 22957793
TI  - Methanol extract of dried exudate of Commiphora mukul prevents bone resorption in
      ovariectomized rats.
AB  - CONTEXT: Gum guggul, a resinous exudate of the plant Commiphora mukul Engl.
      (Burseraceae), has been found efficacious in the treatment of bone fractures,
      arthritis, and hyperlipidemic disorders. OBJECTIVE: The present study is an
      effort to explore the anti-bone-resorptive potential of the dried methanol
      extract of the gummy exudate of C. mukul (MECM) in ovariectomized rat model.
      MATERIALS AND METHODS: The animals were randomly divided into five groups of
      equal size (n = 6). Animals in all the groups were ovariectomized except group 1,
      which was sham operated. Groups 3, 4 and 5 were treated with Raloxifene, MECM 250
      mg/kg and MECM 500 mg/kg, respectively. The 2nd group was fed with vehicle.
      ASSESSMENT: biochemical estimations, viz., alkaline phosphatase (ALP), tartarate
      resistant acid phosphatase (TRAP), serum calcium (Ca); biomechanical evaluations,
      and histopathological examinations. RESULTS: The LD(50) of MECM was found to be >
      2500 mg/kg orally. A significant elevation was observed in the ALP, TRAP, Ca and
      cholesterol levels in the 2nd group with a significant reduction in biomechnical
      strength. Groups 3, 4 and 5, showed a significant reduction in TRAP and ALP
      levels (p < 0.001). The Ca levels were normalized in the groups 4 and 5, while
      cholesterol levels dropped in group 5. The bone strength, however, was normalized
      in all the groups (p < 0.001) along with the histopathology. DISCUSSION AND
      CONCLUSION: Findings suggested a significant gain in bone strength and nearly
      complete restoration of bone microarchitecture along with lowered levels of TRAP
      indicating the anti-bone resorptive potential of the extract.

PMID- 22957796
TI  - Synthesis of alkaloid (-)-205B via stereoselective reductive cross-coupling and
      intramolecular [3+2] cycloaddition.
AB  - An asymmetric synthesis of alkaloid (-)-205B, a tricyclic member of the
      architecturally diverse family of natural products isolated from the skin of
      neotropical poison frogs, is described that proceeds through two recently
      developed stereoselective synthetic methods: (1) Ti-mediated allylic alcohol
      imine reductive cross-coupling and (2) intramolecular [3+2] cycloaddition of a
      glyoxylate-based homoallylic nitrone. The utility of this latter cycloaddition
      process for the assembly of the stereochemically dense piperidine core of 205B is
      noteworthy, as this method enables direct [3+2] cycloaddition of an intermediate
      homoallylic (E)-nitrone via a pathway that is stereochemically unscathed by
      competitive [3,3]-sigmatropic rearrangement processes. Overall, the synthesis is
      asymmetric, concise, and highly stereoselective-features which point to the
      potential future utility of these chemical methods in natural product synthesis
      and medicinal chemistry.

PMID- 22957797
TI  - Direct in situ determination of the mechanisms controlling nanoparticle
      nucleation and growth.
AB  - Although nanocrystal morphology is controllable using conventional colloidal
      synthesis, multiple characterization techniques are typically needed to determine
      key properties like the nucleation rate, induction time, growth rate, and the
      resulting morphology. Recently, researchers have demonstrated growth of
      nanocrystals by in situ electron beam reduction, offering direct observations of
      single nanocrystals and eliminating the need for multiple characterization
      techniques; however, they found nanocrystal morphologies consistent with two
      different growth mechanisms for the same electron beam parameters. Here we show
      that the electron beam current plays a role analogous to the concentration of
      reducing agent in conventional synthesis, by controlling the growth mechanism and
      final morphology of silver nanocrystals grown via in situ electron beam
      reduction. We demonstrate that low beam currents encourage reaction limited
      growth that yield nanocrystals with faceted structures, while higher beam
      currents encourage diffusion limited growth that yield spherical nanocrystals. By
      isolating these two growth regimes, we demonstrate a new level of control over
      nanocrystal morphology, regulated by the fundamental growth mechanism. We find
      that the induction threshold dose for nucleation is independent of the beam
      current, pixel dwell time, and magnification being used. Our results indicate
      that in situ electron microscopy data can be interpreted by classical models and
      that systematic dose experiments should be performed for all future in situ
      liquid studies to confirm the exact mechanisms underlying observations of
      nucleation and growth.

PMID- 22957798
TI  - Spectral hole burning, recovery, and thermocycling in chlorophyll-protein
      complexes: distributions of barriers on the protein energy landscape.
AB  - Chlorophyll-protein complexes are ideal model systems for protein energy
      landscape research. Here pigments, used in optical spectroscopy experiments as
      sensitive probes to local dynamics, are built into protein by Nature (in a large
      variety of local environments; without extraneous chemical manipulations or
      genetic engineering). Distributions of the tunneling parameter, lambda, and/or
      protein energy landscape barrier heights, V, have been determined for (the lowest
      energy state of) the CP43 core antenna complex of photosystem II. We demonstrate
      that spectral hole burning (SHB) and hole recovery (HR) measurements are capable
      of delivering important information on protein energy landscape properties and
      spectral diffusion mechanism details. In particular, we show that tunneling
      rather than barrier hopping is responsible for both persistent SHB and subsequent
      HR at 5-12 K, which allows us to estimate the md(2) parameter of the tunneling
      entities as ~1.0 * 10(-46) kg.m(2). The subdistributions of lambda actually
      contributing to the nonsaturated spectral holes (and affecting their recovery)
      differ from the respective full true distributions. In the case of the full
      lambda-distribution being uniform (or the barrier height distribution ~1/?V, a
      model which has been widely employed in theories of amorphous solids at low
      temperatures and in HR analysis), the difference is qualitative, with lambda
      subdistributions probed in the HR experiments being highly asymmetrical, and
      barrier V subdistributions deviating significantly from ~1/?V. Thus, the
      distribution of lambda for the protein energy landscape tier directly probed by
      SHB is likely Gaussian and not uniform. Additionally, a Gaussian distribution of
      barriers, with parameters incompatible with those of the landscape tier directly
      probed by SHB, contributes to the thermocycling results.

PMID- 22957800
TI  - Anatomy of the pectoral and forelimb muscles of wildtype and green fluorescent
      protein-transgenic axolotls and comparison with other tetrapods including humans:
      a basis for regenerative, evolutionary and developmental studies.
AB  - The axolotl Ambystoma mexicanum is one of the most used model organisms in
      evolutionary, developmental and regenerative studies, particularly because it can
      reconstitute a fully functional and complete forelimb/hindlimb. Surprisingly,
      there is no publication that describes all the pectoral and forelimb muscles of
      this species or provides a comparative framework between these muscles and those
      of other model organisms and of modern humans. In the present paper we describe
      and illustrate all these muscles in A. mexicanum and provide the first report
      about the myology of adults of a model organism that is based on analyses and
      dissections of both wildtype animals and transgenic animals that express green
      fluorescent protein (GFP) in muscle fibers. On the one hand, the inclusion of GFP
      transgenic animals allows us to show the muscles as more commonly seen, and thus
      easier to understand, by current developmental and regenerative biologists. On
      the other hand, by including wildtype and GFP-transgenic animals and by
      visualizing these latter animals with and without a simultaneous transmission
      laser light, we were able to obtain a more complete and clearer understanding of
      the exact limit of the fleshy and tendinous parts of the muscles and their
      specific connections with the skeletal elements. This in turn allowed us to
      settle some controversies in previous anatomical and comparative studies. As most
      developmental, regenerative and evolutionary biologists are interested in
      comparing their observations of A. mexicanum with observations in other model
      organisms, and ultimately in using this information to increase the understanding
      of human evolution and medicine, we also provide tables showing the homologies
      between the pectoral and forelimb muscles of axolotls, of model organisms such as
      mice, frogs and chicken, and of Homo sapiens. An example illustrating the
      outcomes of using our methodology and of our observations is that they revealed
      that, contrary to what is often stated in the literature, A. mexicanum has a
      muscle coracoradialis that has both a well developed proximal fleshy belly and a
      distal long and thin tendon, supporting the idea that this muscle very likely
      corresponds to at least part of the amniote biceps brachii. Our observations
      also: (i) confirmed that the flexores digitorum minimi, interphalangeus digiti 3,
      pronator quadratus and palmaris profundus 1 are present as distinct muscles in A.
      mexicanum, supporting the idea that the latter muscle does not correspond to the
      pronator accessorius of reptiles; (ii) confirmed that the so-called extensor
      antebrachii radialis is present as a distinct muscle in this species and,
      importantly, indicated that this muscle corresponds to the supinator of other
      tetrapods; (iii) showed that, contrary to some other urodeles, including some
      other Ambystoma species, there is no distinct muscle epitrochleoanconeus in A.
      mexicanum and; (iv) showed that the ulnar and radial bundles of the abductor et
      extensor digiti 1 correspond to the abductor pollicis longus and extensor
      pollicis longus of other tetrapods, respectively.

PMID- 22957799
TI  - Anticandidal activity and biocompatibility of a rechargeable antifungal denture
      material.
AB  - OBJECTIVES: Candida-associated denture stomatitis is a recurrent and debilitating
      oral mucosal disease. Development of anticandidal denture materials represents a
      promising strategy to manage this condition. We have previously shown that
      miconazole incorporated in methacrylic acid (MAA) copolymerized diurethane
      dimethacrylate (UDMA) denture materials has long-term anticandidal activity. In
      this study, we examined the ability of culture medium conditioned with drug-free-
      or miconazole-MAA-UDMA discs to prevent Candida infection in an in vitro oral
      epithelial cell/Candida albicans coculture system. MATERIALS AND METHODS: Candida
      albicans (C. albicans)-induced OKF6/TERT-2 cell damage was quantified by the
      release of lactate dehydrogenase from epithelial cells, cytokine production was
      quantified using protein cytokine arrays, and the expression of C. albicans genes
      was measured by RT-qPCR. RESULTS: Candida albicans had limited growth with
      altered expression levels of secreted aspartyl proteinase-2 and -5 in culture
      medium conditioned by miconazole-MAA-UDMA discs. Significantly, the ability of C.
      albicans to induce oral epithelial cell damage and trigger epithelial
      proinflammatory cytokine production was also inhibited by miconazole disc
      conditioned media. CONCLUSION: Miconazole released from MAA-UDMA denture
      materials effectively prevents the development of candidal infection in an in
      vitro oral epithelial system. Further characterization of this drug-rechargeable
      denture material is warranted.

PMID- 22957801
TI  - Differences in maturation of the jaw-opening reflex between rats that received
      early-and late-masticatory stimulation.
AB  - The jaw-opening reflex (JOR) plays an important role in the regulation of jaw
      movement during mastication. Previous study showed that altered masticatory
      function during growth impedes JOR maturation and thus may affect masticatory
      performance in adults. However, no studies have compared the benefit of early and
      delayed correction in terms of functional development. Therefore, this study
      tested the hypothesis that early-stimulation of masticatory function during
      growth can promote JOR maturation better than late-stimulation during adulthood.
      Soon after weaning, 120 female Wistar rats were divided into two groups and fed
      either solid (control group) or liquid (experimental group) diets. The
      experimental group was further divided into early-, late-, and non-stimulation
      subgroups. Early- and late-stimulation groups were fed a solid diet instead of a
      liquid diet at 5- and 11-week-old, respectively, whereas non-stimulation group
      was fed only a liquid diet until the end of the experiment. At 3, 5, 7, 9, 11 and
      13 weeks, JOR recordings were conducted in anaesthetised rats of all groups.
      Latency and peak-to-peak amplitude of the JOR were compared between the groups.
      From 7 to 13 weeks, early-stimulation group showed a JOR with short latency and
      high amplitude similar to that of control group. In contrast, late- and non
      stimulation groups showed significantly longer latency and smaller amplitude of
      the JOR than in control group. We demonstrated that early masticatory stimulation
      within the critical period for programming mastication may have greater potential
      to restore JOR maturation to values close to those in normal adults.

PMID- 22957802
TI  - Young word learners' interpretations of words and symbolic gestures within the
      context of ambiguous reference.
AB  - Early in development, many word-learning phenomena generalize to symbolic
      gestures. The current study explored whether children avoid lexical overlap in
      the gestural modality, as they do in the verbal modality, within the context of
      ambiguous reference. Eighteen-month-olds' interpretations of words and symbolic
      gestures in a symbol-disambiguation task (Experiment 1) and a symbol-learning
      task (Experiment 2) were investigated. In Experiment 1 (N = 32), children avoided
      verbal lexical overlap, mapping novel words to unnamed objects; children failed
      to display this pattern with symbolic gestures. In Experiment 2 (N = 32), 18
      month-olds mapped both novel words and novel symbolic gestures onto their
      referents. Implications of these findings for the specialized nature of word
      learning and the development of lexical overlap avoidance are discussed.

PMID- 22957804
TI  - Pentacam anterior chamber parameters in young and middle-aged Chinese.
AB  - BACKGROUND: The aim was to compare the anterior segment of two groups of Chinese
      using the Pentacam system. METHODS: Fifty young (median age 21 years) and 50
      middle-aged (median age 46 years) subjects with equal numbers of males and
      females had their axial length measured with the IOL Master. Their axial anterior
      chamber depth, anterior chamber volume and temporal and nasal anterior chamber
      angles were measured using the Pentacam and comparisons were made between the two
      groups. RESULTS: Both groups shared similar axial lengths (unpaired t-test: p =
      0.37) but young subjects had significantly deeper anterior chamber by 11 per cent
      (3.60 +/- 0.40 mm) compared with middle-aged subjects (3.24 +/- 0.34 mm)
      (analysis of variance: p < 0.001). The anterior chamber volume was significantly
      greater in young subjects by 24 per cent (200.12 +/- 35.59 mm(3)) than the middle
      aged subjects (161.03 +/- 37.79 mm(3)). The associations of anterior chamber
      depth and anterior chamber volume with axial length were significant (R(2) from
      0.16 to 0.50) and similar in both groups. Young subjects had wider anterior
      chamber angles (mean differences: 4.60 degrees  and 6.07 degrees  at temporal and
      nasal, respectively) than middle-aged subjects. Among middle-aged subjects,
      females had significantly shorter axial length but anterior chamber depths were
      similar between the two sexes. Females had significantly smaller anterior chamber
      volumes. CONCLUSIONS: Middle-aged subjects had more crowded anterior chambers
      than young subjects with similar axial lengths. Anterior chamber volume may be a
      more sensitive parameter to reveal this difference than a linear measurement of
      the anterior chamber depth.

PMID- 22957803
TI  - 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor
      potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2
      amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.
AB  - A series of N-(2-amino-6-trifluoromethylpyridin-3-ylmethyl)-2-(3-fluoro-4
      methylsulfonylaminophenyl)propanamides were designed combining previously
      identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR
      analysis indicated that specific hydrophobic interactions of the 2-amino
      substituents in the C-region of the ligand were critical for high hTRPV1 binding
      potency. In particular, compound 49S was an excellent TRPV1 antagonist (K(i(CAP))
      = 0.2 nM; IC(50(pH)) = 6.3 nM) and was thus approximately 100- and 20-fold more
      potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism.
      Furthermore, it demonstrated strong analgesic activity in the rat neuropathic
      model superior to 2 with almost no side effects. Compound 49S antagonized
      capsaicin induced hypothermia in mice but showed TRPV1-related hyperthermia. The
      basis for the high potency of 49S compared to 2 is suggested by docking analysis
      with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C
      region of 49S made additional hydrophobic interactions with the hydrophobic
      region.

PMID- 22957805
TI  - The natural history of Parkinson's disease in the province of Segovia: mortality
      in a longitudinal study (20-year follow-up).
AB  - OBJECTIVE: We determined mortality rates and predictors of survival in 273
      patients with Parkinson's disease based on a 20-year follow-up longitudinal
      study. MATERIAL AND METHODS: We examined 273 patients with Parkinson's disease
      during a 20-year follow-up, recruited between 1978 and 1998. All patients were
      regularly followed at the Department of Neurology until December 31, 1998, or
      death. RESULTS: By then, 69 patients had died, crude mortality was rate 4.43, and
      standardized mortality ratio for the total patient group was 1.39 (95% CI, 1.10
      1.50). As Parkinson's disease is a chronic progressive disorder in adult life,
      disease-related mortality would be expected to increase in later stages after 15
      or 20 years. Mean age at death in our cohort was 78.27 (95% CI, 76.90-79.20).
      Median time of death was 11 years (95% CI, 9.50-12.49). Independent predictors of
      mortality during the follow-up were age at onset (hazard ratio, 1.05; 95% CI,
      1.01-1.09; P = 0.01), clinical form - akinesia and rigidity (hazard ratio, 2.20;
      95% CI, 1.06-4.88; P = 0.03) - and treatment with dopaminergic agonist (hazard
      ratio, 0.49; 95% CI, 0.23-1.03; P = 0.06). Cardiovascular disease was the most
      frequent cause of death in 42%. CONCLUSIONS: This study suggests a link between
      mortality with age of onset and treatment without dopamine agonists as initial
      treatment. So, there is an association between decreased mortality and tremor as
      initial clinical forms at onset.

PMID- 22957806
TI  - Xerostomia in complete denture wearers: prevalence, clinical findings and impact
      on oral functions.
AB  - OBJECTIVES: To investigate the prevalence of dry mouth in a select sample of
      edentulous Jordanian older population wearing complete dentures and to evaluate
      its impact on oral functions. BACKGROUND: The prevalence and impact of Xerostomia
      as a cofactor in causing denture problems in Jordanians have not been previously
      investigated. MATERIALS AND METHODS: This study included 455 participants (253
      men and 202 women). Perception of dry mouth was measured by a pilot-tested
      questionnaire. Xerostomic status was confirmed clinically. Complete denture
      function was also assessed. RESULTS: One hundred and thirty six subjects (29.9%)
      had reported a subjective feeling of dry mouth with a prevalence of 24.9% in men
      (n = 63) and 36.1% in women (n = 73) (p < 0.01). 136 of the 145 subjects with
      satisfactory dentures showed one or more signs suggestive of Xerostomia. The
      majority of xerostomic participants with different sets of complete dentures were
      dissatisfied with oral functions (p < 0.05). There was a significant association
      between dry mouth and increasing age, female gender and smoking status (p <
      0.05). CONCLUSION: Among complete denture wearers, Xerostomia is significantly
      more prevalent in women and associated with increased age and smoking. Xerostomia
      adversely affects oral functions and overall satisfaction with dentures.

PMID- 22957807
TI  - Phenotypic and clinical manifestations of compound heterozygous genetic
      haemochromatosis (CHGH): a non-invasive approach to clinical management.
AB  - BACKGROUND: The role of compound heterozygous genetic haemochromatosis (CHGH)
      (C282Y/H63D) mutations in the manifestations of iron overload is known; however,
      the extent of these manifestations and their associated management remain
      unclear. AIMS: This study evaluates the phenotypic manifestations of CHGH using
      laboratory and radiological biomarkers including serum ferritin/transferrin
      saturation, liver function tests (LFT), thyroid function tests, blood sugar
      level, and abdominal ultrasound (US) or computed tomography. The study also
      evaluates the effects of venesection therapy on these markers and its potential
      role in routine management of CHGH patients. METHODS: In this case-controlled
      study, 104 patients with HFE-C282Y/H63D compound mutations were subjected to
      laboratory investigations and imaging. Tests were repeated over a 4-year period
      before and after venesection. Data were compared between patient and control
      groups using paired t-tests. RESULTS: Patients showed significantly higher serum
      ferritin and transferrin saturations compared with controls (P = 0.002, P =
      0.003). Twenty-four patients (23%) demonstrated hyperferritinaemia >= 1000
      mmol/L. Sixty-nine patients (68%) demonstrated biochemical abnormalities on
      initial testing (abnormal LFT (transaminases) (51 patients, 74%) and US/computed
      tomography (42 patients, 61%)). A significant number of LFT and US abnormalities
      normalised post-venesection (80%; P = 0.000 and 52%; P = 0.005 respectively).
      CONCLUSIONS: Phenotypic manifestations displayed by CHGH patients can include
      biochemical and radiological abnormalities, which can occur at levels similar to
      C282Y homozygous disease (ferritin >= 1000 mmol/L). With venesection therapy, a
      large number of these abnormalities is reversible. Based on this, a non-invasive
      framework to assess and manage CHGH within a routine community-based clinical
      setting is proposed.

PMID- 22957808
TI  - Foetal exposure to maternal stressful events increases the risk of having asthma
      and atopic diseases in childhood.
AB  - BACKGROUND: The natural history of asthma and atopic diseases begins in utero.
      Studies investigating the influence of foetal exposure to maternal stressful life
      events during pregnancy (SLEP) on asthma and atopic diseases are lacking. AIM: To
      test whether the children of mothers who had experienced SLEP are at an increased
      risk for asthma, atopic eczema and allergic rhinitis. METHODS: The association
      between maternal SLEP (at least one among: divorce, mourning or loss of the job)
      and the occurrence of asthma and atopic diseases in childhood was studied in a
      population (n = 3854) of children, aged 3-14 yrs, living in Northern Italy. The
      parents filled in a standardized questionnaire about the children's health and
      the events occurred to their mothers during pregnancy. RESULTS: Three hundred and
      thirty-three (9%) of the mothers experienced SLEP. Their children had a
      statistically significantly higher lifetime prevalence of wheezing (31.6% vs.
      23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) and atopic
      eczema (29.7% vs. 21.1%) than those of mothers without SLEP. After adjusting for
      potential confounders, the foetal exposure to SLEP was positively associated with
      wheezing (OR: 1.41, 95% CI: 1.03-1.94), asthma (OR: 1.71, 95% CI: 1.02-2.89),
      allergic rhinitis (OR: 1.75, 95% CI: 1.08-2.84) and atopic eczema (OR: 1.53, 95%
      CI: 1.11-2.10). CONCLUSION: The children of mothers who had experienced SLEP were
      at a moderately increased risk of having wheezing, asthma, eczema and allergic
      rhinitis during their childhood. Maternal stress during pregnancy might enhance
      the expression of asthma and atopic phenotypes in children.

PMID- 22957809
TI  - Field-effect transistors from lithographically patterned cadmium selenide
      nanowire arrays.
AB  - Field-effect transistors (NWFETs) have been prepared from arrays of
      polycrystalline cadmium selenide (pc-CdSe) nanowires using a back gate
      configuration. pc-CdSe nanowires were fabricated using the lithographically
      patterned nanowire electrodeposition (LPNE) process on SiO(2)/Si substrates.
      After electrodeposition, pc-CdSe nanowires were thermally annealed at 300 
      degrees C * 4 h either with or without exposure to CdCl(2) in methanol-a grain
      growth promoter. The influence of CdCl(2) treatment was to increase the mean
      grain diameter from 10 to 80 nm as determined by grazing incidence X-ray
      diffraction and to convert the crystal structure from cubic to wurtzite. Measured
      transfer characteristics showed an increase of the field effect mobility
      (MU(eff)) by an order of magnitude from 1.94 * 10(-4) cm(2)/(V s) to 23.4 * 10(
      4) cm(2)/(V s) for pc-CdSe nanowires subjected to the CdCl(2) treatment. The
      CdCl(2) treatment also reduced the threshold voltage (from 20 to 5 V) and the
      subthreshold slope (by ~35%). Transfer characteristics for pc-CdSe NWFETs were
      also influenced by the channel length, L. For CdCl(2)-treated nanowires, MU(eff)
      was reduced by a factor of eight as L increased from 5 to 25 MUm. These channel
      length effects are attributed to the presence of defects including breaks and
      constrictions within individual pc-CdSe nanowires.

PMID- 22957810
TI  - Hsp70 and small Hsps are the major heat shock protein members involved in midgut
      metamorphosis in the common cutworm, Spodoptera litura.
AB  - Heat shock proteins (Hsps) are important chaperones, which are involved in
      various signal pathways and regulate lots of physiological processes. Early
      research suggested that some Hsps are involved in insect development. However,
      few studies have been carried out to explore the roles of Hsps, especially in
      larval-pupal metamorphosis. In the present study, 49 Hsp unigenes were identified
      in the Spodoptera litura transcriptome and their mRNA expression profiles during
      midgut metamorphosis were examined using a tag-based digital gene expression
      system. The genes with the most different levels of expression were then cloned
      and their expression patterns in midguts from sixth instar larvae to pupae were
      analysed using real time quantitative PCR. The responses of these genes to
      juvenile hormone (JH) and 20-hydroxyecdysone (20E) were also studied. The results
      showed that the mRNA levels of 22 Hsp unigenes changed significantly during
      midgut metamorphosis. Amongst these 22 unigenes, hsp70, hsp20.4 and hsp20.8 were
      the most up-regulated members, and hsp15.9, hsp19.3 and hsp22.0 were the most
      down-regulated ones. Further studies showed that hsp70, hsp20.4 and hsp20.8 were
      remarkably up-regulated by JH. In addition, 20E slightly increased the mRNA
      levels of both hsp20.4 and hsp20.8. However, hsp15.9, hsp19.3 and hsp22.0 did not
      respond to either JH or 20E. These results indicate that Hsp70 and small Hsps
      (sHsps) are probably the major players in midgut metamorphosis in S. litura. The
      current findings provide valuable insights into the roles of the Hsp superfamily
      in insect metamorphosis.

PMID- 22957811
TI  - Correlation between perceived asthma control and thoraco-abdominal asynchrony in
      primary care patients diagnosed with asthma.
AB  - OBJECTIVE: Thoraco-abdominal asynchrony (TAA), the discordant movement of the
      abdomen and thorax, may impact upon health-related variables. Here, we
      investigated the extent to which TAA is associated with health-related variables,
      particularly perceived asthma control and quality of life. METHODS: Ambulatory
      respiratory data from 43 patients diagnosed with asthma and 43 healthy age and
      sex-matched controls were recorded over 4 hours. Phase relation (Ph Rel Total),
      the percentage of time that the effects of rib cage (RC) and diaphragmatic
      movement result in opposite effects on intra-thoracic volume, quantified TAA.
      Subjects completed the Mini Asthma Quality of Life Questionnaire (AQLQ), Asthma
      Control Questionnaire (ACQ), Nijmegen questionnaire (NQ), Hospital Anxiety and
      Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI), and
      General Health Perception (GHP) subscale of the short form 36 questionnaire'.
      Capnography profiling, breath-hold time (BHT), and standard spirometry were
      performed. RESULTS: The time in asynchrony was significantly greater in the
      asthma than in the healthy control group (Ph Rel Total = 14% (interquartile range
      (IQR) 8.5-20.7%) versus 10.4% (IQR 7.1-14.5%), p = .012). In patients with
      asthma, Ph Rel Total was weakly associated with poorer ACQ scores (r = 0.33, p =
      .03), and in the healthy control group with GHP (r = 0.319, p = .037). Post-hoc
      exploratory analysis revealed a moderate relationship in the female asthma
      subgroup between Ph Rel Total and AQLQ (r = -0.56, p = .003). CONCLUSIONS: TAA
      may be associated with decreased perceived asthma control. In healthy
      individuals, asynchrony may be associated with low perception of general health.
      Further studies are required to investigate if the reduction of TAA improves
      these health-related variables.

PMID- 22957812
TI  - Relevance of carnosic acid, carnosol, and rosmarinic acid concentrations in the
      in vitro antioxidant and antimicrobial activities of Rosmarinus officinalis (L.)
      methanolic extracts.
AB  - The importance of the diterpenic and rosmarinic acid content in the biological
      activities of rosemary extracts has been studied previously, but how the
      relationship between the concentration of these components affects their
      antioxidant and antibacterial activities has received little attention.
      Accordingly, from a total of 150 plants, 27 methanolic extracts were selected,
      for their similar diterpene contents but different ratios between carnosic acid
      and carnosol concentrations. In extracts with similar rosmarinic acid contents
      but differing proportions between carnosic acid and carnosol, the two diterpenes
      were seen to equally affect the in vitro antioxidant activity; however, and
      related with the antibacterial efficiency, this biological activity improved when
      carnosol was the major diterpene component.

PMID- 22957813
TI  - Work-related factors associated with self-care and psychological health among
      people with type 2 diabetes in Japan.
AB  - This study on individuals with type 2 diabetes living in Japan aimed to examine
      work-related factors that influence self-care and psychological health among
      people. A cross-sectional survey was conducted among 121 working adults with type
      2 diabetes. A self-report questionnaire assessed demographics, work
      characteristics, self-disclosure of diabetes, support in the workplace, work
      related difficulties due to diabetes, and workplace conformity. Dietary self
      care, exercise, depression, and emotional distress were also evaluated. The
      results indicated statistically significant influence of working night shifts,
      self-disclosure of diabetes, and workplace conformity on dietary self-care. Work
      related difficulties due to diabetes had negative effects on depression and
      emotional distress, and job control and support in the workplace were found to be
      correlated with emotional distress. These findings suggest that work-related
      factors have an impact on some forms of self-care activities and psychological
      health and that it is important to increase understanding of these issues and
      provide appropriate support for workers through education and counseling and
      adjustments in the workplace.

PMID- 22957814
TI  - Nuclear receptor coactivator RAC3 inhibits autophagy.
AB  - RAC3 is an oncogene naturally overexpressed in several tumors. Besides its role
      as coactivator, it can exert several protumoral cytoplasmic actions. Autophagy
      was found to act either as a tumor suppressor during the early stages of tumor
      development, or as a protector of the tumor cell in later stages under hypoxic
      conditions. We found that RAC3 overexpression inhibits autophagy when induced by
      starvation or rapamycin and involves RAC3 nuclear translocation-dependent and 
      independent mechanisms. Moreover, hypoxia inhibits the RAC3 gene expression
      leading to the autophagy process, allowing tumor cells to survive until
      angiogenesis occurs. The interplay between RAC3, hypoxia, and autophagy could be
      an important mechanism for tumor progression and a good target for a future
      anticancer therapy.

PMID- 22957815
TI  - The role of clofarabine in acute myeloid leukemia.
AB  - Clofarabine is a second-generation purine nucleoside analog that has been
      synthesized to overcome the limitations and incorporate the best qualities of
      fludarabine and cladribine. Clofarabine acts by inhibiting ribonucleotide
      reductase and DNA polymerase, thereby depleting the amount of intracellular
      deoxynucleoside triphosphates available for DNA replication. Compared to its
      precursors, clofarabine has an increased resistance to deamination and
      phosphorolysis, and hence better stability as well as higher affinity to
      deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside
      phosphorylation. Since the initiation of the first phase I study of clofarabine
      in 1993 in patients with hematologic and solid malignancies, clofarabine has
      demonstrated single-agent antitumor activity in adult acute leukemia, including
      acute myeloid leukemia (AML). Due to its unique properties of biochemical
      modulation when used in combination with other chemotherapy drugs, mainly
      cytarabine, combination regimens containing clofarabine have been evaluated. A
      review of the English literature was performed that included original articles
      and related reviews from the MEDLINE (PubMed) database and from abstracts based
      on the publication of meeting materials. This review describes the development,
      pharmacology and clinical activity of clofarabine, as well as its emerging role
      in the treatment of adult patients with AML and myelodysplastic syndrome.

PMID- 22957816
TI  - Analysis of viable vs. dead Aggregatibacter actinomycetemcomitans and
      Porphyromonas gingivalis using selective quantitative real-time PCR with
      propidium monoazide.
AB  - BACKGROUND AND OBJECTIVES: One of the major disadvantages of DNA-based microbial
      diagnostics is their inability to differentiate DNA between viable and dead
      microorganisms, which could be important when studying etiologically relevant
      pathogens. The aim of this investigation was to optimize a method for the
      selective detection and quantification of only viable Aggregatibacter
      actinomycetemcomitans and Porphyromonas gingivalis cells by combining
      quantitative real-time polymerase chain reaction (qPCR) and propidium monoazide
      (PMA). MATERIAL AND METHODS: Three different concentrations of PMA (10, 50 or 100
      MUm) were added to suspensions of 10(6) (CFU)/mL of viable/dead A.
      actinomycetemcomitans and P. gingivalis cells. After DNA isolation, qPCR was
      carried out using specific primers and probes for the tested bacteria. PMA was
      further tested with different mixtures containing varying ratios of viable and
      dead cells. The efficacy of PMA to detect viable/dead cells was tested by
      analysis of variance. RESULTS: For these specific bacterial pathogens, 100 MUm
      PMA resulted in a significant reduction of qPCR amplification with dead cells
      (10(6) CFU/mL), while with viable cells no significant inhibition was detected.
      PMA was also effective in detecting selectively viable cells by qPCR detection,
      when mixtures of varying ratios of viable and dead bacteria were used.
      CONCLUSIONS: This study demonstrated the efficiency of PMA for differentiating
      viable and dead A. actinomycetemcomitans and P. gingivalis cells. This method of
      PMA-qPCR may be useful for monitoring new antimicrobial strategies and for
      assessing the pathogenic potential of A. actinomycetemcomitans and P. gingivalis
      in different oral conditions when using molecular diagnostic methods.

PMID- 22957817
TI  - Phenylpiperazine derivatives: a patent review (2006 - present).
AB  - INTRODUCTION: The N-phenylpiperazine subunit represents one of the most versatile
      scaffolds used in the medicinal chemistry field. Recently, some N
      phenylpiperazine derivatives have reached late stage clinical trials for the
      treatment of CNS disorders, thus, this is clearly a molecular template that
      already has proven its "druglikeness," However, this scaffold is still strictly
      seen as a "CNS structure" by great part of the scientific community. The aim of
      this review is to draw a contemporary profile of the patents regarding N
      phenylpiperazine derivatives and, them, suggest new research fields to be
      explored. AREAS COVERED: The site of the World Intellectual Property Organization
      (WIPO) was used as the main source in order to perform the research of the
      patents containing N-phenylpiperazine compounds with therapeutic uses. This
      review highlights some examples to show that this heterocyclic moiety can
      successfully yield new classes of hits and prototypes for many other therapeutic
      fields through appropriate substitution of the molecular skeleton. EXPERT
      OPINION: The patent research concerning N-phenylpiperazine derivatives indicated
      for therapeutic uses from 2006 to present date resulted in thirty three
      documents. It is a low number if one considers the several compounds bearing the
      N-phenylpiperazine nucleus that reached the market and/or clinical trials.
      Therefore, this subunit seems to be much underrated at the moment. The adequate
      use of the N-phenylpiperazine moiety, through modulation of its basicity and
      substitution pattern of the aromatic ring, can yield pharmacokinetic and
      pharmacodynamic improvements that are certainly useful in several therapeutic
      areas, thus, being able to diversify the application and utility of this
      scaffold. We expect and strongly suggest the growth of this diversification.

PMID- 22957819
TI  - Diversity among Ralstonia solanacearum strains isolated from the southeastern
      United States.
AB  - This is the first comprehensive study of a collection of Ralstonia solanacearum
      strains from the southeastern United States to be characterized based on biovar,
      pathogenicity, hypersensitive reaction on tobacco, and phylogenetic analyses of
      the egl sequence. Rigorous phylogenetic analysis of the commonly used egl gene
      produced robust phylogenies that differed significantly from a neighbor-joining
      tree differed from and previously published phylogenies for R. solanacearum
      strains. These robust trees placed phylotype IV within the phylotype I clade,
      which may suggest that phylogenies based solely on egl may be misleading. As a
      result of phylogenetic analyses in this study, we determined that U.S. strains
      from Georgia, North Carolina, South Carolina, and older Florida strains isolated
      from solanaceous crops all belong to phylotype II sequevar 7. However, many
      strains recently isolated in Florida from tomato and other crops were more
      diverse than the southeastern United States population. These unique Florida
      strains grouped with strains mostly originating from the Caribbean and Central
      America. One of the exotic strains, which in a previous study was determined to
      be established in northern Florida, was characterized more extensively. Upon
      using Musa-specific multiplex polymerase chain reaction, this strain produced a
      unique banding pattern, which has not previously been reported. Inoculation of
      this strain into Musa spp. did not result in wilt symptoms; however, the plants
      were stunted and root masses were significantly reduced. Furthermore, following
      root inoculation, the bacterium, unlike a typical Florida race 1 biovar 1 strain,
      was recovered from the roots and stems, indicating systemic movement. This is the
      first report of an R. solanacearum strain isolated in the United States that is
      deleterious to the growth of Musa plants.

PMID- 22957818
TI  - Ultrasensitive on-chip immunoassays with a nanoparticle-assembled photonic
      crystal.
AB  - Electrophoretic particle entrapment system (EPES) is employed to generate 2D
      array of nanoparticles coated with biological molecules (i.e., antibodies). Phase
      matching of the excitation and the emission in the 2D arrays with particles
      produces a highly enhanced fluorescence signal that was shown to improve the
      limit of detection in immunoassays. The phase matching is achieved when the
      particle are in the sub-100 nm range. A comparison between different size
      particles shows that the sensitivity of an immunoassay is extended to a range
      that is difficult to achieve with standard technology (e.g., enzyme-linked
      immunosorbent assay-ELISA). The effectiveness of this novel configuration of
      particle-in-a-well was demonstrated with an assay for human epidermal growth
      factor receptor 2 (HER2; breast cancer biomarker), with a detection limit as low
      as 10 attomolar (aM) in less than 10 MUL of serum-based sample. The limit of
      detection of HER2 indicated far superior assay performance compared to the
      corresponding standard 96-well plate-based ELISA. The particle-based photonic
      platform reduces the reagent volume and the time for performing an assay in
      comparison to competing methods. The simplicity of operation and the level of
      sensitivity demonstrated here can be used for rapid and early stage detection of
      biomarkers.

PMID- 22957820
TI  - Development of a variable number of tandem repeats typing scheme for the
      bacterial rice pathogen Xanthomonas oryzae pv. oryzicola.
AB  - Xanthomonas oryzae pv. oryzicola is an important bacterial pathogen responsible
      for outbreaks of bacterial leaf streak (BLS) on rice, mostly occurring in Asia
      and parts of Africa. To better monitor epidemics and assess population
      structures, efficient tools that allow the precise identification and diagnosis
      of pathogenic populations are needed. In this study, we explored variable numbers
      of tandem repeats (VNTR) as a fast, reliable, and cost-effective molecular typing
      tool. Screening of three X. oryzae pv. oryzicola genome sequences (Philippine
      strain BLS256, Chinese strain GX01, and Malian strain MAI10) predicted 28
      candidate VNTR loci. Primer pairs for polymerase chain reaction (PCR)
      amplification of all 28 loci were designed and applied to a panel of 20 X. oryzae
      pv. oryzicola strains originating from Asia and Africa. Sequencing of PCR
      amplicons revealed 25 robust and polymorphic VNTR loci that are shared among
      Asian and African X. oryzae pv. oryzicola strains. A dendrogram constructed from
      25 VNTR loci indicated that most Asian strains are clearly discriminated from
      African strains. However, in agreement with previous reports, one strain from
      Mali is related to Asian strains, pointing to a possible introduction of Asian
      strains to the African continent. The new VNTR-based tool described here is
      useful for studies of population structures and epidemiological monitoring of X.
      oryzae pv. oryzicola.

PMID- 22957821
TI  - Effect of temperature, wetness duration, and planting density on olive
      anthracnose caused by Colletotrichum spp.
AB  - The influence of temperature, wetness duration, and planting density on infection
      of olive fruit by Colletotrichum acutatum and C. simmondsii was examined in
      laboratory and field experiments. Detached olive fruit of 'Arbequina',
      'Hojiblanca', and 'Picual' were inoculated with conidia of several isolates of
      the pathogen and kept at constant temperatures of 5 to 35 degrees C in humid
      chambers. Similarly, potted plants and stem cuttings with fruit were inoculated
      and subjected to wetness periods of 0 to 48 h. Infection occurred at 10 to 25
      degrees C, and disease severity was greater and the mean latent period was
      shorter at 17 to 20 degrees C. Overall, C. acutatum was more virulent than C.
      simmondsii at temperatures <25 degrees C. When temperature was not a limiting
      factor, disease severity increased with the wetness period from 0 to 48 h.
      Disease severity was modeled as a function of temperature and wetness duration;
      two critical fruit incidence thresholds were defined as 5 and 20%, with wetness
      durations of 1.0 and 12.2 h at the optimum temperature. In the field, anthracnose
      epidemics progressed faster in a super-high-density planting (1,904 olive
      trees/ha) than in the high-density plantings (204 to 816 olive trees/ha) and
      caused severe epidemics in the super-high-density planting even with the
      moderately resistant Arbequina. Data in this study will be useful for the
      development of a forecasting system for olive anthracnose epidemics.

PMID- 22957822
TI  - Mummified fruit as a source of inoculum and disease dynamics of olive anthracnose
      caused by Colletotrichum spp.
AB  - Anthracnose, caused by Colletotrichum spp., is a destructive disease of olive
      fruit worldwide. The objective of this study was to investigate the influence of
      agronomical and weather factors on inoculum production using detached olive fruit
      and on the development of epidemics in the field. The pathogen produced very
      large numbers of conidia on rotted (>1.87 * 10(8) conidia/fruit) or mummified
      (>2.16 * 10(4) conidia/fruit) fruit under optimal conditions. On mummified fruit,
      conidial production was highest on mummies incubated at 20 to 25 degrees C and 96
      h of wetness. Repeated washings of mummies reduced conidial production until it
      was very low after five washings. When mummies were placed in the tree canopy,
      conidial production was not reduced after 6 months (May to October); but, when
      they were held on the soil or buried in the soil, conidial production
      comparatively decreased up to 10,000 times. Anthracnose epidemics on susceptible
      'Hojiblanca' and 'Picudo' during three seasons (2005-08) were influenced by
      rainfall, temperature, and fruit ripening, and had three main phases: the latent
      period (May to October); the onset of the epidemic, which coincided with the
      beginning of fruit ripening (early November); and disease development, which was
      predicted by the Weibull model (November to March). No epidemics developed on the
      susceptible cultivars during the driest season (2007-08) or on the resistant
      'Picual' olive during any of the three seasons. These results provide the basis
      for a forecasting system of olive anthracnose which could greatly improve the
      management of this disease.

PMID- 22957823
TI  - Fetal diagnosis of superior vena cava aneurysm.
AB  - Superior vena cava aneurysm is a rare intrathoracic vascular lesion with only 27
      cases reported in the literature. The majority are fusiform and can be associated
      with cystic hygroma due to the close embryonic relationship between lymphatic
      vessels and systemic veins. This is the first report of superior vena cava
      aneurysm diagnosed with fetal echocardiography in a fetus with a cystic hygroma.
      There is a need of a prospective registry to further delineate all aspects of
      this condition and establish the most appropriate therapeutic approach. 

PMID- 22957824
TI  - Dual scale roughness driven perfectly hydrophobic surfaces prepared by
      electrospraying a polymer in good solvent-poor solvent systems.
AB  - We demonstrated a facile method to produce perfectly hydrophobic surfaces
      (advancing and receding angles both 180 degrees ) via electrospraying. When a
      copolymer of styrene and a perfluoroacrylate monomer was electrosprayed in good
      solvents, surfaces composed of micrometer size beads were formed and fairly low
      threshold water sliding angles could be achieved. Addition of high boiling point
      poor solvents to the solutions resulted nanoscale roughness on the beads due to a
      possible phase separation that occurs in a predominantly poor solvent
      environment. However, sliding angles were not zero even on the nanoscale
      roughness dominated topographies achieved by this method. On the other hand, when
      the electrospraying process parameters were set such that micrometer size hills
      of nanoscopically rough beads were formed, 0 degrees  sliding angles were
      measured. Videos of droplets recorded and the adhesive forces measured during a
      contact and release experiment revealed that these dual scale rough surfaces were
      indeed perfectly hydrophobic. Application of the method with other binary good
      solvent-poor solvent systems also resulted in perfect hydrophobicity. Overall
      results showed how the differences in surface topology affected the wettability
      of surfaces within a very narrow range between perfect and extreme hydrophobicity
      (advancing and receding angles both close to 180 degrees ).

PMID- 22957825
TI  - A feasibility study on pinpointing the branches of trigeminal nerve in
      radiofrequency ablation.
AB  - OBJECTIVE: To propose a pinpointing method and to obtain technique parameters for
      puncture of the branches of the trigeminal nerve through anatomical radiological
      study. DESIGN: Trigeminal ganglions and intracranial branches of 25 pieces (50
      sides) of adult skull wet-specimens were dissected and coated with contrast
      agent. X-ray images of the skull in lateral cranial position were collected with
      the tube inclining towards head at 15 degrees , 20 degrees  and 25 degrees .
      'Porus-Clinoid Line' and 'FO-PC axis' were delineated on the images. The latter
      set as the base line, Point A, B and C were settled separately as the upper rim
      of the trigeminal ganglion, the axis of Brach V2 and the junction of the extended
      border lines of Branch V2 and V3 all intersected with it. The collected data was
      processed afterwards. RESULTS: In the cases of 50 sides, the maximum value of the
      'FO-PC Distance' was 17.8 mm; Distance A, 6.6 mm; Distance B, 10.1 mm; and
      Distance C, 6.6 mm, while the minimum of each was 9.4 mm, 0.3 mm, 4.4 mm and 6.6
      mm respectively. Ratios of the 'FO-PC Distance' to Distance B were respectively
      2.00 +/- 0.15 mm, 1.98 +/- 0.15 mm and 1.95 +/- 0.16 mm when tube inclined
      towards head at angles of 15 degrees , 20 degrees  and 25 degrees ; to Distance C
      were 3.06 +/- 0.53 mm, 3.36 +/- 0.60 mm and 3.75 +/- 0.96 mm and to Distance A
      were 10.65 +/- 9.17 mm, 7.33 +/- 5.28 mm, 5.16 +/- 2.30 mm under the same
      condition. CONCLUSION: The results showed that Distances from each branch of
      trigeminal nerve to the medial rim of foramen ovale vary on different individuals
      while the proportional relationship between each branch and 'FO-PC Distance' has
      regularity.

PMID- 22957827
TI  - Electromyographic assessment of jaw muscles in patients with All-on-Four fixed
      implant-supported prostheses.
AB  - This study evaluated the electromyographic (EMG) characteristics of masticatory
      muscles in patients with fixed implant-supported prostheses according to All-on
      Four((r))  principles and in control healthy dentate subjects. Twenty-six
      subjects aged 50-74 years were examined. Eighteen were edentulous and had been
      successfully rehabilitated with (i) mandibular All-on-Four((r))  implant
      supported fixed prostheses and maxillary complete dentures (10 patients) and (ii)
      mandibular and maxillary All-on-Four((r))  implant-supported fixed prostheses
      (eight patients). Eight reference subjects had natural dentition. Surface EMG
      recordings of the masseter and temporalis muscles were performed during maximum
      voluntary teeth clenching and during unilateral gum chewing. All values were
      standardised as percentage of a maximum clenching on cotton rolls. During
      clenching, a good global neuromuscular equilibrium was found in all participants.
      During chewing, all groups had similar values of working-side muscle activities
      and of chewing frequency. No significant differences in the analysed EMG
      parameters were found between the patients with mandibular and maxillary All-on
      Four((r))  implant-supported prostheses and the reference subjects. In contrast,
      standardised pooled muscle activities and standardised muscular activities per
      cycle were larger in patients with a maxillary removable prosthesis than in
      control subjects (Kruskal-Wallis test, P < 0.01). Also, patients wearing a
      complete maxillary denture showed a poor neuromuscular coordination with altered
      muscular pattern and lower values of the index of masticatory symmetry than
      dentate control subjects (P < 0.01). EMG outcomes suggest that All-on-Four((r)) 
      implant-supported prostheses may be considered a functionally efficient treatment
      option for the rehabilitation of edentulous patients with reduced residual bone
      volume.

PMID- 22957826
TI  - Outcome in patients presenting with an aneurysm related intracerebral haemorrhage
      in the post-ISAT era.
AB  - BACKGROUND: The outcome in patients who present with an aneurysm related
      intracerebral haemorrhage (ICH) is poor. There are many treatment strategies now
      available to treat this group of patients. The management approach is dominated
      by a direct surgical approach for both aneurysm treatment and clot evacuation. It
      remains unclear, however, whether overall outcomes justify an aggressive
      treatment approach in this group of patients. We report our results of a
      pragmatic strategy based on availability of expertise and patient condition in
      patients presenting with an aneurysm related intracerebral haemorrhage. METHODS:
      We retrospectively identified and analysed prospectively collected data of SAH
      patients with concurrent ICH. The grade at presentation, treatment decision,
      complications, length of hospital stay, discharge destination, and 6 month
      outcome (Glasgow Outcome Score (GOS) at 6 months) were recorded. FINDINGS:
      Between August 2008 and January 2010, 40 patients (9.2%) with ICH were identified
      from the 433 patients with SAH. Twenty five patients (63%) were transferred
      across to the neurosurgical centre for further investigations and management.
      Most patients presented with poor WFNS grade (61%) and had right sided middle
      cerebral artery aneurysms (58%) with frontotemporal (42%) or temporoparietal
      (42%) haematomas. Management included craniotomy/craniectomy and clipping of the
      aneurysm in 18 patients (72%), coiling followed by surgical clot evacuation in
      five (20%), and craniectomy and coiling (4%) or coiling alone (4%). The outcome
      in treated patients was favourable (GOS 4 or 5) in 46% of patients with a 35%
      overall mortality. CONCLUSION: The presence of an aneurysm related ICH does not
      justify a nihilistic approach, as aggressive treatment is associated with a
      favourable outcome in 46% of patients. In the post-ISAT era, management should be
      patient specific and consideration should be given to both endovascular and open
      surgical therapy.

PMID- 22957828
TI  - Influence of the water content on the diffusion coefficients of Li+ and water
      across naphthalenic based copolyimide cation-exchange membranes.
AB  - The transport of lithium ions in cation-exchange membranes based on sulfonated
      copolyimide membranes is reported. Diffusion coefficients of lithium are
      estimated as a function of the water content in membranes by using pulsed field
      gradient (PFG) NMR and electrical conductivity techniques. It is found that the
      lithium transport slightly decreases with the diminution of water for membranes
      with water content lying in the range 14 < lambda < 26.5, where lambda is the
      number of molecules of water per fixed sulfonate group. For lambda < 14, the
      value of the diffusion coefficient of lithium experiences a sharp decay with the
      reduction of water in the membranes. The dependence of the diffusion of lithium
      on the humidity of the membranes calculated from conductivity data using Nernst
      Planck type equations follows a trend similar to that observed by NMR. The
      possible explanation of the fact that the Haven ratio is higher than the unit is
      discussed. The diffusion of water estimated by (1)H PFG-NMR in membranes
      neutralized with lithium decreases as lambda decreases, but the drop is sharper
      in the region where the decrease of the diffusion of protons of water also
      undergoes considerable reduction. The diffusion of lithium ions computed by full
      molecular dynamics is similar to that estimated by NMR. However, for membranes
      with medium and low concentration of water, steady state conditions are not
      reached in the computations and the diffusion coefficients obtained by MD
      simulation techniques are overestimated. The curves depicting the variation of
      the diffusion coefficient of water estimated by NMR and full dynamics follow
      parallel trends, though the values of the diffusion coefficient in the latter
      case are somewhat higher. The WAXS diffractograms of fully hydrated membranes
      exhibit the ionomer peak at q = 2.8 nm(-1), the peak being shifted to higher q as
      the water content of the membranes decreases. The diffractograms present
      additional peaks at higher q, common to wet and dry membranes, but the peaks are
      better resolved in the wet membranes. The ionomer peak is not detected in the
      diffractograms of dry membranes.

PMID- 22957829
TI  - Should early improvement be re-defined to better predict the maintenance of
      response in first-episode schizophrenia patients?
AB  - OBJECTIVE: To evaluate the predictive validity of early response in first-episode
      schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff
      to the currently proposed early response definition (20% improvement by week 2).
      METHOD: Receiver operator characteristic (ROC) analyses were used to identify the
      predictive validity of the psychopathological improvement of treatment from week
      1 to week 8, regarding the maintenance of response until week 52 as well as to
      define the most reasonable cutoff in 132 first-episode patients. The Youden Index
      (maximum of sensitivity and specificity) was used to compare the newly developed
      and the commonly used early response definition. RESULTS: Starting with week 6, a
      reasonable validity to predict the maintenance of response was found (area under
      the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score
      improvement. Using this cutoff 74 patients (56%) were correctly identified to
      become responder and maintain response during follow-up (sensitivity: 0.747). The
      Youden Index was higher applying the newly developed early response cutoff
      featuring higher specificity compared to the commonly used early response
      definition. CONCLUSION: Regarding long-term treatment, it seems more appropriate
      to base predictions of the patient's maintenance of response not before 6 weeks
      of treatment.

PMID- 22957830
TI  - Influence of gender and stress on the volatile sulfur compounds and stress
      biomarkers production.
AB  - BACKGROUND: Stress and menstrual cycle have been described as factors influencing
      bad breath, as they can alter oral homeostasis and contribute to the production
      of volatile sulfur compounds (VSC). OBJECTIVE: Considering that the
      experimenter's and volunteer's gender may influence the volunteer's responses to
      stress, the aim of this work was to evaluate the influence of stress and gender
      on the production of VSC and salivary biomarkers. METHODS: The experimental acute
      stress was induced by the Video-Recorded Stroop Color-Word Test (VRSCWT). The
      VSC, salivary proteins, and cardiovascular parameters were measured before and
      after VRSCWT. RESULTS: The VRSCWT induced significant increase in total VSC,
      hydrogen sulfide, and blood pressure values in men and women. Women presented
      higher values of both these compounds than men. The increase in systolic blood
      pressure was more pronounced when subjects were evaluated by an experimenter of
      the opposite gender. When women were evaluated by a member of the opposite
      gender, they showed significant increases in salivary alpha-amylase and cortisol
      compared with baseline values. CONCLUSION: Thus, the results showed that VRSCWT
      induced acute stress, which increased VSC production, and these effects were
      shown to be influenced by the gender.

PMID- 22957831
TI  - Temper outbursts in paediatric obsessive-compulsive disorder and their
      association with depressed mood and treatment outcome.
AB  - BACKGROUND: Temper outbursts in youth with obsessive-compulsive disorder (OCD)
      are a common source of concern, but remain poorly understood. This study examined
      a set of hypotheses related to: (a) the prevalence of temper outbursts in
      paediatric OCD, (b) the associations of temper outbursts with OCD severity and
      depressive symptoms; and (c) the influence of temper outbursts on treatment
      response. METHODS: The prevalence of temper outbursts was estimated in a
      specialist OCD clinical sample (n = 387) using parent- and child-report. This was
      replicated in a community sample (n = 18,415). Associations of temper outbursts
      with obsessive-compulsive symptoms and with depressed mood were examined using
      logistic regression models. The influence of temper outbursts on treatment
      response was examined in a subsample of 109 patients treated with cognitive
      behaviour therapy (CBT) with or without medication. RESULTS: Over a third of
      young people with OCD displayed temper outbursts, and rates were similar across
      the clinical and community samples. Temper outbursts were two to three times more
      common in youth with OCD than in healthy controls. However, OCD symptom severity
      was not a strong predictor of child- or parent-reported temper outbursts.
      Instead, both child- and parent- reported temper outbursts were significantly
      associated to depressive symptoms. CBT strongly reduced OCD and depressive
      symptoms, as well as the severity of temper outbursts. There was no significant
      difference in post-treatment OCD or depression scores between those with temper
      outbursts compared to those without. CONCLUSIONS: Temper outbursts are common in
      youth with OCD and are particularly related to depressed mood. They improve with
      CBT for OCD and do not seem to impede OCD treatment response.

PMID- 22957832
TI  - Exome sequencing identifies UPF3B as the causative gene for a Chinese non
      syndrome mental retardation pedigree.
AB  - Mental retardation (MR) is a group of common and complex disabilities affecting
      the central nervous system and appears before the period of brain developmental
      maturity. Recently, only 40% of genetic MR has been identified, however 60%
      remains unexplained. In this study, we applied exome sequencing to identify the
      mutation p.R430X in UPF3B gene in an MR pedigree, which was validated by Sanger
      sequencing and completely cosegregated within this family. UPF3B gene encodes a
      protein involved in nonsense-mediated mRNA decay (NMD). By real-time quantitative
      PCR, we detected the significant difference in the mRNA expression levels of the
      UPF3B and the classical NMD pathway target growth arrest and DNA-damage-inducible
      beta (GADD45B) between the patients and the controls. Our results directly
      implicated that the mutation p.R430X in UPF3B gene was the genetic etiology of
      the MR pedigree.

PMID- 22957833
TI  - Recurrence of cutaneous necrosis in an infant with probable catastrophic
      antiphospholipid syndrome.
AB  - We present the case of a 3-month-old child with probable catastrophic
      antiphospholipid syndrome who, after initial successful management with
      immunomodulary therapies including rituximab, experienced a cutaneous relapse.
      This rare event was successfully re-treated with repeated administration of
      rituximab, supporting its role in the control of this disorder. Dermatologic
      manifestations may be the main clinical presentation of antiphospholipid
      syndrome, a possible underdiagnosed but potentially fatal pathology. 

PMID- 22957834
TI  - Structural basis for the accommodation of bis- and tris-aromatic derivatives in
      vitamin D nuclear receptor.
AB  - Actual use of the active form of vitamin D (calcitriol or 1alpha,25
      dihydroxyvitamin D(3)) to treat hyperproliferative disorders is hampered by
      calcemic effects, hence the continuous development of chemically modified
      analogues with dissociated profiles. Structurally distinct nonsecosteroidal
      analogues have been developed to mimic calcitriol activity profiles with low
      calcium serum levels. Here, we report the crystallographic study of vitamin D
      nuclear receptor (VDR) ligand binding domain in complexes with six
      nonsecosteroidal analogues harboring two or three phenyl rings. These compounds
      induce a stimulated transcription in the nanomolar range, similar to calcitriol.
      Examination of the protein-ligand interactions reveals the mode of binding of
      these nonsecosteroidal compounds and highlights the role of the various chemical
      modifications of the ligands to VDR binding and activity, notably (de)solvation
      effects. The structures with the tris-aromatic ligands exhibit a rearrangement of
      a novel region of the VDR ligand binding pocket, helix H6.

PMID- 22957835
TI  - Unusual case of orbital apex syndrome after chalazion excision.
AB  - Orbital apex syndrome represents a heterogeneous group of disorders. It involves
      damage to the third, fourth and sixth nerves and the ophthalmic division of the
      fifth cranial nerve, and results in optic neuropathy. An 80-year-old man
      presented to our emergency clinic with left acute visual loss and three-day
      history of ocular pain. His medical and ophthalmic history involved diagnosis of
      lung cancer and chalazion excision two weeks prior to presentation. There was
      total left ophthalmoplegia, vision was 'no light perception' and he had a
      relative afferent pupillary defect. An urgent computed tomography scan of the
      orbits showed sub-periosteal abscess on the lateral wall of the orbit extending
      to the optic canal. The muscle cone was unaffected. The diagnosis was orbital
      apex syndrome. He underwent urgent drainage of the abscess and Staphylococcus
      aureus was identified with Gram stain. He was systemically administered
      intravenous antibiotics and steroids. His visual acuity and ophthalmoplegia
      improved rapidly 12 hours after surgery. Prompt diagnosis and treatment in cases
      of orbital apex syndrome, especially in immunocompromised patients, is important
      to prevent visual and life-threatening complications.

PMID- 22957838
TI  - Hole transport enhancing effects of polar solvents on poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonic acid) for organic solar cells.
AB  - This study analyzed the properties of poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) thin-films
      prepared by spin-coating solutions made with the polar solvents methanol,
      acetone, or N,N-dimethylformamide (DMF). A characteristic analysis was carried
      out for poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C(61)-butyric acid methyl
      ester (PCBM)-based organic solar cells (OSCs) having these modified PEDOT:PSS
      thin-films as the hole transport layer. The resistivity of the PEDOT:PSS thin
      film obtained from the DMF solution was 4.89 * 10(-3) Omega.cm with a roughness
      of 3.23 * 10 degrees  nm, compared to 3.51 * 10(-1) Omega.cm and 7.72 * 10(-1) nm
      for a pristine PEDOT:PSS thin-film. The dipole moment increase of the solvent led
      to the decreased resistivity and the increased roughness and transparency of
      PEDOT:PSS thin-films on the structural arrangement of the polymers. Highly
      efficient OSCs with a power conversion efficiency of 3.47% were obtained when DMF
      treated PEDOT:PSS thin-film was used as the hole transport layer.

PMID- 22957836
TI  - Multi-site videoconference tutorials for medical students in Australia.
AB  - BACKGROUND: About two-thirds of medical students are distributed among the major
      metropolitan tertiary teaching hospitals in Queensland, while the remainder are
      sent to regional hospitals up to 500 km away. The aim of this study was to
      investigate the feasibility and effectiveness of conducting surgical tutorials
      via videoconferencing (VC) for medical students undertaking at remote hospitals.
      METHODS: Surgical tutorials were offered to final-year medical students at the
      Royal Children's Hospital (RCH) in Brisbane and shared by VC to students
      undertaking clinical placement at nine remotely located hospitals in Queensland.
      We have conducted a retrospective review of service activity, student
      satisfaction and subject scores from 2008 to 2010. The main outcome measures were
      VC activity, medical students' satisfaction and student exam results pre- and
      post-introduction of the surgical tutorial programme. RESULTS: Between March 2009
      and November 2010, a total of 57 VC tutorials were conducted during nine
      rotations for a total of 669 students. Approximately, 35% of students (236)
      attended tutorials face-to-face at the RCH while the remainder (including those
      at the Mater Children's Hospital in Brisbane and eight regional sites)
      participated via VC. A snapshot survey to measure satisfaction of both groups of
      students showed that overall satisfaction was very high. A total of 299 students
      completed the paediatrics and child health multiple-station assessment task exam
      in 2008, 326 in 2009 and 382 in 2010. The pre-intervention (tutorials not
      delivered by VC) median scores (interquartile range) of surgical and non-surgical
      questions were 5 (4-6) and 23 (21-25). Post-intervention, surgical scores
      increased significantly to 6 (5-7) (P < 0.001), while non-surgical scores
      remained similar at 23 (21-25) (P = 0.64). CONCLUSIONS: Our study demonstrates
      that VC is a feasible and effective method of engaging medical students
      regardless of their location. VC provides equitable access to medical teaching
      for medical students undertaking remote clinical placements.

PMID- 22957839
TI  - Health-related quality of life among Tianjin Chinese patients with type 2
      diabetes: a cross-sectional survey.
AB  - The purpose of this study was to examine factors that influence the quality of
      life among Tianjin Chinese living with type 2 diabetes. In this study, the
      quality of life was assessed in 174 participants. The dependent variables
      included demographic and clinical data, depressive symptoms and lifestyle
      behavioral factors. Chi-square tests and logistic regression analysis were
      conducted to identify significant factors. Using multiple regression analyses,
      the odds ratios (ORs) of having low quality of life were 4.53 (95% confidence
      interval (CI) = 1.89-10.87), 2.83 (95% CI = 1.21-6.63), and 2.48 (95% CI = 1.03
      5.96) for patients with microvascular complications, diabetic neuropathy, and
      peripheral vascular disease, respectively. Coronary heart disease, depression,
      and unhealthy eating habits were also found to have significant negative effects
      on quality of life. In addition, multiple regression analysis showed that regular
      exercise (OR = 0.29, 95% CI = 0.12-0.71) was a protective factor for health
      related quality of life. The identification of these influencing factors will
      assist nurses to provide continuous care to people living with diabetes, thus to
      postpone or avoid complications as well as improve their quality of life.

PMID- 22957840
TI  - Low expression of tissue inhibitor of metalloproteinase-2 may be associated with
      high-risk myelodysplastic syndrome.

PMID- 22957841
TI  - Changes in the polyphenol profile of tomato juices processed by pulsed electric
      fields.
AB  - The effect of pulsed electric fields on the polyphenol profile of tomato juices
      was studied. First, tomatoes were subjected to moderate-intensity pulsed electric
      fields (MIPEFs) and then were immediately refrigerated at 4  degrees C for 24 h.
      Treated and untreated juices were then subjected to high-intensity pulsed
      electric fields (HIPEFs) or thermal treatment (90  degrees C for 60 s). In
      comparison to references, tomatoes subjected to MIPEF treatments led to juices
      with a higher content of polyphenol compounds. A slight decrease in polyphenol
      compounds was observed over time in thermal- and HIPEF-treated juices, with the
      exception of caffeic acid. However, HIPEF-processed tomato juices had a higher
      content of polyphenol compounds (ferulic acid, caffeic-O-glucoside acid, p
      coumaric acid, chlorogenic acid, rutin, and naringenin) just after processing and
      through storage than those thermally treated. Therefore, the combination of
      MIPEFs and HIPEFs could be proposed as a strategy for producing tomato juices
      with a higher content of phenolic compounds.

PMID- 22957842
TI  - Phenylboronic acid-based complex micelles with enhanced glucose-responsiveness at
      physiological pH by complexation with glycopolymer.
AB  - Polymeric nanoparticles with glucose-responsiveness under physiological
      conditions are of great interests in developing drug delivery system for the
      treatment of diabetes. Herein, glucose-responsive complex micelles were prepared
      by self-assembly of a phenylboronic acid-contained block copolymer PEG-b-P(AA-co
      APBA) and a glycopolymer P(AA-co-AGA) based on the covalent complexation between
      phenylboronic acid and glycosyl. The formation of the complex micelles with a
      P(AA-co-APBA)/P(AA-co-AGA) core and a PEG shell was confirmed by HNMR analysis.
      The glucose-responsiveness of the complex micelles was investigated by monitoring
      the light scattering intensity and the fluorescence (ARS) of the micelle
      solutions. The complex micelles displayed an enhanced glucose-responsiveness
      compared to the simple PEG-b-P(AA-co-APBA) micelles and the sensitivity of the
      complex micelles to glucose increased with the decrease of the amount of P(AA-co
      AGA) in the compositions. The cytotoxicity of the polymers and the complex
      micelles was also evaluated by MTT assay. This kind of complex micelles may be an
      excellent candidate for insulin delivery and may find application in the
      treatment of diabetes.

PMID- 22957843
TI  - Highly sensitive and selective chip-based fluorescent sensor for mercuric ion:
      development and comparison of turn-on and turn-off systems.
AB  - Miniaturization is currently an important trend in environmental and food
      monitoring because it holds great promise for on-site monitoring and detection.
      We report here two ready-to-use chip-based fluorescent sensors, compatible with
      microarray technology for reagentless, one-step, fast, highly sensitive and
      selective detection of the mercuric ion (Hg(2+)) in the turn-on and turn-off
      operation modes. Both operation modes are based on the highly selective T-Hg(2+)
      T coordination between two neighboring polythymine (T) strands at a high probe
      density and its induced displacement of the complementary polyadenine strand
      labeled with either fluorophore or quencher, which enables the turn-off and turn
      on detection of Hg(2+), respectively. The turn-off sensor is slightly more
      sensitive than the turn-on sensor, and their detection limits are 3.6 and 8.6 nM,
      respectively, which are both lower than the U.S. Environmental Protection Agency
      limit of [Hg(2+)] for drinkable water (10 nM, 2 ppb). Compared to the turn-off
      sensor with the dynamic Hg(2+) detection range from 3.6 nM to 10 MUM (R(2) =
      0.99), the turn-on sensor has a broader dynamic Hg(2+) detection range, from 8.6
      nM to 100 MUM (R(2) = 0.996). Both sensors exhibited superior selectivity over
      other reported sensors using thymine-rich probes for Hg(2+) detection over other
      common metal ions. In addition, the practical application of the chip-based
      sensors was demonstrated by detecting spiked Hg(2+) in drinking water and fresh
      milk. The sensor has great potential for on-site practical applications due to
      its operational convenience, simplicity, speed, and portability.

PMID- 22957844
TI  - Testin is a tumor suppressor and prognostic marker in breast cancer.
AB  - The testin (TES) gene was previously identified in the fragile chromosomal region
      FRA7G at 7q31.2. In the present study, we aimed to investigate the candidate
      tumor suppressor function of TES and explore its correlations to
      clinicopathologic features and prognosis in breast cancer. In clinical samples,
      we showed that the expression of TES decreased gradually from normal through
      ductal hyperplasia without atypia, atypical ductal hyperplasia, and ductal
      carcinoma in situ, to invasive ductal carcinoma. To explore the possible tumor
      suppressing function of TES, the expression of TES in breast cancer cells was
      manipulated by ectopic expression or by RNAi. We revealed that ectopic TES
      expression significantly inhibited cell proliferation, invasive ability, and
      angiogenesis, whereas knockdown of TES by RNAi enhanced cell proliferation,
      invasive ability, and angiogenesis. In an animal model, TES markedly inhibited
      breast cancer cell xenograft formation in athymic nude mice and reduced breast
      cancer cell metastasis to lung. Moreover, we revealed that TES inhibited the
      invasion and angiogenesis of breast cancer partially through miR-29b-mediated MMP
      2 inhibition. Using the tissue microarray of breast cancer from Yale University,
      we found that lower TES expression was an independent prognostic factor for
      shorter overall survival and disease-free survival with univariate and
      multivariate analyses. Taken together, these data suggest that TES, as a valuable
      marker of breast cancer prognosis, plays an important role in the development and
      progression of breast cancer. TES may be an effective novel target in breast
      cancer prevention and treatment.

PMID- 22957845
TI  - A new manual muscle test for assessing the entire trapezius muscle.
AB  - Manual muscle testing (MMT), the trapezius muscle is an important part of the
      examination in patients with upper extremity dysfunction or pain. PURPOSE: The
      purpose of this study was to assess the reliability and validity of a new MMT
      that assesses the entire trapezius muscle instead of the usual method of
      separating it into three different parts. The new trapezius MMT is similar to the
      serratus anterior muscle test; however, the testing is performed in the frontal
      versus sagittal plane. METHODS: A convenience sample of 11 subjects was recruited
      with no known shoulder pathology. Surface electromyography electrodes were placed
      on the upper, middle, and lower trapezius fibers according to a previously
      validated method and MMTs for the three different trapezius muscle test positions
      were normalized against the new trapezius test position. RESULTS: The new
      trapezius MMT showed very high maximal voluntary isometric contraction (MVIC;
      160.80%) for the upper trapezius muscle, high for the middle trapezius muscle
      (59.23%), and high for the lower trapezius muscle (47.54%) when normalized
      against the MVICs for each individual trapezius muscle tests. CONCLUSIONS: A new
      MMT that assesses the whole trapezius in its role as an upward scapular rotator
      was found to be reliable and valid.

PMID- 22957846
TI  - Unstable sleep and higher sympathetic activity during late-sleep periods of rats:
      implication for late-sleep-related higher cardiovascular events.
AB  - We proposed that the higher incidence of sleep fragmentation, sympathovagal
      imbalance and baroreceptor reflex impairment during quiet sleep may play a
      critical role in late-sleep-related cardiovascular events. Polysomnographic
      recording was performed through wireless transmission using freely moving Wistar
      Kyoto rats over 24 h. The low-frequency power of arterial pressure variability
      was quantified to provide an index of vascular sympathetic activity. Spontaneous
      baroreflex sensitivity was assessed by slope of arterial pressure-RR linear
      regression. As compared with early-light period (Zeitgeber time 0-6 h), rats
      during the late-light period (Zeitgeber time 6-12 h) showed lower accumulated
      quiet sleep time and higher paradoxical sleep time; furthermore, during quiet
      sleep, the rats showed a lower delta% of electroencephalogram, more incidents of
      interruptions, higher sigma% and higher beta% of electroencephalogram, raised low
      frequency power of arterial pressure variability value and lower baroreflex
      sensitivity parameters. During the light period, low-frequency power of arterial
      pressure variability during quiet sleep had a negative correlation with
      accumulated quiet sleep time and delta% of electroencephalogram, while it also
      had a positive correlation with sigma% and beta% of electroencephalogram and
      interruption events. However, late-sleep-related raised sympathetic activity and
      sleep fragmentation diminished when an alpha1-adrenoceptor antagonist was given
      to the rats. Our results suggest that the higher incidence of sleep fragmentation
      and sympathovagal imbalance during quiet sleep may play a critical role in late
      sleep-related cardiovascular events. Such sleep fragmentation is coincident with
      an impairment of baroreflex sensitivity, and is mediated via alpha1
      adernoceptors.

PMID- 22957847
TI  - Cardiac resynchronization therapy as rescue therapy in end-stage heart failure:
      illustration by three-dimensional speckle tracking strain echocardiography.
AB  - We report the case of a 73-year-old man admitted for refractory heart failure
      following implantation of a dual-chamber pacemaker. Three-dimensional (3D)
      echocardiography with speckle tracking area strain identified severe left
      ventricular (LV) dysfunction and LV dyssynchrony following right ventricular
      pacing. As the patient's clinical condition rapidly worsened despite optimal
      medical treatment, a cardiac resynchronization therapy (CRT) pacemaker was
      successfully implanted as rescue therapy. Symptoms rapidly regressed and
      echocardiographic assessment following CRT demonstrated an immediate improvement
      in LV systolic function, confirmed at 9-month follow-up with evidence of reverse
      remodeling. New imaging technologies such as 3D echocardiography with speckle
      tracking area strain may help to identify and follow up patients who will benefit
      from CRT as rescue therapy. 

PMID- 22957848
TI  - Association of urinary bisphenol A concentration with allergic asthma: results
      from the National Health and Nutrition Examination Survey 2005-2006.
AB  - OBJECTIVE: Bisphenol A (BPA) is being increasingly associated with adverse health
      effects. Our objective was to determine whether urinary BPA concentration is
      associated with allergic asthma in a representative US population. METHODS: Data
      for this analysis were obtained from the National Health and Nutrition
      Examination Survey 2005-2006 survey and included asthma-related questions, total
      immunoglobulin E (IgE), 19 allergen-specific IgE levels, and urinary
      environmental phenol measurements. Allergic asthma was defined as a history of
      asthma ever, high eosinophil count, and high total IgE or atopy. Association
      analyses included dichotomous and polychotomous logistic regression, receiver
      operating characteristic curves, Akaike information criterion, and likelihood
      ratio chi(2). RESULTS: We found that 10-fold increase in BPA was independently
      associated with a higher likelihood of allergic asthma in females [odds ratio
      (OR) = 2.21, p = .032] but not in males (OR = 0.83, p = .474). These findings
      were reaffirmed when allergic asthma was defined based on atopy rather than total
      IgE (OR = 2.45, p = .001 in females and OR = 0.83, p = .605 in males). Urinary
      BPA was significantly associated with sensitization to various specific allergens
      in a dose-response manner. Lastly, urinary BPA independently predicted an asthma
      episode in the past 12 months in females but not in males. CONCLUSIONS: Urinary
      BPA is significantly associated with allergic asthma in females.

PMID- 22957850
TI  - Masticatory performance and taste perception in patients submitted to cancer
      treatment.
AB  - The aim of this study was to analyse mastication and the sense of taste in 39
      patients submitted to cancer treatment in different areas of the body and to
      compare these variables with those of 44 control individuals within the same age
      range. The following aspects were assessed: dental status (DMFT); stimulated and
      non-stimulated salivary flow; sense of taste (salty, sweet, bitter and sour); and
      masticatory performance (MP), through the calculation of X(50). Logistic
      regression models were established to test the association between the
      independent variables and cancer treatment. Cancer patients had lesser stimulated
      salivary flow, a smaller number of teeth and occlusal units, worse MP, higher
      salty, sweet and sour taste scores and a lower bitter taste score (P < 0.05). A
      significant positive correlation was found between MP and the DMFT index in both
      groups (P < 0.05), meaning that a lower DMFT index value denoted a smaller X(50)
      value (better masticatory performance). The logistic regression model revealed
      that patients who had undergone cancer treatment had a greater probability of
      exhibiting a smaller number of teeth, higher salty and smaller bitter taste
      scores (P < 0.05). It was concluded that patients who were submitted to cancer
      treatment presented oral physiology alterations when compared with control
      subjects at the same age range.

PMID- 22957849
TI  - Generation of new cytotoxic human ribonuclease variants directed to the nucleus.
AB  - Ribonucleases are promising agents for use in anticancer therapy. Engineering a
      nuclear localization signal into the sequence of the human pancreatic
      ribonuclease has been revealed as a new strategy to endow this enzyme with
      cytotoxic activity against tumor cells. We previously described a cytotoxic human
      pancreatic ribonuclease variant, named PE5, which is able to cleave nuclear RNA,
      inducing the apoptosis of cancer cells and reducing the amount of P-glycoprotein
      in different multidrug-resistant cell lines. These results open the opportunity
      to use this ribonuclease in combination with other chemotherapeutics. In this
      work, we have investigated how to improve the properties of PE5 as an antitumor
      drug candidate. When attempting to develop a recombinant protein as a drug, two
      of the main desirable attributes are minimum immunogenicity and maximum potency.
      The improvements of PE5 have been designed in both senses. First, in order to
      reduce the potential immunogenicity of the protein, we have studied which
      residues mutated on PE5 can be reverted to those of the wild-type human
      pancreatic ribonuclease sequence without affecting its cytotoxicity. Second, we
      have investigated the effect of introducing an additional nuclear localization
      signal at different sites of PE5 in an effort to obtain a more cytotoxic enzyme.
      We show that the nuclear localization signal location is critical for the
      cytotoxicity. One of these variants, named NLSPE5, presents about a 10-fold
      increase in cytotoxicity respective to PE5. This variant induces apoptosis and
      kills the cells using the same mechanism as PE5.

PMID- 22957851
TI  - Preoperative anaemia is common in patients undergoing major gynaecological
      surgery and is associated with a fivefold increased risk of transfusion.
AB  - AIMS: To ascertain the incidence of preoperative anaemia in a cohort of patients
      undergoing major gynaecological surgery in a tertiary Australian hospital over a
      two-year period and to investigate whether it is associated with an increased
      rate of transfusion or complications. METHODS: Using the Western Australian
      Patient Blood Management (PBM) Data System, we obtained data for 843 women
      undergoing major gynaecological surgery over a two-year period at King Edward
      Memorial Hospital, Subiaco, Western Australia. We used regression analysis to
      investigate the relationship between preoperative anaemia, red cell transfusion,
      length of hospital stay and complications. RESULTS: Preoperative anaemia was
      present in 18.1% of women and was associated with a significantly increased risk
      of receiving a red cell transfusion (OR = 5.74, P < 0.001). After adjusting for
      confounders, preoperative anaemia was not independently associated with increased
      complications or hospital length of stay, but receiving a red cell transfusion
      was (P < 0.001). CONCLUSION: This study demonstrates preoperative anaemia is
      common in women undergoing elective major gynaecological surgery and is
      associated with increased red cell transfusions. A system to detect and treat
      anaemia prior to surgery in these patients should be implemented, and
      interventions should be evaluated to ensure they are effective.

PMID- 22957852
TI  - Rituximab use and survival after diffuse large B-cell or follicular lymphoma: a
      population-based study.
AB  - To determine whether reported socioeconomic disparities in survival might be
      related to treatment, we examined patient and tumor characteristics associated
      with receipt of rituximab and survival in the National Cancer Institute's
      Patterns of Care Studies (2003 and 2008) for patients with diffuse large B-cell
      (DLBCL) and follicular (FL) lymphoma. Patients with DLBCL (n = 1192) were less
      likely to receive rituximab if they were older, black or Asian, lacked private
      medical insurance, had impaired performance status, had no lactate dehydrogenase
      measurements or were diagnosed with stage I disease. Patients with FL (n = 476)
      were less likely to receive rituximab if they were unmarried or non-Hispanic
      white. Receipt of rituximab did not differ by neighborhood median income.
      Treatment with rituximab was associated with better survival for patients with
      DLBCL, but not patients with FL. Lower rituximab use in patients with DLBCL
      without private insurance suggests that previously identified socioeconomic
      disparities in survival may, in part, be explained by receipt of rituximab.

PMID- 22957854
TI  - Angiographically "missing" coronary artery: occluded or aberrant?

PMID- 22957853
TI  - Characterization of NODs and TLRs in innate immune response of human cementoblast
      cells.
AB  - OBJECTIVES: Microbial Pattern-recognition receptors (PRRs), such as Toll-like
      receptors (TLRs) and the nucleotide-binding oligomerization domains (NODs), are
      essential for mammalian innate immune response. In this study, we examined the
      characterization of NODs and TLRs on innate immune responses in human
      cementoblast (HCEM) cells. MATERIALS AND METHODS: The gene expression of NODs and
      TLRs was examined by RT-PCR. Interleukin-6 (IL-6) and Interleukin-8 (IL-8)
      productions in culture supernatants were measured by ELISA. Western blot analysis
      was performed to determine the degradation of IkappaB-alpha and Mitogen activated
      protein kinase (MAPK) activation in response to their agonist. RESULTS: The
      levels of NODs and TLRs were apparently expressed in HCEM cells. Although a few
      gene levels were weak in intact cells, the stimulation by their agonists
      increased the gene expression of TLRs. NODs and TLRs led to the production of IL
      6 or IL-8 and the degradation of IkappaB-alpha and MAPK activation in HCEM cells.
      Combination treatment of NOD1 or NOD2 agonists with TLRs agonists did not
      influence the production of IL-6 and IL-8 in HCEM cells. CONCLUSIONS: Our results
      indicate that NODs and TLRs are functionally expressed in HCEM cells and can
      trigger innate immune responses. However, NOD1 and NOD2 may not be cooperated
      with TLRs to elicit an immune response in HCEM cells.

PMID- 22957855
TI  - Catalysis of tRNA aminoacylation: single turnover to steady-state kinetics of
      tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases (aaRS) catalyze the bimolecular association reaction
      between amino acid and tRNA by specifically and unerringly choosing the cognate
      amino acid and tRNA. There are two classes of such synthetases that perform tRNA
      aminoacylation reaction. Interestingly, these two classes of aminoacyl-tRNA
      synthetases differ not only in their structures but they also exhibit remarkably
      distinct kinetics under pre-steady-state condition. The class I synthetases show
      initial burst of product formation followed by a slower steady-state rate. This
      has been argued to represent the influence of slow product release. In contrast,
      there is no burst in the case of class II enzymes. The tight binding of product
      with enzyme for class I enzymes is correlated with the enhancement of rate in
      presence of elongation factor EF-TU. In spite of extensive experimental studies,
      there is no detailed theoretical analysis that can provide a quantitative
      understanding of this important problem. In this article, we present a
      theoretical investigation of enzyme kinetics for both classes of aminoacyl-tRNA
      synthetases. We present an augmented kinetic scheme and then employ the methods
      of time-dependent probability statistics to obtain expressions for the first
      passage time distribution that gives both the time-dependent and the steady-state
      rates. The present study quantitatively explains all the above experimental
      observations. We propose an alternative path way in the case of class II enzymes
      showing the tRNA-dependent amino acid activation and the discrepancy between the
      single-turnover and steady-state rate.

PMID- 22957856
TI  - Improving the solubility of Mn and suppressing the oxygen vacancy density in
      Zn(0.98)Mn(0.02)O nanocrystals via octylamine treatment.
AB  - Zn(0.98)Mn(0.02)O nanocrystals were synthesized by the wet chemical route and
      were treated with different content of octylamine. The environment around Mn and
      the defect type and concentration were characterized by photoluminescence, Raman,
      X-ray photoelectron spectroscopy, and X-ray absorption fine structure. It is
      found that N codoping effectively enhances the solubility of Mn substituting Zn
      via reducing donor binding energy of impurity by the orbital hybridization
      between the N-acceptor and Mn-donor. On the other hand, the O atoms released from
      MnO(6) and the N ions from octylamine occupy the site of oxygen vacancies and
      result in reduction of the concentration of oxygen vacancies in Zn(0.98)Mn(0.02)O
      nanocrystals.

PMID- 22957857
TI  - 5-HT(6) receptor modulators: a patent update. Part 2. Diversity in heterocyclic
      scaffolds.
AB  - INTRODUCTION: Among a variety of proteins included in a relatively wide GPCR
      family, serotonin 5-HT receptors (5-HT(6)Rs) are highly attractive as important
      biological targets with enormous clinical importance. Among this sub-class, 5
      HT(6)R is the most recently discovered group. Available biological data clearly
      indicate that 5-HT(6)R antagonists can be used as effective regulators in a
      variety of contexts, including memory formation, age-related cognitive
      impairments and memory deficits associated with conditions such as schizophrenia,
      Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, this receptor
      has already attracted a considerable attention within the scientific community,
      due to its versatile therapeutic potential. AREAS COVERED: The current paper is
      an update to the comprehensive review article published previously in Expert
      Opinion on Therapeutic Patents [1] Ivashchenko AV, Ivanenkov YA, Tkachenko SE. 5
      Hydroxytryptamine subtype 6 receptor modulators: a patent survey. Expert Opin.
      Ther. Pat, 2010, 20, 1171-1196. Here, the authors mainly focus on small-molecule
      compounds - 5-HT(6) antagonists - which have been described in recent patent
      literature, since the end of 2009. To obtain a clear understanding of the
      situation and dynamic development within the field of 5-HT(6) ligands, having an
      obvious pharmaceutical potential in terms of related patents, the authors provide
      a comprehensive search through several key patent collections. They describe the
      reported heterocyclic compounds with no sulfonyl moiety in sufficient detail to
      provide a valuable insight in the 5-HT(6)R chemistry and pharmacology. Most of
      the described compounds are currently classified as multimodal agents with high
      affinity toward 5-HT(6)R. EXPERT OPINION: Recent progress in the understanding of
      the 5-HT(6) receptor function and structure includes a suggested constitutive
      activity for the receptor, development of a number of multimodal small-molecule
      ligands and re-classification of many selective antagonists as pseudo-selective
      agents. Several heterocylic structures with or without any basic center provide
      sufficient supramolecular interactions and show high agonistic/antagonistic
      activity against 5-HT(6)R. Many 'multitarget' drugs acting, for instance, against
      several isoforms of 5-HTR, including 5-HT(6)R subtype, as well as against
      dopamine and/or histamine receptors were shown to have beneficial therapeutic
      effects. At the same time, these 'unselective' compounds may also increase the
      side-effect potential. The ensemble of antagonistic activity against 5-HT(6)R and
      inhibition potency against BuChE can be regarded as the most promising basis for
      the development of effective drugs with a sufficient therapeutic window for the
      treatment of several neurodegenerative diseases, including AD and PD.

PMID- 22957859
TI  - Efficacy and safety of cross-cylinder photorefractive keratectomy versus single
      method in medium-high astigmatism: a randomized clinical trial.
AB  - BACKGROUND: To compare efficacy and safety of photorefractive keratectomy (PRK)
      by cross-cylinder with single methods in medium-high astigmatism. DESIGN:
      Randomized clinical trial study PARTICIPANTS: Fifty patients with medium-high
      compound myopic astigmatism were enrolled between September 2007 and September
      2008. METHODS: PRK was performed on 100 eyes of 50 patients with compound myopic
      astigmatism. Each patient underwent PRK by cross-cylinder approach in one eye and
      single method on the contralateral eye. Vector analysis was used to assess
      astigmatic results. MAIN OUTCOME MEASURES: Improvement of visual acuity (snelen
      chart), refraction, aberrometry. RESULTS: Uncorrected visual acuity (UCCA) equal
      to 20/40 or better after six months, was achieved in 98% of eyes in the cross
      cylinder method versus 96% in single method.. Mean preoperative spherical
      equivalent(SE) was -5.2 +/-2.1 D in the cross-cylinder method versus -5.1 +/-0.5
      D in the single method. At six months, the mean SE was - 0.5+/-0.4 D and -0.6+/
      0.3 D, respectively. Mean IOS was 0.4+/-0.3 in the cross-cylinder group and 0.4+/
      0.4 in the single group. Mean postoperative absolute change in total root-mean
      square higher order aberrations in the cross-cylinder group and single group were
      0.16 pm and 0.17 pm, respectively. Any of the mentioned differences didn't appear
      to be statistically significant. CONCLUSIONS: Both PRK methods appeared to be
      safe and effective in correcting medium-high astigmatism.

PMID- 22957858
TI  - sarA negatively regulates Staphylococcus epidermidis biofilm formation by
      modulating expression of 1 MDa extracellular matrix binding protein and autolysis
      dependent release of eDNA.
AB  - Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in
      implant-associated infections. Nonetheless, large proportions of invasive
      Staphylococcus epidermidis isolates fail to form a biofilm in vitro. We here
      tested the hypothesis that this apparent paradox is related to the existence of
      superimposed regulatory systems suppressing a multicellular biofilm life style in
      vitro. Transposon mutagenesis of clinical significant but biofilm-negative S.
      epidermidis 1585 was used to isolate a biofilm positive mutant carrying a Tn917
      insertion in sarA, chief regulator of staphylococcal virulence. Genetic analysis
      revealed that inactivation of sarA induced biofilm formation via overexpression
      of the giant 1 MDa extracellular matrix binding protein (Embp), serving as an
      intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA)
      release significantly contributed to biofilm formation in mutant 1585DeltasarA.
      Increased eDNA amounts indirectly resulted from upregulation of metalloprotease
      SepA, leading to boosted processing of autolysin AtlE, in turn inducing augmented
      autolysis and release of eDNA. Hence, this study identifies sarA as a negative
      regulator of Embp- and eDNA-dependent biofilm formation. Given the importance of
      SarA as a positive regulator of polysaccharide mediated cell aggregation, the
      regulator enables S. epidermidis to switch between mechanisms of biofilm
      formation, ensuring S. epidermidis adaptation to hostile environments.

PMID- 22957860
TI  - Cloning of arctic lamprey Lethenteron camtschaticum cd9 with roles in the immune
      response.
AB  - In this study, the cd9 gene, a member of the tetraspanin superfamily and involved
      in various cellular processes, was cloned from Lethenteron camtschaticum. Both
      real-time PCR and immunohistochemical assays showed broad distribution of cd9 in
      various L. camtschaticum tissues. In addition, expression levels of Cd9 mRNA were
      up-regulated in the liver and heart after stimulation by lipopolysaccharide. Flow
      cytometric analyses demonstrated that cd9 was detected on the leukocytes and that
      the expression level was higher on granulocytes than on lymphocytes, which
      implied that cd9 was mainly involved in innate immunity.

PMID- 22957861
TI  - Global major histocompatibility class II beta (mh-IIbeta)-polymorphism in Arctic
      charr Salvelinus alpinus.
AB  - This study explored the use of the gene encoding the beta subunit of the major
      histocompatibility (MH) receptor as a population marker in Arctic charr
      Salvelinus alpinus. The use of this polymorphic marker allowed differentiation of
      the S. alpinus lineages previously defined using mitochondrial DNA (mtDNA) but
      also allowed differentiation between the populations studied within those
      lineages. The majority of the variation observed here occurred prior to the last
      glaciation event. Nevertheless, all S. alpinus populations were differentiated
      using both MH Class II beta (mh-IIbeta) sequences and allelic frequencies. The
      fact that all the populations studied presented high rates of non-synonymous:
      synonymous substitutions and high levels of interpopulation variation, suggested
      mh-IIbeta as an ideal marker to assess differentiation among S. alpinus
      populations in ways that may represent divergence both by genetic drift and
      natural adaptation to the local environment.

PMID- 22957862
TI  - Quantitative and temporal relationships of egg production and sound production by
      black drum Pogonias cromis.
AB  - The timing and levels of black drum Pogonias cromis sound production and egg
      production were compared in an estuarine canal basin of Cape Coral in south-west
      Florida. Surface plankton samples were collected hourly from 1800 to 0400 on two
      consecutive nights while continuous acoustic recordings were made simultaneously
      at five locations in the canal basin. Five pairs of nights were sampled during a
      part of the spawning season from late January to early April 2006. Pogonias
      cromis sound production and egg production occurred on all evenings that samples
      were collected; however, both the timing and levels of sound production were
      negatively associated with those of egg production. Egg production estimates
      ranged from a low of 4.8 eggs m(-3)  in February to a high of 2889.2 eggs m(-3)
      in April. Conversely, maximum nightly sound pressure levels (SPL) ranged from a
      low of 89.5 dB in April to a high of 131.9 dB (re: 1 uPa) in February. The
      temporal centre of sound production was relatively stable among all nights
      sampled but spawning occurred earlier in the day as the season progressed and
      exhibited a strong, positive association with increased water temperature. The
      negative relationship between the levels of sound production and egg production
      was unexpected given the usefulness of sound production as a proxy for
      reproduction on a seasonal basis and may possibly be explained by differences in
      the spawning potential of the female population in the study area on nights
      sampled. Egg mortality rates increased throughout the season and were positively
      associated with densities of hydrozoans and ctenophores.

PMID- 22957863
TI  - First record of the gobiid fish Aulopareia ocellata (Teleostei: Gobiidae) from
      Qeshm Island, The Gulf, with discussion of its generic placement.
AB  - The poorly known gobiid fish species Aulopareia ocellata is recorded for the
      first time from the intertidal zone of north-east Qeshm Island, The Gulf, Iran.
      The species has been referred to previously as Parachaeturichthys ocellatus, but
      here is placed in Aulopareia, pending a revision of the genus. The morphological
      features of A. ocellata are described and compared with congeners and brief
      comparisons of the genera Aulopareia and Parachaeturichthys are provided. A full
      description of the species is given, with illustration of the sensory papillae
      and head-pore pattern. This species has previously been recorded from India
      (Mumbai) and Pakistan (Karachi).

PMID- 22957864
TI  - Effect of ploidy on scale-cover pattern in linear ornamental (koi) common carp
      Cyprinus carpio.
AB  - The effect of ploidy on scale-cover pattern in linear ornamental (koi) common
      carp Cyprinus carpio was investigated. To obtain diploid and triploid linear
      fish, eggs taken from a leather C. carpio female (genotype ssNn) and sperm taken
      from a scaled C. carpio male (genotype SSnn) were used for the production of
      control (no shock) and heat-shocked progeny. In heat-shocked progeny, the 2 min
      heat shock (40 degrees  C) was applied 6 min after insemination. Diploid linear
      fish (genotype SsNn) demonstrated a scale-cover pattern typical for this category
      with one even row of scales along lateral line and few scales located near
      operculum and at bases of fins. The majority (97%) of triploid linear fish
      (genotype SssNnn) exhibited non-typical scale patterns which were characterized
      by the appearance of additional scales on the body. The extent of additional
      scales in triploid linear fish was variable; some fish had large scales, which
      covered almost the entire body. Apparently, the observed difference in scale
      cover pattern between triploid and diploid linear fish was caused by different
      phenotypic expression of gene N/n. Due to incomplete dominance of allele N,
      triploids Nnn demonstrate less profound reduction of scale cover compared with
      diploids Nn.

PMID- 22957865
TI  - Cryptic diversity in the mtDNA of the ornamental fish Carnegiella strigata.
AB  - Mitochondrial DNA ( mtDNA) sequences of the marbled hatchetfish Carnegiella
      strigata, an ornamental fish exported from the Negro River, was examined to
      determine its genetic diversity and population structure in blackwater rivers
      (Negro and Uatuma Rivers) in the central Amazon. Analyses of a 646 bp fragment of
      the ATPase 6/8 mtDNA gene revealed two monophyletic lineages of C. strigata with
      considerable genetic distance between them (10-12%), suggesting that these
      lineages should not be considered a single stock. Furthermore, there were strong
      differences in the geographical distribution of the lineages. These results
      indicate a past association between drainages of the Negro and Uatuma Rivers.
      They also suggest that, in the Negro River, its main tributary, the Branco River,
      may act as a geographical barrier and potentially an ecological barrier between
      populations of the middle and lower portions of the river.

PMID- 22957866
TI  - Comparison of the reproductive ecology of two sympatric blacktip sharks
      (Carcharhinus limbatus and Carcharhinus tilstoni) off north-eastern Australia
      with species identification inferred from vertebral counts.
AB  - Precaudal vertebral counts were used to distinguish between 237 morphologically
      similar Carcharhinus limbatus and Carcharhinus tilstoni and were congruent with
      differences in reproductive ecology between the species. In addition to differing
      lengths at maturity and adult body size, the two species had asynchronous
      parturition, were born at different sizes and the relative frequencies of
      neonates differed in two coastal nursery areas. Despite evidence that
      hybridization can occur, these differences suggest the species are largely
      reproductively isolated.

PMID- 22957867
TI  - Migration timing of female kokanee salmon Oncorhynchus nerka: diel patterns and
      effects of maturation state.
AB  - Diel patterns of migration and migration speed were compared between reproductive
      timing phenotypes in female kokanee salmon Oncorhynchus nerka. Females of varying
      degrees of reproductive maturation were captured on their migration route to the
      Meadow Creek Spawning Channel (British Columbia, Canada), were tagged with
      passive-integrated transponders (PIT tags) and were subsequently monitored with
      stationary receivers. Females showed crepuscular migration timing, with
      approximately equal detections at dawn and dusk. In particular, peaks of movement
      were associated with the appearance of the sun over the mountains in the east and
      the disappearance of the sun over the mountains in the west. Over 25 m, migration
      speed was 1.0 body lengths (measured as fork length; L(F)) s(-1) and did not
      depend on maturation state. Over 3 km, migration speed was much slower (0.2-0.3
      L(F) s(-1)) than over the short distance, with less mature females migrating more
      slowly than more mature females. Less mature females appeared to be in less of a
      hurry to reach breeding areas compared with more mature females.

PMID- 22957868
TI  - An experimental study of the multiple effects of brown trout Salmo trutta on the
      bioenergetics of two Arctic charr Salvelinus alpinus morphs.
AB  - This study investigated the importance of competition with brown trout Salmo
      trutta as a driver of the morphological and behavioural divergence of two morphs
      of Arctic charr Salvelinus alpinus. The morphs originated from two lakes
      differing in absence or presence of the competitor. The bioenergetics and
      behaviour of S. alpinus were quantified in replicate experimental enclosures
      (mean volume: 150 m(3)) stocked with 15 S. alpinus of one morph or the other and
      in the absence or presence of nine S. trutta. The presence of S. trutta decreased
      growth rate, affected food consumption and increased activity costs in S.
      alpinus, but provided little support for the hypothesis that competition with S.
      trutta is a major driver of the divergence of the two S. alpinus morphs. Both
      morphs responded similarly in terms of mean growth and consumption rates per
      enclosure, but the association between individual morphology and growth rate
      reversed between allopatric and sympatric enclosures. While the activity patterns
      of the two morphs were unaffected by the presence of S. trutta, their swimming
      speed and activity rate differed. Since the profound differences in the structure
      of the physical habitat of the source lakes provided a more likely explanation
      for the difference observed among these two morphs than interspecific
      competition, it is hypothesized that physical habitat may sometimes be a
      significant driving force of the phenotypic divergence.

PMID- 22957869
TI  - Age and growth and maturity of southern Africa's largest cyprinid fish, the
      largemouth yellowfish Labeobarbus kimberleyensis.
AB  - The aim of this study was to use specimens of the largemouth yellowfish
      Labeobarbus kimberleyensis, southern Africa's largest cyprinid [IUCN red-listed
      as Near Threatened (NT)], obtained from gillnet by-catch to describe aspects of
      its biology in order to assist future conservation and management decisions.
      Ninety three L. kimberleyensis were collected between March 2007 and May 2008
      from Lake Gariep, South Africa. Labeobarbus kimberleyensis was present in 38% of
      all gillnet catches, but in low numbers (2% of the catch) and it contributed 8%
      to the catch by mass. Age was estimated using astericus otoliths. Growth
      increment formation on these otoliths was validated as annual using edge analysis
      and the mark-recapture of chemically tagged captive fish. Resultant analysis
      showed that the species is slow growing and the oldest aged fish was a 17 year,
      690 mm fork length (L(F)) male. The smallest ripe female fish measured 394 mm
      L(F) and was 7+ years old and the smallest mature male was 337 mm L(F) and 5+
      years old. Slow growth and late maturity make this species vulnerable to
      exploitation emphasizing the need for continued high conservation priority.

PMID- 22957870
TI  - Reproductive biology of cuckoo ray Leucoraja naevus.
AB  - The present study is the first to provide data on the reproductive biology of
      cuckoo ray Leucoraja naevus in Portuguese continental waters. No difference in
      size at maturity was detected between sexes, which was estimated as 56 cm total
      length. Spawning occurs all year round, but maximum activity was during winter
      months. Maximum fecundity is c. 63 eggs female(-1) year(-1). Encapsulated eggs
      are released in batches, nine in total with a mean number of seven extruded eggs
      in each batch.

PMID- 22957871
TI  - Population dynamics and life history of a geographically restricted seahorse,
      Hippocampus whitei.
AB  - The aim of this study was to collect data on population dynamics and life history
      for White's seahorse Hippocampus whitei, a geographically restricted species that
      is listed as data deficient under the IUCN Red List. Data from H. whitei
      populations were collected from two regions, Port Stephens (north) and Sydney
      Harbour (south) in New South Wales, Australia, covering most of the known range
      of H. whitei, from 2005 to 2010. Over 1000 individuals were tagged using
      fluorescent elastomer and on subsequent recaptures were re-measured for growth
      data that were used in a forced Gulland-Holt plot to develop growth parameters
      for use in a specialized von Bertalanffy growth-function model. Growth parameters
      for Port Stephens were: females L(infinity) = 149.2 mm and K = 2.034 per year and
      males L(infinity) = 147.9 mm and K = 2.520 per year compared with estimates from
      Sydney Harbour: females L(infinity) = 139.8 mm and K = 1.285 per year and males
      L(infinity) = 141.6 mm and K = 1.223 per year. Whilst there was no significant
      difference in growth between sexes for each region, H. whitei in Port Stephens
      grew significantly quicker and larger and matured and reproduced at a younger age
      than those from Sydney Harbour. The life span of H. whitei is at least 5 years in
      the wild with six individuals recorded reaching this age. Data collected on
      breeding pairs found that H. whitei displays life-long monogamy with three pairs
      observed remaining pair bonded over three consecutive breeding years. Baseline
      population densities were derived for two Port Stephens' sites (0.035 and 0.110
      m(-2)) and for Manly in Sydney Harbour (1.050 m(-2)). Even though the life
      history parameters of H. whitei suggest it may be reasonably resilient,
      precaution should be taken in its future management as a result of its limited
      geographical distribution and increasing pressures from anthropogenic sources on
      its habitats.

PMID- 22957872
TI  - Reproductive biology of the smooth butterfly ray Gymnura micrura.
AB  - This study provides the first detailed information on the reproductive biology of
      the smooth butterfly ray Gymnura micrura. A total of 905 individuals were
      sampled, 377 of which were used for the reproductive study. Juveniles accounted
      for 75% of the sample, but all life cycle stages were present in the study area.
      The disc width at which 50% were mature (W(D50))was estimated at 269 and 405 mm
      for males and females, respectively. The W(D50V) (based on the onset of
      vitellogenesis) was estimated at 359 mm. Uterine fecundity (mean +/-s.d. = 3.8 +/
      1.3; range: 1-6) was positively correlated with female size. A 3564% gain in
      mean wet mass was observed from egg to full-term embryo in utero. Size at birth
      ranged from 135 to 175 mm W(D) (19.5 to 55.0 g), with a mean of 165.1 mm W(D)
      (43.3 g). The embryo sex ratio was not significantly different from 1:1. The
      ovaries of pregnant females were undergoing vitellogenesis during gestation, with
      females ready to ovulate soon after parturition. Gymnura micrura may have an
      asynchronous reproductive cycle, with females reproducing continuously throughout
      the year.

PMID- 22957873
TI  - Measuring water-borne cortisol in Poecilia latipinna:is the process stressful,
      can stress be minimized and is cortisol correlated with sex steroid release
      rates?
AB  - The stress of water-borne hormone collection process was examined in sailfin
      mollies Poecilia latipinna. Baseline release rates of the stress hormone cortisol
      were measured and minimum confinement time for water sampling was evaluated for a
      standard 60 min v. a 30 min protocol. A 30 min hormone collection period reflects
      release rates over 60 min. Potential stress response to confinement in the beaker
      for the water-borne collection process was tested over 4 days. There was no
      evidence of stress due to the collection methods, as cortisol release rates did
      not differ significantly across four sequential days of handling for P.
      latipinna. Males and females did not differ significantly in baseline cortisol
      release rates. Baseline cortisol release rates from fish immediately after being
      collected in the field were also not significantly different than those in the 4
      day confinement experiment. After exposure to a novel environment, however, P.
      latipinna mounted a stress response. Stress may also affect sex steroids and
      behaviour but cortisol release rates were not significantly correlated with sex
      steroids [11-ketotestosterone (KT), testosterone, or oestradiol], or mating
      attempts. The correlation between water-borne release rates and plasma steroid
      levels was validated for both cortisol and KT. Finally, normalizing cortisol
      release rates using standard length in lieu of mass is viable and accurate. Water
      borne hormone assays are a valuable tool for investigating questions concerning
      the role of hormones in mediating stress responses and reproductive behaviours in
      P. latipinna and other livebearing fishes.

PMID- 22957874
TI  - Symbiosis initiation in the bacterially luminous sea urchin cardinalfish Siphamia
      versicolor.
AB  - To determine how each new generation of the sea urchin cardinalfish Siphamia
      versicolor acquires the symbiotic luminous bacterium Photobacterium
      mandapamensis, and when in its development the S. versicolor initiates the
      symbiosis, procedures were established for rearing S. versicolor larvae in an
      aposymbiotic state. Under the conditions provided, larvae survived and developed
      for 28 days after their release from the mouths of males. Notochord flexion began
      at 8 days post release (dpr). By 28 dpr, squamation was evident and the caudal
      complex was complete. The light organ remained free of bacteria but increased in
      size and complexity during development of the larvae. Thus, aposymbiotic larvae
      of the fish can survive and develop for extended periods, major components of the
      luminescence system develop in the absence of the bacteria and the bacteria are
      not acquired directly from a parent, via the egg or during mouth brooding.
      Presentation of the symbiotic bacteria to aposymbiotic larvae at 8-10 dpr, but
      not earlier, led to initiation of the symbiosis. Upon colonization of the light
      organ, the bacterial population increased rapidly and cells forming the light
      organ chambers exhibited a differentiated appearance. Therefore, the light organ
      apparently first becomes receptive to colonization after 1 week post-release
      development, the symbiosis is initiated by bacteria acquired from the environment
      and bacterial colonization induces morphological changes in the nascent light
      organ. The abilities to culture larvae of S. versicolor for extended periods and
      to initiate the symbiosis in aposymbiotic larvae are key steps in establishing
      the experimental tractability of this highly specific vertebrate and microbe
      mutualism.

PMID- 22957875
TI  - Balancing selection on MHC class I in wild brown trout Salmo trutta.
AB  - Evidence is reported for balancing selection acting on variation at major
      histocompatibility complex (MHC) in wild populations of brown trout Salmo trutta.
      First, variation at an MHC class I (satr-uba)-linked microsatellite locus (mhc1)
      is retained in small S. trutta populations isolated above waterfalls although
      variation is lost at neutral microsatellite markers. Second, populations across
      several catchments are less differentiated at mhc1 than at neutral markers, as
      predicted by theory. The population structure of these fish was also elucidated.

PMID- 22957876
TI  - Reproductive biology of alfonsino Beryx splendens.
AB  - The main aim of this work is to provide a detailed analysis of the reproductive
      cycle of Beryx splendens in the Juan Fernandez Archipelago. The gonadosomatic
      index (I(G)) and maturity ogives in both sexes were estimated using an extensive
      database collected by onboard scientific observers between January 2006 and
      October 2009. A histological analysis of maturation was also completed for
      females collected between May and December 2001. Variations in both I(G) and
      proportion of mature individuals were observed in fish with a fork length (L(F))
      >37 cm for females and >33 cm for males. The main reproductive season was in the
      austral winter and spring (June to November). Fork length at 50% maturity (L(50))
      was estimated as 39.67 cm for females (95% c.i. =39.34, 40.02 cm) and 36.88 cm
      for males (95% c.i. =36.45, 37.36 cm) using macroscopic analysis of gonads.
      Estimates for females using histological data varied slightly with an estimated
      L(50) of 43.67 cm (95% c.i. =42.82, 44.91 cm). Changes in I(G) and maturity were
      modelled as a function of month and L(F) within a generalized additive model
      framework. A high porportion of immature individuals were found throughout the
      year. The results of this study are compared with reproductive traits reported
      for B. splendens in other areas of its distribution and are discussed with
      reference to exploitation, vulnerability and conservation of the B. splendens
      stock in Juan Fernandez Archipelago.

PMID- 22957877
TI  - The effect of dietary lipid content and stress on egg quality in farmed Atlantic
      cod Gadus morhua.
AB  - The present study assessed differences in fecundity and egg quality from Atlantic
      cod Gadus morhua fed isoproteic diets containing 13% fat (low fat, LF) or 20% fat
      (high fat, HF) and either stressed or left unstressed as a control over the
      spawning season. Each diet was fed to triplicate groups of G. morhua from June
      2009, through to first maturation and spawning. In January 2010 sub-groups of G.
      morhua were moved to land-based spawning tanks where the experimental trial was
      carried out. At the start of the experiment, G. morhua fed the high-fat diet were
      significantly larger than G. morhua fed low-fat diet. These differences were
      maintained through the spawning season, although with a loss of mass in both
      dietary groups. Relative fecundity through the season was significantly lower in
      stressed G. morhua fed LF compared to unstressed G. morhua fed the same diet.
      Stressed G. morhua had a higher variability in weekly amount of eggs spawned,
      spawning occurred more irregularly, and the spawning period lasted longer than in
      unstressed G. morhua. Several egg quality variables were also affected: eggs from
      G. morhua fed LF and exposed to stress had lower fertilization and hatching rates
      compared to the unstressed G. morhua fed the same diet as well as all G. morhua
      fed HF. Gadus morhua fed a low-fat diet appeared less tolerant to stress than
      fish fed a high-fat diet.

PMID- 22957878
TI  - The blood chemical status of Atlantic cod Gadus morhua following capture by jig
      and demersal longline with differential hook removal methods.
AB  - Common haematological [haematocrit (Hct)], primary (serum cortisol) and secondary
      (serum glucose and plasma lactate) analytes were utilized to compare blood
      biochemical status of Gadus morhua captured rapidly by jig with that of G. morhua
      captured by commercial demersal longline. In general, the physiological status of
      G. morhua, despite blind hook times, was significantly more disrupted (pronounced
      haemo-concentration and significantly elevated concentrations of cortisol,
      glucose and lactate) following longline capture relative to capture by jig, while
      no differences were detected among longline-caught fish as a function of
      dehooking method (or concomitant extent of overt physical trauma). Blood profiles
      from the more stressed G. morhua, a possible function of more extended longline
      hook times, were similar to the most stressed values reported for this species.
      The results also demonstrate that, although acute blood biochemical status is an
      effective gauge of relative stress, it does not reflect physical injury status,
      which has been shown to exert a strong influence on delayed mortality in previous
      studies in this species. Thus, acute blood chemical status alone may not be the
      most complete predictor of mortality. Future studies should evaluate
      physiological repercussions from capture-handling against physical trauma during
      more extended post-release periods for this species.

PMID- 22957879
TI  - Remarkable karyotypic homogeneity in a widespread tropical fish species:
      Hoplosternum littorale (Siluriformes, Callichthyidae).
AB  - The first chromosomal data in Hoplosternum littorale from an isolated South
      American drainage in north-eastern Brazil are presented. All specimens were
      characterized by a diploid number (2n) of 60 chromosomes divided into three
      metacentric, one submetacentric and 26 acrocentric pairs; single nucleolar
      organizer regions (NOR) on the sixth pair; centromeric and interstitial
      heterochromatin; GC-rich sites on four large acrocentric chromosomes, including
      the NOR-bearing pair, and 5S ribosomal genes at terminal region on short arms of
      two acrocentric pairs. These data are invariably similar to previous reports in
      H. littorale from distant localities throughout South America, which contrasts
      with the chromosomal diversity of Callichthyidae and reinforces the role of human
      activities on the dispersal and colonization of this fish.

PMID- 22957880
TI  - Fourteen new microsatellite markers for Atlantic herring Clupea harengus.
AB  - Fourteen new microsatellite loci were developed and tested on Atlantic herring
      Clupea harengus with 39 individuals from Iceland and 49 individuals from Norway.
      The microsatellites, which contain di, tri and tetranucleotide repeats, are
      polymorphic (7-30 alleles), with observed heterozygosity ranging between 0.69 and
      1.00 and expected heterozygosity between 0.55 and 0.97.

PMID- 22957881
TI  - First record of a whale shark Rhincodon typus in continental Europe.
AB  - A whale shark Rhincodon typus was found in a set-net in southern Portugal in
      October 2011. This was the first record for continental Europe and represents an
      increase of the species' known range. Upwelling events and increase in sea
      surface temperatures are possible reasons for this occurrence.

PMID- 22957882
TI  - Seasonal and ontogenetic diet shift in juvenile stone flounder Platichthys
      bicoloratus.
AB  - The diet of juvenile (0 year old) stone flounder Platichthys bicoloratus after
      settlement was investigated in an estuarine habitat. The principal prey items
      included harpacticoids and palps of polychaetes in February and March and
      thereafter shifted to siphons of the bivalve Nuttallia olivacea from April to
      June. This seasonal change in diet occurred irrespective of body size, suggesting
      that other factors, such as morphological development of the predator or
      vulnerability of prey, induced the diet shift.

PMID- 22957883
TI  - Immersion anaesthesia with tricaine methanesulphonate or propofol on different
      sizes and strains of silver catfish Rhamdia quelen.
AB  - The efficacy of immersion anaesthesia with tricaine methanesulphonate (MS222) or
      propofol on albino and grey silver catfish Rhamdia quelen was assessed through
      induction and recovery times and observation of mortality. Besides reporting a
      novel, efficient and practical use of propofol as an immersion anaesthetic, the
      study shows that it is essential to consider size and strain when anaesthetizing
      R. quelen with MS222 or propofol bath solution in order to minimize physiological
      impact.

PMID- 22957887
TI  - Different approaches to volume assessment of lymph nodes in computer tomography
      scans of head and neck squamous cell carcinoma in comparison with a real gold
      standard.
AB  - BACKGROUND: Volume assessment in head and neck squamous cell carcinoma (HNSCC) is
      becoming a more and more clinical important parameter, especially in treatment
      planning and response control. Various authors showed a significant impact of
      tumour volume on treatment outcome and local control. Regarding the increasing
      impact of induction chemotherapy and primary chemoradiation on HNSCC, the need
      for an adequate measuring tool to judge treatment response becomes obvious. This
      study was performed to compare the momentary 'gold standard', the diameter-based
      approach, and tumour volume assessment in HNSCC with approaches based on
      segmentation algorithms in computer tomography (CT) scans. METHODS: CT scans were
      taken as part of the standardized staging investigations. Using these image data,
      30 lymph nodes were defined and segmented. The segmentations were carried out
      with the newly developed software called 'NeckSegmenter'. After obtaining
      informed consent from the patient, neck dissection was performed and the excised
      lymph nodes underwent analysis of their true volume. The datasets were compared
      with each other and put in correlation with the segmented volumes. RESULTS:
      Pearson's correlation index showed a higher correlation of the segmented volumes
      (r = 0.7979) with the true volumes than the results generated via diameter-based
      equation (r = 0.7974). Furthermore, the diameter-generated volumes show clearly
      too high volumes at 130% (confidence interval: 107.7-156.7%). The volumes
      generated with the segmentation are at 89.18% (confidence interval: 73.52
      108.16%). CONCLUSION: The data show a higher reliability for volumes estimated by
      the segmentation-based approach than the widely used diameter-based approach.

PMID- 22957888
TI  - Kuguaglycoside C, a constituent of Momordica charantia, induces caspase
      independent cell death of neuroblastoma cells.
AB  - Kuguaglycoside C is a triterpene glycoside isolated from the leaves of Momordica
      charantia, and the biological effects of this compound remain almost unknown. We
      investigated the anti-cancer effect of kuguaglycoside C against human
      neuroblastoma IMR-32 cells. In the MTT assay, kuguaglycoside C induced
      significant cytotoxicity against the IMR-32 cells (IC(50) : 12.6 MUM) after 48 h
      treatment. Although examination by Hoechst 33342 staining revealed that
      kuguaglycoside C induced nuclear shrinkage at a high concentration (100 MUM), no
      apoptotic bodies were observed on flow cytometry. No activation of caspase-3 or
      caspase-9 was observed at the effective concentration (30 MUM) of kuguaglycoside
      C. On the other hand, the substance significantly decreased the expression of
      survivin and cleaved poly (ADP-ribose) polymerase (PARP). Kuguaglycoside C also
      significantly increased the expression and cleavage of apoptosis-inducing factor
      (AIF). Moreover, kuguaglycoside C was found to induce caspase-independent DNA
      cleavage in the dual-fluorescence apoptosis detection assay. These results
      suggest that kuguaglycoside C induces caspase-independent cell death, and is
      involved, at least in part, in the mechanism underlying cell necroptosis.

PMID- 22957890
TI  - Modulation in selectivity and allosteric properties of small-molecule ligands for
      CC-chemokine receptors.
AB  - Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by
      metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline
      with similar potencies (EC(50) from 3.9 to 172 MUM). Besides being agonists, they
      acted as selective allosteric enhancers of CCL3. These actions were dependent on
      a conserved glutamic acid at TM-7 (VII:06/7.39). A screening of 20 chelator
      analogues in complex with Zn(II) identified compounds with increased potencies,
      with 7 reaching highest potency at CCR1 (EC(50) of 0.85 MUM), 20 at CCR8 (0.39
      MUM), and 8 at CCR5 (1.0 MUM). Altered selectivity for CCR1 and CCR8 over CCR5
      (11, 12) and a receptor-dependent separation of allosteric from intrinsic
      properties were achieved (20). The pocket similarities of CCR1 and CCR8, contrary
      to CCR5 as proposed by the ligand screen, were elaborated by computational
      modeling. These studies facilitate exploration of chemokine receptors as possible
      targets for therapeutic intervention.

PMID- 22957889
TI  - Specific oral tolerance induction with raw hen's egg in children with very severe
      egg allergy: a randomized controlled trial.
AB  - BACKGROUND: Treatment of severe egg allergy is avoidance of hen's egg (HE) and
      carrying self-injectable epinephrine. Specific oral tolerance induction (SOTI)
      seems a promising alternative treatment. However, some aspects of SOTI are still
      considered experimental. METHODS: We evaluated the efficacy and safety of an
      original 6-month SOTI protocol in children with very severe HE allergy using raw
      HE emulsion. Twenty children (age range: 5-11 yr) were randomized equally into a
      SOTI treatment group and a control group. The treatment group started SOTI and
      underwent a second challenge 6 months later. Control children were kept on an egg
      free diet for 6 months and then underwent a second challenge. RESULTS: After 6
      months, 9/10 children of the SOTI group (90%) achieved partial tolerance (at
      least 10 ml, but <40 ml of raw HE emulsion, in a single dose) and 1 (10%) was
      able to tolerate only 5 ml (no tolerance). After 6 months, nine control children
      tested positive to the second challenge at a dose <=0.9 ml of raw HE emulsion,
      and one reacted to 1.8 ml (SOTI vs. control group p<0.0001). All children in the
      SOTI group had side effects, but no child had a grade 5 reaction according to the
      Sampson grading. CONCLUSION: Six months of SOTI with raw HE emulsion resulted in
      partial tolerance, with regular intake, in a significant percentage of children
      with severe egg allergy.

PMID- 22957891
TI  - Congenital insensitivity to pain with anhidrosis presenting with palmoplantar
      keratoderma.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal
      recessive disease caused by mutations in the NTRK1 gene. The disease is
      characterized by insensitivity to pain and absence of thermal perception. Herein
      a 6-year-old boy is presented with a large ulcer on the sole of his right foot
      and a thick, hyperkeratotic appearance of his palms and soles; there was also a
      medical history of hyperthermia, anhidrosis, recurrent bone fractures,
      osteomyelitis, injuries, mental retardation, dry and exfoliative skin,
      insensitivity to pain, and lack of thermal sensation. Genetic studies revealed a
      homozygote mutation in the NTRK1 gene. Although the patient initially presented
      with palmoplantar keratoderma, genetic studies confirmed the diagnosis of CIPA. 

PMID- 22957892
TI  - Questionnaire-based assessment of owner concerns and doctor responsiveness: 107
      canine chemotherapy patients.
AB  - OBJECTIVE: To quantify owner concerns regarding clinical signs in canine patients
      receiving chemotherapy and to assess degree of concordance between client and
      veterinarian concerns regarding patient quality of life. METHODS: Retrospective
      analysis of owner-reported concerns during chemotherapy treatment. Owner-reported
      adverse events were recorded sequentially for each patient through a partially
      open design questionnaire and correlated with veterinary patient summaries for
      each visit. Canine patients treated for transitional cell carcinoma,
      haemangiosarcoma, malignant melanoma or osteosarcoma were eligible for inclusion.
      Minimum treatment eligibility was two chemotherapy treatments given in 21-day
      protocol cycles, with a maximum of six treatment cycles recorded. RESULTS: A
      total of 553 evaluable visits, seen by 18 oncology clinicians, were assessed.
      Owners expressed concern before chemotherapy in 48% of visits. Owner concerns at
      the first visit did not differ significantly from those expressed at the sixth
      visit. Remission status was a significant factor in owners' rate of reporting
      concerns. Diarrhoea grade was associated with owners' concerns. Clinician gender
      was not associated with responsiveness to owners' concerns. CLINICAL
      SIGNIFICANCE: Questionnaire-based surveys appear to be an effective tool for
      communicating dog owners' concerns regarding chemotherapy and potentially for
      monitoring a clinician's attentiveness. Owners expressed concerns at
      approximately half of chemotherapy appointments.

PMID- 22957894
TI  - Death by mental retardation? The influence of ambiguity on death certificate
      coding error for adults with intellectual disability.
AB  - BACKGROUND: Although the coding of mental retardation as underlying cause of
      death has been recognised by previous researchers as erroneous, factors
      influencing this inaccuracy have not been sufficiently analysed. This study
      explores the effects of diagnostic ambiguity on risk of mental retardation being
      coded as underlying cause of death on US death certificates from 2004. METHODS:
      Utilising all US death certificates from 2004 that included a cause of death code
      for mental retardation, logistic regression analysis provided estimates of the
      likelihood of having mental retardation erroneously coded as the underlying cause
      of death. Estimators used to measure ambiguity included the number of multiple
      causes of death, the place of death, and ICD-10 diagnostic Chapter codes.
      RESULTS: A total of 2278 US death certificates from 2004 included a cause of
      death code for mental retardation. Of these death certificates, 20% erroneously
      coded mental retardation as the underlying cause of death. Reflecting the
      negative impact of diagnostic ambiguity on death certificate coding accuracy,
      mental retardation was more likely to be coded as underlying cause of death for
      decedents who: (1) had a death certificate that provided less information on co
      morbid disease processes; (2) died in an outpatient or emergency room setting; or
      (3) had either abnormal symptomatology or death by injury, accident or other
      external cause. CONCLUSIONS: Findings from this study, as well as prior research,
      demonstrate that attempts to understand mortality trends for this population must
      attend to frequent underlying cause of death coding errors which threaten
      accuracy of cause of death data. Furthermore, inquiry is warranted into the
      impetus behind US death certificate coding policy that continues to allow the
      erroneous coding of 'death by mental retardation'.

PMID- 22957893
TI  - Pou-V factor Oct25 regulates early morphogenesis in Xenopus laevis.
AB  - POU-V class proteins like Oct4 are crucial for keeping cells in an
      undifferentiated state. An Oct4 homologue in Xenopus laevis, Oct25, peaks in
      expression during early gastrulation, when many cells are still uncommitted.
      Nevertheless, extensive morphogenesis is taking place in all germ layers at that
      time. Phenotypical analysis of embryos with Oct25 overexpression revealed
      morphogenesis defects, beginning during early gastrulation and resulting in spina
      bifida-like axial defects. Analysis of marker genes and different morphogenesis
      assays show inhibitory effects on convergence and extension and on mesoderm
      internalization. On a cellular level, cell-cell adhesion is reduced. On a
      molecular level, Oct25 overexpression activates expression of PAPC, a functional
      inhibitor of the cell adhesion molecule EP/C-cadherin. Intriguingly, Oct25
      effects on cell-cell adhesion can be restored by overexpression of EP/C-cadherin
      or by inhibition of the PAPC function. Thus, Oct25 affects morphogenesis via
      activation of PAPC expression and subsequent functional inhibition of EP/C
      cadherin.

PMID- 22957895
TI  - Identification and mode of action of 5-hydroxymethyl-2-furfural (5-hmf) and 1
      methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) as potent
      xanthine oxidase inhibitors in vinegars.
AB  - Vinegars have been used as an alternative remedy for treating gout, but the
      scientific basis remains to be elucidated. In this study, seven commercial
      vinegars and one laboratory-prepared red-koji vinegar were evaluated for the
      inhibitory activity of xanthine oxidase (XO), a critical enzyme catalyzing uric
      acid formation. Red-koji vinegar exhibited potent xanthine oxidase inhibitory
      (XOI) activity and was used for isolating active compounds. The substances under
      two peaks with XOI activity from HPLC were identified as 5-hydroxymethyl-2
      furfural (5-HMF) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid
      (MTCA), by LC-MS-MS and NMR. The XO half-maximal inhibitory concentrations
      (IC(50)) of 5-HMF and MTCA were 168 and 860 MUg/mL, respectively. In further mode
      of-action analysis, the inhibitory mechanism of each compound was elucidated at
      the IC(50) level in the presence of various concentrations of xanthine as the
      substrate. The following Michaelis-Menten kinetics analysis of XO inhibition
      revealed uncompetitive and competitive patterns for 5-HMF and MTCA, respectively.

PMID- 22957896
TI  - Relative distancing: a grounded theory of how learners negotiate the
      interprofessional.
AB  - A number of extant educational, psychological and sociological theories have been
      suggested as possessing utility for interprofessional education (IPE). However,
      there is limited theory proposed that has been derived directly from data. This
      article adds to the theoretical toolkit by theorizing from data using
      constructionist grounded theorizing. This article discusses the grounded
      theorizing of participants' approaches to IPE and describes the social process of
      relative distancing, a collection of strategies employed by participants to
      construct their own professional identities and negotiate their way through
      interprofessional interactions. The categories of relative distancing are
      conceptualized as (1) integrating the professional and the interprofessional; (2)
      constellating and maintaining distance; (3) tensioning and manipulating distance
      and (4) the dimensions of distance. The first, and most theoretically
      integrative, category will be discussed in detail here. It was found that
      participants valued certain learning outcomes over others. They favored learning
      opportunities that were perceived to be of direct relevance to their own
      professional development and contributed finite personal resources to these.
      Resources were committed to those interprofessional learning opportunities where
      relevance was perceived and the conditions of co-presence (with other
      professions) and a context for interaction were achieved. The discussion draws
      links between the data and contemporary discourses of economics and identity.

PMID- 22957897
TI  - Using employee experts to offer an interprofessional diabetes risk reduction
      program to fellow employees.
AB  - A recent increase in the incidence of diabetes and pre-diabetes is causing many
      employers to spend more of their healthcare benefit budgets to manage the
      conditions. A self-insured university in the USA has implemented an
      interprofessional diabetes mellitus risk reduction program using its own employee
      faculty and staff experts to help fellow employees manage their diabetes and pre
      diabetes. The interprofessional team consists of five pharmacists, a dietitian,
      an exercise physiologist, a health educator and a licensed mental health
      practitioner. In addition, the participant's physician serves as a consultant to
      the program, as does a human resources healthcare benefits specialist and a
      wellness coordinator. The volunteer program takes place at the worksite during
      regular business hours and is free of charge to the employees. The faculty and
      staff delivering the program justify the cost of their time through an
      interprofessional educational model that the program will soon provide to
      university students.

PMID- 22957898
TI  - Value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed
      tomography scan versus diagnostic contrast computed tomography in initial staging
      of pediatric patients with lymphoma.
AB  - Our objective was to evaluate the value of (18)F-fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography/computed tomography (PET/CT) versus diagnostic
      contrast CT in the initial staging of pediatric Hodgkin disease (HD) and non
      Hodgkin lymphoma (NHL). Thirty patients with HD and 21 patients with NHL were
      included in this retrospective study. On nodal lesion analysis, PET/CT detected
      94.8% (HD) and 88.3% (NHL) of total lesions, respectively, in contrast to 82.6%
      (HD) and 69.1% (NHL), respectively, for diagnostic contrast CT. PET/CT also
      detected more extranodal lesions. On the patient level, PET/CT detected
      additional lesions in 50% of patients with HD and in 42.9% of patients with NHL.
      In contrast, diagnostic contrast CT detected additional lesions in 16.7% (HD) and
      23.8% (NHL) of total cases. FDG PET/CT led to upstaging in seven cases of HD and
      seven cases of NHL, while diagnostic contrast CT upstaged two cases of NHL. We
      conclude that FDG PET/CT outperforms diagnostic contrast CT in the initial
      staging of pediatric patients with lymphoma.

PMID- 22957900
TI  - Three-dimensional transesophageal echocardiography of aortic atherosclerosis.

PMID- 22957899
TI  - Enhanced and selective killing of chronic myelogenous leukemia cells with an
      engineered BCR-ABL binding protein and imatinib.
AB  - The oncoprotein Bcr-Abl stimulates prosurvival pathways and suppresses apoptosis
      from its exclusively cytoplasmic locale, but when targeted to the mitochondrial
      compartment of leukemia cells, Bcr-Abl was potently cytotoxic. Therefore, we
      designed a protein construct to act as a mitochondrial chaperone to move Bcr-Abl
      to the mitochondria. The chaperone (i.e., the 43.6 kDa intracellular cryptic
      escort (iCE)) contains an EGFP tag and two previously characterized motifs: (1)
      an optimized Bcr-Abl binding motif that interacts with the coiled-coil domain of
      Bcr (ccmut3; 72 residues), and (2) a cryptic mitochondrial targeting signal
      (cMTS; 51 residues) that selectively targets the mitochondria in oxidatively
      stressed cells (i.e., Bcr-Abl positive leukemic cells) via phosphorylation at a
      key residue (T193) by protein kinase C. While the iCE colocalized with Bcr-Abl,
      it did not relocalize to the mitochondria. However, the iCE was selectively toxic
      to Bcr-Abl positive K562 cells as compared to Bcr-Abl negative Cos-7 fibroblasts
      and 1471.1 murine breast cancer cells. The toxicity of the iCE to leukemic cells
      was equivalent to 10 MUM imatinib at 48 h and the iCE combined with imatinib
      potentiated cell death beyond imatinib or the iCE alone. Substitution of either
      the ccmut3 or the cMTS with another Bcr-Abl binding domain (derived from Ras/Rab
      interaction protein 1 (RIN1; 295 residues)) or MTS (i.e., the canonical IMS
      derived from Smac/Diablo; 49 residues) did not match the cytotoxicity of the iCE.
      Additionally, a phosphorylation null mutant of the iCE also abolished the killing
      effect. The mitochondrial toxicity of Bcr-Abl and the iCE in Bcr-Abl positive
      K562 leukemia cells was confirmed by flow cytometric analysis of 7-AAD, TUNEL,
      and annexin-V staining. DNA segmentation and cell viability were assessed by
      microscopy. Subcellular localization of constructs was determined using confocal
      microscopy (including statistical colocalization analysis). Overall, the iCE was
      highly active against K562 leukemia cells and the killing effect was dependent
      upon both the ccmut3 and functional cMTS domains.

PMID- 22957901
TI  - Forty years with a bullet in the myocardium.

PMID- 22957902
TI  - Do all the patients with gastric parietal cell antibodies have pernicious anemia?
AB  - OBJECTIVE: This study evaluated whether all the patients with serum gastric
      parietal cell antibody (GPCA) positivity had pernicious anemia (PA). MATERIALS
      AND METHODS: The blood hemoglobin (Hb), iron, and vitamin B12 concentrations, and
      mean corpuscular volume (MCV) in 124 GPCA-positive patients were measured and
      compared with the corresponding data in 124 age- and sex-matched healthy
      controls. PA was defined by World Health Organization (WHO) as having an Hb
      concentration < 13 g dl(-1) for men and < 12 g dl(-1) for women, an MCV >= 100
      fl, and a serum vitamin B12 level < 200 pg ml(-1) . RESULTS: We found that 20,
      25, and 20 GPCA-positive patients had deficiencies of Hb (men < 13 g dl(-1) ,
      women < 12 g dl(-1) ), iron (<60 MUg dl(-1) ), and vitamin B12 (<200 pg ml(-1) ),
      respectively. Moreover, 16 GPCA-positive patients had abnormally high MCV (>= 100
      fl). GPCA-positive patients had a significantly higher frequency of Hb, iron, or
      vitamin B12 deficiency and of abnormally high MCV (all P-values < 0.001) than
      healthy controls. However, only 12.9% of 124 GPCA-positive patients were
      diagnosed as having PA by the WHO definition. CONCLUSION: Only 12.9% of GPCA
      positive patients are discovered to have PA by the WHO definition.

PMID- 22957903
TI  - Analysis of antibiotic patents issued in China from 1992 to 2011.
AB  - INTRODUCTION: The wide use of antibiotics both within and beyond the medical
      territory plays a significant role in the development of resistant bacteria.
      Therefore, there is a pressing need for the development of effective antibiotics
      worldwide. AREAS COVERED: The current analysis report covers the scientific
      progress in supporting antibiotic patent application and the granted patent
      literature in China for the last 20 years. EXPERT OPINION: Among the 2780 patents
      granted in China last 20 years, beta-lactam antibiotics, macrolides, quinolones,
      aminoglycosides, sulfonamides, glycopeptides and tetracyclines constitute 44.3,
      17.4, 13.5, 4.1, 3.8, 3.0 and 2.1% of total patents, respectively. Scientists
      have faced challenges in developing new antibiotics against increasingly growing
      types of drug-resistant bacteria, which may causes serious global public health
      disaster in future. Poor financial investment in antibiotic research has
      exacerbated the situation. Therefore, new antibiotic patents will be applied
      continuously. The combination individual beta-lactam antibiotics with a beta
      lactamase inhibitor have been demonstrated clinically beneficial and may suggest
      a new way for the development of more effective antibiotics in future. Local
      patent applications of China are stably increasing largely through a dependence
      on the imitation of Western drugs. The current study may help to better
      understand the patent situation in China and to invent the more efficient
      antibiotic therapies.

PMID- 22957904
TI  - Effects of L-dopa and oxazepam on resting-state functional magnetic resonance
      imaging connectivity: a randomized, cross-sectional placebo study.
AB  - Pharmacological functional brain imaging has traditionally focused on
      neuropharmacological modulations of event-related responses. The current study is
      a randomized, cross-sectional resting-state functional magnetic resonance imaging
      study where a single dose of commonly prescribed amounts of either benzodiazepine
      (oxazepam), L-dopa, or placebo was given to 81 healthy subjects. It was
      hypothesized that the connectivity in resting-state networks would be altered,
      and that the strength of connectivity in areas rich in target receptors would be
      particularly affected. Additionally, based on known anxiolytic mechanisms of
      benzodiazepines, modulated amygdala (Am) connectivity was predicted. To test
      this, seed region-based correlational analysis was performed using seven seeds
      placed in well-characterized resting-state networks, in regions with above
      average densities of GABA-A or dopamine receptors and in Am. To alleviate the
      anatomical bias introduced by the a priori selected seed regions, whole-brain
      exploratory analysis of regional homogeneity and fractional amplitude of low
      frequency fluctuations (fALFF) was also carried out. Oxazepam increased
      functional connectivity between midline regions of the default-mode network (DMN)
      and the prefrontal, parietal, and cerebellar areas, but decreased connectivity
      between, for example, the Am and temporal cortex. L-dopa mainly decreased
      connectivity between the Am and bilateral inferior frontal gyri and between
      midline regions of the DMN. The fALFF analysis revealed that L-dopa decreased low
      frequency fluctuations in the cerebellum. It was concluded that the overall
      effects of single administrations of oxazepam and L-dopa on resting-state
      connectivity were small both in strength and in spatial extent, and were on par
      with placebo effects as revealed by comparing the two placebo groups.

PMID- 22957906
TI  - Retracted: Focal adhesions could be cell - cell signaling complexes in
      Myxobacterial swarms.

PMID- 22957907
TI  - Density of states-based design of metal oxide thin-film transistors for high
      mobility and superior photostability.
AB  - A novel method to design metal oxide thin-film transistor (TFT) devices with high
      performance and high photostability for next-generation flat-panel displays is
      reported. Here, we developed bilayer metal oxide TFTs, where the front channel
      consists of indium-zinc-oxide (IZO) and the back channel material on top of it is
      hafnium-indium-zinc-oxide (HIZO). Density-of-states (DOS)-based modeling and
      device simulation were performed in order to determine the optimum thickness
      ratio within the IZO/HIZO stack that results in the best balance between device
      performance and stability. As a result, respective values of 5 and 40 nm for the
      IZO and HIZO layers were determined. The TFT devices that were fabricated
      accordingly exhibited mobility values up to 48 cm(2)/(V s), which is much
      elevated compared to pure HIZO TFTs (~13 cm(2)/(V s)) but comparable to pure IZO
      TFTs (~59 cm(2)/(V s)). Also, the stability of the bilayer device (-1.18 V) was
      significantly enhanced compared to the pure IZO device (-9.08 V). Our methodology
      based on the subgap DOS model and simulation provides an effective way to enhance
      the device stability while retaining a relatively high mobility, which makes the
      corresponding devices suitable for ultradefinition, large-area, and high-frame
      rate display applications.

PMID- 22957905
TI  - Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics
      following a single oral dose.
AB  - AIMS: To determine pharmacokinetic and pharmacogenomic correlates of efavirenz
      central nervous system (CNS) side effects following a single dose. METHODS:
      Thirty-four healthy HIV-negative African Americans were administered a 600 mg
      dose of efavirenz. Blood samples for pharmacokinetics were drawn serially from 0
      to 12 h post-dose. Neuropsychometric testing with drowsiness visual analogue
      scale, grooved pegboard and letter digit substitution tests was done the day
      prior to dosing and at 1, 2, 3, 4 and 6 h post-dose. Subjective CNS symptoms were
      assessed at 6 h post-dose. Composite CYP2B6 516/983 genotype was determined.
      RESULTS: Pharmacokinetic indices reflecting increased plasma efavirenz exposure
      were associated with slower non-dominant hand grooved pegboard task completion
      (Cmax , P1 h  = 0.01, P2 h  = 0.05, P3 h  = 0.03, P4 h  = 0.01; AUC, P1 h  =
      0.04; clearance P1 h  = 0.05, P2 h  = 0.02, P6 h  = 0.01). In a repeated measures
      model analysis that adjusted timing of neuropsychometric testing for timing of
      peak drug concentration, clearance (P < 0.001), AUC(0.312 h) (P = 0.001) and Cmax
      (P = 0.008) were associated with non-dominant grooved pegboard test performance.
      CYP2B6 genotype trended to correlate with non-dominant hand grooved pegboard at 4
      and 6 h (P = 0.07 and 0.06). Decreased drowsiness at 6 h was associated with
      higher Cmax (P = 0.02). CONCLUSIONS: Following a single dose of efavirenz, an
      association between pharmacokinetics and neuropsychometric performance was
      discernable. A weaker association between genotype and neurocognitive test
      performance is likely mediated by effect of genotype on plasma clearance.
      Strategies that lower Cmax during initial dosing may decrease CNS side effects.

PMID- 22957908
TI  - Evaluation of corneal changes with accommodation in young and presbyopic
      populations using Pentacam High Resolution Scheimpflug system.
AB  - BACKGROUND: To evaluate the changes occurring in the cornea with accommodation in
      young and presbyopic people. DESIGN: Prospective study. PARTICIPANTS: Twenty
      three young and 15 presbyopic emmetropic volunteers. METHODS: The Pentacam High
      Resolution system was used to obtain data on the anterior eye segments of
      emmetropic volunteers in unaccommodated (with an accommodation stimulus of 0.0 D)
      and accommodated (with an accommodation stimulus of 5.0 D for the young
      volunteers and 1.0 D for the presbyopic) states. MAIN OUTCOME MEASURES: Anterior
      and posterior corneal axial curvature, corneal volume, corneal aberration,
      anterior chamber depth and anterior chamber volume were evaluated. RESULTS: A
      significant decline in anterior chamber depth and anterior chamber volume was
      induced by accommodation in both young and presbyopic volunteers. There was a
      small but statistically significant change in corneal volume within 3.0, 5.0 and
      7.0 mm diameters during accommodation in both groups. The changes in the corneal
      curvature map were significant with accommodation in both groups, although
      individual variations were found in anterior and posterior corneal axial
      curvature. Moreover, the decreased higher order aberrations were found in both
      anterior and entire cornea. In particular, spherical aberration was changed in
      the young group with 5.0 D accommodation stimulus. CONCLUSION: This study showed
      that accommodation can influence the corneal shape and curvature, and,
      especially, decreased corneal high-order aberrations. Although the modification
      in corneal shape was small, it produced variations in higher order aberrations
      with accommodation that may be beneficial for visual performance in near vision.

PMID- 22957909
TI  - Inclusion complexes between amphiphilic phenyleneethynylene fluorophores and
      cyclodextrins in aqueous media.
AB  - Binding events of cyclodextrins (CyD's) in aqueous media are important for
      designing and explaining the host-guest chemistry applied in sensing and
      controlled release systems. A water-soluble tricationic compound (3N(+)) with
      three branches of phenyleneethynylene fluorescent moieties and its related
      amphiphilic compounds (3C(-), N(0)N(+), N(+), and 2N(+)) are employed as
      molecular probes in the systematic characterization of the supramolecular
      interactions with CyD's (alpha, beta, and gamma). The strong fluorescence
      enhancement, combined with induced circular dichroism (CD) signals and (1)H NMR
      data, is evidence of 1:1 static inclusion complexes of 3N(+)/gamma-CyD and
      2N(+)/gamma-CyD. 3N(+) presents a structural design which can form inclusion
      complexation with gamma-CyD with one of the highest binding constants of 3.0 *
      10(4). The relatively moderate fluorescence enhancement, shift of (1)H NMR
      signals, and weak induced CD signals indicate fast exchange complexation of beta
      CyD with the amphiphilic guest molecules. The interaction with alpha-CyD is
      perceived only for N(0)N(+), the only nonbranched fluorescent guest model, via
      its strong fluorescence enhancement. However, the lack of (1)H NMR signal
      splitting and the lack of induced CD signals suggest the noninclusion mode of
      binding between N(0)N(+) and alpha-CyD.

PMID- 22957910
TI  - Dichotomies and differences: challenges for mental health nursing.

PMID- 22957911
TI  - Short implants with a nanometer-sized CaP surface provided with either a platform
      switched or platform-matched abutment connection in the posterior region: a
      randomized clinical trial.
AB  - OBJECTIVE: To assess the performance of short nanorough implants (8.5 mm in
      length) provided with either a platform-matched or a platform-switched implant
      abutment connection, placed in the resorbed posterior region of partially dentate
      patients. MATERIALS AND METHODS: A total of 149 implants with a dual-acid surface
      and a discrete crystalline deposition of nanometer-sized CaP particles, with
      either a platform-matched (control) or a platform-switched implant-abutment
      connection (test) were placed (randomly assigned) in 92 patients. Follow-up
      visits were conducted 1 month and 1 year after placing the implant crown. Outcome
      measures were implant survival, radiographic peri-implant bone loss, clinical
      parameters, and patient's satisfaction. RESULTS: One year after loading, 6 of 76
      implants in the control group (survival 92.1%) and 3 of 73 implants in the test
      group (survival 95.9%) were lost (P = 0.33). Radiographic bone loss around test
      implants (0.50 +/- 0.53 mm) was significantly less than around control implants
      (0.74 +/- 0.61 mm; P < 0.005). With regard to implant survival, clinical
      parameters, and patient's satisfaction, no significant differences were observed
      between test and control group. CONCLUSIONS: For teeth replacements in the
      resorbed posterior region of partially dentate patients, short implants with a
      platform-switched implant-abutment connection showed significantly less peri
      implant bone loss after 1 year in function, while implant survival, clinical
      parameters, and patient's satisfaction were independent of the implant-abutment
      connection design.

PMID- 22957912
TI  - Grapefruit (Citrus paradisi Macfad) phytochemicals composition is modulated by
      household processing techniques.
AB  - Grapefruits (Citrus paradisi Macfad) contain several phytochemicals known to have
      health maintaining properties. Due to the consumer's interest in obtaining high
      levels of these phytochemicals, it is important to understand the changes in
      their levels by common household processing techniques. Therefore, mature Texas
      "Rio Red" grapefruits were processed by some of the common household processing
      practices such as blending, juicing, and hand squeezing techniques and analyzed
      for their phytochemical content by high performance liquid chromatography (HPLC).
      Results suggest that grapefruit juice processed by blending had significantly (P
      < 0.05) higher levels of flavonoids (narirutin, naringin, hesperidin,
      neohesperidin, didymin, and poncirin) and limonin compared to juicing and hand
      squeezing. No significant variation in their content was noticed in the juice
      processed by juicing and hand squeezing. Ascorbic acid and citric acid were
      significantly (P < 0.05) higher in juice processed by juicing and blending,
      respectively. Furthermore, hand squeezed fruit juice had significantly higher
      contents of dihydroxybergamottin (DHB) than juice processed by juicing and
      blending. Bergamottin and 5-methoxy-7 gernoxycoumarin (5-M-7-GC) were
      significantly higher in blended juice compared to juicing and hand squeezing.
      Therefore, consuming grapefruit juice processed by blending may provide higher
      levels of health beneficial phytochemicals such as naringin, narirutin, and
      poncirin. In contrast, juice processed by hand squeezing and juicing provides
      lower levels of limonin, bergamottin, and 5-M-7-GC. These results suggest that,
      processing techniques significantly influence the levels of phytochemicals and
      blending is a better technique for obtaining higher levels of health beneficial
      phytochemicals from grapefruits. Practical Application:  Blending, squeezing, and
      juicing are common household processing techniques used for obtaining fresh
      grapefruit juice. Understanding the levels of health beneficial phytochemicals
      present in the juice processed by these techniques would enable the consumers to
      make a better choice to obtain high level of these compounds.

PMID- 22957915
TI  - Consumer awareness of salt and sodium reduction and sodium labeling.
AB  - Reduction of dietary sodium by reduction of sodium in foods is a current industry
      target. Quantitative information on consumer knowledge of sodium and reduction of
      dietary sodium is limited. The objectives of this study were to characterize
      consumer knowledge and awareness of sodium and salt reduction in foods. Consumers
      (n = 489) participated in a quantitative internet survey designed to gather
      knowledge and attitudes towards dietary sodium, sodium in foods, and health.
      Eating habits and food consumption characteristics, knowledge of salt and sodium,
      and interest in health and wellness were probed. Saltiness believe and sodium
      knowledge indices were calculated based on correct responses to salt levels in
      food products. Kano analysis was conducted to determine the role of nutrition
      labels and satisfaction/dissatisfaction of foods. Consumers were aware of the
      presence of sodium in "salty" foods, and that sodium was part of salt. People who
      had a family history of certain diseases associated with a higher intake of
      dietary sodium did not necessarily have more knowledge of the relationship
      between sodium intake and a specific disease compared to consumers with no family
      history. Sodium content on the food label panel did not influence consumer
      dissatisfaction; however, sodium content did not necessarily increase consumer
      product satisfaction either. The addition of a healthy nutrient (that is, whole
      grain, fiber) into a current food product was appealing to consumers. For
      nutrient labeling, a "reduced" claim was more appealing to consumers than a
      "free" claim for "unhealthy" nutrients such as fat, sodium, and sugar. PRACTICAL
      APPLICATION: This study demonstrated the current state of consumer knowledge on
      sodium and salt reduction, and consumer perception of the relationship between
      diets high in sodium and many chronic diseases. Information that may contribute
      to consumer satisfaction on nutrition panel labeling was also determined.

PMID- 22957916
TI  - Oxidative stability and consumer acceptance of fish oil fortified nutrition bars.
AB  - Oat and soy-based nutrition bars were fortified with 4 levels of fish oil (0, 6,
      12, or 18 g per approximately 600 g batch), representing 0%, 20%, 40%, or 60%
      replacement of canola oil. The commercially available purified fish oil was not
      emulsified nor encapsulated, and contained tocopherols. Baked nutrition bars were
      evaluated for proximate composition, water activity, alpha-linolenic acid (ALA),
      eicosapentaenoic acid (EPA), and docosahexaenoic (DHA) content, and consumer
      acceptance using a 9-point hedonic scale. The bars were sealed in opaque bags and
      stored in a stability chamber at 25  degrees C and 50% relative humidity for 10
      wk to assess oxidative stability. There were no significant (P > 0.05)
      differences in proximate composition, water activity, or ALA levels among
      treatments. EPA and DHA levels were significantly (P < 0.05) different among
      treatments, averaging 178.1 mg/serving (20-FO), 488.3 mg/serving (40-FO), and
      664.6 mg/serving (60-FO), but none changed during storage. Headspace hexanal and
      propanal levels decreased over time but were not significantly different among
      treatments until week 10. Peroxide values were not significantly different except
      between the control and 60-FO bars. Low values obtained for these analyses
      suggest negligible oxidation in the bars. Consumer acceptance scores did not
      differ significantly between the control and lowest fortification level (20-FO),
      ranging from 6.4 to 6.6 for aroma, texture, flavor, and overall acceptability.
      These results suggest that nonemulsified, nonencapsulated fish oil can
      successfully replace canola oil in intermediate moisture nutrition bars to
      provide EPA and DHA levels as high as 178 mg/serving without affecting consumer
      acceptability or oxidative stability. PRACTICAL APPLICATION: Omega-3 fatty acid
      rich fish oil has been shown to have numerous health benefits, but there are
      limitations to its use in shelf-stable food products. In this study, nutrition
      bars were successfully fortified with nonencapsulated, nonemulsified fish oil to
      deliver 178 mg EPA and DHA per 35 g serving. The fortified bars were oxidatively
      stable over 10 wk and acceptable to consumers.

PMID- 22957917
TI  - Owen Fennema, renaissance man 1929-2012.

PMID- 22957919
TI  - Expression and roles of Wilms' tumor 1-associating protein in glioblastoma.
AB  - Glioblastoma is a diffusely growing malignant brain tumor and among the most
      aggressive of all tumors. Wilms' tumor 1-associating protein (WTAP) is a nuclear
      protein that has been associated with regulation of proliferation and apoptosis.
      Although its dynamic expression and physiological functions in vascular cells
      have been reported, those in other cells are largely unknown. Here, we show for
      the first time that WTAP is overexpressed in glioblastoma. Moreover we found that
      WTAP regulates migration and invasion of glioblatoma cells. Specific knockdown by
      siRNA or overexpression by cDNA regulated migration and invasion of cancer cells.
      In xenograft study, WTAP overexpression made cancer cells more tumorigenic. In
      the investigation for its underlying mechanism, we found that the activity of
      epidermal growth factor receptor can be regulated by WTAP. These results reveal a
      novel function of WTAP and suggest its clinical application.

PMID- 22957920
TI  - Disclosing the origin and diversity of Omani cattle.
AB  - Among all livestock species, cattle have a prominent status as they have
      contributed greatly to the economy, nutrition and culture from the beginning of
      farming societies until the present time. The origins and diversity of local
      cattle breeds have been widely assessed. However, there are still some regions
      for which very little of their local genetic resources is known. The present work
      aimed to estimate the genetic diversity and the origins of Omani cattle. Located
      in the south-eastern corner of the Arabian Peninsula, close to the Near East,
      East Africa and the Indian subcontinent, the Sultanate of Oman occupies a key
      position, which may enable understanding cattle dispersal around the Indian
      Ocean. To disclose the origin of this cattle population, we used a set of 11
      polymorphic microsatellites and 113 samples representing the European, African
      and Indian ancestry to compare with cattle from Oman. This study found a very
      heterogenic population with a markedly Bos indicus ancestry and with some degree
      of admixture with Bos taurus of African and Near East origin.

PMID- 22957921
TI  - Cell cycle regulation in mouse heart during embryonic and postnatal stages.
AB  - The regulation of cardiomyocyte proliferation is important for heart development
      and function. Proliferation levels of mouse cardiomyocytes are high during early
      embryogenesis and start to decrease at midgestation. Many cardiomyocytes undergo
      mitosis without cytokinesis, resulting in binucleated cardiomyocytes during early
      postnatal stages, following which the cell cycle arrests irreversibly. It remains
      unknown how the proliferation pattern is regulated, and how the irreversible cell
      cycle arrest occurs. To clarify the mechanisms, fundamental information about
      cell cycle regulators in cardiomyocytes and cell cycle patterns during embryonic
      and postnatal stages is necessary. Here, we show that the expression, complex
      formation, and activity of main cyclins and cyclin-dependent kinases (CDKs)
      changed in a synchronous manner during embryonic and postnatal stages. These
      levels decreased from midgestation to birth, and then showed one wave in which
      the peak was around postnatal day 5. Detailed analysis of the complexes suggested
      that CDK activities were inhibited before the protein levels decreased. Analysis
      of DNA content distribution patterns in mono- and binucleated cardiomyocytes
      after birth revealed changes in cell cycle distribution patterns and the
      transition from mono- to binucleated cells. These analyses indicated that the
      wave of cell cycle regulator expression or activities during postnatal stages
      mainly produced binucleated cells from mononucleated cells. The data obtained
      should provide a basis for the analysis of cell cycle regulation in
      cardiomyocytes during embryonic and postnatal stages.

PMID- 22957922
TI  - Response to the letter to the editor.

PMID- 22957923
TI  - The effect of Pro(2) modifications on the structural and pharmacological
      properties of endomorphin-2.
AB  - Endomorphins (EM-1 and EM-2) are selective, high affinity agonists of the MU
      opioid (MOP) receptor, an important target in pain regulation. Their clinical use
      is impeded by their poor metabolic stability and limited entry to the central
      nervous system. In this study, the Pro(2) residue of EM-2 was modified
      systematically through substitution by hydroxyproline (Hyp), (S)-beta-homoproline
      (betaPro), 2-aminocyclopentene-1-carboxylic acid (DeltaAcpc), or 2
      aminocyclohexene-1-carboxylic acid (DeltaAchc) to obtain stable MOP active
      compounds. Both Hyp(2) and betaPro(2) substitution decreased receptor affinity.
      Analogues incorporating alicyclic beta-amino acids exhibited diverse receptor
      binding properties, depending on the configuration of the substituent side-chain.
      (1S,2R)DeltaAcpc(2)-EM-2 was shown to have MOP affinity and selectivity
      comparable to those of EM-2 and proved to act as agonist while being resistant to
      proteolysis. NMR and molecular dynamics (MD) studies revealed that bent backbone
      structures are predominant in the most potent analogues, while their presence is
      less pronounced in ligands of lower receptor affinity.

PMID- 22957924
TI  - Laparoscopic resection of gastrointestinal stromal tumors: safe, efficient, and
      comparable oncologic outcomes.
AB  - BACKGROUND: Surgery of gastrointestinal stromal tumors (GISTs) has been modified,
      and laparoscopic resection of GIST has gained improvement and roles. PATIENTS AND
      METHODS: We retrospectively reviewed clinical data and oncological outcomes of
      our GIST patients who underwent laparoscopic surgery and traditional open
      surgery. In total, 227 pathologically diagnosed GIST cases were retrospectively
      reviewed in Chang Gung Memorial Hospital at Linkou, Taipei, Taiwan, between 2005
      and 2010. We excluded those with tumor size >5 cm, biopsy-only, combined other
      operation, endoscopic mucosal resection, tumor located in the duodenum, colon
      rectum, esophagocardiac junction, omentum, pelvic area, or retroperitoneum, or
      metastasis when operated on and those diagnosed as other disease after
      immunohistologic examination of GIST. Fifty-eight cases were enrolled, including
      16 patients in the laparoscopic surgery group (LSG) and 42 patients in the open
      surgery group (OSG). The patients' demography, perioperative, pathologic result,
      and oncology result were recorded and analyzed. RESULTS: Both groups showed no
      difference in clinical demography, tumor size, and locations. LSG patients showed
      fewer days to resume diet, shorter postoperative hospital stays, and less use of
      patient-controlled analgesia. The postoperative morbidity in LSG and OSG was 6.3%
      and 19%, respectively. The median follow-up time was 32.73 months in LSG and
      39.75 months in OSG. Recurrence or metastasis was observed in 3 patients (1 in
      LSG and 2 in OSG). The recurrence rate between LSG and OSG showed no significant
      difference. CONCLUSIONS: Laparoscopic surgery was technically feasible for GIST
      of no more than 5 cm located at the stomach and small bowel. In the current
      study, we demonstrated that LSG patients benefited from fewer days to resume diet
      (5 versus 5.71 days), shorter postoperative stays (8 versus 9.07 days), and less
      patient-controlled analgesia use (6.7% versus 90.9%) during the perioperative
      period with the same short-term oncology result compared with OSG patients.

PMID- 22957925
TI  - Intraoperative endoscopist-controlled guide wire cannulation technique
      sphincterotomy during laparoscopic cholecystectomy.
AB  - BACKGROUND: Intraoperative endoscopic sphincterotomy (IOES) is considered
      superior to preoperative endoscopic sphincterotomy and other treatment modalities
      for management of common bile duct (CBD) stones. Here we describe the method and
      results of our technique of IOES in the supine position during laparoscopic
      cholecystectomy (LC) using a guide wire cannulation (intraoperative supine
      endoscopic sphincterotomy by endoscopist-controlled guide wire cannulation)
      [ISEEG] technique). PATIENTS AND METHODS: This is a retrospective analysis of the
      outcome for 36 patients undergoing LC with IOES (ISEEG technique) for acute
      biliary colic and jaundice with suspicion of choledocholithiasis. RESULTS: On
      confirmation of CBD stones by intraoperative cholangiogram, CBD catheterization
      was successful in 34/36 (94.44%) patients with successful stone clearance in all
      of them by the ISEEG technique demonstrating 100% efficacy for stone clearance;
      the remaining 2 patients needed conversion to open surgery. The median time for
      the ISEEG technique during intraoperative sphincterotomy was 9 minutes (range, 7
      23 minutes). Average hospital stay was 4.8 days (range, 2-15 days). At the 1
      month follow-up, all patients were biliary symptom-free. Three of 36 patients
      (8.33%) had mild postoperative pancreatitis. There was no procedure-related
      mortality. CONCLUSIONS: LC coupled with the ISEEG technique performed by an
      expert endoscopist is an effective single-stage minimally invasive treatment for
      CBD stones with good efficacy, good stone clearance rates, and low morbidity.

PMID- 22957926
TI  - Radiographic kidney measurements in North American pet ferrets (Mustela furo).
AB  - OBJECTIVES: The purpose of the current study was to determine normal radiographic
      kidney -measurements in pet ferrets. METHODS: Kidney length and width dimensions
      and the length of the second lumbar vertebra (L2) were determined from survey
      ventrodorsal radiographs in 53 neutered ferrets of various ages, weight and sex,
      with no evidence of urogenital disease. Kidney dimensions were expressed as a
      ratio to the body length of L2. RESULTS: All ferrets in this study had six lumbar
      vertebrae. The median length of L2 was 13.3 mm, and was longer in males than
      females (P=0.0001). The 95% confidence interval for kidney-length-to-L2 ratios
      was 2.21 to 2.31 for the right and 2.15 to 2.25 for the left. For the kidney
      width-to-L2 ratios these intervals were 1.09 to 1.14 for the right and 1.07 to
      1.12 for the left kidney. There was a significant association between kidney size
      and weight or sex but not with age. CLINICAL SIGNIFICANCE: The results of this
      radiographic study may allow practitioners to have a more -objective clinical
      radiographic evaluation of kidney size of pet ferrets based on individual traits.

PMID- 22957927
TI  - Multifocal childhood cutaneous tuberculosis: report of two interesting cases from
      Sikkim, India.
AB  - Cutaneous tuberculosis is an important health problem in developing countries
      such as India. Poverty, overcrowding, malnutrition, and ignorance are
      predisposing factors. The commonly seen variants of cutaneous tuberculosis are
      scrofuloderma, lupus vulgaris, and tuberculosis verrucosa cutis. Malnourished
      children may present with unusual forms of cutaneous tuberculosis. Herein we
      report two interesting cases of multifocal cutaneous tuberculosis in malnourished
      children.

PMID- 22957929
TI  - Obesity and overweight in intellectual and non-intellectually disabled children.
AB  - BACKGROUND: Few studies have compared overweight and obesity in intellectually
      disabled (ID) and non-intellectually disabled (N-ID) children. This research
      compared the prevalence of overweight and obesity between a sample of 218 ID and
      229 N-ID school pupils in Northern Ireland (NI). Comparison of the physical
      activity and dietary behaviour of the two groups of school pupils were also
      undertaken. METHODS: Each pupil completed (assisted if required) a food intake
      and physical activity questionnaire. Following this body mass index (BMI) and
      waist circumference were measured and recorded. RESULTS: Significantly more ID
      pupils (72, 33%) were overweight/obese compared with 55 (24%) of the N-ID pupils
      in accordance with their BMI. ID pupils also had significantly higher waist
      circumferences. Over a quarter of foods consumed by the pupils were fatty and
      sugary foods and close to 30% of these foods were eaten by the ID children.
      Pupils spent most of their time engaging in low levels of activity such as
      reading, watching TV, on games consoles and listening to music. Pupils with an ID
      spent fewer hours on moderate and high levels of activities compared with those
      children with N-ID. CONCLUSIONS: Results of this study found higher levels of
      overweight and obesity in this sample than in international published research.
      Additionally significantly higher numbers of ID pupils were overweight and obese
      indicating the need for future research and public health to focus on this issue.

PMID- 22957928
TI  - The Interactions between L-tyrosine based nanoparticles decorated with folic acid
      and cervical cancer cells under physiological flow.
AB  - Many anticancer drugs have been established clinically, but their efficacy can be
      compromised by nonspecific toxicity and an inability to reach the desired
      cancerous intracellular spaces. In order to address these issues, researchers
      have explored the use of folic acid as a targeted moiety to increase specificity
      of chemotherapeutic drugs. To expand upon such research, we have conjugated folic
      acid to functionalized poly(ethylene glycol) and subsequently decorated the
      surface of l-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles
      possess the appropriate size (100-500 nm) for internalization as shown by
      scanning electron microscopy and dynamic light scattering. Under simulated
      physiological flow, LTP nanoparticles decorated with folic acid (targeted
      nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell
      line, compared to control nanoparticles and to human dermal fibroblasts. The
      attachment of these targeted nanoparticles progresses at a linear rate, and the
      strength of this nanoparticle attachment is shown to withstand shear stresses of
      3.0 dyn/cm(2). These interactions of the targeted nanoparticles to HeLa are
      likely a result of a receptor-ligand binding, as a competition study with free
      folic acid inhibits the nanoparticle attachment. Finally, the targeted
      nanoparticles encapsulated with a silver based drug show increased efficacy in
      comparison to nondecorated (plain) nanoparticles and drug alone against HeLa
      cells. Thus, targeted nanoparticles are a promising delivery platform for
      developing anticancer therapies that overexpress the folate receptors (FRs).

PMID- 22957930
TI  - Implantation of the heartmate II in a patient of 34 years after a Mustard
      procedure.
AB  - A growing number of patients have undergone the Mustard procedure for
      transposition of the great arteries, after which the morphologic right ventricle
      serves as the systemic ventricle. If this ventricle fails, ventricular assist
      device support may be necessary, but implanting the inflow cannula can be
      challenging in these patients because of the moderator band and trabeculation of
      the morphologic right ventricle. We describe successful assist device
      implantation in a 34-year-old patient who had undergone the Mustard procedure in
      infancy.

PMID- 22957931
TI  - Escherichia coli cold-shock gene profiles in response to over-expression/deletion
      of CsdA, RNase R and PNPase  and relevance to low-temperature RNA metabolism.
AB  - Cold-shock response is elicited by the transfer of exponentially growing cells
      from their optimum temperature to a significantly lower growth temperature and is
      characterized by the induction of several cold-shock proteins. These proteins,
      which presumably possess a variety of different activities, are critical for
      survival and continued growth at low temperature. One of the main consequences of
      cold shock is stabilization of the secondary structures in nucleic acids leading
      to hindrance of RNA degradation. Cold-shock proteins, such as RNA helicase CsdA,
      and 3'-5' processing exoribonucleases, such as PNPase and RNase R, are presumably
      involved in facilitating the RNA metabolism at low temperature. As a step toward
      elucidating the individual contributions of these proteins to low-temperature RNA
      metabolism, the global transcript profiles of cells lacking CsdA, RNase R and
      PNPase proteins as well as cells individually over-expressing these proteins as
      compared to the wild-type cells were analyzed at 15  degrees C. The analysis
      showed distinct sets of genes, which are possible targets of each of these
      proteins. This analysis will help further our understanding of the low
      temperature RNA metabolism.

PMID- 22957932
TI  - Dry eye syndrome in aromatase inhibitor users.
AB  - BACKGROUND: Aromatase inhibitors are frequently used as an adjuvant therapy in
      the treatment of breast cancer. We observed that several patients taking
      aromatase inhibitors presented with severe dry eye symptoms, and we investigated
      whether there is a relationship between aromatase inhibitors and dry eyes in
      these patients. DESIGN: Retrospective chart review. PARTICIPANTS: Forty-one
      women. METHODS: A computerized search of health records was performed to identify
      patients using anastrazole, letrozole and exemestane seen by the Cornea Service
      from August 2008 to March 2011. The results were compared with age-matched
      controls. MAIN OUTCOME MEASURES: Ocular surface changes among aromatase
      inhibitors users. RESULTS: Of the 41 women, 39 were Caucasians. Thirty-nine
      patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one
      had an unknown primary cancer. Mean age was 68 +/- 11.3 years (range 47-95). Most
      common presenting symptoms were blurred vision in 28 (68%) patients,
      irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%)
      patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients.
      Mean Schirmer's test measurement was 11 +/- 5.8 mm (range 0.5-20 mm). Blepharitis
      was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes
      (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis
      in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome
      was found in only 9.5% of patients. CONCLUSIONS: Because the prevalence of ocular
      surface disease signs and symptoms appears to be higher in study group than
      control patients, aromatase inhibitors might be a contributing factor to the dry
      eye symptoms.

PMID- 22957934
TI  - One-dimensional TiO2@Ag nanoarchitectures with interface-mediated implementation
      of resistance-switching behavior in polymer nanocomposites.
AB  - A nanocomposite capable of showing a resistance-switching behavior is prepared
      using novel resistance-switchable fillers embedded in a polymer matrix. The
      filler in this study employs a conformal passivation layer of highly crystalline
      TiO2 on surfaces of conductive Ag nanowires to effectively gate electron flows
      delivered through the conductive core, resulting in an excellent resistance
      switching performance. A nanocomposite prepared by controlled mixing of the
      resistance-switchable nanowires with a polymer matrix successfully exhibited a
      resistance-switching behavior of highly enhanced reliability and a resistance
      on/off ratio, along with flexibility due to the presence of nanowires of a tiny
      amount. The advantages of our approach include a simple and low-cost fabrication
      procedure along with sustainable performances suitable for a resistance-switching
      random-access-memory application.

PMID- 22957933
TI  - Serum metabolomics in a Helicobacter hepaticus mouse model of inflammatory bowel
      disease reveal important changes in the microbiome, serum peptides, and
      intermediary metabolism.
AB  - Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of
      the bowel. The etiology remains unknown, but IBD is immune-driven and multiple
      factors including genetic, environmental, and microbiological components play a
      role. Recombinase-activating gene-2-deficient (Rag2(-/-)) mice infected with
      Helicobacter hepaticus (H. hepaticus) have been developed as an animal model to
      imitate naturally occurring inflammatory events and associated key features of
      chronic inflammatory responses in humans. In this study, we have combined mass
      spectrometry-based metabolomics and peptidomics to analyze serum samples of Rag2(
      /-) mice infected with H. hepaticus. Metabolomics profiling revealed that H.
      hepaticus infection dramatically changed numerous metabolite pathways, including
      tryptophan metabolism, glycerophospholipids, methionine-homocysteine cycle,
      citrate cycle, fatty acid metabolism and purine metabolism, with the majority of
      metabolites being down-regulated. In particular, there were notable effects of
      gut microflora on the blood metabolites in infected animals. In addition, the
      peptidomics approach identified a number of peptides, originating from proteins,
      including fibrinogen, complement C4, and alpha-2-macroglobulin, with diverse
      biological functions with potentially important implications for the progress of
      IBD. In summary, the strategy of integrating a relevant animal model and
      sensitive mass spectrometry-based profiling may offer a new perspective to
      explore biomarkers and provide mechanistic insights into IBD.

PMID- 22957935
TI  - Buccal bone remodeling after tooth extraction using the flapless approach with
      and without synthetic bone grafting. A histomorphometric study in dogs.
AB  - OBJECTIVE: The aim of this study was to evaluate buccal bone remodeling of fresh
      sockets following tooth extraction using the flapless approach, with or without
      synthetic graft materials. MATERIAL AND METHODS: Eight dogs had the mandibular
      bicuspids extracted without flaps, and two alveoli on each side (total of 4) were
      selected. The following groups were devised: one socket on each side received a
      grafting material (test group), and the other remained only with a blood clot
      (control group). Ground sections were prepared from 12-week healing biopsies, and
      histomorphometry was performed. RESULTS: The buccal crest level (BCL) relative to
      the new bone (i), in the test group, showed numerically better data when compared
      with the control group, but without statistical relevance. The BCL relative to
      the old bone (ii) was very similar for the groups without statistical relevance.
      The alveolar ridge width (ARW) showed similar results without statistically
      significant difference between the groups. The total bone area (TBA) showed
      statistically significant differences between the test (38.60%) and control
      (47.18%) groups. The new bone area (NBA) presents a numerical difference between
      the test (15.62%) and control (22.24%), but without statistically significant
      differences. The old bone and the bone marrow were similar for both groups.
      CONCLUSION: It was observed that there was no loss of the buccal bone crest in
      relation to the lingual bone crest, especially in the test group.

PMID- 22957936
TI  - The influence of drug use in university hospitals on the pharmaceutical
      consumption in their surrounding communities.
AB  - AIM: To investigate the influence of hospital drug choices on pharmaceutical
      consumption for nine competitive classes in the surrounding community. METHODS:
      Ecological study. Data from the national survey on drugs in hospitals were used
      to extract quantities purchased by 25 French university hospitals for three
      'hospital classes' (EPOs, LMWHs and setrons) and six 'ambulatory classes' (PPIs,
      ACEIs and ARBs, statins, alpha-adrenoreceptor antagonists (AAAs) and selective
      serotonin re-uptake inhibitors SSRIs). Re-imbursed quantities for patients living
      in the hospital's catchment area were extracted from the national health
      insurance database. The relationship between the use of a brand in hospitals and
      their catchment areas was assessed using multivariate linear regressions with
      instrumental variables. RESULTS: An increase of 1 day of treatment with one brand
      in the hospital was associated with a significant increase of 2.8 days of
      treatment with the same brand in the catchment area. However, results strongly
      varied according to classes. An increase of 1 day of treatment in the hospital
      was significantly associated with an increase of 0.21 day for 'hospital classes'
      and 21.8 days for 'ambulatory classes' in the catchment area. Strong variations
      were seen across 'ambulatory classes'. The effect was maximal for cardiovascular
      classes and not significant for AAAs and SSRIs. The size of the effect also
      varied with hospital characteristics: small and proximity university hospitals
      exerted the greatest influence. CONCLUSIONS: Hospital consumption influences the
      use of drugs in the community. A significant effect was found, especially for
      competitive classes used on a long-term basis. The economic consequences of these
      findings need to be addressed.

PMID- 22957937
TI  - In vivo methods for the analysis of the penetration of topically applied
      substances in and through the skin barrier.
AB  - The efficacy of a drug is characterized by its action mechanism and its ability
      to pass the skin barrier. In this article, different methods are discussed, which
      permit this penetration process to be analysed non-invasively. Providing
      qualitative and quantitative information, tape stripping is one of the oldest
      procedures for penetration studies. Although single cell layers of corneocytes
      are removed from the skin surface, this procedure is considered as non-invasive
      and is applicable exclusively to the stratum corneum. Recently, optical and
      spectroscopic methods have been used to investigate the penetration process.
      Fluorescence-labelled drugs can be easily detected in the skin by laser scanning
      microscopy. This method has the disadvantage that the dye labelling changes the
      molecular structures of the drug and consequently might influence the penetration
      properties. The penetration process of non-fluorescent substances can be analysed
      by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton
      microscopic measurements. Using these methods, the concentration of the topically
      applied formulations in different depths of the stratum corneum can be detected
      by moving the laser focus from the skin surface deeper into the stratum corneum.
      The advantages and disadvantages of these methods will be discussed in this
      article.

PMID- 22957939
TI  - The fabric of life. Abstracts of the (Australian College of Mental Health
      Nursing) ACMHN's 38th International Mental Health Nursing Conference. October 3
      5, 2012. Darwin, Australia.

PMID- 22957938
TI  - New secreted toxins and immunity proteins encoded within the Type VI secretion
      system gene cluster of Serratia marcescens.
AB  - Protein secretion systems are critical to bacterial virulence and interactions
      with other organisms. The Type VI secretion system (T6SS) is found in many
      bacterial species and is used to target either eukaryotic cells or competitor
      bacteria. However, T6SS-secreted proteins have proven surprisingly elusive. Here,
      we identified two secreted substrates of the antibacterial T6SS from the
      opportunistic human pathogen, Serratia marcescens. Ssp1 and Ssp2, both encoded
      within the T6SS gene cluster, were confirmed as antibacterial toxins delivered by
      the T6SS. Four related proteins encoded around the Ssp proteins ('Rap' proteins)
      included two specifically conferring self-resistance ('immunity') against T6SS
      dependent Ssp1 or Ssp2 toxicity. Biochemical characterization revealed specific,
      tight binding between cognate Ssp-Rap pairs, forming complexes of 2:2
      stoichiometry. The atomic structures of two Rap proteins were solved, revealing a
      novel helical fold, dependent on a structural disulphide bond, a structural
      feature consistent with their functional localization. Homologues of the Serratia
      Ssp and Rap proteins are found encoded together within other T6SS gene clusters,
      thus they represent founder members of new families of T6SS-secreted and cognate
      immunity proteins. We suggest that Ssp proteins are the original substrates of
      the S. marcescens T6SS, before horizontal acquisition of other T6SS-secreted
      toxins. Molecular insight has been provided into how pathogens utilize
      antibacterial T6SSs to overcome competitors and succeed in polymicrobial niches.

PMID- 22957940
TI  - Astraodoric acids A-D: new lanostane triterpenes from edible mushroom Astraeus
      odoratus and their anti-Mycobacterium tuberculosis H37Ra and cytotoxic activity.
AB  - Tuberculosis (TB) is one of the chronic infectious diseases caused by
      Mycobacterium tuberculosis that causes about 2-3 million deaths per year.
      Isoniazid and rifampicin are examples of first line drugs used for TB treatment;
      however, they are potentially hepatotoxic. More effective and safer drugs are
      urgently needed, especially from natural products. Basidiomycete mushrooms are
      known as important sources of pharmaceutically active metabolites including an
      anti-TB agent. In this work, the chemical constituents of the edible mushroom
      Astraeus odoratus were isolated and investigated for antibacterial activity
      against M. tuberculosis H(37)Ra. The cytotoxic activity against cancerous cell
      lines was also evaluated. Four new lanostane triterpenes, astraodoric acids A-D,
      and new 5-hydroxyhypaphorine have been isolated together with four known
      compounds. The structures were elucidated by NMR spectroscopic methods, HR-ESI-MS
      results, and X-ray crystallographic analysis. Astraodoric acids A and B exhibited
      moderate antibacterial (MICs of 50 and 25 MUg/mL) and cytotoxic activities
      (IC(50) values of 34.69 and 18.57 MUg/mL against KB and 19.99 and 48.35 MUg/mL
      against NCI-H187), respectively. The results of this study show that A. odoratus
      could be a significant natural source for safer antitubercular and anticancer
      agents.

PMID- 22957941
TI  - LSD1 inhibition: a therapeutic strategy in cancer?
AB  - INTRODUCTION: The role of epigenetic dysfunction in cancer is increasingly
      appreciated. This has raised the question as to whether enzymes that regulate the
      structure and function of chromatin might represent novel therapeutic targets.
      The histone demethylase LSD1 is one such candidate and novel, potent inhibitors
      are under development. AREAS COVERED: The literature on LSD1 (also known as
      KDM1A, AOF2, BHC110 or KIAA0601) was identified in Pubmed and is herein
      discussed. Areas covered include the structure and enzymatic activity of LSD1,
      its role in chromatin regulatory complexes, its functional roles in normal and
      malignant tissue, pharmacological inhibitors of its activity and their putative
      therapeutic roles. EXPERT OPINION: Pre-clinical data supporting a therapeutic
      role for LSD1 inhibitors are most encouraging in acute myeloid leukaemia,
      although optimal dosing strategies and beneficial combinations with other agents
      remain unclear. Studies making use of potent, selective LSD1 inhibitors active in
      the nanomolar range are required to establish therapeutic indications in other
      subtypes of haematological malignancy, and in solid tumours.

PMID- 22957942
TI  - Relocating from out-of-area treatments: service users' perspective.
AB  - Asylum closures over recent decades resulted in mental health services being
      increasingly sited in the community. However, under provision of highly supported
      accommodation led to service users being placed away from their local area in
      'out-of-area treatments' (OATs). OATs have raised major concerns in relation to
      enabling service users' recovery, owing to limitations in promoting autonomy,
      social dislocation and costs. In 2004, an OATs project was set up in a London
      Borough to address these concerns. In the first 4 years, the project succeeded in
      relocating 22 service users to less restrictive environments locally. This study
      aims to explore the outcome of relocation from service users' perspective. A
      qualitative methodology was utilized. Semi-structured interviews were carried out
      with seven service users who relocated. All seven service users shared a strong
      aspiration for independent living but there was associated loneliness. Five
      welcomed increased contact with family and friends, but lacked social confidence,
      inhibiting social inclusion. Service users with long-term and consistent care
      managers were more able to address fears. Five out of seven service users
      concluded that relocation increased their autonomy thus enhanced their quality of
      life.

PMID- 22957943
TI  - Oxidation processes in Sicilian olive oils investigated by a combination of
      optical and EPR spectroscopy.
AB  - Extra virgin olive oil (EVOO) is recognized as one of the healthiest foods for
      its high content of antioxidants, which forestall and slow down radical
      formation. Free radical-initiated oxidation is considered one of the main causes
      of rancidity in fats and oils. As a consequence, reliable protocols for the
      investigation of oil oxidation based on selective, noninvasive, and fast methods
      are highly desirable. Here we report an experimental approach based on UV-Vis
      absorbance, steady-state fluorescence, and electron paramagnetic resonance (EPR)
      spectroscopy for studying oxidation processes induced by temperature for a period
      up to 35 d on Sicilian EVOO samples. We followed the decrease in beta-carotene
      content during incubation time and observed changes in polyphenols and
      tocopherols during the oxidation processes, focusing on the time scale of those
      changes. Using EPR spectroscopy, the free radical formation in different oil
      samples is reported, providing a fingerprint for both the antioxidant content and
      temporal features of the oxidation process at its early stage. PRACTICAL
      APPLICATION: We monitor beta-carotene and chlorophyll in an auto-oxidation
      process. A protocol based on spectroscopic measurements is presented and can be
      used for the quality control process of commercial olive oil.

PMID- 22957944
TI  - Predictive factors of response to intravenous ciclosporin in severe ulcerative
      colitis: the development of a novel prediction formula.
AB  - BACKGROUND: When treating patients with severe ulcerative colitis (UC), accurate
      prediction of drug efficacy contributes to early clinical decision-making. AIM:
      To identify predictive factors and to develop a reliable prediction formula and a
      decision tree of response to intravenous ciclosporin treatment for severe UC.
      METHODS: Patients included in this study were those diagnosed with refractory
      severe UC who had undergone ciclosporin treatment between December 2004 and March
      2011 at a tertiary referral centre in Japan. Demographic and clinical parameters
      from all patients were analysed by multivariate statistics. RESULTS: Fifty-two
      patients were included in this study (36.5% men with an average age of
      ciclosporin initiation of 40.2 +/- 15.6 years). Thirty-four patients (65.4%) were
      responders to the treatment with ciclosporin and avoided colectomy, 18 patients
      (34.6%) were nonresponders and underwent colectomy. Stepwise multiple logistic
      regression analysis identified four independent predictive factors of response to
      intravenous ciclosporin: age at hospitalisation (AGE), platelet count (*10(4)
      /MUL) on the first day (PLA), Lichtiger score on the third day (LIC) and total
      protein (g/dL) on the third day minus total protein on the first day (DeltaTP).
      The calculation formula (8.5 - 0.16 * AGE + 0.21 * PLA - 0.61 * LIC + 2.3 *
      DeltaTP < 0) predicted colectomy with an accuracy of 88.5% and the decision tree
      predicted colectomy with an accuracy of 90.4%. CONCLUSION: The novel calculation
      formula and the decision tree effectively predict the clinical outcome of
      ciclosporin treatment for severe ulcerative colitis as early as on day 3 after
      starting ciclosporin treatment.

PMID- 22957945
TI  - Severe portopulmonary hypertension associated with an unusual pattern of
      abernethy malformation: three-dimensional computed tomography view.

PMID- 22957946
TI  - Multireceptor analysis in human neocortex reveals complex alterations of receptor
      ligand binding in focal epilepsies.
AB  - PURPOSE:   A disturbed balance between excitatory and inhibitory
      neurotransmission underlies epileptic activity, although reports concerning
      neurotransmitter systems involved remain controversial. METHODS:   We quantified
      densities of 15 receptors in neocortical biopsies from patients with
      pharmacoresistant focal temporal lobe epilepsy and autopsy controls, and searched
      for correlations between density alterations and clinical factors or the
      occurrence of spontaneous synaptic potentials in vitro. KEY FINDINGS:   alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-d
      aspartate (NMDA), peripheral benzodiazepine, muscarinic (M)(1) , M(2) ,
      nicotinic, alpha(1) , alpha(2h) , serotonin (5-HT)(1A) , and adenosine (A)(1)
      receptor densities were significantly altered in biopsies. The epileptic cohort
      was subdivided based on clinical (febrile seizures, hippocampal sclerosis,
      neocortical pathologies, surgery outcome) or electrophysiologic (spontaneous
      field potentials) criteria, resulting in different patterns of significantly
      altered receptor types when comparing a given epileptic group with controls. Only
      AMPA, kainate, M(2) , and 5-HT(1A) receptors were always significantly altered.
      gamma-Aminobutyric acid (GABA)(A) , GABA(B) , and 5-HT(2) receptor alterations
      were never significant. Correlation patterns between receptor alterations and
      illness duration or seizure frequency varied depending on whether the epileptic
      cohort was considered as a whole or subdivided. SIGNIFICANCE:   Neocortical
      temporal lobe epilepsy is associated with a generalized receptor imbalance
      resulting in a net potentiation of excitatory neurotransmission. Peripheral
      benzodiazepine receptor alterations highlight that astrocytes are also impaired
      by seizure activity.

PMID- 22957948
TI  - Reflections on the DSM-5 and its relevance to psychiatric nursing.

PMID- 22957947
TI  - Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen
      receptor modulator.
AB  - Structural modification performed on a 4-methyl-4-(4-hydroxyphenyl)hydantoin
      series is described which resulted in the development of a new series of 4
      (hydroxymethyl)diarylhydantoin analogues as potent, partial agonists of the human
      androgen receptor. This led to the identification of (S)-(-)-4-(4-(hydroxymethyl)
      3-methyl-2,5-dioxo-4-phenylimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile
      ((S)-(-)-18a, GLPG0492) evaluated in vivo in a classical model of orchidectomized
      rat. In this model, (-)-18a exhibited anabolic activity on muscle, strongly
      dissociated from the androgenic activity on prostate after oral dosing. (-)-18a
      has very good pharmacokinetic properties, including bioavailability in rat (F >
      50%), and is currently under evaluation in phase I clinical trials.

PMID- 22957949
TI  - DSM-5: implications for mental health nursing education.
AB  - Three broad areas related to changes in DSM-5 are addressed in this article, and
      their implications for mental health nursing (MHN) education are discussed. The
      first area is the changes in structure and in the classification and description
      of mental disorders; knowledge of these is necessary so that nurse educators can
      teach students about the new faces of pathology in DSM-5 and what these changes
      mean for their future practice. Second, nurse educators must prepare advanced
      practice nurses to deal with the realities of the issues, criticisms, and
      concerns surrounding use of the DSM, including the influence of market forces on
      diagnosis, the validity and reliability of diagnosis, and cultural bias in
      diagnosis. Finally, there are additional concerns in preparing primary care
      nurses (nurse practitioners [NPs]) for the changes to DSM-5. It is not only
      psychiatric mental health (PMH) advanced practice nurses who must be aware of DSM
      changes and issues. The majority of mental health care in the United States is
      given in primary care settings and NPs must be prepared to assess and diagnose
      psychiatric disorders. The challenge to PMH nursing education is twofold:
      upholding the clinical role of advanced practice nurses in delivering mental
      health care, and maintaining the humanism and emphasis on quality care that has
      long characterized PMH nursing practice.

PMID- 22957950
TI  - Religious and spiritual issues in DSM-5: matters of the mind and searching of the
      soul.
AB  - Religion, spirituality, and psychiatric illnesses share a complex relationship in
      the realm of diagnosis. Historically, however, these three constructs have
      existed in a very peripheral place in the diagnostic taxonomy for psychiatry in
      the United States. Given the important role that spirituality and religion play
      for many people in the experiences of coping with health and illness, it seems
      odd that such important elements are in the margins of the powerful and
      commanding nosology of the DSM. Explanations for understanding the glaring
      absence are complex and impacted by some very powerful political and sociological
      forces, including contributory elements from within the mental health
      disciplines. This article invites the reader to explore salient issues in the
      emergence of a broader recognition of religion, spirituality and psychiatric
      diagnosis in the DSM-5.

PMID- 22957951
TI  - Issues of diagnosis and care for the transgender patient: is the DSM-5 on point?
AB  - The experience of individuals who happen to be transgender is one that reflects a
      complex constellation of powerful influences both within and outside of the
      health care system in the United States. Profound stigma, prejudice,
      misunderstanding, and hate for these individuals are just a few examples of the
      formidable challenges that potently shape their lives. The combination of exposed
      vulnerabilities in the expression of their true selves, and the often hostile
      environment where this transformation occurs creates the perfect storm for the
      onset of serious psychiatric illnesses. Oddly enough, the pathology is often not
      wrought in the experience of the genuine self but more so in what happens to that
      self in the context of a violent environment. This article explores these factors
      in the context of psychiatric diagnosis in the DSM-5.

PMID- 22957952
TI  - Hoarding's place in the DSM-5: another symptom, or a newly listed disorder?
AB  - Hoarding behavior, long considered a symptom of obsessive-compulsive disorder
      (OCD) in the Diagnostic and Statistical Manual (DSM-IV-TR; American Psychiatric
      Association, 2000), has recently garnered significant attention and has only
      begun to be more carefully studied and understood. Recent research reveals that
      hoarding is frequently comorbid with anxiety, depression, and other diagnoses,
      including OCD. The DSM-5 Working Group on Anxiety, Obsessive-Compulsive Spectrum,
      Posttraumatic, and Dissociative Disorders is currently working to determine
      appropriate placement of hoarding in the DSM-5 (APA, 2010), and has tentatively
      proposed the term Hoarding Disorder to be used as a new and unique diagnosis. The
      purpose of this paper is to provide some insight into the evidence base that has
      prompted this change and to familiarize clinicians with research and best
      practices in the emerging field of diagnosing and treating hoarding behaviors.

PMID- 22957953
TI  - The plight of personality disorders in the DSM-5.
AB  - This article provides a brief history of the development of the Diagnostic and
      Statistical Manual of Mental Disorders published by the American Psychiatric
      Association, and how it relates to the proposed fifth edition to be published in
      2013. Of particular emphasis is Axis II and how this axis is likely to be
      restructured. The reconceptualization of the nosology for personality disorders
      has been controversial since the publication of the DSM-III-R (Wilson, 1993). In
      both the clinical and academic communities, ongoing debate about diagnostic
      classification of personality disorders has been common. One recurrent theme
      among the deliberations on diagnosis and personality disorder focuses on the
      question of whether distinct (categorical) diagnoses exist or whether diagnoses
      are dimensionally related to each other in some empirically determined way. The
      proposed changes for Axis II in the DSM-5 are likely to bridge the gap between
      these two arguments by revamping the overall criteria and discarding the three
      currently used diagnostic clusters. The resulting nosology proposes six
      personality disorders with common factors in Criteria A and Criteria B. However,
      a major concern and a continuing problem not likely to be resolved in this
      edition is the symptom resemblance of borderline personality disorder and bipolar
      disorder. This article suggests some ways the revised DSM might affect mental
      health nursing practice.

PMID- 22957954
TI  - DSM-5 changes on the horizon: substance use disorders.
AB  - The first edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM) was published in 1952. This publication was the first formal attempt to
      provide a nosology to guide the diagnosis of mental disorders, including
      substance use disorders (SUD). There have been four iterations of the nosology
      since 1952, and the sequential publication of each new edition has provided the
      foundation for a more enlightened perspective on diagnosing the range of
      psychiatric conditions. This article reviews the literature specific to the past
      revisions of the DSM up to and including the proposed changes on substance
      abuse/use for the DSM-5, the significance of substance use pathology, associated
      behaviors, as well as the social and political influences that impact substance
      use. Nosological changes will be reviewed as they relate to shifts in the
      conceptualization of substance-related diagnosis.

PMID- 22957955
TI  - A nursing diagnostic perspective on proposed criteria for substance use
      disorders: what the DSM-5 is leaving out.

PMID- 22957956
TI  - Women and the DSM-5: a clinician's response to the question of invisibility.
AB  - Diagnosis of psychiatric conditions is a topic that is currently receiving
      significant attention in light of the release of the 5th edition of the
      Diagnostic and Statistical Manual of Mental Disorders in 2013. The process of the
      revisions is complex and involves political, social, and economic influences, all
      of which are amplified in an evolving corporate health care system in the United
      States. Of particular concern in the development of the revised nosology is the
      representation of gender-specific diagnoses and course specifiers to reflect the
      distinct manifestations of the psychiatric symptoms of women. Based on a growing
      body of psychobiological evidence related to gender differences in symptom
      manifestation, gender specific diagnoses remain palpably absent from the
      taxonomy. This article explores the issue of invisibility of women-specific
      diagnosis from the perspective of a women's health advanced practice nurse.

PMID- 22957957
TI  - Neurocognitive diagnostic challenges and the DSM-5: perspectives from the front
      lines of clinical practice.
AB  - The proposed changes to the DSM-IV-TR are an attempt to advance a common language
      to be used by clinicians and researchers in psychiatry in the United States. Any
      improvement brought about by these changes may be jeopardized unless the ICD-10,
      which is used by non-psychiatric clinicians and researchers worldwide, and the
      DSM resolve the differences in the definitions and diagnostic criteria of most
      disorders. Unless there is congruence between the two manuals, debate is
      therefore likely to continue in the literature as to which provider is best
      suited to direct the care for the person with dementia: primary care providers,
      psychiatric providers, or neurologists. The changes to the DSM-IV-TR have the
      potential to promote preventive measures and early diagnosis, provided that the
      stigma associated with mental illnesses can be mitigated. A common language among
      psychiatric and primary care APRNs, other clinicians, and researchers will
      enhance effective communication and improve dementia care.

PMID- 22957959
TI  - Temperament and personality: from Galen to DSM 5.

PMID- 22957960
TI  - The effects of stochastic and episodic movement of the optimum on the evolution
      of the G-matrix and the response of the trait mean to selection.
AB  - Theoretical and empirical results demonstrate that the G-matrix, which summarizes
      additive genetic variances and covariances of quantitative traits, changes over
      time. Such evolution and fluctuation of the G-matrix could potentially have wide
      ranging effects on phenotypic evolution. Nevertheless, no studies have yet
      addressed G-matrix stability and evolution when movement of an intermediate
      optimum includes large, episodic jumps or stochasticity. Here, we investigate
      such scenarios by using simulation-based models of G-matrix evolution. These
      analyses yield four important insights regarding the evolution and stability of
      the G-matrix. (i) Regardless of the model of peak movement, a moving optimum
      causes the G-matrix to orient towards the direction of net peak movement, so that
      genetic variance is enhanced in that direction (the variance enhancement effect).
      (ii) Peak movement skews the distribution of breeding values in the direction of
      movement, which impedes the response to selection. (iii) The stability of the G
      matrix is affected by the overall magnitude and direction of peak movement, but
      modes and rates of peak movement have surprisingly small effects (the invariance
      principle). (iv) Both episodic and stochastic peak movement increase the
      probability that a population will fall below its carrying capacity and go
      extinct. We also present novel equations for the response of the trait mean to
      multivariate selection, which take into account the higher moments of the
      distribution of breeding values.

PMID- 22957961
TI  - Glycan profiling of endometrial cancers using lectin microarray.
AB  - Cell surface glycans change during the process of malignant transformation. To
      characterize and distinguish endometrial cancer and endometrium, we performed
      glycan profiling using an emerging modern technology, lectin microarray analysis.
      The three cell lines, two from endometrial cancers [well-differentiated type (G1)
      and poorly differentiated type (G3)] and one from normal endometrium, were
      successfully categorized into three independent groups by 45 lectins.
      Furthermore, in cancer cells, a clear difference between G1 and G3 type was
      observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I
      (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA),
      Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin
      (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using
      G3 type tissues demonstrated that stage I and stage III or IV were distinguished
      depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA),
      BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer
      cells showed that only anticancer drug-sensitive cell lines had almost no
      activities to specific three lectins. Glycan profiling by the lectin microarray
      may be used to assess the characteristics of tumors and potentially to predict
      the success of chemotherapy treatment.

PMID- 22957962
TI  - Anomalous origin of left common carotid artery from the ascending aorta in a case
      of tetralogy of fallot.

PMID- 22957964
TI  - A cell-specific poly(ethylene glycol) derivative with a wheat-like structure for
      efficient gene delivery.
AB  - A novel anionic PEG derivative with a wheat-like structure, PEG-poly(AGE-Suc),
      was synthesized. The spikelet part of this polymer consisting of 9.3 pairs of
      carboxylic acid side chains was conjugated at one end of the PEG chain. The
      neutral linear PEG(1580) was designed as the stalk part to improve the
      biocompatibility of the vectors. The obtained polymer PEG-poly(AGE-Suc) was
      further modified by folate (FA) at the distal end to achieve the cell-specific
      targeting. It was confirmed that the negatively charged FA-PEG-poly(AGE-Suc)
      could coat the positively charged PEI 25K/DNA complex and form a ternary complex
      by electrostatic interaction. The addition of FA-PEG-poly(AGE-Suc) could change
      the positive charge of PEI 25K/DNA complexes to negative with no influence on the
      diameter. The ternary complex with the coat of FA-PEG-poly(AGE-Suc) could
      effectively condense DNA and protect it from degradation by DNase I. The
      nonspecific interaction between PEI 25K/DNA complexes and blood components was
      also significantly reduced by the addition of anionic PEG. The ternary complex
      PEI 25K/DNA/FA-PEG-poly(AGE-Suc) exhibited a 12-fold higher transfection
      efficiency on 293T cells compared to PEI 25K/DNA in the serum-containing medium.
      The competitive folate inhibition assay demonstrated that the higher transfection
      efficiency of PEI 25K/DNA/FA-PEG-poly(AGE-Suc) was attributed to the folate
      molecule conjugated to the distal end of FA-PEG-poly(AGE-Suc). The ternary
      complex PEI 25k/DNA/FA-PEG-poly(AGE-Suc) with low side effects and high
      transfection efficiency may be a novel effective gene delivery system.

PMID- 22957963
TI  - Interactions between exercise and nutrition to prevent muscle waste during
      ageing.
AB  - The underlying cause of sarcopenia and dynapenia (age-related strength loss) are
      not fully elucidated, but may be the result, or combination, of alterations in
      lifestyle or inflammatory and endocrine profiles. What is clear is that
      functional ability is limited and mortality risk is elevated. Mechanistically,
      muscle atrophy is the result of the prolonged periods of net negative muscle
      protein balance, brought about by the imbalance between muscle protein synthesis
      (MPS) and muscle protein breakdown (MPB). Contractile loading of skeletal muscle,
      through resistive-type exercise and amino acid ingestion both act as a strong
      stimulus for MPS and, when combined, can induce a net positive protein balance
      and muscle hypertrophy. Given that MPS in older muscles displays a blunted
      response to anabolic stimuli compared with the young, the combined effect and
      manipulation of contractile and nutrient interventions to optimize muscle
      anabolism could be extremely important for counteracting sarcopenia.
      Specifically, the dose, absorption kinetics, leucine content, but less-so the
      timing of ingestion, are important determinants of the mRNA translational
      signalling response regulating MPS. In addition, resistance exercise-induced
      rates of MPS and hypertrophy appear to be dependent on exercise volume (to
      achieve maximal muscle fibre recruitment), as opposed to the absolute load that
      is lifted. A number of recent studies in young adults lend weight to this notion
      by showing that contraction can be manipulated; allowing low load weight lifting
      to effectively stimulate rates of MPS to a level comparable with traditional high
      loads, a finding with important implications for older adults interested in
      undertaking resistance exercise.

PMID- 22957965
TI  - Immune-mediated myasthenia gravis in a methimazole-treated cat.
AB  - A 12-year-old female neutered ragdoll crossbred cat was presented for
      investigation of generalised weakness and regurgitation. The cat was being
      treated with transdermal methimazole for hyper-thyroidism, which had been
      diagnosed 10 weeks previously. An acetylcholine receptor antibody titre was
      consistent with acquired myasthenia gravis. Withdrawal of methimazole and
      treatment with pyridostigmine was followed by resolution of clinical signs and
      reduction of the acetylcholine -receptor antibody titre. Medical control of
      hyperthyroidism was subsequently achieved with carbimazole, administered in
      conjunction with pyridostigmine, and no recurrence of clinical signs was
      observed. Myasthenia gravis is an uncommon but clinically significant adverse
      effect of methimazole therapy in cats, and may be caused by immunomodulatory
      properties of this drug. An adverse drug reaction should be considered in cats
      receiving methimazole that develop myasthenia gravis, and potentially also other
      immune-mediated disorders. 

PMID- 22957966
TI  - Modeling psychological well-being and family relationships among retired older
      people in Taiwan.
AB  - Well-being is an important indicator of an individual's quality of life,
      especially for retired people. In the present study, we investigated the
      psychological well-being (PWB) of retired Taipei (Taiwan) older people and its
      associations with sex, family relationships, and health status. A structured
      questionnaire was used to measure demographics, family relationships, and
      perceived health status, as well as Ryff's PWB Scales. Data were analyzed from
      268 retired olderpeople recruited from social service centres and public parks
      from September to November 2010. The Multiple Indicators Multiple Causes model
      demonstrated a very good fit of Ryff's PWB Scales and their relations to sex,
      family relationships, and perceived health status. The link with PWB was stronger
      for family relationships than for perceived health. The Mandarin translation of
      Ryff's PWB Scales was found to be suitable and easy to administer to Taiwanese
      olderpeople. The findings suggest that nurses should note that improving family
      relations will facilitate the PWB of retired olderpeople, which results in better
      outcomes of care.

PMID- 22957967
TI  - Cutaneous Erysipelothrix rhusiopathiae (erysipeloid) infection in an
      immunocompromised child.
AB  - Erysipeloid, a cutaneous infection with the gram-positive bacillus Erysipelothrix
      rhusiopathiae, is typically an occupational dermatosis seen in persons working
      with livestock or involved in commercial fishing (fishmongers). Other more
      generalized forms of infection with this organism also exist, including a septic
      form usually associated with endocarditis. Many infections may be self-limited.
      They have rarely been reported in children or in immunocompromised patients. This
      microbe is sensitive to many mainstream antibiotic agents. 

PMID- 22957968
TI  - Hypoglycemic effect of the water extract of Pu-erh tea.
AB  - The water extraction and composition of pu-erh tea, as well as the hypoglycemic
      effect of the water extract of pu-erh tea (WEPT) in vivo and in vitro, are
      reported to investigate its hypoglycemic effect on diabetes. High-performance
      liquid chromatography and colorimetric methods are used to analyze the tea
      catechins, caffeine, polyphenols, amino acids, and polysaccharides of the WEPT.
      The effect of the WEPT on glucose uptake by cultured HepG2 cells and the
      inhibition effect of rat intestinal sucrase, maltase, and porcine pancreatic
      amylase are determined in vitro. Then, the blood glucose and insulin levels of
      intragastrically administered WEPT on fasting and oral glucose tolerance test
      (OGTT) using type 2 diabetic db/db (BKS.Cg-m +/+ Lepr(db)/J) mice are determined
      in vivo. The results showed that the WEPT dose-dependently and significantly
      increased glucose uptake by HepG2 cells and inhibited rat intestinal sucrase,
      maltase, and porcine pancreatic amylase activity. The WEPT intragastrically given
      for 4 weeks suppressed the increase in blood insulin and glucose levels of db/db
      mice fasted overnight. In OGTT, the WEPT improved impaired glucose tolerance and
      ameliorated retarded insulin response at 60 and 120 min in db/db mice. These
      results suggest that the WEPT has beneficial effects on glucose homeostasis in
      type 2 diabetes and in amendment of insulin resistance. 

PMID- 22957969
TI  - Management and outcomes of patients with epiphora referred to a specialist
      ophthalmic plastic unit.
AB  - BACKGROUND: To describe the aetiology and management of the symptom epiphora
      presenting to a specialist ophthalmic service. DESIGN: A retrospective case
      series and patient postal questionnaire of all new referrals seen in a specialist
      unit with primary symptoms of epiphora between January 2007 and December 2008.
      The study was begun in 2010 to allow a 2-year follow-up for this cohort.
      PARTICIPANTS: Two hundred thirty-seven patients were identified, of which 192 met
      the inclusion criteria. Fifty-seven were male, 135 were female, with a mean age
      of 60.7 (range 0-95) years. METHODS: Patients were identified using a key word
      search of clinic letters and a search of primary care coding. MAIN OUTCOME
      MEASURES: Duration of symptoms, referral source, aetiology and subjective
      improvement of symptoms post treatment. RESULTS: At consultation, patients had
      experienced epiphora for a mean of 41.1 (range 0.066-360) months. A diagnosis of
      partial or complete nasolacrimal duct obstruction (31.8%), dry eye with secondary
      reflex tearing (29.2%), eyelid malposition (10.4%) and multi-factorial epiphora
      (28.7%) was made after follow-up and treatment. A postal questionnaire follow-up
      showed that 25% of patients no longer had any epiphora, with 67% reporting an
      improvement in their symptoms. Final follow-up was 30-54 months. CONCLUSIONS:
      This study highlights the protean aetiology of the symptom and sign, epiphora.
      Sparse data exist on the audited success in managing this common symptom and
      sign. This study helps introduce an example of a benchmark for evaluating the
      effectiveness of epiphora. The majority of patients were referred, usually by
      ophthalmologists for lacrimal surgery.

PMID- 22957970
TI  - Resistance to changing practice from pro re nata prescriptions to patient group
      directions in acute mental health settings.
AB  - Poor practice associated with pro re nata (PRN) prescriptions in mental health is
      known to be common and can increase the risk of serious and potentially fatal
      side effects. A contributing factor to poor practice is the lack of a clear chain
      of accountability between the decision to prescribe and administer PRN
      prescriptions. To address this problem, a patient group direction (PGD) for acute
      behavioural disturbance (lorazepam 0.5-2 mg) and staff training materials were
      developed. The intention was to replace PRN prescriptions with the PGD in two
      mental health trusts. One of the potential benefits of this would be the removal
      of the contribution of PRN to high and combined dose antipsychotic prescriptions.
      This proposal, however, was met with significant resistance in both trusts and
      did not replace PRN as a result. A series of interviews and focus groups were
      conducted with 16 RMNs working in the two trusts, to explore the reasons why the
      PGD was met with resistance. Senior nurses perceived resistance to be associated
      with anxieties over increased responsibility for decision making. Junior nurses
      reported concerns regarding the medicalization of the nursing role, the paperwork
      associated with the PGD and the training approach used. Future efforts to
      implement PGDs in mental health settings must carefully consider the methods for
      engaging effectively with participating organizations, in terms of managing
      change and completing the necessary groundwork for successful implementation.

PMID- 22957971
TI  - An unusual form of mirror syndrome: a case report.
AB  - AIM: Mirror syndrome is a triad consisting of fetal hydrops, maternal edema and
      placentomegaly. Its pathogenesis is unclear and it is frequently mistaken for
      preeclampsia, even though distinguishing features can be identified. It is
      associated with an increase in fetal mortality and maternal morbility. METHODS:
      We report an uncommon case of mirror syndrome, which appeared late in pregnancy
      (38 weeks) in a young nulliparous and characterized by sudden and massive vulvar
      edema, with placentomegaly and hydramnios but without fetal hydrops. RESULTS: Our
      report is an interesting example of an unusual form of Mirror syndrome for
      several reasons. First of all, the gestational age in which the disorder appeared
      differs remarkably from the data of literature; in our case, clinical signs and
      symptoms appeared only at 37 weeks. Another difference consists in the lack of
      hypertension that represents the second most common symptom associated and
      explains the difficulty to differentiate this syndrome from preeclampsia.
      CONCLUSIONS: Although mirror syndrome is associated with an increase in perinatal
      mortality, in the case we reported the late onset of the disorder associated with
      the medical treatment and the timely decision to perform a caesarean section
      allowed the birth of a healthy baby.

PMID- 22957972
TI  - Immunoglobulin G profile in hyperacute rejection after multivisceral
      xenotransplantation.
AB  - INTRODUCTION: Xenotransplantation is a potential solution for the high mortality
      of patients on the waiting list for multivisceral transplantation; nevertheless,
      hyperacute rejection (HAR) hampers this practice and motivates innovative
      research. In this report, we describe a model of multivisceral
      xenotransplantation in which we observed immunoglobulin G (IgG) involvement in
      HAR. METHODS: We recovered en bloc multivisceral grafts (distal esophagus,
      stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n =
      20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three
      hours after graft reperfusion, we collected samples from all graft organs for
      histological study and to assess IgG fixation by immunofluorescence.
      Histopathologic findings were graded according to previously described methods.
      RESULTS: No histopathological features of rejection were seen in the rabbit
      allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the
      liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney.
      Xenograft vessels were the central target of HAR. The main lesions included
      edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis.
      IgG deposition was intense on cell membranes, mainly in the vascular endothelium.
      CONCLUSIONS: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR
      in the liver and severe HAR in the other organs. Moderate HAR in the liver
      suggests a degree of resistance to the humoral immune response in this organ.
      Strong IgG fixation in cell membranes, including vascular endothelium, confirms
      HAR characterized by a primary humoral immune response. This model allows
      appraisal of HAR in multiple organs and investigation of the liver's relative
      resistance to this immune response.

PMID- 22957973
TI  - Survival of O157:H7 and non-O157 serogroups of Escherichia coli in bovine rumen
      fluid and bile salts.
AB  - While Shiga toxin-producing Escherichia coli (STEC) reside asymptomatically
      within ruminants, particularly cattle, these strains pose a serious health risk
      to humans. Research related to STEC has historically focused upon O157:H7.
      However, with an increase in foodborne outbreaks of non-O157 origin and recent
      changes in testing for non-O157 by the U.S. Department of Agriculture Food Safety
      and Inspection Service (USDA-FSIS), there is now a critical need to understand
      the biological activity of non-O157 serogroups. The focus of this study was to
      determine whether variations exist in the ability of different serotypes of STEC
      to survive within bovine rumen fluid medium and bile salts. The results of this
      study demonstrated through viable plate count analysis that the five serotypes
      tested (O157:H7, O111:H8, O103:K.:H8, O145:H28, and O26:H11) were capable of
      growing in rumen fluid medium. However, the concentrations of the serotypes
      O103:K.:H8 and O26:H11 after 24 h were significantly less (p < 0.05) than that
      observed for the other serotypes tested. A significant decrease (p = 0.03) in the
      survival of O103:K.:H8 in 50 mg/mL of bovine bile salts in comparison to the
      other STEC strains tested was also observed. Collectively, these data suggest
      that non-O157 serogroups of E. coli respond differently to the environment of the
      bovine gastrointestinal tract. Further research is needed to elucidate how these
      differential physiological variations correlate with alterations in colonization
      success within ruminants and how they may impact human illnesses.

PMID- 22957974
TI  - Prevalence of zoonotic anisakid nematodes in Inuit-harvested fish and mammals
      from the eastern Canadian Arctic.
AB  - Human anisakidosis is a recognized Arctic zoonosis that is directly related to
      the consumption of traditional Inuit foods, particularly raw fish. The
      epidemiology of infections with the zoonotic anisakid nematodes Anisakis simplex
      and Pseudoterranova decipiens was investigated from August 2007 to July 2009 in
      Inuit-harvested fish and marine mammals from Inuit regions of Nunavik, Nunavut,
      and Nunatsiavut, Canada. Fish were tested for anisakid larvae using the pepsin
      HCl digestion method, and the stomachs or stomach contents of beluga whales,
      walruses, and three seal species were examined for anisakids. Anisakids were
      found in seven of eight fish species, as well as in ringed seals (18.2%; 31/170),
      bearded seals (75.0%; 12/16), and beluga whales (78.9%; 15/19), but not walruses
      (0%; 0/15). In fish, the odds of being infected with A. simplex and/or P.
      decipiens was 68.6 (95% confidence interval, 11.6-627.7) times higher in marine
      fish than in anadromous fish, after adjusting for length of fish. Negative
      binomial models were created for animal species with large enough sample sizes
      and parasite prevalence estimates to assess risk factors associated with anisakid
      abundance. In seals, the only risk factor significantly associated with
      increasing anisakid abundance was increasing length (p < 0.01), while in beluga
      whales, the only significant risk factor was year of capture (p = 0.03). In fish,
      length was the variable most commonly associated with increased anisakid larval
      abundance, with longer fish having significantly higher larval abundances than
      shorter fish of the same species. The presence of A. simplex and P. decipiens in
      bearded seals, ringed seals, and beluga whales from Inuit hunting grounds
      suggests that they likely act as definitive hosts for these parasites in these
      environments. With respect to zoonotic disease risk associated with Inuit country
      foods, among the species of fish examined, Atlantic tomcod, polar cod, and
      sculpins represented the greatest risk of foodborne disease from A. simplex and
      P. decipiens.

PMID- 22957975
TI  - Out with the "junk DNA" phrase.

PMID- 22957976
TI  - Metamorphosis and gonad maturation in the horn fly Haematobia irritans.
AB  - The bloodsucking horn fly, Haematobia irritans (L.) (Diptera: Muscidae), is one
      of the most damaging pests of pasture cattle in many areas of the world. Both
      male and female imagoes spend their adult stage on the host, while immature
      stages develop in dung. Our goal was to determine if the progress of H. irritans
      gonad maturation can be correlated with eye and cuticle pigmentation events that
      occur during development of the imago within the puparium. The progression of
      germline cell divisions in immature gonads was analyzed from the beginning of the
      third larval instar (48 hours after egg hatch) until imago ecdysis. In the
      developing male larval gonad, meiosis began 72 hours after egg hatch, whereas in
      females oogonia were premeiotic at 72 hours. Meiosis was not detected in females
      until the mid-pharate adult stage, 120 hours after puparium formation. Therefore,
      gonad maturation in females appears to be delayed 144 hours with respect to that
      in males. In the stages within the puparium, the timing of germline cell division
      events was correlated with the progress of pigmentation of the eyes and cuticle
      as external markers.

PMID- 22957977
TI  - Health needs of Australian Indigenous young people entering detention.
AB  - AIM: To determine whether there are different health needs associated with
      differences between Indigenous and non-Indigenous youth in detention in Brisbane,
      Queensland, Australia. METHODS: All records of young people (aged 10 to 21 years)
      taken into detention in Brisbane Queensland over the period 1 July 2001 to 30
      June 2009 were reviewed, and data were extracted documenting the mental health
      and related behaviours of those referred to the Mental Health, Alcohol, Tobacco
      and Other Drugs Service. International Statistical Classification of Diseases and
      Related Health Problems - Tenth Revision (ICD-10) criteria were applied to a
      clinical interview. ICD-10 diagnostic outcomes and reason for referral are
      presented by Indigenous status and age. RESULTS: Young male (under 14 years of
      age) Indigenous respondents are substantially over-represented in youth in
      detention. Indigenous youth in detention are disproportionately referred and
      diagnosed with a substance use problem. Referral and diagnosis of substance use
      problems was not as commonly found for non-Indigenous youth. CONCLUSIONS: Young
      Indigenous persons are substantially over-represented in those taken into
      detention in Queensland. This study shows significant differences in relation to
      mental health and substance use assessment outcomes for Indigenous and non
      Indigenous young people in youth detention in Queensland. Further research
      focusing on service delivery for Indigenous young people should focus on their
      specific needs.

PMID- 22957978
TI  - Tissue plasminogen activator does not alter development of acquired epilepsy.
AB  - PURPOSE:   Tissue plasminogen activator (t-PA), a proven therapy for acute
      ischemic stroke, is an endogenous serine protease associated with neuronal
      activity and synaptic plasticity in the brain. Its expression is enhanced after
      seizures, and is involved in seizure propagation throughout the brain. Therefore,
      the increased use of t-PA to treat stroke may have important implications for the
      development of poststroke epilepsy. Using experimental and clinical approaches,
      we investigated the role of t-PA in the development of epilepsy. METHODS:   Mice
      deficient in t-PA (t-PA(-/-) ) or mice transgenically modified to overexpress
      neuronal t-PA (T4) underwent amygdala kindling, and seizure threshold and rates
      of kindling were compared to those in wild-type mice. For the clinical study, we
      recruited acute ischemic stroke patients who either received intravenous t-PA
      treatment on admission to hospital (n = 177; cases) or did not (n = 158;
      controls). We then assessed the incidence of early and late onset seizures and
      epilepsy in these patients. KEY FINDINGS:   T4 mice were more seizure-prone than
      wild-type mice, exhibiting lower seizure thresholds (p = 0.002), but there were
      no significant differences observed in the rate of kindling development when
      comparing either T4 mice, or t-PA(-/-) mice, to their wild-type controls.
      Furthermore, we found no significant differences between the proportion of
      poststroke patients experiencing early or late seizures, or developing epilepsy,
      between those who received t-PA and those who did not. SIGNIFICANCE:  
      Overexpression of endogenous t-PA lowers seizure threshold but does not influence
      kindling epileptogenesis. Moreover, the therapeutic administration of t-PA in
      humans does not influence the development of acquired poststroke epilepsy.

PMID- 22957979
TI  - The amniotic fluid as a source of neural stem cells in the setting of
      experimental neural tube defects.
AB  - We sought to determine whether neural stem cells (NSCs) can be isolated from the
      amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite
      for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62)
      were divided into experimental (n=42) and control (n=20) groups, depending on
      prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were
      killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both
      groups underwent epigenetic selection for NSCs, followed by exposure to neural
      differentiation media. Representative cell samples underwent multiple
      morphological and phenotypical analyses at different time points. No control
      fetus (n=267) had any structural abnormality, whereas at least one type of NTD
      developed in 52% (217/418) of the experimental fetuses (namely, isolated spina
      bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49).
      Only amniotic samples from fetuses with a NTD yielded cells with typical neural
      progenitor morphology and robust expression of both Nestin and Sox-2, primary
      markers of NSCs. These cells responded to differentiation media by displaying
      typical morphological changes, along with expression of beta-tubulin III, glial
      fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes,
      and oligodendrocytes, respectively. This was concurrent with downregulation of
      Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific
      stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic
      fluid may be a practical source of autologous NSCs applicable to novel forms of
      therapies for spina bifida.

PMID- 22957980
TI  - Trophic transfer of contaminants in a changing arctic marine food web: Cumberland
      Sound, Nunavut, Canada.
AB  - Contaminant dynamics in arctic marine food webs may be impacted by current
      climate-induced food web changes including increases in transient/subarctic
      species. We quantified food web organochlorine transfer in the Cumberland Sound
      (Nunavut, Canada) arctic marine food web in the presence of transient species
      using species-specific biomagnification factors (BMFs), trophic magnification
      factors (TMFs), and a multifactor model that included delta(15)N-derived trophic
      position and species habitat range (transient versus resident), and also
      considered delta(13)C-derived carbon source, thermoregulatory group, and season.
      Transient/subarctic species relative to residents had higher prey-to-predator
      BMFs of biomagnifying contaminants (1.4 to 62 for harp seal, Greenland shark, and
      narwhal versus 1.1 to 20 for ringed seal, arctic skate, and beluga whale,
      respectively). For contaminants that biomagnified in a transient-and-resident
      food web and a resident-only food web scenario, TMFs were higher in the former
      (2.3 to 10.1) versus the latter (1.7 to 4.0). Transient/subarctic species have
      higher tissue contaminant levels and greater BMFs likely due to higher energetic
      requirements associated with long-distance movements or consumption of more
      contaminated prey in regions outside of Cumberland Sound. These results
      demonstrate that, in addition to climate change-related long-range
      transport/deposition/revolatilization changes, increasing numbers of
      transient/subarctic animals may alter food web contaminant dynamics.

PMID- 22957981
TI  - Quality and accuracy assessment of nutrition information on the Web for cancer
      prevention.
AB  - This study aimed to assess the quality and accuracy of nutrition information
      about cancer prevention available on the Web. The keywords 'nutrition  +  diet  +
      cancer  +  prevention' were submitted to the Google search engine. Out of 400
      websites evaluated, 100 met the inclusion and exclusion criteria and were
      selected as the sample for the assessment of quality and accuracy. Overall, 54%
      of the studied websites had low quality, 48 and 57% had no author's name or
      information, respectively, 100% were not updated within 1 month during the study
      period and 86% did not have the Health on the Net seal. When the websites were
      assessed for readability using the Flesch Reading Ease test, nearly 44% of the
      websites were categorised as 'quite difficult'. With regard to accuracy, 91% of
      the websites did not precisely follow the latest WCRF/AICR 2007 recommendation.
      The quality scores correlated significantly with the accuracy scores (r  = 
      0.250, p  <  0.05). Professional websites (n  =  22) had the highest mean quality
      scores, whereas government websites (n  =  2) had the highest mean accuracy
      scores. The quality of the websites selected in this study was not satisfactory,
      and there is great concern about the accuracy of the information being
      disseminated.

PMID- 22957982
TI  - Mitral hemi-arcade: an unusual modification of a rare anomaly.
AB  - Congenital anomalies of the mitral valve are rare. A mitral arcade is defined as
      a fibrous continuity between the papillary muscles and the anterior mitral
      leaflet creating a hammock like suspension. We present images of a mitral anomaly
      that consists of a direct attachment of the anterolateral papillary muscle to the
      anterior mitral leaflet, which we have labeled as a "hemi-arcade." We discuss the
      surgical findings and review the available literature regarding a mitral
      "arcade".

PMID- 22957983
TI  - Use of HbA1c in the diagnosis of diabetes mellitus in the UK. The implementation
      of World Health Organization guidance 2011.
AB  - The WHO was very clear that an HbA(1c) of 48 mmol/mol (6.5%) and above is
      diagnostic of diabetes. They were less clear regarding results that fell below 48
      mmol/mol. The WHO recognize that individuals with HbA(1c) values below the cut
      off point may still have diabetes, but give no guidance on how to investigate
      further. It is important that these individuals, who may be at increased risk of
      developing diabetes, are monitored correctly; a recommended scheme is given in
      Fig. 2; following these recommendations will ensure at-risk people are not
      overlooked and will be monitored closely. Even although it is not recommended to
      combine HbA(1c) with glucose measurement for diagnosis, the WHO did not discount
      the value of a fasting glucose and an oral glucose tolerance test to diagnose
      diabetes in selected individuals; it is the responsibility of the investigating
      doctor to choose how best to diagnose on an individual basis. This new method of
      diagnosing diabetes will identify a different cohort as having diabetes than is
      currently being diagnosed; but the process of investigation that does not require
      a fasting sample makes investigation easier, allowing more people to be
      investigated.

PMID- 22957984
TI  - Analysis of 14,008 uroliths from dogs in the UK over a 10-year period.
AB  - OBJECTIVES: To identify breed-associated risk factors for urolithiasis in dogs
      from the UK. METHODS: Records of all canine uroliths submitted to Hills Pet
      Nutrition UK for analysis at the University of Minnesota Urolith Centre over 10
      years (1997 to 2006) were reviewed. The results, along with the request forms
      completed by the submitting veterinarian, were analysed. The most commonly
      affected breeds, age and gender of the dogs were identified for each of the most
      common types of uroliths (struvite, calcium oxalate, urate, cystine and mixed).
      Pearson's chi-squared tests were performed to assess whether certain breeds of
      dogs were over-represented relative to a reference population (from an insurance
      database). RESULTS: The records of 14,008 urolith submissions were analysed. The
      relative frequency of struvite remained stable over time, whereas calcium oxalate
      decreased over the study period. Breeds found to be significantly over
      represented for calcium oxalate uroliths included the Chihuahua, miniature poodle
      and Yorkshire terrier. Staffordshire bull terriers and English bulldogs were at
      increased risk for cystine uroliths. CLINICAL SIGNIFICANCE: Associations between
      breed, gender, age and urolith formation were similar to those reported
      elsewhere. However, temporal trends and novel breed predispositions were
      identified.

PMID- 22957985
TI  - Dyspepsia is strongly associated with major depression and generalised anxiety
      disorder - a community study.
AB  - BACKGROUND: The relationship between dyspepsia and psychiatric comorbidity such
      as anxiety and depression is poorly defined. Previous studies have been limited
      by lack of standardised diagnostic criteria. AIM: To examine the prevalence and
      comorbidity of dyspepsia as defined by Rome III (6-month duration) with DSM-IV-TR
      generalised anxiety disorder (GAD) and major depressive episodes (MDE) in the
      general population. METHODS: A random population-based telephone survey was done
      using a questionnaire on symptoms of Rome III Dyspepsia, DSM-IV-TR GAD and MDE
      and their chronological relationship. RESULTS: Of the 2011 respondents 8.0%
      currently had Rome III Dyspepsia, 3.8% reported GAD and 12.4% reported MDE
      respectively. Dyspeptic subjects had a twofold increased risk of GAD (OR = 2.03,
      95% CI: 1.06-3.89, P < 0.001) and a threefold increased risk of MDE (OR = 3.56,
      95% CI: 2.33-5.43, P < 0.001). MDE and GAD most often coincided with dyspepsia in
      onset. Dyspepsia (OR = 2.48, 95% CI: 1.65-3.72 P < 0.001), MDE (OR = 2.39, 95%
      CI: 1.64-3.46, P < 0.001) and female sex (OR = 1.65, 95% CI: 1.21-2.23, P <
      0.001) independently predicted frequent medical consultations. GAD independently
      predicted high investigation expenditure (OR = 4.65, 95% CI: 1.15-18.70, P =
      0.03). CONCLUSIONS: With stringently adopted Rome III and DSM-IV-TR criteria,
      dyspepsia was strongly associated and often coincident in onset with generalised
      anxiety disorder and major depressive episodes in the community. Excessive
      healthcare utilisation should alert clinicians to risk of psychiatric
      comorbidity.

PMID- 22957986
TI  - Presence and extent of histological tumour necrosis is an adverse prognostic
      factor in papillary type 1 but not in papillary type 2 renal cell carcinoma.
AB  - AIMS:   To date, only limited information is available on the prognostic
      significance of the presence and extent of histological tumour necrosis with
      regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification.
      Thus, the aim of this study was to evaluate the prognostic impact of these
      pathological features on the clinical outcome in papillary subtypes. METHODS AND
      RESULTS:   The influence of histological tumour necrosis on the clinical outcome
      in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the
      presence of histological tumour necrosis was an independent negative prognostic
      factor for disease-free survival (P = 0.039), and a greater extent of necrosis
      (>20%) was significantly associated with both poor disease-free and overall
      survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2,
      neither the presence nor extent of histological tumour necrosis was a
      statistically significant negative prognostic factor. CONCLUSION:   Our findings
      suggest that the presence and extent of histological tumour necrosis are
      independent prognosticators in papillary RCC subtype 1, but not in papillary
      subtype 2. Thus, previously reported conflicting data regarding the prognostic
      impact of tumour necrosis in papillary RCC might be explained, in part, by
      heterogeneous subtypes.

PMID- 22957987
TI  - Does an educational intervention improve the usefulness of the Health of the
      Nation Outcome Scales in an acute mental health setting?
AB  - The purpose of the current study was to measure the effect of an educational
      intervention on the Health of the Nation Outcome Scales (HoNOS) completion rates.
      Additionally, interrater reliability and accuracy amongst nurses completing the
      instrument was assessed. We used a pre- and post-intervention design with videoed
      vignettes providing the basis for the educational intervention. Mental health
      nurses were assessed four times: at baseline, immediately after the intervention,
      1 week later and again, 2 months after the intervention. There was a non
      statistical increase in the number of patients assessed on admission using the
      HoNOS from 12.5% to 22.6%. Interrater reliability was low and did not improve
      through the course of the study. Intraclass correlation coefficients ranged 0.41
      0.48. Accuracy was poor when discrete scoring between 0-4 was analyzed but
      improved when scores were dichotomised to reflect a clinically significant cut
      off of 2 or more. The intervention improved completion rates marginally but
      interrater reliability and accuracy were low and did not improve over the study
      period. Opportunities for improvement were identified.

PMID- 22957988
TI  - EGCG inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal
      transition via the inhibition of Smad2 and Erk1/2 signaling pathways in nonsmall
      cell lung cancer cells.
AB  - Transforming growth factor-beta (TGF-beta)-mediated epithelial mesenchymal
      transition (EMT) of human lung cancer cells may contribute to lung cancer
      metastasis. It has been reported that EGCG can inhibit tumorigenesis and cancer
      cell growth in lung cancer; however, the effect of EGCG on EMT in nonsmall cell
      lung cancer (NSCLC) cells has not been investigated. In this study, we found that
      NSCLC cells A549 and H1299 were converted to the fibroblastic phenotype in
      response to TGF-beta. Epithelial marker E-cadherin was down-regulated, and
      mesenchymal marker vimentin was up-regulated simultaneously. Our results
      illustrated that TGF-beta was able to induce EMT in NSCLC cells, and EGCG would
      reverse TGF-beta-induced morphological changes, up-regulate the expression of E
      cadherin, and down-regulate the expression of vimentin. Immunofluorescent
      staining also demonstrated that E-cadherin was up-regulated and that vimentin was
      down-regulated by EGCG pretreatment. Moreover, wound-healing and the in vitro
      invasion assay showed that EGCG could inhibit TGF-beta-induced migration and
      invasion of NSCLC cells. By using the dual-luciferase reporter assay, we
      demonstrated that EGCG inhibited TGF-beta-induced EMT at the transcriptional
      level. EGCG decreased the phosphorylation of Smad2 and Erk1/2, inhibited the
      nuclear translocation of Smad2, and repressed the expression of transcription
      factors ZEB1, Snail, Slug, and Twist, and up-regulated the expression of E
      cadherin. In summary, our results suggest that EGCG can inhibit TGF-beta-induced
      EMT via down-regulation of phosphorylated Smad2 and Erk1/2 in NSCLC cells.

PMID- 22957989
TI  - Cutaneous graft versus host disease in pediatric multivisceral transplantation.
AB  - Multivisceral transplantation (MvTx) is the concurrent transplantation of the
      stomach, pancreaticoduodenal complex, and intestine, with or without the liver.
      Its use is increasing worldwide as it has been considered as a therapy for
      patients with functional disturbance of several organs. Graft-versus-host disease
      (GvHD) has been a relevant clinical problem in MvTx ever since the procedure was
      first performed, but little has been reported about its specific cutaneous
      features. Our study included all pediatric patients with clinical and
      histopathologic evidence of cutaneous GvHD who received MvTx between October 1999
      and December 2010 in University Hospital La Paz. Seventeen children underwent
      MvTx at our center during this period of time. Five patients developed cutaneous
      GvHD (29.4%). The median onset was 45.2 days after transplantation. Acute
      cutaneous GvHD, consisting of symmetrical maculopapular exanthema with prominent
      acral erythema and accentuated lesions on the face and pinnae, was clinically
      suspected and pathologically confirmed in four patients (80%). Three children
      (60%) experienced disease progression to a formation and a positive Nikolsky
      sign. Only one girl (20%) showed lichenoid GvHD. The first therapeutic approach
      was steroids and tacrolimus adjustment; many other drugs were used in refractory
      cases. Three of the five patients (60%) died with concomitant GvHD, the immediate
      cause of death being another comorbid disease. Knowledge of the features of
      cutaneous GvHD in MvTx allows clinicians early recognition and prompt therapeutic
      intervention that may prevent progression to higher-grade disease and improve
      outcomes for these patients.

PMID- 22957990
TI  - Automated quantification of zebrafish somites based on PDE method.
AB  - With the availability of high-throughput imaging machines and a large number of
      zebrafish embryos, zebrafish are clearly among the most cost-effective vertebrate
      systems for high-throughput or high-content screens with applications in drug
      discovery and biological pathway analysis. With the tremendous volume of images
      generated from large numbers of zebrafish screens, computerized image analysis
      for accurate and efficient data interpretation becomes essential. This paper
      presents an automated algorithm for a high-throughput screening pipeline for
      quantification of zebrafish somite. First, the main body is segmented using the
      level set method; then the head is removed; after that, the body is aligned and a
      coherence-enhancing filter is carried out so as to facilitate the somite
      detection. Finally, the somites can be easily extracted. Preliminary evaluation
      results are reported to demonstrate the good performance of the algorithm.

PMID- 22957991
TI  - Choroidal thickness profiles in retinitis pigmentosa.
AB  - BACKGROUND: Little quantitative information exists regarding the effect that
      retinitis pigmentosa (RP) has on the choroid. The aim of this study was to
      determine choroidal thickness profiles in patients with RP. DESIGN: Prospective.
      PARTICIPANTS: Forty-two RP and 22 control subjects participated in the study. RP
      patients had mild to severe disease, with a visual acuity range of logMAR 0.1 to
      no light perception. METHODS: Images of the retina and choroid were obtained
      using the enhanced depth-imaging method and optical coherence tomography (OCT).
      Choroidal thickness measures were determined via manual segmentation of the OCT
      image. MAIN OUTCOME MEASURES: The thickness profiles of the normal and RP groups
      were compared. The associations between choroidal thickness, visual acuity and
      duration of RP were determined. RESULTS: The choroid was thickest in the control
      eyes at the subfoveal location (336.60 +/- 70.42 MUm), and the thickness
      gradually decreased towards the peripheral retina (temporal 8 degrees  = 295.55
      +/- 60.52 MUm; nasal 8 degrees  = 251.68 +/- 49.93 MUm). In RP, the mean
      thickness was also greater at the fovea (215.60 +/- 94.91 MUm) than the temporal
      (191.66 +/- 72.42 MUm) and nasal (149.91 +/- 57.42 MUm) retina, but all values
      were significantly lower than those of the controls (P <= 0.001). Subfoveal
      choroidal thickness was significantly correlated with visual acuity (r = -0.46, P
      < 0.001) and duration of disease (r = -0.4, P = 0.001). CONCLUSIONS: Patients
      with RP have a thinner choroid than controls. Patients with poorer visual acuity
      or longer duration of symptoms tended to have thinner choroids. Knowledge of
      choroidal thickness profile in RP is important for the field of restorative
      vision research and the development of suprachoroidal retinal prostheses.

PMID- 22957992
TI  - Analysis of the temporal change in biophysical parameters after fractional laser
      treatments using reflectance confocal microscopy.
AB  - BACKGROUND: Fractional photothermolysis is a popular treatment option for
      photorejuvenation. Previous literature studies have demonstrated the clinical
      effectiveness of fractional photothermolysis on cutaneous photoaging; however,
      the associated changes in biophysical properties of the skin following fractional
      photothermolysis have not been fully elucidated. This study was conducted to
      investigate the temporal changes in biophysical parameters after fractional laser
      treatment on Asian skin. MATERIALS AND METHODS: Eleven female subjects underwent
      a single treatment with an erbium glass fractional laser. Skin roughness,
      elasticity, transepidermal water loss (TEWL), dermal thickness were evaluated
      before and immediately after treatment and 3 days, 1 week, 2 weeks, and 4 weeks
      after treatment. The changes in the dermal papilla were analyzed using a
      reflectance confocal microscopy (RCM). RESULTS: Skin roughness showed the
      greatest improvement at the first week and net elasticity was most improved at
      the second week. TEWL and the percentage of melanized and active dermal papillae
      (DP) were mostly increased for 3 days. At 4 weeks after treatment, the number of
      total dermal papillae showed a significant increase compared with pretreatment.
      CONCLUSION: This is the first study of the characterization and quantification of
      dermal papilla reflecting the dermal repair process after fractional
      photothermolysis through an RCM.

PMID- 22957993
TI  - The effect of cognitive behavioural psycho-education on premenstrual syndrome and
      related symptoms.
AB  - Premenstrual syndrome (PMS) is a distressing group of symptoms related to
      menstrual cycle during reproductive age. Its substantial burden on daily function
      and quality of life, particularly on mental aspects, was to the impetus for this
      study with the aim of determining the effectiveness of a psycho-educational
      package on premenstrual syndrome and related symptoms. In a randomized clinical
      trial, 123 (17-19-year-old) adolescent girls with PMS were randomized to psycho
      educational intervention (including 62 subjects) and control (including 61)
      groups. The participants completed a demographic questionnaire, premenstrual
      syndrome symptom daily record scale and the Symptom Checklist-90-Revised (SCL-90
      R). A paired and two independent samples t-test and chi-squared test were used
      for analysing data using SPSS statistical package. At the end of the study there
      was statistically significant decrease in severity of total PMS in intervention
      compared with control group (P < 0.001). Also, a significant difference in
      somatization, anxiety and hostility was observed between two groups (P < 0.05).
      However, depression marginally decreased (P < 0.1) in intervention group, and
      interpersonal sensitivity was not statistically different between intervention
      and control groups. Intervention alleviated the severity of PMS and related
      somatization, anxiety and hostility, yet it could not change the severity of
      depression and interpersonal sensitivity.

PMID- 22957994
TI  - Two successful national breast cancer symposia now merged and are made even
      better: an invitation to join us at Amelia Island, Florida.

PMID- 22957995
TI  - The surgical treatment of breast cancer in the elderly: a single institution
      comparative review of 5235 patients with 1028 patients >=70 years.
AB  - As the wave of the baby boomers shifts the age demographic of patients, the
      current surgical management of breast cancer in elderly women (>=70 years of age)
      becomes relevant because deviation from standard treatment often occurs in this
      group. The purpose of this study was to determine the operative mortality when
      treated with standard surgical procedures and to investigate trends in the
      surgical management of breast cancer in the elderly. A total of 5,235 patients
      undergoing either mastectomy or breast conservation surgery (BCS) for invasive
      and ductal carcinoma in situ (DCIS) were identified in a retrospective review of
      a prospectively accrued data base between the years of 1994 and 2007 at the
      Moffitt Cancer Center. Of the 5,235 patients, 1,028 (20%) patients were >=70
      years of age. The 30-day and 90-day mortality in the elderly group (age >=70
      years) was 0.2% (95% CI 0.02-0.7%) and 0.7% (95% CI 0.3-1.4%), respectively. The
      30-day and 90-day mortality among patients <70 years was 0 and 0.05% (2 of 4,207
      patients) (95% CI 0.005-0.2), respectively. BCS rates for invasive carcinomas
      were the highest for patients between 40 and 70 years of age, whereas the
      mastectomy rates were higher among patients <40 years of age (53%). Elderly women
      were as likely as women <40 years to have BCS for invasive carcinoma (OR 1.1, 95%
      CI 0.8-1.5), but more likely to have BCS for DCIS (OR 1.9, 95% CI 1.1-3.3).
      Surgical mortality in elderly women treated for breast cancer was extremely low
      and was related to the extent of surgery performed. Breast cancer treatment
      differed by age groups.

PMID- 22957996
TI  - Genetic determinants of breast cancer risk: a review of current literature and
      issues pertaining to clinical application.
AB  - Despite major advances in breast cancer therapy, annual mortality remains
      significant with a sizeable proportion of patients eventually succumbing to
      metastatic disease. Clearly, optimizing approaches for identification and
      management of women at heightened risk for breast cancer will reduce overall
      morbidity and mortality from the disease. Over the past few decades, advances in
      molecular genetics and linkage analyses have allowed for the identification of
      specific germline mutations underlying a significant fraction of hereditary
      breast cancer. Genome-wide association studies have been developed as a powerful
      tool in identifying lower penetrance mutations, and it is believed that such
      genome-level variations may act in concert to give rise to the majority of
      inherited breast cancer risk. Controversies and uncertainties remain in clinical
      application of newly identified genomic loci that confer genetic susceptibility.
      This article reviews the well-characterized breast cancer susceptibility genes,
      highlights recent publications pertaining to the less well known and lower
      penetrance genetic polymorphisms, summarizes challenges in translating research
      findings to the clinical scenario, and offers some recommendations for clinical
      practice.

PMID- 22957997
TI  - Chyle fistula after simple mastectomy and sentinel lymph node biopsy: a rare
      occurrence.

PMID- 22957998
TI  - A rare cystic breast lump - schwannoma of the breast.

PMID- 22957999
TI  - Nipple aspirate fluid producer status among premenopausal women in Hawaii.

PMID- 22958000
TI  - Male courtship behavior of the South American fruit fly, Anastrepha fraterculus,
      from an Argentinean laboratory strain.
AB  - The South American fruit fly Anastrepha fraterculus (Wiedemann) (Diptera:
      Tephritidae) is a pest of fruit species of warm regions of the Americas,
      including Argentina. Some authors claim that this taxon includes a group of
      cryptic species. In order to evaluate possible targets of sexual selection, it is
      necessary to analyze ethological aspects of male courtship and identify
      particular steps that strongly influence mating success. A mating test designed
      to evaluate behavioral differences between insects that achieve copulation
      (successful males) and those that did not mate (unsuccessful males) could also be
      relevant for the possible implementation of control programs based on sterile
      insect technique. Reared insects need to be evaluated periodically, since genetic
      drift and artificial selection associated with rearing conditions could have a
      detrimental effect on their ability to compete for matings in nature. In this
      study, courtship behavior of A. fraterculus males from a laboratory strain was
      analyzed for the first time through video recordings. Three components for the
      activities were identified: calling, wing positions, and movements. Also, the
      time that males spent on each step of the courtship was registered, including the
      last activities before attempting copulation. Data showed that mating achievement
      occurs relatively quickly; 65% of the successful males reached copulation within
      the first ten minutes after the male and female were placed together. Behavioral
      differences were detected between successful and unsuccessful males. The former
      group tended to invest more time in activities directly related with mating
      (Spin, Arrowhead, Attempt); however, as courtship progressed, unsuccessful males
      increased the time dedicated to activities not directly associated to mating
      (Call 0, Relax,Stationary). There was not a single sequence of activities leading
      to success, but the analysis of the last activities performed before mating
      attempts indicated that the most frequent position before successful attempts was
      Arrowhead, occurring in 68% of cases, whereas in unsuccessful males this position
      was observed only 18% of the time before mounting. Although the behavior of the
      strain analyzed here should be compared with that of natural populations, one
      would not expect to observe significant differences as compatibility and
      competitiveness with wild collected flies was previously shown under field cage
      conditions. Behavioral tests such as those applied here might be important to
      assess quality of mass reared strains for sterile insect technique implementation
      programs.

PMID- 22958001
TI  - Cyclic-RGD peptides increase the adenoviral transduction of human mesenchymal
      stem cells.
AB  - Human mesenchymal stem cells (hMSCs) have been extensively explored for drug
      delivery applications due to their safety, immunomodulatory properties, and
      ability to differentiate into new tissues. The experiments presented in this
      study were designed to determine peptide-based mechanisms to increase the
      adenoviral transduction of hMSCs for the purpose of improving their capacity as
      drug delivery vehicles. Specifically, we demonstrated that cyclic- RGD peptides
      increased the internalization of adenoviruses into MSCs. MSCs treated with cyclic
      RGD peptides had a transduction efficiency of 76.6%+/-4%, which was significantly
      greater than the 23.5%+/-12.2% transduction efficiency of untreated stem cells
      (P<0.05). Blocking endocytosis with inhibitors of dynamin or actin polymerization
      decreased the cyclic-RGD-mediated increase in transduction efficiency. MSCs
      treated with cyclic-RGD and adenoviruses carrying the gene for bone morphogenetic
      protein-2 produced significantly greater concentrations of this growth factor
      compared to stem cells treated with only adenoviruses or adenoviruses cocultured
      with cyclic-RAD peptides. Furthermore, this stem cell-produced bone morphogenetic
      protein induced alkaline phosphatase expression in C2C12 cells indicating growth
      factor bioactivity. Taken together, these studies suggest that cyclic-RGD
      peptides could be used to increase the adenoviral transduction of hMSCs and
      increase their therapeutic potential.

PMID- 22958002
TI  - Photokinetic, biochemical and structural features of chimeric photoactive yellow
      protein constructs.
AB  - Of the 10 photoactive yellow protein (PYPs) that have been characterized, the two
      from Rhodobacter species are the only ones that have an additional intermediate
      spectral form in the resting state (lambdamax  = 375 nm), compared to the
      prototypical Halorhodospira halophila PYP. We have constructed three chimeric PYP
      proteins by replacing the first 21 residues from the N-terminus (Hyb1PYP), 10
      from the beta4-beta5 loop (Hyb2PYP) and both (Hyb3PYP) in Hhal PYP with those
      from Rb. capsulatus PYP. The N-terminal chimera behaves both spectrally and
      kinetically like Hhal PYP, indicating that the Rcaps N-terminus folds against the
      core of Hhal PYP. A small fraction shows dimerization and slower recovery,
      possibly due to interaction at the N-termini. The loop chimera has a small amount
      of the intermediate spectral form and a photocycle that is 20 000 times slower
      than Hhal PYP. The third chimera, with both regions exchanged, resembles Rcaps
      PYP with a significant amount of intermediate spectral form (lambdamax  = 380
      nm), but has even slower kinetics. The effects are not strictly additive in the
      double chimera, suggesting that what perturbs one site, affects the other as
      well. These chimeras suggest that the intermediate spectral form has its origins
      in overall protein stability and solvent exposure.

PMID- 22958004
TI  - Thrombocytosis and thrombocytopenia in the NICU: incidence, mechanisms and
      treatments.
AB  - OBJECTIVE: Quantitative and qualitative platelet abnormalities of neonates must
      be defined using evidence-based reference ranges, constructed according to
      gestational and postnatal age. METHODS: Platelet counts, and demographic and
      outcome data, were obtained from neonates in the Intermountain Healthcare system
      in the western USA and template bleeding times were determined from neonates in
      Italy. RESULTS: Reference ranges were constructed by excluding values from
      neonates with diagnoses associated with abnormal platelet counts (small for
      gestational age (SGA), pregnancy-induced hypertension (PIH), infection and
      necrotizing enterocolitis (NEC)). Values remaining in the database after
      excluding these diagnoses were organized into 5th to 95th percentile ranges. At
      23-25 weeks gestation, thrombocytopenia (<5th percentile) was defined by a
      platelet count <100,000/ul. Severe thrombocytopenia (platelet count <50,000/ul)
      occurred in 2.4% of neonatal intensive care unit (NICU) admissions and was
      largely due to acquired consumptive causes (bacterial and fungal sepsis, NEC and
      extracorporeal membrane oxygenation). No correlation was found between platelet
      count and subsequent central nervous system (CNS), pulmonary or gastrointestinal
      (GI) bleeding. The mortality rate did not correlate with the lowest platelet
      count but was proportionate to the number of platelet transfusions received.
      Platelet transfusions, administered according to guidelines, were given to 7% of
      NICU admissions, but a change in the guidelines from "count-based" to "mass
      based" was associated with a reduction to 4%, with no increase in CNS, pulmonary,
      GI or cutaneous haemorrhage. Bleeding times were twice as long in neonates <33
      weeks gestation as in term neonates, and shortened to term values by day of life
      ten. CONCLUSIONS: When reference ranges for platelets, appropriate to gestational
      and postnatal ages, are used, more uniformity occurs in definitions. This
      uniformity will foster consistency in diagnosis, treatment and outcomes
      reporting.

PMID- 22958005
TI  - Thromboelastography: might work in neonatology too?
AB  - AIM: To review the working principles of thromboelastography and evaluate the
      current knowledge about the possibility of its implementation in the neonatal
      intensive care unit setting. METHOD: Thorough search of the literature in the
      PubMed database (until May 31, 2012) concerning Thromboelastography (TEG) and/or
      Thromboelastometry (ROTEM) use in the newborn infant. RESULTS: Neonatal data are
      limited to a small number of healthy subjects and virtually absent in the extreme
      premature infant. Healthy newborns exhibit age dependent accelerated initiation
      and propagation of coagulation despite prolonged standard plasma coagulation test
      results, whereas clot firmness and fibrinolysis are similar to adult values.
      Several neonatal pathological conditions (e.g. sepsis; hypothermia) are linked
      with substantial changes in the thromboelastographic parameters. CONCLUSIONS: The
      current knowledge is too limited to express a definitive indication on the
      reliability of the use of viscoelastic point of care analyzer in the neonatal
      intensive care unit setting. However, their potential use not only as a
      diagnostic tool, but also to guide the transfusion therapy requires careful
      consideration.

PMID- 22958006
TI  - Haematological abnormalities in neonatal necrotizing enterocolitis.
AB  - OBJECTIVE: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and
      mortality in preterm infants born prior to 32 weeks gestation or with a birth
      weight less than 1500 grams. In this article, we review hematological
      abnormalities associated with NEC. METHODS: A literature search was performed
      using the databases PubMed, EMBASE, and Scopus, and the electronic archive of
      abstracts presented at the annual meetings of the Pediatric Academic Societies.
      RESULTS: Thrombocytopenia, disseminated intravascular coagulation, increased or
      decreased neutrophil counts, and hemolytic anemia are frequent events in NEC.
      CONCLUSIONS: NEC is associated with several hematological abnormalities, which
      may play a direct or indirect role in the pathogenesis of gut mucosal injury, and
      may also carry important prognostic information.

PMID- 22958007
TI  - Central venous catheterization and thrombosis in newborns: update on diagnosis
      and management.
AB  - Very low birth weight and other critically ill neonates require prolonged
      vascular access, which is achieved in current practice with central venous
      catheters. The initiation of adequate parenteral nutrition and prolonged
      intravenous medications represent the most important applications. Central
      vascular access in neonates is associated with a high risk for mechanical,
      infectious and thrombotic complications. The use of central lines is the most
      common cause for thrombosis in neonates and infants. The management of line
      related thrombosis is based on expert opinion guidelines and is largely dependent
      on patient symptoms and the further requirement of the catheter. This review
      article focuses on pathophysiology, diagnosis, and acute and long-term management
      of catheter thrombosis in neonates.

PMID- 22958008
TI  - Chorioamnionitis and prematurity: a critical review.
AB  - Chorioamnionitis is the inflammatory response to an acute inflammation of the
      membranes and chorion of the placenta. We provide a critical review of the
      relationship between chorioamnionitis and the risk of prematurity and adverse
      maternal-fetal outcome. Chorioamnionitis results as a major risk factor for
      preterm birth and its incidence is strictly related to gestational age. It is
      associated with a significant maternal, perinatal and long-term adverse outcomes.
      The principal neonatal complications are neonatal sepsis, pneumonia,
      bronchopulmonary dysplasia, perinatal death, cerebral palsy and intraventricular
      hemorrhage. The role in neonatal outcome is still controversial and more
      conclusive studies could clarify the relationship between chorioamnionitis and
      adverse neonatal outcome. Maternal complications include abnormal progression of
      labour, caesarean section, postpartum hemorrhage, abnormal response after use of
      oxytocin and placenta abruption. Prompt administration of antibiotics and
      steroids could improve neonatal outcomes.

PMID- 22958009
TI  - Laboratory medicine in neonatal sepsis and inflammation.
AB  - The high incidence of neonatal sepsis worldwide and the considerably high
      mortality rate of severe sepsis and septic shock call for an earlier diagnosis
      and more accurate monitoring of the disease. Conventional laboratory tests, such
      as white blood cell count (WBC) and differential count, micro-erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) have a number of
      limitations associated with their limited sensitivity in the early phase of the
      disease and their non-specific increase in the course of various severe neonatal
      clinical conditions like asphyxia, meconium aspiration and prolonged rupture of
      membranes. Next-generation biomarkers encompass new molecular tests, accurate
      measurement of the proteins and enzymes mainly involved in the innate immunity
      biochemical pathways, application of proteomics and metabolomics for risk
      stratification and prognosis, and the clinical use of matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the
      identification of various bacteria and yeasts. The availability of sophisticated
      biochemical and molecular tests and of innovative technologies can significantly
      improve baby outcomes in terms of earlier and more accurate diagnosis, tailored
      therapeutic treatment, shorter hospitalization and thus minimized complications,
      and ultimately can prevent and monitor nosocomial and healthcare-associated
      infections. As a consequence, costs can be significantly reduced over a full
      cycle of care by investing in high quality laboratory medicine.

PMID- 22958010
TI  - Use and misuse of antibiotics in the neonatal intensive care unit.
AB  - Severe infections represent the main cause of neonatal mortality accounting for
      more than one million neonatal deaths worldwide every year. Antibiotics are the
      most commonly prescribed medications in neonatal intensive care units (NICUs) and
      in industrialized countries about 1% of neonates are exposed to antibiotic
      therapy. Signs and symptoms of sepsis are nonspecific, and empiric antimicrobial
      therapy is promptly initiated after obtaining appropriate cultures in order to
      prevent deleterious consequences. However, many preterm infants who do not have
      infection receive antimicrobial agents during hospital stay and antibiotic
      treatment in the setting of negative cultures can have serious adverse effects
      like: promotion of bacterial antibiotic resistance, alteration of gut
      colonization, increase risk of Candida colonization and subsequent invasive
      candidiasis, increase risk of death, necrotizing enterocolitis and late-onset
      sepsis. Appropriate choice of antimicrobial agents and optimal duration of
      therapy in neonates with suspected or culture-proven sepsis is essential in order
      to prevent serious consequences. Moreover the establishment of an antibiotic
      stewardship programme in the NICUs is the best way of ensuring neonatal
      infections remain treatable while efforts are made for the developing of optimal
      antibiotic prescribing.

PMID- 22958011
TI  - Neonatal tuberculosis: an experience that teaches.
AB  - OBJECTIVE: This study reports on an experience following contact by a large
      number of newborn babies with a nurse infected by active tuberculosis (TB).
      METHODS: A large number of newborn babies were checked for possible contact with
      Mycobacterium tuberculosis (MTB) using interferon-gamma tests (IGTs) to determine
      specific treatment. RESULTS: One hundred and seven infants showed a positive IGT
      positive and were not affected by active TB. All were treated with anti
      tubercular drugs and were followed-up for 1 year. None of the infants developed
      active TB and all infants showed normal tuberculin skin tests and chest-x-rays,
      as well as IGT results at the end of treatment. CONCLUSIONS: Our experience
      suggests that newborns are at low risk of infection after contact with a nurse
      with active TB. IGTs can be used to assess possible contact with MTB and to
      determine a reduced number of infants to treat.

PMID- 22958012
TI  - Neonatology and the caesarean section.
AB  - The origins of the use of the Caesarean section date far back in human history.
      Traces of this procedure can be found in Greek mythology and in the history of
      Ancient Rome. Many documents about the history of religion make reference to a
      delivery from the abdomen.

PMID- 22958013
TI  - Where, in which way and to what extent can Italian fertility grow in the next 15
      years?
AB  - OBJECTIVE: The study aims at analysing the recent trends in fertility in Italy
      and at discussing its possible future trends. METHODS: We analyse the evolution
      of demographic indicators, such as the total fertility rate and the maternal age
      in Italy, in the last 30 years and we look for the most relevant determinants of
      birth postponement. We also discuss the most recent fertility forecasts for Italy
      and their implications. RESULTS: In Italy, the total fertility rate has declined
      sharply in the last 30 years, reaching a level among the lowest in the world.
      However, in the last decade a reversal in this trend has been recorded. We here
      show that, net of the effect of immigration, this reversal is mainly due to a
      recovery of postponed births after age 30. Nevertheless, this recovery is not
      sufficient to raise the total fertility rates up to the replacement level. The
      reasons for this insufficient recovery are related both to the marked delay in
      transition to adulthood and to the difficult reconciliation of work and maternity
      for Italian women, both hampering the fertility rates. CONCLUSIONS: The fertility
      decline in Italy has finally stopped in the last years even if the maternal age
      is continuously increasing. However, without ad hoc family policies the fertility
      recovery will be weak and limited to those areas of the country with a better
      welfare system and economically more developed.

PMID- 22958014
TI  - Healthcare resources and expenditure in financial crisis: scenarios and
      managerial strategies.
AB  - OBJECTIVE: What are the implications of financial crisis on healthcare
      expenditure? This paper explores different approaches applied across European
      countries focusing on the role that managerial tools may have in coping with this
      challenge. METHOD: The paper reports the results of recent studies on responses
      to financial crisis from European countries and which are the techniques they had
      applied to reallocate resources. RESULTS: Although resources scarcity, some
      governments did not reduce the healthcare expenditure because they believe in its
      focal role on the economic development and on maintaining social cohesion and
      protection of vulnerable people. Other countries decided a strong reduction of
      costs which often has affected services delivered. In both cases authors suggest
      to avoid across-the-board cuts in favor of approach involving priority setting.
      CONCLUSION: The public sector has assumed new responsibilities following the
      global crisis and the rising demand for social services. Some countries shifted
      the healthcare costs from the public purse to private households undermining the
      survival of the health system and the universal coverage. A way to avoid this
      risk is based on the ability to share discussion about where to cut and where to
      reallocate resources.

PMID- 22958015
TI  - Evaluation of echocardiography in the neonatal unit.

PMID- 22958016
TI  - Follow-up of neonates with foetal and neonatal arrhythmias.

PMID- 22958017
TI  - Strategies to improve feeding tolerance in preterm infants.
AB  - Postnatal growth restriction and failure to thrive is a major issue in preterm,
      especially extremely low-birth-weight infants. Optimization of enteral nutrition,
      without increasing the risk of necrotizing enterocolitis (NEC), has thus become a
      priority for the neonatologist, who often has to face the challenge of
      interpreting the clinical and prognostic significance of common and aspecific
      signs of feeding intolerance (FI). The neonatologist often prescribes enteral
      nutrition as if walking on a tightrope between the purposed attainment of full
      enteral feeding and the fear of NEC. Despite advances in neonatal intensive care,
      NEC still remains one of the leading causes of mortality (15-30%) and morbidity
      in very-low-birth-weight infants. However, the relationship between FI and NEC
      remains unknown. Feeding intolerance often leads to discontinuation of enteral
      feeds, delayed attainment of full enteral feeding and prolongation of
      hospitalization. Strategies aimed at preventing and/or treating episodes of
      feeding intolerance are diverse and not always supported by scientific evidence.

PMID- 22958018
TI  - Detection of cow's milk proteins and minor components in human milk using
      proteomics techniques.
AB  - Cow's milk proteins (CMPs) are the best characterized food allergens. The aim of
      this study was to investigate cow's milk allergens in human colostrum of term and
      preterm newborns' mothers, and other minor protein components by proteomics
      techniques, more sensitive than other techniques used in the past. Sixty-two term
      and 11 preterm colostrum samples were collected, subjected to a treatment able to
      increase the concentration of the most diluted proteins and simultaneously to
      reduce the concentration of the proteins present at high concentration
      (Proteominer Treatment), and subsequently subjected to the steps of proteomic
      techniques. The most relevant finding in this study was the detection of the
      intact bovine alpha-S1-casein in human colostrum, then bovine alpha-1-casein
      could be considered the cow's milk allergen that is readily secreted in human
      milk and could be a cause of sensitization to cow's milk in exclusively breastfed
      predisposed infants. Another interesting result was the detection, at very low
      concentrations, of proteins previously not described in human milk (galectin-7,
      the different isoforms of the 14-3-3 protein and the serum amyloid P-component),
      probably involved in the regulation of the normal cell growth, in the pro
      apoptotic function and in the regulation of tissue homeostasis. Further
      investigations are needed to understand if these families of proteins have
      specific biological activity in human milk.

PMID- 22958019
TI  - Update on lipid and protein intakes in the critical newborn.
AB  - The influence of critical illnesses on adverse outcomes in newborn infants seems
      to be mediated by nutritional intakes during the first week or few weeks of life.
      Changes in amounts and ratios of protein and energy, fat quality (medium chain
      triglycerides, and n-3 long-chain polyunsaturated fatty acids), maintaining
      normoglycemia during full or partial parenteral nutrition, rate of feeding
      advancements and avoidance of postnatal growth retardation represent the main
      items whose roles in critically ill preterm infants have been considered so far.
      In a condition such as extreme prematurity, feeding higher amounts of amino acids
      since the first day of life has been shown so far to be safe and effective in
      terms of metabolic balance, body growth and neurodevelopment outcome. In other
      clinical conditions and as far as other nutrients are concerned, available data
      are still limited and do not allow for firm conclusions in most cases.

PMID- 22958020
TI  - ELBW infants: to intubate or not to intubate in the delivery room?
AB  - Few years ago, elective tracheal intubation in the delivery room was considered
      as the routine approach in managing respiratory failure in extremely-low-birth
      weight infants (ELBW), at least in terms of surfactant administration. Over
      recent years, the indications and principles of neonatal resuscitation of ELBW
      infants have been partially reviewed: many randomized clinical trials (RCT) have
      demonstrated that these infants do not die quickly without intubation in the
      delivery room, and many infants only need a little help in completing foetal
      neonatal transition through the use of lung recruitment manoeuvres in the
      delivery room (e.g. sustained lung inflation, CPAP) and then only non-invasive
      ventilation support. Tracheal intubation and mechanical ventilation can be
      reserved solely for depressed or ELBW, although further RCTs are needed to
      provide additional information and to provide a conclusive response to the
      eternal debate as to whether intubation at birth can influence outcome for ELBW
      infants.

PMID- 22958021
TI  - Italian survey of neonatal respiratory support strategies.
AB  - Although the management of respiratory distress syndrome (RDS) in preterm infants
      has been characterized by significant progress in recent years, it is difficult
      to translate the research results into clinical practice. Previous surveys have
      demonstrated that in some areas, the current management of RDS does not reflect
      evidence from randomized trials. Therefore, the Pulmonology Study Group of the
      Italian Society of Neonatology decided to perform a similar survey in Italy with
      the aim of identifying possible aspects of respiratory management of preterm
      infants with RDS that merit improvement, and of suggesting focused interventions
      for their resolution.

PMID- 22958022
TI  - High-flow nasal cannula: transient fashion or new method of non-invasive
      ventilatory assistance?
AB  - Respiratory failure in the premature infants remains a difficult challenge. An
      alternative to the use of nasal continuous positive airway pressure (NCPAP) as a
      non-invasive modality to support respiratory distress in premature infants has
      been the recent introduction of high flow nasal cannula (HFNC) devices in many
      neonatal units. There has been increased use of HFNC presumably because of
      anecdotal reports and experience that it is easy to use, and well tolerated by
      the infants, while experiencing decreased nasal septumerosion. The paucity of
      evidence regarding its efficacy and safety, would support a caution approach to
      the use of HFNC. Particular concern has focused on the imprecise regulation and
      generation of pressure that may occur at higher flows especially in the smallest
      of infants.

PMID- 22958023
TI  - How to reduce invasiveness in non-invasive ventilation.
AB  - Non invasive ventilation plays a key role in neonatal intensive care unit (NICU)
      activity and several instruments have recently been developed that are designed
      to maintain positive pressure in order to improve functional residual capacity of
      the lung. However, devices used to provide non-invasive respiratory assistance
      are frequently a cause of discomfort when applied to a fragile neonate. Indeed,
      they are applied for lengthy periods in low birth weight (VLBW) infants. In
      addition to these side effects we have to consider several other stressful
      events. In our opinion, reducing invasiveness in the NICU is a process where the
      main steps are recognizing a need for the organization of diagnostic and
      therapeutic procedures with respect for the rhythm of the newborn, recognizing
      the fragility of preterm newborns and their brain plasticity, improving
      environmental standards in both structural terms and staff behaviour, and
      promoting the active role of parents in supporting the development of the
      newborn.

PMID- 22958024
TI  - Growth and neurological outcome in ELBW preterms fed with human milk and extra
      protein supplementation as routine practice: do we need further evidence?
AB  - Extremely-low-birth-weight infants (ELBW) should be given nutrients to enable
      them to grow at the same rate as foetuses of the same gestational age, and lean
      body components, particularly the brain, are dependent on protein intake.
      Fortified human milk remains the best food for these preterms. Two groups of
      preterm infants weighing 580-1250 g and with a gestational age of 23-32 weeks
      were fed with different protein intakes in fortified human/maternal milk (3.5 g
      kg(-1) per day and 4.8 g kg(-1) per day in the control and extra-protein groups,
      respectively). The tolerance, intrahospital growth, neurological outcome and
      anthropometric data until 9 months corrected age were evaluated. The extra
      protein regime showed an intrahospital growth advantage (mostly in growth of head
      circumference, p 0.02, and length, p 0.04) only in the preterms weighing 580-980
      g and aged 23-30 weeks. In the same preterms, the Griffith Development Mental
      Score at 3 months corrected age showed higher scores than in the control group (p
      0.04). Growth during the post-discharge period for the experimental group at 9
      months corrected age showed mean z-score values for length higher than those in
      the control group (p 0.04).

PMID- 22958025
TI  - Human milk, a concrete risk for infection?
AB  - Breastfeeding should be considered a public health issue and the reference
      normative standards for infant feeding at least to the 6th month of life, with
      continuation of breastfeeding for 1 year or longer as mutually desired by mother
      and infant. Numerous studies demonstrate that breastfeeding results in improved
      infant and maternal health. Moreover the reduction of the risk of severe
      retinopathy of prematurity, sepsis and necrotizing enterocolitis is particularly
      evident in preterm infants. There are a limited number of medical conditions in
      which breastfeeding is contraindicated, including some maternal infectious
      diseases. During breastfeeding the baby can be infected by mother's pathogens
      with several routes of transmission that can be considered, such as respiratory
      secretions and droplets (e.g. Adenovirus, Influenza virus, Respiratory Syncytial
      Virus, Haemophilus, Mycoplasma) direct contact with lesions in the breast and
      nipple (e.g. HSV 1-2, VZV, Treponema) and breast milk. Frequently, in case of
      infection, different routes of transmission are contemporary implicated. The
      basic assumption is that breastfeeding is rarely contraindicated during maternal
      infections, a few exceptions are HTVL-I and HIV in industrialized country. The
      theoretic risk for transmission trough breast milk should be discussed and
      balanced with the benefits of breast milk, so the mother and parents can make an
      informed decision concerning infant feeding.

PMID- 22958026
TI  - Drugs and breastfeeding: instructions for use.
AB  - It's universally well known that breastfeeding, due to its numerous beneficial
      effects on child and maternal health, is the best feeding method for infants. The
      use of medication by the nursing mother and the physician's advice to stop
      nursing are the most common reasons for the cessation of breastfeeding. The
      physician plays an extremely delicate role and should be able to assess risks and
      benefits for both mother and child. The issue of which drugs are safe to take
      during lactation is quite complicated. Three main factors must be taken into
      account: pharmacokinetics, assessment of the risk to the infant and to the
      lactation. Excellent sources of reliable information are the reference books. For
      the most up-to-date information it would be useful to consult the online medical
      literature. Few drugs have been demonstrated to be absolutely contraindicated
      during breastfeeding. Clear, safe and reliable information is still lacking for
      most drugs. It would be desirable to see an improvement in knowledge about
      mechanisms for transfer of drugs into milk, to analyze the biotransformation
      process for a given drug and to study the clinical consequences of infant
      exposure to drugs present in milk.

PMID- 22958027
TI  - Breastfeeding policies and breastfeeding support programs in the mother's
      workplace.
AB  - Women should never be forced to make a choice between mother-work and other work.
      Many women mistakenly think they cannot breastfeed if they plan to return to
      work, and thus they may not talk with their employers about their intention to
      breastfeed or how breastfeeding might be supported at their workplace. All
      breastfeeding policies and strategies underline the importance of providing
      support for lactating mothers and highlight the need to promote specific
      interventions in the workplace. Possible strategies for working mothers include
      having the mother keep the baby with her while she works, allowing the mother to
      go to the baby to breastfeed during the workday, telecommuting, offering flexible
      work schedules, maintaining part-time work schedules, and using on-site or nearby
      child care centres.

PMID- 22958028
TI  - Ontogeny and drug metabolism in newborns.
AB  - In pediatric age and particularly in newborn infants the drug efficacy and safety
      are influenced by the growth and development on drug Absorption, Distribution,
      Metabolism and Excretion (ADME). Thanks to the fast development of
      pharmacogenomics and pharmacogenetics, the drug therapy promises to be adapted to
      the genetic profile of the individual, reducing considerably the side effects of
      drugs and increasing their efficacy. Interindividual variability in drug response
      is well known in both adults and children. Such a variability is multifactorial
      considering both intrinsic and extrinsic factors. Drug distribution in the
      neonate is influenced by a variety of age-dependent factors as a total body water
      content and distribution variations, role of drug transporters, blood/tissue
      protein binding, blood and tissue pH and perfusion. The development of enzymes
      involved in human metabolism were classified in 3 categories: 1) those expressed
      during the whole or part of the fetal period, but silenced or expressed at low
      levels within 1-2 years after birth; 2) those expressed at relatively constant
      levels throughout fetal development, but increased to some extent postnatally;
      and 3) those whose onset of expression can occur in the third trimester, but
      substantial increase is noted in the first 1-2 years after birth. Besides this
      intrinsic aspects influencing pharmacokinetics during the neonatal period there
      are other important events such as inborn or acquired diseases, environment and
      finally pharmacogenetics and pharmacogenomics. Thousands of deaths every years
      are caused by fatal drug reactions; among the potential causes there are not only
      the severity of the disease being treated, drug interactions, nutritional status,
      renal and liver functions, but also the inherited differences in drug metabolism
      and genetic polymorphism. Adverse drug reactions (ADRs) among pediatric patients
      have been shown to be three times more frequent than in adults. On August 2010
      The National Institute of Child Health and Human Development (NICHD) addressed
      patient safety issues in the NICU, recognizing that to understand and prevent
      adverse events, systematic research and education in safety issues needed. From
      all these concepts in terms of ADME, pharmacogenetics (relative to a single gene)
      and pharmacogenomics (relative to many genes) it is becoming more evident the
      perspective of the new concept of individualized medicine. The goal of this
      should be to identify which group of patients responds positively, which patients
      are nonresponders and who experiences adverse reaction for the same drug and
      dose. The interindividual variability in response to any drug is mostly dependent
      on DNA sequence variations across the human genome, the haplotype map (HAPMAP).
      At present there is still a big distance beween the knowledge in genetic and the
      practical application to model the drug profile to the genetic/genomic profile of
      the single patient. In the neonatal period the effects of growth in the
      pharmacodynamic, processes can help optimizing the dosage of neonatal frequently
      used medicines, thereby, minimizing their toxicity and increasing their efficacy.
      It should be useful to create accurate dosage adjustments according to the week
      of development.

PMID- 22958029
TI  - Inhibitors of gastric acid secretion drugs increase neonatal morbidity and
      mortality.
AB  - AIMS: To analyze all evidence on the possible increase in morbidity and mortality
      determined by the use of inhibitors of gastric acid secretion (IGAS) drugs.
      MATERIALS AND METHODS: We review all evidence exploring the adverse events
      associated with IGAS use in neonates. RESULTS: Despite being prescribed in an off
      label manner because of the perceived safety and potential benefit demonstrated
      for older populations, IGAS are being increasingly used in the neonatal period
      with much evidence derived from adults and children. Few data are available for
      neonates and indicate an association between IGAS use with infections and
      necrotizing enterocolitis (NEC), and with an increased mortality. Delayed gastric
      emptying, increased gastric mucus viscosity, modification in microbiota, and
      impairment of neutrophils functions are possible mechanisms of adverse events
      associated with IGAS use. CONCLUSIONS: A careful prescription of IGAS is crucial
      in order to reduce iatrogenic damage in neonates.

PMID- 22958030
TI  - Analgesic and sedative drugs in newborns requiring respiratory support.
AB  - Infants receiving respiratory assistance may feel pain due to underlying disease
      or ventilation itself. Pain control during neonatal respiratory care reduces
      morbidity. This article summarizes the main scientific evidence about the use of
      drugs during ventilatory assistance, and provides some practical suggestions on
      pain management in neonates with respiratory support.

PMID- 22958031
TI  - Medication errors in the neonate.
AB  - Critically ill patients are a high risk population for medication errors and
      neonates represent a more vulnerable group. Errors can occur in each step of the
      path from prescription to administration and their rate varies widely due to the
      error definition and identification methods used in the different studies.
      Identifying medication errors is a challenge in neonatal care and should be a
      priority among care-givers in order to prevent future incidents and to improve
      patient safety.

PMID- 22958032
TI  - Therapeutic hypothermia in the prevention of hypoxic-ischaemic encephalopathy:
      new categories to be enrolled.
AB  - Therapeutic hypothermia is now the standard of care for brain injury control in
      term infants with perinatal hypoxic ischemic encephalopathy (HIE). Accumulated
      evidence shows a reduction in mortality and long-term neurodevelopmental
      disability at 12-24 months of age, with more favourable effects in the less
      severe forms of HIE. Only few trials recruited newborns <36 weeks gestational
      age, or mild-to-moderate encephalopathy with base deficit (BD) <16. The new
      categories of patients to be enrolled should include (late) preterm infants,
      neonates with unexpected postnatal collapse, and newborns with stroke. Preterm
      HIE: Therapeutic hypothermia shows a good safety profile in clinical studies, and
      no adverse effects were noted in the preterm fetal animal model. Recently, it has
      been shown that mild hypothermia in preterm newborns with necrotizing
      enterocolitis (NEC) and multiple organ dysfunction syndrome (MODS) does not
      increase mortality, bleeding, infection, or need for inotropes in cooled
      newborns. A pilot study (NCT00620711) is currently recruiting newborns of > 32
      but < 36 weeks gestation with standard criteria for HIE. Postnatal Collapse: The
      postnatal collapse (PNC) is a rare (0.03-0.5/1000 live births) but life
      threatening hypoxic-ischemic event. No clinical trials of therapeutic hypothermia
      have specifically addressed to PNC. Nevertheless, a beneficial effect of brain
      cooling is expectable, and it has been proposed to include in brain hypothermia
      trials the infants with PNC fulfilling the entry criteria for HIE. Stroke:
      Perinatal arterial ischemic stroke is the most common cause of cerebral palsy
      (CP) in term and near-term newborn. In a systematic review and meta-analysis of
      animal studies of focal cerebral ischemia, hypothermia reduced the infarct size
      by 44%. No specific neuroprotective interventions are available for the
      management of acute perinatal stroke. Hypothermia may decrease seizures in
      newborns with encephalopathy and a focal infarct, potentially improving the long
      term outcome for these infants. CONCLUDING REMARKS: Future studies of therapeutic
      hypothermia should include the categories of newborns excluded from the published
      clinical trials, that is infants <36 weeks gestation, PNC or stroke, or admitted
      outside of the established 6-hour window, and with encephalopathy not imputable
      to HIE. New entry criteria will allow significant number of newborns to benefit
      from the treatment.

PMID- 22958033
TI  - Cerebral and somatic rSO2 in sick preterm infants.
AB  - Near infrared spectroscopy (NIRS) measures the regional tissue oxygen saturation
      (rSO2) of various organs and provides a reflection of the balance between tissue
      oxygen supply and demand. Oxymetry assessed via NIRS has been proposed as a
      'standard of care' and today it is already widely used in the NICU. This approach
      allows detection of any acute change in cerebral haemodynamics and continuous
      monitoring of cerebral and somatic oxygenation. This work describes three
      clinical cases of preterm VLBW infants which showed special points of interest
      during both cerebral and somatic NIRS monitoring.

PMID- 22958034
TI  - Biomarkers of brain damage in preterm infants.
AB  - OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early
      detection of preterm infants at risk for brain damage. However, among different
      tools Activin A, S100B protein and adrenomedullin assessment offer the
      possibility to investigate brain/multiorgan function and development. This could
      be especially useful in perinatal medicine that requires even more non-invasive
      techniques in order to fulfill the minimal handling in diagnostic and therapeutic
      strategy performance. MATERIALS AND METHODS: The concept of Unconventional
      Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards
      the assessment in non-invasive biological fluids of biochemical markers involved
      in the cascade of events leading to brain damage. RESULTS: Activin A, S100B
      protein and adrenomedullin in UBF were increased in preterm newborns developing
      brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers
      an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF
      as brain damage markers. The findings open a new cue on the use of these markers
      in daily neonatal intensive care unit (NICU) activities.

PMID- 22958035
TI  - Neuroprotective role of erythropoietin in neonates.
AB  - This review summarizes target populations of neonates for which erythropoietin
      (Epo) neuroprotective therapy might be of benefit, and the mechanisms by which
      Epo functions as a neuroprotective agent. Potential risks of Epo are reviewed.
      Finally, the progression of Epo neuroprotection from preclinical studies to
      translational studies is discussed.

PMID- 22958036
TI  - SpO2 and retinopathy of prematurity: state of the art.
AB  - AIM: To evaluate the relationship between arterial saturation values determined
      by pulse oximetry in the first weeks of life on the incidence of retinopathy of
      prematurity (ROP). METHODS: Randomized and observational studies were sought that
      compare the incidence of ROP in babies with high or low oxygen saturation
      targeting assisted by pulse oximetry. RESULTS: Over the last 15 years, evidence
      from experimental models of ROP and clinical studies, albeit not randomized
      trials, has shown a reduction in the incidence of ROP and other neonatal
      morbidities when very preterm newborns were targeted to a lower level of arterial
      oxygen saturation during their hospitalization, particularly in the first few
      weeks after birth. More recent evidence from randomized controlled trials
      confirms that targeting to a lower vs higher level of oxygenation from birth to
      36 weeks postmenstrual age (PMA) or to hospital discharge reduces the incidence
      of ROP requiring treatment by 50% but is correlated with higher mortality rates.
      CONCLUSION: Future randomized, controlled trials should be designed including a
      cohort of infants in which a more dynamic approach to saturation targeting is
      adopted, i.e. lower saturation levels in the first few weeks of life and higher
      saturation levels after the 32 weeks of PMA.

PMID- 22958037
TI  - Detecting permanent hearing loss in newborns.
AB  - From year 2003, the UNHS nationwide survey was commenced in Italy by the Italian
      Institute of Social Medicine, and was conducted in all Italian maternity
      hospitals in 2003, 2006 and 2008. All maternity wards active in Italy were
      included. RESULTS: Our study showed that the coverage and penetration of the UNHS
      programmes in Italy has increased from 2003 to 2008. At the end of 2008, 324,537
      newborns (60.6% of the total) were screened in Italian maternity hospitals. The
      referral rate before discharge varied from 2.6 to 16.7%, and this situation is
      reflected in a significant increase in costs. CONCLUSIONS: Considering the high
      cost of audiological confirmation, the first objective is to reduce the number of
      referred cases (false positives), by improving the training of screening
      personnel. In addition, close cooperation between audiological centres and
      maternity units and a dedicated secretariat team are important in increasing the
      efficacy of universal hearing screening. The investment in prevention will be
      repaid many times over.

PMID- 22958038
TI  - How to motivate newborn hearing screening in the absence of a national programme:
      a collaboration between parents and professionals.
AB  - The establishment of the Italian Pediatric Federation Newborn Hearing Screening
      Network and the Italian Society of Neonatology Infant Hearing Study Group is the
      result of an international collaboration between Parents and Medical
      Professionals in order to promote an effective model in developing Early Hearing
      Detection Intervention Programs that recognize the role of parents as partners in
      the process.   Among other factors, one important component frequently
      underestimated in most early intervention programs, both in the USA and other
      countries, involves the role of parental involvement within the Early Hearing
      Detection Intervention (EHDI) process. When a parent receives the news of their
      child's hearing loss, reactions may include, but are not limited to denial,
      grief, guilt, shame, fear and impotency. A parent may begin to ask certain
      questions: How do we know if the professionals in our children's lives are
      capable, educated, trained, up to date in their chosen fields of expertise? Do
      they respect our children and us as parents? Do they understand the needs of
      children who are deaf or hard of hearing? A life-long health professional -
      parental collaboration begins at the moment of the diagnosis of that child.  
      When analyzing the habilitation process of a deaf child, the relationship between
      health professionals and the crucial role of parents in raising that child is a
      50-50 shared responsibility. An objective of EHDI programs must be to empower
      parents by providing support from the beginning of the process. Distributing
      informative literature regarding the newborn hearing screening process and
      providing parents with access to resources such as parental support groups upon
      diagnosis equips parents with the tools necessary to immediately begin advocating
      for their children. The Italian Federation Pediatric Audiology Network was
      created by combining the parental perspective and medical protocols in order to
      establish the roots for stronger EHDI programs.

PMID- 22958039
TI  - Neonatal hyperbilirubinaemia: time for Italian recommendations?
AB  - The introduction of effective therapies for hyperbilirubinemia might have led to
      a general overconfidence among neonatal healthcare providers. National guidelines
      have been issued in many countries though they hardly stand the challenge of
      evidence-based medicine. A comparative appraisal shows significant discrepancies
      among different documents. As new, compelling evidence sheds a different light on
      bilirubin toxicity, this heterogeneity that borders confusion should be solved by
      implementing both clinical and basic research on the complex issue of neonatal
      hyperbilirubinemia.

PMID- 22958040
TI  - The Italian Registry of kernicterus and hyperbilirubinaemia.
AB  - AIM: to monitor the incidence of cases of kernicterus and severe
      hyperbilirubinemia in Italy over time, and to describe each single registered
      event with sufficient information in order to identify one or more possible
      failures in the management of jaundice. METHODS: the Task Force on
      hyperbilirubinemia of the Italian Society of Neonatology will draw up national
      guidelines for management of jaundice in the newborn and a national registry of
      kernicterus and hyperbilirubinemia for newborns with a gestational age greater
      than 34. RESULTS AND CONCLUSIONS: the choice of the inclusion criteria for the
      registry and the minimum information necessary to describe each single event
      registered are reported and will be discussed at the national congress of the
      Italian Society of Neonatology next October 2012.

PMID- 22958041
TI  - RDDR: a dysmorphology diagnostic network for newborns in central Italy.
AB  - In 2011, the RDDR network was developed in central Italy to provide support in
      the diagnosis of dysmorphic newborns. RDDR has been developed as an online
      electronic system that currently links 20 neonatology centres in central Italy,
      representing the submitting nodes that transmit patient clinical histories and
      the relevant photographical documentation to the software, which is password
      protected. Accepted cases appropriate for the RDDR are reviewed by the RDDR's
      dysmorphology experts who, through a forum section, provide diagnostic
      suggestions and recommendations for further investigation and patient management.
      Their remarks are summarised in clinical expert reports and sent to the
      submitting nodes. The results of the first 22 submitted cases are reviewed in
      this paper. The RDDR was developed on the basis of a related European tool,
      Dyscerne, a network of centres of expertise for dysmorphology.

PMID- 22958042
TI  - Chromosomal microarray (CMA) analysis in infants with congenital anomalies: when
      is it really helpful?
AB  - BACKGROUND: Birth defects are very common, affecting two to three infants in
      every 100 births, and often represent a diagnostic and management challenge. The
      birth of a child with multiple malformations is the beginning of a complex
      diagnostic process, where the primary purpose is to determine a precise
      nosological definition. An accurate diagnosis is a key prerequisite in providing
      a care plan, a prognosis and genetic counselling. The poor specificity of birth
      defects, the aetiology and course of which can vary despite similar phenotypic
      patterns, often makes the diagnostic path problematic. The advent and application
      of high-resolution chromosomal microarray, encompassing array-based comparative
      genome hybridization and single-nucleotide polymorphism arrays, has led to the
      detection of genomic copy-number abnormalities in patients affected by multiple
      congenital anomalies, dysmorphisms, developmental delay and mental retardation,
      but who have a normal karyotype. AIM: We discuss current guidelines and
      recommendations for chromosomal microarray use and how its application can help
      clinicians make accurate diagnoses in order to appropriately manage and treat
      affected newborns. CONCLUSIONS: Current guidelines strongly support the
      application of chromosomal microarray analysis as a first-tier cytogenetic
      diagnostic test alternative to karyotyping for patients with multiple congenital
      anomalies, or developmental delay, intellectual disability and autism spectrum
      disorders.

PMID- 22958043
TI  - Genetic predisposing factors to bronchopulmonary dysplasia: preliminary data from
      a multicentre study.
AB  - Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in
      preterm newborn infants. It is a multifactorial disease caused by the interaction
      between environmental and genetic factors. The aim of this study is to identify
      genetic variants contributing to BPD development using next-generation sequencing
      (NGS) technology. We prospectively evaluated 378 premature newborn infants with a
      gestational age <32 weeks in a multicentre study from 12 Italian neonatal
      intensive care unit from 2009 to 2012. Infants were divided into two groups:
      normal controls (225) and BPD-affected infants (141) with mild (65, 46.1%),
      moderate (40, 28.4%) and severe (36, 25.5%) BPD. BPD was more frequent in infants
      with lower weight and gestational age. Antenatal steroid administration was more
      frequent in the control group. Postnatal infection, respiratory distress
      syndrome, patent ductus arterious, cerebral haemorrhage, surfactant
      administration, ventilatory support, diuretics and postnatal steroid
      administration correlated with severity of BPD. Among BPD, moderate and severe
      cases will be selected as BPD "extreme phenotypes", and in fact variations in 28
      day oxygen need-based BPD were previously shown to be fully attributable to
      environmental effects whereas dependence on supplemental oxygen at 36 weeks seems
      to better reflect underlying genetic susceptibility. Exome analysis by NGS is in
      progress. Identifications of genetic markers predisposing to BPD may allow
      development of personalized and preventive treatments.

PMID- 22958044
TI  - Genetic polymorphisms of antioxidant enzymes in preterm infants.
AB  - BACKGROUND: Oxidative stress (OS) is significantly involved in the development of
      several complications associated with preterm birth, such as respiratory distress
      syndrome (RDS), bronchopulmonary dysplasia (BPD), retinopathy of prematurity
      (ROP) and intraventricular hemorrhage (IVH). Evidence is growing about the
      associations between single nucleotide polymorphisms (SNPs) in genes involved in
      OS or antioxidant response and the occurrence of neonatal morbidities. AIM OF THE
      STUDY: To assess whether SNPs in genes of superoxide dismutase (SOD) and catalase
      (CAT), involved in antioxidant pathways, correlate with the occurrence of RDS,
      BPD, IVH and ROP in preterm neonates. METHODS: We performed a retrospective study
      involving neonates <28 weeks of gestational age. RESULTS: We demonstrated that
      rs8192287 SOD3 polymorphism is an independent protective factor for IVH, while
      rs4880 and rs5746136 SOD2 polymorphisms are associated with lower gestational age
      and birth weight. Haplotypes reconstruction showed that SOD1 (GG) decreased the
      risk of RDS, IVH and ROP; SOD2 (GT) increased the risk of BPD and decreased the
      risk of RDS, IVH, and ROP; SOD3 (TGC) decreased the risk of BPD and IVH; and CAT
      (CTC) decreased the risk of RDS. CONCLUSIONS: The study of SNPs or haplotypes
      reconstruction in genes involved in OS or scavenging activity may be helpful in
      identifying preterm newborns with a particularly high risk of morbidities, who
      may benefit from specific prevention strategies.

PMID- 22958045
TI  - The role of immunohistochemistry in the study of the newborn kidney.
AB  - The identification of the different cell types involved in human nephrogenesis,
      when solely based on morphology, may lead to errors in its interpretation, given
      the complexity of the histological picture of the fetal and of the newborn
      kidney. In this study, the most recent works utilizing immunohistochemistry for
      the identification of the multiple cell types involved in human nephrogenesis are
      reviewed. The role of WT1, MUC1, Thymosin beta 10, Thymosin beta 4, CD10 and CD44
      in the different phases of glomerulogenesis and of tubulogenesis is here
      described, with particular emphasis on their expression in the early phases of
      nephrogenesis. On the basis of our data, immunohistochemistry appears to be a
      useful tool in the study of human nephrogenesis, giving new data on the different
      steps of the differentiation of metanephric mesenchyme towards the multiple cell
      types characterizing the mature human kidney. Moreover, allowing a better
      knowledge of the protein products involved in the generation of new nephrons,
      immunohistochemistry could open new perspectives in the field of renal
      regenerating medicine, evidencing the factors able to prolong nephrogenesis after
      birth, helping us to reach our goal: allowing newborn kidneys to restore their
      nephron endowment, escaping susceptibility to hypertension and renal disease in
      adulthood.

PMID- 22958046
TI  - aEEG in preterm infants.
AB  - Over the last decade, the survival of premature babies has improved dramatically.
      Such infants, especially those with extremely low birth weight, are still
      affected by dangerous complications occurring during the neonatal period that
      often cause brain damage. Intraventricular-intraparenchymal haemorrhage (IVH
      IPH), periventricular leukomalacia (PVL), seizures, meningitis and hypoxic
      ischaemic encephalopathy are the most common complications. Such problems require
      more specialized monitoring of brain function during this critical period. In
      recent years, many studies on very premature infants have shown that aEEG has a
      high predictive value for both short-term and long-term outcome. In fact, it has
      been proven that some types of background activity patterns, the absence of a
      sleep-wake cycle, and seizure activity are related to the onset of early
      complications such as IVH-IPH and PVL. Most recent studies have shown that an
      aEEG performed in the early hours or during the first days of life can predict
      the neurobehavioural development of preterm infants at 2 years and 3 years
      (Bayley Scale). In particular our study demonstrates that loss of sleep-wake
      cycling, shown by aEEG, has a high positive predictive value for the development
      of posthaemorrhagic hydrocephalus (PPH) in preterm infants with IVH; therefore,
      the study of cerebral background activity and in particular of sleep-wake cycling
      can be used as an early prognostic tool in patients at risk of PPH.

PMID- 22958047
TI  - Mandibular distraction osteogenesis for neonates with Pierre Robin sequence and
      airway obstruction.
AB  - Neonates with Pierre Robin Sequence (PRS) usually present with varying degrees of
      upper airway obstruction and difficulty feeding. Early treatment is important for
      such children in order to prevent impaired cognitive development resulting from
      hypoxemic episodes. Various procedures aimed at widening the pharyngeal space
      have been proposed, including prone position, tongue-lip adhesion, mandibular
      traction, non-invasive ventilation and palatal plates. Mandibular distraction
      osteogenesis (MDO) using external or internal devices has become increasingly
      popular as an alternative treatment option when other medical or surgical
      techniques do not prove to be satisfactory. This review summarizes current
      evidence on the effectiveness of MDO in infants with PRS. Because of a lack of
      studies comparing this treatment with other procedures, general recommendations
      cannot be drawn and treatment of infants with PRS still requires
      individualization.

PMID- 22958048
TI  - Foetal and neonatal stress.

PMID- 22958049
TI  - Painful procedures in the NICU.
AB  - The authors after a brief introduction on the development of the perception of
      pain in the fetus and newborn, focus attention on the problem of painful
      procedures that are performed in the neonatal intensive care units reported in
      the scientific literature. Then report the design of the double-blind study that
      is taking place from February 2012 at the NICU ARNAS Civic - Palermo using three
      different concentrations of sucrose as analgesia during venipuncture and heel
      puncture in term neonates.

PMID- 22958050
TI  - Pain management during invasive procedures at Italian NICUs: has anything changed
      in the last 5 years?
AB  - OBJECTIVE: To ascertain the extent to which neonatal analgesia for invasive
      procedures has changed in the last 5 years since the publication of Italian
      guidelines. METHODS: We compared survey data for the years 2004 and 2010 on
      analgesia policy and practices for common invasive procedures at Italian Neonatal
      Intensive Care Units (NICUs); 75 NICUs answered questionnaires for both years and
      formed the object of this analysis. RESULTS: By 2010, analgesia practices for
      procedural pain had improved significantly for almost all invasive procedures (p
      < 0.05), with both non-pharmacological and pharmacological methods being adopted
      by the majority of NICUs (unlike the situation in 2004). The routine use of
      medication for major invasive procedures was still limited, however (35% of
      lumbar punctures, 40% of tracheal intubations, 46% during mechanical
      ventilation). Postoperative pain treatment was still inadequate, and 41% of
      facilities caring for patients after surgery did not treat pain routinely. Pain
      monitoring had definitely improved since 2004 (p < 0.05), but not enough: only 21
      and 17% of NICUs routinely assess pain during mechanical ventilation and after
      surgery, respectively. CONCLUSION: There have been improvements in neonatal
      analgesia practices in Italy since national guidelines were published, but pain
      is still undertreated and underscored, especially during major invasive
      procedures. It is mandatory to address the gap between the recommendations in the
      guidelines and clinical practice must be addressed through with effective quality
      improvement initiatives.

PMID- 22958051
TI  - Primary assessment of a self-adhesive gutta-percha material.
AB  - AIM: To evaluate a prototype gutta-percha material (Bio-Gutta), which is claimed
      to work without sealer because of its incorporated ultrafine bioactive glass
      particles, in terms of its induction of pH and calcium phosphate (CaP)
      precipitates, and its self-adhesiveness in root canals. METHODOLOGY: Bio-Gutta
      was compared with conventional gutta-percha (GP, composition: 70 wt% ZnO, 30 wt%
      polyisoprene). Test and control materials (N = 3) were immersed in phosphate
      buffered saline (PBS) at 37  degrees C for 30 days. The pH in the solution was
      monitored. Apparent CaP formation was assessed using scanning electron microscopy
      (SEM). The root canals of 33 single-rooted teeth were filled by vertical
      compaction of heated Bio-Gutta, 33 control canals were filled with vertically
      compacted GP without sealer. Push-out bond strengths associated with the filling
      materials in root cross-sections from middle root thirds was determined 1, 8, and
      30 days after root filling (N = 11 per group). These values were compared between
      groups using one-way anova (alpha < 0.05). RESULTS: Bio-Gutta induced a high pH
      in the PBS solution, which plateaued at values between 11.4 and 11.8. Apparent
      CaP crystals covered the Bio-Gutta material after 30 days of immersion in PBS,
      whilst no such structures were observed on GP. Both materials under investigation
      had similar initial push-out bond strength values (P > 0.05). The adherence of
      Bio-Gutta increased from day 1 to 8 and was significantly higher than that of
      conventional GP at 8 and 30 days (P < 0.05). CONCLUSIONS: The experimental gutta
      percha material under investigation was alkaline and caused CaP precipitates on
      its surface. It improved its adherence to the root canal wall within 1 week.

PMID- 22958052
TI  - The ARGA study with Italian general practitioners: prescriptions for allergic
      rhinitis and adherence to ARIA guidelines.
AB  - BACKGROUND: General practitioners (GPs) are the healthcare professionals to whom
      patients with rhinitis firstly refer for their symptoms. OBJECTIVE: In the
      present study, we assessed drug prescriptions for allergic rhinitis (AR) and
      evaluated prescriptive adherence to ARIA treatment guidelines. METHODS: Data on
      1379 AR patients were collected by 107 Italian GPs. Adherence to ARIA guidelines
      was evaluated according to AR severity classification. RESULTS: AR was diagnosed
      by GPs as mild intermittent for 46.2% of patients, mild persistent for 26.6%,
      moderate-severe intermittent for 20.2%, and moderate-severe persistent for 7%;
      43.7% of AR patients had concomitant asthma. The most frequently prescribed
      therapeutic groups were antihistamines (anti-H, 76%) and nasal corticosteroids
      (NCS, 46%). Anti-H were significantly used more often to treat AR alone than AR +
      asthma (85 vs. 68%, p < 0.001), whereas NCS were used more often to treat AR +
      asthma than AR alone (50 vs. 42%, p = 0.01). Among patients with only mild
      intermittent AR, 39% were prescribed combined therapy. Among patients with
      moderate-severe persistent AR, 30% of those with AR alone and 18% of those with
      AR + asthma were prescribed monotherapy based on anti-H. GPs were more compliant
      with ARIA guidelines while treating AR alone (57%) than AR + asthma (46%)
      patients. The adherence increased according to the severity grade and was
      satisfactory for moderate-severe persistent AR (89% for AR alone and 95% for AR +
      asthma). CONCLUSIONS: Adherence to ARIA guidelines is satisfactory only for
      treatment of more severe patients, thus GPs often tend to treat patients
      independently from ARIA guidelines. Since prescription data only provide limited
      information to judge prescribing quality, some deviation from the gold standard
      are to be expected.

PMID- 22958053
TI  - Non-alcoholic fatty liver disease (NAFLD) is associated with low level of
      physical activity: a population-based study.
AB  - BACKGROUND: High intensity exercise improves metabolic status and may potentially
      mobilise hepatic fat. AIM: To assess the level of physical activity (PA) of
      subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: Data were
      obtained from NHANES (2003-2006). Activity counts obtained from accelerometer
      readings (ActiGraph, Fort Walton Beach, FL), from 7 consecutive days quantified
      total PA and time spent engaged in different levels of activity. All measures
      were counts/minutes/day: (sedentary <100; light 100-0027; moderate, 2020-5999 and
      vigorous, 6000+). NAFLD was defined as a fatty liver index >60 (FLI) in the
      absence of other chronic liver disease. Subjects with NAFLD were compared to
      controls using stratum-specific Chi-squared and t-tests. Simple linear regression
      analyses (with Taylor series linearised variance estimation and weighting) were
      used to determine the association between PA levels and NAFLD. P-values <0.05
      were considered significant. Statistical analyses were conducted using sudaan
      version 10.1 and sas version 9.1. RESULTS: We included 3056 participants. NAFLD
      patients were older, had higher BMI, larger waist circumference, higher sum of
      skinfolds, more likely to have insulin resistance (HOMA > 3.0) and type-2
      diabetes (all P-values <0.01). Average PA for NAFLD subjects was about 28.7
      counts/minute/day less than controls (P < 0.01). Furthermore, NAFLD subjects
      spent less time participating in activity at any level (P < 0.01). Subjects with
      NAFLD and DM were in the lowest quartile of average PA as well as moderate
      vigorous PA (P < 0.01). CONCLUSIONS: Data from this study show that non-alcoholic
      fatty liver disease patients have low level of physical activity and, when they
      have diabetes mellitus, they perform at the lowest quartile of physical activity
      and moderate-vigorous physical activity.

PMID- 22958054
TI  - HRTEM of 1DSnTe@SWNT nanocomposite located on thin layers of graphite.
AB  - The method for imaging of highly sensitive nanostructures unstable under electron
      beam irradiation is introduced. To reduce charge and thermally generated beam
      damage, highly conductive multilayered graphene or thin graphite layers were used
      as supports for nanostructures. Well-defined crystalline structure of graphite
      layers enables image reconstruction by Fourier filtering and allows maintaining
      high quality of images. The approach was tested for imaging of highly sensitive
      quasi one-dimensional SnTe nanocrystals hosted inside single-walled carbon
      nanotubes. Relying on the filtered images and the image simulation, the structure
      of one-dimensional SnTe was established as a chain of fcc NaCl type unit cells,
      connected by the [001] edges with <110> direction coinciding with nanotube axis.

PMID- 22958056
TI  - Immunophenotyping of male breast cancer.
AB  - AIMS: Male breast cancer is a rare disease, and knowledge of carcinogenesis is
      limited. Conflicting results, based on small series, have been reported for
      clinically relevant biomarkers. METHODS AND RESULTS: One hundred and thirty-four
      cases of male breast cancer were immunohistochemically stained on tissue
      microarrays for oestrogen receptor (ER), progesterone receptor (PR), androgen
      receptor, human epidermal growth factor receptor 2 (HER2), BRST2, cyclin D1, bcl
      2, p53, p16, p21, Ki67, cytokeratin (CK) 5/6, CK14, and epidermal growth factor
      receptor. Data were correlated with clinicopathological features and patient
      outcome. High mitotic count and high grade were correlated with high Ki67, HER2
      amplification/overexpression, p53 accumulation, high p21 expression, low PR
      expression, and low bcl-2 expression. PR negativity (P=0.009) and p53
      accumulation (P=0.042) were correlated with decreased 5-year survival and were
      independent markers for patient outcome in Cox regression. In unsupervised
      hierarchical clustering, four groups were identified that were correlated with
      distinctive clinicopathological features. The hormone negative/ER-positive/high
      grade cluster was significantly associated with decreased survival (P=0.011) and
      was an independent prognostic factor in Cox regression. CONCLUSIONS: Several
      tissue biomarkers are associated with an aggressive phenotype in male breast
      cancer. PR and p53 are the most promising individual prognostic markers. On the
      basis of immunophenotype, four distinctive and prognostically relevant male
      breast cancer groups were identified, indicating that protein expression
      profiling may be clinically useful in male breast cancer.

PMID- 22958057
TI  - Nordic translations of the Manchester Clinical Supervision Scale: a rejoinder.

PMID- 22958055
TI  - An international pilot study of an Internet-based platform to facilitate clinical
      research in epilepsy: the EpiNet project.
AB  - PURPOSE: We created an epilepsy patient database that can be accessed via the
      Internet by neurologists from anywhere in the world. The database was designed to
      enroll and follow large cohorts of patients with specific epilepsy syndromes, and
      to facilitate recruitment of patients for investigator-initiated clinical trials.
      METHODS: The EpiNet database records physician-derived information regarding
      seizure type and frequency, epilepsy syndrome, etiology, drug history, and
      investigations. It can be accessed from any country by approved investigators via
      a secure, password-protected Website. All data are encrypted. The database is for
      both research and clinical purposes. Investigators were invited to register any
      patient with epilepsy, but were particularly encouraged to register patients when
      uncertain of the optimal management. Participation required approval from
      investigators' ethics committees and institutional review boards, and all
      patients or their caregiver provided written informed consent. Patients were not
      enrolled in clinical trials in this pilot study. KEY FINDINGS: The international
      pilot study recruited patients from September 2010 to November 2011. Sixty-four
      investigators or research assistants from 25 centers in 13 countries registered
      1,050 patients. Patients with a wide range of epilepsy syndromes and etiologies
      were registered. Patients' ages ranged from 2 weeks to 90 years. SIGNIFICANCE:
      The Website was successfully used by doctors working in different health systems.
      The pilot study confirmed that this low-cost, collaborative approach to research
      has great potential. Large, multicenter cohort studies will commence in 2012, and
      randomized clinical trials are being planned. All epileptologists are invited to
      join this project.

PMID- 22958058
TI  - Inhibitory effects of Citrus flavonoids on starch digestion and antihyperglycemic
      effects in HepG2 cells.
AB  - Flavonoids are a class of important bioactive natural products and are being
      extensively used in functional foods. In the present study, the effects of four 
      Citrus  flavonoids (i.e., hesperidin, naringin, neohesperidin, and nobiletin) on
      amylase-catalyzed starch digestion, major digestive enzyme activities (e.g.,
      pancreatic alpha-amylase and alpha-glucosidase), and glucose use in HepG2 cells
      were investigated. The results showed that all of the tested  Citrus  flavonoids
      significantly inhibited amylase-catalyzed starch digestion. Moreover, naringin
      and neohesperidin mainly inhibited amylose digestion, whereas hesperidin and
      nobiletin inhibited both amylose and amylopectin digestion. However, these
      flavonoids showed weak inhibitory activities against digestive enzymes.
      Furthermore, glucose consumption, glycogen concentration, and glucokinase
      activity were significantly elevated, and glucose-6-phosphatase activity was
      markedly decreased by  Citrus  flavonoids. These results demonstrate that  Citrus
      flavonoids play important roles in preventing the progression of hyperglycemia,
      partly by binding to starch, increasing hepatic glycolysis and the glycogen
      concentration, and lowering hepatic gluconeogenesis. This work suggests that 
      Citrus  flavonoids might be potentially used for the prevention of postprandial
      hyperglycemia.

PMID- 22958059
TI  - Non-invasive identification of melanoma with near-infrared and skin impedance
      spectroscopy.
AB  - BACKGROUND/PURPOSE: An early diagnosis of cutaneous malignant melanoma is of high
      importance for good prognosis. An objective, non-invasive instrument could
      improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies.
      The aim of this study was to investigate the use of Near-infrared and skin
      impedance spectroscopy in combination as a tool to distinguish between malignant
      and benign skin tumours. METHODS: Near-infrared and skin impedance spectra were
      collected in vivo on 50 naevi or suspect melanomas prior to excision. Received
      data were analysed using multivariate techniques and the results were compared to
      histopathology analyses of the tumours. A total of 12 cutaneous malignant
      melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study.
      RESULTS: The observed sensitivity and specificity of the proposed method were 83%
      and 95%, respectively, for malignant melanoma. CONCLUSION: The results indicate
      that the combination of near-infrared and skin impedance spectroscopy is a
      promising tool for non-invasive diagnosis of suspect cutaneous malignant
      melanomas.

PMID- 22958060
TI  - Language use in an internet support group for smoking cessation: development of
      sense of community.
AB  - The use of the internet for health purposes is increasing, as is the number of
      sites and online communities aimed at helping people to stop smoking. Some of the
      effects of online communities may be mediated through a sense of community. By
      using the computer-program Linguistic Inquiry and Word Count with a Norwegian
      dictionary, we investigated whether there was a development of sense of community
      in a forum related to a Norwegian smoking cessation intervention, by examining
      the use of self-referencing vs. collective referencing words. Data from a 4-year
      period, including in total 5242 web pages, were included. There was a significant
      increase in the use of collective words over time and a significant decrease in
      the use of self-referencing words. The increase in the use of collective words
      suggests that there appears to be a development of a sense of community in the
      forum over time. More research is needed to study the importance of an online
      sense of community.

PMID- 22958061
TI  - Quantitative analysis of intramolecular exciplex and electron transfer in a
      double-linked zinc porphyrin-fullerene dyad.
AB  - Photoinduced charge transfer in a double-linked zinc porphyrin-fullerene dyad is
      studied. When the dyad is excited at the absorption band of the charge-transfer
      complex (780 nm), an intramolecular exciplex is formed, followed by the complete
      charge separated (CCS) state. By analyzing the results obtained from time
      resolved transient absorption and emission decay measurements in a range of
      solvents with different polarities, we derived a dependence between the
      observable lifetimes and internal parameters controlling the reaction rate
      constants based on the semiquantum Marcus electron-transfer theory. The critical
      value of the solvent polarity was found to be epsilon(r) ~ 6.5: in solvents with
      higher dielectric constants, the energy of the CCS state is lower than that of
      the exciplex and the relaxation takes place via the CCS state predominantly,
      whereas in solvents with lower polarities the energy of the CCS state is higher
      and the exciplex relaxes directly to the ground state. In solvents with moderate
      polarities the exciplex and the CCS state are in equilibrium and cannot be
      separated spectroscopically. The degree of the charge shift in the exciplex
      relative to that in the CCS state was estimated to be 0.55 +/- 0.02. The
      electronic coupling matrix elements for the charge recombination process and for
      the direct relaxation of the exciplex to the ground state were found to be 0.012
      +/- 0.001 and 0.245 +/- 0.022 eV, respectively.

PMID- 22958062
TI  - Phacoemulsification versus manual small-incision cataract surgery for age-related
      cataract: meta-analysis of randomized controlled trials.
AB  - BACKGROUND: To compare outcomes of phacoemulsification (PE) with manual small
      incision cataract surgery (MSICS) for age-related cataract. DESIGN: Meta
      analysis. PARTICIPANTS: Patients from previously reported randomized controlled
      trials (RCTs) of PE and MSICS with clinical outcomes. METHODS: A comprehensive
      literature search of Cochrane Library, PubMed and EMBASE to identify relevant
      RCTs comparing PE and MSICS. A meta-analysis was performed on the results and a
      RevMan 5.0 software (version 5.0; Cochrane Collaboration, Oxford, UK) was used
      for data analysis. MAIN OUTCOME MEASURES: Primary outcome measures included best
      corrected vision acuity (BCVA), uncorrected visual acuity (UCVA). Secondary
      outcome measures included surgically induced astigmatism (SIA), percentage of
      endothelial cell count (ECC) loss and complications. RESULTS: Six RCTs describing
      a total of 1315 eyes were identified. There were no significant differences
      between the techniques regarding the BCVA 6/9 or better (P = 0.69) and less than
      6/18 (P = 0.68), percent of ECC loss (P = 0.45), intraoperative or postoperative
      complications (P = 0.44 and P = 0.87, respectively). However, a greater
      proportion of patients in the PE group had final UCVA >= 6/9 (P = 0.03), whereas
      a greater proportion of patients in the MSICS group had final UCVA < 6/18 (P =
      0.03). Moreover, PE group induced less SIA (P < 0.00001). CONCLUSIONS: PE is
      superior to MSICS in UCVA and causes less SIA, but there were no significant
      differences in visual rehabilitation, ECC loss and complication rates between the
      two techniques.

PMID- 22958063
TI  - Bullous eosinophilic cellulitis in a child treated with dapsone.
AB  - Eosinophilic cellulitis, or Wells syndrome, is a rare but well-described
      condition in which bullous lesions are uncommon, especially in childhood. We
      report a case of bullous eosinophilic cellulitis recalcitrant to steroid therapy
      in a 9-year-old boy who was successfully treated with oral dapsone. 

PMID- 22958064
TI  - Palladium-catalyzed alkyne insertion/Suzuki reaction of alkyl iodides.
AB  - A palladium-catalyzed alkyne insertion/Suzuki reaction with unactivated alkyl
      iodides is described. Under the reaction conditions, selective migratory
      insertion of alkynes avoids beta-hydride elimination and provides a facile
      synthesis of stereodefined, tetrasubstituted olefins. The transformation offers
      broad substrate scope for both the alkyl iodide and boron nucleophile.
      Mechanistic studies have revealed inversion of the stereocenter for the carbon
      bearing the iodide.

PMID- 22958066
TI  - Abstracts of the 16th Congress of the EFNS (European Federation of Neurological
      Societies). Stockholm, Sweden. September 9-10, 2012.

PMID- 22958065
TI  - Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two
      dimensional combinatorial screening.
AB  - There are many potential RNA drug targets in bacterial, viral, and human
      transcriptomes. However, there are few small molecules that modulate RNA
      function. This is due, in part, to a lack of fundamental understanding about RNA
      ligand interactions including the types of small molecules that bind to RNA
      structural elements and the RNA structural elements that bind to small molecules.
      In an effort to better understand RNA-ligand interactions, we diversified the 2
      aminobenzimidazole core (2AB) and probed the resulting library for binding to a
      library of RNA internal loops. We chose the 2AB core for these studies because it
      is a privileged scaffold for binding RNA based on previous reports. These studies
      identified that N-methyl pyrrolidine, imidazole, and propylamine diversity
      elements at the R1 position increase binding to internal loops; variability at
      the R2 position is well tolerated. The preferred RNA loop space was also
      determined for five ligands using a statistical approach and identified trends
      that lead to selective recognition.

PMID- 22958068
TI  - Potential errors and misuse of statistics in studies on leakage in endodontics.
AB  - AIM: To assess the quality of the statistical methodology used in studies of
      leakage in Endodontics, and to compare the results found using appropriate versus
      inappropriate inferential statistical methods. METHODOLOGY: The search strategy
      used the descriptors 'root filling' 'microleakage', 'dye penetration', 'dye
      leakage', 'polymicrobial leakage' and 'fluid filtration' for the time interval
      2001-2010 in journals within the categories 'Dentistry, Oral Surgery and
      Medicine' and 'Materials Science, Biomaterials' of the Journal Citation Report.
      All retrieved articles were reviewed to find potential pitfalls in statistical
      methodology that may be encountered during study design, data management or data
      analysis. RESULTS: The database included 209 papers. In all the studies reviewed,
      the statistical methods used were appropriate for the category attributed to the
      outcome variable, but in 41% of the cases, the chi-square test or parametric
      methods were inappropriately selected subsequently. In 2% of the papers, no
      statistical test was used. In 99% of cases, a statistically 'significant' or 'not
      significant' effect was reported as a main finding, whilst only 1% also presented
      an estimation of the magnitude of the effect. When the appropriate statistical
      methods were applied in the studies with originally inappropriate data analysis,
      the conclusions changed in 19% of the cases. CONCLUSIONS: Statistical
      deficiencies in leakage studies may affect their results and interpretation and
      might be one of the reasons for the poor agreement amongst the reported findings.
      Therefore, more effort should be made to standardize statistical methodology.

PMID- 22958070
TI  - Mosquito vectors survey in the AL-Ahsaa district of eastern Saudi Arabia.
AB  - The present study aimed to identify the mosquito vectors distributed throughout
      AL-Ahsaa district situated in the eastern region of Saudi Arabia. Mosquito larvae
      were collected seasonally for one year (October 2009 to September 2010) from
      different breeding sites in seven rural areas utilizing long aquatic nets.
      Salinity and pH of these breeding sites were also measured seasonally. The survey
      revealed the presence of five mosquito species, Aedes caspius Pallas (Diptera:
      Culicidae), Anopheles multicolor Cambouliu, Culex perexiguus Theobald, Culex
      pipiens L., and Culex pusillus Macquart, representing three genera; four of them
      (Ae. caspius, An. multicolor, Cx. perexiguus, and Cx. pipiens) are important
      vectors of diseases. Ae. caspius is the most common vector followed by Cx.
      pipiens and then Cx. perexiguus. Mosquitoes in AL-Ahsaa are prevalent in both
      winter and spring seasons, rarely encountered in summer, and are found in
      moderation during the autumn months. These results are compared with results of
      other regions in the Kingdom of Saudi Arabia.

PMID- 22958071
TI  - Thermophilic enrichment of microbial communities in the presence of the ionic
      liquid 1-ethyl-3-methylimidazolium acetate.
AB  - AIMS: The aim of the study was to develop an approach to enrich ionic liquid
      tolerant micro-organisms that efficiently decompose lignocellulose in a
      thermophilic and high-solids environment. METHODS AND RESULTS: High-solids
      incubations were conducted, using compost as an inoculum source, to enrich for
      thermophilic communities that decompose switchgrass in the presence of the ionic
      liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]). Ionic liquid levels
      were increased from 0 to 6% on a total weight basis incrementally. Successful
      enrichment of a community that decomposed lignocellulose at 55 degrees C in the
      presence of 6% [C2mim][OAc] was achieved, when the [C2mim][OAc] level was
      increased stepwise from 2% to 4% to 5% to 6%. Pyrosequencing results revealed a
      shift in the community and a sharp decrease in richness, when thermophilic
      conditions were applied. CONCLUSIONS: A community tolerant to a thermophilic,
      high-solids environment containing 6% [C2mim][OAc] was enriched from compost.
      Gradually increasing [C2mim][OAc] concentrations allowed the community to adapt
      to [C2mim][OAc]. SIGNIFICANCE AND IMPACT OF THE STUDY: A successful approach to
      enrich communities that decompose lignocellulose under thermophilic high-solids
      conditions in the presence of elevated levels of [C2mim][OAc] has been developed.
      Communities yielded from this approach will provide resources for the discovery
      of enzymes and metabolic pathways relevant to biomass pretreatment and fuel
      production.

PMID- 22958072
TI  - Clinical value of paraffin sections in association with Mohs micrographic surgery
      for nonmelanoma skin cancers.
AB  - BACKGROUND: During Mohs micrographic surgery (MMS), situations can arise in which
      paraffin sections may be used in conjunction with frozen sections. OBJECTIVE: To
      determine the clinical value of paraffin sections in association with MMS,
      including frequency, reasons, and information obtained. METHODS AND MATERIALS:
      Single-center retrospective cohort study at a cancer center. MMS cases for
      nonmelanoma skin cancers over a 5-year period in which paraffin sections were
      used were identified. Reasons for submitting paraffin sections were reviewed.
      Initial biopsy, Mohs frozen section, and paraffin section diagnoses and
      histologic subtypes were compared. RESULTS: In 258 (7.8%) cases, paraffin
      sections were used in association with MMS. The most common reasons were to
      further assess high-risk histologic features or unusual frozen section findings,
      to complete tumor staging of cutaneous squamous cell carcinomas, and to assess
      perineural invasion (PNI). Initial biopsy diagnosis differed from the Mohs frozen
      and paraffin section diagnoses in 20% to 22% of cases. The initial biopsy
      histologic subtype changed from low or indeterminate to high risk in Mohs frozen
      and paraffin sections in 24% to 29% of cases. CONCLUSION: In MMS for select high
      risk or unusual nonmelanoma skin cancers, paraffin sections are useful in more
      accurately documenting tumor histology, completing cutaneous squamous cell
      carcinoma staging, and detecting PNI.

PMID- 22958073
TI  - Leptomeningeal spinal metastases from glioblastoma multiforme: treatment and
      management of an uncommon manifestation of disease.
AB  - Glioblastoma multiforme (GBM) is one of the most common and aggressive primary
      brain tumors, composing 12%-20% of all intracranial tumors in adults. Average
      life expectancy is merely 12-14 months following initial diagnosis. Patients with
      this neoplasm have one of the worst 5-year survival rates among all cancers
      despite aggressive multimodal treatment consisting of maximal tumor resection,
      radiation therapy, and adjuvant chemotherapy. With recent advancements in
      management strategies, there has been improvement in the overall trend in patient
      outcomes; however, recurrence remains nearly inevitable. While most tumors recur
      locally, metastases to distal locations have become more common. Specifically,
      the last decade has seen an increased incidence of spinal metastases,
      representing an emerging complication in patients with intracranial GBM. However,
      the literature regarding prevention strategies and the presentation of spinal
      metastases has remained scarce. As local control of primary lesions continues to
      improve, more cases of spinal metastases are likely to be seen. In this review
      the authors present a new case of metastatic GBM to the L-5 nerve root, and they
      summarize previous cases of intracranial GBM with leptomeningeal spinal
      metastatic disease. They also characterize key features of this disease
      presentation and discuss areas of future investigation necessary for enhanced
      prevention and treatment of this complication.

PMID- 22958074
TI  - Epidural neural fibrolipoma of the thoracic vertebral canal.
AB  - Neural fibrolipoma is a benign tumor that most frequently infiltrates the median
      nerve. The authors describe a patient with spinal cord compression syndrome
      caused by a neural fibrolipoma. The tumor originated in the thoracic nerve at the
      T6-7 extradural level in the left conjugate foramen and extended into the
      thoracic cavity. Total removal was achieved by a combined posterior and
      costotransversectomy approach. Postoperatively, the patient's spinal cord
      compression syndrome resolved. No tumor recurrence has been observed in medium
      term follow-up. This is the second case of an extradural spinal neural
      fibrolipoma to be reported in the literature.

PMID- 22958076
TI  - Pharmacokinetics and hematotoxicity of a novel copper-based anticancer agent:
      casiopeina III-Ea, after a single intravenous dose in rats.
AB  - Casiopeina III-Ea is a mixed chelate copper (II) complex that has shown cytotoxic
      and antitumor activity in vitro and in vivo. The aim of this study was to
      investigate the pharmacokinetics of total copper derived from casiopeina III-Ea
      administered by intravenous bolus injection to Wistar rats. Other objective was
      to evaluate the hematotoxicity produced by this compound in those animals. Wistar
      rats received a single intravenous dose of 4 mg/kg of casiopeina III-Ea. Blood
      samples were taken and pharmacokinetics evaluated. Furthermore, erythrocyte
      copper levels were determined to identify a potential target and Zn levels were
      analyzed to determine a possible change. For the evaluation of hematotoxicity,
      both blood and urine samples were collected for hematological and biochemical
      analyses; moreover, Fe determination was performed. Blood copper and zinc levels,
      red blood cell copper levels as well as copper, zinc, and iron amounts excreted
      into urine were analyzed by ICP-MS. The blood concentration-time profile of
      copper derived from casiopeina III-Ea was fitted to a two-compartment model with
      a zero-order input. Cumulative amounts of Cu, Zn, and Fe excreted into rat urine
      after administration of casiopeina III-Ea were different with respect to control.
      Hematological and biochemical data indicated a hemolytic toxicity.
      Pharmacokinetic analysis of total copper derived from casiopeina III-Ea provided
      a general knowledge about distribution and elimination process of this compound.
      Additionally, the systemic exposure of the copper derived from casiopeina III-Ea
      accounts for the hematotoxicity of this complex at test dose.

PMID- 22958075
TI  - Pathophysiology of primary spinal syringomyelia.
AB  - OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal
      lesion is incompletely understood. The authors hypothesized that in primary
      spinal syringomyelia, a subarachnoid block effectively shortens the length of the
      spinal subarachnoid space (SAS), reducing compliance and the ability of the
      spinal theca to dampen the subarachnoid CSF pressure waves produced by brain
      expansion during cardiac systole. This creates exaggerated spinal subarachnoid
      pressure waves during every heartbeat that act on the spinal cord above the block
      to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed,
      enlarged subarachnoid pressure waves compress the external surface of the spinal
      cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To
      elucidate the pathophysiology, the authors prospectively studied 36 adult
      patients with spinal lesions obstructing the spinal SAS. Testing before surgery
      included clinical examination; evaluation of anatomy on T1-weighted MRI;
      measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest,
      during Valsalva maneuver, during jugular compression, and after removal of CSF
      (CSF compliance measurement); and evaluation with CT myelography. During surgery,
      pressure measurements from the SAS above the level of the lesion and the lumbar
      intrathecal space below the lesion were obtained, and cardiac-gated
      ultrasonography was performed. One week after surgery, CT myelography was
      repeated. Three months after surgery, clinical examination, T1-weighted MRI, and
      CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination
      and MRI studies were repeated annually thereafter. Findings in patients were
      compared with those obtained in a group of 18 healthy individuals who had already
      undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid
      pressure testing. RESULTS: In syringomyelia patients compared with healthy
      volunteers, cervical subarachnoid pulse pressure was increased (2.7 +/- 1.2 vs
      1.6 +/- 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal
      sac below the block was reduced, and spinal CSF compliance was decreased.
      Intraoperative ultrasonography confirmed that pulse pressure waves compressed the
      outer surface of the spinal cord superior to regions of obstruction of the
      subarachnoid space. CONCLUSIONS: These findings are consistent with the theory
      that a spinal subarachnoid block increases spinal subarachnoid pulse pressure
      above the block, producing a pressure differential across the obstructed segment
      of the SAS, which results in syrinx formation and progression. These findings are
      similar to the results of the authors' previous studies that examined the
      pathophysiology of syringomyelia associated with obstruction of the SAS at the
      foramen magnum in the Chiari Type I malformation and indicate that a common
      mechanism, rather than different, separate mechanisms, underlies syrinx formation
      in these two entities. Clinical trial registration no.: NCT00011245.

PMID- 22958077
TI  - Experimental infection of wild-caught European rabbits (Oryctolagus cuniculus)
      with Sarcoptes scabiei from a naturally infected wild rabbit.
AB  - Scabies was recently reported for the first time in the European wild rabbit,
      Oryctolagus cuniculus (Lagomorpha: Leporidae). We experimentally exposed 10
      seronegative wild-caught rabbits to skin from a mangy wild rabbit. Serological,
      physiological, parasitological and histopathological changes were recorded. Three
      rabbits developed antibodies at 2-5 weeks post-infection (w.p.i.), two of which
      then developed lesions at 7 w.p.i. One of these had a small area of alopecia on
      the hind limb that healed naturally within 1 week; the other developed more
      extensive lesions restricted to the hind limbs (as typically observed in wild
      rabbits) that lasted until the rabbit died (12.5 w.p.i.). The third rabbit died
      of trauma 5 w.p.i. before developing any lesions. Antibodies in the healed rabbit
      disappeared from serum at 8 w.p.i., whereas antibody levels in the sick rabbit
      increased until its death. Disseminated intravascular coagulation and hepatic
      necrosis, probably arising from a concomitant infection with rabbit haemorrhagic
      disease virus, were the likely final cause of death in this rabbit. The mangy
      rabbit that served as a donor died of a multifocal fibrinosuppurative pneumonia
      that may have been secondary to the skin bacterial pyoderma.

PMID- 22958078
TI  - Tadalafil once daily for lower urinary tract symptoms suggestive of benign
      prostatic hyperplasia: a randomized placebo- and tamsulosin-controlled 12-week
      study in Asian men.
AB  - OBJECTIVES: To examine the efficacy and safety of tadalafil in Asian men with
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS:
      Asian men with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia were randomized to once-daily placebo (n=154), tadalafil 2.5 mg
      (n=151), tadalafil 5.0 mg (n=155) or tamsulosin 0.2 mg (active control, n=152)
      for 12 weeks. RESULTS: Total International Prostate Symptom Score least-squares
      mean changes from baseline to end-point significantly improved with tadalafil 2.5
      mg (-4.8, P=0.003) and 5 mg (-4.7, P=0.004) versus placebo (-3.0). Significant
      improvement in the International Prostate Symptom Score versus placebo was
      observed earlier (week 2) for tadalafil 5.0 mg than for tadalafil 2.5 mg (week
      8). Significant improvements (P<0.05) in both tadalafil groups versus placebo
      were observed for the International Prostate Symptom Score voiding subscore,
      International Prostate Symptom Score Quality of Life, and for Patient and
      Clinician Global Impressions of Improvement. Significant improvements versus
      placebo were observed in the International Prostate Symptom Score storage
      subscore for tadalafil 5.0 mg (-1.7, P=0.021), but not tadalafil 2.5 mg (-1.5,
      P=0.072). No significant improvements in benign prostatic hyperplasia Impact
      Index or improvements in peak urinary flow rates were observed with tadalafil 2.5
      mg or 5.0 mg versus placebo. Tamsulosin treatment resulted in significant
      improvements versus placebo across all efficacy parameters, except for peak
      urinary flow rates. Safety results were consistent with the known tadalafil and
      tamsulosin safety profiles. CONCLUSIONS: Tadalafil once daily represents an
      effective and well tolerated medical treatment for Asian men presenting with
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

PMID- 22958079
TI  - Directed seed dispersal towards areas with low conspecific tree density by a
      scatter-hoarding rodent.
AB  - Scatter-hoarding animals spread out cached seeds to reduce density-dependent
      theft of their food reserves. This behaviour could lead to directed dispersal
      into areas with lower densities of conspecific trees, where seed and seedling
      survival are higher, and could profoundly affect the spatial structure of plant
      communities. We tested this hypothesis with Central American agoutis and
      Astrocaryum standleyanum palm seeds on Barro Colorado Island, Panama. We radio
      tracked seeds as they were cached and re-cached by agoutis, calculated the
      density of adult Astrocaryum trees surrounding each cache, and tested whether the
      observed number of trees around seed caches declined more than expected under
      random dispersal. Seedling establishment success was negatively dependent on seed
      density, and agoutis carried seeds towards locations with lower conspecific tree
      densities, thus facilitating the escape of seeds from natural enemies. This
      behaviour may be a widespread mechanism leading to highly effective seed
      dispersal by scatter-hoarding animals.

PMID- 22958080
TI  - Effect of drying of jujubes ( Ziziphus jujuba Mill.) on the contents of sugars,
      organic acids, alpha-tocopherol, beta-carotene, and phenolic compounds.
AB  - This study investigated the changes in sugars, organic acids, alpha-tocopherol,
      beta-carotene, phenolic profiles, total phenolic content (TPC), and antioxidant
      capacity of jujube fruits after four drying treatments (sun-, oven-, microwave-
      and freeze-drying). Sugar, organic acid, phenolic compounds, alpha-tocopherol,
      and beta-carotene were qualitatived and quantitatived by high-performance liquid
      chromatography. The TPC and antioxidant activity of jujube samples were evaluated
      using the Folin-Ciocalteau method and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) radical scavenging activity, respectively. Freeze-drying resulted
      in jujubes with higher antioxidant activity and was also a good choice for the
      preparation of beta-carotene from jujubes for the food industry. Microwave-dried
      jujubes had a higher content of protocatechuic acid, catechin, and epicatechin
      and maintained the same antioxidant capacity with the freeze-dried jujubes. The
      combination of microwave- and freeze-drying may be an efficient alternative with
      shorter processing time and, consequently, less impact on the nutritional value
      of the jujube.

PMID- 22958081
TI  - Study of MoNbO(y) (y = 2-5) anion and neutral clusters using photoelectron
      spectroscopy and density functional theory calculations: impact of spin
      contamination on single point calculations.
AB  - Results of a study combining anion photoelectron spectroscopy and density
      functional theory calculations on the heteronuclear MoNbO(y)(-) (y = 2-5)
      transition metal suboxide cluster series are reported and analyzed. The
      photoelectron spectra, which exhibit broad electronic bands with partially
      resolved vibrational structure, were compared to spectral simulations generated
      from calculated spectroscopic parameters for all computationally determined
      energetically competitive structures. Although computational results on the less
      oxidized clusters could not be satisfactorily reconciled with experimental
      spectra, possibly because of heavy spin contamination found in a large portion of
      the computational results, the results suggest that (1) neutral cluster electron
      affinity is a strong indicator of whether O-atoms are bound in M-O-M bridge
      positions or M?O terminal positions, (2) MoNbO(y) anions and neutrals have
      structures that can be described as intermediate with respect to the unary
      (homonuclear) Mo(2)O(y) and Nb(2)O(y) clusters, and (3) structures in which O
      atoms preferentially bind to the Nb center are slightly more stable than
      alternative structures. Several challenges associated with the calculations are
      considered, including spin contamination, which appears to cause spurious single
      point calculations used to determine vertical detachment energies.

PMID- 22958082
TI  - beta-Catenin and E-cadherin expression in stage I adult-type granulosa cell
      tumour of the ovary: correlation with tumour morphology and clinical outcome.
AB  - AIMS:   To study E-cadherin and beta-catenin expression in stage I adult-type
      granulosa cell tumours (AGCTs) and correlate the findings with tumour morphology
      and clinical outcome. METHODS AND RESULTS:   The study group comprised 62 FIGO
      stage I AGCTs, including 48 stage IA and 14 stage IC cases. Fifty patients
      (80.6%) had negative clinical follow-up over periods from 3.0 to 19.2 years
      (median 6.4 years), and 12 patients (19.4%) developed metastases at intervals of
      3.6-16.2 years (median 8.6 years). beta-Catenin and E-cadherin were expressed in
      62 (100%) and 53 (85%) primary tumours, respectively, and staining was more
      consistent and intense in areas showing sex cord-like morphology. In contrast,
      diffuse tumour areas often showed weak or moderate staining (beta-catenin) or
      were negative (E-cadherin), and there was reduced expression of both proteins in
      luteinized cells. Reduced beta-catenin expression in primary tumours correlated
      with increased risk of recurrence (P = 0.002) and a shorter time interval to
      recurrence, whereas there was no correlation between E-cadherin staining and the
      risk of metastases. CONCLUSIONS:   Localized variations in adhesion protein
      expression may partly explain the diverse morphological patterns exhibited by
      AGCT, and reduced beta-catenin staining in primary tumours may have value as an
      adverse prognostic factor.

PMID- 22958083
TI  - Bone mineral density in a population of children and adolescents with cerebral
      palsy and mental retardation with or without epilepsy.
AB  - PURPOSE: The present study aimed to assess bone mineral density (BMD) in a
      population of children and adolescents with cerebral palsy and mental retardation
      with or without epilepsy. METHODS: One hundred thirteen patients (63 male and 50
      female) were recruited for evaluation. Patients were divided in three groups: 40
      patients (group 1) were affected by cerebral palsy and mental retardation; 47
      (group 2) by cerebral palsy, mental retardation, and epilepsy; and 26 (group 3)
      by epilepsy. The control group consisted of 63 healthy children and adolescents.
      Patients underwent a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar
      spine (L1-L4), and z-score was calculated for each patient; t-score was
      considered for patients 18 years of age and older. KEY FINDINGS: Abnormal BMD by
      DEXA was found in 17 patients (42.5%) in group 1, in 33 (70.2%) in group 2, and
      in 3 (11.5%) in group 3. In groups 1 and 2, tetraparesis and severe/profound
      mental retardation were related to a significantly abnormal BMD (p = 0.003). The
      multivariate analysis of independent factors on BMD (z-score) revealed a
      significant correlation between BMD (z-score) and age (p = 0.04), body mass index
      (BMI; p = 0.002), severe/profound mental retardation (p = 0.03), and epilepsy (p
      = 0.05). SIGNIFICANCE: A significantly lower BMD z-score value was found in
      patients with cerebral palsy, mental retardation, and epilepsy compared with
      those without epilepsy. The epileptic disorder appears to be an aggravating
      factor on bone health when comorbid with cerebral palsy and mental retardation.

PMID- 22958084
TI  - Paradoxical embolism as a cause of silent brain infarctions in healthy subjects:
      the ICONS study (Identification of the Cause of Silent Cerebral Infarction in
      Healthy Subjects).
AB  - BACKGROUND: In healthy elderly people, silent brain infarctions (SBIs) have been
      recognized as common lesions. In this study, we evaluated the association between
      SBI located outside the perforating artery territory (PAT) and paradoxical
      embolism detected by agitated saline transcranial Doppler (TCD) monitoring in
      healthy subjects. METHODS: This was a prospective observational study undertaken
      by a university health promotion center for healthy subjects and by a university
      stroke center for acute stroke patients. We defined SBI as evidence on fluid
      attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or
      more infarcts, without history of corresponding stroke or transient ischaemic
      attack. We also evaluated in all subjects the neuroimaging indicator of
      microangiopathy leukoaraiosis (LA). This study is registered with
      ClinicalTrials.gov, number NCT01429948. RESULTS: Amongst 1103 consecutive healthy
      adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT,
      suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD
      monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS
      was similar to cryptogenic embolic stroke (62.0%, P = 0.056), but higher than in
      patients with other stroke subtypes (36.2%, P = 0.021). Amongst subjects with
      SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01
      3.14; P = 0.046). CONCLUSION: Our results suggest that paradoxical embolism may
      play an important role in the development of SBI outside the PAT in apparently
      healthy adults.

PMID- 22958085
TI  - Perspective on ophthalmic support in countries of the developing world.
AB  - There are over 300 million people living in the world today who are visually
      impaired and a further 45 million who are blind. The large majority (90%) of
      these people live in developing countries, and up to 75% of blindness are
      avoidable. With cataracts being the major cause of blindness and visual
      impairment, many ophthalmic aid programmes are aimed at alleviating the enormous
      burden caused by this readily treatable disease. Having said that, caution should
      be exercised that short surgical visits to remote rural areas that are not
      coordinated with local national eye care managers should be discouraged because
      they do little for the development of sustainable eye care programmes. With this
      in view, it has become imperative to design blindness prevention and ophthalmic
      support programmes that are workable, comprehensive, economical and sustainable.

PMID- 22958086
TI  - Poly-L-lysine-coated silver nanoparticles as positively charged substrates for
      surface-enhanced Raman scattering.
AB  - Positively charged nanoparticles to be used as substrates for surface-enhanced
      Raman scattering (SERS) were prepared by coating citrate-reduced silver
      nanoparticles with the cationic polymer poly-l-lysine. The average diameter of
      the coated nanoparticles is 75 nm, and their zeta potential is +62.3 +/- 1.7 mV.
      UV-vis spectrophotometry and dynamic light scattering measurements show that no
      aggregation occurs during the coating process. As an example of their
      application, the so-obtained positively charged coated particles were employed to
      detect nanomolar concentrations of the anionic chromophore bilirubin using SERS.
      Because of their opposite charge, bilirubin molecules interact with the coated
      nanoparticles, allowing SERS detection. The SERS intensity increases linearly
      with concentration in a range from 10 to 200 nM, allowing quantitative analysis
      of bilirubin aqueous solutions.

PMID- 22958087
TI  - Pregnant women's use of the internet in relation to their pregnancy in Izmir,
      Turkey.
AB  - This descriptive and cross-sectional study was conducted in order to determine
      the extent of internet use by pregnant women to gain information about their
      pregnancy. The research was conducted in two hospitals in Izmir, Turkey between
      August and October 2009, after written permission had been obtained. The research
      sample consisted of 185 pregnant women in at least the 28th week of pregnancy,
      who accepted to take part in the study. Forty-five percent of the pregnant women
      had used the internet to obtain information at least once during their pregnancy,
      and the most researched topics were fetal development, nutrition in pregnancy and
      the stages of birth. There is a significant difference between the age group,
      educational level, work status and number of pregnancies and the usage of
      internet among pregnant women. The women gave the information on the internet
      7.13 +/- 1.54 out of 10 points for correctness and dependability. Fifty-one
      percent of the pregnant women stated that they shared the information which they
      had obtained on the internet with health professionals. About half of the women
      in the study had used the internet to obtain information on pregnancy, birth and
      the fetus under various headings.

PMID- 22958088
TI  - AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery:
      a report of the American Academy of Dermatology, American College of Mohs
      Surgery, American Society for Dermatologic Surgery Association, and the American
      Society for Mohs Surgery.
AB  - The appropriate use criteria process synthesizes evidence-based medicine,
      clinical practice experience, and expert judgment. The American Academy of
      Dermatology in collaboration with the American College of Mohs Surgery, the
      American Society for Dermatologic Surgery Association, and the American Society
      for Mohs Surgery has developed appropriate use criteria for 270 scenarios for
      which Mohs micrographic surgery (MMS) is frequently considered based on tumor and
      patient characteristics. This document reflects the rating of appropriateness of
      MMS for each of these clinical scenarios by a ratings panel in a process based on
      the appropriateness method developed by the RAND Corp (Santa Monica,
      CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the
      rating process, consensus was reached for all 270 (100%) scenarios by the Ratings
      Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46
      (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were
      deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell
      carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34
      inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were
      deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous
      malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2
      inappropriate. These appropriate use criteria have the potential to impact health
      care delivery, reimbursement policy, and physician decision making on patient
      selection for MMS, and aim to optimize the use of MMS for scenarios in which the
      expected clinical benefit is anticipated to be the greatest. In addition,
      recognition of those scenarios rated as uncertain facilitates an understanding of
      areas that would benefit from further research. Each clinical scenario identified
      in this document is crafted for the average patient and not the exception. Thus,
      the ultimate decision regarding the appropriateness of MMS should be determined
      by the expertise and clinical experience of the physician.

PMID- 22958089
TI  - Troger's base twisted amides: endo functionalization and synthesis of an inverted
      crown ether.
AB  - Taking advantage of the unconventional reactivity of twisted mono- and bis-amides
      of Troger's base (TB), rac-6 and rac-7, respectively, the first synthesis of a 6
      endo-monosubstituted TB analogue, rac-9, and the first rational synthesis of a
      6,12-endo,endo-disubstituted TB analogue, rac-11, have been achieved. The bis-TB
      crown ether, meso-13, was prepared starting from rac-7. Meso-13 constitutes a
      rare example of a crown ether with an inverted methylene bridge-to-bridge bis-TB
      conformation both in solution and in the solid state, resulting in a reluctance
      to act as a receptor for cations.

PMID- 22958090
TI  - Erythema multiforme possibly triggered by rabies vaccine in a 10-year-old boy.
AB  - This report documents a possible rabies vaccine-induced erythema multiforme
      manifestation in a 10-year-old boy. 

PMID- 22958091
TI  - Abstracts of the 5th Special Conference of the International Society for
      Neurochemistry, Synapses and Dendritic Spines in Health and Disease. Buenos
      Aires, Argentina. September 12-15, 2012.

PMID- 22958092
TI  - RHCE*cE734C allele encodes an altered c antigen and a suppressed E antigen not
      detected with standard reagents.
AB  - BACKGROUND: The RH blood group system has many RHCE variant alleles that have
      arisen through gene conversion or nucleotide changes. Two probands, with red
      blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to
      resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests
      were performed by automated and manual procedures. Genomic DNA analysis was
      performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands'
      RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad,
      Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with
      anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with
      the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the
      presence of C/G at Position 676 (E/e polymorphism) and the association of the E
      polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro
      amino acid substitution in the mature RhcE polypeptide. Replacement of leucine
      245 by proline in the eighth transmembrane domain of the RhcE protein may have a
      steric effect on the protein such that most anti-E reagents do not bind and the
      interaction between anti-c and c antigen is also affected. CONCLUSION: We report
      a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT
      allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had
      weakened c expression and typed E- with conventional anti-E reagents. These data,
      once again, highlight the fact that the genotype does not always reflect the
      phenotype.

PMID- 22958094
TI  - Molecular phylogeny and identification of the peach fruit fly, Bactrocera zonata,
      established in Egypt.
AB  - The genetic structure of the Egyptian peach fruit fly (Bactrocera zonata
      (Saunders) (Diptera: Tephritidae)) population was analyzed using total RNA from
      adult females. A portion of mitochondrial cytochrome oxidase I (COI), 369 bp was
      amplified using RT-PCR, and was sequenced and analyzed to clarify the
      phylogenetic relationship of B. zonata established in Egypt. The data suggested
      that the gene shared a similarity in sequence compared to Bactrocera COI gene
      found in GenBank. Molecular phylogenetic analyses were performed based on
      nucleotide sequences in order to examine the position of the Egyptian population
      among many other species of fruit flies. The results indicate that four accession
      numbers of B. zonata (three from New Zealand and one from India) are closely
      related, while the Egyptian B. zonata are close to the 71 accession numbers of
      Bactrocera include one B. zonata from New Zealand. These two B. zonata from Egypt
      and New Zealand showed a close relationship in neighbor-joining analysis using
      the seven accession numbers of B. zonata. In addition, a theoretical restriction
      map of the homology portion of the COI gene was constructed using 212 restriction
      enzymes obtained from the restriction enzyme database to identify the Egyptian
      and New Zealand B. zonata.

PMID- 22958093
TI  - Vasodilator and antihypertensive effects of a novel N-acylhydrazone derivative
      mediated by the inhibition of L-type Ca2+ channels.
AB  - New bioactive N-acylhydrazone derivatives synthesized from safrole previously
      have been found to promote intense vasodilation and antihypertensive activity. In
      this study, we describe the synthesis and the cardiovascular effects of the new N
      acylhydrazone derivative (E)-N-methyl-N'-(thiophen-3
      ylmethylene)benzo[d][1,3]dioxole-5-carbohydrazide (LASSBio-1289). Thoracic aorta
      and left papillary muscles from Wistar-Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHR) were prepared for isometric tension recording. LASSBio
      1289 promoted relaxation of endothelium-intact and denuded aortic rings with
      respective pIC50 (-log IC50) values of 5.07 +/- 0.09 and 4.26 +/- 0.09 (P <
      0.001) for WKY rats and 5.43 +/- 0.05 and 5.58 +/- 0.07 (P > 0.05) for SHR. The
      vasodilator activity of LASSBio-1289 was increased in the KCl-contracted aorta.
      LASSBio-1289 attenuated the contracture elicited by Ca(2+) in depolarized aorta
      from both WKY rats and SHR. In endothelium-intact aorta from WKY rats, LASSBio
      1289-induced relaxation was unchanged after incubation with propranolol, ZM
      241385, atropine, diphenhydramine, and HOE140, but was significantly reduced by L
      NAME and ODQ. LASSBio-1289 decreased papillary muscles contractility only at
      concentrations above 200 MUm. Acute intravenous injection of LASSBio-1289 (3
      mg/kg) produced a significant hypotensive response in SHR but not in WKY rats,
      suggesting its antihypertensive profile. The antihypertensive effect was also
      observed in SHR during 14 days of intraperitoneal and oral administration. In
      conclusion, our data demonstrated that LASSBio-1289 induces both endothelium
      independent vasorelaxation involving the inhibition of Ca(2+) influx through L
      type Ca(2+) channels in aorta from WKY rats and SHR, and endothelium-dependent
      relaxation mediated by the NO/cyclic GMP pathway in WKY rats.

PMID- 22958095
TI  - World Sepsis Day: September 13, 2012.

PMID- 22958096
TI  - Pulmonary aspergillosis in chronic leflunomide treatment.

PMID- 22958098
TI  - Selective gas and vapor sorption and magnetic sensing by an isoreticular mixed
      metal-organic framework.
AB  - A novel isoreticular oxamato-based manganese(II)-copper(II) open metal-organic
      framework H(2)O@iso1 featuring a pillared square/octagonal layer structure with
      alternating open and closed octagonal pores has been rationally prepared. The
      open-framework topology is responsible for a large selectivity in the separation
      of small gas (CO(2) over CH(4)) and vapor molecules (CH(3)OH over CH(3)CN and
      CH(3)CH(2)OH). H(2)O@iso1 displays a long-range three-dimensional ferromagnetic
      ordering with a drastic variation of the critical temperature as a function of
      the guest molecule [T(C) < 2.0 K (CO(2)@iso1 and CH(4)@iso1) and T(C) = 6.5
      (CH(3)OH@iso1) and 21.0 K (H(2)O@iso1)].

PMID- 22958097
TI  - Reactive nitrogen oxide species-induced post-translational modifications in human
      hemoglobin and the association with cigarette smoking.
AB  - Nitric oxide (NO) is essential for normal physiology, but excessive production of
      NO during inflammatory processes can damage the neighboring tissues. Reactive
      nitrogen oxide species (RNOx), including peroxynitrite (ONOO(-)), are powerful
      nitrating agents. Biological protein nitration is involved in several disease
      states, including inflammatory diseases, and it is evident by detection of 3
      nitrotyrosine (3NT) in inflamed tissues. In this study, we identified
      peroxynitrite-induced post-translational modifications (PTMs) in human hemoglobin
      by accurate mass measurement as well as by the MS(2) and MS(3) spectra. Nitration
      on Tyr-24, Tyr-42 (alpha-globin), and Tyr-130 (beta-globin) as well as
      nitrosation on Tyr-24 (alpha-globin) were identified. Also characterized were
      oxidation of all three methionine residues, alpha-Met-32, alpha-Met-76, and beta
      Met-55 to the sulfoxide, as well as cysteine oxidation determined as sulfinic
      acid on alpha-Cys-104 and sulfonic acid on alpha-Cys-104, beta-Cys-93, and beta
      Cys-112. These modifications are detected in hemoglobin freshly isolated from
      human blood and the extents of modifications were semiquantified relative to the
      reference peptides by nanoflow liquid chromatography-nanospray ionization tandem
      mass spectrometry (nanoLC-NSI/MS/MS) under the selected reaction monitoring (SRM)
      mode. The results showed a statistically significant positive correlation between
      cigarette smoking and the extents of tyrosine nitration at alpha-Tyr-24 and at
      alpha-Tyr-42. To our knowledge, this is the first report on identification and
      quantification of multiple PTMs in hemoglobin from human blood and association of
      a specific 3NT-containing peptide with cigarette smoking. This highly sensitive
      and specific assay only requires hemoglobin isolated from one drop (~10 MUL) of
      blood. Thus, measurement of these PTMs in hemoglobin might be feasible for
      assessing nitrative stress in vivo.

PMID- 22958100
TI  - Fungal importance extends beyond litter decomposition in experimental early
      successional streams.
AB  - Fungi are important decomposers of leaf litter in streams and may have knock-on
      effects on other microbes and carbon cycling. To elucidate such potential
      effects, we designed an experiment in outdoor experimental channels simulating
      sand-bottom streams in an early-successional state. We hypothesized that the
      presence of fungi would enhance overall microbial activity, accompanied by shifts
      in the microbial communities associated not only with leaf litter but also with
      sediments. Fifteen experimental channels received sterile sandy sediment, minimal
      amounts of leaf litter, and one of four inocula containing either (i) fungi and
      bacteria, or (ii) bacteria only, or (iii) no microorganisms, or (iv) killed
      microorganisms. Subsequently, we let water from an early-successional catchment
      circulate through the channels for 5 weeks. Whole-stream metabolism and microbial
      respiration associated with leaf litter were higher in the channels inoculated
      with fungi, reflecting higher fungal activity on leaves. Bacterial communities on
      leaves were also significantly affected. Similarly, increases in net primary
      production, sediment microbial respiration and chlorophyll a content on the
      sediment surface were greatest in the channels receiving a fungal inoculum. These
      results point to a major role of fungal communities in stream ecosystems beyond
      the well-established direct involvement in leaf litter decomposition.

PMID- 22958099
TI  - Comparison of small molecule inhibitors of the bacterial cell division protein
      FtsZ and identification of a reliable cross-species inhibitor.
AB  - FtsZ is a guanosine triphosphatase (GTPase) that mediates cytokinesis in
      bacteria. FtsZ is homologous in structure to eukaryotic tubulin and polymerizes
      in a similar head-to-tail fashion. The study of tubulin's function in eukaryotic
      cells has benefited greatly from specific and potent small molecule inhibitors,
      including colchicine and taxol. Although many small molecule inhibitors of FtsZ
      have been reported, none has emerged as a generally useful probe for modulating
      bacterial cell division. With the goal of establishing a useful and reliable
      small molecule inhibitor of FtsZ, a broad biochemical cross-comparison of
      reported FtsZ inhibitors was undertaken. Several of these molecules, including
      phenolic natural products, are unselective inhibitors that seem to derive their
      activity from the formation of microscopic colloids or aggregates. Other
      compounds, including the natural product viriditoxin and the drug development
      candidate PC190723, exhibit no inhibition of GTPase activity using protocols in
      this work or under published conditions. Of the compounds studied, only zantrin
      Z3 exhibits good levels of inhibition, maintains activity under conditions that
      disrupt small molecule aggregates, and provides a platform for exploration of
      structure-activity relationships (SAR). Preliminary SAR studies have identified
      slight modifications to the two side chains of this structure that modulate the
      inhibitory activity of zantrin Z3. Collectively, these studies will help focus
      future investigations toward the establishment of probes for FtsZ that fill the
      roles of colchicine and taxol in studies of tubulin.

PMID- 22958101
TI  - Selection, characterization, and biosensing application of high affinity congener
      specific microcystin-targeting aptamers.
AB  - The efficiency of current microcystin detection methods has been hampered by the
      low detection limits required in drinking water and that routine detection is
      restricted to a few of the congeners with high degree of undesired cross
      reactivity. Here, we report the development of novel microcystin-targeting
      molecules and their application in microcystin detection. We have selected DNA
      aptamers from a diverse random library that exhibit high affinity and specificity
      to microcystin-LR, -YR, and -LA. We obtained aptamers that bind to all chosen
      congeners with high affinity with K(D) ranging from 28 to 60 nM. More
      importantly, we also obtained aptamers that are selective among the different
      congeners, with selectivity from 3-folds difference in binding affinity to total
      discrimination (K(D) of 50 nM versus nonspecific binding). Electrochemical
      aptasensors constructed with the selected aptamers were able to achieve sensitive
      and congener-specific microcystin detection with detection limit as low as 10 pM.

PMID- 22958102
TI  - The role of temperature in cloud droplet activation.
AB  - Aerosols are prevalent in the atmosphere where they can serve as cloud
      condensation nuclei (CCN). Here we report on new CCN measurements to characterize
      the temperature dependence of CCN activity for single component organic aerosol
      and secondary organic aerosol from the reaction of alpha-pinene and O(3)
      generated in the laboratory. For compounds with a weak dependence of water
      activity on temperature, the critical supersaturation of the particles can be
      well-modeled using temperature-dependent surface tension and Kohler theory. We
      also demonstrate that Kohler theory is valid for sparingly soluble compounds and
      can quantitatively explain the temperature-dependent activation properties of
      adipic acid aerosol over a broad range of temperatures. Accounting for
      temperature-dependent surface tension strongly affects CCN activity, and we
      anticipate that including this effect in global and regional model simulations
      may significantly change the estimated aerosol indirect forcing.

PMID- 22958103
TI  - Efficient production and characterization of the sweet-tasting brazzein secreted
      by the yeast Pichia pastoris.
AB  - Brazzein is a small, heat-, and pH-stable sweet protein present in the fruits of
      the West African plant  Pentadiplandra brazzeana  Baillon. It exists in two forms
      differing in sweetness intensity. The major form, called pyrE-bra, contains a
      pyroglutamic acid at its N-terminus, while the minor form, called des-pyrE-bra,
      lacks this residue. Here we describe the heterologous expression in the
      methylotrophic yeast  Pichia pastoris  of two natural forms of brazzein, pyrE-bra
      and des-pyrE-bra, and an additional form, called Q1-bra, which is not naturally
      occurring in the fruit. Q1-bra differs from pyrE-bra in having a glutamine
      residue instead of pyrE at its N-terminus. Over an expression period of 6 days,
      we obtained approximately 90, 30, and 90 mg/L of purified recombinant pyrE-bra,
      Q1-bra, and des-pyrE-bra brazzein forms, respectively. Recombinant proteins were
      purified and submitted to mass spectrometry and (1)H NMR spectroscopy. The data
      indicate that the recombinant brazzein forms were properly folded. Moreover, they
      activated the human sweet receptor in vitro and evoked sweetness in vivo with
      properties similar to those of the two natural brazzein forms.

PMID- 22958104
TI  - The effect of urea and ammonia treatments on the survival of Salmonella spp. and
      Yersinia enterocolitica in pig slurry.
AB  - AIMS: The objective of this study was to investigate the survival of Salmonella
      and Yersinia enterocolitica strains in pig slurry and evaluate urea and ammonia
      as disinfection strategies. METHODS AND RESULTS: Salmonella Anatum, Salmonella
      Derby, Salmonella Typhimurium DT19 and Y. enterocolitica bioserotypes 4, O:3, 2,
      O:5,27 and 1A, O:6,30 were selectively marked by insertion of the plasmid, pGLO
      encoding for green fluorescent protein and for ampicillin resistance. Strain
      cocktails were inoculated into fresh pig slurry (control), slurry treated with
      urea [final concentration 2% w/w, (0.33 mol l(-1) )] and slurry treated with
      ammonia [final concentration 0.5% w/w, (0.3 mol l(-1) )] and stored at 4, 14 and
      25 degrees C. Bacterial counts were determined at regular intervals on xylose
      lysine deoxycholate agar (XLD), and XLD supplemented with ampicillin (0.1 mg ml(
      1) ) and arabinose (0.6 mg ml(-1) ) for Salmonella and cefsulodin-irgasan
      novobiocin agar (CIN) and CIN supplemented with ampicillin and arabinose for Y.
      enterocolitica. The pH of the control-, urea- and ammonia-treated samples ranged
      from 7.1 to 7.7, 8.8 to 8.9 and 8.0 to 8.3, respectively. Salmonella D(4) values
      ranged from 2.71 to 21.29 days, D(14) values from 2.72 to 11.62 days and D(25)
      values from 1.76 to 6.85 days. The equivalent D values ranges for the Y.
      enterocolitica strains were 3.7-19.23, 1.8-16.67 and 1.63-7.09 days,
      respectively. Treatment significantly (P < 0.01) affected D values with control >
      ammonia > urea, as did incubation temperature; 4 > 14 > 25 degrees C.
      CONCLUSIONS: Urea and to a lesser extent ammonia may be used to disinfect
      Salmonella- and/or Y. enterocolitica-contaminated pig slurry, decreasing the
      storage time required while increasing its fertilizer value. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study presents data supporting the treatment of pig
      slurry to kill important zoonotic agents, thereby reducing environmental
      contamination, cross-infection of other animals and decreasing zoonotic disease
      in the food chain.

PMID- 22958105
TI  - Effectiveness of FDA's new over-the-counter acetaminophen warning label in
      improving consumer risk perception of liver damage.
AB  - WHAT IS KNOWN AND OBJECTIVES: The Food and Drug Administration (FDA) issued new
      organ-specific warning label requirements for over-the-counter (OTC) analgesic
      products in order to make consumers aware of the risk of liver damage when using
      acetaminophen. However, awareness of a health risk alone cannot ensure consumers'
      engagement in safe and preventive behaviour. In this study, we attempted to: (i)
      measure consumer risk perception of liver damage due to the OTC acetaminophen
      products and (ii) analyse the effectiveness of the new organ-specific warning
      label in improving consumer risk perception of liver damage and intention to
      perform protective behaviours while using OTC acetaminophen products. METHODS:
      This within-subject experimental study used a convenience sample of English
      speaking adults visiting OTC segments of selected pharmacy stores in Houston.
      Participants were randomly exposed to the old and new warning labels and their
      respective risk perception (measured on a visual analogue scale, 0%, no risk, to
      100%, extreme risk) and behavioural intention (measured on a 7-point Likert
      scale) were recorded using a validated, self-administered questionnaire.
      Descriptive statistics and non-parametric Wilcoxon signed-rank tests were
      performed using sas statistical software (v 9.2) at a priori significance level
      of 0.05. RESULTS AND DISCUSSION: Majority of participants (74.4%) were not aware
      of the new warnings; however, majority (67.8%) had prior knowledge of the risk.
      The mean risk perception score for the new warning label was found to be
      significantly higher (72.2% vs. 65.9%, P < 0.0001) than the old warning label.
      Similarly, the average intention score for the new warning label was
      significantly higher (5.06 vs. 4.86, P < 0.0001) than the old warning label. WHAT
      IS NEW AND CONCLUSION: The new warning label mandated by FDA is effective in
      improving consumer risk perception of potential liver damage and may encourage
      protective behaviour. However, future studies are essential to assess the impact
      of the new label on actual changes in consumer behaviour and subsequent reduction
      in acetaminophen-related morbidity and mortality.

PMID- 22958106
TI  - Editorial Comment to patent processus vaginalis in adults who underwent robot
      assisted laparoscopic radical prostatectomy: predictive signs of postoperative
      inguinal hernia in the internal inguinal floor.

PMID- 22958108
TI  - A web-based intensive care clinical decision support system: from design to
      evaluation.
AB  - The aim of this study is to develop and evaluate a web-based clinical decision
      support system (CDSS) containing clinical guidelines and protocols that will
      support intensive care unit (ICU) providers in making decisions more effectively
      and quickly. First, a survey was carried out with 38 physicians in order to
      determine their preferences, needs and concerns regarding decision support tools.
      After the survey, guidelines were prepared by a group of specialists in ICU, and
      a medical informatician converted the guidelines into algorithm forms. Ten CDSS
      were developed using the algorithms, and placed onto the Intensive Care Decision
      Support Website (ICDSW). In order to evaluation of the website, 15 physicians
      were asked to answer 10 questions in 10 different scenarios first using a paper
      based approach, then with ICDSW. When the answers were analyzed, it was found
      that the answers given by using ICDSW were significantly better than the paper
      based approach (p <  0.001). However, there was no significant difference in
      terms of the time needed to answer the questions (p =  0.138). The usability
      score of the website was 85.6 +/-  8.89. The study demonstrated the successful
      implementation of an ICDSW within intensive care units.

PMID- 22958107
TI  - Implementing Dialectical Behaviour Therapy: programme survival in routine
      healthcare settings.
AB  - BACKGROUND: The National Institute of Health and Clinical Excellence recommends
      considering Dialectical Behaviour Therapy (DBT), an efficacious treatment for
      borderline personality disorder, especially when reduction in self-harm is a
      clinical priority [ NCCMH (2009) . Borderline Personality Disorder: Treatment and
      Management. Leicester: The British Psychological Society and the Royal College of
      Psychiatrists]. Treatment teams began using DBT in the UK in 1994. Concerns have
      been raised, however, about the sustainability of DBT programmes in routine
      clinical practice [Pitman, A., & Tyrer, P. (2008). Implementing clinical
      guidelines for self-harm - highlighting key issues arising from the NICE
      guideline for self-harm. Psychology and Psychotherapy: Theory, Research and
      Practice, 81, 377-397]. AIMS: This study sought to establish the sustainability
      of UK DBT programmes and to explore factors that impacted on effective
      implementation. METHOD: All teams trained in DBT in the UK between 1994 and 2007
      were contacted. Each team was categorised as either active or inactive. The date
      of programme cessation was established. Team leaders of active, and as far as
      possible inactive, programmes were interviewed about aspects of implementation.
      RESULTS: The survival curve demonstrated that DBT programmes ran an increased
      risk of failure in the second and fifth years after training. Absence of
      organisational support and staff turnover were the most commonly reported
      implementation challenges. CONCLUSIONS: Sustainable implementation of DBT, as
      with other evidence-based interventions, requires organisational support that
      incorporates a strategy for further staff training and development.

PMID- 22958109
TI  - Longitudinal effect of topical antiglaucoma medications on central corneal
      thickness.
AB  - BACKGROUND: To determine the change in central corneal thickness over time and
      whether the use of long-term topical antiglaucoma medications influences central
      corneal thickness. DESIGN: Case control study with retrospective and prospective
      data collection. PARTICIPANTS: One hundred eighty-seven eyes of 187 glaucoma
      patients (mean follow up 6.92 +/- 1.67 years) being treated with topical
      antiglaucoma medications (at least 3 years) with no history of surgery or laser
      were included and compared with 100 eyes of 100 age-matched, untreated control
      subjects (mean follow up 6.58 +/- 1.93 years) who were glaucoma suspects with
      normal intraocular pressure not on any treatment. METHODS: Demographic data,
      central corneal thickness and intraocular pressure were collected at initial
      glaucoma diagnosis and at most recent visit, and findings were compared between
      two groups. MAIN OUTCOME MEASURES: Mean change in central corneal thickness in
      microns (MUm). RESULTS: Central corneal thickness fell significantly (P < 0.0001)
      in treated eyes but not in control eyes (P = 0.18); mean central corneal
      thickness reduction was 12.29 +/- 13.65 MUm in treated eyes and 1.17 +/- 8.75 MUm
      in controls. Among treated eyes, central corneal thickness reduction was
      significant (P < 0.0001) in those treated with either prostaglandins or a
      combination of prostaglandin and beta-blockers, while no significant reduction
      occurred in eyes treated with only beta-blockers (P = 0.15) when compared with
      control eyes. CONCLUSIONS: Prostaglandins appear to be associated with a small
      but significant central corneal thickness reduction over time. Serial central
      corneal thickness measurements might be helpful in glaucoma patients,
      particularly those on prostaglandins.

PMID- 22958110
TI  - Corannulene subunit acts as a diene in a cycloaddition reaction: synthesis of
      C80H32 corannulyne tetramer.
AB  - Distortion of six-membered rings in corannulene subunits of corannulyne (1,2
      didehydrocorannulene) cyclotrimer activates the system for a cycloaddition
      reaction with another corannulyne unit. This unprecedented cycloaddition in which
      a corannulene fragment acts as a diene produces the largest oligomer of
      corannulyne reported to date. X-ray crystallography reveals the highly nonplanar
      structure of the tetramer which exhibits conformational and optical absorption
      properties very different from those of the cyclotrimer.

PMID- 22958111
TI  - Is the CAT questionnaire sensitive to changes in health status in patients with
      severe COPD exacerbations?
AB  - The COPD Assessment Test (CAT) was validated in English showing good psychometric
      properties. The objective of this study is to assess the capacity of the CAT to
      detect changes in health status in patients experiencing COPD exacerbations
      (ECOPD) and to further explore the validity of the Spanish version. An
      observational study was conducted in 49 Spanish centres. Patients hospitalised
      because of ECOPD (n = 224) completed the CAT, the St. George's Respiratory
      Questionnaire-adapted for COPD (SGRQ-C) and the London Chest Activities of Daily
      Living (LCADL) questionnaire during the first 48 hours of admission and 4 +/- 1
      weeks after discharge. Stable patients (n = 153) also completed these at
      recruitment and 4 +/- 1 weeks later. Over 90% of patients were male. The CAT
      discriminated between stable and ECOPD patients (15.8 vs 22.4, p < 0.01), as well
      as between patients with different levels of airflow limitation and dyspnea (MRC
      scale). The CAT proved sensitive to change; change in mean score was 8.9 points
      (effect size (ES), 0.90) in ECOPD patients reporting their health state as "much
      better" after discharge, 4.8 points in those reporting "quite a lot better" (ES =
      0.63), and 4.6 points in those reporting "slightly better" (ES = 0.59).
      Cronbach's alpha and Intraclass Correlation Coefficient were 0.86 and 0.83,
      respectively. It correlated with both the SGRQ (r = 0.82; p < 0.01) and the LCADL
      (r = 0.63; p < 0.01). Change in CAT correlated well with Delta SGRQ (r = 0.63; p
      < 0.01). The CAT showed to be sensitive to the change in health status associated
      with ECOPD. We also provide evidence of the validity of the Spanish version.

PMID- 22958112
TI  - Geographic variation of epilepsy for older Americans: how close to the geographic
      variation of stroke?
AB  - PURPOSE: Given the strong association of stroke and epilepsy in older persons,
      and the existence of a Stroke Belt in the United States, we hypothesized that
      geographic variation in epilepsy prevalence would follow geographic patterns
      similar to stroke. METHODS: We used a 2005 5% random sample of Medicare
      beneficiaries 65 and older in 48 U.S. contiguous states. Epilepsy was identified
      from claims for physician visits, hospitalizations, and outpatient procedures.
      Prevalence was obtained by state and county. Logistic regressions determined the
      independent association of the likelihood of epilepsy (prevalent or new case) and
      residence in Stroke Belt states, controlling for residence in highest epilepsy
      prevalence states, demographics (race, age, gender), comorbid conditions,
      cerebrovascular disease, dementia, and county characteristics. KEY FINDINGS: Of
      1,212,015 beneficiaries, 11.9 per 1,000 had prevalent and 2.9 new cases of
      epilepsy. Nine of 11 Stroke Belt states were among the 20 states with the highest
      epilepsy prevalence. Counties in the 10 highest epilepsy prevalence states were
      more likely to be large urban counties with a higher number of neurologists or
      neurosurgeons per capita. The higher likelihood of prevalent epilepsy cases
      associated with Stroke Belt residence was explained by beneficiaries' race; that
      associated with residence in high epilepsy prevalence states was not. The
      likelihood of new epilepsy cases was negatively associated with Stroke Belt
      residence when controlling for covariates. SIGNIFICANCE: The geographic variation
      in epilepsy prevalence is not explained by variations in known risk factors.
      Further research should investigate why eastern U.S. states have higher frequency
      of epilepsy.

PMID- 22958113
TI  - Facial lichen striatus in children: retracing the lines of Blaschko.
AB  - We report seven patients with facial lichen striatus along the lines of Blaschko
      who presented to our pediatric dermatology unit between 2003 and 2009. The mean
      age of diagnosis was 4.6 years (range 2.5-9 years). Three of the cases were
      associated with atopic dermatitis, and one case presented with vitiligo. In the
      six patients for whom we have follow-up, all lesions resolved without pigmentary
      changes in an average of 11 months. This case series describes the distribution,
      presentation, and natural history of lichen striatus along facial lines of
      Blaschko. From our experience, clinical diagnosis and monitoring without biopsy
      is a reasonable approach to the management of uncomplicated lichen striatus,
      particularly when the face is involved.

PMID- 22958114
TI  - Cerebral hypoperfusion and white matter disease in healthy elderly and patients
      with Alzheimer's disease.

PMID- 22958115
TI  - Perceptions of expertise in cutaneous surgery and cosmetic procedures: what
      primary care physicians think.
AB  - BACKGROUND: Primary care physician (PCP) perceptions regarding expertise in
      cutaneous surgery and cosmetic procedures are unknown. METHODS: An internet-based
      survey was administered to physicians in primary care medicine residency programs
      in the United States. Respondents were asked to select the specialist most
      qualified to perform different cutaneous cosmetic and surgical procedures.
      RESULTS: Five hundred sixty-one PCPs undertook the survey. Dermatologists were
      identified as the most qualified specialist to evaluate and biopsy worrisome
      lesions on the face (95%), perform skin cancer surgery (56%), inject botulinum
      toxin (61%), inject fillers (55%), and perform laser procedures (75%). Seventy
      percent of respondents correctly defined Mohs micrographic surgery (MMS), and 60%
      of respondents selected a fellowship-trained dermatologist as the best physician
      to perform MMS. U.S. medical school graduates were more likely than foreign
      medical school graduates to select a Mohs fellowship-trained dermatologist as the
      most qualified physician to perform MMS (adjusted odds ratio (AOR) = 1.52, 95%
      confidence interval (CI) = 1.05-2.21). PCPs without exposure to dermatology in
      medical school were about half as likely those with exposure to correctly define
      MMS (AOR = 0.51, 95% CI = 0.30-0.89). CONCLUSIONS: Dermatologists are recognized
      as the most qualified specialist to perform a variety of cutaneous cosmetic and
      surgical procedures, including skin cancer surgery, botulinum toxin injections,
      filler injections, and laser procedures. Mohs fellowship-trained dermatologists
      were viewed as more qualified to perform MMS than other dermatologists, plastic
      surgeons, otolaryngologists, or ophthalmologists.

PMID- 22958116
TI  - Large-scale bone mineral histomorphometry-report of a simplified technique.
AB  - AIMS: The aim of this study was the development of a simplified technique for
      bone mineral histomorphology on large undecalcified bone samples. Established
      techniques, such as undecalcified bone thin sectioning, ultrathin grinding,
      surface-stained block grinding and micro-computerized tomography (CT), are
      expensive, time-consuming and put very high demands on equipment, safety
      standards, personnel and laboratory facilities. METHODS AND RESULTS: The method
      is based on the surface-stained block-grinding principle; however, its novelty
      lies in the selection of user-friendly, safe and low-cost materials, equipment
      and digitization techniques. We describe in detail the relevant steps, as well as
      many practical tips for their successful implementation: accurate bone cutting in
      thin sections with a customized arrangement on a commercial bandsaw, defatting
      with sodium hypochlorite, embedding in epoxy resin blocks at room temperature,
      silicon carbide paper grinding, von Kossa staining, flatbed scanner digitization
      and image processing. CONCLUSION: We believe that the proposed methodology could
      contribute to the expansion of the study of bone tissue, as it enables the rapid
      examination of bone specimens on a large scale with minimal laboratory
      requirements and consumables costs.

PMID- 22958117
TI  - Body fat distribution and risk factors for fibrosis in patients with alcoholic
      liver disease.
AB  - BACKGROUND: Only a small proportion of alcoholic patients develop advanced liver
      disease, suggesting that factors other than alcohol intake may influence
      alcoholic liver disease (ALD) progression. We have shown that body mass index
      (BMI) is an independent risk factor for fibrosis in alcohol-induced liver disease
      and that adipose tissue inflammation is correlated with liver lesions in
      alcoholic patients. The aim of this study was to determine whether visceral
      adipose tissue, as assessed by abdominal height measurement, affected individual
      susceptibility to fibrosis in alcoholic patients. METHODS: We included 127
      consecutive alcoholic patients with abnormal liver test findings for whom liver
      histology data were available. Abdominal height was measured with a Holtain-Kahn
      abdominal caliper. We carried out univariate comparisons followed by multivariate
      regression analysis, to investigate the relationship between abdominal height and
      fibrosis score. RESULTS: Abdominal height (p < 0.005), waist circumference (p <
      0.05), fasting blood glucose concentration (p < 0.05), serum triglyceride
      concentration (p < 0.05), serum bilirubin (p < 0.005), and BMI (p = 0.05) were
      higher, whereas high-density lipoprotein (HDL) cholesterol level (p < 0.01) was
      lower in the 72 patients with significant (F2-F4) fibrosis than in the 55
      patients with F0-F1 fibrosis. In multivariate regression analysis, only abdominal
      height (beta = 7.2, p < 0.002) was independently and positively correlated with
      fibrosis score, which was also negatively correlated with HDL cholesterol level
      (beta = -1.04, p < 0.05). CONCLUSIONS: We provide the first demonstration that
      abdominal height may be a predictor of significant fibrosis in patients with ALD.
      Our findings support a role for visceral fat accumulation, independent of BMI and
      of metabolic syndrome criteria, in the onset of alcoholic liver damage.

PMID- 22958118
TI  - Imparting high proton conductivity to a metal-organic framework material by
      controlled acid impregnation.
AB  - The extensive implementation of hydrogen-powered technology today is limited by a
      number of fundamental problems related to materials research. Fuel-cell hydrogen
      conversion technology requires proton-conducting materials with high conductivity
      at intermediate temperatures up to 120  degrees C. The development of such
      materials remains challenging because the proton transport of many promising
      candidates is based on extended microstructures of water molecules, which
      deteriorate at temperatures above the boiling point. Here we show the
      impregnation of the mesoporous metal-organic framework (MOF) MIL-101 by
      nonvolatile acids H(2)SO(4) and H(3)PO(4). Such a simple approach affords solid
      materials with potent proton-conducting properties at moderate temperatures,
      which is critically important for the proper function of on-board automobile fuel
      cells. The proton conductivities of the H(2)SO(4)@MIL-101 and H(3)PO(4)@MIL-101
      at T = 150  degrees C and low humidity outperform those of any other MOF-based
      materials and could be compared with the best proton conductors, such as Nafion.

PMID- 22958119
TI  - Agrobacteria lacking ornithine lipids induce more rapid tumour formation.
AB  - Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread
      among Gram-negative bacteria. Their basic structure consists of a 3-hydroxy fatty
      acyl group attached in amide linkage to the alpha-amino group of ornithine and a
      second fatty acyl group ester-linked to the 3-hydroxy position of the first fatty
      acid. It has been shown that OLs can be hydroxylated within the amide-linked
      fatty acyl moiety, the secondary fatty acyl moiety or within the ornithine
      moiety. These modifications have been related to increased stress tolerance and
      symbiotic proficiency in different organisms such as Rhizobium tropici or
      Burkholderia cenocepacia. Analysing the membrane lipid composition of the plant
      pathogen Agrobacterium tumefaciens we noticed that it forms two different OLs. In
      the present work we studied if OLs play a role in stress tolerance and
      pathogenicity in A. tumefaciens. Mutants deficient in the OLs biosynthesis genes
      olsB or olsE were constructed and characterized. They either completely lack OLs
      (DeltaolsB) or only form the unmodified OL (DeltaolsE). Here we present a
      characterization of both OL mutants under stress conditions and in a plant
      transformation assay using potato tuber discs. Surprisingly, the lack of
      agrobacterial OLs promotes earlier tumour formation on the plant host.

PMID- 22958120
TI  - Transjugular intrahepatic portosystemic shunt placement for refractory ascites: a
      single-centre experience.
AB  - BACKGROUND: The presence of refractory ascites is a common indication for
      transjugular intrahepatic portosystemic shunt (TIPS). Different models have been
      proposed for the prediction of survival after TIPS. The aim of this study was to
      evaluate the predictive factors associated with patients' survival after TIPS
      placement for refractory ascites. METHODS: Data from all consecutive patients
      undergoing TIPS placement in our center for refractory ascites between February
      2003 and January 2008 were prospectively recorded. RESULTS: Seventy-three
      patients (52M/21F; 57 +/- 10 years) met the inclusion criteria; mean follow-up
      was 17 +/- 2 months. Mean MELD value, before TIPS placement, was 15.7 +/- 5.3.
      TIPS placement led to an effective resolution of refractory ascites in 54% of
      patients (n = 40) with no significant increase in severe portosystemic
      encephalopathy. The 1-year survival rate observed was 65.7%, while the overall
      mortality was 23.3% (n = 17) with a mean survival of 17 +/- 14 months. MELD score
      (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B =
      0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B
      = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1
      year survival. ROC curves identified MELD >= 19 and HVPG >= 25 mmHg as the best
      cut-off points for the prediction of 1-year mortality. CONCLUSIONS: TIPS is an
      effective treatment for refractory ascites in cirrhotic patients, leading to an
      effective ascites control in more than half patients. Improvement in patients'
      selection criteria could lead to better outcome and survival after this
      procedure. Liver function (MELD), presence of active necroinflammation (AST), and
      portal hypertension (HVPG) are independent predictors of patients' outcome after
      TIPS.

PMID- 22958122
TI  - Faunistic catalog of the caddisflies (Insecta: Trichoptera) of Parque Nacional do
      Itatiaia and its surroundings in southeastern Brazil.
AB  - The Atlantic Forest is considered one of the world's biological diversity
      hotspots, and is increasingly threatened by the rapid destruction and
      fragmentation of its natural areas. The caddisflies (Trichoptera) of Itatiaia
      massif, an Atlantic Forest highland area, are inventoried and cataloged here. The
      catalog is based on examination of bibliographies, field work on many localities
      of Itatiaia massif (including Parque Nacional do Itatiaia - PNI), and the
      entomological collection Professor Jose Alfredo Pinheiro Dutra (DZRJ),
      Universidade Federal do Rio de Janeiro. A total of 92 species are recorded,
      representing about 17% of the known Brazilian Trichoptera fauna. Leptoceridae,
      Hydropsychidae, and Philopotamidae are the families most represented. The high
      species richness, as well as the remarkable patterns of species distribution, may
      be related to the characteristics of Mantiqueira mountain range.

PMID- 22958121
TI  - Occurrence and toxicity of disinfection byproducts in European drinking waters in
      relation with the HIWATE epidemiology study.
AB  - The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in
      drinking WATEr) project was a systematic analysis that combined the epidemiology
      on adverse pregnancy outcomes and other health effects with long-term exposure to
      low levels of drinking water disinfection byproducts (DBPs) in the European
      Union. The present study focused on the relationship of the occurrence and
      concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking
      water samples were collected from five European countries. Each sampling location
      corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs
      were identified; the range in the number of DBPs and their levels reflected the
      diverse collection sites, different disinfection processes, and the different
      characteristics of the source waters. For each sampling site, chronic mammalian
      cell cytotoxicity correlated highly with the numbers of DBPs identified and the
      levels of DBP chemical classes. Although there was a clear difference in the
      genotoxic responses among the drinking waters, these data did not correlate as
      well with the chemical analyses. Thus, the agents responsible for the genomic DNA
      damage observed in the HIWATE samples may be due to unresolved associations of
      combinations of identified DBPs, unknown emerging DBPs that were not identified,
      or other toxic water contaminants. This study represents the first to integrate
      quantitative in vitro toxicological data with analytical chemistry and human
      epidemiologic outcomes for drinking water DBPs.

PMID- 22958123
TI  - Submonomer synthesis of a hybrid peptoid-azapeptoid library.
AB  - We recently reported efficient conditions for the synthesis of N-azapeptoid
      libraries via the typical submonomer strategy of peptoid synthesis but that
      substitutes N-acyl hydrazides for primary amines as submonomers. Unfortunately,
      this approach is not applicable to the synthesis of mixed azapeptoid-peptoid
      libraries. When an oligomer containing an N-terminal side chain derived from an
      acyl hydrazide is bromoacetylated and treated with a primary amine, a chain
      terminating intramolecular ring-closure to form an oxadiazinone competes with the
      desired displacement of the bromide by the amine. Here we overcome this
      limitation and demonstrate that a hybrid peptoid-azapeptoid library derived from
      primary amines, acyl hydrazides, carbazates, and semicarbazides can be made
      efficiently using standard peptoid submonomer chemistry. We find that the
      unwanted, chain-terminating cyclization reaction is competitive with chain
      extension only when aryl acyl hydrazides are present. Alkyl or heteroaromatic
      acyl hydrazides do not cyclize under the conditions used for peptoid-azapeptoid
      synthesis. We also find that carbazates and semicarbazides work well for chain
      extension. Using primary amines, acyl hydrazides, carbazates, and semicarbazides
      as submonomers, a high-quality one bead one compound library of tetramers
      suitable for screening against protein targets was made by split and pool
      synthesis. 

PMID- 22958124
TI  - Gold biosorption by exopolysaccharide producing cyanobacteria and purple
      nonsulphur bacteria.
AB  - AIMS: This study was aimed at investigating the possible exploitation of
      phototrophic micro-organisms for the removal and the recovery of Au from Au
      containing wastewaters deriving from a plating industry. METHODS AND RESULTS: A
      screening among ten phototrophic micro-organisms was carried out with pure
      solutions of Au to select the best strain in terms of metal uptake and
      selectivity. The direct use of the selected micro-organism on the Au-containing
      industrial wastewater was then carried out with the aim of assessing the
      potential of its use for the removal and the recovery of the precious metal from
      industrial wastewaters. CONCLUSIONS: This study showed the good potential of some
      exopolysaccharide-producing cyanobacteria as biosorbents for the recovery of Au
      from wastewaters of plating industries but also pointed out the need to design an
      efficient technology for the recovery of the metal from the biomass. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The selection of good biosorbents for the recovery of
      gold from industrial wastewaters may open new perspectives to a green
      biotechnology so far considered too expensive for the mere treatment of
      wastewaters containing low valuable metals.

PMID- 22958126
TI  - First report on the whitefly, Aleurodicus pseudugesii on the coconut palm, Cocos
      nucifera in Brazil.
AB  - The coconut palm, Cocos nucifera L. (Arecales: Arecaceae), is currently grown
      extensively throughout the intertropical zones of the world, including Brazil,
      where it constitutes an important source of income for growers. Although
      whiteflies are not normally considered coconut pests, these insects can damage
      crops directly by sucking the sap, which weakens the plant; indirect damage may
      be caused by sooty mold formation over the excreted honeydew and by the
      transmission of pathogens. Whiteflies have infested coconut plants in the
      northeastern, northern, and southeastern regions of Brazil. Infested materials
      were collected and the causative insect was identified as Aleurodicus pseudugesii
      Martin (Hemiptera: Aleyrodidae). This is the first report of A. pseudugesii in
      Brazil as a pest of the coconut palm.

PMID- 22958125
TI  - Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and
      trichoepithelioma.
AB  - BACKGROUND: A recent small series demonstrated perfect sensitivity and
      specificity utilizing immunostaining for PHLDA1, a marker of follicular stem
      cells, in the distinction of desmoplastic trichoepithelioma and morphoeiform
      basal cell carcinoma (BCC) in small biopsy specimens. OBJECTIVES: To assess this
      result more broadly. METHODS: We performed immunoperoxidase staining of BCCs
      (superficial n = 16, nodular n = 15, micronodular n = 15, infiltrative n = 17,
      morphoeiform n = 16, infundibulocystic n = 14) and trichoepitheliomas
      (conventional n = 19, desmoplastic n = 16) with PHLDA1. RESULTS: Morphoeiform
      BCCs typically lacked PHLDA1 staining (88% demonstrated no staining and 12% of
      cases had staining in < 25% of the tumour), while in contrast 74% of classical
      and 88% of desmoplastic trichoepitheliomas demonstrated strong PHLDA1 staining in
      over half of the tumour. However, micronodular BCCs demonstrated focal to diffuse
      positive staining in a third of the cases. CONCLUSIONS: Based upon our staining
      results, we discuss the biological significance of PHLDA1 expression and the
      limits in its diagnostic utility.

PMID- 22958127
TI  - Differential investigations from plasma-derived and recombinant Factor IX
      revealed major differences in post-translational modifications of activation
      peptides.
AB  - Post-translational modifications (PTMs) located on the activation peptide (AP) of
      recombinant FIX (rFIX, BeneFIX((r)) ) and plasma-derived FIX (pdFIX,
      Betafact((r)) ) have been investigated by mass spectrometry to review the
      structural differences between these two products. Three major structural
      differences were pointed out. rFIX contains a low amount of phosphorylated and
      sulphated AP (4% for rFIX vs. 70% for pdFIX); rFIX N-glycans are only sialylated
      in the alpha2-3 linkage, whereas pdFIX N-glycans contain both type of alpha2-3
      and alpha2-6 linkages, and rFIX does not contain any sialyl Lewis(X) 
      glycoantigens contrary to pdFIX. These variations might participate in the in
      vivo potential different behaviours of the two molecules.

PMID- 22958128
TI  - Seizure worsening and its predictors after epilepsy surgery.
AB  - PURPOSE: This study aims to investigate seizure worsening and its predictors
      after epilepsy surgery. METHODS: A retrospective chart review of patients who
      underwent unilobar epilepsy surgery between 1990 and 2007 and had recurrence of
      at least one seizure was performed. Seizure worsening was defined as an increase
      in total average monthly seizure frequency, average monthly generalized tonic
      clonic seizures (GTCS), new-onset GTCS, or new-onset status epilepticus. The
      occurrence of sudden unexpected death in epilepsy (SUDEP) was captured.
      Multivariate logistic regression analysis was used to identify predictors of
      worsening. KEY FINDINGS: A total of 276 patients with postoperative seizure
      recurrence were identified. Monthly average seizure frequency worsening occurred
      in 9.8%, GTC worsening in 8.0%, new-onset GTCs in 1.4%, new-onset status
      epilepticus in 2.2%, and death from SUDEP in 1.4%. A higher risk of worsening was
      seen with extratemporal resections as compared to temporal lobe surgeries (odds
      ratio [OR] 3.11, 95% confidence interval [CI] 1.21-7.95; p = 0.018), and in
      patients with low preoperative seizure frequency <30 seizures/month (OR 14.82,
      95% CI 2.81-275.41; p = 0.0003). Predictors of increased GTCs included an
      incomplete resection (OR 3.98, 95% CI 1.39-12.59; p = 0.010) and multiple
      recorded ictal patterns (OR 5.91, 95% CI 1.20-26.96; p = 0.030). Multiple seizure
      semiologies correlated with worsening after temporal lobe resections.
      SIGNIFICANCE: The most vulnerable patients for seizure worsening following
      epilepsy surgery include those with extratemporal resections, incomplete
      resections, and multiple recorded ictal patterns.

PMID- 22958129
TI  - Synthesis of ionic liquid-supported sulfonyl azide and its application in
      diazotransfer reaction.
AB  - The paper describes synthesis of a novel ionic liquid-supported sulfonyl azide
      and its applications as diazotransfer reagent of active methylene compounds as
      well as deformylative diazo transfer reagent. The diazo compounds were isolated
      in excellent yields (82-94%) and high purity. The method offers better separation
      of product and reagent. This method is experimentally simple and mild, and
      requires very short reaction time.

PMID- 22958130
TI  - One if by land, two if by sea: signalling to the ranks with CSP and XIP.
AB  - In many streptococci, quorum sensing utilizes secreted, linear peptides that
      engage cognate receptors to coordinate gene expression among members of a local
      population. Streptococcus mutans employs the secreted peptides CSP and XIP to
      stimulate production of antimicrobial bacteriocins and to induce development of
      competence for genetic transformation. Recent progress in the field reveals that
      these pathways not only monitor the presence of signal emitters but also sense
      environmental factors. Both kinds of information are integrated by regulatory
      networks that then generate multiple outcomes, even among parallel cells growing
      in identical conditions. In this issue of Molecular Microbiology, Son and co
      workers investigate how two medium types shape cellular responses to CSP and XIP
      pheromones in individuals across a population. Their findings characterize
      restrictive properties of media differing in peptidic fragment content and reveal
      unusual signalling properties that contribute to bimodal responses of gene
      expression.

PMID- 22958131
TI  - Coexistence of Epstein-Barr virus-associated lymphoproliferative disorder and
      marginal zone B-cell lymphoma of the thymus in a patient with rheumatoid
      arthritis treated with methotrexate.

PMID- 22958132
TI  - Conjugation chemistry through acetals toward a dextran-based delivery system for
      controlled release of siRNA.
AB  - New conjugation chemistry for polysaccharides, exemplified by dextran, was
      developed to enable the attachment of therapeutic or other functional moieties to
      the polysaccharide through cleavable acetal linkages. The acid-lability of the
      acetal groups allows the release of therapeutics under acidic conditions, such as
      that of the endocytic compartments of cells, regenerating the original free
      polysaccharide in the end. The physical and chemical behavior of these acetal
      groups can be adjusted by modifying their stereoelectronic and steric properties,
      thereby providing materials with tunable degradation and release rates. We have
      applied this conjugation chemistry in the development of water-soluble siRNA
      carriers, namely acetal-linked amino-dextrans, with various amine structures
      attached through either slow- or fast-degrading acetal linker. The carriers with
      the best combination of amine moieties and structural composition of acetals
      showed high in vitro transfection efficiency and low cytotoxicity in the delivery
      of siRNA.

PMID- 22958133
TI  - Acute effect of ethanol on hepatic reticular G6Pase and Ca2+ pool.
AB  - BACKGROUND: Hydrolysis of glucose 6-phosphate (G6P) via glucose 6-phosphatase
      (G6Pase) enlarges the reticular Ca(2+) pool of the hepatocyte. Exposure of liver
      cells to ethanol (EtOH) impairs reticular Ca(2+) homeostasis. The present study
      investigated the effect of acute EtOH administration on G6P-supported Ca(2+)
      accumulation in liver cells. METHODS: Total microsomes were isolated from rat
      livers acutely perfused with varying doses of EtOH (0.01, 0.1, or 1% v/v) for 8
      minutes. Calcium uptake was assessed by (45) Ca redistribution. Inorganic
      phosphate (Pi) formation was measured as an indicator of G6Pase hydrolytic
      activity. RESULTS: G6P-supported Ca(2+) uptake decreased in a manner directly
      proportional to the dose of EtOH infused in the liver, whereas Ca(2+) uptake via
      SERCA pumps was decreased by ~25% only at the highest dose of alcohol
      administered. The reduced accumulation of Ca(2+) within the microsomes resulted
      in a smaller inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release. Kinetic
      assessment of IP(3) and passive Ca(2+) release indicated a faster mobilization in
      microsomes from EtOH-treated livers, suggesting alcohol-induced alteration of
      Ca(2+) releasing mechanisms. Pretreatment of livers with chloromethiazole (CMZ)
      or dithiothreitol (DTT), but not 4-methyl-pyrazole prevented the inhibitory
      effect of EtOH on G6Pase activity and Ca(2+) homeostasis. CONCLUSIONS: Liver
      G6Pase activity and IP(3) -mediated Ca(2+) release are rapidly inhibited
      following acute (8 minutes) exposure to EtOH, thus compromising the ability of
      the endoplasmic reticulum to dynamically modulate Ca(2+) homeostasis in the
      hepatocyte. The protective effect of CMZ and DTT suggests that the inhibitory
      effect of EtOH is mediated through its metabolism via reticular cyP4502E1 and
      consequent free radicals formation.

PMID- 22958135
TI  - Editorial Comment to tadalafil once daily for lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia: a randomized placebo- and tamsulosin
      controlled 12-week study in Asian men.

PMID- 22958134
TI  - Mechanism of photo-oxidation of heptafluorobutyric anhydride in the presence of
      NO2. Synthesis and characterization of heptafluoropropyl peroxynitrate,
      CF3CF2CF2OONO2.
AB  - The photolysis of heptafluorobutyric anhydride at 254 nm in the presence of NO(2)
      and O(2) has been studied. It leads to the formation of CF(3)CF(2)CF(2)OONO(2),
      CF(3)CF(2)OONO(2), and CF(2)O as the only fluorine-containing carbonaceous
      products. The formation of the new heptafluoropropyl peroxynitrate (HFPN,
      CF(3)CF(2)CF(2)OONO(2)), as one of the main products, is a consequence of the
      formation of CF(3)CF(2)CF(2)OO(*) radicals followed by the reaction with NO(2).
      To characterize HFPN, the UV absorption cross sections and their temperature
      dependence between 245 and 300 K have been measured over the wavelength range 200
      300 nm as well as the infrared absorption cross sections. Kinetic parameters for
      its thermal decomposition are also presented in the temperature range between 281
      and 300 K. The Rice-Ramsperger-Kassel-Marcus calculation reveals that the rate
      coefficient for the thermal decomposition at 285 K is almost independent of total
      pressure. The mechanism for the decomposition of CF(3)CF(2)CF(2)OONO(2) in the
      presence of NO was adjusted by a kinetic model, which enabled the calculation of
      important rate coefficients.

PMID- 22958136
TI  - Modifying the course of chronic obstructive pulmonary disease: looking beyond the
      FEV1.
AB  - COPD is defined by airflow limitation that is not fully reversible and is usually
      progressive. Thus, airflow obstruction (measured as FEV(1)) has traditionally
      been used as the benchmark defining disease modification with therapy. However,
      COPD exacerbations and extrapulmonary effects are common and burdensome and
      generally become more prominent as the disease progresses. Therefore, disease
      progression should be broader than FEV(1) alone. Interventions that reduce the
      frequency or severity of exacerbations or ameliorate extrapulmonary effects
      should also be considered disease modifiers. A narrow focus on FEV(1) will fail
      to capture all the beneficial effects of therapy on disease modification.
      Although smoking cessation has been unequivocally demonstrated to slow the rate
      of FEV(1) decline, inhaled corticosteroid-long-acting bronchodilator therapy may
      also have modest effects according to post hoc analysis. Maintenance
      pharmacotherapy with inhaled long-acting anti-muscarinic or beta-adrenergic
      agents or combined beta-adrenergic--inhaled corticosteroid reduces symptoms,
      improves lung function, reduces the frequency of exacerbations, and improves
      exercise capacity and HRQL. Pulmonary rehabilitation reduces symptom burden,
      increases exercise capacity, improves HRQL, and reduces health care utilization,
      probably through reducing the severity of exacerbations. Smoking cessation, lung
      volume reduction surgery, inhaled maintenance pharmacotherapy, and pulmonary
      rehabilitation administered in the post-exacerbation period may reduce mortality
      in COPD. These improvements over multiple outcome areas and over relatively long
      durations suggest that disease modification is indeed possible with existing
      therapies for COPD. Therefore, therapeutic nihilism in COPD is no longer
      warranted.

PMID- 22958137
TI  - Thermally induced degradation of aliphatic glucosinolates: identification of
      intermediary breakdown products and proposed degradation pathways.
AB  - In  Brassica  vegetables, heating processes lead to thermally induced degradation
      of glucosinolates (GSLs), resulting in the formation of nitriles and
      isothiocyanates (ITCs). To date, the mechanism is not yet satisfyingly
      elucidated. Thermally induced degradation of the model GSL sinigrin was studied
      in dry as well as aqueous medium at different pH values and temperatures. The
      influence of the presence of iron ions and plant matrix (broccoli sprouts powder)
      on the degradation was studied as well. Next to the degradation of the GSL, the
      formation of nitrile and ITC and the release of sugar derivatives were
      investigated. Because d-glucose and ITC are main thermal breakdown products under
      aqueous conditions, hydrolysis seems to be the initial step in the degradation
      pathway during cooking. In contrast, under dry conditions, the desulfo-sinigrin
      was identified as a main intermediary thermal breakdown product for the first
      time. Further, degradation of the desulfo-GSL results in the release of d
      thioglucose and the corresponding nitrile. Iron(II) ions and plant matrix
      influence the thermal stability of the GSL and favor the formation of nitriles.

PMID- 22958138
TI  - Impact of multiple joint impairments on the energetics and mechanics of walking
      in patients with haemophilia.
AB  - Few studies have assessed the changes produced by multiple joint impairments
      (MJI) of the lower limbs on gait in patients with haemophilia (PWH). In patients
      with MJI, quantifiable outcome measures are necessary if treatment benefits are
      to be compared. This study was aimed at observing the metabolic cost, mechanical
      work and efficiency of walking among PWH with MJI and to investigate the
      relationship between joint damage and any changes in mechanical and energetic
      variables. This study used three-dimensional gait analysis to investigate the
      kinematics, cost, mechanical work and efficiency of walking in 31 PWH with MJI,
      with the results being compared with speed-matched values from a database of
      healthy subjects. Regarding energetics, the mass-specific net cost of transport
      (C(net)) was significantly higher for PWH with MJI compared with control and
      directly related to a loss in dynamic joint range of motion. Surprisingly,
      however, there was no substantial increase in mechanical work, with PWH being
      able to adopt a walking strategy to improve energy recovery via the pendulum
      mechanism. This probable compensatory mechanism to economize energy likely
      counterbalances the supplementary work associated with an increased vertical
      excursion of centre of mass (CoM) and lower muscle efficiency of locomotion.
      Metabolic variables were probably the most representative variables of gait
      disability for these subjects with complex orthopaedic degenerative disorders.

PMID- 22958139
TI  - Organocatalytic asymmetric synthesis of 3-chlorooxindoles bearing adjacent
      quaternary-tertiary centers.
AB  - A new methodology was developed for the synthesis of enantiomerically enriched
      3,3-disubstituted 3-chlorooxindoles 3 via a Michael addition of 3-chloroxindoles
      to nitroolefins 2, catalyzed by chiral squaramide 10. Products with adjacent
      quaternary-tertiary centers were isolated in excellent yields (up to 99%), high
      diastereoselectivities (up to 11:1), and enantiomeric purities (up to 92%). This
      is the first example where 3-chloroxoindoles 1 have been used as nucleophiles in
      a highly stereoselective organocatalytic reaction.

PMID- 22958140
TI  - "There are too many steps before you get to where you need to be": help-seeking
      by patients with first-episode psychosis.
AB  - BACKGROUND: There has been substantial research on pathways to care in first
      episode psychosis (FEP); however, few studies have used a qualitative research
      paradigm or have been done from the perspective of the person experiencing the
      psychotic episode. OBJECTIVE: We sought to describe the experiences of patients
      with FEP on their pathway to care and to identify factors that help or hinder
      help-seeking efforts. METHODS: Using a qualitative descriptive approach, we
      conducted semi-structured interviews with 16 patients recruited from an early
      intervention program. Data were analyzed using content analysis to organize the
      findings into themes. FINDINGS: Self-stigma and a pervasive lack of knowledge
      regarding the symptoms of psychosis and availability of services were barriers to
      help-seeking. Participants highlighted the crucial role of significant others in
      initiating the help-seeking process. Participants typically described a complex
      series of contacts along the pathway to care which resulted in feelings of being
      misunderstood and losing control, but many individuals identified unexpected
      benefits of their experience. CONCLUSIONS: Our findings suggest a shift in the
      philosophy and orientation of service delivery towards the creation of services
      that address these concerns and are relevant to the young people who utilize
      them.

PMID- 22958141
TI  - Impressive pseudotumoral proliferative nodules in a giant congenital nevus of a
      newborn.
AB  - The potential for malignant transformation of a giant congenital melanocytic
      nevus (GCMN), although rare, should be considered, especially in proliferative
      lesions that have nodules on their surface, as they can clinically and
      histologically mimic melanoma and generally have a poor prognosis. We present the
      case of a newborn boy with a giant nevus of uneven blackish color on the back
      with variable degrees of intensity of pigmentation, almost entirely covered by
      nodules of large and variable sizes, soft texture, and a tendency to ulcerate and
      bleed. The unusual clinical and histologic appearance made the case particularly
      interesting and featured a not well-defined biologic behavior, thus deserving a
      radical surgical approach to fulfill diagnostic and therapeutic aims.

PMID- 22958142
TI  - Integration of computer and Internet-based programmes into psychiatric out
      patient care of adolescents with depression.
AB  - The aim of this explorative study was to describe nurses' opportunities to
      integrate computer and Internet-based programmes in psychiatric out-patient care
      among adolescents with depression. Therefore, nurses' daily computer use and
      possible problems related to it were investigated. The data were collected by
      conducting focus group interviews with Finnish registered nurses (n =12) working
      at the out-patient clinics of two university central hospitals. The data were
      analysed using inductive content analysis. The analysis showed that nurses used
      the computer and Internet in their daily work for data transmission and informal
      interaction with adolescents. Findings revealed that nurses have good computer
      skills, a positive attitude towards using the computer and Internet and were
      motivated to make use of both on a daily basis. Problems faced in daily computer
      use were a lack of instructions and education, and lack of help and support. We
      can conclude that nurses have good opportunities to implement computer and
      Internet-based programmes in adolescent out-patient care. These results are
      encouraging keeping in mind that adolescents are the most active Internet users
      in society.

PMID- 22958143
TI  - Influence of bacterial extracellular polymeric substances on the formation of
      carbonaceous and nitrogenous disinfection byproducts.
AB  - Considering the regulatory presence of residual chlorine in water distribution
      systems, untreated organic matter may not be the sole contributor to disinfection
      byproduct (DBP) formation, given the presence of microbial biofilm with
      extracellular polymeric substances (EPS). This study investigated the influence
      of bacterial EPS on the formation of carbonaceous DBPs (C-DBPs) and nitrogenous
      DBPs (N-DBPs), reacting chlorine with Pseudomonas strains that produce different
      quantities and composition of EPS. When biomass is reacted in excess to chlorine,
      both C-DBPs and N-DBPs were produced without preference for speciation. However,
      under an excess of chlorine compared to biomass, increased EPS content led to
      enhanced formation of DBPs. The DBP yield of haloacetic acids (HAAs) was higher
      than that of trihalomethanes where dichloroacetic acid was dominant in HAA
      species. Additionally, chemical composition of EPS influenced the yields of DBPs.
      The N-DBP yield from P. putida EPS was two times higher than that of P.
      aeruginosa EPS, which suggested that higher organic nitrogen content in EPS
      contributes to higher N-DBP yield. Moreover, time-based experiments revealed that
      DBP formation from biomass occurs rapidly, reaching a maximum in less than four
      hours. Combined results suggest that bacterial EPS have significant roles in both
      the formation and fate of DBPs.

PMID- 22958144
TI  - Periodontal ligament cells cultured under steady-flow environments demonstrate
      potential for use in heart valve tissue engineering.
AB  - A major drawback of mechanical and prosthetic heart valves is their inability to
      permit somatic growth. By contrast, tissue-engineered pulmonary valves
      potentially have the capacity to remodel and integrate with the patient. For this
      purpose, adult stem cells may be suitable. Previously, human periodontal ligament
      cells (PDLs) have been explored as a reliable and robust progenitor cell source
      for cardiac muscle regeneration (Pelaez, D. Electronic Thesis and Dissertation
      Database, Coral Gables, FL, May 2011). Here, we investigate the potential of PDLs
      to support the valve lineage, specifically the concomitant differentiation to
      both endothelial cell (EC) and smooth muscle cell (SMC) types. We were able to
      successfully promote PDL differentiation to both SMC and EC phenotypes through a
      combination of stimulatory approaches using biochemical and mechanical flow
      conditioning (steady shear stress of 1 dyne/cm(2)), with flow-based mechanical
      conditioning having a predominant effect on PDL differentiation, particularly to
      ECs; in addition, strong expression of the marker FZD2 and an absence of the
      marker MLC1F point toward a unique manifestation of smooth muscle by PDLs after
      undergoing steady-flow mechanical conditioning alone, possible by only the heart
      valve and pericardium phenotypes. It was also determined that steady flow (which
      was performed using a physiologically relevant [for heart valves] magnitude of ~5
      6 dynes/cm(2)) augmented the synthesis of the extracellular matrix collagen
      proteins. We conclude that under steady-flow dynamic culture environments, human
      PDLs can differentiate to heterogeneous cell populations that are relevant to
      heart valve tissue engineering. Further exploration of human PDLs for this
      purpose is thus warranted.

PMID- 22958145
TI  - Multiparameter cell affinity chromatography: separation and analysis in a single
      microfluidic channel.
AB  - The ability to sort and capture more than one cell type from a complex sample
      will enable a wide variety of studies of cell proliferation and death and the
      analysis of disease states. In this work, we integrated a pneumatic actuated
      control layer to an affinity separation layer to create different antibody
      coating regions on the same fluidic channel. The comparison of different antibody
      capture capabilities to the same cell line was demonstrated by flowing Ramos
      cells through anti-CD19- and anti-CD71-coated regions in the same channel. It was
      determined that the cell capture density on the anti-CD19 region was 2.44 +/-
      0.13 times higher than that on the anti-CD71-coated region. This approach can be
      used to test different affinity molecules for selectivity and capture efficiency
      using a single cell line in one separation. Selective capture of Ramos and HuT 78
      cells from a mixture was also demonstrated using two antibody regions in the same
      channel. Greater than 90% purity was obtained on both capture areas in both
      continuous flow and stop flow separation modes. A four-region antibody-coated
      device was then fabricated to study the simultaneous, serial capture of three
      different cell lines. In this case the device showed effective capture of cells
      in a single separation channel, opening up the possibility of multiple cell
      sorting. Multiparameter sequential blood sample analysis was also demonstrated
      with high capture specificity (>97% for both CD19+ and CD4+ leukocytes). The chip
      can also be used to selectively treat cells after affinity separation.

PMID- 22958146
TI  - Gastrointestinal disorders and dabigatran.
AB  - Anticoagulants play an important role in the prevention and treatment of a
      variety of acute and chronic thromboembolic disorders such as primary prevention
      and treatment of venous thromboembolism or prevention of stroke and systemic
      embolism in atrial fibrillation just to name of few. Within recent years, a
      promising new oral anticoagulant, the direct thrombin inhibitor dabigatran
      etexilate (dabigatran) successfully underwent clinical development and has
      emerged as an alternative to vitamin K antagonists according to a variety of
      recently revised and updated international guidelines referring to the indication
      of stroke prevention in atrial fibrillation. Considering the intensive clinical
      use of vitamin K antagonists in the mentioned indication as well as the
      widespread and increasing therapeutic need on one hand and the likely
      availability of a more efficacious alternative with fewer limitations in clinical
      practice on the other, there is good reason to assume that the use of dabigatran
      may be broad within the general medical community in the near future. Based on
      what is currently published in the public domain and clinical trial data it is
      suggested that dabigatran etexilate is associated with higher rates of dyspeptic
      symptoms compared to warfarin. Therefore, it is the authors' intent to review and
      discuss this potential dyspeptic side effect profile of dabigatran and potential
      counter measures from a gastroenterologist's perspective.

PMID- 22958147
TI  - Projections of future extreme weather losses under changes in climate and
      exposure.
AB  - Many attempts are made to assess future changes in extreme weather events due to
      anthropogenic climate change, but few studies have estimated the potential change
      in economic losses from such events. Projecting losses is more complex as it
      requires insight into the change in the weather hazard but also into exposure and
      vulnerability of assets. This article discusses the issues involved as well as a
      framework for projecting future losses, and provides an overview of some state-of
      the-art projections. Estimates of changes in losses from cyclones and floods are
      given, and particular attention is paid to the different approaches and
      assumptions. All projections show increases in extreme weather losses due to
      climate change. Flood losses are generally projected to increase more rapidly
      than losses from tropical and extra-tropical cyclones. However, for the period
      until the year 2040, the contribution from increasing exposure and value of
      capital at risk to future losses is likely to be equal or larger than the
      contribution from anthropogenic climate change. Given the fact that the
      occurrence of loss events also varies over time due to natural climate
      variability, the signal from anthropogenic climate change is likely to be lost
      among the other causes for changes in risk, at least during the period until
      2040. More efforts are needed to arrive at a comprehensive approach that includes
      quantification of changes in hazard, exposure, and vulnerability, as well as
      adaptation effects.

PMID- 22958148
TI  - Epidemiology and diagnosis of Helicobacter pylori infection.
AB  - Medline, PubMed and the Cochrane databases were searched on epidemiology and
      diagnosis of Helicobacter pylori for the period of April 2011-March 2012. Several
      studies have shown that the prevalence of H. pylori infection is decreasing in
      adults and children in many countries. Various diagnostic tests are available,
      and most of them have high sensitivity and specificity. The Maastricht
      IV/Florence consensus report states that the urea breath test using (13)C urea
      remains the best test to diagnose H. pylori infection. Among the stool antigen
      tests, the ELISA monoclonal antibody test is recommended. All these tests were
      used, either as a single diagnostic test or in combination, to investigate H.
      pylori infection among different populations throughout the world. Of particular
      interest, current improvements in high-resolution endoscopic technologies enable
      increased diagnostic accuracy for the detection of H. pylori infection, but none
      of these techniques, at present, are specific enough for obtaining a real-time
      diagnosis of H. pylori infection.

PMID- 22958149
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Although Helicobacter pylori infection is highly prevalent in the global human
      population, the majority of infected individuals remain asymptomatic. A complex
      combination of host, environmental, and bacterial factors are considered to
      determine susceptibility and severity of outcome in the subset of individuals
      that develop clinical disease. These factors collectively determine the ability
      of H. pylori to colonize the gastric mucosa and profoundly influence the nature
      of the interaction that ensues. Many studies over the last year provide new
      insight into H. pylori virulence strategies and the activities of critical
      bacterial determinants that modulate the host environment. These latter include
      the secreted proteins CagA and VacA and adhesins BabA and OipA, which directly
      interact with host tissues. Observations from several studies extend the
      functional repertoire of CagA and the cag type IV secretion system in particular,
      providing further mechanistic understanding of how these important determinants
      engage and activate host signalling pathways important in the development of
      disease.

PMID- 22958150
TI  - Inflammation, immunity, and vaccines for Helicobacter pylori infection.
AB  - The immune response to Helicobacter pylori is a multifaceted group of mechanisms
      involving responses that are both protective and damaging to the host. The innate
      and the adaptive immune responses lead to damaging inflammatory responses, but
      these responses may fail, allowing for persistence of many infections. Thus,
      developing new therapeutics and effective vaccines against H. pylori has proven
      to be arduous. In this manuscript, we will examine the advances in knowledge made
      in the past year in understanding the host immune response to H. pylori and the
      progress toward developing a vaccine.

PMID- 22958151
TI  - Helicobacter pylori and nonmalignant diseases.
AB  - The incidence of peptic ulcer disease has declined over the last few decades,
      particularly in Western populations, most likely as a result of the decrease in
      Helicobacter pylori infection and the widespread use of proton-pump inhibitors
      (PPI) in patients with dyspepsia. The hospital admission rate for uncomplicated
      duodenal and gastric ulcers has significantly decreased worldwide. In contrast,
      admissions for complicated ulcer disease, such as bleeding peptic ulcers and
      perforation, remained relatively stable. Prophylactic H. pylori eradication was
      found to be associated with a reduced risk of both gastric and duodenal ulcers
      and their complications, including bleeding in chronic users of nonsteroidal anti
      inflammatory drugs. The recent Helicobacter Eradication Relief of Dyspeptic
      Symptoms trial presented important data relating to symptoms and quality of life
      of H. pylori-positive patients with functional dyspepsia (FD) and also
      demonstrated significant benefits from eradication compared with the control
      group. The new Asian consensus report on FD recommended that dyspepsia
      accompanied by H. pylori infection should be considered a separate disease entity
      from FD and that H. pylori infection should be eradicated before diagnosing FD.
      The association of H. pylori with gastroesophageal reflux disease (GERD) is still
      controversial. Treatment for H. pylori does not seem to increase GERD symptoms or
      reflux esophagitis. However, documented eradication of H. pylori appears to
      significantly improve GERD symptoms. Additional long-term intervention studies
      are needed to provide more information on which to base clinical decisions.

PMID- 22958152
TI  - Gastric cancer: basic aspects.
AB  - The worldwide incidence and mortality of gastric cancer (GC) remain high, and new
      concepts for diagnosis and treatment are needed. In this review, we summarize
      recent studies that applied next-generation sequencing approaches and also report
      the latest development in microRNA research. Two recently published studies
      identified somatic mutations in ARID1A gene in GC using exome sequencing. On the
      other hand, dysregulation of microRNA expression can alter processes such as
      proliferation, apoptosis, invasion, and metastasis. These novel markers may prove
      to be useful in earlier diagnosis and as prognostic or predictive markers in
      patients with GC .

PMID- 22958153
TI  - Helicobacter pylori: gastric cancer and extragastric intestinal malignancies.
AB  - The greatest challenge in Helicobacter pylori-related diseases continues to
      remain prevention of gastric cancer. New evidence supports the beneficial effect
      of H. pylori eradication not only on prevention of gastric cancer but also on the
      regression of preneoplastic conditions of the gastric mucosa. Concerning early
      detection of gastric cancer there are still no adequate means and there is urgent
      need to define appropriate markers, for example, by genome-wide research
      approaches. Currently, the best available method is the "serologic" biopsy based
      on pepsinogen I and the pepsinogen I/II ratio for identification of patients with
      severe gastric atrophy at increased risk for gastric cancer development. The
      treatment of early gastric cancer by endoscopic techniques can be performed
      safely and efficiently, but patients need meticulous follow-up for detection of
      metachronous lesions. In case of advanced disease, laparoscopically assisted
      surgical procedures are safe and favorable compared to open surgery. Two phase
      III trials support the role of adjuvant systemic treatment with different
      regimens. Unfortunately, there is still only slow progress in the development of
      palliative treatment regimens or modification of the existing therapy protocols.
      There is accumulating evidence for a role of H. pylori infection also in
      colorectal carcinogenesis. Seropositive individuals are at higher risk for the
      development of colorectal adenomas and consequently adenocarcinomas of this
      anatomical region. This phenomenon can partly be attributed to the increase of
      serum gastrin as response to atrophic changes of the gastric mucosa.

PMID- 22958154
TI  - Treatment of Helicobacter pylori infection 2012.
AB  - Helicobacter pylori resistance rates to antibiotics vary in different countries
      and even in different regions of the same country. Choice of treatment is
      strongly dependent on antibiotic resistance rates. In some countries, triple
      therapy with a proton-pump inhibitor, amoxicillin, and clarithromycin is still
      the best option, but eradication results fall short of what would be desired (90
      95%) in countries with clarithromycin resistance >20%, bismuth-containing
      quadruple therapy, or nonbismuth sequential or concomitant therapies may then be
      the preferred option. Newer antibiotic regimens are awaited. Vaccination would be
      the best option, especially for developing countries, but little progress has
      been made in designing a vaccine.

PMID- 22958155
TI  - Helicobacter pylori in pediatrics.
AB  - This review summarizes important pediatric studies published from April 2011 up
      to March 2012. Proteomics profile of ulcerogenic Helicobacter pylori strains was
      defined in the most interesting study of the last year. The antigen stool test is
      becoming the "gold standard" in prevalence studies, and according to the last
      epidemiologic studies, the prevalence of H. pylori infection in childhood is not
      decreasing any more in the developed world. The resistance rate of H. pylori
      strains is high in children. Therefore, among other important issues concerning
      H. pylori in pediatrics, guidelines published by ESPGHAN and NASPGHAN last year
      also recommended culture and susceptibility testing before first-line treatment
      in areas with high or unknown antibiotic resistance rates.

PMID- 22958156
TI  - Extragastric manifestations of Helicobacter pylori infection.
AB  - In the last year, different diseases possibly linked to Helicobacter pylori
      infection but localized outside of the stomach have been investigated. There are,
      in fact, several studies concerning cardiovascular diseases, hematologic
      disorders, neurologic diseases, metabolic, hepatobiliary diseases, and other
      conditions. Some of those studies, such as those on sideropenic anemia and
      idiopathic thrombocytopenic purpura, are quite large and well conducted, while in
      other cases there are just small or isolated studies or even case reports.
      Nonetheless, there is much interest among researchers all over the world for such
      a topic as demonstrated by the large number of studies published in the last
      year.

PMID- 22958157
TI  - Helicobacter spp. other than H. pylori.
AB  - Significant advances have been made over the last 12 months in the understanding
      of the biology of non-H. pylori Helicobacter species (NHPH). Several studies have
      investigated the association between NHPH and human disease, including Crohn's
      disease, lithiasis, liver disease, coronary disease, gastritis, and pyoderma
      gangrenosum-like ulcers. Novel Helicobacter taxa were identified in new
      vertebrate hosts, and new methodologies in the fields of identification of
      Helicobacter spp. and evaluation of antibiotic resistance were described. The
      genome of the first human-derived gastric NHPH strain (Helicobacter bizzozeronii
      CIII-1) was sequenced, and several studies elucidated functions of different
      genes in NHPH. A number of important investigations regarding pathogenesis and
      immunopathobiology of NHPH infections have been published including the
      description of a new urease in Helicobacter mustelae. Finally, the effects of the
      gut microbiota and probiotics on NHPH infections were investigated.

PMID- 22958159
TI  - Molecular-scale and wide-energy-range tunneling spectroscopy on self-assembled
      monolayers of alkanethiol molecules.
AB  - The electronic properties of alkanethiol self-assembled monolayers
      (alkanethiolate SAMs) associated with their molecular-scale geometry are
      investigated using scanning tunneling microscopy and spectroscopy (STM/STS). We
      have selectively formed the three types of alkanethiolate SAMs with standing-up,
      lying-down, and lattice-gas phases by precise thermal annealing of the SAMs which
      are conventionally prepared by depositing alkanethiol molecules onto Au(111)
      surface in solution. The empty and filled states of each SAM are evaluated over a
      wide energy range covering 6 eV above/below the Fermi level (E(F)) using two
      types of STS on the basis of tunneling current-voltage and distance-voltage
      measurements. Electronic states originating from rigid covalent bonds between the
      thiol group and substrate surface are observed near E(F) in the standing-up and
      lying-down phases but not in the lattice-gas phase. These states contribute to
      electrical conduction in the tunneling junction at a low bias voltage. At a
      higher energy, a highly conductive state stemming from the alkyl chain and an
      image potential state (IPS) formed in a vacuum gap appear in all phases. The IPS
      shifts toward a higher energy through the change in the geometry of the SAM from
      the standing-up phase to the lattice-gas phase through the lying-down phase. This
      is explained by the increasing work function of alkanethiolate/Au(111) with
      decreasing density of surface molecules.

PMID- 22958160
TI  - Effect of adjunctive viscogonioplasty on drainage angle status in cataract
      surgery: a randomized clinical trial.
AB  - BACKGROUND: To compare the anatomic effects of phacoemulsification (Phaco) versus
      combined phacoemulsification and viscogonioplasty (Phaco-VGP) on drainage angle
      status in primary angle-closure glaucoma (PACG) using anterior segment optical
      coherence tomography (AS-OCT). DESIGN: Prospective, randomized clinical trial.
      PARTICIPANTS: Sixty-seven eyes of 57 patients with the diagnosis of PACG. METHOD:
      Patients were randomized to undergo Phaco alone (33 eyes) or Phaco-VGP (34 eyes).
      Patients were examined postoperatively on day 1, week 1 and week 6. Indentation
      gonioscopy and AS-OCT were performed preoperatively and at 6 weeks after surgery.
      MAIN OUTCOME MEASURES: Angle and anterior segment parameters by AS-OCT and amount
      of peripheral anterior synechiae (PAS) by gonioscopy. RESULTS: Sixty-five eyes of
      55 patients completed the trial. The mean extent of PAS was significantly reduced
      from 127.7 to 95.0 degrees (P < 0.001) by Phaco alone, and from 174.0 to 77.3
      degrees (P < 0.001) by Phaco-VGP. Phaco-VGP resulted in significantly greater
      reduction in PAS extent (P = 0.002). Angle-opening distance and trabecular-iris
      space-area measured by AS-OCT increased significantly after Phaco alone and Phaco
      VGP (P < 0.001 for both). Although the change was higher in the Phaco-VGP group,
      this did not reach statistical significance. Anterior chamber depth (ACD)
      increased, and lens vault (LV) decreased after both procedures. The amount of
      change in ACD and LV was not significant between the two groups. CONCLUSION: Both
      Phaco alone and Phaco-VGP resulted in widening of the drainage angle, deepening
      of the anterior chamber and reduction of intraocular pressure (IOP) and PAS
      extent in PACG eyes. Phaco-VGP resulted in significantly more reduction of PAS.
      However, it seems that additional VGP has no significant effect on short-term
      IOP.

PMID- 22958161
TI  - Differentiated functions of Ras1 and Ras2 proteins in regulating the germination,
      growth, conidiation, multi-stress tolerance and virulence of Beauveria bassiana.
AB  - Ras1 and Ras2 are two distinct Ras GTPases in Beauveria bassiana, an
      entomopathogenic fungus whose biocontrol potential against insect pests depends
      largely on virulence and multi-stress tolerance. The functions of both proteins
      were characterized for the first time by constructing dominant-active (GTP-bound)
      Ras1(G19V)  and dominant-negative (GDP-bound) Ras1(D126A)  and integrating them
      and normal Ras1 into wild type and DeltaRas2 for a series of phenotypic and
      transcriptional analyses. The resultant mutants showed gradient changes of
      multiple phenotypes but little difference in conidial thermotolerance. Expression
      of Ras1(D126A)  caused vigorous hyphal growth, severely defective conidiation,
      and increased tolerances to oxidation, cell wall disturbance, fungicide and UV
      A/UV-B irradiations, but affected slightly germination, osmosensitivity and
      virulence. These phenotypes were antagonistically altered by mRas1(G19V) 
      expressed in either wild type or DeltaRas2, which was severely defective in
      conidial germination and hyphal growth and displayed intermediate changes in
      other mentioned phenotypes between paired mutants expressing Ras1(G19V)  or
      Ras1(D126A)  in wild type and DeltaRas2. Their growth, UV tolerance or virulence
      was significantly correlated with cellular response to oxidation or cell wall
      disturbance. Transcriptional changes of 35 downstream effector genes involved in
      conidiation and multi-stress responses also related to most of the phenotypic
      changes among the mutants. Our findings highlight that Ras1 and Ras2 regulate
      differentially or antagonistically the germination, growth, conidiation, multi
      stress tolerance and virulence of B. bassiana, thereby exerting profound effects
      on the fungal biocontrol potential.

PMID- 22958162
TI  - Hearing the voices of service user researchers in collaborative qualitative data
      analysis: the case for multiple coding.
AB  - BACKGROUND: Health research is frequently conducted in multi-disciplinary teams,
      with these teams increasingly including service user researchers. Whilst it is
      common for service user researchers to be involved in data collection--most
      typically interviewing other service users--it is less common for service user
      researchers to be involved in data analysis and interpretation. This means that a
      unique and significant perspective on the data is absent. AIM: This study aims to
      use an empirical report of a study on Cognitive Behavioural Therapy for psychosis
      (CBTp) to demonstrate the value of multiple coding in enabling service users
      voices to be heard in team-based qualitative data analysis. DESIGN: The CBTp
      study employed multiple coding to analyse service users' discussions of CBT for
      psychosis (CBTp) from the perspectives of a service user researcher, clinical
      researcher and psychology assistant. Multiple coding was selected to enable
      multiple perspectives to analyse and interpret data, to understand and explore
      differences and to build multi-disciplinary consensus. RESULTS: Multiple coding
      enabled the team to understand where our views were commensurate and
      incommensurate and to discuss and debate differences. Through the process of
      multiple coding, we were able to build strong consensus about the data from
      multiple perspectives, including that of the service user researcher. DISCUSSION:
      Multiple coding is an important method for understanding and exploring multiple
      perspectives on data and building team consensus. This can be contrasted with
      inter-rater reliability which is only appropriate in limited circumstances.
      CONCLUSION: We conclude that multiple coding is an appropriate and important
      means of hearing service users' voices in qualitative data analysis.

PMID- 22958164
TI  - Effects of sublethal concentrations of the chitin synthesis inhibitor,
      hexaflumuron, on the development and hemolymph physiology of the cutworm,
      Spodoptera litura.
AB  - The effects of sublethal concentrations 0.1, 0.5, and 1.2 ug mL(-1)of the chitin
      synthesis inhibitor, hexaflumuron, on larval growth and development, the count
      and proportion of hemocytes, and carbohydrate content (trehalose and glyceride)
      in hemolymph were investigated in the cutworm, Spodoptera litura (Fabricious)
      (Lepidoptera: Noctuidae). When 3(rd) instar larvae were subjected to the
      sublethal concentrations, there were dose-dependent effects on larval weight and
      length of each instar larvae, percent pupation and the duration of development.
      Most of the larvae died during the molting process at all concentrations. Few
      individuals from 0.5 and 1.2 ug mL(-1)concentrations could develop to the 6(th)
      instar, while the pupae emerging from the 0.1 ug mL(-1)concentrations did not
      exceed 16% of the number of the initial larvae. In 5(th)instar S. litura, the
      total number of hemocytes was significantly increased at 24 hours post-treatment,
      whereas the proliferation of hemocytes was inhibited, plasmatocyte pseudopodia
      contracted, and granulocyte expanded at 96 hours post-treatment. The increases of
      plasmatocyte count and the decreases of granulocyte count were dose-dependent.
      The longer treatment time of the sublethal concentrations increased the content
      of total carbohydrate and trehalose in hematoplasma, and was dose-dependent in
      hemocytes. The content of glyceride in hemolymph was significantly higher at 24
      hours post-treatment, but gradually returned to normal levels at 96 hours post
      treatment as compared with the control. The results suggested that sublethal
      concentrations of hexaflumuron reduced S. litura larval survival and interfered
      with hemolymph physiological balances.

PMID- 22958165
TI  - Electrophoresis of fd-virus particles: experiments and an analysis of the effect
      of finite rod lengths.
AB  - The electrophoretic mobility of rodlike fd viruses is measured and compared to
      theory, with the theoretical calculations performed according to Stigter
      (Stigter, D. Charged Colloidal Cylinder with a Gouy Double-Layer. J. Colloid
      Interface Sci. 1975, 53, 296-306. Stigter, D. Electrophoresis of Highly Charged
      Colloidal Cylinders in Univalent Salt- Solutions. 1. Mobility in Transverse
      Field. J. Phys. Chem. 1978, 82, 1417-1423. Stigter, D. Electrophoresis of Highly
      Charged Colloidal Cylinders in Univalent Salt Solutions. 2. Random Orientation in
      External Field and Application to Polyelectrolytes. J. Phys. Chem. 1978, 82, 1424
      1429. Stigter, D. Theory of Conductance of Colloidal Electrolytes in Univalent
      Salt Solutions. J. Phys. Chem. 1979, 83, 1663-1670), who describes the
      electrophoretic mobility of infinite cylinders including relaxation effects.
      Using the dissociation constants of the ionizable groups on the surfaces of the
      fd viruses, we can calculate the mobility without any adjustable parameter (apart
      from the possible Stern layer thickness). In addition, the approximation in the
      theoretical description of Stigter (and others) of using a model of infinitely
      long cylinders, which consequently is independent of the aspect ratio, is
      examined by performing more elaborate numerical calculations for finite
      cylinders. It is shown that, although the electrophoretic mobility of cylindrical
      particles in the limit of low ionic strength depends on the aspect ratio much
      more than "end effects", at moderate and high ionic strengths the finite and
      infinite cylinder models differ only to a degree that can be attributed to end
      effects. Furthermore, the range of validity of the Stokes regime is
      systematically calculated.

PMID- 22958163
TI  - Magnetic resonance angiography-defined intracranial vasculopathy is associated
      with silent cerebral infarcts and glucose-6-phosphate dehydrogenase mutation in
      children with sickle cell anaemia.
AB  - Silent cerebral infarct (SCI) is the most commonly recognized cause of
      neurological injury in sickle cell anaemia (SCA). We tested the hypothesis that
      magnetic resonance angiography (MRA)-defined vasculopathy is associated with SCI.
      Furthermore, we examined genetic variations in glucose-6-phosphate dehydrogenase
      (G6PD) and HBA (alpha-globin) genes to determine their association with
      intracranial vasculopathy in children with SCA. Magnetic resonance imaging (MRI)
      of the brain and MRA of the cerebral vasculature were available in 516 paediatric
      patients with SCA, enrolled in the Silent Infarct Transfusion (SIT) Trial. All
      patients were screened for G6PD mutations and HBA deletions. SCI were present in
      41.5% (214 of 516) of SIT Trial children. The frequency of intracranial
      vasculopathy with and without SCI was 15.9% and 6.3%, respectively (P < 0.001).
      Using a multivariable logistic regression model, only the presence of a SCI was
      associated with increased odds of vasculopathy (P = 0.0007, odds ratio (OR) 2.84;
      95% Confidence Interval (CI) = 1.55-5.21). Among male children with SCA, G6PD
      status was associated with vasculopathy (P = 0.04, OR 2.78; 95% CI = 1.04-7.42),
      while no significant association was noted for HBA deletions. Intracranial
      vasculopathy was observed in a minority of children with SCA, and when present,
      was associated with G6PD status in males and SCI.

PMID- 22958166
TI  - Aggressive behavior and epilepsy: a multicenter study.
AB  - The aim of this study is to describe aggressiveness in the epilepsy population
      and to identify possible relationships between this type of behavior and clinical
      and sociodemographic variables. Aggressive responses were measured by the
      Aggression Questionnaire (AQ), a standardized and validated instrument, which was
      administered to 503 patients from nine Italian centers for the care of epilepsy.
      Aggressive behavior in patients with epilepsy was different from that in the
      normal Italian population. After adjustment for age and sex, when appropriate,
      the following variables significantly affected aggressiveness: presence of
      compromised intellectual functioning, psychiatric disturbances, disability
      status, number of medications, geographic distribution, education, chronologic
      age, and disease duration. Our study offers a starting point for further
      investigations aimed at better understanding the mechanisms connecting aggression
      and epilepsy.

PMID- 22958167
TI  - Conservation stories, conservation science, and the role of the intergovernmental
      platform on biodiversity and ecosystem services.

PMID- 22958169
TI  - Enantioselective hydrogenation of beta-ketophosphonates with chiral Ru(II)
      catalysts.
AB  - Highly effective asymmetric hydrogenation of beta-ketophosphonates in the
      presence of Ru-(S)-SunPhos as catalyst was realized; good to excellent
      enantioselectivities (up to 99.9% ee) and excellent diastereoselectivities (96:4)
      were obtained.

PMID- 22958170
TI  - DNA methylation/demethylation network expression in psychotic patients with a
      history of alcohol abuse.
AB  - BACKGROUND: Recent studies suggest that protracted and excessive alcohol use
      induces an epigenetic dysregulation in human and rodent brains. We recently
      reported that DNA methylation dynamics are altered in brains of psychotic (PS)
      patients, including schizophrenia and bipolar disorder patients. Because PS
      patients are often comorbid with chronic alcohol abuse, we examined whether the
      altered expression of multiple members of the DNA methylation/demethylation
      network observed in postmortem brains of PS patients was modified in PS patients
      with a history of chronic alcohol abuse. METHODS: DNA-methyltransferase-1 (DNMT1)
      mRNA-positive neurons were counted in situ in prefrontal cortex samples obtained
      from the Harvard Brain Tissue Resource Center, Belmont, MA. 10-11-translocation
      (TETs 1, 2, 3), apolipoprotein B editing complex enzyme (APOBEC-3C), growth and
      DNA-damage-inducible protein 45beta (GADD45beta), and methyl-binding domain
      protein-4 (MBD4) mRNAs were measured by quantitative real-time polymerase chain
      reaction in inferior parietal cortical lobule samples obtained from the Stanley
      Foundation Neuropathology Consortium, Bethesda, MD. RESULTS: We observed an
      increase in DNMT1 mRNA-positive neurons in PS patients compared with non-PS
      subjects. In addition, there was a pronounced decrease in APOBEC-3C and a
      pronounced increase in GADD45beta and TET1 mRNAs in PS patients with no history
      of alcohol abuse. In PS patients with a history of chronic alcohol abuse, the
      numbers of DNMT1-positive neurons were not increased significantly. Furthermore,
      the decrease in APOBEC-3C mRNA was less pronounced, while the increase in TET1
      mRNA had a tendency to be potentiated in those PS patients that were chronic
      alcohol abusers. GADD45beta and MBD4 mRNAs were not influenced by alcohol abuse.
      The effect of chronic alcohol abuse on DNA methylation/demethylation network
      enzymes cannot be attributed to confounding demographic variables or to the type
      and dose of medication used. CONCLUSIONS: Based on these results, we hypothesize
      that PS patients may abuse alcohol as a potential attempt at self-medication to
      normalize altered DNA methylation/demethylation network pathways. However, before
      accepting this conclusion, we need to study alterations in the DNA
      methylation/demethylation pathways and the DNA methylation dynamics in a
      substantial number of alcoholic PS and non-PS patients. Additional investigation
      may also be necessary to determine whether the altered DNA methylation dynamics
      are direct or the consequence of an indirect interaction of alcohol with the
      neuropathogenetic mechanisms underlying psychosis.

PMID- 22958172
TI  - Fruit and vegetable intake of primary school children: a study of school meals.
AB  - BACKGROUND: Despite an increasing focus on the nutritional content of school
      meals and initiatives such as the School Fruit and Vegetable Scheme, children are
      not meeting the recommended levels of fruit and vegetable consumption. The
      present study aimed to examine children's fruit and vegetable consumption in 15
      primary schools across the West Midlands region. METHODS: A total of 1296
      children, aged 4-11 years, were observed for five consecutive days and the
      consumption of all food items was measured using the weighed intake method.
      Differences in the mean intake of fruit, vegetables and foods high in fat and
      sugar between Key Stages 1 and 2 were determined. RESULTS: Two-thirds of the
      children in the present study did not consume any fruit at lunchtime and only 3%
      of children consumed at least one portion as part of their school meal. The
      proportion of children consuming some quantity of vegetable at lunchtime was more
      than double that consuming fruit. Children in Key Stage 1 consumed significantly
      more vegetables on average than children in Key Stage 2 (P <= 0.05); however, no
      significant differences were found for the consumption of fruit. CONCLUSIONS:
      Despite the introduction of food-based standards for school meal provision;
      children are not consuming adequate portions of fruit and vegetables at
      lunchtime. The importance of strategies used by catering staff to promote the
      consumption of fruit and vegetables should be harnessed to encourage children to
      taste fruit and vegetables provided. Further research is recommended to increase
      the evidence base on strategies aiming to promote fruit and vegetable consumption
      in children.

PMID- 22958171
TI  - General acid-base catalysis mediated by nucleobases in the hairpin ribozyme.
AB  - The catalytic mechanism by which the hairpin ribozyme accelerates cleavage or
      ligation of the phosphodiester backbone of RNA has been incompletely understood.
      There is experimental evidence for an important role for an adenine (A38) and a
      guanine (G8), and it has been proposed that these act in general acid-base
      catalysis. In this work we show that a large reduction in cleavage rate on
      substitution of A38 by purine (A38P) can be reversed by replacement of the 5'
      oxygen atom at the scissile phosphate by sulfur (5'-PS), which is a much better
      leaving group. This is consistent with A38 acting as the general acid in the
      unmodified ribozyme. The rate of cleavage of the 5'-PS substrate by the A38P
      ribozyme increases with pH log-linearly, indicative of a requirement for a
      deprotonated base with a relatively high pK(a). On substitution of G8 by
      diaminopurine, the 5'-PS substrate cleavage rate at first increases with pH and
      then remains at a plateau, exhibiting an apparent pK(a) consistent with this
      nucleotide acting in general base catalysis. Alternative explanations for the pH
      dependence of hairpin ribozyme reactivity are discussed, from which we conclude
      that general acid-base catalysis by A38 and G8 is the simplest and most probable
      explanation consistent with all the experimental data.

PMID- 22958173
TI  - Effects of silver nanoparticles in diatom Thalassiosira pseudonana and
      cyanobacterium Synechococcus sp.
AB  - The aim of the present study was to investigate the effect of silver
      nanoparticles (AgNP) of different sizes toward two primary producer aquatic
      species. Thalassiosira pseudonana and Synechococcus sp. have been selected as
      representative models for the lower trophic organisms in marine and freshwater
      habitats, respectively. Time-dependent cellular growth was measured upon exposure
      to both AgNP and silver nitrate (AgNO(3)). In addition, AgNP behavior in
      freshwater and marine waters has been followed by CPS disc centrifuge, in the
      time frame of AgNP exposure studies, and the kinetic release of silver from AgNP
      of different sizes was measured by dialysis and inductively coupled plasma mass
      spectrometry (ICP-MS). The combination and interpretation of all these data
      suggest that a shared effect of AgNP and released silver was responsible for the
      toxicity in both organisms. Furthermore, the toxic effects induced by AgNP
      exposure in the present study seem to result from a mixture of parameters
      including aggregated state, size of the AgNP, stability of the preparation, and
      speciation of the released silver.

PMID- 22958174
TI  - Editorial Comment from Dr Ishizuka to effect of intrathecal administration of E
      series prostaglandin 1 receptor antagonist in a cyclophosphamide-induced cystitis
      rat model.

PMID- 22958175
TI  - Association of dopamine-related gene alleles, smoking behavior and decline in
      FEV1 in subjects with COPD: findings from the lung health study.
AB  - Cigarette smoking is the major risk factor for chronic obstructive pulmonary
      disease (COPD). Specific dopamine related gene alleles have previously been found
      to be associated with smoking initiation, maintenance and cessation. We
      investigated the association between specific dopamine related gene alleles and
      both change in smoking behavior and lung function change over time in individuals
      with mild-to-moderate COPD. Subjects included a subset of participants in the
      Lung Health Study (LHS), a smoking intervention study in smokers with mild to
      moderate COPD. Smoking status was determined and lung function performed at
      baseline and annually for 5 years. In post-hoc analyses, we assessed the
      association of the dopamine receptor (DRD2) TaqI A1(+) allele (A1A1, A1A2
      genotypes) and A1(-) allele (A2A2 genotype), and the dopamine transporter (DAT)
      9R(+) allele (9R9R and 9R10R genotypes) and 9R(-) allele (10R10R genotype) with
      both changes in smoking status and lung function in a subset of LHS subjects. No
      significant associations were noted between variants in these genes and success
      in smoking cessation. However, in exploratory analyses that did not adjust for
      multiple comparisons, sustained male (but not female) quitters with the DRD2 A1(
      ) allele and/or the DAT 9R(+) allele showed an accelerated decline in FEV(1)
      similar to that of continuing smokers over 5 years after quitting smoking. These
      preliminary findings suggest that dopamine-related genes may play a role in the
      progression of COPD, at least in the subset of male ex-smokers whose disease
      continues to progress despite sustained quitting, and warrants additional
      confirmatory and mechanistic studies.

PMID- 22958176
TI  - Plasmablastic lymphoma of the elderly: a clinicopathological comparison with age
      related Epstein-Barr virus-associated B cell lymphoproliferative disorder.
AB  - AIMS: Plasmablastic lymphoma (PBL) is an aggressive lymphoma with a terminally
      differentiated B cell phenotype; half of patients with this disease have Epstein
      Barr virus (EBV) infection. The majority of PBL cases are associated with human
      immunodeficiency virus (HIV) infection, while the remaining HIV-negative cases
      were accompanied by other immunodeficiency conditions or immunosenescence in the
      elderly. METHODS AND RESULTS: To characterize HIV-negative PBL of the elderly
      (PBL-E), we compared the clinicopathological characteristics of 10 cases of PBL-E
      and 124 cases with age-related EBV-associated B cell lymphoproliferative disorder
      (AR-EBVLPD). The 10 PBL-E (eight men, two women; median age: 68 years) were
      associated with a more indolent clinical behaviour and a better overall survival
      than AR-EBVLPD. Extranodal involvement was higher in PBL-E (50%) than AR-EBVLPD;
      notably, the nasal cavity was affected most frequently in PBL-E (60%).
      Immunoglobulin heavy chain/(IGH)/MYC translocation was detected in half of the
      PBL-E cases. CONCLUSIONS: PBL-E shares some clinical features with AR-EBVLPD,
      such as HIV negativity, old age, and EBV infection, no known immunosuppressive
      condition but there are some differences such as a higher ratio of extranodal
      involvement and better prognosis. PBL-E is a newly recognized condition and
      should be distinguished from HIV-positive PBL, sharing features with AR-EBVLPD in
      particular, immunosenescence of the elderly.

PMID- 22958177
TI  - Spectrum of F8 gene mutations in haemophilia A patients from Slovenia.

PMID- 22958178
TI  - A healthcare management system for Turkey based on a service-oriented
      architecture.
AB  - The current Turkish healthcare management system has a structure that is
      extremely inordinate, cumbersome and inflexible. Furthermore, this structure has
      no common point of view and thus has no interoperability and responds slowly to
      innovations. The purpose of this study is to show that using which methods can
      the Turkish healthcare management system provide a structure that could be more
      modern, more flexible and more quick to respond to innovations and changes taking
      advantage of the benefits given by a service-oriented architecture (SOA). In this
      paper, the Turkish healthcare management system is chosen to be examined since
      Turkey is considered as one of the Third World countries and the information
      architecture of the existing healthcare management system of Turkey has not yet
      been configured with SOA, which is a contemporary innovative approach and should
      provide the base architecture of the new solution. The innovation of this study
      is the symbiosis of two main integration approaches, SOA and Health Level 7
      (HL7), for integrating divergent healthcare information systems. A model is
      developed which is based on SOA and enables obtaining a healthcare management
      system having the SSF standards (HSSP Service Specification Framework) developed
      by the framework of the HSSP (Healthcare Services Specification Project) under
      the leadership of HL7 and the Object Management Group. 

PMID- 22958179
TI  - Infantile hemangioma: treatment with short course systemic corticosteroid therapy
      as an alternative for propranolol.
AB  - Infantile hemangiomas (IHs) are increasingly being treated with propranolol or
      other beta-blockers, but before this therapeutic option was available, oral
      glucocorticosteroids (GCSs) were the criterion standard treatment and are still
      the alternative modality in problematic cases. Nevertheless, there is no standard
      treatment protocol for the dose and duration of GCSs. Long-term treatment with
      GCSs is associated with unwanted side effects such as growth suppression,
      behavioral changes, and reflux. Twenty-one children with troublesome IHs were
      treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided
      three times per day with varying duration and number of GCS courses. Two blinded
      investigators independently interpreted therapy results using the Hemangioma
      Activity Score (HAS). Side effects were determined according to reports in
      patient charts and parental questionnaires. The median duration of a short course
      of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5).
      The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with
      a good response (>50% reduction in HAS) in 62% and a favorable response (30-50%
      reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects.
      Persistent side effects did not occur. Intermittent short course, systemic, high
      dose GCS therapy is an effective and safe treatment modality for IH, with a
      substantially lower cumulative dose of GCSs compared to prolonged therapy and no
      major side effects. This treatment is an alternative in cases in which
      propranolol fails or is contraindicated.

PMID- 22958180
TI  - The ABCB6 mutation p.Arg192Trp is a recessive mutation causing the Lan- blood
      type.
AB  - BACKGROUND AND OBJECTIVE: The membrane transporter ABCB6 has recently been shown
      to carry the high-frequency red-blood-cell (RBC) antigen Lan. All the Lan-
      individuals genotyped so far have inherited two recessive null mutations in
      ABCB6. The finding of a family with the Lan- blood type occurring in two
      successive generations prompted this study. METHODS: Mutations in ABCB6 were
      searched by Sanger sequencing of exons and flanking intronic regions. Expression
      analysis of the Lan antigen was carried out by serology and flow cytometry. PCR
      RFLP genotyping and Western blot analysis were also applied. RESULTS: All the Lan
      members of this family were homozygous for c.574C>T, p.Arg192Trp in ABCB6 while
      the Lan+ members were heterozygous for this missense mutation encoded by the SNP
      rs149202834. Homozygosity for p.Arg192Trp was associated not only with absence of
      the Lan antigen, but also of the ABCB6 transporter in RBC membrane. The complete
      absence of Lan expression resulting from p.Arg192Trp homozygosity was confirmed
      by the subsequent identification of five unrelated Lan- individuals who were
      homozygous for this mutation and who developed an anti-Lan. We also provide
      evidence that three other single amino acid mutations in ABCB6 (c.826C >T,
      p.Arg276Trp; c.85_87delTTC, p.Phe29del; c.1762G >A, p.Gly588Ser) may also define
      ABCB6 null alleles. CONCLUSION: p.Arg192Trp is the first ABCB6 missense mutation
      causing the Lan- blood type and appears to be a relatively frequent cause of this
      rare blood type. Like the previously reported frameshift, nonsense and essential
      splice-site mutations in ABCB6, this missense mutation is recessive and defines
      an ABCB6 null allele. Other single amino acid mutations in ABCB6 may also cause
      the Lan- blood type.

PMID- 22958181
TI  - Associations of systemic diseases, smoking and contact lens wear with severity of
      dry eye.
AB  - PURPOSE: Systemic diseases, smoking, ocular surgeries and contact lens wear have
      been linked with dry eye but it is not known if these factors are also associated
      with severity of dry eye. A cross-sectional investigation was conducted on the
      effect of various systemic and ocular conditions with respect to the severity of
      dry eye in Asian patients. METHODS: Prospective recruitment of consecutive new
      referral patients from a dry eye clinic was performed. Medical history, dry eye
      symptoms and clinical assessment were coded in a standardised form and analysed.
      RESULTS: Out of 510 patients (25% men), mean +/- S.D. age 53.0 +/- 14.1 years, 25
      had previous diagnosis of rheumatoid arthritis, 30 had diabetic mellitus, 41 had
      thyroid disease, and 33 were current smokers; 23 and 41 patients had previous
      LASIK and cataract surgery respectively and 90 were current contact lenses
      wearers. A previous diagnosis of rheumatoid arthritis was associated with more
      severe superior corneal fluorescein staining (OR = 11.2, 95% CI 4.6-27.4).
      CONCLUSION: Generally, with the exception of rheumatoid arthritis, there were no
      associations between dry eye severity and systemic diseases, smoking, previous
      ocular surgeries and contact lens wear. Dry eye patients with rheumatoid
      arthritis tend to have more severe ocular surface damage in the superior cornea.

PMID- 22958182
TI  - Release and bioaccessibility of beta-carotene from fortified almond butter during
      in vitro digestion.
AB  - The objective of this study was to determine the release and bioaccessibility of
      beta-carotene from fortified almond butter using in vitro digestion models. Two
      types of fortifiers were investigated: beta-carotene oil (oil) and whey protein
      isolate (WPI)-alginate-chitosan capsules containing beta-carotene oil (capsule).
      Shaking water bath and Human Gastric Simulator (HGS) digestion models assessed
      the impact of gastric peristalsis on the release of beta-carotene.
      Bioaccessibility of beta-carotene was measured as percent recovered from the
      micelle fraction. There was greater release of beta-carotene from oil fortified
      almond butter in the HGS model (87.1%) due to peristalsis than the shaking water
      bath model (51.0%). More beta-carotene was released from capsule fortified almond
      butter during intestinal digestion. However, more beta-carotene was recovered
      from the micelle fraction of oil fortified almond butter. These results suggest
      that a WPI-alginate-chitosan capsule coating may inhibit the bioaccessibility of
      beta-carotene from fortified almond butter.

PMID- 22958183
TI  - Inhibition of microRNA-21 increases radiosensitivity of esophageal cancer cells
      through phosphatase and tensin homolog deleted on chromosome 10 activation.
AB  - The radioresistance of esophageal squamous cell carcinoma is a great obstacle to
      treatment. Although it has been demonstrated that microRNA-21 (miR-21) can act as
      an 'oncogene' in esophageal squamous cell carcinoma, its role in radioresistance
      remains unexplored. The aims of this study were to investigate the role of miR-21
      in esophageal squamous carcinoma cells' radioresistance and to identify the
      possible mechanism. The relatively radioresistant esophageal squamous cancer TE-1
      cells (TE-R60) was established by fractionated irradiation. By lentiviral
      transduction with miRZip-21, the miR-21 expression in TE-1 cells was stably
      downregulated, which was renamed as 'anti-miR-21 TE-1 cells.' The phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN) was knocked down in anti-miR-21 TE
      1 cells through short interfering RNA. The expression level of miR-21 and PTEN
      messenger RNA were measured by quantitative real-time reverse transcription
      polymerase chain reaction or reverse transcription polymerase chain reaction. The
      expression level of PTEN, phospho-Akt, and Akt protein were detected by Western
      blot. Clongenic assay was used to analyze the cells' radiosensitivity. miR-21 was
      overexpressed, and PTEN was suppressed in established radioresistant TE-R60 cells
      compared with the parent cells (1.3-fold and 70.83%). The inhibition of miR-21
      significantly increased the cells' radiosensitivity (P < 0.05) and the PTEN
      protein expression (2.3-fold) in TE-1 cells. In addition, phospho-Akt protein,
      downstream target of PTEN, reduced significantly in anti-miR-21 TE-1 cells.
      Knockdown of PTEN in anti-miR-21 TE-1 cells could abrogate the miR-21 inhibition
      induced radiosensitization (P < 0.05). Inhibition of miR-21 increased
      radiosensitivity of esophageal cancer TE-1 cells, and this effect was possibly
      through the activation of PTEN. Inhibition of miR-21 may form a novel therapeutic
      strategy to increase the radiosensitivity of esophageal cancer. 

PMID- 22958184
TI  - Atrial septostomy in patients with end-stage pulmonary hypertension. No more
      needles but wires, energy and close anatomical definition.
AB  - OBJECTIVES: To assess the usefulness of a new approach to atrial septal puncture
      and septostomy in patients with end-stage pulmonary hypertension. BACKGROUND:
      Atrial septostomy in end-stage pulmonary hypertension has high mortality and
      morbidity rates mainly due to trans-septal catheterization. New approaches to
      safety during this technical step are expected. METHODS: Twelve patients with end
      stage pulmonary arterial hypertension (5 males, 7 females, mean age 41, 9 +/- 12,
      0 years) underwent to balloon atrial septostomy. Intracardiac echography (ICE)
      was used to localize fossa ovalis while a radiofrequency wire was used to
      perforate the atrial septum. Then a septostomy was performed by progressive
      balloon dilatation of atrial septum. Septal perforation was successful at the
      first attempt in 4 patients and after 5 attempts in a single case, while Bas was
      successful in all. RESULTS: Pericardial effusion did not develop in any patient.
      Complications consisted in transient supraventricular tachyarrhythmia, transient
      cerebral ischemia and severe hypoxemia with ventricular tachycardia in 3 single
      patients. In-procedure death rate was 0%. Systemic cardiac output increased
      immediately, while systemic O2 saturation decreased significantly in all. Mean
      follow-up was 8, 2 +/- 3, 8 months. Mortality was 16.6% (2 patients). NYHA class
      improved in the rest of patients. Four patients (33.2%) underwent to pulmonary
      transplant successfully. CONCLUSIONS: This novel approach for trans-septal
      catheterization has shown very low rate of major complication during atrial
      septostomy in patients with end-stage pulmonary arterial hypertension.

PMID- 22958185
TI  - Present and future challenges in food analysis: foodomics.
AB  - The state-of-the-art of food analysis at the beginning of the 21st century is
      presented in this work, together with its major applications, current
      limitations, and present and foreseen challenges.

PMID- 22958186
TI  - Prognostic value of trisomy 8 as a single anomaly and the influence of additional
      cytogenetic aberrations in primary myelodysplastic syndromes.
AB  - Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS),
      however, little is known about the features of MDS with isolated trisomy 8 and
      the influence of additional cytogenetic aberrations. We determined the
      characteristics and prognostic factors of 72 patients with trisomy 8 as a single
      anomaly and analysed also the impact of other aberrations added to trisomy 8 in
      another 62 patients. According to our study, MDS with isolated trisomy 8 was more
      frequent in men, with more than one cytopenia in most patients (62%) and having
      about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet
      count and percentage bone marrow blasts had the strongest impact on overall
      survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one
      aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8
      + >=3) was 34.3, 40, 23.4 and 5.8 months, respectively (P < 0.001). Trisomy 8
      confers a poorer prognosis than a normal karyotype in MDS patients with >=5% bone
      marrow blasts. This study supports the view that MDS with isolated trisomy 8
      should be included in the intermediate cytogenetic risk group.

PMID- 22958187
TI  - Intergenotypic variation of endothelial dysfunction and inflammatory markers in
      eclampsia.
AB  - BACKGROUND: Cytokine imbalance and endothelial dysfunction are suggested to have
      a pivotal role in eclampsia. Pathophysiological processes are influenced by
      genetic factors and nitric oxide (NO) synthases seem to play important roles,
      although their role is still unclear. Endothelial NO synthase (eNOS) gene
      polymorphism may affect cytokine production. The aim of this study was to test
      the hypothesis that inflammatory cytokines impairs endothelium-dependent
      relaxation and NO production gets vitiated due to eNOs Glu298Asp gene
      polymorphism causing endothelial dysfunction in eclampsia. METHODS: This cross
      sectional study included 100 women with eclampsia and 100 healthy pregnant women.
      Their blood samples were analyzed for NO (indirectly), and inflammatory cytokines
      and eNOS (Glu298Asp) gene polymorphism were determined by DNA extraction,
      followed by restriction fragment length polymorphism. RESULTS: Decreased NO
      metabolites and increased cytokines (tumor necrosis factor-alpha; interleukin-2, 
      6; and interferon-gamma) levels were found in eclampsia (p < 0.001). Significant
      differences were found in genotype/allele distribution between the two groups.
      Occurrence of "T" allele frequency was found to be 0.27 among patients and 0.05
      among controls (CI = 95%, OR = 0.7-0.9, p < 0.001). Significant negative
      correlation was seen between NO and cytokines levels (tumor necrosis factor-alpha
      and interferon-gamma) in eclamptic women (p = 0.001). CONCLUSION: This study
      concluded that eclampsia is associated with decreased levels of NO and increased
      levels of circulating inflammatory cytokines, which might be contributed due to
      single-nucleotide polymorphism, pointing toward the role of endothelial and
      inflammatory components.

PMID- 22958188
TI  - Chemistry on Boranils: an entry to functionalized fluorescent dyes.
AB  - A Boranil fluorophore bearing a nitro-phenyl group has been selectively reduced
      to its anilino form and then successfully converted to amide, imine, urea, and
      thiourea derivatives which are fluorescent dyes. Its isolated isothiocyanate
      intermediate derivative was used in a model labeling experiment with Bovine Serum
      Albumin (BSA). The purified labeled-BSA exhibits strong luminescence (Phi(f) =
      47%) in a phosphate buffer at pH = 7.4.

PMID- 22958189
TI  - Dynamics and efficiency of hole transport in LNA:DNA hybrid diblock oligomers.
AB  - We report here the effect of replacing one or both of the purine or pyrimidine
      blocks of a diblock stilbene donor-acceptor capped hairpin with locked nucleic
      acid (LNA) bases on the dynamics and efficiency of hole transport. The structures
      of the DNA and LNA:DNA hybrids are tentatively assigned to B- or A-type
      structures on the basis of their circular dichroism spectra. Replacing the bases
      in either the A-block or the G-block of the diblock DNA hairpin with LNA bases
      results in a modest decrease in the base-to-base hopping rate constant and
      quantum yield for charge separation. Somewhat larger decreases are observed when
      all of the purine or pyrimidine bases are replaced by LNA bases.

PMID- 22958190
TI  - Vagus nerve stimulation elevates seizure threshold in the kindling model.
AB  - PURPOSE:   Vagus nerve stimulation (VNS) provides partial relief of medically
      refractory partial seizures in a subset of patients. The optimal pattern of
      stimulation and the mechanism of the antiseizure effects are uncertain.
      Establishing the efficacy of VNS in an animal model of epilepsy would provide an
      experimental preparation with which to address these questions. We sought to
      determine whether VNS exerted antiseizure effects in the kindling model of
      epilepsy. METHODS:   We implanted adult rats with bipolar stimulating electrodes
      in the right amygdala and VNS devices around the left vagus nerve. Following
      induction of kindling, electrographic seizure threshold (EST) was determined by
      quantifying the amygdala electrode current required to evoke a seizure. Once
      stable ESTs were established, VNS devices were programmed to deliver U.S. Food
      and Drug Administration (FDA)-approved, clinically used (standard) or an
      experimental (microburst) pattern of stimulation of variable intensity. VNS
      devices were programmed identically in control animals except that no current was
      delivered. EST was examined at 60 min and 1 week in the control and vagus nerve
      stimulated groups. KEY FINDINGS:   Significant reductions of EST values were
      detected in control animals when tested both 60 min and 1 week following device
      programming. Both clinically used and experimental patterns of VNS prevented the
      reduction of EST evident in control animals when tested either 60 min or 1 week
      after device programming. SIGNIFICANCE:   These findings establish an
      experimental preparation with which to elucidate the antiseizure mechanisms of
      VNS and to determine patterns of VNS most effective at elevating seizure
      threshold.

PMID- 22958191
TI  - To attend or not attend? A critical review of the factors impacting on initial
      appointment attendance from an approach-avoidance perspective.
AB  - BACKGROUND: A large proportion of initial therapy appointments are not attended.
      Whether this reflects service-user choice or an unmet need for therapy, non
      attendance can impact on patients, therapists, services and research evaluation.
      AIMS: To understand the complexities of this phenomenon, this paper reviews the
      mental health literature to gain further insight into how predictor variables can
      influence professional help-seeking decisions. METHODS: This review reveals a
      modest success at identifying specific demographic and psychological factors, yet
      methodological issues surrounding data collection techniques have often led to
      contradictory and inconclusive findings. CONCLUSIONS: This paper examines the
      possibility that approach-avoidance conflict [Kushner, M.G. & Sher, K.J. (1989,
      1991). Fear of psychological treatment and its relation to mental health service
      avoidance. Professional Psychology: Research and Practice, 20, 251-257; The
      relation of treatment fearfulness and psychological service utilization: An
      overview. Professional Psychology: Research and practice, 22, 196-203] could
      explain the contradictions in the literature because, in this model, different
      factors involved in driving engagement versus avoidance become more salient
      depending on a dynamic interplay of timing, the individual and their service
      context. The core principles behind this approach-avoidance conceptualisation are
      explained and further avenues for research are identified.

PMID- 22958192
TI  - Association between myopia and diabetic retinopathy: a review of observational
      findings and potential mechanisms.
AB  - A protective, but inconsistent association between myopia and a decreased risk of
      diabetic retinopathy (DR) has been suggested in several studies. However, it is
      unclear whether the structural, or the refractive components of myopia; or both,
      is the main contributor to this protective relationship. This paper provides a
      comprehensive review of existing evidence on the association between myopia, and
      its structural (axial length [AL], anterior chamber depth [ACD]) and refractive
      (lens biometry and corneal curvature [CC]) components, with DR. 11 studies
      consisting of 7230 subjects from 1960 to April 2012, were reviewed. A longer AL
      was the only variable associated with a lower risk and severity of DR. Therefore,
      the available evidence suggests that AL is the main contributor to the protective
      influence of myopia on DR observed in earlier studies. Further investigations are
      now needed to determine the mechanisms by which AL protects against DR.

PMID- 22958193
TI  - The first liver transplantation from infant donors after cardiac death in China.

PMID- 22958195
TI  - Home enteral tube feeding in children with inherited metabolic disorders: a
      review of long-term carer knowledge and technique.
AB  - BACKGROUND: Home enteral tube feeding (HETF) is commonly used in children with
      inherited metabolic disorders (IMD). It is unclear how caregiver knowledge and
      their safety in using tube feeding techniques changes over time. METHODS:
      Caregivers of children with IMD on HETF from one UK IMD centre had annual
      interviews over 3 years using a structured questionnaire and observation to
      assess HETF knowledge and safety techniques. RESULTS: Thirty-two caregivers of
      IMD children (median age 5.3 years; range 0.3-13.6 years) were studied. Seventy
      eight percent (n = 25) of subjects had been on HETF for >5 years. Over 3 years,
      many caregivers' HETF techniques deteriorated: accurate feed ingredient
      measurement decreased from 36% to 11%; correct flushing of tubes decreased from
      56% to 44%; checking tube position as recommended decreased from 72% to 56%; and
      correct hand washing decreased from 38% to 25%. Despite improvements, knowledge
      of some aspects remained poorly understood: dangers of incorrect tube placement
      increased from 41% to 56%; correct position for night feeding increased from 38%
      to 56%; and feed ingredient storage decreased from 87% to 38%. CONCLUSIONS: The
      HETF techniques of caregivers of children with IMD declined over time. Caregivers
      need to understand that HETF, particularly in IMD, is a serious procedure
      associated with life-threatening risks. Poor HETF practices may cause feed
      contamination, incorrect feed concentration, feed intolerance, aspiration,
      peritonitis and even metabolic decompensation. HETF skills should be reassessed
      annually, with compulsory retraining if basic 'core' HETF competencies are not
      demonstrated.

PMID- 22958194
TI  - F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics
      Study (HIGS) Combined Cohort.
AB  - Ancestral background, specifically African descent, confers higher risk for
      development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It
      has been suggested that differences in the distribution of FVIII gene (F8)
      haplotypes, and mismatch between endogenous F8 haplotypes and those comprising
      products used for treatment could contribute to risk. Data from the Hemophilia
      Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the
      association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and
      inhibitor risk among individuals of genetically determined African descent. Other
      variables known to affect inhibitor risk including type of F8 mutation and human
      leucocyte antigen (HLA) were included in the analysis. A second research question
      regarding risk related to mismatch in endogenous F8 haplotype and recombinant
      FVIII products used for treatment was addressed. Haplotype 3 was associated with
      higher inhibitor risk among those genetically identified (N = 49) as of African
      ancestry, but the association did not remain significant after adjustment for F8
      mutation type and the HLA variables. Among subjects of all racial ancestries
      enrolled in HIGS who reported early use of recombinant products (N = 223),
      mismatch in endogenous haplotype and the FVIII proteins constituting the products
      used did not confer greater risk for inhibitor development. Haplotype 3 was not
      an independent predictor of inhibitor risk. Furthermore, our findings did not
      support a higher risk of inhibitors in the presence of a haplotype mismatch
      between the FVIII molecule infused and that of the individual.

PMID- 22958196
TI  - The duration of sulfonylurea treatment is associated with beta-cell dysfunction
      in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: This study investigated the incidence of beta-cell dysfunction and
      the clinical and biochemical factors affecting that in patients with type 2
      diabetes having more than 3 years of follow-up. SUBJECTS AND METHODS: beta-Cell
      dysfunction was assessed by measuring changes in the fasting serum C-peptide
      concentrations. Patients were classified into two groups: cases showing a
      decreased (Group D) or an unchanged or increased (Group I) C-peptide
      concentration from the baseline. RESULTS: Of the 504 patients included in this
      study, 259 (51%) showed decreased C-peptide concentrations, of whom 20% showed a
      decrease of >=50%. Most patients, however, had a final C-peptide concentration of
      >=1 ng/mL, with only 18 (4%) individuals having a level <0.6 ng/mL. Patients in
      Group D had a longer duration of diabetes, higher initial hemoglobin A1c
      concentration, and longer treatment durations with sulfonylurea and insulin
      compared with Group I. After adjusting for diabetes duration and C-peptide follow
      up period, the duration of sulfonylurea treatment was found to be the only factor
      independently associated with decreases in the C-peptide concentration.
      CONCLUSIONS: Although beta-cell function deteriorates over time in patients with
      type 2 diabetes, these cases mainly have fasting serum C-peptide concentrations
      of >=1 ng/mL. A longer treatment duration with sulfonylurea is associated with a
      more rapid decline in the C-peptide concentration.

PMID- 22958197
TI  - Therapeutic strategies for prevention of postoperative recurrence in patients
      with Crohn's disease.

PMID- 22958198
TI  - Improving diagnostic accuracy using agent-based distributed data mining system.
AB  - The use of data mining techniques to improve the diagnostic system accuracy is
      investigated in this paper. The data mining algorithms aim to discover patterns
      and extract useful knowledge from facts recorded in databases. Generally, the
      expert systems are constructed for automating diagnostic procedures. The learning
      component uses the data mining algorithms to extract the expert system rules from
      the database automatically. Learning algorithms can assist the clinicians in
      extracting knowledge automatically. As the number and variety of data sources is
      dramatically increasing, another way to acquire knowledge from databases is to
      apply various data mining algorithms that extract knowledge from data. As data
      sets are inherently distributed, the distributed system uses agents to transport
      the trained classifiers and uses meta learning to combine the knowledge.
      Commonsense reasoning is also used in association with distributed data mining to
      obtain better results. Combining human expert knowledge and data mining knowledge
      improves the performance of the diagnostic system. This work suggests a framework
      of combining the human knowledge and knowledge gained by better data mining
      algorithms on a renal and gallstone data set. 

PMID- 22958199
TI  - Role of orthophosphate as a corrosion inhibitor in chloraminated solutions
      containing tetravalent lead corrosion product PbO2.
AB  - Addition of orthophosphate has been commonly employed to suppress lead levels in
      drinking water. Its detailed mechanism and time required for it to become
      effective, however, have not been fully elucidated. In this study, we
      investigated the mechanistic role of orthophosphate as a corrosion inhibitor in
      controlling lead release from tetravalent lead corrosion product PbO(2) in
      chloraminated solutions, a system representing distribution networks experiencing
      disinfectant changeover from free chlorine to monochloramine. In all experiments
      with orthophosphate addition of at least 1 mg/L as P, peaking of soluble Pb(II)
      concentration within the first 24 h was observed before lead concentrations
      decreased and stabilized at levels lower than 15 MUg/L. The variation of soluble
      Pb(II) concentration could be attributed to the dynamics between the rate of
      PbO(2) reductive dissolution, primarily induced by monochloramine decomposition,
      and that of chloropyromorphite (Pb(5)(PO(4))(3)Cl) precipitation, which did not
      occur until a critical supersaturation ratio of about 2.36 was reached in the
      solution. Our findings provide insights to how orthophosphate reduces lead levels
      under drinking water conditions and highlight the potential risk of short-term
      elevated lead concentrations. Intensive monitoring following the disinfectant
      changeover may be required to determine the overall lead exposure when using
      orthophosphate as a corrosion inhibitor.

PMID- 22958200
TI  - Evaluation and optimization of discrete state models of protein folding.
AB  - The space accessed by a folding macromolecule is vast, and how to best project
      computer simulations of protein folding trajectories into an interpretable
      sequence of discrete states is an open research problem. There are numerous
      alternative ways of associating individual configurations into collective states,
      and in deciding on the number of such clustered states there is a trade-off
      between human interpretability (smaller number of states) and accuracy of
      representation (larger number of states). Here we introduce a trajectory
      likelihood measure for assessing alternative discrete state models of protein
      folding. We find that widely used rmsd-based clustering methods require large
      numbers of initial states and a second agglomeration step based on kinetic
      connectivity to produce models with high predictive power; this is the approach
      taken in elegant recent work with Markov State Models of protein folding. In
      contrast, we find that grouping of states based on secondary structure pairings
      or contact maps, when refined with K-means clustering, yields higher likelihood
      models with many fewer states. Using the most predictive contact map
      representation to study the folding transitions of the WW domain in very long
      molecular dynamics simulations, we identify new states and transitions. The
      methods should be generally useful for investigating the structural transitions
      in protein folding simulations for larger proteins.

PMID- 22958201
TI  - Poorly differentiated synovial sarcoma of the sphenoid sinus: report of the first
      case and review of synovial sarcomas of the sinonasal tract.

PMID- 22958202
TI  - Pharmacodynamic effects of the oral glucokinase activator AZD6370 after single
      doses in healthy volunteers assessed with euglycaemic clamp.
AB  - AIMS: This study evaluated the safety, tolerability, pharmacokinetics and
      pharmacodynamic effects of the glucokinase activator (GKA) AZD6370 in non
      diabetic subjects, using the euglycaemic clamp to avoid the risk of
      hypoglycaemia. METHODS: Oral single ascending doses of AZD6370 10-650 mg or
      subcutaneous short-acting insulin 4 or 12 U were given to healthy fasting
      subjects. AZD6370 safety, tolerability and pharmacokinetics were assessed.
      Pharmacodynamic effects on serum (S)-insulin and glucose infusion rate (GIR) were
      investigated with euglycaemic clamp. AZD6370 10-20 mg was also assessed when
      taken with food without euglycaemic clamp. RESULTS: AZD6370 was well tolerated
      and no safety concerns were raised. AZD6370 was rapidly absorbed and eliminated,
      and plasma concentration was proportional to dose. Both S-insulin and GIR
      increased following AZD6370 administration. The observed increase in GIR
      correlated with increasing AZD6370 area under the plasma concentration vs. time
      curve, demonstrating a dose-concentration-dependent pharmacodynamic effect.
      AZD6370 at doses of 50 and 80 mg had similar effects to short-acting insulin 4 U
      on peripheral S-insulin levels but greater effects on GIR, suggesting an effect
      beyond the increase of peripheral S-insulin levels at lower doses. In the food
      interaction part of the study, performed without euglycaemic clamp, dose
      escalation was stopped at a low dose (20 mg) because of hypoglycaemia.
      CONCLUSION: The euglycaemic clamp was successfully used to avoid hypoglycaemia
      and to demonstrate pharmacodynamic effects, that is, markedly increased insulin
      secretion and glucose utilisation, following administration of AZD6370 in healthy
      fasting subjects. In addition to the effect on pancreatic insulin secretion, the
      data support an extra-pancreatic (hepatic) component of GKA action.

PMID- 22958203
TI  - Influence of fermentation with Hanseniaspora sp. yeast on the volatile profile of
      fermented apple.
AB  - This study aims to evaluate the aromatic profile of fermented apple, obtained by
      the action of strains of  Hanseniaspora uvarum  and  Hanseniaspora guilliermondii
      using two methods of analysis: static headspace and solid phase microextraction
      (SPME). The results obtained confirm that the strains of the Hanseniaspora genus
      contributed positively to the aroma profile of fermented apple, producing
      considerable amounts of esters and higher alcohols. In comparing the methods of
      analysis of aromatic compounds using headspace and SPME, it was verified that by
      using the headspace method it was possible to capture amounts that were up to 16
      times greater than the value of the volatile compounds obtained by SPME. However,
      when using SPME, 5 times more compounds were obtained than when using headspace.
      Even so, in the conditions of this study it was noted that headspace was more
      efficient in the extraction of the aromatics of fermented apple when taking into
      consideration the cost effectiveness of both methods.

PMID- 22958204
TI  - Endovascular repair of traumatic aortic injury: a novel arena in interventional
      cardiology.
AB  - OBJECTIVE: To assess the feasibility of endovascular repair of traumatic aortic
      injuries performed by interventional cardiologists in collaboration with
      cardiothoracic surgeons. BACKGROUND: Traumatic aortic injury (TAI) represents a
      significant cause of mortality in trauma patients. Endovascular techniques have
      recently come into play for the management of TAI and are usually performed by a
      multidisciplinary team consisting of a thoracic or vascular surgeon and/or
      interventional radiology. With extensive expertise in catheter-based
      interventions, interventional cardiologists may have a pivotal role in this
      important procedure. METHODS: From January 2009 to July 2011, we reviewed the TAI
      endovascular repair outcomes performed by a team of interventional cardiologists
      in collaboration with cardiothoracic surgery at our institution. The charts of
      these patients were reviewed to collect desired data, which included
      preoperative, procedural, and follow-up details. RESULTS: Twenty patients were
      identified in our series. Most of these patients developed TAI from motor vehicle
      accidents. Technical success for endovascular repair of TAI was achieved in all
      patients. Two patients developed endoleak, of which one patient required
      subsequent open repair. Two patients expired in the hospital from coexistent
      injuries. CONCLUSIONS: Our series of endovascular repair for TAI performed by
      interventional cardiologists with the collaboration of cardiothoracic surgeons
      showed excellent outcomes. Our experience may give further insight in the
      collaborative role of interventional cardiology and cardiothoracic surgery for
      endovascular repair of TAI.

PMID- 22958205
TI  - Comment on "Hypersensitive luminiscence of Eu3+ in dimethyl sulfoxide as a new
      probing for water measurement".

PMID- 22958207
TI  - Expansion of enzymatic Friedel-Crafts alkylation on indoles: acceptance of
      unnatural beta-unsaturated allyl diphospates by dimethylallyl-tryptophan
      synthases.
AB  - Prenyltransferases of the dimethylallyl-tryptophan synthase (DMATS) superfamily
      catalyze Friedel-Crafts alkylation with high flexibility for aromatic substrates,
      but the high specificity for dimethylallyl diphosphate (DMAPP) prohibits their
      application as biocatalysts. We demonstrate here that at least one methyl group
      in DMAPP can be deleted or shifted to the delta-position. For acceptance by some
      DMATS enzymes, however, a double bond must be situated at the beta-position.
      Furthermore, the alkylation position of an analogue can differ from that of
      DMAPP.

PMID- 22958206
TI  - Increased age of transformed mouse neural progenitor/stem cells recapitulates age
      dependent clinical features of human glioma malignancy.
AB  - Increasing age is the most robust predictor of greater malignancy and treatment
      resistance in human gliomas. However, the adverse association of clinical course
      with aging is rarely considered in animal glioma models, impeding delineation of
      the relative importance of organismal versus progenitor cell aging in the genesis
      of glioma malignancy. To address this limitation, we implanted transformed neural
      stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3- and
      18-month-old mice into 3- and 20-month host animals. Transplantation with
      progenitors from older animals resulted in significantly shorter (P <= 0.0001)
      median survival in both 3-month (37.5 vs. 83 days) and 20-month (38 vs. 67 days)
      hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host
      animal age accounted for greater malignancy. Subsequent analyses revealed that
      increased invasiveness, genomic instability, resistance to therapeutic agents,
      and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater
      tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1
      promoter reporter activity and hypoxia response gene (HRG) expression, mirrors
      the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed
      by analysis of gene expression databases, suggesting that differential response
      to hypoxic stress may underlie age-dependent differences in invasion, genomic
      instability, and treatment resistance. Our study provides strong evidence that
      progenitor cell aging is responsible for promoting the hallmarks of age-dependent
      glioma malignancy and that consideration of progenitor aging will facilitate
      development of physiologically and clinically relevant animal models of human
      gliomas.

PMID- 22958208
TI  - Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell
      differentiation and NRSF/rest activity.
AB  - Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal
      function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan,
      catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2)
      have been identified, with TPH2 almost exclusively expressed in the brain.
      Following TPH2 discovery, it was reported that polymorphisms of both gene and non
      coding regions are associated with a spectrum of psychiatric disorders. Thus,
      insights into the mechanisms that specifically regulate TPH2 expression and its
      modulation by exogenous stimuli may represent a new therapeutic approach to
      modify serotonergic neurotransmission. To this aim, a CNS-originated cell line
      expressing TPH2 endogenously represents a valid model system. In this study, we
      report that TPH2 transcript and protein are modulated by neuronal differentiation
      in the cell line A1 mes-c-myc (A1). Moreover, we show luciferase activity driven
      by the human TPH2 promoter region and demonstrate that upon mutation of the
      NRSF/REST responsive element, the promoter activity strongly increases with cell
      differentiation. Our data suggest that A1 cells could represent a model system,
      allowing an insight into the mechanisms of regulation of TPH2 and to identify
      novel therapeutic targets in the development of drugs for the management of
      psychiatric disorders.

PMID- 22958209
TI  - Instructed extinction differentially affects the emotional and cognitive
      expression of associative fear memory.
AB  - Instructed extinction after fear conditioning is relatively effective in
      attenuating electrodermal responding. Testing the single-process account of fear
      learning, we examined whether this manipulation similarly affects the startle
      response. Skin conductance responses (SCRs), startle responses, and online
      unconditioned stimulus (US) expectancy ratings were measured during fear
      acquisition (Day 1), extinction, and reinstatement (Day 2). Before extinction
      onset, half of the subjects were instructed that the conditioned stimulus would
      not be followed by the US (Instructed Extinction) whereas the other subjects were
      not instructed (Normal Extinction). This simple instruction completely abolished
      both differential SCR and US expectancy ratings, but not the startle fear
      response. Although the manipulation facilitated extinction learning, it did not
      prevent the recovery of the startle response. The present findings are better
      explained by a dual- rather than a single-process account of fear learning.

PMID- 22958210
TI  - A comparison of in-air and in-saline focimeter measurement of the back vertex
      power of spherical soft contact lenses.
AB  - PURPOSE: To compare the repeatability and validity of measurements of the back
      vertex power (BVP) of spherical soft contact lenses made in-air using the method
      specified in the International Standard (ISO 18369-3:2006) with the corresponding
      values when BVP was calculated from measurements made using a wet cell and
      focimeter method that is not approved by this Standard. METHODS: The BVP of 20
      hydrogel and 20 silicone hydrogel lenses, with labelled powers ranging from +8.00
      to -12.00 D, were measured with a focimeter by two operators on two occasions in
      air in accordance with the relevant International Standard. Equivalent sets of
      measurements were made with the lenses immersed in-saline within a wet cell and
      their BVPs in-air were calculated. The validity of each method was assessed by
      comparing their results with an instrument that used the Hartmann method.
      RESULTS: The reliability results were generally a little better for the in-saline
      measurements than for the in-air measurements, although all reliability data
      demonstrated absolute values of mean errors (inter-operator and inter-session)
      that were <0.05 D for hydrogel lenses and <0.07 D for silicone hydrogel lenses.
      The in-air 95% confidence intervals were <0.45 D and <0.40 D for hydrogel and
      silicone hydrogel lenses, respectively and in-saline <0.39 and <0.31 D for
      hydrogel and silicone hydrogel lenses, respectively. The validity data revealed a
      relationship between measurement error and BVP for the in-air data (the focimeter
      overestimates the power of high plus and high minus lenses compared with the
      Hartmann instrument) and possibly a more complex relationship for the in-saline
      data. The 95% limits of agreement indicate better agreement for the in-saline
      validity data (-0.55 to +0.48 D for hydrogel lenses and -0.42 to +0.54 D for
      silicone hydrogel lenses) than those obtained in-air (-0.64 to +0.68 D for
      hydrogel lenses and -0.57 to +0.44 D for silicone hydrogel lenses). CONCLUSIONS:
      Using equipment readily available in a clinical setting, the wet cell method of
      measurement of the BVP of spherical soft contact lenses has been shown to provide
      results for reliability and validity that were at least as good as those obtained
      with the in-air method approved by the International Standard.

PMID- 22958211
TI  - Guideline-based development of quality indicators for hypertensive diseases in
      pregnancy.
AB  - OBJECTIVE: Hypertensive disorders in pregnancy are one of the main causes of
      maternal morbidity and mortality. Internationally, several organizations have
      developed clinical guidelines to assist professionals and to supply patients with
      the best possible care. To improve the care for this group of patients, insight
      into the application of clinical guidelines in daily practise is needed. Valid
      quality indicators are necessary to estimate actual guideline adherence. In this
      study, we developed a set of valid guideline-based quality indicators for
      hypertensive diseases in pregnancy. METHODS: A systematic RAND-modified Delphi
      method was used to develop a set of quality indicators on the basis of evidence
      based guidelines and literature on hypertension and pregnancy. Experts' opinions
      were used to select the indicators regarding specific criteria such as efficacy,
      level of health gain, and potential for care improvement. RESULTS: A
      representative set of 14 quality indicators was selected from 48 initial
      guideline recommendations. Indicators concerned both professional performance and
      organization of care for patients with hypertension in pregnancy. CONCLUSIONS:
      This study describes the systematic, stepwise method used to develop quality
      indicators that can be used to monitor care for hypertensive diseases in
      pregnancy.

PMID- 22958212
TI  - Seasonality of staphylococcal infections.
AB  - Characterization of seasonal variation of Staphylococcus aureus is important in
      understanding the epidemiology of, and designing preventive strategies against
      this highly virulent and ever-evolving pathogen. In this review, we summarize the
      findings of epidemiological studies that have evaluated seasonality in S. aureus
      colonization and infection. Although most studies published to date are
      methodologically weak, some seasonal variation in the occurrence of S. aureus
      infection appears to exist, particularly an association of warm-weather months
      with S. aureus skin and soft-tissue infections. We highlight the limitations of
      the published literature, and provide suggestions for future studies on this
      topic.

PMID- 22958213
TI  - Deviations in influenza seasonality: odd coincidence or obscure consequence?
AB  - In temperate regions, influenza typically arrives with the onset of colder
      weather. Seasonal waves travel over large spaces covering many climatic zones in
      a relatively short period of time. The precise mechanism for this striking
      seasonal pattern is still not well understood, and the interplay of factors that
      influence the spread of infection and the emergence of new strains is largely
      unknown. The study of influenza seasonality has been fraught with problems. One
      of these is the ever-shifting description of illness resulting from influenza and
      the use of both the historical definitions and new definitions based on actual
      isolation of the virus. The compilation of records describing influenza
      oscillations on a local and global scale is massive, but the value of these data
      is a function of the definitions used. In this review, we argue that observations
      of both seasonality and deviation from the expected pattern stem from the nature
      of this disease. Heterogeneity in seasonal patterns may arise from differences in
      the behaviour of specific strains, the emergence of a novel strain, or cross
      protection from previously observed strains. Most likely, the seasonal patterns
      emerge from interactions of individual factors behaving as coupled resonators. We
      emphasize that both seasonality and deviations from it may merely be reflections
      of our inability to disentangle signal from noise, because of ambiguity in
      measurement and/or terminology. We conclude the review with suggestions for new
      promising and realistic directions with tangible consequences for the modelling
      of complex influenza dynamics in order to effectively control infection.

PMID- 22958215
TI  - Treatment of common and plane warts in children with topical viable Bacillus
      Calmette-Guerin.
AB  - Treatment of verrucae in children is difficult and may be painful using
      traditional methods, especially if they are multiple or on the face. The
      objective of the current study was to evaluate the efficacy and safety of topical
      application of viable Bacillus Calmette-Guerin (BCG) in a paste formula as a new
      immunotherapeutic modality in the treatment of common and plane warts in
      children. The present study included 80 children with common and plane warts at
      different sites on the body. They were divided into two groups. Group A (40
      patients) received topical viable BCG and group B (40 patients) received topical
      saline as control. All patients and controls had received a previous vaccination
      of BCG. BCG was applied once weekly for six consecutive weeks. Patients who had
      partial or no response received another course of treatment for another 6 weeks.
      Follow-up was at 6 months to detect any recurrences. A highly significant
      difference was found between the therapeutic response of common and plane warts
      to BCG and saline (placebo) (p < 0.001). Complete response was achieved in 65% of
      children with common warts and 45% of patients with plane warts. No response was
      detected in the control group. No recurrences or side effects were observed in
      the BCG group. Topical immunotherapeutic BCG is a new, effective, safe treatment
      option for children with common and plane warts.

PMID- 22958216
TI  - Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by
      modulating lipid metabolism.
AB  - BACKGROUND: Vitamin D has been reported to be reversely associated with type 2
      diabetes and metabolic syndrome and is involved in modulation of lipid
      metabolism. The purpose of the present study was to determine whether 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2) D(3) ) has a protective effect on high fat
      diet (HFD)-induced hepatic steatosis in rats and to elucidate its underlying
      molecular mechanisms. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were
      fed with normal fat diet, HFD or HFD with intraperitoneal injection of 1, 2.5 and
      5 MUg/kg 1,25(OH)(2) D(3) , respectively, each 2 days for 8 weeks. Serum lipid
      profile and liver triglyceride were determined. Hepatic histology was examined by
      haematoxylin/eosin (H&E) and Oil Red O stainings. Hepatic gene expression
      involved in lipogenesis and lipid oxidation was analysed by quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The administration of
      1,25(OH)(2) D(3) prevented HFD-induced body weight gain and reduced liver weight.
      1,25(OH)(2) D(3) attenuated hepatic steatosis in a dose-dependent manner along
      with improved serum lipid profile. Furthermore, 1,25(OH)(2) D(3) downregulated
      mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c) and
      its target genes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)
      involved in lipogenesis. Peroxisome proliferator-activated receptor alpha
      (PPARalpha) and its target gene carnitine palmitoyltransferase-1 (CPT-1) involved
      in hepatic fatty acid (FA) oxidation were upregulated by 1,25(OH)(2) D(3) .
      CONCLUSIONS: These results suggest that the preventing effect of 1,25(OH)(2) D(3)
      against HFD-induced hepatic steatosis is related to the inhibition of lipogenesis
      and the promotion of FA oxidation in rat liver.

PMID- 22958217
TI  - Communication gaps for solid organ transplant-transmitted infections among
      infectious disease physicians: an Emerging Infections Network survey.
AB  - Infectious disease (ID) physicians were surveyed concerning knowledge and
      management of potential transplant-transmitted infections (TTIs). On the basis of
      cumulative responses to 4 questions that assessed solid organ transplant-related
      clinical exposures and experience, respondents were divided into 3 groups: most,
      some, or little transplant experience. Rapid access to donor data was identified
      as the most important factor when evaluating a potential TTI. Despite varying
      experience in transplant infections, ID physicians are frequently asked for
      opinions regarding donor suitability and TTI management. Improved ID physician
      access to donor information and educational resources will allow more optimal
      management of potential TTIs.

PMID- 22958218
TI  - Pulse gas chromatographic study of adsorption of substituted aromatics and
      heterocyclic molecules on MIL-47 at zero coverage.
AB  - The low coverage adsorptive properties of the MIL-47 metal organic framework
      toward aromatic and heterocyclic molecules are reported in this paper. The effect
      of molecular functionality and size on Henry adsorption constants and adsorption
      enthalpies of alkyl and heteroatom functionalized benzene derivates and
      heterocyclic molecules was studied using pulse gas chromatography. By means of
      statistical analysis, experimental data was analyzed and modeled using principal
      component analysis and partial least-squares regression. Structure-property
      relationships were established, revealing and confirming several trends. Among
      the molecular properties governing the adsorption process, vapor pressure, mean
      polarizability, and dipole moment play a determining role.

PMID- 22958219
TI  - Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene
      and its potential tumor suppressive role in pancreatic carcinogenesis.
AB  - BACKGROUND: We have recently identified HOP hoemobox (HOPX) as a tumor suppressor
      gene candidate, characterized by tumor-specific promoter DNA hypermethylation in
      human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In
      this current study, we for the first time examined methylation level of HOPX and
      tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical
      features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and
      immunohistochemistry was added. We also examined its functional relevance in
      phenotype assays such as soft agar, proliferation, invasion, and cell cycle
      analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the
      corresponding normal pancreas tissues, and its uniqueness was robust to
      discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly,
      HOPX was increased in expression in tumor tissues, and immunohistochemistry
      revealed its predominant expression in the Langerhans islet cells, where HOPX was
      reduced in expression for PC cells with promoter hypermethylation. HOPX
      transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor
      forming and invasive ability. CONCLUSION: Defective expression of HOPX which is
      consistent with promoter DNA hypermethylation may explain aggressive phenotype of
      pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in
      turn uniquely contribute to pancreatic carcinogenesis.

PMID- 22958220
TI  - Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial
      infarction in isolated rat hearts.
AB  - Recent studies have shown that stromal cell derived factor-1 (SDF-1), first known
      as a cytokine involved in recruiting stem cells into injured organs, confers
      myocardial protection in myocardial infarction, which is not dependent on stem
      cell recruitment but related with modulation of ischemia-reperfusion (I/R)
      injury. However, the effect of SDF has been studied only in a preischemic
      exposure model, which is not clinically relevant if SDF is to be used as a
      therapeutic agent. Our study was aimed at evaluating whether or not SDF-1 confers
      cardioprotection during the reperfusion period. Hearts from SD rats were isolated
      and perfused with the Langendorff system. Proximal left coronary artery ligation,
      reperfusion, and SDF perfusion in KH buffer was done according to study protocol.
      Area of necrosis (AN) relative to area at risk (AR) was the primary endpoint of
      the study. Significant reduction of AN/AR by SDF in an almost dose-dependent
      manner was noted during both the preischemic exposure and reperfusion periods. In
      particular, infusion of a high concentration of SDF (25 nM/L) resulted in a
      dramatic reduction of infarct size, which was greater than that achieved with
      ischemic pre- or postconditioning. SDF perfusion during reperfusion was
      associated with a similar significant reduction of infarct size as preischemic
      SDF exposure. Further studies are warranted to assess the potential of SDF as a
      therapeutic agent for reducing I/R injury in clinical practice.

PMID- 22958221
TI  - Eculizumab for atypical hemolytic uremic syndrome recurrence in renal
      transplantation.
AB  - Eculizumab (anti-C5) has been sporadically reported as an efficient therapy for
      atypical hemolytic uremic syndrome (aHUS). However, the lack of series precludes
      any firm conclusion about the optimal use of anti-C5 for preventing or treating
      aHUS posttransplant aHUS recurrence. We thoroughly studied 22 renal transplant
      recipients with aHUS who received off-label therapy with anti-C5, including 12
      cases, which have not been reported yet. Nine patients, all carrying a complement
      genetic abnormality associated with a high risk of aHUS recurrence, received
      prophylactic anti-C5 therapy to prevent posttransplant recurrence. Eight of them
      had a successful recurrence-free posttransplant course and achieved a
      satisfactory graft function, while the remaining patient experienced early
      arterial thrombosis of the graft. Thirteen renal transplant recipients were given
      anti-C5 for posttransplant aHUS recurrence. A complete reversal of aHUS activity
      was obtained in all of them. Importantly, the delay of anti-C5 initiation after
      the onset of the aHUS episode inversely correlated with the degree of renal
      function improvement. Three patients in whom anti-C5 was subsequently stopped
      experienced a relapse. Altogether these data suggest that long-term eculizumab is
      highly effective for preventing and treating posttransplant aHUS recurrence. Our
      study also indicates that anti-C5 should be promptly started if a recurrence
      occurs.

PMID- 22958223
TI  - Boundaries and e-health implementation in health and social care.
AB  - BACKGROUND: The major problem facing health and social care systems globally
      today is the growing challenge of an elderly population with complex health and
      social care needs. A longstanding challenge to the provision of high quality,
      effectively coordinated care for those with complex needs has been the historical
      separation of health and social care. Access to timely and accurate data about
      patients and their treatments has the potential to deliver better care at less
      cost. METHODS: To explore the way in which structural, professional and
      geographical boundaries have affected e-health implementation in health and
      social care, through an empirical study of the implementation of an electronic
      version of Single Shared Assessment (SSA) in Scotland, using three retrospective,
      qualitative case studies in three different health board locations. RESULTS:
      Progress in effectively sharing electronic data had been slow and uneven. One
      cause was the presence of established structural boundaries, which lead to
      competing priorities, incompatible IT systems and infrastructure, and poor
      cooperation. A second cause was the presence of established professional
      boundaries, which affect staffs' understanding and acceptance of data sharing and
      their information requirements. Geographical boundaries featured but less
      prominently and contrasting perspectives were found with regard to issues such as
      co-location of health and social care professionals. CONCLUSIONS: To provide
      holistic care to those with complex health and social care needs, it is essential
      that we develop integrated approaches to care delivery. Successful integration
      needs practices such as good project management and governance, ensuring system
      interoperability, leadership, good training and support, together with clear
      efforts to improve working relations across professional boundaries and
      communication of a clear project vision. This study shows that while
      technological developments make integration possible, long-standing boundaries
      constitute substantial risks to IT implementations across the health and social
      care interface which those initiating major changes would do well to consider
      before committing to the investment.

PMID- 22958224
TI  - Translation validation of a new back pain screening questionnaire (the STarT Back
      Screening Tool) in French.
AB  - BACKGROUND: Low back pain (LBP) is a major public health problem and the
      identification of individuals at risk of persistent LBP poses substantial
      challenges to clinical management. The STarT Back questionnaire is a validated
      nine-item patient self-report questionnaire that classifies patients with LBP at
      low, medium or high-risk of poor prognosis for persistent non-specific LBP. The
      objective of this study was to translate and cross-culturally adapt the English
      version of the STarT Back questionnaire into French. METHODS: The translation was
      performed using best practice translation guidelines. The following phases were
      performed: contact with the STarT Back questionnaire developers, initial
      translations (English into French), synthesis, back translations, expert
      committee review, test of the pre-final version on 44 individuals with LBP, final
      version. RESULTS: The linguistic translation required minor semantic alterations.
      The participants interviewed indicated that all items of the questionnaire were
      globally clear and comprehensible. However, 6 subjects (14%) wondered if two
      questions were related to back pain or general health. After discussion within
      the expert committee and with the developer of the STarT Back tool, it was
      decided to modify the questionnaire and to add a reference to back pain in these
      two questions. CONCLUSIONS: The French version of the STarT Back questionnaire
      has been shown to be comprehensible and adapted to the French speaking general
      population. Investigations are now required to test the psychometric properties
      (reliability, internal and external validity, responsiveness) of this translated
      version of the questionnaire.

PMID- 22958225
TI  - Open by default: a proposed copyright license and waiver agreement for open
      access research and data in peer-reviewed journals.
AB  - Copyright and licensing of scientific data, internationally, are complex and
      present legal barriers to data sharing, integration and reuse, and therefore
      restrict the most efficient transfer and discovery of scientific knowledge. Much
      data are included within scientific journal articles, their published tables,
      additional files (supplementary material) and reference lists. However, these
      data are usually published under licenses which are not appropriate for data.
      Creative Commons CC0 is an appropriate and increasingly accepted method for
      dedicating data to the public domain, to enable data reuse with the minimum of
      restrictions. BioMed Central is committed to working towards implementation of
      open data-compliant licensing in its publications. Here we detail a protocol for
      implementing a combined Creative Commons Attribution license (for copyrightable
      material) and Creative Commons CC0 waiver (for data) agreement for content
      published in peer-reviewed open access journals. We explain the differences
      between legal requirements for attribution in copyright, and cultural
      requirements in scholarship for giving individuals credit for their work through
      citation. We argue that publishing data in scientific journals under CC0 will
      have numerous benefits for individuals and society, and yet will have minimal
      implications for authors and minimal impact on current publishing and research
      workflows. We provide practical examples and definitions of data types, such as
      XML and tabular data, and specific secondary use cases for published data,
      including text mining, reproducible research, and open bibliography. We believe
      this proposed change to the current copyright and licensing structure in science
      publishing will help clarify what users - people and machines - of the published
      literature can do, legally, with journal articles and make research using the
      published literature more efficient. We further believe this model could be
      adopted across multiple publishers, and invite comment on this article from all
      stakeholders in scientific research.

PMID- 22958226
TI  - Decreased axonal transport rates in the Tg2576 APP transgenic mouse: improvement
      with the gamma-secretase inhibitor MRK-560 as detected by manganese-enhanced MRI.
AB  - Neuropil deposition of beta-amyloid (Abeta) peptides is believed to be a key
      event in the neurodegenerative process of Alzheimer's disease (AD). An early and
      consistent clinical finding in AD is olfactory dysfunction with associated
      pathology. Interestingly, transgenic amyloid precursor protein (Tg2576) mice also
      show early amyloid pathology in olfactory regions. Moreover, a recent study
      indicates that axonal transport is compromised in the olfactory system of Tg2576
      mice, as measured by manganese-enhanced magnetic resonance imaging (MEMRI). Here
      we tested whether the putative axonal transport deficit in the Tg2576 mouse model
      improves in response to a selective gamma-secretase inhibitor, N-[cis-4-[(4
      chlorophenyl)-sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1
      trifluoromethanesulfonamide (MRK-560). Tg2576 mice or wild-type (WT) littermates
      were treated daily with MRK-560 (30 MUmol/kg) or vehicle for 4 (acute) or 29 days
      (chronic). The subsequent MEMRI analysis revealed a distinct axonal transport
      dysfunction in the Tg2576 mice compared with its littermate controls.
      Interestingly, the impairment of axonal transport could be fully reversed by
      chronic administration of MRK-560, in line with the significantly lowered levels
      of both soluble and insoluble forms of Abeta found in the brain and olfactory
      bulbs (OBs) following treatment. However, no improvement of axonal transport was
      observed after acute treatment with MRK-560, where soluble but not insoluble
      forms of Abeta were reduced in the brain and OBs. The present results show that
      axonal transport is impaired in Tg2576 mice compared with WT controls, as
      measured by MEMRI. Chronic treatment in vivo with a gamma-secretase inhibitor,
      MRK-560, significantly reduces soluble and insoluble forms of Abeta, and fully
      reverses the axonal transport dysfunction.

PMID- 22958227
TI  - Incorporation of sentinel lymph node mapping in dogs with mast cell tumours: 20
      consecutive procedures.
AB  - The study hypothesis is that incorporation of sentinel lymph node (SLN) mapping
      in dogs presenting for mast cell tumour (MCT) removal would impact the
      recommended adjuvant therapy offered. Nineteen dogs were enrolled having either
      spontaneously occurring or incompletely excised MCTs. Staging included regional
      lymph node aspiration. SLN mapping was done with regional lymphoscintigraphy
      combined with intra-operative lymphoscintigraphy and blue dye. Twenty MCTs in 19
      dogs were excised with SLN mapping. Eight dogs had SLNs different from the
      closest node. Twelve dogs had metastasis in extirpated SLNs, seven occurred in
      MCTs with a MI <= 5. No correlation was noted between patient stage and the c-KIT
      proto-oncogene. Because of SLN staging, 8 of 19 dogs were offered additional
      therapy that would have otherwise been excluded. Anatomic sampling of lymph nodes
      in dogs with MCTs does not accurately reflect which lymph nodes are most likely
      to be receiving the draining tumour lymph. 

PMID- 22958228
TI  - Effects of ethanol and long-chain ethyl ester concentrations on volatile
      partitioning in a whisky model system.
AB  - Ethanolic atmospheric pressure chemical ionization mass spectrometry (APCI-MS)
      was used to analyze the headspace concentrations of a test set of 14 whisky
      volatile compounds above a series of aqueous ethanolic solutions differing in
      alcohol content (5-40% ABV) and with regard to concentration of ethyl
      hexadecanoate (0-500 mg/L). The latter was selected to represent the long-chain
      ethyl esters found at various concentrations in new-make spirit. Headspace ion
      intensities were modeled against ethanol and ethyl hexadecanoate concentrations
      as factors. A separate model was prepared for each compound. Not surprisingly,
      ethanol content in the range of 5-40% ABV had a significant effect (P < 0.0001)
      on headspace volatile concentrations of all volatile compounds, whereas the ethyl
      hexadecanoate concentration had a selective effect of reducing headspace
      concentrations of the more hydrophobic compounds (log P > 2.5). This finding is
      discussed in terms of the "structuring" effects of ethyl hexadecanoate when
      present above critical micelle concentration, leading to the selective
      incorporation of hydrophobic volatile compounds into the interior of micelle-like
      structures. Data presented illustrate that dilution of whiskies to 23% ABV for
      "nosing" in the presence of long-chain ethyl esters is likely to change the
      balance of volatile compounds in the headspace and thus the perceived aroma
      character. 

PMID- 22958229
TI  - NG6: Integrated next generation sequencing storage and processing environment.
AB  - BACKGROUND: Next generation sequencing platforms are now well implanted in
      sequencing centres and some laboratories. Upcoming smaller scale machines such as
      the 454 junior from Roche or the MiSeq from Illumina will increase the number of
      laboratories hosting a sequencer. In such a context, it is important to provide
      these teams with an easily manageable environment to store and process the
      produced reads. RESULTS: We describe a user-friendly information system able to
      manage large sets of sequencing data. It includes, on one hand, a workflow
      environment already containing pipelines adapted to different input formats (sff,
      fasta, fastq and qseq), different sequencers (Roche 454, Illumina HiSeq) and
      various analyses (quality control, assembly, alignment, diversity studies,...)
      and, on the other hand, a secured web site giving access to the results. The
      connected user will be able to download raw and processed data and browse through
      the analysis result statistics. The provided workflows can easily be modified or
      extended and new ones can be added. Ergatis is used as a workflow building,
      running and monitoring system. The analyses can be run locally or in a cluster
      environment using Sun Grid Engine. CONCLUSIONS: NG6 is a complete information
      system designed to answer the needs of a sequencing platform. It provides a user
      friendly interface to process, store and download high-throughput sequencing
      data.

PMID- 22958230
TI  - Novel cerebrospinal fluid and serum autoantibody targets for clinically isolated
      syndrome.
AB  - Limited information is available on the identity of antigens targeted by
      antibodies present in cerebrospinal fluid (CSF) of patients with clinically
      isolated syndrome (CIS). The aim of this study was to identify novel antigens for
      CIS and investigate their prognostic potential to predict conversion to multiple
      sclerosis (MS). We applied serological antigen selection (SAS) to identify
      antigens interacting with antibodies present in the pooled CSF from four CIS
      patients, who developed MS. Antibody reactivity towards CIS antigens identified
      by SAS was tested in CSF and serum from patients with CIS (n = 123/n = 108), MS
      (n = 65/n = 44), and other (inflammatory) neurological diseases (n = 75/n = 38)
      as well as in healthy control sera (n = 44). Using SAS, a panel of six novel CIS
      candidate antigens was identified. CSF antibody reactivity was detected in both
      CIS and relapsing-remitting (RR) MS. Serum reactivity was significantly increased
      in CIS and RR-MS as compared with controls (p = 0.03). For two antigens, the
      frequency of antibody-positive patients was higher in CIS patients who converted
      to MS as compared with CIS patients without conversion. We identified novel CIS
      antigens to which antibody reactivity was primarily detected in CIS and RR-MS as
      compared to controls. Possible prognostic potential could be demonstrated for two
      antigens.

PMID- 22958231
TI  - Inherent possibility of refraction error for phacovitrectomy.

PMID- 22958232
TI  - Use and performance of premounted stents compared to nonpremounted stents in
      pediatric and adult congenital cardiac catheterization.
AB  - OBJECTIVES: We sought to characterize the use, efficacy, and performance
      characteristics of premounted stents relative to nonpremounted stents when used
      during congenital cardiac catheterization. BACKGROUND: Endovascular stent
      implantation is an effective means of relieving vascular obstruction in patients
      with congenital heart disease. However, stent implantation is technically
      challenging and important complications occur. Premounted stents appear to offer
      many advantages relative to their nonpremounted counterparts, and it has been
      suggested that the use of premounted stents is associated with fewer
      complications. However, translation of these potential benefits into procedural
      or clinical success has been poorly examined and the data are conflicting.
      METHODS: All stent placements performed between January 1, 1999 and December 31,
      2009 were reviewed. Analysis of technical success, hemodynamic success and
      complications was performed. RESULTS: 416 stents were placed over the 10 year
      period. 158 (38%) were premounted. There was no apparent trend in the frequency
      of use of premounted stents over the study period. Implanted premounted stents
      were smaller in diameter than nonpremounted stents 4.9 mm +/- 1.8 versus 13.9 mm
      +/- 3.7, and the site of stent placement differed significantly. Unadjusted and
      adjusted analysis of technical success with respect to the precision of stent
      placement, hemodynamic success, and complications showed no difference between
      premounted and non-premounted stents. CONCLUSIONS: We found no difference between
      premounted and nonpremounted stents with respect to procedural and hemodynamic
      success or complications. Nevertheless, there remain practical advantages to the
      use of premounted stents that may justify their expanding role in congenital
      cardiac catheterization.

PMID- 22958233
TI  - Patient-reported outcome in colorectal health and disease.

PMID- 22958234
TI  - Midterm results after arterial switch operation for transposition of the great
      arteries: a single centre experience.
AB  - BACKGROUND: The arterial switch operation (ASO) has become the surgical approach
      of choice for d-transposition of the great arteries (d-TGA). There is, however an
      increased incidence of midterm and longterm adverse sequelae in some survivors.
      In order to evaluate operative risk and midterm outcome in this population, we
      reviewed patients who underwent ASO for TGA at our centre. METHODS: In this
      retrospective study 52 consecutive patients with TGA who underwent ASO between
      04/1991 and 12/1999 were included. To analyze the predictors for mortality and
      adverse events (coronary stenoses, distortion of the pulmonary arteries,
      dilatation of the neoaortic root, and aortic regurgitation), a multivariate
      analysis was performed. The follow-up time was ranged from 1-10 years (mean 5
      years, cumulative 260 patient-years). RESULTS: All over mortality rate was 15.4%
      and was only observed in the early postoperative period till 1994. The predictors
      for poor operative survival were low APGAR-score, older age at surgery, and
      necessity of associated surgical procedures. Late re-operations were necessary in
      6 patients (13.6%) and included a pulmonary artery patch enlargement due to
      supravalvular stenosis (n = 3), coronary revascularisation due to coronary
      stenosis in a coronary anatomy type E, aortic valve replacement due to neoaortic
      valve regurgitation (n = 2), and patch-plasty of a pulmonary vein due to
      obstruction (n = 1). The dilatation of neoaortic root was not observed in the
      follow up. CONCLUSIONS: ASO remains the procedure of choice for TGA with
      acceptable early and late outcome in terms of overall survival and freedom of
      reoperation. Although ASO is often complex and may be associated with morbidity,
      most patients survived without major complications even in a small centre.

PMID- 22958235
TI  - Increased blood pressure reactions to acute mental stress are associated with 16
      year cardiovascular disease mortality.
AB  - Exaggerated cardiovascular reactions to acute psychological stress may be
      involved in the etiology of cardiovascular pathology. The present analysis
      examined the association between the magnitude of systolic and diastolic blood
      pressure reactions to stress and cardiovascular disease mortality. Participants
      were 431 (229 women) from the West of Scotland Twenty-07 Study, aged 63 years at
      the time of stress testing, where blood pressure was measured during resting
      baseline and mental arithmetic stress. Participants' vital status was tracked for
      the next 16 years, during which time 38 had died of cardiovascular disease. Both
      systolic and diastolic blood pressure reactions were positively associated with
      cardiovascular disease mortality. This association could reflect the long-term
      erosive effects of exaggerated reactivity on the vasculature as well as its short
      term capacity to trigger acute cardiovascular events.

PMID- 22958236
TI  - Suture boots: an aid for the injection of onabotulinum toxin a for primary focal
      hyperhidrosis.
AB  - Primary focal hyperhidrosis is a difficult problem for adults, children, and
      adolescents, causing significant impairment in quality of life. Onabotulinum
      toxin A injection is an effective third-line treatment for primary focal
      hyperhidrosis. Here we describe a technique to ensure adequate depth of botulinum
      toxin placement in the dermis using suture boots as an aid for injection.

PMID- 22958237
TI  - VA LOVIT II: a protocol to compare low vision rehabilitation and basic low
      vision.
AB  - PURPOSE: To compare the effectiveness of low vision rehabilitation (LVR) and
      basic low vision (LV) in a single masked multicentre randomised controlled trial
      (RCT). METHODS: Three hundred and thirty patients eligible for US. Veterans
      Affairs (VA) healthcare services with primary eye diagnosis (better-seeing eye)
      of macular disease and best-corrected distance visual acuity of 0.40-1.00 logMAR
      (6/15 to 6/60 or 20/50 to 20/200 Snellen) are being enrolled at seven VA
      facilities. All participants receive an optometric LV examination; and they are
      eligible to receive the same LV devices that are provided without charge. In LVR,
      a LV therapist dispenses devices and provides 2 or 3 (11/2 to 21/2 h) therapy
      sessions with assigned homework to teach effective use of remaining vision and LV
      devices. Contact time with the therapist depends upon the devices prescribed and
      the patient's progress in learning the skills that are taught. In basic LV,
      devices are dispensed by the optometrist without LV therapy. Contact time for
      dispensing is one hour or less depending on LV devices prescribed. The primary
      outcome measure is a comparison of the changes in visual reading ability
      (estimated from patients' difficulty ratings of reading items on the VA LV VFQ-48
      questionnaire) between the treatment and control arms from pre-intervention
      baseline to 4 months (2 months after completion of treatment). Secondary outcome
      measures are changes in overall visual ability, visual ability domain scores
      calculated from subsets of items (mobility, visual information processing and
      visual motor skills), Short Form-36, and Minnesota Low Vision Reading Test
      scores. Cost-effectiveness analysis will be conducted using VA LV VFQ-48 scores
      and QALYS computed from EuroQol scores. RESULTS: A total of 137 patients
      representing 41.5% of the study target of 330 patients were randomised from
      October 2010 to March 2012. Among those 137 patients, mean age was 80.2 (S.D. +/-
      9.9) years at enrollment; 97.1% of the patients were males; 94.2% were white.
      Mean best corrected VA was 0.65 (S.D. +/- 0.3) logMAR (approximately Snellen 6/27
      or 20/90) at baseline. CONCLUSIONS: LOVIT II is the first multicentre RCT
      comparing the effectiveness and cost-effectiveness of LVR and basic LV for
      patients with macular diseases and near normal or moderate levels of visual
      impairment.

PMID- 22958238
TI  - Prolongation of length of stay and Clostridium difficile infection: a review of
      the methods used to examine length of stay due to healthcare associated
      infections.
AB  - BACKGROUND: It is believed that Clostridium difficile infection (CDI)
      contributes to a prolongation of length of stay (LOS). Recent literature suggests
      that models previously used to determine LOS due to infection have overestimated
      LOS, compared to newer statistical models. The purpose of this review is to
      understand the impact that CDI has on LOS and in doing so, describe the
      methodological approaches used. AIM: First, to investigate and describe the
      reported prolongation of LOS in hospitalised patients with CDI. Second, to
      describe the methodologies used for determining excess LOS. METHODS: An
      integrative review method was used. Papers were reviewed and analysed
      individually and themes were combined using integrative methods. RESULTS:
      Findings from all studies suggested that CDI contributes to a longer LOS in
      hospital. In studies that compared persons with and without CDI, the difference
      in the LOS between the two groups ranged from 2.8days to 16.1days. Potential
      limitations with data analysis were identified, given that no study fully
      addressed the issue of a time-dependent bias when examining the LOS. Recent
      literature suggests that a multi-state model should be used to manage the issue
      of time-dependent bias. CONCLUSION: Studies examining LOS attributed to CDI
      varied considerably in design and data collected. Future studies examining LOS
      related to CDI and other healthcare associated infections should consider
      capturing the timing of infection in order to be able to employ a multi-state
      model for data analysis.

PMID- 22958239
TI  - Reward processing in autism: a thematic series.
AB  - This thematic series presents theoretical and empirical papers focused on
      understanding autism from the perspective of reward processing deficits. Although
      the core symptoms of autism have not traditionally been conceptualized with
      respect to altered reward-based processes, it is clear that brain reward
      circuitry plays a critical role in guiding social and nonsocial learning and
      behavior throughout development. Additionally, brain reward circuitry may respond
      to social sources of information in ways that are similar to responses to primary
      rewards, and recent clinical data consistently suggest abnormal behavioral and
      neurobiologic responses to rewards in autism. This thematic series presents
      empirical data and review papers that highlight the utility of considering autism
      from the perspective of reward processing deficits. Our hope is that this novel
      framework may further elucidate autism pathophysiology, with the ultimate goal of
      yielding novel insights with potential therapeutic implications.

PMID- 22958240
TI  - Low molecular weight heparin decreases the permeability of glomerular endothelial
      cells when exposed to pre-eclampsia serum in vitro.
AB  - AIM: Low molecular weight heparin (LMWH) has been used to treat certain kidney
      diseases such as pre-eclampsia, in which extensive levels of proteinuria are
      associated with dysfunction of glomerular endothelium. In our study, we
      investigated whether LMWH could affect the permeability of and ET-1 expression in
      human glomerular endothelial cells (GEnC) incubated with pre-eclampsia serum.
      METHODS: Serum from pre-eclampsia patients was collected and incubated with GEnC
      in the absence or presence of LMWH. We assessed the permeability of glomerular
      endothelial monolayer by measuring the amount of bovine serum albumin (BSA) that
      crosses into the lower chamber of a trans-well device. In addition, we measured
      ET-1 mRNA expression levels in and proliferation and apoptotic rates of GEnC
      exposed to pre-eclampsia serum with or without LMWH. RESULTS: The permeability of
      ET-1 mRNA expression in GEnC increased upon incubation with pre-eclampsia serum,
      but decreased significantly when LMWH was added. The presence of LMWH did not
      alter the proliferation and apoptosis of GEnC incubated with pre-eclampsia serum.
      CONCLUSION: Low molecular weight heparin maintains the integrity of the kidney
      probably by strengthening the defence of glomerular endothelium.

PMID- 22958241
TI  - Control of antimicrobial resistance in Canada: any lessons to learn?
AB  - BACKGROUND: Over the past 15 years, repeated national meetings have developed
      recommendations for a Canadian antimicrobial resistance strategy. Despite this,
      in 2011 there is no comprehensive, integrated national program with appropriate
      governance and funding to address antimicrobial resistance. FINDINGS: The Public
      Health Agency of Canada supports a reference laboratory for diagnosis and
      characterization of selected resistant strains, targeted surveillance programs
      which monitor resistance trends for selected animal and human organisms,
      development of national infection control guidelines including for antimicrobial
      resistant organisms, and a few local pilot projects to address community acquired
      MRSA. Sporadic programs of variable intensity and quality are supported by some
      provinces, health regions and individual facilities but these are not
      comprehensive, standardized or integrated. Individual researchers and research
      groups, however, have published substantial information describing the prevalence
      and impact of resistance in Canada. CONCLUSIONS: Current review of activities by
      the Public Health Agency of Canada and initiatives by the National Coordinating
      Centre for Infectious Diseases may move the country forward in developing an
      effective national approach to address antimicrobial resistance.

PMID- 22958242
TI  - Effects of musical training on the early auditory cortical representation of
      pitch transitions as indexed by change-N1.
AB  - The effects of musical training on the early auditory cortical response to pitch
      transitions in music were investigated by use of the change-N1 component of
      auditory event-related potentials. Musicians and non-musicians were presented
      with music stimuli comprising a melody and a harmony under various listening
      conditions. First, when the subjects played a video game and were instructed to
      ignore the auditory stimuli, the onset of stimuli elicited a typical, fronto
      central onset-N1, whereas melodic and harmonic pitch transitions within the
      stimuli elicited so-called change-N1s that were more posterior in scalp
      distribution. The pitch transition change-N1s, but not onset-N1, were enhanced in
      musicians. Second, when the listeners attended to the same stimuli as above to
      detect infrequently occurring target stimuli, the change-N1 elicited by pitch
      changes (in non-target stimuli) was augmented, in non-musicians only when the
      target was easily detectable, and in both musicians and non-musicians when it was
      difficult to detect. Thus, the early, obligatory cortical response to pitch
      transitions during passive listening was chronically enhanced by training in
      musicians, and, reflecting this training-induced enhancement, the task-related
      modulation of this response was also different between musicians and non
      musicians. These results are the first to demonstrate the long-term effects of
      training, short-term effects of task and the effects of their interaction on the
      early (~100-ms) cortical processing of pitch transitions in music. The scalp
      distributions of these enhancement effects were generally right dominant at
      temporal electrode sites, suggesting contributions from the radially oriented
      subcomponent of change-N1, namely, the Tb (N1c) wave of the T-complex.

PMID- 22958243
TI  - A novel method for rapid and reliable detection of complex vertebral malformation
      and bovine leukocyte adhesion deficiency in Holstein cattle.
AB  - BACKGROUND: Complex vertebral malformation (CVM) and bovine leukocyte adhesion
      deficiency (BLAD) are two autosomal recessive lethal genetic defects frequently
      occurring in Holstein cattle, identifiable by single nucleotide polymorphisms.
      The objective of this study is to develop a rapid and reliable genotyping assay
      to screen the active Holstein sires and determine the carrier frequency of CVM
      and BLAD in Chinese dairy cattle population. RESULTS: We developed real-time PCR
      based assays for discrimination of wild-type and defective alleles, so that
      carriers can be detected. Only one step was required after the DNA extraction
      from the sample and time consumption was about 2 hours. A total of 587 Chinese
      Holstein bulls were assayed, and fifty-six CVM-carriers and eight BLAD-carriers
      were identified, corresponding to heterozygote carrier frequencies of 9.54% and
      1.36%, respectively. The pedigree analysis showed that most of the carriers could
      be traced back to the common ancestry, Osborndale Ivanhoe for BLAD and Pennstate
      Ivanhoe Star for CVM. CONCLUSIONS: These results demonstrate that real-time PCR
      is a simple, rapid and reliable assay for BLAD and CVM defective allele
      detection. The high frequency of the CVM allele suggests that implementing a
      routine testing system is necessary to gradually eradicate the deleterious gene
      from the Chinese Holstein population.

PMID- 22958245
TI  - Indices and COPD.

PMID- 22958246
TI  - Changing realities in emerging zoonoses.

PMID- 22958247
TI  - 6th International Conference on Emerging Zoonoses.
AB  - The 6th International Conference on Emerging Zoonoses, held at Cancun, Mexico, 24
      27 February 2011, offered 84 participants from 18 countries, a snapshot of
      current research in numerous zoonoses caused by viruses, bacteria or prions. Co
      chaired by Professors Heinz Feldmann and Jurgen Richt, the conference explored 10
      topics: (i) The ecology of emerging zoonotic diseases; (ii) The role of wildlife
      in emerging zoonoses; (iii) Cross-species transmission of zoonotic pathogens;
      (iv) Emerging and neglected influenza viruses; (v) Haemorrhagic fever viruses;
      (vi) Emerging bacterial diseases; (vii) Outbreak responses to zoonotic diseases;
      (viii) Food-borne zoonotic diseases; (ix) Prion diseases; and (x) Modelling and
      prediction of emergence of zoonoses. Human medicine, veterinary medicine and
      environmental challenges are viewed as a unity, which must be considered under
      the umbrella of 'One Health'. Several presentations attempted to integrate the
      insights gained from field data with mathematical models in the search for
      effective control measures of specific zoonoses. The overriding objective of the
      research presentations was to create, improve and use the tools essential to
      address the risk of contagions in a globalized society. In seeking to fulfil this
      objective, a three-step approach has often been applied: (i) use cultured cells,
      model and natural animal hosts and human clinical models to study infection; (ii)
      combine traditional histopathological and biochemical approaches with functional
      genomics, proteomics and computational biology; and (iii) obtain signatures of
      virulence and insights into mechanisms of host defense response, immune evasion
      and pathogenesis. This meeting review summarizes 39 of the conference
      presentations and mentions briefly the 16 articles in this Special Supplement,
      most of which were presented at the conference in earlier versions. The full
      affiliations of all presenters and many colleagues have been included to
      facilitate further inquiries from readers.

PMID- 22958249
TI  - Lassa fever in West Africa: evidence for an expanded region of endemicity.
AB  - Lassa virus (LASV) is endemic in Sierra Leone, Guinea and Liberia (known as the
      Mano River region) and Nigeria and Lassa fever cases from these countries are
      being reported annually. Recent investigations have found evidence for an
      expanded endemicity zone between the two known Lassa endemic regions indicating
      that LASV is more widely distributed throughout the Tropical Wooded Savanna
      ecozone in West Africa.

PMID- 22958248
TI  - Lessons from emergence of A/goose/Guangdong/1996-like H5N1 highly pathogenic
      avian influenza viruses and recent influenza surveillance efforts in southern
      China.
AB  - Southern China is proposed as an influenza epicentre. At least two of the three
      pandemics in the last century, including 1957 and 1968 influenza pandemics,
      originated from this area. In 1996, A/goose/Guangdong/1/1996 (H5N1), the
      precursor of currently circulating highly pathogenic H5N1 avian influenza viruses
      (HPAIVs) was identified in farmed geese in southern China. These H5N1 HPAIVs have
      been spread across Asia, Europe and Africa and poses a continuous threat to both
      animal and human health. However, how and where this H5N1 HPAIV emerged are not
      fully understood. In the past decade, many influenza surveillance efforts have
      been carried out in southern China, and our understanding of the genetic
      diversity of non-human influenza A viruses in this area has been much better than
      ever. Here, the historical and first-hand experimental data on
      A/goose/Guangdong/1/1996(H5N1)-like HPAIVs are reviewed within the context of the
      findings from recent surveillance efforts on H5N1 HPAIVs and other non-human
      influenza A viruses. Such a retrospective recapitulation suggests that long-term
      and systematic surveillance programmes should continue to be implemented in
      southern China that the wet markets on the animal-human interface shall be the
      priority area and that the surveillance on the animal species bridging the
      interface between wildlife and domestic animal populations and the interface
      between the aquatics and territories shall be the strengthened.

PMID- 22958250
TI  - Beyond Lyme: aetiology of tick-borne human diseases with emphasis on the south
      eastern United States.
AB  - Since its emergence in the north-eastern and upper mid-western United States in
      the 1970s, Lyme disease, caused by Borrelia burgdorferi, has captured the
      public's attention as the nation's most prevalent vector-borne zoonotic disease.
      In contrast, recent publications on tick-pathogen systems in the eastern United
      States, and findings from Department of Defense investigations of ticks found
      biting military personnel, indicate that residents of the south-eastern United
      States are primarily at risk from emerging diseases caused by tick-borne
      pathogens other than B. burgdorferi. The risk of contracting these diseases
      varies greatly among states as a consequence of regional variation in the
      abundance of the key vector tick species. Moreover, this risk is changing,
      because tick distributions are in flux. To improve health outcomes, health
      providers need better information and awareness regarding which tick species bite
      humans in each state and which zoonotic pathogens are prevalent in these ticks.
      Effective diagnosis, treatment, control and reporting of tick-borne disease in
      the south-eastern United States require that health providers think 'beyond Lyme'
      and consider the marked regional differences in the tick species that bite humans
      and in the pathogens that these ticks carry.

PMID- 22958251
TI  - Spotted fever group rickettsiae: a brief review and a Canadian perspective.
AB  - Spotted fever group rickettsioses (SFGR) are infections caused by established and
      emerging human pathogens worldwide. These rickettsial agents are transmitted to
      humans via arthropods and may result in mild to severe and potentially fatal
      diseases. Spotted fever group rickettsioses are characterized by similar clinical
      features, including fever, rash, headache and myalgias, with the development of
      an inoculation eschar in many, but not all cases. Endemic rickettsial infections
      do occur but are infrequent in Canada, in contrast to the United States, where
      these infections are far more prevalent. Travel-associated rickettsioses,
      however, are being diagnosed with increasing frequency in Canadian travellers
      returning from international trips abroad, in particular in travellers returning
      from Africa. The diagnosis of rickettsial infections can be challenging owing to
      the non-specific nature of the clinical symptoms and the requirement for
      specialized testing. Serology cannot distinguish between the approximately 20
      spotted fever group rickettsial species currently known or suspected to be
      capable of causing human infection. Molecular testing is required to determine
      the rickettsial species responsible for infection, but requires greater effort on
      the part of the clinician to collect appropriate samples, including cutaneous
      skin swabs from under the eschar or skin punch biopsies of the eschar or rash.
      Infections with spotted fever group rickettsiae likely occur more commonly than
      currently recognized and should be considered in patients with appropriate
      symptoms and exposure histories.

PMID- 22958252
TI  - Emerging and exotic zoonotic disease preparedness and response in the United
      States - coordination of the animal health component.
AB  - For the response to a zoonotic disease outbreak to be effective, animal health
      authorities and disease specialists must be involved. Animal health measures are
      commonly directed at known diseases that threaten the health of animals and
      impact owners. The measures have long been applied to zoonotic diseases,
      including tuberculosis and brucellosis, and can be applied to emerging diseases.
      One Health (veterinary, public, wildlife and environmental health) and all
      hazards preparedness work have done much to aid interdisciplinary understanding
      and planning for zoonotic diseases, although further improvements are needed.
      Actions along the prevention, preparedness, response and recovery continuum
      should be considered. Prevention of outbreaks consists largely of import controls
      on animals and animal products and biosecurity. Preparedness includes situational
      awareness, research, tool acquisition, modelling, training and exercises, animal
      movement traceability and policy development. Response would include detection
      systems and specialized personnel, institutions, authorities, strategies, methods
      and tools, including movement control, depopulation and vaccination if available
      and appropriate. The specialized elements would be applied within a general
      (nationally standardized) system of response. Recovery steps begin with
      continuity of business measures during the response and are intended to restore
      pre-event conditions. The surveillance for novel influenza A viruses in swine and
      humans and the preparedness for and response to the recent influenza pandemic
      illustrate the cooperation possible between the animal and public health
      communities.

PMID- 22958253
TI  - Monitoring of West Nile virus infections in Germany.
AB  - West Nile virus (WNV) is a flavivirus that is maintained in an enzootic cycle
      between ornithophilic mosquitoes, mainly of the Culex genus, and certain wild
      bird species. Other bird species like ravens, jays and raptors are highly
      susceptible to the infection and may develop deadly encephalitis, while further
      species of birds are only going through subclinical infection. The objective of
      this study was to continue in years 2009-2011 the serological and molecular
      surveillance in wild birds in Germany (see Vector Borne Zoonotic Dis. 10, 639)
      and to expand these investigations for the first time also to sera from domestic
      poultry and horses collected between 2005 and 2009. All three cohorts function as
      indicators for the endemic circulation of WNV. The presence of WNV-specific
      antibodies was detected in all samples by virus neutralization test (VNT),
      indirect immunofluorescence test (IFT) and/or enzyme-linked immunosorbent assay
      (ELISA). The presence of WNV genomes was monitored in relevant sera using two qRT
      PCRs that amplify lineage 1 and 2 strains. A total of 364 migratory and resident
      wild bird serum samples (with emphasis on Passeriformes and Falconiformes) as
      well as 1119 serum samples from domestic poultry and 1282 sera from horses were
      analysed. With the exception of one hooded crow, antibody carriers were
      exclusively found in migratory birds, but not in resident birds/domestic poultry
      or in local horses. Crows are facultative, short-distance winter migrants in
      Germany. WNV-specific nucleic acids could not be demonstrated in any of the
      samples. According to these data, there is no convincing evidence for indigenous
      WNV infections in equines and in wild/domestic birds in Germany. However, since a
      few years, WNV infections are endemic in other European countries such as
      Austria, Hungary, Greece and Italy, a state-of-the-art surveillance system for
      the detection of incursions of WNV into Germany deems mandatory.

PMID- 22958254
TI  - Epidemiological survey of Trypanosoma cruzi infection in domestic owned cats from
      the tropical southeast of Mexico.
AB  - American trypanosomiasis is an infectious disease of importance for public health
      and caused by the protozoa Trypanosoma cruzi mainly transmitted by triatomine
      bugs. The precise role of cats in the peridomestic transmission of T. cruzi and
      the mechanism by which cats become infected remain uncertain. The objective of
      this work was to determine the prevalence of T. cruzi infection in domestic cats
      from an urban area of tropical Mexico by serological and molecular methods and
      evaluate associated risk factors. A total of 220 domestic cats from Merida
      Yucatan, Mexico, were studied. Animals older than 3 months were blood sampled.
      Serum and DNA were obtained. Specific T. cruzi IgG antibodies were detected using
      a commercial indirect ELISA with an anti-cat antibody HRP labelled. Positive
      cases were confirmed by Western blot (WB). Polymerase chain reaction (PCR) was
      also performed using the primers TC1 and TC2. From the 220 cats, 8.6% had
      antibodies against T. cruzi using ELISA test and later confirmed by WB. In 75
      cats (34%), the sequence of ADNk of T. cruzi was amplified. The bad-regular body
      condition was the only risk factor associated with PCR positive to T.cruzi (P <
      0.001). In Mexico, there are no previous epidemiological reports that demonstrate
      the importance of the cat as a reservoir of T. cruzi. Few individuals were
      identified with a serological response because they were probably at an early
      stage of infection or antibodies were not detected because they could be
      immunocompromised (FIV, FeLV or others). It is necessary to monitor PCR-positive
      patients and conduct further studies for better understanding of the epidemiology
      and pathogenesis of Chagas disease in domestic cats.

PMID- 22958255
TI  - Atypical severe Puumala hantavirus infection and virus sequence analysis of the
      patient and regional reservoir host.
AB  - Nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) is a mild variant
      of haemorrhagic fever with renal syndrome, which is endemic in Germany. We
      describe the case of a 67-year-old man initially presenting with acute bilateral
      angle-closure glaucoma, an atypical clinical presentation of PUUV infection.
      Subsequently, the patient developed a severe course of disease additionally
      complicated by profound hepatitis and interstitial nephritis, both phenomena
      which are rarely described in association with hantavirus infection. Serologic
      diagnosis was complicated by delayed antibody production until the 10th day of
      illness; however, PUUV RNA was detectable early in disease. To further analyse
      this unusual case, sequencing of the PUUV S segment was performed from the
      patient and regional reservoir host which showed a close relation.

PMID- 22958256
TI  - How Ebola virus counters the interferon system.
AB  - Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe
      haemorrhagic fever in afflicted individuals with high case-fatality rates.
      Neither vaccines nor therapeutics are at present available to combat EBOV
      infection, making the virus a potential threat to public health. To devise
      antiviral strategies, it is important to understand which components of the
      immune system could be effective against EBOV infection. The interferon (IFN)
      system constitutes a key innate defence against viral infections and prevents
      development of lethal disease in mice infected with EBOV strains not adapted to
      this host. Recent research revealed that expression of the host cell IFN
      inducible transmembrane proteins 1-3 (IFITM1-3) and tetherin is induced by IFN
      and restricts EBOV infection, at least in cell culture model systems. IFITMs,
      tetherin and other effector molecules of the IFN system could thus pose a potent
      barrier against EBOV spread in humans. However, EBOV interferes with signalling
      events required for human cells to express these proteins. Here, we will review
      the strategies employed by EBOV to fight the IFN system, and we will discuss how
      IFITM proteins and tetherin inhibit EBOV infection.

PMID- 22958257
TI  - Leptospiral uveitis - there is more to it than meets the eye!
AB  - Leptospirosis, caused by pathogenic species of genus Leptospira, is a highly
      prevalent zoonotic disease throughout many parts of the world, and an important
      emerging disease within the United States. Uveitis is a common complication of
      systemic infection in humans. A similar condition in horses is characterized by
      recurrent bouts of inflammation. In this article, we review advances in our
      understanding of leptospiral uveitis and its pathogenic mechanisms.

PMID- 22958258
TI  - Virus-like particle-based countermeasures against Rift Valley fever virus.
AB  - Rift Valley fever virus (RVFV) is an arbovirus that causes significant morbidity
      and mortality in both humans and livestock. With increased world travel and the
      threat of bioterrorism, there is a real risk of RVFV spreading to naive
      geographical areas (Trans. R. Soc. Trop. Med. Hyg., 73, 1979, 618; MMWR Morb.
      Mortal. Wkly Rep., 49, 2000, 905). The introduction of RVFV would cause critical
      public health, agricultural and economic damage. Despite the clear need for an
      efficacious vaccine, there are no United States (US) Food and Drug Administration
      or US Department of Agriculture approved vaccines against RVFV. To address this
      need, a virus-like particle (VLP)-based vaccine candidate was developed. First, a
      non-replicating chimeric RVF VLP vaccine candidate was generated that protected
      mice and rats against a lethal RVFV challenge. This was followed by the
      development and optimization of conditions for production of RVF VLPs in insect
      and mammalian cells. Immunological studies demonstrated that VLP-based vaccine
      candidates elicit both humoral and cellular immune responses. Subsequent
      challenge studies using a lethal wild-type RVFV strain under high-containment
      conditions showed that RVF VLP vaccine candidates can completely protect mice and
      rats.

PMID- 22958259
TI  - Flexibility of mobile laboratory unit in support of patient management during the
      2007 Ebola-Zaire outbreak in the Democratic Republic of Congo.
AB  - The mobile laboratory provides a safe, rapid and flexible platform to provide
      effective diagnosis of Ebola virus as well as additional differential diagnostic
      agents in remote settings of equatorial Africa. During the 2007 Democratic
      Republic of Congo outbreak of Ebola-Zaire, the mobile laboratory was set up in
      two different locations by two separate teams within a day of equipment arriving
      in each location. The first location was in Mweka where our laboratory took over
      the diagnostic laboratory space of the local hospital, whereas the second
      location, approximately 50 km south near Kampungu at the epicentre of the
      outbreak, required local labour to fabricate a tent structure as a suitable pre
      existing structure was not available. In both settings, the laboratory was able
      to quickly set up, providing accurate and efficient molecular diagnostics (within
      3 h of receiving samples) for 67 individuals, including four cases of Ebola,
      seven cases of Shigella and 13 cases of malaria. This rapid turn-around time
      provides an important role in the support of patient management and
      epidemiological surveillance.

PMID- 22958260
TI  - Emerging antimicrobial resistance in commensal Escherichia coli with public
      health relevance.
AB  - In 2009, 1462 Escherichia coli isolates were collected in a systematic resistance
      monitoring approach from primary production, slaughterhouses and at retail and
      evaluated on the basis of epidemiological cut-off values. Besides resistance to
      antimicrobial classes that have been extensively used for a long time (e.g.
      sulphonamides and tetracyclines), resistance to (fluoro)quinolones and third
      generation cephalosporins was observed. While in the poultry production chain the
      majority (60%) of isolates from laying hens was susceptible to all antimicrobials
      tested, most isolates from broilers, chicken meat and turkey meat showed
      resistance to at least one (85-93%) but frequently even to several antimicrobial
      classes (73-84%). In the cattle and pig production chain, the share of isolates
      showing resistance to at least one antimicrobial was lowest (16%) in dairy cows,
      whereas resistance to at least one antimicrobial ranged between 43% and 73% in
      veal calves, veal and pork. Resistance rates to ciprofloxacin and nalidixic acid
      in isolates from broilers were 41.1% and 43.1%, respectively. Likewise, high
      resistance rates to (fluoro)quinolones were observed in isolates from chicken
      meat and turkey meat. In contrast, ciprofloxacin resistance was less frequent in
      E. coli isolates from the cattle and pig production chain with highest rate in
      veal calves (13.3%). Highest resistance rates to cephalosporins were observed in
      broilers and chicken meat, with 5.9% and 6.2% of the isolates showing resistance.
      In dairy cattle and veal, no isolates with cephalosporin resistance were
      detected, whereas 3.3% of the isolates from veal calves showed resistance to
      ceftazidime. Resistance to (fluoro)quinolones and cephalosporins in E. coli
      isolates is of special concern because they are critically important
      antimicrobials in human antimicrobial therapy. The emergence of this resistance
      warrants increased monitoring. Together with continuous monitoring of
      antimicrobial usage, management strategies should be regularly assessed and
      adapted.

PMID- 22958261
TI  - American trypanosomiasis infection in fattening pigs from the south-east of
      Mexico.
AB  - American Trypanosomiasis (AT) is an infectious parasitic disease produced by the
      protozoa Trypanosoma cruzi (T. cruzi). Infection is acquired by vectorial via but
      can also be transmitted congenitally, by ingestion of an infected host, by
      transfusion with contaminated blood or transplant of organs from an infected
      donor. Currently, AT is widely distributed from the South of the United States to
      South America. In Mexico, the presence of the parasite has been reported
      throughout the country where several reservoirs such as dogs, opossums, rats and
      cats have been identified. Yucatan is in the south-east of Mexico where AT is
      endemic and has been reported since 1940s. There is little information about the
      role of pigs as reservoirs of T. cruzi. The frequency of specific antibodies
      against T. cruzi was determined in fattening pigs from Yucatan, Mexico. After
      sampling in the 3 main areas of pig production in the state, IgG ELISA and
      Western blot were performed to identify seropositive cases. Association of farm
      size, farm area and production system with infected pigs was evaluated. From 273
      sampled pigs, 5.4% (n = 15) positive cases were found. No association with
      evaluated factors and infected pigs was found. Pigs are also reservoirs of T.
      cruzi in the studied area. These findings are considered important to improve
      vectorial control in the area in order to avoid the parasite infection in animal
      populations destined for human consumption and avoid further transmission to
      humans.

PMID- 22958262
TI  - Modelling transmission of bovine tuberculosis in red deer and wild boar in
      Normandy, France.
AB  - In early 2001, Mycobacterium bovis infection was confirmed in red deer (RD)
      (Cervus elaphus) shot in Normandy region, France. An epidemiological survey
      conducted during the following hunting season in two connected forests confirmed
      the occurrence of the disease in both free-ranging RD and wild boar (WB) (Sus
      scrofa). This was the first detected bovine tuberculosis outbreak in wildlife in
      France. We present a simple deterministic age-structured model of the within- and
      between-species M. bovis transmission in RD and WB populations that distinguishes
      direct transmission (horizontal and pseudo-vertical) and indirect transmission
      through contaminated offal left behind by hunters. Results issued from the
      epidemiological surveys conducted in Normandy forests were used to estimate
      transmission parameters. Because data for RD and WB populations were not
      available, population sizes at demographic equilibrium were estimated and used to
      run the model. We qualitatively tested different control measure scenarios with
      our model, considering different mortality rates and offal harvesting, to
      determine which ones affect the success of infection control. The most realistic
      control scenario would combine the total depopulation of RD and good compliance
      with offal harvesting, because the model suggests that infected offal left by
      hunters represents the main transmission source of M. bovis in the field.

PMID- 22958263
TI  - Constructing ecological networks: a tool to infer risk of transmission and
      dispersal of leishmaniasis.
AB  - We extend a recently developed method for constructing ecological networks to
      infer potential biotic interactions between species and to also include
      environmental factors, in particular land cover, thus permitting a simultaneous
      analysis of the interaction between environment and species distribution as well
      as inter-species interactions. We apply the method to the transmission and
      dispersal of leishmaniasis in Mexico. We find that the most important potential
      vectors and reservoirs can be classified into assemblages associated with
      different types of habitat. This in turn can be used to understand and map
      potential transmission risk, as well as to construct risk scenarios for the
      dispersal of disease from one geographical region to another.

PMID- 22958264
TI  - ERP correlates of dual mechanisms of control in the counting Stroop task.
AB  - Event-related brain potentials (ERPs) were used to examine the neural correlates
      of proactive and reactive cognitive control within the context of the Dual
      Mechanisms of Control theory. Individuals performed the counting Stroop task and
      the proportion of congruent and incongruent trials was varied across blocks. The
      Stroop effect was smaller in the mostly incongruent block than in the mostly
      congruent block. The ERP data revealed a double dissociation between the medial
      frontal negativity (MFN) and the medial posterior negativity (MPN), where the
      amplitude of the MFN was greater in the mostly incongruent block and the
      amplitude of the MPN was greater in the mostly congruent block. The ERP data also
      revealed slow wave activity that distinguished the mostly incongruent and mostly
      congruent blocks. These findings support the idea that different regions of the
      cingulate and anterior frontal cortex underpin proactive and reactive control.

PMID- 22958265
TI  - Expression of nuclear progesterone receptor and progesterone receptor membrane
      components 1 and 2 in the oviduct of cyclic and pregnant cows during the post
      ovulation period.
AB  - BACKGROUND: Progesterone (P4) may modulate oviductal functions to promote early
      embryo development in cattle. In addition to its nuclear receptor (PR), P4 may
      mediate its actions through P4 receptor membrane component 1 (PGRMC1) and its
      relative, PGRMC2. Two successive experiments were undertaken to characterise the
      expression of PR, PGRMC1 and PGRMC2 in the bovine oviduct during the post
      ovulation period, and to relate their expression to the presence of an embryo,
      the proximity of the CL and to the region of the oviduct. METHODS: In the first
      experiment (Exp. I), whole oviduct sections were collected from Holstein cows at
      Day 1.5, Day 4 and Day 5 post-ovulation (n = 2 cows per stage). The expression of
      PR, PGRMC1 and PGRMC2 was studied in the ampulla and isthmus by RT-PCR, western
      blot and immunohistochemistry. In Exp. II, oviduct epithelial cells were
      collected from cyclic and pregnant Charolais cows (n = 4 cows per status) at Day
      3.5 post-ovulation and mRNA expression of PR, PGRMC1 and PGRMC2 was examined in
      the ampulla and isthmus by real-time quantitative PCR. RESULTS: In Exp. I, PR,
      PGRMC1 and PGRMC2 were expressed in all oviduct samples. PGRMC1 was mainly
      localised in the luminal epithelium whereas PR and PGRMC2 were localised in the
      epithelium as well as in the muscle and stroma layers of the oviduct. The
      expression was primarily nuclear for PR, primarily cytoplasmic for PGRMC1 and
      both nuclear and cytoplasmic for PGRMC2. In Exp. II, mRNA levels for PR, PGRMC1
      and PGRMC2 were not affected by either the pregnancy status or the side relative
      to the CL. However, the expression of PR and PGRMC2 varied significantly with the
      region of the oviduct: PR was more highly expressed in the isthmus whereas PGRMC2
      was more highly expressed in the ampulla. CONCLUSIONS: This is the first evidence
      of PGRMC2 expression in the bovine oviduct. Our findings suggest that P4
      regulates the functions of the bovine oviduct in a region-specific manner and
      through both classical and non classical pathways during the post-ovulation
      period.

PMID- 22958266
TI  - Optometry-based general population survey of pupil ruff atrophy and ocular
      hypertension.
AB  - BACKGROUND: To evaluate and describe the pupil ruff changes and relationship to
      intraocular pressure, pseudoexfoliation syndrome and glaucoma status in an
      optometric population in New Zealand. DESIGN: Prospective cross-sectional survey
      of an optometric population. PARTICIPANTS: Six hundred and twenty subjects over
      50 years old routinely attending the participating optometry practices. Exclusion
      criteria included previous intraocular surgery, ophthalmic laser, uveitis, angle
      closure and secondary glaucoma. METHODS: Multicentre study involving 11 optometry
      practices in the Wellington region, New Zealand. The pupillary ruff and
      associated gonioscopy findings of study participants were graded based on the
      previously published Pupil Ruff Atrophy grading system. Parameters evaluated
      include pupillary ruff absence and abnormality, pseudoexfoliation material and
      trabecular meshwork pigmentation. MAIN OUTCOME MEASURES: Correlations between
      intereye Pupil Ruff Atrophy grading differences and inter-eye intraocular
      pressure and cup:disc ratio differences. RESULTS: Six hundred and twenty subjects
      were included, with a mean age of 62.2 +/- 9.1 years and mean intraocular
      pressure of 14.8 +/- 3.4 mmHg. Four hundred and fourteen (66.8%) had bilateral
      pupil ruff changes and 12 (1.5%) had pseudoexfoliation. Inter-eye intraocular
      pressure asymmetry was significantly correlated with amount of missing pupillary
      ruff (r = 0.111; P = 0.022) and trabecular meshwork pigmentation (r = 0.147; P =
      0.002). Inter-eye cup:disc ratio asymmetry was not correlated with any of the
      Pupil Ruff Atrophy grading parameters. CONCLUSIONS: Asymmetry of pupillary ruff
      absence and trabecular meshwork pigmentation was correlated with intraocular
      pressure asymmetry (but not with cup:disc ratio asymmetry) in a general
      optometric population setting in New Zealand.

PMID- 22958267
TI  - Outpatient vs. home-based pulmonary rehabilitation in COPD: a randomized
      controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of
      morbidity and mortality affecting a large number of individuals in both developed
      and developing countries and it represents a significant financial burden for
      patients, families and society. Pulmonary rehabilitation (PR) is a
      multidisciplinary program that integrates components of exercise training,
      education, nutritional support, psychological support and self-care, resulting in
      an improvement in dyspnea, fatigue and quality of life. Despite its proven
      effectiveness and the strong scientific recommendations for its routine use in
      the care of COPD, PR is generally underutilized and strategies for increasing
      access to PR are needed. Home-based self-monitored pulmonary rehabilitation is an
      alternative to outpatient rehabilitation. In the present study, patients with
      mild, moderate and severe COPD submitted to either an outpatient or at-home PR
      program for 12 weeks were analyzed. METHODS: Patients who fulfilled the inclusion
      criteria were randomized into three distinct groups: an outpatient group who
      performed all activities at the clinic, a home-based group who performed the
      activities at home and a control group. PR consisted of a combination of aerobic
      exercises and strengthening of upper and lower limbs 3 times a week for 12 weeks.
      RESULTS: There was a significant difference in the distance covered on the six
      minute walk test (p < 0.05) and BODE index (p < 0.001) in the outpatient and at
      home groups after participating in the rehabilitation program compared to
      baseline. CONCLUSION: A home-based self-monitoring pulmonary rehabilitation
      program is as effective as outpatient pulmonary rehabilitation and is a valid
      alternative for the management of patients with COPD.

PMID- 22958268
TI  - A high serum interleukin-12p40 level prior to Kasai surgery predict a favourable
      outcome in children with biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is a paediatric cholestatic disease
      characterized by a progressive fibro-inflammation of the biliary tree. Current
      treatment of choice is to establish good bile flow via the Kasai operation. AIMS:
      We aimed to identify outcome-predictive serum biomarkers in BA infant. METHODS:
      Thirty-three BA children recruited from 1986 to 2007 served as the baseline-study
      group. An additional 11 children recruited from 2008 to 2011 served as the
      validation group. Serum samples were collected immediately before and 6 months
      after the Kasai operation for the assessment of serum cytokines, including tumour
      necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta),
      interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-10, IL-12p40 and IL-12p70
      as the candidate biomarkers. RESULTS: Increased serum TGF-beta levels indicated a
      lower Knodell hepatitis activity index at Kasai operation. The serum TGF-beta
      levels declined after the operation. Serum IL-12p40 levels before the Kasai
      operation were higher in the subjects with a 3-month jaundice-free status than in
      others (P = 0.001). A serum pre-operative IL-12p40 level of 33 pg/ml was
      predictive of a 3-month jaundice-free status after surgery (positive predictive
      value=81.0%; negative predictive value=83.3%). This biomarker was also predictive
      of a better outcome, in terms of 3-year survival with native liver (risk ratio
      [RR = 4.00]; P < 0.001), and 3-year jaundice-free survival with native liver (RR
      = 12.00; P < 0.001). We confirmed the predictive power of a high pre-operative IL
      12p40 level on 3-month jaundice-free status in the validation group. CONCLUSIONS:
      The pre-operative IL-12p40 level was a good predictive biomarker of clinical
      outcome in children with BA undergoing the Kasai operation.

PMID- 22958269
TI  - Primary and secondary restorative proctocolectomy for familial adenomatous
      polyposis: complications and long-term bowel function.
AB  - AIM: The aim of the study was to evaluate intra-operative difficulties,
      complications and long-term bowel function in polyposis patients undergoing
      conversion of an ileorectal anastomosis to an ileoanal pouch, compared with
      patients with a primary ileoanal pouch operation. METHOD: A national register
      based retrospective study was performed with clinical follow-up and a
      questionnaire on long-term bowel function. RESULTS: There were 84 patients in the
      study: 59 (70%) had a primary pouch operation and in 25 (30%) a secondary pouch
      procedure was attempted. This was abandoned, in one case, leaving 24 patients who
      had a successful secondary restorative proctocolectomy. The median (range) follow
      up was 123 (0-359) months. There were no intra-operative difficulties in the 59
      primary operations, but intra-operative difficulties were reported in nine of 25
      secondary operations (P < 0.001). Complications within 1 month of surgery
      occurred in six of 59 primary operations and in none of 24 secondary operations
      (P < 0.001); and late surgical complications occurred in eight of 55 primary
      operations and in eight of 24 secondary operations (P = 0.13). The only
      difference in bowel function was a lower frequency of nocturnal defaecation after
      secondary pouch formation (P = 0.02). CONCLUSION: Reoperation with proctectomy
      after a previous ileorectal anastomosis and conversion to restorative
      proctocolectomy is feasible in polyposis patients, with morbidity and functional
      results similar to those seen after a primary pouch operation.

PMID- 22958270
TI  - Effects of volatile substance abuse on the respiratory system in adolescents.
AB  - AIM: Inhalant abuse is a prevalent and often overlooked form of substance abuse
      in adolescents. Chronic inhalant abuse can damage respiratory, cardiac, renal,
      hepatic, and neurologic systems. This study aims to determine the physiologic
      effects of inhaling solvents on the respiratory functions. METHODS: The general
      health status of the subjects was assessed by history taking, physical
      examination and a questionnaire which was designed to show the severity of
      respiratory symptoms. Spirometry, ventilation/perfusion scintigraphy, and high
      resolution computed tomography (HRCT) were performed to assess pulmonary
      functions and anatomy. RESULTS: Thirty-one male volatile substance abusers and 19
      control subjects were included in the study. The mean age of onset of inhalant
      use was 14.6 +/- 2.2 (9-18) years and duration of drug use was 3.7 +/- 1.7 years.
      The most common respiratory symptoms in volatile substance abusers were nasal
      congestion (45.2%), sputum (38.7%), exercise intolerance (32.3%) and cough
      (22.6%). Results of spirometric studies showed 12 (41.4%) subjects with low FVC
      values < 80% of predicted, indicative of restrictive ventilatory pattern in the
      study group. Although the difference was not statistically significant,
      restrictive ventilatory pattern was higher in the study group. There was no
      statistically significant correlation between restrictive ventilatory pattern and
      the age of onset/duration/frequency of inhalant abuse, respiratory symptoms and
      scintigraphic abnormalities. Subjects who had restrictive pattern in their
      pulmonary function tests were more likely to have abnormal findings at HRCT (p <
      0.01). CONCLUSION: This study has shown a positive correlation between volatile
      substance abuse and the development of restrictive ventilatory pattern, but more
      comprehensive studies are needed for more precise conclusions.

PMID- 22958271
TI  - Optical modelling of the possible origins of transient refractive changes in
      diabetic patients.
AB  - PURPOSE: To explore theoretically the ocular components that might be responsible
      for the transient refractive changes observed in the eyes of diabetic patients,
      particularly during intensive glycaemic control. METHODS: Paraxial ray tracing
      with a model eye having a lens with a single equivalent refractive index was used
      to determine the sensitivity of refraction to change in the values of each
      biometric component. The changes required to produce a refractive change of 0.50
      D were compared with the reliability of current instrumentation to measure each
      parameter. RESULTS: If transient shifts of 0.50 D or more were caused by changes
      in surface curvatures or separations, the latter would easily be detectable by
      available measurement techniques. The fact that such parameter changes have not
      been reliably detected in clinical studies supports the concept that changes in
      refractive index cause the refractive changes. The most probable site of such
      index changes is the lens, a change of about 0.003 in equivalent index being
      required to produce a 0.50 change in refractive error. CONCLUSION: This analysis
      supports the concept that transient changes in refraction in diabetics are due to
      changes in the lens. It is likely that changes in the gradients of refractive
      index lens within the lens, and in their associated contribution to the overall
      power of the lens, play the key role, rather than changes in surface powers.

PMID- 22958272
TI  - Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs.
AB  - Current guidelines recommend the use of inhaled corticosteroids (ICS) for
      suppression of airway inflammation in patients with asthma. Although it is well
      known that ICS cause dose-related adrenocortical suppression, it is less known
      that they can lead to iatrogenic Cushing's syndrome (CS). Fluticasone propionate
      (FP) is an ICS more potent than beclomethasone and budesonide. FP is metabolized
      as mediated by cytochrome P450 3A4 in the liver and the gut. Systemic bioactivity
      of FP can increase with the use of drugs that affect the cytochrome P450. Herein,
      we report the rapid development of iatrogenic CS in a patient receiving
      paroxetine and mirtazepine for 12 weeks in addition to inhaled FP.

PMID- 22958273
TI  - Frequency of pleural effusion in acute bronchiolitis and its effect on prognosis.
AB  - AIM: To analyze the frequency of pleural effusion and the effect on prognosis in
      children with acute bronchiolitis. METHODS: A total of 69 infants aged 1-24
      months with acute bronchiolitis were studied between September 2009 and December
      2010. All patients'age, sex, breastfeeding duration, exposure to smoking, history
      of using vitamin D, symptoms duration, physical examination and laboratory
      findings were recorded. Bronchiolitis score and predisposing factors that
      influence the disease process were determined. Thorax ultrasonography was carried
      out in all patients, who were evaluated on the 3rd and 7th day of the treatment.
      RESULTS: Mean age of patients (43 boys, 26 girls) was 11.97 +/- 0.69 months
      (median 11 months). Breastfeeding duration was 8.26 +/- 0.56 months (median 8
      months). According to bronchiolitis score, 52 patients (75.4%) had mild and
      moderate bronchiolitis and 17 (24.6%) had severe bronchiolitis; 34 patients
      (49.2%) had pleural effusion. There was no relation between pleural effusion and
      symptoms. Frequency of pleural effusion was significantly higher in patients with
      risk factors. CONCLUSIONS: This study demonstrated that most of the acute
      bronchiolitis cases in the infants studied were accompanied by pleural effusion.
      Pleural effusion in acute bronchiolitis had no effects on prognosis.

PMID- 22958274
TI  - Central NUCB2/Nesfatin-1-expressing neurones belong to the hypothalamic-brainstem
      circuitry activated by hypoglycaemia.
AB  - Nesfatin-1 is a recently identified 82 amino acid peptide shown to have an
      anorexigenic effect on rodents when administrered centrally and peripherally.
      Nesfatin-1 is expressed not only in neurones of various brain areas, including
      the hypothalamic and brainstem nuclei, but also in peripheral organs, such as the
      stomach and the pancreas. Nesfatinergic neurones were reported to participate in
      the regulation of satiety signals and in the responses to other stimuli,
      including restraint stress, abdominal surgery, and lipopolysaccharide-induced
      inflammation. The present study aimed to investigate whether NUCB2/nesfatin-1
      expressing neurones also take part in the central signalling activated in
      response to hypoglycaemia and therefore are involved in central glucose sensing.
      Using immunolabelling methods based on the detection of the neuronal activation
      marker c-Fos and of nesfatin-1, we showed that peripheral injection of insulin
      induced a strong activation of nesfatin-1-expressing neurones in the brain vagal
      regulatory nuclei, including the arcuate nucleus, paraventricular nucleus,
      lateral hypothalamic area, dorsal motor nucleus of the vagus (DMNX) and nucleus
      of the tractus solitarius. In response to intracellular glucopaenia induced by
      i.p. or i.c.v. 2-deoxyglucose injection, the c-Fos/nesfatin-1 colocalisations
      observed at the hypothalamic and brainstem levels were similar to those observed
      after insulin-induced hypoglycaemia. Moreover, using Fluorogold as a retrograde
      tracer, we showed that nesfatinergic preganglionic DMNX neurones activated by
      hypoglycaemia target the stomach and the pancreas. Taken together, these results
      suggest that a subpopulation of nesfatinergic neurones belongs to the central
      network activated by hypoglycaemia, and that nesfatin-1 participates in the
      triggering of physiological and hormonal counter-regulations observed in response
      to hypoglycaemia.

PMID- 22958275
TI  - Work-related health symptoms among compost facility workers: a cross-sectional
      study.
AB  - BACKGROUND: Industrial composting is a relatively new and expanding activity.
      Several studies indicate that compost workers are at risk to develop health
      symptoms. The aim of this study was to assess the prevalence of work-related
      health symptoms among compost workers compared with control subjects. METHODS: A
      questionnaire was distributed among 62 workers (31 exposed and 31 non-exposed
      workers). Data were analyzed using simple and multiple logistic regression
      analyses. RESULTS: Workers exposed to organic dust reported significantly more
      often respiratory, irritation (e.g., eyes, nose and throat), gastrointestinal,
      and skin symptoms than the non-exposed group. Moreover, all work-related symptoms
      were significantly more often reported by exposed than non-exposed workers. After
      adjustment for smoking status and age, the associations between exposure and
      respiratory, gastrointestinal, and skin symptoms remained statistically
      significant, in particular if these symptoms were work-related. CONCLUSIONS: This
      study confirms that workers at compost facilities are at risk to develop
      occupational health problems, most likely related to organic dust exposure.

PMID- 22958276
TI  - HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current
      issues.
AB  - BACKGROUND: Human papillomavirus (HPV) is well known as the major etiological
      agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is
      uncommon, but is increasing steadily in the community over the last few decades.
      However, it has undergone an exponential rise in the men who have sex with men
      (MSM) and HIV + groups. HIV + MSM in particular, have anal cancer incidences
      about three times that of the highest worldwide reported cervical cancer
      incidences. DISCUSSION: There has therefore traditionally been a lack of data
      from studies focused on heterosexual men and non-HIV + women. There is also less
      evidence reporting on the putative precursor lesion to anal cancer (AIN - anal
      intraepithelial neoplasia), when compared to cervical cancer and CIN (cervical
      intraepithelial neoplasia). This review summarises the available biological and
      epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and
      anal cancer amongst traditionally non-high risk groups. SUMMARY: There is strong
      evidence to conclude that high-grade AIN is a precursor to anal cancer, and some
      data on the progression of AIN to invasive cancer.

PMID- 22958277
TI  - The safe insertion of peripheral intravenous catheters: a mixed methods
      descriptive study of the availability of the equipment needed.
AB  - BACKGROUND: Intravenous cannulation is undertaken in a high proportion of
      hospitalised patients. Much international attention has been given to the use of
      care bundles to reduce the incidence of infection in these patients. However,
      less attention has been given to the systems required to ensure availability of
      the equipment needed to support these care bundles. Our objectives were to assess
      how reliably the equipment recommended for a peripheral intravenous care bundle
      was available for use, and to explore factors which contributed to its non
      availability. METHODS: We studied 350 peripheral cannula insertions in three NHS
      hospital organisations across the UK. Staff inserting cannulae were asked to
      report details of all equipment problems. Key staff were then interviewed to
      identify the causes of problems with equipment availability, using semi
      structured qualitative interviews and a standard coding frame. RESULTS: 47
      equipment problems were recorded during 46 of 350 cannulations, corresponding to
      a reliability of 87%, or 94% if problems with sharps disposal were excluded.
      Overall reliability was similar in all three organisations, but the types of
      problem varied. Interviews revealed a variety of causes including issues
      associated with purchasing policies, storage facilities, and lack of teamwork and
      communication in relation to reordering. The many human factors related to the
      supply chain were highlighted. Often staff had adopted work-arounds to deal with
      these problems. CONCLUSIONS: Overall, 87% of cannulations had the correct and
      functional equipment available. Different problems were identified in different
      organisations, suggesting that each had resolved some issues. Supply chain
      management principles may be useful to support best practice in care bundle
      delivery.

PMID- 22958278
TI  - Computational prediction of protein-protein complexes.
AB  - BACKGROUND: Protein-protein interactions form the core of several biological
      processes. With protein-protein interfaces being considered as drug targets,
      studies on their interactions and molecular mechanisms are gaining ground. As the
      number of protein complexes in databases is scarce as compared to a spectrum of
      independent protein molecules, computational approaches are being considered for
      speedier model derivation and assessment of a plausible complex. In this study, a
      good approach towards in silico generation of protein-protein heterocomplex and
      identification of the most probable complex among thousands of complexes thus
      generated is documented. This approach becomes even more useful in the event of
      little or no binding site information between the interacting protein molecules.
      FINDINGS: A plausible protein-protein hetero-complex was fished out from 10
      docked complexes which are a representative set of complexes obtained after
      clustering of 2000 generated complexes using protein-protein docking softwares.
      The interfacial area for this complex was predicted by two "hotspot" prediction
      programs employing different algorithms. Further, this complex had the lowest
      energy and most buried surface area of all the complexes with the same
      interfacial residues. CONCLUSIONS: For the generation of a plausible protein
      heterocomplex, various software tools were employed. Prominent are the protein
      protein docking methods, prediction of 'hotspots' which are the amino acid
      residues likely to be in an interface and measurement of buried surface area of
      the complexes. Consensus generated in their predictions lends credence to the use
      of the various softwares used.

PMID- 22958279
TI  - Cool-season annual pastures with clovers to supplement wintering beef cows
      nursing calves.
AB  - In December of 3 years, 87 beef cows with nursing calves (594 +/- 9.8 kg;
      calving season, September to November) at side were stratified by body condition
      score, body weight, cow age, and calf gender and divided randomly into 6 groups
      assigned to 1 of 6 cool-season annual pastures (0.45 ha/cow) that had been
      interseeded into a dormant common bermudagrass (Cynodon dactylon [L.]
      Pers.)/bahiagrass (Paspalum notatum Flugge) sod. Pastures contained 1 of the
      following 3 seeding mixtures (2 pastures/mixture): 1) wheat (Triticum aestivum
      L.) and ryegrass (Lolium multiflorum Lam., WRG), 2) wheat and ryegrass plus red
      clover (Trifolium pretense L., WRR), or 3) wheat and ryegrass plus white
      (Trifolium repens L.) and crimson clovers (Trifolium incarnatum L., WRW). All
      groups had ad libitum access to grass hay (12% crude protein; 58% total
      digestible nutrients). The second week in December, cow estrous cycles were
      synchronized and artificially inseminated. In late December, a bull was placed
      with each group for 60-d. Data were analyzed with an analysis of variance using a
      mixed model containing treatment as the fixed effect and year as the random
      effect. Body weight and condition scores did not differ (P >= 0.27) among cows
      between February and June. Calf birth weights or average daily gain did not
      differ (P >= 0.17) among treatments; however, calves grazing pastures with
      clovers did tend (P = 0.06) to weigh more than calves grazing grass only. Weaning
      weight per cow exposed to a bull was greater (P = 0.02) for WRR and WRW than WRG.
      Cows grazing winter-annual pastures containing clovers tended to wean more calf
      body weight per cow exposed to a bull than cows grazing the grass only pastures.

PMID- 22958280
TI  - Gender differences in recreational and transport cycling: a cross-sectional mixed
      methods comparison of cycling patterns, motivators, and constraints.
AB  - BACKGROUND: Gender differences in cycling are well-documented. However, most
      analyses of gender differences make broad comparisons, with few studies modeling
      male and female cycling patterns separately for recreational and transport
      cycling. This modeling is important, in order to improve our efforts to promote
      cycling to women and men in countries like Australia with low rates of transport
      cycling. The main aim of this study was to examine gender differences in cycling
      patterns and in motivators and constraints to cycling, separately for
      recreational and transport cycling. METHODS: Adult members of a Queensland,
      Australia, community bicycling organization completed an online survey about
      their cycling patterns; cycling purposes; and personal, social and perceived
      environmental motivators and constraints (47% response rate). Closed and open-end
      questions were completed. Using the quantitative data, multivariable linear,
      logistic and ordinal regression models were used to examine associations between
      gender and cycling patterns, motivators and constraints. The qualitative data
      were thematically analyzed to expand upon the quantitative findings. RESULTS: In
      this sample of 1862 bicyclists, men were more likely than women to cycle for
      recreation and for transport, and they cycled for longer. Most transport cycling
      was for commuting, with men more likely than women to commute by bicycle. Men
      were more likely to cycle on-road, and women off-road. However, most men and
      women did not prefer to cycle on-road without designed bicycle lanes, and
      qualitative data indicated a strong preference by men and women for bicycle-only
      off-road paths. Both genders reported personal factors (health and enjoyment
      related) as motivators for cycling, although women were more likely to agree that
      other personal, social and environmental factors were also motivating. The main
      constraints for both genders and both cycling purposes were perceived
      environmental factors related to traffic conditions, motorist aggression and
      safety. Women, however, reported more constraints, and were more likely to report
      as constraints other environmental factors and personal factors. CONCLUSION:
      Differences found in men's and women's cycling patterns, motivators and
      constraints should be considered in efforts to promote cycling, particularly in
      efforts to increase cycling for transport.

PMID- 22958283
TI  - Intrathoracic splenosis presenting as persistent chest pain.
AB  - Thoracic splenosis is a rare entity resulting from splenic and diaphragmatic
      injury. Patients remain asymptomatic, and surgical intervention is not indicated
      in the majority of cases. We report a case of a 50-year-old male with a history
      of splenectomy due to a gunshot wound 30 years previously who presented with
      vague, progressively worsening chest pain. He was found to have a large
      intrathoracic splenosis. Unique features of our patient include the presence of
      symptoms, the significant interval growth of the splenic tissue, and the
      unprecedented size of the mass, which we believe to be the largest among those
      previously described.

PMID- 22958282
TI  - Of mice and monkeys: using non-human primate models to bridge mouse- and human
      based investigations of autism spectrum disorders.
AB  - The autism spectrum disorders (ASDs) arise from a diverse array of genetic and
      environmental origins that disrupt the typical developmental trajectory of neural
      connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior
      and cognition, among other deficits. Greater understanding of the biological
      substrates of typical social behavior in animal models will further our
      understanding of the etiology of ASDs. Despite the precision and tractability of
      molecular genetics models of ASDs in rodents, these organisms lack the complexity
      of human social behavior, thus limiting their impact on understanding ASDs to
      basic mechanisms. Non-human primates (NHPs) provide an attractive, complementary
      model for ASDs, due in part to the complexity and dynamics of social structures,
      reliance on vision for social signaling, and deep homology in brain circuitry
      mediating social behavior and reward. This knowledge is based on a rich
      literature, compiled over 50 years of observing primate behavior in the wild,
      which, in the case of rhesus macaques, is complemented by a large body of
      research characterizing neuronal activity during cognitive behavior. Several
      recent developments in this field are directly relevant to ASDs, including how
      the brain represents the perceptual features of social stimuli, how social
      information influences attention processes in the brain, and how the value of
      social interaction is computed. Because the symptoms of ASDs may represent
      extreme manifestations of traits that vary in intensity within the general
      population, we will additionally discuss ways in which nonhuman primates also
      show variation in social behavior and reward sensitivity. In cases where
      variation in species-typical behavior is analogous to similar variations in human
      behavior, we believe that study of the neural circuitry underlying this variation
      will provide important insights into the systems-level mechanisms contributing to
      ASD pathology.

PMID- 22958281
TI  - Ecology of zoonotic infectious diseases in bats: current knowledge and future
      directions.
AB  - Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human
      activities that increase exposure to bats will likely increase the opportunity
      for infections to spill over in the future. Ecological drivers of pathogen
      spillover and emergence in novel hosts, including humans, involve a complex
      mixture of processes, and understanding these complexities may aid in predicting
      spillover. In particular, only once the pathogen and host ecologies are known can
      the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary
      approaches are required to understand how host and pathogen ecology interact.
      Bats differ from other sylvatic disease reservoirs because of their unique and
      diverse lifestyles, including their ability to fly, often highly gregarious
      social structures, long lifespans and low fecundity rates. We highlight how these
      traits may affect infection dynamics and how both host and pathogen traits may
      interact to affect infection dynamics. We identify key questions relating to the
      ecology of infectious diseases in bats and propose that a combination of field
      and laboratory studies are needed to create data-driven mechanistic models to
      elucidate those aspects of bat ecology that are most critical to the dynamics of
      emerging bat viruses. If commonalities can be found, then predicting the dynamics
      of newly emerging diseases may be possible. This modelling approach will be
      particularly important in scenarios when population surveillance data are
      unavailable and when it is unclear which aspects of host ecology are driving
      infection dynamics.

PMID- 22958284
TI  - Age-related prevalence of Methanomassiliicoccus luminyensis in the human gut
      microbiome.
AB  - A 16S rDNA sequence-based investigation of methanogenic Archaea in the human
      stools found Methanobrevibacter smithii in 99.2% and Methanosphaera stadtmanae in
      32.6%. The recently described Methanomassiliicoccus luminyensis found by others
      to be representative of a new order of methanogenic Archaea was found in 4% of
      stool specimens. The prevalence of M. luminyensis significantly increased with
      age, contrary to M. smithii and M. stadtmanae.

PMID- 22958285
TI  - Antibiotic susceptibility in prostate-derived Propionibacterium acnes isolates.
AB  - The aim of this study was to determine antibiotic susceptibility of
      Propionibacterium acnes isolates from prostate. Prostate-derived P. acnes
      isolates (n = 24, Umea & Orebro, Sweden, 2007-2010) and a panel of control
      strains (n = 25, Sweden) collected from skin and deep infections were assessed
      for resistance to penicillin G, piperacillin-tazobactam, imipenem, gentamicin,
      azithromycin, erythromycin, vancomycin, ciprofloxacin, moxifloxacin,
      tetracycline, tigecycline, fusidic acid, clindamycin, rifampicin, linezolid,
      daptomycin, trimethoprim-sulfamethoxazole, and metronidazole. In addition, the
      isolates were tested for inducible clindamycin resistance. All prostate derived
      P. acnes isolates displayed wild-type distribution of MIC-values, without
      evidence of acquired resistance. In the reference panel, 5 of 25 isolates had
      acquired macrolide resistance with cross-resistance to azithromycin, clindamycin,
      and erythromycin. In addition, one of these isolates was resistant to
      tetracycline.

PMID- 22958286
TI  - Protective immunization against Staphylococcus aureus infection in a novel
      experimental wound model in mice.
AB  - A novel murine experimental wound infection model was used to assess the efficacy
      of multi-component immunization against Staphylococcus aureus infection. Necrotic
      lesions were induced in mice with venom from Bothrops asper and infected with a
      low inoculum, 1 * 10(2) CFU. The wound infection model therefore more resembles a
      clinical case of S. aureus infection compared with conventional infection models
      where far more bacteria are required. Before infection, mice were immunized with
      four recombinant S.aureus proteins expressed from Escherichia coli: (i) domains 1
      3 of Extracellular adherence protein (Eap), (ii) Efb - D (fusion protein
      combining Extracellular fibrinogen binding protein (Efb) and a fibronectin
      binding domain (D) of the fibronectin binding protein (FnBP) and (iii) clumping
      factor A (ClfA). In the immunized group, lower bacterial colonization,
      undisturbed crust formation and significantly faster wound healing were found
      compared with the unimmunized control group. Efb and Eap have previously been
      found to impair wound healing and neutralization of these proteins by antibodies
      restores a more natural wound healing process. This effect is further also
      enhanced by the proposed opsonic activity of antibodies against ClfA and FnBP.

PMID- 22958287
TI  - Biofilm formation in long-term central venous catheters in children with cancer:
      a randomized controlled open-labelled trial of taurolidine versus heparin.
AB  - Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of
      this study was to compare the effect of catheter locking with taurolidine vs
      heparin in biofilm formation in central venous catheters. Forty-eight children
      with cancer were randomized to catheter locking by heparin (n = 22) or
      taurolidine (n = 26), respectively. After removal, catheters were examined by
      standardized scanning electron microscopy to assess quantitative biofilm
      formation. Biofilm was present if morphologically typical structures and
      bacterial cells were identified. Quantitative and semi-quantitative cultures were
      also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine
      group and 21 of 22 catheters from the heparin group. A positive culture was made
      of six of the catheters locked with taurolidine and heparin, respectively (p =
      0.78). The rate of catheter-related bloodstream infections (CRBSI) was 0.1 per
      1000 catheter-days using taurolidine and 0.9 per 1000 catheter-days using heparin
      (p = 0.03). This randomized trial confirmed that the use of taurolidine as
      catheter-lock compared with heparin reduced the rate of CRBSIs; this reduction
      was not related to a reduction in the intraluminal biofilm formation and the rate
      of bacterial colonization detected by scanning electron microscopy in the two
      groups.

PMID- 22958288
TI  - Occurrence of potentially pathogenic bacteria on the hands of hospital patients
      before and after the introduction of patient hand disinfection.
AB  - The leading cause of nosocomial infections and spread of multiresistant bacteria
      is considered to be the failure of healthcare workers to perform appropriate hand
      hygiene. The role of the hands of hospital patients in the spread of infection
      has received little attention. The aim of the present study was to investigate
      the occurrence of potentially pathogenic bacteria on the patients' hands.
      Quantitative cultures were repeatedly taken from the fingertips of patients at a
      rehabilitation clinic before and after an intervention in which patient hand
      disinfection was introduced and promoted. Before the intervention, the occurrence
      on the hands of Escherichia coli, Klebsiella spp., enterococci, Staphylococcus
      aureus and yeast was a common finding. The colony counts of S. aureus were often
      higher than the counts of other organisms. After the intervention, the level of
      hand contamination was lower. The difference was statistically significant (p <
      0.05) concerning Enterobacteriaceae, both when the patients were resting and at
      lunch time, for enterococci and total bacterial counts at lunch time, and for
      yeast when they were resting. Concerning S. aureus, the difference was not
      statistically significant, neither while resting nor at lunch time. The role of
      the patients in the spread of pathogenic bacteria merits more discussion.

PMID- 22958289
TI  - Modulation of FLT3 signaling targets conventional dendritic cells to attenuate
      acute lung injury.
AB  - Conventional dendritic cells (cDCs) have been reported to participate in the
      pathophysiology of acute lung injury (ALI). Fms-like tyrosine kinase 3 (FLT3)
      signaling represents a highly specific pathway for the manipulation of cDCs in
      vivo. The purpose of this study was to clarify the effect of FLT3 signaling on
      the accumulation and maturation of pulmonary cDCs, and whether inhibition of FLT3
      signaling may attenuate acute lung inflammation and lung injury. C57BL/6 mice
      were pretreated with FLT3-ligand (FLT3L) and lestaurtinib separately for five
      consecutive days. A murine model of ALI was subsequently generated by intra
      tracheal instillation of lipopolysaccharide (LPS) and lung specimens were
      harvested 24 h later. Flow cytometry was conducted to measure the accumulation
      and maturation of pulmonary cDCs. IL-6, IFN-gamma, IL-4, MPO activity and
      transcription factor T-bet/GATA-3 mRNA ratio were quantified to evaluate lung
      inflammation. Lung injury was estimated by lung wet weight/body weight ratio
      (LWW/BW) and histopathological analysis. LPS challenge resulted in rapid
      accumulation and maturation of pulmonary cDCs. FLT3L pretreatment further
      stimulated the accumulation and maturation of pulmonary cDCs, leading to a
      markedly increased LWW/BW and aggravated lung histopathology. Meanwhile, lung MPO
      activity, T-bet/GATA-3 mRNA ratio and concentrations of IL-6 and IFN-gamma were
      elevated by FLT3L administration. In contrast, lestaurtinib pretreatment
      inhibited the accumulation and maturation of pulmonary cDCs, leading to a
      significantly decreased LWW/BW and improved lung histopathology. Lestaurtinib
      administration also suppressed lung MPO activity, T-bet/GATA-3 mRNA ratio and
      production of IL-6 and IFN-gamma. Our findings show that FLT3 signaling
      ameliorates ALI by regulating the accumulation and maturation of pulmonary cDCs,
      suggesting an innovative pharmacotherapy for ALI.

PMID- 22958290
TI  - Limitations of tissue micro array in Duke's B colon cancer.
AB  - Tissue micro array (TMA) is widely used in cancer research in search of new
      predictive and prognostic markers. Colon cancer is known to be heterogeneous and
      the present study addresses some methodological aspects using cores of different
      size and analysing markers with different cellular distribution. We selected 61
      paraffin-embedded tissue blocks representing patients diagnosed with Dukes B
      colon cancer. Two 1 mm and two 2 mm cores were taken from both the centre and the
      invasive front of the tumour respectively. The immunostaining included MLH1,
      MSH2, PMS2, p53, COX-2, TIMP and Betacatenin. Twenty-five percent of the cores
      taken from paraffin blocks less than 0.5 cm was lost and the total loss was 8%.
      The homogeneous stains (MLH1, MSH2 and PMS2) all showed high agreement between
      TMA and whole tissue stains (kappa = 0.96,1 and 1 respectively). The COX-2, p53
      and Betacatenin illustrated moderate to high agreement (kappa = 0.54-0.9) whereas
      TIMP-1 had the lowest score (kappa 0.19-0.25). The application of TMA in Dukes B
      colon cancer has several pitfalls and depends substantially on the
      immunohistochemical marker in question. Therefore a validation study seems
      justified before applying large scale TMA in this setting.

PMID- 22958291
TI  - Human leukocyte antigen-C and killer cell immunoglobulin-like receptor gene
      polymorphisms among patients with syphilis in a Chinese Han population.
AB  - Syphilis is a sexually transmitted infection caused by the Treponema pallidum
      subspecies pallidum spirochete bacterium. The killer cell immunoglobulin-like
      receptors (KIR), interacting with human leukocyte antigens (HLA), regulate the
      activations of natural killer (NK) cells and certain T-cell subsets in response
      to microbe infection. The objective of this study was to explore whether KIR and
      HLA-C gene polymorphisms were associated with syphilis in a Chinese Han
      population. Polymerase chain reaction with sequence-specific primers (PCR-SSP)
      method was used to genotype KIR and HLA-C genes in 231 syphilis patients and 247
      healthy controls. Framework genes KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were
      present in all individuals. The frequencies of KIR2DS3 and KIR3DS1 were higher in
      syphilis patients than in healthy controls (p = 0.030 and p = 0.038,
      respectively), while the frequency of KIR2DS5 was higher in healthy controls than
      in syphilis patients (p = 0.015; OR = 0.575). The homozygote for HLA-C1 allele
      (HLA-C1C1) was more common in controls compared with syphilis patients (p =
      0.030; OR = 0.667). The frequency of individuals with HLA-C1C1 and KIR2DL3
      genotype was higher in control group relative to syphilis patient group (p =
      0.018; OR = 0.647). These data indicated that KIR2DS3 and KIR3DS1 were more
      prevalent in syphilis patients than in controls, and that KIR2DS5, HLA-C1C1 and
      HLA-C1C1-KIR2DL3 were more prevalent in controls than in syphilis patients,
      respectively. These will require further investigation using functional studies.

PMID- 22958292
TI  - Anti-leukemic effect of a synthetic compound, (+/-) trans-dihydronarciclasine
      (HYU-01) via cell-cycle arrest and apoptosis in acute myeloid leukemia.
AB  - (+/-) trans-Dihydronarciclasine, isolated from Chinese medicinal plant
      Zephyranthes candida, has been shown to possess quite potent anti-tumoral effect
      against selected human cancer cell lines. However, little is known about the anti
      tumoral effect of (+/-) trans-dihydronarciclasine in acute myeloid leukemia
      (AML). This study was performed to investigate the effect of a novel synthetic
      (+/-) trans-dihydronarciclasine (code name; HYU-01) in AML. The HYU-01 inhibited
      the proliferation of various AML cell lines including HL-60 as well as primary
      leukemic blasts in a dose-dependent manner. To investigate the mechanism of the
      anti-proliferative effect of HYU-01, cell-cycle analysis was attempted in HL-60
      cells, resulting in G1 arrest. The expression levels of CDK2, CDK4, CDK6, cyclin
      E, and cyclin A were decreased in a time-dependent manner. In addition, HYU-01 up
      regulated the expression of the p27, and markedly enhanced the binding of p27
      with CDK2, 4, and 6, ultimately resulting in the decrease of their kinase
      activities. Furthermore, HYU-01 induced the apoptosis through the induction of
      proapoptotic molecules and reduction of antiapoptotic molecules in association
      with the activation of caspase-3, -8, and -9. These results suggest that HYU-01
      may inhibit the proliferation of HL-60 cells, via apoptosis, as well as G1 block
      in association with the induction of p27.

PMID- 22958293
TI  - Limited prognostic value of tissue protein expression levels of cyclin E in
      Danish ovarian cancer patients: from the Danish 'MALOVA' ovarian cancer study.
AB  - The primary objective of this study was to assess the expression of cyclin E in
      tumour tissues from 661 patients with epithelial ovarian tumours. The second was
      to evaluate whether cyclin E tissue expression levels correlate with clinico
      pathological parameters and prognosis of the disease. Using tissue arrays (TA),
      we analysed the cyclin E expression levels in tissues from 168 women with
      borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493
      Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage
      IV). Using a 10% cut-off level for cyclin E overexpression, 20% of the BOTs were
      positive with a higher proportion of serous than mucinous tumours. Sixty-two per
      cent of the OCs were positive for cyclin E expression with the highest percentage
      found in clear cell carcinomas. Results based on univariate and multivariate
      survival analyses with a 10% cut-off value showed that cyclin E had no
      independent prognostic value. In conclusion, we found cyclin E expression in
      tumour tissue to be of limited prognostic value to Danish OC patients.

PMID- 22958294
TI  - Somatic mutation of a tumor suppressor gene BAP1 is rare in breast, prostate,
      gastric and colorectal cancers.

PMID- 22958295
TI  - Understanding and using comparative healthcare information; the effect of the
      amount of information and consumer characteristics and skills.
AB  - BACKGROUND: Consumers are increasingly exposed to comparative healthcare
      information (information about the quality of different healthcare providers).
      Partly because of its complexity, the use of this information has been limited.
      The objective of this study was to examine how the amount of presented
      information influences the comprehension and use of comparative healthcare
      information when important consumer characteristics and skills are taken into
      account. METHODS: In this randomized controlled experiment, comparative
      information on total hip or knee surgery was used as a test case. An online
      survey was distributed among 800 members of the NIVEL Insurants Panel and 76 hip-
      or knee surgery patients. Participants were assigned to one of four subgroups,
      who were shown 3, 7, 11 or 15 quality aspects of three hospitals. We conducted
      Kruskall-Wallis tests, Chi-square tests and hierarchical multiple linear
      regression analyses to examine relationships between the amount of information
      and consumer characteristics and skills (literacy, numeracy, active choice
      behaviour) on one hand, and outcome measures related to effectively using
      information (comprehension, perceived usefulness of information, hospital choice,
      ease of making a choice) on the other hand. RESULTS: 414 people (47%)
      participated. Regression analysis showed that the amount of information slightly
      influenced the comprehension and the perceived usefulness of comparative
      healthcare information. It did not affect consumers' hospital choice and ease of
      making this choice. Consumer characteristics (especially age) and skills
      (especially literacy) were the most important factors affecting the comprehension
      of information and the ease of making a hospital choice. For the perceived
      usefulness of comparative information, active choice behaviour was the most
      influencing factor. CONCLUSION: The effects of the amount of information were not
      unambiguous. It remains unclear what the ideal amount of quality information to
      be presented would be. Reducing the amount of information will probably not
      automatically result in more effective use of comparative healthcare information
      by consumers. More important, consumer characteristics and skills appeared to be
      more influential factors contributing to information comprehension and use.
      Consequently, we would suggest that more emphasis on improving consumers' skills
      is needed to enhance the use of comparative healthcare information.

PMID- 22958296
TI  - Antimicrobial stewardship in Scotland: impact of a national programme.
AB  - BACKGROUND: The Scottish Antimicrobial Prescribing Group (SAPG) was established
      by the Scottish Government in 2008 to lead the first national initiative to
      actively address antimicrobial stewardship. Healthcare associated infection (HAI)
      is a priority in Scotland and the work of SAPG contributes to the national HAI
      Delivery Plan. SAPG's early work has focused on restricting the use of
      antibiotics associated with a high risk of Clostridium difficile infection (CDI)
      and development of national prescribing indicators to support reduction of CDI.
      FINDINGS: Scottish Antimicrobial Prescribing Group has developed prescribing
      indicators for hospital and primary care, which are measured and reported in all
      14 NHS board areas. Improvement in compliance with the indicators has been
      demonstrated with resultant reductions in CDI rates and no adverse effect on
      mortality or antimicrobial resistance patterns. CONCLUSIONS: The establishment of
      a Scottish national antimicrobial stewardship programme has made a significant
      contribution to the HAI agenda, particularly in relation to CDI. The programme is
      supported by local antimicrobial teams, a national framework for education,
      surveillance of antimicrobial use and resistance and sharing of data for
      improvement. Antimicrobial stewardship has been integrated with other national
      programmes on patient safety and quality improvement.

PMID- 22958298
TI  - Burden of illness and treatment patterns for patients with fibromyalgia.
AB  - OBJECTIVE:   This study was designed to describe burden of illness and treatment
      patterns, and to examine the patient, physician, and care factors associated with
      the treatment choices of individuals receiving new prescriptions for fibromyalgia
      (FM). DESIGN:   This is a baseline assessment of the Real-World Examination of
      Fibromyalgia: Longitudinal Evaluation of Costs and Treatments (REFLECTIONS), a
      prospective observational study. Baseline data (including a physician survey, a
      patient visit form, and computer-assisted telephone interviews) were collected
      from July 2008 through May 2010 in 58 care settings in the United States,
      including Puerto Rico. RESULTS:   Patients (N = 1,700) were mostly female (94.6%)
      and white (82.9%). Mean age was 50.4 years and mean duration of illness was 5.6
      years. Mean Fibromyalgia Impact Questionnaire total score was 54.4 (range 0-80),
      and Brief Pain Inventory average pain severity level was 5.5 (range 0-10).
      Patients reported high annual health care use and numerous work limitations
      related to FM. Patients were taking 182 unique types of medications prescribed
      for FM, including duloxetine (26.8%), nonsteroidal anti-inflammatory drugs
      (26.6%), pregabalin (24.5%), opioids (24.2%), tramadol (15.3%), benzodiazepines
      (15.2%), cyclobenzaprine (12.9%), milnacipran (8.9%), and others. Most patients
      took more than one medication concurrently (77.8%). Type of current medications
      used was most strongly associated with medication history and physician
      specialty. CONCLUSIONS:   Burden of illness was high for patients with FM, and
      treatment patterns were highly variable. Importantly, the treatments with the
      most evidence to support their use were not always the most frequently chosen.

PMID- 22958300
TI  - Multiplanar and two-dimensional imaging of central airway stenting with
      multidetector computed tomography.
AB  - BACKGROUND: Multidetector computed tomography (MDCT) provides guidance for
      primary screening of the central airways. The aim of our study was assessing the
      contribution of multidetector computed tomography- two dimensional reconstruction
      in the management of patients with tracheobronchial stenosis prior to the
      procedure and during a short follow up period of 3 months after the endobronchial
      treatment. METHODS: This is a retrospective study with data collected from an
      electronic database and from the medical records. Patients evaluated with MDCT
      and who had undergone a stenting procedure were included. A Philips RSGDT 07605
      model MDCT was used, and slice thickness, 3 mm; overlap, 1.5 mm; matrix, 512x512;
      mass, 90 and kV, 120 were evaluated. The diameters of the airways 10 mm proximal
      and 10 mm distal to the obstruction were measured and the stent diameter (D) was
      determined from the average between D upper and D lower. RESULTS: Fifty-six
      patients, 14 (25%) women and 42 (75%) men, mean age 55.3 +/- 13.2 years (range:
      16-79 years), were assessed by MDCT and then treated with placement of an
      endobronchial stent. A computed tomography review was made with 6 detector
      Philips RSGDT 07605 multidetector computed tomography device. Endobronchial
      therapy was provided for the patients with endoluminal lesions. Stents were
      placed into the area of stenosis in patients with external compression after
      dilatation and debulking procedures had been carried out. In one patient the
      migration of a stent was detected during the follow up period by using MDCT.
      CONCLUSIONS: MDCT helps to define stent size, length and type in patients who are
      suitable for endobronchial stinting. This is a non-invasive, reliable method that
      helps decisions about optimal stent size and position, thus reducing
      complications.

PMID- 22958299
TI  - Integrating cytogenetics and genomics in comparative evolutionary studies of
      cichlid fish.
AB  - BACKGROUND: The availability of a large number of recently sequenced vertebrate
      genomes opens new avenues to integrate cytogenetics and genomics in comparative
      and evolutionary studies. Cytogenetic mapping can offer alternative means to
      identify conserved synteny shared by distinct genomes and also to define genome
      regions that are still not fine characterized even after wide-ranging nucleotide
      sequence efforts. An efficient way to perform comparative cytogenetic mapping is
      based on BAC clones mapping by fluorescence in situ hybridization. In this
      report, to address the knowledge gap on the genome evolution in cichlid fishes,
      BAC clones of an Oreochromis niloticus library covering the linkage groups (LG)
      1, 3, 5, and 7 were mapped onto the chromosomes of 9 African cichlid species. The
      cytogenetic mapping data were also integrated with BAC-end sequences information
      of O. niloticus and comparatively analyzed against the genome of other fish
      species and vertebrates. RESULTS: The location of BACs from LG1, 3, 5, and 7
      revealed a strong chromosomal conservation among the analyzed cichlid species
      genomes, which evidenced a synteny of the markers of each LG. Comparative in
      silico analysis also identified large genomic blocks that were conserved in
      distantly related fish groups and also in other vertebrates. CONCLUSIONS:
      Although it has been suggested that fishes contain plastic genomes with high
      rates of chromosomal rearrangements and probably low rates of synteny
      conservation, our results evidence that large syntenic chromosome segments have
      been maintained conserved during evolution, at least for the considered markers.
      Additionally, our current cytogenetic mapping efforts integrated with genomic
      approaches conduct to a new perspective to address important questions involving
      chromosome evolution in fishes.

PMID- 22958301
TI  - Fatigue and multidimensional disease severity in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND AND AIMS: Fatigue is associated with longitudinal ratings of health in
      patients with chronic obstructive pulmonary disease (COPD). Although the degree
      of airflow obstruction is often used to grade disease severity in patients with
      COPD, multidimensional grading systems have recently been developed. The aim of
      this study was to investigate the relationship between perceived and actual
      fatigue level and multidimensional disease severity in patients with COPD.
      MATERIALS AND METHODS: Twenty-two patients with COPD (aged 52-74 years) took part
      in the study. Multidimensional disease severity was measured using the SAFE and
      BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale
      (FSS) and the Fatigue Impact Scale (FIS). Peripheral muscle endurance was
      evaluated using the number of sit-ups, squats, and modified push-ups that each
      patient could do. RESULTS: Thirteen patients (59%) had severe fatigue, and their
      St George's Respiratory Questionnaire scores were significantly higher (p <
      0.05). The SAFE index score was significantly correlated with the number of sit
      ups, number of squats, FSS score and FIS score (p < 0.05). The BODE index was
      significantly associated with the numbers of sit-ups, squats and modified push
      ups, and with the FSS and FIS scores (p < 0.05). CONCLUSIONS: Peripheral muscle
      endurance and fatigue perception in patients with COPD was related to
      multidimensional disease severity measured with both the SAFE and BODE indices.
      Improvements in perceived and actual fatigue levels may positively affect
      multidimensional disease severity and health status in COPD patients. Further
      research is needed to investigate the effects of fatigue perception and exercise
      training on patients with different stages of multidimensional COPD severity.

PMID- 22958302
TI  - Cervical necrotizing fasciitis associated with descending necrotizing
      mediastinitis.
AB  - We report a case of potentially fatal cervical necrotizing fasciitis and
      descending necrotizing mediastinitis due to deep neck infection in a 66-year-old
      male patient with no history or evidence of immunocompromising disorders. On
      admission, he had painful neck movements and the skin over his neck was red, hot
      and tender. A computerized tomography (CT) scan of his neck and chest showed
      evidence of air collection in soft tissues. He was treated with broad-spectrum
      intravenous antibiotics and early massive cervical drainage. Prompt diagnosis by
      CT of the neck and chest enabled an early surgical treatment of cervical
      necrotizing fasciitis. Although acute mediastinitis is a fatal infection
      involving the connective tissues that fill the interpleural spaces and surround
      the median thoracic organs, an extensive cervicotomy combined with appropriate
      antibiotics can prevent the need for mediastinal drainage.

PMID- 22958304
TI  - Round atelectasis in sarcoidosis.
AB  - Round atelectasis is a benign inflammatory condition most frequently observed in
      patients with asbestos exposure but it can also result from a variety of chronic
      pleural diseases like infection. It has not previously been described in
      sarcoidosis. We report the occurrence of round atelectasis in four previously
      diagnosed sarcoidosis patients who were under follow up at our outpatient clinic.
      Three patients had symptoms consisting of thoracic pain, dry cough and sensation
      of fullness at the posterior thorax, respectively. Chest roentgenogram showed
      subpleural or pleural based opacity with diameters ranging from 2 to 3 cm in each
      of the patients. Chest computerized tomography (CT) revealed features of round
      atelectasis. Fiberoptic bronchoscopy with transbronchial lung biopsy was
      performed. Diagnosis was confirmed by the histopathologic examination of the
      biopsy samples. The mechanical influence of a prior pleural effusion due to
      sarcoidosis may be the predominant mechanism underlying the onset of round
      atelectasis in these patients. Clinicians should bear in mind the possibility of
      sarcoidosis as an etiologic factor for round atelectasis.

PMID- 22958305
TI  - Validation of CRP as prognostic marker for renal cell carcinoma in a large series
      of patients.
AB  - BACKGROUND: To evaluate the prognostic significance of the pre-operative C
      reactive protein (CRP) serum level in patients with renal cell cancer (RCC).
      METHODS: We evaluated 1,161 RCC patients with complete patient and tumour
      specific characteristics as well as information about their pre-operative CRP
      level, who had undergone either radical nephrectomy or nephron-sparing surgery at
      two German high-volume centres (University Hospitals of Hannover and Ulm). The
      mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three
      subgroups (CRP <= 4, 4-10, and >10 mg/l), correlated significantly with tumour
      stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and
      distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year
      cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p
      < 0.001). Multivariate analysis identified CRP as an independent prognosticator
      for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4-10 and
      >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared
      to those with a pre-operative CRP <=4 mg/l, respectively. CONCLUSIONS: A high
      preoperative serum CRP level is an independent predictor of poor survival in
      patients with RCC. Its routine use could allow better risk stratification and
      risk-adjusted follow-up of RCC patients.

PMID- 22958303
TI  - Social opportunity causes rapid transcriptional changes in the social behaviour
      network of the brain in an African cichlid fish.
AB  - Animals constantly integrate external stimuli with their own internal
      physiological state to make appropriate behavioural decisions. Little is known,
      however, about where in the brain the salience of these signals is evaluated, or
      which neural and transcriptional mechanisms link this integration to adaptive
      behaviours. We used an African cichlid fish Astatotilapia burtoni to test the
      hypothesis that a new social opportunity activates the conserved 'social
      behaviour network' (SBN), a collection of brain nuclei known to regulate social
      behaviours across vertebrates. We measured mRNA levels of immediate early genes
      (IEGs) in microdissected brain regions as a proxy for neuronal activation, and
      discovered that IEGs were higher in all SBN nuclei in males that were given an
      opportunity to rise in social rank compared to control stable subordinate and
      dominant individuals. Furthermore, because the presence of sex-steroid receptors
      is one defining criteria of SBN nuclei, we also tested whether social opportunity
      or status influenced androgen and oestrogen receptor mRNA levels within these
      same regions. There were several rapid region-specific changes in receptor mRNA
      levels induced by social opportunity, most notably in oestrogen receptor subtypes
      in areas that regulate social aggression and reproduction, suggesting that
      oestrogenic signalling pathways play an important role in regulating male status.
      Several receptor mRNA changes occurred in regions with putative homologies to the
      mammalian septum and extended amygdala, two regions shared by SBN and reward
      circuits, suggesting an important role in the integration of social salience,
      stressors, hormonal state and adaptive behaviours. We also demonstrated increases
      in plasma sex- and stress-steroids at 30 min after a rise in social rank. This
      rapid endocrine and transcriptional response suggests that the SBN is involved in
      the integration of social inputs with internal hormonal state to facilitate the
      transition to dominant status, which ultimately leads to improved fitness for the
      previously reproductively-suppressed individual.

PMID- 22958306
TI  - Respiratory syncytial virus outbreak in neonatal intensive care unit: Impact of
      infection control measures plus palivizumab use.
AB  - BACKGROUND: The occurrence of a respiratory syncytial virus (RSV) outbreak in a
      Neonatal Intensive Care Unit (NICU) is related to unfavorable outcomes, as this
      infection can lead to respiratory distress and death in premature in infants.
      Report the successful control of an outbreak that occurred in April 2010 in a
      NICU. METHODS: After the index case, of 18 premature infants placed in the same
      room 10 infants were infected. Of those 10, 6 developed mild to moderate
      respiratory symptoms, 4 persisted asymptomatic and no death occurred. Contact and
      respiratory precautions were rapidly initiated, the infants were cohorted in 3
      different rooms and palivizumab was administered to all contacts. RESULTS: The
      outbreak was controlled and no new cases were subsequently indentified.
      CONCLUSION: Standard infection control measures plus palivizumab prophylaxis were
      efficient in rapid control of the outbreak.

PMID- 22958307
TI  - Evaluation of the efficacy of topically administered imidacloprid + pyriproxyfen
      and orally administered spinosad against cat fleas (Ctenocephalides felis):
      Impact of treated dogs on flea life stages in a simulated home environment.
AB  - BACKGROUND: Cat fleas, Ctenocephalides felis, are one of the most common
      ectoparasites infesting dogs and their environments. This study evaluated the
      efficacy of imidacloprid + pyriproxyfen (PPF) (Advantage(r) II for Dogs) and
      spinosad (Comfortis(r)) against established C. felis populations in dogs'
      simulated home environments. METHODS: Thirty Beagle dogs were randomly assigned
      to three groups of 10 dogs each and treated twice (Study Days 0 and 28) with
      imidacloprid + PPF, spinosad tablets, or a negative control (untreated). Dogs
      were housed individually in controlled simulated home environments capable of
      supporting the flea life cycle. Flea infestations were established in these
      environments by infesting each dog with 100 adult cat fleas on Study Days -21, 
      16 and 1. The impact of the treatments on fleas in the dogs' environments were
      assessed by collecting floor mat samples from each simulated home environment,
      incubating them for 32 days, and counting the number of emerging adult fleas. On
      Study Days 7, 14, 21, 28, 35, 42, 49 and 56, after collection of the cocoa
      matting samples, each dog was infested with an additional 5 +/- 1 fleas to
      maintain the environmental infestations. Flea comb counts on dogs were conducted
      on Study Days 0 (pretreatment) and 63. RESULTS: From Study Days 7-28, flea
      infestations in the imidacloprid + PPF environments were significantly lower (p <
      0.03) than those in the spinosad environments. Following the second treatment,
      flea infestations in all the imidacloprid + PPF environments fell to zero for the
      remainder of the study. In contrast, flea infestations persisted in some of the
      spinosad environments through the study's end.On Study Day 63 all 10 dogs treated
      with imidacloprid + PPF were flea free, while only one of the 10 spinosad treated
      dogs was flea free. Flea counts on the other 9 spinosad treated dogs ranged from
      3 to 46 fleas/dog (geometric mean = 8.6). A mean of 405 adult fleas/animal were
      recovered from the control dogs on Study Day 63. CONCLUSION: Flea infestations in
      environments of dogs treated with imidacloprid + PPF declined more rapidly than
      in those containing dogs treated with spinosad. Flea infestations were completely
      eliminated by Study Day 56 in environments of dogs treated with imidacloprid +
      PPF, but persisted through the study's end in some of environments of dogs
      treated with spinosad.

PMID- 22958308
TI  - Progress of genome wide association study in domestic animals.
AB  - Domestic animals are invaluable resources for study of the molecular architecture
      of complex traits. Although the mapping of quantitative trait loci (QTL)
      responsible for economically important traits in domestic animals has achieved
      remarkable results in recent decades, not all of the genetic variation in the
      complex traits has been captured because of the low density of markers used in
      QTL mapping studies. The genome wide association study (GWAS), which utilizes
      high-density single-nucleotide polymorphism (SNP), provides a new way to tackle
      this issue. Encouraging achievements in dissection of the genetic mechanisms of
      complex diseases in humans have resulted from the use of GWAS. At present, GWAS
      has been applied to the field of domestic animal breeding and genetics, and some
      advances have been made. Many genes or markers that affect economic traits of
      interest in domestic animals have been identified. In this review, advances in
      the use of GWAS in domestic animals are described.

PMID- 22958309
TI  - A national survey of health service infrastructure and policy impacts on access
      to computerised CBT in Scotland.
AB  - BACKGROUND: NICE recommends computerised cognitive behavioural therapy (cCBT) for
      the treatment of several mental health problems such as anxiety and depression.
      cCBT may be one way that services can reduce waiting lists and improve capacity
      and efficiency. However, there is some doubt about the extent to which the
      National Health Service (NHS) in the UK is embracing this new health technology
      in practice. This study aimed to investigate Scottish health service
      infrastructure and policies that promote or impede the implementation of cCBT in
      the NHS. METHODS: A telephone survey of lead IT staff at all health board areas
      across Scotland to systematically enquire about the ability of local IT
      infrastructure and IT policies to support delivery of cCBT. RESULTS: Overall,
      most of the health boards possess the required software to use cCBT programmes.
      However, the majority of NHS health boards reported that they lack dedicated
      computers for patient use, hence access to cCBT at NHS sites is limited.
      Additionally, local policy in the majority of boards prevent staff from routinely
      contacting patients via email, skype or instant messenger, making the delivery of
      short, efficient support sessions difficult. CONCLUSIONS: Conclusions: Overall
      most of the infrastructure is in place but is not utilised in ways that allow
      effective delivery. For cCBT to be successfully delivered within a guided support
      model, as recommended by national guidelines, dedicated patient computers should
      be provided to allow access to online interventions. Additionally, policy should
      allow staff to support patients in convenient ways such as via email or live
      chat. These measures would increase the likelihood of achieving Scottish health
      service targets to reduce waiting time for psychological therapies to 18 weeks.

PMID- 22958310
TI  - Main characteristics and participation rate of European adolescents included in
      the HELENA study.
AB  - BACKGROUND: Participation rate and response rate are key issues in a cross
      sectional large-scale epidemiological study. The objective of this paper is to
      describe the study population and to evaluate participation and response rate as
      well as the key nutritional status variables in male and female adolescents
      involved in the HELENA study. METHODS: A multi-stage random cluster sampling with
      a target sample of 3000 adolescents aged [12.5 to 17.5] years, stratified for
      geographical location and age, was carried out. Information for participants and
      non-participants (NP) was compared, and participation and response rates to
      specific questionnaires were discussed. RESULTS: 3,865 adolescents aged [12.5 to
      17.5] years (1,845 females) participated in the HELENA study, of whom 1,076 (568
      females) participated in the blood sampling. 3,528 (1,845 females) adolescents
      were finally kept for statistical analysis. Participation rates for the schools
      and classes differed importantly between countries. The participation rate of
      pupils within the participating classes also differed importantly between
      countries. Sex ratio, mean age and BMI were similar between NP and participating
      adolescents within each centre, and in the overall sample. For all the
      questionnaires included in the database, the response rate of questionnaires was
      high (more than 80% of questions were completed). CONCLUSION: From this study it
      could be concluded that participation rate differed importantly between
      countries, though no bias could be identified when comparing the key study
      variables between participants and non-participants. Response rate for
      questionnaires was very high. Future studies investigating lifestyle and health
      in adolescents can optimize their methods when considering the opportunities and
      barriers observed in the HELENA study.

PMID- 22958311
TI  - In search of markers of treatment failure and poor prognosis in IPAH - the value
      of mosaic lung attenuation pattern on thin-section CT scans.
AB  - Despite the development of specific therapies for pulmonary arterial
      hypertension (PAH) some patients fail to respond to such treatment. One of the
      potential reasons for the unresponsiveness to targeted therapies may be the
      presence of fibrous occlusion of small pulmonary veins that accompanies pre
      capillary arteriopathy. This type of pathologic change is called pulmonary veno
      occlusive disease (PVOD). Underdiagnosed PVOD occurs probably in 5-10% of
      idiopathic pulmonary hypertension (IPAH) and in a substantial proportion of PAH
      related to connective tissue diseases (mainly in scleroderma). A definite
      diagnosis of PVOD requires histological examination of lung sample, but surgical
      lung biopsy in pulmonary hypertension is combined with high risk of bleeding.
      Thus major interest is focused on a non-invasive diagnostic approach enabling
      early recognition of PVOD and referral for lung transplantation. The present
      review is focused on the radiological features suggestive of PVOD-like
      vasculopathy in PAH.

PMID- 22958312
TI  - Isolation and molecular characterization of vancomycin-resistant Enterococcus
      faecium from swine in Michigan, USA.
AB  - In 2008, we identified vancomycin-resistant enterococci (VRE) in Michigan swine,
      which was the first report of VRE in livestock from North America. Continued
      sampling in 2009 and 2010 was conducted to determine whether VRE persisted in
      Michigan. In 2009, swine faecal and feed samples (n=56), county fair pig barn
      manure samples (n=9) and pooled Michigan State Fair pig barn manure samples
      (n=18) were screened for VRE. In 2010, swine faecal samples were collected from
      26 county fairs (n=73) and nine commercial swine farms in six states (n=28).
      Recovered VRE isolates were molecularly evaluated by polymerase chain reaction,
      restriction fragment length polymorphism, pulsed-field gel electrophoresis
      (PFGE), S1 nuclease digestion and multilocus sequence typing (MLST). Six VRE
      isolates were identified in 2009 from the State Fair, and another six (8.2%) were
      recovered from the five county fairs in 2010. All 12 isolates were highly related
      to the first-reported VRE from Michigan swine: all were confirmed to be
      vancomycin-resistant Enterococcus faecium (VREf) carrying vanA gene on Tn1546
      (Type D), were negative for IS1251, hyl and esp gene, carried a 150-160 kb
      megaplasmid, and have closely similar PFGE patterns with >80% similarity.
      Classified as ST5, ST6 or ST185 by MLST, all belong to the clonal complex 5, a
      strain recognized to be circulating among European pigs. This study reveals that
      VREf are widespread in Michigan swine and persist in the historical absence of
      the use of agricultural glycopeptides.

PMID- 22958313
TI  - Prevention of sternal dehiscence with the sternum external fixation (Stern-E-Fix)
      corset--randomized trial in 750 patients.
AB  - BACKGROUND: The main objective of this study will be to determine the effects of
      a new advanced sternum external fixation (Stern-E-Fix) corset on prevention of
      sternal instability and mediastinitis in high-risk patients. METHODS: This
      prospective, randomized study (January 2009 - June 2011) comprised 750 male
      patients undergoing standard median sternotomy for cardiac procedures (78% CABG).
      Patients were divided in two randomized groups (A, n = 380: received a Stern-E
      Fix corset postoperatively for 6 weeks and B, n = 370: control group received a
      standard elastic thorax bandage). In both groups, risk factors for sternal
      dehiscence and preoperative preparations were similar. RESULTS: Wound infections
      occurred in n = 13 (3.42%) pts. in group A vs. n = 35 (9.46%) in group B. In
      group A, only 1 patient presented with sternal dehiscence vs. 22 pts. in group B.
      In all 22 patients, sternal rewiring followed by antibiotic therapy was needed.
      Mediastinitis related mortality was none in A versus two in B. Treatment failure
      in group B was more than five times higher than in A (p = 0.01); the mean length
      of stay in hospital was 12.5 +/- 7.4 days (A) versus 18 +/- 15.1 days (B)
      (p=0.002). Re-operation for sternal infection was 4 times higher in group B. Mean
      ventilation time was relatively longer in B (2.5 vs. 1.28 days) (p = 0.01). The
      mean follow-up period was 8 weeks (range 6 - 12 weeks). CONCLUSIONS: We
      demonstrated that using an external supportive sternal corset (Stern-E-Fix)
      yields a significantly better and effective prevention against development of
      sternal dehiscence and secondary sternal infection in high-risk poststernotomy
      patients.

PMID- 22958314
TI  - Dietary protein to maximize resistance training: a review and examination of
      protein spread and change theories.
AB  - An appreciable volume of human clinical data supports increased dietary protein
      for greater gains from resistance training, but not all findings are in
      agreement. We recently proposed "protein spread theory" and "protein change
      theory" in an effort to explain discrepancies in the response to increased
      dietary protein in weight management interventions. The present review aimed to
      extend "protein spread theory" and "protein change theory" to studies examining
      the effects of protein on resistance training induced muscle and strength gains.
      Protein spread theory proposed that there must have been a sufficient spread or %
      difference in g/kg/day protein intake between groups during a protein
      intervention to see muscle and strength differences. Protein change theory
      postulated that for the higher protein group, there must be a sufficient change
      from baseline g/kg/day protein intake to during study g/kg/day protein intake to
      see muscle and strength benefits. Seventeen studies met inclusion criteria. In
      studies where a higher protein intervention was deemed successful there was, on
      average, a 66.1% g/kg/day between group intake spread versus a 10.2% g/kg/day
      spread in studies where a higher protein diet was no more effective than control.
      The average change in habitual protein intake in studies showing higher protein
      to be more effective than control was +59.5% compared to +6.5% when additional
      protein was no more effective than control. The magnitudes of difference between
      the mean spreads and changes of the present review are similar to our previous
      review on these theories in a weight management context. Providing sufficient
      deviation from habitual intake appears to be an important factor in determining
      the success of additional protein in enhancing muscle and strength gains from
      resistance training. An increase in dietary protein favorably effects muscle and
      strength during resistance training.

PMID- 22958315
TI  - Chronic pain treatment and health service utilization of veterans with hepatitis
      C virus infection.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infection is estimated to affect 2% of the
      general U.S. population and chronic pain is a common comorbidity among persons
      with HCV. The primary purpose of this study was to compare health service
      utilization of U.S. military veterans with HCV with and without the presence of
      comorbid chronic pain. DESIGN: Cross-sectional study with retrospective review of
      patient medical records. PATIENTS:  One hundred seventy-one U.S. military
      veterans with confirmed HCV, recruited through a single U.S. Veterans
      Administration hospital. OUTCOME MEASURES: Medical service utilization data from
      the past 5 years were extracted from participants' electronic medical records.
      RESULTS: Sixty-four percent of veterans with HCV (N = 110) had chronic pain.
      Veterans with HCV and chronic pain utilized more health services including total
      inpatient stays (odds ratio [OR] = 2.58 [1.46, 4.56]) and days hospitalized for
      psychiatric services (OR = 5.50 [3.37, 8.99]), compared to participants with HCV
      and no chronic pain, after statistically adjusting for demographic, psychiatric,
      substance use, medical comorbidity, and disability covariates. In addition, those
      with HCV and chronic pain had more total outpatient visits with primary care
      providers (OR = 1.73 [1.15, 2.59]), physical therapists (OR = 9.57 [4.79,
      19.11]), and occupational therapists (OR = 2.72 [1.00, 7.48]). CONCLUSIONS: 
      Patients with HCV and chronic pain utilize medical services to a greater extent
      than patients with HCV but no chronic pain. Future studies that examine the
      efficacy of both pharmacological and nonpharmacological pain treatment for
      patients with comorbid HCV and chronic pain appear warranted.

PMID- 22958316
TI  - Adolescents with prenatal cocaine exposure show subtle alterations in striatal
      surface morphology and frontal cortical volumes.
AB  - BACKGROUND: Published structural neuroimaging studies of prenatal cocaine
      exposure (PCE) in humans have yielded somewhat inconsistent results, with several
      studies reporting no significant differences in brain structure between exposed
      subjects and controls. Here, we sought to clarify some of these discrepancies by
      applying methodologies that allow for the detection of subtle alterations in
      brain structure. METHODS: We applied surface-based anatomical modeling methods to
      magnetic resonance imaging (MRI) data to examine regional changes in the shape
      and volume of the caudate and putamen in adolescents with prenatal cocaine
      exposure (n = 40, including 28 exposed participants and 12 unexposed controls,
      age range 14 to 16 years). We also sought to determine whether changes in
      regional brain volumes in frontal and subcortical regions occurred in adolescents
      with PCE compared to control participants. RESULTS: The overall volumes of the
      caudate and putamen did not significantly differ between PCE participants and
      controls. However, we found significant (P <0.05, uncorrected) effects of levels
      of prenatal exposure to cocaine on regional patterns of striatal morphology.
      Higher levels of prenatal cocaine exposure were associated with expansion of
      certain striatal subregions and with contraction in others. Volumetric analyses
      revealed no significant changes in the volume of any subcortical region of
      interest, but there were subtle group differences in the volumes of some frontal
      cortical regions, in particular reduced volumes of caudal middle frontal cortices
      and left lateral orbitofrontal cortex in exposed participants compared to
      controls. CONCLUSIONS: Prenatal cocaine exposure may lead to subtle and
      regionally specific patterns of regional dysmorphology in the striatum and
      volumetric changes in the frontal lobes. The localized and bidirectional nature
      of effects may explain in part the contradictions in the existing literature.

PMID- 22958317
TI  - Moh's micrographic surgery for the management of a periocular mast cell tumor in
      a dog.
AB  - A 3-year-old neutered male boxer dog presented with a 6-month history of a waxing
      and waning mass of the left dorsotemporal eyelid margin. Cytology and biopsy
      confirmed a diagnosis of mast cell neoplasia. Systemic staging of the dog failed
      to reveal any evidence of metastatic neoplasia. Owing to the location of the
      tumor within the eyelid margin and the wide surgical margins recommended for
      excision of mast cell tumors, Mohs micrographic surgery (MMS) was chosen for its
      potential to conserve tissues while providing intraoperative confirmation the
      tumor was completely excised. Utilizing MMS horizontal sectioning technique, 100%
      of the surgical margins were assessed prior to closure of the surgical wound.
      This represents the first time a comprehensive MMS protocol was used in a
      veterinary patient under general anesthesia.

PMID- 22958318
TI  - Priority actions to fight antibiotic resistance: results of an international
      meeting.

PMID- 22958319
TI  - Relationship between disease severity and D-dimer levels measured with two
      different methods in pulmonary embolism patients.
AB  - Pulmonary embolism (PE) is diagnosed with increasing frequency nowadays due to
      advances in the diagnostic methods and the increased awareness of the disease.
      There is a tendency to use non invasive diagnostic methods for all diseases. D
      dimer is a fibrin degradation product. We aimed to detect the relationship
      between disease severity and the D-dimer levels measured with two different
      methods. We compared D-dimer levels in cases of massive vs. non-massive PE. A
      total of 89 patients who were diagnosed between 2006 and 2008 were included in
      the study. Group 1 included patients whose D-dimer levels were measured with the
      immunoturbidimetric polyclonal antibody method (D-dimerPLUS(r)), while Group 2
      patients made use of the immunoturbidimetric monoclonal antibody method
      (InnovanceD-DIMER(r)). In each group, the D-dimer levels of those with massive
      and non-massive PE were compared, using the Mann Whitney U test. The mean age of
      Group 1 (25 F/26 M) was 56.0 +/- 17.9 years, and that of Group 2 (22 F/16 M) was
      52.9 +/- 17.9 years. There was no statistical difference in gender and mean age
      between the two groups (p > 0.05). In Group 1, the mean D-dimer level of massive
      cases (n = 7) was 1444.9 +/- 657.9 MUg/L and that of nonmassive PE (n = 34) was
      1304.7 +/- 350.5 MUg/L (p > 0.05). In Group 2, the mean D-dimer level of massive
      cases (n = 6) was 9.7 +/- 2.2 mg/L and that of non-massive PE (n = 32) was 5.9 +/
      1.3 mg/L (p < 0.05). The mean D-dimer levels of massive cases as measured with
      the immunoturbidimetric monoclonal antibody method were significantly higher.
      Pulmonary embolism patients whose D-dimer levels are higher (especially higher
      than 6.6 mg/L) should be considered as possibly having massive embolism.
      Diagnostic procedures and management can be planned according to this finding.

PMID- 22958320
TI  - Individual units rather than entire hospital as the basis for improvement: the
      example of two Methicillin resistant Staphylococcus aureus cohort studies.
AB  - BACKGROUND: Two MRSA surveillance components exist within the German national
      nosocomial infection surveillance system KISS: one for the whole hospital (i.e.
      only hospital based data and no rates for individual units) and one for ICU-based
      data (rates for each individual ICU). The objective of this study was to analyze
      which surveillance system (a hospital based or a unit based) leads to a greater
      decrease in incidence density of nosocomial MRSA METHODS: Two cohort studies of
      surveillance data were used: Data from a total of 224 hospitals and 359 ICUs in
      the period from 2004 to 2009. Development over time was described first for both
      surveillance systems. In a second step only data were analyzed from those
      hospitals/ICUs with continuous participation for at least four years. Incidence
      rate ratios (IRR) with 95% confidence intervals were calculated to compare
      incidence densities between different time intervals. RESULTS: In the baseline
      year the mean MRSA incidence density of hospital acquired MRSA cases was 0.25 and
      the mean incidence density of ICU-acquired MRSA was 1.25 per 1000 patient days.
      No decrease in hospital-acquired MRSA rates was found in a total of 111 hospitals
      with continuous participation in the hospital- based system. However, in 159 ICUs
      with continuous participation in the unit-based system, a significant decrease of
      29% in ICU-acquired MRSA was identified. CONCLUSIONS: A unit-based approach of
      surveillance and feedback seems to be more successful in decreasing nosocomial
      MRSA rates, compared to a hospital-based approach. Therefore each surveillance
      system should provide unit-based data to stimulate activities on the unit level.

PMID- 22958321
TI  - Absence of dry season Plasmodium parasitaemia, but high rates of reported acute
      respiratory infection and diarrhoea in preschool-aged children in Kaedi, southern
      Mauritania.
AB  - BACKGROUND: The epidemiology of malaria in the Senegal River Gorgol valley,
      southern Mauritania, requires particular attention in the face of ongoing and
      predicted environmental and climate changes. While "malaria cases" are reported
      in health facilities throughout the year, past and current climatic and
      ecological conditions do not favour transmission in the dry season (lack of
      rainfall and very high temperatures). Moreover, entomological investigations in
      neighbouring regions point to an absence of malaria transmission in mosquito
      vectors in the dry season. Because the clinical signs of malaria are non-specific
      and overlap with those of other diseases (e.g. acute respiratory infections and
      diarrhoea), new research is needed to better understand malaria transmission
      patterns in this region to improve adaptive, preventive and curative measures.
      METHODS: We conducted a multipurpose cross-sectional survey in the city of Kaedi
      in April 2011 (dry season), assessing three major disease patterns, including
      malaria. Plasmodium spp. parasite rates were tested among children aged 6-59
      months who were recruited from a random selection of households using a rapid
      diagnostic test and microscopic examination of Giemsa-stained thick and thin
      blood films. Acute respiratory infection and diarrhoea were the two other
      diseases investigated, administering a parental questionnaire to determine the
      reported prevalence among participating children. FINDINGS: No Plasmodium
      infection was found in any of the 371 surveyed preschool-aged children using two
      different diagnostic methods. Acute respiratory infections and diarrhoea were
      reported in 43.4% and 35.0% of the participants, respectively. About two thirds
      of the children with acute respiratory infections and diarrhoea required medical
      follow-up by a health worker. CONCLUSIONS: Malaria was absent in the present dry
      season survey in the capital of the Gorgol valley of Mauritania, while acute
      respiratory infections and diarrhea were highly prevalent. Surveys should be
      repeated towards the end of rainy season, which will enhance our understanding of
      the potential changes in malaria transmission in a region known as 'hot spot' of
      predicted climate change.

PMID- 22958322
TI  - Rituximab treatment in a case of antisynthetase syndrome with severe interstitial
      lung disease and acute respiratory failure.
AB  - We present a case of severe interstitial pneumonitis, mild polyarthritis and
      polymyositis, and Raynaud's syndrome with the presence of anti-Jo-1 antibodies,
      which had been diagnosed as anti-synthetase syndrome. The presence, however, of
      anti-Ro/SSA antibodies led us to understand that we were dealing here with a more
      severe form of interstitial lung disease. The patient was treated for acute
      respiratory failure but he showed resistance to glucocorticoids and cyclosporine.
      Thus, he was treated with infusions of anti-CD20 therapy (rituximab): his
      clinical conditions improved very rapidly and a significant decrease in the
      activity of pulmonary disease was detected using high-resolution computerized
      tomography (HRCT) of the thorax and pulmonary function tests.

PMID- 22958323
TI  - Routine dipstick urinalysis in daily practice of Belgian occupational physicians.
AB  - BACKGROUND: Little work has been done to assess the quality of health care and
      the use of evidence-based methods by occupational physicians in Belgium.
      Therefore, the main objective is to describe one aspect of occupational health
      assessments, namely the common use of dipstick urinalysis, and to compare the
      current practice with international guidelines. METHODS: A self-administered
      questionnaire was mailed to 211 members of the Scientific Association of
      Occupational Medicine in the Dutch speaking part of Belgium. RESULTS: A total of
      120 occupational physicians responded, giving a response rate of 57%. Dipstick
      urinalysis was a routine investigation for the vast majority of physicians (69%).
      All test strips screened for protein and in 90% also for blood. Occupational
      health services offered clinical tests to satisfy customer wants as international
      guidelines do not recommend screening for haematuria and proteinuria in
      asymptomatic adults. A lack of knowledge concerning positive testing and referral
      criteria was demonstrated in almost half of the study participants. CONCLUSIONS:
      Belgian occupational physicians still routinely perform dipstick testing although
      there is no evidence to support this screening in healthy workers. To practice
      evidence-based medicine, occupational physicians need more instruction and
      training. Development and implementation of more guidelines is not only of use
      for the individual practitioner, it may also enhance professionalization and
      efficiency of occupational health care.

PMID- 22958324
TI  - Rationale for the turin conference/congress 2012.

PMID- 22958325
TI  - Biology and fertility life table of the green aphid Chaetosiphon fragaefolli on
      strawberry cultivars.
AB  - Our objective was to study the biology and develop a fertility life table for the
      aphid Chaetosiphon fragaefolli (Cockerell) (Hemiptera: Aphididae) on leaves of
      strawberry, Fragaria * ananassa, Duchesne ex Rozier (Rosales: Rosaceae), of the
      cultivars Albion, Aromas, Camarosa, Camino Real, Diamante, Earlibrite, and
      Saborosa. This study was conducted under controlled conditions: 25 +/- 1 (
      degrees )C, 70 +/- 10% RH, and 12:12 L:D . Arenas were set up consisting of
      leaves inside Petri dishes containing 3% agar. Female aphids obtained after the
      last nymphal ecdysis were individually placed in arenas for 24 hours. The
      following biological parameters were evaluated: duration and survival of the
      nymph stage and of the life cycle (nymph-nymph), daily and total fecundity, and
      adult longevity. The aphids completed their biological cycle on all of the
      cultivars. The shortest durations (in days) of the nymphal stage were on the
      cultivars Camino Real and Camarosa (8.67 and 8.74 days, respectively), and the
      longest was on Aromas (11.12 days). The lowest survival was on cultivar Aromas
      (51%) and the highest on Saborosa (96%). When the time to development to the
      adult stage was compared, the aphids developed fastest (14.63 days) and survival
      was highest (96%) on cultivar Saborosa. Aphids reared on cultivar Aromas leaves
      had the longest pre-reproductive period (8.74 days), the greatest longevity
      (26.88 days), and the longest duration of the life cycle (19.76 days). Based on
      the fertility life table, cultivars Camarosa and Saborosa were the most favorable
      for development of C. fragaefolli, while Albion and Aromas were the most
      inadequate for aphid development.

PMID- 22958326
TI  - Adjusting team involvement: a grounded theory study of challenges in utilizing a
      surgical safety checklist as experienced by nurses in the operating room.
AB  - BACKGROUND: Even though the use of perioperative checklists have resulted in
      significant reduction in postoperative mortality and morbidity, as well as
      improvements of important information communication, the utilization of
      checklists seems to vary, and perceived barriers are likely to influence
      compliance. In this grounded theory study we aimed to explore the challenges and
      strategies of performing the WHO's Safe Surgical Checklist as experienced by the
      nurses appointed as checklist coordinators. METHODS: Grounded theory was used in
      gathering and analyzing data from observations of the checklist used in the
      operating room, in conjunction with single and focus group interviews. A
      purposeful sample of 14 nurse-anesthetists and operating room nurses as surgical
      team members in a tertiary teaching hospital participated in the study. RESULTS:
      The nurses' main concern regarding checklist utilization was identified as "how
      to obtain professional and social acceptance within the team". The emergent
      grounded theory of "adjusting team involvement" consisted of three strategies;
      distancing, moderating and engaging team involvement. The use of these strategies
      explains how they resolved their challenges. Each strategy had corresponding
      conditions and consequences, determining checklist compliance, and how the
      checklist was used. CONCLUSION: Even though nurses seem to have a loyal attitude
      towards the WHO's checklist regarding their task work, they adjusted their
      surgical team involvement according to practical, social and professional
      conditions in their work environment. This might have resulted in the incomplete
      use of the checklist and therefore a low compliance rate. Findings also
      emphasized the importance of: a) management support when implementing WHO's Safe
      Surgical Checklist, and b) interprofessional education approach to local
      adaptation of the checklists use.

PMID- 22958327
TI  - Extrapulmonary features of bronchiectasis: muscle function, exercise capacity,
      fatigue, and health status.
AB  - BACKGROUND: There are limited number of studies investigating extrapulmonary
      manifestations of bronchiectasis. The purpose of this study was to compare
      peripheral muscle function, exercise capacity, fatigue, and health status between
      patients with bronchiectasis and healthy subjects in order to provide documented
      differences in these characteristics for individuals with and without
      bronchiectasis. METHODS: Twenty patients with bronchiectasis (43.5 +/- 14.1
      years) and 20 healthy subjects (43.0 +/- 10.9 years) participated in the study.
      Pulmonary function, respiratory muscle strength (maximal expiratory pressure -
      MIP - and maximal expiratory pressure - MEP), and dyspnea perception using the
      Modified Medical Research Council Dyspnea Scale (MMRC) were determined. A six
      minute walk test (6MWT) was performed. Quadriceps muscle, shoulder abductor, and
      hand grip strength (QMS, SAS, and HGS, respectively) using a hand held
      dynamometer and peripheral muscle endurance by a squat test were measured.
      Fatigue perception and health status were determined using the Fatigue Severity
      Scale (FSS) and the Leicester Cough Questionnaire (LCQ), respectively. RESULTS:
      Number of squats, 6MWT distance, and LCQ scores as well as lung function testing
      values and respiratory muscle strength were significantly lower and MMRC and FSS
      scores were significantly higher in patients with bronchiectasis than those of
      healthy subjects (p < 0.05). In bronchiectasis patients, QMS was significantly
      associated with HGS, MIP and MEP (p < 0.05). The 6MWT distance was significantly
      correlated to LCQ psychological score (p < 0.05). The FSS score was significantly
      associated with LCQ physical and total and MMRC scores (p < 0.05). The LCQ
      psychological score was significantly associated with MEP and 6MWT distance (p <
      0.05). CONCLUSIONS: Peripheral muscle endurance, exercise capacity, fatigue and
      health status were adversely affected by the presence of bronchiectasis. Fatigue
      was associated with dyspnea and health status. Respiratory muscle strength was
      related to peripheral muscle strength and health status, but not to fatigue,
      peripheral muscle endurance or exercise capacity. These findings may provide
      insight for outcome measures for pulmonary rehabilitation programs for patients
      with bronchiectasis.

PMID- 22958328
TI  - An empirical investigation into beliefs about collaborative practice among
      maternity care providers.
AB  - OBJECTIVE: To investigate agreement with the National Health and Medical Research
      Council (NHMRC) definition of collaboration in maternity care by care providers,
      and to examine their preferences for models of care in order to shed light on the
      lack of success in implementing collaborative practice. METHODS: Maternity care
      providers completed a survey in Queensland. The final sample consisted of 337
      participants, including 281 midwives (83.38%), 35 obstetricians (10.39%), and 21
      general practitioners (6.23%). RESULTS: Ninety-one percent of the participants
      agreed with the NHMRC definition of collaboration: Midwives (M=5.97, s.d.=1.2)
      and doctors (obstetricians and general practitioners: M=5.7, s.d.=1.35) did not
      differ significantly in their level of agreement with definition (t (332)=-1.8,
      P=.068). However, 72% of doctors endorsed a doctor-led model of care, whereas
      only 6.8% of midwives indicated agreement with it. Fewer (56%) doctors agreed
      with the midwife-led model of care, whereas 99.3% of midwives endorsed it.
      CONCLUSION: The concept of collaboration does not recognise the different
      interpretations by midwives and doctors of its impact on their roles and
      behaviours. Successful collaborative practice requires the development of
      guidelines that recognise these differences and specify the communication
      behaviour that would assist midwives and doctors to practice collaboratively.

PMID- 22958329
TI  - Suboptimal management of central nervous system infections in children: a multi
      centre retrospective study.
AB  - OBJECTIVE: We aimed to audit the regional management of central nervous system
      (CNS) infection in children. METHODS: The study was undertaken in five district
      general hospitals and one tertiary paediatric hospital in the Mersey region of
      the UK. Children admitted to hospital with a suspected CNS infection over a three
      month period were identified. Children were aged between 4 weeks and 16 years
      old. Details were recorded from the case notes and electronic records. We
      measured the appropriateness of management pathways as outlined by national and
      local guidelines. RESULTS: Sixty-five children were identified with a median age
      of 6 months (range 1 month to 15 years). Ten had a CNS infection: 4 aseptic
      meningitis, 3 purulent meningitis, 3 encephalitis [2 with herpes simplex virus
      (HSV) type 1]. A lumbar puncture (LP) was attempted in 50 (77%) cases but only 43
      had cerebrospinal fluid (CSF) available for analysis. Of these 24 (57%) had a
      complete standard set of tests performed. Fifty eight (89%) received a third
      generation cephalosporin. Seventeen (26%) also received aciclovir with no obvious
      indication in 9 (53%). Only 11 (65%) of those receiving aciclovir had CSF herpes
      virus PCR. Seventeen had cranial imaging and it was the first management step in
      14. Treatment lengths of both antibiotics and aciclovir were highly variable: one
      child with HSV encephalitis was only treated with aciclovir for 7 days.
      CONCLUSIONS: The clinical management of children with suspected CNS infections
      across the Mersey region is heterogeneous and often sub-optimal, particularly for
      the investigation and treatment of viral encephalitis. National guidelines for
      the management of viral encephalitis are needed.

PMID- 22958331
TI  - A draft of the genome and four transcriptomes of a medicinal and pesticidal
      angiosperm Azadirachta indica.
AB  - BACKGROUND: The Azadirachta indica (neem) tree is a source of a wide number of
      natural products, including the potent biopesticide azadirachtin. In spite of its
      widespread applications in agriculture and medicine, the molecular aspects of the
      biosynthesis of neem terpenoids remain largely unexplored. The current report
      describes the draft genome and four transcriptomes of A. indica and attempts to
      contextualise the sequence information in terms of its molecular phylogeny,
      transcript expression and terpenoid biosynthesis pathways. A. indica is the first
      member of the family Meliaceae to be sequenced using next generation sequencing
      approach. RESULTS: The genome and transcriptomes of A. indica were sequenced
      using multiple sequencing platforms and libraries. The A. indica genome is AT
      rich, bears few repetitive DNA elements and comprises about 20,000 genes. The
      molecular phylogenetic analyses grouped A. indica together with Citrus sinensis
      from the Rutaceae family validating its conventional taxonomic classification.
      Comparative transcript expression analysis showed either exclusive or enhanced
      expression of known genes involved in neem terpenoid biosynthesis pathways
      compared to other sequenced angiosperms. Genome and transcriptome analyses in A.
      indica led to the identification of repeat elements, nucleotide composition and
      expression profiles of genes in various organs. CONCLUSIONS: This study on A.
      indica genome and transcriptomes will provide a model for characterization of
      metabolic pathways involved in synthesis of bioactive compounds, comparative
      evolutionary studies among various Meliaceae family members and help annotate
      their genomes. A better understanding of molecular pathways involved in the
      azadirachtin synthesis in A. indica will pave ways for bulk production of
      environment friendly biopesticides.

PMID- 22958330
TI  - Reference percentiles for FEV(1) and BMI in European children and adults with
      cystic fibrosis.
AB  - BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using
      the percent predicted FEV(1) and BMI Z-score referenced against a healthy
      population, since achieving normality is the ultimate goal of CF care.
      Referencing against age and sex matched CF peers may provide valuable information
      for patients and for comparison between CF centers or populations. Here, we used
      a large database of European CF patients to compute CF specific reference
      equations for FEV(1) and BMI, derived CF-specific percentile charts and compared
      these European data to their nearest international equivalents. METHODS: 34859
      FEV(1) and 40947 BMI observations were used to compute European CF specific
      percentiles. Quantile regression was applied to raw measurements as a function of
      sex, age and height. Results were compared with the North American equivalent for
      FEV(1) and with the WHO 2007 normative values for BMI. RESULTS: FEV(1) and BMI
      percentiles illustrated the large variability between CF patients receiving the
      best current care. The European CF specific percentiles for FEV(1) were
      significantly different from those in the USA from an earlier era, with higher
      lung function in Europe. The CF specific percentiles for BMI declined relative to
      the WHO standard in older children. Lung function and BMI were similar in the two
      largest contributing European Countries (France and Germany). CONCLUSION: The CF
      specific percentile approach applied to FEV(1) and BMI allows referencing
      patients with respect to their peers. These data allow peer to peer and
      population comparisons in CF patients.

PMID- 22958332
TI  - Increased responses to the actions of fibroblast growth factor 21 on energy
      balance and body weight in a seasonal model of adiposity.
AB  - The present study aimed to investigate the actions of fibroblast growth factor 21
      (FGF21) on energy balance in a natural model of relative fatness, the Siberian
      hamster. Hamsters were studied under long days (LD) to promote weight gain, or
      short days to induce weight loss, and treated with rhFGF21 (3 mg/kg/day) via s.c.
      minipumps for 14 days. On days 7-9, detailed assessments of ingestive behaviour,
      metabolic gas exchange and locomotor activity were made. FGF21 caused substantial
      (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the
      end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared
      to vehicle controls, which is comparable to the natural body weight loss observed
      in SD. Epididymal fat pads, a correlate of total carcass fat content, were
      reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found
      in SD. Body weight loss in LD was associated with a reduction in food intake (P <
      0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating
      increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal
      increase in oxygen consumption and carbon dioxide production into the early light
      phase in hamsters in LD, indicating increased energy expenditure, although
      locomotor activity was unaffected. These data suggest a greater efficacy of FGF21
      in hamsters in LD compared to those in SD, which is consistent with both the
      peripheral and possibly central actions of FGF21 with respect to promoting a lean
      phenotype. The observed differences in FGF21 sensitivity may relate to day length
      induced changes in adipose tissue mass.

PMID- 22958333
TI  - Body mass index and depressive symptoms: instrumental-variables regression with
      genetic risk score.
AB  - The causal role of obesity in the development of depression remains uncertain. We
      applied instrumental-variables regression (Mendelian randomization) to examine
      the association of adolescent and adult body mass index (BMI) with adult
      depressive symptoms. Participants were from the Young Finns prospective cohort
      study (n = 1731 persons, 2844 person-observations), with repeated measurements of
      BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk
      score of 31 single nucleotide polymorphisms previously identified as robust
      genetic markers of body weight was used as a proxy for variation in BMI. In
      standard linear regression analysis, higher adult depressive symptoms were
      predicted by higher adolescent BMI (B = 0.33, CI = 0.06-0.60, P = 0.017) and
      adult BMI (B = 0.47, CI = 0.32-0.63, P < 0.001). These associations were
      replicated in instrumental-variables analysis with genetic risk score as
      instrument (B = 1.96, CI = 0.03-3.90, P = 0.047 for adolescent BMI; B = 1.08, CI
      = 0.11-2.04, P = 0.030 for adult BMI). The association for adolescent BMI was
      significantly stronger in the instrumented analysis compared to standard
      regression (P = 0.04). These findings provide additional evidence to support a
      causal role for high BMI in increasing symptoms of depression. However, the
      present analysis also demonstrates potential limitations of applying Mendelian
      randomization when using complex phenotypes. 

PMID- 22958335
TI  - Preparation of bismuth nanowire encased in quartz template for Hall measurements
      using focused ion beam processing.
AB  - Forming electrodes on opposite sides of an individual bismuth nanowire was
      attempted to prepare for Hall measurements. Although a 1-mm-long bismuth nanowire
      which is completely covered with a quartz template has been successfully
      fabricated to prevent oxidation, it is very difficult to attach Hall electrodes
      on the opposite sides of the nanowire due to the quartz covering. One side of the
      cylindrical quartz template was removed by polishing without exposure of the
      nanowire to the atmosphere; the thickness between the polished template surface
      and the nanowire was estimated to be several micrometers. Focused ion beam
      processing was successfully employed to expose both surfaces of the nanowire
      under high vacuum by removing part of the quartz template. A carbon thin film was
      then deposited in situ on the wire surface to fabricate an electrical contact on
      the bismuth nanowire sample. Furthermore, the energy dispersive X-ray analysis
      was performed to the area processed by focused ion beam, and the bismuth
      component of the nanowire was successfully detected. It was confirmed that the
      focused ion beam processing was applicable to attach electrodes to bismuth
      nanowire for Hall measurement.

PMID- 22958334
TI  - Respiratory involvement in inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's
      disease (CD) and are due to a dysregulation of the antimicrobial defense normally
      provided by the intestinal mucosa. This inflammatory process may extend outside
      the bowel to many organs and also to the respiratory tract. The respiratory
      involvement in IBD may be completely asymptomatic and detected only at lung
      function assessment, or it may present as bronchial disease or lung parenchymal
      alterations. Corticosteroids, both systemic and aerosolized, are the mainstay of
      the therapeutical approach, while antibiotics must be also administered in the
      case of infectious and suppurative processes, whose sequels sometimes require
      surgical intervention. The relatively high incidence of bronchopulmonary
      complications in IBD suggests the need for a careful investigation of these
      patients in order to detect a possible respiratory involvement, even when they
      are asymptomatic.

PMID- 22958336
TI  - Twenty years of antimicrobial resistance control programme in a regional multi
      hospital institution, with focus on emerging bacteria (VRE and CPE).
AB  - BACKGROUND: Assistance Publique-Hopitaux de Paris (APHP), the largest public
      health care institution in France (38 hospitals, 23,000 beds, serving 11.6
      millions inhabitants) launched in 1993 a long term programme to control and
      survey multidrug resistant bacteria (MDR). FINDINGS: AP-HP MDR programme
      consisted in successive waves of actions: bundle measures to survey and control
      cross transmission of MRSA and extended-spectrum betalactamase producing
      enterobacteria (ESBL) in 1993, large campaign to promote the use of alcohol-based
      hand rub solution (ABHRS) in 2001, specific strategy to quickly control the
      spread of emerging MDR (vancomycin resistant Enterococcus, VRE; carbapenemase
      producing enterobacteria, CPE) in 2006, large campaign to decrease antibiotics
      consumption in 2006.Following this programme, the ABHRS consumption dramatically
      increased, the antibiotic consumption decreased by 10%, the incidence of MRSA,
      including MRSA bacteraemia, decreased by 2/3, all VRE and CPE events were rapidly
      controlled. However, the incidence of ESBL, mainly Klebsiella pneumoniae and
      Escherichia coli, that remained low and stable until 2003 increased markedly
      afterwards, justifying adapting our programme in the future. CONCLUSION: A
      sustained and coordinated strategy can lead to control multidrug resistant
      bacteria at the level of a large multihospital institution.

PMID- 22958337
TI  - Modified Kuhnt-Szymanowski surgical procedure for secondary cicatricial ectropion
      in a horse.
AB  - A 1-year-old Dutch Warmblood gelding was presented to the University of Florida's
      Large Animal Hospital (UF-LAH) for correction of ectropion of the right lower
      eyelid. The ectropion was the result of a lower eyelid laceration. A primary
      repair was performed by the referring veterinarian; however, the horse
      prematurely removed the sutures and the wound healed with inversion of the eyelid
      margin. Surgical correction of the entropion, with removal of tissue from the
      lower eyelid, resulted in cicatricial ectropion. During the initial evaluation at
      UF-LAH, a corneal ulcer was noted in the right eye because of exposure from the
      anatomically nonfunctional lower eyelid. A modified Kuhnt-Szymanowski procedure
      was performed to correct the ectropion and repair the eyelid margin. The surgical
      site healed appropriately with an acceptable cosmetic and functional result. No
      recurrences of corneal ulcers in the right eye were reported in the 18 months
      following surgical correction of the ectropion.

PMID- 22958338
TI  - NADPH oxidase mediates the oxygen-glucose deprivation/reperfusion-induced
      increase in the tyrosine phosphorylation of the N-methyl-D-aspartate receptor
      NR2A subunit in retinoic acid differentiated SH-SY5Y Cells.
AB  - BACKGROUND: Evidence exists that oxidative stress promotes the tyrosine
      phosphorylation of N-methyl-D-aspartate receptor (NMDAR) subunits during post
      ischemic reperfusion of brain tissue. Increased tyrosine phosphorylation of NMDAR
      NR2A subunits has been reported to potentiate receptor function and exacerbate
      NMDAR-induced excitotoxicity. Though the effect of ischemia on tyrosine
      phosphorylation of NMDAR subunits has been well documented, the oxidative stress
      signaling cascades mediating the enhanced tyrosine phosphorylation of NR2A
      subunits remain unclear. RESULTS: We report that the reactive oxygen species
      (ROS) generator NADPH oxidase mediates an oxidative stress-signaling cascade
      involved in the increased tyrosine phosphorylation of the NR2A subunit in post
      ischemic differentiated SH-SY5Y neuroblastoma cells. Inhibition of NADPH oxidase
      attenuated the increased tyrosine phosphorylation of the NMDAR NR2A subunit,
      while inhibition of ROS production from mitochondrial or xanthine oxidase sources
      failed to dampen the post-ischemic increase in tyrosine phosphorylation of the
      NR2A subunit. Additionally, inhibition of NADPH oxidase blunted the interaction
      of activated Src Family Kinases (SFKs) with PSD-95 induced by
      ischemia/reperfusion. Lastly, inhibition of NADPH oxidase also markedly reduced
      cell death in post-ischemic SH-SY5Y cells stimulated by NMDA. CONCLUSIONS: These
      data indicate that NADPH oxidase has a key role in facilitating NMDAR NR2A
      tyrosine phosphorylation via SFK activation during post-ischemic reperfusion.

PMID- 22958339
TI  - Serotypes of Salmonella isolated from faeces of patients with acute diarrhoea in
      Gwangju Area, Korea, during 2000-2009.
AB  - The purpose of this study was to determine the changing pattern of Salmonella
      serotypes causing acute diarrhoea in humans in Gwangju area, Korea, during 2000
      2009. A total of 596 Salmonella isolated from culture of 29,896 faecal samples of
      patients with acute diarrhoea were included in this study. Faecal samples were
      collected from local hospitals and clinics in Gwangju area during January 2000
      December 2009. The mean annual frequency of isolates for the 10 years was 2.0%
      (range, 0.9-6.0). The isolates were serologically classified into 43 different
      serotypes. The 10 most common serotypes were Salmonella Enteritidis (47.9%), S.
      Typhimurium (20.4%), S. Braenderup (3.2%), S. Montevideo (2.9%), S. Paratyphi B
      (2.9%), S. London (2.3%), S. Bardo (1.7%), S. Virchow (1.7%), S. Infantis (1.5%)
      and S. Typhi (1.5%), accounting for 86% of all the isolates. Temporal variations
      were observed in the distribution of different Salmonella serotypes over the
      years, and only S. Enteritidis and S. Typhimurium were persistent throughout the
      study period. Although age specificity varied with serotypes, Salmonella was
      isolated most frequently from children below 5 years of age (179/596, 30.0%). A
      seasonal trend was apparent, and the highest rates were found in the summer
      months. This is the first report of the annual frequency of isolation of
      Salmonella serotypes, and seasonal and age-specific patterns of salmonellosis in
      humans in Gwangju area, Korea, over a decade-long period.

PMID- 22958340
TI  - Pulmonary function tests and rehabilitation in 2012: beyond sitting position.

PMID- 22958341
TI  - Dietary patterns on weekdays and weekend days in 4-14-year-old Danish children.
AB  - Little is known about dietary patterns on weekdays and weekend days in children,
      and the aim of the present study was to investigate 4-14-year-old children's
      dietary patterns specifically on weekdays (Monday-Thursday) and weekend days
      (Saturday-Sunday). Dietary data were derived from the Danish National Survey of
      Dietary Habits and Physical Activity 2003-8, where a total of 784 children aged 4
      14 years completed a 7 d pre-coded food record. Principal component analysis was
      used to identify dietary patterns in the age groups 4-6, 7-10 and 11-14 years.
      Consistently, two dietary patterns, labelled 'processed' and 'health conscious',
      emerged on both weekdays and weekend days. Factor scores from corresponding
      dietary patterns were significantly correlated between weekdays and weekend days
      with the exception of the 'health conscious' pattern in the 7-10-year-olds.
      Within each age group, children with high agreement for the 'processed' pattern
      had a significantly higher dietary energy density, which was reflected in
      significantly higher intakes of sugar-sweetened beverages and lower intakes of
      fruit and vegetables, compared with children with high agreement for the 'health
      conscious' pattern (P< 0.05). Moreover, these variables indicated less healthy
      dietary intakes on weekend days than on weekdays for both patterns. In
      conclusion, two distinct dietary patterns, labelled 'processed' and 'health
      conscious', were identified on both weekdays and weekend days for each age group.
      While overall major dietary patterns may somewhat track between weekdays and
      weekends, the specific foods actually eaten became less healthy during weekends.

PMID- 22958342
TI  - Deficits in postural control in individuals with COPD - emerging evidence for an
      important secondary impairment.
AB  - Emerging evidence suggests that individuals with COPD demonstrate reductions in
      balance control that may be associated with an increased fall risk. The purpose
      of this review is to: 1) provide a brief overview of balance control and its
      assessment; 2) review relevant literature describing balance impairment in
      individuals with COPD; and 3) highlight important areas for future research. The
      observation of balance deficits and an increased fall risk in patients with COPD
      suggests the need for including balance assessment and training for patients
      enrolled in pulmonary rehabilitation who may be vulnerable. Further studies are
      needed to determine which aspects of balance are affected and to examine the
      impact of interventions.

PMID- 22958343
TI  - Immigrants' use of emergency primary health care in Norway: a registry-based
      observational study.
AB  - BACKGROUND: Emigrants are often a selected sample and in good health, but
      migration can have deleterious effects on health. Many immigrant groups report
      poor health and increased use of health services, and it is often claimed that
      they tend to use emergency primary health care (EPHC) services for non-urgent
      purposes. The aim of the present study was to analyse immigrants' use of EPHC,
      and to analyse variations according to country of origin, reason for immigration,
      and length of stay in Norway. METHODS: We conducted a registry based study of all
      immigrants to Norway, and a subsample of immigrants from Poland, Germany, Iraq
      and Somalia, and compared them with native Norwegians. The material comprised all
      electronic compensation claims for EPHC in Norway during 2008. We calculated
      total contact rates, contact rates for selected diagnostic groups and for
      services given during consultations. Adjustments for a series of socio
      demographic and socio-economic variables were done by multiple logistic
      regression analyses. RESULTS: Immigrants as a whole had a lower contact rate than
      native Norwegians (23.7% versus 27.4%). Total contact rates for Polish and German
      immigrants (mostly work immigrants) were 11.9% and 7.0%, but for Somalis and
      Iraqis (mostly asylum seekers) 31.8% and 33.6%. Half of all contacts for Somalis
      and Iraqis were for non-specific pain, and they had relatively more of their
      contacts during night than other groups. Immigrants' rates of psychiatric
      diagnoses were low, but increased with length of stay in Norway. Work immigrants
      suffered less from respiratory and gastrointestinal infections, but had more
      injuries and higher need for sickness certification. All immigrant groups, except
      Germans, were more often given a sickness certificate than native Norwegians. Use
      of interpreter was reduced with increasing length of stay. All immigrant groups
      had an increased need for long consultations, while laboratory tests were most
      often used for Somalis and Iraqis. CONCLUSIONS: Immigrants use EPHC services less
      than native Norwegians, but there are large variations among immigrant groups.
      Work immigrants from Germany and Poland use EPHC considerably less, while asylum
      seekers from Somalia and Iraq use these services more than native Norwegians.

PMID- 22958344
TI  - Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges.
AB  - Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome characterized by
      pulmonary surfactant accumulation within the alveolar spaces. It occurs with a
      reported prevalence of 0.1 per 100,000 individuals and in distinct clinical
      forms: autoimmune (previously referred to as the idiopathic form, represents the
      vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony
      Stimulating Factor (GM-CSF) auto-antibodies; GMAbs), secondary (is a consequence
      of underlying disorders), congenital (caused by mutations in the genes encoding
      for the GM-CSF receptor), and PAP-like syndromes (disorders associated with
      surfactant gene mutations). The clinical course of PAP is variable, ranging from
      spontaneous remission to respiratory failure. Whole lung lavage (WLL) is the
      current standard treatment for PAP patients and although it is effective in the
      majority of cases, disease persistence is not an unusual outcome, even if disease
      is well controlled by WLL.In this paper we review the therapeutic strategies
      which have been proposed for the treatment of PAP patients and the progress which
      has been made in the understanding of the disease pathogenesis.

PMID- 22958345
TI  - Effects of "Bioactive" amino acids leucine, glutamate, arginine and tryptophan on
      feed intake and mRNA expression of relative neuropeptides in broiler chicks.
AB  - Feed intake control is vital to ensuring optimal nutrition and achieving full
      potential for growth and development in poultry. The aim of the present study was
      to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine
      on feed intake and the mRNA expression levels of hypothalamic Neuropeptide
      involved in feed intake regulation in broiler chicks. Leucine, glutamate,
      tryptophan or arginine was intra-cerebroventricularly (ICV) administrated to 4d
      old broiler chicks respectively and the feed intake were recorded at various time
      points. Quantitative PCR was performed to determine the hypothalamic mRNA
      expression levels of Neuropeptide Y (NPY), agouti related protein (AgRP), pro
      opiomelanocortin (POMC), melanocortin receptor 4 (MC4R) and corticotrophin
      releasing factor (CRF). Our results showed that ICV administration of L-leucine
      (0.15 or 1.5  MUmol) significantly (P < 0.05) increased feed intake up to 2 h
      post-administration period and elevated both hypothalamic NPY and AgRP mRNA
      expression levels. In contrast, ICV administration of L-glutamate (1.6  MUmol)
      significantly (P < 0.05) decreased feed intake 0.25, 0.5 and 2 h post-injection,
      and increased hypothalamic CRF and MC4R mRNA expression levels. Meanwhile, both L
      tryptophan (10 or 100  MUg) and L-arginine (20 or 200  MUg) had no significant
      effect on feed intake. These findings suggested that L-leucine and L-glutamate
      could act within the hypothalamus to influence food intake, and that both
      orexigenic and anorexigenic Neuropeptide genes might contribute directly to these
      effects.

PMID- 22958346
TI  - Ten-year decrease of acquired methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia at a single institution: the result of a multifaceted program
      combining cross-transmission prevention and antimicrobial stewardship.
AB  - BACKGROUND: In France, the proportion of MRSA has been over 25% since 2000.
      Prevention of hospital-acquired (HA) MRSA spread is based on isolation
      precautions and antibiotic stewardship. At our institution, before 2000, the
      Infection Disease and the Infection Control teams had failed to reduce HA-MRSA
      rates. OBJECTIVES AND METHODS: We implemented a multifaceted hospital-wide
      prevention program and measured the effects on HA-MRSA colonization and
      bacteremia rates between 2000 and 2009. From 2000 to 2003, active screening and
      decontamination of ICU patients, hospital wide alcohol based hand rubs (ABHR)
      use, control of specific classes of antibiotics, compliance audits, and feed
      backs to the care providers were successively implemented. The efficacy of the
      program was assessed by HA-MRSA colonized and bacteremic patient rates per 1000
      patient-days in patients hospitalized for more than twenty-four hours. RESULTS:
      Compliance with the isolation practices increased between 2000 and 2009.
      Consumption of ABHR increased from 6.8 L to 27.5 L per 1000 patient-days. The use
      of antibiotic Defined Daily Doses (DDD) per 1000 patient-days decreased by 31%.
      HA-MRSA colonization decreased by 84% from 1.09 to 0.17 per 1000 patient-days and
      HA-MRSA bacteremia by 93%, from 0.15 to 0.01 per 1000 patient-days (p < 10-7 for
      each rate). CONCLUSIONS: In an area highly endemic for MRSA, a multifaceted
      prevention program allows for sustainable reduction in HA-MRSA bacteremia rates.

PMID- 22958347
TI  - Diversity of planthoppers associated with the winter rice agroecosystems in
      southern Yunnan, China.
AB  - A field survey of the overwintering planthoppers (Hemiptera: Delphacidae)
      associated with the rice agroecosystems in southern Yunnan was carried out during
      January-February in 2010 and 2011. 22 species of planthoppers were collected and
      identified, with one species representing the subfamily Stenocraninae and the
      other 21 species in Delphacinae. Nycheuma cognatum (Muir), Peregrinus maidis
      (Ashmead), and Pseudosogata vatrenus (Fennah) were new provincial records for
      Yunnan. The pest species, Sogatella furcifera (Horvath), Nilaparvata lugens
      (Stal), and Laodelphax striatellus (Fallen) were able to overwinter in part of
      the survey range. 13 species were listed to be of economic importance. Abandoned
      rice paddies with dense Poaceae grasses (Poaceae) were the most favorable
      overwintering habitat. The survey range was divided into four regions and five
      areas based on natural geographical characteristics. The study demonstrated that
      winter temperature differentiation, terrains, and habitat differences were three
      factors affecting planthopper diversity. Planthopper species diversity showed a
      reductive trend from south to north and reflected a gradient of more severe
      winter temperatures. In addition, planthopper diversity was influenced by smaller
      scale differences in terrain and habitat, as evidenced by greater diversity in
      the valleys and low-altitude areas as compared to mid-mountain and Karst plain
      areas.

PMID- 22958349
TI  - Persistence of systemic inflammation in COPD in spite of smoking cessation.

PMID- 22958348
TI  - Complete genome sequence of Saccharothrix espanaensis DSM 44229(T) and comparison
      to the other completely sequenced Pseudonocardiaceae.
AB  - BACKGROUND: The genus Saccharothrix is a representative of the family
      Pseudonocardiaceae, known to include producer strains of a wide variety of potent
      antibiotics. Saccharothrix espanaensis produces both saccharomicins A and B of
      the promising new class of heptadecaglycoside antibiotics, active against both
      bacteria and yeast. RESULTS: To better assess its capabilities, the complete
      genome sequence of S. espanaensis was established. With a size of 9,360,653 bp,
      coding for 8,501 genes, it stands alongside other Pseudonocardiaceae with large
      genomes. Besides a predicted core genome of 810 genes shared in the family, S.
      espanaensis has a large number of accessory genes: 2,967 singletons when compared
      to the family, of which 1,292 have no clear orthologs in the RefSeq database. The
      genome analysis revealed the presence of 26 biosynthetic gene clusters
      potentially encoding secondary metabolites. Among them, the cluster coding for
      the saccharomicins could be identified. CONCLUSION: S. espanaensis is the first
      completely sequenced species of the genus Saccharothrix. The genome discloses the
      cluster responsible for the biosynthesis of the saccharomicins, the largest
      oligosaccharide antibiotic currently identified. Moreover, the genome revealed 25
      additional putative secondary metabolite gene clusters further suggesting the
      strain's potential for natural product synthesis.

PMID- 22958350
TI  - Hand hygiene: a way out of the deadlock.
AB  - Hospital-acquired infection costs money and lives. Improving compliance with hand
      hygiene is proving an intractable problem as initial gains often lack
      sustainability. A growing field of research suggests that health service managers
      may have a critical role in dealing with this issue, which crosses all
      professional boundaries.

PMID- 22958351
TI  - Fragile X syndrome: a pilot proton magnetic resonance spectroscopy study in
      premutation carriers.
AB  - PURPOSE: There is increasing evidence that neurodevelopmental differences in
      people with Fragile X syndrome (FraX) may be explained by differences in
      glutamatergic metabolism. Premutation carriers of FraX were originally considered
      to be unaffected although several recent reports demonstrate neuroanatomical,
      cognitive, and emotional differences from controls. However there are few studies
      on brain metabolism in premutation carriers of FraX. METHODS: We used proton
      magnetic resonance spectroscopy to compare neuronal integrity of a number of
      brain metabolites including N-Acetyl Aspartate, Creatine + Phosphocreatinine,
      Choline, myoInositol, and Glutamate containing substances (Glx) in 17 male
      premutation carriers of FraX and 16 male healthy control individuals. RESULTS:
      There was no significant between-group difference in the concentration of any
      measured brain metabolites. However there was a differential increase in N-acetyl
      aspartate with aging in premutation FraX individuals compared to controls.
      CONCLUSIONS: This is the first 1 H-MRS study to examine premutation FraX
      individuals. Although we demonstrated no difference in the concentration of any
      of the metabolites examined between the groups, this may be due to the large age
      ranges included in the two samples. The differential increase in NAA levels with
      aging may reflect an abnormal synaptic pruning process.

PMID- 22958352
TI  - Epidemiology of East Coast fever (Theileria parva infection) in Kenya: past,
      present and the future.
AB  - In this article, we review the epidemiology of East Coast fever (ECF), a tick
      borne infection of cattle, in Kenya. The major factors associated with
      epidemiology of ECF include the agro-ecological zone (AEZ), livestock production
      system (LPS) and both animal breed and age. These factors appear to influence the
      epidemiology of ECF through structured gradients. We further show that the
      gradients are dynamically shaped by socio-demographic and environmental
      processes. For a vector-borne disease whose transmission depends on environmental
      characteristics that influence vector dynamics, a change in the environment
      implies a change in the epidemiology of the disease. The review recommends that
      future ECF epidemiological studies should account for these factors and the
      dynamic interactions between them. In Kenya, ECF control has previously relied
      predominantly on tick control using acaricides and chemotherapy while ECF
      immunization is steadily being disseminated. We highlight the contribution of ECF
      epidemiology and economics in the design of production system and/or geographical
      area-specific integrated control strategies based on both the dynamic
      epidemiological risk of the disease and economic impacts of control strategies.
      In all production systems (except marginal areas), economic analyses demonstrate
      that integrated control in which ECF immunization is always an important
      component, can play an important role in the overall control of the disease.
      Indeed, Kenya has recently approved ECF immunization in all production systems
      (except in marginal areas). If the infrastructure of the vaccine production and
      distribution can be heightened, large ECF endemic areas are expected to be
      endemically stable and the disease controlled. Finally, the review points the way
      for future research by identifying scenario analyses as a critical methodology on
      which to base future investigations on how both dynamic livestock management
      systems and patterns of land use influence the dynamics and complexity of ECF
      epidemiology and the implications for control.

PMID- 22958353
TI  - Establishment and reinforcement of the national reference centers for human
      microbiology in Belgium.
AB  - BACKGROUND: Microbiology reference laboratories are critical in the development
      of high-quality clinical and public health services. In Belgium, the reference
      laboratories performed their activities on a voluntary basis and lacked a legal
      status. METHODS: Pathogens or groups of pathogens necessitating a national
      reference center (NRC) were prioritized based on diagnostic and epidemiologic
      relevance. Terms of reference for each of these pathogens were developed.
      RESULTS: Recently, 40 NRCs for different pathogens or groups of pathogens have
      been installed in Belgium to fulfill the following core functions: offering
      reference diagnostics, collecting reference materials, sharing information and
      scientific advice, participating in national and international networks,
      collaborating with research workgroups, and contributing to surveillance
      activities. CONCLUSIONS: These NRCs are important focal points of the national
      and international network in public health microbiology.

PMID- 22958354
TI  - Ask: a health advocacy program for adolescents with an intellectual disability: a
      cluster randomised controlled trial.
AB  - BACKGROUND: Adolescents with intellectual disability often have poor health and
      healthcare. This is partly as a consequence of poor communication and recall
      difficulties, and the possible loss of specialised paediatric services.
      METHODS/DESIGN: A cluster randomised trial was conducted with adolescents with
      intellectual disability to investigate a health intervention package to enhance
      interactions among adolescents with intellectual disability, their
      parents/carers, and general practitioners (GPs). The trial took place in
      Queensland, Australia, between February 2007 and September 2010. The intervention
      package was designed to improve communication with health professionals and
      families' organisation of health information, and to increase clinical activities
      beneficial to improved health outcomes. It consisted of the Comprehensive Health
      Assessment Program (CHAP), a one-off health check, and the Ask Health Diary,
      designed for on-going use. Participants were drawn from Special Education Schools
      and Special Education Units. The education component of the intervention was
      delivered as part of the school curriculum. Educators were surveyed at baseline
      and followed-up four months later. Carers were surveyed at baseline and after 26
      months. Evidence of health promotion, disease prevention and case-finding
      activities were extracted from GPs clinical records. Qualitative interviews of
      educators occurred after completion of the educational component of the
      intervention and with adolescents and carers after the CHAP. DISCUSSION:
      Adolescents with intellectual disability have difficulty obtaining many health
      services and often find it difficult to become empowered to improve and protect
      their health. The health intervention package proposed may aid them by augmenting
      communication, improving documentation of health encounters, and improving access
      to, and quality of, GP care. Recruitment strategies to consider for future
      studies in this population include ensuring potential participants can identify
      themselves with the individuals used in promotional study material, making direct
      contact with their families at the start of the study, and closely monitoring the
      implementation of the educational intervention. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov Identifier: NCT00519311.

PMID- 22958355
TI  - From Acta Botanica Sinica to JIPB: connecting Chinese plant science with the
      international community for 60 years.

PMID- 22958356
TI  - Role of quantitative CT in predicting postoperative FEV1 and chronic dyspnea in
      patients undergoing lung resection.
AB  - Lung resection is the mainstay of treatment in patients with early stage non
      small cell lung cancer. However, lung cancer patients often suffer from
      comorbidities and the respiratory reserve should be carefully evaluated
      preoperatively in order to avoid postoperative complications. Forced expiratory
      volume in 1 second (FEV1) is considered to be an index that depicts the patient's
      respiratory efficacy and its prediction has a key role in the preoperative
      evaluation of lung cancer patients with impaired lung function. Prediction of
      postoperative FEV1 is currently possible with the use of perfusion radionuclide
      lung scanning.Quantitative CT is the analysis of data acquired during normal
      chest CT scan using the system's software. By applying a dual threshold of -500
      to -910 Hounsfield Units, functional lung volumes are estimated and postoperative
      FEV1 can be predicted by reducing the preoperative measurement by the fraction of
      the part to be resected.Studies have shown that preoperative predictions
      correlate well with the actual postoperative measurements. Additionally,
      quantitative CT results are in good agreement with perfusion scintigraphy
      predictions. Newer radiological techniques such as perfusion MRI and co
      registered SPECT/CT have also been used in the preoperative evaluation with
      similar results.In conclusion, chest CT which is obligatory for staging, can be
      used for quantitative analysis of the already available data. It is technically
      simple, providing an accurate prediction of postoperative FEV1. Thus,
      quantitative CT appears to be a useful tool in the preoperative evaluation of
      lung cancer patients undergoing lung resection.

PMID- 22958357
TI  - Spatio-temporal scan statistics for the detection of outbreaks involving common
      molecular subtypes: using human cases of Escherichia coli O157:H7 provincial PFGE
      pattern 8 (National Designation ECXAI.0001) in Alberta as an example.
AB  - Molecular typing methods have become a common part of the surveillance of
      foodborne pathogens. In particular, pulsed-field gel electrophoresis (PFGE) has
      been used successfully to identify outbreaks of Escherichia coli O157:H7 in
      humans from a variety of food and environmental sources. However, some PFGE
      patterns appear commonly in surveillance systems, making it more difficult to
      distinguish between outbreak and sporadic cases based on molecular data alone. In
      addition, it is unknown whether these common patterns might have unique
      epidemiological characteristics reflected in their spatial and temporal
      distributions. Using E. coli O157:H7 surveillance data from Alberta, collected
      from 2000 to 2002, we investigated whether E. coli O157:H7 with provincial PFGE
      pattern 8 (national designation ECXAI.0001) clustered in space, time and space
      time relative to other PFGE patterns using the spatial scan statistic. Based on
      our purely spatial and temporal scans using a Bernoulli model, there did not
      appear to be strong evidence that isolates of E. coli O157:H7 with provincial
      PFGE pattern 8 are distributed differently from other PFGE patterns. However, we
      did identify space-time clusters of isolates with PFGE pattern 8, using a
      Bernoulli model and a space-time permutation model, which included known
      outbreaks and potentially unrecognized outbreaks or additional outbreak cases.
      There were differences between the two models in the space-time clusters
      identified, which suggests that the use of both models could increase the
      sensitivity of a quantitative surveillance system for identifying outbreaks
      involving isolates sharing a common PFGE pattern. 

PMID- 22958358
TI  - Unique and differential protein signatures within the mononuclear cells of HIV-1
      and HCV mono-infected and co-infected patients.
AB  - BACKGROUND: Pathogenesis of liver damage in patients with HIV and HCV co
      infection is complex and multifactorial. Although global awareness regarding HIV
      1/HCV co-infection is increasing little is known about the pathophysiology that
      mediates the rapid progression to hepatic disease in the co-infected individuals.
      RESULTS: In this study, we investigated the proteome profiles of peripheral blood
      mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1/HCV co-infected
      patients. The results of high-resolution 2D gel electrophoresis and PD quest
      software quantitative analysis revealed that several proteins were differentially
      expressed in HIV-1, HCV, and HIV-1/HCV co-infection. Liquid chromatography-mass
      spectrometry and Mascot database matching (LC-MS/MS analysis) successfully
      identified 29 unique and differentially expressed proteins. These included
      cytoskeletal proteins (tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1),
      chaperones and co-chaperones (HSP90-beta and stress-induced phosphoprotein),
      metabolic and pre-apoptotic proteins (guanosine triphosphate [GTP]-binding
      nuclear protein Ran, the detoxifying enzyme glutathione S-transferase (GST) and
      Rho GDP-dissociation inhibitor (Rho-GDI), proteins involved in cell prosurvival
      mechanism, and those involved in matrix synthesis (collagen binding protein 2
      [CBP2]). The six most significant and relevant proteins were further validated in
      a group of mono- and co-infected patients (n = 20) at the transcriptional levels.
      CONCLUSIONS: The specific pro- and anti- apoptotic protein signatures revealed in
      this study could facilitate the understanding of apoptotic and protective immune
      mediated mechanisms underlying HIV-1 and HCV co-infection and their implications
      on liver disease progression in co-infected patients.

PMID- 22958360
TI  - A new start: Journal of Animal Science and Biotechnology re-launches with BioMed
      Central.

PMID- 22958359
TI  - The sarcoid granuloma: 'epithelioid' or 'lymphocytic-epithelioid' granuloma?
AB  - BACKGROUND: This study aims to analyze the structure and quantities of cellular
      elements in sarcoid granulomas. METHODS: We investigated 34 transbronchial lung
      biopsy samples obtained from 34 sarcoid patients. The quantity and composition of
      the cellular elements inside a granuloma were determined by the quantitative
      stereometry method, employing the numerical density as a stereological method.
      RESULTS: A total of 102 sarcoid granulomas were analyzed. The central part of all
      granulomas was occupied by epithelioid cells. Besides these, giant cells,
      lymphocytes, macrophages and plasma cells were also seen. The mean numerical
      density of all the cells in the central part of a sarcoid granuloma was 111,751
      mm-3. Lymphocytes prevailed in number, exceeding the total count of all other
      cells. With a mean numerical density of 74,321 mm-3, lymphocytes were twice as
      numerous as both epithelioid cells and macrophages with a mean numerical density
      of 37,193 mm-3. CONCLUSIONS: Lymphocytes are the predominant cell type in the
      central part of a sarcoid granuloma, significantly exceeding both epithelioid
      cells and macrophages in number, raising the question if the term "epithelioid
      granuloma", routinely used to designate sarcoid granulomas, is correct, or if it
      would be more logical to call them "lymphocytic-epithelioid granulomas" instead.
      TRIAL REGISTRATION: This study was supported by the Serbian Ministry of Science
      and Environmental Protection Grant Number 175006/2011.

PMID- 22958361
TI  - Metaherpetic corneal disease in a dog associated with partial limbal stem cell
      deficiency and neurotrophic keratitis.
AB  - OBJECTIVE: To describe clinical, in vivo confocal microscopic, histopathologic,
      and immunohistochemical features of a dog with metaherpetic corneal disease that
      developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1)
      dendritic ulcerative keratitis. CASE DESCRIPTION: A 7-year-old, spayed-female,
      Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative
      keratitis. Following resolution of ulcerative keratitis, sectoral peripheral
      superficial corneal gray opacification, vascularization, and pigmentation slowly
      migrated centripetally to the axial cornea of both eyes. Corneal sensitivity
      measured with a Cochet-Bonnet esthesiometer was dramatically and persistently
      reduced. In vivo corneal confocal microscopic examination revealed regions of
      epithelium with a conjunctival phenotype. In these areas, the surface epithelium
      was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet
      cells and Langerhans cells were frequent, and the subbasal nerve plexus was
      completely absent or markedly diminished. Histopathologic abnormalities in the
      globes were restricted to the superficial cornea and included sectoral corneal
      conjunctivalization, increased anterior stromal spindle cells, and
      vascularization. Immunohistochemical evaluation of the corneas with anti
      neurotublin antibody demonstrated attenuation of the epithelial and subbasal
      nerve plexuses with marked stromal hyperinnervation and increased numbers of
      morphologically abnormal neurites. CONCLUSIONS: Similar to herpes simplex virus
      keratitis in humans, CHV-1 ulcerative keratitis may be associated with the
      development of chronic degenerative corneal disease in dogs. In the described
      dog, this chronic corneal disease included progressive corneal opacification
      because of partial limbal stem cell deficiency and neurotrophic keratitis. Long
      term monitoring of dogs following resolution of active CHV-1 keratitis may be
      indicated, particularly when ulcerations persist for an extended period.

PMID- 22958362
TI  - System size reduction in stochastic simulations of the facilitated diffusion
      mechanism.
AB  - BACKGROUND: Site-specific Transcription Factors (TFs) are proteins that bind to
      specific sites on the DNA and control the activity of a target gene by enhancing
      or decreasing the rate at which the gene is transcribed by RNA polymerase. The
      process by which TF molecules locate their target sites is a key component of
      transcriptional regulation. Therefore it is essential to gain insight into the
      mechanisms by which TFs search for the target sites.Research in this area uses
      experimental and analytical approaches, but also stochastic simulations of the
      search process. Previous work based on stochastic simulations focussed only on
      short sequences, primarily for reasons of technical feasibility. Many of these
      studies had to disregard possible biases introduced by reducing a genome-wide
      system to a smaller subsystem. In particular, we identified crucial parameters
      that require adjustment, which were not adequately changed in these previous
      studies. RESULTS: We investigated several methods that adequately adapt the
      parameters of stochastic simulations of the facilitated diffusion, when the full
      sequence space is reduced to smaller regions of interest. We found two methods
      that scale the system accordingly: the copy number model and the association rate
      model. We systematically compared the results produced by simulations of the
      subsystem with respect to the original system. Our results confirmed that the
      copy number model is adequate only for high abundance TFs, while for low
      abundance TFs the association rate model is the only one that reproduces with
      high accuracy the results of the full system. CONCLUSIONS: We propose a strategy
      to reduce the size of the system that adequately adapts important parameters to
      capture the behaviour of the full system. This enables correct simulations of a
      smaller sequence space (which can be as small as 100 Kbp) and, thus, provides
      independence from computationally intensive genome-wide simulations of the
      facilitated diffusion mechanism.

PMID- 22958363
TI  - Effects of the dual PPAR-alpha/gamma agonist aleglitazar on glycaemic control and
      organ protection in the Zucker diabetic fatty rat.
AB  - AIMS: To evaluate the effects of aleglitazar, a dual peroxisome proliferator
      activated receptor-alpha/gamma agonist, on the development of diabetes-related
      organ dysfunction, in relation to glycaemic and lipid changes, in Zucker diabetic
      fatty (ZDF) rats. METHODS: Six-week-old, male ZDF rats received aleglitazar 0.3
      mg/kg/day or vehicle as food admix for 13 weeks (n = 10 per group). Age-matched
      male Zucker lean rats served as non-diabetic controls. Plasma and renal markers
      were measured at several time points. Histopathology and quantitative
      immunohistochemistry were performed at 13 weeks. RESULTS: Glycated haemoglobin
      (5.4 vs. 9.2%) and blood glucose (8.3 +/- 0.3 vs. 26.1 +/- 1.0 mmol/l) were
      significantly reduced at 12 weeks with aleglitazar versus vehicle-treated ZDF
      rats (both p < 0.01), while aleglitazar preserved near-normal plasma insulin
      levels. Aleglitazar prevented the development of hypertriglyceridaemia (1.4 +/-
      0.1 vs. 8.5 +/- 0.9 mmol/l) and reduced plasma non-esterified fatty acids (0.09
      +/- 0.02 vs. 0.26 +/- 0.04 mmol/l) relative to vehicle-treated animals (both p <
      0.01). Urinary glucose and protein concentrations were significantly reduced at
      13 weeks with aleglitazar versus vehicle-treated rats (both p < 0.01). Consistent
      with its effect on glycaemic control, aleglitazar protected beta-cell morphology,
      as evidenced by preservation of islet integrity, and reduction of beta-cell
      apoptosis and islet fibrosis. Aleglitazar prevented renal glomerular hypertrophy,
      podocyte degeneration, glomerulosclerosis, tubulo-interstitial lesions and
      development of cataracts. CONCLUSIONS: Aleglitazar strongly improved glycaemic
      and lipid parameters while protecting key tissues, including the pancreas,
      kidneys and eyes, against diabetes-associated structural and functional changes
      in the ZDF rat.

PMID- 22958364
TI  - Cryptogenic organizing pneumonia after radiotherapy for breast cancer.
AB  - We report a case of fever, dyspnea, respiratory failure and migratory, recurrent
      and bilateral lung opacities 4 months after radiotherapy and hormone therapy
      following surgery for breast cancer. Computerized tomography (CT) scans showed
      infiltrates outside the radiation fields. Bronchoalveolar lavage revealed
      lymphocytic alveolitis, whereas laboratory analysis demonstrated a mild systemic
      inflammation. Systemic steroids resulted in clinical and radiological
      improvement, but a disease relapse was evident at withdrawal of therapy, with
      definitive clinical and radiological normalization after a second cycle of
      therapy. This is a case of cryptogenic organizing pneumonia (COP) (previously
      known as bronchiolitis obliterans organizing pneumonia) primed by radiotherapy,
      as in previously reported cases. It is extremely important to be aware of the
      possibility of this complication, in order to optimize radiation and hormone
      treatment of breast cancer.

PMID- 22958366
TI  - MicroRNA-130b and microRNA-374b mediate the effect of maternal dietary protein on
      offspring lipid metabolism in Meishan pigs.
AB  - To investigate whether the effect of maternal dietary protein on offspring lipid
      metabolism is mediated by microRNA (miRNA), fourteen Meishan sows were fed either
      low-protein (LP, half of standard protein (SP) level, n 7) or SP (n 7) diets
      throughout gestation and lactation periods. PPAR-gamma and CCAAT/enhancer-binding
      protein-beta (C/EBP-beta) protein expression was evaluated. The expression of
      miRNA predicted to directly target PPAR-gamma and C/EBP-beta in the subcutaneous
      fat of offspring at weaning age was determined, and the functions of these
      potential miRNA were verified. The results showed that piglet body weight and
      back fat thickness were significantly decreased in the LP group compared with the
      SP group (P<0.05). The protein level of PPAR-gamma was significantly decreased
      and C/EBP-beta protein expression was also decreased, though not significantly
      (P=0.056), in the subcutaneous fat of the LP group. Furthermore, miRNA expression
      analysis showed that miR-130b, targeting the PPAR-gamma 3'-untranslated region
      (UTR), and miR-374b, targeting the C/EBP-beta 3'-UTR, were significantly
      increased in the LP group compared with the SP group; other candidate regulatory
      miRNA were expressed similarly in both groups. Dual luciferase activity assay
      results indicated that miR-130b directly recognised and bound to the 3'-UTR of
      PPAR-gamma and thereby suppressed PPAR-gamma gene expression. Similar results
      were found for miR-374b and the 3'-UTR of C/EBP-beta. The present study showed
      that miR-130b and miR-374b are involved in the effect of maternal dietary protein
      on offspring lipid metabolism in pigs. These results shed new light on our
      understanding of the maternal effect on offspring lipid deposition.

PMID- 22958365
TI  - Effort-reward imbalance and quality of life of healthcare workers in military
      hospitals: a cross-sectional study.
AB  - BACKGROUND: Taiwan's National Defense Bureau has been merging its hospitals and
      adjusting hospital accreditation levels since the beginning of 2006. These
      changes have introduced many stressors to the healthcare workers in these
      hospitals. This study investigates the association between job stress,
      psychological morbidity and quality of life in healthcare workers in three
      military hospitals. METHODS: We posted surveys to 1269 healthcare workers in
      three military hospitals located in southern Taiwan. The surveys included the
      General Health Questionnaire (GHQ), the World Health Organization Quality of Life
      Questionnaire (WHOQOL-BREF), and the Effort-Reward Imbalance (ERI) Questionnaire.
      High effort-reward (ER) ratio and overcommitment were defined when scores fell
      into the upper tertile of the total distribution. RESULTS: The survey was
      completed by 791 healthcare workers. On average, women reported a higher ERI than
      men. High ERI was associated with younger age, higher psychological morbidity,
      and poor physical and psychological QOL domains in this population. High ER ratio
      and high overcommitment were associated with psychological morbidity and poor QOL
      in both sexes. However, high ER ratio was not significantly associated with the
      social QOL domain in either sexes or the physical QOL domain in males.
      CONCLUSIONS: There was a clear association between ERI and QOL in the healthcare
      workers in the military hospitals under reorganization and accreditation in this
      study. We found ER ratio and overcommitment to be suitable indicators of job
      stress.

PMID- 22958367
TI  - Anatomy and neuro-pathophysiology of the cough reflex arc.
AB  - Coughing is an important defensive reflex that occurs through the stimulation of
      a complex reflex arc. It accounts for a significant number of consultations both
      at the level of general practitioner and of respiratory specialists. In this
      review we first analyze the cough reflex under normal conditions; then we analyze
      the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of
      this review is to provide the anatomic and pathophysiologic elements of
      evaluation of the complex and multiple etiologies of cough.

PMID- 22958368
TI  - Synthesis and anti-HIV properties of new carbamate prodrugs of AZT.
AB  - A series of new 5'-O-carbamate prodrugs of AZT have been prepared. The stability
      in biological media, anti-HIV properties and pharmacokinetic parameters in dogs
      were evaluated. The compounds display moderate anti-HIV activity in cell culture.
      After oral administration of carbamate IV in dogs, both intact prodrug IV and
      released AZT were discovered in dog blood. Pharmacokinetic parameters of the
      compound IV were estimated. Half-life (T(1/2)) of AZT released after oral
      administration of IV in dogs was close to that after administration of AZT
      itself, and time to the maximum concentration (T(max)) of AZT released from IV
      was two and three times longer compared with that of AZT and H-phosphonate AZT,
      respectively. Acute toxicity was more than five times less if compared with AZT.
      As a result, we consider this series of carbamate derivatives of AZT as
      perspective for development of anti-HIV agents.

PMID- 22958369
TI  - Multi-predator effects produced by functionally distinct species vary with prey
      density.
AB  - Determining when multiple predator species provide better pest suppression than
      single species is a key step towards developing ecologically-informed biological
      control strategies. Theory and experiments predict that resource partitioning
      among functionally different predator species can strengthen prey suppression,
      because as a group they can access more prey types than functionally redundant
      predators. However, this prediction assumes that competition limits predation by
      functionally similar predators. Differences in prey density can alter the
      strength of competition, suggesting that prey abundance may modulate the effect
      of combining functionally diverse species. The experiment documented here
      examined the potential for functional differences among predator species to
      promote suppression of an insect pest, the Colorado potato beetle, Leptinotarsa
      decemlineata (Say) (Coleoptera: Chrysomelidae), at different prey densities.
      Predation was compared at two prey densities between microcosms that contained
      one predator species or two functionally distinct species: the lady beetle,
      Coleomegilla maculata De Geer (Coleoptera: Coccinellidae) that kills early L.
      decemlineata instars, and the soldier bug, Podisus maculiventris Say (Hemiptera:
      Pentatomidae) that kills late instars. The data show that combining these
      predators increased predation only when prey densities were low. This suggests
      that multiple predator species may only provide greater biological control than
      single species in systems where prey is limiting.

PMID- 22958370
TI  - Quantitative comparisons of select cultured and uncultured microbial populations
      in the rumen of cattle fed different diets.
AB  - BACKGROUND: The number and diversity of uncultured ruminal bacterial and
      archaeal species revealed by 16S rRNA gene (rrs) sequences greatly exceeds that
      of cultured bacteria and archaea. However, the significance of uncultured
      microbes remains undetermined. The objective of this study was to assess the
      numeric importance of select uncultured bacteria and cultured bacteria and the
      impact of diets and microenvironments within cow rumen in a comparative manner.
      RESULTS: Liquid and adherent fractions were obtained from the rumen of Jersey
      cattle fed hay alone and Holstein cattle fed hay plus grain. The populations of
      cultured and uncultured bacteria present in each fraction were quantified using
      specific real-time PCR assays. The population of total bacteria was similar
      between fractions or diets, while total archaea was numerically higher in the hay
      fed Jersey cattle than in the hay-grain-fed Holstein cattle. The population of
      the genus Prevotella was about one log smaller than that of total bacteria. The
      populations of Fibrobacter succinogenes, Ruminococcus flavefaciens, the genus
      Butyrivibrio, and R. albus was at least one log smaller than that of genus
      Prevotella. Four of the six uncultured bacteria quantified were as abundant as F.
      succinogenes, R. flavefaciens and the genus Butyrivibrio. In addition, the
      populations of several uncultured bacteria were significantly higher in the
      adherent fractions than in the liquid fractions. These uncultured bacteria may be
      associated with fiber degradation. CONCLUSIONS: Some uncultured bacteria are as
      abundant as those of major cultured bacteria in the rumen. Uncultured bacteria
      may have important contribution to ruminal fermentation. Population dynamic
      studies of uncultured bacteria in a comparative manner can help reveal their
      ecological features and importance to rumen functions.

PMID- 22958371
TI  - The effectiveness of knowledge translation strategies used in public health: a
      systematic review.
AB  - BACKGROUND: Literature related to the effectiveness of knowledge translation (KT)
      strategies used in public health is lacking. The capacity to seek, analyze, and
      synthesize evidence-based information in public health is linked to greater
      success in making policy choices that have the best potential to yield positive
      outcomes for populations. The purpose of this systematic review is to identify
      the effectiveness of KT strategies used to promote evidence-informed decision
      making (EIDM) among public health decision makers. METHODS: A search strategy was
      developed to identify primary studies published between 2000-2010. Studies were
      obtained from multiple electronic databases (CINAHL, Medline, EMBASE, and the
      Cochrane Database of Systematic Reviews). Searches were supplemented by hand
      searching and checking the reference lists of included articles. Two independent
      review authors screened studies for relevance, assessed methodological quality of
      relevant studies, and extracted data from studies using standardized tools.
      RESULTS: After removal of duplicates, the search identified 64, 391 titles
      related to KT strategies. Following title and abstract review, 346 publications
      were deemed potentially relevant, of which 5 met all relevance criteria on full
      text screen. The included publications were of moderate quality and consisted of
      five primary studies (four randomized controlled trials and one interrupted time
      series analysis). Results were synthesized narratively. Simple or single KT
      strategies were shown in some circumstances to be as effective as complex,
      multifaceted ones when changing practice including tailored and targeted
      messaging. Multifaceted KT strategies led to changes in knowledge but not
      practice. Knowledge translation strategies shown to be less effective were
      passive and included access to registries of pre-processed research evidence or
      print materials. While knowledge brokering did not have a significant effect
      generally, results suggested that it did have a positive effect on those
      organizations that at baseline perceived their organization to place little value
      on evidence-informed decision making. CONCLUSIONS: No singular KT strategy was
      shown to be effective in all contexts. Conclusions about interventions cannot be
      taken on their own without considering the characteristics of the knowledge that
      was being transferred, providers, participants and organizations.

PMID- 22958372
TI  - Multifetal pregnancies: preterm admissions and outcomes.
AB  - OBJECTIVE: To describe the rates of antenatal hospital admission during twin or
      higher order multifetal pregnancies, and the admission outcomes as discharge
      undelivered, transfer to higher care, or spontaneous or elective delivery.
      METHODS: Cohort study using linked birth and hospital data. The cohort comprised
      women who gave birth to twins or higher order multiple infants of>=24 weeks
      gestation in 2001-2008 and who were admitted to hospital in weeks 20-36 of the
      pregnancy. RESULTS: In 63.4% of 10 779 twin pregnancies and 99.5% of 197 triplet
      and quadruplet pregnancies, the woman was admitted to hospital at least once in
      weeks 20-36 of the pregnancy, for a total 10 985 admissions. Almost half the
      admissions (46.3%) ended in discharge without delivery, 10.7% in transfer to
      higher care, 21.1% in spontaneous labour and birth, and 21.8% in elective
      delivery (induction or prelabour Caesarean section). The reason for admission was
      preterm labour in 34.2% of admissions. CONCLUSIONS: Hospital admission during
      pregnancy is common for women with multifetal pregnancies, with many of these
      admissions resulting in preterm birth. This is the first study to report the rate
      of pregnancy admissions for women with multifetal pregnancies, and provides a
      baseline for future studies of hospital use in this population.

PMID- 22958373
TI  - Parental phonological memory contributes to prediction of outcome of late talkers
      from 20 months to 4 years: a longitudinal study of precursors of specific
      language impairment.
AB  - BACKGROUND: Many children who are late talkers go on to develop normal language,
      but others go on to have longer-term language difficulties. In this study, we
      considered which factors were predictive of persistent problems in late talkers.
      METHODS: Parental report of expressive vocabulary at 18 months of age was used to
      select 26 late talkers and 70 average talkers, who were assessed for language and
      cognitive ability at 20 months of age. Follow-up at 4 years of age was carried
      out for 24 late and 58 average talkers. A psychometric test battery was used to
      categorize children in terms of language status (unimpaired or impaired) and
      nonverbal ability (normal range or more than 1 SD below average). The vocabulary
      and non-word repetition skills of the accompanying parent were also assessed.
      RESULTS: Among the late talkers, seven (29%) met our criteria for specific
      language impairment (SLI) at 4 years of age, and a further two (8%) had low
      nonverbal ability. In the group of average talkers, eight (14%) met the criteria
      for SLI at 4 years, and five other children (8%) had low nonverbal ability.
      Family history of language problems was slightly better than late-talker status
      as a predictor of SLI.. The best predictors of SLI at 20 months of age were score
      on the receptive language scale of the Mullen Scales of Early Learning and the
      parent's performance on a non-word repetition task. Maternal education was not a
      significant predictor of outcome. CONCLUSIONS: In this study, around three
      quarters of late talkers did not have any language difficulties at 4 years of
      age, provided there was no family history of language impairment. A family
      history of language-literacy problems was found to be a significant predictor for
      persisting problems. Nevertheless, there are children with SLI for whom
      prediction is difficult because they did not have early language delay.

PMID- 22958374
TI  - The effects of lighting conditions and food restriction paradigms on locomotor
      activity of common spiny mice, Acomys cahirinus.
AB  - BACKGROUND: An endogenous circadian clock controls locomotor activity in common
      spiny mice (Acomys cahirinus). However, little is known about the effects of
      constant light (LL) on this activity or about the existence of an additional food
      entrainable clock. A series of experiments were performed to investigate the
      effects of LL and DD on tau and activity levels. METHODS: Spiny mice were housed
      individually and their running wheel activity monitored. One group of mice was
      exposed to LD, DD and several intensities of LL. Another group was exposed to a
      restricted feeding (RF) paradigm in light: dark (LD) during one hour before the L
      to D transition. Significance of rhythmicity was assessed using Lomb-Scargle
      periodograms. RESULTS: In LD all animals exhibited nocturnal activity rhythms
      that persisted in DD. When animals were exposed to RF (during L), all of these
      animals (n = 11) demonstrated significant food anticipatory activity as well as
      an increase in diurnal activity. This increase in diurnal activity persisted in
      4/11 animals during subsequent ad libitum conditions. Under LL conditions, the
      locomotor rhythms of 2/11 animals appeared to entrain to RF. When animals were
      exposed to sequentially increasing LL intensities, rhythmicity persisted and,
      while activity decreased significantly, the free-running period was relatively
      unaffected. In addition, the period in LL was significantly longer than the
      period in DD. Exposure to LL also induced long-term changes (after-effects) on
      period and activity when animals were again exposed to DD. CONCLUSIONS: Overall
      these studies demonstrate clear and robust circadian rhythms of wheel-running in
      A. cahirinus. In addition, LL clearly inhibited activity in this species and
      induced after-effects. The results also confirm the presence of a food
      entrainable oscillator in this species.

PMID- 22958375
TI  - Characterization and ligand identification of a membrane progesterone receptor in
      fungi: existence of a novel PAQR in Sporothrix schenckii.
AB  - BACKGROUND: Adaptive responses in fungi result from the interaction of membrane
      receptors and extracellular ligands. Many different classes of receptors have
      been described in eukaryotic cells. Recently a new family of receptors classified
      as belonging to the progesterone-adiponectin receptor (PAQR) family has been
      identified. These receptors have the seven transmembrane domains characteristic
      of G-protein coupled receptors, but their activity has not been associated
      directly to G proteins. They share sequence similarity to the eubacterial
      hemolysin III proteins. RESULTS: A new receptor, SsPAQR1 (Sporothrix schenckii
      progesterone-adiponectinQ receptor1), was identified as interacting with
      Sporothrix schenckii G protein alpha subunit SSG-2 in a yeast two-hybrid assay.
      The receptor was identified as a member of the PAQR family. The cDNA sequence
      revealed a predicted ORF of 1542 bp encoding a 514 amino acids protein with a
      calculated molecular weight of 57.8 kDa. Protein domain analysis of SsPAQR1
      showed the 7 transmembrane domains (TM) characteristic of G protein coupled
      receptors and the presence of the distinctive motifs that characterize PAQRs. A
      yeast-based assay specific for PAQRs identified progesterone as the agonist. S.
      schenckii yeast cells exposed to progesterone (0.50 mM) showed an increase in
      intracellular levels of 3', 5' cyclic adenosine monophosphate (cAMP) within the
      first min of incubation with the hormone. Different progesterone concentrations
      were tested for their effect on the growth of the fungus. Cultures incubated at
      35 degrees C did not grow at concentrations of progesterone of 0.05 mM or higher.
      Cultures incubated at 25 degrees C grew at all concentrations tested (0.01 mM
      0.50 mM) with growth decreasing gradually with the increase in progesterone
      concentration. CONCLUSION: This work describes a receptor associated with a G
      protein alpha subunit in S. schenckii belonging to the PAQR family. Progesterone
      was identified as the ligand. Exposure to progesterone increased the levels of
      cAMP in fungal yeast cells within the first min of incubation suggesting the
      connection of this receptor to the cAMP signalling pathway. Progesterone
      inhibited the growth of both the yeast and mycelium forms of the fungus, with the
      yeast form being the most affected by the hormone.

PMID- 22958376
TI  - Evaluation of a sticky trap (AedesTraP), made from disposable plastic bottles, as
      a monitoring tool for Aedes aegypti populations.
AB  - BACKGROUND: Dengue virus, which is transmitted by Aedes aegypti mosquitoes is the
      most important emerging viral disease, infecting more than 50 million people
      annually. Currently used sticky traps are useful tools for monitoring and control
      of A. aegypti, despite differences in efficiency, labor requirements and cost. In
      the present work, a field assay was carried out to evaluate the performance of a
      sticky trap (AedesTrap), produced using disposable material, in capturing gravid
      Aedes spp. females. Additionally, conditions necessary for the improved
      performance of the device, such as number of traps per site and location (indoors
      or outdoors) were evaluated. METHODS: During a one year period, traps were placed
      in a dengue endemic area in 28 day cycles. The trap, named AedesTrap, consisted
      of a disposable plastic soda bottle coated inside with colophony resin, which
      served as a sticky substrate. Disposable bottles were donated by restaurants, and
      traps were made by laboratory staff, reducing the cost of the sticky trap (less
      than U$3). Mosquito capture in indoor and outdoor areas was compared by placing
      the traps in laundry room, kitchen or bedroom (indoors) and front or back yard
      (outdoors). The relationship between the number of AedesTraps and quantity of
      captured mosquitoes was investigated by utilizing one or three traps/site.
      RESULTS: During a 28 day cycle, a single AedesTrap was capable of capturing up to
      15 A. aegypti in a house, with a mean capture of 0.5 to 2.63 females per premise.
      The AedesTrap collected three times more outdoors versus indoors. Similarly, the
      capability of detecting Aedes spp. infestation, and of capturing females, was
      three times higher when using three AedesTraps per house, compared with one trap
      per house. CONCLUSIONS: AedesTrap was shown to be capable of capturing A. aegypti
      and other culicidae, providing information on the adult mosquito population, and
      allowing the identification of areas critically infested by mosquitoes. Low
      requirements for skilled labor together with easy maintenance and low cost are
      additional advantages of using this sticky trap.

PMID- 22958377
TI  - Children's Body composition and Stress - the ChiBS study: aims, design, methods,
      population and participation characteristics.
AB  - BACKGROUND: The last decades, the prevalence of childhood obesity has increased.
      Apart from other lifestyle factors, the effect of chronic psychosocial stress on
      the development of obesity has been recognized. However, more research is needed
      into the influence of chronic stress on appetite regulation, energy balance and
      body composition, as well as on the interaction with physical activity/sedentary
      behavior, diet and sleep in children. In this regard, the ChiBS study (Children's
      Body composition and Stress) was designed at the Ghent University. Within this
      paper, we describe the aims, design, methods, participation and population
      characteristics of the ChiBS study. METHODS: The influence of chronic stress on
      changes in body composition is investigated over a two-year follow-up period
      (February-June 2010, 2011 and 2012) in primary-school children between 6 and 12
      years old in the city Aalter (Flanders, Belgium).Stress is measured by child- and
      parent-reported stress-questionnaires, as well as by objective stress biomarkers
      (serum, salivary and hair cortisol) and heart rate variability. Body composition
      is evaluated using basic anthropometric measurements and air displacement
      plethysmography. Additional information on socio-economic status, medical
      history, physical activity, dietary intake and sleep are obtained by
      questionnaires, and physical activity by accelerometers. RESULTS: The
      participation percentage was 68.7% (N = 523/761), with 71.3% of the children
      willing to participate in the first follow-up survey. Drop-out proportions were
      highest for serum sampling (12.1%), salivary sampling (8.3%) and heart rate
      variability measurements (7.4%). DISCUSSION: The ChiBS project is unique in its
      setting: its standardized and longitudinal approach provides valuable data and
      new insights into the relationship between stress and changes in body composition
      in a large cohort of young children. In addition, this study allows an in-depth
      investigation of the validity of the different methods that were used to assess
      stress levels in children.

PMID- 22958378
TI  - Anxiety and depression in COPD.

PMID- 22958379
TI  - Daptomycin exposure precedes infection and/or colonization with daptomycin non
      susceptible enterococcus.
AB  - BACKGROUND: Daptomycin non-susceptible enterococci (DNSE) are emerging as an
      important cause of healthcare-associated infection, however little is known about
      the epidemiology of DNSE. At the University of Iowa Hospitals and Clinics (UIHC)
      an increase in the frequency of patients infected and/or colonized with DNSE has
      occurred. The goals of this study were to evaluate potential factors associated
      with the development of DNSE colonization and/or infection and to compare the
      characteristics of patients with prior daptomycin exposure to those without prior
      daptomycin exposure. METHODS: The study is a retrospective case-series involving
      all patients with DNSE infection and/or colonization at UIHC, a 734-bed academic
      referral center, from June 1, 2005 to June 1, 2011. RESULTS: The majority of
      patients with DNSE colonization and/or infection had prior daptomycin exposure
      (15 of 25; 60%), a concomitant gastrointestinal process (19 of 25; 76%), or were
      immunosuppressed (21 of 25; 84%). DNSE infection was confirmed in 17 of 25 (68%)
      patients, including 9 patients with bacteremia. Twelve of 17 (71%) patients with
      DNSE infection had prior daptomycin exposure, including 7 of 9 (78%) patients
      with bacteremia. Compared to patients without prior daptomycin exposure, patients
      with prior daptomycin exposure were less likely to harbor E. faecalis (0% vs.
      33%; p = 0.019). A high proportion of patients (10 of 25; 40%) died during their
      hospitalizations. Most enterococcal isolates were E. faecium (86%), and were
      vancomycin-resistant (72%). Molecular typing revealed a diverse population of
      DNSE. CONCLUSIONS: Prior daptomycin exposure, immunosuppression, and/or a
      concomitant gastrointestinal process, may be associated with the development of
      DNSE. PFGE revealed a diverse population of DNSE, which along with both
      increasing numbers of DNSE detected yearly and increasing annual rates of
      daptomycin usage, suggests the emergence of DNSE under antimicrobial pressure.

PMID- 22958380
TI  - Dyspnea: an update.

PMID- 22958381
TI  - A network meta-analysis to compare glycaemic control in patients with type 2
      diabetes treated with exenatide once weekly or liraglutide once daily in
      comparison with insulin glargine, exenatide twice daily or placebo.
AB  - AIMS: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide once
      weekly (ExQW) and liraglutide once daily (QD) are indicated to improve glycaemic
      control in patients with type 2 diabetes. Although glycaemic control with ExQW
      versus liraglutide QD 1.8 mg has been directly compared, no studies have compared
      ExQW with liraglutide QD 1.2 mg or determined the probable relative efficacies of
      various injectable therapies for glycaemic control; therefore, a network meta
      analysis was performed to address these questions. METHODS: A systematic review
      identified randomized controlled trials of >=24 weeks that compared ExQW,
      liraglutide QD (1.2 mg, 1.8 mg), insulin glargine, exenatide twice daily (ExBID),
      or placebo. Twenty-two studies evaluating 11 049 patients were included in the
      network meta-analysis. Mean differences in HbA1c relative to placebo or each
      other and probability rankings were estimated. RESULTS: Estimated mean
      differences in HbA1c versus placebo were -1.15% (95% CrI: -1.31 to -1.00) for
      ExQW, -1.01% (95% CrI: -1.18 to -0.85) for liraglutide 1.2 mg, and -1.18% (95%
      CrI: -1.32 to -1.04) for liraglutide 1.8 mg. HbA1c differences for ExQW versus
      liraglutide 1.2 mg and 1.8 mg were -0.14% (95% CrI: -0.34 to 0.06) and 0.03% (95%
      CrI: -0.14 to 0.18), respectively. The estimated mean difference in HbA1c between
      liraglutide 1.2 mg and 1.8 mg was 0.17% (95% CrI: 0.02-0.30). Results were
      consistent when adjusted for background antihyperglycaemic medications and
      diabetes duration. CONCLUSIONS: This network meta-analysis did not identify
      meaningful differences in HbA1c lowering between ExQW and both liraglutide doses,
      suggesting that these GLP-1 RAs have similar glycaemic effects.

PMID- 22958383
TI  - Novel iron-regulated and Fur-regulated small regulatory RNAs in Aggregatibacter
      actinomycetemcomitans.
AB  - Iron can regulate biofilm formation via non-coding small RNA (sRNA). To determine
      if iron-regulated sRNAs are involved in biofilm formation by the
      periodontopathogen Aggregatibacter actinomycetemcomitans, total RNA was isolated
      from bacteria cultured with iron supplementation or chelation. Transcriptional
      analysis demonstrated that the expression of four sRNA molecules (JA01-JA04)
      identified by bioinformatics was significantly upregulated in iron-limited medium
      compared with iron-rich medium. A DNA fragment encoding each sRNA promoter was
      able to titrate Escherichia coli ferric uptake regulator (Fur) from a Fur
      repressible reporter fusion in an iron uptake regulator titration assay. Cell
      lysates containing recombinant AaFur shifted the mobility of sRNA-specific DNAs
      in a gel shift assay. Potential targets of these sRNAs, determined in silico,
      included genes involved in biofilm formation. The A. actinomycetemcomitans
      overexpressing JA03 sRNA maintained a rough phenotype on agar, but no longer
      adhered to uncoated polystyrene or glass, although biofilm determinant gene
      expression was only modestly decreased. In summary, these sRNAs have the ability
      to modulate biofilm formation, but their functional target genes remain to be
      confirmed.

PMID- 22958384
TI  - Molecular approaches for viable bacterial population and transcriptional analyses
      in a rodent model of dental caries.
AB  - Culturing methods are the primary approach for microbiological analysis of plaque
      biofilms in rodent models of dental caries. In this study, we developed
      strategies for the isolation of DNA and RNA from plaque biofilms formed in vivo
      to analyse the viable bacterial population and gene expression. Plaque biofilm
      samples from rats were treated with propidium monoazide to isolate DNA from
      viable cells, and the purified DNA was used to quantify total bacteria and the
      Streptococcus mutans population via quantitative polymerase chain reaction (qPCR)
      and specific primers; the same samples were also analysed by counting colony
      forming units (CFU). In parallel, RNA was isolated from plaque-biofilm samples
      (from the same animals) and used for transcriptional analyses via reverse
      transcription-qPCR. The viable populations of both S. mutans and total bacteria
      assessed by qPCR were positively correlated with the CFU data (P < 0.001; r >
      0.8). However, the qPCR data showed higher bacterial cell counts, particularly
      for total bacteria (vs. CFU). Moreover, S. mutans proportion in the plaque
      biofilm determined by qPCR analysis showed strong correlation with incidence of
      smooth-surface caries (P = 0.0022, r = 0.71). The purified RNAs presented high
      RNA integrity numbers (> 7), which allowed measurement of the expression of genes
      that are critical for S. mutans virulence (e.g. gtfB and gtfC). Our data show
      that the viable microbial population and the gene expression can be analysed
      simultaneously, providing a global assessment of the infectious aspect of dental
      caries. Our approach could enhance the value of the current rodent model in
      further understanding the pathophysiology of this disease and facilitating the
      exploration of novel anti-caries therapies.

PMID- 22958385
TI  - Salivary proteins promote proteolytic activity in Streptococcus mitis biovar 2
      and Streptococcus mutans.
AB  - A major function of the salivary pellicle on oral surfaces is to promote
      colonization of the commensal microbiota by providing binding sites for
      adherence. Streptococcus mitis is an early colonizer of the oral cavity whereas
      Streptococcus mutans represents a later colonizer. To survive and grow, oral
      bacteria produce enzymes, proteases and glycosidases, which allow them to exploit
      salivary proteins as a nutrient source. In this study, adherence and proteolytic
      activity of S. mitis biovar 2 and S. mutans were investigated in a flow-cell
      model in the presence of different populations of surface-associated salivary
      proteins. Streptococcus mitis biovar 2 adhered well to surfaces coated with both
      a MUC5B-enriched fraction and a pool of low-density proteins containing MUC7,
      amylase, cystatin, gp340, immunoglobulin A, lactoferrin, lysozyme and statherin,
      whereas adherence of S. mutans to these proteins was poor. In environments of
      MUC5B or the low-density proteins, both S. mitis biovar 2 and S. mutans showed
      high levels of proteolytic activity. For S. mitis in the MUC5B environment, most
      of this activity may be attributable to contact with the molecules in the fluid
      phase although activity was also enhanced by adherence to surface-associated
      MUC5B. These data suggest that although they differ in their capacity to adhere
      to surface-associated salivary proteins, in the natural environment exploitation
      of saliva as a nutrient source can contribute to survival and colonization of the
      oral cavity by both S. mitis biovar 2 and S. mutans.

PMID- 22958386
TI  - Toll-like receptor 4 mediates intrauterine growth restriction after systemic
      Campylobacter rectus infection in mice.
AB  - Campylobacter rectus is associated with fetal exposure and low birthweight in
      humans. C. rectus also invades placental tissues and induces fetal intrauterine
      growth restriction (IUGR) in mice, along with overexpression of Toll-like
      receptors (TLR4), suggesting that TLR4 may mediate placental immunity and IUGR in
      mice. To test this hypothesis we examined the effect of in vitro TLR4
      neutralization on trophoblastic proinflammatory activity and studied the IUGR
      phenotype in a congenic TLR4-mutant mouse strain after in vivo C. rectus
      infection. Human trophoblasts were pretreated with TLR4 neutralizing antibodies
      and infected with C. rectus; proinflammatory cytokine production was assessed by
      cytokine multiplex assays. Neutralizing TLR4 antibodies significantly impaired
      the production of proinflammatory cytokines in trophoblastic cells after
      infection in a dose-dependent manner. We used a subcutaneous chamber model to
      provide a C. rectus challenge in BALB/cAnPt (TLR4(Lps-d) ) and wild-type (WT)
      females. Females were mated with WT or TLR4(Lps-d) males once/week; pregnant mice
      were infected at (E)7.5 and sacrificed at (E)16.5 to establish IUGR phenotypes.
      Maternal C. rectus infection significantly decreased fetal weight/length in
      infected WT when compared with sham WT controls (P < 0.05, analysis of variance).
      However, infected TLR4(Lps-d -/-) mice did not show statistically significant
      differences in fetal weight and length when compared with WT controls (P > 0.05).
      Furthermore, heterozygous TLR4(Lps-d +/-) fetuses showed IUGR phenotype rescue.
      We conclude that TLR4 is an important mediator of trophoblastic proinflammatory
      responses and TLR4-deficient fetuses do not develop IUGR phenotypes after C.
      rectus infection, suggesting that placental cytokine activation is likely to be
      mediated by TLR4 during low birthweight/preterm birth pathogenesis.

PMID- 22958387
TI  - Characterization of the secretion pathway of the collagen adhesin EmaA of
      Aggregatibacter actinomycetemcomitans.
AB  - The extracellular matrix protein adhesin A (EmaA) surface antennae-like
      structures of the periodontal pathogen Aggregatibacter actinomycetemcomitans are
      composed of three identical protein monomers. Recently, we have demonstrated that
      the protein is synthesized with an extended signal peptide of 56 amino acids
      necessary for membrane targeting and protein translocation. In this study, EmaA
      secretion was demonstrated to be reliant on a chaperone-dependent secretion
      pathway. Deletion of secB partially reduced but did not abolish the amount of
      EmaA in the membrane. This observation was attributed to an increase in the
      synthesis of DnaK in the DeltasecB strain. Overexpression of a DnaK substitution
      mutant (A174T), with diminished activity, in the DeltasecB strain further reduced
      the amount of EmaA in the membrane. Expression of dnaK A174T in the wild-type
      strain did not affect the amount of EmaA in the membrane when grown under optimal
      growth conditions at 37 degrees C. However, EmaA was found to be reduced when
      this strain was grown at heat-shock temperature. A chromosomal deletion of amino
      acids 16-39 of the EmaA extended signal peptide, transformed with either the wild
      type or dnaK A174T-expressing plasmid, did not affect the amount of EmaA in the
      membrane. In addition, the level of EmaA in a DeltasecB/emaA(-) double mutant
      strain expressing EmaADelta16-39 was unchanged when grown at both temperatures.
      The data suggest that chaperones are required for the targeting of EmaA to the
      membrane and a specific region of the signal peptide is necessary for secretion
      under stress conditions.

PMID- 22958389
TI  - Synthesis of nonionic-anionic colloidal systems based on alkaline and ammonium
      beta-nonylphenol polyethyleneoxy (n = 3-20) propionates/dodecylbenzenesulfonates
      with prospects for food hygiene.
AB  - BACKGROUND: The main objective of this work was to obtain a binary system of
      surface-active components (nonionic soap - alkaline and/or ammonium
      dodecylbenzenesulfonate) with potential competences in food hygiene, by accessing
      a scheme of classical reactions (cyanoethylation, total acid hydrolysis and
      stoichiometric neutralization with inorganic alkaline and/or organic ammonium
      bases) adapted to heterogeneously polyethoxylated nonylphenols (n = 3-20). In the
      processing system mentioned, dodecylbenzenesulfonic acid, initially the acid
      catalyst for the exhaustive hydrolysis of beta-nonylphenolpolyethyleneoxy (n = 3
      20) propionitriles, becomes together with the nonionic soap formed the second
      surface-active component of the binary system. RESULTS: In the reaction scheme
      adopted the influence of the main operating (duration, temperature, molar ratio
      of reagents) and structural parameters (degree of oligomerization of the
      polyoxyethylene chain) on the processing yields for the synthetic steps was
      followed. The favorable role of the polyoxyethylene chain size is remarked,
      through its specific conformation and its alkaline cations sequestration
      competences on the yields of cyanoethylation, but also the beneficial influence
      of phase-transfer catalysts in the total acid hydrolysis step. The chemical
      stability of dodecylbenzenesulfonic acid (DBSH) at the temperature and strongly
      acidic pH of the reaction environment is confirmed. The controlled change of the
      amount of DBSH in the final binary system will later confer it potential
      colloidal competences in food hygiene receipts. CONCLUSIONS: The preliminary
      synthetic tests performed confirmed the prospect of obtaining a broad range of
      useful colloidal competences in various food hygiene scenarios.

PMID- 22958388
TI  - Sustained mitogen-activated protein kinase activation with Aggregatibacter
      actinomycetemcomitans causes inflammatory bone loss.
AB  - Aggregatibacter actinomycetemcomitans is a gram-negative facultative capnophile
      involved in pathogenesis of aggressive forms of periodontal disease. In the
      present study, we interrogated the ability of A. actinomycetemcomitans to
      stimulate innate immune signaling and cytokine production and established that A.
      actinomycetemcomitans causes bone loss in a novel rat calvarial model. In vitro
      studies indicated that A. actinomycetemcomitans stimulated considerable
      production of soluble cytokines, tumor necrosis factor-alpha, interleukin-6 and
      interleukin-10 in both primary bone marrow-derived macrophages and NR8383
      macrophages. Immunoblot analysis indicated that A. actinomycetemcomitans exhibits
      sustained activation of all major mitogen-activated protein kinase (MAPK)
      pathways, as well as the negative regulator of MAPK signaling, MAPK phosphatase-1
      (MKP-1), for at least 8 h. In a rat calvarial model of inflammatory bone loss,
      high and low doses of formalin-fixed A. actinomycetemcomitans were microinjected
      into the supraperiosteal calvarial space for 1-2 weeks. Histological staining and
      micro-computed tomography of rat calvariae revealed a significant increase of
      inflammatory and fibroblast infiltrate and increased bone resorption as measured
      by total lacunar pit formation. From these data, we provide new evidence that
      fixed whole cell A. actinomycetemcomitans stimulation elicits a pro-inflammatory
      host response through sustained MAPK signaling, leading to enhanced bone
      resorption within the rat calvarial bone.

PMID- 22958390
TI  - COPD a social disease: inappropriateness and pharmaco-economics. The role of the
      specialist: present and future.

PMID- 22958391
TI  - Fairness of utilizing health care facilities and out-of-pocket payment burden:
      evidence from Cambodia.
AB  - Catastrophic spending on health care through out-of-pocket payment is a huge
      problem in most low- and middle-income countries all over the world. The collapse
      of health systems and poverty have resulted in the proliferation of the private
      health sector in Cambodia, but very few studies have examined the fairness in
      ease of utilization of these services based on mode of payment. This study
      examined the utilization of health services for sickness or injury and identified
      its relationship with people's ability to pay for treatment seeking at various
      instances. Based on cross-sectional data from the Cambodian 2007 Demographic and
      Health Survey, the economic index estimated through principal component analysis
      and Lorenz curve was used to quantify the degree of fairness and equality in
      utilization and payment burden among the respondents. A distinct level of
      fairness was found in health care utilization and out-of-pocket payments.
      Specifically, use of private health care facilities and over-the-counter remedies
      dominate, and out-of-pocket payments cut across all socioeconomic strata. As many
      countries in low- and middle-income regions, and most importantly those in
      transition such as Cambodia, are repositioning their health systems, efforts
      should be made towards maintaining equitable access through adoption of finance
      mechanisms that make utilization of health care services fair and equitable.

PMID- 22958392
TI  - Evaluation of pharmacotherapy of obstructive airway diseases in the Montenegrin
      outpatient care: comparison with two Scandinavian countries.
AB  - BACKGROUND: This study is aimed at evaluating the pharmacotherapy of obstructive
      airway diseases (OAD) in the Montenegrin outpatient care (MOC) in 2010. METHODS:
      Data on the reimbursed drugs which were prescribed during the reference period
      were obtained from the National Database that was established within the Health
      Insurance Fund of Montenegro in 2004. We have applied the standard
      pharmacoepidemiologic methodology with the defined daily dose (DDD) along with
      the Anatomical Therapeutic Chemical (ATC) classification of drugs. Clinical
      entities of OAD were classified according to the International Classification of
      Diseases (ICD-Revision X). RESULTS: Prescribing and the subsequent use of drugs
      for OAD (ATC code R03) in 2010 was 18.18 DDD/1000inhabitants/day, much lower than
      in some developed countries. Fenoterol/ipratropium and salmeterol/fluticasone
      fixed combinations had the highest utilisation level, accounting for more than
      50% of all OAD drugs. About 90% of OAD drugs were prescribed for COPD and asthma.
      CONCLUSIONS: Obtained results indicate that there are still large differences in
      OAD drug utilisation in MOC when compared with developed countries, but also some
      improvement in pharmacological approach to the pharmacotherapy of OAD in
      comparison to the earlier period.

PMID- 22958393
TI  - Species diversity within a community of the curcurbit fruit flies Bactrocera
      cucurbitae, Dacus ciliatus, and Dacus demmerezi roosting in corn borders near
      cucurbit production areas of Reunion Island.
AB  - In order to better control fruit flies (Diptera: Tephritidae) attacking
      Cucurbitaceae on Reunion Island (21 degrees 6 S/ 55 degrees 36 E), biological
      characteristics (seasonal fluctuation, relative abundance, sex ratio) of
      communities roosting in corn borders were investigated. The study was conducted
      in austral summer across a range of altitudes (750-1150 m) corresponding to the
      main areas of cucurbit cropping. Living adults were recorded roosting on corn
      planted within or around cucurbit fields. Results showed a high variability in
      seasonal fluctuation of populations according to local conditions. Bactrocera
      Cucurbitae (Coquillett) (Diptera: Tephritidae) was the least abundant species
      (27%) compared to Dacus ciliatus Loew (36%) and Dacus demmerezi Bezzi (37%).
      Relative abundance of B. Cucurbitae was lowest (< 18%) in high altitude sites
      (above 1000 m), where D. demmerezi was the most prevalent species (> 56%). Dacus
      ciliatus showed variable relative abundance (from 18 to 51%) depending on the
      experimental design (varying in location and in year). Sex ratio was also very
      variable from one species to another and from one experimental design to another.

PMID- 22958394
TI  - Nutritional status and dietary intake of urban residents in Gondar, Northwest
      Ethiopia.
AB  - BACKGROUND: There is paucity of data on the dietary intake and nutritional status
      of urban Ethiopians which necessitates comprehensive nutritional assessments.
      Therefore, the present study was aimed at evaluating the dietary intake and
      nutritional status of urban residents in Northwest Ethiopia. METHODS: This cross
      sectional community based nutrition survey was conducted by involving 356
      participants (71.3% female and 28.7% male with mean age of 37.3 years). Subjects
      were selected by random sampling. Socio demographic data was collected by
      questionnaire. Height, weight, hip circumference and waist circumference were
      measured following standard procedures. Dietary intake was assessed by a food
      frequency questionnaire and 24-h dietary recall. The recommended dietary
      allowance was taken as the cut-off point for the assessment of the adequacy of
      individual nutrient intake. RESULTS: Undernourished, overweight and obese
      subjects composed 12.9%, 21.3% and 5.9% of the participants, respectively. Men
      were taller, heavier and had higher waist to hip ratio compared to women (P <
      0.05). Fish, fruits and vegetables were consumed less frequently or never at all
      by a large proportion of the subjects. Oil and butter were eaten daily by most of
      the participants. Mean energy intakes fell below the estimated energy
      requirements in women (1929 vs 2031 kcal/day, P = 0.05) while it was
      significantly higher in men participants (3001 vs 2510 kcal/day, P = 0.007).
      Protein intake was inadequate (<0.8 g/kg/day) in 11.2% of the participants
      whereas only 2.8% reported carbohydrate intake below the recommended dietary
      allowances (130 g/day). Inadequate intakes of calcium, retinol, thiamin,
      riboflavin, niacin and ascorbic acid were seen in 90.4%, 100%, 73%, 92.4%, 86.2%
      and 95.5% of the participants. CONCLUSIONS: The overall risk of nutritional
      inadequacy among the study participants was high along with their poor dietary
      intake. Hence, more stress should be made on planning and implementing
      nutritional programmes in urban settings aimed at preventing or correcting
      micronutrient and some macronutrient deficiencies which may be useful in
      preventing nutrition related diseases in life.

PMID- 22958395
TI  - In Vitro assessment of the nutritive value of expanded soybean meal for dairy
      cattle.
AB  - Little information is available about the nutritive value of expanded soybean
      meal, which is produced by expansion of soybeans prior to solvent extraction of
      the oil. During processing, expanded soybean meal is subjected to additional
      heat, which might increase the concentration of ruminally undegraded protein.
      Processing of soybeans with heat during oil extraction could affect lysine
      availability by increasing ruminally undegraded protein or by impairing
      intestinal digestion. Our objective was to compare solvent and expanded soybeans
      with regard to chemical composition and nutritive value for dairy cattle. Samples
      of expanded soybean meal (n = 14) and solvent-extracted soybean meal (n = 5) were
      obtained from People's Republic of China to study effects of the expansion
      process on nutritive value for dairy cattle. Solvent-extracted soybean meal (n =
      2) and mechanically extracted (heated) soybean meal (n = 2) from the United
      States served as references for comparison. Samples were analyzed for crude fat,
      long-chain fatty acids, crude protein, amino acids, chemically available lysine,
      in situ ruminal protein degradation, and in vitro intestinal digestibility. No
      differences were found between solvent-extracted soybean meals from China and
      expanded soybean meals from China for crude fat, crude protein, amino acids, or
      chemically available lysine. In situ disappearance of nitrogen, ruminally
      undegraded protein content, and in vitro intestinal digestion of the ruminally
      undegraded protein were generally similar between solvent-extracted soybean meals
      made in China and expanded soybean meals made in China; variation among soybean
      meals was small. Results indicate that the additional heat from the expansion
      process was not great enough to affect the nutritive value of soybean meal
      protein for ruminants. Although expansion may improve the oil extraction process,
      the impact on the resulting soybean meal is minimal and does not require
      consideration when formulating ruminant diets.

PMID- 22958396
TI  - Factors associated with hospital admission in patients reaching the emergency
      department with COPD exacerbation.
AB  - BACKGROUND: The aim of this study was to determine the frequency of COPD
      exacerbations in our Emergency Department, as well as the hospitalization-related
      factors. METHODS: Prospective observational study conducted in the Emergency
      Department of Salnes County Hospital among patients admitted for COPD
      exacerbation. Admission predictors were determined by multivariate analysis.
      RESULTS: There were 409 exacerbations in 239 patients (79% male, mean age 75).
      57% of exacerbations required hospitalization. Hospitalization-related factors
      were impaired oxygenation (p < 0.001), presence of neutrophilia (p < 0.01) and
      prescription of antibiotics in the Emergency Department (p < 0.05). CONCLUSIONS:
      COPD exacerbation accounts for over 1% of all visits to our Emergency Department.
      57% of them required hospitalization. Impaired oxygenation, greater neutrophilia
      and prescription of antibiotics in the Emergency Department were associated with
      greater probability of admission.

PMID- 22958397
TI  - Potent melanin production enhancement of human tyrosinase gene by Tat and an
      entrapment in elastic cationic niosomes: potential application in vitiligo gene
      therapy.
AB  - Potent melanin production enhancement of human tyrosinase plasmid (pAH7/Tyr, P)
      in mouse melanoma cells (B(16)F(10)) by Tat peptide (T) and an entrapment in
      elastic cationic niosomes (E) was described. The E composed of Tween
      61/cholesterol/dodecyl dimethyl ammonium bromide at 1:1:0.5 molar ratio was
      prepared by freeze-dried emptying liposomes method. PE at P/E ratio of 1:160 w/w
      and TPE at T/P/E ratio of 0.125:1:160, 0.25:1:160, and 0.5:1:160 w/w/w were
      prepared. The final concentration of the plasmid in the study was 4 ng/MUL. By
      sulforhodamine B assay, PE and TPE complexes showed slight or no cytotoxic
      effect. The cells transfected with TPE (0.5:1:160) exhibited the highest
      enhancement of tyrosinase enzyme activity of 11.82-, 7.67-, 5.07-, and 6.29-folds
      of control, P, PE, and TP (0.5:1) and melanin production of 13.03-, 8.46-, 5.36-,
      and 6.58-folds of control, P, PE, and TP (0.5:1), respectively. The elastic
      cationic niosomes demonstrated an increase in thermal stability of P at 4 +/- 2,
      25 +/- 2, and 45 +/- 2  degrees C. The vesicular size and the zeta potential
      values of PE and TPE complexes were slightly increased but still in the range of
      stable dispersion (out of +/-30 mV). These results indicated the high potential
      application of the TPE complexes for further investigation for vitiligo gene
      therapy.

PMID- 22958398
TI  - The pattern of injury and poisoning in South East Iran.
AB  - BACKGROUND: Injury is a leading cause of morbidity and mortality worldwide, and
      even more so in low and middle-income countries (LMICs). Iran is a LMIC and lacks
      information regarding injury for program and policy purposes. This study aimed to
      describe the incidence and patterns of injury in one province in South Eastern
      Iran. METHODS: A hospital-based, retrospective case review using a routinely
      collected registry in all Emergency Departments in Sistan and Baluchistan
      province, Iran for 12 months in 2007-2008. RESULTS: In total 18,155 injuries were
      recorded during the study period. The majority of injuries in South Eastern Iran
      were due to road traffic crashes. Individuals living in urban areas sustained
      more injuries compared to individuals from rural areas. Males typically
      experienced more injuries than females. Males were most likely to be injured in a
      street/alley or village whereas females were most likely to be injured in or
      around the home. In urban areas, road traffic related injuries were observed to
      affect older age groups more than younger age groups. Poisoning was most common
      in the youngest age group, 0 to 4 years. CONCLUSIONS: This study provides data on
      incidence and patterns of injury in South Eastern Iran. Knowledge of injury
      burden, such as this paper, is likely to help policy makers and planners with
      health service planning and injury prevention.

PMID- 22958399
TI  - Tigecycline challenge triggers sRNA production in Salmonella enterica serovar
      Typhimurium.
AB  - BACKGROUND: Bacteria employ complex transcriptional networks involving multiple
      genes in response to stress, which is not limited to gene and protein networks
      but now includes small RNAs (sRNAs). These regulatory RNA molecules are
      increasingly shown to be able to initiate regulatory cascades and modulate the
      expression of multiple genes that are involved in or required for survival under
      environmental challenge. Despite mounting evidence for the importance of sRNAs in
      stress response, their role upon antibiotic exposure remains unknown. In this
      study, we sought to determine firstly, whether differential expression of sRNAs
      occurs upon antibiotic exposure and secondly, whether these sRNAs could be
      attributed to microbial tolerance to antibiotics. RESULTS: A small scale sRNA
      cloning strategy of Salmonella enterica serovar Typhimurium SL1344 challenged
      with half the minimal inhibitory concentration of tigecycline identified four
      sRNAs (sYJ5, sYJ20, sYJ75 and sYJ118) which were reproducibly upregulated in the
      presence of either tigecycline or tetracycline. The coding sequences of the four
      sRNAs were found to be conserved across a number of species. Genome analysis
      found that sYJ5 and sYJ118 mapped between the 16S and 23S rRNA encoding genes.
      sYJ20 (also known as SroA) is encoded upstream of the tbpAyabKyabJ operon and is
      classed as a riboswitch, whilst its role in antibiotic stress-response appears
      independent of its riboswitch function. sYJ75 is encoded between genes that are
      involved in enterobactin transport and metabolism. Additionally we find that the
      genetic deletion of sYJ20 rendered a reduced viability phenotype in the presence
      of tigecycline, which was recovered when complemented. The upregulation of some
      of these sRNAs were also observed when S. Typhimurium was challenged by
      ampicillin (sYJ5, 75 and 118); or when Klebsiella pneumoniae was challenged by
      tigecycline (sYJ20 and 118). CONCLUSIONS: Small RNAs are overexpressed as a
      result of antibiotic exposure in S. Typhimurium where the same molecules are
      upregulated in a related species or after exposure to different antibiotics.
      sYJ20, a riboswitch, appears to possess a trans-regulatory sRNA role in
      antibiotic tolerance. These findings imply that the sRNA mediated response is a
      component of the bacterial response to antibiotic challenge.

PMID- 22958400
TI  - Morphology, sex ratio and gene expression of day 14 in vivo and in vitro bovine
      embryos.
AB  - The present study was designed to compare Day 14 bovine embryos that were
      produced entirely in vitro using the post-hatching development (PHD) system with
      in vivo-derived embryos without or with transient PHD culture from Day 7 to Day
      14. Embryos on Day 14 were used for sex determination and gene expression
      analysis of PLAC8, KRT8, CD9, SLC2A1, SLC2A3, PGK1, HSF1, MNSOD, HSP70 and IFNT
      using real-time quantitative (q) polymerase chain reaction (PCR). First, Day 7 in
      vivo- and in vitro-produced embryos were subjected to the PHD system. A higher
      rate of survival was observed for in vitro embryos on Day 14. Comparing Day 14
      embryos produced completely in vivo or completely in vitro revealed that the mean
      size of the former group was greater than that of the latter (10.29+/-1.83 vs
      2.68+/-0.33mm, respectively). Expression of the HSP70 and SLC2A1 genes was down-
      and upregulated, respectively, in the in vitro embryos. The present study shows
      that in vitro embryos cultured in the PHD system are smaller than in vivo embryos
      and that of the 10 genes analysed, only two were differentially expressed between
      the two groups. These findings indicate that, owing to the poor survival rate,
      the PHD system is not reliable for evaluation of in vitro embryo quality.

PMID- 22958401
TI  - Mechanism of nitrogen metabolism-related parameters and enzyme activities in the
      pathophysiology of autism.
AB  - BACKGROUND: There is evidence that impaired metabolism play an important role in
      the etiology of many neuropsychiatric disorders. Although this has not been
      investigated to date, several recent studies proposed that nitrogen metabolism
      related parameters may have a pathophysiological role in autism. METHODS: The
      study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy
      controls matched for age and gender. Levels of creatine, urea, ammonia, gamma
      aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic
      activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase
      (ADA) were determined in plasma samples from both groups. RESULTS: We found a
      significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a
      significant decrease in the enzymatic activity of ADA and glutamine level in
      patients with autism compared with healthy controls. The most significant
      variation between the two groups was found in the Glu:Gln ratio. CONCLUSION: A
      raised Glu:Gln ratio together with positive correlations in creatine, GABA, and
      5'-nucleotidase levels could contribute to the pathophysiology of autism, and
      might be useful diagnostic markers. The mechanism through which these parameters
      might be related to autism is discussed in detail.

PMID- 22958402
TI  - Bovine fasciolosis at increasing altitudes: parasitological and malacological
      sampling on the slopes of Mount Elgon, Uganda.
AB  - BACKGROUND: To clarify the extent and putative transmission zone of bovine
      fasciolosis on the slopes of Mount Elgon, Uganda, conjoint parasitological and
      malacological surveys, inclusive of inspection of animals at slaughter, were
      undertaken at increasing altitudes. RESULTS: A total of 239 cattle were sampled
      across eight locations ranging in elevation from 1112-2072 m. Faecal material was
      examined for presence of Fasciola eggs and sera were tested by ELISA for
      antibodies against Fasciola antigens. Bolstering this, 38 cattle at slaughter
      from 2 abattoir sites at 1150 m and 1947 m were inspected; in addition, wild
      buffalo stool (n=10) opportunistically picked within Mount Elgon National Park
      (MENP) at 3640 m was examined. By faecal egg detection, prevalence of Fasciola
      gigantica at low (<1500 m) and high (>1500 m) altitude sites was 43.7% (95% CI
      35.4-52.2) and 1.1% (95% CI 0.0-6.0), respectively, while by ELISA was much
      higher, low altitude--77.9% (95% CI 69.7-85.4) and high altitude--64.5% (95% CI
      51.3-76.3). The decline in prevalence with increasing altitude was corroborated
      by abattoir sampling. Thirty seven aquatic habitats, ranging from 1139-3937 m in
      altitude were inspected for freshwater snails, 12 of which were within MENP. At
      lower altitudes, Lymnaea (Radix) natalensis was common, and often abundant, but
      at higher altitudes became much rarer ceasing to be found above 1800 m. On the
      other hand, Lymnaea (Galba) truncatula was found only at altitudes above 3000 m
      and within MENP alone. The snail identifications were confirmed by DNA analysis
      of the ribosomal 18S gene. CONCLUSIONS: Active infections of F. gigantica in
      cattle are common in lower altitude settings but appear to diminish with
      increasing elevation. This is likely due to a growing paucity of intermediate
      hosts, specifically populations of L. natalensis for which a natural boundary of
      1800 m appeared. Although F. hepatica was not encountered, the presence of
      several populations of L. truncatula at elevations over 3000 m point towards a
      potential transmission zone within MENP should this parasite be introduced.

PMID- 22958403
TI  - Transforming growth factor beta1 inhibits bone morphogenic protein (BMP)-2 and
      BMP-7 signaling via upregulation of Ski-related novel protein N (SnoN): possible
      mechanism for the failure of BMP therapy?
AB  - BACKGROUND: Bone morphogenic proteins (BMPs) play a key role in bone formation.
      Consequently, it was expected that topical application of recombinant human
      (rh)BMP-2 and rhBMP-7 would improve the healing of complex fractures. However, up
      to 36% of fracture patients do not respond to this therapy. There are hints that
      a systemic increase in transforming growth factor beta1 (TGFbeta1) interferes
      with beneficial BMP effects. Therefore, in the present work we investigated the
      influence of rhTGFbeta1 on rhBMP signaling in primary human osteoblasts, with the
      aim of more specifically delineating the underlying regulatory mechanisms.
      METHODS: BMP signaling was detected by adenoviral Smad-binding-element-reporter
      assays. Gene expression was determined by reverse transcription polymerase chain
      reaction (RT-PCR) and confirmed at the protein level by western blot. Histone
      deacetylase (HDAC) activity was determined using a test kit. Data sets were
      compared by one-way analysis of variance. RESULTS: Our findings showed that
      Smad1/5/8-mediated rhBMP-2 and rhBMP-7 signaling is completely blocked by
      rhTGFbeta1. We then investigated expression levels of genes involved in BMP
      signaling and regulation (for example, Smad1/5/8, TGFbeta receptors type I and
      II, noggin, sclerostin, BMP and activin receptor membrane bound inhibitor
      (BAMBI), v-ski sarcoma viral oncogene homolog (Ski), Ski-related novel protein N
      (SnoN) and Smad ubiquitination regulatory factors (Smurfs)) and confirmed the
      expression of regulated genes at the protein level. Smad7 and SnoN were
      significantly induced by rhTGFbeta1 treatment while expression of Smad1, Smad6,
      TGFbetaRII and activin receptor-like kinase 1 (Alk1) was reduced. Elevated SnoN
      expression was accompanied by increased HDAC activity. Addition of an HDAC
      inhibitor, namely valproic acid, fully abolished the inhibitory effect of
      rhTGFbeta1 on rhBMP-2 and rhBMP-7 signaling. CONCLUSIONS: rhTGFbeta1 effectively
      blocks rhBMP signaling in osteoblasts. As possible mechanism, we postulate an
      induction of SnoN that increases HDAC activity and thereby reduces the expression
      of factors required for efficient BMP signaling. Thus, inhibition of HDAC
      activity may support bone healing during rhBMP therapy in patients with elevated
      TGFbeta serum levels.

PMID- 22958404
TI  - KH902 suppresses high glucose-induced migration and sprouting of human retinal
      endothelial cells by blocking VEGF and PIGF.
AB  - AIMS: Vascular endothelial growth factor (VEGF) and placental growth factor
      (PlGF) are upregulated in many ocular neovascular diseases such as diabetic
      retinopathy (DR). KH902 is a recombinant fusion protein with its binding ligand
      taken from the domains of VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2)
      and can bind all VEGF-A isoforms and PlGF. The aim of this study was to
      investigate the underlying mechanisms of anti-angiogenic effects of KH902.
      METHODS: The toxic effect of KH902 on cultured human retinal endothelial cells
      (HRECs) was measured by Annexin V/PI staining and MTT assay. The concentrations
      of secreted VEGF and PlGF were measured by ELISA. The migration of HRECs was
      assessed by scratch wound and transwell assay. The sprouting of HRECs was
      determined by tube formation assay. The protein levels of Src, p-Src, PI3K, Akt1,
      p-Akt1, Erk1/2 and p-Erk1/2 were measured by Western blot. RESULTS: KH902 at the
      concentrations from 100 ng/ml to 100 ug/ml had no cytotoxicity to cultured HRECs.
      KH902 bound not only VEGF165, but also PlGF that were secreted by HRECs under
      high glucose condition. A 500 ng/ml of KH902 significantly suppressed high
      glucose-induced migration and sprouting of HRECs through downregulating the
      expression of PI3K and inhibiting the activation of Src, Akt1 and Erk1/2.
      CONCLUSION: Our study indicates that KH902 suppresses high glucose-induced
      migration and sprouting of HRECs through not only binding VEGF, but also PlGF to
      inhibit the activation of Src-Akt1-Erk1/2 pathway. KH902 is a drug that
      potentially inhibits angiogenic pathways involving in DR or other ocular
      neovascular diseases.

PMID- 22958405
TI  - Mechanisms of dyspnea in healthy subjects.
AB  - Dyspnea is a general term used to characterize a range of different descriptors;
      it varies in intensity, and is influenced by a wide variety of factors such as
      cultural expectations and the patient's experiences. Healthy subjects can
      experience dyspnea in different situations, e.g. at high altitude, after breath
      holding, during stressful situations that cause anxiety or panic, and more
      commonly during strenuous exercise. Discussing the mechanisms of dyspnea we need
      to briefly take into account the physiological mechanisms underlying the
      sensation of dyspnea: the functional status of the respiratory muscles, the role
      of chemoreceptors and mechanoreceptors, and how the sense of respiratory motor
      output reaches a level of conscious awareness. We also need to take into account
      theories on the pathophysiological mechanisms of the sensation of dyspnea and the
      possibility that each pathophysiological mechanism produces a distinct quality of
      breathing discomfort. The terms used by subjects to identify different
      characteristics of breathing discomfort - dyspnea descriptors - may contribute to
      understanding the mechanisms of dyspnea and providing the rationale for a
      specific diagnosis.

PMID- 22958406
TI  - The impact of sleep apnoea syndrome on nocturia according to age in men.
AB  - Study Type--Symptom prevalence (cohort) Level of Evidence 2b. What's known on the
      subject? and What does the study add? Sleep apnoea syndrome (SAS) can be a risk
      factor for nocturia, although whether the relationship between nocturia and SAS
      changes according to age remains to be addressed. SAS has a modest impact on
      nocturia frequency and the prevalence of pathological nocturia in young adults
      and middle-aged men. However, SAS may not be a risk factor for nocturia in the
      elderly, and age-related urinary diseases and voiding dysfunctions could over
      ride the influence of SAS on nocturia in the elderly. OBJECTIVE: * To assess the
      association between nocturia and sleep apnoea syndrome (SAS) according to age, as
      well as to determine the factors related to nocturia. PATIENTS AND METHODS: * A
      total of 1757 men who had been referred to a sleep laboratory underwent
      polysomnography. * Nocturia frequency was assessed using a questionnaire, and
      pathological nocturia was defined as the need to void two or more times per
      night. * The Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory
      (BDI) were applied to all study subjects. RESULTS: * Nocturia frequency was
      significantly correlated with age (r = 0.405, P < 0.001) and the apnoea-hypopnoea
      index (AHI) (r = 0.065, P < 0.01). * In those men aged <65 years, significant
      correlations were found between nocturic frequency and age, AHI, BDI and PSQI. *
      Multiple regression analysis showed that age (beta = 0.303, P < 0.001), AHI (beta
      = 0.107 P < 0.001) and benign prostatic hypertrophy (BPH; beta = 0.069, P < 0.01)
      were associated with nocturia, and that the presence of pathological nocturia was
      predicted by BPH (odds ratio [OR], 2.77; P < 0.01), age (OR, 1.09; P < 0.001) and
      AHI (OR, 1.02; P < 0.001). * However, in men aged >65 years, nocturia frequency
      was significantly associated with BDI and PSQI, although no relationship was
      found between nocturia frequency and SAS parameters. * BPH was more frequently
      observed in elderly men with pathological nocturia than in those without
      pathological nocturia (OR, 2.18; P < 0.05). CONCLUSIONS: * In the elderly, SAS
      may not be a risk factor for nocturia. * Age-related urinary diseases and voiding
      dysfunction may over-ride the influence of SAS.

PMID- 22958407
TI  - Systemic inflammation in COPD in relation to smoking status.
AB  - BACKGROUND AND AIMS: Smoking is the main risk factor for the development of
      chronic obstructive pulmonary disease (COPD) that has been recently defined as a
      systemic pulmonary inflammatory disease. However, the impact of smoking itself on
      systemic inflammation in COPD patients has not yet been well established. The aim
      of our study was to investigate the association between inflammatory markers and
      smoking status. MATERIALS AND METHODS: We compared 202 current smokers, 61 ex
      smokers and 57 never-smokers, all COPD patients. Assessments included medical
      history, spirometry, alpha-1 antitrypsin (AAT) genotyping, serum AAT, C-reactive
      protein (CRP), tumor necrosis factor (TNF)-alpha, and soluble tumor necrosis
      factor receptor (sTNFR)-1 and sTNFR-2 concentrations. RESULTS: AAT and CRP
      concentrations in smokers (1.75 +/- 0.51 g/L and 14.4 [9.5-20.5] mg/L) and ex
      smokers (1.69 +/- 0.43 g/L and 12.3 [8.7-16.3] mg/L) were higher than in never
      smokers (1.49 +/- 0.38 g/L and 5.1 [2.5-8.7] mg/L; p < 0.05). sTNFR-1 level was
      higher in smokers than ex-smokers or never-smokers (241.2 pg/mL [145.3-349.4] vs.
      213.7 pg/mL [147.1-280.3] and 205.2 pg/mL [125-275]; p < 0.05). CONCLUSIONS: Our
      data confirm that smoking is associated with increased levels of AAT, CRP, and
      sTNFR-1 in COPD patients, an array of systemic inflammation markers that continue
      to be active even after smoking cessation.

PMID- 22958408
TI  - USA300 Methicillin-resistant Staphylococcus aureus in Cuba.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus is an increasing problem
      in the Caribbean. We investigated the molecular epidemiology of MRSA isolates on
      Cuba. FINDINGS: The predominant clone was of the spa type t149, followed by
      community-associated MRSA USA300. CONCLUSIONS: We report the first molecular
      typing results of MRSA isolates from Cuba.

PMID- 22958409
TI  - 'It's the sense of responsibility that keeps you going': stories and experiences
      of participation from rural community health workers in Guatemala.
AB  - BACKGROUND: In 1978, the Alma-Ata declaration on primary health care (PHC)
      recognized that the world's health issues required more than just hospital-based
      and physician-centered policies. The declaration called for a paradigm change
      that would allow governments to provide essential care to their population in a
      universally acceptable manner. The figure of the community health worker (CHW)
      remains a central feature of participation within the PHC approach, and being a
      CHW is still considered to be an important way of participation within the health
      system. METHODS: This study explores how the values and personal motivation of
      community health workers influences their experience with this primary health
      care strategy in in the municipality of Palencia, Guatemala. To do this, we used
      an ethnographic approach and collected data in January-March of 2009 and 2010 by
      using participant observation and in-depth interviews. RESULTS: We found that the
      CHWs in the municipality had a close working relationship with the mobile health
      team and with the community, and that their positions allowed them to develop
      leadership and teamwork skills that may prove useful in other community
      participation processes. The CHWs are motivated in their work and volunteerism is
      a key value in Palencia, but there is a lack of infrastructure and growth
      opportunities. CONCLUSION: Attention should be paid to keeping the high levels of
      commitment and integration within the health team as well as keeping up
      supervision and economic funds for the program.

PMID- 22958410
TI  - Does urban asthma exist? How climatic changes and urban air pollution intervene
      on asthma and respiratory allergy.

PMID- 22958411
TI  - Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of
      human acetylcholinesterase and butyrylcholinesterase.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurologically degenerative disorder
      that affects more than 20 million people worldwide. The selective
      butyrylcholinesterase (BChE) inhibitors and bivalent cholinesterase (ChE)
      inhibitors represent new treatments for AD. FINDINGS: A series of lycorine
      derivatives (1-10) were synthesized and evaluated for anti-cholinesterase
      activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O
      (methylthio)methyllycorine (7) was a dual inhibitor of human acetylcholinesterase
      (hAChE) and butyrylcholinesterase (hBChE) with IC50 values of 11.40 +/- 0.66 MUM
      and 4.17 +/- 0.29 MUM, respectively. The structure-activity relationships
      indicated that (i) the 1-O-(methylthio)methyl substituent in lycorine was better
      than the 1-O-acetyl group for the inhibition of cholinesterase; (ii) the acylated
      or etherified derivatives of lycorine and lycorin-2-one were more potent against
      hBChE than hAChE; and (iii) the oxidation of lycorine at C-2 decreases the
      activity. CONCLUSION: Acylated or etherified derivatives of lycorine are
      potential dual inhibitors of hBChE and hAChE. Hence, further study on the
      modification of lycorine for ChE inhibition is necessary.

PMID- 22958413
TI  - Words, words, words.

PMID- 22958412
TI  - Montelukast versus inhaled corticosteroids in the management of pediatric mild
      persistent asthma.
AB  - International guidelines recommend the use of inhaled corticosteroids (ICSs) as
      the preferred therapy, with leukotriene receptor antagonists (LTRAs) as an
      alternative, for the management of persistent asthma in children. Montelukast
      (MLK) is the first LTRA approved by the Food and Drug Administration for the use
      in young asthmatic children.Therefore, we performed an analysis of studies that
      compared the efficacy of MLK versus ICSs. We considered eligible for the
      inclusion randomized, controlled trials on pediatric populations with Jadad score
      > 3, with at least 4 weeks of treatment with MLK compared with ICS.Although it is
      important to recognize that ICSs use is currently the recommended first-line
      treatment for asthmatic children, MLK can have consistent benefits in controlling
      asthmatic symptoms and may be an alternative in children unable to use ICSs or
      suffering from poor growth. On the contrary, low pulmonary function and/or high
      allergic inflammatory markers require the corticosteroid use.

PMID- 22958414
TI  - Identification of circulating miRNA biomarkers based on global quantitative real
      time PCR profiling.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs (18-25 nucleotides) that regulate
      gene expression at the post-transcriptional level. Recent studies have
      demonstrated the presence of miRNAs in the blood circulation. Deregulation of
      miRNAs in serum or plasma has been associated with many diseases including
      cancers and cardiovascular diseases, suggesting the possible use of miRNAs as
      diagnostic biomarkers. However, the detection of the small amount of miRNAs found
      in serum or plasma requires a method with high sensitivity and accuracy.
      Therefore, the current study describes polymerase chain reaction (PCR)-based
      methods for measuring circulating miRNAs. Briefly, the procedure involves four
      major steps: (1) sample collection and preparation; (2) global miRNAs profiling
      using quantitative real-time PCR (qRT-PCR); (3) data normalization and analysis;
      and (4) selection and validation of miRNA biomarkers. In conclusion, qRT-PCR is a
      promising method for profiling of circulating miRNAs as biomarkers.

PMID- 22958415
TI  - Life table evaluation of survival and reproduction of the aphid, Sitobion avenae,
      exposed to cadmium.
AB  - The effects of cadmium (Cd) on the development, fecundity, and reproduction of
      the grain aphid, Sitobion avenae Fabricius (Hemiptera: Aphididae) were estimated
      by constructing a life table of S. avenae exposed to Cd. The concentrations of Cd
      in the soil were as follows: 0, 10, 20, 40, 80, and 160 mg/kg. The correlation
      analysis of the Cd concentration in soil and wheat revealed that the amount in
      the wheat increased with the increase of Cd concentrations in soil. The results
      indicated that, the latter part of the reproduction period was significantly
      affected by Cd, according to the curve of the total survival rate (l(x)). The net
      reproductive rate (R(0)), innate capacity of increase (r), and finite rate of
      increase (lambda) of S. avenae all decreased under the stress of Cd, and were
      lowest at a Cd concentration of 20 mg/kg. Cd also negatively affected fecundity
      and m(x) (the number of offspring produced by an individual female). At 20 mg/kg,
      the decline of them was most obvious. In conclusion, survival and reproduction of
      S. avenae were inhibited under the treatment of the heavy metal Cd. Sitobion
      avenae was more sensitive to Cd at concentration of 20 mg/kg compared to the
      other concentrations. This concentration can be used to examine the mechanisms
      behind population genetics and biological mutation of S. avenae when exposed to
      heavy metal.

PMID- 22958416
TI  - Discovery of novel 1,2,4-triazol-5-ones as tumor necrosis factor-alpha inhibitors
      for the treatment of neuropathic pain.
AB  - In this work, synthetic integration of substituted semicarbazides and various
      aliphatic, aryl and heteroaryl acids into 1,2,4-triazol-5-ones was accomplished.
      Following the assessment of neurotoxicity and peripheral analgesic activity, the
      compounds were evaluated in two peripheral models of neuropathic pain, the
      chronic constriction injury and partial sciatic nerve ligation to assess their
      antihyperalgesic and antiallodynic potential. ED(50) studies undertaken for
      selected compounds exhibiting promising efficacies (1c, 3c and 4a) revealed
      values ranging from 13.21 to 39.85 mg/kg in four behavioral assays of
      hyperalgesia and allodynia (spontaneous pain, tactile allodynia, cold allodynia,
      and mechanical hyperalgesia). Mechanistic studies revealed that the compounds
      suppressed the inflammatory component of the neuropathic pain inhibiting tumor
      necrosis factor-alpha and preventing oxidative and nitrosative stress.

PMID- 22958418
TI  - The need to further understand who gets hospitalized for a COPD exacerbation.

PMID- 22958417
TI  - Birth spacing and child mortality: an analysis of prospective data from the
      Nairobi urban health and demographic surveillance system.
AB  - The majority of studies of the birth spacing-child survival relationship rely on
      retrospective data, which are vulnerable to errors that might bias results. The
      relationship is re-assessed using prospective data on 13,502 children born in two
      Nairobi slums between 2003 and 2009. Nearly 48% were first births. Among the
      remainder, short preceding intervals are common: 20% of second and higher order
      births were delivered within 24 months of an elder sibling, including 9% with a
      very short preceding interval of less than 18 months. After adjustment for
      potential confounders, the length of the preceding birth interval is a major
      determinant of infant and early childhood mortality. In infancy, a preceding
      birth interval of less than 18 months is associated with a two-fold increase in
      mortality risks (compared with lengthened intervals of 36 months or longer),
      while an interval of 18-23 months is associated with an increase of 18%. During
      the early childhood period, children born within 18 months of an elder sibling
      are more than twice as likely to die as those born after an interval of 36 months
      or more. Only 592 children experienced the birth of a younger sibling within 20
      months; their second-year mortality was about twice as high as that of other
      children. These results support the findings based on retrospective data.

PMID- 22958419
TI  - Spatial organization of the chicken beta-globin gene domain in erythroid cells of
      embryonic and adult lineages.
AB  - BACKGROUND: The beta-globin gene domains of vertebrate animals constitute
      popular models for studying the regulation of eukaryotic gene transcription. It
      has previously been shown that in the mouse the developmental switching of globin
      gene expression correlates with the reconfiguration of an active chromatin hub
      (ACH), a complex of promoters of transcribed genes with distant regulatory
      elements. Although it is likely that observations made in the mouse beta-globin
      gene domain are also relevant for this locus in other species, the validity of
      this supposition still lacks direct experimental evidence. Here, we have studied
      the spatial organization of the chicken beta-globin gene domain. This domain is
      of particular interest because it represents the perfect example of the so-called
      'strong' tissue-specific gene domain flanked by insulators, which delimit the
      area of preferential sensitivity to DNase I in erythroid cells. RESULTS: Using
      chromosome conformation capture (3C), we have compared the spatial configuration
      of the beta-globin gene domain in chicken red blood cells (RBCs) expressing
      embryonic (3-day-old RBCs) and adult (9-day-old RBCs) beta-globin genes. In
      contrast to observations made in the mouse model, we found that in the chicken,
      the early embryonic beta-globin gene, Epsilon, did not interact with the locus
      control region in RBCs of embryonic lineage (3-day RBCs), where this gene is
      actively transcribed. In contrast to the mouse model, a strong interaction of the
      promoter of another embryonic beta-globin gene, rho, with the promoter of the
      adult beta-globin gene, betaA, was observed in RBCs from both 3-day and 9-day
      chicken embryos. Finally, we have demonstrated that insulators flanking the
      chicken beta-globin gene domain from the upstream and from the downstream
      interact with each other, which places the area characterized by lineage-specific
      sensitivity to DNase I in a separate chromatin loop. CONCLUSIONS: Taken together,
      our results strongly support the ACH model but show that within a domain of
      tissue-specific genes, the active status of a promoter does not necessarily
      correlate with the recruitment of this promoter to the ACH.

PMID- 22958420
TI  - "...Keep mobile, I think that's half the battle." A qualitative study of
      prevention of knee pain in symptomless older adults.
AB  - BACKGROUND: The emphasis on prevention in English health policy continues to
      centre predominantly on major diseases such as coronary heart disease and
      diabetes. A number of key documents detailing self-management techniques and
      prevention of osteoarthritis (OA) are currently available, including the NICE
      guidelines and the Arthritis Foundation's National Public Health Agenda for
      Osteoarthritis. However, few investigations have explored preventative knowledge
      of knee OA amongst the population. In particular, asymptomatic members of the
      population may use further information in considering how to prevent knee pain.
      This study considers perceptions around the prevention of knee pain amongst an
      asymptomatic population; this target population may provide alternative insights
      by which to stimulate preventative behaviours. METHODS: A sample of thirteen
      patients with no current knee pain was selected from responders to a population
      survey. Each interview was tape recorded and fully transcribed. Qualitative
      computer software package NVivo8 was used to manage the data. Thematic analysis
      was conducted using the constant comparative method. RESULTS: The definition and
      causes of knee pain were interpreted in a multitude of ways. The importance of
      prevention was recognised by a sub-set, while a small proportion of participants
      negated the role of prevention. A range of social factors, including early
      adoption of actions, influenced the implementation and continuation of
      preventative behaviours. Individual responsibility for prevention was a key
      theme, although the role of society was also considered. Exercise was cited as a
      principal preventative strategy, although some participants viewed exercise as a
      destructive activity. A number of participants deemed pharmacotherapy to be
      harmful and at odds with normal physiology, instead preferring to adopt
      preventative behaviour over medication usage. CONCLUSIONS: This asymptomatic
      population exhibit considerable breadth and variation in knowledge of
      preventative strategies for knee pain. Similarities in perceptions of prevention
      exist when comparing to the symptomatic population. These range from emphasis on
      individual responsibility, through to observations on the role of exercise and
      pharmacotherapy in knee pain. In general individuals are agreeable to act upon
      recommended treatments in line with NICE guidance. This receptiveness demands a
      greater consideration of preventative strategies in consultations, as well as
      wider availability and promotion of preventative strategies in order to improve
      the musculoskeletal health of the general population.

PMID- 22958421
TI  - Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal
      agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm.
AB  - BACKGROUND: Biofilm production is an important mechanism for bacterial survival
      and its association with antimicrobial resistance represents a challenge for the
      patient treatment. In this study we evaluated the in vitro action of macrolides
      in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas
      aeruginosa recovered from cystic fibrosis (CF) patients. RESULTS: A total of 64
      isolates were analysed. The biofilm inhibitory concentration (BIC) results were
      consistently higher than those obtained by the conventional method, minimal
      inhibitory concentration, (MIC) for most anti-pseudomonal agents tested
      (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P < 0.001, meropenem: P
      = 0.005). When macrolides were associated with the anti-pseudomonal agents, the
      BIC values were reduced significantly for ceftazidime (P < 0.001) and tobramycin
      (P < 0.001), regardless the concentration of macrolides. Strong inhibitory
      quotient was observed when azithromycin at 8 mg/L was associated with all anti
      pseudomonal agents tested in biofilm conditions. CONCLUSIONS: P. aeruginosa from
      CF patients within biofilms are highly resistant to antibiotics but macrolides
      proved to augment the in vitro activity of anti-pseudomonal agents.

PMID- 22958422
TI  - The effect of the ratio of standardized ileal digestible lysine to metabolizable
      energy on growth performance, blood metabolites and hormones of lactating sows.
AB  - A total of 335 lactating sows (Landrace * Large White) were used in two
      experiments to determine the optimum ratio of standardized ileal digestible
      lysine (SID-Lys) to metabolizable energy (ME) for mixed parity sows during
      lactation. In Exp. 1, 185 sows (weighing an average of 256.2 +/- 6.5 kg and
      having an average parity of 3.4 +/- 0.3) were allocated to one of six
      experimental diets in a completely randomized block design within parity groups
      (1, 2, and 3+). The experimental diets were formulated to contain 3.06, 3.16,
      3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows
      throughout a 28 day lactation. All diets provided a similar SID-lysine level
      (0.86%). As a result, the diets provided a SID-Lys:ME ratio of 2.81, 2.72, 2.69,
      2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly (P < 0.01)
      affected by the energy content of the diet as well as by sow parity. Using
      regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21
      and 3.21 Mcal/kg of ME for parity 1, 2, 3+ sows and the entire cohort of sows
      respectively (quadratic; P < 0.01). In addition, the result of feed intake can be
      expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys:ME
      ratio. Litter weight gain was affected by dietary treatment for parity 3+ sows
      and the entire cohort (P < 0.01). Based on regression analysis, litter weight
      gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3+ (quadratic; P <
      0.01) and the entire cohort (quadratic; P < 0.01). Similarly, the result of
      litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID-Lys:ME
      ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows
      (weighing 254.6 +/- 7.3 kg and having an average parity of 3.4 +/- 0.4) were
      allocated to one of five treatments in a completely randomized block design
      within parity (1, 2, and 3+). The experimental diets were formulated to contain
      2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys:ME ratio with all diets providing
      3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation.
      Sow body weight loss was affected by dietary treatment (parity 3+ sows, P = 0.02;
      entire cohort, P < 0.01) and by sow parity (P < 0.01). Litter weight at weaning
      and litter weight gain were affected by dietary treatment for parity 1, 2, 3+
      sows and the entire cohort (P < 0.01) as well as by sow parity (P < 0.01). Plasma
      urea nitrogen (P < 0.01), creatinine (P < 0.01) and non-esterifide fatty acids (P
      = 0.04) were decreased as the SID-Lys:ME ratio of the diet increased. Insulin
      like growth factor-1 (P = 0.02), estradiol (P < 0.01) and luteinizing hormone (P
      = 0.02) were increased as the SID-Lys:ME ratio in diet increased. Based on a
      broken-line model, the estimated SID-Lys:ME ratio to maximize litter weight gain
      was estimated to be 3.05 g/Mcal.

PMID- 22958423
TI  - The lung at high altitude.

PMID- 22958424
TI  - Analyzing the gene expression profile of pediatric acute myeloid leukemia with
      real-time PCR arrays.
AB  - BACKGROUND: The Real-time PCR Array System is the ideal tool for analyzing the
      expression of a focused panel of genes. In this study, we will analyze the gene
      expression profile of pediatric acute myeloid leukemia with real-time PCR arrays.
      METHODS: Real-time PCR array was designed and tested firstly. Then gene
      expression profile of 11 pediatric AML and 10 normal controls was analyzed with
      real-time PCR arrays. We analyzed the expression data with MEV (Multi Experiment
      View) cluster software. Datasets representing genes with altered expression
      profile derived from cluster analyses were imported into the Ingenuity Pathway
      Analysis Tool. RESULTS: We designed and tested 88 real-time PCR primer pairs for
      a quantitative gene expression analysis of key genes involved in pediatric AML.
      The gene expression profile of pediatric AML is significantly different from
      normal control; there are 19 genes up-regulated and 25 genes down-regulated in
      pediatric AML. To investigate possible biological interactions of differently
      regulated genes, datasets representing genes with altered expression profile were
      imported into the Ingenuity Pathway Analysis Tool. The results revealed 12
      significant networks. Of these networks, Cellular Development, Cellular Growth
      and Proliferation, Tumor Morphology was the highest rated network with 36 focus
      molecules and the significance score of 41. The IPA analysis also groups the
      differentially expressed genes into biological mechanisms that are related to
      hematological disease, cell death, cell growth and hematological system
      development. In the top canonical pathways, p53 and Huntington's disease
      signaling came out to be the top two most significant pathways with a p value of
      1.5E-8 and2.95E-7, respectively. CONCLUSIONS: The present study demonstrates the
      gene expression profile of pediatric AML is significantly different from normal
      control; there are 19 genes up-regulated and 25 genes down-regulated in pediatric
      AML. We found some genes dyes-regulated in pediatric AML for the first time as
      FASLG, HDAC4, HDAC7 and some HOX family genes. IPA analysis showed the top
      important pathways for pediatric AML are p53 and Huntington's disease signaling.
      This work may provide new clues of molecular mechanism in pediatric AML.

PMID- 22958425
TI  - Mortality and Clostridium difficile infection: a review.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a common cause of diarrhoea
      in hospitalised patients. Around the world, the incidence and severity of CDI
      appears to be increasing, particularly in the northern hemisphere. The purpose of
      this integrative review was to investigate and describe mortality in hospitalised
      patients with CDI. METHODS: A search of the literature between 1 January 2005 and
      30 April 2011 focusing on mortality and CDI in hospitalised patients was
      conducted using electronic databases. Papers were reviewed and analysed
      individually and themes were combined using integrative methods. RESULTS: All
      cause mortality at 30 days varied from 9% to 38%. Three studies report
      attributable mortality at 30 days, varying from 5.7% to 6.9%. In hospital
      mortality ranged from 8% to 37.2% CONCLUSION: All cause 30 day mortality appeared
      to be high, with 15 studies indicating a mortality of 15% or greater. Findings
      support the notion that CDI is a serious infection and measures to prevent and
      control CDI are needed. Future studies investigating the mortality of CDI in
      settings outside of Europe and North America are needed. Similarly, future
      studies should include data on patient co-morbidities.

PMID- 22958426
TI  - Efficacy and tolerability of taspoglutide versus pioglitazone in subjects with
      type 2 diabetes uncontrolled with sulphonylurea or sulphonylurea-metformin
      therapy: a randomized, double-blind study (T-emerge 6).
AB  - AIMS: This study compared the efficacy and tolerability of taspoglutide versus
      pioglitazone in subjects with type 2 diabetes inadequately controlled with
      sulphonylurea +/- metformin. METHODS: In this double-blind, double-dummy,
      parallel-group trial, 760 subjects (49% male, age 56.4 years, diabetes duration
      8.8 years, body mass index 32.7 kg/m(2) and haemoglobin A1c [HbA1c] 8.3%) were
      randomized (1 : 1 : 1) to subcutaneous injections of taspoglutide 10 or 20 mg
      once weekly or oral pioglitazone 45 mg daily. The primary endpoint was change in
      HbA1c after 24 weeks. RESULTS: Mean (+/-s.e.) HbA1c reductions with taspoglutide
      10 (-1.18 +/- 0.08%) and 20 mg (-1.36 +/- 0.08%) were non-inferior to
      pioglitazone (-1.30 +/- 0.08%) (p = 0.21 and 0.37, respectively); mean treatment
      differences were 0.12 (95% confidence interval: -0.03, -0.26) and -0.06 (-0.20,
      0.08) for taspoglutide 10 and 20 mg versus pioglitazone. Mean (+/-s.e.) changes
      in body weight (kg) were -0.8 +/- 0.3, -1.0 +/- 0.3 and 3.6 +/- 0.3 for
      taspoglutide 10 and 20 mg and pioglitazone, respectively; 8, 11 and 1% of
      patients achieved >=5% weight loss. A higher incidence of adverse events (AEs)
      occurred with taspoglutide, predominantly gastrointestinal disturbances and
      injection-site reactions, resulting in higher rates of discontinuation versus
      pioglitazone. No treatment differences in serious AEs were observed. CONCLUSIONS:
      Taspoglutide offered good glycaemic control similar to pioglitazone, while
      achieving beneficial weight loss rather than weight gain, but was associated with
      more AEs. Due to the higher than expected discontinuation rates, mainly because
      of gastrointestinal intolerability, the taspoglutide clinical programme was
      stopped.

PMID- 22958427
TI  - Human biomonitoring on heavy metals in Ath: methodological aspects.
AB  - The municipality of Ath is characterised by the presence, in its center, of two
      non-ferrous metal industries whose emissions make local residents concerned for
      their health. Therefore, authorities of the Walloon Region and the municipality
      of Ath undertook biomonitoring to assess the impact of those industrial emissions
      on heavy metal body burden in humans.This paper describes the study design and
      methodology used to carry out this human biomonitoring.A random sampling was done
      in the general population, in two areas of Ath: an area centered around the
      industries and a peripheral area. The target population was children (2.5-11
      years) and adults (40-60 years) without occupational exposure. The three-stage
      sampling procedure consisted of a mixture of both mail and telephone recruitment.
      Firstly, 3259 eligible people, identified from a population register, were mailed
      an introductory letter. In a second stage, eligible individuals were contacted by
      phone to propose them to participate in the study. They were randomly contacted
      until the required sample size was obtained. In the third stage, a second mail
      was sent to those who agreed to participate with a questionnaire to be filled
      out. Finally, biological samples (blood and urine) from 278 persons were
      collected. The final participation rate of this study was 24%.This sampling
      procedure, especially designed for the purpose of this biomonitoring study in
      Ath, allowed us to recruit a sample representative of the population of children
      and adults of Ath, reaching the expected sample size in a short period of time.

PMID- 22958428
TI  - Developmental exposure to Passiflora incarnata induces behavioural alterations in
      the male progeny.
AB  - Passiflora incarnata is marketed in many countries as a phytomedicine and is
      prescribed mainly as a sedative and anxiolytic. Even though the directions of
      most marketed phytomedicines recommend them to be used under medical supervision,
      reproductive and developmental studies are sparse and not mandatory for
      regulatory purposes. To evaluate the reproductive and developmental toxicity of
      P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this
      herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata
      treatment did not influence dams' bodyweight or food intake or their reproductive
      performance (post-implantation loss, litter size, litter weight). There was also
      no influence on the physical development of pups (bodyweight gain, day of vaginal
      opening or preputial separation) or their behaviour in the open-field at PND 22,
      35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg
      kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually
      competent. This behavioural disruption was not accompanied by alterations in
      plasma testosterone levels, reproductive-related organs and glands weights or
      sperm count. It is hypothesised that aromatase inhibition may be involved in the
      observed effect.

PMID- 22958429
TI  - Ultrasound guided fine-needle aspiration biopsy of metastases in nonpalpable
      supraclavicular lymph nodes in lung cancer patients.
AB  - BACKGROUND AND OBJECTIVES: To assess frequency and significance of enlarged
      nonpalpable supraclavicular lymph nodes with routine ultrasound (US) evaluation
      and US-guided fineneedle aspiration biopsy (FNAB) for the diagnosis and staging
      of patients with lung cancer. MATERIALS AND METHODS: 106 consecutive patients
      with lung cancer and nonpalpable supraclavicular lymph nodes were evaluated with
      cervical US for the presence of pathological lymph nodes. FNAB was performed in
      patients with nodes with short-axis > 5 mm, rounded shape and missing echogenic
      hilum. RESULTS: 27 (25.5%) patients had enlarged supraclavicular lymph nodes on
      US. Fourteen patients (13.2%) had cytologically proven lymph node involvement.
      Supraclavicular lymph node metastasis was more frequent in patients with
      mediastinal invasion (p = 0.0001) and patients with enlarged lymph nodes on upper
      paratracheal stations on thorax CT (p = 0.0001). No relation was found between
      supraclavicular lymph node involvement and T stage (p = 0.27), distant metastasis
      (p = 0.50) or histological type (p = 0.80). Three patients were upstaged from
      IIIA to IIIB status. US-guided FNAB was the only diagnostic method in 2 patients.
      CONCLUSION: US-guided FNAB is a simple and safe procedure which can document N3
      stage of disease in lung cancer patients. Thereby more invasive and expensive
      diagnostic procedures can be avoided in selected lung cancer patients.

PMID- 22958430
TI  - Crisscross heart with tricuspid atresia diagnosed in utero.
AB  - Crisscross heart is a rare congenital cardiac anomaly in which systemic and
      pulmonary venous streams cross without mixing at atrioventricular level. We
      report a case of crisscross heart with tricuspid atresia, double outlet right
      ventricle, and pulmonary stenosis, which was diagnosed prenatally. 

PMID- 22958431
TI  - Measures of dyspnea in pulmonary rehabilitation.
AB  - Dyspnea is the main symptom perceived by patients affected by chronic
      respiratory diseases. It derives from a complex interaction of signals arising in
      the central nervous system, which is connected through afferent pathway receptors
      to the peripheral respiratory system (airways, lung, and thorax). Notwithstanding
      the mechanism that generates the stimulus is always the same, the sensation of
      dyspnea is often described with different verbal descriptors: these descriptors,
      or linguistic 'clusters', are clearly influenced by socio-individual factors
      related to the patient. These factors can play an important role in identifying
      the etiopathogenesis of the underlying cardiopulmonary disease causing dyspnea.
      The main goal of rehabilitation is to improve dyspnea; hence, quantifying dyspnea
      through specific tools (scales) is essential in order to describe the level of
      chronic disability and to assess eventual changes after intervention.
      Improvements, even if modest, are likely to determine clinically relevant changes
      (minimal clinically important difference, MCID) in patients.Currently there exist
      a large number of scales to classify and characterize dyspnea: the most
      frequently used in everyday clinical practice are the clinical scales (e.g. MRC
      or BDI/TDI, in which information is obtained directly from the patients through
      interview) and psychophysical scales (such as the Borg scale or VAS, which assess
      symptom intensity in response to a specific stimulus, e.g. exercise).It is also
      possible to assess the individual's dyspnea in relation to specific situations,
      e.g. chronic dyspnea (with scales that classify patients according to different
      levels of respiratory disability); exertional dyspnea (with tools that can
      measure the level of dyspnea in response to a physical stimulus); and
      transitional (or 'follow up') dyspnea (with scales that measure the effect in
      time of a treatment intervention, such as rehabilitation).

PMID- 22958432
TI  - A cross-sectional study of the development of volitional control of spatial
      attention in children with chromosome 22q11.2 deletion syndrome.
AB  - BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a 1.5-
      to 3-megabase deletion on the long arm of chromosome 22 and occurs in
      approximately 1 in 4000 live births. Previous studies indicate that children with
      22q11.2DS are impaired on tasks involving spatial attention. However, the degree
      to which these impairments are due to volitionally generated (endogenous) or
      reflexive (exogenous) orienting of attention is unclear. Additionally, the
      efficacy of these component attention processes throughout child development in
      22q11.2DS has yet to be examined. METHODS: Here we compared the performance of a
      wide age range (7 to 14 years) of children with 22q11.2DS to typically developing
      (TD) children on a comprehensive visual cueing paradigm to dissociate the
      contributions of endogenous and exogenous attentional impairments. Paired and two
      sample t-tests were used to compare outcome measures within a group or between
      groups. Additionally, repeated measures regression models were fit to the data in
      order to examine effects of age on performance. RESULTS: We found that children
      with 22q11.2DS were impaired on a cueing task with an endogenous cue, but not on
      the same task with an exogenous cue. Additionally, it was younger children
      exclusively who were impaired on endogenous cueing when compared to age-matched
      TD children. Older children with 22q11.2DS performed comparably to age-matched TD
      peers on the endogenous cueing task. CONCLUSIONS: These results suggest that
      endogenous but not exogenous orienting of attention is selectively impaired in
      children with 22q11.2DS. Additionally, the age effect on cueing in children with
      22q11.2DS suggests a possible altered developmental trajectory of endogenous
      cueing.

PMID- 22958433
TI  - Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and
      Artemisia absinthium L. ethanolic extracts.
AB  - BACKGROUND: Arnica montana L. and Artemisia absinthium L. (Asteraceae) are
      medicinal plants native to temperate regions of Europe, including Romania,
      traditionally used for treatment of skin wounds, bruises and contusions. In the
      present study, A. montana and A. absinthium ethanolic extracts were evaluated for
      their chemical composition, antioxidant activity and protective effect against
      H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. RESULTS:
      A. absinthium extract showed a higher antioxidant capacity than A. montana
      extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance
      capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in
      correlation with its flavonoids and phenolic acids content. Both plant extracts
      had significant effects on the growth of NCTC cells in the range of 10-100 mg/L
      A. montana and 10-500 mg/L A. absinthium. They also protected fibroblast cells
      against hydrogen peroxide-induced oxidative damage, at the same doses. The best
      protection was observed in cell pre-treatment with 10 mg/L A. montana and 10-300
      mg/L A. absinthium, respectively, as determined by Neutral red and lactate
      dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at
      these concentrations, prevented morphological changes induced by hydrogen
      peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and
      A. absinthium extracts restored the proportion of cells in each phase of the cell
      cycle. CONCLUSIONS: A. montana and A. absinthium extracts, rich in flavonoids and
      phenolic acids, showed a good antioxidant activity and cytoprotective effect
      against oxidative damage in fibroblast-like cells. These results provide
      scientific support for the traditional use of A. montana and A. absinthium in
      treatment of skin disorders.

PMID- 22958434
TI  - Pluripotency of induced pluripotent stem cells.
AB  - Recent studies have demonstrated that differentiated somatic cells from various
      mammalian species can be reprogrammed into induced pluripotent stem (iPS) cells
      by the ectopic expression of four transcription factors that are highly expressed
      in embryonic stem (ES) cells. The generation of patient-specific iPS cells
      directly from somatic cells without using oocytes or embryos holds great promise
      for curing numerous diseases that are currently unresponsive to traditional
      clinical approaches. However, some recent studies have argued that various iPS
      cell lines may still retain certain epigenetic memories that are inherited from
      the somatic cells. Such observations have raised concerns regarding the safety
      and efficacy of using iPS cell derivatives for clinical applications. Recently,
      our study demonstrated full pluripotency of mouse iPS cells by tetraploid
      complementation, indicating that it is possible to obtain fully reprogrammed iPS
      cells directly from differentiated somatic cells. Therefore, we propose in this
      review that further comprehensive studies of both mouse and human iPS cells are
      required so that additional information will be available for evaluating the
      quality of human iPS cells.

PMID- 22958435
TI  - Propylthiouracil-induced lupus-like or vasculitis syndrome.
AB  - A 27 year old female with Graves' disease presented with fever, exertional
      dyspnea and polyarthralgia. Erythema nodosum had occured three months earlier.
      The patient declared irregular use of propylthiouracil (PTU) for the last 8
      months. Neutropenia and microscopic hematuria developed in the second week of
      admission. Chest X-ray showed inhomogenous pulmonary opacities, left pleural
      effusion and cardiomegaly. Computed tomography (CT) revealed multiple subpleural
      nodules, left pleural effusion, pericardial effusion, enlarged mediastinal and
      axillary lymph nodes. Bronchoalveolar lavage (BAL) cytology demonstrated
      hemosiderin laden macrophages. Histopathologic examination of the transbronchial
      biopsy specimen revealed a nonspecific inflammation. Serum was positive for ANA,
      P-ANCA, MPO-ANCA, PR3-ANCA and negative for anti-ds-DNA, C-ANCA, C3, C4 and anti
      histone antibody. All symptoms resolved in two months after PTU withdrawal and
      starting steroid treatment. The same clinical manifestations recurred when the
      patient used PTU erronously one month after discharge.This is a case of PTU
      induced-autoimmune disease in whom the accurate distinction between drug-induced
      lupus (DIL) and vasculitis was not possible due to the significant overlap of
      clinical and laboratory findings causing a significant diagnostic challenge for
      the chest physician.

PMID- 22958436
TI  - The overlap phenotype: the (missing) link between asthma and COPD.

PMID- 22958437
TI  - Spontaneous pneumothorax and ozone levels: is there a relation?
AB  - STUDY OBJECTIVES: Although links between meteorological conditions and
      spontaneous pneumothorax (SP) have been proposed, the reports are controversial.
      In this study ozone levels, which are known to have some adverse effects on lung
      tissues, were investigated as a potential triggering factor of SP. At present
      there is not sufficient information about the effects of ozone on SP. METHODS: Of
      a total 79 pneumothorax patients recruited for the study, 21 secondary
      pneumothorax cases were excluded. In the remaining 58 SP patients, meteorological
      data at the time of SP occurrence were recorded. RESULTS: The number of SP
      patients was higher in spring than in the other seasons (p < 0.05). There was an
      association between the SP frequency and the average ozone level at different
      seasons (F 3,52 = 19.45, p = 0.001). The average ozone level was higher in spring
      (363 +/- 25 Dobson) than during the other seasons (autumn 296 +/- 18 Dobson;
      summer 321 +/- 26 Dobson; winter 324 +/- 32 Dobson) (p = 0.001). There was a
      positive correlation between SP frequency and the average ozone values for each
      season (r = 0.301, p = 0.024). There was no significant correlation between the
      severity of SP and ozone level (r = 0.236, p = 0.16). CONCLUSIONS: The number of
      SP patients increases in spring when ozone levels are highest. Ozone is known to
      affect alveolar cells and cause interstitial edema. Ozone causes damage to the
      lung interstitium by way of oxidative stress. Rupture of unrecognized underlying
      blebs/bullae has been proposed as a cause of SP. Increased levels of ozone may be
      a triggering factor for these ruptures.

PMID- 22958438
TI  - Neuroinflammation and oxidative stress in rostral ventrolateral medulla
      contribute to neurogenic hypertension induced by systemic inflammation.
AB  - BACKGROUND: In addition to systemic inflammation, neuroinflammation in the brain,
      which enhances sympathetic drive, plays a significant role in cardiovascular
      diseases, including hypertension. Oxidative stress in rostral ventrolateral
      medulla (RVLM) that augments sympathetic outflow to blood vessels is involved in
      neural mechanism of hypertension. We investigated whether neuroinflammation and
      oxidative stress in RVLM contribute to hypertension following chronic systemic
      inflammation. METHODS: In normotensive Sprague-Dawley rats, systemic inflammation
      was induced by infusion of Escherichia coli lipopolysaccharide (LPS) into the
      peritoneal cavity via an osmotic minipump. Systemic arterial pressure and heart
      rate were measured under conscious conditions by the non-invasive tail-cuff
      method. The level of the inflammatory markers in plasma or RVLM was analyzed by
      ELISA. Protein expression was evaluated by Western blot or immunohistochemistry.
      Tissue level of superoxide anion (O(2)(-)) in RVLM was determined using the
      oxidation-sensitive fluorescent probe dihydroethidium. Pharmacological agents
      were delivered either via infusion into the cisterna magna with an osmotic
      minipump or microinjection bilaterally into RVLM. RESULTS: Intraperitoneal
      infusion of LPS (1.2 mg/kg/day) for 14 days promoted sustained hypertension and
      induced a significant increase in plasma level of C-reactive protein, tumor
      necrosis factor-alpha (TNF-alpha), or interleukin-1beta (IL-1beta). This LPS
      induced systemic inflammation was accompanied by activation of microglia,
      augmentation of IL-1beta, IL-6, or TNF-alpha protein expression, and O(2)(-)
      production in RVLM, all of which were blunted by intracisternal infusion of a
      cycloxygenase-2 (COX-2) inhibitor, NS398; an inhibitor of microglial activation,
      minocycline; or a cytokine synthesis inhibitor, pentoxifylline. Neuroinflammation
      in RVLM was also associated with a COX-2-dependent downregulation of endothelial
      nitric oxide synthase and an upregulation of intercellular adhesion molecule-1.
      Finally, the LPS-promoted long-term pressor response and the reduction in
      expression of voltage-gated potassium channel, Kv4.3 in RVLM were antagonized by
      minocycline, NS398, pentoxifylline, or a superoxide dismutase mimetic, tempol,
      either infused into cisterna magna or microinjected bilaterally into RVLM. The
      same treatments, on the other hand, were ineffective against LPS-induced systemic
      inflammation. CONCLUSION: These results suggest that systemic inflammation
      activates microglia in RVLM to induce COX-2-dependent neuroinflammation that
      leads to an increase in O(2)(-) production. The resultant oxidative stress in
      RVLM in turn mediates neurogenic hypertension.

PMID- 22958439
TI  - ABO blood group is a predictor of survival in patients undergoing surgery for
      renal cell carcinoma.
AB  - What's known on the subject? and What does the study add? Some evidence suggests
      that ABO blood type may be a risk factor for cancer incidence and prognosis. For
      example, a large study recently discovered an increased incidence of pancreatic
      cancer in patients with non-O blood type; however, it is not known whether blood
      group correlates with outcomes in patients with RCC. We found a significant and
      independent association between ABO blood group and overall survival in patients
      undergoing surgery for locoregional RCC. Specifically, we identified non-O blood
      type as a predictor of mortality. OBJECTIVE: * To determine whether ABO blood
      group is associated with survival after nephrectomy or partial nephrectomy for
      renal cell carcinoma (RCC). PATIENTS AND METHODS: * We conducted a retrospective
      cohort study of 900 patients who underwent surgery for locoregional RCC between
      1997 and 2008 at a single institution. * Covariates included age, gender, race,
      American Society of Anesthesiology Physical Status, preoperative anaemia and
      hypoalbuminemia, tumour characteristics, lymph node status, procedure performed,
      transfusion status and ABO blood group. * Primary outcomes were overall (OS) and
      disease-specific survival (DSS). * Univariable survival analyses were performed
      using the Kaplan-Meier and log-rank methods. Multivariable analysis was performed
      using a Cox proportional hazards model. RESULTS: * The 3-year OS estimate was 75%
      (95%CI 70-79%) for O blood group and 68% (95% CI 63-73%) for non-O blood group
      (P= 0.072). The 3-year DSS was 81% (95% CI 76-85%) for O blood group and 76%
      (95%CI 71-80%) for non-O blood group (P= 0.053). * In the multivariable analysis
      for OS, non-O blood type was significantly associated with decreased OS (HR 1.68,
      95%CI 1.18-2.39; P= 0.004) but not DSS (HR 1.53, 95%CI 0.97-2.41; P= 0.065).
      CONCLUSION: * These data suggest that ABO blood group is independently associated
      with OS in patients undergoing surgery for locoregional RCC. ABO blood group has
      not been previously recognized as a predictor of survival in RCC.

PMID- 22958440
TI  - Vancomycin-resistant vanB-type Enterococcus faecium isolates expressing varying
      levels of vancomycin resistance and being highly prevalent among neonatal
      patients in a single ICU.
AB  - BACKGROUND: Vancomycin-resistant isolates of E. faecalis and E. faecium are of
      special concern and patients at risk of acquiring a VRE colonization/infection
      include also intensively-cared neonates. We describe here an ongoing high
      prevalence of VanB type E. faecium in a neonatal ICU hardly to identify by
      routine diagnostics. METHODS: During a 10 months' key period 71 E. faecium
      isolates including 67 vanB-type isolates from 61 patients were collected non
      selectively. Vancomycin resistance was determined by different MIC methods (broth
      microdilution, Vitek(r) 2) including two Etest(r) protocols (McFarland 0.5/2.0.
      on Mueller-Hinton/Brain Heart Infusion agars). Performance of three chromogenic
      VRE agars to identify the vanB type outbreak VRE was evaluated (BrillianceTM VRE
      agar, chromIDTM VRE agar, CHROMagarTM VRE). Isolates were genotyped by SmaI- and
      CeuI-macrorestriction analysis in PFGE, plasmid profiling, vanB Southern
      hybridisations as well as MLST typing. RESULTS: Majority of vanB isolates (n =
      56, 79%) belonged to a single ST192 outbreak strain type showing an identical
      PFGE pattern and analyzed representative isolates revealed a chromosomal
      localization of a vanB2-Tn5382 cluster type. Vancomycin MICs in cation-adjusted
      MH broth revealed a susceptible value of <=4 mg/L for 31 (55%) of the 56 outbreak
      VRE isolates. Etest(r) vancomycin on MH and BHI agars revealed only two vanB VRE
      isolates with a susceptible result; in general Etest(r) MIC results were about 1
      to 2 doubling dilutions higher than MICs assessed in broth and values after the
      48 h readout were 0.5 to 1 doubling dilutions higher for vanB VRE. Of all vanB
      type VRE only three, three and two isolates did not grow on BrillianceTM VRE
      agar, chromIDTM VRE agar and CHROMagarTM VRE, respectively. Permanent cross
      contamination via the patients' surrounding appeared as a possible risk factor
      for permanent VRE colonization/infection. CONCLUSIONS: Low level expression of
      vanB resistance may complicate a proper routine diagnostics of vanB VRE and mask
      an ongoing high VRE prevalence. A high inoculum and growth on rich solid media
      showed the highest sensitivity in identifying vanB type resistance.

PMID- 22958441
TI  - A quasi-experimental evaluation of an interpersonal communication intervention to
      increase insecticide-treated net use among children in Zambia.
AB  - BACKGROUND: This paper presents results from an evaluation of the effect of a
      community health worker (CHW) -based, interpersonal communication campaign (IPC)
      for increasing insecticide-treated mosquito net (ITN) use among children in
      Luangwa District, Zambia, an area with near universal coverage of ITNs and
      moderate to low malaria parasite prevalence. METHODS: A quasi-experimental
      community randomized control trial was conducted from 2008 to 2010. CHWs were the
      unit of randomization. Cross-sectional data were collected from houses in both
      2008 and 2010 using simple random sampling of a complete household enumeration of
      the district. A difference-in -differences approach was used to analyse the data.
      RESULTS: ITN use among children <5 years old in households with >=1 ITN increased
      overall from 54% in 2008 to 81% in 2010 (chi(2) = 96.3, p <0.01); however, there
      was no difference in increase between the treatment and control arms in 2010 (p
      >0.05). ITN use also increased among children five to 14 years old from 37% in
      2008 to 68% in 2010. There was no indication that the CHW-based intervention
      activities had a significant effect on increasing ITN use in this context, over
      and above what is already being done to disseminate information on the importance
      of using an ITN to prevent malaria infection. DISCUSSION: ITN use increased
      dramatically in the district between 2008 and 2010. It is likely that IPC
      activities in general may have contributed to the observed increase in ITN use,
      as the increased observed in this study was far higher than the increase observed
      between 2008 and 2010 malaria indicator survey (MIS) estimates. Contamination
      across control communities, coupled with linear settlement patterns and
      subsequent behavioural norms related to communication in the area, likely
      contributed to the observed increase in net use and null effect in this study.

PMID- 22958442
TI  - Managing a traumatic ventricular septal defect with atrial septal defect occluder
      device.
AB  - Traumatic ventricular septal defects are rare complications of blunt and
      penetrating chest trauma. Patients are usually referred because of shock or
      cardiac tamponade. Focusing on the critical condition of the patient leads to
      missing the presence of traumatic ventricular septal defects. In this case
      report, we introduce a patient with a large traumatic ventricular septal defect,
      which was diagnosed 40 days after a penetrating cardiac trauma and was finally
      treated with transcatheter closure.

PMID- 22958444
TI  - Qualitative aspects of exertional dyspnea in patients with restrictive lung
      disease.
AB  - Restrictive lung disease is a broad term encompassing a number of conditions in
      which lung volumes are reduced. Dyspnea is a common clinical manifestation of
      restrictive lung disease and frequently becomes a prominent and disabling symptom
      that undermines patients' ability to function and engage in activities of daily
      living (especially in those with more advanced restriction). Effective management
      of this disabling symptom awaits a better understanding of its underlying
      physiology. In recent decades, our understanding of the mechanisms of dyspnea in
      restrictive lung disease has been improved by a small, but significant, body of
      research. One approach to the study of dyspnea is to identify the major
      qualitative dimensions of the symptom in an attempt to uncover different
      underlying neurophysiologic mechanisms. This article will review the existing
      literature on the intensity and qualitative dimensions of dyspnea during exercise
      in patients with restrictive lung disease. The main focus will be on interstitial
      lung disease (ILD), since it is the prototypical restrictive disease.

PMID- 22958443
TI  - Explaining the increase in coronary heart disease mortality in Syria between 1996
      and 2006.
AB  - BACKGROUND: Despite advances made in treating coronary heart disease (CHD),
      mortality due to CHD in Syria has been increasing for the past two decades. This
      study aims to assess CHD mortality trends in Syria between 1996 and 2006 and to
      investigate the main factors associated with them. METHODS: The IMPACT model was
      used to analyze CHD mortality trends in Syria based on numbers of CHD patients,
      utilization of specific treatments, trends in major cardiovascular risk factors
      in apparently healthy persons and CHD patients. Data sources for the IMPACT model
      included official statistics, published and unpublished surveys, data from
      neighboring countries, expert opinions, and randomized trials and meta-analyses.
      RESULTS: Between 1996 and 2006, CHD mortality rate in Syria increased by 64%,
      which translates into 6370 excess CHD deaths in 2006 as compared to the number
      expected had the 1996 baseline rate held constant. Using the IMPACT model, it was
      estimated that increases in cardiovascular risk factors could explain
      approximately 5140 (81%) of the CHD deaths, while some 2145 deaths were prevented
      or postponed by medical and surgical treatments for CHD. CONCLUSION: Most of the
      recent increase in CHD mortality in Syria is attributable to increases in major
      cardiovascular risk factors. Treatments for CHD were able to prevent about a
      quarter of excess CHD deaths, despite suboptimal implementation. These findings
      stress the importance of population-based primary prevention strategies targeting
      major risk factors for CHD, as well as policies aimed at improving access and
      adherence to modern treatments of CHD.

PMID- 22958445
TI  - Journal of Neurodevelopmental Disorders is now a fully open access journal.

PMID- 22958446
TI  - Real-time assessment of cigarette smoke particle deposition in vitro.
AB  - BACKGROUND: Recently there has been a rapid increase in approaches to assess the
      effects of cigarette smoke in vitro. Despite a range of gravimetric and chemical
      methods, there is a requirement to identify simpler and more reliable methods to
      quantify in vitro whole smoke dose, to support extrapolation and comparisons to
      human/in vivo dose. We have previously characterised an in vitro exposure system
      using a Borgwaldt RM20S smoking machine and a chamber exposing cellular cultures
      to whole smoke at the air-liquid interface. In this study we demonstrate the
      utility of a quartz crystal microbalance (QCM), using this exposure system, to
      assess real-time cigarette smoke particulate deposition during a 30 minute smoke
      exposure. Smoke was generated at various dilutions (1:5-1:400, smoke:air) using
      two cigarette products, 3R4F Kentucky reference and 1 mg commercially available
      cigarettes. The QCM, integrated into the chamber, assessed particulate deposition
      and data generated were compared to traditional chemical spectrofluorometric
      analysis. RESULTS: The QCM chamber was able to detect mass differences between
      the different products within the nanogram range. 3R4F reference cigarette smoke
      deposition ranged from 25.75 +/-2.30 MUg/cm2 (1:5) to 0.22 +/-0.03 MUg/cm2
      (1:400). 1 mg cigarette smoke deposition was less and ranged from 1.42 +/-0.26
      MUg/cm2 (1:5), to 0.13 +/-0.02 MUg/cm2 (1:100). Spectrofluorometric analysis
      demonstrated statistically significant correlation of particulate deposition with
      the QCM (p < 0.05), and regression R2 value were 97.4 %. The fitted equation for
      the linear model which describes the relationship is: QCM = -0.6796 + 0.9744
      chemical spectrofluorescence. CONCLUSIONS: We suggest the QCM is a reliable,
      effective and simple tool that can be used to quantify smoke particulate
      deposition in real-time, in vitro and can be used to quantify other aerosols
      delivered to our chamber for assessment.

PMID- 22958447
TI  - High burden of breast cancer in Belgium: recent trends in incidence (1999-2006)
      and historical trends in mortality (1954-2006).
AB  - INTRODUCTION: In Belgium, breast cancer mortality has been monitored since 1954,
      whereas cancer incidence data have only been made available for a few years. In
      this article we update historical trends of breast cancer mortality and describe
      the recent breast cancer incidence. METHODS: Incidence data were extracted from
      the Belgium Cancer Registry from 2004 to 2006 for the Walloon and Brussels
      Regions and Belgium, and from 1999 to 2006 for the Flemish Region. The
      Directorate-general Statistics and Economic information provided the mortality
      data for the years 1954-1999 and 2004. The regional authorities of the Flemish
      and Brussels Regions provided the mortality data for the years 2000-2003 and 2005
      2006. RESULTS: In 2004, the World age-standardised breast cancer incidence for
      the whole of Belgium was 110 per 100, 000 person-years for all ages; and 172, 390
      and 345 per 100, 000 person-years for the 35-49, 50-69, and 70+ age groups,
      respectively. The incidence rate was slightly higher in each age group in the
      Brussels Region. In Flanders, where the incidence could be observed during a
      longer period, an increase was observed until 2003 in the 50-69 age group,
      followed by a decrease. To the contrary, in the oldest age group, incidence
      continued to rise over the whole period, whereas no change in incidence was
      observed between 1999 and 2006 in the 35-49 age group.Mortality increased until
      the late 1980s and afterwards decreased in all regions and in age groups younger
      than 70. In women of 70 years and older, the decline began later. CONCLUSIONS:
      The burden of breast cancer in Belgium is very high. In 2004, Belgium ranked
      first for the age-standardised incidence rate in Europe for all ages combined and
      in the 35-49 and 50-69 age groups. The impact of the known risk factors and of
      mammographic screening should be further studied. The mortality rate in Belgium
      ranked lower than incidence, suggesting favourable survival. Plausible
      explanations for the discrepancy between incidence and mortality are discussed.

PMID- 22958448
TI  - Joint action on monitoring injuries in Europe (JAMIE).
AB  - The hospital sector provides the best setting for collecting information as this
      information relates to the most severe cases (while less severe cases are treated
      by family doctors of school nurses for instance) and information can be obtained
      easily on a large number of cases at low cost (while surveys are expensive and
      suffering serious deficiencies as regards the specificity of data obtained). The
      WHO-International Classification of Diseases and its derivative classification on
      external causes of injuries provide the proper tools for standardised data
      collection on injuries treated within the health sector.In order to make injury
      data collection affordable for countries to collect and to have a greater number
      of countries joining the data exchange efforts, JAMIE envisages to have a
      relatively limited set data elements being collected in a representative sample
      of emergency departments in countries, while collecting in a few departments
      deeper information on the circumstances of the injury event. BACKGROUND: Injuries
      due to accidents or violence constitute a major public health problem globally
      and also within the 27 member states of the European Union (EU-MSs). In spite of
      the magnitude and the severity of the problem, injury surveillance systems are
      not yet sufficiently well developed to accurately quantify the burden of injuries
      on individuals, health services and society in the EU-region. Much of the injury
      information generated up until now is not comparable between countries, and not
      between registers, due to the lack of harmonised methodology and classification.
      PROJECT OBJECTIVES: JAMIE project aims at having by 2015 a common emergency
      departmental-based surveillance system for injury prevention in operation in all
      MS. Such a system should report on external causes of injuries due to accidents
      and violence as part of the Community Statistics on Public Health. The project
      will build on previous work on injury data exchange initiated by the European
      Commission (EC) and a number of EU-member states, which resulted to the so called
      Injury Data Base hosted by the EC.

PMID- 22958449
TI  - Application of imputation methods to genomic selection in Chinese Holstein
      cattle.
AB  - Missing genotypes are a common feature of high density SNP datasets obtained
      using SNP chip technology and this is likely to decrease the accuracy of genomic
      selection. This problem can be circumvented by imputing the missing genotypes
      with estimated genotypes. When implementing imputation, the criteria used for SNP
      data quality control and whether to perform imputation before or after data
      quality control need to consider. In this paper, we compared six strategies of
      imputation and quality control using different imputation methods, different
      quality control criteria and by changing the order of imputation and quality
      control, against a real dataset of milk production traits in Chinese Holstein
      cattle. The results demonstrated that, no matter what imputation method and
      quality control criteria were used, strategies with imputation before quality
      control performed better than strategies with imputation after quality control in
      terms of accuracy of genomic selection. The different imputation methods and
      quality control criteria did not significantly influence the accuracy of genomic
      selection. We concluded that performing imputation before quality control could
      increase the accuracy of genomic selection, especially when the rate of missing
      genotypes is high and the reference population is small.

PMID- 22958450
TI  - Anxiety and depression in COPD patients and correlation with sputum and BAL
      cytology.
AB  - BACKGROUND AND AIMS: Anxiety and depression are common in patients with chronic
      obstructive pulmonary disease (COPD). The degree of lung function may not explain
      anxiety and depression. The aim of our study was to assess the psychological
      aspects of COPD, to test the BODE index (a composite score of body mass,
      obstruction, dyspnea and exercise capacity), and to evaluate the association
      between atypical cytologic findings of sputum, bronchoalveolar lavage (BAL) and
      the pyschological components of the disease. METHODS: COPD was classsified
      according to the GOLD stages based on forced expiratory volume in 1 second (FEV1)
      in 60 stable patients. The BODE index was calculated for grading COPD. The
      Hospital anxiety and depression (HAD) scale was used to appraise the anxiety and
      depression symptoms. Cytologic examination of sputum and BAL samples were
      performed in each patient. The cytologic findings were classified as normal,
      mild, moderate or severe atypia. RESULTS: The overall prevalance of anxiety and
      depression symptoms was 41.7% and 46.7% respectively. The prevalance of these
      symptoms increased with increasing BODE stages and correlated well with the
      severity of atypical BAL cytology results (p < 0.001). Dyspnea and reduced
      exercise capacity were the predominant mechanisms leading to anxiety and
      depression symptoms associated with COPD. CONCLUSIONS: We conclude that the BODE
      index is superior to GOLD stratification for explaining anxiety and depression
      symptoms in COPD. BAL cytologic findings, which reflect the distal parenchymal
      lung structure, correlated significantly with the presence of the anxiety and
      depression symptoms.

PMID- 22958451
TI  - miRNA-dysregulation associated with tenderness variation induced by acute stress
      in Angus cattle.
AB  - miRNAs are a class of small, single-stranded, non-coding RNAs that perform post
      transcriptional repression of target genes by binding to 3' untranslated regions.
      Research has found that miRNAs involved in the regulation of many metabolic
      processes. Here we uncovered that the beef quality of Angus cattle sharply
      diversified after acute stress. By performing miRNA microarray analysis, 13
      miRNAs were significantly differentially expressed in stressed group compared to
      control group. Using a bioinformatics method, 135 protein-coding genes were
      predicted as the targets of significant differentially expressed miRNAs. Gene
      Ontology (GO) term and Ingenuity Pathway Analysis (IPA) mined that these target
      genes involved in some important pathways, which may have impact on meat quality
      and beef tenderness.

PMID- 22958452
TI  - Atrial arrhythmia, triggering events and conduction abnormalities in isolated
      murine RyR2-P2328S hearts.
AB  - AIM: RyR2 mutations are associated with catecholaminergic polymorphic
      tachycardia, a condition characterized by ventricular and atrial arrhythmias. The
      present experiments investigate the atrial electrophysiology of homozygotic
      murine RyR2-P2328S (RyR2(S/S)) hearts for ectopic triggering events and for
      conduction abnormalities that might provide a re-entrant substrate. METHODS:
      Electrocardiograph recordings were made from regularly stimulated RyR2(S/S) and
      wild type (WT) hearts, perfused using a novel modified Langendorff preparation.
      This permitted the simultaneous use of either floating intracellular
      microelectrodes to measure action potential (AP) parameters, or a multielectrode
      array to measure epicardial conduction velocity (CV). RESULTS: RyR2(S/S) showed
      frequent sustained tachyarrhythmias, delayed afterdepolarizations and ectopic
      APs, increased interatrial conduction delays, reduced epicardial CVs and reduced
      maximum rates of AP depolarization ((dV/dt)(max)), despite similar effective
      refractory periods, AP durations and AP amplitudes. Effective interatrial CVs and
      (dV/dt)(max) values of APs following ectopic (S2) stimulation were lower than
      those of APs following regular stimulation and decreased with shortening S1S2
      intervals. However, although RyR2(S/S) atria showed arrhythmias over a wider
      range of S1S2 intervals, the interatrial CV and (dV/dt)(max) of S2 APs provoking
      such arrhythmias were similar in RyR2(S/S) and WT. CONCLUSIONS: These results
      suggest that abnormal intracellular Ca(2+) homoeostasis produces both arrhythmic
      triggers and a slow-conducting arrhythmic substrate in RyR2(S/S) atria. A similar
      mechanism might also contribute to arrhythmogenesis in other conditions,
      associated with diastolic Ca(2+) release, such as atrial fibrillation.

PMID- 22958453
TI  - Identification and functional analysis of gene cluster involvement in
      biosynthesis of the cyclic lipopeptide antibiotic pelgipeptin produced by
      Paenibacillus elgii.
AB  - BACKGROUND: Pelgipeptin, a potent antibacterial and antifungal agent, is a non
      ribosomally synthesised lipopeptide antibiotic. This compound consists of a beta
      hydroxy fatty acid and nine amino acids. To date, there is no information about
      its biosynthetic pathway. RESULTS: A potential pelgipeptin synthetase gene
      cluster (plp) was identified from Paenibacillus elgii B69 through genome
      analysis. The gene cluster spans 40.8 kb with eight open reading frames. Among
      the genes in this cluster, three large genes, plpD, plpE, and plpF, were shown to
      encode non-ribosomal peptide synthetases (NRPSs), with one, seven, and one
      module(s), respectively. Bioinformatic analysis of the substrate specificity of
      all nine adenylation domains indicated that the sequence of the NRPS modules is
      well collinear with the order of amino acids in pelgipeptin. Additional
      biochemical analysis of four recombinant adenylation domains (PlpD A1, PlpE A1,
      PlpE A3, and PlpF A1) provided further evidence that the plp gene cluster
      involved in pelgipeptin biosynthesis. CONCLUSIONS: In this study, a gene cluster
      (plp) responsible for the biosynthesis of pelgipeptin was identified from the
      genome sequence of Paenibacillus elgii B69. The identification of the plp gene
      cluster provides an opportunity to develop novel lipopeptide antibiotics by
      genetic engineering.

PMID- 22958454
TI  - Impaired multiple object tracking in children with chromosome 22q11.2 deletion
      syndrome.
AB  - BACKGROUND: Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) occurs in
      approximately 1:4,000 live births with a complex and variable presentation that
      includes medical, socioemotional and psychological symptoms with intellectual
      impairment. Cognitive impairments in spatiotemporal and visuospatial attention
      have also been reported. However, maintenance of selective attention to dynamic
      and interacting objects has not been systematically investigated in children with
      22q11.2DS. METHODS: We used a multiple object tracking task to assay capacity and
      resolution performance of children with 22q11.2DS aged 7 to 14 years versus age
      matched typically developing (TD) peers. RESULTS: Children with 22q11.2DS but not
      TD children demonstrated impaired performance when task demands increased due to
      an increase in the number of targets presented, but not from an increase in
      object speed. Task performance in children with 22q11.2DS was also unrelated to
      intelligence or measures of attention deficit hyperactivity disorder.
      CONCLUSIONS: These findings suggest that children with 22q11.2DS may be
      particularly susceptible to dynamic crowding of objects with increasing cognitive
      demands related to monitoring multiple targets reflecting a reduced acuity in
      spatiotemporal cognitive representation.

PMID- 22958455
TI  - Steroidogenesis in sheep pregnancy with intrauterine growth retardation by high
      altitude hypoxia: effects of maternal altitudinal status and antioxidant
      treatment.
AB  - Sheep pregnancy in high-altitude environments frequently involves hypoxia and
      oxidative stress and causes intrauterine growth retardation. The adverse effects
      of altitude on fetal growth can be prevented by the administration of antioxidant
      vitamins, but the mechanisms responsible are not well known. The maintenance of a
      viable pregnancy depends largely on adequate placental steroidogenesis,
      especially in the last two-thirds of pregnancy. Thus, in the present study we
      evaluated the effect of antioxidant vitamins (C and E) on plasma concentrations
      of progesterone and 17beta-oestradiol during the last two-thirds of high-altitude
      pregnancies in ewes both native and naive to the high-altitude environment. In
      addition, pregnancy outcomes were evaluated by determining the bodyweight of
      newborn lambs. Sex steroid patterns differed between ewes with and without
      vitamin supplementation. Concentrations of plasma progesterone and 17beta
      oestradiol were significantly higher in the supplemented groups from
      approximately 40 days before parturition until near term. Newborn weights were
      significantly lower in animals not adapted to the higher altitude, and vitamin
      supplementation prevented this decrease. In conclusion, the administration of
      antioxidant vitamins in the present study enhanced placental steroidogenesis,
      thus favouring fetal development in pregnancies developing at high altitudes.

PMID- 22958456
TI  - A systematic review and meta-analysis of randomized and non-randomized studies
      comparing laparoscopic and open abdominoperineal resection for rectal cancer.
AB  - AIM: Evidence supporting the role of laparoscopy in abdominoperineal resection
      (APR) is limited. This study compared the short-term and long-term outcomes and
      complications associated with open and laparoscopic APR. METHOD: The Medline,
      Cochrane and Embase databases were searched for publications comparing open and
      laparoscopic APR. The rates of local and distant recurrence of rectal cancer were
      compared as the primary end-point. The occurrence of complications related to the
      two procedures was studied as the secondary end-point. The adequacy of cancer
      resection and postoperative recovery were also compared in a secondary analysis.
      Combined and separate analyses were performed for randomized and non-randomized
      studies. RESULTS: Eight publications comparing open and laparoscopic APR were
      identified. The rates of local and distant disease recurrence were lower after
      laparoscopic surgery compared with open APR (odds ratio 2.736 and 1.994, 95%
      confidence interval 1.137-6.584 and 1.062-3.742, P = 0.025 and P = 0.032,
      respectively). Early postoperative complications were fewer after laparoscopic
      APR (OR 2.159, 95% CI 1.426-3.269, P = 0.000). No significant benefit of either
      technique was observed in the secondary analysis. CONCLUSION: The long-term
      oncological benefits of laparoscopic APR are not convincingly superior to open
      surgery and need further validation. The laparoscopic approach is apparently
      associated with fewer postoperative complications, yet its role in improving the
      short-term outcomes is uncertain.

PMID- 22958457
TI  - Use of machine-learning classifiers to predict requests for preoperative acute
      pain service consultation.
AB  - OBJECTIVE:   The purpose of this project was to determine whether machine
      learning classifiers could predict which patients would require a preoperative
      acute pain service (APS) consultation. DESIGN:   Retrospective cohort. SETTING:  
      University teaching hospital. SUBJECTS:   The records of 9,860 surgical patients
      posted between January 1 and June 30, 2010 were reviewed. OUTCOME MEASURES:  
      Request for APS consultation. A cohort of machine-learning classifiers was
      compared according to its ability or inability to classify surgical cases as
      requiring a request for a preoperative APS consultation. Classifiers were then
      optimized utilizing ensemble techniques. Computational efficiency was measured
      with the central processing unit processing times required for model training.
      Classifiers were tested using the full feature set, as well as the reduced
      feature set that was optimized using a merit-based dimensional reduction
      strategy. RESULTS:   Machine-learning classifiers correctly predicted
      preoperative requests for APS consultations in 92.3% (95% confidence intervals
      [CI], 91.8-92.8) of all surgical cases. Bayesian methods yielded the highest area
      under the receiver operating curve (0.87, 95% CI 0.84-0.89) and lowest training
      times (0.0018 seconds, 95% CI, 0.0017-0.0019 for the NaiveBayesUpdateable
      algorithm). An ensemble of high-performing machine-learning classifiers did not
      yield a higher area under the receiver operating curve than its component
      classifiers. Dimensional reduction decreased the computational requirements for
      multiple classifiers, but did not adversely affect classification performance.
      CONCLUSIONS:   Using historical data, machine-learning classifiers can predict
      which surgical cases should prompt a preoperative request for an APS
      consultation. Dimensional reduction improved computational efficiency and
      preserved predictive performance.

PMID- 22958458
TI  - Blood transfusion, embolisation and nephrectomy after percutaneous
      nephrolithotomy (PCNL).
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Percutaneous treatment
      for renal stone disease is associated with a risk of significant morbidity. Our
      large UK series provides contemporary data on the risk of vascular complications
      and admission to the Intensive Care Unit (ICU) after PCNL. When compared with
      recent international databases, these data support the current evidence that
      better outcomes can be achieved in centres performing large numbers of
      procedures. These data add to the debate for the centralisation of specialist
      stone surgery. OBJECTIVE: To audit the outcome of percutaneous nephrolithotomy
      (PCNL) at a UK stone centre over a 10-year period, and provide patients with
      understandable contemporary data on blood loss and vascular risk. PATIENTS AND
      METHODS: A single centre retrospective analysis of all PCNLs undertaken between
      April 2000 and December 2010. The association between transfusion and patient
      age, operative duration and positive preoperative mid-stream urine (MSU) sample
      was subject to statistical analysis. RESULTS: Data on 568 patients was analysed.
      21 were paediatric cases with a mean (range) age of 8 (2-16) years; 547 were
      adult cases with a mean (range) age of 55 (17-84) years. 3.8% of adult patients
      (21/547) received a blood transfusion; mean age 60 years (55 years in those not
      transfused) with a mean operative duration of 119 min (103 min in those not
      transfused). 23.8% of patients transfused had a confirmed preoperative urinary
      tract infection compared with 16.1% of those not transfused. Seven patients
      underwent angiography, with five having selective arterial embolisation (0.9%).
      There were no deaths in this series although one patient (0.2%) required an
      urgent nephrectomy due to cardiovascular instability from bleeding. CONCLUSIONS:
      Large UK series that provides contemporary data for consent on vascular risk at
      PCNL. The risk of transfusion is associated with increased patient age, operative
      duration and the presence of a positive preoperative MSU sample. Data compares
      favourably with other large published series, and supports the argument for
      centralisation of percutaneous stone management.

PMID- 22958459
TI  - Effects of breathing maneuver and sitting posture on muscle activity in
      inspiratory accessory muscles in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: To determine the influence of breathing maneuver and sitting posture
      on tidal volume (TV), respiratory rate (RR), and muscle activity of the
      inspiratory accessory muscles in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: Twelve men with COPD participated in the study.
      Inductive respiratory plethysmography and surface electromyography were used to
      simultaneously measure TV, RR, and muscle activity of the inspiratory accessory
      muscles [the scalenus (SM), sternocleidomastoid (SCM), and pectoralis major (PM)
      muscles] during quiet natural breathing (QB) and pursed-lips breathing (PLB) in
      three sitting postures: neutral position (NP), with armm support (WAS), and with
      arm and head support (WAHS). RESULTS: Two-way repeated-measures analysis of
      variance was employed. In a comparison of breathing patterns, PLB significantly
      increased TV and decreased RR compared to QB. Muscle activity in the SM and SCM
      increased significantly in PLB compared to QB. In a comparison of sitting
      postures, the muscle activity of the SM, SCM, and PM increased in the forward
      leaning position. CONCLUSIONS: The results suggest that in COPD, PLB induced a
      favorable breathing pattern (increased TV and reduced RR) compared to QB.
      Additionally, WAS and WAHS positions increased muscle activity of the inspiratory
      accessory muscles during inspiration versus NP. Differential involvement of
      accessory respiratory muscles can be readily studied in COPD patients, allowing
      monitoring of respiratory load during pulmonary rehabilitation.

PMID- 22958460
TI  - Investigation of volatile organic biomarkers derived from Plasmodium falciparum
      in vitro.
AB  - BACKGROUND: There remains a need for techniques that improve the sensitive
      detection of viable Plasmodium falciparum as part of diagnosis and therapeutic
      monitoring in clinical studies and usual-care management of malaria infections. A
      non-invasive breath test based on P. falciparum-associated specific volatile
      organic compounds (VOCs) could fill this gap and provide insights into parasite
      metabolism and pathogenicity. The aim of this study was to determine whether VOCs
      are present in the headspace above in vitro P. falciparum cultures. METHODS: A
      novel, custom-designed apparatus was developed to enable efficient headspace
      sampling of infected and non-infected cultures. Conditions were optimized to
      support cultures of high parasitaemia (>20%) to improve the potential detection
      of parasite-specific VOCs. A number of techniques for VOC analysis were
      investigated including solid phase micro-extraction using two different polarity
      fibres, and purge and trap/thermal desorption, each coupled to gas chromatography
      mass spectrometry. Each experiment and analysis method was performed at least on
      two occasions. VOCs were identified by comparing their mass spectra against
      commercial mass spectral libraries. RESULTS: No unique malarial-specific VOCs
      could be detected relative to those in the control red blood cell cultures. This
      could reflect sequestration of VOCs into cell membranes and/or culture media but
      solvent extractions of supernatants and cell lysates using hexane,
      dichloromethane and ethyl acetate also showed no obvious difference compared to
      control non-parasitized cultures. CONCLUSIONS: Future in vivo studies analysing
      the breath of patients with severe malaria who are harbouring a parasite biomass
      that is significantly greater than achievable in vitro may yet reveal specific
      clinically-useful volatile chemical biomarkers.

PMID- 22958461
TI  - Prospective evaluation of the usefulness of C-reactive protein in the diagnosis
      of neonatal sepsis in a sub-Saharan African region.
AB  - BACKGROUND: Sepsis is one of the most common causes of morbidity and mortality
      in the newborn. Early diagnosis and treatment is vital to improve outcome. The
      present study was therefore carried out to determine the usefulness of C-reactive
      protein (CRP) for evaluation of neonatal sepsis in Port Harcourt, Nigeria in Sub
      Saharan Africa. METHOD: Four hundred and twenty neonates with clinical suspicion
      of sepsis were prospectively studied over a 6 month period. Blood was obtained
      from each subject recruited for the qualitative estimation of CRP. Blood culture
      was used as gold standard for diagnosis of NNS. RESULTS: Of 420 neonates studied,
      196 (46.7%) had positive CRP while 181 (43.1%) had positive blood culture. The
      sensitivity, specificity, positive and negative predictive values of CRP were
      74.0%, 74.1%, 68.4% and 79.0% respectively. CONCLUSION: The qualitative method of
      estimating CRP which is cheap and rapid has moderate sensitivity, specificity and
      negative predictive value.

PMID- 22958462
TI  - Photoacoustic technique: a new method for measuring the rheologic properties of
      human bronchial mucus.

PMID- 22958463
TI  - Childhood and family influences on body mass index in early adulthood: findings
      from the Ontario Child Health Study.
AB  - BACKGROUND: Overweight and obesity are steadily increasing worldwide with the
      greatest prevalence occurring in high-income countries. Many factors influence
      body mass index (BMI); however multiple influences assessed in families and
      individuals are rarely studied together in a prospective design. Our objective
      was to model the impact of multiple influences at the child (low birth weight,
      history of maltreatment, a history of childhood mental and physical conditions,
      and school difficulties) and family level (parental income and education,
      parental mental and physical health, and family functioning) on BMI in early
      adulthood. METHODS: We used data from the Ontario Child Health Study, a
      prospective, population-based study of 3,294 children (ages 4-16 years) enrolled
      in 1983 and followed up in 2001 (N = 1,928; ages 21-35 years). Using multilevel
      models, we tested the association between family and child-level variables and
      adult BMI after controlling for sociodemographic variables and health status in
      early adulthood. RESULTS: At the child level, presence of psychiatric disorder
      and school difficulties were related to higher BMI in early adulthood. At the
      family level, receipt of social assistance was associated with higher BMI,
      whereas family functioning, having immigrant parents and higher levels of
      parental education were associated with lower BMI. We found that gender moderated
      the effect of two risk factors on BMI: receipt of social assistance and presence
      of a medical condition in childhood. In females, but not in males, the presence
      of these risk factors was associated with higher BMI in early adulthood.
      CONCLUSION: Overall, these findings indicate that childhood risk factors
      associated with higher BMI in early adulthood are multi-faceted and long-lasting.
      These findings highlight the need for preventive interventions to be implemented
      at the family level in childhood.

PMID- 22958465
TI  - Changes in blood hemoglobin and blood gases PaO2 and PaCO2 in severe COPD overa
      three-year telemonitored program of long-term oxygen treatment.
AB  - BACKGROUND: Information on the effects of long-term oxygen treatment (LTOT) on
      blood hemoglobin (Hb) in severe COPD are limited. The aim was to assess blood Hb
      values in severe COPD, and investigate the time-course of both Hb and blood gas
      changes during a 3-year telemetric LTOT. METHODS: A cohort of 132 severe COPD
      patients (94 males; 71.4 years +/- 8.8 sd), newly admitted to the tele-LTOT
      program, was investigated. Subjects were divided according to their original
      blood Hb: group A: <13 g/dL; group B: >=13 < 15 g/dL; group C: >= 5 < 16 g/dL;
      group D: >=16 g/dL. Blood Hb (g/dL), PaO2 and PaCO2 (mmHg), SaO2 (%), and BMI
      were measured at LTOT admission (t0), and at least quarterly over three years (t1
      t3). Wilcoxon test was used to compare t0 vs. t1 values; linear regression to
      assess a possible Hb-BMI relationship; ANOVA to compare changes in Hb time
      courses over the 3 years. RESULTS: LTOT induced a systematic increase of PaO2,
      and changes were significant since the first year (from 52.1 mmHg +/- 6.6sd to
      65.1 mmHg +/- 8.7 sd, p < 0.001). Changes in SaO2 were quite similar. Comparable
      and equally significant trends were seen in all subgroups (p < 0.001). PaCO2
      dropped within the first year of LTOT (from 49.4 mmHg +/- 9.1sd to 45.9 mmHg +/
      7.5 sd, p < 0.001): the t0-t1 comparison proved significant (p < 0.01) only in
      subgroups with the highest basal Hb, who showed a further PaCO2 decline over the
      remaining two years (p < 0.001). Hb tended to normalization during LTOT only in
      subgroups with basal Hb > 15 g/dl (ANOVA p < 0.001); anemic subjects (Hb < 13
      g/dl) ameliorated not significantly in the same period (ANOVA = 0.5). Survival
      was independent of the original blood Hb. Anemia and polyglobulia are differently
      prevalent in COPD, the latter being the most represented in our cohort. LTOT
      affected both conditions, but to a different extent and according to different
      time-courses. The most striking Hb improvement was in polyglobulic patients in
      whom also PaO2, PaCO2 and SaO2 dramatically improved. In anemic subjects effects
      were smaller and slower, oxygenation being equally ameliorated by LTOT.
      CONCLUSIONS: LTOT effects on Hb and PaCO2 are regulated by an Hb-dependent
      gradient which seems independent of the original impairment of blood gases and of
      effects on oxygenation.

PMID- 22958464
TI  - Can immunotherapy be useful as a "functional cure" for infection with Human
      Immunodeficiency Virus-1?
AB  - Immunotherapy aims to assist the natural immune system in achieving control over
      viral infection. Various immunotherapy formats have been evaluated in either
      therapy-naive or therapy-experienced HIV-infected patients over the last 20
      years. These formats included non-antigen specific strategies such as cytokines
      that stimulate immunity or suppress the viral replication, as well as antibodies
      that block negative regulatory pathways. A number of HIV-specific therapeutic
      vaccinations have also been proposed, using in vivo injection of inactivated
      virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing
      HIV genes. A specific format of therapeutic vaccines consists of ex vivo loading
      of autologous dendritic cells with one of the above mentioned antigenic formats
      or mRNA encoding HIV antigens.This review provides an extensive overview of the
      background and rationale of these different therapeutic attempts and discusses
      the results of trials in the SIV macaque model and in patients. To date success
      has been limited, which could be explained by insufficient quality or strength of
      the induced immune responses, incomplete coverage of HIV variability and/or
      inappropriate immune activation, with ensuing increased susceptibility of target
      cells.Future attempts at therapeutic vaccination should ideally be performed
      under the protection of highly active antiretroviral drugs in patients with a
      recovered immune system. Risks for immune escape should be limited by a better
      coverage of the HIV variability, using either conserved or mosaic sequences.
      Appropriate molecular adjuvants should be included to enhance the quality and
      strength of the responses, without inducing inappropriate immune activation.
      Finally, to achieve a long-lasting effect on viral control (i.e. a "functional
      cure") it is likely that these immune interventions should be combined with anti
      latency drugs and/or gene therapy.

PMID- 22958466
TI  - Descriptors of dyspnea in obstructive lung diseases.
AB  - In obstructive lung diseases such as asthma and COPD dyspnea is a common
      respiratory symptom with different characteristics given the different pathogenic
      mechanisms: in COPD initially it can occur during exertion but then it increases
      progressively along with the airflow obstruction, whereas in asthma it occurs
      episodically and is caused by transient bronchoconstriction.The language of
      dyspnea includes a large range of clinical descriptors which have been evaluated
      for their correlation (of one or several descriptors) with underlying
      physiologic/physiopathologic mechanisms. These studies were done in asthma rather
      than in COPD, and dyspnea descriptors were found to be useful in identifying
      patients with life-threatening asthma. However further studies are needed to
      further explore such descriptors and their clinical utility.This review discusses
      dyspnea mechanisms in various obstructive lung disease subsets as well as the
      descriptors of dyspnea and their utility in clinical practice.

PMID- 22958467
TI  - Homology modeling and functional annotation of bubaline pregnancy associated
      glycoprotein 2.
AB  - BACKGROUND: Pregnancy associated glycoproteins form a diverse family of
      glycoproteins that are variably expressed at different stages of gestation. They
      are probably involved in immunosuppression of the dam against the feto-maternal
      placentome. The presence of the products of binucleate cells in maternal
      circulation has also been correlated with placentogenesis and placental re
      modeling. The exact structure and function of the gene product is unknown due to
      limitations on obtaining purified pregnancy associated glycoprotein preparations.
      RESULTS: Our study describes an in silico derived 3D model for bubaline pregnancy
      associated glycoprotein 2. Structure-activity features of the protein were
      characterized, and functional studies predict bubaline pregnancy associated
      glycoprotein 2 as an inducible, extra-cellular, non-essential, N-glycosylated,
      aspartic pro-endopeptidase that is involved in down-regulation of complement
      pathway and immunity during pregnancy. The protein is also predicted to be
      involved in nutritional processes, and apoptotic processes underlying fetal
      morphogenesis and re-modeling of feto-maternal tissues. CONCLUSION: The
      structural and functional annotation of buPAG2 shall allow the designing of
      mutants and inhibitors for dissection of the exact physiological role of the
      protein.

PMID- 22958469
TI  - Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a
      prostaglandin mediated mechanism.
AB  - Mastitis or other infectious diseases have been related to reduced fertility in
      cattle. Inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) are
      released in response to infection and may have negative effects on embryo
      development. In the current study the effect of exposure to TNFalpha on the
      development of in vitro fertilized bovine embryos was examined. Indomethacin, a
      prostaglandin synthesis inhibitor, was used to determine if blockade of
      prostaglandin synthesis would alter the effects of TNFalpha. Ovaries were
      obtained from a local abattoir and immature COC were isolated from 2-10 mm
      follicles, in vitro matured and fertilized. After fertilization, groups of
      presumptive zygotes were randomly placed into either control development medium,
      medium containing 25 ng/mL TNFalpha or medium containing 25 ng/mL TNFalpha plus 1
      MUg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7
      of culture. Fewer embryos exposed to TNFalpha alone reached the blastocyst stage
      (17.5 +/- 2.4%, P < 0.01) compared with controls (30.5 +/- 2.4%) or embryos
      developed in TNFalpha plus indomethacin (25.8 +/- 2.8%). There was no difference
      between control embryos and embryos developed in TNFalpha plus indomethacin.
      These results indicate that TNFalpha is inhibitory to the in vitro development of
      bovine embryos and that this inhibition may be mediated by prostaglandins because
      it can be blocked by indomethacin.

PMID- 22958471
TI  - Twenty-year cytogenetic and molecular follow-up of a patient with ring chromosome
      15: a case report.
AB  - INTRODUCTION: Ring chromosome 15 is a rare disorder, with only a few over 40
      cases reported in the literature. There are only two previous reports of cases
      where patients with ring chromosome 15 have been followed-up. CASE PRESENTATION:
      We report here on the 20-year clinical and cytogenetic follow-up of a patient
      with a ring chromosome 15. Our patient, a Caucasoid Asian woman, presented with
      short stature, microcephaly, minor dysmorphic features, hyperextensible knees,
      generalized hirsutism, cafe-au-lait and small hypochromic spots spread over her
      face and the front of her chest and abdomen, dorsolumbar scoliosis and mild
      intellectual disability. She was followed-up from the age of eight to 28 years.
      When she was 27 years old, she was reported by her mother to present with
      compulsive overeating and an aggressive mood when challenged. Karyotyping
      revealed that the majority of her cells harbored one normal chromosome and one
      ring chromosome. Silver staining revealed the presence of the nucleolar organizer
      region in the ring chromosome. Ring loss and/or secondary aberrations exhibited a
      slight increase over time, from 4.67% in 1989 to 7.67% in 2009, with the presence
      of two monocentric rings, cells with interlocked rings, a dicentric ring, and
      broken or open rings. A genome-wide array technique detected a 5.5Mb deletion in
      15q26.2. CONCLUSIONS: We observed that some phenotypic alterations in our patient
      can be associated with gene loss and haploinsufficiency. Other features may be
      related to different factors, including ring instability and epigenetic factors.

PMID- 22958470
TI  - Molecular and phylogenetic analysis of matrix gene of avian influenza viruses
      isolated from wild birds and live bird markets in the USA.
AB  - BACKGROUND: Wild birds are the natural hosts for influenza A viruses (IAVs) and
      provide a niche for the maintenance of this virus. OBJECTIVES: This study was
      undertaken to analyze nucleotide sequences of the matrix (M) gene of AIVs
      isolated from wild birds and live bird markets (LBMs) to index the changes
      occurring in this gene. METHODS: M-gene of 229 avian influenza virus (AIV)
      isolates obtained from wild birds and LBMs was amplified and sequenced. Full
      length sequences (~900 nt.) thus obtained were analyzed to identify changes that
      may be associated with resistance to adamantanes. Phylogenetic analysis of all
      sequences was performed using clustalw, and evolutionary distances were
      calculated by maximum composite likelihood method using mega (ver. 5.0) software.
      RESULTS: Twenty-seven different viral subtypes were represented with H3N8 being
      the most dominant subtype in wild birds and H7N2 being the predominant subtype
      among isolates from LBMs. Phylogenetic analysis of the M-gene showed a high
      degree of nucleotide sequence identity with US isolates of AIVs but not with
      those of Asian or European lineages. While none of the isolates from wild birds
      had any antiviral resistance-associated mutations, 17 LBM isolates carried
      polymorphisms known to cause reduced susceptibility to antiviral drugs
      (adamantanes). Of these 17 isolates, 16 had S31N change and one isolate had V27A
      mutation. CONCLUSIONS: These results indicate independent evolution of M-gene in
      the absence of any antiviral drugs leading to mutations causing resistance
      indicating the need for continued active surveillance of AIVs.

PMID- 22958468
TI  - Social 'wanting' dysfunction in autism: neurobiological underpinnings and
      treatment implications.
AB  - Most behavioral training regimens in autism spectrum disorders (ASD) rely on
      reward-based reinforcement strategies. Although proven to significantly increase
      both cognitive and social outcomes and successfully reduce aberrant behaviors,
      this approach fails to benefit a substantial number of affected individuals.
      Given the enormous amount of clinical and financial resources devoted to
      behavioral interventions, there is a surprisingly large gap in our knowledge of
      the basic reward mechanisms of learning in ASD. Understanding the mechanisms for
      reward responsiveness and reinforcement-based learning is urgently needed to
      better inform modifications that might improve current treatments. The
      fundamental goal of this review is to present a fine-grained literature analysis
      of reward function in ASD with reference to a validated neurobiological model of
      reward: the 'wanting'/'liking' framework. Despite some inconsistencies within the
      available literature, the evaluation across three converging sets of
      neurobiological data (neuroimaging, electrophysiological recordings, and
      neurochemical measures) reveals good evidence for disrupted reward-seeking
      tendencies in ASD, particularly in social contexts. This is most likely caused by
      dysfunction of the dopaminergic-oxytocinergic 'wanting' circuitry, including the
      ventral striatum, amygdala, and ventromedial prefrontal cortex. Such a conclusion
      is consistent with predictions derived from diagnostic criteria concerning the
      core social phenotype of ASD, which emphasize difficulties with spontaneous self
      initiated seeking of social encounters (that is, social motivation). Existing
      studies suggest that social 'wanting' tendencies vary considerably between
      individuals with ASD, and that the degree of social motivation is both malleable
      and predictive of intervention response. Although the topic of reward
      responsiveness in ASD is very new, with much research still needed, the current
      data clearly point towards problems with incentive-based motivation and learning,
      with clear and important implications for treatment. Given the reliance of
      behavioral interventions on reinforcement-based learning principles, we believe
      that a systematic focus on the integrity of the reward system in ASD promises to
      yield many important clues, both to the underlying mechanisms causing ASD and to
      enhancing the efficacy of existing and new interventions.

PMID- 22958472
TI  - CRF01_AE dominates the HIV-1 epidemic in Indonesia.
AB  - BACKGROUND: The HIV epidemic in Indonesia remains concentrated in vulnerable
      populations, namely injecting drug users (IDUs), commercial sex workers (CSWs)
      and men who have sex with men (MSM). We aimed to determine the HIV-1 subtypes
      present in Indonesia and to establish the extent of the viral overlap between
      individuals with different risk factors. METHODS: Venous blood samples were
      collected from HIV-positive individuals primarily from sexually transmissible
      infection clinics and drug rehabilitation centres in Bali and Jakarta, and
      applied to filter paper. A polymerase chain reaction-based assay designed to
      amplify a 330-bp region of the HIV-1 envelope was used to determine HIV-1 subtype
      result and to perform phylogenetic analysis. RESULTS: Of the 175 individuals
      recruited to the study, a subtype result was obtained for 108 (62%). Four
      subtypes were found to exist in the population, CRF01_AE (n=96, 88.9%), B (n=10,
      9.3%), C (n=1, 0.9%) and G (n=1, 0.9%). Of these 108 individuals, 65 (60%) were
      IDUs, and the remaining 40% were CSWs, MSM, transgender individuals, people with
      multiple sexual partners or those with no obvious risk factor. CRF01_AE was found
      to be more common among IDUs with 100% of individuals infected with this subtype.
      Subtype B was more common among MSM and CSWs (P=<0.001). Phylogenetic analysis
      revealed a lack of viral segregation between risk groups. CONCLUSIONS: In
      Indonesia, CRF01_AE continues to dominate the HIV epidemic, although HIV subtype
      B is responsible for a significant number of sexually acquired infections.

PMID- 22958473
TI  - The association between residential area characteristics and mental health
      outcomes among men and women in Belgium.
AB  - AIM: Recently, interest has grown in the association between contextual factors
      and health outcomes. This study questions whether mental health complaints vary
      according to the socio-economic characteristics of the residential area where
      people live. The gender-specific patterns are studied. METHODS: Complaints of
      depression and generalized anxiety were measured by means of the relevant
      subscales of the Symptoms Checklist 90-Revised. Multilevel models were estimated
      with PASW statistics 18, based on a unique dataset, constructed by merging data
      from the Belgian Health Interview Surveys from 2001 and 2004 with data from 264
      municipalities derived from Statistics Belgium and the General Socio-Economic
      Survey. MAIN FINDINGS: The results of this exploratory study indicate that the
      local unemployment rate is associated with complaints of depression among women.
      CONCLUSION: This study suggests that policy should approach the male and female
      population differently when implementing mental health prevention campaigns.

PMID- 22958476
TI  - Efficacy and safety of intravenous immunoglobulin as adjuvant treatment for
      refractory neuropathic pain. Results of an open-label, multicenter study.
AB  - INTRODUCTION:   Neuropathic pain is frequently associated with many peripheral
      nervous system diseases and its successful treatment is an area of significant
      and critical unmet need. METHODS:   Twenty adult outpatients of both sexes who
      had been suffering from painful polyneuropathy resistant to conventional
      therapies for at least 6 months and up to a maximum of 5 years and who reported
      severity of pain >60 units on a visual analog scale (VAS) at baseline were
      included in this open-label pilot study. Patients were randomly 1:1 allocated to
      receive adjuvant intravenous immunoglobulin (IVIG) (Flebogamma(r), 2 g/kg) in
      addition to their regular therapy or to continue with the previous therapy
      (control group). RESULTS:   The mean value of pain intensity (VAS) in the IVIG
      group dropped from 88 at baseline to 49 after the first week, and to 28 after 4
      weeks, while values in the control group only slightly changed, from 85 to 78
      after 1 week and to 75 after 4 weeks (P < 0.01). Almost 100% of patients reported
      strong/medium pain (Short Form McGill Pain Questionnaire) in both groups at
      baseline, while after 4-8 weeks, pain was reduced to moderate/light in 90% of
      patients in the IVIG group, whereas no improvement was reported in the control
      group (P < 0.01). In patients' quality of life, scores of the IVIG group (Short
      Form 36, Clinical Global Impression of Change, and Patient Global Impression of
      Change questionnaires) in all the follow-up were significantly higher than those
      of the control group (P < 0.01). CONCLUSION:   This unblinded pilot study showed
      a beneficial effect of IVIG on neuropathic pain intensity and quality of life in
      patients resistant to conventional treatments.

PMID- 22958475
TI  - Atypical subtrochanteric femoral shaft fractures: role for mechanics and bone
      quality.
AB  - Bisphosphonates are highly effective agents for reducing osteoporotic fractures
      in women and men, decreasing fracture incidence at the hip and spine up to 50%.
      In a small subset of patients, however, these agents have recently been
      associated with 'atypical femoral fractures' (AFFs) in the subtrochanteric region
      or the diaphysis. These fractures have several atypical characteristics,
      including occurrence with minimal trauma; younger age than typical osteoporotic
      fractures; occurrence at cortical, rather than cancellous sites; early
      radiographic appearance similar to that of a stress fracture; transverse fracture
      pattern rather than the familiar spiral or transverse-oblique morphologies;
      initiation on the lateral cortex; and high risk of fracture on the contralateral
      side, at the same location as the initial fracture. Fracture is a mechanical
      phenomenon that occurs when the loads applied to a structure such as a long bone
      exceed its load-bearing capacity, either due to a single catastrophic overload
      (traumatic failure) or as a result of accumulated damage and crack propagation at
      sub-failure loads (fatigue failure). The association of AFFs with no or minimal
      trauma suggests a fatigue-based mechanism that depends on cortical cross
      sectional geometry and tissue material properties. In the case of AFFs,
      bisphosphonate treatment may alter cortical tissue properties, as these agents
      are known to alter bone remodeling. This review discusses the use of
      bisphosphonates, their effects on bone remodeling, mechanics and tissue
      composition, their significance as an effective therapy for osteoporosis, and why
      these agents may increase fracture risk in a small population of patients. 

PMID- 22958474
TI  - Infant siblings and the investigation of autism risk factors.
AB  - Infant sibling studies have been at the vanguard of autism spectrum disorders
      (ASD) research over the past decade, providing important new knowledge about the
      earliest emerging signs of ASD and expanding our understanding of the
      developmental course of this complex disorder. Studies focused on siblings of
      children with ASD also have unrealized potential for contributing to ASD
      etiologic research. Moving targeted time of enrollment back from infancy toward
      conception creates tremendous opportunities for optimally studying risk factors
      and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a
      traditional sibling study, which already incorporates close developmental follow
      up of at-risk infants through the third year of life, is essentially reconfigured
      as an enriched-risk pregnancy cohort study. This review considers the enriched
      risk pregnancy cohort approach of studying infant siblings in the context of
      current thinking on ASD etiologic mechanisms. It then discusses the key features
      of this approach and provides a description of the design and implementation
      strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism
      Risk Longitudinal Investigation (EARLI).

PMID- 22958477
TI  - Enuresis in South African children: prevalence, associated factors and parental
      perception of treatment.
AB  - Study Type--Symptom Prevalence (prospective cohort) Level of Evidence 2a. What's
      known on the subject? and What does the study add? Nocturnal enuresis is a common
      childhood problem. Although its prevalence is known in many countries, no data
      are available from South Africa and it is difficult to extrapolate data from
      developed countries to a population with such diverse conditions and resource
      poor settings. This study is the first to report on the 16% prevalence rate and
      the low level of parental knowledge of enuresis in South African children aged
      between 5 and 10 years. OBJECTIVES: * To establish the prevalence of NE in 5-10
      year old South African children in a cross-sectional study using a parent
      completed questionnaire. * To establish the parental perception and associated
      factors of mono-symptomatic nocturnal enuresis (MNE) treatment and treatment
      success rates in 5-10 year old children from South Africa. PATIENTS AND METHODS:
      * A total of 4700 questionnaires were distributed to children at 37 selected
      schools willing to participate from South Africa. Parents anonymously filled out
      the questionnaire. * Data were reported as frequencies and percentages of NE in
      tables according to different gender and age groups. * The Chi-square test
      compared proportions between groups and Fisher's Exact test corrected for small
      numbers of observations (n <= 5). Age differences were determined using Student's
      t-test. A P-value <= 0.5 was considered to be statistically significant. RESULTS:
      * The questionnaire's response rate was 72.1%, with 3389 children included in the
      study. * The overall prevalence of NE was 16.0%-14.4% of children suffered from
      mono-symptomatic NE (MNE). The prevalence of NE in boys was double that in that
      in girls. * Only 28.3% had received some form of treatment, whereas 13.5% had
      been medically treated by a doctor. Parents' awareness of treatment modalities
      available is outdated and most of the management of MNE was done by parents
      themselves, albeit with low success rates. * A positive family history was found
      in 50.5% of children suffering from MNE. * Constipation was a problem in 15.8% of
      children with enuresis. CONCLUSIONS: * This is the first study to estimate the
      prevalence of NE and report on the parental perception and possible associated
      factors of enuresis in children from South Africa. The study showed that South
      African children have a similar prevalence rate of NE (16%) when compared with
      other countries. * The possible associated factors with MNE in South Africa
      include constipation and a family history of enuresis. * Finally, there are low
      levels of parental knowledge of treatment modalities of MNE, leaving many
      children untreated.

PMID- 22958478
TI  - Clock-controlled mir-142-3p can target its activator, Bmal1.
AB  - BACKGROUND: microRNAs (miRNAs) are shown to be involved in the regulation of
      circadian clock. However, it remains largely unknown whether miRNAs can regulate
      the core clock genes (Clock and Bmal1). RESULTS: In this study, we found that mir
      142-3p directly targeted the 3'UTR of human BMAL1 and mouse Bmal1. The over
      expression (in 293ET and NIH3T3 cells) and knockdown (in U87MG cells) of mir-142
      3p reduced and up-regulated the Bmal1/BMAL1 mRNA and protein levels,
      respectively. Moreover, the expression level of mir-142-3p oscillated in serum
      shocked NIH3T3 cells and the results of ChIP and luciferase reporter assays
      suggested that the expression of mir-142-3p was directly controlled by
      CLOCK/BMAL1 heterodimers in NIH3T3 cells. CONCLUSIONS: Our study demonstrates
      that mir-142-3p can directly target the 3'UTR of Bmal1. In addition, the
      expression of mir-142-3p is controlled by CLOCK/BMAL1 heterodimers, suggesting a
      potential negative feedback loop consisting of the miRNAs and the core clock
      genes. These findings open new perspective for studying the molecular mechanism
      of circadian clock.

PMID- 22958479
TI  - Preoperative neutrophil to lymphocyte ratio >5 is a prognostic factor for
      recurrent colorectal cancer.
AB  - AIM: Previous studies have demonstrated that raised preoperative neutrophil to
      lymphocyte ratio (NLR) is associated with poor prognosis in colorectal cancer
      (CRC). The aim of this study was to assess whether preoperative NLR could predict
      patients at risk of recurrence of CRC. METHOD: All consecutive patients who
      underwent surgical resection for CRC over a 2-year period at our institution were
      analysed. Demographic data including CRC recurrence were prospectively collected
      from our institutional cancer database. CRC recurrence was diagnosed on
      radiological and endoscopic histopathological data. Preoperative NLR was
      calculated on baseline blood results, with a value >5 being a poor prognostic
      factor. Parametric survival analysis was used to identify risk factors for CRC
      recurrence. Hazard ratios (HRs) were calculated for gender, CRC stage using Jass
      score, preoperative NLR and CRC site. P < 0.05 was considered statistically
      significant. RESULTS: In all, 297 patients (157 men) underwent CRC resection at a
      median age of 70 years (range 23-93); 164 patients had colon cancer, 111 rectal
      cancer and 22 recto-sigmoid cancer. The distribution by stage of CRC was 30.2%
      for stage 1, 23.8% for stage 2, 19.5% for stage 3 and 26.5% for stage 4. Over a
      median follow-up period of 3.35 (0.1-8) years, 59 (19.8%) patients had recurrent
      CRC. Multivariate analysis revealed CRC stage (HR 8.69, 95% CI 3.85-19.6, P <
      0.0001) and NLR >5 (HR 1.81, 95% CI 1.07-3.07, P = 0.028) to be significant and
      independent risk factors predictive of recurrent CRC. CONCLUSION: These data
      suggest that preoperative NLR >5 is predictive of CRC recurrence.

PMID- 22958481
TI  - Control of multidrug resistant bacteria in a tertiary care hospital in India.
AB  - BACKGROUND: The objective of this study was to assess the impact of
      antimicrobial stewardship programs on the multidrug resistance patterns of
      bacterial isolates. The study comprised an initial retrospective analysis of
      multidrug resistance in bacterial isolates for one year (July 2007-June 2008)
      followed by prospective evaluation of the impact of Antimicrobial Stewardship
      programs on resistance for two years and nine months (July 2008-March 2011).
      SETTING: A 300-bed tertiary care private hospital in Gurgaon, Haryana (India)
      FINDINGS:  METHODS: Study Design* July 2007 to June 2008: Resistance patterns of
      bacterial isolates were studied.* July 2008: Phase I intervention programme
      Implementation of an antibiotic policy in the hospital.* July 2008 to June 2010:
      Assessment of the impact of the Phase I intervention programme.* July 2010 to
      March 2011: Phase II intervention programme: Formation and effective functioning
      of the antimicrobial stewardship committee. Statistical correlation of the
      Defined daily dose (DDD) for prescribed drugs with the antimicrobial resistance
      of Gram negatives. RESULTS: Phase I intervention programme (July 2008) resulted
      in a decrease of 4.47% in ESBLs (E.coli and Klebsiella) and a significant
      decrease of 40.8% in carbapenem-resistant Pseudomonas. Phase II intervention
      (July 2010) brought a significant reduction (24.7%) in carbapenem-resistant
      Pseudomonas. However, the resistance in the other Gram negatives (E.coli,
      Klebsiella, and Acinetobacter) rose and then stabilized. A positive correlation
      was observed in Pseudomonas and Acinetobacter with carbapenems and cefoperazone
      sulbactam.Piperacillin-tazobactam showed a positive correlation with
      Acinetobacter only. E.coli and Klebsiella showed positive correlation with
      cefoparazone-sulbactam and piperacillin-tazobactam. CONCLUSION: An antimicrobial
      stewardship programme with sustained and multifaceted efforts is essential to
      promote the judicious use of antibiotics.

PMID- 22958480
TI  - Social attention: a possible early indicator of efficacy in autism clinical
      trials.
AB  - For decades, researchers have sought to clarify the nature of the social
      communication impairments in autism, highlighting impaired or atypical 'social
      attention' as a key measurable construct that helps to define the core impairment
      of social communication. In this paper, we provide an overview of research on
      social attention impairments in autism and their relation to deficiencies in
      neural circuitry related to social reward. We offer a framework for considering
      social attention as a potential moderator or mediator of response to early
      behavioral intervention, and as an early indicator of efficacy of behavioral
      and/or pharmacological treatments aimed at addressing the social impairments in
      autism.

PMID- 22958483
TI  - Instrumental Activities of Daily Living (I-ADL) trigger an urgent request for
      nursing home admission.
AB  - OBJECTIVE: Although disabled elderly people mostly prefer to receive care at home
      or in other community settings, many of them reside in nursing homes. That is why
      several researchers have tried to identify predictors of institutionalisation.
      Various different dependency factors seem to explain the request for residential
      care. The aim of this study is to discover the most important factor triggering
      an urgent request for nursing home admission. METHODS: On the basis of social
      field research, we analysed the profiles and motives of an admission cohort of
      125 elderly (31 men and 94 women) who were admitted to four nursing homes in
      Antwerp (Belgium) between January 2000 and April 2001. The study used data of the
      'intake conversation', performed by an experienced social worker of the nursing
      home, subsequent to the request for nursing home admission.Gender, age, Katz
      category, marital status, disease, living conditions, Personal and Instrumental
      Activities of Daily Living (P-ADL and I-ADL) were the independent variables.The
      variable 'time span' was introduced as dependent variable. This is the time
      between the onset of dependency and the request for institutionalisation. Nursing
      home carers have classified this time span in three periods: < 3, 3-12, and > 12
      months. The statistical analysis focused on the characteristics of the two
      extremes, namely the earliest versus the latest applicants (n = 74). This was the
      best strategy to go about investigating the issue due to the vagueness and
      uncertain status of the data in the midrange. RESULTS: The applicants had an
      average age of 83 years. 31% of the elderly were defined as functioning good
      (needing assistance from another person in no to maximum two ADLs - washing and
      dressing) and 69% were classified as ill functioning (needing assistance in
      minimum three ADLs). Women were more likely to be widowed (83%) and to live alone
      and isolated (55%) and they had a lower degree of dependency (both P-ADL and I
      ADL) when entering institutions. Of the women, 57% had a mental illness, compared
      with 48% of the men. Of the applicants, 34% were unwilling or unable to start
      home care and applied for an urgent request (within the first 3 months); 41%
      tried home care for a time and 26% applied after one year of home care.The
      stepwise logistic regression analysis identified I-ADL as the decisive factor
      explaining the difference in 'decision speed' towards institutionalisation. An
      increase of one unit on the I-ADL score increased the chance of a request within
      the first three months by 63% (95%CI: 19 to135%, p = 0.006). CONCLUSIONS: The
      only factor related to an urgent request for nursing home admission seems to be
      the I-ADL score. These results have important implications for targeting
      sheltered housing and further extension of home care services to postpone or
      prevent institutionalisation.

PMID- 22958482
TI  - Impact of pre-existing MSP1(42)-allele specific immunity on potency of an
      erythrocytic Plasmodium falciparum vaccine.
AB  - BACKGROUND: MSP1 is the major surface protein on merozoites and a prime candidate
      for a blood stage malaria vaccine. Preclinical and seroepidemiological studies
      have implicated antibodies to MSP1 in protection against blood stage parasitaemia
      and/or reduced parasite densities, respectively. Malaria endemic areas have
      multiple strains of Plasmodium falciparum circulating at any given time, giving
      rise to complex immune responses, an issue which is generally not addressed in
      clinical trials conducted in non-endemic areas. A lack of understanding of the
      effect of pre-existing immunity to heterologous parasite strains may
      significantly contribute to vaccine failure in the field. The purpose of this
      study was to model the effect of pre-existing immunity to MSP142 on the
      immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles.
      METHODS: Inbred and outbred mice were immunized with various recombinant P.
      falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20
      (3D7) and Wellcome (K1, FVO). Humoral immune responses were analysed by ELISA and
      LuminexTM, and functional activity of induced MSP142-specific antibodies was
      assessed by growth inhibition assays. T-cell responses were characterized using
      ex vivo ELISpot assays. RESULTS: Analysis of the immune responses induced by
      various immunization regimens demonstrated a strong allele-specific response at
      the T cell level in both inbred and outbred mice. The success of heterologous
      regimens depended on the degree of homology of the N-terminal p33 portion of the
      MSP142, likely due to the fact that most T cell epitopes reside in this part of
      the molecule. Analysis of humoral immune responses revealed a marked cross
      reactivity between the alleles. Functional analyses showed that some of the
      heterologous regimens induced antibodies with improved growth inhibitory
      activities. CONCLUSION: The development of a more broadly efficacious MSP1 based
      vaccine may be hindered by clonally imprinted p33 responses mainly restricted at
      the T cell level. In this study, the homology of the p33 sequence between the
      clonally imprinted response and the vaccine allele determines the magnitude of
      vaccine induced responses.

PMID- 22958484
TI  - Podocytes and disease: introduction.

PMID- 22958485
TI  - Signaling from the podocyte intercellular junction to the actin cytoskeleton.
AB  - Observations of hereditary glomerular disease support the contention that
      podocyte intercellular junction proteins are essential for junction formation and
      maintenance. Genetic deletion of most of these podocyte intercellular junction
      proteins results in foot process effacement and proteinuria. This review focuses
      on the current understanding of molecular mechanisms by which podocyte
      intercellular junction proteins such as the nephrin-neph1-podocin-receptor
      complex coordinate cytoskeletal dynamics and thus intercellular junction
      formation, maintenance, and injury-dependent remodeling.

PMID- 22958487
TI  - The challenge and response of podocytes to glomerular hypertension.
AB  - Glomerular hypertension (ie, increased glomerular capillary pressure), has been
      shown to cause podocyte damage progressing to glomerulosclerosis in animal
      models. Increased glomerular capillary pressure results in an increase in wall
      tension that acts primarily as circumferential tensile stress on the capillary
      wall. The elastic properties of the glomerular basement membrane (GBM) and the
      elastic as well as contractile properties of the cytoskeleton of the endothelium
      and of podocyte foot processes resist circumferential tensile stress. Whether the
      contractile forces generated by podocytes are able to equal circumferential
      tensile stress to effectively counteract wall tension is an open question.
      Mechanical stress is transmitted from the GBM to the actin cytoskeleton of
      podocyte foot processes via cell-matrix contacts that contain mainly integrin
      alpha3beta1 and a variety of linker, scaffolding, and signaling proteins, which
      are not well characterized in podocytes. We know from in vitro studies that
      podocytes are sensitive to stretch, however, the crucial mechanosensor in
      podocytes remains unclear. On the other hand, in vitro studies have shown that in
      stretched podocytes specific signaling cascades are activated, the synthesis and
      secretion of various hormones and their receptors are increased, cell-cycle
      arrest is reinforced, cell adhesion is altered through secretion of matricellular
      proteins and changes in integrin expression, and the actin cytoskeleton is
      reorganized in a way that stress fibers are lost. In summary, current evidence
      suggests that in glomerular hypertension podocytes primarily aim to maintain the
      delicate architecture of interdigitating foot processes in the face of an
      expanding GBM area.

PMID- 22958486
TI  - Calcium regulates podocyte actin dynamics.
AB  - Ca(2+)-mediated remodeling of the actin cytoskeleton is a dynamic process that
      regulates cell motility through the modulation of rho guanosine triphosphatase
      (GTPase) signaling. Kidney podocytes are unique, pericyte-like cells with a
      complex cellular organization consisting of a cell body, major processes, and
      foot processes (FPs). The FPs form a characteristic interdigitating pattern with
      FPs of neighboring podocytes, leaving in between filtration slits that are
      covered by the slit diaphragm (SD). The actin-based FP and the SD form the final
      barrier to proteinuria. Mutations affecting several podocyte proteins cause
      disruption of the filtration barrier and rearrangement of the highly dynamic
      podocyte actin cytoskeleton. Proteins regulating the plasticity of the podocyte
      actin cytoskeleton are therefore of critical importance for sustained kidney
      barrier function. Dynamic regulation of the actin-based contractile apparatus in
      podocyte FPs is essential for sustained kidney filter function. Thus, the
      podocyte represents an excellent model system to study calcium signaling and
      actin dynamics in a physiologic context. Here, we discuss the regulation of
      podocyte actin dynamics by angiotensin or bradykinin-mediated calcium influx and
      downstream Rho GTPase signaling pathways and how these pathways are operative in
      other cells including fibroblasts and cancer cells.

PMID- 22958488
TI  - Role of the podocyte (and glomerular endothelium) in building the GBM.
AB  - This article summarizes the basic cellular and extracellular events in the
      development of the glomerulus and assembly of the glomerular basement membrane
      (GBM), paying special attention to laminin (LM) and type IV collagen. Cellular
      receptors for GBM proteins, including the integrins, dystroglycan, and discoidin
      domain receptor 1 also are discussed. Evidence is reviewed showing that the
      laminin isoform present in the earliest GBM, LM-111, and final isoform found in
      the mature GBM, LM-521, are each derived from both endothelial cells and
      podocytes. Although the early collagen alpha1alpha2alpha1(IV) similarly derives
      from endothelial cells and podocytes, collagen alpha3alpha4alpha5(IV) found in
      fully mature GBM is a product solely of podocytes. Genetic diseases affecting
      laminin and type IV collagen synthesis also are presented, with an emphasis on
      mutations to LAMB2 (Pierson syndrome) and COL4A3, COL4A4, and COL4A5 (Alport
      syndrome), and their experimental mouse models. Stress is placed on the assembly
      of a compositionally correct GBM for the acquisition and maintenance of
      glomerular barrier properties.

PMID- 22958489
TI  - Repair problems in podocytes: Wnt, Notch, and glomerulosclerosis.
AB  - Wnt/Ctnnb1 and Notch signaling play key roles in kidney development and
      epithelial cell specification. Recent reports have suggested that these pathways
      are reactivated in response to injury and in different disease conditions.
      Studies using genetically modified animal models showed that sustained activation
      of Notch and Wnt signaling in podocytes are causally related to albuminuria and
      glomerulosclerosis development. Here, we discuss the role and regulation of
      Wnt/Ctnnb1 and Notch signaling in podocytes.

PMID- 22958490
TI  - Parietal epithelial cells and podocytes in glomerular diseases.
AB  - In recent years, it has become apparent that parietal epithelial cells (PECs)
      play an important role within the renal glomerulus, in particular in diseased
      conditions. In this review, we examine current knowledge about the role of PECs
      and their interactions with podocytes in development and under physiological
      conditions. A particular focus is on the crucial role of PECs and podocytes in
      two major glomerular disease entities. In rapidly progressive glomerulonephritis,
      PECs and podocytes proliferate and obstruct the tubular outlet, resulting in loss
      of the affected nephron. In focal and segmental glomerulosclerosis, PECs become
      activated and invade a segment of the glomerular tuft via an adhesion. From this
      entry site, activated PECs displace podocytes and deposit matrix. Thus, activated
      PECs are involved in inflammatory as well as degenerative glomerular diseases,
      which both can lead to irreversible loss of renal function.

PMID- 22958491
TI  - TGF-beta/BMP pathways and the podocyte.
AB  - Renal fibrosis is the major determinant in progression of acute and chronic
      kidney diseases. Transforming growth factor-beta (TGF-beta) has been shown to be
      an important mediator of progressive fibrosis. Several studies have implicated
      that TGF-beta1 is involved in the tight balance of survival and apoptotic
      responses in podocytes that are Smad-dependent or independent. Bone morphogenic
      protein-7 (BMP-7), another member of the TGF-beta superfamily, has to date been
      involved primarily in kidney development and was described as an active blocker
      of TGF-beta-induced profibrotic effects. Here, we summarize the direct effects of
      these two cytokines on podocytes. We describe their involvement in podocyte
      survival and apoptosis pathways with the potential to modify the critical steps
      in podocyte apoptosis induction. Our group has analyzed the cross-talk of BMP-7
      and TGF-beta1 signaling in podocytes and we describe BMP-7 as a cytoprotective
      factor that could antagonize proapoptotic TGF-beta signals. In addition, we
      identified various extracellular and intracellular modifiers that can influence
      this sensitive cross-talk. On the basis of our work and the work of others we
      conclude that the balance of TGF-beta1 and BMP-7 signaling and involvement of
      extracellular and intracellular modifiers in these cascades are important parts
      of podocyte physiology and pathophysiology.

PMID- 22958492
TI  - The renin-angiotensin-aldosterone system in podocytes.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a critical role in kidney
      function and its inhibition reduces proteinuria and preserves kidney function in
      patients with chronic kidney disease. Recent studies have shown that podocytes
      generate many components of the RAAS and they express receptors of RAAS,
      including angiotensin II, mineralocorticoid, and prorenin receptors. Crucial
      functions of podocytes, such as contraction, apoptosis, autophagocytosis, and
      cytoskeletal organization, have been shown to be regulated by the angiotensin II
      type 1 receptors. An activation of the glomerular RAAS and protection from
      podocyte injury by RAAS inhibitors have been shown in many glomerular diseases.
      Exploring the interaction between the local RAAS and the signaling involved in
      RAAS activation in podocytes will lead to new therapeutic strategies of podocyte
      protection.

PMID- 22958494
TI  - How many ways can a podocyte die?
AB  - Podocytes are highly specialized epithelial cells that line the urinary surface
      of the glomerular capillary tuft. To maintain kidney filtration, podocytes oppose
      the high intraglomerular hydrostatic pressure, form a molecular sieve, secrete
      soluble factors to regulate other glomerular cell types, and provide synthesis
      and maintenance of the glomerular basement membrane. Impairment of any of these
      functions after podocyte injury results in proteinuria and possibly renal
      failure. Loss of glomerular podocytes is a key feature for the progression of
      renal diseases, and detached podocytes can be retrieved in the urine of patients
      with progressive glomerular diseases. Thus, the concept of podocyte loss as a
      hallmark of progressive glomerular disease has been widely accepted. However, the
      nature of events that promote podocyte detachment and whether detachment is
      preceded by any kind of podocyte cell death, such as apoptosis, necroptosis, or
      necrosis, still remains unclear and is discussed in this review.

PMID- 22958493
TI  - VEGF and podocytes in diabetic nephropathy.
AB  - Vascular endothelial growth factor-A (VEGF-A) is a protein secreted by podocytes
      that is necessary for survival of endothelial cells, podocytes, and mesangial
      cells. VEGF-A regulates slit-diaphragm signaling and podocyte shape via VEGF
      receptor 2-nephrin-nck-actin interactions. Chronic hyperglycemia-induced excess
      podocyte VEGF-A and low endothelial nitric oxide drive the development and the
      progression of diabetic nephropathy. The abnormal cross-talk between VEGF-A and
      nitric oxide pathways is fueled by the diabetic milieu, resulting in increased
      oxidative stress. Recent findings on these pathogenic molecular mechanisms
      provide new potential targets for therapy for diabetic renal disease.

PMID- 22958495
TI  - Socioeconomic disparities in the mental health of Indigenous children in Western
      Australia.
AB  - BACKGROUND: The burden of mental health problems among Aboriginal and Torres
      Strait Islander children is a major public health problem in Australia. While
      socioeconomic factors are implicated as important determinants of mental health
      problems in mainstream populations, their bearing on the mental health of
      Indigenous Australians remains largely uncharted across all age groups. METHODS:
      We examined the relationship between the risk of clinically significant emotional
      or behavioural difficulties (CSEBD) and a range of socioeconomic measures for
      3993 Indigenous children aged 4-17 years in Western Australia, using a
      representative survey conducted in 2000-02. Analysis was conducted using
      multivariate logistic regression within a multilevel framework. RESULTS: Almost
      one quarter (24%) of Indigenous children were classified as being at high risk of
      CSEBD. Our findings generally indicate that higher socioeconomic status is
      associated with a reduced risk of mental health problems in Indigenous children.
      Housing quality and tenure and neighbourhood-level disadvantage all have a strong
      direct effect on child mental health. Further, the circumstances of families with
      Indigenous children (parenting quality, stress, family composition, overcrowding,
      household mobility, racism and family functioning) emerged as an important
      explanatory mechanism underpinning the relationship between child mental health
      and measures of material wellbeing such as carer employment status and family
      financial circumstances. CONCLUSIONS: Our results provide incremental evidence of
      a social gradient in the mental health of Aboriginal and Torres Strait Islander
      children. Improving the social, economic and psychological conditions of families
      with Indigenous children has considerable potential to reduce the mental health
      inequalities within Indigenous populations and, in turn, to close the substantial
      racial gap in mental health. Interventions that target housing quality, home
      ownership and neighbourhood-level disadvantage are likely to be particularly
      beneficial.

PMID- 22958496
TI  - Six minute walking test: an old tool with new applications.

PMID- 22958497
TI  - One-step detection of Bean pod mottle virus in soybean seeds by the reverse
      transcription loop-mediated isothermal amplification.
AB  - BACKGROUND: Bean pod mottle virus (BPMV) is a wide-spread and destructive virus
      that causes huge economic losses in many countries every year. A sensitive,
      reliable and specific method for rapid surveillance is urgently needed to prevent
      further spread of BPMV. METHODS: A degenerate reverse-transcription loop-mediated
      isothermal amplification (RT-LAMP) primer set was designed on the conserved
      region of BPMV CP gene. The reaction conditions of RT-LAMP were optimized and the
      feasibility, specificity and sensitivity of this method to detect BPMV were
      evaluated using the crude RNA rapidly extracted from soybean seeds. RESULTS: The
      optimized RT-LAMP parameters including 6 mM MgCl2, 0.8 M betaine and temperature
      at 62.5-65 degrees C could successfully amplify the ladder-like bands from BPMV
      infected soybean seeds. The amplification was very specific to BPMV that no cross
      reaction was observed with other soybean viruses. Inclusion of a fluorescent dye
      makes it easily be detected in-tube by naked eye. The sensitivity of RT-LAMP
      assay is higher than the conventional RT-PCR under the conditions tested, and the
      conventional RT-PCR couldn't be used for detection of BPMV using crude RNA
      extract from soybean seeds. CONCLUSION: A highly efficient and practical method
      was developed for the detection of BPMV in soybean seeds by the combination of
      rapid RNA extraction and RT-LAMP. This RT-LAMP method has great potential for
      rapid BPMV surveillance and will assist in preventing further spread of this
      devastating virus.

PMID- 22958498
TI  - Successful MitraClipTM implantation in a 15-year-old patient with multiple prior
      cardiac surgeries.
AB  - Percutaneous edge-to-edge mitral valve repair using the MitraClip(TM) has not
      been used in children. The patient in this reported case was a 15-year-old male
      adolescent who presented postnatally with severe aortic valve stenosis and
      dysplasia of the mitral valve. The boy underwent surgical valvuloplasty at the
      age of 3 months and an aortoventriculoplasty with three re-operations. At the age
      of 15 years, he developed severe mitral valve regurgitation. Owing to high
      surgical risks, a MitraClip(TM) was implanted with a reduction of mitral
      regurgitation from grade 4+ to 2+, translating into a rapid clinical improvement.

PMID- 22958499
TI  - Factor VIIa-antithrombin complexes in patients with non-neoplastic portal vein
      thrombosis with and without cirrhosis.
AB  - INTRODUCTION: Portal vein thrombosis (PVT) is caused by local and systemic
      prothrombotic risk factors. In this case-control study, we evaluated the use of
      the Factor VIIa-antithrombin complex (FVIIa-AT) complex assay as a
      hypercoagulability marker in patients with PVT. METHODS: Two different groups of
      cases were considered: (i) n = 12 noncirrhotic PVT patients, (ii) n = 33
      cirrhotic patients with PVT. Controls were sex and age-matched healthy volunteers
      and cirrhotic subjects without PVT, respectively. RESULTS: Levels of the FVIIa-AT
      complex were significantly higher in noncirrhotic PVT subjects (132 +/- 32 pM)
      than in healthy volunteers (108 +/- 18 pM, P = 0.04). No significant difference
      in FVIIa-AT complexes was seen between cirrhotic patients with (64 +/- 20 pM) or
      without (61 +/- 24 pM) PVT. A linear correlation was seen between FVIIa-AT and
      FVIIa in noncirrhotic PVT subjects. In cirrhotic patients, FVIIa-AT complexes
      depended on both FVIIa and AT. CONCLUSION: These results confirm the utility of
      the FVIIa-AT assay in identifying the hypercoagulable state of noncirrhotic
      patients because of a previous thrombotic event.

PMID- 22958500
TI  - Current status and future perspectives for sequencing livestock genomes.
AB  - Only in recent years, the draft sequences for several agricultural animals have
      been assembled. Assembling an individual animal's entire genome sequence or
      specific region(s) of interest is increasingly important for agricultural
      researchers to perform genetic comparisons between animals with different
      performance. We review the current status for several sequenced agricultural
      species and suggest that next generation sequencing (NGS) technology with
      decreased sequencing cost and increased speed of sequencing can benefit
      agricultural researchers. By taking advantage of advanced NGS technologies, genes
      and chromosomal regions that are more labile to the influence of environmental
      factors could be pinpointed. A more long term goal would be addressing the
      question of how animals respond at the molecular and cellular levels to different
      environmental models (e.g. nutrition). Upon revealing important genes and gene
      environment interactions, the rate of genetic improvement can also be
      accelerated. It is clear that NGS technologies will be able to assist animal
      scientists to efficiently raise animals and to better prevent infectious diseases
      so that overall costs of animal production can be decreased.

PMID- 22958501
TI  - Effect of dietary stable isotopic ratios of carbon and nitrogen on the extent of
      their incorporation into tissues of rats.
AB  - This study was conducted to investigate the effect of different dietary ratios
      of 13 C to 12 C or 15 N to 14 N on their relative incorporation into tissues.
      Eighty male rats were used in two 21-day feeding trials in which they were fed
      diets with either high delta13C levels (delta13C = -13.890/00 and delta15N =
      2.370/00 in experiment 1 and delta13C = -19.340/00 and delta15N = 4.730/00 in
      experiment 2) or low delta13C levels (delta13C = -17.900/00 and delta15N =
      3.080/00 in experiment 1 and delta13C = -21.760/00 and delta15N = 0.530/00 in
      experiment 2), meanwhile, the dietary delta15N levels were designed to two ranks.
      Blood, liver, adipose and muscle tissues were collected on day 0, 3, 7, 14, and
      21 for determination of 13 C, 12 C, 15 N and 14 N isotopes. Rat growth rate,
      antioxidant capacity and metabolic parameters were also assessed. The results
      indicate that adipose tissue tend to deplete 13 C before the stable isotopic
      ratios achieved final equilibrium. Therefore, feeds with different isotopic
      signatures had different incorporation rates into tissues. Low dietary 13 C
      levels decreased tissue delta13C values whereas high dietary 13 C levels did not
      alter tissue delta13C values during the 21-d experiment. Blood delta15N values
      were a reliable parameter in assessing the relative contribution of dietary
      nitrogen to tissues. This study revealed a relationship between dietary isotopic
      signatures and their incorporation rates into rat tissues. However, more studies
      are needed to illustrate the mechanism through which dietary isotopic ratios
      influence the extent of isotopic incorporation into the tissues.

PMID- 22958502
TI  - JAK2 V617F mutation negative erythrocytosis (or how to more simply perform
      diagnosis and treat a patient with increased hematocrit).
AB  - SUMMARY: This case report focuses on a 71-year old patient affected by unknown
      dyspnea and erythrocytosis referred by his general practitioner to our center for
      specialist advice after a hematological examination had excluded polycythemia
      vera on grounds of negative test for JAK2 V617F/exon 12 mutation. An accurate
      clinical history and physical examination accompanied by respiratory function
      tests resulted in diagnosis of JAK2 V617F mutation negative erythrocytosis, and
      treatment could be started. The discussion examines decisional algorithms when a
      polyglobulic patient is referred for diagnosis.

PMID- 22958503
TI  - Dietary exposure assessments for children in europe (the EXPOCHI project):
      rationale, methods and design.
AB  - BACKGROUND/PURPOSE: The number of dietary exposure assessment studies focussing
      on children is very limited. Children are however a vulnerable group due to their
      higher food consumption level per kg body weight. Therefore, the EXPOCHI project
      aims 1 to create a relational network of individual food consumption databases in
      children, covering different geographical areas within Europe, and 2 to use these
      data to assess the usual intake of lead, chromium, selenium and food colours.
      METHODS: EXPOCHI includes 14 food consumption databases focussed on children (1
      14 y old). The data are considered representative at national/regional level: 14
      regions covering 13 countries. Since the aim of the study is to perform long-term
      exposure assessments, only data derived from 24 hr dietary recalls and dietary
      records recorded on at least two non-consecutive days per individual were
      included in the dietary exposure assessments. To link consumption data and
      concentration data of lead, chromium and selenium in a standardised way,
      categorisation of the food consumption data was based on the food categorisation
      system described within the SCOOP Task report 3.2.11. For food colours, the food
      categorisation system specified in the Council Directive 94/36/EC was used.
      CONCLUSION: The EXPOCHI project includes a pan-European long-term exposure
      assessment of lead, chromium, selenium and food colours among children living in
      13 different EU countries. However, the different study methods and designs used
      to collect the data in the different countries necessitate an in-depth
      description of these different methods and a discussion about the resulting
      limitations.

PMID- 22958504
TI  - What is the optimal fluid status in critically ill patients?

PMID- 22958505
TI  - Naturalistic outcome of treatment of psychosis by traditional healers in Jinja
      and Iganga districts, Eastern Uganda - a 3- and 6 months follow up.
AB  - OBJECTIVE: To determine the naturalistic outcome of treatment of psychosis by
      traditional healers in Jinja and Iganga districts of Eastern Uganda. METHOD: A
      cohort of patients with psychosis receiving treatment from traditional healers'
      shrines were recruited between January and March 2008 and followed up at three
      and six months. The Mini International Neuropsychiatry Interview (MINI Plus) was
      used for making specific diagnosis at the point of contact. For specific
      symptoms, Positive and Negative Symptom Scale (PANSS), Young Mania Rating Scale
      (YMRS) and Montgomery Asberg Depression Rating Scale (MADRS) were used to measure
      severity of schizophrenia, mania and psychotic depression, respectively. The
      Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) were
      used for objective assessments. The Compass Mental Health Index measured well
      being. Mean scores of the scales were computed using one way ANOVA for
      independent samples. Associations between outcome and categorical variables were
      examined at bivariate and multivariate levels. RESULTS: All the symptom scales
      had a percentage reduction of more than 20% at three and six months follow up.
      The differences between the mean scores of the scales at baseline and 3 months,
      baseline and 6 months, and 3 and 6 months were all significant (P < 0.0001). The
      post test for pair wise comparisons, the Tukey HSD (Honestly Significant
      Difference) test was also all significant at P < 0.01 except for MADRS where
      there was no significant difference between 3 and 6 months for depression
      severity. Over 80% of the participants used biomedical services for the same
      symptoms in the study period. At 3 months follow up, patients who combined
      treatment were less likely to be cases (P = 0.002; OR 0.26 [0.15-0.58]), but more
      likely to be cases at 6 months follow up (P = 0.020; OR 2.05 [1.10-3.189]). Being
      in debt was associated with caseness both at 3 and 6 months. CONCLUSION: This
      study suggests that there may be some positive effects for patients with
      psychosis who combine both biomedical services and traditional healing. Further
      research in the area of naturalistic outcome of traditional healing is necessary.

PMID- 22958506
TI  - Reduced social preferences in autism: evidence from charitable donations.
AB  - BACKGROUND: People with autism have abnormal preferences, ranging from an
      apparent lack of preference for social stimuli to unusually strong preferences
      for restricted sets of highly idiosyncratic stimuli. Yet the profile of
      preferences across social and nonsocial domains has not been mapped out in
      detail, and the processes responsible remain poorly understood. METHODS: To
      assess preferences across a range of stimuli, we measured real monetary donations
      to 50 charities spanning categories pertaining to people, mental health, animals,
      or the environment. We compared the donations made by 16 high-functioning adults
      with autism to those made by neurotypical controls matched on age, gender and
      education. We additionally collected ratings of how people evaluated the
      different charities. RESULTS: Compared with controls, high-functioning adults
      with autism donated less overall and also showed a significantly disproportionate
      reduction in donations to people charities compared with donations to the other
      charities. Furthermore, whereas controls discriminated strongly between different
      people charities, choosing to donate a lot of money to some and very little to
      others, much less discrimination was seen in the autism group. Ratings that
      probed how participants constructed their preferences did not differ between
      groups, except for a difference in the perceived impact of pictures and text
      information about people charities. Strikingly, there were some charities related
      to mental health, and autism in particular, to which the autism group donated
      considerably more than did the controls. CONCLUSIONS: People with autism were
      found to have reduced preference and sensitivity towards charities benefiting
      other people. The findings provide evidence for a domain-specific impairment in
      social cognition in autism spectrum disorder, and in particular in linking
      otherwise intact social knowledge to the construction of value signals on which
      preferences regarding other people are based.

PMID- 22958507
TI  - Effectiveness of water physical therapy on pain, pressure pain sensitivity, and
      myofascial trigger points in breast cancer survivors: a randomized, controlled
      clinical trial.
AB  - OBJECTIVE: To evaluate the effects of an 8-week water physical therapy program on
      cervical and shoulder pain, pressure sensitivity, and the presence of trigger
      points (TrPs) in breast cancer survivors. DESIGN: Randomized, controlled trial.
      SETTING: To date, no study has investigated effects of water therapy in breast
      cancer. PATIENTS: Sixty-six breast cancer survivors were randomly assigned into
      two groups: WATER group, who received a water exercise program or CONTROL group
      who received the usual care treatment for breast cancer. INTERVENTIONS: The WATER
      therapy program consisted of 24 sessions (3 times/week over 8 weeks) of low
      intensity exercises in a warm pool (32 degrees C). Each session included 10
      minute warm-up period; 35 minutes of aerobic, low-intensity endurance, and core
      stability training; and a 15-minute cool-down period (stretching and relaxation).
      OUTCOMES:  Neck and shoulder pain (visual analog scale, 0-100 mm), pressure pain
      thresholds (PPTs) over C5-C6 zygapophyseal joints, deltoid muscles, second
      metacarpal, and tibialis anterior muscles, and the presence of TrPs in cervical
      shoulder muscles were assessed at baseline and after the 8-week program by an
      assessor blinded to treatment allocation. RESULTS: The WATER group demonstrated a
      between-group improvement for neck pain of -31 mm (95% confidence interval [CI]
      49 to -22, P < 0.001; effect size 1.1, 0.81-1.75) and for shoulder-axillary of 
      19 mm (-40 to -04, P = 0.046; effect size 0.70, 0.14-1.40). Improvements were
      also noted for PPT levels over C5-C6 joints (between-group differences, affected
      side: 27.7 kPa, 95% CI 3.9-50.4; unaffected: 18.1 kPa, 95% CI 6.1-52.2). No
      between-group differences for PPT over the remaining points were observed (P >
      0.05). Finally, patients in the WATER program showed a greater reduction of
      active TrPs as compared with the CONTROL group (P < 0.05). CONCLUSIONS:  An 8
      week water therapy program was effective for improving neck and shoulder/axillary
      pain, and reducing the presence of TrPs in breast cancer survivors as compared
      with usual care; however, no significant changes in widespread pressure pain
      hyperalgesia were found.

PMID- 22958508
TI  - Case report and evaluation of the frequency of the prozone phenomenon in syphilis
      serology - an infrequent but important laboratory phenomenon.
AB  - BACKGROUND: Treponema pallidum specific serology generally remains reactive for
      life. Therefore, the diagnosis of syphilis reinfection relies on clinical
      assessment and nontreponemal (reagin) serologic testing. The prozone phenomenon
      can lead to a falsely nonreactive rapid plasma reagin (RPR) assay result.
      METHODS: We report a case of secondary syphilis in a HIV infected patient with a
      previous history of syphilis infection, where a falsely nonreactive RPR assay was
      associated with a delayed diagnosis of reinfection and infectious syphilis. The
      prozone phenomenon was detected in several of the patient's serum samples
      collected around this time. We subsequently undertook a prospective evaluation
      for the prozone phenomenon in 3222 consecutive sera, which were assayed using the
      RPR assay for clinical purposes over a 10-month period. RESULTS: The overall rate
      of the prozone phenomenon was 2 out of 3222 samples (0.06%; 95% confidence
      interval (CI): 0.02-0.22%) and the rate per reactive sample was 2 out of 397
      (0.5%; 95% CI: 0.14-1.81%). CONCLUSION: Clinicians should request RPR testing at
      dilutions of sera when syphilis is suspected clinically and the RPR assay is
      nonreactive.

PMID- 22958509
TI  - The step from a voluntary to a mandatory national nosocomial infection
      surveillance system: the influence on infection rates and surveillance effect.
AB  - BACKGROUND: The German national nosocomial infection surveillance system, KISS,
      has a component for very low birth weight (VLBW) infants (called NEO-KISS) which
      changed from a system with voluntary participation and confidential data feedback
      to a system with mandatory participation and confidential feedback. METHODS: In
      order to compare voluntary and mandatory surveillance data, two groups were
      defined by the surveillance start date. Neonatal intensive care unit (NICU)
      parameters and infection rates of the NICUs in both groups were compared. In
      order to analyze the surveillance effect on primary bloodstream infection rates
      (BSI), all VLBW infants within the first three years of participation in both
      groups were considered. The adjusted effect measures for the year of
      participation were calculated. RESULTS: An increase from 49 NICUs participating
      in 2005 to 152 in 2006 was observed after the introduction of mandatory
      participation. A total of 4280 VLBW infants was included in this analysis.
      Healthcare-associated incidence densities rates were similar in both groups.
      Using multivariate analysis with the endpoint primary BSI rate and comparing the
      first and third year of participation lead to an adjusted incidence rate ratio
      (IRR) of 0.78 (CI95 0.66-0.93) for old (voluntary) and 0.81 (CI95 0.68-0.97) for
      new (mandatory) participants. CONCLUSIONS: The step from a voluntary to a
      mandatory HCAI surveillance system alone may lead to substantial improvements on
      a countrywide scale.

PMID- 22958510
TI  - Comparison of spatial working memory in children with prenatal alcohol exposure
      and those diagnosed with ADHD; A functional magnetic resonance imaging study.
AB  - BACKGROUND: Alcohol related neurodevelopmental disorder (ARND) falls under the
      umbrella of fetal alcohol spectrum disorder (FASD), but individuals do not
      demonstrate the facial characteristics associated with fetal alcohol syndrome
      (FAS), making diagnosis difficult. While attentional problems in ARND are similar
      to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying
      impairment in attention pathways may be different. METHODS: Functional magnetic
      resonance imaging (fMRI) of a working memory (1-back) task of 63 children, 10 to
      14 years old, diagnosed with ARND and ADHD, as well as typically developing (TD)
      controls, was conducted at 3 T. Diffusion tensor imaging (DTI) data were also
      acquired. RESULTS: Activations were observed in posterior parietal and occipital
      regions in the TD group and in dorsolateral prefrontal and posterior parietal
      regions in the ARND group, whereas the ADHD group activated only dorsolateral
      prefrontal regions, during the working memory component of the task (1-back minus
      0-back contrast). The increases in frontal and parietal activity were
      significantly greater in the ARND group compared to the other groups. This
      increased activity was associated with reduced accuracy and increased response
      time variability, suggesting that ARND subjects exert greater effort to manage
      short-term memory load. Significantly greater intra-subject variability,
      demonstrated by fMRI region-of-interest analysis, in the ADHD and ARND groups
      compared to the TD group suggests that moment-to-moment lapses in attention
      contributed to their poorer task performance. Differences in functional activity
      in ARND subjects with and without a diagnosis of ADHD resulted primarily from
      reduced activation by the ARND/ADHD + group during the 0-back task. In contrast,
      children with ADHD alone clearly showed reduced activations during the 1-back
      task. DTI analysis revealed that the TD group had significantly higher total
      tract volume and number of fibers than the ARND group. These measures were
      negatively correlated with errors on the 1-back task, suggesting a link between
      white matter integrity and task performance. CONCLUSIONS: fMRI activations
      suggest that the similar behavior of children with ARND and ADHD on a spatial
      working memory task is the result of different cognitive events. The nature of
      ADHD in children with ARND appears to differ from that of children with ADHD
      alone.

PMID- 22958511
TI  - An overview of the European Health Examination Survey Pilot Joint Action.
AB  - BACKGROUND: Health Examination Surveys (HESs) can provide essential information
      on the health and health determinants of a population, which is not available
      from other data sources. Nevertheless, only some European countries have systems
      of national HESs. A study conducted in 2006-2008 concluded that it is feasible to
      organize national HESs using standardized measurement procedures in nearly all EU
      countries. The feasibility study also outlined a structure for a European Health
      Examination Survey (EHES), which is a collaboration to organize standardized HESs
      in countries across Europe.To facilitate setting up national surveys and to gain
      experience in applying the EHES methods in different cultures, EHES Joint Action
      (2010-2011) planned and piloted standardized HESs in the working age population
      in 12 countries. This included countries with earlier national HESs and countries
      which were planning their first national HES. The core measurements included in
      all surveys were weight, height, waist circumference and blood pressure, and
      blood samples were taken to measure lipid profiles and glucose or glycated
      haemoglobin (HbA1c). These are modifiable determinants of major chronic diseases
      not identified in health interview surveys. There was a questionnaire to
      complement the data on the examination measurements. METHODS: Evaluation of the
      pilot surveys was based on review of national manuals and evaluation reports of
      survey organizers; observations and discussions of survey procedures during site
      visits and training seminars; and other communication with the survey organizers.
      RESULTS: Despite unavoidable differences in the ways HESs are organized in the
      various countries, high quality and comparability of the data seems achievable.
      The biggest challenge in each country was obtaining high participation rate. Most
      of the pilot countries are now ready to start their full-size national HES, and
      six of them have already started. CONCLUSIONS: The EHES Pilot Project has set up
      the structure for obtaining comparable high quality health indicators on health
      and important modifiable risk factors of major non-communicable diseases from the
      European countries. The European Union is now in a key position to make this
      structure sustainable. The EHES core survey can be expanded to cover other
      measurements.

PMID- 22958512
TI  - Asthma in pregnancy.

PMID- 22958513
TI  - A rising tide of blue-absorbing biliprotein photoreceptors: characterization of
      seven such bilin-binding GAF domains in Nostoc sp. PCC7120.
AB  - Cyanobacteriochromes are photochromic sensory photoreceptors in cyanobacteria
      that are related to phytochromes but cover a much broader spectral range. Using a
      homology search, a group of putative blue-absorbing photoreceptors was identified
      in Nostoc sp. PCC 7120 that, in addition to the canonical chromophore-binding
      cysteine of cyanobacteriochromes, have a conserved extra cysteine in a DXCF
      motif. To assess their photochemical activities, putative chromophore-binding GAF
      domains were expressed in Escherichia coli together with the genes for
      phycocyanobilin biosynthesis. All except one covalently bound a chromophore and
      showed photoreversible photochromic responses, with absorption at approximately
      420 nm for the 15Z states formed in the dark, and a variety of red-shifted
      absorption peaks in the 490-600 nm range for the 15E states formed after light
      activation. Under denaturing conditions, the covalently bound chromophores were
      identified as phycocyanobilin, phycoviolobilin or mixtures of both. The canonical
      cysteines and those of the DXCF motifs were mutated, singly or together. The
      canonical cysteine is responsible for stable covalent attachment of the bilin to
      the apo-protein at C3(1) . The second linkage from the cysteine in the DXCF
      motif, probably to C10 of the chromophore, yields blue-absorbing rubin-type 15Z
      chromophores, but is lost in most cases upon photoconversion to the 15E isomers
      of the chromophores, and also when denatured with acidic urea.

PMID- 22958515
TI  - Mode vibrations of a matrix transducer for three-dimensional second harmonic
      transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) uses the esophagus as an imaging window to
      the heart. This enables cardiac imaging without interference from the ribs or
      lungs and allows for higher frequency ultrasound to be used compared with
      transthoracic echocardiography (TTE). TEE facilitates the successful imaging of
      obese or elderly patients, where TTE may be unable to produce images of
      satisfactory quality. Recently, three-dimensional (3-D) TEE has been introduced,
      which greatly improves the image quality and diagnostic value of TEE by adding an
      extra dimension. Further improvement could be achieved by optimizing 3-D TEE for
      harmonic imaging. This article describes the optimal geometry and element
      configuration for a matrix probe for 3-D second harmonic TEE. The array concept
      features separated transmit and receive subarrays. The element geometry was
      studied using finite element modeling and a transmit subarray prototype was
      examined both acoustically and with laser interferometry. The transmit subarray
      is suitable for its role, with a 3 MHz resonance frequency, a 40%-50% -3 dB
      bandwidth and crosstalk levels <-27 dB. The proposed concept for the receive
      subarray has a 5.6 MHz center frequency and a 50% -3 dB bandwidth.

PMID- 22958516
TI  - Perspective on long term oxygen therapy.

PMID- 22958514
TI  - The global pipeline of new medicines for the control and elimination of malaria.
AB  - Over the past decade, there has been a transformation in the portfolio of
      medicines to combat malaria. New fixed-dose artemisinin combination therapy is
      available, with four different types having received approval from Stringent
      Regulatory Authorities or the World Health Organization (WHO). However, there is
      still scope for improvement. The Malaria Eradication Research agenda identified
      several gaps in the current portfolio. Simpler regimens, such as a single-dose
      cure are needed, compared with the current three-day treatment. In addition, new
      medicines that prevent transmission and also relapse are needed, but with better
      safety profiles than current medicines. There is also a big opportunity for new
      medicines to prevent reinfection and to provide chemoprotection. This study
      reviews the global portfolio of new medicines in development against malaria, as
      of the summer of 2012. Cell-based phenotypic screening, and 'fast followers' of
      clinically validated classes, mean that there are now many new classes of
      molecules starting in clinical development, especially for the blood stages of
      malaria. There remain significant gaps for medicines blocking transmission,
      preventing relapse, and long-duration molecules for chemoprotection. The nascent
      pipeline of new medicines is significantly stronger than five years ago. However,
      there are still risks ahead in clinical development and sustainable funding of
      clinical studies is vital if this early promise is going to be delivered.

PMID- 22958517
TI  - No additional copies of HERV-Fc1 in the germ line of multiple sclerosis patients.
AB  - BACKGROUND: Human endogenous retroviruses (HERVs) are suspected to play a role in
      the development of multiple sclerosis (MS). This suspicion has in part been based
      on increased expression of viral RNA or proteins or antibodies targeting
      retroviral products in MS patients. Recently, our group provided genetic evidence
      for association between the endogenous retrovirus HERV-Fc1 and MS, suggesting
      that HERV-Fc1 plays a role in this multifactorial disease. We have found
      increased expression of HERV-Fc1 in MS patients suffering from recent attack, but
      the underlying mechanism for association is still unknown. FINDINGS: Evidence
      from animal models indicates that ERV implication in the pathogenesis of diseases
      can be a result of extra copies of the virus in the germ line. Therefore, we
      investigated the genome of 81 individuals, 74 patients with MS and 7 healthy
      controls, by means of Southern blotting, for presence of extra HERV-Fc1 copies.
      The known insertion at the Xq21.33 position was readily detectable, but no
      additional insertions in other genomic contexts could be identified in any
      studied individuals. This substantiates our previous copy-number PCR findings of
      a 2:1 ratio of HERV-Fc1 DNA between women and men, as expected from the X
      chromosome location; there was no difference between patient and control
      individuals. CONCLUSIONS: No additional germ line copies of HERV-Fc1 could be
      identified, precluding such copies to underlie the association between this
      provirus and multiples sclerosis.

PMID- 22958518
TI  - Tissue expression and developmental regulation of chicken cathelicidin
      antimicrobial peptides.
AB  - Cathelicidins are a major family of antimicrobial peptides present in vertebrate
      animals with potent microbicidal and immunomodulatory activities. Four
      cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been
      identified in chickens. As a first step to understand their role in early innate
      host defense of chickens, we examined the tissue and developmental expression
      patterns of all four cathelicidins. Real-time PCR revealed an abundant expression
      of four cathelicidins throughout the gastrointestinal, respiratory, and
      urogenital tracts as well as in all primary and secondary immune organs of
      chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with
      the highest expression in the bone marrow and lung, while cathelicidin B1 was
      synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue
      specific regulatory pattern was evident for all four cathelicidins during the
      first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age
      dependent increase both in the cecal tonsil and lung, whereas all four
      cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual
      decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3
      was also observed in the cecum on day 28, while the highest expression of
      cathelicidin B1 was seen in both the lung and cecal tonsil on day 14.
      Collectively, the presence of cathelicidins in a broad range of tissues and their
      largely enhanced expression during development are suggestive of their potential
      important role in early host defense and disease resistance of chickens.

PMID- 22958519
TI  - Symptoms of respiratory tract infection and associated care-seeking in subjects
      with and without obstructive lung disease; the Tromso Study: Tromso 6.
AB  - BACKGROUND: Respiratory tract infections (RTIs) may be more severe in those with
      asthma or COPD and these patients are more frequently in need of health care. The
      aim of the study was to describe the frequency of RTI symptoms in a general adult
      population and how care-seeking is associated with the presence of obstructive
      lung disease. METHODS: Cross-sectional data including spirometry and self
      reported chronic diseases were collected among middle-aged and elderly subjects
      in the Tromso population survey (Tromso 6). Self- reported RTI symptoms,
      consultations and antibiotic use were the main outcome variables. Possible
      predictors of RTI symptoms were evaluated by multivariable logistic regression.
      RESULTS: Of the 6414 subjects included, 798 (12.4%) reported RTI symptoms in the
      previous week. RTI symptoms were reported less frequently by subjects aged 75
      years or above, than by those younger than 55 years (OR 0.5). Winter season (OR
      1.28), current smoking (OR 1.60), low self-rated health (OR 1.26) and moderate to
      severe bronchial obstruction (OR 1.51), were also statistically significant
      independent predictors of RTI symptoms, but these variables did not predict RTI
      symptoms that had started within the previous seven days. Among subjects with RTI
      symptoms, 5.1% also reported a consultation with a doctor. In those with
      bronchial obstruction by spirometry, who did not report asthma or COPD, this
      frequency was 2.4%. Antibiotic treatment was reported by 7.4% of the
      participants, among whom one third had consulted a doctor. Antibiotics were taken
      more frequently when asthma or COPD was reported (13.7%), but not in subjects
      with bronchial obstruction who did not report these diseases (7.2%). CONCLUSIONS:
      RTI symptoms seldom led to consultation with a doctor and not even in subjects
      with obstructive lung disease. This was in particular the case in subjects who
      did not know about their obstructive lung disease. Strategies for early diagnosis
      of COPD and providing health care to subjects with such disease cannot rely on
      their doctor visits due to respiratory symptoms.

PMID- 22958520
TI  - Translation and adaption of the interRAI Suite to local requirements in Belgian
      hospitals.
AB  - BACKGROUND: The interRAI Suite contains comprehensive geriatric assessment tools
      designed for various healthcare settings. Although each instrument is developed
      for a particular population, together they form an integrated health evaluation
      system. The interRAI Acute Care Minimum Data Set (interRAI AC) is tailored for
      hospitalized older persons. Our aim in this study was to translate and adapt the
      interRAI AC to the Belgian hospital context, where it can be used together with
      the interRAI Home Care (HC) and the interRAI Long Term Care Facility (LTCF).
      METHODS: A systematic, comprehensive, and rigorous 10-step approach was used to
      adapt the interRAI AC to local requirements. After linguistic translation by an
      official translator, five researchers assessed the translation for appropriate
      hospital jargon. Three researchers double-checked for translation accuracy and
      proposed additional items. A provisional version was converted into the three
      official languages of Belgium-Flemish, French, and German. Next, a
      multidisciplinary panel of nine experts judged item relevance to the Belgian care
      context and advised which country-specific items should be added. After these
      suggestions were incorporated into the interRAI AC, hospital staff from nine
      Flemish hospitals field-tested the tool in their practice. After evaluating field
      test results, we compared the interRAI AC with Belgian versions of the interRAI
      HC and interRAI LTCF. Next, the Flemish, French, and German versions of the
      Belgian interRAI portfolio were harmonized. Finally, we submitted the Belgian
      interRAI AC to the interRAI organization for ratification. RESULTS: Eighteen
      administrative items of the interRAI AC were adapted to the Belgian healthcare
      context (e.g., usual residence, formal community services prior to admission).
      Fourteen items assessing the 'informal caregiver', and 17 items, including
      country-specific items, were added (e.g., advanced directive for euthanasia).
      CONCLUSIONS: The interRAI AC was adapted to local requirements using a meticulous
      and recursive 10-step approach. As use of the interRAI Suite continues to grow
      worldwide and as it continues to expand to other care settings and populations,
      this procedure can guide future translations. This procedure might also be used
      by others facing similar challenges of complex translation and adaptation
      situations, where multidimensional instruments are used across multiple care
      settings in multiple languages.

PMID- 22958521
TI  - When working is not enough: food insecurity in the Canadian labour force.
AB  - OBJECTIVE: Food insecurity, lack of access to food due to financial constraints,
      is highly associated with poor health outcomes. Households dependent on social
      assistance are at increased risk of experiencing food insecurity, but food
      insecurity has also been reported in households reporting their main source of
      income from employment/wages (working households). The objective of the present
      study was to examine the correlates of food insecurity among households reliant
      on employment income. DESIGN: Working households reporting food insecurity were
      studied through analysis of the Canadian Community Health Survey, 2007-2008,
      employing descriptive statistics and logistic regression. Food insecurity was
      measured using the Household Food Security Survey Module; all provinces
      participated. SETTING: Canada. SUBJECTS: Canadian households where main income
      was derived through labour force participation. Social assistance recipients were
      excluded. RESULTS: For the period 2007-2008, 4% of working households reported
      food insecurity. Canadian households reliant on primary earners with less
      education and lower incomes were significantly more likely to experience food
      insecurity; these differences were accentuated across some industry sectors.
      Residence in Quebec was protective. Working households experiencing food
      insecurity were more likely to include earners reporting multiples jobs and
      higher job stress. Visible minority workers with comparable education levels
      experienced higher rates of food insecurity than European-origin workers.
      CONCLUSIONS: Reliance on employment income does not eliminate food insecurity for
      a significant proportion of households, and disproportionately so for households
      with racialized minority workers. Increases in work stress may increase the
      susceptibility to poor health outcomes of workers residing in households
      reporting food insecurity.

PMID- 22958522
TI  - Effects of the standardized ileal digestible lysine to metabolizable energy ratio
      on performance and carcass characteristics of growing-finishing pigs.
AB  - A total of 2,121 growing-finishing pigs (Duroc * Landrace * Large White) were
      utilized in six experiments conducted to determine the effects of different
      ratios of standardized ileal digestible lysine (SID-Lys) to metabolizable energy
      (ME) on the performance and carcass characteristics of growing-finishing pigs.
      Exps. 1 (30 to 50 kg), 2 (52 to 70 kg) and 3 (81 to 104 kg) were conducted to
      find an optimum ME level and then this level was used in Exps. 4 (29 to 47 kg), 5
      (54 to 76 kg) and 6 (84 to 109 kg) to test the response of pigs to different
      ratios of SID-Lys:ME. In Exps.1 to 3, four treatments were used consisting of
      diets with a formulated ME content of 3.1, 3.2, 3.3 or 3.4 in Exps. 1 and 2 while
      Exp. 3 used 3.05, 3.15, 3.25 or 3.35 Mcal/kg. A constant SID-Lys:ME ratio of 2.6,
      2.3 or 2.0 g/Mcal was used in Exps. 1, 2 and 3, respectively. Weight gain was
      significantly increased with increasing energy level in Exp.1 while weight gain
      was unaltered in Exps. 2 and 3. For all three experiments, feed intake was
      decreased (P < 0.05) and feed efficiency was improved (P < 0.05) with increasing
      energy level. Tenth rib back fat thickness linearly increased (P < 0.05) with
      increasing energy level. In Exps. 4 to 6, five treatments were used consisting of
      diets with a SID-Lys:ME ratio of 2.4, 2.6, 2.8, 3.0 or 3.2 in Exp. 1, 2.1, 2.3,
      2.5, 2.7, 2.9 or 3.2 in Exp. 2 and 1.8, 2.0, 2.2, 2.4, or 2.6 in Exp. 3. A
      constant ME level 3.2, 3.2 and 3.05 Mcal/kg was used in Exps. 1, 2 and 3,
      respectively (selected based on the results of weight gain). For all three
      experiments, weight gain increased (P < 0.05) and feed efficiency improved
      linearly (P < 0.05) as the SID-Lys:ME ratio increased. Tenth rib back fat
      thickness linearly decreased (P < 0.05) as the SID-Lys:ME ratio increased. Based
      on a straight broken-line model, the estimated SID-Lys:ME ratio to maximize
      weight gain was 3.0, 2.43 and 2.2 for 29 to 47, 54 to76 and 84 to 109 kg of pigs,
      respectively.

PMID- 22958523
TI  - Prognostic significance of thymidylate synthase polymorphisms in rectal cancer
      patients treated with neoadjuvant chemoradiotherapy.
AB  - AIM: There is a lack of prognostic factors of preoperative chemoradiation for
      locally advanced rectal cancer. Thymidylate synthase (TS) is the most important
      target of 5-fluorouracil; three main genetic polymorphisms of TS have been
      described. We analysed the prognostic value of these in patients with locally
      advanced rectal cancer treated with fluoropyrimidine-based chemoradiation.
      METHOD: Ninety-nine patients treated between November 2001 and March 2009 were
      included. All were treated by radiotherapy (5040 cGy) and concomitant
      fluoropyrimidine-based chemotherapy. Three polymorphisms were analysed: (i) a
      double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream
      of the ATG codon initiation site in the 5'-terminal regulatory region, (ii) a
      functional G > C single nucleotide polymorphism present in the second repeat of
      the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3'
      untranslated region. DNA was extracted from paraffin-embedded core biopsies taken
      from the tumour and the genotype was analysed using polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: The 6 bp polymorphism was
      significantly associated with disease-free survival (+ 6 bp/+ 6 bp vs-6 bp/-6 bp,
      P = 0.032 logistic regression). No differences were found in disease-free
      survival according to the other polymorphisms studied. No relationship was
      observed between the different TS genotypes and pathological regression.
      CONCLUSION: The study suggests that the TS 6 bp polymorphism may be a predictor
      of disease-free survival in patients with locally advanced rectal cancer treated
      with fluoropyrimidine-based chemoradiation.

PMID- 22958524
TI  - Angiogenesis in prostate cancer: onset, progression and imaging.
AB  - What's known on the subject? and What does the study add? Today, angiogenesis is
      known to play a key role in cancer growth and development. Emerging cancer
      treatments are based on the suppression of angiogenesis, and modern imaging
      techniques investigate changes in the microvasculature that are caused by
      angiogenesis. As for other forms of cancers, angiogenesis is well recognised as a
      fundamental process in the development of prostate cancer. The novelty of this
      extensive report on angiogenesis in cancer, with particular attention on prostate
      cancer and the imaging techniques able to detect it, is the new prospective to
      the subject. In contrast with the other available reviews, this report goes from
      'theory' to 'practice', establishing a clear link between angiogenesis
      development and imaged angiogenesis features. Once the key role of angiogenesis
      in the development of cancer and in particular prostate cancer has been fully
      described, attention is turned to the current imaging methods with the potential
      to assess the angiogenesis process and, as a consequence, to detect and localise
      prostate cancer. * As confirmed by all available statistics, cancer represents a
      major clinical and societal problem in the developed world. The form of cancer
      with the highest incidence in men is prostate cancer. For prostate cancer, as
      well as for most forms of cancer, detection of the disease at an early stage is
      critical to reduce mortality and morbidity. * Today, it is well known that
      pathological angiogenesis represents a crucial step in cancer development and
      progression. Comparable with most forms of cancer, angiogenesis also plays a
      fundamental role for prostate cancer growth. * As a consequence, angiogenesis is
      an ideal target not only for novel anti-angiogenic therapies, but also for modern
      imaging techniques that aim at cancer localisation by detection of angiogenic
      microvascular changes. * These techniques are mainly based on magnetic resonance,
      ultrasound, and nuclear imaging. * This paper provides a comprehensive review of
      the available studies on angiogenesis in prostate cancer and its use by modern
      and emerging imaging techniques for prostate cancer localisation.

PMID- 22958525
TI  - Dietary sources of energy and macronutrient intakes among Flemish preschoolers.
AB  - This study aims to identify major food sources of energy and macronutrients
      among Flemish preschoolers as a basis for evaluating dietary guidelines. Three
      day estimated diet records were collected from a representative sample of 696
      Flemish preschoolers (2.5-6.5 years old; participation response rate: 50%). For
      11 dietary constituents, the contribution of 57 food groups was computed by
      summing the amount provided by the food group for all individuals divided by the
      total intake of the respective nutrient for all individuals. Bread (12%), sweet
      snacks (12%), milk (6%), flavoured milk drinks (9%), and meat products (6%) were
      the top five energy contributors. Sweet snacks were among the top contributors to
      energy, total fat, all fatty acids, cholesterol, and complex and simple
      carbohydrates. Fruit juices and flavoured milk drinks are the main contributors
      to simple carbohydrates (respectively 14% and 18%). All principal food groups
      like water, bread and cereals, vegetables, fruit, milk and spreadable fats were
      under-consumed by more than 30% of the population, while the food groups that
      were over-consumed consisted only of low nutritious and high energy dense foods
      (sweet snacks, sugared drinks, fried potatoes, sauces and sweet spreads). From
      the major food sources and gaps in nutrient and food intakes, some
      recommendations to pursue the nutritional goals could be drawn: the intake of
      sweet snacks and sugar-rich drinks (incl. fruit juices) should be discouraged,
      while consumption of fruits, vegetables, water, bread and margarine on bread
      should be encouraged.

PMID- 22958526
TI  - Heterologous gene expression in filamentous fungi.
AB  - Filamentous fungi are critical to production of many commercial enzymes and
      organic compounds. Fungal-based systems have several advantages over bacterial
      based systems for protein production because high-level secretion of enzymes is a
      common trait of their decomposer lifestyle. Furthermore, in the large-scale
      production of recombinant proteins of eukaryotic origin, the filamentous fungi
      become the vehicle of choice due to critical processes shared in gene expression
      with other eukaryotic organisms. The complexity and relative dearth of
      understanding of the physiology of filamentous fungi, compared to bacteria, have
      hindered rapid development of these organisms as highly efficient factories for
      the production of heterologous proteins. In this review, we highlight several of
      the known benefits and challenges in using filamentous fungi (particularly
      Aspergillus spp., Trichoderma reesei, and Neurospora crassa) for the production
      of proteins, especially heterologous, nonfungal enzymes. We review various
      techniques commonly employed in recombinant protein production in the filamentous
      fungi, including transformation methods, selection of gene regulatory elements
      such as promoters, protein secretion factors such as the signal peptide, and
      optimization of coding sequence. We provide insights into current models of host
      genomic defenses such as repeat-induced point mutation and quelling. Furthermore,
      we examine the regulatory effects of transcript sequences, including introns and
      untranslated regions, pre-mRNA (messenger RNA) processing, transcript transport,
      and mRNA stability. We anticipate that this review will become a resource for
      researchers who aim at advancing the use of these fascinating organisms as
      protein production factories, for both academic and industrial purposes, and also
      for scientists with general interest in the biology of the filamentous fungi.

PMID- 22958527
TI  - Staphylococcal biofilms: quest for the magic bullet.
AB  - The biofilm phenotype has been recognized only relatively recently in medical
      history but it has rapidly become clear that the development of many, if not the
      majority of bacterial infections depends upon the formation of a biofilm. Medical
      device-related infections are one of the clearest examples of biofilm-dependent
      infections. Bacteria proficiently adhere to and establish biofilms on synthetic
      surfaces, and to date, no material has proven to completely preclude bacterial
      adherence. Any inserted device can be colonized but intravenous catheters, due to
      their widespread use, are the most commonly colonized devices. As many as half a
      million catheter-related infections occur each year in the United States and the
      staphylococci, in particular, Staphylococcus aureus and Staphylococcus
      epidermidis, are the leading cause. Biofilms exhibit tolerance to biocides,
      chemotherapeutic agents, and host-immune defenses and subsequently, biofilm
      associated infections are extremely difficult to treat, frequently chronic, and
      often recurrent, making them a confounding clinical problem. Development of an
      effective strategy for preventing and/or treating these infections is of
      paramount importance and consequently, the search for novel approaches to target
      the biofilm phenotype has exploded in recent years. Because the biofilm phenotype
      is complex, targets for antibiofilm approaches are numerous and this line of
      research is significantly expanding our knowledge about the biofilm mode of
      growth and its role in disease. This review highlights a number of antibiofilm
      approaches that are currently under investigation as novel interventions for
      staphylococcal infections.

PMID- 22958528
TI  - Climate Change and Defense against Pathogens in Plants.
AB  - Most reviews of climate change are epidemiological, focusing on impact assessment
      and risk mapping. However, there are many reports of the effects of environmental
      stress factors on defense mechanisms in plants against pathogens. We review those
      representative of key climate change-related stresses to determine whether there
      are any patterns or trends in adaptation responses. We recognize the complexity
      of climate change itself and the multitrophic nature of the complex biological
      interactions of plants, microbes, soil, and the environment and, therefore, the
      difficulty of reductionist dissection approaches to resolving the problems. We
      review host defense genes, germplasm, and environmental interactions in different
      types of organisms but find no significant group-specific trends. Similarly, we
      review by host defense mechanism type and by host-pathogen trophic relationship
      but identify no dominating mechanism for stress response. However, we do identify
      core stress response mechanisms playing key roles in multiple response pathways
      whether to biotic or abiotic stress. We suggest that these should be central to
      mechanistic climate change plant defense research. We also recognize
      biodiversity, heterogeneity, and the need for understanding stress in a true
      systems biology approach as being essential components of progressing our
      understanding of and response to climate change.

PMID- 22958529
TI  - Advances in the in-field detection of microorganisms in ice.
AB  - The historic view of ice-bound ecosystems has been one of a predominantly
      lifeless environment, where microorganisms certainly exist but are assumed to be
      either completely inactive or in a state of long-term dormancy. However, this
      standpoint has been progressively overturned in the past 20years as studies have
      started to reveal the importance of microbial life in the functioning of these
      environments. Our present knowledge of the distribution, taxonomy, and metabolic
      activity of such microbial life has been derived primarily from laboratory-based
      analyses of collected field samples. To date, only a restricted range of life
      detection and characterization techniques have been applied in the field.
      Specific examples include direct observation and DNA-based techniques
      (microscopy, specific stains, and community profiling based on PCR
      amplification), the detection of biomarkers (such as adenosine triphosphate), and
      measurements of metabolism [through the uptake and incorporation of radiolabeled
      isotopes or chemical alteration of fluorescent substrates (umbelliferones are
      also useful here)]. On-going improvements in technology mean that smaller and
      more robust life detection and characterization systems are continually being
      designed, manufactured, and adapted for in-field use. Adapting technology
      designed for other applications is the main source of new methodology, and the
      range of techniques is currently increasing rapidly. Here we review the current
      use of technology and techniques to detect and characterize microbial life within
      icy environments and specifically its deployment to in-field situations. We
      discuss the necessary considerations, limitations, and adaptations, review
      emerging technologies, and highlight the future potential. Successful application
      of these new techniques to in-field studies will certainly generate new insights
      into the way ice bound ecosystems function.

PMID- 22958530
TI  - Microsatellites for microbiologists.
AB  - Microsatellites are repeating sequences of 2-6base pairs of DNA. Currently, they
      are used as molecular markers in many organisms, specifically in genetic studies
      analyzing kinship and population structure. In addition, they can be used to
      study gene duplication and/or deletion. Although they are used in studies on
      microorganisms including fungi, bacteria, protists, and archaea, it appears that
      these genetic markers are not being utilized to their full microbiological
      potential. Microsatellites have many advantages over other genetic markers
      currently in use as they are in general species specific, and therefore, cross
      contamination by nontarget organisms is rare. Furthermore, microsatellites are
      suitable for use with fast and cheap DNA extraction methods, with ancient DNA or
      DNA from hair and fecal samples used in noninvasive sampling, making them widely
      available as a genetic marker. Microsatellites have already proven to be a useful
      tool for evolutionary studies of pathogenic microorganisms such as Candida
      albicans and Helicobacter pylori, and the onset of new sequencing techniques
      (such as 454, PACBIO, and mini-ion sequencing) means the ability to detect such
      markers will become less time consuming and cheaper, thus further expanding their
      potential to answer important microbial ecology questions.

PMID- 22958531
TI  - Modern Advances against Plague.
AB  - Plague has been a scourge of humanity, responsible for the deaths of millions.
      The etiological agent, Yersinia pestis, has evolved relatively recently from an
      enteropathogen, Yersinia pseudotuberculosis. The evolution of the plague pathogen
      has involved a complex series of genetic acquisitions, deletions, and
      rearrangements in its transition from an enteric niche to becoming a systemic,
      flea-vectored pathogen. With the advent of modern molecular biology techniques,
      we are starting to understand how the organism adapts to the diverse niches it
      encounters and how to combat the threat it poses.

PMID- 22958532
TI  - Salmonella enteritidis in shell eggs: evolving concerns and innovative control
      measures.
AB  - The issue of egg contamination with Salmonella enterica serovar Enteritidis rose
      to prominence several decades ago with increasing rate of infection around the
      world. Recent outbreaks have assured that this problem maintains a place in the
      public consciousness. Extensive research has been conducted to investigate the
      factors precipitating contamination events, their avoidance, and mitigation of
      the threat of contaminated eggs; consequently, regulations have been put in place
      to increase the safety of shell eggs. Despite these measures, rate of illness
      remains significantly higher than projected goals. This chapter includes
      information regarding the contraction of Salmonella species by laying hens and
      the subsequent deposition of these cells in shell eggs. Particular attention will
      be given to the prevalence of Salmonella Enteritidis in eggs and egg-containing
      products relative to other salmonellae. Research has been conducted to elucidate
      the mechanisms behind the fitness of Salmonella Enteritidis strains for this
      environment, but a consensus has yet to be reached. Novel methods of sanitizing
      shell eggs also are reviewed.

PMID- 22958534
TI  - Is exercise training beneficial for heart failure patients taking beta-adrenergic
      blockers? A systematic review and meta-analysis.
AB  - The authors sought to conduct a systematic review comparing the effects of
      exercise training in heart failure patients taking beta-blockers vs those not. A
      systematic search of exercise training trials in chronic heart failure patients
      that compared groups who took beta-blocker medication or compared selective and
      nonselective beta-blockers during exercise training was conducted. Eight
      prospective studies met the criteria for the quantitative synthesis, which
      included data from 236 participants. The increment in peak oxygen consumption
      (VO(2)) was greater in exercising vs control participants, with a mean difference
      (MD) of 1.27 mL/kg/min (95% confidence interval [CI], 0.85-1.70; P<.00001). In
      exercising patients, the increment in peak VO(2) was greater in the group taking
      beta-blocker vs those taking placebo (MD, 1.66 mL/kg/min; 95% CI, 0.36-2.97;
      P=.01). In exercising patients, there was no difference in the increment of peak
      VO(2) between nonselective beta-blocker and selective beta-blockers groups (MD, 
      0.09 mL/kg/min; 95% CI, -1.54-1.36; P=.09). Minnesota Quality of Life Score was
      significantly better in the exercise group vs sedentary control group (both
      groups taking beta-blockers) (MD, -11.3; 95% CI, -15.9 to -6.8; P<.00001). Our
      analysis demonstrated that beta-adrenergic blocker therapy did not reduce
      exercise capacity or exercise training adaptations and quality of life in heart
      failure patients.

PMID- 22958533
TI  - Response of neural reward regions to food cues in autism spectrum disorders.
AB  - BACKGROUND: One hypothesis for the social deficits that characterize autism
      spectrum disorders (ASD) is diminished neural reward response to social
      interaction and attachment. Prior research using established monetary reward
      paradigms as a test of non-social reward to compare with social reward may
      involve confounds in the ability of individuals with ASD to utilize symbolic
      representation of money and the abstraction required to interpret monetary gains.
      Thus, a useful addition to our understanding of neural reward circuitry in ASD
      includes a characterization of the neural response to primary rewards. METHOD: We
      asked 17 children with ASD and 18 children without ASD to abstain from eating for
      at least four hours before an MRI scan in which they viewed images of high
      calorie foods. We assessed the neural reward network for increases in the blood
      oxygenation level dependent (BOLD) signal in response to the food images RESULTS:
      We found very similar patterns of increased BOLD signal to these images in the
      two groups; both groups showed increased BOLD signal in the bilateral amygdala,
      as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct
      group comparisons revealed that the ASD group showed a stronger response to food
      cues in bilateral insula along the anterior-posterior gradient and in the
      anterior cingulate cortex than the control group, whereas there were no neural
      reward regions that showed higher activation for controls than for ASD.
      CONCLUSION: These results suggest that neural response to primary rewards is not
      diminished but in fact shows an aberrant enhancement in children with ASD.

PMID- 22958535
TI  - Evaluation of Thrombi-Stat MC1 for whole blood and plasma international
      normalized ratio in comparison with a laboratory method.
AB  - INTRODUCTION: The precision and comparability of the international normalized
      ratio (INR) analyzed by the Thrombi-Stat MC1 coagulation testing system were
      evaluated before using as a point-of-care testing. METHODS: Three levels of
      control materials were used for within-run and between-run precision study.
      Comparison study of INR determination from citrated whole blood (INR-WB) and
      citrated plasma (INR-PL) analyzed by the Thrombi-Stat MC1 with those by the
      validated method, Sysmex(r) CS-2100i (INR-CS), was performed. RESULTS: The within
      run coefficient of variations (CVs) of INR by the Thrombi-Stat MC1 were 3.60% to
      4.80%. For between-run precision, the CVs were 4.26 to 4.93%. Fifty-four plasmas
      from patients receiving warfarin were included for comparability testing. There
      were good correlation and agreement between both INR-WB and INR-PL compared with
      INR-CS. Eighty-seven percent of INR-WB and 100% of INR-PL were within +/- 0.5
      units of the INR-CS. Given that the therapeutic range was INR-CS of 2-3, 3.7% of
      INR-WB and 5.56% of INR-PL were discordant with the INR-CS. CONCLUSION: The
      precision and comparability to validated method of the Thrombi-Stat MC1 were
      acceptable. Either citrated whole blood or plasma may be used as samples in this
      system. Impact on the management of patients must be taken into consideration
      prior to the implementation of this system.

PMID- 22958536
TI  - Continuous infusion of meropenem in critically ill patients: practical
      considerations.

PMID- 22958537
TI  - Chronic pulmonary aspergilloses: do they exist?

PMID- 22958538
TI  - Six minute walking distance in kyphoscoliosis patients with chronic respiratory
      failure.
AB  - AIM: To evaluate kyphoscoliosis patients with chronic hypercapnic respiratory
      failure (CHRF) using the six minute walk test (6MWT) distance (6MWD) and cardio
      pulmonary function tests. METHOD: This prospective cross-sectional study was
      carried out in a tertiary training and research hospital in Turkey.
      Kyphoscoliosis patients with CHRF on home mechanical ventilation (HMV) followed
      in a respiratory intensive care unit (RICU) out-patient clinic were enrolled.
      Patients' demographics were recorded as well as transthoracic echocardiography
      (ECHO), 6MWD, spirometry, arterial blood gas (ABG) values and high resolution
      chest computed tomography. 6MWT results were compared with other parameters.
      RESULTS: Thirty four patients with kyphoscoliosis and chronic respiratory
      insufficiency admitted to our outpatient clinic were included in the study but 25
      (17 M) patients underwent 6MWT (8 patients walked with oxygen supplement due to
      PaO2 < 60 mm Hg). The mean 6MWD was 274.4 +/- 76.2 (median 270) m and median 6MWD
      predicted rate was 43.7% (inter quartile ratio, IQR, 37.6% to 47.7%). Median HMV
      use was 3 years (IQR 2-4). 6MWD predicted rate, body mass index (BMI), HMV
      duration were similar in male and female patients. 6MWD correlated well with age,
      BMI, dyspnea score for baseline 6MWT (r: - 0.59, p < 0.002, r: - 0.58, p < 0.003,
      r: - 0.55, p < 0.005 respectively) but modestly with forced expiratory volume in
      one second, pulse rate for baseline 6MWT, pulse saturation rate, fatigue and
      dyspnea score at end of 6MWT (r: - 0.44, p < 0.048; r: 0.44, p < 0.027; r: -
      0.43, p < 0.031; r: - 0.42, p < 0.036; r: - 0.42, p < 0.034 respectively). 6MWD
      predicted rate was only correlated with dyspnea score at baseline (r: - 0.46, p <
      0.022). The systolic pulmonary arterial pressure (PAPs) in 6 (24%) cases was more
      than 40 mmHg, in whom mean PaO2/FiO2 was 301.4 +/- 55.4 compared to 280.9 +/-
      50.2 in those with normal PAPs (p > 0.40). CONCLUSION: The 6MWT is an easy way to
      evaluate physical performance limitation in kyphoscoliosis patients with chronic
      hypercapnic respiratory failure using home mechanical ventilation. Nearly 275 m
      was the mean distance walked in the 6MWT, but rather than distance in meters, the
      6MWD predicted rate according to gender and body mass index equation might be a
      better way for deciding about physical performance of these patients. Dyspnea
      score at baseline before the 6MWT may be the most important point that affects
      6MWD in this patient population.

PMID- 22958539
TI  - Sub-optimal delivery of intermittent preventive treatment for malaria in
      pregnancy in Nigeria: influence of provider factors.
AB  - BACKGROUND: The level of access to intermittent preventive treatment for malaria
      in pregnancy (IPTp) in Nigeria is still low despite relatively high antenatal
      care coverage in the study area. This paper presents information on provider
      factors that affect the delivery of IPTp in Nigeria. METHODS: Data were collected
      from heads of maternal health units of 28 public and six private health
      facilities offering antenatal care (ANC) services in two districts in Enugu
      State, south-east Nigeria. Provider knowledge of guidelines for IPTp was assessed
      with regard to four components: the drug used for IPTp, time of first dose
      administration, of second dose administration, and the strategy for sulphadoxine
      pyrimethamine (SP) administration (directly observed treatment, DOT). Provider
      practices regarding IPTp and facility-related factors that may explain
      observations such as availability of SP and water were also examined. RESULTS:
      Only five (14.7%) of all 34 providers had correct knowledge of all four
      recommendations for provision of IPTp. None of them was a private provider. DOT
      strategy was practiced in only one and six private and public providers
      respectively. Overall, 22 providers supplied women with SP in the facility and
      women were allowed to take it at home. The most common reason for doing so
      amongst public providers was that women were required to come for antenatal care
      on empty stomachs to enhance the validity of manual fundal height estimation. Two
      private providers did not think it was necessary to use the DOT strategy because
      they assumed that women would take their drugs at home. Availability of SP and
      water in the facility, and concerns about side effects were not considered
      impediments to delivery of IPTp. CONCLUSION: There was low level of knowledge of
      the guidelines for implementation of IPTp by all providers, especially those in
      the private sector. This had negative effects such as non-practice of DOT
      strategy by most of the providers, which can lead to low levels of adherence to
      IPTp and ineffectiveness of IPTp. Capacity development and regular supportive
      supervisory visits by programme managers could help improve the provision of
      IPTp.

PMID- 22958540
TI  - Analysis of two cases with bronchopulmonary neurofibromatosis.
AB  - Neurogenic tumor of lung is very rare. Only few cases have been reported in the
      literature. We present here two cases of bronchopulmonary neurofibromatosis in
      two adults. In both cases, attempts at imaging failed to diagnose the case, and
      it was the histological study that ensured the diagnosis of neurofibromatosis.
      Biopsy specimens showed bundles of spindle-shaped cells mixed with collagen, and
      on immunohistochemistry some cells were positive for S-100 protein.

PMID- 22958542
TI  - WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.
AB  - SUMMARY: Resistance to antibiotics has increased recently to a dramatic extend,
      and the pipeline of new antibiotics is almost dry for the five next years.
      Failures happen already for trivial community acquired infections, like
      pyelonephritis, or peritonitis, and this is likely to increase. Difficult
      surgical procedures, transplants, and other immunosuppressive therapies will
      become far more risky. Resistance is mainly due to an excessive usage of
      antibiotics, in all sectors, including the animal one. Action is urgently needed.
      Therefore, an alliance against MDRO has been recently created, which includes
      health care professionals, consumers, health managers, and politicians. The
      document highlights the different proposed measures, and represents a strong
      consensus between the different professionals, including general practicionners,
      and veterinarians.

PMID- 22958541
TI  - Nurse led versus lay educators support for those with asthma in primary care: a
      costing study.
AB  - BACKGROUND: Regular review and support for asthma self-management is promoted in
      guidelines. A randomised controlled trial suggested that unscheduled health care
      usage was similar when patients were offered self management support by a lay
      trainer or practice nurses. METHODS: Following the RCT, a costing study was
      undertaken using the trial data to account for the cost of delivery of the
      service under both strategies and the resulting impact on unscheduled healthcare
      (measure of effectiveness) in this trial. RESULTS: One year data (n = 418) showed
      that 29% (61/205) of the nurse group required unscheduled healthcare (177 events)
      compared with 30.5% (65/213) for lay-trainers (178 events).The training costs for
      the lay-trainers were greater than nurses (L36 versus L18 respectively per
      patient, p<0.001), however, the consultation cost for lay-trainers were lower
      than nurses (L6 per patient versus L24, p<0.001). If the cost of unscheduled
      healthcare are accounted for then the costs of nurses is L161, and L135 for lay
      trainers (mean difference L25, [95% CI = -L97, L149, p = 0.681]). The total costs
      (delivery and unscheduled healthcare) were L202 per patient for nurses versus
      L178 for lay-trainers, (mean difference L24, [95%CI = -L100, L147, p = 0.707]).
      CONCLUSIONS: There were no significant differences in the cost of training and
      healthcare delivery between nurse and lay trainers, and no significant difference
      in the cost of unscheduled health care use.

PMID- 22958543
TI  - An exploratory clinical study on the safety and efficacy of an autologous
      fibroblast-seeded artificial skin cultured with animal product-free medium in
      patients with diabetic foot ulcers.
AB  - Cultured dermal substitutes have been used for the treatment of chronic skin
      ulcers; however, the biological risks of animal-derived materials in the culture
      process such as foetal bovine serum (FBS) have been reported. In this study, we
      prepared an autologous fibroblast-seeded artificial dermis (AFD) using animal
      product-free medium supplemented with 2% patient autologous serum and without any
      animal-derived materials such as trypsin in the culturing process. We applied the
      AFD in five patients with diabetic ulcers and investigated its safety and
      efficacy. As the primary endpoint, we defined 'wound bed improvement' according
      to the percentage of granulation area to the whole wound area on day 21, and 60%
      or higher was regarded as improved. The mean age of the patients was 60.6 years
      and the mean duration of the ulcer was 22.6 months. In the evaluation of the
      primary endpoint, the 'wound bed' was improved in all patients [proportion of
      improvement: 100%, 95% confidence interval (CI): 48% to 100%]. Three patients had
      complete wound healing within 12 weeks after application and two patients had
      >80% wound healing at 12 weeks. Side effects were not serious. Our AFD may be a
      safe and effective treatment of diabetic ulcers. 

PMID- 22958544
TI  - Sharing knowledge to advance healthcare policies in Europe for people living with
      dementia and their carers: the ALCOVE project.
AB  - BACKGROUND: Alzheimer's disease and other related dementias are public health
      priorities in the European Union due to their prevalence, cost and profound
      impact on society. Because of these pressing implications, the European Union
      decided to create a Joint Action to share knowledge about dementia and health
      policy in order to preserve the health, quality of life, autonomy and dignity of
      people living with dementia and their carers in Europe. METHODS: ALCOVE is a
      European Community-funded Joint Action coordinated by the HAS (French National
      Authority for Health) with a 24-month duration. The project's life cycle has been
      divided into the following four steps: (1) collection of existing information,
      (2) analysis of existing information and making comparisons across Member States,
      (3) identifying Evidence, Needs, and Priorities, (4) drafting recommendations and
      disseminating them. RESULTS: 19 countries are participating in the ALCOVE
      initiative. The project will publish its final findings in 2013. The project's
      objectives, participants, method, on-going procedures and work plans are already
      available on the ALCOVE website: http://www.alcove-project.eu/. Preliminary
      results show that recommendations will need to focus on clinical and
      epidemiological data collection, diagnostic system assessment, outstanding
      approaches for treating behavioural disorders, limiting antipsychotic use, and
      competence assessment in this vulnerable population. CONCLUSIONS: The European
      Member States involved are mobilized to share best health policy practices in
      order to tackle the challenge of dementia's threat on European health and social
      systems and to improve the quality of life and care for individuals and their
      family carers.

PMID- 22958545
TI  - Adults with autism spectrum disorders exhibit decreased sensitivity to reward
      parameters when making effort-based decisions.
AB  - BACKGROUND: Efficient effort expenditure to obtain rewards is critical for
      optimal goal-directed behavior and learning. Clinical observation suggests that
      individuals with autism spectrum disorders (ASD) may show dysregulated reward
      based effort expenditure, but no behavioral study to date has assessed effort
      based decision-making in ASD. METHODS: The current study compared a group of
      adults with ASD to a group of typically developing adults on the Effort
      Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based
      decision-making. In this task, participants were provided with the probability of
      receiving a monetary reward on a particular trial and asked to choose between
      either an "easy task" (less motoric effort) for a small, stable reward or a "hard
      task" (greater motoric effort) for a variable but consistently larger reward.
      RESULTS: Participants with ASD chose the hard task more frequently than did the
      control group, yet were less influenced by differences in reward value and
      probability than the control group. Additionally, effort-based decision-making
      was related to repetitive behavior symptoms across both groups. CONCLUSIONS:
      These results suggest that individuals with ASD may be more willing to expend
      effort to obtain a monetary reward regardless of the reward contingencies. More
      broadly, results suggest that behavioral choices may be less influenced by
      information about reward contingencies in individuals with ASD. This atypical
      pattern of effort-based decision-making may be relevant for understanding the
      heightened reward motivation for circumscribed interests in ASD.

PMID- 22958547
TI  - Foetal haemoglobin and disease severity in sickle cell anaemia patients in
      Kampala, Uganda.
AB  - BACKGROUND: Sickle cell anaemia (SCA) is a major chronic health problem in
      Uganda. In patients with SCA, the level of foetal haemoglobin (HbF) has been
      found to be important in influencing the clinical course of the disease. Thus
      populations with high levels of HbF like those in Saudi Arabia have been
      described as having a milder clinical course with fewer complications as compared
      to populations with lower levels. Disease modifying drugs can increase the Hb F
      levels and modify the presentation of SCA. METHODS: This was a cross sectional
      study in which we determined foetal haemoglobin levels and examined the
      relationship between HbF levels and disease severity in SCA patients in Mulago
      Hospital, Kampala, Uganda. We consecutively enrolled 216 children aged 1 year to
      18 years with SCA attending the Sickle Cell Clinic at Mulago Hospital whose
      guardians had given consent. The history included age at onset of initial
      symptoms and diagnosis, number of hospitalisations and blood transfusions and
      other complications of SCA (cardiovascular accidents, avascular hip necrosis and
      priapism). A detailed physical examination was performed to assess the current
      state and help describe the disease severity for each patient. Blood samples were
      drawn for HbF levels. HbF levels >=10% was defined as high. RESULTS: Of the 216
      children, (80) 37% had HbF levels >=10%. Significant correlations were observed
      between HbF level and several clinical parameters independent of age including
      age at diagnosis (p value 0.013), number of hospitalisations (p value 0.024) and
      transfusions (p value 0.018) since birth. CONCLUSION: A third of the children
      with SCA attending the Sickle cell clinic in Mulago Hospital have high HbF
      levels. Higher HbF level is associated with later onset of symptoms and
      presentation, and less severe disease characterised by fewer hospitalisations and
      blood transfusions. We suggest HbF levels should be determined at initial contact
      for patients with SCA to guide counselling and identify those who may need closer
      follow up and consideration for disease modifying drugs.

PMID- 22958548
TI  - Evaluation of an FFQ to assess total energy and nutrient intakes in severely
      obese pregnant women.
AB  - OBJECTIVE: FFQ are popular instruments for assessing dietary intakes in
      epidemiological studies but have not been validated for use in severely obese
      pregnancy. The aim of the present study was to compare nutrient intakes assessed
      by an FFQ with those obtained from a food diary among severely obese pregnant
      women. DESIGN: Comparison of an FFQ containing 170 food items and a food diary
      for 4 d (three weekdays and one weekend day); absolute agreement was assessed
      using the paired t test and relative agreement by Pearson/Spearman correlation,
      crossclassification into tertiles and weighted kappa values. SETTING: Antenatal
      metabolic clinic for severely obese women. SUBJECTS: Thirty-one severely obese
      (BMI at booking >= 40.0 kg/m2) and thirty-two lean control (BMI520.0-24.9 kg/m2)
      pregnant women. RESULTS: The findings showed that nutrient intakes estimated by
      the FFQ were significantly higher than those from the food diary; average
      correlation was 0.32 in obese and 0.43 in lean women. A mean of 48.5% of obese
      and 47.3% of lean women were correctly classified, while 12.9% (obese) and 10.0%
      (lean) were grossly misclassified. Weighted k values ranged from 20.04 to 0.79 in
      obese women and from 0.16 to 0.78 in lean women. CONCLUSIONS: Overall, the
      relative agreement between the FFQ and food diary was lower in the obese group
      than in the lean group, but was comparable with earlier studies conducted in
      pregnant women. The validity assessments suggest that the FFQ is a useful tool
      for ranking severely obese pregnant women according to the levels of their
      dietary intake.

PMID- 22958549
TI  - A crisis resolution and home treatment team in Norway: a longitudinal survey
      study Part 2. Provision of professional services.
AB  - BACKGROUND: Crisis resolution and home treatment (CRHT) is an emerging mode of
      delivering acute mental health care in the community. There is a paucity of
      knowledge regarding the workings of CRHT in the literature. This is the second
      paper in a series of three from the longitudinal survey of patients of a CRHT
      team in Norway, which was aimed at describing the characteristics of patients
      served, professional services provided, and clinical outcomes. This report
      focuses on the provision of professional services by the team. METHODS: The
      project was a descriptive, quantitative study based on the patient data from a
      longitudinal survey of one CRHT team in Norway. The participants of the survey, a
      total of 363 patients, constituted the complete registration of patients of this
      team in the period from February 2008 to July 2009. RESULTS: The average length
      of service by the team was about 15 days, and those with depression as the major
      symptom had the longest mean length of stay on the team. The team was engaged in
      providing a variety of services including individual treatments involving
      multiple professionals, group treatment meetings, and coordination activities
      involving external service sectors. While the type of professionals providing
      individual treatment was not associated with the severity level of clinical
      problems, those receiving various group treatment meetings had more serious level
      of clinical symptoms than those not receiving group treatment meetings. In
      addition coordination activities involving healthcare professionals and social
      services in the community were in line with the patients' clinical and social
      needs. The results of the study show that the team functioned effectively in
      addressing the general guidelines for the functioning of CRHT teams.

PMID- 22958546
TI  - Epidemiology of chicken anemia virus in Central African Republic and Cameroon.
AB  - BACKGROUND: Although chicken anemia virus (CAV) has been detected on all
      continents, little is known about this virus in sub-Saharan Africa. This study
      aimed to detect and characterize CAV for the first time in Central African
      Republic and in Cameroon. RESULTS: An overall flock seroprevalence of 36.7% was
      found in Central African Republic during the 2008-2010 period. Virus prevalences
      were 34.2% (2008), 14.3% (2009) and 10.4% (2010) in Central African Republic and
      39% (2007) and 34.9% (2009) in Cameroon. CAV DNA was found in cloacal swabs of
      76.9% of seropositive chickens, suggesting that these animals excreted the virus
      despite antibodies. On the basis of VP1 sequences, most of the strains in Central
      African Republic and Cameroon belonged to 9 distinct phylogenetic clusters at the
      nucleotide level and were not intermixed with strains from other continent.
      Several cases of mixed infections in flocks and individual chickens were
      identified. CONCLUSIONS: Our results suggest multiple introductions of CAV in
      each country that later spread and diverged locally. Mixed genotype infections
      together with the observation of CAV DNA in cloacal samples despite antibodies
      suggest a suboptimal protection by antibodies or virus persistence.

PMID- 22958550
TI  - Prognostic significance of lymph node yield after long-course preoperative
      radiotherapy in patients with rectal cancer: a systematic review.
AB  - AIM: A literature review was performed to elucidate whether long-course
      preoperative radiotherapy for patients with rectal cancer affects lymph node
      yield, and whether this influences prognosis. METHOD: Cochrane Database,
      PubMed/MEDLINE, Scopus, Web of Knowledge, Embase and CINAHL databases and
      reference lists from published journal articles published between 1 January 1990
      and 30 June 2011 were searched. Studies examining lymph node yield and prognosis
      were selected for review. RESULTS: One thousand and twenty-nine articles were
      found, of which 11 met the inclusion criteria. None was a randomized controlled
      trial and all were cohort studies. Four studies showed that long-course
      preoperative radiotherapy reduced lymph node yield; however only one demonstrated
      a statistically significant survival benefit in patients with higher lymph node
      yields. Five-year survival was 48% in patients with fewer than and 69% in those
      with more than 11 lymph nodes identified in the operative specimen (P = 0.04).
      CONCLUSION: Whilst long-course preoperative radiotherapy appears to reduce lymph
      node yield in patients with rectal cancer, no causal relationship between lymph
      node yield and survival can be established in this group of patients.

PMID- 22958552
TI  - Highlights of the first twenty years of the ERS, 1990-2010 past presidents of the
      ERS recall activities during their term of office.

PMID- 22958551
TI  - In ovo leptin administration affects hepatic lipid metabolism and microRNA
      expression in newly hatched broiler chickens.
AB  - BACKGROUND: A leptin-like immunoreactive substance has been found in chicken eggs
      and has been implicated in serving as a maternal signal to program offspring
      growth and metabolism. In the present study, we investigated the effects of in
      ovo leptin administration on hatch weight, serum and hepatic concentrations of
      metabolites and hormones, as well as on the expression of genes involved in
      hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the
      affected genes. To this end we injected fertile eggs with either 0.5 MUg of
      recombinant murine leptin or vehicle (PBS) before incubation. RESULTS: Prenatally
      leptin-exposed chicks showed lower hatch weight, but higher liver weight relative
      to the body weight, compared to the control group. In ovo leptin treatment
      increased the hepatic content and serum concentration of leptin in newly hatched
      chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch)
      were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB)
      were increased. The hepatic mRNA expression of sterol regulator element binding
      protein 1 (SREBP-1c), SREBP-2, hydroxy-3-methylglutaryl coenzyme A reductase
      (HMGCR) and cholesterol 7alpha-hydroxylase 1 (CYP7A1) was significantly up
      regulated, as was the protein content of both SREBP-1c and SREBP-2 in hepatic
      nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targeting
      SREBP-1c and/or HMGCR, five were significantly up-regulated in liver of leptin
      treated chicks, including gga-miR-200b and gga-miR-429, which target both SREBP
      1c and HMGCR. CONCLUSIONS: These results suggest that leptin in ovo decreases
      hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly
      hatched broiler chickens, possibly via microRNA-mediated gene regulation.

PMID- 22958553
TI  - Psychosocial aspects of anal cancer screening: a review and recommendations.
AB  - Cancer screening programs have the potential to decrease psychosocial wellbeing.
      This review investigates the evidence that anal cancer screening has an impact on
      psychosocial functioning and outlines considerations for supporting participants.
      The review suggested that screening has no significant effect on general mental
      health but may increase cancer-specific worry. Having worse anal or HIV symptoms,
      being younger, higher baseline distress or worse histology results were
      predictive of greater worry. The findings suggest the need to increase education
      campaigns, particularly targeting those with HIV infection and men who have sex
      with men. There is a need to develop a consensus on measuring the psychosocial
      impact of screening and stepped care approaches for responding to any resulting
      distress.

PMID- 22958554
TI  - Belgian health-related data in three international databases.
AB  - AIMS OF THE STUDY: This study wants to examine the availability of Belgian
      healthcare data in the three main international health databases: the World
      Health Organization European Health for All Database (WHO-HFA), the Organisation
      for Economic Co-operation and Development Health Data 2009 and EUROSTAT. METHODS:
      For the indicators present in the three databases, the availability of Belgian
      data and the source of these data were checked. MAIN FINDINGS: The most important
      problem concerning the availability of Belgian health-related data in the three
      major international databases is the lack of recent data. Recent data are
      available for 27% of the indicators of the WHO-HFA database, 73% of the OECD
      Health Data, and for half of the Eurostat indicators. Especially recent data
      about health status (including mortality-based indicators) are lacking.
      DISCUSSION: Only the availability of the health-related data is studied in this
      article. The quality of the Belgian data is however also important to examine.The
      main problem concerning the availability of health data is the timeliness. One of
      the causes of this lack of (especially mortality) data is the reform of the
      Belgian State. Nowadays mortality data are provided by the communities. This
      results in a delay in the delivery of national mortality data. However several
      efforts are made to catch up.

PMID- 22958555
TI  - The history of lower back pain: a look "back" through the centuries.
AB  - The diagnosis and treatment of low back pain must be standardized, based on
      evidence and solid research. The cost to individuals and society is great and
      only those diagnostic tests or treatments that can improve the quality and cost
      of care should be advocated.

PMID- 22958556
TI  - Evaluation and diagnosis of low back pain.
AB  - The diagnosis of low back pain is complicated by the varying presentations and
      complex nature of pain and the nonstandardized approach by physicians to clinical
      decision making. Only a few physicians use evidence-based guidelines to assist
      with clinical decision making. This article reviews a systematic approach to the
      evaluation and diagnosis of low back pain.

PMID- 22958557
TI  - Treatment: current treatment recommendations for acute and chronic
      undifferentiated low back pain.
AB  - This article is an overview of current treatment recommendations for low back
      pain, and includes recommendations from the Joint Clinical Practice Guideline
      from the American College of Physicians and the American Pain Society. An
      algorithm is offered as well as a review of the new recommendations for
      diagnosis, evaluation, and treatment of low back pain.

PMID- 22958558
TI  - The physiology of low back pain.
AB  - Pain by definition is subjective. A variety of neural pathways are involved in
      the generation and propagation of pain. Pain is emotional. Pain pathways interact
      with the limbic system, and this interaction modulates pain. The experience of
      pain is related to the experience of past pain. Many potential pain generators
      are present in the low back. The most likely source of pain is the intervertebral
      disc. Treating pain requires a multifactorial approach, because pain is very
      complex.

PMID- 22958559
TI  - Low back pain: pharmacologic management.
AB  - Adequate treatment of low back pain is essential, but has been challenging for
      many primary care physicians. Most patients with low back pain can be treated in
      the primary care environment, provided the physician has enough knowledge of the
      medications used to treat low back pain. The main treatment goal for acute low
      back pain is to control the pain and maintain function. For patients with chronic
      back pain, the goal is continual pain management and prevention of future
      exacerbations. This article reviews current pharmacological options for the
      treatment of low back pain, and possible future innovations.

PMID- 22958560
TI  - Mechanical therapy for low back pain.
AB  - Physical therapy and manual medicine for low back pain encompass many different
      treatment modalities. There is a vast variety of techniques that physical
      therapists commonly use in the treatment of low back pain. Some of the therapies
      include, but are certainly not limited to, education, exercise, lumbar traction,
      manual manipulation, application of heat, cryotherapy, and ultrasonography. Many
      of these approaches are discussed specifically in this article.

PMID- 22958561
TI  - Nonsurgical interventions for low back pain.
AB  - A variety of nonoperative interventions are available to treat back pain. Careful
      assessment, discussion, and planning need to be performed to individualize care
      to each patient. This article discusses good to fair evidence from randomized
      controlled trials that injection therapy, percutaneous intradiscal radiofrequency
      thermocoagulation, intradiscal electrothermal therapy, and prolotherapy are not
      effective. Evidence is poor from randomized controlled trials regarding local
      injections, Botox, and coblation nucleoplasty; however, with a focused approach,
      the right treatment can be provided for the right patient. To be more effective
      in management of back pain, further high-grade randomized controlled trials on
      efficacy and safety are needed.

PMID- 22958562
TI  - Surgical treatment of low back pain.
AB  - There is a need for quality trials that study optimal selection and timing of
      surgical treatment options. Studies are needed of cost-effectiveness and effect
      on long-term improvement. Until data from such studies are available, primary
      physicians should follow the guidelines on conservative management and
      aggressively evaluate the red flags of low back pain, immediately refer for
      neurologic deficit and bowel or bladder compromise, and focus treatment on
      modalities with high-quality evidence-based information. Patients who do not
      improve can be referred to surgeons with experience and expertise in
      discectomies.

PMID- 22958563
TI  - Complementary and alternative medicine treatments for low back pain.
AB  - Complementary and alternative medicine, often referred to as integrated medicine,
      is often used for the treatment of low back pain. This article presents 6
      therapies (ie, behavioral treatment, acupuncture, manipulation, prolotherapy,
      neuroreflexotherapy, and herbal treatments), which are discussed in terms of the
      specifics of the modality, as well as the empirical evidence related to their
      effectiveness.

PMID- 22958564
TI  - Working with pain clinics and other consultants concerning low back pain.
AB  - Although primary care physicians are able to manage low back pain, often it is
      necessary to refer to other specialists. This article reviews how primary care
      physicians can refer to pain clinics and work with consultants.

PMID- 22958565
TI  - The disability evaluation and low back pain.
AB  - In the United States an estimated 11 million persons are unable to work, with 8.1
      million unable to work to their full capacity. Primary care physicians are often
      called on for the evaluation and determination of patients with claims for
      disability. Knowledge of the system for disability determination and a systematic
      approach facilitates the process. This article focuses on the requirements of the
      Social Security Administration, under federal law tasked to administer the Social
      Security Disability Insurance program and the Supplemental Security Income
      program, and offers an approach to the evaluation of patients with claims of
      disability.

PMID- 22958567
TI  - Medical-legal issues regarding patients with low back pain.
AB  - Low back pain can present legal issues that require input from the patient's
      treating physicians. Because low back pain can lead to partial or complete
      disability, either on a short-term or long-term basis, patients may be unable to
      earn a living, which may make it necessary for patients to seek government aid,
      personal insurance benefits, or insurance benefits through workers compensation
      or even, when the low back pain was caused by an incident that was the fault of a
      third party, through a personal injury claim lawsuit. This article reviews the
      legal issues relevant to low back pain.

PMID- 22958568
TI  - "A pain in the back".

PMID- 22958566
TI  - Pain processing in the human nervous system: a selective review of nociceptive
      and biobehavioral pathways.
AB  - This selective review discusses the psychobiological mediation of nociception and
      pain. Summarizing literature from physiology and neuroscience, first an overview
      of the neuroanatomic and neurochemical systems underpinning pain perception and
      modulation is provided. Second, findings from psychological science are used to
      elucidate cognitive, emotional, and behavioral factors central to the pain
      experience. This review has implications for clinical practice with patients
      suffering from chronic pain, and provides strong rationale for assessing and
      treating pain from a biopsychosocial perspective.

PMID- 22958569
TI  - Lowback pain diagnosis and treatment. Preface.

PMID- 22958570
TI  - GO2PUB: Querying PubMed with semantic expansion of gene ontology terms.
AB  - BACKGROUND: With the development of high throughput methods of gene analyses,
      there is a growing need for mining tools to retrieve relevant articles in PubMed.
      As PubMed grows, literature searches become more complex and time-consuming.
      Automated search tools with good precision and recall are necessary. We developed
      GO2PUB to automatically enrich PubMed queries with gene names, symbols and
      synonyms annotated by a GO term of interest or one of its descendants. RESULTS:
      GO2PUB enriches PubMed queries based on selected GO terms and keywords. It
      processes the result and displays the PMID, title, authors, abstract and
      bibliographic references of the articles. Gene names, symbols and synonyms that
      have been generated as extra keywords from the GO terms are also highlighted.
      GO2PUB is based on a semantic expansion of PubMed queries using the semantic
      inheritance between terms through the GO graph. Two experts manually assessed the
      relevance of GO2PUB, GoPubMed and PubMed on three queries about lipid metabolism.
      Experts' agreement was high (kappa = 0.88). GO2PUB returned 69% of the relevant
      articles, GoPubMed: 40% and PubMed: 29%. GO2PUB and GoPubMed have 17% of their
      results in common, corresponding to 24% of the total number of relevant results.
      70% of the articles returned by more than one tool were relevant. 36% of the
      relevant articles were returned only by GO2PUB, 17% only by GoPubMed and 14% only
      by PubMed. For determining whether these results can be generalized, we generated
      twenty queries based on random GO terms with a granularity similar to those of
      the first three queries and compared the proportions of GO2PUB and GoPubMed
      results. These were respectively of 77% and 40% for the first queries, and of 70%
      and 38% for the random queries. The two experts also assessed the relevance of
      seven of the twenty queries (the three related to lipid metabolism and four
      related to other domains). Expert agreement was high (0.93 and 0.8). GO2PUB and
      GoPubMed performances were similar to those of the first queries. CONCLUSIONS: We
      demonstrated that the use of genes annotated by either GO terms of interest or a
      descendant of these GO terms yields some relevant articles ignored by other
      tools. The comparison of GO2PUB, based on semantic expansion, with GoPubMed,
      based on text mining techniques, showed that both tools are complementary. The
      analysis of the randomly-generated queries suggests that the results obtained
      about lipid metabolism can be generalized to other biological processes. GO2PUB
      is available at http://go2pub.genouest.org.

PMID- 22958571
TI  - Cisplatin and 5-fluorouracil in inoperable, stage IV squamous cell carcinoma of
      the penis.
AB  - What's known on the subject? and What does the study add? Metastatic or locally
      advanced squamous cell carcinoma of the penis (SCCP) is generally incurable, but
      it can be palliated with systemic chemotherapy. Two retrospective studies,
      involving <10 patients each, showed that cisplatin plus continuous infusion of 5
      fluorouracil (5-FU) may be effective and well tolerated. Cisplatin, methotrexate
      and bleomycin, cisplatin and irinotecan and taxanes can also play an important
      role for patients with locally advanced/metastatic SCCP. Finally, anti-EGFR
      therapy may also be effective in advanced SCCP. Although cisplatin plus
      continuous infusion of 5-FU is widely used in clinical practice for palliation of
      SCCP, toxicity and efficacy data regarding this schedule include a total of 14
      patients with SCCP, treated more than two decades ago. In our retrospective
      study, cisplatin plus continuous infusion of 5-FU was used for palliative
      purposes in a homogenous sample of 25 patients with SCCP. Partial responses and
      stable disease were observed in 8 (32%) and 10 (40%) patients, respectively, with
      a median progression-free survival of 20 weeks. Neutropenia was the most
      important grade 3-4 side effect observed, occurring in 20% of patients. These
      data provide confirmation that such a combination regimen is moderately effective
      and well tolerated in patients with SCCP. OBJECTIVE: * To investigate the
      activity and toxicity of 5-fluorouracil (5-FU) as a first-line treatment in
      metastatic squamous cell carcinoma of the penis (SCCP). METHODS: * The medical
      records of 78 patients with SCCP treated between January 2000 and June 2011 at
      the four participating centres were reviewed. * Data regarding patients treated
      with first-line 5-FU were extracted. * Patients were included in the study if
      radiological reports were available for determination of response and progression
      free survival (PFS) according to response evaluation criteria in solid tumours
      (RECIST) 1.1. RESULTS: * Between January 2000 and June 2011, 25 patients were
      treated with i.v. cisplatin on day 1 followed by 5-FU as a continuous 24-h
      infusion for 4 days every 3 weeks until disease progression or unacceptable
      toxicity. Partial responses and stable disease were observed in eight (32%) and
      10 (40%) patients, respectively, with a disease control rate of 72%. * Severe
      neutropenia was the most important grade 3-4 side effect observed, occurring in
      20% of patients. * The median (interquartile range [IQR]) PFS was 20 (11-20)
      weeks and the median (IQR) overall survival (OS) was 8 (7-12) months. CONCLUSION:
      * 5-FU is associated with a moderate response rate and is well tolerated in
      patients with metastatic SCCP.

PMID- 22958572
TI  - New approaches to investigating social gestures in autism spectrum disorder.
AB  - The combination of economic games and human neuroimaging presents the
      possibility of using economic probes to identify biomarkers for quantitative
      features of healthy and diseased cognition. These probes span a range of
      important cognitive functions, but one new use is in the domain of reciprocating
      social exchange with other humans - a capacity perturbed in a number of
      psychopathologies. We summarize the use of a reciprocating exchange game to
      elicit neural and behavioral signatures for subjects diagnosed with autism
      spectrum disorder (ASD). Furthermore, we outline early efforts to capture
      features of social exchange in computational models and use these to identify
      quantitative behavioral differences between subjects with ASD and matched
      controls. Lastly, we summarize a number of subsequent studies inspired by the
      modeling results, which suggest new neural and behavioral signatures that could
      be used to characterize subtle deficits in information processing during
      interactions with other humans.

PMID- 22958574
TI  - Number needed to treat for subglottic secretion drainage technology as a
      ventilator-associated pneumonia prevention strategy.
AB  - The number needed to treat can be calculated for ventilator-associated pneumonia
      reduction strategies such as subglottic secretion drainage technology based on
      previous work establishing its relative risk reduction. Assuming an incidence of
      4%, employing subglottic secretion drainage in 33 patients will prevent one case
      of ventilator-associated pneumonia, and thus potentially 4 cases annually in an
      average hospital in the United States. With a previously described limit of L300
      ($470 USD) additional cost per 10 days of ventilation as a threshold of
      investment for technologies to reduce ventilator-associated pneumonia, subglottic
      secretion drainage technology is both clinically and cost effective. 

PMID- 22958573
TI  - Pseudothrombocytopenia or platelet clumping as a possible cause of low platelet
      count in patients with viral infection: a case series from single institution
      focusing on hepatitis A virus infection.
AB  - INTRODUCTION: Pseudothrombocytopenia (PTCP) is the phenomenon of
      ethylenediaminetetraacetic acid anticoagulant-activated platelet clumping, which
      results in artificially low platelet counts. Other investigators have reported a
      few cases of PTCP associated with viral infections. The objective of this study
      was to demonstrate the association of viral infection with PTCP. METHODS: Medical
      records of patients with thrombocytopenia who were tested for peripheral blood
      smear examination between March 2009 and February 2011 were reviewed for platelet
      clumping and viral infection. RESULTS: Thrombocytopenic patients with viral
      infection had a higher frequency of platelet clumping than those with other
      diseases, which was statistically significant (13.8% vs. 6.5%, respectively: P =
      0.003). Among the 18 cases where PTCP or platelet clumping was related to viral
      infection, hepatitis A virus infection (72.2%) was most common, followed by
      cytomegalovirus (11.1%) and influenza A H1N1 infections (5.6%). A third (33.3%)
      of the patients had platelet counts <100 * 109/L. CONCLUSION:
      Pseudothrombocytopenia or platelet clumping should be considered in patients with
      acute viral infection, particularly if the platelet count is unexpectedly low,
      because failure to recognize PTCP may lead to unnecessary diagnostic tests and
      patient mismanagement.

PMID- 22958575
TI  - Offspring ADHD as a risk factor for parental marital problems: controls for
      genetic and environmental confounds.
AB  - BACKGROUND: Previous studies have found that child attention
      deficit/hyperactivity disorder (ADHD) is associated with more parental marital
      problems. However, the reasons for this association are unclear. The association
      might be due to genetic or environmental confounds that contribute to both
      marital problems and ADHD. METHOD: Data were drawn from the Australian Twin
      Registry, including 1,296 individual twins, their spouses, and offspring. We
      studied adult twins who were discordant for offspring ADHD.Using a discordant
      twin pairs design, we examined the extent to which genetic and environmental
      confounds,as well as measured parental and offspring characteristics, explain the
      ADHD-marital problems association. RESULTS: Offspring ADHD predicted parental
      divorce and marital conflict. The associations were also robust when comparing
      differentially exposed identical twins to control for unmeasured genetic and
      environmental factors, when controlling for measured maternal and paternal
      psychopathology,when restricting the sample based on timing of parental divorce
      and ADHD onset, and when controlling for other forms of offspring
      psychopathology. Each of these controls rules out alternative explanations for
      the association. CONCLUSION: The results of the current study converge with those
      of prior research in suggesting that factors directly associated with offspring
      ADHD increase parental marital problems.

PMID- 22958576
TI  - Prevalence and correlations with depression, anxiety, and other features in
      outpatients with chronic obstructive pulmonary disease in China: a cross
      sectional case control study.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often
      experience depression and anxiety, but little information is available regarding
      Chinese patients with these conditions. The present study assessed depression and
      anxiety in Chinese patients with COPD. METHODS: A case-controlled study was
      designed with 1100 patients with COPD enrolled in the case group and1100
      residents without COPD and respiratory symptoms selected as the control group.
      Anxiety and depression in both groups were evaluated using the Hospital Anxiety
      and Depression Scale (HADS). The body mass index,degree of airflow obstruction,
      dyspnea, and exercise capacity (BODE ) index was used to assess COPD severity.
      Binary logistic regression models were used to test the association between
      anxiety and depression. RESULTS: The patients with COPD were more likely than
      controls to experience depression (cases, HADS 10.5 +/- 3.6, prevalence 35.7%;
      controls, HADS 8.7 +/- 2.7, prevalence 7.2%) and anxiety (cases, HADS 10.4 +/-
      3.1, prevalence 18.3%; controls, HADS 8.6 +/- 2.1, prevalence 5.3%). Subjects
      with anxious and depressive symptoms had poorer health outcomes including a
      higher BODE index, a shorter 6-minute-walk distance (6MWD), more dyspnea, and a
      higher St George's respiratory questionnaire (SGRQ) score. The prevalence of
      anxious and depressive symptoms increased with increasing BODE scores. On the
      basis of binary logistic regression, the BODE index was significantly correlated
      with anxiety (OR = 1.47, p < 0.001) and depression (OR = 1.51, p < 0.001).
      Anxious and depressive symptoms were also associated with several factors
      including younger age, female sex, higher education level, lower household income
      and history of smoking. CONCLUSIONS: This study confirmed the high prevalence of
      anxiety and depression in Chinese outpatients with COPD. Patients with COPD who
      had anxiety and/or depression had a poorer health-related quality of life. TRIAL
      REGISTRATION: Chinese Clinical Trials Registration(ChiCTR-TRC-12001958).

PMID- 22958577
TI  - Cognitive profile in persons with systolic and diastolic heart failure.
AB  - Persons with heart failure (HF) have four times the risk of having cognitive
      impairment compared with the general population and display different patterns of
      cognitive impairment. This secondary analysis of a published cross-sectional
      study of 90 community-dwelling adults examined the Montreal Cognitive Assessment
      (MoCA) scores and HF differentiated as systolic and diastolic HF. Mean MoCA score
      was 22.9 (standard deviation+/-2.31) in persons with systolic HF (n=69) and 24.8
      (standard deviation+/-2.76) in persons with diastolic HF (n=21) with
      statistically significant mean difference between groups (t=-2.025, P=.030).
      Independent t test on the eight MoCA domain scores and systolic and diastolic HF
      indicated significance on visuo-spatial/executive function (P=.026), attention
      (P=.049), abstraction (P=.014), and delayed recall (P=.048). Findings from this
      study support the need for including persons with systolic and diastolic HF in
      future researches on identifying varying cognitive profiles to plan tailored
      cognitive intervention.

PMID- 22958578
TI  - Fee exemption for caesarean section in Morocco.
AB  - Financial barriers are an important obstacle for access to emergency obstetric
      care and a contributing factor to too slow a reduction in the level of maternal
      mortality. In Morocco, in 2009, a fee exemption policy for delivery and caesarean
      section was implemented in public maternity hospitals. As in most countries where
      a fee exemption policy has been implemented, fee exemption is considered synonym
      to free care. However, other direct costs may subsist. The objective of this
      study was to get an estimate of the actual cost of caesarean sections from the
      patients' perspective.This study was carried out in April 2010 in the three
      public hospitals in Fez. We carried out semi-structured interviews among a sample
      of 100 women who gave birth by caesarian section in the public hospitals in Fez.
      The results showed that households paid between US$169 (95% Confidence Interval
      (CI): 153, 185) at the provincial and regional hospitals, and US$291 (95% CI: 224
      359) at the university hospital (UH) where the fee exemption was not applied. The
      direct cost of a caesarean was mainly influenced by the price of the drugs the
      families bought, the invoice paid at UH, and the transport. Finally, although the
      fee exemption policy for caesareans has probably reduced the total cost for
      households who did not have access to a poverty card, it has not led to 'truly'
      free caesarean deliveries.

PMID- 22958579
TI  - Partaking in the global movement for occupational mental health: what challenges
      and ways forward for sub-Sahara Africa?
AB  - There is an ongoing global movement for the entrenchment of occupational mental
      health as an integral part of occupational health and safety schemes. Aside from
      being a fundamental human right issue, this move has been demonstrated to be of
      cost-benefit in terms of workplace productivity and general economic growth.
      Despite being among the regions most prone to the human and economic
      repercussions of work-related mental health problems by reason of her socio
      economic circumstance; sub-Sahara Africa is yet to fully plug into this movement.
      With a view to make recommendations on the ways forward for sub-Sahara Africa,
      this paper examines the current state of and the barriers to effective
      occupational mental health policy and practice in the region.

PMID- 22958580
TI  - A comparison of three induction regimens using succinylcholine, vecuronium, or no
      muscle relaxant: impact on the intraoperative monitoring of the lateral spread
      response in hemifacial spasm surgery: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Surgical microvascular decompression (MVD) is the curative treatment
      for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread
      response (LSR) intraoperatively can predict a successful clinical outcome.
      However, the rate of the LSR varies between trials, and the reason for this
      variation is unclear. The aim of our trial is to evaluate the rate of the LSR
      after intubation following treatment with succinylcholine, vecuronium, or no
      muscle relaxant. METHODS AND DESIGN: This trial is a prospective randomised
      controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD
      under general anaesthesia. Patients are randomised to receive succinylcholine,
      vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be
      recorded until dural opening. The primary outcome of this study is the rate of
      the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal
      symptoms, the rate of difficult intubations, the rate of adverse haemodynamic
      events and the relationship between the measurement of LSR or not, and clinical
      success rates at 30 days after surgery. DISCUSSION: This study aims to evaluate
      the impact of muscle relaxants on the rate of the LSR, and the study may provide
      evidence supporting the use of muscle relaxants before intubation in patients
      with HFS undergoing MVD surgery. TRIALS REGISTRATION: http://www.chictr.org/
      ChiCTR-TRC-11001504 Date of registration: 24 June, 2011. The date the first
      patient was randomised: 30 September, 2011.

PMID- 22958581
TI  - The epidemiology of anal cancer.
AB  - Anal cancer comprises malignancies of the anal canal principally of two
      morphologic variants: squamous cell carcinoma (SCC) and adenocarcinoma. In most
      settings, SCC compromises more than 70% of cases. In the general population, anal
      cancer is uncommon, with age-standardised incidence rates mostly between 1 and 2
      per 100000 per year. However, incidence of anal SCC is increasing by 1-3% per
      year in developed country settings. High-risk human papillomavirus (HPV) types
      can be detected in 80-90% of all anal SCC cases, making it second only to
      cervical cancer in the closeness of its association with this virus. HPV-16 can
      be detected in ~90% of HPV-positive cases of anal SCC. Case-control studies have
      demonstrated that sexual risk factors (homosexuality in men and multiple sexual
      partners in women) are strongly associated with anal cancer risk. Other risk
      factors include immune deficiency and tobacco exposure. Anal cancer rates are
      highest in homosexual men, particularly in those who are HIV-positive, in whom
      anal cancer is among the most common of all cancers. Vaccination against HPV
      holds great promise for anal cancer prevention for those not already HPV
      infected. For the current generation of adult high-risk populations, screening
      programs to allow early detection and treatment are under investigation.

PMID- 22958582
TI  - Asthma in pregnancy - from immunology to clinical management.
AB  - Asthma is one of the most common chronic medical conditions that may complicate
      pregnancy. Asthma influences the outcome of pregnancy and, vice versa, pregnancy
      affects asthma severity, but the underlying immunological mechanisms of this
      interaction are not fully understood. As a sign of pregnancy-induced
      immunotolerance, attenuation of allergic responses can be detected in controlled
      asthmatic pregnant patients; however non controlled asthmatic pregnant women show
      significant asthma-associated immune reactions that may, beside other factors,
      influence fetal growth. Generally, although uncontrolled asthma may increase the
      risk of adverse perinatal outcomes, women with well-controlled and adequately
      treated disease during pregnancy do not develop maternal or fetal complications.

PMID- 22958583
TI  - Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected
      individuals: a nested case-control study.
AB  - BACKGROUND: The delay in initiating treatment for tuberculosis (TB) in HIV
      infected individuals may lead to the development of a more severe form of the
      disease, with higher rates of morbidity, mortality and transmissibility. The aim
      of the present study was to estimate the time interval between the onset of
      symptoms and initiating treatment for TB in HIV-infected individuals, and to
      identify the factors associated to this delay. METHODS: A nested case-control
      study was undertaken within a cohort of HIV-infected individuals, attended at two
      HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating
      treatment for TB was defined as the period of time, in days, which was greater
      than the median value between the onset of cough and initiating treatment for TB.
      The study analyzed biological, clinical, socioeconomic, and lifestyle factors as
      well as those related to HIV and TB infection, potentially associated to delay.
      The odds ratios were estimated with the respective confidence intervals and p
      values. RESULTS: From a cohort of 2365 HIV-infected adults, 274 presented
      pulmonary TB and of these, 242 participated in the study. Patients were already
      attending 2 health services at the time they developed a cough (period range: 1 -
      552 days), with a median value of 41 days. Factors associated to delay were:
      systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear
      negative. CONCLUSION: The present study indirectly showed the difficulty of
      diagnosing TB in HIV-infected individuals and indicated the need for a better
      assessment of asthenia and chest pain as factors that may be present in co
      infected patients. It is also necessary to discuss the role played by negative
      sputum smear results in diagnosing TB/HIV co-infection as well as the need to
      assess the best approach for drug users with TB/HIV.

PMID- 22958584
TI  - The prevalence of antimicrobial resistance in clinical isolates from Gulf
      Corporation Council countries.
AB  - BACKGROUND: The burden of antimicrobial resistance worldwide is substantial and
      is likely to grow. Many factors play a role in the emergence of resistance. These
      resistance mechanisms may be encoded on transferable genes, which facilitate the
      spread of resistance between bacterial strains of the same and/or different
      species. Other resistance mechanisms may be due to alterations in the chromosomal
      DNA which enables the bacteria to withstand the environment and multiply. Many,
      if not most, of the Gulf Corporation Council (GCC) countries do not have clear
      guidelines for antimicrobial use, and lack policies for restricting and auditing
      antimicrobial prescriptions. OBJECTIVE: The aim of this study is to review the
      prevalence of antibiotic resistance in GCC countries and explore the reasons for
      antibiotic resistance in the region. METHODOLOGY: The PubMed database was
      searched using the following key words: antimicrobial resistance, antibiotic
      stewardship, prevalence, epidemiology, mechanism of resistance, and GCC country
      (Saudi Arabia, Qatar, Bahrain, Kuwait, Oman, and United Arab Emirates). RESULTS:
      From January1990 through April 2011, there were 45 articles published reviewing
      antibiotic resistance in the GCC countries. Among all the GCC countries, 37,295
      bacterial isolates were studied for antimicrobial resistance. The most prevalent
      microorganism was Escherichia coli (10,073/44%), followed by Klebsiella
      pneumoniae (4,709/20%), Pseudomonas aeruginosa (4,287/18.7%), MRSA (1,216/5.4%),
      Acinetobacter (1,061/5%), with C. difficile and Enterococcus representing less
      than 1%. CONCLUSION: In the last 2 decades, E. coli followed by Klebsiella
      pneumoniae were the most prevalent reported microorganisms by GCC countries with
      resistance data.

PMID- 22958585
TI  - Poultry fat decreased fatty acid transporter protein mRNA expression and affected
      fatty acid composition in chickens.
AB  - BACKGROUND: A study was undertaken to examine the effects of poultry fat (PF)
      compared with those of soybean oil (SBO) on intestinal development, fatty acid
      transporter protein (FATP) mRNA expression, and fatty acid composition in broiler
      chickens. A total of 144 day-old male commercial broilers were randomly allocated
      to 2 treatment groups (6 replicates of 12 chicks for each treatment) and fed
      isocaloric diets containing 3.0% PF or 2.7% SBO at 0 to 3 wk and 3.8% PF or 3.5%
      SBO at 4 to 6 wk, respectively. RESULTS: PF had no influence on intestinal
      morphology, weight, or DNA, RNA, or protein concentrations at 2, 4, and 6 wk of
      age. However, compared with SBO, PF significantly decreased FATP mRNA abundance
      at 4 wk (P = 0.009) and 6 wk of age (P < 0.001); decreased liver fatty acid
      binding protein (L-FABP) mRNA abundance at 6 wk of age (P = 0.039); and decreased
      C18:2 (P = 0.015), C18:3 (P < 0.001), C20:2 (P = 0.018), Sigma-polyunsaturated
      fatty acids (Sigma-PUFA) (P = 0.020), and the proportion of PUFA (P < 0.001) in
      the intestinal mucosa and decreased C18:2 (P = 0.010), C18:3 (P < 0.001), C20:2
      (P < 0.001), Sigma-PUFA (P = 0.005), and the proportion of PUFA (P < 0.001) in
      breast muscle at 6 wk of age. CONCLUSIONS: PF decreases FATP and L-FABP mRNA
      expression and decreased the proportion of PUFA in the intestinal mucosa and
      breast muscle.

PMID- 22958587
TI  - Clinical trials in advanced stage lung cancer: a survey of patients' opinion
      about their treatment.
AB  - BACKGROUND: The major aim of this study was to investigate what patients with
      advanced stage lung cancer, enrolled in a clinical trial, thought about their
      treatment. We also wanted to investigate if there exist any characteristics that
      could influence patients' opinion about the clinical trial. PATIENTS AND METHODS:
      Over the period from June 2008 to June 2009, 59 eligible patients were enrolled
      in this study. The major inclusion criteria were: participation in a clinical
      trial, previously treated advanced stage lung cancer, and good performance status
      (ECOG 0-2). All patients were asked to answer a questionnaire designed to
      investigate their impressions about participation in a clinical trial. The
      questionnaire was deposited in a sealed box which was opened at the end of the
      study.We investigated a possible influence of age, gender, education, lung cancer
      stage, chemotherapy line and tumor type on the patients' opinion about some
      aspects of the clinical trial. RESULTS: The majority of the patients were aware
      they were participating in the clinical trial and a significant number of them
      were very satisfied with the treatment. Of the investigated factors, only the
      level of education had a statistically significant influence on some of the
      questions raised in the questionnaire. CONCLUSIONS: Patients participating in
      clinical trials are satisfied with their treatment, ready to proceed with it and
      would recommend it to other patients. It depends mainly on health professionals
      to maintain this level of confidence and justify their trust.

PMID- 22958586
TI  - Red wine and component flavonoids inhibit UGT2B17 in vitro.
AB  - BACKGROUND: The metabolism and excretion of the anabolic steroid testosterone
      occurs by glucuronidation to the conjugate testosterone glucuronide which is then
      excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter
      the rate of testosterone excretion and thus its bioavailability. The aim of this
      study is to investigate if red wine, a common dietary substance, has an
      inhibitory effect on UGT2B17. METHODS: Testosterone glucuronidation was assayed
      using human UGT2B17 supersomes with quantification of unglucuronidated
      testosterone over time using HPLC with DAD detection. The selected red wine was
      analyzed using HPLC; and the inhibitory effects of the wine and phenolic
      components were tested independently in a screening assay. Further analyses were
      conducted for the strongest inhibitors at physiologically relevant
      concentrations. Control experiments were conducted to determine the effects of
      the ethanol on UGT2B17. RESULTS: Over the concentration range of 2 to 8%, the red
      wine sample inhibited the glucuronidation of testosterone by up to 70% over 2
      hours. The ethanol content had no significant effect. Three red wine phenolics,
      identified by HPLC analyses, also inhibited the enzyme by varying amounts in the
      order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio
      of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic
      acid had no effect on the UGT2B17. The most active phenolic was selected for a
      detailed study at physiologically relevant concentrations, and quercetin
      maintained inhibitory activity of 20% at 2 MUM despite a ten-fold excess of
      testosterone. CONCLUSION: This study reports that in an in vitro supersome-based
      assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of
      phenolic dietary substances and therefore may reduce the rate of testosterone
      glucuronidation in vivo. These results highlight the potential interactions of a
      number of common dietary compounds on testosterone metabolism. Considering the
      variety of foodstuffs that contain flavonoids, it is feasible that diet can
      elevate levels of circulating testosterone through reduction in urinary
      excretion. These results warrant further investigation and extension to a human
      trial to delineate the health implications.

PMID- 22958588
TI  - AKI patients have worse long-term outcomes, especially in the immediate post-ICU
      period.
AB  - Acute kidney injury (AKI) is associated with worse outcome in the acute phase of
      acute illness but also in the chronic phase. In a large Danish study in this
      issue of Critical Care, 1-year mortality was higher in patients with AKI than in
      patients without AKI. Mortality was most important during the first 50 days after
      admission to the intensive care unit (ICU), whereas after 2 months the survival
      curves of patients with AKI and those of patients without AKI were similar. The
      reasons for this observation are not clear, but protracted critical illness and
      fragility after acute critical illness probably play important roles. Because we
      see more and more of these patients, they should be the focus of ICU research.
      Consequently, ICU and post-ICU care for these patients requires focus and a more
      integrated approach to the specific problems of these survivors of acute critical
      illness. 

PMID- 22958589
TI  - A systematic review of peripheral nerve injury following laparoscopic colorectal
      surgery.
AB  - AIM: The risk of peripheral nerve injury associated with laparoscopic colorectal
      surgery has not been well established. We aimed to identify the number and type
      of peripheral nerve injuries associated with patient positioning in laparoscopic
      surgery. METHOD: A systematic review of MEDLINE and Embase was undertaken of
      English and non-English language articles. Search terms included the key words:
      laparoscopic, colorectal, nerve injury, nerve damage, brachial plexus, peripheral
      neuropathy, peripheral nerve injury, nerve and colonic injury. Articles were
      included where at least one peripheral nerve injury had been documented related
      to patient positioning at laparoscopic colorectal surgery. Data extraction for
      articles was conducted by two authors, using predefined data fields. RESULTS: Ten
      cases have been reported in the literature. All injuries involved the brachial
      plexus. They were associated with a lengthy procedure and abduction of the arm.
      CONCLUSION: Although rare, the surgeon and theatre team must be aware of the risk
      of peripheral nerve injury when positioning patients for laparoscopic colorectal
      procedures.

PMID- 22958590
TI  - Negative-pressure wound dressings to secure split-thickness skin grafts in the
      perineum.
AB  - Several researches have shown that negative-pressure wound dressings can secure
      split-thickness skin grafts and improve graft survival. However, in anatomically
      difficult body regions such as the perineum it is questionable whether these
      dressings have similar beneficial effects. In this study, we evaluated the
      effects of negative-pressure wound dressings on split-thickness skin grafts in
      the perineum by comparing wound healing rate and complication rate with that of
      tie-over dressings. A retrospective chart review was performed for the patients
      who underwent a split-thickness skin graft to reconstruct perineal skin defects
      between January 2007 and December 2011. After grafting, the surgeon selected
      patients to receive either a negative-pressure dressing or a tie-over dressing.
      In both groups, the initial dressing was left unchanged for 5 days, then changed
      to conventional wet gauze dressing. Graft success was assessed 2 weeks after
      surgery by a single clinician. A total of 26 patients were included in this
      study. The mean age was 56.6 years and the mean wound size was 273.1 cm(2). Among
      them 14 received negative-pressure dressings and 12 received tie-over dressings.
      Negative-pressure dressing group had higher graft taken rate (P = 0.036) and took
      shorter time to complete healing (P = 0.01) than tie-over dressing group. The
      patients with negative-pressure dressings had a higher rate of graft success and
      shorter time to complete healing, which has statistical significance. Negative
      pressure wound dressing can be a good option for effective management of skin
      grafts in the perineum.

PMID- 22958591
TI  - How do patients die in a rehabilitative unit dedicated to advanced respiratory
      diseases?
AB  - BACKGROUND: Evidences on how in-hospital COPD patients are cared in a
      Rehabilitative Respiratory Unit during the last time before death are lacking.
      This observational study was aimed at 1. analyzing the characteristics of
      respiratory patients who die in a Rehabilitative Unit dedicated to advanced care;
      2. studying the available organizational support related to the dying process and
      quality of care in the last week of life. METHODS: Medical records (MR) of
      patients suffering from respiratory disease admitted to a Rehabilitative
      Respiratory Unit during the last seven years (2005-2011) were collected
      retrospectively. Only MR of patients who died of respiratory complications were
      considered. This study describes clinical and demographic variables or
      information about drugs, procedures, health and unprofessional teams,
      intervention and interaction, habits and wishes in the last week of life.
      RESULTS: 110 patients out of 2,615 subjects (4.2%) died during the period of
      observation. 87 out of 110 patients fulfilled the inclusion criteria. They were
      aged, males, retired, severely compromised, with previous stays in an acute
      hospital and with a long stay in our unit. Most of them were married, lived in a
      small village and were cared at home by a caregiver. One third of patients came
      from Intensive Care Units. During the last week of life, hours spent under
      mechanical ventilation were extremely high both for patients under invasive (22.3
      +/- 3.1 hours) and non invasive ventilation (NIV) (17.5 +/- 3.4 hours). The
      number of patients who maintained NIV was twice that of the intubated ones.
      Breathlessness and secretion encumbrance were the main symptoms. Secretion
      management was necessary in more than 50% of the cases. Communication between
      patient and doctor was good in the majority (67%) of the cases. Patient's and
      family wishes, aimed at improving their relationships, were obtained in a high
      percentage (63%) of the cases. Doctors prescribed sedative in a half of patients
      and morphine only in 40% of the cases. Patients mainly died for acute respiratory
      failure (55%) or infective complications (34%), almost all under mechanical
      ventilation. Only a minority of them (28%) reported to have had a discussion
      about end-of-life care with their physician; palliative/end of life decisions
      were taken in 13% of the cases. Sustaining figures such as psychologist (17%) or
      clergy (13%) were marginally required. CONCLUSIONS: The current data have
      confirmed that, also in a Rehabilitative Respiratory setting, quality of end-of
      life care and patient-physician communication need further improvement.

PMID- 22958592
TI  - Prevalence and predictors of urinary tract infection and severe malaria among
      febrile children attending Makongoro health centre in Mwanza city, North-Western
      Tanzania.
AB  - BACKGROUND: In malaria endemic areas, fever has been used as an entry point for
      presumptive treatment of malaria. At present, the decrease in malaria
      transmission in Africa implies an increase in febrile illnesses related to other
      causes among underfives. Moreover, it is estimated that more than half of the
      children presenting with fever to public clinics in Africa do not have a malaria
      infection. Thus, for a better management of all febrile illnesses among under
      fives, it becomes relevant to understand the underlying aetiology of the illness.
      The present study was conducted to determine the relative prevalence and
      predictors of P. falciparum malaria, urinary tract infections and bacteremia
      among under-fives presenting with a febrile illness at the Makongoro Primary
      Health Centre, North-Western Tanzania. METHODS: From February to June 2011, a
      cross-sectional analytical survey was conducted among febrile children less than
      five years of age. Demographic and clinical data were collected using a
      standardized pre-tested questionnaire. Blood and urine culture was done, followed
      by the identification of isolates using in-house biochemical methods.
      Susceptibility patterns to commonly used antibiotics were investigated using the
      disc diffusion method. Giemsa stained thin and thick blood smears were examined
      for any malaria parasites stages. RESULTS: A total of 231 febrile under-fives
      were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10
      25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had
      urinary tract infections, P. falciparum malaria and bacteremia respectively. In
      general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and
      only one child had all three infections. Predictors of urinary tract infections
      (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body
      temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of
      P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025)
      and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the
      common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood
      (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to
      ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4%
      resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to
      meropenem, ciprofloxacin and ceftriaxone respectively. CONCLUSION: Urinary tract
      infection caused by multi drug resistant Escherichia coli was the common cause of
      febrile illness in our setting. Improvement of malaria diagnosis and its
      differential diagnosis from other causes of febrile illnesses may provide
      effective management of febrile illnesses among children in Tanzania.

PMID- 22958595
TI  - Does the asthma control test reflect inflammation?

PMID- 22958594
TI  - Golgi phosphoprotein 2 in physiology and in diseases.
AB  - Golgi phosphoprotein 2 (GOLPH2, also termed GP73 and GOLM1) is a type II
      transmembrane protein residing in the cis and medial-Golgi cisternae. GOLPH2 is
      predominantly expressed in the epithelial cells of many human tissues. Under
      poorly defined circumstances, GOLPH2 can be cleaved and released to the
      extracellular space. Despite of its relatively "young age" since the first
      description in 2000, the physiological and pathological roles of GOLPH2 have been
      the subject that has attracted considerable amount of attention in recent years.
      Here, we review the history of GOLPH2's discovery and the multitude of studies by
      many groups around the world aimed at understanding its molecular, cellular,
      physiological, and pathogenic activities in various settings.

PMID- 22958593
TI  - Association testing of copy number variants in schizophrenia and autism spectrum
      disorders.
AB  - BACKGROUND: Autism spectrum disorders and schizophrenia have been associated with
      an overlapping set of copy number variant loci, but the nature and degree of
      overlap in copy number variants (deletions compared to duplications) between
      these two disorders remains unclear. METHODS: We systematically evaluated three
      lines of evidence: (1) the statistical bases for associations of autism spectrum
      disorders and schizophrenia with a set of the primary CNVs thus far investigated,
      from previous studies; (2) data from case series studies on the occurrence of
      these CNVs in autism spectrum disorders, especially among children, and (3) data
      on the extent to which the CNVs were associated with intellectual disability and
      developmental, speech, or language delays. We also conducted new analyses of
      existing data on these CNVs in autism by pooling data from seven case control
      studies. RESULTS: Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del
      16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk
      factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup
      16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically
      supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup
      16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both
      autism and schizophrenia, although for each of these CNVs statistical
      significance was nominal for tests involving one of the two disorders. For the
      CNVs that were statistically associated with schizophrenia but were not
      statistically associated with autism, a notable number of children with the CNVs
      have been diagnosed with autism or ASD; children with these CNVs also demonstrate
      a high incidence of intellectual disability and developmental, speech, or
      language delays. CONCLUSIONS: These findings suggest that although CNV loci
      notably overlap between autism and schizophrenia, the degree of strongly
      statistically supported overlap in specific CNVs at these loci remains limited.
      These analyses also suggest that relatively severe premorbidity to CNV-associated
      schizophrenia in children may sometimes be diagnosed as autism spectrum disorder.

PMID- 22958596
TI  - Regulatory T cells in induced sputum of asthmatic children: association with
      inflammatory cytokines.
AB  - BACKGROUND AND OBJECTIVE: CD4+CD25+ regulatory T (Treg) cells play an essential
      role in maintaining immune homeostasis. In this study, we investigated whether
      the induced sputum (IS) pool and the function of CD4+CD25+ Treg cells are altered
      in asthma pediatric patients. METHODS: Treg activity was studied in the IS of 40
      asthmatic children. CD3+ cells were analyzed for the expression of FoxP3 mRNA by
      real time reverse transcription-polymerase chain reaction (RT-PCR). IS cells from
      asthmatics and controls were stained for Treg markers and analyzed by flow
      cytometry. We also studied the ability of Treg cells to differentiate monocytes
      toward alternatively activated macrophages (AAM), and to suppress proinflammatory
      cytokines. RESULTS: (i) Mild and moderate asthmatics had significantly decreased
      expression of FoxP3/beta-actin mRNA and decreased proportions of
      CD4+CD25highFoxP3+ cells compared to healthy children; (ii) patients with
      moderate asthma had even lower proportions of FoxP3 expression compared to mild
      asthmatic patients; (iii) monocytes cultured with Treg cells displayed typical
      features of AAM, including up-regulated expression of CD206 (macrophage mannose
      receptor) and CD163 (hemoglobin scavenger receptor), and an increased production
      of chemokine ligand 18 (CCL18). In addition, Treg cells from asthmatics have a
      reduced capacity to suppress LPS-proinflammatory cytokine production from
      monocytes/macrophages (IL-1, IL-6 and TNF-alpha). CONCLUSION: Asthma pediatric
      patients display a decreased bronchial Treg population. The impaired bronchial
      Treg activity is associated with disease severity.

PMID- 22958597
TI  - Modifying patterns of movement in people with low back pain -does it help? A
      systematic review.
AB  - BACKGROUND: Physiotherapy for people with low back pain frequently includes
      assessment and modification of lumbo-pelvic movement. Interventions commonly aim
      to restore normal movement and thereby reduce pain and improve activity
      limitation. The objective of this systematic review was to investigate: (i) the
      effect of movement-based interventions on movement patterns (muscle activation,
      lumbo-pelvic kinematics or postural patterns) of people with low back pain (LBP),
      and (ii) the relationship between changes in movement patterns and subsequent
      changes in pain and activity limitation. METHODS: MEDLINE, Cochrane Central,
      EMBASE, AMI, CINAHL, Scopus, AMED, ISI Web of Science were searched from
      inception until January 2012. Randomised controlled trials or controlled clinical
      trials of people with LBP were eligible for inclusion. The intervention must have
      been designed to influence (i) muscle activity patterns, (ii) lumbo-pelvic
      kinematic patterns or (iii) postural patterns, and included measurement of such
      deficits before and after treatment, to allow determination of the success of the
      intervention on the lumbo-pelvic movement. Twelve trials (25% of retrieved
      studies) met the inclusion criteria. Two reviewers independently identified,
      assessed and extracted data. The PEDro scale was used to assess method quality.
      Intervention effects were described using standardised differences between group
      means and 95% confidence intervals. RESULTS: The included trials showed
      inconsistent, mostly small to moderate intervention effects on targeted movement
      patterns. There was considerable heterogeneity in trial design, intervention type
      and outcome measures. A relationship between changes to movement patterns and
      improvements in pain or activity limitation was observed in one of six studies on
      muscle activation patterns, one of four studies that examined the flexion
      relaxation response pattern and in two of three studies that assessed lumbo
      pelvic kinematics or postural characteristics. CONCLUSIONS: Movement-based
      interventions were infrequently effective for changing observable movement
      patterns. A relationship between changes in movement patterns and improvement in
      pain or activity limitation was also infrequently observed. No independent
      studies confirm any observed relationships. Challenges for future research
      include defining best methods for measuring (i) movement aberrations, (ii)
      improvements in movements, and (iii) the relationship between changes in how
      people move and associated changes in other health indicators such as activity
      limitation.

PMID- 22958598
TI  - Cost-effective treatment of low-risk carcinoma not invading bladder muscle.
AB  - Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's
      known on the subject? and What does the study add? Bladder cancer is one of the
      costliest malignancies to treat throughout the life of a patient. The most cost
      effective management for low-risk non-muscle-invasive bladder cancer is not
      known. The current study shows that employing cystoscopic office fulguration for
      low-risk appearing bladder cancer recurrences can materially impact the cost
      effectiveness of therapy. In a follow-up protocol where office fulguration is
      routinely employed for low-risk bladder cancers, peri-operative intravesical
      chemotherapy may not provide any additional cost-effectiveness benefit.
      OBJECTIVE: To examine the cost-effectiveness of fulguration vs transurethral
      resection of bladder tumour (TURBT) with and without perioperative intravesical
      chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle
      (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the
      use of office-based fulguration for small recurrences rather than traditional
      TURBT. MATERIALS AND METHODS: A Markov state transition model was created to
      simulate treatment of NMIBC with vs without PIC, with recurrence treated by
      formal TURBT vs treatment with fulguration. Costing data were obtained from the
      Medicare Resource Based Relative Value Scale. Data regarding the success of PIC
      were obtained from the peer-reviewed literature, as were corresponding utilities
      for bladder cancer-related procedures. Sensitivity analyses were performed.
      RESULTS: At 5-year follow-up, a strategy of fulguration without PIC was the most
      cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year),
      despite a lower recurrence rate with PIC. Both fulguration strategies dominated
      each TURBT strategy. Sensitivity analysis showed that fulguration without PIC
      dominated all other strategies when the recurrence rate after PIC was increased
      to >=14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more
      competitive with fulguration when the total cost of TURBT declines < US $1175.
      CONCLUSIONS: The present study shows that fulguration without PIC was the most
      cost-effective strategy for treating low-risk NMIBC. The effectiveness of PIC and
      the cost of TURBT can materially impact the cost-effectiveness of the different
      management strategies. These results should be considered in treatment decisions
      in the context of preserving oncological control.

PMID- 22958599
TI  - Engineered cell-cell communication via DNA messaging.
AB  - BACKGROUND: Evolution has selected for organisms that benefit from genetically
      encoded cell-cell communication. Engineers have begun to repurpose elements of
      natural communication systems to realize programmed pattern formation and
      coordinate other population-level behaviors. However, existing engineered systems
      rely on system-specific small molecules to send molecular messages among cells.
      Thus, the information transmission capacity of current engineered biological
      communication systems is physically limited by specific biomolecules that are
      capable of sending only a single message, typically "regulate transcription."
      RESULTS: We have engineered a cell-cell communication platform using
      bacteriophage M13 gene products to autonomously package and deliver heterologous
      DNA messages of varying lengths and encoded functions. We demonstrate the
      decoupling of messages from a common communication channel via the autonomous
      transmission of various arbitrary genetic messages. Further, we increase the
      range of engineered DNA messaging across semisolid media by linking message
      transmission or receipt to active cellular chemotaxis. CONCLUSIONS: We
      demonstrate decoupling of a communication channel from message transmission
      within engineered biological systems via the autonomous targeted transduction of
      user-specified heterologous DNA messages. We also demonstrate that bacteriophage
      M13 particle production and message transduction occurs among chemotactic
      bacteria. We use chemotaxis to improve the range of DNA messaging, increasing
      both transmission distance and communication bit rates relative to existing small
      molecule-based communication systems. We postulate that integration of different
      engineered cell-cell communication platforms will allow for more complex spatial
      programming of dynamic cellular consortia.

PMID- 22958600
TI  - Barley callus: a model system for bioengineering of starch in cereals.
AB  - BACKGROUND: Starch is the most important source of calories for human nutrition
      and the majority of it is produced by cereal farming. Starch is also used as a
      renewable raw material in a range of industrial sectors. It can be chemically
      modified to introduce new physicochemical properties. In this way starch is
      adapted to a variety of specific end-uses. Recombinant DNA technologies offers an
      alternative to starch industrial processing. The plant biosynthetic pathway can
      be manipulated to design starches with novel structure and improved technological
      properties. In the future this may reduce or eliminate the economical and
      environmental costs of industrial modification. Recently, many advances have been
      achieved to clarify the genetic mechanism that controls starch biosynthesis.
      Several genes involved in the synthesis and modification of complex carbohydrates
      in many organisms have been identified and cloned. This knowledge suggests a
      number of strategies and a series of candidate genes for genetic transformation
      of crops to generate new types of starch-based polymers. However transformation
      of cereals is a slow process and there is no easy model system available to test
      the efficiency of candidate genes in planta. RESULTS: We explored the possibility
      to use transgenic barley callus generated from immature embryo for a fast test of
      transgenic modification strategies of starch biosynthesis. We found that this
      callus contains 4% (w/w dw) starch granules, which we could modify by generating
      fully transgenic calli by Agrobacterium-transformation. A Green Fluorescent
      Protein reporter protein tag was used to identify and propagate only fully
      transgenic callus explants. Around 1 - 1.5 g dry weight of fully transgenic
      callus could be produced in 9 weeks. Callus starch granules were smaller than
      endosperm starch granules and contained less amylose. Similarly the expression
      profile of starch biosynthesis genes were slightly different in callus compared
      with developing endosperm. CONCLUSIONS: In this study we have developed an easy
      and rapid in planta model system for starch bioengineering in cereals. We suggest
      that this method can be used as a time-efficient model system for fast screening
      of candidate genes for the generation of modified starch or new types of
      carbohydrate polymers.

PMID- 22958601
TI  - Alveolar proteinosis in Behcet's disease.
AB  - A 51-year-old man with Behcet's disease complained of fever, dry cough and
      dyspnea during exertion. Chest CT showed ground glass opacities with interstitial
      septal thickening in both lungs. Bronchoalveolar lavage (BAL) revealed amorphous
      and lipoproteinaceous material that was periodic acid-Schiff (PAS) stain
      positive. Transbronchial biopsy specimen demonstrated PAS positive alveolar
      eosinophilic material consistent with pulmonary alveolar proteinosis. Serum anti
      granulocyte-macrophage colony stimulating factor (GM-CSF) antibody was negative.
      Recent studies have reported anti-GMCSF not present in the the serum of patients
      with secondary pulmonary alveolar proteinosis (PAP) but they have not reported so
      in patients with idiopathic PAP. We report a case of alveolar proteinosis in the
      setting of Behcet's disease with spontaneous remission.

PMID- 22958602
TI  - Trends of violence among 7th, 8th and 9th grade students in the state of Lara,
      Venezuela: The Global School Health Survey 2004 and 2008.
AB  - BACKGROUND: Violence by young people is one of the most visible forms of violence
      and contributes greatly to the global burden of premature death, injury and
      disability. METHODS: The Global School-based Student Health Survey (GSHS), State
      of Lara, Venezuela (GSHS-Lara) is a school-based surveillance system. It
      comprises a repeated, cross-sectional, self-administered survey drawn from a
      representative sample of 7th to 9th grade students, performed in the school years
      2003-2004 (GSHS-Lara 2004) and 2007-2008 (GSHS-Lara 2008). It explores, among
      other things, a general violence indicator such as school absenteeism due to
      feeling unsafe at school or on the way to or from school for any reason; and more
      specific indicators of violence such as robbery, bullying, physical fights and
      use of weapons, as well as exposure to lectures on how to prevent violence.
      Results are given in terms of prevalence percentage. RESULTS: Absenteeism doubled
      between the two study periods (10.8% to 20.8%). The number of students that were
      a victim of robbery remained high and without change both outside (14.2% and
      14.8%) and inside school (21.7% and 22.0%). The number of victims of bullying was
      high and increasing (33.4% and 43.6%). Bullying associated with being physically
      attacked decreased (18.5% to 14.3%). Physical attacks without active
      participation and not associated with bullying were frequent (21.5%). Physical
      fighting with active participation prevalence remained high and without change
      (27.5% and 28.2%). Carrying a weapon almost doubled (4.3% to 7.1%). Less than 65%
      reported classes for violence prevention. CONCLUSIONS: The GSHS-Lara shows that
      violence is an important public health problem that needs to be addressed by the
      community and its authorities.

PMID- 22958603
TI  - Effect of vitamin-D analogue on albuminuria in patients with non-dialysed chronic
      kidney disease stage 4-5: a retrospective single center study.
AB  - BACKGROUND: The vitamin D receptor activator paricalcitol has been shown to
      reduce albuminuria. Whether this is a unique property of paricalcitol, or common
      to all vitamin D analogues, is unknown. The primary aim of this study was to
      evaluate the effect of alfacalcidol on proteinuria, measured as 24 hour (24 h)
      albuminuria, in patients with chronic kidney disease (CKD) stage 4-5 being
      treated for secondary hyperparathyroidism (sHPT). METHODS: A retrospective single
      center study including adult patients with CKD 4-5, undergoing treatment for sHPT
      with alfacalcidol, with macroalbuminuria in minimum one 24 h urine collection.
      Patients were identified in a prospectively collected database of all patients
      with S-creatinine > 300 MUM or creatinine clearance < 30 ml/min. The observation
      period was from 1st of January 2005 to 31st of December 2009. Phosphate binders
      and alfacalcidol were provided to patients free of charge. RESULTS: A total of
      146 macroalbuminuric patients were identified, and of these, 59 started
      alfacalcidol treatment during the observation period. A 12% reduction in 24 h
      albuminuria was seen after starting treatment. In 19 patients with no change in
      renin-angiotensin-aldosteron-system (RAAS) inhibition, the reduction in
      albuminuria was 16%. The reduction remained stable over time (9%) in a subgroup
      of patients (n = 20) with several urine collections before and after the start of
      alfacalcidol-treatment. CONCLUSION: The present study supports experimental and
      clinical data on antiproteinuric actions of activated vitamin D analogues, and
      suggests that this may be a class-effect.

PMID- 22958605
TI  - A randomized trial to evaluate a launderable bed protection system for hospital
      beds.
AB  - BACKGROUND: Hospital beds are potential reservoirs of bacteria in hospitals.
      Preventing contamination of the bed and providing a cleaner surface should help
      prevent hospital-acquired infections (HAIs). Most hospital beds are cleaned
      between patients (terminal cleaning) using quaternary ammonia compounds (quats).
      OBJECTIVE: The study had two objectives: identify levels of bacterial
      contamination on beds (including the mattress and bed deck) and evaluate a new
      launderable cover. METHODS: Hospital beds on a bariatric surgery ward were
      randomized to either receive or not receive a launderable cover (Trinity
      Guardion, Batesville, IN). Bacterial counts on the surface of the mattress, the
      bed deck, and the launderable cover were then collected using PetrifilmTM Aerobic
      Count Plates (PetrifilmTM, 3MTM, St. Paul, MN, USA) (PetrifilmTM) at three time
      periods (before patient use, after discharge, and after terminal cleaning).
      Standard hospital linen was used in all rooms. RESULTS: The launderable cover (n
      = 28) was significantly cleaner prior to patient use than were the cleaned
      mattresses (n = 38) (1.1 CFU/30 cm2 vs. 7.7 CFU/30 cm2; p = 0.0189). The
      mattresses without launderable covers became significantly contaminated during
      use (7.7 CFU/30 cm2 on admission vs. 79.1 CFU/30 cm2 after discharge; p < 0.001).
      The mattresses with launderable covers did not become contaminated (3.0 CFU/30
      cm2 on admission vs. 2.5 CFU/30 cm2 at discharge; p = 0.703). After terminal
      cleaning, the mattress surface contamination decreased to 12.8 CFU/30 cm2 (median
      3 CFU/30 cm2; SD 7.8), but the bed deck was more contaminated (6.7 CFU/30 cm2
      after discharge compared to 30.9 CFU/30 cm2 after terminal cleaning; p = 0.031).
      CONCLUSIONS: Terminal cleaning fails to eliminate bacteria from the surface of
      the hospital mattress. The launderable cover provides a cleaner surface than does
      terminal cleaning with quats, and the cover protects the bed from contamination
      during use.

PMID- 22958606
TI  - Healthcare-associated infections in European long-term care facilities: how big
      is the challenge?

PMID- 22958604
TI  - Patient-reported selective adherence to heart failure self-care recommendations:
      a prospective cohort study: the Atlanta Cardiomyopathy Consortium.
AB  - Simultaneous adherence with multiple self-care instructions among heart failure
      (HF) patients is not well described. Patient-reported adherence to 8
      recommendations related to exercise, alcohol, medications, smoking, diet, weight,
      and symptoms was assessed among 308 HF patients using the Medical Outcomes Study
      Specific Adherence Scale questionnaire (0="never" to 5="always," maximum
      score=40). A baseline cumulative score of >=32/40 (average >=80%) defined good
      adherence. Clinical events (death/transplantation/ventricular assist device),
      resource utilization, functional capacity (6-minute walk distance), and health
      status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were compared among
      patients with and without good adherence. The mean follow-up was 2.0+/-1.0 years,
      and adherence ranged from 26.3% (exercise) to 89.9% (medications). A cumulative
      score indicating good adherence was reported by 35.7%, whereas good adherence
      with every behavior was reported by 9.1% of patients. Good adherence was
      associated with fewer hospitalizations (all-cause 87.8 vs 107.6; P=.018; HF 29.6
      vs 43.8; P=.007) and hospitalized days (all-cause 422 vs 465; P=.015; HF 228 vs
      282; P<.001) per 100-person-years and better health status (KCCQ overall score
      70.1+/-24.6 vs 63.8+/-22.8; P=.011). Adherence was not associated with clinical
      events or functional capacity. Patient-reported adherence with HF self-care
      recommendations is alarmingly low and selective. Good adherence was associated
      with lower resource utilization and better health status.

PMID- 22958607
TI  - Healthcare-associated infections in long-term care facilities (HALT) in Frankfurt
      am Main, Germany, January to March 2011.
AB  - Healthcare-associated infections (HAIs) are a potentially serious threat to
      elderly people living in longterm care facilities. Therefore, the European HALT
      (Healthcare-associated infections in long-term care facilities) project was
      launched in 2008. HAIs and the use of antibiotics were studied in all 40 nursing
      homes (100% response) in the city of Frankfurt am Main, Germany, from January to
      March 2011, using the HALT protocol. Of the 3,732 residents in the homes, 4.3%
      (n=161) had either signs or symptoms of infections and/or were on oral
      antibiotics. The most common infections were urinary tract infections (n=45;
      1.2%), followed by infections of the respiratory tract (n=41; 1.1%) and skin
      except mycosis (n=25; 0.7%). The overall prevalence of oral antibiotic use was
      2.4% (n=90). The most frequently prescribed oral antibiotics were quinolones
      (n=31), cephalosporins (n=19), penicillins (n=11) and co-trimoxazole (n=11). The
      prevalence of HAIs was about the same as that in a European pilot study carried
      out in November 2009 (5%), but was higher than in several national surveys
      carried out between May and September 2010 (1.6-3.6%).

PMID- 22958608
TI  - Evidence for airborne infectious disease transmission in public ground transport-
      a literature review.
AB  - While guidelines on contact tracing (CT) after exposure to certain infectious
      pathogens during air travel exist, no guidance documents are available on CT in
      response to potential exposure on public ground transport. We reviewed scientific
      and non-scientific literature on transmission of airborne pathogens in public
      ground transport and on factors potentially influencing transmission. We
      identified 32 relevant publications (15 scientific and 17 non-scientific). Most
      of the selected studies dealt with transmission of tuberculosis. However, the
      relation between travel duration, proximity to the index case and environmental
      factors, such as ventilation, on disease transmission in public ground transport
      is poorly understood. Considering the difficulty and probably limited
      effectiveness of CT in ground transport, our results suggest that only
      exceptional circumstances would justify CT. This contrasts with the high level of
      attention CT in air travel seems to receive in international regulations and
      recommendations. We question whether the indication for CT should be revisited
      after a risk-benefit assessment that takes into account exposure in both ground
      and air transport.

PMID- 22958609
TI  - Retrospective screening of serum and cerebrospinal fluid samples from patients
      with acute meningo-encephalitis does not reveal past Japanese encephalitis virus
      infection, Emilia Romagna, Italy, 2011.

PMID- 22958611
TI  - From neurobiology to public policy. Abstracts of the 8th International Conference
      on Early Psychosis. San Francisco, California, USA. October 11-13, 2012.

PMID- 22958613
TI  - Predicting severity of pathological scarring due to burn injuries: a clinical
      decision making tool using Bayesian networks.
AB  - It is important for clinicians to understand which are the clinical signs, the
      patient characteristics and the procedures that are related with the occurrence
      of hypertrophic burn scars in order to carry out a possible prognostic
      assessment. Providing clinicians with an easy-to- use tool for predicting the
      risk of pathological scars. A total of 703 patients with 2440 anatomical burn
      sites who were admitted to the Department of Plastic and Reconstructive Surgery,
      Burn Center of the Traumatological Hospital in Torino between January 1994 and
      May 2006 were included in the analysis. A Bayesian network (BN) model was
      implemented. The probability of developing a hypertrophic scar was evaluated on a
      number of scenarios. The error rate of the BN model was assessed internally and
      it was equal to 24.83%. While classical statistical method as logistic models can
      infer only which variables are related to the final outcome, the BN approach
      displays a set of relationships between the final outcome (scar type) and the
      explanatory covariates (patient's age and gender, burn surface area, full
      thickness burn surface area, burn anatomical area and wound-healing time; burn
      treatment options such as advanced dressings, type of surgical approach, number
      of surgical procedures, type of skin graft, excision and coverage timing). A web
      based interface to handle the BN model was developed on the website
      www.pubchild.org (burns header). Clinicians who registered at the website could
      submit their data in order to get from the BN model the predicted probability of
      observing a pathological scar type. 

PMID- 22958612
TI  - Serum 25(OH)D is inversely associated with metabolic syndrome risk profile among
      urban middle-aged Chinese population.
AB  - BACKGROUND: Vitamin D deficiency is associated with a variety of chronic
      metabolic diseases. Limited evidence regarding vitamin D deficiency exists within
      the Chinese population. The present study aims to examine the association between
      serum vitamin D concentrations and cardiometabolic risk factors in the young and
      middle-aged, urban Chinese population METHODS: The cross-sectional relationships
      between serum 25-hydroxyvitamin D [25(OH)D] concentrations and indices of
      adiposity and cardiometabolic risk factors (e.g., body mass index, waist
      circumference, fasting plasma glucose, etc.) were evaluated in 601 non-diabetic
      adults. RESULT: Vitamin D deficiency or insufficiency was present in 66% of the
      tested population, and serum 25(OH)D levels were lower in patients who were
      overweight/obese or suffered metabolic syndrome when compared to individuals of
      healthy weight without metabolic syndrome (24.08 +/- 8.08 vs 31.70 +/- 11.77
      ng/ml, 21.52 +/- 6.9 vs 31.74 +/- 10.21 ng/ml respectively). 25(OH)D was
      inversely associated with waist circumference, fasting glucose, fasting insulin,
      triglycerides and LDL-cholesterol, and it was positively associated with HDL
      cholesterol in a multivariable-adjusted regression model. CONCLUSION: Vitamin D
      deficiency is common in the young and middle-aged, urban Chinese population, with
      high prevalence in overweight/obese individuals and patients with metabolic
      syndrome. Low vitamin D concentration was associated with indices of adiposity
      and cardiometabolic risk factors. Further studies are warranted to elucidate the
      cause-effect relation between vitamin D status, obesity and related metabolic
      disorders.

PMID- 22958614
TI  - Result of the implementation of multidisciplinary teams in rectal cancer.
AB  - AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all
      major Danish hospitals treating colorectal cancer. The aim was to improve the
      prognosis by multidisciplinary evaluation and decision about surgical and
      oncological treatment, based on medical history, clinical examination, imaging,
      histology and comorbidity. The present study evaluates the effect of the
      introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD:
      A retrospective cohort study was conducted comparing the outcome during the last
      3 years before introduction of MDTs with the first 2 years after (the MDT
      cohort). The national colorectal cancer database, with follow-up recorded by the
      National Patient Registry in September 2010 was used. The end-points included the
      incidence of preoperative radiochemotherapy offered according to the national
      guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence,
      distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred
      and eleven patients were diagnosed with primary rectal cancer in Hvidovre and
      Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of
      preoperative MRI scans increased in the MDT cohort and perioperative mortality
      decreased. More metachronous distant metastases were found in the MDT cohort but
      there was no difference in overall survival. CONCLUSION: There was an improved
      postoperative mortality but no other potential benefits for the patients were
      seen after the implementation of colorectal MDTs.

PMID- 22958615
TI  - Can high-quality palliative care for respiratory patients be improved?

PMID- 22958616
TI  - Preserved reward outcome processing in ASD as revealed by event-related
      potentials.
AB  - BACKGROUND: Problems with reward system function have been posited as a primary
      difficulty in autism spectrum disorders. The current study examined an
      electrophysiological marker of feedback monitoring, the feedback-related
      negativity (FRN), during a monetary reward task. The study advanced prior
      understanding by focusing exclusively on a developmental sample, applying
      rigorous diagnostic characterization and introducing an experimental paradigm
      providing more subtly different feedback valence (reward versus non-reward
      instead of reward versus loss). METHODS: Twenty-six children with autism spectrum
      disorder and 28 typically developing peers matched on age and full-scale IQ
      played a guessing game resulting in monetary gain ("win") or neutral outcome
      ("draw"). ERP components marking early visual processing (N1, P2) and feedback
      appraisal (FRN) were contrasted between groups in each condition, and their
      relationships to behavioral measures of social function and dysfunction, social
      anxiety, and autism symptomatology were explored. RESULTS: FRN was observed on
      draw trials relative to win trials. Consistent with prior research, children with
      ASD exhibited a FRN to suboptimal outcomes that was comparable to typical peers.
      ERP parameters were unrelated to behavioral measures. CONCLUSIONS: Results of the
      current study indicate typical patterns of feedback monitoring in the context of
      monetary reward in ASD. The study extends prior findings of normative feedback
      monitoring to a sample composed exclusively of children and demonstrates that, as
      in typical development, individuals with autism exhibit a FRN to suboptimal
      outcomes, irrespective of neutral or negative valence. Results do not support a
      pervasive problem with reward system function in ASD, instead suggesting any
      dysfunction lies in more specific domains, such as social perception, or in
      response to particular feedback-monitoring contexts, such as self-evaluation of
      one's errors.

PMID- 22958617
TI  - Immunoglobulin genes and diversity: what we have learned from domestic animals.
AB  - This review focuses on the diversity of immunoglobulin (Ig) genes and Ig
      isotypes that are expressed in domestic animals. Four livestock species-cattle,
      sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including
      MU, delta, gamma, epsilon, and alpha. Two poultry species (chickens and ducks)
      express three IgH isotypes, MU, upsilon, and alpha, but not delta. The kappa and
      lambda light chains are both utilized in the four livestock species, but only the
      lambda chain is expressed in poultry. V(D)J recombination, somatic hypermutation
      (SHM), and gene conversion (GC) are three distinct mechanisms by which
      immunoglobulin variable region diversity is generated. Different domestic animals
      may use distinct means to diversify rearranged variable regions of Ig genes.

PMID- 22958618
TI  - Knowledge and practices of people in Bia District, Ghana, with regard to iodine
      deficiency disorders and intake of iodized salt.
AB  - BACKGROUND: Despite numerous educational programmes to create awareness about
      iodized salt and iodine deficiency disorders (IDD), a survey conducted in the
      Western Region of Ghana in 2007 revealed that the goitre rate stood at 18.8%; and
      78.1% of households consumed iodized salt, which is below the goal of the IDD
      programme in Ghana which aimed at 90% household consumption of iodized salt by
      the end of 2005 and sustaining the gains by 2011. It was therefore, considered
      timely to investigate the knowledge levels and the extent of utilization of
      iodized salt among the people living in Bia District, the District with the
      lowest intake (77.4%) of iodized salt based on findings of the 2007 survey.
      METHODS: This was a descriptive cross-sectional study. It was conducted among a
      total of 280 household members, mainly in charge of meal preparation, who were
      interviewed using a structured interview guide. A combination of cluster and
      simple random sampling techniques was used to select the respondents from all the
      seven sub- districts in Bia District. RESULTS: The study revealed that 75.6% of
      households in the district consumed iodized salt (including households described
      as occasional users of iodized salt), and knowledge of iodized salt was quite
      high, as 72% of the respondents knew that not every salt contained iodine. In
      addition, 69.3% indicated that an inadequate intake of iodized salt can lead to
      the development of goitre. Despite the high awareness level, only 64.6% of
      respondents indicated that they exclusively used iodized salt for cooking. The
      main reason given by exclusive users of common salt was that the price of iodized
      salt is a little higher than that of common salt. CONCLUSIONS: Although majority
      of the respondents are aware of the importance of iodized salt and iodine
      deficiency disorders, only 64.6% exclusively used iodized salt, suggesting that
      respondents' high knowledge levels did not necessarily translate into an increase
      in the number of households who used iodized salt. Existing laws and policies on
      universal salt iodization and quality assurance of iodized salt from the
      production stage to the distribution/selling stage should be enforced.

PMID- 22958619
TI  - Anatomically remote muscle contraction facilitates patellar tendon reflex
      reinforcement while mental activity does not: a within-participants experimental
      trial.
AB  - BACKGROUND: The Jendrassik maneuver (JM) is a remote facilitation muscular
      contraction shown to affect amplitude and temporal components of the human
      stretch reflex. Conflicting theoretical models exist regarding the neurological
      mechanism related to its ability to reinforce reflex parameters. One mechanism
      involves the gamma motoneurons of the fusimotor system, which are subject to both
      physical and mental activity. A second mechanism describes reduced alpha
      motoneuron presynaptic inhibition, which is not subject to mental activity. In
      the current study, we determined if mental activity could be used to create a
      reflex facilitation comparable to a remote muscle contraction. METHOD: Using a
      within-participants design, we investigated the relative effect of the JM and a
      successfully employed mental task (Stroop task) on the amplitude and temporal
      components of the patellar tendon reflex. RESULTS: We found that the addition of
      mental activity had no influence on the patellar tendon reflex parameters
      measured, while the JM provided facilitation (increased reflex amplitude,
      decreased total reflex time). CONCLUSION: The findings from this study support
      the view that the mechanism for the JM is a reduction in presynaptic inhibition
      of alpha motoneurons as it is influenced by physical and not mental activity.

PMID- 22958620
TI  - Effects of climatic changes and urban air pollution on the rising trends of
      respiratory allergy and asthma.
AB  - Over the past two decades there has been increasing interest in studies
      regarding effects on human health of climate changes and urban air pollution.
      Climate change induced by anthropogenic warming of the earth's atmosphere is a
      daunting problem and there are several observations about the role of
      urbanization, with its high levels of vehicle emissions and other pollutants, and
      westernized lifestyle with respect to the rising frequency of respiratory
      allergic diseases observed in most industrialized countries.There is also
      evidence that asthmatic subjects are at increased risk of developing
      exacerbations of bronchial obstruction with exposure to gaseous (ozone, nitrogen
      dioxide, sulfur dioxide) and particulate inhalable components of air pollution.A
      change in the genetic predisposition is an unlikely cause of the increasing
      frequency in allergic diseases because genetic changes in a population require
      several generations. Consequently, environmental factors such as climate change
      and indoor and outdoor air pollution may contribute to explain the increasing
      frequency of respiratory allergy and asthma. Since concentrations of airborne
      allergens and air pollutants are frequently increased contemporaneously, an
      enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation
      could account for the increasing frequency of allergic respiratory diseases and
      bronchial asthma.Scientific societies such as the European Academy of Allergy and
      Clinical Immunology, European Respiratory Society and the World Allergy
      Organization have set up committees and task forces to produce documents to
      focalize attention on this topic, calling for prevention measures.

PMID- 22958622
TI  - The European respiratory roadmap.

PMID- 22958621
TI  - Content validity and test-retest reliability of Patient Perception of Intensity
      of Urgency Scale (PPIUS) for overactive bladder.
AB  - BACKGROUND: The Patient Perception of Intensity of Urgency Scale (PPIUS) is a
      patient-reported outcome instrument intended to measure the intensity of urgency
      associated with each urinary or incontinence episode. The objectives of this
      study were to assess the content validity, test-retest reliability, and
      acclimation effect of the PPIUS in overactive bladder (OAB) patients. METHODS:
      Patients undergoing treatment for OAB were recruited to participate in a non
      interventional study by completing a three-day micturition diary including the
      PPIUS for three consecutive weeks. Following completion of the three-week study,
      participants from two select sites also completed a cognitive interview to assess
      their comprehension of the PPIUS. RESULTS: Thirty-nine participants successfully
      completed the three-week test-retest study; twelve of these participants
      completed the cognitive interview. Test-retest reliability was high based on
      intra-class correlation coefficient of 0.95. Among stable patients, the
      difference between the mean ratings of any two weeks was non-significant. Among
      the twelve interview participants, nine found it simple to choose a PPIUS rating
      for each of their micturition episodes and most found the urgency rating
      definitions consistent with their urgency experiences. CONCLUSIONS: The results
      demonstrated content validity based on qualitative interviews, and excellent test
      retest reliability among stable patients. In addition, no acclimation effect was
      observed among stable patients. These findings support the use of the PPIUS as a
      reliable measure of urgency in both clinical trial and real life settings. The
      validity of PPIUS could be further established with future studies investigating
      the relationship between discretely graded urgency and incontinence continuum.

PMID- 22958623
TI  - Heart rate control in patients with chronic atrial fibrillation and heart
      failure.
AB  - The goal of this study was to determine whether aggressive heart rate (HR)
      control in patients with both chronic atrial fibrillation (AF) and heart failure
      (HF) is associated with improved outcomes. HR control is one of the mainstays in
      management of patients with AF. However, rate control can be challenging in
      patients with HF. This study was designed as an interventional clinical trial,
      using patients with chronic AF and left ventricular systolic dysfunction with
      left ventricular ejection fraction <=40% (n=20) as their own controls.
      Intervention consisted of increasing doses of metoprolol succinate to achieve
      target resting HR <70 beats per minute. Clinical data were collected at baseline
      and after intervention, with paired t test used to evaluate statistically
      significant change. After 3 months of intervention, average resting HR decreased
      from 94+/-14 beats per minute to 85+/-12 beats per minute. Average metoprolol
      succinate dose at the end of the study was 121 mg. None of the outcomes improved
      significantly after the intervention, including exercise tolerance (meters walked
      on 6-minute walk test 326+/-83 vs 330+/-86), quality of life (Minnesota Living
      With Heart Failure Questionnaire score of 42.5+/-19 vs 38+/-21), and brain
      natriuretic peptide (242+/-306 pg/mL vs 279+/-395 pg/mL). Aggressive HR control
      was difficult in this group of patients with chronic AF and HF due to patient
      intolerance of increasing doses of beta-blockade, and not associated with
      improved outcomes. Further studies are needed to establish guidelines for target
      HR in patients with chronic AF who also have significant HF.

PMID- 22958624
TI  - Addressing substance abuse and violence in substance use disorder treatment and
      batterer intervention programs.
AB  - BACKGROUND: Substance use disorders and perpetration of intimate partner violence
      (IPV) are interrelated, major public health problems. METHODS: We surveyed
      directors of a sample of substance use disorder treatment programs (SUDPs; N=241)
      and batterer intervention programs (BIPs; N=235) in California (70% response
      rate) to examine the extent to which SUDPs address IPV, and BIPs address
      substance abuse. RESULTS: Generally, SUDPs were not addressing co-occurring IPV
      perpetration in a formal and comprehensive way. Few had a policy requiring
      assessment of potential clients, or monitoring of admitted clients, for violence
      perpetration; almost one-quarter did not admit potential clients who had
      perpetrated IPV, and only 20% had a component or track to address violence. About
      one-third suspended or terminated clients engaging in violence. The most common
      barriers to SUDPs providing IPV services were that violence prevention was not
      part of the program's mission, staff lacked training in violence, and the lack of
      reimbursement mechanisms for such services. In contrast, BIPs tended to address
      substance abuse in a more formal and comprehensive way; e.g., one-half had a
      policy requiring potential clients to be assessed, two-thirds required monitoring
      of substance abuse among admitted clients, and almost one-half had a component or
      track to address substance abuse. SUDPs had clients with fewer resources
      (marriage, employment, income, housing), and more severe problems (both alcohol
      and drug use disorders, dual substance use and other mental health disorders, HIV
      + status). We found little evidence that services are centralized for individuals
      with both substance abuse and violence problems, even though most SUDP and BIP
      directors agreed that help for both problems should be obtained simultaneously in
      separate programs. CONCLUSIONS: SUDPs may have difficulty addressing violence
      because they have a clientele with relatively few resources and more complex
      psychological and medical needs. However, policy change can modify barriers to
      treatment integration and service linkage, such as reimbursement restrictions and
      lack of staff training.

PMID- 22958625
TI  - Effect of home-based pulmonary rehabilitation in patients with idiopathic
      pulmonary fibrosis.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of a home-based
      pulmonary rehabilitation program on the functional outcome parameters in patients
      with idiopathic pulmonary fibrosis (IPF). DESIGN: A prospective study. PATIENTS:
      Seventeen patients diagnosed with IPF. METHODS: A home-based pulmonary
      rehabilitation program was carried out in 17 IPF patients for 12 weeks. Dyspnea
      severity during daily life activities (Medical Research Council Scale), pulmonary
      function (pulmonary function test), exercise capacity (6-minute walking test,
      6MWD), and general health related quality of life (Medical Outcomes Short Form
      36) were evaluated. RESULTS: A significant decrease in perceived dyspnea (p =
      0.003) and leg fatigue (p < 0.05) severities, and an increase in the 6MWD (p =
      0.04) and general health related quality of life scores (health perception,
      physical role, and emotional status subscores) were found after the program (p <
      0.05). CONCLUSION: Home-based pulmonary rehabilitation may reduce dyspnea and
      fatigue severities, and improve exercise capacity and health-related quality of
      life in patients with IPF. In the treatment of IPF patients, home-based pulmonary
      rehabilitation programs should be placed alongside the routine treatment options.

PMID- 22958626
TI  - Pulmonary hypertension diagnosed by echocardiography during idiopathic
      myelofibrosis. A case report and a brief review of the literature.
AB  - Idiopathic myelofibrosis is a rare chronic myeloproliferative disease leading to
      extramedullary hematopoiesis (myeloid metaplasia) with splenomegaly. The liver
      and less frequently other organs including the lung can be involved, therefore
      portal hypertension is relatively common. Pulmonary hypertension (PH) is only
      occasionally reported, although recent studies have suggested an association
      between PH and myeloproliferative disorders.We present a case of PH diagnosis by
      echocardiography in a patient affected by idiopathic myelofibrosis with portal
      hypertension.

PMID- 22958627
TI  - Students' perceptions of males   entering the dietetic profession.
AB  - PURPOSE: Perceptions about males within the dietetic profession were examined
      among students enrolled in dietetic programs. METHODS: A survey was administered
      in classes or online to first- and fourth-year nutrition students in seven
      dietetic programs. Data were subjected to content analysis to determine why
      students thought more males were not choosing dietetics as a career, and what
      impact an increase in males choosing dietetics might have on the profession.
      RESULTS: Barriers to career choice were primarily gendered. Respondents believed
      an increase in male dietitians would be positive, increasing professional
      diversity. Specifically, more male role models would reach more male clients and
      increase male interest in dietetics as a career. Students also foresaw improved
      professional status, leading to greater professional respect and credibility.
      Current stereotyping would be challenged. Perspectives revealed heteronormative
      assumptions that would influence recruitment strategies. CONCLUSIONS: The
      findings suggest that broadening the current sex composition of the profession
      could be beneficial. Attitudes and practices from inside and outside the dietetic
      profession can influence career choice. Further research would allow a more
      nuanced approach to the complex and interrelated issues associated with sex and
      gendered behavior as they relate to the professional complement.

PMID- 22958628
TI  - New dietetic practitioners' perspectives on their education and training.
AB  - PURPOSE: To elucidate the complex phenomenon of dietitian professional
      socialization, we examined factors that influence people's decisions to pursue a
      career in dietetics and how education and training processes influence the
      professional socialization of dietitians. METHODS: Participants (n=12) had less
      than three years of work experience and included alumni from three Canadian
      universities representing different models of entry to practice. Three one-on-one
      interviews were conducted with each participant. RESULTS: The key influencing
      factor in participants' decision to pursue dietetics was the perceived congruence
      between dietetics and other aspects of their lives, including early interests and
      experiences (sports, food and cooking, an eating disorder), career aspirations
      (science, health care), and social networks (the desire to be a professional). A
      pivotal experience during high school or while enrolled in or after graduation
      from another program prompted participants' awareness of and subsequent decision
      to pursue a career in dietetics. Supportive relationships were vital to
      participants' professional socialization. CONCLUSIONS: Recruitment materials and
      education opportunities should help aspiring dietitians develop a clear idea of
      what being a dietitian means. Dietetic educators must attend to the informational
      and relational aspects involved in shaping future practitioners' dietitian
      identities.

PMID- 22958629
TI  - Patient reports of lifestyle advice in primary care.
AB  - PURPOSE: Patients' perceptions of preventive lifestyle in primary care practice
      were examined. METHODS: Practice was assessed with a modified version of the
      Primary Care Assessment Survey (PCAS). This was mailed to random samples of
      patients twice, using practice mailing lists from three Ontario Family Health
      Networks (FHNs). Family Health Networks are physician-based group practices, with
      additional nurse-led telephone advisory services to provide care 24 hours a day,
      seven days a week. The PCAS questionnaire consisted of nine scales (ranging from
      0 to 100). For preventive counselling, additional questions on diet and exercise
      counselling were included to determine how the physician delivered the
      intervention. RESULTS: Of the 2184 survey questionnaires mailed to patients, 22%
      were undeliverable. The response rate was 62% at valid addresses (49% of all
      mailed questionnaires). Of the nine scales, scores (+/- standard deviation) for
      preventive counselling were lowest at 33 +/- 25. In particular, rates of diet
      (37%) and exercise (24%) counselling were low in the FHNs. For most other aspects
      of primary care services, patients generally rated FHNs highly. The majority of
      patients advised about diet and exercise were given verbal advice or pamphlets.
      CONCLUSIONS: In these primary health care organizations, considerable room exists
      for increased preventive counselling, especially about diet and exercise.

PMID- 22958630
TI  - The role of diet in predicting iron deficiency anemia in HIV-positive women.
AB  - PURPOSE: The association between medical, social, and nutritional factors and
      iron deficiency anemia was examined in adult women who had tested positive for
      human immunodeficiency virus (HIV) and were living in the Greater Vancouver Area.
      METHODS: This was a cross-sectional observational study of 102 HIV-positive
      women, aged 19 or older, who were patients of one of three chosen community
      health clinics in Vancouver, British Columbia. Information on usual dietary
      intake and other nutrition-related factors was collected with a short diet
      survey, while medical information and laboratory data were obtained from each
      participant's medical chart. RESULTS: Of the predictors studied, a CD4 cell count
      below 200 cells/uL, a regular menstrual pattern, and African ethnicity were
      associated with an increased risk of iron deficiency anemia. Dietary intake was
      not independently associated with iron status. CONCLUSIONS: Iron deficiency
      anemia in HIV-positive women has multifactorial and complicated causation, but is
      strongly associated with poorer immune status and greater menstrual losses.
      Health disparities in Aboriginal and African women may lead to a higher risk for
      iron deficiency anemia. Routine screening and ongoing nutrition education are
      necessary for the prevention and management of iron deficiency anemia. Further
      research into factors associated with iron deficiency anemia is essential to
      improve prevention and management efforts.

PMID- 22958631
TI  - Household food insecurity and Canadian Aboriginal women's self-efficacy in food
      preparation.
AB  - PURPOSE: Determinants of self-efficacy related to food preparation using store
      bought food were examined in women belonging to the Atikamekw Nation. Also
      examined was whether self-efficacy was associated with household food insecurity.
      METHODS: A cross-sectional survey was conducted with 107 women responsible for
      household food supplies. Two self-efficacy scores were calculated, one for
      healthy food preparation and one for food preparation in general. Household food
      insecurity was measured with an adapted version of the United States Food
      Security Core Module. The other variables were household composition, income
      sources, food supplies, tobacco use, participants' health status, and lifestyle
      and sociodemographic characteristics. Multiple linear regression was used to
      analyze associations between self-efficacy and household food insecurity in 99
      participants. RESULTS: Severe household food insecurity was associated with
      significantly lower healthy food preparation scores in Atikamekw women. Other
      associated variables were food supplies, marital status, alcohol consumption,
      weight status, and understanding of the native language. CONCLUSIONS: Application
      of the concept of self-efficacy contributes to a better understanding of the
      factors influencing food preparation in Atikamekw women. In this study, self
      efficacy in healthy food preparation was linked to food insecurity and obesity,
      particularly in the most serious cases. Efforts to improve diet will require not
      only behavioural interventions, but public policies.

PMID- 22958632
TI  - Food insecurity in Canadian adults receiving diabetes care.
AB  - PURPOSE: The prevalence of adult-level household food insecurity was examined
      among clients receiving outpatient diabetes health care services. METHODS:
      Participants were adults diagnosed with diabetes mellitus, who attended
      individual counselling sessions at Calgary's main clinic from January to April
      2010. Clinicians were trained to administer the Household Food Security Survey
      Module (HFSSM), and did so with clients' assent during their scheduled sessions.
      RESULTS: The prevalence of adult-level household food insecurity among 314
      respondents was 15.0% (95% confidence interval [CI], 11.2 to 19.4); 6.7% (95% CI,
      4.2 to 10.0) of clinic attendees were categorized as severely food insecure. The
      comparable rates obtained in Alberta in 2007 using the same instrument (HFSSM)
      were 5.6% and 1.2%, respectively. CONCLUSIONS: Household food insecurity rates
      among individuals with diabetes in active care are higher than rates reported in
      Canadian population surveys. Severe food insecurity, indicating reduced food
      intake and disrupted eating patterns, may affect this population's ability to
      follow a pattern of healthy eating necessary for effective diabetes management.
      This study reinforces the importance of assessing clients' inability to access
      food because of financial constraints, and indicates that screening with a
      validated measure may facilitate identification of clients at risk.

PMID- 22958633
TI  - Dietary assessment and self-monitoring with nutrition applications for mobile
      devices.
AB  - Nutrition applications for mobile devices (e.g., personal digital assistants,
      smartphones) are becoming increasingly accessible and can assist with the
      difficult task of intake recording for dietary assessment and self-monitoring.
      This review is a compilation and discussion of research on this tool for dietary
      intake documentation in healthy populations and those trying to lose weight. The
      purpose is to compare this tool with conventional methods (e.g., 24-hour recall
      interviews, paper-based food records). Research databases were searched from
      January 2000 to April 2011, with the following criteria: healthy or weight loss
      populations, use of a mobile device nutrition application, and inclusion of at
      least one of three measures, which were the ability to capture dietary intake in
      comparison with conventional methods, dietary self-monitoring adherence, and
      changes in anthropometrics and/or dietary intake. Eighteen studies are discussed.
      Two application categories were identified: those with which users select food
      and portion size from databases and those with which users photograph their food.
      Overall, positive feedback was reported with applications. Both application types
      had moderate to good correlations for assessing energy and nutrient intakes in
      comparison with conventional methods. For self-monitoring, applications versus
      conventional techniques (often paper records) frequently resulted in better self
      monitoring adherence, and changes in dietary intake and/or anthropometrics.
      Nutrition applications for mobile devices have an exciting potential for use in
      dietetic practice.

PMID- 22958634
TI  - Dietary acculturation of Arab immigrants in the Greater Toronto Area.
AB  - PURPOSE: We explored the eating habits of Arab immigrants to determine whether
      they have maintained their traditional diet or have consumed a more Westernized
      diet since immigrating to Canada. METHODS: Arab immigrants who had been in Canada
      for at least eight years and were currently living in the Greater Toronto Area
      were recruited. A sample of 24 Arab immigrants completed a mailed, self
      administered questionnaire, and six participated in a focus group. The focus
      group discussion was transcribed verbatim and results were recorded. Latent
      content analysis was used to analyze, code, and categorize emerging themes.
      RESULTS: Arab immigrants consumed a mixture of both Arabic and Western food and
      perceived their current diet to be healthier than it was before they immigrated
      to Canada. Factors that influenced their food choices included increased
      nutrition health awareness, differences in food preferences and preparation
      methods, and preservation of dietary practices in the new environment.
      CONCLUSIONS: Our findings will help dietitians who work with Arab immigrants to
      become more aware of factors that motivate this group's food choices, and to
      create nutrition programs that are more culturally sensitive.

PMID- 22958635
TI  - Stepping out: dare to step forward,   step back, or just stand still and breathe.
AB  - It is important to step out and make a difference. We have one of the most unique
      and diverse professions that allows for diversity in thought and practice,
      permitting each of us to grow in our unique niches and make significant
      contributions. I was frightened to 'step out' to go to culinary school at the age
      of 46, but it changed forever the way I look at my profession and I have since
      experienced the most enjoyable and innovative career. There are also times when
      it is important to 'step back' to relish the roots of our profession; to help
      bring food back into nutrition; to translate all of our wonderful science into a
      language of food that Canadians understand. We all need to take time to 'just
      stand still and breathe': to celebrate our accomplishments, reflect on our
      actions, ensure we are heading toward our vision, keep the profession vibrant and
      relevant, and cherish one another.

PMID- 22958636
TI  - Decision making around living and deceased donor kidney transplantation: a
      qualitative study exploring the importance of expected relationship changes.
AB  - BACKGROUND: Limited data exist on the impact of living kidney donation on the
      donor-recipient relationship. Purpose of this study was to explore motivations to
      donate or accept a (living donor) kidney, whether expected relationship changes
      influence decision making and whether relationship changes are actually
      experienced. METHODS: We conducted 6 focus groups in 47 of 114 invited
      individuals (41%), asking retrospectively about motivations and decision making
      around transplantation. We used qualitative and quantitative methods to analyze
      the focus group transcripts. RESULTS: Most deceased donor kidney recipients had a
      potential living donor available which they refused or did not want. They mostly
      waited for a deceased donor because of concern for the donor's health (75%). They
      more often expected negative relationship changes than living donor kidney
      recipients (75% vs. 27%, p = 0.01) who also expected positive changes. Living
      donor kidney recipients mostly accepted the kidney to improve their own quality
      of life (47%). Donors mostly donated a kidney because transplantation would make
      the recipient less dependent (25%). After transplantation both positive and
      negative relationship changes are experienced. CONCLUSION: Expected relationship
      changes and concerns about the donor's health lead some kidney patients to wait
      for a deceased donor, despite having a potential living donor available. Further
      research is needed to assess whether this concerns a selected group.

PMID- 22958637
TI  - Public health in the genomic era: will Public Health Genomics contribute to major
      changes in the prevention of common diseases?
AB  - The completion of the Human Genome Project triggered a whole new field of
      genomic research which is likely to lead to new opportunities for the promotion
      of population health. As a result, the distinction between genetic and
      environmental diseases has faded. Presently, genomics and knowledge deriving from
      systems biology, epigenomics, integrative genomics or genome-environmental
      interactions give a better insight on the pathophysiology of common diseases.
      However, it is barely used in the prevention and management of diseases. Together
      with the boost in the amount of genetic association studies, this demands for
      appropriate public health actions. The field of Public Health Genomics analyses
      how genome-based knowledge and technologies can responsibly and effectively be
      integrated into health services and public policy for the benefit of population
      health. Environmental exposures interact with the genome to produce health
      information which may help explain inter-individual differences in health, or
      disease risk. However today, prospects for concrete applications remain distant.
      In addition, this information has not been translated into health practice yet.
      Therefore, evidence-based recommendations are few. The lack of population-based
      research hampers the evaluation of the impact of genomic applications. Public
      Health Genomics also evaluates the benefits and risks on a larger scale,
      including normative, legal, economic and social issues. These new developments
      are likely to affect all domains of public health and require rethinking the role
      of genomics in every condition of public health interest. This article aims at
      providing an introduction to the field of and the ideas behind Public Health
      Genomics.

PMID- 22958638
TI  - Priming the engine of DNA synthesis.
AB  - In this issue of Structure, Rymer and colleagues present the first crystal
      structures of a bacterial DnaG primase with bound substrate NTPs and alarmone
      inhibitors. A thoughtful comparative structural analysis provides important
      insights into the chemical mechanism of primase.

PMID- 22958639
TI  - Conformational changes in motif D of RdRPs as fidelity determinant.
AB  - RNA-dependent RNA polymerases (RdRPs) are the central players in both
      transcription and viral genome replication. Using NMR spectroscopy, Yang and
      colleagues (in this issue of Structure) show that the conformational changes in
      the structural motif D of poliovirus RdRP correlate with the nature of the bound
      nucleotide (correct versus incorrect), with a conserved lysine within this motif
      playing a key role.

PMID- 22958640
TI  - Defense systems up: structure of subtype I-C/Dvulg CRISPR/Cas.
AB  - The study of CRISPR/Cas systems for RNA-based prokaryotic immunity has emerged as
      a rapidly expanding frontier in RNA biology. In this issue of Structure, Nam and
      colleagues provide new clues to deciphering these complex systems in the
      characterization of a subtype I-C CRISPR/Cas complex.

PMID- 22958641
TI  - Using enhanced sampling and structural restraints to refine atomic structures
      into low-resolution electron microscopy maps.
AB  - For a variety of problems in structural biology, low-resolution maps generated by
      electron microscopy imaging are often interpreted with the help of various
      flexible-fitting computational algorithms. In this work, we systematically
      analyze the quality of final models of various proteins obtained via molecular
      dynamics flexible fitting (MDFF) by varying the map-resolution, strength of
      structural restraints, and the steering forces. We find that MDFF can be extended
      to understand conformational changes in lower-resolution maps if larger
      structural restraints and lower steering forces are used to prevent overfitting.
      We further show that the capabilities of MDFF can be extended by combining it
      with an enhanced conformational sampling method, temperature-accelerated
      molecular dynamics (TAMD). Specifically, either TAMD can be used to generate
      better starting configurations for MDFF fitting or TAMD-assisted MDFF (TAMDFF)
      can be performed to accelerate conformational search in atomistic simulations.

PMID- 22958642
TI  - Structure of the pentameric ligand-gated ion channel GLIC bound with anesthetic
      ketamine.
AB  - Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics,
      but a structural understanding of anesthetic action on pLGICs remains elusive.
      GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine.
      The ketamine concentration leading to half-maximal inhibition of GLIC (58 MUM) is
      comparable to that on neuronal nicotinic acetylcholine receptors. A 2.99 A
      resolution X-ray structure of GLIC bound with ketamine revealed ketamine binding
      to an intersubunit cavity that partially overlaps with the homologous antagonist
      binding site in pLGICs. The functional relevance of the identified ketamine site
      was highlighted by profound changes in GLIC activation upon cysteine substitution
      of the cavity-lining residue N152. The relevance is also evidenced by changes in
      ketamine inhibition upon the subsequent chemical labeling of N152C. The results
      provide structural insight into the molecular recognition of ketamine and are
      valuable for understanding the actions of anesthetics and other allosteric
      modulators on pLGICs.

PMID- 22958644
TI  - Optimization of spermatogenesis-regulating hormones in patients with non
      obstructive azoospermia and its impact on sperm retrieval: a multicentre study.
AB  - Study Type - Therapy (outcomes) Level of Evidence 2a What's known on the subject?
      and What does the study add? Clomiphene citrate, hCG and human menopausal
      gonadotropin (hMG) are widely used in treatment of oligospermia, because they
      increase FSH and testosterone which are essential for spermatogenesis. Finding a
      sperm in non-obstructive azoospermia for intracytoplasmic sperm injection is a
      challenge and much effort is required to reach the optimum method of sperm
      retrieval. The study shows that a new protocol of clomiphene citrate, hCG and hMG
      in the treatment of non-obstructive azoospermia achieves an increase in the
      levels of FSH, LH and total testosterone to the target levels that we set. Our
      target level of FSH was 1.5 times its initial level and for serum testosterone it
      was 600-800 ng/dL. Using our described medical treatment protocol in cases of non
      obstructive azoospermia, sperm may be found in patients' ejaculate (~11%) and if
      they remain azoospermic they will have a greater likelihood of sperms being
      obtained in testicular sperm extraction. OBJECTIVE: To evaluate the effect of
      optimizing serum level of follicle-stimulating hormone (FSH), luteinizing hormone
      (LH) and testosterone on sperm retrieval for intracytoplasmic sperm injection.
      PATIENTS AND METHODS: A total of 612 patients with non-obstructive azoospermia
      were evaluated with routine history, physical examination and hormonal
      assessment. Of these, 116 patients underwent microsurgical (micro)-testicular
      sperm extraction (TESE) without any medical treatment and formed the control
      group and the remaining 496 patients were administered clomiphene citrate in a
      titrated dose. Patients were classified into four groups according to their
      response to clomiphene citrate. Group 1: patients with an obvious increase in FSH
      and total testosterone (n = 372). Group 2: patients showing an increase in FSH
      with no or little increase in LH and total testosterone (n = 62). For these
      patients we continued with clomiphene citrate and added human chorionic
      gonadotrophin (hCG). Group 3: patients with no increase in the levels of the
      three hormones (n = 46). Group 4: included patients with continuously decreasing
      serum testosterone levels in response to the increasing dose of clomiphene
      citrate (n = 16). Accordingly, patients in groups 3 and 4 discontinued clomiphene
      citrate and started hCG and human menopausal gonadotropin (hMG). Semen analyses
      were performed periodically and, in patients who remained azoospermic, micro-TESE
      was performed. RESULTS: Sperm were noted in 54 patients (10.9%) in semen analysis
      after treatment in all groups (with no significant difference) at a mean (sd)
      concentration of 2.3 (4.1) million/mL. For the 442 patients who remained
      azoospermic after treatment, successful sperm retrieval was significantly higher
      (57%) compared with the control group (33.6%). CONCLUSION: For patients with non
      obstructive azoospermia, clomiphene citrate, hCG and hMG administration, leading
      to an increased level of FSH and total testosterone, results in an increased rate
      of sperm in the ejaculate and increased likelihood of successful micro-TESE.

PMID- 22958643
TI  - Internally deleted human tRNA synthetase suggests evolutionary pressure for
      repurposing.
AB  - Aminoacyl-tRNA synthetases (AARSs) catalyze aminoacylation of tRNAs in the
      cytoplasm. Surprisingly, AARSs also have critical extracellular and nuclear
      functions. Evolutionary pressure for new functions might be manifested by splice
      variants that skip only an internal catalytic domain (CD) and link noncatalytic N
      and C-terminal polypeptides. Using disease-associated histidyl-tRNA synthetase
      (HisRS) as an example, we found an expressed 171-amino acid protein
      (HisRSDeltaCD) that deleted the entire CD, and joined an N-terminal WHEP to the C
      terminal anticodon-binding domain (ABD). X-ray crystallography and three
      dimensional NMR revealed the structures of human HisRS and HisRSDeltaCD. In
      contrast to homodimeric HisRS, HisRSDeltaCD is monomeric, where rupture of the
      ABD's packing with CD resulted in a dumbbell-like structure of flexibly linked
      WHEP and ABD domains. In addition, the ABD of HisRSDeltaCD presents a distinct
      local conformation. This natural internally deleted HisRS suggests evolutionary
      pressure to reshape AARS tertiary and quaternary structures for repurposing.

PMID- 22958645
TI  - Active liposomal loading of a poorly soluble ionizable drug.

PMID- 22958646
TI  - Concordance between European and US case definitions of healthcare-associated
      infections.
AB  - BACKGROUND: Surveillance of healthcare-associated infections (HAI) is a valuable
      measure to decrease infection rates. Across Europe, inter-country comparisons of
      HAI rates seem limited because some countries use US definitions from the US
      Centers for Disease Control and Prevention (CDC/NHSN) while other countries use
      European definitions from the Hospitals in Europe Link for Infection Control
      through Surveillance (HELICS/IPSE) project. In this study, we analyzed the
      concordance between US and European definitions of HAI. METHODS: An international
      working group of experts from seven European countries was set up to identify
      differences between US and European definitions and then conduct surveillance
      using both sets of definitions during a three-month period (March 1st -May 31st,
      2010). Concordance between case definitions was estimated with Cohen's kappa
      statistic (kappa). RESULTS: Differences in HAI definitions were found for
      bloodstream infection (BSI), pneumonia (PN), urinary tract infection (UTI) and
      the two key terms "intensive care unit (ICU)-acquired infection" and "mechanical
      ventilation". Concordance was analyzed for these definitions and key terms with
      the exception of UTI. Surveillance was performed in 47 ICUs and 6,506 patients
      were assessed. One hundred and eighty PN and 123 BSI cases were identified. When
      all PN cases were considered, concordance for PN was kappa = 0.99 [CI 95%: 0.98
      1.00]. When PN cases were divided into subgroups, concordance was kappa = 0.90
      (CI 95%: 0.86-0.94) for clinically defined PN and kappa = 0.72 (CI 95%: 0.63
      0.82) for microbiologically defined PN. Concordance for BSI was kappa = 0.73 [CI
      95%: 0.66-0.80]. However, BSI cases secondary to another infection site (42% of
      all BSI cases) are excluded when using US definitions and concordance for BSI was
      kappa = 1.00 when only primary BSI cases, i.e. Europe-defined BSI with "catheter"
      or "unknown" origin and US-defined laboratory-confirmed BSI (LCBI), were
      considered. CONCLUSIONS: Our study showed an excellent concordance between US and
      European definitions of PN and primary BSI. PN and primary BSI rates of countries
      using either US or European definitions can be compared if the points highlighted
      in this study are taken into account.

PMID- 22958647
TI  - Excess dietary cholesterol may have an adverse effect on growth performance of
      early post-larval Litopenaeus vannamei.
AB  - One experiment was conducted to determine the nutritive value of cholesterol for
      post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous
      diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0,
      0.5%, 1% and 2% cholesterol, respectively) were fed to triplicate groups of L.
      vannamei shrimp (mean initial wet weight 0.8 mg) for 27 days. After the trial,
      shrimp fed the D1 diet had the best growth performance (final body weights: FBW;
      weight gain: WG; specific growth rate: SGR), while there was no significant
      difference between diet treatments with respect to survival. The whole body crude
      protein level in the shrimp decreased with the increase in dietary cholesterol
      levels, while the whole body crude lipid level in shrimps in the D4 diet
      treatment was significantly higher (P < 0.05) than in other diet treatments.
      Dietary analysis indicated that the D1 diet contained 0.92% cholesterol prior to
      supplementation, which may have satisfied the dietary cholesterol requirement of
      post-larval L. vannamei; excess dietary cholesterol may thus lead to adverse
      effects on the growth performance of post-larval shrimp.

PMID- 22958648
TI  - Estimation of genotyping error rate from repeat genotyping, unintentional
      recaptures and known parent-offspring comparisons in 16 microsatellite loci for
      brown rockfish (Sebastes auriculatus).
AB  - Genotyping errors are present in almost all genetic data and can affect
      biological conclusions of a study, particularly for studies based on individual
      identification and parentage. Many statistical approaches can incorporate
      genotyping errors, but usually need accurate estimates of error rates. Here, we
      used a new microsatellite data set developed for brown rockfish (Sebastes
      auriculatus) to estimate genotyping error using three approaches: (i) repeat
      genotyping 5% of samples, (ii) comparing unintentionally recaptured individuals
      and (iii) Mendelian inheritance error checking for known parent-offspring pairs.
      In each data set, we quantified genotyping error rate per allele due to allele
      drop-out and false alleles. Genotyping error rate per locus revealed an average
      overall genotyping error rate by direct count of 0.3%, 1.5% and 1.7% (0.002,
      0.007 and 0.008 per allele error rate) from replicate genotypes, known parent
      offspring pairs and unintentionally recaptured individuals, respectively. By
      direct-count error estimates, the recapture and known parent-offspring data sets
      revealed an error rate four times greater than estimated using repeat genotypes.
      There was no evidence of correlation between error rates and locus variability
      for all three data sets, and errors appeared to occur randomly over loci in the
      repeat genotypes, but not in recaptures and parent-offspring comparisons.
      Furthermore, there was no correlation in locus-specific error rates between any
      two of the three data sets. Our data suggest that repeat genotyping may
      underestimate true error rates and may not estimate locus-specific error rates
      accurately. We therefore suggest using methods for error estimation that
      correspond to the overall aim of the study (e.g. known parent-offspring
      comparisons in parentage studies).

PMID- 22958649
TI  - Infant mortality in the Flemish Region of Belgium 1999-2008: a time-to-event
      analysis.
AB  - BACKGROUND: When calculating life expectancy, it is usually assumed that deaths
      are uniformly distributed within each of the age intervals. As most of the infant
      deaths are neonatal deaths, this calls for a better assessment for that age
      group. METHODS: The Flemish unified death and birth certificates database for all
      calendar years between 1999 and 2008 was used. A Kaplan-Meier survival analysis
      on a yearly basis was performed to assess the mean time-to-event and to compare
      survival curves between both genders. RESULTS: Over the last years, a slight
      though not steady decrease of the infant mortality rate is observed. In 2008, the
      probability among live births of dying before their first anniversary is 4.60/00
      in boys and 3.50/00 in girls. The large majority (about 85%) of these have died
      in their year of birth. The mean survival time of deaths in their year of birth
      was found to centre around 1 month (about 30 days), which results in a 'mean
      proportion of the calendar year lived' (k1) close to 0.09. Among those who died
      in the year after their year of birth yet before their first anniversary, no such
      concentration in time of the deaths is observed. Differences between the gender
      groups are small and generally not statistically significant. CONCLUSION:
      Statistics Belgium, the federal statistics office, imputes a value for k1 equal
      to 0.1 for infant deaths in their year of birth when calculating life expectancy.
      Our data fully support this value. We think such refinement is generally feasible
      in calculating life expectancy.

PMID- 22958650
TI  - Abnormal social reward processing in autism as indexed by pupillary responses to
      happy faces.
AB  - BACKGROUND: Individuals with Autism Spectrum Disorders (ASD) typically show
      impaired eye contact during social interactions. From a young age, they look less
      at faces than typically developing (TD) children and tend to avoid direct gaze.
      However, the reason for this behavior remains controversial; ASD children might
      avoid eye contact because they perceive the eyes as aversive or because they do
      not find social engagement through mutual gaze rewarding. METHODS: We monitored
      pupillary diameter as a measure of autonomic response in children with ASD (n =
      20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked
      at faces displaying different emotions. Each face displayed happy, fearful, angry
      or neutral emotions with the gaze either directed to or averted from the
      subjects. RESULTS: Overall, children with ASD and TD controls showed similar
      pupillary responses; however, they differed significantly in their sensitivity to
      gaze direction for happy faces. Specifically, pupillary diameter increased among
      TD children when viewing happy faces with direct gaze as compared to those with
      averted gaze, whereas children with ASD did not show such sensitivity to gaze
      direction. We found no group differences in fixation that could explain the
      differential pupillary responses. There was no effect of gaze direction on pupil
      diameter for negative affect or neutral faces among either the TD or ASD group.
      CONCLUSIONS: We interpret the increased pupillary diameter to happy faces with
      direct gaze in TD children to reflect the intrinsic reward value of a smiling
      face looking directly at an individual. The lack of this effect in children with
      ASD is consistent with the hypothesis that individuals with ASD may have reduced
      sensitivity to the reward value of social stimuli.

PMID- 22958651
TI  - A randomized, controlled trial of narrow-band imaging vs high-definition white
      light for adenoma detection in patients at high risk of adenomas.
AB  - AIM: The study aimed to investigate whether narrow-band imaging (NBI) can enhance
      adenoma detection in patients at high risk for adenomas compared with high
      definition white-light endoscopy (WLE). High risk was defined as three or more
      adenomas at last colonoscopy, history of colorectal cancer and positive faecal
      occult blood test. METHOD: Two hundred and fourteen patients were randomized 1:1
      to examination with NBI or WLE. The primary outcome measure was the proportion of
      patients with at least one adenoma detected. Secondary outcomes included total
      adenomas and polyps, flat adenomas, nonadenomatous polyps, advanced adenomas and
      patients with three or five or more adenomas. A post hoc analysis to examine the
      effect of endoscopist and bowel preparation was performed. RESULTS: There was no
      significant difference in the proportion of patients with at least one adenoma:
      NBI 73%vs WLE 66%, odds ratio 1.40 (95% CI 0.78-2.52), P = 0.26. There was no
      significant difference for any secondary outcome measure except for the number of
      flat adenomas which was significantly greater with NBI [comparison ratio 2.66
      (95% CI 1.52-4.63), P = 0.001]. Post hoc analysis indicated that one of three
      endoscopists performed significantly better for adenoma detection with NBI than
      WLE [comparison ratio 1.92 (95% CI 1.07-3.44), P = 0.03]. Good bowel preparation
      was associated with significantly improved adenoma detection with NBI [comparison
      ratio 1.55 (95% CI 1.01-2.22), P = 0.04] but not with fair preparation.
      CONCLUSION: Overall NBI did not improve detection compared with WLE in a group of
      patients at high risk for colorectal adenomas, but specific subgroups might
      benefit.

PMID- 22958652
TI  - Correction: Direct production of biodiesel from high-acid value Jatropha oil with
      solid acid catalyst derived from lignin.

PMID- 22958653
TI  - Simultaneous monitoring of static and dynamic intracranial pressure parameters
      from two separate sensors in patients with cerebral bleeds: comparison of
      findings.
AB  - BACKGROUND: We recently reported that in an experimental setting the zero
      pressure level of solid intracranial pressure (ICP) sensors can be altered by
      electrostatics discharges. Changes in the zero pressure level would alter the ICP
      level (mean ICP); whether spontaneous changes in mean ICP happen in clinical
      settings is not known. This can be addressed by comparing the ICP parameters
      level and waveform of simultaneous ICP signals. To this end, we retrieved our
      recordings in patients with cerebral bleeds wherein the ICP had been recorded
      simultaneously from two different sensors. MATERIALS AND METHODS: During a time
      period of 10 years, 17 patients with cerebral bleeds were monitored with two ICP
      sensors simultaneously; sensor 1 was always a solid sensor while Sensor 2 was a
      solid -, a fluid - or an air-pouch sensor. The simultaneous signals were analyzed
      with automatic identification of the cardiac induced ICP waves. The output was
      determined in consecutive 6-s time windows, both with regard to the static
      parameter mean ICP and the dynamic parameters (mean wave amplitude, MWA, and mean
      wave rise time, MWRT). Differences in mean ICP, MWA and MWRT between the two
      sensors were determined. Transfer functions between the sensors were determined
      to evaluate how sensors reproduce the ICP waveform. RESULTS: Comparing findings
      in two solid sensors disclosed major differences in mean ICP in 2 of 5 patients
      (40%), despite marginal differences in MWA, MWRT, and linear phase magnitude and
      phase. Qualitative assessment of trend plots of mean ICP and MWA revealed shifts
      and drifts of mean ICP in the clinical setting. The transfer function analysis
      comparing the solid sensor with either the fluid or air-pouch sensors revealed
      more variable transfer function magnitude and greater differences in the ICP
      waveform derived indices. CONCLUSIONS: Simultaneous monitoring of ICP using two
      solid sensors may show marked differences in static ICP but close to identity in
      dynamic ICP waveforms. This indicates that shifts in ICP baseline pressure
      (sensor zero level) occur clinically; trend plots of the ICP parameters also
      confirm this. Solid sensors are superior to fluid - and air pouch sensors when
      evaluating the dynamic ICP parameters.

PMID- 22958654
TI  - Keratinocytes in the treatment of severe burn injury: an update.
AB  - Burns are among the most life-threatening physical injuries, in which fast wound
      closure is crucial. The surgical burn care has evolved considerably throughout
      the past decennia resulting in a shift of therapeutic goals. Therapies aiming to
      provide coverage of the burn have been replaced by treatments that have both
      functional as aesthetic outcomes. The standard in treating severe burns is still
      early excision followed by skin grafting. The use of cultured keratinocytes to
      cover extensive burn wounds appeared very promising at first, but the technique
      still has several limitations of which the long time to culture, the major costs,
      the risk of infection and the need for an adequate dermal layer limit clinical
      application. The introduction of dermal substitutes, composite grafts, tissue
      engineering based on stem cell application have been advocated. The aim of this
      review is to assess the use of cultured keratinocytes in terms of technical
      aspects, clinical application, limitations and future perspectives. Cultured
      keratinocytes are expected to keep playing a role in wound healing, especially in
      the field of chronic wounds. In severe burns, despite its limitations,
      keratinocytes can be beneficial if implemented as one of the elements in a
      broader wound management.

PMID- 22958655
TI  - Hematodinium sp. and its bacteria-like endosymbiont in European brown shrimp
      (Crangon crangon).
AB  - BACKGROUND: Parasitic dinoflagellates of the genus Hematodinium are significant
      pathogens affecting the global decapod crustacean fishery. Despite this,
      considerable knowledge gaps exist regarding the life history of the pathogen in
      vivo, and the role of free living life stages in transmission to naive hosts.
      RESULTS: In this study, we describe a novel disease in European brown shrimp
      (Crangon crangon) caused by infection with a parasitic dinoflagellate of the
      genus Hematodinium. This is the second example host within the Infraorder Caridea
      (shrimp) and significantly, the first description within the superfamily
      Crangonoidea. Based upon analysis of the rRNA gene (SSU) and spacers (ITS1), the
      parasite in C. crangon is the same as that previously described infecting
      Nephrops norvegicus and Cancer pagurus from European seas, and to the parasite
      infecting several other commercially important crab species in the Northern
      Hemisphere. The parasite is however distinct from the type species, H. perezi,
      found infecting type hosts (Carcinus maenas and Liocarcinus depurator) from
      nearby sites within Europe. Despite these similarities, the current study has
      also described for the first time, a bacteria-like endosymbiont within dinospore
      stages of the parasite infecting shrimp. The endosymbionts were either contained
      individually within electron lucent vacuoles within the parasite cell cytoplasm,
      or remained in direct contact with the parasite cytoplasm or in some cases, the
      nucleoplasm. In all of these cases, no apparent detrimental effects of
      colonization were observed within the parasite cell. CONCLUSIONS: The presence of
      bacteria-like endosymbionts within dinospore life stages presumes that the
      relationship between the dinoflagellate and the bacteria is extended beyond the
      period of liberation of spores from the infected host shrimp. In this context, a
      potential role of endosymbiosis in the survival of free-living stages of the
      parasite is possible. The finding offers a further intriguing insight into the
      life history of this enigmatic pathogen of marine crustacean hosts and highlights
      a potential for mixotrophy in the parasitic dinoflagellates contained within the
      genus Hematodinium.

PMID- 22958656
TI  - Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia
      guidelines under estimate its severity?
AB  - BACKGROUND: Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed
      patients having malignancy or on immunosuppressive agents. To classify severity,
      the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65
      score of the British Respiratory Society (BTS) and the Pneumonia Severity Index
      (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in
      patients with community-acquired pneumonia (CAP) in Japan. To evaluate how
      correctly these conventional prognostic guidelines for CAP reflect the severity
      of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP.
      METHODS: A total of 21 patients were diagnosed by conventional staining and
      polymerase chain reaction (PCR) for respiratory samples with chest x-ray and
      computed tomography (CT) findings. We compared the severity of 21 patients with
      PCP classified by A-DROP, CURB-65, and PSI. Also, patients' characteristics,
      clinical pictures, laboratory results at first visit or admission and intervals
      from diagnosis to start of specific-PCP therapy were evaluated in both survivor
      and non-survivor groups. RESULTS: Based on A-DROP, 18 patients were classified as
      mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and
      7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or
      moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%)
      died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14
      (100%) developed respiratory failure and 8/14 (57.1%) died. There were no
      significant differences in laboratory results in these groups. The time between
      the initial visit and diagnosis, and the time between the initial visit and
      starting of specific-PCP therapy were statistically shorter in the survivor group
      than in the non-survivor group. CONCLUSIONS: Conventional prognostic guidelines
      for CAP could underestimate the severity of non-HIV PCP, resulting in a
      therapeutic delay resulting in high mortality. The most important factor to
      improve the mortality of non-HIV PCP is early diagnosis and starting of specific
      PCP therapy as soon as possible.

PMID- 22958659
TI  - Do racial and ethnic differences in contraceptive attitudes and knowledge explain
      disparities in method use?
AB  - CONTEXT: Sustained efforts have not attenuated racial and ethnic disparities in
      unintended pregnancy and effective contraceptive use in the United States. The
      roles of attitudes toward contraception, pregnancy and fertility remain
      relatively unexplored. METHODS: Knowledge of contraceptive methods and attitudes
      about contraception, pregnancy, childbearing and fertility were assessed among
      602 unmarried women aged 18-29 at risk for unintended pregnancy who participated
      in the 2009 National Survey of Reproductive and Contraceptive Knowledge. The
      contribution of attitudes to racial and ethnic disparities in effective method
      use was assessed via mediation analysis, using a series of regression models.
      RESULTS: Blacks and Latinas were more likely than whites to believe that the
      government encourages contraceptive use to limit minority populations (odds
      ratio, 2.5 for each). Compared with white women, Latinas held more favorable
      attitudes toward pregnancy (2.5) and childbearing (coefficient, 0.3) and were
      more fatalistic about the timing of pregnancy (odds ratio, 2.3); blacks were more
      fatalistic about life in general (2.0). Only one attitude, skepticism that the
      government ensures contraceptive safety, was associated with contraceptive use
      (0.7), but this belief did not differ by race or ethnicity. Although blacks and
      Latinas used less effective methods than whites (0.3 and 0.4, respectively),
      attitudes did not explain disparities. Lower contraceptive knowledge partially
      explained Latinas' use of less effective methods. CONCLUSIONS: Providing basic
      information about effective methods might help to decrease ethnic disparities in
      use. Research should examine other variables that might account for these
      disparities, including health system characteristics and provider behavior.

PMID- 22958660
TI  - Abortion-seeking minors' views on the Illinois parental notification law: a
      qualitative study.
AB  - CONTEXT: Thirty-seven states have laws in effect that mandate parental
      involvement in adolescent abortion decisions. Little is known about minors'
      opinions of parental involvement laws. METHODS: In-depth interviews were
      conducted with 30 minors presenting for an abortion at one of three Chicago-area
      clinics in 2010. Interviewers described the Illinois parental notification law
      (which was passed in 1995 but is not in effect because of legal challenges) and a
      corresponding judicial bypass option to the minors and asked their opinions about
      them. Interviews were coded and analyzed using content analysis and grounded
      theory methods. RESULTS: Most minors perceived the law negatively, citing fears
      that it would lead to diminished reproductive autonomy for minors, forced
      continuation of pregnancies, adverse parental reactions (including emotional or
      physical abuse) and damaged parental relationships. A few held positive or
      ambivalent opinions, concluding that notifying a trusted adult could provide an
      adolescent with needed support, but that parental involvement should not be
      mandated. Most participants held negative opinions of judicial bypass, describing
      it as overwhelming and logistically complicated, and worrying that some minors
      might go to extreme lengths to avoid the process. CONCLUSIONS: Many minors have
      deep concerns about the potential harm that could result from parental
      involvement laws. These opinions provide a valuable addition to the debate on
      such laws, which purportedly are intended to ensure minors' best interests.

PMID- 22958662
TI  - Tweeting about testing: do low-income, parenting adolescents and young adults use
      new media technologies to communicate about sexual health?
AB  - CONTEXT: Little research exists about adolescents' and young adults' use of new
      media technologies to communicate about sexual health. Understanding how young
      people at high risk for STDs use these technologies can inform media-based
      interventions. METHODS: Between October 2010 and March 2011, a sample of 94 low
      income, parenting adolescents and young adults recruited at clinics in
      Connecticut completed an audio computer-assisted self-interview about their use
      of media technologies, communication with friends about sexual health and
      willingness to use media technologies for such communication. Descriptive
      statistics were calculated; characteristics of those willing and those unwilling
      to communicate were compared in chi-square, t and Mann-Whitney tests. RESULTS:
      Ninety-three percent of participants had mobile phones; 71% used Facebook
      regularly. Participants discussed sexual health more often with close friends
      than with casual friends, and preferred to have such conversations in person (71%
      with close friends and 68% with casual friends), over the phone (52% and 45%) or
      via text message (30% and 28%), rather than through social networking sites (0-9%
      and 2-7%). Fewer than one-third reported being willing to share sexual health
      information with friends through a specific new media technology. Those who were
      willing were predominantly black (59%); of those who were unwilling, 51% were
      Latino. Condom self-efficacy, STD knowledge and number of Facebook friends were
      greater among those who were willing than among those who were unwilling.
      CONCLUSIONS: For conversations about sexual health, young urban parents prefer
      private forms of communication; thus, social networking sites may not aid STD
      interventions.

PMID- 22958663
TI  - What do we know about males and emergency contraception? A synthesis of the
      literature.
AB  - CONTEXT: Unintended pregnancy rates are high in the United States. It is
      important to know whether improving males' access to emergency contraceptive
      pills may help prevent unintended pregnancy, especially in cases of -condom
      failure. METHODS: A search of the PubMed, PsycINFO and Cumulative Index of
      Nursing and Allied Health Literature databases was conducted to identify studies
      published from January 1980 to April 2011 concerning males and emergency
      contraception. Forty-three studies met the specified criteria and examined
      relevant knowledge, attitudes, beliefs, intentions or behaviors, from the
      perspectives of males, clinicians or pharmacists. RESULTS: The proportion of
      males who were familiar with emergency contraception ranged from 38% among
      teenagers to 65-100% among adults. Small proportions reported that they and their
      partner had used or discussed using emergency contraceptive pills (13-30%) or
      that they themselves had ever purchased them (11%). Most providers (77-85%)
      reported general knowledge about emergency contraceptives, but the proportions
      who knew the time frame within which the pills can be prescribed were smaller (28
      63%). Most males approved of emergency contraceptive use following contraceptive
      failure (74-82%) or unprotected sex (59-65%), or in cases of rape (85-91%), but
      both pharmacists and college students reported concerns that females might feel
      pressured to use the method. No study examined clinicians' attitudes and
      behaviors (e.g., counseling or advance provision) regarding males and emergency
      contraception. CONCLUSIONS: Studies are needed to determine whether male
      involvement in emergency contraception can reduce rates of unintended pregnancy
      and to assess health professionals' ability to counsel males about the method.

PMID- 22958661
TI  - Parents' support and knowledge of their daughters' lives, and females' early
      sexual initiation in nine European countries.
AB  - CONTEXT: Associations between early sexual initiation and parental support and
      knowledge have not been uniformly tested in multiple European population-based
      samples. Understanding such associations is important in efforts to discourage
      females' early sex. METHODS: Data were compiled for 7,466 females aged 14-16 who
      participated in the 2005-2006 Health Behaviors in School-Aged Children survey in
      nine countries (Austria, Finland, Greece, Hungary, Iceland, Lithuania, Romania,
      Spain and Ukraine). Univariate, bivariate and multivariable analyses were run
      with standard error corrections and weights to assess how sexual initiation
      before age 16 was related to maternal and paternal support and knowledge of daily
      activities. RESULTS: Prevalence of early sexual initiation ranged from 7% (in
      Romania) to 35% (in Iceland). In bivariate analyses, maternal and paternal
      support were significantly negatively related to adolescent females' early sexual
      initiation in most countries. In models with demographic controls, parental
      support was negatively associated with early sexual initiation (odds ratio, 0.8
      for maternal and 0.7 for paternal). After parental knowledge was added, early
      sexual initiation was no longer associated with parental support, but was
      negatively associated with maternal and paternal knowledge (0.7 for each). These
      patterns held across countries. CONCLUSIONS: Parental knowledge largely explained
      negative associations between parental support and early initiation, suggesting
      either that knowledge is more important than support or that knowledge mediates
      the association between support and early sex.

PMID- 22958664
TI  - Contraceptive features preferred by women at high risk of unintended pregnancy.
AB  - CONTEXT: Available contraceptives are not meeting many women's needs, as is
      evident by high levels of typical-use failure, method switching and
      discontinuation. To improve women's satisfaction with contraceptive methods,
      determining what features they prefer and how these preferences are satisfied by
      available methods and methods under development is crucial. METHODS: The
      importance of 18 contraceptive method features was rated by 574 women seeking
      abortions--a group at high risk of having unprotected intercourse and unintended
      pregnancies--at six clinics across the United States in 2010. For each available
      and potential method, the number of features present was assessed, and the
      percentage of these that were "extremely important" to women was calculated.
      RESULTS: The three contraceptive features deemed extremely important by the
      largest proportions of women were effectiveness (84%), lack of side effects (78%)
      and affordability (76%). For 91% of women, no method had all of the features they
      thought were extremely important. The ring and the sponge had the highest
      percentage of features that women deemed extremely important (67% each). Some
      streamlined modes of access and new contraceptive technologies have the potential
      to satisfy women's preferences. For example, an over-the-counter pill would have
      71% of extremely important features, and an over-the-counter pericoital pill,
      68%; currently available prescription pills have 60%. CONCLUSION: The
      contraceptive features women want are largely absent from currently available
      methods. Developing and promoting methods that are more aligned with women's
      preferences presumably could help increase satisfaction and thereby encourage
      consistent and effective use.

PMID- 22958665
TI  - The public health risks of crisis pregnancy centers.

PMID- 22958673
TI  - Fit for high altitude: are hypoxic challenge tests useful?
AB  - Altitude travel results in acute variations of barometric pressure, which induce
      different degrees of hypoxia, changing the gas contents in body tissues and
      cavities. Non ventilated air containing cavities may induce barotraumas of the
      lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss.
      Commercial air planes keep their cabin pressure at an equivalent altitude of
      about 2,500 m. This leads to an increased respiratory drive which may also result
      in symptoms of emotional hyperventilation. In patients with preexisting
      respiratory pathology due to lung, cardiovascular, pleural, thoracic
      neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an
      additional hypoxic stress may induce respiratory pump and/or heart failure.
      Clinical pre-altitude assessment must be disease-specific and it includes
      spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In
      patients with abnormal values we need, in addition, measurements of hemoglobin,
      pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is
      sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not
      without danger for patients with respiratory insufficiency, we prefer primarily a
      hyperoxic challenge. The supplementation of normobaric O2 gives us information on
      the acute reversibility of the arterial hypoxemia and the reduction of
      ventilation and pulmonary hypertension, as well as about the efficiency of the
      additional O2-flow needed during altitude exposure. For difficult judgements the
      performance of the test in a hypobaric chamber with and without supplemental O2
      breathing remains the gold standard. The increasing numbers of drugs to treat
      acute pulmonary hypertension due to altitude exposure (acetazolamide,
      dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants,
      prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists)
      including mechanical aids to reduce periodical or insufficient ventilation during
      altitude exposure (added dead space, continuous or bilevel positive airway
      pressure, non-invasive ventilation) call for further randomized controlled trials
      of combined applications.

PMID- 22958674
TI  - Unilateral adrenal hyperplasia is a usual cause of primary hyperaldosteronism.
      Results from a Swedish screening study.
AB  - BACKGROUND: The existence of unilateral adrenal hyperplasia (AH) has been
      considered a rare cause of primary hyperaldosteronism (PA). METHODS: In a
      prospective study we screened for PA in a non-selected (NSP) and selected
      hypertensive population (SP), to define the cause of PA. We included 353
      consecutive patients with hypertension; age 20 to 88 years, 165 women and 188
      men, from a university-based Hypertension and Nephrology Outpatient clinics (123
      SP) and two primary care centres, (230 NSP) from the same catch-up area. Serum
      aldosterone and plasma renin activity (PRA) were measured and the ARR calculated.
      Verifying diagnostic procedure was performed in patients with both elevated
      aldosterone and ARR. Patients diagnosed with PA were invited for adrenal venous
      sampling (AVS) and offered laparoscopic adrenalectomy when AVS found the disease
      to be unilateral. RESULTS: After screening, 46 patients, 13% of the whole
      population (22.8% SP and 7.8% NSP) had aldosterone and ARR above the locally
      defined cut-off limits (0.43 nmol/l and 1.28 respectively). After diagnostic
      verification, 20 patients (6%) had PA, (14.5% SP and 1.4% NSP). Imaging
      diagnostic procedures with CT-scans and scintigraphy were inconclusive. AVS,
      performed in 15 patients verified bilateral disease in 4 and unilateral in 10
      patients. One AVS failed. After laparoscopic adrenalectomy, 4 patients were found
      to have adenoma and 5 unilateral AH. One patient denied operation. CONCLUSION:
      The prevalence of PA was in agreement with previous studies. The study finds
      unilateral PA common and unilateral AH as half of those cases. As may be
      suspected PA is found in much higher frequency in specialised hypertensive units
      compared to primary care centers. AVS was mandatory in diagnosis of unilateral
      PA.

PMID- 22958675
TI  - Clinical analysis of 68 patients with pulmonary mycosis in China.
AB  - BACKGROUND: Due to the lack of specific clinical manifestations and imaging
      features, the diagnosis of pulmonary mycosis is difficult. This study aimed to
      investigate the pathogens, clinical manifestations, imaging features, diagnosis
      and management of pulmonary mycosis. METHODS: Data on 68 patients diagnosed as
      pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were
      collected and their clinical manifestations, radiographic characterization,
      diagnostic methods and management were analyzed. RESULTS: All patients were
      diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary
      aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was
      performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and
      computerized tomography (CT) guided percutaneous needle biopsy in 11 (16.2%).
      Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38
      (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%)
      were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52
      cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and
      diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before
      pathological examination occurred. Surgical resection was performed in 38
      patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was
      administered, and 20 patients (29.4%) experienced complete responses or partial
      responses. CONCLUSION: The main pathogens of pulmonary mycosis are Aspergillus,
      followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends
      on pathological examination. The clinical manifestations, imaging features,
      diagnostic methods and management differ depending on the pathogens. Satisfactory
      therapy can be obtained by both antifungal and surgical treatment.

PMID- 22958676
TI  - Is regional species diversity bounded or unbounded?
AB  - Two conflicting hypotheses have been proposed to explain large-scale species
      diversity patterns and dynamics. The unbounded hypothesis proposes that regional
      diversity depends only on time and diversification rate and increases without
      limit. The bounded hypothesis proposes that ecological constraints place upper
      limits on regional diversity and that diversity is usually close to its limit.
      Recent evidence from the fossil record, phylogenetic analysis, biogeography, and
      phenotypic disparity during lineage diversification suggests that diversity is
      constrained by ecological processes but that it is rarely asymptotic. Niche space
      is often unfilled or can be more finely subdivided and still permit coexistence,
      and new niche space is often created before ecological limits are reached. Damped
      increases in diversity over time are the prevalent pattern, suggesting the need
      for a new 'damped increase hypothesis'. The damped increase hypothesis predicts
      that diversity generally increases through time but that its rate of increase is
      often slowed by ecological constraints. However, slowing due to niche limitation
      must be distinguished from other possible mechanisms creating similar patterns.
      These include sampling artifacts, the inability to detect extinctions or declines
      in clade diversity with some methods, the distorting effects of correlated
      speciation-extinction dynamics, the likelihood that opportunities for allopatric
      speciation will vary in space and time, and the role of undetected natural
      enemies in reducing host ranges and thus slowing speciation rates. The taxonomic
      scope of regional diversity studies must be broadened to include all ecologically
      similar species so that ecological constraints may be accurately inferred. The
      damped increase hypothesis suggests that information on evolutionary processes
      such as time-for-speciation and intrinsic diversification rates as well as
      ecological factors will be required to explain why regional diversity varies
      among times, places and taxa.

PMID- 22958677
TI  - Body composition in obstructive sleep apneahypopnea syndrome bio-impedance
      reflects the severity of sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by
      repeated breathing pauses during sleep and is closely associated with obesity.
      Body fat is known to be a predictive factor for OSAHS and its severity. AIM: To
      study the correlation between the severity of OSAHS and body composition
      measurements. METHODS: 30 patients with OSAHS (21 men, 9 women, mean age 45.1
      years, mean apnea-hypopnea index = 29.6/hour) were included in the study after
      full polysomnography. They were divided into 3 groups according to the apnea
      hypopnea index (AHI): mild OSAHS (mean AHI 10.9/h), moderate OSAHS (mean AHI
      23.9/h) and severe OSAHS (mean AHI 53.9/h). Body composition (body fat, body
      water and dry lean mass) was assessed using bioelectric impedance assay (BIA).
      Other measurements included neck and abdominal circumferences and body mass index
      (BMI). Pearson's coefficient (r) was used to express correlations between AHI and
      the following parameters: BMI, neck and abdominal circumferences, body fat, dry
      lean mass, and body water. Wilcoxon Sum-of-Ranks (Mann-Whitney) test for
      comparing unmatched samples was used to compare anthropometric and body
      composition measurements between groups. RESULTS: The correlation between AHI and
      BMI was weak (r = 0.38). AHI correlated moderately with neck circumference (r =
      0.54), with neck circumference corrected by height (r = 0.60), and more strongly
      with body fat (r = 0.67), with body water (r = 0.69) and with abdominal
      circumference (r = 0.75). There was a strong negative correlation between AHI and
      dry lean mass (r = - 0.92). There were significant differences in body fat, body
      water, neck circumference corrected by height and abdominal circumference
      (Wilcoxon Sum-of-Ranks, p < 0.01), between mild and severe OSASH groups, but not
      in BMI (Wilcoxon Sumof-Ranks, W = 86.5; p = 0.17). CONCLUSIONS: In our study, the
      severity of OSAHS correlated with body fat and with body water more strongly than
      with general and cervical obesity. Abdominal adiposity may predict OSAHS severity
      better than neck circumference.

PMID- 22958679
TI  - How can the results of a qualitative process evaluation be applied in management,
      improvement and modification of a preventive community trial? The IHHP Study.
AB  - BACKGROUND: This study reports the results of the qualitative process evaluation
      (PE) of the Isfahan Healthy Heart Program (IHHP), an integrated community-based
      trial for prevention and control of non-communicable diseases in Iran. METHODS:
      The study explored the overall quality of program implementation. The
      participants, including designers of IHHP, stakeholders and community members (n
      = 60) were purposefully recruited from the intervention areas. Data collected
      from semi-structured interviews and field notes were analyzed using a modified
      thematic analysis. RESULTS: Four main themes were identified. Our findings
      highlighted the key role of the resources as both facilitating and hindering
      factors. IHHP directors faced incompatibilities arising from negative
      perceptions/attitudes which resulted in decreased adherence to the program. Hence
      various strategies were used to motivate, strengthen and organize the human
      workforce implementing the program. CONCLUSION: Recommendations arising from
      evaluation of the program were used in subsequent stages of implementation.
      Qualitative research is an important component of community trials which can
      improve their implementation.

PMID- 22958680
TI  - A swannish song?

PMID- 22958678
TI  - A pragmatic cluster randomized controlled trial of early intervention for chronic
      obstructive pulmonary disease by practice nurse-general practitioner teams: Study
      Protocol.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of
      disability, hospitalization, and premature mortality. General practice is well
      placed to diagnose and manage COPD, but there is a significant gap between
      evidence and current practice, with a low level of awareness and implementation
      of clinical practice guidelines. Under-diagnosis of COPD is a world-wide problem,
      limiting the benefit that could potentially be achieved through early
      intervention strategies such as smoking cessation, dietary advice, and exercise.
      General practice is moving towards more structured chronic disease management,
      and the increasing involvement of practice nurses in delivering chronic care.
      DESIGN: A pragmatic cluster randomised trial will test the hypothesis that
      intervention by a practice nurse-general practitioner (GP) team leads to improved
      health-related quality of life and greater adherence with clinical practice
      guidelines for patients with newly-diagnosed COPD, compared with usual care.
      Forty general practices in greater metropolitan Sydney Australia will be
      recruited to identify patients at risk of COPD and invite them to attend a case
      finding appointment. Practices will be randomised to deliver either practice
      nurse-GP partnership care, or usual care, to patients newly-diagnosed with
      COPD.The active intervention will involve the practice nurse and GP working in
      partnership with the patient in developing and implementing a care plan involving
      (as appropriate), smoking cessation, immunisation, pulmonary rehabilitation,
      medication review, assessment and correction of inhaler technique, nutritional
      advice, management of psycho-social issues, patient education, and management of
      co-morbidities.The primary outcome measure is health-related quality of life,
      assessed with the St George's Respiratory Questionnaire 12 months after
      diagnosis. Secondary outcome measures include validated disease-specific and
      general health related quality of life measures, smoking and immunisation status,
      medications, inhaler technique, and lung function. Outcomes will be assessed by
      project officers blinded to patients' randomization groups. DISCUSSION: This
      study will use proven case-finding methods to identify patients with undiagnosed
      COPD in general practice, where improved care has the potential for substantial
      benefit in health and healthcare utilization. The study provides the capacity to
      trial a new model of team-based assessment and management of newly diagnosed COPD
      in Australian primary care. TRIAL REGISTRATION: ACTRN12610000592044?

PMID- 22958682
TI  - Thieves of the state.

PMID- 22958683
TI  - Social aspects of alcohol consumption in Russia.

PMID- 22958684
TI  - Port Elizabeth's tertiary care reaches crisis point.

PMID- 22958685
TI  - Hope at last for foreign nurse recruitment?

PMID- 22958686
TI  - 'Help us unite healthcare' - Motsoaledi appeal to BHF.

PMID- 22958687
TI  - Bridging the healthcare delivery divide.

PMID- 22958689
TI  - Achieving weight loss and avoiding obesity.
AB  - The effect of the vast variety of nutrients on metabolic outcome and health is
      complex. A large number of factors play a role in the type and quantity of food
      consumed in free-living conditions. It is therefore obvious that prescribing a
      restrictive diet regimen that favours 1 or 2 nutrients at the expense of the
      others is a poor tool to manage long-term health and weight.

PMID- 22958690
TI  - Human tissue and organ transplant provisions: chapter 8 of the National Health
      Act and its Regulations, in effect from March 2012 - what doctors must know.
AB  - Where provisions that were in the Human Tissue Act have been left out of the
      National Health Act they have been included in its regulations. However, new
      provisions in the latter Act provide strict controls for the transplantation of
      organs into non-South African citizens or non-permanent residents, and outlaw the
      charging of fees for human organs. The provisions also expand the list of persons
      who can give consent to donations from deceased persons to include 'partners',
      who now take precedence over all other relatives except spouses. Some of the
      matters in the Human Tissue Act that were not covered by the National Health Act
      have now been included in the regulations, such as: (i) the parties responsible
      for determining death of a person whose organs are to be removed for
      transplantation purposes; (ii) the requirement that tissue must be harvested
      within 24 hours from donated bodies; (iii) the removal of eye tissue; (iv) the
      exclusivity of rights in respect of tissue donations; and (v) confidentiality and
      publicity regarding tissue and organ transplants.

PMID- 22958691
TI  - Partial relief from the regulatory vacuum involving human tissues through
      enactment of chapter 8 of the National Health Act and regulations thereto.
AB  - Human tissue legislation is complex. An exhaustive understanding of the law,
      thorough understanding of human tissue biology and pathophysiology and an
      appreciation of the diversity of the areas covered in this field, is critical.
      The importance of interdisciplinary co-operation in the drafting, interpretation
      and implementation of legislation in this area cannot be overemphasized. Several
      factors underscore this, including the complexity and volume of the information
      involved, rapid advances in science, reciprocal dependence of the law and science
      on one another for relevance and accuracy, and above all the need to ensure that
      the patient's well-being and safety are not compromised. The development of
      technology also must be encouraged in a non-obstructive legislative setting.

PMID- 22958692
TI  - Can a new paediatric sub-specialty improve child health in South Africa?
AB  - Compared with other middle-income countries, child health in South Africa is in a
      poor state, and should be addressed by focusing on the health care needs of all
      children across a system or region. Paediatricians have had little effect on this
      situation, partly because their training is not aligned with South African needs.
      The proposed re-engineering of primary health care will be limited by the skewed
      distribution of staff and the lack of suitable skills. A 'community' placement
      during specialist training, and the creation of a sub-specialty in Community
      Paediatrics and Child Health, could address the skills shortage and possibly
      attract health personnel to under-served areas through creating an appropriate
      career path. This proposal would also support the Department of Health's
      encouraging plans to re-engineer primary health care.

PMID- 22958693
TI  - The cardiovascular health of the nation - should we be advocating a low
      carbohydrate, high-fat diet?

PMID- 22958694
TI  - Law reform dealing with blood, tissues, organ transplants and health research: a
      lagging legal framework that is strangling innovation.

PMID- 22958695
TI  - Reducing the sodium content of high-salt foods: effect on cardiovascular disease
      in South Africa.
AB  - BACKGROUND: Average salt intake in South African (SA) adults, 8.1 g/day, is
      higher than the recommended 4 - 6 g/day recommended by the World Health
      Organization. Much salt consumption arises from non-discretionary intake (the
      highest proportion from bread, with contributions from margarine, soup mixes and
      gravies). This contributes to an increasing burden of hypertension and
      cardiovascular disease (CVD). OBJECTIVES: To provide SA-specific information on
      the number of fatal (stroke, ischaemic heart disease and hypertensive heart
      disease) and non-fatal CVD events that would be prevented each year following a
      reduction in the sodium content of bread, soup mix, seasoning and margarine.
      METHODS: Based on the potential sodium reduction in selected products, we
      calculated the expected change in population-level systolic blood pressure (SBP)
      and mortality due to CVD and stroke. RESULTS: Proposed reductions would decrease
      the average salt intake by 0.85 g/person/day. This would result in 7 400 fewer
      CVD deaths and 4 300 less non-fatal strokes per year compared with 2008. Cost
      savings of up to R300 million would also occur. CONCLUSIONS: Population-wide
      strategies have great potential to achieve public health gains as they do not
      rely on individual behaviour or a well-functioning health system. This is the
      first study to show the potential effect of a salt reduction policy on health in
      SA.

PMID- 22958696
TI  - Voluntary informed consent and good clinical practice for clinical research in
      South Africa: ethical and legal perspectives.
AB  - Most differences, shortcomings and contradictions regarding voluntary informed
      consent for participation in clinical research relate to the South African
      specific guidance documents, i.e. South African Guidelines for Good Practice in
      the Conduct of Clinical Trials with Human Participants in South Africa (2006) and
      Ethics in Health Research: Principles, Structures and Processes (2004). These
      documents do not fulfil all the ethical and legal requirements for voluntary
      informed consent for clinical research participation in South Africa.
      International guidance documents reflect the minimum of the ethical requirements
      for the conduct of clinical research. Country-specific documents should be
      updated and aligned with relevant legislative and legal principles of that
      jurisdiction to ensure that research participants are adequately protected. The
      South African-specific guidance documents therefore require revision to address
      these deficiencies.

PMID- 22958697
TI  - Drivers' risk profile indicates the need for a graduated driving licence in South
      Africa.
AB  - BACKGROUND: Current driver mortality estimates do not consider the great
      differences in exposure across the population, giving a false impression that
      driver deaths are lowest in the youngest age group. Interventions to reduce risk
      among the younger age group include graduated driver licensing (GDL) - a three
      phase licensing system for novice drivers consisting of a learner's permit, a
      provisional license, and a full license. OBJECTIVES: We calculated driver
      fatality rates per 10 000 registered drivers in each age group and assessed the
      need for stricter licensing conditions for novice and younger drivers. METHODS:
      Age-specific driver mortality rates were calculated using Western Cape Province
      2008 mortuary data. The total number of licensed drivers in each age group served
      as the denominator. Incidence rate ratios were calculated using the age group of
      65 - 79 years as the reference. Chi-square test of trend on incidence rate ratios
      for the age groups was done. Statistical significance was set as p<0.05. RESULTS:
      There were 339 driver deaths; mean age was 39.4+/-13.8 years, and males accounted
      for 80% of the deaths. Age-specific driver mortality rates were highest in the
      youngest age group (15 - 19 years). There was a significant progressive decrease
      (except for the age group 45 - 49 years) in the risk of death from road traffic
      injuries with increasing age compared with the age group >= 65 years (chi2 for
      trend p<0.0001). CONCLUSION; This study showed a relationship between driver's
      mortality risk and younger age, and underscores the need for introduction of a
      GDL programme in South Africa.

PMID- 22958698
TI  - The burden of sickle cell disease in Cape Town.
AB  - BACKGROUND: South Africa has a low incidence of sickle cell disease (SCD).
      However, its demographics are changing because of immigration from sub-Saharan
      African countries where SCD is prevalent. OBJECTIVES: We aimed to determine the
      frequency of SCD presenting to the Haematology/Oncology Service at Red Cross War
      Memorial Children's Hospital in Cape Town and to measure the associated disease
      burden. METHODS: This was a retrospective cross-sectional study of patients first
      attending the Haematology Service between January 2001 and June 2010. RESULTS: A
      total of 58 SCD patients were identified, with an annual frequency that increased
      over the study period by 300 - 400%. Up to 93.1% (n=54) were originally from
      other African countries, mainly the Democratic Republic of Congo (62.1%, n=36).
      One patient had sickle D-Punjab genotype, and all the other patients had the
      homozygous sickle cell anaemia genotype (Hb SS). Their haematological parameters
      demonstrated a normocytic anaemia with high white cell counts. The mean number of
      clinic visits per patient per year was 22.2 (range 0 - 64), and the mean number
      of hospital admissions per patient per year was 1.2 (range 0 - 5). All the
      patients were on antibiotic prophylaxis. The majority had at least one blood
      transfusion (65.5%, n=38), and a significant proportion required intravenous
      analgesia on admission (29.3%, n=17) and hydroxyurea treatment (36.2%, n=21).
      CONCLUSIONS: Over the past 10 years the frequency of SCD has increased
      considerably, imposing a significant burden and new challenges to the health
      services in Cape Town.

PMID- 22958699
TI  - Impact of 20-day strike in Polokwane Hospital (18 August - 6 September 2010).
AB  - BACKGROUND: Doctors' strikes have a negative effect on hospital performance
      indicators. Hospital mortality during such strikes is the most important
      indicator. OBJECTIVE: To determine the effects of the 2010 strike on Polokwane
      Hospital. METHODS: Information was collected from the Hospital Information
      System, Polokwane Hospital Casualty Department, wards and theatres. RESULTS:
      During the 20-day strike, a total of 262 patients were admitted to Polokwane
      Hospital, with 40 patients to the surgical department; 96 operations were
      performed in the hospital and 40 in the surgical department; and 50 deaths were
      reported in the hospital (8 deaths in the surgical department). During 20 days of
      a non-striking period in May 2010, there were 975 admissions to the hospital,
      with 125 to the surgical department. In the entire hospital, 340 operations were
      performed, and 79 in the surgical department. For this period, 61 deaths were
      reported in the hospital and 12 in the surgical department. CONCLUSIONS: The
      total number of patients admitted to the hospital and the surgical department
      during the strike was significantly lower than during a non-striking situation.
      Total mortality during the strike in Polokwane Hospital decreased, compared with
      the normal situation, but it increased when judged against emergency cases.
      However, when mortality was qualified by the number of admissions, it showed a
      significant increase. Strikes seriously and significantly affect service
      delivery.

PMID- 22958700
TI  - Cervical intra-epithelial neoplasia in HIV-positive women after excision of
      transformation zone - does the grade change?
AB  - OBJECTIVE: After previously reporting the presence of disease by cytology
      findings after treatment for cervical intra-epithelial neoplasia (CIN) in 64.6%
      of HIV-infected women and in 13.0% of HIV-negative women, we aimed to determine
      the severity of cytological disease after treatment in HIV-infected women.
      METHODS: We studied HIV-infected (N=571) women treated at the Colposcopy Clinic
      at Chris Hani Baragwanath Hospital, Gauteng, between April 2003 and December
      2006. We compared the initial histology results with Pap smears >=6 months later,
      and evaluated factors associated with reduction in the grade of disease. RESULTS:
      Mean age was 36.68 (SD+7.33) years; mean parity was 2 (SD+1.46); mean CD4+ count
      was 242.70 cells/mm3 (SD+187.56); 262 (45.80%) were receiving antiretroviral
      treatment. Persistent disease was detected on the repeat Pap smear in 199
      (65.03%); of these, 223 (72.88%) were of a lesser grade than in the original
      histology results. Of the 152 with histologically confirmed CIN3, 67 (44.08%) had
      improved to a lesser grade, and 54 (44.63%) had normal cytology results. Among
      the latter two subject groups (n=141) who had CIN2 histologically, 91 (64.53%)
      had improved, 29 (20.57%) remained unchanged, and 20 (14.88%) had CIN3; 13
      (4.25%) patients with CIN1 returned for follow-up; 11 (84.62%) of these had
      normal Pap smears and 2 (15.38%) had CIN3. CONCLUSION: Recurrences were of a
      lesser degree than initial histology results. This reduction in the grade of
      disease was related to CD4+ count, complete excision and parity. Antiretroviral
      therapy use did not improve outcome, perhaps owing to low initial CD4 counts.

PMID- 22958701
TI  - South African measles outbreak 2009 - 2010 as experienced by a paediatric
      hospital.
AB  - INTRODUCTION: Between 2009 and 2010, South Africa experienced a major measles
      outbreak, with more than 18 000 confirmed cases reported to the National
      Institute of Communicable Diseases. METHODS: We studied measles admissions during
      the outbreak to Red Cross War Memorial Children's Hospital, Cape Town, between 1
      November 2009 and 31 July 2010. Factors associated with mortality were
      retrospectively identified from notification records and hospital admissions
      data. Multivariate logistic regression was used to investigate potential risk
      factors for death. RESULTS: In total, 1 861 children were diagnosed with measles;
      552 (30%) were admitted to hospital. The most common reason for admission was
      pneumonia (379 (68%)) and/or diarrhoea (262 (48%)). The median age at admission
      was 7.36 months (interquartile range (IQR) 5.0 - 10.7). The median duration of
      admission was 4 days (IQR 2 - 6); total hospital admission time was 3 746 days
      (10.3 child-years). HIV status was known in 404 (73%) children: 39/400 (14%) were
      HIV-infected. Eighteen children died (3% of all admissions); 15 (83%) of them
      were less than 1 year old. In the regression model, HIV-infection (adjusted odds
      ratio (aOR) 7.55, 95% confidence interval (CI) 2.27 - 25.12) and female sex (aOR
      3.86, 95% CI 1.26 - 11.84) were associated with higher odds of death.
      CONCLUSIONS: There was a large paediatric admission burden during the 2009 - 2010
      measles outbreak in Cape Town; young children were predominantly affected. HIV
      infected children had a significantly higher case fatality.

PMID- 22958702
TI  - Case fatality of patients with stroke over a 12-month period post stroke.
AB  - INTRODUCTION: Stroke is among the top 4 causes of death in South Africa and the
      top 10 leading causes of disability worldwide. There is a dearth of literature on
      stroke incidence, prevalence and outcome in sub-Saharan Africa. We aimed to
      establish the case fatality of stroke patients over a 12-month period post
      discharge from hospital. METHODS: A total of 200 patients with first-time
      ischaemic stroke were recruited from Chris Hani Baragwanath Academic Hospital and
      followed up for 12 months. The Barthel Index (BI) and Rivermead Mobility Index
      (RMI) were used to establish patient functional ability and, by inference, stroke
      severity. Follow-up assessments were performed at 3, 6 and 12 months post
      discharge. Data analysis was largely descriptive in nature. RESULTS: Thirty-eight
      per cent of patients died within the 12 month follow-up period; 25.5% within 3
      months of discharge. The average length of hospital stay was 6 days. Low BI
      scores at discharge were observed in the majority of patients who died.
      CONCLUSION: The 12-month cumulative mortality was high (highest at the 3-month
      follow-up). The short hospital stay and poor functional ability of the patients
      post stroke possibly left them vulnerable to bed-rest complications, such as
      chest infections and pressure sores.

PMID- 22958703
TI  - Recall of lost-to-follow-up pre-antiretroviral therapy patients in the Eastern
      Cape: effect of mentoring on patient care.
AB  - BACKGROUND: In 2011 an experienced HIV nurse from the UK was deployed for 3
      months to act as a mentor to nurses learning to initiate antiretroviral therapy
      (ART) in primary care clinics in a small town in the Eastern Cape, South Africa.
      METHODS: A review of existing pre-ART patient files (N=286) was carried out and
      lost-to-follow-up (LTFU) HIV patients were recalled. RESULTS: Only 24% of
      patients had attended the clinics within the preceding 6 months and 20% had not
      attended for longer than 2 years. Two lay counsellors visited 222 patients to
      encourage them to return to care; 65/286 (23%) were untraceable, 11/286 (4%) had
      relocated, 30/286 (10%) declined, and 8/286 (3%) had died. In the 6 weeks
      following recall, 51/286 patients (18%) returned to the clinics. CD4 count
      testing was repeated and screening for tuberculosis (TB) and other opportunistic
      infections was performed for all patients; ART was initiated in 13/51 (25%), 1
      patient tested positive for TB, and isionazid (INH) prophylaxis was initiated in
      23/51 (45%). The cost of recall was R130/patient. Within 6 months, all clinics
      began providing full ART services, 17 professional nurses were mentored and they
      initiated ART in 55 patients. CONCLUSIONS: Mentoring plays an important role in
      professional nurse training and support. Recall of LTFU patients is feasible and
      effective in improving ART services in rural settings.

PMID- 22958707
TI  - Prognostic value of epidermal growth factor receptor expression in operable non
      small cell lung carcinoma.
AB  - BACKGROUND AND AIM: Increased expression of the epidermal growth factor receptor
      (EGFR) in non-small cell lung cancer (NSCLC), supporting the tumor growth by a
      possible endocrine mechanism, affects patient survival negatively. We designed a
      study to test EGFR expression by immunohistochemistry (IHC) in resected stage I
      II NSCLC and to correlate its overexpression with survival. METHODS: EGFR
      expression was evaluated in 98 consecutive NSCLC patients after complete
      resection (53 squamous cell carcinomas, 40 adenocarcinomas, 5 large cell
      carcinomas: stage I, 57 (58%) and stage II, 41 (42%). IHC was used to examine the
      expression of EGFR in resected lung tumor samples obtained from these patients,
      who had no pre- or post-operative chemotherapy or radiotherapy. Univariate and
      multivariate analyses were performed for factors influencing patient survival.
      RESULTS: EGFR was expressed in 51 (52%) of 98 NSCLC samples. More squamous tumors
      (61%) were EGFR-positive than adenocarcinomas (38%) (p = 0.038). There was a
      statistically significant correlation between EGFR expression and stage (p =
      0.04). No difference was found between EGFR positive and negative tumors in the 5
      year overall survival (57% vs. 73%, p = 0.13). CONCLUSION: The level of EGFR
      expression in tumors was not a successful predictor of survival in resected
      NSCLC.

PMID- 22958708
TI  - Glutamine and glutamate supplementation raise milk glutamine concentrations in
      lactating gilts.
AB  - Glutamine is the most abundant amino acid in milk, and lactation is associated
      with increased glutamine utilization both for milk synthesis and as a fuel for
      the enlarged small intestine. A number of recent studies have indicated that
      lactation is accompanied by a mild catabolic state in which skeletal muscle
      proteins are degraded to provide amino acids that are used to synthesize
      additional glutamine. In this study we tested the hypothesis that supplemental L
      glutamine or the commercially available glutamine supplement Aminogut (2.5% by
      weight mixed into daily feed) provided to gilts from 30 days prior to parturition
      until 21 days post-parturition would prevent a decrease in skeletal muscle
      glutamine while increasing the glutamine content of the milk. Muscle glutamine
      content decreased (P < 0.05) in control animals during lactation but this was
      prevented by supplementation with either L-glutamine or Aminogut. In this study,
      neither lactation nor supplementation had any effect on plasma glutamine or
      glutamate content. Free glutamine, and the total glutamine plus glutamate
      concentrations in milk from the control and the Aminogut group rose (P < 0.05)
      during the first 7 days of lactation, with milk concentrations in the L-glutamine
      supplemented group showing a similar trend (P = 0.053). Milk glutamate remained
      constant between day 7 and 21 of lactation in the control and L-glutamine
      supplemented groups, but by day 21 of lactation the free glutamine, glutamate,
      and glutamine plus glutamate concentrations in milk from Aminogut-treated gilts
      were higher than those of control gilts. Thus dietary glutamine supplementation
      can alleviate the fall in intramuscular glutamine content during lactation in
      gilts, and may alleviate some of the catabolic effects of lactation. Furthermore,
      the increased milk glutamine content in the supplemented gilts may provide
      optimum nutrition for piglet development.

PMID- 22958710
TI  - Elucidation of the effect of ionic liquid pretreatment on rice husk via
      structural analyses.
AB  - BACKGROUND: In the present study, three ionic liquids, namely 1-butyl-3
      methylimidazolium chloride ([BMIM]Cl), 1-ethyl-3-methylimidazolium acetate
      ([EMIM]OAc), and 1-ethyl-3-methylimidazolium diethyl phosphate ([EMIM]DEP), were
      used to partially dissolve rice husk, after which the cellulose were regenerated
      by the addition of water. The aim of the investigation is to examine the
      implications of the ionic liquid pretreatments on rice husk composition and
      structure. RESULTS: From the attenuated total reflectance Fourier transform
      infrared (ATR FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron
      microscopy (SEM) results, the regenerated cellulose were more amorphous, less
      crystalline, and possessed higher structural disruption compared with untreated
      rice husk. The major component of regenerated cellulose from [BMIM]Cl and
      [EMIM]DEP pretreatments was cellulose-rich material, while cellulose regenerated
      from [EMIM]OAc was a matrix of cellulose and lignin. Cellulose regenerated from
      ionic pretreatments could be saccharified via enzymatic hydrolysis, and resulted
      in relatively high reducing sugars yields, whereas enzymatic hydrolysis of
      untreated rice husk did not yield reducing sugars. Rice husk residues generated
      from the ionic liquid pretreatments had similar chemical composition and
      amorphousity to that of untreated rice husk, but with varying extent of surface
      disruption and swelling. CONCLUSIONS: The structural architecture of the
      regenerated cellulose and rice husk residues showed that they could be used for
      subsequent fermentation or derivation of cellulosic compounds. Therefore, ionic
      liquid pretreatment is an alternative in the pretreatment of lignocellulosic
      biomass in addition to the conventional chemical pretreatments.

PMID- 22958709
TI  - Dysglycemia but not lipids is associated with abnormal urinary albumin excretion
      in diabetic kidney disease: a report from the Kidney Early Evaluation Program
      (KEEP).
AB  - BACKGROUND: The relationship between glycemic control and lipid abnormalities
      with urinary albumin-creatinine ratio (ACR) in chronic kidney disease (CKD)
      patients with diabetes mellitus (DM) is unknown. We sought to investigate the
      association of dyslipidemia and glycemic control with levels of albuminuria in
      the National Kidney Foundation (NKF) Kidney Early Evaluation Program (KEEP)
      participants with DM and CKD stage 3 or higher. METHODS: We performed a cross
      sectional study of 6639 eligible KEEP patients with DM and CKD Stage 3 to 5 from
      June 2008 to December 2009. Multivariate logistic regression was used to evaluate
      the association of lipid parameters (per 10 mg/dl change in serum level) and
      glycosylated hemoglobin (HbA1c) values with three degrees of albuminuria normo
      (<30 mg/g), micro (30 to 300 mg/g) and macro (>300 mg/g). RESULTS: 2141 KEEP
      participants were included. HbA1c levels were strongly associated with micro
      albuminuria (compared to normo-albuminuria) and macro-albuminuria (compared to
      normo-albuminuria and micro-albuminuria). Each 1.0% increase in HbA1c increased
      the odds of micro-albuminuria by 32% (OR 1.32, 95% CI 1.23-1.42) and the odds of
      macro-albuminuria (vs. microalbuminuria) by 16% (OR 1.16, 95% CI 1.05-1.28). Only
      increases in serum HDL were associated with decreased odds of micro-albuminuria;
      otherwise, the association between other components of the serum lipid profile
      with urinary ACR did not reach statistical significance. CONCLUSION: In this
      cross-sectional study of 2141 KEEP participants with DM and CKD stages 3-5,
      overall glycemic control but not lipids were associated with abnormal urinary
      albumin excretion, a marker of increased risk for progressive disease.

PMID- 22958711
TI  - "Save Antibiotics, Save lives": an Indian success story of infection control
      through persuasive diplomacy.
AB  - BACKGROUND: Carbapenem resistant Enterobacteriaceae is a worldwide threat, with
      increasing prevalence in many countries. Restricted usage of higher end
      antibiotics, especially carbapenem is of great importance in tackling these super
      bugs. Purpose of this retrospective study was to analyse the impact of antibiotic
      stewardship activities on the prevalence of carbapenem resistant
      Enterobacteriaceae in our hospital. FINDINGS: In the first Quarter of 2009,
      average usage of carbapenem group of antibiotics was 955 vials a month while in
      2010, the usage dropped to 745 vials per month. Carbapenem resistant E.coli rate
      dropped from 3.7% in 2009 to 1.6% in 2010 and Klebsiella rate reduced from 6% in
      2009 to 3.6% in 2010. CONCLUSIONS: Strict antibiotic stewardship strategies in
      conjunction with good infection control practices are useful in restricting
      higher end antibiotic usage and reducing the prevalence of carbapenem resistant
      Enterobacteriaceae.

PMID- 22958712
TI  - Social determinants of sex differences in disability among older adults: a multi
      country decomposition analysis using the World Health Survey.
AB  - INTRODUCTION: Women represent a growing proportion of older people and experience
      increasing disability in their longer lives. Using a universally agreed
      definition of disability based on the International Classification of
      Functioning, Disability and Health, this paper examines how, apart from age,
      social and economic factors contribute to disability differences between older
      men and women. METHODS: World Health Survey data were analyzed from 57 countries
      drawn from all income groups defined by the World Bank. The final sample
      comprises 63638 respondents aged 50 and older (28568 males and 35070 females).
      Item Response Theory was applied to derive a measure of disability which ensured
      cross country comparability. Individuals with scores at or above a threshold
      score were those who experienced significant difficulty in their everyday lives,
      irrespective of the underlying etiology. The population was then divided into
      "disabled" vs. "not disabled". We firstly computed disability prevalence for
      males and females by socio-demographic factors, secondly used multiple logistic
      regression to estimate the adjusted effects of each social determinant on
      disability for males and females, and thirdly used a variant of the Blinder
      Oaxaca decomposition technique to partition the measured inequality in disability
      between males and females into the "explained" part that arises because of
      differences between males and females in terms of age and social and economic
      characteristics, and an "unexplained" part attributed to the differential effects
      of these characteristics. RESULTS: Prevalence of disability among women compared
      with men aged 50+ years was 40.1% vs. 23.8%. Lower levels of education and
      economic status are associated with disability in women and men. Approximately
      45% of the sex inequality in disability can be attributed to differences in the
      distribution of socio-demographic factors. Approximately 55% of the inequality
      results from differences in the effects of the determinants. CONCLUSIONS: There
      is an urgent need for data and methodologies that can identify how social,
      biological and other factors separately contribute to the health decrements
      facing men and women as they age. This study highlights the need for action to
      address social structures and institutional practices that impact unfairly on the
      health of older men and women.

PMID- 22958714
TI  - Time for physicians to be aware of molecular genetic testing. Report from the 3rd
      Viareggio Health Festival.

PMID- 22958715
TI  - Long-term alterations of striatal parvalbumin interneurons in a rat model of
      early exposure to alcohol.
AB  - BACKGROUND: Exposure to alcohol in utero is a known cause of mental retardation.
      Although a certain degree of motor impairment is always associated with fetal
      alcohol spectrum disorder, little is known about the neurobiological basis of the
      defective motor control. We have studied the striatal interneurons containing
      parvalbumin in a rat model of fetal alcohol spectrum disorder. METHODS: Newborn
      rats received ethanol by inhalation from postnatal day two through six and
      parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal
      day 60. The spatial distribution of parvalbumin interneurons was studied using
      Voronoi spatial tessellation and their dendritic trees were completely
      reconstructed. RESULTS: Parvalbumin interneurons of ethanol-treated animals
      showed a clustered spatial distribution similar to that observed in control
      animals. The dendritic tree of parvalbumin interneurons was significantly reduced
      in ethanol-treated animals, as compared with controls. CONCLUSIONS: Striatal
      parvalbumin interneurons are crucial components of the brain network serving
      motor control. Therefore, the shrinkage of their dendrites could contribute to
      the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.

PMID- 22958716
TI  - Improving the role of CT in diagnosing perforated appendicitis: can appendiceal
      air help?

PMID- 22958717
TI  - Hemodynamic effects of furosemide on renal perfusion as evaluated by ASL-MRI.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to investigate the short-term
      effects of furosemide on renal perfusion by using arterial spin labeling (ASL)
      magnetic resonance imaging. MATERIALS AND METHODS: Eleven healthy human subjects
      were enrolled in the study. The measurement of renal blood flow (RBF) was
      performed by applying an ASL technique with flow-sensitive alternating inversion
      recovery spin preparation and a single-shot fast spin-echo imaging strategy on a
      3.0-T magnetic resonance scanner. For all subjects, the ASL magnetic resonance
      images were obtained before agent injection as a baseline scan. Then 20 mg of
      furosemide was injected intravenously. Postfurosemide ASL images were acquired
      following administration to evaluate the renal hemodynamic response. RESULTS:
      Postinjection scans showed that cortical RBF decreased from 366.59 +/- 41.19
      mL/100 g/min at baseline to 314.33 +/- 48.83 mL/100 g/min at 10 minutes after the
      administration of furosemide (paired t test, P = .04 vs baseline), and medullary
      RBF decreased from 118.59 +/- 24.69 mL/100 g/min at baseline to 97.38 +/- 18.40
      mL/100 g/min at 10 minutes after the administration of furosemide (paired t test,
      P = .01 vs baseline). There was a negative correlation between the furosemide
      induced diuretic effect and the reduction of RBF (Spearman's r = -0.61).
      CONCLUSIONS: The dominant hemodynamic effect of furosemide on the kidney is
      associated with a decrease in both cortical and medullary blood perfusion.
      Furthermore, the quantitative ASL technique may provide an alternative way to
      noninvasively monitor the change in renal function due to furosemide
      administration.

PMID- 22958713
TI  - DNA barcodes identify marine fishes of Sao Paulo State, Brazil.
AB  - Anthropogenic impacts are an increasing threat to the diversity of fishes,
      especially in areas around large urban centres, and many effective conservation
      actions depend on accurate species identification. Considering the utility of DNA
      barcoding as a global system for species identification and discovery, this study
      aims to assemble a DNA barcode reference sequence library for marine fishes from
      the coastal region of Sao Paulo State, Brazil. The standard 652 bp 'barcode'
      fragment of the cytochrome c oxidase subunit I (COI) gene was PCR amplified and
      bidirectionally sequenced from 678 individuals belonging to 135 species. A
      neighbour-joining analysis revealed that this approach can unambiguously
      discriminate 97% of the species surveyed. Most species exhibited low
      intraspecific genetic distances (0.31%), about 43-fold less than the distance
      among species within a genus. Four species showed higher intraspecific
      divergences ranging from 2.2% to 7.6%, suggesting overlooked diversity. Notably,
      just one species-pair exhibited barcode divergences of <1%. This library is a
      first step to better know the molecular diversity of marine fish species from Sao
      Paulo, providing a basis for further studies of this fauna - extending the
      ability to identify these species from all life stages and even fragmentary
      remains, setting the stage for a better understanding of interactions among
      species, calibrating the estimations about species composition and richness in an
      ecosystem, and providing tools for authenticating bioproducts and monitoring
      illegal species exploitation.

PMID- 22958718
TI  - Usefulness of diffusion-weighted magnetic resonance imaging in the diagnosis of
      prostate cancer.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the diagnostic
      accuracy of diffusion-weighted magnetic resonance imaging (DWI) in prostate
      cancer. MATERIALS AND METHODS: The MEDLINE, Embase, CANCERLIT, and Cochrane
      Library databases were searched for studies published from January 2001 to August
      2011 evaluating the diagnostic performance of DWI in detecting prostate
      carcinoma. Sensitivities and specificities were determined across studies, and
      summary receiver-operating characteristic curves were constructed using
      hierarchical regression models. RESULTS: Sixteen studies (18 subsets) with a
      total of 852 patients were included. Six studies (seven subsets) examining men
      with pathologically confirmed prostate cancer (260 patients) had pooled
      sensitivity and specificity of 0.88 (95% confidence interval [CI], 0.76-0.95) and
      0.84 (95% CI, 0.76-0.90), respectively. Compared to patients at high risk for
      clinically relevant cancer, sensitivity was higher in low-risk patients (0.94
      [95% CI, 0.89-0.97] vs 0.62 [95% CI, 0.54-0.70], P < .05), but specificity was
      lower (0.86 [95% CI, 0.72-0.94] vs 0.89 [95% CI, 0.83-0.93], P < .05). Ten
      studies (11 subsets) examining patients with suspected prostate cancer (592
      patients) had pooled sensitivity and specificity of 0.76 (95% CI, 0.68-0.84) and
      0.86 (95% CI, 0.79-0.91). Sensitivity was lower in high-risk patients (0.74 [95%
      CI, 0.57-0.87] vs 0.78 [95% CI, 0.70-0.84], P > .05), but specificity was higher
      (0.92 [95% CI, 0.89-0.94] vs 0.78 [95% CI, 0.70-0.84], P < .05). CONCLUSIONS: A
      limited number of small studies suggest that DWI could be a rule-in test for high
      risk patients. Further prospective studies including larger populations are
      necessary to confirm the actual value of DWI in this field.

PMID- 22958719
TI  - Automated texture-based quantification of centrilobular nodularity and
      centrilobular emphysema in chest CT images.
AB  - RATIONALE AND OBJECTIVES: Characterization of smoking-related lung disease
      typically consists of visual assessment of chest computed tomographic (CT) images
      for the presence and extent of emphysema and centrilobular nodularity (CN).
      Quantitative analysis of emphysema and CN may improve the accuracy,
      reproducibility, and efficiency of chest CT scoring. The purpose of this study
      was to develop a fully automated texture-based system for the detection and
      quantification of centrilobular emphysema (CLE) and CN in chest CT images.
      MATERIALS AND METHODS: A novel approach was used to prepare regions of interest
      (ROIs) within the lung parenchyma for representation by texture features
      associated with the gray-level run-length and gray-level gap-length methods.
      These texture features were used to train a multiple logistic regression
      classifier to discriminate between normal lung tissue, CN or "smoker's lung," and
      CLE. This classifier was trained and evaluated on 24 and 71 chest CT scans,
      respectively. RESULTS: During training, the classifier correctly classified 89%
      of ROIs depicting normal lung tissue, 74% of ROIs depicting CN, and 95% of ROIs
      manifesting CLE. When the performance of the classifier in quantifying extent of
      CN and CLE was evaluated on 71 chest CT scans, 65% of ROIs in smokers without CLE
      were classified as CN, compared to 31% in nonsmokers (P < .001) and 28% in
      smokers with CLE (P < .001). CONCLUSIONS: The texture-based framework described
      herein facilitates successful discrimination among normal lung tissue, CN, and
      CLE and can be used for the automated quantification of smoking-related lung
      disease.

PMID- 22958721
TI  - Retail venue based screening mammography: assessment of women's preferences.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to explore women's interest
      and preferences in undergoing screening mammography in a retail health care
      setting. MATERIALS AND METHODS: Self-administered surveys were distributed to 400
      mammography patients in May to June 2009. All of the women who were asked were
      eligible for screening (age >40 years, no abnormal mammographic findings in the
      recent past). Three hundred eighty-six screening-eligible women filled out and
      returned the self-administered survey. RESULTS: The average respondent age was 57
      years. Three hundred ten of the patients (80.3%) had college or postgraduate
      educations. Two hundred three (52.6%) reported annual incomes >$60,000. Two
      hundred forty-one respondents (62.4%) had been undergoing screening mammography
      for >10 years, while this was the first examination for eight patients (2%). More
      than half of the patients (n = 215 [55.7%]) affirmed their interest in undergoing
      annual screening mammography in a private area within a retail shopping facility.
      Most preferred a pharmacy (77%) over Wal-Mart or a grocery store. Appealing
      factors about a retail setting were proximity to home (90%), free parking (62%),
      and operating hours (48.8%). CONCLUSIONS: There is interest among women in
      undergoing screening mammography at retail health care clinics, preferably
      pharmacies. The provision of services at a convenient location can increase
      adherence to guidelines for screening mammography.

PMID- 22958722
TI  - Osteoporosis screening using areal bone mineral density estimation from
      diagnostic CT images.
AB  - RATIONALE AND OBJECTIVES: A reliable and cost-effective method for osteoporosis
      screening is important in addressing the increase in osteoporotic fractures due
      to aging populations. Diagnostic computed tomographic (dCT) images may contain
      densitometric information useful for osteoporosis screening. The aim of this
      study was to investigate the relationship between areal bone mineral density
      (aBMD) and volumetric information on dCT imaging and its suitability for building
      an osteopenia screening system. The goal of this system is to estimate aBMD and
      predict bone disease condition on the basis of dCT images of the lumbar spine.
      MATERIALS AND METHODS: Dual-energy x-ray absorptiometry (DXA) aBMD and computed
      tomographic (CT) images were obtained from 44 male patients (mean age, 60 years).
      An aBMD from CT images (aBMD(CT)) was computed from the CT volume using
      established relationships of Hounsfield units to bone density and used to
      estimate DXA-derived aBMD (aBMD(DxA)). Estimated aBMD(CT) was then applied to
      diagnose osteopenia of the lumbar spine using statistical methods. RESULTS: For
      the estimation of aBMD(DxA) from aBMD(CT), the proposed approach yielded a high
      correlation factor of r = 0.852, with a root mean square error of 0.0884 g/cm(2).
      The correlation was strongest when every slice in the dCT volume and both
      trabecular and cortical bone components were used. The classifier achieved an
      overall classification accuracy of 80.1% and an area under the receiver-operating
      characteristic curve of 0.894. CONCLUSIONS: This clinical study demonstrates that
      aBMD(DxA) can be determined from routine CT data. Estimated aBMD(DxA) can be
      extended to form a dCT imaging-based opportunistic screening system for the
      detection and management of osteopenia.

PMID- 22958720
TI  - When and why might a computer-aided detection (CAD) system interfere with visual
      search? An eye-tracking study.
AB  - RATIONAL AND OBJECTIVES: Computer-aided detection (CAD) systems are intended to
      improve performance. This study investigates how CAD might actually interfere
      with a visual search task. This is a laboratory study with implications for
      clinical use of CAD. METHODS: Forty-seven naive observers in two studies were
      asked to search for a target, embedded in 1/f(2.4) noise while we monitored their
      eye movements. For some observers, a CAD system marked 75% of targets and 10% of
      distractors, whereas other observers completed the study without CAD. In
      experiment 1, the CAD system's primary function was to tell observers where the
      target might be. In experiment 2, CAD provided information about target identity.
      RESULTS: In experiment 1, there was a significant enhancement of observer
      sensitivity in the presence of CAD (t(22) = 4.74, P < .001), but there was also a
      substantial cost. Targets that were not marked by the CAD system were missed more
      frequently than equivalent targets in no-CAD blocks of the experiment (t(22) =
      7.02, P < .001). Experiment 2 showed no behavioral benefit from CAD, but also no
      significant cost on sensitivity to unmarked targets (t(22) = 0.6, P = NS).
      Finally, in both experiments, CAD produced reliable changes in eye movements: CAD
      observers examined a lower total percentage of the search area than the no-CAD
      observers (experiment 1: t(48) = 3.05, P < .005; experiment 2: t(50) = 7.31, P <
      .001). CONCLUSIONS: CAD signals do not combine with observers' unaided
      performance in a straightforward manner. CAD can engender a sense of certainty
      that can lead to incomplete search and elevated chances of missing unmarked
      stimuli.

PMID- 22958723
TI  - Radiology's role in the battle against pediatric cancers.

PMID- 22958724
TI  - History of radiology.

PMID- 22958725
TI  - Antibiotic resistance patterns and extended-spectrum beta-lactamase production
      among Acinetobacter spp. isolated from an intensive care Unit of a hospital in
      Kerman, Iran.
AB  - BACKGROUND: The global increase in multidrug resistance of Acinetobacter spp.
      has created widespread problems in the treatment of patients in intensive care
      units (ICUs) of hospitals. To assess the sensitivity of Acinetobacter isolates to
      antibiotics routinely used in ICUs, we investigated antibiotic resistance
      patterns and extended-spectrum beta-lactamase (ESBL) production among
      Acinetobacter spp. isolated from the ICU of a university hospital in Kerman,
      Iran. METHODS: Fifteen isolates of Acinetobacter spp. were recovered from one
      hundred clinical specimens collected from the ICU of Afzalipoor Hospital in
      Kerman, Iran, from October 2010 to June 2011. Preliminary antibiotic sensitivity
      testing was carried out using the disk-diffusion breakpoint assay, and MICs of
      different antibiotics were determined using the E-test. ESBL production was
      detected by a double-disk synergy test and confirmed by a phenotypic confirmatory
      test. Substrate hydrolysis in the presence and absence of the following
      inhibitors was carried out using the rapid fixed-time method: para
      chloromercuribenzoate (p-CMB), clavulanic acid, sulbactam, and NaCl. RESULTS:
      Overall, 73.3% of the isolates were resistant to imipenem (MIC range 240-128
      ug/mL) and 66% to ciprofloxacin (MIC range 240-64 +/- 0.08 ug/mL). All of the
      isolates were fully resistant (MIC 240 ug/mL) to piperacillin, while 93.3%,
      53.3%, and 93.3% were resistant to piperacillin + tazobactam (MIC 240 ug/mL),
      amikacin (MIC range 128-16 ug/mL), and cefepime (MIC range 240-60 ug/mL),
      respectively. The isolates were also resistant to chloramphenicol and
      tetracycline: MICs of these two agents were >= 240 ug/mL. The test for ESBL
      production was positive for only three isolates (nos. 1, 10, and 15). The rate of
      substrate hydrolysis was highest in the presence of p-CMB (80.2 +/- 0.02) and
      lowest in the presence of NaCl (2.1 +/- 0.01) (P <= 0.05). CONCLUSIONS: Many
      isolates of Acinetobacter spp. are resistant to almost all antibiotics routinely
      used in the ICU of our hospital, including imipenem, ciprofloxacin, and
      piperacillin + tazobactam. Three isolates were ESBL producers. The other isolates
      exhibited high resistance to beta-lactams, but they did not produce any ESBL
      enzymes.

PMID- 22958727
TI  - Effect of radiological extent and severity of bronchiectasis on pulmonary
      function.
AB  - BACKGROUND: The aim of this study was to ascertain the effect of the extent and
      severity of bronchiectasis as determined with high-resolution computed tomography
      (HRCT) on lung function in patients with pure bronchiectasis, bronchiectasis and
      asthma, and bronchiectasis and chronic obstructive pulmonary disease (COPD).
      METHODS: One hundred nineteen patients (71 with pure bronchiectasis, 25 asthmatic
      patients with bronchiectasis, and 23 COPD patients with bronchiectasis) underwent
      HRCT and pulmonary function tests. Computed tomography features were scored by
      the consensus of 2 radiologists. RESULTS: There were no statistically significant
      differences among the 3 patient groups regarding the extent of bronchiectasis,
      bronchial dilatation degree, bronchial wall thickening, decreased attenuation in
      the lung parenchyma, or presence of mucus in the large and small airways. In the
      pure bronchiectasis group, a negative correlation was found between forced vital
      capacity (FVC) % of predicted, forced expiratory volume in 1 sec (FEV1) % of
      predicted, the FEV1/FVC ratio and the extent of bronchiectasis, bronchial wall
      thickening, bronchial wall dilatation, and decreased attenuation. At multivariate
      analysis the main morphologic changes associated with impairment of FVC and FEV1
      were the extent of bronchiectasis and a decreased attenuation in the lung
      parenchyma. The decrease in the FEV1/FVC ratio was associated with bronchial wall
      dilatation. No correlation was found between morphologic changes and indices of
      pulmonary function in the asthma and COPD patients. CONCLUSIONS: Morphologic
      changes associated with bronchiectasis do not influence lung function in patients
      with asthma and COPD directly, although they do play a role in impairing
      pulmonary function in patients with bronchiectasis alone.

PMID- 22958726
TI  - Oral health status and the epidemiologic paradox within Latino immigrant groups.
AB  - BACKGROUND: According to the United States census, there are 28 categories that
      define "Hispanic/Latinos." This paper compares differences in oral health status
      between Mexican immigrants and other Latino immigrant groups. METHODS: Derived
      from a community-based sample (N = 240) in Los Angeles, this cross-sectional
      study uses an interview covering demographic and behavioral measures, and an
      intraoral examination using NIDCR epidemiologic criteria. Descriptive, bivariate
      analysis, and multiple regression analysis were conducted to examine the
      determinants that are associated with the Oral Health Status Index (OHSI).
      RESULTS: Mexican immigrants had a significantly higher OHSI (p < .05) compared to
      other Latinos. The multilinear regression showed that both age and gender (p <
      .05), percentage of untreated decayed teeth (p < .001), number of replaced
      missing teeth (p < .001), and attachment loss (p < .001) were significant.
      CONCLUSIONS: Compared with the other Latino immigrants in our sample, Mexican
      immigrants have significantly better oral health status. This confirms the
      epidemiologic paradox previously found in comparisons of Mexicans with whites and
      African Americans. In this case of oral health status the paradox also occurs
      between Mexicans and other Latinos. Therefore, when conducting oral health
      studies of Latinos, more consideration needs to be given to differences within
      Latino subgroups, such as their country of origin and their unique ethnic and
      cultural characteristics.

PMID- 22958728
TI  - Imaging of central airway stenting with multidetector computed tomography.

PMID- 22958730
TI  - Delayed anastomosis after ileocolonic resection in high-risk Crohn's disease
      patients.

PMID- 22958729
TI  - Prognostic value of pretreatment and recovery duration of cranial nerve palsy in
      nasopharyngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the prognostic value of
      cranial nerve (CN) palsy in nasopharyngeal carcinoma (NPC) patients. METHODS: A
      retrospective analysis was performed on CN involvement using medical records of
      178 consecutive patients with histologically diagnosed, non-disseminated NPC.
      RESULTS: In 178 NPC patients with CN palsy, the 5-year survival rates were as
      follows: overall survival (OS), 61.0%; disease-specific survival (DSS), 69.6%;
      local relapse-free survival (LRFS), 75.2%; distant metastasis-free survival
      (DMFS), 73.4%; and disease-free survival (DFS), 55.3%. Significant differences
      were observed in the 5-year OS rates between patients with single and multiple CN
      palsy (69.8% vs. 54.3%; P=0.033) and the OS rates between patients with different
      pretreatment durations (68.7% vs. 43.3%, P=0.007). However, no significant
      differences were observed in OS, DSS, LRFS and DFS rates between patients with
      upper and lower CN palsy (P=0.581, P=0.792, P=0.729 and P=0.212, respectively).
      The results showed that recovery duration was an independent prognostic factor
      for OS (HR=2.485; P<0.001), DSS (HR=2.065; P=0.016), LRFS (HR=3.051; P=0.001) and
      DFS (HR=2.440; P<0.001). CONCLUSIONS: Recovery duration is an independent
      prognostic factor for NPC patients with CN palsy and is related to recurrence,
      which leads to poor survival. Recovery duration requires close surveillance and
      different treatment regimens.

PMID- 22958731
TI  - COPD: a model for chronic respiratory disease.

PMID- 22958732
TI  - Fear of falling and associated activity restriction in older people. results of a
      cross-sectional study conducted in a Belgian town.
AB  - OBJECTIVES: This article aims at describing, in a Belgian town, the frequency of
      the fear of falling and of subsequent activity restriction among non
      institutionalised people aged 65 years and over, and at identifying persons
      affected by these two issues. METHODS: Cross-sectional survey conducted in
      Fontaine l'Eveque (Belgium) in 2006, using a self-administered questionnaire.
      RESULTS: The participants could fill in the questionnaire on their own or with
      the help of a third party if needed. The latter were not taken into account in
      this article. Analyses covered 419 questionnaires. Fear of falling and activity
      restriction were reported by, respectively, 59.1% and 33.2% of participants. They
      were more frequent among fallers but also affected non-fallers. In logistic
      regression analyses: gender, the fact of living alone and the number of falls
      were significantly associated with fear of falling; gender, age and the number of
      falls were significantly associated with activity restriction. CONCLUSIONS: Our
      study, despite various limitations, shows the importance of fear of falling and
      of subsequent activity restriction among older people, among fallers as well as
      among non-fallers. It also provides information, though limited, concerning
      persons affected by these two issues in Belgium, and in other contexts as well.
      Given the ageing of our populations, it is important to take these problems into
      account when caring for older people.

PMID- 22958733
TI  - Effect of sex and rearing system on the quality and mineral content of fiber from
      raeini cashmere goats.
AB  - The aim of this study was to compare the quality characteristics and mineral
      content of the fiber from male and female cashmere goats raised under different
      management systems. Male and female Raeini cashmere goats (<1.5 years of age, n =
      48) were selected from flocks raised at a government breeding station or raised
      commercially under either rural or nomadic conditions. The staple length,
      cashmere fiber diameter, coefficient of variation for fiber diameter, percentage
      of cashmere in a fleece, percentage of guard hair in a fleece and cashmere
      tenacity averaged 4.6 +/-0.1 cm, 18.0 +/-0.1 MUm, 20.9 +/- 0.4%, 66.1 +/- 1.5%,
      33.8 +/- 1.5% and 1.8 +/- 0.2 gf/tex, respectively. The sulfur, copper and zinc
      content of the cashmere averaged 2.8 +/- 0.1%, 0.00065 +/- 0.00002% and 0.01276
      +/- 0.00025%, respectively. Rearing method significantly affected staple length,
      coefficient of variation of fiber diameter, cashmere tenacity and copper content.
      Males had a higher coefficient of variation of fiber diameter and cashmere
      tenacity than females (P < 0.05).

PMID- 22958734
TI  - New, puzzling insights from comparative myological studies on the old and
      unsolved forelimb/hindlimb enigma.
AB  - Most textbooks and research reports state that the structures of the tetrapod
      forelimbs and hindlimbs are serial homologues. From this view, the main challenge
      of evolutionary biologists is not to explain the similarity between tetrapod
      limbs, but instead to explain why and how they have diverged. However, these
      statements seem to be related to a confusion between the serial homology of the
      vertebrate pelvic and pectoral appendages as a whole, and the serial homology of
      the specific soft- and hard-tissue structures of the tetrapod forelimbs and
      hindlimbs, leading to an even more crucial and puzzling question being
      overlooked: why are the skeletal and particularly the muscle structures of the
      forelimb and hindlimb actually so strikingly similar to each other? Herein we
      provide an updated discussion of these questions and test two main hypotheses:
      (i) that the similarity of the limb muscles is due to serial homology; and (ii)
      that tetrapods that use hindlimbs for a largely exclusive function (e.g.
      bipedalism in humans) exhibit fewer cases of similarity between forelimbs and
      hindlimbs than do quadrupedal species. Our review shows that of the 23 arm,
      forearm and hand muscles/muscle groups of salamanders, 18 (78%) have clear
      'topological equivalents' in the hindlimb; in lizards, 14/24 (58%); in rats,
      14/35 (40%); and in modern humans, 19/37 (51%). These numbers seem to support the
      idea that there is a plesiomorphic similarity and subsequent evolutionary
      divergence, but this tendency actually only applies to the three former
      quadrupedal taxa. Moreover, if one takes into account the total number of
      'correspondences', one comes to a surprising and puzzling conclusion: in modern
      humans the number of forelimb muscles/muscle groups with clear 'equivalents' in
      the hindlimb (19) is substantially higher than in quadrupedal mammals such as
      rats (14), lizards (14) and even salamanders (18). These data contradict the
      hypothesis that divergent functions lead to divergent morphological structures.
      Furthermore, as we show that at least five of the 19 modern human adult forelimb
      elements that have a clear hindlimb 'equivalent' derive from embryonic anlages
      that are very different from the ones giving rise to their adult hindlimb
      'equivalents', they also contradict the hypothesis that the similarity in muscle
      structures between the forelimb and hindlimb of tetrapods such as modern humans
      are due to their origin as serial homologues. This similarity is instead the
      result of phylogenetically independent evolutionary changes leading to a
      parallelism/convergence due to: (i) developmental constraints, i.e. similar
      molecular mechanisms are involved (particularly in the formation of the
      neomorphic hand), but this does not necessarily mean that similar anlages are
      used to form the similar adult structures; (ii) functional constraints, related
      to similar adaptations; (iii) topological constraints, i.e. limited physical
      possibilities; and even (iv) phylogenetic constraints, which tend to
      prevent/decrease the occurrence of new homoplasic similarities, but also help to
      keep older, ancestral homoplasic resemblances.

PMID- 22958735
TI  - Modeling overdispersed longitudinal binary data using a combined beta and normal
      random-effects model.
AB  - BACKGROUND: In medical and biomedical areas, binary and binomial outcomes are
      very common. Such data are often collected longitudinally from a given subject
      repeatedly overtime, which result in clustering of the observations within
      subjects, leading to correlation, on the one hand. The repeated binary outcomes
      from a given subject, on the other hand, constitute a binomial outcome, where the
      prescribed mean-variance relationship is often violated, leading to the so-called
      overdispersion. METHODS: Two longitudinal binary data sets, collected in south
      western Ethiopia: the Jimma infant growth study, where the child's early growth
      is studied, and the Jimma longitudinal family survey of youth where the
      adolescent's school attendance is studied over time, are considered. A new model
      which combines both overdispersion, and correlation simultaneously, also known as
      the combined model is applied. In addition, the commonly used methods for binary
      and binomial data, such as the simple logistic, which accounts neither for the
      overdispersion nor the correlation, the beta-binomial model, and the logistic
      normal model, which accommodate only for the overdispersion, and correlation,
      respectively, are also considered for comparison purpose. As an alternative
      estimation technique, a Bayesian implementation of the combined model is also
      presented. RESULTS: The combined model results in model improvement in fit, and
      hence the preferred one, based on likelihood comparison, and DIC criterion.
      Further, the two estimation approaches result in fairly similar parameter
      estimates and inferences in both of our case studies. Early initiation of
      breastfeeding has a protective effect against the risk of overweight in late
      infancy (p = 0.001), while proportion of overweight seems to be invariant among
      males and females overtime (p = 0.66). Gender is significantly associated with
      school attendance, where girls have a lower rate of attendance (p = 0.001) as
      compared to boys. CONCLUSION: We applied a flexible modeling framework to analyze
      binary and binomial longitudinal data. Instead of accounting for overdispersion,
      and correlation separately, both can be accommodated simultaneously, by allowing
      two separate sets of the beta, and the normal random effects at once.

PMID- 22958736
TI  - Effects of hospital delivery during off-hours on perinatal outcome in several
      subgroups: a retrospective cohort study.
AB  - BACKGROUND: Studies have demonstrated a higher risk of adverse outcomes among
      infants born or admitted during off-hours, as compared to office hours, leading
      to questions about quality of care provide during off-hours (weekend, evening or
      night). We aim to determine the relationship between off-hours delivery and
      adverse perinatal outcomes for subgroups of hospital births. METHODS: This
      retrospective cohort study was based on data from the Netherlands Perinatal
      Registry, a countrywide registry that covers 99% of all hospital births in the
      Netherlands. Data of 449,714 infants, born at 28 completed weeks or later, in the
      period 2003 through 2007 were used. Infants with a high a priori risk of
      morbidity or mortality were excluded. Outcome measures were intrapartum and early
      neonatal mortality, a low Apgar score (5 minute score of 0-6), and a composite
      adverse perinatal outcome measure (mortality, low Apgar score, severe birth
      trauma, admission to a neonatal intensive care unit). RESULTS: Evening and night
      time deliveries that involved induction or augmentation of labour, or an
      emergency caesarean section, were associated with an increased risk of an adverse
      perinatal outcome when compared to similar daytime deliveries. Weekend deliveries
      were not associated with an increased risk when compared to weekday deliveries.
      It was estimated that each year, between 126 and 141 cases with an adverse
      perinatal outcomes could be attributed to this evening and night effect. Of
      these, 21 (15-16%) are intrapartum or early neonatal death. Among the 3100
      infants in the study population who experience an adverse outcome each year,
      death accounted for only 5% (165) of these outcomes. CONCLUSION: This study shows
      that for infants whose mothers require obstetric interventions during labour and
      delivery, birth in the evening or at night, are at an increased risk of an
      adverse perinatal outcomes.

PMID- 22958737
TI  - Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of
      the literature.
AB  - Methotrexate (MTX) is a folate-antagonist used in several neoplastic and
      inflammatory diseases. Reports of pulmonary complications in patients given low
      dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable
      frequency and can present with different forms. Most often MTX-induced pneumonia
      in patients affected by rheumatoid arthritis (RA) is reported.In this paper we
      describe a case of MTX-related pneumonitis in a relatively young woman affected
      by Crohn's disease who presented non-productive cough, fever and dyspnea on
      exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at
      computed tomography (CT) ground-glass opacities appeared in both lungs. At
      spirometry an obstructive defect was demonstrated. A rapid improvement of
      symptoms and the regression of radiographic and spirometric alterations was
      achieved through MTX withdrawal and the introduction of corticosteroid therapy.

PMID- 22958738
TI  - Virtual histology assessment of cardiac allograft vasculopathy following
      introduction of everolimus--results of a multicenter trial.
AB  - In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant
      (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor
      (CNI) exposure or continued standard CNI-therapy underwent matched virtual
      histology (VH) examination to evaluate morphological progression of cardiac
      allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory
      markers was also performed. A similar rate of quantitative CAV progression was
      observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index
      1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis
      revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p =
      0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among
      everolimus patients compared to controls. The increase in necrotic and calcified
      components was most prominent in everolimus patients with time since HTx >5.1
      years and was accompanied by a significant increase in levels of von Willebrand
      (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03).
      Conversion to everolimus and reduced CNI is associated with a significant
      increase in calcified and necrotic intimal components and is more prominent in
      patients with a longer time since HTx. A significant increase in vWF and VCAM
      accompanied these qualitative changes and the prognostic implication of these
      findings requires further investigation.

PMID- 22958740
TI  - Chitin membranes containing silver nanoparticles for wound dressing application.
AB  - Silver nanoparticles are gaining importance as an antimicrobial agent in wound
      dressings. Chitin is a biopolymer envisioned to promote rapid dermal regeneration
      and accelerate wound healing. This study was focused on the evaluation of chitin
      membranes containing silver nanoparticles for use as an antimicrobial wound
      dressing. Silver nanoparticles were synthesised by gamma irradiation at doses of
      50 kGy in the presence of sodium alginate as stabiliser. The UV-Vis absorption
      spectra of nanoparticles exhibited an absorption band at 415-420 nm, which is the
      typical plasmon resonance band of silver nanoparticles. The peaks in the X-ray
      diffraction (XRD) pattern are in agreement with the standard values of the face
      centred cubic silver. Transmission electron microscopy (TEM) images indicate
      silver nanoparticles with spherical morphology and small particle size in the
      range of 3-13 nm. In vitro antimicrobial tests were performed using Pseudomonas
      aeruginosa and Staphylococcus aureus to determine the antimicrobial efficiency of
      the chitin membranes containing 30, 50, 70 and 100 ppm nanosilver. No viable
      counts for P. aeruginosa were detected with 70 ppm silver nanoparticles dressing
      after 1-hour exposure. A 2-log reduction in viable cell count was observed for S.
      aureus after 1 hour and a 4-log reduction after 6 hours with 100 ppm nanosilver
      chitin membranes. This study demonstrates the antimicrobial capability of chitin
      membranes containing silver nanoparticles. The chitin membranes with 100 ppm
      nanosilver showed promising antimicrobial activity against common wound
      pathogens. 

PMID- 22958739
TI  - Proteomic analysis reveals resistance mechanism against biofuel hexane in
      Synechocystis sp. PCC 6803.
AB  - BACKGROUND: Recent studies have demonstrated that photosynthetic cyanobacteria
      could be an excellent cell factory to produce renewable biofuels and chemicals
      due to their capability to utilize solar energy and CO2 as the sole energy and
      carbon sources. Biosynthesis of carbon-neutral biofuel alkanes with good chemical
      and physical properties has been proposed. However, to make the process
      economically feasible, one major hurdle to improve the low cell tolerance to
      alkanes needed to be overcome. RESULTS: Towards the goal to develop robust and
      high-alkane-tolerant hosts, in this study, the responses of model cyanobacterial
      Synechocystis PCC 6803 to hexane, a representative of alkane, were investigated
      using a quantitative proteomics approach with iTRAQ - LC-MS/MS technologies. In
      total, 1,492 unique proteins were identified, representing about 42% of all
      predicted protein in the Synechocystis genome. Among all proteins identified, a
      total of 164 and 77 proteins were found up- and down-regulated, respectively.
      Functional annotation and KEGG pathway enrichment analyses showed that common
      stress responses were induced by hexane in Synechocystis. Notably, a large number
      of transporters and membrane-bound proteins, proteins against oxidative stress
      and proteins related to sulfur relay system and photosynthesis were induced,
      suggesting that they are possibly the major protection mechanisms against hexane
      toxicity. CONCLUSION: The study provided the first comprehensive view of the
      complicated molecular mechanism employed by cyanobacterial model species,
      Synechocystis to defend against hexane stress. The study also provided a list of
      potential targets to engineer Synechocystis against hexane stress.

PMID- 22958741
TI  - Efficacy of minimally invasive therapies on unresectable pancreatic cancer.
AB  - For patients with unresectable pancreatic cancer, current chemotherapies have
      negligible survival benefits. Thus, developing effective minimally invasive
      therapies is currently underway. This study was conducted to evaluate the
      efficacy of transarterial chemoembolization plus radiofrequency ablation and/or
      125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed
      the outcome of 71 patients with unresectable pancreatic carcinoma who underwent
      chemoembolization plus radiofrequency ablation and/or radioactive seed
      implantation. Of the 71 patients, the median survival was 11 months, and the 1-,
      2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6%, respectively.
      Patients who had no metastasis, who had oligonodular liver metastases (<=3
      lesions), and who had multinodular liver metastases (>3 lesions) had median
      survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates
      of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients
      without liver metastases was worse than that of patients with oligonodular liver
      metastasis, the result was not significant (P = 0.239). In contrast, the
      metastasis-negative patients had significantly better survival than did patients
      with multinodular liver metastases (P < 0.001). Patients with oligonodular liver
      lesions had a significant longer median survival than did patients with
      multinodular lesions (P < 0.001). In conclusion, combined minimally invasive
      therapies had good efficacy on unresectable pancreatic cancer and resulted in a
      good control of liver metastases. In addition, the number of liver metastases was
      a significant factor in predicting prognosis and response to treatment.

PMID- 22958742
TI  - Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial
      neoplasia and cervical cancer.
AB  - The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely
      known to play a biologically relevant role in tumor growth and spread. Recent
      evidence suggests that CXCL16, a novel chemokine, is overexpressed in
      inflammation-associated tumors and mediates pro-tumorigenic effects of
      inflammation in prostate cancer. We therefore analyzed the expression of CXCL12
      and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical
      intraepithelial neoplasia (CIN) and cervical cancer and further assessed their
      association with clinicopathologic features and outcomes. Tissue chip technology
      and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4,
      CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and
      cervical carcinoma (60 cases). The association of protein expression with
      clinicopathologic features and overall survival was analyzed. These four proteins
      were clearly detected in membrane and cytoplasm of neoplastic epithelial cells,
      and their distribution and intensity of expression increased as neoplastic
      lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore,
      the expression of CXCR4 was associated significantly with the histologic grade of
      cervical carcinoma, whereas the expression of CXCR6 was associated significantly
      with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6
      expression had significantly shorter overall survival than did those with low
      CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and
      CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical
      carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a
      valuable prognostic factor for cervical cancer.

PMID- 22958743
TI  - Retroperitoneal schwannoma mimicking metastatic seminoma: case report and
      literature review.
AB  - If a testicular cancer patient has a mass in the retroperitoneum, a metastasis is
      often the first suspicion, probably leading to improper diagnosis and
      overtreatment. Here we report a case of retroperitoneal schwannoma mimicking
      metastatic seminoma. A 29-year-old man, who had a history of seminoma, presented
      with a single retroperitoneal mass suspected to be a metastasis. Because the
      patient refused radiotherapy, 3 cycles of cisplatin, etoposide, and bleomycin
      were offered. Post-chemotherapy computed tomography scan revealed persistence of
      the retroperitoneal mass, with no change in tumor size or characteristics.
      Subsequently, retroperitoneal lymph node dissection was performed. The dissected
      tissue contained negative lymph nodes but a single mass in the attached fat.
      Pathology revealed retroperitoneal schwannoma, which was confirmed by
      immunohistochemistry. Thus, clinicians should be aware of retroperitoneal
      schwannoma and its distinction from metastatic seminoma to avoid misdiagnosis and
      ensure proper treatment.

PMID- 22958745
TI  - Spontaneous pneumothorax.

PMID- 22958746
TI  - Decreasing healthcare-associated infections (HAI) is an efficient method to
      decrease healthcare-associated Methicillin-resistant S.aureus (MRSA) infections
      Antimicrobial resistance data from the German national nosocomial surveillance
      system KISS.
AB  - BACKGROUND: By analysing the data of the intensive care unit (ICU) component of
      the German national nosocomial infection surveillance system (KISS) during the
      last ten years, we have observed a steady increase in the MRSA rates
      (proportions) from 2001 to 2005 and only a slight decrease from 2006 to 2010. The
      objective of this study was to investigate the development of the incidence
      density of nosocomial MRSA infections because this is the crucial outcome for
      patients. FINDINGS: Data from 103 ICUs with ongoing participation during the
      observation period were included. The pooled incidence density of nosocomial MRSA
      infections decreased significantly from 0.37 per 1000 patient days in 2001 to
      0.15 per 1000 patient days in 2010 (RR = 0.40; CI95 0.29-0.55). This decrease was
      proportional to the significant decrease of all HCAI during the same time period
      (RR = 0.61; CI95 0.58-0.65). CONCLUSIONS: The results underline the need to
      concentrate infection control activities on measures to control HCAI in general
      rather than focusing too much on specific MRSA prevention measures. MRSA rates
      (proportions) are not a very useful indicator of the situation.

PMID- 22958747
TI  - Toxicity of oxidized phospholipids in cultured macrophages.
AB  - BACKGROUND: The interactions of oxidized low-density lipoprotein (LDL) and
      macrophages are hallmarks in the development of atherosclerosis. The biological
      activities of the modified particle in these cells are due to the content of
      lipid oxidation products and apolipoprotein modification by oxidized
      phospholipids. RESULTS: It was the aim of this study to determine the role of
      short-chain oxidized phospholipids as components of modified LDL in cultured
      macrophages. For this purpose we investigated the effects of the following
      oxidized phospholipids on cell viability and apoptosis: 1-palmitoyl-2-glutaroyl
      sn-glycero-3-phosphocholine (PGPC), 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3
      phosphocholine (POVPC) and oxidized alkylacyl phospholipids including 1-O
      hexadecyl-2-glutaroyl-sn-glycero-3-phosphocholine (E-PGPC) and 1-O-hexadecyl-2-(5
      oxovaleroyl)-sn-glycero-3-phosphocholine (E-POVPC). We found that these compounds
      induced apoptosis in RAW264.7 and bone marrow-derived macrophages. The sn-2
      carboxyacyl lipid PGPC was more toxic than POVPC which carries a reactive
      aldehyde function in position sn-2 of glycerol. The alkylacyl phospholipids (E
      PGPC and E-POVPC) and the respective diacyl analogs show similar activities.
      Apoptosis induced by POVPC and its alkylether derivative could be causally linked
      to the fast activation of an acid sphingomyelinase, generating the apoptotic
      second messenger ceramide. In contrast, PGPC and its ether analog only negligibly
      affected this enzyme pointing to an entirely different mechanism of lipid
      toxicity. The higher toxicity of PGPC is underscored by more efficient membrane
      blebbing from apoptotic cells. In addition, the protein pattern of PGPC-induced
      microparticles is different from the vesicles generated by POPVC. CONCLUSIONS: In
      summary, our data reveal that oxidized phospholipids induce apoptosis in cultured
      macrophages. The mechanism of lipid toxicity, however, largely depends on the
      structural features of the oxidized sn-2 chain.

PMID- 22958749
TI  - Vitamin D: a clinical perspective.
AB  - Vitamin D has been the focus of considerable recent scientific study and media
      attention because of a growing appreciation of its potential importance in extra
      skeletal health. This 'Perspective' presents data supporting the viewpoint that
      physicians should not routinely test vitamin D levels in the general population
      but should routinely endorse vitamin D supplementation at levels recommended by
      the Institute of Medicine. It further reasons that it is unadvisable to recommend
      intentional limited sun exposure as a source of vitamin D.

PMID- 22958748
TI  - Association between salivary pH and metabolic syndrome in women: a cross
      sectional study.
AB  - BACKGROUND: The salivary flow rate is an important determinant of salivary pH. It
      is influenced by several metabolic syndrome (MetS) components as well as the
      menopausal status. The cluster of cardiometabolic risk factors that characterizes
      the MetS could be exacerbated following menopause. The objective of this study
      was therefore to document the association between salivary pH and MetS expression
      in women according to the menopausal status. METHODS: In this cross-sectional
      study, unstimulated saliva collection was performed on 198 Caucasian women of
      French-Canadian origin of which 55 were premenopausal women (PMW) and 143
      menopausal women (MW). Student's t test, ANOVA and correlation analyses were used
      to assess the association between salivary pH and MetS components. RESULTS: The
      salivary pH level was significantly correlated with several MetS covariates,
      namely triglycerides (TG), apolipoprotein B (apo B) and plasma glucose
      concentrations as well as waist circumference and the number of MetS components
      present in the whole sample and PMW only. Mean pH levels decreased as the number
      of MetS components increased (p = 0.004). The correlations between salivary pH
      and variables associated with MetS components tended to be stronger in PMW. The
      proportion of the variance (R2) of salivary pH explained by MetS-related
      variables in PMW, MW and the whole sample was 23.6% (p = 0.041), 18.1% and 17.0%
      (p < 0.001) respectively. CONCLUSIONS: The increasing prevalence of obesity calls
      for the development of new technologies to more easily monitor health status
      without increasing the burden of healthcare costs. As such, the salivary pH could
      be an inexpensive screening tool. These exploratory data suggest that salivary pH
      may be a significant correlate of the expression of MetS components. However,
      other studies with different populations are needed to confirm these findings
      before our observations lead to practical use in clinical settings.

PMID- 22958750
TI  - Age and immunocompromised status in acute diverticulitis.

PMID- 22958751
TI  - Rationale and clinical benefits of an intensive long-term pulmonary
      rehabilitation program after oesophagectomy: preliminary report.
AB  - Patients who undergo oesophagectomy for oesophagealcancer (OC) usually have an
      overall poor prognosis and, still more preoccupying, an unsatisfactory quality of
      life (QoL). Considering that, as already noted, post-operative pulmonary function
      has a strong correlation with the long-term outcome and QoL after surgery, we
      have assumed and speculated on the clinical benefits of an intensive long-term
      pulmonary post-operative rehabilitation program in this particular subset of
      patients.Herein, we report the preliminary results of a comparative retrospective
      analysis in a series of 58 patients who underwent radical oesophagectomy and post
      operative chest physical therapy (CPT) under two different protocols, from
      October 2006 to January 2011.Finally, we discuss on the time-trend analysis of
      pulmonary function and the potential role of post-operative pulmonary
      rehabilitation.

PMID- 22958752
TI  - Sodium reduction and the correction of iodine intake in Belgium: Policy options.
AB  - Many studies suggest that high salt intakes are related to high blood pressure
      and consequently cardiovascular diseases. In addition salt intake was found to be
      related with obesity, renal stones, osteoporosis and stomach cancer. Belgium,
      such as other European countries, is suffering from both salt intakes that are
      twice as high as the recommended intakes and mild iodine deficiency. No
      comprehensive strategy encompassing both public health problems has been
      developed. While specific salt reduction targets for processed foods are still
      under discussion using a consensus approach with industry, an agreement was
      signed between the bakery sector and the Ministry of Health in April 2009, to
      encourage and increase the use of iodised salt in the production of bread. Based
      on results of recent surveys on population iodine status it is advised not to
      currently revise iodine concentrations in salt in bread but to advocate for a
      higher percentage of bakers using iodised salt and to install a good monitoring
      system to control the percentage of bakers effectively using adequately iodised
      salt. With regard to salt reduction, it is of utmost importance that all
      companies contribute and harmonise the salt content of their products according
      to the lowest possible thresholds in a first step. In order to achieve this goal,
      it will be necessary, in addition to the consensus approach, to come up with at
      least some legislative tools such as a salt tax or mandatory labelling of foods
      exceeding a specific sodium concentration. Once salt reduction targets have been
      clearly defined in Belgium over the longer term, a legal framework should be set
      in place where iodine concentration in salt for the production of bread and
      household salt is strictly regulated by law, to avoid a large variability in the
      iodine content of salt brands consumed. In conclusion, it is possible to tackle
      salt reduction and iodine deficiency at the same time on the condition that the
      approach is coordinated and well monitored. All the interventions and measures
      taken should clearly include education and communication directed towards
      consumers, food producers, public health professionals, pharmacists, healthcare
      workers, and media representatives.

PMID- 22958753
TI  - Effects of novel vaccines on weight loss in diet-induced-obese (DIO) mice.
AB  - The purpose of the study was to test the therapeutic effects of novel vaccines
      for reducing weight gain and increasing weight loss in diet induced obesity (DIO)
      model. Male C57BL/6 J mice, fed a 60% Kcal fat diet for 8 weeks prior to the
      start of the study, were vaccinated via the intraperitoneal route with two
      formulations (JH17 & JH18) of chimeric-somatostatin vaccines at 1 and 22 days of
      the study. Control mice were injected with PBS. All mice continued to be feed the
      60% Kcal fat diet for the 6 week study. Body weights were measured two times a
      week and food intake was measured weekly. At week 6, mice were euthanized and a
      terminal bleed was made and antibody levels to somatostatin and levels of insulin
      like growth factor 1 (IGF-1) were determined. Vaccination with both vaccine
      formulations induced a statistically significant body weight change over the
      study period, as compared with PBS controls. Percentage of baseline body weight
      was also significantly affected by vaccination during the study period.
      Vaccinates finished the study at 104% and 107% of baseline weight, JH17 & JH18
      respectively, while untreated controls reached 115% of baseline weight. Food
      intake per mouse was similar in all mouse groups during the entire study. Control
      mice did not demonstrate any antibody titers to somatostatin, while all
      vaccinated mice had measurable antibody responses (> 1:500,000 titer). IGF-1
      levels were not statistically significant among the groups, but were elevated in
      the JH18 vaccinates (mean 440.4 ng/mL) when compared with PBS controls (mean
      365.6 ng/mL). Vaccination with either JH17 or JH18 chimeric -somatostatin
      vaccines produced a statistically significant weight loss as compared with PBS
      controls (P < 0.0001), even though the DIO mice with continually fed a 60% Kcal
      fat diet. The weight loss/lower weight gain observations were even more
      significant, as all mice consumed similar amounts of food for the entire study.
      The presence of high levels of anti-somatostatin antibodies at 6 weeks was
      correlative with the weight observations and confirmed the success of
      vaccination.

PMID- 22958754
TI  - At home with pulmonary rehabilitation.

PMID- 22958755
TI  - Regulation of ripening and opportunities for control in tomato and other fruits.
AB  - Fruits are an important part of a healthy diet. They provide essential vitamins
      and minerals, and their consumption is associated with a reduced risk of heart
      disease and certain cancers. These important plant products can, however, be
      expensive to purchase, may be of disappointing quality and often have a short
      shelf life. A major challenge for crop improvement in fleshy fruit species is the
      enhancement of their health-promoting attributes while improving quality and
      reducing postharvest waste. To achieve these aims, a sound mechanistic
      understanding of the processes involved in fruit development and ripening is
      needed. In recent years, substantial insights have been made into the mechanistic
      basis of ethylene biosynthesis, perception and signalling and the identity of
      master regulators of ripening that operate upstream of, or in concert with a
      regulatory pathway mediated by this plant hormone. The role of other plant
      hormones in the ripening process has, however, remained elusive, and the links
      between regulators and downstream processes are still poorly understood. In this
      review, we focus on tomato as a model for fleshy fruit and provide an overview of
      the molecular circuits known to be involved in ripening, especially those
      controlling pigment accumulation and texture changes. We then discuss how this
      information can be used to understand ripening in other fleshy fruit-bearing
      species. Recent developments in comparative genomics and systems biology
      approaches are discussed. The potential role of epigenetic changes in generating
      useful variation is highlighted along with opportunities for enhancing the level
      of metabolites that have a beneficial effect on human health.

PMID- 22958756
TI  - Incidence of and socio-biologic risk factors for spontaneous preterm birth in HIV
      positive Nigerian women.
AB  - BACKGROUND: Recent studies have identified HIV as a leading contributor to
      preterm delivery and its associated morbidity and mortality. However little or no
      information exists in our sub-region on this subject. Identifying the factors
      associated with preterm delivery in HIV positive women in our country and sub
      region will not only prevent mother to child transmission of HIV virus but will
      also reduce the morbidity and mortality associated with prematurity and low birth
      weight. This study was designed to determine the incidence and risk factors for
      preterm delivery in HIV positive Nigerians. METHOD: The required data for this
      retrospective study was extracted from the data base of a cohort study of the
      outcome of prevention of mother to child transmission at the Nigerian Institute
      of Medical Research, Lagos. Only data of women that met the eligibility of
      spontaneous delivery after 20 weeks of gestation were included. Ethical approval
      was obtained from the Institution's Ethical Review Board. RESULTS: 181 women out
      of the 1626 eligible for inclusion into the study had spontaneous preterm
      delivery (11.1%). The mean birth weight was 3.1 +/- 0.4 kg, with 10.3% having
      LBW. Spontaneous preterm delivery was found to be significantly associated with
      unmarried status (cOR: 1.7;1.52-2.57), baseline CD4 count <200 cells/mm(3) (cOR:
      1.8; 1.16-2.99), presence of opportunistic infection at delivery (cOR: 2.2;1.23
      3.57), multiple pregnancy (cOR 10.4; 4.24 - 26.17), use of PI based triple ARV
      therapy (eOR 10.2; 5.52 - 18.8) in the first trimester (cOR 2.5; 1.77 - 3.52) on
      univariate analysis. However after multivariate analysis controlling for
      potential confounding variables including low birth weight, only multiple
      pregnancy (aOR: 8.6; CI: 6.73 - 12.9), presence of opportunistic infection at
      delivery (aOR: 1.9; CI: 1.1 - 5.7), and 1st trimester exposure to PI based triple
      therapy (aOR: 5.4; CI: 3.4 - 7.8) retained their significant association with
      preterm delivery. CONCLUSION: The spontaneous preterm delivery rate among our
      cohort was 11.1%. HIV positive women with multiple pregnancies, symptomatic HIV
      infection at delivery and first trimester fetal exposure to PI based triple
      therapy were found to be at risk of spontaneous preterm delivery. Early booking
      and non-use of PI based triple therapy in the first trimester will significantly
      reduce the risk of preterm delivery.

PMID- 22958757
TI  - Nutritional status of school-age children - A scenario of urban slums in India.
AB  - BACKGROUND: One of the greatest problems for India is undernutrition among
      children. The country is still struggling with this problem. Malnutrition, the
      condition resulting from faulty nutrition, weakens the immune system and causes
      significant growth and cognitive delay. Growth assessment is the measurement that
      best defines the health and nutritional status of children, while also providing
      an indirect measurement of well-being for the entire population. METHODS: A cross
      sectional study, in which we explored nutritional status in school-age slum
      children and analyze factors associated with malnutrition with the help of a pre
      designed and pre-tested questionnaire, anthropometric measurements and clinical
      examination from December 2010 to April 2011 in urban slums of Bareilly, Uttar
      Pradesh (UP), India. RESULT: The mean height and weight of boys and girls in the
      study group was lower than the CDC 2000 (Centers for Disease Control and
      Prevention) standards in all age groups. Regarding nutritional status, prevalence
      of stunting and underweight was highest in age group 11 yrs to 13 yrs whereas
      prevalence of wasting was highest in age group 5 yrs to 7 yrs. Except refractive
      errors all illnesses are more common among girls, but this gender difference is
      statistically significant only for anemia and rickets. The risk of malnutrition
      was significantly higher among children living in joint families, children whose
      mother's education was [less than or equal to] 6th standard and children with
      working mothers. CONCLUSIONS: Most of the school-age slum children in our study
      had a poor nutritional status. Interventions such as skills-based nutrition
      education, fortification of food items, effective infection control, training of
      public healthcare workers and delivery of integrated programs are recommended.

PMID- 22958744
TI  - Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and
      genetic syndromes: animal models and clinical findings.
AB  - This review summarizes evidence of dysregulated reward circuitry function in a
      range of neurodevelopmental and psychiatric disorders and genetic syndromes.
      First, the contribution of identifying a core mechanistic process across
      disparate disorders to disease classification is discussed, followed by a review
      of the neurobiology of reward circuitry. We next consider preclinical animal
      models and clinical evidence of reward-pathway dysfunction in a range of
      disorders, including psychiatric disorders (i.e., substance-use disorders,
      affective disorders, eating disorders, and obsessive compulsive disorders),
      neurodevelopmental disorders (i.e., schizophrenia, attention
      deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome,
      conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e.,
      Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome,
      and Rett syndrome). We also provide brief overviews of effective
      psychopharmacologic agents that have an effect on the dopamine system in these
      disorders. This review concludes with methodological considerations for future
      research designed to more clearly probe reward-circuitry dysfunction, with the
      ultimate goal of improved intervention strategies.

PMID- 22958758
TI  - Predictors and outcomes of health-related quality of life in caregivers of
      cardiothoracic transplant recipients.
AB  - Cardiothoracic transplant programs generally require that transplant recipients
      have family caregivers to assist them posttransplant. The burden of caregiving on
      the family members remains poorly understood. If caregivers' well-being is
      compromised by caregiving, it may bode poorly for transplant recipients' own
      health in the long-term posttransplant. We examined caregiver health-related
      quality of life (HRQOL) during the first year after their family member's
      transplant, its predictors and its relationship to subsequent patient survival.
      Adult (aged 18+) caregivers of 242 cardiothoracic transplant recipients (lung =
      134; heart = 108) completed assessments of demographics, psychosocial
      characteristics and caregiver burden at 2 months posttransplant, and HRQOL at 2,
      7 and 12 months posttransplant. Recipients' survival time was obtained from
      medical records. Caregiver HRQOL was generally high across the first-year
      posttransplant in emotional and social functioning; caregiver physical
      functioning significantly worsened. There were no differences by type of
      recipient transplant. Greater caregiver burden predicted poorer caregiver HRQOL
      in several physical domains at 12 months posttransplant. Transplant recipients
      whose caregivers had lower perceived general health at 12 months posttransplant
      showed poorer survival rates during the subsequent 7 years of follow up.
      Transplant teams should identify those caregivers at risk for poorer general
      health posttransplant to maximize positive outcomes for the entire family.

PMID- 22958760
TI  - Peer2ref: a peer-reviewer finding web tool that uses author disambiguation.
AB  - BACKGROUND: Reviewer and editor selection for peer review is getting harder for
      authors and publishers due to the specialization onto narrower areas of research
      carried by the progressive growth of the body of knowledge. Examination of the
      literature facilitates finding appropriate reviewers but is time consuming and
      complicated by author name ambiguities. RESULTS: We have developed a method
      called peer2ref to support authors and editors in selecting suitable reviewers
      for scientific manuscripts. Peer2ref works from a text input, usually the
      abstract of the manuscript, from which important concepts are extracted as
      keywords using a fuzzy binary relations approach. The keywords are searched on
      indexed profiles of words constructed from the bibliography attributed to authors
      in MEDLINE. The names of these scientists have been previously disambiguated by
      coauthors identified across the whole MEDLINE. The methods have been implemented
      in a web server that automatically suggests experts for peer-review among
      scientists that have authored manuscripts published during the last decade in
      more than 3,800 journals indexed in MEDLINE. CONCLUSION: peer2ref web server is
      publicly available at http://www.ogic.ca/projects/peer2ref/.

PMID- 22958759
TI  - Does asthma control as assessed by the asthma control test reflect airway
      inflammation?
AB  - BACKGROUND AND AIMS: The treatment of asthmatic patients is particularly focused
      on the control of symptoms as well as functional and inflammatory parameters. In
      our study, we investigated the relationship between the asthma control test (ACT)
      which evaluates symptoms and airway inflammation and functional parameters.
      MATERIALS AND METHODS: Stable asthmatic patients admitted to our pulmonary
      outpatient clinic were enrolled in the study consecutively and underwent the ACT,
      pulmonary function tests and methacholine bronchial provocation test (MBPT).
      Additionally, fractional exhaled nitric oxide level (FeNO) and induced sputum
      cell distribution were assessed. All these parameters were re-evaluated at the
      third month after adjusting medications of the patients according to baseline ACT
      scores. RESULTS: Of the 101 patients screened, we analyzed 83 who proceeded to
      the follow up visit. At the baseline visit, 8 were totally controlled, 36
      partially controlled and 39 uncontrolled according to ACT. At the follow up
      visit, 10 were totally controlled, 39 partially controlled and 34 uncontrolled.
      Comparison of the two visits in terms of all parameters revealed significant
      reductions only in the percentages of patients with MBPT positivity (p = 0.029)
      and FeNO levels > 20 ppb (p = 0.025) at follow up. The percentages of patients
      with FeNO > 20 ppb, MBPT positivity, induced sputum eosinophilia or induced
      sputum neutrophilia did not show significant differences between totally
      controlled, partially controlled and uncontrolled groups at both baseline and
      follow up visits. CONCLUSION: Although the ACT scores did not show significant
      correlations with the airway inflammation parameters tested in this study, a
      marked reduction in the percentage of patients with MBPT positivity and FeNO > 20
      ppb at follow up may suggest the importance of the control concept in the
      management of asthma.

PMID- 22958762
TI  - The pharyngo-tympano-stapedial variant of the middle meningeal artery. A case
      report.
AB  - Atypical origin of the middle meningeal artery from the cervical internal carotid
      artery is a rare angiographic finding. We describe a case of the pharyngo-tympano
      stapedial variant of the middle meningeal artery in a young patient. In this
      vascular variation the proximal segment of the middle meningeal artery,
      corresponding to an annexed inferior tympanic artery, originates from the
      cervical carotid artery. Then over the promontory it unites with the superior
      tympanic artery and continues with its intracranial course via the petrous
      branch.

PMID- 22958763
TI  - Anomalous origins of bilateral vertebral arteries in a child with Down syndrome
      and Moyamoya disease. A case report.
AB  - Variations in vertebral artery origin and course are well-described in the
      literature. The origin of right vertebral artery from the right common carotid
      artery is an extremely rare variant. We describe a unique case of a child with
      Down syndrome with variant origins of bilateral vertebral artery, an aberrant
      right subclavian artery and concomitant Moyamoya disease of intracranial
      circulation. The presence of variations of the origin and course of
      craniocervical arteries might have profound implications in angiographic and
      surgical procedures and hence it is of great importance to be aware of such a
      possibility.

PMID- 22958764
TI  - Cerebral blood flow and metabolism measurement using positron emission tomography
      before and during internal carotid artery test occlusions: feasibility of rapid
      quantitative measurement of CBF and OEF/CMRO(2).
AB  - Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with
      cerebral blood flow (CBF) study is a sensitive test for predicting the outcome of
      permanent ICA occlusion. However, false negative results sometimes occur using
      single photon emission tomography (SPECT). We have recently developed a rapid
      positron emission tomography (PET) protocol that measures not only the CBF but
      also the cerebral oxygen metabolism before and during BTO in succession. We
      measured acute changes in regional CBF and OEF/CMRO(2) before and during BTO in
      three cases with large or giant cerebral aneurysms using the rapid PET protocol.
      Although no patients showed ischemic symptoms during BTO, PET studies exhibited
      mildly to moderately decreased CBF (9~34%) compared to the values obtained before
      BTO in all cases. The average OEF during BTO was significantly increased (21% and
      43%) than that of before BTO in two cases. The two cases were considered to be
      non-tolerant for permanent ICA occlusion and treated without ICA sacrifice.
      Measurement of the CBF and OEF/CMRO(2) using a rapid PET protocol before and
      during BTO is feasible and can be used for accurate assessment of tolerance
      prediction in ICA occlusion.

PMID- 22958765
TI  - CE-MRA for follow-up of aneurysms post stent-assisted coiling.
AB  - This study compared the accuracy of contrast-enhanced MR angiography (CE-MRA) to
      intra-arterial cerebral angiography (IA-DSA) for assessment of intracranial
      aneurysms after stent-assisted coiling and to check if the presence of a stent in
      the parent artery diminishes the accuracy of CE-MRA. Consecutive patients with
      cerebral aneurysms treated by stent-assisted coiling were evaluated
      retrospectively. Matching follow-up CE-MRA and IA-DSA were evaluated separately.
      Evaluation included the presence of aneurysmal remnant, patency and stenosis of
      parent artery. Twenty-seven patients with 28 aneurysms and 33 matched CE-MRA and
      IA-DSA studies were evaluated. Nineteen aneurysmal remnants were seen on CE-MRA
      and 16 on IA-DSA. CE-MRA diagnosed three aneurysmal remnants not appreciated on
      IA-DSA. Five other remnants were larger on CE-MRA than IA-DSA. None of the
      remnants were missed on CE-MRA. Parent arteries were patent on both modalities.
      CE-MRA showed false stenosis of the stented artery in six cases and exaggerated
      stenosis in two. In 18 cases, CE-MRA showed a short focal "pseudo-stenosis" where
      the stent's marker bands were located. This was noted whenever the stent's marker
      bands were located in an artery with luminal diameter <=2 mm and was called
      "marker band effect". CE-MRA is an accurate technique for follow-up of aneurysms
      post stent-assisted coiling with excellent depiction of remnants in spite of the
      presence of a stent. Apparent stenosis of the stented parent artery on CE-MRA is
      often false or exaggerated. "Marker band effect" should be recognized as an
      artifact that appears when stent's marker bands are in a small artery.

PMID- 22958766
TI  - Initial experience of intracranial aneurysm embolization using the balloon
      remodeling technique with Scepter C, a new double-lumen balloon.
AB  - The balloon remodeling technique (BRT) was designed for endovascular treatment of
      wide-necked intracranial aneurysms. To date, the balloon catheters available have
      had a single lumen and suitable guidewires ranging from 0.010 to 0.012 inches. We
      describe the first case of aneurysm embolization using the BRT with the new
      double-lumen balloon catheter, Scepter C((r)), navigable on a 0.014-inch wire,
      and discuss the benefit of such a device.

PMID- 22958767
TI  - Wire-probing technique to revascularize subacute or chronic internal carotid
      artery occlusion.
AB  - During endovascular revascularization of subacute and chronic occlusion of the
      cervical internal carotid artery (ICA) it may be difficult to penetrate the
      lesion. Selecting the appropriate "true lumen", a remnant of what had been the
      arterial lumen, at the initial step may facilitate the procedure. Because plaque
      at the carotid bifurcation is known to propagate from the posterior wall, a
      gateway to this "true lumen" should exist in the anterior side of the occluded
      stump. This hypothesis was studied retrospectively in our series of
      revascularizing ICA subacute and chronic occlusion. Eleven patients underwent
      endovascular revascularization for symptomatic cervical ICA occlusion. Procedures
      were performed by initially penetrating the occluded stump with a guidewire,
      followed by supporting catheter advancement through the occluded segment to
      secure the distal normal arterial lumen. Cases were analyzed with regard to the
      location of initial guidewire penetration. Eight patients underwent successful
      revascularization. In five cases, the entry point to the occluded stump was
      located at the anterior side, and in three, at the posterior side. Two posterior
      stump penetration cases were met with resistance in guidewire advancement,
      whereas penetration was smooth in the anterior cases. In addition, two posterior
      stump penetration cases resulted in contrast stasis in the posterior ICA wall. In
      our series of revascularizing cervical ICA subacute and chronic occlusion,
      initially targeting the anterior side of the occluded stump resulted in favorable
      results. This may be the result of selecting the "true lumen" at the beginning of
      the procedure.

PMID- 22958768
TI  - Reversible cerebral vasoconstriction syndrome: treatment with multiple sessions
      of intra-arterial nimodipine and angioplasty.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute
      severe headache with or without additional neurological symptoms and reversible
      cerebral vasoconstriction. Unruptured aneurysms have been reported in some cases
      with RCVS. We describe a severe case of a 50-year-old woman with RCVS presenting
      as cortical subarachnoid hemorrhage. Cerebral angiogram demonstrated the typical
      angiographic findings of RCVS and two very small unruptured aneurysms of the left
      internal carotid artery. The patient was treated with calcium channel blockers
      and the two aneurysms were successfully treated endovascularly. On day 16 the
      patient developed new focal neurological symptoms (severe paraparesis) and was
      successfully treated with intraarterial nimodipine and angioplasty in multiple
      sessions.

PMID- 22958769
TI  - New insight into transient contrast enhancement on computed tomography after
      endovascular treatment of stroke.
AB  - Transient contrast enhancement on computed tomography following endovascular
      treatment of stroke is a recognized entity that has been previously reported.
      Technological advances in brain imaging now have the potential to explore and
      refine its proposed etiology. We describe three patients in whom the location of
      contrast enhancement correlates with decreased cerebral blood volume on pre
      therapeutic CT perfusion studies and with restricted diffusion on MRI. In this
      regard, contrast enhancement demarcated areas of completed cerebral infarction.
      The diagnostic and etiological implications are discussed.

PMID- 22958770
TI  - Fatal hemorrhage in cerebral proliferative angiopathy.
AB  - Cerebral proliferative angiopathy (CPA) is a rare vascular abnormality with
      several angiomorphological features that are distinct from brain arteriovenous
      malformations (AVMs). The natural history of CPAs indicates a lower risk for
      hemorrhage compared to brain AVMs. A 62-year-old woman presented with gait
      instability and dysarthria. MRI and angiography revealed a diffuse vascular
      network involving the tectum and cerebellar vermis with intermingled brain
      parenchyma. This lesion had no dominant feeder, high-flow arteriovenous shunt,
      flow-related aneurysm or highly dilated veins on angiogram. These findings were
      consistent with a diagnosis of CPA. During follow-up, she developed progressive
      gait instability and eye movement abnormalities, but no remarkable change was
      detected on the repeated MRI and angiography. Nine years later, she died of
      mesencephalic hemorrhage originating from the CPA. To the best of our knowledge,
      this is the first description of a patient with CPA who died as a result of the
      initial hemorrhage. It is important to recognize that a part of CPAs is
      aggressive and can be more vulnerable to critical hemorrhage.

PMID- 22958771
TI  - Use of the Penumbra system 054 plus low dose thrombolytic infusion for multifocal
      venous sinus thrombosis. A report of two cases.
AB  - Multifocal cerebral venous sinus thrombosis (CVST) has a high mortality rate
      especially when patients present with stupor or coma. Medical treatment including
      anticoagulation raises concerns about the associated high risk of intracerebral
      hemorrhage. Treatment of multifocal CVST with mechanical thrombectomy devices and
      local tPA infusion have previously been reported. However, these devices may have
      technical limitations. Success of the new-generation aspiration thrombectomy
      device like the Penumbra system has been reported in few cases of isolated CVST
      without the use of chemical thrombolysis. We describe two cases in which
      mechanical thrombectomy were used in conjunction with intra-sinus tPA infusion.
      Both cases were complicated and failed initial anticoagulation. Penumbra 054 was
      used in both cases. The Penumbra 054 is a novel device that has a bigger lumen
      which provides compatibility with other microcatheters, if additional therapies
      are required. The larger internal diameter of this catheter also allows for
      stronger thrombo-aspiration, potentially effecting more rapid sinus
      recanalization. Both cases showed remarkable clinical recovery without any major
      complications. This is the first reported simultaneous use of the Penumbra system
      054 along with tPA infusion. New devices such as the Penumbra system may offer
      additional therapeutic options in the treatment of multifocal CVST.

PMID- 22958772
TI  - Direct percutaneous carotid artery stenting for a patient with absence of the
      common carotid artery.
AB  - A 54-year-old man with symptomatic internal carotid artery stenosis with absence
      of the common carotid artery (CCA), who had been treated with surgery and
      postoperative radiotherapy for tonsillar carcinoma, underwent direct percutaneous
      carotid artery stenting (CAS). To our knowledge, this is the first report of
      direct percutaneous carotid artery stenting (CAS) for a patient with absent CCA.

PMID- 22958773
TI  - Intraprocedural angiographic CT as a valuable tool in the course of endovascular
      treatment of direct sinus cavernous fistulas.
AB  - This investigation aimed to demonstrate the potential of intraprocedural
      angiographic CT in monitoring complex endovascular coil embolization of direct
      carotid cavernous fistulas. Angiographic CT was performed as a dual rotational 5
      s run with intraarterial contrast medium injection in two patients during
      endovascular coil embolization of direct carotid cavernous fistulas.
      Intraprocedural angiographic CT was considered helpful if conventional 2D series
      were not conclusive concerning coil position or if a precise delineation of the
      parent artery was impossible due to a complex anatomy or overlying coil material.
      During postprocessing multiplanar reformatted and dual volume images of
      angiographic CT were reconstructed. Angiographic CT turned out to be superior in
      the intraprocedural visualization of accidental coil migration into the parent
      artery where conventional 2D-DSA series failed to reliably detect coil
      protrusion. The delineation of coil protrusion by angiographic CT allowed
      immediate correct coil repositioning to prevent parent artery compromising.
      Angiographic CT can function as a valuable intraprocedurally feasible tool during
      complex coil embolizations of direct carotid cavernous fistulas. It allows the
      precise visualization of the cerebral vasculature and any accidental coil
      protrusion can be determined accurately in cases where conventional 2D-DSA series
      are unclear or compromised. Thus angiographic CT might contribute substantially
      to reduce procedural complications and to increase safety in the management of
      endovascular treatment of direct carotid cavernous fistulas.

PMID- 22958774
TI  - Superior sagittal sinus dural arteriovenous fistulas treated by stent placement
      for an occluded sinus and transarterial embolization. A case report.
AB  - We describe a case of dural arteriovenous fistulas (DAVFs) involving the superior
      sagittal sinus (SSS) successfully treated with stent placement for an occluded
      sinus and transarterial embolization. A 61-year-old man who had been treated with
      anticoagulation for a known SSS thrombosis presented with a sudden onset of
      headache. CT scan revealed an intraventricular hemorrhage and cerebral
      angiography revealed DAVFs involving the SSS which had severe venous congestion
      and sinus occlusion. We treated this case with a staged endovascular approach
      which consisted of stent placement for the occluded sinus and transarterial
      intravenous embolization resulting in complete eradication of DAVFs.
      Recanalization of an occluded sinus by stent placement can reduce venous
      congestion and transarterial intravenous embolization can obliterate dural
      arteriovenous shunts. This staged strategy is feasible and should be considered a
      first option of treatment, especially for DAVFs which presented with intracranial
      hemorrhage and aggressive venous hypertension.

PMID- 22958775
TI  - Giant extracranial aneurysm of the internal carotid artery in neurofibromatosis
      type 1. A case report and review of the literature.
AB  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder characterized
      by cutaneous pigmentations, neurofibromas, Lisch nodules and neuroectodermal
      tumors. Supra-aortic vessel aneurysms may affect patients with NF-1 and can be
      associated with rupture, ischemic complications and compression symptoms. We
      describe a 48-year-old woman with NF-1 and an extracranial 3*5 cm right internal
      carotid artery aneurysm. After balloon test occlusion the patient was treated
      with parent artery sacrifice which led to significant shrinkage on follow-up MR
      and reduction of compression symptoms. The literature concerning internal carotid
      artery aneurysms associated with NF-1 is reviewed evaluating the possible
      therapeutic options.

PMID- 22958776
TI  - Traumatic pseudoaneurysms of the common carotid and vertebral artery in a four
      year-old child.
AB  - Pseudoaneurysms of the neck arteries are rare lesions usually traumatic and less
      frequently infectious in origin. They are often described as case reports. We
      describe here an unusual occurrence of pseudoaneurysms in the common carotid and
      vertebral artery in a four-year-old child victim of a stab wound in the neck
      treated by parent artery occlusion of the vertebral and common carotid arteries.

PMID- 22958777
TI  - Delayed transcutaneous extrusion of embolic coils after embolization of facial
      artery pseudoaneurysm.
AB  - External carotid artery (ECA) pseudoaneurysm is a known complication of treatment
      for head and neck cancer. We report a case of facial artery pseudoaneurysm
      arising after irradiation and salvage surgery for advanced tonsillar cancer, that
      was treated with endovascular embolization. The case was complicated by delayed
      transcutaneous extrusion of embolization coils through the skin of the anterior
      neck. We review the literature for related cases of coil extrusion in the head
      and neck, and discuss the implications for pseudoaneurysm surveillance.

PMID- 22958778
TI  - Cement embolization of a segmental artery after percutaneous vertebroplasty: a
      potentially catastrophic vascular complication.
AB  - Serious complications related to percutaneous vertebral augmentation procedures,
      vertebroplasty and kyphoplasty, are rare and most often result from local cement
      leakage or venous embolization. We describe an adult patient who underwent multi
      level, thoracic percutaneous vertebral augmentation procedures for painful
      osteoporotic compression fractures. The patient's percutaneous vertebroplasty
      performed at the T9 level was complicated by the asymptomatic, direct
      embolization of the right T9 segmental artery with penetration of cement into the
      radicular artery beneath the pedicle. We review the literature regarding the
      unusual occurrence of direct arterial cement embolization during vertebral
      augmentation procedures, discuss possible pathomechanisms, and alert clinicians
      to this potentially catastrophic vascular complication.

PMID- 22958779
TI  - Electrophysical therapy for managing diabetic foot ulcers: a systematic review.
AB  - To systematically assess published reports on the efficacy of electrophysical
      therapy in the treatment of diabetic foot ulcers, including electrical
      stimulation, low-level laser therapy, therapeutic ultrasound and electromagnetic
      therapy. Databases searched included MEDLINE, CINAHL, EMBASE and the Cochrane
      Central Register of Controlled Trials (CENTRAL) from 1966 to 2011. Studies
      reviewed included only randomised controlled trials (RCTs) on treatment with
      electrophysical modalities compared with sham, conventional treatment or other
      electrophysical modalities. Information extracted were objective measures of
      healing and data useful for the calculation of effect size. Eight RCTs were
      eventually included in the critical appraisal, with a combined total of 325
      participants. Five studies were conducted on electrical stimulation, two on
      phototherapy and one on ultrasound. All studies reported that the experimental
      group was significantly more favourable than the control or sham group. The
      pooled estimate of the number of healed ulcers of the three studies on electrical
      stimulation compared to the control or sham electrical stimulation showed
      statistical significance [mean difference of 2.8 (95% CI = 1.5-5.5, P = 0.002] in
      favour of electrical stimulation. The results indicated potential benefit of
      using electrophysical therapy for managing diabetic foot ulcers. However, due to
      the small number of trials ever conducted, the possibility of any harmful effects
      cannot be ruled out, and high-quality trials with larger sample sizes are
      warranted.

PMID- 22958780
TI  - Relationship between BODE index, quality of life and inflammatory cytokines in
      COPD patients.
AB  - BACKGROUND AND AIMS: Recently a multidimensional grading system based on the body
      mass index (B), degree of airflow obstruction (O), dyspnea (D) and exercise
      capacity (E) - the BODE index - has begun to be used increasingly for the
      evaluation of chronic obstructive pulmonary disease (COPD) patients. The aim of
      our study was to investigate the relationship between the BODE index and disease
      duration, annual exacerbation and hospitalization rates, health related quality
      of life and systemic inflammatory markers like C-reactive protein (CRP), tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-8. MATERIALS AND METHODS: In 88
      stable COPD patients we evaluated the body-mass index, pulmonary function tests,
      Modified Medical Research Council dyspnea scale and six-minute walk test (6 MWT).
      BODE scores were determined. Disease duration, number of exacerbations and
      hospitalization in the previous year were recorded. We also performed arterial
      blood gases analysis, administered the St. George's Respiratory Questionnaire
      (SGRQ) and measured serum levels of CRP, TNF-alpha, IL-8. RESULTS: According to
      BODE score 52% of patients were BODE 1, 21% BODE 2, 15% BODE 3 and 12% were BODE
      4. There was a significant relationship between BODE index and COPD stage as
      classified according to the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) (p < 0.001). Correlations between BODE score and disease duration
      (p = 0.011), number of exacerbations (p < 0.001) and hospitalizations (p < 0.001)
      in the last year were also observed. SGRQ symptom, activity, emotion scores and
      total scores were found to be significantly correlated to BODE (p < 0.001). Serum
      CRP levels and BODE were also correlated (p = 0.014); however, no correlation was
      found between serum levels of TNF-alpha and IL-8 and BODE. CONCLUSIONS: As the
      BODE index shows a strong correlation with various prognostic and follow up
      parameters of COPD and systemic inflammation, its use should be considered for
      the evaluation of COPD patients.

PMID- 22958781
TI  - Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in
      stage III non-small cell lung cancer patients.
AB  - PURPOSE: The aim of this retrospective cohort study was to assess treatment
      outcome, and acute pulmonary and esophageal toxicity using intensity modulated
      (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III
      non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Eighty-six patients
      with advanced stage NSCLC, treated with either IMRT only (66 Gy) or combined with
      (sequential or concurrent) chemotherapy were retrospectively included in this
      study. Overall survival and metastasis-free survival were assessed as well as
      acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity
      Scoring Criteria. RESULTS: Irrespective of the treatment modality, the overall
      survival rate for patients receiving 66 Gy was 71% (+/- 11%; 95% CI) after one
      year and 56% (+/- 14%) after two years resulting in a median overall survival of
      29.7 months. Metastasis-free survival was 73% (+/- 11%) after both one and two
      years. There were no statistically significant differences between the treatment
      groups. Treatment related esophageal toxicity was significantly more pronounced
      in the concurrent chemoradiotherapy group (p = 0.013) with no differences in
      pulmonary toxicity. CONCLUSIONS: This retrospective cohort study in advanced non
      small cell lung cancer patients shows that IMRT is an effective technique with
      acceptable acute toxicity, also when (sequentially or concomitantly) combined
      with chemotherapy.

PMID- 22958782
TI  - Feasibility, reliability, and clinical validity of the Test of Attentional
      Performance for Children (KiTAP) in Fragile X syndrome (FXS).
AB  - BACKGROUND: Attention and inhibition are core executive-function deficits in
      FRagile X syndrome (FXS). This pilot study evaluated the feasibility,
      reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial
      measure of attention and inhibition with an enchanted-castle theme, in an FXS
      cohort. METHODS: The 8-subtest KiTAP battery (as many subtests as each could
      perform) was given to 36 subjects with FXS, of variable age and
      cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to
      4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior
      Checklist-Community Edition (ABC-C) and Behavior Assessment System for Children,
      Second Edition (BASC-2). Feasibility, ceiling and basal effects, and data range
      and distribution analyses were used to eliminate outliers and invalid data
      points. Reproducibility of scores was analyzed using intraclass correlation
      coefficients (ICCs) and validity/clinical relevance was assessed by correlating
      KiTAP scores with ABC-C and BASC-2 scores. RESULTS: Most of the participants with
      FXS were able to complete the Alertness, Distractibility, Flexibility, and
      Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance
      subtests, and 20 to 25% completed the Sustained Attention and Divided Attention
      subtests. A panel of seven scores from four subtests were identified as feasible
      for most subjects, lacked excessive ceiling, basal, or learning effects,
      exhibited an acceptable range and distribution of scores, had good
      reproducibility (ICC > 0.7), and correlated with behavioral ratings for
      hyperactivity or attention (P < 0.01). Only minor differences in performance on
      the KiTAP were seen between mental age-matched cohorts of subjects with FXS and
      non-FXS intellectual disability. CONCLUSIONS: The KiTAP can be administered to
      cohorts with FXS over a wide range of function with valid reproducible scores.
      With additional validation, it could represent a useful outcome measure for
      assessment of attention/executive-function abilities in clinical trials targeted
      to these core deficits in FXS.

PMID- 22958783
TI  - Antimicrobial resistance programs in Canada 1995-2010: a critical evaluation.
AB  - BACKGROUND: In Canada, systematic efforts for controlling antibiotic resistance
      began in 1997 following a national Consensus Conference. The Canadian strategy
      produced 27 recommendations, one of which was the formation of the Canadian
      Committee on Antibiotic Resistance (CCAR). In addition several other
      organizations began working on a national or provincial basis over the ensuing
      years on one or more of the 3 identified core areas of the strategy. Critical
      evaluation of the major programs within Canada which focused on antimicrobial
      resistance and the identified core components has not been previously conducted.
      FINDINGS: Data was collected from multiple sources to determine the components of
      four major AMR programs that were considered national based on their scope or in
      the delivery of their mandates. Assessment of program components was adapted from
      the report from the International Forum on Antibiotic Resistance colloquium. Most
      of the programs used similar tools but only the Do Bugs Need Drugs Program (DBND)
      had components directed towards day cares and schools. Surveillance programs for
      antimicrobial resistant pathogens have limitations and/or significant sources of
      bias. Overall, there has been a 25.3% decrease in oral antimicrobial
      prescriptions in Canada since 1995, mainly due to decreases in beta lactams,
      sulphonamides and tetracyclines in temporal association with multiple programs
      with the most comprehensive and sustained national programs being CCAR and DBND.
      CONCLUSIONS: Although there has been a substantial decrease in oral antimicrobial
      prescriptions in Canada since 1995, there remains a lack of leadership and co
      ordination of antimicrobial resistance activities.

PMID- 22958785
TI  - Patient, doctor, disease, and informed consent.

PMID- 22958784
TI  - Arthroscopy or ultrasound in undergraduate anatomy education: a randomized cross
      over controlled trial.
AB  - BACKGROUND: The exponential growth of image-based diagnostic and minimally
      invasive interventions requires a detailed three-dimensional anatomical knowledge
      and increases the demand towards the undergraduate anatomical curriculum. This
      randomized controlled trial investigates whether musculoskeletal ultrasound
      (MSUS) or arthroscopic methods can increase the anatomical knowledge uptake.
      METHODS: Second-year medical students were randomly allocated to three groups. In
      addition to the compulsory dissection course, the ultrasound group (MSUS) was
      taught by eight, didactically and professionally trained, experienced student
      teachers and the arthroscopy group (ASK) was taught by eight experienced
      physicians. The control group (CON) acquired the anatomical knowledge only via
      the dissection course. Exposure (MSUS and ASK) took place in two separate lessons
      (75 minutes each, shoulder and knee joint) and introduced standard scan planes
      using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator
      combined with video tutorials. The theoretical anatomic learning outcomes were
      tested using a multiple-choice questionnaire (MCQ), and after cross-over an
      objective structured clinical examination (OSCE). Differences in student's
      perceptions were evaluated using Likert scale-based items. RESULTS: The ASK-group
      (n = 70, age 23.4 (20-36) yrs.) performed moderately better in the anatomical MC
      exam in comparison to the MSUS-group (n = 84, age 24.2 (20-53) yrs.) and the CON
      group (n = 88, 22.8 (20-33) yrs.; p = 0.019). After an additional arthroscopy
      teaching 1% of students failed the MC exam, in contrast to 10% in the MSUS- or
      CON-group, respectively. The benefit of the ASK module was limited to the
      shoulder area (p < 0.001). The final examination (OSCE) showed no significant
      differences between any of the groups with good overall performances. In the
      evaluation, the students certified the arthroscopic tutorial a greater advantage
      concerning anatomical skills with higher spatial imagination in comparison to the
      ultrasound tutorial (p = 0.002; p < 0.001). CONCLUSIONS: The additional
      implementation of arthroscopy tutorials to the dissection course during the
      undergraduate anatomy training is profitable and attractive to students with
      respect to complex joint anatomy. Simultaneous teaching of basic-skills in
      musculoskeletal ultrasound should be performed by medical experts, but seems to
      be inferior to the arthroscopic 2D-3D-transformation, and is regarded by students
      as more difficult to learn. Although arthroscopy and ultrasound teaching do not
      have a major effect on learning joint anatomy, they have the potency to raise the
      interest in surgery.

PMID- 22958787
TI  - Aberrations in the micro-RNA biogenesis machinery and the emerging roles of micro
      RNAs in the pathogenesis of cutaneous malignant melanoma.
AB  - Micro-RNAs (miRNAs) are small noncoding RNAs that play roles in the
      posttranscriptional regulation of gene expression. Since the seminal discovery
      that aberrant miRNA expression has a causative role in leukemogenesis, the
      involvement of miRNAs in cancer initiation, propagation, and metastasis has been
      widely studied. In this review, we provide a comprehensive summary of the
      literature on miRNAs in melanoma, specifically focusing on aberrations in
      cellular miRNA biogenesis and processing. These aberrations include genetic and
      epigenetic changes at the chromosomal level, alterations in the level of the
      miRNA-processing enzyme DICER, and the existence of competitive endogenous RNAs
      that serve as decoys for miRNAs and thus modulate their effective intracellular
      concentrations. We also discuss miRNA profiling in melanoma, review several
      miRNAs implicated in invasion, metastasis, proliferation, and apoptosis, and
      briefly summarize the cross talk between miRNAs and microphthalmia-associated
      transcription factor, the master transcriptional regulator of the melanocyte
      lineage. Finally, we summarize recent studies of miRNA expression as prognostic
      and predictive biomarkers, as well as initial experiments on the use of miRNAs
      and small interfering RNAs as therapeutic agents in melanoma.

PMID- 22958786
TI  - Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells
      of women undergoing IVF or ICSI and embryo transfer: clinical correlations.
AB  - BACKGROUND: The purpose of the study was to determine the incidence of survivin
      gene expression in human granulosa cells during ovarian stimulation in Greek
      women with normal FSH levels, undergoing IVF or ICSI and to discover any
      correlation between levels of gene expression and clinical parameters, efficacy
      of ovulation or outcomes of assisted reproduction. METHODS: Twenty nine women
      underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue
      recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus
      mature oocyte complexes were denuded and the granulosa cells were analyzed for
      each patient separately using quantitative reverse transcription polymerase chain
      reaction analysis for survivin gene expression with internal standard the ABL
      gene. RESULTS: The ABL and survivin mRNA were detected in granulosa cells in
      93.1%. The expression levels of survivin were significantly lower in normal women
      (male infertility factor) compared to women with tubal infertility factor (p =
      0.007). There was no additional statistically significant correlation between
      levels of survivin expression and estradiol levels or dosage of FSH for ovulation
      induction or number of dominant follicles aspirated or number of retrieved
      oocytes or embryo grade or clinical pregnancy rates respectively. CONCLUSIONS:
      High levels of survivin mRNA expression in luteinized granulosa cells in cases
      with tubal infertility seem to protect ovaries from follicular apoptosis. A
      subpopulation of patients with low levels of survivin mRNA in granulosa cells
      might benefit with ICSI treatment to bypass possible natural barriers of sperm
      oocyte interactions.

PMID- 22958788
TI  - Women, immigration, poverty and tuberculosis.

PMID- 22958790
TI  - Introduction: Pituitary disorders.

PMID- 22958789
TI  - Television viewing associated with adverse dietary outcomes in children ages 2-6.
AB  - The aim of this paper was to systematically review the evidence for the
      association between television viewing and diet in children ages 2-6. Data
      sources included PubMed, PsycINFO, EMBASE, ERIC, SportDISCUS, Sociological
      Abstracts, Web of Science and hand searches of reference lists of relevant
      articles. Twelve studies were reviewed in which the relationship between
      television viewing and diet was assessed in children between the ages of 2 and 6.
      All but one study reported significant relationship between television viewing
      time and adverse dietary outcomes. Parent-reported television viewing time was
      used to assay child television viewing in all included studies. Food frequency
      survey was the most frequent method of dietary assessment, and parent served as
      proxies for children in all studies. Lower fruit and/or vegetable intake was the
      most frequently reported dietary outcome, followed by increased energy intake
      with increased television viewing. The majority of studies reported adverse
      dietary outcomes with as little as 1 h of daily television exposure. While these
      results are consistent with recommendations from child health advocates to limit
      television viewing in young children, they also suggest that further efforts to
      limit television viewing in young children may be needed to aid in obesity
      prevention.

PMID- 22958791
TI  - Pituitary deficiencies.
AB  - Diabetes insipidus, arising from damage to or congenital abnormalities of the
      neurohypophysis, is the most common pituitary deficiency in animals.
      Hypopituitarism and isolated growth hormone or thyrotropin deficiency may result
      in growth abnormalities in puppies and kittens. In addition, treatment of
      associated hormone deficiencies, such as hypothyroidism and hypoadrenocorticism,
      in patients with panhypopituitarism is vital to restore adequate growth in
      dwarfed animals. Secondary hypoadrenocorticism is an uncommon clinical entity;
      however differentiation of primary versus secondary adrenal insufficiency is of
      utmost importance in determining optimal therapy. This article will focus on the
      pathogenesis, diagnosis and treatment of hormone deficiencies of the pituitary
      gland and neurohypophysis.

PMID- 22958792
TI  - Feline pituitary-dependent hyperadrenocorticism and insulin resistance due to a
      plurihormonal adenoma.
AB  - A 12-year-old female spayed domestic short-haired cat presented for lethargy,
      poor hair coat, alopecia, difficulty walking, and mild polyuria/polydipsia. The
      cat's skin tore easily in the neck area during routine restraint for blood draw.
      Physical examination, blood analysis, and ultrasound imaging were all consistent
      with pituitary-dependent hyperadrenocorticism (PDH) with secondary insulin
      resistant diabetes mellitus, which was nonketotic. Insulin therapy, fluids, and
      diet change were initiated for the diabetes mellitus and the owner reported
      improvement in clinical signs although the blood glucose measurements remained
      elevated. Surgical repair of the torn skin was successful. Although a guarded
      prognosis was given to the owner because of an advanced stage of
      hyperadrenocorticism, and the limited treatment options currently available for
      feline PDH, trilostane was agreed on as an initial therapeutic option. The day
      trilostane was to be initiated, the cat presented with dyspnea and the owner
      chose to euthanize. Because of the rarity of hyperadrenocorticism disease in the
      cat, permission was obtained by the owner for a necropsy to confirm suspected PDH
      as the underlying cause for insulin resistance and skin fragility syndrome.

PMID- 22958793
TI  - Recent advances in the diagnosis of Cushing's syndrome in dogs.
AB  - Hypercortisolism is a common condition in dogs and can be defined as the physical
      and biochemical changes that result from prolonged exposure to inappropriately
      high plasma concentrations of (free) cortisol, whatever its' cause. This disorder
      is often called Cushing's syndrome, after Harvey Cushing, the neurosurgeon who
      first described the human syndrome in 1932.

PMID- 22958794
TI  - Medical management of pituitary-dependent hyperadrenocorticism: mitotane versus
      trilostane.
AB  - Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs
      in the United States. Once a diagnosis is established, a decision must be made
      whether or not to pursue treatment, and if so, which medication to use.
      Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has
      been the most commonly used treatment for medical management. Its use is
      complicated and comes with many potential side effects, making many practitioners
      wary of its use. Recently, trilostane has been proven to be an effective
      treatment of pituitary-dependent hyperadrenocorticism and is approved for use in
      other countries. Treatment with trilostane is somewhat simpler and the incidence
      of side effects seems to be less when compared with mitotane therapy. Either
      treatment can be a safe and effective method of treatment for pituitary-dependent
      hyperadrenocorticism when the practitioner and client are well educated regarding
      their use and an appropriate monitoring protocol is used.

PMID- 22958795
TI  - Feline acromegaly.
AB  - Acromegaly, or hypersomatotropism, results from chronic, excessive secretion of
      growth hormone in the adult animal. The anabolic effects of growth hormone are
      exerted through the intermediary hormone, insulin-like growth factor 1, which is
      produced in the liver under the influence of growth hormone. Feline acromegaly is
      caused by a pituitary adenoma that secretes excessive amounts of growth hormone.
      Characteristic effects of excessive growth hormone secretion include the
      development of diabetes mellitus and growth of the acral segments of the body
      (jaw, extremities, skull, etc.). Acromegaly occurs in older, predominately male
      cats and is often associated with diabetes mellitus. Other clinical signs include
      stridor, enlargement of the jaw and extremities, lean weight gain, and
      organomegaly (heart, liver, kidney, etc.). Diagnosis is made by documentation of
      increased levels of growth hormone or insulin-like growth factor (or both) and
      demonstration of a pituitary mass via magnetic resonance imaging or computed
      tomography. The most effective treatment to date has been radiation therapy.
      Prognosis is fair to good with proper treatment.

PMID- 22958796
TI  - Mummified fetus in the thoracic cavity of a domestic short-haired cat.
AB  - This short communication describes the diagnosis, treatment, and clinical course
      of a domestic short-haired cat with diaphragmatic hernia in which the herniated
      structure in the thoracic cavity contained a mummified fetus. The cat was
      pregnant when rescued from the street and, days later, gave birth without
      abnormalities. Some months later, during an ovariohysterectomy, an abnormal
      localization of the uterus was observed, and at that time the case was referred
      to our center. A thoracic radiograph showed an abnormal thoracic mass cranial to
      the heart. The main suspicion was the presence of a thoracic hernia with the
      uterus herniated and containing a mummified fetus. A thoracotomy was performed to
      confirm the nature of the mass and reduce the diaphragmatic hernia. Although this
      clinical case is quite rare, a mummified fetus can be observed in thoracic
      hernias.

PMID- 22958797
TI  - Experiences of parents of substance-abusing young people attending support
      groups.
AB  - BACKGROUND: Substance abuse puts a burden on the physical and mental health and
      well-being of individuals and their families, particularly parents. Parents of
      substance-abusing young people are in need of professional or informal support
      and information. Potential and easy accessible sources are support groups. We
      explored the experiences of parents of substance-abusing young people attending
      support groups regarding several topics related to the substance-abuse of their
      son or daughter, the impact on their lives and their views on social support.
      METHODS: In this small-scale qualitative study based on in-depth interviews, we
      interviewed parents of substance-abusing young people focusing on their
      experiences concerning having a substance-abusing relative and attending the
      support group. RESULTS: All parents displayed feelings of stress and strain. They
      appeared to be highly satisfied with their participation in a support group. The
      expert status and knowledge of the facilitator and the provision of accurate
      information in the support group was also much appreciated. They were however
      dissatisfied by the attitude and knowledge of their GP. CONCLUSIONS: Our findings
      suggest that parents benefit from joining support groups, particularly in terms
      of emotional and social support and the practical information they received.

PMID- 22958798
TI  - Hepatitis B and C prevalence among the high risk groups of Pakistani population.
      A cross sectional study.
AB  - BACKGROUND: Hepatitis B and C cause significant morbidity and mortality
      worldwide. Little is known about the existence of hepatitis B and C among high
      risk groups of the Pakistani population. The present study was conducted to
      determine the prevalence of Hepatitis B and C in high risk groups, their
      comparison and the possible mode of acquisition by obtaining the history of
      exposure to known risk factors. METHODS: This cross sectional study was carried
      out in Karachi, from January 2007 to June 2008.HBsAg and Anti HCV screening was
      carried out in blood samples collected from four vulnerable or at risk groups
      which included injecting drug users (IDUs), prisoners, security personnel and
      health care workers (HCWs). Demographic information was recorded and the possible
      mode of acquisition was assessed by detailed interview. Logistic regression
      analysis was conducted using the STATA software. RESULTS: We screened 4202
      subjects, of these, 681 individuals were reactive either with hepatitis B or C.
      One hundred and thirty three (3.17%) were hepatitis B reactive and 548 (13.0%)
      were diagnosed with hepatitis C. After adjusting for age, security personnel,
      prisoners and IV drug users were 5, 3 and 6 times more likely to be hepatitis B
      reactive respectively as compared to the health care workers. IDUs were 46 times
      more likely to be hepatitis C positive compared with health care workers.
      CONCLUSION: The prevalence of hepatitis B and C was considerably higher in IDUs,
      prisoners and security personnel compared to HCWs group. Hepatitis C is more
      prevalent than hepatitis B in all these risk groups. Prevalence of hepatitis C
      increased with the increase in age. Use of unsterilized syringes, used syringes,
      body piercing and illicit sexual relations were found to be important associated
      risk factors for higher prevalence of Hepatitis B and C in these groups.

PMID- 22958800
TI  - Surgical significance of Fredet's area.

PMID- 22958799
TI  - Rationale of the BREAst cancer e-healTH [BREATH] multicentre randomised
      controlled trial: an internet-based self-management intervention to foster
      adjustment after curative breast cancer by decreasing distress and increasing
      empowerment.
AB  - BACKGROUND: After completion of curative breast cancer treatment, patients go
      through a transition from patient to survivor. During this re-entry phase,
      patients are faced with a broad range of re-entry topics, concerning physical and
      emotional recovery, returning to work and fear of recurrence. Standard and easy
      accessible care to facilitate this transition is lacking. In order to facilitate
      adjustment for all breast cancer patients after primary treatment, the BREATH
      intervention is aimed at 1) decreasing psychological distress, and 2) increasing
      empowerment, defined as patients' intra- and interpersonal strengths.
      METHODS/DESIGN: The non-guided Internet-based self-management intervention is
      based on cognitive behavioural therapy techniques and covers four phases of
      recovery after breast cancer (Looking back; Emotional processing; Strengthening;
      Looking ahead). Each phase of the fully automated intervention has a fixed
      structure that targets consecutively psychoeducation, problems in everyday life,
      social environment, and empowerment. Working ingredients include Information (25
      scripts), Assignment (48 tasks), Assessment (10 tests) and Video (39 clips
      extracted from recorded interviews). A non-blinded, multicentre randomised
      controlled, parallel-group, superiority trial will be conducted to evaluate the
      effectiveness of the BREATH intervention. In six hospitals in the Netherlands, a
      consecutive sample of 170 will be recruited of women who completed primary
      curative treatment for breast cancer within 4 months. Participants will be
      randomly allocated to receive either usual care or usual care plus access to the
      online BREATH intervention (1:1). Changes in self-report questionnaires from
      baseline to 4 (post-intervention), 6 and 10 months will be measured. DISCUSSION:
      The BREATH intervention provides a psychological self-management approach to the
      disease management of breast cancer survivors. Innovative is the use of patients'
      own strengths as an explicit intervention target, which is hypothesized to serve
      as a buffer to prevent psychological distress in long-term survivorship. In case
      of proven (cost) effectiveness, the BREATH intervention can serve as a low-cost
      and easy-accessible intervention to facilitate emotional, physical and social
      recovery of all breast cancer survivors. TRIAL REGISTRATION: This study is
      registered at the Netherlands Trial Register (NTR2935).

PMID- 22958801
TI  - Complications after Laparoscopic Roux-en-Y gastric bypass: a diagnostic
      challenge. Report of three cases and review of the literature.
AB  - The number of Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) procedures for morbid
      obesity and type 2 diabetes mellitus will increase worldwide, and therefore, an
      increase in perioperative morbidity can be anticipated. The authors present three
      cases based on different complications after LRYGB to demonstrate the diagnostic
      challenge that clinicians face in this particular group of patients. Also, a
      review of the literature covering the value of different imaging in these
      particular cases is provided by the authors. The role of imaging in the
      diagnostic process is discussed.

PMID- 22958802
TI  - Incisional hernia in day surgery: our personal experience.
AB  - Incisional hernia is one of the most common complications of laparotomy. Its
      repair with prosthesis has enabled a considerable improvement in the outcome,
      significantly reducing recurrences. This study analyses the results of open
      hernioplasty with mesh performed as a Day Surgery procedure in 42 patients
      between November 2008 and October 2010. The results were good, with low
      postoperative morbidity and recurrences (2.4%).

PMID- 22958803
TI  - Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although
      its spontaneous rupture is rare in Western countries, it constitutes a surgical
      emergency and is associated with high mortality. There is a lack of consensus as
      to the best approach and what parameters to use in choosing it. The three main
      approaches are conservative, endovascular and resection - the treatment of choice
      for acute abdominal bleeding. We report a case of hemoperitoneum following the
      spontaneous rupture of an unrecognized HCV-related HCC in a patient with no
      history of liver disease. The patient was successfully treated by emergency
      surgery, with resection of two segments of the left liver.

PMID- 22958804
TI  - Small bowel adenocarcinoma. Two case reports.
AB  - Introduction. Small bowel adenocarcinoma is a rare tumor, with a still not well
      studied tumorigenesis process, and non-specific symptoms that cause a delay in
      the diagnosis and consequently a worst outcome for the patient. Videocapsule
      endoscopy (VCE) and double-balloon enteroscopy (DBE) have revolutionized the
      diagnosis and management of patients with small bowel diseases. Surgery is the
      treatment of choice when feasible, while the chemotherapeutic approach is still
      not well standardized. Case reports. Two cases in 2 months (two women 52 and 72
      yr-old) of primary bowel adenocarcinoma is reported. The site of the tumor was in
      jejunum, instead of the most common site in duodenum. The patients underwent DBE
      with biopsy and ink mark. Laparoscopic-assisted bowel segmental resection was
      performed. The pathologic diagnosis was primary jejunum adenocarcinoma. No post
      operative mortality or significant morbidities were noted. Conclusion. The
      combination of DBE and laparocopic-assisted bowel surgery represents an ideal
      diagnostic and therapeutic method.

PMID- 22958805
TI  - Bilateral lung and liver hydatid cysts. Case report.
AB  - Introduction. Synchronous occurrence of pulmonary and hepatic hydatid cysts is an
      uncommon manifestation of hydatid disease that is observed in less than 10% of
      cases. We report a rare case of bilateral lung (with bronchial fistula) and liver
      cyst, surgically treated after medical therapy. Case report. A 44-year-old
      housewife reporting fever, anorexia and fatigue that had been present for the
      previous 20 days received diagnosis of bilateral lung and liver hydatid cyst.
      Because of the dimensions of right lung cyst and the successive bronchial
      fistolization, we proceeded to three-stage operation of two thoracotomies and a
      laparotomy to control the risk of further rupture. After surgery, all post
      operatives were uneventful. Complete resolution of the therapy with no evidence
      of recurrence at 2 years follow-up. Conclusion. We emphasize the need to search
      for additional hydatids in patients who present with either pulmonary or liver
      hydatids. The simultaneous treatment of liver and lung should be reserved to
      patients in good conditions; in all other cases, especially when one cyst is more
      symptomatic than the others or has more risk of rupture, we prefer to treat
      single cyst.

PMID- 22958806
TI  - Outlines on nanotechnologies applied to bladder tissue engineering.
AB  - Tissue engineering technologies are more and more expanding as consequence of
      recent developments in the field of biomaterial science and nanotechnology
      research. An important issue in designing scaffold materials is that of
      recreating the ECM (extra-cellular matrix) functional features - particularly ECM
      derived complex molecule signalling - to mimic its capability of directing cell
      growth and neotissue morphogenesis. In this way the nanotechnology may offer
      intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as
      nanomechanotransducer complex interacting with different cell nanosize proteins,
      especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold
      complex architectures, endowed with controlled geometry and functional
      properties, bottom-up approaches, based on molecular self-assembling of small
      building polymer units, are used, sometimes functionalizing them by incorporation
      of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a
      cell-integrin binding domain of fibronectin), whereas the top-down approaches are
      useful to fabricate micro/nanoscale structures, such as a microvasculature within
      an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced
      by electrospinning process, may be used to create fibrous scaffolds that can
      facilitate, given their nanostructured geometry and surface roughness, cell
      adhesion and growth. Also bladder tissue engineering may benefit by
      nanotechnology advances to achieve a better reliability of the bladder engineered
      tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured
      polymeric surfaces is significantly enhanced in comparison with that to
      conventional biomaterials. Moreover nanostructured surfaces of bladder engineered
      tissue show a decreased calcium stone production. In a bladder tumor animal
      model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue
      engineered replacement neobladder, appears to inhibit a carcinogenic relapse in
      bladder prosthetic material. Facing the future, a full success of bladder tissue
      engineering will mainly depend on the progress of both biomaterial
      nanotechnologies and stem cell biology research.

PMID- 22958807
TI  - Vacuum-assisted closure treatment of leg skin necrosis after angiographic
      embolization of a giant plexiform neurofibroma.
AB  - Type 1 neurofibromatosis is a relatively common inherited disease of the nervous
      system, with a frequency of almost 1 in 3000. It is associated with neurofibromas
      of various sites. Our case report is about the surgical management of a giant
      neurofibroma of the right gluteal fold in a 46-year-old male with NF1. The
      patient presented with increasing edema and accelerated growth of the mass; he
      underwent percutaneous embolization of lesion vessels that induced necrosis of
      the neurofibroma. The patient was taken to the operating room, where surgical
      resection of the bulk of the lesion was undertaken. The postoperative course was
      complicated by delayed wound closure managed with antibiotics and vacuum-assisted
      wound closure. Giant neurofibromas similar to this tumor require complex
      preoperative, intraoperative and postoperative management strategies. Surgical
      debulk is best managed with preoperative percutaneous embolization that help to
      avoid surgical bleeding. Postoperative delayed wound closure was managed with the
      application of negative pressure in a closed environment that triggers
      granulation and tissue formation.

PMID- 22958808
TI  - Anastomotic strictures in colorectal surgery: treatment with endoscopic balloon
      dilation.
AB  - The incidence of anastomotic stricture following colorectal surgery has increased
      in recent years. This complication is observed in 2-5% of all operated patients
      and is probably due to the greater number of low anastomoses performed with
      surgical staplers. We observed 31 patients with postoperative stricture, arising
      from one to nine months post-surgery. All patients had been treated for
      colorectal cancer and underwent endoscopy either during routine follow-up or for
      symptoms of stenosis. In 16 patients (group A) the stricture diameter was less
      than 4 mm and the patients had symptoms attributable to partial bowel
      obstruction. In the remaining 15 patients (group B), who had difficult bowel
      movements, the stricture diameter ranged from 4 to 8 mm. All patients were
      treated with endoscopic dilation using achalasia balloons. The results were
      considered good when the post-dilation anastomosis diameter achieved was at least
      13 mm, fair when it was 9-12 mm and poor when it was less than 9 mm. The short
      term results (3 weeks) were good in 27 patients (87.2%), fair in 3 patients
      (9.6%), and poor in 1 patient (3.2%). After several unsuccessful dilations, the
      latter was treated by surgery. Follow-up at 3-4 months of the remaining 30
      patients revealed good results in 20 (66.6%), fair in 6 (20%), and poor in 4
      (13.3%). In 1 of these 4 patients, cancer recurrence was observed and a new
      surgical resection was performed. In 2 patients a self-expandable metal stent was
      inserted for 4-6 weeks, with satisfactory results. In 1 patient a biodegradable
      polydioxanone stent was inserted with good results after 6 months. Follow-up at 3
      4 months showed good results in 25 patients. After 38 months, cancer recurrence
      in the area of the anastomosis was observed in 1 patient, who was treated
      surgically. Endoscopic dilatation should be considered the first therapeutic
      approach in case of anastomotic strictures, as it is immediately effective,
      repeatable, and does not preclude surgery if this should become necessary.

PMID- 22958809
TI  - Epidemiology and costs of hospital care for COPD in Puglia.
AB  - BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is currently
      the 5th cause of morbidity and mortality in the developed world and represents a
      substantial economic and social burden. The aim of this study is to report on
      hospital admissions and related costs of hospital treatment for COPD in the
      Puglia Region of Italy in the years 2005-2007. MATERIALS AND METHODS: Patients
      were selected who were hospitalized between 01/01/2005 and 31/12/2007 with ICD-9
      CM code: 490.xx: bronchitis not specified as acute or chronic; 491.xx: chronic
      bronchitis; 492.xx: emphysema; 493.xx: asthma; 494.xx: bronchiectasis; 496.xx:
      chronic airway obstruction not elsewhere classified; 518.81: acute respiratory
      failure as principal or secondary diagnosis. RESULTS: In the period 2005-2007,
      there were 73,721 hospital admissions for COPD registered in Puglia (25,690 in
      2005; 24,153 in 2006 and 23,878 in 2007) of which 34.3% were women, with no
      significant variation in the three years. There appears to be a negative trend in
      hospitalisations in Puglia for chronic bronchitis with ratios decreasing from
      359.4 per 100,000 population in 2005 to 307.9 per 100,000 in 2007. The overall
      cost of COPD for Apulian hospital trusts was ?272,293,182.85 over the 3-year
      period. CONCLUSIONS: Analysis of the data for hospital care, its costs and
      performance may be an important indicator of the efficacy of community care. In
      particular, the lack of reduction in admissions for COPD should lead decision
      makers to question both the appropriateness and quality of the care given.

PMID- 22958810
TI  - Barley grain for ruminants: A global treasure or tragedy.
AB  - Barley grain (Hordeum vulgare L.) is characterized by a thick fibrous coat, a
      high level of beta-glucans and simply-arranged starch granules. World production
      of barley is about 30 % of that of corn. In comparison with corn, barley has more
      protein, methionine, lysine, cysteine and tryptophan. For ruminants, barley is
      the third most readily degradable cereal behind oats and wheat. Due to its more
      rapid starch fermentation rate compared with corn, barley also provides a more
      synchronous release of energy and nitrogen, thereby improving microbial nutrient
      assimilation. As a result, feeding barley can reduce the need for feeding
      protected protein sources. However, this benefit is only realized if rumen
      acidity is maintained within an optimal range (e.g., > 5.8 to 6.0); below this
      range, microbial maintenance requirements and wastage increase. With a low pH,
      microbial endotoxines cause pro-inflammatory responses that can weaken immunity
      and shorten animal longevity. Thus, mismanagement in barley processing and
      feeding may make a tragedy from this treasure or pearl of cereal grains. Steam
      rolling of barley may improve feed efficiency and post-rumen starch digestion.
      However, it is doubtful if such processing can improve milk production and feed
      intake. Due to the need to process barley less extensively than other cereals (as
      long as the pericarp is broken), consistent and global standards for feeding and
      processing barley could be feasibly established. In high-starch diets, barley
      feeding reduces the need for capacious small intestinal starch assimilation,
      subsequently reducing hindgut starch use and fecal nutrient loss. With its
      nutritional exclusivities underlined, barley use will be a factual art that can
      either matchlessly profit or harm rumen microbes, cattle production, farm
      economics and the environment.

PMID- 22958811
TI  - Intensive long-term pulmonary rehabilitation program after oesophagectomy, a
      reflection.

PMID- 22958812
TI  - Absence of both MDR1 (ABCB1) and breast cancer resistance protein (ABCG2)
      transporters significantly alters rivaroxaban disposition and central nervous
      system entry.
AB  - Rivaroxaban is a novel factor 10a inhibitor, where hepatic metabolism and renal
      clearance account for its overall disposition. Renal impairment is known to
      increase rivaroxaban-associated bleeding risk in patients. As renal rivaroxaban
      clearance exceeds glomerular filtration rate, we suggested that active secretion
      by efflux transporters P-glycoprotein (MDR1) and breast cancer resistance protein
      (BCRP) contributes to rivaroxaban clearance. The ability of MDR1 and BCRP efflux
      transporters to mediate rivaroxaban transport in vitro was assessed in polarized
      cell monolayers. A significantly greater vectorial transport of rivaroxaban was
      observed in the basal to apical direction in Caco-2 cells, which was attenuated
      in the presence of the selective inhibitors. After oral administration of
      rivaroxaban (2 mg/kg), plasma concentrations did not significantly differ between
      wild-type and Mdr1a(def) or Bcrp(-/-) mice (n = 6 per group). However,
      rivaroxaban clearance was significantly reduced in Mdr1a/Mdr1b(-/-)/Bcrp(-/-)
      mice. Interestingly, rivaroxaban brain-to-plasma ratio did not differ in mice
      lacking only Mdr1a or Bcrp, but more than two times higher in the Mdr1a/Mdr1b(-/
      )/Bcrp(-/-) mice. Rivaroxaban is a shared substrate of MDR1 and BCRP. In vivo,
      MDR and BCRP function synergistically to modulate rivaroxaban disposition and
      appear to be particularly relevant to limiting its central nervous system entry.
      These data have important implications for safety and efficacy of anticoagulation
      therapy with rivaroxaban as many drugs in clinical use are known MDR1 inhibitors
      and loss-of-function polymorphisms in BCRP are common.

PMID- 22958813
TI  - A new journal and new global perspective on infection control and public health.

PMID- 22958814
TI  - Deterministic or stochastic choices in retinal neuron specification.
AB  - There are two views on vertebrate retinogenesis: a deterministic model dependent
      on fixed lineages and a stochastic model in which choices of division modes and
      cell fates cannot be predicted. In this issue of Neuron, He et al. (2012) address
      this question in zebrafish using live imaging and mathematical modeling.

PMID- 22958815
TI  - The clathrin adaptor complex responsible for somatodendritic protein sorting.
AB  - Neuronal proteins contain "address labels" that govern their localization. In
      this issue of Neuron, Farias et al. (2012) identify the machinery that recognizes
      one class of dendritic localization signals and establish its role in the
      polarization of dendritic proteins, including several postsynaptic receptors.

PMID- 22958816
TI  - Dendritic spikes veto inhibition.
AB  - How inhibition regulates dendritic excitability is critical to an understanding
      of the way neurons integrate the many thousands of synaptic inputs they receive.
      In this issue of Neuron, Muller et al. (2012) show that inhibition blocks the
      generation of weak dendritic spikes, leaving strong dendritic spikes intact.

PMID- 22958817
TI  - Neural mechanisms of stress resilience and vulnerability.
AB  - Exposure to stressful events can be differently perceived by individuals and can
      have persistent sequelae depending on the level of stress resilience or
      vulnerability of each person. The neural processes that underlie such clinically
      and socially important differences reside in the anatomical, functional, and
      molecular connectivity of the brain. Recent work has provided novel insight into
      some of the involved biological mechanisms that promises to help prevent and
      treat stress-related disorders. In this review, we focus on causal and
      mechanistic evidence implicating altered functions and connectivity of the
      neuroendocrine system, and of hippocampal, cortical, reward, and serotonergic
      circuits in the establishment and the maintenance of stress resilience and
      vulnerability. We also touch upon recent findings suggesting a role for
      epigenetic mechanisms and neurogenesis in these processes and briefly discuss
      promising avenues of future investigation.

PMID- 22958818
TI  - Synaptic energy use and supply.
AB  - Neuronal computation is energetically expensive. Consequently, the brain's
      limited energy supply imposes constraints on its information processing
      capability. Most brain energy is used on synaptic transmission, making it
      important to understand how energy is provided to and used by synapses. We
      describe how information transmission through presynaptic terminals and
      postsynaptic spines is related to their energy consumption, assess which
      mechanisms normally ensure an adequate supply of ATP to these structures,
      consider the influence of synaptic plasticity and changing brain state on
      synaptic energy use, and explain how disruption of the energy supply to synapses
      leads to neuropathology.

PMID- 22958819
TI  - Single action potentials and subthreshold electrical events imaged in neurons
      with a fluorescent protein voltage probe.
AB  - Monitoring neuronal electrical activity using fluorescent protein-based voltage
      sensors has been limited by small response magnitudes and slow kinetics of
      existing probes. Here we report the development of a fluorescent protein voltage
      sensor, named ArcLight, and derivative probes that exhibit large changes in
      fluorescence intensity in response to voltage changes. ArcLight consists of the
      voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and
      super ecliptic pHluorin that carries the point mutation A227D. The fluorescence
      intensity of ArcLight A242 decreases by 35% in response to a 100 mV
      depolarization when measured in HEK293 cells, which is more than five times
      larger than the signals from previously reported fluorescent protein voltage
      sensors. We show that the combination of signal size and response speed of these
      new probes allows the reliable detection of single action potentials and
      excitatory potentials in individual neurons and dendrites.

PMID- 22958820
TI  - How variable clones build an invariant retina.
AB  - A fundamental question in developmental neuroscience is how a collection of
      progenitor cells proliferates and differentiates to create a brain of the
      appropriate size and cellular composition. To address this issue, we devised
      lineage-tracing assays in developing zebrafish embryos to reconstruct entire
      retinal lineage progressions in vivo and thereby provide a complete quantitative
      map of the generation of a vertebrate CNS tissue from individual progenitors.
      These lineage data are consistent with a simple model in which the retina is
      derived from a set of equipotent retinal progenitor cells (RPCs) that are subject
      to stochastic factors controlling lineage progression. Clone formation in mutant
      embryos reveals that the transcription factor Ath5 acts as a molecular link
      between fate choice and mode of cell division, giving insight into the elusive
      molecular mechanisms of histogenesis, the conserved temporal order by which
      neurons of different types exit the cell cycle.

PMID- 22958821
TI  - Atoh1 governs the migration of postmitotic neurons that shape respiratory
      effectiveness at birth and chemoresponsiveness in adulthood.
AB  - Hindbrain neuronal networks serving respiratory, proprioceptive, and arousal
      functions share a developmental requirement for the bHLH transcription factor
      Atoh1. Loss of Atoh1 in mice results in respiratory failure and neonatal
      lethality; however, the neuronal identity and mechanism by which Atoh1-dependent
      cells sustain newborn breathing remains unknown. We uncovered that selective loss
      of Atoh1 from the postmitotic retrotrapezoid nucleus (RTN) neurons results in
      severely impaired inspiratory rhythm and pronounced neonatal death. Mice that
      escape neonatal death develop abnormal chemoresponsiveness as adults.
      Interestingly, the expression of Atoh1 in the RTN neurons is not required for
      their specification or maintenance, but is important for their proper
      localization and to establish essential connections with the preBotzinger Complex
      (preBotC). These results provide insights into the genetic regulation of neonatal
      breathing and shed light on the labile sites that might contribute to sudden
      death in newborn infants and altered chemoresponsiveness in adults.

PMID- 22958822
TI  - Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to
      the somatodendritic domain of hippocampal neurons.
AB  - Plasma membranes of the somatodendritic and axonal domains of neurons are known
      to have different protein compositions, but the molecular mechanisms that
      determine this polarized protein distribution remain poorly understood. Herein we
      show that somatodendritic sorting of various transmembrane receptors in rat
      hippocampal neurons is mediated by recognition of signals within the cytosolic
      domains of the proteins by the MU1A subunit of the adaptor protein-1 (AP-1)
      complex. This complex, in conjunction with clathrin, functions in the neuronal
      soma to exclude somatodendritic proteins from axonal transport carriers.
      Perturbation of this process affects dendritic spine morphology and decreases the
      number of synapses. These findings highlight the primary recognition event that
      underlies somatodendritic sorting and contribute to the evolving view of AP-1 as
      a global regulator of cell polarity.

PMID- 22958823
TI  - JNK3 perpetuates metabolic stress induced by Abeta peptides.
AB  - Although Abeta peptides are causative agents in Alzheimer's disease (AD), the
      underlying mechanisms are still elusive. We report that Abeta42 induces a
      translational block by activating AMPK, thereby inhibiting the mTOR pathway. This
      translational block leads to widespread ER stress, which activates JNK3. JNK3 in
      turn phosphorylates APP at T668, thereby facilitating its endocytosis and
      subsequent processing. In support, pharmacologically blocking translation results
      in a significant increase in Abeta42 in a JNK3-dependent manner. Thus, JNK3
      activation, which is increased in human AD cases and a familial AD (FAD) mouse
      model, is integral to perpetuating Abeta42 production. Concomitantly, deletion of
      JNK3 from FAD mice results in a dramatic reduction in Abeta42 levels and overall
      plaque loads and increased neuronal number and improved cognition. This reveals
      AD as a metabolic disease that is under tight control by JNK3.

PMID- 22958824
TI  - The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype
      ionotropic glutamate receptors.
AB  - The neurotransmitter glutamate mediates excitatory synaptic transmission by
      gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a
      subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and
      memory. We previously discovered two classes of AMPAR auxiliary proteins in C.
      elegans that modify receptor kinetics and thus change synaptic transmission.
      Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein
      that associates with both the related auxiliary subunit SOL-1 and with the GLR-1
      AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are
      disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and
      pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in
      trans can rescue sol-1 mutants, and this rescue depends on in cis expression of
      SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the
      adult nervous system to control AMPAR-mediated currents.

PMID- 22958825
TI  - Inhibitory control of linear and supralinear dendritic excitation in CA1
      pyramidal neurons.
AB  - The transformation of dendritic excitatory synaptic inputs to axonal action
      potential output is the fundamental computation performed by all principal
      neurons. We show that in the hippocampus this transformation is potently
      controlled by recurrent inhibitory microcircuits. However, excitatory input on
      highly excitable dendritic branches could resist inhibitory control by generating
      strong dendritic spikes and trigger precisely timed action potential output.
      Furthermore, we show that inhibition-sensitive branches can be transformed into
      inhibition-resistant, strongly spiking branches by intrinsic plasticity of branch
      excitability. In addition, we demonstrate that the inhibitory control of
      spatially defined dendritic excitation is strongly regulated by network activity
      patterns. Our findings suggest that dendritic spikes may serve to transform
      correlated branch input into reliable and temporally precise output even in the
      presence of inhibition.

PMID- 22958826
TI  - Separate, causal roles of the caudate in saccadic choice and execution in a
      perceptual decision task.
AB  - In contrast to the well-established roles of the striatum in movement generation
      and value-based decisions, its contributions to perceptual decisions lack direct
      experimental support. Here, we show that electrical microstimulation in the
      monkey caudate nucleus influences both choice and saccade response time on a
      visual motion discrimination task. Within a drift-diffusion framework, these
      effects consist of two components. The perceptual component biases choices toward
      ipsilateral targets, away from the neurons' predominantly contralateral response
      fields. The choice bias is consistent with a nonzero starting value of the
      diffusion process, which increases and decreases decision times for contralateral
      and ipsilateral choices, respectively. The nonperceptual component decreases and
      increases nondecision times toward contralateral and ipsilateral targets,
      respectively, consistent with the caudate's role in saccade generation. The
      results imply a causal role for the caudate in perceptual decisions used to
      select saccades that may be distinct from its role in executing those saccades.

PMID- 22958827
TI  - Attentional stimulus selection through selective synchronization between monkey
      visual areas.
AB  - A central motif in neuronal networks is convergence, linking several input
      neurons to one target neuron. In visual cortex, convergence renders target
      neurons responsive to complex stimuli. Yet, convergence typically sends multiple
      stimuli to a target, and the behaviorally relevant stimulus must be selected. We
      used two stimuli, activating separate electrocorticographic V1 sites, and both
      activating an electrocorticographic V4 site equally strongly. When one of those
      stimuli activated one V1 site, it gamma synchronized (60-80 Hz) to V4. When the
      two stimuli activated two V1 sites, primarily the relevant one gamma synchronized
      to V4. Frequency bands of gamma activities showed substantial overlap containing
      the band of interareal coherence. The relevant V1 site had its gamma peak
      frequency 2-3 Hz higher than the irrelevant V1 site and 4-6 Hz higher than V4.
      Gamma-mediated interareal influences were predominantly directed from V1 to V4.
      We propose that selective synchronization renders relevant input effective,
      thereby modulating effective connectivity.

PMID- 22958828
TI  - Rhythmic modulation of theta oscillations supports encoding of spatial and
      behavioral information in the rat hippocampus.
AB  - Oscillatory patterns of activity in various frequency ranges are ubiquitously
      expressed in cortical circuits. While recent studies in humans emphasized
      rhythmic modulations of neuronal oscillations ("second-order" rhythms), their
      potential involvement in information coding remains an open question. Here, we
      show that a rhythmic (~0.7 Hz) modulation of hippocampal theta power, unraveled
      by second-order spectral analysis, supports encoding of spatial and behavioral
      information. The phase preference of neuronal discharge within this slow rhythm
      significantly increases the amount of information carried by action potentials in
      various motor/cognitive behaviors by (1) distinguishing between the spikes fired
      within versus outside the place field of hippocampal place cells, (2)
      disambiguating place firing of neurons having multiple place fields, and (3)
      predicting between alternative future spatial trajectories. This finding
      demonstrates the relevance of second-order spectral components of brain rhythms
      for decoding neuronal information.

PMID- 22958830
TI  - Temporal integration of olfactory perceptual evidence in human orbitofrontal
      cortex.
AB  - Given a noisy sensory world, the nervous system integrates perceptual evidence
      over time to optimize decision-making. Neurophysiological accumulation of sensory
      information is well-documented in the animal visual system, but how such
      mechanisms are instantiated in the human brain remains poorly understood. Here we
      combined psychophysical techniques, drift-diffusion modeling, and functional
      magnetic resonance imaging (fMRI) to establish that odor evidence integration in
      the human olfactory system enhances discrimination on a two-alternative forced
      choice task. Model-based measures of fMRI brain activity highlighted a ramp-like
      increase in orbitofrontal cortex (OFC) that peaked at the time of decision,
      conforming to predictions derived from an integrator model. Combined behavioral
      and fMRI data further suggest that decision bounds are not fixed but collapse
      over time, facilitating choice behavior in the presence of low-quality evidence.
      These data highlight a key role for the orbitofrontal cortex in resolving sensory
      uncertainty and provide substantiation for accumulator models of human perceptual
      decision-making.

PMID- 22958829
TI  - Autism-associated promoter variant in MET impacts functional and structural brain
      networks.
AB  - As genes that confer increased risk for autism spectrum disorder (ASD) are
      identified, a crucial next step is to determine how these risk factors impact
      brain structure and function and contribute to disorder heterogeneity. With three
      converging lines of evidence, we show that a common, functional ASD risk variant
      in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key
      social brain circuitry in children and adolescents with and without ASD. MET risk
      genotype predicted atypical fMRI activation and deactivation patterns to social
      stimuli (i.e., emotional faces), as well as reduced functional and structural
      connectivity in temporo-parietal regions known to have high MET expression,
      particularly within the default mode network. Notably, these effects were more
      pronounced in individuals with ASD. These findings highlight how genetic
      stratification may reduce heterogeneity and help elucidate the biological basis
      of complex neuropsychiatric disorders such as ASD.

PMID- 22958831
TI  - Assessment of quality of life on home parenteral nutrition and after intestinal
      transplantation using treatment-specific questionnaires.
AB  - In order to investigate the quality of life on home parenteral nutrition and
      after intestinal transplantation using comparable questionnaires, the treatment
      specific quality of life questionnaire for adult patients on home parenteral
      nutrition was adapted for intestinal transplant recipients. Both instruments were
      composed of 8 functional scales, 9 symptom scales, 3 global health status/quality
      of life scales and 2 single items. A preliminary cross-sectional study enrolling
      all the patients currently cared at the same hospital was carried out. Exclusion
      criteria were age >= 60 years and hospitalization at time of assessment. Thirty
      three home parenteral nutrition patients (100% answered) and 22 intestinal
      transplant recipients (82% answered) were enrolled. Intestinal transplant
      recipients showed a better score in following scales: ability to holiday/travel
      (p < 0.001), fatigue (p = 0.022), gastrointestinal symptoms (p < 0.001), stoma
      management/bowel movements (p = 0.001) and global health status/quality of life
      (p = 0.012). A better score for ability to eat/drink (p = 0.070) and a worse
      score for sleep pattern (p = 0.100) after intestinal transplantation were also
      observed. The results of this preliminary study with specific instruments were
      consistent with the main expected improvement of the quality of life related to
      intestinal transplantation. Further studies in larger patient cohorts are
      required to confirm these data.

PMID- 22958832
TI  - The effects of high dose and highly fractionated radiation on distraction
      osteogenesis in the murine mandible.
AB  - The ability of irradiated tissue to support bony growth remains poorly defined,
      although there are anecdotal cases reported showing mixed results for the use of
      mandibular distraction osteogenesis after radiation for head and neck cancer.
      Many of these reports lack objective measures that would allow adequate analysis
      of outcomes or efficacy. The purpose of this experiment was to utilize a rat
      model of mandibular distraction osteogenesis after high dose and highly
      fractionated radiation therapy and to evaluate and quantify distracted bone
      formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions
      of external beam radiation (48 Gray) of the left mandible. Following a two week
      recovery period, an external frame distractor was applied and gradual distraction
      of the mandible was performed. Tissue was harvested after a twenty-eight day
      consolidation period. Gross, radiologic and histological evaluations were
      undertaken. Those animals subjected to pre-operative radiation showed severe
      attenuation of bone formation including bone atrophy, incomplete bridging of the
      distraction gap, and gross bony defects or non-union. Although physical
      lengthening was achieved, the irradiated bone consistently demonstrated marked
      damaging effects on the normal process of distraction osteogenesis. This murine
      model has provided reliable evidence of the injurious effects of high dose
      radiation on bone repair and regeneration in distraction osteogenesis utilizing
      accurate and reproducible metrics. These results can now be used to assist in the
      development of therapies directed at mitigating the adverse consequences of
      radiation on the regeneration of bone and to optimize distraction osteogenesis so
      it can be successfully applied to post-oncologic reconstruction.

PMID- 22958833
TI  - Ready for a world without antibiotics? The Pensieres Antibiotic Resistance Call
      to Action.
AB  - Resistance to antibiotics has increased dramatically over the past few years and
      has now reached a level that places future patients in real danger.
      Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are
      commensals and pathogens for humans and animals, have become increasingly
      resistant to third-generation cephalosporins. Moreover, in certain countries,
      they are also resistant to carbapenems and therefore susceptible only to
      tigecycline and colistin. Resistance is primarily attributed to the production of
      beta-lactamase genes located on mobile genetic elements, which facilitate their
      transfer between different species. In some rare cases, Gram-negative rods are
      resistant to virtually all known antibiotics. The causes are numerous, but the
      role of the overuse of antibiotics in both humans and animals is essential, as
      well as the transmission of these bacteria in both the hospital and the
      community, notably via the food chain, contaminated hands, and between animals
      and humans. In addition, there are very few new antibiotics in the pipeline,
      particularly for Gram-negative bacilli. The situation is slightly better for Gram
      positive cocci as some potent and novel antibiotics have been made available in
      recent years. A strong and coordinated international programme is urgently
      needed. To meet this challenge, 70 internationally recognized experts met for a
      two-day meeting in June 2011 in Annecy (France) and endorsed a global call to
      action ("The Pensieres Antibiotic Resistance Call to Action"). Bundles of
      measures that must be implemented simultaneously and worldwide are presented in
      this document. In particular, antibiotics, which represent a treasure for
      humanity, must be protected and considered as a special class of drugs.

PMID- 22958834
TI  - Robust reference intervals for liver function test (LFT) analytes in newborns and
      infants.
AB  - BACKGROUND: Reference intervals (RIs) are ranges of upper and lower limits of a
      given analyte which are used for a laboratory test to determine whether a disease
      is present or absent or to know if the patient is at risk for future disease
      states. In Ethiopia, a country with highly diversified population groups and
      geographical sites, there are no established RIs to metabolic analytes including
      the liver function test (LFT) analytes for the pediatric population though it has
      been known that liver function assessment in this population is vital as a result
      of varied vulnerability to both endogenous and xenobiotic substances. METHODS: A
      cross sectional study was conducted in Tikur Anbessa Specialized Hospital (TASH)
      and Teklehaymanot Health Center (THC) from November 2010 to April 2011. 117 cord
      blood (from newborns) and venous blood samples (from infants) were collected and
      analyzed using HumaStar 300. All pre-analytical, analytical and post-analytical
      aspects were thoroughly controlled. A robust, CLSI/ IFCC recommended, method was
      used for the determination of upper and lower end points covering 95% of the
      reference values of each analyte with respective 90% CIs using MedCalc(r)
      software. RESULTS: Combined RIs for newborns and infants were established for
      albumin, AST, ALP, direct bilirubin and total bilirubin to be 3.88-5.82 g/dl,
      16.1-55.4U/l, 130-831U/l, <0.41 mg/dl and <1.37 mg/dl respectively. But,
      separated RIs were indicated for ALT and GGT as 1.2-23.1U/l and 6.94-24.8U/l ALT;
      and 30.6-160.7U/L and 10-28.2U/l GGT for newborns and infants respectively. Some
      maternal and infantile factors were identified to affect the values of analytes.
      CONCLUSION: Almost all analytes were different from previously reported values
      for other target population of similar age group, kit insert values and adult
      values. So, interpretation of values of these analytes in newborns and infants of
      Ethiopian population sounds better to be performed by using such RIs taking the
      effect of some maternal and infantile factors in to account.

PMID- 22958835
TI  - Anti-inflammatory effects of montelukast on smoke-induced lung injury in rats.
AB  - AIM: To evaluate the effects of montelukast in smoke-induced lung injury.
      METHODS: 28 Wistar-Albino rats were enrolled into 4 groups with 7 rats per group.
      The healthy control group was exposed to fresh air while all rats in the 3
      experimental groups were exposed to cigarette smoke for 20 weeks for 2 hours per
      day. After histopathological verification of smoke induced lung injury,
      montelukast (0.1 mg/kg) dissolved in Na2CO3 was given in one group (MON), Na2CO3
      only was given in another group (MON control) and placebo was injected in the
      third group (COPD control) intraperitoneally for 21 days. At the end of this
      period blood samples were obtained for serum TNF-alpha assessment and light and
      electron microscopy analyses were performed on the lung tissues of sacrificed
      rats. RESULTS: Serum TNF-alpha levels in the MON group were significantly lower
      than in the MON control and COPD control groups (38.84 +/- 4.9 pg/ml, 77.5 +/-
      5.8 pg/ml and 79.2 +/- 6.9 pg/ml respectively, p < 0.05). Furthermore there was
      no statistically significant difference between the MON group and healthy
      controls with respect to serum TNF-alpha levels (38.84 +/- 4.9 pg/ml vs. 29.5 +/-
      3.6 pg/ml, p > 0.05). Light and electron microscopic evaluation of the lungs
      demonstrated that the total histopathological damage score of the lung samples
      was significantly lower in the MON group than in MON controls and COPD controls
      (5.14 +/- 0.5, 8.4 +/- 0.6 and 8.7 +/- 0.4 respectively, p < 0.05), while there
      was no significant difference between the MON group and healthy controls (5.1 +/-
      0.6 vs 2.3 +/- 0.2, p > 0.05). CONCLUSION: These findings suggest that
      montelukast might have a protective effect on smoke-induced lung injury in rats
      both from a histopathological and inflammatory point of view.

PMID- 22958836
TI  - ANCAC: amino acid, nucleotide, and codon analysis of COGs--a tool for sequence
      bias analysis in microbial orthologs.
AB  - BACKGROUND: The COG database is the most popular collection of orthologous
      proteins from many different completely sequenced microbial genomes. Per
      definition, a cluster of orthologous groups (COG) within this database
      exclusively contains proteins that most likely achieve the same cellular
      function. Recently, the COG database was extended by assigning to every protein
      both the corresponding amino acid and its encoding nucleotide sequence resulting
      in the NUCOCOG database. This extended version of the COG database is a valuable
      resource connecting sequence features with the functionality of the respective
      proteins. RESULTS: Here we present ANCAC, a web tool and MySQL database for the
      analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of
      freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by
      analyzing amino acid frequencies, codon usage, and GC-content in a species- or
      function-specific context. With respect to amino acids we, at least in part,
      confirm the cognate bias hypothesis by using ANCAC's NUCOCOG dataset as the
      largest one available for that purpose thus far. CONCLUSIONS: Using the NUCOCOG
      datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence
      information with the functional classification via COGs and provides a GUI for
      flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool
      for the analysis of sequence composition in the light of physiological roles and
      phylogenetic context without requirement of substantial programming-skills.

PMID- 22958838
TI  - A standardized method for the assessment of shoulder function.
AB  - The American Shoulder and Elbow Surgeons have adopted a standardized form for
      assessment of the shoulder. The form has a patient self-evaluation section and a
      physician assessment section. The patient self-evaluation section of the form
      contains visual analog scales for pain and instability and an activities of daily
      living questionnaire. The activities of daily living questionnaire is marked on a
      four-point ordinal scale that can be converted to a cumulative activities of
      daily living index. The patient can complete the self-evaluation portion of the
      questionnaire in the absence of a physician. The physician assessment section
      includes an area to collect demographic information and assesses range of motion,
      specific physical signs, strength, and stability. A shoulder score can be derived
      from the visual analogue scale score for pain (50%) and the cumulative activities
      of daily living score (50%). It is hoped that adoption of this instrument to
      measure shoulder function will facilitate communication between investigators,
      stimulate multicenter studies, and encourage validity testing of this and other
      available instruments to measure shoulder function and outcome.

PMID- 22958837
TI  - Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal
      epithelial cross talk and decidualization.
AB  - BACKGROUND: Beta-catenin is part of a protein complex associated with adherens
      junctions. When allowed to accumulate to sufficient levels in its
      dephosphorylated form, beta-catenin serves as a transcriptional co-activator
      associated with a number of signaling pathways, including steroid hormone
      signaling pathways. METHODS: To investigate the role of beta-catenin in
      progesterone (P4) signaling and female reproductive physiology, conditional
      ablation of Ctnnb1 from the endometrial mesenchymal (i.e. stromal and
      myometrial), but not epithelial, compartment was accomplished using the Amhr2-Cre
      mice. Experiments were conducted to assess the ability of mutant female mice to
      undergo pregnancy and pseudopregnancy by or through oil-induced decidualization.
      The ability of uteri from mutant female mice to respond to estrogen (E2) and P4
      was also determined. RESULTS: Conditional deletion of Ctnnb1 from the mesenchymal
      compartment of the uterus resulted in infertility stemming, in part, from
      complete failure of the uterus to decidualize. E2-stimulated epithelial cell
      mitosis and edematization were not altered in mutant uteri indicating that the
      mesenchyme is capable of responding to E2. However, exposure of ovariectomized
      mutant female mice to a combined E2 and P4 hormone regimen consistent with early
      pregnancy revealed that mesenchymal beta-catenin is essential for indirectly
      opposing E2-induced epithelial proliferation by P4 and in some mice resulted in
      development of endometrial metaplasia. Lastly, beta-catenin is also required for
      the induced expression of genes that are known to play a fundamental role in
      decidualization such as Ihh, Ptch1, Gli1 and Muc1 CONCLUSIONS: Three salient
      points derive from these studies. First, the findings demonstrate a mechanistic
      linkage between the P4 and beta-catenin signaling pathways. Second, they
      highlight an under appreciated role for the mesenchymal compartment in indirectly
      mediating P4 signaling to the epithelium, a process that intimately involves
      mesenchymal beta-catenin. Third, the technical feasibility of deleting genes in
      the mesenchymal compartment of the uterus in an effort to understand
      decidualization and post-natal interactions with the overlying epithelium has
      been demonstrated. It is concluded that beta-catenin plays an integral role in
      selective P4-directed epithelial-mesenchymal communication in both the estrous
      cycling and gravid uterus.

PMID- 22958839
TI  - Tears of the supraspinatus tendon associated with "hidden" lesions of the rotator
      interval.
AB  - Exploration of the rotator interval during repair of 116 apparently "isolated"
      supraspinatus tendon lesions have revealed "hidden lesions" of the coracohumeral
      ligament, the superior glenohumeral ligament, and the superior portion of the
      subscapularis tendon in 19 cases. Epidemiologic characteristics were comparable
      with other series with the exception of involvement of the dominant shoulder in
      95%. Arthroscopic computed tomography documented the lesion in 85% of the cases.
      At surgery the superficial layer of the coracohumeral ligament was always intact.
      After splitting of the rotator interval the lesion was visible and consisted of a
      local disinsertion of the common insertion of the superior glenohumeral ligament
      and the coracohumeral ligament and the deep superior fibers of the subscapularis
      tendon. It measured 1 to 2 cm in the superior-inferior direction. The biceps
      tendon was ruptured in 2 cases, subluxated in 14, and in its normal position in
      5. The treatment consisted of intraosseous reinsertion of the supraspinatus
      tendon, recentering of the biceps, and reinsertion of the torn structures to
      reconstruct a functional pulley system. The patients have been reviewed with a
      mean follow-up of 20 months (range 12 to 36 months). A secondary rupture of the
      long head of the biceps has been observed in 25% of the cases after recentering
      of the tendon.

PMID- 22958840
TI  - Influence of T-shift capsulorrhaphy on rotation and translation of the
      glenohumeral joint: An experimental study.
AB  - To evaluate changes in the response of capsuloligamentous restraints to
      translatory forces and rotation torques caused by experimental capsulorrhaphy (T
      shift modification of Bankart repair), eight cadaveric shoulders were tested.
      Measurements were taken in intact and vented specimens, after severance of the
      anterior capsule at the glenoid rim (creating an artificial Bankart lesion), T
      shaped incision of the anterior capsule, and refixation of the capsule (with a
      standard Bankart procedure) combined with tightening by T-shift. Rotation torques
      and translatory forces were applied in different positions of abduction with a
      specifically designed mounting apparatus that had four degrees of freedom.
      Dynamic and static measurements were performed with a tracking sysem that had six
      degrees of freedom. T-shift capsulorrhaphy restored the resistance of the
      capsuloligamentous restraints to translatory forces in all directions. This
      restoration was confirmed when we compared these results with data obtained from
      intact joints. No significant alteration of the centering mechanism resulting
      from rotation torques was observed, although the extent of external and internal
      rotation was remarkably decreased. This T-shift modification seems to produce a
      symmetric reduction of the volume of the capsule without significant displacement
      of the humeral head.

PMID- 22958841
TI  - Proprioception of the shoulder joint in healthy, unstable, and surgically
      repaired shoulders.
AB  - Shoulder proprioception was measured in 90 subjects who were assigned to three
      experimental groups: group 1 (n = 40), healthy college-age subjects; group 2 (n =
      30), patients with anterior instability; and group 3 (n = 20), patients who have
      had surgical reconstruction. Kinesthesia and joint position sense were measured
      with a specially designed proprioception testing device. The results revealed no
      significant differences in proprioception between dominant and nondominont
      shoulders in group 1 for any test condition. Significant differences (p < 0.05)
      were revealed between the unstable and uninvolved shoulder for both kinesthesia
      and joint position sense in group 2. No significant mean differences were
      revealed between the surgical and contralaterol shoulder in group 3 under any
      test condition. This series of studies provides evidence that proprioceptive
      deficits caused by partial deafferentiation result when copsuloligomentous
      structures are damaged. Reconstructive surgery appears to restore some of these
      proprioception characteristics.

PMID- 22958842
TI  - Use of Mitek anchoring for Bankart repair: A comparative, randomized, prospective
      study with traditional bone sutures.
AB  - The most common type of shoulder instability is posttraumatic anterior
      instability. Treatment is surgical. Of the several procedures used, the standard
      one is Bankart repair. However, this procedure is technically demanding. To
      simplify it a suture anchor such as Mitek anchors may be used. A prospective
      randomized study was conducted to compare Mitek anchors with bone sutures. The
      results showed that Mitek anchors shorten surgical time by making reattachment of
      the capsule easier. Shoulder muscle strength, range of motion, and frequency of
      recurrence were equally good in the anchor group and bone suture group. A
      roentgenographic method allowed exact measurement of placement of the anchors.
      This method showed at 2-year follow-up evaluation that the anchors were still in
      the anterior glenoid. No metal-related complications are found at the 2-year
      follow-up evaluation.

PMID- 22958843
TI  - Prevalence and etiology of symptomatic elbow osteoarthritis.
AB  - A total of 1150 consecutive patients attending fracture clinics were examined.
      One hundred fifty patients were excluded because they had fractures close to the
      elbow, multiple joint osteoarthritis, or posttraumatic osteoarthritis. This
      exclusion left a study population of 1000 patients. The prevalence of symptomatic
      elbow osteoarthritis was 2%. Osteoarthritis was found to be more common in men (p
      < 0.001) and in workers who did heavy manual labor (p < 0.016).

PMID- 22958844
TI  - Innervation of the extensor carpi radialis brevis and supinator muscles: Levels
      of origin and penetration of these muscular branches from the posterior
      interosseous nerve.
AB  - Dissections of 30 upper extremities from 15 skeletally mature cadavers were
      performed to identify the levels of origin and penetration of the innervation of
      the extensor carpi radialis brevis and supinator muscles. The humeroradial joint
      was used as a reference point for measurements. The most common pattern of
      extensor carpi radialis brevis innervation consisted of a single origin from the
      posterior interosseous nerve at the level of the humeroradial joint branching to
      penetrate the muscle at a level 30 mm to 60 mm distal to the humeroradial joint.
      The common innervation pattern of the supinator consisted of multiple origins
      from the posterior interosseous nerve at a level 0 mm to 30 mm distal to the
      humeroradial joint with multiple penetrations into the muscle at a level 10 mm to
      40 mm distal to the humeroradial joint. Although there is variability in the
      innervation of the extensor carpi radialis brevis and supinator, our data provide
      useful patterns concerning the anatomy of these muscular branches from the
      posterior interosseous nerve. More complete knowledge of this anatomy allows
      safer approaches for the surgical exposure of the radius and improved diagnosis
      and localization of radial nerve lesions in the proximal forearm, with improved
      predictability of recovery of nerve injuries.

PMID- 22958845
TI  - The supratrochleare dorsale accessory ossicle in the elbow.
AB  - Accessory ossicles about the elbow may occur more often than the literature would
      indicate. These bony ossicles frequently cause problems with misdiagnosis. The os
      supratrochleare dorsale, because it gets traumatized by elbow extension, may
      require removal to relieve pain, locking, and decreased range of motion.

PMID- 22958846
TI  - Stress fracture of the trochlea in an adolescent gymnast.

PMID- 22958847
TI  - Septic arthritis of the shoulder presenting as chronic anterior dislocation.

PMID- 22958848
TI  - Osteoarthritis caused by synovial chondromatosis of the shoulder.

PMID- 22958849
TI  - Shoulder arthroplasty after glenohumeral fusion.
AB  - We present a case of conversion of a glenohumeral fusion to an arthroplasty.
      Chronic pain in the scapulo-thoracic joint after shoulder arthrodesis, in the
      presence of a functional deltoid muscle, was judged to be the indication for
      conversion to a prosthesis. A deeply reamed glenoid fossa stabilized the
      prosthetic head. A glenoid component was not used. Pain relief was dramatic and
      permanent. Function was poor. Subjectively the patient was greatly improved. This
      solution is considered a salvage procedure for the rare instances of resistant,
      chronic pain originating in the scapulo-thoracic joint after glenohumeral fusion.

PMID- 22958850
TI  - Presidential address: Past, present, future Williamsburg, Virginia, November 1,
      1993.

PMID- 22958851
TI  - Influence of pH on the build-up of poly-L-lysine/heparin multilayers.
AB  - The effect of pH on the build-up of polyelectrolyte multilayers, PEMs, composed
      by poly-L-lysine and heparin onto two different substrates, silica and gold, has
      been studied by means of ellipsometry and quartz crystal microbalance with
      dissipation, QCM-D. Ellipsometry results indicate that the dry mass grows
      exponentially with the number of layers, and that this amount is larger as the pH
      values are raised. From QCM-D data the viscoelastic properties of the
      multilayered structure have been obtained. These data reflect that PEMs become
      more viscoelastic as the pH values are increased for silica substrates, while for
      gold the highest viscoelastic behavior is obtained at neutral pH and the elastic
      behavior becomes dominant as the pH is further increased or decreased. By
      combining these two surface techniques it has been also possible to determine the
      solvent content in the multilayers and reach a deeper understanding of the
      internal structure.

PMID- 22958852
TI  - Gelator-polysaccharide hybrid hydrogel for selective and controllable dye
      release.
AB  - In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular
      Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide
      (sodium alginate). A set of techniques including Fourier transform infrared (FT
      IR) spectroscopy, (1)H Nuclear Magnetic Resonance ((1)H NMR), X-ray powder
      diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had
      confirmed a beta-turn arrangement of PDB gelators and a semi-interpenetrating
      network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers
      and polysaccharide chains. The evaluation of physicochemical properties of
      hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better
      mechanical and water retention properties than LMWG hydrogels. The release study
      of dyes (model drug) from both LMWG and hybrid hydrogels was carried out.
      Compared with PDB based hydrogels, hybrid hydrogels show a selective and
      controllable release property for certain dyes. The results suggest LMWG
      polysaccharide hybrid gels may find potential applications as promising drug
      delivery vehicles for drug molecules.

PMID- 22958853
TI  - Ion size effects on the electrokinetics of salt-free concentrated suspensions in
      ac fields.
AB  - We analyze the influence of finite ion size effects in the response of a salt
      free concentrated suspension of spherical particles to an oscillating electric
      field. Salt-free suspensions are just composed of charged colloidal particles and
      the added counterions released by the particles to the solution that
      counterbalance their surface charge. In the frequency domain, we study the
      dynamic electrophoretic mobility of the particles and the dielectric response of
      the suspension. We find that the Maxwell-Wagner-O'Konski process associated with
      the counterions condensation layer is enhanced for moderate to high particle
      charges, yielding an increment of the mobility for such frequencies. We also find
      that the increment of the mobility grows with ion size and particle charge. All
      these facts show the importance of including ion size effects in any extension
      attempting to improve standard electrokinetic models.

PMID- 22958854
TI  - Influence of interfacial properties on Ostwald ripening in crosslinked
      multilayered oil-in-water emulsions.
AB  - The influence of interfacial crosslinking, layer thickness and layer density on
      the kinetics of Ostwald ripening in multilayered emulsions at different
      temperatures was investigated. Growth rates of droplets were measured by
      monitoring changes in the droplet size distributions of 0.5% (w/w) n-octane, n
      decane, and n-dodecane oil-in-water emulsions using static light scattering.
      Lifshitz-Slyozov-Wagner theory was used to calculate Ostwald ripening rates. A
      sequential two step process, based on electrostatic deposition of sugar beet
      pectin onto fish gelatin or whey protein isolate (WPI) interfacial membranes, was
      used to manipulate the interfacial properties of the oil droplets. Laccase was
      added to the fish gelatin-beet pectin emulsions to promote crosslinking of
      adsorbed pectin molecules via ferulic acid groups, whereas heat was induced to
      promote crosslinking of WPI and helix coil transitions of fish gelatin. Ripening
      rates of single-layered, double-layered and crosslinked emulsions increased as
      the chain length of the n-alkanes decreased. Emulsions containing crosslinked
      fish gelatin-beet pectin coated droplets had lower droplet growth rates (3.1+/
      0.3*10(-26) m(3)/s) than fish gelatin-stabilized droplets (7.3+/-0.2*10(-26)
      m(3)/s), which was attributed to the formation of a protective network. Results
      suggest that physical or enzymatic biopolymer-crosslinking of interfaces may
      reduce the molecular transport of alkanes between the droplets in the continuous
      phase.

PMID- 22958855
TI  - Effect of fulvic acid on neodymium uptake by goethite.
AB  - Experimental studies of the interaction of aqueous neodymium (Nd), Suwannee River
      fulvic acid (FA), and solid phase goethite were conducted. Results from blank
      systems (individual Nd and FA), binary systems (Nd-goethite, FA-goethite, and Nd
      FA), and ternary systems (Nd-FA-goethite) at 0.1 mol/kg and 25 degrees C are
      reported. In the binary Nd-goethite system a classic sorption edge is observed,
      whereby virtually all Nd is removed from solution above the goethite point of
      zero charge (PZC). Similarly, the binary FA-goethite system exhibits strong FA
      sorption; However in this system near complete removal of FA from solution is
      observed below the goethite PZC. In the binary Nd-FA system, both aqueous Nd and
      FA feature a sharp decrease in concentration at ca. pH 9. Various experiments in
      the ternary system were conducted. For all concentrations, FA enhanced Nd
      sorption below the goethite PZC, attributed to the formation of a Type B ternary
      surface complex (mineral-ligand-metal ion). Notably, the 100 ppm FA ternary
      system showed anomalously high dissolved Nd in solution above the PZC (i.e., Nd
      sorption suppression) and a concomitant increase in goethite dissolution (~9 ppm
      total Fe(3+) observed above circa pH 9.5). Our results suggest that Nd-FA
      complexation plays a key role in Nd uptake by goethite, and that this process is
      largely governed by pH: Whereas at pHs below the goethite PZC, Nd-FA complexation
      facilitates Nd sorption, above the PZC, and particularly at elevated FA
      concentrations, the formation of aqueous Nd-FA complexes suppresses Nd removal.
      Moreover, under these conditions, goethite dissolution may also play a role in
      mitigating Nd uptake by goethite.

PMID- 22958856
TI  - National Institute of Allergy and Infectious Disease (NIAID) Funding for Studies
      of Hospital-Associated Bacterial Pathogens: Are Funds Proportionate to Burden of
      Disease?
AB  - BACKGROUND: Hospital-associated infections (HAIs) are associated with a
      considerable burden of disease and direct costs greater than $17 billion. The
      pathogens that cause the majority of serious HAIs are Enterococcus faecium,
      Staphylococcus aureus, Clostridium difficile, Klebsiella pneumoniae,
      Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species,
      referred as ESCKAPE. We aimed to determine the amount of funding the National
      Institute of Health (NIH) National Institute of Allergy and Infectious Diseases
      (NIAID) allocates to research on antimicrobial resistant pathogens, particularly
      ESCKAPE pathogens. METHODS: The NIH Research Portfolio Online Reporting Tools
      (RePORT) database was used to identify NIAID antimicrobial resistance research
      grants funded in 2007-2009 using the terms "antibiotic resistance,"
      "antimicrobial resistance," and "hospital-associated infection." RESULTS: Funding
      for antimicrobial resistance grants has increased from 2007-2009. Antimicrobial
      resistance funding for bacterial pathogens has seen a smaller increase than non
      bacterial pathogens. The total funding for all ESKCAPE pathogens was $ 22,005,943
      in 2007, $ 30,810,153 in 2008 and $ 49,801,227 in 2009. S. aureus grants received
      $ 29,193,264 in FY2009, the highest funding amount of all the ESCKAPE pathogens.
      Based on 2009 funding data, approximately $1,565 of research money was spent per
      S. aureus related death and $750 of was spent per C. difficile related death.
      CONCLUSIONS: Although the funding for ESCKAPE pathogens has increased from 2007
      to 2009, funding levels for antimicrobial resistant bacteria-related grants is
      still lower than funding for antimicrobial resistant non-bacterial pathogens.
      Efforts may be needed to improve research funding for resistant-bacterial
      pathogens, particularly as their clinical burden increases.

PMID- 22958857
TI  - When to perform a bronchial challenge with mannitol?

PMID- 22958858
TI  - Neodymium-yttrium-aluminum-garnet laser lysis of retained cortex after
      phacoemulsification cataract surgery.
AB  - PURPOSE: To describe the use of the neodymium-yttrium-aluminum-garnet (Nd:YAG)
      laser to lyse residual cortex after phacoemulsification cataract surgery and
      report the complications and outcomes of treatment. DESIGN: Interventional,
      retrospective case series. METHODS: Consecutive patients who underwent Nd:YAG
      laser treatment for residual cortex at the Kellogg Eye Center, University of
      Michigan, Ann Arbor, Michigan were identified by review of laser logs from 2005
      to 2011. The medical records were reviewed, and the course and complications of
      treatment were recorded. The main outcome measures were improvement in subjective
      vision and corrected distance visual acuity. RESULTS: Eighteen eyes of 18
      patients, mean age 66 +/- 11 years, were included. Eight eyes (44%) had
      intraoperative posterior capsule rupture. Before treatment with the Nd:YAG laser,
      all patients had subjective visual complaints, with 6 patients reporting counting
      fingers or worse visual acuity. Eleven patients (61%) were successfully treated
      with 1 session of cortical lysis, while 5 patients underwent 2 and 2 patients
      underwent 3 or more treatments. Five patients (28%) had elevated intraocular
      pressure (IOP) within 1 day of treatment, and 1 patient developed cystoid macular
      edema. All patients had resolution of subjective visual symptoms, and at final
      follow-up corrected distance acuity was 20/25 or better in 13 patients (72%).
      CONCLUSIONS: The Nd:YAG laser can be used to lyse residual cortex after
      uncomplicated cataract surgery or cases with intraoperative posterior capsular
      rupture, and results in an improvement in subjective and corrected distance
      visual acuity. Elevated IOP is a common complication.

PMID- 22958859
TI  - Idiopathic full-thickness macular holes and the vitreomacular interface: a high
      resolution spectral-domain optical coherence tomography study.
AB  - PURPOSE: To analyze the vitreomacular interface in idiopathic full-thickness
      macular holes (MHs) using spectral-domain optical coherence tomography. DESIGN:
      Prospective cross-sectional case series. METHODS: Ninety-one eyes of 86
      consecutive patients with a MH were examined by spectral-domain optical coherence
      tomography. The vitreomacular interface was assessed and the presence or absence
      of an operculum was analyzed. RESULTS: Fifty-two eyes had a stage 2 MH, 12 eyes a
      stage 3 MH, and 27 eyes a stage 4 MH. No posterior hyaloid membrane was detected
      in any eyes with a stage 4 MH. In 35 (54.7%) of the 64 eyes with an MH without a
      complete posterior vitreous detachment (PVD), we saw a perifoveal PVD with
      vitreofoveal adhesion and partial dehiscence of the raised inner retina with an
      outer retinal separation in the MHs. In 24 (37.5%) of the 64 eyes without a
      complete PVD, an operculum, which is a hyperreflective structure of the foveal
      retina, was in front of the MH. The posterior hyaloid membrane was separated
      completely but adhered to the optic disc. In 2 (3.1%) of the 64 eyes without a
      complete PVD, the posterior hyaloid membrane was separated from the macula
      without an operculum. In 3 (4.7%) of the 64 eyes without a complete PVD,
      vitreofoveal adhesion on both edges of the hole was connected to the taut
      posterior hyaloid membrane without an operculum. CONCLUSIONS: The vitreomacular
      interface had 4 configurations in MHs without a complete PVD. Approximately 55%
      of cases with an open roof in the eyes without a complete PVD may be at risk for
      progression to operculum formation (loss of retinal tissue).

PMID- 22958860
TI  - Efficacy of hormonal suppression in a patient with chyluria due to
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting almost
      exclusively young women, characterised by abnormal proliferation of atypical
      smooth muscle cells. We describe a young woman presenting with chyluria secondary
      to the presence of a large retroperitoneal lymphangioleiomyoma.
      Immunohistochemical analysis revealed HMB45-negative LAM cells (HMB45 staining is
      absent only in rare cases) expressing low levels of estrogen receptors. Estrogen
      suppressive treatment with triptoreline, a synthetic analogue of Gn-RH, resulted
      in dramatic reduction of the retroperitoneal mass size. The role of estrogens in
      the pathogenesis of LAM remains poorly understood, and hormonal therapy is still
      debated, but this case suggests that at least in some LAM patients, possibly
      those with HMB45-negative disease and estrogen receptor expression, hormonal
      therapy may be effective in controlling the disease process.

PMID- 22958861
TI  - The need for tobacco cessation in a free clinic population.
AB  - INTRODUCTION: Free clinics are a unique safety net provider in that they
      exclusively serve the uninsured. Because free clinic providers are often
      volunteers, it is unclear whether uninsured patients seeking care in these
      clinics receive evidence-based tobacco cessation support. Here we report baseline
      data on prevalence and correlates of tobacco use and provider cessation advice
      among a sample of uninsured patients at six free clinics. METHODS: Patient exit
      interviews were conducted after a healthcare provider visit. Logistic regression
      analysis was used to assess correlates of tobacco use. RESULTS: Of the 158
      patients interviewed, 83 (53%) were tobacco users. Tobacco use was less likely
      among Hispanics (AOR 0.13 [95% CI 0.03-0.64]) and high school graduates (AOR=0.20
      [95% CI 0.08-0.55]). Among tobacco users, 62% made at least one quit attempt in
      the past year and the majority were in the Contemplation (33%) or Preparation
      (39%) stage of readiness. 70% of all patients were screened in the past 3 months,
      although screening was more likely among tobacco users than nonusers (AOR 3.56
      [95% CI 1.47-8.61]). At the current visit, 18% of tobacco users were advised to
      quit and 16% were asked if they were willing to quit. CONCLUSIONS: The prevalence
      of tobacco use among uninsured free clinic patients was more than twice the
      national average. There is substantial opportunity to increase tobacco screening
      among all patients and cessation advice among tobacco users. Free clinics present
      an untapped opportunity to reduce tobacco harm in a population at high risk for
      tobacco morbidity and mortality.

PMID- 22958862
TI  - Sensation-seeking predicts initiation of daily smoking behavior among American
      Indian high school students.
AB  - PURPOSE: American Indian (AI) youth have a high risk of smoking initiation.
      Sensation-seeking, defined as the tendency to seek novel and thrilling
      experiences, has been associated with smoking initiation in other groups but has
      never been examined in AI youth. METHODS: Data were from the Voices of Indian
      Teens Project (VOICES), a longitudinal study of AI youth from seven high schools
      in four AI communities in the western United States. Participants completed
      annual surveys in school over a three-year period. Our sample comprised 764
      students who were non-smokers at baseline. Smoking initiation was defined as
      endorsement of daily smoking after baseline. We used binary logistic regression
      to evaluate the association of baseline sensation-seeking with odds of daily
      smoking initiation, stratified by gender. RESULTS: Participants were 353 males
      and 411 females aged 13 to 21years at baseline. After adjusting for covariates,
      baseline sensation-seeking correlated with smoking initiation differently in
      males and females. Sensation-seeking did not predict daily smoking in males.
      Among females, however, higher sensation-seeking scores at baseline predicted
      daily smoking in both the unadjusted (odds ratio=1.4; 95% CI=1.1-1.8; p=0.005)
      and covariate-adjusted (odds ratio=1.3; 95% CI=1.0-1.6; p=0.04) models.
      CONCLUSION: Gender-specific prevention programs may be warranted in addressing
      different risk-factor profiles in this high-risk population.

PMID- 22958863
TI  - Do time perspective and sensation-seeking predict quitting activity among
      smokers? Findings from the International Tobacco Control (ITC) Four Country
      Survey.
AB  - Personality factors such as time perspective and sensation-seeking have been
      shown to predict smoking uptake. However, little is known about the influences of
      these variables on quitting behavior, and no prior studies have examined the
      association cross-nationally in a large probability sample. In the current study
      it was hypothesized that future time perspective would enhance - while sensation
      seeking would inhibit - quitting activity among smokers. It was anticipated that
      the effects would be similar across English speaking countries. Using a
      prospective cohort design, this cross-national study of adult smokers (N=8845)
      examined the associations among time perspective, sensation-seeking and quitting
      activity using the first three waves of data gathered from the International
      Tobacco Control Four Country Survey (ITC-4), a random digit dialed telephone
      survey of adult smokers from the United Kingdom, United States, Canada and
      Australia. Findings revealed that future time perspective (but not sensation
      seeking) was a significant predictor of quitting attempts over the 8-month follow
      up after adjusting for socio-demographic variables, factors known to inhibit
      quitting (e.g., perceived addiction, enjoyment of smoking, and perceived value of
      smoking), and factors known to enhance quitting (e.g., quit intention strength,
      perceived benefit of quitting, concerns about health effects of smoking). The
      latter, particularly intention, were significant mediators of the effect of time
      perspective on quitting activity. The effects of time perspective on quitting
      activity were similar across all four English speaking countries sampled. If
      these associations are causal in nature, it may be the case that interventions
      and health communications that enhance future-orientation may foster more quit
      attempts among current smokers.

PMID- 22958864
TI  - Family and peer predictors of substance use from early adolescence to early
      adulthood: an 11-year prospective analysis.
AB  - The focus of this study was social (i.e., family and peer) influences on
      substance use from early adolescence to early adulthood. A large, ethnically
      diverse sample of early adolescents (N=998) was followed from age 12 to age 23.
      We tested direct and indirect effects of parental monitoring, family relationship
      quality, and association with deviant peers on change in substance use across
      time. Outcomes for tobacco, alcohol, and marijuana use were analyzed as separate
      pathways within the same overall model. The results suggest that a significant
      shift in the nature of family influence occurred across adolescence and into
      early adulthood, but deviant peer influence was relatively consistent across this
      period. Specifically, parental monitoring and deviant peer association were
      predictive of substance use in early adolescence, but family relationship quality
      was a significant predictor across the transition to high school and generally
      continued to predict use into later adolescence, as did association with deviant
      peers. Deviant peers were the only significant predictor in early adulthood. Our
      results also suggested that parental monitoring and family relationship quality
      indirectly predicted later substance use by way of deviant peers, implying that
      an important aspect of the family context is its influence on choice of friends
      and peer group composition. Implications for family-based prevention and
      intervention are discussed.

PMID- 22958866
TI  - The role of social drinking motives in the relationship between social norms and
      alcohol consumption.
AB  - Social norms are key predictors of college student drinking. Additionally, the
      social reasons for consumption (i.e. social drinking motives) are important to
      understanding drinking behaviour. This study investigated the effects of social
      norms and social motives on alcohol consumption. A total of 229 college students
      completed an online questionnaire assessing their drinking behaviour, social
      drinking motives and their perceived drinking social norms. Drinking social norms
      were assessed as descriptive norms (i.e. the individual's perceived prevalence of
      alcohol consumption), and injunctive norms (i.e. the individual's perceived
      approval of drinking by their peers). Additionally, injunctive norms were further
      separated into distal (socially distant peers) and proximal (socially close
      peers). Hierarchical regression analyses revealed descriptive norms, proximal
      injunctive norms and social motives all independently predicted alcohol
      consumption. Additionally, the relationship between proximal injunctive norms and
      consumption, and descriptive norms and consumption was mediated by social
      motives. Lastly, there was a significant three-way interaction between
      descriptive norms, distal injunctive norms and social motives on drinking.
      Consideration of both the individual factors and the complex interplay between
      social norms and social motives on alcohol consumption is necessary to further
      understand drinking behaviour, and to develop more effective alcohol harm
      reduction strategies.

PMID- 22958865
TI  - Motivational Interviewing for adolescent substance use: a review of the
      literature.
AB  - Motivational Interviewing (MI) is a widely-used approach for addressing
      adolescent substance use. Recent meta-analytic findings show small but consistent
      effect sizes. However, differences in intervention format and intervention
      design, as well as possible mediators of change, have never been reviewed. This
      review of the literature summarizes the most up-to-date MI interventions with
      adolescents, looks at differences between intervention format and design, and
      discusses possible theory-based mechanisms of change. Of the 39 studies included
      in this review, 67% reported statistically significant improved substance use
      outcomes. Chi square results show no significant difference between interventions
      using feedback or not, or interventions combined with other treatment versus MI
      alone. The need for systematic investigation in theory-based mechanisms of change
      is presented.

PMID- 22958867
TI  - Parent-child communication and marijuana initiation: evidence using discrete-time
      survival analysis.
AB  - This study supplements existing literature on the relationship between parent
      child communication and adolescent drug use by exploring whether parental and/or
      adolescent recall of specific drug-related conversations differentially impact
      youth's likelihood of initiating marijuana use. Using discrete-time survival
      analysis, we estimated the hazard of marijuana initiation using a logit model to
      obtain an estimate of the relative risk of initiation. Our results suggest that
      parent-child communication about drug use is either not protective (no effect) or
      - in the case of youth reports of communication - potentially harmful (leading to
      increased likelihood of marijuana initiation).

PMID- 22958868
TI  - Mood and smoking behavior: the role of expectancy accessibility and gender.
AB  - Little is known about overall or gender-specific factors that may influence the
      relationship between negative affect and smoking behavior such as smoking
      expectancies. This paper presents a secondary analysis from a laboratory studying
      gender differences in smoking behavior following a musical mood induction
      [Weinberger, A.H., & McKee, S.A., 2012, Gender differences in smoking following
      an implicit mood induction. Nicotine & Tobacco Research, 14(5), 621-625]. The
      current analyses examine the role of expectancies (endorsement and accessibility)
      in the relationship of gender, affect, and smoking. Ninety adult smokers (50%
      female) were randomly assigned to a negative mood induction, positive mood
      induction, or neutral condition while completing a single laboratory session.
      Expectancy endorsement, expectancy accessibility, affect, and smoking topography
      were assessed following the mood induction. Female smokers with faster
      accessibility of negative reinforcement expectancies smoked more cigarettes, had
      longer puff durations, and had shorter inter-puff intervals. Women with faster
      expectancy accessibility were also more likely to endorse negative reinforcement
      smoking expectancies. This study was the first to demonstrate links among gender,
      mood, and accessibility of smoking-related beliefs. Information about the role of
      expectancy accessibility in smoking behavior can lead to both a better
      understanding of gender-specific mechanisms of smoking behavior and new
      directions for smoking treatment development.

PMID- 22958869
TI  - Tobacco withdrawal symptoms and urges to smoke in pregnant versus non-pregnant
      smokers.
AB  - We compared tobacco withdrawal in pregnant and non-pregnant smokers abstaining
      from smoking for 24h. Female smokers completed an internet-based questionnaire,
      including the Minnesota Nicotine Withdrawal Scale-Revised (MNWS). They also rated
      additional withdrawal items and strength of urge to smoke. Consenting women were
      randomized to either: (i) abstain from smoking for 24h or (ii) smoke as usual.
      After 24h they rated their withdrawal again. We included a 'smoking as usual'
      group as we wished to establish that smoking abstinence increased withdrawal
      symptoms. Two-hundred and seventy-five women completed both the initial and the
      24h questionnaire and reported abstaining (n=115, 17% pregnant) or smoking
      (n=160, 21% pregnant) as requested. Exclusively among abstinent smokers, we
      compared symptoms for the pregnant and non-pregnant groups. After 24h pregnant
      women had significantly lower scores than non-pregnant women for the mean MNWS
      (p=0.004) and for three individual MNWS symptoms (angry, p=0.010; anxious,
      p=0.048; impatient, p=0.011), with adjustments for baseline cigarette consumption
      and baseline withdrawal scores. Overall, on the first day of smoking abstinence,
      pregnant women are likely to report less severe tobacco withdrawal than non
      pregnant women.

PMID- 22958870
TI  - Factors affecting substance abuse treatment in Greece and their course during
      therapy.
AB  - The effective therapy of substance abuse is attributed to a wide range of
      factors. A relevant bibliography review has highlighted those factors, which are
      most commonly employed by mental health professionals: Readiness (recognition,
      taking steps, and ambivalence), Self-efficacy, Expectation about the therapy
      outcome, Satisfaction by the therapy treatment, Perceived Social Support,
      Depression/Anxiety/Stress levels of the client (clinical profile), Positive and
      Negative Emotions and the way in which clients realize the Meaning of Life. These
      factors have been thoroughly researched for the purposes of the current study
      during the different treatment stages of a residential treatment program. The
      sample included 157 clients. In total, four measurements of the factors have been
      conducted in the three basic stages of treatment (Counseling Centre, Residential
      Phase, and Social Re-integration). The analysis of the Repeated Measures Design
      revealed a statistically significant increase in factors, such as Taking Steps,
      Self-efficacy, Perceived Social Support, Positive Emotions and Meaning of Life,
      while it showed an important decrease in factors, such as Problem Recognition,
      Ambivalence, Depression and Stress. The findings of the study both confirm the
      important role already recognized factors play in treatment and present the
      impact new factors can have on the therapeutic outcome.

PMID- 22958873
TI  - Pain assessment and intensity in hospitalized children in Canada.
AB  - Numerous acute pediatric pain assessment measures exist; however, pain assessment
      is not consistently performed in hospitalized children. The objective of this
      study was to determine the nature and frequency of acute pain assessment in
      Canadian pediatric hospitals and factors influencing it. Pain assessment
      practices and pain intensity scores documented during a 24-hour period were
      collected from 3,822 children aged 0 to 18 years hospitalized on 32 inpatient
      units in 8 Canadian pediatric hospitals. Pain assessment was documented at least
      once within the 24 hours for 2,615/3,822 (68.4%) children; 1,097 (28.7%) with a
      pain measure alone, 1,006 (26.3%) using pain narratives alone, and 512 (13.4%)
      with both a measure and narrative. Twenty-eight percent of assessments were
      conducted with validated measures. The mean standardized pain intensity score was
      2.6/10 (SD 2.8); however, 33% of the children had either moderate (4-6/10) or
      severe (7-10/10) pain intensity recorded. Children who were older, ventilated, or
      hospitalized in surgical units were more likely to have a pain assessment score
      documented. Considerable variability in the nature and frequency of documented
      pain assessment in Canadian pediatric hospitals was found. These inconsistent
      practices and significant pain intensity in one-third of children warrant further
      research and practice change. PERSPECTIVE: This article presents current
      pediatric pain assessment practices and data on pain intensity in children in
      Canadian pediatric hospitals. These results highlight the variability in pain
      assessment practices and the prevalence of significant pain in hospitalized
      children, highlighting the need to effectively manage pain in this population.

PMID- 22958871
TI  - RON is not a prognostic marker for resectable pancreatic cancer.
AB  - BACKGROUND: The receptor tyrosine kinase RON exhibits increased expression during
      pancreatic cancer progression and promotes migration, invasion and gemcitabine
      resistance of pancreatic cancer cells in experimental models. However, the
      prognostic significance of RON expression in pancreatic cancer is unknown.
      METHODS: RON expression was characterized in several large cohorts, including a
      prospective study, totaling 492 pancreatic cancer patients and relationships with
      patient outcome and clinico-pathologic variables were assessed. RESULTS: RON
      expression was associated with outcome in a training set, but this was not
      recapitulated in the validation set, nor was there any association with
      therapeutic responsiveness in the validation set or the prospective study.
      CONCLUSIONS: Although RON is implicated in pancreatic cancer progression in
      experimental models, and may constitute a therapeutic target, RON expression is
      not associated with prognosis or therapeutic responsiveness in resected
      pancreatic cancer.

PMID- 22958872
TI  - Solid-organ transplantation in older adults: current status and future research.
AB  - An increasing number of patients older than 65 years are referred for and have
      access to organ transplantation, and an increasing number of older adults are
      donating organs. Although short-term outcomes are similar in older versus younger
      transplant recipients, older donor or recipient age is associated with inferior
      long-term outcomes. However, age is often a proxy for other factors that might
      predict poor outcomes more strongly and better identify patients at risk for
      adverse events. Approaches to transplantation in older adults vary across
      programs, but despite recent gains in access and the increased use of marginal
      organs, older patients remain less likely than other groups to receive a
      transplant, and those who do are highly selected. Moreover, few studies have
      addressed geriatric issues in transplant patient selection or management, or the
      implications on health span and disability when patients age to late life with a
      transplanted organ. This paper summarizes a recent trans-disciplinary workshop
      held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address
      issues related to kidney, liver, lung, or heart transplantation in older adults
      and to propose a research agenda in these areas.

PMID- 22958874
TI  - Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N
      methyl-D-aspartate receptors.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the
      pathophysiological mechanisms of the pain and hypersensitivity are incompletely
      understood. IBS patients frequently complain of pain in body regions
      somatotopically distinct from the gut, suggesting involvement of central
      hyperalgesic mechanisms. We tested the role of tonic peripheral impulse input by
      using both repetitive thermal stimuli to the leg and repetitive stimuli to the
      rectum. Changes in thermal/visceral pain sensitivity after nociceptive
      thermal/visceral repetitive stimulation were determined. A subset of IBS patients
      showed enhanced rectal/thermal pain sensitivity after repetitive thermal/rectal
      stimulation, respectively. IBS patients then received 60 mg dextromethorphan and
      placebo (diphenhydramine) in a randomized, double-blind, crossover trial. The
      results showed that 1) a subset of IBS patients had increased visceral/cutaneous
      hypersensitivity following a series of repetitive nociceptive stimuli and that 2)
      this increased pain sensitivity was blocked by administration of
      dextromethorphan. This is the first human study indicating that repetitive
      stimulation enhances a bidirectional mechanism of secondary hyperalgesia due to
      viscerosomatic facilitation in IBS patients. These unique findings elucidate
      mechanisms of somatic hypersensitivity in IBS patients and support an etiologic
      basis for abnormal N-methyl-D-aspartate receptor mechanisms that may be the
      target of future therapies for IBS. PERSPECTIVE: Repetitive stimulation enhances
      a bidirectional mechanism of secondary hyperalgesia due to viscerosomatic
      convergence in IBS patients. The findings elucidate unique mechanisms of
      somatic/visceral hypersensitivity in a subset of IBS patients and further support
      an etiologic basis for abnormal N-methyl-D-aspartate receptor mechanisms that may
      be future targets of therapies for IBS.

PMID- 22958875
TI  - Reliability and reproducibility of novel methodology for assessment of pressure
      pain sensitivity in pelvis.
AB  - Vestibulodynia, the most common type of chronic vulvovaginal pain, impairs the
      psychological, physical health of nearly 10% of women at some point in their
      lifetime. The aim of this investigation was to establish reliable standardized
      methodologies for assessment of pain sensitivity in vulvar mucosa and pelvic
      musculature. We enrolled 34 women with vestibulodynia and 21 pain-free controls.
      The participants underwent a nuanced exam that consisted of palpation of
      precisely located vulvar mucosal and pelvic muscle sites. These measurements
      remained highly stable when participants were reexamined after 2 weeks, with high
      within-examiner correlation. Vestibulodynia patients reported greater sensitivity
      than pain-free controls at the majority of examination sites, particularly at
      mucosal sites on the lower vestibule. The pain threshold measures at the lower
      mucosal sites were also associated with the participants' self-reported pain
      levels during intercourse. These mucosal pain threshold measurements were used to
      discriminate between vestibulodynia cases and controls with high sensitivity and
      specificity. This data supports the feasibility of contemporaneous assessment of
      vulvar mucosa and underlying musculature in the pelvic region, offering the hope
      of a more precise case definition for vestibulodynia and related disorders.
      PERSPECTIVE: This study describes performance characteristics of novel
      methodologies for assessing pelvic muscle and mucosal sensitivity. These pain
      sensitivity measures were reproducible and associated with subjective pain
      reports and vestibulodynia case status and represent an important step toward a
      more precise case definition for vestibulodynia and related disorders.

PMID- 22958876
TI  - Reasons for inadequate asthma control in children: an important contribution from
      the "French 6 Cities Study".

PMID- 22958878
TI  - HLA-A, -B, -DR allele group frequencies in 7007 kidney transplant list patients
      in 27 UK centres.
AB  - This observational study aims to determine the HLA specificity frequencies of
      patients on the UK renal transplant list, which can be used as a resource for
      those laboratories that support the UK renal transplant programme. Whilst the HLA
      specificity frequencies may differ from that of the general population, it is the
      individuals on the transplant list who are in need of a new kidney, which has to
      be provided from the general population. Any differences in protein allele
      frequencies between this patient population and the general population are likely
      to be minimal because of the very large number of patients included. The HLA-A, 
      B and -DR allele group frequencies from 7007 patients on the UK kidney transplant
      list (August, 2009) were analysed. HLA types had been submitted to NHSBT to
      register patients on the UK deceased donor kidney waiting list. The data were
      submitted from 27 different registering centres throughout the UK. Within this
      data set, 25 different HLA-A, 50 HLA-B and 18 HLA-DR allele groups were present.
      The most common allele groups at each locus were -A2 (phenotype frequency 42.6%),
      -B44 (phenotype frequency 23.3%) and -DR4 (phenotype frequency 29.8%). The least
      common allele groups at each locus were -A19, - A43, -B16, -B21, -B22, -B83 and 
      DR5. Reports of HLA frequency (protein allotype) data from populations as large
      as this are not readily available adding value to this observational study.

PMID- 22958877
TI  - Uterine biology in pigs and sheep.
AB  - There is a dialogue between the developing conceptus (embryo-fetus and
      associated placental membranes) and maternal uterus which must be established
      during the peri-implantation period for pregnancy recognition signaling,
      implantation, regulation of gene expression by uterine epithelial and stromal
      cells, placentation and exchange of nutrients and gases. The uterus provide a
      microenvironment in which molecules secreted by uterine epithelia or transported
      into the uterine lumen represent histotroph required for growth and development
      of the conceptus and receptivity of the uterus to implantation. Pregnancy
      recognition signaling mechanisms sustain the functional lifespan of the corpora
      lutea (CL) which produce progesterone, the hormone of pregnancy essential for
      uterine functions that support implantation and placentation required for a
      successful outcome of pregnancy. It is within the peri-implantation period that
      most embryonic deaths occur due to deficiencies attributed to uterine functions
      or failure of the conceptus to develop appropriately, signal pregnancy
      recognition and/or undergo implantation and placentation. With proper
      placentation, the fetal fluids and fetal membranes each have unique functions to
      ensure hematotrophic and histotrophic nutrition in support of growth and
      development of the fetus. The endocrine status of the pregnant female and her
      nutritional status are critical for successful establishment and maintenance of
      pregnancy. This review addresses the complexity of key mechanisms that are
      characteristic of successful reproduction in sheep and pigs and gaps in knowledge
      that must be the subject of research in order to enhance fertility and
      reproductive health of livestock species.

PMID- 22958879
TI  - Efficient procedures for the numerical simulation of mid-size RNA kinetics.
AB  - MOTIVATION: Methods for simulating the kinetic folding of RNAs by numerically
      solving the chemical master equation have been developed since the late 90's,
      notably the programs Kinfold and Treekin with Barriers that are available in the
      Vienna RNA package. Our goal is to formulate extensions to the algorithms used,
      starting from the Gillespie algorithm, that will allow numerical simulations of
      mid-size (~ 60-150 nt) RNA kinetics in some practical cases where numerous
      distributions of folding times are desired. These extensions can contribute to
      analyses and predictions of RNA folding in biologically significant problems.
      RESULTS: By describing in a particular way the reduction of numerical simulations
      of RNA folding kinetics into the Gillespie stochastic simulation algorithm for
      chemical reactions, it is possible to formulate extensions to the basic algorithm
      that will exploit memoization and parallelism for efficient computations. These
      can be used to advance forward from the small examples demonstrated to larger
      examples of biological interest. SOFTWARE: The implementation that is described
      and used for the Gillespie algorithm is freely available by contacting the
      authors, noting that the efficient procedures suggested may also be applicable
      along with Vienna's Kinfold.

PMID- 22958880
TI  - High load of multi-drug resistant nosocomial neonatal pathogens carried by
      cockroaches in a neonatal intensive care unit at Tikur Anbessa specialized
      hospital, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Cockroaches have been described as potential vectors for various
      pathogens for decades; although studies from neonatal intensive care units are
      scarce. This study assessed the vector potential of cockroaches (identified as
      Blatella germanica) in a neonatal intensive care unit setup in Tikur Anbessa
      Hospital, Addis Ababa, Ethiopia. METHODS: A total of 400 Blatella germanica
      roaches were aseptically collected for five consecutive months. Standard
      laboratory procedures were used to process the samples. RESULTS: From the
      external and gut homogenates, Klebsiella oxytoca, Klebsiella pneumoniae,
      Citrobacter spp. Enterobacter cloacae, Citrobacter diversus, Pseudomonas
      aeruginosa, Providencia rettgeri, Klebsiella ozaenae, Enterobacter aeruginosa,
      Salmonella C1, Non Group A streptococcus, Staphylococcus aureus, Escherichia
      coli, Acinetobacter spp. and Shigella flexneri were isolated. Multi-drug
      resistance was seen in all organisms. Resistance to up to all the 12
      antimicrobials tested was observed in different pathogens. CONCLUSION:
      Cockroaches could play a vector role for nosocomial infections in a neonatal
      intensive care unit and environmental control measures of these vectors is
      required to reduce the risk of infection. A high level of drug resistance pattern
      of the isolated pathogens was demonstrated.

PMID- 22958882
TI  - Treatment of mitral regurgitation: from sternotomy to percutaneous approach--a
      paradigm shift?

PMID- 22958883
TI  - Outcomes and safety of transcatheter pulmonary valve replacement in patients with
      large patched right ventricular outflow tracts.
AB  - BACKGROUND: Although globally accepted, the indication for implantation of the
      Melody((r)) (Medtronic Inc., Minneapolis, MN, USA) transcatheter pulmonary valve
      is limited to the treatment of haemodynamically dysfunctional right ventricular
      outflow tract (RVOT) with right ventricle to pulmonary artery (PA) obstruction.
      The use of the Melody valve for haemodynamically significant isolated pulmonary
      regurgitation has not been evaluated. AIM: We evaluated the outcomes of Melody
      valve insertion in patients with a large patched RVOT. METHODS: We analysed
      procedural and short-term outcomes data from 13 patients who underwent Melody
      valve implantation for a large RVOT with significant pulmonary regurgitation as
      the primary lesion. RVOT preparation was done in all patients using the Russian
      dolls technique and/or the PA jailing technique. Melody valve insertion was
      performed concomitantly in 10 patients and after 1 to 3 months in three patients.
      RESULTS: All procedures were successful. The mean follow-up period was 30 +/- 4
      months after the procedure. There was no incidence of stent fracture, migration
      or embolization. Only one patient who underwent the jailing technique developed a
      significant paraprosthetic leak and is scheduled for redilatation of the Melody
      valve. CONCLUSIONS: Careful patient selection, balloon sizing and RVOT
      preparation with prestenting using the Russian dolls technique and/or the PA
      jailing technique are required to modify the RVOT for transcatheter valve
      implantation. Short-term follow-up showed competent valves with no stent fracture
      or migration and appears promising. Wider experience with long-term outcomes may
      be required to standardize the procedure in such a subset of patients.

PMID- 22958884
TI  - Regional system of care for ST-segment elevation myocardial infarction in the
      Northern Alps: a controlled pre- and postintervention study.
AB  - BACKGROUND: Regionalization of care for ST-segment elevation myocardial
      infarction (STEMI) has been advocated, although its effect on processes of care
      and clinical outcomes remains uncertain. AIM: To assess the impact of a regional
      system of care on provision of reperfusion therapy for STEMI patients relative to
      control hospitals. METHODS: We analysed the original data from two nationwide
      prospective cohort studies conducted in 2000 and 2005, respectively. Overall, 160
      hospitals participated in both studies, including seven hospitals involved in a
      regional system of care implemented in the Northern Alps in 2002 and 153 control
      hospitals located in other French areas. RESULTS: A total of 102 and 2377 STEMI
      patients were enrolled in Northern Alps and control hospitals, respectively.
      Overall, patients enrolled in 2005 were more likely to receive any reperfusion
      therapy (60% vs 52%; P < 0.001), prehospital fibrinolysis (33% vs 15%; P <
      0.001), and primary percutaneous coronary intervention (32% vs 26%; P < 0.001)
      than those enrolled in 2000. However, the regional system of care was associated
      with a larger absolute change in the use of prehospital fibrinolysis (45.0 vs
      17.0; P = 0.02) and rescue or early routine coronary angiography or intervention
      after fibrinolysis (35.3 vs 15.2; P = 0.01). Patients enrolled in 2005 had lower
      adjusted hazard ratios for death (0.70, 95% confidence interval 0.57-0.87; P =
      0.001), with no significant interaction between study groups. CONCLUSION:
      Regionalization of care for STEMI patients improves access to reperfusion
      therapy, although its impact on clinical outcomes deserves further study.

PMID- 22958885
TI  - Accuracy of multislice computed tomography in the preoperative assessment of
      coronary disease in patients scheduled for heart valve surgery.
AB  - BACKGROUND: Coronary angiography (CA), an invasive and expensive procedure, is
      still recommended in most patients referred for elective valve surgery.
      Multislice computed tomography (MSCT) is a promising alternative technique to
      rule out significant coronary artery lesions. AIM: To evaluate MSCT in detecting
      significant coronary artery lesions in patients referred for elective valve
      surgery. METHODS: Between August 2007 and December 2010, patients referred for
      elective valve surgery were identified prospectively and underwent 64-slice MSCT
      and CA. We compared significant coronary stenoses, defined as a reduction of
      luminal diameter >= 50%, to establish the diagnostic accuracy of MSCT. All
      coronary segments were analysed and uninterpretable lesions were scored positive.
      RESULTS: Forty-eight patients were included (62.5% male; mean age 65 +/- 12
      years), the majority had aortic insufficiency (37.7%) or aortic stenosis (32.0%).
      The prevalence of significant coronary artery stenoses was 27.1%. The
      sensitivity, specificity, positive and negative predictive values of MSCT were
      77%, 89%, 71% and 91%, respectively, in a patient-based analysis; 82%, 86%, 64%
      and 94% in a revascularization-based analysis; 67%, 94%, 52% and 97% in a vessel
      based analysis; and 65%, 98%, 52% and 99% in a segment-based analysis. Overall,
      CA could have been avoided in 65% of patients. CONCLUSION: In patients referred
      for elective valve surgery, MSCT had a high diagnostic accuracy to rule out
      significant coronary stenoses. However, larger multicenter studies in an
      unselected population of patients are needed to determine its place within the
      range of diagnostic tool in the preoperative assessment of valvular heart
      disease.

PMID- 22958886
TI  - The role of echocardiography in the assessment of right ventricular systolic
      function in patients with transposition of the great arteries and atrial
      redirection.
AB  - BACKGROUND: Although dysfunction of the systemic right ventricle (RV) in patients
      with complete transposition of the great arteries (TGA) after atrial redirection
      by Mustard or Senning procedures is well recognized, there are few data on
      systemic RV geometry and function. Echocardiography is a widely available imaging
      technique that is particularly suitable for clinical follow-up because of its non
      invasive nature, low cost and lack of ionizing radiation. AIM: To examine the
      feasibility and variability of transthoracic echocardiography variables in the
      assessment of the systemic RV. METHODS: Multivariable transthoracic
      echocardiographic analysis, including assessment of global function variables (RV
      ejection fraction [RVEF; Simpson's method], RV fractional shortening [RVFS] and
      dP/dt), longitudinal function variables (tricuspid annular plane systolic
      excursion [TAPSE], peak systolic velocity at the junction of the RV free wall and
      the tricuspid annulus, assessed with pulsed tissue Doppler imaging [S' TDI]),
      tricuspid regurgitation and asynchrony, was performed in 35 consecutive patients
      with TGA after atrial redirection. Functional variables were compared with
      magnetic resonance imaging (MRI). Inter- and intraobserver echocardiographic
      analysis variability was assessed in ten randomly selected cases. RESULTS: Global
      and longitudinal function variables were not correlated with RVEF calculated by
      MRI, except for S' TDI, which was weakly correlated (P = 0.02, r = 0.37).
      Asynchrony assessment was feasible in all patients. Inter- and intraobserver
      echocardiographic analysis variability was high for RVEF, RVFS and dP/dt (> 10%),
      and low for TAPSE and S' TDI (5%). CONCLUSION: Owing to geometric changes,
      presumed contractility pattern shift and retrosternal position, conventional
      echocardiographic variables are not relevant for RV function assessment.
      Assessment of asynchrony and tricuspid regurgitation is easily feasible in
      routine practice and highly reproducible. Echocardiography does not permit
      complete assessment of the systemic RV after atrial redirection but is fully
      complementary with MRI and should not be abandoned. Future improvements in
      transducers and dedicated software should permit major improvements in the near
      future.

PMID- 22958887
TI  - Cardiac rhabdomyomas in tuberous sclerosis patients: a case report and review of
      the literature.
AB  - Rhabdomyomas are the most common benign cardiac tumours. They are often
      associated with tuberous sclerosis and can be diagnosed antenatally and
      postnatally by echocardiography. Rhabdomyomas tend to regress spontaneously and
      are not usually operated upon, unless they become obstructive or cause severe
      arrhythmias. We describe the case of a child with tuberous sclerosis who was
      admitted for the resection of a subependymal giant cell astrocytoma, in whom
      cardiac rhabdomyomas in the right ventricular outflow tract were diagnosed. These
      two kinds of tumours are well known in the setting of tuberous sclerosis.

PMID- 22958888
TI  - Remote magnetic navigation and arrhythmia ablation.
AB  - Radiofrequency treatment is the first-choice treatment for arrhythmias, in
      particular complex arrhythmias and especially atrial fibrillation, due to the
      greater benefit/risk ratio compared with antiarrhythmic drugs. However, complex
      arrhythmias such as atrial fibrillation require long procedures with additional
      risks such as X-ray exposure or serious complications including tamponade. Given
      this context, robotic magnetic navigation is a technique well suited to the
      treatment of complex arrhythmias, on account of its efficacy and reliability, the
      significant reduction in X-ray exposure for both patient and operator, and the
      very low risk of perforation. As ongoing developments will likely improve results
      and procedure times, this technology will become one of the most advanced for
      treating arrhythmias.

PMID- 22958889
TI  - Prophylaxis of infective endocarditis in patients with congenital heart disease
      in the context of recent modified guidelines.
AB  - Infective endocarditis (IE) is a life-threatening complication that may impair
      significantly the long-term prognosis of patients with cardiac disease. The
      profile of IE has changed over recent decades, with a decreasing prevalence of
      rheumatic fever and increasing survival of patients with congenital heart disease
      (CHDs). Given the high rates of morbidity and mortality, and based on previous
      experimental studies, antibiotic prevention of IE has long been recommended for
      at-risk groups. Serial revised guidelines for prophylaxis have been published
      over the years. The most recent recommendations differ dramatically from previous
      guidelines and provide new insights into the prophylaxis of IE. Emphasis is put
      on oral activities (particularly brushing teeth) as both buccal and skin hygiene
      may present the greatest threats for individuals at-risk of IE. Significant
      limitations in both at-risk patients and procedures result in a potential and
      substantial change in the practice of clinicians and raise concerns about the
      safety and reliability of these new recommendations for patients with CHD.

PMID- 22958890
TI  - Coronary microvasculopathy and intracardiac thrombosis in antiphospholipid
      syndrome.

PMID- 22958891
TI  - Primary lymphoma of the heart.

PMID- 22958892
TI  - Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility
      of human cardiac alpha-tropomyosin.
AB  - alpha-Tropomyosin (alphaTm) is central to Ca(2+)-regulation of cardiac muscle
      contraction. The familial hypertrophic cardiomyopathy mutation alphaTm E180G
      enhances Ca(2+)-sensitivity in functional assays. To investigate the molecular
      basis, we imaged single molecules of human cardiac alphaTm E180G by direct probe
      atomic force microscopy. Analyses of tangent angles along molecular contours
      yielded persistence length corresponding to ~35% increase in flexibility compared
      to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to
      end length distributions to the worm-like chain model. This marked increase in
      flexibility can significantly impact systolic and possibly diastolic phases of
      cardiac contraction, ultimately leading to hypertrophy.

PMID- 22958893
TI  - miR-518b is down-regulated, and involved in cell proliferation and invasion by
      targeting Rap1b in esophageal squamous cell carcinoma.
AB  - MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene
      expression at the post-transcriptional levels. Recent studies show that miRNAs
      may function as oncogenes or tumor suppressor genes. In this study, we
      demonstrated that miR-518b was down-regulated in esophageal squamous cell
      carcinoma (ESCC) tissues and correlated with metastasis and survival. miR-518b
      suppressed the proliferation by inducing apoptosis and repressed the invasion in
      ESCC cells, but had no effect on the cell cycle. Furthermore, Rap1b was revealed
      to be directly regulated by miR-518b. These findings indicate that miR-518b may
      function as a tumor suppressor by targeting Rap1b in the development of ESCC and
      has important clinical and prognostic value.

PMID- 22958894
TI  - Cough variant asthma and atopic cough.
AB  - Chronic cough has been reported to be the fifth most common complaint seen by
      primary care physicians in the world, the third in Italy. Chronic cough in non
      smoking, non-treated with ACE-inhibitor adults with normal chest radiogram could
      be a symptom of asthma and can be sub-classified into: cough-variant asthma,
      atopic cough, and eosinophilic bronchitis. This review discusses the differential
      diagnosis of these three disorders.

PMID- 22958895
TI  - A phylogenomic analysis of Escherichia coli / Shigella group: implications of
      genomic features associated with pathogenicity and ecological adaptation.
AB  - BACKGROUND: The Escherichia coli species contains a variety of commensal and
      pathogenic strains, and its intraspecific diversity is extraordinarily high. With
      the availability of an increasing number of E. coli strain genomes, a more
      comprehensive concept of their evolutionary history and ecological adaptation can
      be developed using phylogenomic analyses. In this study, we constructed two types
      of whole-genome phylogenies based on 34 E. coli strains using collinear genomic
      segments. The first phylogeny was based on the concatenated collinear regions
      shared by all of the studied genomes, and the second phylogeny was based on the
      variable collinear regions that are absent from at least one genome. Intuitively,
      the first phylogeny is likely to reveal the lineal evolutionary history among
      these strains (i.e., an evolutionary phylogeny), whereas the latter phylogeny is
      likely to reflect the whole-genome similarities of extant strains (i.e., a
      similarity phylogeny). RESULTS: Within the evolutionary phylogeny, the strains
      were clustered in accordance with known phylogenetic groups and phenotypes. When
      comparing evolutionary and similarity phylogenies, a concept emerges that
      Shigella may have originated from at least three distinct ancestors and evolved
      into a single clade. By scrutinizing the properties that are shared amongst
      Shigella strains but missing in other E. coli genomes, we found that the common
      regions of the Shigella genomes were mainly influenced by mobile genetic
      elements, implying that they may have experienced convergent evolution via
      horizontal gene transfer. Based on an inspection of certain key branches of
      interest, we identified several collinear regions that may be associated with the
      pathogenicity of specific strains. Moreover, by examining the annotated genes
      within these regions, further detailed evidence associated with pathogenicity was
      revealed. CONCLUSIONS: Collinear regions are reliable genomic features used for
      phylogenomic analysis among closely related genomes while linking the genomic
      diversity with phenotypic differences in a meaningful way. The pathogenicity of a
      strain may be associated with both the arrival of virulence factors and the
      modification of genomes via mutations. Such phylogenomic studies that compare
      collinear regions of whole genomes will help to better understand the evolution
      and adaptation of closely related microbes and E. coli in particular.

PMID- 22958896
TI  - Economics and resourcing of complex healthcare systems.
AB  - With rapid increases in healthcare spending over recent years, health economic
      evaluation might be thought to be increasing in importance to decision-makers.
      Such evaluations are designed to inform the efficient management of healthcare
      resources. However, research into health policy decisions often report, at best,
      moderate use of economic evaluation information, especially at the local level of
      administration. Little attention seems to have been given to the question of why
      economic evaluations have been underused and why they may yield different results
      in different contexts. There are many barriers to applying economic evaluations
      in situations which combine complexity with uncertainty. These barriers call for
      innovative and creative responses to economic evaluation of healthcare
      interventions. One response is to view economic evaluations in the context of
      complex adaptive systems theory. Such theory offers a conceptual framework that
      takes into account contextual factors, multiple input and output, multiple
      perspectives and uncertainty involved in healthcare interventions. This article
      illustrates how complexity theory can enrich and broaden policy-makers'
      understanding of why economic evaluations have not always been as successful as
      health economists would have hoped. It argues for health economists to emphasise
      contextual knowledge and relativist understanding of decision contexts rather
      than seeking more technically sound evidence-based reviews including economic
      evaluations.

PMID- 22958897
TI  - COPD, smoking behaviour, and the importance of teachers as role-models for
      adolescents.

PMID- 22958898
TI  - [Hemophagocytic syndrome due to Herpes simplex virus after hysteroscopy].
AB  - Hemophagocytic syndrome is an uncommon but life-threatening complication of
      Herpes simplex virus type 1 or 2 infection. Diagnosis is difficult to establish
      given the low specificity of clinical and biological signs.

PMID- 22958899
TI  - Genetic risk factors for type 2 diabetes: a trans-regulatory genetic
      architecture?
AB  - To date, 68 loci have been associated with type 2 diabetes (T2D) or glucose
      homeostasis traits. We report here the results of experiments aimed at
      functionally characterizing the SNPs replicated for T2D and glucose traits. We
      sought to determine whether these loci were associated with transcript levels in
      adipose, muscle, liver, lymphocytes, and pancreatic beta-cells. We found an
      excess of trans, rather than cis, associations among these SNPs in comparison to
      what was expected in adipose and muscle. Among transcripts differentially
      expressed (FDR < 0.05) between muscle or adipose cells of insulin-sensitive
      individuals and those of insulin-resistant individuals (matched on BMI), trans
      regulated transcripts, in contrast to the cis-regulated ones, were enriched. The
      paucity of cis associations with transcripts was confirmed in a study of liver
      transcriptome and was further supported by an analysis of the most detailed
      transcriptome map of pancreatic beta-cells. Relative to location- and allele
      frequency-matched random SNPs, both the 68 loci and top T2D-associated SNPs from
      two large-scale genome-wide studies were enriched for trans eQTLs in adipose and
      muscle but not in lymphocytes. Our study suggests that T2D SNPs have broad
      reaching and tissue-specific effects that often extend beyond local transcripts
      and raises the question of whether patterns of cis or trans transcript regulation
      are a key feature of the architecture of complex traits.

PMID- 22958900
TI  - HYST: a hybrid set-based test for genome-wide association studies, with
      application to protein-protein interaction-based association analysis.
AB  - The extended Simes' test (known as GATES) and scaled chi-square test were
      proposed to combine a set of dependent genome-wide association signals at
      multiple single-nucleotide polymorphisms (SNPs) for assessing the overall
      significance of association at the gene or pathway levels. The two tests use
      different strategies to combine association p values and can outperform each
      other when the number of and linkage disequilibrium between SNPs vary. In this
      paper, we introduce a hybrid set-based test (HYST) combining the two tests for
      genome-wide association studies (GWASs). We describe how HYST can be used to
      evaluate statistical significance for association at the protein-protein
      interaction (PPI) level in order to increase power for detecting disease
      susceptibility genes of moderate effect size. Computer simulations demonstrated
      that HYST had a reasonable type 1 error rate and was generally more powerful than
      its parents and other alternative tests to detect a PPI pair where both genes are
      associated with the disease of interest. We applied the method to three complex
      disease GWAS data sets in the public domain; the method detected a number of
      highly connected significant PPI pairs involving multiple confirmed disease
      susceptibility genes not found in the SNP- and gene-based association analyses.
      These results indicate that HYST can be effectively used to examine a collection
      of predefined SNP sets based on prior biological knowledge for revealing
      additional disease-predisposing genes of modest effects in GWASs.

PMID- 22958901
TI  - Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study
      cohorts.
AB  - Rare sarcomere protein variants cause dominant hypertrophic and dilated
      cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes
      are associated with cardiac morphology and function in the community, we
      sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson
      Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more
      rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic
      sarcomere variants was 0.6%, twice the previous estimates; however, only four of
      the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy.
      Rare sarcomere variants were associated with an increased risk for adverse
      cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that
      cardiovascular risk assessment in the general population can benefit from rare
      variant analysis.

PMID- 22958902
TI  - Loss of SUFU function in familial multiple meningioma.
AB  - Meningiomas are the most common primary tumors of the CNS and account for up to
      30% of all CNS tumors. An increased risk of meningiomas has been associated with
      certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but
      no gene defects predisposing to isolated familial meningiomas have thus far been
      identified. Here, we report on a family of five meningioma-affected siblings,
      four of whom have multiple tumors. No NF2 mutations were identified in the
      germline or tumors. We combined genome-wide linkage analysis and exome
      sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU,
      a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family.
      The variation was not present in healthy controls, and all seven meningiomas
      analyzed displayed loss of the wild-type allele according to the classic two-hit
      model for tumor-suppressor genes. In silico modeling predicted the variant to
      affect the tertiary structure of the protein, and functional analyses showed that
      the activity of the altered SUFU was significantly reduced and therefore led to
      dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene
      previously associated with childhood medulloblastoma predisposition. Our genetic
      and functional analyses indicate that germline mutations in SUFU also predispose
      to meningiomas, particularly to multiple meningiomas. It is possible that other
      genic mutations resulting in aberrant activation of the Hh pathway might underlie
      meningioma predisposition in families with an unknown etiology.

PMID- 22958903
TI  - Exome sequencing and functional validation in zebrafish identify GTDC2 mutations
      as a cause of Walker-Warburg syndrome.
AB  - Whole-exome sequencing (WES), which analyzes the coding sequence of most
      annotated genes in the human genome, is an ideal approach to studying fully
      penetrant autosomal-recessive diseases, and it has been very powerful in
      identifying disease-causing mutations even when enrollment of affected
      individuals is limited by reduced survival. In this study, we combined WES with
      homozygosity analysis of consanguineous pedigrees, which are informative even
      when a single affected individual is available, to identify genetic mutations
      responsible for Walker-Warburg syndrome (WWS), a genetically heterogeneous
      autosomal-recessive disorder that severely affects the development of the brain,
      eyes, and muscle. Mutations in seven genes are known to cause WWS and explain 50%
      60% of cases, but multiple additional genes are expected to be mutated because
      unexplained cases show suggestive linkage to diverse loci. Using WES in
      consanguineous WWS-affected families, we found multiple deleterious mutations in
      GTDC2 (also known as AGO61). GTDC2's predicted role as an uncharacterized
      glycosyltransferase is consistent with the function of other genes that are known
      to be mutated in WWS and that are involved in the glycosylation of the
      transmembrane receptor dystroglycan. Therefore, to explore the role of GTDC2 loss
      of function during development, we used morpholino-mediated knockdown of its
      zebrafish ortholog, gtdc2. We found that gtdc2 knockdown in zebrafish replicates
      all WWS features (hydrocephalus, ocular defects, and muscular dystrophy),
      strongly suggesting that GTDC2 mutations cause WWS.

PMID- 22958904
TI  - VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland
      families.
AB  - Our group previously described and mapped to chromosomal region 12p13 a form of
      dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland
      (Canada) families. This report identifies vesicle-associated membrane protein 1
      (VAMP1), which encodes a critical protein for synaptic exocytosis, as the
      responsible gene. In total, 50 affected individuals from these families and three
      independent probands from Ontario (Canada) share the disease phenotype together
      with a disruptive VAMP1 mutation that affects a critical donor site for the
      splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1
      isoform (VAMP1A) expressed in the nervous system, thus highlighting an
      association between the well-studied VAMP1 and a neurological disorder. Given the
      variable phenotype seen in the affected individuals examined here, we believe
      that VAMP1 should be tested for mutations in patients with either ataxia or
      spastic paraplegia.

PMID- 22958905
TI  - Questioning the limits of genomic privacy.

PMID- 22958907
TI  - Cardiac dysfunction in cirrhosis is not associated with the severity of liver
      disease.
AB  - BACKGROUND: Cirrhotic cardiomiopathy is described as the presence of cardiac
      dysfunction in cirrhotic patients. The aim of the study was to investigate
      factors associated with cardiac dysfunction in cirrhotic patients. PATIENTS AND
      METHODS: Seventy-four cirrhotic patients and twenty-six controls performed a
      conventional echocardiography and Tissue Doppler Imaging (TDI) for systolic and
      diastolic function. Results were analyzed by using the Guidelines of American
      Society of Echocardiography. RESULTS: In patients with cirrhosis, left
      ventricular end-diastolic diameter was increased (p<0.001) , peak systolic
      velocities were decreased (11.3+/-2.7 vs 13.9+/-1.4cm/s; p<0.001) and left atrial
      volumes were increased (32.7+/-8.3 vs 24+/-8.5ml, p<0.001) as well as cardiac
      mass (90.6+/-23 vs 70.5+/-22g/m(2), p<0.001). Forty-seven cirrhotic patients
      (64%) showed diastolic dysfunction at rest: grade I in 37 and grade II in 10
      patients. Systolic and/or diastolic dysfunction were not influenced by a more
      severe liver impairment. Diastolic dysfunction was more prevalent in patients
      with ascites vs those without (77% vs 56%; p=0.04). CONCLUSION: A mild diastolic
      dysfunction at rest is frequent in cirrhotic patients but cardiac load conditions
      are confounding factors in this diagnosis. We did not identify an association
      between severity of liver disease and cardiac dysfunction.

PMID- 22958908
TI  - Alternative site pacing: accessing normal precordial activation: is it possible?
AB  - Pacemaker implantation is necessary in patients with symptomatic bradycardia. The
      right ventricular (RV) apex is the traditional pacing site because of its ease of
      access with simple and reliable technology. However, by forcing mechanical
      desynchronization, this may induce adverse effects, especially in heart failure
      patients. To avoid these problems, alternative sites for pacing have been
      explored with the idea of preserving normal ventricular activation. The His
      bundle is an obvious target, and results are promising, but permanent pacing is
      fraught with technical difficulties. Assessment of the RV septum and outflow
      tract has generated inconclusive results. Significant limitations to trials to
      date are inconsistency of electrode deployment to selected regions (themselves
      vaguely defined), and the unverified assumption that a single RV region will
      yield the desired ventricular activation pattern in every patient. Notably, an
      electrical measure of satisfactory lead positioning has been lacking, despite the
      fact that QRS abbreviation is associated with improved hemodynamics.
      Nevertheless, pooled trial results suggest benefits, which tend to accrue with
      time, especially in patients with LV dysfunction, i.e., the group vulnerable to
      RV apical pacing. Can results with alternate site pacing be improved? The
      location of any "sweet spot" may be variable among individuals (or even non
      existent), requiring identification by its electrical effect to guide electrode
      deployment, accurately. The selected alternate sites need to avoid delayed
      transseptal activation associated with RV apical pacing (similar to LBBB) and
      result in rapid LV depolarization. However, distinctions may not be binary. For
      example, apical pacing exerts diverse actions in different individuals, not all
      of which are deleterious. A relatively underlooked aspect is that both apical and
      alternate RV site pacing may affect right ventricular activation and thus
      interventricular dyssynchrony, interfering with ventricular coupling and pump
      function. Most of these effects are not evident on surface QRS, which is an
      indirect approximation of electrical action. This may be elaborated with more
      detailed mapping, e.g., non-invasively with electrocardiographic imaging. In the
      future, pacing site selection individualized according to detailed biventricular
      activation effects may enhance outcomes with alternate site pacing.

PMID- 22958909
TI  - T-wave alternans: lessons learned from a biophysical ECG model.
AB  - T-wave alternans (TWA) is an alteration of the ECG T-wave which repeats every
      other beat. An alternating pattern has been also observed at myocytes level,
      involving both action potential duration and morphology (mainly in phases 2 and
      3). While this might happen in a specific region (i.e., myocardial ischemia), it
      can also involve the entire myocardium. It is still unclear how alternations at
      the myocytes level are reflected on surface ECG modification of T-waves,
      especially when in vivo human hearts are considered. We have recently proposed a
      simple stochastic model of ventricular repolarization (IEEE Trans. Biomed. Eng.,
      2011), which takes into account both repolarization heterogeneity across the
      myocardium as well as random beat-to-beat variations in cells' activity. In this
      work, we generalized that model incorporating a term which describes myocytes
      alternans related to T-wave variability. Starting from the model and using the
      electrophysiological formulation developed by van Oosterom, we derived an
      analytical formula relating surface ECG to variations at the myocytes' level.
      Several theoretical results were then obtained. First, temporal small random
      variations in repolarization heterogeneity affect the precision of TWA estimates
      in a significant way. Second, TWA theoretically differs across leads, but
      multilead configuration can be used to reduce the effect of noise. Finally, the
      dependency between TWA and T-wave amplitude was analyzed.

PMID- 22958910
TI  - Effects of indoor air pollution on respiratory symptoms of non-smoking women in
      Nis, Serbia.
AB  - RATIONALE: The aim of this study was to determine the effects of indoor air
      pollution exposure on respiratory symptoms and illnesses in non-smoking women in
      Nis, Serbia. MATERIALS AND METHODS: The study was carried out in 1,082 never
      smoking females, aged 20-40 years, who were not occupationally exposed to indoor
      air pollution. The prevalence of respiratory symptoms and illnesses was assessed
      using the American Thoracic Society questionnaires. Multivariate methods were
      used in the analysis. RESULTS: A strong association was found between respiratory
      symptoms and indoor air pollution. The associations between home dampness and
      sinusitis and bronchitis were also found to be statistically significant.
      CONCLUSIONS: Indoor air pollution exposure is an important risk factor for
      respiratory symptoms and illnesses in non-smoking women in Nis, Serbia.

PMID- 22958911
TI  - Impact of a hospital-wide hand hygiene promotion strategy on healthcare
      associated infections.
AB  - BACKGROUND: During the Severe Acute Respiratory Syndrome (SARS) outbreak, high
      compliance in healthcare workers to hand hygiene was primarily driven by fear.
      However, the post-SARS period confirmed that this practice was not sustainable.
      At the Singapore General Hospital, a 1,600-bedded acute tertiary care hospital,
      the hand hygiene program was revised in early 2007 following Singapore's signing
      of the pledge to the World Health Organization (WHO) "Clean Care is Safer Care"
      program. FINDINGS: A multi-prong approach was used in designing the hand hygiene
      program. This included system change; training and education; evaluation and
      feedback; reminders in the workplace; and institutional safety climate. Hand
      hygiene compliance rate improved from 20% (in January 2007) to 61% (2010).
      Improvement was also seen annually in the compliance to each of the 5 moments as
      well as in all staff categories. Healthcare-associated MRSA infections were
      reduced from 0.6 (2007) to 0.3 (2010) per 1000 patient-days. CONCLUSIONS:
      Leadership's support of the program evidenced through visible leadership
      presence, messaging and release of resources is the key factor in helping to make
      the program a true success. The hospital was recognised as a Global Hand Hygiene
      Expert Centre in January 2011. The WHO multi-prong interventions work in
      improving compliance and reducing healthcare associated infections.

PMID- 22958913
TI  - Duration of in-hospital resuscitation: when to call time?

PMID- 22958912
TI  - Duration of resuscitation efforts and survival after in-hospital cardiac arrest:
      an observational study.
AB  - BACKGROUND: During in-hospital cardiac arrests, how long resuscitation attempts
      should be continued before termination of efforts is unknown. We investigated
      whether duration of resuscitation attempts varies between hospitals and whether
      patients at hospitals that attempt resuscitation for longer have higher survival
      rates than do those at hospitals with shorter durations of resuscitation efforts.
      METHODS: Between 2000 and 2008, we identified 64,339 patients with cardiac
      arrests at 435 US hospitals within the Get With The Guidelines-Resuscitation
      registry. For each hospital, we calculated the median duration of resuscitation
      before termination of efforts in non-survivors as a measure of the hospital's
      overall tendency for longer attempts. We used multilevel regression models to
      assess the association between the length of resuscitation attempts and risk
      adjusted survival. Our primary endpoints were immediate survival with return of
      spontaneous circulation during cardiac arrest and survival to hospital discharge.
      FINDINGS: 31,198 of 64,339 (48.5%) patients achieved return of spontaneous
      circulation and 9912 (15.4%) survived to discharge. For patients achieving return
      of spontaneous circulation, the median duration of resuscitation was 12 min (IQR
      6-21) compared with 20 min (14-30) for non-survivors. Compared with patients at
      hospitals in the quartile with the shortest median resuscitation attempts in non
      survivors (16 min [IQR 15-17]), those at hospitals in the quartile with the
      longest attempts (25 min [25-28]) had a higher likelihood of return of
      spontaneous circulation (adjusted risk ratio 1.12, 95% CI 1.06-1.18; p<0.0001)
      and survival to discharge (1.12, 1.02-1.23; 0.021). INTERPRETATION: Duration of
      resuscitation attempts varies between hospitals. Although we cannot define an
      optimum duration for resuscitation attempts on the basis of these observational
      data, our findings suggest that efforts to systematically increase the duration
      of resuscitation could improve survival in this high-risk population. FUNDING:
      American Heart Association, Robert Wood Johnson Foundation Clinical Scholars
      Program, and the National Institutes of Health.

PMID- 22958915
TI  - A role for dicer in aging and stress survival.
AB  - The link between aging and stress resistance is well established, but the nature
      of this relationship and which mechanisms are shared is still unknown. Mori et
      al. (2012) demonstrate that microRNA processing, specifically in adipose tissues,
      is a major component in aging and stress survival.

PMID- 22958914
TI  - A molecular computational model improves the preoperative diagnosis of thyroid
      nodules.
AB  - BACKGROUND: Thyroid nodules with indeterminate cytological features on fine
      needle aspiration (FNA) cytology have a 20% risk of thyroid cancer. The aim of
      the current study was to determine the diagnostic utility of an 8-gene assay to
      distinguish benign from malignant thyroid neoplasm. METHODS: The mRNA expression
      level of 9 genes (KIT, SYNGR2, C21orf4, Hs.296031, DDI2, CDH1, LSM7, TC1, NATH)
      was analysed by quantitative PCR (q-PCR) in 93 FNA cytological samples. To
      evaluate the diagnostic utility of all the genes analysed, we assessed the area
      under the curve (AUC) for each gene individually and in combination. BRAF exon 15
      status was determined by pyrosequencing. An 8-gene computational model (Neural
      Network Bayesian Classifier) was built and a multiple-variable analysis was then
      performed to assess the correlation between the markers. RESULTS: The AUC for
      each significant marker ranged between 0.625 and 0.900, thus all the significant
      markers, alone and in combination, can be used to distinguish between malignant
      and benign FNA samples. The classifier made up of KIT, CDH1, LSM7, C21orf4, DDI2,
      TC1, Hs.296031 and BRAF had a predictive power of 88.8%. It proved to be useful
      for risk stratification of the most critical cytological group of the
      indeterminate lesions for which there is the greatest need of accurate diagnostic
      markers. CONCLUSION: The genetic classification obtained with this model is
      highly accurate at differentiating malignant from benign thyroid lesions and
      might be a useful adjunct in the preoperative management of patients with thyroid
      nodules.

PMID- 22958916
TI  - A radical view of pathological vasculature.
AB  - Striking results reported by Okuno et al. (2012) in the July issue of Nature
      Medicine show that the ataxia telangiectasia mutated (ATM) kinase counteracts
      excessive oxygen radical production in immature angiogenic blood vessels. Its
      deletion results in activation of the mitogen-activated protein kinase p38alpha
      and arrest of pathological angiogenesis.

PMID- 22958917
TI  - Stem cells bleed into brown fat.
AB  - The cellular origins and molecular determinants of brown adipose tissue (BAT) are
      the focus of renewed attention. Serendipitous studies examining hematopoiesis in
      human pluripotent stem cell cultures (Nishio et al., 2012, in this issue of Cell
      Metabolism) now identify cytokines capable of inducing BAT differentiation from
      these human stem cells and suggest a link between BAT and blood cells.

PMID- 22958918
TI  - Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3.
AB  - Chronic activation of mammalian target of rapamycin complex 1 (mTORC1) and p70 S6
      kinase (S6K) in response to hypernutrition contributes to obesity-associated
      metabolic pathologies, including hepatosteatosis and insulin resistance. Sestrins
      are stress-inducible proteins that activate AMP-activated protein kinase (AMPK)
      and suppress mTORC1-S6K activity, but their role in mammalian physiology and
      metabolism has not been investigated. We show that Sestrin2--encoded by the Sesn2
      locus, whose expression is induced upon hypernutrition--maintains metabolic
      homeostasis in liver of obese mice. Sesn2 ablation exacerbates obesity-induced
      mTORC1-S6K activation, glucose intolerance, insulin resistance, and
      hepatosteatosis, all of which are reversed by AMPK activation. Furthermore,
      concomitant ablation of Sesn2 and Sesn3 provokes hepatic mTORC1-S6K activation
      and insulin resistance even in the absence of nutritional overload and obesity.
      These results demonstrate an important homeostatic function for the stress
      inducible Sestrin protein family in the control of mammalian lipid and glucose
      metabolism.

PMID- 22958919
TI  - Role of microRNA processing in adipose tissue in stress defense and longevity.
AB  - Excess adipose tissue is associated with metabolic disease and reduced life span,
      whereas caloric restriction decreases these risks. Here we show that as mice age,
      there is downregulation of Dicer and miRNA processing in adipose tissue resulting
      in decreases of multiple miRNAs. A similar decline of Dicer with age is observed
      in C. elegans. This is prevented in both species by caloric restriction.
      Decreased Dicer expression also occurs in preadipocytes from elderly humans and
      can be produced in cells by exposure to oxidative stress or UV radiation.
      Knockdown of Dicer in cells results in premature senescence, and fat-specific
      Dicer knockout renders mice hypersensitive to oxidative stress. Finally, Dicer
      loss-of-function mutations in worms reduce life span and stress tolerance, while
      intestinal overexpression of Dicer confers stress resistance. Thus, regulation of
      miRNA processing in adipose-related tissues plays an important role in longevity
      and the ability of an organism to respond to environmental stress and age-related
      disease.

PMID- 22958920
TI  - BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher
      insulin sensitivity, glucose usage, and decreased inflammatory response.
AB  - Studying ciliopathies, like the Bardet-Biedl syndrome (BBS), allow the
      identification of signaling pathways potentially involved in common diseases,
      sharing phenotypic features like obesity or type 2 diabetes. Given the close
      association between obesity and insulin resistance, obese BBS patients would be
      expected to be insulin resistant. Surprisingly, we found that a majority of obese
      BBS patients retained normal glucose tolerance and insulin sensitivity. Patient's
      adipose tissue biopsies revealed upregulation of adipogenic genes and decrease of
      inflammatory mediators. In vitro studies on human primary mesenchymal stem cells
      (MSCs) showed that BBS12 inactivation facilitated adipogenesis, increased insulin
      sensitivity, and glucose utilization. We generated a Bbs12(-/-) mouse model to
      assess the impact of Bbs12 inactivation on adipocyte biology. Despite increased
      obesity, glucose tolerance was increased with specific enhanced insulin
      sensitivity in the fat. This correlated with an active recruitment of MSCs
      resulting in adipose tissue hyperplasia and decreased in inflammation.

PMID- 22958921
TI  - betaKlotho is required for fibroblast growth factor 21 effects on growth and
      metabolism.
AB  - Fibroblast growth factor 21 (FGF21) is a fasting-induced hepatokine that has
      potent pharmacologic effects in mice, which include improving insulin sensitivity
      and blunting growth. The single-transmembrane protein betaKlotho functions as a
      coreceptor for FGF21 in vitro. To determine if betaKlotho is required for FGF21
      action in vivo, we generated whole-body and adipose tissue-selective betaKlotho
      knockout mice. All of the effects of FGF21 on growth and metabolism were lost in
      whole-body betaKlotho-knockout mice. Selective elimination of betaKlotho in
      adipose tissue blocked the acute insulin-sensitizing effects of FGF21. Taken
      together, these data demonstrate that betaKlotho is essential for FGF21 activity
      and that betaKlotho in adipose tissue contributes to the beneficial metabolic
      actions of FGF21.

PMID- 22958922
TI  - Production of functional classical brown adipocytes from human pluripotent stem
      cells using specific hemopoietin cocktail without gene transfer.
AB  - Brown adipose tissue is attracting much attention due to its antiobestic effects;
      however, its development and involvement in metabolic improvement remain elusive.
      Here we established a method for a high-efficiency (>90%) differentiation of
      human pluripotent stem cells (hPSCs) into functional classical brown adipocytes
      (BAs) using specific hemopoietin cocktail (HC) without exogenous gene transfer.
      BAs were not generated without HC, and lack of a component of HC induced white
      adipocyte (WA) marker expressions. hPSC-derived BA (hPSCdBA) showed respiratory
      and thermogenic activation by beta-adrenergic receptor (AdrRbeta) stimuli and
      augmented lipid and glucose tolerance, whereas human multipotent stromal cell
      derived WA (hMSCdWA) improved lipid but inhibited glucose metabolism.
      Cotransplantation of hPSCdBA normalized hMSCdWA-induced glucose intolerance.
      Surprisingly, hPSCdBAs expressed various hemopoietin genes, serving as stroma for
      myeloid progenitors. Moreover, AdrRbeta stimuli enhanced recovery from
      chemotherapy-induced myelosuppression. Our study enhances our understanding of
      BA, identifying roles in metabolic and hemogenic regulation.

PMID- 22958923
TI  - Comparison of an automated algorithm to expert physician interpretation of 80
      lead body surface mapping in the evaluation of acute myocardial ischemia and
      infarction in patients presenting to the emergency department with chest pain:
      results from the Optimal Cardiovascular Diagnostic Evaluation Enabling Faster
      Treatment of Myocardial Infarction trial.
AB  - INTRODUCTION/BACKGROUND: Eighty-lead (80 L) body surface map (BSM) technology
      provides electrocardiogram data for the clinician to interpret. A BSM device also
      offers an automated interpretation. Little information is available about the
      performance of automated algorithm interpretation in comparison to human
      interpretation of the 80 L BSM. METHODS: Interpretations of BSMs by automated
      algorithm and a core laboratory of physician readers from The Optimal
      Cardiovascular Diagnostic Evaluation Enabling Faster Treatment of Myocardial
      Infarction trial were compared. The kappa statistic and its 95% confidence
      interval for concordance were calculated. The effect of BSM quality on
      concordance was also analyzed. RESULTS: 3405 maps for 1601 subjects were reviewed
      by the core laboratory and automated algorithm. There was a combined concordance
      rate of 87.3% (kappa = 0.46; 95% confidence interval, 0.40-0.52). A decrease in
      signal quality was associated with a decrease in concordance between human and
      automated algorithm interpretation (kappa = 0.52 for good quality vs kappa = 0.30
      for poor quality). CONCLUSION: A moderate degree of concordance was noted between
      physician and automated algorithm interpretation of 80 L BSMs. Signal quality of
      80 L electrocardiographic BSM directly affected concordance.

PMID- 22958924
TI  - Distinct and dynamic requirements for mTOR signaling in hematopoiesis and
      leukemogenesis.
AB  - Signaling involving PI3K and AKT regulates cell growth, partly through the mTOR
      kinase complexes 1 and 2. In this issue of Cell Stem Cell, Kalaitzidis et al. and
      Magee et al. reveal unique requirements for mTORC1 and mTORC2 signaling during
      blood development and leukemogenesis induced by loss of PTEN.

PMID- 22958925
TI  - Noisy neurons keep neural stem cells quiet.
AB  - Recently in Nature, Song et al. (2012) show that the neurotransmitter GABA acts
      directly on radial glia-like neural stem cells to maintain quiescence and provide
      a mechanism for how neuronal activity controls the production of new neurons in
      the hippocampus.

PMID- 22958926
TI  - Epithelial stem cells in the esophagus: who needs them?
AB  - In their recent Science publication, Doupe et al. (2012) demonstrate that a
      single population of proliferating progenitor cells is solely responsible for
      homeostatic self-renewal and repair of injured esophageal epithelium. These
      findings argue against an obligate requirement for long-lived (reserve) stem
      cells in adult epithelia.

PMID- 22958927
TI  - Relief with rapamycin: mTOR inhibition protects against radiation-induced
      mucositis.
AB  - In this issue of Cell Stem Cell, Iglesias-Bartolome et al. (2012) show that mTOR
      inhibition with rapamycin protects against mucositis in mice, suggesting
      potential treatment strategies against this harmful side effect of anticancer
      therapies. In normal tissues, rapamycin prevents epithelial stem cell senescence
      by reducing oxidative stress through increased MnSOD.

PMID- 22958928
TI  - Stem cells in the face: tooth regeneration and beyond.
AB  - The face distinguishes one person from another. Postnatal orofacial tissues
      harbor rare cells that exhibit stem cell properties. Despite unmet clinical needs
      for reconstruction of tissues lost in congenital anomalies, infections, trauma,
      or tumor resection, how orofacial stem/progenitor cells contribute to tissue
      development, pathogenesis, and regeneration is largely obscure. This perspective
      article critically analyzes the current status of our understanding of orofacial
      stem/progenitor cells, identifies gaps in our knowledge, and highlights pathways
      for the development of regenerative therapies.

PMID- 22958930
TI  - FLT3-ITD knockin impairs hematopoietic stem cell quiescence/homeostasis, leading
      to myeloproliferative neoplasm.
AB  - Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3
      (FLT3) render the receptor constitutively active driving proliferation and
      survival in leukemic blasts. Expression of FLT3-ITD from the endogenous promoter
      in a murine knockin model results in progenitor expansion and a
      myeloproliferative neoplasm. In this study, we show that this expansion begins
      with overproliferation within a compartment of normally quiescent long-term
      hematopoietic stem cells (LT-HSCs), which become rapidly depleted. This depletion
      is reversible upon treatment with the small molecule inhibitor Sorafenib, which
      also ablates the disease. Although the normal LT-HSC has been defined as FLT3(-)
      by flow cytometric detection, we demonstrate that FLT3 is capable of playing a
      role within this compartment by examining the effects of constitutively activated
      FLT3-ITD. This indicates an important link between stem cell
      quiescence/homeostasis and myeloproliferative disease while also giving novel
      insight into the emergence of FLT3-ITD mutations in the evolution of leukemic
      transformation.

PMID- 22958929
TI  - Less is more: unveiling the functional core of hematopoietic stem cells through
      knockout mice.
AB  - Hematopoietic stem cells (HSCs) represent one of the first recognized somatic
      stem cell types. As such, nearly 200 genes have been examined for roles in HSC
      function in knockout mice. In this review, we compile the majority of these
      reports to provide a broad overview of the functional modules revealed by these
      genetic analyses and highlight some key regulatory pathways involved, including
      cell cycle control, Tgf-beta signaling, Pten/Akt signaling, Wnt signaling, and
      cytokine signaling. Finally, we propose recommendations for characterization of
      HSC function in knockout mice to facilitate cross-study comparisons that would
      generate a more cohesive picture of HSC biology.

PMID- 22958931
TI  - Direct reprogramming of fibroblasts into embryonic Sertoli-like cells by defined
      factors.
AB  - Sertoli cells are considered the "supporting cells" of the testis that play an
      essential role in sex determination during embryogenesis and in spermatogenesis
      during adulthood. Their essential roles in male fertility along with their
      immunosuppressive and neurotrophic properties make them an attractive cell type
      for therapeutic applications. Here we demonstrate the generation of induced
      embryonic Sertoli-like cells (ieSCs) by ectopic expression of five transcription
      factors. We characterize the role of specific transcription factor combinations
      in the transition from fibroblasts to ieSCs and identify key steps in the
      process. Initially, transduced fibroblasts underwent a mesenchymal to epithelial
      transition and then acquired the ability to aggregate, formed tubular-like
      structures, and expressed embryonic Sertoli-specific markers. These Sertoli-like
      cells facilitated neuronal differentiation and self-renewal of neural progenitor
      cells (NPCs), supported the survival of germ cells in culture, and cooperated
      with endogenous embryonic Sertoli and primordial germ cells in the generation of
      testicular cords in the fetal gonad.

PMID- 22958932
TI  - mTOR inhibition prevents epithelial stem cell senescence and protects from
      radiation-induced mucositis.
AB  - The integrity of the epidermis and mucosal epithelia is highly dependent on
      resident self-renewing stem cells, which makes them vulnerable to physical and
      chemical insults compromising the repopulating capacity of the epithelial stem
      cell compartment. This is frequently the case in cancer patients receiving
      radiation or chemotherapy, many of whom develop mucositis, a debilitating
      condition involving painful and deep mucosal ulcerations. Here, we show that
      inhibiting the mammalian target of rapamycin (mTOR) with rapamycin increases the
      clonogenic capacity of primary human oral keratinocytes and their resident self
      renewing cells by preventing stem cell senescence. This protective effect of
      rapamycin is mediated by the increase in expression of mitochondrial superoxide
      dismutase (MnSOD), and the consequent inhibition of ROS formation and oxidative
      stress. mTOR inhibition also protects from the loss of proliferative basal
      epithelial stem cells upon ionizing radiation in vivo, thereby preserving the
      integrity of the oral mucosa and protecting from radiation-induced mucositis.

PMID- 22958933
TI  - Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self
      renewal and leukemia suppression.
AB  - Pten deletion from adult mouse hematopoietic cells activates the PI3-kinase
      pathway, inducing hematopoietic stem cell (HSC) proliferation, HSC depletion, and
      leukemogenesis. Pten is also mutated in human leukemias, but rarely in early
      childhood leukemias. We hypothesized that this reflects developmental changes in
      PI3-kinase pathway regulation. Here we show that Rictor deletion prevents
      leukemogenesis and HSC depletion after Pten deletion in adult mice, implicating
      mTORC2 activation in these processes. However, Rictor deletion had little effect
      on the function of normal HSCs. Moreover, Pten deletion from neonatal HSCs did
      not activate the PI3-kinase pathway or promote HSC proliferation, HSC depletion,
      or leukemogenesis. Pten is therefore required in adult, but not neonatal, HSCs to
      negatively regulate mTORC2 signaling. This demonstrates that some critical tumor
      suppressor mechanisms in adult cells are not required by neonatal cells.
      Developmental changes in key signaling pathways therefore confer temporal changes
      upon stem cell self-renewal and tumor suppressor mechanisms.

PMID- 22958935
TI  - Internet use by Chinese women seeking pregnancy-related information.
AB  - OBJECTIVE: to investigate whether and how Chinese pregnant women used the
      Internet to retrieve pregnancy-related information. DESIGN AND SETTING: a
      descriptive, cross-sectional design using a waiting-room questionnaire was
      employed to obtain information from Chinese pregnant women attending the
      antenatal clinic of a general hospital in Guangzhou, mainland China from
      September to October in 2011. PARTICIPANTS: a total of 335 Chinese women pregnant
      at least 32 weeks participated in the study with the response rate 85%. FINDINGS:
      the great majority of the women (91.9%) had access to the Internet. Most of them
      (88.7%) used it to retrieve health information and began from the beginning of
      the pregnancy. Fetal development and nutrition in pregnancy were the two most
      often mentioned topics of interest. More than half of the women regarded the
      information as reliable. The first most important criterion for judging the
      trustworthiness of web-based information was if the facts were consistent with
      information from other sources; the second most important criterion was if
      references were provided. Most (75.1%) of the women did not discuss the
      information they retrieved from the Internet with their health professionals.
      CONCLUSION: the Internet was a common source for pregnancy related information
      among Chinese pregnant women, the same as that in the western countries. Health
      professionals should be able to guide Chinese pregnant women to high-quality, web
      based information and then take the opportunity to discuss this information with
      them during antenatal visits, consultations and childbirth education classes.

PMID- 22958934
TI  - mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked
      leukemogenesis.
AB  - The mechanistic target of rapamycin (mTOR) pathway serves as a key sensor of
      cellular-energetic state and functions to maintain tissue homeostasis.
      Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC)
      function and is associated with leukemogenesis. However, the roles of the unique
      mTOR complexes (mTORCs) in hematopoiesis and leukemogenesis have not been
      adequately elucidated. We deleted the mTORC1 component, regulatory-associated
      protein of mTOR (Raptor), in mouse HSCs and its loss causes a nonlethal phenotype
      characterized by pancytopenia, splenomegaly, and the accumulation of monocytoid
      cells. Furthermore, Raptor is required for HSC regeneration, and plays largely
      nonredundant roles with rapamycin-insensitive companion of mTOR (Rictor) in these
      processes. Ablation of Raptor also significantly extends survival of mice in
      models of leukemogenesis evoked by Pten deficiency. These data delineate critical
      roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical
      strategies based on chronic mTORC1 inhibition.

PMID- 22958936
TI  - Factors related to under-diagnosis and under-treatment of childhood asthma in
      metropolitan France.
AB  - BACKGROUND: Under-diagnosis and under-treatment of childhood asthma were
      investigated in France using data collected during the 6 Cities Study, the French
      contribution to the International Study of Asthma and Allergies in Childhood.
      METHODS: 7,781 schoolchildren aged between 9 and 10 years underwent a medical
      visit including skin prick tests to common allergens and exercise test for
      Exercise-Induced Asthma (EIA) and their parents filled in a standardized
      questionnaire on asthma, management, treatment and potential risk factors.
      RESULTS: 903 children reported asthma (11.6%), 377 without a doctor's diagnosis.
      Of the 526 participants with a diagnosis of asthma confirmed by a doctor (58.2%),
      353 were treated and 76 were not treated during the year preceding the
      investigation despite their diagnosis. The information on the treatment was
      missing for the rest of individuals diagnosed with asthma (n = 97). Having a
      treatment was significantly associated with severe asthma and with the presence
      of other respiratory and allergic stigmata (atopic eczema, rhinitis, positive
      skin allergy tests, and EIA). In addition, having a treatment did not correspond
      to a good control of the disease. Similarly, children with asthma-like symptoms
      but without doctor-diagnosed asthma had asthma less well controlled than children
      with diagnosed asthma. They were also more exposed to passive smoking and traffic
      but had fewer pets. In contrast, diagnosed children reported more frequently a
      small weight at birth and a preterm birth. CONCLUSIONS: In France, childhood
      asthma is still under-diagnosed and under-treated and environmental factors play
      a role in these phenomena.

PMID- 22958938
TI  - The hook effect in calcitonin immunoradiometric assay: a case report.
AB  - The hook effect, which has long been detected and documented for
      immunoradiometric assays (IRMA) such as those measuring prolactin or
      thyroglobulin, occurs when the serum antigen level is extremely high, thus
      inducing a bias in the methodology of measurement. RESULTS: We report the case of
      an 80-year-old man with confirmed medullary thyroid carcinoma (MTC). In the case
      reported here, the clinical status of the patient contrasts with his tumor
      antigen, serum calcitonin (CT), concentrations. The measured increased CT
      concentrations revealed the presence of a hook effect. This phenomenon occurs due
      to an excess of antigen during the one-step IRMA where the signal antibodies,
      bound to the non-captured antigens, are washed out during the measurement,
      inducing the loss of signal. Aiming to prevent the "hook effect", successive
      dilutions of the same sample of serum were done. CONCLUSIONS: Previous studies
      have shown when one-step IRMA reveals high concentrations of a tumor serum
      antigen (i.e. prolactin or thyroglobulin), a two-step IRMA or a systematic 1:10
      dilution of the serum sample prevents the formation of the "hook effect". In our
      case report, the CT "hook effect" formation was prevented by performing serial
      dilutions of the serum sample.

PMID- 22958939
TI  - Private health insurance in South Korea: an international comparison.
AB  - OBJECTIVES: The goal of this study is to present the historical and policy
      background of the expansion of private health insurance in South Korea in the
      context of the National Health Insurance (NHI) system, and to provide empirical
      evidence on whether the increased role of private health insurance may
      counterbalance government financing, social security contributions, out-of-pocket
      payments, and help stabilize total health care spending. METHODS: Using OECD
      Health Data 2011, we used a fixed effects model estimation. In this model, we
      allow error terms to be serially correlated over time in order to capture the
      association of private health insurance financing with three other components of
      health care financing and total health care spending. RESULTS: The descriptive
      observation of the South Korean health care financing shows that social security
      contributions are relatively limited in South Korea, implying that high out-of
      pocket payments may be alleviated through the enhancement of NHI benefit coverage
      and an increase in social security contributions. Estimation results confirm that
      private health insurance financing is unlikely to reduce government spending on
      health care and social security contributions. We find evidence that out-of
      pocket payments may be offset by private health insurance financing, but to a
      limited degree. Private health insurance financing is found to have a
      statistically significant positive association with total spending on health
      care. This indicates that the duplicated coverage effect on service demand may
      cancel out the potential efficiency gain from market initiatives driven by the
      active involvement of private health insurance. CONCLUSIONS: This study finds
      little evidence for the benefit of private insurance initiatives in coping with
      the fiscal challenges of the South Korean NHI program. Further studies on the
      managerial interplay among public and private insurers and on behavioral
      responses of providers and patients to a given structure of private-public
      financing are warranted to formulate the adequate balance between private health
      insurance and publicly funded universal coverage.

PMID- 22958940
TI  - An examination of variations in the uptake of prostate cancer screening within
      and between the countries of the EU-27.
AB  - OBJECTIVES: Prostate specific antigen (PSA) testing as a part of a prostate
      cancer control strategy is the subject of much debate. This paper examines
      variations in the uptake of PSA testing across Europe and the role of individual
      and contextual variables in explaining this variation. METHODS: Data were taken
      from Eurobarometer 66.2 "Health in the European Union" 2006 on self-reported
      uptake of screening. Data related to men across the EU-27 and Croatia, aged 40
      and over (N=6986). A logistic regression analysis examines the role of individual
      characteristics across and within the countries. RESULTS: A range of individual
      characteristics were found to be statistically significant predictors of uptake
      including education, marital status, and smoking status. Socio-economic status
      (SES) was also a statistically significant predictor of the likelihood of
      screening. Variation across countries in uptake was evident; importantly a
      significant role was accorded primary care in explaining variation in uptake.
      CONCLUSION: Uptake of PSA testing varies considerably within and across European
      countries. Differences within states relate to the characteristics of individuals
      offered tests and differences between states, to the system of primary care in
      operation. Given the significant welfare losses implicit in the evident
      variations the role of primary care warrants further investigation.

PMID- 22958937
TI  - Electrophysiological and contractile function of cardiomyocytes derived from
      human embryonic stem cells.
AB  - Human embryonic stem cells have emerged as the prototypical source from which
      cardiomyocytes can be derived for use in drug discovery and cell therapy.
      However, such applications require that these cardiomyocytes (hESC-CMs)
      faithfully recapitulate the physiology of adult cells, especially in relation to
      their electrophysiological and contractile function. We review what is known
      about the electrophysiology of hESC-CMs in terms of beating rate, action
      potential characteristics, ionic currents, and cellular coupling as well as their
      contractility in terms of calcium cycling and contraction. We also discuss the
      heterogeneity in cellular phenotypes that arises from variability in cardiac
      differentiation, maturation, and culture conditions, and summarize present
      strategies that have been implemented to reduce this heterogeneity. Finally, we
      present original electrophysiological data from optical maps of hESC-CM clusters.

PMID- 22958942
TI  - Ischemic heart disease and women: more answers are needed.

PMID- 22958943
TI  - Cost-effectiveness of dabigatran for stroke prevention in non-valvular atrial
      fibrillation in Spain.
AB  - INTRODUCTION AND OBJECTIVES: Assessment of the cost-effectiveness of dabigatran
      for the prevention of stroke and systemic embolism in patients with non-valvular
      atrial fibrillation in Spain, from the perspective of the National Health System.
      METHODS: Adaptation of a Markov chain model that simulates the natural history of
      the disease over the lifetime of a cohort of 10,000 patients with non-valvular
      atrial fibrillation. Model comparators were warfarin in a first scenario, and a
      real world prescribing pattern in a second scenario, in which 60% of the patients
      were treated with vitamin K antagonists, 30% with acetylsalicylic acid, and 10%
      received no treatment. Deterministic and probabilistic sensitivity analyses were
      performed. RESULTS: Dabigatran reduced the occurrence of clinical events in both
      scenarios, providing gains in quantity and quality of life. The incremental cost
      effectiveness ratio for dabigatran compared to warfarin was 17,581 euros/quality
      adjusted life year gained and 14,118 euros/quality-adjusted life year gained when
      compared to the real world prescribing pattern. Efficiency in subgroups was
      demonstrated. When the social costs were incorporated into the analysis,
      dabigatran was found to be a dominant strategy (ie, more effective and less
      costly). The model proved to be robust. CONCLUSIONS: From the perspective of the
      Spanish National Health System, dabigatran is an efficient strategy for the
      prevention of stroke in patients with non-valvular atrial fibrillation compared
      to warfarin and to the real-world prescribing pattern; incremental cost
      effectiveness ratios were below the 30,000 euros/quality-adjusted life year
      threshold in both scenarios. Dabigatran would also be a dominant strategy from
      the societal perspective, providing society with a more effective therapy at a
      lower cost compared to the other 2 alternatives. Full English text available
      from:www.revespcardiol.org.

PMID- 22958944
TI  - Trends in adult asthma hospitalization: gender-age effect.
AB  - BACKGROUND: Hospital admissions due to asthma are a reliable source of
      information on the morbidity of the disease which, after the increase observed in
      the last quarter of the last century, shows a declining trend in the last few
      years. The aim of this study was to look at hospital admission trends due to
      asthma in our community and analyze some of its associated factors. METHODS:
      Retrospective analysis of all hospital admissions involving adults aged 15 years
      and older with asthma as the primary or secondary diagnosis (if the first
      diagnosis was respiratory failure or respiratory infection) in Public Health
      Service hospitals in the Galician region of Spain between the years 1995-2009
      (total 24,766 admissions). RESULTS: The majority of patients admitted were female
      (71%), over 60 years of age (64%), and admission occurred predominantly in the
      winter months. The hospitalization rate due to asthma tripled over the period
      studied, this being mainly accounted for by women aged over 60 years. Mean
      hospital stay was 9.2 days, longer in older patients or those admitted over the
      weekend. CONCLUSIONS: A significant increase in hospital admissions due to asthma
      over the last few years has been observed in our community, mainly involving
      older women. The mean stay seems long, increasing with patients' age and
      admission over the weekend.

PMID- 22958945
TI  - Factors that predict discharge destination for patients in transitional care: a
      prospective observational cohort study.
AB  - OBJECTIVE: To investigate factors that predict discharge destination for patients
      making the transition from hospital to the community. METHODS: Using a
      prospective cohort design, 696 patients from 11 Transition Care Programs were
      recruited. Baseline patient and program characteristics were considered for
      predicting discharge destination, functional status, and patient length of stay.
      RESULTS: An increased physiotherapy staffing ratio in Transition Care Program was
      associated with an increased likelihood that a patient was discharged home, with
      an improved functional or mobility status, and after a shorter length of stay.
      The other factor that predicted discharge to home included having an Aged Care
      Assessment Service classification of low level care or home with a support
      package. An increased physiotherapy staffing level also reduced the likelihood of
      discharge to low level or high level care. The other factors that predicted
      discharge to low level care were having higher mobility status and older age; the
      other factor associated with increased likelihood of predicting discharge to high
      level care was having an Aged Care Assessment Service classification of high
      level care. CONCLUSIONS: Factors on admission that predicted discharge
      destination were program physiotherapy staffing ratios, Aged Care Assessment
      Service assessment, age and mobility status.

PMID- 22958946
TI  - Early probiotic supplementation for allergy prevention: long-term outcomes.

PMID- 22958947
TI  - Allergic symptoms after pandemic influenza vaccination rarely mediated by vaccine
      specific IgE.

PMID- 22958949
TI  - Comparison of different liquid anaerobic digestion effluents as inocula and
      nitrogen sources for solid-state batch anaerobic digestion of corn stover.
AB  - Effluents from three liquid anaerobic digesters, fed with municipal sewage
      sludge, food waste, or dairy waste, were evaluated as inocula and nitrogen
      sources for solid-state batch anaerobic digestion of corn stover in mesophilic
      reactors. Three feedstock-to-effluent (F/E) ratios (i.e., 2, 4, and 6) were
      tested for each effluent. At an F/E ratio of 2, the reactor inoculated by dairy
      waste effluent achieved the highest methane yield of 238.5L/kg VS(feed), while at
      an F/E ratio of 4, the reactor inoculated by food waste effluent achieved the
      highest methane yield of 199.6L/kg VS(feed). The microbial population and
      chemical composition of the three effluents were substantially different. Food
      waste effluent had the largest population of acetoclastic methanogens, while
      dairy waste effluent had the largest populations of cellulolytic and xylanolytic
      bacteria. Dairy waste also had the highest C/N ratio of 8.5 and the highest
      alkalinity of 19.3g CaCO(3)/kg. The performance of solid-state batch anaerobic
      digestion reactors was closely related to the microbial status in the liquid
      anaerobic digestion effluents.

PMID- 22958948
TI  - Porcine sialoadhesin: a newly identified xenogeneic innate immune receptor.
AB  - Extracorporeal porcine liver perfusion is being developed as a bridge to liver
      allotransplantation for patients with fulminant hepatic failure. This strategy is
      limited by porcine Kupffer cell destruction of human erythrocytes, mediated by
      lectin binding of a sialic acid motif in the absence of antibody and complement.
      Sialoadhesin, a macrophage restricted lectin that binds sialic acid, was
      originally described as a sheep erythrocyte binding receptor. Given similarities
      between sialoadhesin and the unidentified macrophage lectin in our model, we
      hypothesized porcine sialoadhesin contributed to recognition of human
      erythrocytes. Two additional types of macrophages were identified to bind human
      erythrocytes-spleen and alveolar. Expression of sialoadhesin was confirmed by
      immunofluorescence in porcine tissues and by flow cytometry on primary
      macrophages. A stable transgenic cell line expressing porcine sialoadhesin (pSn
      CHO) bound human erythrocytes, while a sialoadhesin mutant cell line did not.
      Porcine macrophage and pSn CHO recognition of human erythrocytes was inhibited
      approximately 90% by an antiporcine sialoadhesin monoclonal antibody and by human
      erythrocyte glycoproteins. Furthermore, this binding was substantially reduced by
      sialidase treatment of erythrocytes. These data support the hypothesis that
      porcine sialoadhesin is a xenogeneic receptor that mediates porcine macrophage
      binding of human erythrocytes in a sialic acid-dependent manner.

PMID- 22958951
TI  - Risk factors for herpes zoster reactivation in maintenance hemodialysis patients.
AB  - OBJECTIVE: Herpes zoster (HZ) reactivation is common in immunocompromised
      patients. Advanced renal failure is also reportedly associated with impairment of
      cellular immunity. There is not any study yet assessing risk factors of HZ
      reactivation in hemodialysis patients. METHODS: All patients undergoing
      maintenance hemodialysis for more than 3 months and who developed HZ between
      2000/01/01 and 2009/12/31 in a tertiary referral medical center were identified,
      and matched 1:1 to hemodialysis patients without HZ by age and gender.
      Multivariate-adjusted conditional logistic regression model was constructed to
      determine possible risk factors. RESULTS: Out of a total of 126 maintenance
      hemodialysis patients (65.3% female), 63 belonged to the HZ reactivation group
      and 63 to the age/sex matched control patients. Conditional logistic regression
      model linked corticosteroid use with heightened risk (odds ratio [OR] 20.2, 95%
      confidence interval [CI] 3.5-125.6; p=0.002), while iron therapy and 1alpha
      hydroxylated vitamin D were associated with significantly lower likelihood of
      developing HZ (OR 0.12, 95%CI 0.0-0.6; p=0.01, and OR 0.06, 95% CI 0.0-0.4;
      p=0.005 respectively). CONCLUSIONS: Use of iron preparations and 1alpha
      hydroxylated vitamin D is potentially associated with less risk of developing HZ
      reactivation in maintenance hemodialysis patients.

PMID- 22958950
TI  - Accumbens functional connectivity during reward mediates sensation-seeking and
      alcohol use in high-risk youth.
AB  - BACKGROUND: Differences in fronto-striatal connectivity in problem substance
      users have suggested reduced influence of cognitive regions on reward-salience
      regions. Youth with a family history of alcoholism (FH+) have disrupted ventral
      striatal processing compared with controls with no familial risk (FH-). As
      sensation-seeking represents an additional vulnerability factor, we hypothesized
      that functional connectivity during reward anticipation would differ by family
      history, and would mediate the relationship between sensation-seeking and
      drinking in high-risk subjects. METHODS: Seventy 18-22 year olds (49 FH+/21 FH-)
      performed a monetary incentive delay task during functional magnetic resonance
      imaging. Group connectivity differences for incentive (reward/loss) vs. neutral
      conditions were evaluated with psychophysiological interaction (PPI) analysis,
      seeded in nucleus accumbens (NAcc). Indirect effects of sensation-seeking on
      drinking volume through accumbens connectivity were tested. RESULTS: NAcc
      connectivity with paracentral lobule/precuneus and sensorimotor areas was
      decreased for FH- vs. increased for FH+ during incentive anticipation. In FH+,
      task-related functional coupling between left NAcc and supplementary sensorimotor
      area (SSMA) and right precuneus correlated positively with sensation-seeking and
      drinking volume and mediated their relationship. In FH-, left NAcc-SSMA
      connectivity correlated negatively with sensation-seeking but was not related to
      drinking. CONCLUSIONS: These results suggest preexisting differences in accumbens
      reward-related functional connectivity in high-risk subjects. NAcc coupling with
      SSMA, involved in attention and motor networks, and precuneus, a default mode
      structure, appear to mediate sensation-seeking's effect on drinking in those most
      at-risk. Differences in accumbens connectivity with attention/motor/default
      networks, rather than control systems, may influence the reward system's role in
      vulnerability for substance abuse.

PMID- 22958952
TI  - Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20
      in lung macrophages.
AB  - BACKGROUND: Alcohol abuse is involved in the pathogenesis of multiple organ
      disorders; the underlying mechanism is incompletely understood. The ubiquitin
      editing enzyme A20 is involved in regulating activities in the cell. Suppression
      of A20 is suggested as one factor in the initiation of inflammation. This study
      investigates the mechanism by which chronic alcohol consumption modulates the
      levels of ubiquitin editing enzyme A20 in macrophages and further contributes to
      induce endothelial barrier dysfunction in the lung. METHODS: Mice were gavage-fed
      with 40% alcohol daily for 0-3 weeks. Airway macrophages were collected by lung
      lavage. Expression of ubiquitin editing enzyme A20 in isolated macrophages was
      assessed at both mRNA and protein levels. The endothelial barrier function of the
      lung was evaluated by the Evans blue method. RESULTS: Mice treated with alcohol
      for 3 weeks showed an increase in cell infiltration in the lung in response to
      exposure to peptidoglycan; over 80% of the infiltrated cells were macrophages.
      Furthermore, we observed that A20 level was suppressed in macrophages of mice
      treated with alcohol; the levels of tumor necrosis factor, interleukin-6 and
      nuclear factor kappa B in macrophage were increased. In addition, the endothelial
      barrier function of the lung was compromised, showing excessive infiltration of
      Evans blue in the lung indicating lung edema. Pretreatment with synthesized A20
      inhibited alcohol-induced lung endothelial barrier dysfunction. CONCLUSIONS: We
      conclude that chronic alcohol ingestion disturbs the endothelial barrier function
      in the lung by modulating macrophage properties. Increase in A20 in the cell may
      have potential for the treatment of inflammatory disorders.

PMID- 22958953
TI  - Body composition and survival in stable coronary heart disease: impact of lean
      mass index and body fat in the "obesity paradox".
AB  - OBJECTIVES: Our goal was to determine the impact of lean mass index (LMI) and
      body fat (BF) on survival in patients with coronary heart disease (CHD).
      BACKGROUND: An inverse relationship between obesity and prognosis has been
      demonstrated (the "obesity paradox") in CHD, which has been explained by
      limitations in the use of body mass index in defining body composition. METHODS:
      We studied 570 consecutive patients with CHD who were referred to cardiac
      rehabilitation, stratified as Low (<=25% in men and <=35% in women) and High
      (>25% in men and >35% in women) BF and as Low (<=18.9 kg/m2 in men and <=15.4
      kg/m2 in women) and High LMI, and followed for 3 years for survival. RESULTS:
      Mortality is inversely related to LMI (p<0.0001). Mortality was highest in the
      Low BF/Low LMI group (15%), which was significantly higher than in the other 3
      groups, and lowest in the High BF/High LMI group (2.2%), which was significantly
      lower than in the other 3 groups. In Cox regression analysis as categoric
      variables, low LMI (hazard ratio [HR]: 3.1; 95% confidence interval [CI]: 1.3 to
      7.1) and low BF (HR: 2.6; 95% CI: 1.1 to 6.4) predicted higher mortality, and as
      continuous variables, high BF (HR: 0.91; 95% CI: 0.85 to 0.97) and high LMI (HR:
      0.81; 95% CI: 0.65 to 1.00) predicted lower mortality. CONCLUSIONS: In patients
      with stable CHD, both LMI and BF predict mortality, with mortality particularly
      high in those with Low LMI/Low BF and lowest in those with High LMI/High BF.
      Determination of optimal body composition in primary and secondary CHD prevention
      is needed.

PMID- 22958954
TI  - Are racial/ethnic gaps in the use of cardiac resynchronization therapy
      narrowing?: an analysis of 107,096 patients from the National Cardiovascular Data
      Registry's ICD Registry.

PMID- 22958955
TI  - Catheter ablation for the treatment of atrial fibrillation: have we been
      targeting the wrong organ?

PMID- 22958956
TI  - Contemporary results for proximal aortic replacement in North America.
AB  - OBJECTIVES: The purpose of this study was to characterize operative outcomes for
      ascending aorta and arch replacement on a national scale and to develop risk
      models for mortality and major morbidity. BACKGROUND: Contemporary outcomes for
      ascending aorta and arch replacement in North America are unknown. METHODS: We
      queried the Society of Thoracic Surgeons Database for patients undergoing
      ascending aorta (with or without root) with or without arch replacement from 2004
      to 2009. The database captured 45,894 cases, including 12,702 root, 22,048
      supracoronary ascending alone, 6,786 ascending plus arch, and 4,358 root plus
      arch. Baseline characteristics and clinical outcomes were analyzed. A
      parsimonious multivariable logistic regression model was constructed to predict
      risks of mortality and major morbidity. RESULTS: Operative mortality was 3.4% for
      elective cases and 15.4% for nonelective cases. A risk model for operative
      mortality (c-index 0.81) revealed a risk-adjusted odds ratio for death after
      emergent versus elective operation of 5.9 (95% confidence interval: 5.3 to 6.6).
      Among elective patients, end-stage renal disease and reoperative status were the
      strongest predictors of mortality (adjusted odds ratios: 4.0 [95% confidence
      interval: 2.6 to 6.4] and 2.3 (95% confidence interval: 1.9 to 2.7],
      respectively; p < 0.0001). CONCLUSIONS: Current outcomes for ascending aorta and
      arch replacement in North America are excellent for elective repair; however,
      results deteriorate for nonelective status, suggesting that increased screening
      and/or lowering thresholds for elective intervention could potentially improve
      outcomes. The predictive models presented may serve clinicians in counseling
      patients.

PMID- 22958957
TI  - 2-year patient-related versus stent-related outcomes: the SORT OUT IV
      (Scandinavian Organization for Randomized Trials With Clinical Outcome IV) Trial.
AB  - OBJECTIVES: There are limited head-to-head randomized data on patient-related
      versus stent-related outcomes for everolimus-eluting stents (EES) and sirolimus
      eluting stents (SES). BACKGROUND: In the SORT OUT IV (Scandinavian Organization
      for Randomized Trials With Clinical Outcome IV) trial, comparing the EES with the
      SES in patients with coronary artery disease, the EES was noninferior to the SES
      at 9 months. METHODS: The primary endpoint was a composite: cardiac death,
      myocardial infarction (MI), definite stent thrombosis, or target vessel
      revascularization. Safety and efficacy outcomes at 2 years were further assessed
      with specific focus on patient-related composite (all death, all MI, or any
      revascularization) and stent-related composite outcomes (cardiac death, target
      vessel MI, or symptom-driven target lesion revascularization). A total of 1,390
      patients were assigned to receive the EES, and 1,384 patients were assigned to
      receive the SES. RESULTS: At 2 years, the composite primary endpoint occurred in
      8.3% in the EES group and in 8.7% in the SES group (hazard ratio [HR]: 0.94, 95%
      confidence interval [CI]: 0.73 to 1.22). The patient-related outcome: 15.0% in
      the EES group versus 15.6% in the SES group, (HR: 0.95, 95% CI: 0.78 to 1.15),
      and the stent-related outcome: 5.2% in the EES group versus 5.3% in the SES group
      (HR: 0.97, 95% CI: 0.70 to 1.35) did not differ between groups. Rate of definite
      stent thrombosis was lower in the EES group (0.2% vs. 0.9%, (HR: 0.23, 95% CI:
      0.07 to 0.80). CONCLUSIONS: At 2-year follow-up, the EES was found to be
      noninferior to the SES with regard to both patient-related and stent-related
      clinical outcomes.

PMID- 22958958
TI  - A randomized comparison of pulmonary vein isolation with versus without
      concomitant renal artery denervation in patients with refractory symptomatic
      atrial fibrillation and resistant hypertension.
AB  - OBJECTIVES: The aim of this prospective randomized study was to assess the impact
      of renal artery denervation in patients with a history of refractory atrial
      fibrillation (AF) and drug-resistant hypertension who were referred for pulmonary
      vein isolation (PVI). BACKGROUND: Hypertension is the most common cardiovascular
      condition responsible for the development and maintenance of AF. Treating drug
      resistant hypertension with renal denervation has been reported to control blood
      pressure, but any effect on AF is unknown. METHODS: Patients with a history of
      symptomatic paroxysmal or persistent AF refractory to >=2 antiarrhythmic drugs
      and drug-resistant hypertension (systolic blood pressure >160 mm Hg despite
      triple drug therapy) were eligible for enrolment. Consenting patients were
      randomized to PVI only or PVI with renal artery denervation. All patients were
      followed >=1 year to assess maintenance of sinus rhythm and to monitor changes in
      blood pressure. RESULTS: Twenty-seven patients were enrolled, and 14 were
      randomized to PVI only, and 13 were randomized to PVI with renal artery
      denervation. At the end of the follow-up, significant reductions in systolic
      (from 181 +/- 7 to 156 +/- 5, p < 0.001) and diastolic blood pressure (from 97 +/
      6 to 87 +/- 4, p < 0.001) were observed in patients treated with PVI with renal
      denervation without significant change in the PVI only group. Nine of the 13
      patients (69%) treated with PVI with renal denervation were AF-free at the 12
      month post-ablation follow-up examination versus 4 (29%) of the 14 patients in
      the PVI-only group (p = 0.033). CONCLUSIONS: Renal artery denervation reduces
      systolic and diastolic blood pressure in patients with drug-resistant
      hypertension and reduces AF recurrences when combined with PVI.

PMID- 22958959
TI  - Transvenous mitral valve replacement after failure of surgical ring annuloplasty.

PMID- 22958961
TI  - Aspiration of tracheoesophageal prosthesis in a laryngectomized patient.
AB  - BACKGROUND: The voice prosthesis inserted into a tracheoesophageal fistula has
      become the most widely used device for voice rehabilitation in patients with
      total laryngectomy. CASE PRESENTATION: We describe a case of tracheoesophageal
      prosthesis' (TEP) aspiration in a laryngectomized patient, with permanent
      tracheal stoma, that appeared during standard cleaning procedure, despite a
      programme of training for the safe management of patients with voice prosthesis.
      CONCLUSIONS: The definitive diagnosis and treatment were performed by flexible
      bronchoscopy, that may be considered the procedure of choice in these cases, also
      on the basis of the literature.

PMID- 22958962
TI  - Differences in talker recognition by preschoolers and adults.
AB  - Talker variability in speech influences language processing from infancy through
      adulthood and is inextricably embedded in the very cues that identify speech
      sounds. Yet little is known about developmental changes in the processing of
      talker information. On one account, children have not yet learned to separate
      speech sound variability from talker-varying cues in speech, making them more
      sensitive than adults to talker variation. A different account is that children
      are less developed than adults at recognizing speech sounds and at recognizing
      talkers, and development involves protracted tuning of both recognition systems.
      The current research presented preschoolers and adults (N=180) with voices linked
      to two distinct cartoon characters. After exposure, participants heard each
      talker and selected which character was speaking. Consistent with the protracted
      tuning hypothesis, children were much less accurate than adults when talkers were
      matched on age, gender, and dialect (Experiments 1-3), even when prosody differed
      (Experiment 5). Children were highly accurate when voices differed in gender
      (Experiment 2) or age (mother vs. daughter; Experiment 6), suggesting that
      greater acoustic dissimilarity facilitated encoding. Implications for speech
      sound processing are discussed, as are the roles of language knowledge and the
      nature of talker perceptual space in talker encoding.

PMID- 22958963
TI  - On the threshold of a new era of worldwide exchange.

PMID- 22958960
TI  - Third universal definition of myocardial infarction.

PMID- 22958964
TI  - The editorial process.

PMID- 22958965
TI  - The influence of coracoacromial arch anatomy on rotator cuff tears.
AB  - We performed an anatomic study of 140 cadaver shoulders to correlate the
      influence of the coracoacromial arch anatomy on full-thickness rotator cuff tears
      (RCTs). The presence, location, and size of RCTs were initially documented. After
      dissection was complete 14 dimensional parameters, including humeral head size,
      glenoid size, and location of bony landmarks, were obtained by direct
      measurement. These data were entered into a computerized data base and 24
      additional parameters (lengths, angles, areas) were calculated. The data were
      then subjected to analysis of variance and paired and unpaired t tests to
      determine correlation between the multiple parameters, age, sex, and left-to
      right variance with RCTs. Three-dimensional computer modeling was then used to
      investigate the role of humeral head position in defining the available space
      within the coracoacromial arch (supraspinatus outlet). Overall 20% of the cadaver
      group exhibited full-thickness RCTs. The age group 60 years and older had a 29%
      incidence of RCTs compared with 5% in the group less than 60 years of age. The
      RCT group had a significantly greater anterior projection of the acromion than
      had the intact group (difference = 3.8 mm, p < 0.007). Acromial tilt was 28.5
      degrees  in the RCT group and 33.5 degrees  in the intact group (p < 0.007). The
      supraspinatus outlet area was calculated by determining the total coracoacromial
      arch area and subtracting the area of the humeral head within the coracoacromial
      arch. The supraspinatus outlet was 22.5% smaller in the RCT group (p < 0.07). By
      using a series of measured and calculated parameters, we were able to
      characterize the anatomy of the coracoacromial arch and its relationship with the
      humeral head and to correlate variations in structure with the presence of RCTs.
      These findings may aid in our understanding of outlet impingement as a factor in
      the cause of RCTs.

PMID- 22958966
TI  - An electromyographic analysis of the upper extremity in pitching.
AB  - The upper extremity is vulnerable to injury during the baseball pitch because of
      the repetitious nature of the action, the extremes in range of motion, and the
      high angular velocities and torques generated at the shoulder and elbow. Hence
      this study was designed to describe the muscle-firing patterns through fine-wire
      electromyography in 29 muscle bellies in the upper extremities of skilled
      pitchers during the fastball pitch. The results demonstrated that the muscles
      functioned with precise timing for joint stabilization to prevent injury, joint
      activation to transfer forces to the ball, and joint deceleration to dissipate
      forces after ball release. The synchrony of reciprocal and sequential muscle
      contraction necessary to accomplish these functions was clearly evident. This
      study provides a better understanding of the coordinated sequence of muscle
      activity during the throwing motion; this understanding is crucial to the
      development of exercise protocols and surgical procedures used for treatment and
      prevention of shoulder and elbow injuries in the throwing athlete.

PMID- 22958967
TI  - Avulsion fracture of the supraglenoid tubercle: A variation of the SLAP lesion.
AB  - Tears of the anterior and posterior/superior labrum (SLAP) are often associated
      with overhead throwing sports. This lesion may be present in the absence of
      glenohumeral instability. Fracture of the supraglenoid tubercle associated with a
      SLAP lesion has not been previously reported. Two cases of supraglenoid tubercle
      fracture associated with the SLAP lesion in overhead throwing activities are
      presented. The presence of a supraglenoid fracture on a plain radiograph is
      uncommon, but such a finding may allow early noninvasive diagnosis of the SLAP
      lesion.

PMID- 22958968
TI  - Surgical anatomy of the axillary nerve.
AB  - Any surgical approach that splits the deltoid puts the axillary nerve at risk
      secondary to extension from traction or sharp dissection. Standard texts an
      anatomy and chapters on surgical approaches frequently state the axillary nerve
      comes to lie approximately 2 inches from the acromion. However, a large series of
      cadavers of varying sex and size on which these measurements had been obtained
      could not be found in an extensive literature search. Fifty-one embalmed
      cadaveric specimens representing 102 shoulders were dissected in the static
      portion of this study. In nearly 20% of cadavers the nerve at some point along
      its course around the humerus in the deltoid muscle was less than 5 cm from the
      palpable edge of the acromion. This was especially true of female cadavers with
      short arm spans; in one cadaver the nerve was 3.1 cm from the acromial edge.
      Abducting the shoulder to 9cr decreases the distance from the nerve to the
      palpable edge of the acromion nearly 30%. Five centimeters does not describe an
      absolute safe zone for the axillary nerve. Furthermore, abduction of the arm
      brings the nerve even closer to commonly used bony landmarks.

PMID- 22958969
TI  - The management of complex distal humerus nonunion in the elderly by elbow
      capsulectomy, triple plating, and ulnar nerve neurolysis.
AB  - Six elderly patients (average age, 68 years) were treated for a complex, low
      supracondylar nonunion of the humerus. Each nonunion had in common an associated
      ulnar neuropathy, extensive periarticular fibrosis, a low synovial nonunion, and
      osteopenic bone. The surgical approach included ulnar nerve neurolysis, complete
      elbow capsulectomy, three strategically placed plates, and autogenous iliac crest
      bone graft. All the nonunions healed and all six patients regained ulnar nerve
      function. The average arc of elbow motion was 102 degrees , with an average
      flexion of 122 degrees  and a flexion contracture of 19 degrees . Radiographic
      follow-up revealed only one case with a focal area of avascular necrosis
      involving a previously ununited intraarticular fracture of the trochlea.

PMID- 22958970
TI  - Reoperation for failed surgical treatment of refractory lateral epicondylitis.
AB  - The reliability of surgical procedures for lateral epicondylitis makes the need
      for reoperation uncommon. In a review of surgical procedures followed by
      reoperation, failures were classified according to first operations followed by
      symptoms similar to those experienced preoperatively (group 1) and first
      operations followed by a different symptom complex (group 2). In group 1 the
      cause of surgical failure was inadequate release or incorrect initial diagnosis,
      most often relating to entrapment of the posterior interosseous nerve. In group 2
      the causes of failure were shown to be capsular or ligamentous insufficiency. A
      careful work-up directed at the above classification and surgical procedures
      specifically directed at the defined cause of previous failure have resulted in
      successful reoperation in 11 (85 %) of 73 patients.

PMID- 22958971
TI  - The treatment of localized metastases in the proximal humerus from renal cell
      carcinoma.
AB  - Four cases of a localized metastatic renal cell carcinoma within the proximal
      humerus are reviewed. In three of these cases radiation therapy resulted in
      relief of bone pain but did not control progression of the secondary tumor. In
      one case palliative radiation treatment combined with intramedullary nailing
      resulted in the total destruction of the whole humerus by secondary tumor during
      the 10-month period before the patient died. In the other three cases aggressive
      surgical treatment was performed. This treatment consisted of an en bloc
      resection of the proximal humerus, with reconstruction of the proximal humerus
      with a long-stem Neer humeral head replacement prosthesis. To obtain a good
      functional result, the soft tissues were reconstructed onto on intercalary
      allograft in one case; artificial rotator cuffs were used in two cases. After a
      mean follow-up period of 20 months, all three patients who underwent aggressive
      treatment hod painless shoulders, with fair function and no recurrence of
      carcinoma. En bloc resection with reconstruction of the proximal humerus is on
      effective method of avoiding limb oblation and contrailing painful solitary
      lesions from metastatic renal cell carcinoma.

PMID- 22958972
TI  - Presidential address: american shoulder and elbow surgeons, tenth anniversary
      annual meeting Seattle, washington, september 4-7, 1991.

PMID- 22958973
TI  - The BTBR T+ tf/J mouse model for autism spectrum disorders-in search of
      biomarkers.
AB  - Autism spectrum disorders (ASD) form a common group of neurodevelopmental
      disorders appearing to be under polygenic control, but also strongly influenced
      by multiple environmental factors. The brain mechanisms responsible for ASD are
      not understood and animal models paralleling related emotional and cognitive
      impairments may prove helpful in unraveling them. BTBR T+ tf/J (BTBR) mice
      display behaviors consistent with the three diagnostic categories for ASD. They
      show impaired social interaction and communication as well as increased
      repetitive behaviors. This review covers much of the data available to date on
      BTBR behavior, neuroanatomy and physiology in search for candidate biomarkers,
      which could both serve as diagnostic tools and help to design effective
      treatments for the behavioral symptoms of ASD.

PMID- 22958976
TI  - Integration of patient safety systems in a suburban hospital.
AB  - Public awareness of hospital misadventure is now common. In response, we describe
      our integrated hospital safety system, which is dependent on the linkage of
      multiple individual safety committees, and the presence on each committee of
      senior and junior multidisciplinary healthcare professionals to provide feedback
      to their peer groups on required improvements.

PMID- 22958975
TI  - Auditory system involvement in late onset Pompe disease: a study of 20 Italian
      patients.
AB  - Glycogen storage disease type II (GSD II), also known as Pompe disease, is an
      autosomal recessive inherited disorder caused by a reduced activity of acid alpha
      glucosidase (GAA). Two different clinical entities have been described: rapidly
      fatal infantile and late onset forms. Hearing loss has been described in classic
      infantile Pompe patients but rarely in late onset cases. The main purpose of this
      study was to investigate the involvement of the auditory system in a cohort of
      Italian patients with late onset GSD II. We have enrolled 20 patients, 12 males
      and 8 females. The auditory system assessment included speech and pure tone
      audiometry, impedance audiometry and auditory brainstem responses (ABR). A
      combined interpretation of those tests allowed us to define the origin of the
      hearing impairment (sensorineural, conductive or mixed). Clinically, all patients
      but one denied subjective hearing disturbances. On the other hand, audiological
      evaluation revealed that 21/40 patient ears (52.5%) had a hearing impairment: 57%
      had a sensorineural deficit, 33% showed a conductive hearing loss whereas 10%
      presented with a mixed pattern. Our study revealed that, in this group of GSDII
      late onset patients, the auditory system impairment was more frequently present
      than thought with a prominent cochlear involvement. Our results emphasize the
      importance of a routinely auditory function evaluation in all forms of Pompe
      disease.

PMID- 22958974
TI  - Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle
      disorders.
AB  - We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or
      HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in
      patients with urea cycle disorders (UCD). STUDY DESIGN: These analyses are based
      on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD
      patients (ages 6-17) who participated in three clinical studies comparing ammonia
      control and pharmacokinetics during steady state treatment with glycerol
      phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid
      equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross
      over fashion and underwent 24-hour blood samples and urine sampling for
      phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. RESULTS:
      Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate
      ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to
      31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation
      indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for
      phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent
      recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0
      for pediatric patients and 68.7 and 71.4 for adult patients on glycerol
      phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose
      was strongest for urinary phenylacetylglutamine excretion, either as morning spot
      urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001),
      followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid
      AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels
      in adult and pediatric patients did not show a consistent relationship with
      either urinary phenylacetylglutamine or ammonia control. CONCLUSION: The findings
      are collectively consistent with substantial yet variable pre-systemic (1st pass)
      conversion of phenylbutyric acid to phenylacetic acid and/or
      phenylacetylglutamine. The variability of blood metabolite levels during the day,
      their weaker correlation with dose, the need for multiple blood samples to
      capture trough and peak, and the inconsistency between phenylacetic acid and
      urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the
      utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary
      phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate
      strongly with dose and appear to be clinically useful non-invasive biomarkers for
      compliance and therapeutic monitoring.

PMID- 22958977
TI  - Structural and photocatalytic studies of Mn doped TiO2 nanoparticles.
AB  - Mn-doped TiO(2) nanoparticles (Ti(1-)(x)Mn(x)O(2); where x=0.00-0.10) were
      synthesized by sol-gel method. The synthesized products were characterized by X
      ray diffraction (XRD), scanning electron microscope (SEM), transmission electron
      microscope (TEM) and UV-Vis spectrometer. The SEM and TEM micrographs revealed
      the agglomerated spherical-like morphology and measurements show that the size of
      crystallites is in the range of 10-20 nm. Optical measurements indicated a red
      shift in the absorption band edge after Mn doping. Direct allowed band gap of
      undoped and Mn-doped TiO(2) nanoparticles measured by UV-Vis spectrometer were
      3.00 and 2.95 eV at 300  degrees C, respectively. Photocatalytic activities of
      TiO(2) and Mn doped TiO(2) were evaluated by irradiating the sample solution of
      methylene blue (MB) dye under ultraviolet and visible light exposure. It was
      found that Mn-doped TiO(2) bleaches MB much faster than undoped TiO(2) upon its
      exposure to the visible light as comparison to ultraviolet light. The experiment
      demonstrated that the photodegradation efficiency of Mn-doped TiO(2) was
      significantly higher than that of undoped TiO(2) upon its exposure to visible
      light.

PMID- 22958978
TI  - FT-IR, FT-Raman spectra, NBO, HOMO-LUMO and thermodynamic functions of 4-chloro-3
      nitrobenzaldehyde based on ab initio HF and DFT calculations.
AB  - FT-IR (4000-400 cm(-1)) and FT-Raman (3500-100 cm(-1)) spectral measurements of 4
      chloro-3-nitrobenzaldehyde have been done. Ab initio (HF/6-311+G(d,p)) and DFT
      (B3LYP/6-311+G(d,p)) calculations have been performed giving energies, optimized
      structures, harmonic vibrational frequencies, infrared intensities and Raman
      activities. A detailed interpretation of the FT-IR and FT-Raman spectra of 4
      chloro-3-nitrobenzaldehyde are reported on the basis of the calculated potential
      energy distribution. Stability of the molecule arising from hyper conjugative
      interactions, charge delocalization has been analyzed using natural bond orbital
      (NBO) analysis. The HOMO and LUMO energy gap reveals that the energy gap reflects
      the chemical activity of the molecule. The thermodynamic functions of the title
      compound have been performed by HF/6-311+G(d,p) and B3LYP/6-311+G(d,p). The
      observed and calculated wave numbers are found to be in good agreement. The
      experimental spectra also coincide satisfactorily with those of theoretically
      constructed spectra. Thermodynamic functions were calculated using vibrational
      wave numbers for different temperatures.

PMID- 22958979
TI  - Synthesis and properties of new luminescent hole transporting materials
      containing triphenylamine and carbazole units.
AB  - Two new blue luminescent hole transporting materials (HTM) containing
      triphenylamine, carbazole units and olefinic linkers (TM1 and TM2) were
      synthesized via Wittig reaction and characterized by (1)H NMR, FT-IR, and HRMS.
      The compounds show good solubility in common organic solvents such as
      dichloromethane, chloroform, tetrahydrofuran and dimethyl formamide. Their
      optical, electrochemical and crystalline properties were investigated by using UV
      Vis, photoluminescence (PL) spectra, cyclic voltammetry (CV) and differential
      scanning calorimetry (DSC), respectively. Quantum-chemical calculation was
      performed to obtain their optimized structures and the electron distribution of
      the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular
      orbital (LUMO) energy levels. The UV-Vis absorption and PL spectra of the two
      compounds in solid state were found to be similar to that when they were in
      dilute THF, which suggests that these compounds remain as an amorphous state in
      solid films. CV measurements show that the two compounds embody suitable HOMO
      levels (in a range of -5.28 to -5.23 eV) for hole injection, which is consistent
      with the calculation consequence. Two compounds possess high glass-transition
      temperature (T(g)) at 96.61 and 90.74  degrees C for TM1 and TM2, respectively,
      suggesting the two compounds could form stable amorphous glassy states. The
      experimental results show that the synthesized compounds have great potential for
      application in organic light-emitting devices (OLEDs).

PMID- 22958980
TI  - Quantum chemical and experimental studies on polymorphism of antiviral drug
      Lamivudine.
AB  - Lamivudine, is chemically known as [4-amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3
      oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one], is an anti-HIV agent belonging to
      the class of the non-nucleoside inhibitors of the HIV-1 virus reverse
      transcriptase. Spectral characteristics of Lamivudine have been studied by
      methods of FTIR, NMR and quantum chemistry. The FTIR and spectra of Lamivudine
      was recorded in the regions 4000-400 cm(-1). The thermal stability of Lamivudine
      was studied by the thermogravimetric analysis (TGA). The isotropic (13)C-nuclear
      magnetic shielding constants of this compound were calculated by employing the
      direct implementation of the gauge including-atomic-orbital (GIAO) method at the
      HF and B3LYP density functional theory using 6-31G(d,p) basis set. The optimized
      molecular geometry, bond orders, harmonic vibrational spectrum of anhydrous and
      hydrated Lamivudine were calculated by restricted Hartree Fock and density
      functional B3LYP method with the 6-31G(d,p) basis set using Gaussian 03W program.

PMID- 22958981
TI  - Polycationic peptide guided spherical ordered self-assembly of biomacromolecules.
AB  - Achieving effective controllable delivery of therapeutic biomacromolecules for
      long action without new molecular entities generation or carriers employed offers
      a promising alternative and significant clinical benefit. We show here that
      recombinant human interferon-alpha (rhIFN) can form a three dimensional ordered
      structure that is featured by spherical semi-crystalline through molecular self
      assembly directed by a polycationic short peptide. The phase diagrams for self
      assembly were constructed to identify the optimal regions for nucleation and
      ordered growth, and which were followed by the physico-chemical characterization
      of the ordered self-assemblies, including morphology, particle size, X-ray
      diffraction, circular dichroism and biological potency evaluations. With varied
      molar ratio of the two composed biomacromolecules, the dissolution behaviors of
      the self-assemblies could be manipulated in vitro and in vivo. The plasma
      pharmacokinetics suggested that s.c. administration of self-assemblies at the
      specified relative proportion of rhIFN to polycationic peptide offered a
      significant prolonged duration time of rhIFN blood levels up to seven days.
      Moreover, molecular simulation was performed to better understand their binding
      site and mode. The work described here demonstrates the possibility of spherical
      ordered self-assembly of biomacromolecules for controllable delivery application
      of therapeutic proteins.

PMID- 22958982
TI  - Prevalence of smoking and chronic obstructive pulmonary disease amongst teachers
      working in Kocaeli, Turkey.
AB  - AIM: To evaluate smoking and COPD prevalence amongst teachers working in the
      schools of Kocaeli City, Turkey. METHOD: In this cross-sectional study, a
      questionnaire focusing on respiratory symptoms and smoking habits was
      administered to all participants who accepted to join the study.All subjects also
      underwent a physical examination and a pulmonary function test performed with
      portable spirometer. According to GOLD criteria, subjects who had post
      bronchodilator FEV1/FVC < 70% and negative reversibility test were classified as
      COPD. RESULTS: A total of 685 teachers were included [female n = 307 (45%), male
      n = 378 (55%)] with mean age 38.9 +/- 8.9 years. Smoking habit was evaluated in
      660 subjects: 291 (44.1%) were smokers, 252 (38.2%) were non-smokers and 117
      (17.7%) were ex-smokers. Pulmonary function test was available in 651 subjects
      and 510 (78.3%) were defined as normal on spirometric analysis. Small airway
      obstruction was found in 115 of the cases (17.7%) in whom FEF25-75 level was
      found to be lower than 70% predicted. FEV1/FVC level was lower than 70% in 16
      subjects (2.5%). Five subjects who had positive reversibility test were excluded
      from the study. The remaining 11 subjects who were considered as COPD consisted
      of 2 (18%) females and 9 (82%) males. Six of these subjects were aged over 40
      years. CONCLUSION: Spirometry has an important role in early diagnosis of COPD.
      Spirometric evaluation of cases with risk factors for COPD could be helpful in
      diagnosing patients before the progressive decline in lung function begins.
      Further studies are needed to evaluate whether the interventional strategies at
      this stage such as smoking cessation could prevent the progression of disease.

PMID- 22958984
TI  - Improving outcomes in umbilical cord blood transplantation: state of the art.
AB  - Only 30% of patients who require an allogeneic hematopoietic cell transplant will
      have a HLA matched sibling donor. Many patients, particularly those patients with
      diverse racial and ethnic backgrounds, may not be able to identify a suitably
      matched unrelated donor. Over 25,000 umbilical cord blood transplant procedures
      have been performed in the last 25years. Considerable challenges exist in
      defining the appropriate conditioning regimen and graft vs host disease
      prophylaxis, surmounting issues of cell dose and delayed engraftment, and
      improving immune recovery. In this review, we discuss strategies to improve
      umbilical cord blood transplant outcomes, focusing on cord blood unit selection,
      expansion, and homing efficiency.

PMID- 22958983
TI  - Measures of body habitus are associated with lung function in adults with cystic
      fibrosis: a population-based study.
AB  - BACKGROUND: Body habitus differences may explain some of the variation in lung
      function between individuals with cystic fibrosis (CF). We tested the hypothesis
      that measures of lean muscle mass and obesity are independently associated with
      lung function in CF. METHODS: Cross-sectional study design using UK CF registry
      data from 2096 clinically stable adults. RESULTS: Serum creatinine and BMI were
      positively and independently associated with FEV1 and FVC. One standard deviation
      increment in serum creatinine was associated with an FEV1 increase of 171ml (95%
      confidence intervals CI: +116 to +227ml) in males and 90ml (95% CI: +46 to
      +133ml) in females. Compared to the reference group of 20-24.9kg/m(2), those with
      a BMI<20kg/m(2) had lower FEV1 with values of -642ml (95%CI: -784 to -500ml) for
      males and -468ml (95%CI: -564 to -372ml) for females. CONCLUSIONS: Prospective
      studies and controlled trials are required to ascertain if these associations
      have therapeutic potential in modifying disease progression.

PMID- 22958985
TI  - Automatic segmentation of human facial tissue by MRI-CT fusion: a feasibility
      study.
AB  - The aim of this study was to develop automatic image segmentation methods to
      segment human facial tissue which contains very thin anatomic structures. The
      segmentation output can be used to construct a more realistic human face model
      for a variety of purposes like surgery planning, patient specific prosthesis
      design and facial expression simulation. Segmentation methods developed were
      based on Bayesian and Level Set frameworks, which were applied on three image
      types: magnetic resonance imaging (MRI), computerized tomography (CT) and fusion,
      in which case information from both modalities were utilized maximally for every
      tissue type. The results on human data indicated that fusion, thickness adaptive
      and postprocessing options provided the best muscle/fat segmentation scores in
      both Level Set and Bayesian methods. When the best Level Set and Bayesian methods
      were compared, scores of the latter were better. Number of algorithm parameters
      (to be trained) and computer run time measured were also in favour of the
      Bayesian method.

PMID- 22958986
TI  - Assessing automated extraction of prognostic information for intensive care unit
      patients.

PMID- 22958987
TI  - Murder and euthanasia accusations against physicians.

PMID- 22958988
TI  - Derivation and validation of automated electronic search strategies to extract
      Charlson comorbidities from electronic medical records.
AB  - OBJECTIVE: To develop and validate automated electronic note search strategies
      (automated digital algorithm) to identify Charlson comorbidities. PATIENTS AND
      METHODS: The automated digital algorithm was built by a series of programmatic
      queries applied to an institutional electronic medical record database. The
      automated digital algorithm was derived from secondary analysis of an
      observational cohort study of 1447 patients admitted to the intensive care unit
      from January 1 through December 31, 2006, and validated in an independent cohort
      of 240 patients. The sensitivity, specificity, and positive and negative
      predictive values of the automated digital algorithm and International
      Classification of Diseases, Ninth Revision (ICD-9) codes were compared with
      comprehensive medical record review (reference standard) for the Charlson
      comorbidities. RESULTS: In the derivation cohort, the automated digital algorithm
      achieved a median sensitivity of 100% (range, 99%-100%) and a median specificity
      of 99.7% (range, 99%-100%). In the validation cohort, the sensitivity of the
      automated digital algorithm ranged from 91% to 100%, and the specificity ranged
      from 98% to 100%. The sensitivity of the ICD-9 codes ranged from 8% for dementia
      to 100% for leukemia, whereas specificity ranged from 86% for congestive heart
      failure to 100% for leukemia, dementia, and AIDS. CONCLUSION: Our results suggest
      that search strategies that use automated electronic search strategies to extract
      Charlson comorbidities from the clinical notes contained within the electronic
      medical record are feasible and reliable. Automated digital algorithm
      outperformed ICD-9 codes in all the Charlson variables except leukemia, with
      greater sensitivity, specificity, and positive and negative predictive values.

PMID- 22958989
TI  - Low lung function and risk of type 2 diabetes in Japanese men: the Toranomon
      Hospital Health Management Center Study 9 (TOPICS 9).
AB  - OBJECTIVE: To evaluate the effect of elevated fasting plasma glucose (FPG) and
      hemoglobin A(1c) (HbA(1c)) concentrations on lung dysfunction and to
      prospectively investigate whether reduced lung function would be independently
      predictive of diabetes. PARTICIPANTS AND METHODS: From January 6, 1997, through
      December 22, 2008, we observed 5346 men with no history of diabetes or lung
      dysfunction. Hazard ratios (HRs) for incident diabetes (FPG >=126 mg/dL, HbA(1c)
      >=6.5%, or self-reported clinician-diagnosed diabetes) were estimated for
      spirometry indices as continuous and categorical variables. RESULTS: Elevated
      HbA(1c) concentrations within the normal range were significantly and more
      strongly associated with reduced forced vital capacity and forced expiratory
      volume in the first second after expiration (FEV(1)) than were FPG
      concentrations. During a 4.0-year follow-up, diabetes developed in 214
      individuals. A 10-point decrease in percentage of FEV(1) predicted value was
      associated with an increased HR of 1.21 (95% confidence interval [CI], 1.09-1.34;
      P=.001) for diabetes after adjustment for demographic factors and body mass
      index. This association remained significant even after adjustment for metabolic
      factors, smoking status, and FPG or HbA(1c) concentrations but was attenuated
      substantially after adjustment for baseline HbA(1c) values (HR, 1.13; 95% CI,
      1.01-1.26; P=.03). Lower quartile (Q) categories of percentage of FEV(1)
      predicted value were associated with increased risk of diabetes independently of
      known predictors including HbA(1c) (HR, 1.73; 95% CI, 1.14-2.62 for Q1; and HR,
      1.76; 95% CI, 1.15-2.69 for Q2). CONCLUSION: Reduced lung function was
      significantly related to chronic glycemic exposure within a normal range.
      Relatively low pulmonary function was an independent risk factor for diabetes in
      apparently healthy Japanese men.

PMID- 22958990
TI  - Effect of a primary care continuing education program on clinical practice of
      chronic obstructive pulmonary disease: translating theory into practice.
AB  - OBJECTIVES: To describe the development and implementation process and assess the
      effect on self-reported clinical practice changes of a multidisciplinary,
      collaborative, interactive continuing medical education (CME)/continuing
      education (CE) program on chronic obstructive pulmonary disease (COPD). METHODS:
      Multidisciplinary subject matter experts and education specialists used a
      systematic instructional design approach and collaborated with the American
      College of Chest Physicians and American Academy of Nurse Practitioners to
      develop, deliver, and reproduce a 1-day interactive COPD CME/CE program for 351
      primary care clinicians in 20 US cities from September 23, 2009, through November
      13, 2010. RESULTS: We recorded responses to demographic, self-confidence, and
      knowledge/comprehension questions by using an audience response system. Before
      the program, 173 of 320 participants (54.1%) had never used the Global Initiative
      for Chronic Obstructive Lung Disease recommendations for COPD. After the program,
      clinician self-confidence improved in all areas measured. In addition,
      participant knowledge and comprehension significantly improved (mean score, 77.1%
      94.7%; P<.001). We implemented the commitment-to-change strategy in courses 6
      through 20. A total of 271 of 313 participants (86.6%) completed 971 commitment
      to-change statements, and 132 of 271 (48.7%) completed the follow-up survey. Of
      the follow-up survey respondents, 92 of 132 (69.7%) reported completely
      implementing at least one clinical practice change, and only 8 of 132 (6.1%)
      reported inability to make any clinical practice change after the program.
      CONCLUSION: A carefully designed, interactive, flexible, dynamic, and
      reproducible COPD CME/CE program tailored to clinicians' needs that involves
      diverse instructional strategies and media can have short-term and long-term
      improvements in clinician self-confidence, knowledge/comprehension, and clinical
      practice.

PMID- 22958991
TI  - Suicide in the US Army.
AB  - Suicide in the US Army is a high-profile public health problem that is complex
      and poorly understood. Adding to the confusion surrounding Army suicide is the
      challenge of defining and understanding individuals/populations dying by suicide.
      Data from recent studies have led to a better understanding of risk factors for
      suicide that may be specifically associated with military service, including the
      impact of combat and deployment on increased rates of psychiatric illness in
      military personnel. The next steps involve applying these results to the
      development of empirically supported suicide prevention approaches specific to
      the military population. This special article provides an overview of suicide in
      the Army by synthesizing new information and providing clinical pearls based on
      research evidence.

PMID- 22958992
TI  - Antiepileptic drugs 2012: recent advances and trends.
AB  - There are now 24 antiepileptic drugs (AEDs) approved for use in epilepsy in the
      United States by the Food and Drug Administration. A literature search was
      conducted using PubMed, MEDLINE, and Google for all English-language articles
      that discuss newly approved AEDs and the use of AEDs in epilepsy in the United
      States from January 1, 2008, through December 31, 2011. Five new agents were
      identified that have come onto the market within the past 2 years. Moreover, 3
      trends involving AEDs have become clinically important and must be considered by
      all who treat patients with epilepsy. These trends include issues of generic
      substitution of AEDs, pharmacogenomics predicting serious adverse events in
      certain ethnic populations, and the issue of the suicide risk involving the
      entire class of AEDs. This article discusses the most recent AEDs approved for
      use in the United States and the 3 important trends shaping the modern medical
      management of epilepsy.

PMID- 22958993
TI  - Practical considerations for dysphonia caused by inhaled corticosteroids.
AB  - Inhaled corticosteroid (ICS) therapy has become standard in the treatment of
      asthma. A common local adverse effect of ICS therapy is dysphonia, which has been
      reported to affect 5% to 58% of patients. Although causes of dysphonia associated
      with ICS therapy have been underinvestigated, it may result from deposition of an
      active ICS in the oropharynx during administration, which then causes myopathy or
      a mucosal effect in the laryngopharynx. Use of ICS should be considered during
      any evaluation of dysphonia. We recommend using the lowest effective dosage of
      ICS, administering medication with a spacer, gargling, rinsing the mouth and
      washing the face after inhalation, and washing the spacer. If dysphonia develops
      despite these interventions, ICS use should be suspended until symptoms resolve,
      provided that asthma control is not compromised.

PMID- 22958994
TI  - 34-year-old woman with abdominal pain and blood-streaked diarrhea.

PMID- 22958995
TI  - Mesenchymal stromal cell infusions as rescue therapy for corticosteroid
      refractory adult autoimmune enteropathy.
AB  - Adult autoimmune enteropathy (AIE) is a rare cause of malabsorption syndrome
      unresponsive to dietary restriction. Its diagnostic hallmarks are small-bowel
      villous atrophy and antienterocyte autoantibodies. Therapy is based mainly on
      nutritional support and immunosuppression. We treated a 61-year-old woman with
      corticosteroid-refractory AIE and life-threatening malabsorption syndrome with
      systemic infusions of autologous, bone marrow-derived, mesenchymal stromal cells
      (MSCs) as rescue therapy. The MSCs were expanded ex vivo following a previously
      used Good Manufacturing Practice procedure, and 2 intravenous infusions of 1.8 *
      10(6) MSCs/kg body weight were administered 2 weeks apart. Analysis of
      circulating and mucosal regulatory T-and B-cell numbers, and of serum and
      secretory immunoglobulin levels, was performed before and after treatment. The
      MSC infusions were safe and effective, leading to disappearance of disease
      hallmarks and recovery from the life-threatening condition. Increases in mucosal
      regulatory T-cell numbers and secretory immunoglobulin levels were also observed.
      The benefit, however, was transient, and a further MSC infusion resulted in the
      same short efficacy. This case encourages the use of MSCs to treat patients with
      life-threatening, corticosteroid-refractory AIE and suggests that MSC infusion
      can attenuate, albeit transiently, the autoimmune attack.

PMID- 22958997
TI  - Commenting on ten recommendations for closing the credibility gap in reporting
      industry-sponsored clinical research.

PMID- 22958996
TI  - HIV screening in the health care setting: status, barriers, and potential
      solutions.
AB  - Thirty years into the human immunodeficiency virus (HIV) epidemic in the United
      States, an estimated 50,000 persons become infected each year: highest rates are
      in black and Hispanic populations and in men who have sex with men. Testing for
      HIV has become more widespread over time, with the highest rates of HIV testing
      in populations most affected by HIV. However, approximately 55% of adults in the
      United States have never received an HIV test. Because of the individual and
      community benefits of treatment for HIV, in 2006 the Centers for Disease Control
      and Prevention recommended routine screening for HIV infection in clinical
      settings. The adoption of this recommendation has been gradual owing to a variety
      of issues: lack of awareness and misconceptions related to HIV screening by
      physicians and patients, barriers at the facility and legislative levels, costs
      associated with testing, and conflicting recommendations concerning the value of
      routine screening. Reducing or eliminating these barriers is needed to increase
      the implementation of routine screening in clinical settings so that more people
      with unrecognized infection can be identified, linked to care, and provided
      treatment to improve their health and prevent new cases of HIV infection in the
      United States.

PMID- 22958998
TI  - Credibility of industry-sponsored clinical research: hype or hope?

PMID- 22958999
TI  - Surgical excision of invasive aspergillosis of the right ventricle presenting as
      intractable ventricular arrhythmia and right ventricular mass.

PMID- 22959001
TI  - Sir Brian Gerald Barratt-Boyes-pioneer cardiac surgeon.

PMID- 22959003
TI  - Herpes simplex encephalitis affecting the entire limbic system.

PMID- 22959004
TI  - Lipopolysaccharide from Escherichia coli but not from Porphyromonas gingivalis
      induce pro-inflammatory cytokines and alkaline phosphatase in dental follicle
      cells.
AB  - OBJECTIVES: Dental follicle cells (DFCs) as periodontal precursor cells are the
      natural source for cellular therapies of periodontitis. Periodontitis is
      initiated after the infection of the periodontium with oral pathogens such as the
      Gram-negative bacteria Porphyromonas gingivalis. Lipopolysaccharide (LPS) is the
      major component of the outer membrane of gram-negative bacteria. Previous studies
      have shown that especially P. gingivalis LPS induces the expression of pro
      inflammatory cytokines in PDL cells and disturbs the differentiation of dental
      stem cells. Our study investigated the administration of LPS to DFCs for the
      first time. MATERIALS AND METHODS: We evaluated cell proliferation (WST1 assay),
      expression of cytokines IL1beta, IL8 and IL6 (real-time RT-PCR) and the
      osteogenic differentiation of DFCs (ALP-activity and Alizarin red staining) in
      the presence of P. gingivalis LPS and Escherichia coli LPS. RESULTS: All tested
      pro-inflammatory cytokines were highly increased after E. coli LPS treatment. P.
      gingivalis LPS induces only the expression of IL8, but this expression was
      significantly lower than that after E. coli LPS administration. The ALP activity
      was significantly higher in DFCs after the administration of E. coli LPS than
      after administration of P. gingivalis LPS or under normal cell differentiation
      conditions. However, the mineralization was inhibited with LPS from both
      bacterial species. CONCLUSION: LPS disturbs osteogenic differentiation in DFCs.
      Moreover, the failure of pro-inflammatory cytokines induction in DFCs after the
      administration of P. gingivalis LPS differs greatly from that of PDL fibroblasts.
      These immunological properties of DFCs have to be considered for cellular
      therapies of periodontitis with DFCs.

PMID- 22959005
TI  - Impact of inflammatory bowel disease on post-cholecystectomy complications and
      hospitalization costs: a Nationwide Inpatient Sample study.
AB  - BACKGROUND AND AIM: Our previous single-center study showed that patients with
      underlying inflammatory bowel disease (IBD) had a higher risk for post
      cholecystectomy complications. The aim of the current population-based study was
      to verify whether concomitant IBD was indeed associated with an increased risk of
      post-cholecystectomy complications. METHODS: In this cross-sectional study, all
      1,155,432 patients from the Nationwide Inpatient Sample (NIS) with a primary
      procedure of cholecystectomy were examined, and 5891 patients with IBD were
      compared with 1,149,541 patients without IBD from 2006 to 2008. RESULTS: There
      were no significant differences in age, gender, frequency of obesity, and post
      operative mortality between the two groups. More patients in the IBD group had
      post-operative complications than the non-IBD group [398/5891 (6.8%) vs.
      55,202/1,149,541 (4.8%), p=0.002)]. On multivariate analysis, the presence of
      Crohn's disease (CD) was associated with an increased risk for post-operative
      complications (odds ratio [OR]=1.6; 95% confidence interval [CI], 1.2-2.1,
      p=0.003). The other risk factors for post-cholecystectomy complications were
      older age, male gender, African-American race, malnutrition and patients with
      higher co-morbidity index. The presence of ulcerative colitis (UC) was associated
      with a trend for increased complications (OR=1.3, 95% CI 0.8-2.1, p=0.08).
      Patients with IBD who underwent cholecystectomy incurred higher mean hospital
      costs ($39,651 vs. $35,196, p=0.006) and also stayed in the hospital 1.2 days
      longer than those without underlying IBD. CONCLUSIONS: CD patients undergoing
      cholecystectomy were shown to have a significantly increased risk for
      postoperative complications, have a longer stay in the hospital, and incur higher
      hospitalization costs.

PMID- 22959006
TI  - Role of non-structural protein 2 in the regulation of the replication of the
      porcine reproductive and respiratory syndrome virus in MARC-145 cells: effect of
      gene silencing and over expression.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an economically important
      disease in swine-producing areas. Many vaccine strategies have been developed to
      control the disease, but none have yet been completely successful. The
      development of a cell line that can produce large yields of PRRSV vaccine is very
      necessary. In order to determine the role of Nsp2 in the replication of the
      highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV)
      in MARC-145 cells, we used an RNA interference-based short hairpin RNA of Nsp2
      and constructed cell lines expressing the HP-PRRSV Nsp2 gene. Conserved HP-PRRSV
      Nsp2 sequences were used to design short interfering RNAs and test their ability
      to silence PRRSV transcript expression and replication in cells in vitro
      transfection. Nsp2, ORF7, and beta-actin mRNA expression were determined using
      semi-quantitative real-time PCR. Infection with siRNA targeting Nsp2 was found to
      reduce the Nsp2 expression in MARC-145 cells infected with PRRSV. Both MARC-145
      TJ Nsp2 and MARC-145-TJM Nsp2 cell lines were screened by G418, which were
      infected with HP-PRRSV, normal MARC-145 cells for mock, and then virus titers
      were calculated by TCID(50) after the CPE showing up. The downregulation of Nsp2
      induced a remarkable decrease in PRRSV replication, causing the reduction of
      structural protein. The Nsp2-targeted siRNA was found to downregulate the
      expression of Nsp2 in MARC-145 cells and inducing replication reduce of PRRSV in
      MARC-145 cells. The shRNA vectors S-1 and S-2 could effectively induce the
      inhibition of viral replication in MARC-145. Results showed that cells expressing
      the Nsp2 gene of the highly pathogenic PRRSV TJ and attenuated TJM remained
      stable. PRRSV replication was faster in these cells than in MARC-145 cells,
      especially during the early stage. This shows that Nsp2 plays a positive role in
      PRRSV proliferation.

PMID- 22959007
TI  - Significance of genetic variation of PRRSV ORF5 in virus neutralization and
      molecular determinants corresponding to cross neutralization among PRRS viruses.
AB  - A high rate of genetic and antigenic variability among porcine reproductive and
      respiratory syndrome viruses (PRRSVs) hampers effective prevention and control of
      the disease caused by PRRSV. The major envelope protein (GP5) encoded by the ORF5
      of PRRSV has a critical role in inducing virus neutralizing (VN) antibody and
      cross protection among different strains of PRRSV. This study was conducted to
      identify sequence elements related to cross neutralization by comparing the ORF5
      sequences of 69 field isolates in conjunction with their susceptibility to VN
      antibody raised against the VR2332 strain in vitro and in vivo. Five common
      variable sites (amino acid position 32-34, 38-39, 57-59, 137 and 151) were
      identified between susceptible and resistant viral isolates. Mutants whose ORF5
      amino acid sequences were substituted with the sequences corresponding to the 5
      identified common variable sites individually or concurrently were generated from
      a VR2332-backboned infectious clone by site mutagenesis. The change in the
      susceptibility of the mutants to VN antibodies specific for VR2332 or a
      heterologous PRRSV was assessed to determine the association of those 5
      identified sites with cross neutralization. Among the five sites, the changes of
      amino acid sequences at three sites (32-34, 38-39, and 57-59) located in the N
      terminal ectodomain of ORF5 significantly influenced the susceptibility of the
      mutant viruses to VN antibody, suggesting that sequence homology at these sites
      can be utilized as genetic markers to predict the degree of cross neutralization
      among different PRRSVs.

PMID- 22959008
TI  - Dengue hemorrhagic fever: another cause of diffuse alveolar hemorrhage in
      immunocompetent patients.

PMID- 22959009
TI  - Amperometric flow system for blood glucose determination using an immobilized
      enzyme magnetic reactor.
AB  - An amperometric flow system for glucose determination in blood serum samples
      after enzymatic reaction with glucose oxidase immobilized on magnetite covered
      with silica gel modified propylamine is described. The solid was magnetically
      retained on a mini-column and placed into the flow injection system preceding the
      amperometric detector using a modified screen printed electrode with [Fe(tris(3,5
      dimetyl-1-pyrazolyl)borate)(2)](+)[FeCl(4)](-). The variables involved in the
      system such as flow rate, enzyme concentration, injection volume and reaction
      coil length were evaluated using a Taguchi parameter design. Under optimal
      conditions, the calibration curve of glucose sample was linear between 0.24 and
      6.00 mM, and with a limit of detection of 0.08 mM. The repeatability for a 4.0mM
      glucose solution was 1.0%.The method was validated by comparing the obtained
      results to those provided by the enzymatic spectrophotometric method; no
      significant differences were observed.

PMID- 22959010
TI  - Electrochemical cell chip to detect environmental toxicants based on cell cycle
      arrest technique.
AB  - A cell-based chip was recently developed and shown to be an effective in vitro
      tool for analyzing effect of environmental toxin on target cells. However, common
      cell chips are inappropriate for the detection of multiple environmental toxins.
      Here, we fabricated a neural cell chip to detect different cellular responses
      induced by BPA (bisphenol-A) and PCB (poly chlorinated biphenyl). This approach
      was based on an electrochemical method using a cell cycle-arrest technique.
      Neural cells were synchronized at the synthesis phase by treatment with
      thymidine, which results in a sharp reduction peak when compared to
      unsynchronized cells. The fabricated chip containing 50% G1/S and 50% G2/M phase
      cells was used to determine the effects of environmental toxins on neural cancer
      cells. At the end, the cell-chips could be used to assess both BPA and PCB
      toxicity that the cells were completely synchronized at the G1/S and G2/M phase.
      The proposed neural cell chip can be a useful tool for biosensors to evaluate
      easily and sensitively multiple effects of environmental toxicants on target
      cells.

PMID- 22959011
TI  - Enhanced detection of virus particles by nanoisland-based localized surface
      plasmon resonance.
AB  - In this paper, we investigate localized surface plasmon resonance (SPR) detection
      based on nanoislands. Theoretical calculation performed with rigorous coupled
      wave analysis and analytical transfer matrix method using effective medium theory
      suggests improvement on nanoislands in the limit of detection and sensitivity
      over conventional thin film-based SPR detection. Experimental results obtained
      with non-specific detection of ambient adenovirus confirm the improvement by more
      than one order of magnitude increase in the limit of detection. The enhancement
      achieved with nanoislands was explored in connection with efficient overlap
      between target and near-field distribution produced by nanoislands.

PMID- 22959012
TI  - Reusable sensor based on high magnetization carboxyl-modified graphene oxide with
      intrinsic hydrogen peroxide catalytic activity for hydrogen peroxide and glucose
      detection.
AB  - We propose a new strategy to improve the enzyme stability, construction and
      sensitivity of a multifunctional sensor. An exfoliated graphene oxide sheet with
      carboxyl-long-chains (GO-CLC) was prepared in one step from primitive graphite
      via Friedel-Crafts acylation. Magnetic nanoparticles, glucose oxidase (GOD) and
      poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) were then incorporated to
      form an electrochemical film (SPAnH-HMGO-CLC-GOD) for the detection of hydrogen
      peroxide (H(2)O(2)) and glucose. The GO and Fe(3)O(4) have intrinsic hydrogen
      peroxide catalytic activity and the activity will be enhanced by the combination
      of SPAnH coating and induces an amplification of electrochemical reduction
      current. This response can be used as a glucose sensor by tracing the released
      H(2)O(2) after enzymatic reaction of bound GOD. Our sensor was linear within the
      range from 0.01 mM to 1mM H(2)O(2) and 0.1mM to 1.4mM glucose, with high
      sensitivities of 4340.6 MUA mM(-1) cm(-2) and 1074.6 MUA mM(-1) cm(-2),
      respectively. The relative standard deviations (RSD) were 5.4% for H(2)O(2)
      detection and 5.8% for glucose detection. The true detecting range was 0.4-40 mM
      for H(2)O(2) and 4-56 mM for glucose, which multiplied by 40-fold of dilution.
      This sensor based on the catalysis of organic SPAnH and the enzymatic activity of
      GOD can be used for both H(2)O(2) and glucose sensing in potential clinical,
      environmental and industrial applications.

PMID- 22959013
TI  - A novel fluorescent biosensor for detection of target DNA fragment from the
      transgene cauliflower mosaic virus 35S promoter.
AB  - In this paper, we reported a convenient fluorescence method for the detection of
      genetically modified organisms (GMOs). As it is known that the cauliflower mosaic
      virus (CaMV) 35S promoter is widely used in most transgenic plants (Schnurr and
      Guerra, 2000), we thus design a simple method based on the detection of a section
      target DNA (DNA-T) from the transgene CaMV 35S promoter. In this method, the full
      length guanine-rich single-strand sequences were split into fragments (Probe 1
      and 2) and each part of the fragment possesses two GGG repeats. In the presence
      of K(+) ion and berberine, if a complementary target DNA of the CaMV 35S promoter
      was introduced to hybridize with Probe 1 and 2, a G-quadruplex-berberine complex
      was thus formed and generated a strong fluorescence signal. The generation of
      fluorescence signal indicates the presence of CaMV 35S promoter. This method is
      able to identify and quantify Genetically Modified Organisms (GMOs), and it shows
      wide linear ranges from 5.0*10(-9) to 9.0*10(-7) mol/L with a detection limit of
      2.0*10(-9) mol/L.

PMID- 22959014
TI  - Label-free impedimetric thrombin sensor based on poly(pyrrole-nitrilotriacetic
      acid)-aptamer film.
AB  - A label-free and highly sensitive impedimetric aptasensor was developed based on
      electropolymerized film for the determination of thrombin. The first step is the
      electrogeneration of a poly(pyrrole-nitrilotriacetic acid) (poly(pyrrole-NTA))
      film onto the surface of electrodes followed by complexation of Cu(2+) ions.
      Then, the histidine labeled thrombin aptamer was immobilized onto the electrode
      through coordination of the histidine groups on the NTA-Cu(2+) complex. The
      aptamer sensor was applied for the detection and quantification of thrombin via
      impedimetric detection without a labeling step. A linear quantification of
      thrombin was obtained in the range 4.7*10(-12)-5.0*10(-10) mol L(-1) with a
      sensitivity of 2838 Omega/log unit (R(2)=0.9984). The impedance modulus at 0.3 Hz
      as a function of thrombin concentration was used to elaborate a similar linear
      relationship from 4.7*10(-12) to 5*10(-10) mol L(-1). In addition, aptamer
      poly(pyrrole-NTA) electrodes incubated for 40 min in aqueous solutions of bovine
      serum albumin (BSA), lysozyme and IgG (5*10(-7) mol L(-1)) did not exhibit non
      specific adsorption of proteins. Moreover, it has been demonstrated that the
      selective sensor can be regenerated several times with a good reproducibility.

PMID- 22959015
TI  - Fluorometric enzymatic autoindicating biosensor for H2O2 determination based on
      modified catalase.
AB  - Our general aim is to develop reversible optical biosensors which can be used for
      continuous monitoring. In this paper we propose a biosensor for H(2)O(2)
      determination. The bioreceptor is catalase (Cat) previously linked to a Ruthenium
      O(2)-sensitive fluorophore (Cat-Ru). It is based on the reversible H(2)O(2)
      disproportionation into O(2) and H(2)O. First, the fluorescent-enzymatic system
      was optimized for batch measurements (linear response ranges from 1*10(-4) to, at
      least, 1*10(-3) M H(2)O(2)). Because of its reversibility, the same enzyme
      aliquot can be used for performing the whole calibration step (and the subsequent
      determination). Secondly, the optical sensor was prepared by Cat-Ru
      immobilization in a polyacrylamide film. The sensor permits H(2)O(2)
      determination in a similar concentration range as in batch mode and can be used
      during at least 1 month. A mathematical model has also been developed which
      permits the effect of the experimental parameters to predict. The model also
      explains the sensor behavior if different fluorophores are used, and shows that
      the analytical signal only slightly depends on the initial concentration of the
      O(2) in the sample. Finally an alternative sensor is presented based on a
      commercially available O(2) fluorescence sensor linked to catalase. This system
      gives an analytical behavior similar to that shown for the Cat-Ru sensor.

PMID- 22959016
TI  - The utility of a high-throughput scanning biosensor in the detection of the
      pancreatic cancer marker ULBP2.
AB  - In this study, a novel high-throughput biosensor based on metal-enhanced
      fluorescence technique and harmonic intensity-modulated fluorescence technique
      was developed and demonstrated to be highly sensitive for the detection of a
      pancreatic cancer marker, UL16-binding protein 2 (ULBP2), in diluted serum.
      Experimentally, the biosensor is able to detect ULBP2 at 16-18 pg/mL in 1% BSA
      PBS and in 10-fold-diluted human serum. Compared with the limit of detection
      (LOD) of the conventional enzyme-linked immunosorbent assay (ELISA) method, the
      LOD of the proposed biosensor for ULBP2 is significantly improved by 100-fold
      under the same conditions. In addition, the proposed method uses two identical
      polyclonal antibodies for the sandwich immunoassay, simplifying the experiment in
      terms of the reagents needed. Consequently, this biosensor is a cost-effective
      tool for clinical diagnosis. We believe that the proposed high-throughput
      biosensor has great potential to become a clinical diagnostic tool for the
      detection of a pancreatic cancer marker in the near future.

PMID- 22959017
TI  - The development of DNA-based quartz crystal microbalance integrated with
      isothermal DNA amplification system for human papillomavirus type 58 detection.
AB  - To address the effect of dramatic change in temperature and viscosity during PCR
      process on quartz crystal microbalance (QCM) sensor and to increase the
      sensitivity, isothermal amplification was employed in the system. We combined
      loop-mediated isothermal amplification (LAMP) technique with QCM, called as LAMP
      QCM, for detection of high-risk human papillomavirus viral DNA type 58 (HPV-58)
      which is commonly found in Asian women. The liquid-phase LAMP-QCM prototype
      comprised the frequency counter, a temperature control device and housing of the
      quartz crystal with polished gold electrodes on both sides. QCM detection signal
      was monitored in real-time based on an avidin-biotin binding between avidin
      coated QCM surface and specific biotinylated LAMP products. Analytical
      performance was evaluated for precision, sensitivity and specificity. A plasmid
      clone containing the HPV-58 sequence was diluted from 10(6) to 1 copy and used
      for detection limit. Cut-off value was estimated at 28.8 Hz from negative viral
      template. The system could detect 100 copies with Deltaf at 34.0+/-3.6 Hz
      compared to 1000 copies detected by conventional LAMP. No cross-reaction was
      observed with other HPV types. The HPV-58 detection was compared among LAMP-QCM,
      conventional LAMP and nested PCR in 50 cervical cancer tissues. The positive rate
      of LAMP-QCM was higher than that of conventional LAMP with 100% sensitivity and
      90.5% specificity. The integrated LAMP-QCM system has improved the detection
      limit up to ten times compared to conventional LAMP with less-time consuming.

PMID- 22959019
TI  - Bilateral subdural hematoma after inadvertent dural puncture during epidural
      analgesia.
AB  - BACKGROUND: Post-dural puncture headache (PDPH) is typically a benign
      complication of dural puncture that is clinically diagnosed. It commonly presents
      as a throbbing and positional headache that occurs 24-48 h after dural puncture.
      Subdural hematomas, if unrecognized, may occur as a rare and life-threatening
      complication of dural puncture. OBJECTIVES: We aim to describe the clinical
      features and sequelae of a rare complication that may result as a consequence of
      inadvertent dural puncture that, if unrecognized, has the potential to become a
      life-threatening complication from a common procedure. CASE REPORT: We report the
      case of a previously healthy 17-year-old primigravida female who initially
      presented 4 days postpartum with clinical features and imaging studies consistent
      with PDPH. The patient's symptoms were unremitting, and within 4 weeks, she
      developed bilateral subdural hematoma. With prompt recognition and diagnosis, she
      was treated with conservative medical management and subsequently improved on
      follow-up. CONCLUSION: Patients with unremitting PDPH should prompt the clinician
      to suspect the development of subdural hematoma as a potential life-threatening
      complication of an otherwise benign condition.

PMID- 22959020
TI  - De novo kidney graft tumors: results from a multicentric retrospective national
      study.
AB  - De novo tumors in renal allografts are rare and their prevalence is
      underestimated. We therefore analyzed renal cell carcinomas arising in renal
      allografts through a retrospective French renal transplant cohort. We performed a
      retrospective, multicentric survey by sending questionnaires to all French kidney
      transplantation centers. All graft tumors diagnosed after transplantation were
      considered as de novo tumors. Thirty-two centers participated in this study.
      Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%).
      Patients were 54 men and 25 women with a mean age of 47 years old at the time of
      diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44
      tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary
      carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The
      mean time lapse between transplantation and RCC diagnosis was 131.7 months.
      Thirty-five patients underwent conservative surgery by partial nephrectomy (n =
      35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific
      survival rate was 94%. Most of these tumors were small and incidental. Most
      tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative
      treatment has been preferred each time it was feasible in order to avoid a return
      to dialysis.

PMID- 22959021
TI  - Vertical pathway targeting in cancer therapy.
AB  - Malignant cells arise from particular mutations in genes controlling cell
      proliferation, invasion, and survival. Older antineoplastic drugs were designed
      to target vital cellular processes, such as DNA maintenance and repair and cell
      division. As a result, these drugs can affect all proliferating cells and are
      associated with unavoidable toxicities. Recent discoveries in cancer research
      have identified "driver" mutations in some types of cancer, and efforts have been
      undertaken to develop drugs targeting these oncogenes. In most cases, due to
      escape mechanisms and adaptive responses, single oncogene targeting is
      insufficient to induce prolonged responses in solid tumors. Drug combinations are
      therefore used to enhance the growth inhibitory and cytotoxic effects of the
      targeted therapies. Depending on the position of additional targets within the
      signaling network, drug combinations may target either different signaling
      pathways (parallel targeting) or the same pathway at several fragile nodes
      (vertical targeting). In this review, we discuss strategies of multitarget
      inhibition with a focus on vertical signaling pathway targeting.

PMID- 22959022
TI  - Histone deacetylases (HDACs) as mediators of resistance to apoptosis in melanoma
      and as targets for combination therapy with selective BRAF inhibitors.
AB  - HDACs are viewed as enzymes used by cancer cells to inhibit tumor suppressor
      mechanisms. In particular, we discuss their role as suppressors of apoptosis in
      melanoma cells and as mediators of resistance to selective BRAF inhibitors.
      Synergistic increases in apoptosis are seen when pan-HDAC inhibitors are combined
      with selective BRAF inhibitors. Moreover, cell lines from patients with acquired
      resistance to Vemurafenib undergo PLX4720 induced apoptosis when combined with
      pan-HDAC inhibitors. The mechanisms of upregulation of HDACs and the mechanisms
      involved in HDACi reversal of resistance to apoptosis are as yet poorly
      understood.

PMID- 22959023
TI  - Targeting the tumor stroma as a novel treatment strategy for breast cancer:
      shifting from the neoplastic cell-centric to a stroma-centric paradigm.
AB  - The lack of targeted therapy for women with triple negative breast cancer demands
      a "think-outside-the-box" approach in search of novel treatment strategies.
      Although cancer drug development traditionally focused on targeting the tumor
      cell cycle, emphasis has recently shifted toward the tumor microenvironment for
      novel therapeutic and prevention strategies. The tumor microenvironment is a
      dynamic composite of cells broadly categorized as immune cells and nonimmune
      cells within a scaffold of extracellular matrix, where tumor cells thrive. Among
      the various nonimmune cell types, cancer stromal cells have emerged as critical
      players in promoting tumor proliferation, neovascularization, invasion, and
      metastasis as well as interacting with immune cells to tilt the equilibrium
      toward a tolerogenic environment that favors the tumor cells. In view of recent
      work that demonstrated that the depletion of fibroblast activation protein (FAP)
      expressing tumor stromal cells resulted in stunted tumor growth and improved
      response to tumor vaccination, the tumor microenvironment is, therefore, fertile
      ground for development of novel therapy with the potential of augmenting existing
      treatment and prevention options. In this review, we will focus on current
      evidence supporting the role of cancer associated fibroblasts (CAFs), with a
      special focus on FAP(+) stromal cells, in promoting tumor growth. The role of
      CAFs in promoting an immunosuppressive environment, which may accelerate tumor
      progression, will be discussed with the hope that therapeutics developed to
      target the "generic" tumor microenvironment may be effective for malignancies
      such as triple negative breast cancer, for which targeted therapy is not
      available to date, in the future.

PMID- 22959025
TI  - Targeted therapy for brain metastases.
AB  - The prevention and treatment of brain metastases is an increasingly important
      challenge in oncology. Improved understanding of the molecular pathogenesis of a
      number of cancers has led to the development of highly active targeted therapies
      for patients with specific oncogenic events. Such therapies include EGFR
      inhibitors for lung cancer, HER2/neu inhibitors for breast cancer, and BRAF
      inhibitors for melanoma. This review will discuss the development of these
      targeted therapy approaches, existing data about their role in the management of
      brain metastasis, and opportunities and challenges for future research in this
      critical area.

PMID- 22959026
TI  - Emerging strategies for targeting cell adhesion in multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable hematological cancer involving
      proliferation of abnormal plasma cells that infiltrate the bone marrow (BM) and
      secrete monoclonal antibodies. The disease is clinically characterized by bone
      lesions, anemia, hypercalcemia, and renal failure. MM is presently treated with
      conventional therapies like melphalan, doxorubicin, and prednisone; or novel
      therapies like thalidomide, lenalidomide, and bortezomib; or with procedures like
      autologous stem cell transplantation. Unfortunately, these therapies fail to
      eliminate the minimal residual disease that remains persistent within the
      confines of the BM of MM patients. Mounting evidence indicates that components of
      the BM-including extracellular matrix, cytokines, chemokines, and growth factors
      provide a sanctuary for subpopulations of MM. This co-dependent development of
      the disease in the context of the BM not only ensures the survival and growth of
      the plasma cells but contributes to de novo drug resistance. In addition, by
      fostering homing, angiogenesis, and osteolysis, this crosstalk plays a critical
      role in the progression of the disease. Not surprisingly then, over the past
      decade, several strategies have been developed to disrupt this communication
      between the plasma cells and the BM components including antibodies, peptides,
      and inhibitors of signaling pathways. Ultimately, the goal is to use these
      therapies in combination with the existing antimyeloma agents in order to further
      reduce or abolish minimal residual disease and improve patient outcomes.

PMID- 22959027
TI  - Targeting Notch signaling for cancer therapeutic intervention.
AB  - The Notch signaling pathway is an evolutionarily conserved, intercellular
      signaling cascade. The Notch proteins are single-pass receptors that are
      activated upon interaction with the Delta (or Delta-like) and Jagged/Serrate
      families of membrane-bound ligands. Association of ligand-receptor leads to
      proteolytic cleavages that liberate the Notch intracellular domain (NICD) from
      the plasma membrane. The NICD translocates to the nucleus, where it forms a
      complex with the DNA-binding protein CSL, displacing a histone deacetylase (HDAc)
      corepressor (CoR) complex from CSL. Components of a transcriptional complex, such
      as MAML1 and histone acetyltransferases (HATs), are recruited to the NICD-CSL
      complex, leading to the transcriptional activation of Notch target genes. The
      Notch signaling pathway plays a critical role in cell fate decision, tissue
      patterning, morphogenesis, and is hence regarded as a developmental pathway.
      However, if this pathway goes awry, it contributes to cellular transformation and
      tumorigenesis. There is mounting evidence that this pathway is dysregulated in a
      variety of malignancies, and can behave as either an oncogene or a tumor
      suppressor depending upon cell context. This chapter highlights the current
      evidence for aberration of the Notch signaling pathway in a wide range of tumors
      from hematological cancers, such as leukemia and lymphoma, through to lung, skin,
      breast, pancreas, colon, prostate, ovarian, brain, and liver tumors. It proposes
      that the Notch signaling pathway may represent novel target for cancer
      therapeutic intervention.

PMID- 22959024
TI  - Targeting the metabolic microenvironment of tumors.
AB  - The observation of aerobic glycolysis by tumor cells in 1924 by Otto Warburg, and
      subsequent innovation of imaging glucose uptake by tumors in patients with PET
      CT, has incited a renewed interest in the altered metabolism of tumors. As tumors
      grow in situ, a fraction of it is further away from their blood supply, leading
      to decreased oxygen concentrations (hypoxia), which induces the hypoxia response
      pathways of HIF1alpha, mTOR, and UPR. In normal tissues, these responses mitigate
      hypoxic stress and induce neoangiogenesis. In tumors, these pathways are
      dysregulated and lead to decreased perfusion and exacerbation of hypoxia as a
      result of immature and chaotic blood vessels. Hypoxia selects for a glycolytic
      phenotype and resultant acidification of the tumor microenvironment, facilitated
      by upregulation of proton transporters. Acidification selects for enhanced
      metastatic potential and reduced drug efficacy through ion trapping. In this
      review, we provide a comprehensive summary of preclinical and clinical drugs
      under development for targeting aerobic glycolysis, acidosis, hypoxia and hypoxia
      response pathways. Hypoxia and acidosis can be manipulated, providing further
      therapeutic benefit for cancers that feature these common phenotypes.

PMID- 22959029
TI  - Targeting the tumor stroma as a novel therapeutic approach for prostate cancer.
AB  - Interactions between epithelium and the surrounding stroma are required to
      maintain organ function. These interactions provide proliferative and migratory
      restraints that define anatomical and positional information, mediated by growth
      factors and extracellular matrix components. When cancer develops, transformed
      cells lose these constraints while stroma adapts and coevolves to support the
      "function" of the tumor. The prostate is a good example of an organ that relies
      on its surrounding stroma during normal development and cancer progression.
      Carcinoma-associated fibroblasts (CAFs) constitute a substantial volume of the
      tumor stroma and play a pivotal role in tumor maintenance, dissemination, and
      even drug resistance. The origins of CAF and the exact mechanisms by which they
      promote tumor progression are still debated. CAF acquire an activated phenotype
      quite similar to the one seen during wound repair in sites of injury. Here, we
      describe the CAF ontogeny, the similarities with activated fibroblasts during
      physiological wound repair, and potential pathways that can be targeted to
      prevent their appearance in tumors and their protumorigenic functions in cancer
      progression. A strategy to identify aspects of stromal cell biology for
      therapeutic targeting is becoming increasingly plausible, driven by the increased
      understanding of the complex interplays between the cells and tissues of which
      tumors are comprised. Several preclinical and clinical studies show that
      targeting the stroma may be a promising and attractive therapeutic option for the
      treatment of cancer and has the potential to play an increasingly prominent role
      in future treatment strategies.

PMID- 22959028
TI  - Stem-like cells and therapy resistance in squamous cell carcinomas.
AB  - Cancer stem cells (CSCs) within squamous cell carcinomas (SCCs) are hypothesized
      to contribute to chemotherapy and radiation resistance and represent potentially
      useful pharmacologic targets. Hallmarks of the stem cell phenotype that may
      contribute to therapy resistance of CSCs include quiescence, evasion of
      apoptosis, resistance to DNA damage, and expression of drug transporter pumps. A
      variety of CSC populations within SCCs of the head and neck and esophagus have
      been defined tentatively, based on diverse surface markers and functional assays.
      Stem-like self-renewal and differentiation capacities of these SCC subpopulations
      are supported by sphere formation and clonogenicity assays in vitro as well as
      limiting dilution studies in xenograft models. Early evidence supports a role for
      SCC CSCs in intrinsic therapy resistance, while detailed mechanisms by which
      these subpopulations evade treatment remain to be defined. Development of novel
      SCC therapies will be aided by pursuing such mechanisms as well as refining
      current definitions for CSCs and clarifying their relevance to hierarchical
      versus dynamic models of stemness.

PMID- 22959030
TI  - Resistance to chemotherapy: short-term drug tolerance and stem cell-like
      subpopulations.
AB  - Personalized medicine in cancer treatment has been a major goal for decades.
      Recently, the development of several therapies that specifically target key
      genetic alterations in different malignancies has dramatically improved patient
      outcome and brought the goal of personalized medicine closer to practicality.
      Despite the improved specificity of these treatment options, resistance to
      targeted therapy is common and remains a major obstacle to long-term management
      of a patient's disease. Often patient relapse is a result of the positive
      selection of cells with certain genetic alterations that result in a bypass of
      the therapeutic intervention. Once this occurs, patient relapse is inevitable and
      further treatment options are limited. The time to relapse is often quite rapid
      indicating that cancer cells may be primed for adapting to cytotoxic stimuli.
      Recently, it has been suggested that small subpopulations of cells allow
      resistance to occur more rapidly. It is thought that these cells are capable of
      surviving strong apoptotic stimuli until more permanent mechanisms of long-term
      resistance are developed. In order to decrease the rate of patient relapse, more
      studies are required in order to identify these subpopulations of cells,
      understand the mechanisms underlying their drug tolerance, and develop strategies
      to prevent them from evading treatment.

PMID- 22959031
TI  - Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma
      subpopulations.
AB  - Malignant melanoma is an aggressive form of skin cancer whose incidence continues
      to increase worldwide. Increased exposure to sun, ultraviolet radiation, and the
      use of tanning beds can increase the risk of melanoma. Early detection of
      melanomas is the key to successful treatment mainly through surgical excision of
      the primary tumor lesion. But in advanced stage melanomas, once the disease has
      spread beyond the primary site to distant organs, the tumors are difficult to
      treat and quickly develop resistance to most available forms of therapy. The
      advent of molecular and cellular techniques has led to a better characterization
      of tumor cells revealing the presence of heterogeneous melanoma subpopulations.
      The discovery of gene mutations and alterations of cell-signaling pathways in
      melanomas has led to the development of new targeted drugs that show dramatic
      response rates in patients. Single-agent therapies generally target one
      subpopulation of tumor cells while leaving others unharmed. The surviving
      subpopulations will have the ability to repopulate the original tumors that can
      continue to progress. Thus, a rational approach to target multiple subpopulations
      of tumor cells with a combination of drugs instead of single-agent therapy will
      be necessary for long-lasting inhibition of melanoma lesions. In this context,
      the recent development of immune checkpoint reagents provides an additional armor
      that can be used in combination with targeted drugs to expand the presence of
      melanoma reactive T cells in circulation to prevent tumor recurrence.

PMID- 22959033
TI  - Whole genome and exome sequencing of melanoma: a step toward personalized
      targeted therapy.
AB  - Melanoma has historically been refractive to traditional therapeutic approaches.
      As such, the development of novel drug strategies has been needed to improve
      rates of overall survival in patients with melanoma, particularly those with late
      stage or disseminated disease. Recent success with molecularly based targeted
      drugs, such as Vemurafenib in BRAF-mutant melanomas, has now made "personalized
      medicine" a reality within some oncology clinics. In this sense, tailored drugs
      can be administered to patients according to their tumor "mutation profiles." The
      success of these drug strategies, in part, can be attributed to the
      identification of the genetic mechanisms responsible for the development and
      progression of metastatic melanoma. Recently, the advances in sequencing
      technology have allowed for comprehensive mutation analysis of tumors and have
      led to the identification of a number of genes involved in the etiology of
      metastatic melanoma. As the methodology and costs associated with next-generation
      sequencing continue to improve, this technology will be rapidly adopted into
      routine clinical oncology practices and will significantly impact on personalized
      therapy. This review summarizes current and emerging molecular targets in
      metastatic melanoma, discusses the potential application of next-generation
      sequencing within the paradigm of personalized medicine, and describes the
      current limitations for the adoption of this technology within the clinic.

PMID- 22959034
TI  - Targeted therapy for gastric adenocarcinoma.
AB  - Gastric cancer (GC) is one of the leading causes of cancer death worldwide.
      Despite significant improvement in understanding disease biology and recent
      improvements in surgical outcome, radiation techniques, and chemotherapy, the 5
      year survival rates remain divsmal. Several pathways related to cell
      proliferation, invasion, and metastasis have been identified and evaluated as
      candidates for targeted treatment but despite promising preclinical data, the
      majority of targeted agents failed to improve outcome in this disease. Recently,
      adding Trastuzumab-a HER-2 monoclonal antibody-to cisplatin-based chemotherapy in
      patients with HER-2 overexpressing gastric and gastroesophageal junction (GEJ)
      adenocarcinoma resulted in statistically significant improvement in response
      rate, progression-free survival, and overall survival in phase III trial. We have
      reviewed the different pathways relevant to gastric cancer development with focus
      on the recent advances in targeting these pathways in order to improve outcomes
      in this disease.

PMID- 22959035
TI  - HSP90 inhibitors for cancer therapy and overcoming drug resistance.
AB  - Since the initial discovery of heat shock protein 90 (HSP90) as a target for
      anticancer therapy, tremendous progress has been made in developing a multitude
      of potent first- and second-generation HSP90 inhibitors. Promising activity has
      been reported with 17-AAG in combination with trastuzumab in HER2 positive breast
      cancer refractory to trastuzumab therapy and more recently in ALK-mutated lung
      cancers. However, the full potential of this class of agents is yet to be
      realized. This review not only provides an up-to-date overview of the clinical
      development of HSP90 inhibitors and their companion biomarker assays but also
      provides insight into the less-understood role of HSP90 in tumor evolution and
      drug resistance. A better understanding of these important concepts will
      facilitate the optimal and expedient development of this class of agents,
      ultimately fulfilling their promise as potent anticancer therapeutics and leading
      to the regulatory approval of the first-in-class HSP90 inhibitor.

PMID- 22959032
TI  - Chemoprevention of melanoma.
AB  - Despite advances in drug discovery programs and molecular approaches for
      identifying drug targets, incidence and mortality rates due to melanoma continue
      to rise at an alarming rate. Existing preventive strategies generally involve
      mole screening followed by surgical removal of the benign nevi and abnormal
      moles. However, due to lack of effective programs for screening and disease
      recurrence after surgical resection, there is a need for better chemopreventive
      agents. Although sunscreens have been used extensively for protecting from UV
      induced melanomas, results of correlative population-based studies are
      controversial, with certain studies suggest increased skin cancer risk in
      sunscreen users. Therefore, these studies require further authentication to
      conclusively confirm the chemoprotective efficacy of sunscreens. This chapter
      reviews the current understanding regarding melanoma chemoprevention and the
      various strategies used to accomplish this objective.

PMID- 22959036
TI  - Apoptosis in targeted therapy responses: the role of BIM.
AB  - The treatment of advanced cancer has undergone a dramatic change over the past 5
      years. Laboratory findings have led to the development of newer treatments, often
      termed "targeted therapies," which are significantly different from traditional
      chemotherapies in that they aim to disrupt critical processes needed specifically
      for a cancer cell's growth and survival, therefore, eliminating some of the
      general toxicities of chemotherapies. Cancers with specific genetic
      abnormalities, for instance epidermal growth factor receptor (EGFR) mutant lung
      cancers and HER2 amplified breast cancers, are often sensitive to these new
      targeted therapies that can specifically inhibit the function of EGFR or HER2.
      This has led to more routine prospective genetic testing of cancers to determine
      which patients should get these treatments instead of chemotherapy. However,
      emerging clinical data have revealed that some cancers with these genetic
      mutations (that predict a response) are unexpectedly not sensitive to these
      treatments. There is a growing body of evidence suggesting a deficiency in
      apoptosis following targeted therapy treatment can lead to this lack of
      sensitivity. Moreover, the pro-apoptotic protein BIM has emerged as a key
      modulator of apoptosis following effective targeted therapy, and deficiencies in
      BIM expression result in targeted therapy resistance. In this chapter, we
      summarize what is known about the role of BIM in targeted therapy-induced
      apoptosis, and discuss the implications of deficient BIM in cancers treated with
      these therapies. We highlight potential pharmaceutical strategies to overcome low
      BIM expression and sensitize these cancers to targeted therapies.

PMID- 22959037
TI  - Preface: National Cancer Act.

PMID- 22959038
TI  - Generic and rapid determination of veterinary drug residues and other
      contaminants in raw milk by ultra performance liquid chromatography-tandem mass
      spectrometry.
AB  - A generic, rapid and simple analytical method able to identify 255 veterinary
      drug residues and other contaminants in raw milk had been developed. The method
      was based on two-step simple precipitation and ultra performance liquid
      chromatography coupled with electrospray ionization and tandem mass spectrometry
      (UPLC-ESI-MS/MS) operating both in positive and negative multiple reaction mode
      (MRM). For most of the target analytes, the optimized pretreatment processes led
      to no significant interference on analysis from complicated sample matrix. For
      quantification, matrix-fortified calibration curves were performed to compensate
      for the matrix effect and loss in sample preparation. Competent linearity was
      found for over 90% of target compounds with linear regression coefficients (R)
      higher than 0.99. Detection limits ranged from 0.05 to 10MUg/kg. Average
      recoveries spiked into raw milk were in the range from 63% to 141% with
      associated RSD values from 1% to 29% under the selected conditions. The method
      had been validated for its extraction sensitivity, linearity, recoveries and
      precision. The results clearly demonstrated the feasibility of the approach
      proposed. Application of this method, which improved efficiency and coverage of
      residues, would imply a drastic reduction of both effort and time in routine
      monitoring programs.

PMID- 22959040
TI  - Review articles.

PMID- 22959039
TI  - Orthopaedic podiatry triage: process outcomes of a skill mix initiative.
AB  - BACKGROUND: The Orthopaedic Podiatry Triage Clinic (OPodTC) is a 'skill mix'
      model of care developed in Queensland Health to address the problem of lengthy
      waiting times for orthopaedic surgery on foot and ankle pathologies. It is based
      on the recognition that many orthopaedic surgery referrals can be identified
      early and treated conservatively with podiatry, averting the need for more costly
      and invasive surgical interventions. The model is collaborative and relies on
      screening and triage by the podiatrist, rather than delegation by the orthopaedic
      surgeon. METHODS: Screening and triage through OPodTC was trialled at three
      Queensland Health hospital facilities during 2009 and 2010 to improve service
      timeliness. Patients identified by the OPodTC podiatrist as suitable for
      conservative management were provided with non-surgical podiatry interventions
      and discharged if appropriate. Those identified as still requiring surgical
      intervention after the benefit of interim conservative treatment provided by the
      podiatrist (or who chose to remain on the list) were returned to their previous
      place on the orthopaedic waiting list. This paper presents a summary and
      description of waiting list changes in association with this trial. RESULTS: The
      OPodTC intervention resulted in a reduction in the non-urgent category of the
      waiting list across the three hospitals of between 23.3% and 49.7%. Indications
      from wait-list service data demonstrated increased timeliness and improved
      patient flow, which are core goals of these skill mix initiatives. CONCLUSIONS:
      This study highlights the potential of screening and triage functions in the
      skill mix debate. In this example, conservative treatment options were considered
      first, suitable patients did not have to wait long periods to receive timely and
      appropriate interventions, and those for whom surgery was indicated, were
      provided with a more targeted service.

PMID- 22959041
TI  - Guidelines for preparation of review articles.

PMID- 22959042
TI  - Laxity of the normal glenohumeral joint: A quantitative in vivo assessment.
AB  - It is critical that surgeons comprehend the normal laxity of the glenohumeral
      joint (1) to assist them in diagnosing conditions of clinical instability and (2)
      to help define a therapeutic end point for the management of shoulders with
      excessive stiffness. In clinical practice this joint laxity is judged by standard
      manual tests. We report a quantitative study of the clinical in vivo laxity of
      the normal shoulders of eight male volunteers. To our knowledge this is the first
      time that the laxity revealed on standard manual clinical tests has been
      quantified in vivo. The relative motions of the humerus and scapula were
      determined with an electromagnetic spatial tracker. This device was pinned
      percutaneously to the humerus and scapula of each of eight normal male volunteers
      of ages 25 to 45 years. An experienced shoulder surgeon carried out standard
      manual clinical tests of glenohumeral laxity while the resulting displacements of
      the humeral head relative to the glenoid were measured. Spatial tracker data
      indicated that for each of the different tests, the positions of the glenohumeral
      and scapulothoracic joints were reproducible for a given subject and among
      subjects. Substantial glenohumeral translations were measured during those manual
      laxity tests in which the joint was not at the limit of its range of motion: the
      drawer test, 7.8 +/- 4.0 mm anterior and 7.9 +/- 5.6 mm posterior; the sulcus
      test, 10.6 +/- 3.8 mm inferior; and the push-pull test, 9.0 +/- 6.3 mm posterior.
      A minimal translation of 0.3 +/- 2.5 mm was measured during the fulcrum test in
      which the glenohumeral ligaments were under tension. The observed translations
      were reproducible in each subject's shoulder. On the other hand, there was marked
      variability among subjects. Even though manual laxity tests are a standard part
      of the clinical evaluation of the shoulder, our finding that normal glenohumeral
      joints show substantial translations indicates that translation on clinical
      manual laxity testing is not in and of itself a sufficient indication for
      surgical stabilization.

PMID- 22959043
TI  - Total shoulder arthroplasty with a tissue-ingrowth glenoid component.
AB  - A newly designed, uncemented, tissue-ingrowth glenoid component with a porous
      surface was used in association with the Neer humeral head prosthesis for 32
      total shoulder arthroplasties in 29 patients. The diagnoses for the shoulders
      were osteoarthritis in 17, rheumatoid arthritis in eight, and traumatic arthritis
      in seven. Follow-up evaluations averaged 51 months (range, 29 to 80 months). Five
      complications occurred, necessitating four reoperations: two for glenoid
      component dissociation, one for humeral loosening, and one for infection. Little
      or no pain was experienced after the operation in 27 (96%) of the 28 shoulders
      that required no additional surgery. Average active abduction was 145 degrees ,
      average external rotation was 59 degrees , and median internal rotation was to
      112. Three glenoid components had probable loosening on radiographic examination.
      Eight shoulders had some degree of instability; a complication related to the
      glenoid component (polyethylene dissociation) or probable loosening not yet
      requiring reoperation developed in four of these (p < 0.02). These data support
      the continuing use of an uncemented, tissue-ingrowth glenoid component in
      arthritic shoulders with adequate bone support. Joint instability must be avoided
      to lessen complications and the need for revision surgery.

PMID- 22959044
TI  - "The color test": An intraoperative staining test for joint-side rotator cuff
      tearing and its extension.
AB  - The joint-side rotator cuff tear and its extension are usually diagnosed by
      arthrography. However, it is not always possible at surgery to determine the
      exact site and extension of the tear when one is viewing the apparently intact
      bursal floor. "The color test," an intraoperative staining test with indigo
      carmine solution or methylene blue solution, was devised and has been helpful in
      the identification of the tear in 11 (65%) of 17 joint-side rotator cuff tears.
      The test was also useful in detecting concomitant intratendinous lamination in
      pinhole and very small (less than 1 cm) full-thickness tears. The tendon sheath
      for the long head of the biceps brachii muscle and the rotator interval are two
      sites that are normally stained. They should serve for surgical orientation. An
      18-month follow-up indicates that injecting the dyes into the joints of Japanese
      monkeys appears to be harmless.

PMID- 22959045
TI  - Surgical treatment for posterior ossifications of the glenoid in baseball
      players.
AB  - Seven baseball pitchers with symptomatic posterior glenoid osteophytes were
      operated on between 1982 and 1988 and were followed for an average of 5.2 years.
      Five and two patients had ossifications on the posteroinferior glenoid rim and on
      the infraglenoid tubercle, respectively. Ossifications on the posteroinferior
      glenoid rim were associated with posterior glenohumeral impingement, posterior
      glenoid labrum tears, and axillary neuropathy. Ossifications on the infraglenoid
      tubercle were associated with axillary nerve entrapment by the osteophytes and
      the thickened long head of the triceps muscle. Histologic study showed the
      coexistence of reactive new bone formation and bone necrosis. Preoperative and
      postoperative pain, sensory loss, muscle strength, and throwing distance were
      assessed. After surgical resection of the osteophytes and release of the axillary
      nerve entrapment, improvement in all parameters was observed in all patients.

PMID- 22959046
TI  - Shoulder arthrography for determination of size of rotator cuff tear.
AB  - One hundred eight shoulder arthrograms were performed in 105 patients who
      subsequently underwent surgical repair of a rotator cuff tear. Eighty-seven were
      single-contrast arthrograms and 21 were double-contrast studies; three or more
      views were used for all shoulders. Four readers independently evaluated the
      arthrograms (two orthopaedic surgeons and two radiologists). The size of the
      rotator cuff tear could be categorized into one of four groups with accuracy in
      only 56% of the cases; however, the fear size was identified with accuracy or
      within one size category in 96% of the shoulders studied.

PMID- 22959047
TI  - Range of motion and arthrography in the frozen shoulder.
AB  - The relationship between the range of motion and the arthrographic measurements
      were assessed in 91 patients with frozen shoulders. Range of motion was recorded
      in flexion, abduction, external rotation, and internal rotation. On the
      arthrogram the following parameters were measured: depth of the axillary pouch,
      width of the anterior ballooning, extent of the subscapularis bursa, filling of
      the biceps tendon sheath, and the irregularity of the capsular outline in the
      anteroposterior view. Both the subscapularis bursa and the biceps tendon sheath
      were also assessed in the scapular Y view. There were mild correlations between
      external rotation and the anterior ballooning and between internal rotation and
      the axillary pouch, but the coefficient of determination (r-square) in each
      correlation was small. No significant correlation was observed between flexion or
      abduction and any of the arthrographic measurements. Although these arthrographic
      findings are characteristic to frozen shoulders, none of them is a good predictor
      of the severity of restricted motion.

PMID- 22959048
TI  - A system for describing positions of the humerus relative to the thorax and its
      use in the presentation of several functionally important arm positions.
AB  - The function of the shoulder is to position the arm with respect to the thorax.
      Humerothoracic positions are commonly described in terms of the degrees of
      humeral elevation in the sagittal plane (flexion) and/or the degrees of elevation
      in the coronal plane (abduction). This article proposes a more general system for
      describing positions of the arm based on the plane of humeral elevation and the
      angle of elevation within this plane. This system is used to present the
      humerothoracic positions used by eight normal subjects to perform several
      activities of daily living as well as those achieved in a range-of-motion
      examination of the shoulder. Eating, hair combing, and maximal elevation were all
      performed in a plane approximately 60 degrees  anterior to the coronal plane.
      Between reaching the perineum and washing the contralateral axilla, the humerus
      functioned in a range of planes extending over 180 degrees .

PMID- 22959049
TI  - Treatment options available for bacillus Calmette-Guerin failure in non-muscle
      invasive bladder cancer.
AB  - CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative
      treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC).
      Many patients will experience recurrence or progression following BCG and are
      termed BCG failures. OBJECTIVE: To summarise the current treatment options
      available for patients with high-risk NMIBC who experience BCG failure. EVIDENCE
      ACQUISITION: We searched the Medline, Embase, and Cochrane Trials databases for
      studies of BCG failure using predetermined relevant Medical Subject Heading terms
      and free text terms. EVIDENCE SYNTHESIS: Radical cystectomy (RC) should be
      strongly recommended when a patient has been deemed to fail BCG, if the patient
      is fit and fully informed of the risks, benefits, and quality-of-life issues. RC
      achieves long-term survival in excess of 90% with ongoing improvements in
      morbidity. While other salvage intravesical therapies have to be considered
      oncologically inferior to RC, several options are now available if bladder
      preservation is the objective. The options can be categorised as immunotherapy,
      chemotherapy, device-assisted therapy, and sequential combinations of these newer
      modalities with conventional therapy. Some agents have shown specific promise in
      BCG-failure patients (eg, gemcitabine, thermochemotherapy, taxane chemotherapy),
      and some modalities have been shown to be effective only in non-BCG-failure
      cohorts (eg, electromotive mitomycin). CONCLUSIONS: The definition, prediction,
      and treatment of BCG failure remain unclear secondary to inconsistent studies and
      the heterogeneous entity of patients with NMIBC. RC should be the default
      position upon failing BCG, but if bladder preservation is sought, then several
      promising intravesical salvage options are available. It will be necessary to
      individually tailor the management of such patients based on tumour risk and
      medical profiles. Currently data are still inadequate to formulate definitive
      recommendations, and larger studies of salvage intravesical agents are urgently
      required.

PMID- 22959050
TI  - Eraser laser enucleation of the prostate: technique and results.
AB  - BACKGROUND: Eraser, a 1318-nm diode laser, has been used for 15 yr for resection
      of lung metastases. It was recently introduced in urology for small kidney tumors
      and for the treatment of benign prostatic obstruction. OBJECTIVE: To demonstrate
      on video our technique of Eraser laser enucleation of the prostate (ELEP) and
      report our experience. DESIGN, SETTING, AND PARTICIPANTS: From June 2010 to
      October 2011, 43 consecutive patients were prospectively evaluated. All of them
      had lower urinary tract symptoms suggestive of benign prostatic obstruction and a
      mean prostate size of 59.9 ml (range: 34-89 ml) on transrectal ultrasound. Their
      mean prostate-specific antigen value was 3.4 ng/ml (range: 0.8-5.0 ng/ml); mean
      maximum flow rate (Q(max)), 6.9 ml/s (range: 2-11 ml/s); mean International
      Prostate Symptom Score (IPSS), 25.9 (range: 18-32); and mean postvoid residual
      (PVR), 170.5 ml (range: 60-330 ml). SURGICAL PROCEDURE: The details of the
      technique are shown on video. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Success was defined as patients being able to void with improved IPSS, Q(max),
      PVR volume, and ameliorated quality of life. RESULTS AND LIMITATIONS: The mean
      operating time was 67.0 +/- 11.43 min. Mean serum hemoglobin was 15.1 +/- 0.87
      g/l before, and 14.39+/-0.94g/l after surgery. Mean blood loss was 115.90 +/-
      98.12 ml. No blood transfusions were required. All patients had their catheters
      removed within 2 d and were able to void spontaneously after this time.
      Significant improvements were noted in Q(max), quality of life, IPSS, and PVR
      volume from baseline to each follow-up time point. Based on the validated Clavien
      Dindo system, we observed one grade 1d complication, one grade 2 complication,
      and one grade 3b complication. CONCLUSIONS: ELEP is a safe and reproducible
      method for relieving bladder outflow obstruction and lower urinary tract
      symptoms. Its advantages include minimal blood loss, short catheterization time,
      and a brief hospital stay.

PMID- 22959051
TI  - alpha-Blockers and antimuscarinics for male lower urinary tract symptoms: the
      search goes on.

PMID- 22959052
TI  - Effectiveness of continuous passive motion in an inpatient rehabilitation
      hospital after total knee replacement: a matched cohort study.
AB  - OBJECTIVE: To examine the use of continuous passive motion (CPM) as an adjunct to
      physical therapy after total knee replacement in patients who were transferred to
      an inpatient rehabilitation facility (IRF) and to compare the effectiveness of
      CPM on active range of motion (AROM), functional tasks, destination after
      discharge, the need for home care services, and the ambulation device at
      discharge. DESIGN: Matched cohort study. SETTING: IRF. PARTICIPANTS: Patients
      admitted to a rehabilitation setting after total knee replacement surgery with an
      initial AROM for knee flexion of less than 75 degrees  at admission to the IRF.
      From this initial population, a matched sample of 61 patient pairs was included
      in the analysis (61 who used the CPM and 61 who did not receive the adjunct
      therapy). INTERVENTION: Use of CPM for 2 hours per day as an adjunct to the 3
      hours of physical and occupational therapy customary in an IRF. MAIN OUTCOMES:
      Primary outcomes were discharge active knee flexion ROM and flexion gain.
      Secondary outcomes were motor, cognitive, and total Functional Independence
      Measure scores; discharge ambulation device; destination after discharge; and the
      need for home care services after the inpatient stay. RESULTS: The outcome
      variables of 61 matched pairs of CPM users and non-CPM users were reported. No
      statistically significant differences were found in any of the outcome variables
      that were compared in this matched case design, including AROM knee, flexion
      gain, discharge to the community, need for home care services after discharge,
      and discharge with cane/no device. No significant difference was found in all
      functional scores as measured by the Functional Independence Measure scale.
      CONCLUSION: For this population, we determined at one facility that less than 30%
      are provided with a CPM as an adjunct to physical therapy. Using a matched cohort
      design, we compared CPM use with non-CPM use and determined that the application
      of CPM may not significantly influence ROM gain.

PMID- 22959053
TI  - Incidence and risk factors of poststroke falls after discharge from inpatient
      rehabilitation.
AB  - OBJECTIVE: To investigate the incidence of falls and risk factors for falls in
      persons who had a stroke. DESIGN: Telephone survey. SETTING: Tertiary university
      hospital. PATIENTS AND METHODS: Patients who had a stroke and were admitted to
      the rehabilitation unit between April 2006 and July 2008 were listed and
      contacted by telephone from February 2009 to August 2009. MAIN OUTCOME
      MEASUREMENTS: Information obtained from the interviews, which were performed 20
      +/- 8 months after discharge from inpatient rehabilitation, included demographic
      data, information about falls, and current ambulatory function. After the
      telephone interview, medical records of participants during admission were
      reviewed. RESULTS: Of the 404 enrolled patients, 330 were included in the
      analysis. Of the 330 patients, 62 (19%) had a history of a fall after stroke
      onset. Of 222 ambulatory patients, 51 patients (23%) fell. Falls frequently
      occurred in winter, and most falls occurred indoors (70%). Twenty-nine percent of
      patients experienced repeated falls. About half of those who fell were injured,
      and 11% sustained fractures. Patients who had a stroke and had severe deficits
      showed a lower probability of poststroke falls. In a subgroup analysis of
      patients with ambulatory capacity, left-sided hemiplegia/hemiparesis was
      associated with an increased risk of falls. CONCLUSIONS: This study reveals a
      high incidence of poststroke falls after discharge from inpatient rehabilitation.
      More caution should be taken for patients with ambulatory ability and left
      hemiplegia/hemiparesis because they are more vulnerable to falls after a stroke.
      An increased prevalence of fear of falling in people who fell suggests that an
      appropriate intervention to reduce fear of falling should be provided to patients
      who have had a stroke.

PMID- 22959054
TI  - Resveratrol attenuates oxidative stress and prevents steatosis and hypertension
      in obese rats programmed by early weaning.
AB  - We hypothesized that resveratrol, a natural phytoalexin found in grapes, can
      prevent oxidative stress, obesity and its related disturbances in obese rats
      programmed by early weaning. Lactating Wistar rats were separated into two
      groups: early weaning (EW) - dams who were wrapped with a bandage to interrupt
      the lactation in the last 3 days of lactation; control - dams whose pups had free
      access to milk during all lactation. At the 150th day, EW offspring were randomly
      subdivided into EW+resveratrol (EW+Res) - resveratrol (30 mg/kg/day); EW+vehicle
      (EW) - rats that received 0.5% (w/v) aqueous methylcellulose. The control group
      received vehicle. Rats were treated by gavage daily for 30 days. EW offspring
      developed hyperphagia, higher body weight, visceral obesity, higher systolic
      (SBP) and diastolic blood pressure (DBP) (+15% and +20%, respectively; P<.05) and
      higher serum triglycerides (TG) and low-density lipoprotein but lower high
      density lipoprotein (+55%, +33% and -13%, respectively; P<.05). Resveratrol
      normalized food intake, SBP and DBP and prevented obesity and dyslipidemia in
      EW+Res. EW rats had higher plasma and liver thiobarbituric-acid-reactive
      substances (TBARS) and lower plasma superoxide dismutase (SOD) and liver
      glutathione peroxidase activities (+51%, +18%, -58%, -31%, respectively; P<.05),
      and resveratrol normalized both plasma and liver TBARS and increased the activity
      of SOD and catalase in plasma. EW rats presented liver steatosis and higher liver
      TG, and resveratrol prevented these hepatic alterations. In conclusion, this
      study demonstrated a potential therapeutic use of resveratrol in preventing
      obesity and oxidative stress and reducing the risk of hypertension, dyslipidemia
      and steatosis in adult rats programmed by early weaning.

PMID- 22959055
TI  - Intrauterine growth restriction alters the hepatic proteome in fetal pigs.
AB  - Intrauterine growth restriction (IUGR) is a major problem in both humans and
      animals. The IUGR fetus has abnormal metabolism of nutrients in the liver. This
      study was conducted with comparative proteomic approach and biochemical analyses
      to test the hypothesis that IUGR alters the hepatic proteome in the fetal liver.
      Livers were obtained from IUGR and normal-weight fetal pigs at Day 110 of
      gestation. Twenty-two differentially expressed proteins in the liver were
      identified between IUGR and normal fetal pigs. These proteins participate in the
      intermediary metabolism of nutrients (including glucose, amino acids, protein,
      lipids, vitamins and minerals), oxidative stress, as well as cell structure and
      growth. Of particular interest, the IUGR fetus had a higher activity of glutamate
      oxaloacetate transaminase and a lower activity of lipoprotein lipase than the
      normal ones. These results indicate altered metabolism of nutrients, abnormal
      ammonia utilization, and reduced capacity for detoxification in the liver of IUGR
      fetus. Collectively, the findings have important implication for explaining low
      food efficiency and understanding the mechanism responsible for impaired growth
      in IUGR neonates.

PMID- 22959056
TI  - Epigallocatechin-3-gallate prevents systemic inflammation-induced memory
      deficiency and amyloidogenesis via its anti-neuroinflammatory properties.
AB  - Neuroinflammation has been known to play a critical role in the pathogenesis of
      Alzheimer's disease (AD) through amyloidogenesis. In a previous study, we found
      that systemic inflammation by intraperitoneal (ip) injection of
      lipopolysaccharide (LPS) induces neuroinflammation and triggers memory
      impairment. In this present study, we investigated the inhibitory effects of
      epigallocatechin-3-gallate (EGCG) on the systemic inflammation-induced
      neuroinflammation and amyloidogenesis as well as memory impairment. ICR mice were
      orally administered with EGCG (1.5 and 3 mg/kg) for 3 weeks, and then the mice
      were treated by ip injection of LPS (250 MUg/kg) for 7 days. We found that
      treatment of LPS induced memory-deficiency-like behavior and that EGCG treatment
      prevented LPS-induced memory impairment and apoptotic neuronal cell death. EGCG
      also suppressed LPS-induced increase of the amyloid beta-peptide level and the
      expression of the amyloid precursor protein (APP), beta-site APP cleaving enzyme
      1 and its product C99. In addition, we found that EGCG prevented LPS-induced
      activation of astrocytes and elevation of cytokines including tumor necrosis
      factor-alpha, interleukin (IL)-1beta, macrophage colony-stimulating factor,
      soluble intercellular adhesion molecule-1 and IL-16, and the increase of
      inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase
      2, which are known factors responsible for not only activation of astrocytes but
      also amyloidogenesis. In the cultured astrocytes, EGCG also inhibited LPS-induced
      cytokine release and amyloidogenesis. Thus, this study shows that EGCG prevents
      memory impairment as well as amyloidogenesis via inhibition of neuroinflammatory
      related cytokines released from astrocytes and suggests that EGCG might be a
      useful intervention for neuroinflammation-associated AD.

PMID- 22959057
TI  - Therapeutic effect of organoselenium dietary supplementation in a sporadic
      dementia of Alzheimer's type model in rats.
AB  - It is known that selenium (Se) might play different roles in the progression of
      Alzheimer's disease (AD), but there is a lack of evidence that proves whether
      supplementation with Se is beneficial or not for the treatment of AD. Thus, the
      aim of the current study was to investigate the therapeutic effect of p,p'
      methoxyl-diphenyl diselenide [(MeOPhSe)(2)], an organoselenium compound, against
      streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type (SDAT) in
      rats. Male Wistar rats received STZ twice daily (1.0 mg/8 MUl; 4 MUl/ventricle)
      for 21 days. After 21 days of STZ injection, regular-diet-fed rats were
      supplemented with 10 ppm of (MeOPhSe)(2) during 30 days. At the end of this
      period, the rats were challenged in the Morris water maze and step-down passive
      avoidance tasks. The activity of acetylcholinesterase (AChE), deficit in cerebral
      energy metabolism (measurement of adenosine 5-triphosphate and adenosine 5
      diphosphate levels), and oxidative and nitrosative stress were determined in the
      cortex and hippocampus of rats. The results demonstrated that (MeOPhSe)(2)
      dietary supplementation reverted STZ-induced memory impairment of rats in both
      cognitive tasks. The findings also indicated that (MeOPhSe)(2) dietary
      supplementation reverted oxidative stress in the STZ group (decreased reactive
      species and tyrosine nitration levels and enhanced nonprotein thiol levels).
      Moreover, (MeOPhSe)(2) dietary supplementation normalized AChE activity, which
      was enhanced by STZ injection, but did not revert the deficit in cerebral energy
      metabolism caused by STZ. The results of the present study indicated the
      therapeutic effect of the (MeOPhSe)(2)-supplemented diet in a rat model of SDAT.

PMID- 22959058
TI  - Postprandial changes in the proteome are modulated by dietary fat in patients
      with metabolic syndrome.
AB  - Metabolic syndrome is a multicomponent disorder whose etiology is the result of a
      complex interaction between genetic, metabolic and environmental factors
      including dietary habits. Our aim was to identify proteome-diet interactions
      during the postprandial state after the acute intake of four meals with different
      qualities of fat in the proteome of peripheral blood mononuclear cells. A
      randomized controlled trial conducted within the LIPGENE study assigned 39
      metabolic syndrome patients to one of four meals: a high-saturated-fatty-acid
      (HSFA) meal, a high-monounsaturated-fatty-acid (HMUFA) meal and two high
      polyunsaturated-fatty-acid (from walnut) (HPUFA) meals supplemented with n-3 PUFA
      or placebo. We analyzed the postprandial changes in the whole proteome of both
      nuclear and cytoplasmic fractions of peripheral blood mononuclear cells by two
      dimensional proteomics. Twenty-three proteins were differentially expressed. HSFA
      intake caused the postprandial increase of proteins responding to oxidative
      stress (HSPA1A, PDIA3 and PSME1) and DNA damage (SMC6), whereas HMUFA intake led
      to the up-regulation of HSPA1A and PDIA3. HPUFA meal supplementation with n-3
      PUFA produced peroxisomal beta-oxidation inhibition by down-regulation of ECH1, a
      process related to insulin signaling improvement. In conclusion, HSFA meal intake
      causes deleterious postprandial changes in the proteome in terms of DNA damage
      and procoagulant state, which reflect a higher postprandial oxidative stress
      after HSFA meal intake as compared to intake of HMUFA and HPUFA meals. Moreover,
      the addition of long-chain n-3 PUFA to an HPUFA meal may improve insulin
      signaling and exerts an anti-inflammatory effect when compared to an HPUFA meal.

PMID- 22959059
TI  - (-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial
      adenocarcinoma cells via ROS generation and p38 MAP kinase activation.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has
      been shown to inhibit carcinogenesis of various tumor types. The aim of this
      study was to elucidate the antiproliferative potential of EGCG and its mechanism
      in human endometrial cancer cells (Ishikawa cells) and primary endometrial
      adenocarcinoma cells. The antiproliferative effect of EGCG was evaluated by cell
      viability assay. Apoptosis was measured by annexin/propidium iodide staining.
      Reactive oxygen species (ROS) generation was measured by using 2',7'
      dichlorofluorescin diacetate dye. Expression of mitogen-activated protein
      kinases, proliferation and apoptotic markers were measured by immunoblot
      analysis. EGCG was found to inhibit proliferation in Ishikawa as well as in
      primary endometrial adenocarcinoma cells and effectively down-regulated the
      expression of proliferation markers, i.e., estrogen receptor alpha, progesterone
      receptor, proliferating cell nuclear antigen and cyclin D1. EGCG also decreased
      the activation of ERK and downstream transcription factors fos and jun. EGCG
      caused apoptotic cell death accompanied by up-regulation of proapoptotic Bax and
      down-regulation of antiapoptotic protein Bcl2. EGCG induced the cleavage of
      caspase-3 and poly(ADP-ribose) polymerase, the hallmark of apoptosis. EGCG
      significantly induced the ROS generation as well as p38 activation in Ishikawa
      cells, which appeared to be a critical mediator in EGCG-induced apoptosis. The
      apoptotic effect of EGCG and the p38 activation were blocked by pretreatment of
      cells with the ROS scavenger N-acetylcysteine. EGCG reduced the glutathione
      levels, which might be responsible for enhanced ROS generation causing oxidative
      stress in endometrial cancer cells. Taken together, these results suggest that
      EGCG inhibits cellular proliferation via inhibiting ERK activation and inducing
      apoptosis via ROS generation and p38 activation in endometrial carcinoma cells.

PMID- 22959060
TI  - Recognition of delirium on pediatric hospital services.
AB  - OBJECTIVE: Identify the frequency with which pediatric care teams recognize
      delirium in patients referred for psychiatric consultation, whether their
      diagnosis is substantiated by the involved consultant, and whether this diagnosis
      is documented in the discharge problem list. METHODS: A retrospective chart
      review was conducted on all inpatient children receiving consultation from the
      Child and Adolescent Psychiatry service between 2003 and 2011. Additionally, the
      problem lists of all inpatient pediatric discharges during that period were
      examined for the diagnosis of "delirium" or "encephalopathy". RESULTS: Six of the
      515 children referred to psychiatry for any reason were diagnosed with delirium
      by the pediatric team. The diagnosis was confirmed by psychiatry in all cases. An
      additional 47 cases of delirium were diagnosed by psychiatry in this same cohort,
      a condition never mentioned in the pediatric chart. Only 8 of the total 53
      patients (15.1%) diagnosed with delirium by pediatrics and/or psychiatry had this
      condition listed in the discharge problem list. Overall, diagnoses of delirium or
      encephalopathy were included in only 89 of the total 64,046 problem lists for any
      pediatric discharge. CONCLUSIONS: Delirium was not noted or mentioned in 88.7% of
      delirious patients referred for psychiatric consultation, potentially because it
      was never diagnosed by pediatrics. There is a low documentation rate of this
      condition on the discharge problem list, even in those children so diagnosed by
      pediatrics. These findings highlight the important role of the consultation
      psychiatrist as an educator as well as a diagnostician.

PMID- 22959061
TI  - Response to: Pseudopseudoseizures: conditions that may mimic psychogenic non
      epileptic seizures.

PMID- 22959062
TI  - Morgellons disease: more questions than answers.

PMID- 22959064
TI  - Pneumonitis post-haematopoeitic stem cell transplant - cytopathology clinches
      diagnosis.
AB  - BACKGROUND: Primary BK virus (BKV) infection is probably acquired by the
      respiratory route in childhood, and latent virus persists principally in the
      urinary tract. BKV reactivation is implicated in late onset haemorrhagic cystitis
      (HC) post Haematopoietic Stem Cell Transplant (HSCT). There is emerging evidence
      that BKV can cause life-threatening pneumonitis in immunocompromised individuals.
      OBJECTIVES: To describe the first known case of BKV pneumonitis in an adult HSCT
      recipient. STUDY DESIGN/RESULTS: A 19-year old male underwent an ABO
      incompatible, volunteer unrelated donor allogeneic HSCT for high risk AML. The
      post-transplant period was complicated by moderate-severe cutaneous and gut acute
      graft-versus-host disease (aGVHD) and severe HC, attributable to BKV. Treatment
      encompassed intensification of immunosupression for aGVHD and weekly intravenous
      (IV) cidofovir (2.5mg/Kg) for BK viruria. He was readmitted with presumed septic
      shock and acute renal failure. After a transient improvement on broad spectrum
      antibacterials, he suffered significant respiratory deterioration. CT imaging
      revealed diffuse 'ground-glass' attenuation. Cytopathological assessment of a
      broncho-alveolar sample (BAL) was consistent with polyomavirus pneumonitis. No
      other cause was found to account for the respiratory deterioration. He did not
      respond to therapy and died of multi-organ failure. CONCLUSIONS: BKV is
      implicated in haemorrhagic cystitis in HSCT recipients but not routinely
      considered as a cause of pneumonitis. There are just 5 other cases in the
      literature, including 3 patients with AIDS. BKV should be considered as a
      possible cause of pneumonitis in HSCT recipients.

PMID- 22959065
TI  - Kidney pulmonary hypertension: another road on the map?

PMID- 22959066
TI  - The effect of active pedaling combined with electrical stimulation on spinal
      reciprocal inhibition.
AB  - OBJECTIVE: Pedaling is widely used for rehabilitation of locomotion because it
      induces muscle activity very similar to locomotion. Afferent stimulation is
      important for the modulation of spinal reflexes. Furthermore, supraspinal
      modulation plays an important role in spinal plasticity induced by electrical
      stimulation. We, therefore, expected that active pedaling combined with
      electrical stimulation could induce strong after-effects on spinal reflexes.
      DESIGN: Twelve healthy adults participated in this study. They were instructed to
      perform 7 min of pedaling. We applied electrical stimulation to the common
      peroneal nerve during the extension phase of the pedaling cycle. We assessed
      reciprocal inhibition using a soleus H-reflex conditioning-test paradigm. The
      magnitude of reciprocal inhibition was measured before, immediately after, 15 and
      30 min after active pedaling alone, electrical stimulation alone and active
      pedaling combined with electrical stimulation (pedaling + ES). RESULTS: The
      amount of reciprocal inhibition was significantly increased after pedaling + ES.
      The after-effect of pedaling + ES on reciprocal inhibition was more prominent and
      longer lasting compared with pedaling or electrical stimulation alone.
      CONCLUSIONS: Pedaling + ES could induce stronger after-effects on spinal
      reciprocal inhibitory neurons compared with either intervention alone. Pedaling +
      ES might be used as a tool to improve locomotion and functional abnormalities in
      the patient with central nervous lesion.

PMID- 22959067
TI  - Modified lipoproteins provide lipids that modulate dendritic cell immune
      function.
AB  - Both physiological and pathological situations can result in biochemical changes
      of low-density lipoproteins (LDL). Because they can deliver signals to dendritic
      cells (DC), these modified lipoproteins now appear as regulators of the immune
      response. Among these modified lipoproteins, oxidized LDL (oxLDL) that accumulate
      during inflammatory conditions have been extensively studied. Numerous studies
      have shown that oxLDL induce the maturation of DC, enhancing their ability to
      activate IFNgamma secretion by T cells. LDL treated by secreted phospholipase
      A(2) also promote DC maturation. Among the bioactive lipids generated by
      oxidation or phospholipase treatment of LDL, lysophosphatidylcholine (LPC) and
      some saturated fatty acids induce DC maturation whereas some unsaturated fatty
      acids or oxidized derivatives have opposite effects. Among other factors, the
      nuclear receptor peroxisome-proliferator activated receptor gamma (PPARgamma)
      plays a crucial role in this regulation. Non-modified lipoproteins also
      contribute to the regulation of DC function, suggesting that the balance between
      native and modified lipoproteins, as well as the biochemical nature of the LDL
      modifications, can regulate the activation threshold of DC. Here we discuss two
      pathological situations in which the impact of LDL modifications on inflammation
      and immunity could play an important role. During atherosclerosis, modified LDL
      accumulating in the arterial intima may interfere with DC maturation and
      function, promoting a Th1 immune response and a local inflammation favoring the
      development of the pathology. In patients chronically infected, the hepatitis C
      virus (HCV) interferes with lipoprotein metabolism resulting in the production of
      infectious modified lipoproteins. These lipo-viral-particles (LVP) are modified
      low-density lipoproteins containing viral material that can alter DC maturation
      and affect specific toll-like receptor signaling. In conclusion, lipoprotein
      modifications play an important role in the regulation of immunity by delivering
      signals of danger to DC and modulating their function.

PMID- 22959068
TI  - Chronic gastric ulceration causes matrix metalloproteinases-9 and -3
      augmentation: alleviation by melatonin.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable
      of degradation of extracellular matrix (ECM) and key player in various
      inflammatory diseases. We investigated the regulation of MMPs in chronic gastric
      ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin
      and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N
      acetyl-5-methoxytryptamine) treatment has also been applied to mice to
      characterize the changes in expression and activities of MMPs in gastric tissues.
      We observed significant upregulation of MMP-9 and -3 expressions and activities
      in stomach with increasing doses and duration of indomethacin that corroborated
      with increased activity of activator protein (AP)-1. Substantial damage in
      gastric epithelial layer was found during chronic ulceration. Melatonin
      suppressed MMP-9 and -3 expressions and activities during prevention and healing
      of chronic gastric ulcers. It also suppressed protein oxidation, lipid
      peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 was significantly high in
      ulcerated stomachs while melatonin treatment blocked them to control level. We
      found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c
      Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were
      significantly reversed by melatonin. Moreover, expression of NF-kappaB, c-fos and
      c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3
      expressions. In summary, oxidative stress is preceded by chronic inflammation
      that enhances the expression of MMP-9 and -3, while melatonin arrests both of
      them via reduction of AP-1 activity during protection of ulcer.

PMID- 22959070
TI  - Multidisciplinary management of a hepatic and renal transplant patient with
      Alagille syndrome.

PMID- 22959071
TI  - Comparison of fetal heart rate patterns using nonlinear dynamics in breech versus
      cephalic presentation at term.
AB  - BACKGROUND: It has been reported that breech fetuses have inferior neurological
      outcomes regardless of mode of delivery, raising the possibility that in utero
      neurological impairment is more frequent in breech fetuses, possibly contributing
      to malpresentation. AIMS: To assess differences between the cardiovascular
      autonomic nervous systems (ANSs) of breech and cephalic fetuses using nonlinear
      dynamic indices of fetal heart rate (FHR) variability. STUDY DESIGN AND SUBJECTS:
      This study included 86 fetuses with breech presentation and 173 fetuses with
      cephalic presentation, with no other maternal or fetal problems. We analyzed FHR
      variability and spectral indices as markers of ANS behavior. We used nonlinear
      dynamic indices to represent the complexity of heart rate regulation, as well as
      correlation dimension as a chaotic index of the cardiovascular control system.
      RESULTS: One of FHR parameters (Mean minute range) was significantly lower in
      breech than cephalic fetuses (p=0.0294). However, there were no other significant
      differences in any linear or nonlinear indices, nor in clinical outcomes, between
      breech and cephalic fetuses. CONCLUSION: Our data suggest that breech fetuses
      have neither more active ANS nor less active complexity control systems than do
      cephalic fetuses. This indicates that the neurologic maturation of breech fetuses
      is not inferior to cephalic ones. The practical implication of these findings is
      that the nervous system integrity of breech fetuses may not result directly in
      neonatal complications.

PMID- 22959072
TI  - GIS-based models for water quantity and quality assessment in the Jucar River
      Basin, Spain, including climate change effects.
AB  - This paper describes two different GIS models - one stationary (GeoImpress) and
      the other non-stationary (Patrical) - that assess water quantity and quality in
      the Jucar River Basin District, a large river basin district (43,000km(2))
      located in Spain. It aims to analyze the status of surface water (SW) and
      groundwater (GW) bodies in relation to the European Water Framework Directive
      (WFD) and to support measures to achieve the WFD objectives. The non-stationary
      model is used for quantitative analysis of water resources, including long-term
      water resource assessment; estimation of available GW resources; and evaluation
      of climate change impact on water resources. The main results obtained are the
      following: recent water resources have been reduced by approximately 18% compared
      to the reference period 1961-1990; the GW environmental volume required to
      accomplish the WFD objectives is approximately 30% of the GW annual resources;
      and the climate change impact on water resources for the short-term (2010-2040),
      based on a dynamic downscaling A1B scenario, implies a reduction in water
      resources by approximately 19% compared to 1990-2000 and a reduction of
      approximately 40-50% for the long-term (2070-2100), based on dynamic downscaling
      A2 and B2 scenarios. The model also assesses the impact of various fertilizer
      application scenarios on the status of future GW quality (nitrate) and if these
      future statuses will meet the WFD requirements. The stationary model generates
      data on the actual and future chemical status of SW bodies in the river basin
      according to the modeled scenarios and reflects the implementation of different
      types of measures to accomplish the Urban Waste Water Treatment Directive and the
      WFD. Finally, the selection and prioritization of additional measures to
      accomplish the WFD are based on cost-effectiveness analysis.

PMID- 22959073
TI  - Quantification of reductions in ammonia emissions from fertiliser urea and animal
      urine in grazed pastures with urease inhibitors for agriculture inventory: New
      Zealand as a case study.
AB  - Urea is the key nitrogen (N) fertiliser for grazed pastures, and is also present
      in excreted animal urine. In soil, urea hydrolyses rapidly to ammonium (NH4(+))
      and may be lost as ammonia (NH3) gas. Unlike nitrous oxide (N2O), however, NH3 is
      not a greenhouse gas although it can act as a secondary source of N2O, and hence
      contribute indirectly to global warming and stratospheric ozone depletion.
      Various urease inhibitors (UIs) have been used over the last 30 years to reduce
      NH3 losses. Among these, N-(n-butyl) thiophosphoric triamide (nBTPT), sold under
      the trade name Agrotain(r), is currently the most promising and effective when
      applied with urea or urine. Here we conduct a critical analysis of the published
      and non-published data on the effectiveness of nBTPT in reducing NH3 emission,
      from which adjusted values for FracGASF (fraction of total N fertiliser emitted
      as NH3) and FracGASM (fraction of total N from, animal manure and urine emitted
      as NH3) for the national agriculture greenhouse gas (GHG) inventory are
      recommended in order to provide accurate data for the inventory. We use New
      Zealand as a case study to assess and quantify the overall reduction in NH3
      emission from urea and animal urine with the application of UI nBTPT. The
      available literature indicates that an application rate of 0.025% w/w (nBTPT per
      unit of N) is optimum for reducing NH3 emissions from temperate grasslands. UI
      treated urine studies gave highly variable reductions (11-93%) with an average of
      53% and a 95% confidence interval of 33-73%. New Zealand studies, using UI
      treated urea, suggest that nBTPT (0.025% w/w) reduces NH3 emissions by 44.7%, on
      average, with a confidence interval of 39-50%. On this basis, a New Zealand
      specific value of 0.055 for FracGASF FNUI (fraction of urease inhibitor treated
      total fertiliser N emitted as NH3) is recommended for adoption where urea
      containing UI are applied as nBTPT at a rate of 0.025% w/w. Only a limited number
      of published data sets are available on the effectiveness of UI for reducing NH3
      losses from animal urine-N deposited during grazing in a grazed pasture system.
      The same can be said about mixing UI with urine, rather than spraying UI before
      or after urine application. Since it was not possible to accurately measure the
      efficacy of UI in reducing NH3 emissions from animal urine-N deposited during
      grazing, we currently cannot recommend the adoption of a FracGASM value adjusted
      for the inclusion of UI.

PMID- 22959074
TI  - Posttransplant de novo donor-specific hla antibodies identify pediatric kidney
      recipients at risk for late antibody-mediated rejection.
AB  - The emerging role of humoral immunity in the pathogenesis of chronic allograft
      damage has prompted research aimed at assessing the role of anti-HLA antibody
      (Ab) monitoring as a tool to predict allograft outcome. Data on the natural
      history of allografts in children developing de novo Ab after transplantation are
      limited. Utilizing sera collected pretransplant, and serially posttransplant, we
      retrospectively evaluated 82 consecutive primary pediatric kidney recipients,
      without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence,
      and compared results with clinical-pathologic data. At 4.3-year follow up, 19
      patients (23%) developed de novo DSA whereas 24 had de novo non-DSA (NDSA, 29%).
      DSA appeared at a median time of 24 months after transplantation and were mostly
      directed to HLA-DQ antigens. Among the 82 patients, eight developed late/chronic
      active C4d+ antibody-mediated rejection (AMR), and four C4d-negative AMR. Late
      AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1-year
      median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at
      follow up, significantly higher than NDSA and Ab-negative patients (p < 0.005).
      In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR
      and graft loss; treatment started at Ab emergence might prevent AMR occurrence
      and/or progression to graft failure.

PMID- 22959075
TI  - Developmental timing of first drug treatment and 10-year patterns of drug use.
AB  - To examine the developmental timing of first drug treatment and its associations
      with 10-year drug use patterns, pooled data (N=1318) from four longitudinal
      studies conducted in California was used to compare individuals first treated
      during young adulthood (26%) to those first treated at an older age. Treatment
      timing was associated with particular participant characteristics and
      experiences. Matched data showed that most people in both age groups exhibited a
      low level of drug use after first treatment, albeit fewer who were first treated
      during young adulthood maintained a low drug use level over time. Receipt of more
      drug treatment over 10 years was associated with maintenance of low drug use
      levels among those first treated as young adults, but not among those first
      treated as older adults. Developmental timing of first drug treatment interacts
      with subsequent treatment experiences in ways that impact the course of drug use.

PMID- 22959076
TI  - Circuitry and dynamics of human transcription factor regulatory networks.
AB  - The combinatorial cross-regulation of hundreds of sequence-specific transcription
      factors (TFs) defines a regulatory network that underlies cellular identity and
      function. Here we use genome-wide maps of in vivo DNaseI footprints to assemble
      an extensive core human regulatory network comprising connections among 475
      sequence-specific TFs and to analyze the dynamics of these connections across 41
      diverse cell and tissue types. We find that human TF networks are highly cell
      selective and are driven by cohorts of factors that include regulators with
      previously unrecognized roles in control of cellular identity. Moreover, we
      identify many widely expressed factors that impact transcriptional regulatory
      networks in a cell-selective manner. Strikingly, in spite of their inherent
      diversity, all cell-type regulatory networks independently converge on a common
      architecture that closely resembles the topology of living neuronal networks.
      Together, our results provide an extensive description of the circuitry,
      dynamics, and organizing principles of the human TF regulatory network.

PMID- 22959077
TI  - [Financial evaluation in the health field].

PMID- 22959079
TI  - [Malignant myoepithelial breast carcinoma: diagnosis and therapeutic
      difficulties].
AB  - Myoepithelial carcinoma of the breast is a rare and malignant tumor. Local
      recurrence and distant metastasis are common. Treatment is not consensual. Here,
      we report a case of a 61-year-old female who developed a myoepithelial carcinoma.
      Primary treatment was a local wide excision with clear pathological margins.
      Three years later, a local recurrence was treated by further wide excision.
      Neither recurrences nor distant metastasis were detected four years later.
      Regular following of patients with myoepithelial carcinoma is essential.

PMID- 22959080
TI  - [How I do... laparoscopic repair of vaginal vault prolapse by lateral
      suspension].

PMID- 22959081
TI  - [How I do... ultrasound in the diagnosis of fetal head engagement].

PMID- 22959082
TI  - [Systematic umbilical cord blood analysis at birth: feasibility and reliability
      in a French labour ward].
AB  - OBJECTIVES: At birth, evaluation of neonatal well-being is crucial. It is though
      important to perform umbilical cord blood gas analysis, and then to analyze the
      samples. We wanted to establish the feasibility and reliability of systematic
      umbilical cord blood sampling in a French labour ward. PATIENTS AND METHODS:
      Study of systematic umbilical cord blood gas analysis was realized
      retrospectively from 1000 consecutive deliveries. We first established the
      feasibility of the samples. Feasibility was defined by the ratio of complete cord
      acid-base data on the number of deliveries from alive newborns. Afterwards, we
      established the reliability on the remaining cord samples. Reliability was the
      ratio of samples that fulfilled quality criteria defined by Westgate et al. and
      revised by Kro et al., on the number of complete samples from alive newborns. At
      last, we looked for factors that would influence these results. RESULTS: The
      systematic umbilical cord blood sample feasibility reached 91.6%, and the
      reliability reached 80.7%. About the delivery mode, 38.6% of emergency caesarians
      (IC 95% [30.8-46.3]; P<0.0001) led to non-valid samples, when only 11.3% of
      programmed caesarians (IC 95% [4.3-18.2]; P<0.0001) led to non-valid samples.
      Umbilical cord blood analysis were significantly less validated during emergency
      caesarians. DISCUSSION AND CONCLUSION: Realization of systematic cord blood gas
      analysis was followed by 8.4% of incomplete samples, and by 19.3% that were
      uninterpretable. Training sessions should be organized to improve the feasibility
      and reliability, especially during emergency caesarians.

PMID- 22959083
TI  - [How I do... ethanol sclerotherapy for ovarian endometriomas].

PMID- 22959084
TI  - Experience of place for young adults under 65 years with complex disabilities
      moving into purpose-built residential care.
AB  - The aim of this research was to examine first-person accounts of the significance
      of place for young adults (aged between 18 and 65 years of age) with complex
      disabilities moving into purpose-built residential care accommodation. Interviews
      with residents, family members and staff working at the accommodation site
      considered the impact of the physical, care and social environment on the
      experience of place. Five elements of experience were identified, including (a)
      freedom and self-expression, (b) designed for disability (c) flexible and
      responsive care environment, (d) establishing relationships and (e) defining
      spaces. Findings confirmed the need for a 'value added approach' to housing and
      support for young adults with complex disability. A value added approach extends
      the importance of place beyond the physical context for people with complex
      conditions and incorporates essential symbolic and relational concepts of value-
      being of value (for family members), having value (for residents) and giving
      value (for staff). The framework of the therapeutic landscape is applied within
      the context of supported residential care and the factors that promote a healing
      environment are examined.

PMID- 22959078
TI  - TGF-beta family signaling in stem cells.
AB  - BACKGROUND: The diversity of cell types and tissue types that originate
      throughout development derives from the differentiation potential of embryonic
      stem cells and somatic stem cells. While the former are pluripotent, and thus can
      give rise to a full differentiation spectrum, the latter have limited
      differentiation potential but drive tissue remodeling. Additionally cancer
      tissues also have a small population of self-renewing cells with stem cell
      properties. These cancer stem cells may arise through dedifferentiation from non
      stem cells in cancer tissues, illustrating their plasticity, and may greatly
      contribute to the resistance of cancers to chemotherapies. SCOPE OF REVIEW: The
      capacity of the different types of stem cells for self-renewal, the establishment
      and maintenance of their differentiation potential, and the selection of
      differentiation programs are greatly defined by the interplay of signaling
      molecules provided by both the stem cells themselves, and their microenvironment,
      the niche. Here we discuss common and divergent roles of TGF-beta family
      signaling in the regulation of embryonic, reprogrammed pluripotent, somatic, and
      cancer stem cells. MAJOR CONCLUSIONS: Increasing evidence highlights the
      similarities between responses of normal and cancer stem cells to signaling
      molecules, provided or activated by their microenvironment. While TGF-beta family
      signaling regulates stemness of normal and cancer stem cells, its effects are
      diverse and depend on the cell types and physiological state of the cells.
      GENERAL SIGNIFICANCE: Further mechanistic studies will provide a better
      understanding of the roles of TGF-beta family signaling in the regulation of stem
      cells. These basic studies may lead to the development of a new therapeutic or
      prognostic strategies for the treatment of cancers. This article is part of a
      Special Issue entitled Biochemistry of Stem Cells.

PMID- 22959092
TI  - Synchronous perianal metastasis of lung adenocarcinoma: report of a case.

PMID- 22959093
TI  - Hepatitis C virus and lipids in the era of direct acting antivirals (DAAs).
AB  - The six different HCV-genotypes have marked differences in response to therapy
      with pegylated interferon-alpha and ribavirin. The introduction of the direct
      acting antiviral (DAA) protease inhibitors, telaprevir and boceprevir in
      combination with pegylated interferon-alpha and ribavirin has become the new
      standard of care for genotype 1 infection. Several host factors associated with
      response to pegylated interferon-alpha and ribavirin are not as important in
      predicting response to triple therapy, and yet low-density lipoprotein
      cholesterol (LDLC) and statin use remain important associations of outcome with
      DAAs. This review focuses on the clinical associations between lipids and
      treatment response to interferon based antiviral treatments. We consider how
      understanding the interactions of HCV and host lipid metabolism remains relevant
      in the era of DAAs for genotype 1 infection and for treatment of non-genotype 1
      chronic hepatitis C.

PMID- 22959094
TI  - Intragastric acidity during the first day following administration of low-dose
      proton pump inhibitors: a randomized crossover study.
AB  - OBJECTIVE: Low-dose proton pump inhibitors (PPIs) are often administrated as
      maintenance therapy for gastroesophageal reflux disease (GERD) and on-demand PPI
      therapy is a viable option for long-term management of GERD. The aim of this
      study is to investigate intragastric acidity during the first day following the
      administration of low-dose PPIs. SUBJECTS AND METHODS: The study employed a
      crossover design. The subjects were 10 healthy volunteers who were administrated
      lansoprazole 15 mg (orally disintegrating) or rabeprazole 10mg. All subjects
      underwent pH monitoring with a wireless system during the first day after PPI
      administration. RESULTS: There was no significant difference in the average
      intragastric pH during the first day of administration of lansoprazole and
      rabeprazole (3.3+/-1.1 vs. 3.2+/-0.7, paired t test), although the pH was
      significantly higher with both drugs as compared with the baseline (1.8+/-0.4,
      P<0.01). The pH 4 holding time ratio during the first day showed no significant
      difference between lansoprazole and rabeprazole (35.2+/-22.4% vs. 34.3+/-15.0%),
      and was also significantly higher than at baseline (0.35+/-1.73%, P<0.01). The
      two PPIs differed with respect to the peak of the pH 4 holding time ratio.
      CONCLUSIONS: Lansoprazole 15 mg and rabeprazole 10 mg showed sufficient
      inhibition of intragastric acidity during the first day after PPI administration
      and the effects did not differ between drugs, although there was a difference in
      their time at which the peak effects were reached.

PMID- 22959095
TI  - MELD-based graft allocation system fails to improve liver transplantation
      efficacy in a single-center intent-to-treat analysis.
AB  - BACKGROUND: Since March 2007, priority access to liver transplantation in France
      has been given to patients with the highest MELD scores. OBJECTIVE: To undertake
      an intent-to-treat comparison of center-based vs. MELD-based liver graft
      allocation. METHODS: Retrospective cohort analysis (patients listed 6th March
      2007 to 5th March 2009; MELD period) with a matched historical cohort (patients
      listed 6th March 2005 to 5th March 2007; pre-MELD period) in a single high-volume
      center. Analysis was on an intent-to-treat basis, i.e. starting on the day of
      wait listing. RESULTS: Compared to pre-MELD, fewer patients with a MELD score
      less or equal to 14 (P=0.002), and more patients with a MELD greater or equal to
      24 (P<0.05) were transplanted during the MELD period. For HCC candidates, median
      waiting time increased (121 vs. 54 days, P=0.01), transplantation rate halved
      (35% vs. 73.5%, P<0.001) and dropouts due to tumor progression increased (16% vs.
      0%, P<0.001). Moreover, postoperative course did not change significantly except
      for infectious complications (35% vs. 24%, P=0.02); overall patient survival was
      69.8 +/- 3.1% vs. 76 +/- 2.9% (P=0.29) and overall graft survival was 77.6 +/-
      3.4% vs. 82.8 +/- 2.9% (P=0.29). Transplant failures were mainly due to deaths on
      the waiting list in the previous system, but to dropouts related to disease
      progression in the new system. Cirrhotic patient survival rate did not change
      (78.1 +/- 4.4% vs. 73.5 +/- 4.5%, P=0.42), while that of HCC patients decreased
      (65.3 +/- 5.3% vs. 86.8 +/- 4.4%, P=0.01). Post-transplant survival worsened
      significantly according to pre-transplant MELD score (P=0.009). CONCLUSION: The
      MELD-based graft allocation system introduced discrimination against HCC
      patients, whose incidence has increased dramatically, and should be reevaluated.

PMID- 22959097
TI  - Blackberry pigment (whitlockite) gallstones in uremic patient.
AB  - Black pigment gallstones represent nearly the 15% of all gallstones and are
      usually related with the typical "hyperbilirubinbilia" factors as hemolysis,
      ineffective erythropoiesis, pathologic enterohepatic cycling of unconjugated
      bilirubin, cirrhosis and with gallbladder mucosa (parietal) factors as
      adenomyomatosis. During a prospective study on 179 patients who underwent
      cholecystectomy for gallstone disease a 69-year-old female with predialysis
      chronic kidney disease was operated for symptomatic gallstone. The removed
      gallstones were black pigment gallstones, with an irregular (as small blackberry)
      surface. Analysis of the stones revealed a great amount of whitlockite (Ca Mg)3
      (PO4)2. Recent studies on chronic renal failure patients found that chronic
      uremia is associated with an increased risk of gallstones formation (22%) as it
      seems in women affected by primary hyperparathyroidism (30%). The presence of
      calcium phosphate gallstones in these patients have been never described. In
      conclusion, further studies could be necessary to establish the role of chronic
      renal failure and of primary and secondary hyperparathyroidism in gallstones
      formation and, in particular, if dialysis and predialysis patients have an higher
      risk to develop cholesterol and black pigment gallstones in particular of the
      "blackberry" (whitlockite) subtype.

PMID- 22959098
TI  - Performances of Elasto-FibroTest((r)), a combination between FibroTest((r)) and
      liver stiffness measurements for assessing the stage of liver fibrosis in
      patients with chronic hepatitis C.
AB  - BACKGROUND: FibroTest((r)) (FT), and liver stiffness measurement (LSM) are the
      most validated techniques for the non-invasive assessment of fibrosis in patients
      with chronic hepatitis C (CHC). The combination between FibroTest((r)) and LSM
      has never been assessed using methods assuming that biopsy is not a perfect gold
      standard. AIM: The aim was to assess the performance of a new test the Elasto
      FibroTest((r)) (EFT) combining FibroTest((r)) and LSM. METHODS: An integrated
      data base of 1289 patients with biopsy and 604 healthy volunteers was analyzed.
      EFT took into account the applicability of both tests, included two algorithms
      taking one for the diagnosis of advanced fibrosis (EFT-F2) and one for the
      diagnosis of cirrhosis (EFT-F4). Performances of EFTs were assessed by three
      methods: area under the ROC curve (AUROC), "Obuchowski method" (OBU) and 1 TAGS
      the "Latent class with random factor". RESULTS: For the diagnosis of advanced
      fibrosis EFT-F2 performances (specificity=0.99 and sensitivity=0.83) were not
      greater than the performances of FibroTest((r)) alone (specificity=0.93 and
      sensitivity=0.99). For the diagnosis of cirrhosis, EFT-F4 performances were
      greater than those of FibroTest((r)) alone, particularly for the sensitivity
      (0.88 vs. 0.74); when compared with LSM, EFT-F4 performances (specificity=0.99
      and sensitivity=0.99) were also greater than those of LSM alone particularly
      because of its lower specificity (0.92). CONCLUSION: For the diagnosis of
      cirrhosis the Elasto-FibroTest((r)) has higher performances than FibroTest((r))
      or FibroScan((r)) alone. No improvement in performance has been observed for the
      diagnosis of advanced fibrosis vs. FibroTest((r)) alone.

PMID- 22959099
TI  - Hepatitis B virus and hepatitis C virus co-infection: a therapeutic challenge.
AB  - Hepatitis B virus and hepatitis C virus are the two most common causes of chronic
      liver disease in the world. Dual infection with hepatitis B virus and hepatitis C
      virus, whose prevalence is underestimated, is characterized by a more severe
      liver injury, a higher probability of liver cirrhosis and a higher incidence of
      hepatocellular carcinoma. Treatment of these patients represents a therapeutic
      challenge. We report the case of an hepatitis B virus-hepatitis C virus co
      infected patient, which particularly illustrates the interactions between these
      two viruses and therapeutic problems caused by the dual infection. HCV was
      initially dominant, which indicated a combination therapy by pegylated interferon
      and ribavirin. This treatment was associated with an early virological response
      of the HCV but an increase of HBV DNA occurred, requiring the use of a nucleoside
      analogue. A good response was obtained for the HBV but a relapse of HCV was
      noted, posing a problem for therapeutic decision.

PMID- 22959100
TI  - Treatment outcomes according to endoscopic treatment modalities for rectal
      carcinoid tumors.
AB  - BACKGROUND: Despite a growing understanding of the clinical effectiveness of
      endoscopic treatment for small rectal carcinoid tumors, there is still
      controversy concerning the best endoscopic treatment for resecting rectal
      carcinoid tumors easily and effectively. OBJECTIVES: The objective of the present
      study was to compare the therapeutic efficacy and safety of endoscopic submucosal
      resection with a ligation device (ESMR-L) with endoscopic submucosal dissection
      (ESD) for rectal carcinoid tumors. In addition, a conventional snare-based
      endoscopic mucosal resection (EMR) was included in the study and compared with
      both ESMR-L and ESD. METHODS: A retrospective analysis was performed in 115
      patients who underwent endoscopic resection of a rectal carcinoid tumor between
      January 2005 and June 2011. These patients were classified into three groups
      according to the type of endoscopic procedure: EMR group (n=33), ESMR-L group
      (n=40) and ESD group (n=44). RESULTS: The complete resection rate of the EMR
      group was significantly lower than those of the ESMR-L and ESD groups (77.4 vs.
      100 and 97.7%, P=0.002 and P=0.007). Tumor-free vertical margins were
      significantly greater in the ESMR-L and ESD groups than in the EMR group (ESMR-L
      and ESD vs. EMR group, P=0.013 and P=0.041). The curative resection rate of
      rectal carcinoid tumors in the EMR group was 77.4%, which was significantly lower
      than that of the ESMR-L (95%, 38/40) and EDS groups (97.7%, 43/44) (77.4% vs.
      95%, P=0.036 and 77.4% vs. 97.7%, P=0.007). CONCLUSIONS: Our results show that
      ESMR-L and ESD might be superior to conventional EMR for the treatment of small
      rectal carcinoid tumors.

PMID- 22959101
TI  - Autoantibodies in autoimmune hepatitis: anti-asialoglycoprotein receptor (anti
      ASGPR) antibodies.

PMID- 22959102
TI  - The Spanish version of the Addenbrooke's Cognitive Examination - Revised (ACE-R)
      in subcortical ischemic vascular dementia.
AB  - Vascular dementia (VaD) is one of the most prevalent causes of dementia, and it
      is frequently misdiagnosed and undertreated in clinical practice. Because
      neuropsychological outcome depends, among other factors, on the size and location
      of the vascular brain injury, characterizing the cognitive profile of VaD has
      been especially challenging. Yet, there has been sufficient evidence to show a
      marked impairment of attention and executive functions, in particular in relation
      to Alzheimer disease. Being able to detect these deficits at bedside is crucial
      for everyday clinical practice, and yet, brief cognitive screening toots such as
      the Mini-Mental Sate Examination (MMSE) may overlook at cognitive deficits
      typical of patients with VaD. The Addenbrooke's Cognitive Examination Revised
      (ACE-R) is also a brief cognitive screening tool designed to incorporate the
      items of the MMSE and further extend the test to assess orientation, attention,
      verbal fluency, memory, language, and visuospatial abilities. In this study, we
      investigated the ability of the Spanish version of the ACE-R to detect the
      cognitive impairment showed in patients with subcortical ischemic vascular
      dementia, and we compared its usefulness to that of the MMSE in this population.
      Scores on these tests were compared to those of patients with Alzheimer disease
      and matched healthy controls. The 88-point cut-off proposed for the ACE-R was
      associated with a sensitivity of 100% and a specificity of 100% for the detection
      of cognitive impairment, demonstrating a stronger capacity than the MMSE
      (sensitivity of 42% with its 23-point cut-off score). We also found that the
      verbal fluency subtest of the ACE-R may be potentially useful in discriminating
      patients with subcortical ischemic vascular dementia from patients with AD. We
      discuss the utility of these findings in the context of everyday clinical
      practice and we propose that future studies should evaluate the potential
      usefulness of combining the ACE-R with a brief screening tool of executive
      functioning.

PMID- 22959103
TI  - Factors promoting success and influencing complications in laser-induced central
      vein bypass.
AB  - PURPOSE: To evaluate the factors influencing the successful creation of a laser
      induced chorioretinal venous anastomosis (L-CRA) and those involved in the
      development of complications. DESIGN: Interventional cohort study. PARTICIPANTS:
      Fifty-five patients with a nonischemic central retinal vein occlusion (CRVO) who
      were randomized to receive an L-CRA from the total of 108 who completed the
      follow-up period of the Central Vein Bypass Study. METHODS: Patients who were
      randomized to L-CRA were followed up for an 18-month period. They were stratified
      in 2 sets of 2 cohorts: those who did or did not demonstrate an L-CRA and those
      who did or did not demonstrate neovascular complications at the site of the L
      CRA. Subgroup analysis was performed to determine what factors influenced the
      creation of an L-CRA and the development of complications at each individual
      laser site. MAIN OUTCOME MEASURES: Identification of systemic and local ocular
      factors associated with increased success rates of L-CRA creation and those
      involved with an increased risk of neovascular complications. RESULTS: Younger
      age (P = 0.03), better baseline visual acuity (P = 0.04), and the absence of
      hypertension (P = 0.001) were systemic features associated with an increased
      chance of demonstrating a successful L-CRA at each site, whereas sex and duration
      of the CRVO were not. The position of the L-CRA site did not influence the
      outcome; however, evidence of rupture of the vein wall at the time of the attempt
      was associated with a higher chance of success (P = 0.008). Increased risk of
      neovascularization, which occurred at 12 sites in 10 eyes, was associated with
      higher central venous pressure before treatment (P = 0.03), prolonged fluorescein
      transit time (P = 0.0001), and the presence of some capillary nonperfusion (P =
      0.01). CONCLUSIONS: Younger age, better baseline visual acuity, and the absence
      of hypertension were associated with an improved success rate, as was evidence of
      rupture of the vein wall. High baseline central venous pressure, prolonged
      fluorescein transit time, and the presence of any retinal ischemia were
      associated with a higher incidence of neovascular complications. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 22959104
TI  - Risk of age-related macular degeneration 3 years after cataract surgery: paired
      eye comparisons.
AB  - OBJECTIVE: To clarify possible associations between cataract surgery and
      progression of age-related macular degeneration (AMD). DESIGN: Clinic-based
      cohort. PARTICIPANTS: We followed cataract surgical patients aged 65+ years in
      the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD)
      study. Patients who remained unilaterally phakic for at least 24 months after
      recruitment were included. METHODS: We performed annual examinations with retinal
      photography. We assessed AMD using side-by-side grading of images from all
      visits. Paired comparisons between operated and nonoperated fellow eyes (defined
      as nonoperated or operated <12 months previously) were made using generalized
      estimating equation models. MAIN OUTCOME MEASURES: Incident early AMD was defined
      as the new appearance of soft indistinct/reticular drusen or coexisting retinal
      pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD.
      Incident late AMD was defined as the new appearance of neovascular AMD or
      geographic atrophy (GA) in eyes at risk of late AMD. RESULTS: Among 2029
      recruited, eligible participants, 1851 had cataract surgery performed at Westmead
      Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these
      participants, 1178 had gradable photographs at baseline and at least 1 follow-up
      visit. Of 308 unilaterally operated participants at risk of late AMD, this
      developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio
      [OR], 0.74; 95% confidence interval [CI], 0.23-2.36) after adjusting for the
      presence of early AMD at baseline. Of 217 unilaterally operated participants at
      risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%)
      nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74-1.65). Incident retinal pigment
      abnormalities were more frequent in operated than nonoperated fellow eyes (15.3%
      vs. 9.9%; OR, 1.64; 95% CI, 1.07-2.52). There was no difference in the 3-year
      incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8%
      vs. 7.9%; OR, 1.12; 95% CI, 0.79-1.60). CONCLUSIONS: Prospective follow-up data
      and paired eye comparisons of this older surgical cohort showed no increased risk
      of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There
      was a 60% increased detection of retinal pigmentary changes in surgical eyes.

PMID- 22959105
TI  - Anterior segment optical coherence tomography in congenital corneal opacities.
AB  - PURPOSE: To evaluate the clinical usefulness of anterior segment (AS) optical
      coherence tomography (OCT) in diagnosis and follow-up of children with congenital
      corneal opacities. DESIGN: Noncomparative case series. PARTICIPANTS: Seven
      consecutive patients with bilateral congenital corneal opacity between 2 days and
      2.5 years of age. METHODS: In addition to basic outpatient examination, eyes were
      imaged using AS OCT. Anterior segment structures and corneal thicknesses were
      evaluated from the images. Three children also underwent evaluation under
      anesthesia, including measurement of corneal thickness with ultrasound
      pachymetry. MAIN OUTCOME MEASURES: Evaluation of the type and severity of the
      congenital corneal opacity based on the findings in AS OCT. RESULTS: Thirteen of
      the 14 eyes could be imaged using AS OCT. The youngest patient studied was only 2
      days old. Three distinct phenotypes were found based on the AS OCT findings.
      Three patients with iridocorneal adhesions were deduced to have type 1 Peters'
      anomaly, and 2 patients with lenticulocorneal adhesions were deduced to have type
      2 Peters' anomaly. The 2 youngest patients had complete corneal opacity with
      features of corneal staphyloma and marked changes in the AS structures during the
      first months of life. CONCLUSIONS: Anterior segment OCT was a valuable method in
      the diagnosis and follow-up of patients with congenital corneal opacities. As a
      fast and noncontact technique, it was applicable even for neonates. It allowed
      early characterization of the type and the extent of the AS disorder. FINANCIAL
      DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any
      materials discussed in this article.

PMID- 22959106
TI  - Free floating left atrial ball thrombus: a rare cause of stroke.
AB  - In the setting of mitral valve stenosis and atrial fibrillation, left atrial ball
      thrombus is a rare but recognized cause of stroke and can occur even in the
      presence of therapeutic anticoagulation. This case report highlights the need for
      echocardiography to rule out treatable cardioembolic substrates for stroke. We
      report a case of cardioembolic stroke as a result of free floating left atrial
      ball thrombus presenting as a complication of rheumatic mitral valve disease.
      This case highlights that, in all patients with a history of structural heart
      disease, atrial fibrillation, or rheumatic fever, prompt cardiac ultrasound to
      exclude free floating atrial thrombus is essential. 

PMID- 22959107
TI  - Relative changes in transcranial Doppler velocities are inferior to absolute
      thresholds in prediction of symptomatic vasospasm after subarachnoid hemorrhage.
AB  - The absolute transcranial Doppler (TCD) velocity threshold has been validated as
      a screening tool for vasospasm after subarchnoid hemorrhage (SAH). We assessed
      whether relative changes in velocity were superior to absolute TCD thresholds in
      the detection of symptomatic vasospasm. We reviewed consecutive patients with
      aneurysmal SAH who underwent serial TCD monitoring and survived at least 7 days.
      We recorded initial flow velocity (IFV) and maximal flow velocity (MFV) of the
      middle cerebral artery (MCA) serially up to 14 days from admission. We calculated
      relative flow velocity changes (MFV/IFV) and maximum change in mean flow velocity
      (FVmean) over any consecutive 2 days in addition to standard absolute measures of
      Lindegaard ratio (LR) and FVmean. We calculated receiver operating characteristic
      curve and area under curve (AUC) values, sensitivity, specificity, and positive
      predictive and negative predictive values for these parameters, optimal
      cutpoints, and various combinations. Forty-eight of 211 patients (23%) developed
      symptomatic MCA vasospasm. AUC values for various TCD parameters were 0.80 for
      MCA MFV >175 cm/s, 0.71 for LR >6, 0.64 for MFV/IFV >2, and 0.64 for >70% change
      in MFV over 2 days. The best characteristics were observed for the combination of
      MFV >175 cm/s and/or maximal LR >6 (AUC 0.81). Our data suggest that absolute
      thresholds of TCD FVmean provide the most accurate prediction of symptomatic MCA
      vasospasm after SAH. Other thresholds, including relative change from baseline
      and day-to-day changes, are inferior to established absolute thresholds. 

PMID- 22959108
TI  - Cerebral infarction in both carotid and vertebrobasilar territories associated
      with a persistent primitive hypoglossal artery with severe dilated
      cardiomyopathy.
AB  - A persistent primitive hypoglossal artery (PPHA) is a relatively rare vascular
      anomaly of a persistent carotid-basilar anastomosis. A 76-year-old man with
      severe dilated cardiomyopathy suddenly lost consciousness. A magnetic resonance
      imaging scan of his brain revealed extensive infarction in the carotid and
      vertebrobasilar territories. Magnetic resonance angiography revealed a PPHA and
      occlusion of the left internal carotid artery and vertebrobasilar artery.
      Cardioembolic infarction associated with a PPHA should be recognized as a
      possible cause of multiple infarctions in both the carotid and vertebrobasilar
      distributions in the absence of stenotic ICA lesions. 

PMID- 22959109
TI  - Antithrombotic drug uses and deep intracerebral hemorrhages in stroke patients
      with deep cerebral microbleeds.
AB  - BACKGROUND: It has been suggested that antiplatelet or anticoagulant drugs
      elevate the rate of intracerebral hemorrhage (ICH) in patients with cerebral
      microbleeds (MBs). To investigate the mechanism by which antiplatelet drugs or
      warfarin may contribute to deep ICH occurrences in patients with deep MBs, we
      prospectively analyzed deep ICH occurrences in 807 consecutive patients (351
      females and 456 males; mean age +/- standard deviation 69.8 +/- 12.0 years) who
      were admitted to our hospital with strokes. METHODS: Occurrence-free rate curves
      were generated using the Kaplan-Meier method; deep ICH occurrence-free rates were
      compared using the log-rank test. The follow-up period was 0.5 to 71 months (mean
      +/- standard deviation 31.6 +/- 22.2 months). RESULTS: In patients with deep MBs,
      the rates (1.0%/year; 6 ICHs in 180 patients) of deep ICH occurrence associated
      with antiplatelet drugs were not significantly greater than that without the
      drugs (1.0%/year; 6 ICHs in 167 patients; P = .977). The incidence of deep ICHs
      associated with warfarin use was not significantly greater than that without
      warfarin use. CONCLUSIONS: Multivariate analysis revealed that the use of
      antiplatelet drugs or warfarin did not significantly influence the occurrence of
      deep ICH in patients with deep MBs. Antiplatelet drugs or warfarin did not
      significantly elevate the rate of deep ICHs in stroke patients with pre-existing
      deep MBs.

PMID- 22959111
TI  - A new chapter in the history of depression.

PMID- 22959110
TI  - Phase I study of intravenous low-dose granulocyte colony-stimulating factor in
      acute and subacute ischemic stroke.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be
      useful for the treatment of acute ischemic stroke because of its neuroprotective
      and neurogenesis-promoting properties, but an excessive increase of neutrophils
      may lead to brain injury. We examined the safety and tolerability of low-dose G
      CSF and investigated the effectiveness of G-CSF given intravenously in the acute
      phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke. METHODS:
      Three intravenous dose regimens (150, 300, or 450 MUg/body/day, divided into 2
      doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance
      imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery.
      Nine patients received the first dose at 24 hours poststroke (acute group) and 9
      patients received the first dose on day 7 poststroke (subacute group; n = 3 at
      each dose in each group). A scheduled administration of G-CSF was skipped if the
      patient's leukocyte count exceeded 40,000/MUL. Patients received neurologic and
      MRI examinations. RESULTS: We found neither serious adverse event, drug-related
      platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/MUL
      at 150 and 300 MUg G-CSF/body/day, but rose above 40,000/MUL at 450 MUg G
      CSF/body/day. Neurologic function improvement between baseline and day 90 was
      more marked after treatment in the acute phase versus the subacute phase (Barthel
      index 49.4 +/- 28.1 v 15.0 +/- 22.0; P < .01). CONCLUSIONS: Low-dose G-CSF (150
      and 300 MUg/body/day) was safe and well tolerated in ischemic stroke patients,
      and leukocyte levels remained below 40,000/MUL.

PMID- 22959112
TI  - Circadian dimension and severity of depression.
AB  - The cyclic nature of depressive illness, disturbance of diurnal mood variations,
      and disturbed sleep-wake and physiological rhythms all suggest that dysfunction
      of the circadian time-keeping system may underlie the pathophysiology of
      depression. Circadian misalignment of the phase-delayed type appears to be the
      most common shift in unipolar disorder patients and misalignment between the
      timing of sleep and the pacemaker is correlated with depressive symptom severity.
      Profiles of diurnal mood variation are associated with risks of depression
      severity and may predict response to treatments. As circadian disturbances are at
      the core of depression, normalizing circadian rhythm may be a fruitful avenue for
      new therapeutic targets in depression. The innovative antidepressant agomelatine
      possesses resynchronizing properties that may be related to its original profile
      and offers an opportunity to achieve our goals in treating depressed people.

PMID- 22959113
TI  - Neural correlates of emotion processing: from emotional to social brain.
AB  - Different models of emotion highlight the role of strategic brain regions in
      emotion identification, response and regulation. Cortical, subcortical and limbic
      structures constitute the emotional brain. In this short review, we focus on the
      function of the amygdala and medial prefrontal cortex. Both regions have
      reciprocal connections and are densely connected with cortical and subcortical
      structures. Beyond its classical role in fear processing, the amygdala is
      considered as a region that detects salient and personally relevant stimuli in
      cooperation with ventral and dorsal medial prefrontal cortex. Amygdala and medial
      prefrontal cortex are also engaged in the processing of socially relevant
      stimuli. Our review emphasized the overlap between the emotional and the social
      brain. Adopting a socio-affective neuroscience perspective is a promising
      perspective to identify new pathophysiological pathways in the study of emotion
      and mental disorders, especially major depressive disorder.

PMID- 22959114
TI  - Onset, time course and trajectories of improvement with antidepressants.
AB  - There is still considerable controversy about the onset and time course of
      improvement with antidepressants in the treatment of major depressive disorder.
      Previous studies suggested a delayed-onset hypothesis with therapeutic
      improvement taking several weeks, but recent meta-analyses have shown support for
      earlier onset of improvement within the first week or two of treatment. This
      paper briefly reviews the evidence, focused on antidepressant studies published
      since 2006, for early onset of improvement within the first 2 weeks of treatment.
      A PubMed electronic search was conducted with selection of relevant studies from
      2007 to March 2012. With the caveat of methodological limitations, results from
      randomized clinical trials, meta-analyses and naturalistic studies consistently
      show that: (1) antidepressants in general have early onset of improvement, (2)
      some antidepressants, including the novel mechanism agent, agomelatine, are
      associated with early improvement in both core and specific symptoms such as
      anhedonia and sleep-wake disturbances, and (3) early improvement predicts
      sustained response and remission. Use of newer statistical methods to examine
      individual response trajectories may address some of the methodological
      limitations of previous studies. The predictive value of early improvement has
      important clinical relevance for antidepressant treatment. Measurement-based
      assessment for response should occur earlier and more frequently. A lack of
      improvement (defined as <=20% reduction from baseline in scores on a depression
      rating scale) at 2-3 weeks after initiation of an antidepressant should prompt
      the clinician to consider a change in management.

PMID- 22959115
TI  - The relation between mood, cognition and psychosocial functioning in psychiatric
      disorders.
AB  - Impairments in cognitive performance and inability to function in everyday life
      situations are present, in various degrees, in many severe mental illnesses,
      including major depressive disorder, bipolar disorder, and schizophrenia.
      Persistent mood symptoms (e.g., depression and mania) are associated with
      functional deficits in major depression and bipolar disorder, but also in
      conditions where mood symptoms are not the primary markers of the illness, such
      as in schizophrenia. While mood symptoms impact cognitive performance, both mood
      symptoms and cognitive deficits have a significant - and to some extent
      independent - impact on psychosocial functioning in psychiatric patients.
      Improved control of mood symptoms may represent an important strategy leading to
      improved functional outcomes. However, cognitive impairment may be an important
      independent dimension of many psychiatric disorders and such symptoms should also
      be considered a potential target of treatments aiming to reduce functional
      deficits.

PMID- 22959116
TI  - Anhedonia and major depression: the role of agomelatine.
AB  - Anhedonia is a condition in which the capacity to experience pleasure is totally
      or partially lost. Although anhedonia is a feature of major depressive disorder
      according to DSM IV criteria for major depression diagnosis, so far it has
      received relatively little attention. The scale that is most commonly used in the
      measurement of anhedonia is the Snaith-Hamilton Pleasure Scale (SHAPS), a brief
      14-item self-report questionnaire designed to measure hedonic tone and its
      absence. Two studies have described the efficacy of agomelatine in the treatment
      of anhedonia: an open-label study and a comparative trial versus the
      antidepressant venlafaxine XR. In both studies agomelatine significantly reduced
      anhedonia, as indicated using the SHAPS. This reduction was observed after the
      first week of treatment (P<0.05) and at different times until the end of the
      trial. Moreover, in the comparative trial, a significant difference between
      groups was observed in favor of agomelatine, after 1 (P<0.05), 2 (P<0.01), and 8
      weeks (P<0.01). The possible effect of agomelatine on anhedonia may represent a
      novel area of interest among antidepressant agents and deserves further
      investigation, with larger samples and double-blind placebo-controlled designs.

PMID- 22959117
TI  - Injection drug users' and their risk networks' experiences of and attitudes
      towards drug dealer violence in Baltimore, Maryland.
AB  - BACKGROUND: A large portion of violence associated with drug use is due to drug
      dealing. These analyses sought to examine injection drug users' attitudes and
      experiences of drug dealer violence. METHODS: The current study used the 18-month
      follow up data of STEP into Action (STEP) study, an HIV prevention intervention
      among drug injectors and their risk network members conducted in Baltimore,
      Maryland. Four scales assessed acceptability of drug dealer violence, willingness
      to talk to drug users about avoiding drug dealer violence, social norms about
      reporting drug dealer violence and intentions to report drug dealer violence to
      the police. RESULTS: Many (44%) of the 373 participants reported witnessing drug
      dealers' acts of violence within the prior 6 months. Although the majority of
      participants disagreed with statements on the acceptability of dealers using
      violence, only a minority indicated that they would call the police if they
      observed dealer violence. Most participants indicated that they would be
      interested in talking to drug users about how to avoid violent dealers. Males
      were more likely to report that violence was acceptable, whereas African
      Americans were less likely to condone violence. Those who were homeless and had
      higher incomes were more likely to report witnessing drug dealer violence.
      CONCLUSIONS: These results suggest that it may be feasible to train current and
      former drug users and their risk network members in methods to promote violence
      reduction among drug dealers.

PMID- 22959118
TI  - Ketamine: the hopes and the hurdles.

PMID- 22959119
TI  - Evidence for global reduction in brain cyclic adenosine monophosphate signaling
      in depression.

PMID- 22959120
TI  - A "taste" of what is to come: reward sensitivity as a potential endophenotype for
      major depressive disorder.

PMID- 22959121
TI  - Renal transplant improves pulmonary hypertension in patients with end stage renal
      disease.
AB  - BACKGROUND: Pulmonary hypertension (PH) is present in a significant proportion of
      patients with end stage renal disease (ESRD) and is of prognostic importance.
      Data on the effect of renal transplant on PH is very limited. In this study, the
      aim was to examine the effect of renal transplant on systolic pulmonary artery
      pressure (SPAP) determined by Doppler echocardiography. METHODS: Analysis was
      performed on the records of 500 consecutive patients who underwent renal
      transplant at our center between the years 1999 to 2008. The prevalence of PH in
      the preoperative assessment period was established. Patients were diagnosed as
      having PH when measured SPAP values were > 35 mm Hg. RESULTS: Pulmonary
      hypertension was detected in 85 of the 500 (17%) patients under pre-transplant
      evaluation. At post-transplant follow up Doppler echocardiographic examination
      was performed on 50 of the 85 patients. After exclusion of 8 cases (1 due to
      massive pulmonary thromboemboli; 7 due to graft failure requiring dialysis
      therapy) analyses were performed on 42 patients who had undergone both pre- and
      post-transplant echocardiographic examination. Mean SPAP at pre-transplant
      evaluation was 45.9 +/- 8.8 mm Hg and in 6 (14.3%) cases SPAP was above 50 mm
      Hg.Compared to pre-transplant values, a significant decrease was observed in mean
      SPAP values in an average of 53 months of postoperative follow up (41.8 +/- 7.4
      mm Hg vs. 45.9 +/- 8.8 mm Hg, p < 0.0001). CONCLUSION: These findings indicate
      that patients with ESRD accompanied by PH may benefit from renal transplant.
      Further research is required for more concrete conclusions to be drawn on this
      subject.

PMID- 22959122
TI  - Prognostic factor for non-small cell lung cancer with bone metastases at the time
      of diagnosis.

PMID- 22959123
TI  - High-pressure macromolecular crystallography and NMR: status, achievements and
      prospects.
AB  - Biomacromolecules are thermodynamic entities that exist in general as an
      equilibrium mixture of the basic folded state and various higher-energy substates
      including all functionally relevant ones. Under physiological conditions,
      however, the higher-energy substates are usually undetectable on spectroscopy, as
      their equilibrium populations are extremely low. Hydrostatic pressure gives a
      general solution to this problem. As proteins generally have smaller partial
      molar volumes in higher-energy states than in the basic folded state, pressure
      can shift the equilibrium toward the former substantially, and allows their
      direct detection and analysis with X-ray crystallography or NMR spectroscopy at
      elevated pressures. These techniques are now mature, and their status and
      selected applications are presented with future prospects.

PMID- 22959124
TI  - [Unilateral periorbital mucinosis in systemic lupus erythematosus].

PMID- 22959125
TI  - Balancing the risks and benefits for pioglitazone in type 2 diabetes.

PMID- 22959126
TI  - Increased sensorimotor gating in recreational and dependent cocaine users is
      modulated by craving and attention-deficit/hyperactivity disorder symptoms.
AB  - BACKGROUND: Cocaine dependence has been associated with blunted dopamine and
      norepinephrine signaling, but it is unknown if recreational cocaine use is also
      associated with alterations of catecholamine systems. Prepulse inhibition (PPI)
      of the acoustic startle response-a measure of sensorimotor gating-is highly
      sensitive for manipulations of the catecholamine system. Therefore, we
      investigated whether relatively pure recreational users (RCU) and dependent
      cocaine users (DCU) display alterations of PPI, startle reactivity, and
      habituation. Moreover, the influences of methylenedioxymethamphetamine and
      cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD)
      symptoms on startle measures were examined. METHODS: In 64 RCU, 29 DCU, and 66
      stimulant-naive control subjects, PPI of acoustic startle response, startle
      reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug
      use of all participants was controlled by hair and urine toxicologies. RESULTS:
      Both RCU and DCU showed increased PPI in comparison with control participants
      (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI
      measures (d=.12). No significant group differences were found in startle
      reactivity or habituation measures. In cocaine users, PPI was positively
      correlated with cumulative cocaine dose used, craving for cocaine, and ADHD
      symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed
      the highest PPI levels compared with control subjects (d=.78). CONCLUSIONS: The
      augmented PPI in RCU and DCU suggests that recreational use of cocaine is
      associated with altered catecholamine signaling, in particular if ADHD or craving
      symptoms are present. Finally, ADHD might be a critical risk factor for cocaine
      induced changes of the catecholamine system.

PMID- 22959127
TI  - Characterization of the hypercoagulable state in patients with sickle cell
      disease.
AB  - BACKGROUND: The pathophysiology of sickle cell disease (SCD) is complex, with
      increasing evidence of a pronounced prothrombotic state. OBJECTIVE: We
      investigated thrombin generation in SCD utilizing calibrated automated
      thrombography (CAT) and D-dimer, with subsequent correlation to clinical disease.
      PATIENT/METHODS: The study included 51 patients homozygous for hemoglobin S,
      either admitted for vaso-occlusive crisis (VOC) (n=34) or while in steady state
      and being seen in outpatient clinic (n=37). Twenty patients had blood drawn
      during both VOC and steady state. Mean values for CAT and D-dimer were compared
      between groups. Mean values for patients with and without clinical complications
      such as avascular necrosis and stroke were also compared. Linear regression was
      used to evaluate correlation to number of hospitalizations and for all pediatric
      patients, transcranial doppler (TCD) velocities. RESULTS: The mean D-dimer during
      VOC (2743 +/- 3118 ng/ml) was significantly higher than during steady state (1151
      +/- 802, p<0.0001). Comparison of crisis and steady state by CAT also revealed a
      significant difference in all phases of thrombin generation, including mean
      endogenous thrombin potential (1381 +/- 295 nM vs 923 +/- 316, p<0.0001) and peak
      thrombin generated (284 +/- 9 vs 223 +/- 18, p=0.0002). There were no significant
      differences in mean values for the clinical outcomes examined in adults. In
      pediatric patients, however, increased TCD velocities correlated with steady
      state D-dimer (r(2)=0.32, p=0.02) and thrombin-antithrombin complex (r(2)=0.28,
      p=0.04. CONCLUSION: Hypercoagulable markers distinguish between patients with SCD
      during and between VOC, but do not correlate with specific clinical phenotypes.

PMID- 22959129
TI  - English proficiency and peer interethnic relations as predictors of math
      achievement among Latino and Asian immigrant students.
AB  - Studies show math achievement to be the best predictor of entering post-secondary
      education. However, less is known about the predictors of math achievement,
      particularly among immigrant youth. This study examined English proficiency and
      peer interethnic relations as predictors of mathematics achievement among Latino
      and Asian high school students, postulating an interaction between the predictors
      and mediation by academic motivation. A multilevel moderated-mediation model was
      used to analyze data from a national sample of 2113 non-native English speaking
      Latino and Asian students attending high school in the U.S. We found that higher
      academic motivation mediated the relationship between English proficiency during
      their sophomore year and gains in senior math achievement scores for both Asian
      and Latino students. For Latino students however, this indirect path was only
      significant for students whose perceptions of positive peer interethnic relations
      at school were average or above average.

PMID- 22959128
TI  - Increased risk of venous thromboembolism is associated with genetic variation in
      heme oxygenase-1 in Blacks.
AB  - BACKGROUND: Venous thromboembolism (VTE) affects as many as 1 in 1000 individuals
      in the United States. Although Blacks are disproportionately affected by VTE, few
      genetic risk factors have been identified in this population. The inducible heme
      oxygenase-1 (HMOX1) gene encodes a key cytoprotective enzyme with anti
      inflammatory, antioxidant and anticoagulant activity acting in the vascular
      system. A (GT)(n) microsatellite located in the promoter of the HMOX1 gene
      influences the level of response. METHODS AND RESULTS: Using the Genetic
      Attributes and Thrombosis Epidemiology (GATE) study, we examined the association
      between HMOX1 repeat length and VTE events in 883 Black and 927 White patients
      and matched controls. We found no association between HMOX1 genotypes and VTE in
      Whites. However, in Black patients, carrying two long (L) alleles (>= 34 repeats)
      was significantly associated with provoked (odds ratio (OR) 1.86, 95% confidence
      interval (CI): 1.19-2.90) or recurrent (OR 3.13, 95% CI: 1.77-5.53) VTE events.
      CONCLUSIONS: We have demonstrated for the first time an association between
      genetic variation in HMOX1, and VTE in Blacks. Our results support a key role for
      the heme oxygenase system in protecting patients at increased risk for thrombosis
      and suggest a potential mechanism for targeted screening and intervention.

PMID- 22959130
TI  - Aortoduodenal fistula after endograft repair of abdominal aortic aneurysm
      secondary to a retained guidewire.
AB  - Aortoduodenal fistula is a well-known complication of abdominal aortic aneurysm
      repair and has been described after endovascular repair. A unique complication of
      duodenal perforation by intentionally placed embolic material in the aneurysm sac
      is described. Intentional off-label use of material to promote aneurysm sac
      thrombosis should be avoided.

PMID- 22959131
TI  - Role of plant growth regulators and a saprobic fungus in enhancement of metal
      phytoextraction potential and stress alleviation in pearl millet.
AB  - "Assisted phytoextraction" involving application of chemical additives such as
      plant growth regulators (PGRs) has become a trend in phytoremediation technology.
      This study identifies a cost-effective, naturally available crude PGR (PGR1) that
      produces the same effects as the commercial PGR (PGR2), increasing metal uptake
      by plants and the reduction of metal stress. Assisted phytoextraction by pearl
      millet (Pennisetum glaucum) from a multi-metal (Cd, Cr, Cu, Fe, Na and Zn)
      contaminated soil medium with tannery solid waste (TSW) soil amendments of 5 and
      10%, was evaluated in a full-factorial pot trial with PGR1, PGR2 and Trichoderma
      pseudokoningii as factors. The effects of these phytoextraction assistants were
      measured through dry biomass production, heavy metal uptake, stress tolerance
      enzymes catalase (CAT) and superoxide dismutase (SOD), soluble protein content of
      plant, and phytoextraction efficiency. Dry biomass and multi-metal accumulation
      were the highest in the soil treatments with a combined application of PGR1, PGR2
      and T. pseudokoningii and the lowest in the control. The soluble protein contents
      and the SOD and CAT values were the highest in the 10% TSW treatment provided
      with PGR2+T. pseudokoningii, while the lowest were in the control. Thus,
      application of crude PGR in combination with other phytoextraction assistants can
      increase biomass production as well as multi-metal accumulation in plants.
      However, the biochemical properties of the plant depend on the level of TSW
      stress in the soil treatment as well as the type of phytoextraction assistants.

PMID- 22959132
TI  - Low-temperature loading of Cu+ species over porous metal-organic frameworks
      (MOFs) and adsorptive desulfurization with Cu+-loaded MOFs.
AB  - Porous metal-organic frameworks (MOFs, MIL-100-Fe, iron-benzenetricarboxylate)
      supported with Cu(+) species were obtained for the first time under mild
      condition without high temperature calcinations. The Cu(+)-loaded MOFs were
      evaluated as efficient adsorbents for the liquid-phase adsorption of
      benzothiophene (BT). The effect of Cu(+) loading on the adsorption kinetics and
      maximum adsorption capacity (Q(0)) for the adsorption of BT was also studied.
      Q(0) increased with increasing copper loading up to a Cu/Fe (wt./wt.) ratio of
      0.07 in Cu(+)-loaded-MIL-100-Fe, resulting in an increase in the Q(0) by 14%
      compared with the virgin MIL-100-Fe without Cu(+) ions. Since the surface area
      and pore volume decrease with the loading of copper, the increased Q(0) over the
      Cu(+)-loaded MIL-100-Fe adsorbents suggests specific favorable interactions
      (probably by pi-complexation) between Cu(+) and BT.

PMID- 22959133
TI  - Accurate prediction of the toxicity of benzoic acid compounds in mice via oral
      without using any computer codes.
AB  - Most of benzoic acid derivatives are toxic, which may cause serious public health
      and environmental problems. Two novel simple and reliable models are introduced
      for desk calculations of the toxicity of benzoic acid compounds in mice via oral
      LD(50) with more reliance on their answers as one could attach to the more
      complex outputs. They require only elemental composition and molecular fragments
      without using any computer codes. The first model is based on only the number of
      carbon and hydrogen atoms, which can be improved by several molecular fragments
      in the second model. For 57 benzoic compounds, where the computed results of
      quantitative structure-toxicity relationship (QSTR) were recently reported, the
      predicted results of two simple models of present method are more reliable than
      QSTR computations. The present simple method is also tested with further 324
      benzoic acid compounds including complex molecular structures, which confirm good
      forecasting ability of the second model.

PMID- 22959134
TI  - Concepts on charge transfer through naturally vibrating DNA molecule.
AB  - Delocalization of charges thorough DNA occurs due to the natural and continuous
      movements of molecule which stimulates the charge transfer through the molecule.
      A model is presented showing that the mechanism of electrical conduction occurs
      mainly by thermally-activated drift motion of holes under control of the
      localized carriers; where electrons are localized in the conduction band. These
      localized (stationary-trapped) electrons control the movements of the positive
      charges and do not play an effective role in the electrical conduction itself. It
      is found that the localized charge-carriers in the bands have characteristic
      relaxation times at 5*10(^-2)s, 1.94*10(^-4)s, 5*10(^-7)s, and 2*10(^-11)s
      respectively which are corresponding to four intrinsic thermal activation
      energies 0.56eV, 0.33eV, 0.24eV, and 0.05eV respectively. The ac-conductivity of
      some published data are well fitted with the presented model and the total charge
      density in DNA molecule is calculated to be n=1.88*10(^19)cm(^-3) at 300K which
      is corresponding to a linear electron density n=8.66*10(^3)cm(^-1) at 300K. The
      model shed light on the role of transfer and/or localization of charges through
      DNA which has multiple applications in medical, nano-technical, bio-sensing and
      different domains. So, repair DNA by adjusting the charge transport through the
      molecule is future challenges to new medical applications.

PMID- 22959135
TI  - Analysis of novel ARG1 mutations causing hyperargininemia and correlation with
      arginase I activity in erythrocytes.
AB  - Hyperargininemia (HA) is an autosomal recessive disease that typically has a
      clinical presentation that is distinct from other urea cycle disorders. It is
      caused by the deficient activity of the enzyme arginase I, encoded by the gene
      ARG1. We screened for ARG1 mutations and measured erythrocyte enzyme activity in
      a series of 16 Brazilian HA patients. Novel mutations, in addition to previously
      described missense mutations, were analysed for their effect on the structure,
      stability and/or function of arginase I (ARG1) using bioinformatics tools. Three
      previously reported mutations were found (p.R21X; p.I11T and p.W122X), and five
      novel mutations were identified (p.G27D; p.G74V; p.T134I; p.R308Q; p.I174fs179).
      The p.T134I mutation was the most frequent in the Brazilian population. Patients
      carrying the p.R308Q mutation had higher residual ARG1 decreased activity, but
      presented no distinguishable phenotype compared to the other patients.
      Bioinformatics analyses revealed that missense mutations (1) affect the ARG1
      active site, (2) interfere with the stability of the ARG1 folded conformation or
      (3) alter the quaternary structure of the ARG1. Our study reinforced the role of
      Arg308 residue for assembly of the ARG1 homotrimer. The panel of heterogeneous
      ARG1 mutations that cause HA was expanded, nevertheless a clear genotype
      phenotype correlation was not observed in our series.

PMID- 22959136
TI  - A new partial trisomy 12p with artery catheter vagus, congenital cataracts,
      external auditory canal, and no turbinate.
AB  - We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 (p12
      pter) transmitted from a maternal reciprocal translocation 6;12. Genetic analysis
      was conducted on umbilical cord blood for a fetus accompanied with tricuspid
      regurgitation and orbital hypertelorism from a 27-year-old gravida 4, para 1
      after sonography at gestation 35 weeks. The karyotype was unusual, with 46, XY,
      der (6), t (6;12) (p24; p12) mat. The pregnancy was terminated at 37 gestational
      weeks. The aborted fetus displayed dysmorphic features of a round flat face with
      prominent cheeks and high forehead, hypertelorism, short nose, broad and
      depressed nasal bridge, anteverted nares, deformed philtrum, open mouth, thin
      upper vermilion and broad everted lower lip, low-set ears and aural atresia,
      broad hands with simian creases, and a short neck. Fetal anatomy showed right
      artery catheter vagus, congenital cataract, no turbinate and external auditory
      canals. Through karyotype-phenotype analysis of this patient and a review of
      other reported cases, we believe this is a first report that expands the database
      of partial trisomy 12p, and is beneficial for future clinical genetic counseling.
      This study supports that phenotypic variability depends on the type and extent of
      the associated partial monosomy.

PMID- 22959137
TI  - Meta-analysis of the association between body mass index and health-related
      quality of life among children and adolescents, assessed using the pediatric
      quality of life inventory index.
AB  - OBJECTIVE: To explore the relationships between body mass index and overall,
      physical, and psychosocial health-related quality of life (HRQoL) in children and
      adolescents. STUDY DESIGN: A systematic review was conducted in accordance with
      Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.
      Medline, Embase, PsycINFO, and the Web of Knowledge were searched for relevant
      articles. Inclusion was restricted to participants under 20 years of age,
      assessed using the Pediatric Quality of Life Inventory. Random-effects meta
      analysis, meta-regression, and cumulative meta-analysis were conducted.
      Heterogeneity was assessed using the I(2) statistic, and potential publication
      and small study bias were evaluated using funnel plots and the Egger test.
      RESULTS: Eleven eligible studies provided 35 estimates of effect size, derived
      from a total of 13210 study participants. Based on self-reports, children and
      adolescents with above-normal body mass index had significantly lower total,
      physical, and psychosocial HRQoL, with a clear dose relationship across all
      categories. In obese children and adolescents, the overall score was reduced by
      10.6 points (95% CI, 14.0-7.2; P < .001). Parents reported the same pattern but a
      larger effect size. The total parental score for obese children and adolescents
      was reduced by 18.9 points (95% CI, 26.6-11.1; P < .001). No significant
      publication or small study bias was observed. CONCLUSION: Parents overestimate
      the impact of obesity on the HRQoL of their children. Nonetheless, obese children
      and adolescents have significantly reduced overall, physical, and psychosocial
      HRQoL.

PMID- 22959138
TI  - Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving
      treatment doses of enoxaparin.
AB  - OBJECTIVE: To determine if using actual body weight to dose enoxaparin in obese
      pediatric patients results in higher anti-Xa levels compared with non-obese
      pediatric patients. STUDY DESIGN: This was a retrospective case-matched study of
      obese and non-obese pediatric patients receiving treatment doses of enoxaparin in
      a tertiary care children's hospital. Patients were included if they were
      initiated on treatment doses of enoxaparin, had appropriate anti-Xa levels drawn,
      and were between 2 and 18 years of age. Patients with renal insufficiency,
      hyperbilirubinemia, goal anti-Xa level <0.5 or >1 unit/mL, or receiving
      mechanical circulatory support were excluded. Obese patients who met study
      criteria were matched on a 1:1 basis with non-obese patients. RESULTS: All
      baseline characteristics were similar except for body mass index percentile (98.2
      +/- 2 vs 48.7 +/- 15, P < .01). Obese patients had higher initial anti-Xa levels
      (0.67 +/- 0.27 vs 0.53 +/- 0.24 unit/mL, P = .028). Over time, obese patients
      required a lower mean dose to achieve therapeutic anti-Xa levels than non-obese
      patients (0.81 +/- 0.19 vs 1.1 +/- 0.4 mg/kg, P = .005). CONCLUSIONS: The mean
      initial anti-Xa level was higher in obese pediatric patients compared with non
      obese pediatric patients, but a dosage adjustment was not required. Obese
      patients may need closer monitoring over time to avoid supratherapeutic levels
      and possible bleeding events.

PMID- 22959139
TI  - Pediatric idiopathic intracranial hypertension and extreme childhood obesity: a
      comment on visual outcomes.

PMID- 22959140
TI  - Papillary breast lesions diagnosed by core biopsy require complete excision.
AB  - BACKGROUND: Surgical excision of papillary breast lesions with atypia diagnosed
      using core needle biopsy (CNB) has been accepted; however, the management of
      benign papillary lesions (without atypia) has been controversial. The purpose of
      this study was to evaluate the surgical outcome of nonmalignant papillary lesions
      diagnosed by ultrasound-guided 14-gauge CNB, and to establish clear guidelines on
      management of these lesions. METHODS: We retrospectively identified 268
      nonmalignant papillary breast lesions, including 203 benign lesions and 65
      atypical lesions, diagnosed by CNB and subsequently surgically excised in 250
      women at our institution between July 2004 and October 2010. For each lesion,
      medical records and radiologic and pathologic reports were reviewed and coded. We
      compared the histological upgrade among the collected variables. RESULTS: On
      histological examination after surgical excision, 15.4% atypical papillary
      lesions and 5.9% benign lesions were upgraded to malignant, and 20.2% benign
      lesions were upgraded to atypical. Atypia (P = 0.015) was significantly
      associated with malignant upgrade at excision. No clinical or radiologic variable
      was helpful in predicting the possibility of histological upgrade of CNB
      diagnosed nonmalignant papillary lesions. CONCLUSIONS: Nonmalignant papillary
      lesions diagnosed with CNB showed an unacceptable pathological upgrade rate after
      excision. Therefore, surgical excision should be performed for all papillary
      lesions of the breast for definitive diagnosis.

PMID- 22959141
TI  - Chylomicron retention disease.

PMID- 22959142
TI  - Abnormal fetomaternal glucocorticoid metabolism in the background of premature
      delivery: placental expression patterns of the 11beta-hydroxysteroid
      dehydrogenase 2 gene.
AB  - OBJECTIVE: During pregnancy, 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2)
      is involved in the development of the placental barrier, and its main function is
      to protect the fetus from the effects of the physiological increase of maternal
      glucocorticoids. We compared human placental gene expression patterns of 11beta
      HSD2 from pregnancies that ended with preterm delivery versus full term
      pregnancies as controls. STUDY DESIGN: We used real-time PCR to assess the
      placental gene expression patterns of 11beta-HSD2 in 104 preterm and 140 full
      term pregnancies (control group) at the time of delivery. RESULTS: In the preterm
      delivery group, the proportion of smokers was 26.9%, significantly higher than in
      the control group. Preterm delivery began with premature rupture of membranes in
      70.2% and spontaneous uterine activity in 29.8%. The 11beta-HSD2 gene was
      underexpressed in the preterm delivery group compared to normal pregnancy between
      28 and 36 gestational weeks, but unchanged between 24 and 28 weeks. There was no
      fetal gender effect on 11beta-HSD2 gene expression. CONCLUSION: The reduced
      activity of the 11beta-HSD2 gene seen in the preterm delivery group may impair
      fetal defences against maternal glucocorticoid exposure. In cases of impending
      premature delivery, glucocorticoid effects, potentially including postnatal
      neurological abnormalities and growth restriction, may be worsened by
      prophylactic steroids given to accelerate fetal lung maturity. The impairment in
      fetal defences against maternal glucocorticoids due to reduced 11beta-HSD2 enzyme
      activity appears to begin after gestational week 28.

PMID- 22959143
TI  - Dynamin 2 expression as a biomarker in grading of cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE: Dynamin 2, which plays a role in endocytosis, is known to be required
      for HPV infection on host cells. We investigated dynamin 2 as a biomarker in
      grading of cervical intraepithelial neoplasia (CIN) by comparing with Ki-67
      expression and the type of HPV infection (low-risk vs. high-risk). STUDY DESIGN:
      We performed immunohistochemical stains of dynamin 2 and Ki-67 on tumor samples
      of patients with CIN and the type of HPV infection was investigated. RESULTS: All
      the patients with reactive changes (n=7) or normal (n=4) did not show dynamin 2
      expression. There were 33, 14, and 12 cases with CIN I, II, and III,
      respectively, and there was a negative correlation between the degree of dynamin
      2 expression and the severity of CIN lesions with statistical significance
      (P<0.001). Negative expression of dynamin 2 was more sensitive for the detection
      of CIN II/III than high expression (2+) of Ki-67 (96.2% vs. 73.1%, P=0.041).
      Among patients in whom HPV infection was detected, the degrees of dynamin 2
      expression were not associated with the type of HPV infection (low-risk vs. high
      risk). Overall, there was a negative correlation between the expression patterns
      of Ki-67 and dynamin 2. CONCLUSION: We found that dynamin 2 may be a helpful
      biomarker in grading of CIN lesions and a candidate biomarker for detecting low
      grade CIN with high sensitivity.

PMID- 22959144
TI  - Outcome of midurethral tape continence surgery in patients with and without
      urodynamically confirmed stress incontinence.
AB  - OBJECTIVE: To compare the outcomes of midurethral tape continence surgery in
      patients with urodynamically confirmed stress incontinence (USI) and patients
      with symptoms of stress urinary incontinence but normal urodynamic studies (NUDS)
      and a positive 1-h pad test. STUDY DESIGN: Analysis of data collected
      prospectively from 356 women who underwent tension-free vaginal tape (TVT)
      surgery from June 1998 to September 2009. There were 25 women with NUDS but a
      positive pad test. Outcome measures in these 25 women were compared with 65 women
      with urodynamically confirmed stress incontinence. These 65 women were chosen as
      suitable controls from the group of 331 potential controls. All the women
      underwent TVT surgery under local or spinal anaesthesia. RESULTS: The outcome
      measures were: (1) absence of stress urinary incontinence symptoms, (2) new
      occurrence of lower urinary tract irritative symptoms (LUTS), (3) persistent
      voiding dysfunction (VD), and (4) recurrent urinary tract infections (UTIs).
      Following TVT, stress incontinence was absent in 100% and 97% of patients in the
      NUDS and USI groups respectively. The occurrence of LUTS was 4% and 4.6% in the
      NUDS and USI groups, while VD was found in 4% and 4.6% and recurrent UTIs in 8%
      and 6.1% of the groups respectively. CONCLUSION: There were no significant
      differences in outcomes following TVT in patients with and without urodynamically
      confirmed stress urinary incontinence.

PMID- 22959145
TI  - Oxidative imbalance and anxiety in patients with sleep bruxism.
AB  - OBJECTIVE: We evaluated the relationship among sleep bruxism (SB),
      antioxidant/oxidant status, and anxiety level to determine whether
      antioxidant/oxidant status may be used as a biological marker of SB. STUDY
      DESIGN: Thirty-three SB and 32 healthy patients of similar age, sex, and body
      mass index were enrolled, venous blood was collected, and anxiety scores were
      determined. Plasma samples were analyzed for total oxidant status, antioxidant
      status, and oxidative stress index. RESULTS: In 2 of the 3 assays performed, SB
      patients exhibited an oxidative imbalance. A higher anxiety score was observed
      with SB (P < 0.05). CONCLUSIONS: These results show that oxidant/antioxidant
      imbalance may be related to SB, either pathophysiologically or as an outcome of
      the condition. Further biochemical studies could prove useful in determining the
      importance of antioxidant drugs in the treatment of SB.

PMID- 22959146
TI  - Adverse drug reactions to local anesthetics: a systematic review.
AB  - OBJECTIVE: The aim of this study was to analyze adverse drug reactions (ADRs)
      associated with local anesthetics (LAs) and to characterize the safety profile of
      LAs in clinical application. STUDY DESIGN: Electronic databases were searched,
      and the data of the included articles were extracted and analyzed. RESULTS: A
      total of 922 articles were retrieved, and 101 of them, containing 1,645 events,
      were included. Lidocaine (43.17%) and bupivacaine (16.32%) were the most often
      involved LAs. Epinephrine (45.37%) was mostly combined with LAs. Cardiovascular
      system reactions (27.83%) were the most involved systematic ADRs of LAs. Among 7
      death events (3.54%), 2 patients died of intravascular injection. According to
      the meta-analysis, the risk of using LA alone was lower than combined with
      epinephrine. CONCLUSIONS: The present study demonstrated that the ADRs of LAs
      could not be ignored, especially in oral and ophthalmologic treatments. Some ADRs
      could be avoided by properly evaluating the conditions of patients and correctly
      applying LAs.

PMID- 22959147
TI  - Analysis of nonspecific oral mucosal and dermal lesions suggestive of syphilis: a
      report of 6 cases.

PMID- 22959148
TI  - Clinical and polysomnographic characteristics and response to continuous positive
      airway pressure therapy in obstructive sleep apnea patients with nightmares.
AB  - OBJECTIVE: To assess the characteristics of obstructive sleep apnea (OSA)
      patients with nightmares and the effects of continuous positive airway pressure
      (CPAP) therapy on nightmares. METHODS: Consecutive patients referred with a
      clinical suspicion of OSA underwent attended overnight sleep studies. OSA and
      nightmares were diagnosed according to the American Academy of Sleep Medicine
      (AASM) criteria, and CPAP titration was performed in accordance with the AASM
      guidelines. A follow-up visit was performed 3months later, and the patients with
      nightmares were divided into two groups: group 1 used CPAP with good compliance,
      whereas group 2 refused CPAP treatment and did not use other alternative
      treatments for OSA. RESULTS: The study included 99 patients who had been
      diagnosed with OSA with nightmares. Their mean age was 47.2+/-11.2years, and they
      had a mean apnea-hypopnea index (AHI) of 36.5+/-34.3/h. Also included were 124
      patients with OSA without nightmares. The mean age of these patients was 45.4+/
      13.9years, and they had a mean AHI of 40.2+/-35/h. The patients with nightmares
      had a significantly higher AHI during rapid eye movement sleep (REM) compared
      with the patients without nightmares (51.7+/-28.1 vs 39.8+/-31.9/h). Logistic
      regression analysis revealed that the REM-AHI and interrupted sleep at night were
      independent predictors of nightmares in the OSA patients. Nightmares disappeared
      in 91% of the patients who used CPAP compared with 36% of patients who refused to
      use CPAP (p<0.001). CONCLUSION: Nightmares in OSA patients are associated with a
      higher REM-AHI. CPAP therapy results in a significant improvement in nightmare
      occurrence.

PMID- 22959149
TI  - Computational multiscale modeling of embryo development.
AB  - Recent advances in live imaging and genetics of mammalian development which
      integrate observations of biochemical activity, cell-cell signaling and
      mechanical interactions between cells pave the way for predictive mathematical
      multi-scale modeling. In early mammalian embryo development, two of the most
      critical events which lead to tissue patterning involve changes in gene
      expression as well as mechanical interactions between cells. We discuss the
      relevance of mathematical modeling of multi-cellular systems and in particular in
      simulating these patterns and describe some of the technical challenges one
      encounters. Many of these issues are not unique for the embryonic system but are
      shared by other multi-cellular modeling areas.

PMID- 22959150
TI  - Investigating the principles of morphogen gradient formation: from tissues to
      cells.
AB  - Morphogen gradients regulate the patterning and growth of many tissues, hence a
      key question is how they are established and maintained during development.
      Theoretical descriptions have helped to explain how gradient shape is controlled
      by the rates of morphogen production, spreading and degradation. These effective
      rates have been measured using fluorescence recovery after photobleaching (FRAP)
      and photoactivation. To unravel which molecular events determine the effective
      rates, such tissue-level assays have been combined with genetic analysis, high
      resolution assays, and models that take into account interactions with receptors,
      extracellular components and trafficking. Nevertheless, because of the natural
      and experimental data variability, and the underlying assumptions of transport
      models, it remains challenging to conclusively distinguish between cellular
      mechanisms.

PMID- 22959151
TI  - Electrically induced lipid migration in non-lamellar phase.
AB  - Inverted hexagonal blocks of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)
      lipid adsorbed on a polyethyleneimine (PEI)-coated surface in deionized water
      transformed its shape upon the application of an electric field, forming lipid
      objects in a variety of shapes (e.g. lines with a width of 10-50 MUm). The
      phenomenon was driven by the electrophoresis, because the zwitterionic lipid,
      DOPE turned out to be highly negatively charged in deionized water. The
      interaction between DOPE and the PEI surface stabilized the system, assuring a
      lifetime over several weeks for the formed structures after the electric field
      was switched off. The free-drawing of microscopic objects (lines, crosses, and
      jelly fish) was also achieved by controlling the direction of the lipid movement
      with the field direction.

PMID- 22959152
TI  - Transesophageal echocardiography is more sensitive than transthoracic
      echocardiography in detecting residual atrial septal defect at the inferior vena
      caval end.

PMID- 22959153
TI  - Thrombotic endotracheal tube occlusion after administration of recombinant factor
      VIIa.

PMID- 22959154
TI  - High left ventricular vent return after left and right ventricular assist device
      placement in a patient with a mechanical aortic valve.

PMID- 22959155
TI  - Successful waste management strategies in developing countries require meaningful
      involvement of the concerned stakeholders.

PMID- 22959156
TI  - Kinetic modeling of enzymatic hydrolysis of pretreated kitchen wastes for
      enhancing bioethanol production.
AB  - It is well known that use of low cost and abundant waste materials in microbial
      fermentations can reduce product costs. Kitchen wastes disposed of in large
      amounts from cafeterias, restaurants, dining halls, food processing plants, and
      household kitchens contain high amounts of carbohydrate components such as
      glucose, starch, and cellulose. Efficient utilization of these sugars is another
      opportunity to reduce ethanol costs. In this study, the effect of pretreatment
      methods (hot water, acid solutions, and a control) on enzymatic hydrolysis of
      kitchen wastes was evaluated using a kinetic modeling approach. Fermentation
      experiments conducted with and without traditional fermentation nutrients were
      assessed at constant conditions of pH 4.5 and temperature of 30 degrees C for 48h
      using commercial dry baker's yeast, Saccharomyces cerevisiae. The control, which
      involved no treatment, and hot water treated samples gave close glucose
      concentrations after 6h. The highest and lowest rates of glucose production were
      found as 0.644 and 0.128 (h(-1)) for the control (or no-pretreated (NPT)) and 1%
      acid solutions, respectively. The fermentation results indicated that final
      ethanol concentrations are not significantly improved by adding nutrients (17.2
      23.3g/L). Thus, it was concluded that product cost can be lowered to a large
      extent if (1) kitchen wastes are used as a substrate, (2) no fermentation
      nutrient is used, and (3) hydrolysis time is applied for about 6h. Further
      optimization study is needed to increase the yield to higher levels.

PMID- 22959157
TI  - The United Kingdom and Ireland Trauma & Orthopaedic eLogbook--an evidence base
      for enhancing training.
AB  - The United Kingdom and Ireland Trauma and Orthopaedic (T&O) eLogbook was
      originally conceived over ten years ago in order to provide individual surgeon
      support and allow national analysis of surgical training experience. Since 2003
      every trainee in T&O has been required to submit data recording their operative
      experience throughout the six years of higher specialist training. We describe
      how orthopaedic surgeons are using the evidence from the eLogbook to improve
      training, set operative standards and support consultant (post-specialist
      registration) revalidation.

PMID- 22959158
TI  - An alternative method for predicting size of femoral component of Oxford partial
      knee replacement.
AB  - BACKGROUND: No direct intra-operative measurement to determine the ideal size of
      the femoral component of Oxford unicompartmental knee replacement (UKR) is
      currently present. The aim of this study is to assess the accuracy of patients'
      shoe size as a predictor of femoral component size. METHODS: A retrospective
      study was conducted to identify the correlation between patients' shoe size
      (British system) and the femoral component size. After excluding patients who
      died (n = 2) and patients in whom the implanted femoral component size was
      inaccurate (n = 13), the remaining cases (93 UKR in 88 patients) formed the study
      sample. Postoperative radiographs were reviewed to determine femoral component
      fit. RESULTS: We found positive correlation between shoe size and femoral
      component size. In females; a shoe size from 2.5 to 6 predicted a small femoral
      component and shoe size from 6.5 to 8.0 predicted a medium femoral component. In
      males, a shoe size from 6 to 9.5 predicted a medium femoral component and a shoe
      size from 10 to 13 predicted a large femoral component. This relation predicted
      the femoral component size accurately in 80% of cases. A subgroup analysis, after
      excluding patients who changed their shoe size during adulthood after foot
      surgery or pathology (n = 20), showed an accuracy rate of 81%. CONCLUSION: Shoe
      size is a simple method that predicts femoral component size more accurately than
      other methods currently used such as templating, tibial component size and height
      based on gender.

PMID- 22959159
TI  - Pre-operative predictors of post-hepatectomy recurrence of hepatocellular
      carcinoma: can we predict earlier?
AB  - BACKGROUNDS AND PURPOSE: To determine the predictors for recurrence in patients
      receiving curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: From
      January 2001 to July 2007, all patients having hepatectomy for first occurrence
      HCC with curative intent were identified from a prospectively collected database.
      Prognostic factors for recurrence and survival after resection were analyzed.
      RESULTS: A total of 235 patients were included. With a median follow-up of 50.2
      (0.07-125.1) months, the recurrence rate was 57.0%. The 1-, 3-, and 5-year
      overall survival rates were 83.9%, 66.0%, and 58.1% respectively. Multivariate
      analysis demonstrated that multi-focal lesions (HR: 2.93, P < 0.001), alpha
      fetoprotein (AFP) level greater than 100 ng/ml (HR: 1.74, P = 0.002) and history
      of tumor rupture (HR: 2.84, P = 0.003) were independent risk factors for
      recurrence of HCC after hepatectomy. CONCLUSIONS: Predictors for HCC recurrence
      can be identified before operation. These important parameters should be
      considered before and after contemplating curative resection for HCC patients and
      for risk stratification in future clinical trials for neoadjuvant or post
      resection adjuvant therapy. The possible use of neoadjuvant or adjuvant treatment
      to improve survival should be addressed by further trials.

PMID- 22959160
TI  - Laparoscopic adrenalectomy: auditing the 10 year experience of a single centre.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for benign
      adrenal resection, and has been performed at our centre since 2000. We present a
      retrospective audit of our ten-year experience, and discuss the learning curve.
      METHODS: Creating a retrospective database, clinical and outcome data were
      collected for all resections performed over a ten-year period (2000-2010).
      Patients were chronologically divided into an 'early' (first 40 cases) and 'late'
      (subsequent cases) group to provide an insight into the learning curve. RESULTS:
      Over this period, 134 laparoscopic resections were performed, predominantly for
      benign adenomas (80.3%), with 48% of patients having primary hyperaldosteronism.
      There was almost equal sex distribution and mean age was 50.2 years, with a
      median BMI of 28.2. The mean operating time for left and right procedures were
      127 and 124 min respectively, with 56.7% of resections being left sided. Our rate
      of conversion to open was 3.9%. Median length of stay was 4 days post
      operatively. There was no mortality and 8.7% patients experienced a surgical
      complication. Analysis of the grouped data demonstrated a statistically
      significant reduction in open conversion rate (p = 0.017) and operative time (p =
      0.011) in the 'late' group. Among the two groups there was no statistically
      significant difference in the length of stay and surgical complication rate. All
      results were comparable to published series in the literature. CONCLUSION: LA has
      proven to be a safe procedure with a low complication rate at our centre. Our
      data provide evidence that operative time and conversion rate improves with
      experience.

PMID- 22959161
TI  - A comparison of the teamwork attitudes and knowledge of Irish surgeons and U.S
      Naval aviators.
AB  - Poor teamwork skills are contributors to poor performance and mishaps in high
      risk work settings, including the operating theatre. A questionnaire was used to
      assess the attitudes towards, and knowledge of, Irish surgeons (n = 72) towards
      the human factors that contribute to mishaps and poor teamwork in high risk
      environments. The responses were compared to those obtained from U.S. Naval
      aviators (n = 552 for the attitude questions, and n = 172 for the knowledge
      test). U.S. Naval aviators were found to be significantly more knowledgeable, and
      held attitudes that were significantly more positive towards effective
      teamworking than the surgeons. Moreover, 78.9% of Senior House Officers and
      Registrars stated that junior personnel were frequently afraid to speak-up
      (compared with 31.3% of Consultants). Only 7.3% of surgeons stated that an
      adequate pre-operative brief team brief was frequently conducted, and only 15%
      stated that an adequate post-operative team brief was frequently conducted. It is
      suggested that the human factors training currently provided to surgeons in
      Ireland is a positive first step. However, there is a need to stress the
      importance of assertiveness in juniors, listening in seniors, and more
      reinforcement of good teamworking behaviours in the operating theatre.

PMID- 22959162
TI  - Food webs: reconciling the structure and function of biodiversity.
AB  - The global biodiversity crisis concerns not only unprecedented loss of species
      within communities, but also related consequences for ecosystem function.
      Community ecology focuses on patterns of species richness and community
      composition, whereas ecosystem ecology focuses on fluxes of energy and materials.
      Food webs provide a quantitative framework to combine these approaches and unify
      the study of biodiversity and ecosystem function. We summarise the progression of
      food-web ecology and the challenges in using the food-web approach. We identify
      five areas of research where these advances can continue, and be applied to
      global challenges. Finally, we describe what data are needed in the next
      generation of food-web studies to reconcile the structure and function of
      biodiversity.

PMID- 22959163
TI  - Reforms in the Greek pharmaceutical market during the financial crisis.
AB  - INTRODUCTION: Following the financial crisis of 2008, Greece has been facing
      severe fiscal problems associated with high public debt and deficit. Given their
      significant contribution to public sector expenditure, part of the effort to
      reduce public expenditure has involved a focus on pharmaceutical markets.
      METHODS: Our aim is to provide an overview of recent policy changes in the Greek
      pharmaceutical market as a response to the crisis. We also discuss other
      potential measures that can be implemented. The recommendations are relevant to
      European countries facing debt crises, but also to any other country, as
      improving efficiency makes funds available to be used on other interventions.
      RESULTS: In 2010 and 2011, following the debt crisis and the agreement with the
      IMF, EU and ECB, the Greek government introduced several policy measures aimed at
      cost-containment. These changes included (a) price cuts, (b) the re-introduction
      of a positive list, (c) changes in the profit margins of pharmacies and
      wholesalers, and (d) tenders for hospital drugs. As a result, public drug
      expenditure decreased from ?5.09 billion in 2009 to ?4.25 billion in 2010 and
      ?4.10 billion in 2011. CONCLUSION: As the need to cut expenditure becomes more
      urgent, seeking efficiency is possibly the only option for countries that do not
      wish to compromise quality of healthcare and public health. However, efficiency
      and cost containment are not only about introducing new policies, but also about
      the enforcement of existing laws and fighting corruption.

PMID- 22959164
TI  - An international strategy to determine the role of high dose therapy in recurrent
      Wilms' tumour.
AB  - PURPOSE: To review event-free (EFS) and overall survival (OS) from publications
      describing outcome for children with relapsed Wilms' tumour. Comparisons are made
      between those receiving myeloablative high dose chemotherapy with autologous stem
      cell rescue (HDT) and those not (NoHDT). MATERIALS AND METHODS: Relevant
      information was extracted from individual patient or summary data and 3-year EFS
      and OS rates established. These rates were combined in a weighted manner to
      derive hazard ratios (HRs). RESULTS: Nineteen publications were identified (5
      HDT, 6 NoHDT, 8 both). Pooling all studies suggested an advantage to HDT with a
      hazard ratio (HR) for EFS of 0.87 (95% confidence interval (CI) 0.67-1.12) and
      0.94 (0.71-1.24) for OS. A stratified analysis confined to studies that provided
      individual patient data on both HDT and NoHDT gave HRs of 0.83 (0.56-1.24) and
      0.92 (0.59-1.41). Further, analyses of risk groups, defined by treatment and/or
      histology prior to first relapse, suggested a HR for EFS of 0.90 (95% CI 0.62
      1.31) for those of high and 0.50 (CI 0.31-0.82) for the very high risk patients.
      CONCLUSION: The evidence suggests, although there are many caveats since the
      information summarised here is not from randomised trials, a great deal of
      uncertainty concerning the role of HDT in patients following relapse after
      treatment for their Wilms' tumour. For each risk group we propose a randomised
      trial comparing a standard with a more intensive therapy with specific choice of
      regimen tailored to the risk group (and co-operative groups) concerned. A
      synthesis of updated evidence from studies in this overview together with any
      emerging studies and future trial information will form the basis for future
      evidence-based clinical decision-making.

PMID- 22959165
TI  - Momentary emotion surrounding bulimic behaviors in women with bulimia nervosa and
      borderline personality disorder.
AB  - BACKGROUND: Bulimia nervosa (BN) and borderline personality disorder (BPD) are
      disorders that involve emotion dysregulation, for negative emotion in particular,
      as well as impulsive behaviors beyond binge eating and vomiting. Given these
      similarities in psychopathology, it is not surprising that those with BN also
      present with BPD in approximately one third of cases. Improved understanding of
      similarities and differences in the experience of negative and positive emotion
      could aid in the development of treatments specifically tailored to the needs of
      these disorders. METHODS: In this study, we examined Ecological Momentary
      Assessment (EMA) data from 133 women diagnosed with BN, 25 of whom also exhibited
      diagnostic levels of BPD. Emotions and behaviors were assessed daily, with
      multiple random and event-contingent signals to complete questionnaires on
      portable digital devices, for a period of two weeks. RESULTS: Results indicated
      that the BPD group experienced higher negative emotional variability on bulimic
      event days. Both groups also demonstrated increasing negative emotion and
      decreasing positive emotion pre- binge eating and vomiting, with levels of
      negative emotion decreasing and positive emotion increasing after, for both
      behaviors. CONCLUSIONS: In terms of group differences, additive effects were
      found for the BN comorbid with BPD group, who demonstrated greater negative
      emotional variability, on bulimic event days, and also had higher overall levels
      of negative emotion pre- and post-binge eating. Those with BN only, however,
      displayed increasing trajectories of positive emotion before and after binge
      eating and after vomiting, indicating a potential emotional dampening effect of
      BPD.

PMID- 22959166
TI  - Treatment outcomes and unfavorable prognostic factors in patients with occult
      breast cancer.
AB  - AIMS: The purpose of this study was to evaluate the treatment outcomes and
      prognostic factors in patients with occult breast cancer (OBC). METHODS: We
      retrospectively analyzed 95 patients with OBC who were treated at our facility
      between January 1998 and June 2010. Of the 95 patients, 64 underwent mastectomy
      plus axillary lymph node dissection (ALND) with or without post-mastectomy
      radiation (Mast + ALND group), 13 underwent ALND followed by ipsilateral breast
      radiotherapy (BR + ALND group) and the remaining 18 were treated with ALND (ALND
      group). RESULTS: Patients who underwent Mast + ALND or BR + ALND had
      significantly improved rates of locoregional recurrence-free survival (LRFS) and
      recurrence/metastasis-free survival (RFS) than patients who only underwent ALND
      (p < 0.05). There were no significant differences in the LRFS (p = 0.718), RFS (p
      = 0.935) and breast cancer-specific survival (BCSS) (p = 0.991) rates between the
      patients who underwent Mast + ALND compared with those who received BR + ALND.
      Multivariate analysis revealed that patients with four or more involved lymph
      nodes had significantly worse outcomes (p = 0.042, HR = 4.63, 95% CI = 1.66-32.47
      for BCSS and p = 0.038, HR = 3.62, 95% CI = 1.08-20.77 for RFS). CONCLUSIONS:
      Patients with OBC who received ALND and subsequent breast radiotherapy had
      similar outcomes to patients who underwent mastectomy. The presence of four or
      more involved lymph nodes may independently predict poor outcomes of OBC.

PMID- 22959167
TI  - The cellular level of histone H3 lysine 4 dimethylation correlates with response
      to adjuvant gemcitabine in Japanese pancreatic cancer patients treated with
      surgery.
AB  - BACKGROUND: To search for biomarkers identifying pancreatic cancer patients
      likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the
      status of several histone modifications in pancreatic tumors and their
      relationship to clinicopathological features and outcomes. METHODS: Sixty one
      pancreatic cancer patients, primarily treated by surgical removal of tumors, were
      involved in the study. Thirty patients completed postoperative adjuvant
      gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using
      immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2
      and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and
      H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor
      staining for each histone modification was used to classify patients into low-
      and high-staining groups, which were examined for relationships to
      clinicopathological features and clinical outcomes. RESULTS: High expression of
      H3K4me3 was related to the well and moderately differentiated tumor histological
      type (p = 0.012) and low expression of H3K4me2 was related to the presence of
      perineural invasion (p = 0.007). No cellular histone modifications were
      associated with overall or disease-free survival of patients as a whole. In the
      subgroup analyses, a low level of H3K4me2 was significantly associated with worse
      disease free survival in patients that completed adjuvant gemcitabine (p =
      0.0239). Univariate and multivariate hazard models also indicated that a low
      level of H3K4me2 was a significant independent predictor of disease-free survival
      (p = 0.007). CONCLUSION: H3K4me2 was found to be a predictor of response to
      adjuvant gemcitabine in Asian patients with pancreatic cancer.

PMID- 22959168
TI  - Home-management of malignant pleural effusion with an indwelling pleural
      catheter: ten years experience.
AB  - BACKGROUND: More than one half of patients with cancer have a malignant pleural
      effusion (MPE) at some time during their life span. Recurrent malignant pleural
      effusions impair respiratory functions and worsen the quality of life. Once a
      patient develops MPE, only fluid drainage relieves pulmonary compression and
      dyspnea. Optimal treatment is however, still controversial. In patients not
      suitable for pleurodesis, or with recurrent MPE after pleurodesis, or with
      trapped lung, the outpatient intermittent drainage through a subcutaneous
      tunneled indwelling pleural catheter (IPC) is a possible choice. METHODS: In ten
      years, we treated 90 patients by outpatient insertion of IPC. Eligibility for IPC
      required previous thoracentesis with histological confirmation of malignancy and
      chest roentgenogram evidence of effusion. All patients treated were made aware of
      their malignancy and positive cytology in the pleural effusion. RESULTS: Mean
      survival was 197 days (range 23-296 days). Median time of draining interval was
      7.0 days with maximum amount of effusion drained off being 1000 ml. Pleurodesis
      occurred in 37 (41.1%) patients with a mean time of pleurodesis of 51 days (range
      34-78 days). No major complication was recorded. CONCLUSIONS: The IPC is a useful
      device in the management of recurrent MPE. Treatment can be entirely accomplished
      at home and the complication rate is low.

PMID- 22959169
TI  - [How to easily and efficiently implement a quality improvement project regarding
      sedation-analgesia in Intensive care unit?].

PMID- 22959170
TI  - [Assessment of an educational maze for major trauma care teaching].
AB  - BACKGROUND: Assess efficacy, satisfaction and usefulness of an educational maze
      based on posters and audioguide for major trauma care teaching to medical
      students. The educational maze consists of posters with audio comments recorded
      in an audioguide. This tool was part of a larger educational program including
      medical simulation. STUDY DESIGN: Prospective, interventional, observational,
      monocentric study. STUDENT: Medical student of Grenoble University Hospital, in
      the four last years of medical school, following a training course in anesthesia,
      emergency medical services and intensive care units. METHOD: Forty essentials key
      messages for major trauma management were included in 10 posters and audioguides.
      A first assessment with short opened answers was handed to the students at the
      end of the educational maze to assess their memorization. A second assessment
      with simple choice answers regarding satisfaction and usefulness of this new
      educational tool was realized at the end of the entire program. RESULT: One
      hundred and eighty-four medical students attending the major trauma program were
      included in this study. On the first test, 75% of essential knowledge on major
      trauma management was memorized by more than 50% of the medical students. On the
      second test, 94% of medical students had a high satisfaction level of this
      educational maze. CONCLUSION: An educational maze based on posters and
      audioguides seems to be an efficient, useful tool for teaching essential
      knowledge on major trauma management to medical students.

PMID- 22959171
TI  - MDCT imaging of calcinosis in systemic sclerosis.
AB  - Calcinosis is a typical feature of systemic sclerosis (SSc) and can be found in
      many different tissues including the superficial soft tissues, periarticular
      structures, muscles, and tendons. It can also provoke erosive changes on bones.
      Investigation is conducted most often with plain radiographs. However, when a
      more detailed assessment is necessary, multidetector computed tomography (MDCT)
      is helpful owing to its multiplanar reformat (MPR) ability. The purpose of this
      review is to provide an overview of the various appearances of calcinosis in SSc
      patients as visualized at MDCT.

PMID- 22959172
TI  - Vertebral fracture prevalence in a referral population of 750 Canadian men and
      women.
AB  - AIM: To establish the prevalence of vertebral fracture (VF) in a representative
      sample of 750 Canadians and to examine the relationships between VF prevalence
      and bone mineral density (BMD) at the spine and proximal femur. MATERIALS AND
      METHODS: X-ray-based dual-photon absorptiometry (DXA) was used to perform
      measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA).
      RESULTS: Two hundred and fifty-nine VFs were identified in 156 patients and the
      prevalence of unknown or unsuspected VF was 18.7%. For premenopausal women and
      for men, there was no difference in BMD at either the spine or the hip whether or
      not there was at least one VF. For postmenopausal women, BMD of the total region
      of the proximal femur was statistically lower (p < 0.001) in women with at least
      one VF whereas spine BMD only tended to be less (0.10 > p > 0.05). Proximal femur
      BMD was lower for postmenopausal women with more VF, while spine BMD was
      virtually unchanged as the number of VF increased. Neither spine nor hip BMD was
      lower for men with more VF. A strong association was observed in postmenopausal
      women between an age-dependent increase in VF prevalence and a reduction in
      femoral BMD. Such an association was not present in men. CONCLUSION: VFs are
      common, are often independent of either spine or hip BMD, and frequently go
      unnoticed. Therefore, VFA should be part of a routine assessment of fracture
      risk.

PMID- 22959173
TI  - Laboratory testing protocol for the impact of dispersed petrochemicals on
      seagrass.
AB  - To improve the effectiveness of oil spill mitigation, we developed a rapid,
      logistically simple protocol to detect petrochemical stress on seagrass. Sections
      of leaf blades from Zostera muelleri subsp. capricorni were exposed to the water
      accommodated fraction (WAF) of non-dispersed and dispersed Tapis crude oil and
      fuel oil (IFO-380) for 5h. Photosynthetic health was monitored by assessing
      changes in effective quantum yield of photosystem II (DeltaF/F(m)(')) and
      chlorophyll a pigment concentrations. Loss of total petroleum hydrocarbons (TPH)
      was measured using an oil-in-water fluorometer, whilst GC-MS analyses quantified
      the hydrocarbon components within each treatment. Few significant differences
      were detected in the chlorophyll a pigment analyses; however, DeltaF/F(m)(')
      appeared sensitive to petrochemical exposure. Dispersing both types of oil
      resulted in a substantial increase in the TPH of the WAF and was generally
      correlated with a greater physiological impact to the seagrass health, compared
      with the oil alone.

PMID- 22959174
TI  - Provenance of Corexit-related chemical constituents found in nearshore and inland
      Gulf Coast waters.
AB  - The dispersants Corexit 9527 and Corexit 9500 were extensively used during the
      response to the Deepwater Horizon accident in 2010. In addition to the monitoring
      programs established by federal and state governments, local communities also
      conducted studies to determine if chemical constituents from these dispersants
      impacted nearshore and inland waters. One community (the City of Orange Beach,
      Alabama) collected water samples between September, 2010 and January, 2011, and
      found the dispersant-related chemicals propylene glycol, 2-butoxyethanol, and
      dioctyl sodium sulfosuccinate at nearshore and inland water sampling sites. In
      this paper, we examine their dataset in an attempt to discern the origin of these
      chemicals. Our assessment indicates that these compounds are unlikely to be
      present as a result of the use of Corexit dispersants; rather, they are likely
      related to point and non-point source stormwater discharge.

PMID- 22959175
TI  - Decadal change in sublittoral macrofaunal biodiversity in the Bohai Sea, China.
AB  - The region of the Bohai Sea is among the most densely populated of any marginal
      sea worldwide, and the sea is of great commercial importance as one of the major
      fishing areas in China. In this study, sublittoral macrofaunal community data
      collected during the 2000s was integrated with historical data from the 1980s to
      1990s to detect any change in biodiversity status over the past three decades.
      Biodiversity was assessed through species diversity, taxonomic relatedness and
      other measures of community structure. Different geographic locations had
      different scenarios of decadal biodiversity change. We observed a sustained
      increase in species diversity in Bohai Bay and a cyclic trajectory in Laizhou
      Bay. In the central part of the Bohai Sea, there was little change in species
      diversity, whereas taxonomic distinctness tended to increase. A test for
      departure from the expected value of taxonomic distinctness (Delta(+), Lambda(+))
      suggested that approximately one-fifth of the sampling stations were subjected to
      environmental stress and perturbation.

PMID- 22959176
TI  - Benign hereditary chorea: clinical features and long-term follow-up in a Spanish
      family.

PMID- 22959179
TI  - Sudden death.
AB  - Sudden death is probably the greatest challenge in modern cardiology. After
      reviewing its history, we describe the epidemiology of sudden death and its
      associated diseases. We highlight its physiopathologic aspects, including the
      factors that act on vulnerable myocardium triggering the final arrhythmia, mainly
      ventricular fibrillation and, to a lesser extent, bradycardia and sudden death.
      We emphasize the relevance of acute ischemia, ventricular dysfunction and genetic
      factors, not only in genetic heart disease, but also as triggers of sudden death
      in acute and chronic ischemic heart disease. Finally, we describe the best way to
      identify candidates at risk, discuss how to prevent sudden death, and outline the
      best approach to managing a patient resuscitated from cardiac arrest. Full
      English text available from:www.revespcardiol.org.

PMID- 22959180
TI  - Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of
      vascular metabolism in tumors.
AB  - Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin
      adenine dinucleotide (FAD) are essential for normal cellular growth and function.
      Their intracellular transport is regulated by the riboflavin carrier protein
      (RCP), which has been shown to be over-expressed by metabolically active cancer
      cells. Therefore, FAD-decorated ultrasmall superparamagnetic iron oxide
      nanoparticles (FAD USPIO) were developed as the first carrier-protein-targeted
      molecular MR agents for visualizing tumor metabolism. FAD USPIO were synthesized
      using an adsorptive, fluorescent and non-polymeric coating method, and their
      physicochemical properties were characterized using TEM, SEM, FTIR, MRI and
      fluorescence spectroscopy. In vitro analyses showed the biocompatibility of FAD
      USPIO, and confirmed that they were strongly and specifically taken up by cancer
      (LnCap) and endothelial (HUVEC) cells. In vivo molecular MRI together with
      subsequent histological validation finally demonstrated that FAD USPIO
      efficiently accumulate in tumors and tumor blood vessels, indicating that RCP
      targeted diagnostic nanoparticles are interesting new materials for the
      assessment of vascular metabolism in tumors.

PMID- 22959182
TI  - Labeling cells for in vivo tracking using (19)F MRI.
AB  - Noninvasive in vivo cell tracking is crucial to fully understand the function of
      mobile and/or transplanted cells, particularly immune cells and cellular
      therapeutics. (19)F MRI for cell tracking has several advantages; chief among
      them are its noninvasive nature which allows longitudinal data acquisition, use
      of a stable, non-radioactive isotope permitting long-term tracking, the absence
      of confounding endogenous signal, and the ability to quantify cell numbers from
      image data. However, generation of sufficient signal i.e. (19)F cell loading is a
      key challenge, particularly with non-phagocytic cells such as lymphocytes and
      stem cells. A range of (19)F cell labels have been developed, including
      emulsions, particles, polymers, and agents for clinical use. Various animal and
      primary human cells, such as dendritic cells, lymphocytes and phagocytes have
      been successfully labeled and studied in models of autoimmune disease,
      inflammation and transplant rejection. Primary human cells, particularly
      dendritic cells as used in vaccine therapy have been tested for imminent clinical
      application. Here, we summarize current cell loading strategies and sensitivity
      of in vivo cell imaging with (19)F MRI, and discuss the processing of image data
      for accurate quantification of cell numbers. This novel technology is uniquely
      applicable to the longitudinal and quantitative tracking of cells in vivo.

PMID- 22959181
TI  - Effect of orientation and density of nanotopography in dermal wound healing.
AB  - We report on the effect of synthetic extracellular matrix (ECM) scaffold in the
      form of uniformly-spaced nanogrooved surfaces in dermal wound healing. The rate
      of wound coverage was measured on various nanotopographical densities with
      vertical or parallel orientation using nanogrooves of 550 nm width with three
      different gaps of 550, 1100, and 2750 nm (spacing ratio: 1:1, 1:2 and 1:5).
      Guided by the nanotopographical cues in the absence of growth factors in wound
      healing process, the cultured NIH-3T3 cells demonstrated distinctly different
      migration speed, cell division, and ECM production as dictated by the
      topographical density and orientation, whereas the proliferation rate turned out
      to be nearly the same. Based on our experimental results, the nanopattern of 1:2
      spacing ratio yielded the best wound healing performance in terms of migration
      speed, which seems similar to the natural organization of collagen fibers.

PMID- 22959183
TI  - Tumor cells-specific targeting delivery achieved by A54 peptide functionalized
      polymeric micelles.
AB  - The delivery of all of administrated chemotherapeutics into tumor cells is an
      extreme object for tumor targeting therapy to enhance the curative effect and
      eliminate the side effect. However, until now, the targeting delivery has only
      partial been realized by passive targeting, which was called "enhanced
      permeability and retention" effect, and only few targeting delivery system was
      commercialized. Here, we designed and synthesized a hepatocarcinoma-binding
      peptide (A54 peptide, which was identified from a phage-display random peptide
      library) functionalized and PEGylated stearic acid grafted chitosan (A54-PEG-CS
      SA) micelles for targeting therapy of doxorubicin. The A54-PEG-CS-SA micelles
      presented special internalization ability into human hepatoma cells (BEL-7402)
      when the cells were co-incubated with normal liver cells in vitro, and high
      distribution ability to liver and hepatoma tissue in vivo. In vitro and in vivo
      anti-tumor activity results showed that A54-PEG-CS-SA micelles loading
      doxorubicin treatments suppressed tumor growth more effectively and reduced
      toxicity compared with commercial adriamycin injection.

PMID- 22959184
TI  - Multi-arm histidine copolymer for controlled release of insulin from poly(lactide
      co-glycolide) microsphere.
AB  - For long-term, sustained protein delivery, a new, star-shaped block copolymer
      composed of methoxy poly(ethylene glycol) (mPEG), branched oligoethylenimine
      (bOEI), and poly(l-histidine) (pHis) was synthesized via the multi-initiation and
      ring-opening polymerization (ROP) of His N-carboxy anhydride (NCA) on bOEI with a
      PEG conjugation. The resulting mPEG-bOEI-pHis (POH) had strong buffering capacity
      within the neutral-to-acidic pH range and was complexed with insulin (Ins) via an
      electrostatic attraction plus hydrophobic interactions, resulting in the
      formation of a dual-interaction complex (DIC, weight ratio 2) of approximately 30
      60 nm in size. This DIC tolerated high salt concentrations without
      destabilization, supporting the existence of hydrophobic interactions, and
      protected Ins from the organic solvent/water interface. The DIC in poly(lactide
      co-glycolide) microspheres (PLGA MS) as a long-term Ins delivery formulation was
      evenly distributed via a double-emulsion method. The DIC-loaded PLGA MS offered a
      higher Ins loading and a lower initial burst than Ins-loaded PLGA MS. This
      formulation possessed near zero-order release kinetics (for at least one month).
      In streptozotocin (STZ)-induced diabetic rats, a DIC-loaded PLGA MS formulation
      was able to maintain blood-glucose levels at 200-350 mg/dL for the first two
      weeks and even lower levels (100-200 mg/dL) for the next two weeks. Thus, a new
      POH polymer and its complex with a drug protein could have potential biological
      application as a long-term, sustained protein delivery system.

PMID- 22959185
TI  - Omission of surgery in elderly patients with early stage breast cancer.
AB  - AIM: To assess national trends over time in surgery for elderly patients with
      resectable breast cancer (BC) and to evaluate clinical outcome and cause of death
      after the omission of surgery in a regional cohort of elderly patients. METHODS:
      National trends in 1995-2005 were calculated using cancer registry data. In
      addition, a chart review was performed in a cohort of patients aged >= 75 years,
      with early stage BC but no primary surgery, diagnosed at five Dutch hospitals in
      1990-2005. Patient characteristics, comorbidity and reason for the omission of
      surgery were collected from the chart. Cause of death was retrieved from death
      certificate data registered at Statistics Netherlands. RESULTS: Omission of
      surgery increased significantly over time for patients aged 80 years and older
      (p<0.05). Of the 187 patients in the regional cohort (median age 85.9 years
      (range 75.0-97.7), 174 (92%) received hormonal therapy. Omission of surgery was
      at the patient's request in 59 patients (32%). Of the 178 patients that died
      during follow-up, 60 patients (34%) died of BC. For 81 patients (45%), BC was not
      clinically relevant at the time of death. Median overall survival was 2.3 years
      (range 0.2-10.7) and did not differ between BC and other causes of death (p=0.9).
      CONCLUSION: Omission of surgery for elderly patients with resectable BC has
      increased significantly over the past decade; instead patients often received
      primary endocrine treatment. Although this may appear an effective alternative to
      surgery, the potential for a longer term negative impact on disease control and
      quality of life deserves further investigation.

PMID- 22959186
TI  - Regorafenib for patients with previously untreated metastatic or unresectable
      renal-cell carcinoma: a single-group phase 2 trial.
AB  - BACKGROUND: Regorafenib inhibits VEGF receptors 1, 2, and 3 and PDGF receptors
      like other anti-angiogenic tyrosine-kinase inhibitors approved for treatment of
      advanced renal-cell cancer. Regorafenib also inhibits other potentially important
      angiogenic kinases like TIE2, activation of which is thought to be important in
      tumour escape mechanisms. This phase 2, open-label, non-randomised study assessed
      the safety and efficacy of the multikinase inhibitor regorafenib for treatment of
      renal-cell carcinoma. METHODS: Patients were recruited from 18 academic oncology
      centres across Europe and USA. Patients with previously untreated metastatic or
      unresectable clear-cell renal-cell carcinoma received oral regorafenib (160 mg
      per day) in repeating cycles of 3 weeks on, 1 week off until disease progression
      or until patients met the criteria for removal from study. The primary efficacy
      endpoint was the proportion of patients who achieved an objective overall
      response, assessed in all patients who were evaluable for response. The trial has
      finished. This trial is registered with ClinicalTrials.gov, number NCT00664326.
      FINDINGS: The study was done between April 30, 2008, and June 1, 2011. We
      screened 64 patients, of whom 49 received regorafenib. Median duration of
      treatment was 7.1 months (range 0.7-34.4, IQR 2.5-18.0) and at the time of data
      cutoff, six patients (12%) were still receiving treatment. 48 patients were
      assessable for tumour response. 19 patients (39.6%, 90% CI 27.7-52.5) had an
      objective response, all of which were partial responses. Drug-related adverse
      events occurred in 48 patients (98%) and drug-related serious adverse events in
      17 (35%). Grade 3 drug-related adverse events were common, most frequently hand
      and foot skin reaction (16 patients, 33%), diarrhoea (five patients, 10%), renal
      failure (five patients, 10%), fatigue (four patients, 8%), and hypertension
      (three patients, 6%). Two patients had grade 4 treatment-related adverse events:
      two cardiac ischaemia or infarction, one hypomagnesaemia, and one pain in the
      chest or thorax. Four patients died during study treatment or within 30 days of
      last dose, of which two were deemed likely to be related to the study drug.
      INTERPRETATION: Regorafenib has antitumour activity as first-line treatment for
      metastatic or unresectable renal-cell carcinoma. The drug's safety profile
      requires close monitoring.

PMID- 22959187
TI  - Choosing the right option for renal-cell carcinoma.

PMID- 22959188
TI  - beta-Glucan protects neutrophil extracellular traps against degradation by
      Aeromonas hydrophila in carp (Cyprinus carpio).
AB  - A novel host innate immune defence mechanism against invading pathogens, namely
      the formation of neutrophil extracellular traps (NETs), has recently been
      discovered. These NETs are described as DNA fibres released by dying neutrophils,
      which are able to entrap and kill various microbes. Here we studied the effect of
      the feed additive beta-glucan, namely MacroGard((r)), on the degradation of NETs
      by the important fish pathogen Aeromonas hydrophila. Therefore, common carp
      (Cyprinus carpio) head kidney cells consisting of approximately 45% neutrophils
      were isolated and treated with or without beta-glucan. The degradation of NETs
      after co-incubation with A. hydrophila was analysed by immunofluorescence
      microscopy. The data show that A. hydrophila is able to degrade NETs and that
      treatment of cells with beta-glucan significantly protects the NETs against
      bacterial degradation. Control experiments revealed that beta-glucan augments
      nuclease activity of the bacteria at the same time while protecting the NETs
      against its degradation. In conclusion the data indicate that beta-glucan might
      affect the composition and stabilisation of NETs and thereby protecting them
      against degradation by A. hydrophila nuclease.

PMID- 22959189
TI  - Dexamethasone treatment interferes with the pharmacokinetics of ivermectin in
      young cattle.
AB  - An experiment was carried out to study the possible interaction between
      dexamethasone (DXM) treatment and the efficacy of ivermectin (IVM) treatment in
      young cattle. Two groups, each of seven calves, were experimentally inoculated
      with an equal mixture containing 15,000 third stage larvae of Cooperia oncophora
      and Ostertagia ostertagi each, and with no history of being resistant to any
      anthelmintics. However, in this study C. oncophora was unexpectedly classified as
      IVM-resistant according to the outcome from the faecal egg count reduction test
      (FECRT). Blood parameters and faecal egg counts (FEC) were monitored from 0 to 35
      days post infection (d.p.i.). The calves in one group received intramuscular
      injections of short and long-term acting DXM at 22 and 24 d.p.i., respectively.
      The other group remained as a control. Three days post patency (24 d.p.i.) both
      groups were injected subcutaneously with IVM (Merial) at the recommended dose
      (0.2mg/kg). A significant difference (p<0.001) in FEC patterns was observed
      between groups. Although both groups still excreted eggs (100-200 eggs per gram
      faeces) 11 days post anthelmintic treatment, the control group had a
      significantly higher reduction between 23 and 35 d.p.i. (p=0.025). After 35 days,
      four animals per group were euthanized, and worms in the gastrointestinal tract
      were counted. No O. ostertagi were found in the abomasums, but low to high
      numbers (800-6200) of C. oncophora remained in the small intestines in both
      groups. Overall, these findings indicated that there was an interaction between
      the efficacy of IVM and DXM treatment. As significantly lower plasma levels of
      IVM were observed in the DXM group, we conclude that the impaired efficacy of
      ivermectin was most likely due to the altered pharmacokinetics.

PMID- 22959191
TI  - Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell
      carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) of renal cell carcinoma (RCC) is used
      to obtain local control of small renal masses. However, available long-term
      oncologic outcomes for RFA of RCC are limited by small numbers, short follow-up,
      and lack of pathologic diagnoses. OBJECTIVE: To assess the oncologic
      effectiveness of RFA for the treatment of biopsy-proven RCC. DESIGN, SETTING, AND
      PARTICIPANTS: Exclusion criteria included prior RCC or metastatic RCC, familial
      syndromes, or T2 RCC. We retrospectively reviewed long-term oncologic outcomes
      for 185 patients with sporadic T1 RCC. Median follow-up was 6.43 yr
      (interquartile range [IQR]: 5.3-7.7). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The chi-square test and Wilcoxon rank-sum tests were used to compare
      proportions and medians, respectively. Disease-specific survival and overall
      survival (OS) were calculated using Kaplan-Meier analysis, then stratified by
      tumor stage, and comparisons were made using log-rank analysis. The 5-yr disease
      free survival (DFS) and OS rates are reported. A p value <0.05 was considered
      statistically significant. RESULTS AND LIMITATIONS: Median tumor size was 3 cm
      (IQR: 2.1-3.9 cm). Tumor stage was T1a: 143 (77.3%) or T1b: 42 (22.7%). Twenty
      four patients (13%) were retreated for residual disease. There were 12 local
      recurrences (6.5%), 6 recurrences in T1a disease (4.2%) and 6 in T1b disease
      (14.3%) (p=0.0196). Median time to recurrence was 2.5 yr. Local salvage RFA was
      performed in six patients, of whom five remain disease free at 3.8-yr median
      follow-up. Tumor stage was the only significant predictor of DFS on multivariate
      analysis. At last follow-up, 164 patients (88.6%) were disease free (T1a: n=132
      [92.3%]; T1b: n=32 [76.2%]; p=0.0038). OS was similar regardless of stage
      (p=0.06). Five patients developed metachronous renal tumors (2.7%). Four patients
      developed extrarenal metastases (2.2%), three of whom died of metastatic RCC
      (1.6%). CONCLUSIONS: In poor surgical candidates, RFA results in durable local
      control and low risk of recurrence in T1a RCC. Higher stage correlates with a
      decreased disease-free survival. Long-term surveillance is necessary following
      RFA. Patient selection based on tumor characteristics, comorbid disease, and life
      expectancy is of paramount importance.

PMID- 22959192
TI  - Impact of age and comorbidities on long-term survival of patients with high-risk
      prostate cancer treated with radical prostatectomy: a multi-institutional
      competing-risks analysis.
AB  - BACKGROUND: Survival after surgical treatment using competing-risk analysis has
      been previously examined in patients with prostate cancer (PCa). However, the
      combined effect of age and comorbidities has not been assessed in patients with
      high-risk PCa who might have heterogeneous rates of competing mortality despite
      the presence of aggressive disease. OBJECTIVE: To examine the risk of 10-yr
      cancer-specific mortality (CSM) and other-cause mortality (OCM) according to
      clinical and pathologic characteristics of patients treated with radical
      prostatectomy (RP) for high-risk PCa. DESIGN, SETTING, AND PARTICIPANTS: Within a
      multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined
      as the presence of at least one of these risk factors: prostate-specific antigen
      >20 ng/ml, biopsy Gleason score 8-10, clinical stage >= T3) were identified.
      INTERVENTION: All patients underwent RP and pelvic lymph node dissection. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Competing-risk Poisson regression analyses
      were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The
      same analyses were also conducted after stratification of patients according to
      age at surgery, comorbidity status assessed by the Charlson Comorbidity Index
      (CCI), and number of risk factors (one vs two or more). RESULTS AND LIMITATIONS:
      Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes.
      The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%,
      respectively. Age and CCI were the major determinants of OCM; their impact on CSM
      was minimal. OCM was the leading cause of death in all patient groups except in
      young men (<= 59 yr) with no comorbidities, regardless of the number of risk
      factors (10-yr CSM and OCM 6.9-12.8% and 5.5-6.3%, respectively). The main
      limitation was the lack of patients managed conservatively. CONCLUSIONS: Even in
      the context of high-risk PCa, long-term CSM after RP is modest and represents the
      leading cause of death only in young, healthy patients. Conversely, older and
      sicker patients with multiple risk factors are at the highest risk of dying from
      OCM while sharing very low CSM rates.

PMID- 22959193
TI  - A study of user requests regarding the fully electronic health record system at
      Seoul National University Bundang Hospital: challenges for future electronic
      health record systems.
AB  - OBJECTIVE: Although the adoption rates for Electronic Health Records (EHRs) are
      growing, significant opportunities for further advances in EHR system design
      remain. The goal of this study was to identify issues that should be considered
      in the design process for the successful development of future systems by
      analyzing end users' service requests gathered during a recent three-year period
      after a comprehensive EHR system was implemented at Seoul National University's
      Bundang Hospital in South Korea. METHODS: Data on 11,400 service requests from
      end users of the EHR system made from 2008 through 2010 were used in this study.
      The requests were categorized as program modification/development, data request,
      insurance-fee identification/generation, patient-record merging, or other. The
      authors further subcategorized the requests for program modification/development
      into the following nine areas of concern: (1) indicators and statistics, (2)
      patient safety and quality of care, (3) special task-oriented functionalities,
      (4) ease of use and user interface, (5) system speed, (6) interoperability and
      integration, (7) privacy and security, (8) customer service, and (9)
      miscellaneous. The system users were divided into four groups--direct care, care
      support, administrative/insurance, and general management--to identify each
      group's needs and concerns. RESULTS: The service requests for program
      modification/development, data request, insurance-fee identification/generation,
      patient-record merging, and other issues constituted approximately 49.2%, 33.9%,
      11.4%, 4.0%, and 1.5% of the total data set, respectively. The number of data
      request service requests grew over the three years studied. Different groups of
      users were found to have different concerns according to their activities and
      tasks. Within the program-modification/development category, end users were most
      frequently concerned with ease of use and user interface (38.1% of the total) and
      special task-oriented functionalities (29.3% of the total) in their use of the
      EHR system, with increasing numbers of requests in both categories over the three
      years. Users in the direct-care group differed from the other groups in that they
      most frequently submitted requests related to ease of use and user interface,
      followed by special functionalities, patient safety and quality care, and
      customer service, while users in other groups submitted requests concerning ease
      of use and user interface and special functionalities with a similarly high
      frequency. CONCLUSIONS: Users have continued to make suggestions about their
      needs and requirements, and the EHR system has evolved to optimize ease of use
      and special functionalities for particular groups of users and particular
      subspecialties. Based on our experiences and the lessons we have learned in the
      course of maintaining full-EHR systems, we suggest that the key goals to be
      considered for future EHR systems include innovative new user-interface
      technologies; special extended functions for each user group's specific task
      oriented requirements; powerful, easy-to-use functions to support research; new
      flexible system architecture; and patient-directed functions.

PMID- 22959194
TI  - Editorial process in Europe.

PMID- 22959195
TI  - Anterior capsulolabral reconstruction of the shoulder in athletes.
AB  - We did an anterior capsulolabral reconstruction for recurrent subluxation or
      dislocation of the shoulder in 75 athletes after failure of conservative therapy.
      Average follow-up was 39 months (range 28 to 60 months). The results were 77%
      excellent, 75% good, 3% fair, and 5% poor. Seventy-five percent of the
      professional and 100% of the college baseball players returned to their previous
      level of competition. Seventy-seven percent of the professional pitchers were
      able to return to professional pitching. The range of motion at follow-up was
      full in 79% of the athletes. No infections or nerve injuries occurred. The
      anterior capsulolabral reconstruction procedure combined with an early
      rehabilitation program appears to provide an improved outcome compared with
      previously reported procedures for anterior instability of the shoulder in
      athletes.

PMID- 22959196
TI  - Impingement of the deep surface of the supraspinatus tendon on the
      posterosuperior glenoid rim: An arthroscopic study.
AB  - Seventeen athletes presenting with unexplained shoulder pain on throwing
      underwent arthroscopic examination. All but one practiced a throwing sport. The
      dominant arm was involved in all patients except one bodybuilder. Their mean age
      was 25 years (range 15 to 30 years), and they had symptoms present for a mean of
      27 months. None had clinical, radiologic, or arthroscopic evidence of anterior
      instability. Preoperative clinical examination typically revealed localized pain
      on full external rotation and 90 degrees  abduction, signs of rupture of the
      rotator cuff, and positive impingement sign. In 10 cases computed tomographic
      arthrogram showed evidence of abnormality at the posterior edge of the glenoid.
      The mean humeral retrotorsion was 10 degrees  (range 5 degrees  to 30 degrees ).
      Under arthroscopy, with the arm placed in full external rotation and 90 degrees 
      abduction (the throwing position), impingement was found between the
      posterosuperior border of the glenoid and the undersurface of the tendinous
      insertions of supraspinatus and infraspinatus. A partial rupture of the cuff,
      which was demonstrated by arthrogram, was confirmed in eight patients, whereas a
      partial capsulotendinous rupture, which was not demonstrated by arthrogram, was
      seen in nine patients. Twelve patients had further lesions of the posterosuperior
      labrum. This study suggests that in addition to Neer's "impingement syndrome" and
      Jobe's "instability with secondary impingement," impingement of the undersurface
      of the cuff on the posterosuperior glenoid labrum may be a cause of painful
      structural disease of the shoulder in the thrower.

PMID- 22959197
TI  - Use of a thirty-degree caudal tilt radiograph in the shoulder impingement
      syndrome.
AB  - The formation of a bony spur or prominence at the anterior acromion is an
      important pathologic factor in impingement syndrome, and the detection and
      estimation of the size of such a spur are also important for diagnosis and
      treatment. We investigated the usefulness of a 30 degrees  caudal tilt view of
      the shoulder for detection of the bony spur. A 30 degrees  caudal tilt view was
      used to detect a spur in 52 of 73 joints diagnosed as having the impingement
      syndrome, whereas the spur was detected in only 27 joints when routine
      anteroposterior films were used. Only sufficiently larger spurs that projected
      toward the coracoid process could be recognized on anteroposterior films. Because
      the 30 degrees  caudal tilt view demonstrated the exact architecture of the spur
      encountered at operation, it was useful not only for preoperative planning but
      also for evaluation of the adequacy of surgery.

PMID- 22959198
TI  - A new strategy for treatment of suprascapular entrapment neuropathy in athletes:
      Shaving of the base of the scapular spine.
AB  - A study of three volleyball teams comprising 40 players demonstrated the frequent
      occurrence of infraspinatus muscle atrophy. Anatomic studies of the suprascapular
      nerve in 20 cadavers revealed the possibility of entrapment of the nerve at the
      spinoglenoid notch. Four athletes with suprascapular neuropathy were followed up
      after surgical treatment. Shaving of the lateral edge of the base of the scapular
      spine proved effective. However, it is suggested that preventive measures such as
      strengthening of the infraspinatus muscle are important because suprascapular
      neuropathy in athletes is combined to at least some degree with damage to the
      muscle itself.

PMID- 22959199
TI  - Finite element modeling of the glenoid component: Effect of design parameters on
      stress distribution.
AB  - A two-dimensional plane stress model of the natural glenoid was developed with
      finite element analysis to observe the stress distributions under various loading
      conditions. Different glenoid prosthetic designs were evaluated with the use of
      the finite element model in an attempt to elucidate key features for an improved
      design. These included a keel model, a stair-stepped model, and a wedge model. In
      addition to the evaluation of these designs, different interfaces were introduced
      to simulate various environments of the prostheses, and different material
      combinations were studied. Based on the finite element analysis, the following
      design parameters were found to be important: (1) an all-polyethylene implant
      appears to provide a more physiologic stress distribution for nonaxial loads if
      no soft tissue is present; (2) the presence of a soft-tissue layer causes higher
      stresses; (3) the stair-stepped and wedge models produced a more natural stress
      distribution compared with the keel design; and (4) screw orientation was not a
      significant design parameter.

PMID- 22959200
TI  - Stabilizers of capitellocondylar total elbow arthroplasty.
AB  - The contribution of the medial and lateral collateral ligaments (MCL, LCL) and
      muscle forces to the kinematics and stability of the capitellocondylar total
      elbow arthroplasty was investigated in six fresh cadaveric elbows. The three
      dimensional orientation of the ulna relative to the humerus was monitored with
      the use of an electromagnetic tracking device in neutral, valgus, and varus
      stress positions with (1) the ligaments intact, (2) LCL insufficiency obtained by
      osteotomizing the lateral epicondyle, (3) partial MCL insufficiency obtained by
      sectioning either the anterior or posterior bundle of the MCL, and (4) complete
      MCL insufficiency. Simulated muscle forces were applied as follows: (1) no load,
      (2) 1 kg each to the biceps and the brachialis and 2 kg to the triceps, and (3) 2
      kg to the biceps and the brachialis and 4 kg to the triceps. The laxity was
      defined as the difference in valgus/varus orientation of the ulna in the valgus
      and varus stress positions. The laxity at 40 degrees , 75 degrees , and 110
      degrees  elbow flexion was analyzed. The greatest laxity occurred with LCL
      insufficiency (40.7 degrees  +/- 11.6 degrees , average at three flexion angles)
      followed by that with MCL insufficiency (15.7 degrees  +/- 9.9 degrees ), both of
      which were significantly larger than laxity with the intact ligaments (5.6
      degrees  +/- 2.5 degrees ). The laxity with the anterior bundle sectioned (12.0
      degrees  +/- 8.1 degrees ) was significantly greater than with the posterior
      bundle sectioned (3.3 degrees  +/- 3.6 degrees ); thus the contribution of
      anterior bundle to stability was four times that of posterior bundle. Stabilizing
      effect of muscle loading was small in elbows with intact ligaments, whereas it
      was large with LCL or MCL insufficiency. Based on these data, we can see that the
      integrity of both the MCL and LCL is essential to maintain stability of this
      total elbow, the anterior bundle is a more important stabilizer than the
      posterior bundle, and the collateral ligaments seem to be the primary stabilizer
      and the musculature seems to be the secondary stabilizer. Careful implantation
      technique to preserve the collateral ligaments is required to obtain
      postoperative stability of this arthroplasty. Otherwise, routine exposure of the
      MCL and repair or reinforcement of the MCL, if deficient, may need to be
      considered during surgery.

PMID- 22959201
TI  - Alfred R. Shands, Jr., Lecture: The shoulder-an explosion of interest in North
      America.

PMID- 22959202
TI  - Childhood and family influences on depression, chronic physical conditions, and
      their comorbidity: findings from the Ontario Child Health Study.
AB  - BACKGROUND: Previous research has shown that various childhood risk factors are
      related to depression and chronic physical conditions (CPCs) later in life.
      However, little is known about risk factors associated with comorbidity for these
      conditions. The purpose of this study was to examine the association between
      individual (school performance, childhood physical and sexual abuse) and family
      risk variables (socioeconomic status, parental mental health, medical condition,
      and functional limitation) with depression only, chronic pain conditions (back
      pain and headaches) or other CPCs (respiratory, cardiovascular and digestive
      disorders, and diabetes) and the comorbidity of either CPC category with
      depression assessed in early adulthood. METHODS: We used data from the Ontario
      Child Health Study, a prospective, population-based study of 3294 children (ages
      4-16) enrolled in 1983 and meeting inclusion criteria at follow-up in 2001 (N =
      1475; ages 21-35 years). RESULTS: Using multinomial logistic regression models,
      controlling for sex and age, childhood history of physical abuse was associated
      with most outcomes (OR = 1.86, 95% confidence interval [CI] 1.16-2.97 to 4.36,
      95% CI, 1.74-10.97). Parental mental health, childhood functional limitation,
      childhood history of sexual abuse and family functioning were all related to
      comorbid depression and chronic pain conditions. Parental mental health was also
      related to increased risk of other CPCs (ORs = 1.66; 95% CI, 1.08-2.55).
      CONCLUSION: We found that the greatest disease risk (comorbid depression and
      chronic pain conditions) was related to the greatest number of childhood risk
      factors. Although there was some evidence of specificity, there was overlap in
      childhood physical abuse predicting almost all outcomes. Efforts targeting the
      prevention and treatment of childhood maltreatment are critical in order to
      prevent the long lasting impact of childhood adversity on mental and physical
      outcomes in early adulthood.

PMID- 22959203
TI  - Mutual enhancement of the current density and the coulombic efficiency for a
      bioanode by entrapping bi-enzymes with Os-complex modified electrodeposition
      paints.
AB  - A bioanode with high current density and coulombic efficiency was developed by co
      immobilization of pyranose dehydrogenase from Agaricus meleagris (AmPDH) with the
      dehydrogenase domain of cellobiose dehydrogenase from Corynascus thermophiles
      (recDHCtCDH) expressed recombinantly in Escherichia coli. The two enzymes were
      entrapped in Os-complex modified electrodeposition polymers (Os-EDPs) with
      specifically adapted redox potential by means of chemical co-deposition. AmPDH
      oxidizes glucose at both the C2 and C3 positions whereas recDHCtCDH oxidizes
      glucose only at the C1 position. Electrochemical measurements reveal that
      maximally 6 electrons can be harvested from one glucose molecule at the two
      enzyme anode via a cascade reaction, as AmPDH oxidizes the products formed from
      of the recDHCtCDH catalyzed substrate oxidation and vice versa. Furthermore, a
      significant increase in current density can be obtained by combining AmPDH and
      recDHCtCDH in a single modified electrode. We propose the use of this bioanode in
      biofuel cells with increased current density and coulombic efficiency.

PMID- 22959204
TI  - An ultrasensitive label-free biosensor for assaying of sequence-specific DNA
      binding protein based on amplifying fluorescent conjugated polymer.
AB  - Sensitive, reliable, and simple detection of sequence-specific DNA-binding
      proteins (DBP) is of paramount importance in the area of proteomics, genomics,
      and biomedicine. We describe herein a novel fluorescent-amplified strategy for
      ultrasensitive, visual, quantitative, and "turn-on" detection of DBP. A Forster
      resonance energy transfer (FRET) assay utilizing a cationic conjugated polymer
      (CCP) and an intercalating dye was designed to detect a key transcription factor,
      nuclear factor-kappa B (NF-kappaB), the model target. A series of label-free DNA
      probes bearing one or two protein-binding sites (PBS) were used to identify the
      target protein specifically. The binding DBP protects the probe from digestion by
      exonuclease III, resulting in high efficient FRET due to the high affinity
      between the intercalating dye and duplex DNA, as well as strong electrostatic
      interactions between the CCP and DNA probe. By using label-free hairpin DNA or
      double-stranded DNA containing two PBS as probe, we could detect as low as 1
      pg/MUL of NF-kappaB in HeLa nuclear extracts, which is 10000-fold more sensitive
      than the previously reported methods. The approach also allows naked-eye
      detection by observing fluorescent color of solutions with the assistance of a
      hand-held UV lamp. Additionally, a less than 10% relative standard deviation was
      obtained, which offers a new platform for superior precision, low-cost, and
      simple detection of DBP. The features of our optical biosensor shows promising
      potential for early diagnosis of many diseases and high-throughput screening of
      new drugs targeted to DNA-binding proteins.

PMID- 22959205
TI  - Synthesis and biological evaluation of cyanoguanidine derivatives of loratadine.
AB  - Cyanoguanidine derivatives of loratadine (3a-i) were synthesized and screened for
      antitumor and anti-inflammatory activity. The most promising compound 3c (R=n
      C(8)H(17)) possessed at least twofold higher in vitro cytotoxicity than 5
      fluorouracil against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29)
      carcinoma cells. The mode of action, however, is so far unclear. The
      participation of the COX-1/2 enzymes on the cytotoxicity, however, is very
      unlikely. Nevertheless all compounds showed stronger in vivo anti-inflammatory
      activity than ibuprofen in the xylene-induced ear swelling assay in mice.

PMID- 22959206
TI  - Design, synthesis and identification of a new class of triarylmethyl amine
      compounds as inhibitors of apolipoprotein E production.
AB  - We have identified a new class of triarylmethyl amine compounds that can inhibit
      apolipoprotein E (apoE) production. ApoE is a cholesterol- and lipid-carrier
      protein implicated in aging, atherosclerosis, Alzheimer's Disease (AD), and other
      neurological and lipid-related disorders. Attenuation of apoE production is
      generally considered to be of therapeutic value. A majority of the apoE in the
      brain is produced by astrocytes. Here, we describe the design, synthesis, and
      biological screening of a small library of compounds that led to the
      identification of four triarylmethyl amines as potent inhibitors of apoE
      production in CCF-STTG1 astrocytoma cells.

PMID- 22959207
TI  - An efficient one-pot synthesis and photoinduced DNA cleavage studies of 2-chloro
      3-(5-aryl-4,5-dihydroisoxazol-3-yl)quinolines.
AB  - 4,5-Dihydroisoxazoles continue to attract considerable interest due to their wide
      spread biological activities. Here, we identify an efficient protocol for the
      preparation of 4,5-dihydroisoxazoles (2-isaxazolines) (4a-g) from quinolinyl
      chalcones. The nucleolytic activities of synthesized compounds were investigated
      by agarose gel electrophoresis. All these compounds were showed the remarkable
      DNA cleavage activity (concentration dependent) with pUC19 DNA at 365nm UV light.
      The DNA cleavage activity was significantly enhanced by the presence of iminyl
      and carboxy radicals of DIQ.

PMID- 22959208
TI  - The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory
      cytokine expression in the hippocampus in aged rats.
AB  - BACKGROUND: Neuroinflammatory response triggered by surgery has been increasingly
      reported to be associated with postoperative cognitive dysfunction.
      Proinflammatory cytokines, such as interleukin 1beta (IL-1beta) and tumor
      necrosis factor alpha (TNF-alpha), play a pivotal role in mediating surgery
      induced neuroinflammation. The role of cyclooxygenase-2 (COX-2), a critical
      regulator in inflammatory response, in surgery-induced neuroinflammation is still
      unknown. The aim of the study was to investigate the changes of COX-2 expression
      and prostaglandin E2 (PGE2) production in the hippocampus in aged rats following
      partial hepatectomy. The effects of selective COX-2 inhibitor (parecoxib) on
      hippocampal proinflammatory cytokine expression were also evaluated. METHODS:
      Aged rats were randomly divided into three groups: control (n = 10), surgery (n =
      30), and parecoxib (n = 30). Control animals received sterile saline to control
      for the effects of injection stress. Rats in the surgery group received partial
      hepatectomy under isoflurane anesthesia and sterile saline injection. Rats in the
      parecoxib group received surgery and anesthesia similar to surgery group rats,
      and parecoxib treatment. On postanesthetic days 1, 3, and 7, animals were
      euthanized to assess levels of hippocampal COX-2 expression, PGE2 production, and
      cytokines IL-1beta and TNF-alpha expression. The effects of parecoxib on
      proinflammatory cytokine expression were also assessed. RESULTS: Partial
      hepatectomy significantly increased COX-2 expression, PGE2 production, and
      proinflammatory cytokine expression in the hippocampus in aged rats on
      postoperative days 1 and 3. Parecoxib inhibited hippocampal IL-1beta and TNF
      alpha expression through downregulation of the COX-2/PGE2 pathway. CONCLUSION:
      COX-2 may play a critical role in surgery-induced neuroinflammation. The COX-2
      inhibitor may be a promising candidate for treatment of neuroinflammation caused
      by surgical trauma.

PMID- 22959209
TI  - Hypoxia enhances colon cancer migration and invasion through promotion of
      epithelial-mesenchymal transition.
AB  - BACKGROUND: A hypoxic environment exists in most solid tumors because in rapidly
      growing tumors, the development of angiogenic vasculature is heterogenous,
      usually not enough to overcome the necessary oxygen supply. In an ischemic
      condition, cancer cells develop escape mechanisms to survive and leave the
      unfavorable environment. That result in the acquisition of increased potential
      for local invasion and evasion to distant organs. However, the escape mechanisms
      of cancer cells from hypoxic stress have not been fully characterized. MATERIALS
      AND METHODS: The human colon cancer cell line LoVo was cultured in hypoxia, and
      the adhesive and migratory properties were analyzed. The expression of cell
      surface and cytoplasmic molecules was also investigated. RESULTS: Under hypoxic
      conditions, cells developed epithelial-mesenchymal transition. The expression
      levels of alpha2, alpha5, and beta1 integrins were significantly upregulated and,
      as a consequence, the ability to adhere to and migrate on collagen and
      fibronectin was increased. On the other hand, the expression of 67-kDa laminin
      receptor and the abilities to adhere to and migrate on laminin were decreased.
      Additionally, the expression of CXCR4 was significantly increased on cells
      cultured in hypoxia, and the chemotactic activity to stromal cell-derived factor
      1alpha was remarkably increased. CONCLUSIONS: Hypoxic stress induced active
      epithelial-mesenchymal transition in colon cancer cells, with the typical
      morphologic and functional changes. These morphologic and functional changes of
      beta1 integrins, the 67-kDa laminin receptor, and CXCR4 may be essential for the
      acquisition of the invasive and metastatic features in colorectal cancer.

PMID- 22959210
TI  - Vein graft harvesting--handle with care.

PMID- 22959211
TI  - Commentary: 17-beta-estradiol reappropriates mass lost to the hypermetabolic
      state in thermally injured rats.

PMID- 22959212
TI  - How reliable and accurate is indocyanine green video angiography in the
      evaluation of aneurysm obliteration?
AB  - INTRODUCTION: Indocyanine green video angiography (ICG-VA) has been recently
      introduced into neurovascular surgery and gained a role in assessing vessel
      patency and obliteration of intracranial aneurysms (IA) after clipping. Although
      its correlation with intra-postoperative angiography was demonstrated in previous
      studies, difficulties in evaluating aneurysm obliteration have not been reported.
      We report reliability and accuracy of ICG-VA in 109 clipped aneurysms with
      attention given to five cases in which ICG-VA evaluation resulted in false
      indication that aneurysms were secure in terms of complete obliteration.
      MATERIALS AND METHODS: A retrospective chart review was performed of IAs
      surgically treated by a single surgeon from January 2009. In all cases, aneurysm
      obliteration was confirmed by a combination of microdoppler ultrasonography
      (MUSG), ICG-VA, and post-operative angiography. RESULTS: ICG-VA appropriately
      assessed vessel patency and aneurysm obliteration in 93.5% of aneurysms clipped.
      In four cases (3.6%), puncturing the dome of the aneurysm after satisfactory
      clipping revealed persistent flow within the aneurysm despite ICG-VA showing no
      flow after clipping. In one case (0.9%), ICG-VA showed persistent flow within the
      aneurysm and MUSG did not, and puncture of the dome confirmed no flow within the
      aneurysm. In one case (0.9%), ICG-VA failed to demonstrate residual neck.
      CONCLUSION: ICG-VA is a simple and safe procedure and an important adjunct to
      microsurgical clipping of aneurysm. Although ICG-VA assesses vessel patency and
      obliteration of aneurysms in most cases, applying the principles of microsurgery
      in aneurysm clipping remains a main tool for obtaining the complete obliteration
      of aneurysm along with preservation of the normal vasculature.

PMID- 22959213
TI  - Intramedullary thoracic spine epidermoid cyst with myelopathic presentations: a
      report of a rare case.

PMID- 22959214
TI  - The impact of repeated surgery and adjuvant therapy on survival for patients with
      recurrent glioblastoma.
AB  - OBJECTIVE: Treatment of glioblastoma recurrence can have a palliative aim, after
      considering risks and potential benefits. The aim of this study is to verify the
      impact of surgery and of palliative adjuvant treatments on survival after
      recurrence. METHODS: From January 2002 to June 2008, we treated 76 consecutive
      patients with recurrent glioblastoma. Treatment was: 1-surgery alone--17
      patients; 2-adjuvant-therapy alone--24 patients; 3-surgery and adjuvant therapy-
      16 patients; no treatment--19 patients. The impact on median overall-survival (OS
      time between recurrence and death/last follow-up) of age, Karnofsky performance
      scale (KPS), resection extent and adjuvant treatment scheme (Temozolomide alone
      vs low-dose fractionated radiotherapy vs others) was determined. Survival curves
      were obtained through the Kaplan-Meier method. Cox proportional-hazards was used
      for multivariate analyses. Significance was set at p<0.05. RESULTS: Median OS was
      7 months. At univariate analysis, patients with a KPS>=70 had a longer OS (9
      months vs 5 months--p<0.0001). OS was 6 months for patients treated with surgery
      alone, 5 months for patients that received no treatment, 8 months for patients
      treated with chemotherapy alone, 14 months for patients treated with surgery and
      adjuvant therapy--p=0.01. Patients with a KPS<70 were significantly at risk for
      death - HR 2.8 - p=0.001. Subgroup analysis showed no significant differences
      between patients receiving gross total or partial tumor resection and among
      patients receiving different adjuvant therapy schemes. Major surgical morbidity
      at tumor recurrence occurred in 16 out of 33 patients (48%). CONCLUSION: It is
      fundamental, before deciding to operate patients for recurrence, to carefully
      consider the impact of surgical morbidity on outcome.

PMID- 22959215
TI  - Merkel-cell polyomavirus (MCPyV) is rarely associated to B-chronic lymphocytic
      leukemia (1 out of 50) samples and occurs late in the natural history of the
      disease.
AB  - BACKGROUND: Previous studies have reported conflicting results on the frequency
      and potential pathogenetic role of Merkel-cell polyomavirus (MCPyV) in B-chronic
      lymphocytic leukemia (B-CLL). OBJECTIVES: To evaluate the association of MCPyV to
      B-CLL and to investigate the occurrence of MCPyV infection in relationship to the
      natural history of B-CLL. STUDY DESIGN: Samples of primary B-CLL peripheral blood
      mononuclear cells were obtained from two distinct University Hospitals of Italy
      from January 2010. For one B-CLL patient, it was possible to retrospectively
      examine the blood sample at diagnosis of B-CLL (March 2004) and several
      pathological tissues of cutaneous tumors occurring during the course of the
      disease. RESULTS: Only one out of 50 B-CLL blood samples examined was positive
      for MCPyV DNA. Retrospective analysis revealed that MCPyV DNA was absent in
      peripheral blood sample at diagnosis, becoming present only in advanced disease
      stages also in tonsil tissue as well as in a biopsy of differentiated squamous
      cell carcinoma. CONCLUSIONS: The association with MCPyV seems to represent a rare
      and late event during the natural history of B-CLL.

PMID- 22959216
TI  - Tobacco mosaic virus in cigarettes and saliva of smokers.
AB  - BACKGROUND: Tobacco mosaic virus (TMV) has been described as viable in cigarettes
      or cigar tobacco. It has been cultured about 50 years ago from sputa and
      thoracentesis fluids of cigarette smokers with a history of pulmonary disease and
      from lung cancerous matter. In addition, TMV RNA has been recovered recently from
      human stools while tobacco DNA was recovered from smokers' bronchoalveolar
      lavages. OBJECTIVES: We assessed the prevalence, titers, and infectivity of TMV
      in tobacco cigarettes and in the saliva of smokers and non smokers. STUDY DESIGN:
      Tobacco cigarettes from 10 packs of different brands were purchased. Saliva was
      collected from 12 smokers and 15 non-smokers. Cigarettes and saliva samples were
      tested for the presence of TMV RNA using a home-made quantitative real-time RT
      PCR assay. TMV RNA quantification was enabled by using dilutions of purified TMV.
      TMV viability was tested by inoculating leaves of Nicotiana tabacum Xanthi (NtX).
      RESULTS: All 47 smoking cigarettes of six brands were TMV RNA-positive (mean
      titer, 9.5 log(10)copies/cigarette); TMV was found viable in 53% of them. In
      addition, 20/44 (45%) saliva from 12 smokers compared to 0/16 saliva from 15 non
      smokers tested positive for TMV RNA (mean titer, 3.8 log(10)copies/ml) (p=0.001).
      CONCLUSIONS: Our results indicate that the TMV genome may get access to the human
      body by direct exposure through smoking. Although plant viruses are considered
      not pathogenic for animals, these data prompt to study if TMV RNA is present and
      induces a modification of the transcriptional program in lung cells of cigarette
      smokers.

PMID- 22959218
TI  - Ginkgo and AD: key negatives and lessons from GuidAge.

PMID- 22959219
TI  - Resynchronization therapy for right ventricular failure: restoring harmony in
      left ventricular contractility.

PMID- 22959217
TI  - Long-term use of standardised Ginkgo biloba extract for the prevention of
      Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.
AB  - BACKGROUND: Prevention strategies are urgently needed to tackle the growing
      burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of
      standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's
      disease in elderly adults with memory complaints. METHODS: In the randomised,
      parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we
      enrolled adults aged 70 years or older who spontaneously reported memory
      complaints to their primary-care physician in France. We randomly allocated
      participants in a 1:1 ratio according to a computer-generated sequence to a twice
      per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched
      placebo. Participants and study investigators and personnel were masked to study
      group assignment. Participants were followed-up for 5 years by primary-care
      physicians and in expert memory centres. The primary outcome was conversion to
      probable Alzheimer's disease in participants who received at least one dose of
      study drug or placebo, compared by use of the log-rank test. This study is
      registered with ClinicalTrials.gov, number NCT00276510. FINDINGS: Between March,
      2002, and November, 2004, we enrolled and randomly allocated 2854 participants,
      of whom 1406 received at least one dose of ginkgo biloba extract and 1414
      received at least one dose of placebo. By 5 years, 61 participants in the ginkgo
      group had been diagnosed with probable Alzheimer's disease (1.2 cases per 100
      person-years) compared with 73 participants in the placebo group (1.4 cases per
      100 person-years; hazard ratio [HR] 0.84, 95% CI 0.60-1.18; p=0.306), but the
      risk was not proportional over time. Incidence of adverse events was much the
      same between groups. 76 participants in the ginkgo group died compared with 82
      participants in the placebo group (0.94, 0.69-1.28; p=0.68). 65 participants in
      the ginkgo group had a stroke compared with 60 participants in the placebo group
      (risk ratio 1.12, 95% CI 0.77-1.63; p=0.57). Incidence of other haemorrhagic or
      cardiovascular events also did not differ between groups. INTERPRETATION: Long
      term use of standardised ginkgo biloba extract in this trial did not reduce the
      risk of progression to Alzheimer's disease compared with placebo. FUNDING: Ipsen.

PMID- 22959220
TI  - Modified technique using allograft-prosthetic composite in the distal femur after
      bone tumor resection.
AB  - BACKGROUND: The purpose of this retrospective study was to analyze the results of
      treatment of bone tumor resection of the distal femur with the modified technique
      of allograft-prosthetic composite. METHODS: Twelve patients with distal femoral
      bone tumors were treated with deep-frozen cortical allograft struts and allograft
      prosthesis composites. There were five males and seven females with a median age
      of 29.5y. The minimum follow-up time was 12mo (median, 45.7mo; range, 12-81mo).
      Diagnoses included osteosarcoma in five patients, chondrosarcoma in three
      patients, giant cell tumors in three patients, and malignant fibrous histiocytoma
      in one patient. Five osteosarcoma patients were treated with adjuvant
      chemotherapy. RESULTS: At the latest follow-up examination, 11 patients were
      alive with no evidence of disease, and the limb was preserved in nine patients.
      One patient died of pulmonary metastases with no evidence of local recurrence.
      Seven healed without complications. A surgical procedure was performed in four
      patients because of complications, which included a fracture (one patient), deep
      infection (one patient), instability (one patient), and local recurrence (one
      patient). CONCLUSION: The modified technique of allograft-prosthetic composite is
      an effective treatment for bone tumor resection of the distal femur. This
      technique has many advantages, including augmentation of the bone stock,
      minimizing the risk of allograft fracture and nonunion, and decreasing the need
      for revision operations.

PMID- 22959221
TI  - Midterm outcomes in patients with cam femoroacetabular impingement treated
      arthroscopically.
AB  - PURPOSE: The purpose of this study was to evaluate the midterm outcomes of
      patients with cam-type femoroacetabular impingement treated arthroscopically.
      METHODS: Outcomes were measured with the Nonarthritic Hip Score (NAHS), visual
      analog scale pain scores, and satisfaction levels preoperatively; at 6 weeks and
      3, 6, 12, and 24 months postoperatively; and at final follow-up. Two hundred one
      procedures were available for final assessment with a minimum follow-up of 36
      months (mean, 46 months). Ninety-nine percent of hips had a preoperative Tonnis
      grade of 1 or less. RESULTS: The NAHS significantly improved from a mean of 56.1
      to 78.2 (P < .001). Visual analog scale pain scores improved from a mean of 6.8
      to 2.7 (P < .001). Preoperative to postoperative satisfaction levels improved
      from 0.5% to 75% of procedures. Twelve patients required hip arthroplasty during
      the follow-up period and had a higher incidence of grade 4 acetabular chondral
      defects versus those without arthroplasty (P < .03). Patients with pincer
      resections had significantly poorer results versus the remainder of the cohort (P
      < .01). CONCLUSIONS: We have shown satisfactory results using a validated hip
      scoring system, showing improvement in NAHS, pain scores, and satisfaction levels
      in a large cohort of patients with cam-type femoroacetabular impingement followed
      up for a mean of 46 months. The results have shown improvement and stability
      throughout a range of 36 to 70 months' follow-up. There was no difference in
      preoperative to postoperative NAHS between age groups. There was a larger
      percentage of grade 4 acetabular chondral defects in those patients who needed
      conversion to hip arthroplasty. Patients with associated pincer pathology had
      poorer results after acetabular rim resection. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 22959222
TI  - Does bilingualism twist your tongue?
AB  - The current study investigated whether bilingualism affects the processing of sub
      lexical representations specifying the sound structure of words. Spanish-English
      bilinguals, Mandarin-English bilinguals, and English-only monolinguals repeated
      English tongue twisters. Twister materials had word or nonword targets (thus
      varying in whether lexical information did or did not support sound processing),
      and similar or dissimilar sounds (thus varying in difficulty with respect to
      competition at a sub-lexical level). Even though bilinguals had learned English
      at an early age, and spoke English without an accent, Spanish-English bilinguals
      produced significantly more twister errors than monolinguals, particularly in the
      absence of lexical support. Mandarin-English bilinguals were also disadvantaged,
      but more consistently across all twister types. These results reveal that
      bilingual disadvantages extend beyond the lexical level to affect the processing
      of sub-lexical representations. More generally, these findings suggest that
      experience with sound structures (and not simply their intrinsic complexity)
      shapes sub-lexical processing for all speakers.

PMID- 22959223
TI  - Elucidation of the biosynthesis of the di-C-glycosylflavone isoschaftoside, an
      allelopathic component from Desmodium spp. that inhibits Striga spp. development.
AB  - Isoschaftoside, an allelopathic di-C-glycosylflavone from Desmodium spp. root
      exudates, is biosynthesised through sequential glucosylation and arabinosylation
      of 2-hydroxynaringenin with UDP-glucose and UDP-arabinose. Complete conversion to
      the flavone requires chemical dehydration implying a dehydratase enzyme has a
      role in vivo to complete the biosynthesis. The C-glucosyltransferase has been
      partially characterised and its activity demonstrated in highly purified
      fractions.

PMID- 22959224
TI  - Oleanane saponins from Bellis sylvestris Cyr. and evaluation of their
      phytotoxicity on Aegilops geniculata Roth.
AB  - Six oleanane saponins were isolated for the first time from leaves of Bellis
      sylvestris Cyr., the southern daisy. Their structures were established by the
      extensive use of 2D-NMR experiments, including COSY, TOCSY, NOESY, HSQC, HMBC,
      CIGAR, H2BC, and HSQC-TOCSY, along with Q-TOF HRMS2 analysis. All of the
      compounds are constituted by bayogenin as aglycone, and characterized by the
      presence of an oligosaccharide moiety, consisting of two to four sugar unities
      esterified at the C-28 carboxyl carbon. One of the isolated compounds is a
      bisdesmoside containing an additional sugar moiety at the C-3 carbon. The
      phytotoxic activity assayed against Aegilops geniculata Roth., a coexisting test
      species, has been evaluated revealing that all the compounds, at the highest
      concentrations, showed strong phytotoxicity against the leaf development.

PMID- 22959225
TI  - The enzymatic lectin of field bean (Dolichos lablab): salt assisted lectin-sugar
      interaction.
AB  - Field bean seed contains a Gal/GalNAc lectin (DLL-II) that exhibits associated
      polyphenol oxidase (PPO) activity and does not bind to its sugar specific
      affinity matrix. The molecular basis for this lack of binding is not known. The
      DLL-II gene was therefore cloned and its sequence analyzed. A conserved aromatic
      residue in the sugar binding site required for a stacking interaction with the
      apolar backbone of Gal is replaced by His in DLL-II, which explains the lack of
      binding. However, specific sugar binding is achieved by including (NH4)2SO4 in
      the buffer. Interestingly two other salts of the Hofmeister series, K2HPO4 and
      Na2SO4 also assist binding to immobilized galactose. In the presence of (NH4)2SO4
      the surface hydrophobicity of DLL-II and dissociation constant for 8-anilino 1
      naphthalene sulfonic acid were enhanced three fold. This increased surface
      hydrophobicity in the presence of salt is probably the cause for assisted sugar
      binding in legume lectins that lack aromatic stacking interactions. Accordingly,
      two other lectins which lack the conserved aromatic residue show similar salt
      assisted binding. The salt concentrations required for Gal/GalNAc binding are not
      physiologically relevant in vivo, suggesting that the role of DLL-II per se in
      the seed is primarily that of a PPO purportedly for plant defense.

PMID- 22959226
TI  - Key structural features of cis-cinnamic acid as an allelochemical.
AB  - 1-O-cis-cinnamoyl-beta-D-glucopyranose is one of the most potent allelochemicals
      isolated from Spiraea thunbergii Sieb. It is suggested that it derives its strong
      inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity.
      It was synthesized to confirm its structure and bioactivity, and also a series of
      cis-cinnamic acid analogues were prepared to elucidate the key features of cis
      cinnamic acid for lettuce root growth inhibition. The cis-cyclopropyl analogue
      showed potent inhibitory activity while the saturated and alkyne analogues proved
      to be inactive, demonstrating the importance of the cis-double bond. Moreover,
      the aromatic ring could not be replaced with a saturated ring. However, the 1,3
      dienylcyclohexene analogue showed strong activity. These results suggest that the
      geometry of the C-C double bond between the carboxyl group and the aromatic ring
      is essential for potent inhibitory activity. In addition, using several light
      sources, the photostability of the cinnamic acid derivatives and the role of the
      C-C double bond were also investigated.

PMID- 22959227
TI  - Comprehensive approaches to managing delirium in patients with advanced cancer.
AB  - Delirium is a frequently under-recognized complication in patients with advanced
      cancer. Uncontrolled delirium eventually leads to significant distress to
      patients and their families. However, delirium episodes can be reversed in half
      of these patients by eliminating precipitating factors and using appropriate
      interventions. The purpose of this narrative review is to discuss the most recent
      updates in the literature on the management of delirium in patients with advanced
      cancer. This article addresses the epidemiology, cause, pathophysiology, clinical
      characteristics, and assessment of delirium as well as various treatment options,
      including nonpharmacologic intervention and palliative sedation.

PMID- 22959228
TI  - Effects of thoracic kyphosis and forward head posture on cervical range of motion
      in older adults.
AB  - It is unclear how age-related postural changes such as thoracic spine kyphosis
      influence cervical range-of-motion (ROM) in patients with cervical spine
      dysfunction. The purpose of this study was to explore the mediating effects of
      forward head posture (FHP) on the relationship between thoracic kyphosis and
      cervical mobility in older adults with cervical spine dysfunction. Fifty-one
      older adults (30 females, mean[SD]age = 66[4.9] years) with cervical spine
      dysfunction - that is, cervical pain with or without referred pain, numbness or
      paraesthesia - participated. Pain-related disability was measured using the neck
      disability index (NDI). Thoracic kyphosis was measured using a flexicurve. FHP
      was assessed via the craniovertebral angle (CVA) measured from a digitized,
      lateral-view photograph of each subject. Cervical ROM - namely, upper and general
      cervical rotation and cervical flexion - was measured by the Cervical Range-of
      Motion (CROM) device. Greater thoracic kyphosis was significantly associated with
      lesser CVA (Spearman rho = -0.48) whereas greater CVA was significantly
      associated with greater cervical flexion (Spearman rho = 0.30) and general
      rotation ROM (rho = 0.33), but not with upper cervical rotation ROM (rho = 0.15).
      Bootstrap mediational analyses, adjusted for age, gender, weight and NDI,
      revealed significant indirect effects of thoracic kyphosis on cervical flexion
      and general rotation ROM through a FHP. Our results show that FHP mediated the
      relationship between thoracic kyphosis and cervical ROM, specifically general
      cervical rotation and flexion. These results not only support the justifiable
      attention given to addressing FHP to improve cervical impairments, but they also
      suggest that addressing thoracic kyphosis impairments may constitute an
      "upstream" approach.

PMID- 22959229
TI  - Laterality judgments are not impaired in patients with chronic whiplash
      associated disorders.
AB  - Impaired integration of the body schema with motor processes may contribute to
      painful and/or restricted movement in chronic pain. Laterality judgment tasks
      assess this integration of the body schema with motor processes. The purpose of
      this study was to assess if patients with chronic whiplash associated disorders
      (WAD) are impaired on laterality judgment tasks. Accuracy (ACC) and reaction time
      (RT) for foot and neck laterality tasks were assessed in 64 (35 female) patients
      with chronic (>6 months) WAD and 24 (14 female) asymptomatic subjects. Pain
      characteristics, post-traumatic stress symptoms, cold pain thresholds (CPT) and
      pressure pain thresholds (PPT) were collected for patients with WAD. The effect
      of WAD and body part on laterality task performance was assessed. For patients
      with WAD, the correlations between neck task performance and pain
      characteristics, post-traumatic stress symptoms and pain thresholds were
      assessed. There was no effect of group on laterality performance. Subjects showed
      better RT (p < 0.001) and ACC (p = 0.001) on the neck task in comparison to the
      foot task. There was a significant correlation between CPT and ACC (r = 0.33) and
      RT (r = -0.33) on the neck laterality task in patients with WAD. Cervical spine
      PPT were significantly correlated with accuracy (r = 0.36) and RT (r = 0.29) in
      patients with WAD. These findings suggest that patients with chronic WAD are not
      impaired on neck or foot laterality judgment tasks. Laterality training is not
      indicated in the management of chronic WAD.

PMID- 22959230
TI  - Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: a
      retrospective cohort study from Taiwan.
AB  - BACKGROUND: The development of autoimmune sequelae is one of the characteristic
      features of drug reaction with eosinophilia and systemic symptoms (DRESS) or drug
      induced hypersensitivity syndrome; however, the incidence of sequelae and
      prognosis of patients with DRESS are unknown. OBJECTIVE: We sought to investigate
      the incidence of sequelae, including less well-known sequelae, and long-term
      prognosis in patients with DRESS/drug-induced hypersensitivity syndrome. METHODS:
      A retrospective cohort study was conducted at a medical center in northern Taiwan
      using a DRESS/drug-induced hypersensitivity syndrome database. Patients who were
      followed up for at least 1 year were included in the study. RESULTS: Nine
      patients died before interview, whereas 43 patients completed a specially
      designed questionnaire. The overall cumulative incidence of long-term sequelae
      was 11.5% (6 of 52 patients). Four patients developed autoimmune diseases,
      specifically Graves disease (n = 2), type 1 diabetes mellitus (n = 1), and
      autoimmune hemolytic anemia (n = 1). Alopecia areata was also noted in 1 of the 2
      patients with Graves disease. The other 2 patients developed renal failure after
      visceral involvement and required lifetime hemodialysis. LIMITATIONS: Our study
      included a small number of patients. Further, viral studies were not performed.
      CONCLUSION: The sequelae of DRESS can be divided into 2 major types that appear
      to occur in different age groups: young patients tend to develop autoimmune
      diseases, whereas elderly patients are more vulnerable to end-organ failure.

PMID- 22959231
TI  - Why appropriate use criteria for Mohs micrographic surgery?

PMID- 22959232
TI  - AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery:
      a report of the American Academy of Dermatology, American College of Mohs
      Surgery, American Society for Dermatologic Surgery Association, and the American
      Society for Mohs Surgery.
AB  - The appropriate use criteria process synthesizes evidence-based medicine,
      clinical practice experience, and expert judgment. The American Academy of
      Dermatology in collaboration with the American College of Mohs Surgery, the
      American Society for Dermatologic Surgery Association, and the American Society
      for Mohs Surgery has developed appropriate use criteria for 270 scenarios for
      which Mohs micrographic surgery (MMS) is frequently considered based on tumor and
      patient characteristics. This document reflects the rating of appropriateness of
      MMS for each of these clinical scenarios by a ratings panel in a process based on
      the appropriateness method developed by the RAND Corp (Santa Monica,
      CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the
      rating process, consensus was reached for all 270 (100%) scenarios by the Ratings
      Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46
      (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were
      deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell
      carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34
      inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were
      deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous
      malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2
      inappropriate. These appropriate use criteria have the potential to impact health
      care delivery, reimbursement policy, and physician decision making on patient
      selection for MMS, and aim to optimize the use of MMS for scenarios in which the
      expected clinical benefit is anticipated to be the greatest. In addition,
      recognition of those scenarios rated as uncertain facilitates an understanding of
      areas that would benefit from further research. Each clinical scenario identified
      in this document is crafted for the average patient and not the exception. Thus,
      the ultimate decision regarding the appropriateness of MMS should be determined
      by the expertise and clinical experience of the physician.

PMID- 22959234
TI  - Skin involvement in cutaneous and systemic vasculitis.
AB  - Cutaneous vasculitides are a heterogeneous group of inflammatory disorders
      affecting skin blood vessels. They may be triggered by several factors, such as
      infection or drug, or may be related to underlying disease, notably connective
      tissue or malignancies. However, vasculitis occurs without any demonstrable
      triggering agents in a relevant number of patients. On the other hand, vasculitic
      skin lesions may manifest as a component of vasculitis affecting also internal
      organs; in someone of these patients, skin involvement occurs initially as the
      sole sign of disease, leading to consider cutaneous vasculitis a diagnosis of
      exclusion. In this review, we have focused on the most common variants of
      cutaneous vasculitis, including cutaneous small vessel vasculitis and urticarial
      vasculitis as well as Henoch-Schonlein purpura, a systemic form in which however
      skin involvement often predominates. We have also argued on livedoid
      vasculopathy, a cutaneous entity which, although nonfrankly vasculitic in origin,
      is frequently associated with connective tissue disease. Finally, we have
      analyzed the variety of cutaneous manifestations that may develop during the
      course of the main systemic vasculitides, such as Wegener's granulomatosis, Churg
      Strauss syndrome and polyarteritis nodosa.

PMID- 22959233
TI  - Histopathology and correlates of systemic disease in adult Henoch-Schonlein
      purpura: a retrospective study of microscopic and clinical findings in 68
      patients at Mayo Clinic.
AB  - BACKGROUND: The histopathology of Henoch-Schonlein purpura (HSP) is well defined,
      but specific markers have not been correlated with systemic involvement.
      OBJECTIVE: We sought to evaluate whether histopathologic markers were associated
      with renal or other systemic involvement in adult HSP. METHODS: We
      retrospectively reviewed clinical information and pathology slides of 68 adult
      patients with HSP seen at Mayo Clinic between 1992 and 2011. RESULTS: Of the 68
      patients, mean age was 45.8 years and 41 (60%) of the patients were male. Renal
      involvement was observed in 30 patients (44%), gastrointestinal tract in 27
      (40%), joint in 32 (47%), and any systemic signs in 52 (76%). Patients who were
      older than 40 years and had leukocytoclastic vasculitis with an absence of
      eosinophils on skin biopsy specimen had higher rates of renal involvement than
      those who did not have both of these features (75% vs 27%; P < .001). Patients
      with skin biopsy specimens showing leukocytoclastic vasculitis and an absence of
      histiocytes had higher rates of gastrointestinal tract involvement (P = .03). Age
      of 40 years or younger was associated with increased risk for gastrointestinal
      tract involvement and a nonsignificant trend for joint involvement (P = .004 and
      P = .06, respectively). LIMITATIONS: This study is retrospective, and the
      causative factors of HSP were unable to be determined in many patients.
      CONCLUSION: Patients older than 40 years with HSP who had an absence of
      eosinophils on skin biopsy specimen had a nearly 3-times increased risk of renal
      involvement compared with patients who did not have both features.

PMID- 22959235
TI  - Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with
      sporadic congenital heart disease.
AB  - BACKGROUND: Congenital heart disease is the most common birth defect in newborns
      in southern China. The germline mutations in GATA4, NKX2.5, and TFAP2B genes have
      been identified to be responsible for congenital heart disease. The frequency of
      GATA4, NKX2.5, and TFAP2B mutations in subjects with congenital heart disease in
      southern China and the correlation between their genotype and congenital heart
      disease phenotype are not known. METHODS: We screened germline mutations in the
      coding exons and the flanking intron sequences of the GATA4, NKX2.5, and TFAP2B
      genes in 224 congenital heart disease patients located in southern China by
      denaturing high-performance liquid chromatography and DNA sequencing. RESULTS:
      Fifteen heterozygous mutations in the GATA4 gene were identified in 30 congenital
      heart disease patients, including a novel heterozygous missense mutation (c.788
      C>G) of GATA4 in one patient with ventricular septal defect. A novel TFAP2B
      mutation (c.31 A>G) in a patient with endocardial cushion defect and an
      unreported novel TFAP2B variant (c.1006 G>A) in six patients suffering from
      tetralogy of Fallot (one patient), persistent truncus arteriosus (two patients)
      and patent ductus arteriosus (three patients) was found. There were no reported
      NKX2.5 mutations except for several single nucleotide polymorphisms in the
      patients. CONCLUSION: These results suggest that genomic GATA4 and TFAP2B
      missense mutations may be associated with nonfamilial congenital heart disease
      with diverse clinical phenotypes in patients with congenital heart disease from
      southern China. They also revealed that the variation of the NKX2.5 gene may not
      be a risk factor for sporadic patients with congenital heart disease in this
      population.

PMID- 22959236
TI  - Transforming growth factor-beta and abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) are common problems in aged people which can be
      associated with severe complications including aortic rupture and death.
      Transforming growth factor-beta (TGFbeta) has been implicated as causative in the
      development of thoracic aortic aneurysms (TAAs). In contrast, current evidence
      suggests TGFbeta inhibits AAA development. Polymorphisms in the TGFbeta signaling
      components are associated with AAA in some human population studies. In
      experimental animals TGFbeta protects against AAA formation, progression and
      rupture. In animal models of AAA TGFbeta decreases aortic inflammatory cell
      infiltration, extracellular matrix degradation, and vascular smooth muscle cell
      apoptosis, all factors implicated in AAA pathogenesis. The TGFbeta signaling
      pathway may provide a therapeutic target for AAA although better clarity is
      needed regarding the distinct roles of TGFbeta in TAA and AAA.

PMID- 22959237
TI  - Conversion from bipolar disorder not otherwise specified (BP-NOS) to bipolar I or
      II in youth with family history as a predictor of conversion.
AB  - BACKGROUND: Bipolar disorder-not otherwise specified (BD-NOS) is an imprecise,
      heterogeneous diagnosis that is unstable in youth. This study reports rates of
      conversion from BD-NOS to BD-I or II in children aged 8-12, and investigates the
      impact of family history of bipolar disorder and depression on conversion.
      METHODS: As part of the Multi-Family Psychoeducational Psychotherapy (MF-PEP)
      study, 27 children (6-12 years of age) diagnosed with BD-NOS at baseline were
      reassessed every 6 months over an 18-month period. Family history of bipolar
      disorder and depression was assessed at baseline. RESULTS: One-third of the
      sample converted from BD-NOS to BD-I or II over 18-months. Having a first-degree
      relative with symptoms of bipolar disorder and having a loaded pedigree for
      diagnosis of depression each were associated with conversion from BD-NOS to BD-I
      or II (odds ratio range: 1.09-3.14; relative risk range: 1.06-2.34). LIMITATIONS:
      This study had very low power (range: 10-45) given the small sample size,
      precluding statistical significance of non-parametric Fisher's Exact test
      findings. CONCLUSIONS: This study replicates the previous finding of a high rate
      of conversion from BD-NOS to BD-I or II among youth, and suggests conversion is
      related to symptoms of bipolar disorder or depression diagnoses in the family
      history. Additional research is warranted in a larger sample with a longer follow
      up period.

PMID- 22959238
TI  - Classic manifestations of Duchenne dystrophy in a young female patient: a case
      report.
AB  - Duchenne and Becker muscular dystrophies (DMD/DMB) are neuromuscular diseases
      linked to chromosome X and affect mainly male individuals. Duchenne muscular
      dystrophy is the most severe form of the disease, leading to a decreased patient
      survival compared with individuals with Becker type and female carriers of the
      mutated gene. In this paper we present the case of a female adolescent whose
      clinical picture and disease course closely resembled male individuals.

PMID- 22959239
TI  - WAAR (World Alliance against Antibiotic Resistance): safeguarding antibiotics.

PMID- 22959240
TI  - BDNF expression with functional improvement in transected spinal cord treated
      with neural stem cells in adult rats.
AB  - Neural stem cells (NSC) could promote the repair after spinal cord transection
      (SCT), the underlying mechanism, however, still keeps to be defined. This study
      reported that NSC grafts significantly improved sensory and locomotor functions
      in adult rats with SCT in acute stage after injury. NSC could survive;
      differentiate towards neurons or glia lineage in vitro and vivo. Biotin dextran
      amine (BDA) tracing showed that little CST regeneration in the injury site, while
      SEP was recorded in NSC engrafted rats. Immunohistochemistry and Real time PCR
      confirmed that engrafted NSC expressed BDNF and increased the level of BDNF mRNA
      in injured site following transplantation. The present data therefore suggested
      that the functional recovery following SCT with NSC transplantation was
      correlated with the expression of BDNF, indicating the usage of BDNF with NSC
      transplantation in the treatment of SCI following injury.

PMID- 22959241
TI  - Unsuspected pulmonary embolism in lung cancer patients: comparison of clinical
      characteristics and outcome with suspected pulmonary embolism.
AB  - PURPOSE: Compare the clinical characteristics, rate of recurrent venous
      thromboembolism (VTE) and outcome of suspected and unsuspected pulmonary embolism
      (PE) detected on computed tomography in patients with lung cancer. METHODS: In
      this IRB-approved retrospective study, 77 patients [38 men, 39 women; mean age 64
      (range, 35-90)] with lung cancer who developed PE between January 2004 and
      December 2009 were identified using research patient data registry and medical
      records. Patients with suspected (45/77, 58%) and unsuspected (32/77, 42%) PE
      were compared for the characteristics, treatment of PE, and rate of recurrent VTE
      using Fisher's exact test. The survival was compared using log-rank test, and Cox
      proportional hazards regression models were applied for univariate and
      multivariable analyses. RESULTS: Most cases of PE were found in patients
      undergoing chemotherapy (79%) and with metastatic disease (70%). Suspected PE
      more commonly involved main/lobar pulmonary arteries (33/45, 73% vs. 9/32, 28%),
      while unsuspected PE more frequently involved of segmental/subsegmental arteries
      (p=0.0001). All 11 cases of squamous cell carcinoma had suspected PE. Suspected
      and unsuspected PE did not differ in terms of age, gender, presence of metastatic
      disease at the time of PE or treatment for PE. 44/45 (98%) patients with
      suspected PE and 30/32 (94%) patients with unsuspected PE were treated for PE,
      mostly with anticoagulation (68/74, 92%). Recurrent VTE was seen in 20% (9/45) of
      suspected PE and 19% (6/32) of unsuspected PE (p=1.00). Median survival after PE
      was 5.6 months in suspected group and 6.2 month in unsuspected group, without
      significant difference by univariate or multivariate analyses. CONCLUSION:
      Although unsuspected PE more frequently involved peripheral pulmonary arteries,
      the treatments of PE, bleeding complications, rates of recurrent VTE, and
      survival after PE were similar for clinically suspected and unsuspected PE.

PMID- 22959242
TI  - Metformin does not alter the risk of lung cancer: a case-control analysis.
AB  - BACKGROUND: Metformin use has been linked to a decreased cancer risk. We explored
      the association between use of metformin or other antidiabetic drugs and the risk
      of lung cancer. METHODS: We assessed the association between metformin, and other
      antidiabetic drugs and lung cancer using a case-control analysis in the UK-based
      General Practice Research Database (GPRD). Cases were people with an incident
      diagnosis of lung cancer. Up to 6 controls per case were matched on age, sex,
      calendar time, general practice, and number of years of active history in the
      GPRD. The contribution of potential confounders including tuberculosis, chronic
      obstructive pulmonary disease (COPD), diabetes mellitus, and co-morbid conditions
      to diabetes was evaluated in univariate models, and final results were adjusted
      for BMI and smoking. RESULTS: Long-term use (>=40 prescriptions) of metformin was
      not associated with an altered risk of lung cancer (adj. OR 1.21, 95% CI 0.97
      1.50. Long-term use of sulfonylureas was linked to a marginally decreased risk of
      lung cancer (adj. OR 0.74, 95% CI 0.60-0.90. This risk decrease was observed in
      men (adj. OR 0.64, 95% CI 0.50-0.83) but not in women (adj. OR 0.97, 95% CI 0.69
      1.37) and this risk decrease was not statistically significant in an analysis
      restricted to diabetic patients only (adj. OR. 0.82, 95% CI 0.65-1.02). Long-term
      use of insulin was associated with a slightly increased risk of lung cancer (adj.
      OR 1.33, 95% CI 1.04-1.71); however, no consistent trend across duration strata
      was observed. CONCLUSION: Metformin did not decrease the risk of lung cancer.

PMID- 22959243
TI  - HCV NS5A replication complex inhibitors. Part 2: investigation of stilbene
      prolinamides.
AB  - In a previous disclosure,(1) we reported the dimerization of an
      iminothiazolidinone to form 1, a contributor to the observed inhibition of HCV
      genotype 1b replicon activity. The dimer was isolated via bioassay-guided
      fractionation experiments and shown to be a potent inhibitor of genotype 1b HCV
      replication for which resistance mapped to the NS5A protein. The elements
      responsible for governing HCV inhibitory activity were successfully captured in
      the structurally simplified stilbene prolinamide 2. We describe herein the early
      SAR and profiling associated with stilbene prolinamides that culminated in the
      identification of analogs with PK properties sufficient to warrant continued
      commitment to this chemotype. These studies represent the key initial steps
      toward the discovery of daclatasvir (BMS-790052), a compound that has
      demonstrated clinical proof-of-concept for inhibiting the NS5A replication
      complex in the treatment of HCV infection.

PMID- 22959244
TI  - Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly
      selective 5-HT(4) receptor agonist that has achieved proof-of-concept in patients
      with chronic idiopathic constipation.
AB  - Utilization of Theravance's multivalent approach to drug discovery towards 5
      HT(4) receptor agonists with a focus on identification of neutral (non-charged at
      physiological pH) secondary binding groups is described. Optimization of a
      quinolone-tropane primary binding group with a chiral 2-propanol linker to a
      range of neutral secondary binding group motifs, for binding affinity and
      functional potency at the 5-HT(4) receptor, selectivity over the 5-HT(3)
      receptor, oral pharmacokinetics, and in vivo efficacy in models of GI motility,
      afforded velusetrag (TD-5108). Velusetrag has achieved proof-of-concept in
      patients with chronic idiopathic constipation.

PMID- 22959245
TI  - A sigma(1) receptor pharmacophore derived from a series of N-substituted 4
      azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols (AHDs).
AB  - A library of N-substituted 4
      azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols (AHDs) was
      synthesized and subjected to competition binding assays at sigma(1) and sigma(2)
      receptors, as well as off-target screening of representative members at 44 other
      common central nervous system (CNS) receptors, transporters, and ion channels.
      Excluding 3 low affinity analogs, 31 ligands demonstrated nanomolar K(i) values
      for either sigma receptor subtype. Several selective sigma(1) and sigma(2)
      ligands were discovered, with selectivities of up to 29.6 times for sigma(1) and
      52.4 times for sigma(2), as well as several high affinity, subtype non-selective
      ligands. The diversity of structures and sigma(1) affinities of the ligands
      allowed the generation of a sigma(1) receptor pharmacophore that will enable the
      rational design of increasingly selective and potent sigma(1) ligands for probing
      sigma(1) receptor function.

PMID- 22959246
TI  - Camptothecins in tumor homing via an RGD sequence mimetic.
AB  - A RGD peptide mimetic was conjugated to four camptothecins, with the purpose to
      improve their therapeutic index. The conjugate derivatives were evaluated against
      two tumor cell lines, one overexpressing integrins (human ovarian carcinoma,
      A2780) and a second one with a low integrin expression (human prostate cancer,
      PC3). The in vitro screening was completed with the adhesion behavior to
      vitronectin. Compound 8 (ST7456CL1) was selected for the in vivo investigation
      after stability tests over 24h, in PBS solution and in rat plasma, and compared
      to irinotecan. The former showed a prolonged half-life.

PMID- 22959247
TI  - Isomannide derivatives as new class of inhibitors for human kallikrein 7.
AB  - Human kallikrein 7 (KLK7) is a potential target for the treatment of skin
      inflammation and cancer. Despite its potential, few KLK7-specific small-molecule
      inhibitors have been reported in the literature. As an extension of our program
      to design serine protease inhibitors, here we describe the in vitro assays and
      the investigation of the binding mechanism by molecular dynamics simulation of a
      novel class of pseudo-peptide inhibitors derived from isomannide. Of the
      inhibitors tested, two inhibited KLK7 with K(i) values in the low micromolar
      range (9g=1.8MUM; 9j=3.0MUM). Eadie-Hofstee and Dixon plots were used to evaluate
      the competitive mechanism of inhibition for the molecules. Calculated binding
      free energies using molecular MM/PB(GB)SA approach are in good agreement with
      experimental results, suggesting that the inhibitors share the same binding mode,
      which is stabilized by hydrophobic interactions and by a conserved network of
      hydrogen bonds. The promising results obtained in this study make these compounds
      valid leads for further optimization studies aiming to improve the potency of
      this new class of kallikrein inhibitors.

PMID- 22959248
TI  - Synthesis and biological evaluation of crown ether fused quinazoline analogues as
      potent EGFR inhibitors.
AB  - Crown ether fused anilinoquinazoline analogues were synthesized as novel
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
      Representative compounds showed potent and selective EGFR inhibitory activities
      in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine
      phosphorylation assay. The synthesis and preliminary biological, physical, and
      pharmacokinetic evaluation of these fused quinazoline compounds is reported.

PMID- 22959249
TI  - JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers
      related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS
      liabilities.
AB  - Analogs of SLV-319 (Ibipinibant), a CB1 receptor inverse agonist, were
      synthesized with functionality intended to limit brain exposure while maintaining
      the receptor affinity and selectivity of the parent compound. Structure activity
      relationships of this series, and pharmacology of two lead compounds, 16 (JD
      5006) and 23 (JD-5037) showing little brain presence as indicated by tissue
      distribution and receptor occupancy studies, are described. Effects with one of
      these compounds on plasma triglyceride levels, liver weight and enzymes, glucose
      tolerance and insulin sensitivity support the approach that blockade of
      peripheral CB(1) receptors is sufficient to produce many of the beneficial
      metabolic effects of globally active CB(1) blockers. Thus, PR CB(1) inverse
      agonists may indeed represent a safer alternative to highly brain-penetrant
      agents for the treatment of metabolic disorders, including diabetes, liver
      diseases, dyslipidemias, and obesity.

PMID- 22959250
TI  - Reoperation for failed rotator cuff repair: Analysis of fifty cases.
AB  - Fifty patients who underwent reoperation for failure of previous repair of
      rotator cuff rupture were evaluated 24 to 84 months after final repair (mean 30
      months). Forty-eight of these patients had undergone all previous attempts at
      repair elsewhere. Most patients had had one or two earlier attempts, but four
      patients had had three, and three patients had had four. Forty-six (92%) patients
      reported pain improvement, and four were unchanged. Twenty-six patients showed an
      average increase in elevation of 50 degrees  (range 10 degrees  to 130 degrees ).
      Twenty-two retained their preoperative motion, and two lost motion (mean 45
      degrees ) but still had more than 90 degrees . Overall mean elevation increased
      from 92 degrees  to 137 degrees . Compared with 17 patients before surgery, only
      six had less than 90 degrees  motion after surgery-and all six had deltoid
      abnormalities. The size of the rupture, the number of previous operations, and
      dysfunction of the biceps did not affect the result. The following factors were
      associated with success: adequate decompression, closure of all defects with
      tendon-to-bone junctures (by direct repair, interpositional grafting, or local
      tendon transfers), avoiding use of weights or resistive exercises during the
      early (first 3 months) postoperative rehabilitation period, and an intact,
      functioning deltoid.

PMID- 22959251
TI  - Open reduction and internal fixation of two- and three-part displaced surgical
      neck fractures of the proximal humerus.
AB  - Twenty-two patients aged 20 to 82 years (average 56 years) were followed for 1.1
      to 8.9 years (average 3.3 years) after open reduction and internal fixation of
      two- and three-part displaced surgical neck fractures of the proximal humerus.
      There were 14 two-part displaced surgical neck fractures, seven three-part
      displaced greater tuberosity and surgical neck fractures, and one three-part
      displaced lesser tuberosity and surgical neck fracture. Fixation was achieved
      with heavy nonabsorbable sutures or wire that incorporated the rotator cuff
      tendons, tuberosities, and shaft. In cases with significant surgical neck
      comminution, humeral Enders nails were incorporated in a tension-band construct
      to provide longitudinal stability. Eighteen (82%) of the 22 patients had good or
      excellent results. Three (14%) of the 22 had satisfactory results, and one (5%)
      had an unsatisfactory result. The use of a technique of limited internal fixation
      for these displaced fractures without the use of plates and screws achieved
      fracture stability and a high percentage of acceptable results.

PMID- 22959252
TI  - Humeroscapular positions in a shoulder range-of-motion-examination.
AB  - Positions of the arm are traditionally described in relation to the thorax. Yet
      shoulder pathology most often lies in and about the glenohumeral joint, which
      then becomes the focus of treatment. Little is known about the relative motion
      between the humerus and the scapula primarily because there is no clinically
      accepted method for assessing and describing these positions. This paper proposes
      a clinical method for describing and measuring humeroscapular positions based on
      an anatomic definition of the plane of the scapula. Humeroscapular positions
      achieved by 75 normal subiects during a conventional (humerothoracic) shoulder
      range-of-motion examination are presented. Identification of the plane of the
      scapula is based on four palpable anatomic landmarks: (7) the inferior pole of
      the scapula, (2) the medial border of the scapula at the level of the scapular
      spine, (3) the posterolateral corner of the acromion, and (4) the tip of the
      coracoid. The plane of the scapula is defined by the line connecting the first
      two of these points and a point midway between the last two. Humeroscapular
      positions are specified by the plane of elevation and the angle of elevation in
      relation to this mobile scapular plane. Measurement of these positions was done
      with a goniometer facilitated by a "scapula-locating device" designed for this
      study. Maximal humerothoracic elevation of the arm was achieved with the humerus
      lust behind the scapular plane at 90 degrees  of humeroscapular elevation. Cross
      body adduction positioned the humerus in a plane 51 degrees  anterior to the
      plane of the scapula, with most of the cross-body motion occurring between the
      scapula and thorax. External rotation at 90 degrees  of elevation in the coronal
      plane of the body (the apprehension position) positioned the humerus in a plane
      17 degrees  posterior to the scapular plane. Humerothoracic extension and
      reaching up the back took place at very low angles of humeroscapular elevation.

PMID- 22959253
TI  - Fluoroscopically positioned radiographs of total shoulder arthroplasty.
AB  - Between January 1990 and January 1991, 87 patients (100 shoulder arthroplasties)
      were radiographically examined with both standard and fluoroscopically positioned
      views. The sets of radiographs were compared and assessed for acceptability (the
      ability to interpret the interfaces), presence or absence of radiolucent zones,
      and differences between size and location of radiolucent zones. Fifty-six of the
      standard radiographs were unacceptable because of obliquity of the x-ray beam
      protection; only three localized views were unacceptable (p < 0.0001). Nineteen
      of the unacceptable standard views had radiolucent zones detected on the
      comparable fluoroscopic views. Forty-four radiographic sets were acceptable for
      evaluation. Of these, 27 sets had no differences; standard views showed the
      interface changes better in one, and localized views were better in 76 (p <
      0.001). Thus in 68 of 100 total shoulder arthroplasties evaluated, clinical
      information that was not seen on standard radiographs was identified on
      fluoroscopic views. We conclude that fluoroscopic positioning is superior to
      standard radiographs in detecting implant-bone interface changes.

PMID- 22959254
TI  - Glenohumeral translation after total shoulder arthroplasty.
AB  - To define the amount and direction of anteroposterior translation of the
      glenohumeral joint after total shoulder arthroplasty, 13 patients who had
      previously undergone nonconstrained total shoulder arthroplasty were studied
      roentgenographically. Patients were placed on the x-ray table in a supine
      position, and axillary roentgenograms of the shoulder were made with the arm at
      90 degrees  abduction and in four positions within the horizontal plane of
      motion: - 30 degrees  (horizontal extension), 0 degrees  (neutral), 30 degrees ,
      and 60 degrees  (horizontal flexion). For all positions the shoulder was in
      neutral rotation. The center of the prosthetic humeral head was identified, and
      the distance between it and a perpendicular line bisecting the glenoid component
      was measured. At follow-up the patients had statistically significant
      improvements in pain, motion, and function. No patients had any clinical evidence
      of instability. The mean total translation was 4 mm posteriorly (range 0 to 12
      mm). Most translation occurred between - 30 degrees  and 30 degrees .
      Anteroposterior translation appears to occur in a posterior direction. For this
      to occur the prosthetic humeral head slides onto the polyethylene rim of the
      glenoid component, subjecting it to eccentric loading and the possibilities of
      wear, polyethylene debris formation, induction of osteolysis, and subsequent
      component loosening.

PMID- 22959255
TI  - Acromion nonunion after anterior acromioplasty: A case report.

PMID- 22959256
TI  - The use of magnetic resonance imaging about the shoulder.

PMID- 22959257
TI  - A portable auditory P300 brain-computer interface with directional cues.
AB  - OBJECTIVES: The main objective of the current study was to implement and evaluate
      a P300 based brain-computer interface (BCI) speller that uses directional cues of
      auditory stimuli, which are presented over headphones. The interstimulus interval
      (ISI) was successively reduced to determine the optimal combination of speed and
      accuracy. The study further aimed at quantifying the differences in subjective
      workload between the auditory and the visual P300 spelling application. The
      influence of workload, mood and motivation on BCI performance and P300 amplitude
      was investigated. METHODS: Twenty healthy participants performed auditory and
      visual spelling tasks in an EEG experiment with online feedback. RESULTS: Sixteen
      of twenty participants performed at or above a level necessary for satisfactory
      communication (>=70% spelling accuracy) with the auditory BCI. Average bit rates
      of up to 2.76 bits/min (best subject 7.43 bits/min) were achieved. A
      significantly higher workload was reported for the auditory speller compared to
      the visual paradigm. Motivation significantly influenced P300 amplitude at Pz in
      the auditory condition. CONCLUSIONS: The results of the online study suggest that
      the proposed paradigm offers a means of communication for most healthy users.
      SIGNIFICANCE: The described auditory BCI can serve as a communication channel for
      completely paralyzed patients.

PMID- 22959258
TI  - Avoiding never events: improving nasogastric intubation practice and standards.
AB  - AIM: To identify and rectify weaknesses in nasogastric (NG) intubation practice
      in the North Bristol NHS Trust that resulted in the occurrence of a National
      patient Safety Agency defined "never event". MATERIAL AND METHODS: Root-cause
      analysis identified that a change in culture was required. Recommendations
      divided into four categories: documentation, intubation, interpretation training,
      and radiology. A 6 month prospective audit covering all aspects of NG intubation
      practice preceded implementation of the recommendations. All patients whose tubes
      were mis-sited formed the cohort of the study. A re-audit was undertaken 12
      months after the implementation of the recommended changes. RESULTS: Re-audit
      suggested significant improvements had occurred in all categories, particularly
      junior doctor check image interpretation errors, which in the study group were
      reduced from seven to one, and documentation, which has so far improved by 22%.
      Protocols and guidelines associated with NG tube check imaging have now been
      developed for radiologists and radiographers with check imaging and image
      interpretation being made a priority and respiratory tract intubation treated as
      an emergency. CONCLUSION: The service is still not perfect, but there is a focal
      awareness of patient safety associated with intubation practice, and image
      interpretation by junior doctors significantly improved with the introduction of
      the e-learning package. However, it is considered that the responsibility for
      developing safe practice with respect to NG tube check image interpretation
      ultimately lies with the department of radiology, which should take the lead on
      reducing the risk of never events being caused by the misinterpretation of these
      images.

PMID- 22959259
TI  - The role of MRI and CT of the brain in first episodes of psychosis.
AB  - AIM: To investigate whether imaging is associated with early detection of the
      organic causes of the first episode of psychosis (FEP). MATERIALS AND METHODS:
      Individuals with FEP but no neurological signs referred to a tertiary centre for
      cerebral magnetic resonance imaging (MRI) or computed tomography (CT) were
      reviewed retrospectively. Two groups were evaluated with either CT or MRI; the
      two groups were independent and no individual underwent both CT and MRI. RESULTS:
      One hundred and twelve consecutive cerebral MRI and 204 consecutive CT
      examinations were identified. Three (2.7%) individuals had brain lesions [brain
      tumour and human immunodeficiency virus (HIV) encephalopathy] potentially
      accountable for the psychosis at MRI. Seventy patients (62.5%) had incidental
      brain lesions, such as cerebral atrophy, small vessel ischaemic changes,
      unruptured Circle of Willis aneurysm, cavernoma, and arachnoid cysts at MRI.
      Three patients (1.5%) had focal brain lesions (primary or secondary tumours)
      potentially accountable for the psychosis at CT. One hundred and thirty-three
      patients (65.2%) had incidental brain lesions unrelated to the psychosis on CT
      scan. There was no significant difference between MRI and CT imaging in detecting
      organic disease potentially responsible for FEP (p < 0.001). CONCLUSION: Routine
      MRI or CT imaging of the brain is unlikely to reveal disease leading to a
      significant change in management. MRI was comparable with CT in terms of
      diagnosis of both pathological and incidental cerebral lesions. Therefore,
      routine brain structural imaging of FEP in patients without focal neurology may
      not be routinely required and if imaging is requested then CT may function
      equally as well as MRI as the first-line investigation.

PMID- 22959260
TI  - 2012 Gerard W. Ostheimer Lecture--What's new in obstetric anesthesia?
AB  - The aim of the 2012 "What's new in obstetric anesthesia?" review is to highlight
      important scientific and medical advances in the fields of obstetric
      anesthesiology, obstetrics and perinatology from literature published in 2011.
      This review will consider advances in the prevention and treatment of important
      obstetric and obstetric anesthesia-related morbidities, research relevant to the
      course of labor and electronic fetal monitoring, and advances in neuraxial
      analgesia and anesthesia for obstetric patients.

PMID- 22959261
TI  - Acute pancreatitis in pregnancy: review of three cases and anaesthetic
      management.
AB  - Acute pancreatitis is rare in pregnancy, with an estimated incidence of 1 in 1000
      3000 pregnancies. Gallstones are the commonest cause. Mortality and morbidity
      associated with pancreatitis have declined as diagnosis and management options
      improve. Presentation usually occurs in the third trimester or early postpartum
      period with severe epigastric pain, nausea, vomiting, anorexia and fever. Blood
      investigations show an elevated white cell count and increased liver enzyme
      concentrations. Ultrasound is safe but has lower sensitivity than computerised
      tomography for detecting gallstones. Management during pregnancy has
      traditionally been conservative, followed by cholecystectomy after delivery.
      Recurrence of pancreatitis during pregnancy may necessitate more urgent surgery.
      The second trimester is considered the safest for surgery, with early involvement
      of intensive care as the condition can deteriorate rapidly. We present three
      cases managed in our unit over a six-month period that illustrate the spectrum of
      disease and the successful use of a multidisciplinary team approach.

PMID- 22959262
TI  - Can the passive leg raise test predict spinal hypotension during cesarean
      delivery? An observational pilot study.
AB  - BACKGROUND: It was hypothesized that patients who are preload dependent, as
      demonstrated by a >12% increase in cardiac output in response to a passive leg
      raise test, would be more likely to exhibit hypotension during spinal anesthesia
      for cesarean delivery. METHODS: Cardiac output response to the passive leg raise
      test was measured in 40 women before spinal anesthesia with a noninvasive,
      continuous cardiac output monitor (NICOM(r)). Patients were divided into two
      groups based on their performance on the passive leg raise test; those who
      increased cardiac output >12% following passive leg raise test were considered
      fluid responsive. NICOM(r) hemodynamic values were collected from the onset of
      spinal anesthesia until 10min after delivery of the fetus. The incidence of
      hypotension, defined as mean arterial blood pressure <70% of the patient's
      baseline value was compared between the two groups. Vasopressor use, umbilical
      cord blood gases and Apgar scores were also compared between the groups. RESULTS:
      Nine patients were fluid responsive and 31 were fluid non-responsive. The groups
      had similar demographics and baseline hemodynamic parameters. No significant
      differences were seen between the groups in the incidence of spinal hypotension,
      vasopressor use, or neonatal outcome. At the time of delivery, fluid responsive
      patients had larger cardiac outputs compared to fluid non-responsive patients.
      CONCLUSIONS: In this pilot study, non-invasive assessment of the hemodynamic
      response to a volume load was not predictive of hypotension or vasopressor use
      during cesarean delivery under spinal anesthesia. Fluid responsiveness was
      related to hemodynamic responses at delivery.

PMID- 22959263
TI  - Physicochemical characterization and sorption behavior of Mg-Ca-Al (NO3)
      hydrotalcite-like compounds toward removal of fluoride from protein solutions.
AB  - The present study explores the potential of Mg-Ca-Al (NO(3)) hydrotalcite-like
      compounds (MgCaAlNO(3)-HTlcs) for the removal of fluoride from protein solutions.
      In this study, the Mg(3-x)Ca(x)AlNO(3)-HTlcs (x=0-3, x is the mol.% of Ca) were
      synthesized and characterized by SEM, XRD, FTIR, BET, ICP-AES and pHzpc analysis.
      The sorption experiments were conducted in protein systems of bovine serum
      albumin (BSA) and lysozyme (LSZ). The batch experiment results showed that the
      NO(3)-HTlc with Mg/Ca/Al molar ratio of 2.5/0.5/1 had remarkable fluoride
      sorption ability with maximum sorption capacities of 82.35 mg/g and 72.69 mg/g at
      pH 5.0 and 40 degrees C in BSA and LSZ system, respectively. Moreover, the loss
      of BSA of 0.71% was low and there was no loss of LSZ. It was evident that the
      Mg(2.5)Ca(0.5)AlNO(3)-HTlc could selectively adsorb fluoride from protein
      solutions. The equilibrium sorption data fitted well to the Langmuir model and
      the kinetic data conformed to the pseudo-second-order model. Thermodynamic
      parameters (DeltaG degrees , DeltaH degrees  and DeltaS degrees ) were evaluated
      and revealed that the sorption process was spontaneous and endothermic in nature.
      Furthermore, the results from Antarctic krill processing wastewater study
      confirmed the feasibility and practicality of the Mg(2.5)Ca(0.5)AlNO(3)-HTlc for
      fluoride removal in fluoride bearing protein system.

PMID- 22959264
TI  - A new method for analysis of the toxicity of organophosphorus pesticide,
      dimethoate on rotifer based on response surface methodology.
AB  - This study analyzed the toxicity of organophosphorus pesticide, dimethoate on
      freshwater rotifer Brachionus calyciflorus, using swimming angular and linear
      speed alteration as the sub-lethal endpoints. Response surface methodology (RSM)
      was applied in experimental design and data analysis to consider two related
      factors: toxic concentration, exposure time and their interaction. In general,
      inhibition effect of the pesticide on rotifer swimming was observed clearly at
      any given toxicant concentration. The highest inhibition rates in angular and
      linear speed were obtained in the shortest exposure time (11.36 min) and the
      highest dimethoate concentration (1.85 mg L(-1)). The RSM used for the analysis
      of treatment combinations showed that a cubic polynomial regression model was in
      good agreement with experimental results, with R(2)=0.992 and 0.9997, for
      swimming angular speed inhibition rate and linear speed inhibition rate (p<0.01,
      F-test, respectively). 3D reference surface plots and contour plots showed that
      the toxic effect was influenced not only by dimethoate concentration, but also by
      the exposure time. A time-step effect was observed clearly. Thus, the pesticide
      dimethoate had toxic stress on the swimming behavior of rotifers.

PMID- 22959265
TI  - Evaluation of the antifouling and photocatalytic properties of poly(vinylidene
      fluoride) plasma-grafted poly(acrylic acid) membrane with self-assembled TiO2.
AB  - Immobilization of TiO(2) is a promising approach that produces antifouling and
      photocatalytic membranes that could help advance wastewater treatment and re-use
      processes. In this study, poly(acrylic acid) (PAA) was plasma-grafted on
      commercial poly(vinylidene fluoride) (PVDF) to introduce functional groups on the
      membrane surface that can support the nanoparticles. It was found that plasma
      treatment at 100 W for 120 s followed by liquid grafting with 70% aqueous AA at
      60 degrees C for 2h maximized the number of TiO(2) binding sites. Membrane
      hydrophilicity was tremendously enhanced by the self-assembly of TiO(2),
      following a direct proportionality to TiO(2) loading. The membrane with 0.5%
      TiO(2) loading maintained the highest pure water flux and the best protein
      antifouling property. UV irradiation triggered the photodegradation of strongly
      bound foulants, but at least 1.5% TiO(2) and 30 min cumulative irradiation were
      necessary to completely recover the membrane's original performance. The TiO(2)
      modified membranes removed 30-42% of 50mg/l aqueous Reactive Black 5 (RB5) dye.
      The fabricated membranes demonstrate huge potential for use in membrane reactors
      with high hydrophilicity, fouling mitigation, and photocatalytic capability.

PMID- 22959266
TI  - Enhanced remediation of chlorpyrifos from soil using ryegrass (Lollium
      multiflorum) and chlorpyrifos-degrading bacterium Bacillus pumilus C2A1.
AB  - The combined use of plants and associated microorganisms has great potential for
      remediating soil contaminated with organic compounds such as pesticides. The
      objective of this study was to determine whether the bacterial inoculation
      influences plant growth promotion and chlorpyrifos (CP) degradation and
      accumulation in different parts of the plant. Ryegrass was grown in soil spiked
      with CP and inoculated with a pesticide degrading bacterial strain Bacillus
      pumilus C2A1. Inoculation generally had a beneficial effect on CP degradation and
      plant biomass production, highest CP degradation (97%) was observed after 45 days
      of inoculation. Furthermore, inoculated strain efficiently colonized in the
      rhizosphere of inoculated plant and enhanced CP and its primary metabolite 3,5,6
      trichloro-2-pyridinol (TCP) degradation. There was significantly less CP
      accumulation in roots and shoots of inoculated plants as compared to uninoculated
      plants. The results show the effectiveness of inoculated exogenous bacteria to
      boost the remediation of CP contaminated sites and decrease levels of toxic
      pesticide residues in crop plants.

PMID- 22959269
TI  - Architecture of the nuclease module of the yeast Ccr4-not complex: the Not1-Caf1
      Ccr4 interaction.
AB  - Shortening eukaryotic poly(A) tails represses mRNA translation and induces mRNA
      turnover. The major cytoplasmic deadenylase, the Ccr4-Not complex, is a conserved
      multisubunit assembly. Ccr4-Not is organized around Not1, a large scaffold
      protein that recruits two 3'-5' exoribonucleases, Caf1 and Ccr4. We report
      structural studies showing that the N-terminal arm of yeast Not1 has a HEAT
      repeat structure with domains related to the MIF4G fold. A MIF4G domain
      positioned centrally within the Not1 protein recognizes Caf1, which in turn binds
      the LRR domain of Ccr4 and tethers the Ccr4 nuclease domain. The interactions
      that form the nuclease core of the Ccr4-Not complex are evolutionarily conserved.
      Their specific disruption affects cell growth and mRNA deadenylation and decay in
      vivo in yeast. Thus, the N-terminal arm of Not1 forms an extended platform
      reminiscent of scaffolding proteins like eIF4G and CBP80, and places the two
      nucleases in a pivotal position within the Ccr4-Not complex.

PMID- 22959267
TI  - Transcription of two long noncoding RNAs mediates mating-type control of
      gametogenesis in budding yeast.
AB  - The cell-fate decision leading to gametogenesis is essential for sexual
      reproduction. In S. cerevisiae, only diploid MATa/alpha but not haploid MATa or
      MATalpha cells undergo gametogenesis, known as sporulation. We find that
      transcription of two long noncoding RNAs (lncRNAs) mediates mating-type control
      of sporulation. In MATa or MATalpha haploids, expression of IME1, the central
      inducer of gametogenesis, is inhibited in cis by transcription of the lncRNA
      IRT1, located in the IME1 promoter. IRT1 transcription recruits the Set2 histone
      methyltransferase and the Set3 histone deacetylase complex to establish
      repressive chromatin at the IME1 promoter. Inhibiting expression of IRT1 and an
      antisense transcript that antagonizes the expression of the meiotic regulator
      IME4 allows cells expressing the haploid mating type to sporulate with kinetics
      that are indistinguishable from that of MATa/alpha diploids. Conversely,
      expression of the two lncRNAs abolishes sporulation in MATa/alpha diploids. Thus,
      transcription of two lncRNAs governs mating-type control of gametogenesis in
      yeast.

PMID- 22959268
TI  - Set3 HDAC mediates effects of overlapping noncoding transcription on gene
      induction kinetics.
AB  - The Set3 histone deacetylase complex (Set3C) binds histone H3 dimethylated at
      lysine 4 (H3K4me2) to mediate deacetylation of histones in 5'-transcribed
      regions. To discern how Set3C affects gene expression, genome-wide transcription
      was analyzed in yeast undergoing a series of carbon source shifts. Deleting SET3
      primarily caused changes during transition periods, as genes were induced or
      repressed. Surprisingly, a majority of Set3-affected genes are overlapped by
      noncoding RNA (ncRNA) transcription. Many Set3-repressed genes have H3K4me2
      instead of me3 over promoter regions, due to either reduced H3K4me3 or ncRNA
      transcription from distal or antisense promoters. Set3C also represses internal
      cryptic promoters, but in different regions of genes than the Set2/Rpd3S pathway.
      Finally, Set3C stimulates some genes by repressing an overlapping antagonistic
      antisense transcript. These results show that overlapping noncoding transcription
      can fine-tune gene expression, not via the ncRNA but by depositing H3K4me2 to
      recruit the Set3C deacetylase.

PMID- 22959270
TI  - Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and
      expansions in dividing and nondividing yeast cells.
AB  - Triplex structure-forming GAA/TTC repeats pose a dual threat to the eukaryotic
      genome integrity. Their potential to expand can lead to gene inactivation, the
      cause of Friedreich's ataxia disease in humans. In model systems, long GAA/TTC
      tracts also act as chromosomal fragile sites that can trigger gross chromosomal
      rearrangements. The mechanisms that regulate the metabolism of GAA/TTC repeats
      are poorly understood. We have developed an experimental system in the yeast
      Saccharomyces cerevisiae that allows us to systematically identify genes crucial
      for maintaining the repeat stability. Two major groups of mutants defective in
      DNA replication or transcription initiation are found to be prone to fragility
      and large-scale expansions. We demonstrate that problems imposed by the repeats
      during DNA replication in actively dividing cells and during transcription
      initiation in nondividing cells can culminate in genome instability. We propose
      that similar mechanisms can mediate detrimental metabolism of GAA/TTC tracts in
      human cells.

PMID- 22959271
TI  - The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy.
AB  - Cells continually assess their energy and nutrient state to maintain growth and
      survival and engage necessary homeostatic mechanisms. Cell-autonomous responses
      to the fed state require the surveillance of the availability of amino acids and
      other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates
      information on nutrient and amino acid availability to support protein synthesis
      and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a
      direct sensor of the fed state and amino acid availability. Knocking down this
      receptor, which is found in most tissues, reduces the ability of amino acids to
      signal to mTORC1. Interfering with this receptor alters localization of mTORC1,
      downregulates expression of pathway inhibitors, upregulates key amino acid
      transporters, blocks translation initiation, and induces autophagy. These
      findings reveal a mechanism for communicating amino acid availability through a
      GPCR to mTORC1 in mammals.

PMID- 22959272
TI  - Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune
      signaling and cytokine production.
AB  - Innate immunity controls pathogen replication and spread. Yet, certain pathogens,
      such as Hepatitis C Virus (HCV), escape immune elimination and establish
      persistent infections that promote chronic inflammation and related diseases.
      Whereas HCV regulatory proteins that attenuate antiviral responses are known,
      those that promote inflammation and liver injury remain to be identified. Here,
      we show that transient expression of HCV RNA-dependent RNA polymerase (RdRp),
      NS5B, in mouse liver and human hepatocytes results in production of small RNA
      species that activate innate immune signaling via TBK1-IRF3 and NF-kappaB and
      induce cytokine production, including type I interferons (IFN) and IL-6. NS5B
      expression also results in liver damage.

PMID- 22959273
TI  - Long noncoding RNAs with snoRNA ends.
AB  - We describe the discovery of sno-lncRNAs, a class of nuclear-enriched intron
      derived long noncoding RNAs (lncRNAs) that are processed on both ends by the
      snoRNA machinery. During exonucleolytic trimming, the sequences between the
      snoRNAs are not degraded, leading to the accumulation of lncRNAs flanked by
      snoRNA sequences but lacking 5' caps and 3' poly(A) tails. Such RNAs are widely
      expressed in cells and tissues and can be produced by either box C/D or box H/ACA
      snoRNAs. Importantly, the genomic region encoding one abundant class of sno
      lncRNAs (15q11-q13) is specifically deleted in Prader-Willi Syndrome (PWS). The
      PWS region sno-lncRNAs do not colocalize with nucleoli or Cajal bodies, but
      rather accumulate near their sites of synthesis. These sno-lncRNAs associate
      strongly with Fox family splicing regulators and alter patterns of splicing.
      These results thus implicate a previously unannotated class of lncRNAs in the
      molecular pathogenesis of PWS.

PMID- 22959274
TI  - Failure of amino acid homeostasis causes cell death following proteasome
      inhibition.
AB  - The ubiquitin-proteasome system targets many cellular proteins for degradation
      and thereby controls most cellular processes. Although it is well established
      that proteasome inhibition is lethal, the underlying mechanism is unknown. Here,
      we show that proteasome inhibition results in a lethal amino acid shortage. In
      yeast, mammalian cells, and flies, the deleterious consequences of proteasome
      inhibition are rescued by amino acid supplementation. In all three systems, this
      rescuing effect occurs without noticeable changes in the levels of proteasome
      substrates. In mammalian cells, the amino acid scarcity resulting from proteasome
      inhibition is the signal that causes induction of both the integrated stress
      response and autophagy, in an unsuccessful attempt to replenish the pool of
      intracellular amino acids. These results reveal that cells can tolerate protein
      waste, but not the amino acid scarcity resulting from proteasome inhibition.

PMID- 22959276
TI  - Suggested modification for the proposed clinical classification on OSMF.

PMID- 22959275
TI  - LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor
      abundance.
AB  - LIN28 is a conserved RNA-binding protein implicated in pluripotency,
      reprogramming, and oncogenesis. It was previously shown to act primarily by
      blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles
      of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through
      crosslinking and immunoprecipitation coupled with high-throughput sequencing
      (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous
      LIN28, we have defined discrete LIN28-binding sites in a quarter of human
      transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched
      within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA
      precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation
      and also direct but differing effects on the protein abundance of splicing
      regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays
      demonstrated that exogenous LIN28 expression causes widespread downstream
      alternative splicing changes. These findings identify important regulatory
      functions of LIN28 via direct mRNA interactions.

PMID- 22959279
TI  - Solutions to replace quantity with quality in science.

PMID- 22959277
TI  - The role of 18F-FDG PET/CT metabolic tumour volume in predicting survival in
      patients with metastatic nasopharyngeal carcinoma.
AB  - OBJECTIVES: To investigate the role of PET-derived imaging markers in predicting
      metastatic nasopharyngeal carcinoma (NPC) outcomes. MATERIALS AND METHODS: A
      total of 56 patients with metastatic NPC were enrolled. Before treatment, all of
      the participants underwent (18)F-FDG PET/CT. The following (18)F-FDG PET
      parameters were assessed: standardised uptake value, metabolic tumour volume
      (MTV), and total lesion glycolysis. Multivariate Cox proportional hazards models
      were used to identify the independent predictors of survival. RESULTS: The
      multivariate analysis showed that performance status>1 (P=0.007), Epstein-Barr
      virus (EBV) DNA titre>5000 copies/mL (P=0.001), and MTV>110 mL (P=0.013) were
      independent risk factors for progression-free survival (PFS). Male sex (P=0.004),
      performance status>1 (P<0.0001), EBV DNA level>5000 copies/mL (P<0.0001), and
      MTV>110 mL (P=0.003) independently predicted overall survival (OS). The 2-year
      PFS and OS rates of the patients with MTV<=110 mL were 23.2% and 43%,
      respectively, compared with 0% and 9.1%, respectively, for those with MTV>110 mL.
      Combining the MTV with the EBV DNA titre allowed further survival stratification
      by dividing the patients into three groups with distinct PFS (2-year rates=30.8%,
      7.1%, and 0%, P<0.0001) and OS (2-year rates=68.4%, 40%, and 0%, P<0.0001) rates.
      CONCLUSION: The MTV appears to be an independent risk factor in metastatic NPC
      patients. This factor is complementary to the EBV DNA titre for predicting
      survival in metastatic NPC.

PMID- 22959278
TI  - Pattern discovery from patient controlled analgesia demand behavior.
AB  - Unlike previous research on patient controlled analgesia, this study explores
      patient demand behavior over time. We apply clustering methods to disclose demand
      patterns among patients over the first 24h of analgesic medication after surgery.
      We consider demographic, biomedical, and surgery-related data in statistical
      analyses to determine predictors for patient demand behavior, and use stepwise
      regression and Bayes risk analysis to evaluate the influence of demand pattern on
      analgesic requirements. We identify three demand patterns from 1655 patient
      controlled analgesia request log files. Statistical tests show correlations of
      gender (p=.0022), diastolic blood pressure (p=.025), surgery type (p=.0028), and
      surgical duration (p<.0095) with demand patterns. Stepwise regression and Bayes
      risk analysis show demand pattern plays the most important role in analgesic
      consumption prediction (p=0.E+0). This study suggests analgesia request patterns
      over time exist among patients, and clustering can disclose demand behavioral
      patterns.

PMID- 22959280
TI  - [French Society of STomatology and Maxillo-facial Surgery: the mutation].

PMID- 22959281
TI  - Hip fracture discrimination from dual-energy X-ray absorptiometry by statistical
      model registration.
AB  - Although the areal Bone Mineral Density (BMD) measurements from dual-energy X-ray
      absorptiometry (DXA) are able to discriminate between hip fracture cases and
      controls, the femoral strength is largely determined by the 3D bone structure. In
      a previous work a statistical model was presented which parameterizes the 3D
      shape and BMD distribution of the proximal femur. In this study the parameter
      values resulting from the registration of the model onto DXA images are evaluated
      for their hip fracture discrimination ability with respect to regular DXA derived
      areal BMD measurements. The statistical model was constructed from a large
      database of QCT scans of females with an average age of 67.8 +/- 17.0 years. This
      model was subsequently registered onto the DXA images of a fracture and control
      group. The fracture group consisted of 175 female patients with an average age of
      66.4 +/- 9.9 years who suffered a fracture on the contra lateral femur. The
      control group consisted of 175 female subjects with an average age of 65.3 +/-
      10.0 years and no fracture history. The discrimination ability of the resulting
      model parameter values, as well as the areal BMD measurements extracted from the
      DXA images were evaluated using a logistic regression analysis. The area under
      the receiver operating curve (AUC) of the combined model parameters and areal BMD
      values was 0.840 (95% CI 0.799-0.881), whilst using only the areal BMD values
      resulted in an AUC of 0.802 (95% CI 0.757-0.848). These results indicate that the
      discrimination ability of the areal BMD values is improved by supplementing them
      with the model parameter values, which give a more complete representation of the
      subject specific shape and internal bone distribution. Thus, the presented method
      potentially allows for an improved hip fracture risk estimation whilst
      maintaining DXA as the current standard modality.

PMID- 22959282
TI  - British adults with chronic health conditions or impairments face significant
      barriers to accessing health services.
AB  - OBJECTIVES: To quantify the extent to which adults with chronic health conditions
      or impairments in Great Britain experience barriers to accessing health services
      in comparison to adults without impairments. STUDY DESIGN: Secondary analysis of
      cross-sectional population-based survey data from the Life Opportunities Survey.
      METHODS: The Life Opportunities Survey interviewed a nationally representative
      sample of 37,513 individuals age 16 or older from 19,951 households. A subset of
      questions addressed disability status, health conditions and impairments, and
      participation restrictions in accessing public services. Simple bivariate and
      multivariate logistic regression (controlling for age, gender, and ethnicity)
      analyses were undertaken to estimate the risk that specific condition/impairment
      types were associated with barriers to accessing health care. RESULTS:
      Individuals with chronic health conditions or impairments were significantly more
      likely to report difficulties accessing health care services. Additionally,
      individuals in each condition/impairment group had significantly higher odds of
      experiencing a variety of barriers, including discrimination by healthcare staff,
      inexperienced or unhelpful staff, lack of help with communication, lack of
      information, problems with transportation, difficulty getting into buildings,
      difficulty using facilities, and lack of confidence or anxiety. CONCLUSIONS:
      Individuals with chronic health conditions or impairments are significantly more
      likely than their non-impaired peers to experience barriers in accessing health
      care. These barriers are likely to exacerbate disability and may increase the
      likelihood of developing additional preventable health conditions. As a result,
      they may contribute towards the health inequalities experienced by disabled
      people. The existence of these barriers also suggests that health care provision
      in Great Britain is failing to meet its statutory requirement to provide
      'reasonable adjustments' to ensure equality of access for disabled adults.

PMID- 22959283
TI  - The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil
      and the cholinergic precursor choline alphoscerate in Alzheimer's disease with
      cerebrovascular injury: interim results.
AB  - BACKGROUND: Cholinesterase inhibitors (ChE-Is) are among the drugs more largely
      used for the treatment of mild-to-moderate symptoms of Alzheimer's disease (AD),
      but beneficial long-term effects of these compounds on the cognitive, functional,
      and behavioural symptoms of the disease are small and not always apparent in
      practice. Preclinical investigations have suggested that association between ChE
      Is and the cholinergic precursor choline alphoscerate enhances cholinergic
      neurotransmission more effectively than single compounds alone. The ongoing
      clinical trial on the "Effect of association between a ChE-I and choline
      alphoscerate on cognitive deficits in Alzheimer's disease associated with
      cerebrovascular injury" (ASCOMALVA) was designed to assess if association of the
      ChE-I donepezil with choline alphoscerate has a more favourable clinical profile
      than monotherapy with donepezil alone. METHODS: ASCOMALVA is a double-blind
      multicentre trial that has completed the first 12 months of observation of 91
      patients of the 210 planned. Patients were aged between 56 and 91 years (mean 75
      +/- 10 years) and were included in the protocol with a MMSE score between 15 and
      24. Patients with AD diagnosed according to the DSM IV criteria suffer from
      ischemic brain damage documented by neuroimaging (MRI and CT scan), with a
      score>=2 in at least one subfield of the New Rating Scale for Age-Related White
      Matter Changes (ARWMC). Patients were randomly allotted to an active treatment
      group (donepezil+choline alphoscerate) or to a reference treatment group
      (donepezil+placebo) and were examined after 3, 6, 9 and 12 months of treatment.
      RESULTS: Cognitive functions, patient's daily activities and behavioural symptoms
      were assessed by the Mini-Mental State Evaluation (MMSE), Alzheimer's Disease
      Assessment Scale Cognitive subscale (ADAS-cog), Basic Activities of Daily Living
      (BADL), Instrumental Activities of Daily Living (IADL) and Neuropsychiatric
      Inventory (NPI), of severity and of caregiver distress measures (NPI-F and NPI
      D). Patients of the reference group (donepezil+placebo) showed along the course
      of the 12months of observation, a slight time-dependent worsening of MMSE, ADAS
      cog, IADL and NPI-D scores and no changes in the BADL and NPI-F scores. Donepezil
      plus choline alphoscerate improved compared to donepezil alone the different
      items analysed except the BADL. CONCLUSIONS: The first results of the ASCOMALVA
      trial suggest that association of choline alphoscerate to the standard treatment
      with a ChE-I may represent an option to prolong beneficial effects of cholinergic
      therapies in AD with concomitant ischemic cerebrovascular injury.

PMID- 22959284
TI  - Prognostic and clinical implication of a disintegrin and metalloprotease 8
      expression in pediatric medulloblastoma.
AB  - AIM: To investigate the expression patterns and clinical value of a disintegrin
      and metalloprotease 8 (ADAM8) in pediatric medulloblastoma. METHODS: We evaluated
      the expression of ADAM8 mRNA and protein in pediatric medulloblastoma tissues by
      Quantitative RT-PCR, Western blot analysis and Immunohistochemical staining,
      respectively. The correlation of ADAM8 immunostaining with clinical-pathological
      features of medulloblastoma patients and its prognostic relevance were further
      determined. RESULTS: ADAM8 mRNA and protein were both most highly expressed in
      medulloblastoma tissues when compared with normal cerebellum tissues (both
      P<0.001). According to the immunohistochemisty analysis, we found statistically
      significant correlations of high ADAM8 protein expression with advanced
      metastatic stage (P=0.01), aggressive histopathological type (P=0.006), as well
      as with undifferentiated tumor (P=0.02). We further determined a statistically
      significant association between ADAM8 protein expression and clinical outcome of
      medulloblastoma patients, with higher expression levels of ADAM8 associating with
      a worse overall survival (P=0.02). CONCLUSION: Our results provide the first
      evidence that the up-regulation of ADAM8 in medulloblastoma tissues might be
      correlated with the advanced tumor progression and poor prognosis of patients
      with this disease. Detection of ADAM8 expression might facilitate the prognostic
      assessment and improve the therapeutic strategy for medulloblastoma patients.

PMID- 22959285
TI  - [Low-pressure tamponade mimicking cholecystitis].
AB  - Low-pressure tamponade is rare and little known with difficult clinical
      recognition. We report a case of this pathology in a patient admitted for
      abdominal severe sepsis. Pericardiocentesis led to identification of Salmonella
      typhimurium pericarditis. This case report emphasizes the clinical recognition
      difficulty and the interest of early fast echography in case of hemodynamic
      emergency.

PMID- 22959286
TI  - A T-cell epitope on NS3 non-structural protein enhances the B and T cell
      responses elicited by dendrimeric constructions against CSFV in domestic pigs.
AB  - It has been recently reported by our group that dendrimeric constructs combining
      B- and T-cell epitopes from classical swine fever virus (CSFV) provided partial
      protection against experimental infection. This research evaluated four newly
      designed constructions while taking into account our previous work, including the
      direct implication that a T-cell epitope from the NS3 protein contributes to the
      generation of the immune response against CSFV. To this end, the dendrimeric
      constructions, including either this NS3 T-cell epitope alone or two different B
      cell epitopes without this T-cell epitope, were used to immunise pigs. Thus,
      construct 1, containing the NS3 T-cell epitope and four copies of a previously
      described B-cell epitope, significantly reduced the clinical scores and RNA viral
      loads after challenge relative to the control group. In three out of six animals
      in this group, vaccination achieved partial protection and was associated with
      IFN-gamma producing-cells and neutralising antibodies. In contrast, the pigs
      immunised with construct 2, again with four copies of the B epitope of construct
      1 but lacking the T-cell motif, developed more severe clinical signs. Finally,
      the additional constructs 3 and 4 included four copies of a B epitope that was
      different from the epitope used in constructs 1 and 2 with or without the
      abovementioned NS3 T-cell epitope, respectively. Pigs immunised with these latter
      constructs developed low levels of peptide-specific antibodies that correlated
      with equally low levels of cellular responses, an absence of neutralising
      antibodies and a lack of protection. Even so, the clinical scores in the first
      week after the challenge were less severe for animals vaccinated with construct 3
      than for those given construct 4. Our results confirm the relevant role of the B
      cell epitope in residues 694-712 of the glycoprotein E2 (which is used in both
      constructs 1 and 2) for protection against CSFV, as well as the appropriateness
      of the newly used NS3 peptide as a specific T-cell epitope in domestic pigs.

PMID- 22959287
TI  - Survival after C-arm CT-assisted chemoembolization of unresectable hepatocellular
      carcinoma.
AB  - PURPOSE: To compare patient survival after transarterial chemoembolization with
      and without intraprocedural C-arm computed tomography (CT) in patients with
      unresectable hepatocellular carcinoma. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 130 patients with unresectable hepatocellular carcinoma
      who underwent lipiodol-based chemoembolization using a C-arm cone-beam system. We
      compared patients who underwent chemoembolization with angiography alone (69
      patients; April 2005-July 2007) to those who underwent C-arm CT-assisted
      chemoembolization (61 patients; July 2007-April 2010). Overall and local
      progression-free survivals were compared using the Kaplan-Meier estimator with
      log-rank testing. Univariate and multivariate analyses were performed using the
      Cox proportional hazards model. RESULTS: Overall survival rates of patients who
      underwent chemoembolization with and without C-arm CT assistance were 94% and
      79%, 81% and 65%, and 71% and 44% at 1, 2, and 3 years, respectively. Local
      progression-free survival rates of these patients were 43% and 27%, 31% and 10%,
      and 26% and 5% at 1, 2, and 3 years, respectively. Patients receiving C-arm CT
      assisted chemoembolization had significantly higher overall (P=0.005) and local
      progression-free (P=0.003) survival rates than those receiving chemoembolization
      with angiography alone. Multivariate analysis showed that C-arm CT assistance was
      an independent factor associated with longer overall survival (hazard ratio,
      0.40; P=0.033) and local progression-free survival (hazard ratio, 0.25; P=0.003).
      CONCLUSION: C-arm CT usage in addition to angiography during transarterial
      chemoembolization prolongs survival in patients with unresectable hepatocellular
      carcinoma.

PMID- 22959288
TI  - Extrapleural harvesting of the mammary artery in the costodiaphragmatic sulcus.
AB  - In coronary artery bypass surgery the most commonly used conduit for grafting the
      left anterior descending artery is the left internal mammary artery. In
      harvesting the internal mammary artery the parietal pleura is frequently
      breached. This is associated with increased post operative complications. The
      diaphragm is not in contact with the parietal pleura anteriorly. The risk of
      opening the pleura is considerably reduced if the costodiaphragmatic sulcus is
      developed first. If more cardiac surgeons were aware of the potential of the
      costodiaphragmatic sulcus then some of the complications associated with coronary
      artery surgery could be reduced. 

PMID- 22959290
TI  - The initial year.

PMID- 22959289
TI  - Finding fault: causality and counterfactuals in group attributions.
AB  - Attributions of responsibility play a critical role in many group interactions.
      This paper explores the role of causal and counterfactual reasoning in blame
      attributions in groups. We develop a general framework that builds on the notion
      of pivotality: an agent is pivotal if she could have changed the group outcome by
      acting differently. In three experiments we test successive refinements of this
      notion - whether an agent is pivotal in close possible situations and the number
      of paths to achieve pivotality. In order to discriminate between potential
      models, we introduced group tasks with asymmetric structures. Some group members
      were complements (for the two to contribute to the group outcome it was necessary
      that both succeed) whereas others were substitutes (for the two to contribute to
      the group outcome it was sufficient that one succeeds). Across all three
      experiments we found that people's attributions were sensitive to the number of
      paths to pivotality. In particular, an agent incurred more blame for a team loss
      in the presence of a successful complementary peer than in the presence of a
      successful substitute.

PMID- 22959291
TI  - Chronic anterior dislocation of the shoulder.
AB  - The treatment of 17 chronic, unreduced anterior dislocations of the shoulder was
      reviewed. Eleven women and six men with on average age of 67 years (range 36 to
      88 years) were studied. The duration of dislocation averaged 2.3 years (8 weeks
      to 8 years). Seven patients were treated without surgery despite severe
      functional deficits, for reasons of health or motivation. Ten were treated with
      surgery. One patient with preserved joint surfaces underwent open reduction and
      corticoid transfer to bone graft an eroded anterior glenoid. Nine patients with
      destroyed articular surfaces underwent unconstrained replacement orthroplosty.
      Humeral retroversion was increased for stability. The soft tissues were
      reattached, and rehabilitation was modified as with a repair of recurrent
      dislocations. Anterior glenoid erosion was often present and required bone
      grafting to support the glenoid component in four shoulders. Two chronic rotator
      cuff tears required repair. Nine patients were followed from 2 to 6 years, with
      an average of 3.9 years. The results were four excellent, four satisfactory, and
      one unsatisfactory. Although the reconstruction is complex, the surgical results
      were clearly superior to those of the nonoperative group.

PMID- 22959292
TI  - Posttraumatic changes of the proximal humerus: Malunion, nonunion, and
      osteonecrosis. Treatment with modular hemiarthroplasty or total shoulder
      arthroplasty.
AB  - Since 1986, 20 shoulder orthroplasties have been performed for chronic,
      posttroumatic changes of the proximal humerus with a modular prosthetic system.
      The average patient follow-up was 33 months, range 24 to 47 months. Sixteen women
      and four men with an average age of 69.6 years were studied. The procedure was
      carried out for malunion of the tuberosities or humeral head in eight patients,
      nonunion of the humeral head in six patients, osteonecrosis in three patients,
      and chronic impression fractures associated with dislocations of the humeral head
      in three patients. Fair, good, or excellent results were achieved in 90% of
      patients. The average postoperative motions were forward elevation, 111 degrees ;
      external rotation, 30 degrees ; and internal rotation to L2. Two failures
      occurred. One patient had nonunion of a tuberosity repair with superior
      instability and secondary impingement requiring revision surgery. A second
      patient had a postoperative neuropothy and posterior subluxotion with poor
      function. Patients younger than 70 years of age and those who did not require
      tuberosity osteotomy had better results. The success of orthroplasty in these
      difficult occurrences is dependent upon appropriate patient selection, extensive
      preoperative evaluation, strict attention to surgical detail, and postoperative
      rehabilitation. Avoidance of tuberosity osteotomy, when feasible, is advised. A
      modular design has advantages because it facilitates soft-tissue tensioning and
      tuberosity repair.

PMID- 22959293
TI  - Ultrasonography of the rotator cuff: Analysis of results in a community setting.
AB  - Forty-six patients underwent ultrasonogrophy evaluation of their shoulder for
      suspected rotator cuff tears from 1989 to 1992. All ultrasound studies were
      evaluated by a radiologist (HJH) who was not subspecialty-trained in shoulder
      ultrasonography. All patients had surgical confirmation of the status of their
      tendons. A statistical analysis of the accuracy of ultrasound in detecting
      rotator cuff tearing was performed. The sensitivity was 81%, and the specificity
      was 100%; there was a positive predictive value of 100% and a negative predictive
      value of 71%. Using strict sonographic criteria for diagnosing a rotator cuff
      tear, we conclude that ultrasound can detect intermediate or large rotator cuff
      tears with great accuracy (19 of 20 shoulders). Accuracy decreases dramatically
      in the presence of a small tear (six of 11 shoulders). At our hospital the cost
      of ultrasound examination of the shoulder is 0.19 the cost of magnetic resonance
      imaging of the shoulder and is 0.62 the cost of a shoulder arthrogrom. Ultrasound
      of the shoulder should be considered for imaging the rotator cuff because of its
      accuracy, low cost, and high patient satisfaction. It can be reliably performed
      by radiologists with state-of-the-art equipment who are interested in and have
      experience with the procedure.

PMID- 22959294
TI  - Glenohumeral stability from concavity-compression: A quantitative analysis.
AB  - The purpose of this research was to determine the degree to which compression of
      the humeral head into the glenoid concavity stabilizes it against translating
      forces. Ten normal fresh-frozen cadaver glenohumeral joints in which the labrum
      was preserved were used. A compressive load of 50 N was applied to the humeral
      head in a direction perpendicular to the glenoid surface. Increasing tangential
      forces were then applied until the head dislocated over the glenoid lip. The
      tangential force at dislocation was examined for eight different directions, 45
      degrees  apart around the glenoid. Concavity-compression stability was then
      examined for an increased compressive load of 100 N. Finally, the protocol with
      50 and 100 N of compressive load was repeated after the glenoid labrum was
      excised. Concavity-compression of the humeral head into the glenoid is a most
      efficient stabilizing mechanism. With the labrum intact the humeral head resisted
      tangential forces of up to 60% of the compressive load. The degree of compression
      stabilization varied around the circumference of the glenoid with the greatest
      magnitude superiorly and inferiorly. This may be attributed to the greater
      glenoid depth in these directions. Resection of the glenoid labrum reduced the
      effectiveness of compression stabilization by approximately 20%. These results
      indicate that concavity-compression may be an important mechanism for providing
      stability in the mid-range of glenohumeral motion where the capsule and ligaments
      are lax. The effectiveness is enhanced by the presence of an intact glenoid
      labrum.

PMID- 22959295
TI  - Shoulder manipulation in patients with adhesive capsulitis and diabetes mellitus:
      A clinical note.
AB  - Five patients with diabetes mellitus and six affected shoulders underwent 10
      manipulations under general anesthesia. During the postmanipulotion course the
      gains in motion made at the time of manipulation and the relief of pain achieved
      began to diminish at 2 weeks, gradually returning to premanipulation levels at 4
      weeks. The level of pain and the limitation of motion continued during the entire
      period of follow-up, averaging 8 months. In these patients manipulation had no
      effect on the course of the adhesive copsulitis.

PMID- 22959296
TI  - Avulsion fracture of the scapular spine: A case report.
AB  - Fractures of the scapula are infrequent injuries usually associated with direct,
      violent trauma to the shoulder girdle. We present a rare case of an avulsion
      fracture of the scapular spine occurring in a patient during a game of badminton.
      Open reduction and internal fixation with a tension band-wiring technique was
      performed. The patient had an uncomplicated recovery and rapidly returned to
      sporting activity.

PMID- 22959297
TI  - Isolated avulsion fracture of the lesser tuberosity of the humerus: A case
      report.
AB  - Isolated avulsion fracture of the lesser tuberosity of the humerus is extremely
      rare. Only 75 cases have been reported in the literature since Hartigan's report
      in 7895. In all of the previously reported cases, these injuries seriously
      impaired the patients' ability to function. However, the case reported here
      involves chronic pain after an avulsion fracture of a fragment of the lesser
      tuberosity of the humerus in a young male athlete. This patient continued to
      participate in competitive athletics for over a year after his injury before he
      sought definitive treatment. Eventually, surgical excision of the fragment of
      lesser tuberosity relieved the patient's symptoms.

PMID- 22959298
TI  - The glenoid component in total shoulder arthroplasty.

PMID- 22959300
TI  - Origin and differentiation of ionocytes in gill epithelium of teleost fish.
AB  - This paper focuses on the environmental cues that transform the gills of
      euryhaline teleost fish from an oxygen exchange structure into a bifunctional
      organ that can control both gaseous movement and water/ion transport. The
      cellular development that allows this structure to accomplish these tasks begins
      shortly after fertilization of the egg. It involves alterations of structure and
      function of embryonic cells [ionoblasts (IB)] that are shed from the pharyngeal
      anlage area of the embryo. These IB contain unique protein-receptor domains in
      the plasma membrane. These receptors respond specifically to the environmental
      cues effecting a calcium-binding protein receptor [calcium-sensing receptor
      (CaSR)]. The CaSR containing IB act as stem cells and are acted upon by isotocin,
      a heteroprotein regulator which induces them to form progenitor ionocytes (pIC).
      The pIC form two types of cells. The first type becomes an aquaphilic ionocyte
      which regulates uptake of ions and through aquaporin molecules transports water
      out of the cell and controls body fluids of the fish. This mechanism is essential
      for freshwater living. The second type becomes a halophilic ionocyte and
      transports ions out of the cell and controls cell shrinkage by uptake of water
      via aquaporin molecules. This mechanism is essential for seawater living. These
      differentiating events in the pIC are controlled by the cross talking of genomic
      mechanisms found in the precursor IB. To unravel the cross talking events it is
      necessary to uncover how these genetic pathways are regulated by transcriptional
      and translational events coming from complementary DNA. Various gene families are
      involved such as those found in apoptosis mechanisms, regulatory volume
      regulators and ionic transport systems (cystic fibrosis transmembrane conductance
      regulator).

PMID- 22959299
TI  - The effect of oral contraceptives on current wheezing in young women.
AB  - BACKGROUND: Emerging evidence suggests that sex steroid hormones may influence
      respiratory symptoms. The existing literature about the role of oral
      contraceptive pill (OCP) on respiratory disease is scarce and conflicting
      especially during the adolescent period. In this study, we aimed to investigate
      the effect of OCPs on current wheezing among adolescents and young adults.
      METHODS: A questionnaire was administered face-to-face to adolescents and young
      women by a physician. The questionnaire included ISAAC survey-comprised questions
      on ever wheezing, current wheezing, allergic diseases, smoking history (active or
      passive), and family history of allergic diseases and questions on OCP usage
      status. The effect of OCPs on wheezing was evaluated by logistic regression
      analysis. RESULTS: A total of 487 subjects aged between 11.3 and 25.6years
      participated in the study and 196 (40.2%) reported that they had used OCPs. 7.4%
      of the participants had physician-diagnosed asthma and 10.3% of them were active
      smokers. It was detected that OCPs were associated with increased risk for
      current wheezing (odds ratio, 2.36; 95% CI, 1.25-4.47 adjusted for asthma and
      current smoker) and this risk was related with the usage during the past year.
      CONCLUSION: Young women taking oral contraceptives had a higher rate of current
      wheezing, suggesting that sex steroids may be of importance for respiratory
      health.

PMID- 22959301
TI  - Cellular mechanisms for the biogenesis and transport of synaptic and dense-core
      vesicles.
AB  - The release of intercellular messengers from synaptic (SVs) and dense-core
      vesicles (DCVs) constitutes the primary mechanism for communication between
      neighboring or distant cells and organs in response to stimuli. Here we review
      the life span of SVs and DCVs found in the brain, neuroendocrine and exocrine
      tissues. These vesicles must be formed, trafficked, and their contents secreted;
      processes which require orchestrated actions of a great repertoire of lipids,
      proteins, and enzymes. For biogenesis and vesicular budding, lipids that
      influence curvature and aggregation of cargo are necessary for pinching off of
      vesicles. Vesicles travel on cytoskeletal filaments powered by motors that
      control the dynamics: location, speed, and directionality of movement. Regardless
      of mechanisms of traffic, vesicles arrive at sites of release and are docked for
      exocytosis, followed by membrane fusion, and release of vesicular content to
      exert physiological responses. Neurological disorders with pathology involving
      abnormal vesicular budding, trafficking, or secretion are discussed.

PMID- 22959302
TI  - Effect of viral infection on the nuclear envelope and nuclear pore complex.
AB  - The nuclear envelope (NE) is a vital structure that separates the nucleus from
      the cytoplasm. Because the NE is such a critical cellular barrier, many viral
      pathogens have evolved to modulate its permeability. They do this either by
      breaching the NE or by disrupting the integrity and functionality of the nuclear
      pore complex (NPC). Viruses modulate NE permeability for different reasons. Some
      viruses disrupt NE to deliver the viral genome into the nucleus for replication,
      while others cause NE disruption during nuclear egress of newly assembled
      capsids. Yet, other viruses modulate NE permeability and affect the
      compartmentalization of host proteins or block the nuclear transport of host
      proteins involved in the host antiviral response. Recent scientific advances
      demonstrated that other viruses use proteins of the NPC for viral assembly or
      disassembly. Here we review the ways in which various viruses affect NE and NPC
      during infection.

PMID- 22959303
TI  - New insights into cell cycle regulation and DNA damage response in embryonic stem
      cells.
AB  - Embryonic stem cells (ESCs) have unlimited proliferative potential, while
      retaining the ability to differentiate into descendants of all three embryonic
      layers. High proliferation rate of ESCs is accompanied by a shortening of the
      G(1) phase and the lack of G(1) checkpoint following DNA damage. The absence of
      G(1) arrest in ESCs after DNA damage is likely caused by a dysfunction of the p53
      dependent p21Waf1 pathway that is a key event for the maintenance of
      pluripotency. There are controversial data on the functional status of p53, but
      it is well established that one of the key p53 target-p21Waf1-is expressed in
      ESCs at a very low level. Despite the lack of G(1) checkpoint, ESCs are capable
      to repair DNA defects; moreover the DNA damage response (DDR) signaling operates
      very effectively throughout the cell cycle. This review covers also the results
      obtained with the reprogramming of somatic cells into the induced pluripotent
      stem cells, for which have been shown that a partial dysfunction of the p53Waf1
      pathway increases the frequency of generation of pluripotent cells. In summary,
      these results indicate that the G(1) checkpoint control and DDR are distinct from
      somatic cells and their status is tightly connected with maintaining of
      pluripotency and self-renewal.

PMID- 22959304
TI  - Angiogenic effects of erythropoietin.
AB  - Erythropoietin (Epo) is a low-molecular weight glycoprotein hormone stimulator of
      erythropoiesis synthesized in the fetal liver and in the adult kidney. Moreover,
      Epo is a pleiotropic cytokine that exerts diverse biological effects in non
      hematopoietic tissues, and angiogenesis is indicated as one of its extra
      hematopoietic functions. The involvement of Epo in angiogenesis may be considered
      as subset of its role in improving overall tissue oxygenation and of its anti
      apoptotic role. In this context, Epo may be considered as an endogenous
      stimulator of vessel growth during tumor progression, and inhibition of Epo
      signaling might be suggested as a new antiangiogenic therapeutic approach. It is
      conceivable suppose that the effect of Epo is multifactorial, depending on the
      type of tumor and level of functionality of Epo receptor expression in tumor
      cells, as well as on other variables, such as hypoxic stress and degree of
      anemia.

PMID- 22959305
TI  - Radiation responses and resistance.
AB  - The cytotoxic effect of ionizing radiation makes it a popular therapeutic tool
      against cancer. It is, however, a double-edged sword. Radiation exposure
      unleashes a plethora of protective and survival mechanisms that include increased
      proliferation, remodeling of the vasculature and altered cell motility. These
      mechanisms can play a pro-survival role in remaining cells, contributing to
      repopulation of tumors after radiation treatment. Understanding these mechanisms
      and finding ways to minimize their impact would improve the outcome of
      radiotherapy.

PMID- 22959306
TI  - Effects of ethanol exposure on nervous system development in zebrafish.
AB  - Alcohol (ethanol) is a teratogen that adversely affects nervous system
      development in a wide range of animal species. In humans numerous congenital
      abnormalities arise as a result of fetal alcohol exposure, leading to a spectrum
      of disorders referred to as fetal alcohol spectrum disorder (FASD). These
      abnormalities include craniofacial defects as well as neurological defects that
      affect a variety of behaviors. These human FASD phenotypes are reproduced in the
      rodent central nervous system (CNS) following prenatal ethanol exposure. While
      the study of ethanol effects on zebrafish development has been more limited,
      several studies have shown that different strains of zebrafish exhibit
      differential susceptibility to ethanol-induced cyclopia, as well as behavioral
      deficits. Molecular mechanisms underlying the effects of ethanol on CNS
      development also appear to be shared between rodent and zebrafish. Thus,
      zebrafish appear to recapitulate the observed effects of ethanol on human and
      mouse CNS development, indicating that zebrafish can serve as a complimentary
      developmental model system to study the molecular basis of FASD. Recent studies
      examining the effect of ethanol exposure on zebrafish nervous system development
      are reviewed, with an emphasis on attempts to elucidate possible molecular
      pathways that may be impacted by developmental ethanol exposure. Recent work from
      our laboratories supports a role for perturbed extracellular matrix function in
      the pathology of ethanol exposure during zebrafish CNS development. The use of
      the zebrafish model to assess the effects of ethanol exposure on adult nervous
      system function as manifested by changes in zebrafish behavior is also discussed.

PMID- 22959307
TI  - Elbow reconstruction with a pedicled thoracodorsal artery perforator flap after
      excision of an upper-extremity giant hairy nevus.
AB  - The complexity of managing large soft-tissue defects at the elbow region by
      conventional techniques arises from the difficulty of providing sufficient tissue
      with adequate elasticity and durability. Reconstruction options that allow early
      mobilisation and avoid the risk of functional loss should be considered to
      achieve defect closure at the elbow region. A 21-year-old man presented with a
      congenital giant hairy nevus on his left upper extremity. The nevus was excised
      and the resulting raw surface after the excision was covered with a split
      thickness skin graft except for the elbow region. The elbow was covered in one
      stage with an ipsilateral 24 cm long pedicled thoracodorsal artery perforator
      (TDAP) flap. The follow-up examination 3 years after total reconstruction
      demonstrated durable elbow support provided by the TDAP flap. The patient
      revealed no complaint considering pain or sensitivity even when exposed to
      mechanical stress. Split-thickness skin grafting of the large superficial defects
      is almost always possible; however, impairment of the function on joint areas due
      to gradual contraction and skin graft propensity to ulcers under mechanical
      stresses can be devastating. The elbow is a weight-bearing area of the body.
      Elbow defects require durable and thin soft-tissue coverage and the tissue cover
      must possess excellent elastic properties to re-establish elbow mobility. The
      TDAP flap is an ideal choice for elbow soft-tissue defects. The longest pedicle
      length reported for the TDAP flap is 23 cm. In our case, the pedicle length was
      24 cm and it was possible to transfer this flap to the elbow on its pedicle. A
      pedicled TDAP skin flap so as to provide elbow coverage in one stage is a useful
      choice to retain in one's armamentarium.

PMID- 22959308
TI  - Progress made in the reprogramming field: new factors, new strategies and a new
      outlook.
AB  - The ground-breaking work of Yamanaka and Thomson showed that forced expression of
      just four transcription factors can reprogram mouse and human somatic cells to
      pluripotency, leading to the discovery of the so-called induced pluripotent stem
      cells (iPSCs). Similar to embryonic stem cells (ESCs), iPSCs have the ability to
      permanently self-renew and also give rise to multiple cell types once
      differentiated. These cells opened up the opportunity to develop human disease
      models in vitro, drug and toxicity screening tools, as well as a continuous
      autologous cell source for future cell-based therapies. Therefore, it is not
      surprising that the methods for generating iPSCs have significantly evolved over
      the past few years. To date the reprogramming methods include the use of various
      transfection/transduction systems, small molecules to enhance the reprogramming
      process, and to adapt to a multitude of different cell type sources. We are now
      able to convert essentially any somatic cell type into iPSCs with increased
      efficiency and at higher quality when compared to ESCs. More recently, this field
      has been expanded to direct reprogramming of one cell type to another, including
      lineage-specific progenitors. Here, we provide a concise review of methods to
      generate induced pluripotent stem cells, and discuss the most recent strategies
      augmenting the reprogramming process and increasing the quality of iPSCs.

PMID- 22959310
TI  - CT staging for breast cancer patients with poor prognostic tumours.
AB  - The aim of this study was to assess the value of computed tomography (CT) staging
      of the chest, abdomen and pelvis in patients with poor prognostic tumours and no
      symptoms of metastatic disease in those who have undergone primary surgical
      management for the treatment of breast cancer. Patients who had primary operable
      invasive breast cancer treated by surgery over a 2-year period were
      retrospectively identified. Pathological data from the surgical resection were
      used to calculate the Nottingham Prognostic Index. Patients with no symptoms of
      distant metastases who underwent CT staging of the chest, abdomen and pelvis as a
      result of being placed in the poor prognostic group were identified. The presence
      and sites of metastatic disease or any indeterminate finding were documented.
      Additional investigations generated as a result of the staging CT and the outcome
      were also recorded. Sixty-seven patients (80%) in the poor prognostic group
      underwent a staging CT. Forty-seven patients (70%) had no signs of metastatic
      disease on the staging CT. Two patients (3%) were diagnosed with metastatic
      disease, on the basis of the initial CT scan. Eighteen patients (27%) had an
      indeterminate finding requiring further investigation, generating 21 additional
      imaging tests - following this only one additional patient was diagnosed with
      metastatic disease. Seventeen patients with an initially indeterminate finding
      did not have metastatic disease, giving a false-positive rate of 25%. In total,
      three patients (4%) had a final diagnosis of metastatic disease. The routine use
      of CT staging in patients with no symptoms of distant metastases with primary
      operable breast cancer even when in a poor prognostic group is of limited value,
      with a low pick-up rate of metastatic disease and considerable risk of false
      positive findings.

PMID- 22959309
TI  - A prescription for 'stress'--the role of Hsp90 in genome stability and cellular
      adaptation.
AB  - Changes in cell homeostasis, or cell 'stress', are thought to tax the ability of
      the Hsp90 chaperone to facilitate an array of processes critical for genome
      maintenance. Here, we review the current understanding of how the Hsp90 chaperone
      machinery ensures the function of proteins important for DNA repair,
      recombination, and chromosome segregation. We discuss the idea that cell stress
      can overload Hsp90, resulting in genomic instability that may have important
      implications for stress adaptation and selection. The importance of Hsp90 in
      genome maintenance and its limited capacity to buffer the proteome may underlie
      the initiation or progression of diseases such as cancer.

PMID- 22959312
TI  - Hepatitis B and C virus infections as possible risk factor for pancreatic
      adenocarcinoma.
AB  - Pancreatic adenocarcinoma (PAC) is a very aggressive and lethal cancer, with a
      very poor prognosis, because of absence of early symptoms, advanced stage at
      presentation, early metastatic dissemination and lack of both specific tests to
      detect its growth in the initial phases and effective systemic therapies. To
      date, the causes of PAC still remain largely unknown, but multiple lines of
      evidence from epidemiological and laboratory researches suggest that about 15-20%
      of all cancers are linked in some way to chronic infection, in particular it has
      been shown that several viruses have a role in human carcinogenesis. The purpose
      of this report is to discuss the hypothesis that two well-known oncogenic
      viruses, Human B hepatitis (HBV) and Human C hepatitis (HCV) are a possible risk
      factor for this cancer. Therefore, with the aim to examine the potential link
      between these viruses and PAC, we performed a selection of observational studies
      evaluating this association and we hypothesized that some pathogenetic mechanisms
      involved in liver carcinogenesis might be in common with pancreatic cancer
      development in patients with serum markers of present or past HBV and HCV
      infections. To date the available observational studies performed are few,
      heterogeneous in design as well as in end-points and with not univocal results,
      nevertheless they might represent the starting-point for future larger and better
      designed clinical trials to define this hypothesized relationship. Should these
      further studies confirm an association between HBV/HCV infection and PAC,
      screening programs might be justified in patients with active or previous
      hepatitis B and C viral infection.

PMID- 22959311
TI  - Axillary lymphadenectomy for breast cancer. A randomized controlled trial
      comparing a bipolar vessel sealing system to the conventional technique.
AB  - AIM: To compare safety and efficacy of a bipolar vessel sealing system (BVSS) to
      the conventional technique in axillary node dissection. METHODS: 116 women with
      breast cancer were randomized to conventional node dissection surgical technique
      (control; n = 58) by scalpel and monopolar cautery or using an electrothermal
      BVSS (study group; n = 58). RESULTS: The median (range) total volume of fluid
      collected by drain and aspirations was 305 (30-1420) mL in the study group and
      335 (80-1070) mL in the control group (p = 0.325). The median (range) total
      volume of lymph collected by percutaneous aspirations was 207.5 (40-1050) mL in
      the study group and 505 (270-705) mL in the control group (p = 0.010). The
      incidence of seroma was similar in both groups (p = 0.845). The axillary drain
      was removed earlier in the study group than in controls (p = 0.046). CONCLUSION:
      The use of a BVSS offers marginal advantages when compared to the conventional
      technique.

PMID- 22959313
TI  - Zinc and multi-mineral supplementation should mitigate the pathogenic impact of
      cadmium exposure.
AB  - High-level cadmium (Cd) exposure has long been known to induce nephropathy,
      severe osteoporosis, and fractures in humans. More recent epidemiology, however,
      reveals that, in populations not known to have important industrial exposure to
      this heavy metal, high-normal blood or urine Cd levels correlate with increased
      risk for vascular disorders, cancers, diabetes, and total mortality, as well as
      osteoporosis and nephropathy. Since these disorders appear unlikely to expedite
      Cd absorption, and since Cd has promoted these pathologies in rodent studies, it
      seems reasonable to conclude that Cd is an important mediating risk factor for
      these disorders in humans. Avoiding tobacco smoke or frequent ingestion of
      shellfish or organ meats can lessen humans exposure to Cd, but the chief dietary
      sources of Cd are plant-derived foods - green leafy vegetables, whole grains,
      tubers, and root vegetables - typically recommended for their health-supportive
      properties; indeed, among non-smokers, vegans tend to have the highest Cd body
      burden. Fortunately, iron sufficiency and ample dietary intakes of calcium,
      magnesium, and zinc can impede absorption of dietary Cd, both by down-regulating
      intestinal expression of mineral transporters, and by directly competing with Cd
      for access to these transporters. Correction of iron deficiency appears to be of
      particular importance for controlling Cd absorption. Moreover, zinc
      supplementation can counteract the toxicity of Cd already in the body via
      induction of metallothionein, which binds Cd avidly via its sulfhydryl groups; so
      long as it remains sequestered in this form, Cd is innocuous. Zinc
      supplementation may in any case be recommendable, as optimal zinc status exerts
      protective anti-inflammatory, antioxidant, and immunosupportive effects. Inasmuch
      as the toxicity of Cd appears to be mediated in large part by oxidative stress,
      ingestion of spirulina, lipoic acid, melatonin, and N-acetylcysteine may also
      have potential for mitigating the risk associated with Cd exposure, as suggested
      by rodent studies. Hence, although Cd may prove to be a major risk factor for
      morbidity and mortality in humans, practical strategies for limiting its
      absorption and pathogenic impact are at hand.

PMID- 22959314
TI  - Tranexamic acid-bevacizumab synergy in HHT patients presenting pulmonary
      arteriovenous malformations.
AB  - Bevacizumab and tranexamic acid have shown efficacy in the treatment of epistaxis
      and liver involvement of HHT patients. We suggest therapeutic association of
      bevacizumab and tranexamic acid should be further evaluated for the prevention
      and treatment of early lung involvement in HHT.

PMID- 22959315
TI  - Growth, tolerance efficiency and phytoremediation potential of Ricinus communis
      (L.) and Brassica juncea (L.) in salinity and drought affected cadmium
      contaminated soil.
AB  - We have previously reported that Ricinus communis (castor) is more tolerant to
      soil cadmium (Cd) and more efficient for Cd phytoremediation than Brassica juncea
      (Indian mustard) (Bauddh and Singh, 2012). In the present study, R. communis was
      found more tolerant to salinity and drought in presence of Cd and removed more Cd
      in a given time than Indian mustard. R. communis produced 23 and twelve folds
      higher biomass in terms of fresh weight and dry weight, respectively than that in
      B. juncea during three months when grown in Cd contaminated soil in presence of
      100mM NaCl salinity and ten day water withdrawal based drought at 90 day after
      sowing (DAS). Castor plants showed stronger self-protection ability in form of
      proline bioaccumulation (r(2)=0.949) than Indian mustard (r(2)=0.932), whereas a
      lower r(2) for malondialdehyde (MDA) and total soluble protein in R. communis
      (r(2)=0.914 and r(2)=0.915, respectively) than that of B. juncea (r(2)=0.947 and
      r(2)=0.927, respectively) indicated a greater damage to cell membrane in Indian
      mustard during the multiple stress conditions. Though, the amount of Cd
      accumulated in the roots and shoots of Indian mustard was higher as per unit
      biomass than that in castor, total removal of the metal from soil was much higher
      in castor on per plant basis in the same period in presence of the stresses. R.
      communis accumulated about seventeen and 1.5 fold higher Cd in their roots and
      shoots, respectively than that of B. juncea in 90 DAS under the multiple
      stresses. Salinity alone enhanced Cd uptake, whereas drought stress reduced its
      uptake in both the plants.

PMID- 22959316
TI  - Uterine gland development begins postnatally and is accompanied by estrogen and
      progesterone receptor expression in the dog.
AB  - During neonatal and juvenile life, mammalian uteri undergo extensive structural
      and functional changes, including uterine gland differentiation and development.
      In sheep and mice, inhibition of neonatal uterine gland development induced by
      progestin treatment led to a permanent aglandular uterine phenotype and adult
      infertility, suggesting that this strategy might be useful for sterilizing dogs
      and other companion animals. The goal of this study was to define temporal
      patterns of adenogenesis (gland development), cell proliferation, and
      progesterone and estrogen receptor expression in uteri of neonatal and juvenile
      dogs as a first step toward determining whether neonatal progestin treatments
      might be a feasible contraceptive approach in this species. Uteri obtained from
      puppies at postnatal wk 1, 2, 4, 6, or 8 were evaluated histologically and
      immunostained for MKI67, a marker of cell proliferation, estrogen receptor-1, and
      progesterone receptor. Adenogenesis was under way at 1 wk of age, as indicated by
      the presence of nascent glands beginning to bud from the luminal epithelium, and
      rapid proliferation of both luminal epithelial and stromal cells. By Week 2,
      glands were clearly identifiable and proliferation of luminal, glandular, and
      stromal cells was pronounced. At Week 4, increased numbers of endometrial glands
      were evident penetrating uterine stroma, even as proliferative activity decreased
      in all cell compartments as compared with Week 2. Whereas gland development was
      most advanced at Weeks 6 to 8, luminal, glandular, and stromal proliferation was
      minimal, indicating that the uterus was nearly mitotically quiescent at this age.
      Both estrogen receptor-1 and progesterone receptor were expressed consistently in
      uterine stromal and epithelial cells at all ages examined. In summary, canine
      uterine adenogenesis was underway by 1 wk of age and prepubertal glandular
      proliferation was essentially complete by Week 6. These results provided
      information necessary to facilitate development of canine sterilization
      strategies based on neonatal progestin treatments designed to permanently inhibit
      uterine gland development and adult fertility.

PMID- 22959317
TI  - Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat
      prefrontal cortex.
AB  - The prefrontal cortex is the brain region sensitive to detrimental effects of
      stress and even mild stress can rapidly impair its function. Aside from
      initiating proadaptive neuroplastic changes in the prefrontal cortex, chronic
      stress may also increase vulnerability of cortical neurons to apoptosis.
      Understanding the mechanism of plasticity and apoptotic processes is of immense
      importance for therapy of stress-related psychiatric disorders. In this study we
      tested whether molecular alterations in the prefrontal cortex, which occurred
      upon chronic social isolation, could be influenced by a prolonged fluoxetine
      treatment. We analyzed the expression of synaptic plasticity and apoptotic
      molecular markers in the prefrontal cortex of young-adult male Wistar rats
      exposed to 6-week social isolation with and without fluoxetine treatment during
      the last 3 weeks. Compartmental redistribution of NFkappaB transcription factor,
      involved in regulation of plasticity and apoptosis, was also examined. The level
      of synaptosomal polysialic neural cell adhesion molecule (PSA-NCAM) was increased
      in the prefrontal cortex of isolated rats as compared to untreated controls.
      Treatment with fluoxetine reduced the PSA-NCAM level only in isolated animals. In
      addition, mitochondrial Bax protein was elevated by chronic social isolation,
      while fluoxetine failed to abolish this effect. In spite of elevated Bcl-2 in the
      mitochondria, the calculated Bax/Bcl-2 ratio and concomitant absence of NFkappaB
      activation pointed to initiation of apoptotic signaling in the prefrontal cortex.
      The results imply that fluoxetine influences plasticity in the prefrontal cortex
      of chronically isolated rats and fails to prevent stress-induced initiation of
      apoptosis in this brain structure.

PMID- 22959318
TI  - Intravenous dextrose for children with gastroenteritis and dehydration: a double
      blind randomized controlled trial.
AB  - STUDY OBJECTIVE: We seek to determine whether an initial intravenous bolus of 5%
      dextrose in normal saline solution compared with normal saline solution will lead
      to a lower proportion of hospitalized patients and a greater reduction in serum
      ketone levels in children with gastroenteritis and dehydration. METHODS: We
      enrolled children aged 6 months to 6 years in a double-blind, randomized
      controlled trial of patients presenting to a pediatric emergency department.
      Subjects were randomized to receive a 20 mL/kg infusion of either 5% dextrose in
      normal saline solution or normal saline solution. Serum ketone levels were
      measured before and at 1- and 2-hour intervals after the initial study fluid
      bolus administration. Primary outcome was the proportion of children
      hospitalized. Secondary outcome was change in serum ketone levels over time.
      RESULTS: One hundred eighty-eight children were enrolled. The proportion of
      children hospitalized did not differ between groups (35% in the 5% dextrose in
      normal saline solution group versus 44% in the normal saline solution group; risk
      difference 9%; 95% confidence interval [CI] -5% to 22%). Compared with children
      who received normal saline solution, those who received 5% dextrose in normal
      saline solution had a greater reduction in mean serum ketone levels at both 1
      hour (mean Delta 1.2 versus 0.1 mmol/L; mean difference 1.1 mmol/L; 95% CI 0.4 to
      1.9 mmol/L) and 2 hours (mean Delta 1.9 versus 0.3 mmol/L; mean difference 1.6
      mmol/L; 95% CI 0.9 to 2.3 mmol/L). CONCLUSION: Administration of a dextrose
      containing bolus compared with normal saline did not lead to a lower rate of
      hospitalization for children with gastroenteritis and dehydration. There was,
      however, a greater reduction in serum ketone levels in patients who received 5%
      dextrose in normal saline solution.

PMID- 22959319
TI  - Clinical outcome score predicts the need for neurodevelopmental intervention
      after infant heart surgery.
AB  - OBJECTIVE: Our goal was to determine if a clinical outcome score derived from
      early postoperative events is associated with 18- to 24-month Psychomotor
      Developmental Index (PDI) score among infants undergoing cardiopulmonary bypass
      surgery. METHODS: We included infants aged <=6 weeks who underwent surgery during
      2002-2006, all of whom were referred for neurodevelopmental evaluation at age 18
      to 24 months. We excluded children with chromosomal abnormalities, hearing loss,
      cerebral palsy, or a Bayley III assessment. The prespecified clinical outcome
      score had a range of 0 to 7. Lower scores indicated a more rapid postoperative
      recovery. Patients requiring extracorporeal membrane oxygenation were assigned a
      score of 7. RESULTS: Ninety-nine subjects were included. Surgical procedures were
      arterial switch (n = 36), Norwood (n = 26), repair of total anomalous pulmonary
      venous connection (n = 16), and other (n = 21). Four subjects had postoperative
      extracorporeal membrane oxygenation. Clinical outcome scores were highest in the
      Norwood group (mean 4.1 +/- 1.4) compared with the arterial switch group (1.9 +/-
      1.6) (P < .001), total anomalous pulmonary venous connection group (1.6 +/- 2.0)
      (P < .001), and other group (3.3 +/- 1.6, P = not significant). A mean decrease
      in PDI of 10.9 points (95% confidence interval, 4.9-16.9; P = .0005) was observed
      among children who had a clinical outcome score >=3, compared with those with a
      clinical outcome score <3. Time until lactate <=2.0 mmol/L increased with
      increasing clinical outcome score (P = .0003), as did highest 24-hour inotrope
      score (P < .0001). CONCLUSIONS: Clinical outcome scores of >=3 were associated
      with a significantly lower PDI at age 18 to 24 months. This score may be valuable
      as an end point when evaluating novel potential therapies for this high-risk
      population.

PMID- 22959320
TI  - Aortic root numeric model: correlation between intraoperative effective height
      and diastolic coaptation.

PMID- 22959321
TI  - Demonstration of persistent tumor cells 4 weeks after radiofrequency ablation of
      a pulmonary adenocarcinoma.

PMID- 22959322
TI  - Extracorporeal membrane oxygenation resuscitation in adult patients with
      refractory septic shock.
AB  - OBJECTIVES: Experience with extracorporeal membrane oxygenation for adult
      patients with refractory septic shock remains limited. We aimed to study the
      clinical features and outcomes of this patient group in an extracorporeal
      membrane oxygenation referral center in Taiwan. METHODS: From January 2005 to
      December 2010, all adult patients in refractory septic shock and requiring
      venoarterial extracorporeal membrane oxygenation for circulatory support were
      included in the present study. The variables analyzed included patient
      demographics; comorbidities; smoking status; hemodynamic, ventilatory, and
      laboratory parameters just before extracorporeal membrane oxygenation support;
      clinical course; extracorporeal membrane oxygenation details; complications;
      microbiology results; and outcomes. The primary endpoint was survival to hospital
      discharge. RESULTS: A total of 52 patients, 39 men and 13 women, were included
      during a 6-year period. Their median age and body mass index was 56.8 years and
      24.1 kg/m(2), respectively. Of the 52 patients, 39 (75%) had failure of at least
      3 organ systems and 21 (40%) had developed cardiac arrest and received
      cardiopulmonary resuscitation at extracorporeal membrane oxygenation
      implantation. Of these 52 patients, 8 (15%) survived to hospital discharge. The
      nonsurvivors were significantly older than the survivors (59.3 vs 43.8 years; P =
      .009), and all 20 patients (38%) aged 60 years or older died. CONCLUSIONS: In our
      single-center experience with extracorporeal membrane oxygenation for adults with
      refractory septic shock, the outcomes of these patients remain unsatisfactory.
      From our findings, we suggest that if extracorporeal membrane oxygenation were to
      be used in this patient population, age 60 years or older might be a
      contraindication. Also, central extracorporeal membrane oxygenation could
      possibly be beneficial according to the favorable pediatric experience in
      published studies.

PMID- 22959323
TI  - Effect of the prosthesis-patient mismatch on long-term clinical outcomes after
      isolated aortic valve replacement for aortic stenosis: a prospective
      observational study.
AB  - BACKGROUND: The effect of prosthesis-patient mismatch (PPM) on clinical outcomes
      after aortic valve replacement remains controversial. We evaluated effect of PPM
      on long-term clinical outcomes after isolated aortic valve replacement in
      patients with predominant aortic stenosis. METHODS: We analyzed data from
      patients with predominant aortic stenosis who underwent isolated aortic valve
      replacement between January 1995 and July 2010. The indexed effective orifice
      area, obtained by dividing the in vivo effective orifice area by the patient's
      body surface area, was used to define PPM as clinically nonsignificant (group I,
      224 patients), mild (group II, 52 patients), moderate (group III, 39 patients),
      and severe (group IV, 36 patients). RESULTS: Early survival was not significantly
      different among the groups, but overall survival was decreased gradually in group
      IV. Overall survival at 12 years was lower in group IV than in group I (92.8% +/-
      2.7% vs 67.0 +/- 10.1, respectively; P = .001). Cardiac-related-death-free
      survival at 12 years was lower in patients with severe PPM. Left ventricular mass
      index decreased during the follow-up period in all groups. But left ventricular
      mass index was less decreased in group IV compared with groups I, II, and III.
      Age, severe PPM, and ejection fraction <40%, and New York Heart Association
      Functional Class IV were independent risk factors of overall survival on
      multivariate analysis. Severe PPM was an independent risk factor for cardiac
      related death. CONCLUSIONS: Severe PPM showed an adverse effect on long-term
      survival, and was an independent risk factor for cardiac-related death. In
      addition, patients with severe PPM showed less decreasing left ventricular mass
      index during follow-up.

PMID- 22959324
TI  - Aortic root and valve surgery after arterial switch operation.

PMID- 22959325
TI  - Pulmonary hypertension is associated with worse early and late outcomes after
      aortic valve replacement: implications for transcatheter aortic valve
      replacement.
AB  - OBJECTIVES: Our objectives were to determine the prevalence of pulmonary
      hypertension (PHT) in patients undergoing aortic valve replacement (AVR) for
      severe aortic stenosis (AS), characterize risk for PHT, assess changes in PHT,
      and analyze its effect on outcomes. METHODS: From January 1996 to July 2010, a
      total of 4372 patients with severe AS underwent primary AVR. Right ventricular
      systolic pressure (RVSP), a surrogate for PHT, was estimated
      echocardiographically in 2385, the study group. Preoperative RVSP was less than
      35 mm Hg (low pressure) in 611, 35 to 50 mm Hg (moderate PHT) in 1199, and
      greater than 50 mm Hg (high PHT) in 575. From active follow-up, 10,218 patient
      years were available for survival analysis and 3716 echocardiograms after AVR for
      assessing RVSP. RESULTS: Median preoperative RVSP was 41 mm Hg (range, 10-104 mm
      Hg). Older, more symptomatic female patients with more comorbidities and
      tricuspid or mitral regurgitation had higher RVSP. Hospital mortality was higher
      in those with higher RVSP (0.9% low presssure, 1.9% moderate PHT, 3.1% high PHT,
      P = .03), as was risk of renal (P < .0001) or respiratory failure (P < .0001),
      sepsis (P = .01), and prolonged hospitalization (P < .0001). Initial post-AVR
      RVSP improvement was not maintained but rose to preoperative levels by 3 to 4
      years. Long-term survival was worse in patients with higher RVSP (P < .0001): 85%
      and 63% low pressure; 77% and 45% moderate PHT; and 62% and 31% high PHT at 5 and
      10 years, respectively. CONCLUSIONS: Most patients undergoing primary AVR have at
      least moderate PHT that is not relieved by AVR; its severity is associated with
      mortality, serious complications, and worse late survival. PHT severity should be
      included in risk assessment before aortic valve intervention. These outcomes
      suggest that earlier intervention for AS warrants further study.

PMID- 22959326
TI  - Tunneling of ventricular assist device outflow graft rostral to superior vena
      cava.

PMID- 22959327
TI  - On Cardiovascular Risk Estimation in Patients With Psoriasis: The REGICOR and
      SCORE Scales.

PMID- 22959328
TI  - A novel allelopathic substance, 13-epi-orthosiphol N, in Orthosiphon stamineus.
AB  - Orthosiphon stamineus (Java tea) has been widely used as traditional herb and
      several bioactive compounds against animal cells have been isolated. However, no
      bioactive compound against plants has been reported. Therefore, we investigated
      possible allelopathic properties and substances in O. stamineus. Aqueous methanol
      extracts of O. stamineus inhibited root and hypocotyl growth of cress (Lepidium
      sativum) and lettuce (Lactuca sativa) seedlings. Increasing the extract
      concentration increased the inhibition, which suggests that O. stamineus may have
      allelopathic properties. When the extract was divided into an ethyl acetate and
      an aqueous fraction, the ethyl acetate fraction showed the stronger inhibitory
      effect. Thus, the ethyl acetate phase was further purified, and the main
      allelopathic substance was isolated and identified as 13-epi-orthosiphol N, a
      novel compound, by spectral data. 13-epi-Orthosiphol N inhibited root and
      hypocotyl growth of cress and lettuce at concentrations greater than 10 MUmol/L.
      The concentrations required for 50% inhibition ranged from 41 to 102 MUmol/L.
      These results suggest that 13-epi-orthosiphol N may be an allelochemical and main
      contributor to the growth inhibitory effect of O. stamineus and may have
      potential as a template for the development of new plant control substances.

PMID- 22959329
TI  - Estimates of global mortality attributable to particulate air pollution using
      satellite imagery.
AB  - BACKGROUND: Epidemiological studies of the health effects of air pollution have
      traditionally relied upon ground-monitoring stations to measure ambient
      concentrations. Satellite derived air pollution measures offer the advantage of
      providing global coverage. OBJECTIVE: To undertake a global assessment of
      mortality associated with long-term exposure to fine particulate air pollution
      using remote sensing data. METHODS: Global PM(2.5) exposure levels were derived
      from the MODIS and MISR satellite instruments. Relative risks and attributable
      fractions of mortality were modeled using previously developed concentration
      response functions for the association between PM(2.5) and mortality. RESULTS:
      The global fraction of adult mortality attributable to the anthropogenic
      component of PM(2.5) (95% CI) was 8.0% (5.3-10.5) for cardiopulmonary disease,
      12.8% (5.9-18.5) for lung cancer, and 9.4% (6.6-11.8) for ischemic heart disease.
      CONCLUSION: This study demonstrates the feasibility of using satellite derived
      pollution concentrations in assessing the population health impacts of air
      pollution at the global scale. This approach leads to global estimates of
      mortality attributable to PM(2.5) that are greater than those based on fixed site
      ground-level measures of urban PM(2.5), but more similar to estimates based on
      global chemical transport model simulations of anthropogenic PM(2.5).

PMID- 22959331
TI  - [Imaging-guided percutaneous biopsy of tumors of the locomotor apparatus].
AB  - The prognosis of musculoskeletal sarcomas is related to appropriate management by
      specifically trained multidisciplinary teams. Musculoskeletal radiologists are
      responsible for the image-guided percutaneous biopsy of these tumors, which has a
      diagnostic accuracy of at least 80%. It is essential for radiologists to know: a)
      the limitations of percutaneous biopsy with respect to surgical biopsy; b) what
      should and should not be biopsied; c) how to appropriately plan percutaneous
      biopsy, with special attention to the route of approach, taking into account the
      compartmental anatomy and the route of approach after surgical treatment; and d)
      technical aspects of the procedure, like the area of the tumor to biopsy, the
      caliber of the needle, the number and length of the specimens to obtain to ensure
      optimal pathological diagnosis, and techniques in function of the imaging
      modality and bone penetration.

PMID- 22959330
TI  - [Positron emission tomography-computed tomography in tumors of the locomotor
      apparatus].
AB  - Positron emission tomography/computed tomography (PET/CT) is a hybrid imaging
      technique that combines the anatomic information from CT with the metabolic
      information acquired from PET after the administration of specific radiotracers,
      the most commonly used of which is F18-fluorodeoxyglucose (FDG). In oncology,
      this technique is based on the increased uptake of FDG by malignant lesions. In
      the locomotor apparatus, some uptake by bones and soft tissues is physiological
      or benign and this uptake must be differentiated from uptake by malignancies,
      whether primary or secondary. The most important limitations are active
      inflammatory or infectious processes, which are positive on PET images, and
      malignant lesions that are smaller than 1cm, cystic, necrotic, or low-grade,
      which are negative on PET images. PET/CT in the locomotor apparatus is especially
      useful for the detection of metastases from the most common tumors. It is also
      used for staging and monitoring the response to treatment of some hematological
      tumors like lymphoma, where it is fundamental to determine whether the bone
      marrow has been infiltrated, or myeloma. Lastly, although it is not yet an
      established indication, PET/CT is being increasingly used to study sarcomas,
      because it can provide additional information that can be useful for the
      characterization and grading of tumors, for guiding biopsies, for staging and re
      staging, and for evaluating the response to neoadjuvant therapy as well as for
      evaluating new drugs in clinical trials.

PMID- 22959332
TI  - Survey of quality, readability, and social reach of websites on osteosarcoma in
      adolescents.
AB  - OBJECTIVE: Little is known about Internet resources for adolescent patients. This
      study assessed the quality, readability, and social reach of websites on an
      illustrative adolescent cancer diagnosis, osteosarcoma. METHODS: The top 50
      results from four queries in two search engines were screened. Quality and
      readability were determined using standard DISCERN tool, Flesch Reading Ease and
      Flesch-Kinkaid Grade. Social reach was gauged by social networking links, global
      website traffic, and a pilot adolescent-specificity measure. RESULTS: Of 400
      websites assessed, 56 (14%) met inclusion criteria. Websites' mean quality was
      fair (49.8 on 75-point scale; range 31.0-66.0, poor to excellent); 86% failed
      readability standards (Grade>8); 75% offered at least one social networking link;
      and 34% offered site-specific social media. More than 60% received over 50,000
      visits in the past month. Only 12.5% included adolescent-specific content. Of the
      10 websites ranked highest for quality, only one achieved both readability
      targets and adolescent-specific content. CONCLUSIONS: Although some patient
      oriented websites on osteosarcoma are of acceptable quality, most failed
      readability targets, and few appeared to address adolescents. PRACTICE
      IMPLICATIONS: Better awareness of Internet health resources and social media for
      adolescents with cancer is needed to address gaps, promote health literacy and
      facilitate patient-provider communication.

PMID- 22959333
TI  - Differential effects of health knowledge and health empowerment over patients'
      self-management and health outcomes: a cross-sectional evaluation.
AB  - OBJECTIVE: The role of health knowledge and empowerment in explaining behavioral
      and health outcomes was treated in depth in the literature, but the combined
      effect of these constructs has been somehow neglected. This study presents an
      empirical, a priori, cross-sectional evaluation of the differential effects of
      health knowledge and empowerment on patients' self-management and health
      outcomes. METHODS: This study relies on a cross-sectional design involving a
      total of 209 Fibromyalgia patients. Structural Equation Modeling techniques were
      employed to analyze the model relationships. RESULTS: Knowledge and three
      empowerment dimensions were found to positively impact health outcomes. However,
      these relationships were not mediated by self-management. Self-management,
      operationalized in terms of physical exercise and drug intake, was found to be a
      strong predictor of health outcomes. CONCLUSION: Despite the lack of support for
      the mediating role of self-management, a strong impact of knowledge and
      empowerment over health outcomes was observed. Theories of health literacy and
      empowerment may benefit from this result by integrating both dimensions in an
      overall model of behavioral and health outcomes change. PRACTICE IMPLICATIONS:
      Results from this study suggest that health interventions targeted to chronic
      patients should focus simultaneously on knowledge and empowerment, rather than
      favoring one of these individual constructs.

PMID- 22959334
TI  - Intensity of conditioning for allogeneic haemopoetic cell transplantation.

PMID- 22959336
TI  - Efficacy and safety of sublingual immunotherapy in Asian children.
AB  - OBJECTIVE: Sublingual immunotherapy is currently accepted as a suitable
      alternative to subcutaneous immunotherapy because of its easy and painless
      administration and improved safety. Many clinical trials have demonstrated that
      sublingual immunotherapy is an effective and safe treatment for pollen or mite
      allergic rhinitis. However, there have been very few studies overall on children
      with allergic rhinitis who are sensitized to house-dust mites in Asia. The
      purpose of the present study was to investigate the efficacy and safety of
      sublingual immunotherapy in children with allergic rhinitis to house-dust mites.
      METHODS: A total of 112 patients under the age of 15 who had allergic rhinitis to
      Dermatophagoides pteronyssinus and Dermatophagoides farinae were included. All
      patients were treated with sublingual immunotherapy (Staloral((r))). Symptom
      scores and quality of life were evaluated by questionnaires until one year after
      sublingual immunotherapy. The medication score was assessed monthly using a diary
      medication card and serologic tests were evaluated before and 6 and 12 months
      after treatment. Adverse effects and compliance were also investigated. RESULTS:
      All nasal and non-nasal symptoms and quality of life were significantly improved
      after treatment. The total medication score was decreased significantly after
      sublingual immunotherapy. There was no significant change in serologic tests.
      Some minor adverse effects were reported, however there were no systemic
      reactions. The drop-out rate was 21%. CONCLUSIONS: Sublingual immunotherapy is a
      valuable therapy for the treatment of allergic rhinitis in Asian children
      sensitized to house-dust mites.

PMID- 22959335
TI  - Reduced-intensity conditioning versus standard conditioning before allogeneic
      haemopoietic cell transplantation in patients with acute myeloid leukaemia in
      first complete remission: a prospective, open-label randomised phase 3 trial.
AB  - BACKGROUND: Reduced-intensity conditioning regimens have been developed to
      minimise early toxic effects and deaths after allogeneic haemopoietic cell
      transplantation. However, the efficacy of these regimens before this procedure
      has not been investigated in a randomised trial. In this prospective, open-label
      randomised phase 3 trial we compared a reduced-intensity fludarabine-based
      conditioning regimen with a standard regimen in patients with acute myeloid
      leukaemia in first complete remission. METHODS: Patients were aged 18-60 years
      and had intermediate-risk or high-risk acute myeloid leukaemia (defined by
      cytogenetics) in first complete remission; an available HLA-matched sibling donor
      or an unrelated donor with at least nine of ten HLA alleles; and adequate renal,
      cardiac, pulmonary, and neurological function. Between Nov 15, 2004, and Dec 31,
      2009, patients were randomly assigned (1:1, by a computer-based minimisation
      procedure that balanced patients for age, cytogenetic risk, induction therapy,
      and donor type) to receive either reduced-intensity conditioning of four doses of
      2 Gy of total-body irradiation and 150 mg/m(2) fludarabine or standard
      conditioning of six doses of 2 Gy of total-body irradiation and 120 mg/kg
      cyclophosphamide. All patients were given ciclosporin and methotrexate as
      prophylaxis against graft-versus-host disease. Neither investigators nor patients
      were blinded to study treatment. Our primary endpoint was the incidence of non
      relapse mortality, analysed in the intention-to-treat population. The trial is
      registered with ClinicalTrials.gov, number NCT00150878. FINDINGS: The trial was
      stopped early on Dec 31, 2009, because of slow accrual of patients. 99 patients
      were randomly assigned to receive reduced-intensity conditioning and 96 to
      receive standard conditioning. The incidence of non-relapse mortality did not
      differ between the reduced-intensity and standard conditioning groups (cumulative
      incidence at 3 years 13% [95% CI 6-21] vs 18% [10-26]; HR 0.62 [95% CI 0.30
      1.31]). Relapse incidence (cumulative incidence 3 years 28% [95% CI 19-38] vs 26%
      [17-36]; HR 1.10 [95% CI 0.63-1.90]), disease-free survival (3 year disease-free
      survival 58% [95% CI 49-70] vs 56% [46-67]; HR 0.85 [95% CI 0.55-1.32]), and
      overall survival (3 year overall survival 61% [95% CI 50-74] vs 58% [47-70]; HR
      0.77 [95% CI 0.48-1.25]) did not differ significantly between groups. Grade 3-4
      of oral mucositis was less common in the reduced-intensity group than in the
      standard conditioning group (50 patients in the reduced-intensity conditioning
      group vs 73 patients in the standard conditioning group); the frequency of other
      side-effects such as graft-versus-host disease and increased concentrations of
      bilirubin and creatinine did not differ significantly between groups.
      INTERPRETATION: Reduced-intensity conditioning results in a similar incidence of
      non-relapse mortality and reduced toxic effects compared with standard
      conditioning without affecting survival outcomes, and thus could be
      preferentially used in patients younger than 60 years with acute myeloid
      leukaemia transplanted in first complete remission.

PMID- 22959337
TI  - [Achalasia: role of endoscopic therapy and surgery].
AB  - Pneumatic dilation of achalasia has a same medium-term efficacy than surgery and
      is commonly proposed as the first-line treatment. Intra-sphincteric injection of
      botulinum toxin is reserved for elderly patients with serious comorbidities. Per
      endoscopic myotomy is possible but needs to be evaluated by further studies.
      Laparoscopic Heller's myotomy in first intension is reserved for young patients
      less than 40 years. Results of Heller's myotomy are not modified by prior
      endoscopic treatment or by mega-esophagus. Better surgery results are shown in
      recent and severe achalasia.

PMID- 22959338
TI  - [Early repolarisation with ventricular fibrillation in a young woman].

PMID- 22959339
TI  - [Do antidepressant treatments influence self-harm and aggressive behaviors?].
AB  - Depression is a frequent disorder with a lifetime prevalence of 25% in women and
      12% in men. General practitioners are responsible for the majority of
      antidepressant prescriptions in France. Antidepressant treatments decrease the
      suicide risk in adult patients with a depressive disorder or suicidal behavior.
      However, antidepressant treatment is not recommended in children or adolescents.
      Indeed, an increase risk of suicide has been reported in this population in
      previous studies, especially when antidepressant treatment is started. The
      treatment of adolescents with major depression or suicidal behaviors must be
      preferentially conducted by a specialized care team. A clinical evaluation must
      be done very carefully before the onset of antidepressant treatment. In some
      specific clinical contexts, antidepressant treatments may be used to decrease
      levels of impulsiveness and aggressiveness. However, the efficacy of
      antidepressant treatment on violent behaviors is still not clearly determined by
      scientific literature owing to lack of studies with a high level of evidence. In
      a few cases of patients, activation syndromes may appear at the beginning of
      antidepressant treatments, with akathisia, nervousness, anxiety, insomnia and
      agitation. These reactions may be risk factors for acting out. Alcohol, cocaine
      or benzodiazepines when concomitantly consumed with antidepressant treatment may
      increase the risk for acting out. Whenever benzodiazepines are needed in a
      patient with a high suicide risk, the dosage used must be enough to avoid
      desinhibition and to obtain anxiolytic and sedative effects.

PMID- 22959340
TI  - Prevalence of night eating in obese individuals with schizophrenia and
      schizoaffective disorder.
AB  - The prevalence of Night Eating Syndrome (NES) in the general population is
      estimated to be 1.5%, however, the rates among individuals with schizophrenia and
      schizoaffective disorder are not yet established. This study sought to examine
      the frequency and correlates of NES-related behaviors in a sample of obese
      patients with schizophrenia. One-hundred outpatients diagnosed with schizophrenia
      or schizoaffective disorders completed the self-report Night Eating Questionnaire
      (NEQ) and were then interviewed as a follow-up for the specific assessment of
      NES. Based on a diagnostic interview, 12% of this sample met full criteria for
      NES, with an additional 10% meeting partial criteria for NES. Based on the NEQ
      alone, 8% met full criteria with an additional 8% meeting partial criteria. Night
      eating behaviors were associated with increased insomnia and depression. Our
      findings suggest that screening for NES among patients with serious mental
      illness may efficiently identify a subgroup with additional clinical needs.

PMID- 22959341
TI  - The impact of National Death Index linkages on population-based cancer survival
      rates in the United States.
AB  - BACKGROUND: In order to ensure accurate survival estimates, population-based
      cancer registries must ascertain all, or nearly all, patients diagnosed with
      cancer in their catchment area, and obtain complete follow-up information on all
      deaths that occurred among registered cancer patients. In the US, linkage with
      state death records may not be sufficient to ascertain all deaths. Since 1979,
      all state vital statistics offices have reported their death certificate
      information to the National Death Index (NDI). OBJECTIVE: This study was designed
      to measure the impact of linkage with the NDI on population-based relative and
      cancer cause-specific survival rates in the US. METHODS: Central cancer registry
      records for patients diagnosed 1993-1995 from California, Colorado, and Idaho
      were linked with death certificate information (deaths 1993-2004) from their
      individual state vital statistics offices and with the NDI. Two databases were
      created: one contained incident records with deceased patients linked only to
      state death records and the second database contained incident records with
      deceased patients linked to both state death records and the NDI. Survival
      estimates and 95% confidence intervals from each database were compared by state
      and primary site category. RESULTS: At 60 months follow-up, 42.1-48.1% of
      incident records linked with state death records and an additional 0.7-3.4% of
      records linked with the NDI. Survival point estimates from the analysis without
      NDI were not contained within the corresponding 95% CIs from the NDI augmented
      analysis for all sites combined and colorectal, pancreas, lung and bronchus,
      breast, prostate, non-Hodgkin lymphoma, and Kaposi sarcoma cases in all 3 states
      using relative survival methods. Additional combinations of state and primary
      site had significant survival estimate differences, which differed by method
      (relative versus cause-specific survival). CONCLUSION: To ensure accurate
      population-based cancer survival rates, linkage with the National Death Index to
      ascertain out of state and late registered deaths is a necessary process for US
      central cancer registries.

PMID- 22959342
TI  - TRIM28, a new molecular marker predicting metastasis and survival in early-stage
      non-small cell lung cancer.
AB  - TRIM28 is a universal corepressor for Kruppel-associated box zinc finger
      proteins. In this study, we demonstrated the expression of TRIM28 gene was
      significantly higher in cancerous tissues than in noncancerous tissues (P <
      0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid
      media as well as in soft agar. The proliferation rate was impaired and the cell
      cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung
      cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction
      to detect circulating cancer cells in 138 non-small cell lung cancer patients.
      The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of
      NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month
      follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had
      recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28
      negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer
      patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor
      specific survival compared with those with absent TRIM28 expression (P < 0.001).
      Results of our study showed that TRIM28 provides a survival advantage to lung
      cancer cells and may be a new marker to predict metastasis and prognosis in early
      stage non-small cell lung cancer patients.

PMID- 22959343
TI  - Association between seated postural control and gait speed in knee
      osteoarthritis.
AB  - The purpose of this study was to evaluate, in patients with knee osteoarthritis,
      whether seated postural control is a multivariate predictor of gait speed, after
      adjusting for the effects of conventional knee impairments. Sixty-seven patients
      with knee osteoarthritis awaiting total knee replacement participated. To measure
      seated postural control, patients sat on a balance board, and the centre-of
      pressure (COP) measures calculated in the anterior-posterior (AP) and medio
      lateral (ML) directions were standard deviation (SD) and mean frequency (MF).
      Isometric knee extensor strength was measured using an isokinetic dynamometer;
      knee flexion range-of-motion, an extendable goniometer; and knee pain intensity,
      a numeric pain rating scale. Fast-pace gait speed was assessed by the 10-m walk
      test and a poor gait speed was defined at a cutoff value of 1.0m/s. At the
      univariate level, the seated COP measures, with the exception of AP-MF,
      discriminated between patients with and without poor gait speed; however, only ML
      MF retained its predictive value in multivariable analyses adjusted for
      demographic, anthropometric, and knee impairment measures. These findings suggest
      that seated postural control may be an important correlate of physical function
      in patients with knee OA and that greater emphasis in the assessment of trunk
      control may be warranted in this population.

PMID- 22959344
TI  - Mitochondrial oxygen consumption in permeabilized fibers and its link to colour
      changes in bovine M. semimembranosus muscle.
AB  - Animal and muscle characteristics were recorded for 41 cattle. The oxygen
      consumption rate (OCR) of M. semimembranosus was measured between 3.0-6.4h post
      mortem (PM3-6) and after 3 weeks in a vacuum pack at 4 degrees C. Colour change
      measurements were performed following the 3 weeks using reflectance spectra (400
      1,100 nm) and the colour coordinates L, a and b, with the samples being packaged
      in oxygen permeable film and stored at 4 degrees C for 167 h. Significant
      individual animal differences in OCR at PM3-6 were found for mitochondrial
      complexes I and II. OCR of complex I declined with increased temperature and time
      PM, while residual oxygen-consuming side-reactions (ROX) did not. OCR of stored
      muscles was dominated by complex II respiration. A three-way regression between
      samples, colour variables collected upon air exposure and OCR of 3 weeks old
      fibres revealed a positive relationship between OCR and complex II activity and
      also between OCR and OCR(ROX). The presence of complex I and beta-oxidation
      activities increased metmyoglobin formation.

PMID- 22959345
TI  - DAD2 is an alpha/beta hydrolase likely to be involved in the perception of the
      plant branching hormone, strigolactone.
AB  - Strigolactones are a recently discovered class of plant hormone involved in
      branching, leaf senescence, root development, and plant-microbe interactions.
      They are carotenoid-derived lactones, synthesized in the roots and transported
      acropetally to modulate axillary bud outgrowth (i.e., branching). However, a
      receptor for strigolactones has not been identified. We have identified the DAD2
      gene from petunia, an ortholog of the rice and Arabidopsis D14 genes, and present
      evidence for its roles in strigolactone perception and signaling. DAD2 acts in
      the strigolactone pathway, and the dad2 mutant is insensitive to the
      strigolactone analog GR24. The crystal structure of DAD2 reveals an alpha/beta
      hydrolase fold containing a canonical catalytic triad with a large internal
      cavity capable of accommodating strigolactones. In the presence of GR24 DAD2
      interacts with PhMAX2A, a central component of strigolactone signaling, in a GR24
      concentration-dependent manner. DAD2 can hydrolyze GR24, with mutants of the
      catalytic triad abolishing both this activity and the ability of DAD2 to interact
      with PhMAX2A. The hydrolysis products can neither stimulate the protein-protein
      interaction nor modulate branching. These observations suggest that DAD2 acts to
      bind the mobile strigolactone signal and then interacts with PhMAX2A during
      catalysis to initiate an SCF-mediated signal transduction pathway.

PMID- 22959346
TI  - Sensitivity to temporal reward structure in amygdala neurons.
AB  - The time of reward and the temporal structure of reward occurrence fundamentally
      influence behavioral reinforcement and decision processes [1-11]. However,
      despite knowledge about timing in sensory and motor systems [12-17], we know
      little about temporal mechanisms of neuronal reward processing. In this
      experiment, visual stimuli predicted different instantaneous probabilities of
      reward occurrence that resulted in specific temporal reward structures. Licking
      behavior demonstrated that the animals had developed expectations for the time of
      reward that reflected the instantaneous reward probabilities. Neurons in the
      amygdala, a major component of the brain's reward system [18-29], showed two
      types of reward signal, both of which were sensitive to the expected time of
      reward. First, the time courses of anticipatory activity preceding reward
      delivery followed the specific instantaneous reward probabilities and thus
      paralleled the temporal reward structures. Second, the magnitudes of responses
      following reward delivery covaried with the instantaneous reward probabilities,
      reflecting the influence of temporal reward structures at the moment of reward
      delivery. In being sensitive to temporal reward structure, the reward signals of
      amygdala neurons reflected the temporally specific expectations of reward. The
      data demonstrate an active involvement of amygdala neurons in timing processes
      that are crucial for reward function.

PMID- 22959347
TI  - The perception and misperception of specular surface reflectance.
AB  - The amount and spectral content of the light reflected by most natural surfaces
      depends on the structure of the light field, the observer's viewing position, and
      3D surface geometry, particularly for specular (glossy) surfaces. A growing body
      of data has demonstrated that perceived surface gloss can vary as a function of
      its 3D shape and its illumination field, but there is currently no explanation
      for these effects. Here, we show that the perception of gloss can be understood
      as a direct consequence of image properties that covary with surface geometry and
      the illumination field. We show that different illumination fields can generate
      qualitatively different patterns of interaction between perceived gloss and 3D
      surface geometry. Despite the complexity and variability of these interactions,
      we demonstrate that the perception (and misperception) of gloss is well predicted
      by the way that each illumination field modulates the size, contrast, sharpness,
      and depth of specular reflections. Our results provide a coherent explanation of
      the effects of extrinsic scene variables on perceived gloss, and our methods
      suggest a general technique for assessing the role of specific image properties
      in modulating our visual experience of material properties.

PMID- 22959348
TI  - Competition, not cooperation, dominates interactions among culturable microbial
      species.
AB  - Microbial cells secrete numerous enzymes, scavenging molecules, and signals that
      can promote the growth and survival of other cells around them [1-4]. This
      observation is consistent with the evolution of cooperation within species [5],
      and there is now an increasing emphasis on the importance of cooperation between
      different microbial species [4, 6]. We lack, however, a systematic test of the
      importance of mutually positive interactions between different species, which is
      vital for assessing the commonness and importance of cooperative evolution in
      natural communities. Here, we study the extent of mutually positive interaction
      among bacterial strains isolated from a common aquatic environment. Using data
      collected from two independent experiments evaluating community productivity
      across diversity gradients, we show that (1) in pairwise species combinations,
      the great majority of interactions are net negative and (2) there is no evidence
      that strong higher-order positive effects arise when more than two species are
      mixed together. Our data do not exclude the possibility of positive effects in
      one direction where one species gains at the expense of another, i.e., predator
      prey-like interactions. However, these do not constitute cooperation and our
      analysis suggests that the typical result of adaptation to other microbial
      species will be competitive, rather than cooperative, phenotypes.

PMID- 22959349
TI  - Telomere-nuclear envelope dissociation promoted by Rap1 phosphorylation ensures
      faithful chromosome segregation.
AB  - Efficient chromosomal movements are important for the fidelity of chromosome
      segregation during mitosis; however, movements are constrained during interphase
      by tethering of multiple domains to the nuclear envelope (NE). Higher eukaryotes
      undergo open mitosis accompanied by NE breakdown, enabling chromosomes to be
      released from the NE, whereas lower eukaryotes undergo closed mitosis, in which
      NE breakdown does not occur. Although the chromosomal movements in closed mitosis
      are thought to be restricted compared to open mitosis, the cells overcome this
      problem by an unknown mechanism that enables accurate chromosome segregation.
      Here, we report the spatiotemporal regulation of telomeres in Schizosaccharomyces
      pombe closed mitosis. We found that the telomeres, tethered to the NE during
      interphase, are transiently dissociated from the NE during mitosis. This
      dissociation from the NE is essential for accurate chromosome segregation because
      forced telomere tethering to the NE causes frequent chromosome loss. The
      phosphorylation of the telomere protein Rap1 during mitosis, primarily by Cdc2,
      impedes the interaction between Rap1 and Bqt4, a nuclear membrane protein,
      thereby inducing telomere dissociation from the NE. We propose that the telomere
      dissociation from the NE promoted by Rap1 phosphorylation is critical for the
      fidelity of chromosome segregation in closed mitosis.

PMID- 22959351
TI  - Locally recurrent prostate cancer following radiation therapy: to cut or to
      freeze?

PMID- 22959350
TI  - Integration of a retrograde signal during synapse formation by glia-secreted TGF
      beta ligand.
AB  - Glial cells are crucial regulators of synapse formation, elimination, and
      plasticity [1, 2]. In vitro studies have begun to identify glial-derived
      synaptogenic factors [1], but neuron-glia signaling events during synapse
      formation in vivo remain poorly defined. The coordinated development of pre- and
      postsynaptic compartments at the Drosophila neuromuscular junction (NMJ) depends
      on a muscle-secreted retrograde signal, the TGF-beta/BMP Glass bottom boat (Gbb)
      [3, 4]. Muscle-derived Gbb activates the TGF-beta receptors Wishful thinking
      (Wit) and either Saxophone (Sax) or Thick veins (Tkv) in motor neurons [3, 4].
      This induces phosphorylation of Mad (P-Mad) in motor neurons, its translocation
      into the nucleus with a co-Smad, and activation of transcriptional programs
      controlling presynaptic bouton growth [5]. Here we show that NMJ glia release the
      TGF-beta ligand Maverick (Mav), which likely activates the muscle activin-type
      receptor Punt to potently modulate Gbb-dependent retrograde signaling and
      synaptic growth. Loss of glial Mav results in strikingly reduced P-Mad at NMJs,
      decreased Gbb transcription in muscle, and in turn reduced muscle-to-motor neuron
      retrograde TGF-beta/BMP signaling. We propose that by controlling Gbb release
      from muscle, glial cells fine tune the ability of motor neurons to extend new
      synaptic boutons in correlation to muscle growth. Our work identifies a novel
      glia-derived synaptogenic factor by which glia modulate synapse formation in
      vivo.

PMID- 22959352
TI  - Hospitalization costs for radical prostatectomy attributable to robotic surgery.
AB  - BACKGROUND: With health technology innovation responsible for higher health care
      costs, it is essential to have accurate estimates regarding the differential
      costs between robot-assisted radical prostatectomy (RARP) and open radical
      prostatectomy (ORP). OBJECTIVE: To describe the total hospitalization costs
      attributable to robotic and open surgery for radical prostatectomy (RP). DESIGN,
      SETTING, AND PARTICIPANTS: Using a population-based cohort by merging the
      Nationwide Inpatient Sample (NIS) and the American Hospital Association (AHA)
      survey from 2006 to 2008, we identified 29 837 prostate cancer patients who
      underwent RP. INTERVENTIONS: ORP and RARP. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The primary outcome was total hospitalization costs adjusted to year
      2008 US dollars. Generalized estimating equations were used to identify patient
      and hospital characteristics associated with total hospitalization costs and to
      estimate costs of ORP and RARP adjusted for case mix and hospital teaching
      status, location, and annual case volume. RESULTS AND LIMITATIONS: Overall, 20
      424 (68.5%) patients were surgically treated with RARP, and 9413 (31.5%) patients
      underwent ORP. Compared to ORP, patients undergoing RARP had shorter median
      length of stay (1 d vs 2 d; p<0.001) and were less likely to experience any
      postoperative complications (8.2% vs 11.3%; p<0.001). However, patients
      undergoing RARP had higher median hospitalization costs ($10409 vs $8862;
      p<0.001). After adjusting for patient and hospital features, RARP was associated
      with higher total hospitalization costs compared to ORP ($11932 vs $9390;
      p<0.001). Our results are limited by a study design using retrospective
      population-based data. CONCLUSIONS: Despite RARP having lower complications and
      shorter length of stay than ORP, total hospitalization costs are higher for
      patients treated with RARP compared with those treated with ORP.

PMID- 22959353
TI  - It's time to change the treatment paradigm for prostate cancer!

PMID- 22959354
TI  - The ubiquity of model-based reinforcement learning.
AB  - The reward prediction error (RPE) theory of dopamine (DA) function has enjoyed
      great success in the neuroscience of learning and decision-making. This theory is
      derived from model-free reinforcement learning (RL), in which choices are made
      simply on the basis of previously realized rewards. Recently, attention has
      turned to correlates of more flexible, albeit computationally complex, model
      based methods in the brain. These methods are distinguished from model-free
      learning by their evaluation of candidate actions using expected future outcomes
      according to a world model. Puzzlingly, signatures from these computations seem
      to be pervasive in the very same regions previously thought to support model-free
      learning. Here, we review recent behavioral and neural evidence about these two
      systems, in attempt to reconcile their enigmatic cohabitation in the brain.

PMID- 22959355
TI  - Efficacy of inducible protein 10 as a biomarker for the diagnosis of
      tuberculosis.
AB  - OBJECTIVE: This study evaluated inducible protein 10 (IP-10) as a diagnostic
      biomarker for specific tuberculosis (TB) infection and evaluated the ability of
      IP-10 to distinguish between active TB and latent TB infection (LTBI). METHODS:
      Forty-six patients with active pulmonary TB, 22 participants with LTBI, and 32
      non-TB controls were enrolled separately. We measured IP-10 in serum and in
      supernatants from whole blood stimulated with TB-specific antigens. RESULTS: TB
      antigen-dependent IP-10 secretion was significantly increased in the active TB
      patients and LTBI subjects compared with controls, but did not differ
      significantly between the active TB patients and LTBI subjects. Serum IP-10
      levels were higher in active TB than in LTBI (174.9 vs. 102.7pg/ml, p=0.002). The
      respective rates of positive responders of TB antigen-dependent IP-10 were 97.8%,
      90.9%, and 12.5% in active TB, LTBI, and non-TB controls, respectively. For serum
      IP-10, 87.5%, 45.5%, and 9.5% of responders were positive in the respective
      groups. CONCLUSIONS: The IP-10 response to TB antigen may constitute a specific
      biomarker for TB infection, but does not by itself distinguish between active TB
      and LTBI. Serum IP-10 may enhance the diagnostic performance when used in
      combination with another marker.

PMID- 22959356
TI  - Hydroxylated biphenyl derivatives are positive modulators of human GABA(A)
      receptors.
AB  - A series of 7 hydroxylated biphenyl derivatives (1-7) were prepared to evaluate
      their ability to modulate the function of several ligand gated ion channel (LGIC)
      recombinant receptors expressed in Xenopus laevis oocytes. Compounds 1, 3, 4, 6
      and 7 are natural occurring compounds whereas the synthesis of compounds 2 and 5
      was previously reported (Delogu et al., 2004; Fabbri et al., 2007). None of the
      compounds tested were able to modify, the activity of the strychnine-sensitive
      glycine receptor, or the activity of nicotinic receptor. The function of the
      5HT(3A) receptor was partially inhibited by all compounds tested, however this
      inhibition occurred at relatively high concentrations (100 MUM). All compounds,
      with the exception of compound 6, potentiate the action of gamma-aminobutyric
      acid (GABA)-evoked Cl(-) currents in Xenopus laevis oocytes expressing
      recombinant human alpha(1)beta(2)gamma(2L) GABA(A) receptors. Compounds 1, 2, 5
      and 7 enhance the function of the GABA(A) receptor at concentrations higher than
      3-10 MUM. Compound 4 was the most efficacious. However, compound 3 was the most
      potent (EC(50) 0.8 MUM). The potency of compound 3 in modulating the function of
      the GABA(A) receptor was comparable to that of diazepam, propofol or
      allopregnanolone. The enhancement of the GABA evoked Cl(-) currents by compound 3
      was not affected by flumazenil. Compound 3 did not induce loss of the righting
      reflex in rats suggesting that it is not an anesthetic agent, however, its
      ability in protecting the animals from seizures induced by picrotoxin confirm
      that its action occurs through the GABA(A) receptor.

PMID- 22959357
TI  - Ribavirin-induced externalization of phosphatidylserine in erythrocytes is
      predominantly caused by inhibition of aminophospholipid translocase activity.
AB  - Ribavirin in combination with interferon-alpha is the standard treatment for
      chronic hepatitis C, but often induces severe anemia forcing discontinuation of
      the therapy. Whereas suppression of bone marrow by interferon may impact on the
      production of erythrocytes, it has been suggested that accumulation of ribavirin
      in erythrocytes induces alterations causing an early removal of these cells by
      the mononuclear phagocytic system. Externalization of phosphatidylserine, which
      is exclusively present in the cytoplasmic leaflet of the plasma membrane, is a
      recognition signal for phagocytosis in particular of apoptotic cells. Here, we
      demonstrate that surface exposure of phosphatidylserine upon prolonged treatment
      of erythrocytes with ribavirin results mainly from inactivation of the
      aminophospholipid translocase, an ATP-dependent lipid pump, which specifically
      transports phosphatidylserine from the outer to the inner leaflet of the plasma
      membrane. Inactivation is due to severe ATP depletion, although competitive
      inhibition by ribavirin or its phosphorylated derivatives cannot be excluded.
      Phospholipid scramblase, responsible for collapse of lipid asymmetry, appears to
      be of minor importance as erythrocytes of patients with the Scott syndrome,
      lacking Ca(2+)-induced lipid scrambling, are equally sensitive to ribavirin
      treatment. Neither the antioxidant N-acetylcysteine nor the pan-caspase inhibitor
      Q-VD-OPH did affect ribavirin-induced phosphatidylserine exposure, suggesting
      that oxidative stress or apoptotic-related mechanisms are not involved in this
      process. In conclusion, we propose that spontaneous loss of lipid asymmetry, not
      corrected by aminophospholipid translocase activity, is the mechanism for
      ribavirin-induced phosphatidylserine exposure that may contribute to ribavirin
      induced anemia.

PMID- 22959358
TI  - Parents as a resource: communication quality affects the relationship between
      adolescents' internet use and loneliness.
AB  - The authors examined the influence of parent-adolescent communication quality, as
      perceived by the adolescents, on the link between adolescents' Internet use and
      loneliness, controlling for perceived family support in general terms.
      Adolescents (N = 216, M(age) = 15.80 years) provided data on Internet use,
      loneliness, Internet-related parent-adolescent communication, and perceived
      family support. Moderated regression analyses showed that Internet-related
      communication quality determined whether more extensive Internet use was
      associated with more loneliness. This moderation effect remained significant when
      perceived family support in general terms was controlled for. Gender and age of
      the participants did not influence the findings. Implications for successful
      Internet-related parenting strategies are discussed.

PMID- 22959360
TI  - Building a basis for action: enhancing public health surveillance of vision
      impairment and eye health in the United States.
AB  - PURPOSE: To examine the ability of current surveillance systems to assess and
      monitor disparities in: (1) vision impairment, (2) eye disease, (3) vision
      related functioning, (4) access to vision and eye care, and (5) access to
      supports and services for those needing vision rehabilitation. DESIGN: Review of
      surveillance systems and instruments. METHODS: We defined surveys and
      surveillance systems as data collection systems that used an active survey or
      data abstraction instrument, regardless of the sampling unit, and excluded
      strictly administrative data sources. We assessed 8 surveys against key
      surveillance attributes of representativeness, flexibility, and timeliness, as
      well as their contribution to establishing a national vision surveillance system.
      RESULTS: The key challenges facing a national vision surveillance system are: (1)
      the lack of consistent outcome data with adequate sample size and coverage to
      enable identification and tracking of vision health disparities, (2) lack of
      standardized data elements, and (3) a paucity of data that influence disability
      such as behavioral and environmental data. CONCLUSIONS: Current systems for
      assessing and monitoring vision health in the United States are limited and do
      not provide adequate information to guide interventions and policy decisions.
      Vision surveillance can help to document the burden of the condition, to identify
      high-risk populations, to develop strategies to reduce the individual and
      societal burden, and to guide public health programs and policies. Existing
      surveillance systems could be enhanced by integrating data and by periodically
      including patient-reported outcomes measurements including, but not limited to,
      specific barriers for people with vision impairment and related disabilities.

PMID- 22959359
TI  - Assessing retinal structure in complete congenital stationary night blindness and
      Oguchi disease.
AB  - PURPOSE: To examine retinal structure and changes in photoreceptor intensity
      after dark adaptation in patients with complete congenital stationary night
      blindness and Oguchi disease. DESIGN: Prospective, observational case series.
      METHODS: We recruited 3 patients with complete congenital stationary night
      blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by
      mutations in GRK1, and 1 normal control. Retinal thickness was measured from
      optical coherence tomography images. Integrity of the rod and cone mosaic was
      assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the
      patients after a period of dark adaptation and examined layer reflectivity on
      optical coherence tomography in a patient with Oguchi disease under light- and
      dark-adapted conditions. RESULTS: Retinal thickness was reduced in the parafoveal
      region in patients with GRM6 mutations as a result of decreased thickness of the
      inner retinal layers. All patients had normal photoreceptor density at all
      locations analyzed. On removal from dark adaptation, the intensity of the rods
      (but not cones) in the patients with Oguchi disease gradually and significantly
      increased. In 1 Oguchi disease patient, the outer segment layer contrast on
      optical coherence tomography was 4-fold higher under dark-adapted versus light
      adapted conditions. CONCLUSIONS: The selective thinning of the inner retinal
      layers in patients with GRM6 mutations suggests either reduced bipolar or
      ganglion cell numbers or altered synaptic structure in the inner retina. Our
      finding that rods, but not cones, change intensity after dark adaptation suggests
      that fundus changes in Oguchi disease are the result of changes within the rods
      as opposed to changes at a different retinal locus.

PMID- 22959361
TI  - Comparison of the progression rates of the superior, inferior, and both hemifield
      defects in normal-tension glaucoma patients.
AB  - PURPOSE: To investigate the progression rates of superior and inferior hemifield
      defects and each hemifield in bihemifield defects in normal-tension glaucoma
      patients and to compare the progression rates of each hemifield between groups in
      eyes with similar baseline hemifield defects. DESIGN: Retrospective,
      observational cohort study. METHODS: Medical records of 142 normal-tension
      glaucoma patients who performed more than 5 reliable standard visual field tests
      with superior (group 2; n = 51), inferior (group 1; n = 44), or both hemifield
      (group 3; n = 47) defects were analyzed retrospectively. The changes in the mean
      thresholds of the 10 zones of the glaucoma hemifield test and the entire
      hemifield were inspected. A linear mixed effect model was used with age, gender,
      initial intraocular pressure, mean deviation, and pattern standard deviation
      controlled. RESULTS: There were no significant differences in age and systemic
      and ocular factors between groups except for female gender, which showed a
      significant difference among the 3 groups (P = .032). The progression rate in
      group 2 was significantly faster than in group 1 (-0.713 dB/year vs -0.516
      dB/year; P = .019), especially in central and nasal zones or than in the superior
      hemifield of group 3 (-0.717 dB/year vs -0.470 dB/year; P = .001). There was no
      significant difference in the progression rates between group 1 and the inferior
      hemifield in group 3 (-0.508 dB/year vs -0.441 dB/year; P = .312) or between the
      superior and inferior hemifields in group 3 (-0.468 dB/year vs -0.442 dB/year; P
      = .662). CONCLUSIONS: More careful examination and caution is required in the
      treatment of normal-tension glaucoma patients with superior hemifield defect.

PMID- 22959362
TI  - Persistent corneal edema after collagen cross-linking for keratoconus.
AB  - PURPOSE: To present a new complication of persistent corneal edema after collagen
      cross-linking (CXL) in keratoconus patients. DESIGN: Retrospective case series of
      postoperative corneal edema after CXL. METHODS: study population: All patients
      who underwent CXL treatment with subsequent corneal edema. Patients with stromal
      haze were excluded. intervention: The CXL treatments used the Dresden protocol
      with corneal thickness of more than 400 MUm after epithelium was removed. main
      outcome measure: The resolution of corneal edema after surgery. RESULTS:
      Postoperative corneal edema was identified in 10 (2.9%) of 350 patients who were
      followed up for a mean of 14 +/- 4 months. The edema started on postoperative day
      1 (10/10) and increased for 3 weeks. Additional findings included: deep
      vascularization (2 eyes; 20%), iris atrophy (6 eyes; 60%), pigment dispersion (5
      eyes; 50%), persistent epithelial defect (3 eyes; 30%), and infectious keratitis
      (1 eye; 10%). Specular microscopy was unsuccessful, but the fellow untreated eyes
      had normal endothelial counts. Intraocular pressure and lenticular evaluations
      were normal. Corneal edema improved in 4 patients and resolved in 1 patient. In
      these 5 patients, the logarithm of the minimal angle of resolution best-corrected
      visual acuity was 0.5 +/- 0.18. Penetrating keratoplasty was offered to 5
      patients when improvement plateaued at 3 months, but only 2 patients underwent
      penetrating keratoplasty. CONCLUSIONS: CXL is a safe and effective procedure with
      few known side effects. This case series reports the possibility of corneal
      endothelial damage with visually significant corneal edema after CXL treatment.
      Based on the extent of endothelial damage, patients may require penetrating
      keratoplasty.

PMID- 22959363
TI  - Readability assessment of online patient education materials from academic
      otolaryngology-head and neck surgery departments.
AB  - PURPOSE: The aim of this study was to compare the readability of online patient
      education materials among academic otolaryngology departments in the mid-Atlantic
      region, with the purpose of determining whether these commonly used online
      resources were written at a level readily understood by the average American.
      METHODS: A readability analysis of online patient education materials was
      performed using several commonly used readability assessments including the
      Flesch Reading Ease Score, the Flesch-Kincaid Grade Level, Simple Measure of
      Gobbledygook, Gunning Frequency of Gobbledygook, the New Dale-Chall Test, the
      Coleman-Liau Index, the New Fog Count, the Raygor Readability Estimate, the
      FORCAST test, and the Fry Graph. RESULTS: Most patient education materials from
      these programs were written at or above an 11th grade reading level, considerably
      above National Institutes of Health guidelines for recommended difficulty.
      CONCLUSIONS: Patient educational materials from academic otolaryngology Web sites
      are written at too difficult a reading level for a significant portion of
      patients and can be simplified.

PMID- 22959365
TI  - Radiotherapy for pleomorphic adenoma.
AB  - PURPOSE: The aim of this study was to update our experience in treating
      pleomorphic adenoma with radiotherapy (RT). MATERIALS AND METHODS: This is a
      retrospective analysis of 25 patients treated with RT alone (2 patients) or
      combined with surgery (23 patients), with follow-up ranging from 1.8 to 34.9
      years (median, 10.5 years). RESULTS: Local control was achieved in 13 (75%) of 16
      patients with subclinical disease and 5 (56%) of 9 patients with gross disease.
      Overall local control was achieved in 18 (72%) of 25 patients. The 5-, 10-, and
      15-year overall local control rates were 76 %, 76%, and 68%, respectively. Ten
      patients died of the following causes: recurrent disease, 2; malignant
      transformation, 2; and intercurrent disease, 6. At last follow-up, 14 patients
      were alive without evidence of disease, and 1 patient was alive with disease.
      Dental carries and transient facial nerve deficits were the most common
      complications. No patients developed severe complications subsequent to RT.
      CONCLUSIONS: In patients at high risk for developing recurrent pleomorphic
      adenoma after surgery, RT is effective in controlling subclinical disease.

PMID- 22959366
TI  - Determination of amantadine and rimantadine using a sensitive fluorescent probe.
AB  - Amantadine hydrochloride (AMA) and rimantadine hydrochloride (RIM) are non
      fluorescent in aqueous solutions. This property makes their determination through
      direct fluorescent method difficult. The competing reactions and the
      supramolecular interaction mechanisms between the two drugs and coptisine (COP)
      as they fight for occupancy of the cucurbit[7]uril (CB[7]) cavity, were studied
      using spectrofluorimetry, (1)H NMR, and molecular modeling calculations. Based on
      the significant quenching of the supramolecular complex fluorescence intensity, a
      fluorescent probe method of high sensitivity and selectivity was developed to
      determine AMA or RIM in their pharmaceutical dosage forms and in urine samples
      with good precision and accuracy. The linear range of the method was from 0.0040
      to 1.0 MUg mL(-1) with a detection limit ranging from 0.0012 to 0.0013 MUg mL(
      1). This shows that the proposed method has promising potential for therapeutic
      monitoring and pharmacokinetics and for clinical application.

PMID- 22959364
TI  - Reciprocal roles of STAT3 and STAT5 in nasal polyposis.
AB  - PURPOSE: Nasal polyposis (NP) is a chronic inflammatory disease that is
      characterized by increased populations of Th17 cells and impairment of Treg cells
      function in Chinese patients. Recent studies have shown that signal transducer
      and activator of transcription 3 (STAT3) and STAT5 are indispensable in the
      development and maintenance of Th17 and Treg cells. We investigated the roles of
      STAT3 and STAT5 in the imbalance of Th17 and Treg cells in NP. MATERIALS AND
      METHODS: The levels of IL-6, IL-2, pSTAT3, pSTAT5, SOCS3, RORc, Foxp3, IL-17A,
      and TGF-beta1 were measured in patients with atopic NP, patients with nonatopic
      NP, and controls. We also evaluated the local distribution of Th17 and Treg cells
      by double immunofluorescence staining and the correlations between activated
      STAT3/STAT5 and Th17/Treg cell development were assessed. RESULTS: Increased
      levels of IL-6, pSTAT3, SCOS3, RORc, IL-17A, and CD4(+) RORc(+) cells, and
      decreased levels of IL-2, pSTAT5, Foxp3, TGF-beta1, and CD4(+) Foxp3(+) cells
      were detected in both NP groups compared to controls (P < .05). The differences
      in all expression levels (except for IL-6) were significant between atopic and
      nonatopic patients (P < .05). There was a positive correlation between
      pSTAT3/pSTAT5 levels and Th17/Treg development and a negative correlation between
      SOCS3 and pSTAT3 in NP (P < 0.01). CONCLUSIONS: The results suggest that STAT3
      and STAT5 may function through the IL-6 and IL-2 pathways to play a role in the
      imbalance of Th17/Treg in NP. An even more exaggerated imbalance of Th17/Treg
      caused by atopy may be correlated to the improper ratio of activated STAT3/STAT5.

PMID- 22959367
TI  - The influence of metabolic syndrome on hemodialysis access patency.
AB  - OBJECTIVE: The natural history of patients with metabolic syndrome (MetS)
      undergoing hemodialysis access placement is unknown. MetS has previously been
      found as a risk factor for poor outcomes for vascular surgery patients undergoing
      other interventions. The aim of this is study is to describe the outcomes of MetS
      patients undergoing primary hemodialysis access placement. METHODS: The medical
      records of the 187 patients who underwent hemodialysis access placement between
      1999 and 2009 at the Veterans Administration Connecticut Healthcare System were
      reviewed. Survival, primary patency, and secondary patency were evaluated using
      the Gehan-Breslow test for survival. MetS was defined as the presence of three or
      more of the following: blood pressure>=130/90 mm Hg; triglycerides>=150 mg/dL;
      high-density lipoprotein<=50 mg/dL for women and <=40 mg/dL for men; body mass
      index>=30 kg/m2; or fasting blood glucose>=110 mg/dL. RESULTS: Of the 187
      patients who underwent hemodialysis access placement, 115 (61%) were identified
      to have MetS. The distribution of MetS factors among all patients was
      hypertension in 98%, diabetes in 58%, elevated triclyceride in 39%, decreased
      high-density lipoprotein in 60%, elevated body mass index in 36%, and 39% were
      currently receiving hemodialysis. Patients were a mean age of 66 years. The
      median length of follow-up was 4.2 years. The forearm was site of fistula
      placement in 53%; no difference existed between groups (MetS, 57%; no MetS, 50%;
      P=.388). The median time to primary failure was 0.46 years for all patients
      (MetS, 0.555 years; no MetS, 0.436 years; P=.255). Secondary patency was 50% at
      1.18 years for all patients (no MetS, 1.94 years; MetS, 0.72 years; P=.024).
      Median survival duration for all patients was 4.15 years (no MetS, 5.07 years;
      MetS, 3.63 years; P=.019). CONCLUSIONS: MetS is prevalent among patients
      undergoing hemodialysis access placement. Patients with MetS have equivalent
      primary patency rates; however, their survival and cumulative patency rates are
      significantly lower than in patients without MetS. Patients with MetS form a high
      risk group that needs intensive surveillance protocols.

PMID- 22959368
TI  - The struggle for universal health coverage.

PMID- 22959369
TI  - Safeguarding male circumcision.

PMID- 22959370
TI  - The future of the Global Fund.

PMID- 22959371
TI  - Universal health coverage: the third global health transition?

PMID- 22959372
TI  - Universal health coverage: good health, good economics.

PMID- 22959373
TI  - Universal health coverage is a development issue.

PMID- 22959374
TI  - The shock of the new--cigarette pack warnings.

PMID- 22959376
TI  - Margaret Chan: committed to universal health coverage.

PMID- 22959377
TI  - Minimally invasive versus open oesophagectomy for oesophageal cancer.

PMID- 22959378
TI  - Minimally invasive versus open oesophagectomy for oesophageal cancer.

PMID- 22959379
TI  - Minimally invasive versus open oesophagectomy for oesophageal cancer.

PMID- 22959380
TI  - Minimally invasive versus open oesophagectomy for oesophageal cancer.

PMID- 22959381
TI  - Minimally invasive versus open oesophagectomy for oesophageal cancer.

PMID- 22959383
TI  - Cervical pessary in pregnant women with a short cervix.

PMID- 22959384
TI  - Cervical pessary in pregnant women with a short cervix.

PMID- 22959386
TI  - Cervical pessary in pregnant women with a short cervix.

PMID- 22959387
TI  - Civil society organisations and universal health care.

PMID- 22959388
TI  - Does progress towards universal health coverage improve population health?
AB  - Many commentators, including WHO, have advocated progress towards universal
      health coverage on the grounds that it leads to improvements in population
      health. In this report we review the most robust cross-country empirical evidence
      on the links between expansions in coverage and population health outcomes, with
      a focus on the health effects of extended risk pooling and prepayment as key
      indicators of progress towards universal coverage across health systems. The
      evidence suggests that broader health coverage generally leads to better access
      to necessary care and improved population health, particularly for poor people.
      However, the available evidence base is limited by data and methodological
      constraints, and further research is needed to understand better the ways in
      which the effectiveness of extended health coverage can be maximised, including
      the effects of factors such as the quality of institutions and governance.

PMID- 22959389
TI  - Political and economic aspects of the transition to universal health coverage.
AB  - Countries have reached universal health coverage by different paths and with
      varying health systems. Nonetheless, the trajectory toward universal health
      coverage regularly has three common features. The first is a political process
      driven by a variety of social forces to create public programmes or regulations
      that expand access to care, improve equity, and pool financial risks. The second
      is a growth in incomes and a concomitant rise in health spending, which buys more
      health services for more people. The third is an increase in the share of health
      spending that is pooled rather than paid out-of-pocket by households. This pooled
      share is sometimes mobilised as taxes and channelled through governments that
      provide or subsidise care--in other cases it is mobilised in the form of
      contributions to mandatory insurance schemes. The predominance of pooled spending
      is a necessary condition (but not sufficient) for achieving universal health
      coverage. This paper describes common patterns in countries that have
      successfully provided universal access to health care and considers how economic
      growth, demographics, technology, politics, and health spending have intersected
      to bring about this major development in public health.

PMID- 22959390
TI  - Moving towards universal health coverage: health insurance reforms in nine
      developing countries in Africa and Asia.
AB  - We analyse nine low-income and lower-middle-income countries in Africa and Asia
      that have implemented national health insurance reforms designed to move towards
      universal health coverage. Using the functions-of-health-systems framework, we
      describe these countries' approaches to raising prepaid revenues, pooling risk,
      and purchasing services. Then, using the coverage-box framework, we assess their
      progress across three dimensions of coverage: who, what services, and what
      proportion of health costs are covered. We identify some patterns in the
      structure of these countries' reforms, such as use of tax revenues to subsidise
      target populations, steps towards broader risk pools, and emphasis on purchasing
      services through demand-side financing mechanisms. However, none of the reforms
      purely conform to common health-system archetypes, nor are they identical to each
      other. We report some trends in these countries' progress towards universal
      coverage, such as increasing enrolment in government health insurance, a movement
      towards expanded benefits packages, and decreasing out-of-pocket spending
      accompanied by increasing government share of spending on health. Common,
      comparable indicators of progress towards universal coverage are needed to enable
      countries undergoing reforms to assess outcomes and make midcourse corrections in
      policy and implementation.

PMID- 22959391
TI  - Achieving universal health coverage in low-income settings.

PMID- 22959392
TI  - Falling down and following up.

PMID- 22959393
TI  - Hand hygiene compliance and environmental determinants in child day care centers:
      an observational study.
AB  - BACKGROUND: Children attending day care centers (DCCs) are at high risk for
      contracting infections, for which hand hygiene (HH) is an effective prevention
      measure. The study objectives were to assess caregivers' compliance to HH
      guidelines in DCCs and to identify environmental determinants of HH behavior.
      METHODS: We observed caregivers' compliance to HH guidelines and collected data
      on environmental determinants (ie, number of sinks, number and type of towel and
      soap facilities, availability of alcohol-based hand sanitizers). Using multilevel
      logistic regression analyses, odds ratios (OR) with 95% confidence intervals (CI)
      were obtained for environmental determinants of HH behavior. RESULTS: In 122
      participating DCCs, 350 caregivers and 2,003 HH opportunities were observed. The
      overall compliance was 42% (95% CI: 40%-44%). Compliance for different activities
      for which HH was indicated ranged from 20% to 79%. In the multivariable model,
      the number of towel facilities per caregiver (OR, 2.33; 95% CI: 1.40-3.88) and
      type of towel facilities were significantly associated with HH. Hands were most
      frequently washed when only paper towels were available compared to only fabric
      towels (OR, 1.47; 95% CI: 1.00-2.16) or a combination of both paper and fabric
      towels (OR, 2.13; 95% CI: 1.32-3.44). CONCLUSION: HH compliance of caregivers in
      Dutch child DCCs can be improved. Interventions for this should take into account
      environmental determinants such as the number and type of towel facilities.

PMID- 22959394
TI  - Protection against neonatal Escherichia coli diarrhea by vaccination of sows with
      a novel multivalent vaccine candidate expressing E. coli adhesins associated with
      neonatal pig colibacillosis.
AB  - In this study, we investigated the optimal condition of a novel multivalent
      Escherichia coli vaccine candidate for protection efficacy against E. coli
      colibacillosis in piglets via booster strategy using oral and intramuscular
      administration routes. The candidate was constructed using an expression and
      secretion plasmid and an attenuated Salmonella delivery system as described
      earlier. Pregnant sows were divided into four groups of three sows each and
      immunized with a mixture of the individual vaccine strains. Sows were primed and
      boosted at 8 and 11 weeks of pregnancy. Group A sows were primed intramuscularly
      and boosted orally. Group B sows were primed and boosted orally. Group C sows
      were orally primed and intramuscularly boosted. Group D sows were primed and
      boosted with PBS as a control. The serum IgG and IgA levels to individual adhesin
      antigens were elevated in immunized sows compared to controls, as were colostral
      IgA and IgG levels of all immunized sows. In addition, serum IgG and IgA levels
      in piglets from all immunized sows were significantly increased. These data
      suggest that systemic and colostral immune responses were highly induced by
      vaccination with the candidate. After challenge with a virulent strain of E.
      coli, clinical signs such as diarrhea and mortality were not observed in suckling
      piglets from the immunized sows, while diarrhea and mortality affected 100% and
      25% of the control group piglets, respectively. These findings indicate that
      immunization of sows with the candidate vaccine irrespective of administration
      routes can effectively protect their piglets against neonatal E. coli diarrhea.

PMID- 22959395
TI  - Pre-operative CT coronary angiography in patients with mitral valve prolapse
      referred for surgical repair: comparison of accuracy, radiation dose and cost
      versus invasive coronary angiography.
AB  - BACKGROUND: The aims of this study are to evaluate the accuracy of low dose
      multidetector computed tomography coronary angiography (MDCT) versus invasive
      coronary angiography (ICA) in ruling out CAD in patients with mitral valve
      prolapse and severe mitral regurgitation (MVP) before cardiac surgery and to
      compare the overall effective radiation dose (ED) and cost of a diagnostic
      approach in which conventional ICA should be performed only in patients with
      significant CAD as detected by MDCT. METHODS: Eighty patients with MVP and
      without history of CAD were randomized to MDCT (Group 1) or ICA (Group 2) to rule
      out CAD before surgery. However, ICA was also performed as gold standard
      reference in Group 1 to test the diagnostic accuracy of MDCT. A diagnostic work
      up A in whom all patients underwent low-dose MDCT as initial diagnostic test and
      those with positive findings were referred for ICA was compared with work-up B in
      which all patients were referred for ICA according to the standard of care in
      terms of ED and cost. RESULTS: The two groups were homogeneous in terms of
      gender, age and body mass index. The overall feasibility and accuracy in a
      patient-based model were 99% and 93%, respectively. The overall ED and costs were
      significantly lower in diagnostic work-up A compared to diagnostic work-up B.
      CONCLUSIONS: The accuracy of low dose MDCT for ruling out the presence of
      significant CAD in patients undergoing elective valve surgery for mitral valve
      prolapse is excellent with a reduction of overall radiation dose exposure and
      costs.

PMID- 22959396
TI  - Structured contraceptive counseling provided by the Contraceptive CHOICE Project.
AB  - BACKGROUND: We describe the contraceptive counseling provided by the
      Contraceptive CHOICE Project (CHOICE) and compare contraceptive methods selected
      between the university research site and community partner clinics. STUDY DESIGN:
      We developed a structured, contraceptive counseling program. All CHOICE
      participants enrolling at our university research site underwent the counseling,
      which was evidence-based and included information about all reversible
      contraception. Participants enrolling at partner clinics underwent "usual"
      counseling. We trained 54 research team members to provide contraceptive
      counseling; the majority had no formal health care training. We compared the
      contraceptive methods chosen by participants enrolling at our university research
      site to participants enrolling at partner clinics who did not undergo structured
      contraceptive counseling. RESULTS: There were 6,530 (86%) women who enrolled into
      CHOICE at our university site and 1,107 (14%) women who enrolled at partner
      clinics. Uptake of long-acting reversible contraception was high at both the
      university site and partner clinics (72% and 78%, respectively, p<.0001).
      However, uptake of the intrauterine device was higher at the university site (58%
      compared to 43%, p<.0001) and uptake of the subdermal implant was higher at
      partner clinics (35% versus 14%, p<.0001). After adjusting for confounders, we
      found no difference in the uptake of long-acting reversible contraception between
      women counseled at the university site compared to partner clinics (adjusted
      relative risk=0.98, 95% confidence interval [0.94, 1.02]). CONCLUSION: Structured
      contraceptive counseling can be effectively provided in a clinical research
      setting by staff without prior health care experience or clinical training.

PMID- 22959397
TI  - An improved model of care for inflammatory bowel disease (IBD).

PMID- 22959398
TI  - High-definition endoscopic imaging with i-Scan for the detection and
      characterization of duodenal Crohn's disease.

PMID- 22959399
TI  - Risk factors for peristomal pyoderma gangrenosum complicating inflammatory bowel
      disease.
AB  - BACKGROUND AND AIMS: Risk factors for peristomal pyoderma gangrenosum (PPG) are
      not well defined. The aim of this study was to evaluate risk factors associated
      with development of PPG. METHODS: Both PPG patients and controls were obtained by
      searching a database of the Cleveland Clinic using the ICD-9 code from March 2005
      to May 2011. The control group was selected by matching for underlying diseases
      and type of stoma in a ratio of 3:1. Univariate and multivariate analyses were
      performed. RESULTS: A total of 15 PPG cases and 45 controls were included. The
      mean age at the time of PPG diagnosis was 46.0 +/- 14.4 years. The underlying
      disease was Crohn's disease in 7 patients (46.7%), ulcerative colitis in 7
      (46.7%) and indeterminate colitis in 1 (6.7%). Eleven patients (73.3%) had end
      ileostomy, 3 (20.0%) had loop ileostomy and 1 (6.7%) had colostomy. Eleven
      patients (73.3%) had active intestinal disease. In multivariate analysis, female
      gender, the presence of concurrent autoimmune disorders, and a high body mass
      index (BMI) were significantly associated with the presence of PPG, with odds
      ratios of 8.385 (95% confidence interval [CI]: 1.496-46.982, p=0.015), 6.882 (95%
      CI:1.438-32.941, p=0.016), and 9.895 (95% CI: 1.970-43.704, p=0.005),
      respectively. After a median follow-up of 12.8 (interquartile range: 7.9-20.1)
      months with appropriate therapy, PPG healed in 8 patients (53.3%) and improved in
      7 (46.7%) patients, after treatment. CONCLUSIONS: Female gender, the presence of
      autoimmune disorders and a high BMI appeared to be associated with an increased
      risk for the development of PPG in IBD patients.

PMID- 22959400
TI  - Primary malignant esophageal melanoma arising from localized benign
      melanocytosis.
AB  - A heavy drinker and smoker had a normal UGI-endoscopy in 1996. In 1999, a repeat
      examination disclosed distal esophageal benign melanocytosis, typical, macro- and
      microscopically. Endoscopic and microscopic features were stable in 2002 and
      2004. In 2007, dysphagia prompted an endoscopy, which disclosed a poorly
      differentiated epidermoid carcinoma at 19 cm and black nodules of the cardia with
      a microscopy typical of malignant melanoma, uT3N1 at EUS. Radiochemotherapy led
      to an 8-month improvement, which did not prevent death one year after diagnosis.

PMID- 22959401
TI  - Pregnancy associated pancreatitis revisited.
AB  - OBJECTIVES: To evaluate the demographics, risk factors and outcomes of pregnancy
      associated pancreatitis (PAP). STUDY DESIGN: A retrospective chart review was
      done using ICD-9 Code 577.0 (acute pancreatitis) from January 2005 through
      December 2009. Women aged 18 to 45 years, who were pregnant and 6 months after
      delivery were considered for the study. For each case, two women of the same age
      (+/- 4 years) with no history of pancreatitis were matched as control.
      Demographics, etiology, diagnostic modality and intervention were obtained.
      RESULTS: During the 5 years of study, 29 cases of PAP occurred among 25,600 total
      hospital deliveries, yielding prevalence of 0.001%: Hispanics 48%, Caucasians
      24%, African Americans 17.2%, and Asian/Pacific Islanders 13% (P<0.05). Sixty
      five percent of those with pre-pregnancy body mass index (BMI) more than 30
      kg/m(2) had PAP, versus 24% with BMI between 25 and 30 kg/m(2) and 10% with BMI
      less than 25 kg/m(2) (P<0.05). An increasing trend of PAP was seen with
      gestational age and number of pregnancy. CONCLUSION: Gallstone disease is the
      most frequent etiology for PAP and tends to occur more often in Hispanics in New
      Jersey.

PMID- 22959402
TI  - How product trial changes quality perception of four new processed beef products.
AB  - The purpose of this paper is the quantitative analysis of the change in quality
      perception of four new processed beef products from pre to post trial phases.
      Based on the Total Food Quality Model, differences in pre and post-trial phases
      were measured using repeated measures technique for cue evaluation, quality
      evaluation and purchase motive fulfillment. For two of the tested products, trial
      resulted in a decline of the evaluation of cues, quality and purchase motive
      fulfillment compared to pre-trial expectations. For these products, positive
      expectations were created by giving information about ingredients and ways of
      processing, which were not confirmed during trial. For the other two products,
      evaluations on key sensory dimensions based on trial exceeded expectations,
      whereas the other evaluations remained unchanged. Several demographic factors
      influenced the pattern of results, notably age and gender, which may be due to
      underlying differences in previous experience. The study gives useful insights
      for testing of new processed meat products before market introduction.

PMID- 22959404
TI  - Dynamic capsuloligamentous anatomy of the glenohumeral joint.
AB  - Though many anatomic and biomechanical studies have been performed to elucidate
      capsuloligamentous anatomy of the glenohumeral joint, no previous studies have
      evaluated capsuloligamentous anatomy during rotator cuff contraction. The purpose
      of this study was to define and document the orientation and interrelationship
      between the glenohumeral ligaments during simulated rotator cuff contraction. Six
      fresh cadaveric shoulders were arthroscoped to document and grade ligamentous
      anatomy. The superior and middle glenohumeral ligaments and the anterior and
      posterior bands of the inferior glenohumeral ligament complex were labeled by an
      arthroscopicassisted technique with a linked metallic bead system. Shoulders were
      then placed onto an experimental apparatus that simulated rotator cuff function
      through computer-controlled servo-hydrolic actuators attached to the rotator cuff
      and biceps by a clamp and cable-and-pulley system. Simulated rotator cuff action
      and manual placement allowed shoulders to be placed into three positions of
      rotation (neutral, internal, and external) in three positions of scapular plane
      abduction (0 degrees , 45 degrees , 90 degrees ). Anteroposterior and axillary
      lateral plane radiographs were taken in each position to document orientation of
      all four ligaments. Both the superior and middle glenohumeral ligaments were
      maximally lengthened in 0 degrees  and 45 degrees  abduction and external
      rotation and appeared to shorten in all positions of abduction. The anterior and
      posterior bands of the inferior glenohumeral ligament complex maintained a
      cruciate orientation in all positions of abduction in the anteroposterior plane,
      except at 90 degrees  abduction and external rotation, where they are parallel.
      This cruciate orientation is due to the different location of the glenoid origin
      and humeral insertion of each band and may allow reciprocal tightening of each
      during rotation. The glenohumeral capsule is composed of discreet ligaments that
      undergo large charges in orientation during rotation. The superior and middle
      glenohumeral ligaments appear to complement the inferior glenohumeral ligaments,
      with the former tightening in adduction and the latter tightening in abduction.
      This relationship permits the large range of motion normally seen in the
      glenohumeral joint.

PMID- 22959405
TI  - The influence of abductor lever-arm changes after shoulder arthroplasty.
AB  - Clinically, pain relief is usually satisfactory after shoulder arthroplasty, but
      the range of motion can be limited. The changes of the lever-arms of deltoid and
      supraspinatus muscles are considered to be important factors influencing
      postoperative active motion. After excluding patients with muscle weakness
      resulting from a neurologic condition, patients with chronic rotator-cuff tears,
      patients who did not follow rehabilitation guidelines, and patients with
      bilateral arthroplasties, 22 arthroplasty cases remained and were evaluated.
      Compared with the unaffected side, four radiologic parameters were assessed: (A)
      offset of humeral head, (B) lateralization of humeral head, (C) acromiohumeral
      interval, and (D) superoinferior migration of humeral head. The differences were
      measured and statistically analyzed. In summary: (1) The active and passive range
      of motion of abduction in scapular plane were 89.5 degrees  +/- 26.1 degrees  and
      109.7 degrees  +/- 25.0 degrees . (2) Parameters A, B, and C statistically
      changed (p < 0.05). (3) B value of the operated side was reduced below zero in
      six (27.3%). (4) There was a tendency to create medial shifting and inferior
      subluxation with the arthroplasty. This had a moderate adverse correlation to the
      active range of motion (correlation coefficient 0.498). (5) Before normalization
      for bone size, only C as a single parameter had moderate correlation with motion;
      after normalization, this decreased. (6) If combined parameters were assessed, A
      + C had a moderate correlation (correlation coefficient 0.435) with motion. (7)
      If an accurate anatomic relationship cannot be completely restored, A seemed more
      significant than any other parameters (p = 0.002); namely, shoulders with a
      smaller offset had a more limited active range of motion in abduction.

PMID- 22959403
TI  - Move in for the kill: motile microtubule regulators.
AB  - The stereotypical function of kinesin superfamily motors is to transport cargo
      along microtubules. However, some kinesins also shape the microtubule track by
      regulating microtubule assembly and disassembly. Recent work has shown that the
      kinesin-8 family of motors emerge as key regulators of cellular microtubule
      length. The studied kinesin-8s are highly processive motors that walk towards the
      microtubule plus-end. Once at plus-ends, they have complex effects on polymer
      dynamics; kinesin-8s either destabilize or stabilize microtubules, depending on
      the context. This review focuses on the mechanisms underlying kinesin-8
      microtubule interactions and microtubule length control. We compare and contrast
      kinesin-8s with the other major microtubule-regulating kinesins (kinesin-4 and
      kinesin-13), to survey the current understanding of the diverse ways that
      kinesins control microtubule dynamics.

PMID- 22959406
TI  - The glenohumeral offset ratio: A radiographic study.
AB  - A systematic method of component selection for total shoulder arthroplasty is
      needed. The method must take into account the soft-tissue constraints of a
      degenerative joint and optimize joint biomechanics by placing the joint line in
      the best possible position. The purpose of our study was to determine
      radiographically the normal glenohumeral joint line position based on a ratio of
      distances between the joint line and fixed landmarks on the humerus and scapula.
      We studied modified anteroposterior radiographs of the glenohumeral joint in 86
      volunteers (51 men and 35 women; ages ranging from 21 to 47 years). Two
      measurements were made on each radiograph: (1) the perpendicular distance from
      the most medial portion of the glenoid to the inferior base of the coracoid
      process at its attachment to the scapular blade, and (2) the perpendicular
      distance from the midline of the humeral shaft to the most medial point on the
      humeral head. The joint line position was described as the ratio of the glenoid
      measurement to the sum of the two measurements (i.e., the glenohumeral offset
      ratio). The validity and reliability of glenoid offset measurements were
      determined by comparing radiographic and anatomic measurements of glenoid offset
      in cadaveric human scapulae. Radiographs were made with rotational error to
      determine its effects on the measurement of humeral offset. Humeral offsets and
      glenoid thicknesses of five different total shoulder systems were then determined
      from template overlays. The mean glenohumeral offset ratio was 0.31 (range 0.18
      to 0.39). We detected no significant difference in the ratio between men and
      women volunteers. There was close agreement between radiographie and direct
      (anatomic) measurements of glenoid offset in cadaveric scapulae. Values for
      humeral offset were not significantly affected by radiographic rotational error.
      The evidence indicates that a fairly constant glenohumeral offset ratio in normal
      shoulders can be reliably calculated from a single radiograph. In addition to the
      prosthesis specifications, we suggest that the glenohumeral offset ratio is a
      potentially useful preoperative planning tool for total shoulder arthroplasty.

PMID- 22959407
TI  - Arthroscopic repair of superior glenoid labral detachment (the SLAP lesion).
AB  - Complete detachment of the glenoid labrum from the superior pole of the glenoid,
      which is associated with a destabilization of the origin of the long biceps
      tendon, leads to altered function in the shoulder joint. This is especially
      noticeable when the shoulder is used in overhead activities. Two operative
      techniques are described for reattachment of the glenoid labrum to the glenoid.
      In the first six patients the glenoid labrum was reattached with small cannulated
      titanium screws. In five patients these screws were inserted under arthroscopic
      control from a cranial direction. The labrum was always reattached just behind
      the origin of the long biceps tendon. The most favorable portal was identified by
      percutaneous probing with a Kirschner wire. If the superior glenoid pole could
      not be reached via a portal placed anterior or medial to the acromion, a hole was
      drilled through the acromion, and a transacromial approach was used. The screws
      were removed by arthroscopy after 3 to 5 months. In the last eight patients,
      absorbable tacks were used instead of screws. Of 18 patients who showed a
      complete detachment of the glenoid labrum from the superior pole of the glenoid
      with destabilization of the attachment of the biceps tendon, 14 underwent
      reattachment as described previously. The minimum follow-up time was greater than
      6 months (mean follow-up time 18 months, maximum follow-up time 30 months). At
      follow-up, eight patients felt completely rehabilitated and had resumed their
      previous overhead activities (overhead sports). Four patients believed their
      conditions were improved. Two patients had not experienced any improvement. Of
      the patients who had not undergone reattachment and who had undergone shaving of
      the free margin of the glenoid labrum, only one had experienced improvement,
      while the other three patients did not report any improvement.

PMID- 22959408
TI  - Magnetic resonance imaging of rotator cuff tearing and degenerative tendon
      changes: Correlation with histologic pathology.
AB  - We studied degeneration of the torn rotator cuff by comparing the signal
      intensity of the torn tendon edge on magnetic resonance imaging with cellularity
      of the tendon. Fifty-one shoulders with rotator cuff tears requiring surgical
      repairs were scanned before surgery in a 0.5T magnetic resonance imaging system.
      T1-, T2-, T2*-, and proton-density-weighted sequences were obtained. Three
      specimens from the torn tendon edge that were obtained at operation were examined
      microscopically, and the number of tendon cells was calculated and averaged.
      Degeneration of the torn rotator cuff edge was associated with an increase in
      signal intensity of the torn tendon edge on T1 -, T2-, T2*, and proton-density
      weighted images and a decrease in tendon cellularity. The T2-, T2*-, and proton
      density-weighted images were more useful, because on the T1 -weighted image it
      was difficult to identify the torn cuff edge.

PMID- 22959409
TI  - Stabilizers of the elbow.
AB  - The elbow joint is stabilized by the conforming shape of its articular surfaces,
      by the joint capsule and collateral ligaments, and by muscles that pass across
      the joint. Each of these static and dynamic stabilizers serve to keep the joint
      surfaces in apposition. The relative contribution of these structures to
      stability varies as a function of joint orientation and the extent of muscle
      activation. In this article our present understanding of the stabilizers of the
      elbow is reviewed. Important implications regarding the management of osseous and
      ligamentous injuries about the elbow are highlighted.

PMID- 22959410
TI  - Cell death features induced in Leishmania major by 1,3,4-thiadiazole derivatives.
AB  - Under a variety of stress conditions, Leishmania species display some
      morphological and biochemical features characteristic of mammalian programmed
      cell death or necrosis. Nitroheteroaryl-1,3,4-thiadiazoles induce cell death in
      Leishmania major (L. major). Putative mechanisms of action of these compounds
      were investigated in vitro at cellular and molecular levels. We used colorimetric
      assay to measure acid phosphatase activity which is an indicator of cell
      viability in the promastigotes. The mode of toxicity was determined by detection
      of phosphatidylserine translocation to the surface, evaluation of cell membrane
      integrity, and in situ dUTP nick end-labeling assay. We also determined poly-ADP
      ribose polymerase-like protein (PARP) level in the parasites after treatment. A
      significant reduction of acid phosphatase level, one of the most crucial and
      virulent factors of the parasite was found in parasites treated with 1,3,4
      thiadiazole derivatives. In addition, 1,3,4-thiadiazole derivatives induced loss
      of plasma membrane integrity, DNA breakage, proteolysis of PARP and necrotic-like
      death in the parasites.

PMID- 22959411
TI  - On the fitness of microbial taxonomy.
AB  - Microbial taxonomy seems to be an expanding discipline especially in Asian
      countries. By contrast, the number of taxonomists in Western countries are in
      decline, and the reasons for this could either be economic or due to interest.
      Losing taxonomy expertise could have consequences for Western countries.

PMID- 22959413
TI  - Who's covering our loved ones: surprising barriers in the sign-out process.
AB  - BACKGROUND: The aims of this study were to characterize obstacles affecting
      current sign-out practices and to evaluate the potential impact of standardized
      sign-out guidelines. METHODS: In June 2011, detailed guidelines for transitions
      of care were implemented, and a 29-item multiple-choice survey was developed to
      assess sign-out practices, attitudes, and barriers to effective communication.
      Surveys were administered to residents and nurses at 3 time points. Comparisons
      between time points were assessed using t tests and chi(2) tests (alpha = .05).
      RESULTS: Guideline implementation achieved nonsignificant improvements in
      satisfaction with sign-outs, perceptions of patient safety, adequacy of
      information provided in sign-out, and patient knowledge by on-call residents. On
      follow-up, concerns surfaced regarding less complete sign-out processes due to
      new duty-hour restrictions. CONCLUSIONS: Guideline implementation mildly improved
      perceptions of safety and adequacy of sign-out; however, persistent barriers to
      continuity of care remain. Sign-out standardization may not adequately ensure
      patient safety, and further efforts to improve handoff processes are in need.

PMID- 22959412
TI  - Calreticulin in the immune system: ins and outs.
AB  - Calreticulin is a calcium-binding chaperone that has several functions in the
      immune response. In the endoplasmic reticulum (ER), calreticulin facilitates the
      folding of major histocompatibility complex (MHC) class I molecules and their
      assembly factor tapasin, thereby influencing antigen presentation to cytotoxic T
      cells. Although calreticulin is normally ER-resident, it is found at the cell
      surface of living cancer cells and dying cells. Here, calreticulin promotes
      cellular phagocytic uptake. In tumor vaccine models, drugs that induce cell
      surface calreticulin confer enhanced tumor protection in an extracellular
      calreticulin-dependent manner. Much remains to be understood about the roles of
      calreticulin in these distinct functions. Further investigations are important
      towards advancing basic knowledge of glycoprotein-folding pathways, and towards
      developing new cancer therapeutic strategies.

PMID- 22959414
TI  - Neurophysiological, behavioural and perceptual differences between wrist flexion
      and extension related to sensorimotor monitoring as shown by corticomuscular
      coherence.
AB  - OBJECTIVE: To investigate the effects of neurophysiological, behavioural and
      perceptual differences between wrist flexion and extension movements, on their
      corticomuscular coherence (CMC) levels. METHODS: CMC was calculated between
      simultaneously recorded electroencephalography (EEG) and electromyography (EMG)
      measures from fifteen healthy subjects who performed 10 repetitions of
      alternating isometric wrist flexion and extension tasks at 15% of their maximum
      voluntary contraction (MVC) torque levels. Task precision was calculated from
      torque recordings. Subjects rated the perceived difficulty levels for both tasks.
      RESULTS: Flexors had significantly lower; peak beta CMC, peak frequency,
      frequency width, normalised EMG beta power, torque fluctuation (<5 Hz and beta
      band) and perceived difficulty ratings; but higher MVC and precision compared to
      extensors. EEG alpha and beta powers were non-different between flexion and
      extension. CONCLUSIONS: An inverse relationship between CMC and motor precision
      was found in our inter-muscle study, contrary to the direct relationship found in
      a prior intra-muscle study. Functional suitability, long term usage adaptation
      and lower perceived difficulty of wrist flexion may explain the results.
      SIGNIFICANCE: We extend the CMC literature to include the clinically different,
      antagonistic wrist flexors and extensors and add to the debate relating CMC and
      motor precision by positing the confounding effect of perceived difficulty.

PMID- 22959415
TI  - An analysis of the kangaroo care intervention using neonatal EEG complexity: a
      preliminary study.
AB  - OBJECTIVE: Skin-to-skin contact (SSC) promotes physiological stability and
      interaction between parents and infants. Temporal analyses of predictability in
      EEG-sleep time series can elucidate functional brain maturation between SSC and
      non-SSC cohorts at similar post-menstrual ages (PMAs). METHODS: Sixteen EEG-sleep
      studies were performed on eight preterm infants who received 8 weeks of SSC, and
      compared with two non-SSC cohorts at term (N=126) that include a preterm group
      corrected to term age and a full term group. Two time series measures of
      predictability were used for comparisons. RESULTS: The SSC premature neonate
      group had increased complexity when compared to the non-SSC premature neonate
      group at the same PMA. Discriminant analysis shows that SSC neonates at 40 weeks
      PMA are closer to the full term neonate non-SSC group than to the premature non
      SSC group at the same PMA; suggesting that the KC intervention accelerates
      neurophysiological maturation of premature neonates. CONCLUSIONS: Based on the
      hypothesis that EEG-derived complexity increases with neurophysiological
      maturation as supported by previously published research, SSC accelerates brain
      maturation in healthy preterm infants as quantified by time series measures of
      predictability when compared to a similar non-SSC group. SIGNIFICANCE: Times
      series methods that quantify predictability of EEG sleep in neonates can provide
      useful information about altered neural development after developmental care
      interventions such as SSC. Analyses of this type may be helpful in assessing
      other neuroprotection strategies.

PMID- 22959416
TI  - Phantom tumour of the lung.

PMID- 22959417
TI  - Structural aspects of mitochondrial translational apparatus.
AB  - During the last decade groundbreaking progress has been made towards the
      understanding of structure and function of cell's translational machinery. Cryo
      electron microscopic (cryo-EM) and X-ray crystallographic structures of
      cytoplasmic ribosomes from several bacterial and eukaryotic species are now
      available in various ligand-bound states. Significant advances have also been
      made in structural studies on ribosomes of the cellular organelles, such as those
      present in the chloroplasts and mitochondria, using cryo-EM techniques. Here we
      review the progress made in structure determination of the mitochondrial
      ribosomes, with an emphasis on the mammalian mitochondrial ribosome and one of
      its translation initiation factors, and discuss challenges that lie ahead in
      obtaining their high-resolution structures.

PMID- 22959418
TI  - A case of bupropion-induced stuttering.
AB  - OBJECTIVE: Stuttering is a frequent side effect of many psychotropic drugs,
      particularly antidepressants. METHOD: This is a case report of a woman presenting
      with stuttering after starting bupropion treatment for her depression. RESULTS:
      The patient's stuttering resolved after discontinuing the bupropion. CONCLUSION:
      Neuroimaging and pharmacological studies have implicated dopamine in the
      pathophysiology of stuttering. Bupropion's ability to increase dopamine in the
      frontal cortex was suspected to have been involved in this patient's stuttering.
      However, further research is needed before causality can be assured.

PMID- 22959419
TI  - Carisoprodol: an underrecognized drug of abuse in north India.
AB  - BACKGROUND: There is limited literature on clinical profile of subjects abusing
      carisoprodol. METHODS: Our series of 34 subjects shows that a typical subject was
      an unmarried, unemployed, urban resident from a nuclear family set up; was a
      substance abuser before being introduced to carisoprodol by another substance
      abuser; initiated the use to get a better "kick" and after regular use reported
      craving and withdrawal symptoms. RESULTS: The effect of carisoprodol was dose
      dependent: a majority reported a feeling of general wellbeing on consuming up to
      three tablets; a hypomanic state with 4-10 tablets and confusion, disorientation
      and drowsiness with >10 tablets at a time. CONCLUSION: Thus being an
      underrecognized drug of abuse, carisoprodol is in need of wider awareness and
      regulatory measures to prevent its emergence as a greater menace in the future.

PMID- 22959420
TI  - Feasibility and acceptability of interventions to delay gun access in VA mental
      health settings.
AB  - OBJECTIVES: The majority of VA patient suicides are completed with firearms.
      Interventions that delay patients' gun access during high-risk periods may reduce
      suicide, but may not be acceptable to VA stakeholders or may be challenging to
      implement. Using qualitative methods, stakeholders' perceptions about gun safety
      and interventions to delay gun access during high-risk periods were explored.
      METHODS: Ten focus groups and four individual interviews were conducted with key
      stakeholders, including VA mental health patients, mental health clinicians,
      family members and VA facility leaders (N=60). Transcripts were consensus-coded
      by two independent coders, and structured summaries were developed and reviewed
      using a consensus process. RESULTS: All stakeholder groups indicated that VA
      health system providers had a role in increasing patient safety and emphasized
      the need for providers to address gun access with their at-risk patients.
      However, VA mental health patients and clinicians reported limited discussion
      regarding gun access in VA mental health settings during routine care. Most,
      although not all, patients and clinicians indicated that routine screening for
      gun access was acceptable, with several noting that it was more acceptable for
      mental health patients. Most participants suggested that family and friends be
      involved in reducing gun access, but expressed concerns about potential family
      member safety. Participants generally found distribution of trigger locks
      acceptable, but were skeptical about its effectiveness. Involving Veteran Service
      Organizations or other individuals in temporarily holding guns during high-risk
      periods was acceptable to many participants but only with numerous caveats.
      CONCLUSIONS: Patients, clinicians and family members consider the VA health
      system to have a legitimate role in addressing gun safety. Several measures to
      delay gun access during high-risk periods for suicide were seen as acceptable and
      feasible if implemented thoughtfully.

PMID- 22959421
TI  - Tacrolimus-induced paranoid delusions and fugue-like state.
AB  - We report the case of a 43 year old male with no prior psychiatric history with
      apparent tacrolimus-induced psychosis. Previous reports have identified other
      neurotoxic adverse effects due to tacrolimus, however, to our knowledge, there
      are few reports that describe psychosis induced by the immunosuppressant drug.
      Although psychosis may be a rare adverse effect, it can have significant impact
      on the long-term prognosis and treatment in transplant recipients. It is
      imperative to quickly identify patients who develop a mental status change while
      on tacrolimus and to work with the appropriate transplant team in managing these
      patients. Treatment usually calls for prompt discontinuation of tacrolimus,
      substituting with another immunosuppressant, and possible use of antipsychotics.

PMID- 22959423
TI  - Young-onset multiple system atrophy.

PMID- 22959422
TI  - Prescribed opioid difficulties, depression and opioid dose among chronic opioid
      therapy patients.
AB  - BACKGROUND: Chronic opioid therapy has increased dramatically, as have
      complications related to prescription opioids. Little is known about the problems
      and concerns attributed to opioids by patients receiving different opioid doses.
      METHODS: We surveyed 1883 patients who were receiving chronic opioid therapy for
      chronic noncancer pain. Opioid regimen characteristics were ascertained from
      electronic pharmacy records. Patient-reported opioid-related problems and
      concerns were measured using the Prescription Opioid Difficulties Scale.
      Depression was assessed with the Patient Health Questionnaire. RESULTS: Patients
      prescribed higher opioid doses reported modestly higher pain intensity and pain
      impact. After adjustment, patients on higher doses attributed higher levels of
      psychosocial problems and control concerns to prescribed opioids (P<.0001). They
      also had higher levels of depression and were more likely to meet criteria for
      clinical depression. Over 60% of patients receiving 120+ mg daily (morphine
      equivalent) were clinically depressed, a 2.6-fold higher risk (95% confidence
      interval: 1.5-4.4) than patients on low-dose regimens (<20 mg daily).
      CONCLUSIONS: Higher opioid doses were associated with somewhat higher pain
      severity and higher levels of patient-reported opioid-related psychosocial
      problems, control concerns and depression. These findings may result from patient
      selection for high-dose therapy or problems caused by higher-dose opioids.

PMID- 22959424
TI  - Preoperative antibiotic prophylaxis in the penicillin-allergic patient.

PMID- 22959425
TI  - [Transparency of the health system: accountability is no longer an option].

PMID- 22959426
TI  - [Bithalamic infarction secondary to Percheron's artery occlusion: Difficulties in
      diagnosis and management in intensive care medicine].

PMID- 22959427
TI  - Descriptive and social network analysis of pig transport data recorded by quality
      assured pig farms in the UK.
AB  - The aim of this study was to examine farm-to-farm pig movement connections, and
      the usage of hauliers and abattoirs, for farms in the United Kingdom (UK), to
      determine the interconnectivity of the pig farm network and the implications this
      may have for the transmission and control of Salmonella, which was chosen as an
      example of an important endemic disease. Data were collected from three Quality
      Assurance Schemes on the use of abattoirs and livestock hauliers by commercial
      pig farms, and the supply of pigs to and from farms. The observed dataset had
      considerable variability in the number of direct (farm-to-farm) and indirect (via
      hauliers or abattoirs) connections between each farm over a 12-month period. The
      use of multiple hauliers and abattoirs by many farms resulted in considerable
      interconnectivity between farms due to these indirect routes. The network
      displayed a higher level of clustering, and short network distances between
      farms, than that shown by equivalent randomly generated datasets, indicating that
      infectious diseases might transmit quickly amongst farms but within certain
      clusters of farms, thus limiting the total number of farms affected. This
      structure and the occurrence of multiple indirect routes between many pairs of
      farms (via pig movements to other interconnected farms or from hauliers used by
      both farms), may indicate that targeting surveillance and controls on those farms
      with high network centrality characteristics (degree, betweenness) alone would
      not prove effective. Encouraging all farms within the network to reduce the
      number of connections might be a useful way of reducing Salmonella prevalence as
      it would reduce the effect of high prevalence on other farms within the network.
      The analysis also highlighted differences in the connections between geographical
      regions that were used to discuss the comparatively low Salmonella prevalence in
      Scotland detected by previous studies. Farms identified as belonging to large
      companies, as categorised by our analysis, were shown to mostly have movement
      connections within that company. However, small company farms had connections to
      farms belonging to large companies or other small companies, demonstrating that
      they may play an important role in creating links between large companies. The
      majority of farms in both Scotland and North-East and Eastern England belonged to
      large companies, and this finding is discussed in relation to how this may help
      explain the lower Salmonella seroprevalence in these areas. The study provides a
      first description of the characteristics of the UK pig movement network and the
      analysis has indicated a number of findings that might have implications for
      disease transmission and targeting surveillance and control.

PMID- 22959428
TI  - A prospective study on fitness, workload and reasons for premature training ends
      and temporary training breaks in two groups of riding horses.
AB  - Little is known about wastage in riding horses and the factors like fitness and
      workload that may reduce injuries and maximise welfare. To evaluate fitness,
      workload and reasons for premature training ends (PTEs) and temporary training
      breaks (TTBs) during a nine week training period, two groups of riding horses
      were used: Group A consisting of 58 horses used for student equitation courses
      (32 with training prior to admission and 26 without) and Group B consisting of 26
      horses owned by two riding schools (school-I and school-II). To assess fitness,
      all horses performed a standardised exercise test (SET) at the start (SET-I) and
      end of the training period (SET-II) measuring heart rate (HR bpm) and speed
      (m/s). In addition, all horses were monitored daily during the training period
      for their health and workload. In Group A, trained horses had significantly lower
      HRs in SET-I (P=0.05) compared to untrained horses and in SET-II, trained horses
      tended to have lower HRs than untrained horses, though this was not statistically
      significant (P=0.057). During the training period all horses received an
      identical workload. A total of 19.0% of Group A horses ended the training period
      prematurely for veterinary reasons (PTEV); of those untrained horses had earlier
      a PTEV in the training period (after 2.8 +/- 1.3 weeks) than trained horses
      (after 4.1 +/- 1.5 weeks, P=0.030). In Group B, school-I and school-II horses did
      not differ significantly in fitness level nor in workload. More school-II horses
      ended the training period prematurely for veterinary reasons (n=7; 70%) compared
      to school-I horses (n=4; 25%, P=0.032), although seven (63.6%) of these horses
      were still continuously used in riding lessons. In both groups (A and B), small
      injuries (without a temporary training break) were significantly associated with
      premature training ends for veterinary reasons later on: in Group A small
      injuries preceded 27.3% of the PTEVs (P=0.005) and in Group B small injuries
      preceded 54.5% of the PTEVs (P=0.030). In conclusion, as all horses in each
      subgroup had the same workload, the occurrence of PTEV seemed not associated with
      the workload. In Group A horses, level of fitness seems to be an important factor
      for the point in time injuries will occur during the training period. In all
      horses, injuries were more likely when a temporary training break was not taken
      following seemingly minor injuries. Since a lot of injured Group B horses were
      used in riding lessons against veterinary advice, this may indicate that riding
      school owners have different perception on welfare and if true this may cause
      serious welfare problems.

PMID- 22959429
TI  - Risk mapping of heart and skeletal muscle inflammation in salmon farming.
AB  - Heart and skeletal muscle inflammation (HSMI) is an infectious disease causing
      losses to the Norwegian salmon farming industry due to increased mortality and
      high morbidity in infected salmon. The disease is listed as a notifiable disease
      on list 3 (national list) by the Norwegian Food Safety Authority. HSMI is
      believed to be a viral disease, but the association to the recently discovered
      Piscine reovirus (PRV) remains unclear. Undoubtedly, other factors interact to
      determine whether PRV-infected fish develop disease or not. In this study,
      logistic regression was used to model the risk of an outbreak of HSMI at the
      cohort level, by including spatio-temporal risk factors. The data consisted of
      fish cohorts grown on geo-referenced farms from 2002 to 2010. The risk factors
      included were: infection pressure, cohort size (maximum number of fish), cohort
      index (smolt characteristics), cohort lifespan (months in sea) and a geo-index
      calculated as the position along a local polynomial regression line based on the
      longitude and latitude of each farm included in the study. The results showed
      that the risk of developing HSMI increased with increasing cohort lifespan,
      increasing infection pressure and increasing cohort size, and was mostly low for
      cohorts grown on farms in Southern-Norway, high for farms in Mid-Norway and
      variable for farms in Northern-Norway (based on the geo-index). The final model
      was used to explore three different scenarios with regards to the risk of
      developing HSMI, and to calculate the probability for each cohort of developing
      HSMI, independent of their actual disease-status. The model suggested that the
      probability of developing HSMI was much higher in Mid-Norway than in the rest of
      the country. Even though PRV seems to be widely distributed in the environment,
      the finding that infection pressure has a large influence on the probability of
      developing HSMI, suggests that it might be possible to reduce the number of
      clinical outbreaks, if measures are taken to reduce infection pressure. However,
      the prospects of controlling the spread of HSMI and reducing clinical outbreaks
      might be difficult because of indications of large distance spread of the
      disease.

PMID- 22959430
TI  - Computer-aided analysis of airway trees in micro-CT scans of ex vivo porcine lung
      tissue.
AB  - We present a highly automated approach to obtain detailed structural models of
      airway trees from ex vivo porcine lung tissue imaged with a high resolution micro
      CT scanner. Such information is an important prerequisite to systematically study
      models of lung disease that affect airway morphology. The method initially
      identifies all tubular airway-like structures in the lung. In a second processing
      step, these structures are grouped into a connected airway tree by utilizing
      prior knowledge about the airway trees branching pattern. The method was
      evaluated on 12 micro-CT scans from four tracheal lobes of piglets imaged at
      three different inflation levels. For this study, two control piglets and two
      cystic fibrosis piglets were used. For systematic validation of our approach, an
      airway nomenclature was developed for the pig airway tree. Out of more than 3500
      airway tree segments assessed during evaluation, 88.45% were correctly identified
      by the method. No false positive airway branches were found. A detailed
      performance analysis for different airway tree hierarchy levels, lung inflation
      levels and piglets with/without cystic fibrosis is presented in the paper.

PMID- 22959431
TI  - Clinical image: Spondylodiscitis due to a fistula between L5-S1 disc and colon.

PMID- 22959432
TI  - CWC22 connects pre-mRNA splicing and exon junction complex assembly.
AB  - The exon junction complex (EJC) is a key regulator of posttranscriptional mRNA
      fate and binds to mRNA during splicing. Although the composition of EJCs is well
      understood, the mechanism mediating splicing-dependent EJC assembly and the
      factor(s) recruiting the EJC remain elusive. Here, we identify CWC22 as an
      essential splicing factor that is required for EJC assembly. In CWC22-depleted
      cells, pre-mRNA splicing is impaired but is rescued by a central fragment of
      CWC22. We show that the MIF4G domain of CWC22 initiates EJC assembly via a direct
      interaction with the EJC core protein eIF4A3, and we characterize mutations in
      eIF4A3 that abolish binding to CWC22. These eIF4A3 mutants efficiently nucleate
      splicing-independent recombinant EJC core complexes, but they fail to support
      splicing-dependent EJC deposition. Our work establishes a direct link between the
      splicing machinery and the EJC, hence uncovering a molecular interaction at the
      center of a posttranscriptional gene regulation network.

PMID- 22959433
TI  - Immune tolerance to tumor antigens occurs in a specialized environment of the
      spleen.
AB  - Peripheral tolerance to tumor antigens (Ags) is a major hurdle for antitumor
      immunity. Draining lymph nodes are considered the privileged sites for Ag
      presentation to T cells and for the onset of peripheral tolerance. Here, we show
      that the spleen is fundamentally important for tumor-induced tolerance.
      Splenectomy restores lymphocyte function and induces tumor regression when
      coupled with immunotherapy. Splenic CD11b(+)Gr-1(int)Ly6C(hi) cells, mostly
      comprising proliferating CCR2(+)-inflammatory monocytes with features of myeloid
      progenitors, expand in the marginal zone of the spleen. Here, they alter the
      normal tissue cytoarchitecture and closely associate with memory CD8(+) T cells,
      cross-presenting tumor Ags and causing their tolerization. Because of its high
      proliferative potential, this myeloid cell subset is also susceptible to low-dose
      chemotherapy, which can be exploited as an adjuvant to passive immunotherapy.
      CCL2 serum levels in cancer patients are directly related to the accumulation of
      immature myeloid cells and are predictive for overall survival in patients who
      develop a multipeptide response to cancer vaccines.

PMID- 22959434
TI  - Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of
      oxidative DNA lesions in neural progenitor cells.
AB  - Accumulation of oxidative DNA damage has been proposed as a potential cause of
      age-related cognitive decline. The major pathway for removal of oxidative DNA
      base lesions is base excision repair, which is initiated by DNA glycosylases. In
      mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single
      stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult
      neurogenesis is crucial for maintenance of hippocampus-dependent functions
      involved in behavior. Herein, behavioral studies reveal learning and memory
      deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural
      stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative
      capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in
      Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent
      repair of oxidative DNA damage in neural stem/progenitor cells is required for
      maintenance of adult neurogenesis to counteract the age-associated deterioration
      of cognitive performance.

PMID- 22959435
TI  - POSH localizes activated Rac1 to control the formation of cytoplasmic dilation of
      the leading process and neuronal migration.
AB  - The formation of proximal cytoplasmic dilation in the leading process (PCDLP) of
      migratory neocortical neurons is crucial for somal translocation and neuronal
      migration, processes that require the elaborate coordination of F-actin dynamics,
      centrosomal movement, and nucleokinesis. However, the underlying molecular
      mechanisms remain poorly understood. Here, we show that the Rac1-interacting
      scaffold protein POSH is essential for neuronal migration in vivo. We demonstrate
      that POSH is concentrated in the PCDLP and that knockdown of POSH impairs PCDLP
      formation, centrosome translocation, and nucleokinesis. Furthermore, POSH
      colocalizes with F-actin and the activated form of Rac1. Knockdown of POSH
      impairs F-actin assembly and delocalizes activated Rac1. Interference of Rac1
      activity also disrupts F-actin assembly and PCDLP formation and perturbs neuronal
      migration. Thus, we have uncovered a mechanism by which POSH regulates the
      localization of activated Rac1 and F-actin assembly to control PCDLP formation
      and subsequent somal translocation of migratory neurons.

PMID- 22959437
TI  - [Contribution of magnetic resonance imaging in diagnosis of pericardial
      mesothelioma: a case report].
AB  - Pericardial mesothelioma is a rare form of pericardial tumor. The invasive
      investigations such as biopsy make the diagnosis. Non-invasive imaging techniques
      provide valuable information about its diagnosis and its clinical impact. We
      report here the results of magnetic resonance imaging of pericardial mesothelioma
      in a 65-year-old woman. The originality and purpose of this case is to illustrate
      the additional value of magnetic resonance imaging that should be systematically
      performed when assessing this pathology.

PMID- 22959436
TI  - Structural basis for a reciprocal regulation between SCF and CSN.
AB  - Skp1-Cul1-Fbox (SCF) E3 ligases are activated by ligation to the ubiquitin-like
      protein Nedd8, which is reversed by the deneddylating Cop9 signalosome (CSN).
      However, CSN also promotes SCF substrate turnover through unknown mechanisms.
      Through biochemical and electron microscopy analyses, we determined molecular
      models of CSN complexes with SCF(Skp2/Cks1) and SCF(Fbw7) and found that CSN
      occludes both SCF functional sites-the catalytic Rbx1-Cul1 C-terminal domain and
      the substrate receptor. Indeed, CSN binding prevents SCF interactions with E2
      enzymes and a ubiquitination substrate, and it inhibits SCF-catalyzed ubiquitin
      chain formation independent of deneddylation. Importantly, CSN prevents
      neddylation of the bound cullin, unless binding of a ubiquitination substrate
      triggers SCF dissociation and neddylation. Taken together, the results provide a
      model for how reciprocal regulation sensitizes CSN to the SCF assembly state and
      inhibits a catalytically competent SCF until a ubiquitination substrate drives
      its own degradation by displacing CSN, thereby promoting cullin neddylation and
      substrate ubiquitination.

PMID- 22959438
TI  - [Sudden death during sport activity in Tunisia: autopsy study in 32 cases].
AB  - PURPOSE: To develop profile of the victims and to study circumstances, causes of
      death and autopsy findings. METHODS: Retrospective study of cases of sudden death
      in sport activity whose autopsy was performed in forensic department of Tunis,
      between January 2005 and December 2009. RESULTS: During study period, 32 cases of
      SD in sport activity were recorded. These are amateur athletes predominantly male
      (84% of cases). Victims are aged between 15 and 79 years with an average age of
      about 33.16 years. Young subjects whose age is less than 35 years representing
      68.7% of cases. 9.3% of victims had a family history of SD and 18.7% of cases had
      a known cardiac history. The sports most involved are running (40.6% of cases),
      football (31.3% of cases) and dance (12.5% of cases). Sixty-nine percent of
      victims died during sports activities. Presence of witnesses was noted in all
      cases; however, none of these witnesses has begun resuscitation. Cause of death
      was cardiac in 84.4% of cases. In young athletes, hypertrophic cardiomyopathy is
      the leading cause (nine cases), followed by arrhythmogenic right ventricular
      dysplasia (three cases). Among other causes, there is the myocardial bridge,
      congenital anomalies of the coronary arteries, aortic dissection and dilated
      cardiomyopathy. Beyond 35 years, coronary artery diseases represent the cause of
      death (nine cases). Only case of death secondary to non-cardiac disease occurred
      after a severe asthma attack. In four cases (12.5%), no cause of death was
      identified after a complete autopsy accompanied by further investigations. The
      cause of the death was imputed to a rhythmic pathology. CONCLUSION: This is the
      first study dealing with autopsy in SD in sport have provided a specific profile
      of victims. Other studies on larger samples and using standardized autopsy
      protocols are needed.

PMID- 22959439
TI  - [Immediate results of repeat percutaneous mitral valvuloplasty].
AB  - Percutaneous mitral valvuloplasty (PMV) has emerged as the procedure of choice in
      treatment of mitral stenosis and has proved effectiveness in cases of mitral
      restenosis after surgical commissurotomy. However, this technique is costly, is
      not devoid of complication and success is not guaranteed. Indications of an
      attempted redo percutaneous mitral valvuloplasty (redo-PMV) are not well
      established. Hence the idea to study the immediate results of (re-PMV). PURPOSE
      OF WORK: The purpose of this study is to evaluate the immediate results of the re
      PMV in patients with mitral restenosis and analyze the different clinical and
      laboratory findings to determine predictors of success of re-PMV to better
      selection of candidates for a new attempt PMV. METHODS: Retrospective study from
      a series of 40 procedures of re-PMV with the Inoue balloon succeeding a
      successful initial procedure, collected in the cardiology department of Habib
      Thameur hospital of Tunis between 1996 and 2011, in which we identified the data
      of clinical and paraclinical examinations. RESULTS: The mean age of patients was
      43 +/- 11 years [23; 63]. Of the population, 87.5% were female (five men and 35
      women). The average time between the two procedures was 8 +/- 4 years [1; 15].
      The immediate procedural success defined by a mitral valve area greater or equal
      to 1.5 cm(2) and a grade less than or equal to 2 mitral regurgitation was
      obtained in 31 patients (77.5%). A severe mitral regurgitation (MR) was observed
      in three patients (7.5%). A cerebrovascular stroke occurred in one patient
      (2.5%). No death or cardiac tamponade were noted. Class III or IV of NYHA, a pre
      procedural MR, pulmonary hypertension and an overall score of Padial greater than
      10 were retained as predictors of failure. More the overall score of Wilkins is
      high (>8), more it is predictive of failure. The two components of the Wilkins
      score: valvular mobility and subvalvular apparatus (SVA) and the parameter of the
      redesign of the SVA score of Padial considered separately are also predictive of
      failure. Only a left atrial area less than or equal to 25 cm(2) was linked to
      high risk of severe MR. CONCLUSION: Redo percutaneous mitral valvuloplasty is a
      therapeutic alternative to surgery that is effective and promising interesting
      immediate results. Analysis of clinical and mainly echographic parameters is
      useful for predicting the success of the gesture, which will allow a better
      selection of candidates for re-PMV.

PMID- 22959440
TI  - [Low dose cardiac computed tomography: how to obtain it?].
AB  - Since the introduction of Multi-slice computed tomography (CT), cardiac CT has
      been the increasingly used as a noninvasive modality for the diagnosis of
      coronary disease. Despite its potential benefits and promising clinical results,
      it has suffered from high doses of radiation associated with a risk of radiation
      induced cancers. This has raised serious concerns in clinical practice. A number
      of strategies were then implemented to reduce the radiation dose associated with
      cardiac CT. The aim of this review is not to compare doses of different CT
      systems available on the market but to present an overview of different
      approaches to dose reduction and future directions.

PMID- 22959441
TI  - [Coronary artery spasm during dobutamine stress echocardiography: prevalence,
      clinical and echocardiographic characteristics and prognosis].
AB  - OBJECTIVES: To assess the prevalence of coronary artery spasm during dobutamine
      stress chocardiography (DSE), to describe clinical and echocardiographic
      characteristics and prognosis. PATIENTS AND METHODS: We evaluated all the
      patients with known or suspected coronary artery disease (CAD) referred to our
      echocardiography laboratory for dobutamine stress test between January 2004 and
      June 2012, (10013 exams). Those with abnormal DSE underwent coronary angiograms
      with a systematic methylergometrine intracoronary injection in case of absence of
      significant coronary stenosis or spontaneous occlusive coronary spasm. Patients
      who had spontaneous occlusive coronary spasm or positive methylergometrine test
      but no significant stenoses were included. RESULTS: One thousand and four
      patients had abnormal DSE, 78 (7.7%) fulfilled the inclusion criteria. There were
      57 males and 21 females, mean age was 57.9 years, 37 patients had a known history
      of CAD. Twenty-four patients had a spasm on the left anterior artery (31%), 37 on
      the right coronary artery (47%) and 17 on the circumflex (22%). There was a good
      correlation between spastic arteries and dobutamine induced wall motion
      abnormalities territories. No complications occurred during the exams or during
      the provocation test. After 46 months mean follow up; one case of myocardial
      infarction with normal coronary arteries was noted and six patients experienced
      recurrent angina responding to treatment intensification. CONCLUSION: Coronary
      artery spasm during DSE but is a rare and under-diagnosed finding; it has,
      though, to be recognized as it may partly explain some erroneously labelled
      "false positive" exams. Methylergometrine provocation test should be performed in
      such a situation to establish the diagnosis. Prognosis appears favourable.

PMID- 22959442
TI  - [Contribution of Doppler echocardiography in the diagnosis of arrhythmogenic
      right ventricular dysplasia].
AB  - The arrhythmogenic right ventricular dysplasia (ARVD) is a rare heart muscle
      disorder, occurring typically in young adults. The diagnosis remains difficult.
      The aim of our study was to evaluate the contribution of Doppler echocardiography
      in the diagnosis and screening for ARVD. Eighteen patients, followed in our
      cardiology department for ARVD and 10 "witnesses" in good condition were
      evaluated by echocardiography. We have essentially clarified the dimensions of
      the RV, its kinetics segmental, Doppler tricuspid flow, the study of movement of
      the tricuspid annulus in M-mode and tissue Doppler. We have compared the results
      of echocardiography at those of MRI and RV angiography. In our series,
      pathological measurement of the RV was found in all patients. No one of the
      control group had expansion of the RV. Twelve of our patients had abnormal wall
      motion. The displacement of the tricuspid annulus is reduced both in septal and
      lateral position. In tissue Doppler, Ea/Aa was lower than in healthy subjects in
      15 cases in the lateral position and 16 cases in septal position. ETT is superior
      to MRI and RV angiography in the diagnosis of localized forms. The family survey,
      conducted in 38 parents of eight consenting families allowed to screen seven
      subjects. All these patients had abnormal Doppler echocardiography. Doppler
      echocardiography is a reliable and efficient investigation for the diagnosis of
      ARVD. It remains on the first intention to review a suspected ARVD.

PMID- 22959443
TI  - [Non-invasive coronary flow reserve is an independent predictor of exercise
      capacity after acute anterior myocardial infarction].
AB  - BACKGROUND: After acute myocardial infarction (MI) coronary microvascular
      impairment and reduced exercise capacity are both determinant of prognosis.
      OBJECTIVE: We tested whether non-invasive coronary flow reserve (CFR) performed
      after MI predicts post-MI exercise capacity (EC). METHODS: Fifty consecutive
      patients (pts) (mean age 56.5+/-11years, 30% women) with a first reperfused ST
      elevation anterior MI, and sustained TIMI 3 flow after mechanical reperfusion,
      underwent prospectively non-invasive CFR in the distal part of the left anterior
      descending artery (LAD), using intravenous adenosine infusion (0.14mg/kg per
      minute, within 2min), within 24h after successful primary coronary angioplasty
      (CFR 1), and 4+/-1.6months later after a period of convalescence and a cardiac
      rehabilitation program (CFR 2). CFR was defined as peak hyperaemic LAD flow
      velocity divided by baseline flow velocity. All pts also underwent semi-supine
      exercise stress echocardiography (ESE) the same day of CFR 2. ESE was performed
      at an initial workload of 25-30watts with a 20watts increase at 2-minute
      intervals. Beta-blockers were withheld 24h before ESE. RESULTS: The mean CFR 2
      increased significantly when compared to CFR 1 (2.9+/-0.65 versus 1.9+/-0.4,
      P<0.01). During ESE, percentage of maximal predict heart rate achieved was 82+/
      12%, maximal workload 95+/-30watts, exercise duration 486+/-155s, the ratio of
      double product 3.1+/-0.8, and EC 5.8+/-1.1 metabolic equivalents. No ischemia was
      induced during ESE in all pts, and the degree of mitral regurgitation did not
      differ significantly between rest and exercise. CFR 2 was significantly
      correlated to all indices related to EC (all, P<0.01), whereas CFR 1 was
      correlated to LV systolic function at follow-up (P<0.05) but not to EC. In
      multivariate analysis including age, sex, and body mass index, CFR 2 remained an
      independent predictor of EC (P<0.01). CONCLUSION: Contrarily to acute CFR, CFR at
      follow-up is an independent predictor of EC after reperfused anterior MI. This
      suggests that the improvement of the coronary microcirculation is closely linked
      to the physical aptitude after MI.

PMID- 22959444
TI  - Single-step production of polyhydroxybutyrate from starch by using alpha-amylase
      cell-surface displaying system of Corynebacterium glutamicum.
AB  - Direct polyhydroxybutyrate (PHB) production from starch was for the first time
      achieved using engineered Corynebacterium glutamicum expressing PHB biosynthetic
      genes and displaying alpha-amylase on its cell surface. The engineered strain
      accumulated 6.4 wt% PHB from starch which was higher than that obtained from
      glucose (4.9 wt%).

PMID- 22959445
TI  - Primary intrasellar schwannoma.
AB  - Intracranial schwannomas commonly arise from the eighth cranial nerve in the
      cerebellopontine angle. Schwannoma arising in the sella and extending into the
      suprasellar region is very rare and is easily mistaken for pituitary adenoma. To
      our knowledge, there have been only 12 previous reports. We present a patient
      with primary intrasellar schwannoma that clinically and radiologically resembled
      a pituitary adenoma (PA). Intra-operative findings differed from a PA, as the
      tumour had a firmer consistency. Gross total excision of the lesion was done via
      a transethmosphenoidal approach. Post-operatively the patient improved in visual
      acuity and visual fields. We have reviewed the literature and described the
      characteristics of such lesions.

PMID- 22959446
TI  - The role of the superior turbinate flap in skull base reconstruction.
AB  - We describe surgical treatment of a hemangiopericytoma in the anterior skull base
      and nasal cavity. The patient underwent a novel method of anterior skull base
      reconstruction, using the superior turbinate and cerebral falx, which was
      successful. The patient did not develop a cerebrospinal fluid leak or
      intracranial infection.

PMID- 22959447
TI  - Should all patients with mild ischemic stroke be excluded from therapeutic stroke
      trials?
AB  - We aimed to investigate stroke etiology in our cohort of patients with mild
      ischemic stroke (MIS) and to study the effect of stroke etiology on patient
      outcome. We also studied the effect of intravenous (IV) recombinant tissue
      plasminogen activator (rt-PA) in this cohort. We analyzed patients with MIS who
      were eligible for IV rt-PA presenting within 3 hours of symptom onset with a
      National Institutes of Health Stroke Scale (NIHSS) score <= 5 admitted from March
      2006 through June 2009. Stroke etiology was determined using the Trial of Org
      10172 in Acute Stroke Treatment (TOAST) classification. Primary outcome was the
      discharge NIHSS score. We identified 110 patients with MIS with a male-to-female
      ratio of: 1.4:1 and a mean age of 69 +/- 13 years. The mean admission NIHSS score
      was 2 +/- 3. The stroke risk factors were identified as: hypertension, 82
      patients (75%); previous stroke/transient ischemic attack, 36 patients (33%); and
      atrial fibrillation, 28 patients (26%). Stroke etiology was identified as: large
      vessel atherosclerosis (31 patients, 28%), cardioembolism (29, 26%), small vessel
      occlusion (seven, 6%) and those with other or undetermined conditions (43, 39%).
      IV rt-PA was administered to 25 patients (23%). Despite the use of IV rt-PA in
      only one patient with small vessel occlusion, patients in our study with this
      stroke etiology tended to have better outcomes compared to those with other
      stroke subtypes, although the difference was not statistically significant. The
      discharge NIHSS score did not show any statistically significant difference
      between the treated and untreated patients with MIS. Our study shows that MIS may
      be caused by non small vessel occlusion in more patients than previously reported
      and this subgroup of patients with MIS should not be excluded from trials of
      intravenous and endovascular therapies.

PMID- 22959448
TI  - Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection.
      Part 1: Clinical, radiological and pathological studies.
AB  - The intraoperative identification and resection of glioma is a significant and
      important challenge in neurosurgery. Complete resection of the enhancing tumour
      increases the median survival time in glioblastoma compared to partial glioma
      resection; however, it is achieved in fewer than half of eligible patients when
      conventional tumour identification methods are used. Increasing the incidence of
      complete resection, without causing excess morbidity, requires new methods to
      accurately identify neoplastic tissue intraoperatively, such as use of the drug 5
      amino-levulinic acid (ALA). After ALA ingestion, the fluorescent molecule
      protoporphyrin IX (PpIX) accumulates in high grade glioma, allowing the
      neurosurgeon to more easily detect and accurately resect tumour. The utility of
      ALA has been demonstrated in a large, multicentre phase III randomised control
      trial of 243 patients with high grade glioma. ALA use led to a significant
      increase in the incidence of complete resection (65% compared to 36%), improved
      progression-free survival at 6 months (41% compared to 21%), fewer
      reinterventions, and delayed onset of neurological deterioration. This review
      provides a broad assessment of ALA-PpIX fluorescence-guided resection, with Part
      1 focusing on its clinical efficacy, and correlations with imaging and histology.
      The theoretical, biochemical and practical aspects of ALA use are reviewed in
      Part 2.

PMID- 22959449
TI  - Dose issues in antiepileptic therapy.
AB  - Antiepileptic drug (AED) therapy is complex, with numerous traditional drugs and
      more than 10 second-generation drugs being approved since the mid-1990s. The
      burden of epilepsy is compounded by the adverse effects of these drugs, which
      comprise a variety of manifestations, the most devastating of which is their
      association with physical and cognitive foetal malformations in babies exposed to
      these agents in utero. Many effects are dose-related - a clear understanding of
      these adverse effects is desirable to be able to adjust medications and
      medication regimens to suit individual patient needs and to try to prevent them,
      by a careful introduction, slow escalation, well-considered combination and
      possible pre-exposure testing of patients for their tolerance, to each proposed
      AED. The overall problem and the profiles of the main agents are outlined from
      the perspective of dose-related issues.

PMID- 22959451
TI  - Smoking and infertility: a committee opinion.
AB  - Approximately 30% of women of reproductive age and 35% of men of reproductive age
      in the United States smoke cigarettes. Substantial harmful effects of cigarette
      smoke on fecundity and reproduction have become apparent but are not generally
      appreciated. This document replaces the 2008 ASRM Practice Committee document of
      the same name.

PMID- 22959450
TI  - Effects of resveratrol on growth and function of rat ovarian granulosa cells.
AB  - OBJECTIVE: To evaluate the effects of resveratrol on growth and function of
      granulosa cells. Previously, we demonstrated that resveratrol exerts profound
      proapoptotic effects on theca-interstitial cells. DESIGN: In vitro study.
      SETTING: Research laboratory. ANIMAL(S): Immature Sprague-Dawley female rats.
      INTERVENTION(S): Granulosa cells were cultured in the absence or presence of
      resveratrol. MAIN OUTCOME MEASURE(S): DNA synthesis was determined by thymidine
      incorporation assay, apoptosis by activity of caspases 3/7, cell morphology by
      immunocytochemistry, steroidogenesis by mass spectrometry, antimullerian hormone
      (AMH), and vascular endothelial growth factor (VEGF) expression by polymerase
      chain reaction and Western blot. RESULT(S): Resveratrol induced a biphasic effect
      on DNA synthesis, whereby a lower concentration stimulated thymidine
      incorporation and higher concentrations inhibited it. Additionally, resveratrol
      slightly increased the cell number and modestly decreased the activity of
      caspases 3/7 with no effect on cell morphology or progesterone production.
      However, resveratrol decreased aromatization and VEGF expression, whereas AMH
      expression remained unaltered. CONCLUSION(S): Resveratrol, by exerting cytostatic
      but not cytotoxic effects, together with antiangiogenic actions mediated by
      decreased VEGF in granulosa cells, may alter the ratio of theca-to-granulosa
      cells and decrease vascular permeability, and therefore may be of potential
      therapeutic use in conditions associated with highly vascularized theca
      interstitial hyperplasia and abnormal angiogenesis, such as those seen in women
      with polycystic ovary syndrome.

PMID- 22959452
TI  - Safety of uterine and/or ovarian preservation in young women with grade 1
      intramucous endometrial adenocarcinoma: a comparison of survival according to the
      extent of surgery.
AB  - OBJECTIVE: To compare the survival of patients with grade 1 intramucous
      endometrial adenocarcinoma according to the extent of surgery. DESIGN:
      Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A cohort of 489
      patients who were 40 years of age or younger with grade 1 intramucous endometrial
      adenocarcinoma. INTERVENTION(S): The patients were divided into the following
      three groups: 101 patients who underwent uterine preservation, 184 patients who
      underwent ovarian preservation, and 204 patients who underwent hysterectomy with
      oophorectomy. MAIN OUTCOME MEASURE(S): The demographics and survival rates were
      compared. RESULT(S): In the multivariate analysis, no factors were associated
      with ovarian preservation. In the multivariate analysis, the factors that were
      associated with uterine preservation were a later year of diagnosis and young
      age. In a multivariate Cox model, ovarian and uterine preservation had no effect
      on either cancer-specific or overall survival. CONCLUSION(S): In patients with
      grade 1 intramucous endometrial adenocarcinoma, uterine and ovarian preservation
      were not associated with an increase in cancer-related mortality. Longer follow
      up is needed to confirm the safety of a conservative approach toward the ovaries
      and/or the uterus.

PMID- 22959453
TI  - The value of chromosomal analysis in oligozoospermic men.
AB  - OBJECTIVE: To determine the prevalence of chromosomal abnormalities in relation
      to sperm concentration in subfertile oligozoospermic men. DESIGN: Retrospective
      cohort study. SETTING: Two teaching hospitals. PATIENT(S): We retrospectively
      studied all men who received chromosomal analysis prior to intracytoplasmic sperm
      injection (ICSI) treatment from 2000 to 2010 in two teaching hospitals.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The results of chromosomal
      analysis and semen analysis were recorded. The frequency of abnormal karyotypes
      was analyzed in relation to the sperm concentration, categorized as extreme
      oligozoospermia (>0 to <=1 million/mL), severe oligozoospermia (>1 to <=5
      million/mL), moderate oligozoospermia (>5 to <=20 million/mL), or normospermia
      (>20 million/mL). RESULT(S): Among 582 male ICSI candidates, the rates of
      abnormal karyotypes were 1.2% (2/162), 2.2% (5/227), and 1.5% (2/130) for men
      with extreme, severe, and moderate oligozoospermia, respectively. No
      abnormalities were present in normospermic men. CONCLUSION(S): The risk of
      conceiving a viable child with unbalanced structural chromosomal abnormalities in
      men with oligozoospermia may not justify karyotyping.

PMID- 22959454
TI  - Decreased endometrial vascularity in patients with antiphospholipid antibodies
      associated recurrent miscarriage during midluteal phase.
AB  - OBJECTIVE: To explore uterine arterial impedance and endometrial-subendometrial
      vascularity determined by two-dimensional Doppler ultrasonography (2D-DU) and
      three-dimensional ultrasonography and power Doppler angiography (3D-PDA) between
      patients with antiphospholipid antibodies-associated recurrent miscarriage (aPL
      RM) and normal fertile women, and to further investigate the relationship between
      these parameters and endometrial microvessel density (MVD). DESIGN: Prospective
      observational study. SETTING: Tertiary-care fertility center. PATIENT(S): A total
      of 109 aPL-RM patients (aPL-RM group) and 49 normal fertile women (control
      group). INTERVENTION(S): Uterine measurement by transvaginal ultrasonography and
      endometrial MVD in the midluteal phase was assessed for both groups. MAIN OUTCOME
      MEASURE(S): Endometrial thickness, volume, and MVD, uterine arterial pulsatility
      index (PI) and resistance index (RI), and the vascularization index (VI), flow
      index (FI), and vascularization flow index (VFI) of endometrial and
      subendometrial regions were measured on day 7 of a natural cycle after ovulation.
      RESULT(S): Both groups had similar endometrial thickness, volume, and MVD and
      uterine arterial PI and RI. Endometrial VI, FI, VFI, and subendometrial FI were
      significantly reduced in the aPL-RM group compared with the control group. None
      of the uterine arterial 2D-DU and endometrial-subendometrial 3D-PDA parameters
      correlated with the endometrial MVD in both groups. CONCLUSION(S): Endometrial
      and subendometrial vascularity was significantly impaired in aPL-RM patients
      during natural midluteal phase compared with normal fertile women, and
      endometrial MVD did not correlate with any of the acquired vascularity
      parameters.

PMID- 22959455
TI  - Methylation analysis of idiopathic recurrent spontaneous miscarriage cases
      reveals aberrant imprinting at H19 ICR in normozoospermic individuals.
AB  - OBJECTIVE: To study H19 ICR methylation levels in association with sperm
      parameters routinely analyzed in idiopathic recurrent spontaneous miscarriage
      cases. DESIGN: Case-control study. SETTING: Academic research setting.
      PATIENT(S): Male partners of couples with a history of idiopathic recurrent
      spontaneous miscarriage (RSM group) and male partners of couples with proven
      fertility (control group). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Paternal age, sperm concentration, motility, chromatin compaction status,
      morphology, and H19 ICR methylation were assessed in control and idiopathic RSM
      group participants. RESULT(S): Paternal age and basic semen parameters analyzed
      did not show any significant difference between the two groups; however H19 ICR
      methylation levels were reduced significantly in the idiopathic RSM group
      compared with the control group. CONCLUSION(S): Significant reduction in the H19
      ICR methylation without significant difference in the sperm parameters
      demonstrates aberrant imprinting to be associated with idiopathic RSM.

PMID- 22959457
TI  - Intramuscular progesterone versus 8% Crinone vaginal gel for luteal phase support
      for day 3 cryopreserved embryo transfer.
AB  - OBJECTIVE: To compare outcomes after intramuscular progesterone (IMP) or 8%
      Crinone vaginal gel for luteal support for day 3 cryopreserved embryo transfer
      (CET). DESIGN: Retrospective cohort study with multivariable analysis. SETTING:
      Academic medical center. PATIENT(S): All autologous and donor egg in vitro
      fertilization and intracytoplasmic sperm injection patients who had a day 3 CET
      from January 1, 2008, to April 30, 2011, with luteal support using 25-50 mg/d IMP
      or 8% Crinone twice daily, initiated 3 days before the CET. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy, and live
      birth rates per CET. RESULT(S): IMP (n = 440) and Crinone (n = 298) recipients
      were similar for all demographic characteristics and cycle parameters assessed.
      Although implantation rates did not differ significantly between the two groups
      (Crinone vs. IMP: 19.6% vs. 30.4%), women supplemented with Crinone had
      significantly lower rates of clinical pregnancy (36.9% vs. 51.1%) and live birth
      (24.4% vs. 39.1%) compared with those on IMP. CONCLUSION(S): We observed that day
      3 CET cycles with 8% Crinone luteal support had a 44% and 49% lower odds of
      clinical pregnancy and live birth, respectively, compared with those with IMP
      support. Further studies are required to identify the optimal timing and dose of
      8% Crinone vaginal gel for use in CET cycles.

PMID- 22959456
TI  - Differential metabolic profiling of non-pure trisomy 21 human preimplantation
      embryos.
AB  - OBJECTIVE: To investigate the metabolomic signature of trisomy 21 preimplantation
      human embryos by a noninvasive approach using mass spectrometry- (MS-) and
      nuclear magnetic resonance spectroscopy- (NMR-) based metabolic profiling
      platforms. DESIGN: A total of 171 spent media samples were collected from day 3
      embryos and comparatively analyzed by MS analysis (chromosomally normal embryos,
      n = 15; trisomy 21 embryos, n = 15) and a matched control media group (without
      embryo, n = 14) and by NMR spectroscopy (normal embryos, n = 39; trisomy 21
      embryos, n = 35; monosomy 21 embryos, n = 24) and a matched control media group
      (without embryo, n = 29). SETTING: IVF clinic/preimplantation genetic diagnosis
      (PGD) unit facilities. PATIENT(S): One hundred seventy-one spent media samples
      obtained from human IVF embryos from patients included in our PGD program.
      INTERVENTION(S): Metabolomic profiling of embryo spent media using liquid
      chromatography/gas chromatography coupled with MS and NMR. MAIN OUTCOME
      MEASURE(S): Comparative identification of the metabolites present in the spent
      media from normal versus trisomy/monosomy 21 day 3 embryos. RESULT(S): Two
      metabolites, caproate and androsterone sulphate, and two unknown compounds were
      differentially expressed between normal and trisomy 21 day 3 embryos.
      Furthermore, the NMR results indicate that there could be a correlation between
      the differences found between trisomy 21/monosomy 21 and the normal embryos in a
      spectral region compatible with isoleucine. CONCLUSION(S): This study suggests
      that the use of differential metabolomic markers found in spent media from
      preimplantation embryos could be a feasible method for the detection of
      aneuploidies before ET.

PMID- 22959458
TI  - Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary
      syndrome: a systematic review and biomarker database integration.
AB  - OBJECTIVE: To review and identify possible biomarkers for ovarian cancer (OC) in
      women with polycystic ovary syndrome (PCOS). DESIGN: Systematic literature
      searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics,"
      "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers
      for OC were then integrated with an updated previously published database of all
      proteomic biomarkers identified to date in patients with PCOS. SETTING: Academic
      department of obstetrics and gynecology in the United Kingdom. PATIENT(S): A
      total of 180 women identified in the six studies. INTERVENTION(S): Tissue samples
      from women with OC vs. tissue samples from women without OC. MAIN OUTCOME
      MEASURE(S): Proteomic biomarkers, proteomic technique used, and methodologic
      quality score. RESULT(S): A panel of six biomarkers was overexpressed both in
      women with OC and in women with PCOS. These biomarkers include calreticulin,
      fibrinogen-gamma, superoxide dismutase, vimentin, malate dehydrogenase, and lamin
      B2. CONCLUSION(S): These biomarkers could help improve our understanding of the
      links between PCOS and OC and could potentially be used to identify subgroups of
      women with PCOS at increased risk of OC. More studies are required to further
      evaluate the role these biomarkers play in women with PCOS and OC.

PMID- 22959459
TI  - Dyspareunia and sexual dysfunction in women seeking fertility treatment.
AB  - OBJECTIVE: To compare rates of dyspareunia in infertile women and healthy
      controls. Secondary aims are to determine whether demographic characteristics,
      rates of sexual dysfunction, and baseline depression status differ between the
      two groups. DESIGN: A case-control study. SETTING: University-based faculty
      fertility and OB/GYN generalist clinics. PATIENT(S): Seventy-five infertile
      female subjects presenting to the infertility clinic and 210 women presenting to
      the generalist clinic for their annual exam. INTERVENTION(S): Completion of an
      anonymous survey including demographic information, the Female Sexual Function
      Index (FSFI), Patient-Health Questionnaire-9 (PHQ-9), and original questions
      regarding sexual pain. MAIN OUTCOME MEASURE(S): Rate of dyspareunia and sexual
      dysfunction. RESULT(S): There were no significant differences in rates of
      dyspareunia (37.6% controls vs. 30.7% study) or the rate of sexual dysfunction
      (31.9% controls vs. 37.3% study). Infertile women had more frequent intercourse
      than controls and were more likely to be married. There were otherwise no
      differences in baseline rates of depression, demographic characteristics, or
      individual domain scores of the FSFI. CONCLUSION(S): Women seeking fertility
      treatment had similar rates of dyspareunia and sexual dysfunction compared with
      controls.

PMID- 22959460
TI  - Low concentration of circulating antimullerian hormone is not predictive of
      reduced fecundability in young healthy women: a prospective cohort study.
AB  - OBJECTIVE: To evaluate whether circulating levels of antimullerian hormone (AMH)
      predict fecundability in young healthy women. DESIGN: Prospective cohort study.
      SETTING: General community. PATIENT(S): A total of 186 couples who intended to
      discontinue contraception to become pregnant were followed until pregnancy or for
      six menstrual cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Fecundability was evaluated by the monthly probability of conceiving (i.e.,
      fecundability ratio [FR]). In addition, circulating levels of LH, FSH, T, and sex
      hormone-binding globulin (SHBG) were evaluated in 158 of 186 women. RESULT(S):
      Fifty-nine percent of couples conceived during the study period. Compared to the
      reference group of women with medium AMH (AMH quintiles 2-4), fecundability did
      not differ significantly in women with low AMH (AMH quintile 1) (FR 0.81; 95%
      confidence interval [CI] 0.44-1.40). In contrast, women with high AMH (AMH
      quintile 5) had reduced fecundability (FR 0.62; 95% CI 0.39-0.99) after
      adjustment for covariates (woman's age, body mass index [BMI], smoking, diseases
      affecting fecundability, and oligozoospermia). Irregular menstrual cycles were
      more prevalent in women with high AMH compared with women with low or medium AMH
      levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and
      LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women
      with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and
      elevated LH:FSH ratio (2.4 vs. 1.7). CONCLUSION(S): Low AMH in healthy women in
      their mid-20s did not predict reduced fecundability. Even after exclusion of
      women with irregular cycles, the probability of conceiving was reduced in women
      with high AMH.

PMID- 22959461
TI  - Clinical factors associated with live birth after single embryo transfer.
AB  - OBJECTIVE: To identify patient, cycle, and retrieval characteristics associated
      with embryo implantation and live birth in patients undergoing single embryo
      transfer (SET). DESIGN: Analysis of prospectively collected IVF database.
      SETTING: Academic IVF program. PATIENT(S): All patient cycles meeting criteria
      for SET between June 2004 and September 2010. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy and live birth. RESULT(S): Single embryo transfer
      was performed in 438 cycles, resulting in a clinical pregnancy rate of 76.2% and
      a live birth rate of 66.8% per transfer. Clinical pregnancy was associated with
      younger female age, >= 58% mature (metaphase II) oocytes at the time of
      retrieval, and increasing blastocyst expansion. Ongoing pregnancy was associated
      with younger female age and more advanced blastocysts. A diagnosis of uterine
      factor was negatively associated with live birth. CONCLUSION(S): Even in a
      favorable prognosis population, younger female age is associated with clinical
      pregnancy and live birth. Although all patients underwent blastocyst transfer,
      expanded and hatching blastocysts were strongly associated with pregnancy and
      live birth. A diagnosis of uterine factor was the only infertility diagnosis
      found to affect live birth after SET. Obesity did not negatively affect SET
      outcome. These findings may assist physicians in determining the best candidates
      for SET.

PMID- 22959462
TI  - A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic
      programmed alteration in offspring rats of IUGR induced by prenatal caffeine
      ingestion.
AB  - Caffeine is a definite factor of intrauterine growth retardation (IUGR).
      Previously, we have confirmed that prenatal caffeine ingestion inhibits the
      development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose
      and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a
      programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested
      offspring rats. The results showed that prenatal caffeine (120 mg/kg.day)
      ingestion caused low body weight and high IUGR rate of pups; the concentrations
      of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group
      were significantly increased in the early postnatal period followed by falling in
      late stage; the level of blood glucose was unchanged, while blood total
      cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After
      chronic stress, the concentrations and the gain rates of blood ACTH and
      corticosterone were obviously increased, meanwhile, the blood glucose increased
      while the TCH and TG decreased in caffeine group. Further, the hippocampal
      mineralocorticoid receptor (MR) expression in caffeine group was initially
      decreased and subsequently increased after birth. After chronic stress, the
      11beta-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well
      as the MR/GR ratio were all significantly decreased. These results suggested that
      prenatal caffeine ingestion induced the dysfunction of HPA axis and associated
      neuroendocrine metabolic programmed alteration in IUGR offspring rats, which
      might be related with the functional injury of hippocampus. These observations
      provide a valuable experimental basis for explaining the susceptibility of IUGR
      offspring to metabolic syndrome and associated diseases.

PMID- 22959463
TI  - Arsenite-induced autophagy is associated with proteotoxicity in human
      lymphoblastoid cells.
AB  - Epidemiological studies of arsenic-exposed populations have provided evidence
      that arsenic exposure in humans is associated with immunosuppression. Previously,
      we have reported that arsenite-induced toxicity is associated with the induction
      of autophagy in human lymphoblastoid cell lines (LCL). Autophagy is a cellular
      process that functions in the degradation of damaged cellular components,
      including protein aggregates formed by misfolded or damaged proteins.
      Accumulation of misfolded or damaged proteins in the endoplasmic reticulum (ER)
      lumen causes ER stress and activates the unfolded protein response (UPR). In an
      effort to investigate the mechanism of autophagy induction by arsenite in the LCL
      model, we examined the potential contribution of ER stress and activation of the
      UPR. LCL exposed to sodium arsenite for 8-days induced expression of UPR
      activated genes, including CHOP and GRP78, at the RNA and the protein level.
      Evidence for activation of the three arms of the UPR was observed. The arsenite
      induced activation of the UPR was associated with an accumulation of protein
      aggregates containing p62 and LC3, proteins with established roles in the
      sequestration and autophagic clearance of protein aggregates. Taken together,
      these data provide evidence that arsenite-induced autophagy is associated with
      the generation of ER stress, activation of the UPR, and formation of protein
      aggregates that may be targeted to the lysosome for degradation.

PMID- 22959464
TI  - Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice
      exposed to perfluorooctane sulfonate (PFOS).
AB  - Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found
      in human and wildlife tissues. It has been reported that PFOS can cause atrophy
      of the immune organs and apoptosis of immunocytes in rodents. However, the
      mechanism behind such cause is still unclear. To understand the model of cell
      death and its mechanism on lymphoid cells in vivo, we conducted a dose/response
      experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were
      dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333mg/kg/day,
      yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50mg PFOS/kg,
      respectively, over 60days. The results showed that spleen and thymus weight were
      significantly reduced in the highest PFOS-dose-group (TAD 50mg PFOS/kg) compared
      to the control group, whereas liver weight was significantly increased. We
      analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by
      flow cytometry, and observed that both the percentage of apoptosis and the
      expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes
      increased in a dose-related manner after PFOS treatment. We also observed that
      PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl
      down regulation without changing the Bcl-2 and Bax expression. The down
      regulation of Bcl-xl was strongly indicating mitochondrial involvement in
      apoptosis. It is confirmed by the release of cytochrome c and activation of
      caspase-3. All of these findings establish an important role of p53 and
      mitochondrial function in PFOS induced toxic environment in the host.

PMID- 22959466
TI  - The antimicrobial and osteoinductive properties of silver nanoparticle/poly (DL
      lactic-co-glycolic acid)-coated stainless steel.
AB  - Implant-associated bacterial infections are one of the most serious complications
      in orthopedic surgery. Treatment of these infections often requires multiple
      operations, device removal, long-term systemic antibiotics, and extended
      rehabilitation, and is frequently ineffective, leading to worse clinical outcomes
      and increased financial costs. In this study, we evaluated silver
      nanoparticle/poly(DL-lactic-co-glycolic acid) (PLGA)-coated stainless steel
      alloy(SNPSA) as a potential antimicrobial implant material. We found that SNPSA
      exhibited strong antibacterial activity in vitro and ex vivo, and promoted MC3T3
      E1 pre-osteoblasts proliferation and maturation in vitro. Furthermore, SNPSA
      implants induced osteogenesis while suppressing bacterial survival in
      contaminated rat femoral canals. Our results indicate that SNPSA has simultaneous
      antimicrobial and osteoinductive properties that make it a promising therapeutic
      material in orthopedic surgery.

PMID- 22959465
TI  - Sustained protection against photoreceptor degeneration in tubby mice by
      intravitreal injection of nanoceria.
AB  - We previously reported that nanoceria can slow retinal degeneration in the tubby
      mouse for two weeks by multiple systemic injections. However, the long-term
      protection of retinal structure and function by directly deliver of nanoceria to
      the eye had not been explored. In this study, 172 ng of nanoceria in 1 MUl saline
      (1 mm) were intravitreally injected into tubby P7 pups and assays were performed
      at P28, P49, P80 and P120. The expression of antioxidant associated genes and
      photoreceptor-specific genes was significantly up regulated, the mislocalization
      of rod and cone opsins was decreased, and retinal structure and function were
      protected. These findings demonstrate that nanoceria can function as catalytic
      antioxidants in vivo and may be broad spectrum therapeutic agents for multiple
      types of ocular diseases.

PMID- 22959467
TI  - Signet ring cell carcinoma as a potential confounding factor in the analysis of
      outcomes with colorectal mucinous adenocarcinoma.

PMID- 22959468
TI  - Evaluation of sexuality, health-related quality-of-life and depression in
      advanced cancer patients: a prospective study in a Phase I clinical trial unit of
      predominantly targeted anticancer drugs.
AB  - BACKGROUND: The advent of molecular targeted agents (MTA) has opened a new era of
      therapy in oncology. However, some of the toxicities and side-effects of these
      new drugs are not explored as is the case with the potential impact of MTA on
      sexuality. This study aimed to prospectively evaluate health-related quality of
      life (HRQoL), depression and sexual function in advanced cancer patients treated
      in a Phase I drug unit evaluating MTA. PATIENTS AND METHODS: [corrected] In
      total, 63 of 74 eligible patients agreed to participate in the study. Four
      validated self-questionnaires were used: the Medical Outcomes Study Short-Form
      General Health Survey (SF12), the short form Beck Depression Inventory (BDI), the
      International Index of Erectile Function (IIEF) and the Female Sexual Function
      Index (FSFI). Forty-seven patients (75%) responded at baseline and 31 (65%) at 1
      month. RESULTS: This is the first evaluation of HRQoL, depression and sexual
      function in a Phase I drug unit. At baseline, patients had a good mental and
      physical function despite their disease progression. The response rate was 75%
      for sexual questionnaires. For 57% of females and 68% of males, quality of sexual
      life was a subject of interest. After 1-month of treatment, sexual dysfunction
      included lack of lubrication and comfort in females and erectile dysfunction in
      males with a statistical association of anti-angiogenic inhibitors in males
      (p=0.04). CONCLUSIONS: Patients on MTA in Phase I clinical trials had a preserved
      mental and physical activity whereas their sexual activity declined in both
      sexes. The impact of MTA on HRQoL and especially sexual function should be
      routinely assessed in further studies to better understand their potential impact
      in advanced cancer patients.

PMID- 22959469
TI  - Participation in adjuvant clinical breast cancer trials: does study participation
      improve survival compared to guideline adherent adjuvant treatment? A
      retrospective multi-centre cohort study of 9,433 patients.
AB  - Adjuvant clinical trials (CTs) usually compare a standard treatment regime versus
      an innovative new substance or regimen. Participation in CT however, is available
      for only few patients and exclusion criteria are usually very strict. Therefore
      we used an unselected patient cohort to investigate the following questions:
      MATERIAL AND METHODS: This German retrospective multi-centre cohort study
      included 9433 patients with primary breast cancer recruited from 1992 to 2008.
      RESULTS: One thousand two hundred and fifty-five (13.3%) patients participated in
      adjuvant clinical trials (PA) and 8178 (86.7%) did not (NPA). RFS was higher
      among participants (PA) than among non-participants (NPA) [p=0.006], but
      differences in overall survival (OAS) were not significant [p=0.15]. When
      stratified for guideline adherence, the outcome was not different for guideline
      conform NPA [RFS: p=0.88] [OAS: p=0.37] compared to PA. Survival parameters
      however, were significantly poorer in non-guideline conform PA [RFS: p<0.001]
      [OAS: p<0.001] and non-guideline conform NPA [RFS: p<0.001] [OAS: p<0.001] as
      compared to guideline adherent PA. DISCUSSION: There is a strong association
      between guideline adherence in adjuvant treatment in BC and survival. PA in
      clinical trials tended to higher survival rates, but only if guideline-adherent
      treatment was applied. Patients who do not have access to clinical trials may
      profit substantially from guideline-adherent adjuvant treatment.

PMID- 22959470
TI  - Developing a center for nursing research: an influence on nursing education and
      research through mentorship.
AB  - Nursing research, education, and mentoring are effective strategies to enhance
      and generate nursing knowledge. In order to explore new opportunities using an
      international and interdisciplinary approach, a Center for Nursing Research (CNR)
      was developed at Kean University a public institution for higher education in the
      United States. At the CNR, nursing professionals and students collaborate in all
      aspects of nursing education and the research process from a global perspective
      and across disciplines. The advancement of knowledge and understanding is of
      absolute importance to the field of nursing and other collaborative fields. The
      CNR functions to educate nursing faculty and students through scholarly
      activities with an ongoing commitment to nursing education and research.
      Mentorship in nursing education and research fosters professional, scholarly, and
      personal growth for both the mentor and mentee. The CNR serves as a model vehicle
      of applied, functional mentoring strategies and provides the venue to allow the
      mentor and mentee to collaborate in all aspects of nursing education and
      research.

PMID- 22959471
TI  - Transanal protrusion of gastric band tubing: a rare complication of laparoscopic
      adjustable gastric banding.

PMID- 22959472
TI  - Inflammation, obesity, and the promise of immunotherapy for metabolic disease.

PMID- 22959473
TI  - Comment on: Factor structure and predictive utility of the Binge Eating Scale in
      bariatric surgery candidate.

PMID- 22959474
TI  - Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age
      at diagnosis.
AB  - BACKGROUND: The peak incidence of Ewing sarcoma (EWS) is in adolescence, with
      little known about patients who are >=40 years at diagnosis. We describe the
      clinical characteristics and survival of this rare group. METHODS: This
      retrospective cohort study utilized the Surveillance Epidemiology and End Results
      database. 2780 patients were identified; including 383 patients diagnosed >=40
      years. Patient characteristics between age groups were compared using chi-squared
      tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods,
      compared with log-rank tests, and modeled using multivariable Cox methods. A
      competing risks analysis was performed to evaluate death due to cancer. RESULTS:
      Patients >=40 years of age were more likely to have extra-skeletal tumors (66.1%
      vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic
      disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients.
      Five-year survival for those age >=40 and age <40 were 40.6% and 54.3%,
      respectively (p < 0.0001). A Cox multivariable model controlling for differences
      between groups confirmed inferior survival for older patients (hazard ratio for
      death of 2.04; 95% CI 1.63-2.54; p < 0.0001); though treatment data were
      unavailable and not controlled for in the model. A competing risks analysis
      confirmed increased risk of cancer-related death in older patients. CONCLUSION:
      Patients >=40 years at diagnosis with EWS are more likely to have extra-skeletal
      tumors, metastatic disease, and axial primary tumors suggesting a difference in
      tumor biology. Independent of differences in these characteristics, older
      patients also have a lower survival rate.

PMID- 22959475
TI  - Combined application of energy and material flow analysis and ecological
      footprint for the environmental evaluation of a tailoring factory.
AB  - Two environmental evaluation methodologies, namely energy and materials flow
      analysis (EMFA) and ecological footprint (EF), were combined to assess a
      tailoring factory that produced jackets in the period 2002-2005. During the EMFA,
      aided by the software Umberto((r)) 5.5, cutting was identified as the most energy
      consuming stage and gas-oil as an important source of pollution in spite of its
      low contribution to energy supply. The EF appraisal was built on the basis of a
      previous work, incorporating methodological contributions developed by the
      authors that made the indicator more suitable for its application at corporate
      level. Initially, an increasing tendency in the indicator was observed (from 37.8
      in 2002 to 45.2 gm(2)/jacket in 2005). When including other emissions apart from
      CO(2), the results conveyed a significant increase in EF that ranged from 80% in
      2002 to 14% in 2004, demonstrating that this contribution should not be
      disregarded when evaluating production processes. Finally, sensitivity analyses
      were carried out to assess the influence in the EF of the variability in input
      variables. When emissions were not included, the most influencing input flow was
      the cotton fabric; otherwise gas-oil became the most relevant factor. Therefore,
      its substitution for cleaner sources of energy was advised.

PMID- 22959476
TI  - Copper recovery from ore by liquid-liquid extraction using aqueous two-phase
      system.
AB  - We investigated the extraction behavior of Cu(II) in the aqueous two-phase system
      (ATPS) formed by (L35+MgSO(4)+H(2)O) or (L35+(NH(4))(2)SO(4)+H(2)O) in the
      presence of the extracting agent 1-(2-pyridylazo)-2-naphthol (PAN). At pH=3 and a
      PAN concentration of 0.285 mmol kg(-1), both ATPS lead to the effective
      separation of Cu(II) from other metallic ions (Zn(II), Co(II), Ni(II) and
      Fe(III)). High separation factors range between 1000 and 10,000 were obtained for
      the extraction of Cu(II) and concomitant metallic ions. This ATPS was used for
      the extraction of Cu(II) from a leached ore concentrate with a extraction
      percentage of 90.4 +/- 1.1%; other metals were mainly located in the bottom
      phase.

PMID- 22959477
TI  - Highly dispersed Co0.5Zn0.5Fe2O4/polypyrrole nanocomposites for cost-effective,
      high-performance defluoridation using a magnetically controllable microdevice.
AB  - Highly dispersed Co(0.5)Zn(0.5)Fe(2)O(4)/polypyrrole (CZFO/PPy) nanocomposites
      with enhanced electromagnetic properties and large surface area were rapidly and
      controllably prepared using microfluidic reactors. A novel magnetically
      controllable microdevice using the new adsorbent in a highly dispersed form was
      assembled and used for fluoride adsorption. Compared with traditional adsorption
      methods, the device displayed high adsorption efficiency and capacity. The
      adsorbents were regenerated with no significant loss in defluoridation ability,
      which indicates that the device is a realistic and highly efficient alternative
      way of removing fluoride pollution at low cost.

PMID- 22959479
TI  - Fractures in hospitalized children.
AB  - Hospitalized children have multiple risk factors for fragility fractures, related
      to disease pathophysiology, treatments, nutritional status and immobilization.
      Recognition and treatment of these risk factors are important to prevent
      morbidity associated with fractures and to promote current and future bone
      health. Many knowledge gaps remain regarding the ideal nutrition, physical
      activity, and medication regimens needed to optimize bone health and reduce the
      risk of fractures over the life course. This article reviews the pathogenesis,
      risk factors, treatment and prevention strategies for fractures in hospitalized
      infants and children.

PMID- 22959478
TI  - Rapamycin does not affect post-absorptive protein metabolism in human skeletal
      muscle.
AB  - Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase
      in skeletal muscle protein synthesis in response to resistance exercise or amino
      acid ingestion. OBJECTIVE: To determine whether rapamycin administration
      influences basal post-absorptive protein synthesis or breakdown in human skeletal
      muscle. MATERIALS/METHODS: Six young (26+/-2 years) subjects were studied during
      two separate trials, in which each trial was divided into two consecutive 2 h
      basal periods. The trials were identical except during one trial a single oral
      dose (16 mg) of rapamycin was administered immediately prior to the second basal
      period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h
      to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I
      and LC3B-II protein) associated with each 2 h basal period. RESULTS: During the
      Control trial, muscle protein synthesis, whole body protein breakdown
      (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar
      between both basal periods (p>0.05). During the Rapamycin trial, these variables
      were similar to the Control trial (p>0.05) and were unaltered by rapamycin
      administration (p>0.05). Thus, post-absorptive muscle protein metabolism and
      mTORC1 signaling were not affected by rapamycin administration. CONCLUSIONS:
      Short-term rapamycin administration may only impair protein synthesis in human
      skeletal muscle when combined with a stimulus such as resistance exercise or
      increased amino acid availability.

PMID- 22959480
TI  - A response to Edzi (AIDS): Malawi faith-based organizations' impact on HIV
      prevention and care.
AB  - African faith-based organization (FBO) leaders influence their members' HIV
      knowledge, beliefs, and practices, but their roles in HIV prevention and care are
      poorly understood. This article expands the work of Garner (2000) to test the
      impact of FBO influence on member risk and care behaviors, embedding it in the
      Theory of Planned Behavior. Qualitative interviews and quantitative surveys were
      collected from five FBOs (Christian and Muslim) in Malawi and analyzed using
      mixed methods. Contrary to Garner, we found that the level of power and influence
      of the FBO had no significant impact on the risk-taking behaviors of members;
      however, leaders' HIV knowledge predicted members' behaviors. Stigmatizing
      attitudes of leaders significantly decreased members' care behaviors, but FBO
      hierarchy tended to increase members' care behaviors. The power of local church
      and mosque leaders to influence behavior could be exploited more effectively by
      nurses by providing support, knowledge, and encouragement to churches and
      mosques.

PMID- 22959481
TI  - Exploratory study: evaluating the effects of fish oil and controlled diet to
      reduce triglyceride levels in HIV.

PMID- 22959482
TI  - Reduction of infectious bursal disease virus replication by shRNAs targeting the
      VP1 and VP2 genes driven by chicken U6 promoter.
AB  - Infectious bursal disease virus (IBDV) causes a highly contagious and
      immunosuppressive disease in young chickens and results in considerable economic
      losses for the poultry industry. To suppress the replication of IBDV, two short
      hairpin RNAs (shRNAs) were designed for targeting the VP1 and VP2 genes of IBDV.
      Recombinant plasmids carrying each shRNA or two shRNAs were constructed based on
      vector pSilencer2.1-U6 in which the human U6 promoter was replaced with chicken
      U6 promoter. In chicken embryo fibroblasts, transfection with these shRNA
      plasmids 24h before infection with IBDV B87 reduced 50% tissue culture infectious
      doses (TCID(50)) from 10(8.75) TCID(50)/0.1 mL to 10(3.75)-10(1.0) TCID(50)/0.1
      mL. In 10-day old specific pathogen-free (SPF) chicken embryos, incubation with a
      mixture of IBDV B87 and a shRNA plasmid via the allantoic cavity resulted in 100%
      mortality and high IBDV virus titer in the control group but 25-0% mortality and
      near normal embryo development in the specific shRNA groups; additionally, IBDV
      VP1 and VP2 mRNA levels were reduced by 72-95% in the shRNA groups as compared
      with the control groups. When challenged with a virulent strain IBDV GX8/99, 14
      day-old chickens pre-treated with the single shRNA plasmids or the dual shRNA
      plasmid showed approximately 70% or 90% survival at 5 days post-challenge while
      those pre-treated with control plasmid or saline had less than 5% survival. The
      current study suggests that two IBDV shRNAs expressed by a plasmid under chicken
      U6 promoter could effectively and synergistically reduce IBDV replication in
      vitro and in vivo.

PMID- 22959483
TI  - Dealing with chronic disease - the role of structured programmes and guidelines.

PMID- 22959484
TI  - Local heart irradiation of ApoE(-/-) mice induces microvascular and endocardial
      damage and accelerates coronary atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Radiotherapy of thoracic and chest-wall tumors increases
      the long-term risk of radiation-induced heart disease, like a myocardial infarct.
      Cancer patients commonly have additional risk factors for cardiovascular disease,
      such as hypercholesterolemia. The goal of this study is to define the interaction
      of irradiation with such cardiovascular risk factors in radiation-induced damage
      to the heart and coronary arteries. MATERIAL AND METHODS: Hypercholesterolemic
      and atherosclerosis-prone ApoE(-/-) mice received local heart irradiation with a
      single dose of 0, 2, 8 or 16 Gy. Histopathological changes, microvascular damage
      and functional alterations were assessed after 20 and 40 weeks. RESULTS:
      Inflammatory cells were significantly increased in the left ventricular
      myocardium at 20 and 40 weeks after 8 and 16 Gy. Microvascular density decreased
      at both follow-up time-points after 8 and 16 Gy. Remaining vessels had decreased
      alkaline phosphatase activity (2-16 Gy) and increased von Willebrand Factor
      expression (16 Gy), indicative of endothelial cell damage. The endocardium was
      extensively damaged after 16 Gy, with foam cell accumulations at 20 weeks, and
      fibrosis and protein leakage at 40 weeks. Despite an accelerated coronary
      atherosclerotic lesion development at 20 weeks after 16 Gy, gated SPECT and
      ultrasound measurements showed only minor changes in functional cardiac
      parameters at 20 weeks. CONCLUSIONS: The combination of hypercholesterolemia and
      local cardiac irradiation induced an inflammatory response, microvascular and
      endocardial damage, and accelerated the development of coronary atherosclerosis.
      Despite these pronounced effects, cardiac function of ApoE(-/-) mice was
      maintained.

PMID- 22959485
TI  - Psychopathy and the prediction of alcohol-related physical aggression: the roles
      of impulsive antisociality and fearless dominance.
AB  - BACKGROUND: It is well established that individual difference factors modulate
      aggression under the acute effects of alcohol. In this investigation, we tested
      the hypothesis that one core dimension of psychopathy, Impulsive Antisociality,
      would modulate intoxicated aggression, whereas another dimension, Fearless
      Dominance, would not. METHODS: Participants were 516 young social drinkers (253
      men and 263 women). Psychopathy was measured using the Psychopathic Personality
      Inventory (PPI; Lilienfeld and Andrews, 1996). Following the consumption of
      either an alcohol or a placebo beverage, aggression was measured with a task in
      which participants administered and received electric shocks to/from a fictitious
      opponent under the guise of a competitive reaction-time task. RESULTS:
      Hierarchical regression analyses supported our hypothesis: Impulsive
      Antisociality predicted aggression under alcohol, whereas Fearless Dominance did
      not. CONCLUSIONS: Persons who tend to endorse antisocial and impulsive
      externalizing behaviors appear to be at greater risk for aggression under the
      acute influence of alcohol.

PMID- 22959486
TI  - Oestrous cycle-related changes in production of Toll-like receptors and
      prostaglandins in the canine endometrium.
AB  - The objectives of this study were to evaluate the following events in the canine
      endometrium over the course of the oestrous cycle: (i) the transcriptional
      profiles of genes encoding the Toll-like receptors (TLR1-TLR7 and TLR9); (ii) the
      transcription and protein expression levels of TLR2 and TLR4; (iii) the gene
      transcription profile of prostaglandin synthesis enzymes (PTGS2, PGES and PGFS);
      (iv) the response pattern of PGF(2alpha) and PGE(2) following exposure of
      endometrial explants to LPS and LTA. TLR1-TLR7 and TLR9 genes were transcribed in
      the endometrium of bitches throughout the oestrous cycle, which indicates that
      TLR-mediated immune surveillance is an important component of the defence
      mechanisms within the uterus. Canine endometrial mRNA and protein expression of
      TLR2 and TLR4 was up-regulated at the late dioestrus and anoestrus and was the
      lowest in the follicular phase and early dioestrus. The decreased mRNA and
      protein levels observed at early dioestrus may favour implantation, but may also
      be linked to the high prevalence of pyometra at this stage of the oestrous cycle.
      After LPS and LTA stimulation, endometrial explants produced more PGF(2alpha)
      than PGE(2), which may be related to the early demise of the corpus luteum
      observed in vivo in canine pyometra cases. Overall, these results indicate that
      TLRs are involved in the activation of the inflammatory response associated with
      pyometra in the bitch. TLRs may therefore be therapeutic targets for the control
      of uterine bacterial infections in the bitch and potentially in other species.

PMID- 22959487
TI  - Exercise improves physical capacity in obese patients with schizophrenia: pilot
      study.

PMID- 22959488
TI  - Association between methylmercury and cardiovascular risk factors in a native
      population of Quebec (Canada): a retrospective evaluation.
AB  - BACKGROUND: Epidemiological evidence suggests a negative impact of methylmercury
      (MeHg) on cardiovascular risk factors such as blood pressure (BP) and heart rate
      (HR). This issue is of concern in Arctic populations such as in the Inuit of
      Nunavik since this contaminant is accumulated in fish and marine mammals, which
      still represent the subsistence diet of this population. OBJECTIVE: We examined
      the associations between MeHg and BP and resting HR among Inuit adults. METHODS:
      The "Sante Quebec" health survey was conducted in 1992 in the 14 villages of
      Nunavik and a complete set of data was obtained for 313 Inuit adults>=18 years.
      Blood samples were collected in order to determine total mercury, lead, total
      polychlorinated biphenyls (PCBs), n-3 polyunsaturated fatty acids (PUFAs),
      fasting glucose and lipid profile while socio-demographic variables were obtained
      through questionnaires. Anthropometric measurements as well as BP and resting HR
      were obtained using standardised protocols. Pulse pressure (PP: systolic BP minus
      diastolic BP) was also calculated. Multiple linear regression was used in order
      to determine the change in the dependent variables associated with the quartiles
      of MeHg concentration, taking the quartile 1 as reference. RESULTS: The mean age
      of the participants was 38+/-14 years and the sample was composed of 132 men
      (42.2%) and 181 women (57.8%). MeHg geometric mean was 15.4 MUg/L (95%CI: 13.9
      17.0) and levels ranged from 0.8 to 112.0 MUg/L. Resting HR increased linearly
      across quartiles of blood MeHg concentration after adjusting for confounders (p
      for trend=0.02). An increase of 6.9 beats per minute (bpm) between the 4th and
      1st quartile was observed after adjusting for confounders. No significant
      association was observed between blood MeHg and systolic BP, diastolic BP or PP.
      CONCLUSIONS: MeHg was associated with increasing resting HR after considering
      traditional risk factors as well as other contaminants (lead and total PCBs) and
      n-3 PUFAs. In contrast, no significant association with blood pressure was
      observed in this study.

PMID- 22959489
TI  - Archaeal and bacterial ammonia-oxidisers in soil: the quest for niche
      specialisation and differentiation.
AB  - Autotrophic archaeal and bacterial ammonia-oxidisers (AOA and AOB) drive soil
      nitrification. Ammonia limitation, mixotrophy, and pH have been suggested as
      factors providing niche specialisation and differentiation between soil AOA and
      AOB. However, current data from genomes, cultures, field studies, and microcosms
      suggest that no single factor discriminates between AOA and AOB. In addition,
      there appears to be sufficient physiological diversity within each group for
      growth and activity in all soils investigated, with the exception of acidic soils
      (pH <5.5), which are dominated by AOA. Future investigation of niche
      specialisation in ammonia-oxidisers, and other microbial communities, requires
      characterisation of a wider range of environmentally representative cultures,
      emphasis on experimental studies rather than surveys, and greater consideration
      of small-scale soil heterogeneity.

PMID- 22959490
TI  - [How I do... a transient uterine artery occlusion by laparoscopy].

PMID- 22959492
TI  - Laparoscopic adrenalectomy for adrenocortical carcinoma: a medico-surgical
      perspective.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor carrying a dismal
      prognosis. The only hope for cure is a complete surgical resection. Whether this
      can be achieved by laparoscopic adrenalectomy (LA) remains questionable, and is
      now a "hot topic" for the medical and surgical community. The aim of this article
      was to review the result of LA for ACC in the view of the recent and highly
      controversial literature. METHODS: Electronic searches in MEDLINE via PubMed
      regarding relevant English language studies published through February 2012 were
      reviewed. RESULTS: Initially, LA for ACC has only been reported as case report or
      short series. This initial experience emphasized the potential deleterious effect
      of LA, especially in case of tumor spillage during the procedure. Recently,
      larger studies comparing laparoscopic and open approach for ACC have been
      published. These retrospective studies reported conflicting results, either
      equivalent results or an increased risk of tumor spillage and peritoneal
      carcinomatosis, and are all limited by several bias. CONCLUSION: Overall, no
      definitive answer regarding the equivalence of LA for ACC can be drawn from the
      available literature. Even if it is likely that for well-selected cases the same
      procedure performed by laparoscopic or open approach may provide equivalent
      results, we believe that in face of a modest benefit, the risk of tumor spillage
      during LA should be an important consideration. Even if it is tenting,
      laparoscopic approach for ACC should be avoided, at least until a clear standard
      of surgical care has been achieved and established for the open approach.

PMID- 22959491
TI  - Clinical assessment of oral dryness: development of a scoring system related to
      salivary flow and mucosal wetness.
AB  - OBJECTIVE: The aim of this study was to develop a clinical oral dryness score
      (CODS) for routine use in assessment of xerostomia patients and determine its
      relationship with salivary flow rates and mucosal wetness. STUDY DESIGN: CODS was
      determined from 10 features of oral dryness, each scoring as 1 point for a total
      score of 0-10. CODS, salivary flow rates, and mucosal wetness were measured in
      100 patients and 50 healthy control subjects. The reproducibility of CODS was
      0.89-0.96 (intraclass correlation coefficient). RESULTS: The mean +/- SD CODS in
      patients was 6.0 +/- 1.6 compared with 1.0 +/- 0.9 for control subjects (P <
      .001), and the highest mean value was in the primary Sjogren syndrome group.
      There was a general inverse relationship in patients between mean CODS and
      salivary flow rate (P < .01) and mean CODS and mucosal wetness (P < .01).
      CONCLUSIONS: The CODS was found to be useful, easy to use, and reliable for
      routine assessment of the severity of dry mouth.

PMID- 22959493
TI  - [Diabetes and Ramadan].
AB  - Ramadan, one of the five pillars of Islam, is a holy month for Muslims. During
      this month, they have a duty to fast every day from sunrise to sunset. This
      religion spares diabetics and persons with chronic illnesses from this duty,
      because lack of eating and drinking all the day has many bad consequences on
      their health. But, because of a very strong habit, by solidarity with the family,
      or by fear of exclusion from the society, many diabetics insist on fasting as
      demonstrated by numerous studies. The problem is, when they fast, diabetics are
      at risk from complications such as severe hypoglycemia, hyperglycemia,
      ketoacidosis, dehydration and thrombosis. To avoid this, consensus and
      recommendations have emerged in order to develop new approaches that would
      minimize the various complications. It appears from different recommendations
      that only diabetics whose equilibrium is stable, free of degenerative
      complications, and able to manage properly their diseases will be allowed to
      fast. The physician's role is to assist the faithful person to Ramadan by raising
      awareness of lifestyle and dietary rules, daily self-monitoring, and a new
      adjustment of treatment.

PMID- 22959494
TI  - Sleep disordered breathing and other sleep dysfunction in myotonic dystrophy type
      2.

PMID- 22959495
TI  - Mechano-regulation of the beating heart at the cellular level--mechanosensitive
      channels in normal and diseased heart.
AB  - The heart as a contractile hollow organ finely tunes mechanical parameters such
      as stroke volume, stroke pressure and cardiac output according to filling
      volumes, filling pressures via intrinsic and neuronal routes. At the cellular
      level, cardiomyocytes in beating hearts are exposed to large mechanical stress
      during successive heart beats. Although the mechanisms of excitation-contraction
      coupling are well established in mammalian heart cells, the putative contribution
      of mechanosensitive channels to Ca2+ homeostasis, Ca2+ signaling and force
      generation has been primarily investigated in relation to heart disease states.
      For instance, transient receptor potential channels (TRPs) are up-regulated in
      animal models of congestive heart failure or hypertension models and seem to play
      a vital role in pathological Ca2+ overload to cardiomyocytes, thus aggravating
      the pathology of disease at the cellular level. Apart from that, the contribution
      of mechanosensitive channels (MsC) in the normal beating heart to the downstream
      force activation cascade has not been addressed. We present an overview of the
      current literature and concepts of mechanosensitive channel involvement in
      failing hearts and cardiomyopathies and novel data showing a likely contribution
      of Ca2+ influx via mechanosensitive channels in beating normal cardiomyocytes
      during systolic shortening.

PMID- 22959496
TI  - Clinical outcomes after repair of quadriceps tendon rupture: a systematic review.
AB  - The existing evidence regarding the management of quadriceps tendon rupture
      remains obscure. The aim of the current review is to investigate the
      characteristics, the different techniques employed and to analyse the clinical
      outcomes following surgical repair of quadriceps tendon rupture. An Internet
      based search of the English literature of the last 25 years was carried out. Case
      reports and non-clinical studies were excluded. The methodological quality of the
      included studies was assessed using the Coleman Methodology Score. All data
      regarding mechanism and site of rupture, type of treatment, time elapsed between
      diagnosis and repair, patients' satisfaction, clinical outcome, return to pre
      injury activities, complications and recurrence rates were extracted and
      analysed. Out of 474 studies identified, 12 met the inclusion criteria. The
      average of Coleman Methodology Score was 50.46/100. In total 319 patients were
      analysed with a mean age of 57 years (16-85). The mean time of follow-up was 47.5
      months (3 months to 24 years). The most common mechanism of injury was simple
      fall (61.5%). Spontaneous ruptures were reported in 3.2% of cases. The most
      common sites of tear were noted between 1cm and 2 cm of the superior pole of the
      patella and, in the older people, at the osseotendinous junction. The most
      frequently used repair technique was patella drill holes (50% of patients).
      Simple sutures were used in mid-substance ruptures. Several reinforcement
      techniques were employed in case of poor quality or retraction of the torn ends
      of tendon. The affected limb was immobilised in a cast for a period of 3-10
      weeks. Quadriceps muscular atrophy and muscle strength deficit were present in
      most of the cases. Worst results were noted in delayed repairs. Reported
      complications included heterotopic ossifications in 6.9% of patients, deep venous
      thrombosis or pulmonary embolism in 2.5%, superficial infection in 1.2% and deep
      infection in 1.1%. It appears that the type of surgical repair does not influence
      the clinical results. The majority of the studies reported good or excellent ROM
      and return to the pre-injury activities. The overall rate of re-rupture was 2%.

PMID- 22959498
TI  - Recapitulation of four hypertension susceptibility genes (CSK, CYP17A1, MTHFR,
      and FGF5) in East Asians.
AB  - OBJECTIVE: A recent genome wide association study identified eight hypertension
      susceptibility loci in Europeans. Subsequently, several studies have investigated
      these associations in East Asian populations. The results of these studies,
      however, have been inconsistent. A meta-analysis was performed to assess the
      associations of the most published polymorphisms, including CSK rs1378942,
      CYP17A1 rs11191548, MTHFR rs17367504, and FGF5 rs16998073 polymorphisms with
      hypertension. METHODS: Published literature from PubMed and Embase databases was
      retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were
      calculated using fixed- or random-effects model. RESULTS: Seven studies (16,368
      cases /19,707 controls) for CSK rs1378942 polymorphism, seven studies (15,688
      cases /18,784 controls) for CYP17A1 rs11191548 polymorphism, four studies (7994
      cases / 12,844 controls) for MTHFR rs17367504 polymorphism, and three studies
      (6026 cases / 8393 controls) for FGF5 rs16998073 polymorphism were included in
      the meta-analysis. The results suggested that both CYP17A1 rs11191548 and FGF5
      rs16998073 polymorphisms were significantly associated with hypertension risk in
      East Asians (CYP17A1 rs11191548 (random effect model): OR=1.16, 95% CI 1.07-1.25,
      p=3.59*10(-4), I(2)=78.2%, p (heterogeneity)=1.14*10(-4); FGF5 rs16998073 (random
      effect model): OR=1.30, 95% CI 1.23-1.37, p=6.29*10(-21), I(2)=65.0%, p
      (heterogeneity)=0.009); whereas no significant association was observed for CSK
      rs1378942 (fix effect model: OR=1.09, 95% CI 0.98-1.22, p=0.128, I(2)=0.0%, p
      (heterogeneity)=0.820), or MTHFR rs17367504 (fix effect model: OR=1.06, 95% CI
      0.98-1.14, p=0.126, I(2)=0.0%, p (heterogeneity)=0.822). CONCLUSION: The present
      meta-analysis indicated significant associations of both CYP17A1 rs11191548 and
      FGF5 rs16998073 polymorphisms with hypertension susceptibility in East Asians.

PMID- 22959497
TI  - Effect of low- and high-glycemic load on circulating incretins in a randomized
      clinical trial.
AB  - OBJECTIVE: Low-glycemic load diets lower post-prandial glucose and insulin
      responses; however, the effect of glycemic load on circulating incretin
      concentrations is unclear. We aimed to assess effects of dietary glycemic load on
      fasting and post-prandial glucose, insulin and incretin (i.e., glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1))
      concentrations and to examine for effect modification by adiposity. MATERIALS AND
      METHODS: We conducted a single-center, randomized controlled crossover feeding
      trial in which a subset of participants had post-prandial testing. Participants
      were recruited from the local Seattle area. We enrolled 89 overweight-obese (BMI
      28.0-39.9 kg/m(2)) and lean (BMI 18.5-25.0 kg/m(2)) healthy adults. Participants
      consumed two 28-day, weight-maintaining high- and low-glycemic load controlled
      diets in random order. Primary outcome measures were post-prandial circulating
      concentrations of glucose, insulin, GIP and GLP-1, following a test breakfast.
      RESULTS: Of the 80 participants completing both diet interventions, 16 had
      incretin testing and comprise the group for analyses. Following each 28-day high-
      and low-glycemic load diet, mean fasting concentrations of insulin, glucose, GIP
      and GLP-1 were not significantly different. Mean integrated post-prandial
      concentrations of glucose, insulin and GIP were higher (1504+/-476 mg/dL/min,
      p<0.01; 2012+/-644 MUU/mL/min, p<0.01 and 15517+/-4062 pg/mL/min, p<0.01,
      respectively) and GLP-1 was lower (-81.6+/-38.5 pmol/L/min, p<0.03) following the
      high-glycemic load breakfast as compared to the low-glycemic load breakfast. Body
      fat did not significantly modify the effect of glycemic load on metabolic
      outcomes. CONCLUSIONS: High-glycemic load diets in weight-maintained healthy
      individuals lead to higher post-prandial GIP and lower post-prandial GLP-1
      concentrations. Future studies evaluating dietary glycemic load manipulation of
      incretin effects would be helpful for establishing diabetes nutrition guidelines.

PMID- 22959499
TI  - Beneficial effects of 12 weeks of aerobic compared with resistance exercise
      training on perceived appetite in previously sedentary overweight and obese men.
AB  - OBJECTIVE: To investigate the effect of 12 weeks of aerobic (AER) compared with
      resistance training (RES) on perceived hunger and fullness, together with
      appetite-related hormones in both the fasted state and postprandially. METHODS:
      Thirty-three inactive, overweight and obese men (age 49+/-7 years; BMI 30.8+/-4.2
      kg/m(2)) were allocated to either AER exercise (n=12), RES exercise (n=13) or a
      control group (CON; n=8). AER and RES completed 12 weeks of training (3 sessions
      per week), while CON continued their sedentary routine. Perceived hunger and
      fullness, together with appetite-related hormones (active ghrelin, leptin,
      insulin, pancreatic polypeptide (PP), and peptide tyrosine tyrosine (PYY)) were
      assessed pre and post-intervention in the fasted state and in response to oral
      glucose consumption (1284 kJ; 75 g carbohydrate). RESULTS: Both AER and RES
      training elicited a decrease in fat mass (p<0.05), while CON did not. There was
      no difference in perceived hunger either in the fasted state (p>0.05) or in
      response to caloric consumption (p>0.05) following the intervention in any group.
      In contrast, both fasting and postprandial perceived fullness was higher
      following AER exercise (p<0.05), but not RES exercise or CON. These observations
      were not associated with alterations in fasting or postprandial active ghrelin,
      PP or PYY, although fasting and postprandial leptin was reduced following both
      AER and RES training (p<0.05). CONCLUSION: Aerobic exercise training is
      associated with an increase in satiety, while an equivalent period of resistance
      training is not.

PMID- 22959500
TI  - Efficacy of lifestyle interventions in reducing diabetes incidence in patients
      with impaired glucose tolerance: a systematic review of randomized controlled
      trials.
AB  - OBJECTIVE: Every year over 3.8 million people are dying of diabetes and its
      complications. Lifestyle intervention was suggested to have beneficial effects in
      preventing and reducing diabetes incidence. Interventions in patients with
      impaired glucose tolerance (IGT), who belong to a high risk group in developing
      diabetes, are supposed to be especially effective. According to the evidence
      hierarchy, a 1a level of evidence is missing and therefore a systematic review
      verifying the efficacy of lifestyle intervention is needed. MATERIALS/METHODS:
      Systematic review: The electronic database PubMed, Embase, Cochrane Central
      Register of Controlled Trials, Cochrane Database of Systematic Reviews, and
      Health Technology Assessment database were searched. Main inclusion criteria were
      randomized controlled trials, impaired glucose tolerance, lifestyle intervention
      with control group and observation time >6 months. Outcome measures were all
      diabetes events, as defined by the authors of each study, all-cause mortality,
      diabetes mortality, and quality adjusted life years (QALY). Two independent
      reviewers abstracted the studies by title, abstract and full-text analysis.
      Furthermore the reporting quality of each study was assessed by using the CONSORT
      criteria (Consolidated Standards of Reporting Trials) and the methodological
      quality by SIGN 50 instrument (Scottish Intercollegiate Guidelines Network
      methodology checklist for randomized controlled trials). The primary outcome
      measure was diabetes incidence. Secondary outcome measures were overall
      mortality, disease-specific mortality, quality adjusted life years (QALY), and
      clinical parameters; body mass index (BMI), weight change, blood pressure, blood
      parameter, smoking, alcohol consumption. RESULTS: 7 trials which included 25
      relevant publications were identified. Kappa Cohens for title-analysis were
      K=0.77, (CI=0.71-0.83), abstract-analysis K=0.81 (CI=0.64-0.92) and full-text
      analysis K=0.78 (CI=0.57-0.98). Overall 5663 patients were analyzed with primary
      follow-up time: India (3y), Japan (4y), Sweden (5y), Da Qing (6y), SIM (3y), DPP
      (5y), DPS (4y) and drop-out rate ranges from 5% to 28%. Diabetes incidence ranges
      from 3% to 46% in the intervention group and 9.3% to 67.7% in the control group.
      The India study reported ARR=16%, RRR=29% (p=0.018), Japan: ARR=6.3%, RRR=65%
      (p<0.001), Sweden: ARR=4%, RRR=25% (p=not significant), Da Qing: ARR=22%, RRR=32%
      (p<0.05), SLIM: ARR=20%, RRR=53% (p=0.025), DPP: ARR=15%, RRR=58% (significant,
      no p-value reported), and DPS: ARR=12%, RRR=52% (significant, no p-value
      reported). Mortality and morbidity were only analyzed in Da Qing study which
      showed no statistical differences (overall mortality: HRR 0.96, CI 0.65-1.41, CVD
      mortality: HRR 0.83; CI 0.48-1.40, CVD event: HRR 0.98; CI 0.71-1.37).
      CONCLUSION: Under consideration of heterogeneity in lifestyle interventions and
      follow up time of the included studies, this systematic review illustrated that
      lifestyle intervention can have a beneficial effect on the incidence of diabetes
      in patients with impaired glucose tolerance. However, several studies found the
      effect of lifestyle intervention decreased after intervention was terminated. No
      long-term benefit in mortality and morbidity was found. Development of
      standardized lifestyle intervention program is strongly needed and further long
      term intervention trials using this program are crucial in evidencing the long
      term efficacy.

PMID- 22959501
TI  - Shoulder arthrodesis with plate fixation: Functional outcome analysis.
AB  - Fifty-seven patients underwent shoulder arthrodesis with a single plate. The
      technique utilized included both glenohumeral and acromiohumeral arthrodesis. A
      10-hole plate was used for internal fixation. The position utilized was 30
      degrees  abduction, 30 degrees  internal rotation, and 30 degrees  flexion. Forty
      six patients underwent the procedure for brachial plexus injury, six patients for
      multidirectional shoulder instability, two patients for osteoarthritis, two
      patients for failed total shoulder arthroplasties, and one for infection. The
      patients were independently reviewed by a research clinician and their function
      assessed according to their ability to perform activities of daily living,
      subjective satisfaction with the procedure, and the degree of pain they felt in
      their shoulder. Fifty-four shoulders fused within 10 degrees  of the desired
      position. Three patients required secondary bone grafting. The complication rate
      was 14%. Patient satisfaction was highest in those patients undergoing the
      procedure for brachial plexus injury, osteoarthritis, and failed total shoulder
      arthroplasty (p = 0.0046). Four patients with multidirectional shoulder
      instability continued to complain of instability in spite of solid arthrodesis (p
      < 0.01). The difference in the cumulative activities of daily living score
      between the brachial plexus injury and poor hand function group and the
      multidirectional shoulder instability group and patients with other diagnoses was
      significant (p = 0.0001). Preoperative diagnosis, hand function, and work status
      were significant determinants of patient satisfaction and the cumulative
      activities of daily living score (p = 0.0001).

PMID- 22959502
TI  - Etiologic factors in isolated paralysis of the serratus anterior muscle: A report
      of 197 cases.
AB  - One hundred ninety-seven cases of isolated paralysis of the serratus anterior
      muscle were analyzed to discover common etiologic factors and the mechanisms of
      injury producing this disorder. Exertion preceded 69 (35%) of the cases, and
      trauma caused 51 (26%) of the cases. Twenty-two (11%) occurred after locally
      invasive procedures, 13 (7%) after infection, and 10 (5%) after anesthesia.
      Sleeping position or exposure to cold proved to be causes in a few cases. Twenty
      nine (15%) of the cases were of unknown cause. Evaluation of the mechanism of the
      injury indicated that in most cases the lesion was mechanical in origin. The data
      suggested that the long thoracic nerve is not unusually susceptible to infectious
      or toxic neuropathy, as has previously been supposed.

PMID- 22959503
TI  - The long thoracic nerve: Possible mechanisms of injury based on autopsy study.
AB  - Forty dissections in 21 adult cadavers were analyzed to determine whether the
      long thoracic nerve could be mechanically damaged or its blood supply threatened
      along its peripheral course. The mean length of the nerve was 21.9 cm measured
      from the upper border of the serratus anterior; it ended an average of 8.4 cm
      distal to the inferior angle of the scapula. Three postmortem arteriographs were
      done, and the blood supply to the lower part of the nerve was observed
      radiographically and in the dissections. The nerve and its blood supply were
      found to be vulnerable for both compression and stretching anterior to the lower
      part of the scapula. The findings differ from previous theory about nerve injury
      at the level of the second rib. Marked interindividual differences in the course
      of the nerve were noted; this may explain why some people experience paralysis
      while others do not.

PMID- 22959504
TI  - Humeral head replacement for acute, four-part proximal humerus fractures.
AB  - Twenty-eight patients with acute, four-part proximal humerus fractures and
      fracture dislocations were treated with humeral head replacement. At an average
      follow-up of 37 months (range 12 to 96 months) one author examined 24 patients
      and evaluated them according to the criteria of the American Shoulder and Elbow
      Surgeons. There were no infections. One patient had subsequent surgery for joint
      contracture. Nine (38%) patients had no pain, eight (33%) had occasional slight
      pain, three (13%) had pain with unusual activity, and four (17%) had moderate
      pain. No patient had marked pain or pain at rest. Average active forward
      elevation was 110 degrees , average passive forward elevation was 139 degrees ,
      average active external rotation was 31 degrees , and average passive internal
      rotation was to the L1 level. Active forward elevation of patients younger than
      60 years old was significantly greater than that of older patients. Functional
      outcome was variable. Although most patients could perform activities below the
      shoulder, only about one half could perform activities at or above the shoulder
      level. Eighty-nine percent of patients were satisfied with their treatment.
      Humeral head replacement for acute, four-part fractures reliably prevented the
      development of shoulder pain. Functional outcome varied and was dependent on
      patient age, individual functional requirements, and rotator cuff integrity.

PMID- 22959505
TI  - Anatomic determination of humeral head retroversion: The relationship of the
      central axis of the humeral head to the bicipital groove.
AB  - The relationship of the central axis of the humeral head to the bicipital groove
      was studied in 18 fresh cadaver specimens. The central axis was an average of 9
      mm posterior to the posterior margin of the bicipital groove. In reproduction of
      humeral head retroversion during humeral head replacement surgery, the lateral
      fin of the prosthesis should be placed at this location.

PMID- 22959506
TI  - The infraspinatus test: An early diagnostic sign of muscle weakness during
      external rotation of the shoulder in athletes.
AB  - Fifty-two men successively elevated dumbbells in increments of 0.5 kg from 1 to 9
      kg, performing external rotation of the shoulder with the elbow at 90 degrees  of
      flexion and the forearm at neutral rotation, while lying in the lateral position.
      Mean values and standard deviations of maximum weight elevated above the
      horizontal level by the dominant and nondominant arms of 49 men, excluding three
      athletes with marked infraspinatus muscle atrophy, ranged from 6.2 +/- 1.12 kg to
      6.7 +/- 1.11 kg. Considering the contribution of the infraspinatus muscle to the
      strength of shoulder external rotation, the elevation of a 3 kg dumbbell, called
      the "infraspinatus test," is considered to be an early diagnostic sign of muscle
      weakness during external rotation of the shoulder in athletes who have insidious
      infraspinatus muscle atrophy.

PMID- 22959508
TI  - Radial head fractures: Diagnosis and management.

PMID- 22959507
TI  - Reconstruction of the antero-superior shoulder capsule with the subscapularis
      tendon: A case report.
AB  - A 14-year-old boy presented with recurrent, anteroinferior, and multidirectional
      instability of his dominant shoulder. Examination with the patient under
      anesthesia demonstrated marked anterior and inferior translation when drawer
      testing was performed in adduction; however, abduction of the shoulder reduced
      the magnitude of humeral head translation in both these directions. Arthroscopy
      and open surgical dissection revealed the absence of any capsuloligamentous
      structures above the anterior band of the inferior glenohumeral ligament complex.
      This superior capsular defect could not be closed by a capsular shift procedure;
      therefore it was reconstructed with a portion of the subscapularis tendon. This
      case provides a clinical correlation of capsular anatomy with laxity on drawer
      testing. The glenohumeral laxity documented on examination with the patient under
      anesthesia supports experimental ligament-cutting studies that suggest the
      inferior glenohumeral ligament complex is the important stabilizer in abduction,
      whereas the superior and middle glenohumeral ligaments are more important in
      adduction.

PMID- 22959509
TI  - MiR-15a, miR-16-1 and miR-17-92 cluster expression are linked to poor prognosis
      in multiple myeloma.
AB  - Multiple myeloma (MM) is characterized by a profound genomic instability of
      potential prognostic relevance. Loss of chromosome 13, observed in almost half of
      patients, negatively affects prognosis. MiR-15a, miR16-1 and miR-17-92 cluster,
      located on 13q, play important roles in the regulation of cell proliferation,
      differentiation and apoptosis. Therefore, we investigated a possible correlation
      of miRNA expression with chromosome 13 deletions (del(13)) and prognosis. We
      measured the expression of miR-15a, miR16-1 in 70 newly diagnosed MM patients and
      miR-17-92 cluster in 85 newly diagnosed MM patients by quantitative real-time PCR
      analyses. MiR-15a, miR-16-1 and miR-17-92 cluster expression levels are
      independent of the del(13). High levels of miR-15a, miR-16-1, miR-17, miR-20a and
      miR-92-1 are associated with shorter progression-free survival (PFS), suggesting
      poor prognosis. Our data suggest that the expression of specific miRNAs may be
      contributing to MM prognosis.

PMID- 22959510
TI  - New therapeutics for myelodysplastic syndromes.
AB  - While MDS was only recently viewed as an orphan disease without any FDA approved
      therapeutic options, the landscape has changed dramatically with a promise for
      development of exciting new therapeutics that parallels our growing understanding
      of the pathobiology of the disease. An array of new agents is entering clinical
      development, many of which were not discussed in this review. Nevertheless, our
      paradigm for the approach to treatment of MDS can be expected to evolve with our
      ever expanding insight into the disease biology, targeting not only the MDS
      clone, but also the surrounding microenvironment while at the same time
      considering the context of the dynamics of disease pathogenesis.

PMID- 22959511
TI  - Endoplasmic reticulum stress contributes to arsenic trioxide-induced apoptosis in
      drug-sensitive and -resistant leukemia cells.
AB  - This study characterized the role of endoplasmic reticulum stress (ERS)-related
      pathways in arsenic trioxide-induced apoptosis in multidrug-resistant leukemia
      K562/ADM cells. Arsenic trioxide exposure led to much significant induction of
      apoptosis in K562/ADM cells than the parental K562 cells, and the chaperone
      proteins glucose-regulated protein 78, CHOP/GADD153, X-box binding protein-1 and
      caspase-12 were activated to varying degrees. Furthermore, arsenic trioxide
      stimulation led to inhibition of P-glycoprotein and Bcl-2 expression. This study
      demonstrates a missing link between arsenic trioxide and ERS-induced apoptosis,
      and suggests that the greater effects obtained in drug-resistant K562/ADM cells
      may be mediated by downregulation of P-glycoprotein and Bcl-2 expression.

PMID- 22959512
TI  - Sexual performance and stress response of previously unknown rams after grouping
      them in dyads.
AB  - The establishment and maintenance of individual social status is a stressor that
      affects negatively the reproductive function. Therefore, the aims of this study
      were to determine if after grouping two unknown rams there is a stress response,
      and their sexual behavior is affected, and if those responses differ between the
      rams that resulted dominants and those that resulted subordinates. Twelve adult
      rams were maintained in individual pens for one month, and on Day 0, hour 0 two
      rams of similar body weight were grouped in a neutral pen. Social rank was
      determined using the food competition test, in which each pair of rams was
      allowed to compete for feed in a bucket only large enough for one of them; the
      ram that was able to eat from the bucket for more than 1 min, was considered to
      be the dominant individual. Cortisol concentrations were measured on Day 0 during
      the first 12h after grouping. Testosterone concentrations were measured from Day 
      9 to Day 16. Sexual behavior of rams toward estrus ewes was determined before and
      after grouping in individual pen tests. There was no difference between dominant
      and subordinated rams in none of the studied variables. Cortisol concentration
      had a peak 30 min after grouping the rams (P<0.0001). There was a significant
      decrease in testosterone concentration on Day 5 and Days 8-14 compared to
      concentration before grouping (P=0.02). The frequency of ano-genital sniffing and
      flehmen of estrus ewes decreased after grouping, with no differences between
      dominant and subordinated rams (P=0.009 and 0.03 ano-genital sniffing and
      flehmen, respectively). However, the frequency of lateral approaches (P=0.005),
      and all mating behaviors towards ewes increased after grouping the rams (mount
      attempts: P=0.02; mounts: P=0.008; mounts with ejaculation: P=0.05; total mounts:
      P=0.003; ejaculation/total mounts: P=0.0004). It was concluded that grouping
      unknown rams modified their sexual strategy resulting in an increase in the
      number of mating behaviors when rams were tested alone with estrus ewes. However,
      grouping two unfamiliar rams was a stressful event that negatively affected
      testosterone concentrations but the stress and behavior responses did not differ
      according to rams' social rank.

PMID- 22959513
TI  - Intrauterine ozone treatment of retained fetal membrane in Simmental cows.
AB  - The aim of research was to determine influence of intrauterine application of two
      different ozone preparations on reproductive performance in Simmental cows with
      retained fetal membranes (RFM). The study was performed on 143 Simmental cows
      aged 2-8 years and divided in three groups. Group A (n=46) consisted of cows
      treated with foam spray ozone applied into the body of the uterus for 5s using a
      sterile catheter. Group B (n=50) consisted of cows treated using six ozone pearls
      intrauterinely at once, as deeply and hygienically possible. Cows were observed
      and treated during early puerperium, 24-36h after parturition. The third group
      (n=47) consisted of cows without RFM (control group). To assess the reproductive
      performance of cows, the interval from calving to first insemination (days not
      pregnant to first service, DOFS), interval from calving to pregnancy (days not
      pregnant to pregnancy, DOP), relative pregnancy rate (%), first service
      conception rate (FSCR, %) and all service conception rate (ASCR, %) were
      measured. The estimate of hazard ratio for the Groups A and B relative to control
      group with DOFS were 0.423 (P=0.0006) and 0.434 (P=0.0005), and with DOP were
      0.701 (P=0.003) and 0.411 (P=0.0003), respectively, implying that cows in the
      control group were not pregnant longer until first insemination and pregnancy.
      Variables that had an influence on DOFS were postpartum fever (PPF) (HR=0.458;
      P=0.003) and milk yield (HR=0.999; P<0.0001) and an influence on DOP were PPF
      (HR=0.314; P=0.001) and milk yield (HR=0.999; P<0.0001). Cows with RFM treated
      with intrauterine Riger spray or Ripromed ovuli O(3) have similar or enhanced
      reproductive performance results compared to the control group of cows
      demonstrating the effectiveness of therapy with intrauterine ozone products.

PMID- 22959514
TI  - Association of prolactin haplotypes with reproductive traits in Tsaiya ducks.
AB  - A previous cDNA microarray study showed that the prolactin (PRL) gene may be
      involved in the duck ovarian follicle development and egg formation process. The
      purpose of this study was to investigate the relationship between PRL genotypes
      of single nucleotide polymorphism (SNP) and reproductive traits of Tsaiya ducks.
      Primer pairs for the coding regions in the PRL were designed based on the duck
      genomic sequence database. Polymorphisms were detected by polymerase chain
      reaction (PCR)-single strand polymorphism (SSCP) and were verified by DNA
      sequencing. Six novel SNPs (T233C, T295C, G309T, C381A, G3941T and A3975C) were
      identified in the 1972 bp region of duck PRL gene, and all of them were located
      in non-coding regions. Single SNP-trait association analysis showed that each SNP
      was associated with at least one duck reproductive trait (P<0.05). Haplotype
      combinations constructed on these SNPs were associated with egg weight at 40
      weeks of age (EW40), fertility rate (FR) and maximum duration of fertility (MDF)
      (P<0.0001). In particular, diplotype H1H2 had positive effect on EW40, whereas it
      had negative effect on FR and MDF (P<0.05). Positive effects of the diplotype
      H1H5 were observed for FR and MDF, but a negative effect was observed for EW40
      (P<0.05). This suggested that the PRL gene plays an important role in the
      regulation of egg weight and fertility-related traits and could be a potential
      marker in a marker assisted selection program during duck balancing selection.
      Further investigations on more duck populations with large sample sizes are
      needed to confirm this finding.

PMID- 22959515
TI  - Expression of leptin and its receptor in corpus luteum during estrous cycle in
      buffalo (Bubalus bubalis).
AB  - Leptin is supposed to play a crucial role in ovarian luteal dynamics. The present
      study was aimed to investigate the importance of leptin and its receptors in
      buffalo corpus luteum (CL) obtained from different stages of the estrous cycle.
      Real-time RT-PCR (qPCR), western blot and immunohistochemistry techniques were
      applied to investigate mRNA expression, protein expression and localization of
      examined factors. Additionally to assess the contribution of leptin in
      progesterone production the expression profiles of StAR, P450scc and HSD were
      also investigated. In general, we demonstrated presence of leptin and its
      receptors in buffalo CL during the estrous cycle. The mRNA levels of leptin and
      its receptors were significantly up regulated in (P<0.05) in all the stages and
      highest levels were observed in mid and late luteal stages consistent with in
      vivo luteinization of buffalo CL and declined coincidental to luteal regression.
      The expression of StAR, P450scc and HSD factors maintained low in early luteal
      phase, after that level of expression increased steadily to show a significant
      rise (P<0.05) in mid luteal phase followed by gradual decline in late luteal
      phase and regressed CL and this correlates well with the Ob and ObR receptor
      activity, verifying their key role in progesterone and other steroids production
      in functional CL. As revealed by immunohistochemistry, leptin protein was
      localized predominantly in large luteal cells however leptin receptor (Ob-R) was
      localized in large luteal cells as well as in endothelial cells. It can be
      concluded from our study that leptin via its autocrine/paracrine effects play a
      significant role in promoting angiogenesis, steroidogenesis and also acts as key
      survival factor in bubaline CL.

PMID- 22959516
TI  - Pharmacological treatment of lower urinary tract symptoms in men: implementation
      of recommendations in clinical practice.
AB  - CONTEXT: Introducing a consensus on pharmacological treatment of male LUTs to be
      applied to Urology Primary Care. EVIDENCE COMPILATION: The consensus has been
      created by an expert committee based on the latest recommendations by the
      European and American Guides for male LUTs treatment. Also, a bibliographic
      review of the latest advances in the therapeutical approach to these patients has
      been carried out. EVIDENCE SYNTHESIS: Although the prevalence of both LUTs and
      overactive bladder is high, and its impact on the quality of life and social cost
      have been widely described, the number of patients treated is low. On the other
      hand, current clinical practice doesn't necessarily match the Guides and for this
      reason false perceptions of the available treatments circulate. For instance, men
      with storage LUTS are often treated inadequately with alpha-blockers or 5-alpha
      reductase inhibitors due to underlying obstructive disorders. However, it is
      known that the incidence of real obstruction tends to be low. Current evidence,
      though limited, shows that antimuscarinic drugs may be used safely by men with
      LUTs, and are not associated with an increase in the prevalence of high urinary
      retention. CONCLUSION: We propose an algorithm for the management of male LUTs in
      which various levels of clinical evaluation are shown for a specific diagnose, as
      well as for choosing the most appropriate treatment.

PMID- 22959517
TI  - Synthesis and SAR of 2',3'-bis-O-substituted N(6), 5'-bis-ureidoadenosine
      derivatives: implications for prodrug delivery and mechanism of action.
AB  - A series of 2',3'-bis-O-silylated or -acylated derivatives of lead compound 3a
      (2',3'-bis-O-tert-butyldimethylsilyl-5'-deoxy-5'-(N-methylcarbamoyl)amino-N(6)-(N
      phenylcarbamoyl)adenosine) were prepared and evaluated for antiproliferative
      activity against a panel of murine and human cancer cell lines (L1210, FM3A, CEM,
      and HeLa). 2',3'-O-Silyl groups investigated included triethylsilyl (10a), tert
      butyldiphenylsilyl (10b), and triisopropylsilyl (10c). 2',3'-O-Acyl groups
      investigated included acetyl (13a), benzoyl (13b), isobutyryl (13c), butanoyl
      (13d), pivaloyl (13e), hexanoyl (13f), octanoyl (13g), decanoyl (13h), and
      hexadecanoyl (13i). IC(50) values ranged from 3.0+/-0.3 to >200MUg/mL, with no
      improvement relative to lead compound 3a. Derivative 10a was approximately
      equipotent to 3a, while compounds 13e-g were from three to fivefold less potent,
      and all other compounds were significantly much less active. A desilylated
      derivative (5'-deoxy-5'-(N-methylcarbamoyl)amino-N(6)-(N
      phenylcarbamoyl)adenosine; 5) and several representative derivatives from each
      subgroup (10a-10c, 13a-13c) were screened for binding affinity for bone
      morphogenetic protein receptor 1b (BMPR1b). Only compound 5 showed appreciable
      affinity (K(d)=11.7+/-0.5MUM), consistent with the inference that 3a may act as a
      prodrug depot form of the biologically active derivative 5. Docking studies
      (Surflex Dock, Sybyl X 1.3) for compounds 3a and 5 support this conclusion.

PMID- 22959518
TI  - Newly synthesized bis-benzimidazole derivatives exerting anti-tumor activity
      through induction of apoptosis and autophagy.
AB  - In this study, a new series of bis-benzimidazole derivatives were designed and
      synthesized. Most of these new compounds showed significant anti-tumor activity
      in vitro compared to Hoechst 33258. Among them, the most potent compound 8 had
      the IC(50) values of 0.56MUM for HL60 (Human promyelocytic leukemia cells) tumor
      cell line and 0.58MUM for U937 (Human leukemic monocyte lymphoma cells) tumor
      cell line. Subsequent toxicity study on human peripheral blood mononuclear cells
      (PBMC) showed that compound 8 exhibited less toxicity than 5-FU. We also found
      that apoptosis and autophagy were simultaneously induced by compound 8 in HL60
      cells, and inhibition of autophagy by 3-MA decreased compound 8-induced
      apoptosis, indicating that they acted in synergy to exert tumor cell death.

PMID- 22959519
TI  - Small molecule activators of proteasome-related HslV peptidase.
AB  - The HslVU is the proteasome-related two component system composed of HslV
      peptidase and HslU chaperone. It is involved in the degradation of an array of
      intracellular proteins. The presence of HslVU homologs in pathogenic microbes and
      its absence in human makes it an antimicrobial drug target. The functional HslVU
      complex forms when HslV dodecamer is flanked at both ends by HslU hexamers. In
      the HslVU complex, eight residues at the carboxy termini of HslU subunits
      intercalate into a clefts between two adjacent HslV subunits causing a
      conformational change in the active site of HslV which in turn results in the
      allosteric activation of HslV peptidase. Here, we report small molecules capable
      of activating HslV peptidase in the absence of its natural activator HslU ATPase.
      For this purpose, virtual screening of an in-house library of synthetic and
      natural compounds was performed to find out ligands mimicking the interaction of
      HslU carboxy terminus with HslV dodecamer. The benzimidazole, quinazoline and
      chromone derivatives were suggested by ligand docking to bind at the HslU carboxy
      termini intercalation pockets in the HslV dodecamer. This was confirmed by HslV
      activation and isothermal titration calorimetry assays with these compounds that
      gave ED(50) in sub-micromolar range (0.6-1.5MUM). The results showed for the
      first time that small, extracellular non-peptidic molecules can allosterically
      activate the peptide hydrolytic activity of HslV which in turn would initiate
      intracellular proteolysis.

PMID- 22959520
TI  - Biosynthesis of anti-HCV compounds using thermophilic microorganisms.
AB  - This work describes the application of thermophilic microorganisms for obtaining
      6-halogenated purine nucleosides. Biosynthesis of 6-chloropurine-2'-deoxyriboside
      and 6-chloropurine riboside was achieved by Geobacillus stearothermophilus CECT
      43 with a conversion of 90% and 68%, respectively. Furthermore, the selected
      microorganism was satisfactorily stabilized by immobilization in an agarose
      matrix. This biocatalyst can be reused at least 70 times without significant loss
      of activity, obtaining 379mg/L of 6-chloropurine-2'-deoxyriboside. The obtained
      compounds can be used as antiviral agents.

PMID- 22959521
TI  - Molecular beacon-based quantitiation of epithelial tumor marker mucin 1.
AB  - Mucin 1 (Muc1) is a glycoprotein expressed on most epithelial cell surfaces,
      which has been confirmed as a useful biomarker for the diagnosis of early
      cancers. In this study, we demonstrate that a quantum dot (QD)-aptamer beacon
      acts by folding-induced dissociation of a DNA intercalating dye, BOBO-3, in the
      presence of the target molecules, Muc1. Release of intercalated BOBO-3s from the
      QD-conjugated aptamers results in a decrease in QD fluorescence resonance energy
      transfer (FRET)-mediated BOBO-3 emission, allowing for label-free Muc1 detection
      and quantitation. We attain highly specific and wide-range detection (from 50nM
      to 20MUM) of Muc1, suggesting that our QD-aptamer beacon can be a potential
      alternative to immuno-based assays for Muc1 detection. The detection methodology
      is expected to be improved for the early diagnosis of different types of
      epithelial cancers of large populations.

PMID- 22959522
TI  - The association between polymorphisms in prooxidant or antioxidant enzymes
      (myeloperoxidase, SOD2, and CAT) and genes and prostate cancer risk in the
      Chinese population of Han nationality.
AB  - BACKGROUND: Oxidative stress was associated with prostate cancer (PCa). The
      expressions of prooxidant or antioxidant enzymes (myeloperoxidase [MPO],
      superoxide dismutase (SOD2), and catalase (CAT)) have been proved to be related
      to gene polymorphisms. Our study aimed to evaluate the association between
      genetic polymorphisms and the risk of PCa. METHODS: Genotyping was carried out by
      genotyping system (MassARRAY iPLEX; Sequenom Inc, San Diego, CA) in 1388 patients
      with PCa and 1008 cancer-free controls in the Chinese population. RESULTS: One
      SNP of SOD2 (rs5746136; P < .050, odds ratios (OR), 0.8806) was significant.
      Another SNP was shown to have limited association with the risk of PCa (rs554518;
      P = .09443) in all SNPs of CAT. In other SNPs, no significant difference was
      shown between genotype distributions in the patients with PCa and the control
      group. CONCLUSIONS: Our data showed that rs5746136 of SOD2 was associated with
      susceptibility to PCa in the Chinese population of Han nationality. The possible
      association between rs8082134 of CAT and PCa risk needs further verification.

PMID- 22959523
TI  - [Comment to "Analysis of predictive factors of success for prostate
      photovaporization in BPH by greenlight laser"].

PMID- 22959524
TI  - Locking plate fixation of fractures of the proximal humerus: analysis of
      complications, revision strategies and outcome.
AB  - BACKGROUND: Locking plates for open reduction-internal fixation (ORIF) of
      proximal humeral fractures are widely used. We observed an unusually high number
      of patients with complications referred to our institution. It was the purpose of
      this study to report these complications, as well as their treatment and outcome.
      MATERIALS AND METHODS: From 2003 to 2010, all patients treated for complications
      after ORIF with locking plates for proximal humeral fractures were prospectively
      collected and retrospectively analyzed. Patients were followed up clinically and
      radiographically. RESULTS: In total, 121 patients (67 women and 54 men; mean age,
      59 years) were referred after primary locking plate ORIF; 80% had a 3- or 4-part
      fracture. A mean of 3 complications occurred per patient, including malreduction,
      primary screw cutout, malunion, nonunion, avascular necrosis, and infection.
      Secondary screw cutout was found in 57% of patients, causing glenoid destruction
      in 33% of patients. A mean of 1.5 revision surgeries were needed.
      Hemiarthroplasty, total shoulder arthroplasty, and reverse shoulder arthroplasty
      improved the mean Constant score (24 to 55 points, P < .05; 29 to 54 points, P =
      .3; and 25 to 48 points, P < .05, respectively) after a mean of 24 months. In 6
      patients, glenoid implantation was no longer possible because of the destruction
      by perforated head screws. CONCLUSION: In this negatively selected series,
      complications resulted in secondary arthroplasties in over 50% of the patients.
      Shoulder function, though improved, remained substantially restricted even after
      revision surgery. Glenoid destruction by locking screws was the most devastating
      and previously almost unseen complication, which limited the options of
      treatment.

PMID- 22959525
TI  - Results of total shoulder arthroplasty with a monoblock porous tantalum glenoid
      component: a prospective minimum 2-year follow-up study.
AB  - BACKGROUND: Aseptic loosening of all-polyethylene glenoid components remains a
      limiting factor in achieving long-term implant survival in total shoulder
      arthroplasty (TSA). This study prospectively evaluated the functional and
      radiographic outcomes of patients undergoing TSA with a novel, porous, tantalum
      backed glenoid component, with a minimum 2 years of follow-up. MATERIALS AND
      METHODS: Porous tantalum-backed glenoid components were used in 19 TSAs in 19
      patients. All patients were available for radiographic follow-up at an average of
      38 months (range, 24-64 months). Patients were evaluated prospectively using the
      American Shoulder and Elbow Surgeons (ASES) score and pain on a visual analog
      scale (VAS). Radiographs were evaluated for component loosening and failure of
      the porous tantalum backing at a minimum 2 years of follow-up. RESULTS: The mean
      VAS decreased from 8.6 to 2.9 (P < .0001). The mean ASES score improved from 21
      to 70 points (P < .05). Mean active forward elevation improved from 75 degrees 
      to 131 degrees  (P < .0001). At latest follow-up, all glenoid components except 1
      had complete in-growth of the porous tantalum keel; however, 4 components (21%)
      failed by fracture at the keel-glenoid face junction. CONCLUSIONS: There was an
      unacceptably high rate of glenoid component failure (21%) due to fracture at the
      keel-glenoid face junction in this series. The manufacturer has subsequently
      revised this early design to reduce the risk of failure. The results of this
      study illustrate that caution should be exercised in the use of novel implants
      with an unproven clinical track record.

PMID- 22959526
TI  - Identification of novel alpha7 nicotinic receptor ligands by in silico screening
      against the crystal structure of a chimeric alpha7 receptor ligand binding
      domain.
AB  - A hierarchical in silico screening procedure using the crystal structure of an
      agonist bound chimeric alpha7/Ls-AChBP protein was successfully applied to both
      proprietary and commercial databases containing drug-like molecules. An overall
      hit rate of 26% (pK(i) >=5.0) was obtained, with an even better hit rate of 35%
      for the commercial compound collection. Structurally novel and diverse ligands
      were identified. Binding studies with [(3)H]epibatidine on chimeric alpha7/5
      HT(3) receptors yielded submicromolar inhibition constants for identified hits.
      Compared to a previous screening procedure that utilized the wild type Ls-AChBP
      crystal structure, the current study shows that the recently obtained alpha7/Ls
      AChBP chimeric protein crystal structure is a better template for the
      identification of novel alpha7 receptor ligands.

PMID- 22959527
TI  - Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities
      of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer
      cells.
AB  - A series of new heterocyclic derivatives of ursolic acid 1 were synthesized and
      evaluated for their antiproliferative activity against AsPC-1 pancreatic cancer
      cells. Compounds 24-32, with an alpha,beta unsaturated ketone in conjugation with
      an heterocyclic ring in ring A have improved antiproliferative activities.
      Compound 32 is the most active compound with an IC(50) of 1.9 MUM which is
      sevenfold more active than ursolic acid 1. Compound 32 arrests cell cycle in G1
      phase and induces apoptosis in AsPC-1 cells with upregulation of p53, p21(waf1)
      and NOXA protein levels.

PMID- 22959528
TI  - Novel system identification method and multi-objective-optimal multivariable
      disturbance observer for electric wheelchair.
AB  - Electric wheelchair (EW) is subject to diverse types of terrains and slopes, but
      also to occupants of various weights, which causes the EW to suffer from highly
      perturbed dynamics. A precise multivariable dynamics of the EW is obtained using
      Lagrange equations of motion which models effects of slopes as output-additive
      disturbances. A static pre-compensator is analytically devised which considerably
      decouples the EW's dynamics and also brings about a more accurate identification
      of the EW. The controller is designed with a disturbance-observer (DOB) two
      degree-of-freedom architecture, which reduces sensitivity to the model
      uncertainties while enhancing rejection of the disturbances. Upon disturbance
      rejection, noise reduction, and robust stability of the control system, three
      fitness functions are presented by which the DOB is tuned using a multi-objective
      optimization (MOO) approach namely non-dominated sorting genetic algorithm-II
      (NSGA-II). Finally, experimental results show desirable performance and robust
      stability of the proposed algorithm.

PMID- 22959530
TI  - The association between absent lunula and depression in depressive outpatients: a
      case-control study.
AB  - Absent lunula can progressively develop in a person who previously had a normal
      sized lunula and can be associated with various systemic disorders. In this case
      control study we hypothesised that absent lunula is associated with depression.
      The study comprised 332 depressive outpatients as well as 367 age- and sex
      matched controls, all of whom were assessed and screened by the Zung Self-rating
      Depression Scale (ZSDS). The presence of absent lunula in all fingers except the
      little finger on the right hand of subjects was examined and the number of absent
      lunula was calculated as 0, 1, 2, 3 and 4. It was revealed that there was no
      significant difference in age and gender between controls and depressive
      outpatients. In the order of 0, 1, 2, 3 and 4 absent lunula, the percentages were
      68.1, 7.4, 9.5, 5.2 and 9.8 in controls, while it was 17.2, 15.4, 22.3, 21.4 and
      23.7 in depressive outpatients with significant difference while they were 17.2,
      15.4, 22.3, 21.4 and 23.7 in depressive outpatients, significantly different
      compared with controls. Logistic regression analysis on depressive outpatients
      indicated that severe depression was not associated with age and sex but markedly
      associated with number of absent lunula. Our study found that depression was
      associated with absent lunula, and severe depression was associated with a
      greater number of absent lunula.

PMID- 22959529
TI  - How are inner hair cells stimulated? Evidence for multiple mechanical drives.
AB  - Recent studies indicate that the gap over outer hair cells (OHCs) between the
      reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during
      low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in
      the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap
      changes reveals three IHC drives in addition to classic SHEAR. For upward basilar
      membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction
      by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA
      SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL,
      compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby
      producing an outward (away from the IHCs) radial fluid flow which is the OHC
      MOTILITY drive. For upward BM motion, the force that moves the TM upward also
      compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is
      the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze
      the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the
      CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high
      sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and
      medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the
      ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and
      chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after
      OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC
      MOTILITY drive provides another mechanism, in addition to BM motion
      amplification, that uses active processes to enhance the output of the cochlea.
      The ability of these IHC drives to explain previously anomalous data provides
      strong, although indirect, evidence that these drives are significant and
      presents a new view of how the cochlea works at frequencies below 3 kHz.

PMID- 22959531
TI  - A diterpene synthase from the clary sage Salvia sclarea catalyzes the cyclization
      of geranylgeranyl diphosphate to (8R)-hydroxy-copalyl diphosphate.
AB  - The bicyclic diterpene (-)-sclareol is accumulated in glandular trichomes in
      Salvia sclarea (Schmiderer et al., 2008), and is a major terpenoid component of
      this plant species. It is used as the starting material for Ambrox synthesis, a
      synthetic ambergris analog used in the flavor and fragrance industry. In order to
      investigate the formation of sclareol, cDNA prepared from secretory cells of
      glandular trichomes from S. sclarea inflorescence were randomly sequenced. A
      putative copalyl diphosphate synthase encoding EST, SscTPS1, was functionally
      expressed in Escherichia coli. Whereas reaction of geranylgeranyl diphosphate
      with the putative copalyl diphosphate synthase followed by hydrolysis with
      alkaline phosphatase yielded a diastereomeric mixture of (13R)- and (13S)-manoyl
      oxide, HCl hydrolysis yielded (-)-sclareol (1) and 13-epi-sclareol as products.
      The product of the reaction of SscTPS1 with geranylgeranyl diphosphate was
      subjected to analysis by LC-negative ion ESI-MS/MS without prior hydrolysis. EPI
      scans were consistent with copalyl diphosphate to which 18 mass units had added
      (m/z 467 [M+H](-)). The enzymatic reaction was also carried out in the presence
      of 60% H2(18)O. LC-negative ion ESI-MS/MS analysis established an additional
      reaction product consistent with the incorporation of (18)O. Incubation in the
      presence of 60% (2)H2O resulted in the incorporation of one deuterium atom. These
      results suggest water capture of the carbocation intermediate, which is known to
      occur in reactions catalyzed by monoterpene synthases, but has been described
      only several times for diterpene synthases.

PMID- 22959532
TI  - Terpene and lignan glycosides from the twigs and leaves of an endangered conifer,
      Cathaya argyrophylla.
AB  - Labdane diterpene glycosides cathargyroside A and cathargyroside B, monoterpene
      glycosides vervenone-10-O-beta-D-glucopyranoside and vervenone-10-O-beta-D
      apiofuranosyl-(1"->6')-beta-D-glucopyranoside, as well as lignan glycosides
      cedrusinin-4-O-alpha-L-rhamnopyranoside and (+)-cyclo-olivil-9'-O-beta-D
      xylopyranoside, along with 39 known compounds, were obtained from the methanol
      extract of the twigs and leaves of Cathaya argyrophylla. These compounds were
      identified mainly by analyzing their NMR and MS data. Almost all of these
      compounds were hitherto unknown in this genus. The isolated compounds were
      screened against Candida albicans and Staphylococcus aureus for antimicrobial
      assay, and against K562, HT-29, BEL-7402, SGC-7901, B16, BGC-823, U251 and A549
      cancer cell lines for cytotoxic activities. One compound showed antimicrobial
      activity against C. albicans, and four of them displayed cytotoxicity. Similarity
      analysis on the chemical constituents of the genera Cathaya, Picea and Pinus
      supported their close phylogenetic relationships.

PMID- 22959533
TI  - Rehabilitation of the medial- and lateral collateral ligament-deficient elbow: an
      in vitro biomechanical study.
AB  - DESIGN: In vitro biomechanical research using an elbow motion simulator.
      INTRODUCTION: The optimal rehabilitation of elbow dislocations with medial
      collateral ligament (MCL) and lateral collateral ligament (LCL) injuries has not
      been defined. PURPOSE: To determine a safe rehabilitation protocol for elbow
      dislocations with MCL and LCL injuries. METHODS: Eight cadaveric elbows underwent
      simulated active and passive motions with the arm in multiple orientations. Varus
      valgus angulation and internal-external rotation of the ulna relative to the
      humerus were quantified for the intact joint and with injured MCL and LCL.
      RESULTS: Active motion with injured MCL and LCL in the horizontal and vertical
      orientations resulted in kinematics similar to the intact elbow, whereas passive
      motion resulted in significant kinematic alterations. Marked elbow instability
      was noted in the varus and valgus orientations using both active and passive
      motion. CONCLUSIONS: Elbows with MCL and LCL injuries should be rehabilitated
      using active motion in the horizontal or vertical orientations. LEVEL OF
      EVIDENCE: Basic science research.

PMID- 22959534
TI  - Our sufficiency-of-proof thresholds.

PMID- 22959535
TI  - Letter on "Validation of the Brief International Classification of Functioning,
      Disability, and Health (ICF) Core Set for Hand Conditions".

PMID- 22959536
TI  - "A 'one-piece' gutter orthosis/strapping alternative".
AB  - Patients often have difficulty securing and positioning finger orthoses
      (splints). Using standard strapping materials molded directly into the orthotic
      device, this author describes an alternative strapping system for these small
      finger orthoses. -Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor.

PMID- 22959537
TI  - A potential classification model for individuals with tennis elbow.
AB  - The complexities associated with the anatomy, biomechanics, and pathophysiology
      of lateral epicondylalgia have resulted in numerous treatment options for this
      common overuse syndrome. Choosing an appropriate treatment option from such an
      array can be challenging. To assist therapists with this challenge, these authors
      created a classification model that categorizes patients by using information
      from common signs and symptoms. Such categorization can assist therapists in
      identifying appropriate treatment options

PMID- 22959538
TI  - Clinical commentary in response to: "Rehabilitation protocol after suspension
      arthroplasty of thumb carpometacarpal joint osteoarthritis".

PMID- 22959539
TI  - Venous thromboembolism: advances and controversies. Preface.

PMID- 22959540
TI  - Venous thromboembolism: epidemiology and magnitude of the problem.
AB  - Pulmonary embolism is the third most common cardiovascular disease after
      myocardial infarction and stroke. The death rate from pulmonary embolism exceeds
      the death rate from myocardial infarction, because myocardial infarction is much
      easier to detect and to treat. Among survivors of pulmonary embolism, chronic
      thromboembolic pulmonary hypertension occurs in 2-4 of every 100 patients. Post
      thrombotic syndrome of the legs, characterized by chronic venous insufficiency,
      occurs in up to half of patients who suffer deep vein thrombosis or pulmonary
      embolism. We have effective pharmacological regimens using fixed low dose
      unfractionated or low molecular weight heparin to prevent venous thromboembolism
      among hospitalized patients. There remains the problem of low rates of
      utilization of pharmacological prophylaxis. The biggest change in our
      understanding of the epidemiology of venous thromboembolism is that we now
      believe that deep vein thrombosis and pulmonary embolism share similar risk
      factors and pathophysiology with atherothrombosis and coronary artery disease.

PMID- 22959541
TI  - Clinical presentation of deep vein thrombosis and pulmonary embolism.
AB  - BACKGROUND: In the past, the clinical diagnosis of venous thromboembolism (VTE),
      which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE) had been
      very challenging, because clinical presentation is non-specific and inaccurate.
      OBJECTIVE: To review and assess clinical signs, symptoms and risk factors of DVT
      and PE and identify most common differential diagnoses. RESULTS: Important
      components for the clinical diagnosis of VTE include risk factors such as
      immobilization, presence of cancer, confinement to bed, previous major surgery,
      prior VTE and - specific for DVT - whole limb enlargement, one-sided calf
      enlargement and dilatation of superficial veins. Additional items specific for PE
      include tachycardia, dyspnea chest pain and hemoptysis. Many of these clinical
      characteristics are included into clinical prediction rules, such as the Wells
      pre-test probability score for DVT or PE or the Geneva score for PE. These scores
      are used to determine the pre-test probability for VTE and they constitute the
      basis for a diagnostic algorithm. Various clinical prediction rules for DVT or PE
      show comparable accuracy. CONCLUSION: Even though the clinical presentation of
      DVT and PE varies substantially in individual patients and settings and may be
      misleading, diagnostic prediction rules based on clinical presentation and risk
      factors are very useful to assess pre-test probability, which is a very important
      concept for the diagnosis of DVT and PE.

PMID- 22959542
TI  - Abdominal thromboses of splanchnic, renal and ovarian veins.
AB  - Thromboses of abdominal veins outside the iliac-caval axis are rare but
      clinically relevant. Early deaths after splanchnic vein thrombosis occur in 5-30%
      of cases. Sequelae can be liver failure or bowel infarction after splanchnic vein
      thrombosis, renal insufficiency after renal vein thrombosis, ovarian infarction
      after ovarian vein thrombosis. Local cancer or infections are rare in Budd-Chiari
      syndrome, and common for other sites. Inherited thrombophilia is detected in 30
      50% of patients. Myeloproliferative neoplasms are the main cause of splanchnic
      vein thrombosis: 20-50% of patients have an overt myeloproliferative neoplasm
      and/or carry the molecular marker JAK2 V617F. Renal vein thrombosis is closely
      related to nephrotic syndrome; finally, ovarian vein thrombosis can complicate
      puerperium. Heparin is used for acute treatment, sometimes in conjunction with
      systemic or local thrombolysis. Vitamin K-antagonists are recommended for 3-6
      months, and long-term in patients with Budd-Chiari syndrome, unprovoked
      splanchnic vein thrombosis, or renal vein thrombosis with a permanent
      prothrombotic state such as nephrotic syndrome.

PMID- 22959543
TI  - Extra-abdominal venous thromboses at unusual sites.
AB  - Venous thrombosis typically involves the lower extremities. Rarely, it can occur
      in cerebral, splanchnic, or renal veins, with a frightening clinical impact.
      Other rare manifestations are upper-extremity deep vein thrombosis, that can
      complicate with pulmonary embolism and post-thrombotic syndrome, and retinal vein
      occlusion, significantly affecting the quality of life. This review is focused on
      venous thromboses at unusual extra-abdominal sites. Local infections or cancer
      are frequent in cerebral sinus-venous thrombosis. Upper-extremity deep vein
      thrombosis is mostly due to catheters or effort-related factors. Common risk
      factors are inherited thrombophilia and oral contraceptive use. Acute treatment
      is based on heparin; in cerebral sinus-venous thrombosis, local or systemic
      fibrinolysis should be considered in case of clinical deterioration. Vitamin-K
      antagonists are recommended for 3-6 months; indefinite anticoagulation is
      suggested for recurrent thrombosis or unprovoked thrombosis and permanent risk
      factors. However, such recommendations mainly derive from observational studies;
      there are no data about long-term treatment of retinal vein occlusion.

PMID- 22959544
TI  - Epidemiology, diagnosis, treatment and management of superficial-vein thrombosis
      of the legs.
AB  - Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially
      impact its clinical management. Particularly, the clear confirmation that SVT is
      closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE)
      highlights the potential severity of the disease. DVT or PE is diagnosed in 20
      30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic
      events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4
      8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg
      fondaparinux for 45 days, was demonstrated to be effective and safe for
      preventing these symptomatic thromboembolic events in patients with lower-limb
      isolated SVT in the randomized, placebo-controlled CALISTO study. More recent
      data from another randomized trial support these findings. New recommendations on
      the management of SVT patients, including complete ultrasonography examination of
      the legs and, in patients with isolated SVT, prescription of once-daily 2.5 mg
      fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be
      proposed, wherever the cost of fondaparinux is acceptable. Superficial-vein
      thrombosis (SVT) of the lower limbs has long been regarded as a benign, self
      limiting disease, expected to resolve spontaneously and rapidly, and requiring
      only symptomatic treatments [1,2]. However, the perception of this disease is now
      changing with the recent publication of data indicating its potential severity
      [3] and showing for the first time the benefit of a therapeutic strategy based on
      the administration of an anticoagulant treatment [4]. The overall management of
      this frequent disease therefore needs to be reconsidered.

PMID- 22959545
TI  - Thrombophilia and venous thromboembolism: RIETE experience.
AB  - RIETE is an ongoing registry of consecutive patients with acute venous
      thromboembolism (VTE). First we learned that in RIETE the prevalence of positive
      tests was 32%. One in every 2 patients younger than 50 years tested positive,
      with no differences between idiopathic or secondary, first event or recurrent
      VTE. In contrast, one in every 4 patients older than 50 years tested positive.
      Then, we found that the younger age of women with factor V Leiden or prothrombin
      G20210A may be attributed to the higher proportion of women who had the VTE
      during pregnancy or contraceptive use. At variance with this, 60% of men had
      idiopathic VTE, and only those with factor V Leiden were younger than those who
      tested negative. We need more patients, more data and a longer follow-up. In a
      near future we might be able to learn more about the outcome of VTE patients.

PMID- 22959546
TI  - Diagnosis of pulmonary embolism: Advances and pitfalls.
AB  - The signs and symptoms of patients with pulmonary embolism (PE) form a wide
      spectrum and considerably overlap with other cardiopulmonary diseases. Timely
      recognizing of this disease therefore remains challenging, but is of vital
      importance to avoid PE-related morbidity and mortality. To aid and standardize
      the initial diagnostic approach of patients with suspected PE, clinical
      probability rules have been developed and simplified for use in clinical
      practice. It has been demonstrated by clinical outcome studies that it is safe
      and of high clinical utility to exclude PE on the basis of an unlikely clinical
      probability and a normal D-dimer test result. For the remaining patients with
      suspected PE, imaging tests are required. The introduction of multi-detector
      computed tomographic pulmonary angiography (MD-CTA) has significantly improved
      the detection of PE, and this test is now regarded as the imaging test of first
      choice. This review will focus on recent advances and pitfalls that remain in the
      diagnostic work-up of patients with suspected acute PE.

PMID- 22959547
TI  - Clinical decision rules in venous thromboembolism.
AB  - Current prevention, diagnostic management and therapeutic management strategies
      for venous thromboembolism (VTE) almost all include an assessment of the clinical
      probability. Clinical decision rules (CDRs) are decision making tools using
      combinations of simple available clinical predictors to define a probability of
      an outcome which can be used in a preventative strategy, diagnostic course of
      action or therapeutic course of action. CDRs provide accurate and reproducible
      estimates of clinical outcomes. The best performing CDRs are built and validated
      following strict methodological standards. In this paper we critically review the
      use of CDRs in prevention, diagnosis and treatment of VTE and highlight those
      CDRs that are ready for the prime time of daily clinical use.

PMID- 22959548
TI  - Venous thromboembolism associated with pregnancy and hormonal therapy.
AB  - Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality
      during or early after pregnancy and in women taking hormonal therapy for
      contraception or for replacement therapy. Post-thrombotic syndrome, including leg
      oedema and leg pain, is an unrecognized burden after pregnancy-related VTE, which
      will affect more than two of five women. Women with a prior VTE, a family history
      of VTE, certain clinical risk factors and thrombophilia are at considerably
      increased risk both for pregnancy-related VTE and for VTE on hormonal therapy.
      This review critically assesses the epidemiology and risk factors for pregnancy
      related VTE and current guidelines for prophylaxis and treatment. We also provide
      information on the risk of VTE related to hormonal contraception and replacement
      therapy.

PMID- 22959549
TI  - Venous thromboembolism in neonates and children.
AB  - Thrombosis in children is gaining increased awareness, as advanced medical care
      has increased treatment intensity of hospitalized pediatric patients. Guidelines
      for diagnosis and treatment of children and neonates with venous thromboembolism
      (VTE) are mostly extrapolated from adult data, despite the uniqueness of their
      hemostatic system. Whereas inherited thrombophilia (IT) have been established as
      risk factors for VTE in adults, in children with idiopathic VTE and in pediatric
      populations in which thromboses were associated with medical diseases, IT have
      been described as additional risk factors. Follow-up data for VTE recurrence in
      children suggest a recurrence rate between 3% (neonates) and 21% (idiopathic
      VTE). Apart from underlying medical conditions, recently reported systematic
      reviews on pediatric VTE and stroke have shown significant associations between
      thrombosis and presence of factor V G1691A, factor II G20210A, protein C-,
      protein S- and antithrombin deficiency, even more pronounced when combined IT
      were involved. The pooled odds ratios (OR: single IT) for VTE onset ranged from
      2.4 for the factor II G20210A mutation (cerebrovascular occlusion) to 9.4 in
      children with antithrombin deficiency (venous VTE). In addition, the pooled OR
      for persistent antiphospholipid antibodies/lupus anticoagulants was 6.6 for
      children with cerebrovascular occlusion and 4.9 for pediatric cases with venous
      VTE. The factor II G20210A mutation (OR: 2.1), protein C- (OR: 2.4), S- (OR:
      3.1), and antithrombin deficiency (OR: 3.0) did also play a significant role at
      recurrence. Among primarily asymptomatic family members of pediatric VTE index
      cases annual VTE incidences were 2.82% (95% confidence interval [95% CI], 1.63
      4.80%) in carriers of antithrombin, protein C, or protein S-deficiency, 0.42%
      (0.12-0.53%) for factor II G202010A, 0.25% (0.12-0.53%) for factor V G1691A, and
      0.10% (0.06-0.17%) in relatives with no IT. Based on these data diagnosis,
      screening and treatment issues will be discussed.

PMID- 22959550
TI  - Travel-related thrombosis.
AB  - Travel-related thrombosis is a serious public health concern considering the
      large and increasing number of travellers. Due to a lack of evidence, counselling
      air travellers on their venous thrombosis risk is not immediately
      straightforward, and advice will have to be based mostly on theoretical grounds.
      In this review a basis for these considerations is given. First of all it needs
      to be recognized that venous thrombosis is a multicausal disease, i.e. several
      risk factors have to be present before an event occurs. This is reflected in the
      literature where clearly increased risks have been described for certain groups,
      such as subjects with factor V Leiden, those who use oral contraceptives or are
      obese. Also, an increased risk for tall and short people has been reported. So,
      for subjects with a known risk factor who plan to travel, benefits and risks of
      thrombosis prophylaxis, (pharmacological or other), need to be weighed. This
      review provides some theoretical examples. For all other travellers, the advice
      to move and exercise as much as possible is likely to be sufficient.

PMID- 22959551
TI  - The promise of novel direct oral anticoagulants.
AB  - The standard effective treatment of venous and arterial thromboembolism includes
      unfractionated and low-molecular weight heparin as well as warfarin, which have
      major disadvantages. In recent years, new anticoagulants have been developed in
      an attempt to overcome the known limitations of established treatment and develop
      improved therapies. This chapter reviews pharmacological properties of the new
      anticoagulants, the most recent trials assessing their safety and efficacy as
      well as potential advantages and disadvantages of using these novel drugs in real
      life.

PMID- 22959552
TI  - Advances in the management of venous thromboembolism.
AB  - The past decade has witnessed important advances in the diagnosis and treatment
      of venous thromboembolism with excellent opportunities to apply evidence-based
      medicine for many of the steps in the management of the disease. This review
      discusses the clinical prediction rules that should be used to reduce utilization
      of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk
      stratification for thrombolytic therapy or outpatient management of pulmonary
      embolism. The treatment options have increased and include low-molecular-weight
      heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter
      either monitored or not monitored, fondaparinux and rivaroxaban for the initial
      phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin
      inhibitors are or will soon become available. The VKAs have been subjected to
      many randomised trial addressing the initiation, intensity, monitoring and self
      management. Extended anticoagulation and the selection for that is finally
      reviewed.

PMID- 22959553
TI  - Thrombolytic therapy for submassive pulmonary embolism.
AB  - Approximately 10% of all patients with acute pulmonary embolism (PE) die within
      the first three months after diagnosis. However, PE is not universally life
      threatening, but covers a wide spectrum of clinical severity and death risk.
      Thrombolytic treatment is indicated patients with acute massive PE who are at
      high risk for early death, i.e. those patients who present with arterial
      hypotension and shock. On the other hand, low molecular-weight heparin or
      fondaparinux is adequate treatment for most normotensive patients with PE.
      Recombinant tissue plasminogen activator, given as 100 mg infusion over 2 h, is
      the treatment of choice for patients with PE, although older regimens using
      urokinase or streptokinase are also efficacious. Beyond the relatively small
      numbers of patients with massive, high-risk PE as a target population for
      thrombolysis, there is increasing awareness of the need for risk stratification
      of normotensive patients and the search for an intermediate-risk group (also
      called submassive PE). Recent meta-analyses of cohort studies suggest that
      imaging of the right ventricle or biomarkers of myocardial injury alone may be
      insufficient for guiding therapeutic decisions. Instead, accumulating evidence
      appears to support strategies which combine the information provided by an
      imaging procedure with a biomarker test. These data provide the rationale for a
      large multinational randomized trial which has set out to determine whether
      normotensive patients with right ventricular dysfunction, detected by
      echocardiography or computed tomography, plus evidence of myocardial injury as
      indicated by a positive troponin test, may benefit from early thrombolytic
      treatment. This study, which is underway in 13 European countries, will enroll a
      total of 1000 patients and will be completed in 2012. Together with a parallel
      trial currently being conducted in the United States, it will hopefully answer
      the question whether thrombolysis is indicated in submassive PE, thus terminating
      a 40-year-old debate and filling an important gap in our management concept for
      acute pulmonary embolism.

PMID- 22959554
TI  - Advances in the diagnosis and management of postthrombotic syndrome.
AB  - Postthrombotic syndrome (PTS) is a frequent long-term complication of deep vein
      thrombosis (DVT). Known risk factors include obesity, recurrent ipsilateral DVT,
      iliofemoral DVT, persistent symptoms one month after DVT diagnosis, and having
      subtherapeutic INRs greater than 50% of the time during the first few months on
      anticoagulant therapy. Other risk factors remain under investigation. The
      Villalta scale ranks the presence and severity of signs and symptoms of PTS.
      Preventive therapies include use of elastic compression stockings. Compression
      therapy is also used to treat PTS, in addition to wound care for associated
      venous ulcers, and herbal therapies for postthrombotic ulcers and edema. Though
      not well studied, there are surgical options for severe cases of PTS refractory
      to other treatments. Ongoing clinical trials should provide insight on risk
      factors, and interventions for PTS prevention and treatment. In particular, use
      of early thrombolysis for acute iliofemoral DVT to prevent PTS is currently being
      investigated.

PMID- 22959555
TI  - Pharmacodynamics of doripenem in critically ill patients with ventilator
      associated Gram-negative bacilli pneumonia.
AB  - Several pathophysiological changes in critically ill patients are important in
      determining the therapeutic success of beta-lactam antibiotics. The aim of this
      study was to assess the population pharmacokinetics and probabilities of target
      attainment (PTAs) of doripenem in patients with ventilator-associated pneumonia,
      comparing administration by 1-h and 4-h infusion. Patients were randomised into
      two groups: Group I received a 1-h infusion of 0.5 g every 8 h (q8h) for seven
      doses; and Group II received a 4-h infusion of 0.5 g q8h for seven doses. A Monte
      Carlo simulation was performed to determine the PTAs. PTAs of achieving 40%
      T(>MIC) [exposure time during which the free drug concentration remains above the
      minimum inhibitory concentration (MIC)] and 75% T(>MIC) are required for
      effective bactericidal activity of this agent in immunocompetent and
      immunocompromised hosts, respectively. Values of volume of distribution and total
      clearance of doripenem in these patients were 17.26+/-1.83 L and 24.89+/-1.63
      L/h, respectively. For pathogens with a MIC of 1 MUg/mL, the PTAs of achieving
      40% T(>MIC) following administration of doripenem by a 1-h and 4-h infusion of
      0.5 g q8h were 92.95% and 98.32%, respectively. For pathogens with a MIC of 2
      MUg/mL in immunocompromised hosts, the PTAs of achieving 80% T(>MIC) following
      administration of doripenem by 1-h and 4-h infusion of 2 g q8h were 56.57% and
      91.21%, respectively. In conclusion, these findings indicated that higher than
      recommended doses in this patient population, particularly neutropenic patients,
      would be necessary to optimise the pharmacokinetics of doripenem.

PMID- 22959556
TI  - Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1
      phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a
      highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV
      inhibitor for the treatment of type 2 diabetes.
AB  - Dipeptidyl peptidase IV (DPP-4) inhibition is suitable mechanism for once daily
      oral dosing regimen because of its low risk of hypoglycemia. We explored linked
      bicyclic heteroarylpiperazines substituted at the gamma-position of the proline
      structure in the course of the investigation of l-prolylthiazolidines. The
      efforts led to the discovery of a highly potent, selective, long-lasting and
      orally active DPP-4 inhibitor, 3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5
      yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine (8 g), which has a unique
      structure characterized by five consecutive rings. An X-ray co-crystal structure
      of 8 g in DPP-4 demonstrated that the key interaction between the phenyl ring on
      the pyrazole and the S(2) extensive subsite of DPP-4 not only boosted potency,
      but also increased selectivity. Compound 8 g, at 0.03 mg/kg or higher doses,
      significantly inhibited the increase of plasma glucose levels after an oral
      glucose load in Zucker fatty rats. Compound 8 g (teneligliptin) has been approved
      for the treatment of type 2 diabetes in Japan.

PMID- 22959557
TI  - Comparison of local anesthetic effects of lidocaine versus tramadol and effect of
      child anxiety on pain level in circumcision procedure.
AB  - OBJECTIVE: To compare the local anesthetic effects of tramadol hydrochloride with
      those of lidocaine in circumcision procedures. We also investigated the effect of
      child anxiety on pain level. PATIENTS AND METHODS: A total of 70 children were
      included in this study. The children were randomized into 3 groups. Group 1 (n =
      26) received lidocaine hydrochloride + epinephrine and they underwent
      circumcision using Ali's clamp((r)). Group 2 (n = 35) received lidocaine
      hydrochloride + epinephrine and group 3 (n = 12) 5% tramadol. The last two groups
      underwent conventional circumcision. RESULTS: The mean anxiety score was 22.6. We
      did not find significant differences in terms of anxiety score among the groups
      (p = 0.761). When the pain scores of the groups during injection were compared,
      it was found that there were no significant differences. However, the pain score
      of the third group was significantly high when it was compared with the first and
      second group 2 and 10 min after injection. In the correlation analysis, we found
      a positive correlation between children's anxiety scores and the pain degree
      during injection (r = 0.373, p = 0.001). CONCLUSION: Tramadol may not provide
      effective local anesthesia in male circumcision. The child's anxiety before the
      circumcision seems to have a negative effect on pain level.

PMID- 22959558
TI  - Realization of cavitation fields based on the acoustic resonance modes in an
      immersion-type sonochemical reactor.
AB  - Different modes of cavitation zones in an immersion-type sonochemical reactor
      have been realized based on the concept of acoustic resonance fields. The reactor
      contains three main components, namely a Langevin-type piezoelectric transducer
      (20 kHz), a metal horn, and a circular cylindrical sonicated cell filled with tap
      water. In order to diminish the generation of cavitation bubbles near the horn
      tip, an enlarged cone-shaped horn is designed to reduce the ultrasonic intensity
      at the irradiating surface and to get better distribution of energy in the
      sonicated cell. It is demonstrated both numerically and experimentally that the
      cell geometry and the horn position have prominent effects on the pressure
      distribution of the ultrasound in the cell. With appropriate choices of these
      parameters, the whole reactor works at a resonant state. Several acoustic
      resonance modes observed in the simulation are realized experimentally to
      generate a large volume of cavitation zones using a very low ultrasonic power.

PMID- 22959559
TI  - Effect of stage duration on maximal heart rate and post-exercise blood lactate
      concentration during incremental treadmill tests.
AB  - OBJECTIVES: This study compared the responses during maximal incremental
      treadmill tests of 1-min, 2-min, and 3-min stage durations mainly in terms of
      maximal heart rate (HRmax) and peak blood lactate concentration (LApeak). DESIGN:
      Repeated-measures. METHODS: Thirty-four male, recreational, endurance-trained
      runners (40+/-13 years) performed three tests on a motorized treadmill. The tests
      started at 8kmh(-1) with increments of 1kmh(-1) every 1min for the short-stage
      protocol, every 2min for the intermediate-stage protocol, and every 3min for the
      long-stage protocol. LApeak was defined for each subject as the highest value
      among the lactate concentrations determined at the end of each test and at the
      third, fifth and seventh minutes after test, during passive recovery. RESULTS:
      Analysis of variance revealed a significant effect of the stage duration on the
      HRmax (p=0.003) and LApeak (p=0.001). The HRmax was higher in the intermediate
      stage compared to the short-stage protocol (184.8+/-12.7 vs. 181.8+/
      12.1beatsmin(-1), p<0.001), but no significant differences were found between the
      long-stage (183.1+/-12.1beatsmin(-1)) and the intermediate-stage or short-stage
      protocols (p>0.05). The LApeak was lower in the long-stage compared to the short
      stage and intermediate-stage protocols (7.9+/-2.2 vs. 9.4+/-2.2 and 9.2+/
      1.9mmolL(-1), respectively, p<0.05). Further, blood lactate reached peak
      concentration at the fifth minute after test for all the protocols. CONCLUSIONS:
      Thus, HRmax and LApeak depend on the stage duration of the incremental test, but
      the moment at which blood lactate reaches peak concentration is independent of
      the duration. Further, we suggest 2-min stage duration protocols to determine
      HRmax.

PMID- 22959560
TI  - Ozone inactivation of resistant microorganisms: Laboratory analysis and
      evaluation of the efficiency of plants.
AB  - In this work, the ozone inactivation of resistant microorganisms is studied and a
      method to assess the efficiency of a drinking water plant to inactivate resistant
      microorganisms using ozone is proposed. This method aims at computing the
      fraction of resistant microorganisms that are not inactivated at the exit of an
      ozonation step by evaluating the duration of the lag phase of the ozone
      inactivation of these microorganisms and the contact time distribution of these
      microorganisms with the ozone in the step. To evaluate the duration of the lag
      phase of the ozone inactivation of resistant pathogenic microorganisms, an
      experimental procedure is proposed and applied to Bacillus subtilis spores. The
      procedure aims at characterizing the ozone inactivation kinetics of B. subtilis
      spores for different temperature and ozone concentration conditions. From
      experimental data, a model of the ozone inactivation of B. subtilis spores is
      built. One of the parameters of this model is called the lag time and it measures
      the duration of the lag phase of the ozone inactivation of B. subtilis spores.
      This lag time is identified for different temperature and ozone concentration
      conditions in order to establish a correlation between this lag time and the
      temperature and ozone concentration conditions. To evaluate the contact time
      distribution between microorganisms and the ozone in a disinfection step of a
      drinking water plant, a computational fluid dynamics tool is used. The proposed
      method is applied to the ozonation channel of an existing drinking water plant
      located in Belgium and operated by Vivaqua. Results show that lag times and
      contact times are both in the same order of magnitude of a few minutes. For a
      large range of temperatures and ozone concentrations in the Tailfer ozonation
      channel and for the highest hydraulic flow rate applied, a significant fraction
      of resistant microorganisms similar to B. subtilis spores is not inactivated.

PMID- 22959561
TI  - Prolonged swing phase rectus femoris activity is not associated with stiff-knee
      gait in children with cerebral palsy: a retrospective study of 407 limbs.
AB  - Prolonged swing phase rectus femoris (RF) activity has been implicated as a cause
      of stiff-knee gait (SKG) in children with cerebral palsy (CP) and continues to be
      cited as an indicator for RF intervention. The purpose of this study was to
      determine what, if any, association exists between abnormal RF activity during
      preswing, initial swing and/or midswing and SKG in children with CP. This
      retrospective analysis involved three examiners independently reviewing sagittal
      plane knee kinematic and RF surface electromyographic (EMG) data from 407
      affected limbs of 234 pediatric patients with CP. Five kinematic parameters were
      rated by each examiner as normal or pathologic: peak knee flexion, knee range of
      motion during initial swing, total knee range of motion, peak knee flexion
      timing, and rate of knee flexion. These ratings were used to classify each limb
      into one of three groups: SKG, Borderline SKG, or Non-SKG. From a representative
      EMG tracing, RF activity was examined during: the first half of preswing, the
      latter 2/3 of initial swing, and midswing. Chi-squared tests were used to
      determine if significant associations existed between SKG and RF activation
      during these three subphases. There was no association between SKG and prolonged
      RF activity during the latter 2/3 of initial swing or during midswing. However, a
      significant relationship between SKG and RF activity during the first half of
      preswing was found (p<0.001). Neither prolonged RF activity during initial swing,
      nor the presence of RF activity during midswing, were associated with SKG, thus
      refuting these commonly held associations.

PMID- 22959562
TI  - A single-sample microarray normalization method to facilitate personalized
      medicine workflows.
AB  - Gene-expression microarrays allow researchers to characterize biological
      phenomena in a high-throughput fashion but are subject to technological biases
      and inevitable variabilities that arise during sample collection and processing.
      Normalization techniques aim to correct such biases. Most existing methods
      require multiple samples to be processed in aggregate; consequently, each
      sample's output is influenced by other samples processed jointly. However, in
      personalized-medicine workflows, samples may arrive serially, so renormalizing
      all samples upon each new arrival would be impractical. We have developed Single
      Channel Array Normalization (SCAN), a single-sample technique that models the
      effects of probe-nucleotide composition on fluorescence intensity and corrects
      for such effects, dramatically increasing the signal-to-noise ratio within
      individual samples while decreasing variation across samples. In various
      benchmark comparisons, we show that SCAN performs as well as or better than
      competing methods yet has no dependence on external reference samples and can be
      applied to any single-channel microarray platform.

PMID- 22959563
TI  - Incidence of sternal wound infection after reexploration in the intensive care
      unit and the use of local gentamycin.
AB  - BACKGROUND: Reoperation for bleeding is a known emergency complication after
      cardiac operations. When performed in the intensive care unit (ICU), sterility
      issues arise. Our aim was to examine the incidence of sternal wound infection
      (SWI) after reexploration in the ICU for bleeding with routine use of local
      gentamycin. METHODS: From January 2003 until December 2009, 4,863 patients
      underwent cardiac operations through a median sternotomy at our institution. We
      conducted a retrospective database review identifying all patients who required
      reoperations. The occurrence of SWI in this group was compared with the general
      cardiac surgical population. Reoperations for bleeding during this period were
      conducted routinely in the ICU with prophylactic application of a gentamycin
      sponge between the sternal halves before closure in all cases. RESULTS:
      Reexploration for bleeding was necessary in 302 patients (6.2%), and SWI occurred
      in 11, for a rate of 3.6%. SWI occurred in 174 of the 4,561 non-reexplored
      patients, for a similar rate of 3.8% (p>0.9). These values are similar to our
      overall rate of SWI of 3.8% (n=185) in the total cohort of 4,863 patients.
      CONCLUSIONS: The incidence of SWI was not increased in our study group after
      emergency reoperation for bleeding in the ICU after the local use of gentamycin.
      Our data suggest that reexploration in an ICU setting for bleeding does not pose
      a sterility challenge and that life-threatening delays due to transfer to the
      operating theater may be avoided.

PMID- 22959564
TI  - The surgical treatment of concomitant atrial arrhythmias during redo cardiac
      operations.
AB  - BACKGROUND: With improving surgical care yielding better outcomes, patients who
      have undergone a cardiac operation are surviving longer, and surgeons will
      inevitably face an increasing number of reoperative procedures. There are few
      data reporting risk and outcome for patients undergoing atrial fibrillation
      ablation in this clinical setting. METHODS: From January 1994 through May 2009,
      we performed surgery for AF in 245 patients (134 female) who have had at least1
      prior cardiac operation. Median age was 45 years (range 1 to 75 years) and
      preoperative atrial fibrillation was paroxysmal in 161 patients (66%). Most
      common cardiac diagnoses included Ebstein anomaly (n=43), tetralogy of Fallot
      (n=36), and acquired valvular or ischemic heart disease (n=35). Median prior
      sternotomies was 1 (range 1 to 6). RESULTS: Ablative lesions most commonly
      included isolated right-sided maze (n=123; cryothermy in 84, cut and sew in 39),
      biatrial maze (n=52; cryothermy in 26, cut and sew in 26), and right atrial
      isthmus ablation (n=41; isolated in 30, concomitant in 11). There were 14 early
      deaths (5.7%). New permanent pacemaker was required in 39 patients (18%);
      indication was complete heart block in 9. Rhythm at late follow-up (median: 4.1
      years, maximum: 17.2 years) was 89% in the setting of congenital heart disease
      and 78% in acquired heart disease. CONCLUSIONS: Atrial fibrillation is common
      with a variety of pathologies requiring redo cardiac surgery. Lesion set and
      energy source are dependent on primary procedure. Concomitant AF ablation during
      redo cardiac reoperations can be performed with reasonable safety and success.

PMID- 22959565
TI  - Approaching a paradigm shift: endoscopic ablation of lone atrial fibrillation on
      the beating heart.
AB  - BACKGROUND: Percutaneous catheter ablation has been the preferred treatment
      strategy for many patients with symptomatic drug-refractory atrial fibrillation
      (AF). However, incomplete ablation lines and varying success rates remain a
      problem in certain subgroups. This article evaluates the feasibility and efficacy
      of endoscopically performed left atrial ablation in patients with lone AF.
      METHODS: Epicardial bipolar radiofrequency ablation was performed on the beating
      heart through a bilateral endoscopic approach in 89 consecutive patients with
      lone AF. This included isolation of the pulmonary veins using a clamp; isolation
      of the posterior left atrial wall, including a trigonal line to the aortic
      noncoronary sinus using a linear ablation device; and resection of the left
      atrial appendage (LAA). Preoperative, perioperative, and postoperative data were
      collected prospectively and included questionnaires and 24-hour Holter monitoring
      at 6 and 12 months and annually thereafter. RESULTS: Mean follow-up was 12+/-6
      months (range, 4-28 months). No patients were lost to follow-up. Mean duration of
      AF was 6.4+/-5.7 years, with 35% paroxysmal AF and 65% persistent or long
      standing persistent AF. Mean operation time was 180+/-43 minutes. There were no
      deaths, no conversion to sternotomy, and no early or late stroke. Freedom from AF
      was 88%, 90%, and 90% at 6, 12, and 24 months, respectively. Freedom from AF
      without antiarrhythmic drugs was 71%, 82%, and 90% at 6, 12, and 24 months,
      respectively. CONCLUSIONS: Endoscopic radiofrequency ablation on the beating
      heart reveals high success rates with low procedure-related morbidity. For
      improvement of future treatment strategies, a randomized trial is advisable to
      compare this procedure with catheter ablation in certain patient subgroups.

PMID- 22959567
TI  - Characteristics and prognostic value of lymphatic and blood vascular
      microinvasion in lung cancer.
AB  - BACKGROUND: The prognostic value of vascular microinvasion (VMI) in non-small
      cell lung cancer (NSCLC) has been a matter of discussion in recent decades. The
      last T N M classification does not take VMI into account, but many points remain
      questionable. METHODS: A retrospective study was performed of patients undergoing
      operations for NSCLC during a 20-year period. Lymphatic VMI (LVMI) was classified
      as group (G) 1, blood VMI (BVMI) as G2, LVMI and BVMI as G3, and no VMI as G4.
      The demographic, pathologic, T N M characteristics, and long-term survival of
      each group were analyzed. RESULTS: A total of 3,868 patients (G1, 334; G2, 642;
      G3, 172; G4, 2,720), mean age 61.9 +/- 10.1 years, underwent different types of
      resection, with complete lymphadenectomy in 88.5%. Adenocarcinomas were more
      frequent in G1 and G3, and squamous cell carcinomas in G2. In G2, more N1 tumors
      needed more extensive resections. G1 was equally distributed regardless of tumor
      size, but G2 prevalence increased with augmenting size. Nodules in the same lobe
      were significantly more frequent in LVMI than in BVMI. After exclusion of
      patients with R1 and R2 resections, multivariate analysis confirmed that LVMI and
      BVMI were independent prognostic factors as well as age, sex, type of resection,
      T extension, and N involvement. CONCLUSIONS: VMI is generally associated with a
      poorer prognosis. LVMI is less frequent than BVMI but has lower survival rates.
      The benefit of adjuvant therapy in VMI patients needs to be evaluated.

PMID- 22959566
TI  - In-parallel attachment of a low-resistance compliant thoracic artificial lung
      under rest and simulated exercise.
AB  - BACKGROUND: Previous thoracic artificial lungs (TALs) had blood flow impedance
      greater than that of the natural lungs, which could cause abnormal pulmonary
      hemodynamics. New compliant TALs (cTALs), however, have an impedance lower than
      that of the natural lung. METHODS: In this study, a cTAL of new design was
      attached between the pulmonary artery (PA) and the left atrium (LA) in 5 sheep
      (60.2 +/- 1.9 kg). A distal PA band was placed to control the percentage of
      cardiac output (CO) routed to the cTAL. Rest and exercise conditions were
      simulated using a continuous dobutamine infusion of 0 and 5 MUg/kg/min,
      respectively. At each dose, a hemodynamic data set was acquired at baseline (no
      flow to the cTAL), and 60%, 75%, and 90% of CO was shunted to the cTAL. RESULTS:
      Device resistance did not vary with blood flow rate, averaging 0.51 +/- 0.03 mm
      Hg/(L/min). Under all conditions, CO was not significantly different from
      baseline. Pulmonary system impedance increased above baseline only with 5
      MUg/kg/min of dobutamine and 90% of CO diverted to the cTAL. CONCLUSIONS: Results
      indicated minimal changes in pulmonary hemodynamics during PA-LA cTAL attachment
      for high device flows under rest and exercise conditions.

PMID- 22959568
TI  - Costs of transcatheter versus surgical aortic valve replacement in intermediate
      risk patients.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) offers a new treatment
      option for patients with aortic stenosis, but costs may play a decisive role in
      decision making. Current studies are evaluating TAVR in an intermediate-risk
      population. We assessed the in-hospital and 1-year follow-up costs of patients
      undergoing TAVR and surgical aortic valve replacement (SAVR) at intermediate
      operative risk and identified important cost components. METHODS: We
      prospectively collected clinical data on 141 patients undergoing TAVR and 405
      undergoing SAVR. Propensity score matching yielded 42 matched pairs at
      intermediate risk. Costs were assessed using a detailed resource-use approach and
      compared using bootstrap methods. RESULTS: In-hospital costs were higher in TAVR
      patients than in SAVR patients (?40802 vs ?33354, respectively; p=0.010). The
      total costs at 1 year were ?46217 vs ?35511, respectively (p=0.009). The TAVR was
      less costly with regard to blood products, operating room use, and length-of
      stay. CONCLUSIONS: For intermediate-risk patients with severe aortic stenosis the
      costs at 1 year are higher for TAVR than for SAVR. The difference was mainly
      caused by the higher costs of the transcatheter valve and was not compensated by
      the lower costs for blood products and hospital stay in TAVR patients. Therefore,
      SAVR remains a clinically and economically attractive treatment option.

PMID- 22959569
TI  - Reoperative sternotomy is associated with increased mortality after heart
      transplantation.
AB  - BACKGROUND: Although several studies have examined factors affecting survival
      after orthotopic heart transplantation (OHT), few have evaluated the impact of
      reoperative sternotomy. We undertook this study to examine the incidence and
      impact of repeat sternotomies on OHT outcomes. METHODS: We conducted a
      retrospective review of all adult OHT from 2 institutions. Primary stratification
      was by the number of prior sternotomies. The primary outcome was survival.
      Secondary outcomes included blood product utilization and commonly encountered
      postoperative complications. Multivariable Cox proportional hazards regression
      models examined mortality while linear regression models examined blood
      utilization. RESULTS: From January 1995 to October 2011, 631 OHT were performed.
      Of these, 25 (4.0%) were redo OHT and 182 (28.8%) were bridged to transplant with
      a ventricular assist device; 356 (56.4%) had undergone at least 1 prior
      sternotomy. On unadjusted analysis, reoperative sternotomy was associated with
      decreased 90-day (98.5% vs 90.2%, p<0.001), 1-year (93.1% vs 79.6%, p<0.001), and
      5-year (80.4% vs 70.1%, p=0.002) survival. This difference persisted on
      multivariable analysis at 90 days (hazard ratio [HR] 2.99, p=0.01), 1 year (HR
      2.98, p=0.002), and 5 years (HR 1.62, p=0.049). The impact of an increasing
      number of prior sternotomies was negligible. On multivariable analysis, an
      increasing number of prior sternotomies was associated with increased
      intraoperative blood product utilization. Increasing blood utilization was
      associated with decreased 90-day, 1-year, and 5-year survival. CONCLUSIONS:
      Reoperative sternotomy is associated with increased mortality and blood
      utilization after OHT. Patients with more than 1 prior sternotomy do not
      experience additional increased mortality. Carefully selected patients with
      multiple prior sternotomies have decreased but acceptable outcomes.

PMID- 22959570
TI  - Initial experience with the use of biological implants for soft tissue and chest
      wall reconstruction in thoracic surgery.
AB  - BACKGROUND: Synthetic materials have traditionally been used for tissue
      reconstruction in thoracic surgery. New biomaterials have been tested in other
      areas of surgery with good results. The aim of our study is to evaluate our
      initial experience using prostheses in extended thoracic surgery. METHODS: A
      review was performed of all patients who underwent extended surgical procedures
      requiring soft tissue reconstruction with bioprosthetic materials after thoracic
      surgery from August 2009 to August 2011. A total of 44 consecutive patients were
      included. Operations involved radical pleurectomy and decortication for
      mesothelioma (n = 29), extended operations for thoracic malignancies (n = 8),
      surgery for trauma or perforated organs or complications (n = 6), and for benign
      infectious causes (n = 1). RESULTS: A total of 76 patches were used in 44
      patients (median of 2; range 1 to 3 per patient). Median hospital stay was 13
      (range 5 to 149) days. Three patients died during the postoperative period
      (6.8%); pulmonary embolism 5 days after intrapericardial pneumonectomy with chest
      wall reconstruction, fatal pneumonia 26 days after radical pleurectomy and
      decortication for mesothelioma, and bronchopleural fistula 11 days after
      pneumonectomy with diaphragm and atrium excision for lung cancer after initial
      chemoradiotherapy. No other surgical exploration or removal of patches has been
      required for infection. CONCLUSIONS: Our initial experience of using
      bioprosthetic patches for soft tissue reconstruction in thoracic surgery has
      proven satisfactory with overall acceptable results. The infection rates are low
      even when a proportion of procedures were performed under contaminated
      environments. Biologic prosthesis should be part of the surgical options to
      reconstruct soft tissues in thoracic surgery.

PMID- 22959571
TI  - Lactate clearance time and concentration linked to morbidity and death in cardiac
      surgical patients.
AB  - BACKGROUND: Early predictors of morbidity after cardiac operations are lacking.
      Elevated lactate concentrations in the immediate postoperative period reflect
      unmet metabolic demand and may be associated with outcome. This study examined
      the association between early plasma lactate concentrations and outcome after
      cardiac operations. METHODS: As a retrospective cohort investigation, patient
      information was obtained from the Cardiovascular Information and the
      Anesthesiology Institute's patient registries. Inclusion criteria were all adult
      cardiac surgical patients undergoing isolated coronary artery bypass grafting or
      valve procedures, or coronary artery bypass grafting with a valve procedure, from
      January 1, 2008, to August 7, 2008 (arterial lactate values were added to the
      patient registry beginning January 1, 2008). RESULTS: Lactate concentrations
      during the initial 12 postoperative hours of a patient's stay in the
      cardiovascular intensive care unit were averaged (mean lactate concentration),
      and linear regression concentrations over time were used to predict when the
      lactate concentration would reach 1.5 mmol/L in individual patients (predicted
      lactate clearance time). We also considered the product of the mean and clearance
      (product value). Predicted lactate clearance time, mean lactate concentration,
      and product value were associated with any type of reoperation, death, and a set
      of composite outcomes (p < 0.001 for each). The accuracy of these indices was
      moderate to good, with the highest C statistic (for product value) being 0.82.
      CONCLUSIONS: Predicted lactate clearance time, mean lactate concentration, and
      product value are each associated with death, any type of reoperation, and a set
      of composite outcomes in patients undergoing coronary artery bypass grafting or
      valve operations, or both. Product value provided the best early prognostic
      guidance in individual patients.

PMID- 22959572
TI  - Predictors for early and late outcomes after coronary artery bypass grafting in
      hemodialysis patients.
AB  - BACKGROUND: Markedly higher hospital and long-term mortality after coronary
      artery bypass grafting (CABG) have been reported in hemodialysis (HD)-dependent
      patients. We tried to identify the predictors for short-term and long-term
      outcomes after CABG, which have not been well studied. METHODS: Between 1993 and
      2010, 152 patients undergoing HD (117 men; HD duration of 8.7+/-8.0 years)
      underwent isolated CABG. Our strategies included use of a single internal
      thoracic artery (ITA) in patients with diabetes mellitus (DM), bilateral ITAs in
      patients without DM, and possible avoidance of cardiopulmonary bypass (CPB) after
      2003. RESULTS: Thirty-six percent of patients underwent conventional CABG: 20%
      had on-pump beating heart procedures and 44% had off-pump procedures, with 2.8+/
      1.0 anastomoses. Hospital mortality was 10.6% with improvement to 6.8% after
      2003. Predictors for hospital death were left ventricular ejection fraction
      (LVEF) less than 0.40 (p=0.042), use of CPB (p=0.046), and postoperative need for
      continuous hemofiltration (p=0.037). After follow-up of 49+/-42 months, the
      overall survival rates were 76.9%, 60.0%, 43.9%, and 36.2% and the cardiac events
      free rates were 77.0%, 70.1%, 55.9%, and 44.8% at 3, 5, 8, and 10 years,
      respectively, in the Kaplan-Meier model. A multivariate Cox proportional hazard
      model identified age older than 63 years (p=0.014), DM (p=0.036), and peripheral
      artery disease (PAD) (p=0.044) as predictors for late death, and DM (p=0.038) and
      LVEF less than 0.40 (p=0.027) as predictors for late cardiac events. CONCLUSIONS:
      Although early outcomes have been improved by off-pump techniques, late outcomes
      are not satisfactory in patients who rely on HD and undergo CABG. To improve late
      outcomes we may need aggressive management of DM, PAD, and low LVEF in those
      patients.

PMID- 22959573
TI  - Risk of valve-related events after aortic valve repair.
AB  - BACKGROUND: The impetus for aortic valve (AV) repair is to decrease valve-related
      complications in comparison to prosthetic valve replacement. However, relatively
      few data are available to confirm this hypothesis. We analyzed valve-related
      complications in a large series of patients undergoing AV repair. METHODS:
      Between 1995 and 2010, 475 patients underwent elective AV repair for aortic
      insufficiency or aortic aneurysm. The mean age was 53 years, and 81% were male.
      Valve-related outcomes were defined as per published guidelines. Survival and
      freedom from valve-related events were reported using the Kaplan-Meier method and
      linearized event rates. Clinical follow-up was 98.3% complete with a mean follow
      up time of 4.6 years. RESULTS: Thirty-day mortality was 0.8% (n = 4). At 10
      years, overall survival was 73% +/- 5%, freedom from cardiac death was 81% +/-
      4%, and freedom from valve-related death was 90% +/- 3%. Freedom from significant
      aortic insufficiency was 84% +/- 3%. A total of 28 patients needed early (n = 7)
      or late (n = 21) AV reoperation; all of them survived reoperation, and 8 had
      repeat repair. Ten-year freedom from AV reoperation was 86% +/- 3%, and freedom
      from AV replacement was 90% +/- 3%. Freedom from AV reoperation was similar in
      tricuspid and bicuspid valve. During the follow-up period, linearized rate of
      thromboembolic event, bleeding, and AV endocarditis was 1.1%, 0.23%, and 0.19%
      per year, respectively. Ten-year freedom from valve-related events including AV
      reoperation, thromboembolic event, bleeding, and endocarditis was 74% +/- 3%.
      CONCLUSIONS: The current findings confirm that AV repair is associated with low
      mortality, acceptable durability, and a low risk of valve-related events.

PMID- 22959574
TI  - Cerebral and somatic oxygen saturations after repair of tetralogy of Fallot:
      effects of extubation on regional blood flow.
AB  - BACKGROUND: After repair of tetralogy of Fallot, some patients experience a low
      cardiac output state owing to right ventricular diastolic failure. Negative
      pressure ventilation has been shown to improve cardiac output in these patients.
      What has not been evaluated is the effect of extubation and loading of the
      respiratory muscles on the distribution of cardiac output after repair of
      tetralogy of Fallot. METHODS: In 23 consecutive patients undergoing repair of
      tetralogy of Fallot, standard hemodynamic variables, central venous oxygen
      saturations, and near infrared spectroscopy of the brain, mesenteric, and renal
      circulations were monitored for 30 minutes before and after extubation. RESULTS:
      With extubation, the systolic blood pressure increased significantly from 96 +/-
      11 to 106 +/- 15 mm Hg (p = 0.002) while the heart rate remained unchanged. With
      extubation, the central venous oxygen saturation increased significantly from 65%
      +/- 7% to 70% +/- 10% (p = 0.003). Cerebral oxygen saturations increased
      significantly from 67% +/- 10% to 72% +/- 9% (p = 0.0001), whereas mesenteric
      oxygenation fell significantly from 74% +/- 15% to 72% +/- 15% (p = 0.04). Renal
      oxygenation was unaffected by extubation. CONCLUSIONS: Cardiac output and
      cerebral oxygenation increased significantly during spontaneous respiration, the
      latter suggesting that the brain was in or approaching an oxygen supply-dependent
      state before extubation. Despite the increase in cardiac output, the presumed
      increase in respiratory pump perfusion, as well as the concurrent increase in
      cerebral perfusion, came at the expense of mesenteric perfusion. Renal
      oxygenation remained unchanged with extubation.

PMID- 22959575
TI  - Vibration response imaging in prediction of pulmonary function after pulmonary
      resection.
AB  - BACKGROUND: Vibration response imaging (VRI) is a new technique that captures
      lung sounds generated by the flow of air through the lungs. It predicts
      postoperative values for an intended lung resection. In this study, we measured
      the predicted postoperative pulmonary function as determined by a perfusion lung
      scan and the VRI, and compared with results from the postoperative pulmonary
      function. METHODS: This study was performed prospectively in patients who were
      candidates for major pulmonary resection. Each patient underwent a pulmonary
      function test, perfusion scintigraphy, and VRI within 1 week before operation.
      Postoperative lung function was measured at 4 to 6 weeks. RESULTS: The study
      enrolled 44 patients. There were no significant differences for predicted
      postoperative forced expiratory volume in 1 second (ppoFEV(1)) and predicted
      postoperative diffusion capacity of the lung for carbon monoxide (ppoDlco)
      between scan and VRI. Both ppoFEV(1) and ppoDlco using a scan and VRI predicted
      the postoperative results well, respectively. The postoperative FEV(1) was
      correlated with ppoFEV(1) using a scan (r = 0.83, p < 0.001), and the ppoFEV(1)
      using a VRI (r = 0.83, p < 0.001). The postoperative Dlco was correlated with the
      ppoDlco using a scan (r = 0.85, p < 0.001), and the ppoDlco using a VRI (r =
      0.80, p < 0.001). CONCLUSIONS: The VRI was highly predictive of postoperative
      FEV(1) and Dlco for lung resection.

PMID- 22959576
TI  - Tranexamic Acid in on-pump coronary artery bypass grafting without clopidogrel
      and aspirin cessation: randomized trial and 1-year follow-up.
AB  - BACKGROUND: Dual antiplatelet therapy is widely used in patients with coronary
      artery disease and increases the risk of excessive bleeding and transfusion in
      those undergoing coronary artery bypass grafting (CABG). METHODS: The study was a
      prospective, randomized, double-blinded and placebo-controlled trial. Patients
      undergoing primary and isolated on-pump CABG with their last dose of clopidogrel
      and aspirin less than 7 days preoperatively were randomly assigned to receive
      tranexamic acid (15 mg/kg before surgical incision and 15 mg/kg after protamine
      neutralization) or a corresponding volume of saline solution. The primary outcome
      was allogeneic erythrocyte transfusion. RESULTS: Randomly assigned participants
      were 120 adults among whom 117 were analyzed, 58 in the tranexamic acid group and
      59 in the placebo group. As compared with placebo, tranexamic acid reduced
      allogeneic erythrocyte requirement-both the volume transfused (4.84 +/- 5.85
      versus 9.36 +/- 11.41 units; mean difference -4.52 units; 95% interval confidence
      [CI], -7.85 to -1.19 units; p < 0.001) and the ratio exposed (72.4% versus 91.5%;
      risk difference in percentage point, -19.1; 95% CI, -32.6 to -5.59; relative
      risk, 0.79; 95% CI, 0.66 to 0.94; p = 0.007)-blood loss (1069.1 +/- 565.5 mL
      versus 1449.8 +/- 899.8 mL; mean difference, -380.7 mL; 95% CI, -656.4 to -104.9
      mL; p = 0.005), major bleeding (50.0% versus 78.0%; risk difference, -28.0; 95%
      CI, -44.6 to -11.3; relative risk, 0.64; 95% CI, 0.48 to 0.86; p = 0.002), and
      reoperation (0.0% versus 10.2%; risk difference, -10.2; 95% CI, -17.9 to -2.46;
      relative risk, 0.08; 95% CI, 0.00 to 1.36; p = 0.01). CONCLUSIONS: Tranexamic
      acid significantly reduced blood loss, major bleeding, reoperation, and
      allogeneic transfusion in patients undergoing primary and isolated on-pump CABG
      without clopidogrel and aspirin cessation.

PMID- 22959577
TI  - Salvage esophagectomy for locoregional failure after chemoradiotherapy in
      patients with advanced esophageal cancer.
AB  - BACKGROUND: Definitive chemoradiotherapy is associated with high local treatment
      failure rates, and surgical resection may be an appropriate salvage therapy.
      However, the efficacy and safety of salvage esophagectomy have not been
      elucidated fully. The clinical outcomes of salvage esophagectomy for locoregional
      failure after chemoradiotherapy were assessed. METHODS: Twelve patients who
      underwent salvage esophagectomy after chemoradiotherapy between January 2003 and
      November 2010 were included in this retrospective analysis. Baseline demographics
      and survivals of these patients were compared with 21 patients who did not
      receive salvage esophagectomy for locoregional failure only after
      chemoradiotherapy, identified from our own previous prospective trials. RESULTS:
      The median age was 62.5 years (range 50 to 69) and all patients had squamous cell
      carcinoma. The median radiation dose was 54.0 Gy (range 41.4 to 66.0) and the
      median interval between completion of chemoradiation and surgery was 8.0 months
      (range 2.0 to 32.9). There were no in-hospital deaths. Pulmonary complication was
      the most common postoperative morbidity (42%), and anastomotic leakage occurred
      in 1 patient (8%). With a median follow-up period of 29.3 months (range 5.8 to
      73.0), the overall 3-year survival rate was 58%. Patients with early pathologic
      stage disease (T1/2 and N0) showed significantly prolonged survival (p=0.03)
      compared with those with advanced pathologic stage (T3/T4 or N1). Patients with
      salvage esophagectomy had prolonged event-free survival and overall survival
      compared with those patients with locoregional failure who received primary
      chemotherapy or boost radiotherapy (p<0.001). CONCLUSIONS: While salvage
      esophagectomy for locoregional failure after chemoradiotherapy should be employed
      with great caution, it appears to be a feasible and effective therapeutic option
      for highly selected patients, especially with early pathologic stage disease.
      Salvage esophagectomy can be recommended as the only current curative treatment
      option for patients with locoregional failure after chemoradiotherapy.

PMID- 22959578
TI  - Isolated reoperative minimally invasive tricuspid valve operations.
AB  - BACKGROUND: Tricuspid valve (TV) regurgitation has recently been identified as a
      major risk factor for long-term mortality. Isolated reoperative tricuspid valve
      repair/replacement (TVR/r) carries an excessively high operative risk. Currently,
      isolated TVR/r with minimally invasive access through a right lateral thoracotomy
      is being used increasingly in our institution to treat progressive TV pathologic
      processes after previous cardiac operations. We analyzed our early and midterm
      results with reoperative TVR/r in this unique patient cohort. METHODS: Forty
      eight consecutive patients underwent isolated TV operations after previous
      cardiac operations with minimally invasive access through a right lateral
      thoracotomy at our institution between September 2000 and December 2011. Previous
      cardiac operations included 26 patients (54.2%) with mitral valve
      replacement/repair, 18 patients (37.5%) with an aortic valve replacement, 10
      patients (20.4%) with a TVR/r, and 8 patients (16.7%) with coronary artery bypass
      grafting. Operations were performed electively in 79% of patients (n=38). Mean
      patient age was 63.8+/-13.4 years, with an average log EuroSCORE of 13.9%+/
      11.3%; 67% of patients were women. Follow-up was 94% complete, with a mean
      duration of 2.8+/-2.3 years. RESULTS: Thirty-day mortality for patients
      undergoing elective surgery was zero. For all patients early mortality was 4.2%.
      Five-year survival for patients after elective reoperative TVR/r through
      minimally invasive access was 72.2%+/-10.0%, and 5-year freedom from TV-related
      reoperations was 88.1%+/-6.7%, respectively. CONCLUSIONS: Minimally invasive
      access through a right thoracotomy provides a safe option for reoperative TVR and
      offers excellent early outcome, particularly in elective cases. Surgical
      intervention should be performed earlier rather than later.

PMID- 22959579
TI  - Impact of pulmonary valve replacement in tetralogy of Fallot with pulmonary
      regurgitation: a comparison of intervention and nonintervention.
AB  - BACKGROUND: The timing and indicators for surgical pulmonary valve replacement
      (PVR) in patients with pulmonary regurgitation (PR) after repair of tetralogy of
      Fallot (ToF) are controversial. In this study we tested the hypothesis that
      delaying PVR in patients with ToF and severe PR would lead to short-term
      progressive deterioration in right ventricular/left ventricular (RV/LV)
      dimensions or function. We compared PVR-treated patients with matched untreated
      patients who were eligible for PVR based on hemodynamic status. METHODS: A
      current cohort of 87 patients with ToF and free PR serial cardiovascular magnetic
      resonance (CMR) assessments at a median interval of 1.8 years (interquartile
      range [IQR], 1.4-2.1) were identified. During this interval, 51 patients had
      surgical PVR and 36 patients were managed conservatively. Twenty-five patients
      from each group were matched for comparison using propensity score matching
      (PSM). RV and LV measurements were assessed by CMR at rest at follow-up. RESULTS:
      There was no significant deterioration in RV or LV measurements in the matched
      untreated patients over a median of 1.8 years. "Normalization" of right
      ventricular end-diastolic volume (RVEDV) and end systolic volume (ESV) after PVR
      occurred in the majority of patients during the study period, and no absolute
      ceiling beyond which the right ventricle did not normalize could be discerned. In
      a group of treated patients who were not matchable because of severe baseline
      characteristics, there was a significant improvement in resting cardiac output
      (CO) after PVR (from 2.9 to 3.3 L/min/m(2); p = 0.001). CONCLUSIONS: Our data
      indicate that patients with intermediate RV dilatation and severe PR are at low
      risk for significant progression in the short term, which can guide the interval
      for CMR imaging and advise the timing for future PVR.

PMID- 22959580
TI  - Limited blood transfusion does not impact survival in octogenarians undergoing
      cardiac operations.
AB  - BACKGROUND: We previously reported that transfusion of 1 to 2 units of red blood
      cells (RBCs) confers a 16% increased hazard of late death after cardiac surgical
      treatment. We explored whether a similar effect existed among octogenarians.
      METHODS: We enrolled 17,026 consecutive adult patients undergoing cardiac
      operations from 2001 to 2008 in northern New England. Patients receiving more
      than 2 units of RBCs or undergoing emergency operations were excluded. Early (to
      6 months) and late (to 3 years, among those surviving longer than 6 months)
      survival was confirmed using the Social Security Death Index. We estimated the
      relationship between RBCs and survival, and any interaction by age (<80 years
      versus >=80 years) or procedure. We calculated the adjusted hazard ratio (HR),
      and plotted adjusted survival curves. RESULTS: Patients receiving RBCs had more
      comorbidities irrespective of age. Patients 80 years of age or older underwent
      transfusion more often than patients younger than 80 years (51% versus 30%;
      p<0.001). There was no evidence of an interaction by age or procedure (p>0.05).
      Among patients younger than 80 years, RBCs significantly increased a patient's
      risk of early death [HR, 2.03; 95% confidence interval [CI], 1.47, 2.80] but not
      late death 1.21 (95%CI, 0.88, 1.67). RBCs did not increase the risk of early [HR,
      1.47; 95% CI, 0.84, 2.56] or late (HR, 0.92 95% CI, 0.50, 1.69) death in patients
      80 years or older. CONCLUSIONS: Octogenarians receive RBCs more often than do
      younger patients. Although transfusion of 1 to 2 units of RBCs increases the risk
      of early death in patients younger than 80 years, this effect was not present
      among octogenarians. There was no significant effect of RBCs in late death in
      either age group.

PMID- 22959581
TI  - Evidence for metabolic imbalance of vitamin A2 in wild fish chronically exposed
      to metals.
AB  - In a recent study on indigenous yellow perch chronically exposed to metals, we
      reported a negative correlation between liver metal concentration and liver
      transcription levels of genes encoding for enzymes involved in the metabolism of
      retinoids. We therefore speculated that metals, and especially the non-essential
      metal Cd, could alter the metabolism of retinoids in wild fish. Thus the present
      field study investigates the impact of in situ metal exposure on retinoid
      storage. A total of 55 yellow perch (Perca flavescens) were sampled in six lakes
      representing a metal contamination gradient (8<=N<=10 per lake). Our results show
      that yellow perch from Cd-contaminated lakes had significantly higher
      concentrations of liver dehydroretinol and dehydroretinyl esters than did fish
      from reference lakes. However, the increase in retinyl ester stores with
      increasing Cd concentrations was quantitatively much more important than the
      increase in free dehydroretinol. As a result, a significant decrease in the
      percentage of hepatic free dehydroretinol with increasing renal Cd concentrations
      was observed. These results suggest that the enzymes and the binding proteins
      involved in vitamin A homeostasis are inhibited by the presence of Cd.
      Alternatively, the increase in tissue vitamin A (antioxidant) levels could serve
      to better counteract the oxidative stress engendered by Cd exposure. Overall our
      findings illustrate that vitamin A(2) homeostasis can be altered as a consequence
      of chronic exposure to low Cd concentrations. Thus, in the context of
      environmental risk assessment, the percentage of liver free dehydroretinol can be
      considered as a biomarker of for in situ Cd exposure.

PMID- 22959582
TI  - In vitro MR imaging of renal stones with an ultra-short echo time magnetic
      resonance imaging sequence.
AB  - OBJECTIVES: To characterize the magnetic resonance (MR) relaxation times (ie, T1
      and T2 relaxation times) of a variety of kidney stone specimens using an ultra
      short echo time (UTE) sequence and to correlate these values to their size and
      composition based on chemical analysis. MATERIALS AND METHODS: This was an
      institutional review board-approved, Health Insurance Portability and
      Accountability Act-compliant study with waiver of informed consent. Between April
      2009 and September 2009, stones from 36 patients underwent 1.5T MR imaging with
      two UTE pulse sequences to measure: 1) T2 relaxation times (repetition time [TR]
      = 1 second and multiple echo times [TEs] ranging from 0.1 ms up to 2 ms); 2) T1
      relaxation times (TE = 0.1 ms and multiple TRs ranging from 500 ms to 2.5
      seconds). A tube containing a solution of water and hydroxyapatite crystals near
      the stones served as reference standard. Results were compared to previous data
      obtained from experiments measuring the T1 and T2 of pure calcium oxalate and
      hydroxyapatite crystals suspended in water. Stones were submitted for chemical
      analysis. The stone size and composition was correlated to the relaxation time,
      and signal intensity. RESULTS: The average stone size was 0.86 cm (range 0.1-3.3
      cm). Twenty-one stones were visible by MR. The average size of MR-visible stones
      was 1.1 cm (range 0.15-3.3 cm) compared to 0.46 cm (range 0.1-0.9) for nonvisible
      stones. The mean T1 and T2 of MR-visible stones were 950 ms (range 138-3000 ms)
      and 3.12 ms (range 0.27-12 ms), respectively. The T1 (mean 1143, range 740-1583)
      and T1 (mean 8.31, range 4.6-12) values of calcium phosphate were longer than
      that for other stone compositions T1 (mean 953, range 138-3000) and T2 (mean
      2.58, range 0.27-5.8; P < .05). CONCLUSIONS: The T1- and T2-relaxation times of
      kidney stones are variable and depend on their composition and the size of the
      stones. UTE MR allows for visualization of renal stones in vitro.

PMID- 22959583
TI  - In vivo endoluminal ultrasound biomicroscopic imaging in a mouse model of
      colorectal cancer.
AB  - RATIONALE AND OBJECTIVES: The gold-standard tool for colorectal cancer detection
      is colonoscopy, but it provides only mucosal surface visualization. Ultrasound
      biomicroscopy allows a clear delineation of the epithelium and adjacent colonic
      layers. The aim of this study was to design a system to generate endoluminal
      ultrasound biomicroscopic images of the mouse colon, in vivo, in an animal model
      of inflammation-associated colon cancer. MATERIALS AND METHODS: Thirteen mice
      (Mus musculus) were used. A 40-MHz miniprobe catheter was inserted into the
      accessory channel of a pediatric flexible bronchofiberscope. Control mice (n = 3)
      and mice treated with azoxymethane and dextran sulfate sodium (n = 10) were
      subjected to simultaneous endoluminal ultrasound biomicroscopy and white-light
      colonoscopy. The diagnosis obtained with endoluminal ultrasound biomicroscopy and
      colonoscopy was compared and confirmed by postmortem histopathology. RESULTS:
      Endoluminal ultrasound biomicroscopic images showed all layers of the normal
      colon and revealed lesions such as lymphoid hyperplasias and colon tumors.
      Additionally, endoluminal ultrasound biomicroscopy was able to detect two cases
      of mucosa layer thickening, confirmed by histology. Compared to histologic
      results, the sensitivities of endoluminal ultrasound biomicroscopy and
      colonoscopy were 0.95 and 0.83, respectively, and both methods achieved
      specificities of 1.0. CONCLUSIONS: Endoluminal ultrasound biomicroscopy can be
      used, in addition to colonoscopy, as a diagnostic method for colonic lesions.
      Moreover, experimental endoluminal ultrasound biomicroscopy in mouse models is
      feasible and might be used to further develop research on the differentiation
      between benign and malignant colonic diseases.

PMID- 22959584
TI  - Open injuries of the lower extremity: issues and unknown frontiers.

PMID- 22959585
TI  - [Acute traumatic spinal cord injuries: Epidemiology and prospects].
AB  - OBJECTIVE: Specify the epidemiological data on the acute spinal cord injuries and
      define a group of patients that could benefit from cellular transplantation
      therapy designed with the aim of repair and regeneration of damaged spinal cord
      tissues. MATERIAL AND METHODS: Five years monocentric (Gui-de-Chauliac Hospital,
      Montpellier, France) retrospective analysis of patients suffering from spinal
      cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor
      complete, underwent a clinical evaluation following American Spinal Injury
      Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2)
      scorings as well as radiological evaluation through spinal cord magnetic
      resonance imaging (MRI). RESULTS: One hundred and fifty-seven medical records
      were reviewed and we selected and re-examined 20 patients with complete thoracic
      spinal cord lesion. Clinical and radiological evaluations of these patients
      demonstrated, in 75 % of the cases, an absence of clinical progression after a
      mean of 49months. Radiological abnormalities were constantly present in the
      initial (at the admission to hospital) and control (re-evaluation) MRI and no
      reliable predictive criteria of prognosis had been found. DISCUSSION/CONCLUSION:
      We compare our results to the literature and discuss advantages and limits of
      cellular transplantation strategies for these patients.

PMID- 22959586
TI  - Influence of the HPA axis on the inflammatory response in cutaneous wounds with
      the use of 670-nm laser photobiomodulation.
AB  - This study evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis
      in cutaneous wounds subjected to laser biomodulation. A total of 48 rats were
      divided into two groups: Group I (GI) with 24 adrenalectomized animals and Group
      II (GII) with 24 non-adrenalectomized animals. Each group was divided into two
      subgroups: the irradiated subgroup which laser was applied to four points at the
      edges of the wound (670 nm laser, 9 mW) and control subgroup. Rats in each
      subgroup were sacrificed at 24 or 72 h. Adrenal glands were only removed from GI
      rats. Three days after adrenalectomy, a cutaneous wound was made. An
      immunohistochemical analysis was performed using anti-CD45 and anti-CD8
      antibodies. Flow cytometry was used to count T lymphocytes and their
      subpopulations in blood. Decreases in the number of CD45-positive inflammatory
      cells and in the total numbers of CD8- and CD45-positive cells were observed in
      histological sections of adrenalectomized animals subjected to laser
      biomodulation at 24h. Similar results were observed for distribution of total
      lymphocytes in blood (p<0.05). The action of 670 nm laser does not depend
      exclusively on HPA axis. It is believed that corticosteroid-promoting enzymes
      liberated in non-adrenal tissues may influence immune response under the
      influence of this type of phototherapy.

PMID- 22959587
TI  - [Hemophagocytic lymphohistiocytosis].
AB  - Hemophagocytic lymphohistiocytosis is a life-threatening condition associated
      with multiple organ dysfunctions. This entity is related to inappropriate
      stimulation and proliferation of cytotoxic lymphocytes and macrophages inducing
      phagocytosis of blood cells. Hemophagocytic lymphohistiocytosis should be
      considered rapidly in any unexplained febrile cytopenia. Biological markers are
      high ferritin and triglyceride levels, and low fibrinogen. Hemophagocytic
      lymphohistiocytosis diagnosis should not be ruled on or out solely on the
      presence or absence of hemophagocytosis features on smear or biopsy sampling. It
      is either "primary/genetic" (pediatric or familial disorders) and characterized
      by a lack of intrinsic cytotoxicity of NK cells or T CD8 lymphocyte, or
      "secondary/reactive" due to malignancy, infectious or autoimmune origin.
      Mortality is 50% (including all etiologies), and this severity requires rapid and
      "aggressive" investigations with multidisciplinary approach including intensive
      care unit team. The immediate aim of therapy is suppression of the severe hyper
      inflammation, which can lead to multiple organ failure. Emergency treatment is
      currently based on etoposide (VP16), pending to the identification and treatment
      of underlying cause.

PMID- 22959588
TI  - Long-term experiences after oesophagectomy/gastrectomy for cancer--a focus group
      study.
AB  - BACKGROUND: After surgery for oesophageal or gastric cancer, patients suffer from
      a variety of problems that affect their physical and mental health. Most previous
      studies on quality of life after this type of surgery are based on quantitative
      methods, and no studies to date have focused on the patient's subjective
      experiences of their quality of life from a long-term perspective. OBJECTIVE: To
      illuminate patients' experiences of their quality of life, and how they handle
      their new life situation, from a long-term perspective, after oesophagectomy or
      gastrectomy for cancer. METHOD: This study was carried out in accordance with a
      descriptive explorative design focusing on the patients' quality of life after
      surgery for oesophageal/gastric cancer. Data collection was carried out using
      semi-structured focus group interviews. A total of 17 participants divided into 4
      focus groups were included (2-5 years after elective surgery) in the study. Data
      was analysed with qualitative content analysis. RESULTS: The results show that
      the patients' lives are severely hampered by adverse symptoms long time after
      surgery. The patients experienced the recovery period as a struggle and the theme
      "When moving on becomes a struggle" was shown to capture the patients'
      experiences. The main problems that acts as barriers in the patients' new life
      situation are those connected with nutrition and diarrhea who was shown not only
      affecting the patients from a physical perspective but also on a social and
      emotional level. The feeling of losing control of life was shown as a prominent
      problem and resulted in anxiety and fear about the future. CONCLUSION: This study
      shows that the patients' quality of life is heavily influenced by the remaining
      symptoms for a long time after surgery. However the patients ability to handle
      their new life situation does not only depend on the remaining symptom but on
      their ability to take control of the new life situation and learn to live life
      with the symptoms instead of letting the symptoms limit their life. The complex
      new life situation that the patients meet after surgery motivates the needs of a
      supportive care programme, focusing on the patients' physical, mental and social
      needs.

PMID- 22959589
TI  - Direct-acting and host-targeting HCV inhibitors: current and future directions.
AB  - The inclusion of NS3 protease inhibitors to the interferon-containing standard of
      care improved sustained viral response rates in hepatitis C virus (HCV) infected
      patients. However, there is still an unmet medical need as this drug regimen is
      poorly tolerated and lacks efficacy, especially in difficult-to-treat patients.
      Intense drug discovery and development efforts have focused on direct-acting
      antivirals (DAA) that target NS3 protease, NS5B polymerase and the NS5A protein.
      DAA combinations are currently assessed in clinical trials. Alternative
      antivirals have emerged that target host machineries co-opted by HCV. Finally,
      continuous and better understanding of HCV biology allows speculating on the
      value of novel classes of DAA required in future personalized all-oral interferon
      free combination therapy and for supporting global disease eradication.

PMID- 22959590
TI  - Within-person vs. traditional study designs: how to evaluate study designs?

PMID- 22959591
TI  - The Cochrane Collaboration review prioritization projects show that a variety of
      approaches successfully identify high-priority topics.

PMID- 22959592
TI  - Preliminary state of development of prediction models for primary care physical
      therapy: a systematic review.
AB  - OBJECTIVE: To summarize the methodological quality and developmental stage of
      prediction models for musculoskeletal complaints that are relevant for physical
      therapists in primary care. STUDY DESIGN AND SETTING: A systematic literature
      search was carried out in the databases of Medline, Embase, and Cinahl. Studies
      on prediction models for musculoskeletal complaints that can be used by primary
      care physical therapists were included. Methodological quality of the studies was
      assessed and relevant study characteristics were extracted. RESULTS: The search
      retrieved 4,702 references of which 29 studies were included in this review. The
      study quality of the included studies showed substantial variation. The studied
      populations consisted mostly of back (n=10) and neck pain (n=6) patients, and
      patients with knee complaints (n=4). Most studies (n=22) used "perceived
      recovery" as primary outcome. Most prediction models (n=18) were at the
      derivation level of development. CONCLUSIONS: Many prediction models are
      available for a wide range of patient populations. The developmental stage of
      most models is preliminary and the study quality is often moderate. We do not
      recommend physiotherapist to use these models yet. All models reviewed here are
      in the developmental stage and need validation and impact evaluation before using
      them in daily practice.

PMID- 22959593
TI  - Perceived information gain from randomized trials correlates with publication in
      high-impact factor journals.
AB  - OBJECTIVE: To examine whether perceived information gain (IG) drives the
      publication of randomized trials in high-impact factor (IF) journals. STUDY
      DESIGN AND SETTING: We estimated IG as the Kullback-Leibler divergence,
      quantifying how much a new finding changes established knowledge. We used 67 meta
      analyses (964 randomized trials) that include one or more trials from any of the
      three highest IF general medical journals (NEJM, JAMA, and Lancet). We calculated
      IG for the presence of a non-null effect (IG(1)) and IG for the effect size
      magnitude (IG(2)). RESULTS: Across meta-analyses, the summary correlation
      coefficient of IF was 0.23 (95% confidence interval [CI]: 0.14, 0.31) for IG(1)
      and 0.35 (95% CI: 0.25, 0.46) for IG(2). IF also correlated with the P-value of
      the results (r=0.18), order of publication (r=-0.13), and number of events in the
      trial (r=0.36). Multivariate regression including IG, order of publication, P
      value, and the number of events showed that IG is an independent correlate of IF.
      IG(2) explained a substantially larger proportion of the variance in IF than
      IG(1). CONCLUSION: Publication in journals with high IF is driven by how
      extensively the results of a study change prior perceptions of the evidence,
      independently of the statistical significance and size of the study.

PMID- 22959594
TI  - Overviews of reviews often have limited rigor: a systematic review.
AB  - OBJECTIVE: To examine published overviews of systematic reviews in terms of
      descriptive and methodological characteristics. STUDY DESIGN AND SETTING:
      MEDLINE, Database of Abstracts of Reviews of Effects, the Cochrane Database of
      Systematic Reviews, and several Health Technology Assessment databases were
      searched for overviews of reviews up to February 2012. We extracted data from the
      methods and results sections of the included overviews. These data were analyzed
      descriptively as frequencies or medians and interquartile ranges. RESULTS: We
      included 126 overviews of reviews. According to our sample, publication rates for
      overviews have risen in the last decade. The quality of the included reviews was
      systematically appraised in 64% of the overviews. The most commonly used
      assessment tools were the Overview Quality Assessment Questionnaire (26%),
      Assessment of Multiple Systematic Reviews (11%), and Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (5%). Only three of 18 overviews
      restricted to Cochrane reviews in our sample performed a quality assessment.
      Strategies to deal with discordant reviews were reported in 5% of the overviews.
      Searches for additional primary studies were conducted in 5% of the overviews.
      CONCLUSION: Overviews of reviews often lack methodological rigor. Methodological
      standards and reporting guidelines for overviews are needed to improve the
      quality of this new publication type.

PMID- 22959595
TI  - Exosomes for drug delivery - a novel application for the mesenchymal stem cell.
AB  - Exosomes are the most extensively characterized class of secreted membrane
      vesicles that carry proteins and RNAs for intercellular communication. They are
      increasingly seen as possible alternatives to liposomes as drug delivery
      vehicles. Like liposomes, they could deliver their cargo across the plasma
      membrane and provide a barrier against premature transformation and elimination.
      In addition, these naturally-occurring secreted membrane vesicles are less toxic
      and better tolerated in the body as evidenced by their ubiquitous presence in
      biological fluids, and have an intrinsic homing ability. They are also amenable
      to in vivo and in vitro loading of therapeutic agents, and membrane modifications
      to enhance tissue-specific homing. Here we propose human mesenchymal stem cells
      as the ideal cell source of exosomes for drug delivery. Mesenchymal stem cell
      transplantation for various disease indications has been extensively tested and
      shown to be safe in numerous clinical trials. These cells are also prolific
      producers of immunologically inert exosomes. Immortalization of these cells does
      not compromise the quantity or quality of exosome production, thus enabling
      infinite and reproducible exosome production from a single cell clone. 

PMID- 22959596
TI  - [Life-sustaining treatment limitation criteria upon admission to the intensive
      care unit: results of a Spanish national multicenter survey].
AB  - OBJECTIVE: To determine the life-sustaining treatment limitation (LSTL)
      predisposition upon patient admission to the intensive care unit (ICU), the
      criteria upon which such predisposition is based, and whether these decisions are
      related to structural factors of the surveyed hospitals. DESIGN: A descriptive
      multicenter study was made in 2010, involving the conduction of a survey in 90
      hospitals, with a view to documenting the usual practice referred to LSTL upon
      admission in these centers. SETTING: Spanish ICUs. INTERVENTION: Opinion survey.
      MAIN VARIABLES OF INTEREST: Type of hospital, number of hospital beds, ICU and
      semicritical patient beds, usual bed availability in the ICU, use of restrictive
      admission criteria, use of LSTL criteria upon admission, and type of criterion
      used to decide LSTL. RESULTS: A total of 43 (48%) hospitals participated in the
      study, with LSTL being a common practice in these centers (93%). LSTL was
      fundamentally decided on the basis of the presence of prior severe chronic
      disease (95%), observation of previously declared patient will (95%), prior
      functional limitation (85%), and qualitative futility of care (82%). Frequent ICU
      bed availability (77% of the hospitals) and the use of restrictive criteria (79%
      of the hospitals) were also associated to patient admission with LSTL.
      CONCLUSIONS: Admission to ICU with LSTL is a generalized practice in Spanish
      Hospitals. LSTL is decided based on physiological futility from an objective
      medical point of view, but also in observance of ethical and moral implications
      based on the qualitative futility of medical care.

PMID- 22959597
TI  - Herpes simplex virus encephalitis requiring emergency surgery.

PMID- 22959598
TI  - Association of secondhand smoke exposure with mental health in men and women:
      cross-sectional and prospective analyses using the U.K. Health and Lifestyle
      Survey.
AB  - OBJECTIVES: We examine cross-sectional and prospective associations between
      objectively measured SHS exposure and mental health using data from the Health
      and Lifestyle Survey (HALS), a large, UK-wide, general population-based,
      prospective cohort study with measurements of carbon monoxide or salivary
      cotinine levels. METHODS: Mental health was assessed using the 30-item version of
      the General Health Questionnaire (GHQ). Multivariate logistic regression models
      adjusting for age, sex, height, body mass index, alcohol intake, social status,
      and longstanding illness were used to analyze the association between exposure to
      SHS (exhaled CO and salivary cotinine categories) and psychological distress
      (>=5GHQ). RESULTS: Fully adjusted cross-sectional analysis revealed a positive
      relationship between exhaled carbon monoxide and psychological distress among
      smokers (OR 1.36; 95% CI 1.04-1.78) but not among non-smoking adults. In a
      similar cross-sectional analysis between cotinine level and psychological
      distress, non-significant associations were found among smokers and non-smokers.
      Prospective analyses of the cotinine-psychological distress relationship among
      participants without psychological distress at baseline showed no significant
      increased risk of psychological distress among both smokers and non-smokers. In a
      prospective analysis of poor mental health outcome with respect to self-report
      smoking and SHS status, smokers had an increased risk of psychological distress
      while SHS and non-smokers did not. CONCLUSIONS: A non-significant association
      between objectively measured SHS exposure and poor mental health was found in
      this study. Our findings show discrepancies with recent studies suggesting the
      need for additional future research in this growing field of study.

PMID- 22959599
TI  - White matter integrity of the descending pain modulatory system is associated
      with interindividual differences in placebo analgesia.
AB  - The ability for endogenous pain control varies considerably among individuals.
      The mechanisms underlying this interindividual difference are incompletely
      understood. We used placebo analgesia as a classic model of endogenous pain
      modulation in combination with diffusion tensor magnetic resonance imaging to
      test the hypothesis of a structural predisposition for the individual capacity of
      endogenous pain control. Specifically we determined white matter integrity within
      and between regions of the descending pain modulatory system. Twenty-four healthy
      participants completed a placebo paradigm and underwent diffusion tensor magnetic
      resonance imaging. The individual placebo analgesic effect was correlated with
      white matter integrity indexed by fractional anisotropy. The individual placebo
      analgesic effect was positively correlated with FA in the right dorsolateral
      prefrontal cortex, left rostral anterior cingulate cortex, and the periaqueductal
      grey. Probabilistic tractography seeded in these regions showed that stronger
      placebo analgesic responses were associated with increased mean fractional
      anisotropy values within white matter tracts connecting the periaqueductal grey
      with pain control regions such as the rostral anterior cingulate cortex and the
      dorsolateral prefrontal cortex. Our findings provide the first evidence that the
      white matter integrity within and between regions of the descending pain
      modulatory network is critically linked with the individual ability for
      endogenous pain control.

PMID- 22959600
TI  - The burden of chronic pain: a cross-sectional survey focussing on diseases,
      immigration, and opioid use.
AB  - Chronic pain is currently considered a public health problem with high costs to
      the individual and society. To improve prevention and treatment of chronic pain,
      epidemiologic studies are mandatory for assessing chronic pain. The aims of this
      study were to estimate the prevalence of chronic pain in the adult Danish
      population and to analyze associated factors such as diseases, immigration, and
      opioid use. This cross-sectional survey combines individual-based information
      from the Danish Health Survey (2010) and official Danish health and
      socioeconomic, individual-based registers. The simple random sample consisted of
      25,000 individuals (>=16 years old) living in Denmark. In all, 60.7% completed a
      mailed or online questionnaire. Associations were examined with multiple logistic
      regression analysis. The study population consisted of 14,925 individuals in whom
      a high prevalence of chronic pain (26.8%, 95% confidence interval: 26.1 to 27.5)
      and a high prevalence of opioid consumption (4.5%) were observed. Other aspects
      of particular note: (1) a higher prevalence of chronic pain occurred among
      individuals with cardiovascular and chronic pulmonary diseases than among
      individuals with cancer; and (2) individuals with a non-Western background
      reported a higher pain prevalence, higher pain intensities, and more widespread
      pain than individuals with Danish background; however, opioids were more
      frequently used by native Danes. The prevalence of chronic pain as well as opioid
      use in Denmark are alarmingly high, and the relevance of opioid consumption is
      unknown.

PMID- 22959601
TI  - Vocal cord paralysis post patent ductus arteriosus ligation surgery: risks and co
      morbidities.
AB  - OBJECTIVES: 1. To determine the prevalence of left vocal cord paralysis (LVCP)
      post patent ductus arteriosus (PDA) ligation at a Tertiary Care Centre. 2. To
      identify risk factors associated with LVCP. 3. To identify co-morbidities
      associated with LVCP. 4. To determine the frequency of pre- and post-operative
      nasopharyngolaryngoscopic (NPL) examination in this patient population. METHODS:
      Retrospective chart review of all infants who underwent PDA ligation surgery at a
      tertiary care academic hospital between July 2003 and July 2010. Data on patient
      age, gender, weight, method of PDA ligation, and results of NPL scoping were
      collected, as well as patient co-morbidities post PDA ligation. RESULTS: One
      hundred and fifteen patients underwent PDA ligation surgery. Four patients were
      excluded due to bilateral vocal cord paralysis. Of the remaining 111 patients,
      nineteen patients (17.1%) were found to have LVCP. Low birth weight was
      identified as a significant risk factor for LVCP (p=0.002). Gastroesophageal
      reflux was identified as a significant co-morbidity associated with LVCP post PDA
      ligation (p=0.002). Only 0.9% of patients were scoped pre-operatively, and 27.9%
      were scoped postoperatively. CONCLUSIONS: LVCP is associated with multiple
      morbidities. The authors strongly recommend routine post-operative scoping of all
      patients post PDA ligation surgery, and preoperative scoping when possible. A
      prospective study is warranted, in order to confirm the prevalence of LVCP as
      well as risk factors and associated co-morbidities.

PMID- 22959602
TI  - Spatial and temporal variability of PCBs in Detroit River water assessed using a
      long term biomonitoring program.
AB  - An assessment of polychlorinated biphenyls (PCBs) in water of the Detroit River,
      North America, was performed using mussel biomonitoring data generated between
      1996 and 2010. The study included a temporal monitoring program at six locations
      and an enhanced spatial survey performed during 2002. Mussels were transplanted
      at biomonitoring stations and collected after 21-226 d. A toxicokinetic model was
      used to perform steady state and control corrections followed by an equilibrium
      partitioning model to estimate bioavailable water concentrations of PCBs.
      Bioavailable water concentrations of PCBs were similar in magnitude and trends to
      dissolved water concentrations reported in previous studies using direct sampling
      approaches. PCB concentrations exhibited complex temporal patterns at the six
      biomonitoring stations with multi-year declines in PCB trajectories between 1996
      and 2002 and less consistent trends occurring across stations in later years.
      Spatial patterns of PCBs during 2002 revealed significantly higher water
      contamination on the US side of the river (seasonal average mean +/- standard
      error (SE) sum PCB concentration of 0.63 +/- 0.11 ng L(-1)) compared to the
      Canadian side (mean +/- SE sum PCB concentration of 0.09 +/- 0.01 ng L(-1)).
      Spatial/temporal variability of bioavailable PCB concentrations was greatest
      between countries, followed by moderate variation across years and by river reach
      (upstream, midstream and downstream sections within a country) and lowest when
      comparing intra-seasonal variation.

PMID- 22959603
TI  - Results of a randomized controlled pilot study of a self-management intervention
      for cancer pain.
AB  - PURPOSE OF THE RESEARCH: This paper reports findings from a randomized controlled
      pilot study evaluating the PRO-SELF Plus Pain Control Program, a U.S.-developed
      cancer pain self-management intervention, regarding feasibility and effect sizes
      in a German patient sample. METHODS AND SAMPLE: Thirty-nine German oncology
      outpatients were randomized to intervention (n = 19) and control (n = 20) groups.
      The intervention group received the PRO-SELF Plus Pain Control Program in 6
      visits and 4 phone calls a 10-week period. The control group received standard
      education and care. The intervention employed three key strategies: information
      provision, skills building, and nurse coaching. Primary outcomes were changes in
      average and worst pain intensity. Secondary outcomes included changes in pain
      related knowledge, opioid intake, and self-efficacy. Data were collected at
      enrollment, then at 6, 10, 14, and 22 weeks. KEY RESULTS: The group-by-time
      effect showed a statistically significant increase in knowledge (week 10: p =
      0.04; week 22: p < 0.01). Despite slight reductions in average and worst pain, no
      statistically significant changes were found for pain, opioid intake, or self
      efficacy. CONCLUSIONS: This study is the first to evaluate and demonstrate the
      feasibility of a U.S.-developed cancer pain self-management intervention in a
      German patient population. Pain self-management related knowledge improved
      significantly and effect sizes for pain reduction were determined. Findings from
      this pilot RCT provide the basis for planning a larger RCT. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00920504.

PMID- 22959604
TI  - Equine G3P[3] rotavirus strain E3198 related to simian RRV and feline/canine-like
      rotaviruses based on complete genome analyses.
AB  - Equine group A rotavirus (RVA) strains are the most important cause of
      gastroenteritis in equine neonates and foals worldwide, and G3P[12] and G14P[12]
      are epidemiologically the most important genotypes. The genotype constellation of
      an unusual Argentinean G3P[3] RVA strain (RVA/Horse-wt/E3198/2008/G3P[3])
      detected in fecal samples of a diarrheic foal in 2008 was shown to be G3-P[3]-I3
      R3-C3-M3-A9-N3-T3-E3-H6. Each of these genotypes has been found typically in
      feline and canine RVA strains, and the genotype constellation is reminiscent to
      those of Cat97-like RVA strains. However, the phylogenetic analyses revealed only
      a distant relationship between E3198 and known feline, canine and feline/canine
      like human RVA strains. Surprisingly, a rather close relationship was found
      between E3198 and simian RVA strains RVA/Simian-tc/USA/RRV/1975/G3P[3] for at
      least 5 gene segments. RRV is believed to be a reassortant between a bovine-like
      RVA strain and a RVA strains distantly related to feline/canine RVA strains.
      These analyses indicate that E3198 is unlikely to be of equine origin, and most
      likely represents a RVA interspecies transmitted virus, possibly in combination
      with one or more reassortments, from a feline, canine or related host species to
      a horse. Further studies are in progress to evaluate if this strain was a single
      interspecies transmission event, or if this strain started to circulate in the
      equine population.

PMID- 22959605
TI  - Detecting frailty in primary care: a major challenge for primary care physicians.

PMID- 22959606
TI  - Comparison of open and arthroscopic subacromial decompression.
AB  - We retrospectively reviewed 68 patients (70 shoulders) who underwent either open
      or arthroscopic acromioplasty performed by a single surgeon (JPI) for chronic
      impingement syndrome in the presence of an intact rotator cuff. Group 1 consisted
      of 24 shoulders that had open acromioplasty and group 2 consisted of 46 shoulders
      that had arthroscopic acromioplasty. The minimum follow-up was 12 months for both
      groups. There was no statistical difference in mean postoperative shoulder scores
      between the operative groups. However, there were more excellent results in the
      open group as compared with the arthroscopic group (54.2% vs 41.9%,
      respectively). In addition, there was a higher percentage of poor results in
      group 2 as compared with group 1 (27.9% vs 16.6%, respectively). Arthroscopic
      acromioplasty was associated with shorter hospital stays and faster achievement
      of maximal pain relief as compared with open acromioplasty. Examination of
      postoperative radiographs often revealed subacromial calcifications. These
      calcifications were more frequent after arthroscopic acromioplasty and were
      associated with a worse result.

PMID- 22959607
TI  - The shoulder impingement syndrome: The results of surgical decompression.
AB  - Forty patients (41 operated shoulders) with subacromial impingement resistant to
      conservative therapy underwent acomioplasty and were evaluated 6 to 142 months
      after surgery. Patients requiring rotator cuff repair were excluded from the
      study. With the UCLA scoring system, results were excellent or good in 28 (68%),
      fair in five (12%), and poor in eight (20%). Thirty-three (80%) were satisfied
      with their result. There was a trend toward poorer results in women and in the
      elderly (aged 60 to 69 years). A striking finding was the statistically
      significant relationship between result rating and duration of symptoms. Ninety
      three percent had an excellent or good result, if they had been symptomatic for
      greater than 3 years, whereas only 56% reached those ratings with symptom
      duration less than 3 years. The only complication was a superficial infection.
      Three patients required manipulation after the procedure. Two required subsequent
      surgery because of continuing pain. This procedure seems safe and reasonably
      effective. Careful patient selection must be stressed. Results will be better
      with a longer preoperative duration of symptoms.

PMID- 22959608
TI  - Late complications with the Pritchard Mark II elbow prosthesis.
AB  - Twenty-three consecutive patients with rheumatoid arthritis who had 26 Pritchord
      Mark II elbow prostheses were followed prospectively with a mean follow-up of 75
      months (range 52 to 101 months). Two patients with three elbow prostheses have
      died, leaving 21 patients with 23 elbow prostheses for review. At the latest
      follow-up all the nonrevised elbows had achieved good or excellent results
      concerning pain relief and elbow motion. According to the data analyzed by a
      survivorship function-a Kaplan-Meier curve-the early results were promising with
      92% of the prostheses surviving the first 5 years; however, only 43% of the
      prostheses have survived 8 years. Seven prostheses have been revised; the reasons
      for revision include one infection, one humeral fracture, one loosening of the
      humeral component, and four disconnections of the hinge. The number with
      disconnection of the hinge is increasing. Of 16 prostheses still not revised, the
      x-ray film reveals migration of the pin axle in six. Radiographic signs of
      component loosening or migration of the axle are not reflected in pain, function,
      or total score of the elbow.

PMID- 22959609
TI  - Classification of proximal humerus fractures: The contribution of the scapular
      lateral and axillary radiographs.
AB  - Trauma series radiographs of 50 proximal humerus fractures were used to assess
      the relative contribution of the scapular lateral and axillary radiographs to
      fracture classification with the Neer system. The radiographs were reviewed by an
      orthopaedic shoulder specialist, on orthopaedic traumatologist, a skeletal
      radiologist, and orthopaedic residents in their fifth and second years,
      respectively, of postgraduate training. In the first viewing radiographs were
      reviewed and classified in the following sequence: (1) after scapular
      anteroposterior view alone; (2) after review of scapular anteroposterior and
      lateral views; and (3) after review of scapular anteroposterior, lateral, and
      axillary views. A second viewing of the same 50 cases was performed 6 months
      later in a changed sequence: (1) after scapular anteroposterior view alone; (2)
      after review of scapular anteroposterior and axillary views; and (3) after review
      of scapular anteroposterior, axillary, and scapular lateral views. For the five
      observers, review of the scapular anteroposterior and axillary views achieved the
      final classification in 99% of cases. However, after review of the scapular
      anteroposterior and lateral views, the final classification was achieved in only
      79% of cases (p < 0.05). These results indicate that when combined with the
      scapular anteroposterior radiograph, the axillary view contributes significantly
      more to fracture classification with the Neer system than the scapular lateral
      radiograph.

PMID- 22959610
TI  - Long thoracic nerve paralysis associated with thoracic outlet syndrome.
AB  - Two cases of long thoracic nerve palsy associated with thoracic outlet syndrome
      are reported. Both patients had abnormal posture, with low-set shoulders and
      winged scapulae. Clinically there was weakness of the serratus anterior muscle
      with partial denervotion on electromyography. The diagnosis of thoracic outlet
      syndrome was based on positive vascular tests and brachial plexus nerve
      compression symptoms induced by the vascular testing positions. An orthosis that
      held the shoulder in an elevated position was used in both cases. Complete
      recovery of shoulder function and relief of the symptoms was achieved in both
      cases at 8 and 13 months, respectively, after application of the orthosis.

PMID- 22959611
TI  - Ganglion cysts about the shoulder girdle in the absence of suprascapular nerve
      involvement.
AB  - Ganglion cysts about the shoulder girdle are being identified with increasing
      frequency by the magnetic resonance image scanner. These masses rarely become
      evident clinically unless they cause compression of the suprascapular nerve. In
      this series a ganglion not causing compression of the suprascapular nerve was
      identified in each of five patients. Three of these patients had shoulder pain,
      tenderness over the supraspinotus muscle, and an increase in pain with abduction
      in the plane of the scapula. Plain radiographs showed erosion of the scapular
      neck. In the remaining two patients the pain pattern was consistent with an
      impingement syndrome in one and a rotator cuff tear in the other. Successful
      operative resection was undertaken on three patients. In two of these patients
      the magnetic resonance image scan helped determine the need for simultaneous
      exposure of the suprospinous and infraspinous fossae by means of scapular spine
      osteotomy. In the two patients not believed to be symptomatic from their ganglia,
      treatment for the primary shoulder diagnosis resulted in complete relief of
      symptoms. In the absence of suprascapular nerve involvement, the presence of a
      ganglion cyst in the shoulder girdle is not an absolute indication for operative
      resection. In the presence of another common shoulder diagnosis, treatment for
      that diagnosis should be pursued.

PMID- 22959612
TI  - Fractures of the glenoid neck.
AB  - Glenoid neck fractures are uncommon and have received little attention in the
      literature. However, these injuries involve a major articulation and can cause
      considerable morbidity if significantly displaced. Consequently, a review of
      current diagnostic and therapeutic principles with respect to these potentially
      challenging fractures is justified. The vast majority of glenoid neck fractures
      are undisplaced or insignificantly displaced (Type I fractures) and are managed
      without surgery. Type II fractures, however, are significantly displaced, making
      surgical management a consideration. Significant displacement is defined as
      translational displacement greater than or equal to 1 cm or angulatory
      displacement greater than or equal to 40 degrees  (in either the coronol or
      transverse plane). The primary surgical approach is posterior; however, a
      superior extension is often necessary. Fixation devices include K-wires, 3.5 mm
      reconstruction plates, and 3.5 mm cannulated lag screws. Follow-up care and
      rehabilitation are absolutely critical to optimizing the final functional result.

PMID- 22959613
TI  - Evolution of the beta-barrel assembly machinery.
AB  - Proteins from the Omp85 family have roles in membrane biogenesis, and the
      archetypal protein of this family is the bacterial outer membrane protein BamA.
      Through evolution, BamA has acquired membrane protein partner subunits, but
      distinct partner subunits are evident in the various bacterial lineages. As a
      result, experimental work on several species of bacteria has revealed varietal
      forms of the beta-barrel assembly machinery (BAM complex). This scenario extends
      even into mitochondria and plastids, organelles of eukaryotic cells that evolved
      from intracellular bacterial ancestors. In addition to the BAM complex, other
      molecular machines, namely the two-partner secretion system (TPS) and the
      translocation and assembly module (the TAM), probably evolved from gene
      duplication events involving BamA. We discuss what is known about the diverse
      composition of the BAM complex in various bacterial lineages, and how this
      diversity impacts on our understanding of the mechanism underlying the assembly
      of bacterial outer membranes.

PMID- 22959615
TI  - New-found fundamentals of bacterial persistence.
AB  - Persister cells display tolerance to high doses of bactericidal antibiotics and
      typically comprise a small fraction of a bacterial population. Recently, evidence
      was provided for a causal link between therapy failure and the presence of
      persister cells in chronic infections, underscoring the need for research on
      bacterial persistence. A series of recent breakthroughs have shed light on the
      multiplicity of persister genes, the contribution of gene expression noise to
      persister formation, the importance of active responses to antibiotic tolerance
      and heterogeneity among persister cells. Moreover, the development of in vivo
      model systems has highlighted the clinical relevance of persistence. This review
      discusses these recent advances and how this knowledge fundamentally changes the
      way in which we will perceive the problem of antibiotic tolerance in years to
      come.

PMID- 22959614
TI  - Pneumococcal carbohydrate transport: food for thought.
AB  - Streptococcus pneumoniae relies exclusively on carbohydrates as a carbon source
      and devotes 30% of all transport mechanisms to carbohydrate import. Pneumococci
      utilize at least 32 carbohydrates in vitro. However, some proposed substrates are
      not human-derived, so it is unclear where they are encountered in the host niche,
      and other substrates remain unidentified. The majority of transporter loci are
      conserved, arguing against redundancy and instead for distinct roles during
      pathogenesis. Despite this, expression and regulation of carbohydrate
      transporters in vivo remain ill defined. Recent work has also demonstrated that
      multiple ABC transporters share an ATPase; whether this evolved for genome
      minimization or for transporter regulation remains unknown. Continued efforts to
      understand carbohydrate import may reveal novel vaccine and therapeutic targets
      and increase our understanding of pneumococcal pathogenesis.

PMID- 22959616
TI  - Classifying performance impairment in response to sleep loss using pattern
      recognition algorithms on single session testing.
AB  - There is currently no "gold standard" marker of cognitive performance impairment
      resulting from sleep loss. We utilized pattern recognition algorithms to
      determine which features of data collected under controlled laboratory conditions
      could most reliably identify cognitive performance impairment in response to
      sleep loss using data from only one testing session, such as would occur in the
      "real world" or field conditions. A training set for testing the pattern
      recognition algorithms was developed using objective Psychomotor Vigilance Task
      (PVT) and subjective Karolinska Sleepiness Scale (KSS) data collected from
      laboratory studies during which subjects were sleep deprived for 26-52h. The
      algorithm was then tested in data from both laboratory and field experiments. The
      pattern recognition algorithm was able to identify performance impairment with a
      single testing session in individuals studied under laboratory conditions using
      PVT, KSS, length of time awake and time of day information with sensitivity and
      specificity as high as 82%. When this algorithm was tested on data collected
      under real-world conditions from individuals whose data were not in the training
      set, accuracy of predictions for individuals categorized with low performance
      impairment were as high as 98%. Predictions for medium and severe performance
      impairment were less accurate. We conclude that pattern recognition algorithms
      may be a promising method for identifying performance impairment in individuals
      using only current information about the individual's behavior. Single testing
      features (e.g., number of PVT lapses) with high correlation with performance
      impairment in the laboratory setting may not be the best indicators of
      performance impairment under real-world conditions. Pattern recognition
      algorithms should be further tested for their ability to be used in conjunction
      with other assessments of sleepiness in real-world conditions to quantify
      performance impairment in response to sleep loss.

PMID- 22959617
TI  - Ficolins in complement activation.
AB  - Ficolins are a group of multimeric lectins made up of single subunits each of
      which is composed of a collagen-like domain and a fibrinogen-like domain. Most of
      the ficolins identified to date bind to acetylated compounds such as N
      acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc). Ficolins in serum
      are complexed with MBL-associated serine proteases (MASPs) and their truncated
      proteins. These lectins play an important role in innate immunity. Binding of the
      ficolin-MASP complex to carbohydrates present on the surface of microbes
      initiates complement activation via the lectin pathway.

PMID- 22959618
TI  - Permeability studies of artificial and natural cancellous bone structures.
AB  - In the development of artificial cancellous bones, two major factors need to be
      considered: the integrity of the overall structure and its permeability. Whilst
      there have been many studies analysing the mechanical properties of artificial
      and natural cancellous bones, permeability studies, especially those using
      numerical simulation, are scarce. In this study, idealised cancellous bones were
      simulated from the morphological indices of natural cancellous bone. Three
      different orientations were also simulated to compare the anisotropic nature of
      the structure. Computational fluid dynamics methods were used to analyse fluid
      flow through the cancellous structures. A constant mass flow rate was used to
      determine the intrinsic permeability of the virtual specimens. The results showed
      similar permeability of the prismatic plate-and-rod model to the natural
      cancellous bone. The tetrakaidecahedral rod model had the highest permeability
      under simulated blood flow conditions, but the plate counterpart had the lowest.
      Analyses on the anisotropy of the virtual specimens showed the highest
      permeability for the horizontal orientation. Linear relationships were found
      between permeability and the two physical properties, porosity and bone surface
      area.

PMID- 22959619
TI  - X-rays sensing properties of MEH-PPV, Alq3 and additive components: a new organic
      dosimeter as a candidate for minimizing the risk of accidents of patients
      undergoing radiation oncology.
AB  - In this paper, we report our experimental design in searching a smart and easy-to
      read dosimeter used to detect 6 MV X-rays for improving patient safety in
      radiation oncology. The device was based on an organic emissive solutions of
      poly(2-methoxy-5(2'-ethylhexyloxy)-p-phenylenevinylene) (MEH-PPV), aluminum-tris
      (8-hydroxyquinoline) (Alq3) and additive components which were characterized by
      UV-Vis absorption, photoluminescence and CIE color coordinate diagram. The
      optical properties of MEH-PPV/Alq3 solutions have been examined as function of
      radiation dose over the range of 0-100 Gy. It has shown that MEH-PPV/Alq3
      solutions are specifically sensitive to X-rays, since the effect of radiation on
      this organic system is strongly correlated with the efficient spectral overlap
      between Alq3 emission and the absorption of degraded MEH-PPV, which alters the
      color and photoemission of MEH-PPV/Alq3 mixtures from red to yellow, and then to
      green. The rate of this change is more sensitive when MEH-PPV/Alq3 is irradiated
      in the presence of benzoyl peroxide than when in the presence of hindered
      phenolic stabilizers, respectively, an accelerator and an inhibitor to activate
      or inhibit free radical formation. This gives rise to optimize the response curve
      of the dosimeter. It is clear from the experimental results that organic emissive
      semiconductors have potential to be used as dedicated and low-cost dosimeters to
      provide an independent check of beam output of a linear accelerator and therefore
      to give patients the opportunity to have information on the dose prescription or
      equipment-related problems a few minutes before being exposed to radiation.

PMID- 22959620
TI  - Effect of synbiotic in constipated adult women - a randomized, double-blind,
      placebo-controlled study of clinical response.
AB  - BACKGROUND & AIMS: Synbiotic intake may selectively change microbiota
      composition, restore microbial balance in the gut and improve gastrointestinal
      functions. We have assessed the clinical response of chronically constipated
      women to a commercially available synbiotic, combining fructooligosaccharides
      with Lactobacillus and Bifidobacterium strains (LACTOFOS(r)). METHODS: Following
      1 week of non-interventional clinical observation, 100 constipated adult women,
      diagnosed by ROME III criteria, were randomized to receive two daily doses (6 g)
      of synbiotic or maltodextrin (placebo group), for 30 days. Treatment response was
      evaluated by patient's daily record of evacuation (stool frequency, consistency
      and shape, according to Bristol scale), abdominal symptoms (abdominal pain,
      bloating and flatulence) and constipation intensity (Constipation Scoring System
      AGACHAN). RESULTS: Patients treated with synbiotic had increased frequency of
      evacuation, as well as stool consistency and shape nearer normal parameters than
      the placebo group, with significant benefits starting during the second and third
      weeks, respectively (interaction group/time, P<0.0001). There were no significant
      differences in abdominal symptoms, but AGACHAN score was better in the synbiotic
      than in the placebo group. CONCLUSIONS: Dietary supplementation with a synbiotic
      composed of fructooligosaccharides with Lactobacillus and Bifidobacterium
      improved evacuation parameters and constipation intensity of chronically
      constipated women, without influencing abdominal symptoms.

PMID- 22959621
TI  - Acute glycaemic load breakfast manipulations do not attenuate cognitive
      impairments in adults with type 2 diabetes.
AB  - BACKGROUND & AIMS: Research on young healthy samples suggests that low glycaemic
      load foods can confer benefits for cognitive performance. The aim was to examine
      the effects of type 2 diabetes on cognitive function, and to investigate whether
      consumption of low glycaemic load breakfasts affects cognitive function in adults
      with type 2 diabetes. METHOD: Memory, psychomotor skill and executive function
      were examined at two morning test sessions in 24 adults with type 2 diabetes and
      10 adults with normal glucose tolerance (NGT) aged 45-77 years without dementia
      after water, low, and high glycaemic load breakfasts were consumed in accordance
      with a crossover, counterbalanced design. The type 2 diabetes and NGT groups were
      matched for education, depression, and IQ. RESULTS: Type 2 diabetes was
      associated with impairments in verbal memory, spatial memory, psychomotor skill,
      and executive function compared to adults with NGT. Consumption of the three
      breakfast conditions did not impact on cognitive performance in the type 2
      diabetes or NGT participants. CONCLUSIONS: Abnormalities in glucose tolerance
      such as type 2 diabetes can have demonstrable negative effects on a range of
      cognitive functions. However, there was no evidence that low GL breakfasts
      administered acutely could confer benefits for cognitive function
      (ClincalTrials.gov identifier, NCT01047813).

PMID- 22959622
TI  - An RTX transporter tethers its unfolded substrate during secretion via a unique N
      terminal domain.
AB  - Type 1 secretion systems (T1SS) catalyze the one step protein transport across
      the membranes of Gram-negative bacteria and are composed of an outer membrane
      protein, a membrane fusion protein and an ABC transporter. The ABC transporter
      consists of the canonical nucleotide binding and transmembrane domains. For the
      toxin hemolysin A (HlyA), the ABC transporter HlyB carries an additional, N
      terminal domain sharing about 40% homology to C39 peptidases, but this "C39-like
      domain" (CLD) is suggested to feature another, yet unknown function. Our
      functional and structural analysis demonstrates that the CLD is essential for
      secretion and that it specifically interacts with the unfolded state of HlyA. We
      determined the nuclear magnetic resonance structure of the CLD as well as the
      substrate-binding region within the CLD. This mode of action, represents a
      mechanism within T1SS and answers the question, how a large and unfolded
      substrate is protected inside the cells during secretion.

PMID- 22959623
TI  - Structures of dNTP intermediate states during DNA polymerase active site
      assembly.
AB  - DNA polymerase and substrate conformational changes are essential for high
      fidelity DNA synthesis. Structures of DNA polymerase (pol) beta in complex with
      DNA show the enzyme in an "open" conformation. Subsequent to binding the
      nucleotide, the polymerase "closes" around the nascent base pair with two metals
      positioned for chemistry. However, structures of substrate/active site
      intermediates prior to closure are lacking. By destabilizing the closed complex,
      we determined unique ternary complex structures of pol beta with correct and
      incorrect incoming nucleotides bound to the open conformation. These structures
      reveal that Watson-Crick hydrogen bonding is assessed upon initial complex
      formation. Importantly, nucleotide-bound states representing intermediate metal
      coordination states occur with active site assembly. The correct, but not
      incorrect, nucleotide maintains Watson-Crick hydrogen bonds during
      interconversion of these states. These structures indicate that the triphosphate
      of the incoming nucleotide undergoes rearrangement prior to closure, providing an
      opportunity to deter misinsertion and increase fidelity.

PMID- 22959624
TI  - The CDK9 tail determines the reaction pathway of positive transcription
      elongation factor b.
AB  - CDK9, the kinase of positive transcription elongation factor b (P-TEFb),
      stimulates transcription elongation by phosphorylating RNA polymerase II and
      transcription elongation factors. Using kinetic analysis of a human P-TEFb
      complex consisting of CDK9 and cyclin T, we show that the CDK9 C-terminal tail
      sequence is important for the catalytic mechanism and imposes an ordered binding
      of substrates and release of products. Crystallographic analysis of a CDK9/cyclin
      T complex in which the C-terminal tail partially blocks the ATP binding site
      reveals a possible reaction intermediate. Biochemical characterization of CDK9
      mutants supports a model in which the CDK9 tail cycles through different
      conformational states. We propose that this mechanism is critical for the pattern
      of CTD Ser2 phosphorylation on actively transcribed genes.

PMID- 22959626
TI  - CHIT1 genetic defects in the Portuguese population.
AB  - Chitotriosidase is an enzyme secreted by activated macrophages and a useful
      biomarker in several lysosomal and nonlysosomal diseases. However,
      chitotriosidase gene (CHIT1) mutations may lead to inaccuracy in the significance
      of this biomarker. Reports on the molecular spectrum of genetic variation in
      chitotriosidase are rare, and this is one of the few that focus on a specific
      population group. In this work we assessed the variation of CHIT1 mutations in
      ten normal controls and detected six missense alterations. G102S, a polymorphism
      with known altered catalytic properties, was the most frequent being detected in
      4/10 individuals. Using allelic discrimination we tested 503 individuals,
      randomly sampled from the Portuguese population. Variant G102S was detected in
      49.5% of the individuals and presented an allele frequency of 0.29. The results
      of this study showed that variability in CHIT1 gene is considerable and that
      G102S polymorphism presents a high frequency in the Portuguese.

PMID- 22959625
TI  - Comparative dynamics of NMDA- and AMPA-glutamate receptor N-terminal domains.
AB  - Ionotropic glutamate receptors (iGluRs) harbor two extracellular domains: the
      membrane-proximal ligand-binding domain (LBD) and the distal N-terminal domain
      (NTD). These are involved in signal sensing: the LBD binds L-glutamate, which
      activates the receptor channel. Ligand binding to the NTD modulates channel
      function in the NMDA receptor subfamily of iGluRs, which has not been observed
      for the AMPAR subfamily to date. Structural data suggest that AMPAR NTDs are
      packed into tight dimers and have lost their signaling potential. Here, we assess
      NTD dynamics from both subfamilies, using a variety of computational tools. We
      describe the conformational motions that underly NMDAR NTD allosteric signaling.
      Unexpectedly, AMPAR NTDs are capable of undergoing similar dynamics; although
      dimerization imposes restrictions, the two subfamilies sample similar,
      interconvertible conformational subspaces. Finally, we solve the crystal
      structure of AMPAR GluA4 NTD, and combined with molecular dynamics simulations,
      we characterize regions pivotal for an as-yet-unexplored dynamic spectrum of
      AMPAR NTDs.

PMID- 22959627
TI  - In vitro evaluation of the antimicrobial activity of a range of probiotics
      against pathogens: evidence for the effects of organic acids.
AB  - The aim of this study was to investigate the antimicrobial properties of fifteen
      selected strains belonging to the Lactobacillus, Bifidobacterium, Lactococcus,
      Streptococcus and Bacillus genera against Gram-positive and Gram-negative
      pathogenic bacteria. In vitro antibacterial activity was initially investigated
      by an agar spot method. Results from the agar spot test showed that most of the
      selected strains were able to produce active compounds on solid media with
      antagonistic properties against Salmonella Typhimurium, Escherichia coli,
      Enterococcus faecalis, Staphylococcus aureus and Clostridium difficile. These
      results were also confirmed when cell-free culture supernatants (CFCS) from the
      putative probiotics were used in an agar well diffusion assay. Neutralization of
      the culture supernatants with alkali reduced the antagonistic effects. These
      experiments are able to confirm the capacity of potential probiotics to inhibit
      selected pathogens. One of the main inhibitory mechanisms may result from the
      production of organic acids from glucose fermentation and consequent lowering of
      culture pH. This observation was confirmed when the profile of organic acids was
      analysed demonstrating that lactic and acetic acid were the principal end
      products of probiotic metabolism. Furthermore, the assessment of the haemolytic
      activity and the susceptibility of the strains to the most commonly used
      antimicrobials, considered as basic safety aspects, were also studied. The
      observed antimicrobial activity was mainly genus-specific, additionally
      significant differences could be observed among species.

PMID- 22959628
TI  - Bagging, bumping, multiview, and active learning for record linkage with
      empirical results on patient identity data.
AB  - Record linkage or deduplication deals with the detection and deletion of
      duplicates in and across files. For this task, this paper introduces and
      evaluates two new machine-learning methods (bumping and multiview) together with
      bagging, a tree-based ensemble-approach. Whereas bumping represents a tree-based
      approach as well, multiview is based on the combination of different methods and
      the semi-supervised learning principle. After providing a theoretical background
      of the methods, initial empirical results on patient identity data are given. In
      the empirical evaluation, we calibrate the methods on three different kinds of
      training data. The results show that the smallest training data set, which is
      obtained by a simple active learning strategy, leads to the best results.
      Multiview can outperform the other methods only when all are calibrated on a
      randomly sampled training set; in all other cases, it performs worse. The results
      of bumping do not differ significantly from the overall best performing method
      bagging. We cautiously conclude that tree-based record linkage methods are likely
      to produce similar results because of the low-dimensionality (p?n) and
      straightforwardness of the underlying problem. Multiview is possibly rather
      suitable for problems that are more sophisticated.

PMID- 22959629
TI  - METRADISC-XL: a program for meta-analysis of multidimensional ranked discovery
      oriented datasets including microarrays.
AB  - A comprehensive software for performing meta-analysis of ranked discovery
      oriented datasets, such as those derived from microarrays or other high
      throughput technologies, and for testing between-study heterogeneity for
      biological variables (gene expression, microRNA, proteomic, or other high
      dimensional data) is presented. The software can identify biological probes that
      have either very high average ranks (e.g. consistently over-expressed genes) or
      very low average ranks (e.g. consistently under-expressed genes). The program
      tests each probe's average rank and the between-study heterogeneity of the study
      specific ranks. Furthermore, it performs heterogeneity analyses restricted to
      probes with similar average ranks. The program allows both unweighted and
      weighted analysis. Statistical inferences are based on Monte Carlo permutation
      tests.

PMID- 22959630
TI  - Epidemiology of catheter-related infections in adult patients receiving home
      parenteral nutrition: a systematic review.
AB  - BACKGROUND AND AIMS: Catheter-related infection (CRI) is the most common and
      serious complication for adult patients receiving home parenteral nutrition
      (HPN). Our aim is to provide epidemiological data on infection incidence,
      infecting pathogens and contributing risk factors. METHODS: Four electronic
      databases (Embase, Medline, IPA, CINAHL) were screened for eligible studies
      published between 1970 and March 2012. Methodological quality was evaluated and
      terminology/definitions were re-categorized. RESULTS: Thirty-nine studies were
      included. Extensive variability was observed in terminology/definitions as well
      as in expression of CRI rate. After correct interpretation of definitions,
      overall catheter-related bloodstream infection rate (CRBSI) ranged between 0.38
      and 4.58 episodes/1000 catheter days (median 1.31). Gram-positive bacteria of
      human skin flora caused more than half of infections. An analysis of the reported
      risk factors showed that the origin of a CRBSI is often multifactorial. The risk
      factors were related to the patient, the venous access device, the education, HPN
      therapy and follow-up. CONCLUSIONS: This review on CRI in adult HPN patients
      revealed that included studies are of low quality and used poorly described risk
      factors and different definitions. The human skin flora caused most of
      infections; therefore, hand hygiene and training remain essential.

PMID- 22959631
TI  - Intimate partner violence, abortion, and unintended pregnancy: results from the
      WHO Multi-country Study on Women's Health and Domestic Violence.
AB  - OBJECTIVE: To explore how intimate partner violence (IPV) is associated with
      unintended pregnancy and abortion in primarily low- and middle-income countries.
      METHODS: Population data are presented from 17 518 ever-partnered women
      participating in the WHO Multi-country Study on Women's Health and Domestic
      Violence in 15 sites in 10 countries. Using multiple logistic regression
      analyses, associations between physical and/or sexual partner violence and
      abortion and unintended pregnancy were explored. RESULTS: Women with a history of
      IPV had significantly higher odds of unintended pregnancy in 8 of 14 sites and of
      abortion in 12 of 15 sites. Pooled estimates showed increased odds of unintended
      pregnancy (adjusted OR 1.69; 95% CI, 1.53-1.86) and abortion (adjusted OR 2.68;
      95% CI, 2.34-3.06), after adjusting for confounding factors. Reducing IPV by 50%
      could potentially reduce unintended pregnancy by 2%-18% and abortion by 4.5%-40%,
      according to population-attributable risk estimates. CONCLUSION: IPV is a
      consistent and strong risk factor for unintended pregnancy and abortion across a
      variety of settings. Unintended pregnancy terminated through unsafe abortion can
      result in death or serious complications. Therefore, reducing IPV can
      significantly reduce risks to maternal and reproductive health.

PMID- 22959632
TI  - Nelumbo nucifera leaf extract inhibits neointimal hyperplasia through modulation
      of smooth muscle cell proliferation and migration.
AB  - OBJECTIVE: Endovascular injury induced by balloon withdrawal leads to the
      increased activation of matrix metalloproteinases (MMPs) in the vascular wall
      allowing the proliferated smooth muscle cells (SMCs) to digest the surrounding
      extracellular matrix and migrate from the media into the intima leading to the
      intimal thickening. The objective of this study was to examine the effect of
      Nelumbo nucifera leaf extract (NL) on intimal thickening of rat carotid artery
      injured by balloon catheter and on the proliferation and migration of cultured
      vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-alpha.
      METHODS: NL was administered orally using gastric sonde at three different doses,
      100 mg kg(-1) (NL100), 400 mg kg(-1) (NL400), and 800 mg kg(-1) (NL800) for 4 wk
      from the day of balloon injury in the rats. VSMC proliferation and migration were
      assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and
      Boyden chamber methods, whereas enzymatic action of matrix metalloproteinase-2
      and -9 (MMP-2 and MMP-9) was carried out by gelatin zymography, and MMP-9 protein
      expression, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal
      kinase phosphorylations were assessed by Western blot analyses. RESULTS: NL
      reduced the intimal thickening by suppressing VSMC's proliferation through
      inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and their
      migration by reducing the expression of MMP-2 and -9 through inhibition of JNK1/2
      phosphorylation. CONCLUSION: Thus, the results suggest that NL can be considered
      of therapeutic value in the prevention of atherosclerosis because restenosis
      after percutaneous transluminal coronary angioplasty can be considered a model of
      "accelerated atherosclerosis."

PMID- 22959633
TI  - Waist circumference, but not body mass index, is a predictor of ventricular
      remodeling after anterior myocardial infarction.
AB  - OBJECTIVE: The impact of obesity on ventricular remodeling after myocardial
      infarction (MI) is still poorly understood. Therefore, the aim of this study was
      to evaluate the role of waist circumference (WC) and body mass index as
      predictors of cardiac remodeling in patients after an anterior MI. METHODS:
      Eighty-three consecutive patients with anterior MI were prospectively evaluated.
      Clinical characteristics and echocardiographic data were analyzed at admission
      and at a 6-mo follow-up. Ventricular remodeling was defined as a 10% increase in
      left ventricular end-systolic or end-diastolic diameter at the 6-mo follow-up.
      RESULTS: In our study, 83 consecutive patients were evaluated (72% men).
      Ventricular remodeling was present in 31% of the patients (77% men). Patients
      with remodeling had higher creatine phosphokinase and creatine phosphokinase-MB
      peak values, a higher resting heart rate, a larger left atrial diameter, and a
      larger interventricular septum diastolic thickness. In addition, patients with
      remodeling had lower peak velocity of early ventricular filling deceleration time
      and ejection fraction. Patients with remodeling presented higher WC values (with
      remodeling, 99.2 +/- 10.4 cm; without remodeling, 93.9 +/- 10.8 cm, P = 0.04),
      but there were no differences in the body mass index values. In the logistic
      regression analysis, WC, adjusted by age, gender, ejection fraction, and creatine
      phosphokinase levels, was an independent predictor of left ventricular remodeling
      (odds ratio 1.067, 95% confidence interval 1.001-1.129, P = 0.02). CONCLUSION:
      Waist circumference, but not body mass index, is a predictor of ventricular
      remodeling after an anterior MI. Therefore, the WC of these patients should be
      measured in clinical practice.

PMID- 22959634
TI  - Increased plasma availability of L-arginine in the postprandial period decreases
      the postprandial lipemia in older adults.
AB  - OBJECTIVE: Older adults have exaggerated postprandial lipemia, which increases
      their risk for cardiovascular disease. We sought to determine the effects of
      increased plasma L-arginine (L-ARG) availability on the oxidation of ingested fat
      (enriched with [1,1,1-(13)C]-triolein) and plasma triacylglycerol (TG)
      concentrations during the postprandial period in older subjects. METHODS: On one
      day, eight healthy subjects (67.8 +/- 1.3 y old) received an intravenous infusion
      of L-ARG during the first hour of the postprandial period (L-ARG trial), while on
      a separate day, and in a randomized order, they received saline (control trial).
      RESULTS: The 8-h area under the plasma concentration-time curve describing the
      postprandial plasma TG concentrations was considerably lower in the L-ARG trial
      than in the control trial (-4 +/- 21 versus 104 +/- 21 mg ? dL(-1) ? h(-1), P <
      0.01). The rate of the postprandial oxidation of the ingested lipid was not
      different between the trials, but the average contribution of the ingested oleate
      to the oleate of the TG of the plasma small TG-rich lipoproteins (Svedberg
      flotation index 20-400) was lower in the L-ARG trial (11 +/- 1 versus 18 +/- 2%,
      P < 0.01). L-ARG infusion also decreased the 8-h area under the plasma
      concentration-time curve of the plasma free fatty acid concentrations derived
      from the ingested fat compared with the saline infusion (0.77 +/- 0.09 versus
      1.11 +/- 0.08; mmol ? L(-1) ? h(-1), P < 0.01). CONCLUSION: Increasing the plasma
      L-ARG availability during the postprandial period decreases the postprandial
      lipemia in older adults, in association with a decrease in the postprandial
      contribution of ingested lipids into TGs of the plasma small TG-rich
      lipoproteins.

PMID- 22959635
TI  - Adolescent contraception. Foreword.

PMID- 22959636
TI  - Adolescent contraception: review and guidance for pediatric clinicians.
AB  - The objectives of this article are to review current contraceptive methods
      available to adolescents and to provide information, guidance, and encouragement
      to pediatric clinicians to enable them to engage in informed up-to-date
      interactions with their sexually active adolescent patients. Pregnancy prevention
      is a complex and dynamic process, and young people benefit from having a reliable
      authoritative source for information, counseling, and support. Clinicians who
      provide services for adolescents have a responsibility to develop their skills
      and knowledge base so that they can serve as that source. This review begins with
      a discussion about adolescent sexuality and pregnancy in the context of the
      adolescent developmental stages. We discuss approaches to introduce the topic of
      contraception during the clinic visit and contraceptive counseling techniques to
      assist with the discussion around this topic. In addition, information is
      included regarding confidential services, support of parental involvement, and
      the importance of male involvement in contraception. The specific contraceptive
      methods are reviewed in detail with the adolescent patient in mind. For each
      method, we discuss the mechanism of action, efficacy, contraindications, benefits
      and risks from the medical perspective, advantages and disadvantages from the
      patient's perspective, side effects, patient adherence, patient counseling, and
      any medication interactions. Furthermore, we have included a section that focuses
      on the contraceptive management for the adolescent patient with a disability
      and/or chronic illness. The article concludes with an approach to frequently
      asked or difficult questions. This section largely summarizes subsections on
      specific contraceptive methods and can be used as a quick reference on
      particularly challenging topics. Finally, a list of useful contraceptive
      management resources is provided for both clinicians and patients.

PMID- 22959637
TI  - Clinical ethical considerations in contraceptive care for teens.

PMID- 22959638
TI  - Experimental infection with the small intestinal trematode, Haplorchis pumilio,
      in young dogs.
AB  - Fishborne zoonotic trematodes (FZT) are highly prevalent in Southeast Asia.
      Recent studies on the role of domestic animals in the transmission of FZT in
      Northern Vietnam found that dogs, mainly infected with Haplorchis pumilio,
      contributed widely to the transmission of FZT. On this background, we conducted
      an experimental infection with H. pumilio to elucidate population dynamics and
      host reactions in dogs. Eight household-reared dogs (3-6 months old), were each
      orally infected with 500 H. pumilio metacercariae obtained by artificial
      digestion of naturally infected fish. Another eight dogs were included as
      uninfected controls. Faecal examination for eggs was performed twice weekly using
      a sieving and sedimentation technique. Body temperature and weight of the dogs
      were measured as was total white blood cells, blood eosinophils and packed cell
      volume. Subsets of dogs were examined post-mortem for presence of adult FZT at
      three different time points post infection by sectioning of the small intestine
      and caecum into four parts. Patent infections established in all eight infected
      dogs. The worm establishment ranged from 15 to 121 flukes (3-24%, mean 12%).
      Faecal egg excretion was measured in all eight infected dogs but no more than two
      eggs per g faeces (epg) were found at any time. Infections lasted for at least
      two months as documented by the presence of adult flukes in all three dogs
      necropsied on day 58 post infection. The predilection site of the flukes was
      identified as the lower part of jejunum (93% of total worm burden). The results
      of the haematological tests did not differ between the infected and uninfected
      group. Further, no clinical symptoms were observed in the infected group and no
      macroscopic pathological changes could be assigned to the trematode infections,
      neither did histopathological examination of the intestine reveal any differences
      between the infected and the control dogs. This study provides the first basic
      knowledge on the establishment, duration and location of H. pumilio infection in
      dogs. However, before any control measures can be recommended, knowledge
      regarding infection dynamics, epidemiology, health impact and control is needed.

PMID- 22959639
TI  - Single nucleotide polymorphisms in the bovine genome are associated with the
      number of oocytes collected during ovum pick up.
AB  - The number of follicles recruited in each estrous cycle has gained practical
      importance in artificial reproductive technology, as it determines the oocyte
      yield from ultrasound-guided ovum pickup for in vitro embryo production. We aimed
      to identify single nucleotide polymorphisms (SNPs) in bovine genes related to
      reproductive physiology and evaluate the association between the candidate SNPs
      and the number of oocytes collected from ultrasound-guided ovum pickup. We
      sequenced genomic segments of GDF9, FGF8, FGF10 and BMPR2 and identified
      seventeen SNPs in the Bos taurus and Bos indicus breeds. Two SNPs cause amino
      acid changes in the proteins GDF9 and FGF8. Three SNPs in GDF9, FGF8 and BMPR2
      were genotyped in 217 Nelore cows (B. indicus), while two previously identified
      mutations in LHCGR and mitochondrial DNA (mtDNA) were genotyped in the same
      group. The polymorphisms in GDF9, FGF8, BMRP2 and LHCGR were significantly
      associated (P<0.01) with the number of oocytes collected by ovum pickup, whereas
      the SNP in the mtDNA was not. In addition, we estimated an allelic substitution
      effect of 1.13+/-0.01 (P<0.01) oocytes for the SNP in the FGF8 gene. The results
      we report herein provide further evidence to support the hypothesis that genetic
      variability is an important component of the number of antral follicles in the
      bovine ovary.

PMID- 22959640
TI  - Morphological and morphometrical characterization, and estimation of population
      of preantral ovarian follicles from senile common squirrel monkey (Saimiri
      sciureus).
AB  - The experiment described the morphological and morphometrical characteristics as
      well as estimate the population of primordial, primary and secondary ovarian
      follicles from common squirrel monkey (Saimiri sciureus). Ovaries (n=10) from
      five senile squirrel monkeys were collected after natural death and processed for
      classical histology. The mean ovarian population was estimated as 915.04 +/-
      78.83, 230.46 +/- 20.82 and 115.88 +/- 15.72 primordial, primary and secondary
      follicles per ovary, respectively. 73.30% were classified as primordial, 18.62%
      as primary, and 8.09% as secondary follicles. From all these developmental
      stages, the mean diameters of follicles, oocytes, oocytes nuclei and the mean
      number of granulosa cells were described. The number of granulosa cells
      surrounding normal primordial follicles (5.65 +/- 0.001) was lower (P<0.05) than
      the number of granulosa cells (13.17 +/- 0.02) surrounding the primary follicles.
      Secondary follicles presented the highest (P<0.001) number of granulosa cells
      surrounding each oocyte (273.73 +/- 20.80). We have estimated the follicular
      population, as well as described the morphometric and morphological
      characteristics of preantral follicles from senile squirrel monkeys, which may be
      a valuable animal model for female ovarian aging studies.

PMID- 22959642
TI  - Arthroscopy of the elbow joint: A cadaveric study of portal placement.
AB  - Sixteen fresh cadaver elbows were examined by arthroscopy and dissection to
      evaluate the usefulness and the anatomic relationships of seven previously
      described portals for elbow arthroscopy. Most of the examined portals were found
      to be relatively close to neurovascular structures. The nerves that were found to
      be located closest to the portals were the posterior antebrachial cutaneous nerve
      at the direct lateral and antero-lateral portals, the radial nerve at the antero
      lateral portal, and the medial antebrachial cutaneous nerve at the high and low
      antero-medial portals. The degree of flexion and fluid distension of the joint
      were found to influence the position of nerves and vessels in relation to the
      arthroscopy portals. At least three different portals were found to be required
      for thorough examination of the elbow joint. The combination of the low postero
      lateral, the direct lateral, and the high antero-medial portals provided the
      largest visualized area.

PMID- 22959643
TI  - The source of shoulder pain in rheumatoid arthritis: Usefulness of local
      anesthetic injections.
AB  - Clinical symptoms and radiologic appearances are often poor indicators of the
      source of pain in the shoulder joint complex in patients with rheumatoid
      arthritis. In 75 rheumatoid shoulders, injections of 1 ml of 1 % local anesthetic
      were placed in the acromioclavicular joint, the subacromial bursa, and the
      glenohumeral joint, following a standard sequence. Forty-one shoulders were
      relieved of pain from subacromial or acromioclavicular injections even when there
      were advanced radiologic changes in the glenohumeral joint. However, if the
      sphericity of the humeral head had been lost, an injection of the glenohumeral
      joint usually confirmed this site as the source of pain. The results of local
      anesthetic injections allow decisions to be made about the most appropriate form
      of surgical or nonsurgical treatment.

PMID- 22959644
TI  - Extra-glenohumeral joint shoulder surgery in rheumatoid arthritis: The role of
      bursectomy, acromioplasty, and distal clavicle excision.
AB  - Twenty-four painful shoulders in patients with rheumatoid arthritis have been
      studied before and after extra-glenohumeral joint surgery. Preoperative local
      anesthetic injections were used to localize sites of pain and served as a basis
      for the surgical procedure performed. Radiographs were graded with the Larsen
      classification; 17 shoulders had radiographic evidence of advanced glenohumeral
      disease. Surgery included subacromial bursectomy, anterior acromioplasty, and
      excision of the outer end of the clavicle. At an average follow-up of 30 months
      (range 18 to 50 months) for 22 of the shoulders, 19 had minimal pain. Average
      motions improved in flexion from 68 degrees  to 121 degrees  and in external
      rotation from 23 degrees  to 52 degrees . Two experienced infections, one
      superficial and one deep. One further operation has been necessary to treat the
      shoulder arthritis. Extra-glenohumeral joint surgery, planned according to the
      results of preoperative injection testing, has a useful role in management of the
      shoulder in rheumatoid arthritis, even when the glenohumeral joint is involved
      radiographically.

PMID- 22959641
TI  - Cytokine-induced cytokine production by conventional and innate lymphoid cells.
AB  - Innate immune and differentiated T cells produce signature cytokines in response
      to cytokine stimulation. Optimal production requires stimulation by an NF-kappaB
      inducer, most commonly an interleukin (IL)-1 family member, and a STAT activator.
      Usually, there is linkage between the IL-1 family member, the activated STAT and
      the cytokines produced: IFNgamma producers respond to the IL-1 family member, IL
      18 and IL-12, a STAT4 activator; IL-13 producers respond to IL-33 (although for
      ILC2 cells this may be replaced by IL-25) and STAT5 activators; for cells
      producing IL-17A or IL-22, the combination is IL-1 and a STAT3 inducer. Cytokine
      induced cytokine production may have broad significance in orchestrating innate
      responses to distinct infectious agents and in maintaining inflammatory responses
      after elimination of the inciting antigen.

PMID- 22959645
TI  - Management of rotator cuff tears: A comparison of arthroscopic debridement and
      surgical repair.
AB  - In a prospective study, 87 consecutive patients with 88 chronic, full-thickness
      tears of the rotator cuff were randomly assigned to either open surgical tendon
      repair and anterior acromioplasty (50 shoulders) or arthroscopic debridement and
      subacromial decompression (38 shoulders). All patients were reexamined 2 to 5
      years after the operation with the University of California at Los Angeles 35
      Point Scale for Pain and Function of the Shoulder. The average ratings were 30.5
      (rotator cuff repair) and 25.1 (arthoscopic debridement/decompression) for each
      group. The open surgical repair group faired significantly better than the
      arthroscopic debridement group (p = .0028). Thirteen required subsequent
      procedures, four with tendon repair and nine with decompression. Five in the
      decompression group experienced cuff tear arthropathy. Surgical repair of full
      thickness rotator cuff tears provided results superior to those of arthroscopic
      debridement and subacromial decompression.

PMID- 22959646
TI  - Histologic and biomechanical characteristics of the supraspinatus tendon:
      Reference to rotator cuff tearing.
AB  - A bursal- or joint-side incomplete thickness tearing of the rotator cuff is
      clinically important, because it is known that this tearing has the potential to
      develop into a complete tendon disruption. Normal cadaveric supraspinatus tendons
      were analyzed histologically and biomechanically to clarify the differences in
      pathomechanical causation of bursal- and joint-side incomplete tears.
      Histologically, the bursal-side layer was composed of tendon bundles with a
      decreasing muscular component toward the insertion. The joint-side layer was a
      complex of tendon, ligament, and joint capsule without transitional areas.
      Biomechanically, the bursal-side layer had greater deformation and tensile
      strength. When each layer was divided into three portions of equal length, the
      middle segment of the bursal-side layer elongated the most, whereas the entire
      joint-side layer increased evenly in length. We conclude that the joint-side
      layer is more vulnerable to a tensile load than the bursal-side layer.

PMID- 22959647
TI  - Alterations in the supraspinatus muscle belly with rotator cuff tearing:
      Evaluation with magnetic resonance imaging.
AB  - We studied the supraspinatus muscle in patients with full-thickness rotator cuff
      tearing by analyzing its architecture on magnetic resonance imaging. Forty-six
      shoulders with rotator cuff tears requiring surgical repair were scanned parallel
      to the long axis of the supraspinatus muscle. We calculated the ratio of the
      largest width of the supraspinatus muscle belly to the distance from the greater
      tuberosity to the proximal end of the supraspinatus muscle. We classified the
      linear bands in the supraspinatus muscle, variation in its signal intensity, and
      irregularity and vagueness of its margins. The larger the rotator cuff tear, the
      more atrophic the supraspinatus muscle became. With increased atrophy, linear
      bands in the suprosupinotus muscle belly increased, muscle signal intensity
      became less uniform, and its margins became more irregular and vague.

PMID- 22959648
TI  - An anatomic study of the subscapular nerves: A guide for electromyographic
      analysis of the subscapularis muscle.
AB  - Fifty shoulders from 36 human cadavers were examined to identify the nerves
      innervating the subscapularis muscle and their point of entry into the muscle.
      Most of the specimens (82%) revealed three independent nerves to the
      subscapularis, 16% of the specimens demonstrated four nerves, and 2% of the
      shoulders demonstrated two nerves to the subscapularis. Variability was noted at
      the level of origin (division or cord) of each primary nerve branch to the
      muscle. The point of entry of each nerve into the subscapularis was measured from
      three clinical anatomic landmarks. The entry points were found to closely follow
      a line running parallel to the vertebral border of the scapula and inferior from
      the medial surface of the base of the coracoid. Previous electromyogram studies
      of the subscapularis have used one electrode to study its dynamic function. The
      anatomic data in this and other series suggest that multiple electrodes may be
      required for a complete electromyogram study of the subscapularis. The findings
      of this study facilitate the placement of two intramuscular fine wire electrodes
      for electromyogrophic analysis, which permits the investigation of the
      subscapularis muscle as two functional units.

PMID- 22959649
TI  - Secondary fracture of the humerus after closed reduction and percutaneous
      stabilization of a subcapital fracture.

PMID- 22959650
TI  - A plea for the humeral hood.

PMID- 22959651
TI  - An interview with Ming-Wei Wang.

PMID- 22959652
TI  - Current challenges in translational pain research.
AB  - The current gap between basic science research and the development of new
      analgesics presents a serious challenge for the future of pain medicine. This
      challenge is particularly difficult in the search for better treatment for
      comorbid chronic pain conditions because: (i) animal 'pain' models do not
      simulate multidimensional clinical pain conditions; (ii) animal behavioral
      testing does not assess subjective pain experience; (iii) preclinical data
      provide little assurance regarding the direction of new analgesic development;
      and (iv) clinical trials routinely use over-sanitized study populations and fail
      to capture the multidisciplinary consequences of comorbid chronic pain.
      Therefore, a paradigm shift in translational pain research is necessary to
      transform the current strategy from focusing on molecular switches of nociception
      to studying pain as a system-based integral response that includes psychosocial
      comorbidities. Several key issues of translational pain research are discussed in
      this review.

PMID- 22959653
TI  - Benefits and complications of the duodenal switch/biliopancreatic diversion
      compared to the Roux-en-Y gastric bypass.
AB  - BACKGROUND: Despite providing superb excess weight loss and increased resolution
      of comorbid diseases, such as type 2 diabetes mellitus, compared to other
      bariatric procedures, the duodenal switch/ biliopancreatic diversion (DS/BD) has
      not gained widespread acceptance among patients and physicians. In this study, we
      investigated outcomes, symptoms and complications among postsurgical DS patients
      compared to RYGB patients. METHODS: We used propensity scores to retrospectively
      match patients who underwent DS/BD between 2005 and 2010 to comparable Roux-en-Y
      gastric bypass (RYGB) patients. We then reviewed patient charts, and surveyed
      patients using the University of Minnesota Bariatric Surgery Outcomes Survey tool
      to track outcomes, comorbid illnesses and complications. RESULTS: One hundred
      ninety consecutive patients underwent primary DS/BD between 2005 and 2010 at the
      University of Minnesota Medical Center. There were 178 patients available for
      follow-up (93.7%) who were matched to 139 RYGB patients. Type 2 diabetes,
      hypertension, and hyperlipidemia all significantly improved in each group.
      Improvements were significantly higher in the DS/BD group. Percent total weight
      loss was not different between groups. Loose stools and bloating symptoms were
      more frequently reported among DS/BD patients. With the exception of increased
      emergency department visits among DS/BD patients (P < .01), overall complication
      rates were not significantly different between DS/BD and RYGB. There was no
      difference in mortality rates between the groups. CONCLUSION: The DS/BD is a
      robust procedure that engenders both superior weight loss and improvement of
      major comorbidities. Complication and adverse event rates are similar to those of
      RYGB.

PMID- 22959654
TI  - Insight into mechanism of in vitro insulin secretion increase induced by
      antipsychotic clozapine: role of FOXA1 and mitochondrial citrate carrier.
AB  - The use of clozapine and other antipsychotic drugs is known to be associated with
      a number of adverse metabolic side effects, including diabetes mellitus. These
      side effects could be, at least in part, the result of impaired islet cell
      function and abnormal insulin secretion, although the underlying mechanisms are
      unknown. The aim of this study is the identification of targets for clozapine
      related to the abnormal insulin secretion. We identify a specific activation of
      the transcriptional factor FOXA1, but not FOXA2 and FOXA3, by clozapine in HepG2
      cells. Clozapine enhances FOXA1 DNA-binding and its transcriptional activity,
      increasing mitochondrial citrate carrier gene expression, which contains a FOXA1
      site in its promoter. Haloperidol, a conventional antipsychotic drug, does not
      determine any increase of FOXA1 gene expression. We also demonstrate that
      clozapine upregulates FOXA1 and CIC gene expression in INS-1 cells only at basal
      glucose concentration. In addition, we find that abnormal insulin secretion in
      basal glucose conditions could be completely abolished by FOXA1 silencing in INS
      1 cells treated with clozapine. The identification of FOXA1 as a novel target for
      clozapine may shed more light to understand molecular mechanism of abnormal
      insulin secretion during clozapine treatment. 

PMID- 22959655
TI  - Antibiotic susceptibility testing in early and chronic respiratory infections
      with Pseudomonas aeruginosa.

PMID- 22959656
TI  - Variation in concentrations of three mercury (Hg) forms at a rural and a suburban
      site in New York State.
AB  - Tekran(r) Hg speciation systems were used at a rural site (Huntington Forest, NY;
      HF) and a suburban site (Rochester, NY; ROC) to measure gaseous elemental mercury
      (GEM), gaseous oxidized mercury (GOM), and fine particulate-bound mercury
      (PBM2.5) concentrations for two years (December 2007 to November 2009). Ancillary
      data were also available from the New York State Department of Environmental
      Conservation and the United States Environmental Protection Agency Clean Air
      Status and Trends Network. Seasonal GEM concentrations were similar at both sites
      and influenced by factors such as the planet boundary layer (PBL) height and
      mercury emissions from snow, soil, and point sources. In some seasons, O3 was
      negatively correlated with GEM at ROC and positively correlated with GEM at HF.
      At HF, O3 was correlated with GOM and was typically higher in the afternoon. The
      cause of this pattern may be photochemical reactions during the day, and the GOM
      diel pattern may also be due to deposition which is enhanced by dew formation
      during the night and early morning. PBM2.5 concentrations were higher in winter
      at both sites. This is indicative of local wood combustion for space heating in
      winter, increased sorption to particles at lower temperatures, and lower PBL in
      the winter. At the suburban site, 2 of 12 events with enhanced GEM/CO ratios were
      poorly correlated with SO2/GOM, implying that these two events were due either to
      long range transport or regional metallurgical industries in Canada.

PMID- 22959657
TI  - Establishing a universal swabbing and clean-up protocol for the combined recovery
      of organic and inorganic explosive residues.
AB  - A single-step solvent extraction and a solid-phase extraction (SPE) clean-up
      procedure was developed and optimised in order to establish a universal sampling
      and clean-up protocol for the combined recovery of organic and inorganic
      explosive residues. Mixtures of three common swabbing solvents (acetone,
      acetonitrile and methanol) with water, in various ratios, were assessed for the
      extraction of four target organic explosives [pentaerythritol tetranitrate
      (PETN), 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX) and triacetone triperoxide (TATP)] and two inorganic anions (chlorate and
      nitrate) from alcohol wipes that were used as a swabbing medium. An efficient,
      single-step extraction of both organic and inorganic compounds from the wipes was
      achieved using 60% v/v methanol/water. To develop a clean-up procedure, four
      commercially available SPE cartridges (Oasis HLB, Isolute((r)) C18, Bond
      Elut((r)) ENV and ABS ELUT Nexus) and an in-house packed XAD-7 cartridge were
      firstly evaluated for their retention capacity toward three organic explosives
      (PETN, TNT and RDX) in a mixture of methanol and water. A SPE technique was then
      developed and optimised from the short-listed sorbents with four representative
      organic explosives (including TATP). The Nexus cartridge was found to provide a
      suitable sorbent for extract clean-up following swab extraction with 60% v/v
      methanol/water. By incorporating the optimised clean-up procedure with the
      application of a polyester-based alcohol wipe as a sampling medium, a universal
      swabbing protocol for the combined recovery of both organic and inorganic
      explosive residues was established. The feasibility of the proposed protocol was
      assessed by collection and quantitation of the residue from a mixture of TNT,
      PETN and chlorate deposited on a laminate test surface.

PMID- 22959658
TI  - Automatic brain caudate nuclei segmentation and classification in diagnostic of
      Attention-Deficit/Hyperactivity Disorder.
AB  - We present a fully automatic diagnostic imaging test for Attention
      Deficit/Hyperactivity Disorder diagnosis assistance based on previously found
      evidences of caudate nucleus volumetric abnormalities. The proposed method
      consists of different steps: a new automatic method for external and internal
      segmentation of caudate based on Machine Learning methodologies; the definition
      of a set of new volume relation features, 3D Dissociated Dipoles, used for
      caudate representation and classification. We separately validate the
      contributions using real data from a pediatric population and show precise
      internal caudate segmentation and discrimination power of the diagnostic test,
      showing significant performance improvements in comparison to other state-of-the
      art methods.

PMID- 22959659
TI  - Prognostic factors in patients with advanced renal cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate prognostic factors in
      patients with RCC. MATERIALS AND METHODS: The expression of several biomarkers
      were measured by immunohistochemistry (IHC), together with 2 analytic factors
      (thrombocytosis and neutrophilia), in 135 patients with advanced RCC treated with
      new targeted drugs (NTDs) (n = 67) and/or cytokines (CKs) (n = 68)-with 23 of the
      patients who received CKs also receiving NTDs-between July 1996 and February
      2010. Relationships with overall survival (OS) and progression-free survival
      (PFS) were searched for. RESULTS: Univariate statistical analysis revealed that
      high expression of hypoxia-inducible factor-1alpha (HIF-1alpha) correlated with
      poor prognosis in NTD treatment (PFS, 5.4 vs. 13.5, low expression months; P =
      .033) and CK treatment (PFS, 3.3 vs. 5.7, low expression; P = .003).
      Overexpression of carbonic anhydrase IX (CAIX) was associated with better
      prognosis with NTD treatment (OS, 32.1 vs. 7.8 months; P < .001) and CK treatment
      (OS, 32.9 vs. 5.9 months; P = .001). Positive PTEN was related to good prognosis
      with sunitinib (PFS, 15.1 vs. 6.5 months; P = .003) and CKs (OS, 13.7 vs. 7.9
      months; P = .039). Increased expression of p21 was related to poor prognosis with
      NTD treatment (PFS, 5.9 vs. 16.8 months; P = .024) and CK treatment (PFS, 3.9 vs.
      7.5 months; P < .001) Thrombocytosis was related to poor prognosis with NTDs (OS,
      15.9 vs. 26.7 months; P = .007) and CKs (OS, 5.9 vs. 14.3 months; P = .010).
      Neutrophilia was related to poor prognosis with NTDs (OS, 17.6 vs. 25.4 months; P
      = .063) and CKs (OS, 5.9 vs. 12.8 months; P = .035). Multivariate analysis
      revealed that overexpression of CAIX was a favorable prognostic factor
      independent of PFS (hazard ratio [HR], 0.107; P < .001) and OS (HR, 0.055; P <
      .001). CONCLUSIONS: HIF-1alpha, PTEN, p21, thrombocytosis, neutrophilia, and CAIX
      in particular are useful prognostic factors in patients with advanced RCC.

PMID- 22959660
TI  - Geographic variation in inquest rates in Australia.
AB  - This paper examines the relationship between the remoteness of locations in which
      deaths occur and coroners' decisions to hold inquests. We analysed 16,242 deaths
      investigated by coroners in three Australian states over 7.5 yrs. We used a
      choropleth map to show inquest rates in each remoteness locality (excluding
      deaths for which inquests were mandated by statute). We then used adjusted
      logistic regression to assess the association between the remoteness of a death's
      location and the odds coroners would select it for investigation by inquest. We
      found the remoteness of a death's location strongly and positively predicts the
      chance that an inquest will be held. Like analogous findings in the delivery of
      health services, this small-area variation in legal decision making raises
      questions of appropriateness.

PMID- 22959661
TI  - Review of highway runoff characteristics: comparative analysis and universal
      implications.
AB  - This review interprets highway runoff characterization studies performed on
      different continents. The results are synthesized to discuss the historical
      trends, first flush effects of pollutants, pollutant form as dissolved vs.
      particulate, and to identify surrogate water quality parameters. The information
      presented in this review showed that: (1) variability has been observed in all
      quality parameters from each continent and among continents; (2) with a few
      exceptions the variability seems to be within the expected range; (3)
      inconsistent monitoring data as well as inconsistent quality assurance and
      quality control measures were reported among studies, which may be partially
      responsible for variability of water quality results; (4) compared with historic
      data, the concentration of total Pb decreased exponentially, which can mostly be
      credited to leaded gasoline phase-out regulation; (5) first flush effects of
      pollutants based on concentration have been reported consistently (however, mass
      first flush effects for pollutants have been reported inconsistently compared
      with concentration first flush effect); (6) most metal pollutants and phosphorus
      are present in both the particulate and dissolved forms; and (7) strong
      correlations were observed between TSS, TDS, TOC and iron (Fe) and 13 other
      constituents and water quality parameters (turbidity, O&G, TPH, DOC, TKN, EC, Cl,
      Cd, Cr, Cu, Ni, Pb, Zn).

PMID- 22959662
TI  - Liver fat content is associated with an increase in cholesterol synthesis
      independent of statin therapy use in patients with type 2 diabetes.
AB  - We investigated how liver fat content (LFC) influences cholesterol metabolism by
      quantifying liver fat using proton magnetic resonance spectroscopy and by
      measuring the serum concentrations of lathosterol, a marker of cholesterol
      synthesis, and sitosterol and campesterol, two markers of cholesterol absorption.
      We also evaluated whether this relationship could be modified by statin therapy.
      The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%)
      received statin therapy. RESULTS: One hundred and sixty-five patients (62.7%) had
      steatosis (LFC>5.5%). We performed specific analyses in patients without statin
      therapy and in patients treated with statin therapy. In both groups, the
      lathosterol to cholesterol ratio correlated positively with LFC, and in
      multivariate analysis, the lathosterol to cholesterol ratio was associated with
      LFC independently of age, gender and BMI. Sitosterol and campesterol
      concentrations were not associated with LFC. CONCLUSIONS: Our study suggests that
      in patients with type 2 diabetes, LFC is associated with an increase in
      cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin
      therapy does not modify this relationship.

PMID- 22959663
TI  - Changes in lipid transport-involved proteins of epicardial adipose tissue
      associated with coronary artery disease.
AB  - OBJECTIVE: Recent studies have focused on the potential role of epicardial
      adipose tissue (EAT) in the physiopathology of several metabolic and
      cardiovascular diseases, especially coronary artery disease (CAD). We aimed to
      study whether there are differences in the proteome and the secretome between
      epicardial and subcutaneous adipose tissue (SAT) from patients with and without
      CAD. METHODS: EAT and SAT samples were collected from 64 patients undergoing
      elective cardiac surgery either for coronary artery bypass grafting or valve
      surgery. One or two-dimensional electrophoresis were performed on tissue samples
      and media collected at 3, 6, 24 or 48 of tissue culture. Protein identification
      was performed with mass spectrometry, and the results were then validated with
      Western blot or enzyme immunoassay. mRNA expression levels were analysed by real
      time polymerase chain reaction. RESULTS: The release of several proteins was
      found to be higher in EAT that in SAT. Remarkably, there were higher levels of
      apolipoprotein A-I and glutation S-transferase P release, whereas mRNA expression
      of fatty acid binding protein 4 was lower in EAT. Although apolipoprotein A-I
      protein quantity in EAT was similar between CAD and non CAD patients, its
      released levels from this fat pad were lower in CAD. CONCLUSION: EAT and SAT show
      different profiles of protein release and a different pattern was also found in
      samples from patients with CAD. These findings might support the hypothesis that
      EAT plays an interesting role in the physiopathology of atherosclerosis and CAD.

PMID- 22959665
TI  - Response to: "On Cardiovascular Risk Estimation in Patients With Psoriasis: The
      REGICOR and SCORE Scales"

PMID- 22959664
TI  - A prospective study of childhood social hardships and age at menarche.
AB  - PURPOSE: To determine the role of type, timing, and cumulative childhood
      hardships on age at menarche in a prospective cohort study. METHODS: A
      longitudinal analysis was undertaken of 4524 female participants of the National
      Child Development Study cohort (1958-2003). Six types of childhood hardships were
      identified with a factor analysis methodology. Paternal absence/low involvement
      in childhood was an a priori hardship. Retrospective reports of abuse in
      childhood also were explored in relation to age at menarche. Generalized logit
      regression analyses explored the impact of type, timing, and cumulative hardships
      on age at menarche (<= 11, 12-13, >= 14 years). RESULTS: Cumulative childhood
      hardships were associated with a graded increase in risk for later menarche with
      adjusted odds ratio [AOR] of 1.37 (95% confidence interval [95% CI], 1.10-1.70),
      1.50 (95% CI, 1.18-1.91), and 1.58 (95% CI, 1.29-1.92) among those with two,
      three, and four or more adversities, respectively. More than two hardships in
      early life had the strongest association with late menarche (AOR, 2.32; 95% CI,
      1.12-4.80). Sexual abuse was most strongly associated with early menarche (AOR,
      2.60; 95% CI, 1.40-4.81). CONCLUSIONS: Cumulative childhood hardships increased
      risk for later age at menarche. Child abuse was associated with both early and
      late menarche, although associations varied by type of abuse.

PMID- 22959666
TI  - Clinical presentation of acral lentiginous melanoma: a descriptive study.
AB  - BACKGROUND AND OBJECTIVE: Acral lentiginous melanomas -the melanomas most
      commonly found on the distal portions of the limbs- have usually reached more
      advanced stages than other types of melanoma when diagnosed. Our aim was to
      describe the clinical presentation of these tumors. MATERIALS AND METHODS:
      Retrospective, descriptive, observational study of cases recorded in the database
      of the Instituto Valenciano de Oncologia. In telephone interviews the patients
      answered a questionnaire on the presenting features of the lesion, on the
      presence of signs and symptoms included in the Glasgow 7-point checklist and the
      ABCDEs of melanoma, and on diagnostic delay attributable to patient or physician.
      RESULTS: In the interviews with the 23 patients who responded to the
      questionnaire, we detected a diagnostic delay of more than 1 year attributable to
      the patient (delay in seeking care) in 30.4% of the cases. Diagnostic delay of
      more than 1 year attributable to the physician (failure to suspect the diagnosis)
      was identified in 20%. The most frequent reasons for consulting a physician about
      a lesion were changes in size, changes in color, bleeding, or failure to heal. In
      20% of the cases the evaluating physician did not order histology for over a
      year. CONCLUSIONS: Diagnostic delay is a significant problem in acral lentiginous
      melanoma and may be attributable either to patients or to physicians' failure to
      recognize warning signs. Melanoma prevention campaigns should place more emphasis
      on the possibility of melanomas appearing on the palms and, particularly, on the
      soles.

PMID- 22959668
TI  - Reliable porcine coronary model of chronic total occlusion using copper wire
      stents and bioabsorbable levo-polylactic acid polymer.
AB  - BACKGROUND: Chronic total occlusion (CTO) remains a challenge in interventional
      cardiology. We investigated the feasibility and reliability of copper wire stents
      and levo-polylactic acid (l-PLA) as a means of CTO induction in a porcine model.
      METHODS AND RESULTS: In one group of 20 swine, copper stents were crimped on a
      3.0mm angioplasty balloon and inserted into the mid-left anterior descending
      coronary artery (LAD). In the other group of 20 swine, l-PLA was wrapped on a
      guidewire and pushed into the distal LAD with a 3.0mm balloon catheter to induce
      embolization. Of 20 swine which underwent copper stent implantation, 13 died of
      stent thrombosis. In the remaining 7 swine, total or near total occlusion with
      collateral circulation was observed at 5 weeks. Of 20 swine which underwent l-PLA
      embolization, 4 died of ventricular fibrillation during or shortly after the
      procedure. Serial histopathologic studies showed complete absorption of the
      polymer with replacement by fibrotic tissue approximately 4 weeks following the
      polymer implantation. CONCLUSIONS: CTO could be reliably induced in porcine
      coronary arteries by copper stents and l-PLA. These models may support
      investigation of new percutaneous devices to facilitate CTO interventions.

PMID- 22959670
TI  - A vitamin for the brain.
AB  - In the central nervous system (CNS) the function of retinoic acid, the active
      metabolite of vitamin A, is best understood from its action in guiding embryonic
      development; as development comes to completion, retinoic acid signaling
      declines. However, it is increasingly recognized that this signaling mechanism
      does not disappear in the adult brain but becomes more regionally focused and
      takes on new roles. These functions are often tied to processes of neural
      plasticity whether in the hippocampus, through homeostatic neural plasticity, the
      olfactory bulb or the hypothalamus. The role of retinoic acid in the control of
      plastic processes has led to suggestions of its involvement in neural disorders,
      both degenerative and psychiatric. This review presents a snapshot of
      developments in these areas over recent years.

PMID- 22959671
TI  - From me to we: transforming values and building professional community through
      narratives.
AB  - Entering high acuity environments for the first time is a daunting experience for
      nursing students and new graduates. They are challenged to be both highly skilled
      and critical thinkers. In addition, because of increasing acuity and the
      burgeoning prevalence of patients with long-term, multi-faceted health care
      issues, particularly in the elderly population, students also need advanced
      interpersonal communication skills. Nurse academics need to respond to these
      imperatives by examining the fundamental values of the profession so that they
      can provide learning opportunities that place equal emphasis on developing
      affective attributes alongside cognitive and psychomotor skills. This paper
      presents a novel values-based learning activity using transformative learning
      principles. Three extracts from a book were chosen that conveyed the uncertainty
      and insecurity that a novice Intensive care nurse overcame to become a competent,
      professional, trusted practitioner, her passion to be part of a caring profession
      and the positive role models who shaped her values. Transformative Learning
      questions were developed to promote critical reflection on the shared values of
      the profession and the transition from the personal to professional self.
      Students' insights from the activity focused on their aspirations to provide
      patient-centred care and included recognition of the emotional labour of caring,
      the need to rise above negative cultures, how to challenge out-dated practices
      and the importance of strengthening professional identity. Krathwohl et al.
      (1964) Stages of Affective Learning was used to evaluate the activity.

PMID- 22959669
TI  - Androgen receptor influences on body defense system via modulation of innate and
      adaptive immune systems: lessons from conditional AR knockout mice.
AB  - Upon insult, such as infection or tissue injury, the innate and adaptive immune
      systems initiate a series of responses to defend the body. Recent studies from
      immune cell-specific androgen receptor (AR) knockout mice demonstrated that
      androgen and its receptor (androgen/AR) play significant roles in both immune
      regulations. In the innate immunity, androgen/AR is required for generation and
      proper function of neutrophils; androgen/AR also regulates wound healing
      processes through macrophage recruitment and proinflammatory cytokine production.
      In adaptive immunity, androgen/AR exerts suppressive effects on development and
      activation of T and B cells. Removal of such suppression causes thymic
      enlargement and excessive export of immature B cells. Altogether, androgen/AR
      plays distinct roles in individual immune cells, and targeting androgen/AR may
      help in treatment and management of immune-related diseases.

PMID- 22959672
TI  - Nursing preceptorship experiences in rural settings: "I would work here for
      free".
AB  - AIMS: The primary aim was to capture the experience of preceptorship in a rural
      setting, via photographic narrative. It is hoped that this narrative will
      highlight areas that require greater support; communicate the experience of rural
      preceptorship for students, educators and policymakers; and emphasize the
      benefits of this experience for these current and future stakeholders. METHODS:
      In a photovoice study, preceptors (n = 4) and students (n = 4) in rural, Western
      Canadian health care settings were given digital cameras and asked to provide
      images and commentary about the experience of preceptorship. Participants
      selected the photographs to be included as data, and participated in thematic
      data analysis, through facilitated group discussions during and following the
      preceptorships. FINDINGS: This article explores the category of teaching and
      learning, encompassing three themes: confidence, conscientiousness, and mutual
      growth. Preceptors emphasized the importance of students bringing sufficient
      knowledge to the rural preceptorship, pertaining not only to the nature of care
      but also to the predominant health care issues in the community. IMPLICATIONS:
      The implications were generated in part by the participants, who indicated a need
      for more student practica in rural settings; curricular changes to incorporate
      knowledge about rural health care and communities; post-graduation rural
      mentorship programs; and site/community-specific preparation.

PMID- 22959673
TI  - Venus flytrap biomechanics: forces in the Dionaea muscipula trap.
AB  - Biomechanics of morphing structures in the Venus flytrap has attracted the
      attention of scientists during the last 140 years. The trap closes in a tenth of
      a second if a prey touches a trigger hair twice. The driving force of the closing
      process is most likely due to the elastic curvature energy stored and locked in
      the leaves, which is caused by a pressure differential between the upper and
      lower layers of the leaf. The trap strikes, holds and compresses the prey. We
      have developed new methods for measuring all these forces involved in the hunting
      cycle. We made precise calibration of the piezoelectric sensor and performed
      direct measurements of the average impact force of the trap closing using a high
      speed video camera for the determination of time constants. The new equation for
      the average impact force was derived. The impact average force between rims of
      two lobes in the Venus flytrap was found equal to 149 mN and the corresponding
      pressure between the rims was about 41 kPa. Direct measurements of the
      constriction force in the trap of Dionaea muscipula was performed during gelatin
      digestion. This force increases in the process of digestion from zero to 450 mN
      with maximal constriction pressure created by the lobes reaching to 9 kPa. The
      insects and different small prey have little chance to escape after the snap of
      the trap. The prey would need to overpower the "escaping" force which is very
      strong and can reach up to 4N.

PMID- 22959674
TI  - Characterization of a type-A response regulator differentially expressed during
      adventitious caulogenesis in Pinus pinaster.
AB  - The molecular cloning and characterization of PipsRR1, a type-A response
      regulator in Pinus pinaster, is reported here. Type-A response regulators mediate
      downstream responses to cytokinin and act as negative feedback regulators of the
      signal transduction pathway. Some type-A response regulators in Arabidopsis have
      been related to de novo meristem formation. However, little information exists in
      Pinus spp. The PipsRR1 gene contains 5 exons, as do all type-A response
      regulators in Arabidopsis, and the deduced protein contains a receiver domain
      with the conserved DDK residues and a short C terminal extension. Expression
      analysis showed that the PipsRR1 gene is differentially expressed during the
      first phases of adventitious caulogenesis induced by benzyladenine in P. pinaster
      cotyledons, suggesting that PipsRR1 plays a role in caulogenesis in conifers.
      Additionally, a binary vector carrying the PipsRR1 promoter driving GFP:GUS
      expression was constructed to analyze the promoter activity in P. pinaster
      somatic embryos. The results of genetic transformation showed GUS activity during
      somatic embryo mass proliferation and embryo maturation.

PMID- 22959675
TI  - The expression profiling of the CsPYL, CsPP2C and CsSnRK2 gene families during
      fruit development and drought stress in cucumber.
AB  - The abscisic acid (ABA) signal transduction core components in plants include the
      ABA receptors (PYR/PYL/RCARs), the group A type 2C protein phosphatases (PP2Cs)
      and the subclass III SNF1-related protein kinases 2 (SnRK2s). In this study, via
      homology cloning, three CsPYLs, four CsPP2Cs and two CsSnRK2s partial cDNAs were
      obtained in cucumber (Cucumis sativus). In silico analysis results indicated that
      all CsPYL, CsPP2C, and CsSnRK2 genes obtained are homologous to Arabidopsis
      AtPYL, AtPP2C, and AtSnRK2 genes, respectively. Based on phylogenetic analysis,
      only CsPP2C2 and CsSnRK2.2 belonged to group A PP2C and subclass III SnRK2,
      respectively, and may involve in ABA signal transduction. During cucumber fruit
      development and ripening, CsPYL2 and CsPP2C2 were highly expressed and both
      reached their peak value at 27 DAF, at which stage the ABA content was also at
      its highest level, which indicated that the CsPYL2 and CsPP2C2 may involve in
      transducing ABA signal in fruit and regulating fruit development and ripening.
      Under drought stress condition in cucumber seedlings, CsPYL1, CsPYL2, CsPP2C2 and
      CsSnKR2.2 were sensitive and up-regulated in root, stem and leaf; meanwhile,
      CsPYL3 showed a low sensitivity and were down-regulated in root and stem.

PMID- 22959676
TI  - Liquid chromatography-tandem mass spectrometry method for simultaneous
      determination of seven commonly used anticancer drugs in human plasma.
AB  - This paper describes the development and validation of a novel, general liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous
      determination of cyclophosphamide, ifosfamide, irinotecan, etoposide,
      gemcitabine, carboplatin and pemetrexed concentrations in human plasma. Samples
      were prepared by two kinds of extraction method and analyzed using a gradient
      separation over an Atlantis T3-C18 column (2.1 mm*100 mm, 3 MUm, Waters).
      Positive electrospray ionization was employed as the ionization source. The
      mobile phase consisted of acetonitrile-water (0.1% formic acid and 10mM ammonium
      acetate) at a flow rate of 0.25 mL/min. Linear coefficients of correlation were
      >0.992 for all analytes. The intra- and inter-day relative standard deviation
      across three validation runs over the entire concentration range was less than
      9.2%, while the accuracy was within +/- 10.5%. The mean recovery of all the
      analytes ranged from 50.0 to 81.0%. This method was successfully applied to
      clinical samples from cancer patients.

PMID- 22959677
TI  - MMP-2 concentrations in stroke according to etiology: adjusting for enzyme
      degradation in stored deep-frozen serum and other methodological pitfalls.
AB  - Matrix metalloproteinases (MMP) have a prominent role in the pathophysiology of
      stroke. We investigated potential differences in MMP-2 concentrations with
      respect to acute stroke etiology. For another MMP family member, MMP-9,
      significant degradation over time has been found even when stored at -80  degrees
      C, so we measured temporal degradation of MMP-2 and adjusted for this and other
      factors potentially affecting our results. For 264 patients with acute stroke at
      baseline and a control cohort of 120 subjects, MMP-2 concentrations were measured
      using commercially available enzyme-linked immunosorbent assay (ELISA) kits. For
      each stroke patient, stroke etiology was categorized as cardioembolic, large
      vessel or small vessel ischemic stroke, or primary hemorrhage. Stroke patients
      had significantly lower MMP-2 concentrations than controls (mean +/- standard
      deviation: 175.6 +/- 65.6 ng/mL versus 212.0 +/- 54.8 ng/mL, p<0.001). However,
      sample degradation (average sample storage time: 240.0 +/- 113.7 days) was
      considerable, amounting to approximately 15% per year. The full extent of
      differences in MMP-2 concentrations between stroke of different subtypes only
      became evident when results were adjusted for enzyme degradation during storage
      and other methodological pitfalls. Before adjustment, the only significant
      difference between etiologies was that the cardioembolic stroke group had a
      significantly higher concentration of MMP-2 than the hemorrhage group. After
      adjustment for time to analysis and ELISA plate clustering, patients with
      cardioembolic stroke had significantly higher MMP-2 concentrations in comparison
      to all other stroke subtypes.

PMID- 22959678
TI  - A pilot study of psychometric properties of the Beijing version of Montreal
      Cognitive Assessment in patients with idiopathic Parkinson's disease in China.
AB  - Cognitive dysfunction is one of the most critical clinical manifestations of
      Parkinson's disease (PD), and its accurate and efficient diagnosis is crucial for
      treatment. We evaluated the psychometric properties of the Beijing version of the
      Montreal Cognitive Assessment (BJ-MoCA) in 123 Chinese patients with idiopathic
      PD. The internal consistency and convergent validity of the BJ-MoCA were examined
      and psychometric characteristics of BJ-MoCA scores were analyzed in PD patients
      with ''normal'' Mini-Mental State Examination (MMSE) scores. More than half
      (56.9%) of the patients with normal MMSE scores showed cognitive impairment in
      multiple cognitive domains, including visuospatial and executive functions,
      naming, attention, language, delayed recall, and orientation. The impaired
      delayed recall was less likely to occur in newly diagnosed patients, and the
      orientation ability in patients with early onset was rarely affected. The
      multivariate regression analysis revealed that the age of symptom onset and
      disease severity were independent predictors of cognitive impairment. Thus, the
      current findings demonstrate that the BJ-MoCA is a reliable tool for screening
      cognitive dysfunction in Chinese patients with idiopathic PD. It is more
      sensitive than the MMSE for screening early cognitive decline in non-memory
      dysfunction.

PMID- 22959679
TI  - Killing and latent classes of PTSD symptoms in Iraq and Afghanistan veterans.
AB  - BACKGROUND: Our goal was to better understand distinct PTSD symptom presentations
      in Iraq and Afghanistan Veterans (N=227) and to determine whether those who
      killed in war were at risk for being in the most symptomatic class. METHODS: We
      used latent class analysis of responses to the PTSD checklist and logistic
      regression of most symptomatic class. RESULTS: We found that a four-class
      solution best fit the data, with the following profiles emerging: High Symptom
      (34% of participants), Intermediate Symptom (41%), Intermediate Symptom with Low
      Emotional Numbing (10%), and Low Symptom (15%). The largest group of individuals
      who reported killing (45%) was in the High Symptom class, and those who killed
      had twice the odds of being in the most symptomatic PTSD class, compared to those
      who did not kill. Those who endorsed killing a non-combatant (OR=4.56, 95% CI
      [1.77, 11.7], p<0.01) or killing in the context of anger or revenge (OR=4.63, 95%
      CI=[1.89, 11.4], p<0.001) were more likely to belong to the most symptomatic PTSD
      class, compared to those who did not kill. LIMITATIONS: The study was
      retrospective and cross-sectional. The results may not generalize to veterans of
      other wars. CONCLUSIONS: Killing in war may be an important indicator of risk for
      developing frequent and severe PTSD symptoms. This has implications for the
      mental healthcare of veterans, providing evidence that a comprehensive evaluation
      of returning veterans should include an assessment of killing experiences and
      reactions to killing.

PMID- 22959680
TI  - Screening for bipolar disorder in the primary care: a Brazilian survey.
AB  - BACKGROUND: Two recent studies conducted in the US and in France found an
      unexpectedly high prevalence of a positive screen for bipolar disorder (BD) in
      primary care (PC). There are few studies of the prevalence of BD in PC and no
      information exists on the epidemiology of BD in Brazilian PC services. This study
      investigated the prevalence and correlates of a positive screen for BD among
      patients attending three Brazilian PC centers. METHODS: This cross-sectional
      survey recruited a systematic sample of 720 patients between 18 and 70 years of
      age who were seeking primary care treatment. Study measures included the Mood
      Disorder Questionnaire, the Center for Epidemiologic Studies Depression Scale,
      the World Health Organization Quality of Life instrument-Abbreviated version, the
      Functional Comorbidity Index, the Functioning Assessment Short Test, data on past
      mental health care, service utilization and a review of medical records for coded
      diagnosis. RESULTS: The prevalence of receiving positive screen for BD was 7.6%
      (n=55; 95% CI: 5.6-9.5%), but only 2 (3.6%) were recognized by general
      practitioners. A positive screen for BD was associated with significant
      depressive symptoms (CES-D score >=16; 70.9%) and more general medical
      conditions, along with higher primary care utilization. Patients who screened
      positive for BD reported worse health-related quality of life as well as impaired
      functioning, compared to those who screened negative. LIMITATIONS: Co-morbid
      mental disorders were not assessed. The cross-sectional design prevents firm
      cause-effect inferences. CONCLUSIONS: The prevalence of a positive screening for
      BD is high, clinically significant and under-recognized in Brazilian PC settings.

PMID- 22959681
TI  - Antidepressant use and associations with psychosocial work characteristics. A
      comparative study of Swedish and Danish gainfully employed.
AB  - BACKGROUND: Although depression is common, prevalence estimates of antidepressant
      use among the workforce and undisputed evidence relating psychosocial work
      characteristics to depression is scarce. This study cross-sectionally assesses
      the prevalence of antidepressant use among employed in Sweden and Denmark and
      prospectively examines associations between work characteristics and
      antidepressant use. METHODS: Data on work demands, influence and learning
      possibilities was collected 2005-2006 from two representative samples of employed
      aged 20-59 years from Sweden (n=4351) and Denmark (n=8064) and linked to
      purchases of antidepressants through national prescription drug registries.
      Standardized 12-month prevalences were calculated. Cox regressions on work
      characteristics and incident use were performed separately and estimates pooled.
      RESULTS: Employed Swedish residents had higher standardized prevalence than
      Danish, 6.0% compared to 5.0%. Working fast and conflicting demands were
      associated with incident use when estimates were pooled, but adjustment for
      baseline health attenuated these estimates. Emotionally disturbing situations
      were related to any incident use, and more strongly to use >179 defined daily
      dosages/year, even after adjustment for various covariates. LIMITATIONS:
      Statistics based on national prescription drug registries are influenced by,
      e.g., treatment seeking behaviours and other reasons for prescription than
      depression. Selective drop-out may also affect prevalence estimates. CONCLUSIONS:
      The study indicates that use of antidepressants among the workforce is relatively
      high and that employed Swedish residents had higher prevalence of antidepressant
      use than Danish. Relationships between work characteristics and antidepressant
      use were, however, similar with emotional demands showing the strongest
      association, indicating that particular groups of employees may be at increased
      risk.

PMID- 22959682
TI  - Early functional impairment in bipolar youth: a nested population-based case
      control study.
AB  - OBJECTIVES: The objective of this report is to evaluate functioning in bipolar
      disorder in a population-based sample of young adults (18 to 24 years old). To
      this end, people with bipolar disorder were compared with matched participants
      with only depressive episodes and control subjects without a history of mood
      episodes. METHODS: Case-control study nested in a population-based sample.
      Caseness was confirmed with the Structured Clinical Interview for DSM-IV. The
      Functioning Assessment Short Test was used as a measure of general functioning. A
      multivariate model was elaborated to account for potential confounders. RESULTS:
      The sample consisted of 231 subjects. Both bipolar disorder (coef=0.60, SE=0.14,
      p<0.001) and major depression (coef=0.44, SE=0.14, p=0.001) were associated with
      functioning in the multivariate model. Current depressive symptoms appeared to
      influence functioning in those with major depression (Z=2.05, p=0.04), but not in
      those with bipolar disorder (Z=0.78, p=0.43). LIMITATION: Neuropsychological
      testing was not performed and we see it as an important limitation of this study.
      CONCLUSION: This population-based study further reinforces the notion that
      functional impairment is a fundamental characteristic of bipolar illness. It is
      present from early stages and is not completely explained by mood symptoms.

PMID- 22959683
TI  - Comparing HAMD(17) and HAMD subscales on their ability to differentiate active
      treatment from placebo in randomized controlled trials.
AB  - BACKGROUND: The 17-item Hamilton depression rating scale (HAMD(17)) is the
      standard efficacy outcome in antidepressant clinical trials. It is criticized for
      multidimensionality and poorly discriminating treatment from placebo. HAMD
      subscales may overcome these limitations and reduce the sample size of clinical
      trials. This study compared the discriminative performance of the HAMD(17) and
      three established HAMD subscales (Bech, Maier-Philipp, Gibbons) across a range of
      antidepressants with different mechanisms of action. METHODS: We analyzed data
      from 24 clinical trials including 3692 patients randomized to tricyclic or
      tetracyclic antidepressants (TCAs or TeCAs), selective serotonin reuptake
      inhibitors (SSRIs) or placebo. Data were analyzed using a mixed model for
      repeated measurements (MMRM). Standardized effect sizes for the HAMD(17) and
      subscales were derived for every time-point, and their effect on sample size was
      evaluated. RESULTS: For TCAs and TeCAs vs. placebo, the HAMD(17) consistently
      provided the highest standardized effects. The sample size to establish efficacy
      at week six was >25 percent smaller than for any of the subscales. However, for
      SSRIs vs. placebo, the HAMD(17) provided slightly smaller standardized effects
      and was the least efficient outcome. There were no relevant differences between
      the subscales. LIMITATIONS: Data were derived exclusively from mirtazapine
      trials. Conclusions are restricted to clinical trial settings. CONCLUSIONS:
      Comparative performance of the HAMD(17) and various subscales strongly depends on
      type of antidepressant. Results support using HAMD(17) as primary endpoint in
      clinical trials, but it will be beneficial to pro-actively include subscales as
      additional endpoints to successfully establish treatment effects of new
      antidepressants.

PMID- 22959684
TI  - Religious attendance and social adjustment as protective against depression: a 10
      year prospective study.
AB  - BACKGROUND: Previous research has identified elevated social adjustment and
      frequent religious attendance as protective against depression. The present study
      aims to examine the association of frequency of religious services attendance
      with subsequent depression, while accounting for the effects of social
      adjustment. METHOD: Participants were 173 adult offspring of depressed and
      nondepressed parents, followed longitudinally over 25 years. Diagnosis was
      assessed with the Schedule for Affective Disorders and Schizophrenia-Lifetime
      Version. The Social Adjustment Scale-Self Report (SAS-SR) was used to assess
      social adjustment and frequency of religious services attendance was self
      reported. In a logistic regression analysis, major depression at 20 years was
      used as the outcome measure and the frequency of religious services attendance
      and social adjustment variables at 10 years as predictors. RESULTS: Frequent
      religious services attendance was found to protect against subsequent depression
      at a trend level. High functioning social adjustment was found to protect against
      subsequent depression, especially within the immediate and extended family.
      Adults without a depressed parent who reported attending religious services
      atleast once a month had a lower likelihood of subsequent depression. Among
      adults with a depressed parent, those with high functioning social adjustment had
      a lower likelihood of subsequent depression. LIMITATIONS: Measurement of social
      adjustment was non-specific to religious services. CONCLUSIONS: Frequent
      religious attendance may protect against major depression, independent from the
      effects of social adjustment. This protective quality may be attenuated in adults
      with a depressed parent. High functioning social adjustment may be protective
      only among offspring of depressed parents.

PMID- 22959685
TI  - State-trait anxiety inventory (STAI) scores during pregnancy following
      intervention with complementary therapies.
AB  - OBJECTIVE: We review intervention trials that have used the State-Trait Anxiety
      inventory (STAI) as a measure of maternal anxiety in pregnancy in order to
      provide ranges in scores before and after participation in complementary therapy
      based interventions to highlight the expected ranges of scores in pregnancy and
      determine whether anxiety in pregnancy is amenable to change when measured by the
      STAI. METHODS: Combinations of the key words "STAI", "state anxiety",
      "pregnancy", "anxiety", "maternal", "stress", "outcome" and "intervention" were
      used to search publications between January 1970 and January 2011. Studies
      eligible for inclusion recruited low risk, adult women to a non-pharmacological
      intervention or a comparator group, and measured anxiety at baseline and post
      intervention. RESULTS: Ten studies were eligible. Scores were routinely high
      compared to expected ranges in non-pregnant populations. Studies examining the
      immediate effects of an intervention consistently reported significantly lowered
      STAI scores after a single session. Likewise, studies examining the effect of
      interventions consisting of multiple sessions over the course of pregnancy found
      that those in the intervention group were more likely to show an improvement in
      STAI scores. LIMITATIONS: Heterogeneity in type and duration of intervention
      prevent drawing conclusions on which were most effective in reducing anxiety.
      CONCLUSION: Scores on the STAI appear amenable to change during pregnancy, both
      after a single session and multiple sessions of interventions designed to reduce
      maternal anxiety. This review offers a guideline for the expected range of scores
      for future studies examining the efficacy of interventions in pregnancy when
      using the STAI.

PMID- 22959686
TI  - Adolescent substance use disorder during the early stages of bipolar disorder: a
      prospective high-risk study.
AB  - BACKGROUND: There is a paucity of longitudinal data characterizing the
      relationship between substance use disorder (SUD) and the early clinical course
      of bipolar disorder (BD). We studied this relationship in a prospectively
      assessed cohort of high-risk offspring. METHODS: Eligible families had one parent
      with confirmed BD based on SADS-L interviews and best estimate diagnostic
      procedure. Offspring completed KSADS-PL interviews at baseline and were
      reassessed prospectively. DSM-IV diagnoses were made on blind consensus review
      using all available information. This analysis included 211 offspring >=12 years,
      and used GEE and linear mixed models to determine clinical characteristics
      differentiating those with compared to those without SUD, and CPH models to
      assess the relationship between SUD and the early stages of BD. RESULTS: Lifetime
      SUD was diagnosed in 24% of offspring; cannabis use being most common. The peak
      hazard of SUD was between 14 and 20 years of age. Male sex (HR 3.285; p=.0007), a
      prior mood disorder (HR 2.437; p=.0091) and parental history of SUD (HR 2.999;
      p=.0027) contributed to the risk of SUD in the offspring, while SUD predicted an
      increased risk of psychosis (HR 3.225; p=.0074). The estimated hazard of a major
      mood disorder in those offspring with compared to those without a prior SUD was
      almost 3-fold (HR 2.990 (p<=0.01). LIMITATIONS: The novel clinical staging model
      requires independent replication. CONCLUSIONS: SUD is a common comorbidity
      arising during the early course of BD, even before the first activated episode.
      Further research is needed to understand causative factors and to develop
      effective early intervention and prevention strategies.

PMID- 22959687
TI  - The pattern of the collagen fiber bundles of the capsule of the glenohumeral
      joint.
AB  - The macroscopic anatomy and the architecture of the collagen fiber bundles were
      studied in the joint capsules of 43 cadaver shoulders. All the specimens were
      transilluminoted by polarized light after preparation by Spalteholz' technique.
      Areas of high-fiber density and complex structure were examined histologically.
      The macroscopically recognizable ligaments are composed of collagen fiber bundles
      in several layers of differing thickness and orientation. A simple pattern of
      radial and circular fibers is found only in the relatively thin posterior
      capsule. A complex pattern of cross-linking was visible in the superior capsule,
      and a system of fiber bundles spirally crossing each other was present in the
      anterior/inferior capsule. The examination under polarized light revealed a
      continuous transition between the ligamentous reinforcements at the anterior
      inferior capsule, which radiated obliquely from the glenoid rim and varied
      greatly in form and orientation. The complicated structure of the joint capsule
      would suggest that the capsular cylinder has to be regarded as a functional
      entity and that the current biomechanical concepts must be modified if we want to
      understand its stabilizing effect. The structural features of the superior
      capsule present new insight about the pathogenesis of rotator cuff tearing, which
      can develop as a result of shearing stress between the capsular and tendinous
      layers.

PMID- 22959688
TI  - Passive glenohumeral joint stabilization: A biomechanical study.
AB  - Passive glenohumeral joint stability was tested in 10 cadaveric shoulder
      specimens, before and after venting of the intraarticulor space. Force
      displacement diagrams were measured with anterior, posterior, and inferior
      excursion, in neutral position, in 90 degrees  of abduction, and in a combination
      of 90 degrees  of abduction and 90 degrees  of external rotation. Displacement at
      50 Ns before venting averaged 11.17 mm posteriorly (SD = 6.48 mm), 7.15 mm
      anteriorly (SD = 5.51 mm), and 3.41 mm inferiorly (SD = 3.37 mm). Venting of the
      joint increased displacement by 47% anteriorly, 49% posteriorly, and 61 %
      inferiorly. In addition, mathematic model calculation was used to estimate the
      destabilizing forces at the glenohumeral joint during physiologic arm motion.
      This force approximated 970 N, cldarly more than passive stabilizers alone seem
      to be able to provide. It is therefore assumed that, in addition to passive joint
      stability, active stabilization plays a major role at the glenohumeral joint.

PMID- 22959689
TI  - Stabilizing function of the long head of the biceps in the hanging arm position.
AB  - The contribution of the long head of the biceps (LHB) to shoulder stability was
      studied. Nine fresh-frozen cadaveric shoulders were tested in the hanging arm
      position. The muscle belly of the long head of the biceps was removed and
      replaced with a spring device to apply load to the long head of the biceps. An
      electromagnetic tracking device was used to record the positions of the humeral
      head (1) without load and with loads of 1.5 kg and 3 kg on the long head of the
      biceps, (2) with 1.5 kg of force to the proximal humerus in three different
      directions, and (3) in three different rotations of the arm. Displacement in the
      anterior and posterior directions was significantly decreased by long head of the
      biceps loading and was less significant in internal rotation. Inferior
      displacement in external rotation was significantly decreased by long head of the
      biceps loading. It is concluded that in the hanging arm position, the long head
      of the biceps could, if contracted, provide some stabilizing function to the
      humeral head in all directions, and more importantly, in anterior/posterior
      directions. Furthermore, the stabilizing function of the LHB is influenced by
      rotation of the arm.

PMID- 22959690
TI  - Elbow joint instability: A kinematic model.
AB  - The effect of simultaneous ulnar and radial collateral ligament division on the
      kinematics of the elbow joint is studied in a cadaveric model. Severance of the
      anterior part of the ulnar collateral ligament and the annular ligament led to
      significant elbow joint instability in valgus and varus stress and in forced
      external and internal rotation. The mean maximum laxity in valgus stress and
      forced external rotation were 5.7 degrees  and 13.2 degrees . The forearms of the
      elbow joint specimens were transfixed in maximum pronation. During valgus and
      varus stress the corresponding spontaneous ulnar rotation of the specimens was
      recorded. The reproducibility of the instability pattern suggests that this model
      is suitable for evaluating stabilizing procedures aimed at correction of elbow
      joint instability before these procedures are introduced into patient care.

PMID- 22959691
TI  - An anatomic study of the axis of elbow movement in the coronal plane: Relevance
      to component alignment in elbow arthroplasty.
AB  - We have performed an anatomic study on cadaveric material identifying a
      relationship between the posterior cortex of the distal humerus and the axis of
      movement of the elbow joint with reference to the coronal plane. This study was
      performed on 11 cadaveric upper limbs in which the axis of movement relative to
      the coronal plane was identified and confirmed with an external fixator. The
      relation between this plane and the tangential plane of the posterior cortex of
      the distal humerus was investigated. Observations made at points progressively
      proximal to the humeral epicondyles demonstrated that the tangential plane of the
      posterior humeral cortex became increasingly inclined medially until it became
      parallel to the coronal axis of movement of the elbow joint at a point 25 to 35
      mm proximal to the medial epicondyle of the humerus. The relevance of this
      observation to the orientation of the humeral component of a total elbow joint
      replacement arthroplasty is discussed.

PMID- 22959692
TI  - Calcific tendinitis and rotator cuff tearing: A clinical and radiographic study.
AB  - Calcific tendinitis and rotator cuff tearing are among the most common tearing
      abnormalities of the rotator cuff. They are considered to be two different
      disease entities, but the two conditions can coexist. This study identifies the
      clinical and radiologic features of calcifying tendinitis in Oriental people and
      defines its relationship to rotator cuff tearing. From October 1989 through
      August 1992, there were 82 patients with calcifying tendinitis suffering from
      persistent shoulder pain, who received arthrographic examination. Most of the
      calcific depositions were located in the supraspinatus (70.7%) and infraspinatus
      (26.8%) tendons, and most (73.2%) were found in the critical zone. Twenty-three
      (28%) had arthrogrophic evidence of rotator cuff tearing, and five were confirmed
      by surgery. Most of the patients (77.9%) in the nontear group had an ill-defined
      texture, whereas in the tear group almost one half had a well-defined texture
      (43.5% vs 56.5%). The texture, shape of the calcific deposits, and the integrity
      of the rotator cuff were significantly related to the size of the calcific
      deposit. The presence of a calcium deposit does not rule out the possibility of a
      coexisting rotator cuff tear. The sex and age distribution of calcifying
      tendinitis in Oriental people is differnt from information reported in the
      Western literature.

PMID- 22959693
TI  - Calcifying tendinitis of the infraspinatus tendon simulating a bone tumor.

PMID- 22959694
TI  - Developmental dislocation of the radial head.
AB  - An unusual case of developmental dislocation of the radial head is reported. A 6
      year-old boy was referred for evaluation of his elbow and was diagnosed as having
      an anterior dislocation of the right radial head. No dislocation was present on
      the left. Subsequently, the left radial head dislocated anteriorly without
      associated trauma 1 year after the initial examination. Intraoperative findings
      on the right revealed the dislocation occurred during pronation of the forearm
      when the radius abutted the interosseous border of the ulna. Ulnar osteomy and
      reinstruction of the annular fragment were performed but were, not effective in
      preventing redislocation.

PMID- 22959695
TI  - Stabilizers of the glenohumeral joint.

PMID- 22959696
TI  - Parents with bipolar disorder: are disease characteristics good predictors of
      psychopathology in offspring?
AB  - PURPOSE: To investigate rates of psychopathology in the offspring of subjects
      with bipolar disorder (BP-offspring) compared to the offspring of healthy
      subjects (HC-offspring) in a Spanish sample and to study possible predictors of
      psychopathology in BP-offspring. SUBJECTS: Fifty BP-offspring from 36 families
      and 25 HC-offspring from 25 families. METHODS: Psychopathology was compared in BP
      offspring and HC-offspring. Factors associated with DSM-IV axis I disorders in BP
      offspring were analyzed using logistic regression. RESULTS: Half of BP-offspring
      fulfilled the diagnostic criteria for at least one axis I disorder with attention
      deficit/hyperactivity disorder (30%), anxiety disorders (14%) and affective
      disorders (10%) as the most frequent. After controlling for having more than one
      sibling in the study, the odds ratio for BP-offspring presenting an axis I
      disorder was 15.02 when a biological parent had bipolar disorder with a lifetime
      history of psychotic symptoms and 3.34 when one parent had bipolar II disorder.
      Moreover, a higher Global Assessment of Functioning score in the biological co
      parent was associated with a significantly lower frequency of axis I disorders in
      BP-offspring. DISCUSSION AND CONCLUSIONS: Psychopathology in BP-offspring should
      be routinely assessed, with special emphasis on children from parents with
      specific disease characteristics (psychosis, BP II disorder) in order to
      establish an early diagnosis and appropriate interventions.

PMID- 22959697
TI  - NAPA 2.0: the next giant leap.

PMID- 22959698
TI  - Comparing new templates and atlas-based segmentations in the volumetric analysis
      of brain magnetic resonance images for diagnosing Alzheimer's disease.
AB  - BACKGROUND: The segmentation of brain structures on magnetic resonance imaging
      scans for calculating regional brain volumes, using automated anatomic labeling,
      requires the use of both brain atlases and templates (template sets). This study
      aims to improve the accuracy of volumetric analysis of hippocampus (HP) and
      amygdala (AMG) in the assessment of early Alzheimer's disease (AD) by developing
      template sets that correspond more closely to the brains of elderly individuals.
      METHODS: Total intracranial volume and HP and AMG volumes were calculated for
      elderly subjects with no cognitive impairment (n = 103), with amnestic mild
      cognitive impairment (n = 68), or with probable AD (n = 46) using the following:
      (1) a template set consisting of a standard atlas (atlas S), drawn on a young
      adult male brain, and the widely used Montreal Neurological Institute template
      (MNI template set); (2) a template set (template S set) in which the template is
      based on smoothing the image from which atlas S is derived; and (3) a new
      template set (template E set) in which the template is based on an atlas (atlas
      E) created from the brain of an elderly individual. RESULTS: Correspondence to HP
      and AMG volumes derived from manual segmentation was highest with automated
      segmentation by template E set, intermediate with template S set, and lowest with
      the MNI template set. The areas under the receiver operating curve for
      distinguishing elderly subjects with no cognitive impairment from elderly
      subjects with amnestic mild cognitive impairment or probable AD and the
      correlations between HP and AMG volumes and cognitive and functional scores were
      highest for template E set, intermediate for template S set, and lowest for the
      MNI template set. CONCLUSIONS: The accuracy of automated anatomic labeling and
      the diagnostic value of the derived volumes are improved with template sets based
      on brain atlases closely resembling the anatomy of the to-be-segmented brain
      magnetic resonance imaging scans.

PMID- 22959700
TI  - Isolated pyramidal tract impairment in the central nervous system of adult-onset
      Krabbe disease with novel mutations in the GALC gene.
AB  - This report describes a 60-year-old female patient with Krabbe disease who
      presented with slowly progressive gait disturbance due to mild spastic
      paraplegia. Brain magnetic resonance imaging showed high-intensity lesions along
      the upper parts of the bilateral pyramidal tracts in fluid-attenuated inversion
      recovery images. Central motor conduction time was prolonged both in the upper
      and the lower extremities, while central sensory conduction time was normal. The
      reduced lymphocyte galactocerebrosidase (GALC) activity and two novel mutations
      in the GALC gene, p.G496S and p.G569S, proved the diagnosis of Krabbe disease.
      Our findings show that adult-onset Krabbe disease is characterized by isolated
      pyramidal tract impairment in the central nervous system, both
      neurophysiologically and radiologically.

PMID- 22959699
TI  - Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations
      from the Ware Invitational Summit.
AB  - To address the pending public health crisis due to Alzheimer's disease (AD) and
      related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the
      University of Pennsylvania held a meeting entitled "State of the Science
      Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on
      June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers;
      Clinical Care and Health Services Research; Drug Development; and Health
      Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an
      integrated set of priorities, recommendations, and action plans, which are
      presented in this article.

PMID- 22959701
TI  - Endothelial progenitor cell response to antiproliferative drug exposure.
AB  - BACKGROUND: Vascular stent coverage by endothelial cells, derived from
      endothelial progenitor cells (EPC) is considered a surrogate for healing.
      However, the effects of antiproliferative drugs used in current drug-eluting
      stents (DES) on EPC proliferative and antithrombotic function remains poorly
      defined. METHOD AND RESULTS: Herein, we studied and compared the in vitro and in
      vivo effects of four antiproliferative drugs - paclitaxel, sirolimus, everolimus,
      and zotarolimus on several EPC properties including colony forming units (CFU),
      cell proliferation, apoptosis, antithrombotic and prothrombotic gene expression
      and nitric oxide (NO) as well as prostacyclin (PGI(2)) release. We also examined
      EPC migration and adhesion under flow conditions. We find that whereas all
      antiproliferative agents inhibited EPC proliferation and caused cell apoptosis,
      only paclitaxel and sirolimus reduced CFU formation. Paclitaxel treatment also
      resulted in the greatest down-regulation of antithrombotic gene expression and up
      regulation of prothrombotic gene expression. NO release, migration, and adhesion
      of EPC under shear stress were inhibited by all antiproliferative drugs, most
      notably by paclitaxel and sirolimus. CONCLUSIONS: These results indicate that
      antiproliferative drugs on DES, particularly paclitaxel, impair the proliferative
      and antithrombotic functions of EPC, and thereby could contribute to incomplete
      vascular healing and increase the risk of stent thrombosis.

PMID- 22959702
TI  - Impact of multiple antigenic epitopes from ApoB100, hHSP60 and Chlamydophila
      pneumoniae on atherosclerotic lesion development in Apob(tm2Sgy)Ldlr(tm1Her)J
      mice.
AB  - AIMS: To assess whether immunizing Apob(tm2Sgy)Ldlr(tm1Her)J mice simultaneously
      with different atherosclerosis-related epitopes engineered in a single
      recombinant protein is effective in reducing atherosclerotic lesions. METHODS AND
      RESULTS: Antigenic epitopes were incorporated into a dendroaspin scaffold: AHC
      (ApoB100 peptide + hHSP60 peptide [hHSP60(153-163)] + putative epitope derived
      from Chlamydophila pneumoniae [Cpn]) and AHHC (AHC + hHSP60(303-312)); and were
      compared with construct A (ApoB peptide), construct H (hHSP60(153-163)), and
      construct AH (ApoB100 peptide + hHSP60(153-163)). Immunization with 2 multiple
      antigenic epitope constructs elicited high levels of antibodies against each
      epitope in Apob(tm2Sgy)Ldlr(tm1Her)J mice (apart from hHSP60(153-163), which
      induced a low antibody response). Histological analyses demonstrated that the
      mice immunized with AHHC and AHC showed significant reductions in the size of
      atherosclerostic lesions compared with controls (63.8% and 63.2%; P < 0.001,
      respectively), and significantly greater reductions in lesions size compared with
      those after immunization with construct A (24.9%; P < 0.01), H (26.8%; P < 0.05),
      and AH (42.9%; P < 0.001). Moreover, combination of 2 short Cpn peptides along
      with ApoB and hHSP60 peptides had an additive effect on reducing the lesion
      without Cpn infection. Reduction in plaque size correlated with cellular
      infiltration and cytokine/chemokine secretion in serum or by stimulated spleen
      cells as well as specific cellular immune responses when compared with controls.
      CONCLUSIONS: Immunization of mice with a single construct containing multiple
      epitopes derived from ApoB100, hHSP60 and Cpn was more effective in reducing
      early atherosclerotic lesions through the induction of a specific Treg-cell
      response than was the construct containing either mono- or bi-epitopes. This
      approach offers attractive opportunities for the design of protein-based,
      multivalent vaccines against atherosclerosis.

PMID- 22959703
TI  - [Will multiple sclerosis (MS) susceptibility genes one day become biomarkers for
      MS diagnosis?].
AB  - Over the past 5 years, studies of multiple sclerosis (MS) genes have made
      spectacular progress. Today, more than 50 genes have been found to have an
      established role in MS, and there is no doubt that this list will continue to
      grow. The genes identified so far point to the metabolic pathways involving the
      immune system, thereby suggesting than inflammation is an early process in the
      course of the disease and probably the major cause of the axonal degeneration
      that results in neurological deficiencies and handicap. They also raise the
      question of the usefulness of these biomarkers in the diagnosis of MS.

PMID- 22959704
TI  - [Paraplegia following combined spinal-epidural anesthesia in a patient with an
      undiagnosed ependymoma].

PMID- 22959705
TI  - [Transcranial direct current stimulation: a new tool for neurostimulation].
AB  - Transcranial direct current stimulation (tDCS) is a safe method to modulate
      cortical excitability. Anodal stimulation can improve the stimulated area's
      functions whereas cathodal stimulation reduces them. Currently, a lot of clinical
      trials have been conducted to study the effect of tDCS on post-stroke motor and
      language deficits, in depression, chronic pain, memory impairment and tinnitus in
      order to decrease symptoms. Results showed that, if an effect is observed with
      tDCS, it does not persist over time. Current studies suggest that direct current
      stimulation is a promising technique that helps to improve rehabilitation after
      stroke, to enhance cognitive deficiencies, to reduce depression and to relieve
      chronic pain. Moreover, it is a safe, simple and cheap device that could be
      easily integrated in a rehabilitation program.

PMID- 22959706
TI  - EV-077 in vitro inhibits platelet aggregation in type-2 diabetics on aspirin.
AB  - INTRODUCTION: This study aimed to characterize the in vitro effect of EV-077, a
      compound that antagonises the binding of prostanoids and isoprostanes to the
      thromboxane receptor (TP) and inhibits the thromboxane synthase (TS), on platelet
      aggregation of patients with type-2 diabetes and coronary artery disease (CAD) on
      chronic aspirin treatment. The effect of EV-077 on 8-iso-PGE(2)-mediated TP
      receptor contraction of human arteries was also investigated. MATERIALS AND
      METHODS: Fifty-two type-2 diabetics with CAD on chronic aspirin (100 mg)
      treatment were studied. Arachidonic acid-induced platelet aggregation was
      measured by impedance aggregometry in platelet-rich plasma (PRP) and whole blood
      anticoagulated with hirudin, and by light transmission aggregometry in citrate
      anticoagulated PRP following 10-min in vitro exposure to EV-077 (100 nmol/l) or
      control. The effect of EV-077 was measured on isometric contraction of 24 human
      umbilical arteries induced by isoprostane 8-iso-PGE(2). RESULTS: Arachidonic acid
      (1 mmol/l) induced substantial aggregation in hirudin-anticoagulated whole blood
      (63 +/- 4 AU), which was significantly reduced by in vitro exposure to EV-077 (38
      +/- 3 AU, P<0.001). Virtually no arachidonic acid-induced aggregation in citrate
      anticoagulated or hirudin-anticoagulated PRP was observed. EV-077 potently,
      competitively and reversibly inhibited TP mediated contraction of umbilical
      arteries by 8-iso-PGE(2) (P<0.01). CONCLUSIONS: Aspirin did not completely
      inhibit arachidonic acid-induced platelet aggregation in whole blood from type-2
      diabetics with CAD. This aggregation is likely induced by prostanoids and/or
      isoprostanes produced by leukocytes, because it was significantly reduced by EV
      077. The TP receptor-mediated contraction of human arteries induced by
      isoprostane 8-iso-PGE(2) was effectively inhibited by EV-077.

PMID- 22959707
TI  - Tamoxifen-associated thromboembolism in breast cancer.

PMID- 22959708
TI  - Blood flow simulation and vascular reconstruction.
AB  - In medical practice, bypass grafts are commonly used as an alternative route
      around strongly stenosed or occluded arteries. In contrast to arterial
      bifurcations, surgically created anastomosis can be modified with the objective
      of enabling optimal graft geometry to yield a flow environment that improves its
      longevity. This paper presents a three dimensional numerical study of blood flow
      through bypass systems with different geometries. Coupled with the finite element
      solver a shape optimization framework considering a genetic algorithm is
      presented. Numerical results show the benefits of understanding blood flow
      hemodynamic at anastomosis junctions achieving design improvements. Minimizing
      recirculation zones and flow stagnation can be useful in surgical planning.

PMID- 22959709
TI  - Increased metabotropic glutamate receptor subtype 5 availability in human brain
      after one night without sleep.
AB  - BACKGROUND: Sleep deprivation (wake therapy) provides rapid clinical relief in
      many patients with major depressive disorder (MDD). Changes in glutamatergic
      neurotransmission may contribute to the antidepressant response, yet the exact
      underlying mechanisms are unknown. Metabotropic glutamate receptors of subtype 5
      (mGluR5) are importantly involved in modulating glutamatergic neurotransmission
      and neuronal plasticity. The density of these receptors is reduced in the brain
      of patients with MDD, particularly in brain structures involved in regulating
      wakefulness and sleep. We hypothesized that prolonged wakefulness would increase
      mGluR5 availability in human brain. METHODS: Metabotropic glutamate receptor
      subtype 5 binding was quantified with positron emission tomography in 22 young
      healthy men who completed two experimental blocks separated by 1 week. Two
      positron emission tomography examinations were conducted in randomized, crossover
      fashion with the highly selective radioligand, 11C-ABP688, once after 9 hours
      (sleep control) and once after 33 hours (sleep deprivation) of controlled
      wakefulness. 11C-ABP688 uptake was quantified in 13 volumes of interest with high
      mGluR5 expression and presumed involvement in sleep-wake regulation. RESULTS:
      Sleep deprivation induced a global increase in mGluR5 binding when compared with
      sleep control (p<.006). In anterior cingulate cortex, insula, medial temporal
      lobe, parahippocampal gyrus, striatum, and amygdala, this increase correlated
      significantly with the sleep deprivation-induced increase in subjective
      sleepiness. CONCLUSIONS: This molecular imaging study demonstrates that cerebral
      functional mGluR5 availability is increased after a single night without sleep.
      Given that mGluR5 density is reduced in MDD, further research is warranted to
      examine whether this mechanism is involved in the potent antidepressant effect of
      wake therapy.

PMID- 22959710
TI  - Effects of thyroxin therapy on different analytes related to obesity and
      inflammation in dogs with hypothyroidism.
AB  - Hypothyroidism in dogs is accompanied by changes in intermediary metabolism
      including alterations in bodyweight (BW), insulin resistance, and lipid profile.
      In this study, changes in selected adipokines (adiponectin, leptin),
      butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive
      protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with
      hypothyroidism under thyroxin therapy. Blood samples were collected when
      hypothyroidism was diagnosed (before treatment) and after treatment with
      thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group
      A), whereas the remainder were considered to have been insufficiently treated
      (group B). Following treatment, group A dogs demonstrated a statistically
      significant decrease in canine thyroid stimulating hormone (c-TSH) (P<0.001) and
      an increase in free thyroxine (fT4) (P<0.001) concentrations, associated with a
      significant decrease in BW (P<0.05), leptin (P<0.01), and adiponectin, (P<0.001)
      and an increase in BChE (P<0.01) and Hp (P<0.05). Group B dogs showed no
      statistically significant changes in c-TSH, but had a significant increase in fT4
      (P<0.001) accompanied by a significant decrease in adiponectin (P<0.05) of lower
      magnitude than group A. No significant changes in the mean circulating levels of
      APPs were observed in both groups, with the exception of an increase in Hp
      (P<0.05) in group A. In summary, the successful treatment of hypothyroidism
      reduces circulating levels of adiponectin and leptin, while increasing BChE
      activity in dogs. The mean increase in Hp values and decrease in SAA for some of
      the dogs after treatment warrants further investigation.

PMID- 22959711
TI  - Role of conformational sampling of Ser16 and Thr17-phosphorylated phospholamban
      in interactions with SERCA.
AB  - Phosphorylation of phospholamban (PLB) at Ser16 and/ or Thr17 is believed to
      release its inhibitory effect on sarcoplasmic reticulum calcium ATPase. Ser16
      phosphorylation of PLB has been suggested to cause a conformational change that
      alters the interaction between the enzyme and protein. Using computer
      simulations, the conformational sampling of Ser16 phosphorylated PLB in implicit
      membrane environment is compared here with the unphosphorylated PLB system to
      investigate these conformational changes. The results suggest that conformational
      changes in the cytoplasmic domain of PLB upon phosphorylation at Ser16 increase
      the likelihood of unfavorable interactions with SERCA in the E2 state prompting a
      conformational switch of SERCA from E2 to E1. Phosphorylation of PLB at Thr17 on
      the other hand does not appear to affect interactions with SERCA significantly
      suggesting that the mechanism of releasing the inhibitory effect is different
      between Thr17 phosphorylated and Ser16 phosphorylated PLB.

PMID- 22959712
TI  - Function of plastochromanol and other biological prenyllipids in the inhibition
      of lipid peroxidation-A comparative study in model systems.
AB  - Lipid peroxidation is an oxidation reaction leading to the generation of lipid
      hydroperoxides. Here we present comparative data on the inhibition of lipid
      peroxidation by a variety of biological prenyllipids in liposomes prepared from
      natural lipid membranes. Lipid peroxidation was initiated by hydrophilic and
      hydrophobic azo initiators, as well as by singlet oxygen generated via
      photosensitized reaction of hydrophobic zinc tetraphenylporphine. When lipid
      peroxidation was initiated in the water phase, tocopherols and plastochromanol-8
      were more effective than prenylquinols, such as plastoquinol-9, ubiquinol-10 or
      alpha-tocopherolquinol. However, if the peroxidation was initiated within the
      hydrophobic interior of liposome membranes, long-chain prenyllipids, such as
      plastoquinol-9 and plastochromanol-8, were considerably more active than
      tocopherols in the inhibition of the reaction. In the latter system, tocopherols
      showed even prooxidant activity. The prooxidant activity of alpha-tocopherol was
      prevented by plastoquinol, suggesting the reduction of alpha-tocopheroxyl radical
      by the quinol. All the investigated prenyllipids were able to inhibit singlet
      oxygen-mediated lipid peroxidation but the most active were prenylquinols in this
      respect. Among all the prenyllipids investigated, plastochromanol-8 was the most
      versatile antioxidant in the inhibition of lipid peroxidation initiated by the
      three different methods.

PMID- 22959713
TI  - Comparative effectiveness research in kidney disease: a national priority.

PMID- 22959714
TI  - Comparison of outcomes in patients with versus without diabetes mellitus after
      revascularization with everolimus- and sirolimus-eluting stents (from the SORT
      OUT IV trial).
AB  - Diabetes is associated with increased risk of major adverse cardiac events
      (MACEs) after percutaneous coronary intervention. The purpose of this substudy of
      the SORT OUT IV trial was to compare clinical outcomes in patients with and
      without diabetes mellitus treated with everolimus-eluting stents (EESs) or
      sirolimus-eluting stents (SESs). In total 2,774 patients (390 with diabetes,
      14.1%) were randomized to stent implantation with EESs (n = 1,390, diabetes in
      14.0%) or SESs (n = 1,384, diabetes in 14.2%). Randomization was stratified by
      presence/absence of diabetes. The primary end point was MACEs, a composite of
      cardiac death, myocardial infarction, definite stent thrombosis, or target vessel
      revascularization within 18 months. MACEs were higher in diabetic than in
      nondiabetic patients (13.1% vs 6.4%, hazard ratio [HR] 2.08, 95% confidence
      interval [CI] 1.51 to 2.86). In diabetic patients, MACEs were seen in 10.3% of
      those treated with EESs and in 15.8% of those treated with SESs (HR 0.63, 95% CI
      0.36 to 1.11). In nondiabetic patients, MACEs occurred in 6.6% of EES-treated and
      in 6.3% SES-treated patients (HR 1.06, 95% CI 0.77 to 1.46). In diabetics,
      cardiac death occurred in 3.1% of EES-treated and in 4.6% of SES-treated patients
      (HR 0.67, 95% CI 0.24 to 1.89), myocardial infarction occurred in 0.5% of EES
      treated and in 3.6% of SES-treated patients (HR 0.14, 95% CI 0.02 to 1.16), and
      clinically driven target lesion revascularization was needed in 3.1% of EES
      treated and in 7.7% of SES-treated patients (HR 0.40, 95% CI 0.15 to 1.02). No
      interaction between diabetes status and type of drug-eluting stent was found for
      the end points. In conclusion, patients with diabetes have higher MACE rates than
      nondiabetics. No significant differences in safety or efficacy outcomes after EES
      or SES implantation were present in nondiabetic or diabetic patients.

PMID- 22959715
TI  - Quality of life, anxiety and depression in adult patients after add-on of
      levetiracetam and conversion to levetiracetam monotherapy.
AB  - The aim of this study was to investigate the change of health related quality of
      life (HRQoL), anxiety and depression in adult patients in whom an adjunctive
      treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A
      prospective, open, investigator initiated multicenter study enrolled 140 patients
      in whom LEV was added to the existing antiepileptic medication. A total of 65
      patients who benefited from the 16-week add-on treatment with LEV (>=50% seizure
      reduction) were converted to LEV monotherapy (16-week follow-up). In LEV
      responders, HRQoL, anxiety and depression improved after add-on of LEV. The
      subsequent conversion to LEV monotherapy did not lead to a significant change in
      HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy,
      the improvements remained significant for most dimensions of HRQoL and for
      anxiety and depression. Patients' ratings of efficacy of LEV were related with
      their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved
      HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy
      did not inevitably improve HRQoL in LEV responders, but the positive effect was
      maintained in the majority of the patients. The effects were highly related to
      seizure reduction.

PMID- 22959716
TI  - Epileptic Amnesic Syndrome revealing Alzheimer's disease.
AB  - OBJECTIVE: To describe the aetiology of a particular form of late-onset temporal
      lobe epilepsy (TLE) - the Epileptic Amnesic Syndrome (EAS) - that can be
      responsible for cognitive decline. The syndrome is considered as a reversible
      cause of memory disturbances, but some patients remain unrelieved despite
      anticonvulsants. DESIGN: 4 case-reports and a brief discussion. SETTING:
      University Hospital. PATIENTS: 4 patients fulfilling the diagnosis criteria of
      EAS but for whom a progressive causative disease was suspected because they still
      complained from their memory after antiepileptic treatment. RESULTS: All patients
      had characteristics suggesting Alzheimer's disease. Memory disturbances were
      systematically combined with other non-episodic cognitive impairments. CSF
      biomarkers were compatible with AD pathological changes. Moreover, brain MRI
      showed temporal lobe atrophy and neurological examination showed subtle
      abnormalities in all 4. CONCLUSION: AD should be kept in mind even though the
      patients meet the clinical criteria of EAS. This short series highlights the
      clinical characteristics that should be considered as "red-flags" in EAS patients
      because their presence makes the diagnosis of EAS improbable. In such a
      situation, particularly when cognitive improvement is lacking under treatment, a
      lumbar puncture is warranted.

PMID- 22959717
TI  - Interplanetary space flight compared with fetal/neonatal motor strategy:
      Theoretical and practical implications.
AB  - The condition of simulated or real manned spaceflight, i.e. thermally comfortable
      microgravitation (G~0), is very similar to the intrauterine immersion to the
      amniotic fluid. Domination of fast muscle fibers and phasic movements forms the
      fetal strategy to survive in heating, strongly hypoxic, albeit normal for fetus,
      immersion. In adults, the adaptive response separately to microgravitation, heat
      stress and hypoxia also shifts muscle fiber properties to faster values. That
      allows to speculate about specific motor strategy induced by micro-or
      hypogravitation (fetal/microgravitation, or FM-strategy). After birth the newborn
      is subjected to a combined 'sensory attack' of Earth gravitation, cooler ambient
      temperature and normoxia which is actually hyperoxic for fetus. The process of
      parturition can be considered as equivalent to cosmonaut's/astronaut's transition
      from microgravitation back to Earth gravitation (G=1) during landing. These
      factors also act simultaneously and constitute another set of sensory inputs with
      the effect that is opposite to the intrauterine condition. In normal gravitation,
      comfortable temperature and normoxia decreases the motor unit activity (MU)
      firing rate to a level, characteristic for the regular Earth condition. In
      contrast to 'faster' fetal adaptive motor response (microgravitation, heat,
      hypoxia), the post-natal adult set of conditions (lower, but still normal
      temperature, normoxia, 1G gravitation, healthy maturation) may represent the
      'Earth' adaptive motor response, or the (gravitation/Earth, or GE-strategy). The
      motor system undergoes a second profound remodeling in older people during
      healthy ageing that results in further domination of slow muscle fibers and
      slowing down motor unit activity, simulating the condition of hypergravitation
      (G>1). Similar slowing adaptive responses are represented by cold and hyperoxia
      thus forming further motor strategy that could be named as SJ-strategy (after
      'slow' and Jupiter - the most massive planet and the only planet with G>1 in the
      solar system). These strategies suppose that definite sensory inputs and
      conditions may substitute each other due to its equivalent action on the motor
      system. Thus, cold 'sensory attack' may serve as a 'surrogate' for gravitation
      because these two conditions exert equivalent stimulating action on muscle tone.
      In that respect long-term mild cooling exposures or shorter severe cold exposures
      may be considered as a prophylactic countermeasure against hazardous action of
      weightlessness. Also, combination of cooling sensory intervention with
      traditional and well- documented interventions (whole body vibration and
      stimulation of 'support zone' afferents) may elevate their anti-microgravitation
      efficiency.

PMID- 22959718
TI  - Validation of an egg-injection method for embryotoxicity studies in a small,
      model songbird, the zebra finch (Taeniopygia guttata).
AB  - Female birds deposit or 'excrete' lipophilic contaminants to their eggs during
      egg formation. Concentrations of xenobiotics in bird eggs can therefore
      accurately indicate levels of contamination in the environment and sampling of
      bird eggs is commonly used as a bio-monitoring tool. It is widely assumed that
      maternally transferred contaminants cause adverse effects on embryos but there
      has been relatively little experimental work confirming direct developmental
      effects (cf. behaviorally-mediated effects). We validated the use of egg
      injection for studies of in ovo exposure to xenobiotics for a small songbird
      model species, the zebra finch (Taeniopygia guttata), where egg weight averages
      only 1 g. We investigated a) the effect of puncturing eggs with or without
      vehicle (DMSO) injection on egg fate (embryo development), chick hatching success
      and subsequent growth to 90 days (sexual maturity), and b) effects of two vehicle
      solutions (DMSO and safflower oil) on embryo and chick growth. PBDE-99 and -47
      were measured in in ovo PBDE-treated eggs, chicks and adults to investigate
      relationships between putative injection amounts and the time course of
      metabolism (debromination) of PBDE-99 during early development. We successfully
      injected a small volume (5 MUL) of vehicle into eggs, at incubation day 0, with
      no effects on egg or embryo fate and with hatchability similar to that for non
      manipulated eggs in our captive-breeding colony (43% vs. 48%). We did find some
      evidence for an inhibitory effect of DMSO vehicle on post-hatching chick growth,
      in male chicks only. This method can be used to treat eggs in a dose-dependent,
      and ecologically-relevant, manner with PBDE-99, based on chemical analysis of
      eggs, hatchling and adults.

PMID- 22959719
TI  - Photocatalytic degradation kinetics and mechanism of phenobarbital in TiO(2)
      aqueous solution.
AB  - 5-Ethyl-5-phenylpyrimidine-2,4,6(1H, 3H, 5H)-trione is an anti-convulsant used to
      treat disorders of movement, e.g. tremors. This work deals with the
      transformation of phenobarbital by UV/TiO(2) heterogeneous photocatalysis, to
      assess the decomposition of the pharmaceutical compound, to identify
      intermediates, as well as to elucidate some mechanistic details of the
      degradation. The photocatalytic removal efficiency of 100 MUm phenobarbital is
      about 80% within 60 min, while the degradation efficiency of phenobarbital was
      better in alkaline solution. The study on contribution of reactive oxidative
      species (ROSs) has shown that ()OH is responsible for the major degradation of
      phenobarbital, while the photohole, photoelectrons and the other ROSs have the
      minor contribution to the degradation. Finally, based on the identification of
      degradation intermediates, two main photocatalytic degradation pathways have been
      tentatively proposed, including the hydroxylation and cleavage of pyrimidine ring
      in the phenobarbital molecule respectively. Certainly, the phenobarbital can be
      mineralized when the photocatalytic reaction time prolongs.

PMID- 22959720
TI  - Phenoxyalkanoic acid herbicide sorption and the effect of co-application in a
      Haplic Cambisol with contrasting management.
AB  - The adsorption and desorption behaviour of two phenoxyalkanoic acid herbicides
      (MCPA and mecoprop-p) in a Haplic Cambisol with tillage and grassland management
      was examined using a batch equilibrium method. Additionally, the effect on
      adsorption of the simultaneous presence of the two herbicides was also studied.
      The sorption equilibrium was reached within 24h for adsorption and desorption in
      both soils. The experimental sorption data for MCPA and mecoprop-p fitted the
      Freundlich and the linear adsorption isotherms very well (R(2)>0.99). The
      Freundlich exponent values of the adsorption isotherm ranged from 0.91 to 0.98
      indicating a non-linear and a linear adsorption of the two chemicals studied.
      Generally, mecoprop-p showed lower adsorption than MCPA, although the adsorption
      of both phenoxyalkanoic acid herbicides was low. The adsorption process was not
      fully reversed during one washing cycle, as the K(f) values for desorption were
      greater than corresponding K(f) values for adsorption. The Freundlich exponent
      (1/n) of the MCPA adsorption isotherm was affected by the simultaneous presence
      of both herbicides and tended more towards non-linearity, whilst the mecoprop-p
      adsorption exponent remained unaltered. The Freundlich and the linear adsorption
      coefficients calculated in the mix study were not that different from the
      adsorption coefficients calculated in the single compound study, and therefore
      single compound adsorption data can be used when modelling the fate of
      simultaneously applied phenoxyalkanoic acid herbicides. The study also indicated
      that both herbicides were poorly sorbed by the soils studied, and therefore may
      pose a risk of surface and/or groundwater pollution in Ireland.

PMID- 22959721
TI  - Lipid monolayer collapse and microbubble stability.
AB  - Microbubbles are micrometer-size gaseous particles suspended in water, and they
      are often stabilized by a lipid monolayer shell. Natural microbubbles are found
      in freshwater and saltwater systems, and engineered microbubbles have a variety
      of applications in food sciences, biotechnology and medicine. Lipid-coated
      microbubbles are found to have remarkable stability and mechanical behavior owing
      to the resistance of the lipid monolayer encapsulation to collapse. The purpose
      of this review is to tie in recent observations of lipid-coated microbubble
      dissolution and gas exchange with current literature on the physics of lipid
      monolayer collapse in the context of lung surfactant. Based on this analysis, we
      conclude that microbubble shells collapse through the nucleation of microscopic
      folds, which then catalyze the formation and aggregation of new folds, leading to
      macroscopic folding events. This process results in a cyclic behavior of crumple
      to-smooth transitions, which can be modulated through lipid composition.
      Eventually, the microbubbles stabilize at 1-2 MUm diameter, regardless of initial
      size or lipid composition, and various mechanisms for this stabilization are
      postulated. Our ultimate goal is to inspire the reader to consider lipid
      monolayer collapse as the main long-term stabilizing mechanism for lipid-coated
      microbubbles, and to stimulate the use of microbubbles as a platform for studying
      monolayer collapse phenomena.

PMID- 22959722
TI  - MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple.
AB  - Macrophage migration inhibitory factor (MIF) is increased in kidney and urine
      during kidney disease. MIF binds to and activates CD74 and chemokine receptors
      CXCR2 and CXCR4. CD74 is a protein trafficking regulator and a cell membrane
      receptor for MIF, D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins.
      MIF signaling through CD74 requires CD44. CD74, CD44 and CXCR4 are upregulated in
      renal cells in diseased kidneys and MIF activation of CD74 in kidney cells
      promotes an inflammatory response. MIF or CXCR2 targeting protects from
      experimental kidney injury, CD44 deficiency modulates kidney injury and CXCR4
      activation promotes glomerular injury. However, the contribution of MIF or MIF-2
      to these actions of MIF receptors has not been explored. The safety and efficacy
      of strategies targeting MIF, CD74, CD44 and CXCR4 are under study in humans.

PMID- 22959727
TI  - A touch screen-automated cognitive test battery reveals impaired attention,
      memory abnormalities, and increased response inhibition in the TgCRND8 mouse
      model of Alzheimer's disease.
AB  - Transgenic mouse models of Alzheimer's disease (AD) with abundant beta-amyloid
      develop memory impairments. However, multiple nonmnemonic cognitive domains such
      as attention and executive control are also compromised early in AD individuals,
      but have not been routinely assessed in animal models. Here, we assessed the
      cognitive abilities of TgCRND8 mice-a widely used model of beta-amyloid pathology
      with a touch screen-based automated test battery. The test battery comprises
      highly translatable tests of multiple cognitive constructs impaired in human AD,
      such as memory, attention, and response control, as well as appropriate control
      tasks. We found that familial AD mutations affect not only memory, but also cause
      significant alterations of sustained attention and behavioral flexibility.
      Because changes in attention and response inhibition may affect performance on
      tests of other cognitive abilities including memory, our findings have important
      consequences for the assessment of disease mechanisms and therapeutics in animal
      models of AD. A more comprehensive phenotyping with specialized, multicomponent
      cognitive test batteries for mice might significantly advance translation from
      preclinical mouse studies to the clinic.

PMID- 22959729
TI  - A research group from the European General Practice Research Network (EGPRN)
      explores the concept of multimorbidity for further research into long term care.

PMID- 22959730
TI  - Falls and nursing home residents with cognitive impairment: new insights into
      quality measures and interventions.
AB  - OBJECTIVES: Prevention and public reporting of falls have suffered due to
      inadequate attention given to the association of falls and cognitive impairment
      (CI) among nursing home (NH) residents. This study examines the relationship
      between CI, residence on dementia special care units (SCUs) and other resident
      characteristics and likelihood of residents experiencing new falls in NHs.
      DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 21,587
      residents from 381 Minnesota NHs. MEASUREMENTS: The NH Minimum Data Set (MDS) for
      21,587 residents from 381 Minnesota NHs in the first calendar quarter of 2008
      were analyzed. New falls, (fall noted on a current MDS assessment but not on a
      prior assessment); cognitive status, (as defined by Cognitive Performance Scale);
      residence on an SCU, and health and functional status covariates were recorded. A
      random effects logistic regression model was used to examine relationships
      between new falls and the resident's cognitive status, type of unit, and
      covariates. RESULTS: The likelihood of a new fall had a nonlinear association
      with CI. Compared with residents with normal or mild CI, the likelihood of a new
      fall was significantly higher among residents with moderate CI (OR= 1.43). The
      risk decreased slightly (OR= 1.34) for residents with more advanced CI, whereas
      the presence of severe CI was not significantly associated with new falls.
      Overall the likelihood of new falls was significantly higher for residents on
      SCUs compared with those on conventional units (OR= 1.27). CONCLUSIONS: Severity
      of CI and residence on SCU impact fall incidence and should be accounted for in
      future fall- prevention interventions and quality-reporting indicators and
      measures.

PMID- 22959731
TI  - Updated 2012 Beers Criteria: what's noteworthy and cautionary?

PMID- 22959728
TI  - Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
AB  - Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset
      neurodegenerative disease. Individuals with ALS rapidly progress to paralysis and
      die from respiratory failure within 3 to 5 years after symptom onset.
      Epidemiological factors explain only a modest amount of the risk for ALS.
      However, there is growing evidence of a strong genetic component to both familial
      and sporadic ALS risk. The International Consortium on Amyotrophic Lateral
      Sclerosis Genetics was established to bring together existing genome-wide
      association cohorts and identify sporadic ALS susceptibility and age at symptom
      onset loci. Here, we report the results of a meta-analysis of the International
      Consortium on Amyotrophic Lateral Sclerosis Genetics genome-wide association
      samples, consisting of 4243 ALS cases and 5112 controls from 13 European ancestry
      cohorts from across the United States and Europe. Eight genomic regions provided
      evidence of association with ALS, including 9p21.2 (rs3849942, odds ratio [OR] =
      1.21; p = 4.41 * 10(-7)), 17p11.2 (rs7477, OR = 1.30; p = 2.89 * 10(-7)), and
      19p13 (rs12608932, OR = 1.37, p = 1.29 * 10(-7)). Six genomic regions were
      associated with age at onset of ALS. The strongest evidence for an age of onset
      locus was observed at 1p34.1, with comparable evidence at rs3011225
      (R(2)(partial) = 0.0061; p = 6.59 * 10(-8)) and rs803675 (R(2)(partial) = 0.0060;
      p = 6.96 * 10(-8)). These associations were consistent across all 13 cohorts. For
      rs3011225, individuals with at least 1 copy of the minor allele had an earlier
      average age of onset of over 2 years. Identifying the underlying pathways
      influencing susceptibility to and age at onset of ALS may provide insight into
      the pathogenic mechanisms and motivate new pharmacologic targets for this fatal
      neurodegenerative disease.

PMID- 22959732
TI  - Racial disparities in end-of-life planning and services for deceased nursing home
      residents.
AB  - OBJECTIVE: This study examined the relationship between race and advance
      directives, hospice services, and hospitalization at the end of life among
      deceased nursing home residents. DESIGN: Secondary data analysis using the 2007
      Minimum Data Set (MDS) was used to identify nursing home residents who died
      during the year, as well as to explore relationships between race and the study
      variables of interest. SETTING: US nursing homes certified for Medicare or
      Medicaid reimbursement were included in the study. PARTICIPANTS: Nursing home
      residents 65 years of age and older who had a completed MDS full assessment and
      one quarterly assessment, and died while residing in the facility during 2007.
      MEASUREMENTS: MDS documentation of advance directive measures, hospice use, and
      hospitalizations were assessed for white, black, Hispanic, and Asian residents
      with linear regression models fitted to each dependent variable (outcome) with
      "race" as the main predictor. RESULTS: Across different types of advance
      directives, black, Hispanic, and Asian nursing home residents were significantly
      less likely to have these documented in their files. Compared with white
      residents, Asian residents were also significantly less likely to receive hospice
      services during their last year of life, whereas Hispanic residents were more
      likely to receive services. Finally, all racial groups were more likely to
      experience hospitalization within 90 days before death, regardless of whether
      they had documentation of a do not hospitalize order. CONCLUSION: As the racial
      profile of nursing home residents becomes more diverse, recognizing differences
      in end-of-life planning and treatment preferences, as well as the implementation
      of tailored programs for specific groups, will continue to increase in
      importance.

PMID- 22959734
TI  - Envisioning quality psychosocial care in nursing homes: the role of social work.
AB  - This article articulates a vision of excellent psychosocial care in nursing homes
      using a quality assurance perspective and illustrates how skills of professional
      social workers can contribute to enhanced psychosocial care in this setting.
      Building on knowledge of actual and best practice roles for social work in
      nursing homes, this article serves as a call to differentiate professional social
      work from paraprofessional social services to support quality improvements for
      interprofessional psychosocial care and improved quality of life outcomes for
      residents.

PMID- 22959733
TI  - Reducing cost by reducing polypharmacy: the polypharmacy outcomes project.
AB  - OBJECTIVE: To examine the effect of intervention by geriatric medicine fellows
      and a geriatrician on medication cost among long term care residents with
      polypharmacy. DESIGN: Interventional study. SETTING: A single hospital-affiliated
      long term care facility. PARTICIPANTS: Long term care residents with
      polypharmacy, defined as being on 9 or more medications. INTERVENTION: Medication
      lists of all nursing home residents were reviewed in October 2007 by geriatric
      medicine fellows and a faculty geriatrician using the 2003 Beers Criteria and the
      Epocrates online drug-drug interaction program. Recommendations for each resident
      were prepared and discussed directly with their primary physicians, who made the
      final decisions regarding medication discontinuation or taper. MEASUREMENTS: Mean
      monthly costs (derived from current retail prices) for overall as well as
      scheduled and pro re nata (PRN) medications were compared before and after the
      intervention. Estimated reduction in nursing administration time and cost were
      calculated based on published literature on medication administration time and
      nursing labor costs. RESULTS: Seventy-four (46.3%) of 160 residents were on 9 or
      more medications. Four residents died or were discharged before the intervention,
      leaving a final sample of 70 residents for the intervention. After the
      intervention, mean monthly medication costs per resident significantly decreased;
      overall medications, from $874.27 to $843.56 (P < .0001); scheduled medications,
      from $814.05 to $801.14 (P= .007); PRN medications, from $60.22 to $42.43 (P <
      .0001). Gastrointestinal medications demonstrated the highest cost savings of all
      medication categories (eg, promethazine and proton pump inhibitors), followed by
      central nervous system-active medications (including benzodiazepines and
      fluoxetine), then analgesics and diabetes medications. CONCLUSION: This
      polypharmacy reduction intervention by physicians used readily available tools,
      demonstrated a significant decrease in medication-related costs, and provided
      training in the core competencies of practice-based learning and improvement and
      systems-based practice to geriatric medicine fellows in long term care.

PMID- 22959735
TI  - Sarcopenia: a novel clinical condition or still a matter for research?

PMID- 22959737
TI  - Patterns of injury and otolaryngology intervention in pediatric neck trauma.
AB  - BACKGROUND: Neck trauma in the pediatric population is relatively rare with
      limited discussion in the literature describing the injury patterns and outcomes
      of all neck trauma victims. This study characterizes pediatric neck trauma both
      inside and outside the context of injuries requiring otolaryngology (ENT)
      intervention. METHODS: Patients sustaining neck trauma presenting to a single
      tertiary care hospital between January 2001 and June 2010 were included.
      Demographic information was obtained in addition to information regarding the
      initial hospital stay and follow up visits related to the initial trauma.
      RESULTS: Seventy-four patients were included. Blunt injuries were found in 44
      children with 30 sustaining penetrating injuries. Twenty-eight percent of
      patients had an ENT consultation. Those patients with injuries warranting ENT
      consultation were nearly 3 times more likely to require intubation than those
      without an ENT consultation (p=0.009). Laryngotracheal injuries were documented
      in 11 patients with 6 of these characterized as major injuries and 5 minor
      injuries. CONCLUSION: Pediatric neck trauma represents a spectrum of injuries
      from ecchymosis to major laryngotracheal injury. Otolaryngology involvement is
      not necessary in all cases; however, one must be aware of the risk of
      laryngotracheal injury, particularly with blunt trauma and there should be a low
      threshold for Otolaryngology consultation and endoscopy.

PMID- 22959738
TI  - Lower island trapezius myocutaneous flap reconstruction of a large neck defect in
      an infant.
AB  - Free tissues transfer has been well-described in infants but there is limited
      data on techniques for reconstruction of large neck defects with regional
      myocutaneous flaps in this population. We report on the use of a lower island
      trapezius myocutaneous flap to reconstruct a large posterior neck and occiput
      wound in an 18-month-old child. The use of a regional myocutaneous flap allowed
      for reliable transfer of a relatively large volume of skin and soft tissue,
      providing coverage of the internal jugular vein and spinal accessory nerve as
      well as limiting the likelihood of debilitating scar contracture.

PMID- 22959736
TI  - The great unravelling: chromatin as a modulator of the aging process.
AB  - During embryogenesis, the establishment of chromatin states permits the
      implementation of genetic programs that allow the faithful development of the
      organism. However, these states are not fixed and there is much evidence that
      stochastic or chronic deterioration of chromatin organization, as correlated by
      transcriptional alterations and the accumulation of DNA damage in cells, occurs
      during the lifespan of the individual. Whether causal or simply a byproduct of
      macromolecular decay, these changes in chromatin states have emerged as
      potentially central conduits of mammalian aging. This review explores the current
      state of our understanding of the links between chromatin organization and aging.

PMID- 22959740
TI  - Multi-objective control of nonlinear boiler-turbine dynamics with actuator
      magnitude and rate constraints.
AB  - This paper investigates multi-objective controller design approaches for
      nonlinear boiler-turbine dynamics subject to actuator magnitude and rate
      constraints. System nonlinearity is handled by a suitable linear parameter
      varying system representation with drum pressure as the system varying parameter.
      Variation of the drum pressure is represented by suitable norm-bounded
      uncertainty and affine dependence on system matrices. Based on linear matrix
      inequality algorithms, the magnitude and rate constraints on the actuator and the
      deviations of fluid density and water level are formulated while the tracking
      abilities on the drum pressure and power output are optimized. Variation ranges
      of drum pressure and magnitude tracking commands are used as controller design
      parameters, determined according to the boiler-turbine's operation range.

PMID- 22959739
TI  - The cost of mental disorders in France.
AB  - AIMS: To provide burden estimates of mental disorders in France and compare the
      results with findings from other countries and EU in general. METHOD: Stepwise
      top down approach, consisting of analyses of existing data sets, national surveys
      and ad hoc surveys. Mental disorder was defined by diagnoses in the chapter
      'Mental and behavioural disorders' from the International Classification of
      Diseases, tenth revision (ICD-10), excluding, dementia and mental retardation.
      Disease burden was measured by total health care costs, social care costs, lost
      output and loss of well being, 2007 data was used consistently. RESULTS: The
      total cost of mental health care was estimated at ?13.4 billion, or 8% of total
      healthcare expenditures. Total cost of health and social services was estimated
      at ?6.3 billion, including ?1.3 billion for informal care. Total cost of lost
      production amounted to ?24.4 billion, ?20.0 billion for lost output and ?4.4
      billion for workers' compensation. Mental disorders resulted in a total loss of
      2.2 million QALY and a total cost of lost well being of ?65.08 billion. The total
      costs of mental disorders were estimated at ?109 billion, 20% of which are actual
      money spent and 80% the social value of disease consequences. CONCLUSION: In
      France with a population of 65 million, an estimated 12 million inhabitants
      currently suffer from one or more mental disorders. The true size and burden of
      mental disorders in France was significantly underestimated by policy makers in
      the past.

PMID- 22959741
TI  - Improved delay-dependent robust stability criteria for recurrent neural networks
      with time-varying delays.
AB  - In this paper, the problem of improved delay-dependent robust stability criteria
      for recurrent neural networks (RNNs) with time-varying delays is investigated.
      Combining the Lyapunov-Krasovskii functional with linear matrix inequality (LMI)
      techniques and integral inequality approach (IIA), delay-dependent robust
      stability conditions for RNNs with time-varying delay, expressed in terms of
      quadratic forms of state and LMI, are derived. The proposed methods contain the
      least numbers of computed variables while maintaining the effectiveness of the
      stability conditions. Both theoretical and numerical comparisons have been
      provided to show the effectiveness and efficiency of the present method.
      Numerical examples are included to show that the proposed method is effective and
      can provide less conservative results.

PMID- 22959742
TI  - Social cognition in clinical "at risk" for psychosis and first episode psychosis
      populations.
AB  - BACKGROUND: Social cognitive deficits have been demonstrated in first episode
      psychosis (FEP) and groups at high risk for developing psychosis but the relative
      degree of deficit between these groups is unclear. Such knowledge may further our
      understanding of the importance of these deficits in the development of
      psychosis. The study aimed to compare the degree of impairment in social
      cognition in three groups: FEP, those at "ultra high risk" (UHR) for psychosis
      and healthy controls. METHODS: UHR and FEP patients were recruited from an
      established youth mental health service in Melbourne. Three domains of social
      cognition were assessed: ToM (hinting task and interpretation of visual jokes);
      facial and vocal emotion recognition (Diagnostic Assessment of Non Verbal
      Accuracy); social perception (Mayer-Salovey-Caruso Emotional Intelligence Test -
      managing emotions branch). Group differences were analysed using Analysis of
      Covariance with age, gender and IQ as covariates. RESULTS: Data on 30 UHR, 40 FEP
      and 30 control participants were analysed. FEP patients performed significantly
      worse on all social cognition tasks compared to controls. For the UHR group,
      scores were intermediate between FEP and controls for all tasks, but only
      significantly different to controls for ToM tasks. Effects sizes were largest for
      the ToM tasks and the emotion recognition task for both patient groups. There
      were no significant differences between UHR and FEP patients in performance on
      any of the tasks. CONCLUSIONS: Social cognition is generally impaired in FEP
      patients but there are fewer deficits in a UHR group. Longitudinal research in
      larger samples is needed to investigate whether social cognition deficits, such
      as ToM are risk factors in UHR groups for subsequent transition to full-threshold
      psychosis.

PMID- 22959744
TI  - Repairing critical-sized rat calvarial defects with progenitor cell-seeded
      acellular periosteum: a novel biomimetic scaffold.
AB  - BACKGROUND: Many types of scaffolds have been used in bone tissue engineering,
      with none emerging as favorites. We propose the use of acellular periosteum as a
      biologic scaffold to allow for progenitor cell adherence, migration, and
      proliferation in vitro and to test the construct in vivo in a rat calvarial
      defect model. METHODS: Bovine periosteum was processed to remove all antigenic
      material (RTI Biologics), and its cambial layer was then seeded with adipose
      derived stromal cells (ASCs) or periosteal-derived stromal cells (PSCs) and
      incubated for 14 days. Adherence required a fibronectin coat and was verified for
      both cell types via scanning electron microscopy and histology. Two 5-mm diameter
      calvarial defects were created in each of 19 rats. These were filled with
      xenograft bone chips and covered with acellular periosteum in combination with
      cells (ASC or PSC), growth factors (vascular endothelial growth factor, bone
      morphogenetic protein-2, or both), or alone (controls). Rats were killed 56 days
      postoperatively. Bone deposition was quantified by microcomputed tomography, and
      viability was determined histologically. Significance was determined through
      analysis of variance. RESULTS: Acellular allo-periosteum with a fibronectin coat
      permitted ASC and PSC adherence, migration, and proliferation in vitro. In the
      rat calvarial defects, the addition of stem cells (P < .001) and growth factors
      (P < .001) to the acellular periosteum increased de novo bone growth relative to
      controls. Although the stem cell source did not influence revitalization (P =
      .242), the combination of growth factors was more effective (P > .001) than
      either growth factor alone. The interaction indicated that the 2 cell types did
      not respond equally to growth factors (P = .039). CONCLUSION: Acellular allo
      periosteum is a biomimetic scaffold that permits pleuripotent cell adherence,
      migration, and proliferation in vitro. The combination of acellular periosteum,
      xenograft bone, stem cells, and growth factors may prove a viable combination for
      cranial bone tissue engineering.

PMID- 22959743
TI  - Effects of facial emotion recognition remediation on visual scanning of novel
      face stimuli.
AB  - Previous research shows that emotion recognition in schizophrenia can be improved
      with targeted remediation that draws attention to important facial features
      (eyes, nose, mouth). Moreover, the effects of training have been shown to last
      for up to one month after training. The aim of this study was to investigate
      whether improved emotion recognition of novel faces is associated with
      concomitant changes in visual scanning of these same novel facial expressions.
      Thirty-nine participants with schizophrenia received emotion recognition training
      using Ekman's Micro-Expression Training Tool (METT), with emotion recognition and
      visual scanpath (VSP) recordings to face stimuli collected simultaneously.
      Baseline ratings of interpersonal and cognitive functioning were also collected
      from all participants. Post-METT training, participants showed changes in foveal
      attention to the features of facial expressions of emotion not used in METT
      training, which were generally consistent with the information about important
      features from the METT. In particular, there were changes in how participants
      looked at the features of facial expressions of emotion surprise, disgust, fear,
      happiness, and neutral, demonstrating that improved emotion recognition is
      paralleled by changes in the way participants with schizophrenia viewed novel
      facial expressions of emotion. However, there were overall decreases in foveal
      attention to sad and neutral faces that indicate more intensive instruction might
      be needed for these faces during training. Most importantly, the evidence shows
      that participant gender may affect training outcomes.

PMID- 22959745
TI  - [Fanconi anemia in 2012: diagnosis, pediatric follow-up and treatment].
AB  - Fanconi anemia (FA) is a rare genetic disease, transmitted in an autosomal
      recessive mode. The clinical phenotype is very broad and heterogeneous, related
      to the wide range of genes involved in this pathology. The classical triad of
      short height, physical abnormalities, and bone marrow failure is suggestive. The
      main physical abnormalities found involve the limbs, spinal column, skin, kidneys
      and urinary tract, and the ORL zone. Recent progress in molecular biology has
      identified 15 genes whose mutation causes FA chromosomal instability. FA is
      diagnosed by cytogenetic examination, then specified by molecular analysis. As FA
      patients may present multiorgan abnormalities and a high risk for neoplasia
      development, their medical follow-up has to be multidisciplinary and prolonged
      throughout life. The main challenges of the follow-up are patient information and
      education. Bone marrow failure, appearing during the first decade, requires close
      hematological monitoring and for severe cases requires hematopoietic stem cell
      transplantation, major and specific care with frequent serious complications and
      high mortality, but this is the only curative treatment in FA. Extrahematological
      care consists in screening for organ abnormalities and defects as well as
      monitoring precancerous lesions and tumors.

PMID- 22959746
TI  - Changes of elbow muscle moment arms after total elbow arthroplasty.
AB  - The changes of muscle moment arms on the elbow during simulated active motion
      were calculated from the simultaneous kinematic and tendon excursion in six
      cadaver specimens. The results after four different Coonrad-Morrey total elbow
      arthroplasty positions of implantation were compared with those of the intact
      elbow. With optimal total elbow arthroplasty implantation, the general pattern of
      change of the muscle moment arms with elbow flexion resembled that of the intact
      elbow, but with increased flexor dominance over the extensors with elbow flexion.
      No significant modification of the muscle moment arms was related to the changes
      of positioning of the implants, except with 60 degrees  elbow flexion, a slight
      increase of the brachialis muscle moment arms with distal placement of the
      humeral component. The malplacements of the humeral component in varus/valgus or
      in internal/external rotation were found to significantly affect the muscle
      moment arms.

PMID- 22959747
TI  - Elbow lengthening after total prosthetic arthroplasty: Observations and clinical
      implications.
AB  - We have carried out a radiologic study to determine the effect on limb length of
      inserting the components of a total elbow joint replacement arthroplasty. The
      preoperative and postoperative radiographs of 27 consecutive patients undergoing
      total elbow joint replacement arthroplasty with the Kudo prosthesis were studied.
      In all cases lengthening across the elbow was found. Both ulnar and humeral
      lengthening were observed. A mean length increase of 8.6 mm (range 2 to 17 mm)
      was recorded. Ulnar lengthening contributed to overall lengthening by a
      significantly greater amount than humeral lengthening. We correlated the degree
      of lengthening observed with clinical measurements in this series of patients but
      found no significant differences. Operative maneuvers are suggested to
      accommodate this length increase, to achieve soft-tissue balance, and to avoid
      potential complications such as ulnar neuropathy and joint instability.

PMID- 22959748
TI  - Dynamic examination techniques in shoulder instability.
AB  - We prospectively examined 25 patients with recurrent shoulder dislocation before
      surgical stabilization. On the basis of preoperative and intraoperative findings,
      a preliminary working diagnosis was established; anterior dislocation in 14
      patients, posterior dislocation in 4, and unclassified dislocation in 7.
      Glenohumeral joint laxity was subsequently assessed by clinical examination,
      fluoroscopy, and ultrasonography in all patients and in a control group of 25
      subjects without shoulder disease. Normal laxity was defined as humeral head
      displacement not exceeding the standard deviation of the mean in the control
      group. Ultrasonographic findings were poorly reproducible and concurred with the
      results of clinical examination in only 4 patients and with fluoroscopic results
      in 7 patients. Clinical examination and fluoroscopic findings were reproducible
      and were identical in 19 patients. Laxity was present in 23 shoulders at clinical
      examination and in 18 shoulders at fluoroscopic examination. The preliminary
      working diagnosis was confirmed in 10 patients by clinical examination and in 6
      patients by fluoroscopy. Previously unknown laxity was revealed by clinical
      examination in 13 and by fluoroscopy in 11 shoulders. Glenohumerol joint laxity
      should be evaluated before the operation by clinical and fluoroscopic
      examinations and must be taken into account in the operative techniques used to
      achieve stability.

PMID- 22959749
TI  - In vivo quantification of the laxity of normal and unstable glenohumeral joints.
AB  - The purpose of this study was to determine whether the magnitude of glenohumeral
      translation on clinical laxity tests could distinguish between clinically stable
      shoulders and shoulders with traumatic or atraumatic instability. Subjects
      included eight male volunteers with no history of symptoms of glenohumeral
      instability, eight patients with documented traumatic anterior instability and
      Bankart lesions, and eight patients with documented atraumatic multidirectional
      instability. The patients in the two instability groups had disabling instability
      that was refractory to nonoperative management and thus met the indications for
      surgical repair. All subjects were examined by an experienced shoulder surgeon
      using five standard manual tests: anterior drawer, posterior drawer, sulcus, push
      pull, and fulcrum. The glenohumeral translations occurring during these laxity
      tests were quantitated with a spatial sensing system that had six degrees of
      freedom and was rigidly fixed to the scapula and humerus. The result showed
      substantial overlap in the translations found in members of the three groups for
      each of the laxity tests. Standard laxity tests demonstrate considerable
      translation in normal glenohumeral joints and do not reliably differentiate
      normal shoulders from those with two common forms of glenohumeral instability.
      This study suggests that assessment of the magnitude of glenohumeral translation
      on clinical laxity tests is not a specific test for the diagnosis of glenohumeral
      instability. Healthy subjects without symptoms may have as much translation as
      patients needing surgical repair for symptomatic shoulder instability. The need
      for and the type of surgical reconstruction for the unstable shoulder must be
      based on the patient's history and on duplication of the symptoms of instability
      on directed physical examination rather than on the magnitude of glenohumeral
      translation.

PMID- 22959750
TI  - An anatomic study of the subscapularis tendon and myotendinous junction.
AB  - The subscapularis muscle and tendon were studied in 25 cadaveric specimens. The
      subscaputaris insertion into the proximal humerus and its musculolendinous
      junction was defined. We found that the subscapularis muscle had a gradual
      formation of the musculotendinous junction and, in contrast to classical
      descriptions, inserted into the humerus as both tendon and muscle. The
      musculotendinous junction was fully formed 2 cm from the lesser tuberosity. The
      superior 60% of the muscle's insertion inserted into the lesser tuberosity as
      tendon. The remaining insertion consisted of muscle and was below the lesser
      tuberosity. The anterior humeral circumflex vessels and the axillary nerve marked
      the inferior aspect of the subscapularis muscle at the anterior aspect of the
      quadrangular space. The vessels then coursed laterally and superiorly onto the
      anterior surface of the muscle insertion coursing over the division between the
      tendinous and muscular portions. Proper identification of these relationships can
      prevent complications in shoulder surgery.

PMID- 22959751
TI  - Adverse reactions to an absorbable shoulder fixation device.
AB  - Bioabsorbable implants have been advocated for use in repair of a torn glenoid
      labrum to correct shoulder instability. These implants have been thought to be
      safe and to have little toxicity, antigenicity, or adverse side effects. However,
      similar implants have been shown to cause nonspecific granulomatous reactions
      when implanted into bone or soft tissues in studies in both animals and human
      beings. This article reports the adverse effects of these implants in six
      shoulders of five patients who had repair of a damaged glenoid labrum. All
      patients reported increasing pain and loss of shoulder motion after insertion of
      these devices. All required a further arthroscopic lavage and debridement to
      reduce the inlracapsular synovitis. Granulomatous reactions were identified
      histologically in all cases. No long-term side effects were encountered, and all
      patients recovered satisfactorily.

PMID- 22959752
TI  - Distribution of bone mineral density and bone strength of the proximal humerus.
AB  - Clinical experience led us to the hypothesis that in the proximal humerus
      cancellous bone beneath the top part of the head is the strongest and the bone of
      the humeral neck is the weakest. This hypothesis was examined on dissected
      proximal humeri with bone mineral densitometry and an indention test. Both dual
      photon absorptiometry and bone mineral analyses confirmed that the top part of
      the humeral head was the region with the greatest amount of bone mineral. The
      humeral neck had approximately one half the bone mineral density of the humeral
      head. The cancellous bone of the neck had only one third the mechanical strength
      of the humeral head on the indention test. The high degree of osteoporosis of the
      neck region increases the difficulty of surgical treatment for displaced humeral
      neck fractures.

PMID- 22959753
TI  - Loss of the deltoid after shoulder operations: An operative disaster.
AB  - A series of 36 patients who had a postoperative loss of the anterior or anterior
      lateral deltoid muscle after shoulder operations (i.e., acromioplasties, anterior
      shoulder reconstructions, or arthroplasty procedures) was referred to the senior
      author. Three patients last the function of their deltoid after an injury to the
      axillary nerve, and 33 patients lost deltoid function after loss of the origin of
      the deltoid from the clavicle and acromion. All patients were significantly
      disabled. All patients were dissatisfied with the result of the previous
      operation, and eight patients experienced painful anterior or anterior/superior
      dislocation of the glenohumeral joint. Treatment was nonspecific and supportive.
      The authors conclude that loss of anterior deltoid function secondary to
      denervation or detachment results in irrevocable pain and impairment of function.
      Careful attention to the surgical technique of deltoid reattachment and
      protection of the axillary nerve are essential to the prevention of dire
      consequences to shoulder function.

PMID- 22959754
TI  - The bow test for the subacromial impingement syndrome.
AB  - Because of the biomechanics of the glenohumeral joint, impairment of rotator cuff
      function leads to cranial migration of the humeral head, impinging the greater
      tubercle against the coraco-acromial arch and irritating the subacromial bursa.
      When bursal irritation has become established, active elevation of the arm
      against gravity will cause pain within an arc of motion. When a patient with a
      painful arc is asked to bend forward and let the arm hang, the same arc will
      become painless. This noninvasive clinical test called the "bow test" is a simple
      means by which subacromial impingement can be clinically identified as the source
      of pain in the painful arc of shoulder motion.

PMID- 22959755
TI  - Acromial fracture: A complication of arthroscopic subacromial decompression.
AB  - For many surgeons arthroscopic subacromial decompression has replaced open
      surgery for the treatment of refractory impingement syndrome. A newly recognized
      complication of this procedure is fracture of the acromion process. Six patients
      presented with reports of increasing postoperative shoulder pain, commonly with a
      history of sudden onset during physical therapy. Diagnosis was frequently
      delayed; three of the six fractures were identifiable only on axillary
      radiographs. Disability varied from mild pain to severe functional impairment,
      depending on fracture size and location. Treatment modalities ranged from total
      acromionecfomy to conservative measures; most results were poor. These cases
      suggest that: (1) risk factors for experiencing an acromial fracture include
      osteopenia and overzealous bone resection; (2) surgical correction of the
      fracture may not satisfactorily resolve associated pain and loss of range of
      motion; and (3) emphasis on appropriate preoperative planning and meticulous
      surgical technique to minimize bony resection may decrease the risk of this
      compficafion and its resultant disability.

PMID- 22959756
TI  - Stress fracture of the acromion.

PMID- 22959757
TI  - Solitary osteochondroma of the distal clavicle causing a full-thickness rotator
      cuff tear.

PMID- 22959758
TI  - Intraarticular osteochondroma of the elbow.

PMID- 22959760
TI  - Pathologic femur fracture due to a brown tumor in a patient with secondary
      hyperparathyroidism and vitamin D-resistant rickets.
AB  - Vitamin D-resistant rickets is the common clinical outcome of multiple genetic
      mutations that alter the regulation of phosphorus and vitamin D metabolism,
      mainly through their effects on fibroblast growth factor 23 (FGF-23). These
      diseases typically present in childhood with the classic physical examination
      finding of nutritional rickets, such as genu varum/valgum and rachitic rosary.
      Treatment, which is aimed at improving severe bone disease with vitamin D and
      phosphorus supplementation, can cause secondary hyperparathyroidism and/or kidney
      failure from nephrocalcinosis over the life of the patient. Although FGF-23 has
      been shown to downregulate parathyroid hormone in vitro, its effect on
      parathyroid secretion in disease states such as chronic kidney disease and X
      linked hypophosphatemic rickets is unclear because elevations in FGF-23 and
      parathyroid hormone levels characterize both of these disease states. We describe
      a case of vitamin D-resistant rickets that presented with a femur fracture
      through a brown tumor. Radiographs show the combination of severe bony
      abnormalities associated with both long-standing hyperparathyroidism and vitamin
      D-resistant rickets.

PMID- 22959759
TI  - Follicular T-cell lymphoma: a member of an emerging family of follicular helper T
      cell derived T-cell lymphomas.
AB  - Unlike B-cell lymphomas, where knowledge of normal B-cell origin and
      differentiation has greatly contributed to their classification, the current
      classification of peripheral T-cell lymphomas is limited by a lack of
      understanding of their cellular origin. In the current World Health Organization
      classification of lymphomas, follicular T-cell lymphoma was formally recognized
      as a morphologic variant of peripheral T-cell lymphoma, not otherwise specified.
      There is growing evidence, however, that follicular T-cell lymphoma may be a
      unique clinicopathologic entity based on its morphologic features and derivation
      from follicular helper T-cells. In addition, there are abundant recent data
      supporting the concept that follicular helper T-cells can give rise to other
      types of T-cell lymphoma, including angioimmunoblastic T-cell lymphoma, primary
      cutaneous CD4+ small/medium T-cell lymphoma, and a subset of neoplasms, in
      addition to follicular T-cell lymphoma, currently classified as peripheral T-cell
      lymphoma, not otherwise specified. In this review, we focus primarily on the
      clinicopathologic, immunophenotypic, and molecular features of follicular T-cell
      lymphoma and discuss its potential relationship with other types of T-cell
      lymphoma thought to be derived from follicular helper T-cells.

PMID- 22959761
TI  - A clinical approach to the treatment of chronic hypernatremia.
AB  - Hypernatremia is a commonly encountered electrolyte disorder occurring in both
      the inpatient and outpatient settings. Community-acquired hypernatremia typically
      occurs at the extremes of age, whereas hospital-acquired hypernatremia affects
      patients of all age groups. Serum sodium concentration is linked to water
      homeostasis, which is dependent on the thirst mechanism, arginine vasopressin,
      and kidney function. Because both hypernatremia and the rate of correction of
      hypernatremia are associated with significant morbidity and mortality, prompt
      effective treatment is crucial. Chronic hypernatremia can be classified into 3
      broad categories, hypovolemic, euvolemic, and hypervolemic forms, with each form
      having unique treatment considerations. In this teaching case, we provide a
      clinically based quantitative approach to the treatment of both hypervolemic and
      hypovolemic hypernatremia, which occurred in the same patient during the course
      of a prolonged illness.

PMID- 22959762
TI  - Is polycystic ovary syndrome another risk factor for venous thromboembolism?
      United States, 2003-2008.
AB  - OBJECTIVE: We sought to determine prevalence and likelihood of venous
      thromboembolism (VTE) among women with and without polycystic ovary syndrome
      (PCOS). STUDY DESIGN: We performed a cross-sectional analysis using Thomson
      Reuters MarketScan Commercial databases for the years 2003 through 2008. The
      association between VTE and PCOS among women aged 18-45 years was assessed using
      age-stratified multivariable logistic regression models. RESULTS: Prevalence of
      VTE per 100,000 was 374.2 for PCOS women and 193.8 for women without PCOS.
      Compared with women without PCOS, those with PCOS were more likely to have VTE
      (adjusted odds ratio [aOR] 18-24 years, 3.26; 95% confidence interval [CI], 2.61
      4.08; aOR 25-34 years, 2.39; 95% CI, 2.12-2.70; aOR 35-45 years, 2.05; 95% CI,
      1.84-2.38). A protective association (odds ratio, 0.8; 95% CI, 0.73-0.98) with
      oral contraceptive use was noted for PCOS women. CONCLUSION: PCOS might be a
      predisposing condition for VTE, particularly among women aged 18-24 years. Oral
      contraceptive use might be protective.

PMID- 22959764
TI  - Fertility preservation in women of reproductive age with cancer.
AB  - Advances in cancer care have improved survival, driving the need to mitigate the
      side effects of cancer therapy to improve the quality of life of cancer
      survivors. Use of fertility preservation has grown given the potential
      gonadotoxicity of chemotherapy and radiation, the increasing rate of treatment
      success, and the strong desire for childbearing in cancer survivors. Current
      options include embryo and oocyte cryopreservation, ovarian tissue
      cryopreservation, gonadal suppression, and ovarian transposition. Consultation
      with a reproductive endocrinology and infertility specialist trained in fertility
      preservation provides cancer patients an individualized risk assessment for
      future gonadal failure and discussion of potential fertility preservation
      options.

PMID- 22959765
TI  - Evaluation of dimerization-inhibitory activities of cyclic peptides containing a
      beta-hairpin loop sequence of the EGF receptor.
AB  - Structure-activity relationships of cyclic peptides mimicking the beta-hairpin
      structure of the 'dimerization arm' at residues 242-259 of the EGF receptor are
      examined. Cyclic peptides containing the arm head of the beta-hairpin loop showed
      inhibitory activity toward the EGF receptor's dimerization. Cyclic peptides
      containing a Retro-Inverso sequence of the dimerization arm showed clear
      inhibitory effects on the dimerization in vitro and efficiently suppressed the
      proliferation of A431 cells, which abundantly express the EGF receptor on their
      surface. The effects at a specific hydrophobic site of the loop structure were
      expected to enhance the interactions with the receptor.

PMID- 22959763
TI  - Relationship between 17-hydroxyprogesterone caproate concentrations and
      gestational age at delivery in twin gestation.
AB  - OBJECTIVE: We sought to evaluate in women with twin gestation the relationship
      between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational
      age at delivery and select biomarkers of potential pathways of drug action. STUDY
      DESIGN: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch
      2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age
      at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone,
      C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed.
      RESULTS: Women with higher concentrations of 17-OHPC delivered at earlier
      gestational ages than women with lower concentrations (P < .001). Women receiving
      17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in
      epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in
      both groups. A highly significant (P < .0001) positive relationship was observed
      between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone
      concentrations at both epochs. Corticotropin-releasing hormone concentrations did
      not differ by treatment group. CONCLUSION: 17-OHPC may adversely impact
      gestational age at delivery in women with twin gestation.

PMID- 22959766
TI  - Possible conformation of amphotericin B dimer in membrane-bound assembly as
      deduced from solid-state NMR.
AB  - Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in
      membrane, a covalent dimer was synthesized between (13)C-labled AmB methyl ester
      and (19)F-labled AmB. The dimer showed slightly weaker but significant biological
      activities against fungi and red blood cells compared with those of monomeric
      AmB. Then the dimer was subjected to (13)C{(19)F}REDOR (Rotational-Echo Double
      Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing
      effects were explained by two components; a short (13)C/(19)F distance (6.9A)
      accounting for 23% of the REDOR dephasing, and a longer one (14A) comprising the
      rest of the dephasing. The shorter distance is likely to reflect the formation of
      barrel-stave ion channel.

PMID- 22959767
TI  - Studies on synthesis and activation mechanism of mitomycin dimers connected by
      1,2-dithiolane and diol linkers.
AB  - We report the synthetic and mechanistic studies on a new cyclic disulfide
      mitomycin dimer, 7-N,7'-N'-(1",2"-dithiolanyl-3",5"-dimethylenyl)bismitomycin C
      (8), and a diol mitomycin dimer, 7-N,7'-N'-(2",4"-dihydroxy-1",5"
      pentanediyl)bismitomycin C (9). Mitomycin 8 is a dimer connected by a 1,2
      dithiolane (a five-membered cyclic disulfide) linker, and was specifically
      designed to undergo nucleophilic activation and double DNA alkylations leading to
      efficient production of DNA interstrand cross-link (DNA ISC) adducts. Disulfide
      cleavage in 8 would generate two thiol groups that could serve as probes to
      activate two mitomycin rings. At first, the target mitomycin 8 was synthesized
      using mitomycin A (1) and the key intermediate, cyclic disulfide (10), which was
      prepared through a seven-step synthetic sequence. Diol mitomycin 9 was also
      synthesized from 1 and diamine salt 13. Next, kinetic studies using solvolysis
      reaction revealed that the activation rates of 8 were much higher than those of 9
      and mitomycin C (2) under nucleophilic conditions provided by Et(3)P presumably
      due to the presence of a cyclic disulfide unit in 8. These findings led us to
      propose a nucleophilic activation pathway for 8. Then, DNA ISC experiments
      further revealed that the levels of DNA ISC caused by 8 in the presence of Et(3)P
      were much higher (97%) than those by 9 (5%) and 2 (4%). More importantly,
      mitomycin 8 underwent much faster activation and produced slightly higher levels
      of DNA ISC than the previously reported mitomycins 5-7. Overall, we concluded
      that 8 was highly efficient for both nucleophilic activation and corresponding
      DNA ISC formation, and that this differentiation came from the crucial function
      of the cyclic disulfide unit in 8.

PMID- 22959768
TI  - Rising U.S. income inequality and the changing gradient of socioeconomic status
      on physical functioning and activity limitations, 1984-2007.
AB  - This study examines the interactive contextual effect of income inequality on
      health. Specifically, we hypothesize that income inequality will moderate the
      relationships between individual-level risk factors and health. Using National
      Health Interview Survey data 1984-2007 (n = 607,959) and U.S. Census data, this
      paper estimates the effect of the dramatic increase in income inequality in the
      U.S. over the past two decades on the gradient of socioeconomic status on two
      measures of health (i.e., physical functioning and activity limitations). Results
      indicate that increasing income inequality strengthens the protective effects of
      family income, employment, college education, and marriage on these two measures
      of health. In contrast, high school education's protective effect (relative to
      less than a high school education) weakens in the context of increasing income
      inequality. In addition, we find that increasing income inequality exacerbates
      men's disadvantages in physical functioning and activity limitations. These
      findings shed light on research about growing health disparities in the U.S. in
      the last several decades.

PMID- 22959769
TI  - Development of a quantitative diagnostic method of estrogen receptor expression
      levels by immunohistochemistry using organic fluorescent material-assembled
      nanoparticles.
AB  - The detection of estrogen receptors (ERs) by immunohistochemistry (IHC) using
      3,3'-diaminobenzidine (DAB) is slightly weak as a prognostic marker, but it is
      essential to the application of endocrine therapy, such as antiestrogen tamoxifen
      based therapy. IHC using DAB is a poor quantitative method because horseradish
      peroxidase (HRP) activity depends on reaction time, temperature and substrate
      concentration. However, IHC using fluorescent material provides an effective
      method to quantitatively use IHC because the signal intensity is proportional to
      the intensity of the photon excitation energy. However, the high level of
      autofluorescence has impeded the development of quantitative IHC using
      fluorescence. We developed organic fluorescent material (tetramethylrhodamine)
      assembled nanoparticles for IHC. Tissue autofluorescence is comparable to the
      fluorescence intensity of quantum dots, which are the most representative
      fluorescent nanoparticles. The fluorescent intensity of our novel nanoparticles
      was 10.2-fold greater than quantum dots, and they did not bind non-specifically
      to breast cancer tissues due to the polyethylene glycol chain that coated their
      surfaces. Therefore, the fluorescent intensity of our nanoparticles significantly
      exceeded autofluorescence, which produced a significantly higher signal-to-noise
      ratio on IHC-imaged cancer tissues than previous methods. Moreover,
      immunostaining data from our nanoparticle fluorescent IHC and IHC with DAB were
      compared in the same region of adjacent tissues sections to quantitatively
      examine the two methods. The results demonstrated that our nanoparticle staining
      analyzed a wide range of ER expression levels with higher accuracy and
      quantitative sensitivity than DAB staining. This enhancement in the diagnostic
      accuracy and sensitivity for ERs using our immunostaining method will improve the
      prediction of responses to therapies that target ERs and progesterone receptors
      that are induced by a downstream ER signal.

PMID- 22959770
TI  - Expression and function of the atypical cadherin FAT1 in chronic liver disease.
AB  - Hepatic fibrosis can be considered as wound healing process in response to
      hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event
      of hepatic fibrosis since activated HSCs are the cellular source of enhanced
      extracellular matrix deposition, and reversion of liver fibrosis is accompanied
      by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been
      shown to regulate diverse biological functions as cell proliferation and planar
      cell polarity, and also to affect wound healing. Here, we found increased FAT1
      expression in different murine models of chronic liver injury and in cirrhotic
      livers of patients with different liver disease. Also in hepatic tissue of
      patients with non-alcoholic steatohepatitis FAT1 expression was significantly
      enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry
      revealed no significant differences in staining intensity between hepatocytes in
      normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa
      of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and
      protein expression markedly increased during in vitro activation of primary human
      and murine HSCs. Together, these data indicated activated HSCs as cellular source
      of enhanced FAT1 expression in diseased livers. To gain insight into the
      functional role of FAT1 in activated HSCs we suppressed FAT1 in these cells by
      siRNA. We newly found that FAT1 suppression in activated HSCs caused a
      downregulation of NFkappaB activity. This transcription factor is critical for
      apoptosis resistance of HSCs, and consequently, we detected a higher apoptosis
      rate in FAT1 suppressed HSCs compared to control cells. Our findings suggest FAT1
      as new therapeutic target for the prevention and treatment of hepatic fibrosis in
      chronic liver disease.

PMID- 22959771
TI  - Differentiation of lipsticks by Raman spectroscopy.
AB  - Dispersive Raman spectra have been obtained using a Raman microscope and an
      excitation wavelength of 632.8 nm from 69 lipsticks of various colours and from a
      range of manufacturers without any pre-treatment of the samples. 10% of the
      samples were too fluorescent to give Raman spectra. 22% of the samples gave
      spectra which were unique to the brand and colour within the collected sample
      set. The remaining 68% of the samples gave spectra which could be classified into
      seven distinct groups. Discrimination of red lipsticks by this technique was the
      most difficult. The spectra of deposited lipstick samples remained unchanged over
      a period of a least a year.

PMID- 22959773
TI  - Application of Doehlert uniform shell designs for selecting optimal amounts of
      internal standards in the analysis of prostaglandins and leukotrienes by liquid
      chromatography-tandem mass spectrometry.
AB  - A protocol for the analysis of multiple prostaglandins and leukotrienes in cell
      culture media by using multiple internal standards was validated. A two-factor
      Doehlert design was used to determine the behaviour of the relationship
      analyte/internal standard (namely: PGE2/PGE2-d4, PGE3/PGE2-d4, LTB4/LTB4-d4 and
      LTB5/LTB4-d4) and to select the optimal amounts of deuterated internal standards
      for quantifying simultaneously the prostaglandins and leukotrienes in cell
      culture media by LC-MS/MS. The selection of optimal amounts of internal standards
      was based on mathematical models that allow visualizing concentration regions
      where the response factors remain constant over a wide range of analytical
      concentrations. The linearity of the calibration curves for each analyte at the
      optimal levels suggested by the mathematical models was statistically confirmed
      by means of the ratio lack-of-fit to pure error. The validated protocol was
      successfully applied in the simultaneous quantification of pro- and anti
      inflammatory eicosanoids in stimulated cod head kidney cell culture media. The
      two-factor Doehlert design has permitted to estimate the experimental response as
      a function of six variables (PGE2, PGE3, LTB4, LTB5, PGE2-d4 and LTB4-d4) which
      represents a substantial reduction of resources, time and experiments of
      approximately 84% (7*3 experiments) when compared with the full six-factor
      Doehlert design (43*3 experiments).

PMID- 22959772
TI  - Staphylococcus aureus nasal carriage during the infectious diseases national
      congress in France.
AB  - OBJECTIVE: Screening for (methicillin-sensitive [MSSA] or -resistant [MRSA])
      Staphylococcus aureus (SA) nasal carriage in health care workers in contact with
      fragile patients is a recurrent question. We wanted to assess carriage among
      infectious diseases healthcare workers. METHODS: Voluntary health care workers
      were recruited during the 2010 Yearly French Congress (Journees Nationales
      d'Infectiologie, JNI). An anonymous double nasal swab was performed followed by
      PCR examination (GeneXpert MRSA/SA nasal tests) carried out on the Cepheid stand.
      Health care workers were also asked to fill in a questionnaire. Results were
      available 1 hour later but kept anonymous. RESULTS: One hundred and fifty-two
      tests and questionnaires were selected. MRSA was isolated from four health care
      workers (2.4%). MSSA was isolated from 52 health care workers (34.2%). Sex,
      clinical activity of health care workers, hospital size, and systematic screening
      of patients did not affect carriage. CONCLUSIONS: The prevalence of MSSA in nasal
      carriage in France is similar to the European one but the prevalence of MRSA is
      higher. This raises the question of a targeted decolonization in health care
      workers.

PMID- 22959774
TI  - Simultaneous determination of 10 beta2-agonists in swine urine using liquid
      chromatography-tandem mass spectrometry and multi-walled carbon nanotubes as a
      reversed dispersive solid phase extraction sorbent.
AB  - A simple and inexpensive pretreatment procedure was developed for 10 beta2
      agonists (clenbuterol, ractopamine, salbutamol, bambuterol, penbuterol,
      tulobuterol, clorprenaline, mabuterol, cimaterol and terbutaline) in swine urine
      using dispersive solid phase extraction (dSPE) with multi-walled carbon nanotubes
      (MWCNTs). The sample was analysed after purification by ultra high performance
      liquid chromatography-positive electrospray ionisation tandem mass spectrometry
      (UHPLC-ESI-MS/MS). The pH value of the swine urine, extraction time, type and
      amount of MWCNTs and type of eluent were optimised to increase the sample
      throughput and sensitivity. The samples were quantified using clenbuterol-D9,
      ractopamine-D6 and salbutamol-D3 as internal standards. The recoveries of the
      target compounds from swine urine samples at pH 10.0 were most efficient when
      using 20 mg of MWCNTs with a 30-50 nm outer diameter and a length of 10-30 MUm,
      while a mixture of water/methanol (90:10, v/v) with 0.5% formic acid was shown to
      be the most suitable solvent for desorbing the compounds from the MWCNTs. The
      proposed method was validated according to the European Commission Decision
      2002/657/EC, which determines linearity, specificity, decision limit (CCalpha),
      detection capability (CCbeta), recovery, precision and stability.

PMID- 22959775
TI  - Recent developments in liquid chromatography-mass spectrometry and related
      techniques.
AB  - This review summarizes the state-of-art in liquid chromatography-mass
      spectrometry (LC-MS) and related techniques with the main focus on recent
      developments in the last decade. LC-MS records an enormous growth in recent years
      due to the application potential in analytical chemistry, biochemistry,
      pharmaceutical analysis, clinical analysis and many other fields, where the
      qualitative and quantitative characterization of complex organic, bioorganic and
      organometallic mixtures is needed. Beginners and moderately experienced LC-MS
      users may be confused by the number of different LC-MS systems on the market,
      therefore an actual overview of mass spectrometers designed for the LC-MS
      configuration and matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) from main manufacturers is compiled here together with an independent
      assessment of their advantages and limitations. Current trends in terms of mass
      analyzers, ionization techniques, fast LC-MS, LC-MALDI-MS, ion mobility
      spectrometry used in LC-MS, quantitation issues specific to MS and emerging mass
      spectrometric approaches complementary to LC-MS are discussed as well.

PMID- 22959776
TI  - Foreword.

PMID- 22959777
TI  - Otoferlin: a multi-C2 domain protein essential for hearing.
AB  - Sound is encoded at synapses between cochlear inner hair cells and the auditory
      nerve. These synapses are anatomically and functionally specialized to transmit
      acoustic information with high fidelity over a lifetime. The molecular mechanisms
      of hair-cell transmitter release have recently attracted substantial interest.
      Here we review progress toward understanding otoferlin, a multi-C2 domain protein
      identified a decade ago by genetic analysis of human deafness. Otoferlin
      functions in hair-cell exocytosis. Several otoferlin C2 domains bind to Ca2+,
      phospholipids, and proteins. Current research reveals requirements for otoferlin
      in priming and fusion of synaptic vesicles during sound encoding. Understanding
      the molecular mechanisms through which otoferlin functions also has important
      implications for understanding the disease mechanisms that lead to deafness.

PMID- 22959778
TI  - Glutathione S-transferase alpha 1 risk polymorphism and increased bilateral
      thalamus mean diffusivity in schizophrenia.
AB  - Oxidative damage in brain cells is one of the factors hypothesized to be involved
      in the pathogenesis of schizophrenia. Glutathione S-transferase (GST) A1*B
      polymorphism, a genotype associated with a higher risk of oxidative damage, is
      associated with increased frequency of schizophrenia diagnosis. Thus, here we
      studied Glutathione S-transferase (GST) A1 polymorphism and diffusion tensor
      imaging-mean diffusivity (MD) data on deep grey matter brain structures in 56
      patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revised (DSM-IV-TR) schizophrenia. Clinical diagnosis and
      psychopathological symptom severity were assessed by using the Structured
      Clinical Interview for DSM-IV-TR (SCID-P) and the Scales for Assessment of
      Positive and Negative Symptoms (SAPS and SANS). Results confirmed that patients
      with schizophrenia who were carriers of the GSTA1 *B risk allele had an increased
      MD in bilateral thalami and increased severity of auditory and global
      hallucinations in comparison with non-B carriers. Thus, oxidative stress
      associated factors may be implicated in specific mechanisms of schizophrenia such
      as altered microstructure of the thalami and specific psychopathological features
      of auditory hallucinations.

PMID- 22959779
TI  - Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on
      bisphosphonate treatment vs no treatment.
AB  - Complex pathways affect bone metabolism at the cellular level, and a balance
      between osteoblast and osteoclast activity is critical to bone remodeling. One of
      the major pathways affecting bone metabolism is Wnt/beta-catenin signaling, and
      its disturbances lead to a wide range of bone abnormalities. An important
      antagonist of this pathway is Dickkopf-1 (Dkk1). Higher Dkk1 levels have been
      associated with increased bone loss due to inhibition of Wnt pathway. Currently,
      bisphosphonates are the most commonly used agents to treat primary osteoporotic
      patients. This study demonstrates the effect of bisphosphonates on Dkk1 levels
      and its correlation with bone mineral density (BMD). Eighty patients with low BMD
      were recruited and divided into 2 groups of 40 each (bisphosphonate treatment
      group and control group). The mean Dkk1 level in the treatment group was
      significantly reduced to 2358.18 vs 3749.80 pg/mL in the control group (p<0.001).
      Pearson correlation coefficient showed negative correlation between Dkk1 and BMD
      at lumbar spine (r=-0.55) and femoral neck in the control group; however, no such
      correlation was found in the treatment group (r=-0.05). Hence, bisphosphonate
      therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in
      such patients.

PMID- 22959780
TI  - [Domiciliary mechanical ventilation in children: a Spanish multicentre study].
AB  - INTRODUCTION: Domiciliary mechanical ventilation (DMV) use is increasing in
      children. Few studies have analysed the characteristics of patients using this
      technique. MATERIALS AND METHODS: An observational, descriptive, transversal,
      multicentre study was conducted on patients between 1 month and 16 years of age
      dependent on domiciliary mechanical ventilation. RESULTS: A total of 163 patients
      with a median age of 7.6 years from 17 Spanish hospitals were studied. The main
      reasons for DMV were neuromuscular disorders. The median age at beginning of DMV
      was 4.6 years. Almost three-quarters (71.3%) received non-invasive ventilation.
      Patients depending on invasive ventilation were younger, started DMV at an
      earlier age, and had more hours of mechanical ventilation per day. The large
      majority (80.9%) used DMV during sleep time only, and 11.7% during the whole day.
      Only 3.4% of patients had external health assistance. Just under half (48.2%)
      were being followed up in specific DMV or multidisciplinary clinics. Almost three
      quarters (72.1%) of patients attended school (42.3% with adapted schooling). Only
      47.8% of school patients had specific caregivers in their schools. CONCLUSIONS:
      DMV in children is used in a very heterogeneous group of patients, and in an
      important number of patients it is started before the third year of life. Despite
      there being a significant proportion of patients with a high dependency on DMV,
      few families receive specific support at home or at school, and health care
      surveillance is variable and poorly coordinated.

PMID- 22959782
TI  - The effects of high-load strength training with protein- or nonprotein-containing
      nutritional supplementation in patients undergoing dialysis.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of high-load
      strength training and protein intake in patients undergoing dialysis with a focus
      on muscle strength, physical performance, and muscle morphology. DESIGN: This was
      a randomized controlled study conducted in three dialysis centers. SUBJECTS:
      Subjects for the study included 29 patients undergoing dialysis. INTERVENTION:
      The participants went through a control period of 16 weeks before completing 16
      weeks of strength training. Before the training period, the participants were
      randomly assigned to receive a protein or a nonprotein drink after every training
      session. MAIN OUTCOME MEASURE: Muscle strength and power were tested using the
      good strength equipment and the leg extensor power rig. Physical performance and
      function were assessed using a chair stand test and the Short Form 36
      questionnaire. Muscle fiber type size and composition were analyzed in biopsies
      obtained from the m. vastus lateralis. RESULTS: All variables remained unchanged
      during the control period. After training, muscle strength and power, physical
      performance, and physical function increased significantly. Muscle fiber
      composition was changed by a relative decrease in type 2x muscle fiber number
      whereas muscle size at the fiber level was unchanged. There were no effects of
      combining the training with protein intake. CONCLUSIONS: High-load strength
      training is associated with improvements in muscle strength and power, physical
      performance, and quality of life. The effects were surprisingly not associated
      with muscle hypertrophy, and the results did not reveal any additional benefit of
      combining the training with protein intake. The positive results in muscle
      strength and physical performance have clinically relevant implications in the
      treatment of patients undergoing dialysis.

PMID- 22959783
TI  - Atypical chest pain--it's time to be rid of it.

PMID- 22959781
TI  - A pilot study of active vitamin D administration and insulin resistance in
      African American patients undergoing chronic hemodialysis.
AB  - OBJECTIVE: Insulin resistance (IR) is associated with increased cardiovascular
      risk in multiple patient populations, including those undergoing chronic
      hemodialysis (CHD). Active vitamin D deficiency has been proposed to play a role
      in the extent of IR observed in patients with CHD. We postulated that
      administration of paracalcitol, an active vitamin D medication, influences IR in
      patients with CHD. DESIGN AND METHODS: This was a pilot randomized controlled
      trial. Ten prevalent CHD patients receiving a stable dose of paracalcitol were
      recruited. Paracalcitol was withheld for 8 weeks in all patients (phase I).
      Parathyroid hormone levels were managed with the calcium-sensing receptor agonist
      cinacalcet. At week 8, patients were randomized to continue cinacalcet or to
      restart paracalcitol for 8 weeks (phase II). The primary outcome was the change
      in IR measured by the glucose disposal rate (GDR) using hyperinsulinemic
      euglycemic clamp (HEGC) method. Secondary outcomes included changes in IR between
      groups in indirect indices of IR, biomarkers of inflammation, and adipokine
      levels. RESULTS: The mean age was 49 years (range, 46-57 years) and 40% of
      patients were women. There was no detectable change in the GDR at the end of
      phase I (P = .7) when compared with baseline values. There was also no
      statistically significant difference in GDR between groups at the end of phase II
      (P = .9). No changes were observed in indirect indices of IR, adipokine levels,
      or biomarkers of inflammation in either phase. CONCLUSION: The results of this
      pilot study suggest that withdrawal of paracalcitol over 8 to 16 weeks and
      replacement for 8 weeks after withdrawal does not influence IR measured by HEGC
      in patients receiving CHD.

PMID- 22959784
TI  - Tombstone ST elevations: ... not necessarily a harbinger of doom!

PMID- 22959786
TI  - Portable monitoring for obstructive sleep apnea: the horse is out of the barn
      avoiding pitfalls.

PMID- 22959785
TI  - Coronary artery disease is under-diagnosed and under-treated in advanced lung
      disease.
AB  - BACKGROUND: Coronary artery disease is a potentially treatable comorbidity
      observed frequently in both chronic obstructive pulmonary disease and
      interstitial lung disease. The prevalence of angiographically proven coronary
      artery disease in advanced lung disease is not well described. We sought to
      characterize the treatment patterns of coronary artery disease complicating
      advanced lung disease and to describe the frequency of occult coronary artery
      disease in this population. METHODS: We performed a 2-center, retrospective cross
      sectional study of patients with either chronic obstructive pulmonary disease or
      interstitial lung disease evaluated for lung transplantation. Medications and
      diagnoses before the transplant evaluation were recorded in conjunction with left
      heart catheterization results. RESULTS: Of 473 subjects, 351 had chronic
      obstructive pulmonary disease, and 122 had interstitial lung disease. In subjects
      diagnosed clinically with coronary artery disease, medical regimens included a
      statin in 78%, antiplatelet therapy in 62%, angiotensin-converting enzyme
      inhibitor or angiotensin receptor blocker in 42%, and a beta-blocker in 37%. Ten
      percent were on no medication from these 4 classes. Fifty-seven percent of these
      subjects were on an antiplatelet agent as well as a statin, and 13% were on
      neither. Beta-blockers were less frequently prescribed in chronic obstructive
      pulmonary disease than interstitial lung disease (23% vs 58%, P=.007). Coronary
      angiography was available in 322 subjects. It demonstrated coronary artery
      disease in 60% of subjects, and severe coronary artery disease in 16%. Occult
      coronary artery disease and severe occult coronary artery disease were found in
      53% and 9%, respectively. There were no significant differences in angiographic
      results between chronic obstructive pulmonary disease and interstitial lung
      disease, despite imbalanced risk factors. CONCLUSIONS: Coronary artery disease is
      common in patients with advanced lung disease attributable to chronic obstructive
      pulmonary disease or interstitial lung disease and is under-diagnosed. Guideline
      recommended cardioprotective medications are suboptimally utilized in this
      population.

PMID- 22959787
TI  - The shifting of the torsion axis of the foot during the stance phase of lateral
      cutting movements.
AB  - Previously, foot torsion has been studied with respect to peak angles during
      athletic movements. Athletic footwear often contains a torsion element that
      dictates a torsion axis of the shoe. The location of the axis of rotation of the
      foot is, however, unknown. Therefore, the purpose of this study was to describe
      the torsion axis location during the stance phase of lateral cutting movements.
      Thirty-nine subjects performed a barefoot lateral jab and 19 subjects performed a
      barefoot shuffle cut. Markers were placed on the fore- and rearfoot and their
      movement was quantified using a 3-D video system. The torsion axis location was
      determined using a modified finite helical axis approach during the stance phase
      while the torsion angle was calculated as the amount of rotation around the
      torsion axis. At the beginning of the stance phase, the axis was located on the
      medial aspect of the foot. During the stance phase, the axis shifted towards the
      lateral side of the foot before the axis moved back to the medial aspect of the
      foot at the end of stance. For both movements significant correlations between
      the axis location in the vertical and medio-lateral directions and the torsion
      angle were found. With larger torsion (forefoot inversion) angles the axis was in
      a more lateral and plantar location within the foot. With this knowledge, a shoe
      torsion system where the shoe torsion axis location is in agreement with the foot
      axis location could be developed.

PMID- 22959788
TI  - Two-part fractures of the proximal humerus.
AB  - Between 1981 and 1991, 137 patients had 141 two-part proximal humerus fractures.
      One hundred thirteen surgical neck, 24 greater tuberosity, 2 anatomic neck, and 2
      lesser tuberosity fractures were studied. Eleven patients had died in the
      interim; the remaining cases were reviewed. The mean age of patients with
      surgical neck fractures was 57 years (range 20 to 91 years), and 62.8% (71 cases)
      were women. In 38% of cases there was another significant medical problem. Eighty
      (70.8%) cases were treated with a sling and early isometric and pendulum
      exercises. Bony union was obtained in an average of 3.2 months (range 2 to 8
      months), and 87.5% achieved satisfactory function. The mean age of patients with
      greater tuberosity fractures was 37 years (range 20 to 59 years), and 79.2% (19
      cases) were men. Ten (41.7%) cases were treated with open reduction and internal
      fixation, and the remainder were treated without surgery. All patients improved
      to a satisfactory level of function. Anatomic neck fractures (two) were treated
      with surgery. Lesser tuberosity fractures (two) were treated conservatively and
      had good functional results. It appears that conservative measures when coupled
      with early isometric and pendulum exercises produce a satisfactory result in
      surgical neck fractures. Similarly, conservative treatment for nondisplaced
      greater tuberosity fractures and operative intervention for displaced fractures
      resulted in satisfactory function. Lesser tuberosity fractures without limitation
      of motion appear to do well with a sling and early motion.

PMID- 22959789
TI  - Reduction of traumatic, primary anterior shoulder dislocations with local
      anesthesia.
AB  - This study evaluates the use of local anesthesia in the reduction of acute
      shoulder dislocations. Patients with a primary traumatic dislocation of the
      shoulder were randomly assigned to receive either local anesthesia or intravenous
      anesthesia. The patients were observed for any complication during and after the
      procedure, and the methods used were evaluated with a visual analog scale. In the
      period from November 1991 to September 1993, 81 patients were admitted to our
      departments, and 68 patients were included in the study. Average age was 48 years
      (range 15 to 79 years); 29 men and 39 women were studied. Thirty-five patients
      were randomly assigned to receive intravenous anesthesia; 33 had a successful
      reduction, and two had a failed reduction. Thirty-three patients received local
      anesthesia; 32 had a successful reduction, and one had a failed reduction. Ten
      patients treated with the intravenous method had respiratory depression, and six
      required an antidote. No systemic or local side effects and no neurovasculor
      injuries were recorded. We did not observe any superficial or deep infection in
      the local anesthetic group. No statistical difference was found between the
      average visual analog value scale in the two groups. Local anesthesia to reduce
      acute primary anterior dislocation of the shoulder is a simple and safe method.

PMID- 22959790
TI  - Cost of shoulder surgery.
AB  - A cost analysis of four common shoulder procedures was performed to better advise
      patients and payers of the expected costs and to provide a foundation for future
      cost/benefit analysis. Four groups of 50 patients each were evaluated. Group 1
      underwent primary, open rotator cuff repair. Group 2 underwent open, anterior
      instability repair. Group 3 underwent arthroscopic subacromial decompression.
      Group 4 underwent hemiarthroplasty or total shoulder arthroplasty. The surgical
      and anesthetic fees, hospital bills, and perioperotive consultation charges were
      obtained and tabulated for all patients. The average ages for groups 1 to 4 were
      56, 32, 50 and 63 years, respectively. In group 1 37% of the patients had
      worker's compensation, 35% had private insurance, and 28% had Medicare. In group
      2 64% of the patients had worker's compensation, and 36% had private insurance.
      In group 3 39% of the patients had worker's compensation, 48% had private
      insurance, and 13% had Medicare. In group 4 4% of the patients had worker's
      compensation, 43% had private insurance, and 53% had Medicare. For group 1 the
      average length of stay was 3 days, and the average total cost was $9444. For
      group 2 the average stay was 1.7 days, and the average cost was $8675. For group
      3 the average stay was 0 days, and the average cost was $7246. For group 4 the
      average stay was 5 days, and the average cost was $16,323. We believe that these
      figures represent the direct costs of four common types of shoulder surgery in a
      private setting and that such data are important to decision-making in a changing
      health care environment.

PMID- 22959791
TI  - Total shoulder arthroplasty: Some considerations related to glenoid surface
      contact.
AB  - The area of prosthetic surface contact is an important surgeon-controlled
      variable in total shoulder arthroplasty and is related to the geometry of the
      glenoid and humeral articular surfaces and their relative positions. This study
      explores some of the factors that affect joint surface contact area. We measured
      the humeral and the glenoid articular surface angles in the superior-inferior and
      anteroposterior planes for two prosthesis systems representative of those in
      common clinical use. On the basis of these data we determined the range of
      glenohumeral positions providing full glenoid surface contact, a condition in
      which all of the articular surface of the glenoid component is in contact with
      the articular surface of the humeral component. We found a wide variability in
      the range of glenohumeral positions providing full glenoid contact with different
      prosthetic combinations. Some combinations do not even offer full glenoid surface
      contact with the joint in the centered position, for example, when the center of
      the humeral head articular surface is opposed to the center of the glenoid
      articular surface. The maximal range of glenohumeral positions providing full
      glenoid surface contact was 117 degrees  for a combination with a small radius of
      head curvature and a large articular surface angle. The relative positions of the
      humeral and glenoid articular surfaces also have a major influence on the joint
      contact area. Some combinations offer full glenoid surface contact only in a
      position of humeral abduction with respect to the scapula. Loss of full glenoid
      surface contact between the glenoid and humerus may allow for unwanted
      translations of the humeral head on the glenoid in the direction where contact is
      lacking. Furthermore, in positions where full surface contact is lacking, humeral
      bone or soft tissue may make unwanted contact with the glenoid. These results
      suggest that the design of the humeral articular surface and the surgical
      procedure should maximize full glenoid surface contact in functionally important
      positions.

PMID- 22959792
TI  - Resection arthrodesis of the shoulder with autogenous fibular bone grafts.
AB  - We report the results of wide local excision of stage II8 proximal humeral tumors
      followed by reconstruction with parallel nonvascularized fibular bone grafts in
      three patients. Mean follow-up was 5 years (range 3 years to 8 years, 6 months).
      The pathologic diagnosis was osteogenic sarcoma in two patients and Ewing's
      sarcoma in one. The rotator cuff and deltoid were excised to achieve a wide
      margin around these tumors. All patients remain free from disease. They were able
      to return to previous work and sport activities. Two had a fracture of the graft;
      one fell from a mountain bike and the other fell at work. The former fracture
      united; the latter fracture required fixation and bone grafting to achieve union.
      By Enneking's 30-point functional evaluation, all three patients were in the
      excellent category with scores of 25, 26, and 28. We conclude that for the
      treatment of malignant tumors of the shoulder region with muscle involvement,
      excision followed by arthrodesis with parallel autogenous fibular bone grafts
      provides a method of retaining satisfactory upper limb function and acceptable
      cosmesis.

PMID- 22959793
TI  - Contribution of passive bulk tissues and deltoid to static inferior glenohumeral
      stability.
AB  - The relative stabilizing effect of the passive bulk tissues and deltoid to
      inferior humeral displacement was studied. The humeral head center relative to
      the glenoid center was determined by a magnetic tracking device in 10 shoulder
      specimens for the bulk tissue study and in 13 for the deltoid study. Twelve
      static recordings were obtained per specimen: (1) with and without a 1.5 kg load,
      (2) with the humerus adducted hanging freely and abducted 90 degrees  in neutral
      rotation, and (3) in three stages of dissection: with all tissues intact, after
      removal of the tissues superficial to the deltoid, and after removal of the
      deltoid. In both humeral adduction and abduction, the passive bulk tissues and
      deltoid did not provide significant stability to the shoulder joint.

PMID- 22959794
TI  - Neglected intraarticular entrapment of the medial epicondyle after dislocation of
      the elbow.

PMID- 22959795
TI  - Preoperative, intraoperative, and immediate postoperative skeletal scintigraphy
      to locate and facilitate excision of an osteoid osteoma of the coronoid process.
AB  - We report the case of a 39-year-old woman with a 3-year history of inflammatory
      right elbow pain caused by an osteoid osteoma. Two hours before the operation,
      the patient received an intravenous injection of 350 MBq of Tc 99m
      dimethylaminodiphosphonate. The resection of the nidus, guided by the
      intraoperative scintigraphy, was easily performed and confirmed by postresection
      counting and an x-ray film. Three hours after the operation, new scintigraphic
      views without further injection of the bone-seeking radioisotope confirmed the
      complete removal of the nidus. When immediate postoperative scintigraphy shows
      the disappearance of the focal reinforcement of activity, it gives additional
      evidence of complete tumor resection.

PMID- 22959796
TI  - Strength testing of the shoulder.

PMID- 22959797
TI  - Patient diary helps assessment.

PMID- 22959798
TI  - Photodynamic therapy for unresectable cholangiocarcinoma: a comparative
      effectiveness systematic review and meta-analyses.
AB  - BACKGROUND: Photodynamic therapy (PDT) with placement of a biliary stent may
      improve bile duct patency in patients with cholangiocarcinoma (CCA). We aimed to
      determine the effectiveness of biliary stenting with PDT compared to biliary
      stenting alone in the palliative treatment of CCA. MATERIALS AND METHODS: Several
      databases were searched from inception to December 2011 for prospective studies
      comparing biliary stenting with PDT vs. biliary stenting only for CCA. Outcomes
      of interest included patient survival, quality of life (using Karnofsky score),
      and serum bilirubin levels. The relative risk (RR) for dichotomous outcomes and
      the weighted mean difference (WMD) for continuous outcomes were estimated using
      DerSimonian and Laird random-effects model. Inconsistency was quantified using
      I(2) statistics. The extent of publication bias was ascertained by visual
      inspection of funnel plots and Egger's test. RESULTS: There were six studies that
      met inclusion criteria. A total of 170 participants received PDT and 157 had
      biliary stenting only. Compared with biliary stenting, PDT was associated with a
      statistically significant increase in the length of survival (WMD 265 days; 95%
      CI: 154-376; p = 0.01; I(2) = 65%), improvement in Karnofsky scores (WMD 7.74;
      95% CI: 3.73-11.76; p = 0.01; I(2)= 14%), and a trend for decline in serum
      bilirubin (WMD -2.92 mg/dL; 95% CI: -7.54 to 1.71; p=0.22; I(2) = 94%). The
      pooled event rate for biliary sepsis was 15% and was similar between PDT and
      control groups. CONCLUSION: Palliative treatment of CCA with PDT is associated
      with increased survival benefit, improved biliary drainage, and quality of life.
      However, the quality of this evidence is low.

PMID- 22959799
TI  - A basic study on hypericin-PDT in vitro.
AB  - The effect of photo dynamic therapy (PDT) using hypericin as a photosensitiser
      and the effect of PDT on intracellular ATP levels using different lamps in a
      human leukemic monocyte lymphoma cell line (U937) were studied. The time required
      for hypericin to penetrate into the cancer cells was 1h, and incubation for more
      than 3h post-irradiation with hypericin-PDT was required to observe effects.
      Thus, if cancer cell death does not occur immediately following irradiation, it
      is unnecessary to perform additional irradiation, as most of the cells die via
      apoptosis during the incubation period post-irradiation. When hypericin-PDT was
      performed using a Na-Li lamp as a light source, the cell viability decreased
      approximately 55% immediately following irradiation for 5 min; however, after a 5
      h post-irradiation incubation, the cell viability approached 0%. Concurrently,
      intracellular ATP levels increased markedly; thus, irradiation (0.225 J/cm(2))
      for 5 min provided the best results in terms of the highest degree of cancer cell
      apoptosis. Similar experiments were performed using three different LED lamps
      respectively. When cells were treated with the LED lamps, with maximum peaks of
      599 nm and 595 nm, the cell viability approached 0% after incubation for 5h
      following 15 min of irradiation (0.04 J/cm(2) and 0.099 J/cm(2), respectively).
      We confirmed that incubating the cells for more than 3h in a 100 * diluted
      hypericin solution was the most effective for PDT and that a LED lamp of low
      light intensity led to the highest apoptosis rate in the U937 cells.

PMID- 22959800
TI  - Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC)
      transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of
      gastric cancer cells in vitro.
AB  - BACKGROUND: Recently, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT)
      is being widely used in cancer therapy owing to the tumor-specific accumulation
      of photosensitizing protoporphyrin IX (PpIX) after the administration of ALA. In
      the present study, by focusing on genes involved in the porphyrin biosynthesis
      pathway, we aimed to explore biomarkers that are predictive for the efficacy of
      ALA-PDT. METHODS: We used five lines of human gastric cancer cells to measure the
      ALA-based photocytotoxicity. ALA-induced production of PpIX in cancer cells was
      quantified by fluorescence spectrophotometry. To examine the potential
      involvement of PEPT1 and ABCG2 in the ALA-PDT sensitivity, stable cell lines
      overexpressing PEPT1 were established and ABCG2-specific siRNA used. RESULTS: We
      observed that three cell lines were photosensitive, whereas the other two cell
      lines were resistant to ALA-based photocytotoxicity. The ALA-based
      photocytotoxicity was found to be well correlated with intracellular PpIX levels,
      which suggests that certain enzymes and/or transporters involved in ALA-induced
      PpIX production are critical determinants. We found that high expression of the
      peptide transporter PEPT1 (ALA influx transporter) and low expression of the ATP
      binding cassette transporter ABCG2 (porphyrin efflux transporter) determined ALA
      induced PpIX production and cellular photosensitivity in vitro. CONCLUSION: PEPT1
      and ABCG2 are key players in regulating intracellular PpIX levels and determining
      the efficacy of ALA-based photocytotoxicity against gastric cancer cells in
      vitro. Evaluation of the expression levels of PEPT1 and ABCG2 genes could be
      useful to predict the efficacy of ALA-PDT. Primers specific to those target genes
      are practical and useful biomarkers for predicting the photo-sensitivity to ALA
      PDT.

PMID- 22959801
TI  - Investigating the efficiency of novel metallo-phthalocyanine PDT-induced cell
      death in MCF-7 breast cancer cells.
AB  - BACKGROUND: Cancer cells possess an innate resistance to inducers of the death
      program. Novel phthalocyanines with improved physiochemical properties harbor the
      potential for use in photodynamic therapy (PDT); a rising treatment alternative
      preferred for its mostly asymptomatic application and unique mechanism of action.
      METHODS: This study aimed to determine whether in vitro PDT with two new metallo
      phthalocyanines (metallo-Pcs), AlPcSmix and GePcSmix, are similarly effective in
      overcoming resistance to cell death in MCF-7 cells with a brief comparison to an
      established chemotherapeutic agent, etoposide. Optimum induction of cell death in
      these cancer cells was initially determined via measurement of cellular
      respiration and energy production levels. Indications of cytotoxicity and cell
      stress were evaluated and resultant levels compared to those in cells treated
      with etoposide. RESULTS: Initial findings report AlPcSmix is predominantly more
      detrimental to cellular function and homeostasis when excited via red light
      irradiation of 15 J/cm(2). It appears GePcSmix requires higher dosage
      administrations to achieve similar responses within identical populations.
      However, due to the mechanism of PDT application, our findings indicate a greater
      toxic effect with both phthalocyanines when compared to etoposide of higher
      dosage within MCF-7 cells. CONCLUSION: Both phthalocyanines, despite similarity
      in structure, indicate induction of different cell death response pathways based
      on their toxicity potential. These therefore show great promise as potential PDT
      agents for the treatment of cancer.

PMID- 22959802
TI  - Cutaneous penetration of the topically applied photosensitizer Pc 4 as detected
      by intravital 2-photon laser scanning microscopy.
AB  - The fundamental mechanism of photodynamic therapy (PDT)-induced cell death has
      been characterized, but early critical PDT events in vivo remain incompletely
      defined. With the recent development in advanced fluorescence imaging modalities,
      such as intravital 2-photon laser scanning microscopy (2P-LSM), researchers are
      now able to investigate and visualize biological processes with high resolution
      in real time. This powerful imaging technology allows deep tissue visualization
      with single-cell resolution, thus providing dynamic information on the 3
      dimensional architectural makeup of the tissue. The main goal of this study was
      to determine the cutaneous penetration of a topically applied photosensitizer,
      the silicon phthalocyanine Pc 4, into the skin of live animals and to assess the
      effective absorption of Pc 4 through the skin barrier. Our 2P-LSM images indicate
      that Pc 4 penetrates to the epidermal/dermal junction of mouse skin. The data
      also indicate that the degree of Pc 4 absorption is dose dependent. These
      findings represent initial steps that may help in improving the clinical
      utilization of topical Pc 4-PDT.

PMID- 22959803
TI  - Optical properties of hematoporphyrin monomethyl ether (HMME), a PDT
      photosensitizer.
AB  - We report on some of the optical properties of Hemoporfin (hematoporphyrin
      monomethyl ether, HMME), a photodynamic therapy (PDT) photosensitizer that has
      been in clinical trials in China since the early 1990s. We characterized the
      photosensitizer on the basis of one- and two-photon absorption and fluorescence
      emission. The effects of photobleaching were probed to characterize its decay
      kinetics. Additionally, we determined time resolved fluorescence and thermal
      effects on fluorescence and absorption properties.

PMID- 22959804
TI  - Modulation of telomerase and signal transduction proteins by hexyl-ALA
      photodynamic therapy (PDT) in human doxorubicin resistant cancer cell models.
AB  - AIMS: This study employed a doxorubicin resistant (MES-SA-Dx5) human uterine
      sarcoma cell line and its counterpart (MES-SA), to elucidate the efficacy of
      aminolevulinic acid-hexylester (hexyl-ALA) mediated PDT at molecular and
      transcriptional levels. METHODS: Hexyl-ALA generated protoporphyrin IX in both
      cells were determined by molecular probes using Confocal Laser Scanning
      Microscopy. The hexyl-ALA-PDT induced signal transduction proteins and mode of
      cell death were quantitated by CASE ELISA assays and DAPI staining. The
      modulation of hTERT mRNA expression and telomerase activity were investigated by
      TaqMan real-time PCR and ELISA respectively. Hexyl-ALA-PDT mediated cell
      migratory effect was determined by wound-healing assay. RESULTS: The results
      demonstrated that mitochondria were the major target of hexyl-ALA. At LD(30),
      hexyl-ALA-PDT significantly provoked an up-regulation of phosphorylated p38MAPK
      and JNK proteins in both cells. Hexyl-ALA-PDT down-regulated hTERT (a catalytic
      subunit of telomerase) mRNA expression and showed a strong correlation with
      diminished telomerase activity in both cells (MES-SA: r(2) = 0.9932; MES-SA-Dx5:
      r(2) = 0.9775). The suppression of cell migratory effect in both cells was
      obtained after hexyl-ALA-PDT. Further, 50% and 30% of apoptotic cells were
      attained at LD(50), for wild-type and drug resistant cells respectively. Unlike
      the wild-type, a higher PDT dose was crucial to induce apoptosis in the drug
      resistant cells. CONCLUSIONS: Our study provides the first evidence that p38MAPK
      and JNK kinases played a vital role in triggering hexyl-ALA-PDT-induced
      apoptosis, down-regulated hTERT mRNA expression and telomerase activity in both
      proposed cells. In vivo studies are worth examining for the benefit of clinical
      applications in drug resistant cancers and PDT development.

PMID- 22959805
TI  - Hyaluronic acid-functionalized mesoporous silica nanoparticles for efficient
      photodynamic therapy of cancer cells.
AB  - Mesoporous silica nanoparticles (MSN) for photodynamic therapy (PDT) were coated
      with poly-(L-lysine) and hyaluronic acid (HA) by using the layer-by-layer method.
      HA is able to target cancer cells over-expressing the corresponding CD44
      receptor. MSN functionalized with HA (MSN-HA) were more efficient than MSN
      without the targeting moiety when PDT was performed at low fluence (14 Jcm(-2))
      and low dosage of MSN (20 MUgmL(-1)) on HCT 116 colorectal cancer cells, known to
      over-express the CD44 receptor. Incubation of HCT-116 cancer cells with an excess
      of HA impaired the PDT effect with MSN-HA thus demonstrating that an active
      endocytosis mechanism was involved in the uptake of MSN-HA by these cells.

PMID- 22959806
TI  - Photodynamic therapy in urology: what can we do now and where are we heading?
AB  - BACKGROUND: Photodynamic therapy (PDT) is an innovative technique in oncologic
      urology. Its application appears increasingly realistic to all kind of cancers
      with technological progress made in treatment planning and light delivery
      associated with the emergence of novel photosensitizers. The aim of this study is
      to review applications of this technique in urology. MATERIALS AND METHODS: We
      reviewed the literature on PDT for urological malignancies with the following key
      words: photodynamic therapy, prostate cancer, kidney cancer, urothelial cancer,
      penile cancer and then by cross-referencing from previously identified studies.
      RESULTS: Focal therapy of prostate cancer is an application of PDT. Clinical
      studies are ongoing to determine PDT efficacy and safety. PDT as salvage
      treatment after radiotherapy has been tested. Oncologic results were promising
      but important side effects were reported. Individual dosimetric planning is
      necessary to avoid toxicity. PDT was tested to treat superficial bladder
      carcinoma with promising oncologic results. Serious side effects have limited use
      of first photosensitizers generation. Second generation of photosensitizer
      allowed reducing morbidity. For upper urinary tract carcinoma and urethra, data
      are limited. Few studies described PDT application in penile oncology for
      conservative management of carcinoma in situ and premalignant lesions. For renal
      cancer, PDT was only tested on preclinical model despite of its potential
      application. No data is available concerning PDT application for testicular
      cancer. CONCLUSION: PDT clinical applications in urology have proved a kind of
      efficiency balanced with an important morbidity. Development of new
      photosensitizer generations and improvement in illumination protocols should
      permit to decrease side effects.

PMID- 22959807
TI  - Temoporfin mediated photodynamic therapy in patients with local persistent and
      recurrent nasopharyngeal carcinoma after curative radiotherapy: a feasibility
      study.
AB  - BACKGROUND: The treatment of persistent and recurrent nasopharyngeal carcinoma
      (NPC) remains a challenge, especially in Indonesia. We investigated the safety
      and efficacy of temoporfin mediated photodynamic therapy (PDT) for patients with
      local persistent and recurrent NPC. MATERIAL AND METHODS: Twenty-two patients
      with persistent and recurrent NPC (maximum tumor depth < 10mm) underwent PDT
      under local anesthesia with use of a nasopharyngeal light applicator. Three
      different drug doses and light intervals have been administered: treatment arm A:
      0.15 mg/kg Foscan; 96 h drug-light interval; B: drug dose of 0.10 mg/, 48 h drug
      light interval; C: drug dose of 0.075 mg/kg, 24 h drug-light interval. Toxicity
      was measured by using the CTCAE 3.1 scale. RESULTS: Arm A consisted of eight
      patients, arms B and C consisted of seven patients. The treatment procedure was
      well tolerable under local anesthesia. The most common grade III toxicities for
      all groups is headache (n = 7; 33%). No grade IV toxicity was seen. One patient
      died 2 days after treatment due to a misdiagnosed pneumonia. In 17 of the 22
      patients a biopsy was performed after 40 weeks and showed no tumor in all
      biopsies. Arm A seems, in addition to comparable toxicity, clinically more
      effective than arms B and C. CONCLUSION: The present study demonstrated that
      temoporfin mediated photodynamic therapy is a relatively simple technique that
      can be utilized to treat residual or recurrent nasopharyngeal cancer, restricted
      locally to the nasopharynx.

PMID- 22959808
TI  - Kimura's Disease-Revisited.

PMID- 22959811
TI  - Life cycle, host range and temporal variation of Ophiocordyceps
      unilateralis/Hirsutella formicarum on Formicine ants.
AB  - Ophiocordyceps unilateralis sensu lato infects ants, modifies their behavior, and
      is found in many countries around the world. One unifying concept of all such
      parasitic associations is that both the parasite and the host adapt to maximize
      their fitness and reproductive output. However, little is known about the
      reproductive life span of this pathogen or about its alternation between asexual
      and sexual states, even though these two states affect host population dynamics
      differently. To address these issues, a permanent plot in a tropical rainforest
      was surveyed over the course of two years to examine the development of O.
      unilateralis s.l. and the incidence of infection of Polyrhachis and Camponotus
      ants, which were found to be specifically attacked by this fungus in Thailand. We
      document here for the first time the life cycle of this pathogen over the long
      term, which provides fundamental knowledge for the understanding of this
      fascinating host-parasite interaction.

PMID- 22959812
TI  - Neural correlates of hot and cold executive functions in polysubstance addiction:
      association between neuropsychological performance and resting brain metabolism
      as measured by positron emission tomography.
AB  - The study of substance-abuse-related neuropsychological deficits and brain
      alterations may provide a better understanding of the neuroadaptations associated
      with addiction. In this study we investigated the association between performance
      on neuropsychological tests of cold and hot executive functions and regional
      brain metabolism. Measured with positron emission tomography (PET), in a sample
      of 49 substance-dependent individuals (SDI). Neuropsychological performance in
      the SDI group was compared to that of a non-drug-using control group of 30
      participants, and associated with two sets of PET-derived dependent measures: one
      based on regions of interest (examining mean uptake in selected regions), and a
      second based on voxel uptake measures (using Statistical Parametric Mapping voxel
      based whole-brain analyses). Behavioral analyses showed that SDI had poorer
      performance than controls across executive function and emotion processing
      measures. Regression models showed that SDI's performance in "cold" executive
      tests (i.e., updating, inhibition and flexibility) was associated with regional
      metabolism in the dorsolateral prefrontal cortex (DLPFC), mid-superior frontal
      gyrus, superior and inferior temporal gyrus and inferior parietal cortex, whereas
      performance in "hot" executive functions (i.e., self-regulation, decision-making
      and emotion perception) was associated with DLPFC, mid-superior frontal gyrus,
      anterior and mid-posterior cingulate, and temporal and fusiform gyrus. These
      results are discussed in terms of their relevance for the understanding of
      cognitive dysfunction and neuroadaptations linked to addiction.

PMID- 22959813
TI  - Functional and structural neural indices of risk aversion in obsessive-compulsive
      disorder (OCD).
AB  - Obsessive-compulsive disorder (OCD) patients suffer from risk aversion, which may
      be mediated by their exaggerated response to threat and diminished response to
      reward. In this study, 13 OCD patients and 13 healthy matched controls underwent
      functional magnetic resonance imaging (fMRI) while playing an interactive risky
      choice game encompassing distinct intervals of threat and reward; as well as
      anatomical diffusion tensor imaging (DTI). Compared to healthy controls OCD
      patients were reluctant to make risky choices during the game. Furthermore, they
      displayed higher amygdala activation to threat; lower nucleus accumbens (Nacc)
      activation to reward and reduced functional connectivity of the amygdala and Nacc
      to two frontal regions, the orbito-frontal cortex (OFC) and the dorsal anterior
      cingulate cortex (dACC), respectively. OCD patients also displayed reduced
      structural integrity in clusters within the uncinate and cingulum fiber tracts.
      Finally, these deficits in limbic-frontal connectivity pathways, both at the
      functional and structural level, were associated with severity of OCD symptoms,
      as well as with each other. Our results thus suggest that risk aversion in OCD is
      mediated by abnormal limbic responses to threatening and rewarding stimuli, as
      well as by deficient functional and structural limbic-frontal connectivity. Such
      deficiency characterization may aid in identifying neural predictors for
      treatment response and localizing individual targets for direct neural
      intervention treatments.

PMID- 22959814
TI  - Association of microstructural white matter abnormalities with cognitive
      dysfunction in geriatric patients with major depression.
AB  - Major depression disorder (MDD) is one of the most common causes of disability in
      people over 60years of age. Previous studies have linked affective and cognitive
      symptoms of MDD to white matter (WM) disruption in limbic-cortical circuits.
      However, the relationship between clinical cognitive deficits and loss of
      integrity in particular WM tracts is poorly understood. Fractional anisotropy
      (FA) as a measure of WM integrity was investigated in 17 elderly MDD subjects in
      comparison with 18 age-matched controls using tract-based spatial statistics
      (TBSS) and correlated with clinical and cognitive parameters. MDD patients
      revealed significantly reduced FA in the right posterior cingulate cluster (PCC)
      compared with controls. FA in the right PCC (but not in the left PCC) showed a
      significant positive correlation with performance in a verbal naming task, and
      showed a non-significant trend toward a correlation with verbal fluency and
      episodic memory performance. In control subjects, no correlations were found
      between cognitive tasks and FA values either in the right or left PCC. Results
      provide additional evidence supporting the neuronal disconnection hypothesis in
      MDD and suggest that cognitive deficits are related to the loss of integrity in
      WM tracts associated with the disorder.

PMID- 22959815
TI  - Effect of the muscle coactivation during quiet standing on dynamic postural
      control in older adults.
AB  - Recently, several studies have reported that muscle coactivation during static
      postural control increases with aging. Although greater muscle coactivation
      during quiet standing enhances joint stability, it may reduce dynamic postural
      control. The purpose of this study was to investigate the effect of muscle
      coactivation during quiet standing on dynamic postural control. Seventy older
      adults (81.1 +/- 7.2 years) participated in this study. Static postural control
      was evaluated by postural sway during quiet standing, whereas dynamic postural
      control was evaluated by the functional reach and functional stability boundary
      tests. Electromyography of the soleus (SOL) and tibialis anterior (TA) was
      recorded during quiet standing, then coactivation was evaluated using the co
      contraction index (CI). We used multiple regression analysis to identify the
      effect of muscle coactivation during standing on each dynamic postural control
      variable using age, body mass index (BMI), gender, timed up and go (TUG) tests,
      postural sway area and CI during quiet standing as independent variables. TUG
      tests were added to the model to evaluate the effect of functional mobility on
      dynamic postural control with a fixed base. The multiple regression analysis
      revealed that CI during standing was significantly related to all of the dynamic
      postural control tasks. The functional reach distance was significantly
      associated with CI during standing, age and TUG (p<0.05). The functional
      stability boundary for forward and backward were associated only with CI during
      standing (p<0.05). This study revealed that muscle coactivation during quiet
      standing is independently associated with dynamic postural control abilities.

PMID- 22959817
TI  - Human metapneumovirus in Jordan: prevalence and clinical symptoms in hospitalized
      pediatric patients and molecular virus characterization.
AB  - Respiratory viral infections account for significant morbidity and mortality
      especially in young children worldwide. Human metapneumovirus (hMPV) causes
      illnesses ranging from mild respiratory problems to bronchiolitis and severe
      pneumonia. From January to December 2007, 220 nasopharyngeal aspirates were
      collected from children younger <= 13 years old hospitalized with lower
      respiratory tract infection to detect hMPV by revese transcription-polymerase
      chain reaction and to clone and sequence the hMPV-positive samples. Human
      metapneumovirus was detected in 28 (12.7%) specimens with a median age of 7
      months (range 1.3 to 24 months). Human metapneumovirus type A and type B were
      detected in 26 (93%) and 8 (28.6%) of specimens, respectively. Coinfection with
      hMPV type A and type B was detected in 6 (21.4%) specimens positive for hMPV. The
      major clinical diagnosis of hMPV-positive patients was bronchiolitis (75%). Human
      metapneumovirus and hMPV type B were found to be significantly associated with
      bronchiolitis (P = 0.03 and 0.01, respectively). Human metapneumovirus and hMPV
      type A were found to be significantly associated with pneumonia (P = 0.004 and
      0.002, respectively). The main symptoms in patients infected with hMPV were cough
      (92.9%), fever (82.1%), and wheezing (78.6%), with a significant association of
      hMPV type A with fever (P = 0.018). Human metapneumovirus was seasonally
      distributed; most infections with hMPV were reported in the late winter and early
      spring. The peak of hMPV incidence was in February (10/28; 35.7%). Sequencing of
      purified plasmid DNA was performed in forward and reverse direction to confirm
      the results of hMPV-positive samples which scored 97% identity to hMPV type A
      genome isolate NL/17/00 and showing C-T variation that had no effect on the amino
      acid sequence F(Phe)-F(Phe).

PMID- 22959818
TI  - Genetic features and molecular epidemiology of Enterococcus faecium isolated in
      two university hospitals in Brazil.
AB  - The global emergence of vancomycin-resistant Enterococcus faecium (VREfm) has
      been characterized by a clonal spread of strains belonging to clonal complex 17
      (CC17). Genetic features and clonal relationships of 53 VREfm isolated from
      patients in 2 hospitals in Ribeirao Preto, Sao Paulo, Brazil, during 2005-2010
      were determined as a contribution to the Brazilian evolutionary history of these
      nosocomial pathogens. All isolates were daptomycin susceptible, vancomycin
      resistant, and had the vanA gene. The predominant virulence genes were acm and
      esp. Only 5 VREfm isolated in 2005-2006 had intact Tn1546, while 81% showed
      Tn1546 with deleted left extremity and insertion of IS1251 between the vanS and
      vanH genes. Multilocus sequence typing analysis permitted the identification of 9
      different sequence types (STs), with 5 being new ones (656, 657, 658, 659, and
      660). Predominant STs were ST412 and ST478, all belonging to CC17, except ST658.
      This is the first report of the ST78 in Brazil.

PMID- 22959819
TI  - Confirmation of a late middle Pleistocene age for the Omo Kibish 1 cranium by
      direct uranium-series dating.
AB  - While it is generally accepted that modern humans evolved in Africa, the specific
      physical evidence for that origin remains disputed. The modern-looking Omo 1
      skeleton, discovered in the Kibish region of Ethiopia in 1967, was
      controversially dated at ~130 ka (thousands of years ago) by U-series dating on
      associated Mollusca, and it was not until 2005 that Ar-Ar dating on associated
      feldspar crystals in pumice clasts provided evidence for an even older age of
      ~195 ka. However, questions continue to be raised about the age and stratigraphic
      position of this crucial fossil specimen. Here we present direct U-series
      determinations on the Omo 1 cranium. In spite of significant methodological
      complications, which are discussed in detail, the results indicate that the human
      remains do not belong to a later intrusive burial and are the earliest
      representative of anatomically modern humans. Given the more archaic morphology
      shown by the apparently contemporaneous Omo 2 calvaria, we suggest that direct U
      series dating is applied to this fossil as well, to confirm its age in relation
      to Omo 1.

PMID- 22959816
TI  - Pharmacokinetics and pharmacodynamics of 'old' polymyxins: what is new?
AB  - 'Old' colistin and polymyxin B are increasingly used as last-line therapy against
      multidrug-resistant Gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter
      baumannii, and Klebsiella pneumoniae. For intravenous administration, colistin is
      dosed as its inactive prodrug colistin methanesulfonate (sodium), while polymyxin
      B is used as its sulfate (active antibacterial). Over the last decade,
      significant progress has been made in understanding their chemistry,
      pharmacokinetics (PK), and pharmacodynamics (PD). The first scientifically based
      dosing suggestions are now available for colistin methanesulfonate to generate a
      desired target steady-state plasma concentration of formed colistin in various
      categories of critically ill patients. As simply increasing polymyxin dosage
      regimens is not an option for optimizing their PK/PD due to nephrotoxicity,
      combination therapy with other antibiotics has great potential to maximize the
      efficacy of polymyxins while minimizing emergence of resistance. We must pursue
      rational approaches to the use of polymyxins and other existing antibiotics
      through the application of PK/PD principles.

PMID- 22959820
TI  - Muscle fatigue and contraction intensity modulates the complexity of surface
      electromyography.
AB  - Nonlinear dynamical techniques offer a powerful approach for the investigation of
      physiological time series. Multiscale entropy analyses have shown that
      pathological and aging systems are less complex than healthy systems and this
      finding has been attributed to degraded physiological control processes. A
      similar phenomenon may arise during fatiguing muscle contractions where surface
      electromyography signals undergo temporal and spectral changes that arise from
      the impaired regulation of muscle force production. Here we examine the affect of
      fatigue and contraction intensity on the short and long-term complexity of biceps
      brachii surface electromyography. To investigate, we used an isometric muscle
      fatigue protocol (parsed into three windows) and three contraction intensities (%
      of maximal elbow joint moment: 40%, 70% and 100%). We found that fatigue reduced
      the short-term complexity of biceps brachii activity during the last third of the
      fatiguing contraction. We also found that the complexity of surface
      electromyography is dependent on contraction intensity. Our results show that
      multiscale entropy is sensitive to muscle fatigue and contraction intensity and
      we argue it is imperative that both factors be considered when evaluating the
      complexity of surface electromyography signals. Our data contribute to a
      converging body of evidence showing that multiscale entropy can quantify subtle
      information content in physiological time series.

PMID- 22959821
TI  - Osmotic stress in Arctic and Antarctic strains of the green alga Zygnema
      (Zygnematales, Streptophyta): effects on photosynthesis and ultrastructure.
AB  - The osmotic potential and effects of plasmolysis on photosynthetic oxygen
      evolution and chlorophyll fluorescence were studied in two Arctic Zygnema sp.
      (strain B, strain G) and two Antarctic Zygnema sp. (strain E, strain D).
      Antarctic strain D was newly characterized by rbcL sequence analysis in the
      present study. The two Antarctic strains, D and E, are most closely related and
      may represent different isolates of the same species, in contrast, strain B and G
      are separate lineages. Incipient plasmolysis in the cells was determined by light
      microscopy after incubating cells in sorbitol solutions ranging between 200 mM
      and 1000 mM sorbitol for 3, 6 and 24h. In Zygnema strain B and G incipient
      plasmolysis occurred at ~600 mM sorbitol solution (720 mOsmol kg(-1), psi=-1.67
      MPa) and in strains D and E at ~300 mM (318 mOsmol kg(-1), psi=-0.8 MPa) sorbitol
      solution. Hechtian strands were visualized in all plasmolysed cells, which is
      particularly interesting, as these cells lack pores or plasmodesmata.
      Ultrastructural changes upon osmotic stress were a retraction of the condensed
      cytoplasm from the cell walls, damages to chloroplast and mitochondrial
      membranes, increasing numbers of plastoglobules in the chloroplasts and membrane
      enclosed particles in the extraplasmatic space. Maximum photosynthetic rates
      (P(max)) in light saturated range were between 145.5 MUmol O(2) h(-1)mg(-1)Chl a
      in Zygnema G and 752.9 MUmol O(2) h(-1)mg(-1)Chl a in Zygnema E. After incubation
      in 800 mM sorbitol for 3h P(max) decreased to the following percentage of the
      initial values: B: 16.3%, D: 16.8%, E: 26.1% and G: 35.0%. Osmotic stress (800 mM
      sorbitol) decreased maximum photochemical quantum yield of photosystem II
      (F(v)/F(m)) when compared to controls. Maximum values of relative electron
      transport rates of photosystem II (rETR(max)) decreased after incubation in 400
      mM sorbitol in Zygnema D and E, while they decreased in Zygnema B and G only
      after incubation in 800 mM sorbitol. The kinetics of the rETR curves were similar
      for the Arctic strains Zygnema B and G, but distinct from the Antarctic strains
      Zygnema D and E, which were similar when compared with each other. This suggests
      that the investigated Arctic Zygnema sp. strains might be better adapted to
      tolerate osmotic water stress than the investigated strains from the Antarctic.

PMID- 22959822
TI  - Walking stabilizes cognitive functioning in Alzheimer's disease (AD) across one
      year.
AB  - AD is a public health epidemic, which seriously impacts cognition, mood and daily
      activities; however, one type of activity, exercise, has been shown to alter
      these states. Accordingly, we sought to investigate the relationship between
      exercise and mood, in early-stage AD patients (N=104) from California, over a 1
      year period. Patients completed the Mini-Mental State Examination (MMSE),
      Geriatric Depression Scale (GDS), and Blessed-Roth Dementia Rating Scale (BRDRS),
      while their caregivers completed the Yale Physical Activity Survey (YALE),
      Profile of Mood States (POMS), the Neuropsychiatric Inventory (NPI) and
      Functional Abilities Questionnaire (FAQ). Approximately half of the participants
      were female, from a variety of ethnic groups (Caucasian=69.8%; Latino/Hispanic
      Americans=20.1%). Our results demonstrated that the patients spent little time
      engaged in physical activity in general, their overall activity levels decreased
      over time, and this was paired with a change in global cognition (e.g., MMSE
      total score) and affect/mood (e.g., POMS score). Patients were parsed into Active
      and Sedentary groups based on their Yale profiles, with Active participants
      engaged in walking activities, weekly, over 1 year. Here, Sedentary patients had
      a significant decline in MMSE scores, while the Active patients had an
      attenuation in global cognitive decline. Importantly, among the Active AD
      patients, those individuals who engaged in walking for more than 2 h/week had a
      significant improvement in MMSE scores. Structured clinical trials which seek to
      increase the amount of time AD patients were engaged in walking activities and
      evaluate the nature and scope of beneficial effects in the brain are warranted.

PMID- 22959824
TI  - Validation of a chiral liquid chromatography-tandem mass spectrometry method for
      the determination of pantoprazole in dog plasma.
AB  - Pantoprazole (PAN), a selective proton pump inhibitor, is used clinically as a
      racemic mixture for the treatment of acid-related gastrointestinal disorders. To
      investigate its stereoselective pharmacokinetics, a chiral liquid chromatography
      tandem mass spectrometry method was developed and validated to determine the
      pantoprazole enantiomers in dog plasma. After liquid-liquid extraction, a
      baseline resolution of enantiomers was achieved on an ovomucoid column using the
      mobile phase of methanol:acetonitrile:10mM ammonium formate (pH 7) (10.4:2.6:87,
      v/v/v) at 30 degrees C within 10min. Stable isotopically labeled (+)-d(3)
      pantoprazole and (-)-d(3)-pantoprazole were used as internal standards.
      Acquisition of mass spectrometric data was performed in multiple reaction
      monitoring mode via positive atmospheric pressure chemical ionization. The method
      was linear in the concentration range of 20.0-10,000ng/mL for each enantiomer
      using 25MUL of dog plasma. The lower limit of quantification (LLOQ) for each
      enantiomer was 20.0ng/mL. Intra- and inter-day precision ranged from 3.2% to
      10.3% for (+)-pantoprazole and 3.7-10.0% for (-)-pantoprazole. Accuracy varied
      from -1.4% to -0.2% for (+)-pantoprazole and -1.6% to 0.8% for (-)-pantoprazole.
      The validated method was applied successfully for stereoselective pharmacokinetic
      studies of racemic pantoprazole.

PMID- 22959823
TI  - 1,3-Bis(3,5-dichlorophenyl) urea compound 'COH-SR4' inhibits proliferation and
      activates apoptosis in melanoma.
AB  - The current clinical interventions in malignant melanomas are met with poor
      response to therapy due to dynamic regulation of multiple melanoma signaling
      pathways consequent to administration of single target agents. In this context of
      limited response to single target agents, novel candidate molecules capable of
      effectively inducing tumor inhibition along with targeting multiple critical
      nodes of melanoma signaling assume translational significance. In this regard, we
      investigated the anti-cancer effects of a novel dichlorophenyl urea compound
      called COH-SR4 in melanoma. The SR4 treatment decreased the survival and
      inhibited the clonogenic potential of melanomas along with inducing apoptosis in
      vitro cultures. SR4 treatments lead to inhibition of GST activity along with
      causing G2/M phase cell cycle arrest. Oral administration of 4 mg/kg SR4 leads to
      effective inhibition of tumor burdens in both syngeneic and nude mouse models of
      melanoma. The SR4 treatment was well tolerated and no overt toxicity was
      observed. The histopathological examination of resected tumor sections revealed
      decreased blood vessels, decrease in the levels of angiogenesis marker, CD31, and
      proliferation marker, Ki67, along with an increase in pAMPK levels. Western blot
      analyses of resected tumor lysates revealed increased PARP cleavage, Bim, pAMPK
      along with decreased pAkt, vimentin, fibronectin, CDK4 and cyclin B1. Thus, SR4
      represents a novel candidate for the further development of mono and
      combinatorial therapies to effectively target aggressive and therapeutically
      refractory melanomas.

PMID- 22959825
TI  - Multi-detection of preservatives in cheeses by liquid chromatography-tandem mass
      spectrometry.
AB  - The incorrect use of preservatives in cheeses may compromise food safety and
      damage consumers. According to the law, more than one preservative may be
      contemporarily used in cheeses. So a method for their contemporary detection may
      be useful for both manufacturers and control agencies quality control. In this
      research a liquid chromatography-tandem mass spectrometric with electrospray
      ionization method for the multi-determination of seven preservatives (benzoic
      acid, citric acid, hexamethylenetetramine, lysozyme, natamycin, nisin and sorbic
      acid) in cheese was developed. The preservatives were contemporarily extracted
      from cheese by a single procedure, and analyzed by RP-LC/ESI-MS/MS (Ion Trap) in
      positive ionization mode, with single reaction monitoring (SRM) acquisition.
      Three sample types (hard, pasta filata and fresh cheese) were used for method
      evaluation. Recoveries were mostly higher than 90%; MDLs ranged from 0.02 to 0.26
      mgkg(-1), and MQLs were included between 0.07 and 0.88 mgkg(-1). Due to matrix
      effect, quantitation was performed by referring to a matrix matched calibration
      curve, for each cheese typology. This method was also applied to commercial
      cheese samples, with good results. It appears fast, reliable and suitable for
      both screening and confirmation of the presence and quantitation of the
      preservatives in a single, multi-detection analysis.

PMID- 22959826
TI  - Diagnostic performance of whole brain volume perfusion CT in intra-axial brain
      tumors: preoperative classification accuracy and histopathologic correlation.
AB  - BACKGROUND: To evaluate the preoperative diagnostic power and classification
      accuracy of perfusion parameters derived from whole brain volume perfusion CT
      (VPCT) in patients with cerebral tumors. METHODS: Sixty-three patients (31 male,
      32 female; mean age 55.6 +/- 13.9 years), with MRI findings suspected of cerebral
      lesions, underwent VPCT. Two readers independently evaluated VPCT data. Volumes
      of interest (VOIs) were marked circumscript around the tumor according to maximum
      intensity projection volumes, and then mapped automatically onto the cerebral
      blood volume (CBV), flow (CBF) and permeability Ktrans perfusion datasets. A
      second VOI was placed in the contra lateral cortex, as control. Correlations
      among perfusion values, tumor grade, cerebral hemisphere and VOIs were evaluated.
      Moreover, the diagnostic power of VPCT parameters, by means of positive and
      negative predictive value, was analyzed. RESULTS: Our cohort included 32 high
      grade gliomas WHO III/IV, 18 low-grade I/II, 6 primary cerebral lymphomas, 4
      metastases and 3 tumor-like lesions. Ktrans demonstrated the highest sensitivity,
      specificity and positive predictive value, with a cut-off point of 2.21
      mL/100mL/min, for both the comparisons between high-grade versus low-grade and
      low-grade versus primary cerebral lymphomas. However, for the differentiation
      between high-grade and primary cerebral lymphomas, CBF and CBV proved to have
      100% specificity and 100% positive predictive value, identifying preoperatively
      all the histopathologically proven high-grade gliomas. CONCLUSION: Volumetric
      perfusion data enable the hemodynamic assessment of the entire tumor extent and
      provide a method of preoperative differentiation among intra-axial cerebral
      tumors with promising diagnostic accuracy.

PMID- 22959827
TI  - Correlation of 64 row MDCT, echocardiography and cardiac catheterization
      angiography in assessment of pulmonary arterial anatomy in children with cyanotic
      congenital heart disease.
AB  - OBJECTIVE: To study the correlation of low-dose 64-row multi-detector computed
      tomography (MDCT) with echocardiography and cardiac catheterization angiography
      (CCA) in the assessment of pulmonary arterial anatomy in children with cyanotic
      congenital heart disease (CCHD). MATERIALS AND METHODS: This prospective study
      included 105 children (74 males, 31 females) with CCHD, in the age group of 2
      months to 20 years, who underwent 64-row MDCT examination (low-dose CT protocol),
      echocardiography and CCA for the assessment of pulmonary arteries, including
      visualization, presence of confluence, stenosis and collaterals. Statistical
      analysis was performed using the non-parametric statistical analysis test to
      evaluate the concordance or discordance between echocardiography, MDCT and CCA.
      RESULTS: 64-row MDCT detected significantly more main and branch pulmonary
      arteries, patent pulmonary confluences, and more cases of pulmonary artery
      stenosis. CCA detected more major aorto-pulmonary collaterals than MDCT, whereas
      echocardiography failed to identify these major aorto-pulmonary collaterals. The
      effective CT radiation dose to patients less than 2 years of age was in the range
      of 0.7-2.5 mSv, where as the dose in patients more than 2 years of age ranged
      from that of 2.1 to 4.2 mSv, which is much less than the radiation dose reported
      in cardiac catheterization angiography. CONCLUSION: In cases where cardiac MRI
      cannot be performed, or is not sufficiently informative, low-dose 64-row MDCT
      correlates well with CCA and can provide adequate information about pulmonary
      arterial anatomy in children with cyanotic congenital heart disease, and can
      replace invasive cardiac catheterization angiography with markedly reduced
      radiation dosage to the patient.

PMID- 22959828
TI  - Novel mutations of ABCA1 transporter in patients with Tangier disease and
      familial HDL deficiency.
AB  - The objective of the study was the characterization of ABCA1 gene mutations in 10
      patients with extremely low HDL-cholesterol. Five patients (aged 6 months to 76
      years) presented with splenomegaly and thrombocytopenia suggesting the diagnosis
      of Tangier disease (TD). Three of them were homozygous for novel mutations either
      in intron (c.4465-34A>G) or in exons (c.4376delT and c.5449C>T), predicted to
      encode truncated proteins. One patient was compound heterozygous for a nucleotide
      insertion (c.1758_1759insG), resulting in a truncated protein and for a
      nucleotide substitution c.4799A>G, resulting in a missense mutation (p.H1600R).
      The last TD patient, found to be heterozygous for a known mutation (p.D1009Y),
      had a complete defect in ABCA1-mediated cholesterol efflux in fibroblasts,
      suggesting the presence of a second undetected mutant allele. Among the other
      patients, four were asymptomatic, but one, with multiple risk factors, had severe
      peripheral artery disease. Three of these patients were heterozygous for known
      mutations (p.R130K+p.N1800H, p.R1068C, p.N1800H), while two were carriers of
      novel mutations (c.1195-27G>A and c.396_397insA), predicted to encode truncated
      proteins. The pathogenic effect of the two intronic mutations (c. 1195-27G>A and
      c.4465-34A>G) was demonstrated by the analysis of the transcripts of splicing
      reporter mutant minigenes expressed in COS-1 cells. Both mutations activated an
      intronic acceptor splice site which resulted in a partial intron retention in
      mature mRNA with the production of truncated proteins. This study confirms the
      allelic heterogeneity of TD and suggests that the diagnosis of TD must be
      considered in patients with an unexplained splenomegaly, associated with
      thrombocytopenia and hypocholesterolemia.

PMID- 22959829
TI  - Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles
      phosphomannomutase 2 deficiency.
AB  - We report on the seventh known patient with S-adenosylhomocysteine hydrolase
      (SAHH) deficiency presenting at birth with features resembling phosphomannomutase
      2 (PMM2-CDG Ia) deficiency. Plasma methionine and total homocysteine levels were
      normal at 2 months and increased only after the 8th month of age. SAHH deficiency
      was confirmed at 4.5 years of age by showing decreased SAHH activity (11% in both
      erythrocytes and fibroblasts), and compound heterozygosity for a known mutation
      c.145C>T (p.R49C) and a novel variant c.211G>A (p.G71S) in the AHCY gene.
      Retrospective analysis of clinical features revealed striking similarities
      between SAHH deficiency and the PMM2-CDG Ia.

PMID- 22959830
TI  - Reply: To PMID 22527748.

PMID- 22959831
TI  - Stress and pain response of neonates after spontaneous birth and vacuum-assisted
      and cesarean delivery.
AB  - OBJECTIVE: The objective of the study was to compare the stress response and pain
      expression of newborns (NBs) in the early postpartum period. STUDY DESIGN: This
      was a prospective study with 280 NBs enclosed at 3 Swiss university hospitals.
      Stress response and pain reaction were analyzed according to the mode of
      delivery: elective cesarean section (ELCS), spontaneous vaginal delivery, and
      assisted vaginal delivery by vacuum extraction (VE). Saliva cortisol and clinical
      pain expression were evaluated after delivery and before and after heel prick for
      metabolic screening. RESULTS: Significant differences were evident during the
      first 72 hours postpartum with highest nominations in the VE group. Meconium
      stained amniotic fluid was the only intrapartum stress factor with an impact on
      clinical pain expression. CONCLUSION: NBs delivered vaginally show a higher
      incidence of stress response and pain expression than infants of the ELCS group.
      The long-term impact of these findings remains to be determined.

PMID- 22959832
TI  - Gestational age at delivery and perinatal outcomes of twin gestations.
AB  - OBJECTIVE: The optimal gestational duration for twin gestations is unknown.
      Epidemiologic studies show that the lowest perinatal mortality rate for twins is
      at 37-38 weeks, but these studies lack information on pregnancy complications and
      neonatal morbidities. This study evaluates pregnancy characteristics and
      perinatal outcomes of twins in order to assess the optimal gestational age for
      delivery. STUDY DESIGN: This is a retrospective study of twins delivered at >=36
      weeks at our institution from 1991-2009. The composite rate of perinatal
      morbidity and mortality (including perinatal death, respiratory distress,
      suspected sepsis, and need for neonatal intensive care) was determined for weekly
      intervals from 36-39(+) weeks. RESULTS: There were 377 twin gestations included.
      Of those 83% were dichorionic. Fifty-three percent had spontaneous labor and 48%
      were delivered by cesarean section. Perinatal outcomes improved as gestational
      age advanced to 38 weeks. CONCLUSION: Perinatal morbidity and mortality rates
      suggest that the optimal time for delivery of twins is at 38 weeks or greater.

PMID- 22959833
TI  - The efficacy of early amniotomy in nulliparous labor induction: a randomized
      controlled trial.
AB  - OBJECTIVE: The purpose of this study was to assess whether early amniotomy
      reduces the duration of labor or increases the proportion of subjects who are
      delivered within 24 hours in nulliparous patients who undergo labor induction.
      STUDY DESIGN: We performed a randomized controlled trial that compared early
      amniotomy to standard management in nulliparous labor inductions. Inclusion
      criteria were nulliparity, singleton, term gestation, and a need for labor
      induction. Subjects were assigned randomly to early amniotomy (artificial rupture
      of membranes, <=4 cm) or to standard treatment. There were 2 primary outcomes:
      (1) time from induction initiation to delivery and (2) the proportion of women
      who delivered within 24 hours. RESULTS: Early amniotomy shortens the time to
      delivery by >2 hours (19.0 vs 21.3 hours) and increases the proportion of induced
      nulliparous women who deliver within 24 hours (68% vs 56%). These improvements in
      labor outcomes did not come at the expense of increased complications.
      CONCLUSION: Early amniotomy is a safe and efficacious adjunct in nulliparous
      labor inductions.

PMID- 22959834
TI  - Biological activity of glycolipids produced by microorganisms: new trends and
      possible therapeutic alternatives.
AB  - Several biological processes in prokaryotic and eukaryotic organisms require the
      presence of glycolipids (biosurfactants), compounds with both hydrophilic and
      hydrophobic groups in their structure. They constitute the backbone of different
      metabolic functions and biological structures such as cell membranes. Besides
      being structural components, glycolipids show surface activity in the interfaces
      and are mainly produced by microorganisms. Interest in biosurfactants has
      increased considerably in recent times due to their applications in the
      environmental, oil, food, and pharmaceutical industries, since they have unique
      properties such as low toxicity, high biodegradability, environmentally friendly,
      foaming capacity, high selectivity and specificity at extreme temperatures, pH
      and salinity, as well as biological activity. All of these properties are
      considered advantages over other chemical surfactants, and therefore glycolipids
      are considered a good alternative, given the current interest on sustainable
      development. The present work shows a general view of bio-surfactants of
      microbial origin, particularly of glycolipids, referring to several studies on
      their biological activity that have revealed their great potential in the medical
      biological field, discovering interesting possibilities for their therapeutic
      application in the near future.

PMID- 22959835
TI  - Mass-mobility characterization of flame-made ZrO2 aerosols: primary particle
      diameter and extent of aggregation.
AB  - Gas-borne nanoparticles undergoing coagulation and sintering form irregular or
      fractal-like structures affecting their transport, light scattering, effective
      surface area, and density. Here, zirconia (ZrO(2)) nanoparticles are generated by
      scalable spray combustion, and their mobility diameter and mass are obtained
      nearly in situ by differential mobility analyzer (DMA) and aerosol particle mass
      (APM) measurements. Using these data, the density of ZrO(2) and a power law
      between mobility and primary particle diameters, the structure of fractal-like
      particles is determined (mass-mobility exponent, prefactor and average number,
      and surface area mean diameter of primary particles, d(va)). The d(va) determined
      by DMA-APM measurements and this power law is in good agreement with the d(va)
      obtained by ex situ nitrogen adsorption and microscopic analysis. Using this
      combination of measurements and above power law, the effect of flame spray
      process parameters (e.g., precursor solution and oxygen flow rate as well as
      zirconium concentration) on fractal-like particle structure characteristics is
      investigated in detail. This reveals that predominantly agglomerates (physically
      bonded particles) and aggregates (chemically- or sinter-bonded particles) of
      nanoparticles are formed at low and high particle concentrations, respectively.

PMID- 22959836
TI  - Muscle-tendon units provide limited contributions to the passive stiffness of the
      index finger metacarpophalangeal joint.
AB  - The passive stiffness at the MCP joint is a result of the elasticity of muscle
      tendon units (MTUs) and capsule ligament complex (CLC), however, the relative
      contributions of these two components are unknown. We hypothesize that the MTUs
      provide the majority of the contributions to the joint stiffness by generating
      resistive forces when the MCP joint is flexed or extended. We used the work done
      by passive moments as a measure for the determination of the contributions to the
      joint stiffness. We conducted experiments with ten human subjects and collected
      joint angle and finger tip force data. The total passive moment and joint angle
      data were fitted with a double exponential model, and the passive moments due to
      the MTUs were determined by developing subject-specific models of the passive
      force-length change relationships. Our results show that for all the subjects,
      the work done by the passive moments from the MTUs is less than 50% of the total
      work done, and the CLC provides dominant contributions to the joint stiffness
      throughout the flexion-extension range of the joint angle. Therefore, the
      hypothesis that the MTUs provide the majority of the contributions to the MCP
      joint stiffness is not supported. We also determined that the majority of the
      MTUs passive moment was generated by the extrinsic MTUs and the contributions of
      the intrinsic MTUs was negligible.

PMID- 22959837
TI  - How much muscle strength is required to walk in a crouch gait?
AB  - Muscle weakness is commonly cited as a cause of crouch gait in individuals with
      cerebral palsy; however, outcomes after strength training are variable and
      mechanisms by which muscle weakness may contribute to crouch gait are unclear.
      Understanding how much muscle strength is required to walk in a crouch gait
      compared to an unimpaired gait may provide insight into how muscle weakness
      contributes to crouch gait and assist in the design of strength training
      programs. The goal of this study was to examine how much muscle groups could be
      weakened before crouch gait becomes impossible. To investigate this question, we
      first created muscle-driven simulations of gait for three typically developing
      children and six children with cerebral palsy who walked with varying degrees of
      crouch severity. We then simulated muscle weakness by systematically reducing the
      maximum isometric force of each muscle group until the simulation could no longer
      reproduce each subject's gait. This analysis indicated that moderate crouch gait
      required significantly more knee extensor strength than unimpaired gait. In
      contrast, moderate crouch gait required significantly less hip abductor strength
      than unimpaired gait, and mild crouch gait required significantly less ankle
      plantarflexor strength than unimpaired gait. The reduced strength required from
      the hip abductors and ankle plantarflexors during crouch gait suggests that
      weakness of these muscle groups may contribute to crouch gait and that these
      muscle groups are potential targets for strength training.

PMID- 22959838
TI  - The successes and challenges of life course epidemiology: a commentary on Gibb,
      Fergusson and Horwood (2012).

PMID- 22959839
TI  - Deformable segmentation via sparse representation and dictionary learning.
AB  - "Shape" and "appearance", the two pillars of a deformable model, complement each
      other in object segmentation. In many medical imaging applications, while the low
      level appearance information is weak or mis-leading, shape priors play a more
      important role to guide a correct segmentation, thanks to the strong shape
      characteristics of biological structures. Recently a novel shape prior modeling
      method has been proposed based on sparse learning theory. Instead of learning a
      generative shape model, shape priors are incorporated on-the-fly through the
      sparse shape composition (SSC). SSC is robust to non-Gaussian errors and still
      preserves individual shape characteristics even when such characteristics is not
      statistically significant. Although it seems straightforward to incorporate SSC
      into a deformable segmentation framework as shape priors, the large-scale sparse
      optimization of SSC has low runtime efficiency, which cannot satisfy clinical
      requirements. In this paper, we design two strategies to decrease the
      computational complexity of SSC, making a robust, accurate and efficient
      deformable segmentation system. (1) When the shape repository contains a large
      number of instances, which is often the case in 2D problems, K-SVD is used to
      learn a more compact but still informative shape dictionary. (2) If the derived
      shape instance has a large number of vertices, which often appears in 3D
      problems, an affinity propagation method is used to partition the surface into
      small sub-regions, on which the sparse shape composition is performed locally.
      Both strategies dramatically decrease the scale of the sparse optimization
      problem and hence speed up the algorithm. Our method is applied on a diverse set
      of biomedical image analysis problems. Compared to the original SSC, these two
      newly-proposed modules not only significant reduce the computational complexity,
      but also improve the overall accuracy.

PMID- 22959840
TI  - Minor cartilage collagens type IX and XI are expressed during embryonic stem cell
      derived in vitro chondrogenesis.
AB  - Cartilage development is a complex process that can be analyzed using numerous
      model systems. We have previously shown that in vitro differentiation of murine
      embryonic stem (ES) cells via embryoid bodies (EBs) recapitulates the cellular
      differentiation steps of chondrogenesis. However, differentiated chondrocytes
      lose their characteristic phenotype when they are kept in monolayer culture. This
      dedifferentiation process is one of the main obstacles of cartilage tissue
      engineering and could not be analyzed using the EB model system. The aim of this
      study was to further characterize the chondrogenic nodules derived by in vitro
      differentiation of murine ES cells for the distribution of collagen types II, IX
      and XI in comparison to in vitro dedifferentiating primary chondrocytes from
      murine embryonic ribs. Expression of cartilage collagens and other extracellular
      matrix proteins was analyzed using immunostaining, cytochemical stainings and
      quantitative RT-PCR. We show that ES cell-derived chondrocyte differentiation
      starts with mesenchymal condensations synthesizing high amounts of fibronectin.
      Later, the matrix of the mature cartilage nodules consists of type II collagen,
      proteoglycans and the minor collagens type IX and XI. The nodules show a three
      dimensional structure with multiple layers of collagen type II-positive cells. At
      late differentiation stages these chondrocytes were located at lateral regions of
      the nodules. Similar to the distribution pattern of collagen type II positive
      cells, the cells staining positive for collagen type IX and XI were present in
      the surface regions, but not in the central areas of the chondrogenic nodules.
      During cultivation of the primary murine rib chondrocytes expression of
      chondrogenic marker genes such as collagen type II and aggrecan declined and many
      chondrocytes lost characteristic cartilage matrix proteins and converted to an
      elongated, fibroblastoid shape with prominent actin stress fibers. Chondrogenic
      differentiation of murine ES cells combined with monolayer culture of embryonic
      rib chondrocytes is a valuable tool to study changes in the expression pattern
      during differentiation and dedifferentiation of chondrocytes.

PMID- 22959842
TI  - Monitoring of aortic valve opening and systolic aortic insufficiency in
      optimization of continuous-flow left ventricular assist device settings.

PMID- 22959841
TI  - In vivo repair of alkylating and oxidative DNA damage in the mitochondrial and
      nuclear genomes of wild-type and glycosylase-deficient Caenorhabditis elegans.
AB  - Base excision repair (BER) is an evolutionarily conserved DNA repair pathway that
      is critical for repair of many of the most common types of DNA damage generated
      both by endogenous metabolic pathways and exposure to exogenous stressors such as
      pollutants. Caenorhabditis elegans is an increasingly important model organism
      for the study of DNA damage-related processes including DNA repair, genotoxicity,
      and apoptosis, but BER is not well understood in this organism, and has not
      previously been measured in vivo. We report robust BER in the nuclear genome and
      slightly slower damage removal from the mitochondrial genome; in both cases the
      removal rates are comparable to those observed in mammals. However we could
      detect no deficiency in BER in the nth-1 strain, which carries a deletion in the
      only glycosylase yet described in C. elegans that repairs oxidative DNA damage.
      We also failed to detect increased lethality or growth inhibition in nth-1
      nematodes after exposure to oxidative or alkylating damage, suggesting the
      existence of at least one additional as-yet undetected glycosylase.

PMID- 22959843
TI  - Accidental, unintentional reprogramming of a temporary external pacemaker leading
      to R-on-T and cardiac arrest.

PMID- 22959844
TI  - Recent development of cyclodextrin chiral stationary phases and their
      applications in chromatography.
AB  - The current article reviews the development and applications of novel
      cyclodextrin chiral stationary phases (CD-CSPs) in liquid chromatography (LC),
      capillary electrochromatography (CEC), gas chromatography (GC) and supercritical
      fluid chromatography (SFC) over the period of January 2007 to March 2012. The
      synthetic routes of CD-CSPs, as well as the presence of selective functional
      groups in effecting inclusion complexation and molecular interactions have been
      found to exert profound influence in the enantioseparation process. In this
      article, various synthetic and functional groups immobilization strategies of
      novel CD-CSPs, and their applications in chiral resolution using different
      chromatography techniques are discussed. After introducing the topic in Section
      1, Section 2 describes novel CD-CSPs in LC applications, where the CSPs are
      classified according to its coating approaches (physical and chemical manners)
      for ease of readership. Section 3 discusses recent development of CD-CSPs in open
      tubular CEC (OT-CEC), packed-bed CEC (P-CEC), pseudostationary phase CEC (PSP
      CEC) and monolithic CEC. The last part illustrates novel CD-CSPs in gas
      chromatography (GC) and supercritical fluid chromatography (SFC).

PMID- 22959845
TI  - Sensitive enantioseparation by transient trapping-cyclodextrin electrokinetic
      chromatography.
AB  - An on-line sample preconcentration based on transient trapping was applied to
      cyclodextrin electrokinetic chromatography (CDEKC) to realize a highly sensitive
      chiral analysis in capillary electrophoresis. The partial introduction of a
      micellar solution before the electrokinetic injection of a sample solution
      provided the effective preconcentration and enantioseparation of chiral
      compounds, resulting in the up to 240-fold enhancements of peak intensity and 100
      fold improvements of limit of detection of (R),(S)-1-aminoindan as the model
      analyte. The demonstrated method could be applied to the other pharmaceutical
      compounds, which allowed five chiral analytes to be resolved with 40- to 160-fold
      sensitivity enhancements at once. The enantioseparation efficiency of the
      proposed method was slightly lower as compared to the conventional CDEKC, while
      the acceptable baseline separations of enantiomers were obtained in transient
      trapping-CDEKC relative to the undesirable resolution in the CDEKC with other
      preconcentration techniques. Additionally, it was clarified that transient
      trapping-CDEKC was also applicable to the analysis of enantiomeric excess,
      providing the sensitive detection of 43ppb of (R)-chlorpheniramine in 5ppm (S)
      chlorpheniramine solution commercially available.

PMID- 22959846
TI  - Determination of sedatives and adrenergic blockers in blood meal using
      accelerated solvent extraction and Orbitrap mass spectrometry.
AB  - The detection of veterinary drugs in blood meal is needed since it is used as an
      environment-friendly agricultural material despite its origination from animal
      blood. A method using accelerated solvent extraction and liquid chromatographic
      linear ion trap quadrupole Orbitrap mass spectrometry was developed to determine
      sedatives and adrenergic blockers in blood meal. The determination method was
      established following optimizations of accelerated solvent extraction, dispersive
      solid-phase extraction and high resolution mass spectrometric detection.
      Linearity, sensitivity, accuracy, repeatability and reproducibility of the method
      were fully validated. The method was applied to commercial blood meal products.

PMID- 22959847
TI  - Improved gas chromatography-tandem mass spectrometry determination of pesticide
      residues making use of atmospheric pressure chemical ionization.
AB  - The capabilities of a recently launched atmospheric pressure chemical ionization
      (APCI) source for mass spectrometry (MS) coupled to gas chromatography (GC) have
      been tested in order to evaluate its potential in pesticide residue analysis in
      fruits and vegetables. Twenty-five pesticides were selected due to their high
      fragmentation under electron ionization (EI), making that the molecular ion (M+)
      is practically absent in their spectra. The fragmentation of these pesticides
      under APCI conditions was studied, with the result that M+ was not only present
      but also highly abundant for most compounds, with noticeable differences in the
      fragmentation patterns in comparison with EI. Moreover, the addition of water as
      modifier was tested to promote the formation of protonated molecules ([M+H]+).
      Under these conditions, [M+H]+ became the base peak of the spectrum for the
      majority of compounds, thus leading to an increase of sensitivity in the
      subsequent GC-MS/MS method developed using triple quadrupole analyzer (QqQ).
      Highly satisfactory sensitivity and precision, in terms of repeatability, were
      reached and linearity was satisfactory in the range 0.01-100 ng/mL. The developed
      methodology was applied to apple, orange, tomato and carrot QuEChERS fortified
      extracts in order to evaluate the matrix effects. In summary, the soft and
      reproducible ionization in the APCI source has greatly favored the formation of
      [M+H]+ oppositely to EI where abundant fragmentation occurs and where the
      molecular ions have low abundance or are even absent in the mass spectrum. In
      this way, the use of APCI has facilitated the development of tandem MS methods
      based on the selection of abundant [M+H]+ as precursor ion.

PMID- 22959848
TI  - Optimizing the electrode size of circular bimorph plates with different boundary
      conditions for maximum deflection of piezoelectric micromachined ultrasonic
      transducers.
AB  - The effect of plate electrode area on the deflection of a symmetric circular
      bimorph piezoelectric micromachined ultrasonic transducer (pMUT) with clamped and
      simply supported boundary conditions was studied for the first time. Distinct
      plate displacement shape functions were defined for the regions underneath and
      outside the active electrodes. The plate shape functions were solved analytically
      using classic plate theory in conjunction with the external boundary conditions
      and the internal ones between the two regions in order to calculate the exact
      plate displacement under both external voltage stimulus and acoustic pressure.
      The model was used to study the effect of the electrode area on the overall plate
      deflection per unit input voltage such that the electromechanical coupling is
      optimized. While the center plate deflection increased monotonically with the
      electrode area for a simply supported plate, it followed a parabolic shape for a
      clamped one with a maximum deflection when the electrode radius covered 60% of
      the total plate radius. The simply supported plate exhibited four times the plate
      deflection capability of its clamped counterpart, when both are operating at
      their optimal electrode size. Both an experimental clamped bimorph aluminum
      nitride (AlN) pMUT, recently reported in the literature, and Finite Element
      Modeling (FEM) were used to verify the developed model. The theoretical model
      predicted a static displacement per unit voltage of 10.9nm/V and a resonant
      frequency of 196.5kHz, which were in excellent agreement with the FEM results of
      10.32nm/V and 198.5kHz, respectively. The modeling data matched well with the
      experimental measurements and the error ranged from 2.7-22% due to process
      variations across the wafer. As such, the developed model can be used to design
      more sensitive pMUTs or extract the flexural piezoelectric coefficient using
      piezoelectrically actuated circular plates.

PMID- 22959849
TI  - Posttraumatic delayed cranio-orbital cerebrospinal fluid leakage: case report.
AB  - A 56-year-old man sustained subarachnoid haemorrhage, skull base fracture and
      multiple facial fractures in a traffic accident. Two weeks later, the patient
      developed a subperiosteal fluid collection into the orbit of the right side
      presenting with a progressive proptosis and an increased intraocular pressure. We
      performed drainage of the fluid on the superior part of the right orbit, followed
      by a surgical reduction of the facial fractures. The patient had no exophthalmos
      any longer, whose intraocular pressure was normalised. In conclusion, our case
      indicates that careful monitoring of clinical signs and a follow-up radiography
      would be mandatory for patients with craniocerebral trauma despite a lack of the
      definite symptoms. Clinicians should consider the possibility that the
      cerebrospinal fluid (CSF) leakage into the orbit might occur in these patients.

PMID- 22959850
TI  - The use of ultrasound for the assessment of enthesitis in patients with
      spondyloarthritis.
AB  - Seronegative spondyloarthritis (SpA) represents a group of diseases that share
      certain genetic, clinical, and radiographic features. Enthesitis, inflammation at
      the site of tendon insertion into the bone, involving both the axial and the
      peripheral joints, is an important sign of SpA. Clinical diagnosis of enthesitis,
      however, is neither sensitive nor specific; thus, the diagnosis of enthesitis
      often relies on typical abnormalities in imaging studies. Due to its low costs
      and availability, ultrasound is emerging as the preferred technique for detection
      of enthesitis for both clinical and research purposes. Ultrasonographic features
      of enthesitis include tendon hypoechogenicity and thickening, calcifications,
      bone erosions, and Doppler signal. Several semi-quantitative scoring systems have
      been developed to quantify ultrasonographic abnormalities of the entheses. These
      methods have been used for early diagnosis and classification of SpA as well as
      for monitoring response to treatment.

PMID- 22959851
TI  - MRI in hypertrophic mono- and polyneuropathies.
AB  - Different conditions that may lead to enlarged nerves or nerve roots include
      hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF) type 1,
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and intraneural
      perineurioma. Differential diagnosis of hypertrophic mono- and
      polyradiculopathies remains challenging but is important because of different
      treatments and prognosis. Magnetic resonance imaging (MRI) can identify the
      hypertrophic nerve segments and guide a fascicular biopsy. A fascicular biopsy
      will often be necessary for precise diagnosis.

PMID- 22959852
TI  - Should warfarin or aspirin be stopped prior to prostate biopsy? An analysis of
      bleeding complications related to increasing sample number regimes.
AB  - AIM: To determine whether patients undergoing transrectal ultrasound (TRUS)
      guided prostate biopsy with increased sampling numbers are more likely to
      experience bleeding complications and whether warfarin or low-dose aspirin are
      independent risk factors. MATERIALS AND METHODS: 930 consecutive patients with
      suspected prostatic cancer were followed up after biopsy. Warfarin/low-dose
      aspirin was not stopped prior to the procedure. An eight to 10 sample regime TRUS
      guided prostate biopsy was performed and patients were offered a questionnaire to
      complete 10 days after the procedure, to determine any immediate or delayed
      bleeding complications. RESULTS: 902 patients returned completed questionnaires.
      579 (64.2%) underwent eight core biopsies, 47 (5.2%) underwent nine, and 276
      (30.6%) underwent 10. 68 were taking warfarin [mean international normalized
      ratio (INR) = 2.5], 216 were taking low-dose aspirin, one was taking both, and
      617 were taking neither. 27.9% of those on warfarin and 33.8% of those on aspirin
      experienced haematuria. 37% of those on no blood-thinning medication experienced
      haematuria. 13.2% of those on warfarin and 14.4% of those on aspirin experienced
      rectal bleeding. 11.5% of those on no blood-thinning medication experienced
      rectal bleeding. 7.4% of those on warfarin and 12% of those on aspirin
      experienced haematospermia. 13.8% of those on neither experienced haematospermia.
      Regression analysis showed a significant association between increasing sampling
      number and occurrence of all bleeding complication types. There was no
      significant association between minor bleeding complications and warfarin use;
      however, there was a significant association between minor bleeding complications
      and low-dose aspirin use. There was no severe bleeding complication. CONCLUSION:
      There is an increased risk of bleeding complications following TRUS-guided
      prostate biopsy with increased sampling numbers but these are minor. There is
      also an increased risk with low-dose aspirin use; however, there is no increased
      risk of bleeding complications with warfarin use. These results suggest that up
      to 10 cores during prostate biopsy remains acceptable safe practice and cessation
      of warfarin and low-dose aspirin is usually not necessary.

PMID- 22959853
TI  - Spectroscopic analysis of polymerization and exonuclease proofreading by a high
      fidelity DNA polymerase during translesion DNA synthesis.
AB  - High fidelity DNA polymerases maintain genomic fidelity through a series of
      kinetic steps that include nucleotide binding, conformational changes, phosphoryl
      transfer, polymerase translocation, and nucleotide excision. Developing a
      comprehensive understanding of how these steps are coordinated during correct and
      pro-mutagenic DNA synthesis has been hindered due to lack of spectroscopic
      nucleotides that function as efficient polymerase substrates. This report
      describes the application of a non-natural nucleotide designated 5-naphthyl
      indole-2'-deoxyribose triphosphate which behaves as a fluorogenic substrate to
      monitor nucleotide incorporation and excision during the replication of normal
      DNA versus two distinct DNA lesions (cyclobutane thymine dimer and an abasic
      site). Transient fluorescence and rapid-chemical quench experiments demonstrate
      that the rate constants for nucleotide incorporation vary as a function of DNA
      lesion. These differences indicate that the non-natural nucleotide can function
      as a spectroscopic probe to distinguish between normal versus translesion DNA
      synthesis. Studies using wild-type DNA polymerase reveal the presence of a
      fluorescence recovery phase that corresponds to the formation of a pre-excision
      complex that precedes hydrolytic excision of the non-natural nucleotide. Rate
      constants for the formation of this pre-excision complex are dependent upon the
      DNA lesion, and this suggests that the mechanism of exonuclease proofreading is
      regulated by the nature of the formed mispair. Finally, spectroscopic evidence
      confirms that exonuclease proofreading competes with polymerase translocation.
      Collectively, this work provides the first demonstration for a non-natural
      nucleotide that functions as a spectroscopic probe to study the coordinated
      efforts of polymerization and exonuclease proofreading during correct and
      translesion DNA synthesis.

PMID- 22959854
TI  - Reply to John E. Madias, MD, FACC, FAHA: MTWA and/or LVEF in ischemic
      cardiomyopathy.

PMID- 22959855
TI  - Red blood cell distribution width predicts mortality after coronary artery bypass
      grafting.

PMID- 22959856
TI  - Giant left atrium due to mitral stenosis with massive atelectasis: a successful
      case with perioperative approach.

PMID- 22959857
TI  - [Intensive dietary advice program in primary care].
AB  - A sedentary lifestyle and inappropriate eating habits are the main causes of
      major diseases (cardiovascular diseases, type 2 diabetes, and certain types of
      cancers), as well as a high morbidity and mortality. The Dietary Advice program
      was designed by the Andalusian Health Department to promote healthy habits (i.e.
      physical exercise and a balanced diet) to prevent secondary diseases. This
      program is organised in two phases: Basic Dietary Advice and Intensive Dietary
      Advice. This paper aims to describe the interventions protocol on the intensive
      dietary phase of the program focused on the promotion on changes in people's
      lifestyles from a multi-factorial approach. The program consisted of two
      individual nurse visits, five workshops and nursing follow up clinics. The
      individual visits ensured that the team learned of each person needs; likewise,
      the group activities were aimed at improving the transmission of knowledge and
      the acquisition of skills, abilities and attitudes towards healthier lifestyles.

PMID- 22959858
TI  - Malvidin-3-glucoside protects endothelial cells up-regulating endothelial NO
      synthase and inhibiting peroxynitrite-induced NF-kB activation.
AB  - Anthocyanins are the most abundant flavonoid constituents of fruits and
      vegetables and several epidemiological studies suggest that the consumption of
      these compounds protect against several diseases, including vascular disorders.
      Previously, we have reported that anthocyanins are able to counteract
      peroxynitrite-induced apoptotic effects in endothelial cells through inhibition
      of several crucial signaling cascades, upstream and downstream of mitochondria.
      Following these studies, here we investigated possible effects of malvidin-3
      glucoside, one of the main dietary anthocyanins, on NO bioavailability and on
      peroxynitrite-induced NF-kB activation in the same cell model. Our results show
      that treatment of bovine arterial endothelial cells with malvidin-3-glucoside up
      regulated eNOS mRNA, leading to the enhancement of eNOS activity and NO
      production, an effect even greater when cells were further stimulated with
      peroxynitrite. On the other hand, in these activated endothelial cells, malvidin
      3-glucoside suppressed pro-inflammatory mediators, namely iNOS expression/NO
      biosynthesis, COX-2 expression and IL-6 production, through inhibition of NF-kB
      activation. These findings suggest a potential role of malvidin-3-glucoside in NO
      balance and in inhibition of pro-inflammatory signaling pathways, supporting its
      benefits in cardiovascular health and pointing to anthocyanins as a promising
      tool for development of functional foods and nutraceuticals to improve
      endothelial function.

PMID- 22959859
TI  - Impact of a new model of intensive care medicine upon healthcare in a department
      of intensive care medicine.
AB  - OBJECTIVES: To evaluate a new organizational model in an intensive care unit,
      with the implementation of early warning systems and a support unit. DESIGN: A
      retrospective, comparative cohort study was carried out. SETTING: The study was
      carried out in the Department of Intensive Care Medicine (DICM) of a tertiary
      hospital (2009-2011), with the comparison of three time periods (P1, P2 and P3)
      that differed in terms of organization and logistics. PATIENTS: We analyzed all
      patients admitted to the ICU during the study period. Patients from maternal and
      infant intensive care were excluded. VARIABLES OF INTEREST: Percentage of
      patients with stays of under two days, with invasiveness used; readmission to the
      DICM, type of admission and percentage of stays of longer than one month; APACHE
      II score, mean stay in the ICU and shift distribution of the admissions. RESULTS:
      We analyzed a sample of 3209 patients (65% males), with a mean age of 58.23
      (18.23) years, a mean APACHE II score of 16.67 (8.23), and presenting an
      occupancy rate of 7.3 (10.3) days in the analyzed period. The ratio APACHE II
      score/number of beds was 0.69 (0.34) in P1, compared to 0.68 (0.33) in P2 and
      0.76 (0.37) in P3 (p<0.001). The intervention surveillance grade (grade 1) was
      42% (39-46%) in P1, 40% (37-43%) in P2 and 31% (28-35%) in P3 (p<0.001). The
      average stay in the ICU ranged from 7.10 days (8.82) in P1 to 6.60 days (9.49) in
      P2 and 8.42 days (12.73) in P3 (p<0.001). CONCLUSIONS: There has been an increase
      in the number of patients seen in our DICM, with a decrease in the patients
      admitted to the conventional ICU. Patients now admitted to the ICU are more
      seriously ill, require a greater level of intervention, and give rise to an
      increase in the mean duration of stay in the ICU.

PMID- 22959860
TI  - [Results of an artificial airway management protocol in critical patients
      subjected to mechanical ventilation].
AB  - OBJECTIVE: To determine the results of the implementation of a protocol in an
      intensive care unit (ICU) referred to critically ill patients requiring a
      prolonged artificial airway. DESIGN: A prospective, observational cohort study
      was carried out. INTERVENTION: Management strategies were established on the
      airway by endotracheal intubation (ETI) or tracheostomy, and guidelines were
      developed for action in the decannulation process. SETTING: A polyvalent ICU.
      PATIENTS: We studied 169 patients subjected to mechanical ventilation (MV), 67
      with ETI >= 10 days of MV and 102 with percutaneous (PT) or surgical tracheostomy
      (TQ). VARIABLES OF INTEREST: ICU and hospital stays, days of ETI and MV,
      mortality, tracheostomy, anatomical risk factors, surgical complications, and
      postoperative decannulation period. RESULTS: ETI versus tracheotomy involved
      fewer days of MV (17 vs. 30 days, p<0.001), a shorter ICU stay (20 vs. 35 days,
      p<0.001), and a shorter hospital stay (34 vs. 51 days, p<0.001).There were more
      TQ procedures in patients with risk factors (47% TP vs. 89% TQ, p<0.001).
      Intraoperative minor bleeding was the most common complication, being associated
      with TQ (31% vs. 11%, p = 0.03). TP was associated with a shorter
      cannulationperiod (25 days vs. 34 days, p<0.04). CONCLUSIONS: The protocol
      variants showed no differences in terms of complications and mortality, when
      orienting application to patients with similar characteristics.

PMID- 22959861
TI  - A novel method for the large-scale production of PG-CNP37, a C-type natriuretic
      peptide analogue.
AB  - Achondroplasia is the most common form of human dwarfism caused by a mutation in
      the fibroblast growth factor receptor 3 (FGFR3), resulting in abnormal
      endochondral bone formation. C-type natriuretic peptide (CNP) is a potent
      stimulator of endochondral bone growth and represents a potential therapy for
      achondroplasia. We have developed a novel, simple and cost effective method to
      produce a CNP analogue, PG-CNP37, at a large scale from Escherichia coli. A PG
      CNP37 fusion protein was over-expressed as inclusion bodies in E. coli, which
      were purified then cleaved by formic acid to release the PG-CNP37 peptide.
      Approximately 0.5g of 95% pure, soluble and active PG-CNP37 peptide was produced
      from 1L of culture using this method and may represent a viable means for large
      scale production of other therapeutic peptides.

PMID- 22959862
TI  - Effects of pretreatment on the microbial community and l-lactic acid production
      in vinasse fermentation.
AB  - Microwave-alkali and steam-alkali coupled pretreatments were carried out to
      improve the yield and optical purity of l-lactic acid produced using vinasse
      fermentation. Lactobacillus casei was inoculated into the system to initiate
      fermentation. Polymerase chain reaction denaturing gradient gel electrophoresis
      was used to analyze the microbial community during fermentation with and without
      the pretreatments. The original bacterial genus in vinasse was essentially
      inactivated, whereas L. casei became the dominant genus after 24h of
      fermentation. The system subjected to microwave-alkali coupled pretreatment
      released more reducing sugars and produced more lactic acid (up to 30.32g/L),
      which is twice that without pretreatment. In addition, the proportion of lactic
      acid in the organic acids also increased. The optical purity of the l-lactic acid
      produced under the microwave-alkali coupled pretreatment reached 91%, which is 2%
      higher than that under the steam-alkali coupled pretreatment and 7% higher than
      that under the control conditions. Therefore, the microwave-alkali coupled
      pretreatment is an effective method for the highly efficient bioconversion of
      vinasse into bioenergy.

PMID- 22959863
TI  - Crisis-induced depression, physical activity and dietary intake among young
      adults: evidence from the 9/11 terrorist attacks.
AB  - Using data from the National Longitudinal Study of Adolescent Health, we provide
      evidence that young adults respond to crisis-induced depression by exercising
      less and having breakfast less often. Exogenous variation in the crisis-induced
      depression is obtained through a unique event in our sample period - the 9/11
      terrorist attacks. We compare those who were interviewed just before and just
      after 9/11 and find a significant and sharp increase in the symptoms of
      depression. We also provide evidence that this increase is not a September
      effect, but an effect of the external traumatic event.

PMID- 22959864
TI  - Stir bar sorptive extraction approaches with a home-made portable electric
      stirrer for the analysis of polycyclic aromatic hydrocarbon compounds in
      environmental water.
AB  - In this study, novel off/on-site stir bar sorptive extraction (SBSE) approaches
      with a home-made portable electric stirrer have been developed for the analysis
      of polycyclic aromatic hydrocarbon compounds (PAHs). In these approaches, a
      miniature battery-operated electric stirrer was employed to provide agitation of
      sample solutions instead of the commonly used large size magnetic stirrer powered
      by alternating current in conventional SBSE process, which could extend the SBSE
      technique from the conventional off-site analysis to the on-site sampling. The
      applicability of the designed off/on-site SBSE sampling approaches was evaluated
      by polydimethylsiloxane (PDMS) coating SBSE-high performance liquid
      chromatography-fluorescence detection (HPLC-FLD) analysis of six target PAHs in
      environmental water. The home-made portable electric stirrer is simple, easy-to
      operate, user friendly, low cost, easy-to-be-commercialized, and can be processed
      in direct immersion SBSE, headspace sorptive extraction (HSSE) and continuous
      flow (CF)-SBSE modes. Since the stir bar was fixed onto the portable device by
      magnetic force, it is very convenient to install, remove and replace the stir
      bar, and the coating friction loss which occurred frequently in conventional SBSE
      process could be avoided. The parameters affecting the extraction of six target
      PAHs by the home-made portable SBSE sampling device with different sampling modes
      were studied. Under the optimum extraction conditions, good linearity was
      obtained by all of three SBSE extraction modes with correlation coefficient (R)
      higher than 0.9971. The limits of detection (LODs, S/N=3) were 0.05-3.41 ng L(-1)
      for direct immersion SBSE, 0.03-2.23 ng L(-1) for HSSE and 0.09-3.75 ng L(-1) for
      CF-SBSE, respectively. The proposed portable PDMS-SBSE-HPLC-FLD method was
      applied for the analysis of six target PAHs in East Lake water, and the
      analytical results obtained by on-site SBSE sampling were in good agreement with
      that obtained by off-site SBSE sampling. The accuracy of the developed method was
      evaluated by recovery test and the recoveries for the spiked sample were found to
      be in the range of 87.1-122.8% for off-site CF-SBSE, 88.8-114.3% for on-site
      sampling, and 87.7-123.6% for off-site SBSE, respectively. The developed method
      is one of the most sensitive methods for PAHs determination and the home-designed
      SBSE system is feasible for the field sampling.

PMID- 22959865
TI  - Ultra trace determination of fluorobenzoic acids in tap and reservoir water using
      solid-phase extraction and gas chromatography-mass spectrometry.
AB  - A method for the ultra trace analysis of 21 fluorobenzoic acids (FBAs) via GC-MS
      based on solid-phase extraction (SPE) and derivatization with BF3.MeOH is
      described. All fluorobenzoic acids were enriched and determined simultaneously.
      Solid-phase extraction on hydrophilic-lipophilic-balanced reversed-phase
      cartridges containing a poly(divinylbenzene-co-N-vinylpyrrolidone) polymer
      allowed a 250-fold enrichment of the acids if 100mL sample volume is used with
      extraction efficiencies between 71% and 94%. The method enables the determination
      of fluorobenzoic acid methyl esters (FBAMEs) down to the range of 6-44 ng L(-1)
      combined with a fast and easy sample-preparation (pH-adjusting prior to SPE and
      derivatization within 24 h at 64  degrees C directly in the vial). It uses low
      amounts of chemicals and is adaptable to larger and smaller sample volumes.
      Simultaneous extraction and determination of 21 fluorinated aromatic acids in
      reservoir samples with high salinity confirmed the applicability and
      reproducibility of the method.

PMID- 22959866
TI  - Optimization of in-line fritless solid-phase extraction for capillary
      electrophoresis-mass spectrometry.
AB  - In this study, in-line frit-free solid-phase extraction (SPE) has been studied
      for the preconcentration of analytes prior to analysis by capillary
      electrophoresis-mass spectrometry (CE-MS). The mixed-mode sorbent Oasis HLB was
      selected for the trapping of compounds of different polarity. Using 2-ethylidene
      1,5-dimethyl-3,3-diphenylpirrolidine (EDDP), dihydrocodeine and codeine as test
      compounds, SPE parameters such as the pH of the sample and composition of the
      washing and elution solvent were optimized. Trapping of the analytes was optimal
      at pH 8.0 or higher. For efficient elution of the SPE micro column, 85% of
      methanol in water with 2% (v/v) acetic acid was used, which also prevented
      current break down in subsequent CE analysis. CE resolution of the test compounds
      was highest for background electrolytes (BGEs) with a pH above 8. For optimal
      analysis, samples were 1:1 diluted with carbonate buffer (1M, pH 8.0) prior to
      analysis, BGE was 60mM ammonium acetate buffer (pH 10.0), and the injected sample
      volume was 60 MUl (i.e., 30 capillary volumes). Good recoveries were found: 101%
      for EDDP, 88% for codeine and 90% for dihydrocodeine. Intraday RSDs for migration
      time and peak areas were below 0.56% and 15%, respectively. Peak widths at half
      height obtained with SPE-CE-MS were 12s for EDDP, 3.7s for dihydrocodeine and
      7.4s for codeine, and were comparable to those for CE-MS. LODs were 0.22 pg/ml
      for EDDP, 2.1 pg/ml for dihydrocodeine and 24 pg/ml for codeine. It is concluded
      that the applied fritless in-line preconcentration construct proved to be highly
      useful for improving the sensitivity of CE while maintaining separation.

PMID- 22959867
TI  - Effects of age and chronic kidney disease on regional aortic distensibility: a
      cardiovascular magnetic resonance study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased arterial
      stiffness, an independent predictor of adverse cardiovascular outcome. Effects of
      CKD on regional aortic stiffness are unknown. This study aimed to determine the
      effects of CKD and ageing on regional thoracic aortic distensibility using
      cardiac magnetic resonance (CMR) imaging. METHODS: This was a cross-sectional
      case control study comparing patients with stage II-IV non-diabetic CKD recruited
      from a university hospital with healthy controls. Aortic distensibility was
      measured in triplicate using CMR (1.5 T) at ascending, proximal descending and
      distal descending thoracic aortic levels and calculated using previously
      validated formulae. RESULTS: 189 patients and 40 controls were recruited.
      Distensibility was reduced at all three thoracic aortic levels in CKD patients
      compared to controls (2.8 vs. 4.1 * 10(-3) mmHg(-1); P < 0.0005 for ascending
      aorta). The cohort was divided into tertiles of age and glomerular filtration
      rate (GFR); distensibility decreased with increasing age (P < 0.0005) and
      decreasing GFR (P < 0.02). In univariate analyses age (r = -0.688, P < 0.0005),
      systolic blood pressure (r = -0.183, P = 0.006) and GFR (r = 0.172, P = 0.009)
      all correlated with ascending aortic distensibility. In a multivariate regression
      model age and GFR were independent predictors of aortic distensibility at all
      three levels with 50% of the variation in ascending aortic distensibility
      explained (P < 0.0005). CONCLUSIONS: Patients with early stage chronic kidney
      disease have reduced distensibility along the entire length of the thoracic
      aorta. This worsens with ageing and as kidney function declines, emphasizing the
      importance of early treatment whilst kidney function is still relatively
      preserved.

PMID- 22959868
TI  - Pleuro-pericarditis, vasculitis, subendocardial and nodular biventricular
      fibrosis. The multiple faces of systemic sclerosis detected by cardiac magnetic
      resonance in the same patient.

PMID- 22959869
TI  - Coronary artery calcium scoring: Influence of adaptive statistical iterative
      reconstruction using 64-MDCT.
AB  - OBJECTIVE: Assessment of coronary artery calcification is increasingly used for
      cardiovascular risk stratification. We evaluated the reliability of calcium
      scoring results using a novel iterative reconstruction algorithm (ASIR) on a high
      definition 64-slice CT scanner, as such data is lacking. METHODS AND RESULTS: In
      50 consecutive patients Agatston scores, calcium mass and volume score were
      assessed. Comparisons were performed between groups using filtered back
      projection (FBP) and 20-100% ASIR algorithms. Calcium score was measured in the
      coronary arteries, signal and noise were measured in the aortic root and left
      ventricle. In comparison with FBP, use of 20%, 40%, 60%, 80%, and 100% ASIR
      resulted in reduced image noise between groups (7.7%, 18.8%, 27.9%, 39.86%, and
      48.56%, respectively; p<0.001) without difference in signal (p=0.60). With ASIR
      algorithms Agatston coronary calcium scoring significantly decreased compared
      with FBP algorithms (837.3 +/- 130.3; 802.2 +/- 124.9, 771.5 +/- 120.7; 744.7 +/-
      116.8, 724.5 +/- 114.2, and 709.2 +/- 112.3 for 0%, 20%, 40%, 60%, 80%, and 100%
      ASIR, respectively, p<0.001). Volumetric score decreased in a similar manner
      (p<0.001) while calcium mass remained unchanged. Mean effective radiation dose
      was 0.81 +/- 0.08 mSv. CONCLUSION: ASIR results in image noise reduction.
      However, ASIR image reconstruction techniques for HDCT scans decrease Agatston
      coronary calcium scores. Thus, one needs to be aware of significant changes of
      the scoring results caused by different reconstruction methods.

PMID- 22959870
TI  - Antidepressant use before coronary artery bypass surgery is associated with long
      term mortality.
AB  - BACKGROUND: Depression is common in patients with coronary artery disease and is
      associated with increased cardiovascular morbidity and mortality. Previous
      reports on the relationship between antidepressant use before coronary artery
      bypass grafting (CABG) and survival are conflicting. Our aim was to study the
      association between preoperative antidepressant use and survival following CABG.
      METHODS: We identified all patients who underwent primary isolated non-emergent
      CABG in Sweden between 2006 and 2008. We used the SWEDEHEART registry and the
      Swedish National Patient Register to acquire information about baseline
      characteristics, and the national Prescribed Drug Register to obtain data
      regarding exposure, defined as at least one antidepressant prescription dispensed
      before surgery. RESULTS: Of the 10,884 patients identified, 1171 (11%) were
      treated with antidepressants before surgery. Unadjusted 4-year survival was 89%
      in the antidepressant group compared with 92% in the group without antidepressant
      use (p=0.002). After multivariable adjustment, antidepressant use was associated
      with increased mortality (hazard ratio [HR] 1.45; 95% confidence interval [CI]
      1.18-1.77), compared with non-use of antidepressants. Antidepressant use was also
      associated with an increased risk of rehospitalization (HR 1.40; 95% CI 1.19
      1.65) and the composite endpoint rehospitalization or death (HR 1.44; 95% CI 1.26
      1.65). CONCLUSIONS: Among patients who underwent contemporary primary isolated
      CABG on a nonemergency basis in Sweden, there was a strong and statistically
      significant association between antidepressant use prior to surgery and long-term
      survival.

PMID- 22959871
TI  - Improved limb perfusion and neoangiogenesis after intramuscular erythropoietin
      infusion in experimental model of limb ischemia.

PMID- 22959872
TI  - Current and emerging concepts in non-invasive and minimally invasive management
      of spine metastasis.
AB  - To provide a comprehensive review on the presentation, work-up and the management
      of spine metastasis with or without epidural spinal cord compression with focus
      on the roles of surgery and radiotherapy. Emphasis has been laid on the
      technological advances with recent development of stereotactic body radiotherapy
      (SBRT) or radiosurgery (SRS) and minimally invasive surgical approaches like
      kyphoplasty and vertebroplasty.

PMID- 22959873
TI  - Intrinsic ligament and triangular fibrocartilage complex (TFCC) tears of the
      wrist: comparison of isovolumetric 3D-THRIVE sequence MR arthrography and
      conventional MR image at 3 T.
AB  - PURPOSE: The purpose of the study was to validate the diagnostic performance of
      high-resolution isovolumetric magnetic resonance arthrography (MRA) for intrinsic
      ligament and triangular fibrocartilage complex (TFCC) tears of the wrist as
      compared to conventional MR imaging (MRI). MATERIALS AND METHODS: Forty-eight
      patients with traumatic TFCC tears at arthroscopy were enrolled. All patients had
      underwent proton-density- and T2-weighted MRI before arthrography and three
      dimensional T1 high-resolution isovolumetric examination (3D-THRIVE) MRA on a 3-T
      MR. We assessed the presence of scapholunate interosseous ligament
      (SLIL)/lunotriquetral interosseous ligament (LTIL) or TFCC tears using the
      arthroscopy as a gold standard. RESULTS: Arthroscopy revealed 37 TFCC central
      tears, 15 TFCC peripheral tears, 20 SLIL tears and 13 LTIL tears. Sensitivities
      of MRI and MRA were 70.3% and 94.6% for detection of TFCC central tears, 60.0%
      and 93.3% for detection of TFCC peripheral tears, 65.0% and 85.0% for SLIL tears,
      and 61.5% and 84.6% for LTIL tears. The specificity of the MRI was 100% for the
      detection of ligaments and TFCC tears. The specificities of the MRA for detection
      of TFCC central tears, TFCC peripheral tears, SLIL tears and LTIL tears were
      100%, 97%, 96.4% and 100%, respectively. CONCLUSION: Isovolumetric 3D-THRIVE
      wrist MRA provided better results for depiction of intrinsic ligament and TFCC
      tears than wrist MRI.

PMID- 22959874
TI  - Improvement of image quality using BLADE sequences in brain MR imaging.
AB  - The purpose of this study is to compare two types of sequences in brain magnetic
      resonance (MR) examinations of uncooperative and cooperative patients. For each
      group of patients, the pairs of sequences that were compared were two T2-weighted
      (T2-W) fluid attenuated inversion recovery sequences with different k-space
      trajectories (conventional Cartesian and BLADE) and two T2-TSE weighted with
      different k-space trajectories (conventional Cartesian and BLADE). Twenty-three
      consecutive uncooperative patients and 44 cooperative patients, who routinely
      underwent brain MR imaging examination, participated in the study. Both
      qualitative and quantitative analyses were performed based on the signal-to-noise
      ratio, contrast-to-noise ratio (CNR), and relative contrast (ReCon) measures of
      normal anatomic structures. The qualitative analysis was performed by experienced
      radiologists. Also, the presence of motion, other (e.g., Gibbs, susceptibility
      artifacts, phase encoding from vessels) artifacts and pulsatile flow artifacts
      was evaluated. In the uncooperative group of patients, BLADE sequences were
      superior to the corresponding conventional sequences in all the cases.
      Furthermore, the differences were found to be statistically significant in almost
      all the cases. In the cooperative group of patients, BLADE sequences were
      superior to the conventional sequences with the differences of the CNR and ReCon
      values in nine cases being statistically significant. Furthermore, BLADE
      sequences eliminated motion and other artifacts and T2 FLAIR BLADE sequences
      eliminated pulsatile flow artifacts. BLADE sequences (T2-TSE and T2 FLAIR) should
      be used in brain MR examinations of uncooperative patients. In cooperative
      patients, T2-TSE BLADE sequences may be used as part of the routine protocol and
      orbital examinations. T2 FLAIR BLADE sequences may be used optionally in
      examinations of AVM, orbits, haemorrhages, ventricular lesions, lesions in the
      frontal lobe, periventricular lesions, lesions in regions close to artifacts and
      lesions in posterior fossa.

PMID- 22959875
TI  - When the world becomes 'too real': a Bayesian explanation of autistic perception.
AB  - Perceptual experience is influenced both by incoming sensory information and
      prior knowledge about the world, a concept recently formalised within Bayesian
      decision theory. We propose that Bayesian models can be applied to autism - a
      neurodevelopmental condition with atypicalities in sensation and perception - to
      pinpoint fundamental differences in perceptual mechanisms. We suggest
      specifically that attenuated Bayesian priors - 'hypo-priors' - may be responsible
      for the unique perceptual experience of autistic people, leading to a tendency to
      perceive the world more accurately rather than modulated by prior experience. In
      this account, we consider how hypo-priors might explain key features of autism -
      the broad range of sensory and other non-social atypicalities--in addition to the
      phenomenological differences in autistic perception.

PMID- 22959876
TI  - Tongue actinomycetoma due to Actinomadura madurae: a rare clinical presentation.
AB  - A 60-year-old male farmer presented with tongue swelling of 1-month duration.
      Local oral clinical examinations showed a painless firm mass in the anterolateral
      aspect of the anterior third of the tongue. Fine needle aspiration for cytology
      confirmed the diagnosis of tongue actinomycetoma due to Actinomadura madurae. The
      patient underwent wide local excision under general anesthesia and had an
      uneventful postoperative recovery. He was started on amikacin sulfate 15 mg/kg
      daily and cotrimoxazole 15 mg/kg twice per day for 6 months. The lesion healed
      completely, with no evidence of recurrence at 6-month follow-up. The route of
      infection in this patient is unclear; however, direct traumatic inoculation is
      the most likely route. To the authors' knowledge, this is the first report of
      tongue mycetoma in the medical literature.

PMID- 22959877
TI  - Primary spindle cell carcinoma of the frontal sinus.

PMID- 22959878
TI  - Volume changes of iliac crest autogenous bone grafts after vertical and
      horizontal alveolar ridge augmentation of atrophic maxillas and mandibles: a 6
      year computerized tomographic follow-up.
AB  - PURPOSE: To evaluate by computerized tomography the long-term volume resorption
      of autogenous corticocancellous grafted bone harvested from the ilium and used in
      an alveolar augmentation procedure followed by endosseous dental implant
      placement. PATIENTS AND METHODS: Eleven maxillary grafts (8 positioned
      horizontally) and 13 mandibular grafts (10 positioned vertically) were placed in
      16 patients. Using software programs, pre- and postsurgical computerized
      tomographic scans were used to compare volumes of grafts over time (up to 6 yr)
      to determine the annual percentage of remaining bone and the overall percentage
      of bone resorption that could be expected. Yearly measurements of volumes and
      percentages of remaining bone were then compared statistically. RESULTS: At the 6
      year survey for blocks grafted in the mandible, an average resorption rate of 87%
      was obtained; for maxillary grafts at the same survey, complete resorption of the
      grafts (mean, 105.5%) was recorded. In general, bone resorption appeared slow,
      except for that recorded in the first 2 years of healing, the only period in
      which statistical comparisons among all time points showed significant
      differences for all variables. CONCLUSIONS: Volumetric measurements of the grafts
      and their related percentages of remaining bone attested to a progressive and
      unavoidable bone resorption of almost all the grafted bone in the maxilla and
      mandible. Although the present data were from a heterogeneous group of defects
      treated with horizontal and vertical procedures, clinicians, when performing
      alveolar bone augmentation with an autogenous hip bone, should aim at titanium
      dental implant osseointegration, not only in the augmented bone but also in the
      native bone below the graft.

PMID- 22959879
TI  - Open reduction and internal fixation of mandibular angle fractures: does the
      transbuccal technique produce fewer complications after treatment than the
      transoral technique?
AB  - PURPOSE: The study's purpose was to answer the following clinical question: in
      patients with mandibular angle fractures requiring open reduction and internal
      fixation, do those who have fixation screws inserted using a transbuccal approach
      compared with those with fixation screws inserted using a transoral approach have
      fewer complications after treatment? The investigators hypothesized that the
      transoral approach was associated with a higher risk of complications. MATERIALS
      AND METHODS: A multicenter retrospective cohort study was performed in patients
      who had open reduction and internal fixation of mandibular angle fractures from
      2008 to 2010 within Western Australia. Patients were divided into transbuccal and
      transoral groups and then further subdivided into groups with and without
      fixation failures (primary outcome variable) and statistically compared. Binary
      logistic regression was used to control for possible confounders, which included
      patient gender, age, a wisdom tooth within the fracture not extracted, dental
      caries, partial dentition, bilateral/unilateral fractures, and smoking. RESULTS:
      In total 597 patients were in the study. Sixteen percent of patients in the
      transoral group had complications after treatment versus 10% in the transbuccal
      group. For the transoral technique, the odds of having fixation failure was 1.71
      times greater than with the transbuccal technique (95% confidence interval, 1.02
      to 2.93; P = .04). Incidences of all complication variables (hardware
      loosening/fracturing, wound dehiscence, secondary infection, surgery redo,
      nonunion/malunion of fracture, and removal of plate) were lower in the
      transbuccal group apart from plate fracture. CONCLUSION: The transbuccal
      technique was associated with fewer complications after treatment compared with
      the transoral technique.

PMID- 22959880
TI  - Treatment of microsporidial keratoconjunctivitis with repeated corneal swabbing.
AB  - PURPOSE: To report the effect of repeated corneal swabbing in patients with
      microsporidial keratoconjunctivitis. DESIGN: Retrospective noncomparative case
      series. METHODS: Sixteen eyes of 14 healthy patients with microsporidial
      keratoconjunctivitis were diagnosed based on the detection of microsporidia in
      corneal scrapings using Gram stain, the modified Kinyoun acid-fast stain, or
      both. Polymerase chain reaction plus gene analysis of the microsporidian 16S
      ribosomal RNA had been performed in 10 patients who sought treatment between 2010
      and 2011. Some of the lesions were scraped for procurement of specimens. The
      remaining lesions were wiped off gently by cotton swabs. Repeated swabbing was
      performed if infection persisted or new lesions were observed at follow-up. To
      prevent secondary bacterial infection, 0.3% norfloxacin or 0.25 % chloramphenicol
      were prescribed. RESULTS: The mean age was 52.2 years. All patients had the
      characteristic disseminated, punctate, slightly elevated, white epithelial
      lesions. The denser white lesions could be removed easily after gentle swabbing,
      and most epithelium remained intact. The 10 cases with positive polymerase chain
      reaction results were all identified to be Vittaforma corneae. The mean number of
      corneal swabbing was 3.3, and the mean disease resolution time was 6.6 days. No
      patients had recurrence or loss of visual acuity at last follow-up. CONCLUSIONS:
      Repeated swabbing effectively can eradicate corneal epithelial microsporidial
      lesions in approximately 1 week. It is easy to perform, less painful, and more
      acceptable for the patients.

PMID- 22959882
TI  - Binocular visual acuity in intermittent exotropia: role of accommodative
      convergence.
AB  - PURPOSE: To investigate binocular interaction of visual acuity (VA) in patients
      with intermittent exotropia and its relationship with accommodative responses
      during binocular vision. DESIGN: Prospective pilot study. METHODS: setting:
      Institutional. patient: Sixty-three patients with intermittent exotropia between
      8 and 15 years of age. observation: Binocular VA and monocular VA were measured
      in sequence. Accommodative responses of both eyes were measured using the WAM
      5500 autorefractor/keratometer (GrandSeiko) during binocular and monocular
      viewing conditions at 6 m. Accommodative responses during binocular vision were
      calculated using the difference between the refractive errors of binocular and
      monocular vision. main outcome measures: Binocular interactions of VA were
      categorized as binocular summation, equivalency, or inhibition. The prevalence of
      the 3 patterns of binocular interaction was investigated. Accommodative responses
      were correlated with differences between binocular VA and better monocular VA.
      RESULTS: Most patients (38 patients; 60.3%) showed binocular equivalency.
      Binocular summation and inhibition were noted in 19 (30.2%) and 6 (9.5%)
      patients, respectively. Linear regression analysis revealed a significant
      correlation between binocular interaction and accommodative responses during
      binocular vision (P < .001). Accommodative responses significantly correlated
      with the size of exodeviation at distance (P = .010). CONCLUSIONS: In patients
      with intermittent exotropia, binocular interaction is associated with
      accommodative response during binocular vision and the size of exodeviation,
      suggesting that accommodative convergence is a mechanism that maintains ocular
      alignment. Therefore, binocular interaction, especially binocular inhibition, can
      be a good indicator of diminishing fusional control in intermittent exotropia.

PMID- 22959881
TI  - Nocardia keratitis: clinical course and effect of corticosteroids.
AB  - PURPOSE: To compare the clinical course of Nocardia species keratitis with
      keratitis resulting from other bacterial organisms and to assess the effect of
      corticosteroids as adjunctive therapy using data collected from the Steroids for
      Corneal Ulcers Trial. DESIGN: Subgroup analysis of a randomized controlled trial.
      METHODS: setting: Multicenter randomized controlled trial. study population: Five
      hundred patients with bacterial keratitis randomized 1:1 to topical
      corticosteroid or placebo who had received at least 48 hours of topical
      moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate
      1% or placebo and clinical course of Nocardia keratitis. main outcome measures:
      Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months
      from enrollment. RESULTS: Of 500 patients enrolled in the trial, 55 (11%) had a
      Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation
      visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity,
      20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity
      (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines
      less of improvement in visual acuity compared with non-Nocardia ulcers (0.21
      logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to
      0.33 logarithm of the minimal angle of resolution; P = .001). This difference may
      reflect the better starting visual acuity in patients with Nocardia ulcers. In
      Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase
      in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P =
      .03). CONCLUSIONS: Nocardia ulcers responded well to treatment. They showed less
      overall improvement in visual acuity than non-Nocardia ulcers, but had better
      presentation acuity. Corticosteroids may be associated with worse outcomes.

PMID- 22959883
TI  - Alteration of autophagosomal proteins in the brain of multiple system atrophy.
AB  - Autophagosomal formation is an initial step for macroautophagy. Similar to the
      yeast autophagy-related gene 8 (ATG8), mammalian ATG8 is responsible for
      autophagosomal formation, and categorized into LC3 and GABARAPs/GATE-16. Recent
      studies have shown that impairment of the autophagy-lysosome system is associated
      with formation of cytoplasmic inclusions observed in various neurodegenerative
      disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
      Although abnormal alpha-synuclein accumulation is a cardinal neuropathological
      feature in PD, DLB and multiple system atrophy (MSA), it is unclear whether
      autophagy is altered in MSA. We here demonstrated that the level of matured
      GABARAPs was significantly decreased in the cerebellum of MSA relative to
      controls, and that the higher levels of matured and lipidated LC3 were detected
      in detergent-insoluble fraction of MSA. Immunohistochemical analysis showed that
      the vast majority of glial cytoplasmic inclusions, a hallmark of MSA, were
      positive for LC3, whereas they were unstained or barely stained with anti
      GABARAPs or anti-GATE-16 antibodies. Our data suggest that autophagy maturation
      is impaired through the repressed levels of autophagosomal proteins in MSA. 

PMID- 22959884
TI  - Comparing new anticoagulants in atrial fibrillation using the number needed to
      treat.

PMID- 22959885
TI  - Alpha 2A-adrenoreceptor blockade improves sepsis-induced acute lung injury
      accompanied with depressed high mobility group box-1 levels in rats.
AB  - PURPOSE: To investigate the effects of alpha2A-adrenoreceptor blockade on acute
      lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a
      rat model of sepsis. METHODS: Sepsis was induced in male rats by cecal ligation
      and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized
      to the Sham group, the CLP group, and the CLP+maleate group. Five hours after
      CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same
      volume of vehicle. Serum levels of TNF-alpha, IL-6, IL-10, HMGB1, and
      norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF
      alpha, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1,
      nuclear factor (NF)-kappaB activation, myeloperoxidase (MPO) activity,
      histological scores, and wet-to-dry weight ratio were determined 24h after CLP.
      In additional CLP and CLP+maleate groups, the 7 day survival rate was evaluated.
      RESULTS: Compared with the CLP group, serum TNF-alpha at 6h, HMGB1 at 18 and 24h,
      and norepinephrine at 6 and 18 h after CLP decreased in the CLP+maleate group.
      Lung TNF-alpha, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-kappaB
      activation, MPO activity, histological scores, and wet-to-dry weight ratio were
      lower in the CLP+maleate group than the CLP group. There was no significant
      difference in 7 day survival rate between the CLP and CLP+maleate groups.
      CONCLUSIONS: The alpha2A-adrenoreceptor blockade by a specific antagonist maleate
      improves sepsis-induced acute lung injury accompanied with depressed HMGB1
      expression in rats. The mechanism seemed to be mediated partly through
      downregulation of the signal transductions of the NF-kappaB pathway.

PMID- 22959886
TI  - The effect of dietary walnuts compared to fatty fish on eicosanoids, cytokines,
      soluble endothelial adhesion molecules and lymphocyte subsets: a randomized,
      controlled crossover trial.
AB  - We tested the hypothesis that walnut consumption can exert effects on markers of
      inflammation and endothelial activation similar to those produced by fish
      consumption. In a crossover dietary intervention trial, 25 normal to mildly
      hyperlipidemic men and women were randomly assigned to one of three isoenergetic
      diets: a walnut diet incorporating 42.5 g of walnuts per 10.1 mJ 6 times per week
      (1.8% of energy n-3 fat); a fish diet providing 113 g of fatty fish per 10.1 mJ 2
      times per week (0.8% of energy n-3 fat), or a control diet (no nuts or fish, 0.4%
      of energy n-3 fat) for 4 weeks on each diet. Both the walnut and fish diets
      inhibited circulating concentrations of prostaglandin E metabolite (PGEM) and 11
      dehydro thromboxane B2, but demonstrated no effect on blood interleukin-1beta (IL
      1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha- (TNF-alpha-), and C
      reactive protein (CRP) or the number of circulating lymphocyte subsets. On the
      walnut diet the proportion of plasma phospholipid alpha--linolenic acid (ALA)
      increased 140% and arachidonic acid (AA) decreased 7% compared to both the
      control and fish diets. The proportion of plasma phospholipid eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) increased about 200% and 900%
      respectively on the fish diet relative to either the control or walnut diet. The
      walnut diet inhibited E-selectin by 12.7% relative to the fish diet, and the fish
      diet inhibited secretory intercellular adhesion molecule-1 (s-ICAM-1) by 4.5%
      relative to the control diet. Both walnuts and fish in commonly consumed amounts
      may have modest albeit distinct effects on circulating adhesion molecules.

PMID- 22959888
TI  - Effects of experimentally induced dissociation on attention and memory.
AB  - Dissociation is an important aspect of responses to traumatic events. According
      to a number of influential theories, it negatively impacts cognitive performance
      including encoding of the trauma memories, leading to an increased risk of later
      conditions such as posttraumatic stress disorder (PTSD). We tested this
      hypothesis experimentally in two studies by inducing dissociation in the
      laboratory and investigating the effects on several aspects of cognition,
      including time estimation, digit and spatial span, and story recall. Dissociation
      was related to decrements in time estimation, digit span, and story retention,
      but did not affect perceptual attention, spatial span, or immediate story recall.
      The results are discussed in the context of theoretical models of PTSD and their
      implications for official questioning of traumatized individuals such as sexual
      assault survivors.

PMID- 22959887
TI  - Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with
      cannabinoid-independent function.
AB  - Docosahexaenoylethanolamide, the structural analog of the endogenous cannabinoid
      receptor ligand anandamide, is synthesized from docosahexaenoic acid (DHA) in the
      brain. Although docosahexaenoylethanolamide binds weakly to cannabinoid
      receptors, it stimulates neurite growth, synaptogenesis and glutamatergic
      synaptic activity in developing hippocampal neurons at concentrations of 10-100
      nM. We have previously proposed the term synaptamide for
      docosahexaenoylethanolamide to emphasize its potent synaptogenic activity and
      structural similarity to anandamide. Synaptamide is subjected to hydrolysis by
      fatty acid amide hydrolase, and can be oxygenated to bioactive metabolites. The
      brain synaptamide content is dependent on the dietary DHA intake, suggesting an
      endogenous mechanism whereby diets containing adequate amounts of omega-3 fatty
      acids improve synaptogenesis in addition to well-recognized anti-inflammatory
      effects.

PMID- 22959889
TI  - [Malnutrition screening in clinical practice].
AB  - Protein energy malnutrition (PEM) occurs when energy and protein intake do not
      meet requirements. It has a functional and structural impact and increases both
      morbidity and mortality of a given disease. The Nutrition Committee of the French
      Pediatric Society recommends weighing and measuring any child when hospitalized
      or seen in consultation. The body mass index (BMI) must be calculated and
      analyzed according to references any time growth kinetics cannot be analyzed. Any
      child with a BMI below the third centile or -2 standard deviations for age and
      sex needs to be examined looking for clinical signs of malnutrition and signs
      orienting toward an etiology and requires having his BMI and height dynamics
      plotted on a chart. PEM warrants drawing up a nutritional strategy along with the
      overall care plan. A target weight needs to be determined as well as the
      quantitative and qualitative nutritional care including its implementation. This
      plan must be evaluated afterwards in order to adapt the nutritional therapy.

PMID- 22959890
TI  - Mental health and somatic symptom severity are associated with reduced physical
      activity among US Iraq and Afghanistan veterans.
AB  - OBJECTIVE: Ensuring that Iraq and Afghanistan veterans engage in adequate
      physical activity is essential to prevent metabolic and cardiovascular diseases,
      and promote psychological well-being. Identifying factors associated with
      physical activity in this population will yield areas for targeted interventions
      aimed at increasing activity. METHOD: Correlates of meeting physical activity
      recommendations (>= 150 min/week of moderate-to-vigorous physical activity
      [MVPA]) were examined in Iraq/Afghanistan veterans assessed at intake to VA Puget
      Sound Healthcare System's post-deployment health clinic (May, 2005-August, 2009;
      N=266). RESULTS: The majority were male (94.3%) and Caucasian (70.7%), with an
      average age of 29.8 (SD=7.3) years. Participants engaged in a median of 180
      weekly MVPA minutes. Among those meeting (59%) and not meeting (41%)
      recommendations, median weekly MVPA minutes were 540 and 0, respectively. In
      multivariate regression models, higher levels of depression (p=.042) and somatic
      (p=.018) symptom severity were associated with significantly decreased odds of
      meeting physical activity recommendations. CONCLUSION: Overall, physical activity
      engagement among Iraq/Afghanistan veteran VA patients was above the level
      specified in national recommendations. Those with higher depressive and somatic
      symptoms were less likely to meet physical activity recommendations and may
      benefit from targeted physical activity promotion interventions.

PMID- 22959892
TI  - Kinetics and mechanism of electrochemical oxygen reduction using
      platinum/clay/Nafion catalyst layer for polymer electrolyte membrane fuel cells.
AB  - This work demonstrates the use of amino functionalized Mg-phyllosilicate
      clay/Nafion nanocomposite film embedded with Pt nanoparticles (Pt/AC/N) for
      catalyzing oxygen reduction reaction (ORR) in sulphuric acid medium. Pt/AC/N
      nanocomposite films were surface characterized using transmission electron
      microscope. Cyclic and linear scan voltammetry studies were carried out under
      hydrodynamic conditions taking rotating-ring disc electrode (RRDE) as the working
      electrode. The effects of clay content, Pt mass loading, electrode rotation rate,
      and temperature on the ORR kinetics were studied. The Tafel slopes were found to
      vary between 118 and 126 mV dec(-1) indicating a good ORR kinetics. The exchange
      current density values calculated after mass transfer correction ranged from
      5.8*10(-7) to 2.4*10(-6) A cm(-2). From the RRDE disc currents, Koutecky-Levich
      plots were constructed and the ORR mechanism was found to follow a four electron
      path with minimum H(2)O(2) formation of ~1.6%. The effect of temperature on ORR
      kinetics was found at 25, 40, and 50 degrees C. The energy of activation
      calculated to be 7.68 kJ mol(-1) and comparable to the standard Pt/C catalyzed
      ORR systems.

PMID- 22959891
TI  - Effects of ethanol, Delta(9)-tetrahydrocannabinol, or their combination on object
      recognition memory and object preference in adolescent and adult male rats.
AB  - Recent advances have been made in our understanding of the deleterious effects of
      both ethanol and THC on adolescent behavior and brain development. However, very
      little is known about the combined effects of EtOH+THC during adolescence, a time
      in which these drugs are often used together. The purpose of this experiment was
      to: (1) determine whether EtOH and/or THC induced greater working memory
      impairment in adolescent than adult male rats using the novel object recognition
      (NOR) task and (2) determine whether the EtOH+THC combination would produce a
      more potent additive effect in adolescents than adults when compared to these
      drugs alone. NOR was performed with a 24h delay under each of the four drug
      conditions: vehicle; 1.5g/kg ethanol; 1.0mg/kg THC; and 1.5g/kg EtOH+1.0mg/kg
      THC, at 72h intervals. The results show that there was an age effect on working
      memory in NOR after the EtOH+THC challenge. Specifically, adolescent animals
      showed a preference for the familiar object whereas adults showed no preference
      for the novel or familiar object, the latter being characteristic of a classic
      working memory deficit. These effects were not dependent on changes in
      exploration across session, global activity across drug condition, or total
      object exploration. These novel findings clearly indicate that further
      understanding of this age-drug interaction is crucial to elucidating the
      influence that adolescent EtOH+THC use may have on repeated drug use and abuse
      later in life.

PMID- 22959893
TI  - The neuronal ceroid-lipofuscinoses: a historical introduction.
AB  - The neuronal ceroid-lipofuscinoses (Batten disease) collectively constitute one
      of the most common groups of inherited childhood onset neurodegenerative
      disorders, and have also been identified in many domestic and laboratory animals.
      The group of human neuronal ceroid-lipofuscinoses currently comprises 14
      genetically distinct disorders, mostly characterised by progressive mental, motor
      and visual deterioration with onset in childhood or adolescence. Abnormal
      autofluorescent, electron-dense granules accumulate in the cytoplasm of nerve
      cells, and this storage process is associated with selective destruction and loss
      of neurons in the brain and retina. The present paper outlines nearly 200 years
      of clinical, neuropathological, biochemical and molecular genetic research,
      gradually leading, since 1995, to the identification of 13 different genes and
      over 360 mutations that underlie these devastating brain disorders and form the
      basis of a new classification system. These genes are evidently of vital
      importance for the normal development and maintenance of cerebral neurons.
      Elucidation of their functions and interactions in health and disease is a
      prerequisite for the identification of possible therapeutic targets, but may also
      further our understanding of the basic mechanisms of neurodegeneration and
      ageing. An account is also given of the development of international cooperation
      and free access electronic resources facilitating NCL research. This article is
      part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten
      Disease.

PMID- 22959895
TI  - Feglymycin, a unique natural bacterial antibiotic peptide, inhibits HIV entry by
      targeting the viral envelope protein gp120.
AB  - Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently
      inhibits HIV replication in the lower MUM range. FGM also inhibits HIV cell-to
      cell transfer between HIV-infected T cells and uninfected CD4(+) T cells and the
      DC-SIGN-mediated viral transfer to CD4(+) T cells. FGM potently interacts with
      gp120 (X4 and R5) as determined by SPR analysis and shown to act as a gp120/CD4
      binding inhibitor. Alanine-scan analysis showed an important role for l-aspartic
      acid at position 13 for its anti-HIV activity. In vitro generated FGM-resistant
      HIV-1 IIIB virus (HIV-1 IIIB(FGMres)) showed two unique mutations in gp120 at
      positions I153L and K457I. HIV-1 IIIB(FGMres) virus was equally susceptible to
      other viral binding/adsorption inhibitors with the exception of dextran sulfate
      (9-fold resistance) and cyclotriazadisulfonamide (>15-fold), two well-described
      compounds that interfere with HIV entry. In conclusion, FGM is a unique prototype
      lead peptide with potential for further development of more potent anti-HIV
      derivatives.

PMID- 22959894
TI  - Human parainfluenza virus serotypes differ in their kinetics of replication and
      cytokine secretion in human tracheobronchial airway epithelium.
AB  - Human parainfluenza viruses (PIVs) cause acute respiratory illness in children,
      the elderly, and immunocompromised patients. PIV3 is a common cause of
      bronchiolitis and pneumonia, whereas PIV1 and 2 are frequent causes of upper
      respiratory tract illness and croup. To assess how PIV1, 2, and 3 differ with
      regard to replication and induction of type I interferons, interleukin-6, and
      relevant chemokines, we infected primary human airway epithelium (HAE) cultures
      from the same tissue donors and examined replication kinetics and cytokine
      secretion. PIV1 replicated to high titer yet did not induce cytokine secretion
      until late in infection, while PIV2 replicated less efficiently but induced an
      early cytokine peak. PIV3 replicated to high titer but induced a slower rise in
      cytokine secretion. The T cell chemoattractants CXCL10 and CXCL11 were the most
      abundant chemokines induced. Differences in replication and cytokine secretion
      might explain some of the differences in PIV serotype-specific pathogenesis and
      epidemiology.

PMID- 22959896
TI  - The physics of tissue formation with mesenchymal stem cells.
AB  - Cells react to various forms of physical phenomena that promote and maintain the
      formation of tissues. The best example of this are cells of musculoskeletal
      origin, such as mesenchymal stem cells (MSCs), which consistently proliferate or
      differentiate under cues from hydrostatic pressure, diffusive mass transport,
      shear stress, surface chemistry, mechanotransduction, and molecular kinetics. To
      date, no other cell type shows greater receptiveness to macroscopic and
      microscopic cues, highlighting the acute sensitivity of MSCs and the importance
      of physical principles in tissue homeostasis. In this review, we describe the
      literature that has shown how physical phenomena govern MSCs biology and provide
      insight into the mechanisms and strategies that can spur new biotechnological
      applications with tissue biology.

PMID- 22959897
TI  - [Quality of life after laparoscopic radical hysterectomy for cervical cancer:
      study of 22 cases].
AB  - OBJECTIVE: Laparoscopic radical hysterectomy is currently the surgical treatment
      of cervical cancer. The objective of this study was to evaluate the quality of
      life of patients with cervical cancer treated by radical hysterectomy by
      laparoscopy. PATIENTS AND METHODS: Quality of life was evaluated in 22 patients
      with cervical cancer (FIGO stade IB1-IIB) treated by laparoscopic radical
      hysterectomy. The study employed two types of survey questionnaires: EORTC QLQ-C
      30 and QLQ-OV 28. RESULTS: After a median follow-up of 25 months (range: 12-48
      months), the average global health scores and quality of life after the surgery
      was high, indicating a good overall quality of life. The symptoms most commonly
      implicated were fatigue and insomnia. The average symptom scores (abdominal,
      peripheral neuropathy, side effects of chemotherapy) was low, meaning little
      inconvenience. It noted, however, an exception for the symptoms of menopause that
      generate significant discomfort in several patients. Among patients with a
      regular sexual activity, most described a change in frequency and quality of
      reporting. DISCUSSION AND CONCLUSIONS: Patients with cervical cancer treated by
      laparoscopy have good overall quality of life. The function that is most affected
      by the treatment in the majority of patients is sexual function. A comparative
      prospective study with laparotomy would be necessary.

PMID- 22959898
TI  - Soil salinity decreases global soil organic carbon stocks.
AB  - Saline soils cover 3.1% (397 million hectare) of the total land area of the
      world. The stock of soil organic carbon (SOC) reflects the balance between carbon
      (C) inputs from plants, and losses through decomposition, leaching and erosion.
      Soil salinity decreases plant productivity and hence C inputs to the soil, but
      also microbial activity and therefore SOC decomposition rates. Using a modified
      Rothamsted Carbon model (RothC) with a newly introduced salinity decomposition
      rate modifier and a plant input modifier we estimate that, historically, world
      soils that are currently saline have lost an average of 3.47 tSOC ha(-1) since
      they became saline. With the extent of saline soils predicted to increase in the
      future, our modelling suggests that world soils may lose 6.8 Pg SOC due to
      salinity by the year 2100. Our findings suggest that current models overestimate
      future global SOC stocks and underestimate net CO2 emissions from the soil-plant
      system by not taking salinity effects into account. From the perspective of
      enhancing soil C stocks, however, given the lower SOC decomposition rate in
      saline soils, salt tolerant plants could be used to sequester C in salt-affected
      areas.

PMID- 22959899
TI  - Dietary exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans via fish
      consumption and dioxin-like activity in fish determined by H4IIE-luc bioassay.
AB  - Dietary exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      via fish consumption in two major electronic (e) waste sites: Guiyu (GY),
      Guangdong Province and Taizhou (TZ), Zhejiang Province, and dioxin-like activity
      in fish determined by H4IIE-luc bioassay. In the present study, all fish were
      below EU's maximum allowable concentration in muscle of fish (4 pg WHO-TEQ/g wet
      wt), except crucian (4.28 pg WHO-TEQ/g wet wt) and silver carps (7.49 pg WHO
      TEQ/g wet wt) collected from GY rivers. Moreover, the residual concentration in
      bighead carp collected from GY (2.15 pg WHO-TEQ/g wet wt) was close to the EU's
      action level (3 pg WHO-TEQ/g wet wt) which gives "early warning" to the competent
      authorities and operators to take measures to eliminate contamination. In
      addition, results indicated that the maximum human intake of PCDD/Fs via
      freshwater fish consumption in GY was 4.31 pg WHO-TEQ/kg bw/day, which exceeds
      the higher end of the tolerable daily intake recommended by the WHO, EC-SCF and
      JECFA (1-4, 2 and 2.3 pg WHO-TEQ/kg bw/day respectively). Furthermore, H4IIE-luc
      cell bioassay provides a very sensitive and cost-efficient screening tool for
      assessing the overall dioxin-like toxicity in the study, and is therefore
      valuable for high-throughput environmental monitoring studies.

PMID- 22959901
TI  - Association of body mass index with removal of etonogestrel subdermal implant.
AB  - BACKGROUND: Bleeding irregularities represent the most common etonogestrel
      subdermal implant (ESI) removal indication. STUDY DESIGN: ESI placements (n=304)
      from June 2007 to April 2011 were grouped by removal indications. Group
      characteristics were compared using one-way analysis of variance, Kruskal-Wallis
      and chi(2) test. RESULTS: Of 304 insertions, 30.6% reported irregular bleeding.
      Removal indications included bleeding (Group 1, n=50), side effects (Group 2,
      n=17) and desired pregnancy/no need (Group 3, n=25). Group 4 kept (n=198) or
      reinserted (n=14) ESI. Median body mass index was lower for Group 1 compared to
      other groups (p=.012). Group 3 was older than Group 1 or 4 (p=.021), and more
      likely parous (p<.001) and postpartum (p=.001) than other groups. Lactational
      placement was more common in Group 3 than 4 (p<.001). Obese women were 2.6 times
      less likely to remove ESI for bleeding vs. normal-weight or overweight women (95%
      confidence interval, 1.2-5.7; p=.014). CONCLUSIONS: After adjusting for age and
      parity, obese women were less likely to have ESI removal for bleeding.

PMID- 22959902
TI  - Transvaginal administration of intraamniotic digoxin prior to dilation and
      evacuation.
AB  - BACKGROUND: Transabdominal injection of digoxin into the amniotic fluid or fetus
      to induce fetal demise before dilation and evacuation (D&E) abortion has become
      common practice since the passage of the Partial-Birth Abortion Ban Act in 2007.
      STUDY DESIGN: We performed a prospective study to assess the feasibility of
      transvaginal administration of intraamniotic digoxin the day before D&E. All
      women between 18 0/7 and 23 5/7 weeks of gestation seeking termination from
      December 2009 to May 2011 were approached for study participation. Women who
      declined participation were asked to identify their primary rationale. For women
      declining study participation, transection of the umbilical cord during D&E was
      performed to meet the requirements of the ban. RESULTS: Over 18 months, 134 women
      met study entry criteria and 108 (81%) declined to participate. Of the 26 women
      who enrolled, 1.0 mg undiluted digoxin was successfully administered
      transvaginally in 24 (92%, 95% confidence interval 75%-99%). The most common
      reasons for declining participation were discomfort with preoperatively inducing
      fetal demise (37%) and desire to avoid a medically unnecessary medication (36%).
      CONCLUSIONS: Transvaginal administration of digoxin is a feasible alternative to
      transabdominal administration to induce preoperative fetal demise. The majority
      of women decline digoxin administration when an alternative is available.

PMID- 22959903
TI  - The Supreme Court rules, and it's both good and bad news for reproductive health.

PMID- 22959904
TI  - Burden of unintended pregnancy in the United States: potential savings with
      increased use of long-acting reversible contraception.
AB  - BACKGROUND: This study evaluated the total costs of unintended pregnancy (UP) in
      the United States (US) from a third-party health care payer perspective and
      explored the potential role for long-acting reversible contraception (LARC) in
      reducing UP and resulting health care expenditure. STUDY DESIGN: An economic
      model was constructed to estimate direct costs of UP as well as the proportion of
      UP costs that could be attributed to imperfect contraceptive adherence. The model
      considered all women requiring reversible contraception in the US: the pattern of
      contraceptive use and the rates of UP were derived from published sources. The
      costs of UP in the United States and the proportion of total cost that might be
      avoided by improved adherence through increased use of LARC were estimated.
      RESULTS: Annual medical costs of UP in the United States were estimated to be
      $4.6 billion, and 53% of these were attributed to imperfect contraceptive
      adherence. If 10% of women aged 20-29 years switched from oral contraception to
      LARC, total costs would be reduced by $288 million per year. CONCLUSIONS:
      Imperfect contraceptive adherence leads to substantial UP and high, avoidable
      costs. Improved uptake of LARC may generate health care cost savings by reducing
      contraceptive non-adherence.

PMID- 22959905
TI  - Effect of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) on serum
      androgen markers in normal-weight, obese, and extremely obese women.
AB  - BACKGROUND: The effects of subcutaneous depo-medroxyprogesterone acetate (DMPA
      SC) injection on androgenic markers in obese women have not previously been
      studied. STUDY DESIGN: Five normal-weight [body mass index (BMI)=18.5-24.9
      kg/m2], five obese (BMI=30-39.9 kg/m2) and five extremely obese (BMI>=40 kg/m2)
      women were recruited for this prospective experimental study in which 104 mg DMPA
      SC was administered at baseline and 12 weeks later. Serum levels of total
      testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS),
      3alpha-androstanediol glucuronide and sex hormone-binding globulin (SHBG) were
      quantified by immunoassay methods at baseline and at 13 and 26 weeks following
      the first injection; free T was calculated. RESULTS: At baseline, obese women had
      lower levels of A and SHBG and higher total and free T levels than normal-weight
      women. There were a statistically significant decrease in the levels from
      baseline to week 26 among all three BMI classes for A, total T and SHBG (p<=.03)
      and an increase from baseline to week 26 in weight (p=.02). In addition, there
      was a statistically significant decrease in DHEAS from baseline to week 13 among
      all three BMI classes (p=.01), which was not sustained at week 26 (p>.1).
      Overall, the three groups responded similarly to all changes at week 13, and
      there were no statistically significant differences between groups at any time
      point (p>=.06). CONCLUSION: DMPA-SC use in normal-weight, obese and extremely
      obese women can decrease serum androgen markers.

PMID- 22959906
TI  - Levonorgestrel-releasing intrauterine system for heavy menstrual bleeding
      improves hemoglobin and ferritin levels.
AB  - BACKGROUND: We compared the effects of the levonorgestrel-releasing intrauterine
      system (LNG-IUS) with cyclic oral medroxyprogesterone acetate (MPA) on hemoglobin
      and serum ferritin levels in women with heavy menstrual bleeding (HMB). STUDY
      DESIGN: This was a multicenter, randomized study assessing the efficacy of the
      LNG-IUS and oral MPA (10 mg/day for 10 days) in women with confirmed HMB over 6
      cycles of treatment. We previously reported that treatment with the LNG-IUS
      resulted in greater menstrual blood loss reduction than MPA. In this analysis,
      hemoglobin and serum ferritin levels were assessed at baseline, Cycle 3, and at
      Cycle 6, and the relative improvement on treatment was subjectively rated by
      investigators and women. RESULTS: One hundred and sixty-five women were
      randomized (82 LNG-IUS/83 MPA). Increases in median hemoglobin levels from
      baseline to Cycle 6 (7.5% vs. 1.9%; p<.001) and median serum ferritin levels
      (68.8% vs. 14.3%; p<.001) were greater in the LNG-IUS group than in the oral MPA
      group. Baseline median hemoglobin and ferritin levels were 12.4 g/dL and 19.0
      mcg/L with the LNG-IUS and 12.2 g/dL and 19.0 mcg/L with oral MPA, respectively.
      At Cycle 6, the corresponding medians were 13.4 g/dL and 34.0 mcg/L with the LNG
      IUS and 12.6 g/dL and 21.0 mcg/L with oral MPA. At Cycle 6, the proportion of
      women who rated their bleeding as 'improved' was higher with the LNG-IUS than
      with oral MPA, both according to investigator assessment (93.6% vs. 61.0%) and
      self-assessment (93.6% vs. 67.1%). CONCLUSIONS: Women treated with the LNG-IUS
      had greater increases in median hemoglobin and serum ferritin levels, and higher
      rates of subjective improvement than women treated with oral MPA.

PMID- 22959907
TI  - Critical role of VEGF-C/VEGFR-3 signaling in innate and adaptive immune responses
      in experimental obliterative bronchiolitis.
AB  - Chronic inflammation, a hallmark of obliterative bronchiolitis, is known to
      induce lymphangiogenesis. We therefore studied the role of lymphangiogenic
      vascular endothelial growth factor C (VEGF-C), its receptor VEGFR-3, and
      lymphangiogenesis during development of experimental obliterative bronchiolitis
      [ie, obliterative airway disease (OAD)] in rat tracheal allografts. The
      functional importance of VEGF-C was investigated by adenovirus-mediated
      overexpression of VEGF-C (AdVEGF-C), and by inhibition of VEGF-C activity with
      VEGFR-3-Ig (AdVEGFR-3-Ig). Analyses included histology, immunohistochemistry, and
      real-time RT-PCR 10 and 30 days after transplantation. In the course of OAD
      development, lymphangiogenesis was induced in the airway wall during the
      alloimmune response, which was reversed by cyclosporine A in a dose-dependent
      fashion. VEGF-C overexpression in tracheal allografts induced epithelial
      activation, neutrophil chemotaxis, and a shift toward a Th17 adaptive immune
      response, followed by enhanced lymphangiogenesis and the development of OAD. In
      contrast, inhibition of VEGF-C activity with VEGFR-3-Ig inhibited
      lymphangiogenesis and angiogenesis and reduced infiltration of CD4(+) T cells and
      the development of OAD. Lymphangiogenesis was linked to T-cell responses during
      the development of OAD, and VEGF-C/VEGFR-3 signaling modulated innate and
      adaptive immune responses in the development of OAD in rat tracheal allografts.
      Our results thus suggest VEGFR-3-signaling as a novel strategy to regulate T-cell
      responses in the development of obliterative bronchiolitis after lung
      transplantation.

PMID- 22959909
TI  - Paxillin regulates pulmonary arterial smooth muscle cell function in pulmonary
      hypertension.
AB  - Pulmonary hypertension (PH) is a fatal disease characterized by remodeling
      processes such as increased migration and proliferation of pulmonary arterial
      smooth muscle cells (PASMC), enhanced matrix deposition, and dysregulation of
      cytoskeletal proteins. However, the contribution of cytoskeletal proteins in PH
      is still not fully understood. In this study, we have used a yeast two-hybrid
      screen to identify novel binding partners of the cytoskeletal adaptor protein
      four-and-a-half LIM domains 1 (Fhl-1). This identified paxillin as a new Fhl-1
      interacting partner, and consequently we assessed its contribution to vascular
      remodeling processes. Native protein-protein binding was confirmed by co
      immunoprecipitation studies in murine and human PASMC. Both proteins co-localized
      in PASMC in vitro and in vivo. In lung samples from idiopathic pulmonary arterial
      hypertension patients, paxillin expression was increased on mRNA and protein
      levels. Laser-microdissection of murine intrapulmonary arteries revealed elevated
      paxillin expression in hypoxia-induced PH. Furthermore, hypoxia-dependent
      upregulation of paxillin was HIF-1alpha dependent. Silencing of paxillin
      expression led to decreased PASMC adhesion, proliferation, and increased
      apoptosis. Regulation of these processes occurred via Akt and Erk1/2 kinases. In
      addition, adhesion of PASMC to the extracellular matrix protein fibronectin was
      critically dependent on paxillin expression. To summarize, we identified paxillin
      as a new regulator protein of PASMC growth.

PMID- 22959912
TI  - On the need for competent evaluation of trial quality.

PMID- 22959908
TI  - Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular
      remodeling in an in vivo human placentation model.
AB  - We investigated human cytomegalovirus pathogenesis by comparing infection with
      the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory
      strain AD169 in human placental villi as explants in vitro and xenografts
      transplanted into kidney capsules of SCID mice (ie, mice with severe combined
      immunodeficiency). In this in vivo human placentation model, human
      cytotrophoblasts invade the renal parenchyma, remodel resident arteries, and
      induce a robust lymphangiogenic response. VR1814 replicated in villous and cell
      column cytotrophoblasts and reduced formation of anchoring villi in vitro. In
      xenografts, infected cytotrophoblasts had a severely diminished capacity to
      invade and remodel resident arteries. Infiltrating lymphatic endothelial cells
      proliferated, aggregated, and failed to form lymphatic vessels. In contrast,
      AD169 grew poorly in cytotrophoblasts in explants, and anchoring villi formed
      normally in vitro. Likewise, viral replication was impaired in xenografts, and
      cytotrophoblasts retained invasive capacity, but some partially remodeled blood
      vessels incorporated lymphatic endothelial cells and were permeable to blood. The
      expression of both vascular endothelial growth factor (VEGF)-C and basic
      fibroblast growth factor increased in VR1814-infected explants, whereas VEGF-A
      and soluble VEGF receptor-3 increased in those infected with AD169. Our results
      suggest that viral replication and paracrine factors could undermine vascular
      remodeling and cytotrophoblast-induced lymphangiogenesis, contributing to
      bleeding, hypoxia, and edema in pregnancies complicated by congenital human
      cytomegalovirus infection.

PMID- 22959913
TI  - A branching process model of ovarian cancer.
AB  - Ovarian cancer is usually diagnosed at an advanced stage, rendering the
      possibility of cure unlikely. To date, no cost-effective screening test has
      proven effective for reducing mortality. To estimate the window of opportunity
      for ovarian cancer screening, we develop a branching process model for ovarian
      cancer growth and progression accounting for three cell populations: Primary
      (cells in the ovary or fallopian tube), Peritoneal (viable cells in peritoneal
      fluid), and Metastatic (cells implanted on other intra-abdominal surfaces).
      Growth and migration parameters were chosen to match results of clinical studies.
      Using these values, our model predicts a window of opportunity of 2.9 years,
      indicating that one would have to screen at least every other year to be
      effective. The model can be used to inform future efforts in designing improved
      screening and treatment strategies.

PMID- 22959915
TI  - Investigating hemispheric lateralization of reflexive attention to gaze and arrow
      cues.
AB  - Recent studies have demonstrated that central cues, such as eyes and arrows,
      reflexively trigger attentional shifts. However, it is not clear whether the
      attentional mechanisms induced by these two cues are similar or rather differ in
      some important way. We investigated hemispheric lateralization of the orienting
      effects induced by the two cue types in a group of 48 healthy participants
      comparing arrows and eye gaze as central non-predictive cues in a discrimination
      task, in which a target stimulus was briefly presented in one of two peripheral
      positions (left or right of fixation). As predicted by neuropsychological data,
      reflexive orienting to gaze cues was only observed when the target was presented
      in the left visual field, whereas reflexive orienting to arrow cues occurred for
      targets presented in both left and right visual fields.

PMID- 22959916
TI  - Role of frontal cortex in attentional capture by singleton distractors.
AB  - The role of frontal cortex in selective attention to visual distractors was
      examined in an attentional capture task in which participants searched for a
      unique shape in the presence or absence of an additional colour singleton
      distractor. The presence of the additional singleton was associated with slower
      behavioural responses to the shape target, and a greater neural signal in
      inferior frontal gyrus. To investigate the involvement of cognitive control
      functions of the frontal lobes in the capture of attention by the additional
      singletons, we measured the effect of the additional singleton in a context of
      either low or high working memory load. Whereas behavioural capture was
      unaffected by the level of load on working memory, greater activity associated
      with the presence of the additional singleton was observed in inferior frontal
      gyrus, but only under high load. This effect was greater in participants who
      experienced greater capture. We argue that the role of inferior frontal gyrus in
      selective attention is to detect potential sources of distraction.

PMID- 22959914
TI  - Modeling Plasmodium vivax: relapses, treatment, seasonality, and G6PD deficiency.
AB  - Plasmodium vivax (P. vivax) is one of the most important human malaria species
      that is geographically widely endemic and causes social and economic burden
      globally. However, its consequences have long been neglected and underestimated
      as it has been mistakenly considered a benign and inconsequential malaria species
      as compared to Plasmodium falciparum. One of the important differences between P.
      falciparum and P. vivax is the formation of P. vivax latent-stage parasites
      (hypnozoites) that can cause relapses after a course of treatment. In this work,
      mathematical modeling is employed to investigate how patterns of incubation
      periods and relapses of P. vivax, variation in treatment, and seasonal abundance
      of mosquitoes influence the number of humans infected with P. vivax and the mean
      age at infection of humans in tropical and temperate regions. The model predicts
      that: (i) the number of humans infected with P. vivax may increase when an
      incubation period of parasites in humans and a latent period of hypnozoites
      decrease; (ii) without primaquine, the only licensed drug to prevent relapses, P.
      vivax may be highly prevalent; (iii) the mean age at infection of humans may
      increase when a latent period of hypnozoites increases; (iv) the number of
      infectious humans may peak at a few months before the middle of each dry season
      and the number of hypnozoite carriers may peak at nearly the middle of each dry
      season. In addition, glucose-6-phosphate-dehydrogenase (G6PD) deficiency, which
      is the most common enzyme defect in humans that may provide some protection
      against P. vivax infection and severity, is taken into account to study its
      impact on the number of humans infected with P. vivax. Modeling results indicate
      that the increased number of infected humans may result from a combination of a
      larger proportion of humans with G6PD deficiency in the population, a lesser
      protection of G6PD deficiency to P. vivax infection, and a shorter latent period
      of hypnozoites.

PMID- 22959917
TI  - Presence of the bla(Z) beta-lactamase gene in isolates of Staphylococcus aureus
      that appear penicillin susceptible by conventional phenotypic methods.
AB  - Beta-lactamase production may not be reliably detected by commonly used
      susceptibility testing methods such as Kirby-Bauer penicillin disk diffusion and
      nitrocefin beta-lactamase detection. We assayed 105 apparently penicillin
      susceptible Staphylococcus aureus isolates using multiple methods to detect beta
      lactamase production. The bla(Z) beta-lactamase gene was detected by polymerase
      chain reaction in 10 (9.5%) of the 105 isolates. The average disk diffusion zone
      diameter was 34 and 38 mm for the bla(Z)-positive and -negative isolates,
      respectively (P < 0.001). Qualitative description of the zone edge was observer
      dependent. The "cloverleaf assay" was positive in 6 of the 10 phenotypically
      susceptible isolates possessing bla(Z). The results of this study suggest that
      conventional methods for S. aureus penicillin susceptibility testing may not
      reliably detect penicillin resistance in all isolates; however, increasing the
      disk diffusion zone size interpretive criteria to 35 mm for this
      antimicrobial/organism combination from the current 29-mm breakpoint may improve
      the sensitivity of phenotypic penicillin susceptibility testing.

PMID- 22959918
TI  - Pacemaker-associated Bacillus cereus endocarditis.
AB  - We report the case of a pacemaker-associated Bacillus cereus endocarditis in a
      nonimmunocompromised patient. Antibiotic treatment was ineffective, and the
      pacemaker had to be removed. B. cereus was cultured from several blood samples
      and from the pacemaker electrodes. This case underlines the contribution of the
      rpoB gene for Bacillus species determination.

PMID- 22959919
TI  - Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection
      and treatment of synovial inflammation in murine rheumatoid arthritis.
AB  - We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS)
      to selectively image and eradicate inflammatory lesions in rheumatoid arthritis
      (RA). Thrombin is a serine protease up-regulated in synovial tissues of
      rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to
      which multiple photosensitizer (PS) units are tethered via short thrombin
      cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug
      are efficiently quenched due to the interaction of neighboring photosensitizer
      units. The prodrug is passively delivered to the inflammation site via the
      enhanced permeability and retention (EPR) effect. Subsequent site-selective
      proteolytic cleavage of the peptide linkers restores its photoactivity by
      increasing the mutual distance between PS. Whole animal imaging in murine
      collagen-induced arthritis, an experimental model of RA revealed a dose-dependent
      fluorescence increase in arthritic paws after systemic prodrug injection. In
      addition, administration of T-PS resulted in much higher fluorescence selectivity
      for arthritic joints as compared to the free PS. Irradiation of the arthritic
      joints induced light dose dependent phototoxic effects such as apoptosis,
      vascular damage and local hemorrhage. Long-term observations showed complete
      regression of the latter. Irradiated non-arthritic tissues or non-irradiated
      arthritic tissues showed no histological effects after photodynamic therapy with
      T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent
      selectivity and induce apoptosis and vascular shut down after irradiation.

PMID- 22959920
TI  - Delayed postconditioning: not too late?
AB  - Ischemic postconditioning applied at the onset of reperfusion reduces myocardial
      infarction in both animals and humans. Our recent study on the mouse myocardium
      showed for the first time that delayed postconditioning (applied up to 30 min
      after the onset of reperfusion) can decrease infarct size. The existence of a
      longer cardioprotection window is conceptually relevant for clinical application
      and also in the case of a pharmacological strategy.

PMID- 22959921
TI  - Video-assisted thoracoscopic lobectomy is associated with better perioperative
      outcomes than open lobectomy in a veteran population.
AB  - BACKGROUND: We sought to establish the feasibility and efficacy of video-assisted
      thoracoscopic (VATS) lobectomy in treating lung cancer in a veteran population.
      METHODS: We retrospectively analyzed preoperative, intraoperative, and
      postoperative parameters in 46 VATS versus 45 open lobectomy patients at a single
      center. RESULTS: The 2 groups were similar in preoperative and intraoperative
      variables. Although surgical mortality was not significantly different after
      lobectomy performed with VATS (0 of 46) compared with open lobectomy (2 of 45,
      4%; P = .2), there were fewer complications in VATS patients (14 of 46, 30%) than
      their open counterparts (26 of 45, 58%; P = .009). VATS patients also had a
      shorter chest tube duration and length of stay. In multivariate analysis, VATS
      was associated independently with a reduced risk of complications (odds ratio,
      .359; P = .04). CONCLUSIONS: VATS lobectomy in a veteran population is feasible
      and safe and may lead to better perioperative outcomes than open thoracotomy
      without compromising oncologic principles.

PMID- 22959922
TI  - Discrimination of influenza virus-infected nasal fluids by Vis-NIR spectroscopy.
AB  - BACKGROUND: Influenza patients show a severe condition of the respiratory tract
      with high temperature. Efficient treatment of influenza requires early use of
      oseltamivir, and thus rapid diagnosis is needed. Recently, rapid diagnostic
      methods such as immunochromatography have been developed; however,
      immunochromatography is not an optimal technique because it is relatively
      expensive and has low sensitivity. METHODS: Visible and near-infrared (Vis-NIR)
      spectroscopy in the region 600-1100 nm, combined with chemometrics analysis such
      as principal component analysis (PCA) or soft modeling of class analogy (SIMCA),
      was used to develop a potential diagnostic method for influenza based on nasal
      aspirates from infected patients. RESULTS: The Vis-NIR spectra of nasal aspirates
      from 33 non-influenza patients and 34 influenza patients were subjected to PCA
      and SIMCA to develop multivariate models to discriminate between influenza and
      non-influenza patients. These models were further assessed by the prediction of
      126 masked measurements [30 from non-influenza patients, 30 from influenza
      patients and 66 from patients infected with respiratory syncytial virus (RSV)].
      The PCA model showed some discrimination of the masked samples. The SIMCA model
      correctly predicted 29 of 30 (96.7%) non-influenza patients, and 30 of 30 (100%)
      influenza patients from the Vis-NIR spectra of masked nasal aspirate samples.
      Nasal aspirates of RSV-infected patients were predicted as 50% non-influenza and
      50% influenza by the SIMCA model, suggesting that discrimination between patients
      infected with influenza virus and those infected with RSV was difficult.
      CONCLUSIONS: Although the study sample was small and there was difficulty in
      discriminating between influenza virus and RSV infection, these results suggest
      that Vis-NIR spectroscopy of nasal aspirates, combined with chemometrics
      analysis, might be a potential tool for diagnosis of influenza.

PMID- 22959923
TI  - TaqMan real-time polymerase chain reaction for detection of SEC1-FUT2 hybrid
      alleles: identification of novel hybrid allele.
AB  - BACKGROUND: Two hybrid alleles between the secretor type
      alpha(1,2)fucosyltransferase gene (FUT2) and a pseudogene of FUT2 (SEC1) have
      been reported so far; parts of the SEC1 and FUT2 sequences are suggested to be
      susceptible to recombination. The se(fus), one of the two hybrid alleles, is
      found in Japanese populations at relative high frequencies. METHODS: A TaqMan
      assay to distinguish SEC1 and SEC1-FUT2 hybrid alleles was designed for the
      purpose of dealing with large number of samples. RESULTS: The results of the
      present method were fully consistent with those of the previous method for
      detection of se(fus) in the Japanese population. In addition, a novel SEC1-FUT2
      SEC1 hybrid allele, which contains a 35-bp sequence (between positions 418 and
      452) that is identical to the FUT2 sequence including a 13-bp FUT2-specific
      region (between positions 436 and 448), was encountered in an individual of
      European descent. CONCLUSIONS: The present TaqMan assay is a reliable and
      powerful method for the large scale association study between disease
      susceptibility and FUT2 genotypes especially in the Japanese populations because
      of relative high frequency of se(fus). In addition, this method is a useful tool
      to find novel SEC1-FUT2 hybrid alleles.

PMID- 22959924
TI  - Serum levels of N-terminal fragment of precursor protein brain-type natriuretic
      peptide (NT-proBNP) in twin pregnancy.
AB  - Twin pregnancy differs considerably from singleton pregnancy in many aspects and
      it is unknown how serum NT-proBNP level behaves in women with twin pregnancies.
      Serum NT-proBNP levels were determined longitudinally at gestational weeks (GW)
      24 and 35 in normotensive women with 13 twin and 99 singleton pregnancies. The
      effects of maternal demographic characteristics on NT-proBNP levels were also
      analyzed. The serum NT-proBNP levels (pg/ml) in twin pregnancies, which were not
      different from those in singleton pregnancies at 24 GW (26+/-15 vs. 40+/-27,
      respectively, P=0.0718), increased significantly (P=0.0038) and were
      significantly higher than those in singleton pregnancies at 35 GW (72+/-49 vs.
      34+/-24, P<0.0001). In the analysis including women with singleton pregnancies,
      the serum levels of NT-proBNP at 35 GW were significantly inversely correlated
      with pre-pregnancy body mass index (BMI, kg/m(2)) and were significantly higher
      in nulliparous than multiparous women. Thus, women with twin pregnancy were
      likely to exhibit an increase in serum NT-proBNP levels in the late stage of
      pregnancy, especially in lean and nulliparous women. The relative greater blood
      volume expansion occurring in twin than in singleton pregnancies was considered
      to be responsible for this phenomenon.

PMID- 22959925
TI  - Involvement of the Nrf2-proteasome pathway in the endoplasmic reticulum stress
      response in pancreatic beta-cells.
AB  - The ubiquitin-proteasome system plays a central role in protein quality control
      through endoplasmic reticulum (ER)-associated degradation (ERAD) of unfolded and
      misfolded proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that
      controls the expression of an array of phase II detoxification and antioxidant
      genes. Nrf2 signaling has additionally been shown to upregulate the expression of
      the proteasome catalytic subunits in several cell types. Here, we investigated
      the role of Nrf2 in tunicamycin-induced ER stress using a murine insulinoma beta
      cell line, betaTC-6. shRNA-mediated silencing of Nrf2 expression in betaTC-6
      cells significantly increased tunicamycin-induced cytotoxicity, elevated the
      expression of the pro-apoptotic ER stress marker Chop10, and inhibited
      tunicamycin-inducible expression of the proteasomal catalytic subunits Psmb5 and
      Psmb6. The effects of 3H-1,2-dithiole-3-thione (D3T), a small molecule Nrf2
      activator, on ER stress were also examined in betaTC-6 cells. D3T pretreatment
      reduced tunicamycin cytotoxicity and attenuated the tunicamycin-inducible Chop10
      and protein kinase RNA-activated-like ER kinase (Perk). The protective effect of
      D3T was shown to be associated with increased ERAD. D3T increased the expression
      of Psmb5 and Psmb6 and elevated chymotrypsin-like peptidase activity; proteasome
      inhibitor treatment blocked D3T effects on tunicamycin cytotoxicity and ER stress
      marker changes. Similarly, silencing of Nrf2 abolished the protective effect of
      D3T against ER stress. These results indicate that the Nrf2 pathway contributes
      to the ER stress response in pancreatic beta-cells by enhancing proteasome
      mediated ERAD.

PMID- 22959926
TI  - Autophagy induction by silver nanowires: a new aspect in the biocompatibility
      assessment of nanocomposite thin films.
AB  - Nanomaterials and their enabled products have increasingly been attracting global
      attention due to their unique physicochemical properties. Among these emerging
      products, silver nanowire (AgNW)-based thin films are being developed for their
      promising applications in next generation nanoelectronics and nanodevices.
      However, serious concerns remain about possible health and safety risks they may
      pose. Here, we employed a multi-modal systematic biocompatibility assessment of
      thin films incorporating AgNW. To represent the possible routes of nanomaterial
      entry during occupational or environmental exposure, we employed four different
      cell lines of epithelial, endothelial, gastric, and phagocytic origin. Utilizing
      a cell-based automated image acquisition and analysis procedure in combination
      with real-time impedance sensing, we observed a low level of cytotoxicity of
      AgNW, which was dependent on cell type, nanowire lengths, doses and incubation
      times. Similarly, no major cytotoxic effects were induced by AgNW-containing thin
      films, as detected by conventional cell viability and imaging assays. However,
      transmission electron microscopy and Western immunoblotting analysis revealed
      AgNW-induced autophasosome accumulation together with an upregulation of the
      autophagy marker protein LC3. Autophagy represents a crucial mechanism in
      maintaining cellular homeostasis, and our data for the first time demonstrate
      triggering of such mechanism by AgNW in human phagocytic cells. Finally, atomic
      force microscopy revealed significant changes in the topology of cells attaching
      and growing on these films as substrates. Our findings thus emphasize the
      necessity of comprehensive biohazard assessment of nanomaterials in modern
      applications and devices and a thorough analysis of risks associated with their
      possible contact with humans through occupational or environmental exposure.

PMID- 22959927
TI  - Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by
      stabilizing mast cells through modulating Ca2+ mobilization.
AB  - Mast cells play a key role in the pathogenesis of asthma and are a promising
      target for therapeutic intervention in asthma. This study investigated the
      effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation
      upon cross-linking of the high-affinity IgE receptors (FcepsilonRI), as well as
      the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD
      treatment for 30 min suppressed FcepsilonRI-mediated mast cell degranulation in a
      dose-dependent manner. Concomitantly, PD significantly decreased FcepsilonRI
      mediated Ca2+ increase in mast cells. The suppressive effects of PD on
      FcepsilonRI-mediated Ca2+ increase were largely inhibited by using LaCl3 to block
      the Ca2+ release-activated Ca2+ channels (CRACs). Furthermore, PD significantly
      inhibited Ca2+ entry through CRACs evoked by thapsigargin (TG). Knocking down
      protein expression of Orai1, the pore-forming subunit of CRACs, significantly
      decreased PD suppression of FcepsilonRI-induced intracellular Ca2+ influx and
      mast cell degranulation. In a mouse model of mast cell-dependent passive
      cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell
      degranulation and inhibited anaphylaxis. Taken together, our data indicate that
      PD stabilizes mast cells by suppressing FcepsilonRI-induced Ca2+ mobilization
      mainly through inhibiting Ca2+ entry via CRACs, thus exerting a protective effect
      against PCA.

PMID- 22959929
TI  - Immunoreactivity of Ki-67/beta-tubulin and immunocolocalization with active
      caspase-3 in rat dentate gyrus during postnatal development.
AB  - This study was based on our previous report that the expression of active caspase
      3 kept at a high level in dentate gyrus during postnatal development, which is
      not related to an apoptotic event. We addressed the hypothesis that the active
      caspase-3 expression may be related to a nonapoptotic role in the regulation of
      the cell cycle and differentiation or other physiological functions. To confirm
      this hypothesis, through a temporal investigation from postnatal day (P) 0, 4, 7,
      10, 14, 21, 28, to 56, based on immunofluorescent method, we dual labeled active
      caspase-3 with Ki-67 or beta-tubulin in the dentate gyrus. Our results showed a
      minority of active caspase-3 positive cells were colabeled with the proliferation
      marker Ki-67 in stratum moleculare (MOL), granular cell layer (GCL), subgranular
      zone (SGZ) and polymorphic stratum (POLY) from P0 to P14, and the colabeled cells
      decreased gradually with age. From P21 to P56, the colocalization of the two
      proteins was mainly focused on SGZ. There was a positive correlation between the
      positive cells of active caspase-3 with that of Ki-67. In addition, an extensive
      colocalization between active caspase-3 and beta-tubulin was observed at all the
      age groups. There was a strong positive correlation between the intensity of
      active caspase-3 in GCL with that of beta-tubulin in MOL, GCL and POLY of dentate
      gyrus and the stratum lucidum of CA3. Our data raised the possibility of a
      nonapoptotic role of active caspase-3 in dentate gyrus, which may be partly
      associated with cellular proliferation and differentiation, and also may be
      related to neurite outgrowth, axonal transport, or dendrite elongation of
      granular cells during postnatal development.

PMID- 22959930
TI  - Thyroid stimulating hormone, free thyroxine and cognitive ability in old age: the
      Lothian Birth Cohort Study 1936.
AB  - The current study investigated the associations between thyroid stimulating
      hormone (TSH), free thyroxine (T(4)) and cognitive ability (general ability,
      memory and processing speed), in a large age homogenous sample (n=659) of
      generally healthy euthyroid older adults. Associations were considered both at
      baseline (mean age wave 1=69.5 years; SD=0.8 years) and approximately 3 years
      later (mean age wave 2=72.5 years; SD=0.7 years). Results indicated mean level
      decreases across waves in both TSH (t=10.99, p<0.001) and T(4) (t=34.55,
      p<0.001). There were no significant associations between TSH and T(4) with any of
      the cognitive variables at either wave. There was no suggestion of non-linear
      associations. The lack of associations supports suggestions that the effects of
      thyroid hormones on cognition may be restricted to older individuals above a
      given threshold, and/or those with levels of thyroid hormones within the range
      defining clinical thyroid disorder.

PMID- 22959928
TI  - The epigenetic effects of a high prenatal folate intake in male mouse fetuses
      exposed in utero to arsenic.
AB  - Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous
      studies have demonstrated that in utero exposure to iAs promotes cancer in adult
      mouse offspring, possibly acting through epigenetic mechanisms. Humans and
      rodents enzymatically convert iAs to its methylated metabolites. This reaction
      requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required
      for DNA methylation. Supplementation with folate, a major dietary source of
      methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the
      adverse effects of iAs exposure. However, effects of gestational folate
      supplementation on iAs metabolism and fetal DNA methylation have never been
      thoroughly examined. In the present study, pregnant CD1 mice were fed control
      (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from
      gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite)
      from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18
      fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in
      fetal livers. High folate intake lowered the burden of total arsenic in maternal
      livers but did not prevent the effects of iAs exposure on fetal weight or hepatic
      SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further
      significant body weight reduction. Notably, iAs exposure alone had little effect
      on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure
      changed the CpG island methylation in 2,931 genes, including genes known to be
      imprinted. Most of these genes were associated with neurodevelopment, cancer,
      cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which
      regulates fetal development, was among the most affected biological pathways.
      Taken together, our results suggest that a combined in utero exposure to iAs and
      a high folate intake may adversely influence DNA methylation profiles and weight
      of fetuses, compromising fetal development and possibly increasing the risk for
      early-onset of disease in offspring.

PMID- 22959931
TI  - The effects of viral vaccination of dairy heifer calves on the incidence of
      respiratory disease, mortality, and growth.
AB  - Bovine respiratory disease (BRD) is one of the most common infectious causes of
      morbidity and mortality in young dairy cattle. The objective of this randomized
      clinical trial was to determine the effectiveness of 1 or 2 doses of a 5-way,
      modified-live viral vaccine, administered to heifer calves before weaning to aid
      in the prevention of BRD. The hypotheses were that vaccination would reduce the
      incidence of BRD and mortality, and that 2 doses would be more effective than 1.
      A total of 2,874 heifer calves from 19 commercial dairy farms in Minnesota and
      Ontario were enrolled at 1 to 7d of age and were followed until 3 mo of age.
      Calves were randomly assigned to receive a commercial, intramuscular, modified
      live vaccine against bovine viral diarrhea virus types 1 and 2, bovine
      respiratory syncytial virus, bovine herpesvirus type 1, and parainfluenza virus
      type 3 at 15 to 21 d of age (2 wk only), 35 to 42 d (5 wk only), both 2 and 5 wk,
      or sterile saline at both times (unvaccinated controls). The incidence of failure
      of passive transfer was 11 or 32%, using cut-points of serum total protein of 5.2
      and 5.7 g/dL, respectively. Overall, 22% of calves were treated at least once for
      BRD. The incidence risk of naturally occurring BRD was 7.7% before 2 wk of age,
      8.0% between 2 and 5 wk, and 9.5% between 5 wk and 3 mo of age, and was not
      different between vaccination groups. Overall mortality throughout the 3-mo study
      period was 3.5%. Mortality was 1.6% before 2 wk of age, 0.5% between 2 and 5 wk,
      and 1.2% between 5 wk and 3 mo of age. The risk of mortality was not affected by
      vaccination. Mean average daily gain of 1.07 kg/d from 5 wk to 3 mo of age was
      not different between vaccine groups. In this population of commercial, home
      raised calves, with an overall low incidence of failure of passive transfer,
      intramuscular vaccination with a multivalent, modified live viral vaccine at 2 or
      5 wk of age or both was not associated with a decreased risk of BRD or mortality,
      or with growth until 3 mo of age. Reasons for these findings may include
      interference by maternal antibodies, unresponsiveness of the neonatal immune
      system, timing of immunity relative to pathogen exposure, disease caused by
      pathogens other than the viruses in the vaccine, or herd immunity. However, in
      populations with higher incidence of failure of passive transfer or risk of BRD,
      calves with low levels of specific antibodies may respond differently to
      vaccination.

PMID- 22959932
TI  - Validation of an automated method to count steps while cows stand on a weighing
      platform and its application as a measure to detect lameness.
AB  - Weight shifting between legs and steps taken when cows stand may be a useful tool
      to assess cow comfort and lameness. Weight shifting is assessed by measuring the
      distribution of weight applied to each leg when standing on a weighing platform,
      whereas frequency of steps is traditionally measured with live observation or
      video recording. The objectives of this study were to validate an automated
      method to count steps from weight distribution measurements (experiment 1) and to
      assess the accuracy of the frequency of steps in detecting lameness (experiment
      2). In experiment 1, 6 nonlame multiparous cows stood on a weighing platform
      covered with either concrete or rubber (1h/cow per surface) while stepping
      behavior was video recorded. Receiver operating characteristic curves were
      constructed, using the steps observed in the video recordings as the gold
      standard, to calculate the optimal threshold (based on the sum of sensitivity and
      specificity) of the weight applied to a leg to define a step. Optimal thresholds
      were similar between surfaces. The optimal thresholds, when pooling the 2
      surfaces, were 127 and 98 kg for the front and rear pair for legs, respectively,
      with a specificity and sensitivity >=0.96. Thresholds were used to construct an
      algorithm to count steps. In experiment 2, 57 cows (26 of them considered lame
      according to their gait score) stood for 15 min on the weighing platform.
      Frequency of steps taken with the front and rear pair of legs was calculated from
      the weight distribution measurements using the algorithm calculated in experiment
      1. Lame cows took more steps per minute with the rear legs than did nonlame cows
      (1.6 vs. 1.0 steps/min; SE of the difference=0.2). As previously shown for weight
      shifting, the frequency of steps taken with the rear legs was a good predictor of
      lameness (area under the curve of the receiver operating characteristic
      curve=0.67; 95% confidence interval=0.52, 0.81). A positive relationship was
      observed between the frequency of steps and weight shifting (measured as SD of
      the weight applied over time to the legs) in both the front (R(2)=0.35) and rear
      (R(2)=0.49) legs, yet the slopes differed from 1 and the intercepts differed from
      0, indicating that the 2 measures were related but not the same. In conclusion,
      weighing platforms can accurately calculate the frequency of steps automatically,
      and this measure shows promise as a tool to assess lameness.

PMID- 22959933
TI  - Short communication: in vivo deposition of [1-13C]vaccenic acid and the product
      of its Delta9-desaturation, [1-13C]rumenic acid, in the body tissues of lactating
      goats fed oils.
AB  - This study was conducted in lactating goats with the aim of measuring the
      deposition of trans-11 18:1 (vaccenic acid, VA) and the product of its Delta(9)
      desaturation, cis-9, trans-11 18:2 (rumenic acid, RA), in the major tissues that
      are involved in lipid metabolism in the lactating ruminant (i.e., mammary
      secretory tissue, liver, and omental and perirenal adipose tissues) and examining
      its potential link with variations in the expression of genes encoding Delta(9)
      desaturase [stearoyl-CoA desaturases 1 and 5 (SCD1 and SCD5)]. Eight lactating
      goats were fed a diet supplemented with sunflower oil (n=4) or sunflower oil plus
      fish oil and additional starch (n=4), based on the hypothesis that these dietary
      treatments could affect Delta(9)-desaturase gene expression in specific tissues.
      A chemical tracer, 1.5 g of [1-13C]VA as nonesterified fatty acid, was delivered
      by jugular injection. Goats were slaughtered 4 d later, and tissue samples were
      collected for the measurement of [13C]VA and [13C]RA enrichment and SCD1 and SCD5
      expression. The addition of fish oil and additional starch to a diet containing
      sunflower oil was associated with several changes in [13C]VA and [13C]RA
      enrichment. These results support previous studies suggesting that mammary
      secretory tissue is the primary site of Delta(9)-desaturation in lactating goats.
      In adipose tissues, the [13C]VA + [13C]RA enrichment was consistent with a net
      uptake of circulating fatty acids to reconstitute body reserves at the end of the
      lactation cycle. The putative uptake of [13C]RA synthesized by other tissues
      precludes any conclusion from being drawn regarding potential Delta(9)
      desaturation in the liver of goats, despite the detection of SCD1 and SCD5 mRNA
      in this tissue. Finally, no significant effect of dietary treatment was observed
      for SCD1 or SCD5 mRNA abundance in the mammary secretory tissue or other body
      tissues.

PMID- 22959934
TI  - Corium tissue expression of genes associated with inflammation, oxidative stress,
      and keratin formation in relation to lameness in dairy cows.
AB  - Objectives were to (1) determine the feasibility of performing hoof biopsies
      without impairing locomotion; (2) evaluate the feasibility of using biopsied
      tissue for quantitative PCR; and (3) compare relative gene expression among claws
      for several target genes. Biopsies were performed on 6 Holstein cows, yielding 4
      tissue specimens per cow from front leg, right limb, and medial claw (claw
      position 3); rear leg, left limb, and lateral claw (claw position 5); and rear
      leg, right limb, medial claw (claw position 7). Cows were monitored for lameness
      daily for 7 d post-biopsy and then weekly for 8 wk. Histopathological analysis
      confirmed that tissue collected was from between the stratum corneum and dermis.
      Biopsied tissue was used for RNA extraction, including evaluation of yield and
      purity. The profile by claw position of 19 genes with key functions in cell
      differentiation, proliferation, inflammation, and keratin formation was assessed
      via quantitative reverse transcription-PCR. Other than transient disturbances in
      locomotion score in some cows during 2 to 4 d post-biopsy, no signs of pain,
      locomotion impairment, or clinical lameness were observed post-biopsy. Total RNA
      yields averaged 259.7+/-100, 447.8+/-288, and 496.4+/-118 MUg/mg of tissue for
      claw positions 3, 5, and 7, respectively. The biopsy procedure was successful for
      obtaining corium for gene expression. Among 5 keratin proteins analyzed, only
      keratin 5 was expressed. Transcripts related to inflammation and oxidative stress
      (STAT3, MYD88, SOD2, and TLR4) were among the more abundant in corium tissue, but
      expression did not differ between claws. Biotinidase (BTD) expression was greater
      in claw 3 versus claw 5, whereas the ligand-activated nuclear receptor retinoic
      acid receptor-alpha (RXRA) was greater in claws 3 + 5 compared with claw 7.
      Overall, results from this pilot study revealed modest differences at the
      transcriptome level, suggesting that biotin availability and lipid metabolism
      differ between claw positions, whereas inflammation and oxidative stress seem to
      play an important role across claws. More comprehensive studies of the hoof
      transcriptome are required to improve our understanding of the mechanisms that
      link environmental and dietary factors to development of lameness.

PMID- 22959935
TI  - Behavior of Enterobacter pulveris in amorphous and crystalline powder matrices
      treated with supercritical carbon dioxide.
AB  - The resistance of an Enterobacter pulveris strain to combined heat and
      supercritical carbon dioxide (scCO(2)) treatments in different powder matrices
      was examined. The strain proved resistant to scCO(2) treatment up to 50 MPa
      pressure at temperatures >73  degrees C for at least 20 min in a commercial
      infant formula. Water availability was shown to be important for the observed
      thermotolerance, because introduction of water in the scCO(2) gas flow during
      treatment resulted in a 1 log(10) cfu/g reduction of the initial inoculum.
      Interestingly, similar tolerance to heat and scCO(2) treatment was observed in a
      less complex matrix, a maltodextrin powder. In contrast, the bacterial strain
      proved sensitive to lower temperatures (55-65  degrees C) over shorter times
      (<=10 min) in a dextrose powder composed of crystalline particles. Therefore, the
      microorganism demonstrates heat sensitivity in the crystalline powder matrix
      closer to that of nonpowder liquid matrices. These data demonstrate the increased
      heat tolerance of the bacterium specifically in amorphous powders and indicate
      that this characteristic is not dependent on fat and other components commonly
      found in infant formula. The information is important in designing strategies to
      deal with contamination of powders with Enterobacteriacae, including pathogenic
      Cronobacter spp.

PMID- 22959936
TI  - Bioinformatics analysis of microRNA and putative target genes in bovine mammary
      tissue infected with Streptococcus uberis.
AB  - MicroRNA (miRNA) are small single-stranded noncoding RNA with important roles in
      regulating innate immunity in nonruminants via transcriptional and
      posttranscriptional mechanisms. Mastitis causes significant losses in the dairy
      industry and a wealth of large-scale mRNA expression data from mammary tissue
      have provided fundamental insights into the tissue adaptations to pathogens. We
      studied the expression of 14 miRNA (miR-10a, -15b, -16a, -17, -21, -31, -145, 
      146a, -146b, -155, -181a, -205, -221, and -223) associated with regulation of
      innate immunity and mammary epithelial cell function in tissue challenged with
      Streptococcus uberis. Those data, along with microarray expression of 2,102
      differentially expressed genes, were used for bioinformatics analysis to uncover
      putative target genes and the most affected biological pathways and functions.
      Three miRNA (181a, 16, and 31) were downregulated approximately 3- to 5-fold and
      miR-223 was upregulated approximately 2.5-fold in infected versus healthy tissue.
      Among differentially expressed genes due to infection, bioinformatics analysis
      revealed that the studied miRNA share in the regulation of a large number of
      metabolic (SCD, CD36, GPAM, and FASN), immune/oxidative stress (TNF, IL6, IL10,
      SOD2, LYZ, and TLR4), and cellular proliferation/differentiation (FOS and CASP4)
      target genes. This level of complex regulation was underscored by the coordinate
      effect revealed by bioinformatics on various cellular pathways within the Kyoto
      Encyclopedia of Genes and Genomes database. Most pathways associated with
      "cellular processes," "organismal systems," and "diseases" were activated by
      putative target genes of miR-31 and miR-16a, with an overlapping activation of
      "immune system" and "signal transduction." A pronounced effect and activation of
      miR-31 target genes was observed within "folding, sorting, and degradation,"
      "cell growth and death," and "cell communication" pathways, whereas a marked
      inhibition of "lipid metabolism" occurred. Putative targets of miR-181a had a
      strong effect on FcgammaR-mediated phagocytosis, toll-like receptor signaling,
      and antigen processing and presentation, which were activated during intramammary
      infections. The targets of both miR-31 and miR-223 had an inhibitory effect on
      "lipid metabolism." Overall, the combined analyses indicated that changes in
      mammary tissue immune, metabolic, and cell growth-related signaling pathways
      during infection might have been mediated in part through effects of miRNA on
      gene transcription. Differential expression of miRNA supports the view from
      nonruminant cells/tissues that certain miRNA might be essential for the tissue's
      adaptive response to infection.

PMID- 22959937
TI  - A metabolomics approach to uncover the effects of grain diets on rumen health in
      dairy cows.
AB  - Dairy cows fed high-grain diets during early lactation have a high incidence of
      metabolic disorders. However, the precise mechanism(s) of how grain feeding
      causes disease is not clear. In an effort to understand how this diet transition
      alters the rumen environment and potentially leads to certain metabolic disorders
      in dairy cattle, we undertook a comprehensive, quantitative metabolomic analysis
      of rumen fluid samples from dairy cows fed 4 different diets. Using a combination
      of proton nuclear magnetic resonance spectroscopy, gas chromatography-mass
      spectrometry, and direct flow injection tandem mass spectroscopy, we identified
      and quantified 93 metabolites in rumen samples taken from 8 dairy cows fed graded
      amounts of barley grain (i.e., 0, 15, 30, and 45% of diet dry matter). We also
      studied temporal changes in the rumen by studying metabolite concentration
      differences between the first day and the last day of each diet phase following
      the diet adaptation period. Multivariate analysis showed that rumen metabolites
      arising from the diet containing 45% barley grain were clearly different from
      those containing 0, 15, and 30% barley grain. Likewise, a clear separation of the
      metabolic composition of the ruminal fluid was evident at the beginning and at
      the end of each diet phase-contrary to the belief that 11 d are suitable for the
      adaptation of cows to high-grain diets. High-grain diets (>30%) resulted in
      increased rumen fluid concentrations of several toxic, inflammatory, and
      unnatural compounds including putrescine, methylamines, ethanolamine, and short
      chain fatty acids. Perturbations in several amino acids (phenylalanine,
      ornithine, lysine, leucine, arginine, valine, and phenylacetylglycine) were also
      evident. The present study confirms and greatly extends earlier observations on
      dietary effects on rumen fluid composition and shows that the use of multiple
      metabolomic platforms permits a far more detailed understanding of metabolic
      causes and effects. These results may improve our understanding of diet-related
      rumen metabolism and the influence of grain on the overall health of dairy
      cattle.

PMID- 22959938
TI  - The effects of supplementing grazing dairy cows with partial mixed ration on
      enteric methane emissions and milk production during mid to late lactation.
AB  - This study compared the enteric CH(4) emissions and milk production of cows
      offered various grass-based diets during mid to late lactation. Forty-eight
      spring-calving Holstein-Friesian dairy cows were randomly assigned to 1 of 3
      nutritional treatments for 8 wk: (1) low grass allowance (LGA) + partial mixed
      ration (PMR), (2) high grass allowance (HGA), or (3) LGA. The PMR group received
      an allocation of 13.9 kg of grass dry matter (DM)/cow per day and in addition
      were offered 4.1 kg of PMR DM/cow per day. The HGA group received an allocation
      of 19.3 kg of grass DM/cow per day and the LGA group received an allocation of
      14.4 kg of grass DM/cow per day. The PMR offered was composed of 450 g of maize
      silage/kg of DM, 450 g of concentrate blend/kg of DM, and 100g of barley straw/kg
      of DM. Daily CH(4) emissions were determined using the emissions from ruminants
      using a calibrated tracer technique, using sulfur hexafluoride, for 5 consecutive
      days during 2 periods. Simultaneously, grass DM intake (DMI) was estimated using
      the n-alkane technique and the PMR DMI was also recorded. Cows offered PMR had
      higher DMI than either the HGA or LGA cows (16.5 vs. 14.9 and 13.9 kg of DM/d).
      The higher DMI of PMR cows increased milk production relative to HGA and LGA
      cows: milk yield (17.0 vs. 14.6 and 13.1 kg) and fat and protein yield (1.29 vs.
      1.14 and 1.04 kg). Daily CH(4) emissions were higher for the PMR group than for
      the HGA and LGA groups (406 vs. 384 and 349 g/cow per day). The enteric CH(4)
      emissions intensity per unit of DMI, milk yield, solids-corrected milk yield, and
      fat and protein yield did not differ between treatments. Effects observed in the
      PMR treatment were due to an increase in DMI rather than to any nutritional
      characteristic of the PMR.

PMID- 22959939
TI  - Brown midrib corn silage fed during the peripartal period increased intake and
      resulted in a persistent increase in milk solids yield of Holstein cows.
AB  - The objective of this study was to evaluate transition cow performance when brown
      midrib corn silage (BMRCS; Mycogen F2F444) was included in the diet during the
      transition period, and to determine if any production response occurring during
      the first 3 wk of lactation would persist from wk 4 to 15 when a common diet was
      fed. Seventy Holstein dairy cows were blocked by parity (either second or third
      and greater) and calving date and randomly assigned to the CCS (a mixture of
      varieties of conventional corn silage) or BMRCS treatment. Diets were formulated
      with the objective of keeping all ration parameters the same, with the exception
      of neutral detergent fiber digestibility. Neutral detergent fiber digestibility
      values (30 h) for CCS and BMRCS averaged 56.8 and 73.8%, respectively. Prepartum
      rations contained 47% corn silage, 18% wheat straw, 7% alfalfa haylage, and 28%
      concentrate, and averaged 45% neutral detergent fiber (DM basis). Postpartum
      rations contained 40% corn silage, 15% alfalfa haylage, 1% straw, and 44%
      concentrate. Milk weights (3*/d) and dry matter intake were recorded daily, and
      milk composition was measured weekly. Cows fed BMRCS had higher dry matter intake
      during the 2-wk period before calving (14.3 vs. 13.2 kg/d) and the 3-wk period
      after calving (20.1 vs. 18.1 kg/d) than did cows fed CCS. Yields of milk, solids,
      and lactose were increased, whereas a trend was observed for a reduction in
      somatic cell counts and linear scores in the postpartum period for cows receiving
      BMRCS during the transition. A significant carryover effect of BMRCS was observed
      on production from wk 4 to 15 when the common diet was fed, with yields of
      protein (1.36 vs. 1.30 kg/d), lactose (2.24 vs. 2.12 kg/d), and solids (5.82 vs.
      5.51 kg/d) increasing significantly, and yields of fat-corrected milk, energy
      corrected milk, and fat tending to increase during this period for cows that had
      been fed BMRCS. The increased intakes during the last 2 wk of the prepartum
      period in the BMRCS treatment were likely because of a reduction in fill, whereas
      the increased intakes in the postpartum period in cows fed the BMRCS were either
      because of the higher intakes during the prepartum period or because of a
      reduction in fill limitations in the postpartum period. The carryover response in
      wk 4 to 15 may have resulted from cows that received BMRCS during the transition
      period being in a more positive nutrient balance than cows fed CCS. The results
      of this study indicate the importance that digestible NDF can have in transition
      diets and the long-term production responses that can occur when intake is
      increased in the transition period.

PMID- 22959940
TI  - Low-protein solid feed improves the utilization of milk replacer for protein gain
      in veal calves.
AB  - This study was designed to quantify the contribution of low-protein solid feed
      (SF) intake, in addition to milk replacer, to protein and energy retention in
      veal calves. Because of potential interactions between milk replacer and SF,
      occurring at either the level of digestion or postabsorption, this contribution
      might differ from that in calves fed either SF or milk replacer alone. Forty
      eight Holstein Friesian male calves, 55+/-0.3 kg of body weight (BW), were
      divided across 16 groups of 3 calves each. Groups were assigned randomly to 1 of
      4 incremental levels of SF intake: 0, 9, 18, or 27 g of DM of SF/kg of BW(0.75)
      per day. The SF mixture consisted of 25% chopped wheat straw, 25% chopped corn
      silage, and 50% nonpelleted concentrate (on a DM basis). Each group was housed in
      a respiration chamber for quantification of energy and N balance at each of 2 BW:
      at 108+/-1.1 kg and at 164+/-1.6 kg. The milk replacer supply was 37.3g of DM/kg
      of BW(0.75) per day at 108 kg of BW and 40.7 g of DM/kg of BW(0.75) per day at
      164 kg of BW, irrespective of SF intake. Within a chamber, each calf was housed
      in a metabolic cage to allow separate collection of feces and urine. Indirect
      calorimetry and N balance data were analyzed by using regression procedures with
      SF intake-related variables. Nitrogen excretion shifted from urine to feces with
      increasing SF intake. This indicates a higher gut entry rate of urea and may
      explain the improved N utilization through urea recycling, particularly at 164 kg
      of BW. At 108 kg of BW, the gross efficiency of N retention was 61% for calves
      without SF, and it increased with SF intake by 5.4%/g of DM of SF per day. At 164
      kg of BW, this efficiency was 49% for calves without SF, and it increased by
      9.9%/g of DM of SF per day. The incremental efficiency of energy retention,
      representing the increase in energy retained per kilojoule of extra digestible
      energy intake from SF, was 41% at 108 kg of BW and 54% at 164 kg of BW.
      Accordingly, the apparent total-tract digestibility of NDF increased with BW,
      from 46% at 108 kg of BW to 56% at 164 kg of BW. On average, 5.5% of gross energy
      from SF was released as CH(4) in veal calves, which is similar to reported values
      in cattle fed only SF. In conclusion, the provision of low-protein SF resulted in
      improved N utilization for protein gain, particularly toward the end of the
      fattening period. In heavy calves, recycling of urea originating from amino acids
      in milk replacer potentially contributes substantially to the N retention of veal
      calves fed SF.

PMID- 22959941
TI  - Preference for pasture versus freestall housing by dairy cattle when stall
      availability indoors is reduced.
AB  - Providing cattle with access to pasture has been shown to yield benefits,
      including access to more space, fewer agonistic interactions, better air quality,
      and the ability to perform a greater range of normal behaviors. Preference for
      pasture appears to depend on several parameters, including weather conditions and
      availability of shade. The primary aim of this study was to evaluate the
      preference for pasture versus inside a freestall barn with variable stocking
      densities at the stalls. We also investigated the effect of temperature-humidity
      index (THI) and precipitation on this preference. Overall, cows spent on average
      13.7+/-2.6 h/d (mean +/- SD) on pasture (ranging from 7.2 to 18.0 h/d across
      days); at night (between 2000 and 0600 h) cows spent the majority of their time
      (78.5+/-27.8%) on pasture. Stall availability had no effect on time spent
      outside, but time spent on pasture decreased with increasing THI during the day
      and declined during nights with more rainfall. Stall usage changed depending on
      stall availability; standing with 2 and 4 feet in the stall and lying time
      indoors decreased with decreasing stall availability. Indoor lying time also
      increased with higher THI and more precipitation. In conclusion, cows preferred
      to be outside at night; they were much more likely to remain indoors during the
      day, even when overstocked.

PMID- 22959942
TI  - Short communication: genetic parameters for feed intake, production, and extent
      of negative energy balance in Nordic Red dairy cattle.
AB  - The aim of this paper was to study the genetic parameters for feed intake, milk
      production, and energy balance in Nordic Red dairy cattle from an experimental
      data set. The data were collected at the MTT Agrifood Research Finland Rehtijarvi
      experimental farm in 4 feeding trials between 1998 and 2008, and included
      lactation wk 2 to 30 for 291 Nordic Red nucleus heifers descending from 72
      different sires. The studied traits included weekly averages for energy-corrected
      milk yield (ECM, kg/d), dry matter intake (kg/d), body weight (BW, kg), body
      condition score (BCS, score 1 to 5), and energy balance (EB, MJ of metabolizable
      energy/d). The data were analyzed with both fixed and random regression models.
      The heritabilities of ECM and BCS were moderate to high and remained fairly
      constant over the entire lactation period, whereas the heritabilities of BW and
      EB were the highest in early lactation (0.47 and 0.37, respectively) and declined
      later on. The heritabilities of DMI were highest (0.33) around lactation wk 5 and
      again at lactation wk 30, and were somewhat lower at the beginning of the
      lactation and in the middle period. The genetic correlations between the traits
      differed considerably between early and later lactation periods, especially for
      the trait pairs ECM-dry matter intake, ECM-EB, BW-EB, and BCS-EB, being negative
      or close to zero in lactation wk 2 to 5 but turning moderate to strong and
      positive by lactation wk 10. The results suggest that the lactating cows express
      their genetic potential for feed intake and energy utilization most clearly
      between lactation wk 2 to 10. The best candidate trait for selection might be EB
      in lactation wk 2 to 5 because it has a moderate heritability and is not
      genetically correlated with BW or BCS in that period.

PMID- 22959943
TI  - Short communication: CSN1S1-CSN3 (alpha(S1)-kappa-casein) composite genotypes
      affect detailed milk protein composition of Mediterranean water buffalo.
AB  - The aim of the study was to investigate the effect of composite CSN1S1-CSN3
      [alpha(S1)-kappa-casein (CN)] genotype on milk protein composition in
      Mediterranean water buffalo. Content of alpha(S1)-CN, alpha(S2)-CN, beta-CN,
      gamma-CN, kappa-CN, glycosylated and unglycosylated kappa-CN, alpha-lactalbumin,
      and beta-lactoglobulin was measured by reversed-phase HPLC using 621 individual
      milk samples. Genotypes at CSN1S1 and CSN3 were also obtained by reversed-phase
      HPLC. Two alleles were detected at CSN1S1 (corresponding to the A and B variants,
      O62823: p.Leu193Ser,) and at CSN3 (corresponding to the X1 and X2 variants,
      CAP12622.1: p.Ile156Thr). Increased proportions of alpha(S1)-CN in total casein
      (TCN) were associated with genotypes carrying CSN1S1 A. Genotypes associated with
      a marked decrease of the proportion of alpha(S1)-CN in TCN (composite genotypes
      AB-X1X1 and BB-X1X2) were associated with marked increases in the proportion of
      alpha(S2)-CN. In addition, composite genotypes carrying the X1 allele at CSN3
      were associated with a greater proportion of alpha(S2)-CN in TCN relative to
      those carrying CSN3 X2. Composite genotypes greatly affected also the variability
      of ratios of kappa-CN to TCN, with genotypes carrying the X1 allele at CSN3 being
      associated with decreased ratios. The decreased content of glycosylated kappa-CN
      associated with CSN3 X1 was responsible for the overall lower content of total
      kappa-CN in milk of X1-carrying animals. Increasing the frequency of specific
      genotypes might be an effective way to alter milk protein composition, namely the
      proportion of alpha(S1)-CN, alpha(S2)-CN, and kappa-CN in TCN, and the degree of
      glycosylation of kappa-CN.

PMID- 22959944
TI  - Heat stability of micellar casein concentrates as affected by temperature and pH.
AB  - The increased interest in using micellar casein concentrates (MCC) obtained by
      microfiltration in the manufacture of shelf-stable high-protein beverages creates
      a need to understand the effect of sterilization treatments on the stability of
      this ingredient. The goals of this work were to (1) elucidate the effects of pH
      and heat treatment temperatures in the sterilization range on the stability of
      MCC, and (2) use the generated knowledge to develop solutions for stabilizing the
      MCC during sterilization treatments. Micellar casein concentrate powders were
      reconstituted, and the resulting casein dispersions were adjusted to pH values of
      6.5 to 7.3. Subsequently, the MCC samples were heated in an oil bath to 110 to
      150 degrees C. The treated samples were evaluated for particle size, soluble
      minerals, and casein dissociation. At pH <6.7, all heat-treated samples were
      visibly aggregated or coagulated. At pH 6.9, higher temperatures led to increased
      particle size, whereas at pH >6.9, few or no changes were observed after heat
      treatment. Casein dissociation increased with increasing pH for all caseins, at
      all temperatures, with dissociation of kappa-casein and beta-casein being the
      most pronounced. At higher pH, the levels of dissociated alpha(s)-casein
      decreased after heat treatment, suggesting aggregation of alpha(s)-casein in the
      presence of Ca and protection lost by kappa-casein. It was concluded that
      increased stability of MCC requires increasing the pH or lowering the processing
      temperature. After applying these modifications, MCC was submitted to both
      retorting and UHT sterilization, at equivalent lethality. A significant reduction
      in particle size was obtained and no coagulation or aggregation occurred after
      retorting or UHT under the modified conditions as compared with the controls. The
      knowledge generated in this study will allow the effective stabilization of MCC
      in practical applications, such as the production of high-protein, shelf-stable
      beverages.

PMID- 22959945
TI  - MicroRNA expression patterns in the bovine mammary gland are affected by stage of
      lactation.
AB  - The objective of this work was to determine the expression pattern of microRNA
      (miR) associated with cellular proliferation, lipid metabolism, and innate
      immunity in dairy cow mammary gland tissue at different stages of lactation. The
      expression of miR-10a, miR-15b, miR-16, miR-21, miR-31, miR-33b, miR-145, miR
      146b, miR-155, miR-181a, miR-205, miR-221, and miR-223 was studied by real-time
      reverse-transcription PCR in tissue (n=7/stage) harvested via repeated biopsies
      during the dry period (-30 d prepartum), the fresh period (7 d postpartum), and
      early lactation (30 d postpartum). Except for miR-31, all miR studied increased
      in expression between the dry and fresh periods. Among those upregulated, the
      expression of miR-221 increased further at early lactation, suggesting a role in
      the control of endothelial cell proliferation or angiogenesis, whereas the
      expression of miR-223 decreased at early lactation but to a level that was
      greater than in the dry period, suggesting it could play a role in the mammary
      response to pathogens soon after parturition. The expression of miR-31, a
      hormonally regulated miR that inhibits cyclin gene expression, was greater at
      early lactation compared with the dry period. From a metabolic standpoint, the
      consistent upregulation of miR-33b during early lactation compared with the dry
      period suggests that this miR may exert some control over lipogenesis in mammary
      tissue. Overall, results indicate that expression of miR associated with
      transcriptional regulation of genes across diverse biological functions is
      altered by stage of lactation. The specific roles of these miR during lactation
      will require further research.

PMID- 22959946
TI  - Short communication: simultaneous analysis of reducing sugars and 5-hydroxymethyl
      2-furaldehyde at a low concentration by high performance anion exchange
      chromatography with electrochemical detector, compared with HPLC with refractive
      index detector.
AB  - A simultaneous analysis of reducing sugars and 5-hydroxymethyl-2-furaldehyde of
      the Maillard reaction products was detailed. It was based on a high performance
      anion exchange chromatography with electrochemical detector system and an HPLC
      with refractive index detector. Results showed that high performance anion
      exchange chromatography with electrochemical detector using a CarboPac PA-1
      column (Dionex Corp., Sunnyvale, CA) was more suitable for reducing sugars and 5
      hydroxymethyl-2-furaldehyde determination, especially for trace analysis. The
      lowest detectable limit of reducing sugars and 5-hydroxymethyl-2-furaldehyde was
      0.00005 mol/L in this experiment. However, HPLC with a refractive index detector
      always produces a tailing peak for 5-hydroxymethyl-2-furaldehyde, and mannose and
      fructose cannot be absolutely separated. The results of the present study could
      provide a more sensitive means for 5-hydroxymethyl-2-furaldehyde and reducing
      sugar detection.

PMID- 22959947
TI  - Accuracy of in-line milk composition analysis with diffuse reflectance near
      infrared spectroscopy.
AB  - Knowledge of daily milk composition changes can assist in monitoring dairy cow
      health and can help to detect nutritional imbalances. An analytical tool offering
      the possibility of analyzing milk during the daily milking routine would provide
      such information. Near-infrared (NIR) spectroscopy can analyze multiple
      constituents in a given substrate at the same time. In this study, a special NIR
      in-line milk-analyzing device was designed, and its ability to predict the
      contents of fat, protein, lactose, and urea and the somatic cell count in milk
      during the milking process was evaluated. The NIR spectra were acquired with a
      diode array spectrometer in diffuse reflection in the wavelength range 851 to
      1649 nm. The spectra originated from a total of 785 partial milkings out of 84
      composite milkings. Corresponding subsamples of the composite milkings were used
      for reference analysis (n=785). Excellent validation results were obtained with
      regard to the coefficients of determination (R(2)=0.99, 0.98, and 0.92), and
      standard errors of prediction (0.09, 0.05, and 0.06) for fat (%), protein (%),
      and lactose (%), respectively. Satisfying results were achieved for urea content
      (mg/L) and logarithmically transformed SCC in milk, with R(2) of 0.82 and 0.85
      and standard errors of prediction of 19.3 and 0.18, respectively. The accuracy of
      predicting protein, lactose, and urea contents was in accordance with
      international recommendations for reproducibility specified for in-line
      analytical devices.

PMID- 22959948
TI  - Validation of handheld meters to measure blood L-lactate concentration in dairy
      cows and calves.
AB  - In cattle, blood lactate was measured in various conditions such as parturition
      and dystocia. To our knowledge, to date, no handheld device has been validated
      for the use in cows and only one handheld device was validated for the use in
      calves. When determining plasma lactate concentrations blood samples have to be
      processed carefully. Sodium fluoride was recommended to inhibit glycolysis and to
      stabilize plasma lactate concentrations during transport. However, its effect on
      measurements conducted with electrochemical meters has not been studied. The
      objectives of 3 experiments were to study factors influencing measures of L
      lactate in dairy cows (e.g., different anticoagulants, different methods) and to
      validate a handheld device (Lactate Scout, SensLab GmbH, Leipzig, Germany) to
      determine L-lactate concentration in dairy cows and calves. In a first approach,
      blood samples from 49 cows were analyzed by 2 different laboratories. Measures of
      L-lactate concentration were correlated between the different laboratories in
      both lithium heparin plasma (r=0.98) and sodium fluoride plasma (r=0.99). In a
      second approach, these samples were analyzed using 3 methods [Lactate Scout,
      Biosen C_line (EKF Diagnostics GmbH, Barleben, Germany), and commercial
      laboratory]. Concentrations of L-lactate measured in lithium heparin did not
      differ when analyzed with the Lactate Scout (0.99+/-0.35 mmol/L), the Biosen
      C_line (0.81+/-0.26 mmol/L), or the laboratory (1.0+/-0.36 mmol/L).
      Concentrations of L-lactate measured in sodium fluoride, however, were higher
      when analyzed with the Lactate Scout (1.85+/-0.66 mmol/L) compared with those
      measured with the Biosen C_line (0.92+/-0.37 mmol/L) and by the commercial
      laboratory (0.72+/-0.45 mmol/L). In the second and third experiments, blood
      samples from 173 cows and 106 calves were analyzed using the 3 methods (Lactate
      Scout, Biosen C_line, and commercial laboratory). L-Lactate concentrations
      measured with the 3 methods were correlated (cows: Lactate Scout vs. Biosen
      C_line: r=0.97, Lactate Scout vs. laboratory 1: r=0.98, Biosen C_line vs.
      laboratory 1: r=0.99; calves: Lactate Scout vs. Biosen C_line: r=0.97, Lactate
      Scout vs. laboratory 1: r=0.98, Biosen C_line vs. laboratory 1: r=0.99). In
      conclusion, Lactate Scout and Biosen C_line measure blood L-lactate
      concentrations reliably compared with a commercial laboratory as the reference
      method in dairy cows and calves. However, attention needs to be paid to the
      choice of anticoagulant used in sample collection.

PMID- 22959949
TI  - Prevention of oral mucositis in children receiving cancer therapy: a systematic
      review and evidence-based analysis.
AB  - This systematic review investigated, critically appraised, and rated the evidence
      on agents used to prevent oral mucositis in children. A comprehensive search of
      the relevant literature was performed up to December 2011. Articles were included
      according to the inclusion/exclusion criteria and were critically appraised for
      validation and quality assessment using a checklist consisting of 18 categories.
      Each article was then rated for its strength of evidence. 16,471 articles were
      retrieved from 19 different databases and then reduced to 27 articles that fit
      the inclusion criteria. Five articles on oral care protocols supported their use
      to prevent oral mucositis in children. Seven articles on chlorhexidine mouthwash
      and three on laser therapy had conflicting evidence of its use. The preventative
      agents that were supported by one or two articles included: benzydamine
      mouthwash, iseganan mouthwash, granulocyte-macrophage colony-stimulating factor
      (GM-CSF) mouthwash, oral/enteral glutamine, oral propantheline and cryotherapy,
      oral cryotherapy, oral sucralfate suspension, prostaglandin E2 tablets, and
      chewing gum. The reduction in the rates of occurrence of oral mucositis when
      using agents of fair (B) to good (A) evidence ranged from 22% to 52%. In
      conclusion, this review suggests the use of oral care protocols to prevent oral
      mucositis in children because of their strength of evidence (fair to good). The
      authors suggest avoiding agents with fair to good evidence against their use
      (oral sucralfate suspension, prostaglandin E2 tablets, and GM-CSF mouthwash).
      Agents with conflicting evidence (chlorhexidine mouthwash (used solely), laser
      therapy, and glutamine) should also be avoided until further research confirms
      their efficacy.

PMID- 22959951
TI  - [Advanced skin tumors of the face, what can we do?].

PMID- 22959950
TI  - Improvements to the Kunkel mutagenesis protocol for constructing primary and
      secondary phage-display libraries.
AB  - Site-directed mutagenesis is routinely performed in protein engineering
      experiments. One method, termed Kunkel mutagenesis, is frequently used for
      constructing libraries of peptide or protein variants in M13 bacteriophage,
      followed by affinity selection of phage particles. To make this method more
      efficient, the following two modifications were introduced: culture was incubated
      at 25 degrees C for phage replication, which yielded two- to sevenfold more
      single-stranded DNA template compared to growth at 37 degrees C, and restriction
      endonuclease recognition sites were used to remove non-recombinants. With both of
      the improvements, we could construct primary libraries of high complexity and
      that were 99-100% recombinant. Finally, with a third modification to the standard
      protocol of Kunkel mutagenesis, two secondary (mutagenic) libraries of a
      fibronectin type III (FN3) monobody were constructed with DNA segments that were
      amplified by error-prone and asymmetric PCR. Two advantages of this modification
      are that it bypasses the lengthy steps of restriction enzyme digestion and
      ligation, and that the pool of phage clones, recovered after affinity selection,
      can be used directly to generate a secondary library. Screening one of the two
      mutagenic libraries yielded variants that bound two- to fourfold tighter to human
      Pak1 kinase than the starting clone. The protocols described in this study should
      accelerate the discovery of phage-displayed recombinant affinity reagents.

PMID- 22959952
TI  - [Skin diversity: histological study of 140 skin residues, adapted to plastic
      surgery].
AB  - We present in this original article a histological study of surgical skin
      residues. AIM OF THE STUDY: This study was realized in order to show, in
      objective way, skin diversity according to sex, age and area, and to illustrate
      some current surgical practices of our speciality. PATIENTS AND METHOD: Two years
      along, 141 patients was selected, 69 Men and 72 women. Fifty-four biopsies were
      realized on the upper extremity, 34 on the trunk and 53 on legs and arms. The
      histological study was based on two steps; the first one was a classic
      quantitative study, with measurement of each cutaneous layer, and objective
      evaluation of elastic density in superficial dermis. The second one was a
      descriptive histological analysis of each cutaneous area. RESULTS: The results
      coming from the quantitative analysis, allowed us to establish a classification
      of all the areas, according to each parameter. These results are globally
      compliant to the literature. The results of the descriptive analysis, lead us to
      conclude that it exists a lot of different skins with regional specificities.
      Then the crossover of the two analyses allowed us to define good practices
      tricks, in order to choose the best reconstruction technique for each area.
      CONCLUSION: This study is just a rough draft of a dynamic skin cartography
      adapted to our surgery. But it allowed us to confirm our basic premise: it
      doesn't exist only one skin but many skins.

PMID- 22959953
TI  - Effect of protein release rates from tablet formulations on the immune response
      after sublingual immunization.
AB  - Dry vaccine formulations for sublingual administration would provide great
      advantages for public health use, especially in developing countries, since they
      are easy to administer and might also have improved stability properties. This
      study investigates the influence of protein release rate from mucoadhesive two
      layer tablets on the elicited antibody responses after sublingual immunization.
      Two fast release tablets, one based on a mixture of lactose and microcrystalline
      cellulose (MCC) and one protein coated ethylcellulose (EC) tablet, and three
      hydrophilic matrix tablets with extended release (ER) properties based on HPMC 90
      SH 100000 or Carbopol(r) 974-P NF were tested. The in vitro release profiles of
      the model protein ovalbumin (OVA) from these tablets were characterized and
      correlated to the in vivo potential of the tablets to induce an immune response
      after sublingual immunization in BALB/c mice. It could be concluded that a tablet
      with fast protein release elicits antibody titres not significantly different
      from titres obtained with OVA in solution, whereas low immune responses were
      observed with a slow release of OVA from the ER formulations. Thus, an ER tablet
      seems not favorable for vaccine delivery to the sublingual mucosa. Thus, we can
      present a fast releasing tablet formulation with attractive features for
      sublingual immunization, whereas the use of ER formulations for sublingual
      vaccination has to be investigated more in detail.

PMID- 22959955
TI  - In vivo evaluation of porous hydroxyapatite/chitosan-alginate composite scaffolds
      for bone tissue engineering.
AB  - Porous hydroxyapatite (HAp)/chitosan-alginate composite scaffolds were prepared
      through in situ co-precipitation and freeze-drying for bone tissue engineering.
      The composite scaffolds were highly porous and interconnected with a pore size of
      around 50-220 MUm at low concentrations of HAp. As the HAp content increased, the
      porosity of the scaffolds decreased from 84.98 to 74.54%. An MTT assay indicates
      that the obtained scaffolds have no cytotoxic effects on MG-63 cells, and that
      they have good biocompatibility. An implantation experiment in mouse skulls
      revealed that the composite scaffold provides a strong positive effect on bone
      formation in vivo in mice. Furthermore, that HAp/chitosan-alginate composite
      scaffold has been shown to be more effective for new bone generation than
      chitosan-alginate scaffold.

PMID- 22959956
TI  - Characterization of antioxidant-antimicrobial kappa-carrageenan films containing
      Satureja hortensis essential oil.
AB  - The present work was aimed at characterizing biodegradable composite kappa
      carrageenan films incorporated with Satureja hortensis (SEO) in terms of their
      physical, optical, mechanical, barrier and antioxidant properties. Also, in a
      comparative study, we sought to evaluate the antimicrobial effectiveness of these
      films against five pathogens. The films' water vapor barrier properties were
      found to improve considerably upon the addition of SEO. Carrageenan composite
      films were less resistant to breakage, more flexible and more opaque with lower
      gloss than the control film. These results can be explained by the film's
      microstructure, which was analyzed by atomic force microscopy and scanning
      electron microscopy. The films incorporating SEO showed good antioxidant
      properties; this effect was greatly improved when the proportion of added SEO was
      3%. Films with SEO effectively inhibited the five microorganisms tested. The
      results of the present study suggest that SEO as a natural antibacterial agent
      can potentially be used in packaging a wide range of food products, particularly
      those that are highly oxidative and microbial sensitive.

PMID- 22959954
TI  - Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid
      metabolites in humans.
AB  - Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in human
      diets, a major component of human tissues, and the direct precursor to the
      bioactive oxidized LA metabolites (OXLAMs), 9- and 13 hydroxy-octadecadienoic
      acid (9- and 13-HODE) and 9- and 13-oxo-octadecadienoic acid (9- and 13-oxoODE).
      These four OXLAMs have been mechanistically linked to pathological conditions
      ranging from cardiovascular disease to chronic pain. Plasma OXLAMs, which are
      elevated in Alzheimer's dementia and non-alcoholic steatohepatitis, have been
      proposed as biomarkers useful for indicating the presence and severity of both
      conditions. Because mammals lack the enzymatic machinery needed for de novo LA
      synthesis, the abundance of LA and OXLAMs in mammalian tissues may be modifiable
      via diet. To examine this issue in humans, we measured circulating LA and OXLAMs
      before and after a 12-week LA lowering dietary intervention in chronic headache
      patients. Lowering dietary LA significantly reduced the abundance of plasma
      OXLAMs, and reduced the LA content of multiple circulating lipid fractions that
      may serve as precursor pools for endogenous OXLAM synthesis. These results show
      that lowering dietary LA can reduce the synthesis and/or accumulation of oxidized
      LA derivatives that have been implicated in a variety of pathological conditions.
      Future studies evaluating the clinical implications of diet-induced OXLAM
      reductions are warranted.

PMID- 22959957
TI  - Phylogenetic analysis of dengue virus types 1 and 3 isolated in Jakarta,
      Indonesia in 1988.
AB  - Dengue viruses are mosquito-borne viruses that cause dengue fever and dengue
      hemorrhagic fever, both of which are globally important diseases. These viruses
      have evolved in a transmission cycle between human hosts and mosquito vectors in
      various tropical and subtropical environments. We previously isolated three
      strains of dengue type 1 virus (DENV1) and 14 strains of dengue type 3 virus
      (DENV3) during an outbreak of dengue fever and dengue hemorrhagic fever in
      Jakarta, Indonesia in 1988. Here, we compared the nucleotide sequences of the
      entire envelope protein-coding region among these strains. The isolates were 97.6
      100% identical for DENV1 and 98.8-100% identical for DENV3. All DENV1 isolates
      were included in two different clades of genotype IV and all DENV3 isolates were
      included in a single clade of genotype I. For DENV1, three Yap Island strains
      isolated in 2004 were the only strains closely related to the present isolates;
      the recently circulated Indonesian strains were in different clades. Molecular
      clock analyses estimated that ancestors of the genotype IV strains of DENV1 have
      been indigenous in Indonesia since 1948. We predict that they diverged frequently
      around 1967 and that their offspring distributed to Southeast Asia, the Western
      Pacific, and Africa. For DENV3, the clade containing all the present isolates
      also contained strains isolated from other Indonesian regions and other countries
      including Malaysia, Singapore, China, and East Timor from 1985-2010. Molecular
      clock analyses estimated that the common ancestor of the genotype I strains of
      DENV3 emerged in Indonesia around 1967 and diverged frequently until 1980, and
      that their offspring distributed mainly in Southeast Asia. The first dengue
      outbreak in 1968 and subsequent outbreaks in Indonesia might have influenced the
      divergence and distribution of the DENV1 genotype IV strains and the DENV3
      genotype I strains in many countries.

PMID- 22959958
TI  - Micro- and nano-spheres of low melting point metals and alloys, formed by
      ultrasonic cavitation.
AB  - Metals and alloys of low melting points (<430  degrees C) can be melted in hot
      silicone oil to form two immiscible liquids. Irradiation of the system with
      ultrasonic energy induces acoustic cavitation in the oil, which disperses the
      molten metals into microspheres that solidify rapidly upon cooling. This method
      has been applied to seven pure metals (Ga, In, Sn, Bi, Pb, Zn, Hg) and two
      eutectic alloys of gold (Au-Ge and Au-Si). The morphology and composition of the
      resulting microspheres were examined by SEM and EDS. Eutectic Au-Si formed also
      crystalline Au nanoparticles, which were separated and studied by HRTEM.

PMID- 22959959
TI  - Ultrasound assisted efficient conversion of aromatic aldehydes from oximes.
AB  - This work describes the ultrasound-assisted regeneration of aldehydes from oximes
      in ethanol and phosphoric acid as mediator of the reaction. The large scale
      regeneration of benzaldehyde was shown under similar conditions. The products
      were isolated in good yields after short reaction times under mild conditions.

PMID- 22959960
TI  - Proteomic identification of immunodominant chlamydial antigens in a mouse model.
AB  - Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen
      in the world. To identify new vaccine candidates a protein microarray was
      constructed by expressing the open reading frames (ORFs) from Chlamydia mouse
      pneumonitis (MoPn). C57BL/6, C3H/HeN and BALB/c mice were immunized either
      intranasally or intravaginally with live MoPn elementary bodies (EB). Two
      additional groups were immunized by the intramuscular plus subcutaneous routes
      with UV-treated EB, using CpG and Montanide as adjuvants to favor a Th1 response,
      or Alum, to elicit a Th2 response. Serum samples collected from the three strains
      of mice were tested in the microarray. The array included the expression of 909
      proteins from the 921 ORFs of the MoPn genome and plasmid. A total of 530 ORFs
      were recognized by at least one serum sample. Of these, 36 reacted with sera from
      the three strains of mice immunized with live EB. These antigens included
      proteins that were previously described as immunogenic such as MOMP and HSP60. In
      addition, we uncovered new immunogens, including 11 hypothetical proteins. In
      summary, we have identified new immunodominant chlamydial proteins that can be
      tested for their ability to induce protection in animal models and subsequently
      in humans.

PMID- 22959961
TI  - Reprogramming aging and progeria.
AB  - The aging rate of an organism depends on the ratio of tissue degeneration to
      tissue repair. As a consequence, molecular alterations that tip this balance
      toward degeneration cause accelerated aging. Conversely, interventions can be
      pursued to reduce tissue degeneration or to increase tissue repair with the aim
      of delaying the onset of age-associated manifestations. Recent studies on the
      biology of stem cells in aging have revealed the influence of systemic factors on
      their functionality and demonstrated the feasibility of reprogramming aged and
      progeroid cells. These results illustrate the reversibility of some aspects of
      the aging process and encourage the search for new anti-aging and anti-progeria
      interventions.

PMID- 22959962
TI  - Cellular reprogramming: a small molecule perspective.
AB  - The discovery that somatic cells can be reprogrammed to induced pluripotent stem
      cells (iPSCs) by the expression of a few transcription factors has attracted
      enormous interest in biomedical research and the field of regenerative medicine.
      iPSCs nearly identically resemble embryonic stem cells (ESCs) and can give rise
      to all cell types in the body, and thus have opened new opportunities for
      personalized regenerative medicine and new ways of modeling human diseases.
      Although some studies have raised concerns about genomic stability and epigenetic
      memory in the resulting cells, better understanding and control of the
      reprogramming process should enable enhanced efficiency and higher fidelity in
      reprogramming. Therefore, small molecules regulating reprogramming mechanisms are
      valuable tools to probe the process of reprogramming and harness cell fate
      transitions for various applications.

PMID- 22959964
TI  - Peripheral antinociceptive effect of anandamide and drugs that affect the
      endocannabinoid system on the formalin test in normal and streptozotocin-diabetic
      rats.
AB  - Diabetes is often associated with painful neuropathy. The current treatments are
      symptomatic and ineffective. Cannabinoids have been proposed as promising drugs
      for chronic pain treatment and its antinociceptive effect has already been
      related in nerve injury models of neuropathic pain, but little has been
      investigated in painful diabetic neuropathy models. Thus, the current study aims
      to investigate the potential antinociceptive effect of drugs that alter
      endocannabinoid system when injected subcutaneously into the dorsal surface of
      the ipsilateral hind paw in chemical hyperalgesia induced by formalin in both
      normoglycemic (Ngl) and streptozotocin-diabetic (Dbt) rats. Diabetic rats
      exhibited exaggerated flinching behaviors during first and second phases of the
      formalin test, indicating the presence of hyperalgesia. AM404, an anandamide
      (AEA) re-uptake inhibitor, AEA (an agonist of CB1/CB2 receptors) or ACEA (a
      selective CB1 receptor agonist) induced antinociception in both phases of
      formalin test in Ngl and Dbt rats. In both groups, the antinociceptive effect of
      ACEA was prevented by AM251, a CB1 inverse agonist while the antinociceptive
      effect of AEA was prevented by AM251 or AM630, a CB2 receptor antagonist. In Ngl
      rats, the antinociceptive effect of AM404 was prevented by AM251 or capsazepine
      only during first phase of the formalin test while in Dbt rats, this effect was
      blocked by pretreatment with AM251 (both phases) or AM630 (second phase). Taken
      together, these results demonstrated broad-spectrum antinociceptive properties of
      cannabinoids in a model of painful diabetic neuropathy. Peripheral activation of
      both cannabinoid receptors seems to mediate the antinociceptive effect of
      exogenous or endogenous anandamide.

PMID- 22959963
TI  - Nicotine-induced anxiety-like behavior in a rat model of the novelty-seeking
      phenotype is associated with long-lasting neuropeptidergic and neuroplastic
      adaptations in the amygdala: effects of the cannabinoid receptor 1 antagonist
      AM251.
AB  - A rat model of the novelty-seeking phenotype predicts vulnerability to the
      expression of behavioral sensitization to nicotine, where locomotor reactivity to
      novelty is used to screen experimentally-naive rats for high (HR) versus low (LR)
      responders. The present study examines the long-term neuropeptidergic and
      neuroplastic adaptations associated with the expression of locomotor
      sensitization to a low dose nicotine challenge and social anxiety-like behavior
      following chronic intermittent nicotine exposure during adolescence in the LRHR
      phenotype. Our data show that the expression of behavioral sensitization to
      nicotine and abstinence-related anxiety are detected in nicotine pre-exposed HRs
      even across a long (3 wks) abstinence. Moreover, these behavioral effects of
      nicotine are accompanied by a persistent imbalance between neuropeptide Y and
      corticotrophin releasing factor systems, and a persistent increase in brain
      derived neurotrophic factor (BDNF) and spinophilin mRNA levels in the amygdala.
      Furthermore, treatment with the cannabinoid receptor 1 antagonist, AM251 (5
      mg/kg) during a short (1 wk) abstinence is ineffective in reversing nicotine
      induced anxiety, fluctuations in BDNF and spinophilin mRNAs, and the
      neuropeptidergic dysregulations in the amygdala; although this treatment is
      effective in reversing the expression of locomotor sensitization to challenge
      nicotine even after a long abstinence. Interestingly, the identical AM251
      treatment administered during the late phase of a long abstinence further
      augments anxiety and associated changes in BDNF and spinophilin mRNA in the
      basolateral nucleus of the amygdala in nicotine pre-exposed HRs. These findings
      implicate long-lasting neuropeptidergic and neuroplastic changes in the amygdala
      in vulnerability to the behavioral effects of nicotine in the novelty-seeking
      phenotype.

PMID- 22959965
TI  - Caffeine increases mitochondrial function and blocks melatonin signaling to
      mitochondria in Alzheimer's mice and cells.
AB  - Caffeine and melatonin have been shown to protect the Swedish mutant amyloid
      precursor protein (APP(sw)) transgenic mouse model of Alzheimer's disease from
      cognitive dysfunction. But their mechanisms of action remain incompletely
      understood. These Alzheimer's mice have extensive mitochondrial dysfunction,
      which likely contributes to their cognitive decline. To further explore the
      mechanism through which caffeine and melatonin protect cognitive function in
      these mice, we monitored the function of isolated mitochondria from APP(sw) mice
      treated with caffeine, melatonin, or both in their drinking water for one month.
      Melatonin treatment yielded a near complete restoration of mitochondrial function
      in assays of respiratory rate, membrane potential, reactive oxygen species
      production, and ATP levels. Caffeine treatment by itself yielded a small increase
      in mitochondrial function. However, caffeine largely blocked the large
      enhancement of mitochondrial function provided by melatonin. Studies with N2a
      neuroblastoma cells stably expressing APP(sw) showed that specific inhibition of
      cAMP-dependent phosphodiesterase (PDE) 4 or cGMP-dependent PDE5 also blocked
      melatonin protection of mitochondrial function, but A(2a) and A1 adenosine
      receptor antagonists were without effect. Melatonin or caffeine at the
      concentrations used to modulate mitochondrial function in the cells had no effect
      on cAMP-dependent PDE activity or cellular cAMP or cGMP levels. Therefore,
      caffeine and increased cyclic nucleotide levels likely block melatonin signaling
      to mitochondria by independent mechanisms that do not involve adenosine receptor
      antagonism. The results of this study indicate that melatonin restores
      mitochondrial function much more potently than caffeine in APP(sw) transgenic
      mouse and cell models of Alzheimer's disease.

PMID- 22959966
TI  - Striatal interaction among dopamine, glutamate and ascorbate.
AB  - Despite evidence suggesting the interaction among glutamate (GLU), dopamine (DA)
      and ascorbic acid (AA) in the striatum, their actions are often studied
      separately. Microdialysis was used here to quantify the extracellular interaction
      among GLU-DA-AA in the striatum of rats, an interaction which was compared with
      those studied in the substantia nigra (SN). Perfusion of GLU by reverse
      microdialysis increased DA and decreased 3,4-dihydroxyphenylacetic acid (DOPAC)
      in the extracellular medium of the striatum, but increased both DA and DOPAC in
      the SN. The increase of extracellular DA-concentration induced by the local DA
      perfusion decreased the extracellular level of GLU and glutamine, an effect that,
      as suggested by the GLU and glutamine increase observed after the haloperidol
      administration, probably involves the D2 dopamine receptor. Local administration
      of AA increased the extracellular DA, decreased DOPAC and had no effect on GLU
      and glutamine. Present data suggest that, in the striatum, GLU-release inhibits
      DA-uptake, DA-release inhibits GLU-release, and AA-release prevents DA-oxidation
      increasing its extracellular diffusion. These effects were different in the SN
      where GLU probably promoted the DA-release instead of inhibiting the DA-uptake as
      presumably occurred in the striatum. Present data denote a marked GLU-DA-AA
      interaction in the striatum, which might be relevant for the pharmacological
      control of basal ganglia disorders.

PMID- 22959967
TI  - Evaluation of rapid training in ultrasound guided tourniquet application skills.
AB  - Tourniquet application has been widely accepted to improve survival for major
      limb trauma. Colour duplex ultrasound (US) can be used as a non-invasive method
      of confirming cessation of arterial flow. Participants with no or limited
      experience of ultrasound were taught to apply the Combat Application Tourniquet
      with ultrasound guidance. Following this, participants were tested in effective
      tourniquet application: Blind and with ultrasound guidance. US guidance improved
      abolition of limb perfusion from 22 to 93 per cent in upper limb; from 25 to 100
      per cent in lower limb (p=0.0027 and <0.0001). No significant difference was
      found in application time for the lower limb; less time was taken for application
      with US guidance in the upper limb 8.1 (7.1, 8.6) vs 4.5 s (4.0, 5.3; median
      (IQR)), p=0.002. Tourniquet ultrasound skills are rapidly acquired by novice
      operators. Accuracy improves with ultrasound guidance, this may have a role in
      improving survival.

PMID- 22959968
TI  - Laparoscopic adrenalectomy for co-secreting aldosterone and cortisol adenomas.
AB  - There are few published data on aldosterone and cortisol co-secreting adrenal
      tumours. Failure to perform comprehensive preoperative endocrine investigations
      in patients with adrenal "incidentalomas" or in those thought to be secreting
      only one hormone may account for this. Clinically patients with such lesions may
      have evidence of hypertension and hypokalaemia with no features of cortisol
      excess. Preoperative diagnosis of such lesions with accurate endocrinological
      work up is essential to prevent adrenal insufficiency and haemodynamic crises
      following removal of such glands. We present a series of 4 patients with co
      secreting tumours treated by laparoscopic adrenalectomy between September 2010
      and March 2011. Our experience suggests that dual secretors are more common than
      originally thought. A high index of suspicion and adequate endocrine work up is
      paramount in diagnosing such tumours and in experienced hands, laparoscopic
      adrenalectomy with appropriate substitutive steroid cover is safe, feasible and
      curative for these functioning adrenal tumours.

PMID- 22959969
TI  - Plasma Kisspeptin-54 levels in gastric cancer patients.
AB  - BACKGROUND: Kisspeptin (Kisspeptin-54; KP-54) is a 54-amino acid peptide was
      originally known as metastin that was implicated in suppression of tumor
      metastasis and circulating kisspeptin has been proposed as a tumor marker for
      numerous cancers in humans. However, the plasma level of KP-54 in gastric cancer
      (GC) remains undetermined. AIM: We aimed to investigate the plasma levels of KP
      54 in patients with GC. METHODS: Plasma KP-54 levels were quantified with enzyme
      immunoassay from blood samples of 40 patients with GC at their initial staging
      and 59 age-matched controls. RESULTS: Plasma KP-54 levels were significantly
      higher in GC patients (63.3+/-17.9) than in controls (49.0+/-12.7) (p=0.000). Cut
      off value for KP-54 was determined as 44 ng/ml and sensitivity, specificity,
      positive predictive value and negative predictive value, were 60%, 78%, 63%, and
      74% respectively. Plasma KP-54 levels were not correlated with any
      clinicopathological features of GC patients (p>0.05). CONCLUSIONS: Result of our
      preliminary study suggest that plasma KP-54 levels might be a useful parameter in
      diagnosis of GC.

PMID- 22959970
TI  - Peripheral vascular injuries due to blunt trauma (road traffic accident):
      management and outcome.
AB  - BACKGROUND: The present study was undertaken to analyze the pattern, presentation
      and management of peripheral vascular injuries due to road traffic accidents
      (RTA). METHODS: A prospective study of patients of peripheral vascular injuries
      due to road traffic accidents (RTA) between Jan. 2007 to Dec. 2011. A total of
      192 patients presented with peripheral vascular injuries due to RTA during this
      period. All patients with vascular injury due to other causes were excluded from
      study. RESULTS: Most of the patients were managed by reverse saphenous vein graft
      followed by end to end anastomosis. Most of the patients had associated long bone
      fractures. Delayed presentation and associated long bone fractures had bad effect
      on outcome. Wound infection and thrombosis of the graft were the most important
      complication. Amputation rate was 4.68%. CONCLUSION: Vascular injury due to RTA
      requires prompt recognition and referral to a vascular center. Immediate
      revascularization has excellent results and less morbidity. Proper clinical
      examination and hand held Doppler examination are enough to reach the diagnosis.

PMID- 22959971
TI  - Mechanistic studies of the role of a conserved histidine in a mammalian polyamine
      oxidase.
AB  - Polyamine oxidases are peroxisomal flavoproteins that catalyze the oxidation of
      an endo carbon nitrogen bond of N1-acetylspermine in the catabolism of
      polyamines. While no structure has been reported for a mammalian polyamine
      oxidase, sequence alignments of polyamine oxidizing flavoproteins identify a
      conserved histidine residue. Based on the structure of a yeast polyamine oxidase,
      Saccharomyces cerevisiae Fms1, this residue has been proposed to hydrogen bond to
      the reactive nitrogen in the polyamine substrate. The corresponding histidine in
      mouse polyamine oxidase, His64, has been mutated to glutamine, asparagine, and
      alanine to determine if this residue plays a similar role in the mammalian
      enzymes. The kinetics of the mutant enzymes were examined with N1-acetylspermine
      and the slow substrates spermine and N,N'-dibenzyl-1,4-diaminobutane. On average
      the mutations result in a decrease of ~15-fold in the rate constant for amine
      oxidation. Rapid-reaction kinetic analyses established that amine oxidation is
      rate-limiting with spermine as substrate for the wild-type and mutant enzymes and
      for the H64N enzyme with N1-acetylspermine as substrate. The k(cat)/K(O(2)) value
      was unaffected by the mutations with N1-acetylspermine as substrate, but
      decreased ~55-fold with the two slower substrates. The results are consistent
      with this residue assisting in properly positioning the amine substrate for
      oxidation.

PMID- 22959973
TI  - Novel haemoglobin mutation (alpha127Lys->Glu) increases oxygen affinity and has a
      minor effect on haptoglobin binding.
AB  - OBJECTIVES: To determine if a new haemoglobin (Hb) variant was the underlying
      cause of erythrocytosis in a subject with a high apparent HbA(1)c. DESIGN AND
      METHOD: Haemolysate was analysed by ESI MS, and individual components purified by
      ion exchange and reverse phase chromatography. Peptide mapping was used to
      pinpoint the substitution and DNA sequencing to confirm the precise mutation.
      Oxygen affinity was measured and relative haptoglobin (Hp) binding estimated.
      RESULTS: Intact protein analysis and peptide mapping suggested a mutation in
      peptide alpha13 and DNA sequencing confirmed a novel alpha127Lys->Glu
      substitution in the alpha 2 gene. The abnormal Hb had a significantly higher O(2)
      affinity (5.8 mmHg) than HbA (12.4 mmHg). In addition the mutation caused a small
      but significant decrease in Hp binding. CONCLUSION: Molecular models show that
      the side chain of alpha127Lys stabilises the T structure of deoxy Hb and that
      mutation to Glu would favour conversion to the high affinity R state.
      Notwithstanding this and the demonstrated high affinity, there was only a small
      increase in RBCs, Hb concentration and PCV in other female carriers of the
      mutation. The absence of a significant phenotype of erythrocytosis is most
      probably due to the low level (19%) of the variant.

PMID- 22959972
TI  - Crystal structure of the N-terminal domain of Nup358/RanBP2.
AB  - Key steps in mRNA export are the nuclear assembly of messenger ribonucleoprotein
      particles (mRNPs), the translocation of mRNPs through the nuclear pore complex
      (NPC), and the mRNP remodeling events at the cytoplasmic side of the NPC.
      Nup358/RanBP2 is a constituent of the cytoplasmic filaments of the NPC specific
      to higher eukaryotes and provides a multitude of binding sites for the
      nucleocytoplasmic transport machinery. Here, we present the crystal structure of
      the Nup358 N-terminal domain (NTD) at 0.95A resolution. The structure reveals an
      alpha-helical domain that harbors three central tetratricopeptide repeats (TPRs),
      flanked on each side by an additional solvating amphipathic alpha helix. Overall,
      the NTD adopts an unusual extended conformation that lacks the characteristic
      peptide-binding groove observed in canonical TPR domains. Strikingly, the vast
      majority of the NTD surface exhibits an evolutionarily conserved, positive
      electrostatic potential, and we demonstrate that the NTD possesses the capability
      to bind single-stranded RNA in solution. Together, these data suggest that the
      NTD contributes to mRNP remodeling events at the cytoplasmic face of the NPC.

PMID- 22959974
TI  - Expression of synovial fluid and articular cartilage VIP in human osteoarthritic
      knee: a new indicator of disease severity?
AB  - OBJECTIVES: Vasoactive intestinal peptide (VIP) is a molecule shared by the
      neuroendocrine immune network and is considered to be a potential candidate for
      treatment of inflammatory and autoimmune diseases. Although some recent studies
      demonstrate that VIP has a protective role in animal RA models, its variant in
      different disease grade of OA remains uncertain. DESIGN AND METHODS: Fifty
      patients with primary knee OA and ten controls with severe trauma were enrolled.
      Synovial fluid and articular cartilage samples were collected from specimens of
      total knee arthroplasty (TKA) or knee above amputation. VIP levels in these
      samples were assessed by ELISA and immunohistochemistry. Kellgren-Lawrence
      criteria and Mankin score were taken to determine the disease severity. RESULTS:
      Compared to the controls, OA patients have lower VIP concentration in synovial
      fluid (659.70+/-112.79, 95%CI 579.01-740.38 vs 470.83+/-156.40, 95%CI 426.38
      515.28 pg/mL, P<0.001) and articular cartilage (0.26+/-0.02, 95%CI 0.24-0.28 vs
      0.20+/-0.04, 95%CI 0.18-0.21, P<0.001). Subsequent analysis show that the VIP
      expression in synovial fluid is markedly correlated with its OD in articular
      cartilage (Pearson's r=0.580, P<0.001). Furthermore, the synovial fluid and
      articular cartilage levels of VIP both demonstrated to be negatively correlated
      with severity of disease (Spearman's rho=0.838, P<0.001; Spearman's rho=0.814,
      P<0.001). CONCLUSIONS: VIP in synovial fluid and articular cartilage is
      negatively associated with progressive joint damage in OA and is a potential
      indictor of disease severity.

PMID- 22959975
TI  - Human plasma paraoxonase 1 (PON1) arylesterase activity during aging: correlation
      with susceptibility of LDL oxidation.
AB  - BACKGROUND AND AIMS: The role of free radicals has long been proposed as a cause
      for the aging process. Oxidative stress is considered a major factor for altering
      many physiological processes and enzymatic activities during aging and is also
      known to play a major role in the development of several age-dependent diseases.
      Paraoxonase 1 (PON1) is an anti-atherosclerotic enzyme that mainly prevents
      accumulation of lipoperoxides and inhibits the lipid oxidation in low-density
      lipoproteins (LDL). This study was undertaken to investigate the antioxidant
      behavior of PON1 by measuring its arylesterase activity. The susceptibility of
      LDL for oxidation and the radical scavenging activity of plasma were also
      measured during aging in humans. METHODS: Arylesterase activity of PON1 was
      measured in plasma of human subjects between 20 and 81 years of age of both
      genders. The susceptibility of LDL for oxidation and radical scavenging activity
      were measured in plasma. RESULTS: Decrease in plasma arylesterase activity of
      PON1, increase in susceptibility of LDL for oxidation and decrease in plasma
      radical scavenging activity were observed as a function of human age.
      CONCLUSIONS: The study provides evidence of a relationship between PON1 activity,
      LDL oxidation and free radical scavenging activity of plasma. The present results
      emphasize the dependency of PON1 activity to prevailing oxidative stress during
      human aging. Our findings assume significance in view of the possible
      categorization of PON1 as a longevity gene.

PMID- 22959976
TI  - Population-based risk factors for elevated alanine aminotransferase in a South
      Texas Mexican-American population.
AB  - BACKGROUND AND AIMS: Elevated alanine aminotransferase (ALT >40 IU/mL) is a
      marker of liver injury but provides little insight into etiology. We aimed to
      identify and stratify risk factors associated with elevated ALT in a randomly
      selected population with a high prevalence of elevated ALT (39%), obesity (49%)
      and diabetes (30%). METHODS: Two machine learning methods, the support vector
      machine (SVM) and Bayesian logistic regression (BLR), were used to capture risk
      factors in a community cohort of 1532 adults from the Cameron County Hispanic
      Cohort (CCHC). A total of 28 predictor variables were used in the prediction
      models. The recently identified genetic marker rs738409 on the PNPLA3 gene was
      genotyped using the Sequenom iPLEX assay. RESULTS: The four major risk factors
      for elevated ALT were fasting plasma insulin level and insulin resistance,
      increased BMI and total body weight, plasma triglycerides and non-HDL
      cholesterol, and diastolic hypertension. In spite of the highly significant
      association of rs738409 in females, the role of rs738409 in the prediction model
      is minimal, compared to other epidemiological risk factors. Age and drug and
      alcohol consumption were not independent determinants of elevated ALT in this
      analysis. CONCLUSIONS: The risk factors most strongly associated with elevated
      ALT in this population are components of the metabolic syndrome and point to
      nonalcoholic fatty liver disease (NAFLD). This population-based model identifies
      the likely cause of liver disease without the requirement of individual
      pathological diagnosis of liver diseases. Use of such a model can greatly
      contribute to a population-based approach to prevention of liver disease.

PMID- 22959977
TI  - Microcapillary culture method: a novel tool for in vitro expansion of stem cells
      from scarce sources.
AB  - BACKGROUND AND AIMS: Although increasing numbers of studies report the derivation
      of stem cells from a variety of different tissues, derivation efficiencies
      greatly vary among different studies even for the same tissue source. Hence, a
      consistent and efficient isolation protocol has not yet been established to date.
      Several factors have so far been documented that influence and limit mesenchymal
      stem cell (MSC) isolation and cultivation, including the age and gender of the
      tissue donor, origin of the tissue, amount of sampled tissue material and cell
      culture characteristics including the choice of basal media, serum, gas
      composition, etc. The aim of the study was to investigate the microcapillary
      culture method (MCM) to establish an efficient and consistent isolation as well
      as cultivation protocol by comparing the results with other classic culture
      systems (flasks, center wells). METHODS: MSCs isolated from adipose tissue of
      different donors were observed comparatively under different culture systems
      (flasks, center wells, microcapillary tubes) and their proliferation and
      differentiation were investigated. Flow cytometry was used for immunophenotypic
      characterization of derived cells and histochemical staining (Oil Red O and
      Alizarin Red S) was applied for determining their differentiation capacity.
      RESULTS: It has been shown for the first time that AD-MSCs can consistently and
      efficiently be derived from a scarce amount of adipose tissue by MCM.
      CONCLUSIONS: Further and similar studies should be performed to determine whether
      this methodology can also be applicable for other MSC sources.

PMID- 22959979
TI  - The influence of preterm birth on the developing thalamocortical connectome.
AB  - INTRODUCTION: Defining connectivity in the human brain signifies a major
      neuroscientific goal. Advanced imaging techniques have enabled the non-invasive
      tracing of brain networks to define the human connectome on a millimetre-scale.
      During early development, the brain undergoes significant changes that are likely
      represented in the developing connectome, and preterm birth represents a
      significant environmental risk factor that impacts negatively on early cerebral
      development. Using tractography to comprehensively map the connections of the
      thalamocortical unit, we aim to demonstrate that premature extrauterine life due
      to preterm delivery results in significantly decreased thalamocortical
      connectivity in the developing human neonate. METHODS: T1- and T2-weighted
      magnetic resonance images and 32-direction diffusion tensor images were acquired
      from 18 healthy term-born neonates (median gestational age: 41(+3)) and 47
      preterm infants (median gestational age: 28(+3)) scanned at term-equivalent age.
      Using a novel processing pipeline for tracing connections in the neonatal brain
      we map and compare the thalamocortical macro-connectome between groups. RESULTS:
      We demonstrate that connections between the thalamus and the frontal cortices,
      supplementary motor areas, occipital lobe and temporal gyri are significantly
      diminished in preterm infants (FDR-corrected, p < .001). CONCLUSIONS: This
      supports the hypothesis that the thalamocortical system is vulnerable following
      preterm birth and the tractographic framework presented represents a method for
      analysing system connectivity that can be readily applied to other populations
      and neural systems.

PMID- 22959978
TI  - Going tobacco-free: predictors of clinician reactions and outcomes of the NY
      State Office of Alcoholism and Substance Abuse Services tobacco-free regulation.
AB  - In an effort to reduce patient tobacco dependence and create healthier work
      environments, New York State (NYS) mandated 100% tobacco-free addiction treatment
      programs for state funded or certified facilities in 2008. We present the results
      of a longitudinal study examining how local implementation features shape
      clinician reactions to the regulation and influence post-regulation clinician
      behavior and strain. A cohort of 147 clinicians associated with 13 treatment
      organizations throughout NYS completed a survey prior to the passage of the
      regulation and again approximately 1 year post-regulation. Findings reveal that
      local implementation features of clinician participation in the planning for
      change, the provision of change-related information, and perceived organizational
      support predicted perceptions of change management fairness, which in turn
      predicted clinical practice behaviors to support smoking cessation, as well as
      psychological and behavioral strain. In contrast, self-efficacy for change was
      neither related to local implementation nor clinician outcomes. Practical
      implications are discussed.

PMID- 22959980
TI  - Protective immunity against tick infestation in cattle vaccinated with
      recombinant trypsin inhibitor of Rhipicephalus microplus.
AB  - The cattle tick, Rhipicephalus microplus, is regarded as the most economically
      important ectoparasite of livestock globally. Control is achieved primarily
      through the use of acaricides. This approach is hampered by the development of
      resistance to commercial acaricides among cattle tick populations. Vaccination
      against R. microplus infestation is another technology that can be integrated for
      effective cattle tick control. Proteins belonging to the Kunitz-BPTI family are
      abundant in cattle tick salivary glands, midgut, and ovaries. These organs are
      attractive targets for the development of a novel cattle tick vaccine. Efficacy
      assessment against cattle tick infestation in bovines using a vaccine containing
      the recombinant form of a member of the Kunitz family from R. microplus produced
      in a yeast expression system is reported for the first time here. The yeast
      Pichia pastoris was bioengineered to produce the recombinant version of a trypsin
      inhibitor that is expressed in cattle tick larvae (rRmLTI). Immunization with
      rRmLTI afforded 32% efficacy against R. microplus. The estimated molecular weight
      of rRmLTI was 46 kDa. Structural homology to the native form of the larval
      trypsin inhibitor was documented by recognition of rRmLTI in Western-blots using
      polyclonal antibodies from mice immunized with cattle tick larval extract or
      rRmLTI. Bioinformatics analysis of the partial nucleotide and deduced amino acid
      sequences indicated that the rRmLTI closely resembles BmTI-6, which is a three
      headed Kunitz protein present in cattle tick ovary and fat tissue.

PMID- 22959981
TI  - Seroprevalence of seven high-risk HPV types in The Netherlands.
AB  - BACKGROUND: To obtain insight into the age-specific seroprevalence for seven high
      risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58)
      among the general population in the pre-vaccination era in The Netherlands.
      METHODS: From a cross-sectional population-based study (ISRCTN 20164309)
      performed in 2006/2007 6384 sera of men, women and children were tested for seven
      hr-HPV specific antibodies using a fluorescent bead-based multiplex immunoassay
      with virus-like particles of the seven HPV serotypes. RESULTS: An increase in
      seroprevalence was observed in adolescents, especially for the most prevalent HPV
      type 16 (up to 11.3%). The increase was most pronounced in women, but was less
      clear for the other six HPV serotypes. Relatively stable seroprevalences were
      found in the middle aged cohorts and a slight decrease in the elderly. For the
      age cohorts >14 years, the seroprevalence among women (25.2%) was higher compared
      with men (20.3%) (p=0.0002). We found that 10.1% of the population was
      seropositive for multiple HPV serotypes. CONCLUSIONS: The HPV vaccination program
      is targeted at preadolescents as is justified by the results in this study in
      which a step-up in HPV seroprevalence is observed at ages of sexual debut.
      Although direct interpretation of seroprevalence data are hampered by cross
      reactivity and seroconversion rate, these data are useful as baseline to evaluate
      long-term population effects of the HPV16/18 vaccination program.

PMID- 22959982
TI  - Enhanced immune response induced by a potential influenza A vaccine based on
      branched M2e polypeptides linked to tuftsin.
AB  - Vaccination is the most effective means for preventing influenza-associated
      morbidity and mortality. Since the influenza virus mutates frequently, the virus
      strains for new vaccine production should be changed according to predicted
      epidemic strains. The extracellular domain of matrix protein 2 (M2e) is 24 amino
      acids long, which is highly conserved and therefore a good target for the
      development of a universal vaccine which may protect against a much wider range
      of influenza A virus strains. However its low antigenicity and immunogenicity,
      which are related to its small size, poses a big challenge for vaccine
      development. Multiple antigen peptide system (MAP) is based on an inert core
      molecule of radially branching lysine dendrites onto which a number of peptide
      antigens are anchored. Tuftsin is an immuno-stimulant molecule peptide. Here we
      developed a novel peptide vaccine by connecting a tuftsin to a branched, four
      copy M2e. Not only did this increase the molecular mass, but also potentiate the
      immunogenicity. Two branched peptides, (M2e)4-tuftsin and (M2e)4-G4(tuftsin was
      replaced with four glycines), and a M2e monomer were synthesized using standard
      solid-phase methods. In vitro and in vivo studies were performed to compare their
      antigenicity and immunogenicity. Experiments in BALB/c mice demonstrated that the
      branched M2e could induce stronger humoral and cellular immune responses than the
      M2e monomer, and (M2e)4-tuftsin induced stronger humoral and cellular immune
      response than (M2e)4-G4. After lethal challenge with influenza virus PR8 strain,
      up to 80% of the animals in the (M2e)4-tuftsin vaccinated group still survived,
      in contrast to 44% in the (M2e)4-G4 group and 30% in the M2e monomer group. The
      combination of branched polypeptides and tuftsin in vaccine design is presented
      here for the first time, and the results show that the new construct is a
      promising candidate for a universal vaccine against the influenza A virus.

PMID- 22959983
TI  - Immune response to tetanus booster in infants aged 15 months born prematurely
      with very low birth weight.
AB  - OBJECTIVES: To compare humoral and cellular immune responses to tetanus booster
      vaccination in infants born prematurely with those born at full term and identify
      factors associated with the humoral response. METHODS: A prospective study was
      carried out on children born prematurely and with a birth weight <1500g and with
      infants born at full term. At 15 months (pre-vaccination) and 18 months (post
      vaccination), anti-tetanus antibodies were measured by ELISA; the intracellular
      interferon-gamma percentages of CD4+ T and CD8+ T cells after in vitro
      stimulation with tetanus toxoid were determined by flow cytometry. Chi-squared or
      Fisher's exact test was used to compare categorical variables. Student's t-test
      or Mann-Whitney test was used to compare numerical variables. Regression analysis
      was performed to determine factors associated with humoral immunity. Statistical
      significance was considered if p<0.05. RESULTS: Sixty-four premature and 54 full
      term infants were studied. The proportion of children immune against tetanus at
      15 and 18 months was similar in both groups. The geometric mean of the antibodies
      was lower among the premature children at 15 months (p=0.025) and was similar in
      both groups at 18 months (p=0.852). The percentages of CD4+ and CD8+ T cells
      expressing intracellular IFN-gamma were similar in both groups at 15 and 18
      months. Gestational age <32 weeks was associated with a reduction of -0.116IU/mL
      in the level of antibodies at 15 months. Breastfeeding >6 months was associated
      with a 3.5-fold greater chance of optimal protective (>=0.1IU/mL) antibody level
      against tetanus at 15 months and an increase of 0.956IU/mL in the level of
      antibodies at 18 months. CONCLUSIONS: Humoral and cellular response following a
      tetanus booster was similar in both groups. Premature infants exhibited lower
      levels of anti-tetanus antibodies at 15 months of age, with the lowest levels in
      those born at a gestational age of less than 32 weeks. Breastfeeding was
      associated with greater levels of antibody against tetanus.

PMID- 22959984
TI  - No effect of oral polio vaccine administered at birth on mortality and immune
      response to BCG. A natural experiment.
AB  - BACKGROUND: WHO recommends oral polio vaccine at birth (OPV0) in polio endemic
      countries. During a period without OPV in Guinea-Bissau in 2004, we observed that
      not receiving OPV0 was associated with significantly decreased mortality in boys
      and better immune response to BCG vaccination. In 2007, whilst conducting a trial
      of BCG and vitamin A supplementation (VAS) at birth to low birthweight (LBW)
      children, OPV was again lacking for a short period. We used this natural
      experiment to test the previous observations. METHODS: In the trial LBW infants
      were randomised to early or delayed BCG and VAS or placebo at birth. We noted
      whether the children received OPV0 or not. We compared children who received No
      OPV0 with those who received OPV0 in the 2 months before and the 2 months after
      the period without OPV. Mortality was compared in Cox regression models providing
      adjusted hazard ratios (aHR); the immune response to BCG was assessed in Poisson
      models providing adjusted prevalence ratios (aPR). RESULTS: Ninety-nine children
      received No OPV0 and were compared with 243 children who received OPV0. No OPV0
      was associated with insignificantly higher mortality during the first year of
      life, the aHR being 1.83 (95% CI: 0.93-3.61). The effect was similar in boys and
      girls. Overall, there was no significant association between No OPV0 and having a
      positive PPD response (aPR=1.33 (0.64-2.78)) or a scar (aPR=1.02 (0.93-1.11))
      after BCG vaccination, though No OPV0 boys were more likely to develop a scar
      (aPR: 1.10 (1.01-1.20)). CONCLUSIONS: The findings did not support our previous
      observation that not receiving OPV0 was associated with reduced mortality in
      boys. The findings weakly supported that OPV0 leads to a dampened response to
      simultaneously administered BCG vaccine in boys.

PMID- 22959985
TI  - A virus-like particle vaccine for coxsackievirus A16 potently elicits
      neutralizing antibodies that protect mice against lethal challenge.
AB  - Coxsackievirus A16 (CVA16) is one of the main causative agents of hand, foot and
      mouth disease (HFMD), which has been prevalent in the Asia-Pacific region over
      the last several years. However, no vaccine is yet available to prevent HFMD.
      Here we report the development of a virus-like particle (VLP) based experimental
      CVA16 vaccine. CVA16 VLPs were produced in insect cells by co-expression of the
      P1 and 3CD proteins of CVA16 using recombinant baculoviruses. Biochemical and
      biophysical analyses showed that CVA16 VLPs consisted of processed VP0, VP1 and
      VP3, and were present as ~ 30 nm spherical particles. Immunization with VLPs
      potently elicited CVA16-specific serum antibody responses in mice. Anti-VLP sera
      strongly neutralized in vitro both the homologous and heterologous strains of
      CVA16. More importantly, passive immunization with anti-VLP sera conferred
      protection against lethal CVA16 challenge in neonate mice, indicating a humoral
      mechanism of protection. Collectively, our results represent a successful first
      step toward the development of a safe and effective vaccine against CVA16
      infection.

PMID- 22959986
TI  - Measles, mumps, and rubella virus vaccine (M-M-RTMII): a review of 32 years of
      clinical and postmarketing experience.
AB  - M-M-RTMII (measles, mumps, and rubella virus vaccine live; Merck, Sharp, & Dohme
      Corp.) is indicated for simultaneous vaccination against measles, mumps, and
      rubella in individuals >= 12 months of age. Before the vaccine era, these viruses
      infected most exposed individuals, with subsequent morbidity and mortality. One
      of the greatest achievements of public health has been to eliminate these 3
      diseases in large geographic areas. The safety profile of M-M-RTMII is described
      using data from routine global postmarketing surveillance. Postmarketing
      surveillance has limitations (including incomplete reporting of case data), but
      allows collection of real-world information on large numbers of individuals, who
      may have concurrent medical problems excluding them from clinical trials. It can
      also identify rare adverse experiences (AEs). Over its 32-year history, ~ 575
      million doses of M-M-RTMII have been distributed worldwide, with 17,536 AEs
      voluntarily reported for an overall rate of 30.5 AEs/1,000,000 doses distributed.
      This review provides evidence that the vaccine is safe and well-tolerated.

PMID- 22959987
TI  - Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12
      years in highly endemic areas in China.
AB  - OBJECTIVE: To evaluate the long-term efficacy and duration of yeast-derived
      recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas. METHOD:
      A cross-sectional investigation was carried out in five HBV-endemic areas.
      Children who were born between 1997 and 2008 and vaccinated with yeast-derived
      recombinant hepatitis B vaccine were selected. Serum samples were taken to test
      HBV infection markers by microparticle enzyme immunoassay, and the results were
      compared to those before vaccination. RESULTS: 7066 subjects were enrolled. The
      average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV
      core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(
      )&Anti-HBc(-)&Anti-HBs(+) was 61.34%. With time after immunization, the
      percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric
      mean concentration (GMC) of anti-HBs decreased significantly annually. The
      portion of GMC=100-999.9 mIU/ml was 48.0% in 2008, and decreased to 16.7% in
      1997. CONCLUSION: HBsAg prevalence decreased dramatically. This shows that the
      yeast-derived recombinant hepatitis B vaccine is effective and stable after being
      used for 12 years in HBV-endemic areas. It is not suggested to carry out booster
      immunization.

PMID- 22959988
TI  - Effect of the vaccination scheme on PregSure(r) BVD induced alloreactivity and
      the incidence of Bovine Neonatal Pancytopenia.
AB  - Bovine Neonatal Pancytopenia (BNP) is a new neonate-maternal incompatibility
      phenomenon caused by vaccine-induced, maternal alloantibodies. The syndrome
      affects newborn calves at the approximate age of ten days and is characterized by
      spontaneous bleeding, severe anemia with an almost complete destruction of the
      red bone marrow. During the past two years the causal role of bioprocess
      impurities in PregSure((r))BVD, a strongly adjuvanted, inactivated vaccine
      against Bovine Virus Diarrhoea (BVD), in the induction of BNP causing
      alloantibodies has clearly been established. Despite intensive research efforts
      that have elucidated the basic principles of the BNP immunopathology still a
      number of questions remain open. In the current manuscript we address the
      puzzling observation that BNP incidences vary widely between different regions:
      as an example we compare the BNP incidences in the German Federal States of
      Bavaria and Lower Saxony. In Bavaria the BNP-incidence reaches 100 cases per
      100,000 doses PregSure((r))BVD, while in Lower Saxony the incidence is as low as
      6 cases per 100,000 doses. In Bavaria the vaccine has always been used according
      to the instructions for use. By contrast, in Lower Saxony BVD-immunization was
      performed according to a two-step vaccination protocol including a first
      immunization with an inactivated BVD-vaccine followed by booster immunizations
      with a live-attenuated BVD-vaccine. As a consequence, those cattle that received
      PregSure((r))BVD received in general more than two doses in Bavaria, while in
      Lower Saxony cows received at maximum one dose. By experimental immunization we
      can show that the two-step regimen including PregSure((r))BVD as a priming
      vaccine results in significantly lower alloantibody titers as compared to
      repetitive immunizations with the inactivated vaccine. The lower alloantibody
      titer after two-step vaccination explains the lower BNP-incidence in Lower Saxony
      and - generally speaking - indicates that variations in the vaccination regimen
      have a great influence on the induction of adverse reactions through bioprocess
      impurities.

PMID- 22959989
TI  - Phase II, dose ranging study of the safety and immunogenicity of single dose West
      Nile vaccine in healthy adults >= 50 years of age.
AB  - INTRODUCTION: ChimeriVax-WN02 is a live, attenuated chimeric vaccine for
      protection against West Nile virus (WNV) produced by insertion of the genes
      encoding the pre-membrane (prM) and envelope (E) proteins of WNV (strain NY99)
      into the yellow fever 7D vaccine virus. This Phase II, randomized, double-blind,
      placebo-controlled, multi-center study in the US assessed the immunogenicity,
      viremia, and safety of the ChimeriVax-WN02 vaccine. METHODS: The study included
      adults in general good health. Subjects aged >= 50 years were randomized to one
      of four treatment groups: ChimeriVax-WN02 4 * 10(3) plaque-forming units (pfu)
      (n=122), 4 * 10(4)pfu (n=124), 4 * 10(5)pfu (n=113), or placebo (n=120). A subset
      of subjects was randomized to assess viremia after vaccination at three different
      dose levels. Subjects were followed for safety up to 6 months after vaccination.
      RESULTS: A total of 121 subjects for WN024 * 10(3), 122 for WN02 4 * 10(4), 110
      for WN02 4 * 10(5), and 120 for the placebo group completed the study up to the 6
      month safety follow-up. Seroconversion, as measured by plaque reduction
      neutralization test (PRNT), was achieved at Day 28 by 92.1%, 93.2%, and 95.4% of
      subjects in the WN02 4 * 10(3), the WN02 4 * 10(4), and the WN02 4 * 10(5)
      groups, respectively. Viremia was transient, detected between Days 2 and 14 but
      not at Day 28, and in most cases did not reach the quantification threshold. The
      percentage of subjects reporting at least one event of reactogenicity was similar
      in the placebo and active vaccine groups and showed no dose relationship.
      CONCLUSIONS: The ChimeriVax-WN02 vaccine was highly immunogenic and well
      tolerated among subjects >= 50 years old at all dose levels.

PMID- 22959990
TI  - Monitoring of rotavirus vaccination in Morocco: establishing the baseline burden
      of rotavirus disease.
AB  - BACKGROUND: Rotavirus is a leading cause of childhood morbidity and mortality
      worldwide. Clinical trials for two rotavirus vaccines recommended by the WHO for
      global use since 2009 have successfully demonstrated the safety and efficacy of
      these vaccines in a wide range of countries. To control the burden of severe and
      fatal diarrheal disease, the Ministry of Health of Morocco introduced the single
      strain rotavirus vaccine into their national immunization program in 2010.
      METHODS: We employed a standard WHO case definition to identify children under 5
      hospitalized with AGE at four hospitals from June 2006 to May 2010 to establish
      baseline burden of rotavirus disease before introduction of vaccine. Stool
      samples were collected and tested for rotavirus using a standard enzyme
      immunoassay. RESULTS: Overall, 40% (741 of 1841) of the children hospitalized
      with AGE tested positive for rotavirus, making it the single most common cause of
      severe gastroenteritis among children in Morocco. Applying this prevalence to the
      estimates of diarrheal hospitalizations and deaths in Morocco, we estimate that
      rotavirus annually causes 19,646 hospitalizations and 1604 deaths in children
      under 5 years of age. DISCUSSION: On the basis of these surveillance data, we
      estimate that 1 in 389 Moroccan children died and 1 in 32 was hospitalized due to
      rotavirus before their fifth birthday. A considerable proportion of these deaths
      and hospitalizations should be preventable through vaccination, and the 4 years
      of stable prevaccine surveillance in Morocco will be a tremendously useful
      platform for assessing potential changes in the epidemiology of rotavirus disease
      and measuring impact of the new rotavirus vaccine program in Morocco.

PMID- 22959991
TI  - A nanosized delivery system of superparamagnetic iron oxide for tumor MR imaging.
AB  - Superparamagnetic iron oxide (SPIO) nanoparticles have been intensively
      investigated as MRI probes due to the noninvasive detection of in vivo
      pathological changes. In the study, a nanosized system for SPIO delivery to a
      tumor was prepared to overcome the common challenges of SPIO nanoparticles such
      as insufficient uptake of SPIO by specific cells due to instability, short half
      life by macrophage, and low efficiency of internalization. SPIO with ca. 6 nm
      sizes as a MRI probe and PLA-PEG (5K-2K) as a biocompatible stable system were
      prepared. The hydrophobic modified SPIO were loaded into the core of micelles and
      showed a stable dispersion with 140-170 nm particle sizes. The SPIO loading
      micelles showed higher relaxivity coefficients and increases of T(2) relaxation
      in vivo MR imaging. This SPIO delivery system with high stability and sensitivity
      can be a promising imaging formulation as MRI T(2) probes for tumor detection.

PMID- 22959992
TI  - Sustained in vitro release and cell uptake of doxorubicin adsorbed onto gold
      nanoparticles and covered by a polyelectrolyte complex layer.
AB  - Gold nanoparticles functionalized with doxorubicin and stabilized with
      multilayers of degradable polyelectrolyte were allowed to age in aqueous medium
      in vitro in order to show the possibility of drug release in cellular
      environment. The chemico-physical characteristics of the nanoparticles are
      reported. The observed release of doxorubicin (DOX) was pH-dependent, and it
      increased in acidic environment. Cell uptake of nanoparticles and drug release
      were monitored by laser scanning confocal microscopy. Data showed that drug
      bearing nanoparticles delivered DOX into the nuclei of A549 cells, leading to
      pronounced cytotoxic effects to this lung tumor cells. Our results suggest that
      gold nanoparticles conjugated with doxorubicin could be used as a pH-triggered
      drug releasing carrier for tumor drug delivery.

PMID- 22959993
TI  - Preparation of polymeric particles in CO(2) medium using non-toxic solvents:
      formulation and comparisons with a phase separation method.
AB  - The aim of this work was to elaborate formulation strategies to encapsulate a
      protein into biodegradable polymeric particles for sustained release purpose. In
      this paper, two encapsulation methods will be presented, one dealing with a phase
      separation phenomenon while the other involving an emulsification/extraction
      process in CO(2) medium. In those methods, only non-volatile injectable solvents
      such as glycofurol or isosorbide dimethyl ether were used to dissolve the
      polymer. Moreover, experimental designs were built up to help us to go further in
      the understanding of the processes and to better predict output responses in
      design space. Spherical particles were successfully generated with a satisfactory
      encapsulation yield. Further characterization steps such as in vitro, in vivo
      releases will be carried out to validate the interest of our encapsulation
      methods in the development of drug delivery systems.

PMID- 22959994
TI  - Immuno EM-OM correlative microscopy in solution by atmospheric scanning electron
      microscopy (ASEM).
AB  - In the atmospheric scanning electron microscope (ASEM), an inverted SEM observes
      the wet sample from beneath an open dish while an optical microscope (OM)
      observes it from above. The disposable dish with a silicon nitride (SiN) film
      window can hold a few milliliters of culture medium, and allows various types of
      cells to be cultured in a stable environment. The use of this system for in situ
      correlative OM/SEM immuno-microscopy is explored, the efficiency of the required
      dual-tagged labeling assessed and the imaging capabilities of the ASEM
      documented. We have visualized the cytoskeletons formed by actin and tubulin, the
      chaperone PDI that catalyses native disulfide bond formation of proteins in the
      endoplasmic reticulum (ER) and the calcium sensor STIM1 that is integrated in ER
      membranes, using established cell lines. In particular, a dynamic string-like
      gathering of STIM1 was observed on the ER in Jurkat T cells in response to Ca(2+)
      store depletion. We have also visualized filamentous actin (F-actin) and tubulin
      in the growth cones of primary-culture neurons as well as in synapses. Further,
      radially running actin fibers were shown to partly colocalize with concentric
      bands of the Ca(2+) signaling component Homer1c in the lamellipodia of neuron
      primary culture growth cones. After synapse formation, neurite configurations
      were drastically rearranged; a button structure with a fine F-actin frame faces a
      spine with a different F-actin framework. Based on this work, ASEM correlative
      microscopy promises to allow the dynamics of various protein complexes to be
      investigated in the near future.

PMID- 22959995
TI  - Can we assess an acute myocardial infarction in patients with acute coronary
      syndrome according to diagnostic accuracy of heat shock proteins?
AB  - Heat shock proteins (HSPs) have changed very little with evolution, suggesting
      that they play important role(s) in cellular survival. Specifically, HSPs protect
      cells from induced cell death. Their expression is triggered by heat or other
      stress, such as ischemia. HSPs provide protection against protein denaturation,
      although they slightly differ with respect to group affiliation. Release of HSPs
      from necrotic and ischemic cardiomyocytes into the intercellular space and plasma
      may correlate with the intensity of the pro-inflammatory response observed during
      and immediately after myocardial infarction. We hypothesized that the plasma
      concentration of particularly inducible forms of HSPs from different groups (HSP
      90, HSP 70, HSP 60 and/or HSP 20) can be used as early specific markers for
      diagnosing myocardial infarction in patients with acute coronary syndrome. Our
      hypothesis is supported by the following data: (I) HSP expression occurs very
      early after acute coronary events; (II) HSP concentrations increase rapidly in
      the peripheral blood; (III) HSP concentrations correlate with markers of
      myocardial necrosis and pro-inflammatory biochemical parameters. The magnitude of
      the increase in plasma HSP concentrations over initial concentrations during the
      period of highest sensitivity and specificity of the assay could be important for
      early detection of myocardial infarction and distinguishing it from unstable
      angina. We suggest that these parameters, along with close observation of
      patients with chest pain, will assist providers who must differentiate between
      acute myocardial damage and other organ diseases.

PMID- 22959997
TI  - Enhancing drug compliance and the placebo effect by raising subjective
      expectations.
AB  - Increasing the patient's subjectively felt effectiveness of a treatment might be
      a key to enhanced drug compliance and placebo effects, and may in this way
      enhance the effectiveness of medical treatment at a low cost. Simple methods to
      achieve this aim are suggested, derived from consumer psychology, psychology of
      judgement and user-centered design. A drug's design should meet three criteria:
      an intuitive design which makes the purpose of the drug easily discernible,
      confirmatory side effects which give feedback that matches the drug's purpose,
      and mental models which enable the patient to develop an understanding of the
      drug's mechanism of action.

PMID- 22959996
TI  - Gliomas and seizures.
AB  - Glial neoplasms account for nearly 50% of all adult primary brain tumors. They
      originate from glial cells in the brain and/or spinal cord and include low-grade
      diffuse astrocytomas, anaplastic-astrocytomas, and glioblastomas. Of all brain
      tumors, glioblastoma multiforme (GBM) is the most aggressive and is characterized
      by rapid glial cell growth, resistance to radio- and chemo- therapies, and
      relentless infiltration and spreading throughout the central nervous system
      (CNS). In glioblastomas, primary tumor growth and CNS invasion are associated
      with the activation of complex structural molecular and metabolic changes within
      the tumor tissue, which profoundly affect the surrounding neuronal networks and
      may in part explain induction of epilepsy. In fact, epileptic seizures are very
      common among patients with glial tumors, reaching nearly 50% in glioblastoma
      patients and almost 90% in low-grade astrocytomas. The overall hypothesis
      presented here discusses the possibility that the aberrant tumor cell metabolism
      may act directly on neuronal network, and this leads to seizure susceptibility.
      Further invasion and growth of the malignant glial cells exacerbate this initial
      pathologic state which promotes recurrent seizures (epileptogenesis).

PMID- 22959998
TI  - Low dose, early mucosal exposure will minimize the risk of microbial disease.
AB  - In the 21st century we will rediscover the germ theory of disease: germs not only
      cause infection as described in standard textbooks but also have a pathogenic
      role in autoimmunity, atherosclerosis, cancer and even acute psychiatric
      conditions. In order to reduce morbidity and mortality caused by common organisms
      we should ensure that exposure is early, often, by the mucosal route and in low
      dose. Micro-organisms should be delivered daily throughout life by respiratory
      mucosal spray or enteric coated pill, in precise dose and in a predetermined
      schedule.

PMID- 22959999
TI  - Compartmental chest wall volume changes during volitional hyperpnoea with
      constant tidal volume in healthy individuals.
AB  - Prolonged high-intensity ventilation is associated with the development of rapid
      shallow breathing with decreased end-inspiratory volumes of all chest wall
      compartments. During respiratory muscle endurance training using normocapnic
      hyperpnoea, tidal volume (V(T)) is normally kept constant. The aim of this study
      was to investigate possible changes in muscle recruitment during constant-V(T)
      hyperpnoea, to assess potential mechanisms related to rapid shallow breathing.
      Ten healthy subjects performed 1h of normocapnic hyperpnoea at 70% of maximal
      voluntary ventilation. Chest wall volume changes were assessed by optoelectronic
      plethysmography. End-inspiratory (1.08 +/- 0.18 versus 0.96 +/- 0.27 l, p=0.017)
      and end-expiratory volumes (-0.13 +/- 0.15 versus -0.31 +/- 0.19 l, p=0.007) of
      the pulmonary ribcage decreased significantly and lung function and respiratory
      muscle strength were reduced (all p<0.05). Since with forced, constant V(T) only
      the inspiratory rib cage muscles were unable to sustain end-inspiratory volume of
      their compartment, inspiratory rib cage muscles are the most likely candidate
      responsible for the development of rapid shallow breathing.

PMID- 22960000
TI  - Detecting trends in tree growth: not so simple.
AB  - Tree biomass influences biogeochemical cycles, climate, and biodiversity across
      local to global scales. Understanding the environmental control of tree biomass
      demands consideration of the drivers of individual tree growth over their
      lifespan. This can be achieved by studies of tree growth in permanent sample
      plots (prospective studies) and tree ring analyses (retrospective studies).
      However, identification of growth trends and attribution of their drivers demands
      statistical control of the axiomatic co-variation of tree size and age, and
      avoiding sampling biases at the stand, forest, and regional scales. Tracking and
      predicting the effects of environmental change on tree biomass requires well
      designed studies that address the issues that we have reviewed.

PMID- 22960001
TI  - Thinking big: the effect of sexually objectifying music videos on bodily self
      perception in young women.
AB  - The present study investigated the effect of sexually objectifying music video
      exposure on young women's implicit bodily self-perception and the moderating role
      of self-esteem. Fifty-six college women of normal weight were either exposed to
      three sexually objectifying music videos or three neutral music videos. Perceived
      and ideal body size were measured both before and after video exposure, using
      horizontally stretched and compressed photographs of the participant's own body
      in swimming garment. As expected, only women low (but not high) in self-esteem
      were negatively affected by the sexually objectifying content of the music
      videos: they perceived themselves as bigger and showed an increased discrepancy
      between their perceived and ideal body size after video exposure. The neutral
      music videos did not influence women's bodily self-perceptions. These findings
      suggest that body image is a flexible construct, and that high self-esteem can
      protect women against the adverse effects of sexually objectifying media.

PMID- 22960002
TI  - Tuning the instability in static mode atomic force spectroscopy as obtained in an
      AFM by applying an electric field between the tip and the substrate.
AB  - We have investigated experimentally the role of cantilever instabilities in
      determination of the static mode force-distance curves in presence of a dc
      electric field. The electric field has been applied between the tip and the
      sample in an atomic force microscope working in ultra-high vacuum. We have shown
      how an electric field modifies the observed force (or cantilever deflection)-vs
      distance curves, commonly referred to as the static mode force spectroscopy
      curves, taken using an atomic force microscope. The electric field induced
      instabilities shift the jump-into-contact and jump-off-contact points and also
      the deflection at these instability points. We explained the experimental results
      using a model of the tip-sample interaction and quantitatively established a
      relation between the observed static mode force spectroscopy curves and the
      applied electric field which modifies the effective tip-sample interaction in a
      controlled manner. The investigation establishes a way to quantitatively evaluate
      the electrostatic force in an atomic force microscope using the static mode force
      spectroscopy curves.

PMID- 22960003
TI  - Atomic force microscope based biomolecular force-clamp measurements using a
      micromachined electrostatic actuator.
AB  - The authors describe a method for biomolecular force clamp measurements using
      atomic force microscope (AFM) cantilevers and micromachined membrane-based
      electrostatic actuators. The actuators comprise of Parylene membranes with
      embedded side actuation electrodes and are fabricated on a silicon substrate. The
      devices have a displacement range of 1.8 MUm with 200 V actuation voltage, and
      displacement uncertainty is 0.8 nm, including the noise and drift. The settling
      time, limited by the particular amplifier is 5 ms, with an inherent range down to
      20 MUs. A force clamp measurement setup using these actuators in a feedback loop
      has been used to measure bond life-times between human IgG and anti-human IgG
      molecules to demonstrate the feasibility of this method for biological
      experiments. The experimental findings are compared with a molecular pulling
      experiment and the results are found to be in good agreement.

PMID- 22960004
TI  - A phase I trial of tailored radiation therapy with concomitant cetuximab and
      cisplatin in the treatment of patients with cervical cancer: A gynecologic
      oncology group study.
AB  - BACKGROUND: Epithelial growth factor receptor over-expression correlates with
      poor outcomes in cervical cancer. This study assessed the safety of
      chemoradiation with cetuximab in the treatment of women with newly diagnosed
      locally advanced cervical cancer. METHODS: Patients received weekly cisplatin 30
      and 40 mg/m(2) [dose level (DL) 1 and 2] and cetuximab 400mg/m(2) loading dose
      and then 250 mg/m(2) for a total of six weeks with radiotherapy (RT). Patients
      with nodal metastases received extended field radiation therapy (EFRT). At the
      maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage,
      sequential design. RESULTS: In patients receiving pelvic RT, seven were treated
      at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3
      diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8
      weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there
      was one DLT (grade 4 CVA). Median RT duration was 50 days (range, 42-70). In
      patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis)
      and 24 in the feasibility phase with eight DLTs [delay in RT >8 weeks due to
      toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism,
      mucositis, mucositis with hypokalemia, pain with headache, and platelets with
      mucositis and headache]. Median EFRT duration was 56 days (range, 36-74).
      CONCLUSIONS: For patients receiving pelvic RT, cisplatin and cetuximab were
      feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was
      not feasible.

PMID- 22960005
TI  - Moore's Law: predictor and driver of the silicon era.

PMID- 22960006
TI  - DNA sensor based on vapour polymerised pedot films functionalised with gold
      nanoparticles.
AB  - Poly-3,4-ethylenedioxythiophene, PEDOT, films have been deposited on gold
      electrodes using polymerization from the vapor-phase in which the surface is
      first covered with a Fe (III) tosylate oxidant and then exposed to 3,4
      ethylenedioxythiophene, EDOT, vapor. Gold nanoparticles were then
      electrodeposited to give a nanocomposite material, PEDOT-AuNP. Thiolated capture
      strand DNA, that is complementary to the sequence associated with the pathogen S.
      aureus that causes mammary gland inflammation, was then immobilized onto the gold
      nanoparticles and the underlying gold electrode. The target oligo was then
      hybridized to the capture strand DNA. A probe strand, labeled with horse radish
      peroxidase, was then hybridized to the target. The concentration of the target
      was determined by measuring the current required to reduce hydroquinone oxidized
      during the regeneration of the HRP label. Semi-log plots of the pathogen DNA
      concentration vs. faradaic current are linear from 150 pM to 1 MUM and pM
      concentrations can be detected without the need for molecular, e.g., PCR or
      NASBA, amplification.

PMID- 22960007
TI  - Sensitive detection of rutin with novel ferrocene benzyne derivative modified
      electrodes.
AB  - A new ferrocene benzyne derivative (Fc-SAc) that contained oligo-(phenylene
      ethynylene) skeleton, ferrocene and thiolate terminal groups was firstly
      synthesized. The hydrolysis product of Fc-SAc (Fc-SH) was immobilized onto gold
      nanoparticles (AuNPs) modified glass carbon electrode (GCE) as sensing element
      for rutin detection with high sensitivity. The new sensing strategy was proposed
      by using two Fc-SH modified electrodes: Fc-S/AuNPs/GCE (Electrode1) and Fc
      S/AuNPs/graphene-chitosan/GCE (Electrode2). The electrochemical oxidation of
      rutin on Electrode2 was a diffusion-controlled process, which was different from
      a mass-controlled process on Electrode1. Under the optimal conditions, the peak
      currents of the sensors were linearly related to the concentrations of rutin. The
      linear responses ranges were 0.05-30 MUM and 0.04-100 MUM with the regression
      coefficients of 0.998 and 0.997 on Electrode1 and Electrode2, respectively.
      Electrode2 presented wider linear range, superior high sensitivity, lower
      detection limit and better stability on determination of rutin.

PMID- 22960008
TI  - Homogeneous immunoassays based on fluorescence emission intensity variations of
      zinc selenide quantum dot sensors.
AB  - The fluorescence emission intensity of ZnSe quantum dots (QDs) conjugated to
      proteins to form QD-based biomolecular sensors increases significantly upon
      binding of the sensors to target proteins in solution. This phenomenon enables
      the development of homogeneous, separation-free immunoassays for rapid
      quantitative detection of proteins in solution. Proof-of-principle assays were
      developed by dosing a solution containing a biomolecular target with a solution
      containing the corresponding QD-based sensor and monitoring the changes in the
      peak fluorescence emission intensity of the QDs. Direct immunoassays for
      detecting basic fibroblast growth factor (bFGF) and prostate-specific antigen
      (PSA) in solution were demonstrated using QD-anti-bFGF and QD-anti-PSA sensors. A
      competitive immunoassay for detecting human serum albumin (HSA) was also
      demonstrated by dosing samples containing HSA with QD-HSA sensors and free anti
      HSA antibodies. The QD-HSA sensors were tested in 1000* diluted human serum and
      found to be unaffected by interference from other proteins. The lower limit of
      detection of the assays was equal to the lowest sensor concentration in the
      solution that can be unambiguously detected, typically less than 1 nM. The
      dynamic range of the assays was determined by identifying the sensor
      concentration above which optical interference between QDs affected adversely the
      observed fluorescence emission intensity. The upper limit of this concentration
      was 2.5 MUM for 4 nm QDs. The ZnSe QD-based sensors were stable and preserved
      ~80% of their initial peak emission intensity after two months in refrigerated
      storage. These biosensors have potential applications in rapid sensing of target
      proteins for emergency and point-of-care diagnostic applications.

PMID- 22960009
TI  - Spectroscopic and atomic force microscopy characterization of the electrografting
      of 3,5-bis(4-diazophenoxy)benzoic acid on gold surfaces.
AB  - The synthesis of a bipodal diazonium salt, 3,5-bis(4-diazophenoxy)benzoic acid,
      and the study of its electrochemical deposition on gold surfaces is presented.
      The presence of the organic layer on the gold surface was characterized using
      atomic force microscopy and X-ray photoelectron spectroscopy, demonstrating the
      presence of phenyl groups, indicative of the grafted layer as well as the
      formation of multilayers, dependent on the electrografting conditions.

PMID- 22960010
TI  - Automated processing integrated with a microflow cytometer for pathogen detection
      in clinical matrices.
AB  - A spinning magnetic trap (MagTrap) for automated sample processing was integrated
      with a microflow cytometer capable of simultaneously detecting multiple targets
      to provide an automated sample-to-answer diagnosis in 40 min. After target
      capture on fluorescently coded magnetic microspheres, the magnetic trap
      automatically concentrated the fluorescently coded microspheres, separated the
      captured target from the sample matrix, and exposed the bound target sequentially
      to biotinylated tracer molecules and streptavidin-labeled phycoerythrin. The
      concentrated microspheres were then hydrodynamically focused in a microflow
      cytometer capable of 4-color analysis (two wavelengths for microsphere
      identification, one for light scatter to discriminate single microspheres and one
      for phycoerythrin bound to the target). A three-fold decrease in sample
      preparation time and an improved detection limit, independent of target
      preconcentration, was demonstrated for detection of Escherichia coli 0157:H7
      using the MagTrap as compared to manual processing. Simultaneous analysis of
      positive and negative controls, along with the assay reagents specific for the
      target, was used to obtain dose-response curves, demonstrating the potential for
      quantification of pathogen load in buffer and serum.

PMID- 22960011
TI  - An electrochemiluminescent DNA sensor based on nano-gold enhancement and
      ferrocene quenching.
AB  - An electrochemiluminescent DNA (ECL-DNA) sensor based on nano-gold signal
      enhancement (i.e. gold nanoparticles, GNP) and ferrocene signal quenching was
      investigated. The Au electrode was first modified with GNPs through
      electrodeposition method, followed by subsequent immobilization of single
      stranded probe DNA labeled with ruthenium complex. The resulting sensor produced
      a higher ECL signal due to its higher density of self-assembled probe DNAs on the
      surface. Upon the hybridization of probe DNA with complementary target DNA
      labeled with ferrocene, ECL intensity decreased significantly due to spatial
      separation of ECL label from the electrode surface. As a result, the ECL signal
      was simultaneously quenched by ferrocene. The effects of both nano-gold
      electrodeposition time and ferrocene on the performance of ECL-DNA sensor were
      studied in detail and possible reasons for these effects were suggested as well.
      The reported ECL-DNA sensor showed great sensitivity and may provide an
      alternative approach for DNA detection in diagnostics and gene analysis.

PMID- 22960012
TI  - Nanoaggregates of micropurified lipopolysaccharide identified using dynamic light
      scattering, zeta potential measurement, and TLR4 signaling activity.
AB  - Nanoaggregates composed of selected glycoforms from Escherichia coli 055:B5
      lipopolysaccharide (LPS) were prepared by combining sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis, zinc-imidazole reverse staining, zinc
      chelation after cutting gel slices, elution with either 0.5% triethylamine (TEA)
      or 0.4% to 0.5% surfactant (SDS or deoxycholate [DOC]) from extrusion-generated
      gel microparticles, and centrifugal diafiltration after appropriate surfactant
      dilution. Dynamic light scattering allows detecting these aggregates, giving a
      size distribution from 10 to 100nm in diameter. The formation of the aggregates
      prepared with selected DOC-eluted LPS glycoforms was notably improved over those
      prepared with TEA-eluted glycoforms. As the O-side chain length increased in the
      composition of the former aggregates, there was a gradual decrease in the
      electrophoretic mobility (from -1.2 to 0.0110(-8)m(2)/Vs), giving a calculated
      zeta potential from -15 to 0.1mV at pH6.8. These aggregates were further
      characterized for their abilities to elicit agonistic effects on human Toll-like
      receptor 4, as shown by in vitro activation of nuclear factor kappa light chain
      enhancer of activated B cells (NF-kappaB) in engineered HEK293 cells.

PMID- 22960013
TI  - A NanoDrop-based method for rapid determination of viability decline in
      suspension cultures of animal cells.
AB  - We describe a rapid method for monitoring the cell growth and decline phases in
      suspension cultures of animal cells. During the cell growth phase, ultraviolet
      (UV)-absorbing components in the medium are consumed, but at later times as cells
      begin to die, UV-absorbing molecules such as proteins are released into the
      medium. Measuring the absorbance at 280nm (A(280)) with a NanoDrop
      spectrophotometer, an inverse correlation between the onset of the cell decline
      phase and A(280) was observed. This simple method can be applied to quickly
      determine the beginning of the decline phase of cultures of mammalian and insect
      cells in suspension.

PMID- 22960014
TI  - Development of a sensitive enzyme-linked immunosorbent assay for the detection of
      fumonisin B1 in maize.
AB  - Fumonisin B1 (FB1) is a mycotoxin, mainly produced by Fusarium fungi and present
      in food and feed. It causes harmful effects on human and animal health.
      Therefore, it is necessary to develop sensitive and reliable screening methods.
      In this study, a highly sensitive monoclonal antibody (MAb) against FB1, clone
      2D7, was produced, and the 50% inhibition concentration (IC50) of the MAb was 2.2
      ng/mL in buffer. The MAb showed high cross-reactivity with fumonisin B2 (FB2),
      and negligible cross-reactivity with other mycotoxins. A sensitive indirect
      competitive enzyme-linked immunosorbent assay (icELISA) based on this MAb was
      developed for the determination of FB1 in maize. In spiked samples (100, 200 and
      500 MUg/kg), the average recoveries ranged from 78 +/- 11 to 107 +/- 4%, and the
      coefficient of variation ranged from 3 to 15%. The limit of detection of the
      icELISA was 5.4 MUg/kg. This method was compared to liquid chromatography tandem
      mass spectrometry (LC-MS/MS) using naturally contaminated samples, and the
      correlation coefficient was above 0.82. These results show the reliability of the
      icELISA method for the determination of FB1 in maize.

PMID- 22960015
TI  - The region-specific activation of Ca2+/calmodulin dependent protein kinase II and
      extracellular signal-regulated kinases in hippocampus following chronic alcohol
      exposure.
AB  - Previous studies suggest that hippocampal CA1, CA3, and DG regions may have
      distinct roles in alcohol dependence. Extracellular signal-regulated kinases
      (ERKs) and Ca(2+)/calmodulin dependent protein kinase II (CaMKII) have been shown
      to contribute to the molecular mechanism underlying drug dependence and relapse,
      and there may be an interaction between the activation of ERKs and CaMKII.
      However, little is known regarding the mechanisms underlying the effects of
      alcohol exposure, withdrawal, and relapse, particularly with regard to the
      interaction between CaMKII and ERK1/2 signaling in hippocampal subregions. In the
      present study, rats were provided water containing 6% alcohol as their only
      drinking source. We found that alcohol exerted locomotor stimulant and anxiolytic
      effects on rats in open field behaviors. Following chronic alcohol exposure,
      phospho-ERK1/2 was significantly decreased in the DG. Alcohol withdrawal was
      associated with an increase of phospho-ERK1/2 in the CA1 and DG, while alcohol re
      exposure induced a decrease of phospho-ERK1/2 in the CA1, CA3, and DG. The
      activation of CaMKII (Thr286) correlated with the effects of alcohol on phospho
      ERK1/2. Our results indicate that region-specific activation CaMKII-ERK1/2
      signaling in the hippocampal CA1 and DG may play an important role in alcohol
      dependence.

PMID- 22960016
TI  - A horizontally transferred cyanase gene in the spider mite Tetranychus urticae is
      involved in cyanate metabolism and is differentially expressed upon host plant
      change.
AB  - The genome of the phytophagous two-spotted spider mite Tetranychus urticae was
      recently sequenced, representing the first complete chelicerate genome, but also
      the first genome of a highly polyphagous agricultural pest. Genome analysis
      revealed the presence of an unexpected high number of cases of putative
      horizontal gene transfers, including a gene that encodes a cyanase or cyanate
      lyase. In this study we show by recombinant expression that the T. urticae
      cyanase remained functionally active after horizontal gene transfer and has a
      high affinity for cyanate. Cyanases were also detected in other plant parasitic
      spider mites species such as Tetranychus evansi and Panonychus citri, suggesting
      that an ancient gene transfer occurred before the diversification within the
      Tetranychidae family. To investigate the potential role of cyanase in the
      evolution of plant parasitic spider mites, we studied cyanase expression patterns
      in T. urticae in relation to host plant range and cyanogenesis, a common plant
      defense mechanism. Spider mites can alter cyanase expression levels after
      transfer to several new host plants, including the cyanogenic Phaseolus lunatus.
      However, the role of cyanase is probably not restricted to cyanide response, but
      likely to the plant nutritional quality as a whole. We finally discuss potential
      interactions between cyanase activity and pyrimidine and amino acid synthesis.

PMID- 22960017
TI  - Optimal policies aimed at stabilization of populations with logistic growth under
      human intervention.
AB  - This work examines both positive and negative impacts that economic growth may
      have on the ecological dynamics and stability of a single biological species.
      Local extinction of the species may force the social planner to implement
      defensive expenditures aimed at conservation of the species population by means
      of habitat protection. The latter may lead to an ecological equilibrium that will
      be different from the natural equilibrium that would have arisen in the absence
      of human intervention. Moreover, the existence of such equilibrium is formally
      demonstrated and its stability properties are revised. Additionally, optimal
      choice decision policies are constructed on the basis of Pontryagin's maximum
      principle. Under such policies together with initial abundance of the species,
      the growth trajectories will move the system towards the fixed point of maximum
      species abundance.

PMID- 22960018
TI  - Investigation of the vitamin D receptor gene (VDR) and its interaction with
      protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet
      autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young
      (DAISY).
AB  - The present study investigated the association between variants in the vitamin D
      receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene
      (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet
      autoimmunity (IA) and progression to type 1 diabetes (T1D). The Diabetes
      Autoimmunity Study in the Young (DAISY) has followed children at increased risk
      of T1D since 1993. Of the 1692 DAISY children genotyped for VDR rs1544410, VDR
      rs2228570, VDR rs11568820, PTPN2 rs1893217, and PTPN2 rs478582, 111 developed IA,
      defined as positivity for GAD, insulin or IA-2 autoantibodies on 2 or more
      consecutive visits, and 38 IA positive children progressed to T1D. Proportional
      hazards regression analyses were conducted. There was no association between IA
      development and any of the gene variants, nor was there evidence of a VDR*PTPN2
      interaction. Progression to T1D in IA positive children was associated with the
      VDR rs2228570 GG genotype (HR: 0.49, 95% CI: 0.26-0.92) and there was an
      interaction between VDR rs1544410 and PTPN2 rs1893217 (p(interaction)=0.02). In
      children with the PTPN2 rs1893217 AA genotype, the VDR rs1544410 AA/AG genotype
      was associated with a decreased risk of T1D (HR: 0.24, 95% CI: 0.11-0.53,
      p=0.0004), while in children with the PTPN2 rs1893217 GG/GA genotype, the VDR
      rs1544410 AA/AG genotype was not associated with T1D (HR: 1.32, 95% CI: 0.43
      4.06, p=0.62). These findings should be replicated in larger cohorts for
      confirmation. The interaction between VDR and PTPN2 polymorphisms in the risk of
      progression to T1D offers insight concerning the role of vitamin D in the
      etiology of T1D.

PMID- 22960020
TI  - Thirty-day vein remodeling is predictive of midterm graft patency after lower
      extremity bypass.
AB  - OBJECTIVE: Successful adaptation of a vein graft to an arterial environment is
      incompletely understood. We sought to investigate whether early vein graft
      remodeling is predictive of subsequent patency. METHODS: A prospective
      longitudinal study was conducted of 67 patients undergoing lower extremity bypass
      with autogenous vein between February 2004 and April 2008. Preoperative blood
      samples were drawn for biomarkers. During the bypass operation, a 5-cm index
      segment of the graft was registered for serial lumen diameter measurements at 0,
      1, 3, 6, 9, and 12 months using duplex ultrasound imaging. The imaging substudy
      analysis included patients with at least two ultrasound assessments. RESULTS:
      Patients (55% male) were a median age of 70 years (interquartile range [IQR], 59
      76 years), 40% had diabetes mellitus, 49% had critical limb ischemia, 75% were
      taking a statin, and 91% were taking an antiplatelet medication. Median follow-up
      was 32 months (IQR, 15-47 months). The median baseline high-sensitivity C
      reactive protein level (hsCRP) was 3.2 mg/L (IQR, 1.4-9.7 mg/L). The average
      intraoperative, postimplantation vein lumen diameter was 3.9+/-1.0 mm, increasing
      to 4.7+/-1.1 mm at 1 month, an average 24%+/-27% change per patient. By 3 months,
      the average lumen diameter was 5.1+/-1.6 mm, with little subsequent change
      observed to 12 months. Nonwhite race, baseline hsCRP >=5 mg/L, statin use, and
      initial lumen diameter were significantly associated with early (0- to 1-month)
      vein remodeling in a multivariable regression model. The primary patency rate for
      the cohort was 60%+/-6.3% at 2 years. Initial lumen diameter of the index segment
      was not associated with primary patency, whereas larger lumen diameter achieved
      at 1 month (>=5.1 mm) was positively associated with primary patency (log-rank,
      P=.03). Early (30-day) remodeling behavior was used to divide patients into "poor
      remodelers" (<-5% lumen diameter change, n=6), "modest remodelers" (-5% to 25%
      change, n=29), and "robust remodelers" (>+25% change, n=30). Early remodeling
      category was significantly associated with primary patency rate at 2 years (log
      rank, P=.02). A multivariable Cox proportional hazards model showed that modest
      remodelers (hazard ratio, 3.9; 95% confidence interval, 1.02-15; P=.04) and poor
      remodelers (hazard ratio, 13; 95% confidence interval; P=.008) had significantly
      higher hazard ratios for graft failure than robust early remodelers. CONCLUSIONS:
      Early remodeling of the arterialized vein appears to predict midterm bypass graft
      patency. In addition to baseline diameter, race, inflammation, hsCRP, and statin
      use are associated with early adaptive remodeling, but the mechanisms for these
      observations are not understood.

PMID- 22960021
TI  - A diffusion-weighted magnetic resonance imaging-based study of transcervical
      carotid stenting with flow reversal versus transfemoral filter protection.
AB  - BACKGROUND: Transfemoral carotid artery stenting (CAS) has been associated with a
      high incidence of embolic phenomena and silent brain infarction. The goal of this
      study was to compare the incidence of new ischemic cerebral lesions on diffusion
      perfusion magnetic resonance imaging (MRI) sequences after transcervical CAS
      performed with carotid flow reversal vs stenting via transfemoral approach with
      distal filter protection. METHODS: During a 26-month period, 64 consecutive
      patients diagnosed with significant carotid stenosis by ultrasound imaging were
      assigned to transcervical CAS with carotid flow reversal or a transfemoral
      approach with a distal filter. The Rankin stroke scale was administered by an
      independent neurologist, and diffusion-weighted MRI (DW-MRI) studies were
      performed <=24 hours before and <=24 to 48 hours after the procedure. DW-MRI
      studies were compared by two neuroradiologists not involved in the study and
      blinded for time, clinical status, and treatment option. Hyperintense DW-MRI
      signals found after the procedure were interpreted as postoperative ischemic
      infarcts. All patients were assessed at 1, 6, and 12 months after the
      intervention. RESULTS: The distribution of demographic and pathologic variables
      was similar in both groups. All procedures were technically successful, with a
      mean carotid flow reversal time of 22 minutes. Twenty-one (70%) and 23 patients
      (69.69%) were symptomatic in the transcervical and transfemoral groups,
      respectively (P=.869). After intervention, new postprocedural DW-MRI ischemic
      infarcts were found in four transcervical (12.9%) and in 11 transfemoral (33.3%)
      patients (P=.03), without new neurologic symptoms. No major adverse events
      occurred at 30 days after the intervention. All patients remained neurologically
      intact, without an increase in stroke scale scoring. All stents remained patent,
      and all patients remained stroke-free during follow-up. In multivariate analysis,
      age (relative risk [RR], 1.022; P<.001), symptomatic status (RR, 4.109; P<.001),
      and open-cell vs closed-cell stent design (RR, 2.01; P<.001) were associated with
      a higher risk of embolization in the transfemoral group but not in the
      transcervical group. CONCLUSIONS: These data suggest that transcervical carotid
      stenting with carotid flow reversal carries a significantly lower incidence of
      new ischemic brain infarcts than that resulting from transfemoral CAS with a
      distal filter. The transcervical approach with carotid flow reversal may improve
      the safety of CAS and has the potential to improve results in especially
      vulnerable patients such as the elderly and symptomatic.

PMID- 22960022
TI  - Association of smooth muscle cell phenotypes with extracellular matrix disorders
      in thoracic aortic dissection.
AB  - OBJECTIVE: Extracellular matrix dysregulation in the aortic media has been
      considered as the intrinsic factor for the formation of thoracic aortic
      dissection. However, the mechanisms of extracellular matrix disorders in the
      dissected aortic media remain unclear. This study was designed to investigate the
      relevance between smooth muscle cell phenotypes and extracellular matrix
      disorders in the dissected media. Their interaction may account for the
      pathogenesis of thoracic aortic dissection. METHODS AND RESULTS: Thoracic aortic
      samples were collected from 10 patients with thoracic aortic dissection and 10
      controls. Primary cultures of aortic medial smooth muscle cells were obtained
      with optimized explant technique. In this study, alpha-smooth muscle actin,
      smooth muscle myosin heavy chain 2, and smoothelin were applied as the
      contractile phenotypic markers and osteopontin was applied as the synthetic
      marker. Compared with controls, immunostaining and immunoblotting demonstrated
      that in vivo expression of alpha-smooth muscle actin, smooth muscle myosin heavy
      chain 2, and smoothelin were significantly decreased in the dissected media,
      whereas that of osteopontin was elevated (P<.01 for all). In vitro expression of
      the phenotypic markers showed the similar patterns. Furthermore, smooth muscle
      cells derived from the dissected media exhibited enhanced proliferation (P<.01),
      increased collagens I and III synthesis (2.6- and 4.4-fold, respectively; P<.01
      for both), and elevated matrix metalloproteinase-2 production (4.2-fold; P<.01).
      Consistently, the protein levels of type I and III collagens and matrix
      metalloproteinase-2 in the dissected media were raised by 4.6-, 4.0-, and 3.7
      fold, respectively (P<.01 for all). Collagen deposition was correspondingly
      increased and elastic fibers were decreased and disrupted. CONCLUSIONS: Smooth
      muscle cells in the dissected media exhibit phenotypic switching from the
      contractile to the synthetic type. The synthetic smooth muscle cells increase
      collagen synthesis and matrix metalloproteinase-2 production, both of which can
      promote collagen deposition and elastin degradation in thoracic aortic
      dissection.

PMID- 22960023
TI  - Iliac artery recanalization of chronic occlusions to facilitate endovascular
      aneurysm repair.
AB  - INTRODUCTION: Concurrent iliac occlusion and abdominal aortic aneurysm is rare.
      Traditionally, the endovascular approach to these patients has consisted of
      aortouniiliac devices combined with femoral-femoral bypass. With improved
      facility of endovascular techniques, standard bifurcated endografts represent an
      alternative option in these patients. This study examined outcomes of patients
      undergoing iliac recanalization and traditional bifurcated endovascular aneurysm
      repair in the face of access vessel occlusion. METHODS: Outcomes of patients at
      three academic tertiary referral centers who underwent attempted iliac
      recanalization of chronic iliac occlusions and concurrent endovascular aneurysm
      repair of an infrarenal aortic aneurysm were retrospectively reviewed. Patients
      with acute iliac thrombosis and those with severely stenotic (but patent) iliac
      vessels were excluded. RESULTS: During a 6-year period, 15 occluded iliac
      arteries were treated in 14 patients (13 men). Mean age was 67.8 years (range, 52
      80 years). Primary indication for intervention was disabling claudication in four
      patients, size of abdominal aortic aneurysm in nine, and symptomatic aneurysm in
      one. Seven patients presented with a unilateral common iliac artery (CIA)
      occlusion, four with a unilateral external iliac artery (EIA) occlusion, three
      with a unilateral combined CIA and EIA occlusion, and one with bilateral CIA
      occlusions. Stents had been placed previously in two of the occluded CIAs and in
      one of the occluded EIAs. Average length of the occluded segment was 7.5 cm
      (range, 2-17 cm). The occluded CIAs and EIAs had mean diameters of 8.6 and 5.7
      mm, respectively. Successful recanalization was achieved in 14 of the 15 vessels
      (93.3%). One EIA ruptured during recanalization but was easily controlled with a
      covered stent. A re-entry device was used in two cases. Overall, 13 bifurcated
      devices were successfully implanted. Bilateral iliac occlusions in one patient
      were recanalized. One Talent (Medtronic, Santa Rosa, Calif), eight Excluder (W.
      L. Gore and Associates, Flagstaff, Ariz), and four Zenith (Cook Medical,
      Bloomington, Ind) devices were used. Mean length of stay was 2.3 days (range, 1-6
      days). No major perioperative complications or deaths occurred. During a mean
      follow-up of 28.2 months (range, 1-86 months), there was 100% primary patency of
      successfully recanalized iliac arteries. Aneurysm sac size decreased from a mean
      of 5.1 cm (range, 3.1-7.6 cm) preoperatively to 4.4 cm (range, 2.8-7.1 cm) at
      follow-up. No aneurysms grew or ruptured. Three type II endoleaks occurred, one
      of which required coiling at 15 months. Two late deaths occurred: one at 36
      months secondary to complications from a coronary artery bypass graft/mitral
      valve replacement and one at 34 months from a myocardial infarction. CONCLUSIONS:
      The use of bifurcated endovascular devices after recanalization of an occluded
      iliac system is technically feasible and durable at midterm follow-up. This
      technique re-establishes aortoiliac inflow to both lower extremities, obviates
      the need for extra-anatomic bypass, and may preserve hypogastric perfusion in
      some patients.

PMID- 22960024
TI  - Surgeon-modified fenestrated-branched stent grafts to treat emergently ruptured
      and symptomatic complex aortic aneurysms in high-risk patients.
AB  - INTRODUCTION: Fenestrated-branched stent grafts have been developed as a
      minimally invasive, endovascular alternative for the treatment of complex aortic
      aneurysms in high-risk patients. However, the manufacture of these devices can
      take as long as 6 to 12 weeks, and therefore, they cannot be used to treat aortic
      emergencies. We reviewed our experience with surgeon-modified, fenestrated
      branched stent grafts (sm-FBSGs) in high-risk patients who presented as
      emergencies with ruptured or symptomatic complex aortic aneurysms. METHODS: All
      patients treated with sm-FBSGs at our institution were retrospectively reviewed.
      Patients presenting with acute symptoms or an emergency indication for repair
      were analyzed. RESULTS: Twelve high-risk patients (nine men), of which seven were
      at American Society of Anesthesiologists class 4 and five were at class 3,
      presented with seven symptomatic and five ruptured aortic aneurysms. Mean age was
      71 years (range, 52-86 years), and mean maximal aneurysm size was 8.1 cm (range,
      5-12 cm). Six patients (50%) had prior aortic surgery or a hostile abdomen.
      Relevant comorbidities included coronary disease in all 12 patients, and seven
      (58%) had an ejection fraction<=35%. Nine patients (75%) had severe pulmonary
      dysfunction. Four aneurysms were pararenal, and eight were thoracoabdominal (two
      type II, three type III, and three type IV). An average of three visceral vessels
      (range, 2-4) were treated per patient, with 35 branches targeted. Endografts were
      successfully implanted in all patients. There was no paraplegia or intraoperative
      death. One patient (8.3%) died of subarachnoid hemorrhage<=30 days.
      Reintervention was necessary in two patients, for a type 3 endoleak and for
      evacuation of a retroperitoneal hematoma. Morbidity included one myocardial
      infarction, and two patients each with transient respiratory failure and
      transient renal insufficiency not requiring dialysis. Mean postoperative length
      of stay was 4 days in the intensive care unit and 8 days in the hospital. At a
      mean follow-up of 9 months (range, 3-18 months), two patients died of non
      aneurysm-related causes. Branch vessel patency was 100%. No late reinterventions
      were necessary. No type I or III endoleaks occurred. One type II endoleak is
      under observation. CONCLUSIONS: Sm-FBSG may play an important role in the
      treatment of select patients with symptomatic or ruptured complex aortic
      aneurysms who are at prohibitive risk for open surgery and in whom endovascular
      repair cannot be delayed to allow implantation of a custom-made commercial
      device. Until an off-the-shelf fenestrated-branched device is created that does
      not require a prolonged waiting period, this may be the best option to treat
      patients with symptomatic or ruptured complex aneurysms that are at excessively
      high surgical risk.

PMID- 22960025
TI  - The first cardiac catheter.

PMID- 22960027
TI  - Dehydration-induced shrinkage of dentin as a potential cause of vertical root
      fractures.
AB  - Vertical root fractures (VRF) of endodontically treated teeth constitute a severe
      clinical condition frequently requiring removal of the affected tooth. Numerous
      attempts have been made to find the cause for VRF without reaching definitive
      conclusions. As changes in moisture content have been reported to appear as a
      consequence of root canal therapy, it is the goal of this paper to evaluate
      associated volume changes as a possible cause for VRF. Considering disk shaped
      horizontal cross sections of endodontically treated teeth with a moisture content
      of dentin decreasing from the root surface towards the root canal, both relative
      circumferential and relative radial stresses resulting from volume changes of
      dentin were calculated. It could be shown that the presence of a root canal
      itself increases radial and circumferential stresses acting on root dentin by a
      factor of two. Reduction in moisture content of dentin at the wall of the root
      canal results in shrinkage of the tooth structure and tensile stress. On the
      outer surface of the root, compressive stresses occur. Thus, VRF would start at
      the canal wall and propagate to the root surface. The theory presented appears to
      be consistent with previous reports on stress development as a consequence of
      dehydration of dentin and finite element analysis on root fractures. It may be
      concluded that dehydration of dentin induces cracks at the walls of a root canal
      which subsequently grow as a result of cyclic loading or traumatic overload.

PMID- 22960026
TI  - Epigenetic responses to stress: triple defense?
AB  - Stressful conditions for plants can originate from numerous physical, chemical
      and biological factors, and plants have developed a plethora of survival
      strategies including developmental and morphological adaptations, specific
      signaling and defense pathways as well as innate and acquired immunity. While it
      has become clear in recent years that many stress responses involve epigenetic
      components, we are far from understanding the mechanisms and molecular
      interactions. Extending our knowledge is fundamental, not least for plant
      breeding and conservation biology. This review will highlight recent insights
      into epigenetic stress responses at the level of signaling, chromatin
      modification, and potentially heritable consequences.

PMID- 22960028
TI  - Perilunate dislocations and fracture dislocations.
AB  - Perilunate dislocations and fracture dislocations are high-energy injuries that
      can result in pain, stiffness, weakness, or disability if inappropriately
      treated. Prompt recognition and surgical treatment with anatomic reduction of
      carpal malalignment improve the likelihood of optimal, long-term clinical success
      and patient satisfaction. The progressive development of radiographic evidence of
      arthrosis is common but has not been shown to consistently correlate with worse
      patient function and outcomes.

PMID- 22960029
TI  - Normative data on wrist function.
AB  - PURPOSE: In clinical day-to-day life, grip strength, key pinch, and range of
      motion (ROM) serve to objectively evaluate treatment outcomes on wrist
      interventions. The goals of this study were to generate normative values of wrist
      function including the parameters of grip strength, key pinch, wrist ROM, and
      Disabilities of the Arm, Shoulder, and Hand (DASH) scores in a healthy, working
      population, and to investigate the influence of age, sex, body weight and height,
      handedness, and work strain. METHODS: We clinically examined 750 volunteer
      working subjects (363 women and 387 men, all white). We divided subjects into 2
      groups depending on whether their labor involved high or low manual strain. We
      recorded participants' height, weight, grip strength, pinch strength, and wrist
      ROM. Each participant filled out a DASH questionnaire. RESULTS: Grip strength and
      pinch strength showed a maximum at between 30 and 49 years of age. In men, body
      mass index, body height, and weight all correlated with grip strength and pinch
      grip. Whereas women exhibited greater grip strength on the right side, men showed
      nonsignificant greater grip strength on the left side. Wrist ROM was greatest for
      ages ranging between 18 and 29 years. The average DASH value for all male
      subjects was significantly less than that of female subjects. In a healthy
      working population, the DASH score increased yearly by an average of 0.2 points
      in men and 0.3 points in women. CONCLUSIONS: This study showed that in a healthy
      working population, people 30 to 49 years of age had the highest grip strength
      and pinch strength. Age positively correlated with the DASH score and inversely
      related to wrist ROM. Persons employed in jobs with high manual strain presented
      with lower wrist ROM and higher DASH scores. CLINICAL RELEVANCE: These data help
      to objectively evaluate wrist function and the effectiveness of therapeutic
      interventions.

PMID- 22960030
TI  - Metacarpal synostosis: treatment with a longitudinal osteotomy and bone graft
      substitute interposition.
AB  - PURPOSE: To describe a case series of congenital metacarpal synostosis treated
      with longitudinal osteotomy and bone graft substitute interposition. METHODS: We
      retrospectively reviewed charts of all patients with metacarpal synostosis
      treated with a longitudinal osteotomy and bone graft substitute interposition at
      2 institutions. Radiographic and clinical appearances were analyzed at initial
      diagnosis, intraoperatively, and at last follow-up. RESULTS: A total of 10
      patients (14 hands) met the inclusion criteria. Six patients (8 hands)
      demonstrated ring-little finger metacarpal synostosis and 4 patients (6 hands)
      had a middle-ring finger metacarpal synostosis. The median age at operation was 5
      years (range, 2-16 y). Follow-up ranged from 1 to 14 years (average, 3 y).
      Associated hand anomalies included polydactyly, symbrachydactyly, and
      clinodactyly. Before surgery, the little finger proximal phalanx was angulated
      away from the middle finger metacarpal on average 46 degrees  (range, 26 degrees 
      60 degrees ), and the angulation between the middle and the ring fingers averaged
      43 degrees  (range, 26 degrees -50 degrees ). Postoperative correction at 1 year
      was statistically significant for both ring-little finger metacarpal synostosis,
      average 23 degrees  (range, 10 degrees -30 degrees ), and middle-ring finger
      metacarpal synostosis, average 16 degrees  (range, 5 degrees -44 degrees ).
      Recurrence of digital abduction was evident in 2 patients who had middle-ring
      finger metacarpal synostosis. CONCLUSIONS: Metacarpal synostosis is an uncommon
      congenital hand anomaly characterized by the coalescence of 2 adjacent
      metacarpals. In the most common form, the ring and little finger metacarpals are
      associated with abduction of the small finger in an awkward position. Use of the
      described technique is safe and effective, yet concerns remain regarding mild
      persistent angulation and risk of recurrence. CLINICAL RELEVANCE: Congenital
      metacarpal synostosis may be effectively treated with a longitudinal osteotomy,
      realignment of component metacarpals, and interposition of bone graft substitute.
      When the procedure is performed at a young age, we recommend follow-up until
      skeletal maturity to identify recurrence of the deformity. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 22960031
TI  - Putative roles for a rhamnose binding lectin in Flavobacterium columnare
      pathogenesis in channel catfish Ictalurus punctatus.
AB  - Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare,
      continues to be a major problem worldwide and commonly leads to tremendous losses
      of both wild and cultured freshwater fish, particularly in intensively farmed
      aquaculture species such as channel catfish. Despite its ecologic and economic
      impacts, the fundamental molecular mechanisms of the host immune response to this
      pathogen remain unclear. While F. columnare can induce marked pathologic changes
      in numerous ectopic tissues, the adhesion of F. columnare to the gill in
      particular is strongly associated with pathogen virulence and host
      susceptibility. Recently, in this regard, using RNA-seq expression profiling we
      found that a rhamnose-binding lectin (RBL) was dramatically upregulated in the
      gill of fish infected with F. columnare (as compared to naive fish). Thus, in the
      present study we sought to further characterize and understand the RBL response
      in channel catfish (Ictalurus punctatus). We first identified two distinct
      catfish families with differential susceptibilities to columnaris disease; one
      family was found to be completely resistant while the other was susceptible (0%
      mortality versus 18.3% respectively, P < 0.001). Exclusively, in the susceptible
      family, we observed an acute and robust upregulation in catfish RBL that
      persisted for at least 24 h (P < 0.05). To elucidate whether RBL play a more
      direct role in columnaris pathogenesis, we exposed channel catfish to different
      doses of the putative RBL ligands l-rhamnose and d-galactose, and found that
      these sugars, protected channel catfish against columnaris disease, likely
      through competition with F. columnare binding of host RBL. Finally, we examined
      the role of nutritional status on RBL regulation and found that RBL expression
      was upregulated (>120-fold; P < 0.05) in fish fasted for 7 d (as compared to fish
      fed to satiation daily), yet expression levels returned to those of satiated fish
      within 4 h after re-feeding. Collectively, these findings highlight putative
      roles for RBL in the context of columnaris disease and reveal new aspects linking
      RBL regulation to feed availability.

PMID- 22960032
TI  - Manipulating molecular switches in brown adipocytes and their precursors: a
      therapeutic potential.
AB  - Brown adipocytes constitute a metabolically active tissue responsible for non
      shivering thermogenesis and the depletion of excess calories. Differentiation of
      brown fat adipocytes de novo or stimulation of pre-existing brown adipocytes
      within white adipose depots could provide a novel method for reducing the obesity
      and alleviating the consequences of type II diabetes worldwide. In this review,
      we addressed several molecular mechanisms involved in the control of brown fat
      activity, namely, the beta3-adrenergic stimulation of thermogenesis during
      exposure to cold or by catecholamines; the augmentation of thyroid function; the
      modulation of peroxisome proliferator-activated receptor gamma (PPARgamma),
      transcription factors of the C/EBP family, and the PPARgamma co-activator PRDM16;
      the COX-2-driven expression of UCP1; the stimulation of the vanilloid subfamily
      receptor TRPV1 by capsaicin and monoacylglycerols; the effects of BMP7 or its
      analogs; the cannabinoid receptor antagonists and melanogenesis modulating
      agents. Manipulating one or more of these pathways may provide a solution to the
      problem of harnessing brown fat's thermogenic potential. However, a better
      understanding of their interplay and other homeostatic mechanisms is required for
      the development of novel therapies for millions of obese and/or diabetic
      individuals.

PMID- 22960033
TI  - What is a food and what is a medicinal product in the European Union? Use of the
      benchmark dose (BMD) methodology to define a threshold for "pharmacological
      action".
AB  - The decision criterion for the demarcation between foods and medicinal products
      in the EU is the significant "pharmacological action". Based on six examples of
      substances with ambivalent status, the benchmark dose (BMD) method is evaluated
      to provide a threshold for pharmacological action. Using significant dose
      response models from literature clinical trial data or epidemiology, the BMD
      values were 63mg/day for caffeine, 5g/day for alcohol, 6mg/day for lovastatin,
      769mg/day for glucosamine sulfate, 151mg/day for Ginkgo biloba extract, and
      0.4mg/day for melatonin. The examples for caffeine and alcohol validate the
      approach because intake above BMD clearly exhibits pharmacological action.
      Nevertheless, due to uncertainties in dose-response modelling as well as the need
      for additional uncertainty factors to consider differences in sensitivity within
      the human population, a "borderline range" on the dose-response curve remains.
      "Pharmacological action" has proven to be not very well suited as binary decision
      criterion between foods and medicinal product. The European legislator should
      rethink the definition of medicinal products, as the current situation based on
      complicated case-by-case decisions on pharmacological action leads to an
      unregulated market flooded with potentially illegal food supplements.

PMID- 22960034
TI  - The role of long non-coding RNA in transcriptional gene silencing.
AB  - Transcriptional gene silencing controls the activity of transposable elements and
      expression of protein-coding genes. It requires non-coding transcription, which
      in plants is performed by RNA Polymerases IV and V (Pol IV and Pol V). Pol IV
      produces precursors for siRNA biogenesis while Pol V produces scaffold
      transcripts required for siRNAs and associated proteins to recognize their target
      loci. In this review I discuss the mechanisms used by Pol IV and Pol V to mediate
      repressive chromatin modifications. I further discuss the mechanisms controlling
      non-coding transcription and their role in regulation of genome activity.

PMID- 22960036
TI  - Influence of biofouling on pharmaceuticals rejection in NF membrane filtration.
AB  - The effects of biomass attachment and growth on the surface characteristics and
      organic micropollutants rejection performance of nanofiltration membranes were
      investigated in a pilot installation. Biomass growth was induced by dosing of a
      readily biodegradable carbon source resulting in the formation of a biofouling in
      the investigated membrane elements. Surface properties and rejection behaviour of
      a biofouled and virgin membrane were investigated and compared in terms of
      surface charge, surface energy and hydrophobicity. The last two were accomplished
      by performing contact angle measurements on fully hydrated membrane surfaces, in
      order to mimic the operating conditions of a membrane in contact with water.
      Compared to a virgin membrane, deposition and growth of biofilm did slightly
      alter the surface charge, which became more negative, and resulted in a higher
      hydrophilicity of the membrane surface. In addition, the presence of the
      negatively charged biofilm induced accumulation of positively charged
      pharmaceuticals within the biomass layer, which probably also hindered back
      diffusion. This caused a reduction in rejection efficiency of positively charged
      solutes but did not alter rejection of neutral and negatively charged
      pharmaceuticals. Pharmaceuticals rejection was found to positively correlate with
      the specific free energy of interaction between virgin or biofouled membranes and
      pharmaceuticals dissolved in the water phase. The rejection values obtained with
      both virgin and biofouled membranes were compared and found in good agreement
      with the predictions calculated with a solute transport model earlier developed
      for high pressure filtration processes.

PMID- 22960035
TI  - Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on
      Ras.
AB  - We report the novel finding that Phospholipase D2 (PLD2), through its PX and PH
      domains, binds specifically to Ras and catalyzes the GDP/GTP exchange (i.e., is a
      GEF), with potency comparable to Ras-GRF-1, a known Ras-GEF. Cells overexpressing
      PLD2-GEF inactive mutants (F129Y and R172C/L173A) fail to stimulate cell
      proliferation compared to the wild type-expressing cells. The GEF effect on Ras
      follows a faster kinetics than other GTPase substrates (such as Rac2 or Rac1) and
      is a better substrate, too. The GEF action is due to PLD2 (protein) itself,
      independent of the lipase product PA. PA can still have a fine-tuning regulatory
      effect on Ras-GTP depending upon its cellular concentration. Rapidly growing
      human breast cancer cells MDA-MB 231 (but not the slow growing MCF7 counterpart)
      have high levels of endogenous PLD2-GEF which correlates with high Ras
      activation. The PLD2-"GEF" activity is even higher than the classical "lipase"
      activity and is abrogated with GEF single point mutants, particularly F129Y, and
      concomitantly with a slow rate of cell growth. This can be crucial to cancer
      biology in that not only Ras mutations explain abnormal growth, but the existence
      of a new GEF for Ras: a GEF molecule that happens to be a phospholipase.

PMID- 22960037
TI  - Continuous bioscorodite crystallization in CSTRs for arsenic removal and
      disposal.
AB  - In CSTRs, ferrous iron was biologically oxidized followed by crystallization of
      scorodite (FeAsO(4).2H(2)O) at pH 1.2 and 72  degrees C. The CSTRs were fed with
      2.8 g L(-1) arsenate and 2.4 g L(-1) ferrous and operated at an HRT of 40 h,
      without seed addition or crystal recirculation. Both oxidation and
      crystallization were stable for periods up to 200 days. The arsenic removal
      efficiency was higher than 99% at feed Fe/As molar ratios between 1 and 2,
      resulting in effluents with 29 +/- 18 mg As L(-1). Arsenic removal decreased to
      40% at feed Fe/As molar ratios between 2 and 5. Microorganisms were not affected
      by arsenic concentrations up to 2.8 g As(5+) L(-1). The bioscorodite solid yield
      was 3.2 g/g arsenic removed. Bioscorodite crystals precipitated as aggregates,
      causing scaling on the glass wall of the reactor. The observed morphology through
      SE microscopy of the precipitates appeared amorphous but XRD analysis confirmed
      that these were crystalline scorodite. Arsenic leaching of bioscorodite was 0.4
      mg L(-1) after 100 days under TCLP conditions, but when jarosite had been co
      precipitated leaching was higher at 0.8 g L(-1). The robustness of the continuous
      process, the high removal efficiency and the very low arsenic leaching rates from
      bioscorodite sludge make the process very suitable for arsenic removal and
      disposal.

PMID- 22960038
TI  - Teleost growth factor independence (gfi) genes differentially regulate successive
      waves of hematopoiesis.
AB  - Growth Factor Independence (Gfi) transcription factors play essential roles in
      hematopoiesis, differentially activating and repressing transcriptional programs
      required for hematopoietic stem/progenitor cell (HSPC) development and lineage
      specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC),
      myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC,
      megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for
      primitive hematopoiesis; however, little is known about the role of gfi1aa in
      definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we
      report the isolation and characterization of an additional hematopoietic gfi
      factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and
      definitive sites of hematopoiesis in zebrafish. Our functional analyses
      demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and
      definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences
      markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b
      silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for
      definitive hematopoiesis. We determine the epistatic relationships between the
      gfi factors and key hematopoietic transcription factors, demonstrating that
      gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of
      teleost HSPC. Our studies establish a comparative paradigm for the regulation of
      hematopoietic lineages by gfi transcription factors.

PMID- 22960040
TI  - Aurein 2.3 functionality is supported by oblique orientated alpha-helical
      formation.
AB  - In this study, an amphibian antimicrobial peptide, aurein 2.3, was predicted to
      use oblique orientated alpha-helix formation in its mechanism of membrane
      destabilisation. Molecular dynamic (MD) simulations and circular dichroism (CD)
      experimental data suggested that aurein 2.3 exists in solution as unstructured
      monomers and folds to form predominantly alpha-helical structures in the presence
      of a dimyristoylphosphatidylcholine membrane. MD showed that the peptide was
      highly surface active, which supported monolayer data where the peptide induced
      surface pressure changes>34 mNm(-1). In the presence of a lipid membrane MD
      simulations suggested that under hydrophobic mismatch the peptide is seen to
      insert via oblique orientation with a phenylalanine residue (PHE3) playing a key
      role in the membrane interaction. There is evidence of snorkelling leucine
      residues leading to further membrane disruption and supporting the high level of
      lysis observed using calcein release assays (76%). Simulations performed at
      higher peptide/lipid ratio show peptide cooperativity is key to increased
      efficiency leading to pore-formation.

PMID- 22960039
TI  - The dREAM/Myb-MuvB complex and Grim are key regulators of the programmed death of
      neural precursor cells at the Drosophila posterior wing margin.
AB  - Successful development of a multicellular organism depends on the finely tuned
      orchestration of cell proliferation, differentiation and apoptosis from
      embryogenesis through adulthood. The MYB-gene family encodes sequence-specific
      DNA-binding transcription factors that have been implicated in the regulation of
      both normal and neoplastic growth. The Drosophila Myb protein, DMyb (and
      vertebrate B-Myb protein), has been shown to be part of the dREAM/MMB complex, a
      large multi-subunit complex, which in addition to four Myb-interacting proteins
      including Mip130, contains repressive E2F and pRB proteins. This complex has been
      implicated in the regulation of DNA replication within the context of chorion
      gene amplification and transcriptional regulation of a wide array of genes.
      Detailed phenotypic analysis of mutations in the Drosophila myb gene, Dm myb, has
      revealed a previously undiscovered function for the dREAM/MMB complex in
      regulating programmed cell death (PCD). In cooperation with the pro-apoptotic
      protein Grim and dREAM/MMB, DMyb promotes the PCD of specified sensory organ
      precursor daughter cells in at least two different settings in the peripheral
      nervous system: the pIIIb precursor of the neuron and sheath cells in the
      posterior wing margin and the glial cell in the thoracic microchaete lineage.
      Unlike previously analyzed settings, in which the main role of DMyb has been to
      antagonize the activities of other dREAM/MMB complex members, it appears to be
      the critical effector in promoting PCD. The finding that Dm myb and grim are both
      involved in regulating PCD in two distinct settings suggests that these two genes
      may often work together to mediate PCD.

PMID- 22960041
TI  - Conformational dynamics and membrane interactions of the E. coli outer membrane
      protein FecA: a molecular dynamics simulation study.
AB  - The TonB-dependent transporters mediate high-affinity binding and active
      transport of a variety of substrates across the outer membrane of Escherichia
      coli. The substrates transported by these proteins are large, scarce nutrients
      that are unable to gain entry into the cell by passive diffusion across the
      complex, asymmetric bilayer that constitutes the outer membrane. Experimental
      studies have identified loop regions that are essential for the correct
      functioning of these proteins. A number of these loops have been implicated in
      ligand binding. We report the first simulations of an E. coli outer membrane
      protein in an asymmetric model membrane that incorporates lipopolysaccharide
      (LPS) molecules. Comparative simulations of the apo and holo forms of the TonB
      dependent transporter FecA in different membrane models enable us to identify the
      nature of the LPS-protein interactions and determine how these interactions
      impact upon the conformational dynamics of this protein. In particular, our
      simulations provide molecular-level insights into the influence of the
      environment and ligand on the dynamics of the functionally important loops of
      FecA. In addition, we provide insights into the nature of the protein-ligand
      interactions and ligand induced conformational change in FecA.

PMID- 22960042
TI  - Chemical and physical requirements for lipid extraction by bovine binder of sperm
      BSP1.
AB  - The bovine seminal plasma contains phosphocholine-binding proteins, which
      associate to sperm membranes upon ejaculation. These binder-of-sperm (BSP)
      proteins then induce a phospholipid and cholesterol efflux from these membranes.
      In this work, we determined physical and chemical parameters controlling this
      efflux by characterizing the lipid extraction induced by BSP1, the most abundant
      of BSP protein in bull seminal plasma, from model membranes with different
      composition. The model membranes were formed from binary mixtures of 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine (POPC) with 1-palmitoyl-2-hydroxy-sn-glycero
      3-phosphocholine (Lyso-PC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphoserine (POPS) or cholesterol. The modulation of BSP1-induced
      lipid extraction from membranes by their chemical composition and their physical
      properties brings us to propose a 3-step extraction mechanism. First, the protein
      associates with membranes via specific binding to phosphocholine groups. Second,
      BSP1 penetrates in the membrane, essentially in the external lipid leaflet.
      Third, BSP1 molecules solubilize a lipid patch coming essentially from the outer
      lipid leaflet, without any lipid specificity, to ultimately form small
      lipid/protein auto-assemblies. The stoichiometry of these complexes corresponds
      to 10-15 lipids per protein. It is also shown that fluid-phase membranes are more
      prone to BSP1-induced lipid extraction than gel-phase ones. The inhibition of the
      lipid extraction in this case appears to be related to the inhibition of the
      protein penetration in the membrane (step 2) and not to the protein association
      with PC head groups (step 1). These findings contribute to our understanding of
      the mechanism by which BSP1 modify the lipid composition of sperm membranes, a
      key event in sperm capacitation.

PMID- 22960043
TI  - Alemtuzumab induction in renal transplantation: a meta-analysis and systemic
      review.
AB  - OBJECTIVE: To compare the efficacy and safety of alemtuzumab versus traditional
      antibodies for induction therapy in renal transplantation. METHODS: Literature
      searches for all randomized controlled trials comparing alemtuzumab with
      traditional antibodies for post renal transplant induction therapy were performed
      using MEDLINE, EMBASE and the Cochrane Library. Quality assessment was performed
      in each trial. Meta-analyses were performed to demonstrate the pooled effects of
      relative risk (RR) with 95% confidence intervals (CI). RESULTS: A total of 808
      participants from six randomized controlled trials (RCTs) were included.
      Alemtuzumab was associated with lower incidence of biopsy-proven acute rejection
      over traditional antibodies (RR 0.63, CI 0.45-0.87, p=0.005). This difference
      remained when only studies comparing alemtuzumab with rabbit antithymocyte
      globulin were included (RR 0.32, CI 0.11-0.91, p=0.03), but lost significance
      when only patients at high-risk were included (RR 0.86, CI 0.48-1.55, p=0.62). No
      significant differences were detected between alemtuzumab and traditional
      antibodies in terms of delayed graft function, patient death, graft loss, and
      safety profile. CONCLUSIONS: Alemtuzumab induction is superior to traditional
      antibodies in preventing AR in renal transplantation, but this benefit may not
      extend to recipients at high immunologic risk. The lower rejection rates do not
      translate into a uniform increase in graft or patient survival.

PMID- 22960044
TI  - Effect of fasting versus feeding on the bone metabolic response to running.
AB  - Individuals often perform exercise in the fasted state, but the effects on bone
      metabolism are not currently known. We compared the effect of an overnight fast
      with feeding a mixed meal on the bone metabolic response to treadmill running.
      Ten, physically-active males aged 28 +/- 4y (mean +/-SD) completed two,
      counterbalanced, 8d trials. After 3d on a standardised diet, participants
      performed 60 min of treadmill running at 65% VO(2max) on Day 4 following an
      overnight fast (FAST) or a standardised breakfast (FED). Blood samples were
      collected at baseline, before and during exercise, for 3h after exercise, and on
      four consecutive follow-up days (FU1-FU4). Plasma/serum were analysed for the c
      terminal telopeptide region of collagen type 1 (beta-CTX), n-terminal propeptides
      of procollagen type 1 (P1NP), osteocalcin (OC), bone alkaline phosphatase (bone
      ALP), parathyroid hormone (PTH), albumin-adjusted calcium, phosphate,
      osteoprotegerin (OPG), cortisol, leptin and ghrelin. Only the beta-CTX response
      was significantly affected by feeding. Pre-exercise concentrations decreased more
      in FED compared with FAST (47% vs 26%, P<0.001) but increased during exercise in
      both groups and were not significantly different from baseline at 1h post
      exercise. At 3h post-exercise, concentrations were decreased (33%, P<0.001) from
      baseline in FAST and significantly lower (P<0.001) than in FED. P1NP and PTH
      increased, and OC decreased during exercise. Bone markers were not significantly
      different from baseline on FU1-FU4. Fasting had only a minor effect on the bone
      metabolic response to subsequent acute, endurance exercise, reducing the duration
      of the increase in beta-CTX during early recovery, but having no effect on
      changes in bone formation markers. The reduced duration of the beta-CTX response
      with fasting was not fully explained by changes in PTH, OPG, leptin or ghrelin.

PMID- 22960046
TI  - Effects of neuropeptide S on seizures and oxidative damage induced by
      pentylenetetrazole in mice.
AB  - Neuropeptide S (NPS) and its receptor were recently discovered in the central
      nervous system. In rodents, NPS promotes hyperlocomotion, wakefulness,
      anxiolysis, anorexia, and analgesia and enhances memory when injected
      intracerebroventricularly (i.c.v.). Herein, NPS at different doses (0.01, 0.1 and
      1nmol) was i.c.v. administered in mice challenged with pentylenetetrazole (PTZ;
      60mg/kg) repeatedly injected. Aiming to assess behavioral alterations and
      oxidative damage to macromolecules in the brain, NPS was injected 5min prior to
      the last dose of PTZ. The administration of NPS only at 1nmol increased the
      duration of seizures evoked by PTZ, without modifying frequency and latency of
      seizures. Biochemical analysis revealed that NPS attenuated PTZ-induced oxidative
      damage to proteins and lipids in the hippocampus and cerebral cortex. In
      contrast, the administration of NPS to PTZ-treated mice increased DNA damage in
      the hippocampus, but not cerebral cortex. In conclusion, this is the first
      evidence of the potential proconvulsive effects of NPS in mice. The protective
      effects of NPS against lipid and protein oxidative damage in the mouse
      hippocampus and cerebral cortex evoked by PTZ-induced seizures are quite
      unexpected. The present findings were discussed analyzing the paradoxical effects
      of NPS: facilitation of convulsive behavior and protection against oxidative
      damage to lipids and proteins.

PMID- 22960045
TI  - The prenyl-binding protein PrBP/delta: a chaperone participating in intracellular
      trafficking.
AB  - Expressed ubiquitously, PrBP/delta functions as chaperone/co-factor in the
      transport of a subset of prenylated proteins. PrBP/delta features an
      immunoglobulin-like beta-sandwich fold for lipid binding, and interacts with
      diverse partners. PrBP/delta binds both C-terminal C15 and C20 prenyl side chains
      of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras
      superfamily. PrBP/delta also interacts with the small GTPases, ARL2 and ARL3,
      which act as release factors (GDFs) for prenylated cargo. Targeted deletion of
      the mouse Pde6d gene encoding PrBP/delta resulted in impeded trafficking to the
      outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and
      geranylgeranylated, respectively. Rod and cone transducin trafficking was largely
      unaffected. These trafficking defects produce progressive cone-rod dystrophy in
      the Pde6d(-/-) mouse.

PMID- 22960047
TI  - Change in plasma visfatin level after severe traumatic brain injury.
AB  - Higher plasma visfatin concentration has been associated with ischemic stroke.
      Thus, we sought to investigate change in plasma visfatin level after traumatic
      brain injury and to evaluate its relation with disease outcome. Seventy-six
      healthy controls and 98 patients with acute severe traumatic brain injury were
      recruited. Twenty-seven patients (27.6%) died and 48 patients (49.0%) suffered
      from unfavorable outcome (Glasgow outcome scale score of 1-3) in 6 months. On
      admission, plasma visfatin level was increased in patients than in healthy
      controls and was highly correlated with Glasgow Coma Scale score. A multivariate
      analysis identified plasma visfatin level as an independent predictor for 6-month
      mortality and unfavorable outcome. According to receiver operating characteristic
      curve analysis, the predictive value of the plasma visfatin concentration was
      similar to Glasgow Coma Scale score's. In a combined logistic-regression model,
      visfatin did not improve the predictive value of Glasgow Coma Scale score. Thus,
      increased plasma visfatin level is associated with 6-month clinical outcomes
      after severe traumatic brain injury.

PMID- 22960048
TI  - Intravenous phage display identifies peptide sequences that target the burn
      injured intestine.
AB  - The injured intestine is responsible for significant morbidity and mortality
      after severe trauma and burn; however, targeting the intestine with therapeutics
      aimed at decreasing injury has proven difficult. We hypothesized that we could
      use intravenous phage display technology to identify peptide sequences that
      target the injured intestinal mucosa in a murine model, and then confirm the
      cross-reactivity of this peptide sequence with ex vivo human gut. Four hours
      following 30% TBSA burn we performed an in vivo, intravenous systemic
      administration of phage library containing 10(12) phage in balb/c mice to biopan
      for gut-targeting peptides. In vivo assessment of the candidate peptide sequences
      identified after 4 rounds of internalization was performed by injecting 1*10(12)
      copies of each selected phage clone into sham or burned animals. Internalization
      into the gut was assessed using quantitative polymerase chain reaction. We then
      incubated this gut-targeting peptide sequence with human intestine and visualized
      fluorescence using confocal microscopy. We identified 3 gut-targeting peptide
      sequences which caused collapse of the phage library (4-1: SGHQLLLNKMP, 4-5:
      ILANDLTAPGPR, 4-11: SFKPSGLPAQSL). Sequence 4-5 was internalized into the
      intestinal mucosa of burned animals 9.3-fold higher than sham animals injected
      with the same sequence (2.9*10(5)vs. 3.1*10(4) particles per mg tissue).
      Sequences 4-1 and 4-11 were both internalized into the gut, but did not
      demonstrate specificity for the injured mucosa. Phage sequence 4-11 demonstrated
      cross-reactivity with human intestine. In the future, this gut-targeting peptide
      sequence could serve as a platform for the delivery of biotherapeutics.

PMID- 22960049
TI  - Further validation of multiple sclerosis walking scale-12 scores based on
      spatiotemporal gait parameters.
AB  - OBJECTIVE: To examine the association between Multiple Sclerosis Walking Scale-12
      (MSWS-12) scores and spatiotemporal parameters of gait as indicators of gait
      quality among ambulatory persons with multiple sclerosis (MS). DESIGN: Cross
      sectional study. SETTING: University research laboratory. PARTICIPANTS: Community
      residing persons with MS (N=268). INTERVENTION: Not applicable. MAIN OUTCOME
      MEASURES: Main outcome measures included the MSWS-12 and spatial and temporal
      gait parameters (walking speed, cadence, step length, step time, base of support
      [ie, the distance between 1 footfall and the line of progression of the opposing
      foot], and percentage of gait cycle spent in double support). Secondary outcomes
      included the timed 25-foot walk (T25FW), 6-minute walk (6MW), and Patient
      Determined Disease Steps scale. RESULTS: MSWS-12 scores were significantly
      correlated with walking speed (r=-.59), cadence (r=-.50), step length (r=-.53),
      step time (r=.46), base of support (r=.29), and percentage of the gait cycle
      spent in double support (r=.54). MSWS-12 scores further were significantly
      correlated with T25FW (r=.57) and 6MW (r=-.75) scores. CONCLUSIONS: Such findings
      suggest that the MSWS-12 captures aspects of walking quality, assessed as
      spatiotemporal parameters of gait, in addition to walking speed and endurance in
      persons with MS.

PMID- 22960050
TI  - Application of state-of-art sequencing technologies to indigenous food
      fermentations.
AB  - Fermented foods and beverages are an integral part of the human diet globally.
      Understanding the microbial interactions within these fermenting ecosystems is
      required to deliver safe products with desirable consumer properties, and
      moreover, maintenance of these traditions. Effective tools are required for
      documentation of cultures in traditional and artisanal fermented products, for
      sensory quality and safety improvements, in some cases for starter culture design
      for commercialization and potentially for supporting sustainable food systems.
      Here we trace the developments of sequence-based molecular technologies for
      investigating the diversity and functionality of microbiota in traditional or
      indigenous fermented foods and beverages. The opportunities of phylobiomics,
      metagenomics and metatranscriptomics to enrich our knowledge of fermenting
      microbial ecosystems are presented.

PMID- 22960052
TI  - Revisiting olfactory classical conditioning of the proboscis extension response
      in honey bees: a step toward standardized procedures.
AB  - The honey bee Apis mellifera has emerged as a robust and influential model for
      the study of classical conditioning thanks to the existence of a powerful
      Pavlovian conditioning protocol, the olfactory conditioning of the proboscis
      extension response (PER). In 2011, the olfactory PER conditioning protocol
      celebrated its 50 years since it was first introduced by Kimihisa Takeda in 1961.
      In this protocol, individually harnessed honey bees are trained to associate an
      odor with sucrose solution. The resulting olfactory learning is fast and induces
      robust olfactory memories that have been characterized at the behavioral,
      neuronal and molecular levels. Despite the success of this protocol for studying
      the bases of learning and memory at these different levels, innumerable
      procedural variants have arisen throughout the years, which render comparative
      analyses of behavioral performances difficult. Moreover, because even slight
      variations in conditioning procedures may introduce significant differences in
      acquisition and retention performances, we revisit olfactory PER conditioning and
      define here a standardized framework for experiments using this behavioral
      protocol. To this end, we present and discuss all the methodological steps and
      details necessary for successful implementation of olfactory PER conditioning.

PMID- 22960053
TI  - Computationally efficient simulation of extracellular recordings with
      multielectrode arrays.
AB  - In this paper we present a novel, computationally and memory efficient way of
      modeling the spatial dependency of measured spike waveforms in extracellular
      recordings of neuronal activity. We use compartment models to simulate action
      potentials in neurons and then apply linear source approximation to calculate the
      resulting extracellular spike waveform on a three dimensional grid of measurement
      points surrounding the neurons. We then apply traditional compression techniques
      and polynomial fitting to obtain a compact mathematical description of the
      spatial dependency of the spike waveform. We show how the compressed models can
      be used to efficiently calculate the spike waveform from a neuron in a large set
      of measurement points simultaneously and how the same procedure can be inversed
      to calculate the spike waveforms from a large set of neurons at a single
      electrode position. The compressed models have been implemented into an object
      oriented simulation tool that allows the simulation of multielectrode recordings
      that capture the variations in spike waveforms that are expected to arise between
      the different recording channels. The computational simplicity of our approach
      allows the simulation of a multi-channel recording of signals from large
      populations of neurons while simulating the activity of every neuron with a high
      level of detail. We have validated our compressed models against the original
      data obtained from the compartment models and we have shown, by example, how the
      simulation approach presented here can be used to quantify the performance in
      spike sorting as a function of electrode position.

PMID- 22960051
TI  - Rodent models of alcoholic liver disease: of mice and men.
AB  - Alcoholic liver disease (ALD) is a major cause of acute and chronic liver disease
      worldwide. The progressive nature of ALD is well described; however, the complex
      interactions under which these pathologies evolve remain to be fully elucidated.
      Clinically there are no clear biomarkers or universally accepted, effective
      treatment strategies for ALD. Experimental models of ALD are an important
      component in identifying underlying mechanisms of alcohol-induced injury to
      develop better diagnostic markers, predictors of disease progression, and
      therapeutic targets to manage, halt, or reverse disease progression. Rodents
      remain the most accessible model for studying ALD pathology. Effective rodent
      models must mimic the natural history of ALD while allowing examination of
      complex interactions between multiple hepatic, and non-hepatic, cell types in the
      setting of altered metabolic or oxidative/nitrosative stress, inflammatory
      responses, and sensitivity to cytotoxic stress. Additionally, mode and duration
      of alcohol delivery influence hepatic response and present unique challenges in
      understanding disease pathology. This review provides an overview of rodent
      models of ALD, their strengths and weaknesses relative to human disease states,
      and provides insight of the potential to develop novel rodent models to simulate
      the course of human ALD.

PMID- 22960055
TI  - Targeted nano analysis of water and ions using cryocorrelative light and scanning
      transmission electron microscopy.
AB  - Cryo fluorescence imaging coupled with the cryo-EM technique (cryo-CLEM) avoids
      chemical fixation and embedding in plastic, and is the gold standard for
      correlated imaging in a close to native state. This multi-modal approach has not
      previously included elementary nano analysis or evaluation of water content. We
      developed a new approach allowing analysis of targeted in situ intracellular ions
      and water measurements at the nanoscale (EDXS and STEM dark field imaging) within
      domains identified by examination of specific GFP-tagged proteins. This method
      allows both water and ions- fundamental to cell biology- to be located and
      quantified at the subcellular level. We illustrate the potential of this approach
      by investigating changes in water and ion content in nuclear domains identified
      by GFP-tagged proteins in cells stressed by Actinomycin D treatment and controls.
      The resolution of our approach was sufficient to distinguish clumps of condensed
      chromatin from surrounding nucleoplasm by fluorescence imaging and to perform
      nano analysis in this targeted compartment.

PMID- 22960054
TI  - The effect of smoking cessation pharmacotherapies on pancreatic beta cell
      function.
AB  - The goal of our study was to evaluate whether drugs currently used for smoking
      cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at
      nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a
      nAChR antagonist]) can affect beta cell function and determine the mechanism(s)
      of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine,
      varenicline and bupropion to determine their effects on beta cell function,
      mitochondrial electron transport chain enzyme activity and cellular/oxidative
      stress. Treatment of INS-1E cells with equimolar concentrations (1MUM) of three
      test compounds resulted in an ablation of normal glucose-stimulated insulin
      secretion by the cells. This disruption of normal beta cell function was
      associated with mitochondrial dysfunction since all three compounds tested
      significantly decreased the activity of mitochondrial electron transport chain
      enzyme activity. These results raise the possibility that the currently available
      smoking cessation pharmacotherapies may also have adverse effects on beta cell
      function and thus glycemic control in vivo. Therefore whether or not the use of
      nicotine replacement therapy, varenicline and bupropion can cause endocrine
      changes which are consistent with impaired pancreatic function warrants further
      investigation.

PMID- 22960056
TI  - Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload.
AB  - The inhibitory Smad7 acts as a critical suppressor of hepcidin, the major
      regulator of systemic iron homeostasis. In this study we define the mRNA
      expression of the two functionally related Smad proteins, Smad6 and Smad7, within
      pathways known to regulate hepcidin levels. Using mouse models for hereditary
      hemochromatosis (Hfe-, TfR2-, Hfe/TfR2-, Hjv- and hepcidin1-deficient mice) we
      show that hepcidin, Smad6 and Smad7 mRNA expression is coordinated in such a way
      that it correlates with the activity of the Bmp/Smad signaling pathway rather
      than with liver iron levels. This regulatory circuitry is disconnected by iron
      treatment of Hfe-/- and Hfe/TfR2 mice that significantly increases hepatic iron
      levels as well as hepcidin, Smad6 and Smad7 mRNA expression but fails to augment
      pSmad1/5/8 levels. This suggests that additional pathways contribute to the
      regulation of hepcidin, Smad6 and Smad7 under these conditions which do not
      require Hfe.

PMID- 22960057
TI  - Fifteen-year survey of one-stage latissimus dorsi muscle transfer for treatment
      of longstanding facial paralysis.
AB  - BACKGROUND: Neurovascular free muscle transfer is one of the main reconstructive
      options for established or long-standing facial paralysis. The two-stage gracilis
      muscle transfer combined with the cross-face nerve graft (two-stage method) has
      been supplanted by one-stage reconstruction using the latissimus dorsi muscle
      (LD) at our institution. This study retrospectively evaluated the results of one
      stage LD transfer. METHODS: Between September 1993 and December 2008, 344
      patients (133 males, 211 females; age range, 5-75 years) with unilateral facial
      paralysis underwent 351 one-stage LD transfers. Patients were evaluated with a
      custom grading scale. Differences in grading scale score were compared according
      to age, past surgical history and the duration from operation to neuromuscular
      recovery. RESULTS: Contraction of the transferred muscle was recognised in 305
      (87.0%) transfers. The duration until neuromuscular recovery ranged from 3 to 16
      months (average +/- standard deviation: 6.48 +/- 1.92 months). The grading scale
      was significantly lower in middle-age group than in younger and elder groups (P <
      0.01). Duration until neuromuscular recovery was significantly different when
      comparing the younger group and the oldest group. There was no difference in
      grading scale score or in duration until neuromuscular recovery when comparing
      the patients with a past surgical history and those without. The grading scale
      negatively correlated with the duration until neuromuscular recovery.
      CONCLUSIONS: The results are consistent and statistical analysis revealed the
      versatility of the one-stage LD transfer. Although we believe the two-stage
      method is still a good option for facial reanimation, the one-stage method is
      advantageous regarding the shorter period of recovery and little donor-site
      morbidity.

PMID- 22960058
TI  - Analysis of toxic effluents released from PVC carpet under different fire
      conditions.
AB  - A large number of investigations have been reported on minimising the PAH and
      PCDD/F yields during controlled combustion, such as incineration. This study is
      an attempt to quantify acute and chronic toxicants including PAH and PCDD/F in
      conditions relating to unwanted fires. This paper investigates distribution
      patterns of fire effluents between gas and aerosol phase, and the different
      particle size-ranges produced under different fire conditions. PVC carpet was
      selected as the fuel as a precursor for both PAH and PCDD/F. In order to generate
      fire effluents under controlled fire conditions, the steady-state tube furnace,
      was chosen as the physical fire model. Fire scenarios included oxidative
      pyrolysis, well-ventilated and under-ventilated fires. Fire effluent measurements
      included: carbon monoxide, carbon dioxide, hydrogen chloride, polycyclic aromatic
      hydrocarbons, chlorinated dibenzo-dioxins and furans and soot. The distribution
      patterns between gas and particle phase, and the size-ranges of the particles
      produced in these fires together with their chemical composition is also
      reported. Significant quantities of respirable submicron particles were detected,
      together with a range of PAHs. Lower levels of halogenated dioxins were detected
      in the fire residue compared with those found in other studies. Nevertheless, the
      findings do have implications for the health and safety of fire and rescue
      personnel, fire investigators, and other individuals exposed to the residue from
      unwanted fires.

PMID- 22960059
TI  - Biodegradation of benzene, toluene, ethylbenzene, and o-xylene by the bacterium
      Mycobacterium cosmeticum byf-4.
AB  - A new strain Mycobacterium cosmeticum byf-4 able to simultaneously degrade
      benzene, toluene, ethylbenzene, and o-xylene (BTE(o-)X) compounds has been
      isolated and identified previously in our laboratory. We further report here the
      extent of degradation of every BTE(o-)X component, and unravel the initial
      mechanism involved in BTE(o-)X degradation. This organism efficiently degrades
      all the BTE(o-)X components when these compounds are added either individually or
      as a composite mixture, and has a preference for toluene followed by benzene,
      ethylbenzene and then o-xylene. The significantly high carbon recovery indicated
      that the predominant fate for BTE(o-)X compounds was mineralization and
      incorporation into cell materials. The presence of BTE compounds in binary or
      ternary mixtures consistently had a negative effect on o-xylene degradation. The
      initial steps involved in the degradation of BTE(o-)X were investigated by
      isolation of metabolites and assay of reverse transcription RT-PCR. Isolation of
      metabolites suggested that the BTE(o-)X compounds were initially converted by a
      dioxygenase to their respective catechols. The gene sequence of the PCR amplicons
      revealed that this isolate contained a 454-bp toluene dioxygenase (TOD) fragment.
      The BTE(o-)X-specific induction of the genes encoding TOD was confirmed by RT-PCR
      analysis. These results indicated that TOD was possibly responsible for the
      initial steps of BTE(o-)X catabolism in M. cosmeticum byf-4.

PMID- 22960060
TI  - Blood levels of PCDDs, PCDFs, and coplanar PCBs in Yusho mothers and their
      descendants: association with fetal Yusho disease.
AB  - Maternal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) may result in adverse
      health effects in their children. In Japan in 1968, an accidental human exposure
      to rice oil contaminated with PCDDs, PCDFs, and PCBs, led to the development of
      Yusho disease. Yusho mothers delivered descendants with low birth weights and
      hyperpigmented skin and mucosa, which are characteristic of fetal Yusho disease
      (FYD). The Yusho cohort was used to evaluate the effect of maternal exposure to
      PCDDs, PCDFs, and PCBs on the development of FYD. Blood samples, obtained from 64
      Yusho mothers (117 descendants: 10 with FYD and 107 without FYD), were analyzed
      for congeners of seven PCDDs, 10 PCDFs, and four coplanar PCBs. We investigated
      the association between the maternal estimated blood levels of dioxins at
      delivery and the risk of fetal Yusho disease. We also studied the differences in
      dioxin blood levels in 24 mother-descendant pairs (5 with FYD and 19 without
      FYD). The estimated levels of total PCDD TEQ, total PCDF TEQ, total coplanar PCB
      TEQ, and total TEQ in the maternal blood at delivery were associated with
      significantly increased risk of FYD. The odds ratios, which present the risk of
      FYD for a 10-fold increase in blood dioxin, were largest for 1,2,3,6,7,8-HexaCDD
      (odds ratio=28.6, 95% confidence interval=1.67-489.9, p=0.02). The levels of
      1,2,3,6,7,8-HexaCDD in both the Yusho mothers and their descendants with FYD were
      higher than the levels in those without FYD. These findings suggest that
      1,2,3,6,7,8-HexaCDD is the most important causative congener for the development
      of FYD.

PMID- 22960061
TI  - Ni/Fe-supported over hydrotalcites precursors as catalysts for clean and
      selective oxidation of Basic Yellow 11: reaction intermediates determination.
AB  - In this work, Basic Yellow 11 (BY 11) was employed as model compound to study
      catalytic wet air oxidation as a pre-treatment step to the conventional
      biological oxidation. Ni and Fe catalysts supported over hydrotalcite (HT) were
      prepared by incipient wetness and excess impregnation to obtain catalysts with
      different metal loadings (from 1 to 10 wt.%). HTs were synthesized by co
      precipitation and characterized with XRD, X-ray fluorescence (XRF), BET,
      thermogravimetric analysis and SEM. Results showed that dye conversion increased
      with Ni and Fe content up to 7 wt.% and that the most effective catalyst were
      prepared by incipient wetness impregnation. The influence of metal loading in the
      catalyst, and the preparation method as well as the reaction conditions was
      investigated. A mechanism and reaction pathways for BY 11 during catalytic liquid
      phase oxidation have also been proposed.

PMID- 22960062
TI  - PTR-MS measurement of partition coefficients of reduced volatile sulfur compounds
      in liquids from biotrickling filters.
AB  - Biological air filtration for reduction of emissions of volatile sulfur compounds
      (e.g., hydrogen sulfide, methanethiol and dimethyl sulfide) from livestock
      production facilities is challenged by poor partitioning of these compounds into
      the aqueous biofilm or filter trickling water. In this study, Henry's law
      constants of reduced volatile sulfur compounds were measured for deionized water,
      biotrickling filter liquids (from the first and second stages of a two-stage
      biotrickling filter), and NaCl solutions by a dynamic method using Proton
      Transfer-Reaction Mass Spectrometry (PTR-MS) at a temperature range of 3-45
      degrees C. NaCl solutions were used to estimate salting-out constants up to an
      ionic strength of 0.7 M in order to evaluate the effect of ionic strength on
      partitioning between air and biofilter liquids. Thermodynamic parameters
      (enthalpy and entropy of phase exchange) were obtained from the measured
      partition coefficients as a function of temperature. The results show that the
      partition coefficients of organic sulfur compounds in the biotrickling filter
      liquids were generally very close to the corresponding partition coefficients in
      deionized water. Based on the estimated ionic strength of biofilter liquids, it
      is assessed that salting-out effects are of no importance for these compounds.
      For H(2)S, a higher enthalpy of air-liquid partitioning was observed for 2nd
      stage filter liquid, but not for 1st stage filter liquid. In general, the results
      show that co-solute effects for sulfur compounds can be neglected in numerical
      biofilter models and that the uptake of volatile sulfur compounds in biotrickling
      filter liquids cannot be increased by decreasing ionic strength.

PMID- 22960063
TI  - A comparison of the expression and contractile function of alpha1-adrenoceptors
      in seminal vesicle and vas deferens from normotensive and hypertensive rats.
AB  - Because hypertension related alterations occur in the properties of alpha(1)
      adrenoceptor in several mammalian tissues and hypertension may impact ejaculatory
      function, we investigated hypertension related alterations in the functional,
      biochemical and molecular properties of alpha(1)-adrenoceptor in the rat seminal
      vesicle and vas deferens. Spontaneous seminal emission in male spontaneously
      hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied
      during the 3-day observation period. The characteristics of alpha(1)-adrenoceptor
      in the seminal vesicle and epididymal and prostatic portion of vas deferens of
      the two strains were determined using an isolated muscle bath, radioligand
      receptor binding and real-time reverse transcription-polymerase chain reaction
      techniques. SHRs had significantly higher serum testosterone than WKY rats.
      However, the daily mean number of ejaculatory plugs emitted and their dry weight
      in SHRs were significantly lower than those in WKY rats. Although there was no
      significant difference in the properties of alpha(1)-adrenoceptor in the
      prostatic portion of vas deferens between SHRs and WKY rats, the maximum
      contractile responses to phenylephrine, total alpha(1)-adrenoceptor density and
      expression of alpha(1A)-adrenoceptor mRNA were significantly higher in the
      seminal vesicle and epididymal portion of vas deferens of SHRs vs. WKY rats. Our
      data demonstrate the presence of hypertension related alterations in serum
      testosterone and in alpha(1)-adrenergic responsiveness of the rat seminal vesicle
      and vas deferens and suggest that ejaculatory function in SHRs does not mirror
      these hypertension related alterations.

PMID- 22960064
TI  - Estradiol enhances effects of fructose rich diet on cardiac fatty acid
      transporter CD36 and triglycerides accumulation.
AB  - Fructose rich diet increases hepatic triglycerides production and has deleterious
      cardiac effects. Estrogens are involved in regulation of lipid metabolism as
      well, but their effects are cardio beneficial. In order to study effects of
      fructose rich diet on the main heart fatty acid transporter CD36 and the role of
      estrogens, we subjected ovariectomized female rats to the standard diet or
      fructose rich diet, with or without estradiol (E2) replacement. The following
      parameters were analyzed: feeding behavior, visceral adipose tissue mass, plasma
      lipids, cardiac CD36 expression, localization and insulin regulation, as well as
      the profile of cardiac lipids. Results show that fructose rich diet significantly
      increased plasma triglycerides and decreased plasma free fatty acid (FFA)
      concentration, while E2 additionally emphasized FFA decrease. The fructose diet
      increased cardiac plasma membrane content of CD36 in the basal and insulin
      stimulated states, and decreased its low density microsomes content. The E2 in
      fructose-fed rats raised the total cardiac protein content of CD36, its presence
      in plasma membranes and low density microsomes, and cardiac deposition of
      triglycerides, as well. Although E2 counteracts fructose in some aspects of lipid
      metabolism, and separately they have opposite cardiac effects, in combination
      with fructose rich diet, E2 additionally enhances CD36 presence in plasma
      membranes of cardiac cells and triglycerides accumulation, which paradoxically
      might promote deleterious effects of fructose diet on cardiac lipid metabolism.
      Taken together, the results presented in this work are of high importance for
      clinical administration of estrogens in females with a history of type 2
      diabetes.

PMID- 22960065
TI  - Letter concerning the paper by Finley and colleagues:
      dx.doi.org/10.1016/j.yrtph.2012.05.015.

PMID- 22960066
TI  - Timing abilities among children with developmental coordination disorders (DCD)
      in comparison to children with typical development.
AB  - Timing ability is essential for common everyday performance. The aim of the study
      was to compare timing abilities and temporal aspects of handwriting performance
      and relationships between these two components among children with Developmental
      Coordination Disorders (DCD) and a control group. Forty two children, 21
      diagnosed as DCD and 21 with typical development, aged 7-12, were matched for
      age, gender and school performed 14 tasks of the interactive metronome (IM) and
      three functional handwriting tasks on an electronic tablet that was part of a
      computerized system (ComPET--computerized penmanship evaluation tool). The IM
      supplies response time, while on-paper and in-air time per written stroke is
      received from the ComPET. Results indicated significant differences between the
      groups for both IM and handwriting tasks (ComPET). Linear regression indicated
      that the mean IM response time explained 37% of variance of the in-air time per
      stroke during a paragraph-copying task. Furthermore, based on one discriminate
      function including two measures reflected timing ability, 81% of all participants
      were correctly classified into groups. Study results strongly recommend
      consideration of the IM as an evaluation and intervention tool for children with
      DCD who are faced with timing deficits in their everyday functioning.

PMID- 22960067
TI  - Validation of a questionnaire to measure mastery motivation among Chinese
      preschool children.
AB  - The aim of this study was to validate a questionnaire on mastery motivation (task
      and effort) for use with Chinese preschool children in Hong Kong. A parent
      version and a teacher version were developed and evaluated. Participants included
      457 children (230 boys and 227 girls) aged four and five years old, their
      preschool teachers and their parents. Further, 44 children (39 boys and 5 girls)
      with developmental disabilities were recruited. The children were assessed on the
      cognitive sub-test of the Preschool Development Assessment Scale (PDAS). Their
      parents completed the task and effort motivation scales, as well as the Strengths
      and Difficulties Questionnaire (SDQ). Their teachers also completed the task and
      effort motivation scales. Rasch analysis results provided support for the
      unidimensionality of the parent and teacher versions of the two motivation
      scales. The parent and teacher versions of the two motivation scales correlated
      positively with the PDAS cognitive sub-test and the SDQ prosocial scale scores,
      and negatively with the SDQ total problem behavior scores. Children with
      developmental disabilities were assigned lower scores by their teachers and
      parents on the two motivation scales, compared with children with typical
      development. Reliability (Cronbach's Alpha) of the parent and teacher versions of
      the two motivation scales were above .70. The results suggested that the task and
      effort motivation scales were promising instruments for the assessment of
      motivation among Chinese preschool children.

PMID- 22960068
TI  - Effects of autistic traits on social and school adjustment in children and
      adolescents: the moderating roles of age and gender.
AB  - This study examined the associations between children's and adolescents' autistic
      like social deficits and school and social adjustment as well as the moderating
      roles of age and gender in these associations. The sample consisted of 1321
      students (48.7% boys) in Grade 1 to Grade 8 from northern Taiwan. Children's and
      adolescents' autistic-like social deficits were assessed using the Social
      Responsiveness Scale (SRS), and their school and social adjustment (i.e.,
      academic performance, negative attitudes toward schoolwork/teachers/classmates,
      behavioral problems at schools, negative peer relationships, and problems with
      peers) were assessed using the Social Adjustment Inventory for Children and
      Adolescents (SAICA). Both measures were completed by the mothers of the
      participants. Results from the linear mixed models demonstrated that autistic
      like social deficits were associated with poor academic performance, negative
      attitudes toward schoolwork, teachers, and classmates, behavioral problems at
      schools, negative peer relationships, and problematic peer interactions.
      Moreover, gender and/or age moderated the associations between autistic-like
      social deficits and school and social adjustment problems. For example, autistic
      like social deficits were more strongly related to negative school attitude,
      school social problems, and negative peer relationships in boys than in girls.
      Further, autistic-like social deficits were more strongly related to problems
      with peers in older girls than in older boys or younger children (regardless of
      gender). In conclusion, the present study suggests that autistic-like social
      deficits may place children and adolescents at increased risk for social and
      school maladjustment and that the extent of maladjustment may vary with the
      child's age and gender and the domains of adjustment under discussion.

PMID- 22960069
TI  - CRX variants in cone-rod dystrophy and mutation overview.
AB  - Mutations in the cone-rod homeobox gene (CRX) are associated with cone-rod
      dystrophy (CORD), Leber congenital amaurosis (LCA), and, in rare cases, retinitis
      pigmentosa (RP). In this study, three variations were detected in 3 of 130
      families with CORD, including two novel mutations, c.239A>G (p.Glu80Gly) and
      c.362C>T (p.Ala121Val). So far, 49 mutations in CRX were reported, affecting
      about 2.35% of LCA, 4.76% of CORD, and 0.80% of RP. These mutations can be
      classified as missense (38.78%), nonsense (4.08%), deletion (36.73%), insertion
      (16.33%), and indel (4.08%). They distributed in the three coding exons without
      mutation hot spots. No clear genotype-phenotype correlation could be established
      so far.

PMID- 22960070
TI  - Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative
      stress through maintaining hemoglobin stability.
AB  - The pathophysiology of oxidative hemolytic anemia is closely associated with
      hemoglobin (Hb) stability; however, the mechanism of how Hb maintains its
      stability under oxidative stress conditions of red blood cells (RBCs) carrying
      high levels of oxygen is unknown. Here, we investigated the potential role of
      peroxiredoxin II (Prx II) in preventing Hb aggregation induced by reactive oxygen
      species (ROS) using Prx II knockout mice and RBCs of patients with hemolytic
      anemia. Upon oxidative stress, ROS and Heinz body formation were significantly
      increased in Prx II knockout RBCs compared to wild-type (WT), which ultimately
      accelerated the accumulation of hemosiderin and heme-oxygenase 1 in the Prx II
      knock-out livers. In addition, ROS-dependent Hb aggregation was significantly
      increased in Prx II knockout RBCs. Interestingly, Prx II interacted with Hb in
      mouse RBCs, and their interaction, in particular, was severely impaired in RBCs
      of patients with thalassemia (THAL) and sickle cell anemia (SCA). Hb was bound to
      the decameric structure of Prx II, by which Hb was protected from oxidative
      stress. These findings suggest that Prx II plays an important role in preventing
      hemolytic anemia from oxidative stress by binding to Hb as a decameric structure
      to stabilize it.

PMID- 22960071
TI  - Biophysical properties of UDP-glucose:glycoprotein glucosyltransferase, a folding
      sensor enzyme in the ER, delineated by synthetic probes.
AB  - UDP-glucose:glycoprotein glucosyltransferase plays a key role in glycoprotein
      quality control in the endoplasmic reticulum, by virtue of its ability to
      discriminate folding states. Although lines of evidence have clarified the
      ability of UGGT to recognize a partially unfolded protein, its mechanistic
      rationale has been obscure. In this study, the substrate recognition mechanism of
      UGGT was studied using synthetic substrate of UGGT. Although UGGT has high extent
      of surface hydrophobicity, it clearly lacks property of typical molecular
      chaperones. Furthermore, it was revealed that the addition of the substrate
      caused secondary structure change of UGGT in a dose-dependent manner, resulting
      that the K(d) value of the UGGT-substrate interaction was estimated from
      theoretical formula based on 1:1 complexation between UGGT and the acceptor
      substrate. Moreover, the kinetic analysis of glucosyltransferase activity of UGGT
      elucidated Michaelis constant K(m) correctly.

PMID- 22960072
TI  - Effect of taurine on mRNA expression of thioredoxin interacting protein in Caco-2
      cells.
AB  - Taurine (2-aminoethanesulfonic acid), a sulfur-containing beta-amino acid, plays
      an important role in several essential biological processes; although, the
      underlying mechanisms for these regulatory functions remain to be elucidated,
      especially at the genetic level. We investigated the effects of taurine on the
      gene expression profile in Caco-2 cells using DNA microarray. Taurine increased
      the mRNA expression of thioredoxin interacting protein (TXNIP), which is involved
      in various metabolisms and diseases. beta-Alanine or gamma-aminobutyric acid
      (GABA), which are structurally or functionally related to taurine, did not
      increase TXNIP mRNA expression. These suggest the expression of TXNIP mRNA is
      induced specifically by taurine. beta-Alanine is also known to be a substrate of
      taurine transporter (TAUT) and competitively inhibits taurine uptake. Inhibition
      of taurine uptake by beta-alanine eliminated the up-regulation of TXNIP, which
      suggests TAUT is involved in inducing TXNIP mRNA expression. The up-regulation of
      TXNIP mRNA expression by taurine was also observed at the protein level.
      Furthermore, taurine significantly increased TXNIP promoter activity. Our present
      study demonstrated the taurine-specific phenomenon of TXNIP up-regulation, which
      sheds light on the physiological function of taurine.

PMID- 22960073
TI  - NADPH quinone oxidoreductase 1 mediates breast cancer cell resistance to
      thymoquinone-induced apoptosis.
AB  - Thymoquinone (TQ), a bioactive component of black caraway seed (Nigella sativa)
      oil, is reported to have antineoplastic properties. In this study we investigated
      the effect of TQ on a panel of human breast cancer cell lines. Cell viability
      assays showed that TQ killed T-47D, MDA-MB-231, and MDA-MB-468 cells via p53
      independent induction of apoptosis; however, MCF-7 cells were refractory to the
      cytotoxic action of TQ. Western Blot analysis showed that MCF-7 cells expressed
      high levels of cytoprotective NADPH quinone oxidoreductase 1 (NQO1), which was
      responsible for TQ-resistance since inhibition of NQO1 with dicoumarol rendered
      MCF-7 cells TQ-sensitive. These findings may be clinically important when
      considering TQ as a possible adjunct treatment for breast cancer since a high
      percentage of breast tumors express NQO1.

PMID- 22960074
TI  - Acid sensing ion channels regulate neuronal excitability by inhibiting BK
      potassium channels.
AB  - Acid sensing ion channels (ASICs), Ca(2+) and voltage-activated potassium
      channels (BK) are widely present throughout the central nervous system. Previous
      studies have shown that when expressed together in heterologous cells, ASICs
      inhibit BK channels, and this inhibition is relieved by acidic extracellular pH.
      We hypothesized that ASIC and BK channels might interact in neurons, and that
      ASICs may regulate BK channel activity. We found that ASICs inhibited BK currents
      in cultured wild-type cortical neurons, but not in ASIC1a/2/3 triple knockout
      neurons. The inhibition in the wild-type was partially relieved by a drop in
      extracellular pH to 6. To test the consequences of ASIC-BK interaction for
      neuronal excitability, we compared action potential firing in cultured cortical
      neurons from wild-type and ASIC1a/2/3 null mice. We found that in the knockout,
      action potentials were narrow and exhibited increased after-hyperpolarization.
      Moreover, the excitability of these neurons was significantly increased. These
      findings are consistent with increased BK channel activity in the neurons from
      ASIC1a/2/3 null mice. Our data suggest that ASICs can act as endogenous pH
      dependent inhibitors of BK channels, and thereby can reduce neuronal
      excitability.

PMID- 22960075
TI  - The glucagon-like peptide-1 receptor agonist Exendin 4 has a protective role in
      ischemic injury of lean and steatotic liver by inhibiting cell death and
      stimulating lipolysis.
AB  - Nonalcoholic fatty liver disease is an increasingly prevalent spectrum of
      conditions characterized by excess fat deposition within hepatocytes. Affected
      hepatocytes are known to be highly susceptible to ischemic insults, responding to
      injury with increased cell death, and commensurate liver dysfunction. Numerous
      clinical circumstances lead to hepatic ischemia. Mechanistically, specific means
      of reducing hepatic vulnerability to ischemia are of increasing clinical
      importance. In this study, we demonstrate that the glucagon-like peptide-1
      receptor agonist Exendin 4 (Ex4) protects hepatocytes from ischemia reperfusion
      injury by mitigating necrosis and apoptosis. Importantly, this effect is more
      pronounced in steatotic livers, with significantly reducing cell death and
      facilitating the initiation of lipolysis. Ex4 treatment leads to increased lipid
      droplet fission, and phosphorylation of perilipin and hormone sensitive lipase -
      all hallmarks of lipolysis. Importantly, the protective effects of Ex4 are seen
      after a short course of perioperative treatment, potentially making this
      clinically relevant. Thus, we conclude that Ex4 has a role in protecting lean and
      fatty livers from ischemic injury. The rapidity of the effect and the clinical
      availability of Ex4 make this an attractive new therapeutic approach for treating
      fatty livers at the time of an ischemic insult.

PMID- 22960077
TI  - Hearing loss in children treated for multidrug-resistant tuberculosis.
AB  - OBJECTIVE: The aminoglycosides and polypeptides are vital drugs for the
      management of multidrug-resistant (MDR) tuberculosis (TB). Both classes of drug
      cause hearing loss. We aimed to determine the extent of hearing loss in children
      treated for MDR-TB. METHODS: In this retrospective study, children (<15 years)
      admitted to Brooklyn Chest Hospital, Cape Town, South Africa, from January 2009
      until December 2010, were included if treated for MDR-TB with injectable drugs.
      Hearing was assessed and classified using audiometry and otoacoustic emissions.
      RESULTS: Ninety-four children were included (median age: 43 months). Of 93
      tested, 28 (30%) were HIV-infected. Twenty-three (24%) children had hearing loss.
      Culture-confirmed, as opposed to presumed, diagnosis of TB was a risk factor for
      hearing loss (OR: 4.12; 95% CI: 1.13-15.0; p = 0.02). Seven of 11 (64%) children
      classified as having hearing loss using audiometry had progression of hearing
      loss after finishing the injectable drug. CONCLUSIONS: Hearing loss is common in
      children treated for MDR-TB. Alternative drugs are required for the treatment of
      paediatric MDR-TB.

PMID- 22960076
TI  - Spontaneous latency in a rabbit model of pulmonary tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is an
      exquisitely adapted human pathogen capable of surviving for decades in the lungs
      of immune-competent individuals in the absence of disease. The World Health
      Organization estimates that 2 billion people have latent TB infection (LTBI),
      defined by a positive immunological response to Mtb antigens, with no clinical
      signs of disease. A better understanding of host and pathogen determinants of
      LTBI and subsequent reactivation would benefit TB control efforts. Animal models
      of LTBI have been hampered generally by an inability to achieve complete
      bacillary clearance. Herein, we have characterized a rabbit model of LTBI in
      which, similar to most humans, complete clearance of pulmonary Mtb infection and
      pathological characteristics occurs spontaneously. The evidence that Mtb-CDC1551
      infected rabbits achieve LTBI, rather than sterilization, is based on the ability
      of the bacilli to be reactivated after immune suppression. These rabbits showed
      early activation of T cells and macrophages and an early peak in the TNFalpha
      level, which decreased in association with clearance of bacilli from the lungs.
      In the absence of sustained tumor necrosis factor-alpha production, no necrosis
      was seen in the evolving lung granulomas. In addition, bacillary control was
      associated with down-regulation of several metalloprotease genes and an absence
      of lung fibrosis. This model will be used to characterize molecular markers of
      protective immunity and reactivation.

PMID- 22960079
TI  - Pneumococcal meningitis in cirrhotics: distinctive findings of presentation and
      outcome.

PMID- 22960078
TI  - The effect of staphylococcal cassette chromosome mec (SCCmec) type on clinical
      outcomes in methicillin-resistant Staphylococcus aureus bacteremia.
AB  - OBJECTIVES: The impact of staphylococcal cassette chromosome mec (SCCmec) type on
      mortality in methicillin-resistant Staphylococcus aureus (MRSA) infections
      remains unclear. The objective of this study was to determine the association
      between SCCmec type and mortality in MRSA bacteremia. METHODS: A cohort study of
      patients who were hospitalized with MRSA bacteremia was conducted within a
      university health system. A multivariable logistic regression model was developed
      to evaluate the association of SCCmec type with 30-day in-hospital mortality.
      RESULTS: Thirty-four of a total of 184 patients with MRSA bacteremia died,
      resulting in a mortality rate of 18.5%. Adjusted risk factors for 30-day
      mortality included APRDRG Risk of Mortality score (odds ratio [OR], 5.33; 95%
      confidence interval [CI], 2.28-12.4; P<0.001), white blood cell count (OR, 1.09;
      95% CI, 1.03-1.15; P=0.002), and malignancy (OR, 3.25; 95% CI, 1.17-9.02;
      P=0.02). On multivariable analyses, SCCmec II was not significantly associated
      with mortality in patients with MRSA bacteremia (OR, 1.85; 95% CI, 0.69-4.92;
      P=0.22). CONCLUSIONS: Mortality in MRSA bacteremia was independent of SCCmec
      type. SCCmec type II is most likely a marker for disease severity rather than a
      direct mediator of mortality. Further research is needed to elucidate the factors
      associated with poor clinical outcomes in MRSA infections.

PMID- 22960080
TI  - Antitumor and immunomodulatory activity of polysaccharides from the root of
      Limonium sinense Kuntze.
AB  - Limonium sinense (Girard) Kuntze is a traditional Chinese folk medicine used for
      the treatment of fever, hemorrhage, hepatitis and other disorders. The study
      focused on the antitumor and immunomodulatory activities of L. sinense
      polysaccharides (LSP) which was obtained from the root of the plant. The
      antitumor effects of only LSP and LSP in combination with 5-fluorouracil (5-FU)
      were both evaluated with Heps-bearing tumor mice models. In addition, the
      macrophage phagocytosis assay, splenocyte proliferation and cytokines production
      tests were used to assess the immunomodulatory activities of LSP. The results
      revealed that the LSP (at the dose of 200 and 400 mg/kg) had an obvious
      inhibition on the growth of transplanted mouse tumor. It also exhibited a
      significant synergistic effect of antitumor activity when combined with 5-FU
      (p<0.05). Furthermore, the LSP (at the dose of 100 and 200 mg/kg) remarkably
      improved macrophage phagocytosis function in immune suppressed mice. In addition,
      LSP (at the dose of 50-200 MUg/ml) showed significant synergistic effects on ConA
      stimulated proliferation and IFN-gamma and IL-2 production of splenocyte in vitro
      (p<0.05). These findings suggest that LSP had clear antitumor activity which
      might be related to its regulation of immune function in mice.

PMID- 22960081
TI  - Reversal alterations of amplitude of low-frequency fluctuations in early and late
      onset, first-episode, drug-naive depression.
AB  - BACKGROUND: It is unclear how patients with early onset depression (EOD) and late
      onset depression (LOD) differ at the neural level. Using amplitude of low
      frequency fluctuations (ALFF) approach, we are to test the hypothesis of the
      different abnormal neural activities between patients with EOD and LOD. METHODS:
      Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS)
      and 15 old HS were enrolled in the study. ALFF approach was employed to analyze
      the images. RESULTS: ANOVA analysis revealed widespread differences in ALFF
      values among the four groups throughout frontal, parietal, temporal, occipital
      cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had
      higher ALFF in bilateral precuneus, superior medial frontal gyrus and superior
      frontal gyrus, and lower ALFF in left brainstem and left superior temporal gyrus.
      Compared to young HS, lower ALFF in left superior/inferior temporal gyrus, left
      lingual gyrus and right middle occipital gyrus and higher ALFF in left medial
      frontal gyrus and bilateral superior frontal gyrus were seen in the EOD group; in
      contrast, in the LOD group, lower ALFF in bilateral superior frontal gyrus and
      higher ALFF in left superior temporal gyrus were observed. Further ROC analysis
      suggested that the mean ALFF values in the bilateral superior frontal gyrus and
      left superior temporal gyrus could serve as markers to separate patients with EOD
      from individuals with LOD. CONCLUSIONS: Patients with EOD and LOD exhibit
      reversal pattern of abnormal ALFF in bilateral superior frontal gyrus and left
      superior temporal gyrus.

PMID- 22960082
TI  - Altered gene expression in the prefrontal cortex of young rats induced by the
      ADHD drug atomoxetine.
AB  - Atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, is a non
      stimulant approved for the treatment of attention deficit/hyperactivity disorder
      (ADHD). Little is known about the molecular basis for its therapeutic effect. The
      objective of this animal study was to determine alterations in gene expression
      patterns in the prefrontal cortex after long-term administration of atomoxetine.
      Rats were treated for 21 days during childhood and early adolescent stages of
      development with a once-daily oral application of 0.05 g/kg atomoxetine, which
      resulted in plasma levels similar to those described in children. A whole genome
      RNA-microarray of rat prefrontal cortical gene expression after administration of
      atomoxetine versus sterile water revealed an mRNA increase in 114 genes (>=2
      fold) while 11 genes were down-regulated (<=0.5-fold). By applying quantitative
      real-time PCR (qRT-PCR) and Western Blot we confirmed a significant increase in
      the expression of GABA A receptor subunits as well as ubiquinol-cytochrome c
      reductase complex core protein 2 (Uqcrc2). SNAP-25 (synaptosomal-associated
      protein of 25 kDa), which is an ADHD candidate gene and an important vesicle
      protein involved in axonal growth, synaptic plasticity and regulation of
      neurotransmitter release was also significantly upregulated on RNA- and protein
      level after atomoxetine treatment. In summary, we could show that long-term
      treatment with the ADHD drug atomoxetine induces the regulation of several genes
      in the prefrontal cortex of young rats. Especially the increased expression of
      SNAP-25 and GABA-A receptor subunits may indicate additional active therapeutic
      mechanisms for atomoxetine.

PMID- 22960083
TI  - Semantic processing impairment in individuals with schizotypal personality
      disorder features: a preliminary event-related potential study.
AB  - OBJECTIVE: This study aimed to examine semantic processing features in
      individuals with and without schizotypal personality disorder (SPD) features.
      METHODS: An implicit semantic task was used to examine the automatic spreading
      semantic activation process which is relatively free from the influence of
      attention. An explicit semantic task was used to examine the controlled semantic
      processing which requires high involvement of attention. Individuals with stable
      SPD features (n=17) were those who scored higher than 36 on the schizotypal
      personality questionnaire (SPQ) at two time points. Individuals with unstable SPD
      features (n=15) were defined as participants who scored higher than 36 at the
      baseline time point but lower than 36 at the second time point. Their
      performances in the two semantic tasks were then compared to 17 individuals
      without SPD features (scoring below 36 at both time points). Event-related
      potentials (ERP) were recorded when participants were performing the two tasks.
      RESULTS: Behavioral data, early ERP components and N400s were analyzed in each
      experiment. No between-group difference was observed in the implicit semantic
      task. In the explicit semantic task, the differences involved only the N400
      component. When compared to the group without SPD features, participants with
      stable and unstable SPD features showed enhanced N400 effects (difference wave),
      while there was no difference between the two groups with SPD features. Moreover,
      the larger N400 effects were found to be due to less negative N400 amplitudes to
      related target words. CONCLUSION: These findings suggest that individuals with
      SPD features were impaired in processing of context-related stimuli. The
      inhibition function to contextually unrelated materials in participants with SPD
      features appeared intact.

PMID- 22960084
TI  - Structural and diffusion MRI measures of the hippocampus and memory performance.
AB  - Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures
      of the hippocampus have been reported in patients with Alzheimer's disease. We
      examined the association between hippocampal volumes, DTI measures of the
      hippocampus and memory performance in 892 non-demented persons (age >= 55 years)
      across different age groups. Hippocampal volume was segmented on 3D volumetric
      MRI scans. The segmentations were co-registered to mean diffusivity (MD) and
      fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements.
      Higher MD of the hippocampus was associated with impaired verbal memory
      performance. In all persons >= 55 years, a higher MD of the hippocampus was
      associated with a worse memory performance. Hippocampal volumes were very weakly
      positively associated with delayed recall and only in persons > 65 years. FA of
      the hippocampus was not associated with memory performance. Follow-up studies
      will be needed to determine whether higher MD of hippocampus at younger ages
      could be an earlier marker of incident Alzheimer's disease than hippocampal
      volume.

PMID- 22960085
TI  - In vivo assessment of use-dependent brain plasticity--beyond the "one trick pony"
      imaging strategy.
AB  - This article has been written as a comment to Dr Thomas and Dr Baker's article
      "Teaching an adult brain new tricks: A critical review of evidence for training
      dependent structural plasticity in humans". We deliberately expand on the key
      question about the biological substrates underlying use-dependent brain
      plasticity rather than reiterating the authors' main points of criticism already
      addressed in more general way by previous publications in the field. The focus
      here is on the following main issues: i) controversial brain plasticity findings
      in voxel-based morphometry studies are partially due to the strong dependency of
      the widely used T1-weighted imaging protocol on varying magnetic resonance
      contrast contributions; ii) novel concepts in statistical analysis allow one to
      directly infer topological specificity of structural brain changes associated
      with plasticity. We conclude that iii) voxel-based quantification of relaxometry
      derived parameter maps could provide a new perspective on use-dependent
      plasticity by characterisation of brain tissue property changes beyond the
      estimation of volume and cortical thickness changes. In the relevant sections we
      respond to the concerns raised by Dr Thomas and Dr Baker from the perspective of
      the proposed data acquisition and analysis strategy.

PMID- 22960086
TI  - Recovery of the default mode network after demanding neurofeedback training
      occurs in spatio-temporally segregated subnetworks.
AB  - The default mode (DM) network is a major large-scale cerebral network that can be
      identified with functional magnetic resonance imaging (fMRI) during resting
      state. Most studies consider functional connectivity networks as stationary
      phenomena. Consequently, the transient behavior of the DM network and its
      subnetworks is still largely unexplored. Most functional connectivity fMRI
      studies assess the steady state of resting without any task. To specifically
      investigate the recovery of the DM network during the transition from activation
      to rest, we implemented a cognitively demanding real-time fMRI neurofeedback task
      that targeted down-regulation of the primary auditory cortex. Each of twelve
      healthy subjects performed 16 block-design fMRI runs (4 runs per day repeated on
      4 days) resulting 192 runs in total. The analysis included data-driven
      independent component analysis (ICA) and high-resolution latency estimation
      between the four components that corresponded to subnetworks of the DM network.
      These different subnetworks reemerged after regulation with an average time lag
      or 3.3s and a time lag of 4.4s between the first and fourth components; i.e., the
      DM recovery first shifts from anterior to posterior, and then gradually focuses
      on the ventral part of the posterior cingulate cortex, which is known to be
      implicated in internally directed cognition. In addition, we found less
      reactivation in the early anterior subnetwork as regulation strength increased,
      but more reactivation with larger regulation for the late subnetwork that
      encompassed the ventral PCC. This finding confirms that the level of task
      engagement influences inversely the subsequent recovery of regions related to
      attention compared to those related to internally directed cognition.

PMID- 22960088
TI  - Evaluation of a generic RT-nested-PCR for detection of flaviviruses in suspected
      fatal cases of dengue infection, Rio de Janeiro, Brazil.
AB  - Flaviviruses are significant causes of disease worldwide and can be classified
      serologically into several antigenic complexes. The purpose of the present study
      was to evaluate the effectiveness of a generic RT-nested-PCR for detection of
      flavivirus during a dengue outbreak in Brazil in 2008. A total of 105 serum
      samples were collected from patients with fatal outcome and examined by generic
      RT-PCR, conventional RT-PCR, and IgM serology. The generic RT-PCR confirmed 19 of
      105 (18%) cases. Conventional RT-PCR performed on 105 serum samples detected 45
      (42.8%) dengue virus infections. The IgM serology confirmed 44 of 102 (43.1%)
      cases. The infecting serotype was identified by generic RT-PCR in 19 cases (18
      DENV-2 and 1 DENV-3) and by conventional RT-PCR in 45 cases (40 DENV-2 and 5 DENV
      3). In addition, we analyzed the performance of the generic and conventional RT
      PCRs and IgM serology on serum samples stratified by the day of onset of
      symptoms. Our results indicate that different methods should be included in
      flavivirus surveillance programs, including virological and serological
      approaches.

PMID- 22960089
TI  - Evaluation of the SD Bioline Norovirus rapid immunochromatography test using
      fecal specimens from Korean gastroenteritis patients.
AB  - The analytical and clinical performance of a new rapid immunochromatography test,
      the SD Bioline Norovirus test, was evaluated for the detection of human norovirus
      in fecal specimens. The analytical performance studies were performed for
      detection limit, reproducibility, cross-reactivity, and interference. For
      comparison, 92 norovirus-positive stool samples and 126 norovirus-negative
      samples for which the results were confirmed by 2 different real-time PCR kits
      were used. The rapid immunochromatography test detected the equivalent of
      4.48*10(6) copies/mL of the norovirus genome in stool samples. On performing the
      repeatability/reproducibility test, samples above this concentration all provided
      positive results (100%) and 97.8% of the samples slightly below this
      concentration (2.45*10(6) copies/mL) provided negative results. No cross
      reactivity or interference was detected. Positive percent agreement
      (sensitivity), negative percent agreement (specificity), and overall percent
      agreement of the rapid immunochromatography test compared with testing by real
      time PCR were 90.2%, 100%, and 95.9%, respectively. In addition, the rapid
      immunochromatography test was completed within 20 min. The SD Bioline Norovirus
      test was, therefore, easier and more rapid to perform and showed excellent
      reproducibility, no cross-reactivity, no interference, and high agreement
      compared with real-time PCR. Thus, this test is useful for rapid screening to
      identity norovirus infection.

PMID- 22960090
TI  - The relationship of tibial bone perfusion to pain in knee osteoarthritis.
AB  - OBJECTIVE: To confirm altered perfusion within tibial bone marrow lesions (BMLs)
      and improve our understanding on the relationship between BMLs and pain in knee
      osteoarthritis (OA). METHODS: Participants with moderate to severe knee OA were
      recruited and pain was assessed using the pain subscale of the Western Ontario
      and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were
      identified and graded on magnetic resonance imaging (MRI) proton density-weighted
      (PDW) fat suppressed images. A pharmacokinetic model was used to analyze
      perfusion parameters on dynamic contrast enhanced (DCE) MRI which represent
      transfer rates in and out of the BMLs. The relation between perfusion and pain
      was evaluated using multivariable linear regression after adjustment for BML
      grade, age, gender and body mass index (BMI). RESULTS: There were 37 participants
      (mean age 64.9 years, range 46-86) with radiographic Kellgren and Lawrence grades
      of 3 and 4 in the study knee; 75.6% had BMLs that were classified grades 1 and 2.
      The mean WOMAC pain score was 10.3 (0-20 scale). There was a significant
      correlation between BML K(el) (rate of contrast elimination) and BML grade (P =
      0.001 univariate, P = 0.002 multivariate analyses), although we did not
      demonstrate any significant multivariate association between BML perfusion and
      pain. We also found an inverse relationship between pain at sleep and BML grade
      (P < 0.05). CONCLUSIONS: The absence of any significant association between bone
      perfusion and pain implies that the relationship of tibial BMLs to pain in OA is
      still incompletely understood. BMLs are just one component of the whole knee
      joint and are formed from various causes, all of which interact and collectively
      contribute to the genesis of pain in OA.

PMID- 22960091
TI  - Knee cartilage defects in a sample of older adults: natural history, clinical
      significance and factors influencing change over 2.9 years.
AB  - OBJECTIVE: To describe the natural history of knee cartilage defects, and their
      relationship to cartilage volume loss and risk of knee replacement in a
      longitudinal study of older adults. DESIGN: 395 randomly selected older adults
      (mean age 62.7 years) had magnetic resonance imaging of their right knee at
      baseline and approximately 2.9 years later to determine cartilage defect grade (0
      4), cartilage volume, medial and lateral tibial bone size, and presence of bone
      marrow lesions (BMLs). Height, weight, body mass index (BMI) and radiographic
      osteoarthritis were measured by standard protocols. RESULTS: At baseline higher
      grade cartilage defects (grade >=2) were significantly associated with age, BMI,
      lateral tibial bone size, BMLs, and radiographic osteoarthritis. Over 2.9 years,
      the average defect score increased statistically significantly in all
      compartments; however, the majority of defects remained stable and regression of
      defects was rare. Baseline factors associated with increase in defect score over
      2.9 years were radiographic osteoarthritis, tibial bone size, BMI and being
      female. In multivariate analysis, baseline cartilage defect grade predicted
      cartilage volume loss at the medial tibia, lateral tibia and patella over 2.9
      years (beta = -1.78% to -1.27% per annum per 1 grade increase, P < 0.05 for all
      comparisons), and risk of knee replacement over 5 years (odds ratio (OR) = 1.73
      per 1 grade increase, P = 0.001). CONCLUSION: Knee cartilage defects in older
      adults are common but less likely to regress than in younger life. They
      independently predict cartilage volume loss and risk of knee replacement,
      suggesting they are potential targets for intervention.

PMID- 22960087
TI  - Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI.
AB  - The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important
      for normal memory function. Specifically, perirhinal cortex is involved in the
      detection of novel objects and manifests neurofibrillary tangles in Alzheimer's
      disease very early in disease progression. We scanned ex vivo brain hemispheres
      at standard resolution (1 mm * 1 mm * 1 mm) to construct pial/white matter
      surfaces in FreeSurfer and scanned again at high resolution (120 MUm * 120 MUm *
      120 MUm) to determine cortical architectural boundaries. After labeling
      perirhinal area 35 in the high resolution images, we mapped the high resolution
      labels to the surface models to localize area 35 in fourteen cases. We validated
      the area boundaries determined using histological Nissl staining. To test the
      accuracy of the probabilistic mapping, we measured the Hausdorff distance between
      the predicted and true labels and found that the median Hausdorff distance was
      4.0mm for the left hemispheres (n=7) and 3.2mm for the right hemispheres (n=7)
      across subjects. To show the utility of perirhinal localization, we mapped our
      labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and
      found decreased cortical thickness measures in mild cognitive impairment and
      Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our
      ex vivo probabilistic mapping of the perirhinal cortex provides histologically
      validated, automated and accurate labeling of architectonic regions in the medial
      temporal lobe, and facilitates the analysis of atrophic changes in a large
      dataset for earlier detection and diagnosis.

PMID- 22960092
TI  - Synovial inflammation, immune cells and their cytokines in osteoarthritis: a
      review.
AB  - OBJECTIVE: Although osteoarthritis (OA) is considered a non-inflammatory
      condition, it is widely accepted that synovial inflammation is a feature of OA.
      However, the role of immune cells and their cytokines in OA is largely unknown.
      This narrative systematic review summarizes the knowledge of inflammatory
      properties, immune cells and their cytokines in synovial tissues (STs) of OA
      patients. DESIGN: Broad literature search in different databases was performed
      which resulted in 100 articles. RESULTS: Of 100 articles 33 solely investigated
      inflammation in OA ST with or without comparison with normal samples; the
      remaining primarily focussed on rheumatoid arthritis (RA) ST. Studies
      investigating different severity stages or cellular source of cytokines were
      sparse. OA ST displayed mild/moderate grade inflammation when investigated by
      means of haematoxylin and eosin (H&E) staining. Most frequently found cells types
      were macrophages, T cells and mast cells (MCs). Overall the number of cells was
      lower than in RA, although the number of MCs was as high as or sometimes even
      higher than in RA ST. Cytokines related to T cell or macrophage function were
      found in OA ST. Their expression was overall higher than in normal ST, but lower
      than in RA ST. Their cellular source remains largely unknown in OA ST.
      CONCLUSION: Inflammation is common in OA ST and characterized by immune cell
      infiltration and cytokine secretion. This inflammation seems quantitatively and
      qualitatively different from inflammation in RA. Further research is needed to
      clarify the role of inflammation, immune cells and their cytokines in the
      pathogenesis of OA.

PMID- 22960093
TI  - Osteoarthritis 2012 year in review: rehabilitation and outcomes.
AB  - Recent scientific advances in the treatment of hip and knee osteoarthritis (OA)
      relating to education, exercise, weight control and passive non-pharmacological
      and non-surgical treatments such as manual therapy, orthoses/orthotics and other
      aids are described. METHODS: A systematic literature search was performed in
      Medline from July 2011 to 10 April 2012 using the terms 'osteoarthritis, knee',
      'osteoarthritis, hip' rehabilitation, physical therapy, exercise therapy and
      preoperative intervention; both as text words and as MeSH terms where possible.
      Trials evaluating rehabilitation interventions were included if they were
      randomized controlled trials (RCTs) or systematic reviews. Outcome papers were
      identified by combining the initial search with the terms 'outcome', 'measure*',
      'valid*', 'reliabil*' or 'responsiveness'. Outcome studies were included if they
      contributed methodologically to advancing outcome measurement. RESULTS: The
      literature search identified 550 potentially relevant papers. Seventeen RCTs on
      rehabilitation were selected and the results from these were supported by six
      systematic reviews. Sixteen outcomes papers were considered relevant, but did not
      add significantly to current knowledge about outcome measures in OA and so, were
      not included. CONCLUSION: The current research focus on non-pharmacological and
      non-surgical treatments for hip and/or knee OA, when combined in systematic
      reviews, is improving the available evidence to identify best practice treatment.
      Education, exercise and weight loss are effective in the long term and supported
      as cost-effective first-line treatments.

PMID- 22960094
TI  - Comment on the role of 3T diffusion tensor imaging in glaucoma.

PMID- 22960095
TI  - Ethambutol-induced optic neuropathy: a nationwide population-based study from
      Taiwan.
AB  - AIM: To investigate the risk factors and comorbidities associated with ethambutol
      induced optic neuropathy (EON). METHOD: Using the Taiwan Longitudinal Health
      Insurance Database, we conducted a study within a nationwide representative
      cohort of patients treated with EMB. We identified 231 patients newly diagnosed
      with EON between 2000 and 2008, and 924 control subjects. Adjusted OR by
      estimating the risk of EON in relation to comorbidities and EMB prescription
      protocol was determined. RESULTS: Compared with the control group, EON patients
      were at risk with older age, hypertension (adjusted OR=1.62, 95% CI 1.16 to 2.26)
      and renal diseases (without end-stage renal diseases (ESRD), adjusted OR=2.11,
      95% CI 1.02 to 4.35; with ESRD, adjusted OR=3.73, 95% CI 1.79 to 7.74). Patients
      with an EMB prescription duration longer than 3 months were not at elevated risk
      compared with those whose prescription less than 3 months (OR=1.35, 95% CI 0.99
      to 1.83, adjusted for age, sex, hypertension and renal diseases). Patients whose
      average daily dose was greater than 1200 mg, compared with the other two groups
      (800~1199 mg, less than 800 mg) were not at increased risk for EON. CONCLUSIONS:
      Age, hypertension and renal diseases are risk factors for EON in the Taiwanese
      population.

PMID- 22960096
TI  - Population data for 17 Y-chromosome STRs in a sample from Apulia (Southern
      Italy).
AB  - The 17 Y-STR loci included in the AmpFLSTR Yfiler PCR Amplification Kit were
      analyzed in 98 unrelated healthy males from Apulia (Southern Italy). A total of
      97 different haplotypes were identified, of which 96 haplotypes were unique and 1
      occurred twice. Allele frequencies for each Y-STR locus in pooled sample and
      estimated value of gene diversity (GD) were evaluated. The lowest value of GD was
      observed for DYS392 (0.126) and the highest one (0.936) for DYS385. The HD
      (haplotype diversity) for the studied Y-STR set showed a value of 0.9994, with an
      HMP (haplotype match probability) value of 0.0006, while the overall DC was
      98.98%. Microvariant alleles were found for the DYS458 and DYS385 markers and
      sequenced. Furthermore, Phi(st)-based genetic distance computation and pair-wise
      analysis of molecular variance (AMOVA) test were carried out. When comparing our
      population with the Apulia sample previously investigated, the AMOVA analysis
      detected no evidence for significant differentiation. The comparison with all
      Italian populations submitted to the YHRD website showed no relevant differences
      with all Southern Italian populations (San Giorgio La Molara, Belvedere, Trapani
      and Catania) and significant genetic deviation with all Northern Italian
      populations (Udine, Biella, La Spezia, Modena, Ravenna, Marche and North
      Sardinia). Moreover, the other populations and meta-populations belonging to the
      whole Mediterranean area (Croatia, Macedonia, Albania, Greece, Turkey, Israel,
      Libya, Tunisia, Algeria, Morocco and Spain) were different from our Apulia
      sample. The data were submitted to YHRD.

PMID- 22960097
TI  - Averaging time, desaturation level, duration and extent.
AB  - BACKGROUND: Pulse oximeter saturation values are usually obtained by averaging
      over preceding measurements. This study investigates the dynamics between the
      averaging time and desaturation level, duration and extent. METHODS AND RESULTS:
      Prospective observational study of 15 preterm infants. Oxygen saturation was
      recorded for 168 h using a pulse oximeter. The raw red-to-infrared data were
      reprocessed using seven different averaging times to determine the number of
      desaturations below four thresholds and for seven different minimal desaturation
      durations. The total number of desaturations <80% was 339 with an averaging time
      of 16 s and 1958 with an averaging time of 3 s (minimal event duration >0 s).
      There was a significantly lower pulse oximeter saturation nadir with the shorter
      averaging time, while the maximum duration was significantly longer when using a
      16 s averaging time. CONCLUSIONS: When using pulse oximeters, more attention
      should be given to averaging time and duration of desaturations.

PMID- 22960098
TI  - The evidence for non-invasive ventilation in the preterm infant.

PMID- 22960099
TI  - Prophenoloxidase system and its role in shrimp immune responses against major
      pathogens.
AB  - The global shrimp industry still faces various serious disease-related problems
      that are mainly caused by pathogenic bacteria and viruses. Understanding the host
      defense mechanisms is likely to be beneficial in designing and implementing
      effective strategies to solve the current and future pathogen-related problems.
      Melanization, which is performed by phenoloxidase (PO) and controlled by the
      prophenoloxidase (proPO) activation cascade, plays an important role in the
      invertebrate immune system in allowing a rapid response to pathogen infection.
      The activation of the proPO system, by the specific recognition of microorganisms
      by pattern-recognition proteins (PRPs), triggers a serine proteinase cascade,
      eventually leading to the cleavage of the inactive proPO to the active PO that
      functions to produce the melanin and toxic reactive intermediates against
      invading pathogens. This review highlights the recent discoveries of the critical
      roles of the proPO system in the shrimp immune responses against major pathogens,
      and emphasizes the functional characterizations of four major groups of genes and
      proteins in the proPO cascade in penaeid shrimp, that is the PRPs, serine
      proteinases, proPO and inhibitors.

PMID- 22960100
TI  - Purification and characterization of a novel peptide with inhibitory effects on
      colitis induced mice by dextran sulfate sodium from enzymatic hydrolysates of
      Crassostrea gigas.
AB  - The anti-inflammatory activity of purified peptides from Crassostrea gigas (C.
      gigas) hydrolysates was studied. To prepare hydrolysates from C. gigas, we used
      eight different proteinases and the anti-inflammatory activities were determined
      using a nitric oxide (NO) assay in RAW264.7 cells. Among the hydrolysates,
      Protamex hydrolysates showed the highest anti-inflammatory activity. We separated
      and purified the total hydrolysate using an ultrafiltration membrane system and
      consecutive chromatographic methods. Finally, we obtained a peptide with the
      following sequence: Gln-Cys-Gln-Cys-Ala-Val-Glu-Gly-Gly-Leu at N-terminal
      position. The anti-inflammatory peptide purified from C. gigas inhibited NO
      production by 72.2% compared to the lipopolysaccharide (LPS) treated group. In
      addition, the Protamex hydrolysates from C. gigas showed decreased serum IgE
      levels and increased spleen CD4(+)/CD8(+) levels on dextran sulfate sodium (DSS)
      induced colitis in mice. These results suggest the peptide and hydrolysate from
      C. gigas possess potent anti-inflammatory effect.

PMID- 22960101
TI  - Pattern recognition receptors acting in innate immune system of shrimp against
      pathogen infections.
AB  - Invertebrates, including shrimp, have developed very complicated innate immune
      system against pathogens. Much work has been performed on the innate immunity of
      shrimp, including immune recognition, signal transduction, effector molecules and
      antiviral responses due to its great economic value. Pattern recognition is the
      first step of innate immunity. Pattern recognition receptors (PRRs) sense the
      presence of infection and activate immune responses. The studies on shrimp PRRs
      revealed the recognition mechanism of shrimp at a certain degree. To date, 11
      types of pattern recognition receptors (PRRs) have been identified in shrimp,
      namely, beta-1,3-glucanase-related proteins, beta-1,3-glucan-binding proteins, C
      type lectins, scavenger receptors, galectins, fibrinogen-related proteins,
      thioester-containing protein, Down syndrome cell adhesion molecule, serine
      protease homologs, trans-activation response RNA-binding protein and Toll like
      receptors. A number of PRRs have been functionally studied and have been found to
      have different binding specificities and immune functions. The present review
      aims to summarize the current knowledge on the PRRs of shrimp.

PMID- 22960102
TI  - A chemical approach for the mitigation of Prymnesium parvum blooms.
AB  - Known as Golden Algae in popular media, the harmful algal bloom causing organism
      Prymnesium parvum secretes increased amounts of toxic chemicals called prymnesins
      when stressed, resulting in major fish kills in Texas. Although many options
      exist for mitigation of blooms, a feasible protocol for control of blooms on
      large-scale impoundments has yet to be identified. Chemical control of P. parvum
      using six different enzyme inhibiting aquatic herbicides was explored in
      laboratory experiments. Of the six chemicals screened, one (flumioxazin) was
      selected for further study due to a significant decrease in P. parvum cell
      numbers with increasing chemical concentration. It was applied to natural
      plankton communities during in-situ experiments (Lake Granbury, Texas). The first
      experiment was conducted during a period of P. parvum bloom initiation (March)
      and the second experiment conducted during a post bloom period (April).
      Experiments were carried out in 20 L polycarbonate carboys covered in 30% shade
      cloth to simulate natural light, temperature and turbulence conditions. Through
      cell counts via light-microscopy, the chemical flumioxazin was found to cause
      significant decreases in P. parvum, but no significant differences in zooplankton
      abundance during the period of bloom initiation. However, significant decreases
      in adult copepods were observed during the post bloom period, with no significant
      decreases in P. parvum most likely due to decreased light penetration and
      inhibition of the photosensitive mode of action.

PMID- 22960104
TI  - Coumarins from Angelica archangelica Linn. and their effects on anxiety-like
      behavior.
AB  - TRADITIONAL RELEVANCE: Angelica archangelica Linn. (Apiaceae) is an herb
      distributed in tropical and subtropical regions of the world. Both in Chinese and
      Indian system of medicine, it is used for nervous disorders including anxiety,
      anorexia, migraine and other cerebral diseases. AIM OF STUDY: To evaluate the
      anxiolytic potential of non polar coumarins isolated from A. archangelica Linn.
      METHODS AND RESULTS: A. archangelica Linn. (1 kg) was subjected to extraction in
      a soxhlet apparatus with petroleum ether (40-60  degrees C), yield 6.9% w/w. The
      extract of petroleum ether produced a yellow colored precipitate (YP) which was
      evaluated for anxiolytic like effect using EPM test and was found significant
      (**P<0.01) in doses of 5 and 10 mg/kg, po. The precipitate was shown to be a
      mixture of seven constituents in HPTLC and six on the TLC plate which were
      further subjected to separation by preparative TLC. Non polar coumarins were
      isolated namely imperatorin (IM) and isoimperatorin (IIM). YP, IM, IIM were
      tested for anxiolytic like effects in a dose of 5mg/kg, po along with DZ (1mg/kg,
      po) using EPM, Light & dark arena and hole board models in rats. All the test
      drugs were found to have significant (*P<0.05, **P<0.01) activity. IM and IIM
      have the potential to reduce anxiety but yellow precipitate showed the most
      promising activity as compared to isolated coumarins. This effect may be due to
      the synergistic action of all compounds present in the YP or by multiple
      mechanism of action. The test drugs may have the potential for different
      receptors. CONCLUSION: The mixture of coumarins isolated from A. archangelica and
      its constituents imperatorin and isoimperatorin have the potential to reduce
      anxiety but it is the mixture which have more significant activity as compared to
      its individual components.

PMID- 22960103
TI  - Ghrelin and eating disorders.
AB  - There is growing evidence supporting a multifactorial etiology that includes
      genetic, neurochemical, and physiological components for eating disorders above
      and beyond the more conventional theories based on psychological and
      sociocultural factors. Ghrelin is one of the key gut signals associated with
      appetite, and the only known circulating hormone that triggers a positive energy
      balance by stimulating food intake. This review summarizes recent findings and
      several conflicting reports on ghrelin in eating disorders. Understanding these
      findings and inconsistencies may help in developing new methods to prevent and
      treat patients with these disorders.

PMID- 22960106
TI  - Defects in neuromuscular junction remodelling in the Smn(2B/-) mouse model of
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease
      caused by mutations and deletions within the survival motor neuron 1 (SMN1) gene.
      Although other tissues may be involved, motor neurons remain primary pathological
      targets, with loss of neuromuscular junctions (NMJs) representing an early and
      significant event in pathogenesis. Although defects in axonal outgrowth and
      pathfinding have been observed in cell culture and in lower organisms upon Smn
      depletion, developmental defects in mouse models have been less obvious. Here, we
      have employed the Smn(2B/-) mouse model to investigate NMJ remodelling during SMA
      pathology, induced reinnervation, and paralysis. We show that whilst NMJs are
      capable of remodelling during pathogenesis, there is a marked reduction in
      paralysis-induced remodelling and in the nerve-directed re-organisation of
      acetylcholine receptors. This reduction in remodelling potential could not be
      attributed to a decreased rate of axonal growth. Finally, we have identified a
      loss of terminal Schwann cells which could contribute to the defects in
      remodelling/maintenance observed. Our work demonstrates that there are specific
      defects in NMJ remodelling in an intermediate SMA mouse model, which could
      contribute to or underlie pathogenesis in SMA. The development of strategies that
      can promote the remodelling potential of NMJs may therefore be of significant
      benefit to SMA patients. 

PMID- 22960105
TI  - Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice.
AB  - Focal brain ischemia in adult rats rapidly and robustly induces neurogenesis in
      the subventricular zone (SVZ) but there are few and inconsistent reports in mice,
      presenting a hurdle to genetically investigate the endogenous neurogenic
      regulators such as ciliary neurotrophic factor (CNTF). Here, we first provide a
      platform for further studies by showing that middle cerebral artery occlusion in
      adult male C57BL/6 mice robustly enhances neurogenesis in the SVZ only under very
      specific conditions, i.e., 14days after a 30min occlusion. CNTF expression
      paralleled changes in the number of proliferated, BrdU-positive, SVZ cells.
      Stroke-induced proliferation was absent in CNTF-/- mice, suggesting that it is
      mediated by CNTF. MCAO-increased CNTF appears to act on C cell proliferation and
      by inducing FGF2 expression but not via EGF expression or Notch1 signaling of
      neural stem cells in the SVZ. CNTF is unique, as expression of other gp130
      ligands, IL-6 and LIF, did not predict SVZ proliferation or showed no or only
      small compensatory increases in CNTF-/- mice. Expression of tumor necrosis factor
      alpha, which can inhibit neurogenesis, and the presence of leukocytes in the SVZ
      were inversely correlated with neurogenesis, but pro-inflammatory cytokines did
      not affect CNTF expression in cultured astrocytes. These results suggest that
      slowly up-regulated CNTF in the SVZ mediates stroke-induced neurogenesis and is
      counteracted by inflammation. Further pharmacological stimulation of endogenous
      CNTF might be a good therapeutic strategy for cell replacement after stroke as
      CNTF regulates normal patterns of neurogenesis and is expressed almost
      exclusively in the nervous system. 

PMID- 22960107
TI  - Adenosine-triphosphate-sensitive K+ channel (Kir6.1): a novel phosphospecific
      interaction partner of connexin 43 (Cx43).
AB  - Connexin 43 (Cx43) is a phosphoprotein expressed in a wide variety of cells. Cx43
      and adenosine-triphosphate-sensitive K(+)channels [K(+)(ATP)] are part of same
      signaling pathway that regulates cell survival during stress and ischemia
      preconditioning. Molecular mechanism for their coordinated role in
      ischemia/hypoxia preconditioning is not well known. Using pull down, co
      immunoprecipitation assays and co-localization studies we provide evidence, for
      the first time that Kir6.1, a K(+)(ATP) channel protein component, can interact
      with Cx43. Further we show that the interaction was phospho-specific such that
      Cx43 phosphorylated at serine 262 (S262) interacted with Kir6.1 in preference to
      the unphosphorylated form of Cx43. Introduction of phospho-deficient mutation at
      serine 262 (S262A) in Cx43 completely abolished the interaction. Our data provide
      an interesting lead about a possible partnership between Cx43 and Kir6.1, which
      will help in better understanding their role in ischemia/hypoxia preconditioning.

PMID- 22960108
TI  - The roles and therapeutic potentials of Ephs and ephrins in lung cancer.
AB  - Eph receptors and their membrane-bound ephrin ligands are intimately involved in
      embryonic patterning, neuronal targeting, and vascular development during normal
      embryogenesis. In recent years, a growing number of studies revealed their
      participation in the development of various cancers. In this review, we
      concentrate on their involvement in lung cancer. In this context, we summarize
      their aberrant expressions, their pro- or anti-oncogenic effects as well as
      related mechanisms, and their potential as drug targets in lung cancer.

PMID- 22960109
TI  - Characterization of coal fly ash nanoparticles and induced oxidative DNA damage
      in human peripheral blood mononuclear cells.
AB  - The nano-sized particles present in coal fly ash (CFA) were characterized through
      the X-ray diffraction (XRD), transmission and scanning electron microscopy (TEM,
      SEM), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy
      (FTIR) analyses. The XRD data revealed the average crystallite size of the CFA
      nanoparticles (CFA-NPs) as 14 nm. TEM and SEM imaging demonstrated predominantly
      spherical and some polymorphic structures in the size range of 11 to 25 nm. The
      amount of heavy metal associated with CFA particles (MUg/g) were determined as Fe
      (34160.0+/-1.38), Ni (150.8+/-0.78), Cu (99.3+/-0.56) and Cr (64.0+/-0.86).
      However, the bioavailability of heavy metals in terms of percent release was in
      the order as Cr>Ni>Cu>Fe in CFA-dimethyl sulfoxide (DMSO) extract. The comet and
      cytokinesis blocked micronucleus (CBMN) assays revealed substantial genomic DNA
      damage in peripheral blood mononuclear (PBMN) cells treated with CFA-NPs in Aq
      and DMSO extracts. About 1.8 and 3.6 strand breaks per unit of DNA were estimated
      through alkaline unwinding assay at 1:100 DNA nucleotide/CFA ppm ratios with the
      Aq and DMSO extracts, respectively. The DNA and mitochondrial damage was
      invariably greater with CFA-DMSO extract vis-a-vis -Aq extract. Generation of
      superoxide anions (O(2)*(-)) and intracellular reactive oxygen species (ROS)
      through metal redox-cycling, alteration in mitochondrial potential and 8-oxodG
      production elucidated CFA-NPs induced oxidative stress as a plausible mechanism
      for CFA-induced genotoxicity.

PMID- 22960110
TI  - Seasonal differences of the atmospheric particle size distribution in a
      metropolitan area in Japan.
AB  - We compared the effect of ambient temperature observed in two different seasons
      on the size distribution and particle number concentration (PNC) as a function of
      distance (up to ~250 m) from a major traffic road (25% of the vehicles are heavy
      duty diesel vehicles). The modal particle diameter was found between 10 and 30 nm
      at the roadside in the winter. However, there was no peak for this size range in
      the summer, even at the roadside. Ambient temperature affects both the
      atmospheric dilution ratio (DR) and the evaporation rate of particles, thus it
      affects the decay rate of PNC. We corrected the DR effect in order to focus on
      the effect of particle evaporation on PNC decay. The decay rate of PNC with DR
      was found to depend on the season and particle diameter. During the winter, the
      decay rate for smaller particles (<30 nm) was much higher (i.e., the
      concentration decreased significantly against DR), whereas it was low during the
      summer. In contrast, for particles >30 nm in diameter, the decay rate was nearly
      the same during both seasons. This distinction between particles less than or
      greater than 30 nm in diameter reflects differences in particle volatility
      properties. Mass-transfer theory was used to estimate evaporation rates of C20
      C36 n-alkane particles, which are the major n-alkanes in diesel exhaust
      particles. The C20-C28 n-alkanes of 30-nm particles completely evaporate at 31.2 
      degrees C (summer), and their lifetime is shorter than the transport time of air
      masses in our region of interest. Absence of the peak at 10-30 nm and the low
      decay rate of PNC <30 nm in diameter in the summer were likely due to the
      evaporation of compounds of similar volatilities comparable to the C20-C36 n
      alkanes from particles near the exhaust pipes of vehicles, and complete
      evaporation of semivolatile materials before they reached the roadside. These
      results suggest that the lifetime of particles <30 nm in diameter depends on the
      ambient temperature, which differs between seasons. This leads us to conclude
      that these particles show distinctly different spatial distributions depending on
      the season.

PMID- 22960111
TI  - The significance of hazardous chemicals in wastewater treatment works effluents.
AB  - The advent of increasingly stringent and wider ranging European Union legislation
      relating to water and the environment has required regulators to assess
      compliance risk and to respond by formulating appropriate pollution control
      measures. To support this process the UK Water Industry has completed a national
      Chemicals Investigation Programme (CIP), to monitor over 160 wastewater treatment
      works (WwTWs) for 70 determinands. Final effluent concentrations of zinc,
      polynuclear aromatic hydrocarbons (fluoranthene, benzo(a)pyrene,
      benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(g,h,i)perylene and indeno(1,2,3
      cd)pyrene), "penta" congeners (BDEs) 47 and 99, tributyltin, triclosan,
      erythromycin, oxytetracycline, ibuprofen, propranolol, fluoxetine, diclofenac,
      17beta-estradiol and 17alpha-ethinyl estradiol exceeded existing or proposed
      Environmental Quality Standards (EQSs) in over 50% of WwTWs. Dilution by
      receiving water might ensure compliance with EQSs for these chemicals, apart from
      the BDEs. However, in some cases there will be insufficient dilution to ensure
      compliance and additional management options may be required.

PMID- 22960112
TI  - Evaluation of historical beryllium abundance in soils, airborne particulates and
      facilities at Lawrence Livermore National Laboratory.
AB  - Beryllium has been historically machined, handled and stored in facilities at
      Lawrence Livermore National Laboratory (LLNL) since the 1950s. Additionally,
      outdoor testing of beryllium-containing components has been performed at LLNL's
      Site 300 facility. Beryllium levels in local soils and atmospheric particulates
      have been measured over three decades and are comparable to those found elsewhere
      in the natural environment. While localized areas of beryllium contamination have
      been identified, laboratory operations do not appear to have increased the
      concentration of beryllium in local air or water. Variation in airborne beryllium
      correlates to local weather patterns, PM10 levels, normal sources (such as
      resuspension of soil and emissions from coal power stations) but not to LLNL
      activities. Regional and national atmospheric beryllium levels have decreased
      since the implementation of the EPA's 1990 Clean-Air-Act. Multi-element analysis
      of local soil and air samples allowed for the determination of comparative ratios
      for beryllium with over 50 other metals to distinguish between natural beryllium
      and process-induced contamination. Ten comparative elemental markers (Al, Cs, Eu,
      Gd, La, Nd, Pr, Sm, Th and Tl) that were selected to ensure background variations
      in other metals did not collectively interfere with the determination of
      beryllium sources in work-place samples at LLNL. Multi-element analysis and
      comparative evaluation are recommended for all workplace and environmental
      samples suspected of beryllium contamination. The multi-element analyses of soils
      and surface dusts were helpful in differentiating between beryllium of
      environmental origin and beryllium from laboratory operations. Some surfaces can
      act as "sinks" for particulate matter, including carpet, which retains entrained
      insoluble material even after liquid based cleaning. At LLNL, most facility
      carpets had beryllium concentrations at or below the upper tolerance limit
      determined by sampling facilities with no history of beryllium work. Some
      facility carpets had beryllium concentrations above the upper tolerance limits
      but can be attributed to tracking of local soils, while other facilities showed
      process-induced contamination from adjacent operations. In selected cases,
      distinctions were made as to the source of beryllium in carpets. Guidance on the
      determination of facility beryllium sources is given.

PMID- 22960113
TI  - A biokinetic study of 209Po in man.
AB  - Five adult volunteers participated in a biokinetic study of radioactive polonium.
      Portions of about 10 Bq of (209)Po were orally administrated to four of the
      volunteers in a single ingestion. The fifth volunteer ingested a daily amount of
      53 mBq of 209Po for 243 d to study the time to achieve equilibrium between intake
      and excretion for protracted intakes. For the subjects ingesting single intakes
      of (209)Po complete sampling of urine and feces was subsequently collected the
      first few days upon the ingestion. The samples were processed with radiochemical
      extraction and analyzed with alpha spectrometry. In the study, the maximum daily
      excretion rates in feces were 18-50% of the ingested activity, observed within 3
      d after intake. Regarding the urine excretion, the daily excretion peaked, on
      average, at 0.15-1% of the ingested activity within two days upon intake. These
      results indicate an average gastro-intestinal uptake fraction of 0.46+/-0.08,
      which agrees well with earlier biokinetic studies of polonium in man.

PMID- 22960114
TI  - Stabilin-1 expression in tumor associated macrophages.
AB  - Glioblastoma multiforme is a very aggressive and common form of brain tumor.
      Current therapies consist of a combination of surgical removal, chemotherapy and
      radiation therapy. These drastic treatments still leave a current prognosis of
      median survival of less than 1 year. Lack of effectiveness of these treatments
      has left researchers looking for alternative forms of treatment. A significant
      alternative currently being investigated is the use of the immune system to
      potentially target and eliminate tumor cells directly. Stabilin-1, a scavenger
      receptor expressed by macrophages, has the potential in inhibiting tumor growth
      by binding and internalizing secreted protein acidic and rich in cysteine
      (SPARC). SPARC is known to be upregulated in the tumor microenvironment and is
      involved in extracellular matrix remodeling, cell proliferation and migration.
      Decreasing SPARC expression using siRNA has been shown to decrease tumor
      invasiveness and survival. We investigated the phenotype of stabilin-1 expressing
      immune cells in the tumor environment and demonstrated a transient population of
      alternatively activated macrophages expressing stabilin-1 in the tumor
      environment and the disappearance of that population as the tumor progresses.

PMID- 22960115
TI  - A combination of taxol infusion and human umbilical cord mesenchymal stem cells
      transplantation for the treatment of rat spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Studies have shown that the administration of Taxol, an
      anti-cancer drug, inhibited scar formation, promoted axonal elongation and
      improved locomotor recovery in rats after spinal cord injury (SCI). We
      hypothesized that combining Taxol with another promising therapy, transplantation
      of human umbilical mesenchymal stem cells (hUCMSCs), might further improve the
      degree of locomotor recovery. The present study examined whether Taxol combined
      with transplantation of hUCMSCs would produce synergistic effects on recovery and
      which mechanisms were involved in the effect. METHODS: A total of 32 rats
      subjected to SCI procedures were assigned to one of the following four treatment
      groups: phosphate-buffered saline (PBS, control), hUCMSCs, Taxol, or
      Taxol+hUCMSCs. Immediately after injury, hUCMSCs were transplanted into the
      injury site and Taxol was administered intrathecally for 4 weeks. Locomotor
      recovery was evaluated using the Basso, Beattie and Bresnahan locomotor (BBB)
      rating scale. Survival of the transplanted human cells and the host glial
      reaction in the injured spinal cord were studied by immunohistochemistry.
      RESULTS: Treatment with Taxol, hUCMSCs or Taxol+hUCMSCs reduced the extent of
      astrocytic activation, increased axonal preservation and decreased the number of
      caspase-3(+) and ED-1(+) cells, but these effects were more pronounced in the
      Taxol+hUCMSCs group. Behavioral analyses showed that rats in the Taxol+hUCMSCs
      group showed better motor performance than rats treated with hUCMSCs or Taxol
      only. CONCLUSIONS: The combination of Taxol and hUCMSCs produced beneficial
      effects in rats with regard to functional recovery following SCI through the
      enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal
      preservation effects.

PMID- 22960116
TI  - Proactive and reactive control during emotional interference and its relationship
      to trait anxiety.
AB  - In classic Stroop paradigms, increasing the proportion of control-demanding
      incongruent trials results in strategic adjustments in behavior and
      implementation of cognitive control processes. We manipulated expectancy for
      incongruent trials in an emotional facial Stroop task to investigate the
      behavioral and neural effects of proportion manipulation in a cognitively
      demanding task with emotional stimuli. Subjects performed a high expectancy (HE)
      task (65% incongruent trials) and a low expectancy (LE) task (35% incongruent
      trials) during functional magnetic resonance imaging (fMRI). As in standard
      Stroop tasks, behavioral interference was reduced in the emotional facial Stroop
      HE task compared to the LE task. Functional MRI data revealed a switch in
      cognitive control strategy, from a reactive, event-related activation of a medial
      and lateral cognitive control network and right amygdala in the LE task to a
      proactive, sustained activation of right dorsolateral prefrontal cortex (DLPFC)
      in the HE task. Higher trait anxiety was associated with impairment (slower
      response time and decreased accuracy) as well as reduced activity in left
      ventrolateral prefrontal cortex, anterior insula, and orbitofrontal cortex in the
      HE task on high conflict trials with task-irrelevant emotional information,
      suggesting that individual differences in anxiety may be associated with
      expectancy-related strategic control adjustments, particularly when emotional
      stimuli must be ignored.

PMID- 22960118
TI  - Connexin 36 promotes cortical spreading depolarization and ischemic brain damage.
AB  - Cortical spreading depolarization (CSD) promotes the progression of neuronal
      injury after cerebral ischemia. However, the mechanisms of propagation of
      postischemic CSD events are still unclear. In this study we characterized the
      role of the main neuronal gap junction protein connexin 36 (Cx36) in generating
      postischemic CSDs. In Cx36-deficient mice and controls we occluded the distal
      middle cerebral artery. To detect CSD events we recorded the direct current and
      laser Doppler flow. In addition, locomotor function and the infarct size were
      determined. Cx36-deficient mice had significantly fewer and shorter CSD events
      than wild-type controls. Additionally, Cx36 deletion is neuroprotective, leading
      to a better functional outcome and decreased infarct size after ischemia. These
      results suggest a detrimental role for Cx36 after ischemia, possibly by promoting
      CSD.

PMID- 22960117
TI  - Region- and sex-specific changes in CART mRNA in rat hypothalamic nuclei induced
      by forced swim stress.
AB  - Cocaine and amphetamine regulated transcript (CART) mRNA and peptides are highly
      expressed in the paraventricular (PVN), dorsomedial (DMH) and arcuate (ARC)
      nuclei of the hypothalamus. It has been suggested that these nuclei regulate the
      hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system activity, and
      feeding behavior. Our previous studies showed that forced swim stress augmented
      CART peptide expression significantly in whole hypothalamus of male rats. In
      another study, forced swim stress increased the number of CART-immunoreactive
      cells in female PVN, whereas no effect was observed in male PVN or in the ARC
      nucleus of either sex. In the present study, we evaluated the effect of forced
      swim stress on CART mRNA expression in PVN, DMH and ARC nuclei in both male and
      female rats. Twelve male (stressed and controls, n=6 each) and 12 female
      (stressed and controls, n=6 each) Sprague-Dawley rats were used. Control animals
      were only handled, whereas forced swim stress procedure was applied to the
      stressed groups. Brains were dissected and brain sections containing PVN, DMH and
      ARC nuclei were prepared. CART mRNA levels were determined by in situ
      hybridization. In male rats, forced swim stress upregulated CART mRNA expression
      in DMH and downregulated it in the ARC. In female rats, forced swim stress
      increased CART mRNA expression in PVN and DMH, whereas a decrease was observed in
      the ARC nucleus. Our results show that forced swim stress elicits region- and sex
      specific changes in CART mRNA expression in rat hypothalamus that may help in
      explaining some of the effects of stress.

PMID- 22960119
TI  - Heterogeneous electrophysiological and morphological properties of neurons in the
      mouse medial amygdala in vitro.
AB  - Neurons in the medial nucleus of the amygdala (MeA) play a key role in the innate
      maternal, reproductive, defensive, and social behaviors. However, it is unclear
      how activation of the vomeronasal system leads to the behavioral outputs that are
      associated with pheromones. Here, we characterized the electrophysiological and
      morphological properties of MeA neurons using whole-cell recordings in mice slice
      preparations. Biocytin labeling revealed that MeA neurons possessed bipolar to
      multipolar cell bodies and dendritic fields covering projection areas from the
      accessory olfactory bulb. In 70% of recorded MeA neurons, monosynaptic excitatory
      postsynaptic currents (EPSCs) were evoked from the accessory olfactory bulb
      afferent in which the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      component was dominant and was rarely followed by the N-methyl-d-aspartic acid
      component. Norepinephrine increased the frequency of spontaneous inhibitory
      postsynaptic currents in some neurons, whereas alpha-methyl-5-hydroxytryptamine
      increased spontaneous EPSCs in other neurons. Morphologically and
      physiologically, heterogeneous MeA neurons appear likely to produce multiplex
      outputs of instinctive behaviors.

PMID- 22960120
TI  - Venous bullet embolism and subsequent endovascular retrieval - A case report and
      review of the literature.
AB  - INTRODUCTION: Vascular bullet embolism is a rare phenomenon with fewer than 200
      cases reported in the literature. PRESENTATION OF CASE: A 22 year-old male
      presented with a gunshot wound to the right lower quadrant. Imaging demonstrated
      a bullet lodged in his left lower quadrant. Upon operative exploration, a single
      hole was found in the right external iliac vein without injury into the left
      lower quadrant. The bullet was found to have migrated intravascularly from the
      right external to the left common iliac vein, and was subsequently removed
      endovascularly. DISCUSSION: Bullet embolism occurs infrequently, with arterial
      more common than venous. Arterial embolization usually requires emergency
      operative intervention due to ischemia. While venous embolization is often
      asymptomatic, removal of the bullet is recommended to avoid delayed complications
      when possible. CONCLUSION: Venous bullet emboli should be removed endovascularly
      whenever technically possible.

PMID- 22960121
TI  - Effect of hemicellulase addition during enzymatic hydrolysis of switchgrass
      pretreated by soaking in aqueous ammonia.
AB  - The focus of this study was to determine the effect of supplementing cellulase
      with hemicellulase during enzymatic hydrolysis of switchgrass pretreated by
      soaking in aqueous ammonia (SAA) under a range of conditions. SAA was performed
      using 15% aqueous ammonia for 8 or 24h at temperatures of 40 or 60 degrees C. The
      combined effect of cellulase and hemicellulase loadings on glucose yield during
      enzymatic hydrolysis was modeled for each pretreatment condition. Glucose yields
      greater than 85% of theoretical were achieved for pretreatment at 40 degrees C
      for 24h and for 60 degrees C for 8h. Hemicellulase supplementation was not
      sufficient to achieve these glucose yields at lower severity SAA pretreatment.
      High severity SAA pretreatment also led to low yields despite improved
      delignification.

PMID- 22960122
TI  - Fatty acid rich effluent from acidogenic biohydrogen reactor as substrate for
      lipid accumulation in heterotrophic microalgae with simultaneous treatment.
AB  - Acid-rich effluent generated from acidogenic biohydrogen production process was
      evaluated as substrate for lipid synthesis by integrating with heterotrophic
      cultivation of mixed microalgae. Experiments were performed both with synthetic
      volatile fatty acids (SVFA) and fermented fatty acids (FFA) from biohydrogen
      producing reactor. Fatty acid based platform evidenced significant influence on
      algal growth as well as lipid accumulation by the formation of triglycerides
      through fatty acid synthesis. Comparatively FFA documented higher biomass and
      lipid productivity (1.42mg/ml (wet weight); 26.4%) than SVFAs ((HAc+HBu+HPr),
      0.60mg/ml; 23.1%). Lipid profiles varied with substrates and depicted 18 types of
      saturated and unsaturated fatty acids with wide fuel and food characteristics.
      The observed higher concentrations of Chl b over Chl a supports the biosynthesis
      of triacylglycerides. Microalgae diversity visualized the presence of lipid
      accumulating species viz., Scenedesmus sp. and Chlorella sp. Integration of
      microalgae cultivation with biohydrogen production showed lipid productivity for
      biodiesel production along with additional treatment.

PMID- 22960123
TI  - Enhanced enzymatic hydrolysis of rice straw by removal of phenolic compounds
      using a novel laccase from yeast Yarrowia lipolytica.
AB  - An extracellular laccase-producing yeast was isolated from soil and identified as
      Yarrowia lipolytica by its morphology and by comparison of its internal
      transcribed spacer rDNA gene sequence. Extracellular laccase (YlLac) from Y.
      lipolytica was purified to homogeneity by anion-exchange and gel filtration
      chromatography. YlLac is a monomeric glycoprotein with 14% carbohydrate content
      and a molecular mass of 67kDa. It showed a higher catalytic efficiency towards
      2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (k(cat)/K(m)=19.3s(-1)MUM(
      1)) and 2,6-dimethoxyphenol (k(cat)/K(m)=13s(-1)MUM(-1)) than any other reported
      laccase. This enzyme was able to oxidize phenolic compounds present in pretreated
      rice straw. Several parameters (temperature, enzyme concentration, and mediator
      compounds) to enhance removal of phenolic compounds from pretreated rice straw
      were optimized using response surface methodology. The use of YlLac for the
      removal of cellulase inhibitory compounds from biomass slurries was found to be a
      promising approach for improving the efficiency of biorefineries.

PMID- 22960124
TI  - Thermogravimetric investigation of hydrochar-lignite co-combustion.
AB  - Co-combustion of hydrochar with lignite was investigated by means of
      thermogravimetric analysis. Hydrochars were produced from coconut fibers and
      eucalyptus leaves under hydrothermal conditions at 250 degrees C. The hydrochar
      was added in varying amounts to lignite for combustion. The results indicated
      that hydrothermal treatment decreased the volatile matter content and increased
      the fixed carbon content of the biomaterials. The elevated energy density and
      decreased ash content of the hydrochar improved its combustion behavior when co
      fired with lignite for energy production. The hydrochars derived from coconut
      fiber and eucalyptus leaves had similar chemical compositions and showed similar
      influences on lignite combustion. Hydrochar addition increased the burnout and
      shortened the combustion range of the hydrochar-lignite blends. High combustion
      efficiency was observed due to the synergistic interactions between hydrochar and
      lignite during the co-combustion process. A kinetic study showed that the
      combustion process of hydrochar-lignite blends followed first-order reaction
      rates.

PMID- 22960125
TI  - Mtl1 O-mannosylation mediated by both Pmt1 and Pmt2 is important for cell
      survival under oxidative conditions and TOR blockade.
AB  - Mtl1 is a cell surface sensor and member of the Pkc1-MAPK pathway that senses
      oxidative stress and nutrient starvation. Here we demonstrate that the Mtl1
      cytoplasmic domain physically interacts with the GEF (GTPase Exchange Factor)
      protein Rom2 of the CWI (Cell wall Integrity) pathway. Mtl1 is N-glycosylated
      protein, highly O-mannosylated by Pmt1, Pmt4 and mostly by Pmt2. Mtl1 localises
      to the bud, septum, the tip of the shmoo and the cell periphery. The O
      mannosylation deficiency that occurs in both the pmt1 and pmt2 mutants adversely
      affects the distribution of Mtl1 on the septum and also hinders Mtl1 localisation
      in the tip of the shmoo. Here we present results demonstrating that: (i) O
      mannosylation and, more specifically that affecting Mtl1 protein is required for
      cell survival in response to both oxidative stress and TOR blockade; (ii) Slt2
      activity is impaired upon rapamycin treatment in both pmt2 and mtl1 mutants;
      (iii) Mtl1 is transcriptionally upregulated in quiescent conditions, (iv) O
      mannosylation mediated by Pmt1 and Pmt2 favours Mtl1 protein stability. We
      propose a relevant role for Mtl1 O-mannosylation mediated by both Pmt1 and Pmt2
      in the response to oxidative stress and in rapamycin treatment.

PMID- 22960126
TI  - Effect of heterozygous beta thalassemia on the phosphorylative response to
      Plasmodium falciparum infection.
AB  - Malaria parasites interact with the host cell membrane inserting new proteins and
      inducing oxidative and phosphorylative changes of erythrocyte proteins. In the
      present report we monitored the time dependent oxidative and phosphorylative
      modifications induced by parasites in heterozygous beta thalassemia (Het
      betaThal). Het-betaThal causes mild anemia and is known to determine a pro
      oxidant milieu and a protective effect against severe malaria. In malaria
      cultures Het-betaThal has been reported to induce accumulation of hemoglobin
      denaturation products. At early parasite development stages (rings), tyrosine
      hyper-phosphorylation of band 3 was the most notable modification, and at later
      development stages (trophozoites), additional membrane proteins displayed
      significant hyper-phosphorylation of their serine and tyrosine residues
      (adducins, ankyrin, catalase). Het-betaThal also caused membrane destabilization.
      Free radical scavengers effectively inhibited the phosphorylative response and
      membrane destabilization. Kinase inhibitors exerted similar effects suggesting a
      causal relationship between oxidative stress, membrane protein hyper
      phosphorylation and increased membrane damage exacerbated by Het-betaThal. In
      conclusion, different lines of evidence suggest that Het-betaThal enhances the
      redox stress caused by malaria parasites inducing its protective effect
      destabilizing the host cell membrane. This article is part of a Special Issue
      entitled: Integrated omics.

PMID- 22960127
TI  - Fluoxetine reverses depressive-like behaviors and increases hippocampal
      acetylcholinesterase activity induced by olfactory bulbectomy.
AB  - The olfactory bulbectomy (OB) is an animal model of depression that results in
      behavioral, neurochemical and neuroendocrinological changes, features comparable
      to those seen in depressive patients. This study investigated OB-induced
      alterations in locomotor activity and exploratory behavior in the open-field
      test, self-care and motivational behavior in the splash test, hyperactivity in
      the novel object test and novel cage test, and the influence of chronic treatment
      with fluoxetine (10mg/kg, p.o., once daily for 14days) on these parameters.
      Fluoxetine reversed OB-induced hyperactivity in the open-field test, locomotor
      hyperactivity and the increase in exploratory behavior induced by novelty in the
      novel object and novel cage tests, and the loss of self-care and motivational
      behavior in the splash test. Moreover, OB decreased the number of grooming and
      fecal boli in the open-field and novel cage tests, alterations that were not
      reversed by fluoxetine. OB caused an increase in hippocampal, but not in
      prefrontal acetylcholinesterase (AChE) activity. Fluoxetine was able to reverse
      the increase in hippocampal AChE activity induced by OB. Serum corticosterone was
      increased in SHAM and bulbectomized mice treated with fluoxetine. In conclusion,
      OB mice exhibited depressive-like behaviors associated with an increase in
      hippocampal AChE activity, effects that were reversed by chronic treatment with
      fluoxetine.

PMID- 22960128
TI  - Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant
      like effect of ferulic acid in the tail suspension test.
AB  - Ferulic acid (FA, 4-hydroxy-3-methoxycinnamic acid) is a phytochemical compound
      naturally present in several plants and foods that is approved as an antioxidant
      additive and food preservative. It exerts a beneficial action in chronic mild
      stress-induced depressive-like behavior and produces an acute antidepressant-like
      effect in the tail suspension test (TST) through the activation of the
      serotonergic system. This study was aimed at investigating the possible
      involvement of signaling pathways in the antidepressant-like effect of acute and
      oral administration of FA, in the TST in mice. The anti-immobility effect of
      orally administered FA (0.01mg/kg, p.o.) was prevented by pretreatment of mice
      with H-89 (1MUg/site, i.c.v., an inhibitor of PKA), KN-62 (1MUg/site, i.c.v., an
      inhibitor of CaMKII), GF109203X (5ng/site, i.c.v., an inhibitor of PKC), U0126
      (5MUg/site, i.c.v., an inhibitor of MAPK/ERK) or LY294002 (10nmol/site, i.c.v.,
      an inhibitor of PI3K), all involved with neurotrophic signaling pathways. The
      results demonstrated that FA exerts antidepressant-like effect in the TST in
      mice, through the activation of signaling pathways related to neuroplasticity,
      neurogenesis and cell survival.

PMID- 22960129
TI  - Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous
      convulsions in lithium-pilocarpine induced status epilepticus in rat model.
AB  - Accumulating evidence has shown that neuroinflammation plays a key role in
      epileptogenesis. However, the efficacy of anti-inflammatory agents for preventing
      epilepsy remains controversial. Fingolimod (FTY720), a sphingosine-1-phosphate
      (S1P) analog, has potent anti-inflammatory effects in multiple sclerosis (MS)
      patients and animal models. Here, we tested whether FTY720 could exert
      antiepileptogenic effects in an adult rat model of lithium-pilocarpine induced
      epilepsy. 24h after onset of status epilepticus (SE), the epileptic rats received
      saline or 1mg/kg FTY720 i.p. once daily for 14 consecutive days. Thereafter,
      spontaneous convulsions (SCs), mossy fiber sprouting (MFS), neuronal loss,
      activation of microglia and astrocytes, expressions of interleukin-1 beta (IL
      1beta) and tumor necrosis factor alpha (TNFalpha) were evaluated in the SE rats.
      We found that FTY720 treatment reduced neuronal loss and decreased activation of
      microglia and astrocytes in hippocampus at four days post-SE. Simultaneously,
      abnormal expressions of IL-1beta and TNFalpha in hippocampus were restrained by
      FTY720 treatment. In addition, neuroprotective effects of FTY720 were
      demonstrated by increasing neuronal nuclei (NeuN)-positive cells and decreasing
      Fluoro-Jade B (FJB)-positive cells in the hippocampus. During 21-34days post-SE,
      the incidence, duration, frequency and severity of SCs significantly decreased in
      FTY720 treated rats compared with saline treated rats. Aberrant MFS was also
      attenuated by FTY720 administration. These results suggest that FTY720 exerts
      anti-inflammatory and antiepileptogenic effects in lithium-pilocarpine model of
      epilepsy and it may provide a new therapeutic approach for prevention of
      epileptogenesis.

PMID- 22960130
TI  - Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal
      behavior as revealed by c-Fos immunoreactivity.
AB  - Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in
      the treatment of schizophrenia. Besides its well-known side effect on weight
      gain, it may also impair human parental behavior. In this study, we took a
      preclinical approach to examine the behavioral effects of olanzapine on rat
      maternal behavior and investigated the associated neural basis using the c-Fos
      immunohistochemistry. On postpartum days 6-8, Sprague-Dawley mother rats were
      given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0mg/kg,
      sc). Maternal behavior was tested 2h later, after which rats were sacrificed and
      brain tissues were collected. Ten brain regions that were either implicated in
      the action of antipsychotic drugs and/or in the regulation of maternal behavior
      were examined for c-Fos immunoreactivity. Acute olanzapine treatment dose
      dependently disrupted various components of maternal behavior (e.g., pup
      retrieval, pup licking, nest building, crouching) and increased c-Fos
      immunoreactivity in the medial prefrontal cortex (mPFC), nucleus accumbens shell
      and core (NAs and NAc), dorsolateral striatum (DLSt), ventral lateral septum
      (LSv), central amygdala (CeA) and ventral tegmental area (VTA), important brain
      areas generally implicated in the incentive motivation and reward processing. In
      contrast, olanzapine treatment did not alter c-Fos in the medial preoptic nucleus
      (MPN), ventral bed nucleus of the stria terminalis (vBST) and medial amygdala
      (MeA), the core brain areas directly involved in the mediation of rat maternal
      behavior. These findings suggest that olanzapine disrupts rat maternal behavior
      primarily by suppressing incentive motivation and reward processing via its
      action on the mesocorticolimbic dopamine systems, other limbic and striatal
      areas, but not by disrupting the core processes involved in the mediation of
      maternal behavior in particular.

PMID- 22960131
TI  - Amino acid residue E543 in JAK2 C618R is a potential therapeutic target for
      myeloproliferative disorders caused by JAK2 C618R mutation.
AB  - Janus kinase 2 (JAK2) is an important mediator of cytokine receptor signaling and
      plays a key role in the hematopoietic and immune responses. The acquired JAK2
      C618R somatic mutation is detected in a subset of myeloproliferative disorders
      (MPDs) patients and presumed to be a biomarker for MPDs. However, how JAK2 C618R
      mutation causes MPDs is still unclear. Our results indicate that the amino acid
      residue E543 in JAK2 C618R is indispensable for its constitutive activation. When
      the glutamic acid at this position was mutated to alanine (E543A) in the JAK2
      C618R, its activity significantly decreased. However when the glutamic acid was
      mutated to the acidic amino acid, aspartic acid, JAK2 C618R activity changed
      little. These results suggest that there is an interaction between the amino acid
      residue R618 and E543, and that this interaction is crucial to sustain the
      constitutive activation of JAK2 C618R. More importantly, the E543 single mutation
      had no effects on the function of wild type JAK2 (WT JAK2). This study suggests
      that the amino acid residue E543 might be a potential target for specific
      inhibitors to treat MPDs caused by the JAK2 C618R mutation.

PMID- 22960133
TI  - Neuroprotective effects of Schisandrin B against transient focal cerebral
      ischemia in Sprague-Dawley rats.
AB  - Fruits of Schisandra have been traditionally used in East Asia for the treatment
      of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia.
      Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus
      Schisandrae, has been shown to produce antioxidant effect on rodent liver and
      heart. In the present study, we investigated the neuroprotective effects of
      Schisandrin B, a constituent drug of the fruit of Schisandra, against focal
      cerebral ischemia in rats. Schisandrin B (10, 30 mg/kg, i.p.) was twice
      administered 30 min before the onset of ischemia and 2h after reperfusion.
      Schisandrin B 10 and 30 mg/kg treated groups showed infarct volumes reduced by
      25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated
      animal treatment abrogated protein expression of TNF-alpha and IL-1beta and
      degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest
      that Schisandrin B treatment provides a neuroprotective effect to rats after
      transient focal cerebral ischemia by inhibiting inflammation and by protecting
      against metalloproteinase degradation.

PMID- 22960132
TI  - Acidic pH promotes oligomerization and membrane insertion of the BclXL apoptotic
      repressor.
AB  - Solution pH is believed to serve as an intricate regulatory switch in the
      induction of apoptosis central to embryonic development and cellular homeostasis.
      Herein, using an array of biophysical techniques, we provide evidence that acidic
      pH promotes the assembly of BclXL apoptotic repressor into a megadalton oligomer
      with a plume-like appearance and harboring structural features characteristic of
      a molten globule. Strikingly, our data reveal that pH tightly modulates not only
      oligomerization but also ligand binding and membrane insertion of BclXL in a
      highly subtle manner. Thus, while oligomerization and the accompanying molten
      globular content of BclXL is least favorable at pH 6, both of these structural
      features become more pronounced under acidic and alkaline conditions. However,
      membrane insertion of BclXL appears to be predominantly favored under acidic
      conditions. In a remarkable contrast, while ligand binding to BclXL optimally
      occurs at pH 6, it is diminished by an order of magnitude at lower and higher pH.
      This reciprocal relationship between BclXL oligomerization and ligand binding
      lends new insights into how pH modulates functional versatility of a key
      apoptotic regulator and strongly argues that the molten globule may serve as an
      intermediate primed for membrane insertion in response to apoptotic cues.

PMID- 22960134
TI  - Anaerobes isolated from bone and joint infections and their susceptibility to
      antibiotics.

PMID- 22960135
TI  - Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission
      tomography in patients with chronic inflammatory bowel disease: a systematic
      review and a meta-analysis.
AB  - OBJECTIVE: To systematically review and meta-analyze published data about the
      diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron
      emission tomography (PET) and PET/computed tomography (PET/CT) in patients with
      chronic inflammatory bowel disease (IBD). METHODS: A comprehensive computer
      literature search of studies published through May 2012 regarding (18)F-FDG-PET
      and PET/CT in patients with IBD was performed. All retrieved studies were
      reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive
      and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of
      (18)F-FDG PET and PET/CT in patients with IBD on a per segment-based analysis
      were calculated. The area under the ROC curve was calculated to measure the
      accuracy of (18)F-FDG PET and PET/CT in patients with IBD. RESULTS: Nineteen
      studies comprising 454 patients with suspected IBD were included in the
      qualitative analysis (systematic review) and discussed. The quantitative analysis
      (meta-analysis) of seven selected studies (including 219 patients with IBD)
      provided the following results on a per segment-based analysis: sensitivity was
      85% [95% confidence interval (95%CI) 81-88%], specificity 87% (95%CI 84-90%), LR+
      6.19 (95%CI: 2.86-13.41), LR- 0.19 (95%CI: 0.10-0.34), and DOR 44.35 (95%CI:
      11.77-167.07). The area under the ROC curve was 0.933. CONCLUSIONS: In patients
      with suspected IBD (18)F-FDG PET and PET/CT demonstrated good sensitivity and
      specificity, being accurate methods in this setting. Nevertheless, the literature
      focusing on the use of PET and PET/CT in IBD remains still limited; thus, further
      large multicenter studies will be necessary to substantiate the diagnostic
      accuracy of these methods in patients with IBD.

PMID- 22960136
TI  - Induction or exacerbation of psoriatic lesions during anti-TNF-alpha therapy for
      inflammatory bowel disease: a systematic literature review based on 222 cases.
AB  - BACKGROUND: Paradoxical cases of psoriatic lesions induced or exacerbated by anti
      tumor necrosis factor (TNF)-alpha therapy have been reported more frequently in
      recent years, but data related to inflammatory bowel disease (IBD) are rare. A
      systematic literature review was performed to provide information about this
      adverse effect in patients with IBD who receive anti-TNF therapy. METHODS:
      Published studies were identified by a search of Medline, Embase, Cochrane,
      SciELO, and LILACS databases. RESULTS: A total of 47 studies (222 patients)
      fulfilled the inclusion criteria and were selected for analysis. Clinical and
      therapeutic aspects varied considerably among these reports. Of the 222 patients,
      78.38% were diagnosed with Crohn's disease, and 48.20% were female. The mean
      patient age was 26.50 years, and 70.72% of patients had no history of psoriasis.
      Patients developed psoriasiform lesions (55.86%) more often than other types of
      psoriatic lesions, and infliximab was the anti-TNF-alpha therapy that caused the
      cutaneous reaction in most patients (69.37%). Complete remission of cutaneous
      lesions was observed in 63.96% of the cases. CONCLUSIONS: We found that psoriatic
      lesions occurred predominantly in adult patients with Crohn's disease who
      received infliximab and had no previous history of psoriasis. Most patients can
      be managed conservatively without discontinuing anti-TNF-alpha therapy.

PMID- 22960137
TI  - Disappointing results following proctectomy with end-colostomy for anorectal
      Crohn's disease.

PMID- 22960138
TI  - Attention is needed for action control: further evidence from grasping.
AB  - In this study we investigated whether motor and perceptual tasks share common
      attentional resources. To this end, we used a dual-task paradigm requiring
      participants to perform grasping movements toward objects of varying size and at
      the same time to identify a perceptual target presented at the object's location.
      To ensure that both tasks were performed simultaneously and to prevent
      participants from adopting a sequential strategy, the perceptual target was
      always presented after movement onset and could occur at two different moments in
      time (early vs. late). Our findings show that both, the planning and the control
      of the movement were altered in the dual-task condition, resulting in prolonged
      reaction times and delayed adjustment of the grip to object size. Also, the
      perceptual performance was impaired when both tasks were performed concurrently.
      These findings are in contrast with previous studies suggesting that only
      movement planning but not movement control are susceptible to dual-task
      interferences (Enns & Liu, 2009, chap. 12). Instead, our results give further
      evidence for the proposition that the dorsal (visuomotor) and ventral
      (perceptual) stream share the same attentional resources and that attention is
      required for effective grasping.

PMID- 22960140
TI  - Neurological picture. Idiopathic hypertrophic cranial pachymeningitis: a rare but
      treatable cause of headache and facial pain.

PMID- 22960141
TI  - Modulation of CYP1A1, CYP1B1 and DNA adducts level by green and white tea in
      Balb/c mice.
AB  - In the current investigation the ameliorative effect of 2% extract of green tea
      (GT) and white tea (WT) against benzo(a)pyrene (BaP) induced toxicity and DNA
      damage has been studied in liver and lung of Balb/c mice (8 animals per group).
      The activities of phase I enzymes such as 7-ethoxyresorufin O-deethylase (EROD)
      and pentoxyresorufin O-depentylase (PROD) were found to be increased (p<0.05)
      both in liver and lung of BaP treated (125 mg/kg b.w. orally) group. The enhanced
      activities of EROD and PROD were inhibited in group that received pretreatment
      with GT and WT for 35 days. Pretreatment with GT and WT also elevated (p<0.05)
      the level of detoxifying enzymes such as glutathione S-transferase (GST) and
      quinone reductase (QR) in both the tissues. The BaPDE-DNA adducts level reflected
      the decreasing pattern from BaP treated group to the groups that received
      pretreatment with GT and WT. BaP exposure induced drastic alterations in the
      morphology of erythrocytes, pretreatment of GT and WT to BaP administered groups
      showed reduced alteration in topography of erythrocytes. WT elucidate greater
      efficacy in ameliorating BaP toxicity, but further long term studies are required
      to validate white tea as a cancer chemopreventive agent.

PMID- 22960142
TI  - Molecular phylogeny of Chloropseidae and Irenidae - cryptic species and
      biogeography.
AB  - Chloropseidae (Leafbirds) and Irenidae (Fairy-bluebirds) are colourful Oriental
      birds, which have been placed as a deep (old) branch in the radiation of
      passeroid songbirds. We present a densely sampled molecular phylogeny of the two
      families based on two nuclear introns (GAPDH and ODC) and two mitochondrial genes
      (ND3 and cyt-b) largely stemming from old museum specimens. Our results show that
      several subspecies within both Chloropseidae and Irenidae are genetically
      distinct and separated in the Miocene some 10-11Million years ago (Mya),
      indicating a substantial underestimation of species numbers within the two
      families. Based on our molecular findings, plumage distinctiveness and
      contemporary distributions we propose that several subspecies be recognised at
      the species level. Furthermore, we use the molecular data to examine
      biogeographical patterns of the two families in the light of historical
      geological re-arrangements in the region. The results indicate that the
      Philippines were colonised in the Pliocene and that colonisation probably
      progressed via the Sulu islands from Borneo and not via Palawan, which was first
      colonised in the Pleistocene.

PMID- 22960143
TI  - Primate molecular phylogenetics in a genomic era.
AB  - A primary objective of molecular phylogenetics is to use molecular data to
      elucidate the evolutionary history of living organisms. Dr. Morris Goodman
      founded the journal Molecular Phylogenetics and Evolution as a forum where
      scientists could further our knowledge about the tree of life, and he recognized
      that the inference of species trees is a first and fundamental step to addressing
      many important evolutionary questions. In particular, Dr. Goodman was interested
      in obtaining a complete picture of the primate species tree in order to provide
      an evolutionary context for the study of human adaptations. A number of recent
      studies use multi-locus datasets to infer well-resolved and well-supported
      primate phylogenetic trees using consensus approaches (e.g., supermatrices). It
      is therefore tempting to assume that we have a complete picture of the primate
      tree, especially above the species level. However, recent theoretical and
      empirical work in the field of molecular phylogenetics demonstrates that
      consensus methods might provide a false sense of support at certain nodes. In
      this brief review we discuss the current state of primate molecular phylogenetics
      and highlight the importance of exploring the use of coalescent-based analyses
      that have the potential to better utilize information contained in multi-locus
      data.

PMID- 22960144
TI  - Historical profiling of maize duplicate genes sheds light on the evolution of C4
      photosynthesis in grasses.
AB  - C4 plants evolved from C3 plants through a series of complex evolutionary steps.
      On the basis of the evolution of key C4 enzyme genes, the evolution of C4
      photosynthesis has been considered a story of gene/genome duplications and
      subsequent modifications of gene function. If whole-genome duplication has
      contributed to the evolution of C4 photosynthesis, other genes should have been
      duplicated together with these C4 genes. However, which genes were co-duplicated
      with C4 genes and whether they have also played a role in C4 evolution are
      largely unknown. In this study, we developed a simple method to characterize the
      historical profile of the paralogs of a gene by tracing back to the most recent
      common ancestor (MRCA) of the gene and its paralog(s) and then counting the
      number of paralogs at each MRCA. We clustered the genes into clusters with
      similar duplication profiles and inferred their functional enrichments. Applying
      our method to maize, a familiar C4 plant, we identified many genes that show
      similar duplication profiles with those of the key C4 enzyme genes and found that
      the functional preferences of the C4 gene clusters are not only similar to those
      identified by an experimental approach in a recent study but also highly
      consistent with the functions required for the C4 photosynthesis evolutionary
      model proposed by S.F. Sage. Some of these genes might have co-evolved with the
      key C4 enzyme genes to increase the strength of C4 photosynthesis. Moreover, our
      results suggested that most key C4 enzyme genes had different origins and have
      undergone a long evolutionary process before the emergence of C4 grasses
      (Andropogoneae), consistent with the conclusion proposed by previous authors.

PMID- 22960139
TI  - The optic nerve: a "mito-window" on mitochondrial neurodegeneration.
AB  - Retinal ganglion cells (RGCs) project their long axons, composing the optic
      nerve, to the brain, transmitting the visual information gathered by the retina,
      ultimately leading to formed vision in the visual cortex. The RGC cellular
      system, representing the anterior part of the visual pathway, is vulnerable to
      mitochondrial dysfunction and optic atrophy is a very frequent feature of
      mitochondrial and neurodegenerative diseases. The start of the molecular era of
      mitochondrial medicine, the year 1988, was marked by the identification of a
      maternally inherited form of optic atrophy, Leber's hereditary optic neuropathy,
      as the first disease due to mitochondrial DNA point mutations. The field of
      mitochondrial medicine has expanded enormously over the last two decades and many
      neurodegenerative diseases are now known to have a primary mitochondrial etiology
      or mitochondrial dysfunction plays a relevant role in their pathogenic mechanism.
      Recent technical advancements in neuro-ophthalmology, such as optical coherence
      tomography, prompted a still ongoing systematic re-investigation of retinal and
      optic nerve involvement in neurodegenerative disorders. In addition to inherited
      optic neuropathies, such as Leber's hereditary optic neuropathy and dominant
      optic atrophy, and in addition to the syndromic mitochondrial encephalomyopathies
      or mitochondrial neurodegenerative disorders such as some spinocerebellar ataxias
      or familial spastic paraparesis and other disorders, we draw attention to the
      involvement of the optic nerve in classic age-related neurodegenerative disorders
      such as Parkinson and Alzheimer disease. We here provide an overview of optic
      nerve pathology in these different clinical settings, and we review the possible
      mechanisms involved in the pathogenesis of optic atrophy. This may be a model of
      general value for the field of neurodegeneration. This article is part of a
      Special Issue entitled 'Mitochondrial function and dysfunction in
      neurodegeneration'.

PMID- 22960145
TI  - Clinical and financial comparison of operative and nonoperative treatment of
      displaced clavicle fractures.
AB  - HYPOTHESIS: Surgical stabilization of displaced clavicle fractures was once
      considered to have rare indications. Our purpose was to present the clinical and
      economic effects of surgical management using data collected from operative and
      nonoperative patients. METHODS: Our fracture database was queried from January 1,
      2005, to January 1, 2010, identifying 204 patients with displaced midclavicular
      fractures. Radiographs and charts were reviewed, and questionnaires were
      distributed. RESULTS: Operative patients had less chronic pain (6.1% vs 25.3%),
      less cosmetic deformity (18.2% vs 32.5%), less weakness (10.6% vs 33.7%), less
      loss of motion (15.2% vs 31.3%), and fewer nonunions (0% vs 4.8%). Operative
      patients missed fewer days of work (8.4 days vs 35.2 days) and required less
      assistance (3 days vs 7 days) for care at home. Mean income lost was $321.69
      versus $10,506.25. Operative patients had a mean emergency department bill of
      $2,060.51 versus $1,871.92 and had a mean hospital bill of $8,520.30 versus
      $3,692.65, and anesthesia charges averaged $946.11. Operative patients required
      less physical therapy, and the mean physical therapy cost was $971.76 versus
      $1,820. Nonoperative patients required more pain medication ($43.22 vs $45.98).
      Overall, the cost was $12,976.94 for operative patients and $18,068.27 for
      nonoperative patients. CONCLUSIONS: Patients with displaced clavicle fractures
      benefit clinically and financially from stabilization. They have less chronic
      pain, less deformity, less weakness, and better range of motion. They return to
      work sooner, take less pain medication, and require less physical therapy. Their
      initial hospital bill is higher because of surgical charges but is balanced by
      less income loss, resulting in a cost savings of $5,091.33 in operative patients.

PMID- 22960146
TI  - The possible role of the transcription factor nuclear factor-kappaB on evolution
      of rotator cuff tear and on mechanisms of cuff tendon healing.
AB  - BACKGROUND: We verified if the nuclear factor-kappaB (NF-kappaB) was present on
      the margins of rotator cuff tears (RCTs). Because NF-kappaB regulates apoptosis
      and stimulates neoangiogenesis, we hypothesized that NF-kappaB has a role in the
      evolution of RCT and in possible mechanisms of RCT healing. MATERIALS AND
      METHODS: Samples from tear margins, subacromial bursa, and healthy subscapular
      tendons were excised during arthroscopic treatment of patients with
      posterosuperior RCT. Sections were cut and stained with hematoxylin and eosin for
      morphologic evaluation and used for immunohistochemical analysis with NF-kappaB
      p65 antibody. RESULTS: The presence of NF-kappaB in the RCT margins and
      subacromial bursa increases with increasing tear size. NF-kappaB is also present
      in the subscapularis tendon of patients with large and massive RCT. Analogously,
      we observed that neoangiogenesis grows with increasing RCT size and is always
      present in the subscapularis tendon independently from RCT size. Statistical
      analysis indicates that NF-kappaB and neoangiogenesis are correlated, regardless
      of the dimension of the RCT. CONCLUSIONS: This is the first study that identifies
      the association between activated NF-kappaB and RCT. Activated NF-kappaB on the
      margins of RCT increases with increasing tear size. We hypothesized a series of
      possible causes responsible for NF-kappaB activation; however, we believe that
      activation is due to tissue hypoxia. Activated p65 directly stimulates
      neoangiogenesis, but the same factors that regulate NF-kappaB activation might
      also act as neoangiogenesis inductors.

PMID- 22960147
TI  - Incidence of early radiolucent lines after glenoid component insertion for total
      shoulder arthroplasty: a radiographic study comparing pressurized and
      unpressurized cementing techniques.
AB  - BACKGROUND: Total shoulder arthroplasty (TSA) is commonly performed for arthritic
      conditions of the shoulder. The outcome after TSA is generally good, but there
      are several modes of failure, with one of the more common reasons being glenoid
      loosening. One possible cause for glenoid loosening is inadequate cementation
      technique. The purpose of this study was to evaluate the incidence of lucent
      lines on the first postoperative radiograph using 2 different cementation
      techniques. MATERIALS AND METHODS: One hundred consecutive patients had a pegged
      glenoid placed with 1 of 2 different cementation techniques. In 26 consecutive
      patients, the pegged glenoid component was cemented with a traditional minimal
      manual pressurization technique, whereas 74 underwent a contemporary 3-step
      pressurization cementation technique before implant insertion. The first
      postoperative radiograph was evaluated using the system of Lazarus et al, looking
      at the frequency of lucent lines. The radiographs were deidentified and were
      randomized and evaluated by 2 independent observers on 3 separate occasions.
      RESULTS: The Kruskal-Wallis test showed significant differences between grades of
      radiolucent lines for pressurized versus unpressurized cementation techniques.
      There were significantly (P < .05) fewer lucent lines identified in the group
      that underwent contemporary 3-step pressurization as opposed to the group that
      underwent minimal manual pressurization. Intraobserver reliability and
      interobserver reliability with Cronbach alpha coefficients were good. CONCLUSION:
      The 3-step pressurized cementation technique resulted in a low incidence of
      radiolucent lines around the glenoid implant in patients undergoing TSA. LEVEL OF
      EVIDENCE: Level II, Prospective Cohort, Treatment Study.

PMID- 22960148
TI  - Loss of cardioprotection with ischemic preconditioning in aging hearts: role of
      sirtuin 1?
AB  - The effectiveness of ischemic preconditioning (IPC) to protect the heart against
      ischemia/reperfusion injury (IRI) declines with age. The deacetylase protein
      sirtuin 1 (Sirt 1) confers myriad functions including longevity and
      cardioprotection against IRI. As such, Sirt 1 may be a potential candidate to
      explain the protective effect of IPC. We aim to explore the role of Sirt 1 in the
      loss of the cardioprotective effect of IPC with age. Isolated hearts from young
      (9 weeks) and older (12-18 months) Long-Evans rats were subjected to 30 minutes
      of global ischemia and 60 minutes of reperfusion. Preconditioning stimuli were
      applied with either 2 cycles of 5-minute ischemia/reperfusion or with the potent
      Sirt 1 agonist resveratrol (RSV, 10 umol/L) for 15 minutes followed by a 10
      minute washout before the sustained ischemia. Both IPC and RSV significantly
      enhanced the functional recovery of young hearts by 168% (P < .001 vs control)
      and 65% (P < .01 vs control), respectively, and concomitantly reduced the infarct
      size by 65% and 45%, but the effect was blunted in older hearts. Administration
      of the selective Sirt 1 inhibitor III to young hearts did not alter the
      protective effect of IPC. Following ischemia/reperfusion, higher Sirt 1
      deacetylase activity was detected in older hearts compared to young hearts (0.48
      +/- 0.13 arbitrary units [AU] vs 0.17 +/- 0.03 AU, P < .01) and IPC did not alter
      Sirt 1 deacetylase activity. In conclusion, although Sirt 1 deacetylase activity
      is increased with age during ischemia/reperfusion, our data suggest that the loss
      of the cardioprotective effect of IPC in older animals is likely to be
      independent of Sirt 1.

PMID- 22960149
TI  - Greater sensitivity to nonaccidental than metric changes in the relations between
      simple shapes in the lateral occipital cortex.
AB  - Behavioral studies and single cell recordings in monkey inferotemporal cortex
      have documented greater sensitivity to differences in viewpoint invariant or
      nonaccidental properties (e.g., straight vs. curved), than metric properties
      (e.g., degree of curvature) of simple shapes. Are we similarly more sensitive to
      nonaccidental (NAP) than metric (MP) differences of the relations between
      objects? We addressed this question with sets of scene triplets that could, from
      a reference or "Base" scene (e.g., a brick slightly separated from a cylinder),
      undergo a NAP relational change (e.g., the brick attached to the cylinder) or an
      MP relational change (e.g., the brick further separated from the cylinder).
      Critically, both relational variations were matched in physical dissimilarity
      using pixel energy and the Gabor-jet system, a model of V1 similarity. In an
      adaptive staircase match-to-sample paradigm, subjects required more than double
      the presentation durations for detecting differences in MP than NAP relations to
      achieve equivalent levels of accuracy. In two fMRI experiments, NAP changes
      consistently produced greater responses in the lateral occipital cortex (LO), but
      not in earlier retinotopic stages, compared to MP changes, implicating LO as the
      potential neural locus for where the greater detectability of the differences of
      NAPs than MPs is made explicit. HMAX, a model of cell tuning in higher-level
      ventral visual areas, did not consistently reflect the marked NAP advantage
      witnessed in behavioral performance and in LO responses.

PMID- 22960150
TI  - Single-scan R2(*) measurement with macroscopic field inhomogeneity correction.
AB  - Accurate quantification of R2(*) (=1/T2(*)) is important for many applications in
      neuroimaging. However, R2(*) measurements made using conventional multi-echo
      gradient echo imaging are hampered by macroscopic field inhomogeneities. Several
      methods for compensation of macroscopic field inhomogeneities have been
      introduced, most of them requiring increased scan time. In this paper, an R2(*)
      estimation process using a modified multi-echo gradient echo sequence that
      includes bipolar compensation gradients and does not require additional data
      acquisition time is proposed. A post-processing algorithm based on an excitation
      profile weighted signal model is used. The optimal amount of compensation
      gradients and performance was investigated by numerical simulation and phantom
      tests. Multi-slice R2(*) maps were obtained from 11 human volunteers at 3T.
      Simulation results demonstrated that this method successfully removes the effects
      of macroscopic field inhomogeneities of up to +/- 300MUT/m within an error range
      of +/- 8%. ROI analysis revealed R2(*) values of 30.4 +/- 3.0s-1 (substantia
      nigra), 25.8 +/- 2.7s-1 (red nuclei), 23.2 +/- 1.0s-1 (genu), 20.8 +/- 1.2s-1
      (putamen), 34.2 +/- 3.4s-1 (globus pallidus), and 21.8 +/- 1.4s-1 (splenium)
      using the proposed method, with statistically significant differences compared to
      conventional method in the regions of the substantia nigra, red nucleus, genu,
      putamen, and globus pallidus (p<0.05). Our proposed scheme allows for fast single
      scan multi-slice R2(*) measurement and includes compensation for the effects of
      macroscopic field inhomogeneity.

PMID- 22960151
TI  - It is not all about phase: amplitude dynamics in corticomuscular interactions.
AB  - Corticomuscular interactions are studied mostly with EEG/EMG coherence, which,
      however, does not allow quantification of amplitude dynamics of sensorimotor
      oscillations. Here, we investigated the amplitude dynamics of sensorimotor EEG
      beta oscillations during an isometric task and their relation to corticomuscular
      coherence (CMC). We used amplitude envelopes of beta oscillations, derived from
      multichannel EEG and EMG recordings, as a measure of local cortical and spinal
      cord synchronization. In general, we showed that the amplitude of cortical beta
      oscillations can influence CMC in two ways. First, we showed that the signal-to
      noise ratio of pre-stimulus beta oscillations affects CMC. Second, we
      demonstrated that the attenuation of beta oscillations upon imperative stimulus
      correlated with the CMC strength. Attenuation of cortical beta oscillations was
      previously hypothesized to reflect increased motor cortex excitability.
      Consequently, this correlation might indicate that high cortical excitability,
      produced by imperative stimulus, facilitates the recruitment of neuronal networks
      responsible for establishing reliable corticospinal control manifested in larger
      CMC. Critically, we demonstrated that the amplitude envelopes of beta
      oscillations in EEG and EMG are positively correlated on time scales ranging from
      50 to 1000 ms. Such correlations indicate that the amplitude of cortical beta
      oscillations might relate to the rhythmic spiking output of both corticospinal
      neurons and their spinal targets. Compared to CMC, however, amplitude-envelope
      correlations were detected in fewer cases, which might relate to a higher
      susceptibility of these correlations to signal-to-noise ratio. We conclude that
      EEG beta oscillations, originating from the sensorimotor cortex, can transmit not
      only their phase but also amplitude dynamics through the spinal motoneurons down
      to peripheral effectors.

PMID- 22960152
TI  - Layer-specific BOLD activation in awake monkey V1 revealed by ultra-high spatial
      resolution functional magnetic resonance imaging.
AB  - The laminar structure of the cortex has previously been explored both in non
      human primates and human subjects using high-resolution functional magnetic
      resonance imaging (fMRI). However, whether the spatial specificity of the blood
      oxygenation-level-dependent (BOLD) fMRI is sufficiently high to reveal lamina
      specific organization in the cortex reliably is still unclear. In this study we
      demonstrate for the first time the detection of such layer-specific activation in
      awake monkeys at the spatial resolution of 200 * 200 * 1000 MUm(3) in a vertical
      4.7 T scanner. Results collected in trained monkeys are high in contrast-to-noise
      ratio and low in motion artifacts. Isolation of laminar activation was aided by
      choosing the optimal slice orientation and thickness using a novel pial vein
      pattern analysis derived from optical imaging. We found that the percent change
      of GE-BOLD signal is the highest at a depth corresponding to layer IV. Changes in
      the middle layers (layer IV) were 30% greater than changes in the top layers
      (layers I-III), and 32% greater than the bottom layers (layers V/VI). The laminar
      distribution of BOLD signal correlates well with neural activity reported in the
      literature. Our results suggest that the high intrinsic spatial resolution of GE
      BOLD signal is sufficient for mapping sub-millimeter functional structures in
      awake monkeys. This degree of spatial specificity will be useful for mapping both
      laminar activations and columnar structures in the cerebral cortex.

PMID- 22960153
TI  - Enhanced frontoparietal network architectures following "gaze-contingent" versus
      "free-hand" motor learning.
AB  - Longitudinal changes in cortical function are known to accompany motor skills
      learning, and can be detected as an evolution in the activation map. These
      changes include attenuation in activation in the prefrontal cortex and increased
      activation in primary and secondary motor regions, the cerebellum and posterior
      parietal cortex. Despite this, comparatively little is known regarding the impact
      of the mode or type of training on the speed of activation map plasticity and on
      longitudinal variation in network architectures. To address this, we randomised
      twenty-one subjects to learn a complex motor tracking task delivered across six
      practice sessions in either "free-hand" or "gaze-contingent motor control" mode,
      during which frontoparietal cortical function was evaluated using functional near
      infrared spectroscopy. Results demonstrate that upon practice termination, gaze
      assisted learners had achieved superior technical performance compared to free
      hand learners. Furthermore, evolution in frontoparietal activation foci
      indicative of expertise was achieved at an earlier stage in practice amongst gaze
      assisted learners. Both groups exhibited economical small world topology;
      however, networks in learners randomised to gaze-assistance were less costly and
      showed higher values of local efficiency suggesting improved frontoparietal
      communication in this group. We conclude that the benefits of gaze-assisted motor
      learning are evidenced by improved technical accuracy, more rapid task
      internalisation and greater neuronal efficiency. This form of assisted motor
      learning may have occupational relevance for high precision control such as in
      surgery or following re-learning as part of stroke rehabilitation.

PMID- 22960154
TI  - The antiviral activity and mechanism of action of (S)-[3-hydroxy-2
      (phosphonomethoxy)propyl] (HPMP) nucleosides.
AB  - One class of compounds that has shown promise as antiviral agents are the (S)-[3
      hydroxy-2-(phosphonomethoxy)propyl] (HPMP) nucleosides, members of the broader
      class of acyclic nucleoside phosphonates. These HPMP nucleosides are nucleotide
      analogs and have been shown to be effective inhibitors of a wide range of DNA
      viruses. Prodrugs of these compounds, which achieve higher levels of the active
      metabolites within the cell, have an expanded activity spectrum that also
      includes RNA viruses and retroviruses. Because they are analogs of natural
      nucleotide substrates, HPMP nucleosides are predicted to target polymerases (DNA
      polymerases, RNA polymerases and reverse transcriptases), resulting in the
      inhibition of viral genome replication. Previous work using the replicative
      enzymes of different viruses including human cytomegalovirus (HCMV) and vaccinia
      virus DNA polymerases and human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase has shown that the activated forms of these compounds are
      substrates for viral polymerases and that incorporation of these compounds into
      either the primer strand or the template strand inhibits, but does not
      necessarily terminate, further nucleic acid synthesis. The activity of these
      compounds against other viruses that do not encode their own polymerases, like
      polyoma viruses and papilloma viruses, suggests that host cell DNA polymerases
      are also targeted. This complex mechanism of action and broad activity spectrum
      has implications for the development of resistance and host cell genome
      replication, and suggests these compounds may be effective against other viruses
      such as influenza virus, respiratory syncytial virus and Dengue virus. This class
      of nucleotide analogs also points to a potential avenue for the development of
      newer antivirals.

PMID- 22960155
TI  - WFDC1/ps20: a host factor that influences the neutrophil response to murine
      hepatitis virus (MHV) 1 infection.
AB  - The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV
      infection. Herein we describe a contrasting role for ps20 in limiting MHV-1
      infection. Intranasal MHV-1 infection produces a respiratory infection in mice.
      Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection
      results in increased lung viral titers in ps20(-/-) compared to ps20(+/+) mice.
      Accompanying MHV-1 infection we observe an increase in the number of neutrophils
      infiltrating the BAL and an increase in the percentage of neutrophils in the lung
      draining lymph nodes of ps20(-/-) compared with ps20(+/+) mice. Gene expression
      levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the
      lungs of ps20(-/-) mice post-MHV-1 infection. Characterization of the immune cell
      profile in naive ps20(-/-) mice revealed an increase in circulating neutrophils
      compared to ps20(+/+) mice. No notable differences in other immune cell profiles
      were observed between the ps20(+/+) and ps20(-/-) mice. Accordingly, we examined
      MHV-1 infection of neutrophils and provide evidence that neutrophils isolated
      from ps20(-/-) mice are more susceptible to MHV-1 infection than neutrophils
      isolated from ps20(+/+) mice. These data suggest roles for ps20 in regulating
      expression of neutrophil-specific chemotactic factors, thereby potentially
      modulating neutrophil migration, and in modulating neutrophil susceptibility to
      MHV-1 infection.

PMID- 22960158
TI  - Arizona at the center of the U.S. immigration debate: U.S. supreme court rules on
      controversial state immigration law S.B. 1070.

PMID- 22960157
TI  - Dihydroceramide delays cell cycle G1/S transition via activation of ER stress and
      induction of autophagy.
AB  - Dihydroceramides, the precursors of ceramides in the de novo sphingolipid
      synthesis, have been recently implicated in active signalling. We previously
      demonstrated that dihydroceramide accumulation, in response to treatment with the
      dihydroceramide desaturase inhibitor XM462, induced autophagy with no sign of
      cell death in the gastric carcinoma HCG27 cell line. Here we show that XM462
      treatment induces a transient early increase in dihydroceramides that are
      successively metabolized into other sphingolipids. Dihydroceramides accumulation
      is associated with cyclin D1 expression modulation, delayed G1/S transition of
      cell cycle and increased autophagy. Moreover, XM462 treatment induces ER stress
      via the activation of the translation inhibitor eIF2alpha and the pro-survival
      transcriptional factor Xbp1. Exogenous addition of a short chain dihydroceramide
      analog reproduces the effects of endogenous accumulation of dihydroceramides,
      causing cell cycle delay of the G1/S transition, autophagy enhancement, eIF2alpha
      activation and Xbp1 splicing. Blocking autophagy with 3-methyladenine abrogates
      the effect of XM462 on cell cycle and reduces cell survival to XM462 treatment.
      Furthermore, the XM462-induced survival response is able to reduce etoposide
      toxicity in HCG27 and HCT116 cancer cells. Our data suggest a role of
      dihydroceramide in regulating cell proliferation and survival.

PMID- 22960159
TI  - Airport screening and spinal implants.

PMID- 22960156
TI  - Melatonin: an underappreciated player in retinal physiology and pathophysiology.
AB  - In the vertebrate retina, melatonin is synthesized by the photoreceptors with
      high levels of melatonin at night and lower levels during the day. Melatonin
      exerts its influence by interacting with a family of G-protein-coupled receptors
      that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging
      to the subtypes MT(1) and MT(2) have been identified in the mammalian retina.
      MT(1) and MT(2) receptors are found in all layers of the neural retina and in the
      retinal pigmented epithelium. Melatonin in the eye is believed to be involved in
      the modulation of many important retinal functions; it can modulate the
      electroretinogram (ERG), and administration of exogenous melatonin increases
      light-induced photoreceptor degeneration. Melatonin may also have protective
      effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A
      series of studies have implicated melatonin in the pathogenesis of age-related
      macular degeneration, and melatonin administration may represent a useful
      approach to prevent and treat glaucoma. Melatonin is used by millions of people
      around the world to retard aging, improve sleep performance, mitigate jet lag
      symptoms, and treat depression. Administration of exogenous melatonin at night
      may also be beneficial for ocular health, but additional investigation is needed
      to establish its potential.

PMID- 22960161
TI  - Better measurement for healthier places.

PMID- 22960160
TI  - Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert
      cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor
      activity in mice.
AB  - We are investigating treatments for cocaine abuse based on viral gene transfer of
      a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can
      reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug
      seeking behavior in rats for many months. Here, in mice, we explored the
      possibility that anti-cocaine antibodies can complement the actions of CocH to
      reduce cocaine uptake in brain and block centrally-evoked locomotor stimulation.
      Direct injections of test proteins showed that CocH (0.3 or 1mg/kg) was effective
      by itself in reducing drug levels in plasma and brain of mice given cocaine
      (10mg/kg, s.c., or 20mg/kg, i.p). Administration of cocaine antibody per se at a
      low dose (8 mg/kg, i.p.) exerted little effect on cocaine distribution. However,
      a higher dose of antibody (12 mg/kg) caused peripheral trapping (increased plasma
      drug levels), which led to increased cocaine metabolism by CocH, as evidenced by
      a 6-fold rise in plasma benzoic acid. Behavioral tests with small doses of CocH
      and antibody (1 and 8 mg/kg, respectively) showed that neither agent alone
      reduced mouse locomotor activity triggered by a very large cocaine dose
      (100mg/kg, i.p.). However, dual treatment completely suppressed the locomotor
      stimulation. Altogether, we found cooperative and possibly synergistic actions
      that warrant further exploration of dual therapies for treatment of cocaine
      abuse.

PMID- 22960162
TI  - Healthy Habits, Happy Homes: methods and baseline data of a randomized controlled
      trial to improve household routines for obesity prevention.
AB  - OBJECTIVE: To develop a home-based intervention for parents of 2-5 year old
      children to promote household routines to prevent overweight/obesity. METHODS: We
      recruited 121 children from health centers in Boston between 2011 and 2012 and
      randomized 62 to intervention and 59 to the control condition. The 6-month
      intervention included 1) motivational coaching at home and by phone with a health
      educator, 2) mailed educational materials, and 3) weekly text messages. The
      intervention promoted three household routines: eating meals as a family,
      obtaining adequate sleep, and limiting screen time. RESULTS: Of the 121 children,
      mean (SD) age was 4.0 (1.1) years; 52% were Hispanic, 34% Black, and 14%
      White/Other. Nearly 60% of the sample had annual household incomes <= $20,000.
      Approximately 64% of families reported eating together >= 7 times per week,
      however, many meals were eaten in front of a TV. Over half of the children slept
      less than the recommended 11h/night and 78% viewed >= 2 h/day of screen time.
      CONCLUSIONS: Household routines that increase obesity risk were prevalent among
      low-income families in this study. If proven to be effective, promotion of
      household routines related to family meals, sleep, and screen time may prevent
      young children from becoming overweight/obese.

PMID- 22960164
TI  - Computer simulation of ECG manifestations of left ventricular electrical
      remodeling.
AB  - An increased QRS voltage is considered to be specific for the electrocardiogram
      (ECG) diagnosis of left ventricular hypertrophy (LVH). However, the QRS-complex
      patterns in patients with LVH cover a broader spectrum: increased QRS voltage,
      prolonged QRS duration, left axis deviation, and left anterior fascicular block-
      and left bundle branch block-like patterns, as well as pseudo-normal QRS
      patterns. The classical interpretation of the QRS patterns in LVH relates these
      changes to increased left ventricular mass (LVM) per se, while tending to neglect
      the modified active and passive electrical properties of the myocardium. However,
      it has been well documented that both active and passive electrical properties in
      LVH are altered. Using computer simulations, we have shown that an increased LVM
      is not the only determinant of QRS complex changes in LVH, as these changes could
      also be produced without changing the left ventricular mass, implying that these
      QRS patterns can be present in patients before their LVM exceeds the arbitrary
      upper normal limits. Our results link the experimental evidence on electrical
      remodeling with clinical interpretation of ECG changes in patients with LVH and
      stress the necessity of a complex interpretation of the QRS patterns considering
      both spatial and nonspatial determinants in terms of the spatial angle theory. We
      assume that hypertrophic electrical remodeling in combination with changes in
      left ventricular size and shape explains the variety of ECG patterns as well as
      the discrepancies between ECG and left ventricular mass.

PMID- 22960163
TI  - Hemisection spinal cord injury in rat: the value of intraoperative somatosensory
      evoked potential monitoring.
AB  - Techniques used to produce partial spinal cord injuries in animal models have the
      potential for creating variability in lesions. The amount of tissue affected may
      influence the functional outcomes assessed in the animals. The recording of
      somatosensory evoked potentials (SSEPs) may be a valuable tool for assessing the
      extent of lesion applied in animal models of traumatic spinal cord injury (SCI).
      Intraoperative tibial SSEP recordings were assessed during surgically induced
      lateral thoracic hemisection SCI in Sprague-Dawley rats. The transmission of
      SSEPs, or lack thereof, was determined and compared against the integrity of the
      dorsal funiculi on each side of the spinal cord upon histological sectioning. An
      association was found between the presence of an SSEP signal and presence of
      intact dorsal funiculus tissue. The relative risk is 4.50 (95% confidence
      interval: 1.83-11.08) for having an intact dorsal funiculus when the ipsilateral
      SSEP was present compared to when it was absent. Additionally, the amount of
      spared spinal cord tissue correlates with final functional assessments at nine
      weeks post injury: BBB (linear regression, R2=0.618, p<0.001) and treadmill test
      (linear regression, R2=0.369, p=0.016). Therefore, we propose intraoperative SSEP
      monitoring as a valuable tool to assess extent of lesion and reduce variability
      between animals in experimental studies of SCI.

PMID- 22960165
TI  - Assessment of the sensitivity of detecting drug-induced QTc changes using subject
      specific rate correction.
AB  - AIMS: To quantify the sensitivity of QT heart-rate correction methods for
      detecting drug-induced QTc changes in thorough QT studies. METHODS: Twenty-four
      hour Holter ECGs were analyzed in 66 normal subjects during placebo and
      moxifloxacin delivery (single oral dose). QT and RR time series were extracted.
      Three QTc computation methods were used: (1) Fridericia's formula, (2)
      Fridericia's formula with hysteresis reduction, and (3) a subject-specific
      approach with transfer function-based hysteresis reduction and three-parameter
      non-linear fitting of the QT-RR relation. QTc distributions after placebo and
      moxifloxacin delivery were compared in sliding time windows using receiver
      operating characteristic (ROC) curves. The area under the ROC curve (AUC) served
      as a measure to quantify the ability of each method to detect moxifloxacin
      induced QTc prolongation. RESULTS: Moxifloxacin prolonged the QTc by 10.6 +/- 6.6
      ms at peak effect. The AUC was significantly larger after hysteresis reduction
      (0.87 +/- 0.13 vs. 0.82 +/- 0.12, p<0.01) at peak effect, indicating a better
      discriminating capability. Subject-specific correction further increased the AUC
      to 0.91 +/- 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The
      performance of the subject-specific approach was the consequence of a
      substantially lower intra-subject QTc standard deviation (5.7 +/- 1.1 ms vs. 8.8
      +/- 1.2 ms for Fridericia). CONCLUSION: The ROC curve provides a tool for
      quantitative comparison of QT heart rate correction methods in the context of
      detecting drug-induced QTc prolongation. Results support a broader use of subject
      specific QT correction.

PMID- 22960166
TI  - Microvolt-level T-wave alternans determination using the spectral method in
      patients with QT prolongation: value of adjusting the T-wave window.
AB  - BACKGROUND: Microvolt-level T-wave alternans (MTWA) measured by the spectral
      method is a useful risk predictor for sudden cardiac death because of its high
      negative predictive value. MTWA analysis software selects a segment of the ECG
      that encompasses the T-wave in most individuals, but may miss the T-wave end in
      patients with QT prolongation. HYPOTHESES: (1) In patients with QT prolongation,
      adjustment of the T-wave window will increase the sensitivity of MTWA detection.
      (2) The extent of T-wave window adjustment needed will correspond to the degree
      of QT prolongation. METHODS: Using data from long-QT syndrome patients, including
      QTc <0.45 s (normal), 0.45-0.49 s (moderate prolongation), and >= 0.50s (severe
      prolongation), MTWA analysis was performed before and after T-wave window
      adjustment. RESULTS: Of 119 patients, 74% required T-wave window adjustment.
      There was a stronger association between the magnitude of the T-wave offset and
      the unadjusted QT than between the magnitude of the T-wave offset and QTc
      (Spearman correlation coefficient 0.690 vs. 0.485 respectively, P<.05). Of 99
      initially negative MTWA results, 4 became non-negative after adjustment of the T
      wave window (P<.05). All 8 initially positive studies and 12 initially
      indeterminate studies remained positive and indeterminate, respectively.
      CONCLUSIONS: T-wave window adjustment can enable detection of abnormal MTWA that
      otherwise would be classified as "negative" or "normal." Newly developed T-wave
      window adjustment software may further improve the negative predictive value of
      MTWA testing and should be validated in a structural heart disease population.

PMID- 22960167
TI  - Signal quality and data fusion for false alarm reduction in the intensive care
      unit.
AB  - Due to a lack of integration between different sensors, false alarms (FA) in the
      intensive care unit (ICU) are frequent and can lead to reduced standard of care.
      We present a novel framework for FA reduction using a machine learning approach
      to combine up to 114 signal quality and physiological features extracted from the
      electrocardiogram, photoplethysmograph, and optionally the arterial blood
      pressure waveform. A machine learning algorithm was trained and evaluated on a
      database of 4107 expert-labeled life-threatening arrhythmias, from 182 separate
      ICU visits. On the independent test data, FA suppression results with no true
      alarm (TA) suppression were 86.4% for asystole, 100% for extreme bradycardia and
      27.8% for extreme tachycardia. For the ventricular tachycardia alarms, the best
      FA suppression performance was 30.5% with a TA suppression rate below 1%. To
      reduce the TA suppression rate to zero, a reduction in FA suppression performance
      to 19.7% was required.

PMID- 22960168
TI  - A simple reporter assay for screening claudin-4 modulators.
AB  - Claudin-4, a member of a tetra-transmembrane protein family that comprises 27
      members, is a key functional and structural component of the tight junction-seal
      in mucosal epithelium. Modulation of the claudin-4-barrier for drug absorption is
      now of research interest. Disruption of the claudin-4-seal occurs during
      inflammation. Therefore, claudin-4 modulators (repressors and inducers) are
      promising candidates for drug development. However, claudin-4 modulators have
      never been fully developed. Here, we attempted to design a screening system for
      claudin-4 modulators by using a reporter assay. We prepared a plasmid vector
      coding a claudin-4 promoter-driven luciferase gene and established stable
      reporter gene-expressing cells. We identified thiabendazole, carotene and
      curcumin as claudin-4 inducers, and potassium carbonate as a claudin-4 repressor
      by using the reporter cells. They also increased or decreased, respectively, the
      integrity of the tight junction-seal in Caco-2 cells. This simple reporter system
      will be a powerful tool for the development of claudin-4 modulators.

PMID- 22960169
TI  - An efficient algorithm for DNA fragment assembly in MapReduce.
AB  - Fragment assembly is one of the most important problems of sequence assembly.
      Algorithms for DNA fragment assembly using de Bruijn graph have been widely used.
      These algorithms require a large amount of memory and running time to build the
      de Bruijn graph. Another drawback of the conventional de Bruijn approach is the
      loss of information. To overcome these shortcomings, this paper proposes a
      parallel strategy to construct de Bruijin graph. Its main characteristic is to
      avoid the division of de Bruijin graph. A novel fragment assembly algorithm based
      on our parallel strategy is implemented in the MapReduce framework. The
      experimental results show that the parallel strategy can effectively improve the
      computational efficiency and remove the memory limitations of the assembly
      algorithm based on Euler superpath. This paper provides a useful attempt to the
      assembly of large-scale genome sequence using Cloud Computing.

PMID- 22960171
TI  - Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through
      the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells.
AB  - Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has
      been shown to down-regulate inflammatory responses in dendritic cells (DCs);
      however, the underlying mechanism has not been understood. Recently, we
      identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In
      this study, we showed the molecular basis for the down-regulation of toll-like
      receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80,
      CD86, and MHC class I and II, which are molecules essential for antigen
      presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated
      DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory
      cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6)
      and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular
      signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and
      nuclear factor kappaB (NF-kappaB) p65 translocation through 67LR. Interestingly,
      we also found that EGCG markedly elevated the expression of the Tollip protein, a
      negative regulator of TLR signaling, through 67LR. These novel findings provide
      new insight into the understanding of negative regulatory mechanisms of the TLR4
      signaling pathway and consequent inflammatory responses that are implicated in
      the development and progression of many chronic diseases.

PMID- 22960170
TI  - An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma (aRMS) is a very aggressive sarcoma of children and
      young adults. Our previous studies have shown that small molecule inhibition of
      Pdgfra is initially very effective in an aRMS mouse model. However, slowly
      evolving, acquired resistance to a narrow-spectrum kinase inhibitor (imatinib)
      was common. We identified Src family kinases (SFKs) to be potentiators of Pdgfra
      in murine aRMS primary cell cultures from mouse tumors with evolved resistance in
      vivo in comparison to untreated cultures. Treating the resistant primary cell
      cultures with a combination of Pdgfra and Src inhibitors had a strong additive
      effect on cell viability. In Pdgfra knockout tumors, however, the Src inhibitor
      had no effect on tumor cell viability. Sorafenib, whose targets include not only
      PDGFRA but also the Src downstream target Raf, was effective at inhibiting mouse
      and human tumor cell growth and halted progression of mouse aRMS tumors in vivo.
      These results suggest that an adaptive Src-Pdgfra-Raf-Mapk axis is relevant to
      PDGFRA inhibition in rhabdomyosarcoma.

PMID- 22960172
TI  - Viral Toll Like Receptor activation of pulmonary vascular smooth muscle cells
      results in endothelin-1 generation; relevance to pathogenesis of pulmonary
      arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare but fatal condition in which
      raised pulmonary vascular resistance leads to right heart failure and death.
      Endothelin-1 is a potent endogenous vasoconstrictor, which is considered to be
      central to many of the events that lead to PAH, and is an important therapeutic
      target in the treatment of the condition. In many cases of PAH, the aetiology is
      unknown but inflammation is increasingly thought to play an important role and
      viruses have been implicated in the development of disease. The Toll Like
      Receptors (TLRs) play a key role in innate immune responses by initiating
      specific anti-bacterial and anti-viral defences in recognition of signature
      molecular motifs on the surface of invading pathogens. In this study, we set out
      to examine the expression of bacterial and viral TLRs in human pulmonary artery
      smooth muscle cells and to establish whether their activation could be relevant
      to PAH. We found that the viral TLR3 and bacterial TLRs 4 and 6 were most
      abundantly expressed in human pulmonary artery smooth muscle cells. Using
      specific TLR ligands, we found that activation of TLRs 3 and 4 resulted in IL-8
      release by human pulmonary artery smooth muscle cells but that only TLR3
      stimulation resulted in IP10 and endothelin-1 release. These data suggest that
      human pulmonary artery smooth muscle cells express significant levels of viral
      TLR3 and respond to its activation by releasing endothelin-1. This may have
      importance in understanding the association between viruses and the development
      of PAH.

PMID- 22960173
TI  - Lubiprostone activates CFTR, but not ClC-2, via the prostaglandin receptor
      (EP(4)).
AB  - The goal of this study was to determine the mechanism of lubiprostone activation
      of epithelial chloride transport. Lubiprostone is a bicyclic fatty acid approved
      for the treatment of constipation [1]. There is uncertainty, however, as to how
      lubiprostone increases epithelial chloride transport. Direct stimulation of ClC-2
      and CFTR chloride channels as well as stimulation of these channels via the EP(4)
      receptor has been described [2-5]. To better define this mechanism, two-electrode
      voltage clamp was used to assay Xenopus oocytes expressing ClC-2, with or without
      co-expression of the EP(4) receptor or beta adrenergic receptor (betaAR), for
      changes in conductance elicited by lubiprostone. Oocytes co-expressing CFTR and
      either betaAR or the EP(4) receptor were also studied. In oocytes co-expressing
      ClC-2 and betaAR conductance was stimulated by hyperpolarization and acidic pH
      (pH = 6), but there was no response to the beta adrenergic agonist,
      isoproterenol. Oocytes expressing ClC-2 only or co-expressing ClC-2 and EP(4) did
      not respond to the presence of 0.1, 1, or 10 MUM lubiprostone in the
      superperfusate. Oocytes co-expressing CFTR and betaAR did not respond to
      hyperpolarization, acidic pH, or 1 MUM lubiprostone. However, conductance was
      elevated by isoproterenol and inhibited by CFTR(inh)172. Co-expression of CFTR
      and EP(4) resulted in lubiprostone-stimulated conductance, which was also
      sensitive to CFTR(inh)172. The EC(50) for lubiprostone mediated CFTR activation
      was ~10 nM. These results demonstrate no direct action of lubiprostone on either
      ClC-2 or CFTR channels expressed in oocytes. However, the results confirm that
      CFTR can be activated by lubiprostone via the EP(4) receptor in oocytes.

PMID- 22960174
TI  - Resonance phenomenon of the ATP motor as an ultrasensitive biosensor.
AB  - We designed a rotary biosensor as a damping effector, with the rotation of the
      F(0)F(1)-ATPase driven by Adenosine Triphosphate (ATP) synthesis being indicated
      by the fluorescence intensity and a damping effect force being induced by the
      binding of an RNA molecule to its probe on the rotary biosensor. We found that
      the damping effect could contribute to the resonance phenomenon and energy
      transfer process of our rotary biosensor in the liquid phase. This result
      indicates that the ability of the rotary motor to operate in the vibration
      harmonic mode depends on the environmental conditions and mechanism in that a few
      molecules of the rotary biosensor could induce all of the sensor molecules to
      fluoresce together. These findings contribute to the theory study of the ATPase
      motor and future development of biosensors for ultrasensitive detection.

PMID- 22960175
TI  - ANG-(1-7) reduces ANG II-induced insulin resistance by enhancing Akt
      phosphorylation via a Mas receptor-dependent mechanism in rat skeletal muscle.
AB  - The nonapeptide angiotensin II (ANG II) induces vasoconstriction via the ANG II
      type I receptor, while its splice product ANG-(1-7) elicits an antihypertensive
      effect via the Mas receptor. Although a critical role of ANG II in the etiology
      of skeletal muscle insulin resistance is well documented, the role of the ANG-(1
      7)/Mas receptor axis in this context is poorly understood. Therefore, we
      determined whether ANG-(1-7) is effective in ameliorating the negative effects of
      ANG II on insulin-stimulated insulin signaling and glucose transport activity in
      isolated soleus muscle from normotensive lean Zucker rats. ANG II alone (500 nM
      for 2 h) decreased insulin-stimulated glucose transport activity by 45% (P <
      0.05). In the presence of 500-1000 nM ANG-(1-7), insulin-stimulated glucose
      transport activity in muscle exposed to ANG II improved by ~30% (P < 0.05).
      Moreover, ANG-(1-7) treatment increased Akt Ser(473) phosphorylation (47%, P <
      0.05) without an effect on glycogen synthase kinase-3beta Ser(9) phosphorylation.
      The dependence of ANG-(1-7) action on the Mas receptor was assessed using A779
      peptide, a selective Mas receptor antagonist. The positive effects of ANG-(1-7)
      on insulin-stimulated glucose transport activity and Akt Ser(473) phosphorylation
      in soleus muscle were completely prevented in presence of 1000 nM A779. In
      conclusion, the present study demonstrates that ANG-(1-7), via a Mas receptor
      dependent mechanism, can ameliorate the inhibitory effect of ANG II on glucose
      transport activity in mammalian skeletal muscle, associated with enhanced Akt
      phosphorylation. These results provide further evidence supporting the targeting
      of the renin-angiotensin system for interventions designed to reduce insulin
      resistance in skeletal muscle tissue.

PMID- 22960176
TI  - Sphingosine kinase-1/sphingosine-1-phosphate receptor type 1 signalling axis is
      induced by transforming growth factor-beta1 and stimulates cell migration in
      RAW264.7 macrophages.
AB  - Macrophage recruitment to sites of inflammation is an essential step in host
      defense. However, the signals regulating the mobilization of these cells are
      still not fully understood. Sphingosine-1-phosphate (S1P), a pleiotropic
      bioactive lipid mediator, is known to regulate an array of biological activities
      in various cell types. Here, we investigated the roles of S1P and S1P receptors
      (S1PRs) in macrophage migration in vitro. Furthermore, we explored the cross-talk
      between transforming growth factor-beta1 (TGF-beta1) and S1P signalling pathways
      in this process. We found that S1P exerted a powerful migratory action on
      RAW264.7 macrophages, as determined in Boyden chambers. Moreover, by employing
      RNA interference technology and pharmacological tools, we have demonstrated that
      S1PR1, but not S1PR2 and S1PR3, is required for S1P-induced macrophage migration.
      Importantly, we observed a pronounced increase in sphingosine kinase-1 (SphK1)
      mRNA expression and subsequently increase in S1P production, following
      transforming growth factor-beta1 (TGF-beta1) stimulation in RAW264.7 macrophages.
      The expression of S1PR1, but not S1PR2 and S1PR3, was also significantly up
      regulated after TGF-beta1 stimulation. Interestingly, exogenously added S1P
      induced up-regulation of SphK1 and the synthesis of additional S1P, suggesting a
      self-amplifying loop of S1P to enhance macrophage migration. In conclusion, our
      results reveal that SphK1/S1PR1 signalling axis is induced by TGF-beta1 and
      stimulates cell migration in RAW 264.7 macrophages. This study provides new clues
      for the molecular mechanisms of macrophage recruitment during inflammation.

PMID- 22960177
TI  - Differentiating multipotent mesenchymal stromal cells generate factors that exert
      paracrine activities on exogenous MSCs: Implications for paracrine activities in
      bone regeneration.
AB  - The mechanisms by which multipotent mesenchymal stromal cells (MSCs) contribute
      to tissue repair following transplantation into host tissues remains poorly
      understood. Current concepts suggest that, in addition to differentiation into
      cells of the host tissues, MSCs also generate trophic factors that modulate host
      tissue microenvironment to aid in the repair process. In this communication, we
      assessed whether factors secreted by MSCs undergoing osteogenic differentiation
      induce expression of osteoblast markers in exogenous MSCs as well as their
      migration. Murine MSCs were cultured in osteogenic medium, and at different time
      points, medium conditioned by the cells was collected and assessed for its
      effects on differentiation and migration of exogenous MSCs. In addition, we
      determined whether MSCs infused into mice femurs expressed genes encoding for
      factors predicted to play a role in paracrine activities. The results showed that
      MSCs maintained in osteogenic medium, secreted factors at specific time points
      that induced alkaline phosphatase activity (ALP) in exogenous MSCs as well as
      their migration. MSCs infused into mice femurs and retrieved at different days
      expressed genes that encoded predicted factors that play a role in cell
      differentiation and migration. Neutralizing antibodies to bone morphogenetic
      protein-2 (BMP-2) led to the decrease in ALP activity by exogenous MSCs. These
      data demonstrated that, as MSCs differentiate toward osteogenic lineage, they
      secrete factors that induce recruitment and differentiation of endogenous
      progenitors. These data reveal mechanisms by which donor MSCs may contribute to
      the bone reparative process and provide a platform for designing approaches for
      stem cell therapies of musculoskeletal disorders.

PMID- 22960178
TI  - FGF signaling via MAPK is required early and improves Activin A-induced
      definitive endoderm formation from human embryonic stem cells.
AB  - Considering their unlimited proliferation and pluripotency properties, human
      embryonic stem cells (hESCs) constitute a promising resource applicable for cell
      replacement therapy. To facilitate this clinical translation, it is critical to
      study and understand the early stage of hESCs differentiation wherein germ layers
      are defined. In this study, we examined the role of FGF signaling in Activin A
      induced definitive endoderm (DE) differentiation in the absence of supplemented
      animal serum. We found that activated FGF/MAPK signaling is required at the early
      time point of Activin A-induced DE formation. In addition, FGF activation
      increased the number of DE cells compared to Activin A alone. These DE cells
      could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors
      in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently
      induce DE cells in the absence of serum. These findings improve our understanding
      of human endoderm formation, and constitute a step forward in the generation of
      clinical grade hESCs progenies for cell therapy.

PMID- 22960179
TI  - Inducible nitric oxide synthase aggresome formation is mediated by nitric oxide.
AB  - Nitric oxide (NO) generated by inducible NO synthase (iNOS) contributes
      critically to inflammatory injury and host defense. While previously thought as a
      soluble protein, iNOS was recently reported to form aggresomes inside cells. But
      what causes iNOS aggresome formation is unknown. Here we provide evidence
      demonstrating that iNOS aggresome formation is mediated by its own product NO.
      Exposure to inflammatory stimuli (lipopolysaccharide and interferon-gamma)
      induced robust iNOS expression in mouse macrophages. While initially existing as
      a soluble protein, iNOS progressively formed protein aggregates as a function of
      time. Aggregated iNOS was inactive. Treating the cells with the NOS inhibitor N
      nitro-L-arginine methyl ester (L-NAME) blocked NO production from iNOS without
      affecting iNOS expression. However, iNOS aggregation in cells was prevented by L
      NAME. The preventing effect of NO blockade on iNOS aggresome formation was
      directly observed in GFP-iNOS-transfected cells by fluorescence imaging.
      Moreover, iNOS aggresome formation could be recaptured by adding exogenous NO to
      L-NAME-treated cells. These studies demonstrate that iNOS aggresome formation is
      caused by NO. The finding that NO induces iNOS aggregation and inactivation
      suggests aggresome formation as a feedback inhibition mechanism in iNOS
      regulation.

PMID- 22960180
TI  - Brassinosteroid-induced CO(2) assimilation is associated with increased stability
      of redox-sensitive photosynthetic enzymes in the chloroplasts in cucumber plants.
AB  - Brassinosteroids (BRs) play important roles in plant growth, development,
      photosynthesis and stress tolerance; however, the mechanism underlying BR
      enhanced photosynthesis is currently unclear. Here, we provide evidence that an
      increase in the BR level increased the quantum yield of PSII, activities of
      Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase), and CO(2)
      assimilation. BRs upregulated the transcript levels of genes and activity of
      enzymes involved in the ascorbate-glutathione cycle in the chloroplasts, leading
      to an increased ratio of reduced (GSH) to oxidized (GSSG) glutathione in the
      chloroplasts. An increased GSH/GSSG ratio protected RCA from proteolytic
      digestion and increased the stability of redox-sensitive enzymes in the
      chloroplasts. These results strongly suggest that BRs are capable of regulating
      the glutathione redox state in the chloroplasts through the activation of the
      ascorbate-glutathione cycle. The resulting increase in the chloroplast thiol
      reduction state promotes CO(2) assimilation, at least in part, by enhancing the
      stability and activity of redox-sensitive photosynthetic enzymes through post
      translational modifications.

PMID- 22960181
TI  - Crystal structure of 1,3Gal43A, an exo-beta-1,3-galactanase from Clostridium
      thermocellum.
AB  - Glycoside hydrolase family 43 (GH43) consists of a variety of enzymes distributed
      widely in prokaryotes and eukaryotes. The mechanism by which GH43 enzymes
      hydrolyze oligosaccharides requires three essential acidic amino acid residues.
      However, one of them is thought to be missing in galactan beta-1,3-galactosidases
      from the GH43 family. Ct1,3Gal43A, from Clostridium thermocellum, is comprised of
      a GH43 domain, a CBM13 domain, and a dockerin domain and exhibits an unusual
      ability to hydrolyze beta-1,3-galactan in the presence of a beta-1,6 linked
      branch. Here, we present its crystal structure at 2.7 A resolution and complex
      structures of the enzyme with several substrates and analogs. Two modes of
      substrate binding were observed at the beta site of the CtCBM13 domain, and one
      galactobiose molecule was found in an "L" shaped pocket of the CtGH43 domain,
      which appears large enough to accommodate two more galactose units. In addition,
      we found that mutating Glu112 to Gln or Ala eliminated the galactan hydrolysis
      activity of Ct1,3Gal43A while did not disrupt its ligand binding ability.
      Combining this results and the crystal structure we identified Glu112 in
      Ct1,3Gal43A as the 'missing' essential acidic residue in galactan beta-1,3
      galactosidases. Structural information presented here also suggests a mechanism
      by which Ct1,3Gal43A bypasses beta-1,6 linked branches in the substrate and
      another mechanism by which the substrate is delivered 'in trans' from the CBM13
      domain to the catalytic GH43 domain.

PMID- 22960182
TI  - The generation of a 1-hydroxy-2-naphthoate 1,2-dioxygenase by single point
      mutations of salicylate 1,2-dioxygenase--rational design of mutants and the
      crystal structures of the A85H and W104Y variants.
AB  - Key amino acid residues of the salicylate 1,2-dioxygenase (SDO), an iron (II)
      class III ring cleaving dioxygenase from Pseudaminobacter salicylatoxidans BN12,
      were selected, based on amino acid sequence alignments and structural analysis of
      the enzyme, and modified by site-directed mutagenesis to obtain variant forms
      with altered catalytic properties. SDO shares with 1-hydroxy-2-naphthoate
      dioxygenase (1H2NDO) its unique ability to oxidatively cleave monohydroxylated
      aromatic compounds. Nevertheless SDO is more versatile with respect to 1H2NDO and
      other known gentisate dioxygenases (GDOs) because it cleaves not only gentisate
      and 1-hydroxy-2-naphthoate (1H2NC) but also salicylate and substituted
      salicylates. Several enzyme variants of SDO were rationally designed to simulate
      1H2NDO. The basic kinetic parameters for the SDO mutants L38Q, M46V, A85H and
      W104Y were determined. The enzyme variants L38Q, M46V, A85H demonstrated higher
      catalytic efficiencies toward 1-hydroxy-2-naphthoate (1H2NC) compared to
      gentisate. Remarkably, the enzyme variant A85H effectively cleaved 1H2NC but did
      not oxidize gentisate at all. The W104Y SDO mutant exhibited reduced reaction
      rates for all substrates tested. The crystal structures of the A85H and W104Y
      variants were solved and analyzed. The substitution of Ala85 with a histidine
      residue caused significant changes in the orientation of the loop containing this
      residue which is involved in the active site closing upon substrate binding. In
      SDO A85H this specific loop shifts away from the active site and thus opens the
      cavity favoring the binding of bulkier substrates. Since this loop also interacts
      with the N-terminal residues of the vicinal subunit, the structure and packing of
      the holoenzyme might be also affected.

PMID- 22960183
TI  - Effects of [123I]ADAM, a serotonin transporter radiopharmaceutical, on pregnant
      Sprague-Dawley rats.
AB  - Serotonin transport abnormalities are implicated in neuropsychiatric disorders.
      [(123)I]ADAM ([(123)I]-2-([2-({dimethylamino}methyl)phenyl]thio)-5
      iodophenylamine) is a novel radiotracer that targets serotonin transporters. We
      assessed the toxicity of [(123)I]ADAM (18.5 MBq) administered in early- and late
      phases (8 and 14 day postfertilization, respectively) of pregnancy. The
      mortality, clinical status, and gross necropsy were measured in pregnant rats,
      and the fertility index was measured in rat offspring (weight, clinical
      observations). We found no dosing-related clinical signs. In conclusion,
      [(123)I]ADAM was not toxic in an animal pregnancy model.

PMID- 22960184
TI  - Polarity and stratification of the epidermis.
AB  - Polarity is a fundamental property of epithelial cells. In this review, we
      discuss our current knowledge of the polarity of a stratified epithelium, the
      epidermis, focusing on similarities and differences with simple epithelial
      models. We highlight how the differences in tissue architecture and physiology
      result in alterations in some aspects of cell polarity. In addition, we discuss
      one of the most prominent uses for cell polarity in the epidermis-orienting the
      mitotic spindle to drive the stratification and differentiation of this tissue
      during development.

PMID- 22960185
TI  - The TASK1 channel inhibitor A293 shows efficacy in a mouse model of multiple
      sclerosis.
AB  - The two-pore domain potassium channel TASK1 (KCNK3) has recently emerged as an
      important modulator in autoimmune CNS inflammation. Previously, it was shown that
      T lymphocytes obtained from TASK1(-/-) mice display impaired T cell effector
      functions and that TASK1(-/-) mice show a significantly reduced disease severity
      in myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide induced experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We
      here evaluate a potent and specific TASK1 channel inhibitor, A293, which caused a
      dose-dependent reduction of T cell effector functions (cytokine production and
      proliferation). This effect was abolished in CD4(+) T cells from TASK1(-/-) mice
      but not in cells from TASK3(-/-) mice. In electrophysiological measurements, A293
      application induced a significant reduction of the outward current of wildtype T
      lymphocytes, while there was no effect in TASK1(-/-) cells. Preventive and
      therapeutic application of A293 significantly ameliorated the EAE disease course
      in wildtype mice while it had no significant effect in TASK1(-/-) mice and was
      still partly effective in TASK3(-/-) mice. In summary, our findings support the
      concept of TASK1 as an attractive drug target for autoimmune disorders.

PMID- 22960186
TI  - Relationship of nitric oxide synthase induction to peroxynitrite-mediated
      oxidative damage during the first week after experimental traumatic brain injury.
AB  - We have previously shown the pathophysiological importance of the reactive
      nitrogen species peroxynitrite (PN) formed from the reaction of nitric oxide
      (*NO) and superoxide (O(2)(*-)) radicals and its involvement in lipid
      peroxidation (LP) and protein nitration damage in brain tissue following
      traumatic brain injury (TBI). Nitric oxide is produced by at least three isoforms
      of the enzyme nitric oxide synthase (NOS) including: endothelial NOS (eNOS) in
      the CNS vasculature, neuronal NOS (nNOS), and inducible NOS (iNOS) in
      macrophages/microglia. In view of the requirement of *NO synthesis for PN
      formation, we sought to address the time course of NOS expression (mRNA by real
      time quantitative PCR and protein by western blot) after TBI in comparison with
      the time course of PN-mediated protein nitration (3-nitrotyrosine, 3-NT) in
      ipsilateral cortex (CTX) and hippocampus (HIPP) between 3 hours and 1 week post
      injury using a controlled cortical impact (CCI) mouse model of TBI in young adult
      CF-1 mice. Protein nitration showed a progressive posttraumatic increase that
      became significant in CTX at 24 hours and then peaked at 72 hours in both CTX and
      HIPP. During the increase in PN-derived 3-NT, there was no increase in either CTX
      or HIPP eNOS mRNA levels, whereas eNOS protein levels were significantly (p<0.05)
      increased at 48 and 72 hours in both brain regions. There was a significant
      decrease in HIPP, but not CTX nNOS mRNA; however, nNOS protein did not change
      except for a significant increase in CTX at 1 week. There was significantly
      increased CTX and HIPP iNOS mRNA levels at 24, 48, and 72 hours (p<.05) post
      injury. In contrast, no change was seen in CTX or HIPP iNOS protein at any
      timepoint. Taken together, eNOS protein expression and iNOS mRNA appear to bear a
      coincident temporal relationship to the time course of PN-mediated protein
      nitrative damage after CCI-TBI suggesting that both constitutive and inducible
      NOS isoforms contribute *NO for PN formation and 3-NT protein modification after
      TBI.

PMID- 22960187
TI  - Rapid epileptogenesis in the mouse pilocarpine model: video-EEG, pharmacokinetic
      and histopathological characterization.
AB  - Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy
      and several rodent models allow studying the pathophysiology of this disorder.
      One of the best characterized models of TLE is the pilocarpine model. The model
      has been widely used in rats, but relatively few studies report data obtained
      with mice. This triggered the present study to perform a comprehensive
      characterization of the mouse pilocarpine model. We used male NMRI mice (28-32 g)
      and first established the dose-response relationship for pilocarpine (250-400
      mg/kg; ip) to induce status epilepticus (SE). This enabled to define the optimal
      dose (300 mg/kg) producing the highest SE response (50%) associated with the best
      survival rate of the animals (90%). The impact of different durations of SE (0.5
      3.0 h) on the time to the onset of the first spontaneous recurrent seizures (SRS)
      was recorded during 5-day continuous video monitoring following the SE. Virtually
      no "latent" period was observed as the seizures appeared already within 24-48 h
      after the pilocarpine-induced SE and 0.5 h duration of the SE was sufficient to
      trigger SRS. Pharmacokinetics assessment showed that these seizures were not
      associated with residual pilocarpine exposure as it was cleared from the blood
      and brain already within 24 h post-injection. Consistent with previous reports
      from the rat pilocarpine model we observed that the extent of hippocampal
      reorganization and neuronal loss correlates with the duration of SE. However, the
      shorter durations of SE (0.5-2.0 h) appeared to produce cell loss restricted
      mainly to the hilus of the dentate gyrus. Interestingly, we also observed that
      the number of seizures occurring within 5 days after SE appeared to correlate
      with the degree of hippocampal damage. Continuous 7-week video-EEG monitoring
      after the SE revealed that SRS were expressed in a particular pattern of
      clusters. Taken together, the current study provides an in-depth characterization
      of the mouse pilocarpine model and confirms several features of the
      epileptogenesis process previously reported from the rat pilocarpine model.
      However, the mouse pilocarpine model differs by the rapid onset of seizures and
      an apparent correlation between their numbers and the degree of histopathological
      changes. Our findings highlight that the pilocarpine model of TLE in mice is
      associated with brain pathology akin to different stages of human disease and may
      provide a valuable tool for the discovery of future antiepileptic drugs with
      disease-modifying properties.

PMID- 22960188
TI  - Sulfation modification and anticoagulant activity of the polysaccharides obtained
      from persimmon (Diospyros kaki L.) fruits.
AB  - The optimal conditions for sulfation of polysaccharides from persimmon fruits
      (PFP) with chlorosulfonic acid-pyridine (CSA-Pyr) method were determined by
      response surface methodology. Box-Behnken design was applied to evaluate the
      effects of three independent variables (volume ratio of Pyr to CSA, volume ratio
      of PFP to SO(3)Pyr and reaction time) on the degree of substitution (DS),
      molecular weight (MW) and activated partial thromboplastin time (APTT) of
      sulfated polysaccharides (PFP-S). The APTT activity of PFP-S could be improved by
      application of various volume ratio of Pyr to CSA, volume ratio of PFP to
      SO(3)Pyr and reaction time, which was possible due to the degradation of
      polysaccharides to different extent and increasing of DS. The optimal conditions
      to obtain the strongest APTT of PFP-S were the volume ratio of CSA to Pyr of 1:8,
      the volume ratio of SO(3)Pyr to PFP of 1:3.6 and the reaction time of 3 h,
      respectively.

PMID- 22960189
TI  - Nanofiber scaffolds facilitate functional regeneration of peripheral nerve
      injury.
AB  - Peripheral nerve injury still remains a refractory challenge for both clinical
      and basic researchers. A novel nanofiber conduit made of blood vessel and filled
      with amphiphilic hydrogel of self-assembling nanofiber scaffold (SAPNS) was
      implanted to repair a 10 mm nerve gap after sciatic nerve transection. Empty
      blood vessel conduit was implanted serving as control. Results showed that this
      novel nanofiber conduit enabled the peripheral axons to regenerate across and
      beyond the 10 mm gap. Motoneuron protection, axonal regeneration and
      remyelination were significantly enhanced with SAPNS scaffold treatments. The
      target reinnervation and functional recovery induced by the regenerative nerve
      conduit suggest that SAPNS-based conduit is highly promising application in the
      treatment of peripheral nerve defect. FROM THE CLINICAL EDITOR: In this paper by
      Zhan et al, a novel self-assembling nanofiber scaffold is reported to promote
      regeneration of peripheral nerves in a sciatic nerve injury model. The promising
      results and the obvious medical need raises hope for a clinical translation of
      this approach hopefully in the near future.

PMID- 22960190
TI  - Nanoscale mapping of the Met receptor on hippocampal neurons by AFM and confocal
      microscopy.
AB  - Hepatocyte growth factor (HGF), a neurotrophic protein, acting through its
      tyrosine kinase receptor, Met, facilitates learning and synaptic plasticity. In
      concert with the role of the HGF/Met system in synaptic plasticity, we
      demonstrate that Met is localized to brain regions which undergo extensive
      synaptic remodeling. We demonstrate that Met activation results in an increase in
      dendritic spine density and functional synapses. Based on these observations, we
      hypothesized that Met should be associated with post-synaptic elements found on
      dendritic spines. Thus, the goal of this study was to determine the sub-cellular
      localization of Met on hippocampal neurons. Using an atomic force microscopy tip
      decorated with a specific Met antibody, the location of Met was mapped to
      different cellular compartments of hippocampal pyramidal neurons. Our results
      indicated that multimeric activated Met was found to be concentrated in the
      dendritic compartment while the inactivated monomeric form of Met was prominent
      on the soma. FROM THE CLINICAL EDITOR: The goal of this study was to determine
      the sub-cellular localization of Met on hippocampal neurons using nanotechnology
      based techniques, using an atomic force microscopy tip decorated with a specific
      Met antibody. The authors demonstrate that multimeric activated Met was found to
      be concentrated in the dendritic compartment while the inactivated monomeric form
      of Met was prominent in the soma of hippocampal pyramidal neurons.

PMID- 22960191
TI  - beta-Hydroxybutyric acid grafted solid lipid nanoparticles: a novel strategy to
      improve drug delivery to brain.
AB  - Delivery of drugs to brain is an elusive task in the therapy of many serious
      neurological diseases. With the aim to create a novel formulation to enhance the
      drug uptake to brain, betreliesoxybutyric acid (HBA) grafted docetaxel loaded
      solid lipid nanoparticles (HD-SLNs) were explored. Transportation of HD-SLNs
      relies on the transport of novel ligand, HBA, by monocarboxylic acid transporter
      (MCT1). Expression of MCT1 transporter on brain endothelial cells (bEnd cells)
      was studied using immunocytochemistry. Stearylamine-HBA conjugate was used to
      modify the surface of SLNs and it was confirmed using XPS (X-Ray Photon
      Spectroscopy) analysis. In vitro release studies revealed the controlled release
      of drug from HD-SLNs. Cytotoxicity and cell uptake studies revealed the increased
      uptake of docetaxel with HD-SLNs. Mechanism involved in the uptake of HD-SLNs was
      studied in bEnd cells by saturating MCT1 with excess HBA. Pharmacokinetic and
      brain distribution demonstrated increased docetaxel concentrations in brain
      compared with Taxotere(r). FROM THE CLINICAL EDITOR: The authors of this study
      demonstrate enhanced drug delivery to the brain using a novel formulation of beta
      hydroxybutyric acid grafted docetaxel loaded solid lipid nanoparticles. The
      results show increased uptake of docetaxel compared with Taxotere.

PMID- 22960192
TI  - Excretion and toxicity of gold-iron nanoparticles.
AB  - Though gold nanoparticles have been considered bio-inert, recent studies have
      questioned their safety. To reduce the potential for toxicity, we developed a
      nanoclustering of gold and iron oxide as a nanoparticle (nanorose) which
      biodegrades into subunits to facilitate rapid excretion. In this present study,
      we demonstrate acid and macrophage lysosomal degradation of nanorose via loss of
      the near-infrared optical shift, and clearance of the nanorose in vivo following
      i.v. administration in C57BL/6 mice by showing gold concentration is
      significantly reduced in 11 murine tissues in as little as 31 days (P < 0.01).
      Hematology and chemistry show no toxicity of nanorose injected mice up to 14 days
      after administration. We conclude that the clustering design of nanorose does
      enhance the excretion of these nanoparticles, and that this could be a viable
      strategy to limit the potential toxicity of gold nanoparticles for clinical
      applications. FROM THE CLINICAL EDITOR: The potential toxicity of nanomaterials
      is a critically important limiting factor in their more widespread clinical
      application. Gold nanoparticles have been classically considered bio-inert, but
      recent studies have questioned their safety. The authors of this study have
      developed a clustering gold and iron oxide nanoparticle (nanorose), which
      biodegrades into subunits to facilitate rapid excretion, resulting in reduced
      toxicity.

PMID- 22960193
TI  - EquiNanos: innovative team for nanoparticle risk management.
AB  - Interactions between nanoparticles (NP), humans and the environment are not fully
      understood yet. Moreover, frameworks aiming at protecting human health have not
      been adapted to NP but are nonetheless applied to NP-related activities.
      Consequently, business organizations currently have to deal with NP-related risks
      despite the lack of a proven effective method of risk-management. To respond to
      these concerns and fulfill the needs of populations and industries, EquiNanos was
      created as a largely interdisciplinary provincial research team in Canada.
      EquiNanos consists of eight platforms with different areas of action, from
      adaptive decision-aid tool to public and legal governance, while including
      biological monitoring. EquiNanos resources aim at responding to the concerns of
      the Quebec nanotechnology industry and public health authorities. Our mandate is
      to understand the impact of NP on human health in order to protect the population
      against all potential risks emerging from these high-priority and rapidly
      expanding innovative technologies. FROM THE CLINICAL EDITOR: In this paper by
      Canadian authors an important framework is discussed with the goal of acquiring
      more detailed information and establishing an infrastructure to evaluate the
      interaction between nanoparticles and living organisms, with the ultimate goal of
      safety and risk management of the rapidly growing fields of nanotechnology-based
      biological applications.

PMID- 22960194
TI  - ITO/gold nanoparticle/RGD peptide composites to enhance electrochemical signals
      and proliferation of human neural stem cells.
AB  - A cell chip composed of ITO, gold nanoparticles (GNP) and RGD-MAP-C peptide
      composites was fabricated to enhance the electrochemical signals and
      proliferation of undifferentiated human neural stem cells (HB1.F3). The
      structural characteristics of the fabricated surfaces were confirmed by both
      scanning electron microscopy and surface-enhanced Raman spectroscopy. HB1.F3
      cells were allowed to attach to various composites electrodes in the cell chip
      and the material-dependent effects on electrochemical signals and cell
      proliferation were analyzed. The ITO/60 nm GNP/RGD-MAP-C composite electrode was
      found to be the best material in regards to enhancing the voltammetric signals of
      HB1.F3 cells when exposed to cyclic voltammetry, as well as for increasing cell
      proliferation. Differential pulse voltammetry was performed to evaluate the
      adverse effects of doxorubicin on HB1.F3 cells. In these experiments, negative
      correlations between cell viability and chemical concentrations were obseved,
      which were more sensitive than MTT viability assay especially at low
      concentrations (<0.1 MUg/mL). FROM THE CLINICAL EDITOR: In this basic science
      study, a cell chip composed of ITO, gold nanoparticles and RGD-MAP-C peptide
      composites was fabricated to enhance electrochemical signals and proliferation of
      undifferentiated human neural stem cells (HB1.F3). The ITO/60 nm GNP/RGD-MAP-C
      composite electrode was found to best enhance the voltammetric signals of the
      studied cells.

PMID- 22960195
TI  - Influence of size, surface coating and fine chemical composition on the in vitro
      reactivity and in vivo biodistribution of lipid nanocapsules versus lipid
      nanoemulsions in cancer models.
AB  - Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic
      nanocarriers. Their in vitro and in vivo performance was evaluated as a function
      of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis
      methods included complement activation test, particle uptake in macrophage and
      HEK293(beta3) cells and biodistribution studies with tumor-grafted mice by
      fluorescence imaging. A particular attention was paid to keep the concentration
      of each nanocarrier and to the amount of fluorescent dye in comparable conditions
      between the in vitro and in vivo studies. Under these conditions, no significant
      differences were found among the three tested particle sizes and the two
      nanocarrier types. Longer PEG chains on the LNE surface provided better stealth
      properties, whereas PEG modification on the LNC formulations inhibited the
      production of stable nanocarriers. Passive accumulation of LNCs and LNEs in
      different tumor types depended on the degree of tumor vascularization. FROM THE
      CLINICAL EDITOR: This study of lipid nanocapsules and lipid nanoemulsions
      compares their vitro and in vivo performance as a function of size and surface
      PEG chain length, demonstrating no significant difference among the tested
      particle sizes. Longer PEG chains on the LNE surface provided better stealth
      properties, whereas PEG modification on the LNC formulations inhibited the
      production of stable nanocarriers.

PMID- 22960196
TI  - In vivo effect of glucose-dependent insulinotropic peptide (GIP) on the gene
      expression of calcitonin peptides in human subcutaneous adipose tissue.
AB  - BACKGROUND: Increased plasma levels of calcitonin gene-related peptide-I (CGRP-I)
      and procalcitonin (Pro-CT) (both also named calcitonin peptides (CT peptides))
      are associated with obesity and systemic inflammation. Glucose-dependent
      insulinotropic polypeptide (GIP), a nutrient-dependent incretin hormone, was
      recently found to induce CGRP-I and CT expression in human adipocytes in vitro.
      However, a physiological relevance of a possible interaction between GIP and CT
      peptides has not yet been studied. METHODS: In this study, we analyzed the effect
      of GIP on the expression of CGRP-I and CT mRNA in human subcutaneous adipose
      tissue within a randomized, controlled trial. Seventeen male obese subjects were
      infused with GIP [2.0 pmol kg(-1) min(-1) for 240 min] or placebo, either in the
      fasting state, during euglycemic-hyperinsulinemic (EC) or hyperglycemic
      hyperinsulinemic clamps (HC). RESULTS: The CGRP-I gene expression was detected in
      all investigated adipose tissue samples, whereas very low CT expression was found
      in only 8 out of 116 analyzed samples. No significant influence of either GIP or
      glucose and insulin infusions on the CGRP-I and CT expression was observed in any
      of the individual experiments (GIP infusion, EC and HC) or in the combined
      analysis of all experiments with and without GIP. Furthermore, CGRP-I expression
      was not correlated with plasma GIP level before or after 240 min of infusions or
      clamps. CONCLUSION: In contrast to in vitro data, an acute application of GIP has
      no effect on mRNA expression of CT peptides in subcutaneous adipose tissue of
      obese humans.

PMID- 22960197
TI  - Analysis of Ig gene hypermutation in Ung(-/-)Polh(-/-) mice suggests that UNG and
      A:T mutagenesis pathway target different U:G lesions.
AB  - The activation-induced cytidine deaminase (AID) initiates Ig gene hypermutation
      by converting cytosine to uracil (U) and generating a U:G lesion. Genetic and
      biochemical studies suggest that the AID-triggered U:G lesions are processed by
      three mutagenic pathways to induce mutations at both C:G and A:T pairs. First,
      direct replication of the U:G lesion leads to C to T and G to A transitions.
      Second, U can be excised by the uracil DNA glycosylase (UNG) and the
      replication/processing of the resulting abasic site leads to transversions and
      transitions at C:G pairs. Third, the U:G lesion is recognized by an atypical
      mismatch repair (MMR) pathway which generates mutations at A:T pairs in a DNA
      polymerase eta (POLH)-dependent manner. To further explore whether these three
      mutagenic pathways function competitively or independently, we have analyzed Ig
      gene hypermutation in mice deficient in both UNG and POLH. Compared with WT mice,
      UNG deficiency caused elevated frequency of C:G mutations, suggesting that UNG
      mediated U excision led to error-free as well as error-prone repair. In contrast,
      UNG deficiency did not affect the frequency and patterns of A:T mutations,
      suggesting that the MMR did not target U:G lesions normally recognized and
      processed by UNG. In addition, POLH deficiency did not affect the frequency and
      patterns of C:G mutations and UNG POLH double deficiency showed an additive
      effect of single deficiency. Based on these observations and previous results,
      along with the recent finding that UNG excises AID-triggered U predominantly
      during G1 phase of the cell cycle, it appears that UNG and MMR targets U:G
      lesions generated during G1 and S phases of the cell cycle, respectively.

PMID- 22960198
TI  - Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion
      under hypoxia by increasing MMP2 and MMP9 expression through NF-kappaB/HIF-1alpha
      pathway.
AB  - Both hypoxia and interleukin-17A (IL-17A) promote the migration and invasion of
      fibroblast-like synoviocytes (FLSs), which are critical for the pathogenesis of
      rheumatoid arthritis (RA). However, the biochemical pathways regulating IL-17A
      combined with hypoxia are not well defined. In this study, we found that co
      stimulating RA-FLSs with IL-17A and hypoxia did not appear to promote the
      epithelial-mesenchymal transition (EMT), but did increase cell motility. We
      further showed that a proinvasive effect of IL-17A on FLSs under hypoxia might be
      through upregulation of matrix metalloproteinase 2 (MMP2) and MMP9. Moreover, IL
      17A-induced expression of MMP2 and MMP9 under hypoxia was accompanied by
      increased activation of nuclear factor-kappaB (NF-kappaB)/hypoxia-inducible
      factor-1alpha (HIF-1alpha). Knockdown or inhibition of HIF-1alpha and NF-kappaB
      by small interfering RNA or specific small molecule inhibitors blocked IL-17A
      mediated and hypoxia-mediated MMP2 and MMP9 expression, cell migration, and
      invasion. In addition, the inhibition of NF-kappaB led to a marked decrease in
      the expression of HIF-1alpha, which indicated that IL-17A activated HIF-1alpha
      via the NF-kappaB pathway in hypoxia. Taken together, our observations suggest a
      synergetic effect of IL-17A and hypoxia that might contribute to the migration
      and invasion of RA-FLSs by upregulating the expression of MMP2 and MMP9 by
      activation of the NF-kappaB/HIF-1alpha pathway.

PMID- 22960199
TI  - An optimized method for elution of enteroviral RNA from a cellulose-based
      substrate.
AB  - The Flinders Technology Australia (FTA) Elute Card is a commercial product that
      facilitates the collection, transport, archiving and processing of nucleic acids
      from a wide variety of biological samples at room temperature. While the cards
      have been designed so that sterile/deionized water can elute DNA easily, they are
      not suitable for some less stable RNAs. This study was undertaken to determine
      the optimal conditions such as the buffer type, buffer pH and incubation
      temperature for the elution of enteroviral RNA from FTA Elute Cards prior to
      quantitative analysis using real-time PCR (qPCR) or consensus degenerate hybrid
      oligonucleotide primer VP1 RT-semi nested PCR (CODEHOP VP1 RT-snPCR). TE-1 (pH
      8.0), rather than sterile water, was the best buffer for high efficiency elution
      of enteroviral RNA at 95 degrees C. However, as the estimated recovery rate of
      viral RNA eluted from the cards averaged to be only 6.1%, enterovirus assays
      using FTA elution should be considered qualitative, especially at low virus
      titers, and therefore the results of the assay should be interpreted carefully.

PMID- 22960200
TI  - The effects of electrical stimulation on neurite outgrowth of goldfish retinal
      explants.
AB  - The central nervous system (CNS) in adult mammals loses the ability to regenerate
      after injury. Although electrical stimulation (ES) has been shown to promote
      neural regeneration, the underlying mechanisms by which ES enhances CNS
      regeneration remain elusive. The aim of the present study was to investigate the
      effect of ES on neurite outgrowth of goldfish retinal explants. The optic nerve
      of adult goldfish was intraorbitally crushed 7-14 days before retinal explants
      preparation. The explants were cultured in a laminin-coated indium tin oxide
      (ITO, transparent conducting oxide) device for ES application. Various strengths
      and waveforms of ES were applied to examine their effect on neural outgrowth.
      When the retinal explants were stimulated for 1h with intermittent pulses on day
      1 (20 Hz; 10 pulses every 2s), the regenerated neurite length was significantly
      increased compared to explants that were stimulated with continuous square waves
      or continuous pulses over the same time course. It was also found that increased
      ES strength and repeated ES each day can enhance neurite outgrowth significantly.
      These results suggest that intermittent pulse ES is able to promote neurite
      regeneration most effectively in goldfish retinal explants, and that this
      electrically stimulated neurite outgrowth using ITO conductive electrodes may
      provide a useful platform for investigating cellular mechanisms of CNS
      regeneration.

PMID- 22960201
TI  - Unconscious effects of grammatical gender during object categorisation.
AB  - Does language modulate perception and categorisation of everyday objects? Here,
      we approach this question from the perspective of grammatical gender in
      bilinguals. We tested Spanish-English bilinguals and control native speakers of
      English in a semantic categorisation task on triplets of pictures in an all-in
      English context while measuring event-related brain potentials (ERPs).
      Participants were asked to press a button when the third picture of a triplet
      belonged to the same semantic category as the first two, and another button when
      it belonged to a different category. Unbeknownst to them, in half of the trials,
      the gender of the third picture name in Spanish had the same gender as that of
      the first two, and the opposite gender in the other half. We found no priming in
      behavioural results of either semantic relatedness or gender consistency. In
      contrast, ERPs revealed not only the expected semantic priming effect in both
      groups, but also a negative modulation by gender inconsistency in Spanish-English
      bilinguals, exclusively. These results provide evidence for spontaneous and
      unconscious access to grammatical gender in participants functioning in a context
      requiring no access to such information, thereby providing support for linguistic
      relativity effects in the grammatical domain.

PMID- 22960202
TI  - Expression of the c-fos-monomeric red fluorescent protein 1 fusion gene in the
      spinal cord and the hypothalamic paraventricular nucleus in transgenic rats after
      nociceptive stimulation.
AB  - We generated transgenic rats expressing the c-fos and monomeric red fluorescent
      protein 1 (mRFP1) fusion gene in the central nervous system after adequate
      stimulation. In the present study, the time-course of the induction patterns of
      mRFP1 fluorescence in the spinal cord and the paraventricular nucleus (PVN) was
      compared with that of Fos-like immunoreactivity (LI) within 24 h after
      subcutaneous (s.c.) injection of 0.9% saline and 5% formalin in both hind paws.
      Control rats were not treated. In the control and saline/formalin injected rats,
      scattered mRFP1 fluorescence in the spinal cord and the PVN was observed at 0
      min, though there was little Fos-LI in the same region. The mRFP1 fluorescence in
      the spinal cord and the PVN was increased at 3h after formalin. On the other
      hand, the changes of Fos-LI in the spinal cord and the PVN were relatively
      shorter than those of the mRFP1 fluorescence after formalin. These results
      suggest that the c-fos-mRFP1 fusion gene expression is slightly upregulated in
      normal conditions and nociceptive stimulation-induced induction of the fusion
      gene may be maintained longer than the endogenous c-fos gene expression in the
      spinal cord and the PVN. Next, nocifensive behavior and mRFP1 fluorescence and
      Fos-LI in the spinal cord and the PVN after s.c. injection of formalin, 4alpha
      phorbol 12,13-didecanoate (4alpha-PDD) and saline were compared. Although the
      4alpha-PDD injected rats seldom displayed nocifensive behaviors like s.c. saline
      injection, 4alpha-PDD injection caused mRFP1 fluorescence and Fos-LI
      significantly in the spinal cord and the PVN unlike s.c. saline injection.

PMID- 22960203
TI  - Sound symbolism in infancy: evidence for sound-shape cross-modal correspondences
      in 4-month-olds.
AB  - Perceptual experiences in one modality are often dependent on activity from other
      sensory modalities. These cross-modal correspondences are also evident in
      language. Adults and toddlers spontaneously and consistently map particular words
      (e.g., 'kiki') to particular shapes (e.g., angular shapes). However, the origins
      of these systematic mappings are unknown. Because adults and toddlers have had
      significant experience with the language mappings that exist in their
      environment, it is unclear whether the pairings are the result of language
      exposure or the product of an initial proclivity. We examined whether 4-month-old
      infants make the same sound-shape mappings as adults and toddlers. Four month
      olds consistently distinguished between congruent and incongruent sound-shape
      mappings in a looking time task (Experiment 1). Furthermore, mapping was based on
      the combination of consonants and vowels in the words given that neither
      consonants (Experiment 2) nor vowels (Experiment 3) alone sufficed for mapping.
      Finally, we confirmed that adults also made systematic sound-shape mappings
      (Experiment 4); however, for adults, vowels or consonants alone sufficed. These
      results suggest that some sound-shape mappings precede language learning, and may
      in fact aid in language learning by establishing a basis for matching labels to
      referents and narrowing the hypothesis space for young infants.

PMID- 22960204
TI  - Extremely high myoglobin plasma concentrations producing hook effect in a
      critically ill patient.
AB  - BACKGROUND: A 21-year old female suffered a cardiac arrest after a one week
      history of viral illness later shown to be caused by influenza B. The patient
      required extended cardiopulmonary resuscitation and had further complications
      including compartment syndrome. METHODS: Plasma myoglobin concentration was
      measured using the Roche Diagnostics electrochemiluminescent myoglobin assay.
      RESULTS: The myoglobin concentration was 205,590 MUg/l in an undiluted specimen,
      consistent with severe rhabdomyolysis. Subsequent myoglobin concentrations
      measured two days later showed dramatic decreases to approximately 1000 MUg/l,
      raising suspicion of a hook effect. Dilution and re-analysis of the specimens
      revealed that the actual myoglobin concentrations were >395,000 MUg/l, with one
      specimen possessing an estimated myoglobin concentration of >600,000 MUg/l.
      Interestingly, three specimens from this patient did not show evidence of hook
      effect, with undiluted specimens producing myoglobin concentrations as high as
      284,000 MUg/l. Retrospective analysis of myoglobin results over an 8-year period
      did not reveal other cases with suspicion of hook effect. The case patient had
      the highest myoglobin concentrations out of 7301 specimens. CONCLUSIONS: This
      case illustrates that while the Roche myoglobin assay has a very wide dynamic
      range, hook effect can occur with extremely high concentrations of plasma
      myoglobin.

PMID- 22960205
TI  - Oxysterols modulate calcium signalling in the A7r5 aortic smooth muscle cell
      line.
AB  - Prolonged exposure to oxidized low density lipoprotein (oxLDL) can alter various
      aspects of cell biology, including modification of vasomotor responses and
      downregulation of calcium channel proteins in aortic smooth muscle cells.
      However, the components of oxLDL responsible for these effects have not been
      fully elucidated. The study reported here aimed at examining the consequences of
      extended exposure to oxysterols, cholesterol oxidation products whose levels are
      elevated in oxLDL as compared to unmodified LDL, on calcium signalling mechanisms
      in A7r5 cells, a model aortic smooth muscle cell-line. Within 24 h of exposure,
      all three oxysterol congeners tested caused an elevation in the resting
      cytoplasmic Ca(2+) concentration. These oxysterols also inhibited Ca(2+)
      transients in response to arginine vasopressin and bradykinin, and some but not
      all congeners ablated Ca(2+) signals triggered by platelet activating factor, the
      ryanodine receptor calcium channel agonist 4-choloro-meta-cresol, or
      thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+) uptake. The effects of
      long-term exposure to the oxysterol congener 7beta-hydroxycholesterol on arginine
      vasopressin stimulated Ca(2+) signals were mainly at the level of Ca(2+) release
      from intracellular stores rather than on Ca(2+) influx mechanisms. Of the calcium
      signalling proteins tested, only the type 1 ryanodine receptor and the type 1
      inositol 1,4,5-trisphosphate receptor (IP(3)R1) were significantly downregulated
      by 24 h exposure to oxysterols. Decreases in IP(3)R1 protein triggered by 7beta
      hydroxycholesterol were both time and concentration dependent, occurring over a
      concentration range encountered within atherosclerotic lesions. IP(3)R1
      downregulation by certain oxysterols is mediated by proteasomal proteolysis,
      since it can be abolished by co-incubation with epoxomicin. Overall, these data
      demonstrate that major oxysterol components of oxLDL cause long-term alterations
      in Ca(2+) signalling in a model aortic smooth muscle cell. Such effects could
      contribute to the pathology of atherosclerotic disease.

PMID- 22960206
TI  - Novel animal papillomavirus sequences and accurate phylogenetic placement.
AB  - All amniotes are probably infected by specific papillomaviruses (PVs), but
      knowledge about PV diversity remains sparse. An insufficient taxon sampling, and
      a focus on humans as hosts, may perturb phylogenetic analyses leading to wrong
      conclusions about PV evolution. We performed a systematic approach to explore the
      diversity of PVs combining rolling circle amplification with the use of
      "universal" primers to search for the presence of novel PV sequences in animal
      samples. We communicate 12 sequences putatively corresponding to novel PVs gained
      from 10 host species in eight mammal families: Bovidae, Canidae, Cervidae,
      Equidae, Hominidae, Phocoenidae, Procyonidae and Pteropodidae. The phylogenetic
      position of the new sequences was inferred with an evolutionary placement
      algorithm under a Maximum Likelihood framework using a pre-computed, well
      resolved tree constructed with the E1-E2-L1 gene sequences as a backbone. The new
      sequences were phylogenetically diverse and could be respectively placed with
      confidence within all four PV crown groups. The prevailing presence of sequences
      from the crown groups Alpha+Omikron-PVs and Beta+Xi-PVs may correspond to an
      increased viral diversity in these taxa, or rather reflect a combination of
      anthropocentric bias and preferential amplification from commonly used
      "universal" primers. Our results combined with literature data support the view
      that the number and diversity of animal PVs is overwhelmingly large.

PMID- 22960207
TI  - Synthesis and cytotoxicity of some D-mannose click conjugates with aminobenzoic
      acid derivatives.
AB  - Two sets of new conjugates obtained from d-mannose derivatives and o-, m-, and p
      substituted benzoic acid esters interconnected through a triazole ring were
      synthesized by Cu(I) catalyzed azide-alkyne cycloaddition. All synthesized
      compounds were tested for their in vitro cytotoxic activity against seven cancer
      cell lines with/without multidrug resistance phenotype as well as non-tumor MRC-5
      and BJ fibroblasts. Butyl ester of 4-aminobenzoic acid 6c showed the highest
      activity among all tested compounds, however, it was active only against K562
      myeloid leukemia cells. N-Glycosyltriazole conjugates, both acetylated and
      nonacetylated at mannose moiety, were almost completely inactive. In contrast,
      some of the acetylated O-glycosyl conjugates showed cytotoxic activity which was
      cell line dependent and strongly affected by position of benzoic acid
      substitution as well as a length of its ester alkyl chain; the most potent
      compound was acetylated mannoside conjugated with octyl ester of m-substituted
      benzoic acid. However, deacetylation resulting in hydrophilicity increase of the
      glycosides almost completely abolished their cytotoxic potency.

PMID- 22960208
TI  - Studies on the formation of methylglyoxal from dihydroxyacetone in Manuka
      (Leptospermum scoparium) honey.
AB  - Dihydroxyacetone (DHA) and methylglyoxal (MGO) are unique carbohydrate
      metabolites of manuka honey. A method for the reliable quantification of DHA in
      honey samples was established, based on derivatization with o-phenylenediamine
      (OPD) and subsequent RP-HPLC with UV detection. The previously unknown reaction
      product of DHA and OPD was identified as 2-hydroxymethylquinoxaline by
      spectroscopic means. DHA was exclusively determined in 6 fresh manuka honeys
      originating directly from the beehive as well as 18 commercial manuka honey
      samples, ranging from 600 to 2700 mg/kg and 130 to 1600 mg/kg, respectively. The
      corresponding MGO contents varied from 50 to 250 mg/kg in fresh and 70 to 700
      mg/kg in commercial manuka honey samples. A good linear correlation between DHA
      and MGO values in commercial manuka honeys was observed, resulting in a mean
      ratio of DHA to MGO of 2:1. In contrast to this, the DHA-to-MGO relation was much
      higher in fresh manuka honeys but approximated to a ratio of 2:1 while honey
      ripening. Heating experiments revealed that MGO formation based on thermal
      treatment as a consequence, for example, of caramelization in honey does not
      occur. DHA and MGO can serve as suitable unique quality parameter for manuka
      honey.

PMID- 22960209
TI  - Sugar-metal ion interactions: the coordination behaviors of lanthanum with
      erythritol.
AB  - Three novel lanthanum chloride-erythritol complexes (LaCl(3).C(4)H(10)O(4).5H(2)O
      (LaE(I)), LaCl(3).C(4)H(10)O(4).3H(2)O (LaE(II)), and LaCl(3).1.5C(4)H(10)O(4)
      (LaE(III)) were synthesized and characterized by single crystal X-ray
      diffraction, FTIR, far-IR, THz, and Raman spectroscopy. The coordination number
      of La(3+) is nine. LaE(I) and LaE(II) have similar coordination spheres, but
      their hydrogen bond networks are different. Erythritol exhibits two coordination
      modes: two bidentate ligands and tridentate ligands in LaE(III). Chloride ions
      and water coordinate with La(3+) or participate in the hydrogen-bond networks in
      the three complexes. Crystal structures, FTIR, FIR, THz, and Raman spectra
      provide detailed information on the structures and coordination of hydroxyl
      groups to metal ions in the metal-carbohydrate complexes.

PMID- 22960210
TI  - New steroidal saponins from the bulbs of Lilium brownii var. viridulum.
AB  - Phytochemical investigation of the bulbs of Lilium brownii var. viridulum led to
      the isolation of seven new steroidal saponins (1-7), along with eight known
      analogues (8-15). The new steroidal saponins were identified as 27-O-[(3S)-3-O
      beta-D-glucopyranosyl 3-methylglutaroyl]isonarthogenin 3-O-[alpha-L
      rhamnopyranosyl-(1->2)]-beta-D-glucopyranoside (1), (24S,25S)-3beta,17alpha,24
      trihydroxy-5alpha-spirostan-6-one 3-O-[alpha-L-rhamnopyranosyl-(1->2)]-beta-D
      glucopyranoside (2), tenuifoliol 3-O-[beta-D-glucopyranosyl-(1->4)]-beta-D
      glucopyranoside (3), 26-O-beta-D-glucopyranosylnuatigenin (4), 26-O-beta-D
      glucopyranosylnuatigenin 3-O-beta-D-glucopyranoside (5), 26-O-beta-D
      glucopyranosylnuatigenin 3-O-{alpha-L-rhamnopyranosyl-(1->2)-[beta-D
      glucopyranosyl-(1->6)]}-beta-D-glucopyranoside (6), 26-O-[beta-D-glucopyranosyl
      (1->2)]-beta-D-glucopyranosylnuatigenin 3-O-[alpha-L-rhamnopyranosyl-(1->2)]-beta
      D-glucopyranoside (7), using a combination of spectroscopic evidence and chemical
      methods. The carbohydrate chain of a sugar linked to C-3 of the HMG group (3
      hydroxy-3-methylglutarate) in compound 1 is rarely found in nature. Compound 2
      possesses a new (24S,25S)-3beta,17alpha,24-trihydroxy-5alpha-spirostan-6-one
      aglycon moiety. The disaccharide chain linked to C-26 hydroxy group of the
      furospirostanol in compound 7 has not been observed from natural sources.

PMID- 22960211
TI  - Structure of the O-polysaccharide of Providencia alcalifaciens O3 containing 3,6
      dideoxy-3-formamido-D-glucose and D-galacturonamide.
AB  - Mild acid degradation of the lipopolysaccharide (LPS) of Providencia
      alcalifaciens O3 followed by GPC on Sephadex G-50 and anion-exchange
      chromatography on DEAE-Trisacryl M afforded neutral and acidic polysaccharides,
      LPS core oligosaccharide, and an oligosaccharide composed of one repeat of the
      neutral polysaccharide (O-unit) linked to the LPS core. The following structure
      of the pentasaccharide O-unit was established by sugar and methylation analyses,
      2D (1)H and (13)C NMR spectroscopy and ESI MS: [formula: see text] where Qui3NFo
      stands for 3,6-dideoxy-3-formamidoglucose and GalAN for galacturonamide. The LPS
      core is represented by the Glc(3)Gal(1)GalA(1)Hep(3)Kdo(1)Ara4N(1)P(3)EtN(2)
      glycoform reported earlier for P. alcalifaciens O9, O34, and O19. The acidic
      polysaccharide had the same peptidoglycan-like structure as a polysaccharide
      isolated earlier from P. alcalifaciens O24, O38, and O45, and, most likely,
      represents bacterial capsule material.

PMID- 22960212
TI  - Ancient admixture in human history.
AB  - Population mixture is an important process in biology. We present a suite of
      methods for learning about population mixtures, implemented in a software package
      called ADMIXTOOLS, that support formal tests for whether mixture occurred and
      make it possible to infer proportions and dates of mixture. We also describe the
      development of a new single nucleotide polymorphism (SNP) array consisting of
      629,433 sites with clearly documented ascertainment that was specifically
      designed for population genetic analyses and that we genotyped in 934 individuals
      from 53 diverse populations. To illustrate the methods, we give a number of
      examples that provide new insights about the history of human admixture. The most
      striking finding is a clear signal of admixture into northern Europe, with one
      ancestral population related to present-day Basques and Sardinians and the other
      related to present-day populations of northeast Asia and the Americas. This
      likely reflects a history of admixture between Neolithic migrants and the
      indigenous Mesolithic population of Europe, consistent with recent analyses of
      ancient bones from Sweden and the sequencing of the genome of the Tyrolean
      "Iceman."

PMID- 22960213
TI  - Activity-dependent human brain coding/noncoding gene regulatory networks.
AB  - While most gene transcription yields RNA transcripts that code for proteins, a
      sizable proportion of the genome generates RNA transcripts that do not code for
      proteins, but may have important regulatory functions. The brain-derived
      neurotrophic factor (BDNF) gene, a key regulator of neuronal activity, is
      overlapped by a primate-specific, antisense long noncoding RNA (lncRNA) called
      BDNFOS. We demonstrate reciprocal patterns of BDNF and BDNFOS transcription in
      highly active regions of human neocortex removed as a treatment for intractable
      seizures. A genome-wide analysis of activity-dependent coding and noncoding human
      transcription using a custom lncRNA microarray identified 1288 differentially
      expressed lncRNAs, of which 26 had expression profiles that matched activity
      dependent coding genes and an additional 8 were adjacent to or overlapping with
      differentially expressed protein-coding genes. The functions of most of these
      protein-coding partner genes, such as ARC, include long-term potentiation,
      synaptic activity, and memory. The nuclear lncRNAs NEAT1, MALAT1, and RPPH1,
      composing an RNAse P-dependent lncRNA-maturation pathway, were also upregulated.
      As a means to replicate human neuronal activity, repeated depolarization of SY5Y
      cells resulted in sustained CREB activation and produced an inverse pattern of
      BDNF-BDNFOS co-expression that was not achieved with a single depolarization.
      RNAi-mediated knockdown of BDNFOS in human SY5Y cells increased BDNF expression,
      suggesting that BDNFOS directly downregulates BDNF. Temporal expression patterns
      of other lncRNA-messenger RNA pairs validated the effect of chronic neuronal
      activity on the transcriptome and implied various lncRNA regulatory mechanisms.
      lncRNAs, some of which are unique to primates, thus appear to have potentially
      important regulatory roles in activity-dependent human brain plasticity.

PMID- 22960214
TI  - Limited evidence for classic selective sweeps in African populations.
AB  - While hundreds of loci have been identified as reflecting strong-positive
      selection in human populations, connections between candidate loci and specific
      selective pressures often remain obscure. This study investigates broader
      patterns of selection in African populations, which are underrepresented despite
      their potential to offer key insights into human adaptation. We scan for hard
      selective sweeps using several haplotype and allele-frequency statistics with a
      data set of nearly 500,000 genome-wide single-nucleotide polymorphisms in 12
      highly diverged African populations that span a range of environments and
      subsistence strategies. We find that positive selection does not appear to be a
      strong determinant of allele-frequency differentiation among these African
      populations. Haplotype statistics do identify putatively selected regions that
      are shared across African populations. However, as assessed by extensive
      simulations, patterns of haplotype sharing between African populations follow
      neutral expectations and suggest that tails of the empirical distributions
      contain false-positive signals. After highlighting several genomic regions where
      positive selection can be inferred with higher confidence, we use a novel method
      to identify biological functions enriched among populations' empirical tail
      genomic windows, such as immune response in agricultural groups. In general,
      however, it seems that current methods for selection scans are poorly suited to
      populations that, like the African populations in this study, are affected by
      ascertainment bias and have low levels of linkage disequilibrium, possibly old
      selective sweeps, and potentially reduced phasing accuracy. Additionally,
      population history can confound the interpretation of selection statistics,
      suggesting that greater care is needed in attributing broad genetic patterns to
      human adaptation.

PMID- 22960215
TI  - A novel approach for choosing summary statistics in approximate Bayesian
      computation.
AB  - The choice of summary statistics is a crucial step in approximate Bayesian
      computation (ABC). Since statistics are often not sufficient, this choice
      involves a trade-off between loss of information and reduction of dimensionality.
      The latter may increase the efficiency of ABC. Here, we propose an approach for
      choosing summary statistics based on boosting, a technique from the machine
      learning literature. We consider different types of boosting and compare them to
      partial least-squares regression as an alternative. To mitigate the lack of
      sufficiency, we also propose an approach for choosing summary statistics locally,
      in the putative neighborhood of the true parameter value. We study a demographic
      model motivated by the reintroduction of Alpine ibex (Capra ibex) into the Swiss
      Alps. The parameters of interest are the mean and standard deviation across
      microsatellites of the scaled ancestral mutation rate (theta(anc) = 4N(e)u) and
      the proportion of males obtaining access to matings per breeding season (omega).
      By simulation, we assess the properties of the posterior distribution obtained
      with the various methods. According to our criteria, ABC with summary statistics
      chosen locally via boosting with the L(2)-loss performs best. Applying that
      method to the ibex data, we estimate theta(anc)~ 1.288 and find that most of the
      variation across loci of the ancestral mutation rate u is between 7.7 * 10(-4)
      and 3.5 * 10(-3) per locus per generation. The proportion of males with access to
      matings is estimated as omega~ 0.21, which is in good agreement with recent
      independent estimates.

PMID- 22960216
TI  - Immune response and energy metabolism of Chlamys farreri under Vibrio anguillarum
      challenge and high temperature exposure.
AB  - The complex interactions among host, pathogen and environment are believed to be
      the main causes for the mass mortality of cultured scallops during summer period.
      In the present study, the temporal variations of immune and energy parameters of
      Chlamys farreri under Vibrio anguillarum challenge, higher temperature (29
      degrees C) exposure as well as their combined treatment were investigated in
      order to better understand the energetic mechanisms of scallop immune defense.
      After the treatments, the superoxide anion level, the activities of superoxide
      dismutase (SOD) and acid phosphatase, as well as heat shock protein 70 expression
      level in the hemolymph of scallops increased substantially within 48 h. And as
      time progressed, the malondialdehyde content in the serum of scallops in the
      higher temperature treated and the combined stress treated groups were
      significantly increased, while the SOD activity was significantly depressed (96
      h, P<0.05). After 3 h, a significant decline (P<0.05) in glycogen reserves was
      observed in the examined tissues of all the scallops in the bacteria challenged,
      higher temperature treated and the combined stress treated groups. The cellular
      energy allocation (CEA) in the examined tissues dropped considerably when the
      treatments lasted 48 h. There was a significant decline in the CEA and a
      significant increase in the energy consumption in the examined tissues compared
      with other treatments when the scallops were exposed to the combined stress for
      96 h (P<0.05). All the results demonstrated that the antioxidant systems and
      acute phase response system in scallops were not enough to wholly repair
      oxidative damage caused by higher temperature and the combined stress with
      bacteria challenge, and glycogen reserved in relative tissues were mobilized to
      meet the increased energy demands during the process of immune defense. Immune
      defense against the combined stress imposed greater costs on scallop's energy
      expenditure than either stressor alone, and CEA could be a useful tool to
      evaluate energetic allocation. The information provided valuable insights into
      possible mechanisms of scallop mass mortalities during summer period.

PMID- 22960217
TI  - Evolutionary analysis of Antarctic teleost Toll-like receptor 2.
AB  - In the present study we address the investigation of TLR2 evolutionary selection
      in two Antarctic teleosts, Trematomus bernacchii (Nototheniidae) and Chionodraco
      hamatus (Channichthyidae). The nucleotide sequence of TLR2 has been determined in
      both species, encoding 20 leucine-rich repeats (LRRs) in the extracellular region
      and a classical Toll/IL-1R (TIR) domain in the intracellular region. High
      expression level of T. bernacchii TLR2 was found in spleen and skin. Using
      different methods we identified six codons that underwent Darwinian selection
      while 20 were found to be negatively selected. Molecular models of C. hamatus and
      T. bernacchii TLR2 ectodomain as well as of the TIR domain were built by Homology
      Modeling. Molecular Dynamics simulations were performed in water for 15 ns. The
      sites under positive selection were residing on the convex side of the solenoid,
      four out of six were in a 35-residue-long region including the central/N-terminal
      domain boundary: two in the external loop of LRR11 and the other two in the LRR12
      loop. This region has been demonstrated to be the functional site of ligand
      interaction in human TLR2 structure. Antarctic TLR2 models showed more
      flexibility than TLR2 from the temperate species Gasterosteus aculeatus. These
      results suggest that the selective pressure has shaped TLR2 molecule in such a
      way that increased its activity under the peculiar Antarctic environmental
      conditions.

PMID- 22960218
TI  - Amphioxus CaVPT and creatine kinase are crucial immune-related molecules in
      response to bacterial infection and immunization.
AB  - Although a great progress has been made, our understanding of innate immunity is
      incomplete. Here, we hypothesize that the innate immune response to pathogens is
      attributed into a group of functional proteins. The group contains information on
      host status post bacterial entry (infection or immunity) and bacterial species
      (Gram-positive or Gram-negative bacteria). Investigation of the group of proteins
      may result in disclosing of biomarkers identifying the status and species. For
      this regard, differential proteomics approach coupled with the pattern
      recognition methods are used to identify biomarkers from the proteins that being
      specifically regulated during the innate immune response of amphioxus to Gram
      positive and Gram-negative bacteria with live or dead status. Four proteins,
      Calcium vector protein (CaVP), sarcoplasmic calcium-binding protein (SCP), CaVP
      target protein (CaVPT) and creatine kinase (CK), are selected as the key
      biomarkers. Since immunoprotection of CaVP and SCP has been reported, the role of
      CaVPT and CK are further investigated. Gut CaVPT appears in dying amphioxus,
      whereas humoral fluid CK downregulates and gut CK keep no change in animals with
      immunity. The responses are stronger in Gram-negative than Gram-positive
      bacteria. These results indicate that CaVPT, CK, CaVP and SCP are the most
      important biomarkers to uncover amphioxus innate immunity to bacteria, and the
      approach is an efficient way to identify key biomarkers.

PMID- 22960219
TI  - Chicken FTO gene: tissue-specific expression, brain distribution, breed
      difference and effect of fasting.
AB  - Fat mass and obesity-associated (FTO) gene is widely expressed in central and
      peripheral tissues of mammals, and exhibits a range of functions, especially in
      energy balance. However, basic knowledge of FTO in the chicken is lacking.
      Therefore, we studied the tissue distribution, age and breed dependent changes,
      brain localization, as well as the impact of fasting on FTO mRNA expression in
      the chicken. FTO mRNA was expressed in all the tissues studied, and generally,
      with high expression in hypothalamus, liver, visceral fat and cerebellum. However
      it exhibited breed-specific patterns: in broilers, the highest expression was
      seen in the liver, while in layers, hypothalamus and cerebellum showed relatively
      higher FTO mRNA expression. One-week-old broilers expressed markedly higher FTO
      mRNA in liver compared with the layers of the same age (P<0.01), while the breed
      difference was reversed in visceral fat and cerebellum (P<0.05). Compared with
      newly hatched chicks (one week of age), adult layers expressed higher FTO mRNA in
      liver and visceral fat, while adult broilers showed higher expression in
      hypothalamus and cerebellum. In situ hybridization demonstrated distribution of
      FTO mRNA in paraventricularis magnocellularis (PVN), nucleus ventromedialis
      hypothalami (VMN), nucleus lateralis hypothalami (LHy), nucleus dorsomedialis
      hypothalami (DMN) of the hypothalamus and nucleus habenularis medialis (HM) and
      stratum cellulare externum (SCE) of the thalamus. Breed-specific expression of
      FTO mRNA was shown in PVN, but not in VMN, with higher abundance in broilers
      compared to layers. The decrease in FTO mRNA levels after 24h of fasting was seen
      only in VMN of layer chickens. These results may provide some intriguing hints
      for further investigation of FTO function in the chicken.

PMID- 22960220
TI  - Involvement of the prostaglandin D2 signal pathway in retinoid-inducible gene 1
      (RIG1)-mediated suppression of cell invasion in testis cancer cells.
AB  - Retinoid-inducible gene 1 (RIG1), also called tazarotene-induced gene 3, belongs
      to the HREV107 gene family, which contains five members in humans. RIG1 is
      expressed in high levels in well-differentiated tissues, but its expression is
      decreased in cancer tissues and cancer cell lines. We found RIG1 to be highly
      expressed in testicular cells. When RIG1 was expressed in NT2/D1 testicular
      cancer cells, neither cell death nor cell viability was affected. However, RIG1
      significantly inhibited cell migration and invasion in NT2/D1 cells. We found
      that prostaglandin D2 synthase (PTGDS) interacted with RIG1 using yeast two
      hybrid screens. Further, we found PTGDS to be co-localized with RIG1 in NT2/D1
      testis cells. In RIG1-expressing cells, elevated levels of prostaglandin D2
      (PGD2), cAMP, and SRY-related high-mobility group box 9 (SOX9) were observed.
      This indicated that RIG1 can enhance PTGDS activity. Silencing of PTGDS
      expression significantly decreased RIG1-mediated cAMP and PGD2 production.
      Furthermore, silencing of PTGDS or SOX9 alleviated RIG1-mediated suppression of
      migration and invasion. These results suggest that RIG1 will suppress cell
      migration/invasion through the PGD2 signaling pathway. In conclusion, RIG1 can
      interact with PTGDS to enhance its function and to further suppress NT2/D1 cell
      migration and invasion. Our study suggests that RIG1-PGD2 signaling might play an
      important role in cancer cell suppression in the testis.

PMID- 22960221
TI  - T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired
      expression of IL-12 receptor beta2.
AB  - Foxp3(+) regulatory T (Treg) cells limit inflammatory responses and maintain
      immune homeostasis. Although comprised of several phenotypically and functionally
      distinct subsets, the differentiation of specialized Treg cell populations within
      the periphery is poorly characterized. We demonstrate that the development of T
      bet(+) Treg cells that potently inhibit T helper 1 (Th1) cell responses was
      dependent on the transcription factor STAT1 and occurred directly in response to
      interferon-gamma produced by effector T cells. Additionally, delayed induction of
      the IL-12Rbeta2 receptor component after STAT1 activation helped ensure that Treg
      cells do not readily complete STAT4-dependent Th1 cell development and lose their
      ability to suppress effector T cell proliferation. Thus, we define a pathway of
      abortive Th1 cell development that results in the specialization of peripheral
      Treg cells and demonstrate that impaired expression of a single cytokine receptor
      helps maintain Treg cell-suppressive function in the context of inflammatory Th1
      cell responses.

PMID- 22960222
TI  - gammadelta T cells recognize a microbial encoded B cell antigen to initiate a
      rapid antigen-specific interleukin-17 response.
AB  - gammadelta T cells contribute uniquely to immune competence. Nevertheless, how
      they function remains an enigma. It is unclear what most gammadelta T cells
      recognize, what is required for them to mount an immune response, and how the
      gammadelta T cell response is integrated into host immune defense. Here, we
      report that a noted B cell antigen, the algae protein phycoerythrin (PE), is a
      murine and human gammadelta T cell antigen. Employing this specificity, we
      demonstrated that antigen recognition activated naive gammadelta T cells to make
      interleukin-17 and respond to cytokine signals that perpetuate the response. High
      frequencies of antigen-specific gammadelta T cells in naive animals and their
      ability to mount effector response without extensive clonal expansion allow
      gammadelta T cells to initiate a swift, substantial response. These results
      underscore the adaptability of lymphocyte antigen receptors and suggest an
      antigen-driven rapid response in protective immunity prior to the maturation of
      classical adaptive immunity.

PMID- 22960224
TI  - Impacts of florfenicol on marine diatom Skeletonema costatum through
      photosynthesis inhibition and oxidative damages.
AB  - Effects of the phenicol antibiotic, florfenicol (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0
      mg/L), on marine diatom Skeletonema costatum were investigated in this study.
      Florfenicol was found to stimulate algal growth at concentrations of 0.5, 1.0 and
      2.0 mg/L, and significantly inhibit algal growth at >2.0 mg/L. The highest
      inhibition rate was up to 86% at 16.0 mg/L and the IC(50) for 96 h growth was
      5.043 mg/L. The chlorophyll a and effective quantum yield (DeltaF/F(m)(')) were
      significantly inhibited at 6, 24 and 96 h when florfenicol concentrations were
      >=4.0 mg/L. Intracellular reactive oxygen species (ROS) production was enhanced
      significantly over the control when florfenicol concentrations were >=1.0 mg/L at
      6 h with the dose-dependent trends possibly due to the inhibition of
      photosynthesis. Since the membrane is highly prone to ROS attack, overproduction
      of ROS may cause deteriorated integrity and permeability of the cell membrane.
      Consequently, intracellular pH was found to increase with the increases in
      dosage; cell size swelled significantly when alga was exposed to florfenicol
      concentrations up to 8.0 mg/L. These deteriorations finally led to the decrease
      of cell viability as indicated by both fluorescein diacetate (FDA) assay and
      propidium iodide (PI) staining, in which viability was shown to decrease
      significantly at higher doses (4.0, 8.0, 16.0 mg/L). It can be concluded that S.
      costatum was vulnerable to florfenicol.

PMID- 22960225
TI  - Chronic central administration of valproic acid: Increased pro-survival phospho
      proteins and growth cone associated proteins with no behavioral pathology.
AB  - Valproic acid (VPA) is the most widely prescribed antiepileptic drug due to its
      ability to treat a broad spectrum of seizure types. However, potential
      complications of this drug include anticonvulsant polytherapy metabolism, organ
      toxicity and teratogenicity which limit its use in a variety of epilepsy
      patients. Direct delivery of VPA intracerebroventricularly (ICV) could circumvent
      the toxic effects normally seen with the oral route of administration. An
      additional potential benefit would be significantly reduced dosing while
      achieving high brain concentrations. Epileptogenic tissue from patients with
      intractable seizures has shown significant cell death which may be mitigated by
      maximizing cerebral VPA exposure. Here we show ICV administration of VPA
      localized to the periventricular zone increased pro-survival phospho-proteins
      (pAkt(Ser473), pAkt(Thr308), pGSK3beta(Ser9), pErk1/2(Thr202/Tyr204)) and growth
      cone associated proteins (2G13p, GAP43) in a whole animal system. No significant
      changes in DCX, NeuN, synaptotagmin, and synaptophysin were detected. Assessment
      of possible behavioral alterations in rats receiving chronic central infusions of
      VPA was performed with the open field and elevated plus mazes. Neither paradigm
      revealed any detrimental effects of the drug infusion process.

PMID- 22960223
TI  - The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of
      organ-specific antigens.
AB  - Although the proapoptotic BH3-only protein, Bim, is required for deletion of
      autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ
      specific autoimmune disease. To determine whether other BH3-only proteins
      safeguard tolerance in the absence of Bim, we screened mice lacking Bim as well
      as other BH3-only proteins. Most strains showed no additional defects; however,
      mice deficient for both Puma and Bim spontaneously developed autoimmunity in
      multiple organs, and their T cells could transfer organ-specific autoimmunity.
      Puma- and Bim-double-deficient mice had a striking accumulation of mature, single
      positive thymocytes, suggesting an additional defect in thymic deletion was the
      basis for disease. Transgenic mouse models of thymocyte deletion by peripheral
      neoantigens confirmed that the loss of Bim and Puma allowed increased numbers of
      autoreactive thymocytes to escape deletion. Our data show that Puma cooperates
      with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and
      cement the notion that defects in apoptosis alone are sufficient to cause
      autoimmune disease.

PMID- 22960226
TI  - Empiricists are from Venus, modelers are from Mars: Reconciling experimental and
      computational approaches in cognitive neuroscience.
AB  - We describe how computational models can be useful to cognitive and behavioral
      neuroscience, and discuss some guidelines for deciding whether a model is useful.
      We emphasize that because instantiating a cognitive theory as a computational
      model requires specification of an explicit mechanism for the function in
      question, it often produces clear and novel behavioral predictions to guide
      empirical research. However, computational modeling in cognitive and behavioral
      neuroscience remains somewhat rare, perhaps because of misconceptions concerning
      the use of computational models (in particular, connectionist models) in these
      fields. We highlight some common misconceptions, each of which relates to an
      aspect of computational models: the problem space of the model, the level of
      biological organization at which the model is formulated, and the importance (or
      not) of biological plausibility, parsimony, and model parameters. Careful
      consideration of these aspects of a model by empiricists, along with careful
      delineation of them by modelers, may facilitate communication between the two
      disciplines and promote the use of computational models for guiding cognitive and
      behavioral experiments.

PMID- 22960229
TI  - Two new glycosidated coumaramides from Clerodendron cyrtophyllum.
AB  - Two new glycosidated coumaramides clerodendiod A (1) and B (2), together with
      seven known glycosidic compounds were isolated from the branches of Clerodendron
      cyrtophyllum Turcz. Clerodendiod A and B were elucidated as beta-D-glucopyranosyl
      (1->3)-beta-D-glucopyranosyl-(1->3)-[6-O-(E)-p-methoxycinnamoyl]-beta-D
      glucopyranosyl-(1->2)-[4-O-((E)-2-(4-acetamidobutylcarbamoyl)vinyl)-phenyl]-alpha
      L-rhamnopyranoside (1) and 6-O-(E)-p-coumaroyl-beta-D-glucopyranosyl-(1->3)-beta
      D-glucopyranosyl-(1->3)-[6-O-(E)-p-methoxycinnamoyl]-beta-D-glucopyranosyl-(1->2)
      [4-O-((E)-2-(4-acetamidobutylcarbamoyl)vinyl)-phenyl]-alpha-L-rhamnopyranoside
      (2) on the basis of chemical and spectral evidence. The isolated new compound 2
      was assayed for the inhibition of the NF-kappaB pathway and showed potent
      activity in inhibiting NF-kappaB which its IC(50) values was found to be 24.9 nM.

PMID- 22960227
TI  - American Heart Association cardiopulmonary resuscitation quality targets are
      associated with improved arterial blood pressure during pediatric cardiac arrest.
AB  - AIM: To evaluate the association between cardiopulmonary resuscitation (CPR)
      quality and hemodynamic measurements during in-hospital pediatric cardiac arrest.
      We hypothesized that AHA recommended CPR rate and depth targets would be
      associated with systolic blood pressures>=80mmHg and diastolic blood
      pressures>=30mmHg. METHODS: In children and adolescents <18 years of age who
      suffered a cardiac arrest with an invasive arterial catheter in place, a CPR
      monitoring defibrillator collected CPR data which was synchronized to arterial
      blood pressure (BP) tracings. Chest compression (CC) depths were corrected for
      mattress deflection. Generalized least squares regression estimated the
      association between BP and CPR quality, treated as continuous variables. Mixed
      effects logistic regression estimated the association between systolic
      BP>=80mmHg/diastolic BP>=30mmHg and the AHA targets of depth>=38mm and/or
      rate>=100/min. RESULTS: Nine arrests resulted in 4156 CCs. The median mattress
      corrected depth was 32mm (IQR 28-38); median rate was 111CC/min (IQR 103-120).
      AHA depth was achieved in 1090/4156 (26.2%) CCs; rate in 3441 (83.7%). Systolic
      BP>=80mmHg was attained in 2516/4156 (60.5%) compressions; diastolic>=30mmHg in
      2561/4156 (61.6%). A rate>=100/min was associated with systolic BP>=80mmHg (OR
      1.32; CI(95) 1.04, 1.66; p=0.02) and diastolic BP>=30mmHg (OR 2.15; CI(95) 1.65,
      2.80; p<0.001). Exceeding both (rate>=100/min and depth>=38mm) was associated
      with systolic BP>=80mmHg (OR 2.02; CI(95) 1.45, 2.82; p<0.001) and diastolic
      BP>=30mmHg (OR 1.48; CI(95) 1.01, 2.15; p=0.042). CONCLUSIONS: AHA quality
      targets (rate>=100/min and depth>=38mm) were associated with systolic BPs>=80mmHg
      and diastolic BPs>=30mmHg during CPR in children.

PMID- 22960230
TI  - Efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 in a preclinical
      model of adrenocortical carcinoma.
AB  - Adrenocortical cancer is a rare malignancy for which current pharmacological
      therapies are still insufficient. We tested the effect of a novel PI3 kinase -
      mammalian target of rapamycin dual inhibitor (NVP-BEZ235) on proliferation of the
      H295R adrenocortical cancer cell line in vitro and grown as xenografts in
      immunodeficient mice. NVP-BEZ235 was able to significantly inhibit phosporylation
      of Akt kinase and S6 ribosomal protein in H295R cells and to significantly reduce
      their proliferation in vitro and xenograft growth in vivo. The drug also induced
      activation of Erk phosphorylation, which could be inhibited by simultaneous
      treatment with the Erk inhibitor FR180204. This latter drug synergized with NVP
      BEZ235 in the inhibition of H295R proliferation in vitro. Our data suggest that
      dual PI3K/mTOR inhibitors may represent a useful pharmacological tool in the
      therapy of advanced adrenocortical cancer and that simultaneous inhibition of
      both Erk and PI3K - mTOR pathways may be required to obtain a higher
      antiproliferative effect in this type of tumor.

PMID- 22960231
TI  - AU-rich elements in the 3'-UTR regulate the stability of the 141 amino acid
      isoform of parathyroid hormone-related protein mRNA.
AB  - We demonstrated previously that parathyroid hormone-related protein (PTHrP) 1-141
      mRNA is the least stable of three isoforms and is the only isoform that is
      stabilized by TGF-beta. In order to understand how PTHrP mRNA is stabilized by
      TGF-beta, we first sought to elucidate the mechanism(s) that are responsible for
      the instability of PTHrP isoform 1-141 mRNA. The 3'-UTR of isoform 1-141 contains
      four AU-rich elements (AREs), which are known to mediate mRNA degradation. We
      utilized a luciferase reporter system to test whether these four AREs are
      responsible for the short half-life of PTHrP 1-141 mRNA. Our results demonstrated
      that ARE elements in the 3'-UTR of PTHrP 1-141 mRNA play a significant role in
      regulation of the stability of the mRNA. It is known that AREs mediate their
      effects on mRNA stability through a number of ARE-binding proteins that recruit
      the exosome, a complex of exonucleases that degrades the mRNA. We identified
      tristetraproline (TTP) as an RNA-binding protein that may be involved in ARE
      mediated degradation of PTHrP 1-141 mRNA.

PMID- 22960232
TI  - Origin and plasticity of the subdivisions of the inferior olivary complex.
AB  - The precerebellar nuclei (PCN) originate from the rhombic lip, a germinal
      neuroepithelium adjacent to the roof plate of the fourth ventricle. We first
      report here that, in chicken, the Brn3a-expressing postmitotic medullary cells
      that produce the inferior olive (ION, the source of cerebellar climbing fibres)
      originate from a dorso-ventral domain roughly coinciding with the hindbrain
      vestibular column. Whereas Foxd3 expression labels the whole mature ION but is
      only detected in a subpopulation of ION neuroblasts initiating their migration,
      we report that Brn3a allows the visualization of the whole population of ION
      neurons from the very beginning of their migration. We show that Brn3a-positive
      neurons migrate tangentially ventralwards through a characteristic dorso-ventral
      double submarginal stream. Cath1 expressing progenitors lying just dorsal to the
      ION origin correlated dorso-ventral topography with the prospective cochlear
      column (caudal to it) and generate precerebellar nuclei emitting mossy-fiber
      cerebellar afferents. We used the chick-quail chimaera technique with homotopic
      grafts at HH10 to determine the precise fate map of ION precursors across the
      caudal cryptorhombomeric subdivisions of the medullary hindbrain (r8-r11). We
      demonstrate that each crypto-rhombomere contributes to two lamellae of the ION,
      while each ION sub-nucleus originates from at least two contiguous crypto
      rhombomeres. We then questioned how rhombomere identity is related to the
      plasticity of cell type specification in the dorsal hindbrain. The potential
      plasticity of ectopically HH10 grafted ION progenitors to change their original
      fate in alternative rostrocaudal environments was examined. Heterotopic grafts
      from the presumptive ION territory to the pontine region (r4-r5) caused a change
      of fate, since the migrated derivatives adopted a pontine phenotype. The reverse
      experiment caused pontine progenitors to produce derivatives appropriately
      integrated into the ION complex. Grafts of ION progenitor domains to myelomeres
      (my) 2-3 also showed complete fate regulation, reproducing spinal cord-like
      structures, whereas the reverse experiment revealed the inability of my2-3 to
      generate ION cell types. This was not the case with more caudal, relatively less
      specified myelomeres (my5-6). Interestingly, when heterotopically grafted cells
      are integrated dorsally, they do not change their phenotype. Our results support
      the hypothesis that positional information present in the hindbrain and spinal
      cord at early neural tube stages controls the specific fates of ventrally
      migrating PCN precursors.

PMID- 22960233
TI  - DREF is required for cell and organismal growth in Drosophila and functions
      downstream of the nutrition/TOR pathway.
AB  - Nutrient availability is a key determinant of animal growth. The conserved
      insulin/PI3 kinase and TOR kinase signaling pathways are two of the best
      characterized regulators of cell and tissue growth in response to nutritional
      conditions. Studies in Drosophila larvae show that one mechanism by which these
      pathways drive growth is by regulating the expression of metabolic genes,
      especially those genes required for protein synthesis. Here we examine a role for
      the transcription factor DREF in mediating some of these transcriptional and
      growth responses. We find that loss of DREF leads to a decrease in organismal
      growth. These effects are in part due to a requirement for DREF function in cell
      autonomous growth. We also uncover a non-autonomous role for DREF activity in the
      larval fat body. Previous studies show that activation of TOR in the fat body
      couples nutrition to insulin release from the brain; we find that inhibition of
      DREF in the fat body can phenocopy effects of nutrient deprivation and fat
      specific TOR inhibition, leading to a reduction in systemic insulin signaling,
      delayed larval growth and smaller final size. Using genetic epistasis, we find
      that DREF is required for growth downstream of TOR, but not insulin/PI3K
      signaling. Moreover, we show that TOR can control DREF mRNA levels, in part via
      the transcription factor dMyc. Finally we show that DREF is required for normal
      expression of many ribosome biogenesis genes, suggesting that one mechanism by
      which DREF is required for growth is through the control of protein synthetic
      capacity. Together these findings suggest DREF is an essential transcription
      factor in the nutritional control of cell and tissue growth during Drosophila
      development. Given that DREF is conserved, this role may also be important in the
      control of growth in other animals.

PMID- 22960234
TI  - Cdx2 contributes to the expansion of the early primordial germ cell population in
      the mouse.
AB  - Cdx gene products regulate the extent of axial elongation from the posterior
      growth zone. These transcription factors sustain the emergence of trunk and tail
      tissues by providing a suitable niche in the axial progenitor zone, via
      regulation of Wnt signaling. Cdx genes are expressed in and along the complete
      primitive streak including its posterior part wherefrom the extraembryonic
      mesoderm of the allantois emerges. Cdx genes are required for the full
      development of the allantois and its derivatives in the placental labyrinth. The
      mouse germ cell lineage also originates from the proximo-posterior epiblast of
      the primitive streak, and is established within the extraembryonic mesoderm that
      generates the allantois. We asked whether the expression of Cdx genes around the
      newly specified PGCs is necessary for the maintenance and expansion of this
      population, as it is for the allantois and axial progenitors. We observed a
      significantly lower number of PGCs in Cdx2(null) embryos than in controls. We
      found that Wnt3a loss of function decreases the PGC population to the same extent
      as Cdx2 inactivation. Moreover, exogenous Wnt3a corrects the lower PGC number in
      Cdx2(null) posterior embryonic tissues cultured in vitro. Cdx2 is not expressed
      in PGCs themselves, and we propose that the expression of Cdx2 in posterior
      extraembryonic tissues contributes to the proper niche of the germ cell
      progenitors by stimulating canonical Wnt signaling. Since PGC residence within
      the posterior growth zone is a mouse-specific feature, our data suggest that
      mouse PGCs opportunistically became dependent on the axial progenitor niche.

PMID- 22960235
TI  - Loss of Oct4 expression during the development of murine embryoid bodies.
AB  - We describe the internal organization of murine embryoid bodies (EBs) in terms of
      the structures and cell types formed as Oct4 expression becomes progressively
      lost. This is done by making the EBs from iPS cells carrying a novel Oct4
      reporter (Oct4-MerCreMer;mTmG) which is inducible, sensitive, and permanent in
      all cellular progeny. When these EBs are treated with tamoxifen, the Oct4
      expressing cells switch from a red to a green fluorescence color, and this is
      maintained thereafter by all their progeny. We show that there is no specific
      pattern in which Oct4 is downregulated, rather it appears to be spatially random.
      Many of the earliest cells to lose Oct4 expression stain positive for markers of
      visceral endoderm (DAB2, alpha-fetoprotein (AFP), HNF4). These are randomly
      located, although if endoderm differentiation is allowed to commence before EB
      formation then an external layer is formed. This is true both of EBs made from
      the reporter iPS cells, or from an embryo-derived mouse ES line (R1 cells).
      Markers of the early body axis, Brachyury (BRA) and FOXA2, usually showed a
      concentration of positive cells in one region of the EB, but the morphology is
      not predictable and there are also scattered cells expressing these markers.
      These patterns are similar in R1 cells. Use of the Oct4 reporter showed a
      difference between BRA and FOXA2. BRA, which marks the early mesoderm, node and
      notochord, arises in Oct4 expressing cells on days 3-4. FOXA2, which marks the
      floor plate of the neural tube and definitive endoderm, as well as the node and
      notochord, arises at the same time but mostly in cells that have already lost
      Oct4 expression. Several clumps of cardiomyocytes are visible by days 7-8 of EB
      development, both in our iPS cells and in R1 cells. Using the Oct4 reporter we
      show that the cells forming these clumps lose Oct4 expression between days 3 and
      5. Overall, our results indicate that EBs recapitulate normal development quite
      well in terms of the tempo of events and the appearance of specific markers, but
      they do not resemble embryos in terms of their morphology.

PMID- 22960236
TI  - Does oxidized LDL contribute to atherosclerotic plaque formation and
      microvascular complications in patients with type 1 diabetes?
AB  - OBJECTIVE: The aim of the study was to investigate whether changes in the level
      of oxidized LDL (oxLDL) over 2-years contribute to the development of subclinical
      macroangiopathy and/or microvascular complications in patients with DM1. DESIGN
      AND METHODS: Basic clinical and biochemical parameters and oxLDL level were
      measured in 70 patients at baseline and after 2 years of the study. In addition,
      an ultrasonographic study was performed to assess the carotid intima media
      thickness (IMT). RESULTS: Patients did not differ according to basic clinical and
      biochemical parameters at the beginning and after 2 years of the study. IMT
      increased (p=0.000001) whereas oxLDL level decreased (p=0.00001) in DM1 patients
      during 2 years. Multivariate regression analysis showed that oxLDL independently
      influences IMT in DM1 patients (beta=0.454, R2=0.35). Further, positive
      correlations between oxLDL value and LDL-C concentration (r=0.585, p<0.05, n=70)
      and between oxLDL level and apo-B concentration have been established (r=0.610,
      p<0.05, n=70). Moreover, patients with chronic microvascular complications showed
      a higher value of IMT in comparison with patients without them (p=0.003).
      CONCLUSION: Our results provide the evidence that oxLDL accelerates
      atherosclerotic plaque formation and may contribute to the development of
      microvascular complications in DM1.

PMID- 22960237
TI  - Bivariate genome-wide association study suggests fatty acid desaturase genes and
      cadherin DCHS2 for variation of both compressive strength index and appendicular
      lean mass in males.
AB  - Compressive strength index (CSI) is a newly established index for predicting hip
      fracture, the most serious consequence of osteoporosis. Appendicular lean mass
      (ALM), which influences skeletal strength of the lower limbs, is another trait
      associated with the risk of hip fracture. In this study, we performed a bivariate
      genome-wide association study (GWAS) to identify new candidate genes responsible
      for both CSI and ALM. In our discovery sample of 1627 unrelated Chinese subjects
      (802 males and 825 females), we scanned 909,509 SNPs using the Affymetrix Human
      Genome SNP 6.0 genotyping array. We successfully replicated our results in a
      sample of 2286 Caucasian subjects (558 males and 1728 females). The results
      indicated that five SNPs (rs174583, rs174577, rs174549, rs174548, rs7672337) in
      the FADS1, FADS2, and DCHS2 genes had significant bivariate associations with CSI
      and ALM in male subjects for both the GWAS discovery (with P<8.42*10(-6)) and the
      Caucasian sample (with P<0.07). We performed further replication analysis in a
      2nd Caucasian sample with 501 Caucasian male subjects, using Affymetrix 500k
      arrays, and found that two of the above SNPs (rs174548 and rs174549, P=0.07) had
      bivariate associations with both CSI and ALM in males; the other 3 SNPs were not
      typed with the 500k array. The above findings suggest that the 3 genes, FADS1,
      FADS2, and DCHS2, containing these SNPs might play dual roles influencing both
      CSI and ALM in males. Our findings provide new insights into our understanding of
      the genetic basis of bone metabolism and the pathogenesis of osteoporosis.

PMID- 22960238
TI  - beta1 selectivity of beta-blockers and reduced risk of fractures in elderly
      hypertension patients.
AB  - INTRODUCTION: Hypertension and osteoporosis are prevalent in the elderly
      population. Treatments beneficial to both conditions would be helpful. We
      examined the protective effect of beta-blockers (BBs) and their receptor
      selectivity against fractures compared to other antihypertensives. MATERIALS AND
      METHODS: A retrospective cohort was assembled using the Korean Health Insurance
      Review and Assessment Service database from January 2005 to June 2006. The cohort
      consisted of 501,924 patients (ages 65 and older) on single-drug therapy for
      hypertension. Participants were followed to either the date of the first
      fracture, date of death or end of the study period (30 June 2006), whichever came
      first. Cox's proportional hazard model was used to calculate the adjusted hazard
      ratio (aHR) and 95% confidence interval (CI) by sex, adjusting for confounders.
      Risk of fractures by BBs according to beta1 selectivity was compared to non BBs
      measured in aHR. RESULTS: Among 501,924 (65% female), the incidence density of
      fractures in non BB users was 29.3 and 48.2 per 1000 person-years for men and
      women, respectively, which was higher than in BB users (17.2 for men and 30.5 for
      women). Compared to BB users, non BB users showed an increased risk of all
      fracture [aHR 1.56 (95% CI, 1.42-1.72) in men and 1.44 (95% CI, 1.36-1.51) in
      women] and hip fracture [aHR 2.17 (95% CI 1.45-3.24) in men and 1.61 (95% CI 1.31
      1.98) in women] after adjusting for confounding variables. Compared to BBs, the
      risks of all fractures in alpha-blockers, calcium channel blockers, diuretics,
      and renin-angiotensin-aldosterone system blockers were significantly higher
      (1.72, 1.77, 1.58, 1.29 in men; 2.11, 1.50, 1.46, 1.22 in women, respectively).
      Compared to non BBs, beta1 selective BBs showed a lower risk of fracture (39% for
      men and 33% for women) after adjusting for confounding factors. On the contrary,
      non-selective BBs were not protective against fracture. CONCLUSION: Our results
      suggested that beta1 selective BBs reduce the risk of fractures compared to other
      classes of antihypertensives in an elderly population, which could have practical
      applications for strategies to control and prevent adverse outcomes from both
      hypertension and osteoporosis in this population.

PMID- 22960239
TI  - A randomized controlled trial on the efficacy of intermittent and continuous
      traction for patients with knee osteoarthritis.
AB  - OBJECTIVE: To investigate the efficacy of intermittent and continuous traction in
      the treatment of knee osteoarthritis. DESIGN: A randomized, controlled, observer
      blind seven-week trial. SETTING: Hospital-based outpatient practice. SUBJECTS:
      Ninety-eight patients with stage 3 knee osteoarthritis according to Kellgren
      Lawrence radiological rating scale. INTERVENTIONS: All 98 patients were randomly
      assigned to three treatment groups, for three weeks (weekends excluded). The
      control group (n=30, mean age: 59.30+/-8.16) received hot pack and short wave
      diathermy; the intermittent group (n=30, mean age: 58.20+/-7.78) received hot
      pack, short wave diathermy and intermittent traction; and the continuous group
      (n=30, mean age: 57.97+/-9.53) received hot pack, short wave diathermy and
      continuous traction. OUTCOME MEASUREMENTS: The values of the Turkish version of
      the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),
      visual analog scale, and knee passive range of motion were measured at baseline,
      three-week and seven-week follow-up. RESULTS: Compared with baseline at weeks 3
      and 7, all the outcome measures, except range of motion, were significantly
      reduced in all groups (all P<=0.001). In terms of the change data from baseline
      to week 3, both traction groups were significantly superior to the control in the
      WOMAC physical function scores. Considering the change data from baseline to week
      7, both traction groups were significantly superior to the control in the pain
      scores, physical function and total scores, while only the continuous group was
      significantly better than the control in the stiffness scores (control: 1.17 +/-
      1.64; continuous: 2.38 +/- 1.44) (P=0.014). Compared with baseline at weeks 3 and
      7, range of motion values significantly increased in both traction groups
      (P<0.05) but not in the control (P>0.05). However, there were no significant
      differences among the three groups considering the change data from baseline to
      week 7 in range of motion values (P=0.300). CONCLUSIONS: Joint traction was found
      to be beneficial for the improvement of pain and physical function loss related
      to knee osteoarthritis.

PMID- 22960240
TI  - Mirror therapy for patients with severe arm paresis after stroke--a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects of individual or group mirror therapy on
      sensorimotor function, activities of daily living, quality of life and
      visuospatial neglect in patients with a severe arm paresis after stroke. DESIGN:
      Randomized controlled trial. SETTING: Inpatient rehabilitation centre. SUBJECT:
      Sixty patients with a severe paresis of the arm within three months after stroke.
      INTERVENTIONS: Three groups: (1) individual mirror therapy, (2) group mirror
      therapy and (3) control intervention with restricted view on the affected arm.
      MAIN MEASURES: Motor function on impairment (Fugl-Meyer Test) and activity level
      (Action Research Arm Test), independence in activities of daily living (Barthel
      Index), quality of life (Stroke Impact Scale) and visuospatial neglect (Star
      Cancellation Test). RESULTS: After five weeks, no significant group differences
      for motor function were found (P > 0.05). Pre-post differences for the Action
      Research Arm Test and Fugl-Meyer Test: individual mirror therapy: 3.4 (7.1) and
      3.2 (3.8), group mirror therapy: 1.1 (3.1) and 5.1 (10.0) and control therapy:
      2.8 (6.7) and 5.2 (8.7). However, a significant effect on visuospatial neglect
      for patients in the individual mirror therapy compared to control group could be
      shown (P < 0.01). Furthermore, it was possible to integrate a mirror therapy
      group intervention for severely affected patients after stroke. CONCLUSION: This
      study showed no effect on sensorimotor function of the arm, activities of daily
      living and quality of life of mirror therapy compared to a control intervention
      after stroke. However, a positive effect on visuospatial neglect was indicated.

PMID- 22960241
TI  - Validity of the Nintendo Wii(r) balance board for the assessment of standing
      balance in Parkinson's disease.
AB  - BACKGROUND: Impaired postural stability places individuals with Parkinson's at an
      increased risk for falls. Given the high incidence of fall-related injuries
      within this population, ongoing assessment of postural stability is important.
      OBJECTIVE: To evaluate the validity of the Nintendo Wii((r)) balance board as a
      measurement tool for the assessment of postural stability in individuals with
      Parkinson's. SUBJECTS: Twenty individuals with Parkinson's participated.
      INTERVENTION: Subjects completed testing on two balance tasks with eyes open and
      closed on a Wii((r)) balance board and biomechanical force platform. MAIN
      MEASURES: Bland-Altman plots and a two-way, random-effects, single measure
      intraclass correlation coefficient model were used to assess concurrent validity
      of centre-of-pressure data. RESULTS: Concurrent validity was demonstrated to be
      excellent across balance tasks (intraclass correlation coefficients = 0.96, 0.98,
      0.92, 0.94). CONCLUSIONS: This study suggests that the Wii((r)) balance board is
      a valid tool for the quantification of postural stability among individuals with
      Parkinson's.

PMID- 22960242
TI  - Joint STFC Futures/BIR workshop "Cancer care: new detector and sensor
      technologies and their potential impact", Harwell Oxford, 5-6 October 2011.
AB  - The workshop "Cancer care: new detector and sensor technologies and their
      potential impact", organised jointly by the Science and Technology Facilities
      Council (STFC) and the British Institute of Radiology, brought together
      representatives from the cancer community (clinicians, medical physicists,
      National Health Service representatives and general practitioners with an
      interest in cancer) and STFC-supported scientists involved in basic research in
      physics and technology. The workshop aimed to raise awareness of the cancer
      challenge, share knowledge and identify novel solutions in the area of detectors
      and sensors to addressing the cancer challenge. A further aim of this workshop
      was to commence discussion on the formation of new multidisciplinary community
      networks. The workshop identified the synergies between the two communities and
      the potential for developing new collaborative ideas and projects.

PMID- 22960243
TI  - Multiple diagnostic task performance in CT examination of the chest.
AB  - OBJECTIVES: In three experiments, we studied the detection of multiple
      abnormality types using the satisfaction of search (SOS) paradigm, the provision
      of a computer-aided detection (CAD) of pulmonary nodules and a focused nodule
      detection task. METHODS: 51 chest CT examinations (24 that demonstrated subtle
      pulmonary nodules and 27 that demonstrated no pulmonary nodules) were read by 15
      radiology residents and fellows under two experimental conditions: (1) when there
      were no other abnormalities present except test abnormalities in the exams (non
      SOS condition), and (2) when other abnormalities were present in the exams (SOS
      condition). Trials from the two conditions were intermixed. Readers were invited
      to return for two sessions: one in which the SOS condition was repeated with a
      simulated CAD; another in which only the non-SOS condition was presented.
      Detection accuracy was measured using receiver operating characteristic (ROC)
      analysis. RESULTS: An SOS effect (reduced detection accuracy for the test nodules
      in the presence of the diverse added abnormalities) was not found. Average
      accuracy was much higher when the CAD prompt was provided, without cost in the
      detection of the added abnormalities. Accuracy for detecting nodules appearing
      without intermixed SOS trials was also substantially improved. CONCLUSIONS: CT
      interpretation was highly task dependent. Nodule detection was poor in the
      general search task. Therefore, CAD may offer a greater performance improvement
      than demonstrated in experiments assessing CAD using focused search. The absence
      of SOS may be due to limited nodule detection even without other abnormalities.
      Advances in knowledge CAD prompts of nodules increase the detection accuracy of
      nodules and decrease the time to detection-without impairing the detection
      accuracy-of non-nodule abnormalities.

PMID- 22960244
TI  - Skeletal muscle disease: patterns of MRI appearances.
AB  - Although the presumptive diagnosis of skeletal muscle disease (myopathy) may be
      made on the basis of clinical-radiological correlation in many cases, muscle
      biopsy remains the cornerstone of diagnosis. Myopathy is suspected when patients
      complain that the involved muscle is painful and tender, when they experience
      difficulty performing tasks that require muscle strength or when they develop
      various systemic manifestations. Because the cause of musculoskeletal pain may be
      difficult to determine clinically in many cases, MRI is increasingly utilised to
      assess the anatomical location, extent and severity of several pathological
      conditions affecting muscle. Infectious, inflammatory, traumatic, neurological,
      neoplastic and iatrogenic conditions can cause abnormal signal intensity on MRI.
      Although diverse, some diseases have similar MRI appearances, whereas others
      present distinct patterns of signal intensity abnormality. In general,
      alterations in muscle signal intensity fall into one of three cardinal patterns:
      muscle oedema, fatty infiltration and mass lesion. Because some of the muscular
      disorders may require medical or surgical treatment, correct diagnosis is
      essential. In this regard, MRI features, when correlated with clinical and
      laboratory findings as well as findings from other methods such as
      electromyography, may facilitate correct diagnosis. This article will review and
      illustrate the spectrum of MRI appearances in several primary and systemic
      disorders affecting muscle, both common and uncommon. The aim of this article is
      to provide radiologists and clinicians with a collective, yet succinct and
      useful, guide to a wide array of myopathies.

PMID- 22960245
TI  - Priapism: pathophysiology and the role of the radiologist.
AB  - Priapism is defined as a penile erection that persists for 4 h or longer and is
      unrelated to sexual activity. Its identification is important as lack of timely
      treatment (particularly of the low flow/ischaemic subgroup) can result in
      persisting erectile dysfunction as a consequence of irreversible corporal
      fibrosis. This review describes the physiology and anatomy of the normal
      erection, the aetiology and pathophysiology of the different types of priapism,
      and the role of the radiologist in the management of the condition. The treatment
      of iatrogenic priapism following intracavernosal injection of pharmacostimulant
      is discussed.

PMID- 22960246
TI  - Control of tiller growth of rice by OsSPL14 and Strigolactones, which work in two
      independent pathways.
AB  - The architecture of rice is greatly influenced by the growth of tillers, i.e.
      vegetative shoot branches. OsSPL14, a member of the SQUAMOSA PROMOTER BINDING
      PROTEIN-LIKE (SPL) genes, and strigolactones (SLs) are known to suppress
      outgrowth of tiller buds. OsSPL14 also regulates panicle development. We show
      that OsSPL14 mRNA accumulates in leaf primordia during the vegetative phase and
      in the primordia of bracts, or modified leaves, in the panicles, but not in the
      meristems. OsSPL14 is a target of miR156, and accumulation of OsSPL14 transcripts
      is negatively regulated by miR156. The enhancement of the expression level of
      OsSPL14 by the introduction of the mOsSPL14 gene, in which the miR156 cleavage
      site is mutated, resulted in an increase in the plastochron, an acceleration of
      flowering and a decrease in tiller number in the wild type and in dwarf10-2, an
      SL-deficient mutant. Our analysis suggests that OsSPL14 and SLs function in
      parallel pathways to suppress tiller growth. SLs exuded from roots trigger
      germination of root parasitic plants that can cause severe damage to crop
      productivity. SL-deficient mutants, however, exhibit an excess branching
      phenotype which is usually undesirable for productivity. Our results indicate
      that OsSPL14 can be used to manipulate the branching patterns of SL-deficient
      mutants. We also confirmed that this strategy is applicable to Arabidopsis. A
      greater understanding of the OsSPL14 and SL pathways and their interactions may
      help in the production of root parasite-resistant crops.

PMID- 22960247
TI  - The E3 ubiquitin ligase HOS1 regulates low ambient temperature-responsive
      flowering in Arabidopsis thaliana.
AB  - Ubiquitin-dependent proteolysis regulates multiple aspects of plant growth and
      development, but little is known about its role in ambient temperature-responsive
      flowering. In addition to being regulated by daylength, the onset of flowering in
      many plants can also be delayed by low ambient temperatures. Here, we show that
      HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1), which encodes an E3
      ubiquitin ligase, controls flowering time in response to ambient temperatures (16
      and 23 degrees C) and intermittent cold. hos1 mutants flowered early, and were
      insensitive to ambient temperature, but responded normally to vernalization and
      gibberellic acid. Genetic analyses suggested that this ambient temperature
      insensitive flowering was independent of FLOWERING LOCUS C (FLC). Also, FLOWERING
      LOCUS T (FT) and TWIN SISTER OF FT (TSF) expression was up-regulated in hos1
      mutants at both temperatures. The ft tsf mutation almost completely suppressed
      the early flowering of hos1 mutants at different temperatures, suggesting that FT
      and TSF are downstream of HOS1 in the ambient temperature response. A lesion in
      CONSTANS (CO) did not affect the ambient temperature-insensitive flowering
      phenotype of hos1-3 mutants. In silico analysis showed that FVE was
      spatiotemporally co-expressed with HOS1. A HOS1-green fluorescent protein (GFP)
      fusion co-localized with FVE-GFP in the nucleus at both 16 and 23 degrees C. HOS1
      physically interacted with FVE and FLK in yeast two-hybrid and co
      immunoprecipitation assays. Moreover, hos1 mutants were insensitive to
      intermittent cold. Collectively, our results suggest that HOS1 acts as a common
      regulator in the signaling pathways that control flowering time in response to
      low ambient temperature.

PMID- 22960248
TI  - Representation of possible and impossible objects in the human visual cortex:
      evidence from fMRI adaptation.
AB  - Impossible objects are defined as 2D drawings that represent objects that could
      not exist in real 3D space. Previous studies have proposed that such objects are
      represented differently in long-term memory due to their invalid spatial
      structure. Nevertheless, it is not clear whether these discrepancies reflect
      early perceptual processes or late, post-recognition, processes. Here, we address
      this issue by using fMRI adaptation. Interestingly, equivalent adaptation levels
      were obtained for repeated compared to non-repeated possible and impossible
      objects in object selective regions within the human high-level visual cortex.
      Yet, a significant correlation between fMRI adaptation and behavioral
      facilitation was found for possible but not for impossible objects, thus
      exhibiting some dissociation in the representation of the two object categories.
      Overall, our findings suggest that the initial perception of possible and
      impossible objects is mediated by shared neural mechanisms whereas the observed
      differences between the two types of objects may reflect higher post-recognition
      processes.

PMID- 22960249
TI  - Subthalamic nucleus gamma oscillations mediate a switch from automatic to
      controlled processing: a study of random number generation in Parkinson's
      disease.
AB  - In paced random number generation (RNG) participants are asked to generate
      numbers between 1 and 9 in a random fashion, in synchrony with a pacing stimulus.
      Successful task performance can be achieved through control of the main biases
      known to exist in human RNG compared to a computer generated series: seriation,
      cycling through a set of available numbers, and repetition avoidance. A role in
      response inhibition and switching from automatic to controlled processing has
      previously been ascribed to the subthalamic nucleus (STN). We sought evidence of
      frequency-specific changes in STN oscillatory activity which could be directly
      related to use of such strategies during RNG. Local field potentials (LFPs) were
      recorded from depth electrodes implanted in the STN of 7 patients (14 sides) with
      Parkinson's disease (PD), when patients were on dopaminergic medication. Patients
      were instructed to (1) generate a series of 100 numbers between 1 and 9 in a
      random fashion, and (2) undertake a control serial counting task, both in
      synchrony with a 0.5 Hz pacing stimulus. Significant increases in LFP power (p <=
      0.05) across a narrow gamma frequency band (45-60 Hz) during RNG, compared to the
      control counting task, were observed. Further, the number of 'repeated pairs' (a
      decline in which reflects repetition avoidance bias in human RNG) was positively
      correlated with these gamma increases. We therefore suggest that STN gamma
      activity is relevant for controlled processing, in particular the active
      selection and repetition of the same number on successive trials. These results
      are consistent with a frequency-specific role of the STN in executive processes
      such as suppression of habitual responses and 'switching-on' of more controlled
      processing strategies.

PMID- 22960250
TI  - Non-invasive, in vivo monitoring of neuronal transport impairment in a mouse
      model of tauopathy using MEMRI.
AB  - The impairment of axonal transport by overexpression or hyperphosphorylation of
      tau is well documented for in vitro conditions; however, only a few studies on
      this phenomenon have been conducted in vivo, using invasive procedures, and with
      contradictory results. Here we used the non-invasive, Manganese-Enhanced Magnetic
      Resonance Imaging technique (MEMRI), to study for the first time a pure model of
      tauopathy, the JNPL3 transgenic mouse line, which overexpresses a mutated (P301L)
      form of the human tau protein. We show progressive impairment in neuronal
      transport as tauopathy advances. These findings are further supported by a
      significant correlation between the severity of the impairment in neuronal
      transport assessed by MEMRI, and the degree of abnormal tau assessed by
      histology. Unlike conventional techniques that focus on axonal transport
      measurement, MEMRI can provide a global analysis of neuronal transport, i.e. from
      dendrites to axons and at the macroscopic scale of fiber tracts. Neuronal
      transport impairment has been shown to be a key pathogenic process in Alzheimer's
      disease and numerous other neurodegenerative disorders. Hence, MEMRI provides a
      promising set of functional biomarkers to be used during preclinical trials to
      facilitate the selection of new drugs aimed at restoring neuronal transport in
      neurodegenerative diseases.

PMID- 22960251
TI  - Spatiotemporal characteristics and vascular sources of neural-specific and 
      nonspecific fMRI signals at submillimeter columnar resolution.
AB  - The neural specificity of hemodynamic-based functional magnetic resonance imaging
      (fMRI) signals is dependent on both the vascular regulation and the sensitivity
      of the applied fMRI technique to different types and sizes of blood vessels. In
      order to examine the specificity of MRI-detectable hemodynamic responses,
      submillimeter blood oxygenation level-dependent (BOLD) and cerebral blood volume
      (CBV) fMRI studies were performed in a well-established cat orientation column
      model at 9.4 T. Neural-nonspecific and -specific signals were separated by
      comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response
      was dominantly neural-nonspecific, mostly originating from pial and intracortical
      emerging veins, and thus was highly correlated with baseline blood volume. Uneven
      baseline CBV may displace or distort small functional domains in high-resolution
      BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal
      characteristics, a fast and early neural-nonspecific response (with 4.3-s time
      constant) and a slightly slower and delayed neural-specific response (with 9.4-s
      time constant). The nonspecific CBV signal originates from early-responding
      arteries and arterioles, while the specific CBV response, which is not correlated
      with baseline blood volume, arises from late-responding microvessels including
      small pre-capillary arterioles and capillaries. Our data indicate that although
      the neural specificity of CBV fMRI signals is dependent on stimulation duration,
      high-resolution functional maps can be obtained from steady-state CBV studies.

PMID- 22960252
TI  - Reward circuit function in high BMI individuals with compulsive overeating:
      similarities with addiction.
AB  - CONTEXT: The rising rate of overweight and obese individuals among developing
      countries despite focused efforts on prevention and treatment underscores not
      only the need to better define the physiological factors that contribute to
      weight problems, but also the need to elucidate the neurobiological mechanisms of
      the self-regulatory failure over eating that leads to weight problems. Emergent
      findings suggest an overlapping model of addiction and compulsive overeating.
      OBJECTIVE: Our goal was to examine whether neural hyper-responsivity to reward
      typically associated with substance abuse could also be seen in individuals
      exhibiting binge-eating behavior. DESIGN: Participants completed self-assessments
      of demographic information and eating behavior. Neurofunctional data were
      collected via functional MRI (fMRI) scans while participants were exposed to
      personally relevant high-calorie cues. SETTING: The participants were recruited
      from the general community. PARTICIPANTS: Twenty-six individuals with high body
      mass index (BMI)>25 and moderate binge-eating behavior as assessed by the Binge
      Eating Scale (BES) were recruited for this study. MAIN OUTCOME MEASURES: fMRI
      BOLD response during exposure to high-calorie taste cues. RESULTS: The results
      showed that exposure to high-calorie taste cues elicited fMRI BOLD response in
      the reward system of individuals with high BMI, and, more importantly, that this
      hyper-responsivity increases with greater number of binge-eating symptoms
      (cluster-corrected p<.05, z=1.9). CONCLUSIONS: These findings support an
      overlapping neural model of addiction and self-regulatory failure over eating
      that may lead to problems with weight in humans. These findings offer insight
      into the prevention and treatment of disordered eating.

PMID- 22960254
TI  - Theory of neutrinoless double-beta decay.
AB  - Neutrinoless double-beta decay, which is a very old and yet elusive process, is
      reviewed. Its observation will signal that the lepton number is not conserved and
      that the neutrinos are Majorana particles. More importantly it is our best hope
      for determining the absolute neutrino-mass scale at the level of a few tens of
      meV. To achieve the last goal certain hurdles must be overcome involving
      particle, nuclear and experimental physics. Nuclear physics is important for
      extracting useful information from the data. One must accurately evaluate the
      relevant nuclear matrix elements--a formidable task. To this end, we review the
      sophisticated nuclear structure approaches which have recently been developed,
      and which give confidence that the required nuclear matrix elements can be
      reliably calculated employing different methods: (a) the various versions of the
      quasiparticle random phase approximations, (b) the interacting boson model, (c)
      the energy density functional method and (d) the large basis interacting shell
      model. It is encouraging that, for the light neutrino-mass term at least, these
      vastly different approaches now give comparable results. From an experimental
      point of view it is challenging, since the life times are long and one has to
      fight against formidable backgrounds. One needs large isotopically enriched
      sources and detectors with high-energy resolution, low thresholds and very low
      background. If a signal is found, it will be a tremendous accomplishment. The
      real task then, of course, will be the extraction of the neutrino mass from the
      observations. This is not trivial, since current particle models predict the
      presence of many mechanisms other than the neutrino mass, which may contribute to
      or even dominate this process. In particular, we will consider the following
      processes: The neutrino induced, but neutrino-mass independent contribution.
      Heavy left and/or right-handed neutrino-mass contributions. Intermediate scalars
      (doubly charged, etc). Supersymmetric (SUSY) contributions. We will show that it
      is possible to disentangle the various mechanisms and unambiguously extract the
      important neutrino-mass scale, if all the signatures of the reaction are searched
      for in a sufficient number of nuclear isotopes.

PMID- 22960253
TI  - Development and homeostasis of the sebaceous gland.
AB  - The important role of epidermal appendages especially the sebaceous gland has
      only recently been recognized. In particular, it has been convincingly shown that
      normal development and maintenance of the sebaceous gland are required for skin
      homeostasis since atrophic sebaceous glands and disturbances in sebaceous lipid
      composition result in major defects of the physiological barrier and maintenance
      of the skin. Consequently, it is important to unravel the signaling network
      controlling proper sebaceous lineage differentiation in mammalian skin and to
      understand the underlying mechanisms leading to severe skin diseases, including
      abnormal proliferation and differentiation of the gland, defects of the lipid
      metabolism and barrier, as well as sebaceous tumor formation. Over the last
      years, results from transgenic and knock out mouse models manipulating distinct
      signaling pathways in the skin as well as the detailed analysis of human
      sebaceous gland-derived cell lines provided new insights into crucial mediators
      balancing proliferation and differentiation of the sebaceous gland. Here, we
      discuss our current knowledge of in vivo mechanisms of sebaceous gland
      development, maintenance and disorders and highlight recent contributions to the
      field of sebaceous gland biology.

PMID- 22960255
TI  - The density of tobacco retailers and its association with attitudes toward
      smoking, exposure to point-of-sale tobacco advertising, cigarette purchasing, and
      smoking among New York youth.
AB  - OBJECTIVE: Estimate the association between the density of licensed tobacco
      retailers (LTRs) and smoking-related attitudes and behaviors among middle and
      high school students in New York. METHODS: The 2000-2008 New York Youth Tobacco
      Surveys were pooled (N=70,427) and linked with county-level density of LTRs and
      retailer compliance with laws restricting youth access to cigarettes. Logistic
      regressions tested for associations with attitudes toward smoking exposure to
      point-of-sale tobacco advertising, cigarette purchasing, and smoking prevalence.
      RESULTS: LTR density is associated with self-reported exposure to point-of-sale
      advertising in New York City (NYC) among all youth (OR=1.15; 95% CI: 1.02, 1.30)
      and nonsmokers (OR=1.14; 95% CI: 1.01, 1.30); youth believing that smoking makes
      them look cool, overall (OR=1.75; 95% CI: 1.22, 2.52) and among nonsmokers
      (OR=1.68; 95% CI: 1.11, 2.55); and a counter-intuitive negative relationship with
      frequent smoking in NYC (OR=0.50; 95% CI: 0.29, 0.84). Retailer compliance was
      negatively associated with youth reporting that a retail store is their usual
      source for cigarettes (OR=0.93; 95% CI: 0.88, 0.98). CONCLUSIONS: Restricting
      tobacco licenses and enforcing youth access laws are reasonable policy approaches
      for influencing youth smoking outcomes.

PMID- 22960256
TI  - Visual experience facilitates allocentric spatial representation.
AB  - Representing the position of the objects independently from our own position is a
      fundamental cognitive ability. Here we investigated whether this ability depends
      on visual experience. Congenitally blind, late blind and blindfolded sighted
      participants haptically learnt a room-sized regularly shaped array of objects,
      and their spatial memory was tested to determine which spatial reference frame
      was used. Crucially, the use of an object-based reference frame requires
      representing the regular structure of the array. We found that blindfolded
      sighted and late blind participants, that is those with visual experience, showed
      a preferential use of the object-based or 'allocentric' reference frame. On the
      contrary, congenitally blind participants preferred a self-based, or egocentric,
      reference frame. This suggests that, due to its developmental effect on the
      multisensory brain areas involved in spatial cognition, visual experience is
      necessary to develop a preference for an object-based, allocentric reference
      frame.

PMID- 22960257
TI  - Behavioural actions of two new 1-N substituted analogues of melatonin.
AB  - Melatonin has been mainly used for alleviating some disorders related with
      insomnia and circadian rhythmicity. The use of this hormone has been limited,
      among others, due to its short half-life and instability. This study reports some
      behavioural actions of two new melatonin analogues that incorporate a phenyl or a
      benzoyl group at the nitrogen atom of the melatonin molecule. Although diazepam
      was about 10 times more potent than either of the melatonin analogues, results
      show that in general these last display better anxiolytic, anticonvulsant and
      sedative actions than the original molecule.

PMID- 22960258
TI  - Components of vestibular cortical function.
AB  - It is known that the functional response (e.g., nystagmus) to caloric vestibular
      stimulation is delayed and prolonged compared with the stimulus-response timing
      of other sensory systems. Imaging studies have used different models to predict
      cortical responses and to determine the areas of the brain that are involved.
      These studies have revealed a widespread network of vestibular brain regions.
      However, there is some disagreement regarding the brain areas involved, which may
      partly be caused by differences in the models used. This disagreement indicates
      the possible existence of multiple cortical components with different temporal
      characteristics that underlie cortical vestibular processing. However, data
      driven methods have yet to be used to analyze the underlying hemodynamic
      components during and after vestibular stimulation. We performed functional
      magnetic resonance imaging (fMRI) on 12 healthy subjects during caloric
      stimulation and analyzed these data using a model-free analysis method (ICA). We
      found seven independent stimulus-induced components that outline a robust pattern
      of cortical activation and deactivation. These independent components
      demonstrated significant differences in their time courses. No single-modeled
      response function was able to cover the entire range of these independent
      components. The response functions determined in the present study should improve
      model-based studies investigating vestibular cortical processing.

PMID- 22960259
TI  - Tip-of-the-tongue in aging: influence of vocabulary, working memory and
      processing speed.
AB  - BACKGROUND AND AIMS: It is well known that tip-of-the-tongue (ToT) states, which
      are due to failure in the phonological activation of words, especially proper
      names, are more common in older than in younger adults. Nevertheless, the
      relationship between increased numbers of ToTs and cognitive aging remains
      unclear. The aim of the present study was to clarify this relationship by
      examining ToT production and the performance of cognitive tasks such as working
      memory and processing speed tests. METHODOLOGY: In order to study the
      relationships between these constructs, the performance of 133 participants in
      different language, working memory and processing speed tasks was analysed by use
      of LISREL software. RESULTS: The best fit model included direct and indirect
      effects of age, mediated by cognitive variables, on lexical production variables.
      The model incorporated the indirect effects of age on vocabulary through working
      memory and also the indirect effect of age on ToT through processing speed.
      CONCLUSION: The results indicate negative modulation of slowed processing in the
      age-related increase of ToT and positive modulation of working memory in
      vocabulary, as well as an absence of any relation between vocabulary and ToT.
      Assuming that ToT events involve controlled processes, the relationship between
      slowed processing and ToT in aging could be interpreted as reflecting controlled
      compensatory mechanisms.

PMID- 22960260
TI  - Modulatory efficacy of rosmarinic acid on premalignant lesions and antioxidant
      status in 1,2-dimethylhydrazine induced rat colon carcinogenesis.
AB  - Colorectal cancer is one of the leading causes of cancer related deaths in
      Western countries and is becoming increasingly common in Asia. Rosmarinic acid
      (RA), one of the major components of polyphenol possesses attractive remedial
      features. The purpose of this study is to investigate the possible
      chemopreventive mechanism of action of RA against 1,2-dimethylhydrazine (DMH)
      induced rat colon carcinogenesis by evaluating the circulatory antioxidant status
      and colonic bacterial enzymes activities. Additionally, we analyzed the aberrant
      crypt foci (ACF) formation and multiplicity in the colon of experimental groups.
      Wistar male rats were divided into six groups. Group 1 was control rats, group 2
      rats received RA (10 mg/kg b.w., p.o. everyday), rats in groups 3-6 received DMH
      (20 mg/kg b.w., s.c.) for the first 4 weeks. In addition to DMH, groups 4-6
      received 2.5, 5, and 10 mg/kg b.w. RA respectively. The results revealed that
      supplementation with RA significantly reduced the formation of ACF and ACF
      multiplicity in DMH treated rats. Moreover RA supplementation prevented the
      alterations in circulatory antioxidant enzymes and colonic bacterial enzymes
      activities. Overall, our results showed that all three doses of RA inhibited
      carcinogenesis, though the effect of the intermediary dose of 5 mg/kg b.w. was
      more pronounced.

PMID- 22960261
TI  - A general P300 brain-computer interface presentation paradigm based on
      performance guided constraints.
AB  - An electroencephalographic-based brain-computer interface (BCI) can provide a non
      muscular method of communication. A general model for P300-based BCI stimulus
      presentations is introduced--the "m choose n" or C(m (number of flashes per
      sequence), n (number of flashes per item)) paradigm, which is a universal
      extension of the previously reported checkerboard paradigm (CBP). C(m,n) captures
      all possible (unconstrained) ways to flash target items, and then applies
      constraints to enhance ERP's produced by attended matrix items. We explore a
      C(36,5) instance of C(m,n) called the "five flash paradigm" (FFP) and compare its
      performance to the CBP. Eight subjects were tested in each paradigm, counter
      balanced. Twelve minutes of calibration data were used as input to a stepwise
      linear discriminant analysis to derive classification coefficients used for
      online classification. Accuracy was consistently high for FFP (88%) and CBP
      (90%); information transfer rate was significantly higher for the FFP (63 bpm)
      than the CBP (48 bpm). The C(m,n) is a novel and effective general strategy for
      organizing stimulus groups. Appropriate choices for "m," "n," and specific
      constraints can improve presentation paradigms by adjusting the parameters in a
      subject specific manner. This may be especially important for people with
      neuromuscular disabilities.

PMID- 22960262
TI  - Expression profiling of Rab GTPases reveals the involvement of Rab20 and Rab32 in
      acute brain inflammation in mice.
AB  - Rab GTPases have emerged as central regulators of vesicle trafficking and are
      essential for cytokine production during the pathogenesis of neuroinflammation.
      To characterize the roles of different Rab proteins in brain inflammation, we
      used quantitative PCR (qPCR) to examine the expression profiles of all members of
      the Rab family in an experimental model of brain inflammation in mice. We found
      that Rab20 and Rab32 were substantially up-regulated during the acute phase of
      inflammation. The increased expression of Rab20 was also confirmed by
      immunostaining of inflamed brains at different timepoints. The concomitant
      overexpression of Rabs (Rab20 and Rab32) and early response proinflammatory
      cytokines (TNF-alpha and IL-1beta) suggested that these Rabs may be important for
      subsequent inflammatory responses in brain. Furthermore, we found that the
      expression of certain Rabs was dramatically reduced in cultured primary
      microglia, which was not observed in the in vivo profiling. In N9, a microglial
      cell line, however, there was no increase in the expression of Rab20 or Rab32,
      but Rab3c was significantly overexpressed. These results collectively indicate
      that Rabs may participate in inflammatory response in microglia during brain
      inflammation. The differential regulation of individual Rabs in different
      experimental systems is a caveat for the analysis of Rab functions.

PMID- 22960263
TI  - Glycosylation of Nalpha-lauryl-O-(beta-D-xylopyranosyl)-L-serinamide as a
      saccharide primer in cells.
AB  - N(alpha)-Lauryl-O-(beta-D-xylopyranosyl)-L-serinamide (Xyl-Ser-C12) was
      synthesized as a saccharide primer to obtain oligosaccharides of
      glycosaminoglycan using the glycan biosynthetic potential of mouse osteosarcoma
      FBJ-S1 cells and Chinese hamster ovary (CHO) cells. The glycosylated products
      secreted into the culture medium were collected and analyzed by liquid
      chromatography-mass spectrometry and glycosidase digestion. The structure of the
      Xyl-Ser-C12 derivatives was investigated. Several glycosaminoglycan-type
      oligosaccharides, such as GalNAc-(GlcA-GlcNAc)(n)-GlcA-Gal-Gal-Xyl-Ser-C12, were
      detected, and identified as intermediates of the biosynthesis of heparan sulfate
      glycosaminoglycans. Xyl-Ser-C12 exhibited greater acceptor activity for the
      glycosylation of glycosaminoglycan-type oligosaccharides than p-nitrophenyl-beta
      D-xylopyranoside.

PMID- 22960264
TI  - Critical role of Th17 cells in development of autoimmune hemolytic anemia.
AB  - Autoimmune hemolytic anemia (AIHA) is defined as the increased destruction of red
      blood cells (RBCs) in the presence of anti-RBC autoantibodies with or without
      complement activation. However, the underlying mechanism for the development of
      AIHA remains largely unclear. In this study, we carefully evaluated the potential
      role of Th17 cells in the development of AIHA. We found an elevated frequency of
      Th17 cells in patients with AIHA, which were closely correlated with their
      disease activity, including the level of anti-RBC IgG antibodies, hemoglobin,
      serum C3, and lactate dehydrogenase activity. Furthermore, we observed that
      interleukin (IL)-17 was also closely correlated with the disease activity in AIHA
      patients. To further elucidate the potential role of Th17 cells in induction of
      AIHA, we used the Marshall-Clarke and Playfair model of murine AIHA. Notably, we
      found that Th17 cells affected development of AIHA by enhancing the adaptive
      humoral responses. Specifically, we found that adoptive transfer of Th17 cells
      heightened the initial anti-rat RBC antibody responses and concomitantly
      increased the onset of AIHA. In addition, in vivo neutralization of IL-17
      abrogated the development of AIHA, while initiation of anti-rat RBC IgG responses
      and induction of AIHA in IL-17(-/-) mice were impaired. Our findings suggest that
      Th17 cells contribute to the development of AIHA, which could facilitate our
      better understanding of AIHA pathogenesis and provide clues to developing novel
      forms of immunotherapy against AIHA.

PMID- 22960265
TI  - SHP-1 protein tyrosine phosphatase associates with the adaptor protein CrkL.
AB  - SHP-1, encoded by the PTPN6 gene, is a protein tyrosine phosphatase with two src
      homology-2 (SH2) domains that is implicated as providing suppression of
      hematopoietic malignancies. A number of reports have shown protein-protein
      interactions between SHP-1 SH2 domains and tyrosine-phosphorylated proteins.
      However, despite its having three proline-rich, potential SH3-binding motifs, no
      reports of protein-protein interactions through src-homology-3 (SH3)-binding
      domains with SHP-1 have been described. Herein we show that the SH3 domain
      containing CT10 regulator of kinase-like (CrkL) adaptor protein associates with
      SHP-1. We also provide results that suggest this association is due to CrkL
      binding to PxxP domains located at amino acid residues 158-161 within the SHP-1 C
      terminal SH2 domain, and amino acid residues 363-366 within its phosphatase
      domain. This study is the first to identify and define an interaction between SHP
      1 and an SH3 domain-containing protein. Our findings provide an alternative way
      that SHP-1 can be linked to potential substrates.

PMID- 22960266
TI  - Percutaneous ultrasonography and computed tomography guided pancreatic
      cryoablation: feasibility and safety assessment.
AB  - OBJECTIVE: To assess the safety and feasibility of percutaneous cryoablation on
      pancreatic cancer via ultrasonography (US) and computed tomography (CT) guidance.
      MATERIALS AND METHODS: This retrospective review was approved by the
      institutional review board and of informed consent. Thirty-two patients (18 men
      and 14 women; median age 62; age range, 30-77 years) with pancreatic cancer
      (stage II/III/IV, 3/11/18) treated with percutaneous US and CT guided
      cryoablations between February 2009 and February 2010 were eligible for this
      review. Thirteen tumors in pancreatic head and 19 in pancreatic body and/or tail
      measuring 2-11 cm (mean, 5.2 cm+/-8 [standard deviation]) were ablated with 49
      procedures in total. Feasibility was analyzed by enhanced CT 1-3 months post
      procedure and safety was assessed by clinical signs, symptoms and laboratory
      results. RESULTS: Neither procedural death nor serious complications occurred.
      Fifteen tumors (46.9%) smaller than 5 cm were successfully ablated by one session
      of cryoablation. Twenty-seven patients experienced a >=50% reduction in pain
      score, 22 experienced a 50% decrease in analgesic consumption and 16 experienced
      a >=20 increase in Karnofsky Performance Status (KPS) Score. Partial response
      (PR) and stable disease (SD) turned up in 9 and 21 patients, respectively,
      lesions in whom were identified controlled by none enhancement on enhanced CT.
      Mean and median survival was 15.9 and 12.6 months, respectively. The 6-, 12- and
      24-month survival rates were 82.8%, 54.7% and 27.3%, respectively. CONCLUSION: US
      and CT guided percutaneous cryoablation is a safe and promising local treatment
      for pancreatic cancer.

PMID- 22960267
TI  - Exploration of deleterious single nucleotide polymorphisms in late-onset
      Alzheimer disease susceptibility genes.
AB  - Non-synonymous single nucleotide polymorphisms (nsSNPs) are considered as
      biomarkers to disease susceptibility. In the present study, nsSNPs in CLU, PICALM
      and BIN1 genes were screened for their functional impact on concerned proteins
      and their plausible role in Alzheimer disease (AD) susceptibility. Initially,
      SNPs were retrieved from dbSNP database, followed by identification of
      potentially deleterious nsSNPs and prediction of their effect on proteins by
      PolyPhen and SIFT. Protein stability and the probability of mutation occurrence
      were predicted using I-Mutant and PANTHER respectively. SNPs3D and FASTSNP were
      used for the functional analysis of nsSNPs. The functional impact on the 3D
      structure of proteins was evaluated by SWISSPDB viewer and NOMAD-Ref server. On
      analysis, 3 nsSNPs with IDs rs12800974 (T158P) of PICALM and rs11554585 (R397C)
      and rs11554585 (N106D) of BIN1 were predicted to be functionally significant with
      higher scores of I-Mutant, SIFT, PolyPhen, PANTHER, FASTSNP and SNPs3D. The
      mutant models of these nsSNPs also showed very high energies and RMSD values
      compared to their native structures. Current study proposes that the three nsSNPs
      identified in this study constitute a unique resource of potential genetic
      factors for AD susceptibility.

PMID- 22960268
TI  - Identification of a new clock-related element EL-box involved in circadian
      regulation by BMAL1/CLOCK and HES1.
AB  - Several cis-acting elements play critical roles in maintaining circadian
      expression of clock and clock-controlled genes. Using in silico analysis, we
      identified 10 sequence motifs that are correlated with the circadian phases of
      gene expression in the cartilage. One of these motifs, an E-box-like clock
      related element (EL-box; GGCACGAGGC), can mediate BMAL1/CLOCK-induced
      transcription, which is typically regulated through an E-box or E'-box.
      Expression of EL-box-containing genes, including Ank, Dbp, and Nr1d1 (Rev
      erbalpha), was induced by BMAL1/CLOCK or BMAL1/NPAS2. Compared with the E-box,
      the EL-box elements had distinct responsiveness to DEC1, DEC2, and HES1:
      suppressive actions of DEC1 and DEC2 on the EL-box were less potent than those on
      the E-box. HES1, which is known to bind to the N-box (CACNAG), suppressed
      enhancer activity of the EL-box, but not the E-box. In the Dbp promoter, an EL
      box worked cooperatively with a noncanonical (NC) E-box to mediate BMAL1/CLOCK
      actions. These findings suggest that in addition to known clock elements, the EL
      box element may contribute to circadian regulation of clock and clock-controlled
      genes.

PMID- 22960269
TI  - Increased EEG sigma and beta power during NREM sleep in primary insomnia.
AB  - The hyperarousal model of primary insomnia suggests that a deficit of attenuating
      arousal during sleep might cause the experience of non-restorative sleep. In the
      current study, we examined EEG spectral power values for standard frequency bands
      as indices of cortical arousal and sleep protecting mechanisms during sleep in 25
      patients with primary insomnia and 29 good sleeper controls. Patients with
      primary insomnia demonstrated significantly elevated spectral power values in the
      EEG beta and sigma frequency band during NREM stage 2 sleep. No differences were
      observed in other frequency bands or during REM sleep. Based on prior studies
      suggesting that EEG beta activity represents a marker of cortical arousal and EEG
      sleep spindle (sigma) activity is an index of sleep protective mechanisms, our
      findings may provide further evidence for the concept that a simultaneous
      activation of wake-promoting and sleep-protecting neural activity patterns
      contributes to the experience of non-restorative sleep in primary insomnia.

PMID- 22960270
TI  - Weekend-weekday advances in sleep timing are associated with altered reward
      related brain function in healthy adolescents.
AB  - Sleep timing shifts later during adolescence, thus conflicting with early school
      start times. This can lead to irregular weekday-weekend schedules and circadian
      misalignment, which have been linked to depression and substance abuse,
      consistent with disruptions in the processing of rewards. We tested associations
      between weekend-weekday shifts in sleep timing and the neural response to
      monetary reward in healthy adolescents, using actigraphy and a functional
      magnetic resonance imaging paradigm. Region-of-interest analyses focused on the
      medial prefrontal cortex (mPFC) and striatum, both of which are implicated in
      reward function. Analyses adjusted for pubertal stage, sex, and total sleep time.
      Greater weekend-weekday advances in midsleep were associated with decreased mPFC
      and striatal reactivity to reward, which could reflect reduced regulatory
      response and reward sensitivity. We speculate that circadian misalignment
      associated with weekend shifts in sleep timing may contribute to reward-related
      problems such as depression and substance abuse.

PMID- 22960272
TI  - Dissociation between memory reactivation and its behavioral expression:
      scopolamine interferes with memory expression without disrupting long-term
      storage.
AB  - The reconsolidation hypothesis has challenged the traditional view of fixed
      memories after consolidation. Reconsolidation studies have disclosed that the
      mechanisms mediating memory retrieval and the mechanisms that underlie the
      behavioral expression of memory can be dissociated, offering a new prospect for
      understanding the nature of experimental amnesia. The muscarinic antagonist
      scopolamine has been used for decades to induce experimental amnesias The goal of
      the present study is to determine whether the amnesic effects of scopolamine are
      due to storage (or retrieval) deficits or, alternatively, to a decrease in the
      long-term memory expression of a consolidated long-term memory. In the crab
      Chasmagnathus memory model, we found that scopolamine-induced amnesia can be
      reverted by facilitation after reminder presentation. This recovery of memory
      expression was reconsolidation specific since a reminder that does not triggers
      reconsolidation process did not allow the recovery. A higher dose (5 MUg/g) of
      scopolamine induced an amnesic effect that could not be reverted through
      reconsolidation, and thus it can be explained as an interference with memory
      storage and/or retrieval mechanisms. These results, showing that an effective
      amnesic dose of scopolamine (100 ng/g) negatively modulates long-term memory
      expression but not memory storage in the crab Chasmagnathus, are consistent with
      the concept that dissociable processes underlie the mechanisms mediating memory
      reactivation and the behavioral expression of memory.

PMID- 22960271
TI  - Protease-activated receptor 2 signaling upregulates angiogenic growth factors in
      renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a highly vascular tumor associated with expression
      of various angiogenic growth factors. The precise process of how these growth
      factors are regulated in RCC is not fully understood. Recent evidence suggests
      that protease activated receptors (PARs), a new family of G-protein coupled
      receptors, play a crucial role in vascular development and tumor progression
      through a variety of mechanisms. However, the nature of PAR expression in human
      RCC tissues and its function in regulating angiogenesis in RCC are largely
      unknown. In this study, we investigated the expression and function of PAR-2 in
      RCC. RT-PCR and immunohistochemistry assays show that PAR-2 expression is
      significantly increased in human RCC tissue compared with the adjacent non
      neoplastic kidney tissue. In RCC derived cells, PAR-2 is functional as evidenced
      by robust signaling through MAP kinases including ERK1/2 and JNK. Furthermore,
      activation of PAR-2 significantly upregulates several angiogenic cytokines,
      including interleukin-6 (IL-6), IL-8, monocytes chemotactic protein-1 (MCP-1) and
      growth-related oncogene (GRO). To our knowledge, this is the first report that
      characterized PAR-2 expression in RCC tissue and further demonstrated that PAR-2
      has a critical role in regulating angiogenesis in RCC.

PMID- 22960273
TI  - Genome-wide DNA methylation profiling identifies ALDH1A3 promoter methylation as
      a prognostic predictor in G-CIMP- primary glioblastoma.
AB  - To date, the aberrations in the DNA methylation patterns that are associated with
      different prognoses of G-CIMP- primary GBMs remain to be elucidated. Here, DNA
      methylation profiling of primary GBM tissues from 13 long-term survivors (LTS;
      overall survival ?18months) and 20 short-term survivors (STS; overall survival
      ?9months) was performed. Then G-CIMP+ samples were excluded. The differentially
      expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP-
      samples. Methylation levels of 11 CpG loci (10genes) were statistically
      significantly lower, and 43 CpG loci (40genes) were statistically significantly
      higher in the tumor tissues of LTS than those of STS G-CIMP- samples (P<0.01). Of
      the 43 CpG loci that were hypermethylated in LTS G-CIMP- samples, 3 CpG loci
      localized in the promoter of ALDH1A3. Furthermore, using an independent
      validation cohort containing 37 primary GBM samples without IDH1 mutation and
      MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter
      predicted a better prognosis with an accompanied low expression of ALDH1A3
      protein. Taken together, our results defined prognosis-related methylation
      signatures systematically for the first time in G-CIMP- primary GBMs. ALDH1A3
      promoter methylation conferred a favorable prognosis in G-CIMP- primary GBMs.

PMID- 22960276
TI  - Does exercise reduce pain and improve physical function before hip or knee
      replacement surgery? A systematic review and meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: To investigate the preoperative effects of exercise-based
      interventions on pain and physical function for people awaiting joint replacement
      surgery of the hip or knee. DATA SOURCES: Four computer databases (CINAHL,
      MEDLINE, Embase, and Cochrane Library) were searched until July 4, 2012. Search
      terms included knee, hip, joint replacement, arthroplasty, physiotherapy,
      physical therapy, exercise, hydrotherapy, rehabilitation, and preoperative.
      Reference lists of retrieved articles were also screened. STUDY SELECTION:
      Randomized or quasi-randomized studies comparing an exercise-based intervention
      with a no-intervention group for people awaiting hip or knee joint replacement
      surgery were included. Outcomes were pain and physical function including self
      reported function, walking speed, and muscle strength. One of 2 reviewers
      determined that 18 studies met the inclusion criteria. DATA EXTRACTION: The
      methodologic quality of each study was independently assessed by 2 reviewers
      using the PEDro scale, and a final PEDro score was determined by discussion and
      consensus between the reviewers. Participants' characteristics, content and
      design of the interventions, and data for quantitative synthesis were extracted
      by 1 reviewer. DATA SYNTHESIS: For participants awaiting knee replacement
      surgery, quantitative data synthesis found no significant differences between the
      exercise and no-intervention groups for pain, self-reported function, walking
      speed, or muscle strength. For participants awaiting hip replacement surgery,
      quantitative data synthesis found a significant difference between the groups,
      with standardized mean differences (SMDs) indicating a medium-sized effect in
      favor of intervention for both pain (SMD=.45; 95% confidence interval .15-.75)
      and self-reported function (SMD=.46; 95% confidence interval .20-.72).
      CONCLUSIONS: Exercise-based interventions can reduce pain and improve physical
      function for people awaiting hip replacement surgery but not knee replacement
      surgery.

PMID- 22960275
TI  - Effect of a safe patient handling program on rehabilitation outcomes.
AB  - OBJECTIVE: To evaluate the effect of a safe patient handling (SPH) program on
      rehabilitation mobility outcomes. DESIGN: Retrospective cohort study. SETTING: A
      rehabilitation unit in a hospital system. PARTICIPANTS: Consecutive patients
      (N=1291) over a 1-year period without an SPH program in place (n=507) and
      consecutive patients over a 1-year period with an SPH program in place (n=784).
      INTERVENTIONS: The SPH program consisted of administrative policies and patient
      handling technologies. The policies limited manual patient handling. Equipment
      included ceiling- and floor-based dependent lifts, sit-to-stand assists,
      ambulation aides, friction-reducing devices, motorized hospital beds and shower
      chairs, and multihandled gait belts. MAIN OUTCOME MEASURES: The mobility subscale
      of the FIM. RESULTS: Patients rehabilitated in the group with SPH achieved
      similar outcomes to patients rehabilitated in the group without SPH. A
      significant difference between groups was noted for patients with initial
      mobility FIM scores of 15.1 and higher after controlling for initial mobility FIM
      score, age, length of stay, and diagnosis. Those patients performed better with
      SPH. CONCLUSIONS: SPH programs do not appear to inhibit recovery. Fears among
      therapists that the use of equipment may lead to dependence may be unfounded.

PMID- 22960274
TI  - ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide
      induced apoptosis.
AB  - The present study aims to determine the effect of AMPK on etoposide-induced
      apoptosis of cancer cells. Our results revealed that etoposide induced AMPK
      activation in prostate C4-2 cancer cells, an event that was attenuated by ATM
      siRNA. In A549 cells that lack LKB1, AMPK was unable to be activated by
      etoposide, which was restored by introduction of LKB1. Likewise, silencing LKB1
      in C4-2 cells impaired AMPK activation. Finally, etoposide displayed a potent pro
      apoptotic effect in cancer cells with functional LKB1 and AMPK. Thus, our results
      establish a linear relationship of ATM, LKB1 and AMPK in response to the DNA
      damage drug.

PMID- 22960277
TI  - Relative and absolute reliabilities of the myotonometric measurements of
      hemiparetic arms in patients with stroke.
AB  - OBJECTIVE: To investigate the relative and absolute reliabilities of the
      myotonometer. DESIGN: Psychometric study. SETTING: Three medical centers.
      PARTICIPANTS: Patients with stroke (N=61). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Muscle tone, elasticity, and stiffness of relaxed affected
      deltoid, triceps brachii, biceps brachii, extensor digitorum, flexor carpi
      radialis, and flexor carpi ulnaris were measured twice, 30 minutes apart, using
      the myotonometer. Intraclass correlation coefficient, a relative reliability
      index, was calculated for 3 muscular properties and for each muscle to examine
      the degree of consistency and agreement between the 2 test sessions. Absolute
      reliability indices, including the SEM, smallest real difference, and Bland
      Altman limits of agreement, were used to quantify measurement errors and check
      systematic biases of the 2 test sessions. RESULTS: The intraclass correlation
      coefficients were .83 to .95 for muscle tone, elasticity, and stiffness of all
      muscle groups. The SEM and the smallest real difference of muscle tone,
      elasticity, and stiffness of the biceps were the smallest among the 6 muscles
      tested. The Bland-Altman analyses showed no systematic bias between most of the
      repeated measurements. Compared with other muscles, biceps had narrower limits-of
      agreement ranges, indicating that the myotonometric measurements of the biceps
      had higher stability and less variation over time. CONCLUSIONS: The myotonometer
      reliably measures muscular properties, with good relative and absolute
      reliabilities. These findings are useful for clinicians and researchers to assess
      muscle properties reliably and determine whether a real change has occurred in
      groups and on individual levels of patients with stroke.

PMID- 22960278
TI  - The attenuation of cockroach allergy by DNA vaccine encoding cockroach allergen
      Bla g 2.
AB  - Bla g 2 is one of the most potent cockroach allergens. No effective treatment or
      vaccination strategies are yet available. We evaluated the prophylactic efficacy
      of Bla g 2 DNA vaccination in a mouse model of allergic airway inflammation.
      C57/BL6 mice were given Bla g 2 DNA vaccine prior to sensitization with
      recombinant Bla g 2 (rBla g 2) antigens, followed by nebulized rBla g 2
      challenge. Bla g 2 vaccine could express at both transcriptional and
      translational levels in mammalian cells. Moreover, Bla g 2 vaccine significantly
      reduced the total inflammatory cell infiltrate and eosinophilia in
      bronchoalveolar lavage fluid, and markedly decreased allergen-induced
      inflammatory infiltrates in the lungs and Bla g 2-specific IgE in serum upon
      challenge with rBla g 2. Importantly, Bla g 2 vaccine could induce the production
      of antigen-specific IFN-gamma and downregulated Th2 pro-inflammatory cytokines IL
      4, IL-5, and IL-13. Thus, DNA vaccination showed protective efficacy against a
      clinically relevant allergen, Bla g 2.

PMID- 22960279
TI  - 17beta-Estradiol enhances response of mice spleen B cells elicited by TLR9
      agonist.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      production of autoantibodies against nucleic acid-associated antigens. B cells
      play cardinal roles in SLE. Many evidences have proved estrogen contribute to the
      gender bias in SLE and 17beta-estradiol (E2) could accelerate the disease by
      regulating B cells. On the other hand, B cells express TLR9 which recognized
      dsDNA and played a critical role in SLE. However, the crosstalk between estrogen
      and TLR9 in B cells remains unknown. So we investigated the E2 effect in the
      presence of the TLR9 ligand CpG on mice spleen B cells. We found that the up
      regulation of cell viability, life-span, co-stimulation molecules (CD40, CD86)
      expression, IgM secretion, TLR9 and MCM6 expression were more significant than
      CpG ODN or E2 stimulated alone. It may provide a new way to investigate the
      mechanism of how E2 modulate the B cells function in lupus.

PMID- 22960280
TI  - VSTM1-v2, a novel soluble glycoprotein, promotes the differentiation and
      activation of Th17 cells.
AB  - Cytokines are soluble proteins that mediate immune reactions and are responsible
      for communication among immune cells. CD4(+) T cells are the principle sources of
      cytokines of adaptive immunity. Cytokines play critical roles in the
      differentiation and effector function of CD4(+) T cells. They also play key roles
      in diseases, and some of them have been developed into drugs in the forms of
      recombinant cytokines, soluble receptors and neutralizing antibodies. Therefore,
      identifying novel potential cytokines is necessary and beneficial for better
      understanding immunology and enhancing human health. To find novel potential
      cytokines, we carried out an integrated bioinformatics analysis on the whole
      human genome. Cytokine candidates were selected for cDNA cloning, sub-cloning,
      secretion verification, expression profile analysis and functional study. Here,
      we report a novel soluble protein, VSTM1-v2, which is a classical secretory
      glycoprotein mainly expressed in immune tissues, and can promote the
      differentiation and activation of Th17 cells.

PMID- 22960281
TI  - The regulatory factor PcRFX1 controls the expression of the three genes of beta
      lactam biosynthesis in Penicillium chrysogenum.
AB  - Penicillin biosynthesis is subjected to a complex regulatory network of
      signalling molecules that may serve as model for other secondary metabolites. The
      information provided by the new "omics" era about Penicillium chrysogenum and the
      advances in the knowledge of molecular mechanisms responsible for improved
      productivity, make this fungus an excellent model to decipher the mechanisms
      controlling the penicillin biosynthetic pathway. In this work, we have
      characterized a novel transcription factor PcRFX1, which is an ortholog of the
      Acremonium chrysogenum CPCR1 and Penicillium marneffei RfxA regulatory proteins.
      PcRFX1 DNA binding sequences were found in the promoter region of the pcbAB, pcbC
      and penDE genes. We show in this article that these motifs control the expression
      of the beta-galactosidase lacZ reporter gene, indicating that they may direct the
      PcRFX1-mediated regulation of the penicillin biosynthetic genes. By means of
      Pcrfx1 gene knock-down and overexpression techniques we confirmed that PcRFX1
      controls penicillin biosynthesis through the regulation of the pcbAB, pcbC and
      penDE transcription. Morphology and development seemed not to be controlled by
      this transcription factor under the conditions studied and only sporulation was
      slightly reduced after the silencing of the Pcrfx1 gene. A genome-wide analysis
      of processes putatively regulated by this transcription factor was carried out in
      P. chrysogenum. Results suggested that PcRFX1, in addition to regulate penicillin
      biosynthesis, is also involved in the control of several pathways of primary
      metabolism.

PMID- 22960282
TI  - Cross species analysis of Prominin reveals a conserved cellular role in
      invertebrate and vertebrate photoreceptor cells.
AB  - The two fundamental types of photoreceptor cells have evolved unique structures
      to expand the apical membrane to accommodate the phototransduction machinery,
      exemplified by the cilia-based outer segment of the vertebrate photoreceptor cell
      and the microvilli-based rhabdomere of the invertebrate photoreceptor. The
      morphogenesis of these compartments is integral for photoreceptor cell integrity
      and function. However, little is known about the elementary cellular and
      molecular mechanisms required to generate these compartments. Here we investigate
      whether a conserved cellular mechanism exists to create the phototransduction
      compartments by examining the functional role of a photoreceptor protein common
      to both rhabdomeric and ciliated photoreceptor cells, Prominin. First and
      foremost we demonstrate that the physiological role of Prominin is conserved
      between rhabdomeric and ciliated photoreceptor cells. Human Prominin1 is not only
      capable of rescuing the corresponding rhabdomeric Drosophila prominin mutation
      but also demonstrates a conserved genetic interaction with a second photoreceptor
      protein Eyes Shut. Furthermore, we demonstrate the Prominin homologs in
      vertebrate and invertebrate photoreceptors require the same structural features
      and post-translational modifications for function. Moreover, expression of mutant
      human Prominin1, associated with autosomal dominant retinal degeneration, in
      rhabdomeric photoreceptor cells disrupts morphogenesis in ways paralleling
      retinal degeneration seen in ciliated photoreceptors. Taken together, our results
      suggest the existence of an ancestral Prominin-directed cellular mechanism to
      create and model the apical membranes of the two fundamental types of
      photoreceptor cells into their respective phototransduction compartments.

PMID- 22960283
TI  - Wnt signaling though beta-catenin is required for prostate lineage specification.
AB  - Androgens initiate a complex network of signals within the UGS that trigger
      prostate lineage commitment and bud formation. Given its contributions to
      organogenesis in other systems, we investigated a role for canonical Wnt
      signaling in prostate development. We developed a new method to achieve complete
      deletion of beta-catenin, the transcriptional coactivator required for canonical
      Wnt signaling, in early prostate development. Beta-catenin deletion abrogated
      canonical Wnt signaling and yielded prostate rudiments that exhibited
      dramatically decreased budding and failed to adopt prostatic identity. This
      requirement for canonical Wnt signaling was limited to a brief critical period
      during the initial molecular phase of prostate identity specification. Deletion
      of beta-catenin in the adult prostate did not significantly affect organ
      homeostasis. Collectively, these data establish that beta-catenin and Wnt
      signaling play key roles in prostate lineage specification and bud outgrowth.

PMID- 22960285
TI  - Structure analysis of the membrane-bound PhoD signal peptide of the Tat
      translocase shows an N-terminal amphiphilic helix.
AB  - Tat signal peptides provide the key signature for proteins that get exported by
      the bacterial twin arginine translocase. We have characterized the structure of
      the PhoD signal peptide from Bacillus subtilis in suitable membrane-mimicking
      environments. High-resolution 13C/15N NMR analysis in detergent micelles revealed
      a helical stretch in the signal peptide between positions 5 and 15, in good
      agreement with secondary structure prediction and circular dichroism results.
      This helix was found to be aligned parallel to the membrane surface according to
      oriented circular dichroism experiments carried out with planar lipid bilayers.
      The N-terminal alpha-helix exhibits a pronounced amphiphilic character, in
      contrast to the general view in the literature. So far, signal sequences had been
      supposed to consist of a positively charged N-terminal domain, followed by an
      alpha-helical hydrophobic segment, plus a C-terminal domain carrying the
      peptidase cleavage site. Based on our new structural insights, we propose a model
      for the folding and membrane interactions of the Tat signal sequence from PhoD.

PMID- 22960286
TI  - Interaction of gramicidin with DPPC/DODAB bilayer fragments.
AB  - The interaction between the antimicrobial peptide gramicidin (Gr) and
      dipalmitoylphosphatidylcholine (DPPC)/dioctadecyldimethylammonium bromide (DODAB)
      1:1 large unilamellar vesicles (LVs) or bilayer fragments (BFs) was evaluated by
      means of several techniques. The major methods were: 1) Gr intrinsic fluorescence
      and circular dichroism (CD) spectroscopy; 2) dynamic light scattering for sizing
      and zeta-potential analysis; 3) determination of the bilayer phase transition
      from extrinsic fluorescence of bilayer probes; 4) pictures of the dispersions for
      evaluation of coloidal stability over a range of time and NaCl concentration. For
      Gr in LVs, the Gr dimeric channel conformation is suggested from: 1) CD and
      intrinsic fluorescence spectra similar to those in trifluoroethanol (TFE); 2) KCl
      or glucose permeation through the LVs/Gr bilayer. For Gr in BFs, the intertwined
      dimeric, non-channel Gr conformation is evidenced by CD and intrinsic
      fluorescence spectra similar to those in ethanol. Both LVs and BFs shield Gr
      tryptophans against quenching by acrylamide but the Stern-Volmer quenching
      constant was slightly higher for Gr in BFs confirming that the peptide is more
      exposed to the water phase in BFs than in LVs. The DPPC/DODAB/Gr supramolecular
      assemblies may predict the behavior of other antimicrobial peptides in assemblies
      with lipids.

PMID- 22960284
TI  - New perspectives on pharyngeal dorsoventral patterning in development and
      evolution of the vertebrate jaw.
AB  - Patterning of the vertebrate facial skeleton involves the progressive
      partitioning of neural-crest-derived skeletal precursors into distinct
      subpopulations along the anteroposterior (AP) and dorsoventral (DV) axes. Recent
      evidence suggests that complex interactions between multiple signaling pathways,
      in particular Endothelin-1 (Edn1), Bone Morphogenetic Protein (BMP), and Jagged
      Notch, are needed to pattern skeletal precursors along the DV axis. Rather than
      directly determining the morphology of individual skeletal elements, these
      signals appear to act through several families of transcription factors,
      including Dlx, Msx, and Hand, to establish dynamic zones of skeletal
      differentiation. Provocatively, this patterning mechanism is largely conserved
      from mouse and zebrafish to the jawless vertebrate, lamprey. This implies that
      the diversification of the vertebrate facial skeleton, including the evolution of
      the jaw, was driven largely by modifications downstream of a conversed pharyngeal
      DV patterning program.

PMID- 22960287
TI  - Characterization of co-translationally formed nanodisc complexes with small
      multidrug transporters, proteorhodopsin and with the E. coli MraY translocase.
AB  - Nanodiscs (NDs) enable the analysis of membrane proteins (MP) in natural lipid
      bilayer environments. In combination with cell-free (CF) expression, they could
      be used for the co-translational insertion of MPs into defined membranes. This
      new approach allows the characterization of MPs without detergent contact and it
      could help to identify effects of particular lipids on catalytic activities.
      Association of MPs with different ND types, quality of the resulting MP/ND
      complexes as well as optimization parameters are still poorly analyzed. This
      study describes procedures to systematically improve CF expression protocols for
      the production of high quality MP/ND complexes. In order to reveal target
      dependent variations, the co-translational ND complex formation with the
      bacterial proton pump proteorhodopsin (PR), with the small multidrug resistance
      transporters SugE and EmrE, as well as with the Escherichia coli MraY translocase
      was studied. Parameters which modulate the efficiency of MP/ND complex formation
      have been identified and in particular effects of different lipid compositions of
      the ND membranes have been analyzed. Recorded force distance pattern as well as
      characteristic photocycle dynamics indicated the integration of functionally
      folded PR into NDs. Efficient complex formation of the E. coli MraY translocase
      was dependent on the ND size and on the lipid composition of the ND membranes.
      Active MraY protein could only be obtained with ND containing anionic lipids,
      thus providing new details for the in vitro analysis of this pharmaceutically
      important protein.

PMID- 22960288
TI  - Effect of exenatide on cholecystokinin-induced gallbladder emptying in fasting
      healthy subjects.
AB  - Exenatide is a glucagon-like peptide-1 receptor agonist for the treatment of type
      2 diabetes and has been shown to lower blood glucose through multiple mechanisms,
      including glucose-dependent insulin secretion, suppression of postprandial
      glucagon release and slowing of gastric emptying. The effects of exenatide on
      biliary motility are unknown. This study evaluated the effect of a single dose of
      exenatide on cholecystokinin (CCK)-induced gallbladder emptying. Healthy subjects
      participated in this randomized, 2-period, double-blind crossover study. Fasting
      subjects received a single subcutaneous injection of exenatide (10 MUg) or
      placebo 60 min before CCK infusion. Gallbladder volume and ejection fraction (EF)
      were assessed by ultrasonography before, during, and after CCK infusion (0.003
      MUg/kg infused over 50 min at 2 mL/min). The diameters of the main pancreatic
      duct and common bile duct were measured sonographically at the same time points
      before, during, and following CCK infusion. Administration of exenatide did not
      affect pre-CCK infusion gallbladder volume or EF compared to placebo. During the
      CCK-infusion, the mean minimum gallbladder volume was similar for exenatide
      (13.68 mL) and placebo (11.05 mL) (least squares mean [LSM] difference of 2.62
      mL; 95% confidence interval [CI], -0.53, 5.78), but the mean maximum EF was lower
      for exenatide (28.79%) versus placebo (46.13%) (LSM difference of -17.34%; 95%
      CI, -30.54, -4.13). Exenatide had no clinically significant effects on pancreatic
      or bile duct diameters. In conclusion, exenatide reduced CCK-induced gallbladder
      emptying compared with placebo in fasting healthy subjects.

PMID- 22960289
TI  - Myocardial angiogenesis after chronic ghrelin treatment in a rat myocardial
      infarction model.
AB  - Ghrelin has a protective role in a rat model of myocardial infarction (MI), but
      the underlying mechanism is not clear. Here, we investigated the effects of
      ghrelin treatment on angiogenesis in an experimental rat MI model. Adult male
      Sprague-Dawley rats were subjected to MI by ligating the anterior descending
      coronary artery. The rats were then treated with a subcutaneous injection of
      ghrelin (100 MUg/kg) or saline (control group) for 4 weeks. Sham animals
      underwent thoracotomy and pericardiotomy, but not LAD ligation. At 28 days after
      ligation, the ghrelin treatment group showed a higher density of alpha-SMA
      positive vessels than the saline treatment MI group in myocardial infarct (6+/
      2.1/mm(2) vs 4+/-1.8/mm(2), P<0.05) and peri-infarct zones (25+/-9.5/mm(2) vs
      15+/-5.7/mm(2), P<0.05). RT-PCR and western-blot analyses showed that ghrelin
      significantly increased vascular endothelial growth factor (VEGF) expression in
      the peri-infarct zone compared with the control group. Moreover, there was a two
      fold increase of Bcl-2 and a 3.5-fold reduction of the Bax protein in the ghrelin
      treated MI group compared to the saline treatment MI group. Taken together,
      ghrelin could induce angiogenesis in rats after MI, the process that may be
      associated with the enhancement of VEGF and an anti-apoptosis effect.

PMID- 22960290
TI  - The influence of age and gender on antioxidant enzyme activities in humans and
      laboratory animals.
AB  - Antioxidative/oxidative balance is one of the important factors for homeostasis.
      Antioxidative systems which protect from peroxidative damage are supposed to be
      under the influence of steroid hormones. The implications of this influence are
      age and gender as well as tissue dependent alterations in antioxidative enzyme
      activities. Apart from hormonal influence, antioxidative enzymes require the
      presence of microelements in their active centers as well as concerted action of
      non enzymatic antioxidants which support enzymes in their scavenging action. The
      aim of this review is to analyze and compare existing knowledge about the changes
      in activity of antioxidant enzymes in human and animal females and males of
      different age. Evidence as regards participation of oxidative stress in
      senescence are specific diseases which, to some extent, are gender dependent and
      appear more frequently in males or females. Several experiments in laboratory
      animals revealed that changes in enzyme activities are reflected in
      histopathological pictures of cells. The alterations observed during
      perimenopausal period provide with additional evidence of the participation of
      steroid hormones in the regulation of antioxidative system activity. Moreover,
      estrogens themselves exhibit antioxidative activity which is receptor
      independent. In conclusion, apart from genetic-related influences, also diet and
      style of life may have an impact on the antioxidative system which requires
      appropriate supplementation in microelements and vitamins for its effective
      function of scavenging excess of free radicals.

PMID- 22960291
TI  - Child abuse physicians: coping with challenges.
AB  - This article explores how child abuse physicians (CAPs) experience the unique
      challenges of the emerging field of child abuse pediatrics. Practicing CAPs
      completed a written survey about known challenges in their field. Fifty-six CAPs
      completed the written survey and reported experiencing many negative consequences
      including: threats to their personal safety (52%), formal complaints to
      supervisors (50%) and licensing bodies (13%), negative stories in the media
      (23%), and malpractice suits (16%). A purposeful sample of CAPs participated in
      telephone interviews about these challenges. The 19 physicians who were
      interviewed described the challenges, while they spontaneously expressed
      satisfaction with their career and described some strategies for coping with the
      stresses of child abuse pediatrics. The findings highlight the stressors and
      challenges that may affect the ability to maintain an adequate CAP workforce.
      Better understanding of the challenges should help prepare physicians to practice
      this subspecialty.

PMID- 22960292
TI  - Positive feedback and temperature mediated molecular switch controls differential
      gene regulation in Bordetella pertussis.
AB  - Based on the phosphorelay kinetics operative within BvgAS two component system we
      propose a mathematical framework for signal transduction and gene regulation of
      phenotypic phases in Bordetella pertussis. The proposed model identifies a novel
      mechanism of transcriptional interference between two promoters present in the
      bvg locus. To understand the system behavior under elevated temperature, the
      developed model has been studied in two different ways. First, a quasi-steady
      state analysis has been carried out for the two component system, comprising of
      sensor BvgS and response regulator BvgA. The quasi-steady state analysis reveals
      temperature induced sharp molecular switch, leading to amplification in the
      output of BvgA. Accumulation of a large pool of BvgA thus results into
      differential regulation of the downstream genes, including the gene encoding
      toxin. Numerical integration of the full network kinetics is then carried out to
      explore time dependent behavior of different system components, that
      qualitatively capture the essential features of experimental results performed in
      vivo. Furthermore, the developed model has been utilized to study mutants that
      are impaired in their ability to phosphorylate the transcription factor, BvgA, of
      the signaling network.

PMID- 22960293
TI  - Degradable starch microspheres transarterial chemoembolisation (DSM-TACE) of HCC:
      Dynamic Contrast-Enhanced Ultrasonography (DCE-US) based evaluation of
      therapeutic efficacy using a novel perfusion software.
AB  - PURPOSE: To evaluate therapeutic efficacy of degradable starch microsphere (DSM)
      TACE in hepatocellular carcinoma (HCC) using Dynamic Contrast-Enhanced
      Ultrasonography (DCE-US) based perfusion analysis. MATERIALS AND METHODS: A total
      of 60 DCE-US examinations were performed in 15 selected patients who underwent
      DSM-TACE with EmboCept(r)S for the treatment of advanced HCC. DCE-US was
      performed via i.v. application of ultrasound contrast media before and 24 hours
      post embolization. In addition DCE-US was performed with i.a. contrast
      application via the angiographic catheter right before and after the
      embolization. Microcirculation of embolized HCC lesions was quantified using a
      dedicated perfusion software by two experienced radiologists in consensus.
      RESULTS: Significant reduction of microvascularization (PE, WiAUC and WiR) was
      seen right after DSM-TACE and during 24 hour follow-up. Mean PE was 342.22 +/-
      97.80 prior to embolization, 59.28 +/- 29.74 post embolization (p = 0.019) and
      18.83 +/- 7.03 during follow-up (p <= 0.01). Mean WiAUC was 1103.21 +/- 432.05
      prior to embolization 267.69 +/- 151.80 post embolization (p = 0.023) and 105.10
      +/- 44.43 during 24 hour follow-up (p <= 0.01). The corresponding values for WiR
      were 224.91 +/- 57.97 prior-, 38.14 +/- 18.80 post embolization (p = 0.034) and
      6.97 +/- 2.68 during follow up (p <= 0.01). CONCLUSION: In this study,
      therapeutic efficacy of DSM-TACE in HCC using DCE-US based perfusion analysis
      could be demonstrated.

PMID- 22960294
TI  - Ultrasound image fusion - clinical implementation and potential benefits for
      monitoring of renal transplants.
AB  - PURPOSE: To evaluate the feasibility of US image fusion in the clinical routine
      and to discuss potential benefits for follow-up after renal transplantation.
      MATERIALS AND METHODS: 15 patients with a renal transplant were prospectively
      included in the study. For all of them, a previously performed CT- or MRI-scan
      covering the renal transplant was available. Each patient was investigated using
      ultrasound image fusion. Time needed for sucessful implementation of image fusion
      was registered. Subsequently, quality of image fusion was assessed by two
      experienced radiologists (10 and 5 years of experience) in consensus using a
      subjective 5 point rank scale (1 = best). RESULTS: Image fusion was successfully
      performed in all patients. Time needed for setup of image fusion varied from 45
      120 sec (85 +/- 5 sec). The score for quality of US image fusion was 1.9 +/- 0.7.
      CONCLUSION: Assessment of renal transplants using US image fusion is feasible and
      provides several potential benefits for the follow-up of renal transplants.

PMID- 22960295
TI  - Fibrinogen interaction with the red blood cell membrane.
AB  - A brief review of the fibrinogen molecule composition and structure is presented
      like as an introduction to the effects of this plasma protein on the red blood
      cell hemorheoplogical properties namely erythrocyte aggregation tendency and
      deformability ability. The protein membrane RBC target for fibrinogen is also
      highlight as well as the erythrocyte signal transduction pathway associated with
      nitric oxide mobilization resulting from its binding.

PMID- 22960296
TI  - Comparison of consecutive bolus tracking and flash replenishment measurements for
      the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS)
      in an experimental human squamous cell carcinoma model.
AB  - PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the
      assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an
      experimental small-animal-squamous-cell-carcinoma-model. Since the underlying
      tissue is the same, strong correlations between parameter outcomes of both
      techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells
      were subcutaneously injected into the left flank of 18 female athymic-nude-rats.
      After 10 days of subcutaneous tumour growth, bolus tracking and flash
      replenishment measurements were performed consecutively in the same imaging plane
      in each rat after bolus-injection of SonoVue via the lateral tail vein using a
      high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed
      with dedicated software (VueBox(r), Bracco-Suisse(r)). From BT measurements, the
      parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean
      transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were
      derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time
      MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats,
      BT and FR measurements could be completed successfully. Highly significant
      correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and
      MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT,
      rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and
      WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a
      wide range of modalities including CEUS, CT and MR, FR as a technique for the
      assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield
      different parameters, the underlying tissue hemodynamics are equal. In this work,
      we were able to demonstrate strong correlations between different parameters of
      both modalities in a small-animal-tumor-model, indicating that flash
      replenishment is a valid alternative to the more established bolus-tracking
      technique. Although the lack of absolute, quantitative parameters hinders a
      direct comparison of both modalities, FR and BT should both be suitable for a
      relative comparison, e.g. between baseline and follow-up examinations.

PMID- 22960297
TI  - Influence of systemic hypothermia on the myocardial oxygen tension during
      extracorporeal circulation: comparative study in German Landrace pigs.
AB  - During extracorporeal circulation (ECC) controlled hypothermia is a common method
      of myocardial protection due to a reduction of the myocardial oxygen consumption.
      Although the beneficial aspects of hypothermia on the myocardial metabolism have
      been widely demonstrated the effect of hypothermia on the myocardial oxygen
      tension (PmyO2) is unclear. For this reason the PmyO2 of German Landrace pigs
      (male, three months of age) during ECC was analysed under mild hypothermia (32
      degrees C, n = 6 pigs) and under normothermia (n = 10 pigs, control group) within
      a time period of 23 min (1400 sec). Flexible invasive Clark type microcatheters
      were used to measure the PmyO2 in the beating heart. During normothermal ECC a
      continuous PmyO2 increase from 36.5 +/- 15.8 mmHg to 52.6 +/- 27.2 mmHg (+44.1%)
      after 1400 sec was measured (p = 0.02). In contrast, mild hypothermia caused a
      continuous PmyO2 decrease from initially 46.9 +/- 17.5 mmHg to 36.7 +/- 20.8 mmHg
      (-21.8%, p < 0.013) in the test period. Electrocardiography revealed no signs of
      ischemia or arrhythmia during normo- and hypothermic ECC. It seems obvious that
      mild hypothermia results in a reduction of the oxygen transfer to the myocardial
      cells and that this effect outweighs the beneficial effects of hypothermia in the
      myocardium which are related to reduced oxygen consumption. However, in mild
      hypothermia oxygen supply to the myocardium remained sufficient for normal
      myocardial function.

PMID- 22960298
TI  - Mandibular reconstruction with microvascular re-anastomosed fibular free flaps -
      two complementary methods of postoperative transplant monitoring.
AB  - PURPOSE: Evaluation of two complementary methods, i.e. luminescence ratiometric
      oxygen imaging (LROI) and contrast-enhanced ultrasound (CEUS) for postoperative
      evaluation of the perfusion of osseocutaneous fibular free flaps used for
      mandibular reconstructions. PATIENTS AND METHODS: 15 patients with microvascular
      re-anastomosed osseocutaneous fibular flaps were included in this trial.
      Perfusion of the cutaneous part of the flap was determined by measuring a
      fluorescent oxygen sensor foil covering the flap's skin surface with a handheld
      fluorescence-microscope. The sensor contains a reservoir of oxygen that is
      consumed by the tissue, which corresponds to the perfusion status of a flap.
      Measurements were done before explantation, after successful anastomosis and 1
      day after surgery. Additionally, flap perfusion was qualitatively evaluated by
      contrast-enhanced ultrasound (CEUS) in 13 out of 15 patients. Ultrasound
      examinations were carried out with a high resolution linear probe after an
      intravenous bolus injection of 2.4 ml SonoVue(r) within the first 14 days after
      surgery. RESULTS: Out of the 15 harvested and transplanted flaps, 3 showed
      microcirculatory problems on the first postoperative day. All complications were
      detected by LROI prior to clinical signs. For LROI, we were able to confirm the
      threshold slope value of 0.3 for differentiating between well perfused and
      compromised flaps as suggested in our previous study. CEUS showed qualitatively
      detectable bone perfusion in the 13 measured flaps. 2 flaps that were lost on the
      second and third postoperative day were also lost for CEUS control. The flap
      survival rate was 87%, and the complication rate was 33%. CONCLUSION: LROI has
      been proven to deliver reproducible objective results for monitoring cutaneous
      flaps. In addition, CEUS is a promising method for evaluating the
      microcirculation of the deeper parts (such as bone) of osseocutaneous flaps. Both
      methods supplement each other, thus allowing the monitoring of all levels of
      osseocutaneous flaps.

PMID- 22960299
TI  - Evidence of a weak correlation between peripheral endothelial function measures
      and carotid intima-media thickness.
AB  - Previous studies from our and other laboratories have demonstrated the existence
      of a clear relationship between different measures of endothelial function and
      the extent of coronary atherosclerosis. The relationship between endothelial
      function and carotid intima-media thickness has not been extensively
      investigated. Endothelial function using radial artery flow-mediated constriction
      (L-FMC) and dilation (FMD) was assessed in 513 consecutive patients undergoing
      diagnostic coronary angiography. Intima-media thickness of both carotid arteries
      was also measured. IMT was greater in patients with diabetes, males, those with
      body mass index >30, and in those older than 65 years (all p < 0.05). There was a
      strong correlation between age and IMT (p < 0.0001). Hypercholesterolemia and a
      family history for cardiovascular disease had no impact on IMT. In contrast, the
      relationship between either L-FMC or FMD and IMT was weak at best (p = 0.008 for
      the relationship between L-FMC and IMT, p = 0.13 for the relationship between FMD
      and IMT). There was a positive correlation between IMT and resting radial artery
      diameter (p = 0.008). IMT increased with the extent of coronary artery disease,
      but this trend did not reach statistical significance (p = 0.07). Resting (L
      FMC), but not recruitable (FMD) endothelial function correlates with the extent
      of subclinical carotid atherosclerosis. This correlation is however weaker in
      comparison to that with age.

PMID- 22960300
TI  - Image fusion in the management of thermal tumor ablation of the liver.
AB  - PURPOSE: The purpose of this study was to evaluate whether image fusion with
      contrast enhanced ultrasound (CEUS) and CT is effective in the pre-, intra- and
      post-interventional management of liver lesions during microwave or
      radiofrequency ablation. METHODS AND MATERIALS: Fifteen patients with a single
      hepatocellular carcinoma (HCC) up to 3 cm diameter, identified on both contrast
      enhanced CT (Siemens Somatom Definition AS and Definition Edge, Siemens
      Healthcare, Erlangen, Germany) and ultrasound (Siemens ACUSON S2000TM or S3000TM,
      Siemens Healthcare, Erlangen, Germany) were retrospectively enrolled between July
      2011 and May 2012. Either automatic registration or plane match registration was
      chosen on CT and ultrasound for the pre-, intra- and postinterventional
      management of all treated liver lesions during microwave or radiofrequency
      ablation. Using conventional ultrasound B-mode, CEUS and image fusion including B
      mode and CEUS the detectability of the liver lesions was evaluated semi
      quantitatively by comparing the image sequences in a consensus reading. Eight
      patients underwent radiofrequency ablation and seven patients underwent microwave
      ablation. RESULTS: All patients were examined using all diagnostic ultrasound
      tools of the study. The results show that the procedure is easy and convenient to
      perform, as well as efficient. The co-registration procedure took approximately 5
      to 10 minutes depending on the amount of DICOM volume-data and the habitus of the
      patient. The results show that the use of image fusion with CT and contrast
      enhanced ultrasound could improve the diagnostic assessment capabilities in
      comparison to the examination without image fusion in the pre-, intra- and
      postinterventional management of malignant liver lesions during thermal ablation.
      CONCLUSION: Percutaneous thermal ablation guided by contrast-enhanced ultrasound
      and image fusion seems to be an efficient approach for malignant liver lesions
      especially if these are not clearly demarcated by B-mode. The use of the image
      fusion technique in the pre-, intra- and postinterventional management can
      increase operator confidence, the accuracy of the procedure, and technical
      success in real time.

PMID- 22960301
TI  - Postoperative evaluation of microvascularization in mandibular reconstructions
      with microvascular flaps - first results with a new perfusion software for
      contrast-enhanced sonography (CEUS).
AB  - PURPOSE: Quantitative measurement of dynamic contrast values obtained by contrast
      enhanced ultrasound (CEUS) for evaluating microvascularization in osseous and
      osseocutaneous free flaps used for maxillofacial reconstructions. PATIENTS AND
      METHODS: 22 patients (6 women, 16 men, mean age: 57 years, range: 47 to 82 years)
      who had received mandibular reconstructions with 3 avascular and 19 microvascular
      free osseous or osseocutaneous transplants were included in this trial. 16
      patients had received a microvascular osseocutaneous fibular flap, 2 patients a
      microvascular osseous fibular flap and 1 patient a microvascular osseous iliac
      crest flap. Patients were followed up for 12 months on average (range: 3 to 20
      months). Ultrasound examination was carried out by one experienced examiner with
      a linear probe (6-9 MHz, LOGIQ E9, GE) after the intravenous bolus injection of
      2.4 ml contrast agent (SonoVue(r), BRACCO, Germany). Digital cine loops were
      analysed with a quantification software (VueBoxTM) for determining wash-in
      parameters: Rise Time (RT), Peak Enhancement (PE), Wash-in Area Under the Curve
      (WiAUC) and Wash-in Rate (WiR). Results were compared with the patients'
      postoperative clinical outcome. RESULTS: For the bone area the median of the RT
      was 10.0 s (range 3.1 to 65.0 s), for the ratio between bone tissue and soft
      tissue for the PE the median was 10.4% (range 2.6 to 29.8%), the median for the
      WiAUC was 11.1% (range 1.5 to 77.7%) and the median for the WiR was 5.7 %(range
      0.7 to 61.1%). None of the patients with microvascular osseocutaneous and osseous
      flaps showed any signs of transplant bone loss, which corresponded with the
      qualitative CEUS assessment. The patients with microvascular re-anastomosed
      transplants showed widely varying values for the investigated parameters (RT, PE,
      WiAUC, WiR). For patients with avascular bone transplants, these parameters were
      reduced to zero values for the bone area resulting in a significant difference (p
      < 0.05) for the PE compared to the patients with microvascular bone transplants.
      CONCLUSION: CEUS allowed the qualitative assessment of bone microvascularization
      by observing the transition of the contrast agent from the periostal area into
      the bone. However, defining a critical lower border by quantification of bone
      perfusion was difficult because of the inconstant perfusion of the bone
      transplants used in the trial.

PMID- 22960302
TI  - Parameters of blood viscosity do not correlate with the extent of coronary and
      carotid atherosclerosis and with endothelial function in patients undergoing
      coronary angiography.
AB  - While the role of physical forces on the control of atherogenesis and the
      modulation of endothelial function is well known, studies investigating the
      impact of shear stress on the extent of central atherosclerosis and flow-mediated
      dilation in humans produced controversial results. We investigated the
      relationship between viscosity, coronary atherosclerosis, carotid intima-media
      thickness and flow-mediated dilation in patients undergoing coronary angiography.
      451 patients (306 males, mean age 66 +/- 10) were enrolled. Viscosity, which was
      calculated using a validated formula, showed a positive association with platelet
      activation (P = 0.01), leukocyte counts (P = 0.006) and C-reactive protein (P =
      0.03), a marker of inflammation; surprisingly, visocsity showed a negative
      association with FMD (FMD decreased 0.14 +/- 0.05% per each cPoise increase in
      viscosity) but only in patients without coronary artery disease. Viscosity showed
      no association with the extent of coronary or carotid artery disease. We provide
      cross-sectional data on the relationship between whole blood viscosity and
      parameters of vascular structure and function. While viscosity correlated with
      parameters of vascular inflammation, it showed no relationship with the presence
      and severity of central atherosclerosis.

PMID- 22960303
TI  - The influence of poly(n-butyl acrylate) networks on viability and function of
      smooth muscle cells and vascular fibroblasts.
AB  - BACKGROUND: The patency of small-diameter vascular prostheses is limited by
      several factors such as thrombogenicity, which is strongly influenced by surface
      roughness and chemical composition, or a mechanical mismatch between the elastic
      modulus of an artery and of the vascular prosthesis. A confluent layer of
      endothelial cells onto the inner surface of vascular prostheses could improve the
      hemocompatibility of the device. Biomaterials with adjustable elastic properties
      could be tailored to the values of human arteries so that a prothesis mismatch
      could be avoided. It was recently demonstrated that a co-culture of endothelial
      cells with angiogenically stimulated monocytes (aMO2) shows an accelerated
      formation of a functional confluent endothelial cell monolayer on soft
      hydrophobic poly(n-butyl acrylate) (cPnBA) networks. In addition, the cell
      compatibility with vascular smooth muscle cells and aortic fibroblasts, which are
      other important cell types of the vessel wall, is essential for a vascular
      prosthesis material and must therefore be explored. PURPOSE: Here we investigated
      the interaction of human vascular smooth muscle cells and aortic fibroblasts with
      cPnBA04 and cPnBA73. MATERIAL AND METHODS: Human primary vascular smooth muscle
      cells and aortic fibroblasts were seeded on the two cPnBAs with different elastic
      moduli (cPnBA04 - 250 kPa and cPnBA73 - 1100 kPa) over 72 h. A live-dead staining
      (fluorescein diacetate/propium iodide) was performed to determine the morphology
      and viability of adherent cells. Furthermore, the extracellular matrix
      components, the actin cytoskeleton, the cell-material-contacts and the cytokine
      profiles were analysed. RESULTS: Both cell types adhered and were viable on
      cPnBA04 and cPnBA73. The level of pro-inflammatory cytokine secretion (IFN-gamma
      and TNF-alpha) by smooth muscle cells and vascular fibroblasts was comparable to
      that of cells cultivated on a control material. The release of these cytokines by
      human fibroblasts was higher on cPnBA73 compared to cPnBA04. Both cell types
      secreted an extracellular matrix comparable to cells seeded on a control
      material. CONCLUSION: The study revealed, that cPnBA with varying elastic moduli
      are not only suitable for the cultivation of endothelial cells, but also for
      human vascular smooth muscle cells and aortic fibroblasts. Therefore, cPnBA could
      be a potential candidate material for the development of cardiovascular
      prostheses.

PMID- 22960304
TI  - Pasireotide (SOM230) protects the retina in animal models of ischemia induced
      retinopathies.
AB  - The neuropeptide somatostatin and selective analogs for the sst(2/5) receptor
      subtypes provided neuroprotection against retinal chemical ischemia ex vivo and
      AMPA [(RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide]
      induced retinal toxicity in vivo, when employed in micromolar concentrations
      (Mastrodimou et al., 2005; Kiagiadaki and Thermos, 2008). The aim of the present
      study was to investigate the neuroprotective properties of a new metabolically
      stable agent pasireotide (SOM230) in the above mentioned retinal models of
      ischemia. Adult Sprague Dawley (250-350 g) rats were employed. For the ex vivo
      experiments, retinal eye cups were incubated with PBS or the chemical ischemia
      mixture [iodoacetic acid (5 mM)/sodium cyanide (25 mM)] in the absence or
      presence of SOM230 (10(-7)-10(-5) M) alone or in the presence of the sst(2)
      antagonist CYN-154806 (10(-7) or 10(-5) M). In the in vivo model, the animals
      received intravitreally: PBS (50 mM), AMPA (42 nmol/eye) or AMPA (42 nmol) in
      combination with SOM230 (10(-7)-10(-5) M). Immunohistochemistry studies using
      antisera against bNOS, a marker for brain/neuronal NOS containing amacrine cells,
      protein kinase C (PKC) a marker for rod bipolar cells, and TUNEL studies in
      conjunction with FACS analysis were employed to examine retinal cell loss and
      protection. Chemical ischemia led to a loss of bNOS and PKC immunoreactivity
      which was reversed by SOM230. Partial and full protection of bNOS and PKC
      immunoreactive neurons, respectively, was observed even at the low concentration
      of 10(-7) M. The neuroprotective actions of SOM230 (10(-7) or 10(-5) M) were
      reversed by CYN-154806 (10(-7) or 10(-5) M, respectively). Similarly, SOM230 (10(
      7), 10(-6), 10(-5) M) provided neuroprotection in the in vivo model. The dose of
      10(-7) M prevented the loss of the bNOS cells and provided almost full
      protection. These data were substantiated by TUNEL staining and fluorescence
      activated cell sorting (FACS) analysis. SOM230 appears very efficacious in its
      neuroprotective properties in both models of retinal ischemia affording
      neuroprotection at the concentration or dose of 100 nM. These data suggest that
      SOM230 might represent a useful pharmacological compound for the treatment of
      retinal disease.

PMID- 22960305
TI  - Effect of garlic-derived organosulfur compounds on mitochondrial function and
      integrity in isolated mouse liver mitochondria.
AB  - The objectives of this work were to evaluate the direct effects of diallysulfide
      (DAS) and diallyldisulfide (DADS), two major organosulfur compounds of garlic
      oil, on mitochondrial function and integrity, by using isolated mouse liver
      mitochondria in a cell-free system. DADS produced concentration-dependent
      mitochondrial swelling over the range 125-1000MUM, while DAS was ineffective.
      Swelling experiments performed with de-energized or energized mitochondria showed
      similar maximal swelling amplitudes. Cyclosporin A (1MUM), or ethylene glycol
      bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 1mM) were ineffective in
      inhibiting DADS-induced mitochondrial swelling. DADS produced a minor (12%)
      decrease in mitochondrial membrane protein thiols, but did not induce clustering
      of mitochondrial membrane proteins. Incubation of mitochondria with DADS (but not
      DAS) produced an increase in the oxidation rate of 2',7' dichlorofluorescein
      diacetate (DCFH-DA), together with depletion of reduced glutathione (GSH) and
      increased lipid peroxidation. DADS (but not DAS) produced a concentration
      dependent dissipation of the mitochondrial membrane potential, but did not induce
      cytochrome c release. DADS-dependent effects, including mitochondrial swelling,
      DCFH-DA oxidation, lipid peroxidation and loss of mitochondrial membrane
      potential, were inhibited by antioxidants and iron chelators. These results
      suggest that DADS causes direct impairment of mitochondrial function as the
      result of oxidation of the membrane lipid phase initiated by the GSH- and iron
      dependent generation of oxidants.

PMID- 22960306
TI  - Effects of Fastac 50 EC on bumble bee Bombus terrestris L. respiration: DGE
      disappearance does not lead to increasing water loss.
AB  - Sublethal effects of pesticides in insects can be observed through physiological
      changes, which are commonly estimated by metabolic rate and respiratory patterns,
      more precisely by the patterns of discontinuous gas-exchange (DGE) cycles. The
      aim of the present research was to study the effect of some low concentrations of
      Fastac 50 EC on the cycles of CO(2) release and respiratory water loss rates
      (WLR) in bumble bee Bombus terrestris L. foragers. Bumble bees were dipped into
      0.004% and 0.002% Fastac 50 EC solution. Flow-through respirometry was used to
      record the respiration and WLR 3h before and after the treatment. The
      respirometry was combined with infrared actography to enable simultaneous
      recording of abdominal movements. Our results show that Fastac 50 EC has an after
      effect on bumble bee respiratory rhythms and muscle activity but does not affect
      WLR. Treatment with 0.004% Fastac 50 EC solution resulted in disappearance of the
      respiration cycles; also the lifespan of treated bumble bees was significantly
      shorter. Treatment with 0.002% Fastac 50 EC solution had no significant effect on
      respiration patterns or longevity. We found no evidence for the DGE cycles
      functioning as a water saving mechanism.

PMID- 22960308
TI  - Oral delivery of anticancer drugs II: the prodrug strategy.
AB  - Many anticancer drugs are sparingly water soluble and they show a low
      permeability at the intestinal level. Furthermore, their oral bioavailability is
      impaired because they are substrates of the cytochrome P450 and of the efflux
      pumps. The prodrug strategy, which is discussed in the present review, represents
      one of the different approaches to overcome these obstacles. In this review, we
      highlight the progresses of clinical development in the prodrug area for the oral
      administration of anticancer drugs.

PMID- 22960309
TI  - In vitro and in vivo genotoxicity of silver nanoparticles.
AB  - The biocidal effect of silver nanoparticles (Ag-np) has resulted in their
      incorporation into consumer products. While the population exposed to Ag-np
      continues to increase with ever new applications, Ag-np remains a controversial
      research area with regard to their toxicity in biological systems. Here a
      genotoxic and cytotoxic approach was employed to elucidate the activity of Ag-np
      in vitro and in vivo. Characterization of Ag-np using scanning electron
      microscopy revealed a size range of 90-180nm. Cytotoxic potential of Ag-np was
      evaluated in human lymphocytes via cell viability assay (Trypan blue dye
      exclusion method, MTT and WST assay). The uptake and incorporation of Ag-np into
      the lymphocytes was confirmed by flow cytometry. Additionally apoptosis (AnnexinV
      FITC-PI staining) and DNA strand breaks (comet assay) in human lymphocytes
      revealed that Ag-np at concentration 25MUg/ml can cause genotoxicity. In vivo
      experiments on plants (Allium cepa and Nicotiana tabacum) and animal (Swiss
      albino male mice) showed impairment of nuclear DNA. Induction of oxidative stress
      was also studied. The DNA damage and chromosomal aberrations raise the concern
      about the safety associated with applications of the Ag-np. A single ip
      administration of Ag-np gave a significant (P<=0.05) increase in the frequency of
      aberrant cells and Tail DNA percent at concentrations 10mg/kg body weight and
      above. Results of comet assay in A. cepa and N. tabacum demonstrated that the
      genotoxic effect of Ag-np was more pronounced in root than shoot/leaf of the
      plants. The present study indicated a good correlation between the in vitro and
      in vivo experiments. Therefore the biological applications employing Ag-np should
      be given special attention besides adapting the antimicrobial potential.

PMID- 22960307
TI  - The roles of serpins in mosquito immunology and physiology.
AB  - In vector-borne diseases, the complex interplay between pathogen and its vector's
      immune system determines the outcome of infection and therefore disease
      transmission. Serpins have been shown in many animals to be key regulators of
      innate immune reactions. Their control over regulatory proteolytic cascades
      ultimately decides whether the recognition of a pathogen will lead to an
      appropriate immune response. In mosquitoes, serpins (SRPNs) regulate the
      activation of prophenoloxidase and thus melanization, contribute to malaria
      parasite lysis, and likely Toll pathway activation. Additionally, in culicine
      mosquitoes, SRPNs are able to regulate hemostasis in the vertebrate host,
      suggesting a crucial role during bloodfeeding. This review summarizes the
      annotation, transcriptional regulation, and current knowledge of SRPN function in
      the three mosquito species for which the complete genome sequence is available.
      Additionally, we give a brief overview of how SRPNs may be used to prevent
      transmission of vector-borne diseases.

PMID- 22960310
TI  - Patterns of the UP-Down state in normal and epileptic mice.
AB  - Goal of this manuscript is to investigate whether changes that exist in epileptic
      brain generating spontaneous seizures are reflected in the pattern of the UP-Down
      state (UDS) recorded from the neocortex and dentate gyrus. Experiments were
      carried out on naive and epileptic mice under urethane anesthesia. Local field
      potentials were recorded with chronically implanted microelectrodes and single
      unit activity was recorded with glass microelectrodes. Recorded neurons were
      labeled by neurobiotin and identified later as granular cells or interneurons in
      histological sections. The following major features differentiate the pattern of
      UDS in epilepsy from normal. (1) The duration of UP and Down phases is
      significantly longer. (2) Recovery of network excitability after termination of
      the UP phase is longer. (3) UP-spikes occur during the UP phase, which
      transiently interrupt the development of the normal electrographic pattern of UP
      phase. Our data provide evidence that UP-spikes result from gigantic EPSPs
      generated in response to afferent activity. UP-spikes in the neocortex and
      dentate gyrus occur in close temporal relationship indicating the existence of
      direct or indirect pathological functional connections between these areas.
      Changes in the duration of UP and Down phases as well increased time of recovery
      of excitability of epileptic brain after termination of UP phase suggest
      alterations in the homeostatic properties of neuronal network in epileptic brain.
      We suggest that the existence of UP-spikes in epileptic brain may be an
      additional electrographic pattern indicating epileptogenicity. Unraveling the
      neuronal substrates of UP-spikes may further improve our understanding of the
      mechanisms of epilepsy.

PMID- 22960312
TI  - Early-life citalopram-induced impairments in sexual behavior and the role of
      androgen receptor.
AB  - Postnatal treatment with selective serotonin reuptake inhibitors (SSRIs) has been
      found to affect brain development and the regulation of reproduction in rodent
      models. The normal masculinization process in the brain requires a transient
      decrease in serotonin (5-HT) levels in the brain during the second postnatal
      week. Strict regulation of androgen receptor (AR) and gonadotropin-releasing
      hormone (GnRH) expression is important to control male reproductive activity.
      Therefore, this study was designed to examine the effects of a potent SSRI
      (citalopram) on male sexual behavior and expression levels of AR and GnRH in
      adult male mice receiving either vehicle or citalopram (10mg/kg) daily during
      postnatal days 8-21. The citalopram-treated male mice showed altered sexual
      behavior, specifically a significant reduction in the number of intromissions
      preceding ejaculation compared with the vehicle-treated mice. The citalopram
      treated male mice displayed elevated anxiety-like behavior in an open field test
      and lower locomotor activity in their home cage during the subjective night.
      Although there was no change in GnRH and AR mRNA levels in the preoptic area
      (POA), quantified by real-time polymerase chain reaction, immunostained AR cell
      numbers in the medial POA were decreased in the citalopram-treated male mice.
      These results suggest that the early-life inhibition of 5-HT transporters alters
      the regulation of AR expression in the medial POA, likely causing decreased
      sexual behavior and altered home cage activity in the subjective night.

PMID- 22960311
TI  - Morphological and genetic activation of microglia after diffuse traumatic brain
      injury in the rat.
AB  - Traumatic brain injury (TBI) survivors experience long-term post-traumatic
      morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to
      whisker stimulation models the agitation of TBI survivors and provides anatomical
      landmarks across the whisker-barrel circuit to evaluate post-traumatic
      neuropathology. As a consequence of TBI, acute and chronic microglial activation
      can contribute to degenerative and reparative events underlying post-traumatic
      morbidity. Here we hypothesize that a temporal sequence of microglial activation
      states contributes to the circuit pathology responsible for post-traumatic
      morbidity, and test the hypothesis by examining microglial morphological
      activation and neuroinflammatory markers for activation states through gene
      expression and receptor-binding affinity. Adult male, Sprague-Dawley rats were
      subjected to a single moderate midline fluid percussion injury (FPI) or sham
      injury. Microglial activation was determined by immunohistochemistry,
      quantitative real-time PCR and receptor autoradiography in the primary
      somatosensory barrel field (S1BF) and ventral posterior medial nucleus (VPM) of
      the thalamus at 7 and 28 days following FPI. Morphological changes indicative of
      microglial activation, including swollen cell body with thicker, shrunken
      processes, were evident in S1BF and VPM at 7 and 28 days post-injury. Principally
      at 7 days post-injury in VPM, general inflammatory gene expression (major
      histocompatibility complex I, major histocompatibility complex II, translocator
      protein 18 kDa [TSPO]) is increased above sham level and TSPO gene expression
      confirmed by receptor autoradiography. Further, CD45, a marker of classical
      activation, and TGF-betaI, an acquired deactivation marker, were elevated
      significantly above sham at 7 days post-injury. Daily administration of the anti
      inflammatory ibuprofen (20mg/kg, i.p.) significantly reduced the expression of
      these genes. Evidence for alternative activation (arginase 1) was not observed.
      Thus, these data demonstrate concomitant classical activation and acquired
      deactivation phenotypes of microglia in diffuse TBI in the absence of overt
      contusion or cavitation. Anti-inflammatory treatment may further alleviate the
      neuropathological burden of post-traumatic inflammation.

PMID- 22960313
TI  - An in vitro approach to assess the neurotoxicity of valproic acid-induced
      oxidative stress in cerebellum and cerebral cortex of young rats.
AB  - Valproic acid (VPA), a branched short-chain fatty acid, is generally used as an
      antiepileptic drug and a mood stabilizer. VPA is a relatively safe drug, but its
      use in higher concentrations is associated with idiosyncratic neurotoxicity.
      Investigations involving cerebral cortex and cerebellum can shed light on whether
      neurotoxicity induced by branched chain fatty acids like VPA is mediated by
      oxidative stress. The aim of our investigation was to evaluate the neurotoxic
      potential of VPA by using preparation of cerebral cortex and cerebellum of young
      rats as an in vitro model. Oxidative stress indexes such as lipid peroxidation
      (LPO) and protein carbonyl (PC) formation were evaluated to visualize whether the
      first line of defence was breached. The levels of oxidative stress markers, LPO
      and PC were significantly elevated. Non-enzymatic antioxidants' effect was also
      demonstrated as a significant depletion in reduced glutathione (GSH) and non
      protein thiol activity (NP-SH), but there was no significant increase or decrease
      in the concentrations of total thiol (T-SH) and protein thiol (P-SH). VPA also
      showed significant reduction in the activities of glutathione metabolizing
      enzymes such as glutathione-S-transferase (GST), glutathione reductase (GR) and
      glutathione peroxidase (GPx) and other antioxidant enzymes like superoxide
      dismutase (SOD), catalase (CAT) in cerebellum and cerebral cortex. A significant
      elevation was also observed in the activity of xanthine oxidase (XO). Some
      neurotoxicity biomarkers were investigated in which the activity of
      acetylcholinesterase (AChE) and sodium-potassium ATPase (Na(+), K(+)-ATPase) was
      decreased and monoamine oxidase (MAO) was increased. These results indicate that
      VPA induces oxidative stress by compromising the antioxidant status of the
      neuronal tissue. Further studies are required to decipher the cellular and
      molecular mechanisms of branched chain fatty acid-induced neurotoxicity.

PMID- 22960315
TI  - The influence of attention levels on psychophysiological responses.
AB  - This study aimed to examine which brain oscillatory activities and peripheral
      physiological measures were influenced by attention levels. A new experimental
      procedure was designed. Participants were asked to count the number of target
      events while viewing eight moving white circles. An event occurred when two of
      the circles changed from white to red or blue. In the low-attention task, similar
      to a feature search, the target events were defined by color only. In the high
      attention task, similar to a conjunction search, the target events were defined
      by both color and size. In the control task, participants were asked to passively
      watch the series of events while remembering a number. Based on Feature
      Integration Theory, our high-attention task would demand more attentional
      investment than the low-attention task. Given the identical visual stimuli and
      requirement of keeping a number in working memory for all three tasks, the
      changes in brain oscillatory activities can be attributed to attention level
      rather than to perceptual content or memory processes. Peripheral measures such
      as heart rate, heart rate variability (HRV), respiration rate, eye blinks, and
      skin conductance level were also evaluated. In comparing the high-attention task
      with the low-attention task, theta synchronization at the Fz, Cz, and Pz
      electrodes as a group, alpha2 desynchronization at the Fz, Cz, Pz, and Oz
      electrodes as a group, and a decrease in the low-frequency component and ratio
      measure of HRV were evident. These measures are considered to be promising
      indices for discriminating between attention levels.

PMID- 22960314
TI  - Parkin prevents cortical atrophy and Abeta-induced alterations of brain
      metabolism: 13C NMR and magnetic resonance imaging studies in AD models.
AB  - Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized by
      extracellular Abeta plaques and intraneuronal neurofibrillary tangles. We
      conducted longitudinal studies to examine the effects of Abeta on brain amino
      acid metabolism in lentiviral Abeta(1-42) gene transfer animals and transgenic AD
      mice. We also performed lentiviral parkin gene delivery to determine the effects
      of Abeta clearance in AD models. Abeta(1-42) activated mTOR signaling, and
      increased 4E-BP phosphorylation. Abeta(1-42) increased the synthesis of glutamate
      and aspartate, but not glutamine, leucine and isoleucine, but an increase in
      leucine and isoleucine levels was concurrent with diminution of
      neurotransmitters. Additionally, Abeta(1-42) attenuated mitochondrial
      tricarboxylic acid (TCA) cycle activity and decreased synthesis of its by
      products. Glutamate levels increased prior to lactate accumulation, suggesting
      oxidative stress. Importantly, parkin reversed the effects of Abeta(1-42) on
      amino acid levels, prevented TCA cycle impairment and protected against glutamate
      toxicity. Cortical atrophy was observed in aged 3xTg-AD mice, while parkin
      expression was associated with reduced atrophy. Similarly, Abeta(1-42) resulted
      in significant cell loss, pronounced astrogliosis and cortical atrophy and parkin
      reduced astrogliosis and reversed Abeta(1-42) effects on cell loss and cortical
      atrophy. Taken together these data suggest that parkin prevents amyloid-induced
      alteration of brain metabolism and may be used as a therapeutic target to limit
      neuronal loss in AD.

PMID- 22960316
TI  - Intraocular pressure magnitude and variability as predictors of rates of
      structural change in non-human primate experimental glaucoma.
AB  - The purpose of this study is to determine the effects of intraocular pressure
      (IOP) mean, maximum and variability on the rate of structural change in
      experimental glaucoma. Data were taken retrospectively from 59 non-human primates
      involved in ongoing studies of experimental glaucoma. IOP was measured by
      tonometry every 1-3 weeks, and these readings split into non-overlapping fixed
      length windows. First, different characterizations of IOP variability were tested
      to find the one that was least correlated with the mean IOP within the same
      window. Next, the rates of change of the Mean Position of the Disc (MPD) from
      confocal scanning laser tomography, and Retinal Nerve Fiber Layer Thickness
      (RNFLT) from spectral domain ocular coherence tomography, were calculated over
      each window. Mixed effects models were formed to predict these rates based on the
      characterizations of IOP. Normalized root mean squared residual (RMSR) from the
      trend of IOP during windows of five IOP measurements provided a characterization
      of variability showing lowest correlation with mean IOP (r < 0.001). In
      univariate analyses, rate of change of MPD and RNFLT were predicted by mean IOP
      (p < 0.001 for both) and maximum IOP (p < 0.001 for both). IOP variability did
      not significantly predict change in MPD (p = 0.129) or RNFLT (p = 0.438). In
      bivariate models, maximum IOP was the most significant predictor of change. We
      conclude that normalized RMSR allows the effects of IOP variability to be
      assessed independently of mean IOP. Maximum IOP provided the best predictability
      of structural change, either causally or because it captures the contributions of
      both mean and variability.

PMID- 22960317
TI  - Ambient illuminance, retinal dopamine release and refractive development in
      chicks.
AB  - Form deprivation and low illuminance of ambient light are known to induce myopia
      in chicks. Low concentrations of retinal dopamine, a light-driven neurohormone,
      was previously shown to be associated with form deprivation myopia. In the
      present study we examined the dependence of retinal dopamine release in chicks on
      illuminance during light-dark cycles and in continuous light, and the role of
      retinal dopamine release in illuminance dependent refractive development. Newly
      hatched chicks (n = 166) were divided into two experimental groups, a dopamine (n
      = 88) and a refraction group (n = 78). Both groups were further divided into six
      illumination groups for exposure of chicks to illuminances of 50, 500 or 10,000
      lux of incandescent illumination (referred to throughout as low, medium, and high
      illuminance, respectively), either under a light-dark cycle with lights on
      between 7 AM and 7 PM or under continuous illumination. For the dopamine
      experiment, chicks were euthanized and vitreous was extracted on day 14 post
      hatching at 7, 8 AM and 1 PM. Vitreal dihydroxyphenylacetic acid (DOPAC) and
      dopamine concentrations were quantified by high-performance liquid chromatography
      coupled to electrochemical detection. For the refraction experiment, chicks
      underwent refraction, keratometry and A-scan ultrasonography on days 30, 60 and
      90 post-hatching, and each of those measurements was correlated with vitreal
      DOPAC concentration measured at 1 PM (representing the index of retinal dopamine
      release). The results showed that under light-dark cycles, vitreal DOPAC
      concentration was strongly correlated with log illuminance, and was significantly
      correlated with the developing refraction, corneal radius of curvature, and axial
      length values. On day 90, low vitreal DOPAC concentrations were associated with
      myopia (-2.41 +/- 1.23 D), flat cornea, deep anterior and vitreous chambers, and
      thin lens. Under continuous light, vitreal DOPAC concentrations measured at 1 PM
      in the low, medium, and high illuminance groups did not differ from the
      concentrations measured at 8 AM. On day 90, low DOPAC concentrations were
      associated with emmetropia (+0.63 +/- 3.61), steep cornea, and shallow vitreous
      chamber. We concluded that ambient light over a log illuminance range of 1.69-4
      is linearly related to vitreal DOPAC concentration. Under both light-dark cycles
      and continuous light, the intensity of ambient light regulates the release of
      retinal dopamine. Refractive development is associated with illuminance dependent
      dopamine release.

PMID- 22960318
TI  - Tear fluid small molecular antioxidants profiling shows lowered glutathione in
      keratoconus.
AB  - Keratoconus (KC) is a non-inflammatory disease of the cornea involving structural
      changes. Oxidative stress is reported to be parts of its pathology, yet the tear
      antioxidant status contributed by smaller molecule antioxidants can be indicative
      of the disease. Therefore this study is an attempt to present the status of small
      molecule antioxidants in KC condition as well as the influence of contact lens
      wear (CLW) in KC as evaluated in the tear specimen. Tear fluid was collected
      using schirmer strips from KC with and without CLW (n = 40) with age matched
      controls (n = 29). Tear fluid antioxidants cysteine, ascorbic acid, glutathione,
      uric acid and tyrosine were determined by HPLC electrochemical detection. Tear
      reactive oxygen species was estimated by fluorescence detection using
      dichlorodihydrofluorescein diacetate (DCF-DA) method. The corneal epithelial mRNA
      expression of the enzymes, gamma-glutamine cysteinyl synthase (gamma-GCS) and
      gamma-glutamyl transpeptidase (gamma-GT) by semiquantitative RT-PCR. Among the
      five antioxidant molecules estimated, GSH decreased significantly 50.9 +/- 9.4
      MUM in control and 16 +/- 5.7 MUM in KC (p = 0.015) with increase in tyrosine
      13.9 +/- 2.6 MUM in control, 30 +/- 6.4 MUM in KC cases (p = 0.022) and uric acid
      162 +/- 18 MUM in control and 210 +/- 32 MUM (p < 0.00) in KC compared to the
      controls. The ROS levels were increased significantly, 55.7 +/- 16.7 AU in KC and
      23.2 +/- 5.8 AU in controls (p = 0.023). No significant change in the tear
      antioxidants studied was observed in KC cases with and without CL wear. However
      tyrosine levels were increased significantly in CL wear amongst healthy controls
      compared to controls (p < 0.000). gamma-GCS and gamma-GT showed no significant
      change in KC epithelial cells. Though variations were seen in other antioxidants
      analysed, they had no statistical significance. Tear specimen in KC can indicate
      the antioxidant status. KC is associated with increased tear levels of tyrosine,
      uric acid and decrease in GSH apart from increased ROS. Glutathione decreases
      with increase in oxidative stress and this emphasises the need for antioxidants
      to balance the redox status in disease management of KC.

PMID- 22960320
TI  - Electrospun zein/eudragit nanofibers based dual drug delivery system for the
      simultaneous delivery of aceclofenac and pantoprazole.
AB  - Electrospun composite zein/eudragit nanofibers were developed with an aim to
      deliver two different classes of drugs simultaneously that would
      restrict/compensate the adverse effects of non-steroidal anti-inflammatory drugs
      (NSAIDs). Co-administration of proton pump inhibitors is beneficial for patients
      consuming NSAIDs for treating chronic ailments like arthritis. In this study,
      aceclofenac/pantoprazole loaded zein/eudragit S 100 nanofibers were developed
      using a single nozzle electrospinning process. The morphological analysis
      revealed the uniform and smooth surface of the drug loaded nanofibers. The
      physico-thermal characterization of nanofibers depicted the molecular integration
      of the drugs with the polymers and also confirmed that the drugs were evenly
      distributed in the nanofibers in an amorphous state. In vitro release studies
      ensure the efficiency of the developed fibers in sustaining the release of both
      the drugs up to 8h. In vivo animal experiments further confirmed that the co
      administration of pantoprazole along with aceclofenac reduced the gastro
      intestinal toxicity induced by NSAIDs. The histological evaluation revealed the
      preserved mucosal architecture of rat gastric tissue treated with drug loaded
      composite nanofibers. Thus, dual drug delivery system comprising polymers with
      different release characteristics has been successfully developed and further,
      oral delivery of aceclofenac with reduced side effects was achieved.

PMID- 22960319
TI  - Flux of ionic dyes across microneedle-treated skin: effect of molecular
      characteristics.
AB  - Drug flux across microneedle (MN)-treated skin is influenced by the
      characteristics of the MN array, formed microconduits and physicochemical
      properties of the drug molecules in addition to the overall diffusional
      resistance of microconduits and viable tissue. Relative implication of these
      factors has not been fully explored. In the present study, the in vitro
      permeation of a series of six structurally related ionic xanthene dyes with
      different molecular weights (MW) and chemical substituents, across polymer MN
      pretreated porcine skin was investigated in relation of their molecular
      characteristics. Dyes equilibrium solubility, partition coefficient in both n
      octanol or porcine skin/aqueous system, and dissociation constants were
      determined. Results indicated that for rhodamine dyes, skin permeation of the
      zwitterionic form which predominates at physiological pH, was significantly
      reduced by an increase in MW, the skin thickness and by the presence of the
      chemically reactive isothiocyanate substituent. These factors were generally
      shown to override the aqueous solubility, an important determinant of drug
      diffusion in an aqueous milieu. The data obtained provided more insight into the
      mechanism of drug permeation across MN-treated skin, which is of importance to
      both the design of MN-based transdermal drug delivery systems and of relevance to
      skin permeation research.

PMID- 22960321
TI  - Preparation and characterization of fusion processed solid dispersions containing
      a viscous thermally labile polymeric carrier.
AB  - The primary aim of the present study was to investigate the ability of
      hydroxypropyl and methoxyl substituted cellulose ethers to stabilize
      supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak
      base, after an acid-to-neutral pH transition. A secondary aim of the study was to
      evaluate the effect of fusion processes on polymer stability and molecular
      weight. Polymer screening studies showed that stabilization of ITZ
      supersaturation was related to the molecular weight of the polymer and levels of
      hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is
      characterized as having a high melt viscosity, was selected for solid dispersion
      formulation studies. Hot-melt extrusion processing of E50LV based compositions
      resulted in high torque loads, low material throughput and polymer degradation.
      KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as
      a method to prepare the solid dispersions with reduced levels of polymer
      degradation. An experimental design revealed that polymer molecular weight was
      sensitive to shearing forces and high temperatures. However, optimal processing
      conditions resulted in significantly reduced E50LV degradation relative to HME
      processing. The technique was effectively utilized to prepare homogenous solid
      solutions of E50LV and ITZ, characterized as having a single glass transition
      temperature over a wide range of drug loadings. All prepared compositions
      provided for a high degree of ITZ supersaturation stabilization.

PMID- 22960322
TI  - Protein spheres prepared by drop jet freeze drying.
AB  - In spray freeze drying (SFD) solutions are frozen by spraying into a very cold
      environment and subsequently dried by sublimation. In contrast to conventional
      freeze drying, spray freeze drying has the possibility to produce flowable
      lyophilizates which offers a variety of new pharmaceutical applications. Here, a
      drop jet nozzle is proposed as liquid dispenser that is able to produce droplets
      with a very narrow size distribution compared to standard methods. The drop jet
      nozzle is mounted in a spray tower designed to prevent direct contact of the
      product with the freezing medium. Various formulations have been tested
      containing lysozyme as model protein and stabilizers such as bovine serum
      albumin, polyvinylpyrrolidone or dextran in various concentrations and mannitol.
      Excellent free flowing and nearly monodispersed, porous particles are produced
      where particle properties can be controlled by formulation and process
      conditions. The particle diameter varied between 231 +/- 3 MUm and 310 +/- 10 MUm
      depending on the formulation composition. The lysozyme activity was >94 +/- 5%
      for all formulations exhibiting a full preservation of enzyme activity. This new
      method is very promising for the production of nearly monodisperse particulate
      lyophilizates in various therapeutic applications.

PMID- 22960323
TI  - Suitability of polymer materials for production of pulmonary microparticles using
      a PGSS supercritical fluid technique: thermodynamic behaviour of fatty acids,
      PEGs and PEG-fatty acids.
AB  - The thermodynamic behaviour of selected polymeric components for preparation of
      controlled release microparticles using supercritical carbon dioxide (scCO(2))
      processing was investigated. The polymeric materials selected were egg lecithin
      (a model for the lung surfactant phospholipid), poly(ethyleneglycol) (PEG) of
      different molecular weights, fatty acids (C18, C16, and C14), and physical blends
      of PEGs and fatty acids. In addition a range of PEG-stearates was also assessed.
      Analysis of thermodynamic behaviour was performed by differential scanning
      calorimetry (DSC) and by assessment of their interaction with scCO(2) in a high
      pressure variable volume view cell. The key criterion was to demonstrate a strong
      interaction with scCO(2) and to show liquefaction of the polymeric material at
      acceptable processing temperatures and pressures. Positive results should then
      indicate the suitability of these materials for processing by the Particle from
      Gas Saturated Solutions (PGSS) technique using scCO(2) to create microparticles
      for pulmonary administration. It was found that the materials tested interacted
      with scCO(2) and showed a sufficient lowering of their melting temperature (T(m))
      to make them suitable for use in the PGSS microparticle production rig. Fatty
      acids of low T(m) were shown to act as a plasticising agent and to lower the T(m)
      of PEG further during interaction with scCO(2).

PMID- 22960324
TI  - Transposable elements domesticated and neofunctionalized by eukaryotic genomes.
AB  - Whole genome sequencing has provided a massive amount of information about the
      origin, diversity and genomic impact of repetitive DNA sequences (repDNA). Among
      the many classes of repDNA, prokaryotic transposable elements (TEs) replicate,
      move, amplify and accumulate in invaded genomes and thus represent the major
      force in restructuring host genes and genomes during evolution. Similar to
      retroviruses, autonomous TEs became part of the host genomes, and after their
      molecular domestication, they became functional genes (genomic fossils) in
      eukaryotic genomes. In this review, examples of the domestication events are
      discussed, some of which are known to be induced by biotic and abiotic stressors.

PMID- 22960325
TI  - A comparison of the effects of digoxin, ouabain and milrinone on naloxone
      precipitated withdrawal syndrome in mice.
AB  - Modulation of Na(+), K(+)-ATPase activity by acute and chronic opiates has been
      established for many years. However, the effects of digoxin, a putative inhibitor
      of Na(+), K(+)-ATPase, on naloxone-precipitated morphine withdrawal syndrome are
      unknown. In the present study, a digoxin dose-response curve was conducted to
      observe the effects on naloxone-precipitated withdrawal and locomotor activity in
      mice. Higher doses of digoxin (1.0 and 2.5 mg/kg) inhibited locomotor activity
      and naloxone-precipitated withdrawal jumping and weight loss, while lower doses
      of digoxin (0.1 and 0.25 mg/kg) inhibited withdrawal weight loss precipitated by
      naloxone without affecting locomotor activity and naloxone-precipitated
      withdrawal jumping. To explore the possible mechanisms underlying this behavior,
      another Na(+), K(+)-ATPase inhibitor ouabain, which does not cross the blood
      brain barrier, and another cardiotonic drug milrinone, a non-inhibitor of Na(+),
      K(+)-ATPase, were also included in the present study. Both milrinone and ouabain
      inhibited, in a dose-dependent manner, naloxone-precipitated weight loss while
      neither affected naloxone-precipitated withdrawal jumping nor locomotor activity
      in mice. These results indicate that both the cardiotonic effects and central
      inhibition of Na(+), K(+)-ATPase contribute to the inhibitory effects of digoxin
      on morphine withdrawal syndrome in mice.

PMID- 22960326
TI  - Reversion of P-glycoprotein-mediated multidrug resistance by guggulsterone in
      multidrug-resistant human cancer cell lines.
AB  - Multidrug resistance (MDR) presents a serious problem in cancer chemotherapy. Our
      previous studies have shown that guggulsterone could reverse MDR through
      inhibiting the function and expression of P-glycoprotein (P-gp). The present
      study is to further investigate the reversal effects of guggulsterone on MDR in
      drug-resistant cancer cell lines. The effects of guggulsterone on MDR1mRNA gene
      expression, intracellular pH, P-gp ATPase activity and glucosylceramide synthase
      (GCS) expression were assessed by RT-PCR, Laser Scanning Confocal Microscope
      using the pH-sensitive fluorescent probe BCECF-AM, Pgp-Glo assay system, and flow
      cytometric technology, respectively. The results showed that guggulsterone
      ranging from 2.5 to 80 MUM significantly promoted the activity of P-gp ATPase in
      a dose-dependent manner. The intracellular pH of K562/DOX cells was found to be
      higher than K562 cells. After treatment with guggulsterone (1, 3, 10, 30, 100
      MUM), intracellular pH of K562/DOX cells decreased in a dose- and time-dependent
      manner. However, the present study revealed that guggulsterone ranging from 3 to
      100 MUM had little influence on MDR1 gene expression in K562/DOX cells. Further,
      the isogenic doxorubicin-resistant MCF-7/DOX cells exhibited a 4.9-fold increase
      in GCS level as compared with parental MCF-7 human breast cancer cells. After
      treatment with guggulsterone (0.1, 1, 10 MUM) for 48 h, MCF-7/DOX cells were
      found to have no change of GCS protein expression amount. Guggulsterone might be
      a potent MDR reversal agent, and its mechanism on MDR needs more research.

PMID- 22960327
TI  - Metal-ion directed synthesis of N2O2 type chelate complexes of Ni(II), Cu(II) and
      Zn(II): spectral, thermal and single crystal studies.
AB  - A set of Ni(II), Cu(II) and Zn(II) complexes of Schiff base have been synthesized
      by one pot condensation reaction of 2-hydroxy-4-methoxybenzophenone with 1,3
      diaminopropane in 1:2:1 molar ratio. They have been characterized by elemental
      analysis, conductance measurement, thermal analysis (TGA/DTA), FT-IR, (1)H-NMR,
      EPR spectra, ESI-MS and electronic spectral studies. In order to establish the
      geometry, a single crystal X-ray structure for [Ni(L)] complex was determined. It
      crystallizes in monoclinic system having unit cell parameters a=14.015(5)A,
      b=13.391(5)A, c=14.931(5)A and alpha=90.000(5)(o), beta=112.237(5)(o),
      gamma=90.000(5)(o) with P 2(1)/c space group. No pi-pi stacking interaction was
      obtained in molecular packing diagram. A square-planar geometry has been
      confirmed for Ni(II) complex. Furthermore, on the basis of elemental analysis,
      IR, UV-visible and EPR data a square-planar geometry for Cu(II) and a distorted
      octahedral geometry for the Zn(II) complex has been established. In case of
      Zn(II) complex NO(3)(-) group was found to be coordinated in monodentate fashion.
      The low molar conductivity values of the complexes measured in chloroform and
      DMSO suggest their non-ionic nature.

PMID- 22960328
TI  - Common Mediterranean fever (MEFV) gene mutations associated with ankylosing
      spondylitis in Turkish population.
AB  - Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease.
      Mediterranean fever (MEFV) gene, which has already been identified as being
      responsible for familial Mediterranean fever (FMF), is also a suspicious gene for
      AS because of the clinical association of these two diseases. The aim of this
      study was to explore the frequency and clinical significance of MEFV gene
      mutations (M694V, M680I, V726A, E148Q and P369S) in a cohort of Turkish patients
      with AS. Genomic DNAs of 103 AS patients and 120 controls were isolated and
      genotyped using polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) methods. There was a statistically significant difference of
      the MEFV gene mutation carrier rates between AS patients and healthy controls
      (p=0.004, OR: 2.5, 95% CI: 1.32-4.76). This association was also observed in
      allele frequencies (p=0.005, OR: 2.3, 95% CI: 1.27-4.2). A relatively higher
      frequency was observed for M694V mutation in AS patients than controls (10.7%
      versus 4.2% , p=0.060). There were no significant differences between MEFV
      mutation carriers and non-carriers with respect to the clinical and demographic
      characteristics. The results of this study suggest that MEFV gene mutations are
      positively associated with a predisposition to develop AS.

PMID- 22960329
TI  - Plasma C-reactive protein is not related to sinus non-conversion by maze
      procedure adjunct to mitral valve surgery.
AB  - In Framingham cohort study, C-reactive protein was not associated with incident
      atrial fibrillation (AF) after adjustment for left atrial size. This study
      examined whether levels of plasma inflammatory markers would be significant risk
      factors for failed maze procedure for AF. This study enrolled 88 patients with
      mitral valve disease undergoing valve surgery (n=32, sinus control group) or
      concomitant maze procedure for persistent atrial fibrillation (AF) (n=56, AF
      group). The mean follow-up in the AF group was 55.0 +/- 17.5 months. The AF and
      sinus control groups did not differ in preoperative levels of C-reactive protein
      (p=0.636). In the AF group receiving maze procedure, the sinus conversion (n=37)
      and non-conversion (n=19) groups did not significantly differ in preoperative
      levels of interleukin-6 (p=0.607) and tumor necrosis factor-alpha (p=0.379). In
      multivariate analysis after adjustment for preoperative plasma inflammatory
      markers, independent factors associated with sinus conversion were AF duration
      (p=0.003), and left atrial area (p=0.014). In conclusion, plasma inflammatory
      markers are not associated with sinus non-conversion by radiofrequency maze
      procedure.

PMID- 22960330
TI  - Micro-RNA expression in the urinary sediment of patients with chronic kidney
      diseases.
AB  - BACKGROUND: Evidence indicates that microRNAs (miRNA) play a role in the
      pathogenesis of chronic kidney diseases (CKD). We explored the possibility of
      using urinary miRNA as non-invasive biomarkers for CKD. METHODS: We quantified
      miRNA expression in urinary sediment of 56 CKD patients who underwent kidney
      biopsy. Patients were followed for 16.2 +/- 15.5 months. RESULTS: Patients with
      diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with
      IgA nephropathy had higher urinary miR-17 expression, than other diagnosis
      groups. Baseline proteinuria had significant inverse correlation with urinary
      expression of miR-15, miR-192, and miR-216a; baseline renal function correlated
      with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of
      renal function decline correlated with urinary expression of miR-21 (r=0.301,
      p=0.026) and miR-216a (r=0.515, p < 0.0001). Patients with a high urinary
      expression of miR-21 and miR-216a had better dialysis-free survival than those
      with low expression (log rank test, p=0.005 and p=0.003, respectively).
      CONCLUSIONS: Urinary miR-21 and miR-216a expression correlated with the rate of
      renal function decline and risk of progression to dialysis-dependent renal
      failure. Our results suggest that urinary miRNA profiling has the potential of
      further development as biomarkers of CKD.

PMID- 22960331
TI  - DJ-1 variants in Indian Parkinson's disease patients.
AB  - Parkinson's disease (PD) is a common neurodegenerative movement disorder. Among
      the candidate genes, DJ-1 accounts for about 1% of the cases in different
      populations. We aim to find the contribution of the gene towards PD among
      Indians. By screening DJ-1 in 308 PD patients of eastern India and 248 ethnically
      matched controls, a total of 21 nucleotide variants - including two nonsynonymous
      changes - were detected. p.Arg98Gln was identified in 6 unrelated patients and 2
      controls while p.Val35Ile, a novel change, was found only in 2 unrelated
      patients. A SNP (rs7517357) was observed to be moderately associated with
      increased risk of PD (p< 0.05). The deletion allele (g.168_185del) of a known 18
      bp del/ins/dup polymorphism was found to be over represented (p< 0.05) among
      older patients (> 40 years) compared to the controls (> 45 years). Two of the
      patients, also heterozygotes for PINK1 mutation, had more severe disease
      phenotypes, consistent with the reported interaction between PINK1 and DJ-1 gene
      products [19]. Our results demonstrate that up to 3.9% (12/308) of PD patients of
      eastern India harbor DJ-1 variants that should be explored further for any causal
      relationship with PD.

PMID- 22960332
TI  - Genetic association and gene-gene interaction of HAS2, HABP1 and HYAL3 implicate
      hyaluronan metabolic genes in glaucomatous neurodegeneration.
AB  - Hyaluronan (HA) plays a significant role in maintaining aqueous humor outflow in
      trabecular meshwork, the primary ocular tissue involved in glaucoma. We examined
      potential association of the single nucleotide polymorphisms (SNPs) of the HA
      synthesizing gene - hyaluronan synthase 2 (HAS2), hyaluronan binding protein 1
      (HABP1) and HA catabolic gene hyaluronidase 3 (HYAL3) in the primary open angle
      glaucoma (POAG) patients in the Indian population. Thirteen tagged SNPs (6 for
      HAS2, 3 for HABP1 and 4 for HYAL3) were genotyped in 116 high tension (HTG), 321
      non-high tension glaucoma (NHTG) samples and 96 unrelated, age-matched, glaucoma
      negative, control samples. Allelic and genotypic association were analyzed by
      PLINK v1.04; haplotypes were identified using PHASE v2.1 and gene-gene
      interaction was analyzed using multifactor dimensionality reduction (MDR) v2.0.
      An allelic association (rs6651224; p= 0.03; OR: 0.49; 95% CI: 0.25-0.94) was
      observed at the second intron (C>G) of HAS2 both for NHTG and HTG. rs1057308
      revealed a genotypic association (p=0.03) at the 5' UTR of HAS2 with only HTG.
      TCT haplotype (rs1805429 - rs2472614 - rs8072363) in HABP1 and TTAG and TTGA
      (rs2285044 - rs3774753 - rs1310073 - rs1076872) in HYAL3 were found to be
      significantly high (p< 0.05) both for HTG and NHTG compared to controls. Gene
      gene interaction revealed HABP1 predominantly interacts with HAS2 in HTG while it
      associates with both HYAL3 and HAS2 in NHTG. This is the first genetic evidence,
      albeit from a smaller study, that the natural polymorphisms in the genes involved
      in hyaluronan metabolism are potentially involved in glaucomatous
      neurodegeneration.

PMID- 22960333
TI  - Polymorphisms of glutathione S-transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi
      1 (GSTP1) genes and epithelial ovarian cancer risk.
AB  - BACKGROUND: Exposure of ovarian cells to estrogen, which is detoxified by
      glutathione S-transferases (GSTs), has been associated with epithelial ovarian
      cancer (EOC) development. OBJECTIVES: We tested in this study whether the GSTM1,
      GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. MATERIALS AND
      METHODS: Genomic DNA from 132 EOC patients and 132 controls was analyzed by
      polymerase chain reaction and restriction fragment length polymorphism methods.
      The differences between groups were analyzed by chi<formula> ^{2}</formula> or
      Fisher's exact test. RESULTS: The frequencies of GSTP1 Ile/Ile (57.6% versus
      45.5%, P=0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P=0.03) and
      GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P=0.007)
      genotypes were higher in patients than in controls. Individuals with the
      respective genotypes had a 1.80 (95% CI: 1.06-3.06), 2.38 (95% CI: 1.08-5.24) and
      11.28 (95%CI: 1.95-65.30)-fold increased risks of EOC than those with the
      remaining genotypes. CONCLUSIONS: Our data present preliminary evidence that
      GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute
      important inherited EOC determinants in individuals from Southeastern Brazil.

PMID- 22960334
TI  - Subphenotype-dependent disease markers for diagnosis and personalized treatment
      of autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are a collection of neurodevelopmental disorders
      that are currently diagnosed solely on the basis of abnormal reciprocal language
      and social development as well as stereotyped behaviors. Without genetic or
      molecular markers for screening, individuals with ASD are typically not diagnosed
      before the age of 2, with milder cases diagnosed much later. Because early
      diagnosis is tantamount to early behavioral intervention which has been shown to
      improve individual outcomes, an objective biomarker test that can diagnose at
      risk children perinatally is a medical imperative. The rapidly increasing
      prevalence of ASD in the United States (now estimated at 1 in 88 individuals)
      also makes early diagnosis and intervention a public health imperative. This
      article reviews recent genome-wide (genomic) approaches to the identification of
      disease markers that may be used not only for diagnosis of ASD, but also for the
      informed development of novel drugs that target specific core symptoms of ASD.
      Because of the heterogeneity of clinical manifestations associated with the ASD
      population, this review also addresses the importance of dividing individuals
      with ASD into clinically relevant subphenotypes in the quest to identify
      appropriate biomarkers.

PMID- 22960335
TI  - A songbird animal model for dissecting the genetic bases of autism spectrum
      disorder.
AB  - The neural and genetic bases of human language development and associated
      neurodevelopmental disorders, including autism spectrum disorder (ASD), in which
      language impairment represents a core deficit, are poorly understood. Given that
      no single animal model can fully capture the behavioral and genetic complexity of
      ASD, work in songbird, an experimentally tractable animal model of vocal
      learning, can complement the valuable tool of rodent genetic models and
      contribute important insights to our understanding of the communication deficits
      observed in ASD. Like humans, but unlike traditional laboratory animals such as
      rodents or non-human primates, songbirds exhibit the capacity of vocal learning,
      a key subcomponent of language. Human speech and birdsong reveal important
      parallels, highlighting similar developmental critical periods, a homologous
      cortico-basal ganglia-thalamic circuitry, and a critical role for social
      influences in the learning of vocalizations. Here I highlight recent advances in
      using the songbird model to probe the cellular and molecular mechanisms
      underlying the formation and function of neural circuitry for birdsong and, by
      analogy, human language, with the ultimate goal of identifying any shared or
      human unique biological pathways underscoring language development and its
      disruption in ASD.

PMID- 22960336
TI  - Mutant mouse models of autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental
      diseases characterized by a triad of specific behavioral traits: abnormal social
      interactions, communication deficits and stereotyped or repetitive behaviors.
      Several recent studies showed that ASDs have a strong genetic basis, contributing
      to the discovery of a number of ASD-associated genes. Due to the genetic
      complexity of these disorders, mouse strains with targeted deletion of ASD genes
      have become an essential tool to investigate the molecular and neurodevelopmental
      mechanisms underlying ASD. Here we will review the most relevant genetic mouse
      models developed by targeted inactivation of ASD-associated genes, and discuss
      their importance for the development of novel pharmacological therapies of these
      disorders.

PMID- 22960337
TI  - The role of the FOXP family of transcription factors in ASD.
AB  - Autism spectrum disorders (ASD) is a neurodevelopmental disease with complex
      genetics; however, the genes that are responsible for this disease still remain
      mostly unknown. Here, we focus on the FOXP family of transcription factors as
      there is emerging evidence strongly linking these genes to ASD and other genes
      implicated in ASD. The FOXP family of genes includes three genes expressed in the
      central nervous system: FOXP1, FOPX2, and FOXP4. This unique group of
      transcription factors has known functions in brain development as well as the
      evolution of language. We will also discuss the other genes including
      transcriptional targets of FOXP genes that have been found to be associated with
      language and may be important in the pathophysiology of ASD. Finally, we will
      review the emerging animal models currently being used to study the function of
      the FOXP genes within the context of ASD symptomology. The combination of gene
      expression and animal behavior is critical for elucidating how genes such as the
      FOXP family members are key players within the framework of the developing brain.

PMID- 22960338
TI  - KPNA3 variation is associated with schizophrenia, major depression, opiate
      dependence and alcohol dependence.
AB  - KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this
      study we investigated the possible association between KPNA3 variation and
      schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders
      we also analysed major depression, PTSD, nicotine dependent, alcohol dependent
      and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach
      we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157
      schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate
      dependent patients, 231 alcohol dependent patients, 147 nicotine dependent
      patients and 266 major depression patients. One SNP rs2273816 was found to be
      significantly associated with schizophrenia, opiate dependence and alcohol
      dependence at the genotype and allele level. Major depression was also associated
      with rs2273816 but only at the allele level. Our study suggests that KPNA3 may
      contribute to the genetic susceptibility to schizophrenia as well as other
      psychiatric disorders.

PMID- 22960339
TI  - Antioxidant effects of potassium ascorbate with ribose therapy in a case with
      Prader Willi Syndrome.
AB  - Oxidative stress (OS) is involved in several human diseases, including obesity,
      diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We
      previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann
      Syndrome (BWS). Here we describe the clinical case of a female patient with
      Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by
      obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a
      continuous and important production of free radicals takes place. We verified the
      presence of OS by measuring a redox biomarkers profile including total
      hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced
      oxidation protein products (AOPP) and isoprostanes (IPs). Thus we introduced in
      therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in
      addition to GH therapy and we monitored the redox biomarkers profile for four
      years. A progressive decrease in OS biomarkers occurred until their
      normalization. In the meantime a weight loss was observed together with a steady
      growth in standards for age and sex.

PMID- 22960341
TI  - The value of combined use of survivin mRNA and matrix metalloproteinase 2 and 9
      for bladder cancer detection in voided urine.
AB  - OBJECTIVE: In a trial to improve the diagnostic efficacy of conventional urine
      cytology we determine survivin RNA and matrix metalloproteinase 2 and 9 in urine
      of bladder cancer cases. METHOD: Voided urine specimens were collected from
      patients with histologically confirmed bladder urothelial carcinoma (Group 1;
      n=46), urological patients without urothelial carcinoma (Group 2; n=20), and
      healthy volunteers (Group 3; n=20). Urine cytology, survivin RNA was estimated by
      qualitative nested RT-PCR and MMP-2, MMP-9 activity were detected by gelatin
      zymography. The expression of survivin RNA and matrix metalloproteinase 2 and 9
      in bladder cancer was compared with benign and normal cases. RESULTS: Positivity
      rates of survivin RNA and MMPs zymography were significantly different among the
      3 groups. Urine survivin detection by qualitative nested RT-PCR showed 76.1%
      sensitivity and 95% specificity. The overall sensitivity, specificity of urinary
      MMP zymography was 67.3%, 90% respectively. The combined use of urine cytology
      with urine survivin or MMPs zymography increased sensitivity of urine cytology
      from 50% to 84.7%. The highest sensitivity (95.6%) was obtained on combining the
      three markers. CONCLUSION: Survivin RNA and MMPS zymography can be considered as
      promising noninvasive markers for bladder cancer early detection. Combined use of
      the three markers improved the sensitivity for detecting bladder cancer.

PMID- 22960342
TI  - Urinary chiro- and myo-inositol levels as a biological marker for type 2 diabetes
      mellitus.
AB  - BACKGROUND: The aim of this study was to investigate the role of the urinary
      chiro- and myo-inositol levels in predicting type 2 diabetes mellitus (T2DM).
      SUBJECTS AND METHODS: A total of 212 normal controls and 101 type 2 diabetic
      patients were enrolled this study. The concentrations of urinary chiro- and myo
      inositol were measured by high performance liquid chromatography/mass
      spectrometry. RESULTS: The concentration of urinary chiro-inositol was
      significantly higher in the diabetic subjects (2.24 +/- 5.18 ng/L) than those in
      the control group (0.38 +/- 0.62 ng/L; p < 0.001). The urinary myo-inositol level
      of the diabetic subjects (36.95 +/- 37.77 ng/L) was also significantly higher
      than that of the controls (8.17 +/- 13.29 ng/L; p < 0.001). The urinary chiro
      inositol multiplied by myo-inositol level of the diabetic subjects (148.10 +/-
      544.91) was significantly higher than in the controls (5.12 +/- 24.15; p <
      0.001). The area under the receiver operating characteristic curve for the
      urinary chiro-inositol multiplied by myo-inositol level to predict T2DM was 0.840
      (confidence interval 0.789-0.891, p < 0.001). The cut-off value for the urinary
      chiro-inositol multiplied by myo-inositol level to predict T2DM was 2.20
      (sensitivity 81.3%, specificity 70.3%). CONCLUSIONS: The urinary chiro- and myo
      inositol concentrations were increased in the type 2 diabetic patients and the
      urinary chiro- times the myo-inositol was considered to be a sufficient marker in
      predicting T2DM.

PMID- 22960343
TI  - Autism: from genetics to biomarkers.

PMID- 22960344
TI  - Circulating levels of high molecular weight (HMW) adiponectin and total
      adiponectin in relation to fat distribution, oxidative stress and inflammation in
      Asian Indians.
AB  - AIM: To look at the association of total and high molecular weight (HMW)
      adiponectin with markers of fat distribution, oxidative stress and inflammation
      in Asian Indians. METHODS: A total of 120 subjects were chosen randomly from
      Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF
      alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive
      protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid
      peroxidation was measured by Tbars assay and protein carbonyl content was
      assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by
      computed tomography (CT) scan. RESULTS: When stratified based on the tertiles of
      visceral fat, the levels of total (p=0.03) and HMW adiponectin (p=0.007) were
      highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of
      subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the
      levels of total (p=0.03) and HMW adiponectin decreased (p=0.002). The levels of
      HMW (p< 0.001) but not total adiponectin was also found to decrease with
      increasing tertiles of Protein carbonyl content. The levels of Total (p=0.02) and
      HMW adiponectin (p=0.004) were highest in the first tertile of oxidized LDL
      followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total
      (p=0.01) and HMW adiponectin (p=0.004) was found to decrease. With increasing
      tertiles of hs-CRP, Total (p=0.005) and HMW adiponectin (p=0.007)was found to
      decrease. CONCLUSION: Oxidative stress markers, visceral but not subcutaneous fat
      and inflammation are associated with total and HMW adiponectin levles in Asian
      Indians.

PMID- 22960345
TI  - Associations of killer cell immunoglobulin- like receptor genes with rheumatoid
      arthritis.
AB  - OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory
      disease of unknown etiology. Killer cell immunoglobulin-like receptors are
      expressed on the surface of natural killer cells and CD28null T-cells, both
      present in synovial membrane of RA. Therefore we evaluated the associations of
      KIR genes with RA. METHODS: 16 KIR genes were genotyped in 100 healthy subjects
      (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences in KIR
      genotypes and gene frequencies were assessed using the <formula>X^{2}</formula>
      test. RESULTS: Gene frequency of KIR2DL3 was lower in RA than in HS (p= 0.0019),
      whereas KIR2DL2 and KIR2DS2 were higher in RA than HS (p =0.0004 and p = 0.0487,
      respectively). In addition were identified 38 genotypes (from G1-G38) in both
      studied groups, and the genotype frequencies of G1, G6 and G14 showed significant
      differences (p =0.0001, p =0.0208 and p =0.0300, respectively). CONCLUSIONS: The
      presence of KIR2DL2, KIR2DS2 and absence of KIR2DL3 are associated with RA.
      Moreover, two genotypes BX are associated with RA. These results suggest that
      KIRs can be involved in RA susceptibility.

PMID- 22960346
TI  - Association of progranulin and high sensitivity CRP concentrations in gingival
      crevicular fluid and serum in chronic periodontitis subjects with and without
      obesity.
AB  - BACKGROUND: Obesity is considered as a strong risk factor of inflammatory
      periodontal tissue destruction. The purpose of this study is to determine
      presence of progranulin (PGRN) and high sensitivity C reactive protein (hs CRP)
      levels in serum and gingival crevicular fluid (GCF) in obese subjects with
      chronic periodontitis and to find an association, if any. MATERIAL AND METHODS:
      40 subjects (20 males and 20 females) were selected based on their clinical
      parameters into four groups (10 subjects in each group): group 1 (healthy non
      obese), group 2 (healthy obese), group 3 (non obese with chronic periodontitis)
      and group 4 (obese with chronic periodontitis). Serum and GCF PGRN levels were
      estimated by enzyme linked immunosorbant assay (ELISA) and hs CRP levels were
      estimated by immunoturbidimetry method. RESULTS: The mean PGRN and hs CRP
      concentration both in serum and GCF were highest for group 4 followed by group 3,
      group 2 and least in Group 1. CONCLUSION: PGRN and hs CRP may be novel biomarkers
      of the chronic inflammatory response in obesity and chronic periodontitis.

PMID- 22960347
TI  - Acanthamoeba interactions with the blood-brain barrier under dynamic fluid flow.
AB  - Acanthamoeba granulomatous encephalitis (AGE), caused by Acanthamoeba
      castellanii, is a fatal infection of immunocompromised individuals. The
      pathogenesis of blood-brain barrier (BBB) breach remains unknown. Using a novel
      in vitro BBB infection model under flow conditions, demonstrates that increases
      in flow rates lead to decreased binding of A. castellanii to host cells. This is
      a distinct departure from previous findings under static conditions. However,
      similarly to static conditions binding of A. castellanii to host cells is host
      mannose dependent. Disruption of the host cell monolayer was independent of
      amoeba binding, but dependent on secreted serine proteases. For the first time we
      report the binding dynamics of A. castellanii under physiological conditions,
      showing that BBB disruption is not directly linked to binding, instead it is
      reliant on secreted proteases. Our results offer a platform on which therapies
      designed at modulating physiological parameters can improve the outcome of
      infection with A. castellanii.

PMID- 22960348
TI  - Quinone reductase (QR) inducers from Andrographis paniculata and identification
      of molecular target of andrographolide.
AB  - In the present study, it was demonstrated that the petroleum extract of
      Andrographis paniculata (AP) had quinone reductase (QR) inducing activity, which
      might be attributed to the modification of key cysteine residues in Keap1 by
      Michael addition acceptors (MAAs) in it. To screen MAAs in AP, glutathione (GSH)
      was employed, and a LC/MS/MS method was implied. Three compounds,
      andrographoside, andrographolide, 14-deoxy-14,15-dehydroandrographolide were
      revealed could well conjugated with GSH. Then, andrographolide along with 4 new
      and 14 known compounds were isolated to conduct QR induction evaluation, and the
      CD (the concentration required to double the activity of QR) value of
      andrographolide is 1.43MUM. The QR induce activity of andrographolide might be
      attributed to its targeting multiple cysteine residues in Keap1, therefore, the
      alkylation of Keap1 by andrographolide was further studied and the result showed
      that four cysteine residues: Cys77, Cys151, Cys273 and Cys368 were alkylated,
      which indicated that Keap1 is a potential target for the QR induce activity of
      andrographolide.

PMID- 22960349
TI  - Phillyrin produced by Colletotrichum gloeosporioides, an endophytic fungus
      isolated from Forsythia suspensa.
AB  - To investigate the phillyrin-producing endophytic fungi from the medicinal plant
      Forsythia suspensa, a total of 24 strains of endophytic fungi were isolated from
      the healthy stems, leaves and fruits of the plant, 9 from stems, 5 from leaves,
      and 10 from fruits respectively. All fungal isolates were fermented in liquid PDA
      medium and their extracts were preliminary analyzed by TLC. One isolated strain
      G10, which was from the fruit of F. suspensa, had the same R(f) value as
      authentic phillyrin. The potential phillyrin-producing fungus G10 was further
      analyzed by HPLC and HPLC-MS, and the results showed that the isolate G10
      possessed of a retention time and ion peaks identical with the authentic compound
      phillyrin. The isolate G10 was identified as Colletotrichum gloeosporioides based
      on the morphological characteristics and ITS sequence analysis. The current
      research indicates that the numerous endophytic fungi inside the medicinal plants
      are precious resource for the pharmaceutical natural products that are originally
      from the plants.

PMID- 22960350
TI  - Physicians' and nurses' experiences of end-of-life decision-making in geriatric
      settings.
AB  - BACKGROUND AND AIMS: In Italy there is a paucity of empirical data on practices
      concerning end-of-life decisions (ELDs) in geriatrics. We aimed to investigate
      the frequency and characteristics of ELDs made by Italian physicians and nurses
      in the geriatric setting. METHODS: In 2009, an anonymous questionnaire was sent
      to 54 geriatric units, 21 hospices, and 382 nursing homes in the Veneto and
      Trentino Alto Adige regions, and to professionals in the area who are members of
      the Italian Gerontology and Geriatrics Association. RESULTS: This paper reports
      the results of 552 questionnaires answered by 171 physicians, 368 nurses and 13
      professionals who did not state their profession. Death was preceded by decisions
      to start or continue treatments likely to prolong the patients' life in 51.3% of
      cases. The proportion of deaths preceded by a decision to end life (DEL) was
      20.8%; 18% of DELs concerned non-treatment decisions. There were 9 cases of
      ending of life without patient's explicit request. No cases of doctor-assisted
      suicide were reported, while there were 2 cases of euthanasia, one reported by a
      physician and one by a nurse. CONCLUSION: In geriatrics, DELs often precede the
      deaths of terminally-ill Italian patients. Nurses report making DELs more often
      than physicians, especially in incompetent patients. Continuous deep sedation was
      adopted by 39.5% of the Italian physicians for deaths not occurring suddenly and
      unexpectedly. Our report on physicians' and nurses' experiences of ELD making in
      geriatric settings can offer a valuable contribution to the current debate on end
      of-life treatment, an issue that goes beyond national borders.

PMID- 22960351
TI  - Bodies of knowledge: nature, holism and women's plural health practices.
AB  - The proliferation of complementary and alternative medicine (CAM), and women's
      high level of engagement with these practices, has presented sociology with a
      range of questions regarding gender, embodiment and identity work in the context
      of contemporary medical pluralism. The current study, drawing on 60 qualitative
      interviews with women from the Australian Longitudinal Study on Women's Health
      (ALSWH), examines how a group of Australian women negotiate CAM and biomedicine
      in a range of health and illness contexts. Selected from the mid-aged cohort of
      this national study, here we explore their accounts of engagement with CAM and
      biomedicine, unpacking their logics underpinning, and rhetorical practices
      surrounding, their therapeutic engagement. The results provide significant
      insight into: the importance of ideas about nature, holism and strengthening;
      perceptions of the harshness and softness of medicines for women's bodies; and,
      the relative importance of scientific proof vis-a-vis individual subjectivities.
      Ultimately, their accounts illustrate gendered and embodied strategies of
      strategic integration, and importantly, border crossing. We conclude that while
      women's engagement with CAM and biomedicine may be indeed be gendered in
      character, we suggest a rethinking of gender-based resistance (to biomedicine) or
      gender-alignment (to CAM) arguments; the notion of women as designers would more
      adequately capture the landscapes of contemporary medical pluralism.

PMID- 22960352
TI  - Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients
      with recurrent, platinum-resistant primary epithelial ovarian or primary
      peritoneal carcinoma.
AB  - OBJECTIVE: We examined the safety and efficacy of combining bevacizumab with
      albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum
      resistant primary epithelial ovarian or peritoneal carcinoma. METHODS: Patients
      had measurable disease per RECIST guidelines, progressing within 6 months after a
      prior course of platinum-based treatment. Patients received ab-paclitaxel
      100mg/m(2) given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28
      day cycle with bevacizumab 10mg/kg given on days 1 and 15. RESULTS: Forty-eight
      patients with an average 1.8 prior lines of treatment participated. The overall
      response rate was 50% (24/48) (95% CI, 34.8% - 65.1%), with 4 complete and 20
      partial responses. Fourteen patients (29%) had stable disease, whereas eight
      (17%) had progressive disease, and two (4%) were not evaluable. Patients received
      a median of 6 treatment cycles (range, 1 - 31 cycles). The median progression
      free survival was 8.08 months (95% CI, 5.78 - 10.15 months); 6 month progression
      free rate was 62.5% (95% CI, 47.8%-77.2%); median overall survival was 17.15
      months (95% CI, 13.57 - 23.82 months). Grade 3-4 adverse events included
      gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%).
      CONCLUSIONS: Ab-paclitaxel with bevacizumab clearly demonstrates antitumor
      activity and manageable toxicity profile in patients with recurrent, platinum
      resistant ovarian carcinoma. This regimen should be evaluated in a larger
      randomized trial.

PMID- 22960353
TI  - Synthesis, characterization and modification of functionalized pyrimidine
      stabilized gold nanoparticles on ITO electrode for the determination of tannic
      acid.
AB  - This paper describes the synthesis of 4-amino-6-hydroxy-2-mercaptopyrimidine
      capped gold nanoparticles (AHMP-AuNPs) in aqueous medium and their immobilization
      on indium tin oxide (ITO) electrode modified with (3
      mercaptopropyl)trimethoxysilane (MPTS) sol-gel for the determination of tannic
      acid (TA). The high resolution transmission electron microscopy (HR-TEM) images
      show that the particles are spherical in shape with a diameter of ~6 nm. The
      heterogeneous electron transfer rate constant (k(et)) of [Fe(CN)6]3-/4- at
      ITO/MPTS/AHMP-AuNPs electrode was found to be 1.14*10-7 m/s. This value was much
      higher than the values obtained at ITO/MPTS (4.94*10-9 m/s) and bare ITO (8.79*10
      8 m/s) electrodes, indicating that the electron transfer reaction was faster at
      AuNPs modified electrode. Further, the ITO/MPTS/AHMP-AuNPs electrode shows
      excellent electrocatalytic activity toward TA oxidation when compared to bare ITO
      electrode. This was understood from the obtained higher heterogeneous rate
      constant (k(s)) value at AuNPs modified electrode (7.35*10-5 m/s) than at bare
      ITO electrode (5.45*10-6 m/s). Using the amperometry method, detection of 20
      nmol/L TA was achieved. The practical application of the present method was
      demonstrated by determining the concentration of TA in commercial beer samples.

PMID- 22960354
TI  - Formation and function of phosphatidylserine and phosphatidylethanolamine in
      mammalian cells.
AB  - Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are metabolically
      related membrane aminophospholipids. In mammalian cells, PS is required for
      targeting and function of several intracellular signaling proteins. Moreover, PS
      is asymmetrically distributed in the plasma membrane. Although PS is highly
      enriched in the cytoplasmic leaflet of plasma membranes, PS exposure on the cell
      surface initiates blood clotting and removal of apoptotic cells. PS is
      synthesized in mammalian cells by two distinct PS synthases that exchange serine
      for choline or ethanolamine in phosphatidylcholine (PC) or PE, respectively.
      Targeted disruption of each PS synthase individually in mice demonstrated that
      neither enzyme is required for viability whereas elimination of both synthases
      was embryonic lethal. Thus, mammalian cells require a threshold amount of PS. PE
      is synthesized in mammalian cells by four different pathways, the quantitatively
      most important of which are the CDP-ethanolamine pathway that produces PE in the
      ER, and PS decarboxylation that occurs in mitochondria. PS is made in ER
      membranes and is imported into mitochondria for decarboxylation to PE via a
      domain of the ER [mitochondria-associated membranes (MAM)] that transiently
      associates with mitochondria. Elimination of PS decarboxylase in mice caused
      mitochondrial defects and embryonic lethality. Global elimination of the CDP
      ethanolamine pathway was also incompatible with mouse survival. Thus, PE made by
      each of these pathways has independent and necessary functions. In mammals PE is
      a substrate for methylation to PC in the liver, a substrate for anandamide
      synthesis, and supplies ethanolamine for glycosylphosphatidylinositol anchors of
      cell-surface signaling proteins. Thus, PS and PE participate in many previously
      unanticipated facets of mammalian cell biology. This article is part of a Special
      Issue entitled Phospholipids and Phospholipid Metabolism.

PMID- 22960355
TI  - Drug induced phospholipidosis: an acquired lysosomal storage disorder.
AB  - There is a strong association between lysosome enzyme deficiencies and monogenic
      disorders resulting in lysosomal storage disease. Of the more than 75
      characterized lysosomal proteins, two thirds are directly linked to inherited
      diseases of metabolism. Only one lysosomal storage disease, Niemann-Pick disease,
      is associated with impaired phospholipid metabolism. However, other
      phospholipases are found in the lysosome but remain poorly characterized. A
      recent exception is lysosomal phospholipase A2 (group XV phospholipase A2).
      Although no inherited disorder of lysosomal phospholipid metabolism has yet been
      associated with a loss of function of this lipase, this enzyme may be a target
      for an acquired form of lysosomal storage, drug induced phospholipidosis. This
      article is part of a Special Issue entitled Phospholipids and Phospholipid
      Metabolism.

PMID- 22960357
TI  - Collagen--emerging collagen based therapies hit the patient.
AB  - The choice of biomaterials available for regenerative medicine continues to grow
      rapidly, with new materials often claiming advantages over the short-comings of
      those already in existence. Going back to nature, collagen is one of the most
      abundant proteins in mammals and its role is essential to our way of life. It can
      therefore be obtained from many sources including porcine, bovine, equine or
      human and offer a great promise as a biomimetic scaffold for regenerative
      medicine. Using naturally derived collagen, extracellular matrices (ECMs), as
      surgical materials have become established practice for a number of years. For
      clinical use the goal has been to preserve as much of the composition and
      structure of the ECM as possible without adverse effects to the recipient. This
      review will therefore cover in-depth both naturally and synthetically produced
      collagen matrices. Furthermore the production of more sophisticated three
      dimensional collagen scaffolds that provide cues at nano-, micro- and meso-scale
      for molecules, cells, proteins and bulk fluids by inducing fibrils alignments,
      embossing and layered configuration through the application of plastic
      compression technology will be discussed in details. This review will also shed
      light on both naturally and synthetically derived collagen products that have
      been available in the market for several purposes including neural repair, as
      cosmetic for the treatment of dermatologic defects, haemostatic agents, mucosal
      wound dressing and guided bone regeneration membrane. There are other several
      potential applications of collagen still under investigations and they are also
      covered in this review.

PMID- 22960359
TI  - Interactions between the vestibular nucleus and the dorsal cochlear nucleus:
      implications for tinnitus.
AB  - The peripheral auditory and vestibular systems are recognised to be closely
      related anatomically and physiologically; however, less well understood is the
      interaction of these two sensory systems in the brain. A number of previous
      studies in different species have reported that the dorsal and ventral cochlear
      nuclei receive direct projections from the primary vestibular nerve and one
      previous study had reported projections from the vestibular nucleus to the dorsal
      cochlear nucleus (DCN) in rabbit. Recently, Barker et al. (2012 PLoS One. 7(5):
      e35955) have reported new evidence that the lateral vestibular nucleus (LVN)
      projects to the DCN in rat and that these synapses are mediated by glutamate
      acting on AMPA and NMDA receptors. These recent findings, in addition to the
      earlier ones, suggest that the auditory and vestibular systems may be intimately
      connected centrally as well as peripherally and this may have important
      implications for disorders such as tinnitus.

PMID- 22960356
TI  - Mesenchymal-epithelial interactions during hair follicle morphogenesis and
      cycling.
AB  - Embryonic hair follicle induction and formation are regulated by mesenchymal
      epithelial interactions between specialized dermal cells and epidermal stem cells
      that switch to a hair fate. Similarly, during postnatal hair growth,
      communication between mesenchymal dermal papilla cells and surrounding epithelial
      matrix cells coordinates hair shaft production. Adult hair follicle regeneration
      in the hair cycle again is thought to be controlled by activating signals
      originating from the mesenchymal compartment and acting on hair follicle stem
      cells. Although many signaling pathways are implicated in hair follicle formation
      and growth, the precise nature, timing, and intersection of these inductive and
      regulatory signals remains elusive. The goal of this review is to summarize our
      current understanding and to discuss recent new insights into mesenchymal
      epithelial interactions during hair follicle morphogenesis and cycling.

PMID- 22960358
TI  - Alcohol-induced alterations in maternal uterine endothelial proteome: a
      quantitative iTRAQ mass spectrometric approach.
AB  - OBJECTIVE: To quantitate alcohol-induced alterations in the maternal uterine
      endothelial proteome utilizing iTRAQ-based mass spectrometry. STUDY DESIGN:
      Uterine artery endothelial cells from third trimester pregnant ewes were FAC
      sorted, validated and treated without or with binge-like alcohol. Lysates were
      trypsin digested, iTRAQ-labeled, and analyzed using nano LC MS/MS. RESULTS:
      Alcohol significantly upregulated 14 and downregulated 17 proteins (P<0.05)
      including those related to cell structure, transcription/translation regulation,
      histones, Ca(2+)/NO, and redox balance. Gene Ontology and ArrayTrack analyses
      revealed alterations to protein processing, binding, and nutrient metabolism
      pathways. Further, alcohol altered proteins previously correlated with fetal
      alcohol spectrum disorders (FASD) and those that regulate epigenetic,
      transcriptional, and translational processes. CONCLUSIONS: Alcohol differentially
      alters the proteome in the maternal uterine compartment at the level of the
      endothelium. iTRAQ mass spectrometry provides a robust high throughput platform
      to comprehend the multi-mechanistic actions of alcohol and develop appropriate
      biomarkers and ameliorative measures for FASD.

PMID- 22960360
TI  - Association of the CR1 polymorphism with late-onset Alzheimer's disease in
      Chinese Han populations: a meta-analysis.
AB  - It is well known that genetic variants play a critical role in the pathogenesis
      of Alzheimer's disease (AD). In 2009, a genome-wide association study (GWAS)
      demonstrated that a single nucleotide polymorphism (SNP), rs6656401, in
      complement receptor 1 (CR1) is significantly associated with late-onset
      Alzheimer's disease (LOAD) in Caucasian population. Subsequently, other
      researchers have attempted to validate this finding in Chinese Han populations.
      However, these findings in Chinese Han populations have produced both negative
      and positive results. To derive a more precise estimation for the relationship,
      we performed the present meta-analysis by analyzing three published association
      studies involving CR1 SNP rs6656401 through the use of the RevMan (v.5.1)
      program. Pooled odds ratios (ORs) were calculated for allele contrasts (A vs. G)
      and a dominant model [(AA+AG) vs. GG] in three studies that included 1019 cases
      and 1080 controls, respectively. The statistical results showed a significant
      difference between patients and controls for the A allele of CR1 SNP rs6656401
      (P=0.005). In addition, carriers of the A allele (AA+AG) of rs6656401 had a 1.69
      fold increased risk for LOAD compared with non-carriers (GG) (P=0.01). In
      conclusion, despite there are some limitations, this meta-analysis indicates that
      the A allele of the CR1 SNP rs6656401 is significantly associated with LOAD
      susceptibility in Chinese Han populations.

PMID- 22960361
TI  - Central anti-diabetic action of biguanide and thizolidinediones in D-glucose fed
      and streptozotocin-treated mouse models.
AB  - BACKGROUND: In the present study, the possible anti-diabetic action of biguanide
      and thiazolidinediones administered supraspinally or spinally was studied in ICR
      mice. METHODS: Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.)
      treated with 20 or 30 MUg metformin, pioglitazone and rosiglitazone in d-glucose
      fed and streptozotocin-treated models, and blood glucose levels was measured at
      30, 60 and 120 min after i.c.v. or i.t. administration. RESULTS: We found that
      i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood
      glucose level in d-glucose fed model, whereas pioglitazone showed no effect on
      the blood glucose level in d-glucose fed model. The i.t. administration with
      metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in
      d-glucose fed model. We also assessed the possible roles of biguanide and
      thiazolidinedione in the regulation of the blood glucose level in streptozotocin
      treated model. We found in the present study that i.c.v. or i.t. administration
      with metformin caused a pronounced attenuation of the blood glucose level in
      streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not
      affect the blood glucose level in streptozotocin-treated model. CONCLUSIONS: Our
      results suggest that the anti-diabetic actions of metformin and rosiglitazone
      appear to be mediated via the brain regions as revealed in d-glucose fed animal
      model. Furthermore, metformin administered supraspinally or spinally may be
      effective for treating type I diabetes mellitus as revealed in streptozotocin
      treated mouse model.

PMID- 22960362
TI  - Novel and recurrent spastin mutations in a large series of SPG4 Italian families.
AB  - BACKGROUND: Hereditary spastic paraplegias (HSP) are heterogeneous
      neurodegenerative disorders, genetically classified according to the identified
      disease gene or locus. Clinically, HSP are distinguished in pure and complicated
      forms. Mutations in the spastin gene (SPAST) are responsible for SPG4 and account
      approximately for 50% of the dominantly inherited paraplegias with a pure HSP
      phenotype. METHODS: Molecular screening of the SPAST gene allowed the
      identification of 31 Italian mutation carriers, from 19 unrelated families.
      Genetic testing was performed by direct sequencing and multiplex ligation
      dependent probe amplification. Subjects carrying SPAST mutations were
      retrospectively evaluated for clinical phenotype and disability score assessment.
      RESULTS: We found 12 recurrent mutations, and 7 novel SPAST mutations. Twenty
      eight patients exhibited a pure spastic paraplegia phenotype, while 3 subjects
      were asymptomatic mutation carriers. Four patients were sporadic cases. Age at
      onset ranged from 10 to 61 years. Disability score increased with age at
      examination and disease duration. Patients with onset >38 years presented a
      faster disease progression, and a higher disability functional index, than the
      patients with earlier onset (p<0.04). CONCLUSIONS: Our study enlarges the number
      of pathogenic SPAST mutations, and confirms the association with a pure spastic
      paraplegia phenotype. Age at onset was highly variable and correlates with the
      rate of disease progression. Future longitudinal clinical studies are needed to
      confirm these observations.

PMID- 22960363
TI  - Int6 silencing causes induction of angiogenic factors in neuronal cells via
      accumulation of hypoxia-inducible factor 2alpha and decreases brain damage in
      rats.
AB  - We have previously shown that when siRNA against Int6 (siRNA-Int6) was used,
      hypoxia-inducible factor 2alpha (HIF2alpha) activity was stabilized even under
      normoxic conditions, and the expression of several angiogenic factors was
      increased. In neuronal tissues, the mechanism underlying angiogenesis remains
      largely unknown. In the current study, we investigate the role of the tumor
      suppressor Int6/eIF3e in the regulation of the expression of angiogenic factors
      in neuronal cells. In addition, we test whether siRNA-Int6 reduces cold-induced
      brain damage in rats. We used human neuroblastoma SHSY5Y cells transfected with
      either siRNA-Int6, or a negative control siRNA. Real-time PCR and supersensitive
      multiplex assay were used to detect gene and protein expression of several
      angiogenic factors after transfection. For the animal studies, Wistar rats were
      subjected to brain damage by cold injury, and 50 MUg siRNA-Int6, 100 MUg siRNA
      Int6, or negative control was administrated. At day 7 post-treatment, brain
      sections were stained and image analysis system was used to determine the damaged
      area. Our experiments using SHSY5Y cells revealed a significant effect of siRNA
      Int6 on the expression of HIF2alpha but not HIF1alpha, both at 8 and 24h after
      transfection. The siRNA-Int6 led to significant up-regulation of angiogenic
      factors, including vascular endothelial growth factor and platelet-derived growth
      factor-B, both at the mRNA and protein levels. Furthermore, our animal studies
      revealed significantly reduced area of cold-induced damage in rats receiving
      siRNA-Int6, compared to negative controls. Our findings indicate that Int6 act as
      a hypoxia-independent master switch of angiogenesis in neuronal cells, and that
      inhibition of Int6 by siRNA may be an effective therapeutic strategy in treating
      ischemic diseases such as brain ischemia and injury.

PMID- 22960364
TI  - Uremic anorexia and ghrelin expression in the amygdala.
AB  - BACKGROUND/AIMS: Ghrelin can act as a signal for mealtime hunger and meal
      initiation. Amygdala is indispensable in appetitive behavior motivated by learned
      emotions. This study was to investigate the alteration of ghrelin in the amygdala
      of rats with chronic renal failure (CRF) and its relation with uremic anorexia.
      METHODS: SD rats were randomly classified into CRF group and control group (n=16
      per group). The CRF model was constructed using 5/6 nephrectomy. When plasma
      creatinine (PCr) and blood urea nitrogen (BUN) in the CRF group were twice more
      than the normal level, food intake (g/24h) was measured and then all rats were
      killed for detection of ghrelin protein expression in the amygdala using
      immunohistochemical analysis and mRNA expression using RT-PCT. Statistics was
      conducted with one-way analysis of variance, Student-Newman-Keuls-q test and
      correlation analysis. RESULTS: By the 8th week after the surgery, the BUN and PCr
      of CRF rats exceeded double the normal level, and their food intake was obviously
      decreased compared with the controls (P<0.05). The protein and mRNA expression of
      ghrelin in the amygdala of CRF group were significantly reduced, and there was a
      positive correlation between this reduction and the decrease in food intake
      (P<0.05). CONCLUSION: The reduction of amygdala's ghrelin in CRF rats may be
      associated with uremic anorexia.

PMID- 22960365
TI  - PBDE and PCB accumulation in benthos near marine wastewater outfalls: the role of
      sediment organic carbon.
AB  - Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were
      measured in sediments and benthic invertebrates near submarine municipal outfalls
      in Victoria and Vancouver, B.C., Canada, two areas with contrasting receiving
      environments. PBDE concentrations in wastewater exceeded those of the legacy PCBs
      by eight times at Vancouver and 35 times at Victoria. Total PBDE concentrations
      in benthic invertebrates were higher near Vancouver than Victoria, despite lower
      concentrations in sediments, and correlated with organic carbon-normalized
      concentrations in sediment. Principal Components Analysis indicated uptake of
      individual PBDE congeners was determined by sediment properties (organic carbon,
      grain size), while PCB congener uptake was governed by physico-chemical
      properties (octanol-water partitioning coefficient). Results suggest the utility
      of sediment quality guidelines for PBDEs and likely PCBs benefit if based on
      organic carbon-normalized concentrations. Also, where enhanced wastewater
      treatment increases the PBDEs to particulate organic carbon ratio in effluent,
      nearfield benthic invertebrates may face increased PBDE accumulation.

PMID- 22960366
TI  - Short-term molecular-level effects of silver nanoparticle exposure on the
      earthworm, Eisenia fetida.
AB  - Short-term changes in levels of expression of nine stress response genes and
      oxidative damage of proteins were examined in Eisenia fetida exposed to
      polyvinylpyrrolidone (PVP) coated Ag nanoparticles (Ag-NP) and AgNO(3) in natural
      soils. The responses varied significantly among days with the highest number of
      significant changes occurring on day three. Similarity in gene expression
      patterns between Ag-NPs and AgNO(3) and significant relationships of expression
      of CAT and HSP70 with Ag soil concentration suggest similarity in toxicity
      mechanisms of Ag ions and NPs. Significant increases in the levels of protein
      carbonyls on day three of the exposure to both ions and Ag-NPs indicate that both
      treatments induced oxidative stress. Our results suggest that Ag ions drive short
      term toxicity of Ag-NPs in E. fetida. However, given that <15% of Ag in the NPs
      was oxidized in these soils, dissolution of Ag-NPs is likely to occur after or
      during their uptake.

PMID- 22960367
TI  - Correction of distal femoral valgus deformities in adolescents and young adults
      using minimally invasive fixator-assisted locking plating (FALP).
AB  - The treatment of distal femoral valgus deformities in skeletally mature patients
      might be a challenging surgical problem with significant morbidity. Treatment
      options are various and include osteotomy and external fixation, intramedullary
      nailing, and plating using standard and locking plates. We describe technical
      notes of minimally invasive technique of fixator-assisted plating using a
      supracondylar locking plate. During a period of 3 years, we operated on six
      patients (seven femurs) with distal femoral valgus deformities of different
      etiologies. All patients achieved correction of the deformities and started full
      weight bearing with radiographic evidence of union 6 weeks after correction. We
      believe that fixator-assisted locking plating has advantages over correction
      using external fixation and intramedullary nailing. This method of correction can
      be performed by a minimally invasive technique, precisely, and with minimal
      morbidity.

PMID- 22960368
TI  - Subcellular localization prediction for human internal and organelle membrane
      proteins with projected gene ontology scores.
AB  - The membrane proteins make up more than a third of all known human proteins. The
      subcellular localizations play a key role to elucidate the potential biological
      functions of these membrane proteins. Although the experimental approaches for
      determining protein subcellular localizations exist, they are usually costly and
      time consuming. Thus, computational predictions provided an alternative approach
      for determining the protein subcellular localizations. However, current
      subcellular location predictors are generally developed for globular proteins.
      They did not perform well for membrane proteins. In this paper, we proposed a
      novel prediction algorithm, namely Projected Gene Ontology Score, which
      introduces the Gene Ontology annotation as a descriptor of the protein. This
      algorithm could significantly improve the prediction accuracy for the subcellular
      localizations of membrane proteins. It can designate each protein to one of the
      eight different locations, while the existing algorithm only covers three
      locations. Actually, the biological problem considered by our algorithm goes one
      level deeper than the existing algorithms. In addition, our algorithm can provide
      more than one location for the testing protein, which could be very useful in
      practical studies. Our algorithm is expected to be a good complement to the
      existing algorithms and has the potential to be extended to solve other problems.

PMID- 22960369
TI  - European Antibiotic Awareness Day 2012: getting smart about antibiotics, a public
      professional partnership.
AB  - November 18th 2012 is the fifth annual European Antibiotic Awareness Day (EAAD),
      an opportunity to raise public and professional awareness about the importance of
      prudent antibiotic use, and the threat of antibiotic resistance to public health.
      The aims of EAAD have been supported and reinforced by antibiotic stewardship
      campaigns across Europe, aimed at both healthcare professionals, and the public.
      Within the UK, antimicrobial stewardship is embedded within the Health and Social
      Care Act 2008, and is taken into account by the Care Quality Commission when
      making decisions about registration. The Department of Health Advisory Committee
      on Antimicrobial Resistance and Healthcare Associated Infection has recently
      produced guidance for antimicrobial stewardship in hospitals, 'Start Smart - then
      Focus', and the Royal College of General Practitioners has agreed antimicrobial
      stewardship as a clinical priority for 3 years, providing educational and audit
      materials, and tools to help general practitioners in patient consultations, to
      manage public demand for antibiotics when not clinically indicated. British
      Infection Association members need to be familiar with these initiatives and
      resources, and are encouraged to lead on local initiatives within their own
      workplaces and communities.

PMID- 22960370
TI  - Multiplex PCR of sonication fluid accurately differentiates between prosthetic
      joint infection and aseptic failure.
AB  - OBJECTIVE: Cultures have limited sensitivity in the diagnosis of prosthetic joint
      infection (PJI), especially in low-grade infections. We assessed the value of
      multiplex PCR in differentiating PJI from aseptic failure (AF). METHODS: Included
      were patients in whom the joint prosthesis was removed and submitted for
      sonication. The resulting sonication fluid was cultured and investigated by
      multiplex PCR, and compared with periprosthetic tissue culture. RESULTS: Among 86
      explanted prostheses (56 knee, 25 hip, 3 elbow and 2 shoulder prostheses), AF was
      diagnosed in 62 cases (72%) and PJI in 24 cases (28%). PJI was more common
      detected by multiplex PCR (n=23, 96%) than by periprosthetic tissue (n=17, 71%,
      p=0.031) or sonication fluid culture (n=16, 67%, p=0.016). Among 12 patients with
      PJI who previously received antibiotics, periprosthetic tissue cultures were
      positive in 8 cases (67%), sonication fluid cultures in 6 cases (50%) and
      multiplex PCR in 11 cases (92%). In AF cases, periprosthetic tissue grew
      organisms in 11% and sonication fluid in 10%, whereas multiplex PCR detected no
      organisms. CONCLUSIONS: Multiplex PCR of sonication fluid demonstrated high
      sensitivity (96%) and specificity (100%) for diagnosing PJI, providing good
      discriminative power towards AF, especially in patients previously receiving
      antibiotics.

PMID- 22960371
TI  - Choice between contingencies of variation: effects of the requirement of
      variation upon preference.
AB  - The present study investigated whether choices between contingencies of variation
      are affected by the degree of variability required. For such, five pigeons were
      exposed to a concurrent chain schedule. In the initial links, responses in one
      key initiated the terminal link with the most stringent variation requirement
      while responses in the other key initiated the terminal link with the least
      stringent variation requirement. In both terminal links, four-responses sequences
      were reinforced according to a variation criterion, which favored less frequent
      and less recent sequences. The probability of reinforcement in the terminal link
      with the least stringent criterion was manipulated in order to generate similar
      percentage and rate of reinforcers in both terminal links. Choices for the
      terminal link with the least stringent criterion were more frequent than choices
      for the terminal link with the most stringent criterion. It is possible that
      situations that demand lower levels of behavior variability are chosen due to the
      lower response cost correlated to those situations.

PMID- 22960372
TI  - Spark: a navigational paradigm for genomic data exploration.
AB  - Biologists possess the detailed knowledge critical for extracting biological
      insight from genome-wide data resources, and yet they are increasingly faced with
      nontrivial computational analysis challenges posed by genome-scale methodologies.
      To lower this computational barrier, particularly in the early data exploration
      phases, we have developed an interactive pattern discovery and visualization
      approach, Spark, designed with epigenomic data in mind. Here we demonstrate
      Spark's ability to reveal both known and novel epigenetic signatures, including a
      previously unappreciated binding association between the YY1 transcription factor
      and the corepressor CTBP2 in human embryonic stem cells.

PMID- 22960373
TI  - RNA sequencing reveals a diverse and dynamic repertoire of the Xenopus tropicalis
      transcriptome over development.
AB  - The Xenopus embryo has provided key insights into fate specification, the cell
      cycle, and other fundamental developmental and cellular processes, yet a
      comprehensive understanding of its transcriptome is lacking. Here, we used paired
      end RNA sequencing (RNA-seq) to explore the transcriptome of Xenopus tropicalis
      in 23 distinct developmental stages. We determined expression levels of all genes
      annotated in RefSeq and Ensembl and showed for the first time on a genome-wide
      scale that, despite a general state of transcriptional silence in the earliest
      stages of development, approximately 150 genes are transcribed prior to the
      midblastula transition. In addition, our splicing analysis uncovered more than
      10,000 novel splice junctions at each stage and revealed that many known genes
      have additional unannotated isoforms. Furthermore, we used Cufflinks to
      reconstruct transcripts from our RNA-seq data and found that ~13.5% of the final
      contigs are derived from novel transcribed regions, both within introns and in
      intergenic regions. We then developed a filtering pipeline to separate protein
      coding transcripts from noncoding RNAs and identified a confident set of 6686
      noncoding transcripts in 3859 genomic loci. Since the current reference genome,
      XenTro3, consists of hundreds of scaffolds instead of full chromosomes, we also
      performed de novo reconstruction of the transcriptome using Trinity and uncovered
      hundreds of transcripts that are missing from the genome. Collectively, our data
      will not only aid in completing the assembly of the Xenopus tropicalis genome but
      will also serve as a valuable resource for gene discovery and for unraveling the
      fundamental mechanisms of vertebrate embryogenesis.

PMID- 22960374
TI  - Sex-biased genetic effects on gene regulation in humans.
AB  - Human regulatory variation, reported as expression quantitative trait loci
      (eQTLs), contributes to differences between populations and tissues. The
      contribution of eQTLs to differences between sexes, however, has not been
      investigated to date. Here we explore regulatory variation in females and males
      and demonstrate that 12%-15% of autosomal eQTLs function in a sex-biased manner.
      We show that genes possessing sex-biased eQTLs are expressed at similar levels
      across the sexes and highlight cases of genes controlling sexually dimorphic and
      shared traits that are under the control of distinct regulatory elements in
      females and males. This study illustrates that sex provides important context
      that can modify the effects of functional genetic variants.

PMID- 22960376
TI  - Violence against doctors in China.

PMID- 22960377
TI  - Ordering the chaos for patients with multimorbidity.

PMID- 22960375
TI  - Genome-wide mapping of nucleosome positioning and DNA methylation within
      individual DNA molecules.
AB  - DNA methylation and nucleosome positioning work together to generate chromatin
      structures that regulate gene expression. Nucleosomes are typically mapped using
      nuclease digestion requiring significant amounts of material and varying enzyme
      concentrations. We have developed a method (NOMe-seq) that uses a GpC
      methyltransferase (M.CviPI) and next generation sequencing to generate a high
      resolution footprint of nucleosome positioning genome-wide using less than 1
      million cells while retaining endogenous DNA methylation information from the
      same DNA strand. Using a novel bioinformatics pipeline, we show a striking anti
      correlation between nucleosome occupancy and DNA methylation at CTCF regions that
      is not present at promoters. We further show that the extent of nucleosome
      depletion at promoters is directly correlated to expression level and can
      accommodate multiple nucleosomes and provide genome-wide evidence that expressed
      non-CpG island promoters are nucleosome-depleted. Importantly, NOMe-seq obtains
      DNA methylation and nucleosome positioning information from the same DNA
      molecule, giving the first genome-wide DNA methylation and nucleosome positioning
      correlation at the single molecule, and thus, single cell level, that can be used
      to monitor disease progression and response to therapy.

PMID- 22960378
TI  - Indian schoolchildren to undergo fitness tests amid fears of rising levels of
      obesity.

PMID- 22960379
TI  - Ear pain and facial palsy.

PMID- 22960381
TI  - Lysophosphatidic acid: chemical signature of neuropathic pain.
AB  - Acute inflammatory pain signal originates from transient hypersensitivity in
      afferent fibers when depolarized via injured tissues or proinflammatory cells
      derived pronociceptive ligand binding. This pain is sensitive to opioids and
      NSAIDs. In neuropathic pain, however, damage to the nerve along the pain pathway
      results in spontaneous generation of action potential and lowered nociceptive
      threshold, as seen in allodynia and hyperalgesia. This abnormal pain transmission
      had been linked to LPA production in the spinal cord, through activation of NMDA
      and NK1 activation by glutamate and SP in iPLA(2)/cPLA(2)/ATX-dependent pathway.
      In a bifurcated response involving G(q/11) and G(12/13) coupling, Schwann cell
      LPA(1) mediates degradation and transcriptional suppression of myelin proteins,
      respectively. The loss of contact inhibition on axonal growth creates
      cytoskeletal framework for axonal sprouting. LPA causes an amplification of LPA
      production through activation of LPA(3) signaling in microglia immediately after
      nerve injury. LPA(1) deficient mice (LPA(1)(-/-)) show no neuropathic-pain
      behavior or demyelination in response to intrathecal LPA injection or nerve
      injury. Given these bodies of research evidence, LPA therefore presents as the
      chemical signature for the initiation of neuropathic pain. This article is part
      of a Special Issue entitled Advances in Lysophospholipid Research.

PMID- 22960380
TI  - Phosphatidylethanolamine is externalized at the surface of microparticles.
AB  - Microparticles (MPs) are membrane-bound vesicles shed normally or as a result of
      various (pathological) stimuli. MPs contain a wealth of bio-active
      macromolecules. Aminophospholipid phosphatidylserine (PS) is present on the
      surface of many MPs. As PS and phosphatidylethanolamine (PE) are related, yet
      distinct aminophospholipids, the purpose of this study was to systematically and
      directly assess PE exposure on MPs. We examined MPs from various human cellular
      sources (human breast cancer, endothelial, red and white blood cells) by flow
      cytometry using a PE-specific probe, duramycin, and two PS-specific probes,
      annexin V and lactadherin. PS and PE exposure percentage was comparable on
      vascular and blood cell-derived MPs (80-90% of MP-gated events). However, the
      percentage of malignant breast cancer MPs exposing PE (~90%) was significantly
      higher than PS (~50%). Thus, while PS and PE exposure can result from a general
      loss of membrane asymmetry, there may also be distinct mechanisms of PE and PS
      exposure on MPs that vary by cellular source.

PMID- 22960382
TI  - Identification and characterization of a novel antimicrobial peptide from the
      venom of the ant Tetramorium bicarinatum.
AB  - A novel antimicrobial peptide, named Bicarinalin, has been isolated from the
      venom of the ant Tetramorium bicarinatum. Its amino acid sequence has been
      determined by de novo sequencing using mass spectrometry and by Edman
      degradation. Bicarinalin contained 20 amino acid residues and was C-terminally
      amidated as the majority of antimicrobial peptides isolated to date from insect
      venoms. Interestingly, this peptide had a linear structure and exhibited no
      meaningful similarity with any known peptides. Antibacterial activities against
      Staphylococcus aureus and S. xylosus strains were evaluated using a synthetic
      replicate. Bicarinalin had a potent and broad antibacterial activity of the same
      magnitude as Melittin and other hymenopteran antimicrobial peptides such as
      Pilosulin or Defensin. Moreover, this antimicrobial peptide has a weak hemolytic
      activity compared to Melittin on erythrocytes, suggesting potential for
      development into an anti-infective agent for use against emerging antibiotic
      resistant pathogens.

PMID- 22960383
TI  - Percutaneous coronary intervention among patients with left ventricular systolic
      dysfunction:  a review and meta-analysis of 19 clinical studies.
AB  - BACKGROUND: Coronary artery disease (CAD) is the most common cause for left
      ventricular dysfunction. Coronary artery bypass surgery (CABG) has not reduced
      mortality among patients with CAD and left ventricular systolic dysfunction
      receiving guideline-indicated pharmacological therapy. However, the benefit of
      percutaneous coronary intervention (PCI) among patients with left ventricular
      systolic dysfunction is not clear. OBJECTIVES: A meta-analysis of studies
      utilizing PCI among patients with left ventricular systolic dysfunction (ejection
      fraction <= 40%) was performed to determine in-hospital and long-term (>= 1 year)
      mortality. METHODS: A systematic computerized literature search was performed
      using the search terms 'poor left ventricle', 'percutaneous coronary
      intervention', 'revascularization', 'LV dysfunction' and 'heart failure'. Studies
      of patients undergoing PCI for CAD in the presence of left ventricular systolic
      dysfunction were included. Studies that did not report long-term mortality data
      and same-centre studies were excluded. RESULTS: In total, 4766 patients from 19
      studies were included in this meta-analysis. The mean (pooled estimate) age was
      65 years [95% confidence interval (CI) 62-68] with 80% (95% CI 75-84%) males. The
      mean (pooled estimate) ejection fraction was 30% (95% CI 27-33%). The in-hospital
      mortality using random-effects model (13 studies, total PCI n=2202) was 1.8%,
      n=39 (95% CI 1.0-2.9%). The long-term mortality (mean pooled estimate 24 months)
      using the random-effects model (19 studies, total follow-up n=2937) was 15.6%,
      n=401 (95% CI 11.0-20.7%). Five studies compared PCI versus CABG (n=455 vs.
      n=502) and provide long-term mortality data (deaths-PCI: n=102 vs. CABG: n=115).
      The relative risk using the random-effects model (PCI vs. CABG) was 0.98 (95% CI
      0.8-1.2, P=0.83). CONCLUSION: The present meta-analysis demonstrates that on the
      basis of available clinical studies, PCI among patients with left ventricular
      systolic dysfunction is feasible with acceptable in-hospital and long-term
      mortality and yields similar outcomes to CABG. However, neither intervention may
      improve outcome compared with pharmacological therapy alone.

PMID- 22960384
TI  - Anti-hyperglycemic effect of Potentilla discolor decoction on obese-diabetic (Ob
      db) mice and its chemical composition.
AB  - Potentilla discolor is used as an ethnomedicine in treatments of diabetes
      mellitus in China for years. In the present study, the anti-hyperglycemic effects
      of a clinical active extract (decoction) from P. discolor were investigated in Ob
      db mice. Four week's treatment of P. discolor decoction ameliorated the
      development of hyperlipidemia, lipid peroxidation and hyperglycemia associated
      with hyperphagia and polydypsia in Ob-db mice. P. discolor significantly
      attenuated the increase of blood glucose and cholesterol levels in Ob-db mice.
      These findings clearly provided evidences regarding the anti-hyperglycemic
      potentials of P. discolor decoction. High-resolution liquid chromatography-mass
      spectrometry/mass spectrometry (HR-LC-MS/MS) was used to analyze the
      phytochemicals in P. discolor decoction. In an comprehensive analysis of
      phytochemicals in P. discolor, thirty-five components were identified or
      characterized in P. discolor decoction and only sixteen of them have been
      reported in P. discolor previously. There are five major components identified in
      P. discolor decoction. One of the major components is a flavonoid sulfate, and
      this is the first evidence for the presences of sulfated flavonoid in P.
      discolor. Sulfated flavonoids have been reported to improve the complications of
      diabetes mellitus by inhibition of the aldose reductase in both experimental
      animals and clinical trials. Therefore, the sulfated flavonoid in P. discolor
      decoction may in part contribute to the anti-hyperglycemic effect of P. discolor.

PMID- 22960385
TI  - Pulmonary arterial hypertension in pediatric patients with hematopoietic stem
      cell transplant-associated thrombotic microangiopathy.
AB  - Pulmonary arterial hypertension (PAH) is rarely included in the differential
      diagnosis of cardiorespiratory failure after pediatric hematopoietic stem cell
      transplant (HSCT) as the clinical presentation is nonspecific and may mimic other
      etiologies. The pathogenesis of PAH in HSCT is poorly understood and the
      diagnosis requires a high degree of suspicion. We describe 5 children diagnosed
      with PAH after allogeneic HSCT. All 5 patients had prolonged clinical signs of
      transplantation-associated thrombotic microangiopathy (TA-TMA) when they
      presented with hypoxemic respiratory failure and evidence of PAH. Four of the 5
      patients had echocardiographic evidence of PAH, and 1 patient was diagnosed with
      PAH only on autopsy. PAH was diagnosed a median of 76 days (range, 56-101 days)
      after a diagnosis of TA-TMA. Despite aggressive medical management, including
      inhaled nitric oxide, 4 of the 5 patients died. One patient recovered from PAH
      after 11 months of sildenafil therapy. Three of the 4 deceased patients had an
      autopsy performed, demonstrating severe pulmonary vascular disease consistent
      with TA-TMA and severe PAH. We conclude that TA-TMA can be associated with
      significant pulmonary vascular injury presenting as hypoxemic respiratory failure
      with PAH after HSCT. Pediatric patients with unexplained hypoxemia after HSCT
      should be evaluated for both transplantation complications, TA-TMA and PAH,
      accordingly.

PMID- 22960386
TI  - Single cord blood combined with HLA-mismatched third party donor cells:
      comparable results to matched unrelated donor transplantation in high-risk
      patients with hematologic disorders.
AB  - Matched unrelated donor (MUD) transplantation is the first alternative in the
      absence of a matched sibling donor. For patients without a suitable adult donor,
      we have adopted the dual stem cell transplantation protocol consisting of cord
      blood (CB) in combination with CD34(+) cells from a third party HLA-mismatched
      donor. We analyzed the outcomes of patients undergoing both procedures in a
      single center. Starting in 2004, a total of 20 patients with high-risk disease
      underwent 22 dual transplants and 25 patients underwent myeloablative MUD
      transplantation. The 30-day cumulative incidence of neutrophil engraftment was
      similar in both groups (91% and 95%), with a median time to engraftment of 14 and
      16 days, respectively. Grade II-IV acute graft-versus-host disease was more
      frequent in the MUD group (40% versus 5%). Except for a tendency toward a higher
      incidence of viral hemorrhagic cystitis in the dual transplantation group,
      posttransplantation infectious events were comparable in the 2 groups. The 3-year
      cumulative incidence rates of relapse (41% versus 44%) and nonrelapse mortality
      (30% versus 25%) were similar in the MUD and dual transplantation cohorts.
      Estimated 3-year overall survival and disease-free survival were 47% and 41%,
      respectively, with no survival advantage for either group. In our experience,
      dual transplantation offers survival rates comparable to those from myeloablative
      MUD transplantation with similar nonrelapse mortality rates.

PMID- 22960387
TI  - Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients
      with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a
      GRAALL study.
AB  - We report here the results of the GRAAPH-2003 trial with long-term follow-up in
      45 patients with de novo Philadelphia chromosome-positive (Ph+) acute
      lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall
      survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001).
      Despite the selection in patients who actually underwent transplantation, these
      results suggest that allogeneic or autologous stem cell transplants (SCTs) still
      have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib
      therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a
      transplantation (9 patients), and 80% after autologous SCT (10 patients without
      allogeneic donor or >55 years, including 7 patients in complete molecular
      response).

PMID- 22960388
TI  - Survival differences between adolescents/young adults and children with B
      precursor acute lymphoblastic leukemia after allogeneic hematopoietic cell
      transplantation.
AB  - Risk-adapted therapy has been the cornerstone of treatment for pediatric B
      precursor acute lymphoblastic leukemia (B-ALL). Recently, age >= 13 years at
      diagnosis has been identified as a very high-risk feature for chemotherapy
      treated pediatric patients with B-ALL. Whether age at time of transplantation is
      associated with poor outcomes in adolescents and young adults (AYA) is unknown.
      We hypothesized that AYA receiving allogeneic hematopoietic cell transplantation
      (allo-HCT) would have greater relapse and inferior survival compared with
      children age <13 years. We reviewed the outcomes in 136 consecutive patients (age
      0-30 years) with B-ALL who underwent myeloablative allo-HCT at our institution,
      including 79 children age <13 years (58%) and 57 AYA age 13-30 years (42%).
      Overall survival at 5 years was significantly lower in the AYA group (hazard
      ratio, 1.74; 95% confidence interval [CI], 1.04-2.95; P = .03). In addition, the
      AYA patients had a greater risk of transplantation-related mortality at 1 year
      (hazard ratio, 2.23; 95% CI, 1.01-4.90; P = .05), but no difference in relapse
      (relative risk, 0.85; 95% CI, 0.41-1.76; P = .66). Based on this analysis, AYA
      patients undergoing allo-HCT for B-ALL have significantly inferior survival and
      greater transplantation-related mortality compared with children age <13 years,
      but no difference in relapse, suggesting that allo-HCT may overcome relapse in
      AYA. Further improvements in peritransplantation care are needed to limit
      complications in AYA patients.

PMID- 22960389
TI  - Effects of increased systolic Ca(2+) and beta-adrenergic stimulation on Ca(2+)
      transient decline in NOS1 knockout cardiac myocytes.
AB  - We have previously shown that the main factor responsible for the faster
      [Ca(2+)](i) decline rate with beta-adrenergic (beta-AR) stimulation is the
      phosphorylation of phospholamban (PLB) rather than the increase in systolic
      Ca(2+) levels. The purpose of this study was to correlate the extent of
      augmentation of PLB Serine(16) phosphorylation to the rate of [Ca(2+)](i)
      decline. Thus, ventricular myocytes were isolated from neuronal nitric oxide
      synthase knockout (NOS1(-/-)) mice, which we observed had lower basal PLB
      Serine(16) phosphorylation levels, but equal levels during beta-AR stimulation.
      Ca(2+) transients (Fluo-4) were measured in myocytes superfused with 3mM
      extracellular Ca(2+) ([Ca(2+)](o)) and a non-specific beta-AR agonist
      isoproterenol (ISO, 1MUM) with 1mM [Ca(2+)](o). This allowed us to get matched
      Ca(2+) transient amplitudes in the same myocyte. Similar to our previous work,
      Ca(2+) transient decline was significantly faster with ISO compared to 3mM
      [Ca(2+)](o), even with matched Ca(2+) transient amplitudes. Interestingly, when
      we compared the effects of ISO on Ca(2+) transient decline between NOS1(-/-) and
      WT myocytes, ISO had a larger effect in NOS1(-/-) myocytes, which resulted in a
      greater percent decrease in the Ca(2+) transient RT(50). We believe this is due
      to a greater augmentation of PLB Serine16 phosphorylation in these myocytes.
      Thus, our results suggest that not only the amount but the extent of augmentation
      of PLB Serine(16) phosphorylation are the major determinants for the Ca(2+)
      decline rate. Furthermore, our data suggest that the molecular mechanisms of
      Ca(2+) transient decline is normal in NOS1(-/-) myocytes and that the slow basal
      Ca(2+) transient decline is predominantly due to decreased PLB phosphorylation.

PMID- 22960390
TI  - Pharmacological evaluation of sedative-hypnotic activity and gastro-intestinal
      toxicity of Rhizoma Paridis saponins.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Paridis saponins (RPS) have been well
      studied for antimicrobial, anti-hemorrhagic, and anticancer effects. However,
      scientific information on RPS regarding the toxic and neuropharmacological
      effects is limited. In this study, the acute oral toxicity, sedative-hypnotic
      activity and gastro-intestinal toxicity of RPS were investigated. MATERIALS AND
      METHODS: The acute toxicity was carried out by administering single doses (800
      5000 mg/kg) of RPS to adult mice. Rotarod test and sodium pentobarbital-induced
      hypnosis activity were used to evaluate the neuropharmacological effects on mice.
      Gastric emptying and intestinal transit were used to investigate the gastric
      intestinal system effects. RESULTS: A single oral administration of RPS dose
      dependently caused adverse effects on the general behavior and mortality rate of
      mice. LD(50) value of oral acute toxicity was 2182.4 mg/kg, with 95% confidence
      limit of 1718.4-2807.8 mg/kg. In the test of sleeping mice, RPS acted in synergy
      with sodium pentobarbital at doses 250 and 500 mg/kg while motor coordination was
      not influenced within 120 min after treatment with RPS. Regarding the gastric
      intestinal toxicity, RPS (100, 250, and 500 mg/kg) significantly inhibited
      gastric emptying but did not affect the intestinal transit. CONCLUSIONS: RPS,
      which is a hypotoxic anticancer drug, possesses the sedative-hypnotic activity
      and gastric stimulus side effect.

PMID- 22960391
TI  - Tyrosine-1 and threonine-4 phosphorylation marks complete the RNA polymerase II
      CTD phospho-code.
AB  - Eukaryotic RNA polymerase II (RNAP II) has evolved an array of heptad repeats
      with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy
      terminal domain (CTD) of its largest subunit (Rpb1). Dynamic phosphorylation of
      Ser2, Ser5 and Ser7 residues orchestrates the binding of transcription and RNA
      processing factors to the transcription machinery. Recent studies show that the
      two remaining potential phosphorylation sites, tyrosine-1 and threonine-4, are
      phosphorylated as well and contribute to the previously proposed "CTD code". With
      the impairment of binding of CTD interacting factors, these novel phosphorylation
      marks add an accessory layer of regulation to the RNAP II transcription cycle.

PMID- 22960392
TI  - Developing leaders in priority populations to address tobacco disparities: 
      results from a leadership institute.
AB  - CONTEXT: Few published evaluations documenting the results of community health
      leadership programs exist. Furthermore, few leadership programs specifically
      address cross-cultural issues or priority populations, and none have focused on
      the area of tobacco control. OBJECTIVE: The goal of the evaluation was to
      determine the effectiveness of the Leadership and Advocacy Institute to Advance
      Minnesota's Parity for Priority Populations Institute. Institute Fellows were
      recruited from 5 priority populations, including African/African American,
      American Indian, Asian American, Chicano Latino and Lesbian, Gay, Bisexual, and
      Transgender. The Institute's impact on the acquisition and application of
      particular leadership skills was assessed, along with its impact in building
      priority population capacity to engage in tobacco control activities. DESIGN AND
      MEASURE: Findings are based on mixed methods, including Fellows' completion of
      paper surveys prior, during, and post-Institute, and telephone interviews
      conducted post-Institute. RESULTS: Perceived skills increased in all areas
      assessed. Fellows reported applying specific skills acquired 16 months after the
      Institute. Furthermore, a high number of Fellows were more intensely involved in
      tobacco control work compared to baseline and reported involvement in cross
      cultural collaborations or initiatives post-Institute. CONCLUSION: The Institute
      achieved both short-term and intermediate outcomes; skills were acquired during
      the Institute and sustained and applied in areas of tobacco control over 1 year
      later.

PMID- 22960393
TI  - [Clinical problems in medical mycology: problem number 45].
AB  - A 43 year-old diabetic woman, who suffered chronic cough and brown expectoration,
      is presented in this clinical problem. X-ray exam and CT thorax scan showed a
      cavitary lung lesion, located at the upper field of the left lung. This lesion
      had 5 cm in diameter, with a thick wall and a spherical shadow inside. The
      diagnosis of chronic cavitary pulmonary coccidioidomycosis was based on the
      isolation of Coccidioides sp. from cultures of expectoration and bronchoalveolar
      lavage, and the detection of specific antibodies in immunodiffusion test and
      counterimmunoelectrophoresis with coccidiodin. Her diabetes was not well
      controlled. She was treated with intravenous amphotericin B and oral
      itraconazole, with good clinical response; after four months of treatment the
      patient abandoned clinical controls. We suppose that the patient presented a
      coccidioidal fungus ball, inside a chronic cavitary lesion due to pulmonary
      coccidiodomycosis. She came from an endemic zone of coccidioidomycosis in the
      Northwest of the Argentine Republic (Catamarca Province).

PMID- 22960394
TI  - Comprehensive review on the HSC70 functions, interactions with related molecules
      and involvement in clinical diseases and therapeutic potential.
AB  - Heat shock cognate protein 70 (HSC70) is a constitutively expressed molecular
      chaperone which belongs to the heat shock protein 70 (HSP70) family. HSC70 shares
      some of the structural and functional similarity with HSP70. HSC70 also has
      different properties compared with HSP70 and other heat shock family members.
      HSC70 performs its full functions by the cooperation of co-chaperones. It
      interacts with many other molecules as well and regulates various cellular
      functions. It is also involved in various diseases and may become a biomarker for
      diagnosis and potential therapeutic targets for design, discovery, and
      development of novel drugs to treat various diseases. In this article, we provide
      a comprehensive review on HSC70 from the literatures including the basic general
      information such as classification, structure and cellular location, genetics and
      function, as well as its protein association and interaction with other proteins.
      In addition, we also discussed the relationship of HSC70 and related clinical
      diseases such as cancer, cardiovascular, neurological, hepatic and many other
      diseases and possible therapeutic potential and highlight the progress and
      prospects of research in this field. Understanding the functions of HSC70 and its
      interaction with other molecules will help us to reveal other novel properties of
      this protein. Scientists may be able to utilize this protein as a biomarker and
      therapeutic target to make significant advancement in scientific research and
      clinical setting in the future.

PMID- 22960396
TI  - Environmental nitrogen dioxide (NO2) exposure influences development and
      progression of ischemic stroke.
AB  - Here the correlativity between NO(2), a representative pollutant of vehicle
      exhaust, and ischemic stroke was first determined under experimental conditions
      following some epidemiological reports. First, we found that blood viscosity, red
      blood cell (RBC) aggregation-, electrophoresis- and rigidity-index in healthy
      rats were increased after exposure to 5mg/m(3) NO(2) for one- and three-month.
      Based on this, we set up stroke rat model and exposed them to NO(2) at the same
      concentration for one week, and found that NO(2) exposure time-dependently
      delayed neurological structure and function recovery of MCAO (middle cerebral
      artery occlusion) rat, and worsened pathological injuries and apoptosis induced
      by MCAO operation. Endothelial and inflammatory responses, two common cellular
      pathomechanisms involved in ischemic brain damage, were induced in cortex by MCAO
      treatment and exacerbated by followed NO(2) inhalation. Expression of the
      endothelial and inflammatory biomarkers in stroke displayed the same tendency in
      healthy rats after sub-acute and sub-chronic NO(2) exposure as in MCAO model in a
      concentration-dependent manner. Our data provide evidence that environmental
      NO(2) is an important inducer, and also a promoter of ischemic stroke, with
      endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2) and
      intercellular adhesion molecule 1 (ICAM-1) being potential indicators of this
      effect.

PMID- 22960395
TI  - Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for
      substance abuse disorders: evidence from the bench and the bedside.
AB  - Understanding substance use disorders (SUDs) and the problems associated with
      abstinence has grown in recent years. Nonetheless, highly efficacious treatment
      targeting relapse prevention has remained elusive, and there remains no FDA
      approved pharmacotherapy for psychostimulant dependence. Preclinical and clinical
      investigations assessing the utility of classical antidepressants, which block
      monoamine reuptake, show mixed and often contradictory results. Mirtazapine
      (Remeron(r)) is a unique FDA-approved antidepressant, with negligible affinity
      for reuptake proteins, indirectly augments monoamine transmission presumably
      through antagonist activity at multiple receptors including the norepinephrine
      (NE)(alpha2), and serotonin (5-HT)(2A/C) receptors. Historically, mirtazapine was
      also considered to be a 5-HT(2C) antagonist, but recent evidence indicates that
      mirtazapine is an inverse agonist at this receptor subtype. Suggesting a
      promising role for mixed-action serotonergic drugs for addiction pharmacotherapy,
      mirtazapine attenuates psychostimulant-induced behaviors in several rodent models
      of substance abuse, and antagonizes methamphetamine-induced biochemical and
      electrophysiological alterations in rats. Preclinical findings are confirmed
      through published case studies documenting successful outcomes with mirtazapine
      therapy across a number of SUDs. To date, a large scale clinical trial assessing
      the utility of mirtazapine in substance abuse pharmacotherapy has yet to be
      conducted. However, as reviewed here, accumulating preclinical and clinical
      evidence argues that mirtazapine, or compounds that emulate aspects of its
      pharmacological profile, may prove useful in helping treat addictions.

PMID- 22960397
TI  - How benzene and its metabolites affect human marrow derived mesenchymal stem
      cells.
AB  - Benzene is a known environmental pollutant with demonstrated leukemogenic
      activity. Marrow mesenchymal stem cells (MSCs), contribute to skeletal remodeling
      and repair. They also support haematopoiesis constructing important elements of
      haematopoietic niche. In the present study, the effects of a range of benzene
      concentrations along with those of its reactive metabolites, p-benzoquinone (BQ)
      and hydroquinone (HQ) on the viability of MSCs, apoptosis induction and
      caspase3/7 activity in these cells were analyzed. Our findings revealed that low
      concentrations of these chemicals (10MUM of benzene, 5MUM of either of BQ or HQ)
      significantly increase the number of chemically treated cells. Moreover, applied
      BQ/HQ concentrations were shown to be able to considerably inhibit caspase3/7
      activity. While in benzene exposure experiments, the lowest concentration
      triggered the greatest increase in caspase3/7 activity during the initial hours
      of exposure. On the other hand, MSCs exposure to higher concentrations of benzene
      (100MUM) and its metabolites, BQ/HQ (10MUM and 50MUM), can induce cell death
      after 24h of exposure mainly through apoptotic pathways. In addition, changes in
      the expression of six mRNAs due to being subjected to 10MUM of BQ or HQ and 50MUM
      of benzene were assessed. The genes under investigation were RUNX2, WNT5A, DKK1,
      JAG1, KITLG and CXCL12 which are expressed by MSCs playing roles in adipo
      osteogenic differentiation of MSCs and the regulation of haematopoiesis. The
      analysis exhibited a great augmentation in RUNX2 expression associated with DKK1
      and KITLG up-regulation. The results also indicated that treatment of cells with
      all three chemicals gives rise to down-regulation of JAG1 and treatment with both
      HQ and BQ triggers WNT5A over-expression. With regard to CXCL12, treatment with
      BQ caused slight up-regulation and treatment with HQ led to down-regulation. The
      alterations observed in the expression profile of genes could affect/modify the
      process of differentiation of MSCs into osteoblast. Other expected outcomes
      involve augmented canonical Wnt signaling activity in exposed cells with RUNX2
      overexpression as the indicator which is probably forced to decrease to the
      normal level via DKK1 and WNT5A up-regulation. RUNX2 overexpression in MSCs can
      also be indicative of the RUNX2 up-regulation in myeloid progenitors thereby its
      involvement in AML development due to benzene exposure. Observed changes in the
      expression of WNT5A, DKK1, KITLG, CXCL12 and JAG1 can lead to the disturbance of
      HSC niche resulting in haematopoietic failure and leukemia development. It is
      obvious that increased viability together with caspase3/7 inhibition could
      aggravate the adverse effects of exposure to these chemicals.

PMID- 22960398
TI  - The role of the heterochronic microRNA let-7 in the progression of aging.
AB  - Aging results in reduced tissue homeostasis and declined ability to replace
      damaged cells by new functional ones. In many tissues, homeostasis and repair are
      supported by tissue-specific stem cells that induce to generate differentiated
      cells in accordance with physiological requirements. Heterochronic genes,
      initially described in worms, specify the timing of fate decisions in each cell
      type and thus ensure a synchronized program of development throughout the animal.
      The heterochronic let-7 microRNA plays an important role in development by
      repressing cell fate regulators to promote stage progression. Recent studies
      reveal a new role of let-7 which occurs much later in life and regulates aging of
      several tissues, across species. In this article I review the current knowledge
      on the fate mechanisms of tissue stem cells during aging that are modulate by let
      7, as well as its co-partners and its target genes. I also discuss the
      therapeutic potential of controlling heterochronic events as a possible treatment
      for aging-related disorders. Timing is a clear dimension of organisms'
      development that may be difficult to witness in aging stages that are not as
      defined as in embryonic development. Exploring the regulation of stem cell aging
      by let-7 may ultimately reveal novel timing mechanisms.

PMID- 22960399
TI  - HMGB1 and RAGE levels in induced sputum correlate with asthma severity and
      neutrophil percentage.
AB  - Previous work indicated that high mobility group box-1 (HMGB1) protein may be
      involved in neutrophilic asthma. Here, we sought to investigate the correlation
      between HMGB1 and one of its receptors, receptor for advanced glycosylation end
      products (RAGE), with the severity of bronchial asthma. Compared to the control
      group (30 healthy individuals), patients in the asthma group (n=72) exhibited a
      higher percentage of neutrophils and higher HMGB1 and RAGE levels in induced
      sputum samples (P<0.05). Concurrently, FEV(1)% was significantly lower in the
      asthma group (P<0.05). Further, compared to mild and moderate asthma, in patients
      with severe asthma ACQ scores, the percentage of neutrophils, and HMGB1 levels
      were significantly higher, while FEV(1)% was significantly lower (P<0.05). The
      percentage of neutrophils and HMGB1 and RAGE levels were lower after treatment
      than before treatment (P<0.05). Finally, negative correlations were observed
      between HMGB1 or RAGE levels and FEV(1)% (r=-0.777 and r=-0.291, P<0.05), and
      positive correlations were detected between HMGB1 or RAGE levels and percentage
      of neutrophils (r=0.803 and r=0.326, P<0.05). Additionally, positive correlations
      were observed between HMGB1 and RAGE levels within the asthma group (r=0.306,
      P<0.05). Therefore, HMGB1 protein levels correlate with the severity of asthma,
      and HMGB1 may contribute to the inflammatory process of asthma.

PMID- 22960400
TI  - Molecular characterization, metal uptake and copper induced transcriptional
      activation of efflux determinants in copper resistant isolates of Klebsiella
      pneumoniae.
AB  - An efflux system, comprising cus determinants, plays an important role in pumping
      out this metal in gram negative bacteria exposed to high concentration of copper.
      Cus determinants comprise two operons, one regulatory (cusRS) and the other
      structural (cusCFBA). Although the efflux system has been described in quite a
      few members of Enterobacteriaceae, little is known about this system in
      Klebsiella spp. We are describing cus determinants in Klebsiella pneumoniae for
      the first time and also providing evidence for their metal-induced expression,
      both under aerobic and anaerobic conditions. Copper resistant K. pneumoniae,
      capable of copper uptake and later efflux of excessive copper, was isolated from
      industrial waste water. Expression of both cusRS and cusCFBA was quantified at
      transcriptional level through real time PCR. The results demonstrated that cus
      determinants were functional under both aerobic and anaerobic conditions. The
      mRNA level of both operons increased several fold in the presence of non-lethal
      as well as sub-lethal copper concentrations. The increase in cusCFBA transcripts
      was 74.8 fold 15 min after exposure to 3mM Cu(++) under aerobic conditions
      compared to the 16 fold increase in cusRS under the same conditions. Under
      anaerobic conditions the cusCFBA transcripts increased 32.65 fold and the cusRS
      five fold within 15 min after exposure to 3mM Cu(++). It is concluded that cus
      genetic determinants in K. pneumoniae comprise structural component (cusCFBA) and
      a regulatory component (cusRS), which show several fold expression under copper
      induction both under aerobic and anaerobic conditions. Under aerobic conditions,
      the structural genes express 4.7 fold more than the regulatory genes, whereas
      under anaerobic conditions, this expression is 6.5 fold. Finally, time course
      study revealed a novel pattern of immediate up-regulated expression followed by
      decreased and another increased in the transcript level of both operons of cus
      determinants in the presence of copper.

PMID- 22960401
TI  - A unique tRNA gene family and a novel, highly expressed ORF in the mitochondrial
      genome of the silver-lip pearl oyster, Pinctada maxima (Bivalvia: Pteriidae).
AB  - Characteristics of mitochondrial (mt) DNA such as gene content and arrangement,
      as well as mt tRNA secondary structure, are frequently used in comparative
      genomic analyses because they provide valuable phylogenetic information. However,
      most analyses do not characterize the relationship of tRNA genes from the same mt
      genome and, in some cases, analyses overlook possible novel open reading frames
      (ORFs) when the 13 expected protein-coding genes are already annotated. In this
      study, we describe the sequence and characterization of the complete mt genome of
      the silver-lip pearl oyster, Pinctada maxima. The 16,994-bp mt genome contains
      the same 13 protein-coding genes (PCGs) and two ribosomal RNA genes typical of
      metazoans. The gene arrangement, however, is completely distinct from that of all
      other available bivalve mt genomes, and a unique tRNA gene family is observed in
      this genome. The unique tRNA gene family includes two trnS(-AGY) and trnQ genes,
      a trnM isomerism, but it lacks trnS(-CUN). We also report the first clear
      evidence of alloacceptor tRNA gene recruitment (trnP->trnS(-AGY)) in mollusks. In
      addition, a novel ORF (orfUR1) expressed at high levels is present in the mt
      genome of this pearl oyster. This gene contains a conserved domain,
      "Oxidored_q1_N", which is a member of Complex I and thus may play an important
      role in key biological functions. Because orfUR1 has a very similar nucleotide
      composition and codon bias to that of other genes in this genome, we hypothesize
      that this gene may have been moved to the mt genome via gene transfer from the
      nuclear genome at an early stage of speciation of P. maxima, or it may have
      evolved as a result of gene duplication, followed by rapid sequence divergence.
      Lastly, a 319-bp region was identified as the possible control region (CR) even
      though it does not correspond to the longest non-coding region in the genome.
      Unlike other studies of mt genomes, this study compares the evolutionary patterns
      of all available bivalve mt tRNA and atp8 genes.

PMID- 22960402
TI  - Waste-water impacts on groundwater: Cl/Br ratios and implications for arsenic
      pollution of groundwater in the Bengal Basin and Red River Basin, Vietnam.
AB  - Across West Bengal and Bangladesh, concentrations of Cl in much groundwater
      exceed the natural, upper limit of 10 mg/L. The Cl/Br mass ratios in groundwaters
      range up to 2500 and scatter along mixing lines between waste-water and dilute
      groundwater, with many falling near the mean end-member value for waste-water of
      1561 at 126 mg/L Cl. Values of Cl/Br exceed the seawater ratio of 288 in uncommon
      NO(3)-bearing groundwaters, and in those containing measurable amounts of salt
      corrected SO(4) (SO(4) corrected for marine salt). The data show that shallow
      groundwater tapped by tube-wells in the Bengal Basin has been widely contaminated
      by waste-water derived from pit latrines, septic tanks, and other methods of
      sanitary disposal, although reducing conditions in the aquifers have removed most
      evidence of NO(3) additions from these sources, and much evidence of their
      additions of SO(4). In groundwaters from wells in palaeo-channel settings, end
      member modelling shows that >25% of wells yield water that comprises >=10% of
      waste-water. In palaeo-interfluvial settings, only wells at the margins of the
      palaeo-interfluvial sequence contain detectable waste water. Settings are
      identifiable by well-colour survey, owner information, water composition, and
      drilling. Values of Cl/Br and faecal coliform counts are both inversely related
      to concentrations of pollutant As in groundwater, suggesting that waste-water
      contributions to groundwater in the near-field of septic-tanks and pit-latrines
      (within 30 m) suppress the mechanism of As-pollution and lessen the prevalence
      and severity of As pollution. In the far-field of such sources, organic matter in
      waste-water may increase groundwater pollution by As.

PMID- 22960403
TI  - [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, augments the
      effects of orally delivered exenatide and pramlintide acetate on energy balance
      and glycemic control in insulin-resistant male C57BLK/6-m db/db mice.
AB  - The escalation predicted for the incidence of both type 2 diabetes mellitus and
      obesity has prompted investigators to search for additional pharmacotherapeutic
      approaches to their treatment. Two of these approaches, combination
      pharmacotherapy and utilization of leptin-related bioactive synthetic peptides as
      anti-diabetes/anti-obesity agents, were used in the present study. Exenatide or
      pramlintide acetate was reconstituted in dodecyl maltoside (DDM) in the absence
      or presence of [D-Leu-4]-OB3, and delivered orally by gavage to insulin-resistant
      male C57BLK/6-m db/db mice twice daily for 14 days. Body weight gain, food and
      water intake, blood glucose, and serum insulin levels were measured. Mice given
      DDM alone for 14 days were 19.7% heavier than they were at the beginning of the
      study, while oral delivery of exenatide or [D-Leu-4]-OB3 in DDM reduced body
      weight gain to only 13.9% and 11.5%, respectively, of initial body weight. Mice
      receiving exenatide and [D-Leu-4]-OB3 were 4.2% lighter than they were at the
      beginning of the study. In another study, Intravail(r) treated control mice
      gained 38.2% of their initial body weight, while mice receiving pramlintide
      acetate or [D-Leu-4]-OB3 were only 26.8% and 25.4% heavier, respectively, at the
      end of the study, Co-administration of pramlintide acetate and [D-Leu-4]-OB3 did
      not further enhance the effect of pramlintide acetate on body weight gain. Food
      intake was reduced by exenatide, pramlintide acetate, and [D-Leu-4]-OB3 alone,
      and co-delivery with [D-Leu-4]-OB3 did not induce a further decrease. Water
      intake was not affected by exenatide, pramlintide acetate, or [D-Leu-4]-OB3
      alone, but co-delivery of exenatide or pramlintide acetate with [D-Leu-4]-OB3
      resulted in a significant reduction in water intake. Oral delivery of exenatide
      or pramlintide acetate in DDM significantly lowered blood glucose levels by 20.4%
      and 30.2%, respectively. Co-delivery with [D-Leu-4]-OB3 further reduced blood
      glucose by 38.3% and 50.5%, respectively. A concentration-dependent increase in
      serum insulin was observed in response to increasing concentrations of exenatide,
      and [D-Leu-4]-OB3 slightly reduced the insulin response to exenatide at all
      concentrations tested. Increasing concentrations of pramlintide acetate alone did
      not elevate serum insulin, and when given in combination with [D-Leu-4]-OB3,
      serum insulin levels fell below those of DDM-treated control mice. Our data
      indicate that (1) exenatide and pramlintide acetate, currently administered by
      subcutaneous injection, can be given orally in DDM; (2) the bioactivity of
      exenatide and pramlintide acetate is retained following oral delivery in DDM; and
      (3) the effects of exenatide and pramlintide acetate on energy balance and
      glycemic control can be enhanced by co-administration with [D-Leu-4]-OB3, a
      synthetic peptide amide with leptin-like activity.

PMID- 22960404
TI  - Acute response of hypophysiotropic thyrotropin releasing hormone neurons and
      thyrotropin release to behavioral paradigms producing varying intensities of
      stress and physical activity.
AB  - The activity of the hypothalamus-pituitary-thyroid (HPT) axis is essential for
      energy homeostasis and is differentially modulated by physical and by
      psychological stress. Contradictory effects of stressful behavioral paradigms on
      TSH or thyroid hormone release are due to type, length and controllability of the
      stressor. We hypothesized that an additional determinant of the activity of the
      HPT axis is the energy demand due to physical activity. We thus evaluated the
      response of thyrotropin releasing hormone (TRH) neurons of the hypothalamic
      paraventricular nucleus (PVN) in Wistar male rats submitted to the elevated plus
      maze (EPM), the open field test (OFT), or restraint, and sacrificed within 1h
      after test completion; the response to OFT was compared during light (L) or dark
      (D) phases. Locomotion and anxiety behaviors were similar if animals were tested
      in L or D phases but their relation to the biochemical parameters differed. All
      paradigms increased serum corticosterone concentration; the levels of
      corticotropin releasing hormone receptor 1 and of glucocorticoid receptor (GR)
      mRNAs in the PVN were enhanced after restraint or OFT-L. Levels of proTRH mRNA
      increased in the PVN after exposure to EPM-L or OFT-D; serum levels of
      thyrotropin (TSH) and T(4) only after OFT-D. In contrast, restraint decreased TRH
      mRNA and serum TSH levels, while it increased TRH content in the mediobasal
      hypothalamus, implying reduced release. Expression of proTRH in the PVN varied
      proportionally to the degree of locomotion in OFT-D, while inversely to anxiety
      in the EPM-L, and to corticosterone in EPM-L and OFT-D. TRH mRNA levels were
      analyzed by in situ hybridization in the rostral, middle and caudal zones of the
      PVN in response to OFT-D; they increased in the middle PVN, where most TRH
      hypophysiotropic neurons reside; levels correlated positively with the velocity
      attained in the periphery of the OF and negatively, with anxiety. Variations of
      serum TSH levels correlated positively with locomotor activity in EPM-L and OFT-L
      or -D, while negatively to serum corticosterone levels in all paradigms. These
      results support the proposal that the hypophysiotropic PVN TRH neurons are
      activated by short term physical activity but that this response may be blunted
      by the inhibitory effect of stress.

PMID- 22960405
TI  - Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog
      ROSE-010 delivered via pulmonary and systemic routes in the conscious rat.
AB  - BACKGROUND: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces
      gastrointestinal motility and relieves acute pain in patients with irritable
      bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is
      a reliable model of pharmacological effects on gastrointestinal motility.
      Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in
      gut musculature and its effectiveness when administered by pulmonary inhalation.
      MATERIALS AND METHODS: Rats were implanted with bipolar electrodes at 5, 15 and
      25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous
      or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 MUg/kg) with or
      without the GLP-1 receptor blocker exendin(9-39)amide (300 MUg/kg.h), were
      studied. Second, ROSE-010 (100, 200 MUg/kg) Technosphere(r) powder was studied by
      inhalation. RESULTS: The baseline MMC cycle length was 17.5+/-0.8 min. GLP-1 and
      ROSE-010, administered intravenously or subcutaneously, significantly inhibited
      myoelectric activity and prolonged MMC cycling; 100 MUg/kg completely inhibited
      spiking activity for 49.1+/-4.2 and 73.3+/-7.7 min, while the MMC cycle length
      increased to 131.1+/-11.4 and 149.3+/-15.5 min, respectively. Effects of both
      drugs were inhibited by exendin(9-39)amide. Insufflation of ROSE-010 (100, 200
      MUg/kg) powder formulation totally inhibited myoelectric spiking for 52.6+/-5.8
      and 70.1+/-5.4 min, and increased MMC cycle length to 102.6+/-18.3 and 105.9+/
      9.5 min, respectively. CONCLUSIONS: Pulmonary delivery of ROSE-010 inhibits gut
      motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor
      mediated inhibition of MMC comparable to that of intravenous or subcutaneous
      administration. This suggests that ROSE-010 administered as a Technosphere(r)
      inhalation powder has potential in IBS pain management and treatment.

PMID- 22960406
TI  - Prokineticin 2 is involved in the thermoregulation and energy expenditure.
AB  - Animals have developed adaptive strategies to survive tough situations such as
      food shortage. However, the underlying molecular mechanism is not fully
      understood. Here, we provided evidence that the regulatory peptide prokineticin 2
      (PK2) played an important role in such an adaptation. The PK2 expression was
      rapidly induced in the hypothalamic paraventricular nucleus (PVN) after fasting,
      which can be mimicked by 2-deoxy-D-glucose (2-DG) injection. The fasting-induced
      arousal was absent in the PK2-deficient (PK2(-/-)) mice. Furthermore, PK2(-/-)
      mice showed less energy expenditure and body weight loss than wild-type (WT)
      controls upon fasting. As a result, PK2(-/-) mice entered torpor after fasting.
      Supply of limited food (equal to 5% of body weight) daily during fasting rescued
      the body weight loss and hypothermal phenotype in WT mice, but not in PK2(-/-)
      mice. Our study thus demonstrated PK2 as a regulator in the thermoregulation and
      energy expenditure.

PMID- 22960407
TI  - Analgesic properties of chimeric peptide based on morphiceptin and PFRTic-amide.
AB  - A chimeric opioid peptide (MCRT, YPFPFRTic-NH(2)) was here designed and
      synthesized. This peptide was based on morphiceptin (YPFP-NH(2)) and a
      neuropeptide FF (NPFF) derivative (PFRTic-NH(2)) sharing one proline. This
      peptide is intended to produce potent analgesia. MCRT was found to induce
      analgesic activity in a dose- and time-dependent manner, as indicated by a tail
      flick latency test in mice to which it had been intracerebroventricularly
      administered (5-60 min, 0.025-2.5 nmol/kg (0.5-50 pmol per mouse), ED(50)=1.49
      nmol/kg). At 2.5nmol/kg, MCRT showed significantly higher levels of analgesic
      activity than morphiceptin or PFR(Tic)amide at 2500 nmol/kg. Naltrindole and
      cyprodime were found to partially but significantly inhibit this analgesic
      activity, but naloxone blocked it completely. The kappa opioid receptor
      antagonist nor-BNI was found to slightly inhibit MCRT and morphiceptin. Pre
      injection of BIBP3226 and co-administration of NPFF and MCRT showed that NPFF
      receptors were involved in the analgesia of MCRT. BIBP3226 was found to weaken
      the analgesic effects of MCRT, but BIBP3226 could not block the analgesic effects
      of PFR(Tic)amide. Overall, MCRT was found to have stronger analgesic activity
      than morphiceptin or PFR(Tic)amide when interacting with mixed MU/delta opioid
      receptor interactions. MCRT also showed partial interaction with NPFF receptors.

PMID- 22960408
TI  - Connective tissue growth factor level is increased in patients with liver
      cirrhosis but is not associated with complications or extent of liver injury.
AB  - Connective tissue growth factor (CTGF) is a profibrotic protein whose systemic
      levels are increased in liver cirrhosis. Here, association of CTGF with stages of
      liver injury and complications of cirrhotic liver disease has been analyzed in
      patients with different aetiologies of hepatic injury. CTGF is significantly
      increased in portal venous serum (PVS), hepatic venous serum (HVS) and systemic
      venous serum (SVS) of 46 patients with liver cirrhosis compared to eight liver
      healthy controls. In patients' blood samples CTGF in HVS is about 6% higher than
      PVS levels indicating that CTGF produced in the liver is released to the
      circulation. CTGF is not associated with stages of liver cirrhosis defined by
      CHILD-PUGH or MELD score nor with secondary complications of portal hypertension
      (varices, ascites, spontaneous bacterial peritonitis). Transforming growth factor
      beta (TGFbeta) induces CTGF synthesis in hepatocytes and a positive association
      of systemic TGFbeta1 and SVS and HVS CTGF is found. Three months after placing
      transjugular intrahepatic portosystemic shunt (TIPS) hepatic venous pressure
      gradient is reduced whereas CHILD-PUGH score, TGFbeta1 and CTGF are not altered
      in serum of 15 patients. Current data show that the cirrhotic liver releases
      little CTGF but SVS, HVS and PVS CTGF levels are not associated with residual
      liver function and complications of cirrhosis.

PMID- 22960409
TI  - Effects of trypsin, thrombin and proteinase-activated receptors on guinea pig
      common bile duct motility.
AB  - Trypsin and thrombin activate proteinase-activated receptors (PARs), which
      modulate gastrointestinal motility. The common bile duct is exposed to many
      proteinases that can activate PARs, especially during infection and stone
      obstruction. We investigated PAR effects on common bile duct motility in vitro.
      Contraction and relaxation of isolated guinea pig common bile duct strips caused
      by PAR(1), PAR(2) and PAR(4) agonists were measured using isometric transducers.
      Reverse transcription polymerase chain reaction (RT-PCR) was performed to
      determine the expression of PAR(1) and PAR(2). Thrombin and two PAR(1) peptide
      agonists, TFLLR-NH(2) and SFLLRN-NH(2), evoked moderate relaxation of the
      carbachol-contracted common bile duct in a concentration-dependent manner.
      Trypsin and three PAR(2) peptide agonists, 2-furoyl-LIGRLO-NH(2), SLIGKV-NH(2)
      and SLIGRL-NH(2), generated moderate to marked relaxation as well. The existence
      of PAR(1) and PAR(2) mRNA in the common bile duct was identified by RT-PCR.
      Moreover, two PAR(4)-selective agonists, AYPGKF-NH(2) and GYPGQV-NH(2), produced
      relaxation of the common bile duct. In contrast, all PAR(1), PAR(2) and PAR(4)
      inactive control peptides did not elicit relaxation. This indicates that PAR(1),
      PAR(2) and PAR(4) mediate common bile duct relaxation. The thrombin, TFLLR-NH(2),
      trypsin, and AYPGKF-NH(2)-induced responses were not affected by tetrodotoxin,
      implying that the PAR effects are not neurally mediated. Our findings provide the
      first evidence that PAR(1) and PAR(2) mediate whereas agonists of PAR(4) elicit
      relaxation of the guinea pig common bile duct. Trypsin and thrombin relax the
      common bile duct. PARs may play an important role in the control of common bile
      duct motility.

PMID- 22960410
TI  - An inhibitor of leukotriene synthesis affects vasopressin secretion following
      osmotic stimulus in rats.
AB  - Previous studies revealed the presence of LTC(4) synthase in paraventricular
      vasopressinergic neurons, suggesting a role for leukotrienes (LTs) in certain
      neuroendocrine system functions. Our aim was to study the effect of an inhibitor
      of LT synthesis in the release of arginine vasopressin (AVP) following an osmotic
      stimulus in rats. Male Wistar rats received an intra-cerebroventricular injection
      of 2 MUl of the LT synthesis inhibitor MK-886 (1, 2, or 4 MUg/kg), or vehicle
      (DMSO 5%), 1h before an intraperitoneal injection of hypertonic saline (NaCl 2M)
      or isotonic saline (NaCl 0.01 M) in a volume corresponding to 1% of body weight.
      Thirty minutes after the osmotic stimulus, the animals were decapitated and blood
      was collected for determining hematocrit, plasma osmolality and plasma AVP
      levels. As expected, the injection of hypertonic saline significantly increased
      (P<0.05) the hematocrit, plasma osmolality and plasma AVP levels. While
      inhibiting LT synthesis by central administration of MK-886 did not cause any
      additional increase in hematocrit or osmolality, plasma AVP levels were augmented
      (P<0.05). We conclude that central leukotrienes may have a modulatory role in AVP
      secretion following an osmotic stimulus, this deserving future studies.

PMID- 22960411
TI  - Physiologically based quantitative modeling of unihemispheric sleep.
AB  - Unihemispheric sleep has been observed in numerous species, including birds and
      aquatic mammals. While knowledge of its functional role has been improved in
      recent years, the physiological mechanisms that generate this behavior remain
      poorly understood. Here, unihemispheric sleep is simulated using a
      physiologically based quantitative model of the mammalian ascending arousal
      system. The model includes mutual inhibition between wake-promoting monoaminergic
      nuclei (MA) and sleep-promoting ventrolateral preoptic nuclei (VLPO), driven by
      circadian and homeostatic drives as well as cholinergic and orexinergic input to
      MA. The model is extended here to incorporate two distinct hemispheres and their
      interconnections. It is postulated that inhibitory connections between VLPO
      nuclei in opposite hemispheres are responsible for unihemispheric sleep, and it
      is shown that contralateral inhibitory connections promote unihemispheric sleep
      while ipsilateral inhibitory connections promote bihemispheric sleep. The
      frequency of alternating unihemispheric sleep bouts is chiefly determined by
      sleep homeostasis and its corresponding time constant. It is shown that the model
      reproduces dolphin sleep, and that the sleep regimes of humans, cetaceans, and
      fur seals, the latter both terrestrially and in a marine environment, require
      only modest changes in contralateral connection strength and homeostatic time
      constant. It is further demonstrated that fur seals can potentially switch
      between their terrestrial bihemispheric and aquatic unihemispheric sleep patterns
      by varying just the contralateral connection strength. These results provide
      experimentally testable predictions regarding the differences between species
      that sleep bihemispherically and unihemispherically.

PMID- 22960412
TI  - High 18F-fluorothymidine uptake for invasive thymoma.
AB  - We report an invasive thymoma discovered incidentally by an 18F-FLT
      (fluorothymidine) PET study on a 48-year-old woman. The patient had equivocal
      breast lesions in her bilateral breasts. She entered a clinical 18F-FLT PET trial
      in our hospital to differentiate malignant breast tumors from benign ones. No 18F
      FLT-avid lesions in her breasts were revealed. But an intense 18F-FLT uptake
      lesion was noted in her right anterior mediastinum. However, an F-FDG PET scan
      showed only mild F-FDG uptake in the lesion. Video-assisted thoracic surgery
      thymectomy was subsequently performed, and the final pathology showed invasive
      thymoma.

PMID- 22960415
TI  - Attentional orienting to mnemonic representations: reduction of load-sensitive
      maintenance-related activity in the intraparietal sulcus.
AB  - The orienting of attention to internal or mnemonic representations held in visual
      working memory (VWM) has recently become a field of increasing interest. While a
      number of studies support the hypothesis that attention to selected
      representations in VWM reduces memory load, conclusive findings are still
      missing. In this event-related functional magnetic resonance imaging (fMRI)
      study, we directly investigated whether attentional orienting to mnemonic
      representations reduces activity in VWM storage-related areas of the brain. VWM
      load was manipulated by asking subjects to memorize two, four or six items. A
      retro-cue during the subsequent delay period asked subjects to attend to just one
      of these items for a subsequent test. This was compared to trials where subjects
      were required to continue attending to all items for the subsequent test. Data
      show reduction of load-sensitive maintenance-related activity along the right
      intraparietal sulcus (IPS), directly linked to attentional orienting. While
      activity in the anterior IPS reflected the number of representations in the focus
      of attention, the activation pattern in the posterior IPS suggested residual
      activation related to unattended items. This dissociation is in line with a
      functional subdivision of the right IPS according to attentional and mnemonic
      properties.

PMID- 22960413
TI  - The acute and regulatory phases of time-course changes in gill mitochondrion-rich
      cells of seawater-acclimated medaka (Oryzias dancena) when exposed to hypoosmotic
      environments.
AB  - The recent model showed that seawater (SW) mitochondrion-rich (MR) cells with
      hole-type apical openings secrete Cl(-) through the transporters including the
      Na(+), K(+)-ATPase (NKA), Na(+), K(+), 2Cl(-) cotransporter (NKCC), and cystic
      fibrosis transmembrane conductance regulator (CFTR). The present study focused on
      the dynamic elimination of the Cl(-) secretory capacity and illustrated different
      phases (i.e., acute and regulatory phases) of branchial MR cells in response to
      hypoosmotic challenge. Time-course remodeling of the cell surfaces and the
      altered expressions of typical ion transporters were observed in the branchial MR
      cells of SW-acclimated brackish medaka (Oryzias dancena) when exposed to fresh
      water (FW). On the 1st day post-transfer, rapid changes were shown in the acute
      phase: the flat-type MR cells with large apical surfaces replaced the hole-type
      cells, the gene expression of both Odnkcc1a and Odcftr decreased, and the apical
      immunostaining signals of CFTR protein disappeared. The basolateral
      immunostaining signals of NKCC1a protein decreased throughout the regulatory
      phase (>1day post-transfer). During this period, the size and number of NKA
      immunoreactive MR cells were significantly reduced and elevated, respectively.
      Branchial NKA expression and activity were maintained at constant levels in both
      phases. The results revealed that when SW-acclimated brackish medaka were
      transferred to hypoosmotic FW for 24h, the Cl(-) secretory capacity of MR cells
      was eliminated, whereas NKCC1a protein was retained to maintain the
      hypoosmoregulatory endurance of the gills. The time-course acute and regulatory
      phases of gill MR cells showed different strategies of the euryhaline medaka when
      subjected to hypoosmotic environments.

PMID- 22960417
TI  - International classification of disease clinical modification 9 modeling of a
      patient comorbidity score predicts incidence of perioperative complications in a
      nationwide inpatient sample assessment of complications in spine surgery.
AB  - OF BACKGROUND DATA: A patient comorbidity score (RCS) was developed from a
      prospective study of complications occurring in spine surgery patients.
      OBJECTIVE: To validate the RCS, we present an International Classification of
      Disease Clinical Modification (ICD-CM)-9 model of the score and correlate the
      score with complication incidence in a group of patients from the Nationwide
      Inpatient Sample database. We compare the predictive value of the score with the
      Charlson index. STUDY DESIGN: We conducted a retrospective assessment of
      Nationwide Inpatient Sample patients undergoing cervical or thoracolumbar spine
      surgery for degenerative pathology from 2002 to 2009. METHODS: We generated an
      ICD-9-CM coding-based model of our prospectively derived RCS, categorizing
      diagnostic codes to represent relevant comorbidities. Multivariate models were
      constructed to eliminate the least significant variables. ICD-9-CM coding was
      also used to calculate a Charlson comorbidity score for each patient. The
      accuracy of the RCS was compared with the Charlson index through the use of a
      receiver-operating curve. RESULTS: A total of 352,535 patients undergoing 369,454
      spine procedures for degenerative disease were gathered. Hypertension and
      hyperlipidemia were the most common comorbidities. Cervical procedures resulted
      in 8286 complications (4.50%), whereas thoracolumbar procedures produced 25,118
      complications (13.55%). Increasing RCS correlated linearly with increasing
      complication incidence (odds ratio [OR] 1.11; 95% confidence interval [CI], 1.10
      1.13; P<0.0001). Logistic regression revealed that neurological deficit, cardiac
      conditions, and drug or alcohol use had greatest association with complication
      occurrence. The Charlson index also correlated with complication occurrence in
      both cervical (OR 1.25; 95% CI, 1.23-1.27) and thoracolumbar (OR 1.11; 95% CI,
      1.10-1.12) patient groups. Receiver-operating curve analysis allowed a comparison
      of accuracy of the indices by comparing predictive values. The RCS performed as
      well as the Charlson index in predicting complication occurrence in both cervical
      and thoracic spine patients. CONCLUSIONS: ICD-9-based modeling validated that RCS
      correlates with complication occurrence. The RCS performed as well as the
      Charlson index in predicting risk of complication in spine patients.

PMID- 22960418
TI  - Novel motion preservation device for atlantoaxial instability.
AB  - STUDY DESIGN: An in vitro cadaveric biomechanical study. OBJECTIVE: To evaluate
      the anteroposterior (A-P) stability and the flexibility of our novel motion
      preservation device (MPD) using cadaveric cervical spines. SUMMARY OF BACKGROUND
      DATA: The MPD intended to restrict the A-P instability of the C1-C2 complex and
      to preserve the axial rotation, flexion, extension, and lateral bending was
      designed and produced. The stability and the flexibility of the MPD was
      evaluated. METHODS: Ten embalmed cadaveric specimens were loaded with pure A-P
      translation force and the A-P translational distances were measured. Each
      specimen was tested for the following 4 models, respectively: Intact (control),
      the Dens-removed, the MPD instrumented, and a Rod fixation system instrumented.
      Fifteen specimens were loaded with pure moments (up to 1.5 Nm), and the C1-C2
      range of motion (ROM) was measured for flexion, extension, lateral bending, and
      axial rotation using a stereophotogrammetry motion analysis system. RESULTS: Mean
      A-P translational distances were 4.26 mm in Intact, 13.1 in the Dens-removed,
      5.42 in the MPD, and 2.58 in the Rod fixation. The distance values with the MPD
      had no significant difference compared with Intact. Mean C1-C2 ROM of Intact, the
      MPD, and the Rod fixation at 1.5 Nm were: 14.7, 6.96, and 2.11 degrees in
      flexion, 6.46, 4.72, and 2.84 degrees in extension, 3.29, 4.02, and 1.01 degrees
      in right lateral bending, 4.92, 4.58, and 1.84 degrees in left lateral bending,
      26.4, 15.4, and 1.16 degrees in right axial rotation, and 25.6, 14.3, and 1.21
      degrees in left axial rotation, respectively. CONCLUSIONS: The MPD restricted the
      A-P instability of the C1-C2 complex. In flexion, extension, and axial rotation,
      the C1-C2 ROM of the MPD was about 50% of the ROM in Intact, whereas equivalent
      to Intact in lateral bending.

PMID- 22960416
TI  - White matter fiber compromise contributes differentially to attention and emotion
      processing impairment in alcoholism, HIV-infection, and their comorbidity.
AB  - Alcoholism (ALC) and HIV-1 infection (HIV) each affects emotional and attentional
      processes and integrity of brain white matter fibers likely contributing to
      functional compromise. The highly prevalent ALC+HIV comorbidity may exacerbate
      compromise. We used diffusion tensor imaging (DTI) and an emotional Stroop Match
      to-Sample task in 19 ALC, 16 HIV, 15 ALC+HIV, and 15 control participants to
      investigate whether disruption of fiber system integrity accounts for compromised
      attentional and emotional processing. The task required matching a cue color to
      that of an emotional word with faces appearing between the color cue and the
      Stroop word in half of the trials. Nonmatched cue-word color pairs assessed
      selective attention, and face-word pairs assessed emotion. Relative to controls,
      DTI-based fiber tracking revealed lower inferior longitudinal fasciculus (ilf)
      integrity in HIV and ALC+HIV and lower uncinate fasciculus (uf) integrity in all
      three patient groups. Controls exhibited Stroop effects to positive face-word
      emotion, and greater interference was related to greater callosal, cingulum and
      ilf integrity. By contrast, HIV showed greater interference from negative Stroop
      words during color-nonmatch trials, correlating with greater uf compromise. For
      face trials, ALC and ALC+HIV showed greater Stroop-word interference, correlating
      with lower cingulate and callosal integrity. Thus, in HIV, conflict resolution
      was diminished when challenging conditions usurped resources needed to manage
      interference from negative emotion and to disengage attention from wrongly cued
      colors (nonmatch). In ALC and ALC+HIV, poorer callosal integrity was related to
      enhanced emotional interference suggesting curtailed interhemispheric exchange
      needed between preferentially right-hemispheric emotion and left-hemispheric
      Stroop-word functions.

PMID- 22960419
TI  - Intraoperative Neural Mobility and Postoperative Neurological Recovery in
      Anterior Cervical Decompression Surgery: Evaluation With Intraoperative
      Sonography.
AB  - STUDY DESIGN: A study using intraoperative sonography (IOS) was conducted for
      evaluating neural mobility in anterior cervical decompression surgery.
      OBJECTIVES: To analyze decompression status and mobility of the spinal cord and
      the nerve root during anterior cervical decompression and to clarify its
      relevance to the postoperative neurological recovery. SUMMARY OF BACKGROUND DATA:
      Several papers introduced the usefulness of IOS assessments; however, there have
      been no reports systematically evaluating the neural mobility in anterior
      cervical decompression surgery. METHODS: Eighty-four consecutive patients with
      compressive myelopathy who underwent anterior cervical decompression procedures
      were studied. The decompression status of the spinal cord was evaluated with IOS
      and classified into 3 grades according to the restoration pattern of the space
      ventral to the cord. Pulsatile motion of the spinal cord in cranio-caudal
      direction was named "sliding pulsation" and graded into 3 groups. The nerve root
      pulsation was also assessed using the IOS short-axis views. This study analyzed
      whether those neural mobility in anterior cervical decompression surgery had
      relevance to postoperative neurological recovery, which was assessed by the Japan
      Orthopaedic Association score. RESULTS: The mean recovery rate of the Japan
      Orthopaedic Association score was 59.1% in total. According to the decompression
      status in IOS, 67 patients who acquired space ventral to the spinal cord
      indicated 64.3% of the recovery rate which was significantly higher than 36.6% of
      the other patients on an average. As to the sliding pulsation of the cord, 10
      patients who failed to show this particular motion indicated significantly lower
      recovery rate as 36.9%. In addition, 6 patients who did not exhibit nerve root
      pulsation indicated just 29.3% of recovery rate, and 4 of them failed to show the
      cord sliding motion. CONCLUSIONS: Sonographic evaluation during anterior cervical
      decompression surgery provided very useful information of neural decompression
      status that had significant correlation with postoperative neurological recovery.

PMID- 22960420
TI  - Surgical Management of Spinal Synovial Cysts: A Series of 23 Patients and
      Systematic Analysis of the Literature.
AB  - STUDY DESIGN: Retrospective cohort and review of the literature. OBJECTIVE: To
      compare surgical strategies for the management of spinal synovial cysts. SUMMARY
      OF BACKGROUND DATA: The recent multiplication of retrospective series of patients
      with spinal synovial cysts has led to a reappraisal of their incidence and
      clinical significance. Although surgery is considered the treatment of choice,
      there is still no agreement over which surgical technique should be used.
      METHODS: We retrospectively reviewed 23 consecutive patients undergoing surgery
      for a spinal synovial cyst in our department between 2004 and 2010. Surgical
      procedures were classified into the following 4 categories: cystectomy by an
      interlaminar approach, hemilaminectomy, laminectomy, or associated with
      instrumented spinal fusion. Clinical outcome, cyst recurrence, need for
      subsequent fusion, and perioperative complications were compared between these
      groups. RESULTS: Of the patients included in the present cohort, 11 underwent
      cyst excision by an interlaminar approach, 8 had a hemilaminectomy, 2 had a
      laminectomy, and 2 underwent instrumented fusion. "Excellent" or "good" clinical
      outcome on the Macnab modified scale were achieved for 16 patients (69.6%), and
      there were 2 perioperative complications, 2 cyst recurrences, and 1 secondary
      fusion. Of the 519 patients reported in the literature, overall clinical outcome
      was either "excellent" or "good" for 83% of all patients. However, unfavorable
      outcome was more likely in patients treated with decompression alone (80/396)
      than decompression with fusion (10/123) (20.2% vs. 8.1%; P=0.003) and cyst
      recurrence (13/396 vs. 0/123; P=0.028). In contrast, the rate of perioperative
      complications was significantly higher in the fusion group (23/123) compared with
      decompression alone (11/396) (18.7% vs. 2.8%; P<0.0001). CONCLUSIONS: In patients
      with spinal synovial cyst, spinal fusion seems to decrease the risk of
      unfavorable clinical outcome and cyst recurrence and associated with a
      considerably higher rate of perioperative complications.

PMID- 22960422
TI  - Efficacy of serum samples stored on filter paper for the detection of antibody to
      Leptospira spp. by microagglutination test (MAT).
AB  - The aim of this study was to investigate the microagglutination test (MAT)
      results in serum samples dried on filter paper and stored at different
      temperatures during 1day, 7days, 30days and 1year to determine the stability of
      sera antibody against leptospires. Serum samples collected onto filter paper for
      the detection of leptospires antibody was compared with MAT in a study of 300
      serum samples from patients with suspected leptospirosis. Among 300 fresh serum
      samples analyzed by MAT 156 (52%) were positive and 144 (48%) negative. All the
      negative fresh serum samples were negative when dried on filter paper
      (specificity 100%). The sensitivity of MAT performed on dried serum samples was
      100%. Storage on filter paper at room temperature and at 4 degrees C for 1 and
      7days did not affect the MAT titers. For up to 7days, 98.72% of dried serum
      samples had titers identical to those of the corresponding serum samples, and
      1.18% of dried serum samples showed 1 dilution of difference. After a storage
      period of one month a prozone phenomenon was observed. After a storage period of
      one year all serum samples were negative. Serum samples collected onto filter
      paper are a convenient source of antibodies for serological diagnosis and
      epidemiological surveys.

PMID- 22960421
TI  - Perinatal exposure to 50 ppb sodium arsenate induces hypothalamic-pituitary
      adrenal axis dysregulation in male C57BL/6 mice.
AB  - Over the past two decades, key advancements have been made in understanding the
      complex pathology that occurs following not only high levels of arsenic exposure
      (>1 ppm) but also levels previously considered to be low (<100 ppb). Past studies
      have characterized the deleterious effects of arsenic on the various functions of
      cardiovascular, pulmonary, immunological, respiratory, endocrine and neurological
      systems. Other research has demonstrated an elevated risk of a multitude of
      cancers and increased rates of psychopathology, even at very low levels of
      arsenic exposure. The hypothalamic-pituitary-adrenal (HPA) axis represents a
      multisite integration center that regulates a wide scope of biological and
      physiological processes: breakdown within this system can generate an array of
      far-reaching effects, making it an intriguing candidate for arsenic-mediated
      damage. Using a mouse model, we examined the effects of perinatal exposure to 50
      ppb sodium arsenate on the functioning of the HPA axis through the assessment of
      corticotrophin-releasing factor (CRF), proopiomelanocortin (Pomc) mRNA,
      adrenocorticotrophin hormone (ACTH), corticosterone (CORT), 11beta-hydroxysteroid
      dehydrogenase Type 1 (11beta-HSD 1), and glucocorticoid receptor (GR) protein and
      mRNA. Compared to controls, we observed that the perinatal arsenic-exposed
      offspring exhibit an increase in hypothalamic CRF, altered CORT secretion both at
      baseline and in response to a stressor, decreased hippocampal 11beta-HSD 1 and
      altered subcellular GR distribution in the hypothalamus. These data indicate
      significant HPA axis impairment at post-natal day 35 resulting from perinatal
      exposure to 50 ppb sodium arsenate. Our findings suggest that the dysregulation
      of this critical regulatory axis could underlie important molecular and cognitive
      pathology observed following exposure to arsenic.

PMID- 22960423
TI  - Development and evaluation of a real-time reverse transcription-loop-mediated
      isothermal amplification assay for rapid serotyping of foot-and-mouth disease
      virus.
AB  - A one-step, real-time reverse transcription-loop-mediated isothermal
      amplification assay (RT-LAMP) for rapid detection and serotyping of Indian foot
      and-mouth disease virus (FMDV) is described. The RT-LAMP assay was found to be
      10(3)-10(5) fold more sensitive in comparison with RT-PCR, with a detection limit
      ranging from 10(-3) to 10(-5) TCID(50) of virus samples of all three serotypes.
      The RT-LAMP assay and qRT-PCR could detect 100 percent of clinical samples of
      three serotypes, whereas the RT-PCR detected 69.7% of type O, 58.1% of type A and
      60.0% of Asia 1 samples. The qRT-PCR has the same sensitivity as the RT-LAMP. The
      assay conditions with absence of cross reactivity within the three serotypes of
      FMDV and FMDV negative samples were established. The RT-LAMP assay could detect
      100% of samples stored in FTA((r)) cards. In comparison with the performance of
      the RT-PCR; the RT-LAMP appears to be more sensitive, rapid and specific, with
      the potential for use as a point-of-care (POC) test, especially in developing
      countries. The use of FTA((r)) cards for the preservation of RNA samples coupled
      with the RT-LAMP assay for the identification of serotypes may help in achieving
      improved FMDV serotype identification both in the field and in the laboratory.

PMID- 22960424
TI  - Mitigation of endometriosis using regenerative cerium oxide nanoparticles.
AB  - Cerium oxide nanoparticles (nanoceria) have recently received attention from the
      scientific community due to their unique free radicals (specially superoxide
      radical and hydrogen peroxide) scavenging property in biological system, both in
      vitro and in vivo. It is suggested that free radicals play an important role in
      the pathogenesis of endometriosis. In this study we have shown that nanoceria
      mitigate the endometrial lesions induced in mice model by decreasing oxidative
      stress and inhibiting angiogenesis. Moreover, nanoceria were also observed to
      protect endometriosis-related adverse effects on the oocytes, which is critical
      for successful pregnancy. Summarizing, nanoceria have shown promising efficacy
      against endometriosis related pathogenesis. FROM THE CLINICAL EDITOR: Free
      radicals have been implemented in the pathogenesis of endometriosis. In a murine
      model the authors demonstrated successful treatment of endometriosis with
      nanoceria, and protection of endometriosis-related adverse effects on the
      oocytes, paving the way to potential clinical translational applications in the
      future.

PMID- 22960425
TI  - Biodistribution and biopersistence of ceria engineered nanomaterials: size
      dependence.
AB  - The aims were to determine the biodistribution, translocation, and persistence of
      nanoceria in the brain and selected peripheral organs. Nanoceria is being studied
      as an anti-oxidant therapeutic. Five, 15, 30, or 55 nm ceria was iv infused into
      rats which were terminated 1, 20, or 720 h later. Cerium was determined in blood,
      brain, liver, and spleen. Liver and spleen contained a large percentage of the
      dose, from which there was no significant clearance over 720 h, associated with
      adverse changes. Very little nanoceria entered brain parenchyma. The results
      suggest brain delivery of nanoceria will be a challenge. FROM THE CLINICAL
      EDITOR: This team of investigators revealed that nanoceria, which is being
      studied as an anti-oxidant, has very limited uptake by the brain regardless of
      the range of sizes studied, suggesting major challenges in the application of
      this novel approach in the central nervous system.

PMID- 22960426
TI  - TGFbeta overrides HNF4alpha tumor suppressing activity through GSK3beta
      inactivation: implication for hepatocellular carcinoma gene therapy.
AB  - BACKGROUND & AIMS: The tumor fate derives from cell autonomous properties and
      niche microenvironmental cues. The transforming growth factor beta (TGFbeta) is a
      major microenvironmental factor for hepatocellular carcinoma (HCC) influencing
      tumor dedifferentiation, induction of epithelial-to-mesenchymal transition (EMT)
      and acquisition of metastatic properties. The loss of the transcriptional factor
      HNF4alpha is a predominant mechanism through which HCCs progress to a more
      aggressive phenotype; its re-expression, reducing tumor formation and repressing
      EMT program, has been suggested as a therapeutic tool for HCC gene therapy. We
      investigated the influence of TGFbeta on the anti-EMT and tumor suppressor
      HNF4alpha activity. METHODS: Cell motility and invasion were analyzed by wound
      healing and invasion assays. EMT was evaluated by RT-qPCR and immunofluorescence.
      ChIP and EMSA assays were utilized for investigation of the HNF4alpha DNA binding
      activity. HNF4alpha post-translational modifications (PTMs) were assessed by 2-DE
      analysis. GSK3beta activity was modulated by chemical inhibition and constitutive
      active mutant expression. RESULTS: We demonstrated that the presence of TGFbeta
      impairs the efficiency of HNF4alpha as tumor suppressor. We found that TGFbeta
      induces HNF4alpha PTMs that correlate with the early loss of HNF4alpha DNA
      binding activity on target gene promoters. Furthermore, we identified the
      GSK3beta kinase as one of the TGFbeta targets mediating HNF4alpha functional
      inactivation: GSK3beta chemical inhibition results in HNF4alpha DNA binding
      impairment while a constitutively active GSK3beta mutant impairs the TGFbeta
      induced inhibitory effect on HNF4alpha tumor suppressor activity. CONCLUSIONS:
      Our data identify in the dominance of TGFbeta a limit for the HNF4alpha-mediated
      gene therapy of HCC.

PMID- 22960427
TI  - All-cause and liver-related mortality in hepatitis C infected drug users followed
      for 33 years: a controlled study.
AB  - BACKGROUND & AIMS: The course of chronic hepatitis C virus (HCV) in injecting
      drug users (IDUs) has not been well described. The aim of this study was to
      compare long-term all-cause and liver-related mortality among anti-HCV positive
      IDUs with and without persisting HCV infection. METHODS: A retrospective
      prospective controlled cohort design was applied. All IDUs admitted to resident
      drug treatment (1970-1984) and with available stored sera were screened for anti
      HCV antibody. Anti-HCV positive individuals were further tested for the presence
      of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA
      positive (n=328) and HCV RNA negative individuals (n=195). The observation was
      accomplished through register linkage to national registers. Mean observation
      time was 33 years. RESULTS: All-cause mortality rate was 1.85 (95% CI 1.62-2.11)
      per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07
      1.79). Mortality rates were not influenced by persisting HCV infection. Main
      causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%).
      Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive
      subjects. Five of 13 deaths among male IDUs with persisting HCV infection
      occurring after the age of 50 years were caused by liver disease. CONCLUSIONS:
      The all-cause mortality in IDUs is high and with no difference between HCV RNA
      positive and HCV RNA negative individuals, the first three decades after HCV
      transmission. However, among IDUs with chronic HCV infection who have survived
      until 50years of age, HCV infection emerges as the main cause of death.

PMID- 22960428
TI  - Effect of peptides and their introduction methods on target gene transfer of gene
      vector based on disulfide-containing polyethyleneimine.
AB  - To evaluate the effect of different peptides as well as their introduction
      methods on target gene transfer of gene vectors based on disulfide-containing
      polyethyleneimine (SS-PEI), a series of peptides including N(3)-GRGDSF, GRGDSF,
      and EEEEEEEEGRGDSF (E(8)GRGDSF) were prepared. N(3)-GRGDSF was conjugated to SS
      PEI by click chemistry and SS-PEI-GRGDSF was obtained. GRGDSF was non-covalently
      introduced into SS-PEI/DNA mainly through hydrogen bonding to obtain SS
      PEI/DNA/GRGDSF complexes, whereas E(8)GRGDSF was further non-covalently
      introduced to SS-PEI/DNA through electrostatic force to obtain SS
      PEI/DNA/E(8)GRGDSF complexes. Transfection efficiency of all complexes with
      peptides was lower than that of SS-PEI/DNA in COS-7 cells due to the fact that
      nonspecific endocytosis was prohibited after peptide introduction. Whereas in
      HeLa cells, transfection activity of SS-PEI-GRGDSF/DNA and SS-PEI/DNA/E(8)GRGDSF
      at certain w/w ratios was higher than that of SS-PEI/DNA. But the transfection
      efficiency of SS-PEI/DNA/E(8)GRGDSF at peptide/DNA w/w ratios higher than 30
      dropped due to targeted binding interactions between surplus E(8)GRGDSF and the
      integrins in HeLa cells, which would prohibit specific endocytosis of E(8)GRGDSF
      in complexes. Transfection activity of SS-PEI/DNA/GRGDSF was lower than or
      comparable to that of SS-PEI/DNA because of loose complexes constructed by
      hydrogen bonding between GRGDSF and SS-PEI/DNA.

PMID- 22960429
TI  - Hyperphosphorylation of intermediate filament proteins is involved in microcystin
      LR-induced toxicity in HL7702 cells.
AB  - Microcystin-LR (MC-LR) is commonly characterized as a hepatotoxin, which can
      cause disruption of keratin filaments. Keratins, however, account for only two
      types of intermediate filaments (IFs), and the potential involvement of other IF
      proteins in MC-LR-induced toxicity and the underlying mechanisms are still
      unclear. In this study, the human normal liver cell line HL7702 was used to
      investigate whether MC-LR can change the transcription, translation, and
      phosphorylation levels of major IF proteins and to elucidate the underlying
      mechanisms. The results showed that MC-LR triggered an accumulation of IFs around
      the nucleus and led to the formation of dense bundles. When the cells were
      treated with 10MUM MC-LR, cell proliferation significantly decreased with an
      increase in apoptosis and cell cycle arrest. Moreover, the mRNA and protein
      levels of keratin 18, vimentin and lamin A/C were not changed; however, the
      phosphorylation of K8/18 and vimentin was significantly increased. Furthermore,
      we found MC-LR exposure caused phosphoactivation of P38, JNK and ERK1/2 in a
      concentration-dependent manner, and P38 and ERK1/2 were involved in MC-LR-induced
      hyperphosphorylation of IF proteins. Taken together, the results of this study
      suggest that MC-LR exerts its potential hepatotoxicity through MAPK pathway
      activation, which cause hyperphosphorylation of IF proteins and result in
      cytoskeletal architecture remodeling and cell survival/death regulation. Since
      IFs serve as signaling platforms and dozens of IF proteins are involved in
      different signaling pathways, future studies focus on different IFs may provide
      helpful insights into the mechanisms of MC-LR toxicity.

PMID- 22960431
TI  - The distribution of the prostaglandin E receptor type 2 (EP2) in the detrusor of
      the guinea pig.
AB  - OBJECTIVE: To explore the distribution of prostaglandin E receptor type 2 (EP2)
      in the bladder muscle layers and its spatial relationship to cyclo-oxygenase type
      1 (COX I). MATERIALS AND METHODS: Twelve male guinea pigs were killed by cervical
      dislocation, the bladders removed and fixed in 4% paraformaldehyde in PBS. Frozen
      sections of 10 MUm were cut and stained with antibodies to EP2, COX I and
      vimentin. RESULTS: EP2 receptor immunoreactivity is located on the smooth muscle
      cells as well as on vimentin positive surface muscle and intramuscular
      interstitial cells. EP2 expression on interstitial cells is highly localized.
      Discrete regions of intense staining were observed on the interstitial cell
      processes. COX I is expressed in the muscle interstitial cells and was found to
      be located on discrete regions of the cell and cell processes. Double staining
      with EP2 and COX I suggests that the regions of a cell expressing EP2 are
      different from those expressing COX I. CONCLUSIONS: The presence of COX I,
      prostaglandin E receptor type 2 (EP2) immune-reactivity in the network of
      interstitial cells suggests a role of this network in the propagation of signals.
      Due to a cAMP coupling of the EP2 receptor in many other tissues and a lower
      dissociation constant of EP2, it is suggested that a rise in PG levels may
      gradually push the balance from a relaxant EP2 effect towards a contractile
      effect. Hence, PG could have a modulatory role on the non-voiding bladder
      contractions by changing the threshold level for excitability of the interstitial
      cell network.

PMID- 22960430
TI  - Eicosanoid profiling in colon cancer: emergence of a pattern.
AB  - Oxidative metabolism of polyunsaturated fatty acids has been linked to
      tumorigenesis in general and colonic tumorigenesis in particular. Earlier studies
      showed that cyclooxygenase-2 (COX-2) and 15-lipoxygenase-1 (15-LOX-1) have
      opposing impacts on colonic tumorigenesis: COX-2 promotes while 15-LOX-1 inhibits
      colonic tumorigenesis. Advances in liquid chromatography/mass spectrometry have
      allowed for measurement of various products of oxidative metabolism in a single
      colonic biopsy specimen. Studies of LOX products in preclinical models and in
      patients with familial adenomatous polyposis and sporadic colorectal
      tumorigenesis indicate that LOX pathways are shifted during colonic tumorigenesis
      and that the main shift is downregulation of 15-LOX-1. This shift occurs during
      the polyp formation stage and thus offers the opportunity to modulate
      tumorigenesis early by correcting 15-LOX-1 downregulation. 

PMID- 22960432
TI  - Does using an asthma prompting form improve asthma care in a pediatric office?
AB  - An asthma exacerbation can be a life-threatening experience. This project tested
      the effectiveness of using a prompting form to improve childhood asthma care.
      Thirty randomly selected charts without a prompt form in a pediatric practice
      were compared for differences with thirty randomly selected charts with a
      completed prompting form. The number of medications reviewed (p=.001) and the
      frequency of refills written (p=.024) were significantly higher in the prompt
      group. Education was higher (p=.000) and triggers were more frequently discussed
      in the prompt group. The use of a prompting form facilitates discussion and
      improves preventive asthma care.

PMID- 22960433
TI  - Brief report: Creating a culture of evidence-based practice and nursing research
      in a pediatric hospital.
AB  - Evidence-based practice and nursing research are fundamental to the profession of
      nursing. However, enculturating these processes into daily nursing practice
      presents challenges. In an effort to identify these challenges specific to our
      organization's nursing division, the Barriers to Nursing Research survey was
      distributed to staff nurses (n=239) to assess barriers in utilizing evidence
      based practice and research in their daily practice. Based on these findings, our
      Evidence-Based Practice/Research Council developed a dissemination plan to be
      implemented over a 1 year time period that provided staff resources to implement
      evidence-based practice and nursing research. Upon completion of the year long
      implementation period, the same Barriers to Nursing Research survey was
      redistributed to staff (n=157). Pre and post survey results were compared for
      significance. Outcomes included an increase in projects, nurse driven research,
      and national presentations and publications.

PMID- 22960434
TI  - Impact of armodafinil on cognition in multiple sclerosis: a randomized, double
      blind crossover pilot study.
AB  - OBJECTIVE: Examine the efficacy of armodafinil in improving cognition in patients
      with multiple sclerosis (MS). BACKGROUND: Many patients with MS experience
      cognitive difficulties. Armodafinil has shown promise as a cognitive enhancer in
      other patient populations. No studies have examined whether armodafinil improves
      cognition in patients with MS. METHODS: We conducted a double-blind, placebo
      controlled, crossover study testing the efficacy of armodafinil in reducing
      cognitive problems in patients with MS. We randomized 17 patients to receive a
      dose of lactose placebo about 2 hours before they underwent a neuropsychological
      testing session. After a week-long washout period, we gave them a single 250-mg
      dose of armodafinil about 2 hours before testing them a second time. We
      randomized another 16 patients to receive the active drug first, then the
      placebo. We excluded 3 of the participants before analyzing the data. RESULTS:
      After correcting for multiple comparisons of the 8 neuropsychological dependent
      measures, we found that the patients had significantly improved delayed memory on
      a list-learning task after they took armodafinil (P = 0.0005), but no improvement
      on measures of executive function, visual memory, processing speed, or self
      reported fatigue. CONCLUSIONS: Results provide preliminary evidence that
      armodafinil may improve delayed verbal recall in patients with MS. A larger trial
      showing enhanced memory among patients taking long-term armodafinil could serve
      as a foundation for its possible clinical use as a memory enhancer in patients
      with MS.

PMID- 22960435
TI  - Motor symptoms at onset of Parkinson disease and risk for cognitive impairment
      and depression.
AB  - OBJECTIVE: To determine whether side and type of initial motor symptoms in
      Parkinson disease (PD) predict risk for later development of cognitive impairment
      or depressive symptoms. METHODS: We recruited 124 non-demented patients with PD
      to participate in a cohort study of cognitive function and depressive symptoms
      that used validated neuropsychological tests and a depressive symptom inventory.
      We first reviewed the patients' charts to determine their initial motor symptom
      and side of onset, and then classified the patients into 4 groups: right-sided
      onset tremor, right-sided onset bradykinesia/rigidity, left-sided onset tremor,
      and left-sided onset bradykinesia/rigidity. We excluded patients with bilateral
      symptom onset. We used analysis of variance on neuropsychological test
      performance and depressive symptoms to determine whether group classification
      affected risk of cognitive impairment or depressive symptoms. We controlled our
      analyses for disease duration and motor severity as measured by the Unified
      Parkinson Disease Rating Scale Part III motor score. RESULTS: There were no
      differences in any cognitive measure by side and type of initial motor symptoms.
      The right-sided onset tremor group had the lowest depressive symptom scores, and
      no patient in any group reported severe depressive symptoms. CONCLUSIONS: Our
      findings suggest that patterns of nigral cell loss correlating to the initial
      side and type of motor symptoms in PD are not related to the risk of later
      cognitive impairment. By contrast, patients with right-sided onset of tremor seem
      to have a lower risk of depressive symptoms than patients with other
      presentations.

PMID- 22960436
TI  - Effectiveness of the combination of memantine plus vitamin D on cognition in
      patients with Alzheimer disease: a pre-post pilot study.
AB  - OBJECTIVE: To determine whether treatment with memantine plus vitamin D is more
      effective than memantine or vitamin D alone in improving cognition among patients
      with Alzheimer disease (AD). METHODS: We studied 43 white outpatients (mean 84.7
      +/- 6.3 years; 65.1% women) with a new diagnosis of AD, who had not taken anti
      dementia drugs or vitamin D supplements. We prescribed memantine alone (n = 18),
      vitamin D alone (n = 17), or memantine plus vitamin D (n = 8) for an average of 6
      months. We assessed cognitive change with the Mini-Mental State Examination
      (MMSE). We used age, sex, pre-treatment MMSE score, and duration of treatment as
      covariables. RESULTS: Before treatment, the 3 groups had comparable MMSE scores.
      At 6 months, participants taking memantine plus vitamin D increased their MMSE
      score by 4.0 +/- 3.7 points (P = 0.034), while participants taking memantine
      alone remained stable (change of 0.0 +/- 1.8 points; P = 0.891), as did those
      taking vitamin D alone (-0.6 +/- 3.1 points; P = 0.504). Treatment with memantine
      plus vitamin D was associated with improvement in the MMSE score compared to
      memantine or vitamin D alone after adjustment for covariables (P < 0.01). Mixed
      regression analysis showed that the visit by combined treatments (memantine plus
      vitamin D) interaction was significant (P = 0.001), while memantine or vitamin D
      alone showed no effect. CONCLUSIONS: Patients with AD who took memantine plus
      vitamin D for 6 months had a statistically and clinically relevant gain in
      cognition, underlining possible synergistic and potentiating benefits of the
      combination.

PMID- 22960437
TI  - Self-reports of executive dysfunction in current ecstasy/polydrug Users.
AB  - OBJECTIVES/BACKGROUND: Ecstasy/polydrug users have exhibited deficits in
      executive functioning in laboratory tests. We sought to extend these findings by
      investigating the extent to which ecstasy/polydrug users manifest executive
      deficits in everyday life. METHODS: Forty-two current ecstasy/polydrug users, 18
      previous (abstinent for at least 6 months) ecstasy/polydrug users, and 50 non
      users of ecstasy (including both non-users of any illicit drug and some cannabis
      only users) completed the self-report Behavior Rating Inventory of Executive
      Function-Adult Version (BRIEF-A) measure. RESULTS: Current ecstasy/polydrug users
      performed significantly worse than previous users and non-users on subscales
      measuring inhibition, self-monitoring, initiating action, working memory,
      planning, monitoring ongoing task performance, and organizational ability.
      Previous ecstasy/polydrug users did not differ significantly from non-users. In
      regression analyses, although the current frequency of ecstasy use accounted for
      statistically significant unique variance on 3 of the 9 BRIEF-A subscales, daily
      cigarette consumption was the main predictor in 6 of the subscales. CONCLUSIONS:
      Current ecstasy/polydrug users report more executive dysfunction than do previous
      users and non-users. This finding appears to relate to some aspect of ongoing
      ecstasy use and seems largely unrelated to the use of other illicit drugs. An
      unexpected finding was the association of current nicotine consumption with
      executive dysfunction.

PMID- 22960438
TI  - The Coin-in-the-Hand Test and dementia: more evidence for a screening test for
      neurocognitive symptom exaggeration.
AB  - BACKGROUND: The Coin-in-the-Hand Test was developed to help clinicians
      distinguish patients who are neurocognitively impaired from patients who are
      exaggerating or feigning memory complaints. Previous findings have shown that
      participants asked to feign memory problems and patients suspected of malingering
      performed worse on the test than patients with genuine neurocognitive
      dysfunction. OBJECTIVE: We reviewed the literature on the Coin-in-the-Hand Test
      and evaluated test performance by 45 hospitalized patients who had dementia with
      moderately to severely impaired cognition. METHODS: We analyzed Coin-in-the-Hand
      Test scores, neuropsychological findings, and other data to determine whether
      demographic or neurocognitive variables affected Coin-in-the-Hand Test scores. We
      also calculated base rates of these scores and provided cutoff ranges for
      clinical use. RESULTS: Coin-in-the-Hand Test scores were independent of
      neurocognitive functioning, age, education level, and type of dementia. Base
      rates of scores suggest that a low cutoff can help differentiate between patients
      with true neurocognitive impairments and those exaggerating or feigning memory
      complaints. CONCLUSIONS: Both the literature and our findings show the Coin-in
      the-Hand Test to have potential as a quick and easy screening tool to detect
      neurocognitive symptom exaggeration. This test could effectively supplement
      commonly used neurocognitive screens such as the Mini-Mental State Examination,
      the Saint Louis University Mental Status Examination, and the Montreal Cognitive
      Assessment.

PMID- 22960439
TI  - A selective memory deficit caused by autoimmune encephalopathy associated with
      Hashimoto thyroiditis.
AB  - We report a longstanding selective memory deficit in a euthyroid 45-year-old
      woman who was being treated with levothyroxine for Hashimoto thyroiditis. The
      patient had complained of memory problems and deterioration of her concentration
      skills for about 2 years. Her endocrinologist thought that she was depressed. The
      patient's physical examination was normal. She scored a full 30 points on the
      Mini-Mental State Examination, but neuropsychological evaluation showed a
      significant deficit in her verbal memory. Routine blood tests and cerebrospinal
      fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic
      resonance imaging was normal. Electroencephalogram showed scarce intermittent
      bilateral multifocal theta waves. We increased the patient's daily dose of
      levothyroxine and started her on dexamethasone therapy. Five months later, we
      repeated the entire evaluation and found both her cognitive function and her
      electroencephalogram to be normal. Autoimmune encephalopathy associated with
      Hashimoto thyroiditis is already known to present with either stroke-like
      episodes or diffuse progressive deterioration. Our patient shows that the
      encephalopathy can present as a chronic selective memory deficit that can spare
      executive functions and short-term memory. This presentation can be missed or
      mistaken for depression, but can be diagnosed with a detailed neuropsychological
      evaluation.

PMID- 22960440
TI  - Hyposchematia without spatial neglect in 2 patients with lesions involving the
      insula.
AB  - BACKGROUND: : Hyposchematia is a rare variant of aschematia in which patients
      underestimate the size of part or all of their body. The term also describes an
      abnormality in drawing tasks, in which patients underestimate the size of 1 side
      of an image and draw it too small. Little is known about the neuroanatomy of the
      syndrome. CASE REPORTS: : We report 2 patients who developed contralateral
      hyposchematia without spatial neglect after suffering an ischemic lesion
      involving the right insula. Both patients felt that the left side of their face
      and their left arm and leg were disproportionately smaller than their right. On a
      drawing task, both patients drew the left sides of objects smaller than the
      right; they perseverated on the left sides of the images, for example, adding
      extra left-sided petals to a daisy. CONCLUSIONS: : In 2 reported patients, the
      cause of hyposchematia may be a lesion involving multiple insular circuits that
      affect the perception of extrapersonal space and self-related systems.

PMID- 22960441
TI  - Cognitive and behavioral phenotype of a young man with a chromosome 13 deletion
      del(13)(q21.32q31.1).
AB  - Cognitive, emotional, and behavioral characterizations have been reported for
      patients with a few chromosomal imbalances, but not for patients with a 13q
      deletion. We report the neuropsychological profile and specific linguistic,
      visual, spatial, constructional, and behavioral disabilities of a young man with
      a de novo chromosome 13 deletion (13)(q21.32)(q31.1). Karyotyping at 550 G-band
      resolution showed that the patient's parents did not share the deletion.
      According to array-comparative genomic hybridization, the deletion spanned about
      14 Mb and included 27 genes. A fluorescence in situ hybridization assay revealed
      an intact 13q telomere on the partially deleted chromosome. The patient had
      multiple morphologic and ophthalmologic anomalies. A brain magnetic resonance
      imaging study did not show gross brain defects. Neuropsychological testing showed
      an acceptable use of everyday language, but mild mental retardation, executive
      dysfunction, and very poor performance on visual, visuospatial, and
      constructional tasks. Establishing a neuropsychological profile for a patient
      with a specific genetic defect can help clinicians, parents, and teachers work to
      meet the patient's medical, academic, and behavioral needs.

PMID- 22960442
TI  - Methamphetamine-induced nitric oxide promotes vesicular transport in blood-brain
      barrier endothelial cells.
AB  - Methamphetamine's (METH) neurotoxicity is thought to be in part due to its
      ability to induce blood-brain barrier (BBB) dysfunction. Here, we investigated
      the effect of METH on barrier properties of cultured rat primary brain
      microvascular endothelial cells (BMVECs). Transendothelial flux doubled in
      response to METH, irrespective of the size of tracer used. At the same time,
      transendothelial electrical resistance was unchanged as was the ultrastructural
      appearance of inter-endothelial junctions and the distribution of key junction
      proteins, suggesting that METH promoted vesicular but not junctional transport.
      Indeed, METH significantly increased uptake of horseradish peroxidase into
      vesicular structures. METH also enhanced transendothelial migration of
      lymphocytes indicating that the endothelial barrier against both molecules and
      cells was compromised. Barrier breakdown was only observed in response to METH at
      low micromolar concentrations, with enhanced vesicular uptake peaking at 1 MUM
      METH. The BMVEC response to METH also involved rapid activation of endothelial
      nitric oxide synthase and its inhibition abrogated METH-induced permeability and
      lymphocyte migration, indicating that nitric oxide was a key mediator of BBB
      disruption in response to METH. This study underlines the key role of nitric
      oxide in BBB function and describes a novel mechanism of drug-induced fluid-phase
      transcytosis at the BBB.

PMID- 22960443
TI  - The spontaneously hypertensive and Wistar Kyoto rat models of ADHD exhibit sub
      regional differences in dopamine release and uptake in the striatum and nucleus
      accumbens.
AB  - The most widely used animal model of attention-deficit/hyperactivity disorder
      (ADHD) is the spontaneously hypertensive rat (SHR/NCrl), which best represents
      the combined subtype (ADHD-C). Recent evidence has revealed that a progenitor
      strain, the Wistar Kyoto from Charles River Laboratories (WKY/NCrl), is useful as
      a model of the inattentive subtype (ADHD-PI) and the Wistar Kyoto from Harlan
      Laboratories (WKY/NHsd) and the Sprague Dawley (SD) have been suggested as
      controls. Dopamine (DA) dysfunction in the striatum (Str) and nucleus accumbens
      core (NAc) is thought to play a significant role in the pathophysiology of ADHD
      but data obtained with the SHR is equivocal. Using high-speed chronoamperometric
      recordings with carbon fiber microelectrodes, we found that the SHR/NCrl
      displayed decreased KCl-evoked DA release versus the WKY/NCrl model of ADHD-PI in
      the dorsal Str. The WKY/NCrl and the WKY/NHsd control did not differ from each
      other; however, the control SD released less DA than the WKY/NCrl model of ADHD
      PI in the dorsal Str and less than the control WKY/NHsd in the intermediate Str.
      The SHR/NCrl had faster DA uptake in the ventral Str and NAc versus both control
      strains, while the WKY/NCrl model of ADHD-PI exhibited faster DA uptake in the
      NAc versus the SD control. These results suggest that increased surface
      expression of DA transporters may explain the more rapid uptake of DA in the Str
      and NAc of these rodent models of ADHD.

PMID- 22960444
TI  - Phenylpiperazine derivatives with selectivity for dopamine D3 receptors modulate
      cocaine self-administration in rats.
AB  - This study examined cocaine self-administration after pretreatments with three
      structurally related compounds that bind selectively to dopamine D3 receptors
      (D3Rs) relative to the D2 receptor subtype (D2Rs) and exhibit varying intrinsic
      activities in the forskolin-stimulated adenylyl cyclase assay. The compounds are:
      a) WC10, a D3R weak partial agonist/antagonist with 42-fold D3R:D2R selectivity,
      b) WC26, a 51-fold selective D3R partial agonist, c) WC44, a 23-fold selective
      D3R agonist. Rats were stabilized on a multiple variable-interval 60-s (VI60)
      schedule with alternating components of sucrose (45 mg pellets) or cocaine
      reinforcement (0.375 mg/kg, IV) and then tested for effects of the WC compounds
      (0.0, 1.0, 3.0, 5.6, or 10.0 mg/kg, IP). Another cohort was trained to self
      administer cocaine (0.75 mg/kg, IV) on a VI60 schedule then tested with various
      doses of cocaine available (0.0-1.5 mg/kg, IV) following pretreatment with WC10
      (5.6 or 10.0 mg/kg) or WC44 (10.0 mg/kg). WC10 and WC26 decreased both cocaine
      and sucrose reinforcement rates at the 10.0 mg/kg dose, whereas WC44 decreased
      only cocaine reinforcement rate at this dose. Furthermore, WC26 and WC44
      increased response latency for cocaine but not sucrose. In the cocaine dose
      response experiment, WC10 and WC44 flattened the dose-effect function of cocaine
      reinforcement rate. All compounds decreased spontaneous locomotion. WC10 and WC26
      also reduced cocaine-induced locomotion. These results support the targeting of
      D3Rs for treatments for cocaine dependence. WC26 and WC44, in particular, show
      promise as they increased the latency to respond for cocaine but not sucrose,
      suggesting selective reduction of the motivation for cocaine.

PMID- 22960445
TI  - Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative
      stress in hippocampus, cerebellum, and brainstem.
AB  - Ethanol is one of the most commonly abused substances, and oxidative stress is an
      important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1
      (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates
      the role of brain CYP2E1 in the susceptibility of certain brain regions to
      ethanol neurotoxicity. Male Wistar rats were intragastrically treated with
      ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic
      activity in various brain regions were respectively assessed by immunoblotting,
      quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC-MS. The
      generation of reactive oxygen species (ROS) was analyzed using a laser confocal
      scanning microscope. The hippocampus, cerebellum, and brainstem were selectively
      damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH)
      activity and histopathological analysis. Ethanol markedly increased the levels of
      CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum.
      CYP2E1 protein and activity were significantly increased by ethanol in the
      brainstem, with no change in mRNA expression. ROS levels induced by ethanol
      paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and
      white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was
      positively correlated with the damage to the hippocampus, cerebellum, and
      brainstem. These results suggest that the selective sensitivity of brain regions
      to ethanol neurodegeneration may be attributed to the regional and cellular
      specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may
      attenuate ethanol-induced oxidative stress via ROS generation.

PMID- 22960446
TI  - Neonatal exposure to benzo[a]pyrene decreases the levels of serum testosterone
      and histone H3K14 acetylation of the StAR promoter in the testes of SD rats.
AB  - Although benzo[a]pyrene (BaP) is an environmental endocrine disrupter, it has
      been unclear whether neonatal exposure to BaP affects the testosterone level and,
      if so, whether this influence persists into adulthood. In this present study, we
      gave neonatal rats (through oral gavages) doses of 0, 5, 10, or 25mg/kg day of
      BaP in corn oil from postnatal day 1 (PND 1) to PND 7. The rats were sacrificed
      at PND 8, PND 35, and PND 90. BaP exposure was confirmed through the induction of
      liver and testis CYP1A1 mRNA expression at PND 8 (i.e., immediately after
      exposure). The testicular daily sperm production and the sperm counts of the
      epididymis cauda at PND 90 were significantly lower than those of the control.
      The serum testosterone levels decreased markedly at PND 8, PND 35, and PND 90
      after neonatal BaP exposure relative to those of the control. The mRNA
      expressions of StAR also decreased relative to those of the control at PND 8, PND
      35, and PND 90, although the mRNA expressions of P450c17 and 17beta-HSD were
      suppressed significantly only at PND 8. To further elucidate the mechanism of the
      persistent decrease in the mRNA expression of StAR, we determined the histone
      acetylation level in the StAR promoter. The extent of acetylation of H3K14 in the
      determined region decreased after neonatal exposure to BaP; this phenomenon
      persisted to the adult stage. Our results indicate that neonatal exposure to BaP
      damages testosterone production and sperm counts in the long term, possibly as a
      result of epigenetic regulation in the StAR promoter region.

PMID- 22960447
TI  - Effects of aluminum on the energetic substrates in neotropical freshwater
      Astyanax bimaculatus (Teleostei: Characidae) females.
AB  - We investigated the effects of acidic pH and acute aluminum (Al) exposure on the
      metabolic substrates of Astyanax bimaculatus, and on the ability of these animals
      to recover in clean water. After an acclimation period, sexually mature A.
      bimaculatus females were sorted into six glass aquaria with three experimental
      groups: control in neutral pH (7.0), acidic pH (5.5), and Al (0.5 mg.L(-1)) in
      acidic pH (5.5). After a 96 h treatment, 10 animals from each experimental group
      were sampled and the rest were returned to clean water in neutral pH without Al
      for a recovery period of 96 h. The acidic pH, either alone or combined with Al,
      decreased T4 levels, whereas Al exposure increased T3 levels. Recovery of T3
      levels occurred after 96 h. Al exposure decreased ovary and plasma proteins,
      muscle glycogen contents, and hepatic lipids due to lipoperoxidation. In the
      recovery phase, lipids decreased in most tissues, probably to re-establish ovary
      protein and hepatic glycogen. A. bimaculatus prioritized the use of energetic
      resources during acclimatization to Al instead of prioritizing reproduction,
      thereby avoiding the ovulation of impaired eggs.

PMID- 22960448
TI  - Gene expression of inflammatory mediators induced by jararhagin on endothelial
      cells.
AB  - Snake venom metalloproteinases (SVMP) are abundant toxins in venoms of viper
      snakes and play a relevant role in the complex and multifactorial tissue damage
      characteristic of Viperidae envenoming. Jararhagin, a SVMP isolated from Bothrops
      jararaca venom, induces a fast onset hemorrhagic lesions acting directly on the
      capillary vessels, which are disrupted by toxin adhesion and degradation of
      extracellular matrix proteins like collagen IV. Jararhagin also triggers
      inflammatory response, where endothelial cells are activated, resulting in the
      enhanced rolling of circulating leukocytes, nitric oxide generation, prostacyclin
      production and pro-inflammatory cytokines release. Jararhagin also decreases
      endothelial cells viability inducing apoptosis (in vitro studies). In the present
      study we attempted to correlate the effect of sub-apoptotic doses of jararhagin
      on human umbilical vein endothelial cells (HUVECs) and gene expression of pro
      inflammatory mediators, using microarray assay, real time PCR and detection of
      specific proteins on HUVEC surface or released in the medium. Jararhagin was
      effective in activate and up-regulate the gene expression of different mediators
      such as E-selectin, VCAM-1, IL-8, CD69, Ang-2 and MMP-10. Despite the increase in
      expression of genes coding for such molecules, jararhagin did not induce
      increased concentrations of E-selectin, VCAM-1 and IL-8 produced or released by
      endothelial cells. In conclusion, jararhagin is able to activate pro-inflammatory
      gene transcription on endothelial cells however this stimulus is not sufficient
      to result in the consequent expression of pro-inflammatory effectors molecules
      like E-selectin, VCAM-1 and IL-8. The time courses of these events, as well as
      the doses of jararhagin are important points to be addressed herein.

PMID- 22960449
TI  - Shiga toxins.
AB  - Shiga toxins are virulence factors produced by the bacteria Shigella dysenteriae
      and certain strains of Escherichia coli. There is currently no available
      treatment for disease caused by these toxin-producing bacteria, and understanding
      the biology of the Shiga toxins might be instrumental in addressing this issue.
      In target cells, the toxins efficiently inhibit protein synthesis by inactivating
      ribosomes, and they may induce signaling leading to apoptosis. To reach their
      cytoplasmic target, Shiga toxins are endocytosed and transported by a retrograde
      pathway to the endoplasmic reticulum, before the enzymatically active moiety is
      translocated to the cytosol. The toxins thereby serve as powerful tools to
      investigate mechanisms of intracellular transport. Although Shiga toxins are a
      serious threat to human health, the toxins may be exploited for medical purposes
      such as cancer therapy or imaging.

PMID- 22960450
TI  - Investigation of extraction and analysis techniques for Lyngbya wollei derived
      Paralytic Shellfish Toxins.
AB  - Paralytic Shellfish Toxins (PSTs) are highly toxic metabolic by-products of
      cyanobacteria and dinoflagellates. The filamentous cyanobacterium Lyngbya wollei
      produces a unique set of PSTs, including L. wollei toxins (LWT) 1-6. The accurate
      identification and quantification of PSTs from Lyngbya filaments is challenging,
      but critical for understanding toxin production and associated risk, as well as
      for providing baseline information regarding the potential for trophic transfer.
      This study evaluated several approaches for the extraction and analysis of PSTs
      from field-collected L. wollei dominated algal mats. Extraction of PSTs from
      lyophilized Lyngbya biomass was assessed utilizing hydrochloric acid and acetic
      acid at concentrations of 0.001-0.1 M. Toxin profiles were then compared
      utilizing two analysis techniques: pre-column oxidation (peroxide and periodate)
      High Performance Liquid Chromatography (HPLC) with Fluorescence (FL) detection
      and LC coupled with Mass Spectrometry (MS). While both acid approaches
      efficiently extracted PSTs, hydrochloric acid was found to convert the less toxic
      LWT into the more toxic decarbamoylgonyautoxins 2&3 (dcGTX2&3) and
      decarbamoylsaxitoxin (dcSTX). In comparison, extraction with 0.1 M acetic acid
      preserved the original toxin profile and limited the presence of interfering co
      extractants. Although pre-chromatographic oxidation with HPLC/FL was relatively
      easy to setup and utilize, the method did not resolve the individual constituents
      of the L. wollei derived PST profile. The LC/MS method allowed characterization
      of the PSTs derived from L. wollei, but without commercially available LWT 1-6
      standards, quantitation was not possible for the LWT. In future work, evaluation
      of the risk associated with L. wollei derived PSTs will require commercially
      available standards of LWT 1-6 for accurate determinations of total PST content
      and potency.

PMID- 22960451
TI  - Inhibition in vivo of the activity of botulinum neurotoxin A by small molecules
      selected by virtual screening.
AB  - To search for small molecular size inhibitors of botulinum neurotoxin A (BoNT/A)
      endopeptidase activity, we have screened the NCI library containing about 1
      million structures against the substrate binding pocket of BoNT/A. Virtual
      screening (VS) was performed with the software Glide (Grid-based ligand docking
      energetics) and the findings were confirmed by AutoDock. Ten compounds were found
      that had favorable energetic and glide criteria and 5 of these compounds were
      selected for their ability to protect mice in vivo against a lethal dose of
      BoNT/A. Each compound was incubated at different molar excesses with a lethal
      dose of the toxin and then the mixture injected intravenously into mice. At 4690
      M excess, compounds NSC94520 and NSC99639 protected all (100%) the mice from
      lethal toxicity. Compounds NSC48461 and NSC627733 gave 75% protection. Compound
      NSC348884 showed the least inhibition of toxicity allowing only a fraction (25%)
      of the mice to survive challenge with a lethal dose; and in the case of the mice
      that did not survive there was a considerable delay of mortality. At 2400 M
      excess compounds NSC94520 remained fully protective while and NSC99639 afforded
      75% protection and at 1200 M excess each of these two compounds gave 50%
      protection. The two compounds gave no protection at 600 or less molar excess.
      When each compound was administered intravenously at 4690 M excess at different
      times (from 1 h to 6 h) after the intravenous injection of the active toxin, none
      of the compounds was able to protect the animals from toxicity. The findings show
      the value of VS in identifying potential inhibitors of the toxin for further
      development and improvement.

PMID- 22960452
TI  - Ecotoxicity evaluation and removal of sulfonamides and their acetylated
      metabolites during conventional wastewater treatment.
AB  - The present study describes the evaluation of the risk posed by the occurrence of
      sulfonamides (SAs) in wastewaters. A fully automated analytical method based on
      on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (on
      line SPE-LC-MS/MS) was developed, validated and applied for the analysis of
      sixteen SAs and, for the first time in wastewaters and sewage sludge, five of
      their acetylated metabolites. Influent and effluent samples from twenty two
      different wastewater treatment plants (WWTPs) in Catalonia (Spain) and sewage
      sludge from fifteen of them were analyzed; removal rates (RE%) and half-lives
      (t(1/2)) for each SA were calculated. The estimated correlations between RE% and
      to the hydraulic retention time (HRT) of the different plants indicated no clear
      influence of HRT on removals. Sulfamethoxazole (SMX), sulfapyridine (SPY) and
      their corresponding acetylated metabolites were detected with the highest
      frequencies of detection and at the highest concentrations. The ecotoxicity of
      both SPY and AcSPY was evaluated for the first time through bioluminescent
      inhibition assays, resulting in a higher toxicity being attributed to the
      metabolite. Finally, the potential environmental risk posed by the levels of SAs
      detected was evaluated calculating the hazard quotients (HQ) to different non
      target aquatic organisms in treated wastewaters. SMX was the only SA posing a
      risk to algae, with an HQ>10.

PMID- 22960453
TI  - Existing and emerging mitochondrial-targeting therapies for altering Parkinson's
      disease severity and progression.
AB  - A case in support of mitochondrial dysfunction in Parkinson's disease (PD) has
      received support from animal modeling studies as well as studies performed on
      biopsied material taken from living and deceased patients. This body of growing
      evidence for mitochondrial involvement in PD pathogenesis has led to many
      potential therapeutic endeavors aimed at altering the course of progressive PD,
      as well as highlighting the biomarker potential to screen for genetic, molecular
      and metabolic constituents of mitochondria, to identify those most at risk for
      developing the disease. Here we present the results from a comprehensive treatise
      of the published studies to date that have attempted to make use of the growing
      information on mitochondrial function for designing neuroprotective and
      neurorescuing therapies applied to PD-implicated disease processes. Additionally,
      studies affirmed that mitochondrial-targeting interventions intended for use as
      an annex to mainstay pharmacological treatments also show benefits in slowing PD
      progression. Both drug-related and gene-based therapeutic approaches are
      discussed, with evidence presented from both animal modeling studies as well as
      product assessments undergoing various phases of clinical trial progression.

PMID- 22960454
TI  - Natriuretic peptides regulate heart rate and sinoatrial node function by
      activating multiple natriuretic peptide receptors.
AB  - Natriuretic peptides, including BNP and CNP, elicit their effects via two
      guanylyl cyclase-linked receptors denoted NPR-A and NPR-B as well as a third
      receptor, NPR-C. The relative contributions of these receptors to the overall
      effects of NPs on heart rate (HR) and sinoatrial node (SAN) function are very
      poorly understood. The effects of BNP and CNP (10-500 nM) on HR and SAN myocyte
      spontaneous action potential (AP) firing were studied using wildtype mice and
      mice lacking functional NPR-C receptors (NPR-C(-/-)). In basal conditions and 10
      nM doses of the beta-adrenergic receptor (beta-AR) agonist isoproterenol (ISO)
      BNP and CNP increased HR and AP firing in SAN myocytes. The NPR-C selective
      agonist cANF (10-500 nM) had no effects in basal conditions, but decreased HR and
      SAN AP frequency in the presence of ISO. These effects of cANF were completely
      absent in NPR-C(-/-) mice. Strikingly, in the presence of 1 MUM doses of ISO, BNP
      and CNP switched to causing decreases in HR and SAN AP frequency. These decreases
      were not as large as those elicited by cANF and were absent in NPR-C(-/-) hearts,
      where BNP instead elicited a further increase in HR. Inhibition of NPR-A with
      A71915, in the presence of 1 MUM ISO, enabled BNP to signal exclusively through
      NPR-C and to decrease HR as effectively as cANF. Together these data demonstrate
      that BNP and CNP affect HR and SAN function by activating multiple receptor
      subtypes. NPR-A/B mediate increases in HR and SAN function, but these effects are
      opposed by NPR-C, which plays an increasingly important signaling role in the
      presence of beta-AR stimulation.

PMID- 22960456
TI  - Environmental aspects of eucalyptus based ethanol production and use.
AB  - A renewable biofuel economy is projected as a pathway to decrease dependence on
      fossil fuels as well as to reduce greenhouse gases (GHG) emissions. Ethanol
      produced on large-scale from lignocellulosic materials is considered the
      automotive fuel with the highest potential. In this paper, a life cycle
      assessment (LCA) study was developed to evaluate the environmental implications
      of the production of ethanol from a fast-growing short rotation crop (SRC):
      eucalyptus as well as its use in a flexi-fuel vehicle (FFV). The aim of the
      analysis was to assess the environmental performance of three ethanol based
      formulations: E10, E85 and E100, in comparison with conventional gasoline. The
      standard framework of LCA from International Standards Organization was followed
      and the system boundaries included the cultivation of the eucalyptus biomass, the
      processing to ethanol conversion, the blending with gasoline (when required) and
      the final use of fuels. The environmental results show reductions in all impact
      categories under assessment when shifting to ethanol based fuels, excluding
      photochemical oxidant formation, eutrophication as well as terrestrial and marine
      ecotoxicity which were considerably influenced by upstream activities related to
      ethanol manufacture. The LCA study remarked those stages where the researchers
      and technicians need to work to improve the environmental performance. Special
      attention must be paid on ethanol production related activities, such as on-site
      energy generation and distillation, as well as forest activities oriented to the
      biomass production. The use of forest machinery with higher efficiency levels,
      reduction of fertilizers dose and the control of diffuse emissions from the
      conversion plant would improve the environmental profile.

PMID- 22960455
TI  - Role of inositol 1,4,5-trisphosphate in the regulation of ventricular Ca(2+)
      signaling in intact mouse heart.
AB  - Inositol 1,4,5-trisphosphate (InsP(3)R)-mediated Ca(2+) signaling is a major
      pathway regulating multiple cellular functions in excitable and non-excitable
      cells. Although InsP(3)-mediated Ca(2+) signaling has been extensively described,
      its influence on ventricular myocardium activity has not been addressed in
      contracting hearts at the whole-organ level. In this work, InsP(3)-sensitive
      intracellular Ca(2+) signals were studied in intact hearts using laser scanning
      confocal microscopy and pulsed local-field fluorescence microscopy. Intracellular
      [InsP(3)] was rapidly increased by UV flash photolysis of membrane-permeant caged
      InsP(3). Our results indicate that the basal [Ca(2+)] increased after the flash
      photolysis of caged InsP(3) without affecting the action potential (AP)-induced
      Ca(2+) transients. The amplitude of the basal [Ca(2+)] elevation depended on the
      intracellular [InsP(3)] reached after the UV flash. Pretreatment with ryanodine
      failed to abolish the InsP(3)-induced Ca(2+) release (IICR), indicating that this
      response was not mediated by ryanodine receptors (RyR). Thapsigargin prevented
      Ca(2+) release from both RyR- and InsP(3)R-containing Ca(2+) stores, suggesting
      that these pools have similar Ca(2+) reuptake mechanisms. These results were
      reproduced in acutely isolated cells where photorelease of InsP(3) was able to
      induce changes in endothelial cells but not in AP-induced transients from
      cardiomyocytes. Taken together, these results suggest that IICR does not directly
      regulate cardiac excitation-contraction coupling. To our knowledge, this is the
      first demonstration of IICR in intact hearts. Consequently, our work provides a
      reference framework of the spatiotemporal attributes of the IICR under
      physiological conditions.

PMID- 22960457
TI  - Alterations in prefrontal cortical serotonin and antidepressant-like behavior in
      a novel C3H/HeJxDBA/2J recombinant inbred mouse strain.
AB  - In the present study, two genetically related inbred mouse strains selectively
      bred for high and low fear-sensitized acoustic startle reflex (FSS) were assessed
      in the forced swim test model of anti-depressant action and central monoamine
      concentrations in several brain regions were investigated. These mice were
      generated through backcrossing C3H/HeJ mice on DBA/2J mice, followed by
      inbreeding for several generations. The high-FSS and low-FSS strains are known to
      differ in their acquisition and extinction of fear following auditory fear
      conditioning. Significantly increased concentrations of 5-HT and its metabolite 5
      HIAA were observed in the medial prefrontal cortex (mPFC) but not in the
      hypothalamus, striatum, hippocampus, amygdala, or midbrain of high-FSS mice
      compared to low-FSS mice. In addition the concentration of DOPAC, the major
      metabolite of dopamine was also significantly increased in the mPFC. Furthermore,
      the high-FSS mice displayed significantly higher levels of immobility in the
      forced swim test but not the tail suspension test in comparison to the low-FSS
      group. The mPFC is not only important in the regulation of fear extinction, but
      also a key region of interest in the study of depression and maintenance of
      depressive-like behaviors. These data implicate serotonergic modulation in the
      mPFC in the maintenance of antidepressant-like behavior in a highly fearful mouse
      strain.

PMID- 22960459
TI  - In vitro clastogenicity and phototoxicity of fullerene (C(60)) nanomaterials in
      mammalian cells.
AB  - Carbon nanomaterials such as carbon nanotubes, graphene, and fullerenes (C(60))
      are widely used in industry. Because of human health concerns, their toxic
      potential has been examined in vivo and in vitro. Here we used mammalian cells to
      examine the in vitro clastogenicity as well as the phototoxicity of C(60). While
      C(60) induced no structural chromosome aberrations in CHL/IU cells at up to
      5mg/ml (the maximum concentration tested), it significantly induced polyploidy at
      2.5 and 5mg/ml with and without metabolic activation. In BALB 3T3 cells, C(60)
      showed no phototoxic potential but the anatase form of titanium oxide did. Since
      insoluble nanomaterials cause polyploidy by blocking cytokinesis rather than by
      damaging DNA, we concluded that the polyploidy induced by C(60) in CHL/IU cells
      was probably due to non-DNA interacting mechanisms.

PMID- 22960460
TI  - Color and translucency of zirconia ceramics, human dentine and bovine dentine.
AB  - OBJECTIVES: Evaluate color and translucency of both non-colored and colored
      zirconia ceramics and compare them with corresponding properties of human
      dentine. METHODS: 0.5mm thick samples of human (MSHD) and bovine (MSBD) dentine
      were obtained from 5 extracted human anterior maxillary teeth and 5 bovine
      incisors, respectively. The zirconia systems evaluated (0.5mm samples) were: (1)
      IPS e.max((r)) ZirCAD sintered samples: (a) regular (ZC1); (b) colored - coloring
      liquid CL2 (ZC2); (2) LAVATM Zirconia sintered samples: (a) regular (LV1); (b)
      colored - coloring liquid FS3 (LV2). Translucency parameter (TP) and
      DeltaE(ab)(*) and DeltaE(00) color differences (with respect to the MSHD) were
      calculated. Spectral reflectance curves were compared using the VAF coefficient.
      RESULTS: Reflectance spectral behaviour of MSBD and MSHD were similar
      (VAF=99.3%). All zirconia samples showed higher spectral reflectance values than
      the MSHD. Lightness values obtained for all zirconia ceramics (especially LV)
      were higher than MSHD and MSBD. The range of color differences, with respect to
      MSHD, was 6.9-20.5 for DeltaE(ab)(*) and 4.9-15.6 for DeltaE(00). Colored samples
      showed lower color differences with respect to MSHD. The highest TP values were
      found for IPS e.max((r)) ZirCAD system and the lowest for LAVATM Zirconia system.
      In terms of translucency, MSHD, MSBD and zirconia ceramics showed no
      statistically significant differences. CONCLUSIONS: In terms of translucency, the
      studied zirconia systems could satisfactorily replace the human dentine within a
      dental restoration but, in order to produce a clinically acceptable match, it is
      necessary to carefully adjust the color of these systems.

PMID- 22960461
TI  - Effects of xylitol mouthrinse on Streptococcus mutans.
AB  - OBJECTIVES: This study aimed to measure the effect of xylitol mouthrinse on
      salivary Streptococcus mutans counts. METHODS: Subjects in the study group (n =
      25) used xylitol mouthrinse for 4 weeks, while another group (n = 25) used
      saccharine mouthrinse. S. mutans were measured before and after intervention.
      RESULTS: At the baseline the mean S. mutans scores were 3.9 (SE = 0.03) and 3.9
      (0.04) for the xylitol group and control group respectively, while the scores
      were 2.8 (0.13) and 3.9 (0.07) after the intervention. Significant reductions (p
      < 0.01) in the scores of S. mutans were found after the four week use of xylitol
      mouthrinse. CONCLUSIONS: Significant reductions in the scores of S. mutans were
      found after the four week use of 20% xylitol mouthrinse. The bacteriostatic
      effect of xylitol mouthrinse on S. mutans may be comparable to other xylitol
      products. Further studies are needed to confirm both the short and long term
      effects of xylitol mouthrinse.

PMID- 22960462
TI  - Scotland launches consultation on lowering drink driving limit.

PMID- 22960458
TI  - Behavioral effects of chronic methamphetamine treatment in HIV-1 gp120 transgenic
      mice.
AB  - Methamphetamine (METH) dependence is frequently comorbid with HIV infection. Both
      factors are independently characterized by inhibitory deficits, which may
      manifest as increased motor activity, inappropriate perseverative behavior, and
      elevated exploratory responses to novel stimuli, but the effect of combined METH
      exposure and HIV is not well understood. In this study, we administered a chronic
      escalation/binge regimen of METH or vehicle treatment to wildtype (WT) or
      transgenic (tg) mice expressing the HIV-1 gp120 envelope protein and quantified
      disinhibition during the 7 days following drug withdrawal. We hypothesized that
      gp120tg mice administered chronic METH would exhibit more pronounced inhibitory
      deficits compared to vehicle-treated WT or gp120tg animals. Our results showed
      that METH treatment alone increased novel object interaction while female METH
      treated gp120tg mice exhibited the highest level of exploration (holepoking)
      compared to other female mice. Transgenic mice exhibited fewer rears relative to
      WT, slightly less locomotion, and also demonstrated a trend toward more
      perseverative motor patterns. In summary, both METH treatment and gp120
      expression may modify inhibition, but such effects are selective and dependent
      upon variations in age and sex that could impact dopamine and frontostriatal
      function. These findings illustrate the need to improve our knowledge about the
      combined effects of HIV and substance use and facilitate improved treatment
      methods for comorbid disease and drug dependence.

PMID- 22960463
TI  - Risks of acupuncture range from stray needles to pneumothorax, finds study.

PMID- 22960464
TI  - Andrew Lansley: unlucky or incompetent?

PMID- 22960465
TI  - Friend or foe: can doctors trust Jeremy Hunt with the NHS?

PMID- 22960467
TI  - Iliopsoas abscess--a review and update on the literature.
AB  - Iliopsoas abscess is a rare condition with a varied symptomology and aetiology.
      Patients with this condition often present in different ways to different
      specialities leading to delays in diagnosis and management. Recent advances in
      the radiological diagnosis of this traditionally rare abscess have highlighted
      that there is a lack of evidence relating to its aetiology, symptomology,
      investigation and management. This article reviews the currently available
      literature to present a concise and systematic review of iliopsoas abscess.

PMID- 22960466
TI  - Differential actions of isoflurane and ketamine-based anaesthetics on cochlear
      function in the mouse.
AB  - Isoflurane is a volatile inhaled anaesthetic widely used in animal research, with
      particular utility for hearing research. Isoflurane has been shown to blunt
      hearing sensitivity compared with the awake state, but little is known about how
      isoflurane compares with other anaesthetics with regard to hair cell transduction
      and auditory neurotransmission. The current study was undertaken in C57Bl/6J and
      C129/SvEv strains of mice to determine whether isoflurane anaesthesia affects
      hearing function relative to ketamine-based anaesthesia. Cochlear function and
      central auditory transmission were assessed using auditory brainstem response
      (ABR) and distortion product otoacoustic emission (DPOAE), comparing thresholds
      and input/output functions over time, for isoflurane vs.
      ketamine/xylazine/acepromazine anaesthesia. ABR thresholds at the most sensitive
      region of hearing (16 kHz) were initially higher under isoflurane anaesthesia.
      This reduced hearing sensitivity worsened over the 1 h study period, and also
      became evident with broadband click stimulus. Ketamine anaesthesia provided
      stable ABR thresholds. Although the growth functions were unchanged over time for
      both anaesthetics, the slopes under isoflurane anaesthesia were significantly
      less. Cubic (2f(1)-f(2)) DPOAE thresholds and growth functions were initially
      similar for both anaesthetics. After 60 min, DPOAE thresholds increased for both
      groups, but this effect was significantly greater with ketamine anaesthesia. The
      isoflurane-mediated increase in ABR thresholds over time is attributable to
      action on cochlear nerve activation, evident as a right-shift in the P1-N1
      input/output function compared to K/X/A. The ketamine-based anaesthetic produced
      stable ABR thresholds and gain over time, despite a right-shift in the outer hair
      cell - mediated DPOAE input/output function.

PMID- 22960468
TI  - Skin graft meshing, over-meshing and cross-meshing.
AB  - INTRODUCTION: Split skin grafts (SSGs) are often meshed to increase their size
      and allow exudate to escape. We investigated the expansion obtained with meshing,
      and the possibility of re-meshing skin that has already been meshed
      ("overmeshing"). Both useful and inadvisable permutations are illustrated.
      MATERIAL AND METHODS: Thin porcine SSGs were sideways meshed, or meshed with
      ratios of 1.5:1 and 3:1. Subsequently samples were over-meshed in a variety of
      ratios and directions. All grafts were maximally expanded and their areas
      calculated. RESULTS: Meshed skin did not expand as much as suggested by the
      ratios displayed on dermacarriers. A 1:1.5 dermacarrier produced an area
      expansion of 1.36*, and a 1:3 meshing apparatus produced only a 1.80*area
      expansion. Several combinations of twice-meshed SSGs maintained integrity as long
      as over-meshing was done in the axis of initial meshing. Up to 2.3*expansion was
      obtained, by following a 1:1.5 mesh with a 1:3 mesh. We term this procedure as
      "overmeshing". Re-meshing in a direction orthogonal to initial meshing (cross
      meshing) cut the skin into small pieces. CONCLUSION: Over-meshing a SSG can allow
      considerable further expansion, facilitating overgrafting of donor sites or
      simply increasing the area that can be covered with the existing harvested skin.

PMID- 22960470
TI  - Fundamental differences in visual search with verbal and pictorial cues.
AB  - Three experiments examined the effects of using informative verbal and pictorial
      cues on participants' abilities to perform visual search. By providing
      participants with more time to encode the cues than had been used previously, all
      three experiments revealed long-lasting pictorially cued search advantages that
      stabilized over time. Experiments 1 and 3 demonstrated that searching for
      changing targets with pictorial cues was equivalent to searching for the same
      target over multiple trials in which target-switching costs would have been
      minimized. Experiment 3 additionally revealed that earlier evidence of
      pictorially cued search advantages was not due to inadequately equating the
      amount of information contained in the cues or uncertainty about when the search
      display would appear. Together, the data suggest that there are fundamental
      differences in the ability of participants to engage in visual search when the
      targets are identified with verbal, as opposed to pictorial, cues even when
      participants have sufficient time to fully encode the cues.

PMID- 22960469
TI  - Proteomic characterization of a novel structural protein ORF5a of porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) emerged in the late
      1980s in both Europe and North America is an arterivirus causing great economic
      losses in the pig industry worldwide. Recently, a novel structural protein,
      ORF5a, encoded by an alternative ORF of a subgenomic mRNA encoding the major
      envelope glycoprotein, GP5, has been discovered in all arteriviruses, suggesting
      its important role in arterivirology. The present study attempted to investigate
      compensatory changes of cellular gene expression in natural target cells
      regulated by the ORF5a. We thus established sublines of PAM cells to stably
      express the PRRSV ORF5a protein and assessed alterations in cellular protein
      productions of ORF5a-expressing PAM (PAM-ORF5a) cells at different time courses
      by the use of proteomic analysis. A total of 36 protein spots were initially
      found to be differentially expressed in PAM-ORF5a cells compared with normal PAM
      cells by high-resolution two-dimensional gel electrophoresis (2DE). Of these
      spots, 16 protein spots with statistically significant alteration, including 13
      up-regulated and 3 down-regulated protein spots, were picked out for subsequent
      protein identification by peptide mass fingerprinting after matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS). The
      altered cellular proteins identified in this study were grouped into the
      functions associated with a variety of cellular processes such as cell growth,
      cytoskeleton networks and cell communication, metabolism, protein biosynthesis,
      RNA processing, and transportation. The proteomics data will provide valuable
      information for better understanding the specific cellular response to the novel
      ORF5a protein during PRRSV replication.

PMID- 22960471
TI  - Differential cell-specific cytotoxic responses of oral cavity cells to tobacco
      preparations.
AB  - To examine the effects of standardized (reference) tobacco preparations on human
      oral cavity cells, two oral squamous cell carcinoma cell lines (101A, 101B) and
      normal human gingival epithelial cells (HGEC) were treated with cigarette smoke
      total particulate matter (TPM), smokeless tobacco extracted with complete
      artificial saliva (ST/CAS), or whole-smoke conditioned media (WS-CM). EC-50
      values, as determined by sulforhodamine B assays, varied among the cell types and
      agents. When normalized to nicotine content, cytotoxicity for WS-CM and TPM was
      higher compared to that observed with ST/CAS. Nicotine alone had no or only
      minimal cytotoxicity for all cell types in the applied range. Activation of pro
      apoptotic caspase-3 was examined in all cell types at their respective EC-50
      doses for the three agents. TPM, but not ST/CAS or WS-CM significantly activated
      caspase-3 in all three cell types. Fluorescence-activated cell sorting (FACS) for
      expression of the early apoptosis marker Annexin V and for nuclear staining by 7
      aminoactinomycin (7-AAD) revealed different extents of apoptosis versus non
      apoptotic cell death for the three agents. These data characterize differential
      responses of normal and malignant oral cells after exposure to TPM, ST/CAS, or WS
      CM. They assist in understanding differential effects of combustible versus non
      combustible tobacco products, and in identifying novel biomarkers for tobacco
      smoke exposure and effect in the oral cavity.

PMID- 22960472
TI  - Placental transfer and metabolism: an overview of the experimental models
      utilizing human placental tissue.
AB  - Over the decades several ex vivo and in vitro models which utilize delivered
      human placenta have been developed to study various placental functions. The use
      of models originating from human placenta to study transplacental transfer and
      related mechanisms is an attractive option because human placenta is relatively
      easily available for experimental studies. After delivery placenta has served its
      purpose and is usually disposed of. The purpose of this review is to give an
      overview of the use of human placental models for the studies on human placental
      transfer and related mechanisms such as transporter functions and xenobiotic
      metabolism. Human placental perfusion, the most commonly used continuous cell
      lines, primary cells and tissue culture, as well as subcellular fractions are
      briefly introduced and their major advantages and disadvantages are discussed.

PMID- 22960473
TI  - The roles of BECN1 and autophagy in cancer are context dependent.
AB  - Malignant tissue contains a rare population of multi-potent cells known as cancer
      stem-like cells (CSCs). Autophagy is an important mechanism in cancer cell
      survival and tumor growth; it can both suppress malignant transformation and
      promote the growth of established cancers. However, the molecular mechanisms
      underlying the tumor-promoting and tumor-suppressing functions of autophagy in
      CSCs are not understood. Our work demonstrates that a prosurvival autophagic
      pathway is critical for breast CSC maintenance. Notably, we provide new evidence
      for the existence of two separate, context-dependent, autophagic programs that
      are regulated in opposite ways by BECN1.

PMID- 22960475
TI  - Epidemiology of chronic kidney disease among older adults: a focus on the oldest
      old.
AB  - The National Kidney Foundation (NKF), Kidney Disease Outcomes Quality Initiative
      (KDOQI) Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation,
      Classification, and Stratification expanded the focus of chronic kidney disease
      (CKD) management from end-stage renal disease (ESRD) to the entire spectrum of
      kidney disease including early kidney damage through the stages of kidney disease
      to kidney failure. A consequence of these guidelines is that a large number of
      older adults are being identified as having CKD, many of whom will not progress
      to ESRD. Concerns have been raised that reduced estimated glomerular filtration
      rate (eGFR) among older adults may not represent "disease" and using age-specific
      cut-points for staging CKD has been proposed. This implies that among older
      adults, CKD, as currently defined, may be benign. Several recent studies have
      shown that among people greater than or equal to 80 years old, CKD is associated
      with an increased risk for concurrent complications of CKD (eg, anemia, acidosis)
      and adverse outcomes including mortality and cardiovascular disease (CVD).
      Further, among older adults, CKD is associated with problems not traditionally
      thought to be associated with kidney disease. These nondisease-specific outcomes
      include functional decline, cognitive impairment, and frailty. Future research
      studies are necessary to determine the impact of concurrent complications of CKD
      and nondisease-specific problems on mortality and functional decline, the
      longitudinal trajectories of CKD progression, and patient preferences among the
      oldest old with CKD.

PMID- 22960474
TI  - Sexual dimorphism: the aging kidney, involvement of nitric oxide deficiency, and
      angiotensin II overactivity.
AB  - Females develop less age-dependent loss of renal function, which may be in part
      due to cardiorenal protective effects of estrogens. The impact of androgen level
      on cardiovascular-renal health is controversial. Estrogen acts through multiple
      mechanisms, sometimes beneficial, sometimes damaging, which makes it difficult to
      predict the effect of hormone replacement therapy (HRT) in an aging population.
      Nitric oxide (NO) deficiency occurs in aging and contributes to age-dependent
      cardiovascular risk and kidney damage. The increased oxidative stress of aging
      has effects at multiple sites in the NO biosynthetic pathway to lower NO
      production/action. Loss of NO together with activated angiotensin promotes some
      of the decrements in cardiovascular-renal function seen with age, which may be
      related to actions of the sex steroids.

PMID- 22960476
TI  - Lipopolysaccharide-binding protein, a surrogate marker of microbial
      translocation, is associated with physical function in healthy older adults.
AB  - BACKGROUND: Physical function declines, and markers of inflammation increase with
      advancing age, even in healthy persons. Microbial translocation (MT) is the
      systemic exposure to mucosal surface microbes/microbial products without overt
      bacteremia and has been described in a number of pathologic conditions. We
      hypothesized that markers of MT, soluble CD14 (sCD14) and lipopolysaccharide
      (LPS) binding protein (LBP), may be a source of chronic inflammation in older
      persons and be associated with poorer physical function. METHODS: We assessed
      cross-sectional relationships among two plasma biomarkers of MT (sCD14 and LBP),
      physical function (hand grip strength, short physical performance battery [SPPB],
      gait speed, walking distance, and disability questionnaire), and biomarkers of
      inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), TNF-alpha soluble receptor 1 [TNFsR1]) in 59 older (60
      89 years), healthy (no evidence of acute or chronic illness) men and women.
      RESULTS: LBP was inversely correlated with SPPB score and grip strength (p = .02
      and p < .01, respectively) and positively correlated with CRP (p = 0.04) after
      adjusting for age, gender, and body mass index. sCD14 correlated with IL-6 (p =
      .01), TNF-alpha (p = .05), and TNFsR1 (p < .0001). Furthermore, the correlations
      between LBP and SPPB and grip strength remained significant after adjusting for
      each inflammatory biomarker. CONCLUSIONS: In healthy older individuals, LBP, a
      surrogate marker of MT, is associated with worse physical function and
      inflammation. Additional study is needed to determine whether MT is a marker for
      or a cause of inflammation and the associated functional impairments.

PMID- 22960477
TI  - Comprehensive care improves health outcomes among elderly Taiwanese patients with
      hip fracture.
AB  - BACKGROUND: Few studies have investigated the effects of care models that combine
      interdisciplinary care with nutrition consultation, depression management, and
      fall prevention in older persons with hip fracture. The purpose of this study was
      to compare the effects of a comprehensive care program with those of
      interdisciplinary care and usual care for elderly patients with hip fracture.
      METHODS: A randomized experimental trial was used to explore outcomes for 299
      elderly patients with hip fracture receiving three treatment care models:
      interdisciplinary care (n = 101), comprehensive care (n = 99), and usual care (n
      = 99). Interdisciplinary care included geriatric consultation, continuous
      rehabilitation, and discharge planning with post-hospital services. Comprehensive
      care consisted of interdisciplinary care plus nutrition consultation, depression
      management, and fall prevention. Usual care included only in-hospital
      rehabilitation without geriatric consultation, in-home rehabilitation, and home
      environmental assessment. RESULTS: Participants in the comprehensive care group
      had better self-care ability (odds ratio, OR = 3.19, p < .01) and less risk of
      depression (OR = 0.48, p < .01) than those who received usual care. The
      comprehensive care group had less risk of depression (OR = 0.51, p < .05) and of
      malnutrition (OR = 0.48, p < .05) than the interdisciplinary care group during
      the first year following discharge. Older persons with hip fracture benefitted
      more from the comprehensive care program than from interdisciplinary care and
      usual care. CONCLUSIONS: Older persons with hip fracture benefitted more from
      comprehensive care including interdisciplinary care and nutrition consultation,
      depression management, and fall prevention than simply interdisciplinary care.

PMID- 22960478
TI  - UK experience in the monitoring and control of lead in drinking water.
AB  - At the zonal scale (e.g. a city or town), random daytime (RDT) sampling succeeded
      in demonstrating both the need for corrective action and the benefits of
      optimised orthophosphate dosing for plumbosolvency control, despite initial
      concerns about sampling reproducibility. Stagnation sampling techniques were
      found to be less successful. Optimised treatment measures to minimise lead in
      drinking water, comprising orthophosphate at an optimum dose and at an
      appropriate pH, have succeeded in raising compliance with the future European
      Union (EU) lead standard of 10 MUg/L from 80.4% in 1989-94 to 99.0% in 2010
      across England and Wales, with compliance greater than 99.5% in some regions.
      There may be scope to achieve 99.8% compliance with 10 MUg/L by further
      optimisation coupled to selective lead pipe removal, without widespread lead pipe
      removal. It is unlikely that optimised corrosion control, that includes the
      dosing of orthophosphate, will be capable of achieving a standard much lower than
      10 MUg/L for lead in drinking water. The experience gained in the UK provides an
      important reference for any other country or region that is considering its
      options for minimising lead in their drinking water supplies.

PMID- 22960479
TI  - Holy springs and holy water: underestimated sources of illness?
AB  - Use of holy springs and holy water is inherent in religious activities. Holy
      spring water is also used extensively for personal drinking water, although not
      assessed according to drinking water standards. Holy water in churches and
      chapels may cause infections via wetting of lips and sprinkling on persons. Our
      aim was to assess the microbiological and chemical water quality of holy springs
      and holy water in churches and hospital chapels. Of the holy springs
      investigated, only 14% met the microbiological and chemical requirements of
      national drinking water regulations. Considering results from sanitary
      inspections of the water catchments, no spring was assessed as a reliable
      drinking water source. All holy water samples from churches and hospital chapels
      showed extremely high concentrations of HPC; fecal indicators, Pseudomonas
      aeruginosa and Staphylococcus aureus occurred only in the most frequently visited
      churches. We conclude that it is highly necessary to include holy springs in
      programs for assessment and management of water quality. Public awareness has to
      be raised to perceive holy springs as potential sources of illness. Holy water
      can be another source of infection, especially in hospital chapels and frequently
      visited churches. Recommendations are made for proper water quality management of
      both water types.

PMID- 22960480
TI  - Estimation of pathogen concentrations in a drinking water source using
      hydrodynamic modelling and microbial source tracking.
AB  - The faecal contamination of drinking water sources can lead to waterborne disease
      outbreaks. To estimate a potential risk for waterborne infections caused by
      faecal contamination of drinking water sources, knowledge of the pathogen
      concentrations in raw water is required. We suggest a novel approach to estimate
      pathogen concentrations in a drinking water source by using microbial source
      tracking data and fate and transport modelling. First, the pathogen (norovirus,
      Cryptosporidium, Escherichia coli O157/H7) concentrations in faecal contamination
      sources around the drinking water source Lake Radasjon in Sweden were estimated
      for endemic and epidemic conditions using measured concentrations of faecal
      indicators (E. coli and Bacteroidales genetic markers). Afterwards, the fate and
      transport of pathogens within the lake were simulated using a three-dimensional
      coupled hydrodynamic and microbiological model. This approach provided
      information on the contribution from different contamination sources to the
      pathogen concentrations at the water intake of a drinking water treatment plant.
      This approach addresses the limitations of monitoring and provides data for
      quantitative microbial risk assessment (QMRA) and risk management in the context
      of faecal contamination of surface drinking water sources.

PMID- 22960481
TI  - Inactivation of Escherichia coli in water by pulsed dielectric barrier discharge
      in coaxial reactor.
AB  - An experimental study of ATCC (American Type Culture Collection) 8739 Escherichia
      coli bacteria inactivation in water by means of pulsed dielectric barrier
      discharge (PDBD) atmospheric pressure plasmas is presented. Plasma is generated
      by an adjustable power source capable of supplying high voltage 25 kV pulses, ~30
      MUs long and at a 500 Hz frequency. The process was conducted in a ~152 cm(3)
      cylindrical stainless steel coaxial reactor, endowed with a straight central
      electrode and a gas inlet. The bacterial concentration in water was varied from
      10(3) up to 10(8) E. coli cells per millilitre. The inactivation was achieved
      without gas flow in the order of 82% at 10(8) colony-forming units per millilitre
      (CFU mL(-1)) concentrations in 600 s. In addition, oxygen was added to the gas
      supply in order to increase the ozone content in the process, raising the
      inactivation percentage to the order of 90% in the same treatment time. In order
      to reach a higher efficiency however, oxygen injection modulation is applied,
      leading to inactivation percentages above 99.99%. These results are similarly
      valid for lower bacterial concentrations.

PMID- 22960482
TI  - Municipal wastewater treatment plants as pathogen removal systems and as a
      contamination source of noroviruses and Enterococcus faecalis.
AB  - Municipal wastewater treatment plants play a crucial role in reducing the
      microbial and pathogen load of human wastes before the end-products are
      discharged to surface waters (final effluent) or land spread (biosolids). This
      study investigated the occurrence frequency of noroviruses, Enterococcus faecalis
      and Enterococcus faecium in influent, final effluent and biosolids from four
      secondary wastewater treatment plants in northwestern Ireland (plants A-D) and
      observed the seasonal and spatial variation of the plant treatment efficiencies
      in the pathogen removals. It was noted that norovirus genogroup II was more
      resistant to the treatment processes than the norovirus genogroup I and other
      active viral particles, especially those in the discharge effluents. The
      percolating biofilm system at plant D resulted in better effluent quality than in
      the extended aerated activated sludge systems (plants A and B); primary biosolids
      produced at plant D may pose a higher health risk to the locals. The spread of
      norovirus genogroup II into the environment, irrespective of the wastewater
      treatment process, coincides with its national clinical predominance over
      norovirus genogroup I. This study provides important evidence that municipal
      wastewater treatment plants not only achieve pathogen removal but can also be the
      source of environmental pathogen contamination.

PMID- 22960483
TI  - The photodynamic inactivation of Staphylococcus aureus in water using visible
      light with a new expanded porphyrin.
AB  - In this work, the results of the application of organic expanded porphyrins in
      the disinfection of water by the photodynamic inactivation (PDI) technique are
      presented. The photoinactivation properties of a novel, expanded porphyrin,
      namely 20-(4-carboxyphenyl)-2,13-dimethyl-3,12-diethyl-(22pi) pentaphyrin
      (PCCox), were tested in the disinfection of water using Staphylococcus aureus as
      a Gram-positive bacteria model. The data showed that PCCox was effective against
      S. aureus bacteria at nanomolar concentrations. The variation with irradiation
      time and concentration was studied using both a multi-LED monochromatic light
      (lambda = 470 nm) and an incandescent light bulb with a wide emission spectrum. A
      PCCox dosage of 5 MUM was sufficient to achieve a 99.997% abatement of S. aureus
      within 1 h of 40 W/m(2) irradiation with monochromatic light (lambda = 470 nm),
      whereas under the same conditions using irradiation with white light, the
      abatement was 99.9997%.

PMID- 22960484
TI  - Survival of human pathogenic bacteria in different types of natural mineral
      water.
AB  - The aim of this study was to determine the survival of human pathogens
      (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) in five
      natural mineral waters (NMWs) with different properties and mineralization
      levels. Five NMWs from four Spanish spas with different dry residue at 110 
      degrees C were used: A = 76,935 mg/L; B = 1,827 mg/L; C = 808.4 mg/L; D = 283.8
      mg/L; and E = 170.4 mg/L. An initial inoculum of 1 * 10(6) colony forming units
      (cfu)/mL was used for survival studies. Distilled water, chlorinated tap water
      and Mueller-Hinton broth were used as controls. Colony counts in all different
      waters were lower than those achieved with Mueller-Hinton broth over all
      incubation periods. A direct effect between the bacterial survival and the level
      of mineralization water was observed. The NMW E with low mineralization level
      along with the radioactive properties showed the highest antibacterial activity
      among all NMWs.

PMID- 22960485
TI  - Decontamination of a drinking water pipeline system contaminated with adenovirus
      and Escherichia coli utilizing peracetic acid and chlorine.
AB  - A contaminated drinking water distribution network can be responsible for major
      outbreaks of infections. In this study, two chemical decontaminants, peracetic
      acid (PAA) and chlorine, were used to test how a laboratory-scale pipeline system
      can be cleaned after simultaneous contamination with human adenovirus 40 (AdV40)
      and Escherichia coli. In addition, the effect of the decontaminants on biofilms
      was followed as heterotrophic plate counts (HPC) and total cell counts (TCC).
      Real-time quantitative polymerase chain reaction (qPCR) was used to determine
      AdV40 and plate counting was used to enumerate E. coli. PAA and chlorine proved
      to be effective decontaminants since they decreased the levels of AdV40 and E.
      coli to below method detection limits in both water and biofilms. However,
      without decontamination, AdV40 remained present in the pipelines for up to 4
      days. In contrast, the concentration of cultivable E. coli decreased rapidly in
      the control pipelines, implying that E. coli may be an inadequate indicator for
      the presence of viral pathogens. Biofilms responded to the decontaminants by
      decreased HPCs while TCC remained stable. This indicates that the mechanism of
      pipeline decontamination by chlorine and PAA is inactivation rather than physical
      removal of microbes.

PMID- 22960486
TI  - Comparison of enterovirus and adenovirus concentration and enumeration methods in
      seawater from Southern California, USA and Baja Malibu, Mexico.
AB  - Despite being important etiological agents of waterborne illness, the sources,
      transport and decay of human viruses in recreational waters are not well
      understood. This study examines enterovirus and adenovirus concentrations in
      coastal water samples collected from four beaches impacted by microbial
      pollution: (1) Malibu Lagoon, Malibu; (2) Tijuana River, Imperial Beach; (3) Baja
      Malibu, Baja California; and (4) Punta Bandera, Baja California. Water samples
      were concentrated using a flocculation-based skim milk method and dead-end
      membrane filtration (MF). Viruses were enumerated using cell culture infectivity
      assays and reverse transcription quantitative polymerase chain reaction (RT
      QPCR). Across concentration and quantification methods, enteroviruses were
      detected more often than adenoviruses. For both viruses, MF followed by (RT)QPCR
      yielded higher concentrations than skim milk flocculation followed by (RT)QPCR or
      cell culture assays. Samples concentrated by skim milk flocculation and
      enumerated by (RT)QPCR agreed more closely with concentrations enumerated by cell
      culture assays than MF followed by (RT)QPCR. The detection of viruses by MF and
      (RT)QPCR was positively correlated with the presence of infectious viruses.
      Further research is needed to determine if detection of viruses by rapid methods
      such as (RT)QPCR can be a useful water quality monitoring tool to assess health
      risks in recreational waters.

PMID- 22960487
TI  - Survey and genetic characterization of wastewater in Tunisia for Cryptosporidium
      spp., Giardia duodenalis, Enterocytozoon bieneusi, Cyclospora cayetanensis and
      Eimeria spp.
AB  - The microbial diversity of wastewater used for irrigation and fertilization was
      assessed using specific polymerase chain reaction (PCR) assays to detect and
      genotype several pathogenic protists including Cryptosporidium spp., Giardia
      duodenalis, Cyclospora spp., Eimeria spp. and Enterocytozoon bieneusi. A total of
      220 wastewater samples (110 raw, 110 treated) and 12 sludge samples were
      collected from 2005 to 2008 from 18 treatment plants located throughout Tunisia.
      Except for Cyclospora, which was detected only once, E. bieneusi (61%), G.
      duodenalis (28%), Cryptosporidium spp. (27%) and Eimeria spp. (45%) were
      frequently observed in wastewater and sludge. Sequencing of PCR products showed
      that C. hominis, C. andersoni, G. duodenalis sub-assemblage A-II and E. bieneusi
      genotypes D and IV were the most prevalent. An analysis of the distribution of
      209 internal transcribed spacer sequences of E. bieneusi originating from
      wastewater at the 18 treatment plants showed a similar genetic diversity,
      regardless of the geographical location. The identification of these parasite
      species and genotypes and of host-specific Eimeria species indicates that the
      microbial quality of wastewater was impacted by humans, livestock and rodents.
      Given the public health risks that some of these parasites represent, guidelines
      on wastewater usage are needed to minimize human exposure to these pathogens.

PMID- 22960488
TI  - Surveillance of human and swine adenovirus, human norovirus and swine circovirus
      in water samples in Santa Catarina, Brazil.
AB  - Animal and human wastewater can potentially contaminate water sources and the
      treatment of drinking water may not effectively remove all contaminants,
      especially viruses. The purpose of the present study was to evaluate the viral
      contamination of water used for human and animal consumption in the city of
      Concordia, located in southern Brazil. Porcine circovirus type 2 (PCV2), porcine
      adenovirus (PAdV), human adenovirus (HAdV) and human norovirus (NoV) were
      searched for using quantitative polymerase chain reaction (qPCR). HAdV-positive
      samples were tested for viral infectivity by plaque assay. The qPCR results
      showed that PAdV, PCV2 and HAdV genetic material were present in all sampling
      sites. NoV was absent in all samples. The presence of genetic material from PAdV
      and PCV2 was detected in 30% and 45% of the 36 analyzed samples, respectively,
      with an average of 10(2) gc mL(-1) for PAdV and 10(4) gc mL(-1) for PCV2. HAdV
      was present in 100% of the samples, with an average of 10(4) gc mL(-1). However,
      in plaque assay, only 36% of the samples were positive. As viable particles of
      HAdV were found in drinking water, these results confirm that swine manure and
      human sewage impact surface water and groundwater, endangering water quality and
      indicating a potential risk to public health.

PMID- 22960489
TI  - Investigation of water consumption patterns among Irish adults for waterborne
      quantitative microbial risk assessment (QMRA).
AB  - Microbial and chemical contamination of drinking water supplies can cause human
      health problems. Microbial pathogens are of primary concern and quantitative
      microbial risk assessment (QMRA) is employed to assess and manage the risks they
      pose. Estimates of drinking water consumption, or distributions, are required to
      assess levels of waterborne pathogen exposure. To establish distributions for the
      Irish population, water consumption data were collected from 549 rural survey
      respondents. A further 110 participants completed a five-day water consumption
      diary. Average daily consumption of tap-water among the primarily rural-dwelling
      questionnaire respondents was 940 ml day(-1) (SD 670 ml day(-1)) and 1,186 ml
      day(-1) (SD 701 ml day(-1)) among the principally urban-dwelling diary
      respondents. Both mean figures are significantly less than the 2,000 ml day(-1)
      default figure currently used for QRMA; therefore its use may lead to
      overestimation of the waterborne health burden. As the observed daily consumption
      difference between rural and urban residents is statistically significant, use of
      separate consumption distributions for QMRA is advocated. Although males reported
      higher daily tap-water consumption rates than females, these differences were
      insignificant, so separate consumption distributions are not considered
      necessary. A log-normal distribution provides the most adequate fit for daily tap
      water intake (ml day(-1)) within both datasets.

PMID- 22960490
TI  - The bacteriological quality of drinking water in Haldwani block of Nainital
      district, Uttarakhand, India.
AB  - A cross-sectional study was conducted to assess the bacteriological quality of
      water in Haldwani block, Nainital District, India. Stratified random sampling was
      used to categorize water sources and consumer points. In total, 108 samples were
      collected: 15 from the Gola river, 51 from water taps, 24 from water treatment
      plants and 18 from tube wells. Samples were tested for coliforms by the most
      probable number technique. Identification of species was done by standard
      procedures. Of 108 water samples, 58.8% were found to be polluted. All samples of
      water (n = 15) from different sites of the Gola river were found to be highly
      contaminated. Out of 24 water treatment plant samples, four samples were found
      unsatisfactory, while more than half (51.6%) of its supplies to water taps were
      polluted. From tube wells and their water taps, 88.8 and 60% samples were found
      safe for drinking respectively. Bacterial contamination of water treatment plants
      and their supplies indicates significant disparities in the efficiency of water
      treatment processes. Contamination of water taps of tube wells suggests leakage
      of pipes. There is an urgent need to improve these services to ensure the supply
      of safe water for consumers.

PMID- 22960491
TI  - Opportunistic pathogens and faecal indicators in drinking water associated
      biofilms in Cluj, Romania.
AB  - Biofouling occurs without exception in all water systems, with undesirable
      effects such as biocorrosion and deterioration of water quality. Drinking water
      associated biofilms represent a potential risk to human health by harbouring
      pathogenic or toxin-releasing microorganisms. This is the first study
      investigating the attached microbiota, with potential threat to human health, in
      a public water system in Romania. The presence and the seasonal variation of
      viable faecal indicators and opportunistic pathogens were investigated within
      naturally developed biofilms in a drinking water treatment plant. Bacterial
      frequencies were correlated with microbial loads in biofilms as well as with
      physical and chemical characteristics of biofilms and raw water. The biofilms
      assessed in the current study proved to be extremely active microbial consortia.
      High bacterial numbers were recovered by cultivation, including Pseudomonas
      aeruginosa, Escherichia coli, Aeromonas hydrophila, intestinal enterococci and
      Clostridium perfringens. There were no Legionella spp. detected in any biofilm
      sample. Emergence of opportunistic pathogens in biofilms was not significantly
      affected by the surface material, but by the treatment process. Implementation of
      a water safety plan encompassing measures to prevent microbial contamination and
      to control biofouling would be appropriate.

PMID- 22960492
TI  - Waterborne transmission of Giardia and Cryptosporidium at river beaches in
      Southern Europe (Portugal).
AB  - Giardia and Cryptosporidium are the most frequent enteric protozoa causing
      gastroenteritis in humans worldwide. Intense recreational activity at Portuguese
      river beaches triggered the opportunity for a 2-year seasonal survey of 19 large
      river basin beaches. A total of 74 samples were collected and processed according
      to USEPA Method 1623 to detect Cryptosporidium and Giardia (oo)cysts. Faecal
      indicators (thermotolerant/total coliforms, Escherichia coli, and enterococci)
      and physicochemical parameters were also analysed according to the EU Bath Water
      Directive (BWD). Results pointed to a widespread presence of these protozoa at
      Portuguese river beaches. The percentage of samples testing positive for Giardia
      and Cryptosporidium were 85 and 82% respectively, with no significant differences
      between wet and dry seasons (p > 0.05). Although Portuguese river beaches present
      a very low exposure risk for infection with Giardia and Cryptosporidium (under
      10(-3)), a few particular cases revealed values over 0.2%, and were related to
      stormy wet events. The correlation between levels of Giardia and thermotolerant
      coliforms, E. coli and enterococci, was high (r >= 0.87, p < 0.001), suggesting
      the need to carry out specific procedures for the detection of Giardia and
      Cryptosporidium whenever the values of those faecal indicators approach the
      maximum allowed level of the EU BWD.

PMID- 22960494
TI  - Reinforcement learning for discounted values often loses the goal in the
      application to animal learning.
AB  - The impulsive preference of an animal for an immediate reward implies that it
      might subjectively discount the value of potential future outcomes. A theoretical
      framework to maximize the discounted subjective value has been established in the
      reinforcement learning theory. The framework has been successfully applied in
      engineering. However, this study identified a limitation when applied to animal
      behavior, where in some cases, there is no learning goal. Here a possible
      learning framework was proposed that is well-posed in any cases and that is
      consistent with the impulsive preference.

PMID- 22960495
TI  - Impact of rotavirus vaccination in regions with low and moderate vaccine uptake
      in Germany.
AB  - In Germany, routine RV-vaccination is not adopted into the national immunization
      schedule as of 2012. Because RV-vaccines were already on the market since 2006,
      in 2010 a moderate (58%) and low (22%) vaccine uptake was observed in the 5
      eastern federal states (EFS) and the 11 western federal states (WFS),
      respectively. To assess the impact of RV-vaccination, we compared the incidence
      rates (IR) of RV-related hospitalizations before (2004-2006) and in seasons after
      (2008/09-2010/11) RV-vaccine introduction in Germany by utilizing data from the
      national mandatory disease reporting system. In the EFS, the IR was significantly
      reduced in age-groups < 18 mo in 2008/09 and in age-groups < 24 mo in 2009/10
      2010/11. In the WFS an IR-reduction was observed only in age-groups < 12 mo in
      2008/09 and in age-groups < 18 mo in 2009/10-2010/11. Overall IR-reduction in age
      groups < 24 mo comparing 2008-11 with 2004-06 was 36% and 25% in EFS and WFS,
      respectively. In addition, we computed IR-ratios (IRR) in the seasons after mid
      2006 with negative binomial regression. The effect of vaccination was independent
      from the geographic region. Vaccination was associated with a significant
      reduction in RV-related hospitalizations in the age-groups 6-23 mo. Most
      prominently, vaccination of 50% of infants led to an estimated decrease in age
      group 6-11 mo by 42%. No significant reduction was observed in age-groups >= 24
      mo. In conclusion, in the German setting with low to moderate vaccine uptake, RV
      related hospitalization incidence decreased substantially depending on the
      achieved vaccination coverage, but only in the first two years of life.

PMID- 22960497
TI  - Neuromuscular diseases account for a major burden in the field of neurological
      diseases in the wealthy part of the world.

PMID- 22960496
TI  - Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1
      CN54gp140 effectively primes mucosal boost inoculations.
AB  - Dissolving polymeric microneedle arrays formulated to contain recombinant CN54
      HIVgp140 and the TLR4 agonist adjuvant MPLA were assessed for their ability to
      elicit antigen-specific immunity. Using this novel microneedle system we
      successfully primed antigen-specific responses that were further boosted by an
      intranasal mucosal inoculation to elicit significant antigen-specific immunity.
      This prime-boost modality generated similar serum and mucosal gp140-specific IgG
      levels to the adjuvanted and systemic subcutaneous inoculations. While the
      microneedle primed groups demonstrated a balanced Th1/Th2 profile, strong Th2
      polarization was observed in the subcutaneous inoculation group, likely due to
      the high level of IL-5 secretion from cells in this group. Significantly, the
      animals that received a microneedle prime and intranasal boost regimen elicited a
      high level IgA response in both the serum and mucosa, which was greatly enhanced
      over the subcutaneous group. The splenocytes from this inoculation group secreted
      moderate levels of IL-5 and IL-10 as well as high amounts of IL-2, cytokines
      known to act in synergy to induce IgA. This work opens up the possibility for
      microneedle-based HIV vaccination strategies that, once fully developed, will
      greatly reduce risk for vaccinators and patients, with those in the developing
      world set to benefit most.

PMID- 22960498
TI  - Current world literature.

PMID- 22960500
TI  - Clinical and molecular analysis of isovaleric acidemia patients in the United
      Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD
      gene.
AB  - Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine
      metabolism caused by deficiency of mitochondrial isovaleryl-CoA dehydrogenase
      (IVD). Accumulation of isovaleryl-CoA derivatives to toxic levels results in
      clinical symptoms of the disease. Here, we investigate the clinical and molecular
      features of Arab patients with IVA. Patients from five unrelated families were
      evaluated clinically and for defects in the IVD gene. Four novel mutations
      (p.F382fs, p.R392H, p.R395Q and p.E408K) have been identified with p.R395Q
      occurring in two families. In addition, molecular modeling of the identified
      missense mutations predicted their damaging effects on the protein and
      computational analysis of the p.F382fs mutation predicted the disruption of a 3'
      splicing site resulting in inactive or unstable gene product. Furthermore, we
      found an unusual case of a 17 years old female homozygous for the p.R392H
      mutation with no clinical symptoms. Our results illustrate a heterogeneous
      mutation spectrum and clinical presentation in the relatively small UAE
      population.

PMID- 22960501
TI  - Cyclodextrin as membrane protectant in spray-drying and freeze-drying of
      PEGylated liposomes.
AB  - In this study it was investigated whether hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) is able to stabilize the liposomal membranes during drying of long
      circulating polyethylene glycol (PEG) coated liposomes, as compared to the
      disaccharides trehalose and sucrose. PEGylated liposomes loaded with prednisolone
      disodium phosphate (PLP) were dried by spray-drying or freeze-drying. The dried
      powders were tested on their residual moisture content, glass transition
      temperature and amorphous character. Upon reconstitution the liposomal size, size
      distribution and drug retention were determined and the results were compared to
      the characteristics of the formulation solution before drying. In contrast to the
      disaccharides, HPbetaCD stabilizes the liposomal membranes of the PEGylated
      liposomes during the drying process of both spray drying and freeze-drying when
      present in a lipid:carbohydrate ratio of 1:6 (w/w). The resulting powder can be
      stored at room temperature. No changes in size and size distribution were seen
      upon reconstitution of the HPbetaCD containing formulations. Drying resulted in a
      minimal leaking of PLP from the liposomes. Its relatively high  [Formula: see
      text]  and T(g) of HPbetaCD, as compared to the disaccharides, make HPbetaCD an
      excellent membrane protectant for dry PEGylated liposomal formulations.

PMID- 22960502
TI  - Impurity profiling of trandolapril under stress testing: Structure elucidation of
      by-products and development of degradation pathway.
AB  - Various regulatory authorities like International Conference on Harmonization
      (ICH), US Food and Drug Administration, Canadian Drug and Health Agency are
      emphasizing on the purity requirements and the identification of impurities in
      active pharmaceutical drugs. Qualification of the impurities is the process of
      acquiring and evaluating data that establishes biological safety of an individual
      impurity; thus, revealing the need and scope of impurity profiling of drugs in
      pharmaceutical research. As no stability-indicating method is available for
      identification of degradation products of trandolapril, a new angiotensin
      converting enzyme inhibitor (ACEI), under stress testing, the development of an
      accurate method is needed for quantification and qualification of degradation
      products. Ultra high performance liquid chromatography (UPLC) coupled to
      electrospray tandem mass spectrometry was used for the rapid and simultaneous
      analysis of trandolapril and its degradation products. Chromatographic separation
      was achieved in less than 4 min, with improved peak resolution and sensitivity.
      Thanks to this method, the kinetics of trandolapril degradation under various
      operating conditions and the characterization of the structure of the by-products
      formed during stress testing have been determined. Thereafter, a mechanism of
      trandolapril degradation in acid and neutral conditions, including all the
      identified products, was then proposed.

PMID- 22960503
TI  - Preactivated thiomers: permeation enhancing properties.
AB  - The study was aimed to prepare a series of poly(acrylic acid)-cysteine-2
      mercaptonicotinic acid conjugates (preactivated thiomers) and to evaluate the
      influence of molecular mass or degree of preactivation with 2-mercaptonicotinic
      acid (2MNA) on their permeation enhancing properties. Preactivated thiomers with
      different molecular mass and different degree of preactivation were synthesized
      and categorized on the basis of their molecular mass and degree of preactivation
      as PAA(100)-Cys-2MNA (h), PAA(250)-Cys-2MNA (h), PAA(450)-Cys-2MNA (h), PAA(450)
      Cys-2MNA (m) and PAA(450)-Cys-2MNA (l). In vitro permeation studies, the
      permeation enhancement ability for preactivated thiomers was ranked as PAA(450)
      Cys-2MNA (h)>PAA(250)-Cys-2MNA (h)>PAA(100)-Cys-2MNA (h) on both Caco-2 cell
      monolayers and rat intestinal mucosa. Comparing the influence of degree of
      preactivation with 2MNA on permeation enhancement, the following order PAA(450)
      Cys-2MNA (h)>PAA(450)-Cys-2MNA (m)~PAA(450)-Cys-2MNA (l) on Caco-2 cell
      monolayers and PAA(450)-Cys-2MNA (m)>PAA(450)-Cys-2MNA (h)>PAA(450)-Cys-2MNA (l)
      on intestinal mucosa was observed. The P(app) of sodium fluorescein was 5.08-fold
      improved on Caco-2 cell monolayers for PAA(450)-Cys-2MNA (h) and 2.46-fold
      improved on intestinal mucosa for PAA(450)-Cys-2MNA (m), respectively, in
      comparison to sodium fluorescein in buffer only. These results indicated that
      preactivated thiomers could be considered as a promising macromolecular
      permeation enhancing polymer for non-invasive drug administration.

PMID- 22960505
TI  - Estimating the toxicity of the weak base carbendazim to the earthworm (Eisenia
      fetida) using in situ pore water concentrations in different soils.
AB  - Both sorption by soil and uptake by organisms of ionizable organic pollutants
      depend on their speciation (i.e., neutral and ionized forms); thus, the
      bioavailability of ionizable organic pollutants is more complicated than that of
      neutral organic pollutants in soil. The toxicity of the weak base carbendazim to
      earthworms (Eisenia fetida) was estimated using Soxhlet extracted concentrations
      (C(SE)), an excess of water extracted concentrations (C(EEW)), ex situ pore water
      concentrations (C(EPW)) and in situ pore water concentrations (C(IPW)) in
      different soils. The results indicated that the median lethal concentrations
      (LC50) calculated from C(SE) ranged from 2.32 to 34.0 mg kg(-1) in the five
      tested soils and the coefficient of variation (CV) of LC50s was 69.8%. When the
      LC50 was calculated from the C(EEW), C(EPW) and C(IPW), the variability of the
      LC50 gradually became smaller in these soils, with the CVs of LC50s being 58.1%,
      50.6% and 38.6% (for C(EEW), C(EPW) and C(IPW), respectively). However, the LC50
      based on C(IPW) in strongly acidic soil (where carbendazim partially exists as
      ionized form) was significantly lower than in other soils, and the values of the
      LC50 calculated from the in situ pore water concentrations were approximately
      equal. The results indicated that the in situ pore water concentration could be
      used to estimate the toxicity of carbendazim in different soils especially in
      those soils where carbendazim exists in the neutral form.

PMID- 22960506
TI  - Size distribution of EC, OC and particle-phase PAHs emissions from a diesel
      engine fueled with three fuels.
AB  - The size distribution of elemental carbon (EC), organic carbon (OC) and particle
      phase PAHs emission from a direct injection diesel engine fueled with a waste
      cooking biodiesel, ultra low sulfur diesel (ULSD, 10-ppm-wt), and low sulfur
      diesel (LSD, 400-ppm-wt) were investigated experimentally. The emission factor of
      biodiesel EC is 90.6 mg/kh, which decreases by 60.3 and 71.7%, compared with ULSD
      and LSD respectively and the mass mean diameter (MMD) of EC was also decreased
      with the use of biodiesel. The effect of biodiesel on OC emission might depend on
      the engine operation condition, and the difference in OC size distribution is not
      that significant among the three fuels. For biodiesel, its brake specific
      emission of particle-phase PAHs is obviously smaller than that from the two
      diesel fuels, and the reduction effect appears in almost all size ranges. In
      terms of size distribution, the MMD of PAHs from biodiesel is larger than that
      from the two diesel fuels, which could be attributed to the more effective
      reduction on combustion derived PAHs in nuclei mode. The toxicity analysis
      indicates that biodiesel could reduce the total PAHs emissions, as well as the
      carcinogenic potency of particle-phase PAHs in almost all the size ranges.

PMID- 22960504
TI  - Isolation of Chlamydia trachomatis and membrane vesicles derived from host and
      bacteria.
AB  - The study of intracellular bacteria and nanometer-size membrane vesicles within
      infected host cells poses an important challenge as it is difficult to identify
      each distinct population in the context of the complex populations generated from
      active host-pathogen interactions. Here, suspension cultures of L929 cells
      infected with the prevalent obligate intracellular bacterium Chlamydia
      trachomatis strain F/Cal-IC-13 are utilized for the large scale preparation and
      isolation of natural membrane vesicles and bacterial forms. Cell lysis with
      nitrogen cavitation in combination with differential centrifugation, OptiPrepTM
      density gradient separation, and immunoenrichment using anti-chlamydial
      lipopolysaccharide antibodies and MagnaBind beads allows for the isolation of
      both productive and persistent bacterial forms, as well as membrane vesicles
      derived from the host and pathogen. We have evaluated these populations by
      electron microscopy and Western blot analysis for identification of biomarkers.
      In addition, purified persistent forms of C. trachomatis induced by ampicillin
      display adenosine-5'-triphosphate (ATP) transport activity, suggesting that
      ampicillin-induced persistent C. trachomatis organisms, at least in part, rely
      upon host ATP as an energy source. Importantly, several chlamydial cytotoxic
      and/or secreted proteins are demonstrated to be associated with these vesicles,
      supporting the idea that membrane vesicles are generated by Chlamydia as a means
      of carrying and delivering virulence factors necessary for pathogenesis. The
      ability to produce large-scale infections and generate distinct bacteria and host
      derived populations for biochemical analysis, while reducing the burdens of time
      and cost have implications in all areas of chlamydiology. These protocols can be
      applied to other strains of C. trachomatis or other intracellular bacteria.

PMID- 22960507
TI  - How ignoring physiological noise can bias the conclusions from fMRI simulation
      results.
AB  - Neuroimaging researchers use simulation studies to validate their statistical
      methods because it is acknowledged that this is the most feasible way to know the
      ground truth of the data. The noise model used in these studies typically varies
      from a simple Gaussian distribution to an estimate of the noise distribution from
      real data. However, although several studies point out the presence of
      physiological noise in fMRI data, this noise source is currently lacking in
      simulation studies. Therefore, we explored the impact of adding physiological
      noise to the simulated data. For several experimental designs, fMRI data were
      generated under different noise models while the signal-to-noise ratio was kept
      constant. The sensitivity and specificity of a standard statistical parametric
      mapping (SPM) analysis were determined by comparing the known activation with the
      detected activation. We show that by including physiological noise in the data
      generation process, the simulation results in terms of sensitivity and
      specificity drop dramatically. Additionally, we used the new proposed simulation
      model to compare a standard SPM analysis against the method proposed by Cabella
      et al. (2009). The results indicate that the analysis of data containing no
      physiological noise yields a better performance of the SPM analysis. However, if
      physiological noise is included in the data, the sensitivity and specificity of
      the Cabella method are higher compared to the SPM analysis. Based on these
      results, we argue that the results of current simulation studies are likely to be
      biased, especially when analysis methods are compared using ROC curves.

PMID- 22960508
TI  - 2011 presidential address.

PMID- 22960509
TI  - Unyielding progress:  treatment paradigms for giant aneurysms.

PMID- 22960510
TI  - Red cerebral veins:  the science, the art, and the craft.

PMID- 22960511
TI  - Overcoming a bad outcome:  thoughts from a colleague.

PMID- 22960512
TI  - Seeking new solutions:  stimulation of diseased circuits in depression and other
      neurobehavioral disorders.

PMID- 22960513
TI  - Unyielding progress: carotid stenting cases from Millard Fillmore Gates Circle
      Hospital in Buffalo, New York.

PMID- 22960514
TI  - Seeking new paradigms in epilepsy:  stereotactic radiosurgery.

PMID- 22960515
TI  - Honoring our public responsibility:  creating milestone and matrix-based training
      in an era of duty hour restrictions.

PMID- 22960517
TI  - Does extent of resection of a glioblastoma matter?

PMID- 22960516
TI  - Adjuncts for maximizing resection: 5-aminolevuinic acid.

PMID- 22960518
TI  - Cervical spine arthroplasty:  fact or fiction:  the absence of need for
      arthroplasty.

PMID- 22960519
TI  - Cervical disk arthroplasty:  patient selection.

PMID- 22960520
TI  - An overview of domestic and international clinical trials for delivery of
      cellular therapies to the spinal cord.

PMID- 22960521
TI  - Results of a national neurosurgery resident survey on duty hour regulations.

PMID- 22960523
TI  - Peripheral neuromodulation for headache and craniofacial pain:  indications,
      outcomes, and complications from a single center.

PMID- 22960522
TI  - Canine model of convection-enhanced delivery of cetuximab-conjugated iron-oxide
      nanoparticles monitored with magnetic resonance imaging.

PMID- 22960524
TI  - Carotid recanalization in nonacute internal carotid artery occlusion:  a
      therapeutic option for ischemic stroke.

PMID- 22960525
TI  - Helmeted vs nonhelmeted: a retrospective review of outcomes from 2-wheeled
      vehicle accidents at a level 1 trauma center.

PMID- 22960537
TI  - Effect of proximal box elevation with resin composite on marginal quality of
      resin composite inlays in vitro.
AB  - OBJECTIVES: To evaluate marginal quality and resin-resin transition of lab made
      resin composite inlays in deep proximal cavities with and without 3 mm proximal
      box elevation (PBE) using resin composites before and after thermo-mechanical
      loading (TML). METHODS: MOD cavities with one proximal box beneath the
      cementoenamel junction were prepared in 40 extracted human third molars. Proximal
      boxes ending in dentine were elevated 3 mm with different resin composites (G
      Cem, Maxcem Elite as self-adhesive resin cements and Clearfil Majesty Posterior
      as restorative resin composite in one or three layers bonded with AdheSE), or
      left untreated. Clearfil Majesty Posterior inlays were luted with Syntac and
      Variolink II (n = 8). Marginal quality as well as the PBE-composite inlay
      interface was analyzed under an SEM using epoxy resin replicas before and after
      thermomechanical loading (100,000 * 50 N and 2500 thermocylces between +5 
      degrees C and +55  degrees C). RESULTS: Bonding resin composite inlays directly
      to dentine showed similar amounts of gap-free margins in dentine compared to PBE
      applied in three consecutive layers (p > 0.05). The groups with self-adhesive
      resin cements for PBE exhibited significantly more gaps in dentine (p < 0.05).
      SIGNIFICANCES: With layered resin composite, PBE is effective in indirect resin
      composite bonding to deep proximal boxes. Self-adhesive resin cements are not
      suitable for this indication.

PMID- 22960538
TI  - Disruption of enamel crystal formation quantified by synchrotron
      microdiffraction.
AB  - OBJECTIVES: To understand the pathology of the ultrastructure of enamel affected
      by systemic disorders which disrupt enamel tissue formation in order to give
      insight into the precise mechanisms of matrix-mediated biomineralization in
      dental enamel in health and disease. METHODS: Two-dimensional synchrotron X-ray
      diffraction has been utilized as a sophisticated and useful technique to
      spatially quantify preferred orientation in mineralized healthy deciduous dental
      enamel, and the disrupted crystallite organization in enamel affected by a
      systemic disease affecting bone and dental mineralization (mucopolysaccharidosis
      Type IVA and Type II are used as examples). The lattice spacing of the
      hydroxyapatite phase, the crystallite size and aspect ratio, and the quantified
      preferred orientation of crystallites across whole intact tooth sections, have
      been determined using synchrotron microdiffraction. RESULTS: Significant
      differences in mineral crystallite orientation distribution of affected enamel
      have been observed compared to healthy mineralized tissue. The gradation of
      enamel crystal orientation seen in healthy tissue is absent in the affected
      enamel, indicating a continual disruption in the crystallite alignment during
      mineral formation. CONCLUSIONS: This state of the art technique has the potential
      to provide a unique insight into the mechanisms leading to deranged enamel
      formation in a wide range of disease states. CLINICAL RELEVANCE: Characterising
      crystal orientation patterns and geometry in health and following disruption can
      be a powerful tool in advancing our overall understanding of mechanisms leading
      to the tissue phenotypes seen clinically. Findings can be used to inform the
      appropriate dental management of these tissues and/or to investigate the
      influence of therapeutic interventions or external stressors which may impact on
      amelogenesis.

PMID- 22960539
TI  - It takes two to tango: activation of cortex and lumbosacral circuitry restores
      locomotion in spinal cord injury.

PMID- 22960540
TI  - Surgical decompression after spinal cord injury: the earlier, the better!

PMID- 22960541
TI  - Is tracheal intubation possible during pediatric cardiopulmonary resuscitation
      without interruption of chest compressions? A simulation study.

PMID- 22960542
TI  - Prevalence of HBV infection in suspected population of conflict-affected area of
      war against terrorism in North Waziristan FATA Pakistan.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of severe liver
      diseases including fibrosis, hepatocellular carcinoma (HCC) and cirrhosis related
      end stage liver diseases (ESLD) in mankind. It is a common belief that infectious
      diseases have historically been responsible for the massiveness of war-related
      deaths, so the aim of this study was to estimate the prevalence of HBV infection
      and to demonstrate the various socio-economic, demographic and possible risk
      factors related to HBV infection among the conflict-affected peoples due to war
      against terrorism in North Waziristan. METHODS: Blood samples were collected from
      total 790 suspected individuals from the conflict-affected population of North
      Waziristan and were analyzed initially tested for the presence of HBsAg, HBeAg
      antigens, Anti-HBc and Anti-HBs antibodies using ELISA methods. All the positive
      samples were tested by real time PCR to confirm the presence of HBV DNA in ELISA
      positive specimens. RESULTS: Total of 126 (15.94%) samples were found positive
      for HBV DNA by real-time PCR. Among these positive subjects, 95 (75.5%) were
      males while 31 (24.5%) were females in a ratio of approximately 3:1. High HBV
      prevalence (41.26%) was observed among the subjects of subdivision Miran Shah
      relating to the high frequency of military activities against terrorism as
      compared to Mir Ali subdivision (35.7%) and Razmak subdivision (19.8%). Among the
      age groups, high prevalence (38.88%) was observed in age group 21-30 as compared
      to children and in older age groups. The modes of HBV transmission in this area
      was associated with re-uses of contaminated needles/syringes in medical care,
      barbers shops, sexual exposure and tattooing are the principal causal risks
      factors. Furthermore HBV infection was significantly higher in people with low
      socioeconomic status, in illiterate persons and in drivers. CONCLUSION: Our
      results indicate high prevalence rate of HBV infection in young subjects
      obviously confirms the entire absence of any program to fight HBV. Mass
      Immunization programs, awareness campaigns and education efforts should be
      practiced immediately to reduce HBV transmission among young peoples of this
      conflict zone.

PMID- 22960543
TI  - Topical treatment with Tong-Luo-San-Jie gel alleviates bone cancer pain in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The herbal analgesic gel Tong-Luo-San-Jie (TLSJ)
      and its modifications are used in traditional Chinese medicine to manage cancer
      pain. However, its mechanisms are still unknown. AIM OF THE STUDY: To investigate
      the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model.
      MATERIALS AND METHODS: A bone cancer pain rat model was established by
      inoculating Walker 256 rat carcinoma cells directly into the right tibial
      medullary cavity of Sprague-Dawley rats (150-170 g); Phosphate buffered saline
      (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated
      twice a day with external TLSJ gel (0.5 g/cm(2)/day) or inert gel control for 21
      day (n=10/group). Behavioral tests such as mechanical threshold and paw
      withdrawal latency (PWL) were carried out. Osteoclastic activities were
      determined and carboxyterminal pyridinoline cross-linked type I collagen
      telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations
      were detected with ELISA after treatment. Adverse effects were monitored, and
      biochemical and histological tests were performed in naive rats treated with
      local TLSJ gel for six weeks. RESULTS: TLSJ treatment significantly restored bone
      cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It
      also decreased the level of blood serum ICTP and BAP and inhibited osteoclast
      activities. No adverse effects or abnormal biochemical and histological changes
      were detected after TLSJ treatment. CONCLUSION: The present study shows that TLSJ
      significantly inhibits bone cancer-induced thermal and mechanical sensitization.
      It suggests that the gel may be useful in managing cancer pain and that it may
      act by inhibiting osteoclastic activity.

PMID- 22960544
TI  - The cholesterol content of the erythrocyte membrane is an important determinant
      of phosphatidylserine exposure.
AB  - Maintenance of the asymmetric distribution of phospholipids across the plasma
      membrane is a prerequisite for the survival of erythrocytes. Various stimuli have
      been shown to induce scrambling of phospholipids and thereby exposure of
      phosphatidylserine (PS). In two types of patients, both with aberrant plasma
      cholesterol levels, we observed an aberrant PS exposure in erythrocytes upon
      stimulation. We investigated the effect of high and low levels of cholesterol on
      the ATP-dependent flippase, which maintains phospholipid asymmetry, and the ATP
      independent scrambling activity, which breaks down phospholipid asymmetry. We
      analyzed erythrocytes of a patient with spur cell anemia, characterized by
      elevated plasma cholesterol, and the erythrocytes of Tangier disease patients
      with very low levels of plasma cholesterol. In normal erythrocytes, loaded with
      cholesterol or depleted of cholesterol in vitro, the same analyses were
      performed. Changes in the cholesterol/phospholipid ratio of erythrocytes had
      marked effects on PS exposure upon cell activation. Excess cholesterol profoundly
      inhibited PS exposure, whereas cholesterol depletion led to increased PS
      exposure. The activity of the ATP-dependent flippase was not changed, suggesting
      a major influence of cholesterol on the outward translocation of PS. The effects
      of cholesterol were not accompanied by eminent changes in cytoskeletal and
      membrane proteins. These findings emphasize the importance of cholesterol
      exchange between circulating plasma and the erythrocyte membrane as determinant
      for phosphatidylserine exposure in erythrocytes.

PMID- 22960545
TI  - Behaviour and hippocampus-specific changes in spiny mouse neonates after
      treatment of the mother with the viral-mimetic Poly I:C at mid-pregnancy.
AB  - Epidemiological studies have suggested a link between prenatal exposure to
      bacterial or viral infections and subsequent development of mental disorders such
      as schizophrenia and autism. Animal models to study the prenatal origin of such
      outcomes of pregnancy have largely used conventional rodents which are immature
      at birth compared to the human neonate, and doses of the infective agent (i.e.,
      lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour
      in the mother. In this study we have used the spiny mouse (Acomys cahirinus)
      whose offspring have completed organogenesis at birth, and a single subcutaneous
      injection of a low (0.5mg/kg) dose of polyriboinosinic-polyribocytidilic acid
      (Poly I:C) at mid gestation (20 days, term is 39 days). The treatment had no
      effect on maternal, fetal or neonatal survival, or postnatal growth of the
      offspring. However, offspring showed significant impairments in non-spatial
      memory and learning tasks, and motor activity. Brain histology examined at 1 and
      100 days of age revealed significant decreases in reelin, increased GFAP
      expression, and increased numbers of activated microglia, specifically in the
      hippocampus. This study provides evidence that a prenatal subclinical infection
      can have profound effects on brain development that are long-lasting.

PMID- 22960546
TI  - Microcystic macular degeneration from optic neuropathy.

PMID- 22960548
TI  - Involvement of arginine-vasopressin in the diuretic and hypotensive effects of
      Pereskia grandifolia Haw. (Cactaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pereskia grandifolia Haw. (Cactaceae), popularly
      known as "ora-pro-nobis" is well recognized in Brazilian traditional medicine as
      a diuretic agent, although no scientific data have been published to support this
      effect. The aim of this work is to evaluate the diuretic and hypotensive
      activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia
      grandifolia and possible mechanism of action. MATERIALS AND METHODS: The
      infusions (2.5-10%) and the HEPG (3-100 mg/kg) were orally administered in a
      single dose or daily (for seven days) to rats. The urine excretion rate, pH,
      density, conductivity and content of Na(+), K(+), Cl(-) and HCO(3)(-) were
      measured in the urine of saline-loaded animals. In collected serum samples the
      concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and
      angiotensin converting enzyme (ACE) activity were evaluated. The involvement of
      V(2) vasopressin receptor in the diuretic activity and the hypotensive effect of
      HEPG were also determined. RESULTS: Water excretion rate was significantly
      increased by HEPG, while the urinary K(+) and Cl(-) excretion was significantly
      reduced in acute and prolonged treatment. The oral administration of the HEPG
      (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial
      pressure (MAP) in normotensive rats. All other evaluated parameters have not been
      affected by any treatment. CONCLUSION: The results showed that HEPG could present
      compound(s) responsible for aquaretic activities with no signs of toxicity, and
      this effect could involve a reduction in the arginine-vasopressin release.

PMID- 22960547
TI  - Amniotic fluid stem cells to study mTOR signaling in differentiation.
AB  - The protein kinase mTOR is the central player within a pathway, which is known to
      be involved in the regulation of e.g., cell size, cell cycle, apoptosis,
      autophagy, aging and differentiation. mTOR activity responds to many signals,
      including cellular stress, oxygen, nutrient availability, energy status and
      growth factors. Deregulation of this enzyme is causatively involved in the
      molecular development of monogenic human diseases, cancer, obesity, type 2
      diabetes or neurodegeneration. Recently, mTOR has also been demonstrated to
      control stem cell homeostasis. A more detailed investigation of this new mTOR
      function will be of highest relevance to provide more explicit insights into stem
      cell regulation in the near future. Different cellular tools, including adult
      stem cells, embryonic stem cells or induced pluripotent stem cells could be used
      to investigate the role of mTOR in mammalian stem cell biology. Here we discuss
      the potential of amniotic fluid stem cells to become a promising cellular model
      to study the role of signaling cascades in stem cell homeostasis.

PMID- 22960549
TI  - Venom's antinociceptive property in the primitive ant Dinoponera quadriceps.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In northeastern Brazil, Dinoponera (Ponerinae)
      ants macerate are used to treat ear ache and its sting, rheumatism, and back
      pain. Such a popular use is a relevant fact that called for experimental
      evaluation of the antinociceptive activity of Dinoponera venom. MATERIALS AND
      METHODS: Dinoponera quadriceps venom (DqV; 5-500 MUg/kg; i.v.) or morphine (3.4
      mg/kg; s.c.) were evaluated in mice models of nociception (n=8 animals/group).
      Negative controls received sterile saline (0.9% NaCl; i.v.). RESULTS: DqV showed
      64% protein content and exhibited antinociceptive activity, without affecting
      motor function, in the tests: formalin (72%), writhing (52%), von Frey (71%) and
      hot plate (45%). The antinociceptive activity was abolished under protein
      denaturant conditions. CONCLUSIONS: This study provided the first demonstration
      of the antinociceptive property of Dinoponera quadriceps venom in mice models of
      chemical, mechanical and thermal nociception, corroborating the popular use and
      suggesting its potential therapeutic utilization in painful conditions.

PMID- 22960550
TI  - Effect of an aqueous extract of Cucurbita ficifolia Bouche on the glutathione
      redox cycle in mice with STZ-induced diabetes.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Cucurbita ficifolia is used in Mexican
      traditional medicine as an anti-diabetic and anti-inflammatory agent and its
      actions can be mediated by antioxidant mechanisms. Disturbance in the homeostasis
      of glutathione has been implicated in the etiology and progression of diabetes
      mellitus and its complications. MATERIAL AND METHODS: It was evaluated, the
      effect of an aqueous extract of Cucurbita ficifolia on glycemia, plasma lipid
      peroxidation; as well as levels of reduced (GSH) and oxidized (GSSG) glutathione
      and activities of enzymes involved in glutathione redox cycle: glutathione
      peroxidase (GPx) and glutathione reductase (GR) in liver, pancreas, kidney and
      heart homogenates of streptozotocin-induced diabetic mice. RESULTS: Increased
      blood glucose and lipid peroxidation, together with decreased of GSH
      concentration, GSH/GSSG ratio and its redox potential (E(h)), and enhanced
      activity of GPx and GR in liver, pancreas and kidney were the salient features
      observed in diabetic mice. Administration of the aqueous extract of Cucurbita
      ficifolia to diabetic mice for 30 days, used at a dose of 200 mg/kg, resulted in
      a significant reduction in glycemia, polydipsia, hyperphagia and plasma lipid
      peroxidation. Moreover, GSH was increased in liver, pancreas and kidney, and GSSG
      was reduced in liver, pancreas and heart, therefore GSH/GSSG ratio and its E(h)
      were restored. Also, the activities involved in the glutathione cycle were
      decreased, reaching similar values to controls. CONCLUSIONS: An aqueous extract
      of Cucurbita ficifolia with hypoglycemic action, improve GSH redox state,
      increasing glutathione pool, GSH, GSH/GSSG ratio and its E(h), mechanism that can
      explain, at least in part, its antioxidant properties, supporting its use as an
      alternative treatment for the control of diabetes mellitus, and prevent the
      induction of complications by oxidative stress.

PMID- 22960551
TI  - An antimicrobial evaluation of plants used for the treatment of respiratory
      infections in rural Maputaland, KwaZulu-Natal, South Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Abundant availability of medicinal plants in the
      study area offers low cost health care, but scientific validation is needed in
      order to lend credibility to the traditional use against respiratory infections.
      AIM OF THE STUDY: This study focussed on determining the antimicrobial efficacies
      of 30 plant species (independently and in various combinations) used for
      respiratory related infections in rural Maputaland. MATERIALS AND METHODS: In
      vitro minimum inhibitory concentration (MIC) assays were undertaken on
      dichloromethane-methanol (CH(2)Cl(2): MeOH) and aqueous extracts, as well as the
      hydro-distilled essential oils (for aromatic plants). Selected plant parts were
      assessed for antimicrobial activity against a range of respiratory pathogens i.e.
      Cryptococcus neoformans (ATCC 14116), Klebsiella pneumoniae (ATCC 13883),
      Moraxella catarrhalis (ATCC 23246), Mycobacterium smegmatis (ATCC 14468) and
      Staphylococcus aureus (ATCC 6538). The sum of the fractional inhibitory
      concentrations (?FIC) was determined for plants traditionally used in
      combination. Isobolograms represent MIC values for a selection of interactions
      where two plants were combined in various ratios. RESULTS: The most
      antimicrobially active aqueous extracts were that of Ozoroa obovata and
      Sclerocarya birrea (0.10 mg/ml) while organic extracts from Parinari capensis
      subsp. incohata and Tetradenia riparia demonstrated the most noteworthy (0.03
      mg/ml) activity. Although both Lippia javanica and Eucalyptus grandis were by far
      the most popular plants traditionally used for respiratory infections, the
      antimicrobial activity was mostly only moderate. Furthermore, the traditional use
      in a 1:1 combination did not display strong antimicrobial interactions, but
      isobolograms demonstrate (against some test organisms) that when combined in
      various ratios, predominant additive interactions are evident where E. grandis
      was present in larger proportions. The combination of E. grandis with O. obovata
      demonstrated synergism against both C. neoformans and K. pneumoniae, with ?FIC
      values of 0.34 and 0.28 respectively. Various ratios of these two plants also
      demonstrated a predominantly synergistic profile. CONCLUSION: Although this in
      vitro study supports the traditional use of some plants independently and in
      combination for the treatment of respiratory ailments in rural Maputaland,
      results demonstrate that the traditional selection of plants in higher frequency
      do not necessarily correlate with higher antimicrobial efficacy.

PMID- 22960552
TI  - Maricaulis maris cation diffusion facilitator: achieving homogeneity through a
      mixed-micelle approach.
AB  - One of the most common problems encountered during isolation and purification of
      homogenous membrane proteins is their aggregation which in turn makes the
      obtained material unsuitable for structural and functional studies. As various
      detergents can have a different impact on the protein stability and solubility,
      introducing the protein to different detergent micelles can result in the removal
      of such aggregation. Here we describe a method for retrieving homogenous samples
      of a putative member of the cation diffusion facilitator family from the marine
      bacterium Maricaulis maris (MmCDF3). A feature that makes this 23kDa protein
      particularly interesting to study is that it lacks the cytoplasmic domain that in
      other members of the CDF family protrudes into the cytoplasm and that was
      proposed to play a crucial role in the metal transport. The MmCDF3 was produced
      with the C-terminal hexahistidine tag in Escherichia coli and subsequently
      purified using affinity chromatography followed by gel-filtration yielding 7.5mg
      of the pure transporter. However, solubilization and purification of the protein
      in a single detergent or a complete detergent exchange to another single
      detergent invariably resulted in the formation of protein aggregates. Instead, if
      the protein was introduced into a micelle of multiple detergents, the aggregation
      level notably decreased. Purification of the protein in a mixture of n-dodecyl
      beta-D-maltoside and Fos-choline-12 at a ratio of 4 to 1 allowed for recovery of
      3.7mg of homogenous, non-aggregated MmCDF3 from 1L of bacterial culture that
      could easily be separated from aggregated material.

PMID- 22960553
TI  - Specific and non-overlapping functions of testosterone and 11-ketotestosterone in
      the regulation of professional phagocyte responses in the teleost fish gilthead
      seabream.
AB  - Sex hormones, both estrogens and androgens, have a strong impact on immunity in
      mammals. In fish, the role of androgens in immunity has received little attention
      and contradictory conclusions have been obtained. However, it is well known that
      sex steroids are involved in fish growth, osmoregulation and gonad remodelation.
      In this study, we examine the in vitro effects of testosterone and 11
      ketotestosterone, the two main fish androgens, on the professional phagocytes of
      the teleost fish gilthead seabream (Sparus aurata L.). Although both testosterone
      and 11-ketotestosterone failed to modulate the respiratory burst of seabream
      phagocytes, testosterone but not 11-ketotestosterone was able to increase the
      phagocytic ability of non-activated phagocytes. Curiously, 11-ketotestosterone
      was more powerful than testosterone at inducing the expression of its own
      receptor, namely androgen receptor b (ARb), in acidophilic granulocytes (AGs),
      but none of them affected the basal ARb expression levels in macrophages (MO).
      Furthermore, although physiological concentrations of testosterone exerted a pro
      inflammatory effect on both AGs and MOs, 11-ketotestosterone showed an anti
      inflammatory effect in AGs and a strong pro-inflammatory effect in MOs.
      Interestingly, both androgens modulated the expression of toll-like receptors in
      these two immune cell types, suggesting that androgens might regulate the
      sensitivity of phagocytes to pathogens and damage signals. Testosterone and 11
      ketotestosterone have a competitive effect, at least, on the modulation of the
      expression of some genes. Therefore, our results show for the first time a non
      overlapping role for testosterone and 11-ketotestosterone in the regulation of
      professional phagocyte functions in fish.

PMID- 22960554
TI  - Novel insights in localization and expression levels of C5aR and C5L2 under
      native and post-transplant conditions in the kidney.
AB  - AIMS: The complement system, and especially C5a, plays an important role in the
      pathophysiology of renal diseases and post-transplant renal injury. The two
      receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only
      renal C5aR expression has been reported, although exact localization and
      alterations in expression after transplantation are unknown. MATERIALS AND
      RESULTS: Renal C5aR and C5L2 expression and localization were analyzed
      immunohistochemically. C5aR and C5L2 expression was analyzed in human kidney
      biopsies obtained from living donors and patients suffering from acute tubular
      necrosis, acute cellular and vascular rejection or IF/TA. C5aR was expressed in
      the thick ascending limb of Henle's loop and first part of the distal convoluted
      tubule (DCT). Under inflammatory conditions, C5aR was de novo expressed in
      proximal tubuli. C5L2 was expressed in the kidney and localized to DCT1, DCT2 and
      connecting tubule. Persistent distal tubular expression of both receptors was
      demonstrated after renal transplantation. CONCLUSIONS: This study shows distinct
      renal expression patterns for C5aR and C5L2. Our findings suggest a functional
      role for renal C5L2 rather than being a C5a decoy receptor. Future studies
      focusing on renal C5a-C5aR interaction should take differential C5aR and C5L2
      expression into account, alongside abundant C5aR expression on infiltrating
      cells.

PMID- 22960555
TI  - Targeting the microenvironment in chronic lymphocytic leukemia is changing the
      therapeutic landscape.
AB  - PURPOSE OF REVIEW: Despite ongoing efforts to decipher the cancer genome,
      discoveries of new targetable genetic lesions within cancer cells are rare.
      Therefore, alternative approaches are needed. Signals from the microenvironment
      are increasingly recognized as drivers of disease progression in hematologic and
      solid cancers. Consequently, there is growing interest in targeting the tumor
      microenvironment cross-talk. This review highlights recent therapeutic advances
      in targeting the microenvironment in chronic lymphocytic leukemia (CLL). RECENT
      FINDINGS: CLL is the poster child for microenvironment-dependent malignancies,
      because the clonal CLL B cells are highly dependent on external signals for
      maintenance and expansion. These pathways recapitulate those responsible for
      normal B-cell expansion in germinal centers. The most prominent, conserved
      mechanism is B-cell receptor (BCR) signaling, which promotes CLL cell survival
      and expansion in lymphatic tissue areas designated proliferation centers. BCR
      signaling now can be targeted by new targeted kinase inhibitors. SUMMARY: Small
      molecule inhibitors of BCR signaling kinases, Bruton's tyrosine kinase (Btk)
      inhibitor ibrutinib and the phosphoinositide 3'-kinase delta (PI3Kdelta)
      inhibitor GS-1101, are currently transforming the landscape of CLL therapy. This
      development exemplifies that the microenvironment has become a lively successful
      area of translational research.

PMID- 22960556
TI  - Phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway
      inhibition:  a breakthrough in the management of luminal (ER+/HER2-) breast
      cancers?
AB  - PURPOSE OF REVIEW: Recent data from clinical trials evaluating mammalian target
      of rapamycin (mTOR) inhibitors in the setting of endocrine resistance in luminal
      (estrogen receptor-positive, human epidermal growth factor receptor 2-negative)
      breast cancers have validated this pathway as a bona-fide therapeutic target in
      this setting. There are currently many agents under clinical investigation that
      inhibit the phosphatidylinositol 3-kinase (PI3K) pathway. We review these
      findings in the context of the preclinical data and the current status of
      biomarker development in this field. RECENT FINDINGS: Clinical trials in the
      neoadjuvant (RAD2222) and metastatic setting (TAMRAD, BOLERO-2) have reported
      improved clinical outcome of patients with unselected luminal breast cancer
      through the addition of mTOR inhibitors to standard endocrine treatment. PI3K
      molecular aberrations are frequently found in luminal breast cancer, yet the role
      of these in defining patients' prognosis and response to PI3K/AKT/mTOR inhibitors
      remains to be determined. SUMMARY: Therapeutic targeting of the PI3K pathway
      promises improved clinical outcome for patients with luminal breast cancer.
      Correspondingly, agents that target this pathway are entering the clinic at an
      unprecedented rate. Future clinical trials that incorporate correlative
      translational research will help us decipher important information critical for
      successful development of these agents in breast cancer: which part of the
      pathway should be targeted and in which clinical scenario; and which patients are
      more likely to benefit from these drugs, particularly in the adjuvant setting.

PMID- 22960557
TI  - Advances in the management of follicular lymphoma.
AB  - PURPOSE OF REVIEW: Antibody-based therapy has revolutionized treatment strategies
      in follicular lymphoma. This review focuses on current standards and recent
      innovations in the management of the disease. RECENT FINDINGS: Understanding the
      mechanism of action of antibodies led to the development of next generation CD20
      antibodies, antibodies targeting other molecules and bispecific antibodies. With
      obinutuzumab, a promising next generation of CD20 antibodies has entered phase
      III of clinical trials. The bispecific T-cell engager blinatumomab combines
      targeted therapy with immunologic activation of T cells exerting cytotoxic
      activity on the target cells. Apart from antibodies, small molecules targeting
      key pathways in lymphoma have shown promising activity in vitro and are currently
      in clinical development. SUMMARY: A wealth of new substances has entered various
      stages of clinical trials and has yet to show superiority over rituximab-based
      immunochemotherapy. Intelligent therapeutic regimens containing these drugs have
      to be developed. Large randomized trials comparing promising treatment options
      are urgently needed.

PMID- 22960558
TI  - Allogeneic hematopoietic stem cell transplantation for multiple myeloma: 
      curative but not the standard of care.
AB  - PURPOSE OF REVIEW: Despite the curative potential of allogeneic hematopoietic
      stem cell transplantation (allo HSCT) for patients with multiple myeloma, and
      reduction of transplant-related mortality with nonmyeloablative transplant
      approaches, rates of acute and chronic graft-versus-host disease and disease
      progression remain high. It is unclear if nonmyeloablative transplants are more
      effective than autologous (auto). Novel promising drugs and maintenance treatment
      strategies following auto SCT may also delay allo transplantation. In this
      review, we summarize the emerging data on allo HSCT and provide suggestions for
      its optimal role in the treatment of myeloma. RECENT FINDINGS: Large cooperative
      group studies comparing allo HSCT with auto SCT as frontline therapy have been
      performed with reduced intensity conditioning regimens using unmanipulated
      peripheral blood stem cells from human leukocyte antigen (HLA)-compatible donors
      and standard calcineurin inhibitor graft-versus-host disease prophylaxis. Two
      recent reports show conflicting data. Although the Blood and Marrow Transplant
      Clinical Trials Network 0102 study demonstrated no progression-free or overall
      survival advantage at 3 years, a European study demonstrated superior 5-year
      outcome after auto/HLA-matched sibling allo HSCT compared with tandem auto SCT in
      previously untreated multiple myeloma patients. The advent of maintenance therapy
      could potentially improve outcomes of both transplant types. SUMMARY: High rates
      of acute and chronic graft-versus-host disease currently limit the implementation
      of nonmyeloablative allo HSCT. Novel approaches are required so that patients
      with myeloma can undergo allo HSCT before resistance develops to standard drug
      combinations.

PMID- 22960559
TI  - New standards of care in the management of the axilla.
AB  - PURPOSE OF REVIEW: The management of the axilla in early breast cancer remains
      controversial. This review describes the current literature focussing on the
      management of the clinically negative axilla. RECENT FINDINGS: For women with
      isolated tumour cells or micrometastases [nodal deposit(s) >0.2-2  mm] in one or
      more axillary nodes, disease-free survival may be reduced, without a significant
      impact on overall survival. For macrometastases (node deposits >2  mm), the
      convention of axillary clearance has been challenged. Axillary clearance compared
      with no surgery in patients undergoing breast conservation in women with
      predominantly small, estrogen receptor-positive, low-grade cancers receiving
      systemic therapy demonstrated no difference in disease-free survival or overall
      survival. However, the confounding treatment by axillary radiotherapy (alongside
      breast radiotherapy) is in keeping with improved disease-free survival in
      conservation patients treated with breast and axillary radiotherapy compared with
      those treated with breast radiotherapy alone. Direct prospective comparison of
      axillary clearance and radiotherapy is eagerly awaited. SUMMARY: Further
      information is still required to define which patients with low-volume
      macrometastatic axillary disease may not require further local treatment and
      whether surgery or radiotherapy is equally effective in treating the node
      positive axilla.

PMID- 22960560
TI  - TA strategy for rapid and efficient site-directed mutagenesis.
AB  - A simple, rapid, and efficient site-directed mutagenesis method using TA strategy
      with synthetic mutagenic oligonucleotides is described. Briefly, a 3' A-overhang
      vector was prepared by polymerase chain reaction (PCR) using a classical Taq
      polymerase with terminal transferase activity, a reverse vector primer starting
      the complement nucleotide prior to the 5' end adenosine of the target, and a
      forward vector primer starting the nucleotide posterior to the 3' end thymidine.
      The 3' T-overhang mutagenic double-strand oligonucleotide was synthesized and
      cloned directly into the PCR-amplified 3' A-overhang vector. Thus, direct
      ligation of synthetic mutagenic oligonucleotides and PCR-amplified vector via TA
      sticky ends provides us with simple, rapid, and efficient site-directed
      mutagenesis.

PMID- 22960561
TI  - Simultaneous detection of three CNS indicator proteins in complex suspensions
      using a single immuno-PCR protocol.
AB  - The diagnosis of infections and protection against their transmission are aided
      greatly by determination of indicator proteins. However, protein assays are
      mostly restricted to single-antigen determinations and are often limited in
      sensitivity and specificity. Consequently, there is a large demand for high
      sensitivity immunoassays for analysis of several antigens in protein suspensions.
      A novel immuno-polymerase chain reaction (PCR) assay is described for the
      simultaneous detection of central nervous system (CNS) indicators such as the
      neuron-specific enolase, the glial fibrillary acid protein, and the cellular
      prion protein. Coated antigens are immunocomplexed with specific antibodies and a
      DNA fragment is subsequently amplified by PCR. The PCR product obtained
      corresponds to the antigen signal. Background signals are a critical factor,
      primarily when using complex protein suspensions, but we were able to reduce
      background noise dramatically by including two heating steps, the first for
      protein denaturation and the second for detachment of immunocomplexed DNA,
      enabling optimal DNA amplification. Using these methods and depending on the
      antigen and antibody affinity, a sensitivity enhancement of 2 to 3 orders of
      magnitude is achieved for CNS indicator detection using the immuno-PCR approach
      compared with ELISA procedures carried out under identical conditions.

PMID- 22960562
TI  - Practice on dummies: the safe way to learn.

PMID- 22960563
TI  - STIs: options & considerations.

PMID- 22960564
TI  - Rapid and sensitive detection of shrimp yellow head virus using loop-mediated
      isothermal amplification and a colorogenic nanogold hybridization probe.
AB  - Salt-induced self-aggregation of gold nanoparticles (AuNP) carrying unisense
      ssDNA probes can be prevented specifically by complementary DNA. Loop-mediated
      isothermal amplification (LAMP) can amplify DNA rapidly. Here, the two techniques
      were combined to detect yellow head virus (YHV). The LAMP-AuNP method required 60
      min for LAMP and 5 min for hybridization of LAMP products to an AuNP-labeled
      ssDNA probe followed by salt induced probe-particle aggregation to visualize
      color development. The detection sensitivity of the method was comparable to that
      of the commercial IQ2000TM nested RT-PCR but only required ~65 min to produce a
      result, and did not cross-detect other shrimp viruses. As the LAMP-AuNP protocol
      only requires a heating block, it offers opportunities for rapid detection of
      YHV.

PMID- 22960565
TI  - Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice
      treated with metformin.
AB  - Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin
      resistance. Metformin, a widely known anti-diabetic drug, used for patients with
      type 2 diabetes mellitus, is also claimed to be useful in treatment of NAFLD.
      However, both the clinical efficacy and the putative mechanisms underlying the
      clinical effects of metformin in treating NAFLD are unclear. Adenosine
      monophosphate-activated protein kinase (AMPK), the primary molecular target for
      metformin, is a known regulator of mitochondrial function. Thus, we used a
      proteomic approach to investigate the effect of metformin on liver mitochondria
      of apolipoprotein E knockout (apoE(-/-)) mice, an animal model of NAFLD. Two
      dimensional electrophoresis coupled with mass spectrometry was applied to study
      the changes in liver mitochondrial protein expression in 6-month old metformin
      treated apoE(-/-) mice as compared to non-treated animals. Collectively, 25
      differentially expressed proteins were indentified upon metformin treatment
      including proteins related to metabolism, oxidative stress and cellular
      respiration. The most up-regulated protein was glycine N-methyltransferase (GNMT)
      - an enzyme, whose deficiency was shown to be directly related to the development
      of NAFLD. Our results clearly point to the strong mitochondrial action of
      metformin in NAFLD. Up-regulation of GNMT may represent an important mechanism of
      beneficial action of metformin in NAFLD treatment.

PMID- 22960566
TI  - Differential regulation of OmpC and OmpF by AtpB in Escherichia coli exposed to
      nalidixic acid and chlortetracycline.
AB  - Little is known about mechanisms through which OmpR/EnvZ and CpxA/CpxR regulate
      the expression of OmpC and OmpF, and thereby regulate bacterial responses to
      antibiotics exposure. In this study we investigated the relationships among OmpC,
      OmpF and TCSs using Escherichia coli strains with the deletion of ompR, envZ,
      cpxA and cpxR genes and antibiotics nalidixic acid and chlortetracycline.
      Significant changes at expression levels of OmpC and OmpF were detected in the
      strains exposed to the antibiotics. Outer membrane proteins that were altered in
      response to the changes of OmpC and OmpF expression levels were identified using
      proteomics approaches and the networks involved in the regulation of protein
      changes in response to the antibiotic exposure were constructed. It was found
      that AtpB was upregulated and downregulated in parallel with the reduced and
      elevated expression of OmpC in response to chlortetracycline and nalidixic acid
      exposure, respectively and the change of AtpB was regulated by CpxR. These
      findings were validated by the detection of OmpC, OmpF and CpxR changes in
      DeltaatpD and DeltaphoE. Therefore, this study provides novel insight into the
      regulation network of TCSs and OM proteins involved in the differential responses
      of bacteria to different classes of antibiotics.

PMID- 22960567
TI  - Acute coronary angiography in patients resuscitated from out-of-hospital cardiac
      arrest--a systematic review and meta-analysis.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest has a poor prognosis. The main
      aetiology is ischaemic heart disease. AIM: To make a systematic review addressing
      the question: "In patients with return of spontaneous circulation following out
      of-hospital cardiac arrest, does acute coronary angiography with coronary
      intervention improve survival compared to conventional treatment?" METHODS: Peer
      reviewed articles written in English with relevant prognostic data were included.
      Comparison studies on patients with and without acute coronary angiography were
      pooled in a meta-analysis. RESULTS: Thirty-two non-randomised studies were
      included of which 22 were case-series without patients with conservative
      treatment. Seven studies with specific efforts to control confounding had
      statistical evidence to support the use of acute coronary angiography following
      resuscitation from out-of-hospital cardiac arrest. The remaining 25 studies were
      considered neutral. Following acute coronary angiography, the survival to
      hospital discharge, 30 days or six months ranged from 23% to 86%. In patients
      without an obvious non-cardiac aetiology, the prevalence of significant coronary
      artery disease ranged from 59% to 71%. Electrocardiographic findings were
      unreliable for identifying angiographic findings of acute coronary syndrome. Ten
      comparison studies demonstrated a pooled unadjusted odds ratio for survival of
      2.78 (1.89; 4.10) favouring acute coronary angiography. CONCLUSION: No randomised
      studies exist on acute coronary angiography following out-of-hospital cardiac
      arrest. An increasing number of observational studies support feasibility and a
      possible survival benefit of an early invasive approach. In patients without an
      obvious non-cardiac aetiology, acute coronary angiography should be strongly
      considered irrespective of electrocardiographic findings due to a high prevalence
      of coronary artery disease.

PMID- 22960568
TI  - Death to discharge--devil in the details--or not?

PMID- 22960569
TI  - Evaluation of non-linear equations to model different animal growths with mono
      and bisigmoid profiles.
AB  - Experimental data of different animals (e.g. cocks, pigs, cats, dogs, cattles,
      etc.) from recent bibliography were selected to evaluate the capability of five
      classical sigmoidal equations (i.e. Bertalanffy, Weibull, logistic, Gompertz, and
      modified Hill) to model growth. These functions were used in different
      reparameterized forms in order to define all growth phases and to characterize
      significant kinetic parameters. The results indicated that logistic and Weibull
      equations were the best options to simulate the data with mono-sigmoid profiles.
      A subsequent formulation of logistic and Gompertz equations was constructed to
      describe accurately the biphasic trends for cock and foal growths.

PMID- 22960570
TI  - Perceptual advertisement by the prey of stalking or ambushing predators.
AB  - There has been previous theoretical explorations of the stability of signals by
      prey that they have detected a stalking or ambush predator, where such perceptual
      advertisement dissuades the predator from attacking. Here we use a game
      theoretical model to extend the theory to consider some empirically-motivated
      complexities: (i) many perceptual advertisement signals appear to have the
      potential to vary in intensity, (ii) higher intensity signals are likely to be
      most costly to produce, and (iii) some high-cost signals (such as staring
      directly at the predator) can only be utilised if the prey is very confident of
      the existence of a nearby predator (that is, there are reserved or unfakable
      signals). We demonstrate that these complexities still allow for stable
      signalling. However, we do not find solutions where prey use a range of signal
      intensities to signal different degrees of confidence in the proximity of a
      predator; with prey simply adopting a binary response of not signalling or always
      signalling at the same fixed level. However this fixed level will not always be
      the cheapest possible signal, and we predict that prey that require more
      certainty about proximity of a predator will use higher-cost signals. The
      availability of reserved signals does not prohibit the stability of signalling
      based on lower-cost signals, but we also find circumstances where only the
      reserved signal is used. We discuss the potential to empirically test our model
      predictions, and to develop theory further to allow perceptual advertisement to
      be combined with other signalling functions.

PMID- 22960571
TI  - Effects of codon sequence on the dynamics of genetic networks.
AB  - In prokaryotes, the rate at which codons are translated varies from one codon to
      the next. Using a stochastic model of transcription and translation at the
      nucleotide and codon levels, we investigate the effects of the codon sequence on
      the dynamics of protein numbers. For sequences generated according to the codon
      frequencies in Escherichia coli, we find that mean protein numbers at near
      equilibrium differ with the codon sequence, due to the mean codon translation
      efficiencies, in particular of the codons at the ribosome binding site region. We
      find close agreement between these predictions and measurements of protein
      expression levels as a function of the codon sequence. Next, we investigate the
      effects of short codon sequences at the start/end of the RNA sequence with
      linearly increasing/decreasing translation efficiencies, known as slow ramps. The
      ramps affect the mean, but not the fluctuations, in proteins numbers by affecting
      the rate of translation initiation. Finally, we show that slow ramps affect the
      dynamics of small genetic circuits, namely, switches and clocks. In switches,
      ramps affect the frequency of switching and bias the robustness of the noisy
      attractors. In repressilators, ramps alter the robustness of periodicity. We
      conclude that codon sequences affect the dynamics of gene expression and genetic
      circuits and, thus, are likely to be under selection regarding both mean codon
      frequency as well as spatial arrangement along the sequence.

PMID- 22960572
TI  - The effects of movement pattern modification on lower extremity kinematics and
      pain in women with patellofemoral pain.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To compare hip and knee
      kinematics and pain during a single-limb squat between 3 movement conditions
      (usual, exaggerated dynamic knee valgus, corrected dynamic knee valgus) in women
      with patellofemoral pain. BACKGROUND: Altered kinematics (increased hip
      adduction, hip medial rotation, knee abduction, and knee lateral rotation,
      collectively termed dynamic knee valgus) have been proposed to contribute to
      patellofemoral pain; however, cross-sectional study designs prevent interpreting
      a causal link between kinematics and pain. METHODS: The study sample included 20
      women with patellofemoral pain, who demonstrated observable dynamic knee valgus.
      Participants performed single-limb squats under usual, exaggerated, and corrected
      movement conditions. Pain during each condition was assessed using a 0-to-100-mm
      visual analog scale. Hip and knee frontal and transverse plane angles at peak
      knee flexion and pain levels were compared using repeated-measures 1-way analyses
      of variance. Pearson correlation coefficients were used to determine within
      condition associations between kinematic variables and pain. RESULTS: In the
      exaggerated compared to the usual condition, increases were detected in hip
      medial rotation (mean +/- SD difference, 5.8 degrees  +/- 3.2 degrees ; P<.001),
      knee lateral rotation (5.5 degrees  +/- 4.9 degrees , P<.001), and pain (8.5 +/-
      10.8 mm, P = .007). In the corrected compared to the usual condition, decreases
      were detected in hip adduction (mean +/- SD difference, 3.5 degrees  +/- 3.7
      degrees ; P = .001) and knee lateral rotation (1.6 degrees  +/- 2.8 degrees , P =
      .06); however, average pain was not decreased (1.2 +/- 14.8 mm, P = 1.0). Pain
      was correlated with knee lateral rotation in the usual (r = -0.47, P = .04) and
      exaggerated (r = -0.49, P = .03) conditions. In the corrected condition, pain was
      correlated with hip medial rotation (r = 0.44, P = .05) and knee adduction (r =
      0.52, P = .02). CONCLUSION: Avoiding dynamic knee valgus may be an important
      component of rehabilitation programs in women with patellofemoral pain, as this
      movement pattern is associated with increased pain.

PMID- 22960574
TI  - Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell
      growth by autophagy and apoptosis in vitro and in vivo.
AB  - TMEM166 is a novel programmed cell death-related molecule. In this report, we
      constructed a recombinant adenovirus 5-TMEM166 vector (Ad5-TMEM166) and evaluated
      its expression and anti-tumor activities in vitro and in vivo. Cell viability
      analysis revealed that the adenovirus-mediated increase of TMEM166 inhibited
      tumor cell growth in a dose- and time-dependent manner. This inhibitory effect
      was mediated by both autophagy (via inhibition of mTOR and activation of p70S6K)
      and apoptosis (via caspase-3 activation), both of which contributed to cell death
      and suppression of tumorigenicity. Our data indicated that Ad5-TMEM166 may be a
      novel gene therapy candidate for cancer.

PMID- 22960573
TI  - The analysis of DNA adducts: the transition from (32)P-postlabeling to mass
      spectrometry.
AB  - The technique of (32)P-postlabeling, which was introduced in 1982 for the
      analysis of DNA adducts, has long been the method of choice for in vivo studies
      because of its high sensitivity as it requires only <10MUg DNA to achieve the
      detection of 1 adduct in 10(10) normal bases. (32)P-postlabeling has therefore
      been utilized in numerous human and animal studies of DNA adduct formation. Like
      all techniques (32)P-postlabeling does have several disadvantages including the
      use of radioactive phosphorus, lack of internal standards, and perhaps most
      significantly does not provide any structural information for positive
      identification of unknown adducts, a shortcoming that could significantly hamper
      progress in the field. Structural methods have since been developed to allow for
      positive identification of DNA adducts, but to this day, the same level of
      sensitivity and low sample requirements provided by (32)P-postlabeling have not
      been matched. In this mini review we will discuss the (32)P-postlabeling method
      and chronicle the transition to mass spectrometry via the hyphenation of gas
      chromatography, capillary electrophoresis, and ultimately liquid chromatography
      which, some 30years later, is only just starting to approach the sensitivity and
      low sample requirements of (32)P-postlabeling. This paper focuses on the
      detection of bulky carcinogen-DNA adducts, with no mention of oxidative damage or
      small alkylating agents. This is because the (32)P-postlabeling assay is most
      compatible with bulky DNA adducts. This will also allow a more comprehensive
      focus on a subject that has been our particular interest since 1990. 

PMID- 22960575
TI  - Tackling autoimmunity with gene therapy.
AB  - Autoimmune diseases result from an aberrant response of the immune system that
      target self-tissues. Our understanding of normal immune development has been used
      to subvert this self-reactivity and involves exposing self-antigen to the
      developing immune system. This can be achieved through bone marrow derived cells,
      thus introducing potential clinical application. We have used the mouse model of
      multiple sclerosis to demonstrate that the transfer of bone marrow encoding a
      target autoantigen can be used to promote immune tolerance. The process of
      preconditioning recipients for hematopoietic stem cell transfer is critical for
      potential human translation. Thus, we have directly addressed if our model can
      also be applied in non-myeloablative and less toxic conditioning to promote
      tolerance and reverse established disease. Our studies to date indicate that this
      can indeed be achieved and that only low levels of chimerism are required to
      achieve tolerance.

PMID- 22960576
TI  - Redox regulation of cancer cell migration and invasion.
AB  - Cancer cell migration and invasion are the initial steps in metastasis. Through a
      series of cellular events, including cytoskeletal remodeling resulting in
      phenotype changes and degradation of the extracellular matrix, cells are able to
      detach from the primary tumor and metastasize to distant sites. These changes
      occur in response to intracellular signaling mechanisms triggered via cell
      surface receptor stimulation or signal amplification within the cell. Amongst the
      active molecules that participate in relaying cellular signals are the reactive
      oxygen species (ROS). Initially identified to participate in defense mechanisms
      to ward off invading pathogens, ROS are now considered to have important roles in
      several other biological processes including cancer development. In this report,
      we review recent evidence pointing towards the involvement of ROS in tumor
      progression. We discuss the biology of ROS and their roles at different stages
      during the process of cancer cell migration and invasion.

PMID- 22960577
TI  - Modulations of gene expression induced by daily ultraviolet light can be
      prevented by a broad spectrum sunscreen.
AB  - Realistic non-zenithal solar ultraviolet (UV) exposure, obtained using standard
      ultraviolet daylight spectrum (DUVR), has deleterious impact on epidermal and
      dermal compartments of human skin. The present study was designed to assess gene
      expression in human reconstructed skin following exposure to DUVR and the
      protective effect of a broad spectrum sunscreen. Reconstructed skins were exposed
      to a realistic daily UV dose of 12 J/cm(2) DUVR in the presence of a sunscreen
      product (Sun(burn) Protection Factor (SPF)=13 and UVA protection factor UVAPF
      (PPD) 10.5) or its vehicle. Six hours post exposure, gene expression was
      investigated in fibroblasts (225 genes) and keratinocytes (244 genes) separately
      using quantitative PCR arrays. DUVR exposure led to significant modulation of 35
      and 66 genes in fibroblasts and keratinocytes, respectively. These genes were
      involved in extracellular matrix homeostasis, oxidative stress response, cell
      growth, inflammation and epidermal differentiation. Sunscreen use significantly
      reduced DUVR-induced gene modulation. Hierarchical clustering showed that gene
      expression profiles in protected and DUVR-exposed samples were very close to
      those of unexposed samples. The number of DUVR-modulated genes was significantly
      decreased by tested sunscreen (zero and four modulated genes in fibroblasts and
      keratinocytes, respectively). Our results demonstrate that a broad-spectrum
      sunscreen product is highly effective in protecting reconstructed human skin
      against DUVR-induced changes in gene expression.

PMID- 22960580
TI  - Cyclic AMP relaxation of rat aortic smooth muscle is mediated in part by decrease
      of depletion of intracellular Ca(2+) stores and inhibition of capacitative
      calcium entry.
AB  - Despite a large number of studies, the mechanism by which 3',5'-cyclic
      monophosphate (cAMP) induces vasorelaxation is not fully understood. The
      comparison between results obtained in different vessels or species has often
      been the source of conflicting reports. In order to shed more light onto this
      mechanism, we studied the effects of forskolin in phenylephrine-pre-contracted
      endothelium-denuded rat aorta and measured cAMP levels in rat aortic myocytes by
      enzyme-immunoassay. Nanomolar forskolin relaxed phenylephrine-induced
      contractions. This effect was mimicked by dibutyryl-cAMP and was potentiated by
      rolipram or a p38-mitogen-activated protein kinase (p38-MAPK) inhibitor (SB
      203580). Nifedipine and verapamil partially relaxed phenylephrine-induced
      contractions, while further application of cAMP-elevating agents fully relaxed
      these contractions. In Ca(2+)-free extracellular solution, forskolin reduced
      phenylephrine-induced transient contractions and reduced the Ca(2+)-induced
      contraction after depletion of intracellular stores. Nanomolar concentrations of
      forskolin increased basal cAMP levels only in the presence of rolipram or
      phenylephrine, which did not modify intracellular levels of cAMP by themselves.
      In conclusion, relaxation by cAMP is mediated in part by decrease of depletion of
      intracellular Ca(2+) stores and inhibition of capacitative calcium entry. This
      study provides the first evidence that inhibition of PDE4 or p38-MAPK potentiates
      the vasodilator effect of cAMP-elevating agents in rat aortic myocytes.

PMID- 22960578
TI  - Zinc and the modulation of redox homeostasis.
AB  - Zinc, a redox-inactive metal, has been long viewed as a component of the
      antioxidant network, and growing evidence points to its involvement in redox
      regulated signaling. These actions are exerted through several mechanisms based
      on the unique chemical and functional properties of zinc. Overall, zinc
      contributes to maintaining the cell redox balance through various mechanisms
      including: (i) the regulation of oxidant production and metal-induced oxidative
      damage; (ii) the dynamic association of zinc with sulfur in protein cysteine
      clusters, from which the metal can be released by nitric oxide, peroxides,
      oxidized glutathione, and other thiol oxidant species; (iii) zinc-mediated
      induction of the zinc-binding protein metallothionein, which releases the metal
      under oxidative conditions and acts per se as a scavenging oxidant; (iv) the
      involvement of zinc in the regulation of glutathione metabolism and of the
      overall protein thiol redox status; and (v) a direct or indirect regulation of
      redox signaling. Findings of oxidative stress, altered redox signaling, and
      associated cell/tissue dysfunction in cell and animal models of zinc deficiency
      highlight the relevant role of zinc in the preservation of cell redox
      homeostasis. However, although the participation of zinc in antioxidant
      protection, redox sensing, and redox-regulated signaling is accepted, the
      molecules, targets, and mechanisms involved are still partially known and the
      subject of active research.

PMID- 22960579
TI  - Outcome of infection of C57BL/6 IL-10(-/-) mice with Campylobacter jejuni strains
      is correlated with genome content of open reading frames up- and down-regulated
      in vivo.
AB  - Human Campylobacter jejuni infection can result in an asymptomatic carrier state,
      watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological
      sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with
      twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate
      colonization and disease phenotypes with genetic composition of the strains.
      Variation between strains was observed in colonization, timing of development of
      clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni
      in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization,
      colonization without disease, colonization with enteritis, colonization with
      hemorrhagic enteritis, and colonization with neurological signs with or without
      enteritis. Virulence gene content of ten sequenced strains was compared in
      silico; virulence gene content of twelve additional strains was compared using a
      C. jejuni pan-genome microarray. Neither total nor virulence gene content
      predicted pathotype; nor was pathotype correlated with multilocus sequence type.
      Each strain was unique with regard to absences of known virulence-related loci
      and/or possession of point mutations and indels, including phase variation, in
      virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice
      showed that expression levels of ninety open reading frames (ORFs) were
      significantly up- or down-regulated in the mouse cecum at least two-fold compared
      to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was
      significantly correlated with the capacity to colonize and cause enteritis in
      C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are
      thus an important determinant of pathotype in C. jejuni strains in this mouse
      model.

PMID- 22960581
TI  - Addition of adult serum improves endothelium-dependent relaxation of organ
      cultured rat mesenteric artery via inhibiting mitochondrial reactive oxygen
      species.
AB  - Organ culture of blood vessels is a useful technique to investigate the long-term
      effects of drugs. Organ culture in a serum-free condition is so far the best way
      to maintain differentiated cell function. However some functional changes may
      occur from freshly isolated blood vessel (fresh) presumably due to lack of some
      key factors for vascular homeostasis in the medium. We investigated the long-term
      effects of addition of adult rat serum on acetylcholine-induced endothelium
      dependent relaxation (EDR). Rat isolated mesenteric arteries were cultured for 3
      days without (0% serum) or with 3% serum. In 0% serum, EDR was significantly
      impaired from fresh, whereas sodium nitroprusside-induced relaxation of smooth
      muscle didn't change. Addition of 3% serum significantly normalized the impaired
      EDR. Acute treatment with N-acetyl-l-cysteine or a mitochondrial inhibitor,
      rotenone normalized the impaired EDR in 0% serum. Mitochondrial superoxide
      production increased in the endothelium with 0% serum, which was normalized by 3%
      serum. Mitochondrial membrane potential increased in the endothelium with 0%
      serum, which was not normalized by 3% serum. In summary, the increased
      endothelial mitochondrial membrane potential in 0% serum may lead to
      mitochondrial reactive oxygen species (ROS) production and subsequent impairment
      of EDR. Addition of adult serum normalized the impaired EDR in part through
      inhibiting the increased mitochondrial ROS but not the membrane potential.

PMID- 22960584
TI  - Transition from gavage to nipple feeding for preterm infants with
      bronchopulmonary dysplasia.
AB  - BACKGROUND: The transition from gavage to nipple feeding is difficult for preterm
      infants with bronchopulmonary dysplasia because of tachypnea and hypoxemia from
      chronic respiratory distress. OBJECTIVE: The aim of this study was to test the
      hypothesis that preterm infants with bronchopulmonary dysplasia who transitioned
      from gavage to nipple feeding with the semidemand method would achieve nipple
      feeding sooner and be discharged from hospital sooner than control infants who
      received standard care. METHODS: Forty-two infants were randomized to the control
      condition and 44 to the experimental protocol. Mean gestational ages and birth
      weights were 25 +/- 1.5 weeks and 784 g for controls and 25 +/- 1.4 weeks and 787
      g for experimental infants. Control infants received standard care that included
      gradual increases in the number of nipple to gavage feedings per day.
      Experimental infants received the semidemand method that used infant behavioral
      and cardiorespiratory signs to regulate frequency, length, and volume of nipple
      feedings. General linear model procedures were used to compare study groups.
      RESULTS: Experimental infants achieved nipple feeding at M = 5.9 +/- 0.7 days
      compared with control infants, M = 12.3 +/- 0.8 (p < .0001). Length of
      hospitalization was not significantly different between groups. DISCUSSION: The
      semidemand method significantly shortened the time for infants to attain nipple
      feeding in a manner taking their respiratory distress into consideration.

PMID- 22960585
TI  - Reliability of the postpartum depression screening scale in the neonatal
      intensive care unit.
AB  - BACKGROUND: Rates of postpartum depression have been found to be significantly
      higher in mothers of infants in the neonatal intensive care unit (NICU) than the
      general population estimate of 10%-15%, making routine screening for these
      mothers essential. OBJECTIVES: The aim of this study was to examine the
      reliability (internal consistency) and construct validity of the Postpartum
      Depression Screening Scale with a sample of mothers of infants in the NICU.
      METHODS: A total of 111 (40% of eligible) mothers participated in the study.
      Mothers completed a brief demographic questionnaire and the screening scale at 14
      or greater days postpartum. Estimates of internal consistency were evaluated
      using Cronbach's coefficient alpha. RESULTS: On the basis of the scale total
      score, 52% of mothers had a positive screen and an additional 30% received a
      score indicating that they were at-risk. Reliability estimates were consistent
      with previous research and indicate excellent internal consistency for the total
      score and adequate to good internal reliability for subscales scores. The
      coefficient alpha for total score equaled .95, and alpha for subscale scores
      ranged from .72 (Anxiety/Insecurity) to .89 (Suicidal Thoughts). Interscale
      correlations were consistently lower than subscale reliability estimates
      (coefficient alpha) and were lower than subscale-to-total score correlations,
      suggesting initial support for the proposed structure of the scale for mothers in
      the NICU. DISCUSSION: Most of this sample of mothers experienced significant
      symptoms of postpartum depression. The Postpartum Depression Screening Scale is a
      promising tool for screening mothers with infants in the NICU. Additional
      research is necessary to better understand the construct and predictive validity
      of scores among these mothers. Current and future research will contribute to the
      routine use of scale as a screening tool in this environment.

PMID- 22960586
TI  - A pilot study: fluid intake and bacteriuria in nursing home residents in southern
      Taiwan.
AB  - BACKGROUND: The significance of bacteriuria or urinary tract infection in
      incontinent residents and the association with fluid intake has not been explored
      fully. OBJECTIVE: The aim of this study was to test whether or not increasing
      fluid intake changed the occurrence of bacteriuria in incontinent residents in
      nursing homes between baseline and 6-week follow-up. METHODS: A quasiexperimental
      study with pretest and posttest design was conducted in six nursing homes in
      Kaohsiung, Taiwan. A 6-week increasing fluid regimen (n = 44) was tested against
      the maintenance group (n = 30). The intake and output checklist was used to
      record residents' fluid intake, and bacteriuria was confirmed by a positive urine
      culture. RESULTS: The prevalence of asymptomatic bacteriuria was 29.7% at
      baseline and 17.6% at the 6-week follow-up. Despite higher percentage of
      reduction in bacteriuria noted in the increasing group (15.9% vs. 6.7%),
      increasing fluid intake to reduce the occurrence of bacteriuria was not
      statistically supported. DISCUSSION: Adequate amount of fluid intake,
      participants' characteristics, and components of a fluid regimen are major
      cautions in interpreting the preliminary results. Fluid intake could be the least
      harmful and the cheapest method to reduce susceptibility for bacteriuria.
      Combining behavioral approaches such as improving access to fluid or scheduled
      toileting may be beneficial in reducing the occurrence of bacteriuria in
      incontinent elders in nursing homes.

PMID- 22960587
TI  - An internet coping skills training program for youth with type 1 diabetes: six
      month outcomes.
AB  - BACKGROUND: Managing Type 1 diabetes (T1D) during adolescence can be challenging,
      and there is a need for accessible interventions to help adolescents cope with
      diabetes-related stress. OBJECTIVES: The aim of this study was to compare an
      Internet coping skills training (TEENCOPE) intervention to an Internet
      educational intervention (Managing Diabetes) for adolescents with T1D. Moderators
      of program efficacy were evaluated. METHODS: The study was a multisite clinical
      trial (n = 320) with data collected at baseline, 3 months, and 6 months. Data
      were collected on the primary outcomes of physiologic (A1C) and psychosocial
      (quality of life) and on the secondary outcomes of behavioral (self-management)
      and psychosocial (stress, coping self-efficacy, social competence, family
      conflict) variables consistent with the conceptual framework. Data were analyzed
      using mixed-model analyses with an intent-to-treat approach. RESULTS: There were
      no significant between-group treatment effects 6 months postintervention on
      primary outcomes. The Managing Diabetes youth showed a significant increase in
      social competence compared to the TEENCOPE youth. There were significant time
      effects for TEENCOPE (decreased stress and increased coping) and Managing
      Diabetes (improved diabetes quality of life). DISCUSSION: Youth with T1D
      transitioning to adolescence may need both structured diabetes education and
      coping skills to improve health outcomes. There may be a higher potential to
      reach adolescents with Type 1 diabetes of varying race and ethnicity via Internet
      interventions.

PMID- 22960588
TI  - Antiemetic effectiveness and nausea and vomiting incidence during capecitabine
      and oxaliplatin chemotherapy.
AB  - BACKGROUND: Capecitabine and oxaliplatin (XELOX) chemotherapy causes nausea and
      vomiting, despite adequate administration of antiemetics. Furthermore, specific
      risk factors that increase this risk are not elucidated. OBJECTIVE: To appraise
      the effectiveness of antiemetics to prevent XELOX-induced nausea and vomiting.
      METHODS: This was a single-center, prospective, cohort study. Patients were
      recruited on the day of chemotherapy and received follow-up after 5 days to
      assess nausea and vomiting and use of antiemetics. Patients were assessed for
      nausea and vomiting control and clinical endpoints of complete response, complete
      protection, and complete control. Multivariate logistic regression was used to
      evaluate the risk factors. RESULTS: Mean age of the 156 patients analyzed was 60
      years (SD = 9.0) with 88 men (56.4%) and 68 women (43.6%). Patient proportions
      achieving complete response (87.8%), complete protection (80.8%), and complete
      control (62.8%) within 24 hours after chemotherapy declined throughout the follow
      up period to 76.9%, 64.7%, and 48.7%, respectively. Patients with fewer than
      three risk factors (odds ratio [OR] = 3.13, p = .006), those receiving
      oxaliplatin less than 100 mg/m (OR = 3.23, p = .009) and capecitabine less than
      1,500 mg/m (OR = 5.00, p = .04), were more likely to achieve complete response.
      CONCLUSIONS: An unacceptably high proportion of patients receiving XELOX were
      identified as being unable to attain adequate control of nausea because of
      inadequate usage of delayed antiemetic prophylaxis. Clinicians should be aware of
      the chemotherapy-induced nausea and vomiting patterns in this subgroup of
      patients on XELOX and tailor appropriate management plans. Incorporation of
      delayed antiemetics to existing institutional guidelines for chemotherapy-induced
      nausea and vomiting management may improve patients' tolerance of XELOX.

PMID- 22960589
TI  - The prevalence of employed nurses identified or enrolled in substance use
      monitoring programs.
AB  - BACKGROUND: For over 100 years, nurses' particular work conditions have been
      anecdotally associated with increases in substance abuse. Reasons include job
      related stress and easy access to medications. Current research has suggested
      that prevalence of nurses with substance use problems is actually similar to, if
      not less than, that seen in the general population. However, given nurses'
      proximity to critical patient care, the potential threat to public health, as
      well as the current shortage of practitioners and problems related to retention,
      the lack of research on the effectiveness of the two existing treatment protocols
      (disciplinary and alternative-to-discipline [ATD]) is a pressing issue of concern
      to the nursing profession. OBJECTIVES: The aims of this study were to estimate
      the 1-year prevalence of employed nurses requiring an intervention for substance
      use problems in the United States and the 1-year prevalence of nurses enrolled in
      substance abuse monitoring programs and to compare the sum total of nurses
      identified in disciplinary and alternative programs with the general population.
      METHODS: This was a balanced stratified sampling design study. Measurements
      included the National Council of State Boards of Nursing 2010 Survey of
      Regulatory Boards Disciplinary Actions on Nurses, the 2009 annual reports of
      alternative programs, the 2008 National Sample Survey of Registered Nurses, and
      the 2009 National Survey on Drug Use and Health. RESULTS: The 2009 1-year
      prevalence of employed nurses identified with substance use problems in the
      United States and its territories was 17,085 or 0.51% of the employed nursing
      population. The 1-year prevalence of nurses newly enrolled in substance abuse
      monitoring programs in the United States and its territories was 12,060 or 0.36%.
      Although every National Council of State Boards of Nursing jurisdiction has a
      disciplinary monitoring program, only 73% (n = 43) of these jurisdictions have
      alternative programs. Despite this, on average, alternative programs had nearly
      75% more new enrollees (9,715) when compared with disciplinary programs (2,345).
      The prevalence of nurses identified with a substance use problem requiring an
      intervention (and likely treatment) is lower than the prevalence of those who
      report receiving substance abuse treatment in the general population (0.51% vs.
      1.0%). CONCLUSIONS: The ATD programs potentially have a greater impact on
      protecting the public than disciplinary programs because ATD programs identify
      and/or enroll more nurses with substance use problems, thereby initially removing
      more nurses with substance use problems from direct patient care.

PMID- 22960590
TI  - Efficacy of physical exercise intervention on mobility and physical functioning
      in older people with dementia: a systematic review.
AB  - Numerous trials have shown that physical activity and exercise training have
      beneficial effects in general older populations. However, few have studied its
      effectiveness among people with dementia. The aim of this systematic review is to
      examine the efficacy of trials using a rigorous randomised, controlled design and
      including physical activity or exercise as a major component of intervention on
      the physical functioning, mobility and functional limitations of people with
      dementia. We found 20 randomised controlled trials that included a total of 1378
      participants. Of these, only three were of high methodological quality, and six
      of moderate quality. Nevertheless, these studies consistently show that intensive
      physical rehabilitation enhances mobility and, when administered over a long
      period, may also improve the physical functioning of patients with dementia.

PMID- 22960591
TI  - Effects of resveratrol on longevity, cognitive ability and aging-related
      histological markers in the annual fish Nothobranchius guentheri.
AB  - Aging research was hindered because of the long lifespan of available
      vertebrates. Annual fishes of Nothobranchius have become a new model organism for
      aging studies. Resveratrol, a natural plant-derived chemical, prolongs lifespan
      in many animals. Here we used the wild strain of N. guentheri, which has the mean
      lifespan of 12months, to detect the effects of resveratrol on the longevity,
      cognitive ability and aging-related histological markers. Our results showed that
      the pharmaceutical treatment of resveratrol prolonged the lifespan of N.
      guentheri but did not affect their body size. Three behavioral assays for
      cognitive ability and locomotor activity demonstrated that the resveratrol
      treated fish exhibited the higher rate of performances than the fish in the
      control group. Further data indicated that resveratrol not only had the property
      of protecting N. guentheri from neurodegeneration, but retarded the aging-related
      histological markers in lipofuscin formation and in the expression of senescence
      associated beta-galactosidase activity.

PMID- 22960592
TI  - PPARgamma and stress: implications for aging.
AB  - Complex interactions link psychological stress and aging - stress generally
      promotes aging processes, and conversely, aging can contribute to stress
      dysregulation. Stress and aging have remarkably similar effects on brain. Both
      induce neuroinflammation and alter neuronal metabolism and activity, which to
      varying extents are causally-linked to the development of stress and aging
      pathology. As such, induction of one or more of these brain disturbances by
      either stress or aging could predispose for the development of dysfunction in the
      other. Notably, peroxisome proliferator-activated receptor gamma (PPARgamma) is
      expressed in brain regions that regulate both stress and aging (e.g.,
      hippocampus) and can act to prevent the consequences of aging and stress on the
      brain. In addition, PPARgamma agonists reduce the physiological stress response
      itself. Thus, PPARgamma may represent a critical mechanistic link between brain
      aging and stress that could hold therapeutic potential for the prevention and
      treatment of age-related cognitive and mood disorders.

PMID- 22960593
TI  - Aging-associated inflammation in healthy Japanese individuals and patients with
      Werner syndrome.
AB  - Minor inflammation-driven aging (inflammaging) has been proposed to explain human
      aging mechanism. To study the inflammatory condition associated with normal human
      aging, highly sensitive CRP (hsCRP) was examined in the sera collected from 217
      healthy Japanese individuals aged between 1 and 100years and 41 mutation-proven
      Japanese Werner syndrome (WS) patients. The serum hsCRP was assayed by ELISA. The
      serum hsCRP level increased significantly (p<0.001) with normal aging from both
      sexes. The serum hsCRP was significantly elevated in WS (mean+/-SE: 11.0+/
      1.6MUg/ml) compared with age-matched normal population (1.3+/-0.3MUg/ml, p<0.001)
      and normal elderly population ages between 71 and 100years (4.2+/-0.7MUg/ml,
      p<0.001). Both normal aging and WS were associated with minor inflammation that
      can be evaluated by serum hsCRP. WS may be a good candidate to study
      inflammaging.

PMID- 22960594
TI  - Letter to the editor on "regulation of HOXA9 activity by predominant expression
      of DACH1 against C/EBPalpha and GATA-1 in myeloid leukemia with MLL-AF9".

PMID- 22960595
TI  - Imaging translation in single cells using fluorescent microscopy.
AB  - The regulation of translation provides a mechanism to control not only the
      abundance of proteins, but also the precise time and subcellular location that
      they are synthesized. Much of what is known concerning the molecular basis for
      translational control has been gleaned from experiments (e.g., luciferase assays
      and polysome analysis) that measure average changes in the protein synthesis of a
      population of cells, however, mechanistic insights can be obscured in ensemble
      measurements. The development of fluorescent microscopy techniques and reagents
      has allowed translation to be studied within its cellular context. Here we
      highlight recent methodologies that can be used to study global changes in
      protein synthesis or regulation of specific mRNAs in single cells. Imaging of
      translation has provided direct evidence for local translation of mRNAs at
      synapses in neurons and will become an important tool for studying translational
      control.

PMID- 22960596
TI  - Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast
      cancer cells via activation of JNK/CHOP/DR5 signaling pathway.
AB  - Simvastatin (SVA) was shown to up-regulate expression of death receptor-5 (DR5),
      CCAAT/enhancer binding protein homologous protein (CHOP) and phosphorylated c-Jun
      N-terminal kinase (pJNK) in human breast cancer cell lines. siRNA knockdown of
      DR5, CHOP or JNK significantly blocked SVA-induced apoptosis, demonstrating the
      importance of JNK/CHOP/DR5 signaling pathway in SVA-induced apoptosis. Exogenous
      addition of either mevalonate or geranylgeranyl pyrophosphate (GGPP) inhibited
      SVA activation of JNK/CHOP/DR5 pro-apoptotic pathway, indicating that activation
      of JNK/CHOP/DR5 pro-apoptotic pathway is dependent on SVA inhibition of 3-hydroxy
      3-methylglutaryl Coenzyme A (HMG-CoA) reductase and its intermediate GGPP. Data
      provide novel insight into better understanding the anticancer mechanisms of SVA.

PMID- 22960597
TI  - Stochastic modeling of stem-cell dynamics with control.
AB  - Tissue development and homeostasis are thought to be regulated endogenously by
      control loops that ensure that the numbers of stem cells and daughter cells are
      maintained at desired levels, and that the cell dynamics are robust to
      perturbations. In this paper we consider several classes of stochastic models
      that describe stem/daughter cell dynamics in a population of constant size, which
      are generalizations of the Moran process that include negative control loops that
      affect differentiation probabilities for stem cells. We present analytical
      solutions for the steady-state expectations and variances of the numbers of stem
      and daughter cells; these results remain valid for non-constant cell populations.
      We show that in the absence of differentiation/proliferation control, the number
      of stem cells is subject to extinction or overflow. In the presence of linear
      control, a steady state may be maintained but no tunable parameters are available
      to control the mean and the spread of the cell population sizes. Two types of
      nonlinear control considered here incorporate tunable parameters that allow
      specification of the expected number of stem cells and also provide control over
      the size of the standard deviation. We show that under a hyperbolic control law,
      there is a trade-off between minimizing standard deviations and maintaining the
      system robustness against external perturbations. For the Hill-type control, the
      standard deviation is inversely proportional to the Hill coefficient of the
      control loop. Biologically this means that ultrasensitive response that is
      observed in a number of regulatory loops may have evolved in order to reduce
      fluctuations while maintaining the desired population levels.

PMID- 22960598
TI  - Ubiquitylation and degradation of elongating RNA polymerase II: the last resort.
AB  - During its journey across a gene, RNA polymerase II has to contend with a number
      of obstacles to its progression, including nucleosomes, DNA-binding proteins, DNA
      damage, and sequences that are intrinsically difficult to transcribe. Not
      surprisingly, a large number of elongation factors have evolved to ensure that
      transcription stalling or arrest does not occur. If, however, the polymerase
      cannot be restarted, it becomes poly-ubiquitylated and degraded by the
      proteasome. This process is highly regulated, ensuring that only RNAPII molecules
      that cannot otherwise be salvaged are degraded. In this review, we describe the
      mechanisms and factors responsible for the last resort mechanism of
      transcriptional elongation. This article is part of a Special Issue entitled: RNA
      polymerase II Transcript Elongation.

PMID- 22960600
TI  - Localization of the ATP-sensitive K(+) channel regulatory subunits SUR2A and
      SUR2B in the rat brain.
AB  - ATP-sensitive K(+) (K(ATP)) channel subunits SUR2A and SUR2B in the rat brain
      were investigated by RT-PCR assay, western blot analysis, in situ hybridization
      histochemistry, and immunohistochemical staining. The results show that the mRNA
      and protein of SUR2A and SUR2B are expressed in whole rat brain extracts and
      selected regions. SUR2 mRNA is widely expressed in many neurons and glial cells
      as revealed by in situ hybridization histochemistry. Immunohistochemical staining
      shows SUR2A to be widely expressed in neurons of the brain, especially in the
      large pyramidal neurons and their main dendrites in the neocortex and in the
      Purkinje cells of the cerebellar cortex. In contrast to SUR2A, SUR2B is potently
      expressed in small cells in the corpus callosum and cerebellar white matter, but
      is also weakly expressed in some neurons. Double immunostaining shows SUR2B to be
      localized in astrocytes and oligodendrocytes, while SUR2A is only localized in
      oligodendrocytes. These results suggest that SUR2A might be mainly a regulatory
      subunit of the K(ATP) channel in most neurons and part of oligodendrocytes, while
      SUR2B might be mainly a regulatory subunit of the K(ATP) channel in astrocytes,
      oligodendrocytes, and some neurons.

PMID- 22960601
TI  - Comparison of rescue strategies in lamivudine-resistant patients with chronic
      hepatitis B.
AB  - Lamivudine (LAM) resistance now poses a major problem in the management of
      patients with chronic hepatitis B virus (HBV) infection. We retrospectively
      collected clinical data on chronic HBV-infected patients who had developed LAM
      resistance under de novo LAM monotherapy and subsequently took nucleos(t)ide
      analogs as rescue strategy in our hospital. From initiation of rescue therapies
      to January 2012, incidence of antiviral drug resistance was 23.67%, 18%, 6.94%
      and 0% (P=0.007) in the group of switching to adefovir dipivoxil (ADV)
      monotherapy, switching to entecavir (ETV) monotherapy, adding on ADV and
      switching to combination of ADV and ETV. At month 12, the median levels of serum
      HBV DNA were respectively 9300IU/mL, 4648IU/mL, 2054IU/mL and 100IU/mL (P<0.001),
      and the cumulative rates of serum ALT normalization were respectively 75%, 84%,
      93% and 100% (P=0.003). Additionally, the strategy of switching to ADV
      monotherapy induced more single rtA181T mutations. In conclusion, switching to
      ADV monotherapy has been widely used in real-world clinical practice in China,
      however, due to the high incidence of drug resistance, switching to neither ADV
      nor ETV monotherapy is optimal when LAM resistance occurs; combination of ADV and
      ETV is most effective, whereas the strategy of adding on ADV is rational for most
      of LAM-resistant Chinese patients with chronic hepatitis B.

PMID- 22960599
TI  - TFIIB-related factors in RNA polymerase I transcription.
AB  - Eukaryotic RNA polymerases (Pol) I, II, III and archaeal Pol use a related set of
      general transcription factors to recognize promoter sequences and recruit Pol to
      promoters and to function at key points in the transcription initiation
      mechanism. The TFIIB-like general transcription factors (GTFs) function during
      several important and conserved steps in the initiation pathway for Pols II, III,
      and archaeal Pol. Until recently, the mechanism of Pol I initiation seemed
      unique, since it appeared to lack a GTF paralogous to the TFIIB-like proteins.
      The surprising recent discovery of TFIIB-related Pol I general factors in yeast
      and humans highlights the evolutionary conservation of transcription initiation
      mechanisms for all eukaryotic and archaeal Pols. These findings reveal new roles
      for the function of the Pol I GTFs and insight into the function of TFIIB-related
      factors. Models for Pol I transcription initiation are reexamined in light of
      these recent findings. This article is part of a Special Issue entitled:
      Transcription by Odd Pols.

PMID- 22960602
TI  - Selection pressure on the hepatitis B virus pre-S/S and P open reading frames in
      Tongan subjects with a chronic hepatitis B virus infection.
AB  - Identification of the full repertoire of hepatitis B virus (HBV) peptides that
      are presented to CD8+ T cells by common HLA class I alleles will be useful for
      designing immunotherapies for chronic hepatitis B. One hundred and seventy five
      cloned sequences containing the pre-S/S and P open reading frames (ORF) of the
      HBV were obtained from serum HBV-DNA of HBeAg-positive (n=4) and HBeAg-negative
      (inactive healthy carriers (IHC), n=16) Tongan subjects with an inactive chronic
      HBV infection. In addition, 34 and 32 sequences were obtained 5.2+/-1.4 (mean+/
      SD) years apart from eight subjects. PAML was used to identify codons in the pre
      S/S and P ORFs that were under positive selection pressure (omega>1). The number
      of non-synonymous substitutions in these codons was compared in IHC who were
      homozygous for either HLA-B*4001 (n=9) or HLA-B*5602 (n=7), and who were either
      positive (n=6) or negative (n=10) for HLA-A*02. 34 codons in the pre-S/S and 11
      codons in the P ORFs were under positive selection pressure. There was a higher
      number of non-synonymous substitutions in these codons in HBeAg-negative versus
      HBeAg-positive subjects in the P (p=0.02) but not the pre-S/S (p=0.64) ORF. There
      was no association between any HLA class I allele and non-synonymous
      substitutions in these codons. There was no increase in positive selection
      pressure on the pre-S/S and P ORFs with time. In conclusion, we could not find
      HLA class I-restricted selection pressure on any pre-S/S or P ORF amino acid;
      raising the possibility that peptide-based immunotherapies for chronic hepatitis
      B may not require peptides from these ORFs.

PMID- 22960603
TI  - Hepatitis B virus basal core promoter mutations A1762T/G1764A are associated with
      genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive
      Chinese patients.
AB  - The present study was aimed to obtain baseline information of basal core promoter
      A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192
      HBeAg-positive chronically-infected Chinese patients, who were potential
      candidates for antiviral treatment. The detection of these mutations (including
      minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity
      for minor mutant subpopulations identification was confirmed by clone sequencing.
      Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV
      identified by routine tests in our laboratory. The A1762T/G1764A or G1896A
      mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125,
      61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be
      more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs.
      20.22% (18/89), P<0.0001]. There is no statistically significant link between
      G1896A and genotypes. The emergence of A1762T/G1764A mutations was also found to
      be associated with an older age, an elevated ALT/AST level, and a lower HBsAg
      level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36),
      P<0.0001]. In conclusion, HBV basal core promoter mutations A1762T/G1764A are
      associated with genotype C and a low serum HBsAg level in chronically-infected
      HBeAg-positive Chinese patients.

PMID- 22960605
TI  - Changes in regional activity of the psoas major and quadratus lumborum with
      voluntary trunk and hip tasks and different spinal curvatures in sitting.
AB  - STUDY DESIGN: Cross-sectional controlled laboratory study. OBJECTIVES: To
      investigate the function of discrete regions of psoas major (PM) and quadratus
      lumborum (QL) with changes in spinal curvature and hip position. BACKGROUND:
      Anatomically discrete regions of PM and QL may have differential function on the
      lumbar spine, based on anatomical and biomechanical differences in their moment
      arms between fascicles within each muscle. METHODS: Fine-wire electrodes were
      inserted with ultrasound guidance into PM fascicles arising from the transverse
      process (PM-t) and vertebral body (PM-v) and anterior (QL-a) and posterior (QL-p)
      layers of QL. Recordings were made on 9 healthy participants, who performed 7
      tasks with maximal voluntary efforts and adopted 3 sitting postures that involved
      different spinal curvatures and hip angles. RESULTS: Activity of PM-t was greater
      during trunk extension than flexion, whereas activity of PM-v was greater during
      hip flexion than trunk efforts. Activity of QL-p was greater during trunk
      extension and lateral flexion, whereas QL-a showed greater activity during
      lateral flexion. During sitting tasks, PM-t was more active when sitting with a
      short lordosis than a flat (less extended) lumbar spine posture, whereas PM-v was
      similarly active in both sitting postures. CONCLUSION: Activity of PM-t was more
      affected by changes in position of the lumbar spine than the hip, whereas PM-v
      was more actively involved in the movement of the hip rather than that of the
      lumbar spine. Moreover, from its anatomy, PM-t has a combined potential to
      extend/lordose the lumbar spine and flex the hip, at least in a flexed-hip
      position.

PMID- 22960604
TI  - Germinal center kinases in immune regulation.
AB  - Germinal center kinases (GCKs) participate in a variety of signaling pathways
      needed to regulate cellular functions including apoptosis, cell proliferation,
      polarity and migration. Recent studies have shown that GCKs are participants in
      both adaptive and innate immune regulation. However, the differential activation
      and regulatory mechanisms of GCKs, as well as upstream and downstream signaling
      molecules, remain to be fully defined. It remains unresolved whether and how GCKs
      may cross-talk with existing signaling pathways. This review stresses the
      progresses in research of GCKs relevant to the immune system.

PMID- 22960606
TI  - Two-dimensional gel electrophoresis revealed antipsychotic drugs induced protein
      expression modulations in C6 glioma cells.
AB  - The efficacy and side effects of long-term administration of antipsychotic drugs
      (APDs) may be attributed to drug-induced change in protein expression in brain
      cells. Glial cells are non-neuronal cells that can provide nutrients and
      physiological support to neuronal cells. Glial cells are believed to participate
      in neurotransmission, neurons' early development, and guiding migration of
      neurons. Accumulated clinical data also indicate relationships between
      disturbance of glial cells' function and various psychotic diseases including
      schizophrenia. We used two-dimensional gel electrophoresis coupled with MALDI
      TOF/TOF mass spectrometry protein identification to analyze differentially
      expressed proteins in haloperidol-, risperidone-, and clozapine-treated C6 glioma
      cells. We found that the expression of pericentrin, glial fibrillary acidic
      protein, Rho GDP-dissociation inhibitor 1, anionic trypsin-1, peroxiredoxin-1,
      and parvalbumin were regulated by each of the three APDs. Western blot analysis
      supported the findings. Real-time quantitative PCR detected changed
      transcriptions of those proteins. Protein and gene expression of N-cadherin in C6
      cells were affected by haloperidol and clozapine but not risperidone. In
      addition, regulatory effects of clozapine on the glyceraldehyde 3-phosphate
      dehydrogenase gene were observed in C6 cells. This may be the first study to
      uncover how APD-modulated genes may cause protein expression changes and affect
      ARHGDIA-mediated regulation of Rho GTPase family proteins in glial cells.

PMID- 22960607
TI  - NMDA GluN2B receptors involved in the antidepressant effects of curcumin in the
      forced swim test.
AB  - The antidepressant-like effect of curcumin, a major active component of Curcuma
      longa, has been previously demonstrated in the forced swimming test. However, the
      mechanism of this beneficial effect on immobility scores, which is used to
      evaluate antidepressants, remains largely uncharacterized. The present study
      attempts to investigate the effects of curcumin on depressive-like behavior with
      a focus upon the possible contribution of N-methyl-D-aspartate (NMDA) subtype
      glutamate receptors in this antidepressant-like effect of curcumin. Male mice
      were pretreated with specific receptor antagonists to different NMDA receptor
      subtypes such as CPP, NVP-AAM077 and Ro25-6981 as well as to a partial NMDA
      receptor agonist, D-cycloserine (DCS), prior to administration of curcumin to
      observe the effects on depressive behavior as measured by immobility scores in
      the forced swim test. We found that pre-treatment of mice with CPP, a broad
      spectrum competitive NMDA receptor antagonist, blocked the anti-immobility effect
      of curcumin, suggesting the involvement of the glutamate-NMDA receptors. While
      pretreatment with NVP-AAM077 (the GluN2A-preferring antagonist) did not affect
      the anti-immobility effect of curcumin, Ro25-6981 (the GluN2B-preferring
      antagonist) was found to prevent the effect of curcumin in the forced swimming
      test. Furthermore, pre-treatment with a sub-effective dose of DCS potentiated the
      anti-immobility effect of a sub-effective dose of curcumin in the forced swimming
      test. Taken together, these results suggest that curcumin shows antidepressant
      like effects in mice and the activation of GluN2B-containing NMDARs is likely to
      play a predominate role in this beneficial effect. Therefore, the antidepressant
      like effect of curcumin in the forced swim test may be mediated, at least in
      part, by the glutamatergic system.

PMID- 22960608
TI  - Chronic restraint stress in rats causes sustained increase in urinary
      corticosterone excretion without affecting cerebral or systemic oxidatively
      generated DNA/RNA damage.
AB  - Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common
      mechanism underlying accelerated aging in psychological stress states and mental
      disorders. In the present study, we measured the urinary excretion of
      corticosterone and markers of systemic oxidative stress on nucleic acids, 8-oxo
      7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8
      oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably
      collect 24h urine samples, the full 3-week restraint stress paradigm was
      performed in metabolism cages. We further determined frontal cortex and
      hippocampal levels of oxidatively generated nuclear DNA damage, as measured by
      oxoguanine DNA glycosylase and formamidopyrimidine DNA glycosylase sensitive
      sites detected by the comet assay, as well as the expression of genes involved in
      DNA repair (Ogg1 and Nudt1) and inflammation (Ccl2 and Tnf). The metabolism cage
      housing in itself did not significantly influence a range of biological stress
      markers. In the restraint stress group, there was a sustained 2.5 fold increase
      in 24h corticosterone excretion from day 2 after stress initiation. However,
      neither whole-body nor cerebral measures of nucleic acid damage from oxidation
      were affected by stress. In contrast, cerebral DNA repair enzymes exhibited a
      general trend towards an induction, which was significant for hippocampal Nudt1.
      The results and their implications for stress sensitivity and resilience are
      discussed.

PMID- 22960609
TI  - Enhanced neuroprotective effect of fish oil in combination with quercetin against
      3-nitropropionic acid induced oxidative stress in rat brain.
AB  - While the beneficial effects of fish oil (FO) supplements on the central nervous
      system function are well established, few findings have led to the hypothesis
      that long term n-3 polyunsaturated fatty acid (n-3 PUFA) supplements at higher
      doses render the membranes more susceptible to lipid peroxidation. Hence recent
      studies suggest the use of dietary antioxidants as adjuncts with n-3 fatty acids
      to effectively improve the clinical outcome in neurological disorders. In the
      present investigation, we examined the hypothesis, if enrichment of FO with
      quercetin (a natural flavonoid) can provide a higher degree of neuroprotection
      and tested the same in a 3-nitropropionic acid (NPA) rat model. Growing male rats
      administered with NPA (25 mg/kg bw/d, i.p. 4 days) were provided either with FO
      (2 mL/kg bw), or Q (25mg/kg bw) or FO+Q for 14 days. NPA elicited marked
      oxidative stress in brain (striatum and cerebellum) as evidenced by significantly
      enhanced ROS, malondialdehyde, protein carbonyls and nitric oxide levels.
      Although varying degree of protection was evident among FO or Q groups, complete
      normalization of oxidative markers ensued only among FO+Q rats. Further, FO+Q
      combination completely normalized the elevated acetylcholinesterase activity and
      protected against NPA-induced mitochondrial dysfunctions. NPA induced depletion
      of dopamine levels was restored among all groups. Interestingly, NPA induced
      motor deficits were significantly improved among FO+Q rats. However, further
      studies are necessary to understand the mechanism/s by which FO enrichment with Q
      provides higher degree of protection. Nevertheless, our findings clearly suggest
      that the use of natural phytochemicals with moderate doses of FO may provide
      better neuroprotection and higher therapeutic advantage in the prevention or
      treatment of neurodegenerative diseases like Huntington's disease.

PMID- 22960610
TI  - Nerve growth factor stimulation of ERK1/2 phosphorylation requires both p75NTR
      and alpha9beta1 integrin and confers myoprotection towards ischemia in C2C12
      skeletal muscle cell model.
AB  - The functions of nerve growth factor (NGF) in skeletal muscles physiology and
      pathology are not clear and call for an updated investigation. To achieve this
      goal we sought to investigate NGF-induced ERK1/2 phosphorylation and its role in
      the C2C12 skeletal muscle myoblasts and myotubes. RT-PCR and western blotting
      experiments demonstrated expression of p75(NTR), alpha9beta1 integrin, and its
      regulator ADAM12, but not trkA in the cells, as also found in gastrocnemius and
      quadriceps mice muscles. Both proNGF and betaNGF induced ERK1/2 phosphorylation,
      a process blocked by (a) the specific MEK inhibitor, PD98059; (b) VLO5, a MLD
      disintegrin with relative selectivity towards alpha9beta1 integrin; and (c)
      p75(NTR) antagonists Thx-B and LM-24, but not the inactive control molecule
      backbone Thx. Upon treatment for 4 days with either anti-NGF antibody or VLO5 or
      Thx-B, the proliferation of myoblasts was decreased by 60-70%, 85-90% and 60-80%
      respectively, indicative of trophic effect of NGF which was autocrinically
      released by the cells. Exposure of myotubes to ischemic insult in the presence of
      betaNGF, added either 1h before oxygen-glucose-deprivation or concomitant with
      reoxygenation insults, resulted with about 20% and 33% myoprotection, an effect
      antagonized by VLO5 and Thx-B, further supporting the trophic role of NGF in
      C2C12 cells. Cumulatively, the present findings propose that proNGF and betaNGF
      induced ERK1/2 phosphorylation in C2C12 cells by functional cooperation between
      p75(NTR) and alpha9beta1 integrin, which are involved in myoprotective effects of
      autocrine released NGF. Furthermore, the present study establishes an important
      trophic role of alpha9beta1 in NGF-induced signaling in skeletal muscle model,
      resembling the role of trkA in neurons. Future molecular characterization of the
      interactions between NGF receptors in the skeletal muscle will contribute to the
      understanding of NGF mechanism of action and may provide novel therapeutic
      targets.

PMID- 22960611
TI  - Twin screw granulation: steps in granule growth.
AB  - The present work focuses on the study of the progression of granules in different
      compartments along the length of screws in a twin screw granulator (TSG). The
      effects of varying powder feed rate; liquid to solid ratio and viscosity of
      granulation liquid on properties of granules was studied. The bigger granules
      produced at the start of the process were found to change in terms of size, shape
      and strength along the screw length at all the conditions investigated. The
      granules became more spherical and their strength increased along the screw
      length. Tracer granules were also introduced in order to understand the role of
      kneading and conveying elements in the TSG. The kneading elements promoted
      consolidation and breakage while the conveying elements led to coalescence,
      breakage and some consolidation. The results presented here help to provide a
      qualitative and quantitative understanding of the twin screw granulation process.

PMID- 22960612
TI  - d-Cycloserine administration does not affect neurocognition in concurrent cocaine
      and nicotine-dependent volunteers.
AB  - Neurocognitive impairment is a well-documented consequence of long-term, repeated
      cocaine exposure and has been identified as an important target of treatment.
      Thus, this study sought to determine whether the N-methyl-d-aspartate (NMDA)
      partial agonist, d-cycloserine could improve neurocognitive performance in a
      sample of 27 long-term, high dose cocaine dependent individuals who were not
      seeking treatment at the time of enrollment in the study. This double-blind,
      placebo-controlled study evaluated whether a single dose of 0 or 50mg of d
      cycloserine would enhance performance on measures of attention/information
      processing speed, episodic memory, and executive/frontal lobe functioning
      relative to test performance at baseline. The results revealed that d-cycloserine
      did not modulate neurocognition in this cohort, though there are a number of
      factors that may have mitigated the effects of d-cycloserine in this particular
      study. The negative findings notwithstanding, the current study serves as a
      springboard for future investigations that will examine whether other medications
      that can modulate neurocognition in cocaine-dependent study participants.

PMID- 22960613
TI  - Severe and recurrent interface hemorrhage after endothelial keratoplasty.
AB  - PURPOSE: To report the occurrence and management of recurrent hemorrhage after
      Descemet stripping endothelial keratoplasty (DSEK) in a patient with pseudophakic
      bullous keratopathy. METHODS: An 84-year-old Chinese woman on two oral
      antiplatelet drugs underwent DSEK in her left eye. Preoperative best-corrected
      visual acuity was 20/30 OD and 14/200 OS. Intraoperative bleeding was noted from
      the iris root. Surgery was completed uneventfully, and interface was thoroughly
      irrigated in the end. Slit lamp examination on the first postoperative day showed
      a dense interface hemorrhage and an intraocular pressure of 24 mm Hg. Repeat
      interface irrigation was carried out on postoperative day 4, but the hemorrhage
      appeared again on the following day. Donor lenticule was well apposed to the
      corneal stroma, and visual acuity was hand motions in the operated eye. No
      further surgical interventions were performed. Corticosteroid eye drops were
      continued four times a day in the operated eye, and the patient was advised
      weekly follow-up. RESULTS: Over the next 4 weeks, the interface blood gradually
      started to clear from the central cornea. At the end of 4 months postoperatively,
      the interface hemorrhage disappeared completely. A final best-corrected visual
      acuity of 20/80 was achieved. Specular microscopy revealed an endothelial cell
      density of 1375 cells/mm2. CONCLUSIONS: Interface hemorrhage is a known
      complication after DSEK surgery. Recurrent hemorrhage may be expected in patients
      on oral antiplatelet treatment. In cases without associated graft dislocation,
      conservative management can still result in good visual outcome.

PMID- 22960614
TI  - Imatinib mesylate (Gleevec) induced unilateral optic disc edema.
AB  - PURPOSE: Imatinib mesylate (Gleevec) is a chemotherapy medication developed to
      treat chronic myelogenous leukemia as well as gastrointestinal stromal tumors
      (Savage, N Engl J Med 2002;346:683-93). Ocular side effects are commonly reported
      with the use of imatinib mesylate, such as periorbital edema and epiphora. More
      serious ocular side effects, such as optic disc edema, are rarely reported. CASE
      REPORT: This case is of a patient who presented with monocular painless loss of
      vision in the left eye from a previously documented 20/20 to 20/70 shortly after
      starting treatment with imatinib mesylate. RESULTS: Every aspect of the ocular
      presentation and clinical history were addressed to unveil the cause of the disc
      edema. After ruling out all other causes, the patient was later diagnosed with
      unilateral optic disc edema as a related side effect of the toxicity from
      imatinib mesylate. CONCLUSIONS: The properties of imatinib mesylate and the
      possible etiology of secondary optic disc edema are discussed. This study aims to
      highlight the importance of systemic medications review for possible etiology of
      ocular disease as well as the multidisciplinary approach to managing oncology
      patients with ocular side effects.

PMID- 22960615
TI  - Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens
      performance.
AB  - PURPOSE: To report on the development and validation of a short form of the
      Contact Lens Dry Eye Questionnaire (the CLDEQ-8) to enable it to reflect status
      of and change in overall opinion ("opinion") of soft contact lenses (SCLs).
      METHODS: Item reduction for the CLDEQ was achieved by correlation with overall
      opinion of SCLs at follow-up visits in a sample of 38 SCL wearers at one academic
      clinical site. The CLDEQ-8 score (frequency plus late day intensity of dryness,
      discomfort, and "blurry vision"; frequency of "closing eyes to rest them" and
      "removing CLs to relieve discomfort") was then tested in 379 SCL wearers in a
      multicenter study with analysis stratified by opinion ratings at baseline and 2
      weeks postrandomization to new silicone hydrogel SCLs. The sum of CLDEQ-8 scores
      (maximum 37) was correlated with opinion by Spearman's rank correlation
      coefficient and analyzed for change in opinion by analysis of variance (ANOVA).
      RESULTS: The CLDEQ-8 scores in the validation sample were highly correlated with
      habitual baseline opinion (-0.44, p < 0.0001) and responsive to change in opinion
      postrandomization (-0.58, p < 0.0001). Baseline CLDEQ-8 scores by opinion status
      were as follows: Fair: 17.4 +/- 8.7, Good 13.7 +/- 6.4, Very Good 9.1 +/- 4.7,
      and Excellent 6.4 +/- 3.7 (ANOVA, F = 291.1, p < 0.0001). After 2 weeks, change
      in CLDEQ-8 scores by improvement status was as follows: Much Improved: -16.7 +/-
      10.0, Unchanged: -2.3 +/- 5.0, to Much Worse +8.5 +/- 5.8 (ANOVA, F = 16.5, p <
      0.001). CONCLUSIONS: The CLDEQ-8 score significantly reflected baseline status
      and change in overall opinion after refitting with two types of silicone
      hydrogels. The CLDEQ-8 score is a valid outcome measure in SCL clinical trials to
      reflect opinion of SCLs.

PMID- 22960616
TI  - Beware of "old" Horner syndrome.
AB  - PURPOSE: Chronic Horner syndrome is a rare clinical condition, the etiology of
      which often remains undiscovered. A patient is presented with an 8-year history
      of Horner syndrome who was diagnosed with multiple cervical artery dissections.
      CASE REPORT: A 42-year-old woman presented to our emergency department with a
      severe occipital headache that woke her up from sleep 3 days earlier. She had a
      history of headaches and recalled one in particular dating back to 2003. At that
      time, she sought medical attention at general practitioner's office because of
      the terrible headache and a noticeable disparity of her pupils. She was told that
      she had miosis of the right pupil. The examination conducted in 2011 revealed
      Horner syndrome with right miosis and ptosis. A four-vessel cerebral angiography
      revealed an occlusion of the right internal carotid artery. The morphology of
      stenosis and pseudoaneurysm of C1 segment of left internal carotid artery, as
      well as a pseudoaneurysm of V3/V4 junction of left vertebral artery indicated a
      probable dissective etiology. CONCLUSIONS: This case illustrates that Horner
      syndrome with a chronic presentation can be as potentially dangerous as its acute
      counterpart and should be judiciously investigated.

PMID- 22960617
TI  - Medical decision-making capacity and cataract surgery.
AB  - BACKGROUND: Medical decision making has evolved from a paternalistic, "doctor
      knows best system" to one of shared decision making between health care providers
      and patients. Shared decision making involves informed consent related to the
      proposed health care options and medical decision-making capacity by patients.
      Adults aged 90 and older are the fastest growing segment of the US population.
      Dementia prevalence increases dramatically among this group. Dementia may affect
      the ability of patients to participate in shared decision making. CASE REPORT:
      The case of a 91-year-old female rehabilitation inpatient with mild cognitive
      impairment, cataracts, and macular degeneration is presented. The case highlights
      key issues of informed decision making and medical decision-making capacity
      related to cataract surgery. Video examples of the assessment of cognitive and
      medical decision-making capacity are presented.

PMID- 22960618
TI  - Single cell oil production from low-cost substrates: the possibility and
      potential of its industrialization.
AB  - Currently, single cell oils (SCO) attract much attention because of their bi
      function as a supplier of functional oils and feedstock for biodiesel production.
      However, high fermentation costs prevent their further application, and the
      possibility and potential of their industrialization is suspected. Therefore,
      various low-cost, hydrophilic and hydrophobic substrates were utilized for SCO
      production. Of these substrates, lignocellulosic biomass, which is the most
      available and renewable source in nature, might be an ideal raw material for SCO
      production. Although many reviews on SCO have been published, few have focused on
      SCO production from low-cost substrates or evaluated the possibility and
      potential of its industrialization. Therefore, this review mainly presents
      information on SCO and its production using low-cost substrates and mostly
      focuses on lignocellulosic biomass. Finally, the possibility and potential of SCO
      industrialization is evaluated.

PMID- 22960619
TI  - Different isoforms of starch-synthesizing enzymes controlling amylose and
      amylopectin content in rice (Oryza sativa L.).
AB  - Starch, composed of amylose and amylopectin, greatly influences rice cooking and
      textural quality, which in turn is controlled by various isoforms of several
      enzymes. Activity of one or more isoforms of starch-synthesizing enzymes results
      in various forms of starch structure based on the amylopectin chain length and
      average external, internal and core chain length distribution and hence results
      in varying physicochemical and cooking quality. Since the synthesis of starch is
      highly complex, it is crucial but essential to understand its biosynthetic
      pathway, starch structure and effects on the physicochemical properties that
      control eating and cooking quality, and alongside conduct research on gene/QTL
      mapping for use in marker-assisted selection (MAS) with a view to improve and
      select cultivars with most desirable range and class of rice starch properties.
      This article presents the updates on current understanding of the coordination
      among various enzymes/isoforms towards rice starch synthesis in endosperm and
      their effect on rice grain physicochemical, cooking and eating qualities. The
      efforts in identifying regions responsible for these enzymes by mapping the
      gene/QTLs have provided a glimpse on their association with physicochemical and
      cooking properties of rice and, hence, improvement is possible by modifying the
      allelic pattern, resulting in down or nil regulation of a particular enzyme. The
      clear understanding of the tissue specific coordination between enzyme isoforms
      and their subsequent effect in controlling eating and cooking properties will
      enhance the chances to manipulate them for getting desired range of amylose
      content (AC) and gelatinization temperature (GT) in improved cultivars through
      combining desired alleles through MAS.

PMID- 22960620
TI  - Recent advances in two-phase partitioning bioreactors for the treatment of
      volatile organic compounds.
AB  - Biological processes are considered to be the most cost-effective technology for
      the off-gas treatment of volatile organic compounds (VOC) at low concentrations.
      Two-phase partitioning bioreactors (TPPBs) emerged in the early 1990s as
      innovative multiphase systems capable of overcoming some of the key limitations
      of traditional biological technologies such as the low mass transfer rates of
      hydrophobic VOCs and microbial inhibition at high VOC loading rates. Intensive
      research carried out in the last 5 years has helped to provide a better
      understanding of the mass transfer phenomena and VOC uptake mechanisms in TPPBs,
      which has significantly improved the VOC biodegradation processes utilizing this
      technology platform. This work presents an updated state-of-the-art review on the
      advances of TPPB technology for air pollution control. The most recent insights
      regarding non-aqueous phase (NAP) selection, microbiology, reactor design,
      mathematical modeling and case studies are critically reviewed and discussed.
      Finally, the key research issues required to move towards the development of
      efficient and stable full-scale VOC biodegradation processes in TPPBs are
      identified.

PMID- 22960621
TI  - The Ume6-Sin3-Rpd3 complex regulates ATG8 transcription to control autophagosome
      size.
AB  - The vast majority of studies addressing the induction of autophagy have focused
      upon cytoplasmic aspects of its regulation. Recently, we have started to expand
      our knowledge regarding the nuclear events of autophagic induction. Many
      autophagy-related genes are transcriptionally upregulated upon induction of
      autophagy, but only in a limited number of cases do we know the pathways leading
      to this upregulation. Few transcription factors have been implicated in
      controlling autophagy genes in yeast. However, many of the ATG genes show some
      level of transcriptional induction upon starvation. Now, we show that
      transcription of ATG8 is repressed under growing conditions by the Ume6-Sin3-Rpd3
      complex.

PMID- 22960622
TI  - Developmental expression and subcellular distribution of synaptotagmin 11 in rat
      hippocampus.
AB  - Synaptotagmins are required for Ca(2+)-dependent membrane-trafficking in either
      neuronal synaptic vesicles or cellular membranes. Previous reports suggested that
      the synaptotagmin 11 (syt11) gene is involved in the development of schizophrenia
      based on the genomic analysis of patients. Parkin protein binds to the C2 domains
      of Syt11 which leads to the polyubiquitination of Syt11. However, where and how
      Syt11 performs its role in the brain is largely unknown. Here, we report that
      Syt11 is expressed mainly in the brain. In addition, exogenously expressed Syt11
      in HEK293 cells can form higher molecular weight complex via its transmembrane
      domain. Also, Syt11 is targeted to both dendrite and axon compartments.
      Immunocytochemistry showed that Syt11 is juxtaposed to postsynaptic markers in
      both excitatory and inhibitory synapses. Both neuroligin 1 and 2, which are
      postsynaptic cell adhesion molecules and differentially induce excitatory and
      inhibitory presynapses, respectively, recruit Syt11 in neuron coculture.
      Immunogold electron microscopy analysis revealed that Syt11 exists mainly in
      presynaptic neurotransmitter vesicles and plasma membrane, and rarely in
      postsynaptic sites. These results suggest that Syt11 may contribute to the
      regulation of neurotransmitter release in the excitatory and inhibitory
      presynapses, and postsynapse-targeted membrane trafficking in dendrites.

PMID- 22960623
TI  - Intra-axonal calcium changes after axotomy in wild-type and slow Wallerian
      degeneration axons.
AB  - Calcium accumulation induces the breakdown of cytoskeleton and axonal
      fragmentation in the late stages of Wallerian degeneration. In the early stages
      there is no evidence for any long-lasting, extensive increase in intra-axonal
      calcium but there does appear to be some redistribution. We hypothesized that
      changes in calcium distribution could have an early regulatory role in axonal
      degeneration in addition to the late executionary role of calcium. Schmidt
      Lanterman clefts (SLCs), which allow exchange of metabolites and ions between the
      periaxonal and extracellular space, are likely to have an increased role when
      axon segments are separated from the cell body, so we used the oxalate
      pyroantimonate method to study calcium at SLCs in distal stumps of transected
      wild-type and slow Wallerian degeneration (Wld(S)) mutant sciatic nerves, in
      which Wallerian degeneration is greatly delayed. In wild-type nerves most SLCs
      show a step gradient of calcium distribution, which is lost at around 20% of SLCs
      within 3mm of the lesion site by 4-24h after nerve transection. To investigate
      further the association with Wallerian degeneration, we studied nerves from
      Wld(S) rats. The step gradient of calcium distribution in Wld(S) is absent in
      around 20% of the intact nerves beneath SLCs but 4-24h following injury, calcium
      distribution in transected axons remained similar to that in uninjured nerves. We
      then used calcium indicators to study influx and buffering of calcium in injured
      neurites in primary culture. Calcium penetration and the early calcium increase
      in this system were indistinguishable between Wld(S) and wild-type axons.
      However, a significant difference was observed during the following hours, when
      calcium increased in wild-type neurites but not in Wld(S) neurites. We conclude
      that there is little relationship between calcium distribution and the early
      stages of Wallerian degeneration at the time points studied in vivo or in vitro
      but that Wld(S) neurites fail to show a later calcium rise that could be a cause
      or consequence of the later stages of Wallerian degeneration.

PMID- 22960624
TI  - Centrally acting oximes in reactivation of tabun-phosphoramidated AChE.
AB  - Organophosphates (OP) inhibit acetylcholinesterase (AChE, EC 3.1.1.7), both in
      peripheral tissues and central nervous system (CNS), causing adverse and
      sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine
      (ACh). The currently used therapy, focusing on the reactivation of inhibited
      AChE, is limited to peripheral tissues because commonly used quaternary
      pyridinium oxime reactivators do not cross the blood brain barrier (BBB) at
      therapeutically relevant levels. A directed library of thirty uncharged oximes
      that contain tertiary amine or imidazole protonable functional groups that should
      cross the BBB as unionized species was tested as tabun-hAChE conjugate
      reactivators along with three reference oximes: DAM (diacetylmonoxime), MINA
      (monoisonitrosoacetone), and 2-PAM. The oxime RS150D [N-((1-(3-(2
      ((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4
      yl)methyl)benzamide] was highlighted as the most promising reactivator of the
      tabun-hAChE conjugate. We also observed that oximes RS194B [N-(2-(azepan-1
      yl)ethyl)-2-(hydroxyimino)acetamide] and RS41A [2-(hydroxyimino)-N-(2-(pyrrolidin
      1-yl)ethyl)acetamide], which emerged as lead uncharged reactivators of
      phosphylated hAChE with other OPs (sarin, cyclosarin and VX), exhibited only
      moderate reactivation potency for tabun inhibited hAChE. This implies that
      geometry of oxime access to the phosphorus atom conjugated to the active serine
      is an important criterion for efficient reactivation, along with the chemical
      nature of the conjugated moiety: phosphorate, phosphonate, or phosphoramidate.
      Moreover, modification of the active center through mutagenesis enhances the
      rates of reactivation. The phosphoramidated-hAChE choline-binding site mutant
      Y337A showed three-times enhanced reactivation capacity with non-triazole
      imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide
      derivative (RS194B) than with 2PAM.

PMID- 22960625
TI  - A novel reciprocal loop between microRNA-21 and TGFbetaRIII is involved in
      cardiac fibrosis.
AB  - Cardiac fibrosis is characterized by aberrant proliferation of cardiac
      fibroblasts and exaggerated deposition of extracellular matrix (ECM) in the
      myocardial interstitial, and ultimately impairs cardiac function. It is still
      controversial whether microRNA-21 (miR-21) participates in the process of cardiac
      fibrosis. Our previous study confirmed that transforming growth factor beta
      receptor III (TGFbetaRIII) is a negative regulator of TGF-beta pathway. Here, we
      aimed to decipher the relationship between miR-21 and TGFbetaRIII in the
      pathogenic process of myocardial fibrosis. We found that TGF-beta1 and miR-21
      were up-regulated, whereas TGFbetaRIII was down-regulated in the border zone of
      mouse hearts in response to myocardial infarction. After transfection of miR-21
      into cardiac fibroblasts, TGFbetaRIII expression was markedly reduced and
      collagen content was increased. And, luciferase results confirmed that
      TGFbetaRIII was a target of miR-21. It suggests that up-regulation of miR-21
      could increase the collagen content and at least in part through inhibiting
      TGFbetaRIII. Conversely, we also confirmed that overexpression of TGFbetaRIII
      could inhibit the expression of miR-21 and reduce collagen production in
      fibroblasts. Further studies showed that overexpression of TGFbetaRIII could also
      deactivate TGF-beta1 pathway by decreasing the expression of TGF-beta1 and
      phosphorylated-Smad3 (p-Smad3). TGF-beta1 has been proven as a positive regulator
      of miR-21. Taken together, we found a novel reciprocal loop between miR-21 and
      TGFbetaRIII in cardiac fibrosis caused by myocardial infarction in mice, and
      targeting this pathway could be a new strategy for the prevention and treatment
      of myocardial remodeling.

PMID- 22960627
TI  - The filling of powdered herbs into two-piece hard capsules using hydrogenated
      cotton seed oil as lubricant.
AB  - The aim of this work was to investigate the plug formation and filling properties
      of powdered herbal leaves using hydrogenated cotton seed oil as an alternative
      lubricant. In a first step, unlubricated and lubricated herbal powders were
      studied on a small scale using a plug simulator, and low-force compression
      physics and parameterization techniques were used to narrow down the range in
      which the optimum amount of lubricant required would be found. In a second step
      these results were complemented with investigations into the flow properties of
      the powders based on packing (tapping) experiments to establish the final optimum
      lubricant concentration. Finally, capsule filling of the optimum formulations was
      undertaken using an instrumented tamp filling machine. This work has shown that
      hydrogenated cotton seed oil can be used advantageously for the lubrication of
      herbal leaf powders. Stickiness as observed with magnesium stearate did not
      occur, and the optimum lubricant concentration was found to be less than that
      required for magnesium stearate. In this work, lubricant concentrations of 1% or
      less hydrogenated cotton seed oil were required to fill herbal powders into
      capsules on the instrumented tamp-filling machine. It was found that in principle
      all powders could be filled successfully, but that for some powders the use of
      higher compression settings was disadvantageous. Relationships between the
      particle size distributions of the powders, their flow and consolidation as well
      as their filling properties could be identified by multivariate statistical
      analysis. The work has demonstrated that a combination of the identification of
      plug formation and powder flow properties is helpful in establishing the optimum
      lubricant concentration required using a small quantity of powder and a powder
      plug simulator. On an automated tamp-filling machine, these optimum formulations
      produced satisfactory capsules in terms of coefficient of fill weight variability
      and capsule weight.

PMID- 22960626
TI  - Animal models of Parkinson's disease: vertebrate genetics.
AB  - Parkinson's disease (PD) is a complex genetic disorder that is associated with
      environmental risk factors and aging. Vertebrate genetic models, especially mice,
      have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are
      capable of showing a broad range of phenotypes and, coupled with their conserved
      genetic and anatomical structures, provide unparalleled molecular and
      pathological tools to model human disease. These models used in combination with
      aging and PD-associated toxins have expanded our understanding of PD
      pathogenesis. Attempts to refine PD animal models using conditional approaches
      have yielded in vivo nigrostriatal degeneration that is instructive in ordering
      pathogenic signaling and in developing therapeutic strategies to cure or halt the
      disease. Here, we provide an overview of the generation and characterization of
      transgenic and knockout mice used to study PD followed by a review of the
      molecular insights that have been gleaned from current PD mouse models. Finally,
      potential approaches to refine and improve current models are discussed.

PMID- 22960628
TI  - Redox redux.

PMID- 22960629
TI  - Toxicologic evaluations of DHA-rich algal oil in rats: developmental toxicity
      study and 3-month dietary toxicity study with an in utero exposure phase.
AB  - DHA-rich algal oil ONC-T18, tested for subchronic, reproductive, and
      developmental toxicity in the rat, did not produce any significant toxicologic
      manifestations. Based on the absence of maternal or developmental toxicity at any
      dosage level, a dosage level of 2000 mg/kg/day was considered to be the no
      observed adverse-effect level (NOAEL) for maternal toxicity and embryo/fetal
      development when DHA-rich algal oil was administered orally by gavage to pregnant
      Crl:CD(SD) rats during gestation days 6-19. In a dietary combined one
      generation/90-day reproductive toxicity study in rats, the NOAEL for F0 male and
      female and F1 male systemic toxicity was considered to be 50,000 ppm (highest
      concentration administered) and 25,000 ppm for F1 female systemic toxicity
      (higher mean body weight, body weight gain, and food consumption). F0
      reproductive performance values, estrous cycle length, gestation length, or the
      process of parturition, and the numbers of former implantation sites and
      unaccounted-for sites were unaffected by algal oil exposure. Postnatal survival
      and developmental parameters in the F1 generation were unaffected by algal oil
      exposure at all dietary concentrations. There were no neurotoxic effects noted at
      any algal oil exposure level. The results support the safety of DHA-rich algal
      oil for its proposed use in food.

PMID- 22960630
TI  - Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its
      effect on GLUT4 translocation in streptozotocin-induced diabetic rats.
AB  - Plumbago zeylanica L. root is widely used in Indian medicine to treat diabetes
      mellitus. The aim of the present investigation was to evaluate the antidiabetic
      effects of plumbagin isolated from P. zeylanica L. root and its effect on GLUT4
      translocation in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg b wt) was
      orally administered to STZ-induced diabetic rats for 28 days. An oral glucose
      tolerance test was performed on 21st day. The effect of plumbagin on body weight,
      blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen,
      plasma enzymes (SGOT, SGPT and ALP) and carbohydrate metabolism enzymes (glucose
      6-phosphatase, fructose-1,6-bisphosphatase and hexokinase) were investigated.
      GLUT4 mRNA and protein expression in skeletal muscles were also studied.
      Plumbagin significantly reduced the blood glucose and significantly altered all
      other biochemical parameters to near normal. Further, plumbagin increased the
      activity of hexokinase and decreased the activities of glucose-6-phosphatase and
      fructose-1,6-bisphosphatase significantly in treated diabetic rats. Enhanced
      GLUT4 mRNA and protein expression were observed in diabetic rats after treatment
      with plumbagin. The results indicated that plumbagin enhanced GLUT4 translocation
      and contributed to glucose homeostasis. It could be further probed for use as a
      drug to treat diabetes.

PMID- 22960631
TI  - Do environments in infancy moderate the association between stress and
      inflammation in adulthood? Initial evidence from a birth cohort in the
      Philippines.
AB  - Chronic inflammation is a potentially important pathway through which
      psychosocial stressors increase risk for cardiovascular disease. However, prior
      research on stress and inflammation has been conducted almost exclusively in high
      income, industrialized populations with low levels of infectious disease. In this
      study we test the hypothesis that psychosocial stressors are associated with
      elevated concentrations of C-reactive protein (CRP) among young adults in the
      Philippines (n=1622), who have grown up in an ecological and epidemiological
      setting that differs substantially from that of the US. In addition, we apply a
      developmental, ecological perspective to consider whether microbial and
      nutritional environments in infancy alter patterns of association between
      stressors and CRP. Data come from the Cebu Longitudinal Health and Nutrition
      Survey, a prospective cohort study that began collecting data in 1983-1984 when
      participants were in utero. A series of regression models indicate trends toward
      significant interactions between perceived stress and environmental factors in
      infancy, including exposure to animal feces, season of birth, and birth weight.
      Parental absence in childhood was a significant predictor of CRP in adulthood in
      interaction with exposure to animal feces in infancy. Positive associations
      between stressors and CRP were only evident for individuals with lower levels of
      microbial exposure in infancy, or lower birth weight. These results suggest that
      early environments influence the development of inflammatory phenotypes in ways
      that moderate sensitivity to psychosocial stressors in adulthood, and they
      underscore the value of a comparative, developmental approach to research on
      social environments, inflammation, and disease.

PMID- 22960632
TI  - RING-between-RINGs--keeping the safety on loaded guns.

PMID- 22960633
TI  - Structural basis for Arl3-specific release of myristoylated ciliary cargo from
      UNC119.
AB  - Access to the ciliary membrane for trans-membrane or membrane-associated proteins
      is a regulated process. Previously, we have shown that the closely homologous
      small G proteins Arl2 and Arl3 allosterically regulate prenylated cargo release
      from PDEdelta. UNC119/HRG4 is responsible for ciliary delivery of myristoylated
      cargo. Here, we show that although Arl3 and Arl2 bind UNC119 with similar
      affinities, only Arl3 allosterically displaces cargo by accelerating its release
      by three orders of magnitude. Crystal structures of Arl3 and Arl2 in complex with
      UNC119a reveal the molecular basis of specificity. Contrary to previous
      structures of GTP-bound Arf subfamily proteins, the N-terminal amphipathic helix
      of Arl3.GppNHp is not displaced by the interswitch toggle but remains bound on
      the surface of the protein. Opposite to the mechanism of cargo release on
      PDEdelta, this induces a widening of the myristoyl binding pocket. This leads us
      to propose that ciliary targeting of myristoylated proteins is not only dependent
      on nucleotide status but also on the cellular localization of Arl3.

PMID- 22960635
TI  - Che-ating death: CHE1/AATF protects from p53-mediated apoptosis.
AB  - The tumour suppressor p53 directs cells towards different fates depending on the
      cell type and the stimulus. The decision to direct a cell towards apoptosis
      rather than cell-cycle arrest or senescence has important implications for tumour
      suppression in normal cells and drug response in tumour cells. Cells that undergo
      senescence and growth arrest can persist and contribute to organismal ageing
      (Campisi, 2005), or they can contribute to tumour relapse (Jackson et al, 2012).
      In this issue of The EMBO Journal, Hopker et al (2012) show in a comprehensive
      study that the RNA PolII binding protein CHE1/AATF is a factor that determines
      the fate of cells that have activated the p53 pathway.

PMID- 22960634
TI  - Dimerization and direct membrane interaction of Nup53 contribute to nuclear pore
      complex assembly.
AB  - Nuclear pore complexes (NPCs) fuse the two membranes of the nuclear envelope (NE)
      to a pore, connecting cytoplasm and nucleoplasm and allowing exchange of
      macromolecules between these compartments. Most NPC proteins do not contain
      integral membrane domains and thus it is largely unclear how NPCs are embedded
      and anchored in the NE. Here, we show that the evolutionary conserved nuclear
      pore protein Nup53 binds independently of other proteins to membranes, a property
      that is crucial for NPC assembly and conserved between yeast and vertebrates. The
      vertebrate protein comprises two membrane binding sites, of which the C-terminal
      domain has membrane deforming capabilities, and is specifically required for de
      novo NPC assembly and insertion into the intact NE during interphase.
      Dimerization of Nup53 contributes to its membrane interaction and is crucial for
      its function in NPC assembly.

PMID- 22960636
TI  - Low-hanging fruit: targeting Brdt in the testes.

PMID- 22960637
TI  - TRP channel blamed for burning cold after a tropical fish meal.

PMID- 22960639
TI  - Birthing histone mRNAs by CSR-1 section.

PMID- 22960638
TI  - Alternative 3'-end processing of long noncoding RNA initiates construction of
      nuclear paraspeckles.
AB  - Paraspeckles are unique subnuclear structures built around a specific long
      noncoding RNA, NEAT1, which is comprised of two isoforms produced by alternative
      3'-end processing (NEAT1_1 and NEAT1_2). To address the precise molecular
      processes that lead to paraspeckle formation, we identified 35 paraspeckle
      proteins (PSPs), mainly by colocalization screening with a fluorescent protein
      tagged full-length cDNA library. Most of the newly identified PSPs possessed
      various putative RNA-binding domains. Subsequent RNAi analyses identified seven
      essential PSPs for paraspeckle formation. One of the essential PSPs, HNRNPK,
      appeared to affect the production of the essential NEAT1_2 isoform by negatively
      regulating the 3'-end polyadenylation of the NEAT1_1 isoform. An in vitro 3'-end
      processing assay revealed that HNRNPK arrested binding of the CPSF6-NUDT21 (CFIm)
      complex in the vicinity of the alternative polyadenylation site of NEAT1_1. In
      vitro binding assays showed that HNRNPK competed with CPSF6 for binding to
      NUDT21, which was the underlying mechanism to arrest CFIm binding by HNRNPK. This
      HNRNPK function led to the preferential accumulation of NEAT1_2 and initiated
      paraspeckle construction with multiple PSPs.

PMID- 22960640
TI  - Targeting mitochondrial oxidative metabolism as an approach to treat heart
      failure.
AB  - Heart failure is a major cause of morbidity and mortality in the world. Cardiac
      energy metabolism, specifically fatty acid and glucose metabolism, is altered in
      heart failure and has been implicated as a contributing factor in the impaired
      heart function observed in heart failure patients. There is emerging evidence
      demonstrating that correcting these changes in energy metabolism by modulating
      mitochondrial oxidative metabolism may be an effective treatment for heart
      failure. Promising strategies include the downregulation of fatty acid oxidation
      and an increased coupling of glycolysis to glucose oxidation. Carnitine palmitoyl
      transferase I (CPT1), fatty acid beta-oxidation enzymes, and pyruvate
      dehydrogenase kinase (PDK) are examples of metabolic targets for the treatment of
      heart failure. While targeting mitochondrial oxidative metabolism is a promising
      strategy to treat heart failure, further studies are needed to confirm the
      potential beneficial effect of modulating these metabolic targets as an approach
      to treating heart failure. This article is part of a Special Issue entitled:
      Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and
      Contraction.

PMID- 22960641
TI  - The emerging multiple roles of nuclear Akt.
AB  - Akt is a central player in the signal transduction pathways activated in response
      to many growth factors, hormones, cytokines, and nutrients and is thought to
      control a myriad of cellular functions including proliferation and survival,
      autophagy, metabolism, angiogenesis, motility, and exocytosis. Moreover,
      dysregulated Akt activity is being implicated in the pathogenesis of a growing
      number of disorders, including cancer. Evidence accumulated over the past 15
      years has highlighted the presence of active Akt in the nucleus, where it acts as
      a fundamental component of key signaling pathways. For example, nuclear Akt
      counteracts apoptosis through a block of caspase-activated DNase:
      deoxyribonuclease and inhibition of chromatin condensation, and is also involved
      in cell cycle progression control, cell differentiation, mRNA: messenger RNA
      export, DNA repair, and tumorigenesis. In this review, we shall summarize the
      most relevant findings about nuclear Akt and its functions.

PMID- 22960643
TI  - The effect of aging on dopamine release and metabolism during sevoflurane
      anesthesia in rat striatum: an in vivo microdialysis study.
AB  - We have previously reported that halothane anesthesia increases extracellular
      concentrations of dopamine (DA) metabolites in rat striatum using in vivo
      microdialysis techniques. Aging induces many changes in the brain, including
      neurotransmission. However, the relationship between aging and changes in
      neurotransmitter release during inhalational anesthesia has not been fully
      investigated. The aim of the present investigation was to evaluate the effect of
      sevoflurane on methamphetamine (MAPT)-induced DA release and metabolism in young
      and middle-aged rats. Male Sprague-Dawley rats were implanted with a
      microdialysis probe into the right striatum. The probe was perfused with a
      modified Ringer's solution and 40MUl of dialysate was directly injected to an
      HPLC every 20min. Rats were administered saline, the same volume of 2mgkg(-1)
      MAPT intraperitoneally, or 5MUM MAPT locally perfused. After treatments, the rats
      were anesthetized with 1% or 3% sevoflurane for 1h. Sevoflurane anesthesia
      significantly increased the extracellular concentration of DA only in middle-aged
      rats (52-weeks-old). In young rats (8-weeks-old), sevoflurane significantly
      enhanced MAPT-induced DA when administered both intraperitoneally and perfused
      locally, whereas no significant additive interaction was found in middle-aged
      rats. These results suggest that aging changes DA release and metabolism in rat
      brains primarily by decreasing the DA transporter.

PMID- 22960644
TI  - Therapeutic effects of short-term monochromatic infrared energy therapy on
      patients with knee osteoarthritis: a double-blind, randomized, placebo-controlled
      study.
AB  - STUDY DESIGN: Randomized, double-blind, placebo-controlled study. OBJECTIVES: To
      examine the short-term therapeutic effects of monochromatic infrared energy
      (MIRE) on participants with knee osteoarthritis (OA). Patients were assessed
      according to the International Classification of Functioning, Disability and
      Health. BACKGROUND: MIRE is commonly used in therapy for patients with peripheral
      neuropathies. However, research has not focused intensively on the therapeutic
      effects of MIRE in patients with knee OA. METHODS: This study enrolled 73
      participants with knee OA. Participants received six 40-minute sessions of active
      or placebo MIRE treatment (890-nm wavelength; power, 6.24 W; energy density, 2.08
      J/cm2/min; total energy, 83.2 J/cm2) over the knee joints for 2 weeks.
      International Classification of Functioning, Disability and Health-related
      outcomes were collected weekly over 4 weeks using the Knee injury and
      Osteoarthritis Outcome Score, Lysholm Knee Scale, Hospital Anxiety and Depression
      Scale, Multidimensional Fatigue Inventory, Chronic Pain Grade questionnaire,
      World Health Organization Quality of Life-brief version, and OA Quality of Life
      Questionnaire. Data were analyzed by repeated-measures analysis of variance.
      RESULTS: No statistically significant differences were found for the interaction
      of group by time for Knee injury and Osteoarthritis Outcome Score scores,
      including pain, other symptoms, function in daily living, function in sport and
      recreation, and knee-related quality of life. Scores on the Lysholm Knee Scale,
      Hospital Anxiety and Depression Scale, Multidimensional Fatigue Inventory,
      Chronic Pain Grade questionnaire, World Health Organization Quality of Life-brief
      version, and OA Quality of Life Questionnaire also showed no significant
      differences between the 2 groups at any of the 4 follow-up assessments.
      CONCLUSION: Short-term MIRE therapy provided no beneficial effects to body
      functions, activities, participation, and quality of life in patients with knee
      OA.

PMID- 22960645
TI  - Multidrug resistant bacteria isolated from cockroaches in long-term care
      facilities and nursing homes.
AB  - Residents in long-term care facilities and nursing homes have a relative higher
      risk for infections. The nocturnal and filthy habits of cockroaches may be ideal
      disseminators of pathogenic microorganisms in these institutions. This study was
      designed to determine the infestation and vector potential of cockroaches under
      this institutional environment. Cockroaches were collected from 69 long-term care
      facilities and nursing homes in Kaohsiung City. Risk factors related to cockroach
      infestation were determined by questionnaire survey. In addition, bacteria were
      isolated and identified from the alimentary tract and external surface of these
      insects. Antibiotic resistances of these microorganisms were then determined.
      Cockroach infestation was found in 45 (65.2%) institutions and 558 cockroaches
      (119 Periplaneta americana and 439 Blattella germanica) were collected. A
      significant association was found between cockroach infestation and indoor
      environmental sanitation. From 250 adult cockroaches, 38 species of gram-negative
      bacteria, 20 species of glucose non-fermenter bacilli and 6 species of gram
      positive bacteria were isolated. Moreover, antibiotic resistances were found
      among the bacteria isolated. These findings indicate that cockroaches have the
      potential in transmitting pathogenic bacteria with multidrug resistances in long
      term care facilities and nursing homes.

PMID- 22960642
TI  - Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling
      and EC-coupling.
AB  - In cardiac muscle, a number of posttranslational protein modifications can alter
      the function of the Ca(2+) release channel of the sarcoplasmic reticulum (SR),
      also known as the ryanodine receptor (RyR). During every heartbeat RyRs are
      activated by the Ca(2+)-induced Ca(2+) release mechanism and contribute a large
      fraction of the Ca(2+) required for contraction. Some of the posttranslational
      modifications of the RyR are known to affect its gating and Ca(2+) sensitivity.
      Presently, research in a number of laboratories is focused on RyR
      phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by
      reactive oxygen and nitrogen species (ROS/RNS). Both classes of posttranslational
      modifications are thought to play important roles in the physiological regulation
      of channel activity, but are also known to provoke abnormal alterations during
      various diseases. Only recently it was realized that several types of
      posttranslational modifications are tightly connected and form synergistic (or
      antagonistic) feed-back loops resulting in additive and potentially detrimental
      downstream effects. This review summarizes recent findings on such
      posttranslational modifications, attempts to bridge molecular with cellular
      findings, and opens a perspective for future work trying to understand the
      ramifications of crosstalk in these multiple signaling pathways. Clarifying these
      complex interactions will be important in the development of novel therapeutic
      approaches, since this may form the foundation for the implementation of multi
      pronged treatment regimes in the future. This article is part of a Special Issue
      entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism
      and Contraction.

PMID- 22960646
TI  - RFLPs of ITS, ITS1 and hsp70 amplicons and sequencing of ITS1 of recent clinical
      isolates of Kala-azar from India and Bangladesh confirms the association of L.
      tropica with the disease.
AB  - Visceral Leishmaniasis or Kala-azar (KA) is a serious health concern in India. In
      the present study, Restriction Fragment Length Polymorphism (RFLP) of three
      genetic markers viz., Internal Transcribed Spacer (ITS), ITS1 and heat shock
      protein 70 (hsp70) have been employed for typing the clinical isolates [n=15] of
      KA and post Kala-azar Dermal Leishmaniosis (PKDL) collected from India and
      Bangladesh in the period of 2006-2010. Experimentally, ITS, ITS1 and hsp70
      regions of genomes of all the clinical isolates were separately amplified by PCR
      and then digested with restriction enzymes: ITS with Alu1, EcoR1 and Msp1, ITS1
      with Hae III and Rsa1 and hsp70 with Hae III. The resultant fragments were
      analyzed by agarose gel electrophoresis and the RFLP profiles of the clinical
      isolates were compared with that of the WHO reference strains for Leishmania
      donovani (DD8) and Leishmania tropica (K27), respectively. Also, the ITS1 regions
      of all the clinical isolates along with the two WHO reference strains were
      sequenced and a phylogram was constructed to ascertain the extent of similarity
      or dissimilarity. Interestingly, the RFLP profiles of one of the isolates showed
      a significant homology with K27 and the phylogram revealed its closeness with the
      same putting credence to our earlier typing of isolates by RAPD method. This
      observation also supported an earlier report claiming that both the species are
      responsible for KA in India and thus, emphasizes urgent need for thorough
      systematic characterization of the clinical isolates of Indian KA as appropriate
      treatment regime relies primarily on proper diagnosis.

PMID- 22960647
TI  - Infectious keratitis after Boston type 1 keratoprosthesis implantation.
AB  - PURPOSE: To determine the incidence, clinical features, and outcomes of
      infectious keratitis after Boston type 1 keratoprosthesis (Kpro) implantation.
      METHODS: Ten cases of infectious keratitis were identified in a retrospective
      chart review of 105 patients (126 eyes) who received Kpro between November 2004
      and November 2010 at the Cincinnati Eye Institute and were followed for at least
      1 month (range, 1-66 months; mean, 25 months). RESULTS: The incidence was 7.9%.
      Patient diagnoses included 4 chemical injuries, 3 Stevens-Johnson syndrome, 2
      ocular cicatricial pemphigoid, and 1 congenital aniridia. Kpro implantation was
      indicated in 2 eyes for a failed ocular surface and in 8 for penetrating
      keratoplasty failure. Four patients were contact lens intolerant or noncompliant.
      All were on topical vancomycin and moxifloxacin for prophylaxis and 2 were on
      topical amphotericin for prophylaxis. Three infiltrates were culture negative, 5
      were fungal (3 Candida, 1 Fusarium, 1 Dactylaria constricta), and 2 were
      bacterial (Rhodococcus equi and Gram-negative cocci). All patients were managed
      with topical agents and 4 were given an oral antifungal agent. Four patients had
      Kpro removal with therapeutic penetrating keratoplasty and 1 had Kpro
      replacement. At final follow-up, only 2 patients retained their preinfection best
      vision. Risk factors for infectious keratitis included a diagnosis of cicatrizing
      conjunctivitis (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or
      chemical injury) and a history of persistent epithelial defect (P = 0.0003 and
      0.0142, respectively). Contact lens wear, vancomycin use, and a history of
      systemic immunosuppression (or use at the time of infection) were not
      statistically significant risk factors. CONCLUSIONS: Infectious keratitis after
      Kpro can occur even when patients are on vancomycin and a fourth-generation
      fluoroquinolone for prophylaxis. Fungal organisms are a growing cause for
      concern, and we present the details of the first reported case of ocular D.
      constricta. The evolution of our management and prophylaxis strategy for fungal
      keratitis after Kpro implantation is also described.

PMID- 22960649
TI  - Long-term outcome of an unusual haemophilic pseudotumour.
AB  - Haemophilia, a lifelong congenital bleeding disease, is a highly demanding
      disorder, due to the costs of its replacement therapy. In the absence of this
      pivotal treatment, life expectancy and quality of life are deleteriously
      affected. As illustration, we present a 14 years long follow-up of a patient with
      severe haemophilia A, treated sporadically with fresh plasma, cryoprecipitate and
      factor concentrates, who developed a giant iliopsoas pseudotumor. Since he was an
      infant, under on demand therapy with fresh frozen plasma, cryoprecipitate and low
      doses of factor concentrates he presented many spontaneous bleedings, developing
      multiple disabling arthropathies. At the age of 14 years, an iliopsoas hematoma
      occurred, which relapsed several times, developing an iliopsoas pseudotumour.
      After 5 years, sepsis with Klebsiella was diagnosed. A CT scan revealed fistula
      between the pseudotumor and the gut. Under antibiotics, the evolution of sepsis
      improved, but over a period of 10 months 5 episodes of haematemesis and melena,
      followed by one episode of macroscopic haematuria occurred; two months later he
      developed an inguino-crural mass, which fistulized through the abdominal wall. A
      mixt german-romanian team solved the clinical concern. After 108 hospitalization
      days and consumption of 104840 IU factor VIII he left the clinic in good
      condition. One year later, the temporary colostomy with anus praeter was closed.
      The follow-up reveals now, after almost 10 years with favourable outcome, that
      the patient is well, active within his family and profession.

PMID- 22960648
TI  - Endothelial failure after collagen cross-linking with riboflavin and UV-A: case
      report with literature review.
AB  - PURPOSE: To report a case of endothelial decompensation after a collagen cross
      linking (CXL) procedure for keratoconus. METHODS: An 18-year-old boy had CXL for
      keratoconus in the right eye. He developed keratouveitis with generalized corneal
      edema seen 3 weeks after the procedure. Polymerase chain reaction for aqueous
      humor Herpes simplex virus was negative. The patient was treated with topical
      steroids. Specular microscopy revealed mildly reduced density of endothelial
      cells. On follow-up to 6 months, corneal edema increased with the formation of
      epithelial bullae. Penetrating keratoplasty was performed. Possible causes for
      this complication are discussed. RESULTS: Clinical and histopathological analyses
      revealed generalized loss of endothelial cells along with signs of inflammation.
      CONCLUSIONS: Although it is considered very safe, collagen CXL can cause severe
      keratouveitis and endothelial failure.

PMID- 22960650
TI  - Synthesis of multiply deuterated 3- and 21-monosulfates of allo
      tetrahydrocorticosteroids as internal standards for mass spectrometry.
AB  - The accurate analysis of trace components in complex biological matrices requires
      the use of reliable internal standards. For liquid chromatography/mass
      spectrometry analysis, the stable isotope-labeled analogues of the analyte
      molecules are the most appropriate internal standards. In this paper the
      synthesis of the 3- and 21-monosulfates of allo-tetrahydrocorticosteroids labeled
      with four or five deuterium atoms is described. The principal reactions used were
      (1) hydrogen-deuterium exchange reaction of active methylene groups adjacent to 3
      and 11-oxo group of 17,20;20,21-bismethylenedioxy derivatives of 5alpha-3
      ketosteroids and/or 5alpha-11-ketosteroids with NaOD in CH(3)OD followed by
      reduction with NaBD(4), (2) epimerization of the 3beta-hydroxy group into a
      3alpha configuration, (3) sulfation of hydroxy groups at C-3 or C-21 in the
      resulting substrates with sulfur trioxide-trimethylamine complex, and (4) removal
      of 17,20;20,21-bismethylenedioxy groups with hydrogen fluoride in ethanol.
      Isotopic purity was found to be satisfactory by MS, and NMR properties of the new
      compounds were tabulated. The labeled compounds can be used as internal standards
      in liquid chromatography/mass spectrometry assays for clinical and biochemical
      studies.

PMID- 22960651
TI  - Do mollusks use vertebrate sex steroids as reproductive hormones? Part I:
      Critical appraisal of the evidence for the presence, biosynthesis and uptake of
      steroids.
AB  - The consensus view is that vertebrate-type steroids are present in mollusks and
      perform hormonal roles which are similar to those that they play in vertebrates.
      Although vertebrate steroids can be measured in molluscan tissues, a key question
      is 'Are they formed endogenously or they are picked up from their environment?'.
      The present review concludes that there is no convincing evidence for
      biosynthesis of vertebrate steroids by mollusks. Furthermore, the 'mollusk'
      genome does not contain the genes for key enzymes that are necessary to transform
      cholesterol in progressive steps into vertebrate-type steroids; nor does the
      mollusk genome contain genes for functioning classical nuclear steroid receptors.
      On the other hand, there is very strong evidence that mollusks are able to absorb
      vertebrate steroids from the environment; and are able to store some of them (by
      conjugating them to fatty acids) for weeks to months. It is notable that the
      three steroids that have been proposed as functional hormones in mollusks (i.e.
      progesterone, testosterone and 17beta-estradiol) are the same as those of humans.
      Since humans (and indeed all vertebrates) continuously excrete steroids not just
      via urine and feces, but via their body surface (and, in fish, via the gills), it
      is impossible to rule out contamination as the sole reason for the presence of
      vertebrate steroids in mollusks (even in animals kept under supposedly 'clean
      laboratory conditions'). Essentially, the presence of vertebrate steroids in
      mollusks cannot be taken as reliable evidence of either endogenous biosynthesis
      or of an endocrine role.

PMID- 22960652
TI  - A microwave promoted solvent-free approach to steroidal quinolines and their in
      vitro evaluation for antimicrobial activities.
AB  - The preparation of A-ring and D-ring fused steroidal quinolines is described from
      one-pot reaction of steroidal beta-bromovinylaldehydes and arylamines in solvent
      free and catalyst-free condition under microwave irradiation. The antimicrobial
      activities of the compounds were tested by agar diffusion assay and broth macro
      dilution method. Compounds 7a, 7e and 7g-h showed promising in vitro activity
      when tested against fungal pathogen Aspergillus niger whereas compounds 7e-h and
      7j showed promising activity when tested against fungal pathogen Candida
      albicans. Compounds 7c and 7f showed potent inhibition against the growth of Gram
      negative bacteria Pseudomonas aeruginosa and compounds 7e, 7g-h and 7j inhibited
      the growth of tested Gram positive bacteria Bacillus subtilis and Staphylococcus
      aureus.

PMID- 22960653
TI  - An integrated PCR microfluidic chip incorporating aseptic electrochemical cell
      lysis and capillary electrophoresis amperometric DNA detection for rapid and
      quantitative genetic analysis.
AB  - A fully integrated microchip for performing cell lysis, polymerase chain reaction
      (PCR) and quantitative analysis of DNA amplicons in a single step is described
      herein. The chip was built on glass substrate using an indium-tin-oxide (ITO)
      microheater and PDMS engraved microchannels, which integrated an electrochemical
      cell lysis zone, a continuous flow PCR module and capillary electrophoresis
      amperometric detection (CE-AD) system. The total length of the microchannel was
      4625 mm for performing 25 cycles of flow-through PCR and was laid on a handheld
      form factor of 96 * 96 mm(2) area. The key to the fabrication of such a device
      lies in the use of a single medium to carry out different kinds of biochemical
      reactions and hence, a reagentless electrochemical cell lysis protocol was
      integrated on the microchip which was capable of lysing most cell types,
      including difficult to lyse gram positive bacteria. The lysate contained genomic
      DNA from a sample which was proven to be suitable for PCR reactions. Genetic
      analysis was successfully performed on the microchip with purified lambda phage
      genomic DNA and various cell types, including non-tumorigenic MCF-10A and
      tumorigenic MCF-7 human cell lines, gram negative bacteria Escherichia coli
      O157:H7, and gram positive bacteria Bacillus subtilis, at an optimized flow rate
      of 5 MUl min(-1). For the detection of amplicon DNA, a CE-AD system was used,
      with semisolid alkaline agarose within the capillary microchannel to minimize
      interference from cell debris and for efficient resolution of DNA fragments. High
      signal to noise ratio during amperometric detection and the use of online FFT
      filtering protocol enhanced the limit of detection of DNA amplicons. Therefore,
      with a combination of portability, cost-effectiveness and performance, the
      proposed integrated PCR microchip can be used for one step genetic analysis of
      most of the cell types and will enable more accessible healthcare.

PMID- 22960654
TI  - Signaling lymphocyte activation molecule regulates development of colitis in
      mice.
AB  - BACKGROUND & AIMS: Signaling lymphocyte activation molecule (Slamf)1 is a co
      stimulatory receptor on T cells and regulates cytokine production by macrophages
      and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages,
      therefore we investigated whether the receptor affects development of colitis in
      mice. METHODS: We transferred CD45RB(hi) CD4(+) T cells into Rag(-/-) or Slamf1(
      /-)Rag(-/-) mice to induce colitis. We also induced colitis by injecting mice
      with an antibody that activates CD40. We determined the severity of enterocolitis
      based on disease activity index, histology scores, and levels of cytokine
      production, and assessed the effects of antibodies against Slamf1 on colitis
      induction. We quantified migration of monocytes and macrophage to inflamed
      tissues upon induction of colitis or thioglycollate-induced peritonitis and in
      response to tumor necrosis factor-alpha in an air-pouch model of leukocyte
      migration. RESULTS: Colitis was reduced in Slamf1(-/-)Rag(-/-) mice, compared
      with Rag(-/-) mice, after transfer of CD45RB(hi) CD4(+) T cells or administration
      of the CD40 agonist. The numbers of monocytes and macrophages were reduced in
      inflamed tissues of Slamf1(-/-)Rag(-/-) mice, compared with Rag(-/-) mice, after
      induction of colitis and other inflammatory disorders. An antibody that inhibited
      Slamf1 reduced the level of enterocolitis in Rag(-/-) mice. CONCLUSIONS: Slamf1
      contributes to the development of colitis in mice. It appears to indirectly
      regulate the appearance of monocytes and macrophages in inflamed intestinal
      tissues. Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1
      might be a therapeutic target for inflammatory bowel disease.

PMID- 22960655
TI  - Adrenomedullin is up-regulated in patients with pancreatic cancer and causes
      insulin resistance in beta cells and mice.
AB  - BACKGROUND & AIMS: New-onset diabetes in patients with pancreatic cancer is
      likely to be a paraneoplastic phenomenon caused by tumor-secreted products. We
      aimed to identify the diabetogenic secretory product(s) of pancreatic cancer.
      METHODS: Using microarray analysis, we identified adrenomedullin as a potential
      mediator of diabetes in patients with pancreatic cancer. Adrenomedullin was up
      regulated in pancreatic cancer cell lines, in which supernatants reduced insulin
      signaling in beta cell lines. We performed quantitative reverse-transcriptase
      polymerase chain reaction and immunohistochemistry on human pancreatic cancer and
      healthy pancreatic tissues (controls) to determine expression of adrenomedullin
      messenger RNA and protein, respectively. We studied the effects of adrenomedullin
      on insulin secretion by beta cell lines and whole islets from mice and on glucose
      tolerance in pancreatic xenografts in mice. We measured plasma levels of
      adrenomedullin in patients with pancreatic cancer, patients with type 2 diabetes
      mellitus, and individuals with normal fasting glucose levels (controls). RESULTS:
      Levels of adrenomedullin messenger RNA and protein were increased in human
      pancreatic cancer samples compared with controls. Adrenomedullin and conditioned
      media from pancreatic cell lines inhibited glucose-stimulated insulin secretion
      from beta cell lines and islets isolated from mice; the effects of conditioned
      media from pancreatic cancer cells were reduced by small hairpin RNA-mediated
      knockdown of adrenomedullin. Conversely, overexpression of adrenomedullin in mice
      with pancreatic cancer led to glucose intolerance. Mean plasma levels of
      adrenomedullin (femtomoles per liter) were higher in patients with pancreatic
      cancer compared with patients with diabetes or controls. Levels of adrenomedullin
      were higher in patients with pancreatic cancer who developed diabetes compared
      those who did not. CONCLUSIONS: Adrenomedullin is up-regulated in patients with
      pancreatic cancer and causes insulin resistance in beta cells and mice.

PMID- 22960656
TI  - Altered functions of plasmacytoid dendritic cells and reduced cytolytic activity
      of natural killer cells in patients with chronic HBV infection.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) modulates the immune system to escape
      clearance. Plasmacytoid dendritic cells (pDCs) initiate antiviral immunity and
      might determine outcomes of HBV infections. Functional defects in pDCs and
      natural killer (NK) cells have been reported in patients with chronic HBV
      infection. However, the mechanisms of these immune dysfunctions and the
      interactions between pDCs and NK cells have not been determined. We investigated
      features of pDCs from patients with chronic HBV infection and their interactions
      with NK cells. METHODS: We used flow cytometry and cytokine assays to analyze
      pDCs from patients with chronic HBV infection (118 aviremic and 67 viremic) and
      compared them with pDCs from uninfected individuals (controls). We performed
      coculture assays to analyze the ability of pDCs to activate heterologous NK
      cells. RESULTS: Circulating and hepatic pDCs from patients with chronic HBV
      infection had higher levels of activation than pDCs from controls and defective
      responses to stimulation with Toll-like receptor 9 ligand (TLR9-L), regardless of
      the patient's viral load. TLR9-L-activated pDCs from viremic patients with HBV
      did not induce cytolytic activity of NK cells. This altered function of pDCs was
      associated with reduced expression of OX40L and could be reproduced by incubating
      control pDCs with plasma from viremic patients with HBV. A high level of
      interferon-induced protein 10 (IP-10 or CXCL10) and hepatitis B surface and e
      antigens might induce these defective pDC functions. CONCLUSIONS: HBV escapes
      antiviral immunity by altering pDC functions, to disrupt interactions between pDC
      and NK cells. This could reduce immune control of HBV and lead to chronic
      infection.

PMID- 22960657
TI  - Segregation of a missense variant in enteric smooth muscle actin gamma-2 with
      autosomal dominant familial visceral myopathy.
AB  - BACKGROUND & AIMS: Familial visceral myopathy (FVM) is a rare inherited form of
      myopathic pseudo-obstruction; little is known about the genetic factors that
      cause this disorder. FVM is characterized by impaired functions of enteric smooth
      muscle cells, resulting in abnormal intestinal motility, severe abdominal pain,
      malnutrition, and even death. We searched for genetic factors that might cause
      this disorder. METHODS: We performed whole-exome sequence analysis of blood
      samples from 2 individuals in a family that had 7 members diagnosed with FVM.
      Sanger sequencing was used to analyze additional family members and 280
      individuals without this disorder (controls). Intestinal tissue samples from 4
      patients and 2 controls were analyzed by immunohistochemistry. Functional
      studies, including immunofluorescence, cell contractility, and actomyosin
      structure analyses, were performed using CRL-1976 and U2OS sarcoma cell lines.
      RESULTS: Whole-exome sequence analysis of DNA from 2 siblings identified 83 gene
      variants that were shared between the siblings and considered as possible disease
      causing changes. A heterozygous variant, R148S in enteric smooth muscle actin
      gamma-2 (ACTG2), segregated with disease phenotype. Intestinal smooth muscle
      (muscularis propria) from individuals with FVM had reduced levels of cytoplasmic
      ACTG2 and abnormal accumulation of the protein into intracellular inclusions
      compared with controls. Sarcoma cells that expressed exogenous ACTG2(R148S)
      incorporated reduced amounts of this protein into actin filaments compared with
      cells expressing ACTG2(wt) (P < .001). ACTG2(R148S) also interfered with actin
      cytoskeleton organization and the contractile activities of the cells, indicating
      a dominant-negative effect. These findings, along with the site of the variation
      in the protein, indicate that ACTG2 R148S interferes with actin filament
      assembly. CONCLUSIONS: We identified the R148S variant in ACTG2 as a cause of FVM
      in one family. The altered ACTG2 protein appears to aggregate, rather than form
      actin filaments, in intestinal smooth muscle tissue. This defect could impair
      contraction of the visceral smooth muscle cells and reduce bowel motility.

PMID- 22960658
TI  - Liver failure after extended hepatectomy in mice is mediated by a p21-dependent
      barrier to liver regeneration.
AB  - BACKGROUND & AIMS: Extended liver resection leads to hepatic failure because of a
      small remnant liver volume. Excessive parenchymal damage has been proposed as the
      principal cause of this failure, but little is known about the contribution of a
      primary deficiency in liver regeneration. We developed a mouse model to assess
      the regenerative capacity of a critically small liver remnant. METHODS: Extended
      (86%) hepatectomy (eHx) was modified to minimize collateral damage; effects were
      compared with those of standard (68%) partial hepatectomy (pHx) in mice. Markers
      of liver integrity and survival were evaluated after resection. Liver
      regeneration was assessed by weight gain, proliferative activity (analyses of
      Ki67, proliferating cell nuclear antigen, phosphorylated histone 3, mitosis, and
      ploidy), and regeneration-associated molecules. Knockout mice were used to study
      the role of p21. RESULTS: Compared with pHx, survival of mice was reduced after
      eHx, and associated with cholestasis and impaired liver function. However, no
      significant differences in hepatocyte death, sinusoidal injury, oxidative stress,
      or energy depletion were observed between mice after eHx or pHx. No defect in the
      initiation of hepatocyte proliferation was apparent. However, restoration of
      liver mass was delayed after eHx and associated with inadequate induction of
      Foxm1b and a p21-dependent delay in cell-cycle progression. In p21(-/-) mice, the
      cell cycle was restored, the gain in liver weight was accelerated, and survival
      improved after eHx. CONCLUSIONS: Significant parenchymal injury is not required
      for liver failure to develop after extended hepatectomy. Rather, liver
      dysfunction after eHx results from a transient, p21-dependent block before
      hepatocyte division. Therefore, a deficiency in cell-cycle progression causes
      liver failure after extended hepatectomy and can be overcome by inhibition of
      p21.

PMID- 22960659
TI  - Conditional disruption of Axin1 leads to development of liver tumors in mice.
AB  - BACKGROUND & AIMS: Mutations in components of the Wnt signaling pathway,
      including beta-catenin and AXIN1, are found in more than 50% of human
      hepatocellular carcinomas (HCCs). Disruption of Axin1 causes embryonic lethality
      in mice. We generated mice with conditional disruption of Axin1 to study its
      function specifically in adult liver. METHODS: Mice with a LoxP-flanked allele of
      Axin1 were generated by homologous recombination. Mice homozygous for the
      Axin1fl/fl allele were crossed with AhCre mice; in offspring, Axin1 was disrupted
      in liver following injection of beta-naphthoflavone (Axin1fl/fl/Cre mice). Liver
      tissues were collected and analyzed by quantitative real-time polymerase chain
      reaction and immunoprecipitation, histology, and immunoblot assays. RESULTS:
      Deletion of Axin1 from livers of adult mice resulted in an acute and persistent
      increase in hepatocyte cell volume, proliferation, and transcription of genes
      that induce the G(2)/M transition in the cell cycle and cytokinesis. A subset of
      Wnt target genes was activated, including Axin2, c-Myc, and cyclin D1. However,
      loss of Axin1 did not increase nuclear levels of beta-catenin or cause changes in
      liver zonation that have been associated with loss of the adenomatous polyposis
      coli (APC) or constitutive activation of beta-catenin. After 1 year, 5 of 9
      Axin1fl/fl/Cre mice developed liver tumors with histologic features of HCC.
      CONCLUSIONS: Hepatocytes from adult mice with conditional disruption of Axin1 in
      liver have a transcriptional profile that differs from that associated with loss
      of APC or constitutive activation of beta-catenin. It might be similar to a
      proliferation profile observed in a subset of human HCCs with mutations in AXIN1.
      Axin1fl/fl mice could be a useful model of AXIN1-associated tumorigenesis and
      HCC.

PMID- 22960661
TI  - Day-to-day variability of oscillatory impedance and spirometry in asthma and
      COPD.
AB  - Variability in airway function may be a marker of disease activity in COPD and
      asthma. The aim was to determine the effects of repeatability and airway
      obstruction on day-to-day variability in respiratory system resistance (Rrs) and
      reactance (Xrs) measured by forced oscillation technique (FOT). Three groups of
      10 subjects; normals, stable asthmatic and stable COPD subjects underwent daily
      FOT recordings for 7 days. Mean total and inspiratory Rrs and Xrs, and expiratory
      flow limitation (EFL) Index (inspiratory - expiratory Xrs), were calculated. The
      ICC's were high for all parameters in all groups. Repeatability, in terms of
      absolute units, correlated with airway obstruction and was therefore lowest in
      COPD. Day-to-day variability was due mostly to repeatability, with a small
      contribution from the mean value for some parameters. FOT measures are highly
      repeatable in health, stable asthma and COPD in relation to the wide range of
      measures between subjects. For home monitoring in asthma and COPD, either the
      coefficient of variation or individualized SDs could be used to define day-to-day
      variability.

PMID- 22960662
TI  - PharmGKB summary:  zidovudine pathway.

PMID- 22960663
TI  - A species-specific view of song representation in a sensorimotor nucleus.
AB  - Songbirds constitute a powerful model system for the investigation of how complex
      vocal communication sounds are represented and generated, offering a neural
      system in which the brain areas involved in auditory, motor and auditory-motor
      integration are well known. One brain area of considerable interest is the
      nucleus HVC. Neurons in the HVC respond vigorously to the presentation of the
      bird's own song and display song-related motor activity. In the present paper, we
      present a synthesis of neurophysiological studies performed in the HVC of one
      songbird species, the canary (Serinus canaria). These studies, by taking
      advantage of the singing behavior and song characteristics of the canary, have
      examined the neuronal representation of the bird's own song in the HVC. They
      suggest that breeding cues influence the degree of auditory selectivity of HVC
      neurons for the bird's own song over its time-reversed version, without affecting
      the contribution of spike timing to the information carried by these two song
      stimuli. Also, while HVC neurons are collectively more responsive to forward
      playback of the bird's own song than to its temporally or spectrally modified
      versions, some are more broadly tuned, with an auditory responsiveness that
      extends beyond the bird's own song. Lastly, because the HVC is also involved in
      song production, we discuss the peripheral control of song production, and
      suggest that interspecific variations in song production mechanisms could be
      exploited to improve our understanding of the functional role of the HVC in
      respiratory-vocal coordination.

PMID- 22960664
TI  - Current state-of-the-art of auditory functional MRI (fMRI) on zebra finches:
      technique and scientific achievements.
AB  - Songbirds provide an excellent model system exhibiting vocal learning associated
      with an extreme brain plasticity linked to quantifiable behavioral changes. This
      animal model has thus far been intensively studied using electrophysiological,
      histological and molecular mapping techniques. However, these approaches do not
      provide a global view of the brain and/or do not allow repeated measures, which
      are necessary to establish correlations between alterations in neural substrate
      and behavior. In contrast, functional Magnetic Resonance Imaging (fMRI) is a non
      invasive in vivo technique which allows one (i) to study brain function in the
      same subject over time, and (ii) to address the entire brain at once. During the
      last decades, fMRI has become one of the most popular neuroimaging techniques in
      cognitive neuroscience for the study of brain activity during various tasks
      ranging from simple sensory-motor to highly cognitive tasks. By alternating
      various stimulation periods with resting periods during scanning, resting and
      task-specific regional brain activity can be determined with this technique.
      Despite its obvious benefits, fMRI has, until now, only been sparsely used to
      study cognition in non-human species such as songbirds. The Bio-Imaging Lab
      (University of Antwerp, Belgium) was the first to implement Blood Oxygen Level
      Dependent (BOLD) fMRI in songbirds - and in particular zebra finches - for the
      visualization of sound perception and processing in auditory and song control
      brain regions. The present article provides an overview of the establishment and
      optimization of this technique in our laboratory and of the resulting scientific
      findings. The introduction of fMRI in songbirds has opened new research avenues
      that permit experimental analysis of complex sensorimotor and cognitive processes
      underlying vocal communication in this animal model.

PMID- 22960665
TI  - Facile formation and redox of benzoxazole-2-thiolate-bridged dinuclear Pt(II/III)
      complexes.
AB  - Reaction of [Pt(L)(MU-Cl)](2) (L = ppy (2-phenylpyridine) or bzq
      (benzo[h]quinoline)) with 2-mercaptobenzoxazole (NOSH) and NaOAc in THF at r.t.
      yields the dinuclear Pt(II) d(8)-d(8) complexes [Pt(2)L(2)(MU-NOS-kappaN,S)(2)]
      (L = ppy, 1; L = bzq, 2) and the Pt(III) d(7)-d(7) complexes [Pt(2)(ppy)(2)(MU
      NOS-kappaN,S)(2)(NOS-kappaS)(2)] (L = ppy, 3; L = bzq, 4) in one pot. The C,N
      cyclometalated ligand is chelating whereas the N,S-donating benzoxazole-2
      thiolates doubly bridge the two metal centers. The Pt...Pt separations of
      3.0204(3) and 2.9726(8) A in 1 and 2 contract to 2.685(1) A in 3 and 2.6923(3) A
      in 4, respectively, when two S-bound thiolate ligands coordinate trans- to the
      Pt...Pt axis. However, cyclometalation is preserved and there is minimum
      perturbation of the bridging ligands. Complexes 3 and 4 can be also obtained by
      oxidative addition of the thiolate ligand. In the presence of NaBH(4), 3 and 4
      can be reduced to 1 and 2, respectively. At r.t., 1 and 2 exhibit intense orange
      red luminescence at 625 nm and 631 nm, respectively. The electrochemical
      properties of 1-4 have been also discussed.

PMID- 22960666
TI  - Cerium dioxide nanoparticles can interfere with the associated cellular
      mechanistic response to diesel exhaust exposure.
AB  - The aim of this study was to compare the biological response of a sophisticated
      in vitro 3D co-culture model of the epithelial airway barrier to a co-exposure of
      CeO(2) NPs and diesel exhaust using a realistic air-liquid exposure system.
      Independent of the individual effects of either diesel exhaust or CeO(2) NPs
      investigation observed that a combined exposure of CeO(2) NPs and diesel exhaust
      did not cause a significant cytotoxic effect or alter cellular morphology after
      exposure to diesel exhaust for 2h at 20MUg/ml (low dose) or for 6h at 60MUg/ml
      (high dose), and a subsequent 6h exposure to an aerosolized solution of CeO(2)
      NPs at the same doses. A significant loss in the reduced intracellular
      glutathione level was recorded, although a significant increase in the oxidative
      marker HMOX-1 was found after exposure to a low and high dose respectively. Both
      the gene expression and protein release of tumour necrosis factor-alpha were
      significantly elevated after a high dose exposure only. In conclusion, CeO(2)
      NPs, in combination with diesel exhaust, can significantly interfere with the
      cell machinery, indicating a specific, potentially adverse role of CeO(2) NPs in
      regards to the biological response of diesel exhaust exposure.

PMID- 22960667
TI  - A method to identify RNA A-to-I editing targets using I-specific cleavage and
      exon array analysis.
AB  - RNA A-to-I editing is the most common single-base editing in the animal kingdom.
      Dysregulations of RNA A-to-I editing are associated with developmental defects in
      mouse and human diseases. Mouse knockout models deficient in ADAR activities show
      lethal phenotypes associated with defects in nervous system, failure of
      hematopoiesis and reduced tolerance to stress. While several methods of
      identifying RNA A-to-I editing sites are currently available, most of the
      critical editing targets responsible for the important biological functions of
      ADARs remain unknown. Here we report a method to systematically analyze RNA A-to
      I editing targets by combining I-specific cleavage and exon array analysis. Our
      results show that I-specific cleavage on editing sites causes more than twofold
      signal reductions in edited exons of known targets such as Gria2, Htr2c, Gabra3
      and Cyfip2 in mice. This method provides an experimental approach for genome-wide
      analysis of RNA A-to-I editing targets with exon-level resolution. We believe
      this method will help expedite inquiry into the roles of RNA A-to-I editing in
      various biological processes and diseases.

PMID- 22960668
TI  - A comparison of convex and non-convex compressed sensing applied to
      multidimensional NMR.
AB  - The resolution of multidimensional NMR spectra can be severely limited when
      regular sampling based on the Nyquist-Shannon theorem is used. The theorem binds
      the sampling rate with a bandwidth of a sampled signal and thus implicitly
      creates a dependence between the line width and the time of experiment, often
      making the latter one very long. Recently, Candes et al. (2006) [25] formulated a
      non-linear sampling theorem that determines the required number of sampling
      points to be dependent mostly on the number of peaks in a spectrum and only
      slightly on the number of spectral points. The result was pivotal for rapid
      development and broad use of signal processing method called compressed sensing.
      In our previous work, we have introduced compressed sensing to multidimensional
      NMR and have shown examples of reconstruction of two-dimensional spectra. In the
      present paper we discuss in detail the accuracy and robustness of two compressed
      sensing algorithms: convex (iterative soft thresholding) and non-convex
      (iteratively re-weighted least squares with local l(0)-norm) in application to
      two- and three-dimensional datasets. We show that the latter method is in many
      terms more effective, which is in line with recent works on the theory of
      compressed sensing. We also present the comparison of both approaches with
      multidimensional decomposition which is one of the established methods for
      processing of non-linearly sampled data.

PMID- 22960669
TI  - Sensitivity enhancement of double quantum NMR spectroscopy by modified CPMG.
AB  - A modified Carr-Purcell-Meiboom-Gill (CPMG) sequence for sensitivity enhancement
      of dipolar coupled homonuclear spin pairs in static solid-state NMR is presented.
      The modified CPMG block uses the Hahn-solid-Hahn echo as basic element of the
      CPMG echo train to refocus the homonuclear dipolar coupling and chemical shift
      anisotropy. The new CPMG sequence is dubbed as Hahn-solid-Hahn Carr-Purcell
      Meiboom-Gill (HSHCPMG). We demonstrate a gain in signal to noise ratio of
      approximately 4.2 using HSHCPMG sequence in double quantum filtered CP experiment
      for 5%-(13)C(2)-(15)N-glycine. The resulting gain in sensitivity in the spikelet
      spectrum does not compromise the anisotropic information that is available from
      static NMR lineshapes. As an example, relative orientation angles of chemical
      shift anisotropy tensors for the alpha and carbonyl carbons in glycine are
      determined from the 2D DOQSY experiment recorded with the HSHCPMG block in the
      acquisition dimension. The resultant relative orientation angles of the two CSA
      tensors are compared to those obtained from 2D DOQSY experiment acquired without
      sensitivity enhancement as well as to the data as available from single crystal
      NMR experiments.

PMID- 22960670
TI  - Dynamic evolution for liquid-state nuclear spins and Berry phase of mixed state
      in a magnetic resonance.
AB  - Dynamic evolution for liquid-state nuclear spin in a magnetic resonance is
      investigated based on Bloch sphere structure under the time-dependent modified
      Bloch equation. We show that the magnetization is related to the magnetic field
      strength but approximately independent of the initial unpolarized spin state
      after a very short evolving time. We predict that the Berry phase transition of
      the nuclear spin system take place in a quasicyclic evolution for some initial
      states, resulting in that the evolving memory of nuclear spin polarization is
      kept in terms of the Berry phase. The findings provide another clue to search for
      quantum memory devices in such a system on the basis of the geometric phase.

PMID- 22960671
TI  - Inter-tester reliability of discriminatory examination items for sub-classifying
      non-specific low back pain.
AB  - OBJECTIVE: To investigate the inter-tester reliability of a non-specific low back
      pain examination procedure, for sub-classifying non-specific low back pain.
      DESIGN: Reliability study. PARTICIPANTS: Thirty patients with non-specific low
      back pain (12 males, 18 females, mean age: 27.7 years (standard deviation 10.3)
      and 7 physiotherapists (raters). METHODS: Based on a health professionals'
      consensus via focus groups and a Delphi servey, an examination procedure was
      developed comprising 206 items discriminatory for non-specific low back pain, 108
      of which were from the History (clinical questions) and 98 from the Physical
      Examination (clinical tests) section. Utilizing this procedure, each patient was
      examined by a blinded pair of raters. RESULTS: Moderate to excellent agreement
      was obtained in 125 (61%) items (77 History and 48 Physical Examination items),
      47 of which obtained substantial or excellent agreement (kappa >0.61), 37
      moderate agreement (kappa between 0.41 and 0.6), and 41 excellent percentage
      agreements. Poor reliability (kappa < 0.41) was yielded in the remaining 81 items
      (31 History and 50 Physical Examination items). CONCLUSION: Satisfactory
      reliability was obtained in nearly two-thirds of History and half of the Physical
      Examination items on a non-specific low back pain assessment list generated
      through consensus agreement. These findings provide clinicians and researchers
      with valuable information regarding which items are considered reliable and can
      be utilized in non-specific low back pain patient evaluation/assessment
      procedures, classification attempts and clinical trials.

PMID- 22960672
TI  - Who drives the ciliary highway?
AB  - Cilia are protrusions on the surface of cells. They are frequently motile and
      function to propel cells in an aqueous environment or to generate fluid flow.
      Equally important is the role of immotile cilia in detecting environmental
      changes or in sensing extracellular signals. The structure of cilia is supported
      by microtubules, and their formation requires microtubule-dependent motors,
      kinesins, which are thought to transport both structural and signaling ciliary
      proteins from the cell body into the distal portion of the ciliary shaft. In
      multicellular organisms, multiple kinesins are known to drive ciliary transport,
      and frequently cilia of a single cell type require more than one kinesin for
      their formation and function. In addition to kinesin-2 family motors, which
      function in cilia of all species investigated so far, kinesins from other
      families contribute to the transport of signaling proteins in a tissue-specific
      manner. It is becoming increasingly obvious that functional relationships between
      ciliary kinesins are complex, and a good understanding of these relationships is
      essential to comprehend the basis of biological processes as diverse as
      olfaction, vision, and embryonic development. 

PMID- 22960674
TI  - Features of Urrets-Zavalia syndrome after descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To report a case series of pupil abnormalities consistent with features
      of Urrets-Zavalia syndrome (UZS) after Descemet stripping automated endothelial
      keratoplasty (DSAEK) for corneal edema secondary to corneal endothelial cell
      dysfunction. METHODS: Retrospective chart analysis of subjects who developed UZS
      after DSAEK at the University of Texas Southwestern Medical Center. RESULTS: We
      present a series of 7 eyes with features consistent with UZS, after undergoing
      DSAEK. Elevated intraocular pressures (IOP) were noted in the early postoperative
      period in all cases. Five of 7 had graft dislocation in the postoperative period
      and required rebubbling or repeat DSAEK to obtain a well-apposed graft. Patients
      were followed for 3 to 14 months and showed improvement in visual acuity and IOP,
      but fixed dilated pupils persisted. CONCLUSION: A fixed irregular or dilated
      pupil is a rare complication that can be associated with DSAEK surgery. Patients
      with an elevated IOP and complicated postoperative course seem to be at greater
      risk for developing iris ischemia and pupil abnormalities consistent with the
      diagnosis of UZS.

PMID- 22960673
TI  - Self-expandable metallic stents in patients with stage IV obstructing colorectal
      cancer.
AB  - BACKGROUND: The aim of the present study was to analyze the results of our
      experience with elective placement of self-expandable metallic stents (SEMS) in
      patients with stage IV obstructing colorectal cancer. A systematic review of the
      literature was also carried out to analyze the factors influencing the results of
      SEMS placement and to determine if there has been any improvement in the more
      recent period. MATERIALS AND METHODS: The results of a personal series of 100
      patients were analyzed. There was no case of mortality or major morbidity. The
      systematic review included 27 articles published from April 2007 to December
      2011. RESULTS: In our experience the technical success rate was 96% and the
      clinical success rate was 92%. During the follow-up period a repeat colonoscopy
      was needed in 31% of the patients for recurrent symptoms of obstruction due to
      fecal impaction (19%), tumor growth (8%), or stent dislodgment (4%). Review of
      the literature showed similar results, with a significant improvement in the
      reports of the last 6 years; procedures performed on an emergency basis had
      poorer results. CONCLUSIONS: Self-expandable metallic stent placement offers a
      valid alternative to surgery in patients with obstructing stage IV colorectal
      cancer, but careful follow-up is required.

PMID- 22960689
TI  - Real-time PCR and pyrosequencing for differentiation of medically relevant
      Bartonella species.
AB  - Multiple Bartonella species cause disease in humans. Although fast and accurate
      species differentiation could inform effective treatment interventions, species
      level diagnosis of Bartonella infections is not typical. Here we describe a real
      time PCR and pyrosequencing based algorithm for rapid differentiation of at least
      11 medically relevant Bartonella spp.

PMID- 22960690
TI  - Performance of two commercial rapid methods for sampling and detection of
      Listeria in small-scale cheese producing and salmon processing environments.
AB  - Two commercially available all-in-one swab rapid detection systems for Listeria
      spp. (InSite Listeria Test and Path-Chek hygiene Listeria) were tested for
      performance in cheese production environments and salmon processing facilities.
      Sampling was conducted both on clean surfaces and during production. A total of
      338 samples were taken using the swabs (175 in cheese environments, 163 in salmon
      environments). Conventional sampling using sterile cloths and standardized
      qualitative detection of Listeria spp. according to NMKL method no. 136 was
      performed in parallel from 64 sampling sites in the salmon processing facilities
      and 40 sampling sites in the cheese production facilities. Results showed that
      both rapid swab tests detected Listeria spp.; however, they returned significant
      amounts of false positives. Presence of Listeria spp. was indicated in 47% and
      41% of all swabs in the cheese and salmon environments, respectively. Enrichment
      followed by selective plating and Listeria specific PCR confirmed none of the 82
      presumptive positive swabs from the cheese environment and 16 of 67 presumptive
      positive swabs from the salmon environments, respectively. Further analysis
      showed that several other bacteria, including Enterococcus spp. and
      Carnobacterium maltaromaticum, were the source of false positive swab results.
      From salmon processing facilities, using cloth sampling and standard analyses,
      22% Listeria positive sampling sites were confirmed compared to 9% and 11%
      positives obtained using InSite or Path-Chek detection systems. From the cheese
      production environments, no Listeria positive sites were confirmed using either
      swab or cloth sampling. In conclusion, the use of these rapid detection methods
      was not suited in the selected environments due to large numbers of false
      positives, caused by the background flora.

PMID- 22960691
TI  - Controlled release of dry reagents in porous media for tunable temporal and
      spatial distribution upon rehydration.
AB  - Novel methods are demonstrated that enable controlled spatial and temporal
      rehydration of dried reagents in a porous matrix. These methods can be used in
      paper-based microfluidic assays to define reagent concentrations over time at
      zones downstream for improved performance, and can reduce costs by simplifying
      the manufacturing process with the use of a single porous substrate. First, the
      creation of uniform reagent pulses from patterned arrays of dried reagent is
      demonstrated. Second, reagents are stored dry in separate regions of the porous
      matrix so that they can be combined upon rehydration for immediate use in the
      device. Third, reagents are reconstituted sequentially from dry storage depots
      with tunable delivery times. Fourth, the total time for dissolution is varied to
      achieve a range of reagent delivery times to a downstream region. Finally, the
      utility of these control methods is demonstrated in the context of real-time
      reagent rehydration and mixing on a porous device.

PMID- 22960692
TI  - Anti-inflammatory effects of insulin regular and flunixin meglumine on
      endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an
      ovine model.
AB  - BACKGROUND: Endotoxemia is a major cause of mortality in large animals and there
      are several therapeutic regimens for the treatment of endotoxemia. Recent studies
      have suggested the anti-inflammatory effects of insulin in endotoxemic human and
      laboratory animal models but to the best of our knowledge there is no report on
      the possible therapeutic effect of insulin in large animal endotoxemia.
      OBJECTIVE: This experiment was conducted to evaluate the anti-inflammatory
      effects of insulin regular compared with flunixin meglumine on the treatment of
      endotoxemia in sheep. METHODS: Lipopolysaccharide from Escherichia coli was
      administered intravenously to ewes. Anti-inflammatory effects of flunixin
      meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated
      by determination of serum concentrations of acute phase proteins, inflammatory
      cytokines and oxidative stress biomarkers. RESULTS: Insulin regular at 3 IU/kg
      controlled the acute phase response following endotoxemia induction. The anti
      inflammatory potency of insulin regular at 3 IU/kg was significantly higher than
      at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05). CONCLUSION:
      Insulin regular induces its anti-inflammatory effects in a dose-dependent manner.
      Intravenous use of insulin regular can be a potential new therapeutic regimen for
      endotoxemia in large animal medicine.

PMID- 22960693
TI  - The impact of carbon-hydrogen bond dissociation energies on the prediction of the
      cytochrome P450 mediated major metabolic site of drug-like compounds.
AB  - Cytochrome P450 is a family of enzymes which is estimated to be responsible for
      over 75% of phase I drug metabolism. In this process carbon hydrogen bonds (C-H)
      are broken for hydroxylation indicating that the bond dissociation energy (BDE)
      plays a pivotal role. A host of experimentally derived C-H BDEs were benchmarked
      against their theoretical counterparts and an excellent correlation was found
      (R(2) = 0.9746, n = 100). The C-H BDEs were calculated for fifty drugs with known
      major hydrogen abstraction sites. Of those twelve (24%) had their major metabolic
      site at the lowest C-H BDE. The most prominent factor in determining the
      metabolic site is the presence of tertiary and secondary amine moieties (44%).
      Other features such as lipophilicity and steric accessibility of the pertinent
      molecular scaffolds are also important. Nevertheless, out of the 586 C-H BDEs
      calculated the average of the major hydrogen abstraction sites are statistically
      significantly lower by 6.9-12.8 kcal/mol (p-value = 7.257 * 10(-9)). This means
      that C-H BDEs are an indispensable component in building reliable models of first
      pass metabolism of xenobiotics.

PMID- 22960694
TI  - 2,6-Disubstituted imidazo[2,1-b][1,3,4]thiadiazoles: search for anticancer
      agents.
AB  - In this study, some novel 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles 4
      (a-i), 7 (a-p) and 11 (a-i) were synthesized from 5-substituted-1,3,4-thiadiazol
      2-amine. The newly synthesized compounds 4a, 4b, 4c, 4e, 4g, 7j, 7l, 11b and 11c
      were evaluated in the National Cancer Institute for single dose in vitro primary
      cytotoxicity assay. Among the tested nine compounds, compound 4b (107166/760239)
      and 4c (107168/760240) were passed the criteria for activity in this assay and
      scheduled automatically for evaluation against the full panel of 60 human tumor
      cell lines at a minimum of five concentrations at 10-fold dilutions. 3-(2-(4
      methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)aniline (4c) exhibited
      significant in vitro anticancer activity against Non Small Cell Lung Cancer HOP
      92 cell line (GI(50): 0.114 MUM) and Renal Cancer CAKI-1 cell line (GI(50): 0.743
      MUM).

PMID- 22960696
TI  - D-proline-based peptidomimetic inhibitors of anthrax lethal factor.
AB  - In this work we reported the generation of d-proline-derived hydroxamic acids as
      inhibitors of anthrax lethal factor (LF), taking advantage of a pyrrolidine ring
      as the central scaffold and a hydroxamate group as the Zn(2+) chelating agent.
      The introduction of two hydrophobic groups addressing the S1' subsite and a long
      substrate-binding groove was conceived by overlapping the bioactive conformations
      of two reported LF inhibitors. Micromolar affinity of compound 38 suggested cis-3
      substituted-1-sulfonamido-d-proline hydroxamic acids as a promising class of
      peptidomimetic inhibitors for developing novel LF inhibitors.

PMID- 22960695
TI  - Ligand-based designing, in silico screening, and biological evaluation of new
      potent fructose-1,6-bisphosphatase (FBPase) inhibitors.
AB  - Fructose-1,6-bisphosphatase - hereafter abbreviated as FBPase has been recently
      implicated in diabetes prompting several attempts to discover and optimize new
      FBPase inhibitors. Toward this end we explored the pharmacophoric space of 136
      FBPase inhibitors using three diverse sets of inhibitors. This identified 520
      pharmacophores that were subsequently clustered into 104 groups. Cluster centers
      were evaluated by receiver operating characteristic (ROC) curves analysis and
      correlation with bioactivities of collected compounds. Pharmacophore model
      Hypo1/7 illustrated the best combination of classification power (ROC-AUC) and
      correlation with bioactivity. Two other pharmacophores (Hypo2/1 and Hypo2/6) were
      found to be mergeable and their combined model (Hypo2-1/2-6) illustrated
      excellent ROC performance. We employed Hypo1/7 and Hypo2-1/2-6 models to screen
      the National Cancer Institute (NCI) list of compounds. In silico mining
      identified 18 FBPase inhibitors out of which six were of sub-micromolar IC(50)
      values.

PMID- 22960697
TI  - Synthesis and in vitro antimycobacterial and isocitrate lyase inhibition
      properties of novel 2-methoxy-2'-hydroxybenzanilides, their thioxo analogues and
      benzoxazoles.
AB  - A new series of 2-methoxy-2'-hydroxybenzanilide derivatives and their thioxo
      analogues have been synthesised and characterised by IR, NMR and elemental
      analysis. These compounds were investigated for their in vitro antimycobacterial
      activities against Mycobacterium tuberculosis 331/88, Mycobacterium avium 330/88,
      Mycobacterium kansasii 235/80, clinically isolated M. kansasii 6509/96 and the
      ability to act as in vitro isocitrate lyase inhibitors. The best ICL inhibitors
      were two compounds from the thiobenzanilide group (8f, 8m), which exhibited an
      inhibition potential that was equal to the standard compound, 3-nitropropionic
      acid. In addition, the best antimycobacterial properties were exhibited by
      benzanilide derivatives 6h, 6k and 6l with 5-Cl and 4' or 5' Cl/Br substitution.
      For all the thiobenzanilide derivatives tested, two conformers were observed in
      the NMR spectra, which is most likely due to the hindered rotation of the C-N
      bond.

PMID- 22960698
TI  - Benzofuranones as potential antinociceptive agents: structure-activity
      relationships.
AB  - This work evaluates the antinociceptive properties of benzofuranones using
      chemically induced models of pain and the hot plate test. All the compounds
      exhibited significant antinociceptive activity, with 3-[2-(4-chlorophenyl)-2
      oxoetil]-2-benzofuran-1(3H)-one (3d) being the most active. According to the
      application of the Topliss method, the 2pi-pi(2) parameter was the preponderant
      one, indicating that the hydrophobicity (pi) seems to be more involved in the
      antinociceptive activity. Based on the table of other possible substituents
      proposed by Topliss, three derived from compound 3d were tested. 3-[2-(3
      methoxyphenyl)-2-oxoetil]-2-benzofuran-1(3H)-one (3g) showed greater
      antinociceptive activity with better pharmacokinetic properties predicted. These
      results show the efficiency of the Topliss Method as a research tool for the
      discovery of potential candidate molecules for a new antinociceptive drug.

PMID- 22960699
TI  - Development of emergency department load relief area--gauging benefits in
      empirical terms.
AB  - INTRODUCTION: The primary goal of this investigation was to develop a simulation
      model to evaluate the various internal and external factors affecting patient
      flow and crowding in the emergency department (ED). In addition, a few
      recommendations are proposed to reconfigure the patient flow to improve ED
      capacity while maintaining service quality. METHODS: In this research, we present
      a simulation study conducted in the ED at the "S Hospital" located in Seoul.
      Based on patient flow data and process analysis, a simulation model of patient
      throughput in the ED has been developed. We evaluated simulations of diverting
      the specific patient load in the light of our proposed recommendations to a
      separately managed area named as the ED load relief area (ED-LRA) and analyzing
      potential effects on overall length of stay (LOS) and waiting time (WT). RESULTS:
      What-if analyses have been proposed to identify key issues and investigate the
      improvements as per our proposed recommendations. The simulation results suggest
      that specific patient load diversion is needed to ensure desired outcomes. With
      the diversion of specific patient load to ED-LRA, there is a reduction of 40.60%
      in mean LOS and 42.5% in WT with improved resource utilization. As a result,
      opening of an ED-LRA is justified. CONCLUSIONS: Real-world systems are often too
      intricate for analytical models and often too expensive to trial with directly.
      Simulation models allow the modeling of this intricacy and enable experimentation
      to make inferences about how the actual system might perform. Our simulation
      study modeled that diverting the specific patient load to ED-LRA produced an
      improvement in overall ED's LOS and WT.

PMID- 22960700
TI  - Cardiac arrest in an obstetric patient: a simulated emergency.

PMID- 22960701
TI  - Evaluation of simulation-based training model on vascular anastomotic skills for
      surgical residents.
AB  - INTRODUCTION: Reduced work hours and concerns over patient safety have encouraged
      surgical educators to find methods to advance resident skills more efficiently.
      Simulation provides the opportunity to improve technical surgical skills outside
      the operating room. We hypothesized that practice on surgical task simulators
      would improve residents' technical performance of vascular anastomotic technique.
      METHODS: Senior general surgery residents at an academic medical center completed
      pretests and posttests on 3 vascular surgery simulators: femoral-popliteal
      bypass, carotid endarterectomy, and abdominal aortic aneurysm repair. The initial
      training sessions began with a 15-minute instructional video on how to perform
      the procedures, followed by supervised sessions in anastomotic technique with
      attending vascular surgeons. Initial individual sessions were videotaped as a
      pretest, and the final attempt was videotaped as the posttest. Each test was
      evaluated by a single experienced attending vascular surgeon blinded to the
      examinees. Anastomoses were graded using a performance rating and a modified
      objective structured assessment of technical skill rating. Results were analyzed
      using mixed model P values. RESULTS: The residents showed statistically
      significant improvement between the pretest and the posttest in both their
      performance rating (1.9 vs. 2.4, P = 0.02) and the objective structured
      assessment of technical skill (2.6 vs. 3.1, P = 0.01), as well as in most subsets
      of each assessment scale. CONCLUSIONS: We conclude that practice using simulated
      anastomotic models leads to measurable improvement in vascular anastomotic
      technique in senior general surgery residents.

PMID- 22960702
TI  - To die or not to die? A review of simulated death.
AB  - SUMMARY STATEMENT: Simulation as an educational technique is increasingly used in
      health care to teach about managing critical events and life-threatening
      situations and, infrequently, to teach about death. There is considerable
      controversy over whether to allow the simulator to die during a session when
      death is not a predefined learning objective. Some educators never allow the
      simulator to die unless death is the objective of the scenario, and others allow
      the simulator to die unexpectedly during any scenario. We do not know whether
      such a fatal event may affect a student's learning process and emotions, and no
      randomized trials have been conducted to determine the impact of simulated death.
      In this narrative review, we survey the literature on simulated death during
      health care training, present arguments for and against the broad incorporation
      of such training in curricula for health care providers, and outline
      recommendations for using death scenarios in health care simulation.

PMID- 22960703
TI  - Haemophilia registry of the Medical Committee of the Swiss Hemophilia Society.
      Update and annual survey 2010-2011.
AB  - The Haemophilia Registry of the Swiss Haemophilia Society was created in the year
      2000. The latest records from October 31st 2011 are presented here. Included are
      all patients with haemophilia A or B and other inherited coagulation disorders
      (including VWD patients with R-Co activity below 10%) known and followed by the
      11 paediatric and 12 adult haemophilia treatment or reference centers. Currently
      there are 950 patients registered, the majority of which (585) having haemophilia
      A. Disease severity is graded according to ISTH criteria and its distribution
      between mild, moderate and severe haemophilia is similar to data from other
      European and American registries. The majority (about two thirds) of Swiss
      patients with haemophilia A or B are treated on-demand, with only about 20% of
      patients being on prophylaxis. The figure is different in paediatrics and young
      adults (1st and 2nd decades), where 80 to 90% of patients with haemophilia A are
      under regular prophylaxis. Interestingly enough, use of factor concentrates,
      although readily available, is rather low in Switzerland, especially when taking
      the country's GDP into account: The total amount of factor VIII and IX was 4.94 U
      pro capita, comparable to other European countries with distinctly lower incomes
      (Poland, Slovakia, Hungary). This finding is mainly due to the afore mentioned
      low rate of prophylactic treatment of haemophilia in our country. Our registry
      remains an important instrument of quality control of haemophilia therapy in
      Switzerland.

PMID- 22960704
TI  - Effects of fluorine-containing opener of ATP-sensitive potassium channels,
      pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium
      channels.
AB  - Fluorine-containing pinacidil-derivative flocalin is an effective adenosine
      triphosphate-sensitive potassium (K(ATP))-channel opener with pronounced
      vasodilatory, cardioprotective effects and low general toxicity. By activating
      cardiac K(ATP) channels, flocalin hyperpolarizes cardiac myocytes, decreases
      their excitability, reduces Ca(2+) entry, and inhibits Ca(2+)-dependent
      signalling processes. Since our previous studies indicated that the drug also
      influences the rate of rise and amplitude of the cardiomyocyte's action
      potential, here we have investigated its possible actions on depolarizing inward
      currents through voltage-gated sodium (VGSC) and L-type calcium (VGCC) channels.
      Experiments were conducted on cultured cardiac myocytes prepared from the whole
      hearts of neonatal rats and maintained in culture for 1-3 days using whole-cell
      patch-clamp technique with no distinction of myocyte's type. Flocalin
      concentration dependently inhibited the Na(+) inward current through VGSCs with
      IC(50) = 17.4 MUM and a maximal extent of 0.54, slowed down its inactivation
      kinetics, and hyperpolarized steady-state inactivation by 5.6 mV. The drug also
      inhibited calcium current through L-type VGCCs with IC(50) = 24.1 MUM and a
      maximal block of 0.38, without affecting its inactivation but producing 5.3-mV
      hyperpolarization shifting of steady-state activation. Inhibition of both
      depolarizing currents by flocalin in addition to its ability to open K(ATP)
      channels enhances the suppressive action of the drug on cardiac excitability and
      broadens its pharmacological effects. Since, according to our previous data,
      cardiac K(ATP)-channel opening by flocalin occurs with EC(50) = 8 MUM, the
      possibility of partial blockade of VGSC and L-type VGCCs should be considered
      when determining the therapeutic concentrations of the compound during its use as
      a cardioprotector.

PMID- 22960705
TI  - Structural biology of the PCI-protein fold.
AB  - The PCI fold is based on a stack of alpha-helices topped with a winged-helix
      domain and is found in a range of proteins that form central parts of large
      complexes such as the proteasome lid, the COP9 signalosome, elongation factor
      eIF3, and the TREX-2 complex. Recent structural determinations have given
      intriguing insight into how these folds function both to facilitate the
      generation of larger proteinaceous assembles and also to interact functionally
      with nucleic acids. 

PMID- 22960706
TI  - T-2 toxin induced skin inflammation and cutaneous injury in mice.
AB  - T-2 toxin is one of the most toxic among several trichothecenes involved in both
      human and animal poisoning cases. We investigated the biochemical and
      histological alterations behind inflammation and cutaneous injury caused by T-2
      toxin. Swiss albino mice were exposed to T-2 toxin topically at doses of 0.5, 1
      and 2 LD50 (2.97, 5.94 and 11.88 mg/kg respectively) and observed till 3, 24 and
      72 h. Topical application of T-2 toxin resulted in skin oxidative stress in terms
      of increased reactive oxygen species generation, lipid peroxidation and
      neutrophil mediated myeloperoxidase activity. The histological alterations
      include degenerative changes like vacuolation, ballooning of basal keratinocytes
      and infiltration of inflammatory cells in dermis. The mRNA levels of skin pro
      inflammatory cytokines TNF-alpha, IL-6, and IL-1beta showed significant up
      regulation. Anti-inflammatory cytokines IL-10 showed significant up regulation at
      24h whereas IL-4 showed down regulation for all the doses and time points.
      Gelatin zymography and immunoblot analysis of matrix metalloproteinases (MMP)-9
      and 2 indicated MMP activation and their role in degenerative skin histological
      changes. Time dependent increase in inducible nitric oxide synthase levels was
      seen. Immunoblot analysis revealed significant increase in the levels of
      phosphorylated p38 mitogen activated protein kinase (MAPK). Flow cytometry
      analysis of propidium iodide stained epidermal cells showed increase in sub-G1
      population at all the doses and time points indicating apoptosis. In summary, T-2
      toxin induced skin inflammation and cutaneous injury is mediated through
      oxidative stress, activation of myeloperoxidase, MMP activity, increase in
      inflammatory cytokines, activation of p38 MAPK and apoptosis of epidermal cells
      leading to degenerative skin histological changes.

PMID- 22960707
TI  - Spironolactone release from liquisolid formulations prepared with CapryolTM 90,
      Solutol(r) HS-15 and Kollicoat(r) SR 30 D as non-volatile liquid vehicles.
AB  - The purpose of the study is to enhance dissolution of spironolactone as a model
      hydrophobic drug through application of liquisolid technology. Spironolactone is
      prepared as liquisolid formulations, and its dissolution property is evaluated
      and compared to that of conventional spironolactone tablets and pure
      spironolactone. Three non-volatile liquid vehicles were used in the design of
      spironolactone liquisolid formulations, CapryolTM 90, Synperonic(r) PE/L61 in
      combination with Solutol(r) HS-15 at a ratio of 1:1, and Kollicoat(r) SR 30 D.
      Spironolactone liquisolid formulations were tested according to British
      Pharmacopoeia (BP) quality control tests. Furthermore, the prepared liquisolid
      powder formulations were evaluated via differential scanning calorimetry (DSC),
      Fourier transform infrared (FT-IR) and scanning electron microscopy. Also,
      liquisolid formulations were subjected to testing of storage stability at high
      relative humidity. The results indicated that most of liquisolid tablets met the
      BP requirements. Dissolution results indicate that release of spironolactone was
      significantly increased (P<0.05) through liquisolid formulations, compared to
      pure drug. Liquisolid powder formulations formulated from a combination of
      Synperonic(r) PE/L61-Solutol(r) HS-15 showed highest dissolution. DSC thermograms
      from liquisolid formulations revealed that drug endothermic peak was disappeared
      after processing. Dissolution, DSC and FT-IR data after storage demonstrated that
      there were no significant changes in the formulations after storage. In
      conclusion, the liquid vehicles used within spironolactone liquisolid
      formulations enhanced drug dissolution rate. 

PMID- 22960708
TI  - Autobiographical memory and differentiation of schematic models in substance
      dependent patients.
AB  - BACKGROUND AND OBJECTIVES: This study aims at investigating reduced
      autobiographical memory specificity in substance-dependent patients. We examined
      whether this phenomenon is related to undifferentiated schematic models of self
      and to depression and anxiety levels. We also investigated the maintenance of
      these impairments after early clinical remission. METHODS: Seventy-three
      dependent patients (including 30 active users, 23 methadone-maintained patients,
      20 early abstinent patients) and 31 control participants were given Williams' and
      Scott's Autobiographical Memory Test (AMT) to evaluate the level of memory
      specificity. Depression and anxiety levels were assessed with the Hospital
      Anxiety and Depression Scale (HADS), and the ability of differentiation in affect
      related schematic models of self with the Level of Emotional Awareness Scale
      (LEAS). RESULTS: Dependent patients recall less specific memories than control
      individuals to the AMT. For all the participants, only the ability to
      differentiate emotional states predicts the level of specificity, whereas reduced
      specificity is not linked to depression and anxiety levels. The results also show
      that reduced specificity is still observable in methadone-maintained patients and
      in abstinent patients. LIMITATIONS: Despite the absence of difference in the
      level of memory specificity in the three groups of dependent patients, we cannot
      state that reduced memory specificity is stable over time because non-active
      consumers may not remain in remission for a long period. CONCLUSIONS: Only a lack
      of emotional differentiation seems to impede the access to specific memories in
      dependent patients and in general population. The reduced memory specificity
      observed in dependent patients seems to last after recent clinical improvement.

PMID- 22960709
TI  - The impact of social stress on self-esteem and paranoid ideation.
AB  - BACKGROUND: Vulnerability-stress models propose that social stress triggers
      psychotic episodes in high risk individuals. Previous studies found not only
      stress but also a decrease in self-esteem to precede the formation of delusions.
      As evidence for causal conclusions has not been provided yet, the present study
      assessed the direct impact of social stress on paranoid beliefs using an
      experimental design and considered a decrease in self-esteem as a mediator and
      the proneness to psychosis and paranoia as moderators of the effect. METHODS: A
      nonclinical population sample (n = 76) was randomly assigned to an experimental
      (EG) or a control group condition (CG). In the EG, participants were excluded
      during a virtual ball game (Cyberball) by the other two players and received a
      negative feedback after performing a test. The CG was included in the game and
      received a neutral feedback. Before and after the experimental conditions,
      emotions, self-esteem and paranoid beliefs were assessed using state-adapted
      questionnaires. RESULTS: After the social stress induction, the EG reported a
      higher increase in subclinical paranoid beliefs compared to the CG. The impact of
      social stress on paranoid ideation was mediated by a decrease in self-esteem and
      moderated by proneness to paranoia. Individuals who felt distressed by paranoid
      thoughts at baseline were more likely to react with an increase in paranoid
      ideation under social stress. LIMITATIONS: The results need to be confirmed in a
      patient sample to draw conclusions about the processes involved in the formation
      of delusions in clinically relevant stages. CONCLUSIONS: The impact of social
      stress on symptom formation and self-esteem is discussed in terms of recent
      models of symptom formation and interventions in psychosis.

PMID- 22960710
TI  - The value of the interview in medical student selection.

PMID- 22960711
TI  - The challenges of selecting students.

PMID- 22960712
TI  - Holding a mirror to society? The sociodemographic characteristics of the
      University of Otago's health professional students.
AB  - AIM: To describe the sociodemographic characteristics of students accepted into
      eight health professional programmes at the University of Otago. METHODS: Student
      data were obtained from the University of Otago's central student records system.
      Data were obtained in anonymous, summary form. New Zealand population data were
      obtained from Statistics New Zealand. Descriptive statistics were calculated.
      RESULTS: In 2010 health professional students at the University of Otago were
      largely from outside the Otago region (88.1%). 59.6% were female and 84.8% were
      either New Zealand citizens or permanent residents. Within the domestic student
      cohort, 65.0% of students self-identified as being within the New Zealand
      European and Other category (compared with 75.3% of the national population),
      34.2% as Asian (compared with 11.1%), 6.3% as Maori (compared with 15.2%), and
      2.3% as Pacific (compared with 7.7%). A large proportion of students came from
      high socioeconomic areas and only 3.4% of students had attended secondary schools
      with a socioeconomic decile of less than 4. CONCLUSION: Schools and Faculties
      within the University of Otago's Division of Health Sciences do not achieve the
      sociodemographic mirror of society we hope for, and we strive to improve both our
      selection processes, within the constraints and limitations of the available
      selection tools, and our student support mechanisms. We will continue to refine
      these policies and work with other key stakeholders in better preparing school
      leavers for health professional programmes.

PMID- 22960713
TI  - Students' perceptions of the Undergraduate Medicine and Health Sciences
      Admissions Test (UMAT).
AB  - AIM: Medical schools are still evaluating the place of general cognitive tests in
      medical student selection. This study explored medical student perceptions of
      UMAT, and how they prepared for taking the test. METHOD: Medical students at The
      University of Auckland and University of Otago in New Zealand were invited to
      complete a mixed-modality survey. RESULTS: Students had reservations, with 56%
      reporting UMAT is not an important test for medical students' selection and 67%
      that it is not a fair test. Eighty-one percent believe it is a stressful or very
      stressful test. The degree of importance or stress related to the weighting of
      UMAT in selection decisions. More than half of students spent more than $100 on
      books and $400 on courses to prepare for UMAT, in addition to the costs of
      sitting the test. CONCLUSION: At present, the majority of medical students in New
      Zealand who responded to the survey do not see UMAT as an acceptable test of non
      cognitive attributes. It is costly to students and also stressful.

PMID- 22960714
TI  - Using real-time ultrasound to teach living anatomy: an alternative model for
      large classes.
AB  - AIMS: Ultrasound is a safe, non-invasive and versatile imaging modality used
      widely in clinical practice. Several studies have reported using ultrasound
      imaging to supplement teaching of clinical anatomy to medical students but most
      have attempted to teach basic ultrasound skills in addition to normal sonographic
      anatomy. These small group teaching sessions are labour intensive and need
      appropriate resourcing of equipment and personnel. We report experience of an
      alternative approach suitable for large classes with more limited resources.
      METHODS: A single 1-hour ultrasound demonstration of 'living anatomy' of the
      abdomen, pelvis and neck was conducted using a young female model as the subject.
      Scans were performed by an experienced sonographer with images projected on to a
      large lecture theatre screen; medical student interaction was encouraged by two
      clinical anatomists. RESULTS: Anonymous evaluation of 152 returned questionnaires
      (greater than and equal to 63% response rate) showed that more than 80% of
      respondents considered the session had stimulated and improved their
      understanding of anatomy. CONCLUSIONS: Whilst this method of teaching anatomy
      using ultrasound does not offer hands-on experience, it does provide students
      with an introduction to the clinical utility of ultrasound and, by focusing on
      anatomic findings rather than the acquisition of technical imaging skills,
      reinforces the learning of clinical anatomy.

PMID- 22960715
TI  - Time to "refine" clinical ward assessments? Or time to retrain?
AB  - AIM: To investigate the reliability and intra-professional variation of senior
      and junior doctors in the assessment of a junior doctor's clinical skills via
      video simulation. METHODS: Simulation video was created showing 4 clinical
      scenarios. This video was shown to consultants, registrars and junior doctors in
      various forms at Auckland City Hospital. Participants evaluated each scenario
      against a modified version of the current assessment form used by the Medical
      Council of New Zealand. RESULTS: 103 Respondents completed the survey: 22 Senior
      Medical Officers, 17 registrars (PGY3+), 43 junior doctors (PGY1-2) and 21
      undergraduates (medical students). Statistical significance between groups was
      reached only for Question 6 in which Senior Medical Officers rated communication
      skills and respect for patients lower than postgraduate students (p=0.005). Large
      variability was noted in ratings for 'presentation of history' and 'clinical
      knowledge'. CONCLUSION: There is marked variation between Senior Medical Officers
      in the assessment of a junior doctor's clinical practice as demonstrated by the
      use of a simulation video. This variation is of potential major concern. Quality
      training methods of assessors may need to be implemented for standardisation of
      assessment if a summative component exists.

PMID- 22960716
TI  - ACE inhibitor fetopathy: a case series and survey of opinion amongst New Zealand
      paediatricians, obstetricians, neonatologists, and nephrologists.
AB  - The use of ACE (angiotensin converting enzyme) inhibitors is contraindicated
      throughout pregnancy due to potential adverse effects to the developing fetus
      (fetopathy). Despite this, women continue to receive ACE inhibitors both in New
      Zealand and overseas and large scale epidemiological studies have shown cases of
      associated harm to infants.  We present three New Zealand infants with potential
      renal complications following in utero ACE inhibitor exposure including
      hypertension, renal failure and death. We also present data from an email-based
      survey of experience and opinion from relevant New Zealand specialists on how to
      best counsel women of child-bearing age regarding ACE inhibitors (quantitative
      and qualitative data). To our knowledge this is the first data published on this
      subject in New Zealand. ACE inhibitor exposure in pregnancy may result in
      potential renal, cardiac and limb complications for the developing fetus. How
      best to counsel women regarding ACE inhibitors and pregnancy remains an area for
      further discussion in New Zealand.

PMID- 22960717
TI  - Sexual health, risks, and experiences of New Zealand university students:
      findings from a national cross-sectional study.
AB  - AIM: To describe the sexual health and behaviour of university students as a
      sentinel population of young New Zealanders. METHODS: A random sample of 5770
      students aged 17-24 from universities across New Zealand were invited to
      participate in an online survey in 2009. Questions on current sexual behaviours,
      lifetime unintended pregnancies and terminations, and sexual orientation were
      included. RESULTS: 2922 students responded (51% of the sample), including 1857
      women (61% of respondents), reflecting the high proportion of women in the
      university population (57%) and higher response from women. Sixty-nine percent of
      both men and women had ever had sex. Of these, 47% reported =3 partners ever, and
      20% had =3 partners in the last 12 months, with no significant gender
      differences. Describing the last time they had sex, 58% of men and 51% of women
      reported using a condom and 38% of men and 29% of women had consumed alcohol.
      Approximately 6% of women and 5% of men reported ever having sex that resulted in
      an unintentional pregnancy. Of these pregnancies, 74% of women and 72% of men
      reported a termination while another 19% of men did not know the outcome.
      CONCLUSION: Multiple sexual partnerships were common. Condom use was uncommon and
      inversely associated with number of recent sexual partners. One in 20 students
      had or contributed to at least one unintentional pregnancy. The prevalence of
      risky sexual behaviours in this population raises concern about the number of
      students at risk of sexually transmitted infections and unintentional
      pregnancies.

PMID- 22960718
TI  - New Zealand Registration Examination (NZREX Clinical): 6 years of  experience as
      an Objective Structured Clinical Examination (OSCE).
AB  - The NZREX Clinical pathway is one of several methods by which international
      medical graduates (IMGs) may enter the New Zealand medical workforce. The NZREX
      Clinical is the clinical component of the pathway and consists of a 16-station
      OSCE. The examination has previously been held twice a year, however due to
      applicant numbers NZREX Clinical is now held 4 to 5 times a year and 28
      candidates are examined in each cohort. A comprehensive range of methods are used
      to promote validity and reliability of the examination. The mean pass rate over
      the last 5 years is 60%.

PMID- 22960719
TI  - Shedding light on the decision to retain an interview for medical student
      selection.
AB  - Medical schools need to justify their range of selection tools and processes.
      This paper describes the selection tools used at one university in New Zealand
      (Auckland), which combine a measure of academic achievement, score on a test of
      general cognitive ability, and score in a structured interview. Further, it
      describes considerations in justifying the decision to continue with an interview
      as part of the selection process. This information may be of use to stakeholders
      in the Auckland medical programme, and to other schools evaluating their
      admission tools.

PMID- 22960720
TI  - Pancreatic stone and treatment using ERCP and ESWL procedures: a case study and
      review.
AB  - INTRODUCTION: Pancreatic duct stones are found in 22 to 60% of patients with
      chronic pancreatitis (CP). The stones can lead to obstruction of the outflow of
      pancreatic secretions causing increased intraductal pressure. The pancreas is
      relatively noncompliant. Therefore the rise in intraductal pressure can induce
      tissue hypertension and ischemia. This can be a major factor causing pain in
      patients with CP. This hypothesis is supported by the observation that symptoms
      may improve following pancreatic duct drainage. CASE PRESENTATION: A 62-year-old
      woman presented with persistent epigastric pain. Investigations revealed
      calcifications within the main pancreatic duct and head of the gland. Treatment
      with endoscopic retrograde cholangiopancreatography (ERCP) and extracorporeal
      shock wave lithotripsy (ESWL) achieved a good outcome. CONCLUSION: Standard
      endoscopic removal of the stones proved impossible so treatment with ESWL was
      undertaken. Following fragmentation, the calculi and fragments passed
      spontaneously or were removed endoscopically. If pancreatic stones cannot be
      removed endoscopically, ESWL should be considered prior to surgery.

PMID- 22960721
TI  - Medical image. an unusual cause of massive splenomegaly in an adult. Gaucher's
      disease.

PMID- 22960722
TI  - Medical image. papules of unknown aetiology. Disseminated Curvularia.

PMID- 22960723
TI  - Comment on Carran and Shaw's "New Zealand Malayan war veterans' exposure to
      dibutylphthalate" article.

PMID- 22960724
TI  - Smoking around hospitals.

PMID- 22960725
TI  - Vagal nerve stimulation in New Zealand: improvement of seizure control following
      the implantation of a vagal nerve stimulator.

PMID- 22960726
TI  - Learning about public health via novels: low interest by medical students,
      especially relative to movies.

PMID- 22960727
TI  - The effect of transient loading on the performance of a mesophilic anaerobic
      contact reactor at constant feed strength.
AB  - Anaerobic contact reactor is a high rate anaerobic process consisting of an
      agitated reactor and a solids settling tank for recycling. It was proved earlier
      that this type of reactor design offers highly efficient performance in the
      conversion of organic matter to biogas. In this study, the effect of transient
      loading on reactor performance in terms of a number of key intermediates and
      parameters such as, COD removal, pH and alkalinity change, VFAs, effluent MLSS
      concentration and biogas efficiency over time was examined. For this purpose, a
      step increase of organic loading rate from 3.35kg COD/m(3)day to 15.61kg
      COD/m(3)day was employed. The hydraulic retention time decreased to a value of
      8.42h by an increase in the influent flow-rate during the transient loading. It
      was observed that the mesophilic anaerobic contact reactor (MACR) was quite
      resistant to large transient shocks. The reactor recovered back to its baseline
      performance only in 15h after the shock loading was stopped. Hence, it can be
      concluded that this type of reactor design has a high potential in treating food
      processing wastewaters with varying flow characteristics.

PMID- 22960728
TI  - Evolutionary conservation of neocortical neurogenetic program in the mammals and
      birds.
AB  - The unique innovation of the layered neocortex in mammalian evolution is believed
      to facilitate adaptive radiation of mammalian species to various ecological
      environments by furnishing high information processing ability. There are no
      transitional states from the non-mammalian simple brain to the mammalian
      multilayered neocortex, and thus it is totally a mystery so far how this brain
      structure has been acquired during evolution. In our recent study, we found the
      evidence showing that the evolutionary origin of the neocortical neuron subtypes
      predates the actual emergence of layer structure. Our comparative developmental
      analysis of the chick pallium, homologous to the mammalian neocortex, revealed
      that mammals and avians fundamentally share the neocortical neuron subtypes and
      their production mechanisms, suggesting that their common ancestor already
      possessed a similar neuronal repertory. We further demonstrated that the
      neocortical layer-specific neuron subtypes are arranged as mediolaterally
      separated domains in the chick, but not as layers in the mammalian neocortex.
      These animal group-specific neuronal arrangements are accomplished by spatial
      modulation of the neurogenetic program, suggesting an evolutionary hypothesis
      that the regulatory changes in the neurogenetic program innovated the mammalian
      specific layered neocortex. 

PMID- 22960729
TI  - Upper extremity strength characteristics in female recreational tennis players
      with and without lateral epicondylalgia.
AB  - STUDY DESIGN: Descriptive, cross-sectional. OBJECTIVES: To compare static
      strength characteristics of the upper extremity musculature in female
      recreational tennis players with lateral epicondylalgia to those of
      nonsymptomatic tennis players and a control group of women who did not play
      tennis. BACKGROUND: There is a paucity of research describing the relationship
      between lateral epicondylalgia and strength characteristics of the upper
      extremity musculature, despite the functional relationship between the shoulder,
      elbow, and wrist. METHODS: Sixty-three women were recruited into 3 groups (n = 21
      per group): symptomatic tennis players (STP) with lateral epicondylalgia,
      nonsymptomatic tennis players, and controls. Data collection was performed during
      a single session, during which the strength of selected muscle groups of the
      dominant upper extremity was measured using a combination of force transducers.
      Strength ratios of selected muscle groups were then calculated. RESULTS: The STP
      group reported median pain level of 3/10 on a numeric pain rating scale and a
      symptom duration of 16 weeks. The STP group had weaker lower trapezius strength
      (mean difference, -9.0 N; 95% confidence interval [CI]: -13.5, -4.4) and wrist
      extensor strength (-12.7 N; 95% CI: -24.4, -1.1), and a higher shoulder
      internal/external rotation strength ratio (0.19; 95% CI: 0.02, 0.35) and
      upper/lower trapezius strength ratio (1.32; 95% CI: 0.41, 2.23), compared to
      those of the nonsymptomatic group. Compared to the control group, the STP group
      demonstrated a significantly higher shoulder internal/external rotation strength
      ratio (0.21; 95% CI: 0.04, 0.38) and wrist flexion/extension strength ratio
      (0.14; 95% CI: 0.01, 0.27). CONCLUSION: In this group of recreational female
      tennis players, significant differences in strength and strength ratio
      characteristics were identified. Although the design of the study precludes
      establishing a cause-and-effect relationship, the results suggest further study
      and treatment of the muscle groups of interest.

PMID- 22960731
TI  - Factors associated with the occurrence of sentinel events during transition from
      hospital to home for individuals with traumatic brain injury.
AB  - OBJECTIVE: To describe the timing and factors associated with the occurrence of
      sentinel events (financial strain, difficulty accessing therapy, return to work,
      accommodation change and independent transport use) during transition to the
      community for individuals with traumatic brain injury. DESIGN: Longitudinal
      cohort design with data collected pre discharge and at 1, 3 and 6-month follow
      ups. SUBJECTS: Individuals with moderate to severe traumatic brain injury (n =
      127), discharged home from acute care and inpatient rehabilitation. METHODS: Data
      were collected using self-report questionnaires (sentinel events questionnaire,
      Mayo Portland Adaptability Inventory-4, Sydney Psychosocial Reintegration Scale,
      Depression Anxiety Stress Scale). Logistic regression was used to identify
      factors associated with sentinel events. RESULTS: The most commonly reported
      events were independent transport use and return to work, reported on 104 and 90
      occasions, respectively. A longer hospital stay and poorer community integration
      were related to negative events (e.g. reduced therapy). The inverse relationship
      was seen for positive events. Links existed between sentinel events (e.g.
      previous financial strain increased the likelihood of this event in transition).
      CONCLUSION: This paper highlights the interplay between personal and
      environmental factors and life events in shaping transition experiences.
      Individualised service planning and monitoring of sentinel events is important to
      promote successful community transition.

PMID- 22960730
TI  - Enhanced cell survival and diminished apoptotic response to simulated ischemia
      reperfusion in H9c2 cells by magnetic field preconditioning.
AB  - The potential for 60 Hz magnetic field (MF) preconditioning to protect heart
      derived, H9c2 cultures from damage by simulated ischemia and reperfusion (I-R)
      was examined. The most effective MF exposure conditions (120 MUT, 4-8 h)
      increased cell survival by 40-50 % over that seen with I-R alone. Potential
      targets of MF preconditioning were assessed by investigating the apoptosis
      related drop in Bcl-2 levels and elevation of the specific activities of caspases
      3, 8 and 9 produced by I-R. In response to MF exposure Bcl-2 levels rose 2 to 2.6
      fold, and caspase specific activities fell 51-72 % from the values seen after I-R
      alone. Levels of Hsp's 25, 32 and 72 were examined in response to the MF, but
      showed little-to-no elevation beyond that produced by I-R. However, MF
      preconditioning produced a 77 % decrease in the I-R-induced translocation of
      phosphorylated Hsp25 (Hsp25-P) from the cytosolic to the nuclear-cytoskeletal
      cell fraction. This might protect by maintaining active Hsp25-P in the cytosol to
      function as a chaperone or to bind cytochrome c. Blocking Hsp25 phosphorylation
      with SB203580, an inhibitor of p38 MAPK, resulted in increases of 64 and 80 % in
      the respective specific activities of caspases 3 and 9 in cells subjected to I-R,
      and eliminated the MF-induced reduction in caspase 3 activity.

PMID- 22960732
TI  - All-optical microfluidic chips for reconfigurable dielectrophoretic trapping
      through SLM light induced patterning.
AB  - We explore a novel approach for fabricating polymeric microfluidic-channelled
      dielectrophoretic (DEP) chips by direct laser projection through a holographic
      Spatial-Light-Modulator (SLM) onto photorefractive crystal substrates. As the
      first step, an all-optical mould-free approach was used to fabricate the PDMS
      microfluidic channel, by exploiting the light induced space charge field in Fe
      doped lithium niobate crystals, with the aim of integrating a microfluidic
      channel directly onto the functionalized substrate. Subsequently, as the second
      step, geometrical flexible DEP traps can be created onto the substrate by the
      same SLM holographic projection system. The experimental verification shows the
      trapping of flowing carbon nanotubes (CNTs) and the formation of chaining effects
      with graphite nanofibers. The main feature of the SLM is the ability to display
      an arbitrary light intensity pattern that is used here for fabricating the
      channels. Moreover, the reconfigurable trapping of CNTs is possible simply by the
      optical writing/erasing of various light intensity patterns projected by the SLM.

PMID- 22960734
TI  - Quantification of tenofovir in human plasma by solid-phase extraction and high
      performance liquid chromatography coupled with UV detection.
AB  - BACKGROUND: Tenofovir is used in the treatment of HIV and hepatitis virus
      infections. The aim of this work was to develop and validate an high-performance
      liquid chromatography coupled with ultraviolet detection assay that can be
      implemented in most laboratories for the purposes of therapeutic drug monitoring
      and pharmacokinetic studies. METHODS: Two hundred microliters of plasma sample
      was used for the assay. Sample processing was carried out with solid-phase
      extraction. Tegafur was used as the internal standard. The chromatographic
      separation was achieved on a C18 reverse-phase analytic column with a mobile
      phase consisting of sodium phosphate buffer (pH: 6.12; 20.0 mM)-acetonitrile
      tetrabutylammonium hydroxide solution (pH: 13.64; 1.14 mM) (90.0:10.0:0.3,
      v/v/v). The detection was at 262 nm, and the column oven was set at 35 degrees C.
      RESULTS: The linear range of the calibration curve was 20-2000 ng/mL (r > 0.999,
      n = 6). The absolute extraction recoveries were 97.4% +/- 2.5% and 81.6% +/- 0.8%
      for tenofovir and tegafur, respectively. The relative standard deviations were
      2.3%-3.3% for the intraday and 2.8%-5.3% for the interday analyses. The accuracy
      was within 100% +/- 7%. The successful application of this method in a
      pharmacokinetic study in Chinese HIV-infected patients confirmed its robustness
      and reliability. CONCLUSIONS: A validated and reproducible method has been
      established to quantify the concentration of tenofovir in human plasma by high
      performance liquid chromatography coupled with ultraviolet detection.

PMID- 22960736
TI  - Safe and effective variability-a criterion for dose individualization.
AB  - BACKGROUND: A primary goal of clinical pharmacology is to understand the factors
      that determine the dose-effect relationship and to use this knowledge to
      individualize drug dose. METHODS: A principle-based criterion is proposed for
      deciding among alternative individualization methods. RESULTS: Safe and effective
      variability defines the maximum acceptable population variability in drug
      concentration around the population average. CONCLUSIONS: A decision on whether
      patient covariates alone are sufficient, or whether therapeutic drug monitoring
      in combination with target concentration intervention is needed, can be made by
      comparing the remaining population variability after a particular dosing method
      with the safe and effective variability.

PMID- 22960737
TI  - Nicotine-replacement therapy in pregnancy-the end of the road?
AB  - Smoking in pregnancy is associated with serious perinatal risks, leading to
      attempts to prevent smoking with the use of nicotine-replacement therapy (NRT).
      After more than a decade of studies failing to show the effectiveness of NRT for
      smoking cessation in pregnancy, a recent large, randomized trial has clearly
      shown that the failure may be caused by >90% dropout rate. Several secondary
      analyses of randomized trials have shown that NRT is efficacious in decreasing
      smoking in pregnancy and in optimizing fetal growth among women who take the
      product. But to be effective in smoking cessation, any drug has to be taken by
      the patients. Can we overcome the dismal rates of pregnant women's adherence to
      NRT, so we can save unborn babies from the serious risks associated with their
      mothers' smoking?

PMID- 22960738
TI  - Metabolic module mining based on Independent Component Analysis in Arabidopsis
      thaliana.
AB  - Independent Component Analysis (ICA) has been introduced as one of the useful
      tools for gene-functional discovery in animals. However, this approach has been
      poorly utilized in the plant sciences. In the present study, we have exploited
      ICA combined with pathway enrichment analysis to address the statistical
      challenges associated with genome-wide analysis in plant system. To generate an
      Arabidopsis metabolic platform, we collected 4,373 Affy-metrix ATH1 microarray
      datasets. Out of the 3,232 metabolic genes and transcription factors, 99.47% of
      these genes were identified in at least one component, indicating the coverage of
      most of the metabolic pathways by the components. During the metabolic pathway
      enrichment analysis, we found components that indicate an independent regulation
      between the isoprenoid biosynthesis pathways. We also utilized this analysis tool
      to investigate some transcription factors involved in secondary cell wall
      biogenesis. This approach has identified remarkably more transcription factors
      compared to previously reported analysis tools. A website providing user-friendly
      searching and downloading of the entire dataset analyzed by ICA is available at
      http://kimjy.gnu.ac.kr/ICA.files/slide0002.htm . ICA combined with pathway
      enrichment analysis might provide a powerful approach for the extraction of the
      components responsible for a biological process of interest in plant systems.

PMID- 22960739
TI  - Visible effects of rapamycin (sirolimus) on human skin explants in vitro.
AB  - In this manuscript, we report observations of the effects of rapamycin in an
      organotypic culture of human skin explants. The tissues were cultured for 5 days
      at the air-liquid interface or in submersed conditions with media with and
      without rapamycin at 2 nM concentration. Histological analysis of tissue sections
      indicated that rapamycin-treated samples maintained a better epidermal structure
      in the upper layers of the tissue than untreated samples, mostly evident when
      skin was cultured in submersed conditions. A significant decrease in the number
      of positive proliferative cells using the Ki67 antigen was observed when
      specimens were treated with rapamycin, in both air-liquid and submersed
      conditions but apoptosis differences between treated and untreated specimens, as
      seen by cleaved caspase-3 positive cells, were only observed in submersed
      specimens. Finally, a decrease and variability in the location in the expression
      of the differentiation marker involucrin and in E-cadherin were also evident in
      submersed samples. These results suggest that the development of topical
      applications containing rapamycin, instead of systemic delivery, may be a useful
      tool in the treatment of skin diseases that require reduction of proliferation
      and modulation or control of keratinocyte differentiation.

PMID- 22960740
TI  - [Protein Z deficiency in unexplained affinity to thromboses, bleedings or
      abortions].
AB  - A protein Z deficiency is presumably related with a threefold risk of venous and
      arterial thrombosis. Mucosal bleedings and post-operative haematomas can occur
      more frequently. This is seen in an increased in vivo bleeding time without other
      plasmatic coagulation disorders or thrombopathies. Pregnancy complications,
      especially abortions before the 15th week of gestation, are described as well.
      PATIENTS, METHODS: Since May 2011 the plasmatic concentration of protein Z has
      been tested in 684 patients of the Hamostaseologicum. RESULTS: In 74 patients a
      protein Z deficiency has been found. In other 45 patients protein Z was reduced
      because of the intake of phenprocoumon or coumadin. Of the 74 patients with
      diminished protein Z concentration 39 were marginally decreased (protein Z 1000
      1500 ug/l). Of the 35 patients with a protein Z concentration <1000 ug/l 12 had
      had a thrombosis before (6 strokes, 3 DVT or PE, 1 arterial thrombosis, 1 retinal
      branch vein occlusion, 1 acute hearing loss). 7 had arterial hypertension, 2
      suffered from diabetes mellitus. Of the patients who had a thrombosis 6 had a
      heterozygous factor V Leiden mutation. 10 had a microcirculation disorder
      (Raynaud's phenomenon), 4 had had bleeding complications before, 3 had a von
      Willebrand disease type I, 6 patients had had abortions and 4 were healthy. Of
      the 39 patients with protein Z concentrations between 1000 and 1500 ug/l 18 had
      experienced a thrombosis before (9 DVT or PE, 3 myocardial infarctions, 1 CHD, 3
      strokes, 1 retinal branch vein occlusion, 1 PAOD I, 1 tinnitus). 5 additionally
      had arterial hypertension. 13 suffered from Raynaud's phenomenon, of which 7 had
      a hypotension. Of the patients with thromboses 3 had a heterozygous factor V
      Leiden mutation and one a protein C deficiency. 7 patients had had an abortion
      before. Bleeding complications were seen in 4 patients, of which 3 suffered from
      von Willebrand disease type 1.

PMID- 22960741
TI  - Anion dependence in the spin-crossover properties of a Fe(II) podand complex.
AB  - We report the syntheses, characterisations, and spin state behaviours of salts of
      the tripodal-ligated Fe(II) complex [FeL(6-OH)]X(2) (L(6-OH) = tris{4-[(6
      methanol)-2-pyridyl]-3-aza-3-butenyl}amine, X = OTf(-) (1), Br(-) (2), I(-) (3),
      BPh(4)(-) (4)). Covalent linking of the ligand arms is imperative as a high-spin
      bis(tridentate) complex (5) is formed when a non-tethered ethyl iminopyridine
      ligand (L(2) = 4-[(6-methanol)-2-pyridyl]-3-aza-3-butenyl) is used. For salts 1
      4, thermally-induced spin-crossover (SCO) is observed in the solid state, with
      dependence on anion and solvate molecules. Salts with larger anions show more
      complete SCO centred at higher temperatures (1 > 3 > 2); the triflate salt 1
      (T(1/2) = 173 K) also shows the strongest cooperativity of the compounds
      examined. Hydrogen bonding appears to be critical to SCO in this family of salts:
      limiting interactions by use of tetraphenylborate produces a high-spin complex
      down to 5 K. In protic solvents such as methanol, spectra of [FeL(6-OH)](2+) are
      largely unchanged over a period of three days, but dissociate when interrogated
      with strong field bidentate ligands. Compounds 1-3, and 5 remain high spin in
      solution down to 180 K, consistent with the data obtained in the solid state.

PMID- 22960742
TI  - p21-activated kinase 4 regulates mitotic spindle positioning and orientation.
AB  - During mitosis, microtubules (MTs) are massively rearranged into three sets of
      highly dynamic MTs that are nucleated from the centrosomes to form the mitotic
      spindle. Tight regulation of spindle positioning in the dividing cell and
      chromosome alignment at the center of the metaphase spindle are required to
      ensure perfect chromosome segregation and to position the cytokinetic furrow that
      will specify the two daughter cells. Spindle positioning requires regulation of
      MT dynamics, involving depolymerase activities together with cortical and
      kinetochore-mediated pushing and pulling forces acting on astral MTs and
      kinetochore fibres. These forces rely on MT motor activities. Cortical pulling
      forces exerted on astral MTs depend upon dynein/dynactin complexes and are
      essential in both symmetric and asymmetric cell division. A well-established
      spindle positioning pathway regulating the cortical targeting of dynein/dynactin
      involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA
      (microtubule binding nuclear mitotic apparatus protein) complex. Spindle
      orientation is also regulated by integrin-mediated cell adhesion and actin
      retraction fibres that respond to mechanical stress and are influenced by the
      microenvironment of the dividing cell. Altering the capture of astral MTs or
      modulating pulling forces affects spindle position, which can impair cell
      division, differentiation and embryogenesis. In this general scheme, the activity
      of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial.
      Recently, the p21-activated kinases (PAKs) emerged as novel important players in
      mitotic progression. In our recent article, we demonstrated that PAK4 regulates
      spindle positioning in symmetric cell division. In this commentary, and in light
      of recent published studies, we discuss how PAK4 could participate in the
      regulation of mechanisms involved in spindle positioning and orientation.

PMID- 22960743
TI  - The Fun30 nucleosome remodeller promotes resection of DNA double-strand break
      ends.
AB  - Chromosomal double-strand breaks (DSBs) are resected by 5' nucleases to form 3'
      single-stranded DNA substrates for binding by homologous recombination and DNA
      damage checkpoint proteins. Two redundant pathways of extensive resection have
      been described both in cells and in vitro, one relying on Exo1 exonuclease and
      the other on Sgs1 helicase and Dna2 nuclease. However, it remains unknown how
      resection proceeds within the context of chromatin, where histones and histone
      bound proteins represent barriers for resection enzymes. Here we identify the
      yeast nucleosome-remodelling enzyme Fun30 as a factor promoting DSB end
      resection. Fun30 is the major nucleosome remodeller promoting extensive Exo1- and
      Sgs1-dependent resection of DSBs. The RSC and INO80 chromatin-remodelling
      complexes and Fun30 have redundant roles in resection adjacent to DSB ends.
      ATPase and helicase domains of Fun30, which are needed for nucleosome
      remodelling, are also required for resection. Fun30 is robustly recruited to DNA
      breaks and spreads along the DSB coincident with resection. Fun30 becomes less
      important for resection in the absence of the histone-bound Rad9 checkpoint
      adaptor protein known to block 5' strand processing and in the absence of either
      histone H3 K79 methylation or gamma-H2A, which mediate recruitment of Rad9 (refs
      9, 10). Together these data suggest that Fun30 helps to overcome the inhibitory
      effect of Rad9 on DNA resection.

PMID- 22960744
TI  - The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end
      resection.
AB  - Several homology-dependent pathways can repair potentially lethal DNA double
      strand breaks (DSBs). The first step common to all homologous recombination
      reactions is the 5'-3' degradation of DSB ends that yields the 3' single-stranded
      DNA required for the loading of checkpoint and recombination proteins. In yeast,
      the Mre11-Rad50-Xrs2 complex (Xrs2 is known as NBN or NBS1 in humans) and Sae2
      (known as RBBP8 or CTIP in humans) initiate end resection, whereas long-range
      resection depends on the exonuclease Exo1, or the helicase-topoisomerase complex
      Sgs1-Top3-Rmi1 together with the endonuclease Dna2 (refs 1-6). DSBs occur in the
      context of chromatin, but how the resection machinery navigates through
      nucleosomal DNA is a process that is not well understood. Here we show that the
      yeast Saccharomyces cerevisiae Fun30 protein and its human counterpart SMARCAD1
      (ref. 8), two poorly characterized ATP-dependent chromatin remodellers of the
      Snf2 ATPase family, are directly involved in the DSB response. Fun30 physically
      associates with DSB ends and directly promotes both Exo1- and Sgs1-dependent end
      resection through a mechanism involving its ATPase activity. The function of
      Fun30 in resection facilitates the repair of camptothecin-induced DNA lesions,
      although it becomes dispensable when Exo1 is ectopically overexpressed.
      Interestingly, SMARCAD1 is also recruited to DSBs, and the kinetics of
      recruitment is similar to that of EXO1. The loss of SMARCAD1 impairs end
      resection and recombinational DNA repair, and renders cells hypersensitive to DNA
      damage resulting from camptothecin or poly(ADP-ribose) polymerase inhibitor
      treatments. These findings unveil an evolutionarily conserved role for the Fun30
      and SMARCAD1 chromatin remodellers in controlling end resection, homologous
      recombination and genome stability in the context of chromatin.

PMID- 22960746
TI  - Initiation of transcription-coupled repair characterized at single-molecule
      resolution.
AB  - Transcription-coupled DNA repair uses components of the transcription machinery
      to identify DNA lesions and initiate their repair. These repair pathways are
      complex, so their mechanistic features remain poorly understood. Bacterial
      transcription-coupled repair is initiated when RNA polymerase stalled at a DNA
      lesion is removed by Mfd, an ATP-dependent DNA translocase. Here we use single
      molecule DNA nanomanipulation to observe the dynamic interactions of Escherichia
      coli Mfd with RNA polymerase elongation complexes stalled by a cyclopyrimidine
      dimer or by nucleotide starvation. We show that Mfd acts by catalysing two
      irreversible, ATP-dependent transitions with different structural, kinetic and
      mechanistic features. Mfd remains bound to the DNA in a long-lived complex that
      could act as a marker for sites of DNA damage, directing assembly of subsequent
      DNA repair factors. These results provide a framework for considering the
      kinetics of transcription-coupled repair in vivo, and open the way to
      reconstruction of complete DNA repair pathways at single-molecule resolution.

PMID- 22960747
TI  - The influence of internal and skin temperatures on active cutaneous vasodilation
      under different levels of exercise and ambient temperatures in humans.
AB  - To clarify the influence of internal and skin temperature on the active cutaneous
      vasodilation during exercise, the body temperature thresholds for the onset of
      active vasodilation during light or moderate exercise under different ambient
      temperature conditions were compared. Seven male subjects performed 30 min of a
      cycling exercise at 20 % or 50 % of peak oxygen uptake in a room maintained at
      20, 24, or 28  degrees C. Esophageal (Tes) and mean skin temperature (Tsk) as
      measured by a thermocouple, deep thigh temperature (Tdt) by the zero-heat-flow
      (ZHF) method, and forearm skin blood flow by laser-Doppler flowmetry (LDF) were
      monitored. The mean arterial pressure (MAP) was also monitored non-invasively,
      and the cutaneous vascular conductance (CVC) was calculated as the LDF/MAP.
      Throughout the experiment, the Tsk at ambient temperatures of 20, 24, and 28 
      degrees C were approximately 30, 32, and 34  degrees C, respectively, for both 20
      % and 50 % exercise. During 50 % exercise, the Tes or Tdt thresholds for the
      onset of the increase in CVC were observed to be similar among the 20, 24, and 28
      degrees C ambient conditions. During 20 % exercise, the increase in Tes and Tdt
      was significantly lower than those found at 50 %, and the onset of the increase
      in CVC was only observed at 28  degrees C. These results suggest that the onset
      of active vasodilation was affected more strongly by the internal or exercising
      tissue temperatures than by the skin temperatures during exercise performed at a
      moderate load in comparison to a light load under Tsk variations ranging from 30 
      degrees C to 34  degrees C. Therefore, the modification by skin temperature of
      the central control on cutaneous vasomotor tone during exercise may differ
      between different exercise loads.

PMID- 22960748
TI  - Influence of seasonal weather and climate variability on crop yields in Scotland.
AB  - The climatic sensitivity of four important agriculture crops (wheat, barley,
      oats, potatoes) in a northern temperate bioclimatic region is investigated using
      national-level yield data for 1963-2005. The climate variables include monthly
      and annual meteorological data, derived bioclimatic metrics, and the North
      Atlantic Oscillation index. Statistical analysis shows that significant
      relationships between yield and climate vary depending on the crop type and month
      but highlight the influence of precipitation (negative correlation) and sunshine
      duration (positive correlation) rather than temperature. Soil moisture deficit is
      shown to be a particular useful indicator of yield with drier summers providing
      the best yields for Scotland as a whole. It is also tentatively inferred that the
      sensitivity of these crops, particularly wheat and barley, to soil moisture
      deficits has increased in recent years. This suggests that improved crop yields
      are optimised for dry sunny years despite the continued prevalence of
      considerable inter-annual variability in seasonal weather.

PMID- 22960749
TI  - Melatonin administration differentially affects age-induced alterations in daily
      rhythms of lipid peroxidation and antioxidant enzymes in male rat liver.
AB  - A central clock/pacemaker, suprachiasmatic nuclei of the hypothalamus coordinates
      and entrains circadian oscillations in the peripheral tissues such as the liver,
      kidney, heart, lungs etc. called peripheral clocks. These also have endogenous
      circadian oscillations. The circadian rhythms of antioxidants present in cytosol
      signify redox state of the cell during day/night cycle. The liver has a major
      impact on homeostasis through its control on serum protein composition and plays
      a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic
      waste products and undergoes substantial changes in structure and function upon
      aging. In present study, the temporal patterns of oxidative stress indicators in
      liver were studied. Daily rhythms of lipid peroxidation end products, reduced
      glutathione (GSH), oxidized glutathione (GSSG) and antioxidant enzymes such as
      glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were
      studied in liver at variable time points (Zeitgeber Time (ZT) 0, 6, 12 and 18) in
      three age groups: 3 (adult), 12 and 24 months old male Wistar rats. There was
      increase in oxidative stress in 12 and 24 months old rats indicated through a
      significant increase in lipid peroxidation, decrease in GSH/GSSG ratio and
      antioxidant enzyme activities. In 3 months old rats, lipid peroxidation was
      maximum at ZT-12 whereas GSH, SOD and CAT activities were minimum at ZT-12. The
      maximum level in 24 h i.e., acrophases of lipid peroxidation, GPx, SOD and CAT
      activities in liver cell free extracts altered upon aging. As melatonin,
      messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and
      an antiaging drug, declines with aging we studied the effects of melatonin on
      activities of these antioxidant enzymes in aging rats. Melatonin administration
      resulted in differential restoration of acrophases, amplitude, mean as well as
      daily rhythms of lipid peroxidation and antioxidants in liver of 12 and 24 months
      old rats.

PMID- 22960750
TI  - Physiology declines prior to death in Drosophila melanogaster.
AB  - For a period of 6-15 days prior to death, the fecundity and virility of
      Drosophila melanogaster fall significantly below those of same-aged flies that
      are not near death. It is likely that other aspects of physiology may decline
      during this period. This study attempts to document changes in two physiological
      characteristics prior to death: desiccation resistance and time-in-motion. Using
      individual fecundity estimates and previously described models, it is possible to
      accurately predict which flies in a population are near death at any given age;
      these flies are said to be in the "death spiral". In this study of approximately
      7,600 females, we used cohort mortality data and individual fecundity estimates
      to dichotomize each of five replicate populations of same-aged D. melanogaster
      into "death spiral" and "non-spiral" groups. We then compared these groups for
      two physiological characteristics that decline during aging. We describe the
      statistical properties of a new multivariate test statistic that allows us to
      compare the desiccation resistance and time-in-motion for two populations chosen
      on the basis of their fecundity. This multivariate representation of the
      desiccation resistance and time-in-motion of spiral and non-spiral females was
      shown to be significantly different with the spiral females characterized by
      lower desiccation resistance and time spent in motion. Our results suggest that
      D. melanogaster may be used as a model organism to study physiological changes
      that occur when death is imminent.

PMID- 22960751
TI  - Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in
      vivo.
AB  - Neuroblastoma (NB) is a type of tumor usually found in children under 5 years of
      age, which originates from lesions in the nervous system and has fast growth and
      early transformation characteristics. Similar to other cancer types, some typical
      tumor suppressor genes (TSGs), such as P53 and CHD5 are silenced in NB because of
      high methylation at promoter zones. In the present study, our results showed that
      genistein, an element found in soy, is an epigenetic modifier able to decrease
      hypermethylation levels of CHD5, and enhances the expression of CHD5 as well as
      p53, possibly contributing to inhibition of NB growth in vivo and tumor
      microvessel formation. Furthermore, genistein acts as a DNA methyltransferase
      (DNMT) inhibitor to significantly decrease the expression of DNMT3b. Our study
      indicates that genistein plays an important role in inhibiting NB growth in vivo,
      probably preventing tumorigenesis risk as a kind of therapeutic agent for NB
      treatment in the future.

PMID- 22960752
TI  - Bimodal binding and free energy of the progesterone receptor in the induction of
      female sexual receptivity by progesterone and synthetic progestins.
AB  - Synthetic progestins (SPs) are used for regulation of fertility, contraception
      and hormone replacement therapy. The acetylated medroxyprogesterone (MPA),
      megestrol (MGA) and chlormadinone (CLA) are related to progesterone (P). Other
      SPs are 19-nortestosterone derivatives such as: norethisterone (NET),
      norethynodrel (NED) or the 13-ethyl gonane, levonorgestrel (LNG). We studied MPA,
      NET, NED and LNG in a dose-response manner to induce sexual receptivity in rats.
      Results showed that MPA, NET and NED act as partial agonists, with similar or
      lower potency than P. However, LNG is a full agonist. Additionally, the molecules
      of MPA, MGA, CLA, NET, NED, LNG, and P, were submitted to computer calculations
      at ab initio quantum mechanics theory, to obtain their electronic structure and
      molecular properties. The aim was to correlate their behavioral effect with their
      physicochemical properties. In addition, the crystals of P, NET and LNG bound to
      the progesterone receptor (PR) were studied. The PR crystallizes as a dimer
      forming two monomers (mA and mB), in which Gln725 interacts in either of two
      possible ways with the C3-carbonyl pharmacophore of progestins. P binds
      differentially to both PR monomers, while NET binds exclusively as mA and LNG
      binds only as mB in both monomers with no difference. Energetically, binding of
      LNG and P to mB, is more favorable than that of NET and P to mA. Consequently,
      this bimodal mechanism increases the action possibilities of SPs on biological
      systems. Interestingly, progestin potency depends mostly on local molecular
      structure and electronic features, prevailing over total molecular properties.

PMID- 22960753
TI  - First information parents receive after UNHS detection of their baby's hearing
      loss.
AB  - The first information parents receive after referral through Universal Newborn
      Hearing Screening (UNHS) has significant consequences for later care-related
      decisions they take and thus for the future of the child with a hearing loss. In
      this study, 11 interviews were conducted with a representative sample of Flemish
      service providers to discover (a) the content of the information provided to
      parents and (b) the service providers' assumptions and beliefs concerning
      deafness and care. To do this, we conducted an interpretative phenomenological
      analysis, followed by a discourse analysis. Results showed that parents receive
      diverse information, depending on the reference center to which they are
      referred. Moreover, all service providers used a medical discourse. We suggest
      that there is value to be gained from closer consideration of the nature of
      follow-up services provided in response to UNHS in Flanders and from auditing the
      professional preparation of service providers that are involved in providing
      information to parents.

PMID- 22960754
TI  - Assistive hearing technologies among students with hearing impairment: factors
      that promote satisfaction.
AB  - Hearing technology can play an essential part in the education of deaf and hard
      of-hearing children in inclusive schools. Few studies have examined these
      children's experiences with this technology. This article explores factors
      pertaining to children's use of and attitudes toward hearing technologies, such
      as hearing aids, cochlear implants, teacher-worn microphones, and student-worn
      microphones. The study included 153 deaf and hard-of-hearing students. All
      students communicated orally and were in inclusive schools from grades 5-10. The
      results suggest that males view hearing technology more positively than do
      females. Having severe hearing loss also promoted positive attitudes toward
      hearing aids and cochlear implants, but not toward microphones. The students with
      positive self-descriptions tended to be more satisfied with hearing aids or
      cochlear implants than the students with negative self-descriptions. The main
      factors promoting the use of hearing aids were severe hearing loss, positive
      attitudes toward hearing aids, and the sound quality of hearing aids.

PMID- 22960745
TI  - Comprehensive genomic characterization of squamous cell lung cancers.
AB  - Lung squamous cell carcinoma is a common type of lung cancer, causing
      approximately 400,000 deaths per year worldwide. Genomic alterations in squamous
      cell lung cancers have not been comprehensively characterized, and no molecularly
      targeted agents have been specifically developed for its treatment. As part of
      The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to
      provide a comprehensive landscape of genomic and epigenomic alterations. We show
      that the tumour type is characterized by complex genomic alterations, with a mean
      of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy
      number alteration per tumour. We find statistically recurrent mutations in 11
      genes, including mutation of TP53 in nearly all specimens. Previously unreported
      loss-of-function mutations are seen in the HLA-A class I major histocompatibility
      gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous
      differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in
      47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic
      target in most tumours, offering new avenues of investigation for the treatment
      of squamous cell lung cancers.

PMID- 22960756
TI  - Roles of Arabidopsis bax inhibitor-1 in delaying methyl jasmonate-induced leaf
      senescence.
AB  - Previous studies have reported that methyl jasmonate (MeJA) can promote plant
      senescence. Arabidopsis thaliana BI1 (AtBI1) participates in leaf senescence and
      JA signal pathway. Our recent report has suggested that AtBI1 plays a crucial
      role in MeJA-induced leaf senescence. Concomitantly, cytosolic calcium
      ([Ca2+]cyt) and MPK6, a mitogen-activated protein kinase (MAPK), participate in
      the process of MeJA-induced leaf senescence. And AtBI1 might play its roles in
      delaying MeJA-induced leaf senescence by suppressing the [Ca2+]cyt-dependent
      activation of MPK6. Our study contributes to the understanding of the function
      and mechanism of AtBI1 in plant senescence. Though some of signaling molecules
      have been elucidated in this type of plant senescence, the mechanism of AtBI-1
      functions in reducing the [Ca2+]cyt during MeJA-induced leaf senescence needs
      further improvement, and the source and location of Ca2+ are still not clear
      enough. By using the Arabidopsis and MeJA as the research model, the subsequent
      researches have been performed to investigate the upstream regulation and
      downstream function of Ca2+ in this type of plant senescence.

PMID- 22960757
TI  - Is polyphenol induction simply a result of altered carbon and nitrogen
      accumulation?
AB  - Carbon translocation in plants is shaped by phyllotaxis and regulated by
      source/sink interactions that respond to the demands of growth and defense. We
      have studied this extensively in poplar saplings, and recently showed that unlike
      carbon import, nitrogen is not translocated to sink leaves in response to
      application of jasmonic acid. Here we report that this is also true for young
      trees in the field. We discuss the importance of transport processes in
      establishing local C:N ratios, and suggest that the JA-induced flow of C but not
      N to sink tissues, and their corresponding increases in C-based defenses, may
      simply reflect a plant adaptation to handle excess reduced carbon and energy.

PMID- 22960755
TI  - Multi-level regulation of cellular recognition of viral dsRNA.
AB  - Effective antiviral immunity depends on accurate recognition of viral RNAs by the
      innate immune system. Double-stranded RNA (dsRNA) often accumulates in virally
      infected cells and was initially considered a unique viral signature that was
      sufficient to initiate antiviral response through dsRNA receptors and dsRNA
      dependent effectors such as Toll-like receptor 3, retinoic acid inducible gene-1,
      protein kinase RNA-activated and oligoadenylate synthetase. However, dsRNA is
      also present in many cellular RNAs, raising a question of how these receptors and
      effectors discriminate between viral and cellular dsRNAs. Accumulating evidence
      suggests that innate immune sensors detect not only dsRNA structure but also
      other and often multiple features of RNA such as length, sequence, cellular
      location, post-transcriptional processing and modification, which are divergent
      between viral and cellular RNAs. This review summarizes recent findings on the
      substrate specificities of a few selected dsRNA-dependent effectors and
      receptors, which have revealed more complex mechanisms involved in cellular
      discrimination between self and non-self RNA.

PMID- 22960758
TI  - The maize cystatin CC9 interacts with apoplastic cysteine proteases.
AB  - In a recent study we identified corn cystain9 (CC9) as a novel compatibility
      factor for the interaction of the biotrophic smut fungus Ustilago maydis with its
      host plant maize. CC9 is transcriptionally induced during the compatible
      interaction with U. maydis and localizes in the maize apoplast where it inhibits
      apoplastic papain-like cysteine proteases. The proteases are activated during
      incompatible interaction and salicylic acid (SA) treatment and, in turn, are
      sufficient to induce SA signaling including PR-gene expression. Therefore the
      inhibition of apoplastic papain-like cysteine proteases by CC9 is essential to
      suppress host immunity during U. maydis infection. Here were present new
      experimental data on the cysteine protease-cystatin interaction and provide an in
      silco analysis of plant cystatins and the identified apoplastic cysteine
      proteases.

PMID- 22960759
TI  - Reduction of 13 kD prolamins increases recombinant protein yield and recovery
      rate in rice endosperm.
AB  - RNA silencing inducible sequence (RSIS) causes post-transcriptional gene
      silencing (PTGS) of 5' or 3' flanking sequence-containing genes by inhibiting
      proper transcriptional termination. Exploiting this nature, 13 kD Pro-less, in
      which major seed storage protein (SSP) 13 kD prolamins are reduced, has been
      generated. In 13 kD Pro-less, other SSPs, such as glutelins, are increased as a
      compensation effect to maintain amino acid pool. 7Crp is the seven-linked epitope
      peptide derived from major cedar pollen allergens Cry j 1 and Cry j 2. When 7Crp
      is expressed in 13 kD Pro-less endosperm, accumulation level of 7Crp increased.
      Furthermore, recovery rate of 7Crp without reducing reagent increased. These
      findings indicate that 13 kD Pro-less endosperm provides a good production
      platform for recombinant proteins.

PMID- 22960760
TI  - The cell walls of syncytia formed by Heterodera schachtii in Arabidopsis thaliana
      are abundant in methyl-esterified pectin.
AB  - Plant-parasitic cyst nematodes form a specialized feeding site, termed a
      syncytium, in the roots of host plants. Monoclonal antibodies to defined glycans,
      in addition to a cellulose-binding module, were used to characterize the cell
      walls of a functioning syncytia in situ. Cell walls of syncytia were found to
      contain cellulose, xyloglucan and mannan. Analysis of the pectin network revealed
      syncytial cell walls are abundant in homogalacturonan, which was heavily methyl
      esterified. Arabinan was also detected and the results suggest the cell walls of
      syncytia are highly flexible.

PMID- 22960762
TI  - Gender inequities pervade organ transplantation access.

PMID- 22960761
TI  - Post-transcriptional control of miRNA abundance in Arabidopsis.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs (small RNAs) that are 20
      24nt in length and predominantly repress gene expression at post-transcriptional
      levels. They regulate many biological processes including development, metabolism
      and physiology. Numerous studies have revealed that the steady-state levels of
      miRNA are under sophisticated control to ensure their proper function. In this
      review, we summarize recent advances on regulation of miRNA processing and
      stability in plants.

PMID- 22960763
TI  - Conversion from tacrolimus/mycophenolic acid to tacrolimus/leflunomide to treat
      cutaneous warts in a series of four pediatric renal allograft recipients.
AB  - BACKGROUND: The challenge of immunosuppression in pediatric renal transplantation
      is to balance preventing rejection while avoiding infectious complications. A
      dermatological complication of immunosuppression is viral warts, which cause
      significant disfigurement and increase the risk of skin malignancy. METHODS: We
      present three pediatric and adolescent renal allograft recipients with multiple,
      recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum
      who were switched from mycophenolate mofetil to leflunomide. Teriflunomide
      metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to
      balance its immunosuppressive and antiviral properties. No adverse events
      requiring discontinuation of leflunomide were encountered. RESULTS: Switching
      from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares
      and molluscum lesions in all four renal transplant patients. CONCLUSIONS: The
      ability to minimize and even resolve warts can improve quality of life by
      reducing risk of skin malignancies and emotional distress in solid organ
      transplant patients. Leflunomide is a potential therapeutic option for
      posttransplantation patients with skin warts because it serves both as an adjunct
      to the immunosuppressive regimen and an antiviral agent.

PMID- 22960764
TI  - Pharmacodynamic analysis of tofacitinib and basiliximab in kidney allograft
      recipients.
AB  - BACKGROUND: The common gamma-chain (gamma(c)) cytokines signal through the Janus
      kinase (JAK)-signal transducer and activator of transcription (STAT) pathway and
      play pivotal roles in lymphocyte activation. We investigated the effect of
      immunosuppressive drugs targeting this pathway, the JAK inhibitor tofacitinib (CP
      690,550) and the anti-interleukin (IL)-2R antibody basiliximab, as part of a
      phase 2 study. METHODS: After whole-blood activation with the gamma(c) cytokines
      IL-2, IL-7, and IL-15, STAT5 phosphorylation was determined in T cells of de novo
      kidney transplantation patients treated with tofacitinib/basiliximab (n=5),
      calcineurin inhibitor (CNI) (cyclosporine A)/basiliximab (n=4) or CNI
      (tacrolimus)-based immunosuppression (n=6). The IC(50) for phosphorylated STAT (P
      STAT) 5 inhibition by tofacitinib was determined in cytokine-activated CD4(+) and
      CD8(+) T cells from healthy individuals (n=4). RESULTS: IC(50) was 26, 72, and 37
      ng/mL for IL-2, IL-7, and IL-15 activation, in CD4(+) T cells, respectively; and
      35, 61, and 76 ng/mL for IL-2, IL-7, and IL-15 activation, in CD8(+) T cells,
      respectively. In kidney transplantation patients, 7 days after starting
      tofacitinib/basiliximab treatment, cytokine-induced P-STAT5 was inhibited in
      CD4(+) T cells (92% for IL-2 activation, 60% for IL-7, and 75% for IL-15), which
      persisted for the 2-month study period. In contrast, CNI/basiliximab treatment
      did not affect IL-7-activated or IL-15-activated P-STAT5; only IL-2-activated P
      STAT5 was reduced by 77% on day 7 and recovered to pretreatment levels within 2
      months. CD8(+) T cells showed a comparable profile to CD4(+) T cells. P-STAT5 was
      not inhibited in CNI-treated control patients. CONCLUSIONS: Tofacitinib therapy
      strongly inhibits gamma(c) cytokine-induced JAK/STAT5 activation, whereas
      basiliximab suppresses IL-2-stimulated activation only. Pharmacodynamic
      monitoring offers a unique tool to evaluate the biologic effects of
      immunosuppressive drugs.

PMID- 22960765
TI  - Inosine monophosphate dehydrogenase polymorphisms and renal allograft outcome.
AB  - BACKGROUND: Interindividual variation in inosine monophosphate dehydrogenase
      (IMPDH) enzyme activity and adverse effects caused by mycophenolate mofetil (MMF)
      inhibition may be genetically determined, and if so, transplant recipients should
      receive personalized dosing regimens of MMF, which would maximize efficacy and
      minimize toxicity. Some studies have demonstrated a relationship between the
      single nucleotide polymorphism and the risk of acute rejection with IMPDH I
      variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others
      have failed to exhibit an effect. The aim of this work was to investigate the
      influence of these polymorphisms on acute rejection rates, graft survival and
      function, and MMF doses in a large cohort of patients. METHODS: A random sample
      of 1040 recipients from the Collaborative Transplant Study DNA bank was genotyped
      for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052.
      RESULTS: The presence of the T (rs2278293) and G alleles (rs2278294) in the IMPDH
      I variants and carriage of the G allele (rs11706052) in the IMPDH II variant did
      not increase the risk of rejection or affect graft function by 1 year after
      transplantation. There was no association with MMF dose tolerated at 1 year.
      Furthermore, these polymorphisms did not impact graft or patient survival at 5
      years. CONCLUSION: This study represents the largest cohort of patients with the
      longest follow-up to date and does not support previous evidence for an
      association between these IMPDH variants and renal allograft rejection and graft
      survival.

PMID- 22960766
TI  - Antiviral protection against enterovirus 71 mediated by autophagy induction
      following FLICE-inhibitory protein inactivation.
AB  - Even with the recent awareness of enterovirus 71 (EV71) as a major public health
      issue, there are no preventive or therapeutic agents that are effective against
      EV71 infection. Although FLICE-like inhibitory protein (FLIP) has been identified
      as a factor that modulates virus pathogenesis, there are no reports regarding its
      effects on EV71 infection. The aim of the present study was to identify whether
      FLIP influences EV71 pathogenesis and to understand the underlying mechanisms.
      Virus replication was markedly reduced in MRC5 cells preincubated with anti-FLIP
      peptides, and infected cells were rescued from the cytopathic effects of the
      virus. The anti-FLIP peptides induced autophagy by disrupting intrinsic FLIP
      functions. The antiviral activity of these peptides was reduced when autophagy
      was inhibited by treatment with siRNA targeted to beclin-1. Thus, the present
      study provides evidence that anti-FLIP peptides induce autophagy by inactivating
      cFLIP, and that this is associated with antiviral effects against EV71.

PMID- 22960767
TI  - Need for episiotomy in a subsequent delivery following previous delivery with
      episiotomy.
AB  - PURPOSE: To assess the need of episiotomy in a subsequent delivery in women with
      previous primiparous vaginal delivery with episiotomy. METHODS: In this
      historical prospective study, we followed primiparous women who had an episiotomy
      at a normal vaginal delivery. The study group included parturient women (n = 201)
      who underwent an episiotomy at a vaginal delivery during a 2-year period (2001
      2002). Inclusion criteria were: primiparity, term singleton vaginal delivery,
      episiotomy, and a subsequent vaginal delivery in Edith Wolfson Medical Center.
      Exclusion criteria were instrumental delivery at the index delivery, preterm
      delivery or twins at the subsequent delivery. Episiotomy in the enrolled
      parturient women was done when it is thought that failure to perform episiotomy
      would result in perineal tears. The control group (n = 201) was formed from the
      same time period and included women who had a spontaneous vaginal delivery
      without episiotomy. RESULTS: Of the 201 women with episiotomy at the index
      delivery, 48 (23.9 %) had episiotomy at the subsequent delivery compared to only
      20 women (10.0 %) out of the 201 women without an episiotomy at index delivery (p
      < 0.05). Having an episiotomy at the index delivery significantly increased odds
      of a subsequent episiotomy (OR 2.84, 95 % CI 1.62-4.99, p < 0.05) and the risk of
      spontaneous perineal tears (59.2 vs. 23.4 %, p < 0.05) at the subsequent
      delivery. CONCLUSION: Episiotomy at first vaginal delivery significantly and
      independently increased the risk of repeated episiotomy and spontaneous perineal
      tears in a subsequent delivery.

PMID- 22960768
TI  - Ink4-Arf locus in cancer and aging.
AB  - Three tumor suppressor genes at the small (<50 kb) INK4-ARF (CDKN2A/B) locus on
      human chromosome 9p21 coordinate a signaling network that depends on the
      activities of the retinoblastoma (RB) protein and the p53 transcription factor.
      Disruption of this circuitry, frequently by codeletion of INK4-ARF, is a hallmark
      of cancer, begging the question of why the intimate genetic linkage of these
      tumor suppressor genes has been maintained in mammals despite the risk of their
      coinactivation. The INK4-ARF locus is not highly expressed under normal
      physiologic conditions in young mammals, but its induction becomes more
      pronounced as animals age. Notably, INK4-ARF is actively silenced en bloc in
      embryonic, fetal, and adult stem cells but becomes poised to respond to oncogenic
      stress signals as stem cells lose their self-renewal capacity and differentiate,
      thereby providing a potent barrier to tumor formation. Epigenetic remodeling of
      the locus as a whole provides a mechanism for coordinating the activities of RB
      and p53. A hypothesis is that the INK4-ARF locus may have evolved to
      physiologically restrict the self-renewal capacities and numbers of stem and
      progenitor cells with the attendant consequence of limiting tissue regenerative
      capacity, particularly as animals age. Deletion of INK4-ARF contributes to the
      aberrant self-renewal capacity of tumor cells and occurs frequently in many forms
      of human cancer.

PMID- 22960770
TI  - Appearance concern and depression in adolescent girls with systemic lupus
      erythematous.
AB  - To examine the relationship between physical appearance concern and psychological
      distress in female adolescent patients with systemic lupus erythematosus (SLE)
      was the aim of this study. A total of 84 adolescent SLE female patients and 80
      age-matching healthy adolescents were evaluated for levels of appearance concern
      and a range of illness-specific measures to determine how these demographic and
      clinical variables were related to the dependent variable psychological distress.
      The Systemic Lupus Erythematosus Disease Activity Index was used to assess
      disease activity. Assessment of depression was conducted through the children
      depression inventory (CDI). Appearance concern was measured using the Self
      Perception Profile for Children. The total CDI was 18.5 +/- 4.3, indicating that
      these patients had more depressive symptoms, comparing with age- and sex-matched
      healthy controls. Furthermore, a total of 32 (38.1 %) patients had CDI larger
      than 19 points, indicating that they have relatively higher risk in developing
      depression. The CDI in control group was significantly lower than that in the SLE
      group (11.4 +/- 1.7 vs. 18.5 +/- 4.3, t = 9.93, p < 0.05). Using correlation and
      multiple regression analyses, we found that both appearance concern and age were
      predictive of depression in patients with SLE, and the former was highly
      correlated. This indicates that appearance concern may be associated with
      depression in female adolescent SLE patients. The results suggest that appearance
      concern is strongly associated with depression in female adolescent patients with
      SLE and should be routinely assessed.

PMID- 22960769
TI  - Early initiation of gonadotropin-releasing hormone antagonist in polycystic
      ovarian syndrome patients undergoing assisted reproduction: randomized controlled
      trial ISRCTN69937179.
AB  - PURPOSE: To compare the implantation rates in two groups of women with Polycystic
      Ovary Syndrome (PCOS) after embryo transfer based on the initiation time of GnRH
      antagonist. Secondary outcome measures included clinical pregnancy, delivery and
      miscarriage rates. METHODS: This is a prospective, randomized trial in which 140
      PCOS patients underwent ICSI, with 122 having ET performed. GnRH-antagonist was
      started on day 1 of stimulation in 69 patients (Group 1) or day 5 in 71 patients
      (Group 2). RESULTS: The overall implantation rate in Group 1 (46.2 %) was
      clinically higher than Group 2 (35.5 %), although not statistically significant
      (p = 0.075). For blastocysts transfer, the implantation rate in Group 1 was 55.1
      %, compared to 40.4 % in Group 2 (p = 0.051). There was a clinically, but not
      statistically, higher clinical pregnancy rate (68.3 % vs. 56.5 %) and delivery
      rate (60.0 % vs. 53.2 %) per transfer in Group 1 compared to Group 2,
      respectively. There was a statistically significant lower biochemical pregnancy
      rate in Group 1 (2.4 %) compared to Group 2 (18.6 %) [p = 0.015]. There was no
      difference in miscarriage rates between the two groups. CONCLUSION: Our data
      suggest that early initiation of GnRH antagonist on day 1 of ovarian stimulation
      in PCOS patients undergoing ICSI-ET may improve implantation rates, especially
      after blastocyst transfer.

PMID- 22960771
TI  - Carotid enlargement and serum levels of von Willebrand factor in rheumatoid
      arthritis: a follow-up study.
AB  - This follow-up study aimed to evaluate the relationship between serum levels of
      von Willebrand factor (vWf) and common carotid intima-media thickness (IMT) in
      patients with rheumatoid arthritis (RA). In the initial assessment, 34 female
      rheumatoid arthritis patients and 30 sex- and age-matched controls were included.
      The relationship among vWf serum levels, cardiovascular risk factors, and
      inflammation was initially assessed. The effects of these variables on carotid
      IMT were evaluated 5 years later. There were no significant differences between
      the RA patients and the controls in terms of IMT at the first evaluation. Five
      years later, the carotid IMT increased more significantly in RA patients if
      compared to controls (p < 0.001). The progression of carotid IMT significantly
      correlated with erythrocyte sedimentation rate (ESR) (r = 0.368, p = 0.032) and C
      reactive protein (r = 0.506, p = 0.002). The progression of carotid IMT did not
      significantly correlate with vWf serum levels in the RA patients, although, at
      initial and repeated measurements, it showed statistically higher values of vWF
      in the RA patients compared to the control group (p < 0.01). The RA patients
      displayed accelerated development of atherosclerosis, as indicated by the
      increased IMT of carotid artery. Increased serum levels of vWF may suggest its
      potential role in cardiovascular risk prediction in RA patients.

PMID- 22960772
TI  - Engineering of polarized tubular structures in a microfluidic device to study
      calcium phosphate stone formation.
AB  - This communication describes the formation of tubular structures with a circular
      cross-section by growing epithelial cells in a microfluidic (MF) device. Here we
      show for the first time that it is possible to form a monolayer of polarized
      cells, embedded within the MF device which can function as an in vivo epithelia.
      We showed: i) the overexpression of specific protein(s) of interest (i.e., ion
      channel and transport proteins) is feasible inside tubular structures in MFs; ii)
      the functional kinetic information of Ca(2+) in cells can be measured by
      microflurometry using cell permeable Ca(2+) probe under confocal microscope; and
      iii) calcium phosphate stones can be produced in real time in MFs with Ca(2+)
      transporting epithelia. These data suggest that tubular structures inside this MF
      platform can be used as a suitable model to understand the molecular and
      pharmacological basis of calcium phosphate stone formation in the epithelial or
      other similar cellular micro environments.

PMID- 22960773
TI  - Differential influence of morphine sensitization on accumbens shell and core
      dopamine responses to morphine- and food-conditioned stimuli.
AB  - RATIONALE: Sensitization of the incentive and dopamine (DA) stimulant properties
      of drug-conditioned stimuli (CSs) by repeated exposure to drugs of abuse has been
      assigned an important role in the genesis of drug addiction. OBJECTIVE: To test
      in rats if morphine-induced sensitization potentiates incentive and DA-releasing
      properties in the nucleus accumbens (NAc) shell and core elicited by presentation
      of a morphine-conditioned stimulus(CS) and if this property generalizes to a non
      drug-(palatable food, Fonzies)-CS. METHODS: Controls and rats previously
      sensitized by morphine were trained via three daily sessions consisting of a 10
      min presentation of CS (Fonzies filled box, FB) followed by s.c. saline and
      morphine (1 mg/kg) or by standard food and Fonzies. Rats were implanted with
      microdialysis probes and the next-day incentive reactions and NAc shell and core
      DA were monitored during CS presentation and subsequent morphine (1 mg/kg)
      administration or Fonzies feeding. RESULTS: Morphine sensitization increased
      incentive and NAc shell and core DA responses to morphine-CS. Morphine
      conditioning per se increased incentive reactions and NAc shell but not core DA
      responses to FB presentation. Morphine sensitization potentiated incentive
      responses but did not affect NAc shell and core DA responses to Fonzies-CS.
      Fonzies conditioning increased incentive reactions and NAc core but not shell DA
      responses to FB presentation. CONCLUSIONS: These observations confirm the
      prediction of the incentive sensitization theory in the case of drug-CS but not
      of non-drug-CS. NAc DA might be differentially involved in the expression of
      incentive sensitization of drug- and non-drug-CSs, thus providing a clue for the
      abnormal incentive properties of drug CSs.

PMID- 22960775
TI  - Morphometry of typical cervical vertebrae on dry bones and CT scan and its
      implications in transpedicular screw placement surgery.
AB  - BACKGROUND: Transpedicular stabilization of subaxial cervical spine is a very
      delicate procedure that requires thorough understanding of the pedicle anatomy to
      minimize the rate of neurovascular complications. The current study was conducted
      to investigate the morphometric details including dimensions and axis of typical
      cervical vertebrae (C3-C6) for transpedicular screw insertion surgery. METHODS:
      The current study was conducted on 100 sides of 50 dry and 160 sides of 80
      vertebrae on computerized tomography scans of typical cervical vertebrae.
      Parameters that were studied bilaterally included distance between medial aspect
      of the pedicle and dural sac, pedicle height, pedicle width, interpedicular
      distance, lateral and medial cortical thickness, transverse pedicle angle and
      chord length. RESULTS: Distance between medial aspect of the pedicle and dural
      sac was found to be 2.2 +/- 0.99 mm. Mean pedicle height (6.5 +/- 1.1 mm) was
      found to be greater than pedicle width (4.9 +/- 0.9 mm) in all the vertebrae.
      Mean transverse pedicle angle and chord length was observed to be 39.4 degrees 
      and 32.1 mm, respectively. Mean interpedicular distance, medial and lateral
      cortical thickness was observed to be 21.8 +/- 1.6, 1.43 +/- 0.4 and 0.79 +/- 0.2
      mm, respectively. CONCLUSIONS: The present study highlights a three-dimensional
      orientation of subaxial cervical pedicle anatomy, while emphasizing the risks
      involved in the view of comparatively smaller values of pedicle dimensions of
      subaxial cervical vertebrae. This knowledge about typical cervical vertebrae, its
      pedicle and their adjacent neurovascular structures may enhance the safety of
      transpedicular screw insertion.

PMID- 22960774
TI  - Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned
      helplessness paradigm.
AB  - RATIONALE: Stress is a common antecedent reported by people suffering major
      depression. In these patients, extrahypothalamic brain areas, like the
      hippocampus and basolateral amygdala (BLA), have been found to be affected. The
      BLA synthesizes CRF, a mediator of the stress response, and projects to
      hippocampus. The main hippocampal target for this peptide is the CRF subtype 1
      receptor (CRF1). Evidence points to a relationship between dysregulation of
      CRF/CRF1 extrahypothalamic signaling and depression. OBJECTIVE: Because selective
      serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological
      treatment for depression, we investigated the effect of chronic treatment with
      the SSRI fluoxetine on long-term changes in CRF/CRF1 signaling in animals showing
      a depressive-like behavior. METHODS: Male Wistar rats were exposed to the learned
      helplessness paradigm (LH). After evaluation of behavioral impairment, the
      animals were treated with fluoxetine (10 mg/kg i.p.) or saline for 21 days. We
      measured BLA CRF expression with RT-PCR and CRF1 expression in CA3 and the
      dentate gyrus of the hippocampus with in situ hybridization. We also studied the
      activation of one of CRF1's major intracellular signaling targets, the
      extracellular signal-related kinases 1 and 2 (ERK1/2) in CA3. RESULTS: In saline
      treated LH animals, CRF expression in the BLA increased, while hippocampal CRF1
      expression and ERK1/2 activation decreased. Treatment with fluoxetine reversed
      the changes in CRF and CRF1 expressions, but not in ERK1/2 activation.
      CONCLUSION: In animals exposed to the learned helplessness paradigm, there are
      long-term changes in CRF and CRF1 expression that are restored with a
      behaviorally effective antidepressant treatment.

PMID- 22960776
TI  - Radiological landmarks for the safe extra-capsular placement of supra-acetabular
      half pins for external fixation.
AB  - PURPOSE: Low anterior external fixators are constructed by placing half pins in
      the dense bone tunnel of the supra-acetabular region in an anterior to posterior
      direction. Although the placement of these pins is extra-articular, they may
      still breach the hip capsule on the anterior inferior iliac spine and thus be
      intra-capsular. We aim to provide radiological markers for the most superior
      fibres of the capsule to allow safe extra-capsular pin placement within the supra
      acetabular bone tunnel. METHODS: Thirteen cadaveric pelves were used for this
      study. The supra-acetabular bone tunnel was visualised with an image intensifier.
      The proximal most fibres of the hip joint capsule were marked with a K-wire so
      that their relation to the bone tunnel could be clearly seen on the images. Once
      all images were acquired they were calibrated and analysed to estimate the
      dimensions of the supra-acetabular bone tunnel and the reflection of the hip
      capsule. RESULTS: The median height of the bone tunnel was 23.6 mm (18.9-33.2)
      and maximum width was 11.4 mm (7.6-16.3). The inferior margin of the bone tunnel
      was 6.7 mm (1.1-14.5) superior to the acetabular dome, and the most proximal
      fibres of the capsule were 9.3 mm (4.7-6.1) superior to the acetabular dome. The
      inferior portion of the tunnel was 3.7 mm (0.3-8.9) within the joint. CONCLUSION:
      Half pins for the construction of a pelvic external fixator should be placed in
      the upper half of the supra-acetabular bone corridor to minimise the risk of
      intra-capsular placement.

PMID- 22960777
TI  - Second primary cancers after cancer of unknown primary in Sweden and Germany:
      efficacy of the modern work-up.
AB  - In unsparing efforts to find the hidden primaries, second primary cancers (SPCs)
      unrelated to cancer of unknown primary (CUP) are found. The detection rates of
      SPCs after CUP can be considered as measures for the effectiveness of modern
      diagnostic techniques in finding tumors. We aimed to compare the rates of
      specific SPCs found after the work-up of CUP and the more sign/symptom-directed
      diagnostic approaches applied after any other cancer. The number of CUP patients
      identified in the nationwide Swedish database and nine German cancer registries
      was 24 641 from 1997 through 2006, and rate ratios (RRs) for SPCs were recorded
      in two follow-up periods. The detection rate of SPCs immediately after any other
      cancer was about two times higher in Germany than in Sweden, but the rate
      immediately after CUP was almost the same for the two datasets. In the joint
      analyses after CUP, the RRs of liver, lung, breast, and kidney cancers were
      higher than after any other cancer, whereas the RRs of prostate, urinary bladder,
      and connective tissue cancers as well as non-Hodgkin's lymphoma were not
      significantly different; the RR of cancers of upper aerodigestive tract was lower
      after CUP than after any other cancer. The joint data indicate that the work-up
      is efficient in detecting tumors in the thoracoabdominal organs that are screened
      by computed tomography. For some other organ sites, the more sign/symptom
      directed diagnostic approaches may be equally efficient. However, none of the
      applied techniques could detect all tumors immediately after the first diagnosis.

PMID- 22960778
TI  - Risk factors for sporadic medullary thyroid carcinoma.
AB  - Medullary thyroid cancer is a rare tumour that appears in two distinct forms. The
      rarer familial form is genetically determined. The sporadic form is more common,
      but its aetiology has not been defined clearly so far. The aim of this study was
      to examine the risk factors for development of sporadic medullary thyroid cancer
      (sMTC). A case-control study was carried out during the period 2000-2009. The
      case group included 98 consecutive patients with sMTC. The control group
      comprised twice as many cases (196), who were neighbours of the patients from the
      case group. Patients were individually matched by sex, age and place of
      residence. Conditional univariate and multivariate logistic regression methods
      were applied in data analyses. According to the univariate logistic regression
      method, sMTC was significantly related to smoking status, duration of smoking,
      number of cigarettes smoked per day, personal history of goitre or thyroid
      nodules, personal history of nonthyroid cancer, menarche after 14 years of age,
      first full-term pregnancy before 20 years of age and usage of oral
      contraceptives. According to the multivariate logistic regression method, sMTC
      was independently related to smoking status [odds ratio (OR)=0.46, 95% confidence
      interval (CI)=0.20-0.90], personal history of goitre or thyroid nodules
      (OR=11.29, 95% CI=1.16-73.45) and menarche after 14 years of age (OR=2.77, 95%
      CI=1.33-6.28). Risk factors for sMTC were goitre or thyroid nodules and late
      menarche; cigarette smoking appeared to be a protective factor.

PMID- 22960779
TI  - Cleaning contaminated environment: a growing challenge.

PMID- 22960780
TI  - [Haemophilia treatment centres in Germany].
AB  - An adequate number of qualified haemophilia centres is an essential requirement
      for effective and cost-efficient haemophilia care. During a reassessment of the
      delivery of haemophilia care in Germany a broad range of criteria relating to
      structure and quality of the centres were defined and a questionnaire was
      developed. RESULTS: Of 137 doctors who received the questionnaire, 113 (82%)
      replied. Based on data related to diagnostic and treatment services, together
      with voluntary information from PEI forms (Paul Ehrlich Institut, Germany), 72
      haemophilia centres were established. Three levels of haemophilia care were
      defined by the Medical Advisory Council of the German Haemophilia Society. This
      is in accordance with criteria defined by European working parties. 17
      haemophilia centres were designated CCC (Comprehensive Care Centre), 24 were
      designated HTC (Haemophilia Treatment Centre) and 31 smallest centres were
      allocated the status HTR (Haemophilia Treatment Regional). In comparison to the
      survey in 2007, there was only slight variance in the CCC centres (+ 2 centres/-1
      centre). From the previous HTC centres, 7 have withdrawn from this treatment
      level: 4 maintain treatment on the lower level HTR, and 3 centres had ceased
      treatment. On the HTR level of treatment, 6 of 29 (21%) had ceased to offer
      treatment. 9 had been able to increase the number of patients and were designated
      HTC. 5404 patients with haemophilia and 3047 with the severe form of haemophilia
      were reported. 67% were treated in CCC, 25% in haemophilia treatment centres and
      8% in the 31 smallest centres. 13 of the adult CCC are situated in the department
      of internal medicine and 4 in the section of transfusion medicine. CONCLUSIONS:
      The survey and analysis of the haemophilia treatment centres in Germany show that
      the delivery of haemophilia care through 17 CCC, 24 HCT and 31 HTR appears to be
      adequately structured. But it is noticeable and alarming, however, that on both
      HTC and HTR levels of treatment, 32% and 21%, respectively, have left their
      treatment level. 9 centres (12.5%) have finished working in haemophilia care in
      the last four years. On the strength of these results, endeavours to maintain
      haemophilia centres must be intensified. A high level of effective care can be
      guaranteed only through continued existence of the centres.

PMID- 22960781
TI  - An in vivo zebrafish screen identifies organophosphate antidotes with diverse
      mechanisms of action.
AB  - Organophosphates are a class of highly toxic chemicals that includes many
      pesticides and chemical weapons. Exposure to organophosphates, either through
      accidents or acts of terrorism, poses a significant risk to human health and
      safety. Existing antidotes, in use for over 50 years, have modest efficacy and
      undesirable toxicities. Therefore, discovering new organophosphate antidotes is a
      high priority. Early life stage zebrafish exposed to organophosphates exhibit
      several phenotypes that parallel the human response to organophosphates,
      including behavioral deficits, paralysis, and eventual death. Here, we have
      developed a high-throughput zebrafish screen in a 96-well plate format to find
      new antidotes that counteract organophosphate-induced lethality. In a pilot
      screen of 1200 known drugs, we identified 16 compounds that suppress
      organophosphate toxicity in zebrafish. Several in vitro assays coupled with
      liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled
      determination of mechanisms of action for several of the antidotes, including
      reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and
      inhibition of bioactivation. Therefore, the in vivo screen is capable of
      discovering organophosphate antidotes that intervene in distinct pathways. These
      findings suggest that zebrafish screens might be a broadly applicable approach
      for discovering compounds that counteract the toxic effects of accidental or
      malicious poisonous exposures.

PMID- 22960782
TI  - Validation of a high-throughput, automated electrophysiology platform for the
      screening of nicotinic agonists and antagonists.
AB  - High-throughput compound screening using electrophysiology-based assays
      represents an important tool for biomedical research and drug discovery programs.
      The recent development and availability of devices capable of performing high
      throughput electrophysiology-based screening have brought the need to validate
      these tools by producing data that are consistent with results obtained with
      conventional electrophysiological methods. In this study, we compared the
      response properties of halpha3beta4 and halpha4beta2 nicotinic receptors to their
      endogenous ligand acetylcholine (ACh) using three separate electrophysiology
      platforms: Dynaflow (low-throughput, manual system), PatchXpress 7000A (medium
      throughput automated platform), and IonWorks Barracuda (high-throughput automated
      platform). We found that despite the differences in methodological approaches
      between these technologies, the EC(50) values from the ACh dose-response curves
      were consistent between all three platforms. In addition, we have validated the
      IonWorks Barracuda for both competitive and uncompetitive inhibition assays by
      using the competitive nicotinic antagonist dihydro-beta-erythroidin (DHbetaE) and
      uncompetitive nicotinic antagonist mecamylamine. Furthermore, we have
      demonstrated the utility of a custom-written algorithm for generating dose
      response curves from multiple extrapolated current metrics that allows for
      discriminating between competitive and uncompetitive inhibition while maintaining
      high-throughput capacity. This study provides validation of the consistency of
      results using low-, medium-, and high-throughput electrophysiology platforms and
      supports their use for screening nicotinic compounds.

PMID- 22960783
TI  - A 12-week exercise therapy program in middle-aged patients with degenerative
      meniscus tears: a case series with 1-year follow-up.
AB  - STUDY DESIGN: Case series. BACKGROUND: Exercise is a viable treatment alternative
      to arthroscopic partial meniscectomy in patients with degenerative meniscus
      tears. No study has reported in detail the type of exercises, progression,
      tolerance, and potential benefit from an exercise therapy program in these
      patients who have not had surgery. This case report describes a progressive
      exercise therapy program aimed at improving neuromuscular function and muscle
      strength in middle-aged patients with degenerative meniscus tears, the outcome
      over a 12-week period, and the ability to maintain improvements up to 1 year.
      CASE DESCRIPTION: The first 20 patients (age range, 38-58 years) included in an
      ongoing randomized controlled trial. OUTCOMES: Outcomes data included the Knee
      injury and Osteoarthritis Outcome Score, a 7-point global rating of change scale,
      isokinetic knee muscle strength tests, and 3 lower extremity performance tests.
      Postintervention, 16 of 20 patients showed clinically meaningful changes (greater
      than 10 points) on the Knee injury and Osteoarthritis Outcome Score knee-related
      quality of life subscale, 19 of 20 patients rated themselves as "a lot better" or
      "better" on the global rating of change scale, all patients had increased
      quadriceps muscle strength, and the majority of patients improved on the lower
      extremity performance tests. At 1 year postintervention, the majority of patients
      had maintained the improvements and none of the patients had undergone surgery.
      DISCUSSION: The described neuromuscular- and strength-training program should be
      considered for rehabilitation of middle-aged individuals with degenerative
      meniscus tears. However, head-to-head comparison of programs in a randomized
      design is needed to determine if this specific program is significantly better
      than other interventions.

PMID- 22960784
TI  - Structural, spectroscopic and redox properties of a mononuclear Co(II) thiolate
      complex--the reactivity toward S-alkylation: an experimental and theoretical
      study.
AB  - The structural, spectroscopic, redox properties and also the reactivity toward S
      alkylation of a new mononuclear N2S2 dithiolate Co(II) complex [CoL] (1), with
      H(2)L = 2,2'-(2,2'-bipyridine-6,6'-diyl)bis(1,1-diphenylethanethiol), have been
      investigated. The X-ray structure of 1 has revealed an unusual distorted square
      planar geometry for a Co(II) ion within a thiolate environment. The X-band EPR
      spectrum of displays a rhombic S = 1/2 signal consistent with a low spin
      configuration for the d(7) Co(II) ion with a large g-anisotropy (g(x) = 2.94,
      g(y) = 2.32 and g(z) = 2.01). By pulsed EPR experiments (HYSCORE), two weak
      hyperfine couplings (hfc) of 3.2 and 2.2 MHz have been measured and attributed
      respectively to protons and nitrogen nuclei of the bipyridine unit. In addition,
      another hyperfine coupling (hfc) of 7.5 MHz has been attributed to the cobalt
      ion. DFT calculations have successfully reproduced the (59)Co and (14)N hfc
      parameters. However, multiconfigurational ab initio calculations were required to
      predict the g-tensor of 1. The cyclic voltammogram (CV) displays two one-electron
      metal based processes: a quasi-reversible Co(III)/Co(II) oxidation wave at E(1/2)
      = -0.5 V vs. Fc(+)/Fc and a quasi-reversible Co(II)/Co(I) reduction wave at
      E(1/2) = -1.7 V. 1 reacts with CH(3)I, generating the mono S-methylated complex,
      [CoL(Me)I] (1(Me)). The X-band EPR spectrum of 1(Me) displays a typical signal of
      a high spin (S = 3/2) Co(II) species. An optimized structure of 1(Me), calculated
      by DFT, is consistent with its EPR and UV-visible spectra. Time dependent density
      functional theory (TD-DFT) calculations attribute the most prominent features
      observed in the electronic absorption spectra of 1 and 1(Me). The singly occupied
      MO (SOMO) of 1 shows a notable delocalization of the unpaired electron over the
      metal (85%) and the ligand, especially over the sulphur atoms (10.5%), indicating
      a certain degree of covalency for the Co-S bonds. In 1(Me), for two of the three
      SOMOs, the unpaired electron is notably delocalized over the metal (78.5 and
      77.6%, respectively) and the ligand (12.5 and 7.8%, respectively over the sulphur
      of the thiolate function). For the third SOMO, the unpaired electron is mainly
      localized on the metal (92.2%). There is no electronic density spread on the
      sulphur atom of the thioether function in any of these SOMOs. The reactivity and
      the electronic properties of 1 are also compared with those of the analogous
      [ZnL] and [NiL] complexes.

PMID- 22960786
TI  - Partial therapeutic response to Rituximab for the treatment of chronic
      alloantibody mediated rejection of kidney allografts.
AB  - BACKGROUND AND OBJECTIVES: Chronic rejection leads to kidney allograft failure
      and develops in many kidney transplant recipients. One cause of chronic
      rejection, chronic antibody mediated rejection (CAMR), is attributed to
      alloantibodies. Maintenance immunosuppression including prednisone, mycophenolate
      mofetil (MMF) and calcineurin inhibitors may limit alloantibody production in
      some patients, but many maintain or develop alloantibody production, leading to
      CAMR. Therefore, no efficacious therapy to treat CAMR is presently available to
      prevent the progression of CAMR to kidney allograft failure. DESIGN, SETTING,
      PARTICIPANTS, AND MEASUREMENTS: We performed a retrospective review of 31
      subjects with CAMR, of which 14 received Rituximab and 17 subjects did not.
      Response to Rituximab was defined as decline or stabilization of serum creatinine
      for at least one year. Data reviewed included demographic, clinical, allograft,
      post-transplant, and pathological variables. Pathological variables in the
      diagnostic allograft biopsy were scored according to Banff criteria. RESULTS: The
      median survival time (MST) for allografts in the control group was 439 days, and
      for the Rituximab treated group was 685 days. The Rituximab group was dichotomous
      with 8 subjects showing a medial survival time of 1180 days, and 6 subjects
      having a median survival time of 431 days. The MST for the responders was
      statistically significant from the non-responders and controls. No pathological
      parameter distinguished any subset of subjects. CONCLUSIONS: These data show that
      Rituximab followed by standard maintenance immunosuppression shows a therapeutic
      effect in the treatment of CAMR, which is confined to a subset of treated
      subjects, not identifiable a priori.

PMID- 22960787
TI  - Devices for overcoming biological barriers: the use of physical forces to disrupt
      the barriers.
AB  - Overcoming biological barriers including skin, mucosal membranes, blood brain
      barrier as well as cell and nuclear membrane constitutes a key hurdle in the
      field of drug delivery. While these barriers serve the natural protective
      function in the body, they limit delivery of drugs into the body. A variety of
      methods have been developed to overcome these barriers including formulations,
      targeting peptides and device-based technologies. This review focuses on the use
      of physical methods including acoustic devices, electric devices, high-pressure
      devices, microneedles and optical devices for disrupting various barriers in the
      body including skin and other membranes. A summary of the working principles of
      these devices and their ability to enhance drug delivery is presented.

PMID- 22960789
TI  - Functional impact of interneuronal inhibition in the cerebral cortex of behaving
      animals.
AB  - This paper reviews recent progress in understanding the functional roles of
      inhibitory interneurons in behaving animals and how they affect information
      processing in cortical microcircuits. Multiple studies have shown that the
      morphological subtypes of inhibitory cells show distinct electrophysiological
      properties, as well as different molecular and neurochemical identities,
      providing a large mosaic of inhibitory mechanisms for the dynamic processing of
      information in the cortex. However, it is only recently that some specific
      functions of different interneuronal subtypes have been described in behaving
      animals. In this regard, influential results have been obtained using the known
      differences of interneurons and pyramidal cells recorded extracellularly to
      dissociate the functional roles that these two classes of neurons may play in the
      cortical microcircuits during various behaviors. Neurons can be segregated into
      fast-spiking (FS) cells that show short action potentials, high discharge rates,
      and correspond to putative interneurons; and regular-spiking (RS) cells that show
      larger action potentials and correspond to pyramidal neurons. Using this
      classification strategy, it has been found that cortical inhibition is involved
      in sculpting the tuning to different stimulus or behavioral features across a
      wide variety of sensory, association, and motor areas. Recent studies have
      suggested that the increase in high-frequency synchronization during information
      processing and spatial attention may be mediated by FS activation. Finally, FS
      are active during motor planning and movement execution in different motor areas,
      supporting the notion that inhibitory interneurons are involved in shaping the
      motor command but not in gating the cortical output.

PMID- 22960790
TI  - Hypoxia-regulated neurotrophin-3 expression by multicopy hypoxia response
      elements reduces apoptosis in PC12 cells.
AB  - We have previously reported that 5 copies of the hypoxia response element (HRE)
      can conditionally regulate brain-derived neurotrophic factor gene expression
      under hypoxic/ischemic conditions in mice. In the present study, we investigated
      the controlled expression of neurotrophin-3 (NT-3) by HRE under hypoxic
      conditions and determined the protective effects of conditionally expressed NT-3
      on hypoxia-induced apoptosis in PC12 cells. Five copies of the HRE (5HRE) and the
      simian virus 40 minimal promoter (SV40mp) were employed to construct a cassette,
      and transfer of therapeutic gene, NT-3, into PC12 cells was achieved using a
      retroviral vector. Our results showed that the retroviral vector, pLNC-5HRE-NT3,
      was successfully constructed and transfected into PC12 cells. Compared with
      normal conditions, in which NT-3 was expressed at low levels, the expression of
      NT-3 significantly increased under hypoxic conditions in 5HRE-NT3 transgenic PC12
      cells (P<0.05). By contrast, in NT-3 transgenic PC12 cells without HRE, we found
      no significant difference in NT-3 expression between the normoxic and hypoxic
      groups. The conditional adjustment of NT-3 expression by 5HRE significantly
      reduced apoptosis induced by hypoxia in 5HRE-NT3 transgenic PC12 cells (P<0.05)
      but not in 5HRE-enhanced green fluorescent protein (EGFP) transgenic PC12 cells
      and PC12 cells without gene transfer. In addition, the hypoxia-induced
      upregulation of both p38 and caspase-3 activities was suppressed in 5HRE-NT3
      transgenic PC12 cells under hypoxic conditions (P<0.05). Taken together, these
      results demonstrate that 5HRE-SV40mp regulates NT-3 gene expression in response
      to hypoxia in PC12 cells. The data presented in this study may prove useful in
      future gene therapy studies for the treatment of ischemic diseases.

PMID- 22960791
TI  - [Risk pregnancies and how to treat them].
AB  - Recurrent abortions are a common problem. A therapy with low-molecular- weight
      heparin is usual in deep vein thrombosis with thrombophilia, in woman with
      recurrent abortions or other risks, like EPH-gestosis or HELLP-Syndrom. PATIENTS,
      METHOD: The efficacy of a mono-therapy with LMWH (3000-16000 daily) in women with
      risk pregnancies has been examined prospectively. The dates of 676 pregnant women
      have been analysed and compared to the current literature about live birth rates
      without therapy and tot he results of other, similar studies. The live birth rate
      has been the target variable. RESULTS: We obtained main a live birth rate of
      98.6%. There has been no record of serious adverse effects. We obtained a live
      birth rate of 95.8% if NMH therapy starts early, and a live birth rate of 100% if
      NMH therapy starts between week 20 and 25. For the live birth rate the existence
      of thrombophilic gene polymorphisms is irrelevant. CONCLUSION: The high live
      birth weight is depended on early starting the therapy with NMH. For the late
      risk it is favourable to start the therapy with heparin between week 20 and 25
      week of pregnancy.

PMID- 22960788
TI  - Induced pluripotent stem cells for cardiac repair.
AB  - Myocardial stem cell therapies are emerging as novel therapeutic paradigms for
      myocardial repair, but are hampered by the lack of sources for autologous human
      cardiomyocytes. An exciting development in the field of cardiovascular
      regenerative medicine is the ability to reprogram adult somatic cells into
      pluripotent stem cell lines (induced pluripotent stem cells, iPSCs) and to coax
      their differentiation into functional cardiomyocytes. This technology holds great
      promise for the emerging disciplines of personalized and regenerative medicine,
      because of the ability to derive patient-specific iPSCs that could potentially
      elude the immune system. The current review describes the latest techniques of
      generating iPSCs as well as the methods used to direct their differentiation
      towards the cardiac lineage. We then detail the unique potential as well as the
      possible hurdles on the road to clinical utilizing of the iPSCs derived
      cardiomyocytes in the emerging field of cardiovascular regenerative medicine.

PMID- 22960785
TI  - Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env
      V2.
AB  - The RV144 trial demonstrated 31% vaccine efficacy at preventing human
      immunodeficiency virus (HIV)-1 infection. Antibodies against the HIV-1 envelope
      variable loops 1 and 2 (Env V1 and V2) correlated inversely with infection risk.
      We proposed that vaccine-induced immune responses against V1/V2 would have a
      selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936
      HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined.
      We show that vaccine-induced immune responses were associated with two signatures
      in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses
      matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P =
      0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at
      position 181 was 78% (confidence interval 35% to 93%; P = 0.0028). Residue 169 is
      in a cationic glycosylated region recognized by broadly neutralizing and RV144
      derived antibodies. The predicted distance between the two signature sites (21 +/
      7 A) and their match/mismatch dichotomy indicate that multiple factors may be
      involved in the protection observed in RV144. Genetic signatures of RV144
      vaccination in V2 complement the finding of an association between high V1/V2
      binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence
      that vaccine-induced V2 responses plausibly had a role in the partial protection
      conferred by the RV144 regimen.

PMID- 22960792
TI  - Effect of cigarette smoke extract on insulin transport in alveolar epithelial
      cell line A549.
AB  - BACKGROUND: The main purpose of this study was to evaluate the effect of
      cigarette smoke extract (CSE) on insulin transport in alveolar epithelial cells.
      METHODS: We first examined the effect of CSE pretreatment on cell viability, mRNA
      expression, and lamellar body structures in A549 cells. Then the effect of CSE
      pretreatment on FITC-insulin transport was examined. RESULTS: When A549 cells
      were treated with 30 MUg/ml of CSE for 48 h, the expression of some mRNAs
      abundantly expressed in type II alveolar epithelial cells such as surfactant
      protein B was significantly increased. Lamellar bodylike structures became more
      evident with CSE treatment. FITC-insulin uptake from the apical side and
      subsequent efflux to the basal side was enhanced by CSE treatment in A549 cells.
      The enhancing effect of CSE on FITC-insulin uptake was concentration-dependent
      and reversible. A concentration-dependent enhancing effect of CSE on FITC-insulin
      uptake was also observed in normal, primary cultured alveolar type II epithelial
      cells isolated from rats. CONCLUSIONS: Treatment of A549 cells by CSE may direct
      the cells to a more type II-like phenotype. In accordance with this observation,
      FITC-insulin uptake was enhanced by CSE treatment. These results may partly
      explain the higher insulin absorption from the lung in smokers than in
      nonsmokers.

PMID- 22960793
TI  - Exploiting thermodynamic data to optimize the enantioseparation of underivatized
      amino acids in ligand exchange capillary electrophoresis.
AB  - Stereoselective amino acid analysis has increasingly moved into the scope of
      interest of the scientific community. In this work, we report a study on the
      chiral separation of underivatized D,L-His by ligand exchange capillary
      electrophoresis (LECE), utilizing accurate ex ante calculations. This has been
      obtained by the addition to the background electrolytes (BGE) of NaClO(4) which
      renders the separations "all in solution processes", allowing to accurately
      calculate in advance the concentrations of the species present in solution and to
      optimize the system performances. To this aim, the formation of ternary complexes
      of Cu(2+) ion and L-lysine (L-Lys) or L-ornithine (L-Orn) with L- and D-histidine
      (His), and histamine (Hm) have been studied by potentiometry and calorimetry at
      25  degrees C and with 0.1 mol dm(-3) (KNO(3)) in aqueous solution. The ternary
      species [Cu(L)(L-His)H](+) and [Cu(L)(D-His)H](+) (where L = L-Lys or L-Orn) show
      a slight but still detectable stereoselectivity, and the determination of DeltaH
      degrees  and DeltaS degrees  values allowed the understanding of the factors
      which determine this phenomenon. The stereoselectivity showed by the protonated
      ternary species has been exploited to chirally separate D,L-His in LECE, by using
      the binary complexes of copper(II) with L-Lys or L-Orn as background electrolytes
      added with the appropriate amounts of NaClO(4).

PMID- 22960794
TI  - Development of new chromatographic tools based on A2A adenosine receptor subtype
      for ligand characterization and screening by FAC-MS.
AB  - A liquid chromatographic stationary phase containing immobilized membranes from
      cells expressing A(2A) adenosine receptor (A(2A)AR) is firstly described.
      Cellular membranes from CHO cells stably transfected with human A(2A)AR vector
      (A(2A)(+)) and from the same cell line transfected with the corresponding empty
      vector (A(2A)(-)) were entrapped on immobilized artificial membrane (IAM) support
      and packed into 6.6 mm I.D. glass columns to create A(2A)(+)-IAM and A(2A)(-)-IAM
      stationary phases. Frontal chromatography experiments on both A(2A)(+)-IAM and
      A(2A)(-)-IAM columns demonstrated the presence of a low specific interaction with
      the receptor. However, immobilized A(2A) retained its ability to specifically
      bind known ligands as demonstrated by the agreement of the calculated K(d) values
      with two different chromatographic protocols in comparison to previously reported
      data. In order to maximize the specific interaction, the same cellular membranes
      were immobilized on the inner surface of a silica capillary (40 cm * 100 MUm
      I.D.) by non-covalent interactions using the avidin-biotin coupling system to
      create two open tubular columns A(2A)(+)-OT and A(2A)(-)-OT. The open tubular
      system was characterized by ranking experiments for affinity studies in mixture
      useful for the selection of new potential candidates.

PMID- 22960795
TI  - Unraveling the role of membrane proteins Notch, Pvr, and EGFR in altering
      integrin diffusion and clustering.
AB  - The role of three membrane proteins in altering the diffusion and clustering of
      integrin receptors has been measured. Integrins are membrane proteins responsible
      for integrating intracellular and extracellular signaling events and anchoring
      cells to the extracellular matrix. The methodology used to elucidate the role of
      other membrane proteins in altering integrin diffusion and clustering combines
      fluorescence microscopy with RNA interference (RNAi), which is a technique to
      reduce the expression of a target protein. The three RNAi-targeted membrane
      proteins were epidermal growth factor receptor (EGFR), platelet-derived growth
      factor/vascular endothelial growth factor-related receptor (Pvr), and Notch. Real
      time polymerase chain reaction or quantitative immunocytochemistry was used to
      measure a reduction in mRNA or protein concentration after RNAi treatment,
      respectively. Fluorescence recovery after photobleaching showed that reducing the
      concentration of EGFR or Notch results in less constrained integrin diffusion
      and, in the case of Notch RNAi, 4 % more mobile integrins. Fluorescence resonance
      energy transfer measurements performed before and after RNAi treatments indicate
      that clustering decreases for wild-type integrin, but increases for a high-ligand
      affinity integrin mutant after reducing the expression of EGFR, Pvr, or Notch. A
      model to explain the measured changes after reducing the expression of these
      three membrane proteins involving cholesterol-enriched nanodomains is proposed.

PMID- 22960796
TI  - Properties of coatings on RFID p-Chips that support plasmonic fluorescence
      enhancement in bioassays.
AB  - Microtransponders (RFID p-Chips) derivatized with silver island film (SIF) have
      previously seen success as a platform for the quantification of low-abundance
      biomolecules in nucleic acid based assays and immunoassays. In this study, we
      further characterized the morphology of the SIF as well as the polymer matrix
      enveloping it by scanning electron microscopy (SEM). The polymer was a two-layer
      silane-based matrix engulfing the p-Chip and SIF. Through a series of SEM and
      confocal fluorescence microscopy experiments, we found the depth of the polymer
      matrix to be 1-2 MUm. The radiative effects of the SIF/polymer layer were
      assessed by fluorescence lifetime imaging (FLIM) of p-Chips coated with the
      polymer to which a fluorophore (Alexa Fluor 555) was conjugated. FLIM images
      showed an 8.7-fold increase in fluorescence intensity and an increased rate of
      radiative decay, the latter of which is associated with improved photostability
      and both of which are linked to plasmonic enhancement by the SIF. Plasmonic
      enhancement was found to extend uniformly across the p-Chip and, interestingly,
      to a depth of about 1.2 MUm. The substantial depth of enhancement suggests that
      the SIF/polymer layer constitutes a three-dimensional matrix that is accessible
      to solvent and small molecules such as fluorescent dyes. Finally, we confirmed
      that no surface-enhanced Raman scattering is seen from the SIF/polymer
      combination. The analysis provides a possible mechanism by which the SIF/polymer
      coated p-Chips allow a highly sensitive immunoassay and, as a result, leads to an
      improved bioassay platform.

PMID- 22960797
TI  - Emission ((57)Co) Mossbauer spectroscopy as a tool for probing speciation and
      metabolic transformations of cobalt(II) in bacterial cells.
AB  - The emission ((57)Co) variant of Mossbauer spectroscopy, rarely used in biology
      related studies, was applied to study binding and possible transformations of
      (57)Co(II) traces in live and dead (hydrothermally treated) cells of the
      rhizobacterium Azospirillum brasilense (strain Sp7) at T=80 K in frozen aqueous
      suspensions and as their dried residues. The Mossbauer parameters calculated from
      the spectra were compared with the similarly obtained data reported earlier for
      another A. brasilense strain, Sp245 (which differs from strain Sp7 by the
      ecological niche occupied in the rhizosphere and was found earlier to exhibit
      different metabolic responses under similar environmental conditions). Similarly
      to strain Sp245, live cells of strain Sp7, rapidly frozen 2 min and 1 h after
      their contact with (57)Co(2+) (measured in frozen suspensions), showed marked
      differences in their Mossbauer parameters, reflecting metabolic transformations
      of (57)Co(2+) occurring within an hour. However, the parameters for strains Sp7
      (this work) and Sp245 (reported earlier), obtained under similar conditions, were
      found to significantly differ, implying dissimilarity in their metabolic response
      to Co(2+). This is in line with their different metabolic responses to several
      heavy metals, including Co(2+), detected earlier using Fourier transform infrared
      spectroscopy.

PMID- 22960798
TI  - Development of chemiluminescent assays for the quantitative detection and imaging
      of 5-bromo-2'deoxyuridine-labeled DNA in parvovirus B19-infected cells.
AB  - Incorporation of exogenous analogues is a widely used method to evaluate DNA
      synthesis in cultured cells exposed to exogenous factors such as infectious
      agents. Herein, two new quantitative methodologies exploiting ultrasensitive
      chemiluminescence (CL) detection of 5-bromo-2'-deoxyuridine (BrdU) have been
      developed: a CL microscope imaging assay to evaluate BrdU labelling at single
      cell level and a CL dot-blot assay to measure the amounts of DNA produced in the
      course of an in vitro infection of proliferating cells. The assays have been
      optimized on UT7/EpoS1 cells cultured in presence of different concentrations of
      BrdU (from 3 to 100 MUM) and used to monitor parvovirus B19 (B19) life cycle in
      infected cells. The CL microscope imaging assay provided a detailed localization
      of BrdU-labelled nuclei allowing to count positive cells and measure their
      related CL intensity signals. The CL dot-blot assay, coupled with a B19 capture
      procedure performed with a specific peptide nucleic acid probe, has been designed
      to discriminate and selectively quantify cellular and viral BrdU-labelled
      genomes. Quantitative evaluation of BrdU-labelled B19 DNA has been achieved by
      means of a CL calibration curve. The high detectability, down to 2 * 10(6) B19
      genome copies, and the linear range extending up to 5 * 10(8) copies make the
      method suitable to evaluate the amounts of B19 DNA produced throughout a
      replicative viral cycle.

PMID- 22960799
TI  - Role of GABA and serotonin coupled chitosan nanoparticles in enhanced hepatocyte
      proliferation.
AB  - The development of nanoparticles containing active molecules having improved
      stability, sustained release and maximum half life helps in cell proliferation
      result in enhanced tissue regeneration. Our study focuses on the use of Gamma
      amino butyric acid (GABA) and serotonin (5-HT) coupled chitosan nanoparticles for
      the active liver regeneration in male Wistar rats. The nanoparticles were
      prepared and the morphology was studied using SEM. The FT-IR spectra of the
      nanoparticles and the maximum encapsulation efficiency of GABA and 5-HT binding
      to chitosan nanoparticles were observed. The in vitro release studies provided
      the percentage release of GABA and 5-HT from the nanoparticles at different time
      intervals. The quantification of DNA and protein syntheses was done using [(3)H]
      thymidine and [(3)H] leucine uptake studies that determined the enhancement in
      hepatocyte proliferation. Our results project the role of GABA and 5-HT chitosan
      nanoparticles in the treatment of liver based diseases.

PMID- 22960801
TI  - Fliker injuries in children.
AB  - The Fliker, the new version of the foot-propelled scooter, has emerged as an
      increasingly popular recreational activity for children. This increase in
      popularity has led to a number of attendances to our tertiary paediatric
      emergency department (ED) with Fliker-associated injuries. The aim of this study
      was to examine the incidence and type of such injuries. This was a prospective
      descriptive study of all children (aged 0-16 years) attending the ED during a
      summer with Fliker-related injuries. Patients were identified through the ED
      Symphony Information System. Clinical notes of identified patients were
      investigated for the mechanism, location and type of injury. The clinical outcome
      of identified patients was also determined. Eighty patients, 39 boys (48.8%) and
      41 girls (51.2%), were identified in the study period. The mean age of the
      patients was 7.9 years (range from 2 to 13 years). Upper limb injuries were most
      common, found in 33 (41.2%) children. There were 12 head injuries. The rest
      sustained lower limb injuries, soft tissue lacerations and dental injuries. The
      Fliker is one of a number of fad recreational activities to have emerged in
      recent times. Similar to some of its predecessors (e.g. Heelys, rollerblades), it
      is associated with a spectrum of injuries in children.

PMID- 22960800
TI  - Stimulation of healing within a rabbit calvarial defect by a PCL/PLGA scaffold
      blended with TCP using solid freeform fabrication technology.
AB  - The purpose of this study was to investigate the healing capacity within an 8-mm
      rabbit calvarial defect using a polycaprolactone (PCL)/poly(lactic-co-glycolic
      acid) (PLGA) scaffold blended with tri-calcium phosphate (TCP) that was
      constructed using solid freeform fabrication (SFF) technology. The PCL/PLGA/TCP
      scaffold showed a 37 % higher compressive strength and rougher surface than the
      PCL/PLGA scaffold. In animal experiments, new bone formation was analyzed using
      microcomputed tomography (micro-CT) and histological and histometric analyses.
      The PCL/PLGA/TCP groups had significantly greater neo-tissue areas as compared
      with the control groups at 4 and 8 weeks (P < 0.05). The PCL/PLGA/TCP group had
      significantly greater bone density as compared with the control and PCL/PLGA
      groups at 4 and 8 weeks (P < 0.005). The results of this study suggest that the
      PCL/PLGA/TCP scaffold fabricated using SFF technology is useful for recovering
      and enhancing new bone formation in bony defects in rabbits.

PMID- 22960802
TI  - A telephone-based case-management intervention reduces healthcare utilization for
      frequent emergency department visitors.
AB  - BACKGROUND: A small group of frequent visitors to emergency departments accounts
      for a disproportional large number of total emergency department visits. Previous
      interventions in this population have shown mixed results. OBJECTIVE: To
      determine whether a nurse-managed telephone-based case-management intervention
      can reduce healthcare utilization and improve self-assessed health status in
      frequent emergency department users. METHODS: We carried out a Zelen-design
      randomized-controlled trial among patients who were identified as frequent
      emergency department users (>= 3 visits during the 6 months before inclusion) at
      the Karolinska University Hospital in Stockholm (Sweden). Patients included in
      the study (n = 268) were randomized to either the intervention group or the
      control group and followed for 1 year. Patients who declined to participate or
      could not be reached were also followed for the study outcome. RESULTS: The
      telephone-based case-management intervention reduced the total number of
      outpatient visits (relative risk 0.80; 95% confidence interval 0.75-0.84), the
      number of emergency department visits (relative risk 0.77; 95% confidence
      interval 0.69-0.86), the number of days patients were admitted to hospitals as
      well as the total healthcare costs for hospital admissions. There was no
      difference in mortality or other identified adverse outcomes between the
      intervention and the control groups. Patient self-assessed health status improved
      for the patients who received the case-management intervention. CONCLUSION: Our
      results indicate that the nurse-managed telephone-based case-management
      intervention represents a possible strategy to improve care for frequent
      emergency department users as well as decrease outpatient visits, admission days
      and healthcare costs.

PMID- 22960804
TI  - Bantams (Gallus gallus domesticus) also perceive a reversed Zollner illusion.
AB  - Although pigeons have been shown to be susceptible to several size and length
      illusions, other avian species have not been tested intensively for illusory
      perception. Here we report how bantams perceive the Zollner figure, in which
      parallel lines look nonparallel due to short crosshatches superimposed on the
      lines. Watanabe et al. (Cognition 119:137-141, 2011) showed that pigeons, like
      humans, perceived parallel lines as nonparallel but that the orientation of
      subjective convergence was opposite to that of humans. We trained three bantams
      to peck at the narrower (or wider) of the two gaps at the end of a pair of
      nonparallel lines. After adapting them to target lines with randomly oriented
      crosshatches (which result in no apparent illusion to humans), we tested the
      bantams' responses on randomly inserted probe trials, in which crosshatches that
      should induce the standard Zollner-like illusion for humans replaced the randomly
      oriented ones. The results suggested bantams, like pigeons, perceive a reversed
      Zollner illusion.

PMID- 22960805
TI  - Can domestic dogs (Canis familiaris) use referential emotional expressions to
      locate hidden food?
AB  - Although many studies have investigated domestic dogs' (Canis familiaris) use of
      human communicative cues, little is known about their use of humans' emotional
      expressions. We conducted a study following the general paradigm of Repacholi in
      Dev Psychol 34:1017-1025, (1998) and tested four breeds of dogs in the laboratory
      and another breed in the open air. In our study, a human reacted emotionally
      (happy, neutral or disgust) to the hidden contents of two boxes, after which the
      dog was then allowed to choose one of the boxes. Dogs tested in the laboratory
      distinguished between the most distinct of the expressed emotions (Happy-Disgust
      condition) by choosing appropriately, but performed at chance level when the two
      emotions were less distinct (Happy-Neutral condition). The breed tested in the
      open air passed both conditions, but this breed's differing testing setup might
      have been responsible for their success. Although without meaningful emotional
      expressions, when given a choice, these subjects chose randomly, their
      performance did not differ from that in the experimental conditions. Based on the
      findings revealed in the laboratory, we suggest that some domestic dogs recognize
      both the directedness and the valence of some human emotional expressions.

PMID- 22960806
TI  - Metal binding properties of the EPS produced by Halomonas sp. TG39 and its
      potential in enhancing trace element bioavailability to eukaryotic phytoplankton.
AB  - An emergent property of exopolysaccharides (EPS) produced by marine bacteria is
      their net negative charge, predominantly conferred by their high uronic acids
      content. Here, we investigated the EPS produced by an algal-associated marine
      bacterium, Halomonas sp. strain TG39, for its capacity to sequester trace metals
      and mediate their bioavailability to eukaryotic phytoplankton. Metal analysis of
      the purified EPS revealed that it contained high levels of K, Ca, Mg and several
      essential trace metals, including Zn, Cu, Fe and the metalloid Si. Desorption
      experiments with marine sediment showed that the EPS possessed a specific binding
      capacity for Ca, Si, Fe, Mn, Mg and Al. Depending on the ionic conditions, Fe was
      the third or fourth most highly-adsorbed metal out of 27 elements analyzed.
      Experiments employing Fe-limited synthetic ocean seawater showed that growth of
      the marine diatom Thalassiosira weissflogii (axenic strain) was enhanced when
      incubated in the presence of either purified EPS or EPS that had been pre-exposed
      to marine sediment, compared to non-EPS amended controls. This growth enhancement
      was attributed to the EPS binding and increasing the bioavailability of key trace
      metal elements, such as Fe(III). Since the bacterium used in this study was
      originally isolated from a marine micro-alga, this work highlights the
      possibility that bacterial associates of eukaryotic algae could be influencing
      the bioavailability of Fe(III) to phytoplankton via their production of
      polyanionic EPS. More widely, this work reinforces the potential importance of
      marine bacterial EPS in trace metal biogeochemical cycling.

PMID- 22960807
TI  - Dermatology nursing in India: the journey thus far.

PMID- 22960808
TI  - Gaining a comprehensive understanding of pruritus.
AB  - Pruritus is a common symptom associated with many dermatoses, systemic
      abnormalities, and psychiatric / psychosomatic diseases. Additionally, pruritus
      is one of the most intractable symptoms due to its complex pathogenesis involving
      an increasing number of mediators and receptors, undefined neurophysiologic
      pathways, unclear cerebral processing, and psychophysiology interaction.
      Clinically, the first challenge of dermatologists is how to get general and
      interdisciplinary vision of pruritus and to preliminarily figure it out whether
      there might be underlying systemic or psychosocial disorders. The second
      challenge is to select efficient individual tailored anti-pruritic treatment,
      which includes targeted drugs and cognitive-behavioral therapy.

PMID- 22960809
TI  - Filaggrin mutations and the skin.
AB  - Filaggrin is very important in the terminal differentiation of the skin and the
      formation of cornified envelope in the stratum corneum. Several mutations in the
      filaggrin gene have been identified in the last decade, mostly from the European
      countries. Loss of function mutations in the filaggrin gene results in reduced
      production of filaggrin, depending on the type and site of mutation. Such
      mutations in the filaggrin gene have been shown to be the most significant
      genetic risk factor for development of atopic dermatitis and undoubtedly has a
      role in the pathogenesis of ichthyosis vulgaris. Though there is theoretical
      possibility of association with hand eczema and allergic contact dermatitis; in
      clinical studies, the strength of these associations was not significantly
      strong. In this review, we have discussed the structure and function of
      filaggrin, basic genetics, type of mutations in filaggrin gene, and association
      of such mutations with different dermatoses.

PMID- 22960810
TI  - Contact allergy to topical corticosteroids and sunscreens.
AB  - Topical corticosteroids and sunscreens are extensively used formulations, both as
      over-the-counter products and as prescription medicines. Topical corticosteroids
      are increasingly being recognized as causes of allergic contact dermatitis.
      Because of their anti-inflammatory property, contact allergy to these agents may
      be difficult to suspect and prove. With corticosteroid allergy, there are special
      issues in patch testing that need to be considered: Screening tests need to be
      done with budesonide and tixocortol pivalate, and delayed readings are essential
      to pick up all positive cases. Preventive advice needs to be tailored according
      to the structural and chemical peculiarities of a particular molecule. Sunscreen
      allergy is a significant part of cosmetic allergy; especially in cases of
      photoallergic reactions. Each passing decade is bringing forth new allergens in
      this class. In many countries, benzophenones have recently been replaced by
      octocrylene as the leading causes of contact dermatitis to sunscreens. This
      article provides a broad overview of corticosteroid and sunscreen allergy so that
      the readers are aware of these important emerging classes of allergens.

PMID- 22960811
TI  - Parthenium dermatitis in India: past, present and future.
AB  - Parthenium dermatitis is an immuno-inflammatory disease caused by Parthenium
      hysterophorus and is the commonest cause of plant dermatitis in India. It is
      caused by airborne dry and friable plant particles including trichomes, and the
      most important allergens responsible for allergic contact dermatitis are
      sesquiterpene lactones. The combined type IV and type I hypersensitivity to
      parthenium has been recently postulated. In sensitized individuals, it can cause
      a spectrum of clinical patterns, such as classical airborne pattern, chronic
      actinic dermatitis-like presentation, mixed pattern dermatitis, exfoliative
      dermatitis, widespread dermatitis, and other rare patterns. There is definite
      trend towards change from airborne pattern to chronic actinic pattern in natural
      history of parthenium dermatitis. Contact sensitivity to parthenium is
      everlasting, and hence the disease runs a chronic course with exacerbation during
      summers. Patch testing with acetone or aqueous plant extract is the simplest way
      of confirming parthenium contact allergy. Management includes avoiding contact
      with allergen, managing dermatitis with topical corticosteroids/tacrolimus, and
      other immunosupressives like azathioprine. In future, we expect parthenium
      dermatitis to become less prevalent due to rapid urbanization and possible
      development of new biological methods to eradicate the parthenium. Genetic
      factors associated with susceptibility to parthenium dermatitis need to be
      studied.

PMID- 22960812
TI  - Hand eczema: an update.
AB  - Eczema, the commonest disorders afflicting the hands, is also the commonest
      occupational skin disease (OSD). In the dermatology outpatient departments, only
      the severe cases are diagnosed since patients rarely report with early hand
      dermatitis. Mild forms are picked up only during occupational screening. Hand
      eczema (HE) can evolve into a chronic condition with persistent disease even
      after avoiding contact with the incriminated allergen / irritant. The important
      risk factors for hand eczema are atopy (especially the presence of dermatitis),
      wet work, and contact allergy. The higher prevalence in women as compared to men
      in most studies is related to environmental factors and is mainly applicable to
      younger women in their twenties. Preventive measures play a very important role
      in therapy as they enable the affected individuals to retain their employment and
      livelihood. This article reviews established preventive and therapeutic options
      and newer drugs like alitretinoin in hand eczema with a mention on the etiology
      and morphology. Identifying the etiological factors is of paramount importance as
      avoiding or minimizing these factors play an important role in treatment.

PMID- 22960813
TI  - Contact dermatitis to hair dye: an update.
AB  - Exposure to hair dyes has long been known as a significant risk factor for
      development of allergic contact dermatitis among the exposed population as these
      lead to severe eczema of face and upper trunk in the consumer and hand eczema in
      hair-dressers. Currently, para-phenylenediamine (PPD) is the main ingredient used
      in permanent hair color products in the market and is the most important
      allergen. Prevalence of PPD sensitization is high in patients with contact
      dermatitis across all continents, with hair dye use being the commonest cause. In
      order to decrease the burden of disease, use of alternative natural dyeing agents
      among consumers and use of barrier neoprene gloves among hairdressers should be
      encouraged apart from stringent legislation to reduce the amount of PPD reaching
      the consumer.

PMID- 22960814
TI  - The clinical significance of immunological contact urticaria to processed grains.
AB  - Contact urticaria, is characterized by an urticarial wheal-and-flare reaction at
      the site of contact by an allergen. Immunological contact urticaria, while less
      common than non-immunological contact urticaria, has more potentially serious
      consequences, and therefore, its recognition and treatment is important.
      Immunological contact urticaria is a type I hypersensitivity reaction. Potential
      complications include organ system involvement other than skin and even
      anaphylaxis and death. A vast majority of immunological contact urticaria is work
      related. We will discuss the definition of immunological contact urticaria, the
      mechanism of the contact urticarial reaction, contact urticaria in the
      occupational setting, and the role of grains in contact urticaria. Testing and
      treatment are also briefly discussed.

PMID- 22960815
TI  - Oral drug provocation test to generate a list of safe drugs: experience with 100
      patients.
AB  - BACKGROUND: Following a drug eruption, patients and their doctors need to know
      which drugs can be safely administered for subsequent illnesses. Currently
      available laboratory tests are unable to answer this question in a clinically
      meaningful manner. AIMS: To describe our use of oral provocation tests to provide
      a list of safe drugs to patients. METHODS: We studied the records of 100 patients
      who underwent oral provocation testing in our department between 2003 and 2009.
      All patients were admitted to hospital and drugs were administered under
      supervision, one drug per day. A dermatologist evaluated all symptoms and signs
      that developed following drug intake. RESULTS: Sixty nine women and 31 men
      underwent provocation testing. There were 96 reactions in 61 patients, of which
      44 reactions in 34 patients were judged to be true reactions. All reactions could
      be controlled, with treatment or spontaneously. A list of safe drugs was provided
      to the patient along with written instructions to avoid any drug(s) that had
      produced a reaction. CONCLUSIONS: Oral provocation tests are safe and effective
      in providing patients with a list of drugs they can take safely. These tests
      should preferably be undertaken after admitting the patient to hospital.

PMID- 22960816
TI  - Development of melanocye-keratinocyte co-culture model for controls and vitiligo
      to assess regulators of pigmentation and melanocytes.
AB  - BACKGROUND: There is a need to develop an in vitro skin models which can be used
      as alternative system for research and testing pharmacological products in place
      of laboratory animals. Therefore to study the biology and pathophysiology of
      pigmentation and vitiligo, reliable in vitro skin pigmentation models are
      required. AIM: In this study, we used primary cultured melanocytes and
      keratinocytes to prepare the skin co-culture model in control and vitiligo
      patients. METHODS: The skin grafts were taken from control and patients of
      vitiligo. In vitro co-culture was prepared after culturing primary melanocytes
      and keratinocytes. Co- cultures were treated with melanogenic stimulators and
      inhibitors and after that tyrosinase assay, MTT assay and melanin content assay
      were performed. RESULTS: Melanocytes and keratinocytes were successfully cultured
      from control and vitiligo patients and after that co-culture models were
      prepared. After treatment of co-culture model with melanogenic stimulator we
      found that tyrosinase activity, cell proliferation and melanin content increased
      whereas after treatment with melanogenic inhibitor, tyrosinase activity, cell
      proliferation and melanin content decreased. We also found some differences in
      the control co-culture model and vitiligo co-culture model. CONCLUSION: We
      successfully constructed in vitro co-culture pigmentation model for control and
      vitiligo patients using primary cultured melanocytes and keratinocytes. The use
      of primary melanocytes and keratinocytes is more appropriate over the use of
      transformed cells. The only limitation of these models is that these can be used
      for screening small numbers of compounds.

PMID- 22960817
TI  - Comparative efficacy and safety of topical permethrin, topical ivermectin, and
      oral ivermectin in patients of uncomplicated scabies.
AB  - BACKGROUND: Ivermectin has opened a new era in the management of scabies as
      orally effective drug. However, topical route has been little explored for
      ivermectin. AIMS: To compare the efficacy and safety of topical permethrin, oral
      ivermectin, and topical ivermectin in the treatment of uncomplicated scabies.
      METHODS: This was an open-label, randomized, comparative, parallel clinical trial
      conducted in 315 patients, randomly allocated to 3 groups. First group received
      permethrin 5% cream as single application, second group received tablet
      ivermectin 200 mcg/kg as single dose, and third group received ivermectin 1%
      lotion as single application. All the patients received anti-histaminic for
      pruritus. The patients were followed up at intervals of 1, 2, 3, and 4 weeks. If
      there were no signs of cure, the same intervention was repeated at each follow
      up. Primary efficacy variable was clinical cure of lesions. Statistical analysis
      was done by chi square test and one way ANOVA test using SPSS version 12.
      RESULTS: At the end of first week, cure rate was 74.8% in permethrin group, 30%
      in oral ivermectin group, and 69.3% in topical ivermectin group (P < 0.05). At
      the end of second week, cure rate was 99% in permethrin group, 63% in oral
      ivermectin group, and 100% in topical ivermectin group (P < 0.05). At the end of
      third week, 100% cure rate was observed in permethrin and topical ivermectin
      group while 99% in oral ivermectin group (P = 0.367). No serious adverse events
      were observed. CONCLUSIONS: Permethrin and topical ivermectin were equally
      effective against scabies while oral ivermectin was significantly less effective
      up to 2 weeks. Topical ivermectin can be used as an alternative to permethrin.

PMID- 22960818
TI  - Psoriatic alopecia - fact or fiction? A clinicohistopathologic reappraisal.
AB  - BACKGROUND: The incidence of psoriatic alopecia in psoriatic patients is
      underwhelming, given the prevalence of psoriasis in the North American
      population. Recently, a 60-year-old Albanian female, lacking a significant
      medical history for psoriasis, presented to our clinic with a 1-year history of
      "dandruff" associated with itch, hair thinning, and histopathologic evidence
      consistent with prior reports of "psoriatic alopecia." AIMS: The absence of
      preceding or concomitant psoriasis suggests that the patient's alopecia is an
      antecedent manifestation of psoriasis, thus prompting this retrospective study to
      ascertain better the relationship between alopecia and psoriasis. METHODS: We
      performed a retrospective review of 33 scalp biopsies on 31 patients having
      histopathologic diagnosis of psoriasis belonging to 31 patients seen between 2007
      and 2010. RESULTS: Alopecia was a presenting feature in 48% of cases with
      definitive clinical and/or histopathologic diagnosis of psoriasis (scale crust
      with neutrophils, psoriasiform epidermal hyperplasia, and hypogranulosis). The
      most common follicular-related changes were infundibular dilatation (87%)
      followed by perifollicular fibrosis (77%), perifollicular lymphocytic
      inflammation (68%), thinning of the follicular infundibulum (55%), and fibrous
      tracts (28%). Of interest, sebaceous glands were absent in 60% and atrophic in
      25% of cases. CONCLUSION: While a major limitation of this study is that it is a
      retrospective one, given that these changes are common to varying degrees in all
      lymphocytic scarring alopecias, we posit that psoriatic alopecia likely
      represents a secondary clinical change to a primary process and is not a unique
      histopathologic entity. A prospective study with a control group that includes
      lymphocytic scarring alopecias from non-psoriatic patients is required to support
      our findings.

PMID- 22960819
TI  - Subungual hyperkeratosis nail biopsy: a better diagnostic tool for onychomycosis.
AB  - BACKGROUND: Onychomycosis is one of the most common nail disorders. Mycological
      examination by potassium hydroxide (KOH) mount and fungal culture is the most
      commonly used diagnostic method. However, it is associated with a low
      sensitivity. AIMS: To evaluate the technique of subungual hyperkeratosis nail
      biopsy in diagnosing onychomycosis in HIV-infected and immunocompetent adults and
      compare it with mycological examination. METHODS: 34 HIV-positive patients who
      presented clinically with onychomycosis were recruited in the study from the
      beginning. There was no screening done for patients with onychomycosis. This has
      been clarified in manuscript under the heading of methods. RESULTS: All the
      fungal cultures yielded dermatophytes correlating with the biopsy findings. Only
      hyphal form of fungus was detected in KOH examination, indicating it was not a
      contaminant. Clinical types of onychomycosis are stated in discussion.
      CONCLUSIONS: PAS stain of subungual hyperkeratosis nail biopsy was the most
      sensitive in the diagnosis of onychomycosis in both HIV-infected and non-infected
      groups.

PMID- 22960820
TI  - Peeling skin syndrome in eight cases of four different families from India and
      Bangladesh.
AB  - Peeling skin syndrome (PSS) is a rare recessively inherited ichthyosiform
      genodermatoses characterized by superficial skin peeling. This has 2 subtypes,
      acral (APSS; OMIM 609796) and generalized form (OMIM 270300). The later has been
      subdivided into type A (non-inflammatory) and type B (inflammatory). Eight cases
      of peeling skin syndrome in 4 families were recorded over a period of 5 years.
      They were diagnosed clinically and confirmed histopathologically. Disease onset
      ranged from birth to childhood age (mean 5.25 +/- 4.528 years) and age at
      presentation ranged from 7-35 years (mean 23.25 +/- 10.471 years). Males
      outnumbered females (M:F - 5:3). All had non-inflammatory generalized disease of
      type-A PSS variety, except one who had type-B PSS. Two Muslim families (1 st and
      2 nd family, total 5 patients) came from nearby country Bangladesh, and the 2
      Hindu families were Indian. Higher severity over acral areas in generalized type,
      possible autosomal dominant pattern of inheritance and improvement with age as
      found in this series were new manifestations and possibly unreported previously.
      The disease was found to be poorly responsive to oral retinoids. Prevalence of
      the disease may be higher than expected. Importance of mutational analysis was
      also highlighted.

PMID- 22960821
TI  - Childhood pemphigus vulgaris successfully treated with rituximab.
AB  - Pemphigus is a potentially fatal autoimmune epidermal bullous disorder. Rituximab
      is a novel therapy for the treatment of refractory pemphigus. However, there is
      limited clinical data on safety and efficacy of rituximab in pediatric age group.
      Herein, we report an 11-year-old boy of childhood pemphigus vulgaris who failed
      to respond to dexamethasone pulse therapy and was subsequently treated with
      rituximab and achieved complete remission.

PMID- 22960822
TI  - Yellow plaques as cutaneous markers of internal disorders.

PMID- 22960823
TI  - Sensitivity and specificity of the trichoscopy.

PMID- 22960824
TI  - Pseudopelade of Brocq in two brothers: possible role of hereditary factors in the
      pathogenesis.

PMID- 22960825
TI  - D66H mutation in GJB2 gene in a Chinese family with classical Vohwinkel syndrome.

PMID- 22960826
TI  - Nickel free safety pins: a boon to women with nickel allergy.

PMID- 22960827
TI  - Melanoma arising in giant zosteriform nevus spilus.

PMID- 22960828
TI  - Delusional infestation with fungus.

PMID- 22960829
TI  - Palmoplantar fibromatosis with nail dystrophy.

PMID- 22960830
TI  - Highly aggressive Buschke-lowenstein tumor of the perineal region with fatal
      outcome.

PMID- 22960831
TI  - Elephantiasis nostras verrucosa: a rare case of thyroid dermopathy.

PMID- 22960832
TI  - Cutaneous lymphadenoma.

PMID- 22960833
TI  - Generalized morphea developing in a patient previously affected with eosinophilic
      fasciitis.

PMID- 22960834
TI  - Triads in dermatology.

PMID- 22960835
TI  - Cauliflower like growth in the groins.

PMID- 22960836
TI  - Oxidative stress and leukocyte migration inhibition response in cutaneous adverse
      drug reactions.
AB  - BACKGROUND: Cutaneous adverse drug reactions (CADRs) may either be immunological
      or non-immunological. The precise mechanisms, however, are largely obscure. Other
      concomitant mechanisms may amplify and/or contribute to the severity and duration
      of a reaction. One such mechanism could be oxidative stress, a state of imbalance
      between reactive oxygen species, and their subsequent detoxification by
      antioxidants. AIMS: (a) to assess the oxidative stress status in the blood of
      cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and
      malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition
      (LMI) response in these patients in response to the suspected drug (s), and (c)
      to look for the association between oxidative stress parameters and LMI. METHODS:
      Ethical committee approval was obtained for this study. Fresh venous blood
      samples were obtained from the patients of CADRs (group A) during the acute phase
      of reaction and healthy control subjects (group B). MDA levels, a measure of
      oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant
      capacity, were assayed in the blood samples of both groups using
      spectrophotometry. LMI response was measured by challenging the patients'
      peripheral blood mononuclear cells with the suspected drug to confirm
      immunological perturbation. RESULTS: Totally 66 participants, 33 cases in group A
      and equal number of controls in group B, were studied. The mean MDA levels were
      found to be raised (P < 0.001), but GSH levels were significantly reduced in
      group A when compared with group B (P = <0.001). LMI response against drug(s) was
      performed in 33 cases (group A), out of which 25 cases showed a positive LMI
      response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25),
      exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25),
      vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to
      be significantly higher in the LMI positive CADRs (P < 0.001) when compared with
      LMI-negative ones, while no significant difference was seen for GSH (P = 0.100).
      Furthermore, there was a significant positive correlation between MDA levels and
      LMI response (r = 0.831, P < 0.001). On the other hand, a negative but
      statistically insignificant correlation was found between GSH and LMI response (r
      = -0.248, P = 0.271). CONCLUSION: CADR patients were found to be under oxidative
      stress based on MDA and GSH levels in the peripheral blood. There is a
      significant positive correlation of LMI response (against the causative drug)
      with MDA levels, which strongly associates oxidative stress with the
      immunopathogenesis in CADRs.

PMID- 22960837
TI  - Role of occasional evaluation of the skin in early detection of melanoma in
      elderly patients.

PMID- 22960838
TI  - Primary cutaneous sarcomatoid carcinoma.

PMID- 22960839
TI  - Metachronous multiple primary malignant neoplasms in a patient with
      dermatomyositis.

PMID- 22960840
TI  - Migratory "moles" - dermoscopic diagnosis.

PMID- 22960841
TI  - Ripple-pattern melanotrichoblastoma arising within nevus sebaceus.

PMID- 22960842
TI  - Radiotherapy-induced koebnerization in lichen planus.

PMID- 22960843
TI  - Basal cell nevus syndrome: a rare entity.

PMID- 22960844
TI  - Alveolar soft part sarcoma presenting as metastatic nodule on the nose.

PMID- 22960845
TI  - Isolated plantar cerebriform collagenoma.

PMID- 22960846
TI  - Yellowish face mask in a child: a local side-effect of inhaled corticosteroids?

PMID- 22960847
TI  - Interstitial lung disease probably caused by imipramine.
AB  - Drugs are rarely associated with causing interstitial lung disease (ILD). We
      report a case of a 75-year-old woman who developed ILD after exposure to
      imipramine. To our knowledge, this is one of the rare cases of ILD probably
      caused due to imipramine. There is need to report such rare adverse effects
      related to ILD and drugs for better management of ILD. 

PMID- 22960848
TI  - Management of gouty arthritis in patients with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a comorbid condition that affects, based on
      recent estimates, between 47% and 54% of patients with gouty arthritis. However,
      data from randomized controlled trials in patients with gouty arthritis and CKD
      are limited, and current gouty arthritis treatment guidelines do not address the
      challenges associated with managing this patient population. Nonsteroidal anti
      inflammatory drugs and colchicine are recommended first-line treatments for acute
      gouty arthritis attacks. However, in patients with CKD, nonsteroidal anti
      inflammatory drugs are not recommended because their use can exacerbate or cause
      acute kidney injury. Also, colchicine toxicity is increased in patients with CKD,
      and dosage reduction is required based on level of kidney function. Allopurinol,
      febuxostat, and pegloticase are all effective treatments for controlling elevated
      uric acid levels after the treatment of an acute attack. However, in patients
      with CKD, required allopurinol dosage reductions may limit efficacy; pegloticase
      requires further investigation in this population, and febuxostat has not been
      studied in patients with creatinine clearance<30 mL/min. This article reviews the
      risks and benefits associated with currently available pharmacologic agents for
      the management of acute and chronic gouty arthritis including urate-lowering
      therapy in patients with CKD. Challenges specific to primary care providers are
      addressed, including guidance to help them decide when to collaborate with, or
      refer patients to, rheumatology and nephrology specialists based on the severity
      of gout and CKD.

PMID- 22960849
TI  - Syncope: Approaches to Diagnosis and Management.
AB  - Syncope is defined as a transient loss of consciousness due to cerebral
      hypoperfusion followed by spontaneous recovery. Common causes of syncope include
      vasovagal syncope, situational syncope, orthostatic hypotension, carotid sinus
      hypersensitivity, left- and right-sided obstructive cardiac lesions, and cardiac
      arrhythmias. History and physical examination often provide valuable clues about
      the underlying etiology of syncope. Admission decisions in the emergency
      department can be guided by various risk prediction scores. Evaluation of a
      patient with syncope involves a large battery of diagnostic tests that include a
      12-lead electrocardiogram, Holter monitoring, echocardiogram, tilt table testing,
      ischemia evaluation, electrophysiologic studies, and other imaging tests. Despite
      the availability of these advanced diagnostic tests, a significant proportion of
      patients with syncope remain undiagnosed. Therapy should be tailored based on the
      underlying etiology of syncope. 

PMID- 22960850
TI  - Monoamine oxidase inhibitors and neuroprotection:  a review.
AB  - Monoamine oxidase inhibitors have been available for more than 50 years,
      initially developed as antidepressants but currently used in a variety of
      psychiatric and neurological conditions. There has been a recent surge of
      interest in monoamine oxidase inhibitors because of their reported
      neuroprotective and/or neurorescue properties. Interestingly, it seems that often
      these properties are independent of their ability to inhibit monoamine oxidase.
      This review article presents an overview of the neuroprotective/neurorescue
      properties of these multifaceted drugs and focuses on phenelzine, (-)-deprenyl,
      rasagiline, ladostigil, tranylcypromine, moclobemide, and clorgyline and their
      possible neuroprotective mechanisms.

PMID- 22960851
TI  - Comment to the response to "severe pernicious anemia with distinct cytogenetic
      and flow cytometric aberrations mimicking myelodysplastic syndrome".

PMID- 22960852
TI  - No evidence of hemostasis disturbance in Thai children with iron deficiency
      anemia.

PMID- 22960853
TI  - Necrotizing fasciitis in myelodysplastic syndrome: an exceptionally rare
      occurrence.

PMID- 22960855
TI  - Mission impossible to mission control.

PMID- 22960856
TI  - Hearing loss, auditory neuropathy, and neurological co-morbidity in children with
      birthweight <750 g.
AB  - BACKGROUND AND AIMS: The current literature considers a birthweight <1,500 g as a
      risk factor for sensorineural hearing loss (SNHL, hearing threshold >25
      decibels), auditory neuropathy (AN), and several neurological sequelae. The aim
      of the study was to determine the frequency and risk factors associated with
      SNHL, AN, and neurological morbidity in a group of children with birthweights of
      <750 g treated at a neonatal care unit and recruited into a long-term follow-up
      program. METHODS: A case-control study was carried out. Inclusion criteria were
      birthweight <750 g and born between the years 2000 and 2010. We performed
      brainstem auditory-evoked potentials (BAEP), evoked otoacoustic emissions (EOAE)
      and free-field audiometry (FFA) in this population. Neonatal variables and
      procedures were compared between children with SNHL and children with normal
      bilateral hearing (NBH). RESULTS: A total of 93 children with a mean age of 4
      years were included in the follow-up. Six children (6.4%) had SNHL and 87 had
      NBH. We were unable to identify AN in the sample. Mean weight for this sample was
      673 +/- 68 g and gestational age 27.5 +/- 2 weeks. Variables reflecting
      differences between groups included days under mechanical ventilation, furosemide
      treatment, and bronchopulmonary dysplasia. In the SNHL group, three patients had
      periventricular leukomalacia, two had hydrocephalus, and one patient had cerebral
      palsy. CONCLUSIONS: Frequency of SNHL in children with birthweights <750 g was
      higher than in other premature infants and was related with mechanical
      ventilation, furosemide application, and bronchopulmonary dysplasia. Association
      with other neurological morbidities was frequent. Early diagnosis and
      intervention are required.

PMID- 22960854
TI  - Global probabilistic annotation of metabolic networks enables enzyme discovery.
AB  - Annotation of organism-specific metabolic networks is one of the main challenges
      of systems biology. Importantly, owing to inherent uncertainty of computational
      annotations, predictions of biochemical function need to be treated
      probabilistically. We present a global probabilistic approach to annotate genome
      scale metabolic networks that integrates sequence homology and context-based
      correlations under a single principled framework. The developed method for global
      biochemical reconstruction using sampling (GLOBUS) not only provides annotation
      probabilities for each functional assignment but also suggests likely alternative
      functions. GLOBUS is based on statistical Gibbs sampling of probable metabolic
      annotations and is able to make accurate functional assignments even in cases of
      remote sequence identity to known enzymes. We apply GLOBUS to genomes of Bacillus
      subtilis and Staphylococcus aureus and validate the method predictions by
      experimentally demonstrating the 6-phosphogluconolactonase activity of YkgB and
      the role of the Sps pathway for rhamnose biosynthesis in B. subtilis.

PMID- 22960857
TI  - Curtailing overexpression of E2F3 in breast cancer using siRNA (E2F3)-based gene
      silencing.
AB  - BACKGROUND AND AIMS: The E2F3 transcription factor claims its role in controlling
      cell cycle progression. As reported earlier, nuclear E2F3 overexpression leads to
      development of bladder and prostate cancer in humans. Accordingly, the present
      investigation has been designed to assess to what extent E2F3 would be
      overexpressed in breast cancer. The aim of this study was to emphasize that the
      levels of E2F3 are increased in breast cancer and highlights the efficacy of
      siRNA targeted to E2F3. METHODS: To investigate the expression level of E2F3 and
      the progression of breast tumors, quantitative real-time PCR analysis was carried
      out. Western blotting analysis was performed to measure its counterparts, namely,
      E2F3a and E2F3b. RESULTS: In the novel axis of E2F3, a large set of 11 breast
      cancer cell lines were identified to have the property of overexpression.
      Furthermore, the small interfering RNA (siRNA) developed against E2F3
      significantly blocked the expression of the E2F3 in the selected breast cancer
      cell lines. Thus, the present findings authenticate the efficiency of siRNA
      (E2F3) to fight against breast cancer; hence, the siRNA mediated E2F3 gene
      silencing knockdown the E2F3. CONCLUSIONS: This in vitro study demonstrates that
      E2F3 is a newly identified diagnostic and potential therapeutic target in breast
      cancer. Outcomes of this study affirm that siRNA for E2F3 facilitates the
      silencing of E2F3 overexpression and fights against breast cancer. Therefore, it
      plays a vital role as an alternative for diagnosis and clinical outcome for the
      treatment of breast cancer.

PMID- 22960859
TI  - Immune response to seasonal influenza A virus infection: a proteomic approach.
AB  - BACKGROUND AND AIMS: Influenza viruses cause respiratory infection in humans and
      result in substantial illness, death, and economic burden. To date, however, the
      mechanisms by which these viruses cause disease are not fully understood.
      METHODS: To investigate the proteomic profile of children infected with seasonal
      influenza A virus, nasal aspirates derived from children (n = 12) experiencing
      flu symptoms caused by seasonal influenza A virus were analyzed using two
      dimensional electrophoresis (2-DE). Control nasal samples were taken from the
      same group of children 8-10 weeks later when they were symptom free. RESULTS:
      Analysis of the 2-DE gels revealed eight spots differentially expressed, which
      were further analyzed using mass spectrometry. Ten proteins were found to be
      differentially upregulated in the infected children including PLUNC, cystatin S,
      cystatin SA, S100A9, lipocalin 1 fragments (n = 2), truncated lactotransferrin,
      two immunoglobulin (Ig) kappa fragments and one immunoglobulin (Ig) lambda
      fragment. CONCLUSIONS: Our findings reveal that the composition of nasal
      secretions in influenza virus respiratory infections is different from that when
      children are healthy and may provide further insights into the pathogenesis of
      respiratory infections caused by seasonal influenza A viruses.

PMID- 22960860
TI  - Evaluation of PDE5 and PDE9 expression in benign and malignant breast tumors.
AB  - BACKGROUND AND AIMS: Phosphodiesterases 5 and 9 (PDE5, PDE9) are enzymes
      responsible for regulating second messenger signaling by hydrolyzing 3',5' cyclic
      guanosine monophosphate (cGMP). PDE isoforms are deregulated in some types of
      human cancer. The present study was carried out to evaluate the expression of
      phosphodiesterase isoenzymes, PDE5 and PDE9, in benign and malignant breast
      tumors. METHODS: The expression levels of PDE5 and PDE9 were assayed in malignant
      and benign breast tumors and corresponding normal breast tissues using
      quantitative real-time RT-PCR. Moreover, the correlation between PDE5, PDE9
      relative expression and clinicopathological characteristics were analyzed.
      RESULTS: The relative expressions of PDE5 and PDE9 in malignant tumors were
      significantly higher than those of respective normal breast tissues and benign
      tumors (5.5-fold, p <0.001 and 6-fold, p <0.001, respectively). Furthermore, a
      significant positive correlation was found between PDE5 and PDE9 overexpression
      and tumor grade, stage, and lymph node involvement. However, a negative
      correlation was observed with age. CONCLUSIONS: Based on the present results, it
      is concluded that assessment of PDE5 and PDE9 expression may be useful in the
      differential diagnosis of benign and malignant breast disease and successful
      treatment of breast cancer. To the best of our knowledge, this is the first study
      to show that PDE5 and PDE9 expression levels are higher in malignant breast
      tumors than those of normal and benign breast tissue.

PMID- 22960861
TI  - Role of TRPC3 channel in human internal mammary artery.
AB  - BACKGROUND AND AIMS: Intracellular calcium regulation in endothelial cells
      depends on transient receptor potential channels (TRPs). Canonical TRPs (TRPCs)
      are now recognized as the most important Ca(2+)-permeable cation channels in
      vascular endothelium and TRPC3 channel is reported to play a role in vasodilation
      in animal vessels. However, little is known about the role of TRPCs in human
      arteries. We therefore tested the hypothesis that TRPCs play a role in human
      arteries. METHODS: Cumulative concentration-relaxation curves to acetylcholine (
      11 to -4.5 log M) were established in the human internal mammary artery (IMA)
      rings (n = 42) taken from 28 patients undergoing coronary artery bypass grafting
      in precontraction induced by U46619 (-8 log M) in the absence or presence of
      SKF96365 (10 MUmol/L) or Pyr3 (3 MUmol/L). Protein expressions of TRPC3 were
      determined by Western blot and immunohistochemistry staining. RESULTS: The
      maximal relaxation induced by acetylcholine was significantly attenuated by the
      nonspecific cation channels inhibitor, SKF96365 (48.2 +/- 3.7 vs. 66.0 +/- 0.9%
      in control, p <0.01) or the selective TRPC3 blocker, Pyr3 (58.4 +/- 2.3% vs. 67.7
      +/- 1.1% in control, p <0.01). Protein expression of TRPC3 was detected in human
      IMA. CONCLUSIONS: TRPC3 exists and plays a role in the acetylcholine-induced
      endothelium-dependent relaxation in the human IMA. This study suggests that TRPC3
      may be a potential new target in endothelial protection in patients with
      endothelial dysfunction such as in patients with coronary artery disease in order
      to improve the long-term patency of the grafting vessels.

PMID- 22960862
TI  - Acceptor pincer Ru(II) chemistry.
AB  - A series of new acceptor pincer Ru(II) complexes are reported. The carbonyl
      complex ((CF(3))PCP)Ru(CO)Cl(2)(-)Et(3)NH(+) is obtained from the reaction of
      (CF(3))PCPH with [(cod)Ru(MU-Cl)(2)](n). Chloride displacement with (CF(3))PCPH,
      CO, PPh(3), or C(2)H(4) gave complexes of the type ((CF(3))PCP)Ru(CO)(L)Cl, or in
      the case of (CF(3))PCPH, the bridged dimeric complex [((CF(3))PCP)Ru(CO)Cl](2)(MU
      (CF(3))PCPH). Chloride abstraction from ((CF(3))PCP)Ru(CO)(L)Cl, L = CO or PPh(3)
      by (Et(3)Si)(2)(MU-H)(+)B(C(6)F(5))(4)(-) followed by Et(3)N addition produced
      ((CF(3))PCP)Ru(CO)(L)(H) products. Reaction of cis-((CF(3))PCP)Ru(CO)(2)Cl with
      (Et(3)Si)(2)(MU-H)(+)B(C(6)F(5))(4)(-) in the presence of excess CO afforded
      ((CF(3))PCP)Ru(CO)(3)(+). The reaction of (CF(3))PCPH with
      (PPh(3))(3)Ru(H)(O(2)CR) (R = Me or Ph) produced the corresponding carboxylate
      complexes ((CF(3))PCP)Ru(PPh(3))(O(2)CR).

PMID- 22960863
TI  - Measuring and valuing quality of life for public health research: application of
      the ICECAP-O capability index in the Australian general population.
AB  - OBJECTIVES: To assess the applicability of the newly developed ICECAP-O
      capability index in the measurement and valuation of quality of life in a large
      community based sample of the Australian general population. With origins in
      Sen's capability theory, the ICECAP-O may more fully encapsulate the multi
      dimensional outcomes of public health policies and interventions than traditional
      health economic constructs. METHODS: 2,937 Australian residents participated in
      face-to-face interviews. The relationships between ICECAP-O scores according to
      age groups (<65 or >65 years) and socio-economic status were investigated using
      descriptive statistics and multivariable linear regression models. RESULTS: Lower
      income levels and being unemployed or physically unable to work were negatively
      associated with capability for both age groups. Capability was strongly and
      positively associated with marriage and cohabitation in the younger age group,
      whilst being Australian-born was a positive indicator for the older group.
      CONCLUSIONS: The results provide insights into the assessment of capability in
      the Australian general population. The ICECAP-O shows promise for application in
      the measurement and valuation of quality of life in general population surveys,
      and incorporation into economic evaluations of public health interventions.

PMID- 22960865
TI  - An improved synthesis of 1,2-diarylethanols under conventional heating and
      ultrasound irradiation.
AB  - A simple and efficient synthesis of 1,2-diarylethanols has been developed. The
      procedure involved the reaction between a variety of toluene derivatives and aryl
      aldehydes under conventional heating and ultrasound irradiation. This procedure
      possesses several advantages such as operational simplicity, high yield, safety
      and environment benignancy. Ultrasound was proved to be very helpful to the
      reaction, markedly improving the yield and the reaction rate.

PMID- 22960864
TI  - Towards decoding the conifer giga-genome.
AB  - Several new initiatives have been launched recently to sequence conifer genomes
      including pines, spruces and Douglas-fir. Owing to the very large genome sizes
      ranging from 18 to 35 gigabases, sequencing even a single conifer genome had been
      considered unattainable until the recent throughput increases and cost reductions
      afforded by next generation sequencers. The purpose of this review is to describe
      the context for these new initiatives. A knowledge foundation has been acquired
      in several conifers of commercial and ecological interest through large-scale
      cDNA analyses, construction of genetic maps and gene mapping studies aiming to
      link phenotype and genotype. Exploratory sequencing in pines and spruces have
      pointed out some of the unique properties of these giga-genomes and suggested
      strategies that may be needed to extract value from their sequencing. The hope is
      that recent and pending developments in sequencing technology will contribute to
      rapidly filling the knowledge vacuum surrounding their structure, contents and
      evolution. Researchers are also making plans to use comparative analyses that
      will help to turn the data into a valuable resource for enhancing and protecting
      the world's conifer forests.

PMID- 22960866
TI  - Development and characterization of EST-SSR markers from Scapharca broughtonii
      and their transferability in Scapharca subcrenata and Tegillarca granosa.
AB  - Twenty-five novel EST-derived simple sequence repeat (EST-SSR) markers were
      developed in the ark shell Scapharca broughtonii. Polymorphisms of these EST-SSR
      markers were evaluated in 48 wild individuals collected from Shidao, Shandong
      Province, China. A total of 202 alleles were detected at 25 loci. The numbers of
      alleles per locus ranged from 4 to 14, with an average of 8.08. The observed and
      expected heterozygosities varied from 0.2917 to 1.000 and from 0.3570 to 0.9002,
      respectively. After sequential Bonferroni correction for multiple tests, only one
      locus was found to deviate from Hardy-Weinberg equilibrium. Twenty-five EST-SSR
      markers showed a high rate of across-species transferability (100%) in Scapharca
      subcrenata and a low rate of across-genus transferability (20%) in Tegillarca
      granosa. These EST-SSRs will be helpful for QTL mapping, molecular breeding and
      investigation of population genetic diversity in ark shell S. broughtonii and
      other Scapharca species.

PMID- 22960867
TI  - Phenolic antioxidants isolated from the flowers of Osmanthus fragrans.
AB  - O. fragrans has slightly less antioxidative activity than green tea. Five
      phenolic compounds, tyrosyl acetate (1), (+)-phillygenin (2), (8E)-ligustroside
      (3), rutin (4), and verbascoside (5), were isolated from the CHCl3 sub-extract of
      O. fragrans. The structures were elucidated by interpreting their spectral data.
      Evaluation of the antioxidative property of the isolated (+)-phillygenin (2),
      rutin (4), and verbascoside (5) revealed strong DPPH radical scavenging activity,
      with IC50 values of 19.1, 10.3, and 6.2 MUM, respectively. These isolates also
      exhibited an H2O2 scavenging ability, with IC50 values of 10.5, 23.4, and 13.4
      MUM, respectively.

PMID- 22960868
TI  - Novel lipophilic lanthanide bis-phthalocyanines functionalized by
      pentadecylphenoxy groups: synthesis, characterization and UV-photostability.
AB  - Novel sandwich-type phthalocyanines containing a rare earth metal core (Pr, Nd,
      Eu-Lu) and macrocycles peripherally substituted by pentadecylphenoxy groups were
      synthesized using a cardanol-based phthalonitrile precursor and the respective
      lanthanide acetate. Additionally, the metal free-base analog compound was studied
      for comparison. The purified reaction products were all found to be thick and
      viscous substances at room temperature, showing liquid crystalline behavior with
      a distinct increase in fluidity at ca. 40  degrees  C. The complexes are readily
      soluble in chloroalkyl solvents and dissolve fairly well in DMF with some
      tendency to form aggregates. Besides they are strongly hydrophobic and reveal a
      peculiar affinity for lipophilic media. The compounds have been characterized by
      UV-Vis (absorption and emission), FTIR, MS and DSC methods. Photochemical
      activity in the liquid phase (dimethylformamide, dichloromethane, mineral oil)
      and the degree of photodegradation demonstrated under constant UV-irradiation
      (lambda = 352 nm) have been analyzed and discussed in terms of photostability.

PMID- 22960869
TI  - Endophytic fungi produce gibberellins and indoleacetic acid and promotes host
      plant growth during stress.
AB  - We isolated and examined two endophytic fungi for their potential to secrete
      phytohormones viz. gibberellins (GAs) and indoleacetic acid (IAA) and mitigate
      abiotic stresses like salinity and drought. The endophytic fungi Phoma glomerata
      LWL2 and Penicillium sp. LWL3 significantly promoted the shoot and allied growth
      attributes of GAs-deficient dwarf mutant Waito-C and Dongjin-beyo rice. Analysis
      of the pure cultures of these endophytic fungi showed biologically active GAs
      (GA1, GA3, GA4 and GA7) in various quantities. The cultures of P. glomerata and
      Penicillium sp. also contained IAA. The culture application and endophytic
      association with host-cucumber plants significantly increased the plant biomass
      and related growth parameters under sodium chloride and polyethylene glycol
      induced salinity and drought stress as compared to control plants. The endophytic
      symbiosis resulted in significantly higher assimilation of essential nutrients
      like potassium, calcium and magnesium as compared to control plants during
      salinity stress. Endophytic-association reduced the sodium toxicity and promoted
      the host-benefit ratio in cucumber plants as compared to non-inoculated control
      plants. The symbiotic-association mitigated stress by compromising the activities
      of reduced glutathione, catalase, peroxidase and polyphenol oxidase. Under stress
      conditions, the endophyte-infection significantly modulated stress through down
      regulated abscisic acid, altered jasmonic acid, and elevated salicylic acid
      contents as compared to control. In conclusion, the two endophytes significantly
      reprogrammed the growth of host plants during stress conditions.

PMID- 22960870
TI  - Aggregating behavior of phenolic compounds--a source of false bioassay results?
AB  - Previous descriptions of quercetin, a widely studied flavonoid, as a frequently
      reported nonspecific screening hit due to aggregating behavior has raised
      questions about the reliability of in vitro bioactivity reports of phenolic
      compounds. Here a systematic study on 117 phenolic compounds is presented,
      concerning their aggregating tendency and the relevance of this phenomenon to
      obtaining false bioassay results. Fourteen compounds formed aggregates detectable
      by dynamic light scattering (DLS) when assayed at 10 uM in Tris-HCl pH 7.5.
      Flavonoids were more prone to aggregation than other phenolic compounds, and the
      aggregate formation was highly dependent on the vehicle, ionic strength and pH.
      The compounds were also assayed against three unrelated enzymes in the presence
      and absence of Triton X-100, and their bioactivity ratios were collected from
      PubChem database. By comparing these datasets, quercetin and rhamnetin were
      confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher
      bioactivity ratios in the PubChem database than coumarins or organic acids. To
      conclude, aggregate formation can be controlled with Triton X-100 and this
      phenomenon needs to be considered when bioassay data is interpreted, but our data
      indicates that it does not always lead to unspecific inhibition of biological
      targets.

PMID- 22960871
TI  - Chiral separation and determination of excitatory amino acids in brain samples by
      CE-LIF using dual cyclodextrin system.
AB  - Chiral capillary electrophoresis method has been developed to separate aspartate
      and glutamate enantiomers to investigate the putative neuromodulator function of
      D-Asp in the central nervous system. To achieve appropriate detection sensitivity
      fluorescent derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole and laser
      induced fluorescence detection was applied. Although, simultaneous baseline
      separation of the two enantiomer pairs could be achieved by using 3 mM 6
      monodeoxy-6-mono(3-hydroxy)propylamino-beta-cyclodextrin (HPA-beta-CD), further
      improvement of the chemical selectivity was required because of the high excess
      of L-enantiomers in real samples to be analyzed. The system selectivity was fine
      tuned by combination of 8 mM heptakis(2,6-di-O-methyl)-beta-cyclodextrin and 5 mM
      HPA-beta-CD in order to increase the resolution between aspartate and glutamate
      enantiomers. The method was validated for biological application. The limits of
      detection for D-Asp and D-Glu were 17 and 9 nM, respectively, while the limit of
      quantification for both analytes was 50 nM. This is the lowest quantification
      limit reported so far for NBD-tagged D-Asp and D-Glu obtained by validated
      capillary electrophoresis laser-induced fluorescence method. The applicability of
      the method was demonstrated by analyzing brain samples of 1-day-old chickens. In
      all the studied brain areas, the D-enantiomer contributed 1-2 % of the total
      aspartate content, corresponding to 17-45 nmol/g wet tissue.

PMID- 22960872
TI  - Quantitation of intracellular purine intermediates in different Corynebacteria
      using electrospray LC-MS/MS.
AB  - Intermediates of the purine biosynthesis pathway play key roles in cellular
      metabolism including nucleic acid synthesis and signal mediation. In addition,
      they are also of major interest to the biotechnological industry as several
      intermediates either possess flavor-enhancing characteristics or are applied in
      medical therapy. In this study, we have developed an analytical method for
      quantitation of 12 intermediates from the purine biosynthesis pathway including
      important nucleotides and their corresponding nucleosides and nucleobases. The
      approach comprised a single-step acidic extraction/quenching procedure, followed
      by quantitative electrospray LC-MS/MS analysis. The assay was validated in terms
      of accuracy, precision, reproducibility, and applicability for complex biological
      matrices. The method was subsequently applied for determination of free
      intracellular pool sizes of purine biosynthetic pathway intermediates in the two
      Gram-positive bacteria Corynebacterium glutamicum and Corynebacterium
      ammoniagenes. Importantly, no ion pair reagents were applied in this approach as
      usually required for liquid chromatography analysis of large classes of diverse
      metabolites.

PMID- 22960873
TI  - An Italian battery for the assessment of semantic memory disorders.
AB  - We report the construction and standardization of a new comprehensive battery of
      tests for the assessment of semantic memory disorders. The battery is constructed
      on a common set of 48 stimuli, belonging to both living and non-living
      categories, rigidly controlled for several confounding variables, and is based on
      an empirically derived corpus of semantic features. It includes six tasks, in
      order to assess semantic memory through different modalities of input and output:
      two naming tasks, one with colored pictures and the other in response to an oral
      description, a word-picture matching task, a picture sorting task, a free
      generation of features task and a sentence verification task. Normative data on
      106 Italian subjects pooled across homogenous subgroups for age, sex and
      education are reported. The new battery allows an in-depth investigation of
      category-specific disorders and of progressive semantic memory deficits at
      features level, overcoming some of the limitations of existing tests.

PMID- 22960874
TI  - Restless legs syndrome in Iranian patients with multiple sclerosis.
AB  - Restless legs syndrome (RLS) is a common neurological movement disorder that is
      often seen in multiple sclerosis patients. However, the association between RLS
      and multiple sclerosis (MS) is still unclear and RLS is not considered as one of
      the MS symptoms. This study was conducted to assess the frequency of RLS and its
      associated factors in patients with MS. This was a cross-sectional study
      conducted during January and April 2010. A total of 205 patients diagnosed with
      multiple sclerosis (164 females, 41 males, mean age 32.8 +/- 8.9 years) were
      enrolled in the study and underwent a medical history interview and a
      neurological examination. The diagnosis of RLS was based on International
      Restless Legs Syndrome Study Group Criteria. 57 patients (27.8%) met the RLS
      diagnostic criteria. In 90.1% of the patients, the onset of RLS was simultaneous
      with or followed by MS onset. There was no significant difference between
      patients with and without RLS in respect of age, gender, disease duration, and MS
      pattern. There was an increased incidence of leg jerks before sleep in patients
      with RLS (P = 0.04). In patients suffering from RLS, there is greater complaint
      of insomnia (P = 0.03). Body mass index, history of anemia, excessive day-time
      somnolence, consuming caffeine-containing beverages, pregnancy numbers, smoking,
      and alcohol consumption were not associated with the presence of RLS. This study
      revealed high prevalence of RLS in MS patients. Screening of RLS in these
      patients should always be considered to improve management of MS.

PMID- 22960875
TI  - Ataxia-telangiectasia mutated (ATM) genetic variant in Italian centenarians.
AB  - Lifespan is attributable to genetic factors and some studies have attempted to
      identify putative genes implicated in human longevity. Several genetic loci have
      been associated with longevity, but some of these are not replicable, probably
      due to the vast differences among ethnicities. We analyzed in 128 Italian long
      lived individuals and 150 unrelated healthy subjects, the recently reported
      association between rs189037 in the ataxia-telangiectasia mutated gene promoter
      and longevity in Chinese nonagenarians/centenarians. Our study confirms the
      association between the rs189037 C/T genotype and longevity in Italian
      centenarians, with an odds ratio of 1.85 (95 % CI 0.99-3.45). To understand the
      genetic basis for longevity is an extraordinarily difficult task, and therefore
      it is important to replicate any positive findings, especially if detected in
      other ethnic groups, in order to reach reliable conclusions on the real effect
      that candidate genes have on longevity.

PMID- 22960876
TI  - Silk fibroin hydrolysate inhibits osteoclastogenesis and induces apoptosis of
      osteoclasts derived from RAW 264.7 cells.
AB  - Bone disease can be associated with bone resorption by osteoclasts, and interest
      in the development of antiresorptive agents has recently increased. The
      hydrolysate of silk fibroin has been studied with respect to such biomedical
      applications. In a previous study, silk fibroin showed indirect inhibitory
      effects on the differentiation of osteoclasts. To further evaluate the effect of
      a hydrolysate of silk fibroin on osteoclasts, we investigated the direct effects
      of the silk fibroin hydrolysate on osteoclastogenesis and apoptosis of
      osteoclasts induced by receptor activation of nuclear factor kappaB ligand
      (RANKL). The silk fibroin hydrolysate inhibited RANKL-induced formation of
      tartrate-resistant acid phosphatase (TRAP) in RAW 264.7 cells. The inhibitory
      effect of the silk fibroin hydrolysate resulted in the decreased expression of
      osteoclast marker genes, such as matrix metalloproteinase-9 (MMP-9), cathepsin-K
      and calcitonin receptor (CTR). In addition, the silk fibroin hydrolysate blocked
      the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear
      factor-kappaB (NF-kappaB) and expression of transcription factors, such as
      nuclear factor of activated T cells c1 (NFATc1) and NF-kappaB. Finally, the silk
      fibroin hydrolysate induced apoptosis signaling cascades. Taken together, the
      present results indicate that silk fibroin hydrolysate has antiresorptive
      activity by both inhibiting osteoclastogenesis and inducing osteoclast apoptosis.

PMID- 22960877
TI  - Successful eradication of a FVIII inhibitor in a 60-year-old patient with mild
      haemophilia A using single-agent prednisolone.
AB  - BACKGROUND: Development of FVIII inhibitors represents a major challenge in
      patients with mild haemophilia A (HA), because they tend to occur at an older age
      and classical immune tolerance induction appears to be less effective. CASE
      REPORT: A man (age: 60 years) with mild HA due to the missense mutation,
      Leu1929Arg, received a single dose of rFVIII at 35 IU/kg prior to routine
      colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was
      infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate,
      and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in
      FVIII:C of <1%. Two weeks later, the patient experienced spontaneous iliopsoas
      bleeding. Parallel to bypassing therapy, we started single-agent
      immunosuppression with prednisolone at 1.5mg/kg. FVIII:C "normalized" at 10.2%
      after four weeks. After five months, the inhibitor titre fell to <0.4 BU with
      sustained remission after one year of follow-up. CONCLUSION: In mild HA, FVIII
      inhibitors may share characteristic features with FVIII autoantibodies commonly
      observed in acquired HA. Therefore, immunosuppressive therapy alone could be
      successful at least in a subset of patients.

PMID- 22960878
TI  - Chitosan/poly(DL,lactide-co-glycolide) scaffolds for tissue engineering.
AB  - Chitosan/poly(DL-lactide-co-glycolide) (Ch/DL PLG) composite scaffolds were
      fabricated by freeze-drying lyophilization, and were evaluated and compared for
      use as a bone regeneration scaffold through measurements of the compression
      mechanical properties of the porous scaffolds. Also, In vitro cell culture of
      Sprague-Dawley rat's osteoblasts were used to evaluate the phenotype expression
      of cells in the scaffolds, characterizing the cellular adhesion, proliferation
      and alkaline phosphatase activity. The gene expression of osteocalcin,
      sialoprotein, alkaline phosphatase, Type I collagen and TGFbeta1 were confirmed
      in the samples; moreover, it was confirmed, the mineralization by IR spectra and
      EDS analysis. Our results thus show that Ch/DL PLG scaffolds are suitable for
      biological applications.

PMID- 22960879
TI  - Inaccuracy of age assessment from images of postpubescent subjects in cases of
      alleged child pornography.
AB  - Despite frequent medical expert testimony authoritatively stating that images of
      individuals who are postpubescent indicate age less than 18 and therefore, child
      pornography, developmental experts have noted that a scientific basis for such
      estimation is lacking. In fact, recent studies have demonstrated a high degree of
      inaccuracy in such estimates, and that the stage of breast development often used
      as indicative of age under 18 years is present in a substantial percentage of
      adult women. Ten images of adult women from legitimate pornographic sites
      promoting youthful images were shown to 16 pediatric endocrinologists expert in
      evaluating maturation, who determined whether or not the individuals represented
      were under 18 years of age. They also provided information about what features
      were most important in their evaluations. Sixty-nine percent of the 160 estimates
      were that the images represented females under 18 years of age. There was wide
      variability in the designation of importance of the various features of
      maturation in reaching conclusions, with breast development and facial appearance
      considered most important. This study confirms that medical testimony, even by
      experts in adolescent development, can deem images of adult women selected for
      their youthful appearance to be under age 18 two thirds of the time. Thus,
      important as prosecuting users of child pornographic material may be, justice
      requires the avoidance of testimony that is not scientifically based.

PMID- 22960880
TI  - Identification of forensically important Sarcophaga species (Diptera:
      Sarcophagidae) using the mitochondrial COI gene.
AB  - The identification of species of the forensically important genus Sarcophaga is
      very difficult and requires strong taxonomic expertise. In this study, we
      sequenced the mitochondrial cytochrome c oxidase subunit I (COI) gene of 126
      specimens of 56 W European Sarcophaga species and added GenBank data to our
      database to yield a total dataset of 270 COI sequences from 99 Sarcophaga species
      to evaluate the COI gene as a molecular diagnostic tool for species
      identification in this genus. Using two simple criteria (Best Match, BM and Best
      Close Match, BCM), we showed that the identification success using a mini-barcode
      region of 127 bp was very low (80.7-82.5 %) and the use of this region is not
      recommended as a species identifier. In contrast, identification success was very
      high using the standard barcode region (658 bp) or using the entire COI region
      (1,535 bp) (98.2-99.3 %). Yet, there was a low interspecific sequence divergence
      (<2 %) in six species groups so that for 16 out of the 99 species (nine of which
      are of forensic importance), the use of COI barcodes as species identifier should
      be done with care. For these species, additional markers will be necessary to
      achieve a 100 % identification success. We further illustrate how such reference
      databases can improve local reference databases for forensic entomologists.

PMID- 22960881
TI  - Development of the Chinese version of the Hooper Visual Organization Test: 
      normative data.
AB  - The present study consisted of two phases: development and psychometric
      validation of a Chinese version of the Hooper Visual Organization Test (HVOT)
      using Rasch analysis and the provision of normative data on the basis of a
      representative sample of the Chinese-speaking population. The HVOT was
      administered to 1008 healthy adults aged 15-79 years, 60 patients with stroke,
      and 60 patients with schizophrenia. The results indicated that with 12 items
      removed, the resulting 18-item scale was found to be unidimensional, with
      satisfactory internal consistency and no evidence of differential item
      functioning or bias for age, sex and educational level. There were significant
      differences between each of the two patient groups and normal controls on the
      scores of the Rasch-developed measure. All test-retest coefficients exceeded 90
      in patient samples. As performance on the Chinese version decreases with age and
      lower years of education, regression-based normative data that took age and
      education into account were established. A cut-off score of 21.5, out of an x-y
      range, the higher the better, resulted in a sensitivity of 0.86 and a specificity
      of 0.68. The normative data presented here will enable clinicians to determine
      different levels of visuosynthetic impairments more precisely.

PMID- 22960882
TI  - Juvenile diabetes.

PMID- 22960883
TI  - Information, education & communication: corner stone for preventing cancer of the
      cervix.

PMID- 22960884
TI  - The challenge of health & environment: profiling risks & strategic priorities for
      now & the future.
AB  - A substantial burden of communicable and non-communicable diseases in the
      developing countries is attributable to environmental risk factors. WHO estimates
      that the environmental factors are responsible for an estimated 24 per cent of
      the global burden of disease in terms of healthy life years lost and 23 per cent
      of all deaths; children being the worst sufferers. Given that the environment is
      linked with most of the Millennium Development Goals (MDGs), without proper
      attention to the environmental risk factors and their management, it will be
      difficult to achieve many MDGs by 2015. The impact of environmental degradation
      on health may continue well into the future and the situation in fact, is likely
      to get worse. In order to address this challenge, two facts are worth noting.
      First, that much of the environmental disease burden is attributable to a few
      critical risk factors which include unsafe water and sanitation, exposure to
      indoor smoke from cooking fuel, outdoor air pollution, exposure to chemicals such
      as arsenic, and climate change. Second, that environment and health aspects must
      become, as a matter of urgency, a national priority, both in terms of policy and
      resources allocation. To meet the challenge of health and environment now and in
      the future, the following strategic approaches must be considered which include
      conducting environmental and health impact assessments; strengthening national
      environmental health policy and infrastructure; fostering inter-sectoral co
      ordination and partnerships; mobilizing public participation; and enhancing the
      leadership role of health in advocacy, stewardship and capacity building.

PMID- 22960885
TI  - Paragonimus & paragonimiasis in India.
AB  - Ever since the discovery of the first indigenous case in 1981, paragonimiasis has
      gained recognition as a significant food borne parasitic zoonosis in India. The
      data available on the occurrence of paragonimiasis, until today, may be just the
      tip of an iceberg as the study areas covered were restricted to Northeast Indian
      States. Nevertheless, the results of research on paragonimiasis in India have
      revealed valuable information in epidemiology, life cycle, pathobiology and
      speciation of Indian Paragonimus. Potamiscus manipurensis, Alcomon superciliosum
      and Maydelliathelphusa lugubris were identified as the crab hosts of Paragonimus.
      Paragonimus miyazakii manipurinus n. sub sp., P. hueit'ungensis, P. skrjabini, P.
      heterotremus, P. compactus, and P. westermani have been described from India. P.
      heterotremus was found as the causative agent of human paragonimiasis. Ingestion
      of undercooked crabs and raw crab extract was the major mode of infection.
      Pulmonary paragonimiasis was the commonest clinical manifestation while pleural
      effusion and subcutaneous nodules were the common extra-pulmonary forms. Clinico
      radiological features of pulmonary paragonimiasis simulated pulmonary
      tuberculosis. Intradermal test, ELISA and Dot-immunogold filtration assay (DIGFA)
      were used for diagnosis and epidemiological survey of paragonimiasis.
      Phylogenitically, Indian Paragonimus species, although nested within the
      respective clade were distantly related to others within the clade.

PMID- 22960886
TI  - Cervical cancer screening: Current knowledge & practice among women in a rural
      population of Kerala, India.
AB  - BACKGROUND & OBJECTIVES: Cervical cancer has a major impact on woman's lives
      worldwide and one in every five women suffering from cervical cancer belongs to
      India. Hence the objectives of this study were to find the knowledge of women
      regarding cervical cancer, to determine screening practices and determinants, and
      to identify factors for non screening. METHODS: A cross-sectional study was
      conducted in Vypin Block of Ernakulam District, Kerala, India where four of the
      seven Panchayats were randomly chosen. Households were selected by systematic
      random sampling taking every second house in the tenth ward of the Panchayat till
      at least 200 women were interviewed. Thus, 809 women were interviewed from four
      Panchayats. RESULTS: Mean age of the study population was 34.5 + 9.23 yr. Three
      fourths of the population (74.2%) knew that cervical cancer could be detected
      early by a screening test. Majority of respondents (89.2%) did not know any risk
      factor for cervical cancer. Of the 809 women studied, only 6.9 per cent had
      undergone screening. One third of the population were desirous of undergoing
      screening test but had not done it due to various factors. These factors related
      to knowledge (51.4%) such as no symptoms, not being aware of Pap test, not
      necessary, etc. This was followed by resource factors (15.1%) like no time, no
      money, etc. and psychosocial factors (10.2%) included lack of interest, fear of
      procedure, etc. Independent predictors for doing Pap test included age >35,
      having knowledge of screening for cervical cancer and Pap test (P<0.05).
      INTERPRETATION & CONCLUSIONS: Specific knowledge on cervical cancer screening is
      a critical element in determining whether a woman will undergo Pap test in
      addition to making cancer screening facilities available in the primary health
      centre.

PMID- 22960887
TI  - Bone marrow cells contribute to tubular epithelium regeneration following acute
      kidney injury induced by mercuric chloride.
AB  - BACKGROUND & OBJECTIVES: Acute tubular necrosis (ATN) caused by renal ischaemia,
      renal hypo-perfusion, or nephrotoxic substances is the most common form of acute
      kidney injury (AKI). There are a few treatment options for this life-threatening
      disease and the mortality rate exceeds 50 per cent. In critical cases of AKI the
      only option is renal transplantation. In the present study we evaluated whether
      bone marrow cells (BMCs) are involved in regeneration of kidney tubules following
      acute tubular necrosis in the mouse. METHODS: Six to eight week old C57BL6/J and
      congenic enhanced green fluorescence protein (eGFP) mice were used. The relative
      contributions of eGFP-expressing BMCs were compared in two different approaches
      to kidney regeneration in the mercuric chloride (HgCl 2 )-induced mouse model of
      AKI: induced engraftment and forced engraftment. In vitro differentiation of
      lineage-depleted (Lin - ) BMCs into renal epithelial cells was also studied.
      RESULTS: In the forced engraftment approach, BMCs were found to play a role in
      the regeneration of tubules of renal cortex and outer medulla regions. About 70
      per cent of donor-derived cells expressed megalin. In vitro culture revealed that
      Lin - BMCs differentiated into megalin, E-cadherin and cytokeratin-19 (CK-19)
      expressing renal epithelial cells. INTERPRETATION & CONCLUSIONS: The present
      results demonstrate that Lin - BMCs may contribute in the regeneration of renal
      tubular epithelium of HgCl 2 -induced AKI. This study may also suggest a
      potential role of BMCs in treating AKI.

PMID- 22960888
TI  - Autologous intravenous bone marrow mononuclear cell therapy for patients with
      subacute ischaemic stroke: a pilot study.
AB  - BACKGROUND & OBJECTIVES: Bone marrow mononuclear cell therapy has emerged as one
      of the option for the treatment of Stroke. Several preclinical studies have shown
      that the treatment with mononuclear cell (MNCs) can reduce the infarct size and
      improve the functional outcome. We evaluated the feasibility, safety and clinical
      outcome of administering bone marrow mononuclear cell (MNCs) intravenously to
      patients with subacute ischaemic stroke. METHODS: In a non-randomized phase-I
      clinical study, 11 consecutive, eligible and consenting patients, aged 30-70 yr
      with ischaemic stroke involving anterior circulation within 7 to 30 days of onset
      of stroke were included. Bone marrow was aspirated from iliac crest and the
      harvested mononuclear cells were infused into antecubital vein. Outcomes measured
      for safety included immediate reactions after cell infusion and evidence of
      tumour formation at one year in whole body PET scan. Patients were followed at
      week 1, 4-6, 24 and 52 to determine clinical progress using National Institute of
      Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS),
      MRI, EEG and PET. Feasibility outcomes included target-dose feasibility.
      Favourable clinical outcome was defined as mRS score of 2 or less or BI score of
      75 to 100 at six months after stem cell therapy. RESULTS: Between September 2006
      and April 2007, 11 patients were infused with bone-marrow mononuclear cells (mean
      80 million with CD-34 + mean 0.92 million). Protocol was target-dose feasible in
      9 patients (82%). FDG-PET scan at 24 and 52 wk in nine patients did not reveal
      evidence of tumour formation. Seven patients had favourable clinical outcome.
      INTERPRETATION & CONCLUSIONS: Intravenous bone marrow mononuclear cell therapy
      appears feasible and safe in patients with subacute ischaemic stroke. Further, a
      randomized controlled trial to examine its efficacy is being conducted.

PMID- 22960889
TI  - Association of pro-inflammatory cytokines, adipokines & oxidative stress with
      insulin resistance & non-alcoholic fatty liver disease.
AB  - BACKGROUND & OBJECTIVES: The cytokines, adipokines, and oxidative stress have
      been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD);
      however, such data remain scarce in India. The present study evaluated pro
      inflammatory cytokines, adipokines, and markers of oxidative stress in patients
      with non-alcoholic fatty liver disease (NAFLD), and their association with degree
      of adiposity, insulin resistance and markers of disease severity. METHODS: The
      present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD,
      22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters
      studied were adiponectin, leptin, tumour necrosis factor alpha (TNFalpha),
      interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress.
      RESULTS: The mean body mass index (kg/m 2 ) in NAFLD patients, CHB, and HC were
      26.4+/-3.7, 21.3+/-2.3, and 22.3+/-2.7, respectively. The median serum levels of
      all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD
      compared to control groups. Compared to HC, levels of adiponectin and leptin were
      significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked
      and selective increase only in NAFLD patients. The levels of IL-6 were
      significantly (P<0.02) higher in NAFLD patients with advanced histology grade and
      correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress
      were significantly higher, and that of antioxidant potential were significantly
      lower among NAFLD patients compared to control subjects. INTERPRETATION &
      CONCLUSIONS: Patients with NAFLD revealed significantly elevated levels of pro
      inflammatory cytokines, increased oxidative stress, and a significant association
      of IL-6 with IR and advanced histopathology.

PMID- 22960890
TI  - AmpC beta-lactamases in nosocomial isolates of Klebsiella pneumoniae from India.
AB  - BACKGROUND & OBJECTIVES: AmpC beta-lactamases are clinically significant since
      these confer resistance to cephalosporins in the oxyimino group, 7-alpha
      methoxycephalosporins and are not affected by available beta-lactamase
      inhibitors. In this study we looked for both extended spectrum beta-lactamases
      (ESBL) and AmpC beta-lactamases in Klebsiella pneumoniae clinical isolates.
      METHODS: One hundred consecutive, non-duplicate clinical isolates of K.
      pneumoniae collected over a period of one year (June 2008 - June 2009) were
      included in the study. An antibiotic susceptibility method was used with 10
      antibiotics for Gram-negative infections which helped in screening for ESBL and
      AmpC beta-lactamases and also in confirmation of ESBL production. The detection
      of AmpC beta-lactamases was done based on screening and confirmatory tests. For
      screening, disc diffusion zones of cefoxitin <18 mm was taken as cefoxitin
      resistant. All cefoxitin resistant isolates were tested further by AmpC disk test
      and modified three dimensional test. Multiplex-PCR was performed for screening
      the presence of plasmid-mediated AmpC genes. RESULTS: Of the 100 isolates of K.
      pneumoniae studied, 48 were resistant to cefoxitin on screening. AmpC disk test
      was positive in 32 (32%) isolates. This was also confirmed with modified three
      dimensional test. Indentation indicating strong AmpC producer was observed in 25
      isolates whereas little distortion (weak AmpC) was observed in 7 isolates. ESBL
      detection was confirmed by a modification of double disk synergy test in 56
      isolates. Cefepime was the best cephalosporin in synergy with tazobactam for
      detecting ESBL production in isolates co-producing AmpC beta-lactamases. The
      subsets of isolates phenotypically AmpC beta-lactamase positive were subjected to
      amplification of six different families of AmpC gene using multiplex PCR. The
      sequence analysis revealed 12 CMY-2 and eight DHA-1 types. INTERPRETATION &
      CONCLUSIONS: Tazobactam was the best beta-lactamase inhibitor for detecting ESBL
      in presence of AmpC beta-lactamase as this is a very poor inducer of AmpC gene.
      Amongst cephalosporins, cefepime was the best cephalosporin in detecting ESBL in
      presence of AmpC beta-lactamase as it is least hydrolyzed by AmpC enzymes.
      Cefepime-tazobactam combination disk test would be a simple and best method in
      detection of ESBLs in Enterobacteriaceae co-producing AmpC beta-lactamase in the
      routine diagnostic microbiology laboratories.

PMID- 22960891
TI  - Weight homeostasis & its modulators in hyperthyroidism before & after treatment
      with carbimazole.
AB  - BACKGROUND & OBJECTIVES: Hyperthyroidism is associated with increased food
      intake, energy expenditure and altered body composition. This study was aimed to
      evaluate the role of adipocytokines in weight homeostasis in patients with
      hyperthyroidism. METHODS: Patients (n=27, 11men) with hyperthyroidism (20 Graves'
      disease, 7 toxic multinodular goiter) with mean age of 31.3+/-4.2 yr and 28
      healthy age and body mass index (BMI) matched controls were studied. They
      underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual
      energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state
      for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids.
      Patients were re-evaluated after 3 months of treatment as by that time all of
      them achieved euthyroid state with carbimazole therapy. RESULTS: The LBM was
      higher (P<0.001) in healthy controls as compared to hyperthyroid patients even
      after adjustment for body weight (BW), whereas total body fat was comparable
      between the two groups. Serum leptin levels were higher in patients with
      hyperthyroidism than controls (22.3+/-3.7 and 4.1+/-0.34 ng/ml, P<0.001), whereas
      adiponectin levels were comparable. Plasma acylated ghrelin was higher in
      patients than in controls (209.8+/-13.3 vs 106.2+/-8.2 pg/ml, P<0.05).
      Achievement of euthyroidism was associated with significant weight gain (P<0.001)
      and significant increase in lean body mass (P<0.001). The total body fat also
      increased but insignificantly from 18.4+/-1.8 to 19.9+/-1.8 kg. There was
      significant decrease (P<0.05) in serum leptin and acylated ghrelin but
      adiponectin levels remained unaltered after treatment. Serum leptin positively
      correlated with TBF and this correlation persisted even after adjustment for BW,
      BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin
      did not correlate with the presence or absence of hyperphagia. INTERPRETATION &
      CONCLUSION: Patients with hyperthyroidism predominantly had decreased lean body
      mass which increased after achievement of euthyroidism with carbimazole. The
      hyperphagia and the alterations in weight homeostasis associated with
      hyperthyroidism were independent of circulating leptin and ghrelin levels.

PMID- 22960892
TI  - Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups
      from Malaysia.
AB  - BACKGROUND & OBJECTIVES: Genetic polymorphisms of uridine diphosphate
      glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of
      responses among patients prescribed with irinotecan. Lack of this enzyme is known
      to be associated with a high incidence of severe toxicity. The objective of this
      study was to investigate the prevalence of three different variants of UGT1A1
      (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme
      activity and increased irinotecan toxicity, in the three main ethnic groups in
      Malaysia (Malays, Chinese and Indians). METHODS: A total of 306 healthy unrelated
      volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5
      ml) were obtained from each subject and DNA was extracted. PCR based methods were
      designed and validated for detection of UGT1A1*, UUGT1A1*27 and UUGT1A1*28.
      Direct DNA sequencing was performed to validate the results of randomly selected
      samples. RESULTS: Malays and Indian have two-fold higher frequency of homozygous
      of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the
      Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no
      significant differences among them. UGT1A1*27 which has not been detected in
      Caucasian and African American population, was found in the Malaysian Malays
      (3.33%) and Malaysian Chinese (2.0%). INTERPRETATION & CONCLUSIONS: There was
      interethnic variability in the frequency of UGT1A1*28 in the Malaysian
      population. Our results suggest that genotyping of UUGT1A1*6, UGT1A1*28 and
      UGT1A1*27 need to be performed before patients are prescribed with irinotecan due
      to their high prevalence of allelic variant which could lead to adverse drug
      reaction.

PMID- 22960893
TI  - Isolation of a variant human adenovirus identified based on phylogenetic analysis
      during an outbreak of acute keratoconjunctivitis in Chennai.
AB  - BACKGROUND & OBJECTIVES: Though several viruses are responsible for
      conjunctivitis, but human adenovirus (HAdV) is by far the most common cause.
      Epidemic conjunctivitis causes morbidity and early detection of aetiological
      agent is essential in preventing spread of disease as some of serotypes of
      adenoviruses cause a severe form of conjunctivitis. This study was undertaken to
      identify the causative agent of conjunctivitis outbreak in Chennai in 2010.
      METHODS: Conjunctival samples collected from 17 patients with conjunctivitis were
      subjected to virological investigations. Culture and PCR for detection of
      adenovirus and enterovirus were carried out. PCR positive products were further
      subjected for DNA sequencing. The nucleotide sequences of the hexons of isolates
      were analyzed by comparison with all 51 human adenovirus strains. Phylogenetic
      tree was constructed using DAMBE software. RESULTS: Among 17 patients, seven were
      positive for adenovirus by PCR on the direct specimen, none was positive for
      enterovirus. Eleven of 30 conjunctival swabs showed cytopathic effect in HEp-2
      cell line and were confirmed as HAdV by PCR. The DNA sequence data of the 11
      isolates had equal percentage of homology with HAdV 6 and 2 on blast analysis. On
      phylogenetic analysis with GeneBank data of 51 adenovirus strains, 11 isolates
      from patients during the outbreak of conjunctivitis formed a separate clade
      indicating a new variant strain. INTERPRETATION & CONCLUSIONS: Based on
      phylogenetic analysis it was concluded that the recent conjunctivitis outbreak
      that occurred in Chennai was caused by a variant adenovirus strain.

PMID- 22960894
TI  - Visual inspection of cervix with Lugol's iodine for early detection of
      premalignant & malignant lesions of cervix.
AB  - BACKGROUND & OBJECTIVES: Majority of cases of cervical cancer are diagnosed at an
      advanced stage as cytology based screening programmes are ineffective in
      developing countries. The present study was done to look for carcinoma cervix and
      its precursors by visual inspection with Lugol's iodine (VILI), visual inspection
      with acetic acid (VIA) and Papanicolaou smear, and to analyse their sensitivity,
      specificity and predictive values using colposcopic directed biopsy as reference.
      METHODS: In this cross-sectional study, 350 women were subjected to Pap smear,
      VIA, VILI and colposcopy. Cervical biopsy and endocervical curettage was taken
      from patients positive on any of these tests and in 10 per cent of negative
      cases. RESULTS: The Pap smear was abnormal in 3.71 per cent, including (2.85%),
      low grade (LSIL) and (0.85%) high grade squamous intraepithelial lesions (HSIL).
      Thirteen per cent of the patients were found to be positive by VIA and 11.71 per
      cent were positive on VILI. Sensitivity for VIA, VILI and Pap smear was 89.5, 100
      and 52.6 per cent, respectively, while the specificity for VIA, VILI and Pap
      smear was 91.2, 93.3 and 99.1 per cent, respectively. INTERPRETATION &
      CONCLUSIONS: In low resource settings, cervical cancer screening by Pap smear can
      be replaced by visual methods like VILI, which has the highest sensitivity (100%)
      to detect any grade of dysplasia, and a good specificity (93.3%).

PMID- 22960895
TI  - The effect of warm liver ischaemia & reperfusion injury on circulating plasma
      lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic
      preconditioning.
AB  - BACKGROUND & OBJECTIVES: Ischaemia/reperfusion (I/R) associated with major liver
      surgery compromises liver function. Ischaemic preconditioning (IPC) may be
      effective in minimizing hepatic I/R injury. This study aimed to investigate the
      impact of liver ischaemic manipulations on lipid metabolism in rat during the
      process of liver recovery after liver surgery. METHODS: Sixty three male Wistar
      rats were assigned to three groups: the sham group, the I/R group which underwent
      warm ischaemia and reperfusion (I/R), and the IPC group. The animals were
      subdivided in 3 groups [1 st , 3 rd and 7 th postoperative day (PO)]. Hepatic
      lipase (HL) and total lipase (TL) activity and the levels of aspartate and
      alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were
      measured in plasma. RESULTS: There was no significant difference in the activity
      of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were
      observed in the IPC group when compared to the other groups on the 3 rd PO day.
      Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the
      sham group on the 7 th PO day while HDL was also higher in the I/R group.
      Significantly higher cholesterol levels were found in the I/R and IPC groups on
      the 7 th PO day, which were not observed in the sham group. There was a similar
      curve for triglycerides in the sham and IPC groups while there were significantly
      higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in
      the IPC group were higher on the 3 rd and 7 th PO day, compared to day 1.
      INTERPRETATION & CONCLUSION: Warm ischaemia and I/R injury do not seem to affect
      lipolytic enzyme activity after the 1 st PO day despite the effects on plasma
      lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in
      plasma.

PMID- 22960896
TI  - Cross-cultural standardization of the South Texas Assessment of Neurocognition in
      India.
AB  - BACKGROUND & OBJECTIVES: Despite the central role of cognition for mental
      disorders most studies have been conducted in western countries. Similar research
      from other parts of the world, particularly India, is very limited. As a first
      step in closing this gap this cross-cultural comparability study of the South
      Texas Assessment of Neurocognition (STAN) battery was conducted between USA and
      India. METHODS: One hundred healthy adults from Kerala, India, were administered
      six language independent subtests of the Java Neuropsychological Test (JANET)
      version of the STAN, assessing aspects of general intellectual ability (Matrix
      Reasoning), attention (Identical Pairs Continuous Performance, 3 Symbol Version
      Test; IPCPTS), working memory (Spatial Capacity Delayed Response Test; SCAP),
      response inhibition (Stop Signal Reaction Time; SSRT), Emotional Recognition and
      Risk taking (Balloon Analogue Risk Task; BART). Test results were compared to a
      demographically matched US sample. RESULTS: Overall test performance in the
      Kerala sample was comparable to that of the US sample and commensurate to that
      generally described in studies from western countries. INTERPRETATION &
      CONCLUSIONS: Our results support the metric equivalence of currently available
      cognitive test batteries developed in western countries for use in India.
      However, the sample was restricted to individuals who were literate and had
      completed basic primary and secondary education.

PMID- 22960897
TI  - High occurrence of blaCMY-1 AmpC lactamase producing Escherichia coli in cases of
      complicated urinary tract infection (UTI) from a tertiary health care centre in
      north India.
AB  - AmpC beta lactamase producing Gram-negative bacteria have emerged worldwide. It
      is important to distinguish plasmid mediated AmpC beta lactamases from
      chromosomally mediated enzymes for surveillance, epidemiology and hospital
      infection control as plasmid mediated genes can spread to other organisms.
      Occurrence of blaCMY-1 AmpC beta-lactamase, a plasmid mediated cephamycinase was
      studied in 100 consecutive isolates of Escherichia coli from cases of complicated
      urinary tract infection (UTI). Screening for AmpC production was done by modified
      Hodge test, three dimensional test and AmpC disk test. All isolates showing a
      positive result by 2 out of 3 tests were then tested for blaCMY-1 gene by PCR.
      Fifty nine isolates were positive for AmpC beta lactamase production, 56.6 per
      cent were positive by PCR. Eight out of 13 isolates which were negative by EDTA
      disk method were positive by PCR, whereas none of the isolates negative by 3D and
      modified Hodge test was positive by PCR. Among admitted patients urinary
      catheterisation was the major risk factor followed by obstructive uropathy, three
      patients developed urosepsis. High occurrence of blaCMY-1 AmpC beta-lactamase
      warrants health care workers to endorse good hospital practices.

PMID- 22960898
TI  - Genetic polymorphism in Plasmodium falciparum: differentiation of parasite
      isolates of high & low virulence by RAPD.
AB  - BACKGROUND & OBJECTIVES: The increase in Plasmodium falciparum infections which
      are associated with severe and complicated malaria and drug resistance has made
      control of malaria a difficult task. Extensive genetic polymorphism in P.
      falciparum has been reported from several parts of the world which affects the
      efficacy of sub-unit vaccines. The knowledge of genotypes of the parasite in a
      geographical region is therefore, important for effective management and control.
      The aim of the present study was to investigate the usefulness of random
      amplified polymorphic DNA (RAPD)-PCR technique for differentiation of P.
      falciparum isolates from patients presenting with severe (cerebral malaria) and
      mild malaria. METHODS: Genetic polymorphism in 21 P. falciparum isolates obtained
      from patients found positive for P. falciparum by light microscopy was studied by
      RAPD-PCR analysis. Eleven RAPD primers were used for analysis of 21 P. falciparum
      isolates obtained from cerebral and non-cerebral malaria patients. RESULTS: Of
      the 11 primers, only three (E-4, E-8, and R-8) produced useful polymorphic
      patterns. The cluster analysis based on UPGMA demonstrated that isolates causing
      cerebral malaria cluster separately from those causing uncomplicated malaria.
      However, the analysis of phylogenic tree showed that P. falciparum isolates
      causing non-cerebral and cerebral malaria clustered separately but showed
      relatedness. INTERPRETATION & CONCLUSIONS: The results of the present study
      showed that the RAPD-PCR was able to differentiate the isolates causing severe
      and mild malaria. The cluster analysis of the phylogenic tree suggested that the
      virulent strains evolved from less virulent strains as it clustered separately.
      RAPD technique may be useful in discriminating between the different isolates of
      the same species resulting in different clinical profiles.

PMID- 22960900
TI  - Public health & GIS: Views & opinions of Indian users.

PMID- 22960899
TI  - Unexplained early pregnancy loss: role of paternal DNA.

PMID- 22960901
TI  - Outdoor physical activity & cardiovascular health.

PMID- 22960902
TI  - Aetiological agents of community acquired pneumonia.

PMID- 22960903
TI  - HCV genotypes distribution pattern in India.

PMID- 22960904
TI  - Changes in markers of bone turnover during treatment of hyperthyroidism.

PMID- 22960905
TI  - Vitamin D deficiency in hyperthyroidism.

PMID- 22960906
TI  - An unusual cause of superior vena cava syndrome.

PMID- 22960907
TI  - Bio-hybrid muscle cell-based actuators.
AB  - Actuation is an essential function of any artificial or living machine, allowing
      its movement and its interaction with the surrounding environment. Living muscles
      have evolved over millions of years within animals as nature's premier living
      generators of force, work and power, showing unique characteristics in comparison
      with standard artificial actuators. Current actuation technologies actually
      represent a real bottleneck in many robotics and ICT applications, including the
      bio-inspired ones. Main limitations involve inertia and backdrivability,
      stiffness control and power consumption. The development of novel actuators able
      to better mimic or even to overcome living muscle performances would open new
      horizons in robotics and ICT technologies: these components would allow the raise
      of a new generation of machines, with life-like movements and outstanding
      performances. An innovative solution to achieve this goal is represented by the
      merging between artificial and living entities, towards the realization of bio
      hybrid devices. The aim of the present article is to describe the scientific and
      technological efforts made by researchers in the last two decades to achieve cell
      or tissue-based actuators, with the dream of matching or outperforming natural
      muscles and to efficiently power micro- and mini-devices. The main challenges
      connected to the development of a cell-based actuator are highlighted and the
      most recent solutions to this scientific/technological problem are depicted,
      reporting advantages and drawbacks of each single approach. Future perspectives
      are also described, envisioning bio-hybrid actuators as key components of a new
      generation of machines able to show life-like movements and behaviors.

PMID- 22960908
TI  - Capping protein modulates the dynamic behavior of actin filaments in response to
      phosphatidic acid in Arabidopsis.
AB  - Remodeling of actin filament arrays in response to biotic and abiotic stimuli is
      thought to require precise control over the generation and availability of
      filament ends. Heterodimeric capping protein (CP) is an abundant filament capper,
      and its activity is inhibited by membrane signaling phospholipids in vitro. How
      exactly CP modulates the properties of filament ends in cells and whether its
      activity is coordinated by phospholipids in vivo is not well understood. By
      observing directly the dynamic behavior of individual filament ends in the
      cortical array of living Arabidopsis thaliana epidermal cells, we dissected the
      contribution of CP to actin organization and dynamics in response to the
      signaling phospholipid, phosphatidic acid (PA). Here, we examined three cp
      knockdown mutants and found that reduced CP levels resulted in more dynamic
      activity at filament ends, and this significantly enhanced filament-filament
      annealing and filament elongation from free ends. The cp mutants also exhibited
      more dense actin filament arrays. Treatment of wild-type cells with exogenous PA
      phenocopied the actin-based defects in cp mutants, with an increase in the
      density of filament arrays and enhanced annealing frequency. These cytoskeletal
      responses to exogenous PA were completely abrogated in cp mutants. Our data
      provide compelling genetic evidence that the end-capping activity of CP is
      inhibited by membrane signaling lipids in eukaryotic cells. Specifically, CP acts
      as a PA biosensor and key transducer of fluxes in membrane signaling
      phospholipids into changes in actin cytoskeleton dynamics.

PMID- 22960909
TI  - Novel plant immune-priming compounds identified via high-throughput chemical
      screening target salicylic acid glucosyltransferases in Arabidopsis.
AB  - Plant activators are compounds, such as analogs of the defense hormone salicylic
      acid (SA), that protect plants from pathogens by activating the plant immune
      system. Although some plant activators have been widely used in agriculture, the
      molecular mechanisms of immune induction are largely unknown. Using a newly
      established high-throughput screening procedure that screens for compounds that
      specifically potentiate pathogen-activated cell death in Arabidopsis thaliana
      cultured suspension cells, we identified five compounds that prime the immune
      response. These compounds enhanced disease resistance against pathogenic
      Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the
      accumulation of endogenous SA, but reduced its metabolite, SA-O-beta-d-glucoside.
      Inducing compounds inhibited two SA glucosyltransferases (SAGTs) in vitro. Double
      knockout plants that lack both SAGTs consistently exhibited enhanced disease
      resistance. Our results demonstrate that manipulation of the active free SA pool
      via SA-inactivating enzymes can be a useful strategy for fortifying plant disease
      resistance and may identify useful crop protectants.

PMID- 22960910
TI  - Overexpression of Arabidopsis plasmodesmata germin-like proteins disrupts root
      growth and development.
AB  - In plants, a population of non-cell-autonomous proteins (NCAPs), including
      numerous transcription factors, move cell to cell through plasmodesmata (PD). In
      many cases, the intercellular trafficking of these NCAPs is regulated by their
      interaction with specific PD components. To gain further insight into the
      functions of this NCAP pathway, coimmunoprecipitation experiments were performed
      on a tobacco (Nicotiana tabacum) plasmodesmal-enriched cell wall protein
      preparation using as bait the NCAP, pumpkin (Cucurbita maxima) PHLOEM PROTEIN16
      (Cm-PP16). A Cm-PP16 interaction partner, Nt-PLASMODESMAL GERMIN-LIKE PROTEIN1
      (Nt-PDGLP1) was identified and shown to be a PD-located component. Arabidopsis
      thaliana putative orthologs, PDGLP1 and PDGLP2, were identified; expression
      studies indicated that, postgermination, these proteins were preferentially
      expressed in the root system. The PDGLP1 signal peptide was shown to function in
      localization to the PD by a novel mechanism involving the endoplasmic reticulum
      Golgi secretory pathway. Overexpression of various tagged versions altered root
      meristem function, leading to reduced primary root but enhanced lateral root
      growth. This effect on root growth was corrected with an inability of these
      chimeric proteins to form stable PD-localized complexes. PDGLP1 and PDGLP2 appear
      to be involved in regulating primary root growth by controlling phloem-mediated
      allocation of resources between the primary and lateral root meristems.

PMID- 22960912
TI  - A case of insanity: diagnostic relevance in the shadow of Columbine.

PMID- 22960913
TI  - Postpartum psychosis and the courts.
AB  - Although mental state defenses frequently are raised in cases of infanticide,
      legal criteria for these defenses vary across jurisdictions. We reviewed outcomes
      of such cases in states using M'Naughten or model penal code (MPC) standards for
      insanity, and the factors considered by the courts in reaching these decisions.
      LexisNexis and Westlaw searches were conducted of case law, legal precedent, and
      law review articles related to infanticide. Google and other Internet search
      engines were used to identify unpublished cases. Despite the differing legal
      standards for insanity among states, the outcomes of infanticide cases do not
      appear to be dependent solely on which standard is used. The presence of
      psychosis was important in the successful mental state defenses. This case series
      suggests that states that use the stricter M'Naughten standard have not been less
      likely than states with an MPC standard to adjudicate women who have committed
      infanticide as not guilty by reason of insanity.

PMID- 22960911
TI  - IAA-Ala Resistant3, an evolutionarily conserved target of miR167, mediates
      Arabidopsis root architecture changes during high osmotic stress.
AB  - The functions of microRNAs and their target mRNAs in Arabidopsis thaliana
      development have been widely documented; however, roles of stress-responsive
      microRNAs and their targets are not as well understood. Using small RNA deep
      sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala
      Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved
      at the miR167a complementary site and under high osmotic stress miR167a levels
      decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form
      of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA),
      a central phytohormone for root development. In contrast with the wild type, iar3
      mutants accumulated reduced IAA levels and did not display high osmotic stress
      induced root architecture changes. Transgenic plants expressing a cleavage
      resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed
      increased lateral root development compared with transgenic plants expressing
      wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by
      target mimicry led to an increase in IAR3 mRNA levels, further confirming the
      inverse relationship between the two partners. Sequence comparison revealed the
      miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant
      species. Finally, we showed that IAR3 is required for drought tolerance.

PMID- 22960914
TI  - Commentary: postpartum psychosis, infanticide, and insanity--implications for
      forensic psychiatry.
AB  - Two dozen nations have infanticide laws that decrease the penalty for mothers who
      kill their children of up to one year of age. The United States does not have
      such a law, but mentally ill mothers may plead not guilty by reason of insanity.
      As in other crimes, in addition to the diagnosis of a mental disorder, other
      factors, such as knowledge of wrongfulness and motive, are critical to the
      assessment. Postpartum psychosis has been described for 2,000 years and modern
      science supports a genetic component to the risk. Yet, the Diagnostic and
      Statistical Manual of Mental Disorders does not include it as a diagnosis,
      leading to difficulty in testimony. In this article, we discuss postpartum
      psychosis, infanticide law, and research regarding mothers who kill, and we make
      recommendations to forensic psychiatrists.

PMID- 22960915
TI  - Transferring juvenile defendants from adult to juvenile court: how Maryland
      forensic evaluators and judges reach their decisions.
AB  - The purpose of the study was to determine how often Maryland judges agreed with
      the opinions of forensic evaluators in deciding whether to transfer youthful
      defendants to juvenile court from adult court and to investigate which factors
      were most important in the opinions of the evaluators and the final decisions of
      the judges. Data were extracted from a sample of 200 waiver evaluations, and case
      outcomes were determined. Factors were examined with both univariate analysis and
      logistic regression models, to find correlates to and predictors of judges'
      decisions and evaluators' opinions. The most important factor influencing the
      decision of the judges was the forensic evaluators' opinions. Logistic regression
      analysis identified three factors that were significant predictors of the
      evaluator's opinion: public safety risk, history of the involvement of Department
      of Juvenile Services, and defendant's age at the time of the offense. The judges'
      decisions correlated strongly with the forensic evaluators' opinions.

PMID- 22960916
TI  - Commentary: nuances of reverse-waiver evaluations of adolescents in adult
      criminal court.
AB  - Several factors influence a judge's decision to transfer youthful defendants to
      juvenile court from adult court, including the forensic evaluator's ultimate
      opinion, the defendant's amenability to treatment, and public safety risk. In
      this commentary, we examine the constructs that evaluators must assess, as
      established by Kent v. United States (1966). We begin by outlining the legal
      history that led to the large population of youths currently in the adult
      criminal justice system nationwide and the negative consequences of their
      incarceration in adult settings. We consider the unique role of forensic
      psychologists and psychiatrists as experts in development, with special regard to
      their ability to assess and inform the court about amenability to treatment and
      emotional maturity. The determination of amenability to treatment is further
      explored through a review of the current literature examining the influence of
      diagnostic labeling on judicial decisions and the treatment response of
      adolescent offenders who have psychopathy features. We conclude with an update on
      the recent proposal for juvenile justice reform in the authors' state of New
      York.

PMID- 22960918
TI  - Firesetting, arson, pyromania, and the forensic mental health expert.
AB  - Firesetting is a common behavior that is frequently encountered by forensic
      mental health experts when consulting on criminal and civil legal cases. Despite
      its prevalence, minimal attention has been paid in the literature to conducting
      firesetting-related forensic evaluations. In this article, we discuss the
      differences in the behavior of firesetting, the crime of arson, and the diagnosis
      of pyromania. The literature on adult firesetter characteristics, classification
      systems, recidivism, and treatment is reviewed. Several types of common criminal
      and civil firesetting-related evaluations referred to forensic mental health
      experts are discussed, along with case examples illustrating how the courts have
      approached such assessments. To our knowledge, this article is the first in 20
      years to address firesetting-related forensic evaluations within the psychiatry
      literature. It also represents the first comprehensive discussion of civil
      evaluations related to firesetting.

PMID- 22960917
TI  - Risk of death for veterans on release from prison.
AB  - We sought to determine, among veterans released from Washington state prisons
      from 1999 through 2003, the risk of death from all causes, whether those veterans
      have faced a higher risk of death than have nonveterans, and whether having VA
      benefits decreased the risk of death. We linked data from a retrospective cohort
      study to data from the Veterans Benefit Administration. Mortality rates were
      compared between veteran and nonveteran former inmates. The crude rate of veteran
      mortality was 1,195 per 100,000 person-years, significantly higher than that of
      nonveterans (p < .001), but adjustment for demographic factors demonstrated no
      significant increased risk. VA benefits were associated with a reduced risk for
      all-cause deaths (hazard ratio, .376; 95% confidence interval, 0.18-0.79).
      Veterans share the heightened risk of death after release from prison faced by
      all released inmates and should be included in efforts to reduce the risks
      associated with transitioning from prison to the community. VA benefits appear to
      offer a protective effect, particularly against medical deaths.

PMID- 22960919
TI  - A training program for defendants with intellectual disabilities who are found
      incompetent to stand trial.
AB  - In this study, we examined whether a specialized training program, the Slater
      Method, affects rates at which persons with intellectual disabilities attain
      competence to stand trial. We reviewed records of all 30 persons with Diagnostic
      and Statistical Manual of Mental Disorders (DSM-IV-TR) clinical diagnoses of
      mental retardation (in this article, intellectual disability) or borderline
      intellectual functioning whom courts sent to Eleanor Slater Hospital for
      competency restoration from 2001 through 2006. Significantly more persons exposed
      to the Slater Method attained clinical trial competence (61.1%) than did persons
      who received traditional treatment alone (16.7%). Discussion focuses on potential
      limitations of the study, ethics-related concerns regarding use of the Slater
      Method, and directions for future research.

PMID- 22960920
TI  - Brief Rating of Aggression by Children and Adolescents (BRACHA): a reliability
      study.
AB  - The Brief Rating of Aggression by Children and Adolescents (BRACHA) is a 14-item
      instrument scored by emergency room staff members to assess aggression risk
      during an upcoming psychiatric hospitalization. In this study, we investigated
      the inter-rater reliability of the BRACHA 0.9, the latest version of the
      instrument. After receiving training based on the BRACHA 0.9 manual, 10 intake
      workers viewed 24 ten-minute videos in which child and adolescent actors
      portrayed pediatric emergency room patients with low, moderate, or high levels of
      risk for aggression during an upcoming hospitalization. We then evaluated inter
      rater reliability for individual BRACHA items, using three measures of agreement,
      and reliability for total BRACHA 0.9 scores, using conventional (frequentist)
      methods and Bayesian techniques for calculating the intraclass correlation
      coefficient ICC (2,1). Inter-rater reliability for individual items ranged from
      good to almost perfect, with Kendall's W exceeding 0.75 for eight of 14 BRACHA
      items. The ICC (2,1) for the total BRACHA 0.9 score was 0.9099, with both
      conventional and Bayesian methods (95% credible interval 0.8530-0.9533),
      suggesting an excellent level of overall agreement. The BRACHA appears to be an
      accurate, highly reliable instrument for assessing the risk of aggression by
      children and adolescents who are about to undergo psychiatric hospitalization.

PMID- 22960921
TI  - CRIPA, Olmstead, and the transformation of the Oregon Psychiatric Security Review
      Board.
AB  - This commentary explores the relationship among the 1999 U.S. Supreme Court
      Olmstead decision; the Department of Justice, Civil Rights Division, in its
      application of CRIPA (the Civil Rights of Institutionalized Patients Act); and
      the application of both CRIPA and Olmstead to the question of individuals
      hospitalized in state mental institutions following commitment from criminal
      courts. Using Oregon as an example, the commentary illustrates the interplay
      between state and federal governments as Olmstead and CRIPA are expanded into the
      realm of criminal court commitments to state facilities and into the arena of
      community mental health services for deinstitutionalized persons.

PMID- 22960922
TI  - Compensation neurosis: a too quickly forgotten concept?
AB  - There has been great debate concerning the existence and meaning of compensation
      neurosis. It is included in the International Classification of Diseases (ICD)-9
      and -10 but not listed in the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV-TR). On the eve of publication
      of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM
      5), we re-examine the history and concept of compensation neurosis and
      conceptually update the condition to reflect current psychiatric thought. We
      consider its utility as a diagnostic entity for forensic evaluations and its
      components as they relate to exaggeration in injury claims. We also discuss how
      compensation neurosis differs from malingering and factitious disorder.

PMID- 22960923
TI  - Firearms inquiries in Florida: "medical privacy" or medical neglect?
AB  - A recent Florida law, Medical Privacy Concerning Firearms, potentially bars
      physicians from being able to ask patients about firearms ownership unless safety
      is an immediate concern. The ability of physicians to provide preventive medicine
      and perform risk assessments could be threatened. The ensuing debate has focused
      on a political and constitutional battleground between physicians and patients.
      In this article, we analyze the arguments from both perspectives and offer
      suggestions to physicians facing this unique clinical dilemma.

PMID- 22960924
TI  - Sexual sadism: avoiding its misuse in sexually violent predator evaluations.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),
      Task Force has recently rejected the proposal to include coercive paraphilia as
      an official diagnosis, reaffirming that rape is a crime and not a mental
      disorder. We hope this will discourage what has been the inappropriate practice
      of giving rapists the made-up diagnosis of paraphilia, NOS, nonconsent, to
      facilitate their psychiatric commitment under sexually violent predator (SVP)
      statutes. Losing the paraphilia, NOS, option has tempted some SVP evaluators to
      overdiagnose sexual sadism, which is an official DSM mental disorder. To prevent
      this improper application and to clarify those rare instances in which this
      diagnosis might apply, we present a brief review of the research on sexual
      sadism; an annotation of its definitions that have been included in the DSM since
      the Third Edition, published in 1980, and in the International Classification of
      Diseases, Tenth Edition (ICD-10); and a two-step process for making a diagnostic
      decision. Rape and sexual sadism have in common violence, cruelty, and a callous
      indifference on the part of the perpetrator to the suffering of the victim, but
      they differ markedly in motivation. Rapists use violence to enforce the victim's
      cooperation, to express aggression, or both. In contrast, in sexual sadism, the
      violence, domination, and infliction of pain and humiliation are a preferred or
      necessary precondition for sexual arousal. Only a small proportion of rapists
      qualify for the diagnosis of sexual sadism.

PMID- 22960926
TI  - Emerging perspectives on adolescents and young adults with high-functioning
      autism spectrum disorders, violence, and criminal law. Correction.

PMID- 22960925
TI  - A model treatment refusal procedure for defendants found incompetent to stand
      trial in the ninth circuit.
AB  - Pretrial detainees have a constitutionally protected right to refuse medical
      treatment in most circumstances; however, individuals found incompetent to stand
      trial (IST) due to a mental disorder can be treated involuntarily by clinicians
      who adhere to careful medical and legal procedures. The process of involuntary
      treatment of IST pretrial detainees begins with categorization into particular
      legal and medical groups. These different categories affect the individual's
      access to treatment. In this article, we review the relevant case law for the
      jurisdiction of the Ninth Circuit and place the medical-legal debate regarding
      these procedures in the context of recent cases. To address the medical-legal
      disjunction, we propose and discuss a model for managing treatment refusal in
      pretrial detainees found IST.

PMID- 22960927
TI  - PAS.

PMID- 22960928
TI  - Parental alienation (PA).

PMID- 22960929
TI  - Parental alienation syndrome (PAS).

PMID- 22960930
TI  - Extensive cross-talk and global regulators identified from an analysis of the
      integrated transcriptional and signaling network in Escherichia coli.
AB  - To understand the regulatory dynamics of transcription factors (TFs) and their
      interplay with other cellular components we have integrated transcriptional,
      protein-protein and the allosteric or equivalent interactions which mediate the
      physiological activity of TFs in Escherichia coli. To study this integrated
      network we computed a set of network measurements followed by principal component
      analysis (PCA), investigated the correlations between network structure and
      dynamics, and carried out a procedure for motif detection. In particular, we show
      that outliers identified in the integrated network based on their network
      properties correspond to previously characterized global transcriptional
      regulators. Furthermore, outliers are highly and widely expressed across
      conditions, thus supporting their global nature in controlling many genes in the
      cell. Motifs revealed that TFs not only interact physically with each other but
      also obtain feedback from signals delivered by signaling proteins supporting the
      extensive cross-talk between different types of networks. Our analysis can lead
      to the development of a general framework for detecting and understanding global
      regulatory factors in regulatory networks and reinforces the importance of
      integrating multiple types of interactions in underpinning the interrelationships
      between them.

PMID- 22960931
TI  - Diminished temporal coding with sensorineural hearing loss emerges in background
      noise.
AB  - Behavioral studies in humans suggest that sensorineural hearing loss (SNHL)
      decreases sensitivity to the temporal structure of sound, but neurophysiological
      studies in mammals provide little evidence for diminished temporal coding. We
      found that SNHL in chinchillas degraded peripheral temporal coding in background
      noise substantially more than in quiet. These results resolve discrepancies
      between previous studies and help to explain why perceptual difficulties in
      hearing-impaired listeners often emerge in noisy situations.

PMID- 22960933
TI  - Spaces within spaces: rat parietal cortex neurons register position across three
      reference frames.
AB  - We recorded parietal cortex neurons as rats traversed squared spiral tracks.
      Spatial firing patterns distinguished the behaviorally identical track segments
      composing loops, yet recurred with increasing or decreasing amplitude across the
      five loops composing the full track. These results indicate that parietal cortex
      neurons simultaneously respond to spatial relationships in multiple external
      reference frames, a phenomenon that may reflect a neural mechanism for relating
      parts to a whole.

PMID- 22960932
TI  - REST-dependent epigenetic remodeling promotes the developmental switch in
      synaptic NMDA receptors.
AB  - NMDA receptors (NMDARs) are critical to synaptogenesis, neural circuitry and
      higher cognitive functions. A hallmark feature of NMDARs is an early postnatal
      developmental switch from those containing primarily GluN2B to primarily GluN2A
      subunits. Although the switch in phenotype has been an area of intense interest
      for two decades, the mechanisms that trigger it and the link between experience
      and the switch are unclear. Here we show a new role for the transcriptional
      repressor REST in the developmental switch of synaptic NMDARs. REST is activated
      at a critical window of time and acts via epigenetic remodeling to repress Grin2b
      expression and alter NMDAR properties at rat hippocampal synapses. Knockdown of
      REST in vivo prevented the decline in GluN2B and developmental switch in NMDARs.
      Maternal deprivation impaired REST activation and acquisition of the mature NMDAR
      phenotype. Thus, REST is essential for experience-dependent fine-tuning of genes
      involved in synaptic plasticity.

PMID- 22960935
TI  - Ring opening polymerization of rac-lactide by group 4 tetracarbamato complexes:
      activation, propagation and role of the metal.
AB  - A series of group 4 metal tetracarbamates M(O(2)CNR(2))(4) (M = Ti, R = Et, 1a; M
      = Zr, R = Et, 1b; (i)Pr, 1c; M = Hf, R = Et, 1d; R = (i)Pr, 1e) were studied as
      catalytic precursors in the solution polymerization of rac-lactide. The titanium
      complex but not the zirconium and hafnium ones increase the activity by addition
      of (i)PrOH. The structure of the carbamato ligand markedly influences the molar
      mass of polymer; the complexes with isopropyl carbamato ligands produced PLA with
      molar masses up to 94,000 g mol(-1). The main mechanistic aspects of the initial
      stages of the polymerization reactions were outlined by spectroscopic and
      computational analyses. In the case of zirconium and hafnium complexes, an
      interaction between a carbamato ligand and the CH unit of one lactide molecule is
      established at room temperature. This interaction is followed by the high
      temperature proton transfer from the lactide to the carbamato O-atom, affording a
      catalytic active alkoxy complex with release of CO(2) and NHR(2). The
      polymerization mediated by Ti(O(2)CNEt(2))(4) involves the release of a radical
      fragment [O(2)CNEt(2)], with consequent generation of a Ti(III) center. The
      propagating chain is an alcoholate ligand coordinated to a Ti(IV) centre and
      containing a radical mainly localized at the tail of the chain (DFT, EPR).

PMID- 22960934
TI  - Mnemonic representations of transient stimuli and temporal sequences in the
      rodent hippocampus in vitro.
AB  - A primary function of the brain is the storage and retrieval of information.
      Except for working memory, where extracellular recordings have shown persistent
      discharges during delay-response tasks, it has been difficult to link memories
      with changes in individual neurons or specific synaptic connections. We found
      that transient stimuli are reliably encoded in the ongoing activity of brain
      tissue in vitro. Patterns of synaptic input onto dentate hilar neurons predicted
      which of four pathways were stimulated with an accuracy of 76% and performed
      significantly better than chance for >15 s. Dentate gyrus neurons were also able
      to accurately encode temporal sequences using population representations that
      were robust to variation in sequence interval. These results demonstrate direct
      neural encoding of temporal sequences in the spontaneous activity of brain tissue
      and suggest a local circuit mechanism that may contribute to diverse forms of
      short-term memory.

PMID- 22960936
TI  - Analysis of reserve capacity and subsequent stenting in a case of subacute
      occlusion of the internal carotid artery.

PMID- 22960937
TI  - A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in
      malignant pleural mesothelioma.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment
      results may be improved by biomarker-directed therapy. We investigated the
      baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1,
      and class III beta-tubulin in a cohort of MPM patients treated with cisplatin
      vinorelbine. We further explored the possibility of combining markers into a
      treatment-response profile to increase the predictive power. METHODS: Formalin
      fixed paraffin-embedded tumor specimens from 54 MPM patients included in a phase
      II trial were evaluated for ERCC1, BRCA1, and class III beta-tubulin by
      immunohistochemistry (IHC). Immunostaining was quantified by an H-score and
      dichotomized according to upper quartile values. The ERCC1- and class III beta
      tubulin-status classified patients as treatment resistant (ERCC1 positive + class
      III beta-tubulin positive) or treatment responsive (ERCC1 negative + class III
      beta-tubulin negative). The remaining marker combinations were considered
      inconclusive. RESULTS: Fifty patients had tumor tissue available for IHC. Eleven
      had a responsive profile, and nine had a resistant profile. Thirty patients had
      an inconclusive profile. Median progression-free survival (PFS) was 6.7 months in
      the treatment-resistant group, 15.3 months in the treatment-responsive group, and
      8.1 months in the inconclusive group (log-rank p = 0.03). Multivariate analysis
      revealed that treatment-resistant patients had a decreased PFS and overall
      survival (OS) compared with the treatment-responsive patients (HR 6.45, CI 95 %
      [2.02-20.64] p = 0.002 and HR 4.64, CI 95 % [1.56-13.79], p = 0.006,
      respectively). BRCA1 status was associated with neither PFS nor OS. CONCLUSION:
      Combined negative ERCC1 and class III beta-tubulin immunostaining is associated
      with significantly prolonged PFS and OS in MPM patients receiving cisplatin
      vinorelbine therapy.

PMID- 22960938
TI  - The pterocarpanquinone LQB 118 induces apoptosis in tumor cells through the
      intrinsic pathway and the endoplasmic reticulum stress pathway.
AB  - LQB 118 is a pterocarpanquinone compound synthesized by our group. It has already
      been shown that it acts against different leukemia cell lines. However, little is
      known about the pathway through which this compound induces the death of these
      cells. In this work, we analyzed the cell death process induced by LQB 118 in
      K562, a chronic myeloid leukemia cell line, and in Jurkat, a lymphoblastic acute
      leukemia cell line. For this, we carried out a cell viability assay by MTT, an
      apoptosis/necrosis assay through the annexin/propidium iodide label, cell cycle
      by flow cytometry, assessed changes in the mitochondrial membrane potential using
      DiOC6(3), cytoplasmic calcium analysis by Fluo-3-AM, and a caspase-9 and caspase
      12 activity assay. We found that LQB 118 induced apoptosis in both cell lines,
      measuring caspase-12 and caspase-9 activation, phosphatidylserine
      externalization, and DNA fragmentation. The compound induced an increase in
      cytoplasmic calcium on both cell lines. However, the compound could only induce
      mitochondrial membrane depolarization on K562 cells. Our data show that LQB 118
      may have potential therapeutic value for leukemia, being able to overcome
      multiple resistance mechanisms.

PMID- 22960939
TI  - Parenting practices and adolescent risk behavior: rules on smoking and drinking
      also predict cannabis use and early sexual debut.
AB  - Previous research has provided considerable support for idea that increased
      parental support and control are strong determinants of lower prevalence levels
      of adolescent risk behavior. Much less is known on the association between
      specific parenting practices, such as concrete rules with respect to smoking and
      drinking and adolescent risk behavior. The present paper examined whether such
      concrete parental rules (1) have an effect on the targeted behaviors and (2)
      predict other, frequently co-occurring, risk behaviors (i.e., cannabis use and
      early sexual intercourse). These hypotheses were tested in a nationally
      representative sample of 12- to 16-year-old adolescents in the Netherlands. We
      found that both types of rules were associated with a lower prevalence of the
      targeted behaviors (i.e., smoking and drinking). In addition, independent of
      adolescent smoking and drinking behaviors, parental rules on smoking predicted a
      lower prevalence of cannabis use and early sexual intercourse, and parental rules
      on alcohol use also predicted a lower prevalence of early sexual intercourse.
      This study showed that concrete parental rule setting is more strongly related to
      lower levels of risk behaviors in adolescents compared to the more general
      parenting practices (i.e., support and control). Additionally, the effects of
      such rules do not only apply to the targeted behavior but extend to related
      behaviors as well. These findings are relevant to the public health domain and
      suggest that a single intervention program that addresses a limited number of
      concrete parenting practices, in combination with traditional support and control
      practices, may be effective in reducing risk behaviors in adolescence.

PMID- 22960940
TI  - Predicting risk-taking with and without substance use: the effects of parental
      monitoring, school bonding, and sports participation.
AB  - Risk-taking is statistically normative during adolescence, yet is associated with
      adverse outcomes including substance use. The present study draws the distinction
      between protective factors (effective for those identified as high risk takers)
      and promotive factors (effective for all) against substance use, focusing on
      parental monitoring, school bonding, and sports participation. A total of 36,514
      8th and 10th grade participants in the national Monitoring the Future study were
      included. Although parental monitoring was associated with lower alcohol and
      marijuana use among all adolescents (i.e., promotive effect), these effects were
      strongest among the highest risk takers (i.e., protective effect) and females.
      School bonding was associated with lower levels of both alcohol and marijuana use
      among all groups of adolescents, but these promotive effects were weak. Sports
      participation was associated with higher levels of alcohol use among all males
      and among 8th grade females who did not identify as high risk takers. Despite
      being a risk factor for alcohol use, sports participation did demonstrate a
      promotive effect against marijuana use among 10th grade females only, and
      especially so for high risk-taking females (i.e., protective effect). Overall,
      these findings suggest that of the three mechanisms studied, parental monitoring
      emerged as the most promising entry point for substance use prevention and
      intervention across groups, particularly for females and high risk-taking
      adolescents.

PMID- 22960941
TI  - Thrombosis, cancer and renal insufficiency: low molecular weight heparin at the
      crossroads.
AB  - BACKGROUND: Venous thromboembolism (VTE) and renal insufficiency are common in
      cancer patients. Prompt treatment is necessary to reduce the high rates of VTE
      related mortality and morbidity. VTE prophylaxis is underused in cancer patients.
      We review current recommendations for the treatment and prevention of VTE in
      cancer patients and discuss low molecular weight heparin (LMWH) use in cases of
      renal failure. DESIGN: This study is a retrospective literature review. RESULTS:
      There are few published recommendations for LMWH use in cancer patients with
      renal insufficiency. Treatment guidelines largely follow recommendations for
      other patients with renal failure. Enoxaparin therapy is complicated by the need
      for regular monitoring of renal function and anti-Xa levels and for dosage
      adjustment to prevent bleeding. Few data are available to support the systematic
      use of dalteparin. Tinzaparin is least likely to bioaccumulate in patients with
      renal failure. CONCLUSION: VTE is the second most common cause of death in cancer
      patients. Renal insufficiency is present in 50-60 % of cancer patients. Data from
      renal patients suggest that tinzaparin may be safe and effective for VTE
      treatment and prevention in cancer patients with renal failure.

PMID- 22960942
TI  - Methodology for the MASCC/ISOO Mucositis Clinical Practice Guidelines Update.
AB  - Members of the Mucositis Study Group of the Multinational Association of
      Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)
      recently completed the process of updating the MASCC/ISOO Clinical Practice
      Guidelines for the prevention and treatment of mucositis. These guidelines,
      originally published in 2004, and last updated in 2007, provide clinicians with
      objective, evidence-based recommendations for the management of mucositis
      secondary to cancer therapy. This brief paper describes the methodology used to
      conduct the most recent systematic review in 2011, and develop new guidelines,
      providing the basis for the update. The overriding aims of the process were to
      assess evidence of effectiveness of interventions for the prevention and
      treatment of mucositis and to produce clinical practice guidelines for the
      management of mucositis using best available evidence.

PMID- 22960943
TI  - Influence of polymorphisms and TNF and IL1beta serum concentration on the
      infliximab response in Crohn's disease and ulcerative colitis.
AB  - AIM: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and
      ulcerative colitis (UC), are partially attributable to an increased secretion of
      proinflamatory cytokines, such as tumour necrosis factor (TNF) and interleukin
      1beta (IL1beta), which play essential roles in the disease pathogenesis and are
      target molecules for specific therapy. Given the inter-individual variability in
      the response to the anti-TNF monoclonal antibody infliximab, the aim of our study
      was to explore the predictive value of TNF and/or IL1beta as surrogate markers of
      infliximab response. METHODS: Serial serum concentrations of TNF and IL1beta and
      TNF promoter region and IL1B polymorphisms were determined in 47 patients (29 CD
      and 18 UC) receiving infliximab and correlated with treatment response. RESULTS:
      Baseline serum concentrations of TNF and IL1beta were higher in UC patients than
      in CD patients (p = 0.0097 and 0.0024, respectively). CD patients showing <0.64
      pg/ml IL1beta at baseline were more frequently responders than non-responders (p
      = 0.036), and the C allele of the IL1B polymorphism was associated with higher
      IL1beta serum concentrations (p = 0.026) and with poorer clinical remission after
      14 weeks of infliximab treatment. No significant association was found between
      serum TNF concentration or TNF polymorphism and patient response to infliximab.
      CONCLUSION: This is the first study evaluating the pharmacogenetic role of the
      rs1143634 polymorphism of IL1B and TNF polymorphisms in infliximab-treated IBD
      patients. We found an association between the rs1143634 C allele and higher serum
      IL1beta concentrations and a lower response to infliximab treatment in CD
      patients that warrants the interest of future studies in larger and independent
      series.

PMID- 22960944
TI  - Social distance and immediate informal responses to violent victimization.
AB  - There are a number of ways that victims of violence informally handle attacks as
      they unfold. Their responses range in severity from physical resistance, to
      talking it out with the offender, to running away, to cooperating. Why do victims
      respond in a more or less severe manner? Cooney (2009) suggests that social
      distance is part of the answer: the further the relational or cultural distance
      between offender and victim, the more severe the latter's response. Using
      National Crime Victimization Survey data, we test hypotheses derived from this
      theory and find oppositional findings. Specifically, results indicate that closer
      social distance predicts more severe responses. We conclude by discussing the
      implications of this finding for future work, especially as relates to the study
      of self-protective behavior.

PMID- 22960945
TI  - A longitudinal examination of offending and specialization among a sample of
      Massachusetts domestic violence offenders.
AB  - A paucity of existing research focuses on longitudinal examinations of criminal
      trajectories among reoffenses committed by domestic violence offenders.
      Specifically, few studies have longitudinally assessed whether domestic violence
      offenders specialize, recidivating in domestic violence assault, or generalize,
      committing a range of personal and property crimes. Acknowledging these research
      deficiencies, the current study uses longitudinal data from a cohort of 317
      batterers who were processed in a domestic violence court to investigate the
      trajectories of domestic violence arrests and nondomestic violence arrests over a
      10-year period. The degree of overlap between domestic and nondomestic violence
      arrest trajectory groups is examined through a cross-tabulation and chi-square
      analysis. Logistic and multinomial regression models are applied to identify risk
      factors that distinguish trajectory groups. A PROC TRAJ procedure identifies two
      trajectory groups for domestic violence arrests (low and high rate) and three
      trajectory groups for nondomestic violence arrests (very low, low, and high
      rate). Results indicate that specialization among domestic violence offenders is
      rare-prior alcohol and drug crimes predict membership in the high-rate domestic
      violence arrest trajectory group and prior domestic violence arrests predict
      membership in both the low-rate and high-rate nondomestic violence arrest
      trajectories. Implications for future research and policy are discussed in this
      article.

PMID- 22960946
TI  - Predictors of relationship adjustment in female survivors of childhood sexual
      abuse.
AB  - The current study investigated: (1) the relationship between childhood sexual
      abuse (CSA) and four relationship adjustment variables (consensus, cohesion,
      affection, and satisfaction); (2) whether finding meaning in CSA and using mature
      defenses would predict relationship adjustment; and (3) whether meaning and
      mature defenses would moderate the association between CSA severity and
      relationship adjustment. The sample consisted of 287 undergraduate women, 95 of
      whom reported a history of CSA. All participants were involved in a romantic
      relationship at the time of the study. Results indicated a significant
      relationship between CSA history and dyadic consensus, whereby abused women
      reported less agreement with their partners than nonabused women. In the abused
      sample, CSA severity significantly predicted affection and mature defenses
      significantly predicted both affection and consensus in relationships.
      Furthermore, mature defenses moderated the relationship between CSA severity and
      dyadic cohesion (i.e., joint activities with one's partner). Contrary to
      hypotheses, meaning was not related to relationship adjustment and did not
      moderate the association between CSA severity and relationship adjustment. These
      findings advance the CSA literature by elucidating factors that predict healthy
      adjustment to CSA.

PMID- 22960947
TI  - Implications of the prostate intervention versus observation trial (PIVOT).
AB  - PSA screening improves early detection of prostate cancer but can lead to
      overtreatment if all of these cancers are treated. The first randomized treatment
      study for men with PSA detected cancers has now been reported. The PIVOT
      (prostatectomy intervention versus observation trial) results are noteworthy.
      There were no overall or cancer-specific survival benefits from radical
      prostatectomy versus observation. This result was primarily driven by the largest
      subset, men with 'low risk' prostate cancer (organ-confined, Gleason 6, and PSA
      ,10 ng ml-1). Even though men enrolled in PIVOT were older and sicker as compared
      to most radical prostatectomy series, there was a strong tendency toward improved
      prostate cancer specific survival for participants with a PSA .10 ng ml-1 or
      Gleason scores of 7 or higher. This important study underscores the benefits of
      observation for those with 'low risk' prostate cancer and the potential benefits
      of surgery for those in higher risk categories.

PMID- 22960948
TI  - Molecular imaging of fibrin in a breast cancer xenograft mouse model.
AB  - RATIONALE AND OBJECTIVES: Fibrin deposition has been indicated within the stroma
      of a majority of solid tumors. Here we assess the feasibility of using the
      established fibrin-specific probe EP-2104R for noninvasive imaging of fibrin in
      the context of breast cancer. METHODS: EP-2104R, untargeted gadopentetate
      dimeglumine (Gd-DTPA), and a newly synthesized nonfibrin binding control linear
      peptide (CLP) were compared using steady-state and dynamic contrast-enhanced
      magnetic resonance imaging in a breast cancer xenograft mouse model at 9.4 T.
      RESULTS: EP-2104R transiently enhanced both tumor core and tumor periphery, but
      only the enhancement in the tumor periphery persisted even 90 minutes after EP
      2104R administration. However, untargeted Gd-DTPA and CLP are not retained in the
      tumor periphery. The half-life of EP-2104R in the tumor periphery (103 +/- 18
      minutes) is significantly longer (P < 0.05) than that of either Gd-DTPA (29.6 +/-
      2.4 minutes) or CLP (42.4 +/- 1.5 minutes), but the rate of clearance is similar
      for all the 3 probes from the tumor core. The presence of high concentrations of
      fibrin in the tumor periphery was corroborated using immunohistochemistry with a
      fibrin-specific antibody. CONCLUSIONS: The persistent enhancement observed in the
      tumor periphery with EP-2104R is likely a result of its fibrin-specific binding
      rather than its size and demonstrates the feasibility of EP-2104R for molecular
      imaging of fibrin in tumor stroma.

PMID- 22960949
TI  - A prospective, randomised, multicenter trial for surgical treatment of central
      retinal vein occlusion: results of the Radial Optic Neurotomy for Central Vein
      Occlusion (ROVO) study group.
AB  - BACKGROUND: To compare the surgical outcomes and evaluate the effectiveness of
      two treatments for central retinal vein occlusion (CRVO), radial optic neurotomy
      (RON) and intravitreal triamcinolone (IVT), in comparison to natural history.
      METHODS: A prospective, placebo-controlled, randomised and multi-center study.
      Patients with CRVO were treated in three groups - with either RON, a single
      intravitreal injection of 4 mg triamcinolone acetonide, or a placebo treatment.
      The main outcome measures were change of VA (visual acuity) and proportion of
      eyes with a significant improvement (defined as > 3 lines logMAR scale) of VA
      from baseline to month 12. RESULTS: Ninety patients were included. Due to
      insufficient data, seven were excluded. Forty-seven percent (n = 18) of patients
      treated with RON showed an increase in VA, in comparison to 10 % (n = 2) of
      placebo-treated patients, and 20 % (n = 5) of patients treated with IVT.
      Significantly more patients showed an improvement in VA following RON than in the
      placebo group (p = 0.009). Significantly more patients showed an improvement in
      VA following RON than in the IVT group (p = 0.034). No significant difference was
      found when directly comparing improvement in VA following IVT and placebo (p =
      0.667) treatment.Significantly (p = 0.007) more patients in the placebo group (35
      %, n = 7) showed a deterioration (defined as > 3 lines LogMAR scale) in VA than
      patients in the RON group (8 %, n = 3). CONCLUSION: Our study showed that
      following treatment with RON, patients with CRVO display a significantly better
      long-term VA than untreated patients and patients treated with a single dose of
      IVT.

PMID- 22960950
TI  - Clinical efficacy of laparoscopic sleeve gastrectomy vs laparoscopic gastric
      bypass in obese type 2 diabetic patients: a retrospective comparison.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are
      performed in patients with obesity and type 2 diabetes mellitus (T2DM). The aim
      of this study is to evaluate retrospectively the clinical efficacy of RYGB and SG
      in two groups of obese T2DM patients. METHODS: From the hospital database, we
      extracted the clinical records of 31 obese T2DM patients, of whom 15 (7 F/8 M)
      had undergone laparoscopic SG (LSG) and 16 (7 F/9 M) laparoscopic RYGB (LRYGB) in
      the period 2005-2008. The groups were comparable for age (range 33-59 years) and
      BMI (range 38-57 kg/m(2)). LRYGB alimentary limb was 150 cm, and biliopancreatic
      limb was 150 cm from the Treitz ligament. LSG vertical transection was calibrated
      on a 40-Fr orogastric bougie. Data were analysed at 6, 12 and 18-24 months with
      reference to weight loss and remission of comorbidities. RESULTS: The reduction
      in body weight was comparable in the two groups. At 18-24 months the percent BMI
      reduction was 29 +/- 8 and 33 +/- 11 % in LSG and LRYGB, respectively. Percent
      excess weight loss was 53 +/- 16 and 52 +/- 19 % in LSG and LRYGB, respectively.
      Thirteen patients in LSG and 14 patients in LRYGB discontinued their
      hypoglycaemic medications. Five (55 %) patients in LSG and eight (89 %) in LRYGB
      discontinued antihypertensive drugs. Three out of five patients in LSG and one
      out of two patients in LRYGB withdrew lipid-lowering agents. CONCLUSIONS: LSG and
      LRYGB are equally effective in terms of weight loss and remission of obesity
      related comorbidities. Controlled long-term comparisons are needed to establish
      the optimal procedure in relation to patients' characteristics.

PMID- 22960951
TI  - Gastric plication for morbid obesity: a systematic review.
AB  - BACKGROUND: Gastric plication is a new bariatric procedure. Controversies exist
      regarding this emerging surgery. We herein present a comprehensive review of the
      literature regarding gastric plication approach. METHODS: Advanced Pub Med search
      combining the MeSH terms "Gastric plication", OR "Gastric greater curvature
      plication" yielded 213 abstracts. Abstracts were screened for articles in English
      and articles on human subjects yielding 130. Further searches revealed 121 titles
      to be unrelated to gastric plication. The remaining nine abstracts were analyzed
      for their full texts. Two articles were excluded because, one was a commentary on
      another article, and the other was a released ASMBS policy on gastric plication.
      In the end, there were seven articles published on gastric plication. RESULTS: A
      total of 307 patients had undergone gastric plication. The mean operative time
      range was 40 to 150 min. The median length of hospital stay ranged between 1.3
      and 1.9 days. In respect to excess weight loss (EWL), at 6 months, it ranged from
      54 to 51 %, while at 12 months 67-53.4 %. The longest follow-up was 3 years with
      a mean of 57 % EWL. CONCLUSION: Laparoscopic gastric plication is still in its
      infancy. Prospective randomized studies comparing gastric plication to other well
      established bariatric procedures are needed to prove the reliability and
      metabolic effectiveness of such new procedure.

PMID- 22960952
TI  - Bacterial microsystems and microrobots.
AB  - Microorganisms and specifically motile bacteria have been recently added to the
      list of micro-actuators typically considered for the implementation of
      microsystems and microrobots. Such trend has been motivated by the fact these
      microorganisms are self-powered actuators with overall sizes at the lower end of
      the micrometer range and which have proven to be extremely effective in low
      Reynolds number hydrodynamic regime of usually less than 10(-2). Furthermore, the
      various sensors or taxes in bacteria influencing their movements can also be
      exploited to perform tasks that were previously considered only for futuristic
      artificial microrobots. Bacterial implementations and related issues are not only
      reviewed, but this paper also proposes many techniques and approaches that can be
      considered as building blocks for the implementations of more sophisticated
      microsystems and microrobots.

PMID- 22960953
TI  - Chemotactic steering of bacteria propelled microbeads.
AB  - Flagellated bacteria have been embraced by the micro-robotics community as a
      highly efficient microscale actuation method, capable of converting chemical
      energy into mechanical actuation for microsystems that require a small payload
      and high rate of actuation. Along with being highly motile, Serratia marcescens
      (S. marcescens), our bacterium species of interest, is a highly agile biomotor
      capable of being steered via chemotaxis. In this paper, we attached S. marcescens
      bacteria to polystyrene microbeads towards creating biohybrid that can propel
      themselves towards an attractive chemical source. Using a three-channel
      microfluidic device, linear chemical gradients are generated to compare the
      behavior of bacteria-propelled beads in the presence and absence of a
      chemoattractant, L-aspartate. We tested and compared the behavior of three
      different bacteria-attached bead sizes (5, 10 and 20 MUm diameter) using a visual
      particle-tracking algorithm, and noted their behavioral differences. The results
      indicate that in the presence of a chemoattractant, the S. marcescens-attached
      polystyrene beads exhibit a clear indication of directionality and steering
      control through the coordination of the bacteria present on each bead. This
      directionality is observed in all bead size cases, suggesting potential for
      targeted payload delivery using such a biohybrid micro-robotic approach.

PMID- 22960955
TI  - Towards improving cervical cancer screening in Nigeria: a review of the basics of
      cervical neoplasm and cytology.
AB  - Cervical cancer screening is the key to reducing the incidence and mortality of
      cervical cancer in developing countries. In the absence of a national screening
      program, healthcare givers in Nigeria are encouraged to routinely inform and
      screen eligible women. This review aims at equipping health workers for this task
      by re-educating them on the basics of the disease and its screening by cytology.
      Relevant texts and online databases including Pubmed, African Journal Online, and
      Google Scholar, were searched for relevant literature on the subject area.
      Persistent infection by a high-risk human papilloma virus, especially types 16
      and 18, is necessary for the development of cervical cancer. The exfoliation of
      cells from the metaplastic squamous cells of transformation zone of the cervix is
      the basis of cervical cytology. Organized Pap screening reduces the incidence and
      mortality of cervical cancer, but screening protocols vary. Nevertheless, annual
      screening is not recommended except for high-risk women such as HIV-positive
      women. Abnormal Pap smear results are currently reported using either the
      Bethesda System or the British Society for Clinical Cytology classification, and
      colposcopy with or without biopsy are necessary when indicated. In conclusion,
      the use of cervical cytology to detect pre-cancerous lesions followed by an
      appropriate treatment when necessary is the key to reducing invasive cervical
      cancer. The task of provider-initiated counseling and testing for cervical cancer
      by health practitioners requires update on the current etio-pathology of cervical
      cancer, and its screening as reviewed.

PMID- 22960954
TI  - A novel double antibody sandwich-lateral flow immunoassay for the rapid and
      simple detection of hepatitis C virus.
AB  - The objective of this study was to screen for antigens of the hepatitis C virus
      (HCV) to establish a new double antibody sandwich-lateral flow immunoassay (DAS
      LFIA) method for testing the presence of anti-HCV antibodies in human serum or
      plasma. A series of different recombinant HCV proteins in Escherichia coli cells
      were constructed, expressed, purified and the new DAS-LFIA strip was developed.
      The sensitivity and specificity of new the DAS-LFIA strip were evaluated by
      detecting 23 HCV-positive sera, a set of quality control references for anti-HCV
      detection that contain known amounts of anti-HCV antibodies, and 8 HCV-negative
      sera. A total of 300 clinical serum samples was examined by both the new DAS-LFIA
      strip and enzyme-linked immunosorbent assay (ELISA). Data were analyzed using
      SPSS 11.5 software. The sensitivity and specificity of the new DAS-LFIA strip
      were 100%. The lowest test line of the HCV DAS-LFIA strips was 2 NCU/ml.
      Additionally, the concordance between the new DAS-LFIA strip and ELISA methods
      was 94.33%. In conclusion, our new testing method is rapid, simple, sensitive and
      specifically detects the presence of anti-HCV antibodies in human serum or
      plasma. Therefore, it may be used for monitoring HCV.

PMID- 22960956
TI  - Management of pheochromocytoma: old ideas and new drugs.
AB  - Pheochromocytoma presents a challenge to the surgery team because of its clinical
      features and implications. The patient must be treated before the surgery until a
      stable hemodynamically state is achieved. The preoperative treatment includes
      alpha2-short acting adrenergic blocking and beta-blocker agents. The most crucial
      intraoperative moments are induction of anesthesia and hemodynamic oscillations.
      An adequate preoperative preparation, modern anesthetic drugs, good collaboration
      between the surgeons and the anesthesiologists, and postoperative care decrease
      the rate of complications and improve the outcome. This review aims to discuss
      all the possible pharmacological strategies of perioperative management of
      phoechromocytoma, focusing on new drugs and treatments.

PMID- 22960957
TI  - Association between blood pressure and urinary electrolytes in a population of
      nonurban-dwelling Nigerians.
AB  - BACKGROUND: Little is known about the association between blood pressure and
      urinary electrolytes in young adult, nonurban-dwelling, sub-Saharan Africans.
      This study attempts to provide such data in a Nigerian population. PATIENTS AND
      METHODS: Four hundred Nigerians (50% female) aged 19-40 years were studied. Their
      blood pressures (BPs), anthropometric variables, and overnight urinary sodium,
      and potassium concentrations (UNaC and UKC respectively) were measured using
      standard procedures. Associations between measures of BP and the other parameters
      were examined using appropriate statistical tools. RESULTS: UNaC was correlated
      significantly with only diastolic BP (DBP) (r = +0.105, P = 0.037). Similarly,
      UNaC was significantly associated with DBP and mean BP (MBP) (beta = +0.158, P =
      0.018 and beta = +0.155, P = 0.020, respectively). UKC was not associated with,
      nor correlated with, any measure of BP. There was no significant mean difference
      (P > 0.05) between the sexes for measures of BP and urinary electrolytes.
      CONCLUSION: Urinary sodium (but not potassium) concentration was weakly
      correlated with only DBP, and weakly associated with only DBP and MBP in the
      studied population. The results support (modestly) the hypothesis that dietary
      sodium intake may be related to elevated blood pressure.

PMID- 22960958
TI  - Default from neoadjuvant chemotherapy in premenopausal female breast cancer
      patients: what is to blame?
AB  - BACKGROUND: Breast cancer is the most frequent cancer among women in most parts
      of the world including Nigeria. Neoadjuvant chemotherapy has been demonstrated to
      be a helpful strategy in the context of locally advanced breast cancer. AIMS: The
      purpose of this study was to investigate some factors that may contribute to low
      rate of acceptance and adherence to neoadjuvant chemotherapy. MATERIALS AND
      METHODS: A 1-year prospective study of premenopausal women with locally advanced
      breast cancer recommended for neoadjuvant chemotherapy from June 2009 to May
      2010. RESULTS: Forty-four patients gave consent to be part of the study. The ages
      ranged from 26 to 51 years with a mean age of 42.1 years +/- 7.7 years. Only 31
      patients completed the four courses of NAC. Seventeen (38.6%) patients dropped
      out of treatment, before, during or after completing NAC. Ten of these defaulted
      due to inadequate funds to procure chemotherapy, three patients because they
      insisted on immediate mastectomy, and four of these patients refused surgery when
      they achieved complete clinical response, probably due to fear of mastectomy
      which is common among women in our environment. Twenty patients had dose
      deferment. CONCLUSION: Lack of funds to procure chemotherapy and refusal of
      additional modality of treatment are the two major factors responsible for
      default of NAC and its goal in patients with LABC.

PMID- 22960959
TI  - Prevalence of tobacco use among dental patients and their knowledge of its health
      effects.
AB  - OBJECTIVES: The objective of this study was to determine the prevalence of
      tobacco use in dental patients, to compare the knowledge of the effects of
      tobacco in tobacco users and nonuser, to determine their source of information,
      and to obtain their opinion on strategies that may be used to reduce or stop
      tobacco consumption. MATERIALS AND METHODS: A descriptive cross-sectional survey
      of 400 patients attending the University of Benin Teaching Hospital dental clinic
      for treatment was carried out using a self-administered questionnaire. RESULTS:
      The result revealed that the prevalence of tobacco use is 4.25% and that tobacco
      was consumed in the form of cigarette in 94% of cases. Only a small percentage of
      the respondents (0.3%) had a poor knowledge of both the tobacco effect on general
      and oral health. Although 26.5% claimed to have multiple source of information on
      the effect of tobacco on health but the media was the highest single source
      (23.5%). Banning of sales of tobacco products was suggested by 30.5% of the
      respondents, 19.8% suggested that doctor should educate patients on the health
      effect of tobacco, and 17.8% feel that to discourage tobacco use, multiple
      strategies should be used. CONCLUSION: There is a need for health workers to lay
      more emphasis on the rare complications of tobacco use. The use of multiple
      regulatory strategies should be employed to reduce the overall adverse health
      impact of tobacco and the media can play a great role.

PMID- 22960960
TI  - An assessment of psychiatric disturbances in Graves disease in a medical college
      in eastern India.
AB  - BACKGROUND: Graves' disease is a unique conglomeration of cardiovascular,
      neurological, ophthalmological, and other systemic manifestations. In this study
      we have tried to explore the psychiatric dimensions of this disease. AIMS: This
      study attempted to explore clinical features, types, and treatment outcome of
      psychiatric disturbances in Graves disease. STUDY DESIGN: This is a purposive
      study following the criteria of DSM IV. MATERIALS AND METHODS: A total of 36
      adult patients of newly diagnosed Graves disease and 30 age- and sex-matched
      controls were included. Data enumerated were age, sex, date of admission,
      analysis of psychiatric signs, and symptoms by one independent observer,
      diagnostic categorization, effect of treatment, and outcome. Follow-up evaluation
      was done after 1 year. Statistical Analysis : Statistical analysis was done by
      the standard error of difference, the chi-square test, and paired Student's T
      test. RESULTS: Among 36 patients 32 were female and 4 were male. Fifteen patients
      (41.67%) were diagnosed with generalized anxiety disorders (GAD), 6 (16.67%) with
      mood disorder, 6 (16.67%) with obsessive compulsive disorder (OCD), and 2 each
      with personality disorder and schizophreniform disorder. The common symptoms were
      insomnia, irritability, and anxiety. The frequency of GAD was statistically more
      significant in the Graves disease group in comparison to control. Fourteen
      patients agreed to take both antithyroid and antipsychotropic medications (group
      1). The rest were treated with only antithyroid drug (group 2). There was
      significant improvement in both groups and no difference between the groups.
      CONCLUSION: The prevalence of certain psychiatric manifestations in Graves'
      disease was significantly higher than in the control group. There was no
      significant difference between therapy with antithyroid drugs and combination of
      antithyroid with psychotropic medications.

PMID- 22960961
TI  - Outcome of surgery for toxic goitres in Maiduguri: a single teaching hospital's
      perspective.
AB  - BACKGROUND: Thyrotoxicosis a common endocrine disorder of the thyroid gland in
      Nigeria is commonly treated surgically. The outcome of thyroidectomy for toxic
      goiters in Maiduguri Nigeria is evaluated. MATERIALS AND METHODS: Over the last 5
      years (Jan 2005-July 2010) , in a prospective review, the demographic, and
      clinical data of patients operated for toxic goiters in our department was
      entered, into a predesigned proforma and analyzed. The objective of the study is
      to review our experience with subtotal and near-total thyroidectomy as treatment
      for benign toxic goiters. RESULTS: Seventy-eight patients, 11 males (14.1%) and
      67 females (85.9%), with male: female ratio of 1:6.1 and the mean age of 30 +/-
      10.9 (range, 17-65 years), underwent thyroidectomy for toxic goiters. The mean
      duration of symptoms was 41.9 (range 3-126 months). There were 53 patients with
      toxic diffuse goiters (Grave's disease) with their mean age of 27.6 +/- 6.93
      (range 17-38 years), 23 with toxic multinodular goiters, the mean age of 43.7 +/-
      15.68 (range 17-65 years) and two with toxic nodule. There was no case of
      permanent recurrent laryngeal nerve palsy or permanent hypocalcemia. Transient
      hypocalcemia occurred in 9 (11.5%) patients and hemorrhage with hematoma,
      requiring exploration in 4 (5.1%). There were two cases of wound infection and no
      postoperative mortality. The mean hospital stay was 7.6 +/- 2.34 (range 5-15
      days). There was no disease recurrence over a mean follow-up of 20.7 (range 2-48)
      months. CONCLUSION: Subtotal thyroidectomy is an effective procedure for the
      treatment of thyrotoxicosis with few postoperative complications and majority of
      patients being euthyroid after long follow-up.

PMID- 22960962
TI  - Comparative ultrasound measurement of normal thyroid gland dimensions in school
      aged children in our local environment.
AB  - OBJECTIVE: The objective of this study was to determine the measurement of normal
      range of ultrasound (US) thyroid gland dimensions in school-aged children (6-16
      years) in our environment and compared with what is obtained elsewhere. SETTING
      AND DESIGN: A prospective ultrasound measurement study done in University of
      Benin Teaching Hospital Benin, Nigeria. MATERIALS AND METHODS: A prospective
      ultrasound (US) study of thyroid dimensions of 500 school-aged children in our
      environment consisting of 227 boys and 273 girls was done from 1 December 2006 to
      July 2007. The subjects were examined by the authors and subjects with palpable
      abnormal thyroid gland were excluded from the study. The thyroid dimensions
      (length, height, and diameter) were taken for each lobe by means of ultrasound
      (US). In addition volume of each thyroid lobe was calculated and the summation of
      volume of the lobes was taken as thyroid gland volume of each subject. Also
      height and weight of patients were documented from which the subject's body
      surface was calculated. Incidental thyroid gland lesion in US was excluded from
      the study. Using the Statistical program of social science (SPSS) and INSTAT
      (Graph Pad Inc. USA) the data were analyzed. Informed consent was obtained from
      all the subjects and the study was done in line with the ethical guidelines of
      the centers. RESULTS: The US thyroid gland volume in school-aged children in
      Benin City from this study ranges between 1.17 cm 3 and 7.19 cm 3 , mean volume
      range of 1.76-4.95 cm 3 , median volume range of 1.73-4.73 cm 3 , and range of
      standard deviation from 0.39 cm 3 to 1.49 cm 3 . The average mean thyroid volume
      is 2.32 cm 3 with the following average dimensions; anteroposterior right lobe
      =1.06 cm, mediolateral right lobe = 1.01 cm and craniocaudal right lobe = 2.34
      cm, and anteroposterior left lobe = 1.01 cm, mediolateral left lobe = 1.04 cm and
      craniocaudal left lobe = 2.41 cm for both boys and girls respectively. These data
      are significantly lower than data obtained by European based World Health
      Organization/International Council for the Control of Iodine Deficiency Disorders
      (WHO/ICCIDD) 1997. However there is significant similarity with data obtained in
      similar environment. CONCLUSION: Ultrasound thyroid gland dimensions in school
      aged children in our environment are reproducible and the data obtained are
      comparable to those obtained in other environment. The values may be better used
      in our environment as reference data for screening purposes.

PMID- 22960963
TI  - Diagnostic value of lipids, total antioxidants, and trace metals in benign
      prostate hyperplasia and prostate cancer.
AB  - BACKGROUND: Considerable overlap exists in the value of total prostate specific
      antigen (tPSA) in both prostate cancer (Pca) and benign prostate hyperplasia
      (BPH). Developing an effective biochemical screening test that will complement
      PSA assay could reduce the associated cost of care and give timely attention to
      prostate cancer patients even when they are still asymptomatic is therefore
      desirable. This work was therefore an attempt to evaluate the possible roles of
      lipids, antioxidants, and trace metals in breaking the diagnostic tie between Pca
      and BPH. MATERIALS AND METHODS: Anthropometric characteristics, total prostate
      specific antigen (tPSA), serum lipids (total cholesterol, LDL cholesterol, HDL
      cholesterol, and triglycerides), Vit. E, total antioxidant status (TAS), and
      trace metals (Se, Cu, Fe, Zn, and Mn) were determined in 40 patients with
      histopathological diagnosis of BPH and Pca. Forty age matched control subjects
      were also recruited from the same community. Informed consent was obtained from
      all the participants in the study. A P-value < 0.05 was considered significant.
      RESULTS: There were significant variations in the weight, hip circumference, and
      body mass index (BMI) across the group but the post hoc test did not show any
      difference between patients with prostate cancer and BPH. Among the biochemical
      parameters studied, only the total cholesterol and triglyceride differed
      significantly between patients with BPH and prostate cancer patients. Cut-offs
      from ROC for BPH and prostate cancer at 88.9 sensitivity and 66.7% specificity
      (95% CI) were 88.5 mg and 161 mg/dl for triglycerides and cholesterol
      respectively. Furthermore there were no significant variations in the mean levels
      of copper and tPSA, Vit E, and LDL cholesterol among the study subjects and the
      controls. CONCLUSION: Prior to prostate biopsy, serum lipid (especially, fasting
      triglycerides, total cholesterol) could help in early discrimination of patients
      with BPH from prostate cancer in adjunct to total PSA and other management
      protocol for diagnosis of prostate cancer. The use of trace metal or antioxidants
      may have limited advantages. Further studies in this regard will be very
      desirable to see if this pattern of triglyceride and total cholesterol values in
      BPH and Pca are sustainable.

PMID- 22960964
TI  - Ocular changes in pregnant Nigerian women.
AB  - OBJECTIVE: Pregnancy results in a lot of hormonal changes in the body and the
      eyes are no exception. These ocular changes could be physiologic, pathologic or a
      modification of a pre-existing condition. The aim of this study was to determine
      physiologic ocular changes that are associated with pregnancy in healthy Nigerian
      women. MATERIALS AND METHODS: A total of 100 women were followed longitudinally
      through out the course of their pregnancy and 6 weeks postpartum. The women were
      recruited at 8 weeks of pregnancy at the anti-natal clinic in the Department of
      Obstetrics and Gynecology, University of Benin Teaching Hospital, Nigeria. The
      women were aged between 20 and 35 years. Tests carried out included visual
      acuity, ophthalmoscopy, retinoscopy, and tonometry. The tests were carried out in
      each of the three trimesters of pregnancy and 6 weeks postpartum. RESULTS: There
      was a fall in intraocular pressure across the trimesters and this was very
      significant (P<0.0001). Postpartum, the intraocular pressure began to rise. The
      difference between the third trimester and post-partum values was also
      statistically significant (P< 0.0001). The difference in visual acuity through
      out the pregnancy was not significant (P= 0.8477). Although, there was a fall in
      refractive error across the different trimesters, it was not statistically
      significant (P=0.3). There was also no difference in the third trimester and the
      6 weeks postpartum values of both visual acuity and refractive error. CONCLUSION:
      Ocular changes associated with pregnancy are transient and most tend to resolve
      postpartum, with values returning to near pre-pregnant state.

PMID- 22960965
TI  - Oral health practices among pregnant women in North Eastern Nigeria.
AB  - OBJECTIVE: The objective of this study was to document oral health practices of
      pregnant women in two tertiary institutions in North-eastern Nigeria. MATERIALS
      AND METHODS: This was a cross-sectional study of pregnant women seen at the
      antenatal clinics of the University of Maiduguri Teaching Hospital and Federal
      Medical Centre Yola from May 1, 2009 to July 1, 2009. RESULTS: A total of 294
      women were interviewed. They were aged 15-46 with a mean of 27.42 +/- 5.97 years.
      The parity ranged from 1 to 9 with a mean of 2.23 +/- 1.65. Twelve (4.1%) women
      gave a history of symptomatic oral lesion in index pregnancy. Forty-four (15%)
      had had previous encounter with a dentist, while the highest frequency of oral
      care was twice a day in 164 (55.8%) of respondents. The majority, 264 (89.9%),
      used toothbrush/toothpaste as a form of oral care while 2 (0.7%) used charcoal.
      Women of low parity tended to have better oral care than those of high parity (P
      = 0.002). Women who are employed had better oral care than housewives (x2 =
      27.749, P = 0.001). There was no significant relationship between oral complaints
      and trimester of pregnancy (x2 = 4.271, P = 0.118). CONCLUSION: Oral healthcare
      among the respondents was encouraging but involvement of the dental surgeon in
      preventive oral care in pregnancy is rather dismal.

PMID- 22960966
TI  - Prevalence of three-rooted mandibular permanent first molars among the Turkish
      population.
AB  - BACKGROUND: This retrospective study was undertaken to determine the prevalence
      of three-rooted permanent mandibular first molars in digital periapical
      radiographic images obtained from a Turkish patient. MATERIALS AND METHODS:
      Periapical radiographs of 640 subjects, which had been obtained in the Department
      of Oral Diagnosis Radiology, Kirikkale University Dental Faculty, Kirikkale,
      Turkey from June 2010 to March 2011, were screened and examined retrospectively.
      All radiographs were evaluated under optimal conditions using double magnifying
      glasses. Each radiograph was separately evaluated by two authors (H.C. and
      M.M.H.). Comparison of the incidence and the correlations between males and
      females and left- and right-side occurrences were analyzed by using the Pearson
      chi-square test with SPSS (15.0; SPSS Inc., Chicago, IL, USA). RESULTS: The
      periapical radiographs of 9 patients, 4 females and 5 males, had three-rooted
      mandibular first molars. Of these three-rooted mandibular first molars, 7 were
      found on the right side and 5 on the left side. The overall incidence of patients
      with three-rooted mandibular first molars was 1.41%. The incidence was 1.63% for
      men and 1.2% for women. CONCLUSION: The prevalence of three-rooted mandibular
      first molars from all teeth examined was 1% (12 of 1205), 1.17% (7 of 596) for
      the right side, and 0.82% (5 of 528) for the left side occurrences.

PMID- 22960967
TI  - Visual outcome following optic neuritis: a 5-year review.
AB  - BACKGROUND: Optic neuritis is a demyelinating inflammatory disease of the optic
      nerve that typically affects young adults especially females, and is usually
      associated with multiple sclerosis especially in Caucasians. The prognosis for
      visual recovery is usually good but with poor quality. OBJECTIVE: The objective
      was to determine the level of improvement of vision after an attack of optic
      neuritis in Port Harcourt, Nigeria. DESIGN: A retrospective hospital-based study
      was performed. SETTING: Eye Clinic, University of Port Harcourt Teaching Hospital
      (UPTH), Port Harcourt, Nigeria. DATA EXTRACTION: Medical records of all cases of
      optic neuritis seen at the Eye Clinic of UPTH over a 5-year period (January 2006
      December 2010) were retrieved and relevant data including age, sex, presenting
      symptom, and visual acuity (VA) were extracted. The VA at discharge 12 weeks
      later was noted. Our diagnosis of optic neuritis was based on the presence of low
      vision, dyschromatopsia, and peri-ocular pain. RESULTS: Over 24,000 patients were
      seen during this period, and 27 cases were optic neuritis (0.1%). Of the 27 cases
      of optic neuritis, 20 cases were retro-bulbar neuritis (74.1%), while seven
      (25.9%) were papillitis. There were 16 females and 11 males giving a female to
      male ratio of 3:2. Most cases (75%) at presentation had VAs<6/24. By the 12 th
      week, most visual acuities (77.1%) had improved to 6/12 or better. CONCLUSION:
      This study confirms widely documented evidence that there is improvement in
      visual acuity after an attack of optic neuritis. Even though the risk of
      developing multiple sclerosis following optic neuritis is said to be low in
      blacks, these patients should still be followed up for sometime especially as
      some may go on to develop other complications of demyelination.

PMID- 22960968
TI  - Is extended biopsy protocol justified in all patients with suspected prostate
      cancer?
AB  - OBJECTIVE: To determine the significance of an extended 10-core transrectal
      biopsy protocol in different categories of patients with suspected prostate
      cancer using digital guidance. MATERIALS AND METHODS: We studied 125 men who were
      being evaluated for prostate cancer. They all had an extended 10-core digitally
      guided transrectal prostatic biopsy done for either an elevated serum prostate
      specific antigen (PSA) or an abnormal digital rectal examination finding or both.
      Sextant biopsy samples were collected first, followed by additional four lateral
      biopsies in all patients. Both groups of specimens were analyzed separately. The
      cancer detection rates of both sextant and extended 10-core biopsy protocols at
      different PSA levels and digital rectal examination (DRE) findings were
      determined and compared. The level of significance of difference in cancer
      detection was determined using Pearson's Chi square test with level of
      significance set at <0.05. RESULTS: The overall cancer detection by the extended
      technique was 61 (48.8%) cases while the sextant protocol detected cancer in 52
      cases. The 10-core extended protocol yielded an increase in cancer detection rate
      of 14.8% but the improvement in detection rate was only statistically significant
      in the sub-set of patients with PSA between 4.1 and 10 ng/mL, with or without
      abnormality on DRE, with an overall increase detection rate of 33%.(P=0.04)
      CONCLUSION: Our study has shown that a 10-core prostate biopsy protocol
      significantly improves cancer detection in patients with suspected early cancer.
      It should therefore be the optimum biopsy protocol for patients with gray-zone
      PSA value, with or without abnormal DRE.

PMID- 22960969
TI  - A retrospective study of traumatic injuries to teeth at a Nigerian tertiary
      hospital.
AB  - BACKGROUND: Various aspects of dental trauma have been studied worldwide. Most of
      these were among children and adolescents. However, studies involving the adult
      population with traumatized anterior teeth are few. OBJECTIVES: The objectives of
      this study were to report the pattern of trauma to anterior and posterior teeth
      among the late adolescent and adult patients seen at the Dental Centre,
      University College Hospital, Ibadan, Nigeria, the time lapse between trauma and
      patient presentation, reasons for dental consultation, and the type of treatment
      received. MATERIALS AND METHODS: Data were extracted from the dental records of
      146 patients with dental trauma that presented between May 2001 and June 2006.
      RESULTS: One hundred and forty six patients were studied (87 males, 59 females)
      Males sustained injury more than females. The highest occurrence of trauma was in
      the age group of 25-34 years and least in the >65 years. Falls accounted for
      34.3% of causes followed by RTA (19.2%). Enamel-dentine fracture was the most
      common type of injury, seen in 73 (38.6%) of the traumatized teeth, 5 were
      avulsed and 20 posterior teeth had cuspal fracture. All the cases of avulsion and
      most (83.3%) of root fracture presented within 1 week of injury while teeth that
      presented late had pulpal necrosis. 22% of the patients presented within 1 week
      of injury while 13.7% came after 10 years. CONCLUSION: There was late patients'
      presentation with average duration of trauma before presentation being 4.6 years;
      however the more severe the outcome of trauma, the earlier the presentation. Poor
      esthetics followed by pain were the main complaints at presentation.

PMID- 22960970
TI  - The effect of health education on the knowledge, attitude, and uptake of free Pap
      smear among female teachers in Birnin-Kebbi, North-Western Nigeria.
AB  - INTRODUCTION: The Routine Pap smear test has successfully reduced the incidence
      of invasive cervical cancer in the presence of a proper structure for its
      implementation. This study was designed to assess the effect of health education
      on the knowledge, attitude, and uptake of Pap smear among female teachers.
      MATERIALS AND METHODS: It was a quasi-experimental, controlled study with a pre
      test, post-test design. A total of 100 respondents were recruited for each of the
      intervention and control groups, by the multistage sampling technique. RESULTS:
      The mean knowledge score of cervical cancer was low in both the interventions
      (25.5% +/- 10.5) and control groups (18.9% +/- 10.0) at baseline; a significant
      rise to 57.2% +/- 20.7 was recorded after the intervention in the Intervention
      group (P<0.0001). The baseline mean attitude score was also low in the
      intervention and control groups (17.1% +/- 6.3 and 14.1% +/- 6.4, respectively);
      post intervention there was a significant rise of up to 28.0% +/- 12.8 in the
      Intervention group (P<0.0001). The proportion of respondents with a reported
      practice of Pap smear was low and similar in both the groups at baseline (1.1 and
      4.9% in the intervention and control groups, respectively, P=0.16). Uptake of
      free Pap smear was poor at the post-intervention phase in both the groups
      (P=0.45). Reported reasons for poor uptake included the respondents' dislike for
      the test (38.4%) and the belief that the test was not necessary (24.4%). About
      20% of the respondents did not have any reason at all. CONCLUSION: Health
      education had no significant effect on the uptake of a free Pap smear among
      teachers. Despite the significant improvement in the attitude toward the test,
      many respondents did not like the test after than before the intervention.
      Sociocultural issues such as the gender of the sample collector, and system
      factors like few service delivery points, and the time required to access the
      service could have contributed to the poor uptake recorded in this study. A
      program designed to improve routine cervical cancer screening by Pap smear should
      therefore address not only the knowledge and cost, but also the sociocultural and
      systemic factors.

PMID- 22960971
TI  - Common geriatric emergencies in a rural hospital in South-Eastern Nigeria.
AB  - BACKGROUND: Geriatric population in rural Nigeria is often challenged by
      emergency health conditions that predispose them to higher risk of disability and
      mortality. OBJECTIVE: This study was aimed at describing the common geriatric
      emergencies in a rural hospital in South-Eastern Nigeria. MATERIALS AND METHODS:
      This was a descriptive hospital-based study of 216 geriatric patients who
      presented between June 2008 and June 2011 with emergency health conditions at St
      Vincent De Paul hospital, Amurie-Omanze, a rural Mission General Hospital in Imo
      state, South-Eastern Nigeria. The geriatric patients seen within the study period
      who met the selection criteria were studied. Data extracted for analysis included
      biodata and diagnosis made. RESULTS: A total of 216 geriatric emergencies were
      seen during the study period. The ages of the patients ranged from 65 years to 98
      years with mean age of 72 +/- 1.14 years. There were 94 males and 122 females
      with a male to female ratio of 1: 1.3. The three most common causes of geriatric
      emergencies were acute malaria (33.8%), hypertensive crises syndrome (19.0%), and
      acute hypertensive heart failure (18.1%). CONCLUSION: This study has shown that
      the three most common geriatric emergencies were medical emergencies (acute
      malaria, hypertensive crises syndrome, and acute hypertensive heart failure).
      Improving the quality of geriatric medical care will help in reduction of these
      emergency medical conditions. Similarly, health education of the geriatric
      population to embrace early health-seeking behavior, health maintenance, and
      promotional practices that are needed to promote longevity is invariably
      advocated.

PMID- 22960972
TI  - Predicting mode of delivery using mid-pregnancy ultrasonographic measurement of
      cervical length.
AB  - BACKGROUND: It has been recognized that preterm labor is related to short
      cervical length and that poor progress in labor is a major indication for
      cesarean section at term. We therefore hypothesize that long cervix is not
      associated with increased risk of cesarean delivery during labor at term.
      OBJECTIVES: The objective is to determine the relationship between cervical
      length at mid-pregnancy and mode of delivery and preterm delivery. MATERIALS AND
      METHODS: Trans-vaginal ultrasonographic scan measurement of cervical length was
      done for 281 pregnant women at a mean gestational age of 22 weeks. These women
      were followed up till delivery and the mode of delivery and the cervical length
      were analyzed for associations. RESULTS: Cesarean section due to poor progress in
      labor at term constituted 11.7%. The cesarean section for the highest quartile
      cervical length (40-67 mm) was 50% (P value 0.0018 for trend). Of the 33 women
      whose mode of delivery was cesarean section due to poor progress 18 (54.5%) had
      cervical length of more than 40 cm. The likelihood ratio of cesarean section due
      to poor progress of labor at term among women at the upper quartile cervical
      length is 10.28 (P value 0.0013) CONCLUSION: Long cervical length at mid
      pregnancy predicts the possibility of cesarean delivery early in pregnancy.
      Hence, cervical length in mid-pregnancy can be of value in predicting the mode of
      delivery in early pregnancy.

PMID- 22960973
TI  - Retrospective evaluation of necrotizing fasciitis in University College Hospital,
      Ibadan.
AB  - CONTEXT: Cervicofacial necrotizing fasciitis (CNF), although a potentially fatal
      fulminant infection has been largely under-reported in the dental literature.
      AIMS: To report our experience with cases seen and treated at the University
      College Hospital, Ibadan, Nigeria. SETTINGS AND DESIGN: A descriptive
      retrospective clinical study. MATERIALS AND METHODS: A retrospective survey of
      cases treated between January 2002 and January 2007 was done. Diagnosis of CNF
      was established by fascia necrosis found on surgical exploration. Patients' age,
      sex, medical status, etiology of infection, bacteriology, and treatment received
      and complications were reviewed. STATISTICAL ANALYSIS USED: SPSS version 15.
      RESULTS: Of the 48 cases of cervicofacial infection admitted during the study
      period, only 12 cases of CNF were found. Male:Female ratio was 4:8. The mean age
      of patients was 58.83 +/- 11.91 years while the age range was 42-83 years. Those
      that had immunocompromised medical conditions included three cases each of
      diabetes mellitus and chronic nutritional anaemia and one case of retroviral
      infection. Mixed bacterial isolates of anaerobes and enterobacteriaceae were
      found in 10 cases while beta hemolytic streptococci were the sole isolate in two
      cases. All patients had serial debridement combined with intravenous antibiotic
      medications. Complications included anterior chest wall infection in three
      patients and one case of pleural effusion. The only mortality occurred in the
      patient with retroviral infection. CONCLUSIONS: We advocate early recognition,
      surgical debridement and intensive medical care for treatment of CNF in order to
      reduce morbidity and mortality from this condition.

PMID- 22960974
TI  - Route of transmission might influence the clinical expression of periodontal
      lesions in "human immunodeficiency virus" positive patients.
AB  - BACKGROUND: Various routes have been reported with respect to the transmission of
      human immunodeficiency virus (HIV) from one individual to another. But it is not
      clear whether they alter the clinical expression of the disease. This study was
      conducted to know whether there exists any difference in the occurrence of
      periodontal lesions among untreated HIV subjects who acquired the disease either
      through intravenous drug abuse or sexual contact and to correlate those lesions
      with immune suppression as indicated by CD 4 T lymphocyte counts. MATERIALS AND
      METHODS: In this cross-sectional study 213 HIV-positive subjects who had not
      started on Highly Active Anti Retroviral Therapy (HAART) were selected and
      divided into two groups intravenous drug users (IVDU) and non-IVDU (NIVDU). CD 4
      T lymphocyte counts were evaluated and clinical examination was done to detect
      the presence of pathologic periodontal lesions. RESULTS: Mean probing depth (PD)
      and clinical attachment level (CAL) are significantly higher in drug users than
      nondrug users. When periodontal lesions are compared with CD 4 cell counts, it is
      found that significant inverse relation exists between linear gingival erythema,
      necrotizing ulcerative periodontitis, and CD 4 counts, but only in nondrug users.
      CONCLUSION: An inverse correlation between linear gingival erythema, necrotizing
      ulcerative periodontitis, and CD 4 counts in NIVDU indicating their reliability
      as a marker for immune suppression. Periodontitis is more prevalent among drug
      users indicating some difference in disease expression among the groups.

PMID- 22960975
TI  - Jejuno-ileal atresia: a 2-year preliminary study on presentation and outcome.
AB  - BACKGROUND/AIM: Intestinal atresia is a common cause of neonatal intestinal
      obstruction. Jejuno-ileum is the commonest site of intestinal atresia. Reports on
      Jejunoileal atresia in developing countries are still few. The purpose of this
      study is to determine the presentation and management outcomes of neonates with
      Jejunoileal atresia treated in our hospital. MATERIALS AND METHODS: Detailed data
      on all babies that presented and were treated within the study period
      (November2008-November, 2010) were kept and analyzed. A management protocol was
      put up and maintained. RESULT: A total of 9 babies (7males and 2 females) were
      treated. They were aged 2 hours to 13 days. Their weight ranged from 1.7kg to
      3.3kg. Apart from one baby which presented within 2hrs with prenatal ultrasound
      diagnosis, others had bilious vomiting from the first day of birth, abdominal
      distension and delayed or absent passage of meconium. Even though symptoms
      developed on the first day of birth, presentation to the surgical unit was
      delayed 72hours and beyond in most patients.Type I atresia is commonest
      (no=4).There is associated gut malrotation in 2 babies. Five babies had
      complications which included surgical site infection, sepsis, prolonged vomiting
      post operatively, aspiration, rupture of dilated proximal segment after membrane
      excision, entero-cutaneous fistula and malnutrition. Three babies died giving a
      mortality of 33.3%. Mortality is commoner in types IIIb and IV. CONCLUSION:
      Mortality is higher in complex atresia which most times will require neonatal
      intensive care and parenteral nutrition facilities. These are still lacking in
      our institution. Providing these facilities will further improve outcome.

PMID- 22960976
TI  - Vaginal myomectomy of a prolapsed gangrenous cervical leiomyoma.
AB  - We report a challenging case of a huge gangrenous prolapsed cervical leiomyoma in
      a multiparous HIV positive lady. A 37-year-old para 3 lady presented with a
      progressively increasing irreducible mass protruding out per vaginam, 3 months
      duration of heavy menses, and symptoms of a urinary tract infection. We performed
      a vaginal myomectomy and she did well postoperatively. A prolapsed gangrenous
      cervical leiomyoma is a rare condition with only a few cases reported in the
      literature. Vaginal myomectomy for this condition can be performed in experienced
      hands without difficulties.

PMID- 22960977
TI  - Cysticercosis presenting as cervical lymphadenopathy: a rare presentation in two
      cases with review of literature.
AB  - Lymphadenopathy is a rare mode of presentation of cysticercus infestation. Hence,
      in endemic areas, cysticercosis must be included in the differential diagnosis of
      superficial palpable swellings in the neck region. We report two cases of
      cervical lymphadenopathy which were clinically suspected to be of tuberculous
      etiology. However, fine-needle aspiration cytology (FNAC) revealed features of
      parasitic lymphadenitis consistent with cysticercosis. Our cases highlight the
      importance of FNAC as an initial and rapid diagnostic modality for detecting
      parasitic lesions manifesting as lymphadenitis. Diagnosis by the minimally
      invasive FNA technique prompted an early therapeutic intervention with good
      response in our patients.

PMID- 22960978
TI  - Marfan syndrome: report of two cases with review of literature.
AB  - Marfan syndrome is a variable, autosomal dominant disorder of connective tissue
      whose cardinal features affect the cardiovascular system, eyes and skeleton. The
      minimal birth incidence is around 1 in 9800. About three quarters of patients
      have an affected parent; new mutations account for the remainder. The patient's
      prognosis depends on the severity of cardiovascular complications and is mainly
      determined by progressive dilation of the aorta. If signs of Marfan syndrome are
      recognized, it is important to refer to the correct health care professional for
      further testing to prevent associated complications. If not properly treated,
      premature death may be caused by the severe cardiovascular and pulmonary
      complications associated with Marfan syndrome. Therefore, it is important to
      identify this potentially life-threatening condition in general practice. This
      article reports two cases with a very typical features of Marfan syndrome.

PMID- 22960979
TI  - Severe traumatic brain injury managed with decompressive craniectomy.
AB  - Patients with severe traumatic brain injury may develop intractable raised ICP
      resulting in high mortality and morbidity. This may be anticipated from the
      patient's clinical status and imaging findings even where intracranial monitoring
      is unavailable. Outcome may be improved by early and aggressive control of ICP
      and surgical decompressive craniectomy is increasingly advocated as necessary.

PMID- 22960980
TI  - Laparoscopic partial nephrectomy is less morbid than open surgery.

PMID- 22960981
TI  - Autoimmune disorders in patients with idiopathic thrombotic thrombocytopenic
      purpura.
AB  - 76 German patients suffering from thrombotic thrombocytopenic purpura (TTP) were
      interrogated about the prevalence of co-occurring autoimmune disorders. In order
      to analyze a possible association of TTP with the questioned diseases, a
      comparison of prevalence rates between the patient group and the general
      population has been made for each disease. RESULTS: Compared to the estimated
      prevalence rates, the statistical analysis revealed an unexpected high occurrence
      of the following disorders within the patient group: Hashimoto's thyroiditis
      (23.5% within the patients compared to 0.7% within the general population,
      p<0.001), systemic lupus erythematosus (SLE) (6.5% in patients to 0.025% in the
      general population, p<0.001), immune thrombocytopenic purpura (ITP) (6.3% in
      patients to 0.02% in the general population, p<0.001), psoriasis (9.4% in
      patients to 2.5% in the general population, p=0.005) and celiac disease (3.1% in
      patients to 0.2% in the general population, p=0.007). CONCLUSION: These findings
      confirm the mentioned tendency of autoimmune diseases to co-occur in one
      individual and argue once more for a genetic susceptibility in idiopathic TTP as
      well as in autoimmune disorders.

PMID- 22960982
TI  - Thirteen years of antibiotic susceptibility surveillance of Pseudomonas
      aeruginosa from intensive care units and urology services in the Netherlands.
AB  - The purpose of this study was the evaluation of trends in the antimicrobial
      resistance of Pseudomonas aeruginosa from intensive care unit (ICU) patients and
      urology patients in the Netherlands. From 1998 to 2010, 1,927 consecutive P.
      aeruginosa isolates from ICU (n = 1,393) and urology service patients (n = 534)
      of 14 university and referral hospitals all over the Netherlands were collected
      and their susceptibility to relevant antibiotics was determined according to the
      European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.
      Over time, a significant upward trend in the resistance of P. aeruginosa strains
      collected from ICUs to piperacillin (1.2 % to 10.6 %, p = 0.0175), piperacillin
      tazobactam (1.2 % to 12.1 %, p = 0.0008), ceftazidime (1.2 % to 7.8 %, p =
      0.0064), cefepime (4.8 % to 6.4 %, p = 0.0166), imipenem (6 % to 19.1 %, p <
      0.0001), meropenem (8.3 % to 17 %, p = 0.0022) and ciprofloxacin (13.1 % to 31.2
      %, p = 0.0024) was observed, as was the prevalence of multi-resistance (1.2 % to
      8.5 %, p = 0.0002). For P. aeruginosa isolates from the urology services, the
      resistance to imipenem increased (4.1 % to 7.8 %, p = 0.0006) and to
      ciprofloxacin it decreased (22.4 % to 18.8 %, p = 0.025). Like in other
      countries, in the Netherlands, an increase in multi-resistant Gram-negatives is
      observed, suggesting the presence and dissemination of several mechanisms of
      resistance. Our findings emphasise the importance of local surveillance for the
      setting up of local antibiotic guidelines and to support optimal empiric therapy.
      With the observed increase in multi-resistance, the direct testing of alternative
      antibiotics like polymyxins and fosfomycin is essential. Our data also illustrate
      the importance of adequate outbreak control measures.

PMID- 22960983
TI  - What you don't know can hurt you; early asymptomatic lung disease in cystic
      fibrosis.

PMID- 22960985
TI  - Phase II tailored S-1 regimen study of first-line chemotherapy in elderly
      patients with advanced and recurrent non-small cell lung cancer.
AB  - PURPOSE: We investigated the efficacy and toxicity of a novel oral 5-fluorouracil
      (5-FU) formulation (S-1), administered according to a tailored dose regimen.
      METHODS: S-1 was administered orally for 28 days, followed by 14 days of no
      treatment, in 23 patients who received a tailored dose of S-1, adjusted on the
      basis of individual creatinine clearance and body surface area. In 8 of the
      patients, pharmacokinetic study was performed on the 6 points on 7th day after S
      1 administration. RESULTS: Of the 23 patients enrolled in this study, 2 (8.7 %)
      had a partial response and 14 (60.9 %) had stable disease. The disease control
      rate was 69.6 % (16/23) (95 % confidence interval, 50.8-88.4 %). Grade 3/4
      hematologic and non-hematologic toxicities were minor. In the pharmacokinetic
      study group, the maximum plasma concentration (C (max)) and the area under the
      plasma concentration curve of 5-FU at all 6 points after administration of the
      tailored S-1 dose regimen were similar to the values reported in a previous study
      describing cancer patients with normal renal function who received a standard
      dose of S-1 (80 mg/m(2)/day). CONCLUSIONS: Our results suggest that tailored S-1
      monotherapy is safe and therapeutically useful as first-line treatment for
      elderly patients with advanced and recurrent non-small cell lung cancer.

PMID- 22960986
TI  - Movement disorders: what lies beneath?

PMID- 22960984
TI  - Progress in cystic fibrosis and the CF Therapeutics Development Network.
AB  - Cystic fibrosis (CF), the most common life-shortening genetic disorder in
      Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the
      Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network
      (CF-TDN) as a central element of its Therapeutics Development Programme. Designed
      to accelerate the clinical evaluation of new therapies needed to fulfil the CFF
      mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since
      its inception, and has contributed to studies as varied as initial safety and
      proof of concept trials to pivotal programmes required for regulatory approval.
      This review highlights recent and significant research efforts of the CF-TDN,
      including a summary of contributions to studies involving CF transmembrane
      conductance regulator (CFTR) modulators, airway surface liquid hydrators and
      mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies.
      Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals
      of the network, are also summarised.

PMID- 22960987
TI  - The clinical features of pathologically confirmed vascular parkinsonism.
AB  - OBJECTIVE: To evaluate in detail the clinical features in a large series of
      pathologically confirmed cases of vascular Parkinsonism (VP). BACKGROUND: In the
      absence of widely accepted diagnostic criteria for VP pathological confirmation
      of diagnosis is necessary to ensure diagnostic reliability, and has only been
      reported in a few small series. DESIGN/METHODS: The archival records of the Queen
      Square Brain Bank (QSBB) have been used to identify cases of Parkinsonism where
      cerebrovascular disease was the only pathological finding. Clinical notes were
      scrutinised and milestones of disease progression were compared with other
      atypical Parkinsonian syndromes from previous QSBB studies. RESULTS: Twenty-eight
      cases were included. Mean age of onset and disease duration were 70.6 (SD+/-
      6.42) and 10.5 (SD+/- 66.1) years respectively. Bradykinesia was present in all
      cases, rigidity in 96%, falls in 76%, pyramidal signs in 54%, urinary
      incontinence in 50% and dementia in 39%.Visual hallucinations in 0%. Two-thirds
      had an insidious onset and a relentless rather than stepwise progression of
      disability. When compared with other Parkinsonian syndromes, VP had an older age
      of onset. CONCLUSIONS: In comparison with other Parkinsonian syndromes the
      patients were older and had an extremely low frequency of visual hallucinations
      compared with Parkinson's disease.

PMID- 22960988
TI  - Match play intensity distribution in youth soccer.
AB  - The purpose of this study was to quantify match play intensity distribution in
      young soccer players in relation to age, playing position and physical fitness.
      Distance covered and heart rate were measured (global positioning system) on 103,
      highly-trained young players (Under13 to Under 18) during 42 international club
      games. Maximal sprinting speed (MSS), estimated maximal aerobic speed (MAS) and
      maximal heart rate (HRmax) were assessed via field test measures. Distance
      covered and heart rate (HR) were categorized into 5 intensity zones relative to
      MSS and MAS and HR(max), respectively. Intensity distribution was significantly
      influenced by both age and playing position with younger groups, wide-midfielders
      and strikers covering the greatest distance above the MAS. There was a
      significant, negative, large-to-very large correlation (r= -0.52-0.74) between
      MAS and the distance run at speeds above MAS for all positions except strikers.
      HR responses were not different across age groups and playing positions. Distance
      covered below MAS were lower in the second half for all positions (P<0.05;
      0.08<eta(2)<0.20), while distance covered at intensities above MAS were
      maintained (P>0.1; 0.00<eta(2)<0.03). This reduction in distance covered below
      MAS was not related to a player's physical capacity. Except for strikers, a
      superior aerobic fitness level was unlikely to affect total distance covered but
      was associated with a reduced individual running demand during the game.

PMID- 22960989
TI  - IGF-1 response to arm exercise with eccentric and concentric muscle contractions
      in resistance-trained athletes with left ventricular hypertrophy.
AB  - The study aimed at evaluating changes in plasma levels of insulin-like growth
      factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3),
      testosterone, growth hormone (GH), cortisol, and insulin in resistance-trained
      male athletes with (n=9) and without (n=9) left ventricular hypertrophy (LVH) in
      response to eccentric (ECC) and concentric (CON) arm exercise. 10 age-matched
      healthy non-trained subjects served as controls. M-mode and 2D Doppler
      echocardiography were used to estimate LV mass.Resting IGF-1 concentration was
      higher in LVH athletes compared to controls (52 +/- 5 nM vs. 46 +/- 7 nM,
      p<0.05). ECC exercise resulted in higher (p<0.05) serum IGF-1 concentrations in
      athletes with LVH (70 +/- 11 nM, n=9) compared to those without LVH (62 +/- 10
      nM, n=9), and to untrained controls (54 +/- 6 nM). Both CON and ECC exercise
      resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242
      +/- 57 and 274 +/- 58, athletes, vs. 215 +/- 63 and 244 +/- 67, controls, nM,
      p<0.05). In ECC exercise, GH concentrations were lower in LVH than in non-LVH
      athletes (4.7 +/- 2.1 vs. 6.1 +/- 1.8 ng  mL(-1), p<0.05). No differences in
      other hormones were found between groups. In conclusion, LVH is accompanied by
      elevated resting serum IGF-1 and enhanced response to eccentric arm exercise.
      These findings suggest a role of IGF-1, possibly released from contracting
      muscle, in stimulating LV hypertrophy in resistance training.

PMID- 22960990
TI  - Content validity of the Rodeo-SCAT.
AB  - The purpose of this study was to establish the content validity of the Rodeo SCAT
      for the sport of rodeo and bull riding. The study design was comprised of expert
      consensus and content validation. A modified Ebel procedure was employed to
      content validate the rodeo SCAT. Content validation using this method includes
      experts agreeing on the importance of each item that comprises the rodeo SCAT.
      This 3-stage process involved: 1) face validation by a local committee: 2)
      initial expert consensus measurement via distance; and 3) a face-to-face
      discussion for items that did not originally achieve 80% consensus of the group.
      Experts were chosen from the Canadian Professional Rodeo Sport Medicine Team
      (Canada) and the Justin Sports Medicine Team (USA). 27 out of a total possible 68
      items achieved 80% consensus in the second stage. In the third stage, 4 of the 68
      items were removed with consensus from the expert group. All remaining items
      achieved 80% consensus for inclusion. In summary, the rodeo SCAT is content valid
      and thus, appropriate for use in the sport of rodeo context or environment.

PMID- 22960991
TI  - Motor control and low back pain in dancers.
AB  - Professional dancers suffer a high incidence of injuries, especially to the spine
      and lower extremities. There is a lack of experimental research addressing low
      back pain (LBP) in dancers. The aim of this study is to compare lumbopelvic motor
      control, muscle extensibility and sacroiliac joint pain between dancers with and
      without a history of LBP. 40 pre-professional dancers (mean age of 20.3 years)
      underwent a clinical test battery, consisting of an evaluation of lumbopelvic
      motor control, muscle extensibility, generalized joint hypermobility, and
      sacroiliac joint pain provocation tests. Also self-reported measurements and
      standardized questionnaires were used. 41% of the dancers suffered from LBP
      during at least 2 consecutive days in the previous year. Only one dancer suffered
      from sacroiliac joint pain. Compared to dancers without a history of LBP, dancers
      with a history of LBP showed poorer lumbopelvic motor control (p<0.05). No
      differences in muscle extensibility or joint hypermobility were observed between
      dancers (p>0.05). Despite their young age, pre-professional dancers suffer from
      LBP frequently. Sacroiliac joint pain, generalized joint hypermobility or muscle
      extensibility appears unrelated to LBP in dancers. Motor control is decreased in
      those with a history of LBP. Further research should examine whether motor
      control is etiologically involved in LBP in dancers.

PMID- 22960992
TI  - Salivary nitric oxide and alpha-amylase as indexes of training intensity and
      load.
AB  - This study examined the variation in salivary nitric oxide (NO), alpha-amylase
      (sAA) and serum markers of muscle injury during 21 weeks of training in elite
      swimmers. Samples of saliva and blood were collected once a month during 5 months
      from 11 male professional athletes during their regular training season. The
      variation in each marker throughout the 21 weeks was compared with the dynamics
      of training volume, intensity and load. Unstimulated whole saliva was assessed
      for NO and sAA whereas venous blood was assessed for lactate dehydrogenase,
      creatine kinase, and gamma-glutamyltransferase. Nitric oxide and sAA showed a
      proportional response to the intensity of training. However, whereas the
      concentration of NO increased across the 21 weeks, the activity of sAA decreased.
      Similar variations in the concentration of NO and the markers of muscle injury
      were also observed. The higher concentration of NO might be attributed to changes
      in haemodynamics and muscle regenerative processes. On the other hand, autonomic
      regulation towards parasympathetic predominance might have been responsible for
      the decrease in sAA activity. These findings provide appealing evidence for the
      utilization of salivary constituents in sports medicine to monitor training
      programmes.

PMID- 22960993
TI  - Low-volume liquid delivery and nanolithography using a nanopipette combined with
      a quartz tuning fork-atomic force microscope.
AB  - Electric-field-induced low-volume liquid ejection under ambient conditions was
      realized at a low bias potential of 12 V via a nanopipette (aperture diameter of
      30 nm) combined with a non-contact, distance-regulated (within 10 nm) quartz
      tuning fork-atomic force microscope. A capillary-condensed water meniscus,
      spontaneously formed in the tip-substrate nanogap, reduces the ejection barrier
      by four orders of magnitude, facilitating nanoliquid ejection and subsequent
      liquid transport/dispersion onto the substrate without contact damage from the
      pipette. A study of nanofluidics through a free-standing liquid nanochannel and
      nanolithography was performed with this technique. This is an important
      breakthrough for various applications in controlled nanomaterial-delivery and
      selective deposition, such as multicolor nanopatterning and nano-inkjet devices.

PMID- 22960994
TI  - Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with
      head and neck tumors undergoing radiotherapy treatment alone or in combination
      with chemotherapy.
AB  - OBJECTIVE: To describe the oropharyngeal candidiasis (OPC) prevalence in Spanish
      patients with head and neck cancer undergoing radiotherapy, alone or combined
      with chemotherapy. Secondary objectives were to determine the prevalence of
      Candida species colonization, and to explore whether different Candida species
      colonizing the oral cavity and the treatment were associated with a higher
      prevalence of OPC. METHODS: This is an observational, cross-sectional,
      multicentre study, conducted in Spanish radiation oncology units. Patients were
      diagnosed with head and neck cancer and started a radiotherapy treatment alone or
      combined with chemotherapy at the moment of their inclusion (N = 92). RESULTS:
      The OPC prevalence was 26 %. The identification of colonizing pathogens was
      performed in 49 patients, and Candida albicans was the dominant yeast (69 %),
      while non-albicans Candida was only found in 15 patients (31 %). Patients with C.
      albicans colonization had a significant higher prevalence of OPC compared to
      patients colonized by non-albicans Candida (p = 0.0273), but no difference was
      found regarding the OPC prevalence in patients receiving only radiotherapy
      compared to patients with both radiotherapy and chemotherapy treatments.
      CONCLUSIONS: Our data represent a step further in the knowledge of Candida
      species present in Spanish patients with head and neck tumors under radiation
      therapy. This is an essential step to manage the prophylaxis and treatment of
      OPC, since it might lead to severe clinical complications causing treatment
      interruption and, thus, representing a reduction in anti-tumor efficacy.

PMID- 22960995
TI  - Lysine methylation strategies for characterizing protein conformations by NMR.
AB  - In the presence of formaldehyde and a mild reducing agent, reductive methylation
      is known to achieve near complete dimethylation of protein amino groups under non
      denaturing conditions, in aqueous media. Amino methylation of proteins is
      employed in mass spectrometric, crystallographic, and NMR studies. Where
      biosynthetic labeling is prohibitive, amino (13)C-methylation provides an
      attractive option for monitoring folding, kinetics, protein-protein and protein
      DNA interactions by NMR. Here, we demonstrate two improvements over traditional
      (13)C-reductive methylation schemes: (1) By judicious choice of stoichiometry and
      pH, epsilon-aminos can be preferentially monomethylated. Monomethyl tags are less
      perturbing and generally exhibit improved resolution over dimethyllysines, and
      (2) By use of deuterated reducing agents and (13)C-formaldehyde, amino groups can
      be labeled with (13)CH(2)D tags. Use of deutero-(13)C-formaldehyde affords either
      (13)CHD(2), or (13)CD(3) probes depending on choice of reducing agent. Making use
      of (13)C-(2)H scalar couplings, we demonstrate a filtering scheme that eliminates
      natural abundance (13)C signal.

PMID- 22960996
TI  - Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically
      disordered protein alpha-synuclein.
AB  - Intrinsically disordered proteins (IDPs) are abundant in nature and
      characterization of their potential structural propensities remains a widely
      pursued but challenging task. Analysis of NMR secondary chemical shifts plays an
      important role in such studies, but the output of such analyses depends on the
      accuracy of reference random coil chemical shifts. Although uniform
      perdeuteration of IDPs can dramatically increase spectral resolution, a feature
      particularly important for the poorly dispersed IDP spectra, the impact of
      deuterium isotope shifts on random coil values has not yet been fully
      characterized. Very precise (2)H isotope shift measurements for (13)C(alpha),
      (13)C(beta), (13)C', (15)N, and (1)H(N) have been obtained by using a mixed
      sample of protonated and uniformly perdeuterated alpha-synuclein, a protein with
      chemical shifts exceptionally close to random coil values. Decomposition of these
      isotope shifts into one-bond, two-bond and three-bond effects as well as intra-
      and sequential residue contributions shows that such an analysis, which ignores
      conformational dependence, is meaningful but does not fully describe the total
      isotope shift to within the precision of the measurements. Random coil (2)H
      isotope shifts provide an important starting point for analysis of such shifts in
      structural terms in folded proteins, where they are known to depend strongly on
      local geometry.

PMID- 22960997
TI  - 3D-TROSY-based backbone and ILV-methyl resonance assignments of a 319-residue
      homodimer from a single protein sample.
AB  - The feasibility of practically complete backbone and ILV methyl chemical shift
      assignments from a single [U-(2)H,(15)N,(13)C; Iledelta1-{(13)CH(3)}; Leu,Val
      {(13)CH(3)/(12)CD(3)}]-labeled protein sample of the truncated form of ligand
      free Bst-Tyrosyl tRNA Synthetase (Bst-DeltaYRS), a 319-residue predominantly
      helical homodimer, is established. Protonation of ILV residues at methyl
      positions does not appreciably detract from the quality of TROSY triple resonance
      data. The assignments are performed at 40  degrees C to improve the sensitivity
      of the measurements and alleviate the overlap of (1)H-(15)N correlations in the
      abundant alpha-helical segments of the protein. A number of auxiliary approaches
      are used to assist in the assignment process: (1) selection of (1)H-(15)N amide
      correlations of certain residue types (Ala, Thr/Ser) that simplifies 2D (1)H
      (15)N TROSY spectra, (2) straightforward identification of ILV residue types from
      the methyl-detected 'out-and-back' HMCM(CG)CBCA experiment, and (3) strong
      sequential HN-HN NOE connectivities in the helical regions. The two subunits of
      Bst-YRS were predicted earlier to exist in two different conformations in the
      absence of ligands. In agreement with our earlier findings (Godoy-Ruiz in J Am
      Chem Soc 133:19578-195781, 2011), no evidence of dimer asymmetry has been
      observed in either amide- or methyl-detected experiments.

PMID- 22960998
TI  - The effect of genetic polymorphisms in UGT2B15 on the pharmacokinetic profile of
      sipoglitazar, a novel anti-diabetic agent.
AB  - PURPOSE: Sipoglitazar was a novel, azolealkanoic acid derivative that possesses
      selective activity for the peroxisome proliferator-activated receptors (PPAR)
      PPARgamma, PPARalpha, and PPARdelta. The compound undergoes phase II
      biotransformation by conjugation catalyzed by UDP-glucuronosyltransferase (UGT).
      The aim of this analysis was to explore the influence of genetic polymorphism in
      UGT on the pharmacokinetics of sipoglitazar. METHODS: Three preliminary phase I
      clinical pharmacology studies were conducted in tandem in healthy human subjects.
      Genotyping was undertaken in a total of 82 subjects in the phase I program for
      the purpose of genotyping UGT polymorphisms. Plasma samples were collected for up
      to 48 h post-dose to characterize the pharmacokinetic profile following a single
      oral dose of the drug. RESULTS: Plasma concentrations of sipoglitazar and the
      distribution of dose-normalized individual values for area under the plasma
      concentration-time curve from time 0 to infinity (AUC(0-infinity)) before any
      stratification were considerably skewed with a multi-modal distribution. The
      proportion of variability in AUC(0-infinity) explained by UGT2B15 was 66.7 % (P <
      0.0001); the addition of other genetic or demographic factors was not
      statistically significant. Subjects homozygous for the UGT2B15 D85Y variant
      (UGT2B15*2/*2) were exposed to greater plasma concentrations of sipoglitazar than
      subjects homozygous for the wild-type allele UGT2B15*1/*1 (3.26-fold higher) or
      heterozygous allele UGT2B15*1/*2 (2.16-fold higher). CONCLUSIONS: These results
      indicate that sipoglitazar clearance is substantially modified by UGT2B15 enzyme
      variants, with higher exposure observed in the UGT2B15*2/*2 genotype group.

PMID- 22960999
TI  - Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese
      identify multiple susceptibility loci and gene-environment interactions.
AB  - We conducted a genome-wide association study (GWAS) and a genome-wide gene
      environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in
      2,031 affected individuals (cases) and 2,044 controls with independent validation
      in 8,092 cases and 8,620 controls. We identified nine new ESCC susceptibility
      loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and
      18p11, had a significant marginal effect (P=1.78*10(-39) to P=2.49*10(-11)) and
      two of which, at 2q22 and 13q33, had a significant association only in the gene
      alcohol drinking interaction (gene-environment interaction P (PG*E)=4.39*10(-11)
      and PG*E=4.80*10(-8), respectively). Variants at the 4q23 locus, which includes
      the ADH cluster, each had a significant interaction with alcohol drinking in
      their association with ESCC risk (PG*E=2.54*10(-7) to PG*E=3.23*10(-2)). We
      confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint
      analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a
      fourfold increased risk for ESCC compared to drinkers without these risk alleles.
      Our results underscore the direct genetic contribution to ESCC risk, as well as
      the genetic contribution to ESCC through interaction with alcohol consumption.

PMID- 22961003
TI  - [Severe organic dysphagia after long-term ventilation in a patient with sepsis
      and multiorgan failure].
AB  - A case of severe chronic dysphagia lasting more than 1 year after long-term
      ventilation due to sepsis is presented. Fiber optic endoscopic examination of
      swallowing (FEES) revealed retention of food on both sides of the base of the
      tongue and in both valleculae combined with severe penetration and postglutitive
      aspiration into the larynx. The reason was a broad-based scarred adhesion between
      the lingual side of the epiglottis and the tongue base. The adhesion was resected
      using a CO(2) laser. The final examination 3 months later showed complete
      recovery of normal swallowing function.

PMID- 22961002
TI  - Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.
AB  - Inherited peripheral neuropathies are frequent neuromuscular disorders known for
      their clinical and genetic heterogeneity. In 33 families, we identified 8
      mutations in HINT1 (encoding histidine triad nucleotide-binding protein 1) by
      combining linkage analyses with next-generation sequencing and subsequent cohort
      screening of affected individuals. Our study provides evidence that loss of
      functional HINT1 protein results in a distinct phenotype of autosomal recessive
      axonal neuropathy with neuromyotonia.

PMID- 22961004
TI  - [Enrolment of intensive care patients in clinical studies. Ethical, legal and
      organizational problems from an interdisciplinary point of view].
AB  - Nowadays, most patients in hospital die in the intensive care unit from sepsis
      and multiple organ failure. Clinical research in this critically ill and
      vulnerable patient population bears a lot of ethical and legal problems; however,
      it remains a must in order to develop evidence-based diagnostic and therapeutic
      strategies for life-threatening diseases with special respect to limited health
      care resources. With regard to the Declaration of Helsinki, good clinical
      practice guidelines (GCP) from the European Medicines Agency (EMA) and the German
      medical drug law (AMG) this article discusses ethical and legal aspects of
      patient inclusion for clinical trials as well as incentives for appropriate
      patient recruitment from an interdisciplinary point of view.

PMID- 22961005
TI  - Identifying a high-risk cohort in a complex and dynamic risk environment: out-of
      bounds skiing--an example from avalanche safety.
AB  - The development of effective prevention initiatives requires a detailed
      understanding of the characteristics and needs of the target audience. To
      properly identify at-risk individuals, it is crucial to clearly delineate risky
      from acceptable behavior. Whereas health behavior campaigns commonly use single
      conditions (e.g., lack of condom use) to identify high-risk cohorts, many risk
      behaviors are more complex and context dependent, rendering a single condition
      approach inadequate. Out-of-bounds skiing, an activity associated with voluntary
      exposure to avalanche hazard, is an example of such a multifaceted risk-taking
      activity. Using a dataset from an extensive online survey on out-of-bounds
      skiing, we present an innovative approach for identifying at-risk individuals in
      complex risk environments. Based on a risk management framework, we first examine
      risk-taking preferences of out-of-bounds skiers with respect to exposure and
      preparedness--the two main dimensions of risk management--separately. Our
      approach builds on existing person-centered research and uses Latent Class
      Analysis to assign survey participants to mutually exclusive behavioral classes
      on these two dimensions. Discrete Choice Experiments are introduced as a useful
      method for examining exposure preferences in the context of variable external
      conditions. The two class designations are then combined using a risk matrix to
      assign overall risk levels to each survey participant. The present approach
      complements existing person-centered prevention research on the antecedents of
      risk-taking by offering a process-oriented method for examining behavioral
      patterns with respect to the activity itself. Together, the two approaches can
      offer a much richer perspective for informing the design of effective prevention
      initiatives.

PMID- 22961001
TI  - Common variants at the MHC locus and at chromosome 16q24.1 predispose to
      Barrett's esophagus.
AB  - Barrett's esophagus is an increasingly common disease that is strongly associated
      with reflux of stomach acid and usually a hiatus hernia, and it strongly
      predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor
      prognosis. We report the first genome-wide association study on Barrett's
      esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage
      and 5,986 cases and 12,825 controls in the replication stage. Variants at two
      loci were associated with disease risk: chromosome 6p21, rs9257809
      (Pcombined=4.09*10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13
      1.28), within the major histocompatibility complex locus, and chromosome 16q24,
      rs9936833 (Pcombined=2.74*10(-10); OR=1.14, 95% CI=1.10-1.19), for which the
      closest protein-coding gene is FOXF1, which is implicated in esophageal
      development and structure. We found evidence that many common variants of small
      effect contribute to genetic susceptibility to Barrett's esophagus and that SNP
      alleles predisposing to obesity also increase risk for Barrett's esophagus.

PMID- 22961000
TI  - Dense fine-mapping study identifies new susceptibility loci for primary biliary
      cirrhosis.
AB  - We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC
      Consortium and 8,514 UK population controls across 196,524 variants within 186
      known autoimmune risk loci. We identified 3 loci newly associated with PBC (at
      P<5*10(-8)), increasing the number of known susceptibility loci to 25. The most
      associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further
      implicating JAK-STAT and cytokine signaling in disease pathogenesis. An
      additional five loci contained nonsynonymous variants in high linkage
      disequilibrium (LD; r2>0.8) with the most associated variant at the locus. We
      found multiple independent common, low-frequency and rare variant association
      signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA)
      signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin
      regions in high LD (r2>0.8) with the most associated variant. This study shows
      how data from dense fine-mapping arrays coupled with functional genomic data can
      be used to identify candidate causal variants for functional follow-up.

PMID- 22961006
TI  - The effect of enteral supplementation of specific neutral and acidic
      oligosaccharides on the faecal microbiota and intestinal microenvironment in
      preterm infants.
AB  - We aimed to determine the effects of enteral supplementation of a prebiotic
      mixture of neutral and acidic oligosaccharides (scGOS/lcFOS/pAOS) on the faecal
      microbiota and microenvironment in preterm infants. Furthermore, we determined
      the influence of perinatal factors on the development of the faecal microbiota.
      In a randomised controlled trial, preterm infants with gestational age <32 weeks
      and/or birth weight <1,500 g received enteral supplementation of scGOS/lcFOS/pAOS
      or placebo (maltodextrin) between days 3 and 30 of life. Faecal microbiota, as
      measured with fluorescent in situ hybridisation (FISH), and microenvironment
      [short-chain fatty acids (SCFAs), pH, sIgA] were measured at four time points:
      before the start of the study and at days 7, 14 and 30 of life. In total, 113
      preterm infants were included. Enteral supplementation of the prebiotic mixture
      increased the total bacteria count at day 14 (Exp 3.92; 95 % confidence interval
      [CI] 1.18-13.04, p = 0.03), but not at day 30 (Exp 1.73; 95 % CI 0.60-5.03, p =
      0.31). There was a trend toward increased bifidobacteria counts. There was a
      delayed intestinal colonisation of all bacteria. Enteral supplementation of the
      prebiotic mixture decreased the faecal pH (Exp 0.71; 95 % CI 0.54-0.93, p = 0.01)
      and there was a trend toward increased acetic acid compared to the placebo group
      (Exp 1.09; 95 % CI 0.99-1.20, p = 0.10). There was no effect on sIgA (Exp 1.94;
      95 % CI 0.28-13.27, p = 0.50). Antibiotics decreased the total bacteria count
      (Exp 0.13; 95 % CI 0.08-0.22, p < 0.001). Enteral supplementation of a prebiotic
      mixture of neutral and acidic oligosaccharides increases the postnatal intestinal
      colonisation. However, the extensive use of broad-spectrum antibiotics in preterm
      infants decreased the growth of all intestinal microbiota, thereby, delaying the
      normal microbiota development.

PMID- 22961007
TI  - Seroreactivity for spotted fever rickettsiae and co-infections with other tick
      borne agents among habitants in central and southern Sweden.
AB  - Patients seeking medical care with erythema migrans or flu-like symptoms after
      suspected or observed tick bite in the southeast of Sweden and previously
      investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined
      for serological evidence of rickettsial infection (Study 1). Twenty of 206
      patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than
      the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion
      indicative of recent or current infection and 13 patients had titres compatible
      with past infection, of which five patients were judged as probable infection. Of
      19 patients with medical records, 11 were positive for Borrelia spp. as well, and
      for Anaplasma sp., one was judged as positive. Five of the 19 patients had
      antibodies against all three pathogens. Erythema migrans or rash was observed at
      all combinations of seroreactivity, with symptoms including fever, muscle pain,
      headache and respiratory problems. The results were compared by screening an
      additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia
      spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for
      Rickettsia spp., of which five were judged as recent or current infection.
      Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors
      without clinical symptoms, approximately 1 % were seroreactive for Rickettsia
      spp., interpreted as past infection. The study shows that both single and co
      infections do occur, which illustrate the complexity in the clinical picture and
      a need for further studies to fully understand how these patients should best be
      treated.

PMID- 22961008
TI  - Deficiency of the oxygen sensor PHD1 augments liver regeneration after partial
      hepatectomy.
AB  - PURPOSE: Liver regeneration after partial hepatectomy (PH) occurs in conditions
      of reduced oxygen supply. HIF prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3)
      are oxygen sensors involved in adaptive response to hypoxia. Specific functions
      of these PHD enzymes in liver regeneration have, however, remained enigmatic.
      Here, we investigated the significance of PHD1 in liver regeneration following
      hepatectomy. METHODS: Liver regeneration was studied in PHD1-deficient (PHD1(-/
      )) and wild type (WT) mice subjected to 80% hepatectomy. For in vitro analyses,
      hepatocytes were isolated from PHD1(-/-) and WT livers. Cell cycle progression
      was studied via FACS-based analysis of nuclear DNA profile. Transcription factor
      binding assays, qRT-PCR, and immunoblotting were applied to study the relevance
      of PHD1 downstream effectors during liver regeneration. RESULTS: Liver
      regeneration was significantly enhanced in PHD1(-/-) mice compared to WT
      littermates. This effect was due to enhanced proliferation rather than to
      hypertrophy of liver cells. Cell cycle progression was significantly enhanced,
      and transcriptional activity of the cell cycle regulator c-Myc was increased in
      PHD1-deficient hepatocytes. These changes coincided with increased expression of
      cyclin D2, a cell cycle-promoting c-Myc target, and decreased expression of the
      cell cycle-delaying c-Myc target p21. CONCLUSIONS: Loss of PHD1 enhances liver
      regeneration by boosting hepatocyte proliferation in a c-Myc-dependent fashion.
      PHD1 might, therefore, represent a potential target to facilitate liver
      regeneration after surgical resection.

PMID- 22961009
TI  - Transcriptional regulation of desaturase genes in Pichia pastoris GS115.
AB  - Here we investigated the regulation of Pichia pastoris desaturase genes by low
      temperature and exogenous fatty acids in the late-exponential phase at the
      transcriptional level. Time-course studies of gene expression showed that mRNA
      levels of four desaturase genes were rapidly and transiently enhanced by low
      temperature and suppressed by exogenous oleic acid. Stearic acid showed no
      obvious repression of mRNA levels of Fad12 and Fad15 and a slight increase in
      Fad9A and Fad9B mRNA levels. Using a promoter-reporter gene construct, we
      demonstrated that the pFAD15 promoter activity was induced by low temperature in
      a time-dependent manner and reduced in a dose- and time-dependent manner by
      unsaturated fatty acids. Also, there was no absolute correlation between mRNA
      abundance and production of corresponding fatty acids. Disruption of Spt23
      resulted in a decrease in transcript levels of Fad9A and Fad9B, but had little
      effect on the other desaturase genes. Consistent with these observations, a
      decrease in the relative amount of oleic acid (OLA) and an increase in the
      relative content of linoleic acid and ALA with different degrees were clearly
      observed in the stationary phase cells of DeltaSpt23 mutant. Further analysis
      showed that the effect of low-temperature activation and OLA inhibition on
      expression of Fad9A and Fad9B seemed to disappear after disruption of the Spt23
      gene, which indicated that Spt23p is essential for the expression of two Delta9
      desaturase genes internally and probably involved in the regulation of Delta9
      desaturase genes transcription in response to external stimuli, and thereby plays
      a role in the synthesis of OLA.

PMID- 22961010
TI  - Basics and applications of stem cells in the pancreas.
AB  - Enormous efforts have been made to establish pancreatic stem/progenitor cells as
      a source for regenerative medicine for the treatment of diabetes mellitus. In
      recent years, it has been recognized that the self-renewal of beta cells is the
      dominant process involved in postnatal beta-cell regeneration and expansion.
      Nevertheless, several in-vitro studies have suggested that ductal or as yet
      unidentified cells are candidates for pancreatic stem/progenitor cells that can
      differentiate into multilineage cells, including insulin(+) cells. The question
      remains as to whether beta cells are generated postnatally from stem/progenitor
      cells other than pre-existing beta cells. Furthermore, mutated pancreatic stem
      cells are considered to be prospective candidates for cancer stem cells or tumor
      initiating cells. This review highlights recent progress in pancreatic
      stem/progenitor cell research.

PMID- 22961011
TI  - Pre-diagnostic alcohol consumption and postmenopausal breast cancer survival: a
      prospective patient cohort study.
AB  - Study results on the association of alcohol consumption with breast cancer
      survival are inconsistent, partly due to the use of different survival outcomes.
      We assessed the association of pre-diagnostic alcohol consumption with survival
      and recurrence in a prospective cohort study in Germany including 2,522
      postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed
      between 2001 and 2005 and vital status, causes of death, and recurrences were
      verified through the end of 2009. Cox proportional hazards models were stratified
      by age at diagnosis and study center and adjusted for relevant prognostic
      factors. Alcohol consumption was non-linearly associated with increased breast
      cancer-specific mortality [e.g., >=12 vs. <0.5 g/day: hazard ratio (HR) = 1.74,
      95 % confidence interval (CI): 1.13, 2.67]. Results were independent of estrogen
      receptor status. A non-significantly decreased risk of mortality due to other
      causes was found (>=12 vs. <0.5 g/day: HR = 0.67, 95 % CI: 0.35, 1.29). Alcohol
      consumption was not associated with overall mortality (>=12 vs. <0.5 g/day: HR =
      1.28, 95 % CI: 0.90, 1.81) and breast cancer recurrence (>=12 vs. <0.5 g/day: HR
      = 1.08, 95 % CI: 0.73, 1.58). In conclusion, our findings show that consumption
      of alcohol before diagnosis is non-linearly associated with increased breast
      cancer-specific mortality but may be associated with decreased risk of mortality
      due to other causes.

PMID- 22961012
TI  - Previous burn injury predisposes mice to lipopolysaccharide-induced changes in
      glucose metabolism.
AB  - In mice, it has been demonstrated that at 7 days after burn injury, injection of
      lipopolysaccharide (LPS) is more lethal than the same dose at 1 day after injury.
      In the present study, we examined the effect of LPS injection to mice burned 7
      days previously on glucose metabolism ([(18)F] 2-fluoro-2-deoxy-D-glucose
      [(18)FDG] uptake) in vivo. CD-1 male mice (25-28 g, Charles River Breeding
      Laboratories, Wilmington, MA) were anesthetized, backs shaven, and subjected to
      dorsal full thickness burn on 25% TBSA. Sham-treated animals were used as
      controls. Six days after burn injury, all mice were fasted overnight. One half of
      the burned and sham controls were subsequently injected IP with LPS (10 mg/kg;
      Escherichia coli). The remaining animals were injected with saline IP. Two hours
      later, all mice were injected IV with 50 MUCi of (18)F FDG. One hour later, the
      animals were euthanized, and biodistribution was measured. Tissues were weighed,
      and radioactivity was measured with a well-type gamma counter. Results were
      expressed as %dose/g tissue, mean +/- SEM. The combination of burn 7 days
      previously and LPS significantly increased mortality compared to animals with
      burn alone, LPS alone, or sham controls. Burn injury 7 days previously caused a
      significant decrease in (18)FDG uptake by the brain compared to sham controls.
      The combination of LPS and burn injury 7 days previously produced a significant
      increase in (18)FDG uptake by brown adipose tissue and heart compared with either
      treatment separately. LPS produced a significant increase in (18)FDG uptake by
      lung, spleen, and gastrointestinal tract of the sham animals, changes that were
      different in mice burned 7 days previously and injected with LPS. The present
      results suggest that burn injury 7 days previously predisposes mice to
      alterations in (18)FDG uptake produced by LPS. These changes may relate, in part,
      to the increased lethality of LPS injection in previously burned mice.

PMID- 22961013
TI  - Neutral and charged gallium clusters: structures, physical properties and
      implications for the melting features.
AB  - We report the putative Global Minimum (GM) structures and electronic properties
      of Ga(N)(+), Ga(N) and Ga(N)(-) clusters with N = 13-37 atoms, obtained from
      first-principles density functional theory structural optimizations. The
      calculations include spin polarization and employ an exchange-correlation
      functional which accounts for van der Waals dispersion interactions (vdW-DFT). We
      find a wide diversity of structural motifs within the located GM, including
      decahedral, polyicosahedral, polytetrahedral and layered structures. The GM
      structures are also extremely sensitive to the number of electrons in the
      cluster, so that the structures of neutral and charged clusters differ for most
      sizes. The main magic numbers (clusters with an enhanced stability) are
      identified and interpreted in terms of electronic and geometric shell closings.
      The theoretical results are consistent with experimental abundance mass spectra
      of Ga(N)(+) and with photoelectron spectra of Ga(N)(-). The size dependence of
      the latent heats of melting, the shape of the heat capacity peaks, and the
      temperature dependence of the collision cross-sections, all measured for Ga(N)(+)
      clusters, are properly interpreted in terms of the calculated cohesive energies,
      spectra of configurational excitations, and cluster shapes, respectively. The
      transition from "non-melter" to "magic-melter" behaviour, experimentally observed
      between Ga(30)(+) and Ga(31)(+), is traced back to a strong geometry change.
      Finally, the higher-than-bulk melting temperatures of gallium clusters are
      correlated with a more typically metallic behaviour of the clusters as compared
      to the bulk, contrary to previous theoretical claims.

PMID- 22961015
TI  - A significant step forward: new definitions for surveillance of infections in
      long-term care.

PMID- 22961014
TI  - Surveillance definitions of infections in long-term care facilities: revisiting
      the McGeer criteria.
AB  - (See the commentary by Moro, on pages  978-980 .)  Infection surveillance
      definitions for long-term care facilities (ie, the McGeer Criteria) have not been
      updated since 1991. An expert consensus panel modified these definitions on the
      basis of a structured review of the literature. Significant changes were made to
      the criteria defining urinary tract and respiratory tract infections. New
      definitions were added for norovirus gastroenteritis and Clostridum difficile
      infections.

PMID- 22961016
TI  - The use of live attenuated influenza vaccine (LAIV) in healthcare personnel
      (HCP): guidance from the Society for Healthcare Epidemiology of America (SHEA).
AB  - Because of the live viral backbone of live attenuated influenza vaccine (LAIV),
      questions have arisen regarding infection control precautions and restrictions
      surrounding its use in healthcare personnel (HCP). This document provides
      guidance from the Society for Healthcare Epidemiology of America regarding use of
      LAIV in HCP and the infection control precautions that are recommended with its
      use in this population.

PMID- 22961017
TI  - Outbreak of carbapenem-resistant enterobacteriaceae at a long-term acute care
      hospital: sustained reductions in transmission through active surveillance and
      targeted interventions.
AB  - OBJECTIVE: To describe a Klebsiella pneumoniae carbapenemase (KPC)-producing
      carbapenem-resistant Enterobacteriaceae (CRE) outbreak and interventions to
      prevent transmission. DESIGN, SETTING, AND PATIENTS: Epidemiologic investigation
      of a CRE outbreak among patients at a long-term acute care hospital (LTACH).
      METHODS: Microbiology records at LTACH A from March 2009 through February 2011
      were reviewed to identify CRE transmission cases and cases admitted with CRE. CRE
      bacteremia episodes were identified during March 2009-July 2011. Biweekly CRE
      prevalence surveys were conducted during July 2010-July 2011, and interventions
      to prevent transmission were implemented, including education and auditing of
      staff and isolation and cohorting of CRE patients with dedicated nursing staff
      and shared medical equipment. Trends were evaluated using weighted linear or
      Poisson regression. CRE transmission cases were included in a case-control study
      to evaluate risk factors for acquisition. A real-time polymerase chain reaction
      assay was used to detect the bla(KPC) gene, and pulsed-field gel electrophoresis
      was performed to assess the genetic relatedness of isolates. RESULTS: Ninety-nine
      CRE transmission cases, 16 admission cases (from 7 acute care hospitals), and 29
      CRE bacteremia episodes were identified. Significant reductions were observed in
      CRE prevalence (49% vs. 8%), percentage of patients screened with newly detected
      CRE (44% vs. 0%), and CRE bacteremia episodes (2.5 vs. 0.0 per 1,000 patient
      days). Cases were more likely to have received beta-lactams, have diabetes, and
      require mechanical ventilation. All tested isolates were KPC-producing K.
      pneumoniae, and nearly all isolates were genetically related. CONCLUSION: CRE
      transmission can be reduced in LTACHs through surveillance testing and targeted
      interventions. Sustainable reductions within and across healthcare facilities may
      require a regional public health approach.

PMID- 22961018
TI  - Device-associated infection rates, device utilization, and antimicrobial
      resistance in long-term acute care hospitals reporting to the National Healthcare
      Safety Network, 2010.
AB  - OBJECTIVE: To evaluate national data on healthcare-associated infections (HAIs),
      device utilization, and antimicrobial resistance in long-term acute care
      hospitals (LTACHs). DESIGN AND SETTING: Comparison of data from LTACHs and from
      medical and medical-surgical intensive care units (ICUs) in short-stay acute care
      hospitals reporting to the National Healthcare Safety Network (NHSN) during 2010.
      METHODS: Rates of central line-associated bloodstream infections (CLABSIs),
      catheter-associated urinary tract infections (CAUTIs), and ventilator-associated
      pneumonia (VAP) as well as device utilization ratios were calculated. For each
      HAI, pathogen profiles and antimicrobial resistance prevalence were evaluated.
      Comparisons were made using Poisson regression and the mood median and chi2
      tests. RESULTS: In 2010, 104 LTACHs reported CLABSIs and 57 reported CAUTIs and
      VAP to the NHSN. Median CLABSI rates in LTACHs (1.25 events per 1,000 device-days
      reported; range, 0.0-5.96) were comparable to rates in major teaching ICUs and
      were higher than those in other ICUs. CAUTI rates in LTACHs (median, 2.61; range,
      0.0-9.92) were higher and VAP rates (median, 0.0; range, 0.0-3.29) were generally
      lower than those in ICUs. Central line utilization in LTACHs was higher than that
      in ICUs, whereas urinary catheter and ventilator utilization was lower.
      Methicillin resistance among Staphylococcus aureus CLABSIs (83%) and vancomycin
      resistance among Enterococcus faecalis CAUTIs (44%) were higher in LTACHs than in
      ICUs. Multidrug resistance among Pseudomonas aeruginosa CAUTIs (25%) was higher
      in LTACHs than in most ICUs. CONCLUSIONS: CLABSIs and CAUTIs associated with
      multidrug-resistant organisms present a challenge in LTACHs. Continued HAI
      surveillance with pathogen-level data can guide prevention efforts in LTACHs.

PMID- 22961019
TI  - Predictors of hospital-acquired urinary tract-related bloodstream infection.
AB  - OBJECTIVE: Bloodstream infection (BSI) secondary to nosocomial urinary tract
      infection is associated with substantial morbidity, mortality, and additional
      financial costs. Our objective was to identify predictors of nosocomial urinary
      tract-related BSI. DESIGN: Matched case-control study. SETTING: Midwestern
      tertiary care hospital. PATIENTS: Cases (n=298) were patients with a positive
      urine culture obtained more than 48 hours after admission and a blood culture
      obtained within 14 days of the urine culture that grew the same organism.
      Controls (n=667), selected by incidence density sampling, included patients with
      a positive urine culture who were at risk for BSI but did not develop one.
      Methods. Conditional logistic regression and classification and regression tree
      analyses. RESULTS: The most frequently isolated microorganisms that spread from
      the urinary tract to the bloodstream were Enterococcus species. Independent risk
      factors included neutropenia (odds ratio [OR], 10.99; 95% confidence interval
      [CI], 5.78-20.88), renal disease (OR, 2.96; 95% CI, 1.98-4.41), and male sex (OR,
      2.18; 95% CI, 1.52-3.12). The probability of developing a urinary tract-related
      BSI among neutropenic patients was 70%. Receipt of immunosuppressants (OR, 1.53;
      95% CI, 1.04-2.25), insulin (OR, 4.82; 95% CI, 2.52-9.21), and antibacterials
      (OR, 0.66; 95% CI, 0.44-0.97) also significantly altered risk. CONCLUSIONS: The
      heightened risk of urinary tract-related BSI associated with several comorbid
      conditions suggests that the management of nosocomial bacteriuria may benefit
      from tailoring to certain patient subgroups. Consideration of time-dependent risk
      factors, such as medications, may also help guide clinical decisions in reducing
      BSI.

PMID- 22961020
TI  - Personal protective equipment management and policies: European Network for
      Highly Infectious Diseases data from 48 isolation facilities in 16 European
      countries.
AB  - OBJECTIVE: To collect data about personal protective equipment (PPE) management
      and to provide indications for improving PPE policies in Europe. DESIGN:
      Descriptive, cross-sectional survey. SETTING AND PARTICIPANTS: Data were
      collected in 48 isolation facilities in 16 European countries nominated by
      National Health Authorities for the management of highly infectious diseases
      (HIDs). METHODS: Data were collected through standardized checklists at on-site
      visits during February-November 2009. Indications for adequate PPE policies were
      developed on the basis of a literature review, partners' expert opinions, and the
      collected data. RESULTS: All facilities have procedures for the selection of PPE
      in case of HID, and 44 have procedures for the removal of PPE. In 40 facilities,
      different levels of PPE are used according to a risk assessment process, and in 8
      facilities, high-level PPE (e.g., positive-pressure complete suits or Trexler
      units) is always used. A fit test is performed at 25 of the 40 facilities at
      which it is applicable, a seal check is recommended at 25, and both procedures
      are used at 17. Strategies for promoting and monitoring the correct use of PPE
      are available at 42 facilities. In case of a sudden increase in demand, 44
      facilities have procedures for rapid supply of PPE, whereas 14 facilities have
      procedures for decontamination and reuse of some PPE. CONCLUSIONS: Most isolation
      facilities devote an acceptable level of attention to PPE selection and removal,
      strategies for the promotion of the correct use of PPE, and ensuring adequate
      supplies of PPE. Fit test and seal check procedures are still not widely
      practiced. Moreover, policies vary widely between and within European countries,
      and the development of common practice procedures is advisable.

PMID- 22961021
TI  - Registration of blood exposure accidents in The Netherlands by a nationally
      operating call center.
AB  - OBJECTIVE: Healthcare providers and other employees, especially those who do not
      work in a hospital, may not easily find help after the occurrence of a blood
      exposure accident. In 2006, a national call center was established in The
      Netherlands to fill this gap. METHODS: All occupational blood exposure accidents
      reported to the 24-hours-per-day, 7-days-per-week call center from 2007, 2008,
      and 2009 were analyzed retrospectively for incidence rates, risk assessment,
      handling, and preventive measures taken. RESULTS: A total of 2,927 accidents were
      reported. The highest incidence rates were reported for private clinics and
      hospitals (68.5 and 54.3 accidents per 1,000 person-years, respectively). Dental
      practices started reporting incidents frequently after the arrangement of a
      collective financial agreement with the call center. Employees of ambulance
      services, midwife practices, and private clinics reported mostly high-risk
      accidents, whereas penitentiaries frequently reported low-risk accidents.
      Employees in mental healthcare facilities, private clinics, and midwife practices
      reported accidents relatively late. The extent of hepatitis B vaccination in
      mental healthcare facilities, penitentiaries, occupational health services, and
      cleaning services was low (<70%). CONCLUSION: The national call center
      successfully organized the national registration and handling of blood exposure
      accidents. The risk of blood exposure accidents could be estimated on the basis
      of this information for several occupational branches. Targeted preventive
      measures for healthcare providers and other employees at risk can next be
      developed.

PMID- 22961022
TI  - Active surveillance and decolonization of methicillin-resistant Staphylococcus
      aureus on admission to neonatal intensive care units in Hong Kong: a cost
      effectiveness analysis.
AB  - OBJECTIVE: To examine potential clinical outcomes and cost of active methicillin
      resistant Staphylococcus aureus (MRSA) surveillance with and without
      decolonization in neonatal intensive care units (NICUs) from the perspective of
      healthcare providers in Hong Kong. DESIGN: Decision analysis modeling. SETTING:
      NICU. PATIENTS: Hypothetical cohort of patients admitted to an NICU. METHODS: We
      designed a decision tree to simulate potential outcomes of active MRSA
      surveillance with and without decolonization in patients admitted to an NICU.
      Outcome measures included total direct medical cost per patient, MRSA infection
      rate, and MRSA-associated mortality rate. Model inputs were derived from the
      literature. Sensitivity analyses evaluated the impact of uncertainty in all model
      variables. RESULTS: In the base-case analysis, active surveillance plus
      decolonization showed a lower expected MRSA infection rate (0.911% vs. 1.759%),
      MRSA-associated mortality rate (0.223% vs. 0.431%), and total cost per patient
      (USD 47,294 vs. USD 48,031) compared with active surveillance alone. Sensitivity
      analyses showed that active surveillance plus decolonization cost less and had
      lower event rates if the incidence risk ratio of acquiring MRSA infections in
      carriers after decolonization was less than 0.997. In 10,000 Monte Carlo
      simulations, active surveillance plus decolonization was significantly less
      costly than active surveillance alone 99.9% of the time, and both the MRSA
      infection rate and the MRSA-associated mortality rate were significantly lower
      99.9% of the time. CONCLUSIONS: Active surveillance plus decolonization for
      patients admitted to NICUs appears to be cost saving and effective in reducing
      the MRSA infection rate and the MRSA-associated mortality rate if addition of
      decolonization to active surveillance reduces the risk of MRSA infection.

PMID- 22961023
TI  - Epidemiology and healthcare costs of incident Clostridium difficile infections
      identified in the outpatient healthcare setting.
AB  - OBJECTIVE: To describe the epidemiology and healthcare costs of Clostridium
      difficile infection (CDI) identified in the outpatient setting. DESIGN:
      Population-based, retrospective cohort study. PATIENTS: Kaiser Permanente
      Colorado and Kaiser Permanente Northwest members between June 1, 2005, and
      September 30, 2008. METHODS: We identified persons with incident CDI and
      classified CDI by whether it was identified in the outpatient or inpatient
      healthcare setting. We collected information about baseline variables and follow
      up healthcare utilization, costs, and outcomes among patients with CDI. We
      compared characteristics of patients with CDI identified in the outpatient versus
      inpatient setting. RESULTS: We identified 3,067 incident CDIs; 56% were
      identified in the outpatient setting. Few strong, independent predictors of
      diagnostic setting were identified, although a previous stay in a nonacute
      healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13
      1.86]) was statistically associated with outpatient-identified CDI, as was age
      from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95%
      CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared
      with persons aged 80-89 years. CONCLUSIONS: We found that more than one-half of
      incident CDIs in this population were identified in the outpatient setting.
      Patients with outpatient-identified CDI were younger with fewer comorbidities,
      although they frequently had previous exposure to healthcare. These data suggest
      that practitioners should be aware of CDI and obtain appropriate diagnostic
      testing on outpatients with CDI symptoms.

PMID- 22961024
TI  - Daily disinfection of high-touch surfaces in isolation rooms to reduce
      contamination of healthcare workers' hands.
AB  - In a randomized nonblinded trial, we demonstrated that daily disinfection of high
      touch surfaces in rooms of patients with Clostridium difficile infection and
      methicillin-resistant Staphylococcus aureus colonization reduced acquisition of
      the pathogens on hands after contacting high-touch surfaces and reduced
      contamination of hands of healthcare workers caring for the patients.

PMID- 22961025
TI  - Laboratory-confirmed pandemic h1n1 influenza in hospitalized adults: findings
      from the Canadian Nosocomial Infections Surveillance Program, 2009-2010.
AB  - Surveillance for pandemic H1N1 influenza was conducted between June 1, 2009, and
      May 31, 2010, among adults at 40 participating hospitals in the Canadian
      Nosocomial Infection Surveillance Program. The first wave was characterized by a
      higher proportion of Aboriginals and pregnant women as well as severe outcomes,
      compared to the second wave.

PMID- 22961026
TI  - An outbreak of scabies in multiple linked healthcare settings in The Netherlands.
AB  - We report a large scabies outbreak occurring in Tilburg, Netherlands, which
      affected several different healthcare settings that provide care to the elderly
      and the mentally disabled. The outbreak demonstrated how the complex system of
      care provision to vulnerable groups facilitated extensive scabies transmission
      among multiple linked healthcare settings and the community.

PMID- 22961027
TI  - Lack of seasonality in the occurrence of multidrug-resistant Acinectobacter
      baumannii complex.

PMID- 22961028
TI  - Epidemiology and clinical features of community-onset Acinetobacter baumannii
      infections.

PMID- 22961029
TI  - Variation in the use of diagnostic bronchoscopy among intensive care unit
      patients: implications for surveillance.

PMID- 22961030
TI  - Preventing catheter-associated urinary tract infections: hospital location of
      catheter insertion.

PMID- 22961031
TI  - Review of evidence for alcohol-based skin preparation agents.

PMID- 22961032
TI  - Chlorhexidine does not select for resistance in Staphylococcus aureus isolates in
      a community setting.

PMID- 22961033
TI  - Retrospective analysis of culture-positive peripherally inserted central catheter
      infections at an academic medical center.

PMID- 22961034
TI  - Surveillance for influenza using hospital discharge data may underestimate the
      burden of influenza-related hospitalization.

PMID- 22961035
TI  - An analysis of the accuracy of physician-entered indications on computerized
      antimicrobial orders.

PMID- 22961036
TI  - Cyclic AMP and cyclic AMP-receptor protein modulate the autoinducer-2-mediated
      quorum sensing system in Vibrio vulnificus.
AB  - This study was undertaken to determine whether cyclic AMP (cAMP) or cAMP-receptor
      protein (CRP) modulates the activity of the autoinducer (AI)-2-mediated quorum
      sensing (QS) system in response to glucose availability in Vibrio vulnificus. A
      mutation in crp impaired V. vulnificus growth, decreased AI-2 production, and
      repressed the expression of smcR encoding the master regulator SmcR (a Vibrio
      harveyi LuxR homolog) of the AI-2-QS system, and these changes were prevented by
      in trans complementation of wild-type crp. Furthermore, glucose repressed smcR
      expression in the presence of CRP but not in its absence. A mutation in cyaA
      encoding adenylate cyclase, which is required for cAMP synthesis, also impaired
      V. vulnificus growth and repressed smcR expression, and these changes were
      recovered by in trans complementation of wild-type cyaA. These results indicate
      that cAMP or CRP modulates the AI-2-QS system in response to glucose availability
      in V. vulnificus, demonstrating the presence of a connection between catabolite
      repression and quorum sensing in V. vulnificus.

PMID- 22961038
TI  - Hemoglobin point-of-care testing: the HemoCue system.
AB  - Besides the use of traditional laboratory resources, the diagnosis of anemia can
      also be accomplished by assessing hemoglobin (Hb) concentration with point-of
      care testing (POCT) devices such as the HemoCue test systems. In several
      situations, these devices might suitably replace traditional laboratory testing,
      including several areas of health care where a very rapid Hb measurement might be
      required to make immediate therapeutic decisions. The use of these devices,
      however, should fulfill some basic criteria, including economic, clinical, and
      regulatory issues; appropriate training of the users and knowledge of test
      requirements, performance, limitations, and potential interferences; the use of
      venous and arterial sampling, when possible; and a rigorous quality assessment,
      which should be under the responsibility of laboratory professionals. Because of
      its optimal performance along with the fact that the HemoCue is probably one of
      the most commonly used devices worldwide, the aim of this article is to review
      the literature data about the performance of this test system as compared with
      laboratory reference testing estimations and according to the biological matrix.

PMID- 22961037
TI  - Survey of heritable endosymbionts in southern Mexico populations of the fruit fly
      species Anastrepha striata and A. ludens.
AB  - Heritable endosymbiotic bacteria associated with insects are ubiquitous and
      taxonomically diverse. Many of these endosymbionts influence the fitness of their
      hosts and/or manipulate their host reproduction. Exploiting the effects of
      endosymbionts on hosts for pest control is a growing research area, but requires
      knowledge of endosymbionts associated with the target pest population. In this
      study, we used molecular methods to screen southern Mexico populations of two
      species of tephritid fruit fly pests, Anastrepha ludens and A. striata, for
      heritable bacteria. The only heritable endosymbiont found was Wolbachia in A.
      striata. Based on multilocus sequence typing and phylogenetic analyses, this
      Wolbachia strain is new and belongs to the Wolbachia supergroup B. Wolbachia
      strains previously reported in members of the genus Anastrepha in South America
      belong to supergroup A. We discuss the potential implications for pest control of
      the presence of a different Wolbachia strain in southern Mexico.

PMID- 22961039
TI  - [The diagnostic risk of overlooking temporal arteritis].
AB  - We report two cases of atypical temporal arteritis. A 73-year-old woman with
      typical internal (diabetes, hypertony, hypercholesterinemia) and ophthomological
      (optic disc drusen) risk factors for N-AION reported with an acute unilateral
      decrease in vision. General symptoms, laboratory analysis and biopsy led to the
      diagnosis of temporal arteritis and iv steroids were administered. An 83-year-old
      male patient reported with a sudden unilateral decrease in vision, but did not
      complain about general symptoms. Laboratory analysis revealed no signs for
      temporal arteritis, therefore the patient was referred to his internal specialist
      for evaluation of internal risk factors for N-AION. A few days later the patient
      reported with a unilateral decrease in vision of the partner eye. This time blood
      analysis was suggestive of temporal arteritis although no general symptoms were
      reported. Diagnosis was supported by a biopsy of the temporal artery and steroids
      were administered. These two cases teach us how dangerously easy temporal
      arteritis can be overlooked and that we have to take even the slightest hint for
      temporal arteritis seriously and initiate treatment as early as possible.

PMID- 22961040
TI  - [Management of childhood glaucoma associated with Sturge-Weber syndrome].
AB  - PURPOSE: Sturge-Weber syndrome is a rare congenital disorder consisting of
      cutaneous, leptomeningeal and ocular vascular malformations. Glaucoma occurs in
      30-70 % of patients. Treatment is challenging due to a high risk of severe
      complications such as expulsive haemorrhage, massive choroidal effusion and
      serous retinal detachment. Ocular findings and the occurrence of complications
      under different treatment modalities have been reviewed. METHODS: A retrospective
      analysis of a case series of 5 children (5 eyes/mean age 5.6 years) with
      secondary glaucoma associated with Sturge-Weber syndrome was undertaken. Ocular
      findings, treatment modalities, intraocular pressure and complications were
      assessed. RESULTS: Facial port-wine nevus, i.e., nevus flammeus and dilated
      episcleral vessels were present in all cases. Diffuse choroidal haemangiomas were
      seen in four eyes. Glaucoma surgery was performed in 4 children, one child was
      treated with antiglaucomatous medication alone. Reversible uveal effusion and
      subluxation of the lens appeared postoperatively in one eye, persistent serous
      retinal detachment occurred 3 years after surgery in another eye (with an
      intraocular pressure of 10 mmHg). Both complications were found in eyes with
      diffuse choroidal haemangioma. CONCLUSION: Management of glaucoma associated with
      Sturge-Weber syndrome is difficult and controversial. Medical treatment often
      does not decrease intraocular pressure sufficiently. When planning surgical
      intervention an increased risk of severe complications has to be considered,
      especially in the presence of diffuse choroidal haemangioma.

PMID- 22961041
TI  - [Trabeculectomy versus canaloplasty--utility and cost-effectiveness analysis].
AB  - PURPOSE: Due to increasing cost pressure in the public health system treatments
      and their costs are highly relevant in the therapy for chronic diseases such as
      glaucoma. In the era of diagnosis-related group (DRG) reimbursement, new
      interventions need to prove not only their safety and effectiveness but also
      their cost-utility. Canaloplasty as a new interventional surgery is compared to
      trabeculectomy (TE) by means of a cost and effort analysis. METHODS: In this
      retrospective, consecutive case series patients were compared as follows: group
      I, 21 eyes of 21 patients undergoing canaloplasty from 2009 on and group II, 48
      eyes of 42 patients, who were treated with TE with mitomycin C (MMC) from 2001 to
      2004 and had intensified postoperative care. Data regarding demography, duration
      of hospitalisation, duration of surgery, surgical complications and
      interventions, and pre- and post-operative IOP were analysed within the first 6
      months post operation. RESULTS: In group I mean duration of hospitalisation was
      5.3 +/- 0.8 days (d) and in group II 10.7 +/- 2.8 d. Duration of surgery was 77
      +/- 14 min in group I and in group II 48 +/- 11 min. On average 2.8 +/- 1.0
      visits were needed during follow-up in group I and 6 +/- 1.5 visits in group II.
      The mean preoperative IOP of 28.75 +/- 9.6 mmHg was lowered to 12.8 +/- 3.3 mmHg
      after six months in group I and in group II from 34.5 +/- 13.4 mmHg to 10.3 +/-
      4.5 mmHg. In group I, a total of 4 interventions were seen within the first six
      months without re-admission. In group II 107 interventions and eleven re
      admissions were necessary. Mean costs for hospitalisation amount to 821.50 ? in
      group I and 1658.50 ? in group II. Overall expenses were 2379.62 ? for
      canaloplasty and 2733.61 ? for TE. CONCLUSION: Both interventions could
      effectively control IOP. However, trabeculectomy requires a longer
      hospitalisation, has higher re-admission rates and needs more frequent
      postoperative controls, which makes TE more costly and time-consuming than
      canaloplasty.

PMID- 22961042
TI  - [Study on the time course of macular pigment density measurement in patients with
      a macular hole--clinical course and impact of surgery].
AB  - BACKGROUND: In a prospective clinical study we examined the course of the optical
      density of the macular pigment (MPOD) in patients with idiopathic macular holes
      before and after pars-plana vitrectomy. PATIENTS AND METHODS: Of the 26 patients
      four had macular holes stage 1, six patients had stage 2 or stage 4 holes and ten
      people had a macular hole stage 3. The surgical procedure consisted always of a
      standard 3-port pars plana vitrectomy (PPV) with colouring assisted peeling of
      the internal limiting membrane. The optical density of macular pigment was
      determined by the 1-wavelength reflection method before pars plana vitrectomy and
      after macular hole closure. RESULTS: The macular hole was completely closed in 25
      of 26 eyes (96.15 %). This anatomical success is also the basis for a
      postoperative improvement in the retinal function. In the case of macular holes
      from stages 3 and 4 the surgery achieved an increase in visual acuity and an
      increase of the optical density of the the macular pigment. In patients with
      macular holes stage 2 the visual acuity and the optical density of the macular
      pigment were reduced after vitrectomy. In the case of stage 1 holes the visual
      acuity and the volume of macular pigment also were reduced after the operation.
      DISCUSSION: In the group of stage 4 macular holes there was a significant
      increase in maximum optical density and volume of macular pigment after
      successful surgical hole closure, so the functional profit of PPV is very high in
      these patients. Even in the case of macular holes of stage 3 the PPV effected a
      functional improvement in the sense of an increase of the optical density of
      macular pigment. The increase in volume proved to be significant. For macular
      holes stage 2 the vitrectomy as a therapy option is generally recognised but PPV
      does not effect positively the height of the optical density of macular pigment.
      In these patients both the maximum optical density as well as the volume of
      macular pigment were reduced in the therapeutic course. Whether surgical
      intervention is indicated in stage 1 is still controversial. Taking into account
      the development of MPOD the profit from surgery for the patients is very low.
      This led to a decrease in volume of macular pigment and only a slight increase in
      maximum optical density after pars plana vitrectomy.

PMID- 22961043
TI  - [Retinopathy of prematurity - pathophysiologic mechanisms and new treatment
      options].
AB  - Retinopathy of prematurity (ROP), like other angioproliferative retinal
      disorders, has witnessed the advent of anti-VEGF therapy in clinical practice.
      The first report from the BEAT-ROP study published in 2011 represents the first
      comparison of anti-VEGF therapy versus conventional laser treatment in a
      randomised controlled trial. This review article investigates these novel aspects
      of ROP therapy from a pathophysiological angle and delineates the stages of ROP
      in which anti-VEGF treatment appears as a reasonable option. Furthermore, the
      novel chances of anti-VEGF therapy are being weighed against some still
      unanswered questions and novel study concepts are being presented.

PMID- 22961044
TI  - Characterization of two mammalian cortical collecting duct cell lines with
      hopping probe ion conductance microscopy.
AB  - We morphologically and physiologically characterized Madin-Darby canine kidney
      (MDCK) cell and mouse principal cell of kidney in cortical collecting duct
      (mpkCCD) via hopping probe ion conductance microscopy, transepithelial electrical
      resistance (TEER) measurements, and single-channel recordings. The specific
      membrane structures of microvilli and tight junctions were clearly observed in
      MDCK and mpkCCD cell monolayers. The electrophysiological functions of epithelial
      Na(+) channel in MDCK and mpkCCD cells were further characterized by measuring
      amiloride-sensitive TEER values for the whole-cell monolayer and detecting the
      ion channel activities with patch clamping. Our results provide more
      morphological and functional information to help better utilize these two
      mammalian CCD cell lines for mechanism studies of sodium absorption and
      reabsorption in the distal nephron.

PMID- 22961045
TI  - Prediction of lipid-binding regions in cytoplasmic and extracellular loops of
      membrane proteins as exemplified by protein translocation membrane proteins.
AB  - The presence of possible lipid-binding regions in the cytoplasmic or
      extracellular loops of membrane proteins with an emphasis on protein
      translocation membrane proteins was investigated in this study using
      bioinformatics. Recent developments in approaches recognizing lipid-binding
      regions in proteins were found to be promising. In this study a total
      bioinformatics approach specialized in identifying lipid-binding helical regions
      in proteins was explored. Two features of the protein translocation membrane
      proteins, the position of the transmembrane regions and the identification of
      additional lipid-binding regions, were analyzed. A number of well-studied protein
      translocation membrane protein structures were checked in order to demonstrate
      the predictive value of the bioinformatics approach. Furthermore, the results
      demonstrated that lipid-binding regions in the cytoplasmic and extracellular
      loops in protein translocation membrane proteins can be predicted, and it is
      proposed that the interaction of these regions with phospholipids is important
      for proper functioning during protein translocation.

PMID- 22961046
TI  - High symptom improvement and local tumor control using stereotactic radiotherapy
      when given early after diagnosis of meningioma. A multicentre study.
AB  - PURPOSE: The goal of the present study was to analyze long-term results of
      fractionated stereotactic radiotherapy (SRT) in patients with a meningioma.
      METHODS AND MATERIALS: A total of 72 patients treated between 1996 and 2008 in
      MAASTRO clinic (n = 45) and University Hospital Zurich (n = 27) were included.
      SRT was given as primary treatment (n = 46), postoperatively (n = 19) or at
      recurrence (n = 7); 49 tumours (68%) were located in the skull base. Median total
      dose was 54 Gy. RESULTS: Median follow-up was 4.13 years (range 0.66-11 years).
      The 3- and 5-year overall survival were 92 and 79% for grade 0 and I meningioma.
      Progression-free survival for grade 0 and I was 95% at 3 and 5 years, and 40% for
      grade II and III at 3 years. In 98.4% of patients, clinical symptoms were stable
      or improved. The majority of symptoms improved within 24 months after SRT. Local
      control is significantly better if patients are irradiated immediately after
      diagnosis compared to a watchful waiting policy (p = 0.017). Grade IV toxicity
      was low (4.2%, n = 3) CONCLUSION: SRT is an effective treatment with high local
      and clinical control. Early SRT resulted in better outcome than late treatment at
      progression.

PMID- 22961047
TI  - Home care use of intravenous and subcutaneous immunoglobulin for primary
      immunodeficiency in the United States.
AB  - PURPOSE: Utilization reports on immunoglobulin (Ig) use for immunodeficiency in
      the United States (U.S.) have focused on prescribing practices in hospitals.
      There have been no large-scale reports on Ig use for immune deficiency in the
      home. We investigated the use of Ig in 3,187 subjects diagnosed with primary
      immunodeficiency. METHODS: Cross-sectional data on 4,580 subjects in the U.S.
      receiving Ig in 2011 was obtained from a major home care provider. Demographics,
      route, dose, and frequency of Ig use by subjects with ICD-9 coded primary
      immunodeficiencies were analyzed. RESULTS: Of 4,580 subjects, 3,187 had ICD-9
      codes suggesting primary immunodeficiencies; 1,939 (60.8 %) were females and
      1,248 (39.2 %) were males, with age ranging from 0 to 95 years. The predominant
      diagnoses were: common variable immunodeficiency (279.06; n=1,764; 55.3 %),
      hypogammaglobulinemia (279.00; n=635; 19.9 %), unspecified immunity deficiency
      (279.3; n=286; 9 %), other selective Ig deficiencies (279.03; n=171; 5.4 %), and
      agammaglobulinemia (279.04; n=127; 4 %). 54 % of subjects received Ig by the
      subcutaneous (SC) route, and 46 % by intravenous (IV) route, with more SC use by
      older subjects. The mean dose prescribed was 483 mg/kg/month, but less Ig was
      ordered for subjects on SCIg (409 mg/kg/month), as compared to subjects on IVIg
      (568 mg/kg/month). A highly significant inverse correlation between increasing
      age and dosage of Ig ordered was found (P= <.0001). CONCLUSION: Analysis of home
      care use of Ig in primary immune deficiency revealed that the SC route was
      prescribed more than the IV route, especially for older patients. By either
      method of administration, less immunoglobulin was prescribed for older subjects.

PMID- 22961048
TI  - Selective expansion of pro-inflammatory chemokine CCL2-loaded CD14+CD16+
      monocytes subset in HIV-infected therapy naive individuals.
AB  - We have previously demonstrated the critical role of C-C chemokine CCL2 in HIV-1
      pathogenesis, and circulating monocytes as the major source of CCL2. Since the
      functional aspect of monocyte subsets in context to CCL2 production is unclear,
      we investigated the frequency and production of CCL2 by circulating monocyte
      subsets in a cohort of HIV- therapy naive patients. A cohort of HIV-infected
      therapy naive patients (n=9) and healthy controls (n=6) were recruited for this
      study. To examine monocyte subset frequency and CCL2 production, we performed
      surface and intra-cellular staining of freshly isolated peripheral blood
      mononuclear cells (PBMC) and subjected to flow cytometry. A preferential
      expansion of CD14(+)CD16(+) monocyte subset, coupled with increased intracellular
      production of CCL2 was observed in HIV-1 patients compared to healthy controls.
      Interestingly this phenotype was mostly restricted to CD14(+)CD16(+) monocyte
      subsets. This study identifies pro-inflammatory CCL2 producing CD14(+)CD16(+)
      monocyte subset that expands selectively in HIV-1 infection and could potentially
      participate in causing immuno-pathology.

PMID- 22961049
TI  - [Curricula oriented inclusion of children and adolescents with haemophilia in
      school sports--a new approach within the project "fit for life"].
AB  - Inclusive paedagogic thinking and acting is a modern and increasingly important
      topic in school sports. It will affect teachers as well as parents and students.
      The new international guidelines and national curricula enable new ways of
      inclusion especially for students with chronic illnesses like haemophilia.
      Special help from the sport teachers is of vital importance.  In our project "fit
      for life" where we advice children and young adults with haemophilia to find
      their appropriate sport, we developed a new approach for an optimised inclusion
      of children with haemophilia into sport lessons. The whole project is running in
      corporation with the German Sport Teachers Association/Hessen. We analysed and
      rated the actual curricula of the different school years and looked at the
      specific needs, risks and necessary abilities for persons with haemophilia. By
      this means we gathered about 600 typical movements and/or exercises for school
      sports and developed individual advice and adapted exercise solutions for sport
      lessons.

PMID- 22961050
TI  - Inhibition of mouse urinary bladder carcinogenesis by acai fruit (Euterpe
      oleraceae Martius) intake.
AB  - Acai, fruit from Euterpe oleraceae Martius, is consumed in natura and in a
      variety of beverages and food preparations and possesses several potential
      antioxidant compounds. In a first study for anticarcinogenicity screening, male
      Swiss mice (n = 20/per group) were chemically-induced to urothelial bladder
      carcinogenesis for 10 weeks and received a standard diet or a standard diet
      containing 2.5 and 5 % spray-dried acai pulp (AP) for 10 weeks. At week 20, the
      incidence of simple and nodular hyperplasia and the incidence and multiplicity of
      transitional cell carcinoma (TCC) were evaluated. In a second study for
      antigenotoxicity screening, male Swiss mice (n = 6/per group) were fed standard
      diet or standard diet containing 5 % AP for three weeks. Urothelial cell
      suspensions were obtained and challenged with H(2)O(2) for induction of DNA
      damage and analyzed by comet assay. Overall, dietary 5 % AP reduced TCC incidence
      and multiplicity (p = 0.019 and p = 0.015, respectively) and tumor cell
      proliferation and p63 expression (p = 0.02 and p = 0.007, respectively),
      Furthermore, the group fed the 5 % AP presented a significant reduction (p <
      0.01) in DNA damage induced by H(2)O(2), a notable oxidant agent. The results
      suggest that the spray-dried acai pulp used here inhibits the TCC development in
      male Swiss mice, probably due to its potential antioxidant action.

PMID- 22961051
TI  - Treatment updates in advanced thymoma and thymic carcinoma.
AB  - OPINION STATEMENT: Thymomas and thymic carcinomas are rare diseases of the
      anterior mediastinum. Although some thymomas are quite indolent and able to be
      resected in a curative fashion, the treatment of metastatic disease remains a
      challenge, especially for the more aggressive thymic carcinoma histology. Based
      on the results of single-arm trials, combination chemotherapy is the standard of
      care in the first-line, and anthracycline-based treatments should be used if
      patients are reasonably fit. Several single-agent cytotoxic chemotherapy agents
      have some effectiveness in subsequent lines of therapy, especially pemetrexed
      and, in octreotide scan-positive patients, octreotide. Prospective trials of new
      agents are difficult to conduct given the rarity of thymoma, but various targeted
      therapies do show promise. Greater international research collaboration, as well
      as modern techniques in molecular and genomic characterization, should help to
      advance the treatment of thymic malignancies in the near future.

PMID- 22961054
TI  - Alkaline earth metal complexes of a chiral polyether as initiator for the ring
      opening polymerization of lactide.
AB  - A chiral, tetradentate polyether ligand with a trans-1,2-cyclohexanediyl
      backbone, bis(methoxyethoxy)-trans-1,2-cyclohexane (5), was synthesized as both a
      racemate and the (S,S) enantiomer. 5 was found to form stable adducts with
      alkaline earth metal amides [M{N(SiMe(3))(2)}(2)(thf)(x)] (M = Mg (x = 0), Ca (x
      = 2) and Sr (x = 2/3)), [Ca{N(SiHMe(2))(2)}(2)(thf)] as well as with hydrocarbyl
      compounds [Mg(CH(2)SiMe(3))(2)] and [Ca(eta(3)-C(3)H(5))(2)]. X-ray diffraction
      study of the bis(amide) [((S,S)-)Ca{N(SiMe(3))(2)}(2)] and of the bis(allyl)
      [(rac-5)Ca(eta(3)-C(3)H(5))(2)] was performed. The complexes obtained were tested
      as initiators for the ring-opening polymerization of meso-, racemic and L
      lactide.

PMID- 22961052
TI  - Induction and molecular signature of pathogenic TH17 cells.
AB  - Interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are often present
      at the sites of tissue inflammation in autoimmune diseases, which has led to the
      conclusion that T(H)17 cells are main drivers of autoimmune tissue injury.
      However, not all T(H)17 cells are pathogenic; in fact, T(H)17 cells generated
      with transforming growth factor-beta1 (TGF-beta1) and IL-6 produce IL-17 but do
      not readily induce autoimmune disease without further exposure to IL-23. Here we
      found that the production of TGF-beta3 by developing T(H)17 cells was dependent
      on IL-23, which together with IL-6 induced very pathogenic T(H)17 cells.
      Moreover, TGF-beta3-induced T(H)17 cells were functionally and molecularly
      distinct from TGF-beta1-induced T(H)17 cells and had a molecular signature that
      defined pathogenic effector T(H)17 cells in autoimmune disease.

PMID- 22961053
TI  - A multiply redundant genetic switch 'locks in' the transcriptional signature of
      regulatory T cells.
AB  - The transcription factor Foxp3 participates dominantly in the specification and
      function of Foxp3(+)CD4(+) regulatory T cells (T(reg) cells) but is neither
      strictly necessary nor sufficient to determine the characteristic T(reg) cell
      signature. Here we used computational network inference and experimental testing
      to assess the contribution of other transcription factors to this. Enforced
      expression of Helios or Xbp1 elicited distinct signatures, but Eos, IRF4, Satb1,
      Lef1 and GATA-1 elicited exactly the same outcome, acting in synergy with Foxp3
      to activate expression of most of the T(reg) cell signature, including key
      transcription factors, and enhancing occupancy by Foxp3 at its genomic targets.
      Conversely, the T(reg) cell signature was robust after inactivation of any single
      cofactor. A redundant genetic switch thus 'locked in' the T(reg) cell phenotype,
      a model that would account for several aspects of T(reg) cell physiology,
      differentiation and stability.

PMID- 22961055
TI  - Calbindin-D9k as a sensitive molecular biomarker for evaluating the synergistic
      impact of estrogenic chemicals on GH3 rat pituitary cells.
AB  - Various endocrine-disrupting chemicals (EDCs) such as bisphenol A (BPA),
      alkylphenols [4-nonylphenol (NP) and 4-tert octylphenol (OP)] and isobutylparaben
      (IBP) are a constant concern due to their widespread distribution. It has been
      reported that some combinations of hormone-disrupting chemicals are much more
      powerful than any of the chemicals alone. In this study, we measured the
      expression of an estrogenic biomarker gene, calbindin-D9k (CaBP-9k), and
      progesterone receptor (PR) to evaluate the individual or combined estrogenic
      activity of BPA, NP, OP and IBP in GH3 rat pituitary cells. Most doses of the
      individual compounds and all the doses of the combined chemicals significantly
      increased CaBP-9k and PR mRNA and protein expression compared to the vehicle
      (except for PR expression after treatment with OP and NP at 10-7 M). Of note,
      high doses (10-6 and 10-5 M) of the EDC combinations increased the translational
      and transcriptional levels of CaBP-9k by 1.3- to 2.4-fold compared to each
      individual equivalent concentrations of EDCs. To determine whether the increased
      CaBP-9k gene expression was induced via intracellular estrogen receptor (ER), we
      blocked ER signaling using fulvestrant, an ER antagonist. The results showed that
      fulvestrant significantly reversed the CaBP-9k and PR upregulation following
      treatment with individual EDCs or their combinations. Taken together, we conclude
      that combinations of BPA, NP, OP and IBP in GH3 rat pituitary cells have
      synergistic estrogenic activities mediated by ER signaling. In addition, the
      expression of the CaBP-9k gene may be used as a biomarker to assess the
      synergistic effects of EDCs in vitro.

PMID- 22961056
TI  - Unusual ocular manifestations of dengue fever in a young girl.

PMID- 22961057
TI  - Bone recurrence after curative resection of gastric cancer.
AB  - BACKGROUND: Standard follow up for bone recurrence has not yet been established
      for gastric cancer after surgical resection. The aim of this study was to
      investigate the incidence of and related risk factors for bone recurrence after
      surgical resection of gastric cancer. METHODS: A cohort of 3035 gastric cancer
      patients after curative resection was reviewed. We analyzed the patients who had
      bone scintigraphy before the surgery as well as during the follow-up period. The
      incidence of and the risk factors for bone recurrence after surgical resection of
      gastric cancer were investigated. RESULTS: In a total of 1683 patients analyzed,
      bone recurrence was detected in 30 patients (1.8%). The incidence of bone
      recurrence was significantly higher in advanced gastric cancers than in early
      lesions (3.5 vs. 0.4%, p < 0.01). The most common recurrence site was the spine,
      followed by pelvic bone and rib. Most patients had multiple bone metastases. The
      median time for recurrence was 28 months (range 4-111) from the surgery. In
      univariate analysis, the recurrence rate was higher in the tumors with large
      size, undifferentiated pathology, location in the body, and advanced stage. In
      multivariate analysis, lymph node metastasis (N2/N3 vs. N0/N0I) was the most
      predictable risk factor for bone recurrence [hazard ratio [HR] 1.44 (95%
      confidence interval [CI] 1.217-1.694)] and depth of invasion (T2-4 vs. T1) was
      also independently associated with bone recurrence. CONCLUSIONS: The incidence of
      bone recurrence was low after curative surgery in patients with gastric cancer.
      Intensive follow up with bone scintigraphy seems to be unnecessary in these
      patients.

PMID- 22961058
TI  - Ontogenetic symmetry and asymmetry in energetics.
AB  - Body size (= biomass) is the dominant determinant of population dynamical
      processes such as giving birth or dying in almost all species, with often
      drastically different behaviour occurring in different parts of the growth
      trajectory, while the latter is largely determined by food availability at the
      different life stages. This leads to the question under what conditions
      unstructured population models, formulated in terms of total population biomass,
      still do a fair job. To contribute to answering this question we first analyze
      the conditions under which a size-structured model collapses to a dynamically
      equivalent unstructured one in terms of total biomass. The only biologically
      meaningful case where this occurs is when body size does not affect any of the
      population dynamic processes, this is the case if and only if the mass-specific
      ingestion rate, the mass-specific biomass production and the mortality rate of
      the individuals are independent of size, a condition to which we refer as
      "ontogenetic symmetry". Intriguingly, under ontogenetic symmetry the equilibrium
      biomass-body size spectrum is proportional to 1/size, a form that has been
      conjectured for marine size spectra and subsequently has been used as prior
      assumption in theoretical papers dealing with the latter. As a next step we
      consider an archetypical class of models in which reproduction takes over from
      growth upon reaching an adult body size, in order to determine how quickly
      discrepancies from ontogenetic symmetry lead to relevant novel population
      dynamical phenomena. The phenomena considered are biomass overcompensation, when
      additional imposed mortality leads, rather unexpectedly, to an increase in the
      equilibrium biomass of either the juveniles or the adults (a phenomenon with
      potentially big consequences for predators of the species), and the occurrence of
      two types of size-structure driven oscillations, juvenile-driven cycles with
      separated extended cohorts, and adult-driven cycles in which periodically a front
      of relatively steeply decreasing frequencies moves up the size distribution. A
      small discrepancy from symmetry can already lead to biomass overcompensation;
      size-structure driven cycles only occur for somewhat larger discrepancies.

PMID- 22961059
TI  - Stromal cells expressing hedgehog-interacting protein regulate the proliferation
      of myeloid neoplasms.
AB  - Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide
      variety of human cancers including cancer stem cells. However, involvement of the
      Hh-signaling system in the bone marrow (BM) microenvironment during the
      development of myeloid neoplasms is unknown. In this study, we assessed the
      expression of Hh-related genes in primary human CD34(+) cells, CD34(+) blastic
      cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer,
      smoothened (SMO), were expressed in CD34(+) acute myeloid leukemia (AML) and
      myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was
      relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh
      signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived
      stromal cells was markedly lower than in healthy donor-derived stromal cells.
      Moreover, HHIP expression levels in BM stromal cells highly correlated with their
      supporting activity for SMO(+) leukemic cells. Knockdown of HHIP gene in stromal
      cells increased their supporting activity although control cells marginally
      supported SMO(+) leukemic cell proliferation. The demethylating agent, 5-aza-2'
      deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced
      the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This
      indicates that suppression of stromal HHIP could be associated with the
      proliferation of AML/MDS cells.

PMID- 22961060
TI  - Waldenstrom's macroglobulinemia harbors a unique proteome where Ku70 is severely
      underexpressed as compared with other B-lymphoproliferative disorders.
AB  - Waldenstrom's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative
      disorder (LPD) of post-germinal center nature. Despite the fact that the precise
      molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the
      disease is the absence of the immunoglobulin heavy chain class switch
      recombination. Using two-dimensional gel electrophoresis, we compared proteomic
      profiles of WM cells with that of other LPDs. We were able to demonstrate that WM
      constitutes a unique proteomic entity as compared with chronic lymphocytic
      leukemia and marginal zone lymphoma. Statistical comparisons of protein
      expression levels revealed that a few proteins are distinctly expressed in WM in
      comparison with other LPDs. In particular we observed a major downregulation of
      the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and
      RNA levels in an independent cohort of patients. Hence, we define a distinctive
      proteomic profile for WM where the downregulation of Ku70-a component of the non
      homologous end-joining pathway-might be relevant in disease pathophysiology.

PMID- 22961062
TI  - [The 'Surgical Deck': a new generation of integrated operational rooms for ENT].
AB  - BACKGROUND: Existing operating room concepts do not meet modern technological
      opportunities anymore. The "Surgical Deck" is supposed to represent a prototype
      for a new operating room generation. The objective of the project is to achieve a
      better integration of functions and to develop an innovative concept for a highly
      developed surgical workstation. MATERIAL AND METHODS: 3 working areas are
      defined: Surgical, Airway and Technical Cockpit. The evaluation was conducted on
      284 surgeries carried out from 01.08. 2011 to 31.01. 2012. The evaluation team
      consisted of 6 surgeons, 3 surgery nurses, 3 anesthesiologists and 4 anesthesia
      nurses. Within a detailed analysis, the data of 50 FESS surgeries were compared
      to those of a control group. RESULTS: Within the FESS group, the average slot
      time was reduced by 13%. 88.2% of those questioned assessed ergonomics as being
      better than in the conventional OR. 71.5% stated that the Surgical Deck provided
      an added value with regard to the surgical procedure. 91.3% confirmed that the
      system control required additional training. 79.3% described the cost-benefit
      ratio as appropriate. For 96% of the surgeries, respondents said that they were
      feeling adequately supported by the technology. CONCLUSION: The results show a
      clear advantage of the system architecture. The Surgical Deck may present a solid
      foundation with regard to the transfer of the system into the clinical practice.
      This is relevant for new assistance functions such as process control software or
      navigation-based collision warning systems. It is to be expected that the project
      will significantly contribute to further develop the future surgical workstation
      and its standardization.

PMID- 22961061
TI  - The t(4;14) translocation and FGFR3 overexpression in multiple myeloma:
      prognostic implications and current clinical strategies.
AB  - Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by
      genetic abnormalities, including chromosomal translocations, deletions,
      duplications and genetic mutations. Translocations involving the immunoglobulin
      heavy chain region at chromosome 14q32 are observed in approximately 40% of
      patients with MM. Translocation of oncogenes into this region may lead to their
      increased expression, contributing to disease initiation, disease progression and
      therapeutic resistance. The t(4;14) translocation is associated with upregulation
      of the fibroblast growth factor receptor 3 (FGFR3) and the myeloma SET domain
      protein. Patients with t(4;14) demonstrate an overall poor prognosis that is only
      partially mitigated by the use of the novel agents bortezomib and lenalidomide;
      as such, an unmet medical need remains for patients with this aberration.
      Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and
      these studies have led to the initiation of clinical trials. Data from these
      trials will help to determine the clinical utility of FGFR3 inhibitors for
      patients with t(4;14) MM and may pave the way for personalized medicine in
      patients with this incurable disease.

PMID- 22961063
TI  - [The new S2k AWMF guideline for the treatment of Bell's palsy in commented short
      form].
AB  - A new S2k AWMF guideline for the treatment of idiopathic facial palsy has been
      published. An accurate differential diagnosis is indispensable as 25-40% of all
      facial palsy cases are of non-idiopathic origin. It is explicitly recommended to
      treat patients with idiopathic facial palsy with steroids. Steroids favour a
      complete recovery, decrease the risk of synkinesis, autonomic sequelae and
      contractures. Adjuvant antiviral therapy cannot be recommended. On current data
      there is not sufficient evidence that the combination of steroids with antiviral
      drugs has a benefit for the patients. Even when not supported by randomized
      trials, adjuvant symptomatic therapy to protect the cornea and to avoid
      complications is recommended. There is no scientific evidence that physical
      therapy has any benefit but it should be taken into account because of
      psychological reasons. A benefit of acupuncture has not been proven. If eye
      closure remains incomplete as result of defective healing, one therapeutic option
      is lid loading of the upper eye lid. Moreover, in case of severe persistent
      palsy, several well-established microsurgical nerve and muscle plasty procedures
      are available.

PMID- 22961064
TI  - [A concept to improve wet-lab training in ENT surgery].
AB  - BACKGROUND: In literature and scientific societies no binding methodical-didactic
      recommendations or guidelines exist in order to design surgical training courses.
      The educating institutions plan, organise and evaluate the educational program on
      their own initiative. MATERIAL AND METHODS: Through a research project surgical
      training courses were investigated through structured surveys, expert discussions
      with course responsibles and trainers and analysis of participant's
      questionnaires. The investigation was performed by an pedagogical-psychological
      research institution. First implementations were installed and immediately
      included in the running process of evaluation. RESULTS: From the evaluation,
      specific alterations in the organisational and micro didactic process were
      implemented. In addition, changes in a long term process had to be implemented
      such as: (a) conception of the trainer role, (b) giving feedback and judge
      performance and (c) provide contents in a sophisticated manner. CONCLUSION: For
      advanced medical training providers a long term cooperation with a pedagogical
      institution seems to be highly advisable.

PMID- 22961065
TI  - Lobular histology and response to neoadjuvant chemotherapy in invasive breast
      cancer.
AB  - Invasive lobular carcinoma (ILC) has been reported to be less responsive to
      neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to
      determine whether ILC histology indeed predicts poor response to NAC by analyzing
      tumor characteristics such as protein expression, gene expression, and imaging
      features, and by comparing NAC response rates to those seen in IDC after
      adjustment for these factors. We combined datasets from two large prospective NAC
      trials, including in total 676 patients, of which 75 were of lobular histology.
      Eligible patients had tumors >=3 cm in diameter or pathologic documentation of
      positive nodes, and underwent serial biopsies, expression microarray analysis,
      and MRI imaging. We compared pathologic complete response (pCR) rates and breast
      conservation surgery (BCS) rates between ILC and IDC, adjusted for
      clinicopathologic factors. On univariate analysis, ILCs were significantly less
      likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the
      known differences in tumor characteristics between the two histologic types,
      including hormone receptor (HR) status, HER2 status, histological grade, and p53
      expression, accounted for this difference with the lowest pCR rates among
      HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR
      and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI
      70-gene signature, was correlated with pCR, although the small numbers of ILC in
      each group precluded significant associations. BCS rate did not differ between
      IDC and ILC after adjusting for molecular characteristics. We conclude that ILC
      represents a heterogeneous group of tumors which are less responsive to NAC than
      IDC. However, this difference is explained by differences in molecular
      characteristics, particularly HR and HER2, and independent of lobular histology.

PMID- 22961066
TI  - Can chronic multimorbidity explain the age-related differences in strength, speed
      and balance in older adults?
AB  - BACKGROUND AND AIMS: It is known that physical performance declines with age in
      general, however there remains much to be understood in terms of age-related
      differences amongst older adults across a variety of physical components (such as
      speed, strength and balance), and particularly in terms of the role played by
      multimorbidity of chronic diseases. We aimed to detect the age-related
      differences across four components of physical performance and to explore to what
      extent chronic diseases and multimorbidity may explain such differences. METHODS:
      We analyzed cross-sectional data from a population-based sample of 3323 people,
      aged 60 years and older from the SNAC-K study, Stockholm, Sweden. Physical
      performance was assessed by trained nurses using several tests (grip strength,
      walking speed, balance and chair stands). Clinical diagnoses were made by the
      examining physician based on clinical history and examination. RESULTS: Censored
      normal regression analyses showed that the 72-90+ year-old persons had 17-40%
      worse grip strength, 44-86% worse balance, 30-86% worse chair stand score, and 21
      59% worse walking speed, compared with the 60-66 year-old persons. Chronic
      diseases were strongly associated with physical impairment, and this association
      was particularly strong among the younger men. However, chronic diseases
      explained only some of the age-related differences in physical performance. When
      controlling for chronic diseases in the analyses, the age-related differences in
      physical performance changed 1-11%. CONCLUSION: In spite of the strong
      association between multimorbidity and physical impairment, chronic morbidities
      explained only a small part of the age-related differences in physical
      performance.

PMID- 22961067
TI  - Smart multifunctional core-shell nanospheres with drug and gene co-loaded for
      enhancing the therapeutic effect in a rat intracranial tumor model.
AB  - Glioblastoma with high mortality has been one of the most serious cancers
      threatening human health. Because of the present treatment limitations, there is
      an urgent need to construct a multifunctional vesicle for enhancing the treatment
      of in situ malignant glioblastoma. In our study, drug and gene co-loaded magnetic
      PLGA/multifunctional polymeric liposome (magnetic PLGA/MPLs) core-shell
      nanospheres were constructed. They were mainly self-assembled from two parts:
      hydrophobic PLGA cores that can load drugs and magnetic nanocrystals; and
      polymeric lipid shells anchored with functional molecules such as PEG chains, TAT
      peptides and RGD peptides that can help the vectors to condense the gene, prolong
      the circulation time, cross the blood brain barrier and target delivery to the
      cancer tissue. The results showed that the magnetic PLGA/MPLs nanosphere has a
      nanosized core-shell structure, can achieve sustained drug release and has good
      DNA binding abilities. Importantly, compared with the control group and other
      groups with single functionality, it can co-deliver the drug and gene into the
      same cell in vitro and show the strongest inhibiting effect on the growth of the
      in situ malignant glioblastoma in vivo. All of these results indicated that the
      different functional components of magnetic PLGA/MPLs, can form an organic whole
      and none of them can be dispensed with. The magnetic PLGA/MPLs nanosphere may be
      another option for treatment of glioblastoma.

PMID- 22961068
TI  - The interaction of carbon dioxide and hypoxia in the control of cerebral blood
      flow.
AB  - Both hypoxia and carbon dioxide increase cerebral blood flow (CBF), and their
      effective interaction is currently thought to be additive. Our objective was to
      test this hypothesis. Eight healthy subjects breathed a series of progressively
      hypoxic gases at three levels of carbon dioxide. Middle cerebral artery velocity,
      as an index of CBF; partial pressures of carbon dioxide and oxygen and
      concentration of oxygen in arterial blood; and mean arterial blood pressure were
      monitored. The product of middle cerebral artery velocity and arterial
      concentration of oxygen was used as an index of cerebral oxygen delivery. Two-way
      repeated measures analyses of variance (rmANOVA) found a significant interaction
      of carbon dioxide and hypoxia factors for both CBF and cerebral oxygen delivery.
      Regression models using sigmoidal dependence on carbon dioxide and a rectangular
      hyperbolic dependence on hypoxia were fitted to the data to illustrate this
      interaction. We concluded that carbon dioxide and hypoxia act synergistically in
      their control of CBF so that the delivery of oxygen to the brain is enhanced
      during hypoxic hypercapnia and, although reduced during normoxic hypocapnia, can
      be restored to normal levels with progressive hypoxia.

PMID- 22961069
TI  - Various forms of organic and inorganic P fertilizers did not negatively affect
      soil- and root-inhabiting AM fungi in a maize-soybean rotation system.
AB  - Arbuscular mycorrhizal (AM) fungi are key components of most agricultural
      ecosystems. Therefore, understanding the impact of agricultural practices on
      their community structure is essential to improve nutrient mobilization and
      reduce plant stress in the field. The effects of five different organic or
      mineral sources of phosphorus (P) for a maize-soybean rotation system on AM
      fungal diversity in roots and soil were assessed over a 3-year period. Total DNA
      was extracted from root and soil samples collected at three different plant
      growth stages. An 18S rRNA gene fragment was amplified and taxa were detected and
      identified using denaturing gradient gel electrophoresis followed by sequencing.
      AM fungal biomass was estimated by fatty acid methyl ester analysis. Soil P
      fertility parameters were also monitored and analyzed for possible changes
      related with fertilization or growth stages. Seven AM fungal ribotypes were
      detected. Fertilization significantly modified soil P flux, but had barely any
      effect on AM fungi community structure or biomass. There was no difference in the
      AM fungal community between plant growth stages. Specific ribotypes could not be
      significantly associated to P treatment. Ribotypes were associated with root or
      soil samples with variable detection frequencies between seasons. AM fungal
      biomass remained stable throughout the growing seasons. This study demonstrated
      that roots and soil host distinct AM fungal communities and that these are very
      temporally stable. The influence of contrasting forms of P fertilizers was not
      significant over 3 years of crop rotation.

PMID- 22961070
TI  - Glucocorticoid regulates interleukin-37 in systemic lupus erythematosus.
AB  - The aim of this study was to research the expression of IL-37 in systemic lupus
      erythematosus (SLE) patients and the effect of glucocorticoid on IL-37. Thirty
      newly diagnosed severe SLE patients receiving prednisone 1 mg/kg/day for 14
      consecutive days and 30 healthy subjects were enrolled into this study. The
      plasma levels of IL-37 and other cytokines were detected by ELISA and the
      relative mRNA amounts of IL-37 and other cytokines were detected by RT-PCR. The
      plasma levels of IL-37, IL-18, IL-18BP, IFN-gamma, and IL-6 in SLE patients
      increased significantly compared with healthy controls (p<0.05). The relative
      amount of IL-37 mRNA increased by 2.45-fold in pre-treatment SLE patients
      compared with controls (p<0.05). Plasma concentrations of IL-37 correlated with
      IL-18, IL-18BP, IFN-gamma, IL-6 and SLEDAI score in both pre-treatment and post
      treatment SLE patients. The plasma levels of IL-37 decreased significantly after
      treatment of glucocorticoid. The relative amount of IL-37 mRNA decreased by 24.5
      % in post-treatment SLE patients compared with pre-treatment ones (p<0.01). In
      conclusion, IL-37 is upregulated in active SLE patients. IL-37 is correlated with
      pro-inflammatory cytokines and SLEDAI. Glucocorticoid can downregulate the
      expression of IL-37 and other cytokines in SLE patients.

PMID- 22961071
TI  - [HIV 2012 : research update].
AB  - HIV therapy is able to achieve complete viral suppression in up to 90% of
      patients. Thus, most patients will benefit from long-term effective and tolerable
      therapy combinations. Antiretroviral therapy, however, can still lead to side
      effects, is costly, and its success is dependent on sufficient health system
      resources and access to different drug combinations. Established tools in
      prevention and novel approaches to avoid spread of HIV infection are crucial to
      combat the epidemic. Recent advances in research about how drug regimens stop
      viral transmission ("treatment as prevention"), how the immune system defends
      against HIV (natural killer cells, broad neutralizing antibodies), and how
      cellular factors restrict viral replication are import milestones on the long way
      to stopping the global epidemic and to fostering vaccine development.

PMID- 22961072
TI  - [Diabetic nephropathy].
AB  - Diabetic nephropathy can impact on quality of life, morbidity and mortality of
      affected patients. The prognosis can be improved by early diagnosis and therapy.
      The association between renal insufficiency, cardiovascular morbidity and
      mortality is of importance. Annual nephropathy screening should involve the
      analyses of albuminuria and glomerular filtration rate (GFR). After having
      detected albuminuria or reduced GFR, renal ultrasound imaging and microscopic
      examination of the urine sediment is necessary. Patients with abnormal or
      ambiguous findings should be referred to a nephrologist and may require a renal
      biopsy. Patients with renal complications can benefit from a goal-orientated
      intervention involving an antidiabetic, antihypertensive and lipid-modifying
      therapy. The avoidance of potentially nephrotoxic prescriptions and a renal
      function dependent dose-adjustment of medications are of importance in patients
      with declining renal function.

PMID- 22961073
TI  - Vitamin D and cardiovascular disease: is there evidence to support the bandwagon?
AB  - In the last 3 years, more evidence accumulated that vitamin D (vitD)deficiency
      associates with cardiovascular disease (CVD) and risk factors. The association
      with higher cardiovascular (CV) mortality was stronger than with nonfatal CVD
      events. A higher incidence of type 2 diabetes was also shown. Many factors
      related to lifestyle (physical activity in particular) influence both vitD levels
      and CVD, and may contribute to explain these observational data. Whether the
      association between vitD and CVD is causal can only be established through
      randomized controlled trials (RCTs), and to date the results of the randomized
      trials, which were not designed for investigating CV outcomes, do not support the
      association data. Answers on the effects of vitD supplementation on primary and
      secondary prevention of CV may be found in the specifically designed ongoing
      RCTs. In the mean time, low vitamin D levels should be regarded as a marker of
      unhealthy lifestyle, requiring a more aggressive attempt at modifying individual
      lifestyle.

PMID- 22961074
TI  - Differentiating primary CNS lymphoma from glioblastoma multiforme: assessment
      using arterial spin labeling, diffusion-weighted imaging, and 18F
      fluorodeoxyglucose positron emission tomography.
AB  - INTRODUCTION: Our purpose was to evaluate the diagnostic performance of arterial
      spin labeling (ASL) perfusion imaging, diffusion-weighted imaging (DWI), and
      (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in
      differentiating primary central nervous system lymphomas (PCNSLs) from
      glioblastoma multiformes (GBMs). METHODS: Fifty-six patients including 19 with
      PCNSL and 37 with GBM were retrospectively studied. From the ASL data, an
      absolute tumor blood flow (aTBF) and a relative tumor blood flow (rTBF) were
      obtained within the enhancing portion of each tumor. In addition, the minimum
      apparent diffusion coefficient (ADCmin) and the maximum standard uptake value
      (SUVmax) were obtained from DWI and FDG-PET data, respectively. Each of the four
      parameters was compared between PCNSLs and GBMs using Kruskal-Wallis test. The
      performance in discriminating between PCNSLs and GBMs was evaluated using the
      receiver-operating characteristics analysis. Area-under-the-curve (AUC) values
      were compared among the four parameters using a nonparametric method. RESULTS:
      The aTBF, rTBF, and ADCmin were significantly higher in GBMs (mean aTBF +/- SD =
      91.6 +/- 56.0 mL/100 g/min, mean rTBF +/- SD = 2.61 +/- 1.61, mean ADCmin +/- SD
      = 0.78 +/- 0.19 * 10(-3) mm(2)/s) than in PCNSLs (mean aTBF +/- SD = 37.3 +/-
      10.5 mL/100 g/min, mean rTBF +/- SD = 1.24 +/- 0.37, mean ADCmin +/- SD = 0.61 +/
      0.13 * 10(-3) mm(2)/s) (p < 0.005, respectively). In addition, SUVmax was
      significantly lower in GBMs (mean +/- SD = 13.1 +/- 6.34) than in PCNSLs (mean +/
      SD = 22.5 +/- 7.83) (p < 0.005). The AUC for aTBF (0.888) was higher than those
      for rTBF (0.810), ADCmin (0.768), and SUVmax (0.848), although their difference
      was not statistically significant. CONCLUSION: ASL perfusion imaging is useful
      for differentiating PCNSLs from GBMs as well as DWI and FDG-PET.

PMID- 22961075
TI  - Validation of the Arabic version of the EORTC quality of life questionnaire among
      cancer patients in Lebanon.
AB  - PURPOSE: The objective of this article was to evaluate the psychometric
      properties of the translated Lebanese Arabic version of the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire-C30 in a
      sample of adult cancer patients in Lebanon. METHODS: The EORTC QLQ-C30 was
      translated into Lebanese Arabic and administered to a convenient sample of 200
      adult patients diagnosed with cancer at a tertiary care center in Lebanon between
      2009 and 2010. The psychometric indices assessed were reliability, multitrait
      scaling analysis, construct validity, and confirmatory factor analysis. RESULTS:
      Six out of nine subscales had Cronbach's alpha coefficients above 0.70.
      Multitrait scaling analysis showed that all item-scale correlation coefficients
      met the set standards of convergent validity with the exception of item 5 only
      (95.8 %). In addition, 79.7 % of the item-scale correlation coefficients met the
      criterion for discriminant validity. In inter-scale correlations, all
      conceptually related scales had correlation coefficients of >= 0.40 with the
      exception of role functioning and fatigue scales having an undesirable
      correlation coefficient of -0.76. In known-groups comparison, the instrument
      differentiated significantly between some of the subscales with respect to
      education, employment, and age. CFA showed an almost good fit (GFI = 0.87) with
      respect to our current data set. CONCLUSION: The translated Lebanese Arabic
      version of the EORTC QLQ-C30 is a reliable and valid instrument that can be used
      to assess the quality of life of Lebanese cancer patients.

PMID- 22961077
TI  - Utility of 18F-fluoride PET/CT and 18F-FDG PET/CT in the detection of bony
      metastases in heightened-risk head and neck cancer patients.
AB  - This study compared the diagnostic accuracy of (18)F-FDG PET/CT with that of
      (18)F-fluoride PET/CT in the detection of bony metastases in heightened-risk head
      and neck cancer patients. METHODS: The study participants underwent (18)F-FDG
      PET/CT and (18)F-fluoride PET/CT within 2 wk of each another. RESULTS: A total of
      98 bony metastases were found in 18 of our 80 patients. (18)F-fluoride PET/CT and
      (18)F-FDG PET/CT showed similar lesion-based sensitivity (69.4% vs. 57.1%, P =
      0.126) and areas under the curve (0.7561 vs. 0.7959, P = 0.149). Their combined
      interpretation demonstrated a significantly greater sensitivity and areas under
      the curve than that obtained with either modality alone (P < 0.001) in lesion
      based analysis but not in patient-based analysis, with a treatment strategy
      change in 2 patients. CONCLUSION: (18)F-fluoride PET/CT is a feasible modality
      for detecting bony metastases in patients with head and neck cancers, with
      similar sensitivity to (18)F-FDG PET/CT. Their combined use may not be
      justifiable.

PMID- 22961078
TI  - Oral alveolar soft part sarcoma in childhood and adolescence: report of two cases
      and review of literature.
AB  - Alveolar soft part sarcoma (ASPS) constitutes a rare soft tissue malignant
      neoplasm comprising less than 1 % of all soft tissue sarcomas. ASPS demonstrates
      a strong predilection for adolescents and young adults, with a female
      predominance reported. The head and neck region is the most commonly affected
      region in pediatric patients with the tongue and orbit affected most commonly.
      Herein we present the clinical, radiographic, histopathologic,
      immunohistochemical and molecular features of two examples of ASPS affecting the
      oral cavity of 4 and 13 year-old boys, along with a focused review of the
      literature on intraoral ASPS in pediatric patients.

PMID- 22961079
TI  - Vascular endothelial growth factor-mediated islet hypervascularization and
      inflammation contribute to progressive reduction of beta-cell mass.
AB  - Type 2 diabetes (T2D) results from insulin resistance and inadequate insulin
      secretion. Insulin resistance initially causes compensatory islet hyperplasia
      that progresses to islet disorganization and altered vascularization,
      inflammation, and, finally, decreased functional beta-cell mass and
      hyperglycemia. The precise mechanism(s) underlying beta-cell failure remain to be
      elucidated. In this study, we show that in insulin-resistant high-fat diet-fed
      mice, the enhanced islet vascularization and inflammation was parallel to an
      increased expression of vascular endothelial growth factor A (VEGF). To elucidate
      the role of VEGF in these processes, we have genetically engineered beta-cells to
      overexpress VEGF (in transgenic mice or after adeno-associated viral vector
      mediated gene transfer). We found that sustained increases in beta-cell VEGF
      levels led to disorganized, hypervascularized, and fibrotic islets, progressive
      macrophage infiltration, and proinflammatory cytokine production, including tumor
      necrosis factor-alpha and interleukin-1beta. This resulted in impaired insulin
      secretion, decreased beta-cell mass, and hyperglycemia with age. These results
      indicate that sustained VEGF upregulation may participate in the initiation of a
      process leading to beta-cell failure and further suggest that compensatory islet
      hyperplasia and hypervascularization may contribute to progressive inflammation
      and beta-cell mass loss during T2D.

PMID- 22961081
TI  - Overexpression of sphingosine kinase 1 prevents ceramide accumulation and
      ameliorates muscle insulin resistance in high-fat diet-fed mice.
AB  - The sphingolipids sphingosine-1-phosphate (S1P) and ceramide are important
      bioactive lipids with many cellular effects. Intracellular ceramide accumulation
      causes insulin resistance, but sphingosine kinase 1 (SphK1) prevents ceramide
      accumulation, in part, by promoting its metabolism into S1P. Despite this, the
      role of SphK1 in regulating insulin action has been largely overlooked.
      Transgenic (Tg) mice that overexpress SphK1 were fed a standard chow or high-fat
      diet (HFD) for 6 weeks before undergoing several metabolic analyses. SphK1 Tg
      mice fed an HFD displayed increased SphK activity in skeletal muscle, which was
      associated with an attenuated intramuscular ceramide accumulation compared with
      wild-type (WT) littermates. This was associated with a concomitant reduction in
      the phosphorylation of c-jun amino-terminal kinase, a serine threonine kinase
      associated with insulin resistance. Accordingly, skeletal muscle and whole-body
      insulin sensitivity were improved in SphK1 Tg, compared with WT mice, when fed an
      HFD. We have identified that the enzyme SphK1 is an important regulator of lipid
      partitioning and insulin action in skeletal muscle under conditions of increased
      lipid supply.

PMID- 22961082
TI  - Central resistin overexposure induces insulin resistance through Toll-like
      receptor 4.
AB  - Resistin promotes both inflammation and insulin resistance associated with energy
      homeostasis impairment. However, the resistin receptor and the molecular
      mechanisms mediating its effects in the hypothalamus, crucial for energy
      homeostasis control, and key insulin-sensitive tissues are still unknown. In the
      current study, we report that chronic resistin infusion in the lateral cerebral
      ventricle of normal rats markedly affects both hypothalamic and peripheral
      insulin responsiveness. Central resistin treatment inhibited insulin-dependent
      phosphorylation of insulin receptor (IR), AKT, and extracellular signal-related
      kinase 1/2 associated with reduced IR expression and with upregulation of
      suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two
      negative regulators of insulin signaling. Additionally, central resistin promotes
      the activation of the serine kinases Jun NH(2)-terminal kinase and p38 mitogen
      activated protein kinase, enhances the serine phosphorylation of insulin receptor
      substrate-1, and increases the expression of the proinflammatory cytokine
      interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues.
      Interestingly, we also report for the first time, to our knowledge, the direct
      binding of resistin to Toll-like receptor (TLR) 4 receptors in the hypothalamus,
      leading to the activation of the associated proinflammatory pathways. Taken
      together, our findings clearly identify TLR4 as the binding site for resistin in
      the hypothalamus and bring new insight into the molecular mechanisms involved in
      resistin-induced inflammation and insulin resistance in the whole animal.

PMID- 22961084
TI  - Deregulation of protein phosphatase 2A and hyperphosphorylation of tau protein
      following onset of diabetes in NOD mice.
AB  - The histopathological hallmarks of Alzheimer disease (AD) include intraneuronal
      neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein.
      Insulin dysfunction might influence AD pathology, as population-based and cohort
      studies have detected higher AD incidence rates in diabetic patients. But how
      diabetes affects tau pathology is not fully understood. In this study, we
      investigated the impact of insulin dysfunction on tau phosphorylation in a
      genetic model of spontaneous type 1 diabetes: the nonobese diabetic (NOD) mouse.
      Brains of young and adult female NOD mice were examined, but young NOD mice did
      not display tau hyperphosphorylation. tau phosphorylation at tau-1 and pS422
      epitopes was slightly increased in nondiabetic adult NOD mice. At the onset of
      diabetes, tau was hyperphosphorylated at the tau-1, AT8, CP13, pS262, and pS422.
      A subpopulation of diabetic NOD mice became hypothermic, and tau
      hyperphosphorylation further extended to paired helical filament-1 and TG3
      epitopes. Furthermore, elevated tau phosphorylation correlated with an inhibition
      of protein phosphatase 2A (PP2A) activity. Our data indicate that insulin
      dysfunction in NOD mice leads to AD-like tau hyperphosphorylation in the brain,
      with molecular mechanisms likely involving a deregulation of PP2A. This model may
      be a useful tool to address further mechanistic association between insulin
      dysfunction and AD pathology.

PMID- 22961080
TI  - A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes
      loci in Chinese Hans.
AB  - Substantial progress has been made in identification of type 2 diabetes (T2D)
      risk loci in the past few years, but our understanding of the genetic basis of
      T2D in ethnically diverse populations remains limited. We performed a genome-wide
      association study and a replication study in Chinese Hans comprising 8,569 T2D
      case subjects and 8,923 control subjects in total, from which 10 single
      nucleotide polymorphisms were selected for further follow-up in a de novo
      replication sample of 3,410 T2D case and 3,412 control subjects and an in silico
      replication sample of 6,952 T2D case and 11,865 control subjects. Besides
      confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3,
      HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci,
      including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 * 10(
      9)) and RASGRP1 (rs7403531: P = 3.9 * 10(-9)), of which the association signal at
      GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D
      risk-increasing allele of RASGRP1-rs7403531 was also associated with higher
      HbA(1c) and lower homeostasis model assessment of beta-cell function (P = 0.03
      and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5
      rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not
      with fasting glucose. Our findings not only provide new insights into the
      pathophysiology of T2D, but may also shed light on the ethnic differences in T2D
      susceptibility.

PMID- 22961083
TI  - Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity
      to promote hyperinsulinemia in mice.
AB  - Genetic studies have revealed the association between the epsilon2 allele of the
      apolipoprotein E (apoE) gene and greater risk of metabolic diseases. This study
      compared C57BL/6 mice in which the endogenous mouse gene has been replaced by the
      human APOE2 or APOE3 gene (APOE2 and APOE3 mice) to identify the mechanism
      underlying the relationship between epsilon2 and obesity and diabetes. In
      comparison with APOE3 mice, the APOE2 mice had elevated fasting plasma lipid and
      insulin levels and displayed prolonged postprandial hyperlipidemia accompanied by
      increased granulocyte number and inflammation 2 h after being fed a lipid-rich
      meal. In comparison with APOE3 mice, the APOE2 mice also showed increased
      adiposity when maintained on a Western-type, high-fat, high-cholesterol diet.
      Adipose tissue dysfunction with increased macrophage infiltration, abundant crown
      like structures, and inflammation were also observed in adipose tissues of APOE2
      mice. The severe adipocyte dysfunction and tissue inflammation corresponded with
      the robust hyperinsulinemia observed in APOE2 mice after being fed the Western
      type diet. Taken together, these data showed that impaired plasma clearance of
      apoE2-containing, triglyceride-rich lipoproteins promotes lipid redistribution to
      neutrophils and adipocytes to accentuate inflammation and adiposity, thereby
      accelerating the development of hyperinsulinemia that will ultimately lead to
      advanced metabolic diseases.

PMID- 22961085
TI  - c-Jun NH2-terminal kinase 1/2 and endoplasmic reticulum stress as interdependent
      and reciprocal causation in diabetic embryopathy.
AB  - Embryos exposed to high glucose exhibit aberrant maturational and
      cytoarchitectural cellular changes, implicating cellular organelle stress in
      diabetic embryopathy. c-Jun-N-terminal kinase 1/2 (JNK1/2) activation is a causal
      event in maternal diabetes-induced neural tube defects (NTD). However, the
      relationship between JNK1/2 activation and endoplasmic reticulum (ER) stress in
      diabetic embryopathy has never been explored. We found that maternal diabetes
      significantly increased ER stress markers and induced swollen/enlarged ER lumens
      in embryonic neuroepithelial cells during neurulation. Deletion of either jnk1 or
      jnk2 gene diminished hyperglycemia-increased ER stress markers and ER chaperone
      gene expression. In embryos cultured under high-glucose conditions (20 mmol/L),
      the use of 4-phenylbutyric acid (4-PBA), an ER chemical chaperone, diminished ER
      stress markers and abolished the activation of JNK1/2 and its downstream
      transcription factors, caspase 3 and caspase 8, and Sox1 neural progenitor
      apoptosis. Consequently, both 1 and 2 mmol/L 4-PBA significantly ameliorated high
      glucose-induced NTD. We conclude that hyperglycemia induces ER stress, which is
      responsible for the proapoptotic JNK1/2 pathway activation, apoptosis, and NTD
      induction. Suppressing JNK1/2 activation by either jnk1 or jnk2 gene deletion
      prevents ER stress. Thus, our study reveals a reciprocal causation of ER stress
      and JNK1/2 in mediating the teratogenicity of maternal diabetes.

PMID- 22961087
TI  - Loss of TDAG51 results in mature-onset obesity, hepatic steatosis, and insulin
      resistance by regulating lipogenesis.
AB  - Regulation of energy metabolism is critical for the prevention of obesity,
      diabetes, and hepatic steatosis. Here, we report an important role for the
      pleckstrin homology-related domain family member, T-cell death-associated gene 51
      (TDAG51), in the regulation of energy metabolism. TDAG51 expression was examined
      during adipocyte differentiation. Adipogenic potential of preadipocytes with
      knockdown or absence of TDAG51 was assessed. Weight gain, insulin sensitivity,
      metabolic rate, and liver lipid content were also compared between TDAG51
      deficient (TDAG51(-/-)) and wild-type mice. In addition to its relatively high
      expression in liver, TDAG51 was also present in white adipose tissue (WAT).
      TDAG51 was downregulated during adipogenesis, and TDAG51(-/-) preadipocytes
      exhibited greater lipogenic potential. TDAG51(-/-) mice fed a chow diet exhibited
      greater body and WAT mass, had reduced energy expenditure, displayed mature-onset
      insulin resistance (IR), and were predisposed to hepatic steatosis. TDAG51(-/-)
      mice had increased hepatic triglycerides and SREBP-1 target gene expression.
      Furthermore, TDAG51 expression was inversely correlated with fatty liver in
      multiple mouse models of hepatic steatosis. Taken together, our findings suggest
      that TDAG51 is involved in energy homeostasis at least in part by regulating
      lipogenesis in liver and WAT, and hence, may constitute a novel therapeutic
      target for the treatment of obesity and IR.

PMID- 22961086
TI  - A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch
      up growth: a Randle cycle favoring fat storage.
AB  - Catch-up growth, a risk factor for type 2 diabetes, is characterized by
      hyperinsulinemia and accelerated body fat recovery. Using a rat model of
      semistarvation-refeeding that exhibits catch-up fat, we previously reported that
      during refeeding on a low-fat diet, glucose tolerance is normal but insulin
      dependent glucose utilization is decreased in skeletal muscle and increased in
      adipose tissue, where de novo lipogenic capacity is concomitantly enhanced. Here
      we report that isocaloric refeeding on a high-fat (HF) diet blunts the enhanced
      in vivo insulin-dependent glucose utilization for de novo lipogenesis (DNL) in
      adipose tissue. These are shown to be early events of catch-up growth that are
      independent of hyperphagia and precede the development of overt adipocyte
      hypertrophy, adipose tissue inflammation, or defective insulin signaling. These
      results suggest a role for enhanced DNL as a glucose sink in regulating glycemia
      during catch-up growth, which is blunted by exposure to an HF diet, thereby
      contributing, together with skeletal muscle insulin resistance, to the
      development of glucose intolerance. Our findings are presented as an extension of
      the Randle cycle hypothesis, whereby the suppression of DNL constitutes a
      mechanism by which dietary lipids antagonize glucose utilization for storage as
      triglycerides in adipose tissue, thereby impairing glucose homeostasis during
      catch-up growth.

PMID- 22961088
TI  - Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity.
AB  - Obesity is associated with chronic low-grade inflammation that contributes to
      defects in energy metabolism and insulin resistance. Suppressor of cytokine
      signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans.
      SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal
      transduction in adipose tissue and the liver. Skeletal muscle is an important
      tissue for controlling energy expenditure and whole-body insulin sensitivity;
      however, the physiological importance of SOCS3 in this tissue has not been
      examined. Therefore, we generated mice that had SOCS3 specifically deleted in
      skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development,
      body mass, adiposity, appetite, and energy expenditure compared with wild-type
      (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet,
      SOCS3 MKO mice were protected against the development of hyperinsulinemia and
      insulin resistance because of enhanced skeletal muscle insulin receptor substrate
      1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle
      glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a
      critical role in regulating muscle development or energy expenditure, but it is
      an important contributing factor for inhibiting insulin sensitivity in obesity.
      Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in
      reversing obesity-related glucose intolerance and insulin resistance.

PMID- 22961089
TI  - The analgesic effect of electroacupuncture on inflammatory pain in the rat model
      of collagenase-induced arthritis: mediation by opioidergic receptors.
AB  - Electroacupuncture (EA) is widely practiced for the treatment of osteoarthritic
      (OA) pain, but its therapeutic mechanisms have not yet been fully studied,
      especially in the experimental OA rat model. In order to induce collagenase
      induced arthritis (CIA) in rats, male Sprague-Dawley rats were intra-articularly
      injected with 0.05 ml of 4 mg/ml collagenase solution in the left knee of the
      hind limb, followed by a booster injection 4 days later. Maximal gross,
      histopathological features and biomarker activity changes consistent with human
      OA characteristics were observed four weeks after the first collagenase
      injection. In the exploratory preliminary study of EA stimulation parameters, low
      frequency train pulse EA stimulation (2 Hz, 0.07 mA, 0.3 ms) delivered to the
      Zusanli (ST36) acupoint exerted an antinociceptive effect with acupoint
      specificity in a rat model of CIA. The antinociceptive effect of Zusanli EA was
      blocked by intraperitoneal pretreatment with naloxone (MU-opioid receptor
      antagonist, 2 mg/kg) and naltrindole (delta-opioid receptor antagonist, 1 mg/kg),
      but not with norbinaltophimine (kappa-opioid receptor antagonist, 20 mg/kg). The
      synergistic antinociceptive effects of Zusanli EA were achieved with statistical
      significance by i.p. pretreatment with DAMGO (MU-opioid receptor agonist, 1
      mg/kg) and with [D-Ala2]-Deltorphin II (delta-opioid receptor agonist, 6 mg/kg),
      but not with (+/-)-U-50488 (kappa-opioid receptor agonist, 3 mg/kg). These
      results suggest that the 2-Hz EA can attenuate the osteoarthritic pain in CIA,
      and the analgesic effects of EA can be mediated by MU-opioid and delta-opioid,
      but not by kappa-opioid receptors.

PMID- 22961090
TI  - Leflunomide: friend or foe for systemic lupus erythematosus?
AB  - Leflunomide is a new immunosuppressive medicine that has been effectively used in
      the therapy of rheumatoid arthritis and subsequently used with success in animal
      models and patients with systemic lupus erythematosus (SLE). However, its use has
      also been associated with significant and serious adverse reactions involving
      hematological, hepatic, immune, dermatological and respiratory systems. In the
      current review, we attempt to describe the two sides of this drug in the
      treatment of SLE.

PMID- 22961091
TI  - Acute charcot arthropathy of the wrist in a diabetic patient.

PMID- 22961092
TI  - A randomized clinical trial to evaluate the preventive effect of cranberry juice
      (UR65) for patients with recurrent urinary tract infection.
AB  - We examined the rate of relapse, as a variable index, in patients with urinary
      tract infection (UTI) who suffered from multiple relapses when using cranberry
      juice (UR65). A randomized, placebo-controlled, double-blind study was conducted
      from October 2007 to September 2009 in Japan. The subjects were outpatients aged
      20 to 79 years who were randomly divided into two groups. One group received
      cranberry juice (group A) and the other a placebo beverage (group P). To keep the
      conditions blind, the color and taste of the beverages were adjusted. The
      subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once
      daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of
      UTI. In the group of females aged 50 years or more, there was a significant
      difference in the rate of relapse of UTI between groups A and P (log-rank test; p
      = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55
      (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study,
      cranberry juice prevented the recurrence of UTI in a limited female population
      with 24-week intake of the beverage.

PMID- 22961093
TI  - Don't judge a neuron only by its cover: neuronal function in in vitro
      developmental neurotoxicity testing.
AB  - Classical cases of developmental neurotoxicity (DNT) in humans and advances in
      risk assessment methods did not prevent the emergence of new chemicals with
      (suspected) DNT potential. Exposure to these chemicals may be related to the
      increased worldwide incidence of learning and neurodevelopmental disorders in
      children. DNT is often investigated in a traditional manner (in vivo using large
      numbers of experimental animals), whereas development of in vitro methods for DNT
      reduces animal use and increases insight into cellular and molecular mechanisms
      of DNT. Several essential neurodevelopmental processes, including proliferation,
      migration, differentiation, formation of axons and dendrites, synaptogenesis, and
      apoptosis, are already being evaluated in vitro using biochemical and
      morphological endpoints. Yet, investigation of chemical-induced effects on the
      development of functional neuronal networks, including network formation, inter-
      and intracellular signaling and neuronal network function, is underrepresented in
      DNT testing. This view therefore focuses on in vitro models and innovative
      experimental approaches for functional DNT testing, ranging from optical and
      electrophysiological measurements of intra- and intercellular signaling in neural
      stem/progenitor cells to measurements of network activity in neuronal networks
      using multielectrode arrays. The development of functional DNT assays will
      strongly support the decision-making process for measures to prevent potential
      chemical-induced adverse effects on neurodevelopment and cognition in humans. We
      therefore argue that for risk assessment, biochemical and morphological
      approaches should be complemented with investigations of neuronal (network)
      functionality.

PMID- 22961094
TI  - Increased nuclear thioredoxin-1 potentiates cadmium-induced cytotoxicity.
AB  - Cadmium (Cd) is a widely dispersed environmental agent that causes oxidative
      toxicity through mechanisms that are sensitive to thioredoxin-1 (Trx1). Trx1 is a
      cytoplasmic protein that translocates to nuclei during oxidative stress. Recent
      research shows that interaction of Trx1 with actin plays a critical role in cell
      survival and that increased nuclear Trx-1 potentiates proinflammatory signaling
      and death in cell and mouse models. These observations indicate that oxidative
      toxicity caused by low-dose Cd could involve disruption of actin-Trx1
      interaction, nuclear Trx1 translocation, and potentiation of proinflammatory cell
      death mechanisms. In this study, we investigated the role of nuclei-localized
      Trx1 in Cd-induced inflammation and cytotoxicity using in vitro and in vivo
      models. The results show that Cd stimulated nuclear translocation of Trx1 and p65
      of NF-kappaB. Elevation of Trx1 in nuclei in in vitro cells and kidney of
      transgenic mice potentiated Cd-stimulated NF-kappaB activation and cell death. Cd
      stimulated Trx1 nuclear translocation and NF-kappaB activation were inhibited by
      cytochalasin D, an inhibitor of actin polymerization, suggesting that actin
      regulates Trx1 nuclear translocation and NF-kappaB activation by Cd. A nuclear
      targeted dominant negative form of Trx1 blocked Cd-stimulated NF-kappaB
      activation and decreased cell death. Addition of zinc, known to antagonize Cd
      toxicity by increasing metallothionein, had no effect on Cd-stimulated nuclear
      translocation of Trx1 and NF-kappaB activation. Taken together, the results show
      that nuclear translocation and accumulation of redox-active Trx1 in nuclei play
      an important role in Cd-induced inflammation and cell death.

PMID- 22961095
TI  - Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic
      cystitis and impaired bladder contractions in young rats induced by acrolein, a
      urinary metabolite of cyclophosphamide.
AB  - Hemorrhagic cystitis is a common complication in children receiving
      cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary
      metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we
      investigated the effects and mechanisms of acrolein by intravesical instillation
      on urinary bladder muscle contractions and pathological alterations in rats.
      Acrolein instillation significantly increased the muscle contractions of rat
      bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions
      after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC)
      expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible
      nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in
      bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation
      increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary
      bladder. The iNOS inhibitors significantly inhibited the acrolein-increased
      nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies
      effectively inhibited the acrolein-increased NOx levels. The increased detrusor
      contractions by 1-h acrolein treatment were significantly reversed by the PKC
      inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein
      treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing
      antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively
      reversed the increased iNOS expression, decreased PKC phosphorylation, increased
      bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment.
      Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling
      pathway participates in the acrolein-triggered detrusor contraction inhibition
      and hemorrhagic cystitis. These findings may help us to find a new strategy to
      treat cyclophosphamide-induced hemorrhagic cystitis.

PMID- 22961096
TI  - Successful long-time treatment with mycophenolate-mofetil in a child with
      acquired factor VIII inhibitor.
AB  - Here, we report about a boy (age: 18 years) who developed an acquired factor VIII
      inhibitor at the age of 9 years. He presented with bleeding in his right ankle,
      multiple haematomas and a high-titer factor VIII type II inhibitor (400 BU).
      THERAPY: He received treatment with MMF (CellCept(r)), dexamethasone
      immunoglobulin pulses, and rituximab together with high dose FVIII (Hannover
      protocol). His inhibitor titer decreased rapidly, and half-life and recovery
      normalized. Inhibitor titres increased after reduction of the factor VIII dose,
      and increased further after MMF was stopped. A second treatment course with MMF
      again resulted in reduction of the titre, improvement in half life and recovery,
      and no more bleedings. Inhibitor reappeared with MMF dose reduction, again
      accompanied by severe bleeding. Additional rituximab stopped the bleedings, and
      treatment with MMF has been continued since. CONCLUSION: Although the laboratory
      parameters showed no complete remission, severe bleedings and expensive factor
      replacement could be avoided by long-term treatment with MMF.

PMID- 22961097
TI  - Changes of serum concentrations of brain-derived neurotrophic factor (BDNF)
      during treatment with venlafaxine and mirtazapine: role of medication and
      response to treatment.
AB  - INTRODUCTION: Depression, stress and antidepressant treatment have been found to
      modulate the expression of brain-derived neurotrophic factor (BDNF). Recent
      research suggests that serum BDNF concentration is reduced in depression and that
      antidepressant treatment leads to an increase in serum BDNF concentration.
      METHODS: We studied depressed patients receiving a randomized antidepressant
      treatment with either mirtazapine (n=29) or venlafaxine (n=27) for 28 days in a
      prospective design. Changes in the concentrations of serum neurotrophins in
      response to antidepressant treatment were assessed. RESULTS: There was a
      significant "treatment" by "medication" interaction effect on BDNF serum
      concentrations that indicated a decline of BDNF in venlafaxine-treated patients
      (7.82+/-3.75-7.18+/-5.64 ng/mL), while there was an increase in mirtazapine
      treated patients (7.64+/-6.23-8.50+/-5.37 ng/mL). There was a trend for a
      "treatment" by "remission" interaction with a favourable clinical course being
      related to increasing serum BDNF. DISCUSSION: Changes in BDNF serum
      concentrations as a result of antidepressant therapy depend on the antidepressant
      and potentially on the clinical course.

PMID- 22961098
TI  - Comparative study of the osteogenic differentiation capacity of human bone marrow
      and human adipose-derived stem cells under cyclic tensile stretch using
      quantitative analysis.
AB  - Studies comparing the osteogenic differentiation capacity of human bone marrow
      derived stem cells (hBMSCs) and human adipose-derived stem cells (hASCs) cultured
      in osteogenic differentiation medium have been inconclusive. Apart from chemical
      stimuli, mechanical stimuli have also been shown to be important in bone tissue
      engineering, which is referred to as functional bone tissue engineering. hBMSCs
      and hASCs have been shown to be sensitive to both chemical and mechanical
      stimuli. In an attempt to find a better seed cell in functional bone tissue
      engineering, we tried to quantify the osteogenic differentiation capacity of
      hBMSCs and hASCs under both mechanical and chemical stimuli. In this study,
      hBMSCs and hASCs were isolated from the same volunteers. Cells were cultured in
      osteogenic differentiation medium with and without exposure to cyclic tensile
      stretch (CTS). Quantitative measurement of alkaline phosphatase (ALP) activity
      revealed that the osteogenic differentiation capacity of hBMSCs was similar to
      that of hASCs in the early phase of differentiation in the CTS-stimulated groups.
      Quantitative measurement of mineralization showed that the late-phase osteogenic
      differentiation capacity of the hBMSCs was superior to that of hASCs in the CTS
      stimulated groups. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis was performed 5 and 10 days after cell culture. The results of the RT
      PCR revealed that the osteogenic differentiation capacity of hASCs was inferior
      to that of hBMSCs both in the CTS-stimulated and unstimulated groups. All the
      results showed that both hBMSCs and hASCs were sensitive to CTS during the
      osteogenic differentiation process. This study compared the osteogenic
      differentiation capacity of hBMSCs and hASCs in response to mechanical
      stimulations and has important implications for the use of stem cells in
      functional bone tissue engineering and regenerative medicine.

PMID- 22961101
TI  - Improving the accuracy and comparability of model-based economic evaluations of
      health technologies for reimbursement decisions: a methodological framework for
      the development of reference models.
AB  - Increasingly, decision analytic models are used within economic evaluations of
      health technologies (e.g., pharmaceuticals) submitted to national reimbursement
      bodies in countries like Australia and UK, where such models play a fundamental
      role in informing public funding decisions. Concerns regarding the accuracy of
      model outputs and hence the credibility of national reimbursement decisions are
      frequently raised. We propose a framework for developing reference models for
      specific diseases to inform economic evaluations of health technologies and their
      appraisal. The structure of a reference model reflects the natural history of the
      condition under study and defines the clinical events to be represented, the
      relationships between the events, and the effect of patient characteristics on
      the probability and timing of events. We contend that the use of reference models
      will improve the accuracy and comparability of public funding decisions. This can
      lead to the more efficient allocation of public funds.

PMID- 22961099
TI  - ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer
      Association Consortium.
AB  - PURPOSE: Previous studies have examined the association between ABO blood group
      and ovarian cancer risk, with inconclusive results. METHODS: In eight studies
      participating in the Ovarian Cancer Association Consortium, we determined ABO
      blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios
      and 95 % confidence intervals were calculated in each study using logistic
      regression; individual study results were combined using random effects meta
      analysis. RESULTS: Compared to blood group O, the A blood group was associated
      with a modestly increased ovarian cancer risk: (OR: 1.09; 95 % CI: 1.01-1.18; p =
      0.03). In diplotype analysis, the AO, but not the AA diplotype, was associated
      with increased risk (AO: OR: 1.11; 95 % CI: 1.01-1.22; p = 0.03; AA: OR: 1.03; 95
      % CI: 0.87-1.21; p = 0.76). Neither AB nor the B blood groups were associated
      with risk. Results were similar across ovarian cancer histologic subtypes.
      CONCLUSION: Consistent with most previous reports, the A blood type was
      associated modestly with increased ovarian cancer risk in this large analysis of
      multiple studies of ovarian cancer. Future studies investigating potential
      biologic mechanisms are warranted.

PMID- 22961100
TI  - Regular dental visits are associated with earlier stage at diagnosis for oral and
      pharyngeal cancer.
AB  - PURPOSE: Oral and pharyngeal cancer patients diagnosed at an advanced stage
      experience increased morbidity and mortality relative to those with localized
      disease. The aim of this study was to assess the impact of dental insurance
      status and regularity of dental visits on early detection of oral and pharyngeal
      cancer. METHODS: We examined the relationship of dental insurance and frequency
      of dental visits with stage at diagnosis among 441 oral and pharyngeal cancer
      cases from a population-based study of head and neck cancer. Ordinal logistic
      regression models were used to assess the association with stage, and tumor (T)
      and nodal (N) classification. RESULTS: Never or rarely going to the dentist was
      associated with being diagnosed at higher stage for oral and pharyngeal cancer
      (cumulative OR = 2.28, 95 % CI: 1.02-5.10) and oral cancer (cumulative OR = 9.17,
      95 % CI: 2.70-31.15) compared to those going to the dentist at least annually.
      Oral and pharyngeal cancer patients who went to the dentist infrequently
      (cumulative OR = 1.82, 95 % CI: 1.09-3.05) or rarely/never (cumulative OR = 3.24,
      95 % CI: 1.59-6.57) were diagnosed with a higher T classification compared with
      those who went at least annually. CONCLUSIONS: Receipt of regular dental
      examinations at least annually may reduce the public health burden of oral and
      pharyngeal cancer by facilitating earlier detection of the disease.

PMID- 22961102
TI  - A pilot study using machine learning and domain knowledge to facilitate
      comparative effectiveness review updating.
AB  - BACKGROUND: Comparative effectiveness and systematic reviews require frequent and
      time-consuming updating. RESULTS: of earlier screening should be useful in
      reducing the effort needed to screen relevant articles. METHODS: We collected
      16,707 PubMed citation classification decisions from 2 comparative effectiveness
      reviews: interventions to prevent fractures in low bone density (LBD) and off
      label uses of atypical antipsychotic drugs (AAP). We used previously written
      search strategies to guide extraction of a limited number of explanatory
      variables pertaining to the intervention, outcome, and STUDY DESIGN: We
      empirically derived statistical models (based on a sparse generalized linear
      model with convex penalties [GLMnet] and a gradient boosting machine [GBM]) that
      predicted article relevance. We evaluated model sensitivity, positive predictive
      value (PPV), and screening workload reductions using 11,003 PubMed citations
      retrieved for the LBD and AAP updates. Results. GLMnet-based models performed
      slightly better than GBM-based models. When attempting to maximize sensitivity
      for all relevant articles, GLMnet-based models achieved high sensitivities (0.99
      and 1.0 for AAP and LBD, respectively) while reducing projected screening by
      55.4% and 63.2%. The GLMnet-based model yielded sensitivities of 0.921 and 0.905
      and PPVs of 0.185 and 0.102 when predicting articles relevant to the AAP and LBD
      efficacy/effectiveness analyses, respectively (using a threshold of P >= 0.02).
      GLMnet performed better when identifying adverse effect relevant articles for the
      AAP review (sensitivity = 0.981) than for the LBD review (0.685). The system
      currently requires MEDLINE-indexed articles. CONCLUSIONS: We evaluated
      statistical classifiers that used previous classification decisions and
      explanatory variables derived from MEDLINE indexing terms to predict inclusion
      decisions. This pilot system reduced workload associated with screening 2
      simulated comparative effectiveness review updates by more than 50% with minimal
      loss of relevant articles.

PMID- 22961103
TI  - A distinctive epitheliomesenchymal biphasic tumor in the duodenum: the first case
      of duodenoblastoma?
AB  - Epitheliomesenchymal biphasic neoplasms are extremely rare in the duodenum, and
      most of these are carcinosarcomas. Miettinen et al. (Am J Surg Pathol 33:1370-7,
      2009) recently reported three cases of a novel distinctive epitheliomesenchymal
      biphasic tumor of the stomach in young adults. In view of the resemblance to
      other childhood blastomas, they proposed to refer to this entity as a
      gastroblastoma. Since none of the components were sufficiently atypical, the
      gastroblastoma seemed more comparable to this kind of tumor than carcinosarcomas
      or other aggressive and malignant biphasic tumors. This report describes a
      duodenal location of a similar epitheliomesenchymal biphasic tumor in a 22-year
      old woman. To our knowledge, this is the first reported case occurring primarily
      in the duodenum and might be the first case of "duodenoblastoma."

PMID- 22961104
TI  - Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise
      or not. Results of a 5-year prospective study.
AB  - Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as
      such, are becoming increasingly detected by mammography. There is no consensus
      yet on whether to excise these lesions or not after diagnosis on core needle
      biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June
      2009 correlating histomorphologic, radiological, and clinical features. There
      were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical
      ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had
      microcalcifications on mammography with 65.5 % (95/145) of patients undergoing
      subsequent excisional biopsies with the following findings: benign 20 % (19/95),
      ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and
      invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH
      group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 %
      (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43),
      DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ +
      invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The
      incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95)
      for the pure FEA group. This difference is statistically significant (p =
      0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure
      FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow
      up in the unexcised pure FEA did not show any malignancies. These findings
      suggest that pure FEA has a very low association with carcinoma, and these
      patients may benefit from close clinical and mammographic follow-up while the
      combined pure FEA and ADH cases may be re-excised.

PMID- 22961106
TI  - Sarcolipin is a newly identified regulator of muscle-based thermogenesis in
      mammals.
AB  - The role of skeletal muscle in nonshivering thermogenesis (NST) is not well
      understood. Here we show that sarcolipin (Sln), a newly identified regulator of
      the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, is necessary for
      muscle-based thermogenesis. When challenged to acute cold (4  degrees C), Sln(-/
      ) mice were not able to maintain their core body temperature (37  degrees C) and
      developed hypothermia. Surgical ablation of brown adipose tissue and functional
      knockdown of Ucp1 allowed us to highlight the role of muscle in NST.
      Overexpression of Sln in the Sln-null background fully restored muscle-based
      thermogenesis, suggesting that Sln is the basis for Serca-mediated heat
      production. We show that ryanodine receptor 1 (Ryr1)-mediated Ca(2+) leak is an
      important mechanism for Serca-activated heat generation. Here we present data to
      suggest that Sln can continue to interact with Serca in the presence of Ca(2+),
      which can promote uncoupling of the Serca pump and cause futile cycling. We
      further show that loss of Sln predisposes mice to diet-induced obesity, which
      suggests that Sln-mediated NST is recruited during metabolic overload. These data
      collectively suggest that SLN is an important mediator of muscle thermogenesis
      and whole-body energy metabolism.

PMID- 22961107
TI  - Early infection with respiratory syncytial virus impairs regulatory T cell
      function and increases susceptibility to allergic asthma.
AB  - Immune tolerance is instituted early in life, during which time regulatory T
      (T(reg)) cells have an important role. Recurrent infections with respiratory
      syncytial virus (RSV) in early life increase the risk for asthma in adult life.
      Repeated infection of infant mice tolerized to ovalbumin (OVA) through their
      mother's milk with RSV induced allergic airway disease in response to OVA
      sensitization and challenge, including airway inflammation, hyper-reactivity and
      higher OVA-specific IgE, as compared to uninfected tolerized control mice. Virus
      infection induced GATA-3 expression and T helper type 2 (T(H)2) cytokine
      production in forkhead box P3 (FOXP3)(+) T(reg) cells and compromised the
      suppressive function of pulmonary T(reg) cells in a manner that was dependent on
      interleukin-4 receptor alpha (IL-4Ralpha) expression in the host. Thus, by
      promoting a T(H)2-type inflammatory response in the lung, RSV induced a T(H)2
      like effector phenotype in T(reg) cells and attenuated tolerance to an unrelated
      antigen (allergen). Our findings highlight a mechanism by which viral infection
      targets a host-protective mechanism in early life and increases susceptibility to
      allergic disease.

PMID- 22961108
TI  - Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.
AB  - Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the
      most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet
      the basis of their robust protection remains poorly understood. Here we show that
      the degree of LAV-mediated protection against intravenous wild-type SIVmac239
      challenge strongly correlates with the magnitude and function of SIV-specific,
      effector-differentiated T cells in the lymph node but not with the responses of
      such T cells in the blood or with other cellular, humoral and innate immune
      parameters. We found that maintenance of protective T cell responses is
      associated with persistent LAV replication in the lymph node, which occurs almost
      exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid
      tissue-based, effector-differentiated, SIV-specific T cells that intercept and
      suppress early wild-type SIV amplification and, if present in sufficient
      frequencies, can completely control and perhaps clear infection, an observation
      that provides a rationale for the development of safe, persistent vectors that
      can elicit and maintain such responses.

PMID- 22961110
TI  - Review on the latest design of graphene-based inorganic materials.
AB  - The breathtakingly fast evolution of research on graphene and its modification
      methods in the recent 8 years has made possible the various preparations and
      applications of its derivatives. These hybrid structures exhibit excellent
      material characteristics including high carrier mobility and radiate
      recombination rate as well as long-term stability since graphene sheets possess
      super electrical conductivity, mechanical flexibility and good optical
      transparency. Besides, the versatile and fascinating properties of the
      nanostructures grown on graphene layers make it possible to fabricate high
      performance electronic, optoelectronic and catalytic devices. This review
      presents an overview of the latest design of structure, synthetic methods and
      applications of graphene-based inorganic nanocomposites. The challenges and
      perspectives of these emerging hybrid heterostructures are also discussed.

PMID- 22961109
TI  - MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial
      adaptive process that preserves insulin sensitivity in obesity.
AB  - We examined mouse models with altered adipocyte expression of mitoNEET, a protein
      residing in the mitochondrial outer membrane, to probe its impact on
      mitochondrial function and subsequent cellular responses. We found that
      overexpression of mitoNEET enhances lipid uptake and storage, leading to an
      expansion of the mass of adipose tissue. Despite the resulting massive obesity,
      benign aspects of adipose tissue expansion prevail, and insulin sensitivity is
      preserved. Mechanistically, we also found that mitoNEET inhibits mitochondrial
      iron transport into the matrix and, because iron is a rate-limiting component for
      electron transport, lowers the rate of beta-oxidation. This effect is associated
      with a lower mitochondrial membrane potential and lower levels of reactive oxygen
      species-induced damage, along with increased production of adiponectin.
      Conversely, a reduction in mitoNEET expression enhances mitochondrial respiratory
      capacity through enhanced iron content in the matrix, ultimately corresponding to
      less weight gain on a high-fat diet. However, this reduction in mitoNEET
      expression also causes heightened oxidative stress and glucose intolerance. Thus,
      manipulation of mitochondrial function by varying mitoNEET expression markedly
      affects the dynamics of cellular and whole-body lipid homeostasis.

PMID- 22961111
TI  - Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231
      cells through inhibition of Akt and Twist signaling pathway.
AB  - Breast cancer metastasis is more resistant to chemotherapy and radiotherapy than
      is cancer of the visceral tissues; therefore, new treatment strategies are
      urgently needed. Moscatilin, derived from the orchid Dendrobrium loddigesii, has
      shown anticancer activity. We evaluated the mechanism by which moscatilin
      suppresses the migration and metastasis of human breast cancer MDA-MB-231 cells
      in vitro and in vivo. We demonstrated that moscatilin significantly inhibits MDA
      MB-231 cell migration by using scratch assays and Boyden chambers.
      Transcriptional factors inducing epithelial-mesenchymal transition, such as
      Twist, Snail, and Akt, play important roles in cell migration and cancer
      metastasis. Moscatilin inhibited the mRNA and protein expression of Twist, but
      not that of Snail, and subsequently inhibited N-cadherin expression. However,
      these effects were reversed by constitutively expressing active myristoylated
      (myr)-Akt and Twist overexpression. Moscatilin also suppressed Akt
      phosphorylation. However, Akt overexpression reversed the inhibitory effects of
      moscatilin on phospho-Akt protein expression but not its effects on Twist. The
      moscatilin-mediated inhibition of cell migration was reversed by Akt and Twist
      overexpression, demonstrating that moscatilin blocked cell migration by
      inhibiting Akt and Twist. In an MDA-MB-231 metastatic animal model, moscatilin
      (100 mg/kg) significantly suppressed breast cancer metastasis to the lungs and
      reduced the number of metastatic lung nodules and lung weight without causing any
      toxicity. These results indicated that moscatilin inhibited MDA-MB-231 cell
      migration via Akt- and Twist-dependent pathways; this finding was consistent with
      moscatilin's antimetastatic activity in vivo. Therefore, moscatilin may be an
      effective compound for the prevention of human breast cancer metastasis.

PMID- 22961112
TI  - INSL4 pseudogenes help define the relaxin family repertoire in the common
      ancestor of placental mammals.
AB  - The relaxin/insulin-like (RLN/INSL) gene family comprises a group of signaling
      molecules that perform physiological roles related mostly to reproduction and
      neuroendocrine regulation. They are found on three different locations in the
      mammalian genome, which have been called relaxin family locus (RFL) A, B, and C.
      Early in placental mammalian evolution, the ancestral proto-RLN gene at the RFLB
      locus underwent successive rounds of small-scale duplications resulting in
      variable number of paralogous genes in different placental lineages. Most
      placental mammals harbor copies of the RLN2 and INSL6 paralogs in the RFLB.
      However, the origin of an additional paralog, INSL4 (also known as placentin),
      has been controversial as its phyletic distribution does not converge with its
      phylogenetic position. In principle, by searching for INSL4 genes in
      representative species of all major groups of mammals we can gain insights into
      when the gene originated and better reconstruct its evolutionary history. Here we
      identified INSL4 pseudogenes in two laurasiatherian, (alpaca and dolphin) and one
      xenarthran (armadillo) species. Phylogenetic and synteny analyses confirmed that
      the identified pseudogenes are orthologs of INSL4. According to these results,
      the proto-RLN gene in the RFLB underwent two successive tandem duplications which
      gave rise the INSL6 and INSL4 paralogs in the last common ancestor of placental
      mammals. The INSL4 gene was subsequently inactivated or lost from the genome in
      all placentals other than catarrhine primates, where its product became
      functionally relevant. Our results highlight the contribution of relatively old
      gene duplicates to the gene complement of extant species.

PMID- 22961113
TI  - Intraorbital ganglioglioma of optic nerve in a patient with neurofibromatosis
      type 1.
AB  - We report the case of an orbital optic nerve gangliogoma in a 55-year-old woman
      with neurofibromatosis type 1 (NF1). Clinical course neuroimaging findings,
      pathology, and treatment options of gangliogloma are discussed and contrasted
      with pilocytic astrocytomas of the optic nerve, a much more frequent visual
      pathway neoplasm in NF1 patients.

PMID- 22961114
TI  - Day-7 modified Rankin Scale score as the best measure of the thrombolysis direct
      effect on stroke?

PMID- 22961115
TI  - Patient-centered medical home: how it affects psychosocial outcomes for diabetes.
AB  - Fragmentation of the current U.S. health care system and the increased prevalence
      of chronic diseases in the U.S. have led to the recognition that new models of
      care are needed. Chronic disease management, including diabetes, is often
      accompanied by a myriad of associated psychosocial issues that need to be
      addressed as part of a comprehensive treatment plan. Diabetes care should be
      aligned with comprehensive whole-person health care. The patient-centered medical
      home (PCMH) has emerged as a model for enhanced primary care that focuses on
      comprehensive integrated care. PCMH demonstration projects have shown
      improvements in quality of care, patient experience, care coordination, access to
      care, and quality measures for diabetes. Key PCMH transformative features
      associated with psychosocial issues related to diabetes reviewed in this article
      include integration of mental and behavioral health, care
      management/coordination, payment reform, advanced access, and putting the patient
      at the center of health care. This article also reviews the evidence supporting
      comprehensive and integrated care for addressing psychosocial issues associated
      with diabetes in the medical home.

PMID- 22961117
TI  - Inhibition of the JAK-STAT3 signaling pathway by ganoderic acid A enhances
      chemosensitivity of HepG2 cells to cisplatin.
AB  - Ganoderic acid A is a lanostane triterpene isolated from Ganoderma lucidum. It
      has been reported to exhibit antitumor activity, which is mainly mediated through
      its inhibitory effect on nuclear transcription factor-kappaB and activator
      protein-1. But the role of ganoderic acid A in JAK-STAT3 signaling pathways is
      still unclear. In the present study, we investigated the effect of ganoderic acid
      A on the signal transducer and activator of the transcription 3 pathway and
      evaluated whether suppression of the signal transducer and activator of
      transcription 3 activity by ganoderic acid A could sensitize HepG2 cells to
      cisplatin. Our results show that ganoderic acid A significantly suppressed both
      the constitutively activated and IL-6-induced signal transducer and activator of
      transcription 3 phosphorylation in HepG2 cells. Inhibition of the signal
      transducer and activator of transcription 3 tyrosine phosphorylation was found to
      be achieved through suppression of JAK1 and JAK2. Furthermore, ganoderic acid A
      promoted cisplatin-induced cell death by enhancing the sensitivity of HepG2 cells
      to cisplatin mainly via the signal transducer and activator of transcription 3
      suppression. These observations suggest a potential therapeutic strategy of using
      ganoderic acid A in combination with chemotherapeutic agents for cancer
      treatment.

PMID- 22961116
TI  - Health and psychosocial outcomes in U.S. adult patients with diabetes from
      diverse ethnicities.
AB  - Within the United States, diabetes is a serious public health concern and
      patients with diabetes are more likely to experience clinical depression,
      psychological distress, and depressive symptoms than those without. Negative
      psychosocial factors are associated with poorer diabetes management and glycemic
      control. Overall, both the rates of diabetes and related psychological distress
      are greater for persons of diverse ethnicities than for non-Latino whites, and
      have reached epidemic proportions in certain groups. The following article will
      provide an overview across ethnicities of the rates of diabetes, health outcomes,
      psychosocial outcomes, and unique cultural and linguistic challenges that
      contribute to disparities within US diabetes patients of diverse ethnicities.
      Using this information, our hope is that health care practitioners and
      researchers alike can better respond to the psychosocial needs of ethnically
      diverse patients.

PMID- 22961118
TI  - Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han
      population: a community-based case-control study.
AB  - Aggrecanase-2 (ADAMTS5) is reported to play essential roles in the
      pathophysiology of osteoarthritis (OA). To explore the relationship between
      ADAMTS5 gene polymorphisms and primary OA, we conducted a community-based case
      control study. A total of 732 community residents aged 40-84 years participated
      in the community-based study in Northeast China. After taking physical
      examination and radiographic examination, 420 persons of the residents were
      diagnosed OA (216 women and 204 men). The other 312 individuals without any
      symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men)
      were considered as healthy controls. After obtaining the DNA of patients and
      control group, genotypes of the ADAMTS5 gene polymorphisms were determined by
      polymerase chain reaction (PCR) followed by restriction enzyme digestion (HAEIII
      for P692L in exon 7 and BSRBI for R614H in exon 5). The numbers of patients with
      different OA subtypes were also calculated. The genotype and allele frequency of
      for the exon 5C/T BSRBI polymorphism was significantly different between OA
      patients and control individuals (P = 0.001, OR = 0.701, 95% CI = 0.569-0.863).
      This difference was more obvious in cervical OA patients (P = 0.001, OR = 0.664,
      95% CI = 0.521-0.847). The mutation type of exon 5C/T BSRBI polymorphism would be
      a protective factor for OA especially for cervical OA. Our results suggest that
      the ADAMTS5 gene polymorphisms may contribute to the susceptibility of
      osteoarthritis in the Chinese Han population.

PMID- 22961119
TI  - Sternocostal involvement in chronic recurrent multifocal osteomyelitis associated
      with ulcerative colitis.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a chronic, relapsing,
      inflammatory, non-infectious disorder of the skeletal system and is of unknown
      origin. Early diagnosis of the disease is essential to exact treatment. The
      relationship between inflammatory bowel disease and CRMO is understood as
      extraintestinal rheumatic manifestations. CRMO associated with ulcerative colitis
      (UC) is very rarely reported. This case is first report of sternocostal
      involvement in CRMO associated with UC. 

PMID- 22961120
TI  - Modeling the properties of lanthanoid single-ion magnets using an effective point
      charge approach.
AB  - Herein, we present two geometrical models based on an effective point-charge
      approach to provide a full description of the lowest sublevels in lanthanoid
      single ion magnets (SIMs). The first one, named as the Radial Effective Charge
      (REC) model, evaluates the crystal field effect of spherical ligands, e.g. F(-),
      Cl(-) or Br(-), by placing the effective charge along the Ln-ligand axes. In this
      case the REC parameters are obtained fitting high-resolution spectroscopic data
      for lanthanoid halides. The second model, named as the Lone Pair Effective Charge
      (LPEC) model, has been developed in order to provide a realistic description of
      systems in which the lone pairs are not pointing directly towards the magnetic
      ion. A relevant example of this kind is provided by the
      bis(phthalocyaninato)lanthanoids [Ln(Pc)(2)](-). We show that a fit of the
      magnetic properties of the [Ln(Pc)(2)](-) (Ln = Tb, Dy, Ho, Er, Tm and Yb) allows
      us to extract the LPEC parameters for the lanthanoid complexes coordinated to
      sp(2)-nitrogens. Finally, we show that these effective corrections may be
      extrapolated to a large variety of lanthanoid and actinoid compounds, having
      either extended or molecular structures.

PMID- 22961121
TI  - The potential protective effect of tramiprosate (homotaurine) against Alzheimer's
      disease: a review.
AB  - Due to the progressive aging of the population and to the age-associated increase
      in its incidence, Alzheimer's disease (AD) will become in near future one of the
      major challenges that healthcare systems will have to face with in developed
      countries. Since the pathophysiological process of AD is thought to begin many
      years before the clinical diagnosis of dementia, in theory there is an
      opportunity for preventive therapeutic interventions. In recent years, there has
      been a growing interest, supported by a large number of experimental and
      epidemiological studies, in the beneficial effects of some natural compounds in
      preventing various age-related pathologic conditions, including brain aging and
      neurodegeneration. Homotaurine, a small aminosulfonate compound that is present
      in different species of marine red algae, has been shown, in both in vitro and in
      vivo models, to provide a relevant neuroprotective effect by its specific anti-
      amyloid activity and by its gamma-aminobutyric acid type A receptor affinity. The
      therapeutic efficacy of homotaurine in AD has been investigated in a pivotal
      Phase III clinical study that did not reach its pre-defined primary endpoints.
      However, post-hoc analyses have shown positive and significant effects of
      homotaurine on secondary endpoints and subgroups of patients, including a
      reduction in hippocampal volume loss and lower decline in memory function in the
      overall cohort, as well as a reduction in global cognitive decline in APOE4
      allele carriers, suggesting a disease-modifying effects. In this review, we will
      examine the pre-clinical and clinical evidence supporting the potential role of
      homotaurine as a promising candidate for both primary and secondary prevention of
      AD.

PMID- 22961122
TI  - A review of psychosocial factors in complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) is a disabling pain condition poorly
      understood by medical professionals. Because CRPS is particularly enigmatic, and
      has significant impact on patient function, researchers have examined
      psychological processes present among patients with this diagnosis. This
      systematic review examines psychosocial factors associated with CRPS, both
      predictors and sequelae. Our conclusions are that CRPS is associated with
      negative outcomes, both psychological (e.g., increased depression and anxiety)
      and psychosocial (e.g., reduced quality of life, impaired occupational function)
      in nature. However, research does not reveal support for specific personality or
      psychopathology predictors of the condition.

PMID- 22961123
TI  - Significant impact of transient deterioration of renal function on dosimetry in
      PRRT.
AB  - Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu
      DOTATATE as most clinically used radiopeptides, is widely used in the management
      of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the
      kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is
      significant because of reabsorption of the radiopeptide from the proximal tubuli
      and the resulting retention in the interstitium, mainly in the inner cortical
      zone. The high energy and consequently wide range in tissue of the yttrium-90
      beta particle result in high absorbed doses to the kidney cortex and medulla.
      Accurate renal dosimetry can help minimizing radiation nephropathy. We report a
      case of a 69-year-old candidate for PRRT with an acceptable kidney function at
      the time of screening. When performing (111)In-octreotide pretreatment dosimetry
      3 weeks later, we observed a drastic deterioration in kidney function, caused by
      undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney
      biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was
      canceled as our full-course BED limit is 37 Gy and the patient was switched to
      morphine analgesics. Renal function normalized after 3 months and repeated
      dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles
      (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield
      toxic kidney doses in a single therapy cycle, with an inherent risk of persistent
      renal insufficiency. All clinical factors which might influence kidney function
      should be verified at screening and before PRRT administration.

PMID- 22961124
TI  - Giant cell arteritis of the thyroid in a 69-year-old male.
AB  - We report the case of a 69-year-old Caucasian male with a histological confirmed
      diagnosis of giant cell arteritis (GCA) of the thyroid. To our knowledge this is
      the second reported case of GCA of the thyroid with a histological confirmed
      diagnosis. Unique to this case is that our patient did not have the simultaneous
      occurrence of a positive temporal artery biopsy or classic symptoms of temporal
      arteritis. The patient presented with fever of unknown origin, and fatigue.
      Laboratory reports included a sedimentation rate of >100 mm/h and C-reactive
      protein level of 17.1 mg/dL. Goiter with irregular calcifications was found on
      the computed tomography image. Temporal artery biopsy was negative. The patient
      continued to have intermittent fever after discharge and was readmitted to the
      hospital 41 days after discharge for fever and increasing fatigue. The thyroid
      was resected to rule out neoplasia. Granulomatous GCA was identified within the
      thyroid specimen.

PMID- 22961125
TI  - Percolation scaling in composites of exfoliated MoS2 filled with nanotubes and
      graphene.
AB  - Applications of films of exfoliated layered compounds in many areas will be
      limited by their relatively low electrical conductivity. To address this, we have
      prepared and characterised composites of a nano-conductor (nanotubes or graphene)
      embedded in a matrix of exfoliated MoS(2) nanosheets. Solvent exfoliation of
      MoS(2) nanosheets, followed by blending with dispersions of graphene or nanotubes
      allowed the formation of such composite films by vacuum filtration. This gave
      spatially uniform mixtures with fully tuneable nano-conductor content. By
      addition of the nano-conducting phase, it was possible to vary the electrical
      conductivity of the composite over nine orders of magnitude. For both filler
      types the conductivity followed percolation scaling laws both above and below the
      percolation threshold. In the case of SWNT-filled composites, conductivities as
      high as ~40 S m(-1) were achieved at volume fractions as low as ~4%.

PMID- 22961126
TI  - Antigen presentation under the influence of 'immune evasion' proteins and its
      modulation by interferon-gamma: implications for immunotherapy of cytomegalovirus
      infection with antiviral CD8 T cells.
AB  - Cytomegalovirus (CMV) disease with multiple organ manifestations is the most
      feared viral complication limiting the success of hematopoietic cell
      transplantation as a therapy of hematopoietic malignancies. A timely endogenous
      reconstitution of CD8 T cells controls CMV infection, and adoptive transfer of
      antiviral CD8 T cells is a therapeutic option to prevent CMV disease by bridging
      the gap between an early CMV reactivation and delayed endogenous reconstitution
      of protective immunity. Preclinical research in murine models has provided 'proof
      of concept' for CD8 T-cell therapy of CMV disease. Protection by CD8 T cells
      appears to be in conflict with the finding that CMVs encode proteins that inhibit
      antigen presentation to CD8 T cells by interfering with the constitutive
      trafficking of peptide-loaded MHC class I molecules (pMHC-I complexes) to the
      cell surface. Here, we have systematically explored antigen presentation in the
      presence of the three currently noted immune evasion proteins of murine CMV in
      all possible combinations and its modulation by pre-treatment of cells with
      interferon-gamma (IFN-gamma). The data reveal improvement in antigen processing
      by pre-treatment with IFN-gamma can almost overrule the inhibitory function of
      immune evasion molecules in terms of pMHC-I expression levels capable of
      triggering most of the specific CD8 T cells, though the intensity of stimulation
      did not retrieve their full functional capacity. Notably, an in vivo conditioning
      of host tissue cells with IFN-gamma in adoptive cell transfer recipients
      constitutively overexpressing IFN-gamma (B6-SAP-IFN-gamma mice) enhanced the
      antiviral efficiency of CD8 T cells in this transgenic cytoimmunotherapy model.

PMID- 22961127
TI  - Murine cytomegalovirus immune evasion proteins operative in the MHC class I
      pathway of antigen processing and presentation: state of knowledge, revisions,
      and questions.
AB  - Medical interest in cytomegalovirus (CMV) is based on lifelong neurological
      sequelae, such as sensorineural hearing loss and mental retardation, resulting
      from congenital infection of the fetus in utero, as well as on CMV disease with
      multiple organ manifestations and graft loss in recipients of hematopoietic cell
      transplantation or solid organ transplantation. CMV infection of transplantation
      recipients occurs consequent to reactivation of virus harbored in a latent state
      in the transplanted donor cells and tissues, or in the tissues of the
      transplantation recipient herself or himself. Hence, CMV infection is a paradigm
      for a viral infection that causes disease primarily in the immunocompromised
      host, while infection of the immunocompetent host is associated with only mild
      and nonspecific symptoms so that it usually goes unnoticed. Thus, CMV is kept
      under strict immune surveillance. These medical facts are in apparent conflict
      with the notion that CMVs in general, human CMV as well as animal CMVs, are
      masters of 'immune evasion', which during virus-host co-speciation have
      convergently evolved sophisticated mechanisms to avoid their recognition by
      innate and adaptive immunity of their respective host species, with viral genes
      apparently dedicated to serve just this purpose (Reddehase in Nat Rev Immunol
      2:831-844, 2002). With focus on viral interference with antigen presentation to
      CD8 T cells in the preclinical model of murine CMV infection, we try here to shed
      some more light on the in vivo balance between host immune surveillance of CMV
      infection and viral 'immune evasion' strategies.

PMID- 22961128
TI  - Alternative oxidase in resistance to biotic stresses: Nicotiana attenuata AOX
      contributes to resistance to a pathogen and a piercing-sucking insect but not
      Manduca sexta larvae.
AB  - The role of the alternative respiratory pathway in the protection of plants
      against biotic stress was examined in transgenic tobacco (Nicotiana attenuata)
      plants (irAOX) silenced in the expression of ALTERNATIVE OXIDASE (AOX) gene. Wild
      type and irAOX plants were independently challenged with (1) chewing herbivores
      (Manduca sexta), (2) piercing-sucking insects (Empoasca spp.), and (3) bacterial
      pathogens (Pseudomonas syringae pv tomato DC3000), showing that all these
      treatments can strongly elicit accumulation of AOX gene transcripts in wild-type
      plants. When N. attenuata chemical defenses and resistance were examined, irAOX
      plants showed wild-type levels of defense-related phytohormones, secondary
      metabolites, and resistance to M. sexta. In contrast, piercing-sucking
      leafhoppers (Empoasca spp.) caused more leaf damage and induced significantly
      higher salicylic acid levels in irAOX compared with wild-type plants in the field
      and/or glasshouse. Subsequently, irAOX plants accumulated lower levels of defense
      metabolites, 17-hydroxygeranyllinalool diterpene glycosides, caffeoylputrescine,
      and nicotine compared with wild-type plants under prolonged attack of Empoasca
      spp. in the glasshouse. Finally, an accelerated cell death phenotype was observed
      in irAOX plants infected with P. syringae, which correlated with higher levels of
      salicylic acid and hydrogen peroxide levels in pathogen-infected irAOX compared
      with wild-type leaves. Overall, the AOX-associated changes in phytohormone and/or
      redox levels appear to support the resistance of N. attenuata plants against cell
      piercing-sucking insects and modulate the progression of cell death in pathogen
      infected tissues but are not effective against rapidly feeding specialist
      herbivore M. sexta.

PMID- 22961129
TI  - Structural, functional, and evolutionary analysis of the unusually large stilbene
      synthase gene family in grapevine.
AB  - Stilbenes are a small family of phenylpropanoids produced in a number of
      unrelated plant species, including grapevine (Vitis vinifera). In addition to
      their participation in defense mechanisms in plants, stilbenes, such as
      resveratrol, display important pharmacological properties and are postulated to
      be involved in the health benefits associated with a moderate consumption of red
      wine. Stilbene synthases (STSs), which catalyze the biosynthesis of the stilbene
      backbone, seem to have evolved from chalcone synthases (CHSs) several times
      independently in stilbene-producing plants. STS genes usually form small families
      of two to five closely related paralogs. By contrast, the sequence of grapevine
      reference genome (cv PN40024) has revealed an unusually large STS gene family.
      Here, we combine molecular evolution and structural and functional analyses to
      investigate further the high number of STS genes in grapevine. Our reannotation
      of the STS and CHS gene families yielded 48 STS genes, including at least 32
      potentially functional ones. Functional characterization of nine genes
      representing most of the STS gene family diversity clearly indicated that these
      genes do encode for proteins with STS activity. Evolutionary analysis of the STS
      gene family revealed that both STS and CHS evolution are dominated by purifying
      selection, with no evidence for strong selection for new functions among STS
      genes. However, we found a few sites under different selection pressures in CHS
      and STS sequences, whose potential functional consequences are discussed using a
      structural model of a typical STS from grapevine that we developed.

PMID- 22961130
TI  - Distinct cell wall architectures in seed endosperms in representatives of the
      Brassicaceae and Solanaceae.
AB  - In some species, a crucial role has been demonstrated for the seed endosperm
      during germination. The endosperm has been shown to integrate environmental cues
      with hormonal networks that underpin dormancy and seed germination, a process
      that involves the action of cell wall remodeling enzymes (CWREs). Here, we
      examine the cell wall architectures of the endosperms of two related
      Brassicaceae, Arabidopsis (Arabidopsis thaliana) and the close relative Lepidium
      (Lepidium sativum), and that of the Solanaceous species, tobacco (Nicotiana
      tabacum). The Brassicaceae species have a similar cell wall architecture that is
      rich in pectic homogalacturonan, arabinan, and xyloglucan. Distinctive features
      of the tobacco endosperm that are absent in the Brassicaceae representatives are
      major tissue asymmetries in cell wall structural components that reflect the
      future site of radicle emergence and abundant heteromannan. Cell wall
      architecture of the micropylar endosperm of tobacco seeds has structural
      components similar to those seen in Arabidopsis and Lepidium endosperms. In situ
      and biomechanical analyses were used to study changes in endosperms during seed
      germination and suggest a role for mannan degradation in tobacco. In the case of
      the Brassicaceae representatives, the structurally homogeneous cell walls of the
      endosperm can be acted on by spatially regulated CWRE expression. Genetic
      manipulations of cell wall components present in the Arabidopsis seed endosperm
      demonstrate the impact of cell wall architectural changes on germination
      kinetics.

PMID- 22961131
TI  - Diverse roles of strigolactone signaling in maize architecture and the uncoupling
      of a branching-specific subnetwork.
AB  - Strigolactones (SLs) control lateral branching in diverse species by regulating
      transcription factors orthologous to Teosinte branched1 (Tb1). In maize (Zea
      mays), however, selection for a strong central stalk during domestication is
      attributed primarily to the Tb1 locus, leaving the architectural roles of SLs
      unclear. To determine how this signaling network is altered in maize, we first
      examined effects of a knockout mutation in an essential SL biosynthetic gene that
      encodes CAROTENOID CLEAVAGE DIOXYGENASE8 (CCD8), then tested interactions between
      SL signaling and Tb1. Comparative genome analysis revealed that maize depends on
      a single CCD8 gene (ZmCCD8), unlike other panicoid grasses that have multiple
      CCD8 paralogs. Function of ZmCCD8 was confirmed by transgenic complementation of
      Arabidopsis (Arabidopsis thaliana) max4 (ccd8) and by phenotypic rescue of the
      maize mutant (zmccd8::Ds) using a synthetic SL (GR24). Analysis of the zmccd8
      mutant revealed a modest increase in branching that contrasted with prominent
      pleiotropic changes that include (1) marked reduction in stem diameter, (2)
      reduced elongation of internodes (independent of carbon supply), and (3) a
      pronounced delay in development of the centrally important, nodal system of
      adventitious roots. Analysis of the tb1 zmccd8 double mutant revealed that Tb1
      functions in an SL-independent subnetwork that is not required for the other
      diverse roles of SL in development. Our findings indicate that in maize,
      uncoupling of the Tb1 subnetwork from SL signaling has profoundly altered the
      balance between conserved roles of SLs in branching and diverse aspects of plant
      architecture.

PMID- 22961133
TI  - Discovery of new modules in metabolic biology using ChemoMetabolomics.

PMID- 22961134
TI  - Impaired auxin biosynthesis in the defective endosperm18 mutant is due to
      mutational loss of expression in the ZmYuc1 gene encoding endosperm-specific
      YUCCA1 protein in maize.
AB  - The phytohormone auxin (indole-3-acetic acid [IAA]) plays a fundamental role in
      vegetative and reproductive plant development. Here, we characterized a seed
      specific viable maize (Zea mays) mutant, defective endosperm18 (de18) that is
      impaired in IAA biosynthesis. de18 endosperm showed large reductions of free IAA
      levels and is known to have approximately 40% less dry mass, compared with De18.
      Cellular analyses showed lower total cell number, smaller cell volume, and
      reduced level of endoreduplication in the mutant endosperm. Gene expression
      analyses of seed-specific tryptophan-dependent IAA pathway genes, maize Yucca1
      (ZmYuc1), and two tryptophan-aminotransferase co-orthologs were performed to
      understand the molecular basis of the IAA deficiency in the mutant. Temporally,
      all three genes showed high expression coincident with high IAA levels; however,
      only ZmYuc1 correlated with the reduced IAA levels in the mutant throughout
      endosperm development. Furthermore, sequence analyses of ZmYuc1 complementary DNA
      and genomic clones revealed many changes specific to the mutant, including a 2-bp
      insertion that generated a premature stop codon and a truncated YUC1 protein of
      212 amino acids, compared with the 400 amino acids in the De18. The putative,
      approximately 1.5-kb, Yuc1 promoter region also showed many rearrangements,
      including a 151-bp deletion in the mutant. Our concurrent high-density mapping
      and annotation studies of chromosome 10, contig 395, showed that the De18 locus
      was tightly linked to the gene ZmYuc1. Collectively, the data suggest that the
      molecular changes in the ZmYuc1 gene encoding the YUC1 protein are the causal
      basis of impairment in a critical step in IAA biosynthesis, essential for normal
      endosperm development in maize.

PMID- 22961136
TI  - The cure conundrum.

PMID- 22961132
TI  - Characterization of a viral synergism in the monocot Brachypodium distachyon
      reveals distinctly altered host molecular processes associated with disease.
AB  - Panicum mosaic virus (PMV) and its satellite virus (SPMV) together infect several
      small grain crops, biofuel, and forage and turf grasses. Here, we establish the
      emerging monocot model Brachypodium (Brachypodium distachyon) as an alternate
      host to study PMV- and SPMV-host interactions and viral synergism. Infection of
      Brachypodium with PMV+SPMV induced chlorosis and necrosis of leaves, reduced seed
      set, caused stunting, and lowered biomass, more than PMV alone. Toward gaining a
      molecular understanding of PMV- and SPMV-affected host processes, we used a
      custom-designed microarray and analyzed global changes in gene expression of PMV-
      and PMV+SPMV-infected plants. PMV infection by itself modulated expression of
      putative genes functioning in carbon metabolism, photosynthesis, metabolite
      transport, protein modification, cell wall remodeling, and cell death. Many of
      these genes were additively altered in a coinfection with PMV+SPMV and correlated
      to the exacerbated symptoms of PMV+SPMV coinfected plants. PMV+SPMV coinfection
      also uniquely altered expression of certain genes, including transcription and
      splicing factors. Among the host defenses commonly affected in PMV and PMV+SPMV
      coinfections, expression of an antiviral RNA silencing component, SILENCING
      DEFECTIVE3, was suppressed. Several salicylic acid signaling components, such as
      pathogenesis-related genes and WRKY transcription factors, were up-regulated. By
      contrast, several genes in jasmonic acid and ethylene responses were down
      regulated. Strikingly, numerous protein kinases, including several classes of
      receptor-like kinases, were misexpressed. Taken together, our results identified
      distinctly altered immune responses in monocot antiviral defenses and provide
      insights into monocot viral synergism.

PMID- 22961135
TI  - Sensitivity and specificity of the Screen for Child Anxiety Related Emotional
      Disorders (SCARED): a community-based study.
AB  - The aim of this cross-sectional community-based study was to examine the
      sensitivity and specificity of the Screen for Child Anxiety Related Emotional
      Disorders (SCARED) to the diagnosis of anxiety disorders (AD). Participants were
      119 students aged 9-18. Psychiatric diagnoses were assessed by a psychiatrist
      throughout a structural clinical interview (K-SADS-PL). Forty-four participants
      had positive diagnosis for at least one AD. The total score of the SCARED
      significantly differentiated anxious from non-anxious children with an optimal
      cutoff point of 22 (sensitivity = 81.8 %; specificity = 52.0 %). SCARED subscales
      of social phobia and separation anxiety disorder, but not generalized anxiety
      disorder, revealed better discrimination proprieties than total scores to screen
      for that specific disorder (p < .05). Both total and specific SCARED scores
      presented moderate sensitivity and specificity for detecting AD in a community
      sample. Investigators interested in screening for specific AD, rather than the
      group of AD, may benefit from using the specific subscales.

PMID- 22961137
TI  - Consumer gene tests poised for regulatory green light.

PMID- 22961138
TI  - Strapped for funding, medical researchers pitch to the crowd.

PMID- 22961139
TI  - Drug pipeline is flush with new options for chronic constipation.

PMID- 22961140
TI  - NIH aims to facilitate extramural research through new grants.

PMID- 22961142
TI  - Lack of BRCA testing approval creates snag for cancer trials.

PMID- 22961143
TI  - Controversial egg-producing stem cells promise better IVF.

PMID- 22961144
TI  - Drug companies look to biomarkers to salvage cancer target.

PMID- 22961145
TI  - Stop-work order creates uncertainty for Ebola drug research.

PMID- 22961146
TI  - Institutes experiment with a variety of different appeal processes.

PMID- 22961147
TI  - Exon-skipping drug pulls ahead in muscular dystrophy field.

PMID- 22961148
TI  - Straight talk with... Mark Sculpher. Interview by Kate Ravilious.
AB  - By 2014, the UK will be changing the way it regulates the price it pays for
      medicines. Currently the country's National Health Service (NHS) uses the
      Pharmaceutical Price Regulation Scheme (PPRS), which controls the maximum profit
      a drug manufacturer can make on the basis of capital investments the manufacturer
      has made. A review of this system, carried out by the UK Office of Fair Trading
      in 2007, recommended that, instead, medicines should be priced according to the
      therapeutic benefits they offer to patients-an idea known as value-based pricing
      (VBP) that has similarities to systems already used in smaller countries such as
      Australia and Canada. This pricing scheme has been embraced by the UK government,
      and negotiations on how the system will work are due to begin this month. A
      British switch to VBP could have ripple effects throughout the global
      pharmaceutical industry. Even though the UK's share of the world drug market is
      relatively small-just 3%-drug prices in the country are important because a
      quarter of national governments reference British values to determine their own
      sticker prices. One of the most influential thinkers on the UK's proposed system
      is health economist Mark     Sculpher, director of the Programme on Economic
      Evaluation and Health Technology Assessment at     the University of York. As a
      regular advisor to the UK National Institute for Health and     Clinical
      Excellence (NICE) and former chair of a task force on methods guidance for
      economic evaluation at the agency, Sculpher has had an instrumental role in
      guiding value-based decision-making in the country's healthcare system. Kate
      Ravilious met with Sculpher at his office in York to discuss the value of VBP.

PMID- 22961150
TI  - Turning a new phage.

PMID- 22961151
TI  - (Meta)analyze this: Systematic reviews might lose credibility.

PMID- 22961153
TI  - Does a beta2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist
      in the in vivo kidney?

PMID- 22961155
TI  - Technical concerns about immunoprecipitation of methylated fetal DNA for
      noninvasive trisomy 21 diagnosis.

PMID- 22961157
TI  - Protect thee from the sins of thy fathers?

PMID- 22961158
TI  - The tumor microenvironment controls drug sensitivity.

PMID- 22961159
TI  - A ROSy future for metabolic regulation of HSC division.

PMID- 22961160
TI  - Anuclear neutrophils keep hunting.

PMID- 22961161
TI  - Thinking inside the box: how T cell inhibitory receptors signal.

PMID- 22961162
TI  - A sweet spot to control complement-induced inflammation.

PMID- 22961163
TI  - Tracking the insidious course of Alzheimer's disease.

PMID- 22961164
TI  - The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis?

PMID- 22961165
TI  - The not-so-simple HDL story: A new era for quantifying HDL and cardiovascular
      risk?

PMID- 22961177
TI  - Interactions of thinning and stem height on the drought response of radial stem
      growth and isotopic composition of Norway spruce (Picea abies).
AB  - Radial stem growth and the isotopic composition of growth rings are commonly used
      to quantify the effects of droughts on trees. However, often these parameters are
      quantified only at one stem height, e.g., 1.3 m, and it is not known how
      representative this is for the whole stem. This study investigated radial growth
      at four stem heights (1.3, 5.5, 9.8 and 14 m) of 21, and wood Delta(13)C and
      delta(18)O at two heights (1.3 and 14 m) of 10 (co-)dominant Norway spruce trees
      from heavily (HT) and moderately thinned (MT) stands to assess whether different
      thinning intensities influenced the drought response of stems at different tree
      heights. Annual basal area increments (BAIs) and stable isotopes in earlywood and
      latewood were compared between thinning treatments and among the different stem
      heights. For BAIs, linear correlations with climate were analysed as well. The
      response of radial growth and isotopic composition to drought was similar at
      different stem heights in HT trees, but varied with height in MT trees, which
      were also more sensitive to climatic variations. Recovery of radial growth after
      drought was more rapid in trees from HT compared with MT stands, except for the
      topmost height. Basal area increments at breast height (1.3 m) provided good
      estimates of the volume growth response to drought for the whole stem, but not
      for its recovery. The faster recovery of radial growth at 1.3 m height of HT
      compared with MT trees after the 2003 drought was not accompanied by differences
      in recovery of isotopic composition. However, this is likely to be related to
      differences between treatments in remobilization of stored C and in tree
      structure (leaf area, root systems).

PMID- 22961178
TI  - [Treatment of haemophilia with an integrated therapeutical concept--Duisburg
      model].
AB  - A top quality, effective treatment of haemophilia requires an integrated
      therapeutical concept and an excellent cooperation of an interdisciplinary team.
      Since years different models are discussed in Germany in order to enlarge the
      offers for a suitable care of patients with hard to treat diseases. The health
      political targets are expressed in the changes of the Code of Social Law number V
      (SGB V) and in innovations in the statutory health insurance. This new legal
      basis provides opportunities to implement innovative treatment concepts outside
      university hospitals and paves the way for ambulant haemophilia centres to offer
      an integral care, all legally saved by a contract.  The Coagulation Centre Rhine
      Ruhr reveals as an example how haemophilia treatment in accordance with
      guidelines and with the latest results of international research can be realise
      in an ambulatory network.

PMID- 22961179
TI  - Effects of mining-derived metals on riffle-dwelling crayfish in southwestern
      Missouri and southeastern Kansas, USA.
AB  - Riffle-dwelling crayfish populations were sampled at 16 sites in 4 tributaries of
      the Spring River located within the Tri-State Mining District in southwest
      Missouri. Crayfish density, physical habitat quality, and water quality were
      examined at each site to assess the ecological effects of mining-derived metals
      on crayfish. Metals (lead, zinc, and cadmium) were analyzed in samples of surface
      water, sediment, detritus, and whole crayfish. Sites were classified a posteriori
      into reference, mining, and downstream sites primarily based on metal
      concentrations in the materials analyzed. Three species of crayfish (Orconectes
      neglectus neglectus, O. macrus, and O. virilis) were collected during the study;
      however, only O. n. neglectus was collected at all sites. Mean crayfish densities
      were significantly lower at mining sites than at reference sites. Mean
      concentrations of metals were significantly correlated among the materials
      analyzed and were significantly greater at mining and downstream sites than at
      reference sites. Principal component analyses showed a separation of sites due to
      an inverse relationship among crayfish density, metals concentrations, and
      physical habitat quality variables. Sediment probable-effects quotients and
      surface-water toxic unit scores were significantly correlated; both indicated
      risk of toxicity to aquatic biota at several sites. Metals concentrations in
      whole crayfish at several sites exceeded concentrations known to be toxic to
      carnivorous wildlife. Mining-derived metals have the potential to impair
      ecosystem function through decreased organic matter processing and nutrient
      cycling in streams due to decreased crayfish densities.

PMID- 22961180
TI  - Involvement of the WNT and FGF signaling pathways in non-isolated anorectal
      malformations: sequencing analysis of WNT3A, WNT5A, WNT11, DACT1, FGF10, FGFR2
      and the T gene.
AB  - Anorectal malformations (ARMs) comprise a broad spectrum of anomalies, including
      anal atresia, congenital anal fistula and persistence of the cloaca. Research
      suggests that genetic factors play an important role in ARM development. However,
      few genetic variants have been identified. Embryogenesis is orchestrated by
      crosstalk of the wingless-type MMTV integration site family (WNT) and fibroblast
      growth factor (FGF) signaling pathways in a process that involves several
      intracellular cascades. Studies in mice have implicated several genes from these
      pathways in the etiology of ARMs. We performed sequencing analysis of seven of
      these previously reported genes in 78 patients with ARMs occurring within the
      context of at least one additional congenital anomaly. No associations were
      identified with variants in WNT3A, WNT5A, WNT11, DACT1, FGF10 or the T gene. In
      the FGFR2 gene, three novel heterozygous nucleotide substitutions were
      identified. Further investigations, including the study of family members,
      revealed that these variants were not causally related to the phenotype in the
      present ARM cohort. Mutations in the seven investigated genes may nonetheless be
      a cause of ARMs in rare cases. However, further studies should consider genes
      encoding other proteins in the WNT/FGF signaling pathways as possible candidates.

PMID- 22961181
TI  - What are the differences between the tuberculin skin test and the QuantiFERON-TB
      Gold test?

PMID- 22961185
TI  - Acute transverse myelitis: demyelinating, inflammatory, and infectious
      myelopathies.
AB  - Acute transverse myelitis is a rare neurologic condition that has an estimated
      incidence of up to 3 per 100,000 patient years (0.003%). Although rare, acute
      transverse myelitis can have devastating neurologic effects with up to two-thirds
      of patients having a moderate to severe degree of residual disability. The term
      acute transverse myelitis was previously reserved for idiopathic cases, but
      currently is used to encompass the general clinical syndrome, whether or not the
      cause is known. Once adequate neuroimaging has ruled out a compressive etiology,
      and a lumbar puncture has demonstrated signs of inflammation within the
      cerebrospinal fluid, a workup of causes for an acute transverse myelitis must be
      undertaken. Determining the etiology of transverse myelitis can be challenging
      because there are autoimmune, inflammatory, and infectious diseases associated
      with acute transverse myelitis. The authors discuss an approach to acute
      transverse myelitis including clinical symptoms, neuroimaging, and biomarkers
      that may aid the clinician in diagnosis.

PMID- 22961186
TI  - Inherited myelopathies.
AB  - Inherited myelopathies are a small, but important subset of diseases that cause
      dysfunction of the spinal cord. Manifestations can include various combinations
      of signs and symptoms, including disturbance of gait, spasticity, paraplegia,
      amyotrophy, sensory loss, and urinary sphincter dysfunction. These diseases can
      be divided into classes that include (1) distal axonopathies-exemplified by
      hereditary spastic paraplegia, (2) motor neuron diseases including familial
      amyotrophic lateral sclerosis and spinal muscular atrophy, (3) inborn errors of
      metabolism such as adrenomyeloneuropathy, and (4) other inherited diseases with
      myelopathy as part of their spectrum of manifestations. Although the inherited
      myelopathies are relatively rare diseases, knowledge of them and their
      manifestations is important for the physician faced with a patient with
      myelopathy, particularly if there are similarly affected individuals in the
      patient's family. In addition, understanding the pathophysiologic underpinnings
      of these diseases provides insight into the molecular biology of the nervous
      system and provides a gateway toward developing treatments for these diseases.

PMID- 22961187
TI  - Metabolic and toxic myelopathies.
AB  - The myelopathies discussed in this article have an underlying metabolic or toxic
      etiology. They have many clinical, electrophysiologic, and neuropathologic
      similarities. Preferential involvement of the dorsal columns and/or corticospinal
      tracts is commonly seen. Variable degrees of peripheral nerve and/or optic nerve
      involvement may be present. In the presence of clinical or electrophysiologic
      evidence of peripheral nerve involvement, the term myeloneuropathy is commonly
      used. The metabolic and toxic myelopathies discussed here are divided into three
      categories: disorders due to an identified nutrient deficiency such as the
      subacute combined degeneration of cobalamin/vitamin B12 or copper deficiency,
      disorders that have a geographical predilection and are due to a suspected toxin
      such as lathyrism, and disorders due to a possible toxin but without a
      geographical predilection such as hepatic myelopathy (Table 1).

PMID- 22961188
TI  - Neoplastic myelopathy.
AB  - Neoplastic myelopathy may be due to external compression or to direct
      intraparenchymal involvement of the spinal cord. In this review, the authors
      discuss the most common cause for compressive neoplastic myelopathy, metastatic
      disease. They also review other compressive lesions and discuss primary
      intramedullary spinal tumors. In the acute setting, compressive metastatic
      disease should be treated with high-dose steroids when clinically necessary;
      surgery should be considered for selected patients, followed by radiation
      therapy. For most primary intramedullary spinal tumors, surgical resection
      remains the standard initial therapy. Patients with incomplete resection of
      infiltrative tumors, high-grade pathology, or recurrent tumors may benefit from
      radiation, but most spinal tumors are relatively insensitive to traditional
      chemotherapy. Neoplastic myelopathy from either compressive or intraparenchymal
      causes remains a diagnostic and therapeutic challenge. In complex cases, referral
      to a specialty center with access to neurosurgeons, neuroradiologists,
      neuropathologists, and neurooncologists is recommended.

PMID- 22961189
TI  - Vascular myelopathies.
AB  - Vascular abnormalities of the spinal cord are an important cause of myelopathy.
      Clinicians need to be aware of these disorders as they can present with a variety
      of neurologic symptoms ranging from acute spinal neurologic emergencies,
      relapsing/remitting spells to gradually progressive dysfunction. The unique
      topography and vascular anatomy of the spinal cord lends to the variety of
      clinical presentations. Both ischemic and hemorrhagic insults can occur.
      Increased clinical suspicion, better detection with newer imaging modalities and
      early treatment can often impact outcomes. The authors review clinical diagnoses,
      novel imaging, and advanced treatment modalities for the most common causes of
      vascular myelopathy.

PMID- 22961190
TI  - Infectious etiologies of myelopathy.
AB  - Myelopathy refers to a spinal cord disorder that presents with motor and/or
      sensory deficits. Infectious agents that cause myelopathy do so by either direct
      infection of neural structures (e.g., polio), a parainfectious mechanism (with a
      presumed autoimmune pathogenesis), or as a result of involvement of structures
      adjoining the spinal cord, which may cause a compressive myelopathy. This review
      of infectious causes of myelopathy focuses on pathogens that are most relevant to
      clinicians in North America.

PMID- 22961191
TI  - Management of chronic myelopathy symptoms and activities of daily living.
AB  - Many disorders can injure the spinal cord resulting in long-term chronic
      myelopathy. Spinal cord dysfunction influences the homeostasis of multiple organ
      systems ranging from the heart or lung to the integument, thus presenting a wide
      variety of challenges for medical management. Although most of our knowledge
      about the consequences of myelopathies derives from the study of traumatic spinal
      cord injuries, similar complications occur in myelopathies of all etiologies. The
      authors survey some of the important clinical issues that the general neurologist
      needs to consider in caring for patients with chronic spinal cord disease.

PMID- 22961193
TI  - Revealing genetic diversity of tree peonies at micro-evolution level with hyper
      variable chloroplast markers and floral traits.
AB  - KEY MESSAGE: Highly variable regions of chloroplast genome were found to be
      useful in the detection of plant genetic diversity at micro-evolution level. Our
      methodology will improve understanding and conservation of plant diversity. Tree
      peonies are famous flowers with about 2,000 cultivars in the world, belonging to
      Paeonia sect. Moutan of the Paeoniaceae. They are traditionally classified based
      on flower forms and colors. Due to the limited number of DNA and morphological
      markers, and the existence of synonyms and homonyms, evaluation on genetic
      diversity of so many cultivars remains a challenge. In most cases, it is
      difficult and even impossible to discriminate tree peony cultivars when they are
      not in flower. In this study, single nucleotide polymorphism detected from the
      hyper-variable regions of chloroplast genome was employed to separate tree peony
      cultivars into different maternal lineages which can be expressed briefly by a
      nucleotide molecular formula. Our approach enabled a much higher resolution of
      cultivar identification and classification that has not been obtained before. The
      newly developed hyper-variable chloroplast markers, as an independent source of
      taxonomic characteristics, provided novel evidences and higher resolution ability
      that are helpful in building an effective classification system for evaluation,
      conservation, and utilization of the tree peony germplasm resources at cultivar
      level.

PMID- 22961192
TI  - Growth differentiation factor 15 in heart failure: an update.
AB  - Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine
      expressed in the cardiovascular system. GDF-15 is emerging as a biomarker of
      cardiometabolic risk and disease burden. GDF-15 integrates information from
      cardiac and extracardiac disease pathways that are linked to the incidence,
      progression, and prognosis of heart failure (HF). Increased circulating levels of
      GDF-15 are associated with an increased risk of developing HF in apparently
      healthy individuals from the community. After an acute coronary syndrome,
      elevated levels of GDF-15 are indicative of an increased risk of developing
      adverse left ventricular remodeling and HF. In patients with established HF, the
      levels of GDF-15 and increases in GDF-15 over time are associated with adverse
      outcomes. The information provided by GDF-15 is independent of established risk
      factors and cardiac biomarkers, including BNP. More studies are needed to
      elucidate how the information provided by GDF-15 can be used for patient
      monitoring and formulating treatment decisions. Further understanding of the
      pathobiology of GDF-15 may lead to the discovery of new treatment targets in HF.

PMID- 22961194
TI  - Hepatobiliary resection with concomitant resection of the inferior vena cava for
      advanced intrahepatic cholangiocarcinoma: report of a case.
AB  - A 65-year-old female was diagnosed with intrahepatic cholangiocarcinoma involving
      the inferior vena cava (IVC). The patient underwent right trisectionectomy and
      caudate lobectomy with bile duct resection and concomitant resection of the IVC.
      The IVC was reconstructed using the right external iliac vein. Histologically,
      the tumor had invaded the IVC. Despite the administration of postoperative
      prophylactic anticoagulant therapy, IVC thrombosis developed, probably due to the
      difference in diameter between the IVC and the graft. Following the development
      of collateral vessels, the patient was discharged and is now healthy without
      recurrence 18 months after surgery. IVC reconstruction using an external iliac
      vein graft may lead to the development of IVC thrombosis. Therefore, the graft
      used for IVC reconstruction should be very carefully selected.

PMID- 22961197
TI  - Amidine- and amidinate-functionalised N-heterocyclic carbene complexes of silver
      and chromium.
AB  - A new family of N,N'-bis-(2,6-diisopropylphenyl)-(2,6-diisopropylphenyl
      imidazolium)-acetamidines have been developed as NHC proligands and ligands that
      are functionalised with neutral amidine and anionic amidinato moieties. On
      coordination they adopt diverse binding modes, depending on the nature of the
      metal and the reaction conditions. In the Ag, K and Cr complexes reported in this
      paper, monodentate kappa(1)(NHC), bimetallic bridging-(kappa(1)-NHC-kappa(1)
      amidinato) and bidentate (kappa(1)-NHC-kappa(1)-amidinato) binding modes were
      observed, respectively. Two of the novel Cr complexes, in the presence of
      activators, were tested as catalysts for the polymerisation of ethylene showing
      low activity.

PMID- 22961196
TI  - Lateral internal sphincterotomy versus 0.25 % isosorbide dinitrate ointment for
      chronic anal fissures: a prospective randomized controlled trial.
AB  - PURPOSE: To compare the healing properties of lateral internal sphincterotomy
      (LIS) and isosorbide dinitrate (ISDN) ointment for chronic anal fissure. METHODS:
      Patients with a chronic anal fissure were randomly assigned to a group treated
      with ISDN ointment (n = 105) or a group treated with LIS (n = 102). The same
      investigators examined the patients in a blinded manner, 1, 2, 3, 6, and 12
      months after the treatments. RESULTS: The anal fissure had healed completely by 4
      weeks in 64.7 versus 92.2 %, and by 6 months in 77.1 versus 97.1 % of the ISDN
      and LIS group patients, respectively. At 12 months, the recurrence rates were 4.8
      versus 1 % for the ISDN and LIS groups, respectively, and the success rates of
      the treatments were 72.4 versus 96.1 %, respectively. Six patients in the LIS
      group experienced minor fecal incontinence, and seven (6.7 %) patients in the
      ISDN group experienced headaches that responded well to paracetamol. CONCLUSION:
      ISDN ointment was reported by all patients to be easy to use. Although its
      success rate was lower than that of surgery, ISDN can be offered to selected
      patients with a chronic anal fissure, as it has a low recurrence rate and rare
      side effects are rare.

PMID- 22961195
TI  - Recent approaches to identifying biomarkers for high-risk stage II colon cancer.
AB  - The use of adjuvant chemotherapy for stage II colon cancer remains controversial.
      The accurate assessment of the risk factors associated with recurrence in
      patients with stage II disease is the key to identifying the patients that are
      most likely to benefit from adjuvant chemotherapy. Recent guidelines advocate
      that adjuvant chemotherapy for high-risk stage II colon cancer should take into
      account factors such as the T stage, number of lymph nodes examined, tumor
      differentiation, and tumor perforation. In addition to these clinicopathological
      factors, there has also been intense interest in the identification of new
      prognostic or predictive biomarkers that can improve outcomes through better
      patient classification and selection for adjuvant chemotherapy. Recent advances
      in the field of molecular genetics have led to the identification of specific
      biomarkers involved in colorectal cancer progression, whereas gene expression
      microarray technology has led to the identification of molecular profiles able to
      predict recurrence or benefit from adjuvant chemotherapy. However, none of these
      has yet been validated in large prospective clinical trials. In this article, we
      review the current status of prognostic and predictive biomarkers for stage II
      colon cancer and provide an update on the most recent developments.

PMID- 22961198
TI  - Viral infection resistance conferred on mice by siRNA transgenesis.
AB  - RNA interference is an attractive strategy to fight against viral diseases by
      targeting the mRNA of viral genes. Most studies have reported the transient
      delivery of small interfering RNA or small hairpin (shRNA) expression constructs.
      Here, we present the production of transgenic mice stably expressing shRNA or
      miRNA targeting the IE180 mRNA (immediate early gene) of the pseudorabies virus
      (PRV) which infects mice and farm animals. We firstly designed non-retroviral
      shRNA or miRNA expression vectors. Secondly, we selected the most efficient shRNA
      construct that targeted either the 5'part or 3'UTR of the IE mRNA and was able to
      knockdown the target gene expression in cultured cells, by measuring
      systematically the shRNA content and comparing this with the interfering effects.
      We then produced four lines of transgenic mice expressing different amounts of
      shRNA or miRNA in the brain but without signs of stimulation of innate immunity.
      Lastly, we tested their resistance to PRV infection. In all transgenic lines, we
      observed a significant resistance to viral challenge, the best being achieved
      with the shRNA construct targeting the 3'UTR of the IE gene. Viral DNA levels in
      the brains of infected mice were always lower in transgenic mice, even in animals
      that did not survive. Finally, this work reports an effective strategy to
      generate transgenic animals producing shRNA from non-retroviral expression
      vectors. Moreover, these mice are the first transgenic animal models producing
      shRNA with a significant antiviral effect but without any apparent shRNA
      toxicity.

PMID- 22961199
TI  - Generation of gene-targeted mice using embryonic stem cells derived from a
      transgenic mouse model of Alzheimer's disease.
AB  - Gene-targeting technology using mouse embryonic stem (ES) cells has become the
      "gold standard" for analyzing gene functions and producing disease models.
      Recently, genetically modified mice with multiple mutations have increasingly
      been produced to study the interaction between proteins and polygenic diseases.
      However, introduction of an additional mutation into mice already harboring
      several mutations by conventional natural crossbreeding is an extremely time- and
      labor-intensive process. Moreover, to do so in mice with a complex genetic
      background, several years may be required if the genetic background is to be
      retained. Establishing ES cells from multiple-mutant mice, or disease-model mice
      with a complex genetic background, would offer a possible solution. Here, we
      report the establishment and characterization of novel ES cell lines from a mouse
      model of Alzheimer's disease (3xTg-AD mouse, Oddo et al. in Neuron 39:409-421,
      2003) harboring 3 mutated genes (APPswe, TauP301L, and PS1M146V) and a complex
      genetic background. Thirty blastocysts were cultured and 15 stable ES cell lines
      (male: 11; female: 4) obtained. By injecting these ES cells into diploid or
      tetraploid blastocysts, we generated germline-competent chimeras. Subsequently,
      we confirmed that F1 mice derived from these animals showed similar biochemical
      and behavioral characteristics to the original 3xTg-AD mice. Furthermore, we
      introduced a gene-targeting vector into the ES cells and successfully obtained
      gene-targeted ES cells, which were then used to generate knockout mice for the
      targeted gene. These results suggest that the present methodology is effective
      for introducing an additional mutation into mice already harboring multiple
      mutated genes and/or a complex genetic background.

PMID- 22961200
TI  - A convective replica-exchange method for sampling new energy basins.
AB  - Replica-exchange is a powerful simulation method for sampling the basins of a
      rugged energy landscape. The replica-exchange method's sampling is efficient
      because it allows replicas to perform round trips in temperature space, thereby
      visiting both low and high temperatures in the same simulation. However, replicas
      have a diffusive walk in temperature space, and the round trip rate decreases
      significantly with the system size. These drawbacks make convergence of the
      simulation even more difficult than it already is when bigger systems are
      tackled. Here, we present a simple modification of the exchange method. In this
      method, one of the replicas steadily raises or lowers its temperature. We tested
      the convective replica-exchange method on three systems of varying complexity:
      the alanine dipeptide in implicit solvent, the GB1 beta-hairpin in explicit
      solvent and the Abeta(25-35) homotrimer in a coarse grained representation. For
      the highly frustrated Abeta(25-35) homotrimer, the proposed "convective" replica
      exchange method is twice as fast as the standard method. It discovered 24 out of
      27 free-energy basins in less than 500 ns. It also prevented the formation of
      groups of replicas that usually form on either side of an exchange bottleneck,
      leading to a more efficient sampling of new energy basins than in the standard
      method.

PMID- 22961201
TI  - Micro-wires self-assembled and 3D-connected with the help of a nematic liquid
      crystal.
AB  - We discuss a method for producing automatic 3D connections at right places
      between substrates in front of one another. The idea is based on the
      materialization of disclination lines working as templates. The lines are first
      created in the nematic liquid crystal (5CB) at the very place where microwires
      have to be synthesized. Due to their anchoring properties, colloids dispersed
      into the nematic phase produce orientational distortions around them. These
      distortions, which may be considered as due to topological charges, result in a
      nematic force, able to attract the colloids towards the disclinations.
      Ultimately, the particles get trapped onto them, forming micro- or nano
      necklaces. Before being introduced in the nematic phase, the colloids are covered
      with an adhering and conducting polypyrrole film directly synthesized at the
      surface of the particles (heterogeneous polymerization). In this manner, the
      particles become conductive so that we may finally perform an
      electropolymerization of pyrrole monomers solved in 5CB, and definitely stick the
      whole necklace. The electric connection thus synthesized is analyzed by AFM, and
      its strength is checked by means of hydrodynamic tests. This wiring method could
      allow Moore's law to overcome the limitations that arise when down-sizing the
      electronic circuits to nanometer scale.

PMID- 22961202
TI  - Ultrasensitive detection of toxic cations through changes in the tunnelling
      current across films of striped nanoparticles.
AB  - Although multiple methods have been developed to detect metal cations, only a few
      offer sensitivities below 1 pM, and many require complicated procedures and
      sophisticated equipment. Here, we describe a class of simple solid-state sensors
      for the ultrasensitive detection of heavy-metal cations (notably, an
      unprecedented attomolar limit for the detection of CH(3)Hg(+) in both
      standardized solutions and environmental samples) through changes in the
      tunnelling current across films of nanoparticles (NPs) protected with striped
      monolayers of organic ligands. The sensors are also highly selective because of
      the ligand-shell organization of the NPs. On binding of metal cations, the
      electronic structure of the molecular bridges between proximal NPs changes, the
      tunnelling current increases and highly conductive paths ultimately percolate the
      entire film. The nanoscale heterogeneity of the structure of the film broadens
      the range of the cation-binding constants, which leads to wide sensitivity ranges
      (remarkably, over 18 orders of magnitude in CH(3)Hg(+) concentration).

PMID- 22961204
TI  - Brief history of quality movement in US healthcare.
AB  - The current healthcare quality improvement infrastructure is a product of a
      century long experience of cumulative efforts. It began with an acknowledgement
      of the role of quality in healthcare, and gradually evolved to encompass the
      prioritization of quality improvement and the development of systems to monitor,
      quantify, and incentivize quality improvement in healthcare. We review the
      origins and the evolution of the US healthcare quality movement, identify
      existing initiatives specific to musculoskeletal care, outline significant
      challenges and opportunities, and propose recommendations for the future.
      Elements noted to be associated with successful healthcare quality improvement
      efforts include the presence of physician leadership, infrastructural support,
      and prioritization of healthcare quality within the culture of the organization.
      Issues that will require continued work include the development of a valid and
      reliable evidence base, accurate and replicable performance measurement and data
      collection methods, and development of a standard set of specialty specific
      performance metrics, with accurate provider attribution, risk adjustment and
      reporting mechanisms.

PMID- 22961203
TI  - Graphene field-effect transistors as room-temperature terahertz detectors.
AB  - The unique optoelectronic properties of graphene make it an ideal platform for a
      variety of photonic applications, including fast photodetectors, transparent
      electrodes in displays and photovoltaic modules, optical modulators, plasmonic
      devices, microcavities, and ultra-fast lasers. Owing to its high carrier
      mobility, gapless spectrum and frequency-independent absorption, graphene is a
      very promising material for the development of detectors and modulators operating
      in the terahertz region of the electromagnetic spectrum (wavelengths in the
      hundreds of micrometres), still severely lacking in terms of solid-state devices.
      Here we demonstrate terahertz detectors based on antenna-coupled graphene field
      effect transistors. These exploit the nonlinear response to the oscillating
      radiation field at the gate electrode, with contributions of thermoelectric and
      photoconductive origin. We demonstrate room temperature operation at 0.3 THz,
      showing that our devices can already be used in realistic settings, enabling
      large-area, fast imaging of macroscopic samples.

PMID- 22961205
TI  - Effect of a novel mutation in a Delta9-stearoyl-ACP-desaturase on soybean seed
      oil composition.
AB  - Soybean [Glycine max (L.) Merr.] oil typically contains 2-4% stearic acid. Seed
      oil with 20% stearic acid would be useful for solid fat applications, both for
      its cooking properties and health benefits. Breeding lines with high stearic acid
      have been developed, but many suffer from agronomic problems. This study
      identifies a new source of high stearic acid, determines its relationship with
      another high stearic locus and presents molecular markers for it is use in
      breeding. TCJWB03-806-7-19, a 'Holladay' mutant with high stearic acid, was
      crossed to two FAM94-41-derived lines that contained a point mutation in a seed
      specific isoform of a Delta9-stearoyl-acyl carrier protein-desaturase (SACPD-C).
      Fatty acid analysis was performed over two growing seasons with F(2)-derived
      lines and transgressive segregation for stearic acid content was observed.
      Sequencing of SACPD isoforms in TCJWB03-806-7-19 revealed the deletion of an 'A'
      nucleotide in exon 3 of SACPD-B, which results in a protein whose final 28 amino
      acids are predicted to differ from Williams 82 SACPD-B. Sorting intolerant from
      tolerant (SIFT) analysis revealed that this frameshift mutation may affect SACPD
      B protein function. Allele-specific genotyping for the SACPD-C point mutation and
      SACPD-B nucleotide deletion was performed in both populations. Additive effects
      and R(2) for stearic acid were +3.3 and 0.55 for SACPD-C and +1.9 and 0.19 for
      SACPD-B. Average stearic acid in lines homozygous for both mutations was 14.6%.
      This SACPD-B mutation represents a novel high stearic allele.

PMID- 22961206
TI  - Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of
      the bladder.
AB  - BACKGROUND AND OBJECTIVES: Long intergenic non-coding RNAs (lincRNAs) are a class
      of non-coding RNAs that regulate gene expression via chromatin reprogramming.
      Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin
      modifying complexes and plays roles in gene regulation. In this study, we
      determined the expression patterns of TUG1 and the cell proliferation inhibition
      and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder.
      METHODS: The expression levels of TUG1 were determined using Real-Time qPCR in a
      total of 44 patients with bladder urothelial carcinomas. Bladder urothelial
      carcinoma T24 and 5637 cells were transfected with TUG1 siRNA or negative control
      siRNA. Cell proliferation was evaluated using MTT assay. Apoptosis was determined
      using ELISA assay. RESULTS: TUG1 was up-regulated in bladder urothelial carcinoma
      compared to paired normal urothelium. High TUG1 expression levels were associated
      with high grade and stage carcinomas. Cell proliferation inhibition and apoptosis
      induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma
      T24 and 5637 cells. CONCLUSIONS: Our data suggest that lincRNA TUG1 is emerging
      as a novel player in the disease state of bladder urothelial carcinoma. TUG1 may
      have potential roles as a biomarker and/or a therapeutic target in bladder
      urothelial carcinoma.

PMID- 22961207
TI  - Clinico-epigenetic combination including quantitative methylation value of DKK3
      augments survival prediction of the patient with cervical cancer.
AB  - PURPOSE: DKK3 is a target of methylation in various cancers and has been studied
      by a non-quantitative method. We assessed the quantitative methylation levels of
      DKK3 in cervical carcinoma, determined the potential clinical correlations, and
      tested whether the combination of clinical and epigenetic factors augmented the
      prediction power of prognosis. METHODS: Sixty-two patients with cervical squamous
      cell carcinoma were included in this study. Quantitative methylation levels were
      evaluated by pyrosequencing. Clinical and pathologic findings were obtained from
      medical records. Survival data were analyzed using Kaplan-Meier estimates and
      compared with the log-rank test. The best clinico-epigenetic combinations were
      found using the Cox proportional hazard model. RESULTS: Four of five CpG
      positions of DKK3 were strongly methylated in cervical carcinoma compared to
      normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were
      stronger in patients with higher serum levels of the SCC tumor marker and/or
      larger tumors (p = 0.01). The patients with a methylation level >=26.3 % at
      position 1 had a lower survival rate than the patients with methylation levels at
      position 1 that were <26.3 % (p = 0.03). The combination of methylation level of
      position 1, position 3, age, parametrial invasion, and lymphovascular space
      invasion (LVSI) have a significant correlation with survival (p = 0.0006).
      Recurrence was significantly related to the combination of methylation level of
      position 2, position 3, age, parametrium, and LVSI (p = 0.0041). CONCLUSIONS:
      DKK3 methylation is unfavorable to prognosis. This study defined a threshold
      level of methylation associated with recurrence-free survival and, furthermore,
      identified novel clinico-epigenetic combinations predicting disease survival or
      recurrence.

PMID- 22961208
TI  - Biological characteristics of interval cancers: a role for biomarkers in the
      breast cancer screening.
AB  - INTRODUCTION: In a population-based screening program, a percentage of tumors
      remain undetected; these tumors comprise a heterogeneous group, and they are more
      likely to have adverse prognostic features. The aim of this study was to identify
      differences in biological characteristics of screen-detected versus interval
      breast cancers in a population-based screening program according to molecular
      subtypes. MATERIALS AND METHODS: We analyzed the population-based data from a
      long-running screening program in the area of Florence. Data on screening history
      and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2
      expression were retrieved. Subtypes of breast cancer were defined on the
      expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki67 <14 %,
      luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 >=14 %, luminal B (HER2
      positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive
      if ER/PR- and HER2+. Association between molecular subtypes and mode of detection
      will be evaluated by a logistic regression model adjusted for the potential
      confounding variables. RESULTS: Information about biomarkers was known for 277
      cases, 211 screening-detected and 66 interval cancers. Among interval cases, the
      triple-negative cancers were more represented than luminal A (OR = 3.52; CI,
      1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR =
      1.57; p = 0.4709). CONCLUSION: Although made on a small number of cases, our
      results suggest a difference in distribution of molecular subtypes according to
      mode detection, confirming the results of earlier studies.

PMID- 22961209
TI  - Electrochemistry of Q-graphene.
AB  - A newly synthesised type of graphene, Q-Graphene, has been physically and
      electrochemically characterised with Scanning and Transmission Electron
      Microscopy (SEM, TEM), X-ray Photoelectron Spectroscopy (XPS) and Cyclic
      Voltammetry (CV). Interpretation of SEM, TEM and XPS data reveal the material to
      consist of hollow carbon nanospheres of multi-layer graphene (viz. graphite),
      which exhibit a total oxygen content of ca. 36.0% (atomic weight via XPS). In
      addition to the carbon structures present, spherical magnesium oxide particles of
      <=50 nm in diameter are abundantly present in the sample (ca. 16.2%).
      Interestingly, although the TEM/SEM images show macroporous carbon structures,
      Raman spectroscopy shows peaks typically characteristic of graphene, which
      suggests the material is highly heterogeneous and consists of many types of
      carbon allotropes. Q-Graphene is electrochemically characterised using both inner
      sphere and outer-sphere electrochemical redox probes, namely potassium
      ferrocyanide(II), hexaammine-ruthenium(III) chloride and hexachloroiridate(III),
      in addition to the biologically relevant and electroactive analytes,
      norepinephrine, beta-nicotinamide adenine dinucleotide (NADH) and l-ascorbic
      acid. The electrochemical response of Q-Graphene is benchmarked against edge
      plane- and basal plane-pyrolytic graphite (EPPG and BPPG respectively), pristine
      graphene and graphite alternatives. Q-Graphene is found to exhibit fast electron
      transfer kinetics, likely due to its high proportion of folded edges and surface
      defects, exhibiting a response similar to that of EPPG - which exhibits fast
      electron transfer rates due to the high proportion of edge plane sites it
      possesses. Furthermore, we demonstrate that the specific oxygen content plays a
      pivotal role in dictating the observed electrochemical response, which is analyte
      dependant. Consequently there is potential for this new member of the graphene
      family to be beneficially utilised in various electrochemical applications.

PMID- 22961210
TI  - Study of protoporphyrin IX elimination by body excreta: a new noninvasive cancer
      diagnostic method?
AB  - This paper describes the elimination of porphyrins by feces. It was demonstrated
      that porphyrin accumulates substantially more in tumors than in normal tissues,
      and consequently more PPIX reaches the blood of patients and animals with tumors,
      and then, it needs to be eliminated. The fluorescence of feces revealed that
      there are large amounts of PPIX in the excreta of animals with cancer comparing
      with healthy animals. The autofluorescence of feces porphyrin extracted with
      acetone was analyzed using fluorescence spectroscopy of animals inoculated with
      DU145 cells into the prostate and healthy animals to monitor the PPIX
      concentration. Emission spectra were obtained by exciting the samples at 405 nm.
      Significant differences were observed in autofluorescence intensities measured in
      the 575-725 nm spectral regions for the studied groups. The results showed a
      noninvasive, simple, rapid and sensitive method to detect cancer by feces
      analysis.

PMID- 22961211
TI  - [Haemophilia and cartilage--the role of movement].
AB  - It is not the blood alone! Increased loading destroys cartilage and leads to
      arthrosis. Reduced mechanical stimulation leads to reduced cartilage nutrition
      and to cartilage degeneration, which leads to arthrosis. We know about the
      existence of functional disturbances that occur in early childhood before any
      structural changes are diagnosed. This is typical for haemophilia. Those
      disturbances and the way movement is disturbed has a strong influence on the
      loading of cartilage. This involves acceleration peaks, disturbed load
      distribution with reduction of contact area and a change of vector direction,
      which leads to increased cartilage loading. The disturbed function can be
      analysed very early with motion analysis. Easy physiotherapeutical interventions
      are able to optimise function again. On top of that we have a loss of muscle
      contraction pattern. Around the knee joint it is the weakening of the vastus
      medialis and the shortening of the knee flexors. The ankle joint suffers from a
      weakening of the tibialis anterior and a shortening of the calf muscles. During
      progression of the disease there will be a shortening of the weakened muscle and
      a weakening of the shortened muscle as well. Kinetic superficial EMG is able to
      quantify the status of the muscles and enables us to prescribe an individual
      therapy. Subclinical influences like microbleeds, in the beginning silent
      synovitis, later chronic synovitis, silent symptoms and overprotection are the
      cause of the functional overloading of the cartilage in patient with haemophilia.
      Silent symptoms can be discovered by clinical examination. Again this leads to
      the opportunity of a symptomatic therapeutic approach. All those facts could be
      the reason why there is an increasing incidence of haemarthrophathy of the ankle
      joint, even in patients with mild haemophilia in spite of adequate factor
      substitution.

PMID- 22961213
TI  - Chronic cerebrospinal venous insufficiency is not more prevalent in patients with
      mild multiple sclerosis: a sonographer-blinded, case-control ultrasound study.
AB  - OBJECTIVES: We designed a prospective case-control study of patients with
      clinically isolated syndrome (CIS) and Relapsing-Remitting Multiple Sclerosis
      (RRMS) with an Expanded Disability Status Score (EDSS) of <=2, compared with age
      and-sex-matched healthy controls, to test the hypothesis that chronic
      cerebrospinal venous insufficiency (CCSVI) is more prevalent in patients with CIS
      or mild MS. METHODS: All subjects were examined using a Siemens Antares duplex
      ultrasound machine. The internal jugular, vertebral and intracranial veins were
      studied in subjects in both supine and sitting postures. The sonographer was
      blind to the subject's clinical status. Measures included the criteria proposed
      by Zamboni and volume flow. Presence of CCSVI was defined as >=2 Zamboni
      criteria. RESULTS: Seventy patient-control pairs were recruited, with 11 males
      and 59 females in each group. Only one subject, a control, satisfied the Zamboni
      definition of CCSVI; however, 19 patients and 13 controls had abnormalities as
      defined by Zamboni, the difference largely caused by a higher prevalence in
      patients of internal jugular vein (IJV) stenosis, defined as a cross-sectional
      area <=0.3cm(2). This difference disappeared with a more rigorous stenosis
      definition. Further analysis revealed there was IJV valve variation in seven
      patients and one control. CONCLUSIONS: Our findings indicate that CCSVI, as
      defined by the Zamboni ultrasound criteria, is not present in CIS and mild RRMS
      (EDSS <=2), providing further evidence that CCSVI does not have a causal role in
      MS; however, we found an apparent increase in IJV variation in patients with CIS
      or mild MS that would warrant further investigation.

PMID- 22961212
TI  - Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with
      different metastatic potential.
AB  - We quantified mechanical properties of cancer cells differing in metastatic
      potential. These cells included normal and H-ras-transformed NIH3T3 fibroblast
      cells, normal and oncoprotein-overexpressing MCF10A breast cancer cells, and
      weakly and strongly metastatic cancer cell line pairs originating from human
      cancers of the skin (A375P and A375SM cells), kidney (SN12C and SN12PM6 cells),
      prostate (PC3M and PC3MLN4 cells), and bladder (253J and 253JB5 cells). Using
      magnetic twisting cytometry, cytoskeletal stiffness (g') and internal friction
      (g") were measured over a wide frequency range. The dependencies of g' and g"
      upon frequency were used to determine the power law exponent x which is a direct
      measure of cytoskeletal fluidity and quantifies where the cytoskeleton resides
      along the spectrum of solid-like (x = 1) to fluid-like (x = 2) states.
      Cytoskeletal fluidity x increased following transformation by H-ras oncogene
      expression in NIH3T3 cells, overexpression of ErbB2 and 14-3-3-zeta in MCF10A
      cells, and implantation and growth of PC3M and 253J cells in the prostate and
      bladder, respectively. Each of these perturbations that had previously been shown
      to enhance cancer cell motility and invasion are shown here to shift the
      cytoskeleton towards a more fluid-like state. In contrast, strongly metastatic
      A375SM and SN12PM6 cells that disseminate by lodging in the microcirculation of
      peripheral organs had smaller x than did their weakly metastatic cell line pairs
      A375P and SN12C, respectively. Thus, enhanced hematological dissemination was
      associated with decreased x and a shift towards a more solid-like cytoskeleton.
      Taken together, these results are consistent with the notion that adaptations
      known to enhance metastatic ability in cancer cell lines define a spectrum of
      fluid-like versus solid-like states, and the position of the cancer cell within
      this spectrum may be a determinant of cancer progression.

PMID- 22961214
TI  - Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis:
      associations with disease course and progression.
AB  - BACKGROUND: The use of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF)
      parameters are established in the diagnosis of MS, but poorly as markers of
      disease. OBJECTIVE: To investigate the role of OCBs in disease course and
      progression. METHODS: CSF data for 1120 patients with MS were analyzed for
      associations between OCBs and CSF parameters and clinical data (disease course
      [relapsing-onset MS (ROMS) vs primary-progressive MS (PPMS)]), disability
      progression (proportion reaching Expanded Disability Status Scale 6 within 10
      years of onset and progression index) and ethnicity. RESULTS: Of patients with
      MS, 72.5% had detectable OCBs. For patients with detectable OCBs, 84.6% had ROMS
      and 15.4% PPMS versus 89.7% and 10.3%, respectively for those without detectable
      OCBs (p=0.04). Total CSF IgG and protein levels were higher in PPMS compared with
      ROMS (p<0.001). Disease progression appeared independent of OCB status. Patients
      with CSF (vs without) data were more likely to be male, older at onset, have PPMS
      and lack optic neuropathy at onset (p<0.001). CONCLUSIONS: OCB positivity and
      elevated total CSF IgG and protein were moderately associated with a PPMS disease
      course, but not disease progression. Patients with atypical clinical
      presentations were more likely to have had CSF work-up, suggesting a testing
      bias.

PMID- 22961215
TI  - The effect of EMLA cream on minimizing pain during venipuncture in premature
      infants.
AB  - BACKGROUND: Painful procedures for premature infants in neonatal intensive care
      units remain inevitable. The goal of this study is to evaluate the effect of an
      eutectic mixture of local anesthetic (EMLA) cream for minimizing pain in
      premature infants during venipuncture in neonatal intensive care units. METHODS:
      This study enrolled 32 premature infants. A repeated-measures design was used.
      The scores of the 'Neonatal Pain, Agitation and Sedation Scale' (N-PASS) of each
      enrolled preterm infant were measured before, during and 10 min after
      venipuncture without and with EMLA cream use. Paired t-tests were used to compare
      the difference of N-PASS scores without and with EMLA cream use. RESULTS: Paired
      t-tests revealed a significant decrease in N-PASS scores during venipuncture in
      infants with EMLA cream. There was no significant change of N-PASS scores before,
      during and 10 min after venipuncture with EMLA cream by analysis of repeated
      analysis of variance. CONCLUSION: EMLA cream for minimizing pain during
      venipuncture could be recommended for premature infants.

PMID- 22961216
TI  - Injection site reaction after subcutaneous administration of bortezomib in
      Japanese patients with multiple myeloma.

PMID- 22961217
TI  - Mercury speciation and total organic carbon in marine sediments along the
      Mediterranean coast of Israel.
AB  - Along the Israeli Mediterranean Coast, three areas are considered "hot spots" of
      mercury (Hg) pollution: (1) Northern Haifa Bay (NHB), (2) the lower Qishon River
      at the southern part of Haifa Bay, and (3) a marine outfall of activated sewage
      sludge at the southern coast off Palmachim (sewage-sludge disposal site [SDS]).
      Even though the total Hg (HgT) concentrations in the sediments at the three areas
      are of the same order of magnitude (250-500 MUg kg(-1)), Hg was shown to
      bioaccumulate in fish and benthic fauna from Haifa Bay but not in benthic fauna
      or in commercial fish caught along the southern Mediterranean Coast of Israel
      near the SDS outfall. The primary goal of this study was to measure the
      concentrations of Hg species (HgT, methyl-Hg [MeHg], and Hg in different
      biogeochemical fractions)-in conjunction with organic carbon-in sediments of NHB
      and the lower Qishon River to assess its impact on Hg transitions among the
      species as characterized by different bioavailability and bioaccessibility. HgT
      concentrations in NHB and the Qishon River ranged from 249 to 347 and 165 to 667
      MUg kg(-1), respectively. MeHg was significantly higher in the Qishon River (6.3
      34.0 MUg kg(-1)) than in NHB (0.22-0.70 MUg kg(-1)) as were total organic carbon
      (TOC) concentrations (average 2.5 vs. 0.13 %). The relative Hg distribution in
      the biogeochemical fractions in NHB was 2.3 % in the most bioaccessible fractions
      (F1 + F2), 55 % in the organo-chelated species fraction (F3), 42 % in the strong
      complexed species fraction (F4), and 0.7 % in the mercuric-sulfide fraction (F5).
      In the Qishon River, the bioavailable F1 + F2 and F3 fractions were lower than in
      NHB (<0.01 and 23 %, respectively) and the more refractory F4 and F5 fractions
      higher (73 and 3.3 %, respectively). The fractionation of Hg in Qishon River
      sediments was similar to the distribution found in polluted stations at the SDS.
      TOC and MeHg were positively and negatively correlated, respectively, in Qishon
      River and NHB sediments. Methylation depended on TOC availability when its
      concentration was in the range of 2-4 wt%. It is possible that TOC in the
      sediment controlled Hg speciation: Hg in F3 decreased and in F4 increased with
      increasing TOC concentrations. In contrast, MeHg/HgT was significantly positively
      correlated with TOC and Hg in the stable F4 fraction and negatively correlated
      with Hg in the F3 fraction. It was therefore assumed that higher TOC
      concentrations enhanced microbial activity and decomposition of organic matter.
      Hg was released from the F3 fraction and was either transferred to the F4
      fraction or made available for methylation processes.

PMID- 22961218
TI  - Effects of the veterinary pharmaceutical salinomycin and its formulation on the
      plant Brassica rapa.
AB  - Veterinary pharmaceuticals are emerging contaminants found throughout the
      environment, and their presence and effects are a matter of concern. The purpose
      of this study was to compare the phytotoxicity of salinomycin (pure compound = 96
      %) and Sacox 120 (formulated product = 120 g salinomycin/kg) to the plant species
      Brassica rapa as well as to investigate salinomycin persistence in soil.
      Calculated EC/IC(50) values for salinomycin and Sacox 120 were 1.10 and 2.88 and
      2.19 and 18.03 mg/kg, respectively, based on salinomycin concentration. For
      exposure of B. rapa to salinomycin, significant adverse effects were observed for
      growth end points at the greater concentrations. For the reproduction end point
      (i.e., number of buds), as well as root length and wet mass, significant
      differences were observed at the lower concentrations (stimulating growth) and
      adverse effects at the greater concentrations. This study confirmed that the
      toxic effects of Sacox 120 are attributable to the active ingredient salinomycin.
      Liquid chromatography-electrospray ionization-mass spectrometry analyses
      confirmed that exposure concentrations of salinomycin were 90 and 83 % of the
      nominal concentrations, respectively, in the soils amended with either pure or
      formulated product. At the end of the experiment, after 14 days, salinomycin
      concentrations for both tests (salinomycin and Sacox 120) decreased to 6.2 and
      5.8 % of the nominal exposure concentrations, respectively. Detected salinomycin
      concentrations in plant shoots ranged from 3.47 to 41.0 ng/g dry shoot. This
      study shows the importance of using plants as tools to evaluate environmental
      risk and as a bridge to relate environment and human health risks.

PMID- 22961219
TI  - Luminance contours can gate afterimage colors and "real" colors.
AB  - It has long been known that colored images may elicit afterimages in
      complementary colors. We have already shown (Van Lier, Vergeer, & Anstis, 2009)
      that one and the same adapting image may result in different afterimage colors,
      depending on the test contours presented after the colored image. The color of
      the afterimage depends on two adapting colors, those both inside and outside the
      test. Here, we further explore this phenomenon and show that the color-contour
      interactions shown for afterimage colors also occur for "real" colors. We argue
      that similar mechanisms apply for both types of stimulation.

PMID- 22961220
TI  - Surround facilitation for rapid motion perception.
AB  - Because we live in a dynamic environment with moving eyes and body, our retinas
      are often stimulated by new scenes that appear suddenly and are only briefly
      available. How the visual system successfully extracts information from such
      challenging stimulation is not yet understood. For some stimuli, like photos of
      natural scenes, we are accurate in detecting objects like animals or faces even
      when the stimulus is presented for a short time. For other stimuli, like noisy
      motion, previous studies have shown accurate perception only when the stimulus is
      presented for a long time--often longer than the typical available time of a
      stimulus in natural viewing. Here we show, however, that a transient surround can
      accelerate the perception of motion. We found that for briefly displayed random
      dots, the signal necessary to detect motion is reduced from 19% to 8% when a task
      irrelevant surround is presented in synchrony with the random-dots, while no
      improvement occurs when the surround is sustainedly presented, or when it is
      transiently, but asynchronously, presented. We also found that motion sensitivity
      increases steadily with duration when no surround is presented, confirming
      previous findings, but duration has little effect on sensitivity when a
      synchronous surround is presented. Further results indicate that the facilitation
      by a synchronous surround is related to relative-motion processing. Our findings
      suggest that spatial interactions might assist rapid perception of motion.

PMID- 22961221
TI  - Seeing the last part of a hitting movement is enough to adapt to a temporal
      delay.
AB  - Being able to see the object that you are aiming for is evidently useful for
      guiding the hand to a moving object. We examined to what extent seeing the moving
      hand also influences performance. Subjects tried to intercept moving targets
      while either instantaneous or delayed feedback about the moving hand was provided
      at certain times. After each attempt, subjects had to indicate whether they
      thought they had hit the target, had passed ahead of it, or had passed behind it.
      Providing visual feedback early in the movement enabled subjects to use visual
      information about the moving hand to correct their movements. Providing visual
      feedback when the moving hand passed the target helped them judge how they had
      performed. Performance was almost as good when visual feedback about the moving
      hand was provided only when the hand was passing the target as when it was
      provided throughout the movement. We conclude that seeing the temporal
      relationship between the hand and the target as the hand crosses the target's
      path is instrumental for adapting to a temporal delay.

PMID- 22961222
TI  - Equivalent cardioprotection induced by ischemic and hypoxic preconditioning.
AB  - OBJECTIVE: We aimed to compare cardioprotection induced by various hypoxic
      preconditioning (HPC) and ischemic preconditioning (IPC) protocols. METHODS:
      Isolated rat hearts were randomly divided into 7 groups (n = 7 per group) and
      received 3 or 5 cycles of 3-minute ischemia or hypoxia followed by 3-minute
      reperfusion (IPC33 or HPC33 or IPC53 or HPC53 group), 3 cycles of 5-minute
      ischemia or hypoxia followed by 5-minute reperfusion (IPC35 group or HPC35
      group), or 30-minute perfusion (ischemic/reperfusion group), respectively. Then
      all the hearts were subjected to 50-minute ischemia and 120-minute reperfusion.
      Cardiac function, infarct size, and coronary flow rate (CFR) were evaluated.
      RESULTS: Recovery of cardiac function and CFR in IPC35, HPC35, and HPC53 groups
      was significantly improved as compared with I/R group (p < 0.01). There were no
      significant differences in cardiac function parameters between IPC35 and HPC35
      groups. Consistently, infarct size was significantly reduced in IPC35, HPC35, and
      HPC53 groups compared with ischemic/reperfusion group. CONCLUSION: Multiple-cycle
      short duration HPC exerted cardioprotection, which was as powerful as that of
      IPC.

PMID- 22961223
TI  - Acute mastoiditis: the role of imaging for identifying intracranial
      complications.
AB  - OBJECTIVES/HYPOTHESIS: Brain CT is performed in patients presenting with acute
      mastoiditis (AM) to identify intracranial complications (ICC). Recently, however,
      the need for CT scans in such patients has been questioned owing to concerns
      regarding long-term effects of brain irradiation, with some clinicians claiming
      that the decision to scan should be based on a patient's clinical presentation.
      This study was aimed at characterizing the typical clinical presentation of
      patients who already have ICCs when diagnosed with AM, and to compare it to that
      of AM patients presenting without ICCs. STUDY DESIGN: Prospective case series.
      METHODS: All patients hospitalized with AM between July 1997 and December 2009 in
      an otologic tertiary referral center were divided into those with and those
      without ICCs on presentation. Prereferral clinical characteristics and the signs,
      symptoms, and inflammatory indexes at presentation were compared between the two
      groups. RESULTS: Of 71 patients presenting with AM, 10 had at least one ICC
      (sigmoid sinus thrombosis [nine patients], perisinus empyema [five patients],
      subdural abscess [one patient], and epidural abscess [one patient]). Patients
      with and without ICCs did not differ regarding most clinical characteristics or
      presenting signs and symptoms. None presented with neurological signs or cranial
      nerve deficits. CONCLUSIONS: It is not possible to define an evidence-based index
      of suspicion for ICCs in patients with AM. Diagnostic imaging at presentation
      accordingly remains mandatory.

PMID- 22961224
TI  - Antimicrobial stewardship as part of the infection prevention effort.
AB  - Antimicrobial stewardship programs (ASPs) optimize antimicrobial use to decrease
      the incidence of infection with multidrug-resistant organisms (MDRO) and the
      emergence of drug resistance, to improve patient outcomes and safety, and to
      decrease hospital costs. ASPs achieve these goals through several types of
      interventions that can occur before or after the antimicrobial has been
      prescribed; interventions can also be "active" or "passive." We believe that
      active post-prescription interventions such as post-prescription audit and
      feedback have the most supportive evidence and most promise. Stewardship
      activities must be integrated into already established efforts for infection
      prevention. We believe it is critical that antimicrobial stewardship, infection
      control, pharmacy, information technology, and clinical microbiology work
      collaboratively in order to decrease the incidence of infection due to MDRO.

PMID- 22961225
TI  - Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the
      skeletal muscle of healthy young men.
AB  - AIMS/HYPOTHESIS: Energy-dense diets that are high in fat are associated with a
      risk of metabolic diseases. The underlying molecular mechanisms could involve
      epigenetics, as recent data show altered DNA methylation of putative type 2
      diabetes candidate genes in response to high-fat diets. We examined the effect of
      a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation
      patterns in human skeletal muscle. METHODS: Skeletal muscle biopsies were
      obtained from 21 healthy young men after ingestion of a short-term HFO diet and a
      control diet, in a randomised crossover setting. DNA methylation was measured in
      27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate
      gene expression was determined by quantitative real-time PCR. RESULTS: HFO
      introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a
      maximum methylation change of 13.0 percentage points. The HFO-induced methylation
      changes were only partly and non-significantly reversed after 6-8 weeks.
      Alterations in DNA methylation levels primarily affected genes involved in
      inflammation, the reproductive system and cancer. Few gene expression changes
      were observed and these had poor correlation to DNA methylation.
      CONCLUSIONS/INTERPRETATION: The genome-wide DNA methylation changes induced by
      the short-term HFO diet could have implications for our understanding of
      transient epigenetic regulation in humans and its contribution to the development
      of metabolic diseases. The slow reversibility suggests a methylation build-up
      with HFO, which over time may influence gene expression levels.

PMID- 22961227
TI  - Synthesis and supramolecular assembly of the bifunctional borinic acid [1,2
      fcB(OH)]2.
AB  - Treatment of the chloro-substituted diboradiferrocene derivative 1 with
      Me(3)SiOMe and subsequent hydrolysis resulted in formation of the novel
      organometallic bis(borinic acid) derivative 3. The assembly of 3 into
      supramolecular structures via hydrogen bonding and reversible covalent boron
      oxygen bond formation was explored. Upon crystallization from acetone or THF one
      dimensional chains form in which molecules of 3 alternately serve as hydrogen
      bond donors and acceptors. The additional OH hydrogens that are not involved in
      hydrogen bonding within the polymeric chains undergo hydrogen bonding to the
      solvent molecules. Removal of the solvent was achieved at moderate temperature
      under high vacuum. While the polymeric chains remain intact, in the absence of
      the solvent as a hydrogen bond acceptor, short contacts to the Cp rings of
      neighboring polymer strands lead to a network-like structure. At higher
      temperatures, further dehydration occurs with formation of B-O-B linkages as
      confirmed by MALDI-TOF mass spectrometry. Oligomers with up to 15 repeating units
      (30 ferrocenes) were detected.

PMID- 22961226
TI  - Chromosome substitution strains: gene discovery, functional analysis, and systems
      studies.
AB  - Laboratory mice are valuable in biomedical research in part because of the
      extraordinary diversity of genetic resources that are available for studies of
      complex genetic traits and as models for human biology and disease. Chromosome
      substitution strains (CSSs) are important in this resource portfolio because of
      their demonstrated use for gene discovery, genetic and epigenetic studies,
      functional characterizations, and systems analysis. CSSs are made by replacing a
      single chromosome in a host strain with the corresponding chromosome from a donor
      strain. A complete CSS panel involves a total of 22 engineered inbred strains,
      one for each of the 19 autosomes, one each for the X and Y chromosomes, and one
      for mitochondria. A genome survey simply involves comparing each phenotype for
      each of the CSSs with the phenotypes of the host strain. The CSS panels that are
      available for laboratory mice have been used to dissect a remarkable variety of
      phenotypes and to characterize an impressive array of disease models. These
      surveys have revealed considerable phenotypic diversity even among closely
      related progenitor strains, evidence for strong epistasis and for heritable
      epigenetic changes. Perhaps most importantly, and presumably because of their
      unique genetic constitution, CSSs, and congenic strains derived from them, the
      genetic variants underlying quantitative trait loci (QTLs) are readily identified
      and functionally characterized. Together these studies show that CSSs are
      important resource for laboratory mice.

PMID- 22961228
TI  - GSK3beta signaling is involved in ultraviolet B-induced activation of autophagy
      in epidermal cells.
AB  - Ultraviolet B (UVB) exposure causes damage to skin and represents the primary
      etiological agent for skin cancer formation. UVB induces DNA damage and apoptosis
      in epidermal cells. In this study, we demonstrated that UVB activated autophagy
      in JB6 epidermal cells, which was evident by the formation of LC3 puncta, the
      induction of LC3 lipidation, the increase in beclin 1 expression, and the
      decrease in the levels of p62. Autophagy appeared to be a protective response to
      UVB-induced damage because inhibition of autophagy exacerbated UVB-induced cell
      death, and stimulation of autophagy offered protection. Furthermore, we
      demonstrated that glycogen synthase kinase 3beta (GSK3beta) was involved in UVB
      induced autophagy. UVB inhibited GSK3beta activation by simultaneously enhancing
      phosphorylation at Ser9 and suppressing Tyr216 phosphorylation. GSK3beta
      negatively regulated autophagy; overexpression of wild-type or S9A (constitutive
      active) GSK3beta mutant inhibited UVB-mediated autophagy, while overexpression of
      a dominant-negative K85R mutant enhanced UVB-mediated autophagy. Inhibition of
      GSK3beta also offered protection against UVB-mediated damage. UVB activated AMP
      activated protein kinase (AMPK), an important regulator of autophagy through the
      inhibition of GSK3beta. Taken together, our results suggest that UVB-stimulated
      autophagy is a protective response for epidermal cells and is mediated by the
      GSK3beta/AMPK pathway.

PMID- 22961229
TI  - Examining the determinants of drug launch delay in pre-TRIPS India.
AB  - The dynamics of drug launch has been an under-researched area, especially in the
      context of developing countries, which have diverse disease profiles and weaker
      forms of regulation compared to developed countries. A limited set of studies,
      undertaken in recent years, on the diffusion of new drugs in developing countries
      indeed conjectures the importance of these factors in shaping drug launch
      dynamics. Taking a survival analysis approach, we investigate the delay of new
      drug launch in India for drugs launched in the German market during 1990-2004,
      when, due to weak intellectual property rights (IPR), not only the innovators but
      also domestic firms could launch new drug molecules in the country. The paper
      makes an attempt to distinguish between the commercial success of a new drug and
      its innovativeness. We find little association between these two characteristics
      of a drug. Also, the influence of global commercial success in shortening delay
      is much stronger than that of innovativeness. The study also finds interesting
      results for the threat of imposition of a strong IPR system, market structure and
      first mover advantages. Policy implications are discussed briefly. 

PMID- 22961231
TI  - Could co-payments on drugs help to make EU health care systems less open to
      political influence?

PMID- 22961230
TI  - The cost-effectiveness of smoking cessation support delivered by mobile phone
      text messaging: Txt2stop.
AB  - BACKGROUND: The txt2stop trial has shown that mobile-phone-based smoking
      cessation support doubles biochemically validated quitting at 6 months. This
      study examines the cost-effectiveness of smoking cessation support delivered by
      mobile phone text messaging. METHODS: The lifetime incremental costs and benefits
      of adding text-based support to current practice are estimated from a UK NHS
      perspective using a Markov model. The cost-effectiveness was measured in terms of
      cost per quitter, cost per life year gained and cost per QALY gained. As in
      previous studies, smokers are assumed to face a higher risk of experiencing the
      following five diseases: lung cancer, stroke, myocardial infarction, chronic
      obstructive pulmonary disease, and coronary heart disease (i.e. the main fatal or
      disabling, but by no means the only, adverse effects of prolonged smoking). The
      treatment costs and health state values associated with these diseases were
      identified from the literature. The analysis was based on the age and gender
      distribution observed in the txt2stop trial. Effectiveness and cost parameters
      were varied in deterministic sensitivity analyses, and a probabilistic
      sensitivity analysis was also performed. FINDINGS: The cost of text-based support
      per 1,000 enrolled smokers is L16,120, which, given an estimated 58 additional
      quitters at 6 months, equates to L278 per quitter. However, when the future NHS
      costs saved (as a result of reduced smoking) are included, text-based support
      would be cost saving. It is estimated that 18 LYs are gained per 1,000 smokers
      (0.3 LYs per quitter) receiving text-based support, and 29 QALYs are gained (0.5
      QALYs per quitter). The deterministic sensitivity analysis indicated that changes
      in individual model parameters did not alter the conclusion that this is a cost
      effective intervention. Similarly, the probabilistic sensitivity analysis
      indicated a >90 % chance that the intervention will be cost saving.
      INTERPRETATION: This study shows that under a wide variety of conditions,
      personalised smoking cessation advice and support by mobile phone message is both
      beneficial for health and cost saving to a health system.

PMID- 22961232
TI  - What determines health: a causal analysis using county level data.
AB  - This article revisits the long-standing issue of the determinants of health
      outcomes. We make two contributions to the literature. First, we use a large and
      comprehensive US county level health data set that has only recently become
      available. This data set includes five measures of health outcomes and 24 health
      risk factors in the categories of health behaviors, clinical care, social and
      economic factors, and physical environment. Second, to distinguish causality from
      correlation, we implement an emerging data-driven method to study the causal
      factors of health outcomes. Among all included potential health risk factors, we
      identify adult smoking, obesity, motor vehicle crash death rate, the percent of
      children in poverty, and violent crime rate to be major causal factors of
      premature mortality. Adult smoking, preventable hospital stays, college or higher
      education, employment, children in poverty, and adequacy of social support
      determine health-related quality of life. Finally, the Chlamydia rate, community
      safety, and liquor store density are three important factors causally related to
      low birth weight. Policy implications of these findings are discussed. 

PMID- 22961233
TI  - A study on seroprevalence of caprine brucellosis under three livestock production
      systems in southern and central Ethiopia.
AB  - Caprine brucellosis in Ethiopia is less commonly reported with limited
      information on the disease status in the country. The objective of this study was
      therefore to highlight the status of goat brucellosis in three distinctly
      different livestock production systems of southern and central Ethiopia. A total
      3,315 goats of different age and sex, living with other animals in variable flock
      size, were sampled from 448 flocks raised in sedentary, pastoral and agro
      pastoral production systems. Goats were bled aseptically and sera were collected
      for serial testing using Rose Bengal Plate Test as screening test and
      subsequently complement fixation test as confirmatory test. Questionnaire and
      laboratory data were analysed for descriptive, univariable and multivariable
      logistic regression analysis both at individual and flock level (STATA 11). The
      study revealed an overall animal level seroprevalence of 1.9 % (95 % CI 1.5,
      2.4). In sedentary production system, the observed seroprevalence was 0.6 % (95 %
      CI 0.2, 0.9) while 1.9 % (95 % CI 1.1, 2.7) and 7.6 % (95 % CI 5.1, 10.1) were
      the proportion of seroreactors for agro-pastoral and pastoral production systems,
      respectively. The observed prevalence difference between the three production
      systems was statistically significant (P < 0.05). At the flock level analysis,
      11.2 % (95 % CI 8.2, 14.1) of the flocks sampled had at least one seropositive
      goat among themselves. Like individual level analysis, the highest prevalence of
      32.5 % (95 % CI 21.9, 43.0) was recorded for pastoral production system, followed
      by agro-pastoral, 13.0 % (95 % CI 7.0, 19.0) and sedentary production system, 3.6
      % (95% CI 1.3, 6.0). Accordingly, the odds of Brucella seropositivity were higher
      (OR = 12.8) in pastoral followed by agro-pastoral (OR = 4.0) in relation to
      sedentary production system. Large numbers of seroreactors were observed in adult
      age living in larger flocks with other livestock species. However, no difference
      was noted between male and female goats. Finally, the need for nationwide survey
      and subsequent designing and implementation of appropriate control measure is
      suggested.

PMID- 22961234
TI  - The effect of the contents of exomphalos and nuchal translucency at 11-14 weeks
      on the likelihood of associated chromosomal abnormality.
AB  - OBJECTIVES: Previous publications suggest that exomphalos containing the liver as
      less likely to be associated with aneuploidy. The objective of the study was to
      explore the influence of exomphalos contents and nuchal translucency (NT) on the
      likelihood of aneuploidy. METHODS: A retrospective search was conducted to
      identify all cases of exomphalos from the databases of two fetal medicine units
      seen from September 2000 to March 2011. RESULTS: A total of 95 fetuses with
      exomphalos were selected. NT was normal in 42 fetuses (44.2%). The exomphalos
      content was bowel alone in 68 (71.6%). The effect of exomphalos content and NT on
      likelihood of aneuploidy was explored using logistic regression. It showed no
      significant contribution of exomphalos content on the likelihood of aneuploidy
      (adjusted odds ratio: 1.44, 95% CI: 0.538 to 3.84). CONCLUSIONS: When the
      diagnosis is made in the first trimester, the risk of aneuploidy is no different
      when the sac contains only bowel as compared with when it contains the liver.
      Increase in the NT is 4-5 times as likely with an abnormal karyotype as with
      normal NT. Detection of exomphalos in the first trimester warrants an offer of
      chromosomal assessment regardless of sac contents or NT.

PMID- 22961235
TI  - The Strongylidae belonging to Strongylus genus in horses from southeastern
      Poland.
AB  - Postmortem parasitic examinations of the large intestines of 725 slaughtered
      horses from individual farmers in southeastern Poland were carried out. The
      examinations were carried out monthly since February 2006 until January 2007
      (except for August 2007 because of a technological stoppage in the
      slaughterhouse). The examinations included the intensiveness and extensiveness of
      the infestation of the Strongylidae belonging to the Strongylus genus. The
      Strongylidae were found in 26.5% of the examined horses. Strongylus vulgaris was
      the most dominant nematode and had a 22.8% prevalence, Strongylus edentatus was
      carried by 18.3% of the horses. Strongylus equinus was identified only in 1.7% of
      the examined horses. Our findings revealed that combined infestation of S.
      vulgaris and S. edentatus occurred in 100 (52.1%) of the 725 horses infected by
      the Strongylidae. The present results indicate that the lowest prevalence of
      strongyle species except for S. equinus was found in January, February, and
      March. However, it is difficult to draw a conclusion because of an extremely low
      extensiveness of infestation. The results indicate that the prevalence of the
      Strongylidae in horses from southeastern Poland is limited.

PMID- 22961236
TI  - Genetic diversity of caprine Blastocystis from Peninsular Malaysia.
AB  - Blastocystis sp. is a common intestinal parasite found in humans and animals. The
      possibility of zoonotic transmission to humans from livestock especially goats
      led us to investigate the genetic diversity of caprine Blastocystis sp. obtained
      from five different farms in Peninsular Malaysia. Moreover, there is a lack of
      information on the prevalence as well as genetic diversity of Blastocystis sp. in
      goat worldwide. Results showed that 73/236 (30.9 %) of the goats were found to be
      positive for Blastocystis infection. The most predominant Blastocystis sp.
      subtype was ST1 (60.3 %) followed by ST7 (41.1 %), ST6 (41.1 %), and ST3 (11.0 %)
      when amplified by PCR using sequenced-tagged site (STS) primers. Four farms had
      goats infected only with ST1 whereas the fifth showed mixed infections with
      multiple STs. The proximity of the fifth farm to human dwellings, nearby
      domesticated animals and grass land as opposed to a sterile captive environment
      in the first four farms may account for the multiple STs seen in the fifth farm.
      Since ST1, ST3, ST6 and ST 7 were previously reported in human infection
      worldwide in particular Malaysia, the potential of the zoonotic transmission of
      blastocystosis should not be disregarded. The implications of different farm
      management systems on the distribution of Blastocystis sp. STs are discussed.

PMID- 22961237
TI  - Sensitivity of two in vitro assays for evaluating plant activity against the
      infective stage of Haemonchus contortus strains.
AB  - The sensitivity of larval paralysis assay (LPA) and 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide-formazan (MTT-formazan) assay was compared to
      evaluate the anthelmintic activity of plant extracts. In this study, the
      methanolic extract of Azadirachta indica (neem) was evaluated for its activity
      against the infective-stage larvae (L(3)) of susceptible and resistant Haemonchus
      contortus strains using the two aforementioned assays. In both in vitro assays,
      the same serial concentrations of the extract were used, and the median lethal
      concentrations were determined to compare the sensitivity of both assays. The
      results revealed a significant difference (P < 0.05) in the sensitivity of the
      LPA and the MTT-formazan assay. The MTT-formazan assay is more feasible for
      practical applications because it measured the L(3) mortality more accurately
      than LPA. This study may help find a suitable assay for investigating the
      anthelmintic activity of plant extracts against trichostrongylid nematodes.

PMID- 22961238
TI  - On the precarious cusp of genetic medicine.
AB  - This is the story of two brothers at the dawn of genetic medicine, the first
      severely disabled by cerebral palsy, the other an MD scientist who happens to
      uncover the genetic cause of his brother's condition. A test confirms their
      mother's carrier status. But what about their only sister--is she a carrier as
      well? The question would send the author down a path she never dreamed she would
      take.

PMID- 22961239
TI  - High expression of calcitonin gene-related peptide and substance P in esophageal
      mucosa of patients with non-erosive reflux disease.
AB  - BACKGROUND: Visceral hypersensitivity is an important etiology of non-erosive
      reflux disease (NERD). Calcitonin gene-related peptide (CGRP) and substance P
      (SP) are involved in the sensitization of afferent neuronal pathways. AIM: The
      objectives of this study were to evaluate visceral hypersensitivity in NERD
      patients, investigate the association between visceral hypersensitivity and
      mucosal expression of SP and CGRP, and assess their involvement in the
      pathogenesis of NERD. METHODS: Twenty-six NERD patients and 12 healthy volunteers
      were recruited. Intraesophageal balloon distention was performed, and initial
      perception threshold (IPT) and threshold of discomfort (ToD) were determined.
      Immunohistochemical staining was used to measure the optical density (OD) of CGRP
      and SP-reactive levels in esophageal mucosa, and the numbers of CGRP and SP
      reactive neural fibers. RESULTS: IPT and ToD were 9.6 +/- 4.8 and 12.3 +/- 3.2
      ml, respectively, in NERD patients, significantly lower than for controls (13.2
      +/- 7.5 and 21.6 +/- 5.7 ml, P < 0.05 and P < 0.01, respectively). Mean OD values
      for CGRP and SP staining were significantly higher in NERD than for controls
      (both P < 0.05) and, in NERD, were negatively correlated with IPT and ToD  (all P
      < 0.01). Numbers of CGRP and SP-reactive neural fibers in esophageal submucosa of
      NERD patients were significantly increased (both P < 0.05). CONCLUSIONS:
      Expression of esophageal epithelial CGRP and SP is increased, and correlates
      negatively with perception thresholds in NERD. These findings may aid
      understanding of peripheral visceral hypersensitivity and the development of new
      therapeutic approaches for management of NERD.

PMID- 22961240
TI  - An inter-observer agreement study of autofluorescence endoscopy in Barrett's
      esophagus among expert and non-expert endoscopists.
AB  - BACKGROUND: Autofluorescence imaging (AFI), which is a "red flag" technique
      during Barrett's surveillance, is associated with significant false positive
      results. The aim of this study was to assess the inter-observer agreement (IOA)
      in identifying AFI-positive lesions and to assess the overall accuracy of AFI.
      METHODS: Anonymized AFI and high resolution white light (HRE) images were
      prospectively collected. The AFI images were presented in random order, followed
      by corresponding AFI + HRE images. Three AFI experts and 3 AFI non-experts scored
      images after a training presentation. The IOA was calculated using kappa and
      accuracy was calculated with histology as gold standard. RESULTS: Seventy-four
      sets of images were prospectively collected from 63 patients (48 males, mean age
      69 years). The IOA for number of AF positive lesions was fair when AFI images
      were presented. This improved to moderate with corresponding AFI and HRE images
      [experts 0.57 (0.44-0.70), non-experts 0.47 (0.35-0.62)]. The IOA for the site of
      AF lesion was moderate for experts and fair for non-experts using AF images,
      which improved to substantial for experts [kappa = 0.62 (0.50-0.72)] but remained
      at fair for non-experts [kappa = 0.28 (0.18-0.37)] with AFI + HRE. Among experts,
      the accuracy of identifying dysplasia was 0.76 (0.7-0.81) using AFI images and
      0.85 (0.79-0.89) using AFI + HRE images. The accuracy was 0.69 (0.62-0.74) with
      AFI images alone and 0.75 (0.70-0.80) using AFI + HRE among non-experts.
      CONCLUSION: The IOA for AF positive lesions is fair to moderate using AFI images
      which improved with addition of HRE. The overall accuracy of identifying
      dysplasia was modest, and was better when AFI and HRE images were combined.

PMID- 22961241
TI  - Killer toxin from a novel killer yeast Pichia kudriavzevii RY55 with
      idiosyncratic antibacterial activity.
AB  - The killer phenomenon of yeast may have technological implications in many areas
      like beverage fermentation, food technology, biological control in agriculture,
      and in medicine. In the present study the killer phenomenon in Pichia
      kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P.
      kudriavzevii RY55 toxin exhibited excellent antibacterial activity against
      several pathogens of human health significance such as Escherichia coli,
      Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas
      aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity
      by using ammonium sulphate precipitation and ion exchange chromatography and
      characterized for few properties. P. kudriavzevii RY55 killer toxin may be of
      vast significance in the development of novel antimicrobial chemotherapeutic
      agents, new bio-based safer candidates for food preservation and biocontrol, and
      starter cultures for fermentation industries. 

PMID- 22961242
TI  - Anterior subtemporal approach for posterolateral brainstem cavernomas: report of
      ten cases.
AB  - BACKGROUND: The neuronavigation-assisted anterior subtemporal approach is
      proposed in this article as an alternative to surgery of posterolateral brainstem
      cavernomas. Brainstem cavernomas represent a neurosurgical challenge because of
      the high morbidity and mortality rate related to their surgical removal. Several
      nerve nuclei, ascending and descending fibers make this region at high risk of
      serious postoperative deficits. METHODS: Between 1998 and 2010, 24 patients
      underwent surgical removal of brainstem cavernomas in our institution. Ten of
      these patients presented a cavernous malformation in the posterolateral region of
      the brainstem and underwent surgical removal by means of a neuronavigation
      assisted anterior subtemporal approach. RESULTS: Lesion removal was complete for
      all patients. There were no cases of surgery-related death. Neurological status
      improved or remained unchanged after surgery in all cases. All patients presented
      good outcomes at 12 to 154 months' follow-up (mean 70 months; GOS = 5 in 8/10
      patients, 4 in 2/10 patients; mRS = 0-1 in all patients). Only one patient
      presented transient confusion, aphasia and seizures related to temporal lobe
      swelling, which resolved completely within a few days. One patient developed
      cranial nerve III palsy and left hemiparesis with gradual recovery. CONCLUSIONS:
      This approach represents a valid alternative to the "more classical" approaches
      for the surgery of posterolateral cavernomas of the pontomesenchephalic junction
      reaching the tentorial incisura, reducing the risk of damaging the vein of Labbe,
      temporal lobe swelling, cerebellar swelling, ophtalmoparesis, fourth ventricle
      cranial nerve nuclei lesions. Skeletonization of sigmoidal sinus provides with
      good outcomes, low morbidity and mortality.

PMID- 22961243
TI  - Deep brain stimulation for treatment of refractory Tourette syndrome: long-term
      follow-up.
AB  - BACKGROUND: Eighteen patients with severe and refractory Tourette Syndrome
      underwent bilateral thalamic deep brain stimulation. The surgical procedures and
      stimulation processes of the cohort were reported in 2008; the 2 year follow-up
      was reported in 2009. The aim of the research is the assessment of long-term
      outcome (5-6 years) on tics, obsessional behaviours, anxiety, mood, and on the
      overall general health of the patients and their general satisfaction. METHOD: In
      this study, all 18 of the original patients will be discussed, pre- and post-DBS,
      according to our protocol using standardized objective schedules, as well as the
      clinical impressions of both clinicians and patients. As there were no
      substantial nor statistical differences on measures of cognitive functioning
      between pre-DBS and 2 year follow-up, we decided not to continue this aspect of
      the formal assessment, particularly as there were also no clinical indications.
      RESULTS: At 5-6 year follow-up, there was a significant reduction in tic severity
      (p < 0.001), and significant improvements in obsessive compulsive behaviours (p =
      0.003), anxiety (p < 0.001) and depressive (p < 0.001) symptoms. Patients, in
      general, required less medication for tics, co-morbid conditions and/or co
      existent psychopathologies. The long-term outcome/satisfaction were not unanimous
      between patients and the medical team. CONCLUSIONS: At long-term follow-up, DBS
      was very successful in terms of a significant improvement in tics and also a
      significant reduction in the potentially disabling symptoms of obsessionality,
      anxiety and depression. However, compared with our more positive overall results
      at 2 years, these later results demonstrate long-term difficulties as follows:
      non-compliance, long-term complications , and the differences in the opinions
      between the (a) medical, (b) the surgical teams and (c) the post-DBS patients as
      to their outcome/satisfaction with the procedures. Our experience highlights the
      need for controlled studies, for long-term follow up, and the need to improve the
      selection of patients for DBS.

PMID- 22961244
TI  - Arterial thrombosis in homozygous antithrombin deficiency.
AB  - Antithrombin (AT), a serin protease inhibitor (serpin) produced in the liver,
      inhibits mainly thrombin and factor Xa. Antithrombin deficiency (AD) is
      associated with a higher incidence of thrombosis. CASE REPORT: We report a
      newborn with uncomplicated birth in the 40+5 week of gestation and postnatal
      appearance of a reticular, livide haematoma on the right upper arm and a tonic
      clonic epileptic seizure. Clinical examination revealed weak pulses in the A.
      radialis and ulnaris. MRI scan showed a large thrombus in the A. carotis interna
      and externa with large cerebral infarction and a thrombus in the A. subclavia.
      Laboratory work up showed elevated D-dimers and antithrombin levels <20% (lowest
      15%), age-related values for protein C, protein S, plasminogen, and no other
      inherited thrombophilia. THERAPY: We started anticoagulation with unfractionated
      heparin intravenously (aPTT: 50-60 s) and under suspicion of an AD the
      substitution of AT (70 U/kg body weight). In course of time we changed
      anticoagulation to low molecular weight heparin (Anti Xa 0.6-0.8 U/ml) and
      substitution of 250 E/kg AT every second day. In the molecular work up we found a
      homozygous missense mutation in exon 2 of SERPINC1 gene (type "Budapest 3").
      Molecular analysis showed also heterozygous mutations in both parents and a
      homozygous mutation in the asymptomatic brother aged three years. At age of six
      months we changed the anticoagulation to coumadin (INR 2.5-3.5). Anticoagulation
      with coumadin was also started in the brother. DISCUSSION: Hereditary AD is
      associated with an increased risk of thrombosis. The homozygous status mainly
      leads to intrauterine fetal loss or the occurrence of peri- and postnatal
      thrombosis. Therapy consists in the substitution of AT and a lifelong
      anticoagulation with vitamin K antagonists also in asymptomatic patients.

PMID- 22961246
TI  - Robust 4C-seq data analysis to screen for regulatory DNA interactions.
AB  - Regulatory DNA elements can control the expression of distant genes via physical
      interactions. Here we present a cost-effective methodology and computational
      analysis pipeline for robust characterization of the physical organization around
      selected promoters and other functional elements using chromosome conformation
      capture combined with high-throughput sequencing (4C-seq). Our approach can be
      multiplexed and routinely integrated with other functional genomics assays to
      facilitate physical characterization of gene regulation.

PMID- 22961245
TI  - Improving FRET dynamic range with bright green and red fluorescent proteins.
AB  - A variety of genetically encoded reporters use changes in fluorescence (or
      Forster) resonance energy transfer (FRET) to report on biochemical processes in
      living cells. The standard genetically encoded FRET pair consists of CFPs and
      YFPs, but many CFP-YFP reporters suffer from low FRET dynamic range,
      phototoxicity from the CFP excitation light and complex photokinetic events such
      as reversible photobleaching and photoconversion. We engineered two fluorescent
      proteins, Clover and mRuby2, which are the brightest green and red fluorescent
      proteins to date and have the highest Forster radius of any ratiometric FRET pair
      yet described. Replacement of CFP and YFP with these two proteins in reporters of
      kinase activity, small GTPase activity and transmembrane voltage significantly
      improves photostability, FRET dynamic range and emission ratio changes. These
      improvements enhance detection of transient biochemical events such as neuronal
      action-potential firing and RhoA activation in growth cones.

PMID- 22961247
TI  - A general approach to break the concentration barrier in single-molecule imaging.
AB  - Single-molecule fluorescence imaging is often incompatible with physiological
      protein concentrations, as fluorescence background overwhelms an individual
      molecule's signal. We solve this problem with a new imaging approach called PhADE
      (PhotoActivation, Diffusion and Excitation). A protein of interest is fused to a
      photoactivatable protein (mKikGR) and introduced to its surface-immobilized
      substrate. After photoactivation of mKikGR near the surface, rapid diffusion of
      the unbound mKikGR fusion out of the detection volume eliminates background
      fluorescence, whereupon the bound molecules are imaged. We labeled the eukaryotic
      DNA replication protein flap endonuclease 1 with mKikGR and added it to
      replication-competent Xenopus laevis egg extracts. PhADE imaging of high
      concentrations of the fusion construct revealed its dynamics and micrometer-scale
      movements on individual, replicating DNA molecules. Because PhADE imaging is in
      principle compatible with any photoactivatable fluorophore, it should have broad
      applicability in revealing single-molecule dynamics and stoichiometry of
      macromolecular protein complexes at previously inaccessible fluorophore
      concentrations.

PMID- 22961248
TI  - Surface chemical functionalization of single walled carbon nanotubes with a
      bacteriorhodopsin mutant.
AB  - In this work, single walled carbon nanotubes (SWNTs) have been chemically
      functionalized at their walls with a membrane protein, namely the mutated
      bacteriorhodopsin D96N, integrated in its native archaeal lipid membrane. The
      modification of the SWNT walls with the mutant has been carried out in different
      buffer solutions, at pH 5, 7.5 and 9, to investigate the anchoring process, the
      typical chemical and physical properties of the component materials being
      dependent on the pH. The SWNTs modified by interactions with bacteriorhodopsin
      membrane patches have been characterized by UV-vis steady state, Raman and
      attenuated total reflection Fourier transform infrared spectroscopy and by atomic
      force and transmission electron microscopy. The investigation shows that the
      membrane protein patches wrap the carbon walls by tight chemical interactions
      undergoing a conformational change; such chemical interactions increase the
      mechanical strength of the SWNTs and promote charge transfers which p-dope the
      nano-objects. The functionalization, as well as the SWNT doping, is favoured in
      acid and basic buffer conditions; such buffers make the nanotube walls more
      reactive, thus catalysing the anchoring of the membrane protein. The direct
      electron communication among the materials can be exploited for effectively
      interfacing the transport properties of carbon nanotubes with both molecular
      recognition capability and photoactivity of the cell membrane for sensing and
      photoconversion applications upon integration of the achieved hybrid materials in
      sensors or photovoltaic devices.

PMID- 22961254
TI  - Interletter spacing and dyslexia.

PMID- 22961255
TI  - Optimum inhomogeneity of local lattice distortions in La2CuO(4+y).
AB  - Electronic functionalities in materials from silicon to transition metal oxides
      are, to a large extent, controlled by defects and their relative arrangement.
      Outstanding examples are the oxides of copper, where defect order is correlated
      with their high superconducting transition temperatures. The oxygen defect order
      can be highly inhomogeneous, even in optimal superconducting samples, which
      raises the question of the nature of the sample regions where the order does not
      exist but which nonetheless form the "glue" binding the ordered regions together.
      Here we use scanning X-ray microdiffraction (with a beam 300 nm in diameter) to
      show that for La(2)CuO(4+y), the glue regions contain incommensurate modulated
      local lattice distortions, whose spatial extent is most pronounced for the best
      superconducting samples. For an underdoped single crystal with mobile oxygen
      interstitials in the spacer La(2)O(2+y) layers intercalated between the CuO(2)
      layers, the incommensurate modulated local lattice distortions form droplets
      anticorrelated with the ordered oxygen interstitials, and whose spatial extent is
      most pronounced for the best superconducting samples. In this simplest of high
      temperature superconductors, there are therefore not one, but two networks of
      ordered defects which can be tuned to achieve optimal superconductivity. For a
      given stoichiometry, the highest transition temperature is obtained when both the
      ordered oxygen and lattice defects form fractal patterns, as opposed to appearing
      in isolated spots. We speculate that the relationship between material complexity
      and superconducting transition temperature T(c) is actually underpinned by a
      fundamental relation between T(c) and the distribution of ordered defect networks
      supported by the materials.

PMID- 22961256
TI  - Revisiting the contribution of negative charges on the chaperonin cage wall to
      the acceleration of protein folding.
AB  - Chaperonin GroEL mediates the folding of protein encapsulated in a GroES-sealed
      cavity (cage). Recently, a critical role of negative charge clusters on the cage
      wall in folding acceleration was proposed based on experiments using GroEL single
      ring (SR) mutants SR1 and SRKKK2 [Tang YC, et al. (2006) Cell 125:903-914;
      Chakraborty K, et al. (2010) Cell 142:112-122]. Here, we revisited these
      experiments and discovered several inconsistencies. (i) SR1 was assumed to bind
      to GroES stably and to mediate single-round folding in the cage. However, we show
      that SR1 repeats multiple turnovers of GroES release/binding coupled with ATP
      hydrolysis. (ii) Although the slow folding observed for a double-mutant of
      maltose binding protein (DMMBP) by SRKKK2 was attributed to mutations that
      neutralize negative charges on the cage wall, we found that the majority of DMMBP
      escape from SRKKK2 and undergo spontaneous folding in the bulk medium. (iii) An
      osmolyte, trimethylamine N-oxide, was reported to accelerate SRKKK2-mediated
      folding of DMMBP by mimicking the effect of cage-wall negative charges of WT
      GroEL and ordering the water structure to promote protein compaction. However, we
      demonstrate that in-cage folding by SRKKK2 is unaffected by trimethylamine N
      oxide. (iv) Although it was reported that SRKKK2 lost the ability to assist the
      folding of ribulose-1,5-bisphosphate carboxylase/oxygenase, we found that SRKKK2
      retains this ability. Our results argue against the role of the negative charges
      on the cage wall of GroEL in protein folding. Thus, in chaperonin studies,
      folding kinetics need to be determined from the fraction of the real in-cage
      folding.

PMID- 22961257
TI  - Delayed initiation of front-line imatinib therapy predicts for poor response to
      nilotinib as second-line treatment of imatinib-resistant or intolerant CML:
      single center report of the ENACT trial in Lebanon.

PMID- 22961258
TI  - Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease
      Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics
      Project.
AB  - Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC)
      and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP),
      started during the late 2000s with the aim to deliver a comprehensive assessment
      of phenotypes or to screen for robust indicators of diseases in mouse mutants.
      They both took advantage of available mouse mutant lines but predominantly of the
      embryonic stem (ES) cells resources derived from the European Conditional Mouse
      Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce
      and study 799 mouse models that were systematically analysed with a comprehensive
      set of physiological and behavioural paradigms. They captured more than 400
      variables and an additional panel of metadata describing the conditions of the
      tests. All the data are now available through EuroPhenome database
      (www.europhenome.org) and the WTSI mouse portal
      (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are
      available through the European Mouse Mutant Archive (EMMA), the International
      Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP)
      Repository. Overall conclusions from both studies converged, with at least one
      phenotype scored in at least 80% of the mutant lines. In addition, 57% of the
      lines were viable, 13% subviable, 30% embryonic lethal, and 7% displayed
      fertility impairments. These efforts provide an important underpinning for a
      future global programme that will undertake the complete functional annotation of
      the mammalian genome in the mouse model.

PMID- 22961260
TI  - A comparison of two methods of endoscopic dilation of acute subglottic stenosis
      using a ferret model.
AB  - OBJECTIVES/HYPOTHESIS: Balloon dilation is accepted as a first line treatment of
      acute subglottic stenosis, but its effects on the subglottic tissue remain
      largely unknown. We aimed to develop an animal model of acute subglottic stenosis
      using endoscopic techniques. Once developed, this model was used to compare the
      immediate effects of balloon dilation and endotracheal tube dilation on
      subglottic tissue. STUDY DESIGN: Prospective randomized animal study. METHODS:
      Acute subglottic injury was induced in 10 ferrets by endoscopic cauterization
      with silver nitrate. After 48-72 hours of observation, eight animals were
      randomized to undergo subglottic dilation with either a 5-mm balloon or
      endotracheal tubes of increasing diameter. These eight ferrets were euthanized
      within 10 minutes after dilation. The other two ferrets served as controls and
      were euthanized following observation only. The larynx from each ferret was
      harvested, and the subglottis was examined histologically by a pathologist
      blinded to the treatment arms. RESULTS: Acute subglottic stenosis was induced in
      all 10 ferrets using the endoscopic technique. Both balloon and endotracheal tube
      dilation resulted in comparable improvement in the subglottic airway diameter. A
      decreased thickness of submucosa/lamina propria was seen in the balloon dilation
      group. CONCLUSIONS: Acute subglottic stenosis can be reliably induced in ferrets
      using endoscopic techniques. Multiple dilation methods can be used to relieve
      acute obstruction. Balloon dilators seem to improve airway patency, in part, by
      decreasing the thickness of the submucosa and lamina propria. Further research is
      needed to determine how this impacts later stages of wound healing and final
      outcomes.

PMID- 22961259
TI  - The Mammalian Phenotype Ontology as a unifying standard for experimental and high
      throughput phenotyping data.
AB  - The Mammalian Phenotype Ontology (MP) is a structured vocabulary for describing
      mammalian phenotypes and serves as a critical tool for efficient annotation and
      comprehensive retrieval of phenotype data. Importantly, the ontology contains
      broad and specific terms, facilitating annotation of data from initial
      observations or screens and detailed data from subsequent experimental research.
      Using the ontology structure, data are retrieved inclusively, i.e., data
      annotated to chosen terms and to terms subordinate in the hierarchy. Thus,
      searching for "abnormal craniofacial morphology" also returns annotations to
      "megacephaly" and "microcephaly," more specific terms in the hierarchy path. The
      development and refinement of the MP is ongoing, with new terms and modifications
      to its organization undergoing continuous assessment as users and expert
      reviewers propose expansions and revisions. A wealth of phenotype data on mouse
      mutations and variants annotated to the MP already exists in the Mouse Genome
      Informatics database. These data, along with data curated to the MP by many mouse
      mutagenesis programs and mouse repositories, provide a platform for comparative
      analyses and correlative discoveries. The MP provides a standard underpinning to
      mouse phenotype descriptions for existing and future experimental and large-scale
      phenotyping projects. In this review we describe the MP as it presently exists,
      its application to phenotype annotations, the relationship of the MP to other
      ontologies, and the integration of the MP within large-scale phenotyping
      projects. Finally we discuss future application of the MP in providing standard
      descriptors of the phenotype pipeline test results from the International Mouse
      Phenotype Consortium projects.

PMID- 22961261
TI  - Conductive polymer foam surface improves the performance of a capacitive EEG
      electrode.
AB  - In this paper, a new conductive polymer foam-surfaced electrode was proposed for
      use as a capacitive EEG electrode for nonintrusive EEG measurements in out-of
      hospital environments. The current capacitive electrode has a rigid surface that
      produces an undefined contact area due to its stiffness, which renders it unable
      to conform to head curvature and locally isolates hairs between the electrode
      surface and scalp skin, making EEG measurement through hair difficult. In order
      to overcome this issue, a conductive polymer foam was applied to the capacitive
      electrode surface to provide a cushioning effect. This enabled EEG measurement
      through hair without any conductive contact with bare scalp skin. Experimental
      results showed that the new electrode provided lower electrode-skin impedance and
      higher voltage gains, signal-to-noise ratios, signal-to-error ratios, and
      correlation coefficients between EEGs measured by capacitive and conventional
      resistive methods compared to a conventional capacitive electrode. In addition,
      the new electrode could measure EEG signals, while the conventional capacitive
      electrode could not. We expect that the new electrode presented here can be
      easily installed in a hat or helmet to create a nonintrusive wearable EEG
      apparatus that does not make users look strange for real-world EEG applications.

PMID- 22961262
TI  - Dynamic understanding of human-skin movement and strain-field analysis.
AB  - Understanding the skin's material properties and natural motion is critical to a
      myriad of applications from tissue engineering to spacesuits. While there is an
      extensive understanding of human skin properties based on active tensile testing,
      both in vitro and in vivo, there is a little current knowledge of the strains
      experienced by skin during natural movements. Using a motion capture system, we
      have developed a new technique to measure skin movement and strain around the
      knee during a squatting motion. With these new data, we are also able to
      calculate the local direction of lines of nonextension, or contours of the skin
      that remain a constant length during motion, lines of minimum extension, and
      lines of minimum compression.

PMID- 22961264
TI  - Metabolic changes in the spinal cord after brachial plexus root re-implantation.
AB  - OBJECTIVE: To investigate metabolic changes within the spinal cord using proton
      magnetic resonance spectroscopy ((1)H-MRS) and determine their relationship with
      clinical function in patients with complete brachial plexus avulsion who
      underwent reimplantation of the ventral roots. METHODS: Single-voxel (1)H-MRS of
      the cord between C1 and C3 was performed in 10 patients with normal spinal cord
      on MRI, who underwent reimplantation of C5 to T1 ventral roots on average 5.5
      years earlier, and 19 healthy controls. The ratios of the concentrations of the
      following main metabolites, with respect to total creatine levels, were obtained:
      total N-acetyl-aspartate, choline-containing compounds, creatine and
      phosphocreatine (Cr), and myo-inositol (m-Ins). Patient disability was assessed
      using upper limb scales. Differences in metabolite concentration ratios and their
      correlations with disability were investigated. RESULTS: Patients showed
      increased m-Ins/Cr ratio compared with controls, which was associated with the
      level of function of the affected arm and time from injury. CONCLUSIONS: The
      finding of increased m-Ins/Cr in patients suggests that reactive gliosis, perhaps
      in response to the degeneration of avulsed fibers, may occur in the spinal cord
      above the site of injury and be relevant to motor dysfunction. However, this
      pathological process appears to diminish with time. These insights underline the
      need to integrate metabolic imaging with structural and functional magnetic
      resonance imaging to obtain a complete view of spinal cord plasticity. Last, this
      study provides the first steps toward identifying markers to serve as outcome
      measures for trials comparing strategies of plexus repair following avulsion
      injury.

PMID- 22961263
TI  - Recovery from poststroke visual impairment: evidence from a clinical trials
      resource.
AB  - INTRODUCTION: Limited evidence suggests that visual impairments may influence
      outcome after stroke. The degree of recovery from these impairments is poorly
      characterized. OBJECTIVES: To describe recovery and to determine whether visual
      impairments influence functional outcome and quality of life. METHODS: We
      extracted demographic and outcome data from the Virtual International Stroke
      Trials Archive (VISTA). We examined horizontal eye movement disorders and
      hemianopia using the Best Gaze and Visual domains of the National Institutes of
      Health Stroke Scale (NIHSS) and described recovery at 30 and 90 days.
      Proportional odds modelling was used to examine the association between
      impairments at baseline, modified Rankin Scale (mRS), and European Quality of
      Life Score (EQ-5D) at 90 days. RESULTS: Visual impairments were reported in
      7,204/11,900 (60.5%) patients at baseline. Complete recovery occurred in
      1,398/3,285 (42.6%) and 3,243/7,204 (45.0%) patients by 30 and 90 days
      respectively. The burden of persistent visual impairment in survivors was
      1,135/4,028 (28.2%) at 30 days and 1,915/9,338 (20.5%) at 90 days. Partial gaze
      palsy (P < .0001; OR = 0.81; 95% CI = 0.74-0.87), forced deviation (P < .0001; OR
      = 0.48; 95% CI = 0.43-0.53), and complete homonymous hemianopia (P < .0001; OR =
      0.67; 95% CI = 0.62-0.73) at baseline were associated with poor mRS at 90 days.
      CONCLUSIONS: The rate of recovery was greater in the first month after stroke,
      suggesting a potential time frame for interventions. The associations between
      visual impairments and poor mRS suggest that these impairments should be
      considered in multidisciplinary assessments and interventions.

PMID- 22961265
TI  - Nitric oxide regulates cytokine induction in the diaphragm in response to
      inspiratory resistive breathing.
AB  - Resistive breathing (encountered in chronic obstructive pulmonary disease and
      asthma) results in cytokine upregulation and decreased nitric oxide (NO) levels
      in the strenuously contracting diaphragm. NO can regulate gene expression. We
      hypothesized that endogenously produced NO downregulates cytokine production
      triggered by strenuous diaphragmatic contraction. Wistar rats treated with
      vehicle, the nonselective NO synthase inhibitor NG-nitro-l-arginine-methylester
      (l-NAME), or the NO donor diethylenetriamine-NONOate (DETA) were subjected to
      inspiratory resistive breathing (IRB; 50% of maximal inspiratory pressure) for 6
      h or sham operation. Additional groups of rats were subjected to IRB for 6 h with
      concurrent administration of l-NAME and inhibitors of NF-kappaB (BAY-11-7082),
      ERK1/2 (PD98059), or P38 (SB203580). Inhibition of NO production (with l-NAME)
      resulted in upregulation of IRB-induced diaphragmatic IL-6, IL-10, IL-2, TNF
      alpha, and IL-1beta levels by 50%, 53%, 60%, 47%, and 45%, respectively. In
      contrast, the NO donor (DETA) attenuated the IRB-induced cytokine upregulation to
      levels characteristic of quietly breathing animals. l-NAME augmented IRB-induced
      activation of MAPKs (P38 and ERK1/2) and NF-kappaB, whereas DETA triggered the
      opposite effect. NF-kappaB and ERK1/2 inhibition in l-NAME-treated animals
      blunted the l-NAME-induced cytokine upregulation except IL-6, whereas P38
      inhibition blunted all (including IL-6) cytokine upregulation. NO downregulates
      IRB-induced cytokine production in the strenuously contracting diaphragm through
      its action on MAPKs and NF-kappaB.

PMID- 22961266
TI  - Defining the characteristic relationship between arterial pressure and cerebral
      flow.
AB  - Reliable assessment of cerebrovascular effectiveness in buffering against
      pressure fluctuations may have important implications for the timing and the
      outcome of therapy after adverse cerebrovascular events. Although linear
      approaches may indicate the presence or absence of cerebral autoregulation, they
      are inadequate to describe its characteristics and its effectiveness.
      Establishing a simple yet robust methodology to reliably measure the
      effectiveness of cerebral autoregulation could provide a tool to guide screening
      and clinical options to characterize and treat adverse cerebrovascular events
      associated with alterations in cerebral perfusion. To test the utility of one
      such methodology, an oscillatory lower body negative pressure of 30-40 mmHg was
      used at six frequencies from 0.03 to 0.08 Hz in 43 healthy volunteers, and the
      pressure-flow relation and the effectiveness of autoregulation was quantified
      using projection pursuit regression. Projection pursuit regression explained the
      majority of the relationship between pressure and cerebral blood flow
      fluctuations and revealed its nature consistently across individuals and across
      separate study days. The nature of this relationship entailed an autoregulatory
      region wherein slow arterial pressure fluctuations are effectively
      counterregulated and two passive regions wherein pressure fluctuations resulted
      in parallel changes in flow. The effectiveness of autoregulation was
      significantly reduced as pressure fluctuations became faster. These results
      demonstrate the characteristic relationship between arterial pressure and
      cerebral blood flow. Furthermore, the methodology utilized in this study provides
      a tool that can provide unique insight to integrated cerebrovascular control and
      may allow diagnosis of physiological alterations underlying impaired cerebral
      autoregulation.

PMID- 22961267
TI  - Influence of alpha-adrenergic vasoconstriction on the blunted skeletal muscle
      contraction-induced rapid vasodilation with aging.
AB  - We tested the hypothesis that elevated sympathetic tone is responsible for lower
      peak vasodilation after single muscle contractions in older adults. Young (n =
      13, 7 men and 6 women, age: 27 +/- 1 yr) and older (n = 13, 7 men and 6 women,
      age: 69 +/- 2 yr) adults performed single forearm contractions at 10%, 20%, and
      40% of maximum during 1) control, 2) sympathetic activation via lower body
      negative pressure (LBNP; -20 mmHg), and 3) intra-arterial infusion of
      phentolamine (alpha-adrenergic antagonist). Brachial artery diameter and
      velocities were measured via Doppler ultrasound, and forearm vascular conductance
      (FVC; in ml.min(-1).100 mmHg(-1)) was calculated from blood flow (in ml/min) and
      blood pressure (in mmHg). Peak vasodilator responses [change in (Delta) FVC from
      baseline] were attenuated in older adults at 20% and 40% of maximum (P < 0.05).
      LBNP reduced peak DeltaFVC at 10% (98 +/- 17 vs. 70 +/- 12 ml.min(-1).100 mmHg(
      1)), 20% (144 +/- 12 vs. 98 +/- 3 ml.min(-1).100 mmHg(-1)), and 40% (209 +/- 20
      vs. 161 +/- 21 ml.min(-1).100 mmHg(-1), P < 0.01 vs. control) in younger adults
      but not in older adults (71 +/- 11 vs. 68 +/- 11, 107 +/- 13 vs. 106 +/- 16, and
      161 +/- 22 vs. 144 +/- 22 ml.min(-1).100 mmHg(-1), respectively, P = 0.22-0.99).
      With phentolamine, peak DeltaFVC was enhanced in older adults at each contraction
      intensity (100 +/- 14, 147 +/- 22, and 200 +/- 26 ml.min(-1).100 mmHg(-1),
      respectively, P < 0.01 vs. control) but not in younger adults (94 +/- 13, 153 +/-
      13, and 224 +/- 27 ml.min(-1).100 mmHg(-1), respectively, P = 0.30-0.81 vs.
      control). Our data indicate that alpha-adrenergic vasoconstriction and/or blunted
      functional sympatholysis might contribute to the age-related decreases in
      skeletal muscle contraction-induced rapid vasodilation in humans.

PMID- 22961269
TI  - Motor cortex and corticospinal excitability in humans with a history of illicit
      stimulant use.
AB  - Illicit use of stimulant drugs such as methamphetamine, ecstasy, and cocaine is a
      current and growing problem throughout the world. The aim of the current study
      was to investigate the long-term effect of illicit stimulant use on human motor
      cortical and corticospinal circuitry. We hypothesized that individuals with a
      history of primarily methamphetamine and ecstasy use would exhibit altered
      corticospinal excitability and intracortical inhibition within motor cortex. The
      study involved 52 healthy adults (aged 26 +/- 7 yr) comprising 26 abstinent
      stimulant users, 9 cannabis users, and 17 nondrug users. The experiment involved
      a routine urine drug screen, drug history questionnaire, neuropsychological
      assessment, and single- and paired-pulse transcranial magnetic stimulation (TMS)
      over motor cortex. EMG responses to stimulation [motor evoked potentials (MEPs)]
      were recorded from the contralateral first dorsal interosseus. At a given
      stimulus intensity, MEP area was significantly larger in abstinent stimulant
      users than in nondrug users during both relaxation (P = 0.045) and muscle
      contraction (P < 0.001). MEP latency was also significantly longer in abstinent
      stimulant users (P < 0.009), and they exhibited significantly greater muscle
      activity during performance of a given task (P = 0.004). However, resting motor
      threshold and the response to paired-pulse TMS were unaffected. The results
      suggest that abstinent stimulant users exhibit long-term changes in the
      excitability of motor cortical and corticospinal circuitry and muscle activity
      during movement. These changes may partly underlie anecdotal and objective
      reports of movement dysfunction in chronic stimulant users.

PMID- 22961268
TI  - Adjustments of pulmonary O2 uptake and muscle deoxygenation during ramp
      incremental exercise and constant-load moderate-intensity exercise in young and
      older adults.
AB  - The matching of muscle O(2) delivery to O(2) utilization can be inferred from the
      adjustments in muscle deoxygenation (Delta[HHb]) and pulmonary O(2) uptake
      (Vo(2p)). This study examined the adjustments of Vo(2p) and Delta[HHb] during
      ramp incremental (RI) and constant-load (CL) exercise in adult males. Ten young
      adults (YA; age: 25 +/- 5 yr) and nine older adults (OA; age: 70 +/- 3 yr)
      completed two RI tests and six CL step transitions to a work rate (WR)
      corresponding to 1) 80% of the estimated lactate threshold (same relative WR) and
      2) 50 W (same absolute WR). Vo(2p) was measured breath by breath, and Delta[HHb]
      of the vastus lateralis was measured using near-infrared spectroscopy. Delta[HHb]
      WR profiles were normalized from baseline (0%) to peak Delta[HHb] (100%) and fit
      using a sigmoid function. The sigmoid slope (d) was greater (P < 0.05) in OA
      (0.027 +/- 0.01%/W) compared with YA (0.017 +/- 0.01%/W), and the c/d value (a
      value corresponding to 50% of the amplitude) was smaller (P < 0.05) for OA (133
      +/- 40 W) than for YA (195 +/- 51 W). No age-related differences in the sigmoid
      parameters were reported when WR was expressed as a percentage of peak WR. Vo(2p)
      kinetics compared with Delta[HHb] kinetics for the 50-W transition were similar
      between YA and OA; however, Delta[HHb] kinetics during the transition to 80% of
      the lactate threshold were faster than Vo(2p) kinetics in both groups. The
      greater reliance on O(2) extraction displayed in OA during RI exercise suggests a
      lower O(2) delivery-to-O(2) utilization relationship at a given absolute WR
      compared with YA.

PMID- 22961270
TI  - Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation
      during heat stress in humans.
AB  - VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and
      pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors
      sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all
      implicated in cutaneous active vasodilation (AVD) through incompletely defined
      mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are
      synergistic and interdependent in AVD and tested our hypothesis by examining the
      effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during
      heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating
      peptide 6-38 (PACAP6-38) and the NOS inhibitor, N(G)-nitro-l-arginine methyl
      ester (l-NAME) were administered by intradermal microdialysis. PACAP6-38, l-NAME,
      a combination of PACAP6-38 and l-NAME, or Ringer's solution alone were perfused
      at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry
      at each site. Body temperature was controlled with water-perfused suits. Blood
      pressure was monitored by Finapres, and cutaneous vascular conductance (CVC)
      calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol
      began with a 5- to 10-min baseline period without antagonist perfusion, followed
      by perfusion of PACAP6-38, l-NAME, or combined PACAP6-38 and l-NAME at the
      different sites in normothermia (45 min), followed by 3 min of whole body
      cooling. Whole body heating was then performed to induce heat stress and activate
      AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect
      maximal vasodilation for normalization of blood flow data. No significant
      differences in CVC (normalized to maximum) were found among Ringer's PACAP6-38, l
      NAME, or combined antagonist sites during normothermia (P > 0.05 among sites) or
      cold stress (P > 0.05 among sites). CVC responses at all treated sites were
      attenuated during AVD (P < 0.05 vs. Ringer's). Attenuation was greater at l-NAME
      and combined PACAP6-38- and l-NAME-treated sites than at PACAP6-38 sites (P >
      0.05). Because responses did not differ between l-NAME and combined treatment
      sites (P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to
      effect AVD.

PMID- 22961272
TI  - Local administration of growth hormone stimulates tendon collagen synthesis in
      elderly men.
AB  - Tendon collagen content and circulating growth hormone (GH) are reduced in
      elderly. In a placebo-controlled, double-blinded study, we examined if local
      injections of rhGH enhance collagen synthesis in healthy elderly men (61 +/- 1
      yr). Two injections of rhGH or saline (control) were injected into each of the
      patient's patellar tendons, respectively. Subsequently, tendon collagen
      fractional synthesis rate (FSR) and an indirect marker of type I collagen
      synthesis (PINP) were measured. Within the first 6 h after the last injections, a
      tendency towards a higher tendon collagen FSR was observed in 10 out of 12
      subjects (P = 0.08). Similarly, PINP was higher 3-4 h after the last GH injection
      (P = 0.05). Serum IGF-I did not change from baseline, whereas peritendinous
      bioactive IGF-I was higher in the GH leg vs. control (P = 0.05). In conclusion,
      local injections of rhGH increase tendon collagen synthesis in humans, either
      directly or indirectly by increasing local bioactive IGF-I.

PMID- 22961271
TI  - Phrenic long-term facilitation after acute intermittent hypoxia requires spinal
      ERK activation but not TrkB synthesis.
AB  - Acute intermittent hypoxia (AIH) elicits a form of spinal respiratory plasticity
      known as phrenic long-term facilitation (pLTF). pLTF requires spinal serotonin
      receptor-2 activation, the synthesis of new brain-derived neurotrophic factor
      (BDNF), and the activation of its high-affinity receptor tyrosine kinase, TrkB.
      Spinal adenosine 2A receptor activation elicits a distinct pathway to phrenic
      motor facilitation (pMF); this BDNF synthesis-independent pathway instead
      requires new synthesis of an immature TrkB isoform. Since hypoxia increases
      extracellular adenosine levels, we tested the hypothesis that new synthesis of
      TrkB and BDNF contribute to AIH-induced pLTF. Furthermore, given that signaling
      mechanisms "downstream" from TrkB are unknown in either mechanism, we tested the
      hypothesis that pLTF requires MEK/ERK and/or phosphatidylinositol 3-kinase
      (PI3K)/Akt activation. In anesthetized Sprague-Dawley rats, an intrathecal
      catheter at cervical level 4 was used to deliver drugs near the phrenic motor
      nucleus. Since pLTF was blocked by spinal injections of small interfering RNAs
      targeting BDNF mRNA but not TrkB mRNA, only new BDNF synthesis is required for
      AIH-induced pLTF. Pretreatment with a MEK inhibitor (U0126) blocked pLTF, whereas
      a PI3K inhibitor (PI-828) had no effect. Thus, AIH-induced pLTF requires MEK/ERK
      (not PI3K/AKT) signaling pathways. When U0126 was injected post-AIH, pLTF
      development was halted but not reversed, suggesting that ERK is critical for the
      development but not maintenance of pLTF. Thus, there are clear mechanistic
      distinctions between AIH-induced pLTF (i.e., BDNF synthesis and MEK/ERK
      dependent) versus adenosine 2A receptor-induced pMF (i.e., TrkB synthesis and
      PI3K/Akt dependent).

PMID- 22961273
TI  - Management of asymptomatic, severe mitral regurgitation.
AB  - OPINION STATEMENT: In chronic, severe mitral regurgitation (MR), cardiac function
      can remain well compensated and patients can remain asymptomatic for many years.
      Eventually, in most patients, the originally favorable loading conditions give
      way to unfavorable remodeling, which results in left ventricular (LV) dysfunction
      and dilation, and ultimately symptoms of pulmonary congestion. Symptomatic,
      chronic severe MR is a clear indication for surgical correction. However, the
      optimal management of asymptomatic patients is less clear. While asymptomatic
      severe MR patients who have developed LV dysfunction or LV dilation warrant
      surgery, the decision to operate without these findings hinges on the presence of
      other clinical sequelae, such as atrial arrhythmias and pulmonary hypertension,
      and on the likelihood of successful mitral valve repair. Controversy exists as to
      the optimal approach to patients without any of these objective triggers, with
      some evidence supporting earlier prophylactic surgery and other evidence
      supporting a "watch and wait" approach. It is our conviction that in absence of
      an established guideline-based indication for surgical correction, for most
      asymptomatic patients with chronic severe MR, the preferred approach is close
      monitoring with serial echocardiography for development of symptoms or other
      clinical sequelae. However, it is reasonable to consider earlier surgical
      correction in select asymptomatic patients in whom there is a high likelihood of
      successful mitral valve repair. In this paper, we comprehensively review all
      guideline-based management of asymptomatic chronic severe MR, and discuss new
      evidence that impacts clinical decision-making in these patients.

PMID- 22961275
TI  - [The future of mental health care].

PMID- 22961274
TI  - Endostatin, an inhibitor of angiogenesis, decreases after bidirectional superior
      cavopulmonary anastamosis.
AB  - Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity
      after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of
      hepatic venous effluent away from the pulmonary circulation after Glenn appears
      to play a significant role in the pathogenesis of PAVMs. Although the liver is
      known to produce factors that regulate vascular development, specific hepatic
      inhibitors of angiogenesis have not been described in the post-Glenn population.
      Endostatin, produced from its precursor collagen XVIII, is a potent inhibitor of
      angiogenesis produced by the liver. This study aimed to investigate the
      hypothesis that endostatin levels decrease in patients after Glenn. Levels of
      endostatin and its precursor, long-type collagen XVIII, were determined by enzyme
      linked immunoassay and immunoprecipitation, respectively, for serum samples from
      38 patients undergoing Glenn, total cavopulmonary anastomosis (Fontan), or
      biventricular repair of cardiac defects. Samples were obtained before surgery and
      24 h afterward. In patients undergoing a bidirectional Glenn procedure,
      endostatin levels decreased after surgery (n = 17; 4.42 vs 3.34 ng/ml; p <
      0.001), and long type-collagen XVIII levels increased by 200 % (n = 10; p =
      0.0001). However, endostatin levels did not change after surgery in patients
      undergoing Fontan (n = 13) or biventricular repair (n = 8). In patients
      undergoing Fontan, long-type collagen XVIII increased by 18 % (p < 0.01), whereas
      in control subjects, the levels were unchanged. These data suggest that the
      diversion of hepatic blood flow away from the pulmonary circulation in patients
      after the Glenn procedure inhibits endostatin production from collagen XVIII,
      resulting in decreased circulating serum endostatin levels. A decrease in
      endostatin may promote angiogenesis. The mechanism whereby the pulmonary
      circulation processes endostatin and its potential role in the pathogenesis of
      PAVMs warrant further study.

PMID- 22961276
TI  - [Regional differences in the care and treatment of compulsory admissions in the
      Netherlands].
AB  - BACKGROUND: In the Netherlands compulsory admissions are on the increase.
      However, there are regional differences even when demographic factors are taken
      into account. AIM: To find out whether there are regional differences in the type
      and duration of care given to detainees. METHOD: On the basis of case-register
      data for Groningen, South Limburg, Utrecht and Rotterdam, we monitored the
      psychiatric history and aftercare that followed emergency compulsory admissions
      and we analysed the differences between patient groups ('old acquaintances',
      'newcomers' and 'passers-by'). RESULTS: Almost 60% of patients were well known to
      the mental health care service and had previously received psychiatric care. 85%
      of the patients were still receiving care three months after admission. Even when
      patient and admission characteristics were taken into account, there were still
      regional variations in the type and length of mental health care episodes before
      and after compulsory admission. CONCLUSION: The continuity of health care for
      emergency admissions in the context of the Dutch Mental Health Act varies from
      region to region. It remains to be seen whether the situation will change when
      the new Mental Health Act comes into force.

PMID- 22961277
TI  - [Recognition of psychiatric disorders with a religious content by members of the
      clergy     of different denominations in the Netherlands].
AB  - BACKGROUND: Clergy members (CMS) frequently provide support and counselling for
      people with psychological and psychiatric disorders. There is evidence in the
      literature that CMS consider themselves to be inadequately trained to recognise
      psychiatric disorders. AIM: To investigate to what extent CMS are able to
      recognise psychiatric symptoms. METHOD: CMS were recruited in the south-west of
      the Netherlands among various denominations (Roman Catholic, strict (orthodox)
      Protestant, moderate Protestant and Evangelical; n = 143) by means of a regional
      sampling method. The participating CMS (n = 143) and a control group consisting
      of mental health care professionals MPHS; n = 73) evaluated four vignettes of
      psychiatric problems with a religious content: two were about a psychiatric
      disorder (a psychotic state and a psychotic depression/melancholic state), and
      two concerned non-psychiatric states (a spiritual/religious experience and a
      mourning reaction with a religious dilemma). For each vignette the respondents
      scored the suitability of psychiatric medication, the desirability of mental
      health care, the severity of the disorder and whether there was a religious or
      spiritual aetiology. RESULTS: Some CMS were able to recognise psychiatric
      problems almost as well as the MHPS, but among the CMS the degree of recognition
      varied according to the denomination. Recognition was relatively poor among
      Evangelical CMS, but was best among the strict Protestant CMS. Evangelical
      pastors and strict Protestant CMS tended to interpret the non-psychiatric states
      as pathological. CONCLUSION: The findings of this study emphasise the need for
      collaboration between MHPS and CMS and stress the importance of consultation.

PMID- 22961278
TI  - [Managing aggression in a forensic psychiatric unit for adolescents: literature
      review and clinical implementation].
AB  - BACKGROUND: Aggressive incidents are part and parcel of everyday life in a
      forensic psychiatric unit for adolescents. AIM: To review the literature about
      the prevalence of aggressive incidents and about aggression management policy in
      (forensic) child and adolescent psychiatry and to explain and elaborate the
      aggression management protocol in a newly established unit. METHOD: The
      literature was reviewed systematically using PubMed and PsycINFO in order to
      locate studies in English and Dutch published since 1990. RESULTS: Only 10
      publications reported prevalence data on aggressive incidents in child or
      adolescent psychiatric units. Literature about concrete policy guidelines was
      almost non-existent. 27% to 78% of the youngsters had been involved in some kind
      of aggression. The lack of clear definitions and the differences in the research
      designs made a reliable comparison impossible. CONCLUSION: To date, there is no
      evidence that a greater number of aggressive incidents occur in a forensic
      psychiatric unit for adolescents than in a regular adolescent psychiatric unit.
      Further research into both the prevalence and the characteristics of incidents is
      required in order to provide cues for a good policy. This policy will need to
      include structural and relational security measures that are firmly supported by
      the systematic registration of incidents and by continuous risk assessment.

PMID- 22961279
TI  - [DSM-5 and culture].
AB  - BACKGROUND: The leading diagnostic classification system used in the Dutch mental
      health care system is the DSM-IV(Diagnostic and Statistical Manual of Mental
      Disorders). The next version, DSM-5, will probably be published in 2013. The new
      version aims to pay more attention to cultural diversity; this will have
      implications for treatment and research. AIM: To discuss the most important
      aspects of DSM-5 that have culture relevance. METHOD: A Medline search was
      conducted for the period 1990- 2011 on the basis of the search terms 'DSM',
      'ICD', 'DSM-classification, 'psychiatric classification', 'psychiatric
      diagnosis', 'culture' and 'diversity'. RESULTS: Taking the example of depression
      and anxiety, one must conclude that the diagnostic system does not achieve its
      aims. It might be possible to compensate for this shortcoming by introducing a
      dimensional-categorical system. Such a system would be particularly important for
      cultural psychiatry and psychology in relation to matters such as subsyndromal
      symptom categories, experience of illness, behaviour during illness, the
      transition from normality to deviancy, culturally responsive research, and links
      to cultural neuroscience. CONCLUSION: It looks as if such a major paradigm shift
      will not occur until DSM-6.

PMID- 22961280
TI  - [Psychiatric diagnostics, the 'cultural interview' and DSM-5].

PMID- 22961281
TI  - [How much do patients know about the possible physical consequences of their
      eating disorder?].
AB  - BACKGROUND: A lack of knowledge about the physical consequences of an eating
      disorder can be a sign that the patient either denies that there is a problem or
      minimises the problem; this can result in the patient being reluctant or
      unwilling to be treated. AIM: To find out how much patients know about the
      possible physical consequences of (or the risks involved in) their eating
      disorder and to check whether they know considerably more after some psycho
      education. METHOD: Sixty-six female patients completed a questionnaire shortly
      after being admitted to a specialised eating-disorder unit and 44 patients
      completed the same questionnaire after about a month. In the intervening period
      patients received some psycho-education about the possible physical consequences
      of eating disorders. The psycho-education took the form of an interactive group
      session and a brochure of information. RESULTS: In general, the patients'
      knowledge about possible consequences of their illness was reasonably
      satisfactory (on average, 14 out of 20 questions were correct), although a
      considerable number of patients answered 11 questions with 'I don't know'. In the
      second round there was a considerable decrease in the number of 'I don't know'
      answers, showing that after a month patients' knowledge had improved (17 out of
      20 patients now gave positive answers); the answers were independent of the type
      of eating disorder. One question in particular elicited the largest number of
      uncertain or incorrect answers, even in the second round; the question was: Can a
      woman who has never menstruated become pregnant?' CONCLUSION: It is advisable to
      assess, in a systematic way, whether patients have adequate knowledge about the
      physical consequences of an eating disorder. Gaps in patients' knowledge or
      misunderstandings can then serve as a starting point for a specific type of
      psycho-education.

PMID- 22961282
TI  - [A case study; ethnicity and clozapine, a risky combination?].
AB  - Agranulocytosis is a very serious side-effect of treatment with clozapine. For
      this reason, the Dutch guidelines state the specific values of leukocyte and
      neutrophil counts at which treatment with clozapine should be discontinued. We
      focus on a patient with a benign ethnic neutropenia who, despite a low neutrophil
      count, was allowed to continue taking clozapine. We discuss a number of important
      practical considerations that can affect the way in which leukocyte and
      neutrophil counts are interpreted in relation to the use of clozapine.

PMID- 22961283
TI  - [Reaction on 'the ethical duty to treat children and adolescents with autism and
      catatonia'].

PMID- 22961284
TI  - [Reaction on 'emergency compulsory admission in crisis situations; the Amsterdam
      Study of Acute Psychiatry].

PMID- 22961285
TI  - Uterine artery Doppler velocimetry and obstetric outcomes in connective tissue
      diseases diagnosed during the first trimester of pregnancy.
AB  - OBJECTIVE: To evaluate the effect of connective tissue disease (CTD) diagnosed
      during the first trimester on uterine arteries (UtA) Doppler velocities and on
      pregnancy outcomes. METHOD: Pregnant women were screened for CTDs during the
      first trimester, using a questionnaire, testing for autoantibodies, rheumatologic
      examination and UtA Doppler evaluations. RESULTS: Out of 3932 women screened, 491
      (12.5%) were screened positive at the questionnaire; of them, 165(33.6%) tested
      positive for autoantibodies, including 66 eventually diagnosed with
      undifferentiated connective tissue disease (UCTD), 28 with a definite CTD and 71
      with insufficient criteria for a diagnosis. Controls were 326 women screened
      negative for autoantibodies. In logistic analysis, women diagnosed with either
      UCTD (OR = 7.9, 95% CI = 2.3-27.3) or overt CTD (OR = 24.9, 95% CI = 6.7-92.4),
      had increased rates of first trimester bilateral UtA notches compared with
      controls. The rates of bilateral UtA notches persisting in the second (15/94 vs
      0/326, p < 0.001) and third trimesters (7/94 vs 0/326, p < .001) were higher
      among women with CTDs than in controls. The risk of complications (preeclampsia,
      fetal growth restriction, prematurity, diabetes, fetal loss) was higher (OR =
      7.8, 95% CI = 3.6-17.0) among women with CTDs than in controls. CONCLUSION: Women
      with undiagnosed CTDs have higher rates of bilateral UtA Doppler notches
      throughout pregnancy and increased rates of adverse pregnancy outcomes than
      controls.

PMID- 22961286
TI  - Iridium nanoparticles stabilized by metal organic frameworks (IrNPs@ZIF-8):
      synthesis, structural properties and catalytic performance.
AB  - Today, the synthesis of well-defined metal nanoparticles stabilized by the metal
      organic frameworks (MOFs), which provide high specific surface areas, tunable
      pore sizes, and guest interactable organic linkers, and the discovery of their
      unique properties are still challenging goals. The chemically robust zeolitic
      imidazole framework (ZIF) is a subclass of MOF. In this study, the microporous
      sodalite-like ZIF-8 (Zn(MeIM); MeIM = 2-methylimidazole) was selected as host
      matrix to stabilize guest iridium nanoparticles (IrNPs). The iridium loading was
      achieved via gas phase infiltration of Ir(COD)(MeCp) (methylcyclopentadienyl)(1,5
      cyclooctadiene)iridium(i)) precursor followed by hydrogenolysis of the inclusion
      compound Ir(COD)(MeCp)@ZIF-8 to form the IrNPs@ZIF-8. The characterization of
      IrNPs@ZIF-8 by ICP-MS, P-XRD, XPS, (13)C MAS NMR, TEM, HRTEM, STEM, STEM-EDX,
      HAADF-STEM, DR-UV-vis, EA analyses and N(2)-adsorption-desorption techniques
      reveal the formation of well-dispersed iridium nanoparticles (3.3 +/- 1.7 nm)
      within the framework of ZIF-8 (IrNPs@ZIF-8) by keeping the host framework intact.
      The catalytic application of IrNPs@ZIF-8 in terms of activity, selectivity,
      reusability and durability was demonstrated in the hydrogenation of cyclohexene
      and phenylacetylene under mild conditions, in which they were found to be highly
      active catalysts. Moreover, they show great durability against sintering and
      leaching throughout the catalytic runs that make them highly reusable catalysts.
      They retain their inherent catalytic activity even at the fifth catalytic run in
      the hydrogenation of cyclohexene and phenylacetylene.

PMID- 22961287
TI  - What works where? A systematic review of child and adolescent mental health
      interventions for low and middle income countries.
AB  - PURPOSE: Child and adolescent mental health (CAMH) problems are common and
      serious all over the world and are linked to pre-mature deaths and serious
      dysfunction in adult life. Effective interventions have been developed in high
      income countries (HIC), but evidence from low income settings is scarce and
      scattered. The aim of this paper is to identify the most promising interventions
      in the area of global CAMH. METHOD: A systematic review of all randomised
      controlled trials in CAMH in low and middle income countries (LAMIC) was carried
      out and supplemented by 1a level evidence from HIC as well as suitable
      information from child programme evaluations and adult studies in LAMIC. RESULTS:
      In behavioural disorders parent training is a highly promising intervention,
      which can successfully improve children's compliance and bring down rates of
      conduct problems significantly. In young children cognitive, emotional and
      behavioural development can be enhanced through nutritional supplements and by
      stimulation through play, praise and reading. Trauma treatments can bring
      positive results even in severely traumatised children, who remain in unstable
      living conditions. In developmental disorders, there are successful prevention
      strategies as well as programmes that bring children out of isolation and improve
      their independence. Some classroom-based interventions for adolescents have
      reduced symptoms of common mental disorders as well as risk taking behaviours.
      CONCLUSIONS: While many results are still tentative the evidence suggests that it
      is possible to develop affordable and feasible interventions that significantly
      improve the lives of affected children, their families and their communities
      around the world.

PMID- 22961288
TI  - Are attitudes towards medication adherence associated with medication adherence
      behaviours among patients with psychosis? A systematic review and meta analysis.
AB  - BACKGROUND: Studies have shown patient attitudes to be an important predictor for
      health related behaviours including medication adherence. It is less clear
      whether patient attitudes are also associated with medication adherence among
      patients with psychoses. METHOD: We conducted a systematic review and meta
      analysis of the data of studies that tested the association of attitude measures
      with medication adherence among patients with psychoses. 14 studies conducted
      between 1980 and 2010 were included. RESULTS: Results show a small to moderate
      mean weighted effect size (r (+) = 0.25 and 0.26 for Pearson and Spearman
      correlations, respectively). CONCLUSIONS: Theory based interventions that target
      potentially modifiable attitude components are needed to assess the relationship
      between positive patient attitudes and adherence behaviours among patients with
      psychoses.

PMID- 22961289
TI  - Patterns of lifetime female victimisation and psychotic experiences: a study
      based on the UK Adult Psychiatric Morbidity Survey 2007.
AB  - PURPOSE: Research has shown that sexual trauma represents a specific threat for
      psychosis, particularly among females. Sexual trauma among females, however, has
      also been shown to enhance the risk for further revictimisation. Females are
      likely to exhibit distinct lifetime trauma profiles, i.e. female sexual trauma
      victims are often more likely to experience particular forms of re-victimisation,
      such as intimate partner and domestic violence. METHODS: This study used data
      from the Adult Psychiatric Morbidity Survey (2007) to profile lifetime histories
      of sexual trauma and domestic violence among female participants (N = 4,111).
      RESULTS: The latent class analysis revealed four lifetime victimisation classes:
      (i) a multiple victimisation class; (ii) an intimate partner victimisation class;
      (iii) a sexual victimisation class; and (iv) a victimisation-free class.
      Multivariate logistic regression revealed that there was a strong association
      between class membership and a diagnosis of psychosis and that the victimisation
      classes were significantly associated with all psychotic-like experiences.
      Compared to the victimisation-free class, the multiple victimisation class
      displayed an increased likelihood of experiencing all psychotic experiences
      except mania. The intimate partner victimisation class was also associated with
      an increased likelihood of experiencing all psychotic experiences; however, the
      odds ratios for this class were lower than those recorded for the multiple
      victimisation class. CONCLUSIONS: These findings reflect female-specific
      variation in both victimisation history and psychosis-related vulnerability.
      Acknowledging such sex-specific variation may advance our understanding of the
      complex associations that continue to emerge between trauma and psychosis for
      both males and females.

PMID- 22961290
TI  - Country of birth and hospital treatment for psychosis in New South Wales.
AB  - BACKGROUND: Migration has been found to be a risk factor for schizophrenia in
      several high-income countries. AIM: To examine whether overseas migrants to New
      South Wales (NSW) have higher rates of admission to psychiatric hospitals for
      psychotic disorders, including schizophrenia and mania, compared to people born
      in Australia. METHODS: The country of birth of people admitted to public mental
      health units for the treatment of psychotic illness and for non-psychotic
      disorders between 2001 and 2010 was compared to the country of birth for the NSW
      population in the 2006 census. Meta-analysis was used to estimate the odds of
      being admitted for any psychotic disorder, for a schizophrenia-related psychosis
      and for mania compared to non-psychotic disorder, for those born in Australia,
      New Zealand and for nine global regions. RESULTS: Those born in Oceania
      (including Melanesia, Fiji, Samoa, Tonga and other Polynesian islands, but
      excluding Hawaii and New Zealand) had the highest odds of admission for the
      treatment of psychosis compared to a non-psychotic disorder and had the highest
      odds of being admitted with a diagnosis of schizophrenia or mania. CONCLUSIONS:
      In the years 2001-2010, those born in Oceania were at an increased risk of
      admission to NSW psychiatric hospitals for the treatment of psychotic illness.

PMID- 22961291
TI  - Collaborative Care Skills Training workshops: helping carers cope with eating
      disorders from the UK to Australia.
AB  - PURPOSE: The Collaborative Care Skills Training workshops, developed by Treasure
      and associates aim to improve the well-being, coping strategies and problem
      solving skills of carers of someone with an eating disorder. Evidence has
      demonstrated the effectiveness of the workshops in the UK where it was developed.
      The aim of this pilot study was to examine whether conducting the workshops in
      different contexts by facilitators trained in its delivery could lead to similar
      impact. METHODS: The workshops were conducted with 15 carers in VIC, Australia
      and delivered by experienced health professionals trained in its content and
      delivery. A non-experimental research design with repeated measures was
      implemented. Quantitative data were collected at pre-and post-intervention and 8
      weeks after completion of the workshops. RESULTS: Participation led to
      significant reductions in carers' reported expressed emotion, dysfunctional
      coping, distress, burden and accommodation and enabling of the eating disorder
      behaviour, which were maintained at the 8-week follow-up. CONCLUSION: Results
      suggest the workshops are effective in reducing carer distress and burden as well
      as modifying unhelpful emotional interactional styles when caring for family
      members with an eating disorder. The content of the workshops and its delivery,
      once experienced facilitators have received training, are transferable to other
      contexts.

PMID- 22961292
TI  - Clusters according to patient need in a long-stay inpatient population with
      schizophrenia: does executive dysfunction underpin needs-directed care?
AB  - PURPOSE: To identify the external validators of patient clusters according to
      need in a long-stay inpatient population with schizophrenia. METHODS: We
      recruited without exclusion 112 in-patients with chronic schizophrenia in a long
      stay rehabilitation facility of a major psychiatric hospital in Perth, Western
      Australia. Case managers completed a number of measures for participants,
      including The Camberwell Assessment of Need-Short Appraisal Schedule, which
      evaluates health and social needs. Latent class analysis according to patient
      need was performed to identify clusters within the cohort. One way analysis of
      variance was used to identify the external validators of these clusters, using
      variables obtained from the additional study measures (Social Behaviour Schedule,
      Global Assessment of Function, Basic Everyday Living Skills, Behaviour Rating
      Inventory of Executive Function-Adult version). RESULTS: Three distinct needs
      based clusters with different external profiles were identified. A "low unmet
      needs" group (n = 50) with relatively intact executive function, with the least
      problematic behaviour and most independent functioning; a "high unmet need (drug
      abstinent)" group (n = 43) with greatest executive dysfunction, most problematic
      behaviour and least independent function; a "high unmet need (drug using)" group
      (n = 19), with less severe executive dysfunction, and intermediate relative to
      the other groups on measures of social behaviour and independent functioning.
      CONCLUSIONS: The clinical heterogeneity we have identified, which may well be
      explained by executive dysfunction, suggests further exploration of appropriate
      assessment and streams of care for those in the rehabilitation setting is
      warranted.

PMID- 22961294
TI  - Detecting hoof lesions in dairy cattle using a hand-held thermometer.

PMID- 22961293
TI  - Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic
      review and meta-analysis.
AB  - Available literature suggests that both vitamin D and calcium may be associated
      with a wide range of non-skeletal outcomes. However, epidemiological evidence
      supporting their individual associations with incident cerebrovascular disease is
      scarce. We conducted a systematic review and meta-analysis of prospective cohort
      studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS
      and the Science Citation Index databases, and reported cerebrovascular disease
      (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke,
      cerebrovascular accident or transient ischemic attack) by circulating vitamin D
      (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two
      independent investigators abstracted information on 25(OH)D and calcium,
      cerebrovascular outcomes and other characteristics from selected studies.
      Relative risks (RRs) were pooled by both random and fixed effects meta-analyses
      and were further examined under different study-level characteristics.
      Publication bias was assessed with funnel plots and Egger's asymmetry test. From
      5,778 initial references, nine unique prospective cohort studies met our
      inclusion criteria. Seven studies (involving 47,809 participants and 926
      cerebrovascular events) focused on circulating 25(OH)D and 3 reported on
      circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a
      comparison of individuals in the top third versus those in the bottom third at
      baseline, the combined RR for cerebrovascular disease, adjusted for several
      conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in
      the prospective studies that reported on baseline circulating calcium levels for
      cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent
      evidence of heterogeneity or publication bias among included studies. Available
      data indicate that higher circulating level of vitamin D is associated with a
      decreased risk of cerebrovascular disease. Conversely, higher circulating calcium
      concentration is associated with an increased risk of cerebrovascular disease.

PMID- 22961295
TI  - Knowledge of obesity and its impact on reproductive health outcomes among urban
      women.
AB  - This prospective survey study assessed the knowledge of reproductive outcomes
      that are affected by obesity among women in an urban community. A total of 207
      women attending a community fair on the south side of Chicago participated in the
      study. A survey assessing knowledge of BMI and of the effects of obesity on
      general, cardiometabolic and reproductive health outcomes was administered.
      Subjects ranged in age from 18 to 70 years (mean +/- SD, 48.6 +/- 12.9 years) and
      ranged in BMI from 17.3 to 52.1 kg/m(2) (mean +/- SD, 31.2 +/- 6.7 kg/m(2)). The
      following percentages of women were aware that obesity increases the risk of
      miscarriage (37.5 %), irregular periods (35.8 %), infertility (33.9 %), cesarean
      section (30.8 %), breast cancer (28.0 %), birth defects (23.7 %), stillbirth
      (14.1 %), and endometrial cancer (18.1 %). This study found that while women in
      an urban community are aware of the cardiometabolic risks associated with
      obesity, they demonstrate limited knowledge of the effects of obesity on
      reproductive outcomes. Public education is needed to increase knowledge and
      awareness of the reproductive consequences of obesity. Women of reproductive age
      may be uniquely responsive to obesity education and weight loss intervention.

PMID- 22961296
TI  - Performance of lactating dairy cows fed a diet based on treated rice straw and
      supplemented with pelleted sweet potato vines.
AB  - The purpose of this study was to evaluate the effects of sweet potato vine pellet
      (SWEPP) in concentrate diets on nutrient digestibility and rumen ecology in
      lactating dairy cows fed on urea-treated rice straw. Three multiparous Holstein
      crossbred cows in mid-lactation were randomly assigned according to a 3 * 3 Latin
      square design, and the treatments were as follows: T1 = control (no
      supplementation), T2 = supplementation of sweet potato vine pellet with 50 g/kg
      urea (SWEPP I) at 300 g/head/day, and T3 = supplementation of sweet potato pellet
      with 100 g/kg urea (SWEPP II) at 300 g/head/day, in concentrate diets,
      respectively. The result revealed that supplementation of SWEPP did not affect
      feed intake, ruminal pH, and blood urea nitrogen (P > 0.05). However, apparent
      digestibilities of organic matter, crude protein, and neutral detergent fiber
      were higher in SWEPP II than those in others. Furthermore, ruminal ammonia
      nitrogen (NH(3)-N) and milk yield were significantly higher (P < 0.05) in animals
      fed with SWEPP II than those fed with SWEPP I and control, respectively. In
      addition, there were no differences in purine derivatives and microbial nitrogen
      supply among all the treatments. Based on this study, it could be concluded that
      SWEPP is a good source of supplement which resulted in significant improvement in
      apparent digestibility, rumen fermentation, and milk yield in lactating dairy
      cows fed on urea-treated rice straw.

PMID- 22961297
TI  - Automatic coronary calcium scoring in low-dose chest computed tomography.
AB  - The calcium burden as estimated from non-ECG-synchronized computed tomography
      (CT) exams acquired in screening of heavy smokers has been shown to be a strong
      predictor of cardiovascular events. We present a method for automatic coronary
      calcium scoring with low-dose, non-contrast-enhanced, non-ECG-synchronized chest
      CT. First, a probabilistic coronary calcium map was created using multi-atlas
      segmentation. This map assigned an a priori probability for the presence of
      coronary calcifications at every location in a scan. Subsequently, a statistical
      pattern recognition system was designed to identify coronary calcifications by
      texture, size, and spatial features; the spatial features were computed using the
      coronary calcium map. The detected calcifications were quantified in terms of
      volume and Agatston score. The best results were obtained by merging the results
      of three different supervised classification systems, namely direct
      classification with a nearest neighbor classifier, and two-stage classification
      with nearest neighbor and support vector machine classifiers.We used a total of
      231 test scans containing 45,674 mm3 of coronary calcifications. The presented
      method detected on average 157/198 mm3 (sensitivity 79.2%) of coronary calcium
      volume with on average 4 mm false positive volume. Calcium scoring can be
      performed automatically in low-dose, non-contrast enhanced, non-ECG-synchronized
      chest CT in screening of heavy smokers to identify subjects who might benefit
      from preventive treatment.

PMID- 22961298
TI  - Improved modelling of tool tracking errors by modelling dependent marker errors.
AB  - Accurate understanding of equipment tracking error is essential for decision
      making in image guided surgery. For tools tracked using markers attached to a
      rigid body, existing error estimation methods use the assumption that the
      individual marker errors are independent random variables. This assumption is not
      valid for all tracking systems. This paper presents a method to estimate a more
      accurate tracking error function, consisting of a systematic and random
      component. The proposed method does not require detailed knowledge of the
      tracking system physics. Results from a pointer calibration are used to
      demonstrate that the proposed method provides a better match to observed results
      than the existing state of the art. A simulation of the pointer calibration
      process is then used to show that existing methods can underestimate the pointer
      calibration error by a factor of two. A further simulation of laparoscopic camera
      tracking is used to show that existing methods cannot model important variations
      in system performance due to the angular arrangement of the tracking markers. By
      arranging the markers such that the systematic errors are nearly identical for
      all markers, the rotational component of the tracking error can be reduced,
      resulting in a significant reduction in target tracking errors.

PMID- 22961299
TI  - [Incidence of thromboembolic events after major operations in patients with
      haemophilia].
AB  - Thromboembolic complications may occur in patients with major operations even
      after routine thromboprophylaxis with low-molecular-weight-heparin. In this
      retrospective, single center survey the post-operative course of patients with
      haemophilia was investigated. PATIENTS, METHODS: Overall, the postoperative
      course in 85 patients with haemophilia A and B (median age: 43 years, 18-73
      years) and 139 surgical procedures was analyzed. The surgical procedures mainly
      consist of major orthopedic surgery (58 total knee replacement, 15 hip
      replacement, 17 other major orthopedic surgery, 15 minor orthopedic procedures).
      Additional surgical procedures were abdominal-surgical (18), urological (8),
      neurosurgical (5). RESULTS: During the post-operative observation period a small
      number of wound healing complications occurred (4%). None of the patients
      developed symptomatic deep vein thrombosis or lung embolism. CONCLUSION: There
      seems to a decreased risk of postoperative thromboembolism in patients with
      haemophilia.

PMID- 22961300
TI  - Molecular cloning and functional characterization of a Delta6-fatty acid
      desaturase gene from Rhizopus oryzae.
AB  - The objective was to screen for and isolate a novel enzyme with the specific
      activity of a Delta6-fatty acid desaturase from Rhizopus oryzae. In this study,
      R. oryzae was identified as a novel fungal species that produces large amounts of
      gamma-linolenic acid. A full-length cDNA, designated here as RoD6D, with high
      homology to fungal Delta6-fatty acid desaturase genes was isolated from R. oryzae
      by using the rapid amplification of cDNA ends method. It had an open reading
      frame of 1176 bp encoding a deduced polypeptide of 391 amino acids.
      Bioinformatics analysis characterized the putative RoD6D protein as a typical
      membrane-bound desaturase, including three conserved histidine-rich motifs, a
      hydropathy profile, and a cytochrome b5 -like domain in the N terminus. When the
      coding sequence was expressed in the Saccharomyces cerevisiae strain INVScl, the
      encoded product of RoD6D exhibited Delta6-fatty acid desaturase activity that led
      to the accumulation of gamma-linolenic acid. The corresponding genomic sequence
      of RoD6D was 1565 bp in length, with five introns. This is the first report on
      the characterization and gene cloning of a Delta6-fatty acid desaturase of R.
      oryzae from Douchi. 

PMID- 22961301
TI  - Differential gene expression pattern in early gastric cancer by an integrative
      systematic approach.
AB  - To elucidate the molecular basis of early gastric cancer (EGC), the genome-wide
      expression pattern of cancer and normal tissues from 27 patients were analyzed by
      a microarray-based method. Using an integrative systematic bioinformatics
      approach, we classified the differentially expressed genes in EGC. Interestingly,
      the more highly expressed genes in EGC exhibited the most significant correlation
      with cell migration and metastasis. This implies that, even at the early stage of
      gastric cancer, the molecular properties usually observed in late-stage cancer
      are already present. Furthermore, we have found a novel association between the
      expression pattern and molecular pathways of EGC and estrogen receptor alpha
      (ERalpha)-negative breast cancer through cross-experimental analysis. These
      results provide new insights into the biological properties of EGC, as well as
      yielding useful basic data for the study of molecular mechanisms of EGC
      carcinogenesis.

PMID- 22961302
TI  - Cyclic strain amplitude dictates the growth response of vascular smooth muscle
      cells in vitro: role in in-stent restenosis and inhibition with a sirolimus drug
      eluting stent.
AB  - The putative effects of changes in mean strain and cyclic strain amplitude on
      vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) were
      examined. Subsequently, a quantitative measure of vSMC growth was obtained to
      determine the prolonged effect of changes in mechanical burden following bare
      metal stent (BMS) and sirolimus drug-eluting stent (DES) deployment in vitro.
      Bovine aortic vSMCs were exposed to prolonged cyclic strain using a
      Flexercell(TM) Tension system and a novel Sylgard(TM) phantom vessel following
      stent implantation before the level of vSMC proliferation and apoptosis was
      assessed by FACS analysis, cell counting, and immunocytochemistry. Physiological
      cyclic strain (5%) decreased vSMC proliferation and increased apoptosis in a
      temporal manner. There was no significant difference in cell growth following
      exposure to varying mean strains with similar amplitude. In contrast, exposure to
      varying strain amplitudes with similar mean strains resulted in significant
      differences in cell proliferation and apoptosis. In parallel studies, the level
      of vSMC proliferation and cell survival was significantly increased within low
      amplitude, high mean strain regions of a phantom vessel following BMS
      implantation when compared to regions of higher strain amplitude upstream and
      downstream of the stent, respectively. Moreover, the level of vSMC growth within
      the stented region was significantly attenuated following implantation of a
      sirolimus-coated DES independent of significant changes in cell survival. Cyclic
      strain amplitude is an important regulator of vSMC growth capacity within a stent
      and is a target for inhibition using a sirolimus-coated DES. 

PMID- 22961303
TI  - On the physiological significance of alternative splicing events in higher
      plants.
AB  - Alternative splicing, which generates multiple transcripts from the same gene and
      potentially different protein isoforms, is a key posttranscriptional regulatory
      mechanism for expanding proteomic diversity and functional complexity in higher
      eukaryotes. The most recent estimates, based on whole transcriptome sequencing,
      indicate that about 95 % of human and 60 % of Arabidopsis multi-exon genes
      undergo alternative splicing, suggesting important roles for this mechanism in
      biological processes. However, while the misregulation of alternative splicing
      has been associated with many human diseases, its biological relevance in plant
      systems is just beginning to unfold. We review here the few plant genes for which
      the production of multiple splice isoforms has been reported to have a clear in
      vivo functional impact. These case studies implicate alternative splicing in the
      control of a wide range of physiological and developmental processes, including
      photosynthetic and starch metabolism, hormone signaling, seed germination, root
      growth and flowering, as well as in biotic and abiotic stress responses. Future
      functional characterization of alternative splicing events and identification of
      the transcripts targeted by major regulators of this versatile means of
      modulating gene expression should uncover the breadth of its physiological
      significance in higher plants.

PMID- 22961304
TI  - Site- and alignment-controlled growth of graphene nanoribbons from nickel
      nanobars.
AB  - Graphene nanoribbons combine the unique electronic and spin properties of
      graphene with a transport gap that arises from quantum confinement and edge
      effects. This makes them an attractive candidate material for the channels of
      next-generation transistors. Nanoribbons can be made in a variety of ways,
      including lithographic, chemical and sonochemical approaches, the unzipping of
      carbon nanotubes, the thermal decomposition of SiC and organic synthesis.
      However, the reliable site and alignment control of nanoribbons with high on/off
      current ratios remains a challenge. Here we control the site and alignment of
      narrow (~23 nm) graphene nanoribbons by directly converting a nickel nanobar into
      a graphene nanoribbon using rapid-heating plasma chemical vapour deposition. The
      nanoribbons grow directly between the source and drain electrodes of a field
      effect transistor without transfer, lithography and other postgrowth treatments,
      and exhibit a clear transport gap (58.5 meV), a high on/off ratio (>10(4)) and no
      hysteresis. Complex architectures, including parallel and radial arrays of
      supported and suspended ribbons, are demonstrated. The process is scalable and
      completely compatible with existing semiconductor processes, and is expected to
      allow integration of graphene nanoribbons with silicon technology.

PMID- 22961305
TI  - Nanoparticles: Imaging electrocatalysts in action.

PMID- 22961306
TI  - Current-induced magnetic domain wall motion below intrinsic threshold triggered
      by Walker breakdown.
AB  - Controlling the position of a magnetic domain wall with electric current may
      allow for new types of non-volatile memory and logic devices. To be practical,
      however, the threshold current density necessary for domain wall motion must be
      reduced below present values. Intrinsic pinning due to magnetic anisotropy, as
      recently observed in perpendicularly magnetized Co/Ni nanowires, has been shown
      to give rise to an intrinsic current threshold J(th)(0). Here, we show that
      domain wall motion can be induced at current densities 40% below J(th)(0) when an
      external magnetic field of the order of the domain wall pinning field is applied.
      We observe that the velocity of the domain wall motion is the vector sum of
      current- and field-induced velocities, and that the domain wall can be driven
      against the direction of a magnetic field as large as 2,000 Oe, even at currents
      below J(th)(0). We show that this counterintuitive phenomenon is triggered by
      Walker breakdown, and that the additive velocities provide a unique way of
      simultaneously determining the spin polarization of current and the Gilbert
      damping constant.

PMID- 22961307
TI  - Toward an Axiomatic Definition of Conflict Between Belief Functions.
AB  - Recently, the problem of measuring the conflict between two bodies of evidence
      represented by belief functions has known a regain of interest. In most works
      related to this issue, Dempster's rule plays a central role. In this paper, we
      propose to study the notion of conflict from a different perspective. We start by
      examining consistency and conflict on sets and extract from this settings basic
      properties that measures of consistency and conflict should have. We then extend
      this basic scheme to belief functions in different ways. In particular, we do not
      make any a priori assumption about sources (in)dependence and only consider such
      assumptions as possible additional information. 

PMID- 22961308
TI  - Human-Centered Design and Evaluation of Haptic Cueing for Teleoperation of
      Multiple Mobile Robots.
AB  - In this paper, we investigate the effect of haptic cueing on a human operator's
      performance in the field of bilateral teleoperation of multiple mobile robots,
      particularly multiple unmanned aerial vehicles (UAVs). Two aspects of human
      performance are deemed important in this area, namely, the maneuverability of
      mobile robots and the perceptual sensitivity of the remote environment. We
      introduce metrics that allow us to address these aspects in two psychophysical
      studies, which are reported here. Three fundamental haptic cue types were
      evaluated. The Force cue conveys information on the proximity of the commanded
      trajectory to obstacles in the remote environment. The Velocity cue represents
      the mismatch between the commanded and actual velocities of the UAVs and can
      implicitly provide a rich amount of information regarding the actual behavior of
      the UAVs. Finally, the Velocity+Force cue is a linear combination of the two. Our
      experimental results show that, while maneuverability is best supported by the
      Force cue feedback, perceptual sensitivity is best served by the Velocity cue
      feedback. In addition, we show that large gains in the haptic feedbacks do not
      always guarantee an enhancement in the teleoperator's performance. 

PMID- 22961309
TI  - Synthesis of beta-C-galactosyl D- and L-alanines.
AB  - Synthesis of beta-C-D-galactosyl D- and L-alanines is carried out via a highly
      stereoselective Grignard reaction of glycosyl iodides, Sharpless dihydroxylation
      and S(N)2 displacement of the corresponding mesylate or tosylate. Alternatively,
      attempted triflation of the intermediate alcohols triggers a stereoselective
      debenzylative cyclization leading to interesting bicyclic trans-fused compounds.

PMID- 22961310
TI  - Non-invasive diagnosis for Philometra ovata (Nematoda) infection in the common
      minnow Phoxinus phoxinus.
AB  - Non-invasive diagnoses for most of the extraintestinal helminth infections among
      vertebrates are rare. In the present study, we developed and tested a non
      invasive visual diagnosis method to detect the infection of the nematode
      Philometra ovata, which is parasitising in the body cavity of the common minnow
      Phoxinus phoxinus. By observing the surface of minnow's abdomen, we diagnosed
      infected minnows with irregular or vermiform-shaped uplifts as a consequence of
      the presence of P. ovata in the body cavity. We conducted the diagnosis in
      minnows with or without anaesthetisation, and our results showed the non-invasive
      method is highly reliable (correct rate of diagnoses > 95 %) in both
      anaesthetised and non-anaesthetised groups. The correct rate of diagnoses in
      truly uninfected fish (i.e. specificity) was nearly 100 % in both groups, while
      the correct rate of diagnoses in truly infected fish (i.e. sensitivity) was 71
      and 65 % in anaesthetised and non-anaesthetised fish, respectively. The correct
      rate in fish diagnosed as infected or uninfected (i.e. positive or negative
      predictive power) of non-invasive diagnosis was nearly 100 % among the
      anaesthetised fish, and over 95 % in non-anaesthetised group. The diagnosis also
      yielded prevalence of P. ovata infection similar to the real prevalence in
      anaesthetised fish. Diagnoses conducted by an inexperienced observer indicated
      that the method is repeatable. Taken together, the present non-invasive method
      seems to be a promising new tool for non-invasive detection of P. ovata
      infections in minnows and probably can be applied for the detection of other body
      cavity dwelling metazoan parasites in various host taxa.

PMID- 22961312
TI  - Application of real-time loudness models can improve speech recognition for
      cochlear implant users.
AB  - The aim of cochlear implant (CI) stimulation strategies is to appropriately
      encode the important aspects of sound into a pattern of electrical stimulation.
      Recent research using numerical models of loudness perception has identified that
      there are large differences between how loudness is encoded by existing CI sound
      processing strategies and how loudness is experienced by normally hearing
      listeners. In this paper, we present a new CI sound-coding algorithm aimed at
      addressing these discrepancies. This strategy, named SCORE, uses models of
      electric and acoustic loudness to modify the output of an existing CI sound
      processing scheme in real time, so that the loudness changes are more accurately
      represented in the patterns of electrical stimulation. Five subjects (six
      implanted ears) were tested for understanding of speech presented at relatively
      low levels in quiet conditions. Using SCORE, subjects demonstrated an average 8.8
      percentage-point statistically significant improvement   in the number of words
      correctly identified relative to ACE, a commonly used stimulation strategy. These
      findings show that loudness changes over time are important for speech
      intelligibility, and that improving loudness coding in existing CI devices may
      lead to perceptual benefits.

PMID- 22961311
TI  - Antineoplastic drug, carboplatin, protects mice against visceral leishmaniasis.
AB  - In the present study, the leishmanicidal effect of two doses (5 and 10 mg/kg body
      weight) of the carboplatin was studied in Leishmania donovani-infected BALB/c
      mice. Mice were infected intracardially with promastigotes of L. donovani, and a
      month after infection, they were treated intraperitoneally with the two doses of
      the drug (5 and 10 mg/kg body weight) for five continuous days. Animals were
      sacrificed on 1 and 15 posttreatment days. Hepatic parasite load was assessed on
      Geimsa-stained imprints. Immune responses were studied by measuring delayed-type
      hypersensitivity (DTH) responses, serum IgG isotype levels (IgG1 and IgG2a) and
      cytokine levels [gamma-interferon (IFN-gamma), interleukin (IL)-10 and IL-2] in
      spleen cell cultures by ELISA. To study the drug-induced side effects, various
      haematological (haemoglobin and total leukocyte count), biochemical (liver and
      kidney function tests) and histological investigations (kidney, liver and spleen)
      were carried out. The antileishmanial potential of the drug was revealed by
      significant reduction in the parasite burden. The infected and treated animals
      were also found to exhibit increased DTH responses, higher IgG2a levels, lower
      IgG1 levels and greater cytokine (IFN-gamma, IL-10 and IL-2) concentrations
      pointing towards the generation of mixed Th1/Th2 response. Liver and kidney
      function tests and histological studies of kidney, liver and spleen of treated
      mice revealed no side effects. Carboplatin cures mice of visceral leishmaniasis
      without causing any serious side effects, and the drug was found be more
      effective at a dose of 10 mg/kg body weight as compared to 5 mg/kg body weight.

PMID- 22961314
TI  - Preadolescent disordered eating predicts subsequent eating dysfunction.
AB  - OBJECTIVE: This article tested whether disordered eating in the spring of sixth
      grade can be predicted by the behaviors of fifth grade elementary school
      children. METHOD: Measurements of disordered eating were collected from 1906
      children (mean age = 10.86 years) at Time 1 (spring of fifth grade), Time 2 (fall
      of sixth grade), and Time 3 (spring of sixth grade). RESULTS: A number of fifth
      grade children reported disordered eating during the previous 2 weeks: 12.1%
      reported objective binge episodes, 4.8% reported purging food, and 9.8% reported
      restricting food intake. These behaviors predicted disordered eating during the
      spring of sixth grade. In addition, fifth grade pubertal onset predicted higher
      levels of restricting for girls. CONCLUSION: A substantial number of fifth grade
      children reported disordered eating behaviors, and these behaviors predicted
      disordered eating behaviors in the spring of sixth grade. Disordered eating can
      be studied at least as early as fifth grade.

PMID- 22961315
TI  - Do fresh osteochondral allografts successfully treat femoral condyle lesions?
AB  - BACKGROUND: Fresh osteochondral allograft transplantation is an increasingly
      common treatment option for chondral and osteochondral lesions in the knee, but
      the long-term outcome is unknown. QUESTIONS/PURPOSES: We determined (1) pain and
      function, (2) frequency and types of reoperations, (3) survivorship at a median
      of 13.5 years, and (4) predictors of osteochondral allograft failure in the
      distal femur. METHODS: We evaluated 122 patients (129 knees) who underwent
      osteochondral allograft transplantation of the femoral condyle. Mean age was 33
      years and 53% were male. Clinical evaluation included the modified Merle
      d'Aubigne-Postel (18-point), IKDC, and Knee Society function (KS-F) scores. We
      defined graft failure as revision osteochondral allografting or conversion to
      arthroplasty. We determined whether patient characteristics or attributes of the
      graft influenced failure. Minimum followup was 2.4 years (median, 13.5 years);
      91% had more than 10 years of followup. RESULTS: Mean modified Merle d'Aubigne
      Postel score improved from 12.1 to 16, mean IKDC pain score from 7.0 to 3.8, mean
      IKDC function score from 3.4 to 7.2, and mean KS-F score from 65.6 to 82.5. Sixty
      one knees (47%) underwent reoperations. Thirty-one knees (24%) failed at a mean
      of 7.2 years. Survivorship was 82% at 10 years, 74% at 15 years, and 66% at 20
      years. Age of more than 30 years at time of surgery and having two or more
      previous surgeries for the operated knee were associated with allograft failure.
      CONCLUSIONS: Followup of femoral condyle osteochondral allografting demonstrated
      durable improvement in pain and function, with graft survivorship of 82% at 10
      years.

PMID- 22961316
TI  - Efficacy and degree of bias in knee injury prevention studies: a systematic
      review of RCTs.
AB  - BACKGROUND: Knee injury prevention programs have been developed to address the
      epidemic of knee injuries in young athletes. These programs include exercises
      that focus on balance, proprioception, and neuromuscular control. Some studies
      have suggested such specialized exercise programs may reduce the risk of knee
      injury. QUESTIONS/PURPOSES: We conducted a systematic review of randomized
      controlled trials (RCTs) of knee injury prevention programs and evaluated the
      risks of bias in these studies. METHODS: We performed a systematic search using
      MEDLINE (from 1966), CINAHL (from 1982), Cochrane (CENTRAL), and EMBASE (from
      1974) in April 2011. The searches were limited to RCTs. Two reviewers
      independently assessed the internal validity of the included studies using the
      van Tulder critical appraisal tool for RCTs. Authors were contacted when internal
      validity was unclear in the methodology. Ten Level I studies (RCTs) met the
      inclusion criteria. The average risk of bias score for these studies was 7 of 11
      (range, 5-10). RESULTS: Two of the 10 studies reported a reduction in knee
      injuries. Of the three studies that provided ACL injuries as an outcome measure,
      none showed a reduction in overall ACL injury. CONCLUSIONS: Current evidence
      suggests most (eight of 10) well-designed RCTs show no difference of treatment
      benefit. Perhaps refinements of interventions may lead to a reduction in knee and
      ACL injuries in future trials. Limitations in the number and heterogeneity of
      currently published RCTs of injury prevention programs place restraints on
      quantifying intervention efficacy with a meta-analytic approach. Future research
      articles should more clearly describe the different elements of their
      methodology, consistent with the standards set forth by the CONSORT statement.

PMID- 22961317
TI  - Orthopaedic case of the month: a 72-year-old man with a painful flexion
      contracture of the left thigh.

PMID- 22961318
TI  - 50 Years ago in CORR: The use of plaster of Paris to fill defects in bone Leonard
      F. Peltier, MD CORR 1961;21:1-31.

PMID- 22961319
TI  - Letter to the editor: High rate of ceramic sandwich liner fracture.

PMID- 22961320
TI  - Letter to the editor: Peripheral triangular fibrocartilage complex tears cause
      ulnocarpal instability: a biomechanical pilot study.

PMID- 22961321
TI  - 3D hierarchically patterned tubular NiSe with nano-/microstructures for Li ion
      battery design.
AB  - Tubular nickel selenide (NiSe) crystals with hierarchical structures were
      successfully fabricated using a one-step solvothermal method in moderate
      conditions, in which ethylenediamine and ethylene glycol were used as the mixed
      solvent. The growth of hierarchical NiSe microtubes from NiSe microflakes was
      achieved without surfactants or other chemical additives by changing the reaction
      time. When the as-synthesized NiSe microtubes were employed as cathode materials
      for lithium-ion batteries, the initial discharge capacity of hierarchical NiSe
      microtubes reached 410.7 mAh g(-1).

PMID- 22961323
TI  - [Abstracts of the 110th Congress of the German Ophthalmology Society. Berlin,
      Germany. September 20-23, 2012].

PMID- 22961322
TI  - Confined placental mosaicism at chorionic villous sampling: risk factors and
      pregnancy outcome.
AB  - OBJECTIVE: This study aims to investigate the clinical relevance of confined
      placental mosaicism (CPM) detected at chorionic villous sampling (CVS) and to
      identify risk factors for this condition. METHOD: Women diagnosed with CPM
      between January 2005 and December 2009 were identified. They were matched to
      women with unremarkable CVS in a 1 : 2 ratio by study period and contacted by
      phone for interview. RESULTS: One hundred fifteen exposed and 230 unexposed women
      were selected. Baseline characteristics did not differ between the study groups
      apart from maternal body mass index, which is mildly higher in the CPM group
      (+0.6 kg/m(2), p = 0.047), and maternal age, which is higher in women with type
      III CPM (39.7 +/- 2.6 vs 37.1 +/- 3.2 years, p = 0.005). A higher frequency of
      gestational hypertension was observed in exposed women (10% vs 2%) (p = 0.003).
      Small for gestational age newborns were more frequent in women with type I CPM
      (15% vs 5%, p = 0.03). The incidence of other main complications of pregnancy
      (stillbirth, prematurity, preeclampsia and gestational diabetes mellitus) was
      similar. Neonatal complications and subsequent infant health and development did
      not also differ. CONCLUSION: Women with the diagnosis of CPM at CVS can be
      generally reassured regarding the course of pregnancy and infant health and
      development.

PMID- 22961324
TI  - The severity of duodeno-esophageal reflux influences the development of different
      histological types of esophageal cancer in a rat model.
AB  - The mechanism through which each histological type of carcinoma arises from the
      esophageal mucosa remains unknown. This study was designed to investigate whether
      there is an association between the severity of duodeno-esophageal reflux and the
      histological type of esophageal cancer. A series of 120 male Fischer rats,
      weighing ~180 g, were randomized to receive one of the following procedures:
      duodeno-forestomach reflux (DFR) with reduced exposure to duodenal contents,
      duodeno-esophageal reflux (DER) with increased exposure to duodenal contents and
      three control operations (DFR, DER control and sham). The reflux of bile was
      estimated with (99m)Tc-PMT scintigraphy. All animals were fed a standard diet
      without carcinogen. The esophageal mucosa was assessed 50 weeks after surgery for
      carcinoma. The median scanned fraction rate of duodeno-esophageal reflux was
      significantly lower for the rodents in the DFR group than those in the DER group.
      Five of 28 rodents in the DFR group and 17 of the 22 rodents in the DER group
      developed esophageal carcinoma. None of the controls developed carcinoma. The
      five rodents in the DFR group developed SCC. Of 22 esophageal carcinomas for the
      DER group, nine were SCC, 12 ADC and one was adenosquamous carcinoma. The
      fraction of esophageal SCC for the DFR group was significantly higher than that
      for the DER group, while the fraction of esophageal ADC for the DFR group was
      significantly lower than that for the DER group. These observations suggest that
      the severity of duodeno-esophageal reflux in rodents is related to the
      development of different histological types of esophageal carcinoma.

PMID- 22961325
TI  - Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder
      cancer.
AB  - miRNAs are small, non-coding RNAs that play important roles in various biological
      processes. The aims of our study were to investigate whether cell-free miRNAs can
      be measured in urine samples and might be an accurate biomarker of bladder
      cancer. Datasets of GSE20418 and GSE19717 were used for analysis, and two miRNAs,
      miR-145 and miR-200a, were selected for study. A total of 207 patients with
      primary transitional cell carcinoma of the urinary bladder and 144 healthy normal
      controls were enrolled. Using quantitative PCR, the levels of miR-145 and miR
      200a in urine were measured and compared with the clinicopathological features of
      bladder cancer. According to our experiments, cell-free miRNAs were present in
      urine and were stable. Assessment of miR-145 levels was able to distinguish
      bladder cancer patients from non-cancer controls (77.8% sensitivity and 61.1%
      specificity for NMIBC, AUC 0.729; 84.1 and 61.1% for MIBC, respectively, AUC
      0.790) and showed good correlation with grade (p=0.048). In addition, miR-200a
      was shown to be an independent predictor of NMIBC recurrence by multivariate
      analysis (OR 0.449, 95% CI 0.239-0.842, p=0.013). A higher risk of recurrence was
      observed among patients with a lower miR-200a level compared to patients with
      higher miR-200a levels (log-rank test, p=0.040). Urinary cell-free miRNAs show
      promise as noninvasive biomarkers for diagnosis and recurrence of bladder cancer.

PMID- 22961326
TI  - Computation of groundwater resources and recharge in Chithar River Basin, South
      India.
AB  - Groundwater recharge and available groundwater resources in Chithar River basin,
      Tamil Nadu, India spread over an area of 1,722 km(2) have been estimated by
      considering various hydrological, geological, and hydrogeological parameters,
      such as rainfall infiltration, drainage, geomorphic units, land use, rock types,
      depth of weathered and fractured zones, nature of soil, water level fluctuation,
      saturated thickness of aquifer, and groundwater abstraction. The digital ground
      elevation models indicate that the regional slope of the basin is towards east.
      The Proterozoic (Post-Archaean) basement of the study area consists of quartzite,
      calc-granulite, crystalline limestone, charnockite, and biotite gneiss with or
      without garnet. Three major soil types were identified namely, black cotton, deep
      red, and red sandy soils. The rainfall intensity gradually decreases from west to
      east. Groundwater occurs under water table conditions in the weathered zone and
      fluctuates between 0 and 25 m. The water table gains maximum during January after
      northeast monsoon and attains low during October. Groundwater abstraction for
      domestic/stock and irrigational needs in Chithar River basin has been estimated
      as 148.84 MCM (million m(3)). Groundwater recharge due to monsoon rainfall
      infiltration has been estimated as 170.05 MCM based on the water level rise
      during monsoon period. It is also estimated as 173.9 MCM using rainfall
      infiltration factor. An amount of 53.8 MCM of water is contributed to groundwater
      from surface water bodies. Recharge of groundwater due to return flow from
      irrigation has been computed as 147.6 MCM. The static groundwater reserve in
      Chithar River basin is estimated as 466.66 MCM and the dynamic reserve is about
      187.7 MCM. In the present scenario, the aquifer is under safe condition for
      extraction of groundwater for domestic and irrigation purposes. If the existing
      water bodies are maintained properly, the extraction rate can be increased in
      future about 10% to 15%.

PMID- 22961328
TI  - The new flora of northeastern USA: quantifying introduced plant species occupancy
      in forest ecosystems.
AB  - Introduced plant species have significant negative impacts in many ecosystems and
      are found in many forests around the world. Some factors linked to the
      distribution of introduced species include fragmentation and disturbance, native
      species richness, and climatic and physical conditions of the landscape. However,
      there are few data sources that enable the assessment of introduced species
      occupancy in native plant communities over broad regions. Vegetation data from
      1,302 forest inventory plots across 24 states in northeastern and mid-western USA
      were used to examine and compare the distribution of introduced species in
      relation to forest fragmentation across ecological provinces and forest types,
      and to examine correlations between native and introduced species richness. There
      were 305 introduced species recorded, and 66 % of all forested plots had at least
      one introduced species. Forest edge plots had higher constancy and occupancy of
      introduced species than intact forest plots, but the differences varied
      significantly among ecological provinces and, to a lesser degree, forest types.
      Weak but significant positive correlations between native and introduced species
      richness were observed most often in intact forests. Rosa multiflora was the most
      common introduced species recorded across the region, but Hieracium aurantiacum
      and Epipactus helleborine were dominant in some ecological provinces. Identifying
      regions and forest types with high and low constancies and occupation by
      introduced species can help target forest stands where management actions will be
      the most effective. Identifying seemingly benign introduced species that are more
      prevalent than realized will help focus attention on newly emerging invasives.

PMID- 22961327
TI  - Application of portable gas chromatography-photo ionization detector combined
      with headspace sampling for field analysis of benzene, toluene, ethylbenzene, and
      xylene in soils.
AB  - A method based on headspace (HS) sampling coupling with portable gas
      chromatography (GC) with photo ionization detector (PID) was developed for rapid
      determination of benzene, toluene, ethylbenzene, and xylenes (BTEX) in soils.
      Optimal conditions for HS gas sampling procedure were determined, and the
      influence of soil organic matter on the recovery of BTEX from soil was
      investigated using five representative Chinese soils. The results showed that the
      HS-portable-GC-PID method could be effectively operated at ambient temperature,
      and the addition of 15 ml of saturated NaCl solution in a 40-ml sampling vial and
      60 s of shaking time for sample solution were optimum for the HS gas sampling
      procedure. The recoveries of each BTEX in soils ranged from 87.2 to 105.1 %, with
      relative standard deviations varying from 5.3 to 7.8 %. Good linearity was
      obtained for all BTEX compounds, and the detection limits were in the 0.1 to 0.8
      MUg kg(-1) range. Soil organic matter was identified as one of the principal
      elements that affect the HS gas sampling of BTEX in soils. The HS-portable-GC-PID
      method was successfully applied for field determination of benzene and toluene in
      soils of a former chemical plant in Jilin City, northeast China. Considering its
      satisfactory repeatability and reproducibility and particular suitability to be
      operated in ambient environment, HS sampling coupling with portable GC-PID is,
      therefore, recommended to be a suitable screening tool for rapid on-site
      determination of BTEX in soils.

PMID- 22961329
TI  - Land use change and landslide characteristics analysis for community-based
      disaster mitigation.
AB  - On August 8, 2009, Typhoon Morakot brought heavy rain to Taiwan, causing numerous
      landslides and debris flows in the Taihe village area of Meishan Township, Chiayi
      County, in south-central Taiwan. In the Taihe land is primary used for
      agriculture and land use management may be a factor in the area's landslides.
      This study explores Typhoon Morakot-induced landslides and land use changes
      between 1999 and 2009 using GIS with the aid of field investigation. Spot 5
      satellite images with a resolution of 2.5 m are used for landslide interpretation
      and manually digitalized in GIS. A statistical analysis for landslide frequency
      area distribution was used to identify the landslide characteristics associated
      with different types of land use. There were 243 landslides with a total area of
      2.75 km(2) in the study area. The area is located in intrinsically fragile
      combinations of sandstone and shale. Typhoon Morakot-induced landslides show a
      power-law distribution in the study area. Landslides were mainly located in steep
      slope areas containing natural forest and in areas planted with bamboo, tea, and
      betel nut. Land covered with natural forest shows the highest landslide ratio,
      followed by bamboo, betel nut, and tea. Landslides thus show a higher ratio in
      areas planted with shallow root vegetation such as bamboo, betel nut, and tea.
      Furthermore, the degree of basin development is proportional to the landslide
      ratio. The results show that a change in vegetation cover results in a modified
      landslide area and frequency and changed land use areas have higher landslide
      ratios than non-changed. Land use management and community-based disaster
      prevention are needed in mountainous areas of Taiwan for hazard mitigation.

PMID- 22961330
TI  - [Inhibitor development after changing FVIII/IX products in patients with
      haemophilia].
AB  - The retrospective observational study surveys the relationship between
      development of inhibitors in the treatment of haemophilia patients and risk
      factors such as changing FVIII products. A total of 119 patients were included in
      this study, 198 changes of FVIII products were evaluated. RESULTS: During the
      observation period of 12 months none of the patients developed an inhibitor,
      which was temporally associated with a change of FVIII products. A frequent
      change of FVIII products didn't lead to an increase in inhibitor risk. The change
      between plasmatic and recombinant preparations could not be confirmed as a risk
      factor. Furthermore, no correlation between treatment regimens, severity, patient
      age and comorbidities of the patients could be found.

PMID- 22961331
TI  - Characteristics and sources of water-soluble ionic species associated with PM10
      particles in the ambient air of central India.
AB  - PM(10) aerosol samples were collected in Durg City, India from July 2009 to June
      2010 using an Andersen aerosol sampler and analyzed for eight water-soluble ionic
      species, namely, Na(+), NH(4) (+), K(+), Mg(2+), Ca(2+), Cl(-), NO(3) (-) and
      SO(4) (2-) by ion chromatography. The annual average concentration of PM(10)
      (253.5 +/- 99.4 MUg/m(3)) was four times higher than the Indian National Ambient
      Air Quality Standard of 60 MUg/m(3) prescribed by the Central Pollution Control
      Board, India. The three most abundant ions were SO(4) (2-), NO(3) (-), and NH(4)
      (+), with average concentrations of 8.88 +/- 4.81, 5.63 +/- 2.22, and 5.18 +/-
      1.76 MUg/m(3), respectively, and in turn accounting for 27.1 %, 16.5 %, and 15.5
      % of the total water-soluble ions analyzed. Seasonal variation was similar for
      all secondary ions i.e., SO(4) (2-), NO(3) (-), and NH(4) (+), with high
      concentrations during winter and low concentrations during monsoon. Varimax
      Rotated Component Matrix principal component analysis identified secondary
      aerosols, crustal resuspension, and coal and biomass burning as common sources of
      PM(10) in Durg City, India.

PMID- 22961332
TI  - Highly thermostable fungal cellobiohydrolase I (Cel7A) engineered using
      predictive methods.
AB  - Building on our previous efforts to generate thermostable chimeric fungal
      cellobiohydrolase I (CBH I, also known as Cel7A) cellulases by structure-guided
      recombination, we used FoldX and a 'consensus' sequence approach to identify
      individual mutations present in the five homologous parent CBH I enzymes which
      further stabilize the chimeras. Using the FoldX force field, we calculated the
      effect on DeltaG(Folding) of each candidate mutation in a number of CBH I
      structures and chose those predicted to be stabilizing in multiple structures.
      With an alignment of 41 CBH I sequences, we also used amino acid frequencies at
      each candidate position to calculate predicted effects on DeltaG(Folding). A
      combination of mutations chosen using these methods increased the T(50) of the
      most thermostable chimera by an additional 4.7 degrees C, to yield a CBH I with
      T(50) of 72.1 degrees C, which is 9.2 degrees C higher than that of the most
      stable native CBH I, from Talaromyces emersonii. This increased stability
      resulted in a 10 degrees C increase in the optimal temperature for activity, to
      65 degrees C, and a 50% increase in total sugar production from crystalline
      cellulose at the optimal temperature, compared with native T.emersonii CBH I.

PMID- 22961333
TI  - Effects of chemesthetic stimuli mixtures with barium on swallowing apnea
      duration.
AB  - OBJECTIVES/HYPOTHESIS: This study tested the hypotheses that swallowing apnea
      duration (SAD) will increase given barium versus water, chemesthetic stimuli
      (i.e., water < ethanol, acid, and carbonation) mixed with barium, age (older >
      younger), and genetic taste differences (supertasters > nontasters). STUDY
      DESIGN: Prospective group design. SETTING: University Medical Center. METHODS:
      Eighty healthy women were identified as nontasters and supertasters, equally
      comprising two age groups: 18 to 35 years and 60+ years. The KayPentax Swallowing
      Signals Lab was used to acquire SAD via nasal cannula during individually
      randomized swallows of 5 mL barium, 2.7% w/v citric acid with barium, carbonation
      with barium, and 50:50 diluted ethanol with barium. Data were analyzed using path
      analysis, with the mediator of chemesthetic perception, adjusted for repeated
      measures. RESULTS: Significant main effects of age (P = .012) and chemesthetic
      stimuli (P = .014) were found, as well as a significant interaction between
      chemesthetic stimuli and age (P = .028). Older women had a significantly longer
      SAD than younger women. Post hoc analyses revealed that barium mixed with ethanol
      elicited a significantly longer SAD than other bolus conditions, regardless of
      age group. There were no significant differences in SAD between barium and water
      conditions, and no significant effect of chemesthetic perception (P > .05).
      CONCLUSIONS: Ethanol added to barium elicited longer SAD compared to plain
      barium, but not the other chemesthetic conditions. Older women had a longer SAD
      than younger women in all conditions. These findings may influence design of
      future studies examining effects of various stimuli on SAD.

PMID- 22961334
TI  - Prevalence of diabetes and metabolic syndrome in a migrant Mixtec population,
      Baja California, Mexico.
AB  - This study was conducted to determine the prevalence and correlates of metabolic
      syndrome (MS) and diabetes among a migrant Mixtec population residing in San
      Quintin, Baja California, Mexico. A cross-sectional study utilizing data
      collected during a 2-day clinic in 2008 in a rural farming community with a high
      prevalence of Mixtec Indians. Interviews and clinical examinations were performed
      to assess sociodemographic data, medical history and anthropometric measures.
      Blood samples were obtained to measure glycated hemoglobin, fasting glucose,
      triglycerides, total cholesterol, HDL and LDL. Of the 107 patients surveyed, 56 %
      were female and mean age was 38.5 (range: 18-74, SD = 12.6) years. Overall, 41.1
      % had MS and 26.2 % had diabetes. Drinking alcohol more than once a week
      [adjusted OR (AOR) = 16.0, p = 0.008] and being literate (AOR = 0.38, p = 0.035)
      were independently associated with MS. Only female gender was significantly
      associated with diabetes (OR = 3.95, p = 0.005). The high prevalence of MS,
      diabetes and other metabolic abnormalities among migrant farm workers in San
      Quintin suggest the need for interventions to reduce the risk for these
      conditions.

PMID- 22961335
TI  - Covalent fusion inhibitors targeting HIV-1 gp41 deep pocket.
AB  - Covalent inhibitors form covalent adducts with their target, thus permanently
      inhibiting a physiological process. Peptide fusion inhibitors, such as T20
      (Fuzeon, enfuvirtide) and C34, interact with the N-terminal heptad repeat of
      human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein to form an inactive
      hetero six-helix bundle (6-HB) to prevent HIV-1 infection of host cells. A
      covalent strategy was applied to peptide fusion inhibitor design by introducing a
      thioester group into C34-like peptide. The modified peptide maintains the
      specific interaction with its target N36. After the 6-HB formation, a covalent
      bond between C- and N-peptides was formed by an inter-helical acyl transfer
      reaction, as characterized by various biophysical and biochemical methods. The
      covalent reaction between the reactive C-peptide fusion inhibitor and its N
      peptide target is highly selective, and the reaction greatly increases the
      thermostability of the 6-HB. The modified peptide maintains high potency against
      HIV-1-mediated cell-cell fusion and infection.

PMID- 22961336
TI  - Evidence for a vast peptide overlap between West Nile virus and human proteomes.
AB  - The primary amino acid sequence of West Nile virus (WNV) polyprotein, GenBank
      accession number M12294, was analyzed by computional biology. WNV is a mosquito
      borne neurotropic flavivirus that has emerged globally as a significant cause of
      viral encephalitis in humans. Using pentapeptides as scanning units and the
      perfect peptide match program from PIR International Protein Sequence Database,
      we compared the WNV polyprotein and the human proteome. WNV polyprotein showed
      significant sequence similarities to a number of human proteins. Several of these
      proteins are involved in embryogenesis, neurite outgrowth, cortical neuron
      branching, formation of mature synapses, semaphorin interactions, and voltage
      dependent L-type calcium channel subunits. The biocomputional study suggest that
      common amino acid segments might represent a potential platform for further
      studies on the neurological pathophysiology of WNV infections. 

PMID- 22961337
TI  - Rationally-designed fluorescent lysine riboswitch probes.
AB  - Two fluorescent lysine amide analogs, in which the carboxyl end of lysine was
      covalently attached to dansyl or NBD groups through an ethylene glycol-based
      linker, were rationally designed and synthesized. Both probes showed high binding
      affinity to the lysine riboswitch in vitro and their fluorescence intensities
      decreased by riboswitch binding.

PMID- 22961338
TI  - Viral evolution: Accordion adaptations go viral.

PMID- 22961339
TI  - Plant pathogens: Oomycete kinase blights potatoes.

PMID- 22961340
TI  - Metagenomics with guts.

PMID- 22961342
TI  - Prevalence and causes of visual impairment in elderly Amis aborigines in Eastern
      Taiwan (the Amis Eye Study).
AB  - PURPOSE: To investigate the prevalence and causes of visual impairment in elderly
      Amis aborigines in Eastern Taiwan. METHODS: Population-based cross-sectional
      study of visual impairment of elderly Amis (65 years of age or older). We
      conducted ocular examinations on 2,316 participants, which represent 61.2 % of
      the elderly population. We used WHO criteria to identify visual impaired
      subjects, and the causes were analyzed. RESULTS: Ninety-four subjects were
      identified with low vision and nineteen were blind. The prevalence of low vision
      was 4.06 % (95 % confidence interval, 3.26, 4.56 %); that of blindness was 0.82 %
      (95 % confidence interval, 0.45, 1.19 %). Cataracts (47.79 %) were the main cause
      of visual impairment, followed by age-related macular degeneration (15.93 %),
      corneal opacity (7.96 %), optic neuropathy (7.96 %), diabetic retinopathy (5.31
      %), and retinitis pigmentosa (2.65 %). Glaucoma was a minor cause of visual
      impairment. There were no significant gender differences in the prevalence and
      specific causes of visual impairment. CONCLUSION: The prevalence of treatable
      causes of vision impairment, for example cataracts and corneal opacity, is high
      among the elderly Amis aborigines. They would, therefore, benefit from a more
      aggressive and in-depth eye-care program as a blindness-prevention strategy.

PMID- 22961341
TI  - Understanding and learning from the success of prophylactic human papillomavirus
      vaccines.
AB  - An estimated 5% of human cancers are caused by human papillomavirus (HPV)
      infections, and most of these cancers are of the cervix. Two prophylactic HPV
      vaccines that target the two most oncogenic virus types, HPV16 and HPV18, are now
      commercially available. In controlled clinical trials, the vaccines proved to be
      effective at preventing incident anogenital infection and the associated
      neoplastic disease that is induced by these virus types. Here, we highlight the
      specific aspects of HPV biology and vaccine composition that are likely to
      contribute to the efficacy of these vaccines, and we discuss how these particular
      features might or might not be relevant for the development of effective vaccines
      against other sexually transmitted viruses such as HIV and herpes simplex virus
      (HSV).

PMID- 22961343
TI  - Vasodilatory effects of antivascular endothelium growth factor (VEGF) antibody,
      corticosteroid, and nitric oxide on the posterior ciliary arteries.
AB  - PURPOSE: The purpose of this study was to determine whether an antivascular
      endothelium growth factor (VEGF) antibody, a corticosteroid, and sodium
      nitroprusside (SNP) [a nitric oxide (NO) donor] are possible treatment agents for
      nonarteritic ischemic optic neuropathy (NAION) by clarifying their effects on
      high-K (potassium) solution-induced contraction in isolated rabbit and human
      posterior ciliary arteries (PCA). METHODS: Vascular ring segments were cut from
      the distal section of the PCA and mounted in a double-myograph system. After
      obtaining the maximal contraction following the administration of high-K
      solution, bevacizumab as an anti-VEGF antibody, methylprednisolone as a
      corticosteroid, and SNP were administered separately. When a vasodilatory effect
      was observed, carboxy-PTIO (a NO scavenger) or L-NAME (a NO synthase inhibitor)
      was administered. RESULTS: Bevacizumab did not relax either the rabbit or the
      human PCA, whereas methylprednisolone relaxed both. Neither carboxy-PTIO nor L
      NAME inhibited methylprednisolone-induced relaxation. SNP relaxed the rabbit PCA.
      Carboxy-PTIO inhibited SNP-induced relaxation, but L-NAME did not. In the human
      PCA, the vasodilatory effect of SNP was present, but weaker than in the rabbit
      PCA. CONCLUSIONS: A corticosteroid has NO-independent vasodilatory effects.
      Exogenous NO has a weak dilating effect in the human PCA. Therefore,
      corticosteroid could be effective for the treatment of NAION.

PMID- 22961344
TI  - GATA5 loss-of-function mutation responsible for the congenital ventriculoseptal
      defect.
AB  - The ventriculoseptal defect (VSD) is the most common form of congenital heart
      disease and a leading noninfectious cause of infant mortality. Growing evidence
      demonstrates that genetic defects are associated with congenital VSD.
      Nevertheless, VSD is genetically heterogeneous, and the molecular basis for VSD
      in an overwhelming majority of patients remains unknown. In this study, the whole
      coding region of GATA5, a gene encoding a zinc finger transcription factor
      crucial for normal cardiogenesis, was sequenced in 120 unrelated patients with
      VSD. The available relatives of the patient harboring the identified mutation and
      200 unrelated individuals used as controls were subsequently genotyped. The
      causative potential of a sequence variation was evaluated by MutationTaster, and
      the functional effect of the mutation was characterized using a luciferase
      reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.L199V,
      was identified in a patient with VSD, which was absent in 400 control
      chromosomes. Genetic analysis of the mutation carrier's available family members
      showed that the substitution co-segregated with VSD transmitted in an autosomal
      dominant pattern. The p.L199V variation was automatically predicted to be disease
      causing, and the functional analysis showed that the GATA5 p.L199V mutant protein
      was associated with significantly reduced transcriptional activation compared
      with its wild-type counterpart. To the best of the authors' knowledge, this is
      the first report on the link of functionally compromised GATA5 to human VSD,
      suggesting potential implications for the early prophylaxis and personalized
      treatment of VSD.

PMID- 22961345
TI  - Femoral arterial thrombosis after cardiac catheterization in infancy: impact of
      Doppler ultrasound for diagnosis.
AB  - Femoral arterial thrombosis (FAT) is a nonnegligible complication after cardiac
      catheterization (CC) in infancy. The aim of this study was to evaluate the impact
      of Doppler ultrasound (US) for diagnostic work-up after catheterization. We
      compared standard follow-up (FU) without Doppler US by relying on clinical signs
      of FAT with advanced FU using Doppler US of the femoral vessels. Between January
      and December 2009, we evaluated the rate of FAT in infants <12 months of age
      using a multicenter, prospective observational survey. We analysed 171 patients
      [mean age 4.1 +/- 3.3 (SD) months; mean body weight 5.3 +/- 1.8 kg] from 6
      participating centres. The mean duration of catheter studies was 57.7 +/- 38.0
      min. The overall rate of FAT based on clinical diagnosis was 4.7% and was
      comparable in both groups [3.4% undergoing standard FU vs. 7.4% undergoing
      advanced FU (p = 0.15)]. However, the overall rate of thrombosis as screened by
      Doppler US was greater at 7.1 %, especially in patients after advanced FU [18.5%
      advanced vs. standard FU 1.7% (p < 0.01)]. In conclusion, FAT remains a relevant
      and underestimated complication after catheterization in young infants when
      relying only on clinical signs of FAT. Therefore, to start effective treatment as
      soon as possible, we recommend Doppler US to be performed the day after CC.

PMID- 22961346
TI  - Hypoplastic left heart syndrome and pulmonary veno-occlusive disease in an
      infant.
AB  - This report describes an infant with heterotaxy syndrome and severe hypoplasia of
      the left heart who presented with profound cyanosis at birth despite a large
      patent ductus arteriosus. Pulmonary venous return was difficult to demonstrate by
      echocardiography. Angiography showed total anomalous pulmonary venous return via
      a plexus that drained through the paravertebral veins and bilateral superior vena
      cavae. Autopsy confirmed these findings, and histopathology demonstrated severe
      occlusive changes within the pulmonary veins. 

PMID- 22961347
TI  - The Munich Triathlon Heart Study: ventricular function, myocardial velocities,
      and two-dimensional strain in healthy children before and after endurance stress.
AB  - Intense exercise has been shown to have negative effects on systolic and
      diastolic ventricular function in adults. Very little is known about the normal
      reaction of the growing heart to endurance stress. For this study, 26 healthy
      children (18 males) with a mean age of 12.61 years (range, 7.92-16.42 years) took
      part in an age-adapted triathlon circuit. The athletes were investigated by two
      dimensional (2D) echocardiographic/speckle tracking, M-mode, pulse-wave Doppler,
      color Doppler, and color-coded tissue Doppler at 2-4 weeks before and immediately
      after the race. After the competition, cardiac output increased, mediated by an
      increase in heart rate and not by an elevated preload, according the Frank
      Starling mechanism. Two-dimensional speckle tracking showed a reduced
      longitudinal strain in the right and left ventricles and additionally reduced
      circumferential strain in the left ventricle. The late diastolic inflow
      velocities were increased in both ventricles, indicating reduced diastolic
      function due to an impairment of myocardial relaxation. Immediately after
      endurance exercise, systolic and diastolic functions were attenuated in children
      and adolescents. In contrast to adult studies, this study could show a heart rate
      mediated increase in cardiac output. The sequelae of these alterations are
      unclear, and the growing heart especially may be more susceptible to myocardial
      damage caused by intense endurance stress.

PMID- 22961348
TI  - Dmp53 is sequestered to nuclear bodies in spermatogonia of Drosophila
      melanogaster.
AB  - p53 family members have been implicated in regulation of genomic integrity and
      apoptosis in a variety of tissues. The Drosophila family member, Dmp53, primarily
      functions to regulate apoptosis in developing and regenerating tissues but loss
      of function mutants are viable and fertile. Dmp53 exhibits a striking expression
      pattern in the male germline with high levels found in nuclear bodies in pre
      meiotic germ cells. The localisation of Dmp53 to nuclear bodies is dependent upon
      Dmp53 complexes being able to bind DNA, and although dmp53 mutants do not affect
      germline stem cell (GSC) maintenance or differentiation, GSCs are sensitive to
      overexpression of Dmp53 but maturing spermatogonia are not. Dmp53 thus has
      differential effects depending upon the stage of male germline maturation.

PMID- 22961349
TI  - [Central nervous system complications in patients undergoing cytotoxic
      chemotherapy and targeted therapies].
AB  - Anti-cancer treatments (cytotoxic chemotherapies, targeted therapies and
      hormonotherapies) are known to induce early and delayed neurological toxicities.
      Acute encephalopathies and posterior reversible encephalopathies are better known
      and described, physiopathological hypotheses are emerging. It is difficult to
      discriminate what drug is causing the symptoms in patients treated with multiple
      cytotoxic drugs. Methotrexate and ifosfamide are responsible for acute
      encephalopathies. L-asparaginase and methotrexate or targeted therapies may
      induce cerebrovascular complications. As life expectancy increases and more
      complex regimen including innovative targeted therapies are developed, new
      toxicity profiles can be expected. To be able to provide an early diagnosis,
      prevention, and treatment (when existing) of these pathologies remains a
      tremendous challenge that would allow a good quality of life with social and
      professional life after their cancer is cured.

PMID- 22961350
TI  - Cardiac arrest in the toilet: clinical characteristics and resuscitation
      profiles.
AB  - OBJECTIVES: The great majority of non-traumatic cardiac arrests (CA) occur at
      home. The toilet is a closed and private room where CA occurs frequently.
      However, due to the feelings of privacy that are associated with this room, the
      circumstances and causes of CA in the toilet have rarely been investigated.
      METHODS: A retrospective study was conducted to clarify clinical characteristics
      and resuscitation profiles of patients sustaining CA in the toilet. RESULTS:
      Among 907 CA patients treated during a 4-year period, 101 (11 %) sustained CA in
      the toilet. While the collapse was witnessed in only 10 % of these patients,
      return of spontaneous circulation (ROSC) was achieved in 41 %. However, the long
      term survival rate was 1 %. Multivariate regression analysis revealed that a
      history of cardiac diseases was predictive of CA in the toilet (odds ratio 3.045;
      95 % confidence interval 1.756-5.282) but that there was no correlation with
      advanced age. The frequency of CA in the toilet may be influenced moderately by
      seasonal/circadian variations. The 101 patients were classified into four
      subgroups according to mode of discovery of CA. The frequency of ROSC was highest
      in those who collapsed in the presence of caregivers and lowest in those whose
      collapse were discovered later by family members being worried that the patient
      stayed in the toilet "too long." Imaging studies revealed life-threatening extra
      cardiac lesions responsible for CA, such as subarachnoid hemorrhage and aortic
      dissection, in 23 % of the patient cohort. CONCLUSIONS: The rarity of long-term
      survival among individuals sustaining CA in the toilet is mainly due to the delay
      in discovering the individual who collapsed. Although a history of cardiac
      diseases is a risk factor, predicting who may sustain CA in the toilet remains
      difficult due to etiological heterogeneity.

PMID- 22961351
TI  - Association of genotypes of carcinogen-metabolizing enzymes and smoking status
      with bladder cancer in a Japanese population.
AB  - OBJECTIVES: Arylamines are considered to be the primary causative agent of
      bladder cancer in tobacco smokers. To test the hypothesis that variation in the
      genes that metabolize tobacco carcinogens contribute to bladder cancer, we
      examined the effects of single nucleotide polymorphisms in the genes of four key
      enzymes: cytochrome P450 1A2, N-acetyltransferase (NAT) 2, sulfotransferase 1A1,
      and UDP-glucuronosyltransferase (UGT) 2B7. METHODS: In this study, 282 Japanese
      patients with transitional cell carcinoma, the most common bladder cancer, and
      257 healthy controls were surveyed and compared for frequencies of the genotypes
      of the four enzymes. Genotypes were determined using PCR-restriction fragment
      length polymorphism and TaqMan assays. Smoking information was collected by
      personal interview. Logistic regression analysis and the chi-square test were
      employed as statistical methods. RESULTS: The NAT2 slow genotype was
      significantly associated with the risk of bladder cancer [odds ratio (OR) 3.41,
      95 % confidence interval (95 % CI) 1.68-6.87; p < 0.05). The NAT2 slow genotype
      also significantly increased the risk of bladder cancer in heavy smokers (OR
      8.57, 95 % CI 1.82-40.25; p < 0.05). Among the different combinations of the four
      enzyme genotypes, the highest OR (4.20; 95 % CI 1.34-13.14; p < 0.05) was
      obtained with the NAT2 slow genotype when present in combination with the UGT2B7
      *2/*2 or *1/*2 genotype. CONCLUSIONS: Our results suggest that individuals with
      different genotypes for the enzymes involved in metabolizing carcinogenic
      arylamines have a different risk of developing bladder cancer. In particularly,
      the combination of the NAT2 slow genotype with UGT2B7 *1/*2 or *2/*2 genotype is
      a high risk factor for bladder cancer.

PMID- 22961352
TI  - Screened butanol-tolerant Enterococcus faecium capable of butanol production.
AB  - Due to the complex mechanisms involved in butanol-induced stress response,
      butanol tolerance phenotype is difficult to engineer even in microorganisms with
      well-defined genetic backgrounds. We therefore aimed to isolate butanol-tolerant
      microorganisms from environmental samples as potential alternative hosts for
      butanol production. Soil samples collected were subjected to butanol stress. A
      microbial strain capable of 2.5-3 % (w/v) butanol tolerance was isolated and
      identified as Enterococcus faecium by 16S rDNA analysis. The isolate grew readily
      under both aerobic and anaerobic conditions and was capable of producing butanol
      anaerobically. In comparison with the obligate anaerobe Clostridium
      acetobutylicum, the growth under both aerobic and anaerobic conditions of the
      isolated strain, together with no detection of butyrate and lack of two-phase
      fermentation suggests different metabolic networks from the obligate anaerobe C.
      acetobutylicum. Under anaerobic condition, butanol reached up to 0.4 gl(-1) in a
      batch culture without heterologous introduction of butanol biosynthetic pathway.
      Besides butanol tolerance, the isolated E. faecium IB1 showed high tolerance to
      10 % (w/v) ethanol and 3 % (w/v) isobutanol. With distinct features including
      high butanol tolerance and natural butanol production, the isolated E. faecium
      IB1 with minimum metabolic engineering can be explored as a potential host for
      butanol production.

PMID- 22961353
TI  - Sodium current inhibition by nanosecond pulsed electric field (nsPEF)--fact or
      artifact?
AB  - In two recent publications in Bioelectromagnetics it has been demonstrated that
      the voltage-gated sodium current (I(Na)) is inhibited in response to a nanosecond
      pulsed electric field (nsPEF). At the same time, there was an increase in a non
      inactivating "leak" current (I(leak)), which was attributed to the formation of
      nanoelectropores or larger pores in the plasma membrane. We demonstrate that the
      increase in I(leak), in combination with a residual series resistance, leads to
      an error in the holding potential in the patch clamp experiments and an
      unanticipated inactivation of the sodium channels. We conclude that the observed
      inhibition of I(Na) may be largely, if not fully, artifactual.

PMID- 22961354
TI  - Selective palladation of a large (32 ring atom) macrocyclic ligand at a bis(N
      heterocyclic carbene) coordination pocket through transmetallation of the
      corresponding mercury(II) derivative.
AB  - Treatment of N(2),N(6)-bis(6-acrylamidopyridin-2-yl)pyridine-2,6-dicarboxamide
      with benzimidazole gives the acyclic aza-Michael addition product N(2),N(6)-bis(6
      (3-(1H-benzo[d]imidazol-1-yl)propanamido)pyridin-2-yl)pyridine-2,6-dicarboxamide
      (2). The macrocycle N(1),N(7)-pyridine-2,6-dimethyl-N(2),N(6)-bis(6-(3-(1H
      benzo[d]imidazol-1-yl)propanamido)pyridin-2-yl)pyridine-2,6-dicarboxamide
      dibromide ([H(2)L(2)]Br(2)) is formed through the double alkylation of 2 with 2,6
      bis(bromomethyl)pyridine. The imidazole analogues of 2 and [H(2)L(2)]Br(2) (1 and
      [H(2)L(1)]Br(2), respectively) have also been prepared. Mercuration of the two
      benzimidazolium groups in [H(2)L(2)]Br(2) with mercury(II) acetate in the
      presence of [N(CH(3))(4)](2)[HgBr(4)] proceeds to give [HgL(2)][HgBr(4)] in good
      yield. The ability of [HgL(2)][HgBr(4)] to readily partake in transmetallation
      reactions is demonstrated by the reaction that occurs with PdCl(2)(COD) to form
      [PdClL(2)][PF(6)]. The structures of 2, [HgL(2)][HgBr(4)] and [PdClL(2)][PF(6)]
      have been determined.

PMID- 22961355
TI  - Benign epilepsy of childhood with centro-temporal spikes (BECTS) versus migraine:
      a neuropsychological assessment.
AB  - PURPOSE: Epilepsy and migraine frequently show a clinical overlap. An increase in
      number of electroencephalographic abnormalities, such as centro-temporal spikes
      (CTS), may be observed in patients suffering from migraine, epileptic
      abnormalities that are typically in benign epilepsy of childhood with CTS
      (BECTS). The aim of this study is to better define the role of CTS in children
      with migraine compared to children with BECTS, in relation with their
      neuropsychological profile. METHODS: Thirty-two children were enrolled and
      divided into three groups on the basis of their diagnosis: 16 children (eight
      males and eight females, aged 12.3 +/- 2.58 years) affected by BECTS, 8 patients
      (four males and four females, aged 11.8 +/- 3.47 years) affected by BECTS and
      migraine, and 8 children (four males and four females, aged 13.5 +/- 1.79 years)
      affected by migraine showing CTS abnormalities. A cognitive and
      neuropsychological assessment was performed, using Wechsler Intelligence Scale
      for Children-third edition and NEPSY II, in all patients. RESULTS AND
      CONCLUSIONS: A similar neuropsychological impairment was found in patients
      affected by BECTS and in those affected by BECTS and migraine; a significant
      deficit in short- and long-term verbal memory was evident in patients affected by
      migraine and CTS. CTS in patients with migraine can influence the
      neuropsychological tests, with a possible negative impact on language and
      learning development.

PMID- 22961356
TI  - Spinal cord ependymomas in children and adolescents.
AB  - BACKGROUND: Spinal cord ependymomas are very rare among children and adolescents.
      Due to their rarity, our current knowledge of these tumors is based on case
      reports and few retrospective case series. METHODS: The present review summarizes
      the currently available literature on childhood spinal cord ependymomas. RESULTS:
      Although overall survival rates are favorable, relapse incidence is high,
      particularly in myxopapillary ependymomas. Since long-term follow-up data are
      provided in a limited number of studies only, the true relapse incidence is
      unknown. Maximal safe radical surgery is the backbone of treatment for children
      with spinal cord ependymomas, but the impact of adjuvant treatment on progression
      and survival is still unclear. Presently, the decision to initiate non-surgical
      treatment depends primarily on the WHO grade of the tumor and the extent of
      resection. In terms of the known side effects, early radiotherapy should be
      avoided in children with WHO grade II spinal cord ependymomas irrespective of the
      extent of resection but is indicated in anaplastic spinal cord ependymomas both
      after complete and incomplete resection. The high relapse incidence in
      myxopapillary ependymomas argue for the use of early radiotherapy, but its
      definitive impact on progression has to be proven in larger series. Close
      surveillance is important due to the high recurrence rate in all patients with
      spinal cord ependymomas. CONCLUSION: Prospective collection of both clinical and
      molecular data from a greater number of patients with spinal cord ependymomas
      within an international collaboration is the prerequisite to establish
      standardized management guidelines for these rare CNS tumors.

PMID- 22961358
TI  - Massive cystic dilatation within a tethered filum terminale causing cauda equina
      compression and mimicking syringomyelia in a young adult patient.
AB  - BACKGROUND: The ventriculus terminalis (VT) is formed during early embryonic
      development of the spinal cord and can only be identified histologically in both
      children and adults. Cystic dilatation of the VT can be seen in young children,
      but it rarely persists through adulthood. CLINICAL CASE: We describe a 27-year
      old female with paraparesis secondary to a massive and tethered cystic dilatation
      of the VT mimicking syringomyelia. Symptoms appearing in early childhood were
      ignored, probably leading to the much prominent presentation in early adulthood.
      The preoperative presentation and surgical treatment are discussed in relation to
      childhood history. CONCLUSIONS: Although extremely rare, symptomatic dilatation
      of the VT can be seen in young adults, usually with previous manifestations in
      early childhood. This entity should be considered while treating tethered cord
      spectrum.

PMID- 22961357
TI  - The intracranial arachnoid mater : a comprehensive review of its history,
      anatomy, imaging, and pathology.
AB  - INTRODUCTION: The arachnoid mater is a delicate and avascular layer that lies in
      direct contact with the dura and is separated from the pia mater by the
      cerebrospinal fluid-filled subarachnoid space. The subarachnoid space is divided
      into cisterns named according to surrounding brain structures. METHODS: The
      medical literature on this meningeal layer was reviewed in regard to historical
      aspects, etymology, embryology, histology, and anatomy with special emphasis on
      the arachnoid cisterns. Cerebrospinal fluid dynamics are discussed along with a
      section devoted to arachnoid cysts. CONCLUSION: Knowledge on the arachnoid mater
      and cerebrospinal fluid dynamics has evolved over time and is of great
      significance to the neurosurgeon in clinical practice.

PMID- 22961359
TI  - Multimodal MR imaging findings of a congenital glioblastoma multiforme.

PMID- 22961360
TI  - Severe spinal cord injury in craniocervical dislocation. Case-based update.
AB  - BACKGROUND: Craniocervical distraction injuries, including atlanto-axial
      dislocation (AAD) and atlanto-ocipital dislocation (AOD), are often associated
      with severe spinal cord involvement with high morbidity and mortality rates. Many
      patients with these injuries die at the accident scene, but advances in emergency
      resuscitation and transport permit that many patients arrive alive to hospitals.
      DISCUSSION: Children with craniocervical distraction injuries usually present
      with a severe cranioencephalic traumatism that is the most relevant lesion at
      admission. After resuscitation and hemodynamic stabilization, the spinal cord
      damage appears as the main lesion. Apnea and quadriparesis, or quadriplegia, are
      usually present at the onset. Early diagnosis and management perhaps decrease
      life-threatening manifestations of the spinal lesion. But even so, the primary
      spinal cord insult is often irreversible and precludes obtaining a satisfactory
      functional outcome. PATIENTS AND METHODS: We report the findings of four children
      with craniocervical distraction injuries (AOD and AAD) who presented with severe
      spinal cord damage. All patients were admitted with respiratory distress or apnea
      together with significant brain injuries. The medical records pertaining to these
      patients are summarized in regard to clinical features, management, and outcome.
      CONCLUSIONS: In spite of timely and aggressive management, craniocervical
      injuries with spinal cord involvement continue to have a dismal prognosis.
      Outcome is closely related to the severity of the initial brain and spinal cord
      damage and is nearly always fatal in cases of complete spinal cord transection.
      Priority should be given to life-threatening complications. Ethic issues on
      indications for surgery deserve a detailed discussion with the children's
      parents.

PMID- 22961361
TI  - Risk of germ cell testicular cancer according to origin: a migrant cohort study
      in 1,100,000 Israeli men.
AB  - Testicular cancer incidence is highest among men of northern European ancestry
      and lowest among men of Asian/African descent. We conducted a large-scale migrant
      cohort study to assess origin and migrant generation as predictors of testicular
      germ cell tumors (TGCTs), controlling for possible confounders. Data on 1,092,373
      Jewish Israeli males, who underwent a general health examination prior to
      compulsory military service at ages 16-19 between the years 1967-2005, were
      linked to Israel National Cancer Registry to obtain incident TGCTs up to 2006.
      Cox proportional hazards was used to model time to event. Overall, 1,001 incident
      cases (534 seminoma and 467 nonseminoma) were detected during 19.2 million person
      years of follow-up. Origin was a strong independent predictor of TGCTs with
      remarkably low incidence for North African-born (HR = 0.10, 95% CI: 0.04-0.21)
      and Asian-born (HR = 0.35, 0.20-0.62), while intermediate for Israeli-born of
      North African origin (HR = 0.48, 0.40-0.58) and Asian origin (HR = 0.56, 0.47
      0.66), compared to European origin. A comparison of Israeli born of North African
      and Asian origin with North African and Asian-born yielded a HR of 2.31 (1.36
      3.93). Significant risk factors controlled for were year of birth, years of
      education and height. Findings persisted when analyses were stratified by
      histologic subtypes of TGCTs. The findings of lower rates of TGCTs among men born
      in North Africa and Asia compared to European ancestry, but a steep increase in
      next generation migrants, particularly among the Israeli-born migrants from North
      Africa, provide clues to direct further research on the role of modern lifestyle
      and environment in the etiology of TGCTs.

PMID- 22961362
TI  - Promoting a trained MCH epidemiology workforce in state public health agencies
      through strategies developed from continued partnerships.

PMID- 22961363
TI  - Influence of season and plant species on the abundance and diversity of sulfate
      reducing bacteria and ammonia oxidizing bacteria in constructed wetland
      microcosms.
AB  - Constructed wetlands offer an effective means for treatment of wastewater from a
      variety of sources. An understanding of the microbial ecology controlling
      nitrogen, carbon and sulfur cycles in constructed wetlands has been identified as
      the greatest gap for optimizing performance of these promising treatment systems.
      It is suspected that operational factors such as plant types and hydraulic
      operation influence the subsurface wetland environment, especially redox, and
      that the observed variation in effluent quality is due to shifts in the microbial
      populations and/or their activity. This study investigated the biofilm associated
      sulfate reducing bacteria and ammonia oxidizing bacteria (using the dsrB and amoA
      genes, respectively) by examining a variety of surfaces within a model wetland
      (gravel, thick roots, fine roots, effluent), and the changes in activity (gene
      abundance) of these functional groups as influenced by plant species and season.
      Molecular techniques were used including quantitative PCR and denaturing gradient
      gel electrophoresis (DGGE), both with and without propidium monoazide (PMA)
      treatment. PMA treatment is a method for excluding from further analysis those
      cells with compromised membranes. Rigorous statistical analysis showed an
      interaction between the abundance of these two functional groups with the type of
      plant and season (p < 0.05). The richness of the sulfate reducing bacterial
      community, as indicated by DGGE profiles, increased in planted vs. unplanted
      microcosms. For ammonia oxidizing bacteria, season had the greatest impact on
      gene abundance and diversity (higher in summer than in winter). Overall, the
      primary influence of plant presence is believed to be related to root oxygen loss
      and its effect on rhizosphere redox.

PMID- 22961364
TI  - Virus community dynamics in the conifer pathogenic fungus Heterobasidion
      parviporum following an artificial introduction of a partitivirus.
AB  - Viruses infecting the conifer pathogenic fungus Heterobasidion annosum sensu lato
      are intracellular and spread via anastomosis contacts. In the laboratory, these
      viruses transmit readily even between somatically incompatible isolates, but
      their dispersal capacity in natural conditions has not been previously studied.
      We introduced a mycovirus to a heavily diseased forest site by inoculating Norway
      spruce stumps with heartrot decay using a mycelial suspension of Heterobasidion
      parviporum strain RT3.49C hosting the partitivirus strain HetRV4-pa1. The
      Heterobasidion population at the sample plot was screened for mycoviruses prior
      to and after the inoculation. Based on sequence analysis, the resident H.
      parviporum strains harbored six different strains of the virus species
      Heterobasidion RNA virus 6 (HetRV6) and one strain of HetRV4 prior to the
      inoculation. After three growth seasons, the inoculated H. parviporum host strain
      was not detected, but the introduced virus had infected two resident H.
      parviporum genets. The presence of a preexisting HetRV6 infection did not hinder
      spread of the introduced partitivirus but resulted in coinfections instead. The
      resident HetRV6 virus population seemed to be highly stable during the incubation
      period, while the single indigenous HetRV4 infection was not detected after the
      inoculation. In laboratory infection experiments, the introduced virus could be
      transmitted successfully into all of the resident H. parviporum genets. This
      study shows for the first time transmission of a Heterobasidion virus between
      somatically incompatible hosts in natural conditions.

PMID- 22961365
TI  - Elevated atmospheric CO2 impacts abundance and diversity of nitrogen cycling
      functional genes in soil.
AB  - The concentration of CO(2) in the Earth's atmosphere has increased over the last
      century. Although this increase is unlikely to have direct effects on soil
      microbial communities, increased atmospheric CO(2) may impact soil ecosystems
      indirectly through plant responses. This study tested the hypothesis that
      exposure of plants to elevated CO(2) would impact soil microorganisms responsible
      for key nitrogen cycling processes, specifically denitrification and
      nitrification. We grew trembling aspen (Populus tremuloides) trees in outdoor
      chambers under ambient (360 ppm) or elevated (720 ppm) levels of CO(2) for 5
      years and analyzed the microbial communities in the soils below the trees using
      quantitative polymerase chain reaction and clone library sequencing targeting the
      nitrite reductase (nirK) and ammonia monooxygenase (amoA) genes. We observed a
      more than twofold increase in copy numbers of nirK and a decrease in nirK
      diversity with CO(2) enrichment, with an increased predominance of Bradyrhizobia
      like nirK sequences. We suggest that this dramatic increase in nirK-containing
      bacteria may have contributed to the significant loss of soil N in the CO(2)
      treated chambers. Elevated CO(2) also resulted in a significant decrease in copy
      numbers of bacterial amoA, but no change in archaeal amoA copy numbers. The
      decrease in abundance of bacterial amoA was likely a result of the loss of soil N
      in the CO(2)-treated chambers, while the lack of response for archaeal amoA
      supports the hypothesis that physiological differences in these two groups of
      ammonia oxidizers may enable them to occupy distinct ecological niches and
      respond differently to environmental change.

PMID- 22961366
TI  - Carboplatin treatment of antiestrogen-resistant breast cancer cells.
AB  - Antiestrogen resistance is a major clinical problem in current breast cancer
      treatment. Therefore, biomarkers and new treatment options for antiestrogen
      resistant breast cancer are needed. In this study, we investigated whether
      antiestrogen-resistant breast cancer cell lines have increased sensitivity to
      carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2
      expression levels have a potential value as marker for increased carboplatin
      sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant,
      and two out of four cell lines resistant to the antiestrogen tamoxifen, were more
      sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This
      indicates that carboplatin may be an advantageous treatment in antiestrogen
      resistant breast cancer; however, a marker for increased sensitivity would be
      needed. Low Bcl-2 expression was correlated with increased carboplatin response
      in the tamoxifen-resistant cell line MCF-7/TAMR-1 and overexpression of Bcl-2 in
      this cell line resulted in significantly reduced carboplatin sensitivity,
      confirming the anti-apoptotic role of Bcl-2. However, neither Bcl-2 expression
      alone, nor Bcl-2 in combination with Bcl-xL and Bax, could explain the observed
      responses to carboplatin in all tamoxifen-resistant cell lines, indicating that
      more markers are needed to predict the response to carboplatin in tamoxifen
      resistant breast cancer.

PMID- 22961367
TI  - Exploring the clinical value and implications of routine pathological examination
      of septoplasty specimens.
AB  - OBJECTIVES/HYPOTHESIS: During septoplasty, otherwise normal cartilage and bone
      are removed and routinely submitted for pathologic examination. According to the
      College of American Pathologists, however, the examination of bone and cartilage
      from septoplasty and rhinoplasty may be left to the pathologist's discretion. We
      explored the processing of tissues removed during septoplasty, examining the
      clinical value and implications of current practices. STUDY DESIGN: Retrospective
      chart review. METHODS: Our database was searched for septoplasty (CPT code 30520)
      procedures performed specifically for the indication of nasal obstruction.
      RESULTS: Five hundred sixteen consecutive cases from 15 surgeons spanning a 2
      year period were identified. In the majority of cases, septal tissues removed
      during surgery were submitted to pathology. The majority of cases (>90%) involved
      septoplasty performed in conjunction with another procedure, most commonly
      addressing the inferior turbinates. All septal specimens received gross
      examination by a pathologist, and a smaller fraction were also examined
      histologically. Gross findings included the qualitative appearance of the
      specimen and dimensional measurements of bone and cartilage fragments. No
      abnormalities were identified (by gross or histologic examination) in any of the
      specimens. Associated costs included specimen handling, storage, and pathology
      fees. CONCLUSIONS: In our health care system, it is common practice to submit
      tissues removed during septoplasty for pathologic examination. This study
      demonstrates that routine evaluation of septal tissues following surgery for
      obstruction has no clinical value whatsoever, and is associated with direct and
      indirect costs. Given the current health care climate, this practice should be
      further scrutinized and reconsidered.

PMID- 22961368
TI  - The earliest evidence of millet as a staple crop: New light on neolithic foodways
      in North China.
AB  - There is a growing body of archaeobotanical evidence for the harvesting of millet
      in Eurasia prior to 5,000 cal. BC. Yet direct evidence for the extent of millet
      consumption in this time period is rare. This contradiction may be due to millet
      crops making only a minor contribution to the diet before 5,000 BC. In this
      article, drawing from recent excavations in North China, we present evidence for
      millet crops making a substantial contribution to human and animal diets in
      periods, which correspond chronologically with the time depth of the
      archaeobotanical record. We infer that in eastern Inner Mongolia, human adoption
      of millets, which may or may be not related to substantial agriculture, happened
      at the Early Neolithic, with direct dates between 5,800 and 5,300 cal. BC.

PMID- 22961369
TI  - Malaria infection and feather growth rate predict reproductive success in house
      martins.
AB  - Carry-over effects take place when events occurring in one season influence
      individual performance in a subsequent season. Blood parasites (e.g. Plasmodium
      and Haemoproteus) have strong negative effects on the body condition of their
      hosts and could slow the rate of feather growth on the wintering grounds. In
      turn, these winter moult costs could reduce reproductive success in the following
      breeding season. In house martins Delichon urbica captured and studied at a
      breeding site in Europe, we used ptilochronology to measure growth rate of tail
      feathers moulted on the winter range in Africa, and assessed infection status of
      blood parasites transmitted on the wintering grounds. We found a negative
      association between haemosporidian parasite infection status and inferred growth
      rate of tail feathers. A low feather growth rate and blood parasite infections
      were related to a delay in laying date in their European breeding quarters. In
      addition, clutch size and the number of fledglings were negatively related to a
      delayed laying date and blood parasite infection. These results stress the
      importance of blood parasites and feather growth rate as potentially mechanisms
      driving carry-over effects to explain fitness differences in wild populations of
      migratory birds.

PMID- 22961371
TI  - Coupling in goshawk and grouse population dynamics in Finland.
AB  - Different prey species can vary in their significance to a particular predator.
      In the simplest case, the total available density or biomass of a guild of
      several prey species might be most relevant to the predator, but behavioural and
      ecological traits of different prey species can alter the picture. We studied the
      population dynamics of a predator-prey setting in Finland by fitting first-order
      log-linear vector autoregressive models to long-term count data from active
      breeding sites of the northern goshawk (Accipiter gentilis; 1986-2009), and to
      three of its main prey species (1983-2010): hazel grouse (Bonasa bonasia), black
      grouse (Tetrao tetrix) and capercaillie (T. urogallus), which belong to the same
      forest grouse guild and show synchronous fluctuations. Our focus was on modelling
      the relative significance of prey species and estimating the tightness of
      predator-prey coupling in order to explain the observed population dynamics,
      simultaneously accounting for effects of density dependence, winter severity and
      spatial correlation. We established nine competing candidate models, where
      different combinations of grouse species affect goshawk dynamics with lags of 1-3
      years. Effects of goshawk on grouse were investigated using one model for each
      grouse species. The most parsimonious model for goshawk indicated separate
      density effects of hazel grouse and black grouse, and different effects with lags
      of 1 and 3 years. Capercaillie showed no effects on goshawk populations, while
      the effect of goshawk on grouse was clearly negative only in capercaillie. Winter
      severity had significant adverse effects on goshawk and hazel grouse populations.
      In combination, large-scale goshawk-grouse population dynamics are coupled, but
      there are no clear mutual effects for any of the individual guild members. In a
      broader context, our study suggests that pooling data on closely related,
      synchronously fluctuating prey species can result in the loss of relevant
      information, rather than increased model parsimony.

PMID- 22961370
TI  - Contributions of detrital subsidies to aboveground spiders during secondary
      succession, revealed by radiocarbon and stable isotope signatures.
AB  - Prey subsidies originating from detritus add nutrients and energy to arboreal
      communities. Measurement of this subsidy is required in the understanding of how
      food web dynamics respond to changes in surrounding environments. Shrub spiders
      are one of the key predators involved in food web coupling. We evaluate the
      effects of potential changes in prey availabilities during secondary succession
      on the contribution of subsidy from detrital food webs to shrub spiders and how
      different spider feeding guilds used the subsidy of prey from detrital food webs.
      We measured the relative importance of the subsidy for the spider feeding guilds,
      using the ratios of stable isotopes of C (delta(13)C), and N (delta(15)N) and C
      isotope discrimination (Delta(14)C). Diet age was calculated from Delta(14)C
      values, because old diet ages of spiders indicate that the spiders consume prey
      from detrital food sources. Dominant aerial prey (Diptera) had a distinctively
      old diet age compared with arboreal prey, which indicates that aerial prey were
      subsidized from detrital food webs. Sit-and-wait spiders tended to have an older
      diet age than active hunting spiders, which indicates that sit-and-wait spiders
      depended more on subsidies. Diet age varied only slightly for spiders in stands
      of different ages, indicating that rates at which spiders use grazing and
      detrital prey are probably determined more by foraging strategies and not by
      stand age. A dominance of sit-and-wait predators will lead to higher detrital
      subsidy inputs in shrub habitats. This study highlights the effect of shrub
      spider community structure (feeding guild composition) on the volume of the
      subsidy received from the detrital food web.

PMID- 22961372
TI  - Inactivation or clearance of Coxiella burnetii in rat serum samples to enable
      safe serological testing.
AB  - To allow processing of serum samples from animals experimentally infected with
      Coxiella burnetii outside the BSL-3 facility, an inactivation or clearance
      protocol that does not hamper serological testing may be required. The effects of
      filtration (0.1 um pore size), heating at 56  degrees C for 30 min, addition of
      NaN3 (0.09% w/v), and combinations thereof on the presence of viable C. burnetii
      as well as OD-values in ELISA were tested. Only filtration was shown to
      effectively clear all culturable C. burnetii. 

PMID- 22961373
TI  - [Cardiac surgery in severe haemorrhagical diseases].
AB  - Cardiovascular diseases are the most common disorder in the developed countries.
      Invasive cardiological and cardiosurgical techniques are known therapies. Yet,
      patients with severe hereditary haemorrhagical diseases (haemophilia, rare
      deficiencies of coagulation factors) have an increased bleeding risk by the use
      of anticoagulants. Therefore, the treatment of these patients requires a
      concomitant therapy.  This article shows eight patients with a severe bleeding
      diathesis and cardiosurgical interventions in the years 2006 to 2011. This case
      report shall demonstrate that an adequate therapy can be accomplished with the
      help of a good cooperation between haemostaseologists and colleagues of the
      cardioinvasive/cardiosurgical disciplines.

PMID- 22961374
TI  - Ecosystem approaches to health for a global sustainability agenda.
AB  - International research agendas are placing greater emphasis on the need for more
      sustainable development to achieve gains in global health. Research using
      ecosystem approaches to health, and the wider field of ecohealth, contribute to
      this goal, by addressing health in the context of inter-linked social and
      ecological systems. We review recent contributions to conceptual development of
      ecosystem approaches to health, with insights from their application in
      international development research. Various similar frameworks have emerged to
      apply the approach. Most predicate integration across disciplines and sectors,
      stakeholder participation, and an articulation of sustainability and equity to
      achieve relevant actions for change. Drawing on several frameworks and on case
      studies, a model process for application of ecosystem approaches is proposed,
      consisting of an iterative cycles of participatory study design, knowledge
      generation, intervention, and systematization of knowledge. The benefits of the
      research approach include innovations that improve health, evidence-based
      policies that reduce health risks; empowerment of marginalized groups through
      knowledge gained, and more effective engagement of decision makers. With improved
      tools to describe environmental and economic dimensions, and explicit strategies
      for scaling-up the use and application of research results, the field of
      ecohealth will help integrate both improved health and sustainability into the
      development agenda.

PMID- 22961375
TI  - Renal amyloidosis in Behcet's disease: clinicopathologic features of 8 cases.
AB  - PURPOSE: Behcet's disease (BD) is a rare inflammatory disorder with variable
      articular and systemic manifestations. Amyloidosis is an uncommon complication of
      BD. The aim of this study is to present clinicopathological characteristics and
      outcome of 8 patients with renal amyloidosis secondary to BD. METHODS: A total of
      220 cases of secondary-type renal amyloidosis diagnosed over 26-year period (1981
      2007) in a single institution via needle biopsy were reviewed retrospectively,
      and accompanying BD was found in ten of them. Clinical and follow-up information
      of the patients was gathered from hospital records and computer-based data
      system. Two cases were excluded from the study due to another concomitant
      preamyloidotic condition. Biopsy slides of remaining 8 cases were culled from the
      archives and re-examined. Extent and pattern of renal amyloid deposition were
      explored. Amyloid typing was accomplished via immunohistochemistry. Factors
      acting on outcome and renal survival were explored. RESULTS: Patients were all
      male (age range 27-56). Duration of BD before diagnosis of amyloidosis varied
      from 24 to 192 months, and mean follow-up period was 89 months. Nephrotic
      syndrome was the most common presentation. Immunohistochemical typing revealed AA
      amyloid in all cases. Two cases showed glomerular-dominant, one case vascular
      dominant amyloid deposition, and rest were codominant glomerular and vascular,
      except one that was indeterminate. Patients were treated with steroids and/or
      different immunosuppressives, three progressed to end-stage kidney failure.
      CONCLUSION: Behcet's disease is one of the rare diseases that lead to AA
      amyloidosis. Morphology of renal amyloidosis due to BD has diversities in terms
      of differential amyloid deposition in renal compartments. Patients follow
      variable clinical courses accordingly.

PMID- 22961376
TI  - Bioaccumulation in freshwater crabs. Endosulfan accumulation in different tissues
      of Zilchiopsis collastinensis P. (Decapoda: Trichodactylidae).
AB  - We examined the bioaccumulation of alpha- and beta-endosulfan and endosulfan
      sulfate in tissues from the crab Zilchiopsis collastinensis. There was more
      endosulfan accumulated in the hepatopancreas (from <2 to 467.8 ng g(-1)) than in
      the gonads (from <2 to 52.1 ng g(-1)) or muscles (<2 ng g(-1)). The endosulfan
      concentrations in the hepatopancreas decreased over time and with the endosulfan
      dilution (p < 0.05). In the gonads there was little bioaccumulation, which did
      not vary over time (p > 0.05). The hepatopancreas is a dynamic organ that is able
      to depurate itself, whereas the gonads act as a sink for pesticides.

PMID- 22961377
TI  - Enantioselective inhibition of dichlorprop on catalase.
AB  - The enantioselectivity interaction of 2,4-dichlorprop (DCPP) and catalase were
      studied, and it was further evaluated with the presence of humus. Both of rac
      DCPP and R-DCPP can inhibit the activity of catalase with the concentrations of
      0.05-80 mg L(-1), the inhibitory type of rac-DCPP was uncompetitive, and of R
      DCPP was complex. The presence of humic acid has changed the inhibitory ability
      of DCPP on catalase, the inhibition of rac-DCPP disappeared and the inhibition
      type of R-DCPP mainly became uncompetitive. These results suggest that inhibition
      of chiral DCPP on catalase is enantioselective.

PMID- 22961378
TI  - Asymmetric synthesis of a highly functionalized enantioenriched system close to
      thapsigargin framework.
AB  - A straightforward approach to a highly functionalized enantioenriched
      bicyclo[5.3.0]decadienone system close to the thapsigargin framework has been
      achieved. The developed synthetic route involves two main stages: installation of
      the chains on either side of the quaternary center at C7 starting from a central
      enantiopure epoxide and formation of the bicyclic octahydroazulene through
      subsequent Pauson-Khand annelation.

PMID- 22961379
TI  - Argonaute proteins couple chromatin silencing to alternative splicing.
AB  - Argonaute proteins play a major part in transcriptional gene silencing in many
      organisms, but their role in the nucleus of somatic mammalian cells remains
      elusive. Here, we have immunopurified human Argonaute-1 and Argonaute-2 (AGO1 and
      AGO2) chromatin-embedded proteins and found them associated with chromatin
      modifiers and, notably, with splicing factors. Using the CD44 gene as a model, we
      show that AGO1 and AGO2 facilitate spliceosome recruitment and modulate RNA
      polymerase II elongation rate, thereby affecting alternative splicing. Proper
      AGO1 and AGO2 recruitment to CD44 transcribed regions required the endonuclease
      Dicer and the chromobox protein HP1gamma, and resulted in increased histone H3
      lysine 9 methylation on variant exons. Our data thus uncover a new model for the
      regulation of alternative splicing, in which Argonaute proteins couple RNA
      polymerase II elongation to chromatin modification.

PMID- 22961380
TI  - Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon
      junction complex assembly.
AB  - The exon-junction complex (EJC) functionally links splicing to subsequent mRNA
      localization, translation and stability. Sequence-independent binding of the EJC
      core to RNA is ensured by the DEAD-box helicase eIF4AIII. Here, we identified the
      splicing factor CWC22 as a new eIF4AIII partner in flies and humans. CWC22
      coexists with eIF4AIII in large protein complexes distinct from EJCs. Recombinant
      CWC22 directly contacts eIF4AIII and prevents it from binding RNA. In vitro
      splicing assays revealed that CWC22 introduces eIF4AIII to spliceosomes before
      remodeling to facilitate eIF4AIII incorporation into the EJC. Finally, using
      knockdowns in vivo, we showed that CWC22 is essential for EJC assembly. We
      elucidated the initial step of EJC assembly and the duality of CWC22 function
      that hinders eIF4AIII from nonspecifically binding RNA and escorts it to the
      splicing machinery to promote EJC assembly on mature mRNAs.

PMID- 22961381
TI  - Dxo1 is a new type of eukaryotic enzyme with both decapping and 5'-3'
      exoribonuclease activity.
AB  - Recent studies showed that Rai1 is a crucial component of the mRNA 5'-end-capping
      quality-control mechanism in yeast. The yeast genome encodes a weak homolog of
      Rai1, Ydr370C, but little is known about this protein. Here we report the crystal
      structures of Ydr370C from Kluyveromyces lactis and the first biochemical and
      functional studies on this protein. The overall structure of Ydr370C is similar
      to Rai1. Ydr370C has robust decapping activity on RNAs with unmethylated caps,
      but it has no detectable pyrophosphohydrolase activity. Unexpectedly, Ydr370C
      also possesses distributive, 5'-3' exoRNase activity, and we propose the name
      Dxo1 for this new eukaryotic enzyme with both decapping and exonuclease
      activities. Studies of yeast in which both Dxo1 and Rai1 are disrupted reveal
      that mRNAs with incomplete caps are produced even under normal growth conditions,
      in sharp contrast to current understanding of the capping process.

PMID- 22961383
TI  - Admission and capacity planning for the implementation of one-stop-shop in skin
      cancer treatment using simulation-based optimization.
AB  - Hospitals and health care institutions are facing the challenge of improving the
      quality of their services while reducing their costs. The current study presents
      the application of operations management practices in a dermatology oncology
      outpatient clinic specialized in skin cancer treatment. An interesting
      alternative considered by the clinic is the implementation of a one-stop-shop
      concept for the treatment of new patients diagnosed with basal cell carcinoma.
      This alternative proposes a significant improvement in the average waiting time
      that a patient spends between the diagnosis and treatment. This study is focused
      on the identification of factors that influence the average throughput time of
      patients treated in the clinic from the logistic perspective. A two-phase
      approach was followed to achieve the goals stated in this study. The first phase
      included an integrated approach for the deterministic analysis of the capacity
      using a demand-supply model for the hospital processes, while the second phase
      involved the development of a simulation model to include variability to the
      activities involved in the process and to evaluate different scenarios. Results
      showed that by managing three factors: the admission rule, resources allocation
      and capacity planning in the dermato-oncology unit throughput times for
      treatments of new patients can be decreased with more than 90 %, even with the
      same resource level. Finally, a pilot study with 16 patients was also conducted
      to evaluate the impact of implementing the one stop shop concept from a clinical
      perspective. Patients turned out to be satisfied with the fast diagnosis and
      treatment.

PMID- 22961382
TI  - 5-hmC in the brain is abundant in synaptic genes and shows differences at the
      exon-intron boundary.
AB  - The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is
      abundant in the brain for unknown reasons. Here we characterize the genomic
      distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by
      using glucosylation coupled with restriction-enzyme digestion and microarray
      analysis. We detected 5-hmC enrichment in genes with synapse-related functions in
      both human and mouse brain. We also identified substantial tissue-specific
      differential distributions of these DNA modifications at the exon-intron boundary
      in human and mouse. This boundary change was mainly due to 5-hmC in the brain but
      due to 5-mC in non-neural contexts. This pattern was replicated in multiple
      independent data sets and with single-molecule sequencing. Moreover, in human
      frontal cortex, constitutive exons contained higher levels of 5-hmC relative to
      alternatively spliced exons. Our study suggests a new role for 5-hmC in RNA
      splicing and synaptic function in the brain.

PMID- 22961384
TI  - Beneficial effects of taurine and carnosine in experimental ischemia/reperfusion
      injury in testis.
AB  - PURPOSE: Testicular torsion can be thought of as an ischemia/reperfusion (I/R)
      injury to the testis. This study aimed to investigate the effects of taurine
      (TAU) and carnosine (CAR), which are strong antioxidants, on experimental
      testicular I/R injury model. METHODS: Male Wistar albino rats were divided into
      four groups with eight animals in each. A sham operation was performed in group
      1. To create testicular I/R, the left testis was torsioned 720 degrees  for 2 h
      followed by 2 h of detorsion. Groups 2 (I/R), 3 (I/R + TAU) and 4 (I/R + CAR)
      received intraperitoneal saline, TAU (250 mg/kg) and CAR (250 mg/kg),
      respectively, 1 h before detorsion. Thiobarbituric acid reactive substances
      (TBARS), diene conjugate (DC), protein carbonyls (PC), nonprotein sulfhydryl
      (NPSH), and vitamin C levels were measured in testis tissues as well as
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities.
      Histopathological evaluation was also performed. RESULTS: TBARS, DC, and PC
      levels were significantly increased in I/R group. TAU and CAR did not alter TBARS
      levels, but decreased the elevated DC and PC levels. There were no changes in
      testicular NPSH levels, SOD, and GPx activities in all groups; however, vitamin C
      significantly decreased in I/R group. CAR treatment was found to increase vitamin
      C levels as compared to I/R group. Histopathologically, both I/R + TAU and I/R +
      CAR groups showed significant increase in testicular spermatogenesis in
      comparison to I/R group. CONCLUSION: Our results indicate that TAU and CAR
      reduces oxidative stress and may have a protective role in testicular I/R injury.

PMID- 22961385
TI  - Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord
      grape juice.
AB  - After acute ingestion of 350 ml of Concord grape juice, containing 528 MUmol of
      (poly)phenolic compounds, by healthy volunteers, a wide array of phase I and II
      metabolites were detected in the circulation and excreted in urine. Ingestion of
      the juice by ileostomists resulted in 40% of compounds being recovered intact in
      ileal effluent. The current study investigated the fate of these undigested
      (poly)phenolic compounds on reaching the colon. This was achieved through
      incubation of the juice using an in vitro model of colonic fermentation and
      through quantification of catabolites produced after colonic degradation and
      their subsequent absorption prior to urinary excretion by healthy subjects and
      ileostomy volunteers. A total of 16 aromatic and phenolic compounds derived from
      colonic metabolism of Concord grape juice (poly)phenolic compounds were
      identified by GC-MS in the faecal incubation samples. Thirteen urinary phenolic
      acids and aromatic compounds were excreted in significantly increased amounts
      after intake of the juice by healthy volunteers, whereas only two of these
      compounds were excreted in elevated amounts by ileostomists. The production of
      phenolic acids and aromatic compounds by colonic catabolism contributed to the
      bioavailability of Concord grape (poly)phenolic compounds to a much greater
      extent than phase I and II metabolites originating from absorption in the upper
      gastrointestinal tract. Catabolic pathways are proposed, highlighting the impact
      of colonic microbiota and subsequent phase II metabolism prior to excretion of
      phenolic compounds derived from (poly)phenolic compounds in Concord grape juice,
      which pass from the small to the large intestine.

PMID- 22961386
TI  - Cancer incidence in South Asian migrants to England, 1986-2004: unraveling ethnic
      from socioeconomic differentials.
AB  - Studies on cancer in migrants are informative about the relative influence of
      environmental and genetic factors on cancer risk. This study investigates trends
      in incidence from colorectal, lung, breast and prostate cancer in England among
      South Asians and examines the influence of deprivation, a key environmental
      exposure. South Asian ethnicity was assigned to patients recorded in the
      population-based National Cancer Registry of England during 1986-2004, using the
      computerized algorithm SANGRA: South Asian Names and Groups Recognition
      Algorithm. Population denominators were derived from population censuses.
      Multivariable flexible (splines) Poisson models were used to estimate trends and
      socioeconomic differentials in incidence in South Asians compared to non-South
      Asians. Overall, age-adjusted cancer incidence in South Asians was half that in
      non-South Asians but rose over time. Cancer-specific incidence trends and
      patterns by age and deprivation differed widely between the two ethnic groups. In
      contrast to non-South Asians, lung cancer incidence in South Asians did not fall.
      Colorectal and breast cancer incidence rose in both groups, more steeply in South
      Asians though remaining less common than in non-South Asians. The deprivation
      gaps in cancer-specific incidence were much less marked among South Asians,
      explaining some of the ethnic differences in overall incidence. Although still
      lower than in non-South Asians, cancer incidence is rising in South Asians,
      supporting the concept of transition in cancer incidence among South Asians
      living in England. Although these trends vary by cancer, they have important
      implications for both prevention and anticipating health-care demand.

PMID- 22961388
TI  - Investigating the effects of metals on phenol oxidase-producing nitrogen-fixing
      Azotobacter chroococcum.
AB  - Expression of phenol oxidases (PO) in bacteria is often observed during
      physiological and morphological changes; in the nitrogen-fixing strain
      Azotobacter chroococcum SBUG 1484, it is accompanied by the formation of encysted
      cells and melanin. Herein, we studied the effects of copper and the depletion of
      the nitrogenase-relevant metals molybdenum and iron on physiological
      characteristics such as culture pigmentation, release of ortho-dihydroxylated
      melanin precursors, and expression of PO activity in A. chroococcum. Biomass
      production and melanogenic appearance were directly affected by the depletion of
      either iron or molybdenum, or in the absence of both metals. Only nitrogen-fixing
      cells growing in the presence of both metals and cultures supplemented with iron
      (molybdenum starved) showed the ability to produce an intensively brown-black
      melanin pigment typically associated with A. chroococcum. Accordingly, PO
      production was only detected in the presence of both metals and in iron
      supplemented cultures starved of molybdenum. The total amount of catecholate
      siderophores produced by nitrogen-fixing melanogenic cells was considerably
      higher than in cultures starved of metal ions. Induction of enhanced PO activity
      was stimulated by additional copper sulfate, possibly related to cellular
      processes involved in the detoxification of this particular metal, and revealed
      distinct release of the ortho-dihydroxylated melanin precursors catechol and 3,4
      dihydroxybenzoic acid.

PMID- 22961387
TI  - Relationships of race and socioeconomic status to postpartum depressive symptoms
      in rural African American and non-Hispanic white women.
AB  - This study examines the potential racial disparity in postpartum depression (PPD)
      symptoms among a cohort of non-Hispanic white and African American women after
      taking into consideration the influence of socioeconomic status (SES).
      Participants (N = 299) were recruited from maternity clinics serving rural
      counties, with oversampling of low SES and African Americans. The Edinburgh
      Postnatal Depression Scale (EPDS) was administered 1 and 6 months postpartum, and
      subjective SES scale at 6 months postpartum. Demographic information was
      collected during enrollment and 1 month postpartum, with updates at 6 months
      postpartum. Separate logistic regressions were conducted for 1 and 6 month time
      points for minor-major PPD (EPDS >= 10) and major PPD (EPDS > 12); with marital
      status, poverty, education, subjective SES, and race predictors entered in block
      sequence. After including all other predictors, race was not a significant
      predictor of minor-major or major PPD at 1 or 6 months postpartum. Subjective SES
      was the most consistent predictor of PPD, being significantly associated with
      minor-major PPD and major PPD at 6 months postpartum, with higher subjective SES
      indicating lower odds of PPD, even after accounting for all other predictors.
      This study shows that significant racial disparities were not observed for minor
      major or major PPD criteria at 1 or 6 months postpartum. The most consistent and
      significant predictor of PPD was subjective SES. Implications of these findings
      for future research, as well as PPD screening and intervention are discussed. 

PMID- 22961389
TI  - [Melanoma in children: diagnosis and treatment specificities].
AB  - Skin melanoma is an extremely rare disease at pediatric age and its incidence
      increases with age. Links with predisposition syndrome exists (giant congenital
      naevus, xeroderma pigmentosum). Diagnosis is often difficult and distinction
      between benign or malignant lesion is sometime impossible (Spitzoid naevus,
      melanocytic neoplasms) leading to the diagnosis of "melanocytic tumor of
      uncertain malignant potential" (MELTUMP). Atypical features (amelanotic or raised
      lesions, atypical histotype) are frequent leading to delay in treatment.
      Diagnosis and treatment require expertise for pathologists and dermatologists
      pediatricians. Invasive melanomas are of poor prognosis despite recent progress
      in adult treatment. Early and rigorous treatment of suspect skin lesions is
      necessary.

PMID- 22961391
TI  - Growth characteristics of three Fusarium species evaluated by near-infrared
      hyperspectral imaging and multivariate image analysis.
AB  - Colony growth of three Fusarium spp. on potato dextrose agar was followed by
      collecting near-infrared (NIR) hyperspectral images of the colonies at regular
      intervals after inoculation up to 55 h. After principal component analysis (PCA),
      two clusters were apparent in the score plot along principal component 1. Using
      the brushing technique, these clusters were divided into four groups of pixels
      with similar score values. These could be visualised as growth zones within the
      colonies in the corresponding score image. Three spectral bands, i.e. 1,166,
      1,380 and 1,918 nm, were prominent in the multiplicative scatter corrected and
      Savitzky-Golay second derivative spectra. These indicated chemical changes,
      associated with carbohydrates (1,166 and 1,380 nm) and protein (1,918 nm), that
      occurred as the mycelium grew and matured. The protein band was more prominent in
      the mature fungal material while the carbohydrate band was less pronounced. The
      younger material and the agar were characterised by the carbohydrate spectral
      band. Integrating whole mycelium colonies as the sum of pixels over time made it
      possible to construct curves that resembled growth curves; this included the lag
      phase, active growth phase, deceleration phase and phase of constant growth.
      Growth profiles constructed from individual growth zones indicated more detailed
      growth characteristics. The use of NIR hyperspectral imaging and multivariate
      image analysis (MIA) allowed one to visualise radial growth rings in the PCA
      score images. This would not have been possible with bulk spectroscopy.
      Interpreting spectral data enabled better understanding of microbial growth
      characteristics on agar medium. NIR hyperspectral imaging combined with MIA is a
      powerful tool for the evaluation of growth characteristics of fungi.

PMID- 22961390
TI  - Regulatory pathways for ATP-binding cassette transport proteins in kidney
      proximal tubules.
AB  - The ATP-binding cassette transport proteins (ABC transporters) represent
      important determinants of drug excretion. Protective or excretory tissues where
      these transporters mediate substrate efflux include the kidney proximal tubule.
      Regulation of the transport proteins in this tissue requires elaborate signaling
      pathways, including genetic, epigenetic, nuclear receptor mediated,
      posttranscriptional gene regulation involving microRNAs, and non-genomic
      (kinases) pathways triggered by hormones and/or growth factors. This review
      discusses current knowledge on regulatory pathways for ABC transporters in kidney
      proximal tubules, with a main focus on P-glycoprotein, multidrug resistance
      proteins 2 and 4, and breast cancer resistance protein. Insight in these
      processes is of importance because variations in transporter activity due to
      certain (disease) conditions could lead to significant changes in drug efficacy
      or toxicity.

PMID- 22961393
TI  - Subglottic injury: a clinically relevant animal model.
AB  - OBJECTIVES/HYPOTHESIS: To develop a clinically aligned, reproducible model for
      subglottic injury. STUDY DESIGN: Prospective randomized control pilot study.
      METHODS: Juvenile (3-month-old) New Zealand White rabbits underwent intubation
      with a 3-cm length of an endotracheal tube that was chosen so that there would be
      no air leak below 20 cm of water. This tube was one or two sizes above the
      appropriate tube for the animal. It was held in situ with a suture placed at the
      trachea and secured over a button in the neck for a period of 1 week. Animals
      were sacrificed 1 week postextubation, and larynges were harvested. A range of
      histological techniques and gross morphology were utilized to examine the injury
      caused at the level of the subglottis. Unintubated animals constituted controlled
      specimens. RESULTS: Intubated animals demonstrated considerable histopathology
      including evidence of ulceration, inflammation, granulation tissue,
      perichondritis, and chondritis when compared with control animals. Morphometric
      analysis demonstrated a significant increase in lamina propria thickness (P =
      .0013), mucosal thickness (P <= .0001), and in goblet cell areal density (P =
      .014). Analysis of mucin types found a significant decrease in acidic (P = .0001)
      mucin coinciding with a significant increase in mixed mucin types (P = .0013).
      CONCLUSIONS: Our model provides a reliable and reproducible technique for
      acute/subacute injury to the subglottis secondary to intubation, which is
      consistent with previous histological findings of early changes associated with
      acquired subglottic stenosis (SGS). Future uses of this model could include the
      examination of current adjunctive therapies and their effects on limiting
      progression to SGS.

PMID- 22961394
TI  - A novel dextran dextrinase from Gluconobacter oxydans DSM-2003: purification and
      properties.
AB  - Dextran has already been widely applied in food, pharmaceutical, and chemical
      industries. In this study, a novel intracellular dextran dextrinase (DDase, EC
      2.4.1.2) from Gluconobacter oxydans DSM-2003 exhibiting catalytic activity to
      synthesize dextran from maltodextrin was purified to homogeneity by ultrasonic
      cell disruption, ion exchange chromatography, and gel filtration. This procedure
      showed 187.5-fold purification from the cell-free extract with 41.9 % yield. And
      the apparent molecular weight was estimated to be 62 kDa by SDS-PAGE. It was
      different from the reported literatures, which found that the molecular weight of
      intracellular and extracellular DDase of G. oxydans ATCC-11894 was 300 and 152
      kDa, respectively. Otherwise, it showed different physicochemical characteristics
      (optimal temperature and pH, thermal, pH stability, effect of metal ions) from
      the DDase of G. oxydans ATCC-11894. This indicated that DDase of G. oxydans DSM
      2003 was a novel one compared to the reported literatures.

PMID- 22961395
TI  - Use of styrene as sole carbon source by the fungus Exophiala oligosperma:
      optimization and modeling of biodegradation, pathway elucidation, and cell
      membrane composition.
AB  - Biodegradation of styrene by Exophiala sp. was tested at different initial
      concentrations (19.3-170.6 mgl(-1)), pH (2.8-8.7), and temperatures (19.8-45.1 
      degrees C), for 120 h according to a 2(3) full-factorial central composite
      design. The specific growth rate (SGR, per hour) and specific styrene utilization
      rate (SUR, milligrams of styrene per milligram of biomass per hour) values were
      used as the response variables for optimization purposes. The interactions
      between concentration and temperature (P=0.022), and pH and temperature (P=0.010)
      for SGR, and interactions between concentration and temperature (P=0.012) for SUR
      were found to be statistically significant. The optimal values for achieving high
      SGR (0.15 h(-1)) and SUR (0.3622 mg styrene mg(-1) biomass h(-1)) were calculated
      from the regression model equation. Those values are C(o)=89.1 mgl(-1), pH=5.4,
      and T=31.5  degrees C for SGR and C(o)=69.2 mgl(-1), pH=5.5, and T=32.4  degrees
      C for SUR. It was also observed that the Exophiala strain degrades styrene via
      phenylacetic acid, involving initial oxidation of the vinyl side chain. Besides,
      in the presence of styrene, changes in the fatty acids profile were also
      observed. It is hypothesized that an increasing amount of linoleic acid (18:2)
      may be involved in the protection of the fungus against toxic substrate.

PMID- 22961396
TI  - Suppression subtractive hybridization and comparative expression analysis to
      identify developmentally regulated genes in filamentous fungi.
AB  - Ascomycetes differentiate four major morphological types of fruiting bodies
      (apothecia, perithecia, pseudothecia and cleistothecia) that are derived from an
      ancestral fruiting body. Thus, fruiting body differentiation is most likely
      controlled by a set of common core genes. One way to identify such genes is to
      search for genes with evolutionary conserved expression patterns. Using
      suppression subtractive hybridization (SSH), we selected differentially expressed
      transcripts in Pyronema confluens (Pezizales) by comparing two cDNA libraries
      specific for sexual and for vegetative development, respectively. The expression
      patterns of selected genes from both libraries were verified by quantitative real
      time PCR. Expression of several corresponding homologous genes was found to be
      conserved in two members of the Sordariales (Sordaria macrospora and Neurospora
      crassa), a derived group of ascomycetes that is only distantly related to the
      Pezizales. Knockout studies with N. crassa orthologues of differentially
      regulated genes revealed a functional role during fruiting body development for
      the gene NCU05079, encoding a putative MFS peptide transporter. These data
      indicate conserved gene expression patterns and a functional role of the
      corresponding genes during fruiting body development; such genes are candidates
      of choice for further functional analysis. 

PMID- 22961397
TI  - Functional role of the putative iron ligands in the ferroxidase activity of
      recombinant human hephaestin.
AB  - Hephaestin is a multicopper ferroxidase expressed mainly in the mammalian small
      intestine. The ferroxidase activity of hephaestin is thought to play an important
      role during iron export from intestinal enterocytes and the subsequent iron
      loading of the blood protein transferrin, which delivers iron to the tissues.
      Structurally, the ectodomain of hephaestin is predicted to resemble
      ceruloplasmin, the soluble ferroxidase of blood. In this study, the human
      hephaestin ectodomain was expressed in baby hamster kidney cells and purified to
      electrophoretic homogeneity. Ion exchange chromatography of purified recombinant
      human hephaestin (rhHp) resulted in the isolation of hephaestin fractions with
      distinct catalytic and spectroscopic properties. The fraction of rhHp with the
      highest enzymatic activity also showed an enhanced molar absorptivity at 600 nm,
      characteristic of type 1 copper sites. Kinetic analysis revealed that rhHp
      possesses both high-affinity and low-affinity binding sites for ferrous iron. To
      investigate the role of particular residues in iron specificity of hephaestin,
      mutations of putative iron ligands were introduced into rhHp using site-directed
      mutagenesis. Kinetic analysis of ferroxidation rates of wild-type rhHp and
      mutants demonstrated the important roles of hephaestin residues E960 and H965 in
      the observed ferroxidase activity.

PMID- 22961398
TI  - The DNA sequence specificity of bleomycin cleavage in telomeric sequences in
      human cells.
AB  - Bleomycin is an antibiotic drug that is widely used in cancer chemotherapy.
      Telomeres are located at the ends of chromosomes and comprise the tandemly
      repeated DNA sequence (GGGTTA)( n ) in humans. Since bleomycin cleaves DNA at 5'
      GT dinucleotide sequences, telomeres are expected to be a major target for
      bleomycin cleavage. In this work, we determined the DNA sequence specificity of
      bleomycin cleavage in telomeric sequences in human cells. This was accomplished
      using a linear amplification procedure, a fluorescently labelled oligonucleotide
      primer and capillary gel electrophoresis with laser-induced fluorescence
      detection. This represents the first occasion that the DNA sequence specificity
      of bleomycin cleavage in telomeric DNA sequences in human cells has been
      reported. The bleomycin DNA sequence selectivity was mainly at 5'-GT
      dinucleotides, with lesser amounts at 5'-GG dinucleotides. The cellular bleomycin
      telomeric DNA damage was also compared with bleomycin telomeric damage in
      purified human genomic DNA and was found to be very similar. The implications of
      these results for the understanding of bleomycin's mechanism of action in human
      cells are discussed.

PMID- 22961400
TI  - Does dispersal ability affect the relative importance of environmental control
      and spatial structuring of littoral macroinvertebrate communities?
AB  - Both spatial processes and environmental control may structure metacommunities,
      but their relative importance may be contingent on the dispersal ability of
      organisms. I examined the roles of spatial and environmental factors for the
      structuring of littoral macroinvertebrate communities across a set of lakes in a
      boreal drainage basin. I hypothesized that dispersal ability would affect the
      relative importance of spatial processes and environmental control, and thus the
      biological data were divided into four groups of species differing in dispersal
      ability. In general, the group of the strongest aerial dispersers showed greatest
      relative pure environmental control and least pure spatial structuring of
      community structure and species richness, while spatial processes seemed to be
      more important for the other three dispersal ability groups. However, these
      results were contingent on the indirect measure of spatial processes, with the
      spatial variables and connectivity variables providing slightly different
      insights into the spatial processes and environmental control of metacommunity
      structuring. It appears, however, that dispersal ability has effects on the
      spatial processes and environmental control important in metacommunity
      organization, with strong dispersers being more under environmental control and
      less affected by spatial processes compared to weak dispersers.

PMID- 22961401
TI  - Antiinflammatory and chondroprotective effects of intraarticular injection of
      adipose-derived stem cells in experimental osteoarthritis.
AB  - OBJECTIVE: In experimental collagenase-induced osteoarthritis (OA) in the mouse,
      synovial lining macrophages are crucial in mediating joint destruction. It was
      recently shown that adipose-derived stem cells (ASCs) express immunosuppressive
      characteristics. This study was undertaken to explore the effect of
      intraarticular injection of ASCs on synovial lining thickness and its relation to
      joint pathology in experimental mouse OA. METHODS: ASCs were isolated from fat
      surrounding the inguinal lymph nodes and cultured for 2 weeks. Experimental OA
      was induced by injection of collagenase into the knee joints of C57BL/6 mice. OA
      phenotypes were measured within 8 weeks after induction. Histologic analysis was
      performed, and synovial thickening, enthesophyte formation, and cartilage
      destruction were measured in the knee joint. RESULTS: ASCs were injected into the
      knee joints of mice 7 days after the induction of collagenase-induced OA. On day
      1, green fluorescent protein-labeled ASCs were attached to the lining layer in
      close contact with macrophages. Thickening of the synovial lining, formation of
      enthesophytes associated with medial collateral ligaments, and formation of
      enthesophytes associated with cruciate ligaments were significantly inhibited on
      day 42 after ASC treatment, by 31%, 89%, and 44%, respectively. Destruction of
      cartilage was inhibited on day 14 (65%) and day 42 (35%). In contrast to early
      treatment, injection of ASCs on day 14 after OA induction showed no significant
      effect on synovial activation or joint pathology on day 42. CONCLUSION: These
      findings indicate that a single injection of ASCs into the knee joints of mice
      with early-stage collagenase-induced OA inhibits synovial thickening, formation
      of enthesophytes associated with ligaments, and cartilage destruction.

PMID- 22961402
TI  - CD55 polymorphisms and risk of aspirin-exacerbated respiratory disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is a respiratory disease
      characterized by acute bronchial responses upon the administration of non
      steroidal anti-inflammatory drugs (NSAIDs) and the immune response by mast cells
      is regarded as one of the noteworthy causes of AERD pathogenesis. The complement
      cascade is regarded as a key mechanism for clearing pathogens from the host. CD55
      is one of the proteins involved in self-recognition, a central component of the
      complement system and autoimmunity. To investigate the associations between CD55
      single nucleotide polymorphisms (SNPs) and the risk of AERD, we carried out
      logistic analyses with three genetic models and further regression analysis was
      performed with the fall rate of forced expiratory volume in 1 sec (FEV1) by
      aspirin provocation. However, our results demonstrate that no CD55 polymorphisms
      are associated with the risk of AERD and the fall rate of FEV1 (P>0.05).
      Therefore, our results suggest that CD55 polymorphisms are not genetic markers of
      aspirin-induced bronchospasm, including FEV1, in the population studied. Although
      the genetic role of CD55 has been found to be integral to human immunity, our
      results indicate that genetic variations of CD55 do not influence the risk of
      AERD and the fall rate of FEV1 in the population studied.

PMID- 22961403
TI  - [Severe and moderate haemophilia under prophylactic replacement treatment-
      maximal knee extensor and flexor torque of children and adolescents].
AB  - Due to its influence on haemophilic arthropathy, the evaluation of knee extensor
      (K(Ext)) and flexor (K(Flex)) torques plays an important role in the preventive
      and rehabilitative context of haemophilia. Thus, the present study aimed at
      investigating maximal static torque (M(Max)) of K(Ext) and K(Flex). 14 boys with
      haemophilia (8 severe, 6 moderate; age: 11.7 +/- 2.8 years; prophylactic
      treatment > 5 years) and 14 healthy carefully pair-matched controls (age: 11.5 +/
      2.7 years) were separately measured for the left and right leg for M(Max).
      Furthermore, the ratio K(Flex)/K(Ext )was calculated and the joint situation
      assessed using the Haemophilia Joint Health Score. RESULTS: No significant group
      effect was observed for M(Max) of the K(Ext) and K(Flex) as well as for the ratio
      K(Flex)/K(Ext) (p>0.05). Despite significant higher joint scores in haemophilic
      children compared to their healthy controls (p<0.01), patients merely showed
      minor joint impairments. CONCLUSION: Children and adolescents with severe and
      moderate haemophilia under prophylactic replacement treatment with a good joint
      status showed comparable maximal strength performance of relevant knee muscles
      compared to their healthy peers.

PMID- 22961404
TI  - Sequence comparisons of global chrysanthemum stunt viroid variants: multiple
      polymorphic positions scattered through the viroid genome.
AB  - The nucleotide sequences of cDNA clones of three chrysanthemum stunt viroid
      (CSVd) isolates (one each from the USA, China, and Australia) were determined and
      analyzed. The sequences of CSVd cDNA clones of the US and Australian isolates
      were both quasi-species, while the cDNA clones of the Chinese isolate contained
      only a single variant. A comparison of the nucleotide sequences of 117 isolates
      and cDNA clones obtained from 16 countries showed that in some cases identical
      CSVd isolates were found in several countries and from multiple locations within
      the same country. CSVd isolates differed as much in sequence between countries as
      within countries. Sequence variation was observed at 103 sites scattered through
      the CSVd genome, and was not associated predominantly with a single variable
      region, as was the case with several other viroids. While some sequence changes
      were associated with CSVd found in other host species, it is unknown if these
      changes are required for infection of those species.

PMID- 22961405
TI  - Optimal approach to sporadic desmoid tumors: from radical surgery to observation.
      Time for a consensus?

PMID- 22961406
TI  - New method for effectively and quantitatively labeling cysteine residues on
      chicken eggshell membrane.
AB  - Using maleimidoethylmonoamide cysteine (Fmoc)(StBu) (1) as a medium, cysteine
      residues on proteins of chicken eggshell membrane (ESM) were successfully
      converted into N-terminal cysteines. After a biocompatible condensation reaction
      between the N-terminal cysteine and fluorescent probe 2-cyanobenzothiazole-Gly
      Gly-Gly-fluorescein isothiocyanate (2), a new fluorogenic structure luciferin-Gly
      Gly-Gly-FITC (3) was obtained, which exhibits a 2-fold fluorescence emission
      increase compared to that of 2. Thus, a new method for effectively labeling
      cysteine residues on ESMs was developed. Enhanced fluorescence images of ESMs
      were directly observed under a microscope and a small animal imaging machine.

PMID- 22961407
TI  - DNA and protein adducts in human tissues resulting from exposure to tobacco
      smoke.
AB  - Tobacco smoke contains a variety of genotoxic carcinogens that form adducts with
      DNA and protein in the tissues of smokers. Not only are these biochemical events
      relevant to the carcinogenic process, but the detection of adducts provides a
      means of monitoring exposure to tobacco smoke. Characterization of smoking
      related adducts has shed light on the mechanisms of smoking-related diseases and
      many different types of smoking-derived DNA and protein adducts have been
      identified. Such approaches also reveal the potential harm of environmental
      tobacco smoke (ETS) to nonsmokers, infants and children. Because the majority of
      tobacco-smoke carcinogens are not exclusive to this source of exposure, studies
      comparing smokers and nonsmokers may be confounded by other environmental
      sources. Nevertheless, certain DNA and protein adducts have been validated as
      biomarkers of exposure to tobacco smoke, with continuing applications in the
      study of ETS exposures, cancer prevention and tobacco product legislation. Our
      article is a review of the literature on smoking-related adducts in human tissues
      published since 2002.

PMID- 22961408
TI  - Occurrence of arbuscular mycorrhizas and dark septate endophytes in pteridophytes
      from a Patagonian rainforest, Argentina.
AB  - Arbuscular mycorrhizas (AM) are one of the most widespread types of symbiotic
      associations. Pteridophytes occupy an important position in the evolution of
      vascular plants. However, their mycorrhizal state remains poorly understood. The
      aim of this work was to describe the general mycorrhizal status and the
      occurrence of dark septate endophytes (DSE) in the pteridophytic flora of a
      Valdivian temperate forest in Patagonia, Argentina. First, the roots of nine
      terrestrial species representing six families were examined, and this information
      was then compared with other surveys concerning the occurrence of AM in other
      pteridophytic species within the same Valdivian temperate forest. AM were
      recorded in 98.6% of the samples analyzed in this work and all of them
      corresponded to the Paris-type morphology. DSEs were also present within the
      roots of all terrestrial species. A comparison to published results in other
      ferns and lycophytes that have been studied in this Valdivian temperate forest
      (161 sporophytes, 21 species and 10 families) was made. Clear differences in
      colonization patterns between eusporangiate/leptosporangiate and
      epiphytic/terrestrial species became evident and are discussed.

PMID- 22961409
TI  - Force-induced fibronectin assembly and matrix remodeling in a 3D microtissue
      model of tissue morphogenesis.
AB  - Encapsulations of cells in type-I collagen matrices are widely used three
      dimensional (3D) in vitro models of wound healing and tissue morphogenesis and
      are common constructs for drug delivery and for in vivo implantation. As cells
      remodel the exogenous collagen scaffold, they also assemble a dense fibronectin
      (Fn) matrix that aids in tissue compaction; however, the spatio-temporal
      (re)organization of Fn and collagen in this setting has yet to be quantitatively
      investigated. Here, we utilized microfabricated tissue gauges (MUTUGs) to guide
      the contraction of microscale encapsulations of fibroblasts within collagen gels.
      We combined this system with a Foerster Radius Energy Transfer (FRET) labeled
      biosensor of Fn conformation to probe the organization, conformation and
      remodeling of both the exogenous collagen and the cell-assembled Fn matrices. We
      show that within hours, compact Fn from culture media adsorbed to the collagen
      scaffold. Over the course of tissue remodeling, this Fn-coated collagen scaffold
      was compacted into a thin, sparsely populated core around which cells assembled a
      dense fibrillar Fn shell that was rich in both cell and plasma derived Fn. This
      resulted in two separate Fn populations with different conformations
      (compact/adsorbed and extended/fibrillar) in microtissues. Cell contractility and
      microtissue geometry cooperated to remodel these two populations, resulting in
      spatial gradients in Fn conformation. Together, these results highlight an
      important spatio-temporal interplay between two prominent extracellular matrix
      (ECM) molecules (Fn and collagen) and cellular traction forces, and will have
      implications for future studies of the force-mediated remodeling events that
      occur within collagen scaffolds either in 3D in vitro models or within surgical
      implants in vivo.

PMID- 22961410
TI  - Diastolic heart failure: a confusing concept.
AB  - Descriptions of the pathophysiology of heart failure have gone through a
      substantial evolution in the last 50 years. It is now recognised that heart
      failure can occur in the presence and also in the absence of a reduction in left
      ventricular function. In the former situation, this classically has been
      described to lead to hypotension and secondary salt and volume retention by the
      kidneys, further aggravating cardiac function. In the latter, this has been
      described to lead to pulmonary congestion because of impaired cardiac diastolic
      filling. These concepts have further evolved in the discrimination of 'acute
      vascular' versus 'acute congestive' heart failure. The current paper builds the
      argument from numerous smaller observational studies that irrespective of the
      clinical presentation of heart failure, fluid congestion is the key. If left
      ventricular function is preserved, fluid retention is probably due to the
      inability of damaged kidneys to excrete the large amounts of salt ingested with
      modern diet. In the extreme of end-stage renal disease requiring haemodialysis,
      heart failure is frequent, but can be prevented almost entirely by strict volume
      control. Unfortunately, the absence of systematic studies describing fluid
      volumes and renal haemodynamic and reabsorptive function in patients with acute
      heart failure precludes the final proof of our concept. This paper therefore is a
      strong call for mechanistic research in this area.

PMID- 22961411
TI  - KlucelTM EF and ELF polymers for immediate-release oral dosage forms prepared by
      melt extrusion technology.
AB  - The objective of this research work was to evaluate KlucelTM
      hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as
      well as to address some of the disadvantages associated with solid dispersions.
      Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with
      poor solubility, was utilized as a model compound. Preliminary thermal studies
      were performed to confirm formation of a solid solution/dispersion of KPR in HPC
      matrix and also to establish processing conditions for hot-melt extrusion.
      Extrudates pelletized and filled into capsules exhibited a carrier-dependent
      release with ELF polymer exhibiting a faster release. Tablets compressed from
      milled extrudates exhibited rapid release owing to the increased surface area of
      the milled extrudate. Addition of mannitol (MNT) further enhanced the release by
      forming micro-pores and increasing the porosity of the extrudates. An optimized
      tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90%
      release in 15 min similar to a commercial capsule formulation. HPC polymers are
      non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent
      solubilization and can be used to enhance solubility or dissolution rate of
      poorly soluble drugs. Dissolution/release rate could be tailored for rapid
      release applications by selecting a suitable HPC polymer and altering the final
      dosage form. The release obtained from pellets was carrier-dependent and not drug
      dependent, and hence, such a system can be effectively utilized to address
      solubility or precipitation issues with poorly soluble drugs in the
      gastrointestinal environment.

PMID- 22961412
TI  - Effect of formulation conditions on hypromellose performance properties in films
      used for capsules and tablet coatings.
AB  - This study investigated the effects of polymer dispersion and hydration
      conditions on hypromellose (HPMC) film properties, such as strength, oxygen
      permeability, water vapor transmission, clarity, and haze. The focus of the study
      was to build a better understanding of the impact that changes to HPMC dispersion
      and hydration conditions have on performance properties of the resulting films.
      This understanding could potentially lead to more flexible formulation guidelines
      for formulators. Films of HPMC 2906 (USP) were produced from aqueous solutions
      prepared using various formulation conditions. Results showed that tensile
      properties and oxygen permeability were not significantly affected by the
      variables used. The differences observed in water vapor transmission are unlikely
      to affect practical application of the material. However, the differences
      observed in clarity and haze at 50 degrees C hydration temperature could affect
      the appearance of a capsule or coated tablet. Several methods were used to
      determine whether loss of optical properties was due to surface phenomena or bulk
      defects within a film. Results indicated that the cloudy appearance was primarily
      due to surface roughness. Based on this information, there is some flexibility in
      formulation conditions; however, hydration temperatures greater than 25 degrees C
      are not recommended.

PMID- 22961414
TI  - [Improving patient safety in perioperative care for major surgeries].
AB  - The Helsinki Declaration was created and signed by the European Board of
      Anaesthesiology (EBA) and the European Society of Anaesthesiology (ESA). It was
      initiated in June 2010, and it implies a European consensus on those medical
      practices which improve patient safety and provide higher quality perioperative
      care. Authors focus on four elements of this initiative, which can be easily
      implemented, and provide almost instant benefit: use of preoperative checklist,
      prevention of perioperative infections, goal-directed fluid therapy and
      perioperative nutrition. The literature review emphasizes that well organized
      perioperative care plays the most important role in improving patient safety.

PMID- 22961413
TI  - A drug-in-adhesive matrix based on thermoplastic elastomer: evaluation of
      percutaneous absorption, adhesion, and skin irritation.
AB  - A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic
      elastomer, styrene-isoprene-styrene (SIS) block copolymer, in combination with
      tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin
      was selected as the model drug. The drug percutaneous absorption, adhesion
      properties, and skin irritation were investigated. The results suggested that the
      diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous
      absorption. [SI] content in SIS and SIS proportions put important effects on drug
      penetration and adhesion properties. The chemical enhancers had strong
      interactions with the matrix and gave small effect on enhancement of drug skin
      permeation. The in vivo absorption of samples showed low drug plasma peaks and a
      steady and constant plasma level for a long period. These results suggested that
      the possible side effects of drug were attenuated, and the pharmacological
      effects were enhanced with an extended therapeutic period after application of
      SIS matrix. The significant differences in pharmacokinetic parameters produced by
      different formulations demonstrated the influences of SIS copolymer on drug
      penetrability. Furthermore, the result of skin toxicity test showed that no skin
      irritation occurred in guinea pig skin after transdermal administration of
      formulations.

PMID- 22961415
TI  - [Urgent endoscopic retrograde cholangio-pancreatography: to whom, when and how to
      perform?].
AB  - Although the effectivity of an urgent endoscopic retrograde cholangio
      pancreatography was documented, some aspects relating to this method are still
      debated. Timing of this procedure has not been established yet. Indications for
      urgent endoscopic retrograde cholangio-pancreatography with stone extraction from
      the common bile duct in patients with biliary pancreatitis remains controversial.
      Biliary decompression and drainage is the cornerstone of acute cholangitis
      treatment. The timing of endoscopic retrograde cholangio-pancreatography should
      be based on the grade of the severity of the disease. Using endoscopic retrograde
      cholangio-pancreatography, the accurate diagnosis and treatment of bile leaks in
      a timely manner is imperative to limit associated morbidity and mortality.
      Difficulty in cannulating the common bile duct is one of the main risk factors
      for pancreatitis occurring after the procedure. Alternative techniques to
      facilitate difficult cannulation are discussed. Organized training and
      introduction of objective measures of the investigator's competence are
      emphasized to improve the performance of the procedure in Hungary.

PMID- 22961416
TI  - [Clinical presentation and hospital outcome of patients with ST-elevation
      myocardial infarction -- Hungarian Myocardial Infarction Registry data].
AB  - INTRODUCTION: There are only very few data on gender differences in patients with
      ST-elevation myocardial infarction. AIM: To compare the clinical data and
      prognosis of patients with ST-elevation myocardial infarction in the Hungarian
      Myocardial Infarction Registry database. PATIENTS AND METHODS: Between January 1,
      2010 and December 31, 2011 4981 patients (3038 men) were included in the
      database. RESULTS: Women were significantly older (67.7+/-13.5 vs. 60.5+/-12.5
      years; p<0.001). Hypertension, diabetes, and stroke were more frequent among
      women, whereas smoking and previous myocardial infarction were found more often
      among men. Percutaneous coronary intervention was significantly more frequently
      performed in men than in women (82.4% vs. 75.3%; p<0.001), and the time between
      the onset of pain and arrival of patients to the site of percutaneous coronary
      intervention was longer in women than in men. Hospital mortality was higher among
      women than men (7.5% vs. 4.4%; p<0.001). CONCLUSIONS: At present women have a
      poorer hospital outcome than men. By increasing the revascularization treatment
      ratio in women an improvement may be achieved in the prognosis.

PMID- 22961417
TI  - [Airport security check of medical substances used during patient repatriation].
AB  - INTRODUCTION: During airport security check of passenger luggage, hazardous items
      and substances are prohibited to be taken into the restricted safety zone of the
      airport and the aircraft. Among equipment of the medical staff escorting the
      patient, there are several devices and materials which are considered hazardous
      for security reasons. However, medical equipment and substances are indispensable
      for treating patients during the flight. AIM: The aim of the author was to
      present his experience obtained with the use of an instrument developed for
      testing liquids, aerosols and gels for security reasons. METHOD: An instrument
      based on Raman spectroscopy was used for the identification of medical
      substances. RESULTS: The results confirmed that the instrument was able to
      recognize the tested medical substances. The non-destructive testing maintained
      sample integrity and asepsis. CONCLUSIONS: The data indicate that the instrument
      has a promising utility for the identification of medical substances. It seems
      important that during repatriation medical substances should be selected not only
      on the ground of their medical necessity, but their packaging should be also
      taken into consideration. It is necessary to perform more tests on different
      medical substances used in emergency care in order to make the database of
      medical substances stored in the library of instrument more complete.

PMID- 22961418
TI  - [A diabetic patient with asymptomatic multiple arterial disease].
AB  - The authors present the case of a 73-year-old diabetic woman who was referred to
      hospital because of the suspicion of lower limb peripheral arterial stenosis.
      During evaluations signs of the subclavian artery occlusion were found. In
      addition to diabetes, the patient had several risk factors revealed by medical
      history. Subclavian artery occlusion was solved by angiography guided stenting,
      and angiography also showed the presence of abnormalities in renal arteries. This
      case draws the attention to the importance of screening old diabetic patients for
      arterial stenosis and the importance of accurate risk factor assessment.

PMID- 22961420
TI  - Growth and characterization of Escherichia coli DH5alpha biofilm on concrete
      surfaces as a protective layer against microbiologically influenced concrete
      deterioration (MICD).
AB  - Biofilms of selected bacteria strains were previously used on metal coupons as a
      protective layer against microbiologically influenced corrosion of metals. Unlike
      metal surfaces, concrete surfaces present a hostile environment for growing a
      protective biofilm. The main objective of this research was to investigate
      whether a beneficial biofilm can be successfully grown on mortar surfaces.
      Escherichia coli DH5alpha biofilm was grown on mortar surfaces for 8 days, and
      the structure and characteristics of the biofilm were studied using advanced
      microscopy techniques such as scanning electron microscopy and confocal laser
      scanning microscopy in combination with fluorescence in situ hybridization,
      live/dead, extracellular polymer staining, ATP analysis, and membrane filtration.
      A biofilm layer with a varying thickness of 20-40 MUm was observed on the mortar
      surface. The distribution of live and dead bacteria and extracellular polymers
      varied with depth. The density of the live population near the mortar surface was
      the lowest. The bacteria reached their highest density at three fourths of the
      biofilm depth and then decreased again near the biofilm-liquid interface.
      Overall, the results indicated a healthy biofilm growth in the chosen growth
      period of 8 days, and it is expected that longer growth periods would lead to
      formation of a more resistant biofilm with more coverage of mortar surfaces.

PMID- 22961421
TI  - DNA damage kinetics and apoptosis in ivermectin-treated Chinese hamster ovary
      cells.
AB  - A comet assay was used to analyze DNA damage kinetics in Chinese hamster ovary
      (CHO-K1) cells induced by antiparasitic ivermectin (IVM) and the IVM-containing
      technical formulation Ivomec(r) (IVO; 1% IVM). Cells were treated with 50 ug ml(
      1) IVM and IVO for 80 min, washed and re-incubated in antiparasiticide-free
      medium for 0-24 h until assayed using the single-cell gel electrophoresis assay
      (SCGE). Cell viability remained unchanged up to 3 h of incubation. After 6 h of
      treatment, cell survival decreased up to 75% and 79% in IVM- and IVO-treated
      cultures, respectively, remaining unchanged within 12-24 h after treatment. For
      both anthelmintics, biphasic behavior in DNA damage occurred during the
      incubation time. A time-dependent increase of IVM- and IVO-induced DNA damage was
      observed within 0 to 3 h after pulse treatment, revealed by a progressive
      decrease of undamaged cells and an increase in slightly damaged and damaged
      cells. Finally, a time-dependent decrease in IVM- and IVO-induced DNA damage was
      revealed by a progressive decrease of slightly damaged cells and the absence of
      damaged cells simultaneously with an increase in the frequency of undamaged cells
      during the final 18 h of incubation. Flow cytometry analysis revealed that both
      compounds are able to induce a marked increase in early and late apoptosis. Based
      on our observations, we could conclude that the decrease in DNA lesions is mostly
      related to IVM-induced cytotoxicity rather than attributable to a repair process.

PMID- 22961422
TI  - BAX 855, a PEGylated rFVIII product with prolonged half-life. Development,
      functional and structural characterisation.
AB  - A longer acting recombinant FVIII is expected to serve patients' demand for a
      more convenient prophylactic therapy. We have developed BAX 855, a PEGylated form
      of Baxter's rFVIII product ADVATETM based on the ADVATETM manufacturing process.
      The conjugation process for preparing BAX 855 uses a novel PEG reagent. The
      production process was adjusted to yield a rFVIII conjugate with a low PEGylation
      degree of about 2 moles PEG per FVIII molecule. This optimised modification
      degree resulted in an improved PK profile for rFVIII without compromising its
      specific activity. PEGylation sites were identified by employing various HPLC-
      and MS-based methods. These studies not only indicated that about 60% of the PEG
      chains are localised to the B-domain, which is cleaved off upon physiological
      activation during the coagulation process, but also demonstrated an excellent lot
      to lot consistency with regard to PEGylation site distribution. Detailed
      biochemical characterization further showed that PEGylated FVIII retained all the
      physiological functions of the FVIII molecule with the exception of binding to
      the LRP clearance receptor which was reduced for BAX 855 compared to ADVATETM.
      This might provide an explanation for the prolonged circulation time of BAX 855
      as reduced receptor binding might slow-down clearance. Preclinical studies showed
      improved pharmacokinetic behaviour and clinically relevant prolonged efficacy
      compared to ADVATETM without any signs of toxicity or elevated immunogenicity.
      The comprehensive preclinical data package formed the basis for approval of the
      phase 1 clinical study by European authorities which started in 2011.

PMID- 22961423
TI  - New surgical algorithm for femoral head split fractures with anatomical study.
AB  - BACKGROUND: The femoral head split fracture line is usually located in the
      anterior-inferior portion of the head. Proper fixation is difficult using the
      conventional approach without tenotomy, and thus, the authors sought to devise an
      effective, safe, fixation approach for the most common type of head fracture.
      METHODS: Anatomical dissection of 80 femoral triangles was performed. The authors
      evaluated the locations of femoral nerves, vessels, and branches within femoral
      triangles. On the basis of these observations we used a new anterior approach via
      the non-dangerous lateral space of the femoral triangle. This approach was
      applied to 12 femoral head split fractures treated from 2002 to 2009. RESULTS: A
      safe area was found within the femoral triangle at the proximal 17.5-32.5 % of
      the full length of the rectus femoris. In Brumback type 1A and 2A cases, screws
      were inserted at right angles relative to the fracture plane through the space.
      CONCLUSIONS: This study contributes by providing a new technique for femoral head
      split fractures. This anterior approach using the lateral aspect of femoral
      triangle provided excellent and good results for Brumback type 1A and 2A femoral
      head split fractures. On the basis of this study, we produced new treatment
      algorithm for femoral head split fracture.

PMID- 22961424
TI  - Physical performance tests are useful for evaluating and monitoring the severity
      of locomotive syndrome.
AB  - BACKGROUND: The concept of the locomotive syndrome (LS), first proposed in Japan
      in 2007, has become widely accepted, and the 25-question Geriatric Locomotive
      Function Scale (GLFS-25), a quantitative, evidence-based diagnostic tool for LS,
      has been developed. However, the association between the GLFS-25 score and the
      outcome of physical capacity tests has never been investigated. Furthermore,
      which physical tests are good indices for evaluating and monitoring the severity
      of locomotive syndrome have not been identified. In addition, the impact of knee
      and low back pain on locomotive syndrome is unclear. The purpose of this study is
      to confirm the validity of GLFS-25 by demonstrating its significant correlation
      with the outcome of physical function tests and to determine which tests are good
      indicators for monitoring the severity of LS. The secondary aim of the project is
      to investigate how much influence knee and low back pain may have on the LS of
      the middle-aged and elderly. METHODS: A total of 358 subjects were drawn from a
      general health checkup in a rural area of Japan. We measured back muscle
      strength, grip strength, one-leg standing time with eyes open, 10-m gait time,
      timed up-and-go test, maximum stride, functional reach, height, weight, % body
      fat and bone mineral density, and we obtained a visual analog scale of low back
      pain and knee pain. The degree of the locomotive syndrome was evaluated using the
      GLFS-25. Associations of all the variables with the GLFS-25 score were analyzed
      using both univariate and multivariate analyses. RESULTS: The GLFS-25 score was
      significantly higher in females than in males in both the total and in the age
      older than 60 years groups. The GLFS-25 score showed a significant positive
      correlation with age (r = 0.360), knee pain (r = 0.576), low back pain (r =
      0.526), timed up-and-go test (r = 0.688) and 10-m gait time (r = 0.634), and it
      showed a significant negative correlation with one-leg standing time with eyes
      open (r = -0.458), maximum stride (r = -0.408), functional reach test (r = 
      0.380), back muscle strength (r = -0.364) and grip strength (r = -0.280).
      Multiple regression analysis indicated that knee pain (beta = 0.282), low back
      pain (beta = 0.304), one-leg standing time (beta = -0.116), timed up-and-go test
      (beta = -0.319) and back muscle strength (beta = -0.090) were significantly
      associated with the GLFS-25 score. Grip strength (beta = -0.99) was a good
      substitute for back muscle strength in the multiple regression analysis.
      CONCLUSIONS: We confirmed the validity of GLFS-25 by demonstrating a significant
      correlation and association of its score with the outcome of a series of
      functional performance tests. One-leg standing time with eyes open, timed up-and
      go test and grip strength proved to be easy, reliable and safe performance tests
      to evaluate and monitor an individual's severity of LS as a complement to the
      GLFS-25. We also proved that knee and low back pain significantly impact the
      degree of LS.

PMID- 22961425
TI  - Remodeling of angulation deformities in diaphyseal femoral fracture in children.
AB  - BACKGROUND: The purpose of this study was to reconsider the factors influencing
      the remodeling effects in diaphyseal femoral fractures in children based on
      radiological results. PATIENTS AND METHOD: We reviewed 39 patients with more than
      a 5 degrees  residual angulation deformity at the fracture site on
      anteroposterior and/or lateral views at the primary healing stage. The average
      follow-up period was 30.4 months. Angulation deformity was measured on plain
      radiographs both at the primary healing stage and the final follow-up. The
      correction rate (A - B/A * 100, A angulation deformities at the primary healing,
      B the angulation at the final follow-up) between at the primary healing stage and
      final follow-up was analyzed in terms of age at injury (0-5, 6-9, and >=10
      years), fracture site (proximal one third, middle one third, and distal one
      third) and direction of the deformities (coronal and sagittal planes). RESULT:
      The remodeling effect significantly appeared on the coronal plane (correction
      rate 66.7 %) rather than on the sagittal plane (correction rate 31.6 %) in the 0-
      to 5-year age group (P < 0.05). There was a statistically significant difference
      in the correction rate between the 0- to 5-year age group (66.7 %) and the 6- to
      9-year group (30.6 %) on the coronal plane (P < 0.05), with no significance
      between any other two groups on both planes. No statistical difference of
      remodeling effect appeared among the three fracture sites. The average leg-length
      discrepancy was 4.7 mm longer. CONCLUSION: We suggest that a patient <=5 years at
      injury could expect more sufficient remodeling on the coronal plane compared with
      the other age groups on both planes. However, a patient >5 years at injury should
      be encouraged to undergo the maximum possible correction of the angulation
      deformity at the initial treatment. Surgical intervention might be considered for
      that purpose.

PMID- 22961426
TI  - Letter regarding "Effects of botulinum toxin A on fracture healing in rats: an
      experimental study".

PMID- 22961427
TI  - The influence of pH on phosphatidylethanolamine monolayer at the air/aqueous
      solution interface.
AB  - The dependence of the interfacial tension of a phosphatidylethanolamine (PE)
      monolayer on the pH of the aqueous solution has been studied. A theoretical
      equation is derived to describe this dependence. A simple model of the influence
      of pH on the phosphatidylethanolamine monolayer at the air/hydrophobic chains of
      PE is presented. The contributions of additive phosphatidylethanolamine forms
      (both interfacial tension values and molecular area values) depend on pH. The
      interfacial tension values and the molecular area values for PEH(+) and PEOH(-)
      forms of phosphatidylethanolamine were calculated. The assumed model was verified
      experimentally. The experimental results agreed with those derived from the
      theoretical equation in a whole range of pH values.

PMID- 22961428
TI  - Immobilization of the alpha-amylase of Bacillus amyloliquifaciens TSWK1-1 for the
      improved biocatalytic properties and solvent tolerance.
AB  - The alpha-amylase of Bacillus amyloliquifaciens TSWK1-1 (GenBank Number,
      GQ121033) was immobilized by various methods, including ionic binding with DEAE
      cellulose, covalent coupling with gelatin and entrapment in polyacrylamide and
      agar. The immobilization of the purified enzyme was most effective with the DEAE
      cellulose followed by gelatin, agar and polyacrylamide. The K m increased, while
      V max decreased upon immobilization on various supports. The temperature and pH
      profiles broadened, while thermostability and pH stability enhanced after
      immobilization. The immobilized enzyme exhibited greater activity in various non
      ionic surfactants, such as Tween-20, Tween-80 and Triton X-100 and ionic
      surfactant, SDS. Similarly, the enhanced stability of the immobilized alpha
      amylase in various organic solvents was among the attractive features of the
      study. The reusability of the immobilized enzyme in terms of operational
      stability was assessed. The DEAE cellulose immobilized alpha-amylase retained its
      initial activity even after 20 consequent cycles. The DEAE cellulose immobilized
      enzyme hydrolyzed starch with 27 % of efficiency. In summary, the immobilization
      of B. amyloliquifaciens TSWK1-1 alpha-amylase with DEAE cellulose appeared most
      suitable for the improved biocatalytic properties and stability.

PMID- 22961429
TI  - Human papillomavirus in oropharyngeal squamous cell carcinoma: assessing virus
      presence in normal tissue and activity in cervical metastasis.
AB  - OBJECTIVES/HYPOTHESIS: Human papillomavirus (HPV) has been established as an
      etiologic and prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC).
      HPV oncogenesis involves expression of E6/E7 oncoproteins, with downstream p53
      degradation and pRb inhibition. Although much research has focused on HPV's
      oncogenic behavior in primary OPSCC, minimal information exists about HPV in
      adjacent normal and metastatic tissue. STUDY DESIGN: Retrospective cohort study
      METHODS: Patient-matched tumor, normal, and metastatic tissue was gathered from
      42 OPSCC patients and tested with real-time quantitative polymerase chain
      reaction (RT-qPCR), in situ hybridization (ISH), and immunohistochemistry (IHC).
      RT-qPCR was performed using total RNA from fresh-frozen tissues and primers for
      HPV16 E6, E7, and p16 transcripts. HPV ISH was performed to detect the presence
      of HPV DNA and IHC to detect p16 protein. RESULTS: Primary tumor, adjacent normal
      tissue, and tumor metastasis from 17 OPSCC patients were analyzed. When comparing
      the presence of HPV16 DNA in tumor, metastatic, and normal tissue by ISH, perfect
      correlation is found at all subsites (P < .0001). However, active infections
      determined by HPV16 E6 and E7 expression using quantitative polymerase chain
      reaction or p16 detection by IHC, were present only in primary and metastatic
      tissue (P = .0012, E6; P = .02, E7). No such correlation was found in normal
      tissue when compared to primary or metastatic tissue. CONCLUSIONS: There is a
      clear pattern of active HPV expression that correlates to disease course. In HPV
      positive patients, all sites including primary, metastatic, and normal tissues
      are DNA positive. Transcriptionally active infections were detected in primary
      and metastatic tissues, whereas normal tissues appear to have latent infections.

PMID- 22961430
TI  - Ureteral cancer in a duplicated ureter.

PMID- 22961431
TI  - Proximal interruption of the pulmonary artery.

PMID- 22961432
TI  - An unusual case of heart failure.

PMID- 22961434
TI  - Facile assembly of indeno[1,2-c]chromenes via a palladium-catalyzed reaction of 2
      alkynylhalobenzene.
AB  - 2-Alkynylhalobenzene reacts with 2-alkynylphenol in the presence of a palladium
      catalyst, leading to indeno[1,2-c]chromenes in good to excellent yields.
      Furthermore, the scaffold of indeno[1,2-c]chromene could be constructed via a
      palladium-catalyzed reaction of 2-alkynylbromobenzene with water, in which four
      bonds are formed with high efficiency.

PMID- 22961433
TI  - Predictive value of vascular endothelial growth factor overexpression in early
      relapse of colorectal cancer patients after curative resection.
AB  - BACKGROUND: Preclinical and clinical studies have indicated that vascular
      endothelial growth factor (VEGF) is the predominant angiogenic factor. Recently,
      there was a consistent trend of poorer survival rates in colorectal cancer (CRC)
      patients of earlier relapse. The purpose of this study was to investigate novel
      predictors of early relapse in stage I-III CRC and further to determine their
      correlation with disease outcomes. MATERIALS AND METHODS: We retrospectively
      analyzed clinicopathological features and VEGF expression by immunohistochemical
      staining in 100 stage I-III CRC patients undergoing curative resection to
      identify predictors of postoperative early relapse. RESULTS: Among 100 patients,
      40 patients were classified into early relapse group, and 60 patients were
      categorized into non-early relapse group. A multivariate logistic regression
      analysis showed that vascular invasion (P = 0.048), perineural invasion (P =
      0.042), VEGF overexpression (P = 0.023), and high postoperative carcinoembryonic
      antigen (CEA) levels (P = 0.004) were independent predictors of early relapse.
      Additionally, we found that with more predictors such as the combined incidence
      of vascular invasion, perineural invasion, VEGF overexpression, and postoperative
      CEA levels are involved, the incidence of early postoperative relapse increases.
      Moreover, VEGF overexpression predicted not only early postoperative relapse but
      also disease-free survival (P < 0.001) and overall survival (P = 0.002).
      CONCLUSIONS: This study suggests that VEGF overexpression is an important
      predictor of early postoperative relapse in patients with stage I-III CRC and may
      help identify patients who would benefit from intensive follow-up and therapeutic
      programs.

PMID- 22961435
TI  - Discordance between pain and radiographic severity in knee osteoarthritis:
      findings from quantitative sensory testing of central sensitization.
AB  - OBJECTIVE: Radiographic measures of the pathologic changes of knee osteoarthritis
      (OA) have shown modest associations with clinical pain. We sought to evaluate
      possible differences in quantitative sensory testing (QST) results and
      psychosocial distress profiles between knee OA patients with discordant versus
      congruent clinical pain reports relative to radiographic severity measures.
      METHODS: A total of 113 participants (66.7% women; mean +/- SD age 61.05 +/- 8.93
      years) with knee OA participated in the study. Radiographic evidence of joint
      pathology was graded according to the Kellgren/Lawrence scale. Central
      sensitization was indexed through quantitative sensory testing, including heat
      and pressure-pain thresholds, tonic suprathreshold pain (cold pressor test), and
      repeated phasic suprathreshold mechanical and thermal pain. Subgroups were
      constructed by dichotomizing clinical knee pain scores (median split) and knee OA
      grade scores (grades 1-2 versus 3-4), resulting in 4 groups: low pain/low knee OA
      grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA
      grade (n = 27), and high pain/low knee OA grade (n = 30). RESULTS: Multivariate
      analyses revealed significantly heightened pain sensitivity in the high pain/low
      knee OA grade group, while the low pain/high knee OA grade group was less pain
      sensitive. Group differences remained significant after adjusting for differences
      on psychosocial measures, as well as age, sex, and race. CONCLUSION: The results
      suggest that central sensitization in knee OA is especially apparent among
      patients with reports of high levels of clinical pain in the absence of moderate
      to-severe radiographic evidence of pathologic changes of knee OA.

PMID- 22961436
TI  - Sleep quality of mechanically ventilated patients sedated with dexmedetomidine.
AB  - PURPOSE: Dexmedetomidine is thought to activate an endogenous pathway that
      naturally promotes non-rapid eye movement (NREM) sleep. Dexmedetomidine may
      induce restorative sleep, that is, NREM stage 3 and 4 (slow wave sleep; SWS) or
      sleep continuity in mechanically ventilated patients. Few data have been
      published, however, on the sleep characteristics of mechanically ventilated
      patients during dexmedetomidine infusion. METHODS: We recorded polysomnography
      (PSG) for 24 h in mechanically ventilated patients sedated with dexmedetomidine.
      Dexmedetomidine (0.2-0.7 MUg/kg/h) was administered intravenously to maintain the
      Richmond Agitation-Sedation Scale between -1 and -4 only during the nighttime
      (9:00 p.m. to 6:00 a.m.). During the daytime, we interrupted the sedatives and
      analgesics unless the patient complained of discomfort. When this occurred
      midazolam or opioids were administered intermittently. Sleep stages and the
      frequency of arousal/awakening during the nighttime were analyzed using
      Rechtschaffen and Kales criteria. RESULTS: For the ten mechanically ventilated
      adult patients recruited into the study, the median total sleep time (TST) during
      the night was 4.7 h (IQR, 4.2-8.1 h), and 78 % of sleep occurred during the night
      (median 78 %, IQR: 69-88 %). Sleep architecture was exclusively NREM sleep stage
      1 (median 28.9 % of TST) and stage 2 (median 71.2 % of TST). Neither SWS (median
      0 % of TST) nor rapid eye movement (REM) sleep (median 0 % of TST) was observed.
      Median frequency of arousals/awakenings was 9.3/h (IQR, 3-19.5/h). CONCLUSIONS:
      In mechanically ventilated patients, nighttime infusion of dexmedetomidine
      preserved the day-night cycle of sleep but induced severely disturbed sleep
      architecture without evidence of SWS or REM sleep.

PMID- 22961438
TI  - Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer.
AB  - Ovarian cancer causes more deaths than any other type of female reproductive
      cancer. The development of new therapeutic approaches is required due to the low
      survival rate using routine methods. The goal of this study was to investigate
      the effect of the gene silencing of mediator complex subunit 19 (MED19) on cell
      viability and tumor growth in ovarian cancer. Immunohistochemistry was used to
      characterize the expression of MED19 in human ovarian cancer tissues. Lentivirus
      mediated RNAi was employed to downregulate endogenous MED19 expression in SKOV-3
      and HEY ovarian cancer cells. MTT assay, BrdU incorporation assay, colony
      formation assay, cell cycle analysis and tumor xenografts in nude mice were
      performed to determine the effects of MED19 silencing on cell viability and tumor
      growth in vitro and in vivo. The data showed that the expression of MED19 in
      human ovarian cancer tissues correlated with the level of tumor malignancy. The
      downregulation of MED19 in ovarian cancer cells significantly inhibited cell
      proliferation and colony formation in vitro and led to cell cycle arrest in the
      G0/G1 phase. MED19 RNAi significantly inhibited ovarian cancer tumor growth in
      engrafted nude mice. Our findings reveal that the knockdown of MED19 by
      lentivirus-mediated RNAi may be useful in the treatment of human ovarian cancer.

PMID- 22961440
TI  - VEGF over-expression in skeletal muscle induces angiogenesis by intussusception
      rather than sprouting.
AB  - Therapeutic over-expression of vascular endothelial growth factor (VEGF) can be
      used to treat ischemic conditions. However, VEGF can induce either normal or
      aberrant angiogenesis depending on its dose in the microenvironment around each
      producing cell in vivo, which limits its clinical usefulness. The goal herein was
      to determine the cellular mechanisms by which physiologic and aberrant vessels
      are induced by over-expression of different VEGF doses in adult skeletal muscle.
      We took advantage of a well-characterized cell-based platform for controlled gene
      expression in skeletal muscle. Clonal populations of retrovirally transduced
      myoblasts were implanted in limb muscles of immunodeficient mice to homogeneously
      over-express two specific VEGF(164) levels, previously shown to induce
      physiologic and therapeutic or aberrant angiogenesis, respectively. Three
      independent and complementary methods (confocal microscopy, vascular casting and
      3D-reconstruction of serial semi-thin sections) showed that, at both VEGF doses,
      angiogenesis took place without sprouting, but rather by intussusception, or
      vascular splitting. VEGF-induced endothelial proliferation without tip-cell
      formation caused an initial homogeneous enlargement of pre-existing microvessels,
      followed by the formation of intravascular transluminal pillars, hallmarks of
      intussusception. This was associated with increased flow and shear stress, which
      are potent triggers of intussusception. A similar process of enlargement without
      sprouting, followed by intussusception, was also induced by VEGF over-expression
      through a clinically relevant adenoviral gene therapy vector, without the use of
      transduced cells. Our findings indicate that VEGF over-expression, at doses that
      have been shown to induce functional benefit, induces vascular growth in skeletal
      muscle by intussusception rather than sprouting.

PMID- 22961441
TI  - Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated
      in human vascular malformations.
AB  - Despite multiple previous studies in the field of vascular anomalies, the
      mechanism(s) leading to their development, progression and maintenance has
      remained unclear. In this study, we have characterized the expression levels of
      vascular endothelial growth factors and their receptors in 33 human vascular
      anomalies. Analysis with quantitative real-time PCR and gene-specific assays
      showed higher expression of neuropilin-2 (NRP2) and VEGF-receptor-3 (VEGFR-3)
      mRNAs in vascular malformations (VascM) as compared to infantile hemangiomas
      (Hem). In addition, the expression levels of PlGF and VEGF-C mRNA were
      significantly higher in venous VascM when compared to the other VascM and Hem.
      Higher expression of NRP2 and VEGFR-3 were confirmed by immunohistochemistry. To
      further study the importance of NRP2 and VEGFR-3, endothelial cell (EC) cultures
      were established from vascular anomalies. It was found that NRP2 and VEGFR-3 mRNA
      levels were significantly higher in some of the VascM ECs as compared to human
      umbilical vein ECs which were used as control cells in the study. Furthermore,
      adenoviral delivery of soluble decoy NRP2 prevented the proliferation of ECs
      isolated from most of the vascular anomalies. Our findings suggest that NRP2
      functions as a factor maintaining the pathological vascular network in these
      anomalies. Thus, NRP2 could become a potential therapeutic target for the
      diagnosis and treatment of vascular anomalies.

PMID- 22961439
TI  - Oleic acid mitigates TNF-alpha-induced oxidative stress in rat cardiomyocytes.
AB  - Some of the effects of tumor necrosis factor alpha (TNF-alpha) are suggested to
      be mediated by oxidative stress. It has also been reported that dietary
      supplements of olive oil result in a reduction in LDL, oxidative stress, and
      blood pressure and these effects are attributed to oleic acid (OA)-a major
      component of olive oil. The objective of this study was to examine the beneficial
      effects of OA against TNF-alpha-induced oxidative stress and cardiomyocytes
      injury. Isolated cardiomyocytes from adult rat hearts were treated as follows:
      (A) control; (B) OA (50 MUM); (C) TNF-alpha (10 ng/ml); and (D) TNF-alpha + OA.
      After 4 h of the treatment, cells were assessed for oxidative stress, cellular
      damage, viability, and apoptosis. Cardiomyocytes treated with TNF-alpha showed a
      significant increase (P < 0.05) in reactive oxygen species, decrease in the
      viability of cells, and increase in creatine kinase release. All these TNF-alpha
      induced changes were prevented by OA. TNF-alpha also caused a significant
      increase in the expression of apoptotic proteins Bax, Caspase 3 and PARP
      cleavage, Bnip3, and TGF-beta , whereas OA modulated these changes. It is
      suggested that TNF-alpha induced oxidative stress mediates cardiomyocyte cell
      damage which is prevented by OA.

PMID- 22961442
TI  - Simultaneous ANAMMOX and denitrification (SAD) process in batch tests.
AB  - The occurrence of simultaneous anaerobic ammonia oxidation and nitrate reduction
      (SAD) processes by enrichment culture in the presence of glucose were clarified
      in batch tests. Nitrate conversion and the formation of interim by-products were
      investigated under autotrophic and mixotrophic conditions. Eventually, the
      nitrite was fully consumed and co-occurred with ammonia oxidation. The effect of
      penicillin G and methanol on the SAD process was also investigated. Methanol
      addition led to complete loss of ANAMMOX activity at concentrations as low as 1
      mM. Penicillin G has little effect on the SAD process. Scanning electron
      microscopy (SEM) observation and denaturing gradient gel electrophoresis (DGGE)
      analysis revealed that ANAMMOX bacteria and co-existing bacteria are responsible
      for the SAD process. In conclusion, this study indicates that the ratio of
      nitrogen to organic carbon, and the cooperation and competition between microbes
      can affect the dynamics of this process. It has a potential application to remove
      ammonia and nitrate in the presence of organic matter by the SAD process.

PMID- 22961443
TI  - Carnosic acid is an efflux pumps modulator by dissipation of the membrane
      potential in Enterococcus faecalis and Staphylococcus aureus.
AB  - Bacterial resistance to antibiotics has become a serious problem of public
      health. Along with the controlled permeability by the cell-wall, active efflux
      systems can provide resistance by extruding antibiotics. Carnosic acid is capable
      to potentiate the antimicrobial activity of several antibiotics. However, the
      underlying molecular mechanism governing this effect remains unclear. The present
      study aims to investigate the effect of carnosic acid on the transport of
      ethidium bromide, on the permeability or the membrane potential in Enterococcus
      faecalis and Staphylococcus aureus. By using fluorimetric assays it was
      demonstrated that in E. faecalis, carnosic acid is a modulator of the uptake and
      efflux of ethidium bromide which does not induce cell membrane permeabilization
      phenomena. Such effect was sensitive to the inhibition caused by both the proton
      motive force carbonyl cyanide m-chlorophenylhydrazone and the calcium antagonist
      verapamil, but not to vanadate, an ATPase inhibitor. In this work it was
      demonstrated, for the first time, that the activity of carnosic acid on the
      uptake/efflux of ethidium bromide is correlated with its capacity to change the
      membrane potential gradient in S. aureus and E. faecalis. In conclusion, carnosic
      acid is a natural compound, structurally unrelated to known antibiotics, which
      can function as an efflux pump modulator by dissipation of the membrane
      potential. Therefore, carnosic acid would be a good candidate to be employed as a
      novel therapeutic agent to be used in combination therapies against drug
      resistant enterococci and S. aureus infections.

PMID- 22961444
TI  - Patterns of persistent genital human papillomavirus infection among women
      worldwide: a literature review and meta-analysis.
AB  - Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest
      risk factor for high-grade cervical precancer. We performed a systematic review
      and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of
      Science were searched through January 1, 2010 for articles estimating HPV
      persistence or duration of detection. Descriptive and meta-regression techniques
      were used to summarize variability and the influence of study definitions and
      characteristics on duration and persistence of cervical HPV infections in women.
      Among 86 studies providing data on over 100,000 women, 73% defined persistence as
      HPV positivity at a minimum of two time points. Persistence varied notably across
      studies and was largely mediated by study region and HPV type, with HPV-16, 31,
      33 and 52 being most persistent. Weighted median duration of any-HPV detection
      was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4
      months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months).
      Among populations of HPV-positive women with normal cytology, the median duration
      of any-HPV detection was 11.5 and HR-HPV detection was 10.9 months. In
      conclusion, we estimated that approximately half of HPV infections persist past 6
      to 12 months. Repeat HPV testing at 12-month intervals could identify women at
      increased risk of high-grade cervical precancer due to persistent HPV infections.

PMID- 22961445
TI  - A European multicentre PET study of fibrillar amyloid in Alzheimer's disease.
AB  - PURPOSE: Amyloid PET tracers have been developed for in vivo detection of brain
      fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early
      biomarker in AD the amyloid PET tracers need to be analysed in multicentre
      clinical studies. METHODS: In this study 238 [(11)C]Pittsburgh compound-B (PIB)
      datasets from five different European centres were pooled. Of these 238 datasets,
      18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically
      diagnosed AD (mean age 69 +/- 8 years), 72 patients with mild cognitive
      impairment (MCI; mean age 67.5 +/- 8 years) and 51 healthy controls (mean age
      67.4 +/- 6 years) available for analysis. Of the MCI patients, 64 were
      longitudinally followed for 28 +/- 15 months. Most participants (175 out of 220)
      were also tested for apolipoprotein E (ApoE) genotype. RESULTS: [(11)C]PIB
      retention in the neocortical and subcortical brain regions was significantly
      higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB
      retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB
      positive and 36 % MCI PIB-negative), which was significantly different the
      pattern in both the AD patients and controls. Higher [(11)C]PIB retention was
      observed in MCI ApoE epsilon4 carriers compared to non-ApoE epsilon4 carriers (p
      < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up
      while none of the MCI PIB-negative patients converted. CONCLUSION: This study
      demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical
      fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI
      PIB-positive patients showed more severe memory impairment than MCI PIB-negative
      patients and progressed to AD at an estimated rate of 25 % per year. None of the
      MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 %
      negative predictive value for progression to AD. This supports the notion that
      PIB-positive scans in MCI patients are an indicator of prodromal AD.

PMID- 22961446
TI  - [Morbidity and mortality of patients with haemophilia in Germany--update
      2010/2011].
AB  - Since 1982 an annual multicentric survey regarding the epidemiology of patients
      suffering of haemophilia is performed with support of haemophilia treating
      centres of any size. Again, the actual compilation is resting upon a broad
      database returning to over 30 years of inquiry well representing both the actual
      and retrospective status of mortality. Prompted was exclusively information about
      patients with haemophilia A, B and von Willebrand disease. In particular
      anonymous data concerning the preceeding 12 months about number of treated
      patients, type and severity of illness, HIV-status and detailed information about
      causes of death was inquired. This data was merged with existing data and
      analysed statistically. In the 2009/2010 survey, a total number of 9448 patients
      with bleeding disorders have been reported from 47 participating centres. Despite
      mortality from HIV in patients with haemophilia is keeping on decreasing, HIV
      still remains an important factor as an HIV/HCV coinfection seems to increase
      risk of progression of severe liver disease. In the actual investigation the
      findings of the foundation "Humanitare Hilfe fur durch Blutprodukte HIV
      infizierte Personen" were compared for the first time to our data. Time trends
      were visualised with a moving average. Our investigation has a smaller number of
      deceased patients, but contains consistent data.

PMID- 22961447
TI  - Pyrroloquinoline quinone and a quinoprotein kinase support gamma-radiation
      resistance in Deinococcus radiodurans and regulate gene expression.
AB  - Deinococcus radiodurans is known for its extraordinary resistance to various DNA
      damaging agents including gamma-radiation and desiccation. The pqqE:cat and
      Deltadr2518 mutants making these cells devoid of pyrroloquinoline quinone (PQQ)
      and a PQQ inducible Ser/Thr protein kinase, respectively, became sensitive to
      gamma-radiation. Transcriptome analysis of these mutants showed differential
      expression of the genes including those play roles in oxidative stress tolerance
      and (DSB) repair in D. radiodurans and in genome maintenance and stress response
      in other bacteria. Escherichia coli cells expressing DR2518 and PQQ showed
      improved resistance to gamma-radiation, which increased further when both DR2518
      and PQQ were present together. Although, profiles of genes getting affected in
      these mutants were different, there were still a few common genes showing similar
      expression trends in both the mutants and some others as reported earlier in oxyR
      and pprI mutant of this bacterium. These results suggested that PQQ and DR2518
      have independent roles in gamma-radiation resistance of D. radiodurans but their
      co-existence improves radioresistance further, possibly by regulating
      differential expression of the genes important for bacterial response to
      oxidative stress and DNA damage.

PMID- 22961448
TI  - Cognitive or cosmetic dysfunction?

PMID- 22961450
TI  - Derivative scores from site accessibility and ranking of miRNA target
      predictions.
AB  - In the present study, we define derivative scoring functions from PITA and
      STarMir predictions. The scoring functions are evaluated for up to five selected
      miRNAs with a relatively large number of validated targets reported by TarBase
      and miRecords. The average ranking of validated targets returned by PITA and
      STarMir is compared to the average ranking produced by the new derivatives
      scores. We obtain an average improvement of 13.6% (STD~5.7%) relative to the
      average ranking of validated targets produced by PITA and STarMir.

PMID- 22961451
TI  - Identifying cancer highly-expressed membrane receptors for targeted drug
      delivery.
AB  - Currently, the accompanying side effects of anti-cancer drugs owing to incorrect
      delivery to normal tissues should be reduced. We present a database (MRTDD) with
      identified cancer highly-expressed membrane receptors (CHMRs) which can be used
      in targeted drug delivery. To evaluate the probability of occurrence of incorrect
      delivery, we calculate tissue index for each CHMR and expect to identify good
      candidates. The information provided includes: (1) genomic annotations; (2) gene
      expression profiles of membrane receptors in cancer tissue vs. corresponding
      normal tissue, normal tissues of body and cancer cell-lines; (3) available
      antibody services of manufacturers. MRTDD is available at
      http://mrtdd.mbc.nctu.edu.tw/.

PMID- 22961449
TI  - A network-based maximum link approach towards MS identifies potentially important
      roles for undetected ARRB1/2 and ACTB in liver cancer progression.
AB  - Hepatocellular Carcinoma (HCC) ranks among the deadliest of cancers and has a
      complex etiology. Proteomics analysis using iTRAQ provides a direct way to
      analyse perturbations in protein expression during HCC progression from early- to
      late-stage but suffers from consistency and coverage issues. Appropriate use of
      network-based analytical methods can help to overcome these issues. We built an
      integrated and comprehensive Protein-Protein Interaction Network (PPIN) by
      merging several major databases. Additionally, the network was filtered for GO
      coherent edges. Significantly differential genes (seeds) were selected from iTRAQ
      data and mapped onto this network. Undetected proteins linked to seeds (linked
      proteins) were identified and functionally characterised. The process of network
      cleaning provides a list of higher quality linked proteins, which are highly
      enriched for similar biological process gene ontology terms. Linked proteins are
      also enriched for known cancer genes and are linked to many well-established
      cancer processes such as apoptosis and immune response. We found that there is an
      increased propensity for known cancer genes to be found in highly linked
      proteins. Three highly-linked proteins were identified that may play an important
      role in driving HCC progression - the G-protein coupled receptor signalling
      proteins, ARRB1/2 and the structural protein beta-actin, ACTB. Interestingly,
      both ARRB proteins evaded detection in the iTRAQ screen. ACTB was not detected in
      the original dataset derived from Mascot but was found to be strongly supported
      when we re-ran analysis using another protein detection database (Paragon).
      Identification of linked proteins helps to partially overcome the coverage issue
      in shotgun proteomics analysis. The set of linked proteins are found to be
      enriched for cancer-specific processes, and more likely so if they are more
      highly linked. Additionally, a higher quality linked set is derived if network
      cleaning is performed prior. This form of network-based analysis complements the
      cluster-based approach, and can provide a larger list of proteins on which to
      perform functional analysis, as well as for biomarker identification.

PMID- 22961452
TI  - Protein complex prediction via improved verification methods using constrained
      domain-domain matching.
AB  - Identification of protein complexes within protein-protein interaction networks
      is one of the important objectives in functional genomics. Ozawa et al. proposed
      a verification method of protein complexes by introducing a structural
      constraint. In this paper, we propose an improved integer programming-based
      method based on the idea that a candidate complex should not be divided into many
      small complexes, and combination methods with maximal components and extreme
      sets. The results of computational experiments suggest that our methods
      outperform the method by Ozawa et al. We prove that the verification problems are
      NP-hard, which justifies the use of integer programming.

PMID- 22961453
TI  - Conservation of water molecules in protein binding interfaces.
AB  - The conservation of interfacial water molecules has only been studied in small
      data sets consisting of interfaces of a specific function. So far, no general
      conclusions have been drawn from large-scale analysis, due to the challenges of
      using structural alignment in large data sets. To avoid using structural
      alignment, we propose a solvated sequence method to analyse water conservation
      properties in protein interfaces. We first use water information to label the
      residues, and then align interfacial residues in a fashion similar to normal
      sequence alignment. Our results show that, for a water-contacting interfacial
      residue, substituting it into hydrophobic residues tends to desolvate the local
      area. Surprisingly, residues with short side chains also tend not to lose their
      contacting water, emphasising the role of water in shaping binding sites. Deeply
      buried water molecules are found more conserved in terms of their contacts with
      interfacial residues.

PMID- 22961454
TI  - The algorithm of equal acceptance region for detecting copy number alterations:
      applications to next-generation sequencing data.
AB  - The information of copy number alterations (gains and losses) in tumour genomes
      can be used to discovery cancer-causing genes. The estimate of copy number can be
      obtained from the estimate copy number ratio. The higher the depth of underlying
      sequencing data, the more accurate the estimate of copy number ratio. At the same
      time, the higher depth of a sequencing data used in copy number analysis, the
      more cost of data analysis. To develop a method for identifying a necessary depth
      of sequencing data for copy number analysis before test data are produced is of
      interest. In this paper, we proposed an algorithm of equal acceptance regions for
      detecting copy number ratios. This algorithm can be used to determine the depth
      of sequencing data required for copy number analysis.

PMID- 22961455
TI  - Synthesis of insulin pump controllers from safety specifications using Bayesian
      model validation.
AB  - Insulin pump controllers seek to alleviate the chronic suffering caused by
      diabetes that affects over 6% of the world population. The design of control laws
      for insulin pump controllers has been well studied. However, the parameters
      involved in the control law are difficult to synthesize. Traditionally, ad hoc
      approaches using animal models and random sampling have been used to construct
      these parameters. We suggest a synthesis algorithm that uses Bayesian statistical
      model validation to reduce the number of simulations needed. We apply this
      algorithm to the problem of insulin pump controller synthesis using in silico
      simulation of the glucose-insulin metabolism model.

PMID- 22961456
TI  - Employing functional interactions for characterisation and detection of sparse
      complexes from yeast PPI networks.
AB  - Over the last few years, several computational techniques have been devised to
      recover protein complexes from the protein interaction (PPI) networks of
      organisms. These techniques model 'dense' subnetworks within PPI networks as
      complexes. However, our comprehensive evaluations revealed that these techniques
      fail to reconstruct many 'gold standard' complexes that are 'sparse' in the
      networks (only 71 recovered out of 123 known yeast complexes embedded in a
      network of 9704 interactions among 1622 proteins). In this work, we propose a
      novel index called Component-Edge (CE) score to quantitatively measure the notion
      of 'complex derivability' from PPI networks. Using this index, we theoretically
      categorise complexes as 'sparse' or 'dense' with respect to a given network. We
      then devise an algorithm SPARC that selectively employs functional interactions
      to improve the CE scores of predicted complexes, and thereby elevates many of the
      'sparse' complexes to 'dense'. This empowers existing methods to detect these
      'sparse' complexes. We demonstrate that our approach is effective in
      reconstructing significantly many complexes missed previously (104 recovered out
      of the 123 known complexes or ~47% improvement). AVAILABILITY:
      http://www.comp.nus.edu.sg/leonghw/MCL-CAw/

PMID- 22961457
TI  - Discriminant analysis in pairwise kernel learning for SVM classification.
AB  - Multiple kernel learning arises when different types of kernels are employed
      simultaneously. In particular, in the situation that the data are from
      heterogeneous sources. In this study, we developed a new framework for
      determining the coefficients in learning pairwise kernels for classification in
      Support Vector Machines (SVM). The effectiveness of the proposed method was then
      demonstrated through the prediction of self-renewal and pluripotency mESCs
      stemness membership genes. It was also tested on the power of discrimination in
      DNA repair gene data. The promising formulation in learning coefficients for
      pairwise kernel learning was shown via experimental evaluation. This may provide
      a novel perspective for kernel learning in future applications.

PMID- 22961458
TI  - Stereoselective synthesis of hydroxylated 3-aminoazepanes using a multi-bond
      forming, three-step tandem process.
AB  - A multi-bond forming, three-step tandem process involving a palladium(II)
      catalysed Overman rearrangement and a ring closing metathesis reaction has been
      utilised for the efficient synthesis of a 2,3,6,7-tetrahydro-3-amidoazepine.
      Substrate directed epoxidation or dihydroxylation of this synthetic intermediate
      has allowed the diastereoselective synthesis of hydroxylated 3-aminoazepanes
      including the syn-diastereomer of the balanol core. Asymmetric synthesis of the
      2,3,6,7-tetrahydro-3-amidoazepine motif was also achieved using a chiral
      palladium(II)-catalyst during the Overman rearrangement.

PMID- 22961459
TI  - Hypobaric hypoxia and reoxygenation induce proteomic profile changes in the rat
      brain cortex.
AB  - Brain, due to its high metabolism, is severely affected by hypoxia/reoxygenation.
      In this study, cerebral cortexes from rats subjected to hypobaric hypoxia
      followed by several reoxygenation periods (0 h, 24 h, and 5 days) were compared
      with normobaric normoxic controls to identify protein-expression differences
      using proteomic approaches. Only 2-fold differences in spot abundance between
      controls and experimental groups from each reoxygenation period were considered.
      The proteins identified were grouped into categories, according to their
      similarity in function or to their involvement in the same metabolic pathway. We
      distinguished five groups: (1) glycolysis, including gamma-enolase (NSE), and
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH); (2) tricarboxylic acid cycle,
      such as aconitate hydratase (ACO2); (3) oxidative phosphorylation, like F1-ATPase
      chains alpha and beta; (4) cytoskeletal, including Spna2, alpha-tubulin, beta
      tubulin, beta-actin, and microtubule-associated protein RP/EB family member 3
      (EB3); and (5) chaperones, like heat-shock protein 72 kDa (HSP72). NSE was
      upregulated while GAPDH was downregulated, both peaking at 5 days post-hypoxia.
      ACO2 and F1-ATPase decreased in all the reoxygenation periods. Spna2 and EB3 were
      expressed neither in control nor at 0 h, but 5 days post-hypoxia new expression
      took place. The alpha- and beta-tubulin levels significantly fell at 0 h, but
      after 24 h strongly increased. Also, beta-actin and HSP72 were downregulated, and
      the last one reached the lowest level at 24 h of reoxygenation. We conclude that
      the molecular mechanisms underlying hypoxia/reoxygenation in the rat cortex might
      consist of a close relationship between energy metabolism, cytoskeleton, and
      chaperones. These findings may shed light on therapeutic targets against hypoxia
      related damage.

PMID- 22961460
TI  - Analysis of the intraimplant microflora of two-piece dental implants.
AB  - OBJECTIVE: Information about the spectrum of microorganisms in the intraimplant
      cavities of two-piece dental implants is scarce. The purpose of this study was to
      assess the intraimplant microflora of two-piece dental implants by conventional
      biochemical testing, matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF MS), and 16 s rDNA gene sequencing. MATERIALS AND
      METHODS: Ten patients (six men and four women; average age = 66.7 years; age
      range = 58-78 years) received 35 two-piece titanium implants carrying ball
      attachments. Biofilm sampling was performed with sterile microbrushes, and
      nonadherent microbial samples were obtained by injection and reuptake of
      predefined volumes of NaCl solution. The samples were cultured and analyzed by
      conventional biochemical testing, MALDI-TOF MS, and 16 s rDNA gene sequencing.
      RESULTS: Of the 103 species detected, 27 and 33 were identified only in the
      biofilm and nonadherent microbial samples, respectively. Forty-three species were
      identified in both types of samples. CONCLUSIONS: Two-piece dental implants
      harbored a broad spectrum of gram-positive and gram-negative aerobes and
      anaerobes, especially rods and cocci. CLINICAL RELEVANCE: These findings confirm
      bacterial translocation from the oral cavity to intraimplant cavities.
      Microbiological methods as used in this study are necessary to reveal the
      complete vital microflora of intraimplant cavities.

PMID- 22961461
TI  - A novel three-dimensional bone chip organ culture.
AB  - OBJECTIVES: The objective of this study was to develop a 3D bone chip organ
      culture model. We aimed to collect in vitro evidence of the ability of vital bone
      chips to promote new bone formation. MATERIALS AND METHODS: We developed a 3D in
      vitro hypoxic bone chip organ culture model. Histology of the bone chips was
      performed before and after culture and immunohistochemistry after 3-week culture.
      The 3D culture supernatants were tested for the presence of pro-angiogenic growth
      factors, TGFbeta1, GADPH, bone alkaline phosphatase, osteocalcin, osteonectin,
      osteopontin, bone sialoprotein and collagen type I. RESULTS: Histology after
      culture revealed bone chips in a matrix of fibrin remnants and a fibrous
      appearing matter. Collagen type I- and IV-positive structures were also
      identified. Cells could be seen on the surface of the bone chips, with spindle
      shaped cells bridging the bone chip particles. Pro-angiogenic growth factors and
      TGFbeta1were detected in the 3D cell culture supernatants. The transcripts for
      osteocalcin, bone sialoprotein and collagen type I were revealed only via PCR.
      CONCLUSIONS: Our results indicate that bone chips in our 3D organ culture remain
      vital and may stimulate the growth of a bone-forming matrix. CLINICAL RELEVANCE:
      The use of autogenous bone chips for oral and maxillofacial bone augmentation
      procedures is widespread in clinical practice. The rationale for this is that if
      bone chips remain vital in vivo, they could provide an environment promoting new
      bone formation through growth factors and cells. This 3D culture method is an
      essential tool for investigating the behaviour of bone chips.

PMID- 22961462
TI  - Patients' radiation dose during videofluoroscopic swallowing studies according to
      underlying characteristics.
AB  - The videofluoroscopy swallowing study (VFSS) is regarded as the gold standard in
      diagnosing and assessing swallowing disorders. The goal of this study was to
      evaluate patients' radiation dose during a VFSS and to determine the influence of
      patients' underlying characteristics on radiation exposure risk. A total of 295
      patients who underwent VFSS were included in this study. The fluoroscopy machine
      was equipped with a dose area product (DAP). The mean screening time was 4.82 +/-
      1.80 min and the mean DAP was 9.62 +/- 5.01 Gy cm(2). The mean effective dose was
      1.23 +/- 0.64 mSv. Screening time and DAP had a positive correlation (r = 0.76, P
      < 0.0001). The cerebrovascular accident (CVA) group showed higher screening time
      and DAP than the nasopharyngeal cancer (NPC) group with statistical significance.
      Patients' BMI and DAP had a positive correlation (r = 0.28, P < 0.0001), and
      height, weight, and body surface area (BSA) also showed positive correlations
      with DAP. Radiation dose during VFSS is much lower than that of a routine chest
      CT, and it would take more than 40 VFSSs annually to exceed the annual radiation
      exposure dose limit according to the mean effective radiation exposure dose of
      this study. As it is difficult to exceed the annual dose limit, we assume that
      VFSS is relatively safe in terms of its radiation exposure risk.

PMID- 22961463
TI  - Opening the black box of clinical collaboration in integrated care models for
      frail, elderly patients.
AB  - PURPOSE: The purpose of the study was to understand better the clinical
      collaboration process among primary care physicians (PCPs), case managers (CMs),
      and geriatricians in integrated models of care. METHODS: We conducted a
      qualitative study with semistructured interviews. A purposive sample of 35 PCPs,
      7 CMs, and 4 geriatricians was selected in 2 integrated models of care for frail
      elderly patients in Canada and France: System of Integrated Care for Older
      Patients of Montreal and Coordination of Care for Older Patients of Paris. Data
      were analyzed using a grounded theory approach. FINDINGS: The dynamics of the
      collaboration process develop in three phases: (1) initiating relationships, (2)
      developing real two-way collaboration, and (3) developing interdisciplinary
      teamwork. The findings suggest that CMs and geriatricians collaborated well from
      the start and throughout the care management process. Real collaboration between
      the CMs and the PCPs occurred only later and was mostly fostered by the
      interventions of the geriatricians. PCPs and geriatricians collaborated only
      occasionally. IMPLICATIONS: The findings provide information about PCPs'
      commitment to the integrated models of care, the legitimization of the CM's role
      among PCPs, and the appropriate positioning of geriatricians in such models.

PMID- 22961464
TI  - Help-seeking response to subjective memory complaints in older adults: toward a
      conceptual model.
AB  - PURPOSE: Subjective memory complaint is a term used to refer older adults who
      report memory problems. Extensive literature exists on its etiology and impact on
      long-term cognitive decline, and some physicians consider it important in the
      early detection of dementia. Despite the salient features reported by both
      patients and clinicians, few people seek formal help for this complaint, and
      little research has investigated the underlying reasons for this. The current
      study explored beliefs, attitudes, and help-seeking behaviors. DESIGN AND
      METHODS: A qualitative study was carried out comprising of 18 face-to-face in
      depth interviews. The primary aim was to compare and contrast experiences between
      people, who sought formal help (n = 9), recruited from a memory service and those
      who did not seek formal help (n = 9) recruited from a screened community
      population. RESULTS: The need for both to describe the experiences of an
      unexplored group and to develop a conceptual help-seeking model prompted the use
      of thematic framework analysis. Three themes were identified as facilitators and
      barriers to formal health service use: (a) concern, (b) causation, and (c)
      perceptions of general practitioner. We identified two further key areas central
      to shaping help-seeking responses: (a) informal help seeking and (b) alternative
      pathways to care. IMPLICATIONS: These findings suggest that there is a potential
      for modifying beliefs and attitudes towards help seeking and can inform the
      development of services and policy to facilitate help seeking and target and
      provide improved care or treatment when formal help is sought.

PMID- 22961465
TI  - Relationship between staff-reported culture change and occupancy rate and
      organizational commitment among nursing homes in South Korea.
AB  - PURPOSE: This study aims to examine culture change in nursing homes in South
      Korea and to identify the outcomes of culture change implementation. DESIGN AND
      METHODS: Data were taken from survey responses from 223 top- or mid-level staff
      among nursing homes in South Korea that were selected through a proportionate
      random-stratified sampling method from four regions nationwide. Culture change in
      nursing homes was operationalized by five person-directed care (PDC) constructs
      and three organizational environment constructs, and outcome quality was
      indicated by changes to occupancy rate and organizational commitment. RESULTS:
      After controlling for facility characteristics, the effect of staff-reported
      culture change on occupancy rate and organizational commitment was analyzed
      through the multiple-regression method. Consistent with previous research, this
      study revealed positive effects of culture change for nursing homes in South
      Korea. The study found that staff-reported culture change correlated with
      occupancy rate and organizational commitment. IMPLICATIONS: Given that culture
      change variables were significantly related to occupancy rate and organizational
      commitment, the findings of the study provide a persuasive argument that policies
      and/or programs to support culture change in nursing homes should be enhanced.
      Management-level workers in these facilities should have the skills and knowledge
      to foster more PDC and a more person-directed environment.

PMID- 22961466
TI  - Predicting desire for institutional placement among racially diverse dementia
      family caregivers: the role of quality of care.
AB  - PURPOSE: Literature on institutionalization of patients with dementia has not
      considered the role of caregivers' quality of care, which encompasses caregivers'
      exemplary care (EC) behaviors and caregivers' potentially harmful behaviors
      (PHBs) toward care recipients. This study sought to understand the role of
      quality of care in mediating between caregiving stressors and caregiver desire to
      institutionalize (DTI) a patient with dementia. DESIGN AND METHODS: A sample of
      612 family caregivers from diverse racial/ethnic backgrounds was drawn from the
      baseline data of the Resources for Enhancing Alzheimer's Caregiver Heath (REACH
      II) project. Multiple mediator models were run using Preacher and Hayes
      asymptotic and resampling strategies to assess direct and indirect effects of
      caregiver stressors (daily care bother, behavioral bother, and burden) on
      caregiver desire to institutionalize a patient with dementia. RESULTS: Overall,
      PHB was positively related to caregiver desire to institutionalize their care
      recipients. Specifically, PHB was found to mediate the relationship between
      caregiving stressors and DTI in the Caucasian and Latino groups, whereas only the
      mediation effect of EC was significant in the African American group.
      IMPLICATIONS: Caregivers' perceptions of quality of care helped explain their
      desire to institutionalize their care recipients with dementia. Including
      assessment of EC and PHB in clinical and social service settings is recommended
      for all ethnic groups. Interventions should facilitate EC behaviors among African
      American caregivers and address concerns of PHBs in Caucasian and Latino
      caregivers.

PMID- 22961467
TI  - Effects of an enhanced discharge planning intervention for hospitalized older
      adults: a randomized trial.
AB  - PURPOSE OF THE STUDY: To identify needs encountered by older adult patients after
      hospital discharge and assess the impact of a telephone transitional care
      intervention on stress, health care utilization, readmissions, and mortality.
      DESIGN AND METHODS: Older adult inpatients who met criteria for risk of post
      discharge complications were randomized at discharge through the electronic
      medical record. Intervention group participants received the telephone-based
      Enhanced Discharge Planning Program intervention that included biopsychosocial
      assessment and an individualized plan following program protocols to address
      identified transitional care needs. All patients received a follow-up call at 30
      days post discharge to assess psychosocial needs, patient and caregiver stress,
      and physician follow-up. RESULTS: 83.3% of intervention group participants
      experienced significant barriers to care. For 73.3% of this group, problems did
      not emerge until after discharge. Intervention patients were more likely than
      usual care patients to have scheduled and completed physician visits by 30 days
      post discharge. There were no differences between groups on patient or caregiver
      stress or hospital readmission. IMPLICATIONS: At-risk older adults may benefit
      from transitional care programs to ensure delivery of care as ordered and address
      unmet needs. Although patients who received the intervention were more likely to
      communicate and follow up with their physicians, the absence of impact on
      readmission suggests that more intensive efforts may be indicated to affect this
      outcome.

PMID- 22961468
TI  - Certification of deaths from diabetes mellitus and obesity in England: trends
      into the twenty-first century.
AB  - BACKGROUND: Most cases of Type 2 diabetes are attributable to excess weight and
      physical inactivity. We investigated trends in mortality based on doctors'
      certification of diabetes and obesity. METHODS: Analysis of a national data set
      of all certified causes of death, i.e. underlying cause and contributing causes
      ('mentions'), in England 1995-2010. RESULTS: Diabetes exhibited divergent trends
      for mortality based on underlying cause and mentions. Underlying cause rates were
      107.2 per million population [95% confidence interval (CI): 105.7-108.6] in 1995,
      but only 68.9/10(6) (CI: 67.9-69.9) in 2010. Mortality rates for mentions of
      diabetes were 403.1/10(6) (CI: 400.4-405.8) in 1995, increasing to 478.4/10(6)
      (CI: 475.7-481.0) in 2010. Underlying cause mortality for obesity was 3.7/10(6)
      (CI: 3.2-4.1) in 1995 and 7.5 (CI: 7.0-8.0) in 2010. The corresponding rates for
      mentions of obesity were 13.2/10(6) (CI: 12.6-13.9) and 34.5/10(6) (CI: 33.6
      35.4), respectively. 24.0% of death certificates with a mention of obesity also
      had diabetes recorded on the same certificate. CONCLUSIONS: Multiple-cause
      mortality statistics provide a more accurate picture than underlying cause of the
      total mortality burden attributed on death certificates to diabetes and obesity.
      Rates for both increased substantially: analysis by underlying cause alone would
      have missed this for diabetes.

PMID- 22961469
TI  - Mapping mental health service access: achieving equity through quality
      improvement.
AB  - BACKGROUND: Improving access to psychological therapies (IAPTs) services deliver
      evidence-based care to people with depression and anxiety. A quality improvement
      (QI) initiative was undertaken by an IAPT service to improve referrals providing
      an opportunity to evaluate equitable access. METHODS: QI methodologies were used
      by the clinical team to improve referrals to the service. The collection of geo
      coded data allowed referrals to be mapped to small geographical areas according
      to deprivation. RESULTS: A total of 6078 patients were referred to the IAPT
      service during the period of analysis and mapped to 120 unique lower super output
      areas (LSOAs). The average weekly referral rate rose from 17 during the baseline
      phase to 43 during the QI implementation phase. Spatial analysis demonstrated all
      15 of the high deprivation/low referral LSOAs were converted to high
      deprivation/high or medium referral LSOAs following the QI initiative.
      CONCLUSION: This work highlights the importance of QI in developing clinical
      services aligned to the needs of the population through the analysis of routine
      data matched to health needs. Mapping can be utilized to communicate complex
      information to inform the planning and organization of clinical service delivery
      and evaluate the progress and sustainability of QI initiatives.

PMID- 22961470
TI  - Neurotrophic effects of 7,8-dihydroxycoumarin in primary cultured rat cortical
      neurons.
AB  - OBJECTIVE: Neuronal loss in the central nervous system is central to the
      occurrence of neurodegenerative diseases. Pharmaceutical companies have devoted
      much effort to developing new drugs against such diseases, since there are
      currently no effective drugs for neurodegenerative disease treatment. Promoting
      the capacity for nerve regeneration is an ideal treatment target. The present
      study aimed to investigate the neurotrophic effects of 7,8-dihydroxycoumarin
      (DHC) or daphnetin in primary cultured rat cortical neurons. METHODS: Cortical
      neurons were identified by microtubule-associated protein 2 (MAP2)
      immunostaining. Morphological observation was used to measure the average length
      of neurite outgrowth. MTT and lactate dehydrogenase assays were used to assess
      neuronal survival. The mRNA expression of MAP2 and brain-derived neurotrophic
      factor (BDNF) was measured by RT-PCR. RESULTS: MAP2 immunostaining showed that
      most of the cultured cells were neurons. Compared with the vehicle control group,
      DHC promoted neurite outgrowth and prolonged neuronal survival time at
      concentrations ranging from 2 to 8 MUmol/L. Expression of both BDNF mRNA and MAP2
      mRNA was increased in the groups treated with 2, 4 and 8 MUmol/L DHC. CONCLUSION:
      DHC significantly increases neurite outgrowth and promotes neuronal survival in
      primary cultured rat cortical neurons. The neurotrophic effects of DHC are
      probably associated with increased BDNF expression.

PMID- 22961471
TI  - Clinical significance of detection of antibodies to fetal and adult acetylcholine
      receptors in myasthenia gravis.
AB  - OBJECTIVE: To evaluate the frequency, distribution and clinical significance of
      the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in
      patients with myasthenia gravis (MG). METHODS: AChR antibodies were detected by
      cell-based assay in the serum of ocular MG (OMG) (n = 90) and generalized MG
      (GMG) patients (n = 110). The fetal-type (2alpha: beta: gamma: delta) and adult
      type (2alpha: beta: epsilon: delta) AChR were used as antigens, and their
      relevance to disease presentation was assessed. RESULTS: The overall frequencies
      of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients
      examined, with 14 having serum specific to the AChR-Gamma subunit, and 22 to the
      AChR-epsilon subunit. The overall sensitivity when using the fetal and adult AChR
      antibodies was higher than that when using the fetal AChR antibody only (P =
      0.015). Compared with OMG patients, the mean age at disease onset and the
      positive ratio of antibodies to both isoforms of the AChR were significantly
      higher in patients who subsequently progressed to GMG. Older patients and
      patients with both anti-fetal and anti-adult AChR antibodies had a greater risk
      for developing generalized disease [odds ratio (OR), 1.03; 95% confidence
      interval (CI), 1.01-1.06 and OR, 5.09; 95% CI, 2.23-11.62]. CONCLUSION: Using
      both fetal- and adult-type AChRs as the antigens may be more sensitive than using
      either subtype. Patients with serum specific to both isoforms are at a greater
      risk of progressing to GMG. Patients with disease onset at an advanced age appear
      to have a higher frequency of GMG conversion.

PMID- 22961472
TI  - Endophilin isoforms have distinct characteristics in interactions with N-type
      Ca2+ channels and dynamin I.
AB  - OBJECTIVE: Formation of the endophilin II-Ca(2+) channel complex is Ca(2+)
      dependent in clathrin-mediated endocytosis. However, little is known about
      whether the other two endophilin isoforms have the same features. The present
      study aimed to investigate the characteristics of the interactions of all three
      isoforms with Ca(2+) channels and dynamin I. METHODS: N-type Ca(2+) channel C
      terminal fragments (NCFs) synthesized with a (3)H-leucine-labeled kit, were
      incubated with endophilin-GST fusion proteins, followed by pull-down assay.
      Results were counted on a scintillation counter. In addition, the different
      endophilin isoforms were each co-transfected with dynamin I into 293T cells,
      followed by flow cytometry and co-immunoprecipitation assay. Immunostaining was
      performed and an image analysis program was used to evaluate the overlap
      coefficient of cells expressing endophilin and dynamin I. RESULTS: All three
      isoforms interacted with NCF. Endophilins I and II demonstrated clear Ca(2+)
      dependent interactions with NCF, whereas endophilin III did not. Co
      immunoprecipitation showed that, compared to endophilin I/II, the interaction
      between endophilin III and dynamin I was significantly increased. Similar results
      were obtained from flow cytometry. Furthermore, endophilin III had a higher
      overlap coefficient with dynamin I in co-transfected 293T cells. CONCLUSION:
      Endophilin isoforms have distinct characteristics in interactions with NCF and
      dynamin I. Endophilin III binding to NCF is Ca(2+)-independent, implying that it
      plays a different role in clathrin-mediated endocytosis.

PMID- 22961473
TI  - Schizandrin prevents dexamethasone-induced cognitive deficits.
AB  - OBJECTIVE: To model glucocorticoid-induced cognitive impairment and evaluate the
      neuroprotection by schizandrin (Sch) against dexamethasone (Dex)-induced
      neurotoxicity in vivo and in vitro. METHODS: Cerebral cortical cells from
      neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9
      days, and then treated with Dex (10(-4), 10(-5), 10(-6) or 10(-7) mol/L) for 24 h
      or pretreated with 10(-4) mol/L Dex for 24 h followed by 10, 20, 40, or 80
      MUmol/L Sch for 48 h. Cell viability was assessed using the MTT assay.
      Immunofluorescence and real-time PCR for MAP2 were performed to confirm the
      effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided
      into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I
      (5 mg/kg . d(-1) Dex i.g. treatment for 28 days followed by i.g. vehicle for 14
      days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days
      followed by 5, 15, or 45 mg/kg . d(-1) Sch i.g. for 14 days). Learning and memory
      were assessed by Morris water maze test. Histological examination was used to
      assess pathology and apoptosis in neurons. RESULTS: Compared to the Dex groups,
      Sch increased cell viability in a dose-dependent manner, improved performance in
      the Morris water maze and ameliorated the morphological changes. CONCLUSION: Sch
      has neuroprotective effects against insults induced by glucocorticoid.

PMID- 22961474
TI  - 3-Nitropropionic acid modifies neurotrophin mRNA expression in the mouse
      striatum: 18S-rRNA is a reliable control gene for studies of the striatum.
AB  - OBJECTIVE: The aim of the present study was to determine the changes in the mRNA
      levels of neurotrophins and their receptors in the striatal tissue of mice
      treated with 3-nitropropionic acid (3-NP). METHODS: At 1 and 48 h after the last
      drug administration, the mRNA expression of nerve growth factor, brain-derived
      neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 as well as their
      receptors p75, TrkA, TrkB and TrkC, was evaluated using semi-quantitative (semi
      Q) and real-time RT-PCR. beta-actin mRNA and ribosomal 18S (18S rRNA) were tested
      as internal controls. RESULTS: 3-NP treatment did not affect mRNA expression of
      all neurotrophins and their respective receptors equally. Also, differences in
      neurotrophin and receptor mRNA expression were observed between semi-Q and real
      time RT-PCR. Real-time RT-PCR was more accurate in evaluating the mRNA expression
      of the neurotrophins than semi-Q, and 18S rRNA was more reliable than beta-actin
      as an internal control. CONCLUSION: Neurotrophins and their receptors expression
      is differentially affected by neuronal damage produced by inhibition of
      mitochondrial respiration with 3-NP treatment in low, sub-chronic doses in vivo.

PMID- 22961475
TI  - Altered regional homogeneity in post-traumatic stress disorder: a resting-state
      functional magnetic resonance imaging study.
AB  - OBJECTIVE: Little is known about the brain systems that contribute to
      vulnerability to post-traumatic stress disorder (PTSD). Comparison of the resting
      state patterns of intrinsic functional synchronization, as measured by functional
      magnetic resonance imaging (fMRI), between groups with and without PTSD following
      a traumatic event can help identify the neural mechanisms of the disorder and
      targets for intervention. METHODS: Fifty-four PTSD patients and 72 matched
      traumatized subjects who experienced the 2008 Sichuan earthquake were imaged with
      blood oxygen level-dependent (BOLD) fMRI and analyzed using the measure of
      regional homogeneity (ReHo) during the resting state. RESULTS: PTSD patients
      presented enhanced ReHo in the left inferior parietal lobule and right superior
      frontal gyrus, and reduced ReHo in the right middle temporal gyrus and lingual
      gyrus, relative to traumatized individuals without PTSD. CONCLUSION: Our findings
      showed that abnormal brain activity exists under resting conditions in PTSD
      patients who had been exposed to a major earthquake. Alterations in the local
      functional connectivity of cortical regions are likely to contribute to the
      neural mechanisms underlying PTSD.

PMID- 22961476
TI  - Neuropsychological study of patients with obsessive-compulsive disorder and their
      parents in China: searching for potential endophenotypes.
AB  - OBJECTIVE: The existence of neuropsychological deficits has been implicated in
      obsessive-compulsive disorder (OCD), particularly memory, attention, and
      executive functions. However, few studies have focused on neuropsychological
      deficits in the relatives of OCD patients. The aim of this study was to
      investigate cognitive deficits in OCD patients and their parents. METHODS: Forty
      patients with OCD, 48 parents of these patients, and 87 healthy controls
      completed a neuropsychological testing battery. RESULTS: Both OCD patients and
      their parents showed impairments in delayed verbal memory and delayed visual
      memory. Furthermore, they performed worse than healthy controls in problem
      solving ability. CONCLUSION: Our study demonstrated familial aggregation of
      delayed memory deficits and impaired problem-solving ability, which may be the
      potential neuropsychological endophenotypes of hereditary susceptibility to OCD.

PMID- 22961477
TI  - Dysfunction of two lysosome degradation pathways of alpha-synuclein in
      Parkinson's disease: potential therapeutic targets?
AB  - Parkinson's disease (PD) is pathologically characterized by the presence of alpha
      synuclein (alpha-syn)-positive intracytoplasmic inclusions named Lewy bodies in
      the dopaminergic neurons of the substantia nigra. A series of morbid consequences
      are caused by pathologically high amounts or mutant forms of alpha-syn, such as
      defects of membrane trafficking and lipid metabolism. In this review, we consider
      evidence that both point mutation and overexpression of alpha-syn result in
      aberrant degradation in neurons and microglia, and this is associated with the
      autophagy-lysosome pathway and endosome-lysosome system, leading directly to
      pathological intracellular aggregation, abnormal externalization and re
      internalization cycling (and, in turn, internalization and re-externalization),
      and exocytosis. Based on these pathological changes, an increasing number of
      researchers have focused on these new therapeutic targets, aiming at alleviating
      the pathological accumulation of alpha-syn and re-establishing normal
      degradation.

PMID- 22961478
TI  - Benfotiamine prevents increased beta-amyloid production in HEK cells induced by
      high glucose.
AB  - OBJECTIVE: To determine whether high glucose enhances beta-amyloid (Abeta)
      production in HEK293 Swedish mutant (APPsw) cells with Abeta precursor protein
      (APP) overexpression, and whether under this condition benfotiamine reduces the
      increased Abeta production. METHODS: HEK293 APPsw cells were cultured with
      different concentrations of glucose for different times. The Abeta content in the
      supernatant was determined by ELISA. To investigate the mechanism by which
      benfotiamine reduced Abeta production, glycogen synthase kinase-3 (GSK-3)
      activity and expression were measured after the cells were cultured with 5.5 g/L
      glucose for 12 h. RESULTS: With 1.0, 3.0, 4.5, 5.5, 6.5, 7.5, 8.5, or 10.5 g/L
      glucose, Abeta production by HEK293 APPsw cells was highest in the presence of
      5.5 g/L glucose for 6 and 12 h. The difference in Abeta content between 5.5 and
      1.0 g/L was most marked after incubation for 12 h. Benfotiamine at 20 and 40
      MUg/mL significantly reduced Abeta production in cells incubated with 5.5 g/L
      glucose for 12 h. Moreover, 40 MUg/mL benfotiamine significantly enhanced the
      ratio of phosphorylated GSK-3 to total GSK-3, together with consistent down
      regulation of GSK-3 activity. CONCLUSION: High glucose increases Abeta production
      by HEK293 APPsw cells while benfotiamine prevents this increase. This is
      correlated with the modulation of GSK-3 activity.

PMID- 22961479
TI  - Expression of microRNA machinery proteins in different types of chronic
      rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Dysregulation of microRNAs (miRNAs) has recently been
      shown in chronic rhinosinusitis (CRS), the biogenesis and function of which are
      modulated by miRNA machinery proteins. The expression of these proteins in
      inflammatory airway diseases is unclear. The aim of this study was to investigate
      the expression of miRNA machinery components in CRS. STUDY DESIGN: Case-control
      experimental study. METHODS: The mRNA expression levels of miRNA machinery
      components including Drosha, Dicer, protein activator of the interferon-induced
      protein kinase (PACT), human immunodeficiency virus transactivating response RNA
      binding protein, fragile X mental retardation protein, and argonaute 2/eukaryotic
      translation initiation factor 2C, 2 in nasal biopsies from control, CRS without
      nasal polyps (CRSsNP), eosinophilic, and noneosinophilic CRS with nasal polyps
      (CRSwNP) subjects were determined by quantitative reverse transcription
      polymerase chain reaction. Immunohistochemical staining was employed to examine
      the protein expression of PACT and the cellular source of PACT. RESULTS: Among
      the tested components, only PACT mRNA expression was found to be altered in CRS,
      the levels of which were upregulated in CRSwNP as compared with control. In
      comparison with control and CRSsNP, PACT protein expression was also
      significantly upregulated in CRSwNP, with a further increase in eosinophilic
      CRSwNP. PACT was mainly expressed in CD138(+)  plasma cells. A higher percentage
      of PACT-positive plasma cells in total plasma cells was detected in eosinophilic
      CRSwNP than in noneosinophilic CRSwNP. PACT protein expression correlated with
      disease severity and eosinophil infiltration. CONCLUSIONS: PACT may be associated
      with the plasma cell function and eosinophilic inflammation in CRSwNP. However,
      further experimentation is needed to clarify the functions of PACT.

PMID- 22961481
TI  - Tyrosine kinase inhibitor (TKI)-induced cardiotoxicity: approaches to narrow the
      gaps between preclinical safety evaluation and clinical outcome.
AB  - Although therapies targeted to inhibit the activity of certain tyrosine kinases
      (TK) have helped advance cancer therapy in recent years, reports of cardiac
      toxicity following treatment with tyrosine kinase inhibitors (TKIs) were
      unexpected and not well predicted by preclinical studies. Such clinical findings
      exposed gaps in current preclinical drug testing for predicting the development
      of cardiac toxicities in humans. These gaps included a lack of a comprehensive
      TKI mechanism of action determination and appropriate cardiac functional
      evaluation. New preclinical approaches are suggested to address these issues. In
      addition to tyrosine kinase inhibition, other factors that may play a role in
      drug-induced cardiac effects should be assessed, such as unintended secondary
      targets of TKIs, toxic drug metabolites and drug accumulation in the heart. Both
      on-target and off-target toxic effects of TKIs on cultured cardiac myocytes have
      now been shown to be detectable, providing a rationale for using cardiomyocytes
      as a screening tool to study potential TKI-mediated cardiotoxicity. Incorporating
      isolated perfused heart methodology to chronic/subchronic rodent studies or
      including echocardiography in chronic large animal toxicity studies may improve
      the detection of changes in cardiac function over current methods, and they may
      eventually become a routine tool for screening drugs with suspected cardiotoxic
      potential. Further, assessing drug toxicity and efficacy together in an animal
      model of disease is highly informative for candidate drug selection, and should
      be encouraged to assess specific safety endpoints, such as cardiovascular
      function. Together, these approaches will help better close the gaps between
      preclinical testing and clinical outcomes.

PMID- 22961480
TI  - The role of adenosine receptor agonist and antagonist on Hippocampal MDMA
      detrimental effects; a structural and behavioral study.
AB  - There is abundant evidence showing that repeated use of MDMA (3, 4
      Methylenedioxymethamphetamine, ecstasy) has been associated with depression,
      anxiety and deficits in learning and memory, suggesting detrimental effects on
      hippocampus. Adenosine is an endogenous purine nucleoside that has a
      neuromodulatory role in the central nervous system. In the present study, we
      investigated the role of A2a adenosine receptors agonist (CGS) and antagonist
      (SCH) on the body temperature, learning deficits, and hippocampal cell death
      induced by MDMA administration. In this study, 63 adult, male, Sprague - Dawley
      rats were subjected to MDMA (10 and 20 mg/kg) followed by intraperitoneal CGS
      (0.03 mg/kg) or SCH (0.03 mg/kg) injection. The animals were tested for spatial
      learning in the Morris water maze (MWM) task performance, accompanied by a
      recording of body temperature, electron microscopy and stereological study. Our
      results showed that MDMA treatment increased body temperature significantly, and
      impaired the ability of rats to locate the hidden platform(P < 0.05). The number
      of hippocampal dark neurons also increased especially in CA1. These impairments
      were aggravated by co-administration of A2a antagonist (SCH) with MDMA.
      Furthermore, the administration of the A2a receptor agonist (CGS) provided
      partial protection against MWM deficits and hippocampal cell death(P < 0.05).
      This study provides for the first time evidence that, in contrast to A2a
      antagonist (SCH) effects, co-administration of A2a agonist (CGS) with MDMA can
      protect against MDMA hippocampal neurotoxic effects; providing a potential value
      in the prevention of learning deficits observed in MDMA users. However, the exact
      mechanism of these interactions requires further studies.

PMID- 22961482
TI  - Foxp3 overexpression decreases sensitivity to chemotherapy in mouse Lewis lung
      cancer cells.
AB  - Chemotherapy is the main strategy for the treatment of lung cancer. However,
      sensitivity to chemotherapy, one of the main factors affecting the survival rate
      of patients with lung cancer, is extremely poor. Forkhead box P3 (Foxp3) is the
      key regulatory gene for the development and function of CD4+CD25+ regulatory T
      cells (Tregs). Increased levels of Tregs and Foxp3 expression in the peripheral
      blood and tumour specimens of cancer patients are associated with tumour
      progression and poor prognosis. In addition, certain studies have suggested that
      Tregs may be resistant to conventional chemotherapy and thus, enhance tumour
      immune evasion. Previous studies have demonstrated that Foxp3 is also expressed
      within tumour cells and that it may mimic the function of Tregs. Currently, the
      correlation between the tumour cell expression of Foxp3 and sensitivity to
      chemotherapy is unclear. Therefore, it was hypothesised that Foxp3 causes
      resistance to chemotherapeutic agents in lung cancer cells and that it may
      consequently promote the progression of lung cancer. In the current study, the
      expression of Foxp3 in mouse Lewis lung cancer (LLC) cells was detected using RT
      PCR and immunocytochemistry. The overexpression of Foxp3, which was accomplished
      by the transient transfection of recombinant pcDNA3.1-Foxp3 or empty plasmids
      into LLC cells, was confirmed by RT-PCR and western blot analysis. The inhibition
      of cell proliferation was measured using MTT assay. The expression of multidrug
      resistance protein 1 (mdr1) mRNA and its protein product, P-glycoprotein (P-gp),
      were detected by RT-PCR and flow cytometry, respectively. The results revealed
      that Foxp3 was expressed by LLC cells. The inhibitory rate of cell proliferation
      in Foxp3-overexpressing LLC cells compared with those transfected with an empty
      plasmid was significantly decreased following adriamycin (ADM) and mitomycin C
      (MMC) treatment. The IC50 values of ADM and MMC in Foxp3-overexpressing LLC cells
      were increased. The expression levels of mdr1 mRNA and P-gp were significantly
      upregulated in Foxp3 overexpressing LLC cells. These results suggest that Foxp3
      reduces the sensitivity of LLC cells to ADM and MMC, thus promoting tumour
      progression, by upregulating the expression of mdr1 mRNA and P-gp.

PMID- 22961483
TI  - Fish and seafood availability in markets in the Baie des Chaleurs region, New
      Brunswick, Canada: a heavy metal contamination baseline study.
AB  - The consumption of halieutic products has many health benefits. However, their
      contaminants loads need to be addressed to better understand the risk from
      consuming these products. The aquatic biota from the Baie des Chaleurs in New
      Brunswick is contaminated by cadmium, zinc and lead. In spite of this, no study
      has examined the heavy metal concentrations in commercial halieutic products sold
      in this Canadian region. The objective of this pilot study was to characterize
      the species and origin of fish and seafood sold in the Baie des Chaleurs region
      by using an ecosystemic approach. Additionally, a baseline picture of the heavy
      metal levels found in these products has been determined. In 2008, interviews
      were carried out in markets located in the Baie des Chaleurs area. Species that
      were identified as the most purchased were then bought for analysis. Samples were
      freeze-dried and homogenized before nitric acid digestions. Aluminum, copper,
      cadmium, iron, manganese, and zinc concentrations were determined by inductively
      coupled plasma optical emission spectrometry. Results show that 36 % of seafood
      species sold in markets were caught in the Baie des Chaleurs. Lobsters, shrimps,
      scallops and oysters are the most purchased species regardless of the season.
      High amounts of cadmium exceeding tolerable daily intake are found in lobster
      hepatopancreas and can cause deleterious effects on health, in particular in
      vulnerable populations such as children and heavy consumers. The ecosystemic
      approach to health used in this pilot study shows the feasibility of an
      exhaustive study on the exposure of coastal population to heavy metal from fish
      and seafood consumption and the source of halieutic products sold in markets.

PMID- 22961484
TI  - Preparation and characterization of surfactant-modified hydroxyapatite/zeolite
      composite and its adsorption behavior toward humic acid and copper(II).
AB  - A novel composite material, i.e., surfactant-modified hydroxyapatite/zeolite
      composite, was used as an adsorbent to remove humic acid (HA) and copper(II) from
      aqueous solution. Hydroxyapatite/zeolite composite (HZC) and surfactant-modified
      HZC (SMHZC) were prepared and characterized by X-ray diffraction, Fourier
      transform infrared spectroscopy, and field emission scanning electron microscope.
      The adsorption of HA and copper(II) on SMHZC was investigated. For comparison
      purposes, HA adsorption onto HZC was also investigated. SMHZC exhibited much
      higher HA adsorption capacity than HZC. The HA adsorption capacity for SMHZC
      decreased slightly with increasing pH from 3 to 8 but decreased significantly
      with increasing pH from 8 to 12. The copper(II) adsorption capacity for SMHZC
      increased with increasing pH from 3 to 6.5. The adsorption kinetic data of HA and
      copper(II) on SMHZC obeyed a pseudo-second-order kinetic model. The adsorption of
      HA and copper(II) on SMHZC took place in three different stages: fast external
      surface adsorption, gradual adsorption controlled by both film and intra-particle
      diffusions, and final equilibrium stage. The equilibrium adsorption data of HA on
      SMHZC better fitted to the Langmuir isotherm model than the Freundlich isotherm
      model. The equilibrium adsorption data of copper(II) on SMHZC could be described
      by the Langmuir, Freundlich, and Dubinin-Radushkevich isotherm models. The
      presence of copper(II) in solution enhanced HA adsorption onto SMHZC. The
      presence of HA in solution enhanced copper(II) adsorption onto SMHZC. The
      mechanisms for the adsorption of HA on SMHZC at pH 7 may include electrostatic
      attraction, organic partitioning, hydrogen bonding, and Lewis acid-base
      interaction. The mechanisms for the adsorption of copper(II) on SMHZC at pH 6 may
      include surface complexation, ion exchange, and dissolution-precipitation. The
      obtained results indicate that SMHZC can be used as an effective adsorbent to
      simultaneously remove HA and copper(II) from water.

PMID- 22961485
TI  - Applying waste management scenarios in the Peloponnese Region in Greece: a
      critical analysis in the frame of life cycle assessment.
AB  - The aim of this paper is to apply life cycle assessment in the waste management
      sector, in order to compare the environmental performance of different waste
      management methods. The methods that are studied are: landfilling, aerobic and
      anaerobic biological treatment, incineration and recycling, focusing on mass and
      energy balances and the environmental performance of each applied scenario. The
      Peloponnese Region in Greece was selected as a case for the application of this
      methodology and more specifically its largest municipalities, where a significant
      amount of waste is presented. The conducted LCA study proves the necessity of the
      adoption of an integrated waste management system and indicates its principal
      objectives by measuring environmental impacts. Thermal scenario contributes
      significant to the mitigation on the Greenhouse Gases. On the other hand,
      separation at source and recycling practices provides significant benefits to the
      abiotic depletion impact.

PMID- 22961486
TI  - Artificial radioactivity in environmental media (air, rainwater, soil,
      vegetation) in Austria after the Fukushima nuclear accident.
AB  - Several environmental media in Austria were monitored for artificial
      radionuclides released during the Fukushima nuclear accident. Air (up to 1.2
      mBq/m(3) particulate (131)I) and rainwater (up to 5.2 Bq/L (131)I) proved to be
      the media best suited for the environmental monitoring, allowing also a temporal
      resolution of the activity levels. Significant regional differences in the wet
      deposition of (131)I with rain could be observed within the city of Vienna during
      the arrival of the contaminated air masses. Forward-trajectory analysis supported
      the hypothesis that the contaminated air masses coming from the northwest changed
      direction to northeast over Northern Austria, leading to a strong activity
      concentration gradient over Vienna. In the course of the environmental monitoring
      of the Fukushima releases, this phenomenon-significant differences of (131)I
      activity concentrations in rainwater on a narrow local scale (8.1 km)-appears to
      be unique. Vegetation (grass) was contaminated with (131)I and/or (137)Cs at a
      low level. Soil (up to 22 Bq/kg (137)Cs) was only affected by previous releases
      (nuclear weapon tests, Chernobyl). Here, also significant local differences can
      be observed due to different deposition rates during the Chernobyl accident. The
      effective ecological half-lives of (137)Cs in soil were calculated for four
      locations in Austria. They range from 7 to 30 years. No Austrian sample
      investigated herein exceeded the detection limit for (134)Cs; hence, the
      Fukushima nuclear accident did not contribute significantly to the total
      radiocesium inventory in Austrian environmental media. The levels of detected
      radioactivity were of no concern for public health.

PMID- 22961487
TI  - Mineralogical study and leaching behavior of a stabilized harbor sediment with
      hydraulic binder.
AB  - The environmental assessment of potential effects of contaminated harbor
      sediments stabilized with hydraulic binders and the determination of remediation
      endpoints require the determination of pollutants leaching potentials. Moreover,
      little information about the speciation and mobility of inorganic contaminants in
      these specific solid matrices is available in the literature. The objective of
      this paper is to investigate the relationship between mineralogy and leachability
      of contaminants (copper, lead, and zinc) present in a French harbor sediment
      stabilized with quicklime and Portland cement. Batch equilibrium leaching tests
      at various pH, chemical analysis of leachates, and mineralogical studies (X-ray
      diffraction, scanning electron microscopy-energy dispersive spectroscopy, and
      diffuse reflectance infrared Fourier transform) have been combined in the present
      investigation. The acid neutralization capacity of the stabilized matrix studied
      is first controlled by the dissolution of portlandite (pH ~12), followed by the
      dissolution of C-S-H (pH ~11) and the dissolution of ettringite (pH ~10).
      Finally, a very high buffering capacity of this stabilized sediment is observed
      for pH values around 6. This equilibrium is mainly controlled by the dissolution
      of iron sulfides and carbonate minerals. Consequently, the mobilization of
      inorganic contaminants as a function of pH remains very low (<0.1 wt%) for pH
      values above 6 and significantly increases for pH below these values. This
      research confirms the importance of a combined methodology for the intrinsic
      characterization of potential mobilization of contaminants in a stabilized
      sediment and for a better understanding of geochemical processes that affect
      contaminant fate, transformation, and transport in the subsurface environment.

PMID- 22961488
TI  - Biosorption characteristics of Bacillus gibsonii S-2 waste biomass for removal of
      lead (II) from aqueous solution.
AB  - Lead (II) has been as one of the most toxic heavy metals because it is associated
      with many health hazards. Therefore, people are increasingly interested in
      discovering new methods for effectively and economically scavenging lead (II)
      from the aquatic system. Recent studies demonstrate biosorption is a promising
      technology for the treatment of pollutant streams. To apply these techniques,
      suitable adsorbents with high efficiency and low cost are demanded. The waste
      biomass of Bacillus gibsonii S-2 biosorbent was used as low-cost biosorbent to
      remove metallic cations lead (II) from aqueous solution. To optimize the maximum
      removal efficiency, the effect of pH and temperature on the adsorption process
      was studied. The isotherm models, kinetic models and thermodynamic parameters
      were analysed to describe the adsorptive behaviour of B. gibsonii S-2 biosorbent.
      The mechanisms of lead (II) biosorption were also analysed by FTIR and EDX. The
      results showed that the optimum pH values for the biosorption at three different
      temperatures, i.e. 20, 30 and 40  degrees C, were determined as 4. The
      equilibrium data were well fitted to Langmuir model, with the maximum lead (II)
      uptake capacities of 333.3 mg g(-1). The kinetics for lead (II) biosorption
      followed the pseudo-second-order kinetic equation. The thermodynamic data showed
      that the biosorption process were endothermic (?G <0), spontaneous (?H>0) and
      irreversible (?S>0). The mechanism of lead (II) biosorption by the waste biomass
      of B. gibsonii S-2 biosorbent could be a combination of ion exchange and
      complexation with the functional groups present on the biosorbent surface. The
      application of the waste biomass of B. gibsonii S-2 for lead (II) adsorption,
      characterized with higher lead (II) sorption capacity and lower cost, may find
      potential application in industrial wastewater treatment.

PMID- 22961489
TI  - Semi-specific Microbacterium phyllosphaerae-based microbial sensor for
      biochemical oxygen demand measurements in dairy wastewater.
AB  - Although the long incubation time of biochemical oxygen demand (BOD7)
      measurements has been addressed by the use of microbial biosensors, the resulting
      sensor-BOD values gained from the measurements with specific industrial
      wastewaters still underestimates the BOD value of such samples. This research
      aims to provide fast and more accurate BOD measurements in the dairy wastewater
      samples. Unlike municipal wastewater, wastewater from the dairy industry contains
      many substrates that are not easily accessible to a majority of microorganisms.
      Therefore, a bacterial culture, Microbacterium phyllosphaerae, isolated from
      dairy wastewater was used to construct a semi-specific microbial biosensor. A
      universal microbial biosensor based on Pseudomonas fluorescens, which has a wide
      substrate spectrum but is nonspecific to dairy wastewater, was used as a
      comparison. BOD biosensors were calibrated with OECD synthetic wastewater, and
      experiments with different synthetic and actual wastewater samples were carried
      out. Results show that the semi-specific M. phyllosphaerae-based microbial
      biosensor is more sensitive towards wastewaters that contain milk derivates and
      butter whey than the P. fluorescens-based biosensor. Although the M.
      phyllosphaerae biosensor underestimates the BOD7 value of actual dairy
      wastewaters by 25-32%, this bacterial culture is more suitable for BOD monitoring
      in dairy wastewater than P. fluorescens, which underestimated the same samples by
      46-61%.

PMID- 22961490
TI  - Pesticide pressure and fish farming in barrage pond in Northeastern France. Part
      II: residues of 13 pesticides in water, sediments, edible fish and their
      relationships.
AB  - Residues of pesticides in fish farming productions from barrage ponds are seldom
      studied in spite of increasing health questionings and environmental concerns.
      The purpose of this study is to establish the pesticide contamination profiles of
      sediments and edible fish from five ponds in Northeastern France. Multi-residues
      method and liquid chromatography-tandem mass spectrometry analysis were used to
      quantify 13 pesticides (azoxystrobin, carbendazim, clomazone, diflufenican,
      dimethachlor, fluroxypyr, iprodion, isoproturon, mesosulfuron-methyl,
      metazachlor, napropamid, quizalofop and thifensulfuron-methyl). Ten sediments and
      143 muscles samples were analysed, corresponding to two successive fishing
      campaigns (first fishing date and second fishing date (P2), about 1 year later)
      on five sites (noted C-0, C-25, C-45, C-75 and C-85 to express the increasing
      gradient of crop area). Isoproturon was present in all sediments samples (1.8
      56.4 MUg/kg dry weight). During P2 period, carbendazim was quantified in the fish
      of site C-0 (0.09 +/- 0.02, 0.2 +/- 0.1 and 0.17 +/- 0.06 MUg/kg wet weight (ww)
      for roach, carp and perch, respectively). Metazachlor was only quantified in
      perch of the site C-25 (0.13 +/- 0.02 MUg/kg ww). Concentrations of isoproturon
      were similar for the sites C-45 and C-75 with 0.4 +/- 0.1 and 0.75 +/- 0.06
      MUg/kg ww for carp and perch, respectively. Contamination of fish reflected
      generally concentrations in surroundings. Isoproturon was the most concentrated
      and its main source was water for perch while carp was exposed through both water
      and sediments, highlighting their life strategies in pond.

PMID- 22961492
TI  - [To remain human while aging... :  What are the elderly really of value to us?].

PMID- 22961491
TI  - Nitrogen impacts on atrazine-degrading Arthrobacter strain and bacterial
      community structure in soil microcosms.
AB  - The objective of this study was to investigate the impacts of exogenous nitrogen
      on a microbial community inoculated with the atrazine-degrading Arthrobacter sp.
      in soil amended with a high concentration of atrazine. Inoculated and
      uninoculated microcosms for biodegradation tests were constructed. Atrazine
      degradation capacity of the strain DAT1 and the strain's atrazine-metabolic
      potential and survival were assessed. The relative abundance of the strain DAT1
      and the bacterial community structure in soils were characterized using
      quantitative PCR in combination with terminal restriction fragment length
      polymorphism. Atrazine degradation by the strain DAT1 and the strain's atrazine
      metabolic potential and survival were not affected by addition of a medium level
      of nitrate, but these processes were inhibited by addition of a high level of
      nitrate. Microbial community structure changed in both inoculated and
      uninoculated microcosms, dependent on the level of added nitrate. Bioaugmentation
      with the strain DAT1 could be a very efficient biotechnology for bioremediation
      of soils with high concentrations of atrazine.

PMID- 22961493
TI  - [Ageing and change of values].
AB  - The process of ageing and the relevant scientific disciplines are influenced by
      societal values und priorities. Values are the object of scientific and public
      reflection mainly in times of strong changes and obvious conflicts. The article
      discusses fundamental social and cultural changes from collective integration to
      personal freedom and autonomy. The focus of this paper is directed towards the
      impact of the consequences and contradictions of such cultural changes on the
      process of ageing and of ageing research.

PMID- 22961494
TI  - Transcriptome alterations induced by cigarette smoke.
AB  - Cigarette smoke alters the transcriptome of multiple tissues; those directly
      exposed to toxic products and those exposed to circulating components and
      metabolic products of tobacco smoke. In most tissues and organs that have been
      studied, the smoking transcriptome is characterized by increased expression of
      antioxidant and xenobiotic genes as well as a wide spectrum of inflammation
      related genes, and potential oncogenic genes. Smoking is associated with an
      increased incidence of cancer in a number of organs both those directly exposed
      (lungs and airways) and those indirectly exposed (bladder, liver, pancreas).
      Individual transcriptomic responses vary, based to some degree on as yet to be
      clarified genetic factors, and likely how and what the individual has smoked. The
      complexity of individual responses to tobacco exposure and of smoking-related
      cancers in various organs is beginning to be revealed in transcriptomic and whole
      genome sequencing studies, of both tumors and cytologically normal appearing
      cells that have been exposed to cigarette smoke or its products creating a
      genomic "field of injury." The recent application of next generation sequencing
      to defining the transcriptome alterations induced by cigarette smoke holds the
      promise of discovering new approaches to personalized prevention and treatment of
      smoking-related lung diseases in the future.

PMID- 22961495
TI  - Analyzing left ventricular function in mice with Doppler echocardiography.
AB  - Mice are widely used in heart failure research. Accurate evaluation of cardiac
      structure and function is key to modern cardiovascular research. Doppler
      echocardiography is a simple, reproducible, and non-invasive method, which allows
      a longitudinal study of these small animals. Besides common parameters such as
      left ventricular chamber size, mass, and function, new emerging echo tools are of
      great interest for small animal imaging. In this review, we describe the
      technical issues linked to murine cardiovascular anatomy and physiology and the
      most current echo parameters that can be used.

PMID- 22961496
TI  - Success rates, quality of life, and feasibility of sacral nerve stimulation in
      elderly patients: 1-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: Urgency urinary incontinence (UUI) frequently occurs
      in elderly. International guidelines recommend pharmacological therapy as first
      line treatment, but elderly do not respond in many cases. The purpose of this
      study was to report cure rates, quality of life, and feasibility of sacral
      neurostimulation (SNS) as an alternative option in the elderly. MATERIALS AND
      METHODS: From October 2008 to April 2010, women >65 years with UUI who were
      refractory to pharmacological treatments were enrolled in this study and
      underwent SNS. At 12 months after surgery, patients were asked to compile a 3-day
      voiding diary and a urogynecologic standardized questionnaire: the Overactive
      Bladder Questionnaire (OAB-q). RESULTS: Eighteen patients met our inclusion
      criteria. Fifteen (83.3 %) underwent implantation of the neuromodulator. Twelve
      months after surgery, an overall success rate of 83.3 % was registered. A
      statistically significant difference (P<0.0001) between baseline and postsurgery
      OAB-q scores was recorded. CONCLUSIONS: SNS can be considered an alternative
      treatment for UUI in older women.

PMID- 22961497
TI  - Electrophysiological evaluation of the pudendal nerve and urethral innervation in
      female stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Although still a matter of debate, stress urinary
      incontinence (SUI) may be accompanied by damage to urethral and pelvic floor
      innervations, thus promoting dysfunctions of the urethral support and sphincteric
      closure mechanisms. The aim of this study was to analyze the pelvic floor and
      urethral innervations through pelvic electrophysiological tests to identify
      whether neurological alterations interfere with urinary continence and urethral
      functional activity. METHODS: This prospective study included 52 women, 33 with
      clinically and urodynamically proven SUI and 19 continent volunteers matched for
      age, height, parity, and number of vaginal deliveries by the propensity score
      method. The patients were divided according to the severity of urinary loss
      evaluated by measuring abdominal leak point pressure (ALPP). Pudendal nerve
      terminal motor latency (PNTML), pudendal somatosensory evoked potential (SSEP)
      latencies, urethral and clitoral sensory thresholds, and urethroanal reflex
      latency were tested. RESULTS: SUI and control subjects did not differ in PNTML,
      SSEP latency, and clitoral sensory thresholds. However, reduced responsiveness to
      urethral electrosensitivity and prolonged urethroanal reflex latency were
      detected in most incontinent patients. In addition, urethral electrosensitivity
      was altered in suspected intrinsic sphincteric dysfunction. CONCLUSIONS: Urethral
      afferent pathways can be altered in women with SUI and may play an important role
      in evoking intrinsic sphincteric dysfunction.

PMID- 22961498
TI  - Attitudes toward couples-based HIV counseling and testing among MSM in Cape Town,
      South Africa.
AB  - Couples-based voluntary HIV counseling and testing (CVCT) allows couples to
      receive their HIV test results together and has been demonstrated to be effective
      in reducing HIV transmission, increasing and sustaining condom use, and reducing
      sexual risk-taking among at-risk heterosexual couples. However, the acceptability
      of CVCT among MSM has yet to be evaluated in an African setting. The results from
      seven focus group discussions and 29 in-depth interviews conducted in Cape Town,
      South Africa exhibit overwhelmingly high acceptance of CVCT. Participants were
      attracted to the counseling components of the service, stating that these would
      allow for the couple to increase their commitment and to explore methods of how
      to effectively reduce their risk of acquiring or transmitting HIV in the presence
      of a trained counselor. These results suggest CVCT would be highly welcomed and
      could work to fill the significant lack of services available and accessible to
      MSM couples in Cape Town.

PMID- 22961499
TI  - Development and validation of a brief computer-administered HIV-Related Health
      Literacy Scale (HIV-HL).
AB  - Health literacy is related to a number of health status variables and has been
      associated with medication adherence in persons treated for HIV infection.
      Currently-available measures of health literacy require lengthy administration or
      have content or format limitations. In this paper we report the preliminary
      development and validation of a brief computer-administered health literacy test
      that includes content focused on medication adherence as well as questions based
      on a video simulation of an HIV-related clinical encounter. The measure shows
      significant relations with other measures of health literacy, HIV-related
      knowledge, and electronically-measured medication adherence. We also present
      receiver operating characteristic analyses that provide estimates of various
      scores' sensitivities and specificities so that the HIV-Related Health Literacy
      Scale can be used as a screening measure.

PMID- 22961500
TI  - Effectiveness of respondent driven sampling to recruit undocumented Central
      American immigrant women in Houston, Texas for an HIV behavioral survey.
AB  - Respondent driven sampling (RDS) is widely used for HIV behavioral research among
      sex workers, drug users, and other hidden populations, but has had limited
      application in immigrant populations in the U.S. In 2010, we used RDS to recruit
      undocumented Central American immigrant women in Houston, Texas for an HIV
      behavioral survey. Beginning with three initial participants we recruited 226
      women within 16 weeks. Social networks were dense and participants adopted the
      recruitment system with reasonable ease. Homophily scores indicated moderate
      within-group preference by country of origin. However, cross-group recruitment
      was sufficient to achieve a diverse sample that attained equilibrium for all
      demographic and sexual behavior characteristics. Overall, RDS was easy to
      implement, attained a large sample in a relatively short period of time, and
      reached an otherwise hidden population. Our results suggest that RDS is an
      effective method for recruiting undocumented Latina immigrants for HIV behavioral
      surveys.

PMID- 22961501
TI  - Biological characterizations of [Gd@C82(OH)22]n nanoparticles as fullerene
      derivatives for cancer therapy.
AB  - Malignant tumor disease is one of the leading causes of human death in many
      countries. Currently, chemotherapy is considered highly efficient for cancer
      treatment. However, the clinical application of conventional chemotherapeutic
      agents is limited because of their high toxicity. With the development of
      nanotechnology, engineered nanomaterials have been widely and increasingly used
      in biomedical fields such as biomedicine. Thus, the use of engineered
      nanomaterials has become a promising approach to cancer treatment. Many newly
      fabricated nanomaterials with unique characteristics exhibit favorable
      therapeutic and diagnostic properties, implying their enormous potential as
      biomedical candidates. [Gd@C(82)(OH)(22)](n) is a new type of metallofullerenol
      nanoparticle with high anti-tumor activity but low toxicity. In this article, the
      properties and biological effects of [Gd@C(82)(OH)(22)](n) are summarized, and
      their possible mechanisms are analyzed.

PMID- 22961502
TI  - Inhalation and external doses in coastal villages of high background radiation
      area in Kollam, India.
AB  - The observational evidence for radiation-induced health effects in humans comes
      largely from the exposures to high doses received over short periods of time. The
      rate of induction of any health risk at low doses and dose rates is estimated by
      extrapolation from observations at high doses. Effects of low dose/low dose rate
      could be done by the study of populations that have been exposed to slightly
      above-average natural radiation doses. Southwest coastal line of the Kerala state
      in India is one such region known to have elevated levels of background
      radioactivity mainly due to the mineral-rich sand available with high abundance
      of thorium. In the present work, a study was conducted to investigate the
      inhalation and external radiation doses to human beings in the high background
      radiation area along the southwest coast of Kerala. Five hundred dwellings were
      selected for the study. All the selected houses were at least 10 y old with
      similar construction. Long-term integrated indoor measurements of the external
      gamma dose using thermoluminescent dosemeters (TLDs) and the inhalation dose with
      the SSNTD-based twin-cup dosemeters were carried out in the dwellings
      simultaneously. Ambient gamma dose measurements were also made with a GM tube
      based survey meter while deploying and retrieving the dosemeters. The data show a
      high degree of heterogeneity. The inhalation dose was found to vary from 0.1 to
      3.53 mSv y(-1) and the external dose rates had a range of 383-11419 uGy y(-1).
      The external doses measured by the survey meter and TLDs showed an excellent
      correlation.

PMID- 22961503
TI  - Getting to best care at lower cost.

PMID- 22961504
TI  - Computed tomography features of acinar cell carcinoma of the pancreas.

PMID- 22961505
TI  - Photodermatoses: environmentally induced conditions with high psychological
      impact.
AB  - Photodermatoses are a group of skin disorders caused or exacerbated by
      ultraviolet and/or visible radiation, which collectively affect a high proportion
      of the population and substantially affect quality of life (QoL). Our objective
      was to assess the psychological impact of these conditions. Patients with a range
      of photodermatoses diagnosed at a specialist investigation centre in the UK
      completed questionnaires evaluating (i) anxiety and (ii) depression, using the
      Hospital Anxiety and Depression Scale (HADS), (iii) social anxiety, using the
      Fear of Negative Evaluation measure (FNE), (iv) coping strategies (brief COPE)
      and (v) QoL, using the Dermatology Life Quality Index (DLQI). Questionnaires were
      returned by 185 of 260 patients (71.1% response rate). Mean age was 50.2 years
      (SD 14.5, range 20-85), 80.3% female. Polymorphic light eruption was the most
      common diagnosis, followed by photoaggravated eczema, other photoaggravated
      dermatological conditions and solar urticaria. Across the sample, high
      percentages, i.e. 23% and 7.9% of individuals, showed scores indicating clinical
      levels of anxiety and depression, respectively. Facial involvement was a strong
      indicator for depression (t = 2.7, p < 0.01). In regression analyses
      psychological factors (particularly depression and adaptive coping) were the
      principle predictors of QoL, accounting for 17.7% of the variance (F = 7.61, p <
      0.01), while clinical variables accounted for an additional 10.1% (F = 8.96, p <
      0.01), with number of months/year affected exerting a significant effect (p <
      0.01). This study demonstrates the high psychological comorbidity of these
      conditions; more awareness of this is required, with adoption of a
      biopsychosocial approach to their management.

PMID- 22961506
TI  - Cadophora malorum Cs-8-1 as a new fungal strain producing gibberellins isolated
      from Calystegia soldanella.
AB  - Fourteen endophytic fungi with different colony morphologies were isolated from
      the roots of Calystegia soldanella. Endophytic fungi isolated from C. soldanella
      were identified by internal transcribed spacer (ITS) region. To verify plant
      growth promotion (PGP), culture filtrates of isolated endophytic fungi were
      treated in Waito-c rice (WR) and C. soldanella seedlings. Culture filtrates of Cs
      8-1 fungal strain had advanced PGP activity. The presence of physiologically
      bioactive gibberellins (GA) GA(1) (1.213 ng ml(-1)), GA(3) (1.292 ng ml(-1)),
      GA(4) (3.6 ng ml(-1)), GA(7) (1.328 ng ml(-1)), other inactive GA(9) (0.796 ng
      ml(-1)) and GA(12) (0.417 ng ml(-1)), GA(20) (0.302 ng ml(-1)), GA(24) (1.351 ng
      ml(-1)), GA(34) (0.076 ng ml(-1)), and GA(53) (0.051 ng ml(-1)) in culture
      filtrates of Cs-8-1 fungal strain was detected. The Cs-8-1 fungal strain was
      confirmed as a producer of GAs. Molecular analysis of sequences showed high
      similarity of 99% to Cadophora malorum. Consequentially, the Cs-8-1 fungal strain
      was identified as a new C. malorum producing GAs.

PMID- 22961507
TI  - Laparoscopic ventral hernia repair.

PMID- 22961508
TI  - Request for determination regarding papers published by Dr Yoshitaka Fujii.

PMID- 22961509
TI  - Systematic review of serious games for medical education and surgical skills
      training.
AB  - BACKGROUND: The application of digital games for training medical professionals
      is on the rise. So-called 'serious' games form training tools that provide a
      challenging simulated environment, ideal for future surgical training.
      Ultimately, serious games are directed at reducing medical error and subsequent
      healthcare costs. The aim was to review current serious games for training
      medical professionals and to evaluate the validity testing of such games.
      METHODS: PubMed, Embase, the Cochrane Database of Systematic Reviews, PsychInfo
      and CINAHL were searched using predefined inclusion criteria for available
      studies up to April 2012. The primary endpoint was validation according to
      current criteria. RESULTS: A total of 25 articles were identified, describing a
      total of 30 serious games. The games were divided into two categories: those
      developed for specific educational purposes (17) and commercial games also useful
      for developing skills relevant to medical personnel (13). Pooling of data was not
      performed owing to the heterogeneity of study designs and serious games. Six
      serious games were identified that had a process of validation. Of these six,
      three games were developed for team training in critical care and triage, and
      three were commercially available games applied to train laparoscopic psychomotor
      skills. None of the serious games had completed a full validation process for the
      purpose of use. CONCLUSION: Blended and interactive learning by means of serious
      games may be applied to train both technical and non-technical skills relevant to
      the surgical field. Games developed or used for this purpose need validation
      before integration into surgical teaching curricula.

PMID- 22961510
TI  - Acute aortic dissection type A.
AB  - BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular
      emergency. Clinical presentation ranges from pain related to the acute event,
      collapse due to aortic rupture or pericardial tamponade, or manifestations of
      organ or limb ischaemia. The purpose of this review was to clarify important
      clinical issues of AADA management, with a focus on diagnostic and therapeutic
      challenges. METHODS: Based on a MEDLINE search the latest literature on this
      topic was reviewed. Results from the German Registry for Acute Aortic Dissection
      Type A (GERAADA) are also described. RESULTS: Currently, the perioperative
      mortality rate of AADA is below 20 per cent, the rate of definitive postoperative
      neurological impairment approaches 12 per cent and the long-term prognosis after
      surviving the acute phase of the disease is good. Many pathology- and therapy
      associated factors influence the outcome of AADA, including prompt diagnosis with
      computed tomography and better cerebral protection strategies during aortic arch
      reconstruction. Endovascular technologies are emerging that may lead to less
      invasive treatment options. CONCLUSION: AADA is an emergency that can present
      with a wide variety of clinical scenarios. Advances in the surgical management of
      this complex disease are improving outcomes.

PMID- 22961511
TI  - Systematic review of intravenous methylene blue in parathyroid surgery.
AB  - BACKGROUND: Methylene blue is an intraoperative adjunct for localization of
      enlarged parathyroid glands. The availability of preoperative and other
      intraoperative localization methods, and the reported adverse effects of
      methylene blue make its routine use debatable. The aim of this study was to
      perform a systematic review of the use of methylene blue in parathyroidectomy.
      METHODS: A systematic review of English-language literature in MEDLINE and Scopus
      databases on the use of intravenous methylene blue in parathyroid surgery was
      carried out. RESULTS: There were no randomized clinical trials. Thirty-nine
      observational studies were identified, of which 33 did not have a control arm.
      The overall median staining rate for abnormal parathyroid glands was 100 per
      cent. The median cure rates in the methylene blue and no-methylene blue arms were
      100 and 98 per cent respectively. Neurotoxicity was reported in 25 patients, all
      of whom were taking serotonergic medication. CONCLUSION: Observational evidence
      suggests that methylene blue is efficacious in identifying enlarged parathyroid
      glands. Toxicity appears to be mild in the absence of concomitant use of
      serotonin reuptake inhibitors. The effectiveness of methylene blue in the context
      of currently used preoperative and intraoperative localization techniques has yet
      to be shown.

PMID- 22961512
TI  - Systematic review of intravenous methylene blue in parathyroid surgery (Br J Surg
      2012; 99: 1345-1352).

PMID- 22961513
TI  - Systematic review of single-incision laparoscopic colonic surgery.
AB  - BACKGROUND: Randomized clinical trials (RCTs) have shown multiport laparoscopic
      surgery to be safe compared with open surgery in elective colonic disease. Single
      incision laparoscopic surgery (SILS) represents the latest advance in
      laparoscopic surgery. The aim of this systematic review was to establish the
      safety and complication profile of colonic SILS. METHODS: The search was
      performed in October 2011 using PubMed, MEDLINE, Embase and the Cochrane Central
      Register of Controlled Trials. Search terms were 'colorectal', 'colon',
      'colectomy', 'rectal' and single incision/port/trocar/site/scar. Only pure single
      incision laparoscopic colonic surgery for benign and malignant colonic disease
      was included. Primary outcomes were the early postoperative complication profiles
      of colonic SILS. Secondary outcomes were duration of operation, lymph node
      yields, conversion rate and duration of hospital stay. RESULTS: Colonic SILS data
      were compared with data from a Cochrane review on the short-term outcomes of
      laparoscopic colonic surgery and four main RCTs on laparoscopic colonic surgery.
      Median operating times and time to first bowel motion for colonic SILS were
      comparable with those for laparoscopic colonic surgery. The median lymph node
      retrieval for malignant disease achieved with SILS was acceptable. Evidence for a
      reduction in postoperative pain with SILS was conflicting. There was no
      significant reduction in length of hospital stay with SILS. Most patients
      selected for colonic SILS had a low body mass index, non-bulky tumours and were
      operated on by experienced laparoscopic surgeons. There was significant
      heterogeneity in study group characteristics, indications for surgery, research
      methodology, operative techniques and follow-up time. CONCLUSION: Colonic SILS
      should be restricted to highly selected patients; operations should be performed
      by experienced laparoscopic surgeons, with critical appraisal of clinical
      outcomes.

PMID- 22961514
TI  - Randomized clinical trial of chronic pain after the transinguinal preperitoneal
      technique compared with Lichtenstein's method for inguinal hernia repair.
AB  - BACKGROUND: Preliminary experience has suggested that preperitoneal mesh
      positioning causes less chronic pain than Lichtenstein's technique for inguinal
      hernia repair. Therefore, a randomized clinical trial was conducted with the aim
      of evaluating the incidence of postoperative chronic pain after transinguinal
      preperitoneal (TIPP) mesh repair versus Lichtenstein's technique. METHODS:
      Patients with a primary unilateral inguinal hernia were randomized to either TIPP
      or Lichtenstein's repair in two training hospitals. The primary outcome was the
      number of patients with chronic pain after surgery. Secondary outcomes were
      adverse events. Follow-up was scheduled after 14 days, 3 months and 1 year.
      Patients and outcome assessors were blinded. RESULTS: A total of 302 patients
      were randomized to TIPP (143) or Lichtenstein (159) repair. Baseline
      characteristics were comparable in the two groups. Some 98.0 per cent of the
      patients were included in the analysis (141 in the TIPP group and 155 in the
      Lichtenstein group). Significantly fewer patients in the TIPP group had
      continuous chronic pain 1 year after surgery: five patients (3.5 per cent) versus
      20 patients (12.9 per cent) in the Lichtenstein group (P = 0.004). An additional
      12 patients (8.5 per cent) in the TIPP group and 60 (38.7 per cent) in the
      Lichtenstein group experienced pain during activity (P = 0.001). There were two
      patients with recurrence in the TIPP group and four in the Lichtenstein group,
      but no significant differences were found in other severe adverse events between
      the groups. CONCLUSION: Fewer patients had continuous chronic pain at 1 year
      after the TIPP mesh inguinal hernia repair compared with Lichtenstein's repair.

PMID- 22961515
TI  - Randomized clinical trial on chronic pain after the transinguinal preperitoneal
      technique compared with Lichtenstein's method for inguinal hernia repair (Br J
      Surg 2012; 99: 1365-1373).

PMID- 22961516
TI  - Randomized clinical trial of dexamethasone versus placebo in laparoscopic
      inguinal hernia repair.
AB  - BACKGROUND: The effect of dexamethasone on recovery and length of convalescence
      has not been evaluated in patients after laparoscopic groin hernia repair. It was
      hypothesized that preoperative intravenous dexamethasone would reduce
      postoperative pain. METHODS: Men undergoing transabdominal preperitoneal (TAPP)
      inguinal hernia repair were randomized to receive either a single intravenous
      dose of 8 mg dexamethasone or placebo (saline) 30-60 min before operation in a
      randomized double-blind trial. Patients in the two groups received similar
      standardized anaesthesia and analgesic regimens. The primary outcome measure was
      pain during coughing on postoperative day 1. Secondary outcomes were
      postoperative discomfort, fatigue and length of convalescence. Pain scores,
      discomfort and fatigue were recorded before surgery and daily on postoperative
      days 0-3 in a standard manner using visual analogue, verbal rating and numerical
      rating scales. The use of analgesics and antiemetics on the day of operation was
      recorded. The duration of time away from work and leisure activities was
      registered. RESULTS: The study enrolled 80 patients. No significant differences
      were found between the groups regarding postoperative pain, need for analgesia,
      discomfort, fatigue, nausea, vomiting or length of convalescence. Patients who
      received placebo used significantly more antiemetics in the postanaesthesia care
      unit (PACU) than patients in the dexamethasone group (P = 0.026). CONCLUSION: A
      single preoperative dose of 8 mg dexamethasone before laparoscopic groin hernia
      repair had no clinical effect on early postoperative pain, discomfort or fatigue
      after TAPP inguinal hernia repair, but resulted in a significantly lower use of
      antiemetics in the PACU.

PMID- 22961517
TI  - Randomized clinical trial on the effect of fibrin sealant on latissimus dorsi
      donor-site seroma formation after breast reconstruction.
AB  - BACKGROUND: Latissimus dorsi (LD) flap procedures comprise 50 per cent of breast
      reconstructions in the UK. They are frequently complicated by seroma formation.
      Fibrin sealants may reduce seroma volumes at the donor site. The aim was to
      investigate the effect of fibrin sealant (Tisseel((r))) on total seroma volumes
      from the breast, axilla and back (donor site) after LD breast reconstruction.
      Secondary outcomes were specific back seroma volumes together with incidence and
      severity of wound complications. METHODS: Consecutive women undergoing implant
      assisted or extended autologous LD flap reconstruction were randomized to either
      standard care or application of fibrin sealant to the donor-site chest wall. All
      participants were blinded for the study duration but assessors were only
      partially blinded. Non-parametric methods were used for analysis. RESULTS: A
      total of 107 women were included (sealant 54, control 53). Overall back seroma
      volumes were high, with no significant differences between control and sealant
      groups over 3 months. Fibrin sealant failed to reduce in situ back drainage
      volumes in the 10 days after surgery, and did not affect the rate or volume of
      seromas following drain removal. CONCLUSION: This randomized study, which was
      powered for size effect, failed to show any benefit from fibrin sealant in
      minimizing back seromas after LD procedures.

PMID- 22961518
TI  - Oncoplastic surgery for breast cancer based on tumour location and a quadrant-per
      quadrant atlas.
AB  - BACKGROUND: The majority of published techniques for oncoplastic surgery rely on
      an inverted-T mammoplasty, independent of tumour location. These techniques,
      although useful, cannot be adapted to all situations. A quadrant-per-quadrant
      atlas of mammoplasty techniques for large breast cancers was developed in order
      to offer breast surgeons a technique dependent on tumour location, which reduces
      the risk of postoperative complications and delay to adjuvant therapy. METHODS:
      From 2005 to 2010, a series of eligible women with breast cancer were treated by
      quadrant-specific oncoplastic techniques. All complications and any delay to
      adjuvant treatment were recorded prospectively, along with local and distant
      cancer recurrences. Cosmetic outcome was evaluated using a five-point scale.
      RESULTS: A total of 175 patients were analysed. The median tumour size, after
      histological examination, was 25 (range 4-90) mm. Twenty-three patients (13.1 per
      cent) had involved margins. Seventeen of these patients were treated by
      mastectomy and three had a re-excision. Complications occurred in 13 patients
      (7.4 per cent), which led to a delay to adjuvant treatment in three (1.7 per
      cent). After a median follow-up of 49 (range 23-96) months, three patients had
      developed a local recurrence. The mean score after cosmetic evaluation was 4.6 of
      5. CONCLUSION: A quadrant-per-quadrant approach to oncoplastic techniques for
      breast cancer was developed that tailors the mammoplasty for each tumour
      location. This panel of techniques should be a useful guide for breast surgeons,
      and extends the possibilities for breast conservation for large or poorly limited
      cancers, with a low complication rate and good cosmetic results.

PMID- 22961519
TI  - Prognosis in patients with sentinel node-positive melanoma without immediate
      completion lymph node dissection.
AB  - BACKGROUND: The therapeutic value of immediate completion lymph node dissection
      (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study
      was to evaluate the impact of immediate CLND on the outcome of patients with SN
      positive melanoma. METHODS: Patients with SN metastases treated between 1993 and
      2008 at ten cancer centres from the European Organization for Research and
      Treatment of Cancer Melanoma Group were included in this retrospective study.
      Maximum tumour size, intranodal location and penetrative depth of SN metastases
      were measured. Outcome in those who had CLND was compared with that in patients
      who did not undergo completion lymphadenectomy. RESULTS: Of 1174 patients with SN
      positive melanoma, 1113 (94.8 per cent) underwent CLND and 61 (5.2 per cent) did
      not. Median follow-up for the two groups was 34 and 48 months respectively. In
      univariable survival analysis, CLND did not significantly influence disease
      specific survival (hazard ratio (HR) 0.89, 95 per cent confidence interval 0.58
      to 1.37; P = 0.600). However, patients who did not undergo CLND had more
      favourable prognostic factors. Matched-pair analysis, with matching for age,
      Breslow thickness, tumour ulceration and SN tumour burden, showed that CLND had
      no influence on survival (HR 0.86, 0.46 to 1.61; P = 0.640). After adjusting for
      prognostic factors in multivariable survival analyses, no difference in survival
      was found. CONCLUSION: In these two cohorts of patients with SN-positive melanoma
      and prognostic heterogeneity, outcome was not influenced by CLND.

PMID- 22961520
TI  - Staging and outcome depending on surgical treatment in adenocarcinomas of the
      oesophagogastric junction.
AB  - BACKGROUND: Owing to controversial staging and classification of adenocarcinoma
      of the oesophago-gastric junction (AOG) before surgery, the choice of appropriate
      surgical approach remains problematic. In a retrospective study, preoperative
      staging of AOG and the impact of preoperative misclassification on outcome were
      analysed. METHODS: Data from patients with AOG were analysed from a prospectively
      collected database with regard to surgical treatment, preoperative and
      postoperative staging, and outcome. RESULTS: One-hundred and thirty patients with
      Siewert types I and II AOG who did not have neoadjuvant treatment were included
      in the study: 41 patients with an AOG type I who underwent oesophagectomy, 51
      patients with an AOG staged before surgery as type I who underwent oesophagectomy
      but in whom the final histology showed a type II tumour, and 38 patients whose
      tumours were staged as AOG type II before and after operation who underwent
      gastrectomy. Among patients who had an oesophagectomy, lymph node metastases (P =
      0.022), tumour relapse (P = 0.009) and recurrent distant metastases (P = 0.028)
      were significantly more frequent in patients with AOG type II; those with AOG
      type II had shorter overall survival than those with type I tumours (P = 0.024).
      Among those with AOG type II, recurrence-free survival was significantly shorter
      after oesophagectomy compared with extended gastrectomy (P = 0.019).
      Thoracoabdominal oesophagectomy had a favourable influence on outcome compared
      with the transhiatal approach. CONCLUSION: Accurate preoperative staging of AOG
      and appropriate surgical therapy are crucial for outcome. AOG type II is a more
      aggressive tumour with higher recurrence rates than AOG type I. These patients
      therefore benefit from more radical surgical treatment.

PMID- 22961521
TI  - Staging and outcome depending on surgical treatment in adenocarcinomas of the
      oesophagogastric junction (Br J Surg 2012; 99: 1406-1414).

PMID- 22961522
TI  - Twenty years of experience with laparoscopic antireflux surgery.
AB  - BACKGROUND: There are few reports of large patient cohorts with long-term follow
      up after laparoscopic antireflux surgery. This study was undertaken to evaluate
      changes in surgical practice and outcomes for laparoscopic antireflux surgery
      over a 20-year period. METHODS: A standardized questionnaire, prospectively
      applied annually, was used to determine outcome for all patients undergoing
      laparoscopic fundoplication in two centres since commencing this procedure in
      1991. Visual analogue scales ranging from 0 to 10 were used to assess symptoms of
      heartburn, dysphagia and satisfaction with overall outcome. Data were analysed to
      determine outcome across 20 years. RESULTS: From 1991 to 2010, 2261 consecutive
      patients underwent laparoscopic fundoplication at the authors' institutions.
      Follow-up ranged from 1 to 19 (mean 7.6) years. Conversion to open surgery
      occurred in 73 operations (3.2 per cent). Revisional surgery was performed in 216
      patients (9.6 per cent), within 12 months of the original operation in 116. There
      was a shift from Nissen to partial fundoplication across 20 years, and a recent
      decline in operations for reflux, offset by an increase in surgery for large
      hiatus hernia. Dysphagia and satisfaction scores were stable, and heartburn
      scores rose slightly across 15 years of follow-up. Heartburn scores were slightly
      higher and reoperation for reflux was more common after anterior partial
      fundoplication (P = 0.005), whereas dysphagia scores were lower and reoperation
      for dysphagia was less common (P < 0.001). At 10 years, satisfaction with outcome
      was similar for all fundoplication types. CONCLUSION: Laparoscopic Nissen and
      partial fundoplications proved to be durable and achieved good long-term
      outcomes. At earlier follow-up, dysphagia was less common but reflux more common
      after anterior partial fundoplication, although differences had largely
      disappeared by 10 years.

PMID- 22961523
TI  - Twenty years of experience with laparoscopic antireflux surgery (Br J Surg 2012;
      99: 1415-1421).

PMID- 22961524
TI  - Caudate lobe-sparing subtotal hepatectomy for primary hepatolithiasis.
AB  - BACKGROUND: Patients with frequent and life-threatening attacks of cholangitis
      due to bilateral primary hepatolithiasis with atrophy of the main liver and giant
      hypertrophy of the caudate lobe were assessed for caudate lobe-sparing subtotal
      hepatectomy. METHODS: This was a retrospective study of prospectively collected
      data from patients who underwent subtotal hepatectomy with sparing of the caudate
      lobe (resection of 7 liver segments, leaving only the caudate lobe) between March
      2003 and December 2009. All patients had concomitant bile duct exploration and
      choledochoscopy. Perioperative and long-term outcomes were analysed. RESULTS:
      Immediate stone clearance was obtained in all 12 patients enrolled in the study.
      Two patients had strictureplasty of the strictured caudate bile duct. There was
      no hospital mortality and six complications developed in three patients. At a
      mean follow-up of 51 months, one patient had developed recurrent stones in the
      caudate lobe bile ducts at 8 months and died from acute purulent cholangitis, 17
      months after surgery. The remaining 11 patients were symptom-free with no further
      attacks of acute cholangitis. CONCLUSION: In selected patients with bilateral
      primary hepatolithiasis, caudate lobe-sparing subtotal hepatectomy is a safe and
      effective treatment.

PMID- 22961525
TI  - Transanal glove port is a safe and cost-effective alternative for transanal
      endoscopic microsurgery.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive
      technique for excision of rectal tumours that avoids conventional pelvic
      resectional surgery along with its risks and side-effects. Although appealing,
      the associated cost and complex learning curve limit TEM utilization by
      colorectal surgeons. Single-port laparoscopic principles are being recognized as
      transferable to transanal work and hybrid techniques are in evolution. Here the
      clinical application of a new technique for transanal access is reported.
      METHODS: Consecutive non-selected patients eligible for TEM over a 3-month period
      (and selected patients thereafter) were offered a procedure performed via a
      'glove TEM port'. This access device was constructed on-table using a circular
      anal dilator (CAD), wound retractor and standard surgical glove, along with
      standard, straight laparoscopic trocar sleeves and instruments. RESULTS: Fourteen
      patients underwent full-thickness resection of benign (8) or malignant (6) rectal
      pathology. CAD insertion failed in one patient and conventional TEM assistance
      was needed in another, leaving 12 procedures completed successfully by glove TEM
      alone as planned (completion rate 86 per cent overall, 92 per cent after
      initiation). The median (range) duration of operation and resected specimen area
      were 93 (30-120) min and 12 (3-152) cm(2) respectively. There was no
      intraoperative and minimal postoperative morbidity, with a median follow-up of
      5.7 (2.7-9.4) months. CONCLUSION: The glove TEM port is a safe, inexpensive and
      readily available access tool that may obviate the use of specialized equipment
      for transanal resection of rectal lesions.

PMID- 22961526
TI  - Transanal glove port is a safe and cost-effective alternative for transanal
      endoscopic microsurgery (Br J Surg 2012; 99: 1429-1435).

PMID- 22961527
TI  - Volume and accreditation, but not specialty, affect quality standards in
      colonoscopy.
AB  - BACKGROUND: The Global Rating Scale, defined by the Joint Advisory Group for
      Gastrointestinal Endoscopy, requires monitoring of endoscopic performance
      indicators. There are known variations in colonoscopic performance, and
      investigation of factors causing this is needed. This study aimed to analyse the
      impact of endoscopist specialty and procedural volume on the quality of
      colonoscopy. METHODS: Data collected prospectively from a UK hospital endoscopy
      service between June 2007 and January 2010 were analysed. The main endpoint was
      the adenoma detection rate (ADR). Secondary endpoints were polyp detection rate
      (PDR), reported caecal intubation rate (CIR) and reported complications.
      Multivariable binary regression models were built to adjust for confounding
      patient-level and endoscopist-level variation. RESULTS: A total of 10,026
      colonoscopies were included, with an overall ADR of 19.2 per cent, a CIR of 90.2
      per cent and a perforation rate of 0.06 per cent. In univariable analyses,
      surgeons had a higher ADR and higher PDR, but lower CIR, compared with
      physicians. Surgeons had a significantly different case mix in terms of age, sex
      and indication for colonoscopy. After adjusting for this case mix in
      multivariable analysis, specialty was no longer a significant predictor of ADR;
      however, surgeons retained their higher PDR and physicians their higher CIR.
      Endoscopists accredited for screening and those performing more than 100
      colonoscopies per year had a higher ADR. CONCLUSION: Adjusting for case mix,
      physicians and surgeons performed equally well in terms of ADR. Accreditation and
      a higher annual number of colonoscopies were more important factors in achieving
      quality standards.

PMID- 22961528
TI  - Randomized double-blind crossover study of alternative stimulator settings in
      sacral nerve stimulation for faecal incontinence.
AB  - BACKGROUND: Sacral nerve stimulation is an established treatment for faecal
      incontinence. Nearly half of all patients experience loss of efficacy at some
      point. Standard reprogramming restores efficacy for some, but not all, patients.
      This study aimed to determine whether alternative stimulator settings would
      increase treatment efficacy. METHODS: Patients with sustained loss of efficacy
      were recruited from two international specialist centres. A number of alternative
      stimulation parameters were tested using a double-blind randomized crossover
      study design. Stimulation settings tested were pulse frequencies of 6.9 and 31
      Hz, and pulse widths of 90 and 330 us, compared with one standard setting of 14
      Hz/210 us. Treatment efficacy was evaluated using a disease-specific quality-of
      life score (Fecal Incontinence Quality of Life Scale, FIQLS) and a bowel habit
      diary completed before randomization, during the study period and after 3 months
      of follow-up with one preferred setting. RESULTS: Fifteen patients were analysed.
      With one preferred setting, three of four subdomains in the FIQLS improved
      significantly. The mean(s.d.) total number of incontinence episodes dropped from
      11.7(10.8) to 4.8(4.5) per 3 weeks (P = 0.011) and improvements were maintained
      after 3 months of follow-up. Optimal pacemaker settings were individual, but a
      trend towards highest patient satisfaction and improved treatment outcome was
      evident for high-frequency stimulation (31 Hz/210 us), which was preferred by
      eight of the 15 patients. CONCLUSION: Patients experiencing loss of efficacy can
      experience improvement if alternative pacemaker settings are tested. High
      frequency stimulation (31 Hz/210 us) was preferred by more than half of the
      patients, and improved treatment outcome was sustained at 3 months.

PMID- 22961529
TI  - Outcome of abdominosacral resection for locally advanced primary and recurrent
      rectal cancer.
AB  - BACKGROUND: The aim was to assess the indications for and outcomes of
      abdominosacral resection for patients with locally advanced primary and recurrent
      rectal cancer. METHODS: Consecutive patients undergoing abdominosacral resection
      between January 2006 and December 2011 were identified from a prospectively
      maintained database. The main endpoints were 3-year local recurrence-free (LRFS)
      and disease-free (DFS) survival. RESULTS: Thirty patients underwent
      abdominosacral resection, 22 for recurrent rectal cancer and eight for locally
      advanced primary cancer. Sacrectomy was performed at S1/2 in five, S3 in 11 and
      S4/5 in 14 patients. R0 resection was achieved in 23 patients; all seven positive
      margins (R1) were in patients with recurrent disease. There were no deaths in
      hospital or within 30 days. S1/2 sacrectomy was associated with the highest rate
      of major complications (60 per cent versus 27 and 29 per cent for S3 and S4/5
      respectively) and long-term complications (60, 36 and 14 per cent). Overall 3
      year LRFS was 66 per cent and 3-year DFS was 55 per cent. Both were significantly
      better in patients with negative compared with positive margins (LRFS: 87 versus
      0 per cent, P < 0.001; DFS: 71 versus 0 per cent, P = 0.033). CONCLUSION:
      Abdominosacral resection was associated with long-term survival in carefully
      selected patients with advanced rectal cancer. Postoperative complications were
      common and often multiple. Sacrectomy for locally advanced primary rectal cancer
      was associated with a low margin-positive rate and should be considered as an
      acceptable treatment. Margin-positive resection was associated with poor survival
      outcomes and should be avoided.

PMID- 22961530
TI  - Systematic review and meta-analysis of randomized clinical trials of self
      expanding metallic stents as a bridge to surgery versus emergency surgery for
      malignant left-sided large bowel obstruction (Br J Surg 2012; 99: 469-476).

PMID- 22961533
TI  - Rectal perforation with life-threatening peritonitis following stapled
      haemorrhoidopexy (Br J Surg 2012; 99: 746-753).

PMID- 22961534
TI  - Systematic review and meta-analysis of randomized clinical trials of self
      expanding metallic stents as a bridge to surgery versus emergency surgery for
      malignant left-sided large bowel obstruction (Br J Surg 2012; 99: 469-476).

PMID- 22961537
TI  - Image-guided surgical navigation in otology.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of image-guided surgical
      navigation (IGSN) in otologic surgery and establish practice guidelines. STUDY
      DESIGN: Prospective study. METHODS: Between January 2003 and January 2010, all
      patients requiring complicated surgery for chronic otitis media, glomus jugulare,
      atresia, cerebrospinal fluid leak with or without encephalocele, and cholesterol
      granuloma of the petrous apex were offered IGSN. The accuracy of IGSN relative to
      pertinent pathology and 11 anatomic landmarks was established. Additionally IGSN
      related operative time, complications, and surgical outcome were recorded.
      RESULTS: In the study period there were 820 otologic procedures, among 94
      patients (96 ears) with disease meeting proposed criteria. Thirteen patients (15
      procedures) consented to the use of IGSN. All patients had a minimum 6 months of
      follow-up. The average additional operative time required was 36.7 minutes. The
      mean accuracy error was 1.1 mm laterally at the tragus but decreased to 0.8 mm
      medially at the level of the oval window. The mean accuracy of IGSN was within 1
      mm in 10 of the 11 targeted surgical anatomic landmarks. CONCLUSIONS: Interactive
      image-guided surgical navigation during complex otologic surgery may improve
      surgical outcome and decrease morbidity by providing an accurate real-time
      display of surgical instrumentation relative to patient anatomy and pathology. In
      select cases, the extra cost of imaging immediately prior to surgery and extra
      operating room time may be compensated by enhancing the ability to distinguish
      distorted anatomy relative to disease, potentially improving surgical outcome.
      IGSN, although useful, does not replace surgical expertise and experience.

PMID- 22961539
TI  - Brain. Editorial.

PMID- 22961538
TI  - Early postoperative healing following buccal single flap approach to access
      intraosseous periodontal defects.
AB  - AIM: This study aims to evaluate the early postoperative healing of papillary
      incision wounds and its association with (1) patient/site-related factors and
      technical (surgical) aspects as well as with (2) 6-month clinical outcomes
      following buccal single flap approach (SFA) in the treatment of intraosseous
      periodontal defects. METHODS: Forty-three intraosseous defects in 35 patients
      were accessed with a buccal SFA alone or in combination with a reconstructive
      technology (graft, enamel matrix derivative (EMD), graft + EMD, or graft +
      membrane). Postoperative healing was evaluated at 2 weeks using the Early Wound
      Healing Index (EHI). RESULTS: EHI ranged from score 1 (i.e., complete flap
      closure and optimal healing) to score 4 (i.e., loss of primary closure and
      partial tissue necrosis). SFA resulted in a complete wound closure at 2 weeks in
      the great majority of sites. A significantly more frequent presence of
      interdental contact point and interdental soft tissue crater, and narrower base
      of the interdental papilla were observed at sites with either EHI > 1 or EHI = 4
      compared to sites with EHI = 1. No association between EHI and the 6-month
      clinical outcomes was observed. CONCLUSIONS: At 2 weeks, buccal SFA may result in
      highly predictable complete flap closure. CLINICAL RELEVANCE: Site-specific
      characteristics may influence the early postoperative healing of the papillary
      incision following SFA procedure. Two-week soft tissue healing, however, was not
      associated with the 6-month clinical outcomes.

PMID- 22961540
TI  - Vascular endothelial growth factor and HDAC 6: a neuroprotective signalling
      pathway against cancer therapy-induced neuropathy.

PMID- 22961541
TI  - Testing upper motor neuron function in amyotrophic lateral sclerosis: the most
      difficult task of neurophysiology.

PMID- 22961542
TI  - Delirium, dementia and senility.

PMID- 22961544
TI  - Pathophysiology of protein aggregation and extended phenotyping in filaminopathy.
AB  - Mutations in FLNC cause two distinct types of myopathy. Disease associated with
      mutations in filamin C rod domain leading to expression of a toxic protein
      presents with progressive proximal muscle weakness and shows focal destructive
      lesions of polymorphous aggregates containing desmin, myotilin and other proteins
      in the affected myofibres; these features correspond to the profile of
      myofibrillar myopathy. The second variant associated with mutations in the actin
      binding domain of filamin C is characterized by weakness of distal muscles and
      morphologically by non-specific myopathic features. A frameshift mutation in the
      filamin C rod domain causing haploinsufficiency was also found responsible for
      distal myopathy with some myofibrillar changes but no protein aggregation typical
      of myofibrillar myopathies. Controversial data accumulating in the literature
      require re-evaluation and comparative analysis of phenotypes associated with the
      position of the FLNC mutation and investigation of the underlying disease
      mechanisms. This is relevant and necessary for the refinement of diagnostic
      criteria and developing therapeutic approaches. We identified a p.W2710X mutation
      in families originating from ethnically diverse populations and re-evaluated a
      family with a p.V930_T933del mutation. Analysis of the expanded database allows
      us to refine clinical and myopathological characteristics of myofibrillar
      myopathy caused by mutations in the rod domain of filamin C. Biophysical and
      biochemical studies indicate that certain pathogenic mutations in FLNC cause
      protein misfolding, which triggers aggregation of the mutant filamin C protein
      and subsequently involves several other proteins. Immunofluorescence analyses
      using markers for the ubiquitin-proteasome system and autophagy reveal that the
      affected muscle fibres react to protein aggregate formation with a highly
      increased expression of chaperones and proteins involved in proteasomal protein
      degradation and autophagy. However, there is a noticeably diminished efficiency
      of both the ubiquitin-proteasome system and autophagy that impairs the muscle
      capacity to prevent the formation or mediate the degradation of aggregates.
      Transfection studies of cultured muscle cells imitate events observed in the
      patient's affected muscle and therefore provide a helpful model for testing
      future therapeutic strategies.

PMID- 22961545
TI  - Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in'
      mice.
AB  - Mucolipidosis II is a neurometabolic lysosomal trafficking disorder of infancy
      caused by loss of mannose 6-phosphate targeting signals on lysosomal proteins,
      leading to lysosomal dysfunction and accumulation of non-degraded material.
      However, the identity of storage material and mechanisms of neurodegeneration in
      mucolipidosis II are unknown. We have generated 'knock-in' mice with a common
      mucolipidosis II patient mutation that show growth retardation, progressive brain
      atrophy, skeletal abnormalities, elevated lysosomal enzyme activities in serum,
      lysosomal storage in fibroblasts and brain and premature death, closely mimicking
      the mucolipidosis II disease in humans. The examination of affected mouse brains
      at different ages by immunohistochemistry, ultrastructural analysis,
      immunoblotting and mass spectrometric analyses of glycans and anionic lipids
      revealed that the expression and proteolytic processing of distinct lysosomal
      proteins such as alpha-l-fucosidase, beta-hexosaminidase, alpha-mannosidase or
      Niemann-Pick C2 protein are more significantly impacted by the loss of mannose 6
      phosphate residues than enzymes reaching lysosomes independently of this
      targeting mechanism. As a consequence, fucosylated N-glycans, GM2 and GM3
      gangliosides, cholesterol and bis(monoacylglycero)phosphate accumulate
      progressively in the brain of mucolipidosis II mice. Prominent astrogliosis and
      the accumulation of organelles and storage material in focally swollen axons were
      observed in the cerebellum and were accompanied by a loss of Purkinje cells.
      Moreover, an increased neuronal level of the microtubule-associated protein 1
      light chain 3 and the formation of p62-positive neuronal aggregates indicate an
      impairment of constitutive autophagy in the mucolipidosis II brain. Our findings
      demonstrate the essential role of mannose 6-phosphate for selected lysosomal
      proteins to maintain the capability for degradation of sequestered components in
      lysosomes and autophagolysosomes and prevent neurodegeneration. These lysosomal
      proteins might be a potential target for a valid therapeutic approach for
      mucolipidosis II disease.

PMID- 22961546
TI  - Hypoperfusion predicts lesion progression in cerebral X-linked
      adrenoleukodystrophy.
AB  - Magnetic resonance imaging sequences such as diffusion and spectroscopy have been
      well studied in X-linked adrenoleukodystrophy, but no data exist on magnetic
      resonance perfusion imaging. Since inflammation is known to modulate the
      microcirculation, we investigated the hypothesis that changes in the local
      perfusion might be one of the earliest signs of lesion development. Twenty
      patients with different phenotypes of adrenoleukodystrophy and seven age-matched
      controls were evaluated between 2006 and 2011. Fluid attenuated inversion
      recovery, post-contrast T(1)-weighted and normalized dynamic susceptibility
      contrast magnetic resonance perfusion cerebral blood volume maps were co
      registered, segmented when cerebral lesion was present, and normalized cerebral
      blood volume values were analysed using a Food and Drug Association approved
      magnetic resonance perfusion software (NordicICE). Clinical and imaging data were
      reviewed to determine phenotype and status of progression. All eight patients
      with cerebral adrenoleukodystrophy had an average 80% decrease in normalized
      cerebral blood volume at the core of the lesion (P < 0.0001). Beyond the leading
      edge of contrast enhancement cerebral perfusion varied, patients with progressive
      lesions showed an average 60% decrease in normalized cerebral blood volume
      (adults P < 0.05; children P < 0.001), while one child with arrested progression
      normalized cerebral blood volume in this region. In six of seven patients with
      cerebral adrenoleukodystrophy lesions and follow-up imaging (2-24 month interval
      period), we found progression of contrast enhancement into the formerly
      hypoperfused perilesional zone. Asymptomatic, adrenomyeloneuropathy and female
      heterozygote patients had no significant changes in cerebral perfusion. Our data
      indicate that decreased brain magnetic resonance perfusion precedes leakage of
      the blood-brain barrier as demonstrated by contrast enhancement in cerebral
      adrenoleukodystrophy and is an early sign of lesion progression.

PMID- 22961543
TI  - Neurological perspectives on voltage-gated sodium channels.
AB  - The activity of voltage-gated sodium channels has long been linked to disorders
      of neuronal excitability such as epilepsy and chronic pain. Recent genetic
      studies have now expanded the role of sodium channels in health and disease, to
      include autism, migraine, multiple sclerosis, cancer as well as muscle and immune
      system disorders. Transgenic mouse models have proved useful in understanding the
      physiological role of individual sodium channels, and there has been significant
      progress in the development of subtype selective inhibitors of sodium channels.
      This review will outline the functions and roles of specific sodium channels in
      electrical signalling and disease, focusing on neurological aspects. We also
      discuss recent advances in the development of selective sodium channel
      inhibitors.

PMID- 22961547
TI  - Early-onset Lafora body disease.
AB  - The most common progressive myoclonus epilepsies are the late infantile and late
      infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6
      years), Unverricht-Lundborg disease (onset after the age of 6 years) and Lafora
      disease. Lafora disease is a distinct disorder with uniform course: onset in
      teenage years, followed by progressively worsening myoclonus, seizures, visual
      hallucinations and cognitive decline, leading to a vegetative state in status
      myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are
      pathognomonic and not seen with any other progressive myoclonus epilepsies.
      Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen
      molecules with inordinately long strands that render them insoluble. Lafora
      disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin
      phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically
      active enzymes that regulate glycogen construction, ensuring symmetric expansion
      into a spherical shape, essential to its solubility. In this work, we report a
      new progressive myoclonus epilepsy associated with Lafora bodies, early-onset
      Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and
      mutation and characterize the relationship of its gene product with laforin and
      malin. Early-onset Lafora body disease presents early, at 5 years, with
      dysarthria, myoclonus and ataxia. The combination of early-onset and early
      dysarthria strongly suggests late infantile-variant neuronal ceroid
      lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis,
      but Lafora bodies. The subsequent course is a typical progressive myoclonus
      epilepsy, though much more protracted than any infantile neuronal ceroid
      lipofuscinosis, or Lafora disease, patients living into the fourth decade. The
      mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show
      that the PRDM8 protein interacts with laforin and malin and causes translocation
      of the two proteins to the nucleus. We find that Phe261Leu-PRDM8 results in
      excessive sequestration of laforin and malin in the nucleus and that it therefore
      likely represents a gain-of-function mutation that leads to an effective
      deficiency of cytoplasmic laforin and malin. We have identified a new progressive
      myoclonus epilepsy with Lafora bodies, early-onset Lafora body disease, 101 years
      after Lafora disease was first described. The results to date suggest that PRDM8,
      the early-onset Lafora body disease protein, regulates the cytoplasmic quantities
      of the Lafora disease enzymes.

PMID- 22961548
TI  - Anterior insular cortex is necessary for empathetic pain perception.
AB  - Empathy refers to the ability to perceive and share another person's affective
      state. Much neuroimaging evidence suggests that observing others' suffering and
      pain elicits activations of the anterior insular and the anterior cingulate
      cortices associated with subjective empathetic responses in the observer.
      However, these observations do not provide causal evidence for the respective
      roles of anterior insular and anterior cingulate cortices in empathetic pain.
      Therefore, whether these regions are 'necessary' for empathetic pain remains
      unknown. Herein, we examined the perception of others' pain in patients with
      anterior insular cortex or anterior cingulate cortex lesions whose locations
      matched with the anterior insular cortex or anterior cingulate cortex clusters
      identified by a meta-analysis on neuroimaging studies of empathetic pain
      perception. Patients with focal anterior insular cortex lesions displayed
      decreased discrimination accuracy and prolonged reaction time when processing
      others' pain explicitly and lacked a typical interference effect of empathetic
      pain on the performance of a pain-irrelevant task. In contrast, these deficits
      were not observed in patients with anterior cingulate cortex lesions. These
      findings reveal that only discrete anterior insular cortex lesions, but not
      anterior cingulate cortex lesions, result in deficits in explicit and implicit
      pain perception, supporting a critical role of anterior insular cortex in
      empathetic pain processing. Our findings have implications for a wide range of
      neuropsychiatric illnesses characterized by prominent deficits in higher-level
      social functioning.

PMID- 22961549
TI  - PTEN deletion enhances survival, neurite outgrowth and function of dopamine
      neuron grafts to MitoPark mice.
AB  - Clinical trials in Parkinson's disease have shown that transplants of embryonic
      mesencephalic dopamine neurons form new functional connections within the host
      striatum, but the therapeutic benefits have been highly variable. One obstacle
      has been poor survival and integration of grafted dopamine neurons. Activation of
      Akt, a serine/threonine kinase that promotes cell survival and growth, increases
      the ability of neurons to survive after injury and to regenerate lost neuronal
      connections. Because the lipid phosphatase, phosphatase and tensin homolog (PTEN)
      inhibits Akt, we generated a mouse with conditional knock-out of PTEN in dopamine
      neurons, leading to constitutive expression of Akt in these neurons. Ventral
      mesencephalic tissue from dopamine phosphatase and tensin homologue knock-out or
      control animals was then transplanted bilaterally into the dopamine depleted
      striata of MitoPark mice that express a parkinsonian phenotype because of severe
      respiratory chain dysfunction in dopamine neurons. After transplantation into
      MitoPark mice, PTEN-deficient dopamine neurons were less susceptible to cell
      death, and exhibited a more extensive pattern of fibre outgrowth compared to
      control grafts. Voltammetric measurements demonstrated that dopamine release and
      reuptake were significantly increased in the striata of animals receiving
      dopamine PTEN knock-out transplants. These animals also displayed enhanced
      spontaneous and drug-induced locomotor activity, relative to control transplanted
      MitoPark mice. Our results suggest that disinhibition of the Akt-signalling
      pathway may provide a valuable strategy to enhance survival, function and
      integration of grafted dopamine neurons within the host striatum and, more
      generally, to improve survival and integration of different forms of neural
      grafts.

PMID- 22961551
TI  - Neuropathological correlates of dopaminergic imaging in Alzheimer's disease and
      Lewy body dementias.
AB  - Investigation of dopaminergic transporter loss in vivo using (123)I-N
      fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon
      emission computed tomography has been widely used as a diagnostic aid in Lewy
      body disease. However, it is not clear whether the pathological basis for the
      imaging changes observed reflects loss of dopaminergic transporter expressing
      neurons because of cell death or dysfunctional neurons due to possible nigral
      and/or striatal neurodegenerative pathology. We aimed to investigate the
      influence of nigral neuronal loss as well as nigral (alpha-synuclein, tau) and
      striatal (alpha-synuclein, tau, amyloid beta) pathology on striatal uptake in a
      cohort of autopsy-confirmed Alzheimer's disease (n = 4), dementia with Lewy
      bodies (n = 7) and Parkinson's disease dementia (n = 12) cases. Subjects
      underwent ante-mortem dopaminergic scanning and post-mortem assessments (mean
      interval 3.7 years). Striatal binding (caudate, anterior and posterior putamen)
      was estimated using region of interest procedures while quantitative
      neuropathological measurements of alpha-synuclein, tau and amyloid beta were
      carried out. Similarly, nigral neuronal density was assessed quantitatively.
      Stepwise linear regression was performed to identify significant pathological
      predictors of striatal binding. In all striatal regions, image uptake was
      associated with nigral dopaminergic neuronal density (P <= 0.04) but not alpha
      synuclein (P >= 0.46), tau (P >= 0.18) or amyloid beta (P >= 0.22) burden. The
      results suggest that reduced uptake in vivo may be influenced considerably by
      neuronal loss rather than the presence of pathological lesions, in particular
      those related to Alzheimer's disease and Lewy body dementias. However,
      dysfunctional nigral neurons may have an additional effect on striatal uptake in
      vivo but their respective role remains to be elucidated.

PMID- 22961550
TI  - Cholinergic dysfunction contributes to gait disturbance in early Parkinson's
      disease.
AB  - Gait disturbance is an early feature in Parkinson's disease. Its pathophysiology
      is poorly understood; however, cholinergic dysfunction may be a non-dopaminergic
      contributor to gait. Short-latency afferent inhibition is a surrogate measure of
      cholinergic activity, allowing the contribution of cholinergic dysfunction to
      gait to be evaluated. We hypothesized that short-latency afferent inhibition
      would be an independent predictor of gait dysfunction in early Parkinson's
      disease. Twenty-two participants with Parkinson's disease and 22 age-matched
      control subjects took part in the study. Gait was measured objectively using an
      instrumented walkway (GAITRite), and subjects were asked to walk at their
      preferred speed for 2 min around a 25-m circuit. Spatiotemporal characteristics
      (speed, stride length, stride time and step width) and gait dynamics (variability
      described as the within subject standard deviation of: speed, stride time, stride
      length and step width) were determined. Short-latency afferent inhibition was
      measured by conditioning motor evoked potentials, elicited by transcranial
      magnetic stimulation of the motor cortex, with electrical stimuli delivered to
      the contralateral median nerve at intervals ranging from N20 (predetermined) to
      N20 + 4 ms. Short-latency afferent inhibition was determined as the percentage
      difference between test and conditioned response for all intervals and was
      described as the group mean. Participants were optimally medicated at the time of
      testing. Participants with Parkinson's disease had significantly reduced gait
      speed (P = 0.002), stride length (P = 0.008) and stride time standard deviation
      (P = 0.001). Short-latency afferent inhibition was also significantly reduced in
      participants with Parkinson's disease (P = 0.004). In participants with
      Parkinson's disease, but not control subjects, significant associations were
      found between gait speed, short-latency afferent inhibition, age and postural
      instability and gait disorder score (Movement Disorders Society Unified
      Parkinson's Disease Rating Scale) and attention, whereas global cognition and
      depression were marginally significant. No other gait variables were associated
      with short-latency afferent inhibition. A multiple hierarchical regression model
      explored the contribution of short-latency afferent inhibition to gait speed,
      controlling for age, posture and gait symptoms (Postural Instability and Gait
      Disorder score-Movement Disorders Society Unified Parkinson's Disease Rating
      Scale), attention and depression. Regression analysis in participants with
      Parkinson's disease showed that reduced short-latency afferent inhibition was an
      independent predictor of slower gait speed, explaining 37% of variability. The
      final model explained 72% of variability in gait speed with only short-latency
      afferent inhibition and attention emerging as independent determinants. The
      results suggest that cholinergic dysfunction may be an important and early
      contributor to gait dysfunction in Parkinson's disease. The findings also point
      to the contribution of non-motor mechanisms to gait dysfunction. Our study
      provides new insights into underlying mechanisms of non-dopaminergic gait
      dysfunction, and may help to direct future therapeutic approaches.

PMID- 22961552
TI  - Decreased carbon-11-flumazenil binding in early Alzheimer's disease.
AB  - Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment
      than amyloid deposition, is currently gauged by the degree of regional atrophy.
      However, functional markers, such as GABA(A) receptor density, a marker of
      neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A)
      messenger RNA expression is reduced even in mild cognitive impairment. We
      measured whole-brain GABA(A) binding potential in vivo using [(11)C]-flumazenil
      positron emission tomography and compared GABA(A) binding with metabolic and
      volumetric measurements. For this purpose, we studied 12 subjects, six patients
      with early Alzheimer's disease and six healthy controls, with [(11)C]-flumazenil
      and [(18)F]-fluorodeoxyglucose positron emission tomography, as well as with high
      resolution magnetic resonance imaging. Data were evaluated with both voxel-based
      parametric methods and volume of interest methods. We found that in early
      Alzheimer's disease, with voxel-based analysis, [(11)C]-flumazenil binding was
      decreased in infero-medial temporal cortex, retrosplenial cortex and posterior
      perisylvian regions. Inter-group differences reached corrected significance when
      using an arterial input function. Metabolism measured with positron emission
      tomography and volumetric measurements obtained with magnetic resonance imaging
      showed changes in regions affected in early Alzheimer's disease, but, unlike with
      [(11)C]-flumazenil binding and probably due to sample size, the voxel-based
      findings failed to reach corrected significance in any region of the brain. With
      volume of interest analysis, hippocampi and posterior cingulate gyrus showed
      decreased [(11)C]-flumazenil binding. In addition, [(11)C]-flumazenil hippocampal
      binding correlated with memory performance. Remarkably, [(11)C]-flumazenil
      binding was decreased precisely in the regions showing the greatest degree of
      neuronal loss in post-mortem studies of early Alzheimer's disease. From these
      data, we conclude that [(11)C]-flumazenil binding could be a useful marker of
      neuronal loss in early Alzheimer's disease.

PMID- 22961553
TI  - Immunoglobulin G Fc receptor deficiency prevents Alzheimer-like pathology and
      cognitive impairment in mice.
AB  - Alzheimer's disease is a severely debilitating disease of high and growing
      proportions. Hypercholesterolaemia is a key risk factor in sporadic Alzheimer's
      disease that links metabolic disorders (diabetes, obesity and atherosclerosis)
      with this pathology. Hypercholesterolaemia is associated with increased levels of
      immunoglobulin G against oxidized lipoproteins. Patients with Alzheimer's disease
      produce autoantibodies against non-brain antigens and specific receptors for the
      constant Fc region of immunoglobulin G have been found in vulnerable neuronal
      subpopulations. Here, we focused on the potential role of Fc receptors as
      pathological players driving hypercholesterolaemia to Alzheimer's disease. In a
      well-established model of hypercholesterolaemia, the apolipoprotein E knockout
      mouse, we report increased brain levels of immunoglobulin G and upregulation of
      activating Fc receptors, predominantly of type IV, in neurons susceptible to
      amyloid beta accumulation. In these mice, gene deletion of gamma-chain, the
      common subunit of activating Fc receptors, prevents learning and memory
      impairments without influencing cholesterolaemia and brain and serum
      immunoglobulin G levels. These cognition-protective effects were associated with
      a reduction in synapse loss, tau hyperphosphorylation and intracellular amyloid
      beta accumulation both in cortical and hippocampal pyramidal neurons. In vitro,
      activating Fc receptor engagement caused synapse loss, tau hyperphosphorylation
      and amyloid beta deposition in primary neurons by a mechanism involving mitogen
      activated protein kinases and beta-site amyloid precursor protein cleaving enzyme
      1. Our results represent the first demonstration that immunoglobulin G Fc
      receptors contribute to the development of hypercholesterolaemia-associated
      features of Alzheimer's disease and suggest a new potential target for slowing or
      preventing Alzheimer's disease in hypercholesterolaemic patients.

PMID- 22961554
TI  - The mitochondrial calcium regulator cyclophilin D is an essential component of
      oestrogen-mediated neuroprotection in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder that is
      more prevalent in males than in females. A similar gender difference has been
      reported in some strains of transgenic mouse models of familial amyotrophic
      lateral sclerosis harbouring the G93A mutation in CuZn superoxide dismutase.
      Mitochondrial damage caused by pathological alterations in Ca(2+) accumulation is
      frequently involved in neurodegenerative diseases, including CuZn superoxide
      dismutase-related amyotrophic lateral sclerosis, but its association with gender
      is not firmly established. In this study, we examined the effects of genetic
      ablation of cyclophilin D on gender differences in mice expressing G93A mutant
      CuZn superoxide dismutase. Cyclophilin D is a mitochondrial protein that promotes
      mitochondrial damage from accumulated Ca(2+). As anticipated, we found that
      cyclophilin D ablation markedly increased Ca(2+) retention in brain mitochondria
      of both males and females. Surprisingly, cyclophilin D ablation completely
      abolished the phenotypic advantage of G93A females, with no effect on disease in
      males. We also found that the 17beta-oestradiol decreased Ca(2+) retention in
      brain mitochondria, and that cyclophilin D ablation abolished this effect.
      Furthermore, 17beta-oestradiol protected G93A cortical neurons and spinal cord
      motor neurons against glutamate toxicity, but the protection was lost in neurons
      lacking cyclophilin D. Taken together, these results identify a novel mechanism
      of oestrogen-mediated neuroprotection in CuZn superoxide dismutase-related
      amyotrophic lateral sclerosis, whereby Ca(2+) overload and mitochondrial damage
      are prevented in a cyclophilin D-dependent manner. Such a protective mechanism
      may contribute to the lower incidence and later onset of amyotrophic lateral
      sclerosis, and perhaps other chronic neurodegenerative diseases, in females.

PMID- 22961555
TI  - DNA methylation signatures of peripheral leukocytes in schizophrenia.
AB  - Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity
      rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in
      several studies. However, no comprehensive studies using medication-free subjects
      with SCZ have been conducted. In addition, most of these studies have been
      limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene
      promoter regions, so little is known about the DNA methylation signatures across
      the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG
      sites) of peripheral leukocytes was conducted in the first set of samples (24
      medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium
      HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed
      using three pairs of monozygotic twins that were discordant for SCZ. Finally, the
      data from these two independent cohorts were compared. A total of 234
      differentially methylated CpG sites that were common between these two cohorts
      were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the
      CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf:
      11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them
      were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'
      UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci
      across the whole genome in peripheral leukocytes using two independent sets of
      samples. These findings support the notion that altered DNA methylation could be
      involved in the pathophysiology of SCZ.

PMID- 22961556
TI  - Solute carrier family 2 member 1 is involved in the development of nonalcoholic
      fatty liver disease.
AB  - Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic
      bases, but the associated variants are uncertain. The aim of the present study
      was to identify genetic variants that could help to prognose and further
      understand the genetics and development of NAFLD. Allele frequencies of 3,072
      single-nucleotide polymorphisms (SNPs) in 92 genes were characterized in 69 NAFLD
      patients and 217 healthy individuals. The markers that showed significant allele
      frequency differences in the pilot groups were subsequently studied in 451 NAFLD
      patients and 304 healthy controls. Besides this, 4,414 type 2 diabetes mellitus
      (T2DM) cases and 4,567 controls were genotyped. Liver expression of the
      associated gene was measured and the effect of its potential role was studied by
      silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and
      the consequences of oleic acid (OA)-enriched medium on lipid accumulation in
      siSLC2A1-THLE2 cells were studied by gene-expression analysis, dihydroethidium
      staining, BODIPY, and quantification of intracellular triglyceride content,
      respectively. Several SNPs of SLC2A1 (solute carrier family 2 [facilitated
      glucose transporter] member 1) showed association with NAFLD, but not with T2DM,
      being the haplotype containing the minor allele of SLC2A1 sequence related to the
      susceptibility to develop NAFLD. Gene-expression analysis demonstrated a
      significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional
      analyses of transcriptome profiles drove us to demonstrate that in vitro
      silencing of SLC2A1 induces an increased OS activity and a higher lipid
      accumulation under OA treatment. CONCLUSIONS: Genetic variants of SLC2A1 are
      associated with NAFLD, and in vitro down-regulation of this gene promotes lipid
      accumulation. Moreover, the oxidative response detected in siSLC2A1-THLE2 cells
      corroborated the antioxidant properties previously related to this gene and
      linked the most representative clinical characteristics of NAFLD patients:
      oxidative injury and increased lipid storage.

PMID- 22961558
TI  - Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie
      Tooth neuropathy.
AB  - BACKGROUND: Mutations in inverted formin, FH2, and WH2 domain containing (INF2)
      are common causes of dominant focal segmental glomerulosclerosis. INF2 encodes a
      member of the diaphanous-related formin family, which regulates actin and
      microtubule cytoskeletons. Charcot-Marie-Tooth neuropathy (CMT) is a group of
      inherited disorders affecting peripheral neurons. Many reports have shown that
      glomerulopathy can associate with CMT. However, it has been unclear whether these
      two processes in the same individual represent one disorder or if they are two
      separate diseases. CASE DIAGNOSIS/TREATMENT: Recently, INF2 mutations were
      identified in 12 of 16 patients with CMT-associated glomerulopathy, suggesting
      that these mutations are a common cause of the dual phenotype. In this study, we
      report two cases of CMT-associated glomerulopathy that both showed INF2
      mutations. A novel INF2 mutation, p. L77P, was identified in a family in which
      the dual phenotype was inherited in a dominant fashion. The pathogenic effect of
      p. L77P was proposed using a structural homology model. In addition, we
      identified a patient with a sporadic CMT-associated glomerulopathy carrying a
      known INF2 mutation: p. L128P. CONCLUSIONS: Our study confirms the link between
      INF2 mutations and CMT-associated glomerulopathy and widens the spectrum of
      pathogenic mutations.

PMID- 22961557
TI  - Decreased cerebellar fiber density in cortical myoclonic tremor but not in
      essential tremor.
AB  - Pathophysiology of tremor generation remains uncertain in 'familial cortical
      myoclonic tremor with epilepsy' (FCMTE) and essential tremor (ET). In both
      disorders, imaging and pathological studies suggest involvement of the cerebellum
      and its projection areas. MR diffusion tensor imaging allows estimation of white
      matter tissue composition, and therefore is well suited to quantify structural
      changes in vivo. This study aimed to compare cerebellar fiber density between
      FCMTE and ET patients and healthy controls. Seven FCMTE patients, eight ET
      patients, and five healthy controls were studied. Cerebellum was annotated based
      on fractional anisotropy (FA) and mean diffusivity volumes. Mean cerebellar FA
      values were computed as well as mean cerebellar volume. Group statistics included
      one-way ANOVAs and post hoc independent t tests. Mean FA of the cerebellar region
      for FCMTE was 0.242 (SD = 0.012), for ET 0.259 (SD = 0.0115), and for controls
      0.262 (SD = 0.0146). There was a significant group effect for FA (F(2) = 4.9, p =
      0.02). No difference in mean cerebellar volume was found. Post hoc independent t
      tests revealed significantly decreased mean FA in FCMTE patients compared to
      controls (t[10] = 2.5, p = 0.03) and ET patients (t[13] = 2.9, p = 0.01), while
      there was no difference in mean FA between ET patients and controls (t[11] <
      1.0). This study indicates for the first time microstructural damage of the
      cerebellar white matter in FCMTE in vivo. These results ascertain a role of the
      cerebellum in 'cortical tremor'.

PMID- 22961559
TI  - Distribution of polycyclic aromatic hydrocarbons in surface water and sediment
      near a drinking water reservoir in Northeastern China.
AB  - The levels of polycyclic aromatic hydrocarbons (PAHs) in the water and the
      sediment samples collected near the Mopanshan Reservoir-the most important
      drinking water resource of Harbin City in Northeast China-were examined. A total
      of 16 PAHs were concurrently identified and quantified in the three water bodies
      tested (Lalin River, Mangniu River, and Mopanshan Reservoir) and in the Mopanshan
      drinking water treatment plant during the high- and low water periods. The total
      PAH concentrations in the water and sediment samples ranged from 122.7 to 639.8
      ng/L and from 89.1 to 749.0 ng/g dry weight, respectively. Similar spatial and
      temporal trends were also found for both samples. The lowest Sigma16PAH
      concentration of the Mopanshan Reservoir was obtained during the high water
      period; by contrast, the Lalin River had the highest concentration during the low
      water period. The PAH profiles resembling the three water bodies, with high
      percentages of low-molecular weight PAHs and dominated by two- to three-ring PAHs
      (78.4 to 89.0%). Two of the molecular indices used reflected the possible PAH
      sources, indicating the main input from coal combustion, especially during the
      low water period. The conventional drinking water treatment operations resulted
      in a 20.7 to 67.0% decrease in the different-ringed PAHs in the Mopanshan-treated
      drinking water. These findings indicate that human activities negatively affect
      the drinking water resource. Without the obvious removal of the PAHs in the
      waterworks, drinking water poses certain potential health risks to people.

PMID- 22961560
TI  - The Forum of the International HCH and Pesticides Association--a platform for
      international cooperation.
AB  - The unsustainable life cycle management of pesticides in the last 60 years has
      created large pesticide stockpiles. The two major working areas of the
      International HCH and Pesticide Association (IHPA; www.ihpa.info ) address a part
      of these legacies and are shortly introduced here: (1) The assessment and support
      of the management of the worlds single largest POPs stockpile: the globally
      dumped 4 to 7 million tonnes hexachlorocyclohexane (HCH) wastes from lindane
      production, and (2) the support for the management of the obsolete pesticides
      legacy in Eastern Europe, the Caucasus and Central Asia (EECCA) countries of
      ~240,000 t, leaving these pesticides in unregulated storages without adequate
      safety control being a huge risk to the environment and human health. The
      integrative approach IHPA takes-promoting international cooperation and the
      exchange of knowledge and experiences-is shortly explained. IHPA has developed
      various supporting tools for its work: the IHPA web page and newsletter informing
      on the threats and challenges, but also on the progresses of managing pesticide
      stockpiles; the joint GIZ-PAN-IHPA exhibition on awareness of the pesticide
      stockpile challenge; and the 'International HCH and Pesticides Forum' as most
      important tool to progress the integrative work and mission of IHPA. Finally, a
      summary of the 11th International HCH and Pesticides Forum held in Gabala,
      Azerbaijan is given which brought together more than 120 scientists, policy
      makers, non-governmental and international organisations, industry and students
      from more than 40 countries to progress the obsolete pesticides and hazardous
      chemical waste challenge in EECCA countries. The event finished with adoption of
      'Gabala Declaration', which aims to mobilise efforts of all stakeholders for
      prevention and elimination of POPs, obsolete pesticides, and hazardous chemical
      waste in the region.

PMID- 22961561
TI  - Brassica napus hairy roots and rhizobacteria for phenolic compounds removal.
AB  - Phenolic compounds are contaminants frequently found in water and soils. In the
      last years, some technologies such as phytoremediation have emerged to remediate
      contaminated sites. Plants alone are unable to completely degrade some
      pollutants; therefore, their association with rhizospheric bacteria has been
      proposed to increase phytoremediation potential, an approach called
      rhizoremediation. In this work, the ability of two rhizobacteria, Burkholderia
      kururiensis KP 23 and Agrobacterium rhizogenes LBA 9402, to tolerate and degrade
      phenolic compounds was evaluated. Both microorganisms were capable of tolerating
      high concentrations of phenol, 2,4-dichlorophenol (2,4-DCP), guaiacol, or
      pentachlorophenol (PCP), and degrading different concentrations of phenol and 2,4
      DCP. Association of these bacterial strains with B. napus hairy roots, as model
      plant system, showed that the presence of both rhizospheric microorganisms, along
      with B. napus hairy roots, enhanced phenol degradation compared to B. napus hairy
      roots alone. These findings are interesting for future applications of these
      strains in phenol rhizoremediation processes, with whole plants, providing an
      efficient, economic, and sustainable remediation technology.

PMID- 22961562
TI  - Choline supply of preterm infants: assessment of dietary intake and
      pathophysiological considerations.
AB  - BACKGROUND: Choline forms the head group of phosphatidylcholines, comprising 40
      50 % of cellular membranes and 70-95 % of phospholipids in surfactant, bile, and
      lipoproteins. Moreover, choline serves as the precursor of acetylcholine and is
      important for brain differentiation and function. While accepted as essential for
      fetal and neonatal development, its role in preterm infant nutrition has not yet
      gained much attention. METHODS: The adequate intake of choline of preterm infants
      was estimated from international recommendations for infants, children, and
      adults. Choline intake relative to other nutrients was determined retrospectively
      in all inborn infants below 1,000 g (extremely low birth weight) or below 28
      weeks gestational age, admitted to our department in 2006 and 2007 (N = 93).
      RESULTS: Estimation of adequate intake showed that children with 290 g body
      weight need more choline than those with 1,200 g (31.4 and 25.2 mg/kg/day,
      respectively). Day-by-day variability was high for all nutrient intakes including
      choline. In contrast to the continuous intrauterine choline delivery, median
      supply reached a plateau at d11 (21.7 mg/kg/day; 25th/75th percentile: 19.6;
      23.9). Individual choline supply at d0-d1 and d2-d3 was <10 mg/kg/day in 100 and
      69 % of infants, respectively. Furthermore, intakes <10 mg/kg/day were frequently
      observed beyond day 11. Median adequate intakes (27.4 mg/kg/day at 735 g body
      weight) were achieved in <2 %. CONCLUSIONS: Nutritional intake of choline in this
      cohort of preterm infants was frequently less than the estimated adequate intake,
      with particular shortage until postnatal d10. Because choline is important for
      brain development, future studies are needed to investigate the effects of
      adequate nutritional choline intake on long-term neurodevelopment in VLBW
      infants.

PMID- 22961563
TI  - Aqueous extract of Terminalia arjuna attenuates tert-butyl hydroperoxide-induced
      oxidative stress in HepG2 cell model.
AB  - Arjuna (Terminalia arjuna) is a medicinal plant used in many polyherbal
      hepatoprotective formulations. Although widely claimed to be antioxidant, data
      supporting such actions of Arjuna are limited. In the present study, we have
      investigated the efficacy of the aqueous extract of T. arjuna (AETA) using a
      standard pro-oxidant [tertiary butyl hydroperoxide (TBHP)] in HepG2 cells. Cells
      were incubated with AETA (5-100 ug/ml) for a range of time points (4-24 h) with
      or without TBHP (500 MUM), and biochemical markers of oxidative stress (OS) were
      determined. Cells incubated with TBHP showed the significant induction of OS
      response in cytosol manifested as lipid hydroperoxide (76%-198%) and the
      generation of reactive oxygen species (60%-127%). Diminished levels of reduced
      glutathione (35%-60%) and total antioxidant capacity (20%-61%) suggested an
      altered redox state. Significant perturbations in the activities of antioxidant
      enzymes such as catalase (30%-56%), superoxide dismutase (25%-68%), glutathione S
      transferase (29%-67%), glutathione peroxidase (24%-68%) and glutathione reductase
      (38%-49%) were discernible suggesting the ongoing OS in the cells. However, cells
      treated with AETA (100 ug/ml) along with TBHP offered significant protection by
      reducing levels of lipid hydroperoxide (33%-62%) and ROS (69%) and by increasing
      antioxidant capacity (54%-81%) and levels of reduced glutathione (49%-82%).
      Further, it also enhanced the activities of endogenous antioxidant enzymes
      (superoxide dismutase, 60%; catalase, 35%-82%; glutathione peroxidase, 42-65 %;
      glutathione reductase, 48%-62%; and glutathione S-transferase, 22%-100%). Taken
      together, these data suggest that Arjuna can protect against the oxidative damage
      induced by TBHP and may be effectively used as a hepatoprotective adjuvant to
      abrogate OS in vivo.

PMID- 22961564
TI  - Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer
      patients: a mechanism of proliferation and apoptosis in cancer.
AB  - Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates
      embryological pancreas development and insulin expression in adult islets. The
      current study investigated the expression profile and potential role of PDX-1 in
      breast cancer. Immunohistochemistry was performed to determine the expression
      pattern of PDX-1 in breast cancer and adjacent benign breast tissues. In
      addition, cell proliferation and the cell cycle were evaluated following the
      transient inhibition of PDX-1 with antisense oligonucleotides in MCF-7 human
      breast cancer cells. Real-time PCR and western blotting were conducted to
      investigate the correlation between PDX-1, P53, Ki-67, Caspase 3 and Caspase 8.
      These experiments demonstrated that PDX-1 was downregulated in human breast
      cancer tissue compared with adjacent normal breast tissue. Knockdown of PDX-1
      expression in vitro in MCF-7 breast cancer cells promoted cell proliferation and
      disrupted the cell cycle, as demonstrated by the overexpression of P53 and Ki-67
      at the mRNA and protein levels. In conclusion, the current study shows that PDX-1
      regulates cell proliferation and the cell cycle in human breast cancer cells by
      altering the expression of the cell cycle-related genes, P53 and Ki-67. These
      data suggest that PDX-1 is a putative tumor suppressor in breast cancer.

PMID- 22961565
TI  - Cancer net survival on registry data: use of the new unbiased Pohar-Perme
      estimator and magnitude of the bias with the classical methods.
AB  - Net survival, the survival which might occur if cancer was the only cause of
      death, is a major epidemiological indicator required for international or
      temporal comparisons. Recent findings have shown that all classical methods used
      for routine estimation of net survival from cancer-registry data, sometimes
      called "relative-survival methods," provide biased estimates. Meanwhile, an
      unbiased estimator, the Pohar-Perme estimator (PPE), was recently proposed. Using
      real data, we investigated the magnitude of the errors made by four "relative
      survival" methods (Ederer I, Hakulinen, Ederer II and a univariable regression
      model) vs. PPE as reference and examined the influence of time of follow-up,
      cancer prognosis, and age on the errors made. The data concerned seven cancer
      sites (2,51,316 cases) collected by FRANCIM cancer registries. Net survivals were
      estimated at 5, 10 and 15 years postdiagnosis. At 5 years, the errors were
      generally small. At 10 years, in good-prognosis cancers, the errors made in
      nonstandardized estimates with all classical methods were generally great (+2.7
      to +9% points in prostate cancer) and increased in age-class estimations (vs. 5
      year ones). At 15 years, in bad- or average-prognosis cancers, the errors were
      often substantial whatever the nature of the estimation. In good-prognosis
      cancers, the errors in nonstandardized estimates of all classical methods were
      great and sometimes very important. With all classical methods, great errors
      occurred in age-class estimates resulting in errors in age-standardized estimates
      (+0.4 to +3.2% points in breast cancer). In estimating net survival, cancer
      registries should abandon all classical methods and adopt the new Pohar-Perme
      estimator.

PMID- 22961566
TI  - Vitamin D status is associated with physical performance: the results of three
      independent cohorts.
AB  - This study, on the association between vitamin D status and physical performance
      and its decline, shows that vitamin D status is associated with physical
      performance in several older age groups. However, vitamin D status does not
      predict a decline in physical performance in individuals aged 55-65 years.
      INTRODUCTION: Previous research in the Longitudinal Aging Study Amsterdam (LASA)
      showed an association of vitamin D status with physical performance and its
      decline in persons aged 65 years and older. The current study aims to determine
      these associations in younger individuals and to replicate previous research of
      LASA. METHODS: Data from three independent cohorts were used: two cohorts of LASA
      (LASA-II with measurements in 2002 (n = 707) and 2009 (n = 491), LASA-I-2009 (n =
      355)) and the baseline measurement of the B-Vitamins for the Prevention of
      Osteoporotic Fractures (B-PROOF) study (n = 2,813). Participants performed three
      tests (walking test, chair stands, and tandem stand; range total score 0-12),
      except in LASA-II-2002 (only walking and chair stands tests; range total score 0
      8). Multiple linear and logistic regression were used to assess whether vitamin D
      status was associated with total physical performance and its decline,
      respectively. RESULTS: The mean age of the participants was 60.0 (SD 3.0), 65.9
      (2.9), 78.4 (5.3), and 74.4 (6.8) years for LASA-II-2002, LASA-II-2009, LASA-I
      2009, and B-PROOF, respectively. Vitamin D status was not predictive of a
      clinical decline in total physical performance score in the LASA-II-2002 cohort
      (aged 55-65 years). After adjustment for confounding, participants with serum
      25(OH)D < 50 nmol/L scored 0.8 (95 % confidence interval 0.4-1.2), 0.9 (0.3-1.5),
      1.5 (0.8-2.3), and 0.6 (0.3-0.9) points lower on total physical performance than
      participants with serum 25(OH)D >= 75 nmol/L. CONCLUSION: Our study confirmed
      that serum 25(OH)D is associated with physical performance. However, vitamin D
      status did not predict a clinical decline in physical performance in individuals
      aged 55-65 years.

PMID- 22961567
TI  - Assessment of inflammatory and oxidative biomarkers in obesity and their
      associations with body mass index.
AB  - The aim of this study was to evaluate the inflammatory and oxidative biomarkers'
      levels in obese subjects and their associations with body mass index (BMI), in
      order to investigate the role of these biomarkers in obesity. Fasting glucose,
      total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides,
      apolipoprotein A, apolipoprotein B, albumin, urinary albumin, creatinine,
      glomerular filtration rate, interleukin-6 (IL-6), nitrate/nitrite (NOx), and
      ischemia-modified albumin (IMA) were measured in 93 subjects divided according to
      different BMI. IL-6, urinary albumin, and IMA levels were significantly higher in
      obese subjects. However, the levels of NOx were significantly lower in this
      population. Significant correlations between BMI and IL-6 (r = 0.326, P = 0.002),
      NOx (r = -0.249, P = 0.021), urinary albumin (r = 0.270, P = 0.008), and IMA (r =
      0.286, P = 0.005) were reported. We have shown an increase of IL-6, urinary
      albumin, and IMA combined with lower levels of NOx in obese patients and an
      association between of these biomarkers with BMI, suggesting a possible interplay
      of oxidative stress, inflammation, and endothelial dysfunction state in obesity.

PMID- 22961568
TI  - Iron metabolism is associated with adipocyte insulin resistance and plasma
      adiponectin: the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study.
AB  - OBJECTIVE: Adipocyte insulin resistance (IR) is a key feature early in the
      pathogenesis of type 2 diabetes mellitus (T2DM), and although scarce, data in the
      literature suggest a direct role for iron and iron metabolism-related factors in
      adipose tissue function and metabolism. Serum ferritin and transferrin were shown
      to be associated with muscle insulin resistance (IR) and T2DM, but little is
      known about the role of iron metabolism on adipose tissue. We therefore
      investigated whether markers of iron metabolism were associated with adipocyte IR
      and plasma adiponectin. RESEARCH DESIGN AND METHODS: Serum ferritin, transferrin,
      total iron, non-transferrin-bound iron (NTBI), transferrin saturation, and plasma
      adiponectin were determined in 492 individuals. Adipocyte IR was defined by the
      product of fasting insulin and nonesterified fatty acids (NEFAs). Using linear
      regression analyses, we investigated the difference in adipocyte IR or
      adiponectin (in %) according to differences in iron metabolism markers. RESULTS:
      Serum ferritin (beta = 1.00% increase in adipocyte IR per 10 MUg/L [95% CI 0.66
      1.34]), transferrin (4.18% per 0.1 g/L [2.88-5.50]), total iron (1.36% per
      MUmol/L [0.61-2.12]), and NTBI (5.14% per MUmol/L [1.88-8.52]) were associated
      with adipocyte IR after adjustment for several covariates, including inflammatory
      markers. All markers of iron metabolism were also associated with NEFAs (all P <
      0.01). In addition, ferritin and transferrin were inversely associated with
      adiponectin (both P < 0.01). CONCLUSIONS: The observed associations of several
      markers of iron metabolism with adipocyte IR and adiponectin suggest that factors
      related to iron and iron metabolism may contribute to adipocyte IR early in the
      pathogenesis of T2DM.

PMID- 22961569
TI  - Diabetes-related behaviors in Latinas and non-Latinas in California.
AB  - OBJECTIVE: Certain dietary and physical activity behaviors have been associated
      with the risk of developing type 2 diabetes, yet little is known about the
      prevalence of these behaviors among Latinas (Latino women). The purpose of this
      cross-sectional study was to compare the prevalence of diabetes-related behaviors
      in Latinas and non-Latinas. RESEARCH DESIGN AND METHODS: Using data from the 2009
      California Health Interview Survey, we compared self-reported diabetes-related
      behaviors of Latinas (n = 4,321) to non-Latinas (n = 21,112) after excluding
      women who were pregnant or had diabetes. For six behaviors, we determined the cut
      point for the least healthy tertile: walking, doing moderate to vigorous physical
      activity, and consuming fried potatoes, sugar-sweetened beverages (SSBs),
      desserts, and fast food. We used logistic regression to examine the association
      between Latina ethnicity and being in the least healthy tertile compared with the
      other two tertiles for each of these behaviors. RESULTS: In multivariate models
      adjusted for age, income, education, marital status, health status, smoking, and
      acculturation, Latinas had a higher risk (odds ratio [95% CI]) of being in the
      least healthy tertile for the consumption of fast food (1.94 [1.63-2.31]), SSBs
      (1.53 [1.29-1.82]), and fried potatoes (1.32 [1.18-1.67]), and lower risk for
      desserts (0.82 [0.70-0.95]). Latinas and non-Latinas had similar physical
      activity levels. CONCLUSIONS: Dietary differences between Latinas and non-Latinas
      (particularly in the consumption of fast food and SSBs) may be the focus of
      interventions to prevent diabetes in Latinas. Further research among Latinas is
      needed to understand and modify these dietary behaviors.

PMID- 22961570
TI  - Reduced heart rate variability among youth with type 1 diabetes: the SEARCH CVD
      study.
AB  - OBJECTIVE: This study compared heart rate variability (HRV) parameters in youth
      with and without type 1 diabetes and explored potential contributors of altered
      HRV. RESEARCH DESIGN AND METHODS: HRV parameters were measured among 354 youth
      with type 1 diabetes (mean age 18.8 years, diabetes duration 9.8 years, and mean
      A1C 8.9%) and 176 youth without diabetes (mean age 19.2 years) participating in
      the SEARCH CVD study. Multiple linear regression was used to assess the
      relationship between diabetes status and HRV parameters, adjusting for
      covariates. RESULTS: Compared with control subjects, youth with type 1 diabetes
      had reduced overall HRV (10.09 ms lower SD of NN intervals [SDNN]) and markers of
      parasympathetic loss (13.5 ms reduced root mean square successive difference of
      NN intervals [RMSSD] and 5.2 normalized units (n.u.) reduced high frequency [HF]
      power) with sympathetic override (5.2 n.u. increased low frequency [LF] power),
      independent of demographic, anthropometric, and traditional cardiovascular risk
      factors. Older age, female sex, higher LDL cholesterol and triglyceride levels,
      and presence of microalbuminuria were independently associated with lower HRV but
      did not account for the observed differences between youth with and without
      diabetes. Youth with type 1 diabetes and A1C levels >=7.5% had significantly
      worse HRV parameters than control subjects; however, in youth with optimal
      glycemic control (A1C <7.5%), HRV parameters did not differ significantly from
      control subjects. CONCLUSIONS: Youth with type 1 diabetes have signs of early
      cardiac autonomic neuropathy: reduced overall HRV and parasympathetic loss with
      sympathetic override. The main driver of these subclinical abnormalities appears
      to be hyperglycemia.

PMID- 22961571
TI  - Insulin regimens and clinical outcomes in a type 1 diabetes cohort: the SEARCH
      for Diabetes in Youth study.
AB  - OBJECTIVE: To examine the patterns and associations of insulin regimens and
      change in regimens with clinical outcomes in a diverse population of children
      with recently diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS: The study
      sample consisted of youth with type 1 diabetes who completed a baseline SEARCH
      for Diabetes in Youth study visit after being newly diagnosed and at least one
      follow-up visit. Demographic, diabetes self-management, physical, and laboratory
      measures were collected at study visits. Insulin regimens and change in regimen
      compared with the initial visit were categorized as more intensive (MI), no
      change (NC), or less intensive (LI). We examined relationships between insulin
      regimens, change in regimen, and outcomes including A1C and fasting C-peptide.
      RESULTS: Of the 1,606 participants with a mean follow-up of 36 months, 51.7%
      changed to an MI regimen, 44.7% had NC, and 3.6% changed to an LI regimen.
      Participants who were younger, non-Hispanic white, and from families of higher
      income and parental education and who had private health insurance were more
      likely to be in MI or NC groups. Those in MI and NC groups had lower baseline A1C
      (P = 0.028) and smaller increase in A1C over time than LI (P < 0.01). Younger
      age, continuous subcutaneous insulin pump therapy, and change to MI were
      associated with higher probability of achieving target A1C levels. CONCLUSIONS:
      Insulin regimens were intensified over time in over half of participants but
      varied by sociodemographic domains. As more intensive regimens were associated
      with better outcomes, early intensification of management may improve outcomes in
      all children with diabetes. Although intensification of insulin regimen is
      preferred, choice of insulin regimen must be individualized based on the child
      and family's ability to comply with the prescribed plan.

PMID- 22961572
TI  - White blood cells count and incidence of type 2 diabetes in young men.
AB  - OBJECTIVE: Association between white blood cell (WBC) count and diabetes risk has
      been recently suggested. We assessed whether WBC count is an independent risk
      factor for diabetes incidence among young healthy adults. RESEARCH DESIGN AND
      METHODS: WBC count was measured in 24,897 young (mean age 30.8 +/- 5.36 years),
      normoglycemic men with WBC range of 3,000 to 12,000 cells/mm(3). Participants
      were periodically screened for diabetes during a mean follow-up of 7.5 years.
      RESULTS: During 185,354 person-years of follow-up, diabetes was diagnosed in 447
      subjects. A multivariate model adjusted for age, BMI, family history of diabetes,
      physical activity, and fasting glucose and triglyceride levels revealed a 7.6%
      increase in incident diabetes for every increment of 1,000 cells/mm(3) (P =
      0.046). When grouped in quintiles, a baseline WBC count above 6,900 cells/mm(3)
      had an independent 52% increase in diabetes risk (hazard ratio 1.52 [95% CI 1.06
      2.18]) compared with the lowest quintile (WBC <5,400 cells/mm(3)). Men at the
      lowest WBC quintile were protected from diabetes incidence even in the presence
      of overweight, family history of diabetes, or elevated triglyceride levels. After
      simultaneous control for risk factors, BMI was the primary contributor of the
      variation in multivariate models (P < 0.001), followed by age and WBC count (P <
      0.001), and family history of diabetes and triglyceride levels (P = 0.12).
      CONCLUSIONS: WBC count, a commonly used and widely available test, is an
      independent risk factor for diabetes in young men at values well within the
      normal range.

PMID- 22961573
TI  - Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2
      diabetic women with delayed gastric emptying: pharmacokinetics and
      pharmacodynamics.
AB  - OBJECTIVE: To investigate the pharmacokinetics (PK), pharmacodynamics, and safety
      of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal
      symptoms (GCSI) and previously documented delayed gastric emptying (DGE).
      RESEARCH DESIGN AND METHODS: In a randomized crossover study, 10 female patients
      received RM-131 (100 MUg s.c.) or placebo and underwent scintigraphic gastric
      emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal
      administered 30 min postdosing. Adverse events, plasma glucose, and hormonal
      levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments.
      PK was assessed in this cohort and healthy volunteers (HVs). RESULTS: At
      screening, HbA(1c) was 7.2 +/- 0.4% (SEM) and total GCSI-DD score was 1.32 +/-
      0.21. RM-131 accelerated GE t(1/2) of solids (P = 0.011); mean difference (Delta)
      in solid GE t(1/2) was 68.3 min (95% CI 20-117) or 66.1%. There were numerical
      differences in GE lag time, CF6 solids, and GE t(1/2) liquids (all P < 0.14).
      With a significant (P < 0.014) order effect, further analysis of the first
      treatment period (n = 5 per group) confirmed significant RM-131 effects on GE
      t(1/2) (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in
      DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as
      well as 30-90-min area under the curve (AUC) levels of growth hormone, cortisol,
      and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was
      reported more on RM-131. CONCLUSIONS: RM-131 greatly accelerates the GE of solids
      in patients with type 2 diabetes and documented DGE. PK is similar in diabetic
      patients and HVs.

PMID- 22961574
TI  - Early microvascular recruitment modulates subsequent insulin-mediated skeletal
      muscle glucose metabolism during lipid infusion.
AB  - OBJECTIVE: To test whether early, insulin-mediated microvascular recruitment in
      skeletal muscle predicts steady-state glucose metabolism in the setting of
      physiological elevation of free fatty acid concentrations. RESEARCH DESIGN AND
      METHODS: We measured insulin's microvascular and metabolic effects in 14 healthy
      young adults during a 2-h euglycemic insulin clamp. Plasma free fatty acid
      concentrations were raised (Intralipid and heparin infusion) for 3 h before the
      clamp and maintained at postprandial concentrations during the clamp.
      Microvascular blood volume (MBV) was measured by contrast-enhanced ultrasound
      (CEU) continuously from baseline through the first 30 min of the insulin clamp.
      Muscle glucose and insulin uptake were measured by the forearm balance method.
      RESULTS: The glucose infusion rate (GIR) necessary to maintain euglycemia during
      the clamp varied by fivefold across subjects (2.5-12.5 mg/min/kg). The early MBV
      responses to insulin, as indicated by CEU video intensity, ranged widely, from a
      39% decline to a 69% increase. During the clamp, steady state forearm muscle
      glucose uptake and GIR each correlated significantly with the change in forearm
      MBV (P < 0.01). To explore the basis for the wide range of vascular and metabolic
      insulin sensitivity observed, we also measured V(O(2max)) in a subset of eight
      subjects. Fitness (V(O(2max))) correlated significantly with the GIR, the forearm
      glucose uptake, and the percentage change in MBV during the insulin clamp (P <
      0.05 for each). CONCLUSIONS: Early microvascular responses to insulin strongly
      associate with steady state skeletal muscle insulin-mediated glucose uptake.
      Physical fitness predicts both metabolic and vascular insulin responsiveness.

PMID- 22961575
TI  - Public health implications of recommendations to individualize glycemic targets
      in adults with diabetes.
AB  - OBJECTIVE: To estimate how many U.S. adults with diabetes would be eligible for
      individualized A1C targets based on 1) the 2012 American Diabetes Association
      (ADA) guideline and 2) a published approach for individualized target ranges.
      RESEARCH DESIGN AND METHODS: We studied adults with diabetes >=20 years of age
      from the National Health and Nutrition Examination Survey 2007-2008 (n = 757). We
      assigned A1C targets based on duration, age, diabetes-related complications, and
      comorbid conditions according to 1) the ADA guideline and 2) a strategy by Ismail
      Beigi focused on setting target ranges. We estimated the number and proportion of
      adults with each A1C target and compared individualized targets to measured
      levels. RESULTS: Using ADA guideline recommendations, 31% (95% CI 27-34%) of the
      U.S. adult diabetes population would have recommended A1C targets of <7.0%, and
      69% (95% CI 66-73%) would have A1C targets less stringent than <7.0%. Using the
      Ismail-Beigi strategy, 56% (51-61%) would have an A1C target of <=7.0%, and 44%
      (39-49%) would have A1C targets less stringent than <7.0%. If a universal A1C
      <7.0% target were applied, 47% (41-54%) of adults with diabetes would have
      inadequate glycemic control; this proportion declined to 30% (26-36%) with the
      ADA guideline and 31% (27-36%) with the Ismail-Beigi strategy. CONCLUSIONS: Using
      individualized glycemic targets, about half of U.S. adults with diabetes would
      have recommended A1C targets of >=7.0% but one-third would still be considered
      inadequately controlled. Diabetes research and performance measurement goals will
      need to be revised in order to encourage the individualization of glycemic
      targets.

PMID- 22961576
TI  - LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during
      critical illness: the LOGIC-1 single-center, randomized, controlled clinical
      trial.
AB  - OBJECTIVE: Tight blood glucose control (TGC) in critically ill patients is
      difficult and labor intensive, resulting in poor efficacy of glycemic control and
      increased hypoglycemia rate. The LOGIC-Insulin computerized algorithm has been
      developed to assist nurses in titrating insulin to maintain blood glucose levels
      at 80-110 mg/dL (normoglycemia) and to avoid severe hypoglycemia (<40 mg/dL). The
      objective was to validate clinically LOGIC-Insulin relative to TGC by experienced
      nurses. RESEARCH DESIGN AND METHODS: The investigator-initiated LOGIC-1 study was
      a prospective, parallel-group, randomized, controlled clinical trial in a single
      tertiary referral center. A heterogeneous mix of 300 critically ill patients were
      randomized, by concealed computer allocation, to either nurse-directed glycemic
      control (Nurse-C) or algorithm-guided glycemic control (LOGIC-C). Glycemic
      penalty index (GPI), a measure that penalizes both hypoglycemic and hyperglycemic
      deviations from normoglycemia, was the efficacy outcome measure, and incidence of
      severe hypoglycemia (<40 mg/dL) was the safety outcome measure. RESULTS: Baseline
      characteristics of 151 Nurse-C patients and 149 LOGIC-C patients and study times
      did not differ. The GPI decreased from 12.4 (interquartile range 8.2-18.5) in
      Nurse-C to 9.8 (6.0-14.5) in LOGIC-C (P < 0.0001). The proportion of study time
      in target range was 68.6 +/- 16.7% for LOGIC-C patients versus 60.1 +/- 18.8% for
      Nurse-C patients (P = 0.00016). The proportion of severe hypoglycemic events was
      decreased in the LOGIC-C group (Nurse-C 0.13%, LOGIC-C 0%; P = 0.015) but not
      when considered as a proportion of patients (Nurse-C 3.3%, LOGIC-C 0%; P =
      0.060). Sampling interval was 2.2 +/- 0.4 h in the LOGIC-C group versus 2.5 +/-
      0.5 h in the Nurse-C group (P < 0.0001). CONCLUSIONS: Compared with expert
      nurses, LOGIC-Insulin improved efficacy of TGC without increasing rate of
      hypoglycemia.

PMID- 22961577
TI  - Microstructural white matter abnormalities and cognitive functioning in type 2
      diabetes: a diffusion tensor imaging study.
AB  - OBJECTIVE: To examine whether type 2 diabetes is associated with microstructural
      abnormalities in specific cerebral white matter tracts and to relate these
      microstructural abnormalities to cognitive functioning. RESEARCH DESIGN AND
      METHODS: Thirty-five nondemented older individuals with type 2 diabetes (mean age
      71 +/- 5 years) and 35 age-, sex-, and education-matched control subjects
      underwent a 3 Tesla diffusion-weighted MRI scan and a detailed cognitive
      assessment. Tractography was performed to reconstruct several white matter
      tracts. Diffusion tensor imaging measures, including fractional anisotropy (FA)
      and mean diffusivity (MD), were compared between groups and related to cognitive
      performance. RESULTS: MD was significantly increased in all tracts in both
      hemispheres in patients compared with control subjects (P < 0.05), reflecting
      microstructural white matter abnormalities in the diabetes group. Increased MD
      was associated with slowing of information-processing speed and worse memory
      performance in the diabetes but not in the control group after adjustment for
      age, sex, and estimated IQ (group * MD interaction, all P < 0.05). These
      associations were independent of total white matter hyperintensity load and
      presence of cerebral infarcts. CONCLUSIONS: Individuals with type 2 diabetes
      showed microstructural abnormalities in various white matter pathways. These
      abnormalities were related to worse cognitive functioning.

PMID- 22961578
TI  - Sagittal abdominal diameter as a new predictor for incident diabetes.
AB  - OBJECTIVE: Obesity, particularly visceral adiposity, is a major risk factor for
      type 2 diabetes. The commonly used obesity indicators, BMI, waist girth, and
      waist-to-hip ratio (WHR), have limited ability to measure the visceral adipose
      tissue. Sagittal abdominal diameter (SAD) has been shown to predict the amount of
      visceral fat. So far no study has been published on its ability to predict
      diabetes occurrence. RESEARCH DESIGN AND METHODS: We assessed and compared the
      prediction of the four obesity indicators for diabetes incidence in a prospective
      study based on 5,168 participants from the nationally representative Health 2000
      study. RESULTS: During a mean follow-up lasting 8.1 years, 222 incident diabetes
      cases occurred. In multivariate models adjusted for lifestyle factors, BMI, waist
      girth, WHR, and SAD were significant predictors of diabetes incidence. The
      relative risks (95% CI) between high and low levels were 15.0 (6.94-32.6), 11.4
      (5.39-23.8), 12.5 (6.47-24.2), and 14.7 (6.89-31.2), respectively. Pairwise
      interaction analysis showed that the co-occurrence of high BMI and high SAD was
      associated with the highest diabetes incidence, with a relative risk of 37.0
      (11.2-122). After adjustment for waist girth and the components of the metabolic
      syndrome, the relative risk was 9.88 (2.81-34.7). The corresponding population
      attributable fraction estimate was 84% (49-95). CONCLUSIONS: The combination of
      SAD and BMI measurements yields a new predictor of diabetes incidence.

PMID- 22961579
TI  - Estimation of the glycation gap in diabetic patients with stable glycemic
      control.
AB  - OBJECTIVE: The glycation gap (the difference between measured A1C and the value
      predicted by regression on fructosamine) is stable and is associated with
      microvascular complications of diabetes but has not hitherto been estimated
      within a clinically useful time frame. We investigated whether two determinations
      30 days apart suffice for a reasonably reliable estimate if both A1C and
      fructosamine exhibit stability. RESEARCH DESIGN AND METHODS: We studied 311
      patients with type 1 or type 2 diabetes for whom simultaneous measurements of A1C
      and serum fructosamine had been made on at least two occasions separated by 1
      month (t(0) and t(1)). Glycemia was deemed stable if A1C(t(1)) - A1C(t(0)) and
      fructosamine(t(1)) - fructosamine(t(0)) were both less than their reference
      change values (RCVs). Instantaneous glycation gaps [gg(t(0)) and gg(t(1))] and
      their mean (GG), were calculated using the data from all stable patients for the
      required regression. RESULTS: Stable glycemia was shown by 144 patients. In 90%
      of unstable case subjects, a change in medication was identified as the cause of
      instability. Among 129 stable patients with an average of eight gg determinations
      prior to t(0), GG correlated closely with the mean of these prior determinations
      (r(2) = 0.902, slope 1.025, intercept -0.038). CONCLUSIONS: The glycation gap can
      be calculated reliably from pairs of A1C and fructosamine measurements taken 1
      month apart if these measurements satisfy the RCV criteria for glycemic control.

PMID- 22961580
TI  - Efficacy of metabolic and psychological screening for mood disorders among
      children with type 1 diabetes.
AB  - OBJECTIVE: To compare the diagnostic accuracy and time expenditure of screening
      models based on glycated hemoglobin (HbA(1c)) level and psychometric measures for
      mood disorder (MD) among children with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: With semistructured clinical interviews (Schedule for Affective
      Disorders and Schizophrenia for Children-Present and Lifetime version, 120
      min/patient) as a reference for diagnosing MD, including major depressive
      disorder (MDD), we tested 163 subjects, aged 8 to 18 years, with type 1 diabetes.
      We evaluated four screening approaches: 1) Children's Depression Inventory (CDI)
      at 30 min/patient, 2) HbA(1c) level, 3) HbA(1c) level plus CDI, and 4) HbA(1c)
      level plus Children's Depression Rating Scale (CDRS) at 40 min/patient. These
      tests were conducted with all participants, and the total time expenditure for
      all four approaches was calculated as the total time needed to implement
      successfully the screening for MD or MDD in the center. RESULTS: HbA(1c)
      performed on par with individual psychometric tests in diagnosing MD or MDD. The
      HbA(1c) plus CDRS model was the best screening procedure for both MD and MDD,
      with diagnostic thresholds for HbA(1c) established at 8.7% and 9.0%,
      respectively. Cutoff points for CDRS assessed after filtering by HbA(1c) were 26
      (MD) and 30 (MDD) points. Center-wide application of this procedure would result
      in an 83% reduction of the examination time necessary for the psychiatrist for MD
      screening and a 91% reduction for MDD screening, as compared with standard
      screening with CDI. CONCLUSIONS: Use of HbA(1c) level followed by CDRS is a time
      efficient procedure to screen for MD in children with type 1 diabetes.

PMID- 22961582
TI  - HIV disease burden and related risk behaviours among men who have sex with men in
      Yuxi Prefecture, Yunnan Province, China: 2010-2011.
AB  - The HIV epidemic is rapidly increasing among men who have sex with men (MSM) in
      China. Data on the disease burden and risk behaviours of MSM related to HIV
      transmission are needed to inform education and prevention programs. We conducted
      two cross-sectional surveys among MSM in Yuxi Prefecture in Yunnan Province,
      China, during 2010-2011. Men were recruited by snowball (participant referrals)
      and nomination sampling methods at gay-oriented venues and hotspots. Participants
      were asked to complete a 20-min anonymous questionnaire. Blood samples were
      collected to determine HIV status and the BED capture enzyme immunoassay was used
      to estimate the incidence rate. A total of 288 MSM participated in this study
      across the two surveys. The two-year overall HIV prevalence was 10.7 % and the
      estimated incidence rate was 5.4 per 100 person-years (95 % CI 1.1-9.6). A
      reported 37.2 % of MSM were married to a female and 35.1 % had sex with a female
      in the past 6 months. Condom use with male partners (81.4-93.0 %) and female
      partners (56.3-77.4 %) at the last penetrative act significantly increased
      between the survey conducted in 2010 and the survey in 2011. HIV prevalence is
      high among Chinese MSM in Yunnan. Common bisexual behaviours and low consistent
      condom use with female partners suggest a potential spread of HIV from MSM to
      females. 

PMID- 22961581
TI  - Counselling, case management and health promotion for people living with
      HIV/AIDS: an overview of systematic reviews.
AB  - Our objective was to identify all existing systematic reviews related to
      counselling, case management and health promotion for people living with
      HIV/AIDS. For the reviews identified, we assessed the quality and local
      applicability to support evidence-informed policy and practice. We searched 12
      electronic databases and two reviewers independently assessed the 5,398
      references retrieved from our searches and included 18 systematic reviews. Each
      review was categorized according to the topic(s) addressed, quality appraised and
      summarized by extracting key messages, the year searches were last completed and
      the countries in which included studies were conducted. Twelve reviews address
      topics related to counselling and case management (mean quality score of 6.5/11).
      Eight reviews (mean quality score of 6/11) address topics related to health
      promotion (two address both domains). The findings from this overview of
      systematic reviews provide a useful resource for supporting the development and
      delivery of evidence-informed support services in community settings.

PMID- 22961583
TI  - Weekending in PLWH: alcohol use and ART adherence, a pilot study.
AB  - We examined alcohol use patterns and adherence to antiretroviral therapy (ART)
      among 45 people living with HIV (PLWH) in Miami, Florida. Documented provider
      knowledge of alcohol use was also assessed. Among our sample, 20 % reported
      "weekending," a phenomenon we describe as skipping ART due to planned alcohol use
      and drinking more on the weekend. While 100 % of our sample reported alcohol use,
      73 % of providers' notes reported abstinence. Until larger studies assess the
      generalizability of these findings among other PLWH, providers should consider
      probing patients about when they drink, how much they drink, and if they take ART
      when drinking.

PMID- 22961584
TI  - Vacuum-assisted cell loading enables shear-free mammalian microfluidic culture.
AB  - Microfluidic perfusion cultures for mammalian cells provide a novel means for
      probing single-cell behavior but require the management of culture parameters
      such as flow-induced shear stress. Methods to eliminate shear stress generally
      focus on capturing cells in regions with high resistance to fluid flow. Here, we
      present a novel trapping design to easily and reliably load a high density of
      cells into culture chambers that are extremely isolated from potentially damaging
      flow effects. We utilize a transient on-chip vacuum to remove air from the
      culture chambers and rapidly replace the volume with a liquid cell suspension. We
      demonstrate the ability of this simple and robust method to load and culture
      three commonly used cell lines. We show how the incorporation of an on-chip
      function generator can be used for dynamic stimulation of cells during long-term
      continuous perfusion culture.

PMID- 22961585
TI  - Delineation and validation of river network spatial scales for water resources
      and fisheries management.
AB  - Identifying appropriate spatial scales is critically important for assessing
      health, attributing data, and guiding management actions for rivers. We describe
      a process for identifying a three-level hierarchy of spatial scales for Michigan
      rivers. Additionally, we conduct a variance decomposition of fish occurrence,
      abundance, and assemblage metric data to evaluate how much observed variability
      can be explained by the three spatial scales as a gage of their utility for water
      resources and fisheries management. The process involved the development of
      geographic information system programs, statistical models, modification by
      experienced biologists, and simplification to meet the needs of policy makers.
      Altogether, 28,889 reaches, 6,198 multiple-reach segments, and 11 segment classes
      were identified from Michigan river networks. The segment scale explained the
      greatest amount of variation in fish abundance and occurrence, followed by
      segment class, and reach. Segment scale also explained the greatest amount of
      variation in 13 of the 19 analyzed fish assemblage metrics, with segment class
      explaining the greatest amount of variation in the other six fish metrics.
      Segments appear to be a useful spatial scale/unit for measuring and synthesizing
      information for managing rivers and streams. Additionally, segment classes
      provide a useful typology for summarizing the numerous segments into a few
      categories. Reaches are the foundation for the identification of segments and
      segment classes and thus are integral elements of the overall spatial scale
      hierarchy despite reaches not explaining significant variation in fish assemblage
      data.

PMID- 22961586
TI  - Synthesis and selective inhibitory activity against human COX-1 of novel 1-(4
      substituted-thiazol-2-yl)-3,5-di(hetero)aryl-pyrazoline derivatives.
AB  - Novel 1-(4-ethyl carboxylate-thiazol-2-yl)-3,5-di(hetero)aryl-2-pyrazoline
      derivatives were obtained by reacting 3,5-di(hetero)aryl-1-thiocarbamoyl-2
      pyrazolines with the ethyl ester of alpha-bromo-pyruvic acid. The synthesized
      compounds were confirmed by spectroscopic data and assayed to evaluate their in
      vitro ability to inhibit both isoforms of human cyclooxygenase (hCOX). Some
      derivatives (compounds 5, 6, 13, 16, and 17) displayed promising selectivity
      against hCOX-1 in the micromolar range and were shown to have a selectivity index
      similar or better than the reference drugs (indometacin, diclofenac). The
      introduction of a phenyl or a 4-F-phenyl ring on the C5 associated with a 4
      substituted phenyl or a heteroaryl group on the C3 of (4-substituted-thiazol-2
      yl)pyrazoline derivatives improved the activity against hCOX-1. Thanks to these
      preliminary results it could be possible to extend our knowledge of the
      pharmacophoric requirements for the discovery of new pyrazoline-based hCOX-1
      inhibitors.

PMID- 22961587
TI  - The effect of ill health and socioeconomic status on labor force exit and re
      employment: a prospective study with ten years follow-up in the Netherlands.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of ill health and
      socioeconomic status on labor force exit due to unemployment, early retirement,
      disability pension, or becoming economically inactive. A secondary objective was
      to investigate the effect of ill health and socioeconomic status on return to
      work. METHODS: A representative sample of the Dutch working population (N=15 152)
      was selected for a prospective study with ten years follow-up (93 917 person
      years). Perceived health and individual and household characteristics were
      measured at baseline with the Permanent Quality of Life Survey (POLS) during 1999
      2002. Statistics Netherlands ascertained employment status monthly from January
      1999 to December 2008. Cox proportional hazards analyses were used to determine
      the factors that predicted labor force exit and return to work. RESULTS: Ill
      health increased the likelihood of labor force exit into unemployment [hazard
      ratio (HR) 1.89], disability pension (HR 6.39), and early retirement (HR 1.20),
      but was not a determinant of becoming economically inactive (HR 1.07). Workers
      with low socioeconomic status were, even after adjusting for ill health, more
      likely to leave the labor force due to unemployment, disability pension, and
      economic inactivity. Workers with ill health at baseline were less likely to
      return to work after unemployment (HR 0.75) or disability pension (HR 0.62).
      Socioeconomic status did not influence re-employment. CONCLUSIONS: Ill health is
      an important determinant for entering and maintaining paid employment. Workers
      with lower education were at increased risk for health-based selection out of
      paid employment. Policies to improve labor force participation, especially among
      low socioeconomic level workers, should protect workers with health problems
      against exclusion from the labor force.

PMID- 22961588
TI  - Biodegradable polymer-curcumin conjugate micelles enhance the loading and
      delivery of low-potency curcumin.
AB  - PURPOSE: To utilize a novel type of polymer-drug conjugate micelle to enhance the
      delivery of low-potency curcumin. METHODS: Multiple curcumin molecules were
      conjugated to poly(lactic acid) (PLA) via tris(hydroxymethyl)aminomethane (Tris)
      linker producing the hydrophobic drug-binding block; methoxy-poly(ethylene
      glycol) (mPEG) was employed as the hydrophilic block. Micelles were characterized
      by size, loading capacity, stability, and critical micelle concentration (CMC).
      Human hepatocellular carcinoma (HepG2) cells were employed to assess cytotoxicity
      and intracellular targeting ability of micelles. RESULTS: mPEG-PLA-Tris-Cur
      micelles were within nanorange (<100 nm). CMC of such micelles (2.3 +/- 0.4
      MUg/mL) was 10 times lower than mPEG-PLA micelles (27.4 +/- 0.8 MUg/mL). Curcumin
      loading in mPEG-PLA-Tris-Cur micelles reached 18.5 +/- 1.3% (w/w), compared to
      traditional mPEG-PLA micelles at 3.6 +/- 0.4% (w/w). IC(50) of mPEG-PLA-Tris-Cur
      micelles (~22 MUg/mL at curcumin-equivalent dose) was similar to unmodified
      curcumin. Placebo and drug-encapsulated conjugate micelles could be efficiently
      internalized to cytoplasmic compartment of HepG2 cells. CONCLUSIONS: Micelle
      forming polymer-drug conjugates containing multiple drug molecules were an
      efficient means to increase loading and intracellular delivery of low-potency
      curcumin.

PMID- 22961589
TI  - Principal component and clustering analysis on molecular dynamics data of the
      ribosomal L11.23S subdomain.
AB  - With improvements in computer speed and algorithm efficiency, MD simulations are
      sampling larger amounts of molecular and biomolecular conformations. Being able
      to qualitatively and quantitatively sift these conformations into meaningful
      groups is a difficult and important task, especially when considering the
      structure-activity paradigm. Here we present a study that combines two popular
      techniques, principal component (PC) analysis and clustering, for revealing major
      conformational changes that occur in molecular dynamics (MD) simulations.
      Specifically, we explored how clustering different PC subspaces effects the
      resulting clusters versus clustering the complete trajectory data. As a case
      example, we used the trajectory data from an explicitly solvated simulation of a
      bacteria's L11.23S ribosomal subdomain, which is a target of thiopeptide
      antibiotics. Clustering was performed, using K-means and average-linkage
      algorithms, on data involving the first two to the first five PC subspace
      dimensions. For the average-linkage algorithm we found that data-point
      membership, cluster shape, and cluster size depended on the selected PC subspace
      data. In contrast, K-means provided very consistent results regardless of the
      selected subspace. Since we present results on a single model system,
      generalization concerning the clustering of different PC subspaces of other
      molecular systems is currently premature. However, our hope is that this study
      illustrates a) the complexities in selecting the appropriate clustering
      algorithm, b) the complexities in interpreting and validating their results, and
      c) by combining PC analysis with subsequent clustering valuable dynamic and
      conformational information can be obtained.

PMID- 22961590
TI  - Effect of stepwise microhydration on the methylammonium...phenol and
      ammonium...phenol interaction.
AB  - A computational study has been performed for studying the characteristics of the
      interaction of phenol with ammonium and methylammonium cations. The effect of the
      presence of water molecules has also been considered by microhydrating the
      clusters with up to three water molecules. Clusters of phenol with ammonium and
      methylammonium cations present similar characteristics, though ammonium complexes
      have been found to be more stable than the methylammonium ones. The first water
      molecule included in the complexes interacts with a N-H group of ammoniun cations
      and simultaneously with the hydroxyl oxygen atom of phenol (or the aromatic
      ring). This first water molecule is more tightly bound in the complex, so the
      stability gain as more water molecules are included drops significantly by 2-3
      kcal mol(-1) with respect to the first one. As more water molecules are included,
      the differences between favorable coordination sites (the cation, the hydroxyl
      group or a previous water molecule) decrease. As a consequence, several of the
      most stable complexes located including three water molecules already exhibit
      hydrogen bonds between the hydroxyl group and one water molecule. The results
      indicate that a cyclic pattern formed by a series of hydrogen bonds: pi...H-N
      H...O-H...O-phi, is characteristic of the most stable minima, being kept as more
      water molecules are included in the system. Therefore, this pattern can be
      expected to be crucial in ammonium cations...phenol interaction if exposed to the
      solvent to any degree.

PMID- 22961591
TI  - A novel murine model to deplete hepatic stellate cells uncovers their role in
      amplifying liver damage in mice.
AB  - We have developed a novel model for depleting mouse hepatic stellate cells (HSCs)
      that has allowed us to clarify their contributions to hepatic injury and
      fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine
      kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render
      proliferating HSCs susceptible to killing in response to ganciclovir (GCV).
      Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was
      provoked to maximize HSC depletion by combining CCl(4) (centrilobular injury)
      with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation
      (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence
      (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type
      (WT) and Tg mice, GCV induced cell death in ~ 50% of HSCs from Tg, but not WT,
      mice. In TG mice treated with CCl(4) +AA+GCV, there was a significant decrease in
      GFAP and desmin-positive cells, compared to WT mice (~ 65% reduction; P < 0.01),
      which was accompanied by a decrease in the expression of HSC-activation markers
      (alpha smooth muscle actin, beta platelet-derived growth factor receptor, and
      collagen I). Similar results were observed after BDL. Associated with HSC
      depletion in both fibrosis models, there was marked attenuation of fibrosis and
      liver injury, as indicated by Sirius Red/Fast Green, hematoxylin and eosin
      quantification, and serum alanine/aspartate aminotransferase. Hepatic expression
      of interleukin-10 and interferon-gamma was increased after HSC depletion. No
      toxicity of GCV in either WT or Tg mice accounted for the differences in injury.
      CONCLUSION: Activated HSCs significantly amplify the response to liver injury,
      further expanding this cell type's repertoire in orchestrating hepatic injury and
      repair.

PMID- 22961592
TI  - Cloning and genomic nucleotide sequence of the matrix attachment region binding
      protein from the halotolerant alga Dunaliella salina.
AB  - In our previous study, the sequence of a matrix attachment region binding protein
      (MBP) cDNA was cloned from the unicellular green alga Dunaliella salina. However,
      the nucleotide sequence of this gene has not been reported so far. In this paper,
      the nucleotide sequence of MBP was cloned and characterized, and its gene copy
      number was determined. The MBP nucleotide sequence is 5641 bp long, and
      interrupted by 12 introns ranging from 132 to 562 bp. All the introns in the D.
      salina MBP gene have orthodox splice sites, exhibiting GT at the 5' end and AG at
      the 3' end. Southern blot analysis showed that MBP only has one copy in the D.
      salina genome.

PMID- 22961593
TI  - Validation of a task-specific scoring system for a microvascular surgery
      simulation model.
AB  - OBJECTIVE/HYPOTHESIS: Simulation models can help develop procedural skills
      outside the clinical setting while also providing a means for evaluation of
      trainees. Objective Structured Assessment of Technical Skills (OSATS) have been
      developed for several procedures. The purpose of this study was to demonstrate
      the construct validity of an OSATS for microvascular anastomosis performed on a
      simulation model using chicken thigh vessels. STUDY DESIGN: Validation study.
      METHODS: An expert panel constructed a task-specific checklist for an OSATS for
      microvascular anastomosis. Twenty surgical staff and trainees performed a
      microvascular anastomosis of a chicken ischiatic artery. Training level and
      microsurgical experience were assessed by questionnaire. The performances were
      recorded and scored by two experts using the task-specific and global scales of
      the OSATS. RESULTS: Analysis of variance revealed a significant effect of
      training and microvascular experience for both the task-specific score and global
      rating scale score (P < .005). Interrater reliability was 0.7. Experience level
      demonstrated a logarithmic relationship with task time. CONCLUSIONS: The
      microvascular OSATS applied to the chicken thigh simulator model differentiated
      between levels of microvascular experience. It demonstrated construct validity
      and reliability for the assessment of procedural competence using a cost
      effective and easily accessible model.

PMID- 22961594
TI  - Myocardial infarction differentially alters sphingolipid levels in plasma,
      erythrocytes and platelets of the rat.
AB  - Three bioactive sphingolipids, namely sphingosine-1-phosphate (S1P), ceramide
      (CER) and sphingosine (SPH) were shown to be involved in ischemia/reperfusion
      injury of the heart. S1P is a powerful cardioprotectant, CER activates apoptosis
      and SPH in a low dose is cardioprotective whereas in a high dose is cardiotoxic.
      The aim of the present study was to examine effects of experimental myocardial
      infarction on the level of selected sphingolipids in plasma, erythrocytes and
      platelets in the rat. Myocardial infarction was produced in male Wistar rats by
      ligation of the left coronary artery. Blood was taken from the abdominal aorta at
      1, 6 and 24 h after the ligation. Plasma, erythrocytes and platelets were
      isolated and S1P, dihydrosphingosine-1-phosphate (DHS1P), SPH, dihydrosphingosine
      (DHS) and CER were quantified by means of an Agilent 6460 triple quadrupole mass
      spectrometer using positive ion electrospray ionization source with multiple
      reaction monitoring. The infarction reduced the plasma level of S1P, DHS1P, SPH
      and DHS but increased the level of total CER. In erythrocytes, there was a sharp
      elevation in the level of SPH and DHS early after the infarction and a reduction
      after 24 h whereas the level of S1P, DHS1P and total CER gradually increased. In
      platelets, the level of each of the examined compounds profoundly decreased 1 and
      6 h after the infarction and partially normalized in 24 h. The results obtained
      clearly show that experimental heart infarction in rats produces deep changes in
      metabolism of sphingolipids in the plasma, platelets and erythrocytes.

PMID- 22961596
TI  - Influence of planktonic and sessile Listeria monocytogenes on Caenorhabditis
      elegans.
AB  - Listeria monocytogenes is the etiologic agent of listeriosis, a food-borne
      disease affecting humans and a variety of animals. In order to combat this
      pathogen, it is crucial to have an understanding of its natural interplay with
      the environment. For this reason, the free soil nematode Caenorhabditis elegans
      was focused upon because of its shared natural habitat with Listeria and its
      potential as a model organism for Listeria pathogenesis. Previous studies have
      generated some contradictory results on Listeria's ability to kill C. elegans,
      making additional interaction studies such as this more attractive. In our study,
      we carried out a series of killing assays in a systematic manner using different
      Listeria strains under different growth conditions. In addition to studying the
      effects of planktonic cells, we examined the interaction between C. elegans and
      sessile listerial cells. Our findings suggest that, rather than causing infection
      and death, L. monocytogenes may extend the life span of C. elegans. This
      indicates that Listeria is not pathogenic to C. elegans. We also found that C.
      elegans can feed and ingest sessile cells, as well as carry the pathogen in its
      gut, implying that C. elegans could be a vehicle for L. monocytogenes spread in
      the environment.

PMID- 22961595
TI  - Impaired left ventricular function in the presence of preserved ejection in
      chronic hypertensive conscious pigs.
AB  - Systolic function is often evaluated by measuring ejection fraction and its
      preservation is often assimilated with the lack of impairment of systolic left
      ventricular (LV) function. Considering the left ventricle as a muscular pump, we
      explored LV function during chronic hypertension independently of increased
      afterload conditions. Fourteen conscious and chronically instrumented pigs
      received continuous infusion of either angiotensin II (n = 8) or saline (n = 6)
      during 28 days. Hemodynamic recordings were regularly performed in the presence
      and 1 h after stopping angiotensin II infusion to evaluate intrinsic LV function.
      Throughout the protocol, the mean arterial pressure steadily increased by 55 +/-
      4 mmHg in angiotensin II-treated animals. There were no significant changes in
      stroke volume, LV fractional shortening or LV wall thickening, indicating the
      lack of alterations in LV ejection. In contrast, we observed maladaptive changes
      with (1) the lack of reduction in isovolumic contraction and relaxation durations
      with heart rate increases, (2) abnormally blunted isovolumic contraction and
      relaxation responses to dobutamine and (3) a linear correlation between
      isovolumic contraction and relaxation durations. None of these changes were
      observed in saline-infused animals. In conclusion, we provide evidence of
      impaired LV function with concomitant isovolumic contraction and relaxation
      abnormalities during chronic hypertension while ejection remains preserved and no
      sign of heart failure is present. The evaluation under unloaded conditions shows
      intrinsic LV abnormalities.

PMID- 22961598
TI  - Natural variants in the major neutralizing epitope of human papillomavirus minor
      capsid protein L2.
AB  - The amino terminus of the human papillomavirus minor capsid protein L2 contains a
      major cross-neutralizing epitope that provides the basis for the development of a
      broadly protective HPV vaccine. This attainable broad protection would eliminate
      one of the major drawbacks of the commercial L1-based prophylactic vaccines. In
      this study, we asked whether there are natural variants of the L2 cross
      neutralizing epitope and if these variants provide means for immune escape from
      vaccine-induced anti-L2 antibodies. For this, we isolated in silico and in vitro,
      a total of 477 L2 sequences of HPV types 16, 18, 31, 45, 51, 52 and 58. We
      identified natural L2 epitope variants for HPV 18, 31, 45 and 51. To determine
      whether these variants escape L2-directed neutralization, we generated
      pseudovirions encompassing the natural variants and tested these in an in vitro
      neutralization assay using monoclonal and polyclonal antibodies. Our results
      indicate that natural variants of the L2 major neutralizing epitope are frequent
      among two different study populations from Germany and Mongolia and in the
      GenBank database. Of two identified HPV 31 L2 single amino acid variants, one
      could be neutralized well, while the other variant was neutralized very poorly.
      We also observed that single amino acid variants of HPV 18 and 45 are neutralized
      well while a HPV 18 double variant was neutralized at significantly lower rates,
      indicating that L2 variants have to be accounted for when developing HPV L2-based
      prophylactic vaccines.

PMID- 22961599
TI  - Association between pain catastrophizing, spouse responses to pain, and blood
      pressure in chronic pain patients: a pathway to potential comorbidity.
AB  - BACKGROUND: Chronic pain has been shown to be highly comorbid with other medical
      conditions. Theoretical and empirical associations between pain and
      cardiovascular health can be made based on the current literature. Psychosocial
      variables associated with the pain experience may, however, have an impact on
      cardiovascular health. PURPOSE: The purpose of this study was to examine how
      cognitive and interpersonal aspects of chronic pain, including pain
      catastrophizing (PC) and negative spouse responses (NSR), relate to systolic and
      diastolic blood pressure (SBP, DBP) as cardiovascular risk factors. METHODS: Data
      were collected from 57 treatment-seeking patients with chronic musculoskeletal
      pain. Participants completed the West Haven-Yale Multidimensional Pain Inventory,
      Pain Catastrophizing Scale, and pain severity ratings based on an analog pain
      scale. In addition, participants consented to a medical chart review to collect
      blood pressure and prescribed medication data. Hierarchical linear regressions
      were used to test associations between PC and NSR, and blood pressure while
      controlling cardiac medication status. RESULTS: A positive association between PC
      and both SBP and DBP was found. A positive association was also found for NSR and
      SBP. These findings suggest that psychosocial aspects of chronic pain may
      represent a direct risk for elevated blood pressure and, thus, increased risk for
      cardiovascular health problems. CONCLUSIONS: Psychosocial aspects of pain may
      constitute a form of chronic stress as described in the cardiovascular reactivity
      literature. The findings highlight the need for comprehensive multidimensional
      treatments of pain.

PMID- 22961600
TI  - Subdivision of molecularly-classified groups by new gene signatures in breast
      cancer patients.
AB  - Gene expression patterns as well as gene interactions are under investigation for
      their involvement in tumour heterogeneity. The molecular classification of breast
      cancer based on hormone receptor expression, grade and HER2 receptor levels, is
      indicative but not adequate enough to complete the prognostic data. The
      objectives of this study were to validate the prognostic value of 19 genes,
      solely, and as parts of classifiers (sets of genes), in breast cancer patients
      and to determine whether the expression of these genes and classifiers is
      correlated with breast cancer molecular classification. Gene expression was
      examined in the blood of 88 breast cancer patients and 50 healthy controls using
      multiplex quantitative real-time PCR. Patients with a second primary malignancy
      showed a statistically significant difference when compared with: i) patients
      with a single breast cancer, for an 8-gene classifier (p<0.02); and ii) healthy
      individuals (classifier FBX033, FLJ339115) (p<0.01), with respect to gene
      expression. The classifier ENY2, USP38 was associated with the development of
      primary breast cancer. A newly established classifier (ENY2, USP38, RPS7, Osbpl-1
      and ETF1) indicated a statistically significant association with HER2 subtype
      patients, compared to patients with a different molecular classification
      (p<0.04). The gene FLJ33915 was differentially expressed in a subgroup of HER2
      positive patients with infiltrated axillary lymph nodes (p<0.028). We validated
      the prognostic value of 4 classifiers for primary and second primary malignancy.
      Evidence of a classifier predicting the HER2 subtype and the gene FLJ33915 which
      subdivides HER2 subtype patients is also presented.

PMID- 22961601
TI  - A systems-level approach to human epileptic seizures.
AB  - Epileptic seizures are due to the pathological collective activity of large
      cellular assemblies. A better understanding of this collective activity is
      integral to the development of novel diagnostic and therapeutic procedures. In
      contrast to reductionist analyses, which focus solely on small-scale
      characteristics of ictogenesis, here we follow a systems-level approach, which
      combines both small-scale and larger-scale analyses. Peri-ictal dynamics of
      epileptic networks are assessed by studying correlation within and between
      different spatial scales of intracranial electroencephalographic recordings
      (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant
      epilepsy. Epileptiform activity as recorded by a single iEEG electrode is
      determined objectively by the signal derivative and then subjected to a
      multivariate analysis of correlation between all iEEG channels. We find that
      during seizure, synchrony increases on the smallest and largest spatial scales
      probed by iEEG. In addition, a dynamic reorganization of spatial correlation is
      observed on intermediate scales, which persists after seizure termination. It is
      proposed that this reorganization may indicate a balancing mechanism that
      decreases high local correlation. Our findings are consistent with the hypothesis
      that during epileptic seizures hypercorrelated and therefore functionally
      segregated brain areas are re-integrated into more collective brain dynamics. In
      addition, except for a special sub-group, a highly significant association is
      found between the location of ictal iEEG activity and the location of areas of
      relative decrease of localised EEG correlation. The latter could serve as a
      clinically important quantitative marker of the seizure onset zone (SOZ).

PMID- 22961602
TI  - Physical training prevents oxidative stress in L-NAME-induced hypertension rats.
AB  - The present study investigated the effects of a 6-week swimming training on blood
      pressure, nitric oxide (NO) levels and oxidative stress parameters such as
      protein and lipid oxidation, antioxidant enzyme activity and endogenous non
      enzymatic antioxidant content in kidney and circulating fluids, as well as on
      serum biochemical parameters (cholesterol, triglycerides, urea and creatinine)
      from Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced
      hypertension treated rats. Animals were divided into four groups (n = 10):
      Control, Exercise, L-NAME and Exercise L-NAME. Results showed that exercise
      prevented a decrease in NO levels in hypertensive rats (P < 0.05). An increase in
      protein and lipid oxidation observed in the L-NAME-treated group was reverted by
      physical training in serum from the Exercise L-NAME group (P < 0.05). A decrease
      in the catalase (CAT) and superoxide dismutase (SOD) activities in the L-NAME
      group was observed when compared with normotensive groups (P < 0.05). In kidney,
      exercise significantly augmented the CAT and SOD activities in the Exercise L
      NAME group when compared with the L-NAME group (P < 0.05). There was a decrease
      in the non-protein thiols (NPSH) levels in the L-NAME-treated group when compared
      with the normotensive groups (P < 0.05). In the Exercise L-NAME group, there was
      an increase in NPSH levels when compared with the L-NAME group (P < 0.05). The
      elevation in serum cholesterol, triglycerides, urea and creatinine levels
      observed in the L-NAME group were reverted to levels close to normal by exercise
      in the Exercise L-NAME group (P < 0.05). Exercise training had hypotensive
      effect, reducing blood pressure in the Exercise L-NAME group (P < 0.05). These
      findings suggest that physical training could have a protector effect against
      oxidative damage and renal injury caused by hypertension.

PMID- 22961603
TI  - Screening of promising chemotherapeutic candidates from plants against human
      adult T-cell leukemia/lymphoma (II): apoptosis of antiproliferactive principle
      (24,25-dihydrowithanolide D) against ATL cell lines and structure-activity
      relationships with withanolides isolated from solanaceous plants.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an incurable peripheral T-cell malignancy
      caused by human T-cell lymphotropic virus type I. In our preceding paper, 214
      extracts from 162 plants were screened to elucidate the antiproliferative
      principles against ATL cell lines. Several withanolides were isolated and the
      structure-activity relationships (SAR) examined. To extend the search for SAR, 31
      further withanolides, previously isolated from solanaceous plants, were tested
      against ATL cell lines. The presence of a 4beta-hydroxy group as well as a
      5beta,6beta-epoxy group appeared to be essential for the activity. In contrast,
      the presence of a sugar moiety at either the 3- or the 27-position led to a
      reduction in the activity. Furthermore, 24,25-dihydrowithanolide D (13) was
      identified as the most potent inhibitor, showing selective toxicity against ATL
      cell lines by inducing apoptotic cell death.

PMID- 22961604
TI  - Adapting school-based substance use prevention curriculum through cultural
      grounding: a review and exemplar of adaptation processes for rural schools.
AB  - A central challenge facing twenty-first century community-based researchers and
      prevention scientists is curriculum adaptation processes. While early prevention
      efforts sought to develop effective programs, taking programs to scale implies
      that they will be adapted, especially as programs are implemented with
      populations other than those with whom they were developed or tested. The
      principle of cultural grounding, which argues that health message adaptation
      should be informed by knowledge of the target population and by cultural
      insiders, provides a theoretical rational for cultural regrounding and presents
      an illustrative case of methods used to reground the keepin' it REAL substance
      use prevention curriculum for a rural adolescent population. We argue that
      adaptation processes like those presented should be incorporated into the design
      and dissemination of prevention interventions.

PMID- 22961606
TI  - Effect of acupuncture treatment for weight loss on gut flora in patients with
      simple obesity.

PMID- 22961605
TI  - The combined effect of acupuncture and Tanacetum parthenium on quality of life in
      women with headache: randomised study.
AB  - BACKGROUND: The aim of the present study was to investigate the efficacy and
      tolerability of acupuncture (AC), Tanacetum (TAN) or combined treatment on
      quality of life in women with chronic migraine (CM). METHODS: A total of 69 women
      volunteers were randomly divided into 3 groups: AC, acupuncture administered in
      20 sessions over 10 weeks (n=22); TAN, at 150 mg/day (n=23); and AC+TAN (n=23).
      The primary outcome was Short-Form 36 (SF-36) quality of life assessment score.
      Secondary outcomes included the Migraine Disability Assessment (MIDAS) and visual
      analogue scale (VAS) score experienced after randomisation. RESULTS: AC+TAN was
      statistically significantly more effective than AC or TAN alone in overall health
      related quality of life (SF-36; p<0.05), on MIDAS score (-35.1 (10.6) AC vs -24.8
      (11.7) TAN vs -42.5 (9.8) AC+TAN; p<0.05) and in reducing the mean score of pain
      on VAS (-5.6 (2.4) AC vs -3.7 (2.1) TAN vs -6.4 (3.1) AC+TAN; p<0.05).
      CONCLUSIONS: The present work shows an improvement of the quality of life and
      better analgesic effect of acupuncture combined with TAN treatment on migraine
      pain in women when compared with acupuncture or TAN alone.

PMID- 22961607
TI  - Large-scale femtoliter droplet array for digital counting of single biomolecules.
AB  - We present a novel device employing one million femtoliter droplets immobilized
      on a substrate for the quantitative detection of extremely low concentrations of
      biomolecules in a sample. Surface-modified polystyrene beads carrying either zero
      or a single biomolecule-reporter enzyme complex are efficiently isolated into
      femtoliter droplets formed on hydrophilic-in-hydrophobic surfaces. Using a
      conventional micropipette, this is achieved by sequential injection first with an
      aqueous solution containing beads, and then with fluorinated oil. The
      concentration of target biomolecules is estimated from the ratio of the number of
      signal-emitting droplets to the total number of trapped beads (digital counting).
      The performance of our digital counting device was demonstrated by detecting a
      streptavidin-beta-galactosidase conjugate with a limit of detection (LOD) of 10
      zM. The sensitivity of our device was >20-fold higher than that noted in previous
      studies where a smaller number of reactors (fifty thousand reactors) were used.
      Such a low LOD was achieved because of the large number of droplets in an array,
      allowing simultaneous examination of a large number of beads. When combined with
      bead-based enzyme-linked immunosorbent assay (digital ELISA), the LOD for the
      detection of prostate specific antigen reached 2 aM. This value, again, was
      improved over that noted in a previous study, because of the decreased
      coefficient of variance of the background measurement determined by the Poisson
      noise. Our digital counting device using one million droplets has great potential
      as a highly sensitive, portable immunoassay device that could be used to diagnose
      diseases.

PMID- 22961608
TI  - Identification of risks associated with the prescribing and dispensing of oral
      anticancer medicines in Ireland.
AB  - BACKGROUND: Oral anticancer medicines (OAM) facilitate transfer of cancer care
      into the community, where safeguards developed in hospitals that control their
      prescribing, dispensing and administration may not exist. OBJECTIVE: To determine
      if the systems of prescribing and dispensing OAM in Ireland facilitate clinical
      verification of the prescription, thereby ensuring treatment is tailored and
      appropriate for the patient. SETTING: Randomly selected community pharmacies in
      Ireland and all Irish hospitals with cancer services. METHOD: A questionnaire was
      sent to a random selection of Irish community pharmacists. A different
      questionnaire was sent to all Irish hospitals treating cancer patients. One
      hundred OAM prescriptions were retrospectively reviewed, to assess the
      information presented and the potential barriers to a community pharmacist
      performing a clinical verification of the prescription. MAIN OUTCOME MEASURE:
      Community pharmacist survey: problems experienced when dispensing OAM and risk
      factors identified with the current system. Hospital pharmacist survey:
      proportion of hospitals that clinically verify prescriptions for parenteral
      versus oral anticancer medicines and associated policies. OAM prescription
      review: proportion of OAM prescriptions that contained sufficient information for
      a community pharmacist to clinically verify the prescription and safely dispense
      the medication. RESULTS: Sixty-four percent of community pharmacist respondents
      felt they did not have enough information available to them to safely dispense
      these prescriptions, and 74 % felt that patients are at risk with the current
      Irish system of prescribing and dispensing OAM. Irish hospitals do not have
      systems to ensure that all OAM prescriptions are clinically verified by a
      pharmacist. Seventeen different agents were prescribed on the prescriptions
      reviewed. The information provided to the community pharmacist would have allowed
      them to clinically verify 7 % of the OAM prescriptions. CONCLUSION: Prescriptions
      for OAM reach the community pharmacist with little chance that they have been
      clinically verified in the hospital and the medicine reaches the patient with
      little chance that the community pharmacist has been able to clinically verify
      it. Healthcare risks are increased when inadequate information about patients and
      their medicines are available. Appropriate specialist practitioners should be
      provided nationally to clinically oversee each stage of the OAM use process.

PMID- 22961609
TI  - Detection of retinal lesions in diabetic retinopathy: comparative evaluation of 7
      field digital color photography versus red-free photography.
AB  - Red-free light allows better detection of vascular lesions as this wavelength is
      absorbed by hemoglobin; however, the current gold standard for the detection and
      grading of diabetic retinopathy remains 7-field color fundus photography. The
      goal of this study was to compare the ability of 7-field fundus photography using
      red-free light to detect retinopathy lesions with corresponding images captured
      using standard 7-field color photography. Non-stereoscopic standard 7-field 30
      degrees  digital color fundus photography and 7-field 30 degrees  digital red
      free fundus photography were performed in 200 eyes of 103 patients with various
      grades of diabetic retinopathy ranging from mild to moderate non-proliferative
      diabetic retinopathy to proliferative diabetic retinopathy. The color images (n =
      1,400) were studied with corresponding red-free images (n = 1,400) by one retina
      consultant (PV) and two senior residents training in retina. The various retinal
      lesions [microaneurysms, hemorrhages, hard exudates, soft exudates, intra-retinal
      microvascular anomalies (IRMA), neovascularization of the retina elsewhere (NVE),
      and neovascularization of the disc (NVD)] detected by all three observers in each
      of the photographs were noted followed by determination of agreement scores using
      kappa values (range 0-1). Kappa coefficient was categorized as poor (<=0), slight
      (0.01-0.20), fair (0.2 -0.40), moderate (0.41-0.60), substantial (0.61-0.80), and
      almost perfect (0.81-1). The number of lesions detected by red-free images alone
      was higher for all observers and all abnormalities except hard exudates.
      Detection of IRMA was especially higher for all observers with red-free images.
      Between image pairs, there was substantial agreement for detection of hard
      exudates (average kappa = 0.62, range 0.60-0.65) and moderate agreement for
      detection of hemorrhages (average kappa = 0.52, range 0.45-0.58), soft exudates
      (average kappa = 0.51, range 0.42-0.61), NVE (average kappa = 0.47, range 0.39
      0.53), and NVD (average kappa = 0.51, range 0.45-0.54). Fair agreement was noted
      for detection of microaneurysms (average kappa = 0.29, range 0.20-0.39) and IRMA
      (average kappa = 0.23, range 0.23-0.24). Inter-observer agreement with color
      images was substantial for hemorrhages (average kappa = 0.72), soft exudates
      (average kappa = 0.65), and NVD (average kappa = 0.65); moderate for
      microaneurysms (average kappa = 0.42), NVE (average kappa = 0.44), and hard
      exudates (average kappa = 0.59) and fair for IRMA (average kappa = 0.21). Inter
      observer agreement with red-free images was substantial for hard exudates
      (average kappa = 0.63) and moderate for detection of hemorrhages (average kappa =
      0.56), SE (average kappa = 0.60), IRMA (average kappa = 0.50), NVE (average kappa
      = 0.44), and NVD (average kappa = 0.45). Digital red-free photography has a
      higher level of detection ability for all retinal lesions of diabetic
      retinopathy. More advanced grades of retinopathy are likely to be detected
      earlier with red-free imaging because of its better ability to detect IRMA, NVE,
      and NVD. Red-free monochromatic imaging of the retina is a more effective and
      less costly alternative for detection of vision-threatening diabetic retinopathy.

PMID- 22961610
TI  - Use of clinically based troponin underestimates the cardiac injury in non-cardiac
      surgery: a single-centre cohort study in 51,701 consecutive patients.
AB  - PURPOSE: Postoperative myocardial infarction causes hundreds of thousands of
      deaths annually, and "failure to rescue" is a leading cause of hospital
      mortality. Strategies to recognize cardiac injury are important to reduce the
      burden of cardiac-related morbidity. For these reasons, we chose to assess the
      association between postoperative troponin I elevations and 30-day in-hospital
      mortality and, secondarily, to compare the predictive value of regularly
      scheduled troponin estimates with troponin ordered in response to clinical
      indications. METHODS: We carried out a retrospective cohort analysis of 51,701
      consecutive patients throughout 2003 to 2009. All patients were from a single
      university referral hospital and included all non-cardiac non-transplant surgery
      patients requiring overnight admission. Logistic regression was used to assess
      the risk-adjusted associations between troponin I and 30-day in-hospital
      mortality. RESULTS: The multivariable predictive model for death improved after
      troponin I was included. The receiver operating characteristic was 0.902 before
      troponin I vs 0.934 after troponin I (P<0.0001). The likelihood ratio for
      troponin was 3.0 (95% confidence interval 2.8 to 3.2) and evident in each
      surgical service. Increasing troponin I showed a dose-response associated with
      increased mortality, and compared with clinically based measurements, a regularly
      scheduled postoperative troponin protocol showed a threefold increase in the
      probability of detecting myocardial injury. However, troponin I was not found to
      improve the risk prediction model in the lowest risk patients (n=18,953;
      probability of death<0.02%) with one cardiac death. CONCLUSIONS: Postoperatively
      elevated troponin I is associated with 30-day in-hospital mortality in a dose
      dependent manner. A postoperative measurement protocol provides a threefold
      increase in the ability to detect myocardial injury. Conversely, in patients with
      a low mortality risk, cardiac injury is low; there is minimal improvement in the
      ability to detect cardiac injury, and the rescue rates from cardiac injury are
      excellent. These findings suggest that a surveillance protocol of troponin I
      would be optimal when limited to moderate to high-risk patients.

PMID- 22961611
TI  - Prognosis of primary central nervous system lymphoma treated with radiotherapy
      alone.
AB  - PURPOSE: Standard treatment for patients with primary central nervous system
      (CNS) lymphoma involves combining high-dose methotrexate-based chemotherapy and
      radiation. However, chemotherapy is sometimes contraindicated, and radiotherapy
      alone becomes the only option. We retrospectively investigated the clinical
      outcomes of primary CNS lymphoma patients treated with radiotherapy alone.
      MATERIALS AND METHODS: Between 1983 and 2006, 35 patients (median age 69 years,
      range 37-89 years) with primary CNS lymphoma were treated with radiotherapy
      alone. Of these, 74 % had an Eastern Cooperative Oncology Group performance
      status (PS) of 2-4. Most patients (91 %) received whole-brain irradiation with or
      without irradiation boost to the tumor site (median dose 50 Gy, range 22-50 Gy);
      remaining patients received partial brain irradiation. RESULTS: Median follow-up
      time was 20 (range 1-152) months, median survival time was 20 months, and the 1-
      and 2-year overall survival rates were 65 and 32 %, respectively. Median survival
      in patients aged <70 and >= 70 years was 26 and 10 months, respectively (p =
      0.01). CONCLUSION: Median survival with radiotherapy alone was 20 months.
      Patients aged <70 years have a better prognosis than those >= 70 years.

PMID- 22961612
TI  - Effects of land use changes on the ecosystem service values of a reclamation farm
      in northeast China.
AB  - Intensive agricultural development can change land use, which can further affect
      regional ecosystem services and functions. With the rapid growth of the
      population and the national demand for food, the northeast of China, which is
      located in the high latitudes, has experienced four agricultural developments
      since the 1950s. The original wetlands of this area were developed for farmland.
      The evaluation of ecosystem services is conducted to reveal the ecosystem status
      and variable trends caused by land reclamation. The aim of this study is to
      provide scientific basis for environmental management and for the sustainable
      development of agriculture in Northeast China. With GIS-RS technology, a typical
      farm was chosen to analyze variations in the ecosystem service value in response
      to land use changes during the study period. The total ecosystem service value of
      the farm decreased from 7523.10 million Yuan in 1979 to 4023.59 million Yuan in
      2009 with an annual rate of -1.6 % due to the decreasing areas of woodland and
      wetland. The increased areas of cropland, water area and grassland partly offset
      the loss of the total value, but the loss was still greater than the
      compensation. Waste treatment and climate regulation were the top two service
      functions with high service values, contributing to approximately 50 % of the
      total service value. The spatial difference of the ecosystem service value also
      was analyzed. The wetlands located in the central and northeastern sections of
      the farm changed significantly. From the aspect of ecosystem service value, the
      wetland and water area should be conserved, as they have the highest value
      coefficients. The accuracy of the value coefficient, however, needs to be studied
      further in future research.

PMID- 22961613
TI  - Significance of perceived social expectation and implications to conservation
      education: turtle conservation as a case study.
AB  - The likelihood of participating in wildlife conservation programs is dependent on
      social influences and circumstances. This view is validated by a case study of
      behavioral intention to support conservation of Asian turtles. A total of 776
      college students in China completed a questionnaire survey designed to identify
      factors associated with their intention to support conservation. A regression
      model explained 48 % of variance in the level of intention. Perceived social
      expectation was the strongest predictor, followed by attitudes toward turtle
      protection and perceived behavioral control, altogether explaining 44 %. Strong
      ethics and socio-economic variables had some statistical significant impacts and
      accounted for 3 % of the variance. The effects of general environmental
      awareness, trust and responsibility ascription were modest. Knowledge about
      turtles was a weak predictor. We conclude that perceived social expectation is a
      limiting factor of conservation behavior. Sustained interest and commitment to
      conservation can be created by enhancing positive social influences. Conservation
      educators should explore the potential of professionally supported, group-based
      actions that can nurture a sense of collective achievement as part of an
      educational campaign.

PMID- 22961614
TI  - Mixed-grass prairie canopy structure and spectral reflectance vary with
      topographic position.
AB  - Managers of the nearly 0.5 million ha of public lands in North and South Dakota,
      USA rely heavily on manual measurements of canopy height in autumn to ensure
      conservation of grassland structure for wildlife and forage for livestock.
      However, more comprehensive assessment of vegetation structure could be achieved
      for mixed-grass prairie by integrating field survey, topographic position
      (summit, mid and toeslope) and spectral reflectance data. Thus, we examined the
      variation of mixed-grass prairie structural attributes (canopy leaf area,
      standing crop mass, canopy height, nitrogen, and water content) and spectral
      vegetation indices (VIs) with variation in topographic position at the Grand
      River National Grassland (GRNG), South Dakota. We conducted the study on a 36,000
      ha herbaceous area within the GRNG, where randomly selected plots (1 km(2) in
      size) were geolocated and included summit, mid and toeslope positions. We tested
      for effects of topographic position on measured vegetation attributes and VIs
      calculated from Landsat TM and Advanced Spaceborne Thermal Emission and
      Reflection Radiometer (ASTER) data collected in July 2010. Leaf area, standing
      crop mass, canopy height, nitrogen, and water content were lower at summits than
      at toeslopes. The simple ratio of Landsat Band 7/Band 1 (SR71) was the VI most
      highly correlated with canopy standing crop and height at plot and landscape
      scales. Results suggest field and remote sensing-based grassland assessment
      techniques could more comprehensively target low structure areas at minimal
      expense by layering modeled imagery over a landscape stratified into topographic
      position groups.

PMID- 22961615
TI  - Invasive knotweeds are highly tolerant to salt stress.
AB  - Japanese knotweed s.l. are some of the most invasive plants in the world. Some
      genotypes are known to be tolerant to the saline concentrations found in salt
      marshes. Here we focus on tolerance to higher concentrations in order to assess
      whether the species are able to colonize and establish in highly stressful
      environments, or whether salt is an efficient management tool. In a first
      experiment, adult plants of Fallopia japonica, Fallopia * bohemica and Fallopia
      sachalinensis were grown under salt stress conditions by watering with saline
      concentrations of 6, 30, 120, or 300 g L(-1) for three weeks to assess the
      response of the plants to a spill of salt. At the two highest concentrations,
      their leaves withered and fell. There were no effects on the aboveground parts at
      the lowest concentrations. Belowground dry weight and number of buds were reduced
      from 30 and 120 g L(-1) of salt, respectively. In a second experiment, a single
      spraying of 120 g L(-1) of salt was applied to individuals of F. * bohemica and
      their stems were clipped to assess the response to a potential control method. 60
      % of the plants regenerated. Regeneration was delayed by the salt treatment and
      shoot growth slowed down. This study establishes the tolerance of three Fallopia
      taxa to strong salt stress, with no obvious differences between taxa. Their salt
      tolerance could be an advantage in their ability to colonize polluted
      environments and to survive to spills of salt.

PMID- 22961616
TI  - Flash flood occurrences since the 17th century in steep drainage basins in
      southern Italy.
AB  - The historical floods that have occurred since the seventeenth century were
      collected for a study area in southern Italy. Damages caused by floods, rainfall
      and the main anthropogenic modifications are discussed all together. The aim was
      to assess whether the frequency of floods is changing and, if so, whether these
      changes can be attributed to either rainfall and/or anthropogenic modifications.
      In 4 % of cases, mainly occurred in past centuries, floods damaged people.
      Hydraulic works, roads and private buildings were the more frequently damaged
      elements (25, 18 and 14 % of the cases, respectively). The annual variability of
      rainfall was discussed using an annual index. Short duration-high intensity
      rainfalls were characterized considering time series of annual maxima of 1, 3, 6,
      12, and 24 h and daily rainfall. The rainfall shows a decreasing trend, in terms
      of both the annual maximum of short duration and the annual amount. The
      population has been progressively increasing since the sixteenth century, except
      during the years following the catastrophic 1908 earthquake. The rate of
      population growth has been very high since the second half of the twentieth
      century; the urbanized areas greatly increased, especially following the second
      half of the twentieth century. At the same time, the trend of damaging floods has
      been increasing, especially since the seventies. The analysis indicates that,
      despite a rainfall trend favourable towards a reduction in flood occurrence,
      floods damage has not decreased. This seems to be mainly the effect of
      mismanagement of land use modifications.

PMID- 22961617
TI  - Epilithic community metabolism as an indicator of impact and recovery in streams
      affected by acid mine drainage.
AB  - We measured biomass and metabolism of epilithic communities on five dates in
      different seasons at four sites in a watershed that has received extensive
      restoration for acid mine drainage (AMD) through the construction of passive
      treatment systems. Chlorophyll a biomass and productivity directly corresponded
      to AMD stress from coal mining. The site downstream of extensive passive
      treatment had significantly greater biomass and gross primary productivity rates
      than the site receiving only untreated AMD, but values were below those for two
      reference sites, indicating incomplete recovery. The degree of difference in
      these metrics among sites varied seasonally, primarily related to differences in
      canopy cover changes, but the ranking of sites in terms of stress generally was
      consistent. Reference sites had a significantly greater chlorophyll a/pheophytin
      ratio than untreated and treated sites, also indicating AMD stressed the
      communities. Community respiration was less affected by AMD stress than
      productivity or chlorophyll a. Productivity measures are not widely used to
      assess AMD impacts, and have been shown to both increase and decrease with AMD
      stress. The elimination of herbivores in AMD-impacted streams can increase
      productivity in the benthic algal community. Our study found productivity
      decreased with increasing AMD stress. Although sites with AMD stress had reduced
      herbivore populations, light, nutrients and metal precipitates appear to have
      limited growth of AMD-tolerant algal taxa. Therefore, it appears changes in food
      web structure due to AMD stress had less of an effect on epilithic productivity
      than environmental conditions within the stream.

PMID- 22961618
TI  - The harvest and management of migratory bird eggs by Inuit in Nunatsiavut,
      Labrador.
AB  - This paper presents the results of collaborative research conducted in 2007 on
      the harvest of migratory bird eggs by Inuit households of Nunatsiavut, Labrador.
      Harvest variability between communities and species is examined, as is the social
      and ecological factors affecting the 2007 Inuit egg harvest. Representing the
      first comprehensive account of Inuit egg use in Labrador, this information should
      be valuable to agencies responsible for managing migratory bird populations in
      North America and will contribute to a more informed understanding of the
      complexity and temporal variability in subsistence harvesting among Labrador
      Inuit. It is argued that the recognition of this complexity will be critical as
      the Nunatsiavut Government and other wildlife management agencies formulate
      management policies that are supportive rather, than constraining, to Inuit
      resource use in the future.

PMID- 22961619
TI  - Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around
      functional synapses in Alzheimer's disease.
AB  - Perineuronal matrix is an extracellular protein scaffold to shape neuronal
      responsiveness and survival. Whilst perineuronal nets engulf the somatodendritic
      axis of neurons, axonal coats are focal extracellular protein aggregates
      surrounding individual synapses. Here, we addressed the chemical identity and
      subcellular localization of both perineuronal and perisynaptic matrices in the
      human hippocampus, whose neuronal circuitry is progressively compromised in
      Alzheimer's disease. We hypothesized that (1) the cellular expression sites of
      chondroitin sulphate proteoglycan-containing extracellular matrix associate with
      specific neuronal identities, reflecting network dynamics, and (2) the regional
      distribution and molecular composition of axonal coats must withstand Alzheimer's
      disease-related modifications to protect functional synapses. We show by epitope
      specific antibodies that the perineuronal protomap of the human hippocampus is
      distinct from other mammals since pyramidal cells but not calretinin(+) and
      calbindin(+) interneurons, neurochemically classified as novel neuronal subtypes,
      lack perineuronal nets. We find that cartilage link protein-1 and brevican
      containing matrices form isolated perisynaptic coats, engulfing both inhibitory
      and excitatory terminals in the dentate gyrus and entorhinal cortex.
      Ultrastructural analysis revealed that presynaptic neurons contribute components
      of perisynaptic coats via axonal transport. We demonstrate, by combining
      biochemical profiling and neuroanatomy in Alzheimer's patients and transgenic
      (APdE9) mice, the preserved turnover and distribution of axonal coats around
      functional synapses along dendrite segments containing hyperphosphorylated tau
      and in amyloid-beta-laden hippocampal microdomains. We conclude that the
      presynapse-driven formation of axonal coats is a candidate mechanism to maintain
      synapse integrity under neurodegenerative conditions.

PMID- 22961621
TI  - Coarse-grained simulations for organic molecular liquids based on Gay-Berne and
      electric multipole potentials.
AB  - Coarse-grained studies of CH(3)SH, CH(3)CHO and CHCl(3) liquids, based on
      anisotropic Gay-Berne (GB) and electric multipole potentials (EMP), demonstrate
      that the coarse-grained model is able to qualitatively reproduce the results
      obtained from the atomistic model (AMOEBA polarizable force field) and allows for
      significant saving in computation time. It should be pointed out that the
      accuracy of the coarse-grained model is very sensitive to how well the
      anisotropic GB particle is defined and how satisfactorily the EMP sites are
      chosen.

PMID- 22961620
TI  - Overexpression of human wild-type FUS causes progressive motor neuron
      degeneration in an age- and dose-dependent fashion.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)
      are relentlessly progressive neurodegenerative disorders with overlapping
      clinical, genetic and pathological features. Cytoplasmic inclusions of fused in
      sarcoma (FUS) are the hallmark of several forms of FTLD and ALS patients with
      mutations in the FUS gene. FUS is a multifunctional, predominantly nuclear, DNA
      and RNA binding protein. Here, we report that transgenic mice overexpressing wild
      type human FUS develop an aggressive phenotype with an early onset tremor
      followed by progressive hind limb paralysis and death by 12 weeks in homozygous
      animals. Large motor neurons were lost from the spinal cord accompanied by
      neurophysiological evidence of denervation and focal muscle atrophy. Surviving
      motor neurons in the spinal cord had greatly increased cytoplasmic expression of
      FUS, with globular and skein-like FUS-positive and ubiquitin-negative inclusions
      associated with astroglial and microglial reactivity. Cytoplasmic FUS inclusions
      were also detected in the brain of transgenic mice without apparent neuronal loss
      and little astroglial or microglial activation. Hemizygous FUS overexpressing
      mice showed no evidence of a motor phenotype or pathology. These findings
      recapitulate several pathological features seen in human ALS and FTLD patients,
      and suggest that overexpression of wild-type FUS in vulnerable neurons may be one
      of the root causes of disease. Furthermore, these mice will provide a new model
      to study disease mechanism, and test therapies.

PMID- 22961622
TI  - Design of molecular switching and signaling based on proton transfer in 2-hydroxy
      Schiff bases: a computational study.
AB  - The present work aims to exploit the possibility of using the tautomerism in 2
      hydroxy Schiff bases for molecular switching. The enol imine (E)<=> enaminone (K)
      tautomerization in a series of 2-hydroxy Schiff bases have been investigated
      theoretically at the DFT/B3LYP/6-311G** level of theory. The intramolecular
      proton transfer processes have been explored, transition structures have been
      located and characterized. The kinetics and thermodynamics of the proton transfer
      process, and its time scale have been computed and discussed in the framework of
      the suitability as molecular switches. Substituent effects have been computed and
      its effect on the enthalpy changes (?H*) and activation energies (?G*) have been
      analyzed and discussed. Nonspecific solvent effects have also been taken into
      account by using the polarized continuum model (IPCM) of two different solvent.
      The tautomerization energies are decreased and hence the endothermic nature of
      the enol imine <=> enaminone tautomerization. The potential energy barriers, on
      the other hand, are increased due to the relative destabilization of the
      transition states. The NBO charge populations show that there is a high positive
      charge on the hydrogen atom during the process in all cases, which confirms that
      the proton transfer proceeds through a three-center interaction. The proton
      transfer processes, in all cases studied are kinetically allowed. The low
      potential energy barrier suggests that interconversion between the two tautomeric
      forms is spontaneous and the two forms may coexist.

PMID- 22961623
TI  - Looking for high energy density compounds among polynitraminecubanes.
AB  - Based on fully optimized geometric structures at DFT-B3LYP/6-311G** level, we
      calculated electronic structures, heats of formation, strain energies, bond
      dissociation energies and detonation performance (detonation velocity and
      detonation pressure) for a series of polynitraminecubanes. Our results have shown
      that energy gaps of cubane derivatives are much higher than that of
      triaminotrinitrobenzene (TATB), which means that cubane derivatives may be more
      sensitive than TATB. Polynitraminecubanes have high and positive heats of
      formation, and a good linear relationship between heats of formation and
      nitramine group numbers was presented. As the number of nitramine groups in the
      molecule increases, the enthalpies of combustion values are increasingly
      negative, but the specific enthalpy of combustion values decreases. It is found
      that all cubane derivatives have high strain energies, which are affected by the
      number and position of nitramine group. The calculated bond dissociation energies
      of C-NHNO(2) and C-C bond show that the C-C bond should be the trigger bond in
      the pyrolysis process. It is found that detonation velocity (D), detonation
      pressure (P) and molecule density (rho) have good linear relationship with
      substituented group numbers. Heptanitraminecubane and octanitraminecubane have
      good detonation performance over 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane
      (HMX), and they can be regarded as potential candidates of high energy density
      compounds (HEDCs). The results have not only shown that these compounds may be
      used as HEDCs, but also provide some useful information for further
      investigation.

PMID- 22961624
TI  - Mothers who kill: evolutionary underpinnings and infanticide law.
AB  - Women who kill their children present a profound challenge to accepted notions of
      motherhood and the protection offered by mothers to their children. Historically,
      societies have varied in the sanctions applied to perpetrators of such acts,
      across both time and place. Where penalties were once severe and punitive for
      mothers, in modern times some two dozen nations now have infanticide acts that
      reduce the penalties for mothers who kill their infants. Embedded within these
      acts are key criteria that relate (a) only to women who are (b) suffering the
      hormonal or mood effects of pregnancy/lactation at the time of the offence which
      is (c) usually restricted to within the first year after delivery. Criticisms of
      infanticide legislation have largely centered on inherent gender bias,
      misconceptions about the hormonal basis of postpartum psychiatric disorders, and
      the nexus and contribution of these disorders to the offending in relation to
      issues of culpability and sentencing. Important differences between female
      perpetrators relative to the age of the child victim have also highlighted
      problems in the implementation of infanticide legislation. For example, women who
      commit neonaticide (murder during the first day of life) differ substantially
      from mentally ill mothers who kill older children. However, despite these
      shortcomings, many nations have in recent years chosen to retain their
      infanticide acts. This article reviews the central controversies of infanticide
      legislation in relation to current research and fundamental fairness. Using
      evolutionary psychology as a theoretical framework to organize this discussion,
      it is argued that infanticide legislation is at best unnecessary and at worst
      misapplied, in that it exculpates criminal intent and fails to serve those for
      whom an infanticide defense might otherwise have been intended.

PMID- 22961625
TI  - The type VI secretion system gene cluster of Salmonella typhimurium: required for
      full virulence in mice.
AB  - Type VI secretion system (T6SS) has increasingly been believed to participate in
      the infection process for many bacterial pathogens, but its role in the virulence
      of Salmonella typhimurium remains unclear. To look into this, we deleted the T6SS
      cluster from the genome of S. typhimurium 14028s and analyzed the phenotype of
      the resulting T6SS knockout mutant (T6SSKO mutant) in vitro and in vivo. We found
      that the T6SSKO mutant exhibited reduced capability in colonizing the spleen and
      liver in an in vivo colonization competition model in BALB/c mice infected by the
      oral route. Additionally, infection via intraperitoneal administration also
      showed that the T6SSKO mutant was less capable of colonizing the mouse spleen and
      liver than the wild-type strain. We did not detect significant differences
      between the T6SSKO and wild-type strains in epithelial cell invasion tests.
      However, in the macrophage RAW264.7 cell line, the T6SSKO mutant survived and
      proliferated significantly more poorly than the wild-type strain. These findings
      indicate that T6SS gene cluster is required for full virulence of S. typhimurium
      14028s in BALB/c mice, possibly due to its roles in bacterial survival and
      proliferation in macrophages. 

PMID- 22961626
TI  - Oral cancer-associated fibroblasts inhibit heat-induced apoptosis in Tca8113
      cells through upregulated expression of Bcl-2 through the Mig/CXCR3 axis.
AB  - The aim of this study was to detect oral cancer-associated fibroblast-secreted
      cytokines and their regulation of heat-induced apoptosis in the human tongue
      squamous cell carcinoma cell line Tca8113. We isolated cancer-associated
      fibroblasts (CAFs) from human tongue squamous cell carcinoma and normal
      fibroblasts (NFs) from normal oral mucosa. The expression profiles of cytokines
      secreted by CAFs and those secreted by NFs were detected using the RayBio(r)
      human cytokine antibody microarray. The conditioned medium was prepared by mixing
      the CAF or NF supernatant cell culture medium with fresh complete medium. The
      expression levels of Bax, Bcl-2 and CXCR3 in Tca8113 cells were detected by
      western blot analysis. The heat-induced apoptosis ratio of the Tca8113 cells was
      detected by propidium iodide staining combined with flow cytometry. The quantity
      of the Mig factor, one of the chemokines secreted by CAFs, was clearly increased
      19-fold when compared with the level in NFs. The conditioned medium of NFs had no
      obvious effect on the expression levels of Bax/Bcl-2 and the heat-induced
      apoptosis ratio in the Tca8113 cells. However, the expression levels of Bcl-2
      were significantly upregulated and heat-induced Tca8113 cell apoptosis was
      inhibited in the CAF-conditioned medium. After adding neutralizing antibodies
      against Mig or its receptor CXCR3, the enhanced expression of the Bcl-2 protein
      and the inhibited heat-induced apoptosis of Tca8113 cells in the CAF-conditioned
      medium were significantly attenuated. CAFs may increase the expression levels of
      Bcl-2 through the paracrine secretion of Mig and reduce the thermosensitivity of
      Tca8113 cells.

PMID- 22961627
TI  - Serine/threonine-protein phosphatase 2A physically interacts with human
      telomerase reverse transcriptase hTERT and regulates its subcellular
      distribution.
AB  - Telomerase plays fundamental roles in bypassing cellular aging and promoting
      cancer progression by maintaining telomere homeostasis and telomere-independent
      activities. However, the molecular mechanisms by which telomerase provokes aging
      and cancer are far from being fully understood. In a search for proteins
      interacting with human telomerase reverse transcriptase hTERT by the yeast two
      hybrid screen using hTERT T-motif as bait, we identified PP2A scaffolding subunit
      PR65 alpha isoform as an hTERT interacting partner. We showed that both PP2A
      catalytic subunit PP2AC and scaffolding subunit PR65 interacted with hTERT in
      vivo and in vitro and inhibited telomerase activity. In addition, we found that
      PP2A prevented the interaction of hTERT with 14-3-3theta signaling protein, an
      hTERT binding partner that is required for nuclear localization of hTERT.
      Activation of PP2A by overexpression of PP2AC or PR65 led to cytoplasmic
      accumulation of hTERT, which was reversed by treatment with PP2A inhibitor
      okadaic acid. Together, these observations suggest that PP2A regulates hTERT
      subcellular localization, in addition to its inhibitory effects on telomerase
      activity.

PMID- 22961628
TI  - Mdm2 antagonists induce apoptosis and synergize with cisplatin overcoming
      chemoresistance in TP53 wild-type ovarian cancer cells.
AB  - Ovarian cancer (OVCa) is the leading cause of death from gynecological
      malignancies. Although treatment for advanced OVCa has improved with the
      introduction of taxane-platinum chemotherapy, the majority of patients will
      develop resistance to the treatment, leading to poor prognosis. One of the causes
      of chemoresistance is the reduced ability to undergo apoptosis. Cisplatin is a
      genotoxic drug that leads cells to apoptosis through the activation of the p53
      pathway. Defective signaling in this pathway compromises p53 function, and thus
      cisplatin does not induce apoptosis. A new group of nongenotoxic small molecules
      called Nutlins have been developed to inhibit p53-Mdm2 binding, inducing
      apoptosis in chemoresistant tumors through the activation of the p53 pathway. The
      wild-type p53 cisplatin-resistant ovarian cancer cell-line A2780cis was used to
      test the effect of Nutlin-3a (Nut3a) on apoptosis response. The results showed
      that Nut3a synergized with cisplatin, inducing cell-cycle arrest in G2/M and
      potentiating apoptotic cell death. Increased apoptosis was also induced in wild
      type TP53 primary OVCa cultures by double cisplatin-Nut3a treatment. In
      conclusion, Nut3a appears to sensitize chemoresistant OVCa cells to cisplatin,
      inducing apoptosis. As increased response was generalized in primary tumors, this
      cisplatin-Nut3a combination could be useful for the treatment of patients
      harboring wild-type TP53 who do not respond to standard chemotherapy.

PMID- 22961629
TI  - Label-free polypeptide-based enzyme detection using a graphene-nanoparticle
      hybrid sensor.
AB  - A graphene-nanoparticle (NP) hybrid biosensor that utilizes an electrical
      hysteresis change to detect the enzymatic activity and concentration of
      Carboxypeptidase B was developed. The results indicate that the novel graphene-NP
      hybrid biosensor, utilizing electrical hysteresis, has the ability to detect
      concentrations of targeted enzyme on the micromolar scale. Furthermore, to the
      knowledge of the authors, this is the first demonstration of a graphene-based
      biosensor that utilizes a hysteresis change resulting from metallic NPs assembled
      on a graphene surface.

PMID- 22961630
TI  - Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence
      rates in patients with hepatocellular carcinoma.
AB  - The role of CD4(+) cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC)
      remains obscure. This study characterized CD4(+) CTLs in HCC patients and further
      elucidated the associations between CD4(+) CTLs and HCC disease progression. In
      all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis
      (LC) patients, and 88 healthy individuals were enrolled in the study. CD4(+) CTLs
      were defined by flow cytometry, immunohistochemistry, and lytic granule
      exocytosis assays. A multivariate analysis of prognostic factors for overall
      survival was performed using the Cox proportional hazards model. Circulating and
      liver-infiltrating CD4(+) CTLs were found to be significantly increased in HCC
      patients during early stage disease, but decreased in progressive stages of HCC.
      This loss of CD4(+) CTLs was significantly correlated with high mortality rates
      and reduced survival time of HCC patients. In addition, the proliferation,
      degranulation, and production of granzyme A, granzyme B, and perforin of CD4(+)
      CTLs were inhibited by the increased forkhead/winged helix transcription factor
      (FoxP3(+) ) regulatory T cells in these HCC patients. Further analysis showed
      that both circulating and tumor-infiltrating CD4(+) CTLs were independent
      predictors of disease-free survival and overall survival after the resection of
      the HCC. CONCLUSION: The progressive deficit in CD4(+) CTLs induced by increased
      FoxP3(+) regulatory T cells was correlated with poor survival and high recurrence
      rates in HCC patients. These data suggest that CD4(+) CTLs may represent both a
      potential prognostic marker and a therapeutic target for the treatment of HCC.

PMID- 22961631
TI  - Generation of diversity by somatic mutation in the Camelus dromedarius T-cell
      receptor gamma variable domains.
AB  - In jawed vertebrates the V-(D)-J rearrangement is the main mechanism generating
      limitless variations of antigen-specific receptors, immunoglobulins (IGs), and T
      cell receptors (TCRs) from few genes. Once the initial diversity is established
      in primary lymphoid organs, further diversification occurs in IGs by somatic
      hypermutation, a mechanism from which rearranged TCR genes were thought to be
      excluded. Here, we report the locus organization and expression of the T-cell
      receptor gamma (TCRG) genes in the Arabian camel (Camelus dromedarius).
      Expression data provide evidence that dromedary utilizes only two TCRG V-J
      genomic arrangements and, as expected, CDR3 contributes the major variability in
      the V domain. The data also suggest that diversity might be generated by mutation
      in the productively rearranged TCRGV genes. As for IG genes, the mutational
      target is biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW). The
      replacement and synonymous substitutions (R/S) ratios in TCRGV regions are higher
      for CDR than for framework region, thus suggesting selection toward amino acid
      changes in CDR. Using the counterpart human TCR gammadelta receptor as a
      template, structural models computed adopting a comparative procedure show that
      nonconservative mutations contribute to diversity in CDR2 and at the gammadelta V
      domain interface.

PMID- 22961632
TI  - Enantioselective decarboxylative amination: synthesis of axially chiral allenyl
      amines.
AB  - Getting axed: synthesis of the title amines, bearing functionality (R(1) and
      R(2)), involves the enantioselective palladium-catalyzed decarboxylation of
      allenyl N-tosylcarbamates. The reaction proceeds smoothly using both the chiral
      ligands (S)- and (R)-DTBM-Segphos (1) to afford the allenyl amines in good yields
      and with high enantioseletivities.

PMID- 22961633
TI  - Hepatoprotective effect of bis(4-methylbenzoyl) diselenide against CCl(4)-induced
      oxidative damage in mice.
AB  - From a pharmacological point of view, organoseleniums are compounds with
      important and interesting antioxidant and biological activities. The aim of this
      study was to evaluate the hepatoprotective effect of bis(4-methylbenzoyl)
      diselenide (BMD) against carbon tetrachloride (CCl4 )-induced oxidative damage in
      mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl4
      (1 mg/kg body weight) was administered by intraperitoneal route. One day after
      the CCl4 exposure, the animals were euthanized for biochemical and histological
      analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl
      transferase and lactate dehydrogenase activity increases induced by CCl4 plasma
      exposure. Treatment with BMD (25 mg/kg) protected against increases in
      thiobarbituric reactive species and decreasing non-protein thiols and ascorbic
      acid levels in liver of mice. Catalase and superoxide dismutase activity
      inhibition in the liver caused by CCl4 were protected by treatment with BMD (25
      mg/kg). Glutathione S-transferase activity was inhibited by CCl4 and remained
      unaltered even after treatment with BMD. Sections of liver from CCl4 -exposed
      mice presented an intense infiltration of inflammatory cells and loss of the
      cellular architecture. BMD (25 mg/kg) attenuated CCl4 -induced hepatic
      histological alterations. The results demonstrated the hepatoprotective effects
      of BMD in the mouse liver, possibly by modulating the antioxidant status.

PMID- 22961634
TI  - Mortality and morbidity in adult craniopharyngioma.
AB  - A craniopharyngioma (CP) is an embryonic malformation of the sellar and
      parasellar region. The annual incidence is 0.5-2.0 cases/million/year and
      approximately 60 % of CP are seen in adulthood. Craniopharyngiomas have the
      highest mortality of all pituitary tumors. Typical initial manifestations at
      diagnosis in adults are visual disturbances, hypopituitarism and symptoms of
      elevated intracranial pressure. The long-term morbidity is substantial with
      hypopituitarism, increased cardiovascular risk, hypothalamic damage, visual and
      neurological deficits, reduced bone health, and reduction in quality of life and
      cognitive function. Therapy of choice is surgery, followed by cranial
      radiotherapy in about half of the patients. The standardised overall mortality
      rate varies 2.88-9.28 in cohort studies. Patients with CP have a 3-19 fold higher
      cardiovascular mortality in comparison to the general population. Women with CP
      have an even higher risk.

PMID- 22961635
TI  - Real time visualization of femoroacetabular impingement and subluxation using 320
      slice computed tomography.
AB  - We visualized extreme ranges of motion of the hip and located femoroacetabular
      impingement (FAI) and subluxations using 4dimensional (D) volume computed
      tomography (CT). In dynamic 4D CT, 30 patients with hip pain (>3 months) and
      positive clinical and radiological signs of impingement were prospectively
      analyzed. The investigations were performed in flexion, abduction, and external
      rotation. The accuracy of the CT visualization of FAI was compared with the
      intraoperative findings during surgical dislocation, which served as the gold
      standard. Compared to the intraoperative visualization of FAI, the dynamic CT
      images showed a high degree of accuracy. 4D CT is a suitable method to
      dynamically visualize the functional consequences of anatomical FAI pathologies.
      The location of impingement can be accurately determined, and when combined with
      information about possible labral tears and chondral damage supplied by magnetic
      resonance arthrography, allows the surgeon to select the optimal surgical access
      and plan the required operation for minimal invasiveness.

PMID- 22961636
TI  - The differential diagnosis of tongue swelling.

PMID- 22961637
TI  - Bleeding complications in pediatric ABO-incompatible kidney transplantation.
AB  - BACKGROUND: ABO-incompatible renal transplantation (ABOi-RTx) following
      preconditioning with immunoadsorption (IA) and rituximab is a promising approach
      to facilitate living-related RTx. However, clinical experience is limited in
      pediatric patients. METHODS: Three patients underwent living-related ABOi-RTx in
      our center. Preoperative IA was performed six, ten and 11 times in patient one,
      two and three, respectively, to achieve isoagglutinin titers of <=1:8 on the day
      of transplantation; rituximab was administered once. The immunosuppressive
      regimen further comprised tacrolimus, mycophenolate, methylprednisolone and
      basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx. RESULTS:
      All three patients achieved normal renal function within 2-6 days post-RTx. Major
      postoperative bleeding occurred in two patients, with one requiring repeated
      blood transfusions and the other a surgical revision 4 h after RTx, despite local
      citrate anticoagulation use during the preoperative IA procedures in the latter
      patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers
      to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third
      patient, which was treated successfully with plasma exchange and
      methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and
      23 months post-RTx was 96, 52 and 74 ml/min/1.73 m(2), respectively. CONCLUSIONS:
      ABOi-RTx can successfully be performed in pediatric patients after
      preconditioning with quadruple immunosuppression, rituximab and IA. Caution is
      required regarding bleeding complications, which are most likely due to the
      unspecific binding of coagulation factors during repeated IA.

PMID- 22961639
TI  - Biotechnological and safety characterization of Enterococcus lactis, a recently
      described species of dairy origin.
AB  - The biotechnological and safety properties of a recently described enterococcal
      species, Enterococcus lactis, were investigated. With regard to the technological
      properties, in milk all the strains tested had weak acidifying and proteolytic
      activities, generally medium reduction activity over 24 h (-102 mV < Eh < -2 mV)
      and low lipolytic activity on tributyrin agar. The isolates were tested for
      resistance against 14 antibiotics and none of the studied strains were classified
      as resistant to clinically important antibiotics such as ampicillin,
      erythromycin, penicillin G, tetracycline and vancomycin. Furthermore, PCR-based
      detection did not identify any of the common genetic determinants for vancomycin,
      tetracycline and erythromycin resistance. The E. lactis strains showed good
      survival in simulated in vitro digestion and were able to inhibit the growth of
      Enterococcus  durans, Enterococcus  faecalis, Enterococcus  faecium, Clostridium
      sporogenes, Clostridium tyrobutyricum and Pseudomonas syringae. Screening for
      enterocin structural genes showed that all isolates harboured the entP gene. The
      presence of nine virulence factor genes (cylA, asa1, gelE, hyl, esp, ace, efaA,
      hdc and tdc) was investigated by PCR and no virulence determinants were detected.
      This study highlights that the recently described E. lactis may be a potential
      source of novel strains with interesting features that could be used for
      fermented dairy foods.

PMID- 22961640
TI  - A newly developed double lumen microballoon catheter with a side hole: initial
      experience of intraarterial infusion chemotherapy and/or embolization.
AB  - PURPOSE: To introduce a newly developed double lumen microballoon catheter with a
      side hole for intraarterial infusion chemotherapy and/or embolization. METHODS
      AND MATERIALS: Seven patients with malignant tumors, for whom superselective
      catheterization was considered difficult or had failed, underwent intraarterial
      infusion chemotherapy and/or embolization with the 3.3-Fr microballoon catheter.
      The catheter has a double lumen and a side hole to facilitate infusion from the
      proximal end of the balloon. The balloon was placed on the distal side of the
      target artery branching site. Inflation of the balloon and occlusion of the main
      lumen with the tip of the occlusion device allowed for intraarterial infusion
      chemotherapy and/or embolization of the target artery via the side hole. RESULTS:
      Successful intraarterial infusion chemotherapy and/or embolization with the
      microballoon catheter was performed in all patients with no complications.
      CONCLUSIONS: The newly developed microballoon catheter achieves intraarterial
      infusion chemotherapy and/or embolization without the need for superselective
      catheterization.

PMID- 22961642
TI  - A conidiation-related gene is highly expressed at the resting urediospore stage
      in Puccinia striiformis f. sp. tritici.
AB  - The production and germination of asexual spores in a diverse group of fungi play
      a crucial role in their infection cycles. These processes are regulated by a set
      of genes, namely, conidiation-related genes, involved in the production,
      morphological characteristics, and differentiation of conidia. In this study, we
      identified and characterized the PsCon1 gene, which is the first conidiation
      related gene identified in Puccinia striiformis f. sp. tritici (Pst). Sequence
      analysis revealed that PsCON1 has two conserved conidiation-specific protein 6
      domains. Single nucleotide polymorphisms and insertion/deletion variations were
      detected in the coding region of PsCon1 among five Pst races. Quantitative RT-PCR
      assays revealed that PsCon1 was expressed at the highest level in resting
      urediospores of Pst, and gradually decreased after germination and infection.
      However, at 312 hpi, at the stage of forming large amounts of urediospores on
      leaves, the amount of PsCon1 mRNA was sharply increased but only 0.1-fold that of
      resting urediospores. Subcellular localization assays indicated PsCon1
      heterologously expressed in Fusarium graminearum was located in the cytoplasm of
      conidia. The results suggest that PsCon1 may play a role in formation or survival
      of Pst urediospores. 

PMID- 22961641
TI  - Histone deacetylase inhibitors stimulate dedifferentiation of human breast cancer
      cells through WNT/beta-catenin signaling.
AB  - Recent studies have shown that differentiated cancer cells can dedifferentiate
      into cancer stem cells (CSCs) although to date no studies have reported whether
      this transition is influenced by systemic anti-cancer agents. Valproic acid (VA)
      is a histone deacetylase (HDAC) inhibitor that promotes self-renewal and
      expansion of hematopoietic stem cells and facilitates the generation of induced
      pluripotent stem cells from somatic cells and is currently being investigated in
      breast cancer clinical trials. We hypothesized that HDAC inhibitors reprogram
      differentiated cancer cells toward the more resistant stem cell-like state. Two
      highly aggressive breast cancer cell lines, SUM159 and MDA-231, were sorted based
      on aldehyde dehydrogenase (ALDH) activity and subsequently ALDH-negative and ALDH
      positive cells were treated with one of two known HDAC inhibitors, VA or
      suberoylanilide hydroxamic acid. In addition, primary tumor cells from patients
      with metastatic breast cancer were evaluated for ALDH activity following
      treatment with HDAC inhibitors. We demonstrate that single-cell-sorted ALDH
      negative cells spontaneously generated ALDH-positive cells in vitro. Treatment of
      ALDH-negative cells with HDAC inhibitors promoted the expansion of ALDH-positive
      cells and increased mammosphere-forming efficiency. Most importantly, it
      significantly increased the tumor-initiating capacity of ALDH-negative cells in
      limiting dilution outgrowth assays. Moreover, while HDAC inhibitors upregulated
      beta-catenin expression and significantly increased WNT reporter activity, a TCF4
      dominant negative construct abolished HDAC-inhibitor-induced expansion of CSCs.
      These results demonstrate that HDAC inhibitors promote the expansion of breast
      CSCs through dedifferentiation and have important clinical implications for the
      use of HDAC inhibitors in the treatment of cancer.

PMID- 22961643
TI  - C-F bond activation with an apparently benign ethynyl dithiocarbamate, and
      subsequent fluoride transfer reactions.
AB  - F-act finding mission: Selective activation of the para C-F bonds of
      perfluorinated aromatic derivatives was achieved with a simple ethynyl
      dithiocarbamate. The resulting adducts can be used as non-ionic, anhydrous
      fluoride transfer reagents towards various electrophiles (see scheme).

PMID- 22961644
TI  - Recurrent non-small cell lung cancer: evaluation of CT-guided radiofrequency
      ablation as salvage therapy.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a potential application as a salvage
      tool after failure of surgery, chemotherapy, or radiotherapy of non-small cell
      lung cancer (NSCLC). Although several studies have evaluated the use of RFA in
      primary NSCLC, there is little literature on its potential application as a
      salvage tool. PURPOSE: To evaluate CT-guided RFA employed as a salvage therapy
      for pulmonary recurrences of NSCLC after prior treatment with chemotherapy,
      radiation therapy, and/or surgery. MATERIAL AND METHODS: A retrospective computer
      database search yielded 33 patients with biopsy proven primary NSCLC who
      underwent CT-guided RFA of 39 recurrent tumors following surgery, chemotherapy,
      and/or radiotherapy. Follow-up imaging was performed with CT and PET-CT. The
      endpoints of interest were progression-free survival (PFS) and time to local
      progression (TTLP). PFS and TTLP were compared by lesion size (<3 cm, >=3 cm).
      RESULTS: The median PFS was 8 months. For patients with a tumor size <3 cm median
      PFS was 11 months, whereas the median PFS of patients with a tumor size >=3 cm
      was 5 months. The difference did not reach statistical significance (P = 0.09).
      The median TTLP of all tumors was 14 months. TTLP of ablated tumors <3 cm in size
      was 24 months, compared to 8 months for ablated tumors >=3 cm in size. The
      difference did not reach statistical significance (P = 0.07). CONCLUSION: RFA of
      recurrent NSCLC may be a valuable salvage tool to achieve local tumor control,
      especially in tumors measuring <3 cm in size.

PMID- 22961645
TI  - Radiofrequency ablation in a porcine kidney model: effect of occlusion of the
      arterial blood supply on ablation temperature, coagulation diameter, and
      histology.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is susceptible to the cooling effect of
      flowing blood. The reduced efficacy of RFA in large tumors reflects the in vivo
      biophysiological limitations imposed by perfusion-mediated vascular cooling.
      PURPOSE: To compare the effects of RFA alone and of RFA combined with occlusion
      of the arterial blood supply on the tissue temperature, coagulation diameter, and
      histological changes in the acute phase. MATERIAL AND METHODS: The temperature at
      roll-off, the coagulated tissue diameter, and histologic tissue changes were
      compared in normal porcine kidneys subjected in situ to two pigs each were
      subjected to RFA alone (four kidneys) or to RFA plus balloon occlusion of the
      renal artery (four kidneys). The tissue temperature was measured at three sites:
      area I, the center of the RFA field; area II, the ischemic field 1 cm distant
      from the edge of the RFA field; and area III, the normal kidney. Tissue samples
      were stained with hematoxylin and eosin (H&E). Cell viability in the ablated zone
      was determined by nicotinamide adenine dinucleotide (NADH) staining of frozen
      sections. RESULTS: The tissue temperatures achieved by RFA in areas I, II, and
      III were 101 degrees C, 58 degrees C, and 40 degrees C with and 92 degrees C, 44
      degrees C, and 38 degrees C without balloon occlusion, respectively. The maximal
      coagulation diameter was 31 mm with and 23 mm without occlusion. The coagulation
      diameter was significantly larger and the temperature in area II was
      significantly higher in kidneys subjected to RFA with renal artery occlusion. H&E
      staining showed preservation of the normal renal parenchymal structure outside
      the thermal lesion and an increase in eosinophilic cells with indistinct cell
      borders and nuclei within the thermal lesion. H&E and NADH staining demonstrated
      a sharp demarcation between the ablation and normal tissue area and showed that
      in area II the addition of balloon occlusion did not produce histologic changes
      different from those in kidneys subjected to RFA alone. CONCLUSION: A technique
      that combines RFA and partial renal artery occlusion may be useful in treatment
      of the non-resectable renal tumors with sizes appropriate for RF ablation.

PMID- 22961647
TI  - Introduction: clinicians respond to their clients' technology.
AB  - The contributors to this special issue of The Journal of Clinical Psychology: In
      Session have given us a wide range of ideas about technology use among children
      and adolescents, illustrated with rich clinical material. Of the many interesting
      issues they raise, I briefly discuss four that are particularly salient: the
      interaction of technology with personality and development; the concept of
      Internet addiction; the importance of adult guidance and limit setting; and
      technology and clinical creativity. Taken as a whole, these papers suggest that
      while technology can certainly contribute to and help create pathology, it can
      also contribute to growth, and that in either case technology interacts with
      fundamental human needs and developmental processes.

PMID- 22961646
TI  - [Recurrence of hydatid cyst of liver: predictive factors: Tunisian experience].
AB  - Cystic echinococcosis is a public health problem. Surgery represents the basic
      treatment and the surgeon is regularly faced with the choice of the appropriate
      surgical procedure (radical versus conservative surgical approach). The
      conservative procedure is safe and easy but can lead to a recurrence in the site
      of residual cavity. The aim of this study was to evaluate the predictive factors
      of the recurrence of hepatic hydatid cysts, to optimize surgical management and
      to implement preventive measures. The current retrospective study included 391
      patients with hepatic hydatid cysts operated at our institution from 1996 to
      2006. The diagnosis of recurrence was suspected by radiological survey and
      confirmed at laparotomy. The univariate study of predictive factors of recurrence
      was based on the Fisher test and the multivariate one on the logistic regression
      model. The recurrence rate reached 12% in our study with an average period of 50
      months. Univariate analysis showed that the predictive factors of recurrence
      were: the rural origin of patients, the voluminous cysts larger than 7 cm, and
      unilocular hydatid cyst. Multivariate analysis showed that only voluminous cysts
      and unilocular ones were the predictive factors of recurrence. The unilocular and
      voluminous hydatid cysts represent the cysts that relapse frequently because of
      their immunogenic character and the presence of exocysts in the pericysts. This
      is very important for the therapeutic strategy the main aim of which is to
      prevent the recurrence.

PMID- 22961648
TI  - Mortality rate increases steeply with nonadherence to statin therapy in patients
      with acute coronary syndrome.
AB  - BACKGROUND: In a prospective cohort of consecutive acute coronary syndrome (ACS)
      patients, we compared the adherence rate of statin usage and mortality rate
      during a median follow-up of 23 months. HYPOTHESIS: Adherence to statin therapy
      after acute coronary syndrome affects mortality rate. METHODS: We analyzed ACS
      patients (N = 1969; age, 65.9 +/- 11.8 years; female 30.4%) who underwent
      angiography between March 2006 and March 2008. The postdischarge usage of statins
      was based on the purchase register of the Social Insurance Institution of
      Finland. The death rate was verified from Statistics Finland. RESULTS: At
      discharge, the rate of statin prescription to patients was 95.4% (n = 1878). When
      comparing adherent patients (n = 1200; 61.7%), who purchased the medication
      systematically until the end of the median 23-month follow-up, with nonadherent
      patients (n = 94; 4.8%), who did not use the medication at all, there was a vast
      difference in absolute death rate between the groups: 4.9% vs 14.9%, respectively
      (P < 0.001). We conducted Cox proportional hazards model with ACS type,
      cerebrovascular attack, diabetes, age, 3-artery disease, and cancer as adjusted
      confounders. Compared with regular statin users, nonusers were associated with a
      >2* increased hazard ratio of mortality (hazard ratio: 2.70, 95% confidence
      interval: 1.49-4.90, P = 0.001). CONCLUSIONS: Statin medication is essential for
      discharged ACS patients. They should be strongly encouraged to purchase and use
      it.

PMID- 22961649
TI  - Platelet-derived growth factor promotes the proliferation of human umbilical cord
      derived mesenchymal stem cells.
AB  - This study was designed to investigate the effect of platelet-derived growth
      factor (PDGF) on the proliferation of human umbilical cord mesenchymal stem cells
      (UC-MSCs) and further explore the mechanism of PDGF in promoting the
      proliferation of UC-MSCs. The human UC-MSCs were treated with different
      concentrations of PDGF, and the effects were evaluated by counting the cell
      number, the cell viability, the expression of PDGF receptors analyzed by RT-PCR,
      and the detection of the gene expression of cell proliferation, cell cycle and
      pluripotency, and Brdu assay by immunofluorescent staining and Quantitative real
      time (QRT-PCR). The results showed that PDGF could promote the proliferation of
      UC-MSCs in vitro in a dose-dependent way, and 10 to 50 ng/ml PDGF had a
      significant proliferation effect on UC-MSCs; the most obvious concentration was
      50 ng/ml. Significant inhibition on the proliferation of UC-MSCs was observed
      when the concentration of PDGF was higher than 100 ng/ml, and all cells died when
      the concentration reached 200 ng/ml PDGF. The PDGF-treated cells had stronger
      proliferation and antiapoptotic capacity than the control group by Brdu staining.
      The expression of the proliferation-related genes C-MYC, PCNA and TERT and cell
      cycle-related genes cyclin A, cyclin 1 and CDK2 were up-regulated in PDGF medium
      compared with control. However, pluripotent gene OCT4 was not significantly
      different between cells cultured in PDGF and cells analyzed by immunofluorescence
      and QRT-PCR. The PDGF could promote the proliferation of human UC-MSCs in vitro.

PMID- 22961650
TI  - Characterization of proteins secreted by pancreatic cancer cells with anticancer
      drug treatment in vitro.
AB  - Pancreatic cancer is one of the most lethal cancers, with an incidence equaling
      mortality. It is a heterogeneous group of neoplasms in which pancreatic ductal
      adenocarcinoma is most common. Pancreatic cancer cannot be cured even if detected
      early. When treatment is initiated, a suitable method of administration of
      anticancer drugs must be chosen. Anticancer drugs kill tumor cells. However, side
      effects including initiation are problematic in anticancer drug therapy. Improved
      methods for the diagnosis of side effects of pancreatic cancer by using sensitive
      and specific tumor markers are highly desirable. Therefore, efficient strategies
      for biomarker discovery are urgently needed. Here, we present an approach based
      on direct experimental access to proteins released by PANC-1 human pancreatic
      cancer cells in vitro. A two-dimensional (2-D) map and catalog of this
      subproteome, herein termed the secretome, were established comprising more than
      1,000 proteins observed by '2-D difference in-gel electrophoresis analysis using
      cyanine dye'. We investigated 22 spots that were 1.20-fold upregulated and 31
      spots that were 0.66-fold downregulated by gemcitabine chloride treatment.
      Proteins in these spots were identified by nano-high-performance liquid
      chromatography electrospray ionization time of flight mass spectrometry/mass
      spectrometry. Most secretome constituents were nominally cellular proteins. By
      mass spectrometry screening, 14-3-3 protein sigma (14-3-3 sigma), protein S100
      A8, protein S100-A9, galectin-7, lactotransferrin (lactoferrin, LF) precursor,
      serotransferrin (transferrin) precursor, and vitamin D binding protein precursor
      were identified. Western blotting confirmed the presence of 14-3-3 sigma and LF.
      We found that upregulation of 14-3-3 sigma was associated with apoptosis, and
      downregulation of LF was found to suppress tumorigenesis.

PMID- 22961651
TI  - The alpha-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the
      formation of validamycin B.
AB  - From A to B: Through detailed biochemical investigations, we discovered that
      VldW, an alpha-ketoglutarate/Fe(II)-dependent dioxygenase, regioselectively
      hydroxylates validamycin A to validamycin B. The results provide insights into
      the biosynthesis of hydroxylated validamycins and could be used to control the
      metabolic outcomes of the validamycin pathway.

PMID- 22961652
TI  - Unlike alphabeta T cells, gammadelta T cells, LTi cells and NKT cells do not
      require IRF4 for the production of IL-17A and IL-22.
AB  - Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can
      also be produced by gammadelta T cells, NK cells and lymphoid tissue inducer
      (LTi) cells. Th17 cells develop from precursor cells after T-cell receptor
      stimulation in the presence of TGF-beta, IL-6 and IL-23. In contrast, a subset of
      gammadelta T cells ("gammadeltaT17") is committed for fast IL-17 production
      already in the thymus; however, gammadelta T cells can also produce IL-17 after
      prolonged in vitro stimulation via their gammadelta T-cell receptor plus IL-23.
      Here, we show that gammadelta T-, LTi- and NKT cells differ extensively from Th17
      cells in their signalling requirements for the generation of IL-17A and IL-22.
      While production of these cytokines by Th17 cells totally depends on the
      transcription factor interferon regulatory factor 4 (IRF4), IRF4 is irrelevant in
      the other cell types. As for gammadelta T cells, this finding pertains to both
      thymic commitment and prolonged in vitro culture. Furthermore, IL-17A-producing
      gammadelta T cells accumulate in the central nervous system of IRF4 deficient
      (Irf4(-/-)) mice during experimental autoimmune encephalomyelitis. IL-17A
      producing WT and Irf4(-/-) gammadelta T cells equally express CCR6 and lack CD27.
      The underlying IRF4-independent pathway partially involves STAT3 during in vitro
      stimulation.

PMID- 22961654
TI  - 2,4,6-Trinitrotoluene: a surprisingly insensitive energetic fuel and binder in
      melt-cast decoy flare compositions.

PMID- 22961653
TI  - Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites
      inhibit farnesoid X receptor resulting in a cholestatic phenotype.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy
      specific liver disease and is associated with an increased risk of adverse fetal
      outcomes, including preterm labor and intrauterine death. The endocrine signals
      that cause cholestasis are not known but 3alpha-sulfated progesterone metabolites
      have been shown to be elevated in ICP, leading us to study the impact of sulfated
      progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid
      homeostasis pathways. Here we report that the 3beta-sulfated progesterone
      metabolite epiallopregnanolone sulfate is supraphysiologically raised in the
      serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia
      and a hepatic gene expression profile indicative of FXR activation. However,
      coadministration of epiallopregnanolone sulfate with cholic acid exacerbated the
      hypercholanemia and resulted in aberrant gene expression profiles for hepatic
      bile acid-responsive genes consistent with cholestasis. We demonstrate that
      levels of epiallopregnanolone sulfate found in ICP can function as a partial
      agonist for FXR, resulting in the aberrant expression of bile acid homeostasis
      genes in hepatoma cell lines and primary human hepatocytes. Furthermore,
      epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated
      bile acid efflux and secreted FGF19. Using cofactor recruitment assays, we show
      that epiallopregnanolone sulfate competitively inhibits bile acid-mediated
      recruitment of cofactor motifs to the FXR-ligand binding domain. CONCLUSION: Our
      results reveal a novel molecular interaction between ICP-associated levels of the
      3beta-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that
      couples the endocrine component of pregnancy in ICP to abnormal bile acid
      homeostasis.

PMID- 22961655
TI  - Robotic tentacles with three-dimensional mobility based on flexible elastomers.
AB  - Soft robotic tentacles that move in three dimensions upon pressurization are
      fabricated by composing flexible elastomers with different tensile strengths
      using soft lithographic molding. These actuators are able to grip complex shapes
      and manipulate delicate objects. Embedding functional components into these
      actuators (for example, a needle for delivering fluid, a video camera, and a
      suction cup) extends their capabilities.

PMID- 22961656
TI  - Correlations of HOMA2-IR and HbA1c with algorithms derived from bioimpedance and
      spectrophotometric devices.
AB  - BACKGROUND: Homeostasis model assessment of insulin resistance (HOMA2-IR) and
      HbA1c, markers of metabolic syndrome and glycemic control, were compared with
      Electro Sensor (ES) Complex software algorithms. ES complex software integrates
      data from Electro Sensor Oxi (ESO; spectrophotometry) and Electro Sensor-Body
      Composition (ES-BC; bioimpedance). METHODS: One hundred forty-eight Brazilian
      obese candidates for bariatric surgery underwent complete physical examinations,
      laboratory tests (fasting plasma glucose, fasting plasma insulin, and HbA1c) and
      ES complex assessments. HOMA2-IR was calculated from fasting plasma glucose and
      fasting plasma insulin using free software provided by The University of Oxford
      Diabetes Trial Unit. ES complex-insulin resistance (ESC-IR) and ES complex-blood
      glucose control (ESC-BCG) were calculated from ESO and ES-BC data using ES
      complex software. Correlations between HOMA2-IR and ESC-IR and between ESC-BGC
      and HbA1c were determined. RESULTS: ESC-BGC was correlated with HbA1c (r = 0.85).
      ESC-BCG values >3 were predictive of HbA1c > 6.5% (phi = 0.94; unweighted kappa =
      0.9383). ESC-IR was correlated with HOMA2-IR (r = 0.84). Patients with ESC-IR
      score >2.5 or >3 were more likely to have metabolic syndrome or insulin
      resistance, respectively, compared with HOMA2-IR value >1.4 and >1.8,
      respectively. ESC-IR performance was evaluated by receiver operating
      characteristic curves. The areas under the curve for metabolic syndrome and
      insulin resistance were 0.9413 and 0.9022, respectively. CONCLUSION: The results
      of this study in Brazilian subjects with obesity suggest that ES complex
      algorithms will be useful in large-scale screening studies to predict insulin
      resistance, metabolic syndrome, and HbA1c >6.5%. Additional studies are needed to
      confirm these correlations in non-obese subjects and in other ethnic groups.

PMID- 22961657
TI  - Limited effect of reactive oxygen species on the composition of susceptible
      essential amino acids in the midguts of Lymantria dispar caterpillars.
AB  - The essential amino acids (EAAs) arginine, histidine, lysine, and methionine, as
      well as cysteine (semiessential), are believed to be susceptible to reactions
      with reactive oxygen species (ROS) in biological systems. The decreased
      availability of these EAAs could harm insect nutrition, since several of them can
      also be limiting for protein synthesis. However, no in vivo studies have
      quantified the effect of ROS in the midguts of insect herbivores on EAA
      composition. This study examined the association between elevated levels of ROS
      in the midgut fluid of Lymantria dispar caterpillars and the compositions of EAAs
      (protein-bound + protein-free) in their midgut fluid and frass. Contrary to
      expectation, the compositions of EAAs were not significantly decreased by ROS in
      midgut fluid ex vivo when incubated with phenolic compounds. Two in vivo
      comparisons of low- and high-ROS-producing leaves also showed similar results:
      there were no significant decreases in the compositions of EAAs in the midgut
      fluids and/or frass of larvae with elevated levels of ROS in their midguts. In
      addition, waste nitrogen excretion was not significantly increased from larvae on
      high-ROS treatments, as would be expected if ROS produced unbalanced EAA
      compositions. These results suggest that L. dispar larvae are able to tolerate
      elevated levels of ROS in their midguts without nutritionally significant changes
      in the compositions of susceptible EAAs in their food.

PMID- 22961658
TI  - Hypoxia and hypoxia-inducible factors as regulators of T cell development,
      differentiation, and function.
AB  - Oxygen is a molecule that is central to cellular respiration and viability, yet
      there are multiple physiologic and pathological contexts in which cells
      experience conditions of insufficient oxygen availability, a state known as
      hypoxia. Given the metabolic challenges of a low oxygen environment, hypoxia
      elicits a range of adaptive responses at the cellular, tissue, and systemic level
      to promote continued survival and function. Within this context, T lymphocytes
      are a highly migratory cell type of the adaptive immune system that frequently
      encounters a wide range of oxygen tensions in both health and disease. It is now
      clear that oxygen availability regulates T cell differentiation and function, a
      response orchestrated in large part by the hypoxia-inducible factor transcription
      factors. Here, we discuss the physiologic scope of hypoxia and hypoxic signaling,
      the contribution of these pathways in regulating T cell biology, and current gaps
      in our understanding. Finally, we discuss how emerging therapies that modulate
      the hypoxic response may offer new modalities to alter T cell function and the
      outcome of acute and chronic pathologies.

PMID- 22961659
TI  - A canonical Vgamma4Vdelta4+ gammadelta T cell population with distinct
      stimulation requirements which promotes the Th17 response.
AB  - We previously reported a subset of gammadelta T cells in mice which
      preferentially responds following intradermal immunization with collagen in
      complete Freund's adjuvant (CFA). These cells express a nearly invariant
      "canonical" Vgamma4Vdelta4+ TCR. They are potent producers of IL-17A and promote
      the development of collagen-induced arthritis. In this study, we report that CFA
      emulsified with PBS alone (without collagen) is sufficient to induce a strong
      response of Vgamma4Vdelta4+ cells in the draining lymph nodes of DBA/1 and
      C57BL/6 mice and that the TCRs of the elicited Vgamma4Vdelta4+ cells in both
      strains heavily favor the canonical sequence. However, although both CFA and
      incomplete Freund's adjuvant (which lacks the killed mycobacteria present in CFA)
      induced Vgamma4Vdelta4+ gammadelta T cell to expand, only CFA stimulated them to
      express IL-17A. The route of immunization was also critical, since
      intraperitoneal CFA induced only a weak response by these cells, whereas
      intradermal or subcutaneous CFA strongly stimulated them, suggesting that the
      canonical CFA-elicited Vgamma4Vdelta4+ cells are recruited from Vgamma4+
      gammadelta T cells normally found in the dermis. Their IL-17A response requires
      the toll-like receptor adapter protein MyD88, and their activation is enhanced by
      IFNgamma, although alphabeta T cells need not be present. The CFA-elicited
      Vgamma4Vdelta4+ gammadelta T cells show a cytokine profile different from that of
      other previously described IL-17-producing gammadelta T cells. Finally, the
      Vgamma4Vdelta4+ subset appears to promote the Th17 alphabeta T cell response,
      suggesting its importance in mounting an effective immune response against
      certain pathogens.

PMID- 22961660
TI  - Humoral immunity in the Friend retrovirus infection model.
AB  - Major conceptual roadblocks impede the development of an HIV-1 vaccine that can
      stimulate a potent neutralizing antibody response. Animal models that support HIV
      1 replication and allow for host genetic manipulation would be an ideal platform
      for testing various immunological hypotheses, but progress on this research front
      has been slow and disappointing. In contrast, many valuable concepts emerged from
      more than 50 years of studying the Friend retrovirus model. This was recently
      exemplified by the identification of an innate restriction gene, Apobec3, that
      could promote the retrovirus-specific neutralizing antibody response. Here we
      review both classical and recent data on humoral immunity against Friend
      retrovirus infection, and highlight the potential of this model for unraveling
      novel aspects of the retrovirus-specific antibody response that may guide HIV-1
      vaccine development efforts.

PMID- 22961661
TI  - Microarray analysis of Drosophila dicer-2 mutants reveals potential regulation of
      mitochondrial metabolism by endogenous siRNAs.
AB  - RNA interference is a eukaryotic regulatory mechanism by which small non-coding
      RNAs typically mediate specific silencing of their cognate genes. In Drosophila,
      the RNase III enzyme Dicer-2 (Dcr-2) is essential for biogenesis of endogenous
      small interfering RNAs (endo-siRNAs), which have been implicated in regulation of
      endogenous protein-coding genes. Although much is known about microRNA-based
      regulatory networks, the biological functions of endo-siRNAs in animals remain
      poorly understood. We performed gene expression profiling on Drosophila dcr-2
      null mutant pupae to investigate transcriptional effects caused by a severe
      defect in endo-siRNA production, and found 306 up-regulated and 357 down
      regulated genes with at least a twofold change in expression compared with the
      wild type. Most of these up-regulated and down-regulated genes were associated
      with energy metabolism and development, respectively. Importantly, mRNA sequences
      of 39% of the up-regulated genes were perfectly complementary to the sequences of
      previously reported endo-siRNAs, suggesting they may be direct targets of endo
      siRNAs. We confirmed up-regulation of five selected genes matching endo-siRNAs
      and concomitant down-regulation of the corresponding endo-siRNAs in dcr-2 mutant
      pupae. Most of the potential endo-siRNA target genes were associated with energy
      metabolism, including the citric acid cycle and oxidative phosphorylation in
      mitochondria, implying that these are major metabolic processes directly affected
      by endo-siRNAs in Drosophila. Consistent with this finding, dcr-2 null mutant
      pupae had lower ATP content compared with controls, indicating that mitochondrial
      energy production is impaired in these mutants. Our data support a potential role
      for the endo-siRNA pathway in energy homeostasis through regulation of
      mitochondrial metabolism.

PMID- 22961662
TI  - Graphite oxides: effects of permanganate and chlorate oxidants on the oxygen
      composition.
AB  - Research on graphene materials has refocused on graphite oxides (GOs) in recent
      years. The fabrication of GO is commonly accomplished by using concentrated
      sulfuric acid in conjunction with: a) fuming nitric acid and KClO(3) oxidant
      (Staudenmaier); b) concentrated nitric acid and KClO(3) oxidant (Hofmann); c)
      sodium nitrate for in situ production of nitric acid in the presence of KMnO(4)
      (Hummers); or d) concentrated phosphoric acid with KMnO(4) (Tour). These methods
      have been used interchangeably in the graphene community, since the properties of
      GOs produced by these different methods were assumed as almost similar. In light
      of the wide applicability of GOs in nanotechnology applications, in which
      presence of certain oxygen functional groups are specifically important, the
      qualities and functionalities of the GOs produced by using these four different
      methods, side-by-side, was investigated. The structural characterizations of the
      GOs would be probed by using high resolution X-ray photoelectron spectroscopy,
      nuclear magnetic resonance, Fourier transform infrared spectroscopy, and Raman
      spectroscopy. Further electrochemical applicability would be evaluated by using
      electrochemical impedance spectroscopy and cyclic voltammetry techniques. Our
      analyses highlighted that the oxidation methods based on permanganate oxidant
      (Hummers and Tour methods) gave GOs with lower heterogeneous electron-transfer
      rates and a higher amount of carbonyl and carboxyl functionalities compared with
      when using chlorate oxidant (Staudenmaier and Hofmann methods). These
      observations indicated large disparities between the GOs obtained from different
      oxidation methods. Such insights would provide fundamental knowledge for fine
      tuning GO for future applications.

PMID- 22961663
TI  - Constitutive activation of brassinosteroid signaling in the Arabidopsis elongated
      D/bak1 mutant.
AB  - Defects in brassinosteroid (BR) biosynthetic or signaling genes result in dwarfed
      plants, whereas overexpression of these genes increases overall stature. An
      Arabidopsis elongated-D (elg-D) mutant shares phenotypic similarities with BR
      overexpression lines, suggesting its implication in BR pathways. Here, we
      determine how elg-D affects BR signaling. Since elg-D rescued dwarfism in bri1-5
      plants, a BR receptor mutant, but not in BR-insensitive bin2/dwf12-1D plants, elg
      D appears to act between bri1-5 and bin2/dwf12-1D in BR signaling. We found that
      elg-D had an increased response to epi-brassinolide (epi-BL); that the BES1
      transcription factor was shifted toward the dephosphorylated form in elg-D; that
      the expression of a BR responsive gene, SAUR-AC1, was upregulated in elg-D; and
      that transcription of BR biosynthetic genes, DWF4 and CPD, was downregulated by
      feedback inhibition. Thus, endogenous levels of CS and BL as well as biosynthetic
      intermediates were reduced by the elg-D mutation, whereas basal levels of BR
      signaling were elevated. Map-based cloning and sequencing revealed that elg-D is
      allelic to the BR co-receptor protein, BAK1, and has an Asp(122) to Asn
      substitution in the third repeat of the extracellular leucine-rich repeat (LRR)
      domain. In agreement with the finding that BAK1/ELG is involved in the perception
      of pathogen-associated molecular patterns (PAMPs), the bak1/elg-D plants
      exhibited increased Pseudomonas syringae growth. Therefore, bak1/elg-D promotes
      Arabidopsis growth by stimulating BR signaling at the expense of its readiness to
      respond to biotic stress factors. The BAK1/ELG BR co-receptor thus plays an
      important role in BR signaling that is mediated by its LRR domain.

PMID- 22961664
TI  - MusaSAP1, a A20/AN1 zinc finger gene from banana functions as a positive
      regulator in different stress responses.
AB  - A20/AN1 zinc finger domain containing Stress Associated Proteins (SAP) are
      involved in diverse stress response pathways in plants. In the present study, a
      novel banana SAP gene, MusaSAP1, was identified from banana EST database and was
      subsequently characterized by overexpression in transgenic banana plants.
      Expression profiling in native banana plants showed that MusaSAP1 was up
      regulated by drought, salt, cold, heat and oxidative stress as well as by
      treatment with abscisic acid. Cellular localization assay carried out by making a
      MusaSAP1::GFP fusion protein indicated that MusaSAP1 is incompletely translocated
      to nucleus. Copy number analysis performed using real time PCR and Southern
      blotting indicated that MusaSAP1 occurs in the banana genome in a single copy per
      11 chromosome set. Transgenic banana plants constitutively overexpressing
      MusaSAP1 displayed better stress endurance characteristics as compared to
      controls in both in vitro and ex vivo assays. Lesser membrane damage as indicated
      by reduced malondialdehyde levels in transgenic leaves subjected to drought, salt
      or oxidative stress pointed towards significant role for MusaSAP1 in stress
      amelioration pathways of banana. Strong up-regulation of a polyphenol oxidase
      (PPO) coding transcript in MusaSAP1 overexpressing plants together with induction
      of MusaSAP1 by wounding and methyl jasmonate treatment indicated possible
      involvement of MusaSAP1 in biotic stress responses where PPOs perform major
      functions in multiple defense pathways.

PMID- 22961665
TI  - Bio-based nanoemulsion formulation, characterization and antibacterial activity
      against food-borne pathogens.
AB  - The current study deals with the formulation and characterization of bio-based
      oil in water nanoemulsion and its potential antibacterial activity. A typical
      v/v% of eucalyptus oil (16.66%), Tween 80 (16.66%), and water (68.68%) was
      prepared by ultrasonication method. The mean droplet size was 17.1 nm as
      confirmed by dynamic light scattering. Different concentrations of the
      formulation ranging from undiluted to 10-, 100-, and 1000-fold dilutions were
      used to check the antibacterial activity in three different microorganisms,
      namely, Bacillus cereus, Staphylococcus aureus (Gram-positive), and Escherichia
      coli (Gram-negative). All three species showed a 100% bactericidal at the 10-fold
      dilution of the nanoemulsion formulation in the following order: B. cereus at 0th
      min, S. aureus at 15 min and E. coli at 1 h, respectively. A 10-fold dilution of
      the nanoemulsion showed that, the cytoplasmic content leakage from the bacterial
      species was high for S. aureus when compared to B. cereus and E. coli as
      determined by UV-Vis spectroscopic method. Fluorescence microscopic technique
      further confirmed this study.

PMID- 22961666
TI  - Proteomic profiling identifies dysregulated pathways in small cell lung cancer
      and novel therapeutic targets including PARP1.
AB  - Small cell lung cancer (SCLC) is an aggressive malignancy distinct from non-small
      cell lung cancer (NSCLC) in its metastatic potential and treatment response.
      Using an integrative proteomic and transcriptomic analysis, we investigated
      molecular differences contributing to the distinct clinical behavior of SCLCs and
      NSCLCs. SCLCs showed lower levels of several receptor tyrosine kinases and
      decreased activation of phosphoinositide 3-kinase (PI3K) and Ras/mitogen
      activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)
      pathways but significantly increased levels of E2F1-regulated factors including
      enhancer of zeste homolog 2 (EZH2), thymidylate synthase, apoptosis mediators,
      and DNA repair proteins. In addition, PARP1, a DNA repair protein and E2F1 co
      activator, was highly expressed at the mRNA and protein levels in SCLCs. SCLC
      growth was inhibited by PARP1 and EZH2 knockdown. Furthermore, SCLC was
      significantly more sensitive to PARP inhibitors than were NSCLCs, and PARP
      inhibition downregulated key components of the DNA repair machinery and enhanced
      the efficacy of chemotherapy. SIGNIFICANCE: SCLC is a highly lethal cancer with a
      5-year survival rate of less than 10%. To date, no molecularly targeted agents
      have prolonged survival in patients with SCLCs. As a step toward identifying new
      targets, we systematically profiled SCLCs with a focus on therapeutically
      relevant signaling pathways. Our data reveal fundamental differences in the
      patterns of pathway activation in SCLCs and NSCLCs and identify several potential
      therapeutic targets for SCLCs, including PARP1 and EZH2. On the basis of these
      results, clinical studies evaluating PARP and EZH2 inhibition, together with
      chemotherapy or other agents, warrant further investigation.

PMID- 22961669
TI  - Concise review: Patient-derived olfactory stem cells: new models for brain
      diseases.
AB  - Traditional models of brain diseases have had limited success in driving
      candidate drugs into successful clinical translation. This has resulted in large
      international pharmaceutical companies moving out of neuroscience research. Cells
      are not brains, obviously, but new patient-derived stem models have the potential
      to elucidate cell biological aspects of brain diseases that are not present in
      worm, fly, or rodent models, the work horses of disease investigations and drug
      discovery. Neural stem cells are present in the olfactory mucosa, the organ of
      smell in the nose. Patient-derived olfactory mucosa has demonstrated disease
      associated differences in a variety of brain diseases and recently olfactory
      mucosa stem cells have been generated from patients with schizophrenia,
      Parkinson's disease, and familial dysautonomia. By comparison with cells from
      healthy controls, patient-derived olfactory mucosa stem cells show disease
      specific alterations in gene expression and cell functions including: a shorter
      cell cycle and faster proliferation in schizophrenia, oxidative stress in
      Parkinson's disease, and altered cell migration in familial dysautonomia.
      Olfactory stem cell cultures thus reveal patient-control differences, even in
      complex genetic diseases such as schizophrenia and Parkinson's disease,
      indicating that multiple genes of small effect can converge on shared cell
      signaling pathways to present as a disease-specific cellular phenotype. Olfactory
      mucosa stem cells can be maintained in homogeneous cultures that allow robust and
      repeatable multiwell assays suitable for screening libraries of drug candidate
      molecules.

PMID- 22961667
TI  - Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors.
AB  - The clinical efficacy of epidermal growth factor receptor (EGFR) kinase
      inhibitors is limited by the development of drug resistance. The irreversible
      EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of
      drug resistance mediated by the EGFR T790M mutation. Here, we show, in multiple
      complementary models, that resistance to WZ4002 develops through aberrant
      activation of extracellular signal-regulated kinase (ERK) signaling caused by
      either an amplification of mitogen-activated protein kinase 1 (MAPK1) or by
      downregulation of negative regulators of ERK signaling. Inhibition of MAP-ERK
      kinase (MEK) or ERK restores sensitivity to WZ4002 and prevents the emergence of
      drug resistance. We further identify MAPK1 amplification in an erlotinib
      resistant EGFR-mutant non-small cell lung carcinoma patient. In addition, the
      WZ4002-resistant MAPK1-amplified cells also show an increase both in EGFR
      internalization and a decrease in sensitivity to cytotoxic chemotherapy. Our
      findings provide insights into mechanisms of drug resistance to EGFR kinase
      inhibitors and highlight rational combination therapies that should be evaluated
      in clinical trials.

PMID- 22961668
TI  - Over-expression of circadian clock gene Bmal1 affects proliferation and the
      canonical Wnt pathway in NIH-3T3 cells.
AB  - Bmal1 is a transcription factor that plays a central role in the regulation of
      circadian rhythms. Recent study reported that Bmal1-/- mice displayed many known
      features of premature ageing, such as reduction of bone mass. Our previous study
      has found that both the proliferation of bone marrow mesenchymal stem cells
      (BMSCs) and Bmal1 expression decreased with advancing age. It seemed that a
      positive correlation existed between Bmal1 protein level and the proliferative
      activity of BMSCs. beta-catenin, the core factor of the canonical Wnt pathway,
      also showed reduced expression in aged mice. In order to further confirm this, we
      constructed a lentiviral vector to over-express Bmal1 in NIH-3T3 cells;
      successful transfection was verified. The cell proliferation rate of infected
      cells was higher than the non-transfected NIH-3T3 cells, suggesting that
      circadian clock gene Bmal1 can promote proliferation. beta-catenin showed an
      increased expression in NIH-3T3 cells after Bmal1 over-expression, indicating
      that activation of the canonical Wnt pathway might be the mechanism underlying
      the effect of circadian clock gene Bmal on promoting cell proliferation.

PMID- 22961670
TI  - Generation of osteogenic construct using periosteal-derived osteoblasts and
      polydioxanone/pluronic F127 scaffold with periosteal-derived CD146 positive
      endothelial-like cells.
AB  - The purpose of this study was to generate tissue-engineered bone using human
      periosteal-derived osteoblasts (PO) and polydioxanone/pluronic F127 (PDO/pluronic
      F127) scaffold with preseeded human periosteal-derived CD146 positive endothelial
      like cells (PE). PE were purified from the periosteal cell population by cell
      sorting. One of the important factors to consider in generating tissue-engineered
      bone using osteoprecursor and endothelial cells and a specific scaffold is
      whether the function of osteoprecursor and endothelial cells can be maintained in
      originally different culture medium conditions. After human PE were preseeded
      into PDO/pluronic F127 scaffold and cultured in endothelial cell basal medium-2
      for 7 days, human PO were seeded into the PDO/pluronic F127 scaffold with PE, and
      then, this cell-scaffold construct was cultured in endothelial cell basal medium
      2 with osteogenic induction factors, including ascorbic acid, dexamethasone, and
      beta-glycerophosphate, for a further 7 days. Then, this 2-week cultured construct
      was grafted into the mandibular defect of miniature pig. Twelve weeks after
      implantation, the animal was sacrificed. Clinical examination revealed that newly
      formed bone was seen more clearly in the defect with human PO and PDO/pluronic
      F127 scaffold with preseeded human PE. The experimental results suggest that
      tissue-engineered bone formation using human PO and PDO/pluronic F127 scaffold
      with preseeded human PE can be used to restore skeletal integrity to various bony
      defects when used in clinics.

PMID- 22961671
TI  - Evaluating the prognostic value of positron-emission tomography myocardial
      perfusion imaging using automated software to calculate perfusion defect size.
AB  - BACKGROUND: Myocardial perfusion imaging by positron-emission tomography (PET
      MPI) is regarded as a valid technique for the diagnosis of coronary artery
      disease (CAD), but the incremental prognostic value of PET MPI among individuals
      with known or suspected CAD is not firmly established. HYPOTHESIS: Myocardial
      perfusion defect sizes as measured by PET MPI using automated software will
      provide incremental prognostic value for cardiac and all-cause mortality.
      METHODS: This study included 3739 individuals who underwent rest-stress rubidium
      82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress
      induced myocardial perfusion defect sizes were determined objectively by
      automated computer software. Study participants were followed for a mean of 5.2
      years for cardiac and all-cause mortality. Cox proportional hazards models were
      developed to evaluate the incremental prognostic value of PET MPI. RESULTS: A
      strong correlation was observed between perfusion defect sizes assessed visually
      and by automated software (r = 0.76). After adjusting for cardiac risk factors,
      known CAD, noncoronary vascular disease, and use of cardioprotective medications,
      stress perfusion defect size was strongly associated with cardiac death (P <
      0.001). Rest perfusion defects demonstrated a stronger association with cardiac
      death (P < 0.001) than stress-induced perfusion defects (P = 0.01), yet both were
      highly significant. Similar patterns held for all-cause death. CONCLUSIONS: The
      current study is the largest to date demonstrating PET MPI provides incremental
      prognostic value among individuals with known or suspected CAD. Automated
      calculation of perfusion defect sizes may provide valuable supplementary
      information to visual assessment.

PMID- 22961672
TI  - "IH8U": confronting cyberbullying and exploring the use of cybertools in teen
      dating relationships.
AB  - Cyberbullying among adolescents has been a major focus of attention in mainstream
      media and has been documented to have many negative effects, as evidenced by
      several highly publicized suicides of teens who had been bullied online. The
      growing body of research about cyberbullying has rarely considered, however, the
      practice of cyberbullying between intimate partners. This article focuses on the
      frequency, types, and effect of cyberbullying between intimate partners in teen
      dating relationships. I examine the use of cybertools (electronic forms of
      communication) as mechanisms of power and control in relationships for both the
      target and the perpetrator. Suggested methods of prevention and intervention for
      adults working with teens who are experiencing cyberbullying in dating
      relationships are discussed.

PMID- 22961673
TI  - Acute kidney injury due to intravenous bleach injection.
AB  - INTRODUCTION: Sodium hypochlorite is the active ingredient in bleach, a
      ubiquitous household disinfectant, and has known toxicities depending on route of
      exposure and amount. Acute kidney injury due to sodium hypochlorite exposure has
      never been reported. Patients that did develop nephrotoxicity following bleach
      exposure did so due to development of other risk factors for kidney injury such
      as volume depletion or sepsis. DISCUSSION: We report a patient who presented with
      black urine after parenteral self-administration of a large quantity of bleach.
      We review the clinical presentation, laboratory and biopsy findings, and outcome
      as well as discuss possible mechanisms of sodium hypochlorite toxicity and
      management strategies.

PMID- 22961674
TI  - An assessment of fluorescence- and absorbance-based assays to study metal-oxide
      nanoparticle ROS production and effects on bacterial membranes.
AB  - The production and inevitable release of engineered nanoparticles requires rapid
      approaches to screen for their potential effects in environmental organisms,
      including bacteria. In bacteria, engineered nanoparticle effects can initiate at
      the cell membrane, for example by structurally damaging membranes or inhibiting
      energy transduction. Commercially available fluorescence- and absorbance-based
      assays could allow for rapidly assaying engineered nanoparticle effects on
      bacterial membranes, but there are limitations, including that: 1) assays are not
      currently configured to operate as part of a comprehensive high-throughput
      screening system, since assay conditions vary widely and formats are mostly high
      volume and thus low-throughput, and; 2) engineered nanoparticles can interfere
      with assay reagents or function, yielding false-negative or -positive outcomes.
      Here, key assays to study reactive oxygen species (total ROS, and superoxide)
      production, and impacts on bacterial membrane integrity, membrane potential, and
      electron transport chain activity, are assessed for their potential use as a
      comprehensive system to test for nanoparticle effects in bacteria. To address
      (1), assays are adapted for simultaneous use in 96-well microplates under
      harmonized conditions. To address (2), a general scheme to test for engineered
      nanoparticle interferences with assay reagents and function is conceived, and
      used to study assay interferences by three nanoscale metal-oxides: nano-TiO2 ,
      nano-CeO2 , and nano-ZnO. The results show that the selected assays can be used
      as a suite, and that nanoparticle interferences, when they occur, can be
      systematically investigated and often accounted for.

PMID- 22961675
TI  - Measurement of aluminum-carbon distances using S-RESPDOR NMR experiments.
AB  - It is demonstrated that reliable aluminum-carbon distances can be measured in
      samples with (13)C natural abundance by NMR spectroscopy. Overcoupled resonators,
      with only one radio-frequency synthesizer and one amplifier, are used to
      irradiate in the same pulse sequence (27)Al and (13)C nuclei, which differ by
      only 3.6 % in Larmor frequencies. The combination of (27)Al saturation pulse with
      heteronuclear dipolar recoupling yields dipolar dephasing of the (13)C signal,
      which only depends on the Al-C distance and the efficiency of the saturation
      pulse. Therefore, reliable distances can be obtained by rapid fitting of
      experimental data to an analytical expression. It is demonstrated that with
      natural isotopic abundance this approach allows recovery of Al-C distances of 216
      pm for the covalent bond in lithium tetraalkyl aluminates, commonly used as a co
      catalyst in olefin polymerization processes, and which range from 274 to 381 pm
      for the three carbon atoms in aluminum lactate. The accuracy of the measured
      internuclear distances is carefully estimated.

PMID- 22961676
TI  - A facile band alignment of polymeric carbon nitride semiconductors to construct
      isotype heterojunctions.

PMID- 22961677
TI  - Risk of ischaemic heart disease in patients with inflammatory bowel disease: a
      nationwide Danish cohort study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder.
      Systemic inflammation increases the risk of atherosclerosis and ischaemic heart
      disease (IHD). OBJECTIVE: To examine the impact of IBD, including its duration
      and treatment, on the risk of IHD. METHODS: In a nationwide population-based
      cohort of 4.6 million Danes aged >= 15 years, we compared people diagnosed with
      IBD during 1997-2009 (n=28 833) with IBD-free individuals. Subjects with IHD were
      identified in the National Patient Register. Using Poisson regression, we
      estimated the incidence rate ratios (IRRs) for IHD with 95% CI with adjustment
      for age, gender, socioeconomic status, calendar year and use of drugs for
      comorbidities. RESULTS: A markedly increased risk of IHD was seen within the
      first year after IBD diagnosis (IRR=2.13 95% CI 1.91 to 2.38). During 1-13 years
      of follow-up after IBD diagnosis, the risk of IHD was 1.22 (95% CI 1.14 to 1.30).
      The risk of IHD was lower among patients with IBD using 5-aminosalicylic acids
      (IRR=1.16; 95% CI 1.06 to 1.26) than among non-users (IRR=1.36; 95% CI 1.22 to
      1.51) (p=0.02), in particular among oral corticosteroid users, used as a proxy
      for disease severity. Likewise patients treated surgically or with thiopurines
      and tumour necrosis factor alpha antagonists tended to have reduced IRRs for IHD.
      CONCLUSIONS: The risk of IHD was highest in the first year after IBD diagnosis,
      possibly owing to ascertainment bias. The increased long-term risk of IHD in IBD
      may be related to chronic inflammation, and interventions reducing the
      inflammatory burden may attenuate this risk.

PMID- 22961678
TI  - Does Helicobacter pylori eradication really reduce the risk of gastric cancer at
      the population level?

PMID- 22961679
TI  - Acceleration in colorectal carcinogenesis: the hare, the tortoise or myth?

PMID- 22961680
TI  - Pharmacokinetics, bioavailability, tissue distribution, excretion, and metabolite
      identification of methoxyflavones in Kaempferia parviflora extract in rats.
AB  - Kaempferia parviflora (KP) is an herbal plant in the family of Zingiberaceae. KP
      mainly contains methoxyflavones, especially 5,7-dimethoxyflavone (DMF), 5,7,4'
      trimethoxyflavone (TMF), and 3,5,7,3',4'-pentamethoxyflavone (PMF). The present
      study was designed to characterize the pharmacokinetics, including
      bioavailability, distribution, excretion, and identification of metabolites after
      administration of a KP ethanolic extract. Male rats were orally or intravenously
      administered a 250 mg/kg concentration of a KP extract, and blood samples were
      obtained at selected times to determine pharmacokinetic parameters of PMF, TMF,
      and DMF. For distribution and excretion studies, the organs, urine, and feces
      samples were collected at various times after oral administration of a larger
      (750 mg/kg) dose of KP extract. Methoxyflavones in the biological samples were
      quantified by high-performance liquid chromatography-UV, and the metabolites in
      urine and feces were further identified by using liquid chromatography-tandem
      mass spectrometry. After oral administration, concentrations of the three
      methoxyflavones quickly approached their maximal concentration, ranging from 0.55
      to 0.88 MUg/ml within 1 to 2 h after administration, and then were gradually
      excreted with half-lives of 3 to 6 h. The methoxyflavones showed low oral
      bioavailability of 1 to 4%. Three methoxyflavones were detected at their highest
      levels in liver followed by kidney. They were also found in lung, testes, and
      brain. After absorption, organ distribution, and metabolism, the components of KP
      were mainly eliminated through urine in the forms of demethylated, sulfated, and
      glucuronidated products and as demethylated metabolites in the feces. The parent
      compounds were found to have 0.79, 1.76, and 3.10% dose recovery in urine and
      1.06, 1.77, and 0.96% dose recovery in feces for PMF, TMF, and DMF, respectively.
      These studies are the first to describe the pharmacokinetics of KP extract to
      provide the information on blood and tissue levels.

PMID- 22961681
TI  - Mitigating the inhibition of human bile salt export pump by drugs: opportunities
      provided by physicochemical property modulation, in silico modeling, and
      structural modification.
AB  - The human bile salt export pump (BSEP) is a membrane protein expressed on the
      canalicular plasma membrane domain of hepatocytes, which mediates active
      transport of unconjugated and conjugated bile salts from liver cells into bile.
      BSEP activity therefore plays an important role in bile flow. In humans,
      genetically inherited defects in BSEP expression or activity cause cholestatic
      liver injury, and many drugs that cause cholestatic drug-induced liver injury
      (DILI) in humans have been shown to inhibit BSEP activity in vitro and in vivo.
      These findings suggest that inhibition of BSEP activity by drugs could be one of
      the mechanisms that initiate human DILI. To gain insight into the chemical
      features responsible for BSEP inhibition, we have used a recently described in
      vitro membrane vesicle BSEP inhibition assay to quantify transporter inhibition
      for a set of 624 compounds. The relationship between BSEP inhibition and
      molecular physicochemical properties was investigated, and our results show that
      lipophilicity and molecular size are significantly correlated with BSEP
      inhibition. This data set was further used to build predictive BSEP
      classification models through multiple quantitative structure-activity
      relationship modeling approaches. The highest level of predictive accuracy was
      provided by a support vector machine model (accuracy = 0.87, kappa = 0.74). These
      analyses highlight the potential value that can be gained by combining
      computational methods with experimental efforts in early stages of drug discovery
      projects to minimize the propensity of drug candidates to inhibit BSEP.

PMID- 22961682
TI  - Disposition and metabolism of LY2452473, a selective androgen receptor modulator,
      in humans.
AB  - The disposition and metabolism of isopropyl N-[(2S)-7-cyano-4-(2-pyridylmethyl)
      2,3-dihydro-1H-cyclopenta[b]indol-2-yl]carbamate (LY2452473; a selective androgen
      receptor modulator) in humans was characterized after a single 15-mg (100 MUCi)
      oral dose of [14C]LY2452473 to six healthy male subjects. LY2452473 was absorbed
      rapidly (time to reach maximum plasma concentration for both LY2452473 and total
      radioactivity was 2-3 h) and cleared slowly (plasma terminal t(1/2) of 27 h for
      LY2452473 and 51 h for the total radioactivity). LY2452473 and metabolites S5
      (acetylamine) and S12 (hydroxylation on the cyclopentene) were major circulating
      entities in plasma, accounting for approximately 42, 21, and 35% of the total
      radioactivity exposure, respectively, as calculated from relative area under the
      concentration versus time curves from zero to 48 h derived from the plasma
      radiochromatograms. The radioactive dose was almost completely recovered after
      312 h with 47.9% of the dose eliminated in urine and 46.6% in feces. Minimal
      LY2452473 was detected in excreta, indicating that metabolic clearance was the
      main route of elimination. Multiple metabolic pathways were observed with no
      single metabolic pathway accounting for more than 30% of the dose in excreta.
      Metabolite S10 (a diol across the cyclopenta-indole linkage) was the largest
      excretory metabolite (approximately 14% of the dose). S10 displayed interesting
      chemical and chromatographic properties, undergoing conversion to the
      corresponding epoxide under acidic conditions and conversion back to the diol
      under neutral conditions. An in vitro phenotyping approach indicated that CYP3A4
      was the largest contributor to LY2452473 depletion.

PMID- 22961683
TI  - Centimeter-sized dried foam films of graphene: preparation, mechanical and
      electronic properties.
AB  - A simple method to fabricate centimeter-sized thin films of graphene oxide (GO)
      is developed via drying the relative liquid film supported by a rigid frame.
      After reduction, centimeter-sized thin reduced GO films are obtained, and the
      maximum transparency is 75.8% while the minimum sheet resistance is 920 Omega ?(
      1) .

PMID- 22961684
TI  - Comment about intestinal gluconeogenesis after gastric bypass in human in
      relation with the paper by Hayes et al., Obes. Surg. 2011.

PMID- 22961685
TI  - Psychiatric predictors of surgery non-completion following suitability assessment
      for bariatric surgery.
AB  - BACKGROUND: Bariatric surgery is recognized as a treatment for severe obesity;
      however, little is known about factors influencing patient surgery non
      completion. This study explored the relationship between psychiatric factors and
      patient non-completion during the pre-bariatric surgery suitability assessment.
      METHODS: A total of 367 individuals underwent a structured psychiatric interview
      and were classified as either surgery completers (SC) or surgery non-completers
      (SNC) if they attended at least one pre-surgery assessment appointment but did
      not receive surgery. RESULTS: The results showed that in comparison to the SC
      group, the SNC group had significantly higher rates of overall past Axis I
      psychiatric disorders (58.1 vs. 46.6 %, p = 0.035), past anxiety disorders (17.4
      vs. 9.4 %, p = 0.03), and past substance use disorders (8.7 vs. 3.7 %, p = 0.03).
      For specific past psychiatric disorders, the SNC group exhibited significantly
      higher rates of a past post-traumatic stress disorder (PTSD) (5 vs. 1 %, p =
      0.029) and past substance dependence disorder (7 vs. 1 %, p = 0.005). Although
      overall current psychiatric disorders did not significantly differ between
      groups, the SNC group had significantly higher rates of current PTSD (2 vs. 0 %,
      p = 0.049) and current generalized anxiety disorder (4 vs. 0 %, p = 0.005).
      CONCLUSIONS: A past history of an anxiety or substance use disorder may play a
      role in patients not completing the assessment component of the bariatric surgery
      process. Additional psychosocial support, such as cognitive behavioral therapy or
      targeted psychoeducation, may help improve patient completion of the pre-surgery
      assessment phase.

PMID- 22961686
TI  - Unequivocal 13C NMR assignment of cyclohexadienyl rings in bromotyrosine-derived
      metabolites from marine sponges.
AB  - Bromotyrosine-derived compounds are commonly isolated from Verongida sponges and
      are a major class of marine natural products. Here we report on the unequivocal
      (13)C NMR assignment of the brominated carbons at positions C-2 and C-4 of the
      cyclohexadiene ring, two carbons whose resonances are often incorrectly assigned.
      Interpretation of HMBC data acquired for a series of known bromotyrosine
      analogues, which included ianthesine E(1), aerothionin (2), 11-hydroxyaerothionin
      (3), and 11,19-dideoxyfistularin-3 (4), allowed us to unequivocally assign the
      carbons in question, C-2 and C-4, through the observance of unique HMBC
      correlations from the C-1 hydroxyl proton. Here we present the complete 2D NMR
      data sets recorded in DMSO-d(6) for 2-4 that were used to confirm the assignment
      and establish the working model. Using this model, a survey of the literature
      revealed that many members of this structure class had been wrongly assigned.
      This paper serves to reassign those compounds whose (13)C NMR assignment at
      positions C-2 and C-4 of the cyclohexadiene ring should be reversed.

PMID- 22961687
TI  - Imaging the efficacy of UVC irradiation on superficial brain tumors and
      metastasis in live mice at the subcellular level.
AB  - The effect of UVC irradiation was investigated on a model of brain cancer and a
      model of experimental brain metastasis. For the brain cancer model, brain cancer
      cells were injected stereotactically into the brain. For the brain metastasis
      model, lung cancer cells were injected intra-carotidally or stereotactically. The
      U87 human glioma cell line was used for the brain cancer model, and the Lewis
      lung carcinoma (LLC) was used for the experimental brain metastasis model. Both
      cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm.
      A craniotomy open window was used to image single cancer cells in the brain. This
      double labeling of the cancer cells with GFP and RFP enabled apoptosis of single
      cells to be imaged at the subcellular level through the craniotomy open window.
      UVC irradiation, beamed through the craniotomy open window, induced apoptosis in
      the cancer cells. UVC irradiation was effective on LLC and significantly extended
      survival of the mice with experimental brain metastasis. In contrast, the U87
      glioma was relatively resistant to UVC irradiation. The results of this study
      suggest the use of UVC for treatment of superficial brain cancer or metastasis.

PMID- 22961688
TI  - Reduced hepatic stellate cell expression of Kruppel-like factor 6 tumor
      suppressor isoforms amplifies fibrosis during acute and chronic rodent liver
      injury.
AB  - Kruppel-like factor 6 (KLF6), a zinc finger transcription factor and tumor
      suppressor, is induced as an immediate-early gene during hepatic stellate cell
      (HSC) activation. The paradoxical induction of a tumor suppressor in HSCs during
      proliferation led us to explore the biology of wildtype KLF6 (KLF6(WT) ) and its
      antagonistic, alternatively spliced isoform KLF6(SV1) in cultured HSCs and animal
      models. The animal models generated include a global heterozygous KLF6 mouse
      (Klf6+/-), and transgenic mice expressing either hKLF6(WT) or hKLF6(SV1) under
      the control of the Collagen alpha2 (I) promoter to drive HSC-specific gene
      expression following injury. The rat Klf6 transcript has multiple splice forms
      that are homologous to those of the human KLF6 gene. Following a transient
      increase, all rat Klf6 isoforms decreased in response to acute carbon
      tetrachloride (CCl(4)) liver injury and culture-induced activation. After acute
      CCl(4), Klf6+/- mice developed significantly increased fibrosis and enhanced
      fibrogenic messenger RNA (mRNA) and protein expression. In contrast, HSC-specific
      transgenic mice overexpressing KLF6(WT) or KLF6(SV1) developed significantly
      diminished fibrosis with reduced expression of fibrogenic genes. Chromatin IP and
      quantitative reverse-transcription polymerase chain reaction in mouse HSCs
      overexpressing KLF6(WT) demonstrated KLF6(WT) binding to GC boxes in promoters of
      Colalpha1 (I), Colalpha2 (I), and beta-platelet-derived growth factor receptor
      (beta-Pdgfr) with reduced gene expression, consistent with transcriptional
      repression by KLF6. Stellate cells overexpressing either KLF6(WT) or KLF6(SV1)
      were more susceptible to apoptotic stress based on poly (ADP-ribose) polymerase
      (PARP) cleavage. CONCLUSION: KLF6 reduces fibrogenic activity of HSCs by way of
      two distinct mechanisms, direct transcriptional repression of target fibrogenic
      genes and increased apoptosis of activated HSCs. These results suggest that
      following its initial induction, sustained down-regulation of KLF6 in liver
      injury may allow de-repression of fibrogenic genes and decreased stellate cell
      clearance by inhibiting apoptosis.

PMID- 22961689
TI  - Comparison of the effects of pelargonic acid vanillylamide and capsaicin on human
      vanilloid receptors.
AB  - Pelargonic acid vanillylamide is like capsaicin a natural capsaicinoid from chili
      peppers and commonly used in food additives to create a hot sensation, even in
      self-defense pepper sprays and as an alternative to capsaicin in medical products
      for topical treatment of pain. Although the chemical structures of both compounds
      are similar, preclinical data suggest that capsaicin is the more potent compound.
      We therefore performed voltage-clamp recordings using cells transfected with the
      human vanilloid receptor TRPV1 in order to assess the responses of pelargonic
      acid vanillylamide and capsaicin at the receptor level. We provide evidence that
      at the molecular target TRPV1, the concentration-response curves, kinetics of
      current activation, as well as inhibition by the competitive antagonist
      capsazepine were not significantly different between the two capsaicinoids. We
      suggest that the different effects of the two capsaicinoids observed in previous
      studies may rather be due to different physicochemical or pharmacokinetic
      properties than to different pharmacological profiles at the receptor level.

PMID- 22961690
TI  - Phase I trial and pharmacokinetic study of sorafenib in children with
      neurofibromatosis type I and plexiform neurofibromas.
AB  - BACKGROUND: Sorafenib targets multiple pathways thought to be crucial in growth
      of plexiform neurofibroma (PN) in children with neurofibromatosis type 1 (NF1).
      Sorafenib has been tolerated with manageable toxicities in adults and children
      with refractory cancer. We conducted a separate study in this population.
      Monitoring long-term toxicities such as effects on growth and obtaining
      additional pharmacokinetic data were of importance due to the young age and long
      duration of therapy seen in previous phase I trials in children with NF1.
      PROCEDURE: Children >=3 and <=18-year-old with NF1 and inoperable PN were
      eligible. Sorafenib was administered orally twice daily for consecutive 28-day
      cycles. Maximum tolerated dose (MTD) was determined from toxicities observed
      during the first three cycles. RESULTS: Nine children enrolled, median age 8 (6
      12) years. At the starting 115 mg/m(2) /dose (n = 5), two experienced dose
      limiting grade 3 pain in their PN. At the de-escalated 80 mg/m(2) /dose (n = 4),
      approximately 40% of the pediatric solid tumor MTD, two had dose-limiting
      toxicity (grade 3 rash and grade 4 mood alteration), exceeding the MTD. At 80
      mg/m(2) /dose, the median AUC(0-12 hours) at steady-state was 39.5 ug hours/ml.
      Toxicities appeared to correspond with decreases in quality of life (QOL). No
      tumor shrinkage was observed. CONCLUSIONS: Children with NF1 and PN did not
      tolerate sorafenib at doses substantially lower than the MTD in children and
      adults with malignant solid tumors. Future trials with targeted agents for
      children with NF1 may require a more conservative starting dose and separate
      definitions of dose limiting toxicities (DLT) than children with cancer.

PMID- 22961691
TI  - Genetic diversity and mating types of Fusarium culmorum and Fusarium graminearum
      originating from different agro-ecological regions in Turkey.
AB  - Fusarium culmorum and F. graminearum are the major pathogens for dryland
      root/foot-rot and head-blight diseases in economically important grain crops.
      This study was aimed at the molecular characterization of Fusarium spp. isolates,
      which have been collected from cereal fields in three agro-ecological regions in
      Turkey. Genetic diversity has been analyzed by generating RFLP markers from the
      intergenic spacer (IGS) region of ribosomal RNA. The selection of restriction
      enzymes for IGS-RFLP studies has been found critical to maximize polymorphic
      markers. Only 3 of 14 restriction endonucleases were useful in differentiating
      Fusarium spp. isolates. PstI was the most efficient enzyme to produce a maximum
      of nine DNA markers in one individual and total 22 polymorphic representative
      banding patterns. Polymorphism based on IGS-RFLP was high and average 88% in both
      species. There was no association between IGS diversity and geographic locations
      from which the samples were taken. Both MAT-1 and MAT-2 sequences were amplified
      in F. graminearum similarly to previous reports. Most of the F. culmorum isolates
      carried either MAT-1 or MAT-2 sequences, and differently two isolates carried
      both sequences. Mating type determination was helpful to distinguish F.
      pseudograminearum from F. graminearum, which cannot be discriminated by SCAR
      markers or morphological assessment. High genetic diversity by IGS-RFLP markers
      in F. culmorum was discussed in relation to its fitness as the most common
      pathogen in dryland root rot complex (DLRRC). 

PMID- 22961692
TI  - Detection of low level cryoglobulins by flow cytometry.
AB  - Several patients with cryoglobulin (CG) associated symptoms are seronegative for
      CG and other potentially causative biomarkers. We analyzed whether it is possible
      to detect cryoprecipitates by flow cytometry and whether the sensitivity of their
      demonstration can be increased as compared to visual inspection. Sera from 91
      patients with suspected CG associated symptoms and 33 healthy controls were
      examined for the presence of CG by conventional visual testing and by flow
      cytometry for small diffracting particles. For calibration purposes we tested
      lipid micelle dilutions (positive controls) by both methods. The minimum
      concentrations of lipid micelles to be detected by visual inspection and flow
      cytometry were 128.5 and 2.0 pg ml(-1), respectively. Among the 91 patients and
      33 controls, only 1 patient serum was positive for CG by conventional testing.
      This sample was also positive on flow cytometry. In the serum of a patient known
      to be positive for CG, laser diffracting particles were quantified by flow
      cytometry after keeping serum at 4 degrees C for 3 days. Of the 91 patients, 14
      additional samples displayed cold precipitates which redissolved after rewarming
      during flow cytometry. All 15 (1 + 14) patients positive for CG on flow cytometry
      suffered from symptoms usually associated with CG. Some precipitates were labeled
      with anti IgG and IgM antibodies confirming that the particles detected by flow
      cytometry contained immunoglobulins. No small diffracting particles were detected
      in the sera of the 33 healthy controls. Flow cytometry is equally specific but
      much more sensitive in the detection of CG than visual inspection.

PMID- 22961693
TI  - Recommended levels of physical activity to avoid adiposity in Spanish children.
AB  - What is already known about this subject There is an association between
      adiposity levels and physical activity guidelines for adolescents. Achieving
      physical activity recommendations helps adolescents to prevent obesity status.
      What this study adds This paper presents an association between physical activity
      levels and obesity status. This paper supports physical activity recommendations
      to avoid children's obesity levels. This paper emphasizes vigorous physical
      activity for this matter. BACKGROUND: There is no information about physical
      activity (PA) recommendations to avoid children's obesity levels and how much of
      vigorous PA (VPA) is included into the '60 minutes of MVPA 5 days a week'
      recommendation for children. OBJECTIVE: The aim of this study was to examine the
      association between PA and adiposity in children and to examine whether the
      current PA guidelines are associated with a low risk of having excess of body fat
      in children, with special focus on sex differences, and PA intensity. METHODS: A
      sample of 439 Spanish children aged 8-10 years from the European Youth Heart
      Study participated in the study. The variables measured were anthropometric
      characteristics (height, weight, body mass index [BMI], skin-folds and waist
      circumference) and PA was measured during 6 consecutive days using the GT1M
      accelerometer. RESULTS: Receiver operating characteristic analysis showed
      significant cut-off points associated with non-overweight: 45 min d(-1) of VPA
      and 67 min d(-1) of moderate-to-vigorous physical activity (MVPA) (using BMI
      categories); and non-fat: 41 min d(-1) of VPA and 67 min d(-1) of MVPA (using
      percentage of body fat) and 38 min d(-1) of VPA and 47 min d(-1) of MVPA (using
      waist circumference categories) for boys. For girls, the optimal cut-offs of
      moderate-to-vigorous activity and MVPA associated with non-overweight were 24 and
      57 min d(-1) , respectively (BMI). Boys who did not meet 67 min in MVPA had an
      increased risk of being overweight + obese and overfat + obese (odds ratio [OR] =
      2.48, 95% confidence interval [CI] = 1.36, 4.53, and OR = 2.56, 95% CI = 1.12,
      5.82). CONCLUSIONS: The findings support current PA recommendations (60 min d(-1)
      of MVPA) to avoid excess of body fat in Spanish children. However, VPA appears to
      be an important component for the prevention of obesity, and our findings suggest
      that PA recommendations should specify the dose of VPA required for optimal
      health. Therefore, public health PA recommendations should incorporate
      specifically a greater dose of VPA into the total amount of MVPA in 8- to 10-year
      old boys.

PMID- 22961694
TI  - A quantitative bioapatite/collagen calibration method using Raman spectroscopy of
      bone.
AB  - Numerous calibration models were developed and tested for the quantitative
      analysis of collagen and bioapatite in bone using Raman spectroscopy. The nu1
      phosphate vibration at 960 cm(-1) was used as indicator of the content of
      bioapatite while for collagen three markers were used: the C-H2 band at 2940 cm(
      1) , the amide I band at 1667 cm(-1) and the vibrations of proline and
      hydroxyproline at 855 and 878 cm(-1) , respectively. Also a calibration model
      based on the PLS algorithm was developed, too. Validation of the derived
      calibration models indicated that the model that makes use of the height ratio of
      the peaks 960/(855+878) exhibits the best accuracy.

PMID- 22961695
TI  - Multiple facets of the DNA damage response contribute to the radioresistance of
      mouse mesenchymal stromal cell lines.
AB  - The regeneration of the hematopoietic system following total body irradiation is
      supported by host-derived mesenchymal stromal cells (MSCs) within the bone
      marrow. The mechanisms used by MSCs to survive radiation doses that are lethal to
      the hematopoietic system are poorly understood. The DNA damage response (DDR)
      represents a cohort of signaling pathways that enable cells to execute biological
      responses to genotoxic stress. Here, we examine the role of the DDR in mediating
      the resistance of MSCs to ionizing radiation (IR) treatment using two authentic
      clonal mouse MSC lines, MS5 and ST2, and primary bulk mouse MSCs. We show that
      multiple DDR mechanisms contribute to the radio-resistance of MSCs: robust DDR
      activation via rapid gamma-H2AX formation, activation of effective S and G(2)/M
      DNA damage checkpoints, and efficient repair of IR-induced DNA double-strand
      breaks. We show that MSCs are intrinsically programmed to maximize survival
      following IR treatment by expressing high levels of key DDR proteins including
      ATM, Chk2, and DNA Ligase IV; high levels of the anti-apoptotic, Bcl-2 and Bcl
      (XL); and low levels of the pro-apoptotic, Bim and Puma. As a result, we
      demonstrate that irradiated mouse MSCs withstand IR-induced genotoxic stress,
      continue to proliferate, and retain their capacity to differentiate long-term
      along mesenchymal-derived lineages. We have shown, for the first time, that the
      DDR plays key roles in mediating the radioresistance of mouse MSCs which may have
      important implications for the study and application of MSCs in allogeneic bone
      marrow transplantation, graft-versus-host disease, and cancer treatment.

PMID- 22961696
TI  - Colorimetric protein sensing using catalytically amplified sensor arrays.
AB  - Catalytically active iron oxide nanoparticles are used as recognition elements
      and signal amplifiers for the array-based colorimetric sensing of proteins.
      Interactions between cationic monolayers on the Fe(3) O(4)  NPs and analyte
      proteins differentially modulates the peroxidase-like activity of Fe(3) O(4) 
      NPs, affording catalytically amplified colorimetric signal patterns that enable
      the detection and identification of proteins at 50 nM.

PMID- 22961698
TI  - Noise variance estimation using image noise cross-correlation model on SEM
      images.
AB  - A number of techniques have been proposed during the last three decades for noise
      variance and signal-to-noise ratio (SNR) estimation in digital images. While some
      methods have shown reliability and accuracy in SNR and noise variance
      estimations, other methods are dependent on the nature of the images and perform
      well on a limited number of image types. In this article, we prove the accuracy
      and the efficiency of the image noise cross-correlation estimation model, vs.
      other existing estimators, when applied to different types of scanning electron
      microscope images.

PMID- 22961697
TI  - The Wnt/beta-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1
      expression in colon cancer.
AB  - High-mobility group A1 (HMGA1) encodes proteins that act as mediators in viral
      integration, modification of chromatin structure, neoplastic transformation and
      metastatic progression. Because HMGA1 is overexpressed in most cancers and has
      transcriptional relationships with several Wnt-responsive genes, we explored the
      involvement of HMGA1 in Wnt/beta-catenin/TCF-4 signalling. In adenomatous
      polyposis coli (APC(Min/+)) mice, we observed significant up-regulation of HMGA1
      mRNA and protein in intestinal tumours when compared with normal intestinal
      mucosa. Conversely, restoration of Wnt signalling by the zinc induction of wild
      type APC resulted in HMGA1 down-regulation in HT-29 cells. Because APC mutations
      are associated with mobilization of the beta-catenin/TCF-4 transcriptional
      complex and subsequent activation of downstream oncogenic targets, we analyzed
      the 5'-flanking sequence of HMGA1 for putative TCF-4 binding elements. We
      identified two regions that specifically bind the beta-catenin/TCF-4 complex in
      vitro and in vivo, identifying HMGA1 as an immediate target of the beta
      catenin/TCF-4 signalling pathway in colon cancer. Collectively, these findings
      strongly implicate Wnt/beta-catenin/TCF-4 signalling in regulating HMGA1 to
      further expand the extensive regulatory network affected by Wnt/beta-catenin/TCF
      4 signalling.

PMID- 22961699
TI  - Children, technology, problems, and preferences.
AB  - Increasingly, young people are using various forms of technology in the service
      of communicating with others, and many have noted the possibility of various dire
      consequences of this phenomenon, including sexting, cyberbullying, online
      harassment, and Internet addiction. In our own survey of over 300 adolescents, we
      found that texting and face-to-face communication were considered the most
      "convenient" forms of communication, while face-to-face communication and phone
      conversations were perceived as most likely to lead to "feeling understood" and
      "feeling intimate." Face-to-face communication and texting were perceived as most
      likely to result in feeling regret for sharing too much information. By choosing
      to communicate through technology, many young people, including our patients, can
      continue to be social and, at the same time, keep a somewhat safer emotional
      distance.

PMID- 22961700
TI  - LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors
      in the world, and the development of new therapeutic targets is needed. Recent
      studies have shown that aerobic glycolysis, also known as the Warburg effect,
      mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A
      (LDHA) which executed the final step of aerobic lactate production has been
      reported to be involved in the tumor progression. However, the function of LDHA
      in ESCC has not been investigated. In this study, it was found that LDHA was up
      regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited
      cell growth and cell migration in vitro as well as tumorigenesis in vivo. With
      regard to the molecular mechanism, silencing the expression of LDHA was related
      to decreased AKT activation and cyclin D1 expression and increased cleavage of
      PARP and caspase 8. Taken together, our findings suggest that LDHA plays an
      important role in the progression of ESCC by modulating cell growth, and LDHA
      might be a potential therapeutic target in ESCC.

PMID- 22961701
TI  - Reversible insertion of platinum into coinage group metal-halogen bonds.

PMID- 22961702
TI  - Emergency neurologic life support: meningitis and encephalitis.
AB  - Bacterial meningitis and viral encephalitis, particularly herpes simplex
      encephalitis (HSE), are severe neurological infections that, if not treated
      promptly and effectively, lead to poor neurological outcome or death. Because
      treatment is more effective if given early, the topic of meningitis and
      encephalitis was chosen as an Emergency Neurological Life Support protocol. This
      protocol provides a practical approach to recognition of and urgent treatment for
      bacterial meningitis and HSE, including imaging and spinal fluid analysis, and
      discusses the choice of empirical treatments until the cause of infection is
      determined. Though uncommon in its full form, the typical clinical triad of
      headache, fever, and neck stiffness should alert the clinical practitioner to the
      syndromes. Early attention to the airway and maintaining normotension is crucial
      in treatment of these patients, as is rapid treatment with anti-infectives and,
      in some cases, corticosteroids.

PMID- 22961704
TI  - Ohno's hypothesis and Muller's paradox: sex chromosome dosage compensation may
      serve collective gene functions.
AB  - Muller found halving gene dosage, as in males with one X chromosome, did not
      affect specific gene function. Why then was dosage "compensated?" This paradox
      was solved by invoking collective gene functions such as self/not self
      discrimination afforded by protein aggregation pressure. This predicts female
      susceptibility to autoimmune disease.

PMID- 22961705
TI  - Probing lymphoma infiltration in spleen of AKR/J mice chronically exposed to
      electromagnetic fields for risk assessment--toward noninvasive modeling.
AB  - Using the AKR/J mouse model, the potential of Raman spectroscopy for monitoring
      lymphoma in predisposed subjects is demonstrated by discriminating lymphoma
      infiltration in spleens; the relevance of different excitation profiles is shown.
      Under green excitation with optimal fluorescence bleaching, stronger DNA bands,
      intensity variations at amide-III and phenylalanine bands, and the behavior of
      the 1606/1639 cm(-1) doublet correlate with tumorigenesis. Under red excitation,
      Raman fingerprints with multivariate models help to discriminate AKR/J-mouse
      histological subtypes: Lymphoblastic lymphoma (LB) is found significantly distant
      from both separated lymphocytic lymphoma (LL) and healthy spleen; this agrees
      with histology since LB has well differentiated large lymphoma cells, while LL,
      with smaller cells similar to normal lymphocytes, usually cannot be discriminated
      from normal tissue without histoimmunoassays.

PMID- 22961706
TI  - The continuing professional development for nurses and allied health
      professionals working within musculoskeletal services: a national UK survey.
AB  - OBJECTIVES: To explore the current UK status of continuing professional
      development (CPD) for nurses and allied health professionals (AHPs) working in
      musculoskeletal (MSK) services in the UK. METHODS: A web-based survey was
      developed and used to collect data from service managers, nurses and AHPs who
      work with people who have MSK conditions, recruited through professional interest
      groups via email and website notices. The questionnaire was designed following
      focus groups and telephone conference calls with managers and AHPs from MSK
      services to ensure content validity. Results were collected online and analysed
      in SPSS PASW 17 using frequency data and chi2 analyses. RESULTS: A total of 354
      responses were analysed. The most frequently reported reason for undertaking CPD
      was to improve patient care. The level of staff experience made no significant
      difference to the CPD activities undertaken. The majority of respondents reported
      that their organization was supportive of CPD activities and in applying new
      knowledge to practice, but lack of funding and having too many other tasks to
      complete at work were the most frequently reported barriers to CPD. Many
      commented about the difficulty in accessing CPD in the face of increasing
      workload pressure and tightened budgets. CONCLUSIONS: The results indicate that
      despite the organizational support for CPD, respondents faced substantial
      challenges in accessing CPD when under pressure to achieve productivity targets,
      with little assistance in terms of funding. This discrepancy may indicate that
      greater support is required to meet MSK nurses' and AHPs' CPD needs.

PMID- 22961707
TI  - A case of gastrointestinal bleeding due to duodenal metastasis from a testicular
      choriocarcinoma.

PMID- 22961708
TI  - Uterine cervix metastasis from primary colorectal carcinoma: a report of two
      cases with review of literature.

PMID- 22961709
TI  - 1H and 13C NMR spectral assignments of novel chromenylchalcones.
AB  - Several types of chalcones containing 2H-chromen group were synthesized. Claisen
      Schmidt condensation of 2H-chromen-3-carbaldehydes (I) with methoxy substituted
      acetophenones afforded (E)-3-(2H-chromen-3-yl)-1-(methoxyphenyl)prop-2-en-1-ones
      (chromenylchalcones, 1-7). Other types of chromenylchalcone, (E)-1-(6-methoxy-2H
      chromen-3-yl)-3-(methoxyphenyl)prop-2-en-1-ones (8-13) were also obtained between
      reaction of methoxy substituted benzaldehydes and 1-(6-methoxy-2H-chromen-3
      yl)ethanone (II). Dichromenylchalcones (14-16) were also synthesized through the
      same reaction between aldehydes (I) and ketone (II). Their complete (1)H-NMR and
      (13)C-NMR assignments are reported here and more polysubstituted
      chromenylchalcones synthesized or isolated from the natural sources in the future
      can be identified on the basis of the NMR data reported here.

PMID- 22961710
TI  - Clinical, histologic, and genetic features of mesothelioma in a 7-year-old child.
AB  - Malignant mesothelioma (MM) is a highly aggressive malignancy that is extremely
      rare in children. This case report documents a 7-year-old male without previous
      asbestos exposure with peritoneal MM that initially responded to chemotherapy
      with cisplatin and gemcitabine but ultimately metastasized to his chest. He was
      diagnosed with MM based on histology, extensive immunohistochemical analyses, and
      an elevated serum CA-125 level. Cytogenetics and comparative genomic
      hybridization (CGH) analysis of his tumor identified a single extra copy number
      of chromosome 11 with few other changes noted.

PMID- 22961711
TI  - Chemical synthesis of a heparan sulfate glycopeptide: syndecan-1.

PMID- 22961712
TI  - The identification of inner tube defects in double-wall carbon nanotubes.
AB  - The precise atomic structure and relative atomic conformation of the individual
      carbon nanotubes comprising a double wall carbon nanotube (DWCNT) is determined.
      The DWCNTs are imaged using an aberration corrected high resolution transmission
      electron microscope (HRTEM) operating at 80 kV. Using processing in Fourier space
      images of the inner and outer tube of a double-wall carbon nanotube (DWCNT) are
      analysed. Comparisons of these results with simulated HRTEM images enable the
      chiral indices and relative atomic correlation of the component tubes of non
      commensurate DWCNTs to be determined. This technique is used to reveal the
      presence of a defect in the inner tube of a (6, 6)@(18, 2) DWCNT.

PMID- 22961713
TI  - Single determination of C-reactive protein at the time of diagnosis predicts long
      term outcome of patients with hepatocellular carcinoma.
AB  - We investigated the prognostic value of C-reactive protein (CRP) in patients with
      hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients
      diagnosed with HCC not amenable to surgery between April 1999 and December 2009
      at the Department of Gastroenterology of the Medical Universities of Vienna and
      Innsbruck were included. We assessed the optimal CRP cutoff by regression spline
      analysis and tested its impact on median overall survival (OS) by the Kaplan
      Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox
      proportional hazard regression model) in a training cohort (n = 466, Vienna) and
      an independent validation cohort (n = 149, Innsbruck). We found a sigmoid-shaped
      association of CRP and the hazard ratio of death upon regression spline analysis
      and defined a CRP level <1/>=1 mg/dL as optimal cutoff for further survival
      assessments. Elevated CRP (>=1 mg/dL) at diagnosis was associated with poor OS
      (CRP-elevated versus CRP-normal; 4 versus 20 months; P < 0.001) and remained a
      significant negative predictor for OS upon multivariate analysis (hazard ratio,
      1.7; P < 0.001), which was independent of age, Child-Pugh class, tumor
      characteristics, and treatment allocation. Analyses with respect to Barcelona
      Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of
      CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6
      versus 14; P < 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus
      CRP-normal, 4 versus 15 months; P < 0.001). The prognostic significance of
      elevated CRP was reproducible at a second CRP determination timepoint and
      confirmed in the independent validation cohort. CONCLUSION: Elevated CRP is
      associated with a dismal prognosis in HCC patients and may become a useful marker
      for patient selection in HCC management. (HEPATOLOGY 2012).

PMID- 22961714
TI  - Serial measurement of hepatic lipids during chemotherapy in patients with
      colorectal cancer: a 1 H MRS study.
AB  - Hepatic steatosis is a hallmark of chemotherapy-induced liver injury. We made
      serial (1) H MRS measurements of hepatic lipids in patients over the time course
      of a 24-week chemotherapeutic regimen to determine whether (1) H MRS could be
      used to monitor the progression of chemotherapy-induced steatosis. Thirty-four
      patients with stage III or IV colorectal cancer receiving 5-fluorouracil, folinic
      acid and oxaliplatin (n=21) or hepatic arterial infusion of floxuridine with
      systemic irinotecan (n=13) were studied prospectively. (1) H MRS studies were
      performed at baseline and after 6 and 24 weeks of treatment. A (1) H MR spectrum
      was acquired from the liver during a breath hold and the ratio of fat to
      fat+water (FFW) was calculated to give a measure of hepatic triglycerides
      (HTGCs). The methodology was histologically validated in 18 patients and the
      reproducibility was assessed in 16 normal volunteers. Twenty-seven patients
      completed baseline, 6-week and 24-week (1) H MRS examinations and one was
      censored. Thirteen of 26 patients (50%) showed an increase in FFW after
      completion of treatment. Six patients (23%) developed hepatic steatosis and two
      patients converted from steatosis to nonsteatotic liver. Patients whose 6-week
      hepatic lipid levels had increased significantly relative to baseline also had a
      high probability of lipid elevation relative to baseline at the completion of
      treatment. Serial (1) H MRS is effective for the monitoring of HTGC changes
      during chemotherapy and for the detection of chemotherapy-associated steatosis.
      Six of 26 patients developed steatosis during chemotherapy. Lipid changes were
      observable at 6 weeks.

PMID- 22961715
TI  - Post-translational modifications in activation and inhibition of Oct-1-DNA
      binding complex in H2B and other diverse gene regulation: prediction of interplay
      sites.
AB  - Octamer DNA binding transcription factors play important roles in housekeeping
      and specific gene regulations. Octamer DNA binding transcription factor-1 (Oct
      1), expressed ubiquitously, is a multifunctional molecule. The binding sites of
      Oct-1 are the promoters of H2B gene and the genes of snRNA, U2, U6, and 7SK, yet
      Oct-1 has been described as constitutively expressed transcription factor
      regulating the expression of housekeeping genes. Diverse tissue-specific genes
      regulations by Oct-1 include genes for interleukins (IL) 2, 3, 5; the granulocyte
      macrophagal colony-stimulating factor, immunoglobulins alpha, beta, Ly9; the
      endocrine-associated Pit-1 gene; the genes for gonadoliberin, prolactin, the
      thyroid transcription factor, and thyrotropin. The most interesting aspect of the
      gene regulations of Oct-1 includes both activation and inhibition of
      transcription. These opposite regulations of Oct-1 have been described through
      presence/absence of a post-translational modification (PTM) in its different
      domains. We propose a mechanism of interplay of different PTMs or
      presence/absence of PTMs in the different domains of Oct-1. We also suggest that
      the absence of phosphorylation and acetylation in G1 and S phases of the cell
      cycle is associated with interplay of methylation and O-GlcNAc modification. This
      interplay of O-GlcNAc modification with the phosphorylation and methylation with
      acetylation in POU sub-domain of Oct-1 may facilitate the formation of Oct-1-DNA
      complex, consequently activating H2B gene transcription. Whereas, in G2 and M
      phases these sites are occupied by phosphate resulting in inhibition of Oct-1-DNA
      complex formation leading to the suppression of H2B gene transcription.

PMID- 22961716
TI  - One-pot radical polymerization of one inimer to form one-dimensional polymeric
      nanomaterials.
AB  - A one-pot polymerization strategy is put forward for producing 1D polymeric
      nanomaterials directly from a single inimer. An inimer bearing an NMP initiating
      site is polymerized in the presence of a RAFT CTA to form a pearl-necklace
      structure constituted of hyperbranched polymer "pearls". The obtained 1D nanorods
      show high regularity evidenced by the long-range order in small angle XRD
      patterns and the formation of liquid crystalline phases.

PMID- 22961717
TI  - A validated microfluidics-based LC-chip-MS/MS method for the quantitation of
      fluoxetine and norfluoxetine in rat serum.
AB  - An increasing number of quantitative bioanalyses need to be performed on samples
      available in limited volumes, such as pharmacokinetic studies on small animals.
      In this context, microfluidic systems as the LC-chip device coupled to a mass
      spectrometer combine small sample volume requirements and high sensitivity. In
      this study, we present the development of a microfluidics-based method for
      fluoxetine (FLX) and norfluoxetine (NFL) quantitation dedicated to
      pharmacokinetic investigations in the rat serum. Using the methodology of
      experimental design, LC parameters were optimised in terms of peak resolution,
      analysis time, and sensitivity. An SPE method was then developed for serum
      samples on miniaturised 96-well plates containing a mixed-mode strong cation
      exchanger that provided very clean extracts with good analyte recovery (>=66.0%).
      The total SPE-LC-MS/MS process required only 20 MUL per sample and the method
      provided a good sensitivity in a total run time of 12 min. Finally, the developed
      method for FLX and NFL quantitation in rat serum was fully validated. After
      having selected the most appropriate regression model on the basis of the
      accuracy profiles, method selectivity, trueness, precision, accuracy and
      linearity were demonstrated.

PMID- 22961718
TI  - Inhibited prime-trial distractor responses solely produce the visual spatial
      negative priming effect.
AB  - Responding to a target's current (probe trial) location is slower when it appears
      at a former distractor-occupied position (i.e., ignored-repetition [IR] trial),
      relative to when it arises at a new location (i.e., control trial). This RT(IR) >
      RT(Control) inequality defines the spatial negative priming (SNP) effect in
      latency terms. It is uncertain whether the elevated RT(IR) is due to the
      inhibition of the distractor-occupied location or to the inhibition of this
      location's assigned manual response (SNP locus issue). The main aim here was to
      examine the SNP locus issue. Notably, our SNP design used centrally presented
      visual events and included having two locations share a common response (many:1
      location-to-response mapping) and the use of informative (70 % validity) or
      uninformative probe-trial response cues. The many:1 mapping trials allowed for
      the detection of location and response inhibition presence. Results showed that
      the latter, but not the former, causes inhibitory aftereffects (e.g., SNP)
      following uninformative response cues. Consistent with this finding, when the
      informative response cue was valid and was assigned to the many:1 probe response
      that had just served as the prime distractor response, inhibitory aftereffects
      were eliminated, when the probe target appeared at the prime distractor position
      (IR trial) or at a new location (distractor-response repeat trial). Blocked
      retrieval of stored distractor-processing representations was proposed as the
      mechanism for inhibitory aftereffect prevention.

PMID- 22961719
TI  - Attunement to haptic information helps skilled performers select implements for
      striking a ball in cricket.
AB  - This study examined the perceptual attunement of relatively skilled individuals
      to the physical properties of striking implements in the sport of cricket. We
      also sought to assess whether utilizing bats with different physical properties
      would influence performance of a specific striking action: the front foot
      straight drive. Eleven skilled male cricketers (mean age = 16.6 +/- 0.3 years)
      from an elite school cricket development program consented to participate in the
      study. While blindfolded, participants wielded six bats exhibiting different mass
      and moment of inertia (MOI) characteristics and were asked to identify the three
      bats they preferred the most for hitting a ball to a maximum distance by
      performing a front foot straight drive (a common shot in cricket). Next,
      participants actually attempted to hit balls projected from a ball machine using
      each of the six bat configurations to enable kinematic analysis of front foot
      straight drive performance with each implement. Results revealed that, on first
      choice, the two bats with the smallest mass and MOI values (1 and 2) were most
      preferred by almost two thirds (63.7 %) of the participants. Kinematic analysis
      of movement patterns revealed that bat velocity, step length, and bat-ball
      contact position measures significantly differed between bats. Data revealed how
      skilled youth cricketers were attuned to the different bat characteristics and
      harnessed movement system degeneracy to perform this complex interceptive action.

PMID- 22961721
TI  - Flow cytometry CD45-negative B-NHL: a case report of a diffuse large B-cell
      lymphoma without extranodal involvement.
AB  - BACKGROUND: The loss of CD45, the leukocyte-common antigen, has been described in
      rare cases of large B-cell lymphoma (LBCL) subtypes with extranodal involvement
      by immunohistochemical methods. Here we report a case of a patient with LBCL,
      with no extranodal lesions, which is CD45 negative by flow cytometry (FC)
      immunophenotyping. METHODS: Immunophenotyping and DNA content analysis was
      performed by multiparametric FC on lymph node and bone marrow aspirate obtained
      from a 65 year old male patient. RESULTS: Malignant B-lymphocytes were CD5-,
      CD10+/++, CD11c-, CD19+, CD20+/++, CD23-, CD34-, CD38-/+, CD45-, CD79b++/+++,
      BCL2 overexpressed, FMC7++, IgM++/+++, TdT- with Lambda light chain restriction.
      This pathological cellular population showed near-diploid DNA content, with a
      high proliferate rate. CONCLUSIONS: To our knowledge, we describe the first case
      of a CD19+ B-cell non-Hodgkin lymphoma without expression of CD45 detected by FC,
      and the first case without extranodal involvement presentation. This case is
      reported not only because it is a rare one but also to raise awareness of FC
      users of its correct diagnosis.

PMID- 22961720
TI  - Circulating branched-chain amino acid concentrations are associated with obesity
      and future insulin resistance in children and adolescents.
AB  - What is already known about this subject Circulating concentrations of branched
      chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle,
      and therefore may alter insulin sensitivity. BCAAs are elevated in adults with
      diet-induced obesity, and are associated with their future risk of type 2
      diabetes even after accounting for baseline clinical risk factors. What this
      study adds Increased concentrations of BCAAs are already present in young obese
      children and their metabolomic profiles are consistent with increased BCAA
      catabolism. Elevations in BCAAs in children are positively associated with
      insulin resistance measured 18 months later, independent of their initial body
      mass index. BACKGROUND: Branched-chain amino acid (BCAA) concentrations are
      elevated in response to overnutrition, and can affect both insulin sensitivity
      and secretion. Alterations in their metabolism may therefore play a role in the
      early pathogenesis of type 2 diabetes in overweight children. OBJECTIVE: To
      determine whether paediatric obesity is associated with elevations in fasting
      circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether
      these elevations predict future insulin resistance. METHODS: Sixty-nine healthy
      subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of
      subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a
      prospective longitudinal cohort for 18 months (n = 17 with complete data).
      RESULTS: Elevations in the concentrations of BCAAs were significantly associated
      with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross
      sectional cohort. In the subset of subjects that followed longitudinally,
      baseline BCAA concentrations were positively associated with homeostasis model
      assessment for insulin resistance measured 18 months later after controlling for
      baseline clinical factors including BMI Z-score, sex and pubertal stage (P =
      0.046). CONCLUSIONS: Elevations in the concentrations of circulating BCAAs are
      significantly associated with obesity in children and adolescents, and may
      independently predict future insulin resistance.

PMID- 22961722
TI  - Cold-active hydrolases producing bacteria from two different sub-glacial
      Himalayan lakes.
AB  - Microorganisms, native to the cold environments have successfully acclimatized
      their physiological, metabolic, and biological features, exhibiting uniqueness in
      their enzymes, proteins, and membrane structures. These cold-active enzymes have
      immense biotechnological potential. The diversity of culturable bacteria in two
      different water lakes (the sub-glacial freshwater and the brackish) of Himalayas
      was analyzed using SYBR green staining and cultural methods. A total of 140
      bacteria were isolated and were grouped as psychrophiles, psychrotrophs, and
      psychrotolerant organisms, based on their optimal temperature for growth. The
      amplified ribosomal DNA restriction analysis using three restriction enzymes
      facilitated the grouping of these isolates into 96 genotypes at >=85%
      polymorphism. Phylogenetic analysis using 16S rRNA gene sequences revealed that
      the bacterial strains from both lakes belonged to Firmicutes, Proteobacteria
      (alpha, beta, and gamma) or Actinobacteria. Screening of the germplasm for the
      activity of different cold-active hydrolases such as protease, amylase, xylanase,
      and cellulase, revealed that about 16 isolates were positive, and exhibiting a
      wide range of stability at various temperature and pH. Our results suggest that
      the distinctly different ecosystems of sub-glacial freshwater and brackish water
      lakes have diverse groups of bacteria, which can be an excellent source of
      extracellular hydrolases with a wide range of thermal stability. 

PMID- 22961724
TI  - The Goldilocks conundrum for optimal macronutrient delivery in the PICU--too
      much, too little, or just right?

PMID- 22961723
TI  - ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem
      cell.
AB  - The differentiation of stem-like tumor cells may contribute to the cellular
      heterogeneity of breast cancers. We report the propagation of highly enriched
      mouse mammary cancer stem cells that retain the potential to differentiate both
      in vivo and in culture and their use to identify chemical compounds that
      influence both self-renewal and differentiation. We identify epithelial tumor
      initiating cells (ETICs) that express lineage markers of both basal and luminal
      mammary cell lineages and retain the potential, from even single cells, to
      generate heterogeneous tumors similar to the tumor of origin. ETICs can progress
      through a Rho-associated coiled-coil containing protein kinase 1 dependent,
      epithelial to mesenchymal transition to generate mesenchymal tumor-initiating
      cells capable of initiating tumors of limited heterogeneity. The propagation of
      ETICs may allow for the identification of new therapeutic compounds that may
      inhibit or prevent progression of some types of breast cancer.

PMID- 22961725
TI  - Evaluation of zebrafish brain development using optical coherence tomography.
AB  - The zebrafish is a well-established model system used to study and understand
      various human biological processes. The present study used OCT to investigate
      growth of the adult zebrafish brain. Twenty zebrafish were studied, using their
      standard lengths as indicators of their age. Zebrafish brain aging was evaluated
      by analyzing signal attenuation rates and texture features in regions of interest
      (ROIs). Optical scattering originates from light interaction with biological
      structures. During development, the zebrafish brain gains cells. Signal
      attenuation rate, therefore, increases with increasing zebrafish brain age. This
      study's analyses of texture features could not identify aging in zebrafish brain.
      These results, therefore, indicated that the OCT signal attenuation rate can
      indicate zebrafish brain aging, and its analysis provides a more effective means
      of observing zebrafish brain aging than texture features analysis. Using OCT
      system could further increase the technique's potential for recognition and
      monitoring of zebrafish brain development.

PMID- 22961726
TI  - High-precision calibration of MRS thermometry using validated temperature
      standards: effects of ionic strength and protein content on the calibration.
AB  - Currently, there is very limited ability to measure the temperature of the brain,
      but a direct technique for its estimation in vivo could improve the detection of
      patients at risk of temperature-related brain damage, help in the diagnosis of
      stroke and tumour, and provide useful information on the mechanisms of
      thermoregulation of the brain. In this article, new calibrations in vitro of MRS
      thermometry using temperature-stabilised reference phantoms are reported. The
      phantoms comprise two concentric glass spheres: the inner sphere contains the
      phantom material to be measured by MRS, and the outer sphere contains a substance
      with a known temperature stable to within 0.2  degrees C. The substances were
      freezing organic fixed-point compounds (diphenyl ether and ethylene carbonate,
      freezing at 26.3 and 35.8  degrees C, respectively) or temperature-controlled
      circulating water. The phantom temperature was continuously monitored with a
      fluoroptic probe calibrated at the National Physical Laboratory with traceability
      to the International Temperature Scale 1990 (ITS-90). The MRS temperature
      calibration was obtained by measuring the chemical shift of water relative to N
      acetylaspartate (NAA) in a single voxel as a function of temperature using a 1.5
      T Philips Intera scanner. Measurements were made for several phantom materials to
      assess the effect of tissue composition on the water-NAA chemical shift against
      temperature calibration. The phantom mixtures contained 25 mm of NAA buffered to
      pH 6.5 or 7.5 and several ionic salts or bovine serum albumin (BSA). Spectra were
      acquired from 25 to 45  degrees C. The correlation between frequency differences
      and phantom temperature was very linear with small residuals. However, the linear
      fitting parameters varied with ionic composition and BSA concentration. The
      'apparent' temperature (calibrated using the water-NAA frequency differences)
      decreased by approximately 1  degrees C for every 100 mm increase in ionic
      concentration and increased proportionally to the concentration of BSA.

PMID- 22961728
TI  - Temperature-activated reverse sensing behavior of Pd nanowire hydrogen sensors.
AB  - Hydrogen sensors built with individual palladium nanowires (Pd NWs) have been
      achieved by integrating Pd NWs across microelectromechanical system (MEMS)
      electrodes, followed by assembling and bonding them to a chip carrier platform.
      The sensing measurements reveal that the sensors with individual Pd NWs show
      reverse sensing behaviors between the temperature zones of (370-263 K) and (263
      120 K).

PMID- 22961727
TI  - Ammonia control and neurocognitive outcome among urea cycle disorder patients
      treated with glycerol phenylbutyrate.
AB  - Glycerol phenylbutyrate is under development for treatment of urea cycle
      disorders (UCDs), rare inherited metabolic disorders manifested by hyperammonemia
      and neurological impairment. We report the results of a pivotal Phase 3,
      randomized, double-blind, crossover trial comparing ammonia control, assessed as
      24-hour area under the curve (NH3 -AUC0-24hr ), and pharmacokinetics during
      treatment with glycerol phenylbutyrate versus sodium phenylbutyrate (NaPBA) in
      adult UCD patients and the combined results of four studies involving short- and
      long-term glycerol phenylbutyrate treatment of UCD patients ages 6 and above.
      Glycerol phenylbutyrate was noninferior to NaPBA with respect to ammonia control
      in the pivotal study, with mean (standard deviation, SD) NH3 -AUC0-24hr of 866
      (661) versus 977 (865) MUmol.h/L for glycerol phenylbutyrate and NaPBA,
      respectively. Among 65 adult and pediatric patients completing three similarly
      designed short-term comparisons of glycerol phenylbutyrate versus NaPBA, NH3 
      AUC0-24hr was directionally lower on glycerol phenylbutyrate in each study,
      similar among all subgroups, and significantly lower (P < 0.05) in the pooled
      analysis, as was plasma glutamine. The 24-hour ammonia profiles were consistent
      with the slow-release behavior of glycerol phenylbutyrate and better overnight
      ammonia control. During 12 months of open-label glycerol phenylbutyrate
      treatment, average ammonia was normal in adult and pediatric patients and
      executive function among pediatric patients, including behavioral regulation,
      goal setting, planning, and self-monitoring, was significantly improved.
      CONCLUSION: Glycerol phenylbutyrate exhibits favorable pharmacokinetics and
      ammonia control relative to NaPBA in UCD patients, and long-term glycerol
      phenylbutyrate treatment in pediatric UCD patients was associated with improved
      executive function (ClinicalTrials.gov NCT00551200, NCT00947544, NCT00992459,
      NCT00947297). (HEPATOLOGY 2012).

PMID- 22961729
TI  - Using ligand-mapping simulations to design a ligand selectively targeting a
      cryptic surface pocket of polo-like kinase 1.

PMID- 22961730
TI  - Rapid and sensitive LC-MS/MS method for determination of megestrol acetate in
      human plasma: application to a human pharmacokinetic study.
AB  - A rapid, simple and fully validated LC-MS/MS method was developed and validated
      for the determination of megestrol acetate in human plasma using tolbutamide as
      an internal standard (IS) after one-step liquid-liquid extraction with methyl
      tert-butyl-ether. Detection was performed using electrospray ionization in
      positive ion multiple reaction monitoring mode by monitoring the transitions m/z
      385.5 -> 267.1 for megestrol acetate and m/z 271.4 -> 155.1 for IS.
      Chromatographic separation was performed on a YMC Hydrosphere C18 column with an
      isocratic mobile phase, which consisted of 10 mm ammonium formate buffer
      (adjusted to pH 5.0 with formic acid)-methanol (60:40, v/v) at a flow rate of 0.4
      mL/min. The achieved lower limit of quantitation (LLOQ) was 1 ng/mL (signal-to
      noise ratio > 10) and the standard calibration curve for megestrol acetate was
      linear (r > 0.99) over the studied concentration range (1-2000 ng/mL). The
      proposed method was fully validated by determining its specificity, linearity,
      LLOQ, intra- and inter-day precision and accuracy, recovery, matrix effect and
      stability. The validated LC-MS/MS method was successfully applied for the
      evaluation of pharmacokinetic parameters of megestrol acetate after oral
      administration of a single dose 800 mg of megestrol acetate (MegaceTM) to five
      healthy Korean male volunteers under fed conditions.

PMID- 22961731
TI  - Genetic diversity of internalin genes in the ascB-dapE locus among Listeria
      monocytogenes lineages III and IV strains.
AB  - Listeria monocytogenes is an important foodborne pathogen encompassing four
      phylogenetic lineages. Lineages III and IV are rare, but have been reported to
      show considerable biodiversity, providing important clues for the evolutionary
      history in Listeria. In this study, analysis of the ascB-dapE locus reveals
      genetic diversity in lineages III and IV, and is consistent with the
      classification of sublineages. Four of the six genetic patterns (two of
      sublineage IIIC and two of lineage IV) are specific to these two lineages. The
      ascB-dapE locus suggests a hot spot for genome diversification, and serves as an
      attractive molecular marker for better understanding of the biodiversity and
      population structure of lineages III and IV strains. 

PMID- 22961732
TI  - Surveillance following head, neck, and chest radiotherapy: thyroid ultrasound
      monitoring for secondary thyroid malignancy.
AB  - Children who receive head, neck, or chest radiotherapy for various primary
      malignancies have increased risk for secondary thyroid malignancy. Thyroid
      nodules are difficult to identify by physical examination and/or laboratory
      tests. Thyroid ultrasound can detect non-palpable nodules without adverse side
      effects. We performed a retrospective chart review of 36 patients who received
      radiotherapy and underwent thyroid ultrasound. Forty-seven percent (n = 17) had
      >=1 nodule(s) detected. Seven patients underwent thyroidectomy; four of whom were
      diagnosed with thyroid malignancy. Our study suggests routine use of thyroid
      ultrasound in high-risk patients detects subclinical thyroid nodules and
      potential thyroid malignancy post-radiotherapy.

PMID- 22961733
TI  - Maxillary sinus augmentation using computer-aided design/computer-aided
      manufacturing (CAD/CAM) technology.
AB  - BACKGROUND: Maxillary sinus augmentation is a common method for increasing bone
      height for insertion of dental implants. In most cases, the graft is manually cut
      into a roughly appropriate shape by visual estimation during the operation;
      accordingly, the shape of the graft depends considerably on the experience of the
      surgeon. We have developed a computer-aided design/computer-aided manufacturing
      (CAD/CAM) technique to generate custom-made block grafts for sinus augmentation,
      and a customized cutting guide to precisely position the lateral wall and
      facilitate membrane elevation, using cone-beam computed tomography (CBCT).
      METHODS: Custom-made blocks of hydroxyapatite (HA) were preoperatively cut to the
      required shape, based on a three-dimensional (3D) simulation, using CAD/CAM
      technology. The custom-made HA blocks were used for sinus augmentation. RESULTS:
      Five patients underwent bilateral sinus elevation with custom-made HA blocks. Six
      months later, implants were placed. Two years after placement, all implants were
      in function. No clinical or prosthetic complications were encountered.
      CONCLUSIONS: We present a CAD/CAM technique for the fabrication of custom-made
      block grafts for sinus augmentation.

PMID- 22961735
TI  - The phenotypic distribution and functional profile of tuberculin-specific CD4 T
      cells characterizes different stages of TB infection.
AB  - BACKGROUND: Recent publications have suggested that altered proportions of
      functional CD4 T-cell subsets correlate with active pulmonary TB. Also, CD27
      expression on tuberculin-activated IFN-gamma(+) CD4 T-cells is known to differ
      significantly between patients with active pulmonary TB and healthy TB-unexposed
      BCG vaccinees. Here, we explore links between CD4 T-cell phenotype, multiple
      functional subsets, and control of TB. METHODS: We examined ex-vivo overnight
      tuberculin activated CD4 T-cells in regards to CD27-expression and the activation
      markers, CD154 upregulation, IFN-gamma, TNF-alpha, IL-2, and degranulation in 44
      individuals, including cases of clinically active pulmonary TB, and hospital
      staff with prolonged TB exposure, some of whom had latent TB. RESULTS: Active
      pulmonary TB generally showed an excess of TNF-alpha(+) subsets over IFN-gamma(+)
      subsets, paralleled by decreased CD27 expression on activated IFN-gamma(+) or
      CD154(+) CD4 T-cells. The single subset distinguishing best between active
      pulmonary TB and high TB exposure was CD154(+) /TNF-alpha(+) / IFN-gamma(-) /IL
      2(-) /degranulation(-) (AUROC 0.90). The ratio between the frequencies of TNF
      alpha(+) /IFN-gamma(+) CD4 T-cells was an effective alternative parameter (AUROC
      0.87). CONCLUSIONS: Functional subsets and phenotype of tuberculin induced CD4 T
      cells differ between stages of TB infection. Predominance of TNF-alpha(+) CD4 T
      cells in active infection suggests an increased effort of the immune system to
      contain disease.

PMID- 22961736
TI  - Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide
      generation in lambs with surgically induced acute increases in pulmonary blood
      flow.
AB  - We have previously shown that acute increases in pulmonary blood flow (PBF) are
      limited by a compensatory increase in pulmonary vascular resistance (PVR) via an
      endothelin-1 (ET-1) dependent decrease in nitric oxide synthase (NOS) activity.
      The mechanisms underlying the reduction in NO signaling are unresolved. Thus, the
      purpose of this study was to elucidate mechanisms of this ET-1-NO interaction.
      Pulmonary arterial endothelial cells were acutely exposed to shear stress in the
      presence or absence of tezosentan, a combined ET(A) /ET(B) receptor antagonist.
      Shear increased NO(x) , eNOS phospho-Ser1177, and H(2) O(2) and decreased
      catalase activity; tezosentan enhanced, while ET-1 attenuated all of these
      changes. In addition, ET-1 increased eNOS phospho-Thr495 levels. In lambs, 4 h of
      increased PBF decreased H(2) O(2) , eNOS phospho-Ser1177, and NO(X) levels, and
      increased eNOS phospho-Thr495, phospho-catalase, and catalase activity. These
      changes were reversed by tezosentan. PEG-catalase reversed the positive effects
      of tezosentan on NO signaling. In all groups, opening the shunt resulted in a
      rapid increase in PBF by 30 min. In vehicle- and tezosentan/PEG-catalase lambs,
      PBF did not change further over the 4 h study period. PVR fell by 30 min in
      vehicle- and tezosentan-treated lambs, and by 60 min in tezosentan/PEG-catalase
      treated lambs. In vehicle- and tezosentan/PEG-catalase lambs, PVR did not change
      further over the 4 h study period. In tezosentan-treated lambs, PBF continued to
      increase and LPVR to decrease over the 4 h study period. We conclude that acute
      increases in PBF are limited by an ET-1 dependent decrease in NO production via
      alterations in catalase activity, H(2) O(2) levels, and eNOS phosphorylation.

PMID- 22961738
TI  - A surfactant-based, regularly arrayed nanostructure gel matrix for migration of
      small molecules.
AB  - The preparation of nanometer-scale pores, or nanopores, has become easy because
      of the progress in nanotechnology. Surfactants are promising materials for the
      preparation of nanostructures containing nanopores, because surfactants form many
      different phase structures, including cubic, micellar, and lamellar structures.
      We prepared a gel matrix with a cubic structure from a commercially available
      surfactant, polyoxyethylene(50) lauryl ether (C12EO50, Adekatol LA-50). This gel
      matrix had regularly arrayed nanopores between the packed spherical micelles. We
      used the gel to separate biomolecules by means of slab gel electrophoresis. The
      gel was applicable to migration of amino acids and peptides; however, larger
      molecules, such as proteins and single-walled carbon nanotubes, did not migrate
      through the gel. We concluded that the pore size was too small for the
      penetration of large molecules, and that only small molecules could penetrate the
      gel matrix. The migration mechanism of small molecules was similar to that
      observed in conventional gel electrophoresis. We concluded that the gel matrix
      prepared from surfactant is a promising matrix for migration and purification of
      small molecules. We also expect that the gel can be used as a nanoscale filter to
      trap large molecules, allowing only small molecules to pass.

PMID- 22961737
TI  - Expanding the concepts and tools of metabolic engineering to elucidate cancer
      metabolism.
AB  - The metabolic engineer's toolbox, comprising stable isotope tracers, flux
      estimation and analysis, pathway identification, and pathway kinetics and
      regulation, among other techniques, has long been used to elucidate and quantify
      pathways primarily in the context of engineering microbes for producing small
      molecules of interest. Recently, these tools are increasingly finding use in
      cancer biology due to their unparalleled capacity for quantifying intracellular
      metabolism of mammalian cells. Here, we review basic concepts that are used to
      derive useful insights about the metabolism of tumor cells, along with a number
      of illustrative examples highlighting the fundamental contributions of these
      methods to elucidating cancer cell metabolism. This area presents unique
      opportunities for metabolic engineering to expand its portfolio of applications
      into the realm of cancer biology and help develop new cancer therapies based on a
      new class of metabolically derived targets.

PMID- 22961739
TI  - Tissue lipids and drug distribution: dog versus rat.
AB  - A key parameter in whole-body physiologically based pharmacokinetic models is the
      tissue-to-plasma water partition coefficient (K(pu)), which is commonly assumed
      consistent across all species for all tissues for passively distributing drugs.
      Many drugs primarily bind to tissue lipids and although considerable tissue lipid
      concentration data exist in rodents, data on these and K(pu) values in larger
      animals and humans are sparse to negligible. To test the above assumption, lipid
      levels were quantified in 13 dog tissues, then compared with the values in rat,
      and used to predict and compare K(pu) values between these species. For many
      tissues, including muscle, lipid concentrations were comparable in dog and rat.
      However, spleen acidic phospholipid levels were sevenfold lower, skin neutral
      phospholipid threefold lower, and neutral lipids fivefold, 12-fold, and eightfold
      lower in brain, lung, and spleen, respectively, and fourfold higher in bone in
      dog than in rat. Such differences resulted in significant predicted K(pu)
      differences. In contrast, unbound volume of distribution (Vu(ss)), a global
      measure of distribution, showed generally good agreement (predictions and
      observations) between dog and rat for a diverse compound set, indicating tissues
      with large-predicted K(pu) species differences tend either to contribute to
      Vu(ss) to a limited extent, and/or occur in opposing directions tending to cancel
      each other out.

PMID- 22961740
TI  - Visual search enhances subsequent mnemonic search.
AB  - We examined how the performance of a visual search task while studying a list of
      to-be-remembered words affects subsequent memory for those words by humans.
      Previous research had suggested that episodic context encoding is facilitated
      when the study phase of a memory experiment requires, or otherwise encourages, a
      visual search for the to-be-remembered stimuli, and theta-band oscillations are
      more robust when animals are searching their environment. Moreover, hippocampal
      theta oscillations are positively correlated with learning in animals. We assumed
      that a visual search task performed during the encoding of words for a subsequent
      memory test would induce an exploratory state that would mimic the one that is
      induced in animals when performing exploratory activities in their environment,
      and that the encoding of episodic traces would be improved as a result. The
      results of several experiments indicated that the performance of the search task
      improved free recall, but the results did not extend to yes-no or forced choice
      recognition memory testing. We propose that visual search tasks enhance the
      encoding of episodic context information but do not enhance the encoding of to-be
      remembered words.

PMID- 22961741
TI  - Histone deacetylase inhibition mediates urocortin-induced antiproliferation and
      neuronal differentiation in neural stem cells.
AB  - During cortical development, cell proliferation and cell cycle exit are carefully
      regulated to ensure that the appropriate numbers of cells are produced. Urocortin
      (UCN) is a member of the corticotrophin releasing hormone (CRH) family of
      neuropeptides that regulates stress responses. UCN is widely distributed in adult
      rat brain. However, the expression and function of UCN in embryonic brain is, as
      yet, unclear. Here, we show that UCN is endogenously expressed in proliferative
      zones of the developing cerebral cortex and its receptors are exhibited in neural
      stem cells (NSCs), thus implicating the neuropeptide in cell cycle regulation.
      Treatment of cultured NSCs or organotypic slice cultures with UCN markedly
      reduced cell proliferation. Furthermore, blocking of endogenous UCN/CRHRs system
      either by treatment with CRHRs antagonists or by neutralization of secreted UCN
      with anti-UCN antibody increased NSCs proliferation. Cell cycle kinetics analysis
      demonstrated that UCN lengthened the total cell cycle duration via increasing the
      G1 phase and accelerated cell cycle exit. UCN directly inhibited the histone
      deacetylase (HDAC) activity and induced a robust increase in histone H3
      acetylation levels. Using pharmacological and RNA interference approaches, we
      further demonstrated that antiproliferative action of UCN appeared to be mediated
      through a HDAC inhibition-induced p21 upregulation. Moreover, UCN treatment in
      vitro and in vivo led to an increase in neuronal differentiation of NSCs. These
      findings suggest that UCN might contribute to regulate NSCs proliferation and
      differentiation during cortical neurogenesis.

PMID- 22961742
TI  - Polymersomes containing a hydrogel network for high stability and controlled
      release.
AB  - Capillary microfluidic devices are used to prepare monodisperse polymersomes
      consisting of a hydrogel core and a bilayer membrane of amphiphilic diblock
      copolymers. To make polymersomes, water-in-oil-in-water double-emulsion drops are
      prepared as templates through single-step emulsification in a capillary
      microfluidic device. The amphiphile-laden middle oil phase of the double-emulsion
      drop dewets from the surface of the innermost water drop, which contains hydrogel
      prepolymers; this dewetting leads to the formation of a bilayer membrane.
      Subsequently, the oil phase completely separates from the innermost water drop,
      leaving a polymersome. Upon UV illumination of the polymersome, the prepolymers
      encapsulated within the interior are crosslinked, forming a hydrogel core. The
      hydrogel network within the polymersomes facilitates sustained release of the
      encapsulated materials and increases the stability of the polymersomes through
      the formation of a scaffold to support the bilayer. In addition, this approach
      provides a facile method to make monodisperse hydrogel particles directly
      dispersed in water.

PMID- 22961743
TI  - Introducing the AASLD president: Guadalupe Garcia-Tsao.

PMID- 22961744
TI  - Potentially biomimetic total synthesis and relative stereochemical assignment of
      (+/-)-gracilamine.

PMID- 22961745
TI  - Angular benzoperylenetetracarboxylic bisimides.
AB  - Benzoperylene derivatives with two angularly attached dicarboxylic imide rings,
      which were prepared by the Diels-Alder-reaction, exhibit strong fluorescence and
      their free peri positions allow either control of the UV/Vis spectra through
      their substituents or form anchor positions for the attachment of functional
      units. The angular chromophore 3 may be used both for fluorescent labeling such
      as for primary amines or enzymes or as building blocks for more complex
      assemblies where they may act as energy donors for FRET or electron acceptors in
      PET such as for photovoltaic solar cells.

PMID- 22961746
TI  - Rapid Identification of unstable acyl glucoside flavonoids of Oxytropis racemosa
      Turcz by high-performance liquid chromatography-diode array detection
      electrospray ionisation/multi-stage mass spectrometry.
AB  - INTRODUCTION: Oxytropis racemosa Turcz is an important minority medicine that is
      used mainly to improve children's indigestion, especially in inner Mongolia and
      Tibet. Previous studies indicated that the characteristic constituents of this
      plant are acylated flavonoids. OBJECTIVE: Rapidly identify the characteristic
      chemical constituents of O. racemosa by high-performance liquid chromatography
      diode array detection-electrospray ionisation/multi-stage mass spectrometry (HPLC
      DAD-ESI/MS(n) ) and suggest a useful method to control the quality of this
      medicinal plant. METHODS: In the HPLC fingerprint, 32 flavonoids were tentatively
      identified by a detailed analysis of their mass spectra, UV spectra and retention
      times. Furthermore, 13 flavonoids were confirmed by comparison with previously
      isolated compounds obtained from O. racemosa. RESULTS: In total, 32 flavonoids,
      including 13 flavonoids with 3-hydroxy-3-methylglutaric acid (HMG) moieties and
      four flavonoids with 3-malonyl moieties, were identified in the extract of O.
      racemosa. Among the compounds identified, 10 were characterised as new compounds
      for their particular acylated sugar moieties. CONCLUSIONS: The method described
      is effective for obtaining a comprehensive phytochemical profile of plants
      containing unstable acylated flavonoids. The method is also useful for
      constructing the chromatographic fingerprint of the minority medicine -O.
      racemosa Turcz for quality control.

PMID- 22961747
TI  - Electrocatalytic reduction of acetone in a proton-exchange-membrane reactor: a
      model reaction for the electrocatalytic reduction of biomass.
AB  - Acetone was electrocatalytically reduced to isopropanol in a proton-exchange
      membrane (PEM) reactor on an unsupported platinum cathode. Protons needed for the
      reduction were produced on the unsupported Pt-Ru anode from either hydrogen gas
      or electrolysis of water. The current efficiency (the ratio of current
      contributing to the desired chemical reaction to the overall current) and
      reaction rate for acetone conversion increased with increasing temperature or
      applied voltage for the electrocatalytic acetone/water system. The reaction rate
      and current efficiency went through a maximum with respect to acetone
      concentration. The reaction rate for acetone conversion increased with increasing
      temperature for the electrocatalytic acetone/hydrogen system. Increasing the
      applied voltage for the electrocatalytic acetone/hydrogen system decreased the
      current efficiency due to production of hydrogen gas. Results from this study
      demonstrate the commercial feasibility of using PEM reactors to
      electrocatalytically reduce biomass-derived oxygenates into renewable fuels and
      chemicals.

PMID- 22961748
TI  - Serum proteomic profiling for the early diagnosis of colorectal cancer.
AB  - No ideal serum biomarker currently exists for the early diagnosis of colorectal
      cancer (CRC). Magnetic bead-based fractionation coupled with MALDI-TOF MS was
      used to screen serum samples from CRC patients, healthy controls, and other
      cancer patients. A diagnostic model with five proteomic features (m/z 1778.97,
      1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with
      best performance. The Fisher-based model could discriminate CRC patients from the
      controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the
      training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test
      set. We further validated the model with 94.4% (254/269) sensitivity and 75.5%
      (83/110) specificity in the external independent group. In other cancers group,
      the Fisher-based model classified 25 of 46 samples (54.3%) as positive and the
      other 21 as negative. With FT-ICR-MS, the proteomic features of m/z 1778.97,
      1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in
      CRC, were identified as fragments of complement C3f. Therefore, the Fisher-based
      model containing five proteomic features was able to effectively differentiate
      CRC patients from healthy controls and other cancers with a high sensitivity and
      specificity, and may be CRC-specific. Serum complement C3f, which was
      significantly decreased in CRC group, may be relevant to the incidence of CRC.

PMID- 22961749
TI  - Nigerian resident doctors on strike: insights from and policy implications of job
      satisfaction among resident doctors in a Nigerian teaching hospital.
AB  - OBJECTIVES: The Nigerian health system has been engulfed in a crisis occasioned
      by a deluge of strike actions by resident doctors in recent times.
      Dissatisfaction with conditions of service has been cited as the bone of
      contention. Job satisfaction studies among doctors have provided insights into
      the contributory factors to recurrent industrial disputes in other climes. This
      study aims to determine the predictors of job satisfaction among resident doctors
      in a tertiary healthcare centre in Nigeria. This is with a view to gain some
      insights into the possible contributory factors to industrial disputes and to
      discuss the policy implications of such findings. METHODS: A semi-structured
      questionnaire was used to obtain socio-demographic characteristics and job
      related determinants of job satisfaction among resident doctors. Logistic
      regression analysis was carried out to determine predictors of job satisfaction.
      FINDINGS: A total of 163 resident doctors completed the study. Overall, 90
      (55.2%) of the resident doctors were satisfied with their jobs. Lower age, career
      advancement opportunities, autonomy of practice, alignment of job with core
      personal and professional values, and working environment predicted job
      satisfaction. CONCLUSIONS: To restore satisfaction and possibly stem industrial
      disputes by resident doctors, government of Nigeria needs to sustain current
      wages while introducing non-financial benefits. There is a need to adopt policies
      geared towards increasing government spending on health especially in the area of
      human capacity and infrastructural development, so as to afford resident doctors
      opportunities for skill acquisition and career development.

PMID- 22961750
TI  - Outcome of patients with localized orbital sarcoma who relapsed following
      treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and 
      IV, 1984-1997: a report from the Children's Oncology Group.
AB  - BACKGROUND: We wanted to ascertain patterns of recurrence, re-treatment, and
      outcome among 188 eligible patients treated for localized orbital sarcoma on IRSG
      Protocols III/IV, 1984-1997. PROCEDURE: Retrospective chart review. RESULTS:
      Twenty-four of 188 patients (12.8%) developed local (n = 22) or distant relapse
      (n = 2) at 0.057-7.05 years (median, 1.58) after enrollment. Ages at study entry
      were 0.14-17 years (median, 5 years). Initial tumor operations included biopsy (n
      = 20) or gross resection with microscopic residual (n = 4). Initial tumor
      diameters were 0.5-7 cm (median, 3). Pathologic subtypes were embryonal
      rhabdomyosarcoma (ERMS, n = 19), sarcoma not otherwise specified (n = 2), and
      alveolar RMS, botryoid ERMS, or undifferentiated sarcoma (n = 1 each). Initial
      treatment included vincristine/dactinomycin (n = 24) including an alkylator (n =
      4) and radiotherapy (RT, n = 21). Twenty patients responded, 14 completely, 6
      partially. After recurrence, patients underwent orbital exenteration (n = 10),
      enucleation (2), tumor excision (3), or biopsy (1); 7 had no operation, and 1 had
      no data. Post-relapse chemotherapy included combinations of etoposide (n = 14
      patients), doxorubicin (14), ifosfamide (12), cyclophosphamide (7), and
      dacarbazine (n = 1). Six patients received RT, including four previously treated
      and two not irradiated initially. Two patients died; one at 1.79 years after
      contralateral brain metastasis followed by local recurrence, and another at 2.49
      years after multiple local recurrences. Twenty-two patients (91.7%) survived
      sarcoma-free for 0.04-17 years (median, 6.9) after relapse, and 18 of 22 (82%)
      were alive >=5 years after relapse. CONCLUSION: Survival following recurrent
      localized orbital sarcoma appears likely after vigorous re-treatment given with
      curative intent.

PMID- 22961751
TI  - Disclosure of a fundamental clue for the elucidation of the myricetin mechanism
      of action as amyloid aggregation inhibitor by mass spectrometry.
AB  - Progression of Alzheimer's disease involves aggregation of amyloid-beta (Abeta)
      peptides, a complex process that involves the formation of several soluble
      intermediates and ends up with the deposition of ordered fibrillar architectures.
      The determination of the Abeta42 self-assembly species targeted by an inhibitor
      is a key step in the identification of new inhibitors endowed with a suitable
      profile. In this context, the subtle characterization of myricetin (Myr) mode of
      action at a molecular level was performed by using different MS techniques, which
      allowed the monitoring of the modifications induced by Myr on the first occurring
      Abeta42 self-assembly species. Results showed a persistent level of monomer and
      decreased formation of ordered Abeta42 aggregates in the presence of Myr,
      further, nano-LC-nano-ESI-QTOF, MALDI-TOF, and ESI-IT highlighted the formation
      of a new oxidized Abeta42 species, which is less prone to aggregation, in the
      presence of Myr. Coupling tryptic digestion and nano-LC-nano-ESI-QTOF also
      allowed the identification of Met(35)  as the specific site of oxidation along
      the Abeta aminoacid chain. Therefore, the detailed investigation by different MS
      techniques allowed better understanding of the molecular modification at the
      basis of the antiaggregating properties of Myr and highlighted its oxidizing
      action on the residue Met(35)  in Abeta monomers.

PMID- 22961752
TI  - A 2,3-butanediol dehydrogenase from Paenibacillus polymyxa ZJ-9 for mainly
      producing R,R-2,3-butanediol: purification, characterization and cloning.
AB  - A 2,3-butanediol dehydrogenase (BDH) from Paenibacillus polymyxa ZJ-9 was
      purified to homogeneity via fractional ammonium sulfate precipitation, followed
      by two steps of anion-exchange chromatography using DEAE-Sepharose and Source
      15Q, obtaining a 35-fold increase in specific activity and 34.9% yield. The
      molecular weights of the purified BDH subunit and holoenzyme were 44.5 and 90.0
      kDa, respectively, as detected via SDS-PAGE and gel filtration chromatography.
      These results were significantly different from those of other reported BDHs.
      Substrate specificity experiments showed that the enzyme could function
      preferentially as a reductase rather than as a dehydrogenase, and was mainly
      responsible for the reduction of R-acetoin to R,R-2,3-butanediol. Gene cloning,
      sequencing, and expression experiments further demonstrate that this enzyme was a
      new type of BDH. 

PMID- 22961753
TI  - Fermentation behavior of an osmotolerant yeast D. hansenii for Xylitol
      production.
AB  - Realizing the importance of xylitol as a high-valued compound that serves as a
      sugar substitute, a new, one step thin layer chromatographic procedure for quick,
      reliable, and efficient determination of xylose and xylitol from their mixture
      was developed. Two hundred and twenty microorganisms from the laboratory stock
      cultures were screened for their ability to produce xylitol from D-xylose.
      Amongst these, an indigenous yeast isolate no.139 (SM-139) was selected and
      identified as Debaryomyces hansenii on the basis of morphological and biochemical
      characteristics and (26S) D1/D2 r DNA region sequencing. Debaryomyces hansenii
      produced 9.33 gL(-1) of xylitol in presence of 50.0 gL(-1) of xylose in 84 h at
      pH 5.5, 30 degrees C, 200 rpm. In order to utilize even higher concentrations of
      xylose for maximum xylitol production, a xylose enrichment technique was
      developed. The strain of Debaryomyces hansenii was obtained through xylose
      enrichment technique in a statistically optimized medium containing 0.3% yeast
      extract, 0.2% peptone, 0.03% MgSO(4) .7H(2) O along with 1% methanol. The culture
      was inoculated with 6% inoculum and incubated at 30 degrees C and 250 rpm. A
      yield of 0.6 gg(-1) was obtained with a xylitol volumetric productivity of 0.65
      g/L h(-1) in the presence of 200 gL(-1) of xylose although up to 300 gL(-1) of
      xylose could be tolerated through batch fermentation. Through this technique,
      even higher concentrations of xylose as substrate could be potentially utilized
      for maximum xylitol production.

PMID- 22961754
TI  - Quantitative structure--plasma protein binding relationships of acidic drugs.
AB  - One of the most important factors, affecting significantly the overall
      pharmacokinetic and pharmacodynamic profile of a drug, is its binding to plasma
      protein (PPB). In the present study, we focus on a set of 132 diverse acidic
      drugs binding to plasma proteins to different extent and develop quantitative
      structure-plasma protein binding relationships (QSPPBR) to predict their unbound
      fraction in plasma (f(u)) using 178 molecular descriptors. QSPPBR models were
      derived after variable selection by genetic algorithm followed by stepwise
      regression and tested by cross- and external validation. The final model has r(2)
      value of 0.771, q(2) value of 0.737, and four outliers. It predicts 57% of the
      f(u) values with less than twofold error. According to the molecular descriptors
      selected as the most predictive for PPB, the lipophilicity of the drugs, the
      presence of aromatic rings, cyano groups, and H-bond donor-acceptor pairs
      increase the PPB, whereas the presence of tertiary carbon atoms, four-member
      rings, and iodine atoms decrease PPB. These descriptors were summarized into a
      short seven-item checklist of criteria responsible for PPB. The checklist could
      be used as a guide for evaluation of PPB of acidic drug candidates, similarly to
      the Lipinski's rule of five used for evaluation of oral permeability of drugs.

PMID- 22961755
TI  - TRAIL but not FasL and TNFalpha, regulates IL-33 expression in murine hepatocytes
      during acute hepatitis.
AB  - Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates
      with acute hepatitis and chronic liver failure in mice and humans. IL-33 is
      expressed in hepatocytes and is regulated by natural killer T (NKT) cells during
      concanavalin A (ConA)-induced acute liver injury. Here, we investigated the
      molecular mechanisms underlying the expression of IL-33 during acute hepatitis.
      The expression of IL-33 and its regulation by death receptor pathways was
      investigated after the induction of ConA-acute hepatitis in wildtype (WT),
      perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(
      /-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of
      acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor
      necrosis factor alpha (TNFalpha) in WT mice. Finally, the effect of TRAIL on IL
      33 expression was assessed in primary cultured murine hepatocytes. We show that
      IL-33 expression in hepatocytes is partially controlled by perforin during acute
      liver injury, but not by TNFalpha or Fas ligand (FasL). Interestingly, the
      expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in
      TRAIL-deficient mice compared to WT mice. In contrast, administration of
      recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or
      in vitro stimulation of murine hepatocytes by TRAIL but not by TNFalpha or Jo2
      induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more
      severe ConA liver injury than WT controls, suggesting a protective effect of IL
      33 in ConA-hepatitis. CONCLUSION: The expression of IL-33 during acute hepatitis
      is dependent on TRAIL, but not on FasL or TNFalpha.

PMID- 22961756
TI  - Perioperative processes and outcomes after implementation of a hospitalist-run
      preoperative clinic.
AB  - BACKGROUND: A structured, medical preoperative evaluation may positively impact
      the perioperative course of medically complex patients. Hospitalists are in a
      unique position to assist in preoperative evaluations, given their expertise with
      inpatient medicine and postoperative surgical consultation. OBJECTIVE: To
      evaluate specific outcomes after addition of a Hospitalist-run, medical
      Preoperative clinic to the standard Anesthesia preoperative evaluation. DESIGN,
      SETTING, PATIENTS: A pre/post retrospective, comparative review of outcomes of
      5223 noncardiac surgical patients at a tertiary care Veterans Administration (VA)
      medical center. RESULTS: Length of stay was reduced for inpatients with an
      American Society of Anesthesia (ASA) score of 3 or higher (P < 0.0001). There was
      a trend towards a reduction in same-day, medically avoidable surgical
      cancellations (8.5% vs 4.9%, P = 0.065). More perioperative beta blockers were
      used (P < 0.0001) and more stress tests were ordered (P = 0.012). Inpatient
      mortality rates were reduced (1.27% vs 0.36%, P = 0.0158). CONCLUSION: A
      structured medical preoperative evaluation may benefit medically complex patients
      and improve perioperative processes and outcomes.

PMID- 22961757
TI  - Depressive symptoms and frailty.
AB  - BACKGROUND: Frailty and depressive symptoms are common issues facing older adults
      and may be associated. OBJECTIVES: To determine if: (i) depressive symptoms are
      associated with frailty; (ii) there is a gradient in this effect across the range
      of depressive symptoms; and (iii) the association between depressive symptoms and
      frailty is specific to particular types of depressive symptoms (positive affect,
      negative affect, somatic complaints, and interpersonal relations). METHOD:
      Secondary analysis of an existing population-based study was conducted.
      POPULATION: In 1991, 1751 community-living adults aged 65+ years were
      interviewed. MEASURES: Depressive symptoms were measured using the Center for
      Epidemiologic Studies-Depression (CES-D) scale. Frailty was graded from 0 (no
      frailty) to 3 (moderate/severe frailty). Age, gender, education, marital status,
      self-rated health, and the number of comorbid conditions were self-reported.
      ANALYSES: Logistic regression models were constructed with the outcome of no
      frailty/urinary incontinence only versus frailty. RESULTS: Depressive symptoms
      were strongly associated with frailty, and there was a gradient effect across the
      entire range of the CES-D scale. The odds ratio and 95% confidence interval was
      1.08 (1.06, 1.09) per point of the CES-D in unadjusted models. After potential
      confounding factors were adjusted, the adjusted odds ratio (95% confidence
      interval) was 1.03 (1.01, 1.05). Positive affect, negative affect, and somatic
      complaints were all associated with frailty, whereas interpersonal relations were
      not associated with frailty. CONCLUSIONS: Depressive symptoms are associated with
      frailty. Clinicians should consider assessing frail older adults for the presence
      of depression.

PMID- 22961758
TI  - High antitumor activity of highly resistant salan-titanium(IV) complexes in
      nanoparticles: an identified active species.
AB  - A nanoformulated trinuclear hydrolysis product of a bis(alkoxo) salan-Ti(IV) 
      complex shows high antitumor activity, which identifies it as an active species
      in cells. Additional highly stable mononuclear derivatives also show high
      activity, when formulated into nanoparticles, thus evincing that biologically
      friendly Ti(IV)  can provide high cytotoxicity with controlled biological
      function.

PMID- 22961759
TI  - Advances in chromatographic supports for pharmaceutical-grade plasmid DNA
      purification.
AB  - Chromatographic technology is undoubtedly one of the most diverse and powerful
      purification methods for downstream process applications. The diversity and
      quantity of biomolecules present in crude extracts as well as the similarities
      between impurities and the target biomolecule are considered the critical
      challenges in the extraction and purification steps. Thus, it is important to
      optimize the purification protocol to achieve maximum recovery of the target
      sample. The structure of chromatographic supports has been continuously developed
      to afford rapid and efficient separations, as well as, the application of
      specific ligands to improve the selectivity for the target molecule. The present
      review discusses the structural progress and evolution of the chromatographic
      supports that have been used for plasmid DNA purification. Nowadays, the most
      desirable form of plasmid for gene therapy and DNA vaccination is the supercoiled
      isoform, due to its stability and higher transfection efficiency over other
      plasmid topologies. However, the main challenge is not only to produce high
      quantities of supercoiled plasmid DNA but also to preserve its quality, meeting
      the strict requirements recommended by the regulatory agencies. Therefore, this
      review will focus on the chemical and structural classification of the different
      media and on some of the specific ligands used for plasmid DNA bioseparation.

PMID- 22961760
TI  - Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects
      glycemic control and mitochondrial function.
AB  - The histidine triad nucleotide-binding (HINT2) protein is a mitochondrial
      adenosine phosphoramidase expressed in the liver and pancreas. Its physiological
      function is unknown. To elucidate the role of HINT2 in liver physiology, the
      mouse Hint2 gene was deleted. Hint2(-/-) and Hint2(+/+) mice were generated in a
      mixed C57Bl6/J * 129Sv background. At 20 weeks, the phenotypic changes in Hint2(
      /-) relative to Hint2(+/+) mice were an accumulation of hepatic triglycerides,
      decreased tolerance to glucose, a defective counter-regulatory response to
      insulin-provoked hypoglycemia, and an increase in plasma interprandial insulin
      but a decrease in glucose-stimulated insulin secretion and defective
      thermoregulation upon fasting. Leptin messenger RNA (mRNA) in adipose tissue and
      plasma leptin were elevated. In mitochondria from Hint2(-/-) hepatocytes, state 3
      respiration was decreased, a finding confirmed in HepG2 cells where HINT2 mRNA
      was silenced. The linked complex II-III electron transfer was decreased in Hint2(
      /-) mitochondria, which was accompanied by a lower content of coenzyme Q. Hypoxia
      inducible factor-2alpha expression and the generation of reactive oxygen species
      were increased. Electron microscopy of mitochondria in Hint2(-/-) mice aged 12
      months revealed clustered, fused organelles. The hepatic activities of 3
      hydroxyacyl-coenzyme A dehydrogenase short chain and glutamate dehydrogenase
      (GDH) were decreased by 68% and 60%, respectively, without a change in protein
      expression. GDH activity was similarly decreased in HINT2-silenced HepG2 cells.
      When measured in the presence of purified sirtuin 3, latent GDH activity was
      recovered (126% in Hint2(-/-) versus 83% in Hint2(+/+) ). This suggests a greater
      extent of acetylation in Hint2(-/-) than in Hint2(+/+) . CONCLUSION: Hint2/HINT2
      positively regulates mitochondrial lipid metabolism and respiration and glucose
      homeostasis. The absence of Hint2 provokes mitochondrial deformities and a change
      in the pattern of acetylation of selected proteins.

PMID- 22961761
TI  - Embryonic stem cell-derived neural stem cells fuse with microglia and mature
      neurons.
AB  - Transplantation of neural stem cells (NSCs) is a novel strategy to restore
      function in the diseased brain, acting through multiple mechanisms, for example,
      neuronal replacement, neuroprotection, and modulation of inflammation. Whether
      transplanted NSCs can operate by fusing with microglial cells or mature neurons
      is largely unknown. Here, we have studied the interaction of a mouse embryonic
      stem cell-derived neural stem (NS) cell line with rat and mouse microglia and
      neurons in vitro and in vivo. We show that NS cells spontaneously fuse with
      cocultured cortical neurons, and that this process requires the presence of
      microglia. Our in vitro data indicate that the NS cells can first fuse with
      microglia and then with neurons. The fused NS/microglial cells express markers
      and retain genetic and functional characteristics of both parental cell types,
      being able to respond to microglia-specific stimuli (LPS and IL-4/IL-13) and to
      differentiate to neurons and astrocytes. The NS cells fuse with microglia, at
      least partly, through interaction between phosphatidylserine exposed on the
      surface of NS cells and CD36 receptor on microglia. Transplantation of NS cells
      into rodent cortex results in fusion with mature pyramidal neurons, which often
      carry two nuclei, a process probably mediated by microglia. The fusogenic role of
      microglia could be even more important after NSC transplantation into brains
      affected by neurodegenerative diseases associated with microglia activation. It
      remains to be elucidated how the occurrence of the fused cells will influence the
      functional outcome after NSC transplantation in the diseased brain.

PMID- 22961762
TI  - beta2 and gamma3 laminins are critical cortical basement membrane components:
      ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces
      dysplasia.
AB  - Cortical development is dependent on the timely production and migration of
      neurons from neurogenic sites to their mature positions. Mutations in several
      receptors for extracellular matrix (ECM) molecules and their downstream signaling
      cascades produce dysplasia in brain. Although mutation of a critical binding site
      in the gene that encodes the ECM molecule laminin gamma1 (Lamc1) disrupts
      cortical lamination, the ECM ligand(s) for many ECM receptors have not been
      demonstrated directly in the cortex. Several isoforms of the heterotrimeric
      laminins, all containing the beta2 and gamma3 chain, have been isolated from the
      brain, suggesting they are important for CNS function. Here, we report that mice
      homozygous null for the laminin beta2 and gamma3 chains exhibit cortical laminar
      disorganization. Mice lacking both of these laminin chains exhibit hallmarks of
      human cobblestone lissencephaly (type II, nonclassical): they demonstrate severe
      laminar disruption; midline fusion; perturbation of Cajal-Retzius cell
      distribution; altered radial glial cell morphology; and ectopic germinal zones.
      Surprisingly, heterozygous mice also exhibit laminar disruption of cortical
      neurons, albeit with lesser severity. In compound null mice, the pial basement
      membrane is fractured, and the distribution of a key laminin receptor,
      dystroglycan, is altered. These data suggest that beta2 and gamma3-containing
      laminins play an important dose-dependent role in development of the cortical
      pial basement membrane, which serves as an attachment site for Cajal-Retzius and
      radial glial cells, thereby guiding neural development.

PMID- 22961763
TI  - BIRC5 expression is a poor prognostic marker in Ewing sarcoma.
AB  - BACKGROUND: BIRC5 (Survivin), an inhibitor of apoptosis protein (IAP), is over
      expressed in several human cancers and increased expression is associated with
      poor prognosis. The goal of the current study was to evaluate the role of BIRC5
      in Ewing sarcoma (ES), the second most common pediatric bone sarcoma. PROCEDURE:
      BIRC5 protein expression was determined in ES cell lines using Western Blot
      analysis. Functional role of survivin on growth and viability of ES cells was
      assessed by siRNA knockdown of BIRC5 and by using a small molecule inhibitor
      YM155. Immunohistochemical analysis for BIRC5 protein was performed on patient
      tumor samples using an anti-survivin antibody. The degree of BIRC5 protein
      expression was correlated with clinical parameters and patient outcome. RESULTS:
      BIRC5 is over-expressed in a panel of ES cell lines. Gene silencing of BIRC5 in
      the ES cell line TC-71 decreases cell growth by more than 50% for each BIRC5
      siRNA construct compared to non-silencing siRNA control constructs. YM155 also
      reduces ES cell growth and viability with an EC(50) ranging from 2.8 to 6.2 nM.
      BIRC5 protein is expressed in majority of the ES tumor samples with minimal
      expression in normal tissue (P < 0.005). Tumors with more than 50% expression are
      associated with worse overall survival than tumors with less than 50% expression
      (Hazard Ratio: 6.05; CI: 1.7-21.4; P = 0.04). CONCLUSION: BIRC5 is over-expressed
      in ES cell lines and tumor samples. Further, it plays an important role in cell
      growth and viability in vitro. Higher degree of expression in patients is an
      independent poor prognostic factor.

PMID- 22961764
TI  - Polymers with upper critical solution temperature in aqueous solution.
AB  - This review focuses on polymers with upper critical solution temperature (UCST)
      in water or electrolyte solution and provides a detailed survey of the yet few
      existing examples. A guide for synthetic chemists for the design of novel UCST
      polymers is presented and possible handles to tune the phase transition
      temperature, sharpness of transition, hysteresis, and effectiveness of phase
      separation are discussed. This review tries to answer the question why polymers
      with UCST remained largely underrepresented in academic as well as applied
      research and what requirements have to be fulfilled to make these polymers
      suitable for the development of smart materials with a positive thermoresponse.

PMID- 22961765
TI  - Stereoselective iodolactonization of 4-allenoic acids with efficient chirality
      transfer: development of a new electrophilic iodination reagent.
AB  - A highly stereoselective iodolactonization of 4-allenoic acids with a new
      sterically demanding electrophilic iodination reagent to afford optically active
      gamma-butyrolactones has been developed. The reaction shows high efficiency of
      axial chirality transfer and excellent Z/E selectivity and has been applied to
      the synthesis of chiral cis-beta,gamma-disubstituted gamma-butyrolactones to give
      very high diastereomeric and enantiomeric excess values. The reaction has been
      successfully utilized in the synthesis of naturally occurring compounds (+)-cis
      whisky lactone and (+)-cis-3-methyl-4-decanolide.

PMID- 22961768
TI  - Simultaneous production of alkaline lipase and protease by antibiotic and heavy
      metal tolerant Pseudomonas aeruginosa.
AB  - An efficient bacterial strain capable of simultaneous production of lipase and
      protease in a single production medium was isolated. Thirty six bacterial
      strains, isolated from diverse habitats, were screened for their lipolytic and
      proteolytic activity. Of these, only one bacterial strain was found to be lipase
      and protease producer. The 16S rDNA sequencing and phylogenetic analyses revealed
      that strain (NSD-09) was in close identity to Pseudomonas aeruginosa. The maximum
      lipase (221.4 U/ml) and protease (187.9 U/ml) activities were obtained after 28
      and 24 h of incubation, respectively at pH 9.0 and 37  degrees C. Castor oil and
      wheat bran were found to be the best substrate for lipase and protease
      production, respectively. The strain also exhibited high tolerance to lead (1450
      ug/ml) and chromium (1000 ug/ml) in agar plates. It also showed tolerance to
      other heavy metals, such as Co(+2) , Zn(+2) , Hg(+2) , Ni(+2) and Cd(+2) .
      Therefore, this strain has scope for tailing bioremediation. Presumably, this is
      the first attempt on P. aeruginosa to explore its potential for both industrial
      and environmental applications. 

PMID- 22961769
TI  - MicroRNA-mediated somatic cell reprogramming.
AB  - Since the first report of induced pluripotent stem cells (iPSCs) using somatic
      cell nuclear transfer (SCNT), much focus has been placed on iPSCs due to their
      great therapeutic potential for diseases such as abnormal development,
      degenerative disorders, and even cancers. Subsequently, Takahashi and Yamanaka
      took a novel approach by using four defined transcription factors to generate
      iPSCs in mice and human fibroblast cells. Scientists have since been trying to
      refine or develop better approaches to reprogramming, either by using different
      combinations of transcription factors or delivery methods. However, recent
      reports showed that the microRNA expression pattern plays a crucial role in
      somatic cell reprogramming and ectopic introduction of embryonic stem cell
      specific microRNAs revert cells back to an ESC-like state, although, the exact
      mechanism underlying this effect remains unclear. This review describes recent
      work that has focused on microRNA-mediated approaches to somatic cell
      reprogramming as well as some of the pros and cons to these approaches and a
      possible mechanism of action. Based on the pivotal role of microRNAs in
      embryogenesis and somatic cell reprogramming, studies in this area must continue
      in order to gain a better understanding of the role of microRNAs in stem cells
      regulation and activity.

PMID- 22961771
TI  - Maternal and offspring dopamine D4 receptor genotypes interact to influence
      juvenile impulsivity in vervet monkeys.
AB  - The merging of psychological and genetic methodologies has led to an increasing
      appreciation of environmental moderators of the relationships between genotype
      and phenotype. Here we used a nonhuman-primate model to study the moderating
      effect of the mother's genotype on the association of a dopamine D4 receptor
      (DRD4) gene polymorphism with juvenile impulsivity, assessed in a standardized
      social-challenge test. The results showed that juvenile carriers of the rare 5
      repeat variant of the exon III 48-base-pair repeat polymorphism scored
      significantly higher in social impulsivity than juveniles homozygous for the
      common 6-repeat allele. In addition, juvenile genotype interacted with maternal
      genotype to influence impulsivity, with the highest rates of impulsivity found in
      variant offspring with variant mothers. These results highlight the importance of
      considering the genotype of the parents in studies of early experience and
      vulnerability genes for impulsivity-related traits.

PMID- 22961772
TI  - The Stranger effect: the rejection of affective deviants.
AB  - What happens when affective displays deviate from normative expectations? In this
      study, participants evaluated target individuals displaying flat, incongruent, or
      congruent expressions seemingly in response to pictures eliciting positive,
      neutral, or negative affect. Relative to targets who displayed normative
      reactions, those who violated affective norms (affective deviants) were rated
      more negatively on various dimensions of social judgment. Participants also
      preferred greater social distance from affective deviants, reported more moral
      outrage in response to them, and inferred that these targets did not share their
      moral values. Incongruent affect resulted in more negative social judgment than
      did flat affect, and this relationship was moderated by stimulus valence.
      Finally, the relationship between targets' affective expressions and
      participants' avoidant intentions was mediated by the extent to which
      participants thought the targets shared their moral values. These findings
      demonstrate the interpersonal costs of affective deviance, revealing the
      pervasiveness and force of affective norms.

PMID- 22961770
TI  - Roles of hepatocyte and myeloid CXC chemokine receptor-2 in liver recovery and
      regeneration after ischemia/reperfusion in mice.
AB  - Previous studies have demonstrated the significance of signaling through the CXC
      chemokine receptor-2 (CXCR2) receptor in the process of recovery and regeneration
      of functional liver mass after hepatic ischemia/reperfusion (I/R). CXCR2 is
      constitutively expressed on both neutrophils and hepatocytes; however, the cell
      specific roles of this receptor are unknown. In the present study, chimeric mice
      were created through bone marrow transplantation (BMT) using wild-type and CXCR2
      knockout mice, yielding selective expression of CXCR2 on hepatocytes (Hep) and/or
      myeloid cells (My) in the following combinations: Hep+/My+; Hep-/My+; Hep+/My-;
      and Hep-/My-. These tools allowed us to assess the contributions of myeloid and
      hepatocyte CXCR2 in the recovery of the liver after I/R injury. Flow cytometry
      confirmed the adoption of the donor phenotype in neutrophils. Interestingly,
      Kupffer cells from all chimeras lacked CXCR2 expression. Recovery/regeneration of
      hepatic parenchyma was assessed by histologic assessment and measurement of
      hepatocyte proliferation. CXCR2(Hep+/My+) mice showed the least amount of liver
      recovery and hepatocyte proliferation, whereas CXCR2(Hep-/My-) mice had the
      greatest liver recovery and hepatocyte proliferation. CXCR2(Hep+/My-) mice had
      enhanced liver recovery, with hepatocyte proliferation similar to CXCR2(Hep-/My-)
      mice. Myeloid expression of CXCR2 directly regulated CXC chemokine expression
      levels after hepatic I/R, such that mice lacking myeloid CXCR2 had markedly
      increased chemokine expression, compared with mice expressing CXCR2 on myeloid
      cells. CONCLUSION: The data suggest that CXCR2 on myeloid cells is the
      predominant regulator of liver recovery and regeneration after I/R injury,
      whereas hepatocyte CXCR2 plays a minor, secondary role. These findings suggest
      that myeloid cell-directed therapy may significantly affect liver regeneration
      after liver resection or transplantation.

PMID- 22961773
TI  - A time-based account of the perception of odor objects and valences.
AB  - Is human odor perception guided by memory or emotion? Object-centered accounts
      predict that recognition of unique odor qualities precedes valence decoding.
      Valence-centered accounts predict the opposite: that stimulus-driven valence
      responses precede and guide identification. In a speeded response time study,
      participants smelled paired odors, presented sequentially, and indicated whether
      the second odor in each pair belonged to the same category as the first (object
      evaluation task) or whether the second odor was more pleasant than the first
      (valence evaluation task). Object evaluation was faster and more accurate than
      valence evaluation. In a complementary experiment, participants performed an
      identification task, in which they indicated whether an odor matched the
      previously presented word label. Responses were quicker for odors preceded by
      semantically matching, rather than nonmatching, word labels, but results showed
      no evidence of interference from valence on nonmatching trials. These results are
      in accordance with object-centered accounts of odor perception.

PMID- 22961774
TI  - Assessment of teamwork during structured interdisciplinary rounds on medical
      units.
AB  - BACKGROUND: Interdisciplinary rounds (IDR) provide a means to assemble hospital
      team members and improve collaboration. Little is known about teamwork during
      IDR. OBJECTIVE: To evaluate and characterize teamwork during IDR. DESIGN: Cross
      sectional observational study. SETTING: Six medical units which had implemented
      structured interdisciplinary rounds (SIDR). MEASUREMENTS: We adapted the
      Observational Teamwork Assessment for Surgery (OTAS) tool, a behaviorally
      anchored rating scale shown to be reliable and valid in surgical settings. OTAS
      provides scores ranging from 0 to 6 (0 = problematic behavior; 6 = exemplary
      behavior) across 5 domains (communication, coordination, cooperation/backup
      behavior, leadership, and monitoring/situational awareness) and for prespecified
      subteams. Two researchers conducted direct observations using the adapted OTAS
      tool. RESULTS: We conducted 7-8 independent observations for each unit (total =
      44) and 20 joint observations. Inter-rater reliability was excellent at the unit
      level (Spearman's rho = 0.75), and good across domains (rho = 0.53-0.68) and
      subteams (rho = 0.53-0.76) with the exception of the physician subteam, for which
      it was poor (rho = 0.35). Though teamwork scores were generally high, we found
      differences across units, with a median (interquartile range [IQR]) 4.5 (3.9-4.9)
      for the lowest and 5.4 (5.3-5.5) for the highest performing unit (P < 0.01).
      Domain scores differed, with leadership receiving the lowest (median [IQR] = 5.0
      [4.6-5.3]), and cooperation/backup behavior and monitoring/situational awareness
      receiving highest scores (median [IQR] = 5.4 [5.0-5.5] and 5.4 [5.0-5.7]).
      Differences across subteams were of borderline significance (P = 0.05).
      CONCLUSIONS: The adapted OTAS instrument demonstrated acceptable reliability for
      assessing teamwork during SIDR across units, domains, and most subteams.
      Variation in performance suggests a need to improve consistency of teamwork and
      emphasizes the importance of leadership.

PMID- 22961776
TI  - Intervening to reduce the future burden of occupational cancer in britain: what
      could work?
AB  - In Britain, 14 carcinogenic agents and occupational circumstances currently
      account for 86% of estimated occupation attributable cancer. The future burden
      associated with these carcinogens has been forecast, using attributable fractions
      for forecast scenarios representing patterns of past and predicted future
      exposure, and exposure levels representing the introduction of new occupational
      exposure limits, increased levels of compliance with these limits and other
      reductions in worker exposure. Without intervention, occupational attributable
      cancers are forecast to remain at more than 10,000 by 2060. With modest
      intervention over 2,600, or with stricter interventions more than 8,200 cancers
      could be avoided by 2060 although because of long latency no impact will be seen
      until at least 10 years after intervention. Effective interventions assessed in
      this study include reducing workplace exposure limits and improving compliance
      with these limits. Cancers associated with asbestos, diesel engine exhaust,
      polycyclic aromatic hydrocarbons, work as a painter, radon, and solar radiation
      are forecast to continue, with construction remaining the prime industry of
      concern. Although exposure levels to the established carcinogens are falling,
      workers are remaining exposed at low levels at which there is still a cancer
      risk, although the aging population also contributes to rising cancer numbers,
      These forecasts can be used to assess the relative costs to society of different
      occupational carcinogenic agents, and the relative merits and savings associated
      with alternative intervention strategies. The methods are adaptable for different
      data circumstances, other types of interventions and could be extended to
      environmental carcinogens and other chronic diseases.

PMID- 22961775
TI  - Multiphoton tomographic imaging: a potential optical biopsy tool for detecting
      gastrointestinal inflammation and neoplasia.
AB  - Endoscopy is widely used to detect and remove premalignant lesions with the goal
      of preventing gastrointestinal (GI) cancers. Because current endoscopes do not
      provide cellular resolution, all suspicious lesions are biopsied and subjected to
      histologic evaluation. Technologies that facilitate directed biopsies should
      decrease both procedure-related morbidity and cost. Here we explore the use of
      multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic
      tissue emissions, to evaluate pathology in both experimental and human GI
      specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues
      for comparison. After evaluating the entire normal mouse GI tract, MPM was used
      to investigate disease progression in mouse models of colitis and colorectal
      carcinogenesis. MPM provided sufficient histologic detail to identify all
      relevant substructures in ex vivo normal GI tissue, visualize both acute and
      resolving stages of colitis, and show the progression of colorectal
      carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue,
      inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally,
      colonic mucosa in live anesthetized rats was imaged in vivo using a flexible
      endoscope prototype. In both animal models and human specimens, MPM images showed
      a striking similarity to the results of H&E staining, as shown by the 100%
      concordance achieved by the study pathologists' diagnoses. In summary, MPM is a
      promising technique that accurately visualizes histology in fresh, unstained
      tissues. Our findings support the continued development of MPM as a technology to
      enhance the early detection of GI pathologies including premalignant lesions.

PMID- 22961777
TI  - Aspirin use after a prostate cancer diagnosis and cancer survival in a
      prospective cohort.
AB  - Experimental and clinical data suggest that aspirin and other nonsteroidal
      inflammatory drugs may delay the progression of prostate cancer through
      inhibition of the COX pathway and its effects on cellular proliferation,
      apoptosis, and angiogenesis. Epidemiologic data support a reduced risk of
      prostate cancer incidence with aspirin use, yet no evidence exists about whether
      aspirin after diagnosis influences progression or survival. We conducted a
      prospective study of 3,986 participants of the Health Professionals Follow-up
      Study, with a prostate cancer diagnosis between January 1, 1990, and December 31,
      2005. We used Cox proportional hazards regression to evaluate the association
      between aspirin use after diagnosis and the development of metastases or fatal
      prostate cancer through January 31, 2008, adjusting for risk factors associated
      with incidence and mortality in this cohort, prediagnostic aspirin use, Gleason
      score, tumor-node-metastasis (TNM) stage, and primary treatment. In total, 265
      men developed bony or other organ metastases or fatal prostate cancer during the
      18 years of follow-up. We observed no association between updated aspirin use
      after diagnosis and lethal prostate cancer [tablets/week: <2: HR, 1.12; 95%
      confidence interval (CI), 0.72-1.72; 2-5: HR, 1.05; 95% CI, 0.62-1.80; >= 6: HR,
      1.08; 95% CI, 0.76-1.54; P(trend) = 0.99]. The results remained unchanged when we
      examined aspirin use at baseline only (P(trend) = 0.70) or frequency of use
      (d/wk; P(trend) = 0.35) or limited the outcome to fatal prostate cancer (P(trend)
      = 0.63). There was no association between aspirin use after a prostate cancer
      diagnosis and lethal disease in this cohort of prostate cancer survivors.

PMID- 22961779
TI  - Aberrant methylation of RASGRF1 is associated with an epigenetic field defect and
      increased risk of gastric cancer.
AB  - Aberrant DNA methylation is implicated in the epigenetic field defect seen in
      gastric cancer. Our aim in this study was to identify predictive biomarkers by
      screening for DNA methylation in noncancerous background gastric mucosa from
      patients with gastric cancer. Using methylated-CpG island amplification coupled
      with CpG island microarray (MCAM) analysis, we identified 224 genes that were
      methylated in the noncancerous gastric mucosa of patients with gastric cancer.
      Among them, RASGRF1 methylation was significantly elevated in gastric mucosa from
      patients with either intestinal or diffuse type gastric cancer, as compared with
      mucosa from healthy individuals (8.3% vs. 22.4%, P < 0.001; 8.3% vs. 19.4%, P <
      0.001). RASGRF1 methylation was independent of mucosal atrophy and could be used
      to distinguish both serum pepsinogen test-positive [sensitivity, 70.0%;
      specificity, 86.7%; area under the receiver operator characteristic (ROC) curve,
      AUC, 0.763] and -negative patients with gastric cancer (sensitivity, 72.2%;
      specificity, 87.0%; AUC, 0.844) from healthy individuals. Ectopic expression of
      RASGRF1 suppressed colony formation and Matrigel invasion by gastric cancer
      cells, suggesting it may be involved in gastric tumorigenesis. Collectively, our
      data suggest that RASGRF1 methylation is significantly involved in an epigenetic
      field defect in the stomach, and that it could be a useful biomarker to identify
      individuals at high risk for gastric cancer.

PMID- 22961778
TI  - Metabolic profiling, a noninvasive approach for the detection of experimental
      colorectal neoplasia.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      United States. Although noninvasive stool-based screening tests are used for the
      early detection of colorectal neoplasia, concerns have been raised about their
      sensitivity and specificity. A metabolomics-based approach provides a potential
      noninvasive strategy to identify biomarkers of colorectal carcinogenesis
      including premalignant adenomas. Our primary objective was to determine whether a
      distinct metabolic profile could be found in both feces and plasma during
      experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and
      normal colorectal mucosa were obtained from A/J mice at several time points
      following administration of azoxymethane or saline. Ultra-performance liquid
      chromatography tandem mass spectroscopy and gas chromatography mass spectroscopy
      were used to quantify metabolites in each of these matrices. Here, we show that
      colorectal carcinogenesis was associated with significant metabolic alterations
      in both the feces and plasma, some of which overlap with metabolic changes in the
      tumor tissue. These consisted of 33 shared changes between feces and tumor, 14
      shared changes between plasma and tumor, and 3 shared changes across all 3
      matrices. For example, elevated levels of sarcosine were found in both tumor and
      feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and
      plasma. Collectively, these results provide evidence that metabolomics can be
      used to detect changes in feces and plasma during azoxymethane-induced colorectal
      carcinogenesis and thus provide a strong rationale for future studies in humans.

PMID- 22961780
TI  - Synthesis and application of vinylpyridine containing ion-imprinted copolymer gel
      microbeads for Cu(II) solid-phase extraction.
AB  - The influence of polymer matrix on the extraction efficiency for Cu(II) and
      selectivity against metal ions such as Ni(II), Cd(II), Pb(II) of Cu(II) imprinted
      copolymer gels was described. The functional monomers investigated include the
      weakly basic 4-vinylpyridine (4-VP) and its mixure with the acidic and hydrogen
      binding methacrylic acid. Copolymer gels were prepared by dispersion cross
      linking copolymerization using Cu(II)-4-(2-pyridylazo)resorcinol complex, Cu(II),
      or 4-(2-pyridylazo)resorcinol as templates. The chemical structure and morphology
      of the Cu(II)-imprinted microbeads are defined using elemental analysis, Fourier
      transform infrared spectroscopy, and scanning electron microscopy. Extraction
      efficiencies of newly synthesized sorbents were studied by batch procedure. The
      prepared copolymer gel with 4-VP as monomer and Cu(II)-4-(2-pyridylazo)resorcinol
      complex has higher capacity and selectivity toward Cu(II) than the copolymer gels
      prepared using the mixture of methacrylic acid and 4-VP. This new sorbent can be
      used as an effective SPE material for the highly selective preconcentration and
      separation of Cu(II) in sea water samples. It shows high mechanical and chemical
      stability.

PMID- 22961781
TI  - Design and characterization of a protein superagonist of IL-15 fused with IL
      15Ralpha and a high-affinity T cell receptor.
AB  - To avoid high systemic doses, strategies involving antigen-specific delivery of
      cytokine via linked antibodies or antibody fragments have been used. Targeting
      cancer-associated peptides presented by major histocompatibility complex (MHC)
      molecules (pepMHC) increases the number of potential target antigens and takes
      advantage of cross-presentation on tumor stroma and in draining lymph nodes.
      Here, we use a soluble, high-affinity single-chain T cell receptor Valpha-Vbeta
      (scTv), to deliver cytokines to intracellular tumor-associated antigens presented
      as pepMHC. As typical wild-type T cell receptors (TCRs) exhibit low affinity
      (K(d) = 1-100 MUM or more), we used an engineered TCR, m33, that binds its
      antigenic peptide SIYRYYGL (SIY) bound to the murine class I major
      histocompatability complex protein H2-K(b) (SIY/K(b) ) with nanomolar affinity
      (K(d) = 30 nM). We generated constructs consisting of m33 scTv fused to murine
      interleukin 2 (IL-2), interleukin 15 (IL-15), or IL-15/IL-15Ralpha (IL-15 linked
      to IL-15Ralpha sushi domain, called "superfusion"). The fusions were purified
      with good yields and bound specifically to SIY/K(b) with high affinity. Proper
      cytokine folding and binding were confirmed, and the fusions were capable of
      stimulating proliferation of cytokine-dependent cells, both when added directly
      and when presented in trans, bound to cells with the target pepMHC. The m33
      superfusion was particularly potent and stable and represents a promising design
      for targeted antitumor immunomodulation.

PMID- 22961783
TI  - Multisystem physiological dysfunction is associated with depressive symptoms in a
      population-based sample of older adults.
AB  - OBJECTIVE: To evaluate the association between multisystem physiological
      dysfunction and depressive symptom severity in the US older adults. METHODS: We
      examined 2405 adults of age 60 years and older by using the data from the 2005
      2008 National Health and Nutrition Examination Survey. We constructed a summary
      score of "physiological dysfunction," encompassing cardiovascular function,
      glucose regulation, liver function, and renal function. Overall depressive
      symptoms were obtained from the 9-item Patient Health Questionnaire depression
      scale, and factor analysis was used to derive affective and somatic symptom
      scores. We employed multiple linear regression models to estimate associations
      between physiological dysfunction scores and affective, somatic, and overall
      depressive symptoms, while adjusting for demographic, socioeconomic factors, and
      other potentially confounding factors. RESULTS: Greater multisystem physiological
      dysfunction scores were associated with an increased severity of overall,
      affective, and somatic depressive symptoms. These associations persisted after
      adjusting for all covariates: beta = 0.23 (95% confidence interval (CI) = 0.13,
      0.32); beta = 0.08 (95% CI = 0.04, 0.11); beta = 0.12 (95% CI = 0.06, 0.18),
      respectively. CONCLUSIONS: Our results suggest that the multisystem physiological
      dysfunction is associated with late-life depressive symptoms. Additional
      longitudinal studies of links between allostatic load, psychosocial stress events
      throughout the life course, and late-life depressive symptoms may shed further
      light on this association.

PMID- 22961784
TI  - No evidence of increased asparagine levels in the bone marrow of patients with
      acute lymphoblastic leukemia during asparaginase therapy.
AB  - BACKGROUND: Mesenchymal cells (MSCs) in bone marrow (BM) may produce asparagine
      and form protective niches for leukemic cells. In vitro, this led to high levels
      of asparagine and conferred asparaginase resistance to acute lymphoblastic
      leukemia (ALL) cells. The aim of this study was to investigate whether MSCs or
      other cells in BM indeed produce such significant amounts of asparagine in vivo
      as to result in clinical asparaginase resistance. PROCEDURE: Twenty-six patients
      with newly diagnosed ALL were enrolled. All children received induction
      chemotherapy according to the Dutch Childhood Oncology Group (DCOG) ALL-10
      protocol. Asparaginase was administered from days 12-33. Asparaginase,
      asparagine, aspartic acid, glutamine, and glutamic acid levels were measured in
      BM and blood at diagnosis, days 15, 33, and 79. RESULTS: Median asparaginase
      trough levels were not significantly different at days 15 and 33. Only at
      diagnosis, asparagine level was significantly higher in BM than in blood (P =
      0.001). Asparagine levels were all below the lower limit of quantification in BM
      and blood at days 15 and 33. However, aspartic acid level in BM was significantly
      higher than in blood (P < 0.001) at diagnosis, and also at days 15, 33, and 79.
      CONCLUSIONS: We demonstrate higher aspartic acid levels in BM compared to blood;
      however, no increased asparagine levels were seen during induction therapy
      containing asparaginase in BM when compared to blood. Therefore, increased
      asparagine synthesis by MSCs is of relevance for resistance to asparaginase of
      leukemic cells in vitro, but it is questionable whether this leads to
      asparaginase resistance in childhood ALL patients.

PMID- 22961785
TI  - Free SBV tests for cattle and sheep imported to Scotland.

PMID- 22961786
TI  - Registration of veterinary pharmacies.

PMID- 22961789
TI  - Welfare advisory council sets out standards for dog breeders.

PMID- 22961790
TI  - Taking forward 'a refreshed RCVS'.

PMID- 22961793
TI  - Bovine fetal abnormalities continue to be detected in June.

PMID- 22961794
TI  - Repairing nictitans gland prolapse in dogs.

PMID- 22961796
TI  - Trichomonosis in finches in Slovenia.

PMID- 22961798
TI  - Lentivirus-mediated RNAi knockdown of NUPR1 inhibits human nonsmall cell lung
      cancer growth in vitro and in vivo.
AB  - NUPR1 (nuclear protein 1) was found to play a key role in the development of
      several malignancies including pancreas, breast, and prostate cancers. However,
      the functional role of NUPR1 in nonsmall cell lung cancer (NSCLC) progression and
      development is little known. Here, lentivirus-mediated small interfering RNA
      (siRNA) was employed to downregulate endogenous NUPR1 expression to study the
      function of NUPR1 in growth of nonsmall cell lung cancer. A lentivirus-mediated
      RNAi technology was used to specifically knock down the expression of NUPR1 in
      H1299 cells. Quantitative real-time reverse transcriptase polymerase chain
      reaction, flow cytometry, western blot and cell count assays were studied to
      characterize NUPR1 expression in vitro. Furthermore, nonsmall cell lung cancer
      xenograft models in nude mice were established to investigate whether knockdown
      of NUPR1 reduces the tumor growth in vivo. We found that downregulation of NUPR1
      expression significantly inhibited nonsmall cell lung cancer H1299 cells
      proliferation and colony formation in vitro. Moreover, the specific
      downregulation of NUPR1 arrested cells in G0 phase of cell cycle and increased
      apoptosis rate. Silencing of NUPR1 also suppressed tumor growth by tail vein
      injection of lentivirus encoded shRNA against NUPR1 in vivo. Our findings
      revealed that the NUPR1 gene represents a promising target for gene silencing
      therapy in nonsmall cell lung cancer.

PMID- 22961799
TI  - Removal of 2,4,5-trichlorophenol by bacterial isolates from the secondary sludge
      of pulp and paper mill.
AB  - 2,4,5-trichlorophenol (2,4,5-TCP) mineralizing bacteria were isolated from the
      secondary sludge of pulp and paper industry. These isolates used 2,4,5-TCP as a
      source of carbon and energy and were capable of degrading this compound, as
      indicated by stoichimetric release of chloride and biomass formation. Based on
      16S rRNA sequence analysis, these bacteria were identified as Kocuria sp. (CL2),
      Bacillus pumillus (CL5), Pseudomonas stutzeri (CL7). HPLC analysis revealed that
      these isolates were able to degrade 2,4,5-TCP at higher concentrations (600 mg/l
      or 3.0 mM). A consortia of these isolates completely removed 2,4,5-TCP from the
      sludge obtained from pulp and paper mill within 2 weeks when supplemented at a
      rate of 100 mg l(-1) . Bacterial consortium also significantly reduced absorbable
      organic halogen (AOX) and extractable organic halogen (EOX) by 61% and 63%,
      respectively from the sludge. These isolates have high potential to remove 2,4,5
      TCP and may be used for remediation of pulp paper mill waste containing 2,4,5
      TCP. 

PMID- 22961800
TI  - Advances in cholangiocyte immunobiology.
AB  - Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining
      of the conduit system comprising the intra- and extrahepatic bile ducts. Growing
      experimental evidence demonstrated that cholangiocytes are in fact the first line
      of defense of the biliary system against foreign substances. Experimental
      advances in recent years have unveiled previously unknown roles of cholangiocytes
      in both innate and adaptive immune responses. Cholangiocytes can release
      inflammatory modulators in a regulated fashion. Moreover, they express
      specialized pattern-recognizing molecules that identify microbial components and
      activate intracellular signaling cascades leading to a variety of downstream
      responses. The cytokines secreted by cholangiocytes, in conjunction with the
      adhesion molecules expressed on their surface, play a role in recruitment,
      localization, and modulation of immune responses in the liver and biliary tract.
      Cholangiocyte survival and function is further modulated by cytokines and
      inflammatory mediators secreted by immune cells and cholangiocytes themselves.
      Because cholangiocytes act as professional APCs via expression of major
      histocompatibility complex antigens and secrete antimicrobial peptides in bile,
      their role in response to biliary infection is critical. Finally, because
      cholangiocytes release mediators critical to myofibroblastic differentiation of
      portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in
      the pathogenesis of biliary cirrhosis.

PMID- 22961801
TI  - Insights from a novel model of slow-transit constipation generated by partial
      outlet obstruction in the murine large intestine.
AB  - The mechanisms underlying slow-transit constipation (STC) are unclear. In 50% of
      patients with STC, some form of outlet obstruction has been reported; also an
      elongated colon has been linked to patients with STC. Our aims were 1) to develop
      a murine model of STC induced by partial outlet obstruction and 2) to determine
      whether this leads to colonic elongation and, consequently, activation of the
      inhibitory "occult reflex," which may contribute to STC in humans. Using a purse
      string suture, we physically reduced the maximal anal sphincter opening in
      C57BL/6 mice. After 4 days, the mice were euthanized (acutely obstructed), the
      suture was removed (relieved), or the suture was removed and replaced repeatedly
      (chronically obstructed, over 24-31 days). In partially obstructed mice, we
      observed increased cyclooxygenase (COX)-2 levels in muscularis and mucosa, an
      elongated impacted large bowel, slowed transit, nonpropagating colonic migrating
      motor complexes (CMMCs), a lack of mucosal reflexes, a depolarized circular
      muscle with slow-wave activity due to a lack of spontaneous inhibitory junction
      potentials, muscle hypertrophy, and CMMCs in mucosa-free preparations. Elongation
      of the empty obstructed colon produced a pronounced occult reflex. Removal of the
      obstruction or addition of a COX-2 antagonist (in vitro and in vivo) restored
      membrane potential, spontaneous inhibitory junction potentials, CMMC propagation,
      and mucosal reflexes. We conclude that partial outlet obstruction increases COX-2
      leading to a hyperexcitable colon. This hyperexcitability is largely due to
      suppression of only descending inhibitory nerve pathways by prostaglandins. The
      upregulation of motility is suppressed by the occult reflex activated by colonic
      elongation.

PMID- 22961803
TI  - Mechanism of protection of transepithelial barrier function by Lactobacillus
      salivarius: strain dependence and attenuation by bacteriocin production.
AB  - Enhanced barrier function is one mechanism whereby commensals and probiotic
      bacteria limit translocation of foreign antigens or pathogens in the gut.
      However, barrier protection is not exhibited by all probiotic or commensals and
      the strain-specific molecules involved remain to be clarified. We evaluated the
      effects of 33 individual Lactobacillus salivarius strains on the hydrogen
      peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells.
      These strains showed markedly different effects on H(2)O(2)-induced reduction in
      transepithelial resistance (TER). The effective strains such as UCC118 and
      CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight
      junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and
      CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK)
      in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting
      effect of these strains. In contrast, the AH43324 strain induced phosphorylation
      of Akt and p38, which was associated with an absence of a protective effect.
      Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a
      bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions.
      A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive
      effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The
      wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38,
      whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate
      that L. salivarius strains are widely divergent in their capacity for barrier
      protection, and this is underpinned by differences in the activation of
      intracellular signaling pathways. Furthermore, bacteriocin production appears to
      have an attenuating influence on lactobacillus-mediated barrier protection.

PMID- 22961802
TI  - Autophagy and pancreatitis.
AB  - Acute pancreatitis is an inflammatory disease of the exocrine pancreas that
      carries considerable morbidity and mortality; its pathophysiology remains poorly
      understood. Recent findings from experimental models and genetically altered mice
      summarized in this review reveal that autophagy, the principal cellular
      degradative pathway, is impaired in pancreatitis and that one cause of autophagy
      impairment is defective function of lysosomes. We propose that the
      lysosomal/autophagic dysfunction is a key initiating event in pancreatitis and a
      converging point of multiple deranged pathways. There is strong evidence
      supporting this hypothesis. Investigation of autophagy in pancreatitis has just
      started, and many questions about the "upstream" mechanisms mediating the
      lysosomal/autophagic dysfunction and the "downstream" links to pancreatitis
      pathologies need to be explored. Answers to these questions should provide
      insight into novel molecular targets and therapeutic strategies for treatment of
      pancreatitis.

PMID- 22961804
TI  - Neuronal plasticity in chronic pancreatitis is mediated via the
      neurturin/GFRalpha2 axis.
AB  - The glial cell line-derived neurotrophic factor (GDNF) family member neurturin
      (NRTN) and its receptor GFRalpha2 play a deciding role in the normal development
      of pancreatic parasympathetic innervation. In this study, we aimed at
      investigating the role of NRTN/GFRalpha2 axis in pancreatic neuropathy in human
      chronic pancreatitis (CP). Expression of NRTN/GFRalpha2 was compared between
      normal human pancreas (NP) and CP tissues via immunohistochemistry,
      immunoblotting, and quantitative RT-PCR and correlated to abdominal pain
      sensation. To elucidate the impact of NRTN in pancreatic neuroplasticity,
      neuronal phenotype and glial density were quantified via an in vitro
      neuroplasticity assay in dissociated newborn rat dorsal root ganglia (DRG)
      cultured 1) in CP tissue extracts depleted from NRTN, 2) in NP, 3) in untreated
      CP tissue extracts, and 4) CP extracts in which nerve growth factor, glial cell
      derived-neurotrophic factor, or TGF-beta(1) was depleted. NRTN and GFRalpha2 were
      highly upregulated in CP, especially in intrapancreatic nerves and the
      extracellular matrix. CP tissue demonstrated increased amounts of mature
      multimeric NRTN and elevated levels of GFRalpha2. The noticeable neurotrophic
      effect of CP tissue extracts on DRG neurons was diminished upon blockade of NRTN
      from these extracts. However, blockade of NRTN from CP extracts did not influence
      the density of DRG glia cells. In conclusion, the NRTN/GFRalpha2 axis is
      activated during the course of CP and represents a major key player in the
      reactive neural alterations in CP. This is the first study to provide functional
      evidence for the contribution of neurotrophic factors to neuroplasticity in CP.

PMID- 22961806
TI  - An efficient thiol-ene chemistry for the preparation of amphiphilic PHA-based
      graft copolymers.
AB  - We present a straightforward method to prepare amphiphilic graft copolymers
      consisting of hydrophobic poly(3-hydroxyalkanoates) (PHAs) backbone and
      hydrophilic alpha-amino-omega-methoxy poly(oxyethylene-co-oxypropylene)
      (Jeffamine(r)) units. Poly(3-hydroxyoctanoate)-co-(3-hydroxyundecenoate) (PHOU)
      was first methanolyzed to obtain the desired molar mass. The amino end groups of
      Jeffamine were converted into thiol by a reaction with N-acetylhomocysteine
      thiolactone and subsequently photografted. This "one-pot" functionalization
      prevents from arduous and time-consuming functionalization of the hydrophilic
      precursor or tedious modifications of PHAs, thus simplifying the process. The
      amphiphilic nature of modified PHAs leads to water-soluble copolymers exhibiting
      thermoresponsive behavior.

PMID- 22961805
TI  - Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during
      and following recovery from chemical colitis.
AB  - Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide
      ongoing inhibitory tone to the gastrointestinal tract and receive innervation
      from mechanosensory intestinofugal afferent neurons primarily located in the
      colon and rectum. This study tests the hypothesis that colitis alters the
      excitability of PVG neurons. Intracellular recording techniques were used to
      evaluate changes in the electrical properties of inferior mesenteric ganglion
      (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models
      of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h,
      but not 6 h, post-TNBS during "acute" inflammation. Hyperexcitability persisted
      at 6 days post-TNBS during "chronic" inflammation, as well as at 56 days post
      TNBS when colitis had resolved. In contrast, there was only a modest decrease in
      the current required to elicit an action potential at 24 h after acetic acid
      administration. Vasomotor neurons from inflamed preparations exhibited normal
      excitability. The excitatory effects of XE-991, a blocker of the channel that
      contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of
      the channel that contributes to the A-type potassium current, were unchanged in
      TNBS-inflamed preparations, suggesting that these currents did not contribute to
      hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused
      tonic visceromotor neurons to accommodate to sustained current pulses, regardless
      of the inflammatory state of the preparation, and restored a normal rheobase in
      neurons from TNBS-inflamed preparations but did not alter the rheobase of control
      preparations, suggesting that enhanced activity of voltage-gated sodium channels
      may contribute to colitis-induced hyperexcitability. Collectively, these data
      indicate that enhanced sympathetic drive as a result of hyperexcitable
      visceromotor neurons may contribute to small bowel dysfunction during colitis.

PMID- 22961807
TI  - Application of copulas to improve covariance estimation for partial least
      squares.
AB  - Dimension reduction techniques, such as partial least squares, are useful for
      computing summary measures and examining relationships in complex settings.
      Partial least squares requires an estimate of the covariance matrix as a first
      step in the analysis, making this estimate critical to the results. In addition,
      the covariance matrix also forms the basis for other techniques in multivariate
      analysis, such as principal component analysis and independent component
      analysis. This paper has been motivated by an example from an imaging study in
      Alzheimer's disease where there is complete separation between Alzheimer's and
      control subjects for one of the imaging modalities. This separation occurs in one
      block of variables and does not occur with the second block of variables
      resulting in inaccurate estimates of the covariance. We propose the use of a
      copula to obtain estimates of the covariance in this setting, where one set of
      variables comes from a mixture distribution. Simulation studies show that the
      proposed estimator is an improvement over the standard estimators of covariance.
      We illustrate the methods from the motivating example from a study in the area of
      Alzheimer's disease.

PMID- 22961809
TI  - Platycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS
      human gastric cancer cells.
AB  - Mitogen-activated protein kinases (MAPKs) cascades play important roles in cell
      proliferation, death, and differentiation in response to external stimuli.
      However, the precise role of MAPKs in platycodin D (PD)-induced cytotoxicity
      remains unclear. In this study, we investigated the anticancer effect of PD and
      its underlying mechanism on AGS human gastric cancer cells. PD significantly
      inhibited cell proliferation and induced anoikis, which is a form of apoptosis in
      which cells detach from the substrate. It showed phosphatidylserine
      externalization, DNA fragmentation, increase of sub-G1 phase, and activation of
      caspases in a dose- and time-dependent manner. This apoptosis has been associated
      with the extrinsic pathway via Fas-L and the intrinsic pathway via mitochondrial
      Bcl-2 family members. Moreover, PD led to the phosphorylation of stresses
      activated protein kinases such as JNK and p38, followed by the activation of AP
      1. However, pretreatment with SB203580 (a p38 specific inhibitor) suppressed PD
      induced p38 and AP-1 activation, and subsequently attenuated the PD-induced
      apoptosis in AGS cells. These results suggest that p38 activation is responsible
      for PD-induced apoptosis in AGS cells and PD might be useful for the development
      as the anticancer agent of gastric cancer.

PMID- 22961808
TI  - ALKBH1 is a histone H2A dioxygenase involved in neural differentiation.
AB  - AlkB homolog 1 (ALKBH1) is one of nine members of the family of mammalian AlkB
      homologs. Most Alkbh1(-/-) mice die during embryonic development, and survivors
      are characterized by defects in tissues originating from the ectodermal lineage.
      In this study, we show that deletion of Alkbh1 prolonged the expression of
      pluripotency markers in embryonic stem cells and delayed the induction of genes
      involved in early differentiation. In vitro differentiation to neural progenitor
      cells (NPCs) displayed an increased rate of apoptosis in the Alkbh1(-/-) NPCs
      when compared with wild-type cells. Whole-genome expression analysis and
      chromatin immunoprecipitation revealed that ALKBH1 regulates both directly and
      indirectly, a subset of genes required for neural development. Furthermore, our
      in vitro enzyme activity assays demonstrate that ALKBH1 is a histone dioxygenase
      that acts specifically on histone H2A. Mass spectrometric analysis demonstrated
      that histone H2A from Alkbh1(-/-) mice are improperly methylated. Our results
      suggest that ALKBH1 is involved in neural development by modifying the
      methylation status of histone H2A.

PMID- 22961810
TI  - NMR spectroscopic analysis reveals extensive binding interactions of complex
      xyloglucan oligosaccharides with the Cellvibrio japonicus glycoside hydrolase
      family 31 alpha-xylosidase.
AB  - The study of the interaction of glycoside hydrolases with their substrates is
      fundamental to diverse applications in medicine, food and feed production, and
      biomass-resource utilization. Recent molecular modeling of the alpha-xylosidase
      CjXyl31A from the soil saprophyte Cellvibrio japonicus, together with protein
      crystallography and enzyme-kinetic analysis, has suggested that an appended PA14
      protein domain, unique among glycoside hydrolase family 31 members, may confer
      specificity for large oligosaccharide fragments of the ubiquitous plant
      polysaccharide xyloglucan (J. Larsbrink, A. Izumi, F.M. Ibatullin, A. Nakhai,
      H.J. Gilbert, G.J. Davies, H. Brumer, Biochem. J. 2011, 436, 567-580). In the
      present study, a combination of NMR spectroscopic techniques, including
      saturation transfer difference (STD) and transfer NOE (TR-NOE) spectroscopy, was
      used to reveal extensive interactions between CjXyl31A active-site variants and
      xyloglucan hexa- and heptasaccharides. The data specifically indicate that the
      enzyme recognizes the entire cello-tetraosyl backbone of the substrate and
      product in positive enzyme subsites and makes further significant interactions
      with internal pendant alpha-(1->6)-linked xylosyl units. As such, the present
      analysis provides an important rationalization of previous kinetic data on
      CjXyl31A and unique insight into the role of the PA14 domain, which was not
      otherwise obtainable by protein crystallography.

PMID- 22961811
TI  - Determination of thiols by capillary micellar electrokinetic chromatography with
      laser induced fluorescence detection using 1,3,5,7-tetramethyl-8-phenyl-(4
      iodoacetamido) difluoroboradiaza-s-indacene as labeling reagent.
AB  - A sensitive and effective micellar electrokinetic capillary chromatography with
      laser-induced fluorescence detection approach was described for the determination
      of low molecular-mass thiols using 1,3,5,7-tetramethyl-8-phenyl-(4-iodoacetamido)
      difluoroboradiaza-s-indacene as the labeling reagent. After precolumn
      derivatization, baseline separation of six thiol compounds including cysteine,
      glutathione, N-acetylcysteine, homocysteine, 6-mercaptopurine, and penicillamine
      were achieved within 18 min. The optimal running buffer was composed of mixtures
      involving 25 mM sodium dodecyl sulfate, 25% (v/v) acetonitrile and 15 mM sodium
      phosphate buffer, pH 7.5. The detection limits (S/N = 3) were found as low as 40
      pM under argon ion laser-induced fluorescence detector (lambda(ex)/lambda(em) =
      488/520 nm), which were much better than the reported approaches. The accuracy
      and specificity of this assay for real samples were assured by a standard
      addition method. The proposed method has been applied to the analysis of thiols
      both in human plasma and plum flower samples with recoveries of 92.0-109.4%.

PMID- 22961812
TI  - Expression of a functional recombinant C-type lectin-like protein lebecetin in
      the human embryonic kidney cells.
AB  - Lebecetin is an anticoagulant C-type lectin-like protein that was previously
      isolated from Macrovipera lebetina venom and described to consist of two subunits
      (alpha and beta). It was reported to potently prevent platelet aggregation by
      binding to glycoprotein Ib and to exhibit a broad spectrum of inhibitory
      activities on various integrin-mediated functions of tumor cells, including
      adhesion, proliferation, and cell migration. This study aimed to investigate the
      structure-function of lebecetin. Accordingly, the cDNA of each subunit was cloned
      and separately or jointly expressed in the human embryonic kidney cells using two
      vectors with different selectable tags. The immunofluorescence analysis of
      transfected cells revealed significant expression levels and co-localization of
      the two lebecetin subunits. The recombinant proteins were efficiently secreted
      and purified using metal-chelating affinity chromatography. We found that the
      Lebecetin alpha and beta subunits were produced as a mixture of homodimers and
      heterodimers and that the heterodimerization represents a prerequisite for
      functioning.

PMID- 22961813
TI  - Evaluation of incremental healthcare resource burden and readmission rates
      associated with hospitalized hyponatremic patients in the US.
AB  - BACKGROUND: Hyponatremia is a prevalent electrolyte disorder in hospitalized
      patients indicative of greater morbidity and mortality. A large-scale
      retrospective analysis was conducted to evaluate the incremental burden of
      hospitalized hyponatremic (HN) versus non-HN patients in terms of hospital
      resource utilization, costs, and hospital readmissions in the real-world setting.
      METHODS: HN patients (>=18 years) were selected from the Premier Hospital
      Database between January 1, 2007 and March 31, 2010 and matched to a non-HN
      control cohort using propensity score matching. Bivariate and multivariate
      statistics were employed to evaluate the differences in healthcare resource
      utilization, costs, and hospital readmissions between patient cohorts. RESULTS:
      Among the matched patient cohorts, length of stay (LOS) (8.8 +/- 10.3 vs 7.7 +/-
      8.5 days, P < 0.001), hospital admission costs ($15,281 +/- $24,054 vs $13,439 +/
      $22,198, P < 0.001), intensive care unit (ICU) LOS (5.5 +/- 7.9 vs 4.9 +/- 7.1
      days, P < 0.001), and ICU costs ($8525 +/- $13,342 vs $7597 +/- $12,695, P <
      0.001) were greater for the HN versus non-HN cohort, as were hospital readmission
      rates 30 days postdischarge. Multivariate regressions further demonstrated that
      hyponatremia was associated with an increase of 10.9% for LOS, 8.2% for total
      hospitalization costs, 10.2% for ICU LOS, and 8.9% for ICU costs. Additionally,
      after multivariate adjustment, hyponatremia was associated with a 15.0% increased
      chance for hospital readmission 30 days postdischarge (P < 0.0001). CONCLUSIONS:
      Hyponatremia is an independent predictor of increased hospitalization LOS and
      cost, ICU admission and cost, and 30-day hospital readmission, and therefore
      represents a potential target for intervention to reduce healthcare expenditures
      for a large population of hospitalized hyponatremic patients.

PMID- 22961815
TI  - Demonstration of type II latency in T lymphocytes of Epstein-Barr Virus
      associated hemophagocytic lymphohistiocytosis.
AB  - Epstein-Barr virus (EBV) is the most common infectious cause of non-genetic
      hemophagocytic lymphohistiocytosis (HLH). To investigate EBV-infected lymphocytes
      and immune dysfunction in EBV-associated HLH, blood samples from a 6-year-old boy
      were longitudinally analyzed using molecular techniques. EBV-positive lymphocytes
      were detected as CD5(+) , CD8(+) , and/or HLA DR(+) lymphocytes on Day 25 of the
      disease, mostly disappearing thereafter. CD8(+) cells specific for lytic antigen
      BRLF1 were detected, but cells specific for latent antigens EBNA3 and LMP2 were
      not. EBV genes EBNA1, LMP1, LMP2, EBER1, BARTs were detected, suggesting a
      latency type II gene expression pattern in this case.

PMID- 22961814
TI  - 5-HT(1B)  autoreceptor regulation of serotonin transporter activity in
      synaptosomes.
AB  - Serotonin-1B (5-HT(1B) ) autoreceptors are located in serotonin (5-HT) terminals,
      along with serotonin transporters (SERT), and play a critical role in
      autoregulation of serotonergic neurotransmission and are implicated in disorders
      of serotonergic function, particularly emotional regulation. SERT modulates
      serotonergic neurotransmission by high-affinity reuptake of 5-HT. Alterations in
      SERT activity are associated with increased risk for depression and anxiety.
      Several neurotransmitter receptors are known to regulate SERT K(m) and V(max) ,
      and previous work suggests that 5-HT(1B) autoreceptors may regulate 5-HT
      reuptake, in addition to modulating 5-HT release and synthesis. We used rotating
      disk electrode voltammetry to investigate 5-HT(1B) autoreceptor regulation of
      SERT-mediated 5-HT uptake into synaptosomes. The selective 5-HT(1B) antagonist
      SB224289 decreased SERT activity in synaptosomes prepared from wild-type but not
      5-HT(1B) knockout mice, whereas SERT uptake was enhanced after pretreatment with
      the selective 5-HT(1B) agonist CP94253. Furthermore, SERT activity varies as a
      function of 5-HT(1B) receptor expression-specifically, genetic deletion of 5
      HT(1B) decreased SERT function, while viral-mediated overexpression of 5-HT(1B)
      autoreceptors in rat raphe neurons increased SERT activity in rat hippocampal
      synaptosomes. Considered collectively, these results provide evidence that 5
      HT(1B) autoreceptors regulate SERT activity. Because SERT clearance rate varies
      as a function of 5-HT(1B) autoreceptor expression levels and is modulated by both
      activation and inhibition of 5-HT(1B) autoreceptors, this dynamic interaction may
      be an important mechanism of serotonin autoregulation with therapeutic
      implications.

PMID- 22961816
TI  - Polymorphisms upstream of the melanocortin-1 receptor coding region are
      associated with human pigmentation variation in a Brazilian population.
AB  - OBJECTIVE: We describe an association of two SNPs, rs3212345:C>T and
      rs3212346:G>A, located approximately 2.5 kb upstream of the melanocortin-1
      receptor (MC1R) translation initiation codon, with pigmentation phenotype
      variation in a Southeast Brazilian miscegenated population. METHODS: One hundred
      thirty-eight genetically unrelated subjects, with multicolor phenotype, were
      selected from the southeast region of Brazil. Skin, hair and eye color, and
      tanning ability were rated. Genotypes for each SNP (rs3212345:C>T and
      rs3212346:G>A) were determined. A logistic regression analysis was performed with
      the additive model to determine which of the polymorphisms contributed to a
      specific phenotype. RESULTS: We found that the rs3212345:C>T is associated with
      light skin, red hair, and poor tanning ability, while the rs3212346:G>A is
      associated with dark skin, black hair, and strong tanning ability. The presence
      of rs3212345-C and rs3212346-A alleles in human, chimpanzee, gorilla, orangutan,
      and marmoset genomes suggests that they are the ancestral alleles. CONCLUSION:
      These data suggest that the rs3212345-T and rs3212346-G alleles may have
      contributed to lighter pigmentation phenotypes in modern humans. Genotyping for
      these SNPs may prove useful to the fields of molecular anthropology and forensic
      genetics.

PMID- 22961817
TI  - Magnesium nanocrystals embedded in a metal-organic framework: hybrid hydrogen
      storage with synergistic effect on physi- and chemisorption.
AB  - Hexagonal-disk-shaped magnesium nanocrystals (MgNCs) are fabricated within a
      porous metal-organic framework (MOF, see picture). The MgNCs@MOF stores hydrogen
      by both physi- and chemisorptions, exhibiting synergistic effects to decrease the
      isosteric heat of H(2) physisorption compared with that of pristine MOF, and
      decrease the H(2) chemisorption/desorption temperatures by 200 K compared with
      those of bare Mg powder.

PMID- 22961818
TI  - A needle in a haystack: Identifying biomarkers to personalize systemic therapy in
      patients with hepatocellular carcinoma.

PMID- 22961819
TI  - An efficient algorithm for complete active space valence bond self-consistent
      field calculation.
AB  - This article describes a novel algorithm for the optimization of valence bond
      self-consistent field (VBSCF) wave function for a complete active space (CAS), so
      called VBSCF(CAS). This was achieved by applying the strategies adopted in the
      optimization of CASSCF wave functions to VBSCF(CAS) wave functions, using an
      auxiliary orthogonal orbital set that generates the same configuration space as
      the original nonorthogonal orbital set. Theoretical analyses and test
      calculations show that the VBSCF(CAS) method shares the same computational
      scaling as CASSCF. The test calculations show the current capability of VBSCF
      method, which involves millions of VB structures.

PMID- 22961820
TI  - Characterization of Bombyx mori nucleopolyhedrovirus Bm17.
AB  - Open reading frame17 (Bm17) of Bombyx mori nucleopolyhedrovirus is a highly
      conserved gene in lepidopteran nucleopolyhedroviruses, suggesting that it
      performs an important role in the virus life cycle whose function is unknown. In
      this report, we describe the characterization of Bm17. Reversed transcriptive-PCR
      (RT-PCR) and Western blot analysis demonstrated that Bm17 was expressed as a late
      gen. Immunofluorescence analysis by confocal microscopy showed that BM17 protein
      was localized on cytoplasm and nucleus of infected cells. These results show that
      BM17 was a late protein localized in cytoplasm and nucleus. 

PMID- 22961821
TI  - To screen or not to screen patients with an idiopathic venous thrombosis for an
      occult cancer: Netherlands versus the world: 1-0?

PMID- 22961822
TI  - Comorbidity complicates cardiovascular treatment: is diabetes the exception?
AB  - BACKGROUND: Many patients with cardiovascular disease do not attain the targets
      for health-related lifestyle and preventive treatment recommended in practice
      guidelines. The aim of this study was to assess the impact of diabetes (DM) and
      chronic obstructive pulmonary disease (COPD) on the quality of cardiovascular
      risk management in patients with established cardiovascular diseases (CVD).
      METHODS AND RESULTS: Patients with established CVD were randomly selected in
      primary care practices using recorded diagnoses. Structured case forms were used
      to review data on 20 performance indicators concerning CVD from medical records.
      Descriptive and multilevel regression analyses were conducted. In 45 primary care
      practices with 106 physicians in the Netherlands, 1614 medical records of
      patients with CVD (37.9% women) were reviewed. A total of 1076 (66.7%) patients
      had recorded CVD only (reference group); 7.8% had CVD and COPD; 22.4% had CVD and
      DM; 3.1% patients had CVD, COPD and DM. Compared with the reference group,
      patients with CVD and DM yielded higher scores on 17 of 20 indicators; patients
      with CVD, DM and COPD on 14 indicators; and patients with CVD and COPD on three
      indicators. Of the patients with CVD and DM, fewer patients had LDL-cholesterol
      levels over 2.5 mmol/l (OR=0.36; 95% CI 0.26-0.50), more had antiplatelet drugs
      prescribed (OR=1.72; 95% CI 1.17-2.54), and more had systolic blood pressure
      measurement (OR=4.12; 95% CI 2.80-6.06). CONCLUSIONS: This study showed that DM
      but not COPD was associated with more comprehensive cardiovascular risk
      management. This finding adds to cumulating evidence that presence of DM is
      associated with better preventive treatment of cardiovascular risk.

PMID- 22961823
TI  - Effect of the factor V Leiden mutation on the incidence and outcome of severe
      infection and sepsis.
AB  - Activation of coagulation frequently occurs in severe infection and sepsis and
      may contribute to the development of multiple organ dysfunction. Factor V Leiden
      is a relatively common mutation resulting in a mild prohaemostatic state and
      consequently with an increased tendency to develop thrombosis. Hypothetically,
      patients with factor V Leiden may suffer from more severe coagulopathy in case of
      severe infection or sepsis. Aggravation of the procoagulant state in sepsis may
      subsequently result in more severe organ dysfunction and an increased risk of
      death. Here we discuss the experimental and clinical evidence regarding the
      relationship between the presence of a factor V Leiden mutation and the incidence
      and outcome of sepsis.

PMID- 22961824
TI  - Limitations of screening for occult cancer in patients with idiopathic venous
      thromboembolism.
AB  - BACKGROUND: Idiopathic venous thrombosis (IVT) is associated with occult
      malignancy in 10% of patients. The Trousseau study investigated whether extensive
      screening using abdominal and chest computed tomography (CT) scans and
      mammography in women would decrease mortality, compared with limited screening.
      Here, the costs and test characteristics of these screening strategies are
      presented, including true- and false-positive findings, sensitivity and
      specificity. METHODS: All investigations performed because of a suspicion of
      malignancy in the limited or extensive screening groups were collected. Costs
      were calculated using Dutch healthcare tariffs. RESULTS: A total of 342 and 288
      patients with IVT were included in the extensive and the limited screening group,
      respectively. The prevalences of malignancy and mortality were comparable between
      these two groups, as were the abnormal findings during routine screening. In 30%
      of the extensively screened patients, the CT scans or mammography showed
      abnormalities necessitating further diagnostic work-up; this yielded six
      malignancies and resulted in a positive predictive value of 6.6%, sensitivity of
      33% and specificity of 70%. Mean costs per patient were ?165.17 for the routine
      and ?530.92 for the extensive screening. CONCLUSION: Screening using CT scans and
      mammography results in extra costs due to the high percentage of false-positive
      findings for which a further diagnostic work-up is indicated.

PMID- 22961825
TI  - Hypogonadism in a patient with mild hereditary haemochromatosis.
AB  - Hypogonadism is a potential complication of haemochromatosis, usually seen in
      patients with severe iron overload and liver cirrhosis. We describe the
      diagnostic workup of a patient with an early stage of hereditary
      haemochromatosis, presenting with only mildly elevated liver enzymes and central
      hypogonadism in the absence of cirrhosis or diabetes, but with concurrent
      sarcoidosis.

PMID- 22961826
TI  - A 'chigsaw' puzzle after a vacation in Brazil.

PMID- 22961827
TI  - A strange looking face in the stomach.

PMID- 22961828
TI  - A young man with odynophagia, nausea and vomiting.

PMID- 22961829
TI  - An odd looking man.

PMID- 22961830
TI  - Therapeutic drug monitoring of free fraction valproic acid in patients with
      hypoalbuminaemia.

PMID- 22961831
TI  - A dialysis patient with a life-threatening hyperkalaemia due to the use of a low
      salt spread.

PMID- 22961832
TI  - How much effect of different antihypertensive medications on cardiovascular
      outcomes is attributable to their effects on blood pressure?
AB  - The debate over whether certain antihypertensive medications have benefits beyond
      what would be expected from their blood pressure lowering spurred the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial,
      which randomized 42,418 participants to chlorthalidone (15,255), amlodipine
      (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the
      active control, with each of the other three agents with respect to the primary
      outcome, fatal coronary heart disease or nonfatal myocardial infarction, and
      several other clinical endpoints. The arms were similar with respect to the
      primary endpoint, although some differences were found for other endpoints, most
      notably heart failure. Although the desire was to achieve similar blood pressure
      reductions in the four arms, we found some systolic blood pressure and diastolic
      blood pressure differences. A natural question is to what degree can observed
      treatment group differences in cardiovascular outcomes be attributed to these
      blood pressure differences. The purpose of this paper was to delineate the
      problems inherent in attempting to answer this question, and to present analyses
      intended to overcome these problems.

PMID- 22961833
TI  - Analysis of amino acids in latent fingerprint residue by capillary
      electrophoresis-mass spectrometry.
AB  - The analysis of the chemical composition of fingerprints is important for the
      development and improvement of existing fingerprint enhancement techniques. This
      study demonstrates the first analysis of a latent fingerprint sample, using an
      optimized CE-MS method. In total 12 amino acids were detected in the fingerprint
      sample. MS/MS fragmentation was used to provide additional identity confirmation,
      for which eight of the twelve detected amino acids generated confirmatory product
      ions. Nine amino acids were quantified and their relative abundances were
      consistent with previous studies with serine and glycine being the most abundant.
      The successful detection of amino acids from latent fingerprints demonstrates
      that CE-MS is a potential future technique for further study of such compounds in
      fingerprint samples.

PMID- 22961834
TI  - Neuroanatomy of titanosaurid dinosaurs from the upper cretaceous of Patagonia,
      with comments on endocranial variability within sauropoda.
AB  - The purpose of this study is to provide a detailed description of the
      neuroanatomy of Bonatitan, Antarctosaurus, and an unnamed titanosaur from Rio
      Negro, Argentina including the first observations on the inner ear of the two
      first taxa using CT scans. The materials were compared with previously described
      sauropod endocasts and other less complete titanosaur braincases from Argentina.
      The cranial endocasts show the general morphology of other sauropods being
      bulbous, anteroposteriorly short and transversely wide, and with enlarged and
      posteroventrally projected pituitary body. Particular titanosaur traits are the
      extremely short and horizontal olfactory tract, the absence of a floccular
      process and a single root for cranial nerve XII. In addition, in the basicranium
      the abducens nerve (CN VI) does not penetrates the pituitary fossa and the
      internal carotid artery enters the medial aspect of the basipterygoid process,
      resulting in an external opening for this vessel that is not visible in lateral
      view of the braincase. The titanosaurid inner ear also exhibits particular
      traits, such as robust semicircular canals, and anterior and posterior
      semicircular canals that are subequal in size. The variation observed in the
      sauropod endocranium indicates an evolutionary tendency in titanosaurs toward the
      anteroposterior shortening of the midbrain, and the reduction in size of the
      semicircular canals of the inner ear, in particular the anterior semicircular
      canal. This, together with the lack of floccular process suggests a narrower
      range of movements of the head for this clade.

PMID- 22961835
TI  - Effects of mechanical stimulation induced by compression and medium perfusion on
      cardiac tissue engineering.
AB  - Cardiac tissue engineering presents a challenge due to the complexity of the
      muscle tissue and the need for multiple signals to induce tissue regeneration in
      vitro. We investigated the effects of compression (1 Hz, 15% strain) combined
      with fluid shear stress (10(-2) -10(-1) dynes/cm(2) ) provided by medium
      perfusion on the outcome of cardiac tissue engineering. Neonatal rat cardiac
      cells were seeded in Arginine-Glycine-Aspartate (RGD)-attached alginate
      scaffolds, and the constructs were cultivated in a compression bioreactor. A
      daily, short-term (30 min) compression (i.e., "intermittent compression") for 4
      days induced the formation of cardiac tissue with typical striation, while in the
      continuously compressed constructs (i.e., "continuous compression"), the cells
      remained spherical. By Western blot, on day 4 the expression of the gap junction
      protein connexin 43 was significantly greater in the "intermittent compression"
      constructs and the cardiomyocyte markers (alpha-actinin and N-cadherin) showed a
      trend of better preservation compared to the noncompressed constructs. This
      regime of compression had no effect on the proliferation of nonmyocyte cells,
      which maintained low expression level of proliferating cell nuclear antigen.
      Elevated secretion levels of basic fibroblast growth factor and transforming
      growth factor-beta in the daily, intermittently compressed constructs likely
      attributed to tissue formation. Our study thus establishes the formation of an
      improved cardiac tissue in vitro, when induced by combined mechanical signals of
      compression and fluid shear stress provided by perfusion.

PMID- 22961836
TI  - Tailored star block copolymer architecture for high performance chemically
      amplified resists.
AB  - Star block copolymers are demonstrated for their application as a high
      performance resist material. This new resist material shows advanced progress in
      sensitivity and solubility contrast and is finally combinatorially optimized to
      achieve a 66 nm line/space pattern. The tailored molecular architecture of the
      star block copolymer is synthesized via core-first atom transfer radical
      polymerization (ATRP) and shows narrow polydispersity indices below 1.2.

PMID- 22961837
TI  - Retinoic acid and the transcription factor MafB act together and differentially
      to regulate aggrecan and matrix metalloproteinase gene expression in neonatal
      chondrocytes.
AB  - Vitamin A (VA) and its active form, retinoic acid (RA), are regulators of
      skeletal development and chondrogenesis. MafB, a transcription factor, has been
      identified as an important mediator in monocyte and osteoclast differentiation.
      However, the presence and function of MafB in chondrocytes is not clear. In this
      study, MafB gene expression was regulated by both the VA status of the mother (VA
      marginal, adequate, and supplemented diets) and by direct oral supplementation of
      the neonates with VARA (VA mixed with 10% RA). Expression was highest in neonates
      of VA-supplemented versus VA-marginal dams (P < 0.05), and in VARA-treated versus
      placebo-treated neonates across all diet groups (P < 0.05). To examine cellular
      changes, primary chondrocytes derived from neonatal rat ribs were cultured in the
      presence of RA for up to 48 h. MafB mRNA exhibited a time- and dose-dependent
      increase in response to RA, while the induction of MafB mRNA was attenuated by
      BMS-493, a pan-RAR inverse agonist, implicating RAR signaling in the regulation
      of MafB. The genetic knockdown of MafB in chondrocytes using siRNA (MafB(SI)
      chondrocytes) abrogated the RA-induced increase in MafB expression. MafB(SI)
      chondrocytes expressed higher levels of aggrecan mRNA. Additionally, the
      increased matrix metalloproteinase (MMP)3 and MMP13 gene expression due to RA was
      attenuated in MafB(SI) chondrocytes, while total extracellular matrix staining
      was increased. These results support a role for MafB as a regulator of
      chondrocyte gene expression and matrix formation via control of aggrecan, MMP3
      and MMP13 expression, and indicate an important role for RA in the regulation of
      MafB.

PMID- 22961838
TI  - Carers' assessment, skills and information sharing: theoretical framework and
      trial protocol for a randomised controlled trial evaluating the efficacy of a
      complex intervention for carers of inpatients with anorexia nervosa.
AB  - Experienced Carers Helping Others (ECHO) is a guided self-help intervention for
      carers of people with eating disorders to reduce distress and ameliorate
      interpersonal maintaining factors to improve patient outcomes. The aim of this
      paper is to describe the theoretical background and protocol of a randomised
      controlled trial that will establish whether ECHO has a significant beneficial
      effect for carers and the person they care for. Individuals with anorexia nervosa
      and carers will be recruited from eating disorder inpatient/day patient hospital
      services in the UK. Primary outcomes are time until relapse post-discharge
      (patient) and distress (carer) at 12 months post-discharge. Secondary outcomes
      are body mass index, eating disorder symptoms, psychosocial measures and health
      economic data for patients and carers. Carers will be randomised (stratified by
      site and illness severity) to receive ECHO (in addition to treatment as usual) or
      treatment as usual only. Potential difficulties in participant recruitment and
      delivery of the intervention are discussed.

PMID- 22961840
TI  - Community-based outreach may reduce distress in women exposed to intimate partner
      abuse more than system-based referral.

PMID- 22961841
TI  - Hyperactivity/impulsivity in childhood, but not inattention, is associated with
      early-onset tobacco and alcohol use.

PMID- 22961839
TI  - Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon
      cancer risk.
AB  - SCOPE: The importance of folate-mediated one-carbon metabolism (FOCM) in
      colorectal carcinogenesis is emphasized by observations that high dietary folate
      intake is associated with decreased risk of colon cancer (CC) and its precursors.
      Additionally, polymorphisms in FOCM-related genes have been repeatedly associated
      with risk, supporting a causal relationship between folate and colorectal
      carcinogenesis. METHODS AND RESULTS: We investigated ten candidate polymorphisms
      with defined or probable functional impact in eight FOCM-related genes (SHMT1,
      DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, and TDG) in 1609 CC cases and 1974
      controls for association with CC risk and for interaction with dietary factors.
      No polymorphism was statistically significantly associated with overall risk of
      CC. However, statistically significant interactions modifying CC risk were
      observed for DNMT1 I311V with dietary folate, methionine, vitamin B2 , and
      vitamin B12 intake and for MTRR I22M with dietary folate, a predefined one-carbon
      dietary pattern, and vitamin B6 intake. We observed statistically significant
      gene-diet interactions with five additional polymorphisms. CONCLUSION: Our
      results provide evidence that FOCM-related dietary intakes modify the association
      between CC risk and FOCM allelic variants. These findings add to observations
      showing that folate-related gene-nutrient interactions play an important role in
      modifying the risk of CC.

PMID- 22961842
TI  - Artificial signal transduction with primary and secondary messengers.
AB  - The complete, entirely artificial, signal-transduction process was realized with
      a pair of tailored transmembrane units that were equipped with receptor- and
      reactive sites at both amphiphilic ends. Thus, docking of the primary messenger,
      transmission of the signal, and release of the secondary messenger could all be
      imitated in a single experimental setup. The system imitates the signaling
      principle of receptor tyrosine kinases and employs bisphosphonate head-groups for
      oligoamine-recognition and a pair of thiol nucleophiles and pyridine disulfide
      tail-groups for intravesicle S(N)2 displacement. This system operates in a
      unidirectional fashion, does not suffer from intervesicle competition, and is
      highly sensitive towards the lipid composition of the membrane and the nature of
      the primary messenger.

PMID- 22961843
TI  - The osteogenic differentiation improvement of human mesenchymal stem cells on
      titanium grafted with polyNaSS bioactive polymer.
AB  - Osseointegration of metallic implants used in orthopedic surgery requires that
      osteoprogenitor cells attach and adhere to the surface, then proliferate,
      differentiate into osteoblasts, and finally produce mineralized matrix. Because
      the ability of progenitor cells to attach to a scaffold surface during early
      stages is important in the development of new tissue structures, we developed in
      our laboratory, a strategy involving grafting of implants with a polymer of
      sodium styrene sulfonate (polyNaSS) used as a scaffold which enables human
      mesenchymal stem cells (hMSCs) interactions. In the present study, we
      investigated the cellular response of hMSCs to polyNaSS surfaces of titanium
      (Ti). In particular, cell proliferation, cell viability, cell differentiation,
      and cell spreading were evaluated. Results showed that cell proliferation and
      cell viability did not differ with any statistical significance between modified
      and unmodified Ti surfaces. Interestingly, culture of MSCs on polyNaSS surfaces
      resulted in a significant increase of cell spreading and cell differentiation
      compared with the other tested surfaces. These results suggest that titanium
      surface grafted with polyNaSS is a suitable scaffold for bone tissue engineering.

PMID- 22961844
TI  - Coronary obstruction following TAVI valve-in-valve: could we prevent it?

PMID- 22961845
TI  - Transition metal complexes of anionic N-heterocyclic dicarbene ligands.

PMID- 22961846
TI  - Alternative excision repair of ultraviolet B- and C-induced DNA damage in dormant
      and developing spores of Bacillus subtilis.
AB  - The nucleotide excision repair (NER) and spore photoproduct lyase DNA repair
      pathways are major determinants of Bacillus subtilis spore resistance to UV
      radiation. We report here that a putative ultraviolet (UV) damage endonuclease
      encoded by ywjD confers protection to developing and dormant spores of B.
      subtilis against UV DNA damage. In agreement with its predicted function, a
      His(6)-YwjD recombinant protein catalyzed the specific incision of UV-irradiated
      DNA in vitro. The maximum expression of a reporter gene fusion to the ywjD
      opening reading frame occurred late in sporulation, and this maximal expression
      was dependent on the forespore-specific RNA polymerase sigma factor, sigma(G).
      Although the absence of YwjD and/or UvrA, an essential protein of the NER
      pathway, sensitized developing spores to UV-C, this effect was lower when these
      cells were treated with UV-B. In contrast, UV-B but not UV-C radiation
      dramatically decreased the survival of dormant spores deficient in both YwjD and
      UvrA. The distinct range of lesions generated by UV-C and UV-B and the different
      DNA photochemistry in developing and dormant spores may cause these differences.
      We postulate that in addition to the UvrABC repair system, developing and dormant
      spores of B. subtilis also rely on an alternative excision repair pathway
      involving YwjD to deal with the deleterious effects of various UV photoproducts.

PMID- 22961847
TI  - Insights into glycogen metabolism in chemolithoautotrophic bacteria from
      distinctive kinetic and regulatory properties of ADP-glucose pyrophosphorylase
      from Nitrosomonas europaea.
AB  - Nitrosomonas europaea is a chemolithoautotroph that obtains energy by oxidizing
      ammonia in the presence of oxygen and fixes CO(2) via the Benson-Calvin cycle.
      Despite its environmental and evolutionary importance, very little is known about
      the regulation and metabolism of glycogen, a source of carbon and energy storage.
      Here, we cloned and heterologously expressed the genes coding for two major
      putative enzymes of the glycogen synthetic pathway in N. europaea, ADP-glucose
      pyrophosphorylase and glycogen synthase. In other bacteria, ADP-glucose
      pyrophosphorylase catalyzes the regulatory step of the synthetic pathway and
      glycogen synthase elongates the polymer. In starch synthesis in plants,
      homologous enzymes play similar roles. We purified to homogeneity the recombinant
      ADP-glucose pyrophosphorylase from N. europaea and characterized its kinetic,
      regulatory, and oligomeric properties. The enzyme was allosterically activated by
      pyruvate, oxaloacetate, and phosphoenolpyruvate and inhibited by AMP. It had a
      broad thermal and pH stability and used different divalent metal ions as
      cofactors. Depending on the cofactor, the enzyme was able to accept different
      nucleotides and sugar phosphates as alternative substrates. However,
      characterization of the recombinant glycogen synthase showed that only ADP-Glc
      elongates the polysaccharide, indicating that ATP and glucose-1-phosphate are the
      physiological substrates of the ADP-glucose pyrophosphorylase. The distinctive
      properties with respect to selectivity for substrates and activators of the ADP
      glucose pyrophosphorylase were in good agreement with the metabolic routes
      operating in N. europaea, indicating an evolutionary adaptation. These unique
      properties place the enzyme in a category of its own within the family,
      highlighting the unique regulation in these organisms.

PMID- 22961848
TI  - Training the Biofilm Generation--a tribute to J. W. Costerton.

PMID- 22961849
TI  - Leptospiral outer membrane protein microarray, a novel approach to identification
      of host ligand-binding proteins.
AB  - Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic
      spirochetes belonging to the genus Leptospira. The leptospiral life cycle
      involves transmission via freshwater and colonization of the renal tubules of
      their reservoir hosts. Infection requires adherence to cell surfaces and
      extracellular matrix components of host tissues. These host-pathogen interactions
      involve outer membrane proteins (OMPs) expressed on the bacterial surface. In
      this study, we developed an Leptospira interrogans serovar Copenhageni strain
      Fiocruz L1-130 OMP microarray containing all predicted lipoproteins and
      transmembrane OMPs. A total of 401 leptospiral genes or their fragments were
      transcribed and translated in vitro and printed on nitrocellulose-coated glass
      slides. We investigated the potential of this protein microarray to screen for
      interactions between leptospiral OMPs and fibronectin (Fn). This approach
      resulted in the identification of the recently described fibronectin-binding
      protein, LIC10258 (MFn8, Lsa66), and 14 novel Fn-binding proteins, denoted
      Microarray Fn-binding proteins (MFns). We confirmed Fn binding of purified
      recombinant LIC11612 (MFn1), LIC10714 (MFn2), LIC11051 (MFn6), LIC11436 (MFn7),
      LIC10258 (MFn8, Lsa66), and LIC10537 (MFn9) by far-Western blot assays. Moreover,
      we obtained specific antibodies to MFn1, MFn7, MFn8 (Lsa66), and MFn9 and
      demonstrated that MFn1, MFn7, and MFn9 are expressed and surface exposed under in
      vitro growth conditions. Further, we demonstrated that MFn1, MFn4 (LIC12631,
      Sph2), and MFn7 enable leptospires to bind fibronectin when expressed in the
      saprophyte, Leptospira biflexa. Protein microarrays are valuable tools for high
      throughput identification of novel host ligand-binding proteins that have the
      potential to play key roles in the virulence mechanisms of pathogens.

PMID- 22961850
TI  - Analysis of ThiC variants in the context of the metabolic network of Salmonella
      enterica.
AB  - In bacteria, the 4-amino-hydroxymethyl-2-methylpyrimidine (HMP) moiety of
      thiamine is synthesized from 5-aminoimidazole ribotide (AIR), a branch point
      metabolite of purine and thiamine biosynthesis. ThiC is a member of the radical S
      adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical
      rearrangement of AIR to HMP-P. As reconstituted in vitro, the ThiC reaction
      requires AdoMet, AIR, and reductant. This study analyzed variants of ThiC in vivo
      and in vitro to probe the metabolic network surrounding AIR in Salmonella
      enterica. Several variants of ThiC that required metabolic perturbations to
      function in vivo were biochemically characterized in vitro. Results presented
      herein indicate that the subtleties of the metabolic network have not been
      captured in the current reconstitution of the ThiC reaction.

PMID- 22961851
TI  - Directional evolution of Chlamydia trachomatis towards niche-specific adaptation.
AB  - On behalf of the host-pathogen "arms race," a cutting-edge approach for
      elucidating genotype-phenotype relationships relies on the identification of
      positively selected loci involved in pathoadaptation. We studied the obligate
      intracellular bacterium Chlamydia trachomatis, for which same-species strains
      display a nearly identical core and pan genome, while presenting a wide range of
      tissue tropism and ecological success. We sought to evaluate the evolutionary
      patterns underlying species separation (divergence) and C. trachomatis serovar
      radiation (polymorphism) and to establish genotype-phenotype associations. By
      analyzing 60 Chlamydia strains, we detected traces of Muller's ratchet as a
      result of speciation and identified positively selected genes and codons
      hypothetically involved in the infection of different human cell types (e.g.,
      columnar epithelial cells of ocular or genital mucosae and mononuclear
      phagocytes) and also events likely driving pathogenic and ecological success
      dissimilarities. In general, these genes code for proteins involved in immune
      response elicitation, proteolysis, and the subversion of host-cell functions, and
      also for proteins with unknown function(s). Several genes are potentially
      involved in more than one adaptive process, suggesting multiple functions or a
      distinct modus operandi for a specific function, and thus should be considered as
      crucial research targets. In addition, six of the nine genes encoding the
      putative antigen/adhesin polymorphic membrane proteins seem to be under positive
      selection along specific serovars, which sustains an essential biological role of
      this extra-large paralogue family in chlamydial pathobiology. This study provides
      insight into how evolutionary inferences illuminate ecological processes such as
      adaptation to different niches, pathogenicity, or ecological success driven by
      arms races.

PMID- 22961852
TI  - SurA is involved in the targeting to the outer membrane of a Tat signal sequence
      anchored protein.
AB  - The twin arginine translocation (Tat) pathway exports folded proteins from the
      cytoplasm to the periplasm of bacteria. The targeting of the exported proteins to
      the Tat pathway relies on a specific amino-terminal signal sequence, which is
      cleaved after exportation. In the phytopathogen Dickeya dadantii, the pectin
      lyase homologue PnlH is exported by the Tat pathway without cleavage of its
      signal sequence, which anchors PnlH into the outer membrane. In proteobacteria,
      the vast majority of outer membrane proteins consists of beta-barrel proteins and
      lipoproteins. Thus, PnlH represents a new kind of outer membrane protein. In
      Escherichia coli, periplasmic chaperones SurA, Skp, and DegP work together with
      the beta-barrel assembly machinery (Bam) to target and insert beta-barrel
      proteins into the outer membrane. In this work, we showed that SurA is required
      for an efficient targeting of PnlH to the outer membrane. Moreover, we were able
      to detect an in vitro interaction between SurA and the PnlH signal sequence.
      Since the PnlH signal sequence contains a highly hydrophobic region, we propose
      that SurA protects it from the hydrophobic periplasm during targeting of PnlH to
      the outer membrane. We also studied the nature of the information carried by the
      PnlH signal sequence responsible for its targeting to the outer membrane after
      exportation by the Tat system.

PMID- 22961853
TI  - Hyperosmotic stress response of Campylobacter jejuni.
AB  - The diarrheal pathogen Campylobacter jejuni and other gastrointestinal bacteria
      encounter changes in osmolarity in the environment, through exposure to food
      processing, and upon entering host organisms, where osmotic adaptation can be
      associated with virulence. In this study, growth profiles, transcriptomics, and
      phenotypic, mutant, and single-cell analyses were used to explore the effects of
      hyperosmotic stress exposure on C. jejuni. Increased growth inhibition correlated
      with increased osmotic concentration, with both ionic and nonionic stressors
      inhibiting growth at 0.620 total osmol liter(-1). C. jejuni adaptation to a range
      of osmotic stressors and concentrations was accompanied by severe filamentation
      in subpopulations, with microscopy indicating septum formation and phenotypic
      diversity between individual cells in a filament. Population heterogeneity was
      also exemplified by the bifurcation of colony morphology into small and large
      variants on salt stress plates. Flow cytometry of C. jejuni harboring green
      fluorescent protein (GFP) fused to the ATP synthase promoter likewise revealed
      bimodal subpopulations under hyperosmotic stress. We also identified frequent
      hyperosmotic stress-sensitive variants within the clonal wild-type population
      propagated on standard laboratory medium. Microarray analysis following
      hyperosmotic upshift revealed enhanced expression of heat shock genes and genes
      encoding enzymes for synthesis of potential osmoprotectants and cross-protective
      induction of oxidative stress genes. The capsule export gene kpsM was also
      upregulated, and an acapsular mutant was defective for growth under hyperosmotic
      stress. For C. jejuni, an organism lacking most conventional osmotic response
      factors, these data suggest an unusual hyperosmotic stress response, including
      likely "bet-hedging" survival strategies relying on the presence of stress-fit
      individuals in a heterogeneous population.

PMID- 22961854
TI  - A conserved UDP-glucose dehydrogenase encoded outside the hasABC operon
      contributes to capsule biogenesis in group A Streptococcus.
AB  - Group A Streptococcus (GAS) is a human-specific bacterial pathogen responsible
      for serious morbidity and mortality worldwide. The hyaluronic acid (HA) capsule
      of GAS is a major virulence factor, contributing to bloodstream survival through
      resistance to neutrophil and antimicrobial peptide killing and to in vivo
      pathogenicity. Capsule biosynthesis has been exclusively attributed to the
      ubiquitous hasABC hyaluronan synthase operon, which is highly conserved across
      GAS serotypes. Previous reports indicate that hasA, encoding hyaluronan synthase,
      and hasB, encoding UDP-glucose 6-dehydrogenase, are essential for capsule
      production in GAS. Here, we report that precise allelic exchange mutagenesis of
      hasB in GAS strain 5448, a representative of the globally disseminated M1T1
      serotype, did not abolish HA capsule synthesis. In silico whole-genome screening
      identified a putative HasB paralog, designated HasB2, with 45% amino acid
      identity to HasB at a distant location in the GAS chromosome. In vitro enzymatic
      assays demonstrated that recombinant HasB2 is a functional UDP-glucose 6
      dehydrogenase enzyme. Mutagenesis of hasB2 alone slightly decreased capsule
      abundance; however, a DeltahasB DeltahasB2 double mutant became completely
      acapsular. We conclude that HasB is not essential for M1T1 GAS capsule biogenesis
      due to the presence of a newly identified HasB paralog, HasB2, which most likely
      resulted from gene duplication. The identification of redundant UDP-glucose 6
      dehydrogenases underscores the importance of HA capsule expression for M1T1 GAS
      pathogenicity and survival in the human host.

PMID- 22961855
TI  - Identification and characterization of five intramembrane metalloproteases in
      Anabaena variabilis.
AB  - Regulated intramembrane proteolysis (RIP) involves cleavage of a transmembrane
      segment of a protein, releasing the active form of a membrane-anchored
      transcription factor (MTF) or a membrane-tethered signaling protein in response
      to an extracellular or intracellular signal. RIP is conserved from bacteria to
      humans and governs many important signaling pathways in both prokaryotes and
      eukaryotes. Proteases that carry out these cleavages are named intramembrane
      cleaving proteases (I-CLips). To date, little is known about I-CLips in
      cyanobacteria. In this study, five putative site-2 type I-Clips (Ava_1070,
      Ava_1730, Ava_1797, Ava_3438, and Ava_4785) were identified through a genome-wide
      survey in Anabaena variabilis. Biochemical analysis demonstrated that these five
      putative A. variabilis site-2 proteases (S2Ps(Av)) have authentic protease
      activities toward an artificial substrate pro-sigma(K), a Bacillus subtilis MTF,
      in our reconstituted Escherichia coli system. The enzymatic activities of
      processing pro-sigma(K) differ among these five S2Ps(Av). Substitution of
      glutamic acid (E) by glutamine (Q) in the conserved HEXXH zinc-coordinated motif
      caused the loss of protease activities in these five S2Ps(Av), suggesting that
      they belonged to the metalloprotease family. Further mapping of the cleaved
      peptides of pro-sigma(K) by Ava_4785 and Ava_1797 revealed that Ava_4785 and
      Ava_1797 recognized the same cleavage site in pro-sigma(K) as SpoIVFB, a cognate
      S2P of pro-sigma(K) from B. subtilis. Taking these results together, we report
      here for the first time the identification of five metallo-intramembrane cleaving
      proteases in Anabaena variabilis. The experimental system described herein should
      be applicable to studies of other RIP events and amenable to developing in vitro
      assays for I-CLips.

PMID- 22961856
TI  - The lysozyme-induced peptidoglycan N-acetylglucosamine deacetylase PgdA (EF1843)
      is required for Enterococcus faecalis virulence.
AB  - Lysozyme is a key component of the innate immune response in humans that provides
      a first line of defense against microbes. The bactericidal effect of lysozyme
      relies both on the cell wall lytic activity of this enzyme and on a cationic
      antimicrobial peptide activity that leads to membrane permeabilization. Among
      Gram-positive bacteria, the opportunistic pathogen Enterococcus faecalis has been
      shown to be extremely resistant to lysozyme. This unusual resistance is explained
      partly by peptidoglycan O-acetylation, which inhibits the enzymatic activity of
      lysozyme, and partly by d-alanylation of teichoic acids, which is likely to
      inhibit binding of lysozyme to the bacterial cell wall. Surprisingly, combined
      mutations abolishing both peptidoglycan O-acetylation and teichoic acid
      alanylation are not sufficient to confer lysozyme susceptibility. In this work,
      we identify another mechanism involved in E. faecalis lysozyme resistance. We
      show that exposure to lysozyme triggers the expression of EF1843, a protein that
      is not detected under normal growth conditions. Analysis of peptidoglycan
      structure from strains with EF1843 loss- and gain-of-function mutations, together
      with in vitro assays using recombinant protein, showed that EF1843 is a
      peptidoglycan N-acetylglucosamine deacetylase. EF1843-mediated peptidoglycan
      deacetylation was shown to contribute to lysozyme resistance by inhibiting both
      lysozyme enzymatic activity and, to a lesser extent, lysozyme cationic
      antimicrobial activity. Finally, EF1843 mutation was shown to reduce the ability
      of E. faecalis to cause lethality in the Galleria mellonella infection model.
      Taken together, our results reveal that peptidoglycan deacetylation is a
      component of the arsenal that enables E. faecalis to thrive inside mammalian
      hosts, as both a commensal and a pathogen.

PMID- 22961857
TI  - Characterization of a ferrous iron-responsive two-component system in nontypeable
      Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHI), an opportunistic pathogen that is
      commonly found in the human upper respiratory tract, has only four identified two
      component signal transduction systems. One of these, an ortholog to the QseBC
      (quorum-sensing Escherichia coli) system, was characterized. This system,
      designated firRS, was found to be transcribed in an operon with a gene encoding a
      small, predicted periplasmic protein with an unknown function, ygiW. The ygiW
      firRS operon exhibited a unique feature with an attenuator present between ygiW
      and firR that caused the ygiW transcript level to be 6-fold higher than the ygiW
      firRS transcript level. FirRS induced expression of ygiW and firR, demonstrating
      that FirR is an autoactivator. Unlike the QseBC system of E. coli, FirRS does not
      respond to epinephrine or norepinephrine. FirRS signal transduction was
      stimulated when NTHI cultures were exposed to ferrous iron or zinc but was
      unresponsive to ferric iron. Notably, the ferrous iron-responsive activation only
      occurred when a putative iron-binding site in FirS and the key phosphorylation
      aspartate in FirR were intact. FirRS was also activated when cultures were
      exposed to cold shock. Mutants in ygiW, firR, and firS were attenuated during
      pulmonary infection, but not otitis media. These data demonstrate that the H.
      influenzae strain 2019 FirRS is a two-component regulatory system that senses
      ferrous iron and autoregulates its own operon.

PMID- 22961859
TI  - The price of tags in protein localization studies.

PMID- 22961858
TI  - A novel component of the Rhodobacter sphaeroides Fla1 flagellum is essential for
      motor rotation.
AB  - Here we describe a novel component essential for flagellar rotation in
      Rhodobacter sphaeroides. This protein is encoded by motF (RSP_0067), the first
      gene of a predicted transcriptional unit which contains two hypothetical genes.
      Sequence analysis indicated that MotF is a bitopic membrane-spanning protein.
      Protease sensitivity assays and green fluorescent protein (GFP) fusions confirmed
      this prediction and allowed us to conclude that the C terminus of MotF is located
      in the periplasmic space. Wild-type cells expressing a functional GFP-MotF fusion
      show a single fluorescent focus per cell. The localization of this protein in
      different genetic backgrounds allowed us to determine that normal localization of
      MotF depends on the presence of FliL and MotB. Characterization of a DeltamotF
      pseudorevertant strain revealed that a single nucleotide change in motB
      suppresses the Mot(-) phenotype of the motF mutant. Additionally, we show that
      MotF also becomes dispensable when other mutant alleles of motB previously
      isolated as second-site suppressors of DeltafliL were expressed in the motF
      mutant strain. These results show that MotF is a new component of the Fla1
      flagellum, which together with FliL is required to promote flagellar rotation,
      possibly through MotB.

PMID- 22961860
TI  - FIPSDock: a new molecular docking technique driven by fully informed swarm
      optimization algorithm.
AB  - The accurate prediction of protein-ligand binding is of great importance for
      rational drug design. We present herein a novel docking algorithm called as
      FIPSDock, which implements a variant of the Fully Informed Particle Swarm (FIPS)
      optimization method and adopts the newly developed energy function of AutoDock
      4.20 suite for solving flexible protein-ligand docking problems. The search
      ability and docking accuracy of FIPSDock were first evaluated by multiple cognate
      docking experiments. In a benchmarking test for 77 protein/ligand complex
      structures derived from GOLD benchmark set, FIPSDock has obtained a successful
      predicting rate of 93.5% and outperformed a few docking programs including
      particle swarm optimization (PSO)@AutoDock, SODOCK, AutoDock, DOCK, Glide, GOLD,
      FlexX, Surflex, and MolDock. More importantly, FIPSDock was evaluated against
      PSO@AutoDock, SODOCK, and AutoDock 4.20 suite by cross-docking experiments of 74
      protein-ligand complexes among eight protein targets (CDK2, ESR1, F2, MAPK14,
      MMP8, MMP13, PDE4B, and PDE5A) derived from Sutherland-crossdock-set. Remarkably,
      FIPSDock is superior to PSO@AutoDock, SODOCK, and AutoDock in seven out of eight
      cross-docking experiments. The results reveal that FIPS algorithm might be more
      suitable than the conventional genetic algorithm-based algorithms in dealing with
      highly flexible docking problems.

PMID- 22961861
TI  - Quantifying the fraction of cirrhosis attributable to alcohol among chronic
      hepatitis C virus patients: implications for treatment cost-effectiveness.
AB  - A substantial baseline risk of liver cirrhosis exists for patients with chronic
      hepatitis C virus (HCV) infection. However, the extent to which this could be
      driven by heavy alcohol use is unclear. Therefore, our principal aim was to
      determine the fraction of cirrhosis attributable to heavy alcohol use among
      chronic HCV patients attending a liver clinic. The study population comprised
      chronic HCV patients who had attended one of five liver clinics in Scotland
      during 1996-2010 and had (1) remained in follow-up for at least 6 months, (2)
      acquired HCV through either injecting drugs or blood transfusion, and (3) an
      estimated date of acquiring infection. Predictors of cirrhosis were determined
      from multivariate logistic regression. Regression parameters were used to
      determine the fraction of cirrhosis attributable to heavy alcohol use. Among
      1,620 patients, 9% were diagnosed with cirrhosis, and 34% had ever engaged in
      heavy alcohol use (>50 units/week for a sustained period). Significant predictors
      of cirrhosis were age, duration of infection, and ever heavy alcohol use. The
      fraction of cirrhosis attributable to ever heavy alcohol use was 36.1% (95%
      confidence interval [CI]: 24.4-47.4). Moreover, among patients who had ever
      engaged in heavy alcohol use specifically, this attributable fraction exceeded
      50% (61.6%; 95% CI: 47.0-72.2). CONCLUSIONS: A substantial proportion of patients
      with chronic HCV develop liver cirrhosis as a consequence of heavy alcohol use.
      This has not been adequately acknowledged by cost utility analyses (CUAs). As
      such, estimates of cost-effectiveness may be exaggerated. Thus, these data are
      important to guide forthcoming CUAs in terms of taking better account of the
      factors leading to cirrhosis among patients with chronic HCV.

PMID- 22961862
TI  - Temporal changes in cardiorespiratory fitness and the incidence of hypertension
      in initially normotensive subjects.
AB  - OBJECTIVES: Low-cardiorespiratory fitness (CRF) has been associated with incident
      hypertension, but whether temporal changes in CRF are associated with incident
      hypertension in initially normotensive subjects are not known. We investigated
      the relationship of baseline CRF and longitudinal changes in CRF with incident
      hypertension in initially normotensive subjects. METHODS: Subjects were 3,831 men
      who participated in two health examinations during 1998-2009. All subjects were
      free of cardiovascular diseases and hypertension at baseline. CRF was directly
      measured by peak oxygen uptake using expired gas analysis during a standard
      treadmill test. RESULTS: During an average of 5 years of follow-up, 373 (9.7%)
      subjects developed hypertension. The incidence of hypertension was inversely
      associated with baseline CRF quartiles [Q1 (lowest) 11.8%, Q2 10.4%, Q3 9.1%, and
      Q4 (highest) 7.5%; P < 0.05 for trend]. The relative risk (RR) of incident
      hypertension in the lowest CRF quartile versus the highest CRF quartile was 1.69
      (95% CI: 1.22-2.34) after adjustment for risk factors. Each metabolic equivalent
      increment higher peak oxygen uptake at baseline examination was associated with
      10% (RR 0.90, 95% CI: 0.83-0.98) lower incidence of hypertension in multivariate
      adjusted model. Subjects whose CRF decreased (<-1.18 ml/kg/min per year) over
      time had a 72% increased risk in developing hypertension (RR 1.72, 95% CI: 1.20
      2.49) compared to subjects with increased CRF (>0.13 ml/kg/min per year) after
      adjustment for risk factors. CONCLUSION: These results demonstrate that both
      baseline CRF levels and changes in CRF over time were associated with the
      incidence of hypertension independent of risk factors.

PMID- 22961863
TI  - High-hole-mobility field-effect transistors based on co-benzobisthiadiazole
      quaterthiophene.
AB  - High-mobility organic thin film transistors based on a benzobisthiadiazole
      containing polymer are presented together with their morphological and optical
      properties. A very tight packing pattern of "edge-on" orientated polymer chains
      is observed in their thin films after annealing, and the hole mobility of this
      polymer is up to 2.5 cm(2)  V(-1)  s(-1) .

PMID- 22961864
TI  - Specificity of IgE antibodies from patients allergic to goat's milk and tolerant
      to cow's milk determined with plasmin-derived peptides of bovine and caprine beta
      caseins.
AB  - SCOPE: Despite a sequence homology of 90% between bovine and caprine beta-caseins
      (CN), IgE antibodies from patients allergic to goat's milk (GM), but tolerant to
      cow's milk (CM), recognize caprine beta-CN without cross-reacting with bovine
      beta-CN. We investigated this lack of cross-reactivity by evaluating the IgE
      reactivity toward peptides isolated from plasmin hydolysates of bovine and
      caprine beta-CN. METHODS AND RESULTS: The IgE-binding capacity of plasmin-derived
      peptides was evaluated with sera from 10 CM-allergic patients and 12 GM
      allergic/CM-tolerant patients. In CM-allergic patients, IgE reactivity of caprine
      fragments (f29-107) and (f108-207), but not (f1-28), was similar to that of the
      bovine counterparts. In contrast, all bovine fragments were poorly recognized by
      IgE antibodies from GM-allergic/CM-tolerant patients. The peptide (f29-107) was
      generally the most immunoreactive fragment of caprine beta-CN. By using synthetic
      peptides, the immunodominant IgE-binding epitope recognized by most GM
      allergic/CM-tolerant patients was located in the caprine domain 49-79.
      CONCLUSION: The restricted specificity of the IgE response toward the caprine
      beta-CN in GM-allergic/CM-tolerant patients is mainly directed against the domain
      49-79, which differs from its bovine counterpart by only three amino acid
      substitutions.

PMID- 22961865
TI  - Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in
      ovine severe sepsis.
AB  - Vasopressin analogs are used as a supplement to norepinephrine in septic shock.
      The isolated effects of vasopressin agonists on sepsis-induced vascular
      dysfunction, however, remain controversial. Because V(2)-receptor stimulation
      induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)
      receptor selectivity might be advantageous. We therefore hypothesized that a
      sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin
      (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment
      of vascular and cardiopulmonary dysfunction in methicillin resistant
      staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of
      hemodynamic instability, awake, chronically instrumented, mechanically
      ventilated, and fluid resuscitated sheep were randomly assigned to receive
      continuous infusions of either POV, AVP, or saline solution (control; each n =
      6). AVP and POV were titrated to maintain mean arterial pressure above baseline -
      10 mmHg. When compared with that of control animals, AVP and POV reduced
      neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma
      levels of nitric oxide, resulting in higher mean arterial pressures and a reduced
      vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary
      bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV
      stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP,
      reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF,
      and angiopoietin-2, thereby leading to an abolishment of cumulative fluid
      accumulation (POV, 9 +/- 15 ml/kg vs. AVP, 110 +/- 13 ml/kg vs. control, 213 +/-
      16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left
      ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals.
      Highly selective V(1a)-agonism appears to be superior to unselective vasopressin
      analogs for the treatment of sepsis-induced vascular dysfunction.

PMID- 22961866
TI  - Left ventricular vortex formation is unaffected by diastolic impairment.
AB  - Normal left ventricular (LV) filling occurs rapidly early in diastole caused by a
      progressive pressure gradient within the ventricle and with a low left atrial
      pressure. This normal diastolic function is altered in patients with heart
      failure. Such impairment of diastolic filling is manifested as an abrupt
      deceleration of the early filling wave velocity. Although variations within the
      early filling wave have been observed previously, the underlying hydrodynamic
      mechanisms are not well understood. Previously, it was proposed that the mitral
      annulus vortex ring formation time was the total duration of early diastolic
      filling and provided a measure of the efficiency of diastolic filling. However,
      we found that the favorable LV pressure difference driving early diastolic
      filling becomes zero simultaneously with the deceleration of the early filling
      wave propagation velocity and pinch-off of the LV vortex ring. Thus we calculated
      the vortex ring formation time using the duration of the early diastolic filling
      wave from its initiation to the time of the early filling wave propagation
      velocity deceleration when pinch-off occurs. This formation time does not vary
      with decreasing intraventricular pressure difference or with degree of diastolic
      dysfunction. Thus we conclude the vortex ring pinch-off occurs before the
      completion of early diastole, and its formation time remains invariant to changes
      of diastolic function.

PMID- 22961868
TI  - The head and neck muscles of the serval and tiger: homologies, evolution, and
      proposal of a mammalian and a veterinary muscle ontology.
AB  - Here we describe the head and neck muscles of members of the two extant felid
      subfamilies (Leptailurus serval: Felinae; Panthera tigris: Pantherinae) and
      compare these muscles with those of other felids, other carnivorans (e.g.,
      domestic dogs), other eutherian mammals (e.g., rats, tree-shrews and modern
      humans), and noneutherian mammals including monotremes. Another major goal of the
      article is to discuss and help clarify nomenclatural discrepancies found in the
      Nomina Anatomica Veterinaria and in veterinary atlases and textbooks that use
      cats and dogs as models to understand the anatomy of domestic mammals and to
      stress differences with modern humans. We propose a unifying nomenclature that is
      expanded to all the head and neck muscles and to all mammalian taxa in order to
      help build veterinary and mammalian muscle ontologies. Our observations and
      comparisons and the specific use of this nomenclature point out that felids such
      as tigers and servals and other carnivorans such as dogs have more facial muscle
      structures related to the mobility of both the auricular and orbital regions than
      numerous other mammals, including modern humans, which might be the result of an
      ancient adaptation related to the remarkable predatory capacities of carnivorans.
      Interestingly, the skeletal differences, mainly concerning the hyoid apparatus,
      pharynx, and larynx, that are likely associated with the different types of
      vocalizations seen in the Felinae (mainly purring) and Pantherinae (mainly
      roaring) are not accompanied by clear differences in the musculature connected to
      these structures in the feline L. serval and the pantherine P. tigris.

PMID- 22961867
TI  - A differing role of oxidative stress in the regulation of central and peripheral
      hemodynamics during exercise in heart failure.
AB  - This study sought to characterize the role of free radicals in regulating central
      and peripheral hemodynamics at rest and during exercise in patients with heart
      failure (HF). We examined cardiovascular responses to dynamic handgrip exercise
      (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral
      antioxidant cocktail (AOC) consisting of vitamin C, E, and alpha-lipoic acid in a
      balanced, crossover design. Central and peripheral hemodynamics, mean arterial
      pressure, cardiac index, systemic vascular resistance (SVR), brachial artery
      blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10
      HF patients and 10 age-matched controls. Blood assays evaluated markers of
      oxidative stress and efficacy of the AOC. When compared with controls, patients
      with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%),
      and evidence of endogenous antioxidant compensation, measured by greater
      superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%)
      in both the HF patients and controls, but significant systemic hemodynamic
      effects were only evident in the patients with HF, both at rest and throughout
      exercise. Specifically, the AOC reduced mean arterial pressure (-5%) and SVR (
      12%) and increased cardiac index (+7%) at each workload. In contrast,
      peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC.
      In conclusion, these data imply that SVR in patients with HF is, at least in
      part, mediated by oxidative stress. However, this finding does not appear to be
      the direct result of muscle-specific changes in PVR.

PMID- 22961869
TI  - Adaptive Markov chain Monte Carlo forward projection for statistical analysis in
      epidemic modelling of human papillomavirus.
AB  - A Bayesian statistical model and estimation methodology based on forward
      projection adaptive Markov chain Monte Carlo is developed in order to perform the
      calibration of a high-dimensional nonlinear system of ordinary differential
      equations representing an epidemic model for human papillomavirus types 6 and 11
      (HPV-6, HPV-11). The model is compartmental and involves stratification by age,
      gender and sexual-activity group. Developing this model and a means to calibrate
      it efficiently is relevant because HPV is a very multi-typed and common sexually
      transmitted infection with more than 100 types currently known. The two types
      studied in this paper, types 6 and 11, are causing about 90% of anogenital warts.
      We extend the development of a sexual mixing matrix on the basis of a formulation
      first suggested by Garnett and Anderson, frequently used to model sexually
      transmitted infections. In particular, we consider a stochastic mixing matrix
      framework that allows us to jointly estimate unknown attributes and parameters of
      the mixing matrix along with the parameters involved in the calibration of the
      HPV epidemic model. This matrix describes the sexual interactions between members
      of the population under study and relies on several quantities that are a priori
      unknown. The Bayesian model developed allows one to estimate jointly the HPV-6
      and HPV-11 epidemic model parameters as well as unknown sexual mixing matrix
      parameters related to assortativity. Finally, we explore the ability of an
      extension to the class of adaptive Markov chain Monte Carlo algorithms to
      incorporate a forward projection strategy for the ordinary differential equation
      state trajectories. Efficient exploration of the Bayesian posterior distribution
      developed for the ordinary differential equation parameters provides a challenge
      for any Markov chain sampling methodology, hence the interest in adaptive Markov
      chain methods. We conclude with simulation studies on synthetic and recent actual
      data.

PMID- 22961870
TI  - Efficient differentiation of human iPSC-derived mesenchymal stem cells to
      chondroprogenitor cells.
AB  - Induced pluripotent stem cells (iPSC) hold tremendous potential for personalized
      cell-based repair strategies to treat musculoskeletal disorders. To establish
      human iPSCs as a potential source of viable chondroprogenitors for articular
      cartilage repair, we assessed the in vitro chondrogenic potential of the
      pluripotent population versus an iPSC-derived mesenchymal-like progenitor
      population. We found the direct plating of undifferentiated iPSCs into high
      density micromass cultures in the presence of BMP-2 promoted chondrogenic
      differentiation, however these conditions resulted in a mixed population of cells
      resembling the phenotype of articular cartilage, transient cartilage, and
      fibrocartilage. The progenitor cells derived from human iPSCs exhibited
      immunophenotypic features of mesenchymal stem cells (MSCs) and developed along
      multiple mesenchymal lineages, including osteoblasts, adipocytes, and
      chondrocytes in vitro. The data indicate the derivation of a mesenchymal stem
      cell population from human iPSCs is necessary to limit culture heterogeneity as
      well as chondrocyte maturation in the differentiated progeny. Moreover, as
      compared to pellet culture differentiation, BMP-2 treatment of iPSC-derived MSC
      like (iPSC-MSC) micromass cultures resulted in a phenotype more typical of
      articular chondrocytes, characterized by the enrichment of cartilage-specific
      type II collagen (Col2a1), decreased expression of type I collagen (Col1a1) as
      well as lack of chondrocyte hypertrophy. These studies represent a first step
      toward identifying the most suitable iPSC progeny for developing cell-based
      approaches to repair joint cartilage damage.

PMID- 22961871
TI  - Evaluation of critical nutritional parameters and their significance in the
      production of rhamnolipid biosurfactants from Pseudomonas aeruginosa BS-161R.
AB  - Eleven biosurfactant producing bacteria were isolated from different petroleum
      contaminated soil and sludge samples. Among these 11 isolates, two were
      identified as promising, as they reduced the surface tension of culture medium to
      values below 27 mN m(-1) . Besides biosurfactant production property, they
      exhibited good flocculating activity. Microbacterium sp. was identified as a new
      addition to the list of biosurfactant and bioflocculant-producers. Optimization
      of various conditions for rhamnolipid production was carried out for one of the
      promising isolate, Pseudomonas aeruginosa BS-161R. Bioglycerol (2.5%), as a cheap
      renewable carbon source, attained better rhamnolipid yield, while sodium nitrate
      appeared to be the preferable nitrogen source. The optimum carbon to nitrogen
      (C/N) and carbon to iron (C/Fe) ratios achieved were 15 and 28,350, respectively,
      which favored rhamnolipid production. Physical parameters like pH, temperature,
      and agitation speed also affected the production of rhamnolipids. Results from
      shake flask optimization indicated that the concentration of bioglycerol, sodium
      nitrate, and iron were the most significant factors affecting rhamnolipid
      production, which was supported by the results of central composite rotatable
      design. After optimization of the culture conditions, the production of
      rhamnolipids increased by ninefold from 0.369 to 3.312 g L(-1) .

PMID- 22961872
TI  - Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as
      warhead.
AB  - Plasmin is best known as the key molecule in the fibrinolytic system, which is
      critical for clot lysis and can initiate matrix metalloproteinase (MMP)
      activation cascade. Along with MMP, plasmin is suggested to be involved in
      physiological processes that are linked to the risk of carcinoma formation.
      Plasmin inhibitors could be perceived as a promising new principle in the
      treatment of diseases triggered by plasmin. On the basis of the peptidic sequence
      derived from the synthetic plasmin substrate, a series of peptidic plasmin
      inhibitors possessing nitrile as warhead were prepared and evaluated for their
      inhibitory activities against plasmin and other serine proteases, plasma
      kallikrein and urokinase. The most potent peptidic inhibitors with the nitrile
      warhead exhibit the potency toward plasmin (IC(50)  = 7.7-11 MUM) and are
      characterized by their selectivity profile against plasma kallikrein and
      urokinase. The results and molecular modeling of the peptidic inhibitor complexed
      with plasmin reveal that the P2 residue makes favorable contacts with the open
      binding pocket comprising the S2 and S3 subsites of plasmin.

PMID- 22961873
TI  - Characterization of the N370S mutant of glucocerebrosidase by hydrogen/deuterium
      exchange mass spectrometry.
AB  - An asparagine-to-serine substitution at residue 370 (N370S) in glucocerebrosidase
      (GCase) is the most prevalent mutation leading to Gaucher's disease, the most
      common lysosomal storage disorder. Two types of hydrogen/deuterium exchange
      experiment coupled with proteolysis and liquid chromatography-mass spectrometry
      (HDX-MS) were used to investigate the dynamic properties and unfolding stability
      of wt, R495H, and N370S GCases in the presence and absence of ligands. R495H
      GCase is used for enzyme replacement therapy and is considered to be a wt
      surrogate, whereas N370S is the most prevalent mutation leading to Gaucher's
      disease. Time-course HDX experiments of the GCases were performed under near
      physiological conditions to detect the protein's local unfolding motions at a
      submolecular level. In guanidine-titration experiments, HDX reactions were
      performed with various concentrations of a chemical denaturant to provide the
      global stability of the proteins. The two types of experiment showed that all
      three purified GCases, wt, R495H, and N370S, have virtually identical local
      unfolding motions and global stabilities in solution. Combined with previous X
      ray crystallographic studies, which showed indistinguishable backbone
      conformations for N370S and R495H GCase mutants and very similar melting
      temperatures for the wt, R495H, and N370S mutants, all three GCases are likely to
      have virtually identical structural and dynamic properties in solution. The
      guanidine-titration experiments revealed that the pharmacological chaperone,
      isofagomine (IFG), interacts more weakly with the N370S mutant than with the
      R495H GCase; this is consistent with the higher IC(50)  value of IFG against
      N370S than against R495H. The time-course experiments showed that IFG restricts
      the local unfolding motions of N370S in the same way as those of R495H when the
      ligand saturates the proteins.

PMID- 22961874
TI  - From an icosahedron to a plane: flattening dodecaiodo-dodecaborate by successive
      stripping of iodine.
AB  - It has been shown by electrospray ionization-ion-trap mass spectrometry that
      B(12)I(12)(2-) converts to an intact B(12) cluster as a result of successive
      stripping of single iodine radicals or ions. Herein, the structure and stability
      of all intermediate B(12)I(n)(-) species (n=11 to 1) determined by means of first
      principles calculations are reported. The initial predominant loss of an iodine
      radical occurs most probably via the triplet state of B(12)I(12)(2-), and the
      reaction path for loss of an iodide ion from the singlet state crosses that from
      the triplet state. Experimentally, the boron clusters resulting from B(12)I(12)(2
      ) through loss of either iodide or iodine occur at the same excitation energy in
      the ion trap. It is shown that the icosahedral B(12) unit commonly observed in
      dodecaborate compounds is destabilized while losing iodine. The boron framework
      opens to nonicosahedral structures with five to seven iodine atoms left. The
      temperature of the ions has a considerable influence on the relative stability
      near the opening of the clusters. The most stable structures with five to seven
      iodine atoms are neither planar nor icosahedral.

PMID- 22961875
TI  - The mineralization inducing peptide derived from dentin sialophosphoprotein for
      bone regeneration.
AB  - Dentin sialophosphoprotein (DSPP) has been shown to play a primary role in the
      formation and growth of hydroxyapatite crystals in an extracellular matrix of
      hard tissue such as bone and teeth. We hypothesized that the mineralization
      ability of DSPP might depend on a specific domain within it. Three peptides,
      which have hydroxyapatite (HA) binding affinity, denoted as mineralization
      inducing peptide (MIP1, MIP2, and MIP3) were identified from DSPP. The both of
      MIP2 and MIP3 had HA nucleation activity demonstrated by XRD. Among three MIPs,
      MIP3 significantly supported the human bone marrow stromal cell differentiation
      into osteoblastic cells. An immunoblot with antibodies specific for the
      phosphorylated forms of ERK was conducted with cells treated by MIP3. MIP3
      transduced intracellular signals via the ERK pathways and was able to induce
      osteoblastic differentiation, as seen by high expression of ALP, type 1 collagen,
      OC, OPN, and Runx2 in accordance with applied MIP3 concentration. The Asp, Glu,
      and Ser residues in MIP3 play important roles for the affinity of calcium in HA
      bone mineral. Further animal experiment with MIP3 in combination with
      hydroxyapatite mineral induced marked new bone formation for 4 weeks at rabbit
      calvarial defect model. The new bone area was much higher in test group, implying
      that the peptide modified group had excellent biocompatibility when compared with
      the unmodified group. Taken together, the MIP from DSPP has potential to enhance
      mineralization followed by to enhance osteoblastic differentiation and bone
      regeneration.

PMID- 22961876
TI  - Comparison of efficacy and safety of intracoronary sodium nitroprusside and
      intravenous adenosine for assessing fractional flow reserve.
AB  - OBJECTIVES: The purpose of this study was to compare the efficacy and safety of
      intracoronary (IC) nitroprusside and intravenous adenosine (IVA) for assessing
      fractional flow reserve (FFR). BACKGROUND: IV infusion of adenosine is a standard
      method to achieve a coronary hyperemia for FFR measurement. However, adenosine is
      expensive, causes multiple side effects, and is contraindicated in patients with
      reactive airway disease. Sodium nitroprusside (NTP) is a strong coronary
      vasodilator but its efficacy and safety for assessing FFR is not well
      established. METHODS: We compared FFR response and side effects profile of IC NTP
      and IVA. Bolus of NTP at a dose of 100 MUg and IVA (140 MUg/kg/min) were used to
      achieve coronary hyperemia. RESULTS: We evaluated 75 lesions in 53 patients (60%
      male) mean age 61.6 +/- 13.9 years. Mean FFR after NTP was similar to FFR after
      adenosine (0.836 +/- 0.107 vs. 0.856 +/- 0.106; P = 0.26; r = 0.91, P < 0.001).
      NTP induced maximal stable hyperemia within 10 sec (mean: 6.4 +/- 1) which lasted
      consistently between 38 and 60 sec (mean 51 +/- 7.5). NTP caused significant
      (14%), but asymptomatic decrease in mean blood pressure which returned to
      baseline within 60 sec. Adenosine caused shortness of breath in 26%, headache and
      flushing in 19%, and transient second degree heart block in 6% of patients. No
      adverse symptoms were reported after NTP. CONCLUSIONS: IC NTP is as effective as
      IVA for measuring FFR. NTP is better tolerated by patients. Since NTP is
      inexpensive, readily available, well tolerated, and safe, it may be a better
      choice for FFR assessment.

PMID- 22961877
TI  - Current-confinement structure and extremely high current density in organic light
      emitting transistors.
AB  - Extremely high current densities are realized in single-crystal ambipolar light
      emitting transistors using an electron-injection buffer layer and a current
      confinement structure via laser etching. Moreover, a linear increase in the
      luminance was observed at current densities of up to 1 kA cm(-2) , which is an
      efficiency-preservation improvement of three orders of magnitude over
      conventional organic light-emitting diodes (OLEDs) at high current densities.

PMID- 22961878
TI  - Optimizing the multimodal approach to pancreatic cyst fluid diagnosis: developing
      a volume-based triage protocol.
AB  - BACKGROUND: The objective of this study was to develop a triage algorithm to
      optimize diagnostic yield from cytology, carcinoembryonic antigen (CEA), and v-Ki
      ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing on different
      components of a single pancreatic cyst fluid specimen. The authors also sought to
      determine whether cell block supernatant was suitable for CEA and KRAS testing.
      METHODS: Fifty-four pancreatic cysts were triaged according to a volume-dependent
      protocol to generate fluid (neat and supernatant) and cell block specimens for
      cytology, comparative CEA, and KRAS testing. Follow-up histology, diagnostic
      cytology, or a combined clinicopathologic interpretation was recorded as the
      final diagnosis. RESULTS: There were 26 mucinous cystic lesions and 28
      nonmucinous cystic lesions with volumes ranging from 0.3 mL to 55 mL. Testing
      different components of the specimens (cell block, neat, and/or supernatant)
      enabled all laboratory investigations to be performed on 50 of 54 cyst fluids
      (92.6%). Interpretive concordance was observed in 17 of 17 cases (100%) and in 35
      of 40 cases (87.5%) that had multiple components tested for CEA and KRAS
      mutations, respectively. An elevated CEA level (>192 ng/mL) was the most
      sensitive test for the detection of a mucinous cystic lesion (62.5%) versus KRAS
      mutation (56%) and "positive" cytology (61.5%). KRAS mutations were identified in
      2 of 25 mucinous cystic lesions (8%) in which cytology and CEA levels were not
      contributory. CONCLUSIONS: A volume-based protocol using different components of
      the specimen was able to optimize diagnostic yield in pancreatic cyst fluids.
      KRAS mutation testing increased diagnostic yield when combined with cytology and
      CEA analysis. The current results demonstrated that supernatant is comparable to
      neat fluid and cell block material for CEA and KRAS testing.

PMID- 22961879
TI  - Concomitant consumption of lycopene and fish oil inhibits tumor growth and
      progression in a mouse xenograft model of colon cancer.
AB  - SCOPE: Our previous report showed that concomitant supplementation of lycopene
      and eicosa-pentaenoic acid synergistically inhibited the proliferation of human
      colon cancer HT-29 cells in vitro. METHODS AND RESULTS: To validate our findings,
      the present study investigated whether consumption of lycopene and fish oil would
      help prevent tumor growth and progression in a mouse xenograft model of colon
      cancer. The inhibitory effects of lycopene and fish oil on tumor growth were
      verified by western blotting analysis, bioluminescent imaging,
      immunohistochemical (IHC) staining and ELISA. The results demonstrated that
      lycopene and fish oil synergistically inhibited the growth of colon cancer in
      tumor-bearing mice. The bioluminescent imaging, histopathological and IHC
      staining results indicated that lycopene and fish oil effectively suppressed
      tumor growth and progression of colon cancer in vivo. The chemopreventive effects
      of lycopene and fish oil were associated with augmented expression of the cell
      cycle inhibitors such as p21(CIP1/WAF1)  and p27(Kip1) , and suppression of
      proliferating cell nuclear antigen, beta-catenin, cyclin D1 and c-Myc proteins.
      Furthermore, lycopene and fish oil inhibited tumor progression through
      suppression of MMP-7, MMP-9, COX-2 and PGE2. CONCLUSION: These results show that
      lycopene and fish oil act synergistically as chemopreventive agents against tumor
      growth and progression in a mouse xenograft model of colon cancer.

PMID- 22961881
TI  - Can we help patients have a better experience? Implementing NICE guidance on
      patient experience.

PMID- 22961880
TI  - Role of the Helicobacter pylori-induced inflammatory response in the development
      of gastric cancer.
AB  - Helicobacter pylori (H. pylori) infection causes chronic gastritis and peptic
      ulceration and is the strongest risk factor for the development of gastric
      cancer. The pathogenesis of H. pylori is believed to be associated with infection
      initiated chronic gastritis, which is characterized by enhanced expression of
      many inflammatory genes. H. pylori utilizes various virulence factors, targeting
      different cellular proteins, to modulate the host inflammatory response. In this
      review, we explore the many different ways by which H. pylori initiates
      inflammation, leveling many "hits" on the gastric mucosa which can lead to the
      development of cancer. We also discuss some recent findings in understanding the
      pathogen-host interactions and the role of transcription factor NF-kappaB in H.
      pylori-induced inflammation.

PMID- 22961882
TI  - Smoking cessation for hospitalised patients: intensive behavioural counselling
      started in hospital and continued after discharge increases quit rates; with
      additional benefit from adding nicotine replacement therapy.

PMID- 22961883
TI  - Bayesian multivariate growth curve latent class models for mixed outcomes.
AB  - In many clinical studies, the disease of interest is multifaceted, and multiple
      outcomes are needed to adequately capture information about the characteristics
      of the disease or its severity. In the analysis of such diseases, it is often
      difficult to determine what constitutes improvement because of the multivariate
      nature of the outcome. Furthermore, when the disease of interest has an unknown
      etiology and/or is primarily a symptom-defined syndrome, there is potential for
      the disease population to have distinct subgroups. Identification of population
      subgroups is of interest as it may assist clinicians in providing appropriate
      treatment or in developing accurate prognoses. We propose multivariate growth
      curve latent class models that group subjects on the basis of multiple symptoms
      measured repeatedly over time. These groups or latent classes are defined by
      distinctive longitudinal profiles of a latent variable, which is used to
      summarize the multivariate outcomes at each point. The mean growth curve for the
      latent variable in each class defines the features of the class. We develop this
      model for any combination of continuous, binary, ordinal, or count outcomes
      within a Bayesian hierarchical framework. We use simulation studies to validate
      the estimation procedures. We apply our model to data from a randomized clinical
      trial evaluating the efficacy of Bacillus Calmette-Guerin in treating symptoms of
      interstitial cystitis where we are able to identify a class of subjects for whom
      treatment is effective.

PMID- 22961884
TI  - Brunner's gland hyperplasia in the sand rat (Psammomys obesus).
AB  - Brunner's glands are submucosal glands located in the proximal duodenum.
      Hyperplasia of the Brunner's gland has been reported rarely in humans and
      animals. We examined sections of the Brunner's gland from 63 sand rats submitted
      for necropsy over 2 years. Of the 63 animals necropsied, 45 (71%) had evidence of
      hyperplasia defined as nodular expansion, dilated ducts, or intraductal papillary
      proliferation. The hyperplasia was graded as mild in 22 (49%) of the cases,
      moderate in 15 (33%), and marked in 8 (18%). We found an association with both
      increased age and evidence of gastric ulceration and hyperplasia of the Brunner's
      gland. In sand rats with marked hyperplasia, 8 of 8 (100%) had evidence of
      gastric ulceration, compared to 13 of 18 (72%) in animals with no hyperplasia.
      Animals with marked hyperplasia were, on average, 8.4 months older than animals
      with no hyperplasia. There was no association with gender. The lesion in sand
      rats is histologically similar to that in humans.

PMID- 22961885
TI  - Gastric lesions in free-ranging black caimans (Melanosuchus niger) associated
      with Brevimulticaecum species.
AB  - The stomachs of 100 free-ranging black caimans (Melanosuchus niger Spix, 1825)
      from the Mamiraua Sustainable Development Reserve, Amazonas state, Brazil, were
      examined for parasitism and pathologic lesions. All animals were harvested for
      human consumption. Ascaridoid nematodes were found in 67 caimans and were
      identified as Brevimulticaecum sp. These parasites were associated with focally
      extensive, chronic gastric ulcers and formation of localized intramural
      granulomas containing nematodes. All caiman were in good nutritional condition,
      which suggests that effects of gastric nematodiasis on the crocodilian hosts were
      minimal at the time of slaughter.

PMID- 22961886
TI  - Light and electron microscopic analysis of consecutive renal biopsy specimens
      from leishmania-seropositive dogs.
AB  - Canine visceral leishmaniasis frequently causes renal damage that leads to
      chronic kidney disease. Fifteen dogs seropositive for Leishmania were selected
      and biopsied before (T0) and 60 days later after (T1) treatment with a specific
      anti-Leishmania pharmacological agent. Various parameters were selected for
      evaluating the glomerular and tubulointerstitial damage. At T0,
      mesangioproliferative and membranoproliferative glomerulonephritis were observed
      in 6 dogs, chronic glomerulosclerosis in 5, and end-stage kidney in 3; renal
      tissue from 1 dog was within normal histologic limits. The most frequently
      observed ultrastructural changes were foot-process effacement, thickening of the
      basement membranes, and immune deposits. One dog had mesangial immune deposits at
      T1 that had not been present at T0, so the diagnosis was changed to
      mesangioproliferative glomerulonephritis. In dogs with end-stage kidney, the
      number of obsolescent glomeruli and cystic atrophied glomeruli was increased at
      T1. However, progression of the glomerular lesions was minimal in most dogs.
      Worsening of tubulointerstitial scores was evident in the dogs with the most
      severe lesions at the first biopsy. Progression of the tubulointerstitial damage
      was minimal in the mildly affected dogs, and the interstitial inflammation was
      abated. In conclusion, renal lesions can progress over a 60-day period in canine
      leishmaniasis. A longer period between the renal biopsies would be necessary to
      demonstrate more severe changes. In addition a specific anti-Leishmania treatment
      could have a significant effect in the early stages of the disease. 

PMID- 22961887
TI  - Statistical vs. stochastic experimental design: an experimental comparison on the
      example of protein refolding.
AB  - Optimization of experimental problems is a challenging task in both engineering
      and science. In principle, two different design of experiments (DOE) strategies
      exist: statistical and stochastic methods. Both aim to efficiently and precisely
      identify optimal solutions inside the problem-specific search space. Here, we
      evaluate and compare both strategies on the same experimental problem, the
      optimization of the refolding conditions of the lipase from Thermomyces
      lanuginosus with 26 variables under study. Protein refolding is one of the main
      bottlenecks in the process development for recombinant proteins. Despite
      intensive effort, the prediction of refolding from sequence information alone is
      still not applicable today. Instead, suitable refolding conditions are typically
      derived empirically in large screening experiments. Thus, protein refolding
      should constitute a good performance test for DOE strategies. We compared an
      iterative stochastic optimization applying a genetic algorithm and a standard
      statistical design consisting of a D-optimal screening step followed by an
      optimization via response surface methodology. Our results revealed that only the
      stochastic optimization was able to identify optimal refolding conditions (~1.400
      U g(-1) refolded activity), which were 3.4-fold higher than the standard.
      Additionally, the stochastic optimization proved quite robust, as three
      independent optimizations performed similar. In contrast, the statistical DOE
      resulted in a suboptimal solution and failed to identify comparable activities.
      Interactions between process variables proved to be pivotal for this
      optimization. Hence, the linear screening model was not able to identify the most
      important process variables correctly. Thereby, this study highlighted the limits
      of the classic two-step statistical DOE.

PMID- 22961888
TI  - Mapping the mechanism of the resorcinol ring formation catalyzed by ArsB, a type
      III polyketide synthase from Azotobacter vinelandii.
AB  - Who's first? Aldol cyclization occurs before hydrolysis in the resorcinol ring
      formation catalyzed by the type III polyketide synthase, ArsB. Synthetic C(20)
      TKA was not converted to alkylresorcinol by ArsB, but rather inhibited the enzyme
      activity, thus indicating that C(20)-TKA is not an intermediate in ArsB-catalyzed
      alkylresorcinol formation.

PMID- 22961889
TI  - Supramolecular chirality in organo-, hydro-, and metallogels derived from bis
      amides of L-(+)-tartaric acid: formation of highly aligned 1D silica fibers and
      evidence of 5-c net SnS topology in a metallogel network.
AB  - A series of bis-amides derived from L-(+)-tartaric acid was synthesized as
      potential low-molecular-weight gelators. Out of 14 bis-amides synthesized, 13
      displayed organo-, hydro-, and ambidextrous gelation behavior. The gels were
      characterized by methods including circular dichroism, differential scanning
      calorimetry, optical and electron microscopy, and rheology. One of the gels
      derived from di-3-pyridyltartaramide (D-3-PyTA) displayed intriguing nanotubular
      morphology of the gel network, which was exploited as a template to generate
      highly aligned 1D silica fibers. The gelator D-3-PyTA was also exploited to
      generate metallogels by treatment with various Cu(II) /Zn(II)  salts under
      suitable conditions. A structure-property correlation on the basis of single
      crystal and powder X-ray diffraction data was attempted to gain insight into the
      structures of the gel networks in both organo- and metallogels. Such study led to
      the determination of the gel-network structure of the Cu(II)  coordination
      polymer-based metallogel, which displayed a 2D sheet architecture made of a
      chloride-bridged double helix that resembled a 5-c net SnS topology.

PMID- 22961890
TI  - Measuring the kinetics and activity of adsorbed proteins: in vitro lysozyme
      deposited onto hydrogel contact lenses over short time periods.
AB  - A new process has been developed to determine the biological activity of an
      intact layer of lysozyme deposited onto a biomaterial surface. This process is
      applied to a number of common hydrogel contact lenses. The activity of the
      surface-adsorbed protein is measured using a standard micrococcal activity assay,
      with extra steps to distinguish between protein on the surface and protein in
      solution. This is in contrast to protein extraction work in which the activity of
      all adsorbed protein is measured. For ionic materials, which are known to deposit
      large amounts of protein, particularly positively charged proteins such as
      lysozyme, there is evidence for loosely bound protein re-entering the solution,
      thus making it impossible to truly separate out the surface-adsorbed protein.
      This optimized process provides the first quantification of the biological
      activity of an intact layer of surface-adsorbed protein at a hydrogel interface.

PMID- 22961891
TI  - Aerosol-assisted molten salt synthesis of NaInS(2) nanoplates for use as a new
      photoanode material.
AB  - NaInS(2) , a H(2) -evolving photocatalyst, is synthesized as single-crystalline
      hexagonal plates by coupling a molten salt synthesis with ultrasonic spray
      pyrolysis (USP) for the first time. USP NaInS(2)  films are used as a new
      photoanode material and have an initial photocurrent of ~37 MUA/cm(2)  upon
      illumination and activities 25 times greater than films made from a standard non
      aerosol NaInS(2)  sample.

PMID- 22961892
TI  - The challenge of regulating agricultural ceftiofur use to slow the emergence of
      resistance to extended-spectrum cephalosporins.

PMID- 22961893
TI  - Differences in colonization and shedding patterns after oral challenge of cattle
      with three Escherichia coli O157:H7 strains.
AB  - Experimental oral challenge studies with three different genotypes of Escherichia
      coli O157:H7 were conducted in cattle to determine the genotype-specific
      variability in shedding frequencies and concentrations and the frequency and
      extent of contamination of the environment. The results indicated that the E.
      coli O157:H7 genotype and ecological origin maybe important factors for the
      occurrence and concentration in the cattle host. Four groups of six young
      Holstein steers each were orally challenged with 10(6) CFU of one of three E.
      coli O157:H7 strains: FRIK 47 (groups 1 and 2), FRIK 1641 (group 3), and FRIK
      2533 (group 4). Recto-anal mucosal swabs (RAMS) and environmental samples were
      taken on alternate days over 30 days. The numbers of E. coli O157:H7 cells and
      generic E. coli cells per sample were determined. Also, the presence and absence
      of 28 gene targets were determined for 2,411 isolates using high-throughput real
      time PCR. Over the study period, strains FRIK 47, FRIK 1641, and FRIK 2533 were
      detected in 52%, 42%, and 2% of RAMS, respectively. Environmental detection of
      the challenge strains was found mainly in samples of the hides and pen floors,
      with strains FRIK 47, FRIK 1641, and FRIK 2533 detected in 22%, 27%, and 0% of
      environmental samples, respectively. Based on the panel of 28 gene targets,
      genotypes of enterohemorrhagic E. coli (EHEC) and generic E. coli from the
      experimental samples were clustered into three subgroups. In conclusion, the
      results suggested that the type and intensity of measures to control this
      pathogen at the preharvest level may need to be strain specific.

PMID- 22961895
TI  - High prevalence and species diversity of Helicobacter spp. detected in wild house
      mice.
AB  - PCR diagnostics detected 100% prevalence of Helicobacter in 425 wild house mice
      (Mus musculus) from across central Europe. Of seven species identified, the five
      most frequent were Helicobacter rodentium (78%), H. typhlonius (53%), H.
      hepaticus (41%), H. bilis (30%), and H. muridarum (1%). Double infections were
      more common (42%) than single (30%) and triple (21%) infections. Wild house mice
      could be considered potential reservoirs of Helicobacter strains for both humans
      and other vertebrates.

PMID- 22961894
TI  - Whole-genome microarray and gene deletion studies reveal regulation of the
      polyhydroxyalkanoate production cycle by the stringent response in Ralstonia
      eutropha H16.
AB  - Poly(3-hydroxybutyrate) (PHB) production and mobilization in Ralstonia eutropha
      are well studied, but in only a few instances has PHB production been explored in
      relation to other cellular processes. We examined the global gene expression of
      wild-type R. eutropha throughout the PHB cycle: growth on fructose, PHB
      production using fructose following ammonium depletion, and PHB utilization in
      the absence of exogenous carbon after ammonium was resupplied. Our results
      confirm or lend support to previously reported results regarding the expression
      of PHB-related genes and enzymes. Additionally, genes for many different cellular
      processes, such as DNA replication, cell division, and translation, are
      selectively repressed during PHB production. In contrast, the expression levels
      of genes under the control of the alternative sigma factor sigma(54) increase
      sharply during PHB production and are repressed again during PHB utilization.
      Global gene regulation during PHB production is strongly reminiscent of the gene
      expression pattern observed during the stringent response in other species.
      Furthermore, a ppGpp synthase deletion mutant did not show an accumulation of
      PHB, and the chemical induction of the stringent response with DL-norvaline
      caused an increased accumulation of PHB in the presence of ammonium. These
      results indicate that the stringent response is required for PHB accumulation in
      R. eutropha, helping to elucidate a thus-far-unknown physiological basis for this
      process.

PMID- 22961896
TI  - Enhancement of acetic acid tolerance in Saccharomyces cerevisiae by
      overexpression of the HAA1 gene, encoding a transcriptional activator.
AB  - Haa1 is a transcriptional activator required for Saccharomyces cerevisiae
      adaptation to weak acids. Here we show that the constitutive HAA1-overexpressing
      strain acquired a higher level of acetic acid tolerance. Under conditions of
      acetic acid stress, the intracellular level of acetic acid was significantly
      lower in HAA1-overexpressing cells than in the wild-type cells.

PMID- 22961897
TI  - Effects of engineered Sinorhizobium meliloti on cytokinin synthesis and tolerance
      of alfalfa to extreme drought stress.
AB  - Cytokinin is required for the initiation of leguminous nitrogen fixation nodules
      elicited by rhizobia and the delay of the leaf senescence induced by drought
      stress. A few free-living rhizobia have been found to produce cytokinin. However,
      the effects of engineered rhizobia capable of synthesizing cytokinin on host
      tolerance to abiotic stresses have not yet been described. In this study, two
      engineered Sinorhizobium strains overproducing cytokinin were constructed. The
      tolerance of inoculated alfalfa plants to severe drought stress was assessed. The
      engineered strains, which expressed the Agrobacterium ipt gene under the control
      of different promoters, synthesized more zeatins than the control strain under
      free-living conditions, but their own growth was not affected. After a 4-week
      inoculation period, the effects of engineered strains on alfalfa growth and
      nitrogen fixation were similar to those of the control strain under nondrought
      conditions. After being subjected to severe drought stress, most of the alfalfa
      plants inoculated with engineered strains survived, and the nitrogenase activity
      in their root nodules showed no apparent change. A small elevation in zeatin
      concentration was observed in the leaves of these plants. The expression of
      antioxidant enzymes increased, and the level of reactive oxygen species decreased
      correspondingly. Although the ipt gene was transcribed in the bacteroids of
      engineered strains, the level of cytokinin in alfalfa nodules was identical to
      that of the control. These findings suggest that engineered Sinorhizobium strains
      synthesizing more cytokinin could improve the tolerance of alfalfa to severe
      drought stress without affecting alfalfa nodulation or nitrogen fixation.

PMID- 22961898
TI  - Increased resistance to multiple antimicrobials and altered resistance gene
      expression in CMY-2-positive Salmonella enterica following a simulated patient
      treatment with ceftriaxone.
AB  - Salmonellosis is one of the most common causes of food-borne disease in the
      United States. Increasing antimicrobial resistance and corresponding increases in
      virulence present serious challenges. Currently, empirical therapy for invasive
      Salmonella enterica infection includes either ceftriaxone or ciprofloxacin (E. L.
      Hohmann, Clin. Infect. Dis. 32:263-269, 2001). The bla(CMY-2) gene confers
      resistance to ceftriaxone, the antimicrobial of choice for pediatric patients
      with invasive Salmonella enterica infections, making these infections especially
      dangerous (J. M. Whichard et al., Emerg. Infect. Dis. 11:1464-1466, 2005). We
      hypothesized that bla(CMY-2)-positive Salmonella enterica would exhibit increased
      MICs to multiple antimicrobial agents and increased resistance gene expression
      following exposure to ceftriaxone using a protocol that simulated a patient
      treatment in vitro. Seven Salmonella enterica strains survived a simulated
      patient treatment in vitro and, following treatment, exhibited a significantly
      increased ceftriaxone MIC. Not only would these isolates be less responsive to
      further ceftriaxone treatment, but because the bla(CMY-2) genes are commonly
      located on large, multidrug-resistant plasmids, increased expression of the
      bla(CMY-2) gene may be associated with increased expression of other drug
      resistance genes located on the plasmid (N. D. Hanson and C. C. Sanders, Curr.
      Pharm. Des. 5:881-894, 1999). The results of this study demonstrate that a
      simulated patient treatment with ceftriaxone can alter the expression of
      antimicrobial resistance genes, including bla(CMY-2) and floR in S. enterica
      serovar Typhimurium and S. enterica serovar Newport. Additionally, we have shown
      increased MICs following a simulated patient treatment with ceftriaxone for
      tetracycline, amikacin, ceftriaxone, and cefepime, all of which have resistance
      genes commonly located on CMY-2 plasmids. The increases in resistance observed
      are significant and may have a negative impact on both public health and
      antimicrobial resistance of Salmonella enterica.

PMID- 22961899
TI  - Pleiotropic control of secondary metabolism and morphological development by
      KsbC, a butyrolactone autoregulator receptor homologue in Kitasatospora setae.
AB  - The gamma-butyrolactone autoregulator signaling cascades have been shown to
      control secondary metabolism and/or morphological development among many
      Streptomyces species. However, the conservation and variation of the regulatory
      systems among actinomycetes remain to be clarified. The genome sequence of
      Kitasatospora setae, which also belongs to the family Streptomycetaceae
      containing the genus Streptomyces, has revealed the presence of three homologues
      of the autoregulator receptor: KsbA, which has previously been confirmed to be
      involved only in secondary metabolism; KsbB; and KsbC. We describe here the
      characterization of ksbC, whose regulatory cluster closely resembles the
      Streptomyces virginiae barA locus responsible for the autoregulator signaling
      cascade. Deletion of the gene ksbC resulted in lowered production of bafilomycin
      and a defect of aerial mycelium formation, together with the early and enhanced
      production of a novel beta-carboline alkaloid named kitasetaline. A putative
      kitasetaline biosynthetic gene cluster was identified, and its expression in a
      heterologous host led to the production of kitasetaline together with JBIR-133,
      the production of which is also detected in the ksbC disruptant, and JBIR-134 as
      novel beta-carboline alkaloids, indicating that these genes were biosynthetic
      genes for beta-carboline alkaloid and thus are the first such genes to be
      discovered in bacteria.

PMID- 22961900
TI  - Lack of direct effects of agrochemicals on zoonotic pathogens and fecal indicator
      bacteria.
AB  - Agrochemicals, fecal indicator bacteria (FIB), and pathogens frequently
      contaminate water simultaneously. No significant direct effects of fertilizer,
      atrazine, malathion, and chlorothalonil on the survival of Escherichia coli,
      Enterococcus faecalis, Salmonella enterica, human polyomaviruses, and adenovirus
      were detected, supporting the assertion that previously observed effects of
      agrochemicals on FIB were indirect.

PMID- 22961901
TI  - Different roles for lactococcal aggregation factor and mucin binding protein in
      adhesion to gastrointestinal mucosa.
AB  - Adhesion of bacteria to mucosal surfaces and epithelial cells is one of the key
      features for the selection of probiotics. In this study, we assessed the adhesion
      property of Lactococcus lactis subsp. lactis BGKP1 based on its strong
      autoaggregation phenotype and the presence of the mucin binding protein (MbpL).
      Genes involved in aggregation (aggL) and possible interaction with mucin (mbpL),
      present on the same plasmid pKP1, were previously separately cloned in the
      plasmid pAZIL. In vivo and in vitro experiments revealed potentially different
      physiological roles of these two proteins in the process of adherence to the
      intestine during the passage of the strain through the gastrointestinal tract. We
      correlated the in vitro and in vivo aggregation of the BGKP1-20 carrying plasmid
      with aggL to binding to the colonic mucus through nonspecific hydrophobic
      interactions. The expression of AggL on the bacterial cell surface significantly
      increased the hydrophobicity of the strain. On the other hand, the presence of
      AggL in the strain reduced its ability to adhere to the ileum. Moreover, MbpL
      protein showed an affinity to bind gastric type mucin proteins such as MUC5AC.
      This protein did not contribute to the binding of the strain to the ileal or
      colonic part of the intestine. Different potential functions of lactococcal AggL
      and MbpL proteins in the process of adhesion to the gastrointestinal tract are
      proposed.

PMID- 22961902
TI  - Impact of vitamin B12 on formation of the tetrachloroethene reductive
      dehalogenase in Desulfitobacterium hafniense strain Y51.
AB  - Corrinoids are essential cofactors of reductive dehalogenases in anaerobic
      bacteria. Microorganisms mediating reductive dechlorination as part of their
      energy metabolism are either capable of de novo corrinoid biosynthesis (e.g.,
      Desulfitobacterium spp.) or dependent on exogenous vitamin B(12) (e.g.,
      Dehalococcoides spp.). In this study, the impact of exogenous vitamin B(12)
      (cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the
      subcellular localization of the reductive PCE dehalogenase was investigated in
      the gram-positive Desulfitobacterium hafniense strain Y51, a bacterium able to
      synthesize corrinoids de novo. PCE-depleted cells grown for several
      subcultivation steps on fumarate as an alternative electron acceptor lost the
      tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of
      the pce gene cluster. In the absence of vitamin B(12), a gradual decrease of the
      PceA activity and protein amount was observed; after 5 subcultivation steps with
      10% inoculum, more than 90% of the enzyme activity and of the PceA protein was
      lost. In the presence of vitamin B(12), a significant delay in the decrease of
      the PceA activity with an ~90% loss after 20 subcultivation steps was observed.
      This corresponded to the decrease in the pceA gene level, indicating that
      exogenous vitamin B(12) hampered the transposition of the pce gene cluster. In
      the absence or presence of exogenous vitamin B(12), the intracellular corrinoid
      level decreased in fumarate-grown cells and the PceA precursor formed
      catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate
      that exogenous vitamin B(12) is not incorporated into the PceA precursor, even
      though it affects the transposition of the pce gene cluster.

PMID- 22961903
TI  - Fe(III) reduction and U(VI) immobilization by Paenibacillus sp. strain 300A,
      isolated from Hanford 300A subsurface sediments.
AB  - A facultative iron-reducing [Fe(III)-reducing] Paenibacillus sp. strain was
      isolated from Hanford 300A subsurface sediment biofilms that was capable of
      reducing soluble Fe(III) complexes [Fe(III)-nitrilotriacetic acid and Fe(III)
      citrate] but unable to reduce poorly crystalline ferrihydrite (Fh). However,
      Paenibacillus sp. 300A was capable of reducing Fh in the presence of low
      concentrations (2 MUM) of either of the electron transfer mediators (ETMs) flavin
      mononucleotide (FMN) or anthraquinone-2,6-disulfonate (AQDS). Maximum initial Fh
      reduction rates were observed at catalytic concentrations (<10 MUM) of either FMN
      or AQDS. Higher FMN concentrations inhibited Fh reduction, while increased AQDS
      concentrations did not. We also found that Paenibacillus sp. 300A could reduce Fh
      in the presence of natural ETMs from Hanford 300A subsurface sediments. In the
      absence of ETMs, Paenibacillus sp. 300A was capable of immobilizing U(VI) through
      both reduction and adsorption. The relative contributions of adsorption and
      microbial reduction to U(VI) removal from the aqueous phase were ~7:3 in PIPES
      [piperazine-N,N'-bis(2-ethanesulfonic acid)] and ~1:4 in bicarbonate buffer. Our
      study demonstrated that Paenibacillus sp. 300A catalyzes Fe(III) reduction and
      U(VI) immobilization and that these reactions benefit from externally added or
      naturally existing ETMs in 300A subsurface sediments.

PMID- 22961905
TI  - Serine-type carboxypeptidase KexA of Aspergillus oryzae has broader substrate
      specificity than Saccharomyces cerevisiae Kex1 and is required for normal hyphal
      growth and conidiation.
AB  - Aspergillus oryzae has an ortholog of Saccharomyces cerevisiae KEX1, termed kexA.
      A truncated form of KexA protein showed serine-type carboxypeptidase activity and
      somewhat broader substrate specificity than Kex1 protease. Furthermore, our
      results indicated that KexA is required for normal growth of A. oryzae and that
      it might be involved in hyphal branching.

PMID- 22961904
TI  - Antimicrobial resistance of Staphylococcus aureus strains acquired by pig farmers
      from pigs.
AB  - Carriage of animal-associated methicillin-resistant Staphylococcus aureus (MRSA)
      clonal complex 398 (CC398) is common among pig farmers. This study was conducted
      (i) to investigate whether pig farmers are colonized with pig-specific S. aureus
      genotypes other than CC398 and (ii) to survey antimicrobial resistance of S.
      aureus isolates from pigs and pig farmers. Forty-eight S. aureus isolates from
      pig farmers and veterinarians and 130 isolates from pigs collected in Western
      Switzerland were genotyped by spa typing and amplified fragment length
      polymorphism (AFLP). Antimicrobial resistance profiles were determined for
      representative sample of the isolates. The data obtained earlier on healthy S.
      aureus carriers without exposure to agriculture were used for comparison. The
      genotype composition of S. aureus isolates from pig farmers and veterinarians was
      similar to isolates from pigs with predominant AFLP clusters CC398, CC9, and
      CC49. The resistance to tetracycline and macrolides (clarithromycin) was common
      among the isolates from farmers and veterinarians (52 and 21%, respectively) and
      similar to resistance levels in isolates from pigs (39 and 23%, respectively).
      This was in contrast to isolates from persons without contact with agriculture,
      where no (0/128) isolates were resistant to tetracycline and 3% of the isolates
      were resistant to clarithromycin. MRSA CC398 was isolated from pigs (n = 11) and
      pig farmers (n = 5). These data imply that zoonotic transmission of multidrug
      resistant S. aureus from pigs to farmers is frequent, and well-known MRSA
      transmission merely represents the tip of the iceberg for this phenomenon. We
      speculate that the relatively low frequency of MRSA isolation is related to lower
      antimicrobial use in Switzerland compared to, for example, the Netherlands.

PMID- 22961906
TI  - Intestinal bacterium Eubacterium cellulosolvens deglycosylates flavonoid C- and O
      glucosides.
AB  - Eubacterium cellulosolvens cleaved the flavone C-glucosides homoorientin and
      isovitexin to their aglycones luteolin and apigenin, respectively. The
      corresponding isomers, orientin and vitexin, or other polyphenolic C-glucosides
      were not deglycosylated. E. cellulosolvens also cleaved several O-coupled
      glucosides of flavones and isoflavones to their corresponding aglycones.

PMID- 22961907
TI  - Bilberries reduce low-grade inflammation in individuals with features of
      metabolic syndrome.
AB  - SCOPE: Low-grade inflammation is a hallmark of cardiometabolic risk. Bilberries
      (Vaccinium myrtillus) are rich in polyphenols with potential anti-inflammatory
      properties. We studied the impact of bilberries on inflammation and gene
      expression profile in peripheral blood mononuclear cells in subjects with
      metabolic syndrome. METHODS AND RESULTS: In randomized, controlled dietary
      intervention, the participants consumed either a diet rich in bilberries (n = 15)
      or a control diet (n = 12). The bilberry group consumed daily an equivalent dose
      of 400 g fresh bilberries, while the control group maintained their habitual
      diet. No differences were found between the groups in body weight, glucose, or
      lipid metabolism, but bilberry supplementation tended to decrease serum high
      sensitivity C-reactive protein, IL-6, IL-12, and LPS concentrations. An
      inflammation score was significantly different between the groups (p = 0.024). In
      transcriptomics analyses (three participants with improved oral glucose tolerance
      test in the bilberry group), Toll-like receptor signaling, cytoplasmic ribosomal
      proteins, and B-cell receptor signaling pathways were differently regulated. QPCR
      analyses (n = 13 and 11 in the bilberry and control groups, respectively) showed
      decreased expression of MMD and CCR2 transcripts associated with monocyte and
      macrophage function associated genes. CONCLUSION: Regular bilberry consumption
      may reduce low-grade inflammation indicating decreased cardiometabolic risk in
      the long term.

PMID- 22961908
TI  - Glycoprotein IIb/IIIa inhibitors with or without thienopyridine pretreatment
      improve outcomes after primary percutaneous coronary intervention in high-risk
      patients with ST elevation myocardial infarction--a meta-regression of randomized
      controlled trials.
AB  - BACKGROUND: Recent studies have casted a doubt on usefulness of routine
      glycoprotein IIb/IIIA inhibitors (GPI) in patients, pretreated with aspirin and
      clopidogrel, undergoing primary percutaneous coronary intervention (PCI) for ST
      elevation myocardial infarction (STEMI). OBJECTIVE: We aimed to investigate the
      effect of relevant factors, particularly thienopyridine pretreatment, on clinical
      benefit from GPI in randomized controlled trials (RCT). METHODS: We searched
      electronic databases for RCT comparing GPI to control in patients with STEMI
      undergoing primary PCI. Relevant study covariates and clinical outcomes were
      extracted. A random effect cumulative and subgroup analyses (thienopyridine non
      pretreated studies vs. pretreated studies) were performed. A weighted random
      effect meta-regression to determine the effect of thienopyridine pretreatment,
      enrollment year, control group mortality, and ischemic time on mortality benefit
      from GPI use was conducted. RESULTS: Twenty studies (9 non-pretreated, 11
      pretreated) with a total of 7,414 patients (3,811 GPI, 3,603 control) were
      included. GPI use reduces mortality (risk ratio, RR = 0.75 95% confidence
      interval (CI) 0.57-0.97, P = 0.03), target vessel revascularization (TVR) (RR =
      0.63, 95% CI 0.50-0.80, P = 0.0002), but not reinfarction (RR = 0.66, 95% CI 0.44
      1.0, P = 0.05) at 30 days. There was no effect of thienopyridine pretreatment on
      reduction in mortality (P = 0.39), reinfarction (P = 0.46), or TVR (P = 0.95) in
      subgroup analysis. Meta-regression analyses showed significant effect of control
      group mortality risk (B = -12.15, P = 0.034) but not of thienopyridine
      pretreatment, enrollment year or control group ischemic time on mortality
      reduction from GPI use. CONCLUSION: The benefit from GPI use in primary PCI for
      STEMI appears to depend on mortality risk, and not on thienopyridine
      pretreatment.

PMID- 22961909
TI  - Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the
      importance of the already established thyroid fusions genes.
AB  - Neoplasms frequently present structural chromosomal aberrations that can alter
      the level of expression of a protein or to the expression of an aberrant chimeric
      protein. In the thyroid, the PAX8-PPARG fusion is present in the neoplastic
      lesions that have a follicular architecture-follicular thyroid carcinoma (FTC)
      and follicular variant of papillary thyroid carcinoma (FVPTC), and less
      frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC
      fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability
      to detect fusion genes is relevant for a correct diagnosis and for therapy. We
      have developed a new fusion gene microarray-based approach for simultaneous
      analysis of all known and predicted fusion gene variants. We did a comprehensive
      screen for 548 known and putative fusion genes in 27 samples of thyroid tumors
      and three positive controls-one thyroid cancer cell line (TPC-1) and two PTCs
      with known CCDC6-RET (alias RET/PTC1) fusion gene, using this microarray. Within
      the thyroid tumors tested, only well known, previously reported fusion genes in
      thyroid oncology were identified. Our results reinforce the pathogenic role
      played by RET/PTC1, RET/PTC3, and PAX8-PPARG fusion genes in thyroid
      tumorigenesis.

PMID- 22961910
TI  - Predictive accuracy of risk factors and markers: a simulation study of the effect
      of novel markers on different performance measures for logistic regression
      models.
AB  - The change in c-statistic is frequently used to summarize the change in
      predictive accuracy when a novel risk factor is added to an existing logistic
      regression model. We explored the relationship between the absolute change in the
      c-statistic, Brier score, generalized R(2) , and the discrimination slope when a
      risk factor was added to an existing model in an extensive set of Monte Carlo
      simulations. The increase in model accuracy due to the inclusion of a novel
      marker was proportional to both the prevalence of the marker and to the odds
      ratio relating the marker to the outcome but inversely proportional to the
      accuracy of the logistic regression model with the marker omitted. We observed
      greater improvements in model accuracy when the novel risk factor or marker was
      uncorrelated with the existing predictor variable compared with when the risk
      factor has a positive correlation with the existing predictor variable. We
      illustrated these findings by using a study on mortality prediction in patients
      hospitalized with heart failure. In conclusion, the increase in predictive
      accuracy by adding a marker should be considered in the context of the accuracy
      of the initial model.

PMID- 22961911
TI  - Recent agents targeting HIF-1alpha for cancer therapy.
AB  - The discovery of hypoxia-inducible factor-1 (HIF-1) has led to an increasing
      understanding of the mechanism of tumor hypoxia in the past two decades. As a key
      transcriptional regulator, HIF-1 plays a central role in the adaptation of tumor
      cells to hypoxia by activating the transcription of targeting genes, which
      regulate several biological processes including angiogenesis, cell proliferation,
      survival, glucose metabolism and migration. The inhibitors of HIF-1 in cancer
      have provided us a new clue for the targeting cancer therapy. This review will
      introduce the general knowledge of the biology characteristic of HIF-1 and
      mechanism of O(2)-dependent regulation. Moreover, a number of chemical inhibitors
      plus protein and nucleic acid inhibitors are included and classified mainly based
      on their different mechanism of inhibiting action. We also prefer to discuss the
      advantages of protein and nucleic acid inhibitors compared with chemical
      inhibitors.

PMID- 22961912
TI  - Shifting up a gear: considerations on assessment and rehabilitation of driving in
      people with neurological conditions. An extended editorial.

PMID- 22961913
TI  - Pancreatic cyst fluid triage: a critical component of the preoperative evaluation
      of pancreatic cysts.

PMID- 22961915
TI  - Three-dimensional pore structure analysis of nano/microfibrous scaffolds using
      confocal laser scanning microscopy.
AB  - Specific internal pore architectures are required to provide the needed
      biological and biophysical functions for fibrous scaffolds as these architectures
      are critical to cell infiltration and in-grows performance. However, the key
      challenging on evaluating 3D pore structure of fibrous scaffolds for better
      understanding the capability of different structures for biological application
      is not well investigated. This article reports a fast, accurate, nondestructive,
      and comprehensive evaluation approach based on confocal laser scanning microscopy
      (CLSM) and three-dimensional image analysis to study the pore structure and
      porosity parameters of Nano/Microfibrous scaffolds. Also a new method of making
      the fiber fluorescent using quantum dots (QDs) was applied before 3D imaging.
      Fibrous scaffolds with different porosity parameters produced by electrospinning
      and their 3D-pore structure was evaluated by this approach and the results were
      compared to results of capillary flow porometry. The pore structural properties
      measured in this approach are in good agreement with that measured by the
      capillary flow porometry (with significant level 0.05). Furthermore, the
      introduced approach can measure the pore interconnectivity of the scaffold.

PMID- 22961914
TI  - Live-cell studies of p300/CBP histone acetyltransferase activity and inhibition.
AB  - Histone acetyltransferase enzymes (HATs) are important therapeutic targets, but
      there are few cell-based assays available for evaluating the pharmacodynamics of
      HAT inhibitors. Here we present the application of a FRET-based reporter, Histac,
      in live-cell studies of p300/CBP HAT inhibition, by both genetic and
      pharmacologic disruption. shRNA knockdown of p300/CBP led to increased Histac
      FRET, thus suggesting a role for p300/CBP in the acetylation of the histone H4
      tail. Additionally, we describe a new p300/CBP HAT inhibitor, C107, and show that
      it can also increase cellular Histac FRET. Taken together, these studies provide
      a live-cell strategy for identifying and evaluating p300/CBP inhibitors.

PMID- 22961916
TI  - Radioiodine therapy in benign thyroid diseases: effects, side effects, and
      factors affecting therapeutic outcome.
AB  - Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago,
      and the patients treated since then are probably numbered in the millions. Fifty
      to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With
      longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease,
      whereas this risk is much lower when treating toxic nodular goiter. The side
      effect causing most concern is the potential induction of ophthalmopathy in
      predisposed individuals. The response to (131)I therapy is to some extent related
      to the radiation dose. However, calculation of an exact thyroid dose is error
      prone due to imprecise measurement of the (131)I biokinetics, and the importance
      of internal dosimetric factors, such as the thyroid follicle size, is probably
      underestimated. Besides these obstacles, several potential confounders interfere
      with the efficacy of (131)I therapy, and they may even interact mutually and
      counteract each other. Numerous studies have evaluated the effect of (131)I
      therapy, but results have been conflicting due to differences in design, sample
      size, patient selection, and dose calculation. It seems clear that no single
      factor reliably predicts the outcome from (131)I therapy. The individual
      radiosensitivity, still poorly defined and impossible to quantify, may be a major
      determinant of the outcome from (131)I therapy. Above all, the impact of (131)I
      therapy relies on the iodine-concentrating ability of the thyroid gland. The
      thyroid (131)I uptake (or retention) can be stimulated in several ways, including
      dietary iodine restriction and use of lithium. In particular, recombinant human
      thyrotropin has gained interest because this compound significantly amplifies the
      effect of (131)I therapy in patients with nontoxic nodular goiter.

PMID- 22961917
TI  - A spirobifluorene-based polymer of intrinsic microporosity with improved
      performance for gas separation.
AB  - A highly gas-permeable polymer with enhanced selectivities is prepared using
      spirobifluorene as the main structural unit. The greater rigidity of this polymer
      of intrinsic microporosity (PIM-SBF) facilitates gas permeability data that lie
      above the 2008 Robeson upper bound, which is the universal performance indicator
      for polymer gas separation membranes.

PMID- 22961918
TI  - Synthesis and temperature-induced morphological control in a hybrid porous iron
      phosphonate nanomaterial and its excellent catalytic activity in the synthesis of
      benzimidazoles.
AB  - A new organic-inorganic hybrid porous iron-phosphonate material, HPFP-1, has been
      synthesized under hydrothermal conditions by using hexamethylenediamine-N,N,N',N'
      tetrakis-(methylphosphonic acid) (HDTMP) as the organophosphorus precursor. The
      morphology of this material was found to be different at three different
      temperatures. The material that was synthesized at 453 K showed a flake-like
      particle morphology and the material was highly crystalline. Whereas, the
      materials that were synthesized at 443 K and 423 K were semi-crystalline and
      showed rod-like- and spherical morphological features, respectively. SEM and TEM
      were employed to understand this change in particle morphology depending on the
      reaction temperature. Powder XRD analysis suggested the formation of a new
      tetragonal phase in HPFP-1 (a=11.313, c=15.825 A; V=2025.659 A(3)). N(2)-sorption
      analysis suggested the existence of supermicropores and interparticle mesopores
      in these materials. Elemental- and thermal analyses, as well as FTIR
      spectroscopy, were employed to verify the composition and framework bonding of
      the material. The HPFP-1 material showed excellent catalytic activity for the
      synthesis of benzimidazole derivatives under mild liquid-phase reaction
      conditions.

PMID- 22961919
TI  - A highly entangled polymeric nanoconstruct assembled by siRNA and its reduction
      triggered siRNA release for gene silencing.
AB  - A nanoconstruct (NC) is developed from a biocompatible natural polymer and siRNA
      conjugates to deliver small interfering RNA (siRNA) target-specifically without
      cationic condensation reagents. This study reports a novel siRNA-mediated cross
      linked NC produced by hybridizing two complementary single-stranded siRNAs that
      are conjugated to the polymer dextran via a disulfide linkage. The reducible
      disulfide bond between the siRNA and polymer allow siRNA release from the NC in
      the reducible cytoplasmic region after the NC enters the cell. In addition, when
      the NC contains the prostate-carcinoma-binding peptide aptamer DUP-1, it can
      selectively deliver siRNA into prostate cancer cells of the PC-3 lines; thus, the
      newly formulated NC has reduced the cytotoxicity and improved the efficacy of
      target-specific siRNA delivery. Moreover, this new concept of NCs using
      biocompatible siRNA and a neutral polymer may provide insightful knowledge for
      future directions for designing NCs for stimuli-responsive and advanced target
      specific siRNA delivery.

PMID- 22961920
TI  - Photoluminescence property of A9B(VO4)7 [A = Ca, Sr, Ba and B = La, Gd]
      phosphors.
AB  - A new efficient phosphor, A9B(VO4)7 [A = Ca, Sr, Ba and B = La, Gd] has been
      synthesized by the solid-state method at high temperature. X-ray diffraction
      analysis confirmed the formation of the compound. Photoluminescence excitation
      measurements show that the phosphor can be efficiently excited by near
      ultraviolet light from 300 nm to 400 nm to realize emission covering the 397-647
      nm region of visible spectrum. Therefore, newly synthesized novel phosphor may be
      useful as green-emitting phosphor in solid-state lighting.

PMID- 22961921
TI  - Synthesis and fabrication of a degradable poly(N-isopropyl acrylamide) scaffold
      for tissue engineering applications.
AB  - Biodegradable poly(N-isopropyl acrylamide) (polyNIPAM) hydrogels with controlled
      molecular weight of the parent polymer and its degradation products were
      synthesized by atom transfer radical polymerization in the presence of a
      polycaprolactone-based di-chlorinated macroinitiator and polycaprolactone
      dimethacrylate. The phase transition temperature, swelling, hydrolytic
      degradability, and mechanical properties at 25 and 37 degrees C were explored. A
      cytocompatibility study showed good NIH3T3 cell response over 5 days culture on
      the surface of the hydrogels, demonstrated by a consistent increase in cell
      proliferation detected by an Alamar Blue assay. MTT [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide] results suggested that the hydrogels and their
      degradation products in the concentration range of 1-25 mg/mL were not cytotoxic
      to NIH3T3 cells. A sphere-templating technique was utilized to fabricate
      biodegradable polyNIPAM scaffolds with monodisperse, pore size. Scaffolds with
      pore diameter of 48 +/- 6 MUm were loaded with A-10 smooth muscle cells and then
      warmed to 37 degrees C entrapping cells in pores approximately 40 MUm in
      diameter, a size we have found to be optimal for angiogenesis and biointegration.
      Due to their degradable nature, tunable molecular weight, highly interconnected
      morphology, thermally controlled monodisperse pore size, and temperature-induced
      volume expansion-contraction, the polyNIPAM-based scaffolds developed in this
      work will be valuable in tissue engineering.

PMID- 22961922
TI  - Craving for cannabis in patients with psychotic disorder, their non-affected
      siblings and healthy controls: psychometric analysis of the obsessive compulsive
      drug use scale.
AB  - Cannabis use is more common in individuals with non-affective psychotic disorder
      and their siblings compared to healthy controls. As cannabis use is associated
      with a greater risk to develop psychotic disorder and an adverse outcome in those
      who already developed psychosis, it is important to know the role of craving in
      continued cannabis use and relapse in these vulnerable subjects. Therefore, we
      examined the validity of the Obsessive Compulsive Drug Use Scale for cannabis
      (OCDUS-CAN) in patients with non-affective psychotic disorder, their siblings,
      and healthy controls who all used cannabis in the past year. Simultaneous
      component analysis (SCA) was used to determine component weights that optimally
      explained the (co)variance of the OCDUS-CAN variables in these different
      populations simultaneously. A three-component SCA solution explained 74.2 % of
      the total variance, and consisted of well-interpretable subscales that could be
      best described as craving/urge, resistance, and impact. Reliability of the
      subscales was good. The three subscales significantly discriminated between
      frequent and infrequent cannabis users. Patients scored higher on the
      craving/urge and impact scale than siblings and controls, which could be related
      to primary and secondary symptoms of their disorder. The OCDUS-CAN is well
      suitable for people with or without vulnerability for psychotic disorder.

PMID- 22961923
TI  - On demand: the singular rht net, an ideal blueprint for the construction of a
      metal-organic framework (MOF) platform.

PMID- 22961924
TI  - Bayesian modeling of time-dependent vulnerability to environmental hazards: an
      example using autism and pesticide data.
AB  - BACKGROUND: Flexible modeling of time-dependent effects is required when
      vulnerability to hazards can be expected to vary over time, but the nature of
      this temporal dependency cannot be specified in advance. We present an analytic
      approach requiring minimal a priori assumptions about temporal parameters and
      producing measures of uncertainty for these parameters. METHODS: As a
      demonstration, we employ data describing autism spectrum disorders and
      applications of organochlorine pesticides in proximity to maternal residence
      before, during, and after pregnancy. We formulate a Bayesian model specifying
      temporal vulnerability as a flexible step function and constrain the dose
      response relationship to be linear. We separately pooled information regarding
      hazard frequency and magnitude among cases and controls and used it as inputs for
      a Metropolis-within-Gibbs algorithm. To assess statistical significance, we
      conduct Monte Carlo simulations based on parameters calculated in the Gibbs
      portion of the algorithm. RESULTS: This method delineated two discrete periods of
      association between hazard and outcome. The first corresponded to a previously
      noted period of vulnerability with the added information of wide credible
      intervals, suggesting a high degree of uncertainty with respect to timing.
      Parameters for the second, previously unobserved period displayed slightly higher
      precision. Assessment of model fit favored the simultaneous inclusion of both
      these periods, and both periods appeared statistically significant on the basis
      of posterior distributions of specific parameters using Monte Carlo simulations.
      CONCLUSIONS: This method enabled a fuller accounting of time-dependent
      associations between hazards and outcomes without specifying temporal structure
      in advance.

PMID- 22961925
TI  - Reactive oxygen species-induced activation of ERK and p38 MAPK mediates PMA
      induced NETs release from human neutrophils.
AB  - Neutrophils/polymorphonuclear leukocytes (PMNs), an important component of innate
      immune system, release extracellular traps (NETs) to eliminate invaded pathogens;
      however understanding of the role of signaling molecules/proteins need to be
      elucidated. In the present study role of p38 MAPK and extracellular signal
      regulated kinase (ERK) against phorbol 12-myristate 13-acetate (PMA) induced
      reactive oxygen species (ROS) generation and NETs formation has been
      investigated. Human neutrophils were treated with PMA to induce free radical
      generation and NETs release, which were monitored by NBT reduction and
      elastase/DNA release, respectively. PMA treatment led to the time dependent
      phosphorylation of p38 MAPK and ERK in PMNs. Pretreatment of PMNs with SB202190
      or U0126 did not significantly reduce PMA induce free radical generation, but
      prevented NETs release. Pretreatment of PMNs with NADPH oxidase inhibitor
      (diphenyleneiodonium chloride) significantly reduced free radical generation, p38
      MAPK and ERK phosphorylation as well as NETs release, suggesting that p38 MAPK
      and ERK activation was downstream to free radical generation. The present study
      thus demonstrates ROS dependent activation of ERK and p38 MAPK, which mediated
      PMA induced NETs release from human neutrophils.

PMID- 22961926
TI  - Crystal structures of BapA complexes with beta-lactam-derived inhibitors
      illustrate substrate specificity and enantioselectivity of beta-aminopeptidases.
AB  - beta-Aminopeptidases have exclusive biocatalytic potential because they react
      with peptides composed of beta-amino acids, which serve as building blocks for
      the design of non-natural peptidomimetics. We have identified the beta-lactam
      antibiotic ampicillin and the ampicillin-derived penicilloic acid as novel
      inhibitors of the beta-aminopeptidase BapA from Sphingosinicella
      xenopeptidilytica (K(i)  values of 0.69 and 0.74 mM, respectively). We report
      high-resolution crystal structures of BapA in noncovalent complexes with these
      inhibitors and with the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl
      fluoride. All three inhibitors showed similar binding characteristics; the
      aromatic moiety extended into a hydrophobic binding pocket of the active site,
      and the free amino group formed a salt bridge with Glu133 of BapA. The exact
      position of the inhibitors and structural details of the ligand binding pocket
      illustrate the specificity and the enantioselectivity of BapA-catalyzed reactions
      with beta-peptide substrates.

PMID- 22961927
TI  - Tautomerization in 2,7,12,17-tetraphenylporphycene and 9-amino-2,7,12,17
      tetraphenylporphycene: influence of asymmetry on the direction of the transition
      moment.
AB  - Femtosecond transient absorption anisotropy studies have been performed for two
      porphycenes of different symmetry. In 2,7,12,17-tetraphenylporphycene, the
      chemical identity of two trans forms implies a change in the S(0)-S(1) transition
      moment direction upon tautomerization. Exploiting this phenomenon, the rates of
      double hydrogen transfer in both the S(0) and S(1) states (1.4*10(12)  s(-1) and
      2.7*10(11)  s(-1) , respectively) have been determined by performing time
      resolved anisotropy studies. In the asymmetric 9-amino-2,7,12,17
      tetraphenylporphycene, tautomerization occurs with a similar rate in the ground
      state. In the S(1) state, the reaction is hindered in its vibrationally relaxed
      form, but the excitation spectra suggest that it may occur for an unrelaxed
      molecule. Unlike all porphycenes that have been studied so far, 9-amino-2,7,12,17
      tetraphenylporphycene does not reveal significant changes in anisotropy owing to
      intramolecular double hydrogen transfer; rather, the transition-moment directions
      are similar in the two tautomeric forms. Analysis of the molecular orbitals
      allows for an explanation of the "locking" of the transition moments: it is due
      to a large splitting of the two HOMO orbitals, which retain the order of their
      energies in the two tautomers.

PMID- 22961928
TI  - Separation and determination of anesthetics by capillary electrophoresis with
      mixed micelles of sodium dodecyl sulfate and Tween 20 using
      electrochemiluminescence detection.
AB  - A simple and new method for the simultaneous determination of procaine (Pro),
      lidocaine (Lid), ropivacaine (Rop) and bupivacaine (Bup) was developed using
      capillary electrophoresis separation with mixed micelles and
      electrochemiluminescence detection. The use of mixed micelles of 2.0 * 10(-3) 
      mol/L sodium dodecyl sulfate (SDS) and 8.0 * 10(-3)  mol/L Tween 20 greatly
      improved separation selectivity. The detection sensitivities of four drugs with a
      Pt working electrode were increased by modification of the Pt electrode with
      europium(III)-doped Prussian Blue analog (Eu-PB). Under optimal conditions, the
      four local anesthetics were well separated and detected. The limits of detection
      (LOD, S/N = 3) of Pro, Lid, Rop and Bup in standard solution are 2.5 * 10(-8) ,
      1.3 * 10(-8) , 3.0 * 10(-8) and 4.1 * 10(-8)  mol/L, respectively. The limits of
      quantitation (LOQ, S/N = 10) of Pro, Lid, Rop and Bup are 2.3 * 10(-7) , 1.2 *
      10(-7) , 3.7 * 10(-7) and 5.6 * 10(-7)  mol/L in a human urine sample, and 8.5 *
      10(-7) , 6.9 * 10(-7) , 2.8 * 10(-6) and 1.1 * 10(-6)  mol/L in a human serum
      sample, respectively. The recoveries of four drugs at different spiked
      concentrations in human urine and serum samples were between 86.5 and 107.6%. The
      proposed method has been successfully applied to determine local anesthetics in
      biofluids.

PMID- 22961929
TI  - Student outcomes associated with use of asynchronous online discussion forums in
      gross anatomy teaching.
AB  - Asynchronous online discussion forums are increasingly common in blended learning
      environments but the relationship to student learning outcomes has not been
      reported for anatomy teaching. Forums were monitored in two multicampus anatomy
      courses; an introductory first year course and a second year physiotherapy
      specific course. The forums are structured with a separate site for each course
      module and moderated weekly by staff. Students are encouraged to post to new
      threads (initial post) and answer queries in threads started by others (reply
      post). Analysis of forums was conducted separately for each course and included
      overall activity (posts and views) for a full semester and a detailed analysis
      for one week in the middle of semester. Students were classified as zero,
      moderate, or high contributors to the forums based on the number of posts. Final
      mark for the course was related to level of forum contribution using
      nonparametric tests. Forum threads were characterized as task-focused,
      administrative, or other. A higher proportion of second year (36%) than first
      year (17%) students posted on the forums and the postings were more likely to be
      task-focused and student initiated. Second-year students that posted frequently
      to the forum gained a higher final mark for the course than those that did not
      post or only posted a moderate number of times (P < 0.01). This relationship was
      not evident for first-year students who had a much higher proportion of
      administrative threads. Forums in anatomy courses can be powerful learning tools
      encouraging deeper learning and improved learning outcomes.

PMID- 22961930
TI  - A review of photocatalysis using self-organized TiO2 nanotubes and other ordered
      oxide nanostructures.
AB  - Photocatalytic approaches, that is the reaction of light-produced charge carriers
      at a semiconductor surface with their environment, currently attract an extremely
      wide scientific interest. This is to a large extent due to the high expectations:
      i) to convert sunlight directly into an energy carrier (H(2)), ii) to stimulate
      chemical synthetic reactions, or iii) to degrade unwanted environmental
      pollutants. Since the early reports in 1972, TiO(2) has been the most
      investigated photocatalytic material by far; this originates from its outstanding
      electronic properties that allow for a wide range of applications. Not only the
      material, but also its structure and morphology, can have a considerable
      influence on the photocatalytic performance of TiO(2). In recent years,
      particularly 1D (or pseudo 1D) structures such as nanowires and nanotubes have
      received great attention. The present Review focuses on TiO(2) nanotube arrays
      (and similar structures) that grow by self-organizing electrochemistry (highly
      aligned) from a Ti metal substrate. Herein, the growth, properties, and
      applications of these tubes are discussed, as well as ways and means to modify
      critical tube properties. Common strategies are addressed to improve the
      performance of photocatalysts such as doping or band-gap engineering, co-catalyst
      decoration, junction formation, or applying external bias. Finally, some unique
      applications of the ordered tube structures in various photocatalytic approaches
      are outlined.

PMID- 22961931
TI  - Musicality: instinct or acquired skill?
AB  - Is the human tendency toward musicality better thought of as the product of a
      specific, evolved instinct or an acquired skill? Developmental and evolutionary
      arguments are considered, along with issues of domain-specificity. The article
      also considers the question of why humans might be consistently and intensely
      drawn to music if musicality is not in fact the product of a specifically evolved
      instinct.

PMID- 22961932
TI  - Photonic multilayer sensors from photo-crosslinkable polymer films.
AB  - Colorimetric temperature sensors are prepared from photo-crosslinkable polymers
      by sequentially spin-coating and crosslinking alternating layers of poly(N
      isopropylacrylamide) and poly(para-methyl styrene). Layer thicknesses and
      copolymer chemistries are chosen to provide robust colorimetric temperature
      sensors that cover nearly the full visible spectrum.

PMID- 22961933
TI  - Is spontaneous reporting always the most important information supporting drug
      withdrawals for pharmacovigilance reasons in France?
AB  - PURPOSE: The objective of our study was to determine the nature of scientific
      evidence leading to drug withdrawal for safety reasons in France (between 2005
      and 2011). METHODS: Drugs (i.e., active ingredients) withdrawn were identified
      from the Web site of the French Health Products Agency. Additional information
      allowed us to classify these withdrawals according to the nature of evidence as
      clinical trials (CT), case reports/case series (CR/CS), case-control studies
      (CC), cohort, animal, or observational studies. RESULTS: A total of 22 active
      ingredients were withdrawn from the French market between 2005 and 2011. The
      nature and type of adverse drug reactions (ADRs) leading more frequently to drug
      withdrawal were cardiovascular (10-fold), neurological (5-fold), or hepatic,
      cutaneous, or psychiatric (3-fold each) ADRs. CR (19/22; 86.4%) and CT (13/22;
      59.1%) were the most frequently involved methods. In 5 of 22 (23%) cases, CR were
      the sole evidence. However, 68% (15/22) of regulatory decisions were based on
      multiple sources of evidence: For example, data from CR + CT were used in eight
      cases. CC or cohort studies were used in only five cases. CONCLUSION: This study
      underlines that spontaneous reporting remained the most important source of drug
      withdrawals between 2005 and 2011. However, its relative importance decreased in
      comparison with that in 1997-2004. The importance of pharmacoepidemiological
      methods slightly increased but remained low. Finally, regulatory authorities seem
      to have more frequently based their safety decisions on multiple sources of
      evidence than before.

PMID- 22961934
TI  - Controllably tuning excited-state energy in ternary hosts for ultralow-voltage
      driven blue electrophosphorescence.

PMID- 22961935
TI  - Comparative analysis of photocaged RGDS peptides for cell patterning.
AB  - Photocaged RGDS is a cell nonadhesive tetrapeptide that can be activated with
      light to become cell-adhesive. Such molecules can find useful applications in
      controlling cell adhesion for biological study, drug development, and in forming
      dynamic, adhesion-controlled biomaterials. Herein, we prepared RGDS peptide
      photocaged either on the Arg-Gly backbone amide nitrogen atom (R[-]GDS) or Asp
      side chain carboxyl (RG[D]S). A critical comparison of the peptides' chemical and
      physiological properties relevant for biological applications was carried out. It
      was observed that RG[D]S was synthesized more readily via automated solid-phase
      synthesis, underwent uncaging with a rate constant 3-fold higher than R[-]GDS,
      and was more stable in aqueous solution. Automated docking studies were performed
      to examine the interactions of various caged RGDS peptides with cell surface
      integrin receptor to identify suitable locations for the photosensitive 2
      nitrobenzyl (NB) group for biological applications. A competitive binding ELISA
      method compared the ability of various peptides to bind to alpha(V)beta(3) cell
      integrin receptors and the data were found to be consistent with the modeling
      predictions. Finally, the application of our caged RGDS peptides in controlling
      cell adhesion to form cell patterns on a hydrogel material was presented.

PMID- 22961936
TI  - Robust REML estimation for k-component Poisson mixture with random effects:
      application to the epilepsy seizure count data and urinary tract infections data.
AB  - A robust version of residual maximum likelihood estimation for Poisson log-linear
      mixed model is developed, and the method is extended to k-component Poisson
      mixture with random effects. The method not only provides the robust estimators
      for the fixed effects and variance component parameters but also gives the robust
      prediction of random effects. Simulation results show that the proposed method is
      effective in limiting the impact of outliers under different data contamination
      schemes. The method is adopted to analyze the epilepsy seizure count data and the
      urinary tract infections data, which are deemed to contain several potential
      outliers. The results show that the proposed method provides better goodness of
      fit to the data and demonstrate the effect of the robust tuning mechanism.

PMID- 22961937
TI  - NMR studies of HAR1 RNA secondary structures reveal conformational dynamics in
      the human RNA.
AB  - Comparative genomics has shown that noncoding RNAs can display substantial
      differences between humans and chimpanzees. The human accelerated region 1 (HAR1)
      is a section in the human genome that exhibits the most strongly accelerated rate
      of nucleotide substitution in relation to the chimpanzee genome. It is associated
      with higher cognitive functions in human brains. The HAR1 region of the HAR1F
      gene is transcribed into a 118 nt noncoding RNA. We provide experimental data to
      validate available secondary structure models of chimpanzee and human HAR1 RNA by
      utilizing CD and NMR spectroscopy and applying a "divide-and-conquer" strategy.
      The mutations lead to more dynamic secondary and tertiary structure in the human
      HAR1 RNA, presumably as part of its function. We have also determined NMR
      solution structures of helix H1 as the most conserved part of the chimpanzee and
      human HAR1 RNAs. Helix H1 contains a GAA asymmetric internal loop, the structure
      of which had not been solved previously. 37 nt chimpanzee and human RNA fragments
      (c37 and h37 RNAs) differ in a single base pair. h37 RNA folds into a slightly
      more stable and rigid structure than c37 RNA. Both NMR structures show structural
      heterogeneity of the residues corresponding to the GAA loop.

PMID- 22961938
TI  - Hepatitis C virus core protein stimulates fibrogenesis in hepatic stellate cells
      involving the obese receptor.
AB  - Hepatitis C virus core protein (HCVcp), which is secreted by infected cells, is
      reported as an immunomodulator in immune cells. However, the effects of HCVcp on
      hepatic stellate cells (HSCs), the key cells in liver fibrosis, still remain
      unclear. In this study, we investigated the effects of HCVcp on obese receptor
      (ObR) related downstream signaling pathways and fibrogenic gene expression in
      HSCs. LX-2, a human HSC line, was incubated with HCVcp. Inhibitors and short
      interfering RNAs were used to interrogate the mechanisms of HCVcp action on HSCs.
      HCVcp (20-100 ng/ml) concentration-dependently stimulated alpha-smooth muscle
      actin (alpha-SMA) protein expression and mRNA expression of alpha-SMA,
      procollagen alpha2(I) and TGF-beta1 genes, with a plateau of 220% of controls at
      100 ng/ml. HCVcp induced mRNA and protein expression of ObR. Blocking of Ob-Rb
      with a neutralizing antibody inhibited phosphorylation of signal transducer and
      activator of transcription 3 (STAT3) and AMPKalpha stimulated by HCVcp.
      Furthermore, knockdown of Ob-Rb down-regulated HCVcp-induced STAT3, AKT, and
      AMPKalpha phosphorylation, and reversed HCVcp-suppressed mRNA expression of
      matrix metalloproteinase (MMP)-1, peroxisome proliferator-activated receptor
      (PPAR)gamma and sterol regulatory element binding protein-1c (SREBP-1c) genes.
      AMPKalpha signaling blockade reversed HCVcp-suppressed SREBP-1c mRNA expression.
      HCVcp stimulated reactive oxygen species formation and gp91(phox) (a component of
      NADPH oxidase) protein expression, together with AKT phosphorylation, leading to
      suppression of PPARgamma and SREBP-1c genes. Our results provide a new finding
      that HCVcp induced ObR-dependent Janus Kinase (JAK) 2-STAT3, AMPKalpha, and AKT
      signaling pathways and modulated downstream fibrogenetic gene expression in HSCs.

PMID- 22961939
TI  - Iodine-doped-poly(3,4-ethylenedioxythiophene)-modified Si nanowire 1D core-shell
      arrays as an efficient photocatalyst for solar hydrogen generation.
AB  - A new 1D core-shell strategy is demonstrated for a hydrogen-generation photo
      electrochemical cell (PEC). This Si/iodine-doped poly(3,4-ethylenedioxythiophene)
      (PEDOT) 1D nanocable array shows an encouraging solar-to-chemical energy
      conversion efficiency. Coating with iodine-doped PEDOT can effectively enhance
      the photocatalytic efficiency and stability of SiNW arrays. The PEC model
      proposed shows a potentially promising structure for H(2)  production using solar
      energy.

PMID- 22961940
TI  - Hepatic and abdominal carbon dioxide measurements detect and distinguish hepatic
      artery occlusion and portal vein occlusion in pigs.
AB  - Hepatic artery (HA) occlusion and portal vein (PV) occlusion are the most common
      vascular complications after liver transplantation with an impact on mortality
      and retransplantation rates. The detection of severe hypoperfusion may be delayed
      with currently available diagnostic tools. Hypoperfusion and anaerobically
      produced lactic acid lead to increases in tissue carbon dioxide. We investigated
      whether the continuous assessment of the intrahepatic and intra-abdominal partial
      pressure of carbon dioxide (PCO(2) ) could be used to detect and distinguish HA
      and PV occlusions in real time. In 13 pigs, the HA and the PV were fully occluded
      (n = 7) or gradually occluded (n = 6). PCO(2) was monitored intrahepatically and
      between loops of small intestine. The hepatic and intestinal metabolism was
      assessed with microdialysis and PV as well as hepatic vein blood samples, and the
      results were compared to clinical parameters for the systemic circulation and
      blood gas analysis. Total HA occlusion led to significant increases in hepatic
      PCO(2) and lactate, and this was accompanied by significant decreases in the
      partial pressure of oxygen and glucose. PV occlusion induced a significant
      increase in intestinal PCO(2) (but not hepatic PCO(2) ) along with significant
      increases in intestinal lactate and glycerol. Gradual HA occlusion and PV
      occlusion caused steady hepatic and intestinal PCO(2) increases, respectively.
      Systemic clinical parameters such as the blood pressure, heart rate, and cardiac
      output were affected only by PV occlusion. In conclusion, even gradual HA
      occlusion affects liver metabolism and can be reliably identified with hepatic
      PCO(2) measurements. Intestinal PCO(2) increases only during PV occlusion. A
      combination of hepatic and intestinal PCO(2) measurements can reliably diagnose
      the affected vessel and depict the severity of the occlusion, and this may emerge
      as a potential real-time clinical monitoring tool for the postoperative course of
      liver transplantation and enable early interventions.

PMID- 22961941
TI  - Protonation of an oxo-bridged diiron unit gives two different iron centers:
      synthesis and structure of a new class of diiron(III)-MU-hydroxo bisporphyrins
      and the control of spin states by using counterions.
AB  - Reported herein is a hitherto unknown family of diiron(III)-MU-hydroxo
      bisporphyrins in which two different spin states of Fe are stabilized in a single
      molecular framework, although both cores have identical molecular structures.
      Protonation of the oxo-bridged dimer (2) by using strong Bronsted acids, such as
      HI, HBF(4), and HClO(4), produce red MU-hydroxo complexes with I(3)(-) (3),
      BF(4)(-) (4), and ClO(4)(-) (5) counterions, respectively. The X-ray structure of
      the molecule reveals that the Fe-O bond length increases on going from the MU-oxo
      to the hydroxo complex, whereas the Fe-O(H)-Fe unit becomes more bent, which
      results in the smallest known Fe-O(H)-Fe angles of 142.5(2) and 141.2(1) degrees 
      for 3 and 5, respectively. In contrast, the Fe-O(H)-Fe angle remains unaltered in
      4 from the corresponding MU-oxo complex. The close approach of two rings in a
      molecule results in unequal core deformations in 3 and 4, whereas the cores are
      deformed almost equally but to a lesser extent in 5. Although 3 was found to have
      nearly high-spin and admixed intermediate Fe spin states in cores I and II,
      respectively, two admixed intermediate spin states were observed in 4. Even
      though the cores have identical chemical structures, crucial bond parameters,
      such as the Fe-N(p), Fe-O, and Fe???Ct(p) bond lengths and the ring deformations,
      are all different between the two Fe(III) centers in 3 and 4, which leads to an
      eventual stabilization of two different spin states of Fe in each molecule. In
      contrast, the two Fe centers in 5 are equivalent and assigned to high and
      intermediate spin states in the solid and solution states, respectively. The spin
      states are thus found to be dependent on the counterions and can also be
      reversibly interconverted. Upon protonation, the strong antiferromagnetic
      coupling in the MU-oxo dimer (J, -126.6 cm(-1)) is attenuated to almost zero in
      the MU-hydroxo complex with the I(3)(-) counterion, whereas the values of J are 
      36 and -42 cm(-1), respectively, for complexes with BF(4)(-) and ClO(4)(-)
      counterions.

PMID- 22961942
TI  - Colorimetric detection of mercury ions based on plasmonic nanoparticles.
AB  - The development of rapid, specific, cost-effective, and robust tools in
      monitoring Hg(2+) levels in both environmental and biological samples is of
      utmost importance due to the severe mercury toxicity to humans. A number of
      techniques exist, but the colorimetric assay, which is reviewed herein, is shown
      to be a possible tool in monitoring the level of mercury. These assays allow
      transforming target sensing events into color changes, which have applicable
      potential for in-the-field application through naked-eye detection. Specifically,
      plasmonic nanoparticle-based colorimetric assay exhibits a much better propensity
      for identifying various targets in terms of sensitivity, solubility, and
      stability compared to commonly used organic chromophores. In this review, recent
      progress in the development of gold nanoparticle-based colorimetric assays for
      Hg(2+) is summarized, with a particular emphasis on examples of functionalized
      gold nanoparticle systems with oligonucleotides, oligopeptides, and functional
      molecules. Besides highlighting the current design principle for plasmonic
      nanoparticle-based colorimetric probes, the discussions on challenges and the
      prospect of next-generation probes for in-the-field applications are also
      presented.

PMID- 22961944
TI  - Connecting with different audiences: the anatomy of communication is essential.
AB  - In the twenty-first century, communication has become truly global. Advances in
      technology have opened up a host of ways in which we are able to communicate to
      retrieve or pass on information and knowledge. In many cases we have moved from a
      place-based communication approach to one of increasing mobility. With this shift
      in approach, it is apparent that effective communication skills are perhaps even
      more important so that we can connect appropriately with diverse audiences.
      Despite this, relatively little attention has been paid to training our students
      in different modes of communication and therefore we may not be fully preparing
      our students to play their part in the global community. Given anatomy's place
      within many health-care curricula, an ideal avenue is available for anatomists to
      take the lead in providing communications skills training for students. There are
      a variety of approaches, some of which are outlined in this article, which can be
      used to create appropriate opportunities for developing different communication
      skills and these can be woven into existing practices to ensure courses do not
      become overburdened. A sustained approach to communication skills training will
      help equip our students to communicate easily with the many aspects of modern
      society.

PMID- 22961943
TI  - Embodied learning across the life span.
AB  - Developmental psychologists have long recognized the extraordinary influence of
      action on learning (Held & Hein, 1963; Piaget, 1952). Action experiences begin to
      shape our perception of the world during infancy (e.g., as infants gain an
      understanding of others' goal-directed actions; Woodward, 2009) and these effects
      persist into adulthood (e.g., as adults learn about complex concepts in the
      physical sciences; Kontra, Lyons, Fischer, & Beilock, 2012). Theories of embodied
      cognition provide a structure within which we can investigate the mechanisms
      underlying action's impact on thinking and reasoning. We argue that theories of
      embodiment can shed light on the role of action experience in early learning
      contexts, and further that these theories hold promise for using action to
      scaffold learning in more formal educational settings later in development.

PMID- 22961945
TI  - Presentation, management, and outcomes of 25 748 acute coronary syndrome
      admissions in Kerala, India: results from the Kerala ACS Registry.
AB  - AIMS: There are limited contemporary data on the presentation, management, and
      outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to
      develop a prospective registry to address treatment and health systems gaps in
      the management of ACSs in Kerala, India. METHODS AND RESULTS: We prospectively
      collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125
      hospitals in Kerala. We evaluated data on presentation, management, and in
      hospital mortality and major adverse cardiovascular events (MACE). We created
      random-effects multivariate regression models to evaluate predictors of outcomes
      while accounting for confounders. Mean (SD) age at presentation was 60 (12) years
      and did not differ among ACS types [ST-segment myocardial infarction (STEMI) =
      37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was
      high (>90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11%
      of unstable angina admissions. Percutaneous coronary intervention rates were
      marginally higher in STEMI admissions. Discharge medication rates were variable
      and generally suboptimal (<80%). In-hospital mortality and MACE rates were
      highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI
      diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06
      (2.36, 7.00)], symptom-to-door time >6 h [OR = 2.29 (1.73, 3.02)], and
      inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with
      higher risk of in-hospital mortality and door-to-needle time <30 min [OR = 0.44
      (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for
      risk of MACE. CONCLUSION: These data represent the largest ACS registry in India
      and demonstrate opportunities for improving ACS care.

PMID- 22961946
TI  - Pulmonary embolism: risk assessment and management.
AB  - Acute pulmonary embolism (PE) poses a significant burden on health and survival.
      Its severity ranges from asymptomatic, incidentally discovered subsegmental
      thrombi to massive, pressor-dependent PE complicated by cardiogenic shock and
      multisystem organ failure. Rapid and accurate risk stratification is therefore of
      paramount importance to ensure the highest quality of care. This article
      critically reviews currently available and emerging tools for risk-stratifying
      acute PE, and particularly for distinguishing between elevated (intermediate) and
      low risk among normotensive patients. We focus on the potential value of risk
      assessment strategies for optimizing severity-adjusted management. Apart from
      reviewing the current evidence on advanced early therapy of acute PE
      (thrombolysis, surgery, catheter interventions, vena cava filters), we discuss
      recent advances in oral anticoagulation with vitamin K antagonists, and with new
      direct inhibitors of factor Xa and thrombin, which may contribute to profound
      changes in the treatment and secondary prophylaxis of venous thrombo-embolism in
      the near future.

PMID- 22961947
TI  - Genome mining of the biosynthetic gene cluster of the polyene macrolide
      antibiotic tetramycin and characterization of a P450 monooxygenase involved in
      the hydroxylation of the tetramycin B polyol segment.
AB  - A polyene macrolide antibiotic tetramycin biosynthetic gene cluster was
      identified by genome mining and isolated from Streptomyces hygrospinosus var.
      beijingensis. Genetic and in silico analyses gave insights into the mechanism of
      biosynthesis of tetramycin, and a model of the tetramycin biosynthetic pathway is
      proposed. Inactivation of a cytochrome P450 monooxygenase gene, tetrK, resulted
      in the production of a tetramycin B precursor: tetramycin A, which lacks a
      hydroxy group in its polyol region. TetrK was subsequently overexpressed
      heterologously in E. coli with a His(6)  tag, and purified TetrK efficiently
      hydroxylated tetramycin A to afford tetramycin B. Kinetic studies revealed no
      inhibition of TetrK by substrate or product. Surprisingly, sequence-alignment
      analysis showed that TetrK, as a hydroxylase, has much higher homology with
      epoxidase PimD than with hydroxylases NysL and AmphL. The 3D structure of TetrK
      was then constructed by homology modeling with PimD as reference. Although TetrK
      and PimD catalyzed different chemical reactions, homology modeling indicated that
      they might share the same catalytic sites, despite also possessing some different
      sites correlated with substrate binding and substrate specificity. These findings
      offer good prospects for the production of improved antifungal polyene analogues.

PMID- 22961948
TI  - Early stages of oriented attachment: formation of twin ZnO nanorods under
      microwave irradiation.

PMID- 22961949
TI  - Deceased donation in Asia: challenges and opportunities.
AB  - KEY POINTS: 1. The deceased donation rate is low in Asia, and there is a critical
      shortage of liver grafts. 2. The number of liver transplants in Asia has
      increased rapidly during the last decade, mainly because of the rapid increase in
      the use of living donor liver transplantation (LDLT). 3. Various social,
      cultural, religious, and economic factors account for the low rate of deceased
      donation, and there is marked diversity between different countries and even
      within individual countries. 4. There are excellent opportunities for the
      actualization of deceased donation through legislation, education, donor actions,
      and innovations. 5. In the foreseeable future, LDLT will continue to play a
      crucial role for patients with liver disease in Asia.

PMID- 22961950
TI  - Explaining embodied cognition results.
AB  - From the late 1950s until 1975, cognition was understood mainly as disembodied
      symbol manipulation in cognitive psychology, linguistics, artificial
      intelligence, and the nascent field of Cognitive Science. The idea of embodied
      cognition entered the field of Cognitive Linguistics at its beginning in 1975.
      Since then, cognitive linguists, working with neuroscientists, computer
      scientists, and experimental psychologists, have been developing a neural theory
      of thought and language (NTTL). Central to NTTL are the following ideas: (a) we
      think with our brains, that is, thought is physical and is carried out by
      functional neural circuitry; (b) what makes thought meaningful are the ways those
      neural circuits are connected to the body and characterize embodied experience;
      (c) so-called abstract ideas are embodied in this way as well, as is language.
      Experimental results in embodied cognition are seen not only as confirming NTTL
      but also explained via NTTL, mostly via the neural theory of conceptual metaphor.
      Left behind more than three decades ago is the old idea that cognition uses the
      abstract manipulation of disembodied symbols that are meaningless in themselves
      but that somehow constitute internal "representations of external reality"
      without serious mediation by the body and brain. This article uniquely explains
      the connections between embodied cognition results since that time and results
      from cognitive linguistics, experimental psychology, computational modeling, and
      neuroscience.

PMID- 22961951
TI  - Multiphase designer droplets for liquid-liquid extraction.
AB  - Multiphase liquid droplets consisting of three connected but immiscible liquid
      phases are demonstrated. The droplets have designer geometries stabilized by
      surface energy patterns; aqueous phases prefer contact with hydrophilic surface
      while organic phases prefer contact with hydrophobic areas. The multiphase
      droplets are applied for liquid-liquid-liquid extraction.

PMID- 22961952
TI  - Practicable confidence intervals for current status data.
AB  - Although confidence intervals (CIs) for binary isotonic regression and current
      status survival data have been well studied theoretically, their practical
      application has been limited, in part because of poor performance in small
      samples and in part because of computational difficulties. Ghosh, Banerjee, and
      Biswas (2008, Biometrics 64, 1009-1017) described three approaches to
      constructing CIs: (i) the Wald-based method; (ii) the subsampling-based method;
      and (iii) the likelihood-ratio test (LRT)-based method. In simulation studies,
      they found that the subsampling-based method and LRT-based method tend to have
      better coverage probabilities than a simple Wald-based method that may perform
      poorly in realistic sample sizes. However, software implementing these approaches
      is currently unavailable. In this article, we show that by using transformations,
      simple Wald-based CIs can be improved with small and moderate sample sizes to
      have competitive performance with LRT-based method. Our simulations further show
      that a simple nonparametric bootstrap gives approximately correct CIs for the
      data generating mechanisms that we consider. We provide an R package that can be
      used to compute the Wald-type and the bootstrap CIs and demonstrate its practical
      utility with two real data analyses.

PMID- 22961953
TI  - Curriculum integration = course disintegration: what does this mean for anatomy?
AB  - Many basic scientists including anatomists are currently involved in decisions
      related to revisions of the undergraduate medical curriculum. Integration is a
      common theme in many of these decisions. As described by Harden, integration can
      occur along a multistep continuum from independent, discipline-based courses to a
      completely interdisciplinary curriculum. For anatomy, each derivative of
      curricular integration can be shown to involve progressive disruptions of the
      temporal and topographical relationship between organ systems in a body region,
      of the temporal relationship with other courses in a harmonized curriculum, and
      of the relationships between components of organ systems when integration is
      implemented in thematic curricula. Drawing from our experience teaching in
      various types of integrated medical curricula, we encourage readers to proceed
      cautiously with their curricular decisions because each one can have gains and
      losses that may impact learning in the new format.

PMID- 22961954
TI  - In vitro and in vivo studies of rhBMP2-coated PS/PCL fibrous scaffolds for bone
      regeneration.
AB  - The control of porous microstructure and the use of rhBMP2 as surface coating on
      bone substitutes have been recognized as key factors to accelerate
      osteoconductivity. In this study, instead of using a meso-porous fibrous scaffold
      of poly-epsilon-caprolactone (PCL), a micro- and macro-porous fibrous scaffold,
      made up of blended polystyrene (PS) and PCL, was created to investigate these key
      factors. In vitro studies, MTT assay and scanning electron microscope (SEM)
      morphology confirmed that PS/PCL fibrous membrane has non-toxicity and shows
      excellent cells adhesion and proliferation behavior. Significant improvements
      regarding cell attachment, cell growth, and cell proliferation were observed
      using recombinant human bone morphogenetic protein-2 (rhBMP2)-coated PS/PCL
      fibrous scaffold confirmed by SEM and confocal observation. Results of micro-CT
      scanning and the Hematoxylin & Eosin/Masson's Trichrom staining of tissue
      sections from the post-implantation revealed that rhBMP2-coated PS/PCL fibrous
      scaffold recovered over 75 vol % of the bone defect after 8 weeks of
      implantation.

PMID- 22961955
TI  - Design of a 13C magnetic resonance probe using a deuterated methoxy group as a
      long-lived hyperpolarization unit.

PMID- 22961956
TI  - Truly inefficient or providing better quality of care? Analysing the relationship
      between risk-adjusted hospital costs and patients' health outcomes.
AB  - Observed variation in hospital costs may be attributable to differences in
      patients' health outcomes. Previous studies have resorted to inherently
      incomplete outcome measures such as mortality or re-admission rates to assess
      this claim. This study makes use of a novel dataset of routinely collected
      patient-reported outcome measures (PROMs) linked to inpatient records to (i)
      access the degree to which cost variation is associated with variation in
      patients' health gain and (ii) explore how far judgement about hospital cost
      performance changes when health outcomes are accounted for. We use multilevel
      modelling to address the clustering of patients in providers and isolate
      unexplained cost variation. We find some evidence of a U-shaped relationship
      between risk-adjusted costs and outcomes for hip replacement surgery. For three
      other procedures (knee replacement, varicose vein and groin hernia surgery), the
      estimated relationship is sensitive to the choice of PROM instrument. We do not
      observe substantial changes in cost performance estimates when outcomes are
      explicitly accounted for.

PMID- 22961957
TI  - Silicon nanowire charge-trap memory incorporating self-assembled iron oxide
      quantum dots.
AB  - Charge-trap non-volatile memory devices based upon the precise integration of
      quantum dot storage elements with silicon nanowire field-effect transistors are
      described. Template-assisted assembly yields an ordered array of FeO QDs within
      the trenches that separate highly aligned SiNWs, and injected charges are
      reversibly stored via Fowler-Nordheim tunneling into the QDs. Stored charges
      shift the transistor threshold voltages, providing the basis for a memory device.
      Quantum dot size is found to strongly influence memory performance metrics. 

PMID- 22961958
TI  - Mitraclip therapy and surgical mitral repair in patients with moderate to severe
      left ventricular failure causing functional mitral regurgitation: a single-centre
      experience.
AB  - OBJECTIVES: Surgical mitral repair is the conventional treatment for severe
      symptomatic functional mitral regurgitation (FMR). Mitraclip therapy is an
      emerging option for selected high-risk patients with FMR. The aim of this study
      was to report the outcomes of patients who underwent a surgical mitral repair and
      Mitraclip therapy for FMR in our experience. METHODS: From March 2000 and April
      2011, 143 patients with FMR were treated in our institution: 91 patients (63.6%)
      underwent surgical mitral repair (49% ischaemic; 51% idiopathic) and 52 (36.4%)
      underwent Mitraclip implantation (71% ischaemic; 29% idiopathic). Associated
      procedures in the surgical group were myocardial revascularization in 35%,
      tricuspid repair in 25% and atrial fibrillation ablation in 26%. Follow-up was
      100% complete (median 18; 6.4-45 months for surgery and 8.5; 4-12 months for
      Mitraclip). RESULTS: Mitraclip patients were older (P = 0.04), had higher log
      EuroSCORE (P < 0.0001), lower LVEF (P = 0.006) and higher left ventricular
      diameter (P = 0.01 for left ventricular end-diastolic diameter and P = 0.05 for
      left ventricular end-systolic diameter). Major postoperative infection or sepsis
      occurrence was higher in the surgical group (16.3 vs. 3.8%; P = 0.01), while no
      differences were observed in terms of acute renal failure, cardiogenic shock,
      cerebrovascular accident and acute myocardial infarction. Length-of-stay was 11
      days (IQR: 7-19 days) for surgery and 5 days (IQR: 4-9 days) for MitraClip (P <
      0.0001). In-hospital mortality was 6.6% for surgery (6/91) and 0% for Mitraclip
      (P = 0.01). Surgery was identified as a predictor of in-hospital death (OR: 2.61;
      P = 0.01). Residual MR >= 3+ at discharge was 0% for surgery and 9.6% for
      Mitraclip (P = 0.002). At follow-up, actuarial survival at 1 year was 88.9 +/-
      3.5% for surgery and 87.5 +/- 7% for Mitraclip (P = 0.6). Actuarial freedom from
      MR >= 3+ at 1 year was 79.1 +/- 8% for MitraClip and 94 +/- 2% for surgery (P =
      0.01). At last follow-up, most of the survivors were in NYHA class I-II.
      CONCLUSIONS: Mitraclip therapy is a safe therapeutic option in selected high-risk
      patients with FMR, and it is associated with a lower hospital mortality and
      shorter length-of-stay compared with surgery, in spite of worse preoperative
      conditions. Early and 1-year rates of recurrent MR are higher with Mitraclip.
      Further studies are needed to determine the long-term clinical impact.

PMID- 22961959
TI  - Controlling the assembly of chalcogenide anions in ionic liquids: from binary
      Ge/Se through ternary Ge/Sn/Se to binary Sn/Se frameworks.
AB  - Seven compounds with binary or ternary Ge/Se, Ge/Sn/Se, or Sn/Se anionic
      substructures crystallized upon the ionothermal reactions of
      [K(4)(H(2)O)(3)][Ge(4)Se(10)] with SnCl(4).5H(2)O or SnCl(2) in [BMMIm][BF(4)] or
      [BMIm][BF(4)] (BMMIm=1-butyl-2,3-dimethyl-imidazolium, BMIm=1-butyl-3-methyl
      imidazolium). The products were obtained by subtly varying the reaction
      conditions; the nature and amount of an additional amine was the most important
      parameter in the product selection and in determining the Sn/Ge ratio in the
      isolated products. The crystal structures of these chalcogenides were based on
      complex anions with unprecedented topologies that varied from discrete clusters
      (0D) through 1D chain structures or 2D layers to 3D frameworks. The architecture
      and composition of the title compounds were well reflected by their optical
      absorption behavior. Herein, we report a convenient approach for the generation
      of chalcogenidometallate phases with fine-tunable electronic properties in ionic
      liquids, which have been inaccessible by traditional methods.

PMID- 22961960
TI  - Antegrade flow across incomplete vessel occlusions can be distinguished from
      retrograde collateral flow using 4-dimensional computed tomographic angiography.
AB  - BACKGROUND AND PURPOSE: In acute stroke patients with intracranial vessel
      occlusion, angiographic demonstration of antegrade contrast opacification distal
      to the occlusion site (termed the "clot outline sign") has been associated with
      higher rates of vessel recanalization. We sought to determine whether antegrade
      flow can be demonstrated on time-resolved 4-dimensional computed tomographic
      angiography (4-dimensional CTA), whether it can be distinguished from retrograde
      collateral flow, and if it can be used to predict early recanalization. METHODS:
      Fifty-seven acute stroke patients with intracranial anterior circulation vessel
      occlusion were retrospectively identified. All patients had received a multimodal
      computed tomography examination including thin-section 4-dimensional CTA and
      subsequent digital subtraction angiography as part of an endovascular procedure.
      Pretreatment 4-dimensional CTA and single-phase CTA were assessed for presence of
      antegrade contrast opacification distal to the occlusion site. Digital
      subtraction angiograms were reviewed for preintervention Thrombolysis in Cerebral
      Infarction grade, presence of the clot outline sign, as well as postintervention
      Thrombolysis in Cerebral Infarction grade. RESULTS: On 4-dimensional CTA,
      evidence of antegrade flow was present in 11 of 57 cases (19.3%). Compared with
      angiography, 4-dimensional CTA predicted antegrade flow with 100% sensitivity and
      97.9% specificity. Single-phase CTA offered 40% sensitivity and 87.2%
      specificity. Early recanalization occurred in 3 patients (6.5%) after intravenous
      thrombolysis (n=46); all demonstrated antegrade flow on 4-dimensional CTA.
      CONCLUSIONS: Using 4-dimensional CTA, it is possible to noninvasively distinguish
      antegrade flow across a cerebral artery occlusion from retrograde collateral
      flow. Presence of antegrade flow on 4-dimensional CTA is associated with an
      increased chance of early vessel recanalization.

PMID- 22961962
TI  - Serious cardiac arrhythmias after stroke: incidence, time course, and predictors-
      a systematic, prospective analysis.
AB  - BACKGROUND AND PURPOSE: Patients with acute cerebrovascular events are
      susceptible to serious cardiac arrhythmias, but data on the time course and the
      determinants of their onset are scarce. METHODS: The prospective Stroke
      Arrhythmia-Monitoring-Database (SAMBA) assessed cardiac arrhythmias with need for
      urgent evaluation and treatment in 501 acute neurovascular patients during the
      first 72 hours after admission to a monitored stroke unit. Arrhythmias were
      systematically detected by structured processing of telemetric data. Time of
      arrhythmia onset and predisposing factors were investigated. RESULTS: Significant
      cardiac arrhythmias occurred in 25.1% of all patients. Incidence was highest
      during the first 24 hours after admission. Serious arrhythmic tachycardia
      (ventricular or supraventricular>130 beats/min) was more frequent than
      bradycardic arrhythmia (sinus-node dysfunction, bradyarrhythmia, or
      atrioventricular block  degrees II and  degrees III). Arrhythmias were
      independently associated with higher age and severer neurological deficits as
      measured by the National Institutes of Health Stroke Scale on admission.
      CONCLUSIONS: The risk for significant cardiac arrhythmia after an acute
      cerebrovascular event is highest during the first 24 hours of care and declines
      with time during the first 3 days. Along with established vascular risk factors,
      the National Institutes of Health Stroke Scale may be considered for a stratified
      allocation of monitoring capabilities. CLINICAL TRIAL REGISTRATION: URL:
      www.clinicaltrials.gov. Unique identifier: NCT01177748.

PMID- 22961961
TI  - Genome-wide association study of intracranial aneurysms confirms role of Anril
      and SOX17 in disease risk.
AB  - BACKGROUND: Genomewide association studies have identified novel genetic factors
      that contribute to intracranial aneurysm (IA) susceptibility. We sought to
      confirm previously reported loci, to identify novel risk factors, and to evaluate
      the contribution of these factors to familial and sporadic IA. METHOD: We
      utilized 2 complementary samples, one recruited on the basis of a dense family
      history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other
      without regard to family history (discovery sample 2: 1095 IA cases and 1286
      controls). Imputation was used to generate a common set of single nucleotide
      polymorphisms (SNP) across samples, and a logistic regression model was used to
      test for association in each sample. Results from each sample were then combined
      in a metaanalysis. RESULTS: There was only modest overlap in the association
      results obtained in the 2 samples. In neither sample did results reach genomewide
      significance. However, the metaanalysis yielded genomewide significance for SNP
      on chromosome 9p (CDKN2BAS; rs6475606; P=3.6*10(-8)) and provided further
      evidence to support the previously reported association of IA with SNP in SOX17
      on chromosome 8q (rs1072737; P=8.7*10(-5)). Analyses suggest that the effect of
      smoking acts multiplicatively with the SNP genotype, and smoking has a greater
      effect on risk than SNP genotype. CONCLUSIONS: In addition to replicating several
      previously reported loci, we provide further evidence that the association on
      chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an
      antisense noncoding RNA).

PMID- 22961963
TI  - Lipoprotein phospholipase A2 and cerebral microbleeds in the Framingham Heart
      Study.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) attributable to cerebral
      amyloid angiopathy generally occur in lobar regions, whereas those attributable
      to hypertensive vasculopathy are deep. Inflammation may be an underlying
      mechanism for CMB, with varying associations according to CMB location.
      Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular
      inflammation associated with risk of ischemic stroke and dementia. We
      hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of
      CMB, with possible regional specificity. METHODS: Framingham Offspring
      participants aged 65 years or older with available Lp-PLA2 measures and brain
      magnetic resonance imaging were included. Logistic regression models were used to
      relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex,
      medication use (aspirin, anticoagulants, and statins), systolic blood pressure,
      APOE, current smoking, and diabetes. RESULTS: Eight-hundred nineteen participants
      (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were
      lobar, and 27 (3%) were deep. We did not observe significant associations of CMB
      and LpPLA2 measures in multivariable adjusted analyses. However, there was a
      significant interaction between APOE genotype and Lp-PLA2 activity in their
      relation to presence of deep CMB (P interaction=0.01). Among persons with APOE
      epsilon3/epsilon3, the odds ratio for deep CMB was 0.95 (confidence interval,
      0.59-1.53; P=0.83), whereas among those with at least 1 epsilon2 or epsilon4
      allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006).
      CONCLUSIONS: In our community-based sample of older adults, there was no
      significant association of Lp-PLA2 with total or lobar CMB. The association of
      higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE
      epsilon2 or epsilon4 allele merits replication.

PMID- 22961964
TI  - Features of acute ischemic stroke with rheumatic heart disease in a hospitalized
      Chinese population.
AB  - BACKGROUND AND PURPOSE: Rheumatic heart disease (RHD) is an important risk factor
      for ischemic stroke in developing countries. Observational data on its
      characteristics and influence on outcome or recurrence of ischemic stroke are
      scarce. We aimed to investigate proportions, characteristics, functional outcome,
      and recurrence of acute ischemic stroke patients with RHD in a hospitalized
      Chinese population. METHODS: We prospectively enrolled consecutive patients with
      acute ischemic stroke who were admitted within 1 month of stroke onset from
      January 2003 to February 2007, into the analysis. Clinical characteristics such
      as age, gender, risk factors, and National Institutes of Health Stroke Scale on
      admission were investigated. Basic characteristics, functional outcomes, and
      recurrence were compared between RHD group and nonRHD group. RESULTS: Of the 1638
      cases included, RHD was present in 130 patients (7.9%). RHD patients, compared
      with those without RHD, were younger, more frequently female, and more often had
      experienced atrial fibrillation and higher National Institutes of Health Stroke
      Scale score on admission (all P<0.006). After adjustment for age, sex, and
      National Institutes of Health Stroke Scale on admission, the death risk in
      patients with RHD was 2.0-fold higher at 3 months, 6 months, and 1 year compared
      with patients without RHD (all P<0.013). Compared with patients without RHD,
      those with RHD showed a significantly higher cumulative recurrence rate (13.6% vs
      6.0%; P=0.001, log rank test) by 1-year cumulative recurrent curves. CONCLUSIONS:
      Stroke attributable to RHD is still common in the Chinese population. RHD was
      associated with 2-fold increased risk of death and 1-fold increased risk of
      recurrence in stroke patients.

PMID- 22961965
TI  - Pyran formation by an atypical CYP-mediated four-electron oxygenation-cyclization
      cascade in an engineered aureothin pathway.
AB  - Small changes, big effect: A new aureothin derivative, aureopyran, which features
      an unusual pyran backbone, was generated by simply altering the enzymatic
      methylation topology. The alpha-pyrone ring hampers the correct placement of the
      polyketide backbone in the multifunctional cytochrome P450 monooxygenase AurH.
      Instead of a tetrahydrofuran ring, an oxo intermediate is formed that readily
      undergoes a rare electrocyclization reaction.

PMID- 22961966
TI  - Editorial: Biotech reviews on plants, lignocellulose, sequencing, genome
      engineering and Aspergilli.
AB  - By reading this special issue on "Biotech Reviews" you will once again get an
      insight on the broadness of the field. Topics include plant biotechnology,
      lignocellulose conversion to platform chemicals, DNA sequencing, genome
      engineering of mammalian cells and industrial application of Aspergilli.

PMID- 22961971
TI  - Living donor liver transplantation using grafts with hepatic cysts.
AB  - Cystic lesions in the liver are often found through the evaluation of liver
      donors. Multiple cysts are worrisome, and donor candidates with multiple cysts
      may be unacceptable as liver donors, especially when their recipients have
      fibrocystic disease (FCD), which is an inherited disorder. This study reviewed
      183 cases of living donor liver transplantation. We collected clinical and
      radiological data associated with donors with cystic lesions and with donors
      without cystic lesions, and we evaluated the outcomes of these donors and their
      recipients. As part of the preoperative radiological assessment of grafts,
      magnetic resonance cholangiography (MRC) was performed to evaluate the biliary
      anatomy of donor candidates with multiple cysts. Thirty-four donors (18.6%) had 1
      or more cystic lesions in the liver, and 6 of these donors had multiple cysts
      (ie, >10). Donors with multiple cysts were older and heavier, and there was a
      significant relationship between these donors and recipients whose original
      disease was FCD. During the follow-up (median = 3.1 years), all donors with
      cystic lesions were found to be doing well without any major postoperative
      complications. Fifteen recipients who received grafts with cystic lesions (12
      left-sided lobes and 3 right-sided lobes) had no complications related to the
      cystic lesions. In conclusion, donors with cystic lesions may be acceptable as
      liver donors, although our data are limited mostly to left-sided lobe donation
      with a short follow-up period. MRC should be preoperatively performed to rule out
      any biliary anomalies, especially in donor candidates whose recipients have FCD.

PMID- 22961972
TI  - Organic vapor sensing based on the light scattering effect of condensed
      microdroplets.

PMID- 22961973
TI  - Structural alterations in chronic lymphocytic leukaemia. Cytogenetic and FISH
      analysis.
AB  - In this study, we described cytogenetics and fluorescence in situ hybridization
      (FISH) analysis performed in chronic lymphocytic leukaemia (CLL) patients with
      structural alterations. Results were correlated with clinical characteristics. A
      total of 38 CLL patients: 16 cases with complex and 22 with simple karyotypes
      were studied. For comparison of clinical parameters, a control group of 78 CLL
      patients with normal karyotype and without FISH genomic alterations were also
      evaluated. We found 38 structural abnormalities not previously described in the
      literature, 28 (74%) of them were translocations. In cases with complex
      karyotypes, chromosomes 6, 8 and 13 were the most frequently involved in new
      alterations (nine each), followed by chromosomes 12, 14 and 15 (six each).
      Chromosome 8p was particularly involved in losses, being 8p21-pter the commonest
      region of overlap. Cases with simple karyotypes, showed del(6q) as the most
      frequent alteration (39%). Del(9)(q11) was recurrent in our series. Analysis of
      clinical parameters showed significant differences in white blood count (p =
      0.005) and platelet count (p = 0.015) between patients with structural
      alterations and the control group. In addition, patients with structural
      alterations had a significantly shorter time to first treatment (TFT) (29 months)
      than the control group (69 months) (p = 0.037). Cases with complex karyotypes had
      a lower proportion of patients in Rai 0 clinical stage (15.4% vs 75%) (p = 0.005)
      and higher beta2 microglobulin levels (3.3 vs 2.5 ug/mL) (p = 0.037) than those
      with simple karyotypes. Furthermore, a shorter TFT (13 months) and overall
      survival (56 months) in the complex karyotypes group compared with controls (69
      and 144 months, respectively) (p = 0.015 and p = 0.005, respectively) were also
      found. Our results support the importance of cytogenetic analysis for clinical
      outcome in CLL and suggest that the diversity of genomic alterations is much
      greater than previously appreciated.

PMID- 22961974
TI  - Bacteria-responsive multifunctional nanogel for targeted antibiotic delivery.
AB  - Bacteria-Responsive Multifunctional Nanogel: We developed a bacteria-responsive
      multifunctional nanogel for targeted antibiotic delivery, in which bacterial
      enzymes are utilized to trigger antibiotic release by degrading the
      polyphosphoester core. The mannosylated nanogel preferentially delivers drugs to
      macrophages and leads to drug accumulation at bacterial infection sites through
      macrophage transport. This nanogel provides macrophage targeting and lesion site
      activatable drug release properties, which enhances bacterial growth inhibition.

PMID- 22961975
TI  - A novel suture-based method for efficient transplantation of stem cells.
AB  - Advances in regenerative medicine have improved the potential of using cellular
      therapy for treating several diseases. However, the effectiveness of new cellular
      therapies is largely limited by low cell engraftment and inadequate localization.
      To improve on these limitations, we developed a novel delivery mechanism using
      cell-seeded biological sutures. We demonstrate the ability of cell-seeded
      biological sutures to efficiently implant human mesenchymal stem cells (hMSCs) to
      specific regions within the beating heart; a tissue known to have low cell
      retention and engraftment shortly after delivery. Cell-seeded biological sutures
      were developed by bundling discrete microthreads extruded from extracellular
      matrix proteins, attaching a surgical needle to the bundle and seeding the bundle
      with hMSCs. During cell preparation, hMSCs were loaded with quantum dot
      nanoparticles for cell tracking within the myocardium. Each biological suture
      contained an average of 5903 +/- 1966 hMSCs/cm suture length. Delivery efficiency
      was evaluated by comparing cell-seeded biological suture implantation with
      intramyocardial (IM) cell injections (10,000 hMSCs in 35 MUL) into the left
      ventricle of normal, noninfarcted rat hearts after 1 h. Delivery efficiency of
      hMSCs by biological sutures (63.6 +/- 10.6%) was significantly higher than IM
      injection (11.8 +/- 6.2%; p < 0.05). Cell-tracking analysis indicated suture
      delivered hMSCs were found throughout the thickness of the ventricular
      myocardium: along the entire length of the biological suture track, localizing
      closely with native myocardium. These results suggest cell-seeded biological
      sutures can deliver cells to the heart more efficiently than conventional
      methods, demonstrating an effective delivery method for implanting cells in soft
      tissue.

PMID- 22961976
TI  - Societal views on NICE, cancer drugs fund and value-based pricing criteria for
      prioritising medicines: a cross-sectional survey of 4118 adults in Great Britain.
AB  - The criteria used by the National Institute for Health and Clinical Excellence
      (NICE) for accepting higher incremental cost-effectiveness ratios for some
      medicines over others, and the recent introduction of the Cancer Drugs Fund (CDF)
      in England, are assumed to reflect societal preferences for National Health
      Service resource allocation. Robust empirical evidence to this effect is lacking.
      To explore societal preferences for these and other criteria, including those
      proposed for rewarding new medicines under the future value-based pricing (VBP)
      system, we conducted a choice-based experiment in 4118 UK adults via web-based
      surveys. Preferences were determined by asking respondents to allocate fixed
      funds between different patient and disease types reflecting nine specific
      prioritisation criteria. Respondents supported the criteria proposed under the
      VBP system (for severe diseases, address unmet needs, are innovative--provided
      they offered substantial health benefits, and have wider societal benefits) but
      did not support the end-of-life premium or the prioritisation of children or
      disadvantaged populations as specified by NICE, nor the special funding status
      for treatments of rare diseases, nor the CDF. Policies introduced on the basis of
      perceived--and not actual--societal values may lead to inappropriate resource
      allocation decisions with the potential for significant population health and
      economic consequences.

PMID- 22961977
TI  - A perceptual-motor deficit predicts social and communicative impairments in
      individuals with autism spectrum disorders.
AB  - Individuals with autism spectrum disorders (ASDs) have known impairments in
      social and motor skills. Identifying putative underlying mechanisms of these
      impairments could lead to improved understanding of the etiology of core
      social/communicative deficits in ASDs, and identification of novel intervention
      targets. The ability to perceptually integrate one's physical capacities with
      one's environment (affordance perception) may be such a mechanism. This ability
      has been theorized to be impaired in ASDs, but this question has never been
      directly tested. Crucially, affordance perception has shown to be amenable to
      learning; thus, if it is implicated in deficits in ASDs, it may be a valuable
      unexplored intervention target. The present study compared affordance perception
      in adolescents and adults with ASDs to typically developing (TD) controls. Two
      groups of individuals (adolescents and adults) with ASDs and age-matched TD
      controls completed well-established action capability estimation tasks
      (reachability, graspability, and aperture passability). Their caregivers
      completed a measure of their lifetime social/communicative deficits. Compared
      with controls, individuals with ASDs showed unprecedented gross impairments in
      relating information about their bodies' action capabilities to visual
      information specifying the environment. The magnitude of these deficits strongly
      predicted the magnitude of social/communicative impairments in individuals with
      ASDs. Thus, social/communicative impairments in ASDs may derive, at least in
      part, from deficits in basic perceptual-motor processes (e.g. action capability
      estimation). Such deficits may impair the ability to maintain and calibrate the
      relationship between oneself and one's social and physical environments, and
      present fruitful, novel, and unexplored target for intervention.

PMID- 22961978
TI  - Near-infrared emitting radioactive gold nanoparticles with molecular
      pharmacokinetics.

PMID- 22961979
TI  - SMAD versus non-SMAD signaling is determined by lateral mobility of bone
      morphogenetic protein (BMP) receptors.
AB  - Bone (or body) morphogenetic proteins (BMPs) belong to the TGFbeta superfamily
      and are crucial for embryonic patterning and organogenesis as well as for adult
      tissue homeostasis and repair. Activation of BMP receptors by their ligands leads
      to induction of several signaling cascades. Using fluorescence recovery after
      photobleaching, FRET, and single particle tracking microscopy, we demonstrate
      that BMP receptor type I and II (BMPRI and BMPRII) have distinct lateral mobility
      properties within the plasma membrane, which is mandatory for their involvement
      in different signaling pathways. Before ligand binding, BMPRI and a subpopulation
      of BMPRII exhibit confined motion, reflecting preassembled heteromeric receptor
      complexes. A second free diffusing BMPRII population only becomes restricted
      after ligand addition. This paper visualizes time-resolved BMP receptor complex
      formation and demonstrates that the lateral mobility of BMPRI has a major impact
      in stabilizing heteromeric BMPRI-BMPRII receptor complexes to differentially
      stimulate SMAD versus non-SMAD signaling.

PMID- 22961980
TI  - Crystal structures of cholesteryl ester transfer protein in complex with
      inhibitors.
AB  - Human plasma cholesteryl ester transfer protein (CETP) transports cholesteryl
      ester from the antiatherogenic high-density lipoproteins (HDL) to the
      proatherogenic low-density and very low-density lipoproteins (LDL and VLDL).
      Inhibition of CETP has been shown to raise human plasma HDL cholesterol (HDL-C)
      levels and is potentially a novel approach for the prevention of cardiovascular
      diseases. Here, we report the crystal structures of CETP in complex with
      torcetrapib, a CETP inhibitor that has been tested in phase 3 clinical trials,
      and compound 2, an analog from a structurally distinct inhibitor series. In both
      crystal structures, the inhibitors are buried deeply within the protein, shifting
      the bound cholesteryl ester in the N-terminal pocket of the long hydrophobic
      tunnel and displacing the phospholipid from that pocket. The lipids in the C
      terminal pocket of the hydrophobic tunnel remain unchanged. The inhibitors are
      positioned near the narrowing neck of the hydrophobic tunnel of CETP and thus
      block the connection between the N- and C-terminal pockets. These structures
      illuminate the unusual inhibition mechanism of these compounds and support the
      tunnel mechanism for neutral lipid transfer by CETP. These highly lipophilic
      inhibitors bind mainly through extensive hydrophobic interactions with the
      protein and the shifted cholesteryl ester molecule. However, polar residues, such
      as Ser-230 and His-232, are also found in the inhibitor binding site. An enhanced
      understanding of the inhibitor binding site may provide opportunities to design
      novel CETP inhibitors possessing more drug-like physical properties, distinct
      modes of action, or alternative pharmacological profiles.

PMID- 22961981
TI  - Alternative splicing of a protein domain indispensable for function of transient
      receptor potential melastatin 3 (TRPM3) ion channels.
AB  - TRPM3 channels form ionotropic steroid receptors in the plasma membrane of
      pancreatic beta and dorsal root ganglion cells and link steroid hormone signaling
      to insulin release and pain perception, respectively. We identified and compared
      the function of a number of TRPM3 splice variants present in mouse, rat and human
      tissues. We found that variants lacking a region of 18 amino acid residues
      display neither Ca(2+) entry nor ionic currents when expressed alone. Hence,
      splicing removes a region that is indispensable for channel function, which is
      called the ICF region. TRPM3 variants devoid of this region (TRPM3DeltaICF), are
      ubiquitously present in different tissues and cell types where their transcripts
      constitute up to 15% of the TRPM3 isoforms. The ICF region is conserved
      throughout the TRPM family, and its presence in TRPM8 proteins is also necessary
      for function. Within the ICF region, 10 amino acid residues form a domain
      essential for the formation of operative TRPM3 channels. TRPM3DeltaICF variants
      showed reduced interaction with other TRPM3 isoforms, and their occurrence at the
      cell membrane was diminished. Correspondingly, coexpression of DeltaICF proteins
      with functional TRPM3 subunits not only reduced the number of channels but also
      impaired TRPM3-mediated Ca(2+) entry. We conclude that TRPM3DeltaICF variants are
      regulatory channel subunits fine-tuning TRPM3 channel activity.

PMID- 22961982
TI  - Crystal structure of Arabidopsis Deg2 protein reveals an internal PDZ ligand
      locking the hexameric resting state.
AB  - Eukaryotic organelles have developed elaborate protein quality control systems to
      ensure their normal activity, among which Deg/HtrA proteases play an essential
      role. Plant Deg2 protease is a homologue of prokaryotic DegQ/DegP proteases and
      is located in the chloroplast stroma, where its proteolytic activity is required
      to maintain the efficiency of photosynthetic machinery during stress. Here, we
      demonstrate that Deg2 exhibits dual protease-chaperone activities, and we present
      the hexameric structure of Deg2 complexed with co-purified peptides. The
      structure shows that Deg2 contains a unique second PDZ domain (PDZ2) following a
      conventional PDZ domain (PDZ1), with PDZ2 orchestrating the cage assembly of
      Deg2. We discovered a conserved internal ligand for PDZ2 that mediates hexamer
      formation and thus locks the protease in the resting state. These findings
      provide insight into the diverse modes of PDZ domain-mediated regulation of Deg
      proteases.

PMID- 22961983
TI  - Induction of cancerous stem cells during embryonic stem cell differentiation.
AB  - Stem cell maintenance depends on their surrounding microenvironment, and
      aberrancies in the environment have been associated with tumorigenesis. However,
      it remains to be elucidated whether an environmental aberrancy can act as a
      carcinogenic stress for cellular transformation of differentiating stem cells
      into cancer stem cells. Here, utilizing mouse embryonic stem cells as a model, it
      was illustrated that environmental aberrancy during differentiation leads to the
      emergence of pluripotent cells showing cancerous characteristics. Analogous to
      precancerous stages, DNA lesions were spontaneously accumulated during embryonic
      stem cell differentiation under aberrational environments, which activates
      barrier responses such as senescence and apoptosis. However, overwhelming such
      barrier responses, piled-up spheres were subsequently induced from the previously
      senescent cells. The sphere cells exhibit aneuploidy and dysfunction of the Arf
      p53 module as well as enhanced tumorigenicity and a strong self-renewal capacity,
      suggesting development of cancerous stem cells. Our current study suggests that
      stem cells differentiating in an aberrational environment are at risk of cellular
      transformation into malignant counterparts.

PMID- 22961984
TI  - A sequential mechanism for exosite-mediated factor IX activation by factor XIa.
AB  - During blood coagulation, the protease factor XIa (fXIa) activates factor IX
      (fIX). We describe a new mechanism for this process. FIX is cleaved initially
      after Arg(145) to form fIXalpha, and then after Arg(180) to form the protease
      fIXabeta. FIXalpha is released from fXIa, and must rebind for cleavage after
      Arg(180) to occur. Catalytic efficiency of cleavage after Arg(180) is 7-fold
      greater than for cleavage after Arg(145), limiting fIXalpha accumulation. FXIa
      contains four apple domains (A1-A4) and a catalytic domain. Exosite(s) on fXIa
      are required for fIX binding, however, there is lack of consensus on their
      location(s), with sites on the A2, A3, and catalytic domains described. Replacing
      the A3 domain with the prekallikrein A3 domain increases K(m) for fIX cleavage
      after Arg(145) and Arg(180) 25- and >= 90-fold, respectively, and markedly
      decreases k(cat) for cleavage after Arg(180). Similar results were obtained with
      the isolated fXIa catalytic domain, or fXIa in the absence of Ca(2+). Forms of
      fXIa lacking the A3 domain exhibit 15-fold lower catalytic efficiency for
      cleavage after Arg(180) than for cleavage after Arg(145), resulting in fIXalpha
      accumulation. Replacing the A2 domain does not affect fIX activation. The results
      demonstrate that fXIa activates fIX by an exosite- and Ca(2+)-mediated release
      rebind mechanism in which efficiency of the second cleavage is enhanced by
      conformational changes resulting from the first cleavage. Initial binding of fIX
      and fIXalpha requires an exosite on the fXIa A3 domain, but not the A2 or
      catalytic domain.

PMID- 22961985
TI  - Protein-protein interactions in the beta-oxidation part of the phenylacetate
      utilization pathway: crystal structure of the PaaF-PaaG hydratase-isomerase
      complex.
AB  - Microbial anaerobic and so-called hybrid pathways for degradation of aromatic
      compounds contain beta-oxidation-like steps. These reactions convert the product
      of the opening of the aromatic ring to common metabolites. The hybrid
      phenylacetate degradation pathway is encoded in Escherichia coli by the paa
      operon containing genes for 10 enzymes. Previously, we have analyzed protein
      protein interactions among the enzymes catalyzing the initial oxidation steps in
      the paa pathway (Grishin, A. M., Ajamian, E., Tao, L., Zhang, L., Menard, R., and
      Cygler, M. (2011) J. Biol. Chem. 286, 10735-10743). Here we report
      characterization of interactions between the remaining enzymes of this pathway
      and show another stable complex, PaaFG, an enoyl-CoA hydratase and enoyl-Coa
      isomerase, both belonging to the crotonase superfamily. These steps are
      biochemically similar to the well studied fatty acid beta-oxidation, which can be
      catalyzed by individual monofunctional enzymes, multifunctional enzymes
      comprising several domains, or enzymatic complexes such as the bacterial fatty
      acid beta-oxidation complex. We have determined the structure of the PaaFG
      complex and determined that although individually PaaF and PaaG are similar to
      enzymes from the fatty acid beta-oxidation pathway, the structure of the complex
      is dissimilar from bacterial fatty acid beta-oxidation complexes. The PaaFG
      complex has a four-layered structure composed of homotrimeric discs of PaaF and
      PaaG. The active sites of PaaF and PaaG are adapted to accept the intermediary
      components of the Paa pathway, different from those of the fatty acid beta
      oxidation. The association of PaaF and PaaG into a stable complex might serve to
      speed up the steps of the pathway following the conversion of phenylacetyl-CoA to
      a toxic and unstable epoxide-CoA by PaaABCE monooxygenase.

PMID- 22961986
TI  - Snail represses the splicing regulator epithelial splicing regulatory protein 1
      to promote epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT), a tightly regulated process that is
      critical for development, is frequently re-activated during cancer metastasis and
      recurrence. We reported previously that CD44 isoform switching is critical for
      EMT and showed that the splicing factor ESRP1 inhibits CD44 isoform switching
      during EMT. However, the mechanism by which ESRP1 is regulated during EMT has not
      been fully understood. Here we show that the transcription repressor Snail binds
      to E-boxes in the ESRP1 promoter, causing repression of the ESRP1 gene.
      Biochemically, we define the mechanism by which ESRP1 regulates CD44 alternative
      splicing: ESRP1 binds to the intronic region flanking a CD44 variable exon and
      causes increased variable exon inclusion. We further show that ectopically
      expressing ESRP1 inhibits Snail-induced EMT, suggesting that down-regulation of
      ESRP1 is required for function by Snail in EMT. Together, these data reveal how
      the transcription factor Snail mediates EMT through regulation of a splicing
      factor.

PMID- 22961988
TI  - Platinum nanoparticles stabilized by cucurbit[6]uril with enhanced catalytic
      activity and excellent poisoning tolerance for methanol electrooxidation.
AB  - Three sub-10 nm platinum nanoparticles (PtNPs) with distinctive morphologies were
      developed by using cucurbit[6]uril (CB[6]) as stabilizing agent and support. Both
      the size and shape of the PtNPs were simultaneously controlled by tuning the
      reducing agents. The prepared NPs have been comprehensively characterized by X
      ray diffraction, X-ray photoelectron spectroscopy, transmission electron
      microscopy, and cyclic voltammetry. On account of the presence of CB[6] and its
      unique structural features, the as-prepared PtNPs are homogeneous in morphologies
      and exhibit higher activities toward methanol electrooxidation than commercial
      Pt/C. CB[6] has the ability to bind small molecules that can promote CO
      oxidation, therefore, all the three PtNPs showed enhanced poisoning tolerance.
      Such unique abilities of CB[6] can even promote the poisoning tolerance of
      commercial Pt/C through simple physical mixing.

PMID- 22961987
TI  - The design and characterization of receptor-selective APRIL variants.
AB  - A proliferation-inducing ligand (APRIL), a member of the TNF ligand superfamily
      with an important role in humoral immunity, is also implicated in several cancers
      as a prosurvival factor. APRIL binds two different TNF receptors, B cell
      maturation antigen (BCMA) and transmembrane activator and cylclophilin ligand
      interactor (TACI), and also interacts independently with heparan sulfate
      proteoglycans. Because APRIL shares binding of the TNF receptors with B cell
      activation factor, separating the precise signaling pathways activated by either
      ligand in a given context has proven quite difficult. In this study, we have used
      the protein design algorithm FoldX to successfully generate a BCMA-specific
      variant of APRIL, APRIL-R206E, and two TACI-selective variants, D132F and D132Y.
      These APRIL variants show selective activity toward their receptors in several in
      vitro assays. Moreover, we have used these ligands to show that BCMA and TACI
      have a distinct role in APRIL-induced B cell stimulation. We conclude that these
      ligands are useful tools for studying APRIL biology in the context of individual
      receptor activation.

PMID- 22961989
TI  - Fluorescent DNA labeling by N-mustard analogues of S-adenosyl-L-methionine.
AB  - Azide and alkyne-functionalized N-mustard analogues of S-adenosyl-L-methionine
      have been synthesized and were demonstrated to undergo efficient
      methyltransferase-dependent DNA alkylation by M.TaqI and M.HhaI. Subsequent
      labeling of the DNA with a fluorophore was carried out using copper-catalyzed
      azide-alkyne cycloaddition chemistry and was visualized by fluorescence scanning.
      This work demonstrates the utility of functionalized N-mustard analogues as
      biochemical tools to study biological methylation and offers a facile way to site
      selectively label substrates of DNA methyltransferases.

PMID- 22961990
TI  - Discovery of a new class of liver receptor homolog-1 (LRH-1) antagonists: virtual
      screening, synthesis and biological evaluation.
AB  - Targeting LRH-1: Virtual screening and molecular modeling were used to identify
      novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic
      target for breast cancer. Hit compounds were synthesized and biologically
      assayed, and the preliminary results suggest that raloxifene-based analogues,
      substituted at the position C-7 of the benzothiophene ring, might generate an
      inactive protein conformation through binding and thus antagonize this nuclear
      receptor. 

PMID- 22961992
TI  - Effect of brief mindfulness intervention on tolerance and distress of pain
      induced by cold-pressor task.
AB  - A number of studies have demonstrated that short-term meditation intervention can
      lead to greater tolerance and lower pain or distress ratings of experimentally
      induced pain. However, few attempts have been made to examine the effects of
      short-term mindfulness-based intervention on the tolerance and distress of pain,
      when delivered in a therapist-free form. The present research explored the effect
      of brief mindfulness intervention using pre-recorded instruction on pain
      experimentally induced by the cold-pressor task. The effects of the mindfulness
      strategy, the distraction strategy and spontaneous strategy, all through the
      instructions of pre-recorded voices, were compared. The subjects were drawn from
      healthy college students and randomly assigned to the aforementioned three
      groups. Our results showed that compared with using spontaneous strategies, the
      mindfulness intervention significantly improved the participants' pain tolerance
      and reduced their immersion distress. The distraction strategy also significantly
      improved the participants' pain tolerance. However, it did not have a significant
      effect on the participants' level of distress during the immersion period. Our
      results suggest that brief mindfulness intervention without a therapist's
      personal involvement is capable of helping people cope with pain induced by the
      cold-pressor task.

PMID- 22961993
TI  - Re-evaluation of prognostic markers including staging, serum free light chains or
      their ratio and serum lactate dehydrogenase in multiple myeloma patients
      receiving novel agents.
AB  - International Staging System (ISS), serum free light chain ratio (sFLCR) and
      lactate dehydrogenase (LDH) are well known, easily assessed independent
      prognostic indicators of outcome in multiple myeloma (MM). The purpose of the
      study was to re-examine the prognostic contribution of these variables in a
      multicenter setting with special attention to MM patients treated with autologous
      stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five
      symptomatic newly diagnosed MM patients were retrospectively studied. Twenty
      seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty
      six per cent of them presented kappa light chain monoclonality; median sFLCR was
      27.04 (0.37-1.9 * 10(5) ) and 47.97 (0.26-2.3 * 10(7) ) for kappa patients and
      lambda patients, respectively; patients with sFLCR above median constituted the
      high sFLCR group. Thirty-one per cent of patients had increased LDH. As first
      line treatment, 55.7% received conventional treatment and 44.3% NA. After
      induction, 24% underwent ASCT, whereas 76% received NA at any line, either
      bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305
      patients were analyzed together, staging, high sFLCR and abnormal LDH were
      predictive of survival. The same was true for patients that never received NA,
      whereas neither high sFLCR nor abnormal LDH constituted adverse factors in
      patients that received NA frontline. In the last group of patients, no difference
      was observed between ISS stages 2 and 3. The median 5-year survival of patients
      that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52%
      and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3,
      respectively (p = 0.03, p < 0.00001 and p = 0.035). In conclusion, patients
      gaining the most from NA are those with an aggressive disease as reflected by
      advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of
      these three variables is obscured by NA.

PMID- 22961994
TI  - The efficacy of mindfulness-based stress reduction on mental health of breast
      cancer patients: a meta-analysis.
AB  - OBJECTIVE: This study aims to investigate the evidence of the efficacy of
      mindfulness-based stress reduction (MBSR) in improving stress, depression and
      anxiety in breast cancer patients. METHODS: An extensive systematic electronic
      review (PubMed, Embase, CINAHL, PsyArticles, PsycINFO, Scopus, Ovid, Web of
      Science and The Cochrane Library) and a hand search were carried out from 15
      October 2011 to 30 November 2011 to retrieve relevant articles using
      'mindfulness' or 'mindfulness-based stress reduction' and 'breast cancer' as
      keywords. Information about the baseline characteristics of the participants,
      interventions and findings on perceived stress, depression and anxiety was
      extracted from each study. RESULTS: Nine published studies (two randomised
      controlled trials, one quasi-experimental case-control study and six one-group,
      pre-intervention and post-intervention studies) up to November 2011 that
      fulfilled the inclusion criteria were analysed. The pooled effect size (95% CI)
      for MBSR on stress was 0.710 (0.511-0.909), on depression was 0.575 (0.429-0.722)
      and on anxiety was 0.733 (0.450-1.017). CONCLUSION: On the basis of these
      findings, MBSR shows a moderate to large positive effect size on the mental
      health of breast cancer patients and warrants further systematic investigation
      because it has a potential to make a significant improvement on mental health for
      women in this group.

PMID- 22961995
TI  - Large-scale colloidal synthesis of non-stoichiometric Cu(2) ZnSnSe(4)
      nanocrystals for thermoelectric applications.
AB  - Over 10 g of non-stoichiometric Cu(2) ZnSnSe(4)  colloidal nanocrystals for
      thermoelectric applications are prepared after one single reaction. The obtained
      pellet made from the colloidal nanocrystals shows a peak ZT value of 0.44 at 450 
      degrees C, which is similar to those of state-of-the-art Cu(2) ZnSnSe(4) -based
      bulk materials at the same temperature.

PMID- 22961996
TI  - Local catalytic ignition during CO oxidation on low-index Pt and Pd surfaces: a
      combined PEEM, MS, and DFT study.

PMID- 22961997
TI  - Flexible CoAl LDH@PEDOT core/shell nanoplatelet array for high-performance energy
      storage.
AB  - A CoAl-layered double hydroxide (LDH)@poly(3,4-ethylenedioxythiophene) (PEDOT)
      core/shell nanoplatelet array (NPA) is grown on a flexible Ni foil substrate as a
      high-performance pseudocapacitor. The LDH@PEDOT core/shell NPA shows a maximum
      specific capacitance of 649 F/g (based on the total mass) by cyclic voltammetry
      (scan rate: 2 mV/s) and 672 F/g by galvanostatic discharge (current density: 1
      A/g). Furthermore, the hybrid NPA electrode also exhibits excellent rate
      capability with a specific energy of 39.4 Wh/kg at a current density of 40 A/g,
      as well as good long-term cycling stability (92.5% of its original capacitance is
      retained after 5000 cycles). These performances are superior to those of
      conventional supercapacitors and LDH NPA without the PEDOT coating. The largely
      enhanced pseudocapacitor behavior of the LDH@PEDOT NPA electrode is related to
      the synergistic effect of its individual components: the LDH nanoplatelet core
      provides abundant energy-storage capacity, while the highly conductive PEDOT
      shell and porous architecture facilitate the electron/mass transport in the redox
      reaction.

PMID- 22961998
TI  - Sulfite action in glycolytic inhibition: in vivo real-time observation by
      hyperpolarized (13)C NMR spectroscopy.
AB  - Detecting the molecular targets of xenobiotic substances in vivo poses a
      considerable analytical challenge. Here, we describe the use of an NMR-based
      tracer methodology for the instantaneous in vivo observation of sulfur(IV) action
      on cellular metabolism. Specifically, we find that glycolytic flux is directed
      towards sulfite adducts of dihydroxyacetone phosphate and pyruvate as off-pathway
      intermediates that obstruct glycolytic flux. In particular, the pyruvate-sulfite
      association hinders the formation of downstream metabolites. The apparent in vivo
      association constant of pyruvate and sulfite agrees with the apparent inhibition
      constant of CO(2)  formation, thus supporting the importance of pyruvate
      interception in disturbing central metabolism and inhibiting NAD regeneration.

PMID- 22961999
TI  - Li+-mediated B-C cross-coupling.
AB  - Easy as A, B-C: B-C cross-coupling on [3,3'-Co(8-I-1,2-C(2)B(9)H(10))(1',2'
      C(2)B(9)H(11))](-), [1](-), the best specimen of metallacarboranes, is easily
      produced in a reaction mediated by Li(+) in the absence of a transition-metal
      catalyst. Pure RLi or a mixture of Li reagents (tBuLi+RLi) is adequate to produce
      the B-C bond. Notably, a threshold of RLi (or tBuLi+RLi)/[1](-), 2:1, is required
      to initiate the B-C coupling, which acts, at least in part, as a source of
      soluble Li(+).

PMID- 22962000
TI  - Structural, electronic, and optical properties of metallo base pairs in duplex
      DNA: a theoretical insight.
AB  - Using density functional theory calculations, we investigated the structural,
      energetic, electronic, and optical properties of recently synthesized duplex DNA
      containing metal-mediated base pairs. The studied duplex DNA consists of three
      imidazole (Im) units linked through metal (Im-M-Im, M = metal) and four flanking
      A:T base pairs (two on each side). We examined the role of artificial base
      pairing in the presence of two distinctive metal ions, diamagnetic Ag(+) and
      magnetic Cu(2+) ions, on the stability of duplex DNA. We found that metal
      mediated base pairs form stable duplex DNA by direct metal ion coordination to
      the Im bases. Our results suggest a higher binding stability of base pairing
      mediated by Cu(2+) ions than by Ag(+) ions, which is attributed to a larger
      extent of orbital hybridization. We furthermore found that DNA modified with Im
      Ag(+)-Im shows the low-energy optical absorption characteristic of pi-pi*orbital
      transition of WC A:T base pairs. On the other hand, we found that the low-energy
      optical absorption peaks for DNA modified with Im-Cu(2+)-Im originate from spin
      spin interactions. Additionally, this complex exhibits weak ferromagnetic
      coupling between Cu(2+) ions and strong spin polarization, which could be used
      for memory devices. Moreover, analyzing the role of counter ions (Na(+)) and the
      presence of explicit water molecules on the structural stability and electronic
      properties of the DNA duplex modified with Im-Ag(+)-Im, we found that the impact
      of these two factors is negligible. Our results are fruitful for understanding
      the experimental data and suggest a potential route for constructing effective
      metal-mediated base pairs in duplex DNA for optoelectronic applications.

PMID- 22962001
TI  - Self-reported racial discrimination and endothelial reactivity to acute stress in
      women.
AB  - This study investigated the effect of self-reported racial discrimination on
      endothelial responses to acute laboratory mental stress among post-menopausal
      women. One-hundred thirteen women (n = 94 self-identified as White and n = 19
      self-identified as racial/ethnic minority), 43% with type 2 diabetes, reported
      lifetime experiences of racial/ethnic discrimination. Repeated assessments of
      flow-mediated dilation were performed at baseline, immediately after 5 min of
      mental arithmetic and at 20-min recovery. Both White and racial/ethnic minority
      women reported lifetime discrimination, with rates significantly higher among
      minorities. Self-reported lifetime discrimination was associated with attenuated
      flow-mediated dilation at recovery. Confounding variables, including clinical
      characteristics, mood, personality traits, other life stressors and general
      distress, did not better account for the effect of racial discrimination. Neither
      race/ethnicity nor diabetes status moderated the effect. The perceived
      stressfulness of the mental arithmetic was not associated with the endothelial
      response. In conclusion, self-reported lifetime discrimination is associated with
      attenuated endothelial recovery from acute mental stress. Elucidating the effects
      of discrimination and the biological mechanisms through which it affects the
      vasculature may suggest interventions to improve health.

PMID- 22962002
TI  - A low elastic modulus Ti-Nb-Hf alloy bioactivated with an elastin-like protein
      based polymer enhances osteoblast cell adhesion and spreading.
AB  - beta-type titanium alloys with low Young's modulus are desirable to reduce stress
      shielding effect and enhance bone remodeling for implants used to substitute
      failed hard tissue. For biomaterials application, the surface bioactivity is
      necessary to achieve optimal osseointegration. In the previous work, the low
      elastic modulus (43 GPa) Ti-25Nb-16Hf (wt %) alloy was mechanically and
      microstructurally characterized. In the present work, the biological behavior of
      Ti-25Nb-16Hf was studied. The biological response was improved by surface
      modification. The metal surface was modified by oxygen plasma and subsequently
      silanized with 3-chloropropyl(triethoxy)silane for covalent immobilization of the
      elastin-like polymer. The elastin-like polymer employed exhibits RGD bioactive
      motives inspired to the extracellular matrix in order to improve cell adhesion
      and spreading. Upon modification, the achieved surface presented different
      physical and chemical properties, such as surface energy and chemical
      composition. Subsequently, osteoblast adhesion, cell numbers, and differentiation
      studies were performed to correlate surface properties and cell response. The
      general tendency was that the higher surface energy the higher cell adhesion.
      Furthermore, cell culture and immunofluorescence microscopy images demonstrated
      that RGD-modified surfaces improved adhesion and spreading of the osteoblast cell
      type.

PMID- 22962004
TI  - Pruning rogue taxa improves phylogenetic accuracy: an efficient algorithm and
      webservice.
AB  - The presence of rogue taxa (rogues) in a set of trees can frequently have a
      negative impact on the results of a bootstrap analysis (e.g., the overall support
      in consensus trees). We introduce an efficient graph-based algorithm for rogue
      taxon identification as well as an interactive webservice implementing this
      algorithm. Compared with our previous method, the new algorithm is up to 4 orders
      of magnitude faster, while returning qualitatively identical results. Because of
      this significant improvement in scalability, the new algorithm can now identify
      substantially more complex and compute-intensive rogue taxon constellations. On a
      large and diverse collection of real-world data sets, we show that our method
      yields better supported reduced/pruned consensus trees than any competing rogue
      taxon identification method. Using the parallel version of our open-source code,
      we successfully identified rogue taxa in a set of 100 trees with 116 334 taxa
      each. For simulated data sets, we show that when removing/pruning rogue taxa with
      our method from a tree set, we consistently obtain bootstrap consensus trees as
      well as maximum-likelihood trees that are topologically closer to the respective
      true trees.

PMID- 22962003
TI  - Deficits in mental state attributions in individuals with 22q11.2 deletion
      syndrome (velo-cardio-facial syndrome).
AB  - Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) results from a
      genetic mutation that increases risk for Autism Spectrum Disorder (ASD). We
      compared Theory of Mind (ToM) skills in 63 individuals with VCFS (25% with an ASD
      diagnosis) and 43 typically developing controls, and investigated the
      relationship of ToM to reciprocal social behavior. We administered a video-based
      task to assess mentalizing at two sites University of California, Los Angeles
      (UCLA) and State University of New York (SUNY) Upstate Medical University. The
      videos depicted interactions representing complex mental states (ToM condition),
      or simple movements (Random condition). Verbal descriptions of the videos were
      rated for Intentionality (i.e. mentalizing) and Appropriateness. Using Repeated
      Measures analysis of variance (ANOVA), we assessed the effects of VCFS and ASD on
      Intentionality and Appropriateness, and the relationship of mentalizing to Social
      Responsiveness Scale (SRS) scores. Results indicated that individuals with VCFS
      overall had lower Intentionality and Appropriateness scores than controls for ToM
      but not for Random scenes. In the SUNY sample, individuals with VCFS, both with
      and without ASD, performed more poorly than controls on the ToM condition;
      however, in the UCLA sample, only individuals with VCFS without ASD performed
      significantly worse than controls on the ToM condition. Controlling for site and
      age, performance on the ToM condition was significantly correlated with SRS
      scores. Individuals with VCFS, regardless of an ASD diagnosis, showed impairments
      in the spontaneous attribution of mental states to abstract visual stimuli, which
      may underlie real-life problems with social interactions. A better understanding
      of the social deficits in VCFS is essential for the development of targeted
      behavioral interventions.

PMID- 22962005
TI  - Serine codon-usage bias in deep phylogenomics: pancrustacean relationships as a
      case study.
AB  - Phylogenomic analyses of ancient relationships are usually performed using amino
      acid data, but it is unclear whether amino acids or nucleotides should be
      preferred. With the 2-fold aim of addressing this problem and clarifying
      pancrustacean relationships, we explored the signals in the 62 protein-coding
      genes carefully assembled by Regier et al. in 2010. With reference to the
      pancrustaceans, this data set infers a highly supported nucleotide tree that is
      substantially different to the corresponding, but poorly supported, amino acid
      one. We show that the discrepancy between the nucleotide-based and the amino
      acids-based trees is caused by substitutions within synonymous codon families
      (especially those of serine-TCN and AGY). We show that different arthropod
      lineages are differentially biased in their usage of serine, arginine, and
      leucine synonymous codons, and that the serine bias is correlated with the
      topology derived from the nucleotides, but not the amino acids. We suggest that a
      parallel, partially compositionally driven, synonymous codon-usage bias affects
      the nucleotide topology. As substitutions between serine codon families can
      proceed through threonine or cysteine intermediates, amino acid data sets might
      also be affected by the serine codon-usage bias. We suggest that a Dayhoff
      recoding strategy would partially ameliorate the effects of such bias. Although
      amino acids provide an alternative hypothesis of pancrustacean relationships,
      neither the nucleotides nor the amino acids version of this data set seems to
      bring enough genuine phylogenetic information to robustly resolve the
      relationships within group, which should still be considered unresolved.

PMID- 22962006
TI  - Psychopathological characteristics of child pornographers and their victims: a
      literature review.
AB  - Child pornography is a form of child sexual exploitation which has been modified
      by the use of the Internet. The use of child pornography does not necessarily
      lead to actual child abuse. Victims of child pornography can be classified as
      direct victims, who have been sexually abused, and indirect victims, who receive
      images to groom them for actual abuse in the future. Based on a review of the
      literature, we present the psychopathological characteristics of child
      pornographers and their victims.

PMID- 22962008
TI  - Prednisolone-glucose derivative conjugate: synthesis, biodistribution and
      pharmacodynamics evaluation.
AB  - This study was aimed at synthesizing and evaluating a prednisolone-glucose
      derivative conjugate (PDG) that was expected to increase renal biodistribution
      without affecting pharmacological action and to decrease the systemic side
      effects of prednisolone. The PDG was designed and synthesized by tethering 6
      amino-6-deoxy-D-glucose (a D-glucose derivative) to prednisolone and its chemical
      structure was confirmed by (1) H NMR, (13) C NMR, and LC-MS. This conjugate was
      then subjected to in vitro and in vivo evaluation like stability studies,
      biological distribution, pharmacodynamics, and systemic side effects studies. In
      these studies, PDG not only showed significant enhancement of renal target
      efficiency with high values of relative uptake efficiency (RE, 24.1),
      concentration efficiency (CE, 8.6), and kidney targeting index (KTI, 16.3), but
      retained the curative potency against minimal change nephrosis (MCN). In the
      systemic side effects study, no osteoporosis was observed in rats after the
      administration of PDG for 20 days, which exhibited limited side effects.
      Conclusively, our findings showed a pharmacologically active conjugate with the
      characteristics of renal targeting and limited systemic side effects. The results
      implied the potential of PDG as a promising therapeutic in the treatment of renal
      diseases.

PMID- 22962009
TI  - Synthesis of fluorinated tricyclic scaffolds by intramolecular [2+2]
      photocycloaddition reactions.

PMID- 22962007
TI  - Gene duplication and the evolution of hemoglobin isoform differentiation in
      birds.
AB  - The majority of bird species co-express two functionally distinct hemoglobin (Hb)
      isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform,
      with alpha-chain subunits encoded by the alpha(A)-globin gene) and HbD (the minor
      adult Hb isoform, with alpha-chain subunits encoded by the alpha(D)-globin gene).
      The alpha(D)-globin gene originated via tandem duplication of an embryonic alpha
      like globin gene in the stem lineage of tetrapod vertebrates, which suggests the
      possibility that functional differentiation between the HbA and HbD isoforms may
      be attributable to a retained ancestral character state in HbD that harkens back
      to a primordial, embryonic function. To investigate this possibility, we
      conducted a combined analysis of protein biochemistry and sequence evolution to
      characterize the structural and functional basis of Hb isoform differentiation in
      birds. Functional experiments involving purified HbA and HbD isoforms from 11
      different bird species revealed that HbD is characterized by a consistently
      higher O(2) affinity in the presence of allosteric effectors such as organic
      phosphates and Cl(-) ions. In the case of both HbA and HbD, analyses of
      oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model
      revealed that the pH dependence of Hb-O(2) affinity stems primarily from changes
      in the O(2) association constant of deoxy (T-state)-Hb. Ancestral sequence
      reconstructions revealed that the amino acid substitutions that distinguish the
      adult-expressed Hb isoforms are not attributable to the retention of an ancestral
      (pre-duplication) character state in the alpha(D)-globin gene that is shared with
      the embryonic alpha-like globin gene.

PMID- 22962011
TI  - Implication of the ryanodine receptor in TRPV4-induced calcium response in
      pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic
      rats.
AB  - There is a growing body of evidence indicating that transient receptor potential
      (TRP) channels are implicated in calcium signaling and various cellular functions
      in the pulmonary vasculature. The aim of this study was to investigate the
      expression, functional role, and coupling to reticulum calcium channels of the
      type 4 vanilloid TRP subfamily (TRPV4) in the pulmonary artery from both normoxic
      (Nx) and chronically hypoxic (CH) rats. Activation of TRPV4 with the specific
      agonist 4alpha-phorbol-12,13-didecanoate (4alpha-PDD, 5 MUM) increased the
      intracellular calcium concentration ([Ca(2+)](i)). This effect was significantly
      reduced by a high concentration of ryanodine (100 MUM) or chronic caffeine (5 mM)
      that blocked ryanodine receptor (RyR) but was insensitive to xestospongin C (10
      MUM), an inositol trisphosphate receptor antagonist. Inhibition of RyR1 and RyR3
      only with 10 MUM of dantrolene did not attenuate the 4alpha-PDD-induced
      [Ca(2+)](i) increase. Western blotting experiments revealed the expression of
      TRPV4 and RyR2 with an increase in both receptors in pulmonary arteries from CH
      rats vs. Nx rats. Accordingly, the 4alpha-PDD-activated current, measured with
      patch-clamp technique, was increased in pulmonary artery smooth muscle cells
      (PASMC) from CH rats vs. Nx rats. 4alpha-PDD increased isometric tension in
      artery rings, and this response was also potentiated under chronic hypoxia
      conditions. 4alpha-PDD-induced calcium response, current, and contraction were
      all inhibited by the selective TRPV4 blocker HC-067047. Collectively, our
      findings provide evidence of the interplay between TRPV4 and RyR2 in the Ca(2+)
      release mechanism and contraction in PASMC. This study provides new insights onto
      the complex calcium signaling in PASMC and point out the importance of the TRPV4
      RyR2 signaling pathway under hypoxic conditions that may lead to pulmonary
      hypertension.

PMID- 22962010
TI  - LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling
      in the ovine fetal lung.
AB  - Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally
      but disrupt late-gestation lung development. Because Sonic Hedgehog (Shh)
      signaling is a major pathway directing lung development, we hypothesized that
      chorioamnionitis and antenatal corticosteroids modulated Shh signaling, resulting
      in an altered fetal lung structure. Time-mated ewes with singleton ovine fetuses
      received an intra-amniotic injection of lipopolysaccharide (LPS) and/or maternal
      intramuscular betamethasone 7 and/or 14 days before delivery at 120 days
      gestational age (GA) (term = 150 days GA). Intra-amniotic LPS exposure decreased
      Shh mRNA levels and Gli1 protein expression, which was counteracted by both
      betamethasone pre- or posttreatment. mRNA and protein levels of fibroblast growth
      factor 10 and bone morphogenetic protein 4, which are important mediators of lung
      development, increased 2-fold and 3.5-fold, respectively, 14 days after LPS
      exposure. Both 7-day and 14-day exposure to LPS changed the mRNA levels of
      elastin (ELN) and collagen type I alpha 1 (Col1A1) and 2 (Col1A2), which resulted
      in fewer elastin foci and increased collagen type I deposition in the alveolar
      septa. Corticosteroid posttreatment prevented the decrease in ELN mRNA and
      increased elastin foci and decreased collagen type I deposition in the fetal
      lung. In conclusion, fetal lung exposure to LPS was accompanied by changes in key
      modulators of lung development resulting in abnormal lung structure.
      Betamethasone treatment partially prevented the changes in developmental
      processes and lung structure. This study provides new insights into clinically
      relevant prenatal exposures and fetal lung development.

PMID- 22962012
TI  - Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated
      Ca2+ sparks in fetal sheep pulmonary arterial myocytes.
AB  - Ca(2+) sparks are fundamental Ca(2+) signaling events arising from ryanodine
      receptor (RyR) activation, events that relate to contractile and dilatory events
      in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia
      (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult
      animals. Because RyRs are important to pulmonary vascular reactivity and
      reactivity changes with ontogeny and LTH we tested the hypothesis that RyR
      generated Ca(2+) signals are more active before birth and that LTH suppresses
      these responses. We examined these hypotheses by performing confocal imaging of
      myocytes in living arteries and by performing wire myography studies. Pulmonary
      arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low
      altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal
      imaging demonstrated preservation of the distance between the sarcoplasmic
      reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased
      global Ca(2+) waves and Ca(2+) spark activity, with sparks becoming larger,
      wider, and slower. LTH preferentially depressed Ca(2+) spark activity in immature
      pulmonary arterial myocytes, and these sparks were smaller, wider, and slower.
      LTH also suppressed caffeine-elicited contraction in fetal PA but augmented
      contraction in the newborn and adult. The influence of both ontogeny and LTH on
      RyR-dependent cell excitability shed new light on the therapeutic potential of
      these channels for the treatment of pulmonary vascular disease in newborns as
      well as adults.

PMID- 22962013
TI  - Acute cigarette smoke exposure impairs proteasome function in the lung.
AB  - Cigarette smoke mediates DNA damage, lipid peroxidation, and modification and
      misfolding of proteins, thereby inducing severe cellular damage. The ubiquitin
      proteasome system serves as the major disposal system for modified and misfolded
      proteins and is thus essential for proper cellular function. Its role in
      cigarette smoke-induced cell damage, however, is largely unknown. We hypothesized
      that the ubiquitin-proteasome system is involved in the degradation of cigarette
      smoke-damaged proteins and that cigarette smoke exposure impairs the proteasome
      itself. Here, we show that treatment of human alveolar epithelial cells with
      cigarette smoke extract (CSE) induced time- and dose-dependent cell death, a rise
      in intracellular reactive oxygen species, and increased levels of carbonylated
      and polyubiquitinated proteins. While high doses of CSE severely impaired all
      three proteasomal activities, low CSE concentrations significantly inhibited only
      the trypsin-like activity of the proteasome in alveolar and bronchial epithelial
      cells. Moreover, acute exposure of mice to cigarette smoke significantly impaired
      the trypsin-like activity by 25% in the lungs. Reduced proteasome activity was
      not due to transcriptional regulation of the proteasome. Notably, cigarette smoke
      exposure induced accumulation of polyubiquitinated proteins in the soluble and
      insoluble protein fraction of the lung. We show for the first time that acute
      exposure to cigarette smoke directly impairs proteasome activity in the lungs of
      mice and in human epithelial cells at low doses without affecting proteasome
      expression. Our results indicate that defective proteasomal protein quality
      control may exacerbate the detrimental effects of cigarette smoke in the lung.

PMID- 22962014
TI  - Annexin V decreases PS-mediated macrophage efferocytosis and deteriorates
      elastase-induced pulmonary emphysema in mice.
AB  - Efferocytosis is believed to be a key regulator for lung inflammation in chronic
      obstructive pulmonary disease. In this study we pharmacologically inhibited
      efferocytosis with annexin V and attempted to determine its impact on the
      progression of pulmonary emphysema in mouse. We first demonstrated in vitro and
      in vivo efferocytosis experiments using annexin V, an inhibitor for
      phosphatidylserine-mediated efferocytosis. We then inhibited efferocytosis in
      porcine pancreatic elastase (PPE)-treated mice. PPE-treated mice were instilled
      annexin V intranasally starting from day 8 until day 20. Mean linear intercept
      (Lm) was measured, and cell apoptosis was assessed in lung specimen obtained on
      day 21. Cell profile, apoptosis, and mRNA expression of matrix metalloproteinases
      (MMPs) and growth factors were evaluated in bronchoalveolar lavage (BAL) cells on
      day 15. Annexin V attenuated macrophage efferocytosis both in vitro and in vivo.
      PPE-treated mice had a significant higher Lm, and annexin V further increased
      that by 32%. More number of macrophages was found in BAL fluid in this group.
      Interestingly, cell apoptosis was not increased by annexin V treatment both in
      lung specimens and BAL fluid, but macrophages from mice treated with both PPE and
      annexin V expressed higher MMP-2 mRNA levels and had a trend for higher MMP-12
      mRNA expression. mRNA expression of keratinocyte growth factor tended to be
      downregulated. We showed that inhibited efferocytosis with annexin V worsened
      elastase-induced pulmonary emphysema in mice, which was, at least partly,
      attributed to a lack of phenotypic change in macrophages toward anti-inflammatory
      one.

PMID- 22962015
TI  - Decreases in manganese superoxide dismutase expression and activity contribute to
      oxidative stress in persistent pulmonary hypertension of the newborn.
AB  - A rapid increase in the synthesis and release of nitric oxide (NO) facilitates
      the pulmonary vasodilation that occurs during birth-related transition.
      Alteration of this transition in persistent pulmonary hypertension of the newborn
      (PPHN) is associated with impaired function of endothelial nitric oxide synthase
      (eNOS) and an increase in oxidative stress. We investigated the hypothesis that a
      decrease in expression and activity of mitochondrial localized manganese
      superoxide dismutase (MnSOD) in pulmonary artery endothelial cells (PAEC)
      increases oxidative stress and impairs eNOS function in PPHN. We isolated PAEC
      and pulmonary arteries from fetal lambs with PPHN induced by prenatal ductus
      arteriosus ligation or sham ligation (control). We investigated MnSOD expression
      and activity, tyrosine nitration of MnSOD, and mitochondrial O(2)(-) levels in
      PAEC from control and PPHN lambs. We introduced exogenous MnSOD via an adenoviral
      vector (ad-MnSOD) transduction into PAEC and pulmonary arteries of PPHN lambs.
      The effect of ad-MnSOD was investigated on: mitochondrial O(2)(-) levels, MnSOD
      and eNOS expression and activity, intracellular hydrogen peroxide (H(2)O(2))
      levels, and catalase expression in PAEC. MnSOD mRNA and protein levels and
      activity were decreased and MnSOD tyrosine nitration was increased in PPHN-PAEC.
      ad-MnSOD transduction of PPHN-PAEC increased its activity two- to threefold,
      decreased mitochondrial O(2)(-) levels, and increased H(2)O(2) levels and
      catalase expression. ad-MnSOD transduction improved eNOS expression and function
      and the relaxation response of PPHN pulmonary arteries. Our observations suggest
      that decreased MnSOD expression and activity contribute to the endothelial
      dysfunction observed in PPHN.

PMID- 22962016
TI  - The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display
      distinct patterns of relaxation of the guinea pig trachea.
AB  - Activation of taste receptors (TAS2Rs) by bitter taste agonists has been reported
      to cause bronchodilation. The aim of this study was to extend the information on
      the effects of bitter taste agonists on responses induced by different
      contractile mediators in a standard airway physiology preparation. Isometric
      responses were assessed in guinea pig trachea (GPT). TAS2R agonists were
      administered either to segments precontracted with different agonists for
      contraction or given before challenge with the different contractile stimuli,
      including antigen in tissues from ovalbumin-sensitized animals. TAS2R mRNA
      expression on GPT epithelium and smooth muscle was measured with real-time PCR.
      Denatonium, chloroquine, thiamine, and noscapine induced concentration-dependent
      relaxations (R(max): 98.3 +/- 1.6, 100.0 +/- 0.0, 100.0 +/- 0.0, and 52.3 +/-
      1.1% of maximum, respectively, in the presence of indomethacin) in segments
      precontracted with carbachol. The receptors for denatonium (TAS2R4, TAS2R10) and
      chloroquine (TAS2R3, TAS2R10) were expressed in GPT. Whereas denatonium
      selectively inhibited contractions induced by carbachol, chloroquine uniformly
      inhibited contractions evoked by prostaglandin E(2), the thromboxane receptor
      agonist U-46619, leukotriene D(4), histamine, and antigen. The effects of
      denatonium, but not those of chloroquine, were partly inhibited by blockers of
      the large Ca(2+)-activated K(+) channels and decreased by an increase of the
      level of precontraction. In conclusion, TAS2R agonists mediated strong
      relaxations and substantial inhibition of contractions in GPT. Chloroquine and
      denatonium had distinct patterns of activity, indicating different signaling
      mechanisms. The findings reinforce the hypothesis that TAS2Rs are potential
      targets for the development of a new class of more efficacious agonists for
      bronchodilation.

PMID- 22962017
TI  - Pulmonary research in 2013 and beyond: a National Heart, Lung, and Blood
      Institute perspective.

PMID- 22962018
TI  - Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric
      dysfunction.
AB  - We previously demonstrated that diaphragm muscle weakness is present in
      experimental pulmonary arterial hypertension (PH). However, the nature of this
      diaphragm weakness is still unknown. Therefore, the aim of this study was to
      investigate whether changes at the sarcomeric level contribute to diaphragm
      weakness in PH. For this purpose, in control rats and rats with monocrotaline
      induced PH, contractile performance and myosin heavy chain content of
      demembranated single diaphragm fibers were determined. We observed a reduced
      maximal tension of 20% (P < 0.05), whereas tension cost was preserved in type 2X
      and 2B diaphragm fibers in PH compared with control. The reduced maximal tension
      was associated with a reduction of force generated per half-sarcomeric myosin
      heavy chain content. Additionally, reduced Ca(2+) sensitivity of force generation
      was found in type 2X fibers compared with control, which could exacerbate
      diaphragm muscle weakness at submaximal activation. No changes in maximal tension
      and Ca(2+) sensitivity of force generation were observed in fibers from the
      nonrespiratory extensor digitorum longus muscle. Together, these findings
      indicate that diaphragm weakness in PH is at least partly caused by sarcomeric
      dysfunction, which appears to be specific for the diaphragm.

PMID- 22962020
TI  - Truth telling in medical practice: students' opinions versus their observations
      of attending physicians' clinical practice.
AB  - OBJECTIVE: Truth telling or transmitting bad news is a problem that all doctors
      must frequently face. The purpose of this cross-sectional study was to
      investigate if medical students' opinions of truth telling differed from their
      observations of attending physicians' actual clinical practice. METHODS: The
      subjects were 275 medical clerks/interns at a medical center in northern Taiwan.
      Data were collected on medical students' opinions of truth telling, their
      observations of physicians' clinical practice, students' level of satisfaction
      with truth telling practiced by attending physicians, and cancer patients'
      distress level when they were told the truth. RESULTS: Students' truth-telling
      awareness was significantly higher than the clinical truth-telling practice of
      attending physicians (p<0.001), and the means for these parameters had a moderate
      difference, especially in three aspects: method, emotional support, and providing
      additional information (p<0.001). Regardless of this difference, students were
      satisfied with the truth telling of attending physicians (mean +/- SD=7.33 +/-
      1.74). However, our data also show that when cancer patients were informed of bad
      news, they all experienced medium to above average distress (5.93 +/- 2.19).
      CONCLUSIONS: To develop the ability to tell the truth well, one must receive
      regular training in communication skills, including experienced attending
      physicians. This study found a significant difference between medical students'
      opinions on truth telling and attending physicians' actual clinical practice.
      More research is needed to objectively assess physicians' truth telling in
      clinical practice and to study the factors affecting the method of truth telling
      used by attending physicians in clinical practice.

PMID- 22962019
TI  - Multi-reservoir bioadhesive microdevices for independent rate-controlled delivery
      of multiple drugs.
AB  - A variety of oral administrative systems such as enterically coated tablets,
      capsules, particles, and liposomes have been developed to improve oral
      bioavailability of drugs. However, they suffer from poor intestinal localization
      and therapeutic efficacy due to the various physiological conditions and high
      shear fluid flow. Fabrication of novel microdevices combined with the
      introduction of controlled release, improved adhesion, selective targeting, and
      tissue permeation may overcome these issues and potentially diminish the toxicity
      and high frequency of conventional oral administration. Herein, thin, asymmetric,
      poly(methyl methacrylate) (PMMA) microdevices are fabricated with multiple
      reservoirs using photolithography and reactive ion etching. They are loaded with
      different individual model drug in each reservoir. Enhanced bioadhesion of the
      microdevices is observed in the presence of a conjugated of targeting protein
      (tomato lectin) to the PMMA surface. As compared to drug encompassing hydrogels,
      an increase in drug permeation across the caco-2 monolayer is noticed in the
      presence of a microdevice loaded with the same drug-hydrogel system. Also, the
      release of multiple drugs from their respective reservoirs is found to be
      independent from each other. The use of different hydrogel systems in each
      reservoir shows differences in the controlled release of the respective drugs
      over the same release period. These results suggest that, in the future,
      microfabricated unidirectional multi-drug releasing devices will have an impact
      on the oral administration of a broad range of therapeutics.

PMID- 22962021
TI  - Reversible double C-H bond activation of linear and cyclic ethers to form iridium
      carbenes.
AB  - The double C-H bond activation of a series of linear and cyclic ethers by the
      iridium complex [Tp(tol')Ir(C(6)H(5))(N(2))] (2?N(2)), which features a
      cyclometalated hydrotris(3-p-tolylpyrazol-1-yl)borate ligand (Tp(tol'))
      coordinated in a kappa(4)-N,N',N'',C manner, has been studied. Two methyl ethers,
      namely, Me(2)O and MeOtBu, along with diethyl ether and the cyclic ethers
      tetrahydrofuran, tetrahydropyran (THP), and 1,4-dioxane have been investigated
      with formation in every case of the corresponding hydride carbene complexes 3-8,
      which are stabilized by kappa(4)-coordination of the ancillary Tp(tol') ligand.
      Five of the compounds have been structurally authenticated by X-ray
      crystallography. A remarkable feature of these rearrangements is the
      reversibility of the double C-H bond activation of Me(2)O, MeOtBu, Et(2)O, and
      THP. This has permitted catalytic deuterium incorporation into the methyl groups
      of the two methyl ethers, although in a rather inefficient manner (for synthetic
      purposes). Although possible in all cases, C-C coupling by migratory insertion of
      the carbene into the Ir-C sigma bond of the metalated linkage has only been
      observed for complex 8 that contains a cyclic carbene that results from
      alpha,alpha-C-H activation of 1,4-dioxane. Computational studies on the formation
      of iridium carbenes are also reported, which show a role for metalated Tp ligands
      in the double C-H activation and account for the reversibility of the reaction in
      terms of the relative stability of the reagents and the products of the reaction.

PMID- 22962022
TI  - Template-free hydrothermal synthesis of mesoporous MgO nanostructures and their
      applications in water treatment.
AB  - The controlled synthesis of Mg(OH)(2) nanowires and microflowers composed of
      nanoplates was successfully achieved by a template-free hydrothermal synthetic
      method. It was found that the reaction medium played a crucial role in the
      morphological control of the precursor nanostructures. The high polarity of water
      molecules favored the polar growth of the precursor, resulting in the formation
      of nanowires with a diameter of 80 nm, whereas a mixed water/ethanol medium with
      a lower degree of polarity led to the formation of microflowers. Moreover,
      mesoporous MgO nanostructures could be obtained by further annealing these as
      prepared precursors in air at 500  degrees C for 2 h. During thermal treatment,
      the wire- and flower-like morphologies were retained. Porosity formation was due
      to thermal decomposition of Mg(OH)(2) and release of H(2)O. Both the mesoporous
      MgO nanowires and microflowers showed superior ability of adsorbing the organic
      dye methyl orange, and thus they are promising candidates for polluted water
      treatment.

PMID- 22962023
TI  - Characterization of polyurethane scaffold surface functionalization with diamines
      and heparin.
AB  - Polyurethane scaffolds (PUs) have a good biocompatibility but lack cell
      recognition sites. In this study, we functionalized the surface of a PU, P(D/L)LA
      and PCL (50:50) containing urethane segments, with heparin. The first step in
      this functionalization, aminolysis, lead to free amine groups on the surface of
      the PU. Free amine content was determined to be 6.4 nmol/mL/mg scaffold, a
      significant increase of 230%. Subsequently, heparin was crosslinked.
      Immunohistochemistry demonstrated the presence of heparin homogeneous throughout
      the 3D porous scaffold. Young's modulus decreased significantly till 50% of the
      native stiffness after aminolysis and did not change after heparin crosslinking.
      Contact angle on PU films significantly decreased from 82.7 degrees  to 64.3
      degrees  after heparin crosslinking, indicating a more hydrophilic surface. This
      functionalization beholds great potential for tissue engineering purposes. When
      used in a load-bearing environment, caution is necessary due to reduction in
      mechanical stiffness.

PMID- 22962024
TI  - A structured approach to choosing estimands and estimators in longitudinal
      clinical trials.
AB  - An important evolution in the missing data arena has been the recognition of need
      for clarity in objectives. The objectives of primary focus in clinical trials can
      often be categorized as assessing efficacy or effectiveness. The present
      investigation illustrated a structured framework for choosing estimands and
      estimators when testing investigational drugs to treat the symptoms of chronic
      illnesses. Key issues were discussed and illustrated using a reanalysis of the
      confirmatory trials from a new drug application in depression. The primary
      analysis used a likelihood-based approach to assess efficacy: mean change to the
      planned endpoint of the trial assuming patients stayed on drug. Secondarily,
      effectiveness was assessed using a multiple imputation approach. The imputation
      model-derived solely from the placebo group-was used to impute missing values for
      both the drug and placebo groups. Therefore, this so-called placebo multiple
      imputation (a.k.a. controlled imputation) approach assumed patients had reduced
      benefit from the drug after discontinuing it. Results from the example data
      provided clear evidence of efficacy for the experimental drug and characterized
      its effectiveness. Data after discontinuation of study medication were not
      required for these analyses. Given the idiosyncratic nature of drug development,
      no estimand or approach is universally appropriate. However, the general practice
      of pairing efficacy and effectiveness estimands may often be useful in
      understanding the overall risks and benefits of a drug. Controlled imputation
      approaches, such as placebo multiple imputation, can be a flexible and
      transparent framework for formulating primary analyses of effectiveness estimands
      and sensitivity analyses for efficacy estimands.

PMID- 22962025
TI  - Synthesis of manganese ferrite/graphene oxide nanocomposites for biomedical
      applications.
AB  - In this study, MnFe(2)O(4) nanoparticle (MFNP)-decorated graphene oxide
      nanocomposites (MGONCs) are prepared through a simple mini-emulsion and solvent
      evaporation process. It is demonstrated that the loading of magnetic nanocrystals
      can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On
      top of that, the hydrodynamic size range of the obtained nanocomposites can be
      optimized by varying the sonication time during the emulsion process. By fine
      tuning the sonication time, MGONCs as small as 56.8 +/- 1.1 nm, 55.0 +/- 0.6 nm
      and 56.2 +/- 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are
      successfully fabricated. In order to improve the colloidal stability of MGONCs in
      physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs
      are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs
      samples to an alternating magnetic field (AMF) show that the obtained
      nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1
      mg Fe mL(-1) and under an 59.99 kA m(-1) field, the highest specific absorption
      rate (SAR) recorded is 1588.83 W g(-1) for MGONCs loaded with 14 nm MFNPs. It is
      also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI)
      T(2) contrast agents. A T(2) relaxivity value (r(2) ) as high as 256.2 (mM Fe)(
      1) s(-1) could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity
      results show that PEGylated MGONCs exhibit an excellent biocompatibility that is
      suitable for biomedical applications.

PMID- 22962026
TI  - Evaluation of the different strategies to oral cancer knowledge: a randomized
      controlled study.
AB  - OBJECTIVES: Oral cavity and pharyngeal cancer has been well recognized as a
      public health problem. Prognosis for oral cancer is substantially improved when
      diagnosed early. A study was made of the impact of different educational
      strategies upon knowledge of oral cancer, evaluating the intervention after 4
      weeks. METHODS: Ninety subjects over 40 years of age were consecutively included
      and randomized to three different groups (video, leaflet, verbal information).
      All subjects completed a 20-item pre-test on their knowledge of the risk factors,
      signs, and symptoms of oral cancer, and posteriorly received the video, leaflet,
      or verbal information, with evaluation of the results after 4 weeks. RESULTS: In
      relation to the items correctly answered at baseline, all subjects showed an
      increase in knowledge score after 4 weeks: verbal information 4.77 +/- 3.31,
      leaflets 4.53 +/- 3.44, and video 3.67 +/- 3.31 - no statistically significant
      differences being observed for any of the three strategies. CONCLUSION: The oral
      cancer knowledge score increased following the educational intervention, which
      proved successful over the short term.

PMID- 22962027
TI  - Synthesis and characterization of the N-terminal acetylated 17-23 fragment of
      thymosin beta 4 identified in TB-500, a product suspected to possess doping
      potential.
AB  - The formulation TB-500 is suspected to be used as doping agent in sport. This
      work describes the detection and the identification of the N-terminal acetylated
      17-23 fragment of human thymosin beta 4 (Ac-LKKTETQ) in TB-500 by means of high
      performance liquid chromatography/high resolution mass spectrometry using an
      Orbitrap Exactive benchtop mass spectrometer. Ac-LKKTETQ was also synthesized by
      solid-phase peptide synthesis, and an analytical strategy for detection in plasma
      and urine by high-performance liquid chromatography/low resolution triple
      quadrupole mass spectrometry was suggested.

PMID- 22962028
TI  - Development of a peptide that selectively activates protein phosphatase-1 in
      living cells.

PMID- 22962029
TI  - Inverting the regioselectivity of the berberine bridge enzyme by employing
      customized fluorine-containing substrates.
AB  - Fluorine is commonly applied in pharmaceuticals to block the degradation of
      bioactive compounds at a specific site of the molecule. Blocking of the reaction
      center of the enzyme-catalyzed ring closure of 1,2,3,4
      tetrahydrobenzylisoquinolines by a fluoro moiety allowed redirecting the
      berberine bridge enzyme (BBE)-catalyzed transformation of these compounds to give
      the formation of an alternative regioisomeric product namely 11-hydroxy
      functionalized tetrahydroprotoberberines instead of the commonly formed 9-hydroxy
      functionalized products. Alternative strategies to change the regioselectivity of
      the enzyme, such as protein engineering, were not applicable in this special case
      due to missing substrate-enzyme interactions. Medium engineering, as another
      possible strategy, had clear influence on the regioselectivity of the reaction
      pathway, but did not lead to perfect selectivity. Thus, only substrate tuning by
      introducing a fluoro moiety at one potential reactive carbon center switched the
      reaction to the formation of exclusively one regioisomer with perfect
      enantioselectivity.

PMID- 22962030
TI  - Treatment response in type 2 diabetes patients with major depression.
AB  - AIMS: Major depression is more prevalent in patients with type 2 diabetes
      mellitus (T2DM) than in general population. Comparing psychotherapeutic and
      pharmacological treatment responses could help to inform the choice between
      available treatment options. METHOD: Thirty-four patients with T2DM and major
      depression detected by using the Hospital Anxiety-Depression Scale (HADS), the
      Montgomery-Asberg Depression Rating Scale (MADRS) and a structured interview
      (Mini-International Neuropsychiatric Interview) were randomized to undergo
      Interpersonal Psychotherapy (IPT) or treatment with sertraline in a 3-month acute
      intervention course in addition to a 3-month continuation format. Provided that
      the initial MADRS score was not reduced >=25% at week 6, these early non
      responding patients continued treatment in a sequential add-on combined format.
      Psychological adjustment to diabetes, attachment style, diabetes self-efficacy,
      quality of life and HbA1c were also evaluated along intervention. RESULTS: Out of
      22 early-responding patients (11 for each treatment type), 16 had clinically
      significant improvements (<50% initial MADRS score) at endpoint with 11 reaching
      remission (MADRS scores <=8), and with no significant differences between IPT and
      sertraline. Within sequential add-on treatment, out of eight patients, only three
      of them achieved a clinically significant improvement and only one reached
      remission. CONCLUSIONS: These preliminary results suggested that IPT may be an
      option to treat major depression in T2DM against medical care with sertraline.
      Early non-responding patients likely need alternative or longer treatment
      interventions. Limitations of this study relate to small sample and absence of a
      control group, which was difficult to implement due to ethical restrictions. KEY
      PRACTITIONER MESSAGE: Findings suggest that Interpersonal Psychotherapy is a
      useful tool to treat major depression in type 2 diabetes patients. A significant
      number of type 2 diabetes patients with major depression do not achieve
      depression remission irrespective of the type of treatment. Further clinical
      research should focus on addictive effects of psychotherapy and
      psychopharmacology in the treatment of depressed patients with chronic somatic
      diseases.

PMID- 22962031
TI  - Fat on the brain.

PMID- 22962032
TI  - The carotid body in cardiovascular disease: more chicken and egg than horse and
      cart?

PMID- 22962033
TI  - Can exercise prevent coronary artery disease even on a high fat diet?

PMID- 22962034
TI  - Exercise: where the body leads and the heart must follow.

PMID- 22962035
TI  - Orai channels - new insights, new ideas.

PMID- 22962036
TI  - Application of a stochastic model to response assessments in a study of squamous
      cell carcinoma of the head and neck.
AB  - This paper discusses the application of a stochastic model in the analysis of
      response assessments made at various time points in a clinical trial of patients
      with squamous cell carcinoma of the head and neck. The transition rates and
      probabilities during treatment administration are derived using maximum
      likelihood methods. The results are then compared with the standard analyses used
      in solid tumour studies. Stochastic modelling is considered to complement the
      standard analyses, provide a holistic approach and better explain the underlying
      disease process.

PMID- 22962037
TI  - Calcium phosphate cements loaded with basic fibroblast growth factor: delivery
      and in vitro cell response.
AB  - Combining calcium phosphate cements (CPCs) with bioactive molecules improves
      their bone regeneration potential. Although CPCs are highly osteoconductive,
      sometimes they have limited biological responses, especially in terms of cell
      proliferation. Here, we used basic fibroblast growth factor (bFGF) in an alpha
      tricalcium phosphate cement with different initial powder sizes (coarse vs. fine;
      designated as CPC-C and CPC-F, respectively) and investigated the behavior of
      bFGF loading and release, as well as the effects on osteoblast responses. bFGF
      was loaded at 10 MUg/ml or 25 MUg/ml onto the set form of two types of CPCs,
      aiming to allow penetration into the pore structure and adsorption onto the
      cement crystallites. The CPC formulated with fine powder (CPC-F) had higher
      specific surface area and smaller-sized pores and retained slightly higher
      amounts of bFGF within the structure. The bFGF release study performed for 3
      weeks showed a sustained-release profile; after an initial rapid release over
      approximately 3 days, further release pattern was almost linear. Compared to CPC
      F, CPC-C showed a much faster release pattern. The effects of the bFGF
      incorporation within CPCs on cellular responses were assessed in terms of cell
      proliferation using MC3T3-E1 pre-osteoblastic cells. Compared with bFGF-free CPCs
      (both CPC-C and CPC-F), those containing bFGF stimulated cell proliferation for
      up to 7 days. An inhibition study of bFGF receptor demonstrated that the
      improvement of cell proliferation resulted from the role of bFGF released from
      the CPCs. This study provides beneficial information on improving the biological
      properties of CPCs by combining them with specific therapeutic molecules, and
      particularly with bFGF, showing that the cell proliferative ability was
      significantly stimulated, which may have potential applications for further use
      in stem cell-based bone tissue engineering.

PMID- 22962038
TI  - How can we improve accuracy of macroevolutionary rate estimates?

PMID- 22962039
TI  - Analysis of adipokine concentrations in paediatric non-alcoholic fatty liver
      disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver
      disease in children. It is important to distinguish children with more severe
      disease or steatohepatitis (NASH) from those with the less severe simple
      steatosis (SS) as prognosis differs. The importance of adipokines in the
      evolution of NASH is well recognized. OBJECTIVE: As adipokines are important in
      mediating inflammation, they may also be useful biomarkers of disease. METHODS:
      Plasma from 40 children (30 boys), median age 13.4 years, with liver biopsy
      proven NAFLD was analysed. Liver biopsies were scored using the NAFLD activity
      score and compared with adipokine concentrations. RESULTS: Median body mass index
      z-score was 2.12 with a median homeostasis model of assessment- insulin
      resistance of 4.08. Resistin was lower in NASH than in SS (P = 0.03). Monocyte
      chemoattractant protein 1 (MCP-1) was also lower in NASH (P = 0.04). MCP-1 was
      higher in children with severe fibrosis (P = 0.008) with an area under the
      receiver operating characteristic curve (AUROC) of 0.76. Plasminogen activator
      inhibitor 1 (PAI-1) was also higher in this group (P = 0.011) with an AUROC of
      0.78. There were no significant differences in leptin, adiponectin, adipsin,
      interleukin (IL) 6, IL10 or tumour necrosis factor alpha between groups.
      CONCLUSION: PAI-1 MCP-1 and resistin were differentially expressed with
      increasing severity of NAFLD. Though it is unlikely that this profile alone would
      serve as a biomarker of disease, differences found may contribute to
      understanding the role of these mediators in NAFLD.

PMID- 22962040
TI  - Homochiral crystallization of metal-organic silver frameworks: asymmetric [3+2]
      cycloaddition of an azomethine ylide.

PMID- 22962041
TI  - Calcium phosphate glass improves angiogenesis capacity of poly(lactic acid)
      scaffolds and stimulates differentiation of adipose tissue-derived mesenchymal
      stromal cells to the endothelial lineage.
AB  - The angiogenic capacity of a new biomaterial composite of poly(lactic acid) and
      calcium phosphate glass (PLA/CaP) was analyzed by noninvasive bioluminescence
      imaging (BLI) and histological procedures. Human adipose tissue-derived
      mesenchymal stromal cells expressing cytomegalovirus (CMV) promoter regulated
      Photinus pyralis luciferase (hAMSC-PLuc) grew up to 30 times the initial cell
      load, in vitro, when seeded in PLA/CaP scaffolds, but suffered an initial growth
      crisis followed by recovery when the scaffolds were subcutaneously implanted in
      SCID mice. To analyze changes in gene expression, hAMSC-PLuc cells were double
      labeled with a CMV promoter regulated Renilla reniformis luciferase and a
      Photinus pyralis luciferase reporter regulated by either the PECAM promoter or a
      hypoxia response element (HRE) artificial promoter and seeded in PLA/CaP and PLA
      scaffolds implanted in SCID mice. Analysis by BLI showed that hAMSCs in scaffolds
      were induced to differentiate to the endothelial lineage and did this faster in
      PLA/CaP than in PLA scaffolds. Endothelial differentiation correlated with a
      decrease in the activity of HRE regulated luciferase expression, indicative of a
      reduction of hypoxia. Histological analysis showed that PLA/CaP scaffolds were
      colonized by a functional host vascular system. Moreover, colonization by
      isolectin B(4) positive host cells was more effective in PLA/CaP than in PLA
      scaffolds, corroborating BLI results.

PMID- 22962043
TI  - Photostimulated and photosuppressed phase transitions in liquid crystals.

PMID- 22962042
TI  - Day-to-day physical functioning and disability in obese 10- to 13-year-olds.
AB  - What is already known about this subject? Compared with their healthy-weight
      peers, children with obesity have; impaired physical health-related quality of
      life reduced physical activity levels reduced capacity to perform certain weight
      bearing tasks in field-based fitness tests What this study adds? First
      investigation of obesity-related disability in children using the International
      Classification for Functioning, Disability and Health framework for Children and
      Youth. Obesity in children appears to be associated with disability impacting
      basic locomotor skills and physical health-related quality of life. Children's
      participation in key life areas related to physical functioning appears to be
      minimally impacted by obesity. OBJECTIVE: The aim of this study was to
      investigate whether obesity is related to impaired day-to-day physical
      functioning and disability in children. METHODS: An observational case-control
      study was conducted in three Australian states. Obese (n = 107) and healthy
      weight (n = 132) 10- to 13-year-olds (132 male, 107 female) were recruited via
      media advertisements. Assessment of body composition (dual energy X-ray
      absorptiometry), locomotor capacity (six-minute walk test [6MWT], timed up and
      down stairs test [TUDS] and timed up and go [TUG]) and child-reported physical
      health-related quality of life (HRQoL) were undertaken. Participants wore an
      accelerometer for 8 days and completed two use-of-time telephone interviews to
      assess participation in key life areas. RESULTS: Compared with their healthy
      weight counterparts, obese children had lower physical HRQoL scores (P < 0.01)
      and reduced locomotor capacity (TUDS z-score, TUG and 6MWT; P < 0.01). Higher
      percent body fat was significantly related to lower physical HRQoL scores (r = 
      0.48, P < 0.01), slower performance times for the TUDS and TUG (r = 0.59 and 0.26
      respectively, P < 0.01), shorter 6MWT distances (r = -0.51, P < 0.01) and reduced
      time spent in community participation activities (r = -0.23, P < 0.01).
      CONCLUSIONS: As anticipated, obesity appears to undermine physical functioning in
      children, including the capacity to perform basic locomotor skills yet,
      unexpectedly, participation in key life areas related to physical functioning
      appeared largely unaffected.

PMID- 22962044
TI  - Uterine artery embolization: a vascular surgery procedure? One vascular surgery
      group's experience.
AB  - Uterine artery embolization (UAE) has been performed by interventional radiology
      since the 1990s for symptomatic uterine fibroids with considerable success.
      Endovascular-trained vascular surgeons possess the necessary skills to
      successfully perform this procedure after an adequate but brief training period.
      Fourteen successful UAE procedures were performed by two vascular surgeons over a
      one-year period. Indications for the procedures were bleeding (12/14 patients,
      86%), pain/bloating/pressure (13/14 patients, 93%) and dyspareunia (2/14
      patients, 14%). All patients were initially evaluated by a gynecologist and
      referred for this procedure. Complications were minor and limited. Clinical
      follow-up demonstrated near-complete to complete symptom resolution in all but
      one patient for a 93% short-term success rate. Follow-up ultrasound studies
      demonstrated a reduction in the uterine fibroid size in all patients three months
      or more postprocedure. The mean fibroid size reduction was 4.07-3.26 cm (20%), P
      < 0.005. UAE is a procedure of proven benefit, well-matched to many vascular
      surgeons' skills and practice. Up to this point, few vascular surgeons have
      incorporated this endovascular procedure into their practices. This initial and
      somewhat limited study demonstrates one vascular surgery group's early success
      with this procedure.

PMID- 22962045
TI  - Aneurysmal degeneration of a saphenous vein graft following the repair of a
      popliteal aneurysm: case report and literature review.
AB  - True aneurysm formation in arterialized autologous veins is an unusual
      complication. A saccular aneurysmal degeneration of 53 mm (maximal diameter) of a
      saphenous vein graft inserted for repair of a popliteal aneurysm, four years
      after implantation, is reported. The patient (with prior history of abdominal
      aortic aneurysm) had been initially treated through a posterior approach. A new
      saphenous vein bypass grafting (medial approach) was performed. Histological
      examination revealed myointimal fibrosis, medial degeneration and inflammation.
      In spite of the widespread use of the autologous saphenous vein as an arterial
      substitute, this complication is extremely rare and its etiology remains unclear.
      Atherosclerosis is considered to be the main cause of aneurysm formation in vein
      grafts, but current data suggest that additional etiopathogenic factors should be
      further investigated. We note the rarity of this finding and review the
      literature for true aneurysm formation within vein grafts used for bypass
      procedures.

PMID- 22962046
TI  - Pulse wave velocity and the non-invasive methods used to assess it: Complior,
      SphygmoCor, Arteriograph and Vicorder.
AB  - Pulse wave velocity (PWV) is a known indicator of arterial stiffness and
      cardiovascular risk. We critically evaluated the evidence supporting the four
      main non-invasive devices available to assess it: Complior, SphygmoCor,
      Arteriograph and Vicorder. PubMed and Medline databases (1960-2011) were searched
      to identify studies reporting carotid-femoral PWV in humans using one or more of
      the four devices. Of the 183 articles retrieved, 43 met inclusion criteria. The
      Arteriograph device demonstrated least variance but had poor agreement with the
      other devices. Undisputable reference values for PWV need to be established and
      internationally agreed, and a standardized method for superficial distance
      measurement generated to reduce variability. Further studies comparing all four
      devices with invasive assessment are necessary.

PMID- 22962047
TI  - Vitamin D deficiency in children presenting to the emergency department: a
      growing concern. Vitamin D deficiency in Birmingham's children: presentation to
      the emergency department.
AB  - INTRODUCTION: The increase in detected vitamin D deficiency appears to be
      multifactorial: an increasingly multicultural society, reduced exposure to
      sunlight due to concern about skin cancer and a more sedentary lifestyle and
      dietary changes within the population. METHODS: This was a retrospective survey
      of children found to be vitamin D deficient after attending the emergency
      department from March 2009 until March 2010. These data were then subdivided
      according to their age, ethnic origin, presenting complaint and biochemical
      associated features. RESULTS: We identified 89 patients with a low vitamin D
      level (total vitamin D levels less than 50 nmol/l), with 83% of those having very
      low vitamin D levels (less than 25 nmol/l). The most common presenting features
      were abdominal pain (19%), a seizure (17%) and limb pain (15%). The most common
      ethnic origins in our series were Pakistani (37%) followed by black African
      (11.2%). CONCLUSIONS: Vitamin D deficiency should be considered in children with
      pigmented skin presenting with a range of symptoms. The detected vitamin D
      deficiency probably represents only a very small proportion of the vitamin D
      deficiency in children in Birmingham.

PMID- 22962048
TI  - Sensitive troponin assay predicts outcome in syncope.
AB  - AIMS: To assess whether plasma troponin concentration measured by a sensitive
      assay can predict 1-month and 1-year serious outcome, or all-cause death in
      patients presenting with syncope to the emergency department (ED). METHODS:
      Prospective cohort study of admitted adult patients presenting to the ED after an
      episode of syncope who had plasma troponin measured 12 h after syncope using the
      ARCHITECT STAT sensitive troponin I assay (Abbott Diagnostics). Primary endpoints
      were the composite endpoint of serious outcome or all-cause death at 1 month and
      1 year. RESULTS: Between 1 March 2007 and 22 July 2008, 338 of 528 patients
      admitted from the ED with syncope had plasma troponin concentrations determined.
      Troponin concentrations were above the limit of detection in 261 (77%) patients.
      Patients numbering 120 (36%) had a troponin concentration >=0.03 ng/ml (99th
      percentile of normal reference population), and 66 (20%) had concentrations
      >=0.05 ng/ml (local diagnostic threshold for myocardial infarction). The
      proportion of patients with a composite serious outcome increased across patients
      stratified into quintiles based on peak troponin concentration at 1 month (0%,
      9%, 13%, 26%, 70%) and at 1 year (10%, 22%, 26%, 52%, 85%). CONCLUSIONS: The
      majority of patients admitted from the ED with syncope have detectable plasma
      troponin concentrations. Peak troponin concentration was associated with
      increasing risk of serious outcome and death, and this risk increases with higher
      troponin concentrations. Troponin may have a future role in the risk
      stratification of patients with syncope.

PMID- 22962051
TI  - Massive traumatic subgaleal haematoma.

PMID- 22962049
TI  - Deliberate self-harm patients in the emergency department: who will repeat and
      who will not? Validation and development of clinical decision rules.
AB  - OBJECTIVES: (1) Validate an existing clinical tool for assessing risk after
      deliberate self-harm (DSH), Manchester Self-Harm Rule, in a new setting and new
      population, (2) develop a clinical decision rule based on factors associated with
      repeated self-harm in a Swedish population and (3) compare these rules. DESIGN: A
      consecutive series of 1524 patients attending one of Scandinavia's largest
      emergency departments (ED) due to DSH during a 3-year period were included.
      Explanatory factors were collected from hospital charts and national databases. A
      nationwide register-based follow-up of new DSH episode or death by suicide within
      6 months was used. We used logistic regression, area under the curve and
      classification trees to identify factors associated with repetition. To evaluate
      the ability of different decision rules to identify patients who will repeat DSH,
      we calculated the sensitivity and specificity. MAIN OUTCOME MEASURE: Repeated DSH
      or suicide within 6 months. RESULTS: The cumulative incidence for patients
      repeating within 6 months was 20.3% (95% CI 18.0% to 22.0%). Application of
      Manchester Self-Harm Rule to our material yielded a sensitivity of 89% and a
      specificity of 21%. The clinical decision rule based on four factors associated
      with repetition in the Swedish population yielded a sensitivity of 90% and a
      specificity of 18%. CONCLUSIONS: Application of either rules, with high
      sensitivity, may facilitate assessment in the ED and help focus right resources
      on patients at a higher risk. Irrespective of the choice of decision rule, it is
      difficult to separate those who will repeat from those who will not due to low
      specificity.

PMID- 22962052
TI  - A re-conceptualisation of acute spinal care.
AB  - The emergency care of patients who may have spinal injuries has become highly
      ritualised. There is little scientific support for many of the recommended
      interventions and there is evidence that at least some methods now used in the
      field and emergency department are harmful. Since prospective clinical trials are
      not likely to resolve these issues I propose a reconceptualisation of spinal
      trauma to allow a more rational approach to treatment. To do this I analyse the
      basic physics, biomechanics and physiology involved. I then develop a list of
      recommended treatment variations that are more in keeping with the actual causes
      of post impact neurological deterioration than are current methods. Discarding
      the fundamentally flawed emphasis on decreasing post injury motion and
      concentrating on efforts to minimise energy deposition to the injured site, while
      minimising treatment delays, can simplify and streamline care without subjecting
      patients to procedures that are not useful and potentially harmful. Specific
      treatments that are irrational and which can be safely discarded include the use
      of backboards for transportation, cervical collar use except in specific injury
      types, immobilisation of ambulatory patients on backboards, prolonged attempts to
      stabilise the spine during extrication, mechanical immobilisation of
      uncooperative or seizing patients and forceful in line stabilisation during
      airway management. 

PMID- 22962053
TI  - Are boys and girls that different? An analysis of traumatic brain injury in
      children.
AB  - INTRODUCTION: The Phillips Report on traumatic brain injury (TBI) in Ireland
      found that injury was more frequent in men and that gender differences were
      present in childhood. This study determined when gender differences emerge and
      examined the effect of gender on the mechanism of injury, injury type and
      severity and outcome. METHODS: A national prospective, observational study was
      conducted over a 2-year period. All patients under 17 years of age referred to a
      neurosurgical service following TBI were included. Data on patient demographics,
      events surrounding injury, injury type and severity, patient management and
      outcome were collected from 'on-call' logbooks and neurosurgical admissions
      records. RESULTS: 342 patients were included. Falls were the leading cause of
      injury for both sexes. Boys' injuries tended to involve greater energy transfer
      and involved more risk-prone behaviour resulting in a higher rate of other (non
      brain) injury and a higher mortality rate. Intentional injury occurred only in
      boys. While injury severity was similar for boys and girls, significant gender
      differences in injury type were present; extradural haematomas were significantly
      higher in boys (p=0.014) and subdural haematomas were significantly higher in
      girls (p=0.011). Mortality was 1.8% for girls and 4.3% for boys. CONCLUSIONS:
      Falls were responsible for most TBI, the home is the most common place of injury
      and non-operable TBI was common. These findings relate to all children.
      Significant gender differences exist from infancy. Boys sustained injuries
      associated with a greater energy transfer, were less likely to use protective
      devices and more likely to be injured deliberately. This results in a different
      pattern of injury, higher levels of associated injury and a higher mortality
      rate.

PMID- 22962054
TI  - Increase in prevalence of adiposity between the ages of 7 and 11 years reflects
      lower remission rates during this period.
AB  - What is already known about this subject? A considerable increase in the
      prevalence of overweight during the primary school years (7-11 years) has been
      reported. What this study adds? This reflects lower remission rates of excess
      body fat (i.e. the proportion of shifts from excess to normal body fat) between
      the ages of 7 and 11 years as compared with nearly balanced incidence and
      remission rates of excess body fat between the ages of 3 and 7 years. OBJECTIVE:
      This study aimed to compare the age-specific balance between incidence and
      remission of excess body fat between the ages of 3-7 and 7-11 years using the
      data from a longitudinal study. DESIGN: Longitudinal analysis based on the data
      from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD)
      Study, an ongoing, open cohort study in healthy children, conducted in Dortmund,
      Germany. Excess body fat was defined by the sum of triceps and subscapular skin
      fold measurements above the 90th reference percentile of the new German standard;
      overweight was defined using different national and international standards. The
      main outcome parameters were incidence and remission rates of excess body fat (n
      = 496) and overweight (n = 518) between the ages of 3 and 7 years and between the
      ages of 7 and 11 years. RESULTS: The incidence rates of excess skin-fold
      thickness between the ages of 3 and 7 years (4.2 [2.4, 6.2]%) and between the
      ages of 7 and 11 years (4.3 [2.6, 6.2]%) were almost identical. By contrast,
      remission rates were significantly lower during the age period of 7-11 years
      (primary school age) than during the age period of 3-7 years (pre-school age):
      37.5 (21.9, 53.1%) compared with 72.3 (59.6, 85.1%). CONCLUSIONS: These data
      point to the low remission of excess body fat as an important driving force for
      the increasing prevalence of excess body fat in children between the ages of 7
      and 11 years. Public health initiatives in children should encompass both primary
      prevention and interventions targeted at children already overweight at school
      entry.

PMID- 22962055
TI  - NHC-stabilized triorganozincates: syntheses, structures, and transformation to
      abnormal carbene-zinc complexes.

PMID- 22962056
TI  - Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer.
AB  - There is an immediate need for improved methods to systematically and precisely
      quantify large sets of peptides in complex biological samples. To date protein
      quantification in biological samples has been routinely performed on triple
      quadrupole instruments operated in selected reaction monitoring mode (SRM), and
      two major challenges remain. Firstly, the number of peptides to be included in
      one survey experiment needs to be increased to routinely reach several hundreds,
      and secondly, the degree of selectivity should be improved so as to reliably
      discriminate the targeted analytes from background interferences. High resolution
      and accurate mass (HR/AM) analysis on the recently developed Q-Exactive mass
      spectrometer can potentially address these issues. This instrument presents a
      unique configuration: it is constituted of an orbitrap mass analyzer equipped
      with a quadrupole mass filter as the front-end for precursor ion mass selection.
      This configuration enables new quantitative methods based on HR/AM measurements,
      including targeted analysis in MS mode (single ion monitoring) and in MS/MS mode
      (parallel reaction monitoring). The ability of the quadrupole to select a
      restricted m/z range allows one to overcome the dynamic range limitations
      associated with trapping devices, and the MS/MS mode provides an additional stage
      of selectivity. When applied to targeted protein quantification in urine samples
      and benchmarked with the reference SRM technique, the quadrupole-orbitrap
      instrument exhibits similar or better performance in terms of selectivity,
      dynamic range, and sensitivity. This high performance is further enhanced by
      leveraging the multiplexing capability of the instrument to design novel
      acquisition methods and apply them to large targeted proteomic studies for the
      first time, as demonstrated on 770 tryptic yeast peptides analyzed in one 60-min
      experiment. The increased quality of quadrupole-orbitrap data has the potential
      to improve existing protein quantification methods in complex samples and address
      the pressing demand of systems biology or biomarker evaluation studies.

PMID- 22962057
TI  - Understanding cullin-RING E3 biology through proteomics-based substrate
      identification.
AB  - Protein turnover through the ubiquitin-proteasome pathway controls numerous
      developmental decisions and biochemical processes in eukaryotes. Central to
      protein ubiquitylation are ubiquitin ligases, which provide specificity in
      targeted ubiquitylation. With more than 600 ubiquitin ligases encoded by the
      human genome, many of which remain to be studied, considerable effort is being
      placed on the development of methods for identifying substrates of specific
      ubiquitin ligases. In this review, we describe proteomic technologies for the
      identification of ubiquitin ligase targets, with a particular focus on members of
      the cullin-RING E3 class of ubiquitin ligases, which use F-box proteins as
      substrate specific adaptor proteins. Various proteomic methods are described and
      are compared with genetic approaches that are available. The continued
      development of such methods is likely to have a substantial impact on the
      ubiquitin-proteasome field.

PMID- 22962058
TI  - 10 best resources on ... pay for performance in low- and middle-income countries.

PMID- 22962060
TI  - Is there an app for that?

PMID- 22962059
TI  - The oncosurgery approach to managing liver metastases from colorectal cancer: a
      multidisciplinary international consensus.
AB  - An international panel of multidisciplinary experts convened to develop
      recommendations for the management of patients with liver metastases from
      colorectal cancer (CRC). The aim was to address the main issues facing the CRC
      hepatobiliary multidisciplinary team (MDT) when managing such patients and to
      standardize the treatment patients receive in different centers. Based on current
      evidence, the group agreed on a number of issues including the following: (a) the
      primary aim of treatment is achieving a long disease-free survival (DFS) interval
      following resection; (b) assessment of resectability should be performed with
      high-quality cross-sectional imaging, staging the liver with magnetic resonance
      imaging and/or abdominal computed tomography (CT), depending on local expertise,
      staging extrahepatic disease with thoracic and pelvic CT, and, in selected cases,
      fluorodeoxyglucose positron emission tomography with ultrasound (preferably
      contrast-enhanced ultrasound) for intraoperative staging; (c) optimal first-line
      chemotherapy-doublet or triplet chemotherapy regimens combined with targeted
      therapy-is advisable in potentially resectable patients; (d) in this situation,
      at least four courses of first-line chemotherapy should be given, with assessment
      of tumor response every 2 months; (e) response assessed by the Response
      Evaluation Criteria in Solid Tumors (conventional chemotherapy) or nonsize-based
      morphological changes (antiangiogenic agents) is clearly correlated with outcome;
      no imaging technique is currently able to accurately diagnose complete
      pathological response but high-quality imaging is crucial for patient management;
      (f) the duration of chemotherapy should be as short as possible and resection
      achieved as soon as technically possible in the absence of tumor progression; (g)
      the number of metastases or patient age should not be an absolute
      contraindication to surgery combined with chemotherapy; (h) for synchronous
      metastases, it is not advisable to undertake major hepatic surgery during surgery
      for removal of the primary CRC; the reverse surgical approach (liver first)
      produces as good an outcome as the conventional approach in selected cases; (i)
      for patients with resectable liver metastases from CRC, perioperative
      chemotherapy may be associated with a modestly better DFS outcome; and (j)
      whether initially resectable or unresectable, cure or at least a long survival
      duration is possible after complete resection of the metastases, and MDT
      treatment is essential for improving clinical and survival outcomes. The group
      proposed a new system to classify initial unresectability based on technical and
      oncological contraindications.

PMID- 22962061
TI  - Emotion unfolded by motion: a role for parietal lobe in decoding dynamic facial
      expressions.
AB  - Facial expressions convey important emotional and social information and are
      frequently applied in investigations of human affective processing. Dynamic faces
      may provide higher ecological validity to examine perceptual and cognitive
      processing of facial expressions. Higher order processing of emotional faces was
      addressed by varying the task and virtual face models systematically. Blood
      oxygenation level-dependent activation was assessed using functional magnetic
      resonance imaging in 20 healthy volunteers while viewing and evaluating either
      emotion or gender intensity of dynamic face stimuli. A general linear model
      analysis revealed that high valence activated a network of motion-responsive
      areas, indicating that visual motion areas support perceptual coding for the
      motion-based intensity of facial expressions. The comparison of emotion with
      gender discrimination task revealed increased activation of inferior parietal
      lobule, which highlights the involvement of parietal areas in processing of high
      level features of faces. Dynamic emotional stimuli may help to emphasize
      functions of the hypothesized 'extended' over the 'core' system for face
      processing. 

PMID- 22962062
TI  - Postnatal exposure history and airways: oxidant stress responses in airway
      explants.
AB  - Postnatally, the lung continues to grow and differentiate while interacting with
      the environment. Exposure to ozone (O(3)) and allergens during postnatal lung
      development alters structural elements of conducting airways, including
      innervation and neurokinin abundance. These changes have been linked with
      development of asthma in a rhesus monkey model. We hypothesized that O(3)
      exposure resets the ability of the airways to respond to oxidant stress and that
      this is mediated by changes in the neurokinin-1 receptor (NK-1R). Infant rhesus
      monkeys received episodic exposure to O(3) biweekly with or without house dust
      mite antigen (HDMA) from 6 to 12 months of age. Age-matched monkeys were exposed
      to filtered air (FA). Microdissected airway explants from midlevel airways
      (intrapulmonary generations 5-8) for four to six animals in each of four groups
      (FA, O(3), HDMA, and HDMA+O(3)) were tested for NK-1R gene responses to acute
      oxidant stress using exposure to hydrogen peroxide (1.2 mM), a lipid ozonide (10
      MUM), or sham treatment for 4 hours in vitro. Airway responses were measured
      using real-time quantitative RT-PCR of NK-1R and IL-8 gene expression. Basal NK
      1R gene expression levels were not different between the exposure groups.
      Treatment with ozonide or hydrogen peroxide did not change NK-1R gene expression
      in animals exposed to FA, HDMA, or HDMA+O(3). However, treatment in vitro with
      lipid ozonide significantly increased NK-1R gene expression in explants from O(3)
      exposed animals. We conclude that a history of prior O(3) exposure resets the
      steady state of the airways to increase the NK-1R response to subsequent acute
      oxidant stresses.

PMID- 22962063
TI  - In utero exposure to second-hand smoke aggravates adult responses to irritants:
      adult second-hand smoke.
AB  - In utero exposure to second-hand smoke (SHS) is associated with exacerbated
      asthmatic responses in children. We tested the hypothesis that in utero SHS will
      aggravate the lung responses of young adult mice re-exposed to SHS. We exposed
      Balb/c mice in utero to SHS (S) or filtered air (AIR; A), and re-exposed the male
      offspring daily from 11-15 weeks of age to either SHS (AS and SS) or AIR (AA and
      SA). After the adult exposures, we analyzed samples of bronchoalveolar lavage
      fluid (BALF), examined the results of histopathology, and assessed pulmonary
      function and gene expression changes in lung samples. In SS mice, compared with
      the other three groups (AA, AS, and SA), we found decreases in breathing
      frequency and increases in airway hyperresponsiveness (AHR), as well as low but
      significantly elevated concentrations of BALF proinflammatory cytokines (IL-1b,
      IL-6, and keratinocyte-derived chemokine). Lung morphometric analyses revealed
      enlarged airspaces and arteries in SA and SS mice compared with their in utero
      AIR counterparts, as well as increased collagen deposition in AS and SS mice.
      Unique gene expression profiles were found for in utero, adult, and combined
      exposures, as well as for mice with elevated AHR responses. The profibrotic
      metalloprotease genes, Adamts9 and Mmp3, were up-regulated in the SS and AHR
      groups, suggesting a role for in utero SHS exposure on the adult development of
      chronic obstructive pulmonary disease. Our results indicate that in utero
      exposures to environmentally relevant concentrations of SHS alter lung structure
      more severely than do adult SHS exposures of longer duration. These in utero
      exposures also aggravate AHR and promote a profibrotic milieu in adult lungs.

PMID- 22962064
TI  - Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell
      responses and inhibits allergic airway eosinophilia.
AB  - Toll-like receptor (TLR) agonists beneficially modulate allergic airway
      inflammation. However, the efficiency of TLR agonists varies considerably, and
      their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely
      understood. We investigated at a cellular level whether the administration of the
      pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R
      cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic
      peptide (BPP-OVA) could divert an existing Th2 response and influence airway
      eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a
      classic murine sensitization/challenge model and an adoptive transfer model,
      which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)
      specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs)
      was determined both in vitro and in vivo, combined with a cytokine secretion
      analysis. A single mucosal application of BPP-OVA efficiently delivered antigen,
      led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell
      proliferation via lung DCs in vivo. In alternative models of allergic airway
      disease, a single administration of BPP-OVA before OVA challenge (but not BPP
      alone) significantly reduced airway eosinophilia, most likely through altered
      antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred
      Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA
      guides antigen-specific Th2 cells to produce significantly higher amounts of IFN
      gamma upon allergen challenge. In conclusion, our data show for the first time
      that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can
      provoke IFN-gamma responses in Th2-biased cells and alleviate allergic airway
      inflammation.

PMID- 22962065
TI  - Adenoviral gene transfer of endothelin-1 in the lung induces pulmonary fibrosis
      through the activation of focal adhesion kinase.
AB  - Endothelin-1 (ET-1) has been implicated in the development of pulmonary fibrosis,
      based on its capacity in vitro to promote extracellular matrix (ECM) production
      and contraction, and on studies showing elevated expression of ET-1 and its
      receptors in patients with pulmonary fibrosis. However, the in vivo fibrogenic
      effect of ET-1 is not well characterized. We used the adenoviral-mediated gene
      transfer of ET-1 to overexpress ET-1 transiently in murine lungs by intratracheal
      administration. An increased expression of ET-1 for 3 to 10 days after injection
      resulted in a moderate but reversible fibrotic response, peaking on Day 14 after
      infection and characterized by the deposition of ECM components, myofibroblast
      formation, and a significant inflammatory infiltrate, mainly in the
      peribronchiolar/perivascular region. Adenoviral-mediated ET-1 overexpression
      activated focal adhesion kinase (FAK) both in vitro, using primary murine lung
      fibroblasts, and in vivo, intratracheally administered in the lungs of mice. The
      inhibition of FAK with the compound PF-562,271 prevented ET-1-mediated collagen
      deposition and myofibroblast formation, thereby preventing the development of
      lung fibrosis. In conclusion, we demonstrate that the overexpression of ET-1
      directly in the lungs of mice can initiate a fibrogenic response characterized by
      increased ECM deposition and myofibroblast formation, and that this effect of ET
      1 can be prevented by inhibition of FAK. Our data suggest that the ET-1/FAK axis
      may contribute importantly to the pathogenesis of fibrotic disorders, and
      highlight FAK as a potential therapeutic target in these devastating diseases.

PMID- 22962066
TI  - Hyperthermia promotes and prevents respiratory epithelial apoptosis through
      distinct mechanisms.
AB  - Hyperthermia has been shown to confer cytoprotection and to augment apoptosis in
      different experimental models. We analyzed the mechanisms of both effects in the
      same mouse lung epithelial (MLE) cell line (MLE15). Exposing MLE15 cells to heat
      shock (HS; 42 degrees C, 2 h) or febrile-range hyperthermia (39.5 degrees C)
      concurrent with activation of the death receptors, TNF receptor 1 or Fas, greatly
      accelerated apoptosis, which was detectable within 30 minutes and was associated
      with accelerated activation of caspase-2, -8, and -10, and the proapoptotic
      protein, Bcl2-interacting domain (Bid). Caspase-3 activation and cell death were
      partially blocked by inhibitors targeting all three initiator caspases. Cells
      expressing the IkappaB superrepessor were more susceptible than wild-type cells
      to TNF-alpha-induced apoptosis at 37 degrees C, but HS and febrile-range
      hyperthermia still increased apoptosis in these cells. Delaying HS for 3 hours
      after TNF-alpha treatment abrogated its proapoptotic effect in wild-type cells,
      but not in IkappaB superrepressor-expression cells, suggesting that TNF-alpha
      stimulates delayed resistance to the proapoptotic effects of HS through an NF
      kappaB-dependent mechanism. Pre-exposure to 2-hour HS beginning 6 to16 hours
      before TNF-alpha treatment or Fas activation reduced apoptosis in MLE15 cells.
      The antiapoptotic effects of HS pretreatment were reduced in TNF-alpha-treated
      embryonic fibroblasts from heat shock factor-1 (HSF1)-deficient mice, but the
      proapoptotic effects of concurrent HS were preserved. Thus, depending on the
      temperature and timing relative to death receptor activation, hyperthermia can
      exert pro- and antiapoptotic effects through distinct mechanisms.

PMID- 22962067
TI  - Availability and night-time use of electronic entertainment and communication
      devices are associated with short sleep duration and obesity among Canadian
      children.
AB  - What is already known about this subject Short sleep duration is a risk factor
      for obesity. Television (TV) in the bedroom has been shown to be associated with
      excess body weight in children. Children increasingly use other electronic
      entertainment and communication devices (EECDs) such as video games, computers,
      and smart phones. What this study adds Access to and night-time use of EECDs are
      associated with shortened sleep duration, excess body weight, poorer diet
      quality, and lower physical activity levels. Our findings reinforce existing
      recommendations pertaining to TV and Internet access by the American Academy of
      Pediatrics and suggest to have these expanded to restricted availability of video
      games and smart phones in children's bedrooms. BACKGROUND: While the prevalence
      of childhood obesity and access to and use of electronic entertainment and
      communication devices (EECDs) have increased in the past decades, no earlier
      study has examined their interrelationship. OBJECTIVE: To examine whether night
      time access to and use of EECDs are associated with sleep duration, body weights,
      diet quality, and physical activity of Canadian children. METHODS: A
      representative sample of 3398 grade 5 children in Alberta, Canada, was surveyed.
      The survey included questions on children's lifestyles and health behaviours, the
      Harvard Youth/Adolescent Food Frequency questionnaire, a validated questionnaire
      on physical activity, and measurements of heights and weights. Random effect
      models were used to assess the associations of night-time access to and use of
      EECDs with sleep, diet quality, physical activity, and body weights. RESULTS:
      Sixty-four percent of parents reported that their child had access to one or more
      EECDs in their bedroom. Access to and night-time use of EECDs were associated
      with shortened sleep duration, excess body weight, poorer diet quality, and lower
      physical activity levels in a statistically significant manner. CONCLUSIONS:
      Limiting the availability of EECDs in children's bedrooms and discouraging their
      night-time use may be considered as a strategy to promote sleep and reduce
      childhood obesity.

PMID- 22962068
TI  - Sexual dimorphism and human enhancement.
AB  - Robert Sparrow argues that because of women's longer life expectancy philosophers
      who advocate the genetic modification of human beings to enhance welfare rather
      than merely supply therapy are committed to favouring the selection of only
      female embryos, an implication he deems sufficiently implausible to discredit
      their position. If Sparrow's argument succeeds, then philosophers who advocate
      biomedical moral enhancement also seem vulnerable to a similar charge because of
      men's greater propensity for various forms of harmful wrongdoing. This paper
      argues there are various flaws in Sparrow's argument that render it unsuccessful.
      The paper also examines whether dimorphism reduction is a more desirable outcome
      than male elimination, thereby further illustrating the difficulties besetting
      the distinction between therapy and enhancement. 

PMID- 22962069
TI  - Association of water softness and heavy alcohol consumption with higher hospital
      admission rates for alcoholic liver disease.
AB  - AIMS: To test the hypothesis that regional variations in the prevalence of
      alcoholic liver disease are contributed to by regional variations in 'softness'
      of drinking water, i.e. its mineral content. METHODS: Annual hospital admission
      rates for alcoholic liver disease per 100,000 population in the 28 Strategic
      Health Authorities (SHAs) existing in England over the period 2003-2006 were
      compared with regional measures of water hardness, alcohol consumption and social
      deprivation. As corroborative evidence, the same relations were examined for
      hospital admission rates for osteoporosis, a disorder with an already established
      link with calcium deficiency in drinking water (as well as with heavy drinking).
      RESULTS: Hospital admissions rates for alcoholic liver disease were higher in
      predominant-soft-water SHAs than with hard water SHAs. These areas, with one
      exception, were also associated with high alcohol consumption, but not with
      greater social deprivation. Hospital admission rates for osteoporosis were found
      to vary in a way similar to that for alcoholic liver disease, with significant
      correlations with soft water and alcohol consumption. CONCLUSION: Given
      experimental evidence that magnesium deficiency can aggravate liver damage from
      alcohol, soft water with its low magnesium concentration may be a factor
      additional to alcohol consumption in the development of liver damage. The
      parallel findings with osteoporosis admissions, explainable by low calcium and
      magnesium levels present in soft water, along with the known effect of heavy
      drinking on bone metabolism, provide corollary support for the hypothesis linking
      soft water with the pathogenesis of these two diseases.

PMID- 22962070
TI  - Changes in high-risk sexual behaviour among Estonian adults between 1996 and
      2006.
AB  - OBJECTIVE: To describe and compare sexual behaviour patterns in 1996 (before the
      explosion of the HIV epidemic in 2000) and 2006, and the correlates of high-risk
      sexual behaviour in Estonia. METHODS: Data on selected sexual behaviour
      characteristics were obtained by interviewing a probability sample of the adult
      population in Estonia in 1996 and 2006. RESULTS: Data were available from 2441
      sexually experienced women and 1994 men, and 3005 women and 2812 men in the year
      2006. There were no changes in the proportion of sexually experienced adults,
      frequency of intercourse, or same gender sexual relationships. There was an
      increase in sex under the age of 16 (women: 8.4% vs 14.1% adjusted OR (AOR) 2.05
      (1.67 to 2.53); men: 21.9% vs 28.0% AOR 1.58 (1.35 to 1.84)). From 1996 to 2006,
      the proportion reporting intercourse with a casual partner in the previous 12
      months decreased significantly for women (10.7% vs 6.0% AOR 0.54 (95% CI 0.41 to
      0.72)) and men, (24.0% vs 16.5% AOR 0.71 (0.59 to 0.85)) in parallel with a
      decrease in those reporting never using condoms during intercourse with a casual
      partner (for women: 49.3% vs 19.2% AOR 0.27 (0.14 to 0.51); and men: 35.4% vs
      20.2% AOR 0.37 (0.25 to 0.56)). In 2006, the odds for not always using condoms in
      intercourse with casual partners increased significantly with age (eg, <= 24 vs
      >= 45: AOR 3.46 (1.68 to 7.13)), and were higher among those
      widowed/divorced/separated (AOR 2.35 (CI 1.20 to 4.60)). CONCLUSIONS: From 1996
      to 2006, a significant reduction in high-risk sexual behaviour has occurred in
      Estonia across all age groups and genders.

PMID- 22962091
TI  - Mid-regional pro-adrenomedullin improves disposition strategies for patients with
      acute dyspnoea: results from the BACH trial.
AB  - OBJECTIVES: To assess the value of mid-regional pro-adrenomedullin (MR-proADM) in
      guiding patient disposition from the emergency department (ED), as one of the key
      factors of hospital resource utilisation, in undifferentiated patients with acute
      dyspnoea. METHODS: We used clinical and outcome data from a large international
      biomarker study (BACH trial) and analysed data of all 1557 patients of the
      European and US sites presenting with acute dyspnoea. Patients were discharged or
      transferred from the ED to different levels of care (general ward, monitoring
      unit, intensive care unit). This original patient disposition was compared with
      the hypothetical disposition based on an adapted method of net reclassification
      improvement (NRI), which upgraded or downgraded patients from one level of care
      to the other based on the MR-proADM test result. RESULTS: MR-pro-ADM was
      significantly higher in patients who died during the follow-up than in survivors
      (p<0.0001). When applying the adapted NRI model, 30 additional patients from the
      European Union (EU) and 55 additional patients from USA were theoretically
      discharged (increase of 16.5%) if MR-proADM had been used for patient management.
      The overall NRI, adding up the rates of upgrades and downgrades, in the EU was
      16.0% (95% CI 8.2% to 23.9%). A total of n=72 (9.9%) patients changed disposition
      when adding MR-pro ADM. In the USA, the overall NRI was 12.0% (5.7%-18.4%) and a
      total of n=81 (11.2%) patients changed disposition. CONCLUSIONS: MR-proADM has
      the potential to guide initial disposition of undifferentiated ED patients with
      acute dyspnoea and might therefore be helpful to improve resource utilisation and
      patient care.

PMID- 22962092
TI  - Improving safety and efficiency during emergent central venous catheter placement
      with a needleless securing clamp.
AB  - OBJECTIVE: To compare the needleless securing clamp to the traditional suture
      secured clamp for central venous catheters. METHODS: Compare the holding strength
      of each type of clamps by measuring the amount of kinetic energy absorbed, ask 20
      physicians to evaluate the clamp placement using sutures or staples, and
      summarise the clamps effectiveness and complications in 10 patients. RESULTS:
      Compared to sutured clamp, the needleless clamp was more secure. The needleless
      clamp was also significantly better with regard to ease of use, safety, perceived
      strength (p value <0.002), and insertion time was reduced by 63%. No adverse
      events or skin infections occurred while using the needleless clamps.
      CONCLUSIONS: Without incurring complications or increasing risk to patients, the
      needleless clamp is secure and improves safety and efficiency for physicians.

PMID- 22962093
TI  - "A good death"--sequence (not stigma), to an enigma called life: case report on
      end-of-life decision making and care.
AB  - Fear of death and the stigma associated with the terminal events of illness
      prevents us from dying well. Lack of recognition of palliative care as a
      speciality, in many countries, leads us to die a pathetic death in ICU rather
      than dying at home with near and dear ones around. Its time to break the taboo of
      death and to start talking about this terminal sequence (good death) of good
      living. 

PMID- 22962094
TI  - Legal drug content in music video programs shown on Australian television on
      saturday mornings.
AB  - AIMS: To examine the extent to which legal drug references (alcohol and tobacco)
      are present in the music video clips shown on two music video programs broadcast
      in Australia on Saturday mornings. Further, to examine the music genres in which
      the references appeared and the dominant messages associated with the references.
      METHODS: Music video clips shown on the music video programs 'Rage' (ABC TV) and
      [V] 'Music Video Chart' (Channel [V]) were viewed over 8 weeks from August 2011
      to October 2011 and the number of clips containing verbal and/or visual drug
      references in each program was counted. The songs were classified by genre and
      the dominant messages associated with drug references were also classified and
      analysed. RESULTS: A considerable proportion of music videos (approximately one
      third) contained drug references. Alcohol featured in 95% of the music videos
      that contained drug references. References to alcohol generally associated it
      with fun and humour, and alcohol and tobacco were both overwhelmingly presented
      in contexts that encouraged, rather than discouraged, their use. CONCLUSION: In
      Australia, Saturday morning is generally considered a children's television
      viewing timeslot, and several broadcaster Codes of Practice dictate that programs
      shown on Saturday mornings must be appropriate for viewing by audiences of all
      ages. Despite this, our findings show that music video programs aired on Saturday
      mornings contain a considerable level of drug-related content.

PMID- 22962194
TI  - Chart biopsy: an emerging medical practice enabled by electronic health records
      and its impacts on emergency department-inpatient admission handoffs.
AB  - OBJECTIVE: To examine how clinicians on the receiving end of admission handoffs
      use electronic health records (EHRs) in preparation for those handoffs and to
      identify the kinds of impacts such usage may have. MATERIALS AND METHODS: This
      analysis is part of a two-year ethnographic study of emergency department (ED) to
      internal medicine admission handoffs at a tertiary teaching and referral
      hospital. Qualitative data were gathered and analyzed iteratively, following a
      grounded theory methodology. Data collection methods included semi-structured
      interviews (N = 48), observations (349 hours), and recording of handoff
      conversations (N = 48). Data analyses involved coding, memo writing, and member
      checking. RESULTS: The use of EHRs has enabled an emerging practice that we refer
      to as pre-handoff "chart biopsy": the activity of selectively examining portions
      of a patient's health record to gather specific data or information about that
      patient or to get a broader sense of the patient and the care that patient has
      received. Three functions of chart biopsy are identified: getting an overview of
      the patient; preparing for handoff and subsequent care; and defending against
      potential biases. Chart biopsies appear to impact important clinical and
      organizational processes. Among these are the nature and quality of handoff
      interactions, and the quality of care, including the appropriateness of
      dispositioning of patients. CONCLUSIONS: Chart biopsy has the potential to enrich
      collaboration and to enable the hospital to act safely, efficiently, and
      effectively. Implications for handoff research and for the design and evaluation
      of EHRs are also discussed.

PMID- 22962195
TI  - The future state of clinical data capture and documentation: a report from AMIA's
      2011 Policy Meeting.
AB  - Much of what is currently documented in the electronic health record is in
      response toincreasingly complex and prescriptive medicolegal, reimbursement, and
      regulatory requirements. These requirements often result in redundant data
      capture and cumbersome documentation processes. AMIA's 2011 Health Policy Meeting
      examined key issues in this arena and envisioned changes to help move toward an
      ideal future state of clinical data capture and documentation. The consensus of
      the meeting was that, in the move to a technology-enabled healthcare environment,
      the main purpose of documentation should be to support patient care and improved
      outcomes for individuals and populations and that documentation for other
      purposes should be generated as a byproduct of care delivery. This paper
      summarizes meeting deliberations, and highlights policy recommendations and
      research priorities. The authors recommend development of a national strategy to
      review and amend public policies to better support technology-enabled data
      capture and documentation practices.

PMID- 22962197
TI  - Nanoparticles in the environment: stability and toxicity.
AB  - With the increasing use and application of engineered nanoparticles (ENPs) in a
      number industries, ENPs, through their unique properties, have made their way
      into the environment. However, the environmental fate and behavior of ENPs are
      largely unknown. Laboratory studies have shown that some ENPs have the potential
      for toxicity, suggesting they may affect organisms in the environment. To fully
      assess the risk of ENPs, a better estimation of exposure concentrations is
      needed. This requires an understanding of the stability and toxicity of
      nanoparticles (NPs) in the environment. This review presents a brief overview of
      the fate, behavior, and ecotoxicity of NPs in the environment. The fate and
      transport of NPs, which can be affected by various environmental conditions like
      light, pH, ionic strength, and type and concentration of cations, are important
      for the examination of the life cycle of NPs.

PMID- 22962196
TI  - Arsenic and human health: epidemiologic progress and public health implications.
AB  - Elevated concentrations of arsenic in groundwater pose a public health threat to
      millions of people worldwide, including severely affected populations in South
      and Southeast Asia. Although arsenic is an established human carcinogen and has
      been associated with a multitude of health outcomes in epidemiologic studies, a
      mode of action has yet to be determined for some aspects of arsenic toxicity.
      Herein, we emphasize the role of recent genetic and molecular epidemiologic
      investigations of arsenic toxicity. Additionally, we discuss considerations for
      the public health impacts of arsenic exposure through drinking water with respect
      to primary and secondary prevention efforts.

PMID- 22962199
TI  - Support for Project P.A.T.H.S. in Hong Kong: continuation of positive evaluation
      evidence.

PMID- 22962200
TI  - From experienced to novice: a reflective account on the changing role of front
      line implementer to program trainer in Project P.A.T.H.S.
AB  - Although training plays an important role in the successful implementation of
      positive youth development programs, research on training and trainers in this
      field is grossly neglected. In this paper, a trainer of a positive youth
      development program in Hong Kong (Project P.A.T.H.S.; Positive Adolescent
      Training through Holistic Social Programmes) reflected about her transition from
      the role of a teacher (and program implementer) to the role of a trainer. Based
      on the reflection, the transformations involved, including self-perception,
      teaching role and teaching strategies, were highlighted. The issue of how
      previous experience influenced training in the context of positive youth
      development was also discussed. It is suggested that involvement of front-line
      practitioners in the training of positive youth development programs is workable,
      although systematic training for the novice trainers may be needed.

PMID- 22962201
TI  - The role of program, people, process, policy and place (5Ps) in the
      implementation of a positive youth development program.
AB  - There is scant literature about identifying factors contributing to the success
      of the implementation of programs to help understand the interrelationships among
      multiple facets of implementation. In this paper, a front-line implementer
      reviewed the execution practice of Project P.A.T.H.S. (Positive Adolescent
      Training through Holistic Social Programmes) in her former school in terms of
      program, people, process, policy and place (5Ps). By examining the factors
      contributing to the success of the implementation, the authors intend to fill the
      gap between the research and the practical school-based front-line
      implementation. Although the program implementation process was examined in
      researchers' "expert" perspective, it would be helpful if more research employed
      front-line workers as collaborators and participants in the implementation
      process to understand what actually happen in the program implementation process.

PMID- 22962202
TI  - Interim evaluation of the Tier 1 Program of Project P.A.T.H.S.: continuation of
      evidence.
AB  - An interim evaluation study was conducted to understand the implementation of the
      Tier 1 Program of Project P.A.T.H.S. (Positive Adolescent Training through
      Holistic Social Programmes) in the 2008/09 school year. One hundred and twenty
      eight schools were randomly selected to provide information on the implementation
      details of the program via interviews, telephone interviews and self-completed
      questionnaires. Results showed that a majority of the workers perceived that the
      students had positive responses to the program and the program was helpful to the
      students. Program workers' views toward the implementation of the Tier 1 Program
      were positive across different grades and program implementation modes. In
      conjunction with previous studies, the present findings suggest that the Tier 1
      Program of Project P.A.T.H.S. is well received by different stakeholders.

PMID- 22962203
TI  - Program implementers' evaluation of Project P.A.T.H.S. in Hong Kong: a study
      based on different cohorts.
AB  - A total of 216 schools participated in the Tier 1 Program (Secondary 1, 2 and 3
      levels) of Project P.A.T.H.S. (Positive Adolescent Training through Holistic
      Social Programmes) in the 2008/09 school year. Based on the subjective outcome
      evaluation findings collected from students and instructors in each grade, the
      program implementers wrote down five conclusions in their reports. Utilizing
      secondary data analysis, the conclusions in the reports were further analyzed.
      Results showed that most of the conclusions concerning perceptions of the
      program, instructors and effectiveness of the program were positive in nature.
      There were also conclusions indicating difficulties encountered and
      recommendations for improvement. The result of the present study is consistent
      with previous studies using the same method as well as using other evaluation
      means for the same grades. The findings suggest that the Tier 1 Program is well
      received by the stakeholders and the program is effective in promoting the
      holistic development of adolescents.

PMID- 22962204
TI  - A stakeholder-collaborative evaluation of intervention for students with greater
      psychosocial needs.
AB  - The Tier 2 Program of Project P.A.T.H.S. (Positive Adolescent Training through
      Holistic Social Programmes) in Hong Kong was designed and implemented by school
      social workers targeting adolescents with greater psychosocial needs. Based on
      the responses of 237 participants, 48 program implementers wrote down five
      conclusions on the program effectiveness in their reports submitted to the
      funding body. Based on a stakeholder-collaborative approach involving secondary
      data analyses, results showed that most conclusions were positive regarding
      participants' perceptions of the program, instructors and their perceived program
      effectiveness, although there were also conclusions reflecting difficulties
      encountered and suggestions for improvements. In conjunction with the previous
      evaluation findings, the present study suggests that the Tier 2 Program was well
      received by the stakeholders and the program was beneficial to the development of
      the program participants.

PMID- 22962205
TI  - Impact of Project P.A.T.H.S. on adolescent developmental outcomes in Hong Kong:
      findings based on seven waves of data.
AB  - The present study examined the longitudinal impact of Project P.A.T.H.S.
      (Positive Adolescent Training through Holistic Social Programmes) on adolescent
      developmental outcomes in Hong Kong. Using a longitudinal randomized group
      design, seven waves of data were collected from 24 experimental schools (n=4049
      at wave 1) in which students participated in the Tier 1 Program of Project
      P.A.T.H.S. and 24 control schools (n=3797 at wave 1). Results based on individual
      growth curve modeling generally showed that, relative to the control
      participants, participants in the experimental group had: (a) a higher level of
      positive development; (b) a lower level of substance abuse; and (c) a lower level
      of delinquent behavior. Participants who regarded the program to be beneficial
      also showed higher levels of positive development and lower levels of problem
      behavior than did the control school students. The present findings suggest that
      Project P.A.T.H.S. is effective in promoting positive development and preventing
      adolescent problem behavior in Chinese adolescents in Hong Kong.

PMID- 22962206
TI  - Qualitative evaluation of Project P.A.T.H.S. in Hong Kong: focus groups based on
      Secondary 3 program implementers.
AB  - Ten focus groups comprising 42 program implementers recruited from 10 schools
      were conducted to evaluate the Tier 1 Program (Secondary 3) of Project P.A.T.H.S.
      (Positive Adolescent Training through Holistic Social Programs) in the 2008/09
      school year. Results showed that a majority of the program implementers used
      positive descriptors and metaphors to represent the program and they perceived
      that the program benefited the program participants in various psychosocial
      domains. In conjunction with the previous research findings, the present study
      provides further support for the effectiveness of the Tier 1 Program of Project
      P.A.T.H.S.

PMID- 22962207
TI  - Implementation of the Secondary 2 Program of Project P.A.T.H.S.: observations
      based on the co-walker scheme.
AB  - The present study examined the implementation quality of the Tier 1 Program of
      Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social
      Programmes) at Secondary 2 level in the third year of the initial phase of the
      project in Hong Kong. Classroom observations of 222 units in 148 schools were
      conducted under the co-walker scheme. Results generally showed that the overall
      level of program adherence was high and different dimensions of program delivery
      were positively correlated amongst themselves. Instructors' use of positive and
      supportive feedback, degree of achievement of the objectives, and lesson
      preparation significantly predicted both the overall implementation quality and
      perceived success of the program. While instructors' interactive delivery method
      and their familiarity with the students predicted overall implementation quality,
      student participation and involvement, and opportunity for reflection were
      predictive of implementation success. In conjunction with other evaluation
      findings, the present study lends further support to the high implementation
      quality of Project P.A.T.H.S. in Hong Kong.

PMID- 22962208
TI  - Implementation of the Secondary 3 Program of Project P.A.T.H.S.: observations
      based on the co-walker scheme.
AB  - The present study was conducted to explore the implementation quality of the
      Secondary 3 Program of the Tier 1 Program of Project P.A.T.H.S. (Positive
      Adolescent Training through Holistic Social Programmes) in the third year of the
      Full Implementation Phase. Classroom observations of 182 units in 129 schools
      were conducted. Results showed that the overall level of program adherence was
      73.9%. Thirteen aspects concerning program delivery were significantly
      correlated. Multiple regression analyses revealed that overall implementation
      quality was significantly predicted by student participation and involvement,
      strategies to enhance student motivation, use of positive and supportive
      feedback, degree of achievement of the objectives, and lesson preparation.
      Success of implementation was significantly predicted by student participation
      and involvement, classroom control, use of positive and supportive feedback,
      opportunity for reflection, degree of achievement of the objectives and time
      management. The present findings generally suggest that the implementation
      quality of Project P.A.T.H.S. was high.

PMID- 22962209
TI  - Quantitative evaluation of the revised training program Project P.A.T.H.S. in
      Hong Kong.
AB  - In the extension phase of Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) in Hong Kong, potential implementers received
      20 h of training (7 h of e-learning and 13 h of interactive training). Subjective
      outcome evaluation was conducted to evaluate the training workshops conducted in
      the first year of the extension phase based on the responses of 812 participants.
      The subjective outcome evaluation form was found to be internally consistent.
      Percentage findings showed that the respondents had favorable perceptions of the
      training program including its content, trainers, participants themselves and
      arrangements. The participants also felt that they had acquired knowledge,
      positive attitudes and skills related to the implementation of the program. The
      findings showed that the revised training program was effective in helping the
      participants to acquire the necessary knowledge, attitudes, and skills in the
      implementation of the program.

PMID- 22962210
TI  - Implementation of a positive youth development program by class teachers in a
      Chinese context.
AB  - This paper reports the findings of a case study in which a curriculum-based
      positive youth development program (Project P.A.T.H.S.) was implemented by the
      class teachers in a school. School-related factors which contributed to the
      success of program implementation were identified in the study. Results showed
      that factors facilitating the program implementation were closely related to the
      "5Ps" model (i.e., program, people, process, policy and place). While all the
      above factors contributed to the success of program implementation, the "people"
      factor was identified as the most crucial factor. Overall, both the students and
      program implementers perceived the program to be effective in promoting holistic
      development in the program participants.

PMID- 22962211
TI  - Genomic advances for gene discovery in hereditary hearing loss.
AB  - High-throughput sequencing is changing the face of genetic diagnosis and
      counseling. While in the past, it would take on average 1 to 5 years to identify
      a mutation leading to deafness, today, the genetic basis for deafness can be
      determined within months in a child or adult with inherited hearing loss.
      Obstacles and challenges still remain, but the field is changing at a dramatic
      rate, making gene discovery a much easier and more efficient task than in the
      past.

PMID- 22962212
TI  - No changes in cochlear implant mapping and audiometric parameters in adolescence.
AB  - BACKGROUND: Audiologists mapping in the clinic report that many cochlear
      implanted teenagers and their parents complain of deterioration in hearing
      capabilities. The aim of this study was to compare the mapping parameters
      measured over the years and determine whether more changes occurred throughout
      adolescence than during childhood. METHODS: The files of 23 cochlear-implanted
      teenagers were studied retrospectively. Data were collected for each individual
      at several time points between the ages of 6.5 and 18.25 years. Typical data
      collected from the mapping sessions included behaviorally measured T values,
      impedance results, audiogram thresholds in the free field with the implant,
      speech reception threshold, and speech perception of vowel-consonant-vowel
      syllables. RESULTS: No changes were found in either the behavioral or the
      objective parameters over the years. CONCLUSIONS: The stability in mapping and
      audiometric measurements found in adolescence do not support an explanation based
      on hormonal and growth effects on implant function. Perhaps a more likely cause
      of the subjective sense of hearing deterioration is related to changes in social
      and educational requirements.

PMID- 22962213
TI  - Evaluation of NGAL TestTM, a fully-automated neutrophil gelatinase-associated
      lipocalin (NGAL) immunoassay on Beckman Coulter AU 5822.
AB  - BACKGROUND: The neutrophil gelatinase associated lipocalin (NGAL) has been
      identified as the most promising biomarker of acute kidney injury (AKI). This
      study was aimed to evaluate a NGAL immunoassay on Beckman Coulter AU 5822.
      METHODS: NGAL TestTM (BioPorto Diagnostics A/S) is a particle-enhanced
      turbidimetric immunoassay. The within-and between-run imprecision were assessed
      on three urine samples. The linearity was assessed by serially diluting two urine
      samples with low and high NGAL concentration. The comparison study was performed
      with Abbott ARCHITECT NGAL, on 70 urine samples. RESULTS: The within-run
      imprecision was comprised between 1.0% and 2.3%, whereas the between-run
      imprecision was between 1.2% and 2.0%. The linearity was excellent in the range
      between 18 ng/mL and 790 ng/mL (r=1.000; p<0.001). A highly significant agreement
      was observed between NGAL TestTM on Beckman Coulter AU5822 and Abbott ARCHITECT
      NGAL (r=0.925; p<0.001), although the method exhibited a bias of +65%. Excellent
      sensitivity and specificity against the ARCHITECT values were found at 200 ng/mL.
      CONCLUSIONS: This analytical evaluation attests that the NGAL TestTM has several
      technical and analytical advantages, including no manual pretreatment, low volume
      of sample (i.e., 3 MUL), fast turnaround time (approx. 10 min), low imprecision,
      wide dynamic range, optimal linearity.

PMID- 22962214
TI  - Serum creatinine and the search for new biomarkers of acute kidney injury (AKI):
      the story continues.

PMID- 22962215
TI  - Interference of new oral anticoagulants with frequently used coagulation tests.

PMID- 22962216
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney
      injury: a review of the laboratory characteristics and clinical evidences.
AB  - Acute kidney injury (AKI) is a common and serious condition, currently diagnosed
      by functional biomarkers, such as serum creatinine measurements. Unfortunately,
      creatinine increase is a delayed and unreliable indicator of AKI. The lack of
      early biomarkers of structural kidney injury has hampered our ability to
      translate promising experimental therapies to human AKI. The recent discovery,
      translation and validation of neutrophil gelatinase-associated lipocalin (NGAL),
      possibly the most promising novel AKI biomarker, is reviewed here. NGAL may be
      measured by several methods both in plasma and urine for the early diagnosis of
      AKI and for the prediction of clinical outcomes, such as dialysis requirement and
      mortality, in several common clinical scenarios, including in the intensive care
      unit, cardiac surgery and renal damage due the exposition to toxic agent and
      drugs, and renal transplantation. Furthermore, the predictive properties of NGAL,
      may play a critical role in expediting the drug development process. A systematic
      review of literature data indicates that further studies are necessary to
      establish accurate reference population values according to age, gender and
      ethnicity, as well as reliable and specific decisional values concerning the more
      common clinical settings related to AKI. Furthermore, proper randomized clinical
      trials on renal and systemic outcomes comparing the use of NGAL vs. standard
      clinical practice are still lacking and accurate cost-benefit and/or cost-utility
      analyses for NGAL as biomarker of AKI are also needed. However, it is important
      to note that NGAL, in the absence of diagnostic increases in serum creatinine, is
      able to detect some patients affected by subclinical AKI who have an increased
      risk of adverse outcomes. These results also suggest that the concept and
      definition of AKI might need to be reassessed.

PMID- 22962217
TI  - Proposals for the mitigation of the environmental impact of clinical
      laboratories.
AB  - Laboratories should be aware of the carbon footprint resulting from their
      activities and take steps to mitigate it as part of their societal
      responsibilities. Once committed to a mitigation programme, they should announce
      an environmental policy, secure the support of senior management, initiate
      documentation, institute a staff training programme, schedule environmental
      audits and appoint an environmental manager. Laboratories may aspire to be
      accredited to one of the standards for environmental management, such as the ISO
      14000. As environmental and quality issues are linked, the improvement in the
      environmental management of an organisation will ultimately lead to improved
      quality system performance. Indeed, environmental management could conceivably
      come under overall quality management. Although there will be initial costs, good
      environmental practices can bring savings. Environmental improvement should be
      based on the 3R concept to reduce, reuse and recycle. Several policy initiatives
      may be introduced. These include a green purchasing policy for equipment,
      laboratory furniture and reagents as well as the management of packaging wastes.
      There are several ways to reduce energy, water usage and wastage. A reduction of
      test numbers and collection tubes should be attempted. Paper management involves
      all aspects of 3R. The recycling of solvents and general wastes should be
      practised where feasible. The construction new laboratories or renovations to
      existing ones are opportunities to make them more environmentally-friendly. The
      advocacy of policies to associates and the inclusion of environmentally-friendly
      conditions on contractors are integral parts of the programme.

PMID- 22962218
TI  - Variation of serum and urinary neutrophil gelatinase associated lipocalin (NGAL)
      after strenuous physical exercise.
AB  - BACKGROUND: Strenuous exercise may trigger acute complications, such as
      exertional rhabdomyolysis and gastrointestinal complaint. As less is known about
      the potential renal impairment after long distance running, we assessed
      creatinine and neutrophil gelatinase associated lipocalin (NGAL) in serum (sNGAL)
      and urine (uNGAL) before and after an ultramarathon. METHODS: The study
      population consisted of 16 trained male athletes who ran a 60 km ultramarathon.
      Blood and spot urine samples were collected 20 min before and immediately after
      the run. Creatinine was assessed by Jaffe assay on Beckman Coulter AU5800 and
      renal function was expressed as estimated glomerular filtration rate (eGFR) by
      MDRD formula. NGAL was measured by fully-automated immunoassay NGAL TestTM on AU
      5800. RESULTS: Serum and urinary creatinine increased significantly by 38% and
      78%, respectively. The eGFR contextually decreased by 31%. sNGAL, uNGAL and
      uNGAL/creatinine ratio increased by 1.6-fold, 7.7-fold and 2.9-fold. In six of 16
      athletes (38%), the acute post-exercise increase of serum creatinine met the
      criteria of acute kidney injury. No significant relationship was found between
      pre-exercise, post-exercise values and post-exercise variation of sNGAL, uNGAL
      and uNGAL/creatinine ratio. A significant correlation was found between pre- and
      post-exercise changes of serum creatinine and sNGAL, but not with either uNGAL or
      uNGAL/creatinine ratio. CONCLUSIONS: The acute variations of serum creatinine and
      uNGAL attest that renal impairment is likely to develop after long distance
      running. The uNGAL seems more independent from creatinine variation and extra
      renal sources, and thereby more reliable for monitoring the renal involvement in
      these types of kidney impairment.

PMID- 22962219
TI  - Analytic and clinical validation of a standardized cystatin C particle enhanced
      turbidimetric assay (PETIA) to estimate glomerular filtration rate.
AB  - BACKGROUND: Cystatin C is an alternative biomarker for assessing glomerular
      filtration rate (GFR), yet lack of standardization could hinder its widespread
      use. In this study we analytically and clinically validated a newer cystatin C
      particle-enhanced turbidimetric assay (PETIA) traceable to a certified reference
      material and compared it to the more commonly used particle-enhanced
      nephelometric assay (PENIA). METHODS: Samples from four patient cohorts at the
      Mayo Clinic were studied: 1) clinical convenience samples (n=50); 2) samples from
      patients undergoing iothalamate urinary clearance testing for clinical
      indications (n=101); 3) volunteers without kidney disease (n=292); 4) samples
      from 1999-2000 with previous cystatin C measurements. RESULTS: The cystatin C
      PETIA was analytically robust between 0.15 mg/L and 8.36 mg/L. PETIA cystatin C
      values were 27.5% higher than PENIA results. Furthermore, PENIA results were
      12.9% lower in 2010 than in 2000. PETIA cystatin C values and existing equations
      performed reasonably well to estimate GFR with an overall -7.4% bias for all
      patients analyzed. Age and gender specific reference intervals were established
      for the PETIA cystatin C. CONCLUSIONS: Cystatin C can be precisely measured by
      PETIA traceable to the international reference material, ERM-DA471/IFCC, using a
      routine chemistry autoanalyzer. There are important biases between this assay and
      the widely employed Siemens PENIA. This study highlights the importance of assay
      standardization if cystatin C is to be widely used to estimate GFR.

PMID- 22962220
TI  - Compensating for the influence of total serum protein in the Schwartz formula.
AB  - BACKGROUND: The Schwartz 2009 creatinine-based revised formula is the only
      pediatric GFR estimating formula, which is compatible with the recent global
      creatinine standardization. This formula is only applicable if enzymatic
      creatinine methods are used. We propose an equation, taking into account the
      relative bias caused by serum proteins to use Jaffe based creatinine data for GFR
      estimation. METHODS: In a cohort study of 100 pediatric patients, serum
      creatinine was measured using a kinetic rate-blanked Jaffe assay (modified
      kinetic alkaline picrate method), a kinetic rate-blanked Jaffe compensated assay
      for reactive proteins and an enzymatic assay (creatinine plus method). Serum
      total protein, albumin, urea, uric acid and total bilirubin were measured with
      the use of commercial agents. RESULTS: The difference in serum creatinine between
      the enzymatic method and the compensated Jaffe method was mainly dependent on the
      total protein concentration in serum (r(2)=0.61, p<0.001). After applying the
      proposed protein correction, corrected compensated Jaffe results and creatinine
      clearance values became interchangeable with enzymatic serum creatinine results
      (r(2)=0.99, p<0.001; Deming regression: slope: 0.9787, intercept: -0.351) and
      with the newly proposed Schwartz formula, respectively (r(2)=0.99, p<0.001;
      Deming regression: slope 1.004, intercept: 2.16). CONCLUSIONS: In this study, we
      demonstrated the usability of the alkaline picrate method in the Schwartz
      formula, taking into account the relative bias caused by serum proteins.

PMID- 22962221
TI  - Testing for lupus anticoagulants--fresh or frozen?
AB  - BACKGROUND: There are no previous studies reporting the effect of using frozen
      thawed plasma on lupus anticoagulant ratios in kits with the combined screen and
      confirm assay. METHODS: In the following study we chose patients with elevated
      dilute Russel's viper venom test (dRVVT) normalized ratios and compared the test
      results of fresh to frozen-thawed plasma. Platelet counts ranged from 2 to
      7*10(3)/MUL (10(9)/L) after a second centrifugation before freezing. RESULTS:
      There were 13 out of 14 dRVVT test normalized ratios that decreased after
      freezing (p<0.001), leading to the misclassification of six of 14 patients with
      high values that decreased into the reference interval. CONCLUSION: The major
      finding of this study is that testing frozen-thawed plasma with platelet counts
      <10,000/MUL (10(9)/L) results in a significant decrease in dRVVT ratios. Although
      there was a consistent decrease in SCT normalized ratios as well, it did not lead
      to misclassifications.

PMID- 22962222
TI  - Effect of coagulation factors on discrepancies in International Normalized Ratio
      results between instruments.
AB  - BACKGROUND: The reasons for discrepancies between International Normalized Ratio
      (INR) results determined by point-of-care-instruments and laboratory measurements
      are not fully understood. In this study we investigated whether different levels
      of coagulation factors in the plasma of patients can explain some of the
      systematic and/or random parts of the difference in INR between the instruments.
      METHODS: Blood samples were collected at four different patient visits from each
      of 34 outpatients on warfarin treatment. INR was determined on a laboratory
      instrument (STA Compact((r))) and on three point-of-care instruments (Simple
      Simon((r))PT, CoaguChek((r))XS and INRatioTM). In addition, the level of
      fibrinogen, coagulation factors II, V, VII and X was determined. INR instruments
      were compared in pairs. Simple linear regressions as well as multiple linear
      regressions and nested ANOVA analyses were used to examine the data. RESULTS: The
      coagulation factors, especially fibrinogen, factors II and VII, could explain
      between 16% and 45% of the total variance of the differences in INR between
      instruments dependent on instruments compared. After correction for factors no
      systematic difference was seen for four of the six comparisons and the between-
      and within-subject variation of the differences were reduced by up to 69% and
      52%, respectively. CONCLUSIONS: By correcting for the appropriate coagulation
      factors, especially the systematic differences, but also the between- and within
      subject variation of the differences between instruments, were reduced. This
      indicates that different levels of coagulation factors in the plasma of the
      patients play an important role in explaining discrepancies between INR
      instruments.

PMID- 22962223
TI  - Comparison of capillary electrophoregram among heterozygous Hb Hope, Hb
      Hope/alpha-thalassemia-1 SEA type deletion and Hb Hope/beta(0)-thalassemia.
AB  - BACKGROUND: Hemoglobin (Hb) A(2) is artifactually elevated in cases of
      heterozygous Hb Hope when measured by capillary electrophoresis (CE). However,
      there is no report of HbA(2) levels and capillary electrophoregrams for
      associations of heterozygote of Hb Hope with alpha-thalassemia nor beta
      thalassemia. METHODS: Levels of HbA(0), HbA(2) and Hb Hope in 16 heterozygous Hb
      Hope, 3 Hb Hope/alpha-thalassemia-1 SEA type deletion and 2 Hb Hope/beta(0)
      thalassemia were measured by CE. Electrophoregram and the levels of those were
      compared within these three groups. RESULTS: Artifactually elevated HbA(2) levels
      (>=4%) were found in both groups of heterozygous Hb Hope and Hb Hope/alpha
      thalassemia-1 SEA type deletion. Manual corrections were performed by adjusting
      baselines, and results showed that means of HbA(2) in both groups decreased from
      4.47% and 4.03% to 1.93% and 1.77%, respectively. The highest levels of HbA(2)
      and Hb Hope were observed in samples with Hb Hope/beta(0)-thalassemia. Moreover,
      HbA(0) was not observed in these cases. CONCLUSIONS: The elevation of HbA(2) in
      patients with heterozygous Hb Hope and with Hb Hope/alpha-thalassemia-1 SEA type
      deletion measured by CE leads to incorrect beta-thalassemia trait diagnosis.
      However, using CE electrophoregram together with levels of HbA(0), HbA(2) and Hb
      Hope would be a more accurate and precise method for diagnosis of Hb Hope/beta(0)
      thalassemia.

PMID- 22962224
TI  - Aberrant lamellar body counts noted on the Beckman Coulter Unicel DxH 800.
AB  - BACKGROUND: The lamellar body count (LBC) plays a crucial role in fetal lung
      maturity testing. Lamellar bodies are often counted in the platelet channel of
      routine hematology analyzers, resulting in a rapid and inexpensive assay for
      fetal lung maturity. Recently, significant imprecision was noted during LBC
      validation on the Beckman Coulter Unicel DxH 800. METHODS: The results of two
      Beckman Coulter Unicel DxH 800 instruments were compared to those of a Coulter LH
      750 and Coulter LH 500. Three pools of amniotic fluid, commercial quality control
      materials, and proficiency test specimens were analyzed on all four instruments.
      Fifty patient specimens were also analyzed using the Coulter LH 500 and the
      Unicel DxH 800. RESULTS: The mean values and precision obtained from commercial
      quality control materials and proficiency test samples were comparable on all
      four instruments. However, many erroneously low LBC results were produced from
      amniotic fluid pools using both DxH 800 instruments. The erroneous values were
      approximately 50% lower than respective target values, occurred randomly, and
      affected the low, medium, and high LBC results. Inter-assay precision of the
      three pools ranged from 24.7 to 39.0 CV% on the DxH 800 instruments. CONCLUSIONS:
      The source of LBC errors likely involves the exclusion of smaller lamellar bodies
      from the counts. The DxH 800 combines new data fusion technology and mathematical
      algorithms to produce increased accuracy and flagging efficiency. Laboratorians
      should be aware that the improved specificity of the DxH 800 may preclude its use
      for this laboratory-developed test.

PMID- 22962225
TI  - Plasma betaine concentrations correlate with plasma cortisol but not with C
      reactive protein in an elderly population.
AB  - BACKGROUND: Low plasma betaine concentrations are a feature of seriously ill
      patients. Increased dietary betaine intake has been associated with lowered
      systemic inflammation. We aimed to compare plasma cortisol (a stress marker) and
      C-reactive protein (an inflammation marker) as statistical predictors of plasma
      betaine concentrations. METHODS: Plasma carnitine, cortisol and C-reactive
      protein concentrations, other biochemical measures and urine betaine excretion,
      were compared with plasma betaine concentration by correlation and in multiple
      regression models, using morning blood and urine samples from 64 ambulant elderly
      subjects and from 55 patients admitted to hospital with hip fractures. RESULTS:
      In the ambulant elderly without acute trauma, plasma cortisol (with negative
      coefficients) and carnitine (with positive coefficients) statistically predicted
      plasma betaine concentrations. C-reactive protein was not a predictor. In the
      patients, the significant predictors were plasma carnitine (positive coefficient)
      and plasma homocysteine (negative coefficient) and C-reactive protein again was
      not a predictor. In regression models using combined patient and control data
      there were large ranges of both cortisol and especially C-reactive protein;
      cortisol and homocysteine (negative coefficients) and carnitine (positive
      coefficient) were significant predictors but C-reactive protein was not
      significant. CONCLUSIONS: Stress rather than inflammation may affect plasma
      betaine concentrations.

PMID- 22962226
TI  - Determinants of the essential one-carbon metabolism metabolites, homocysteine, S
      adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.
AB  - BACKGROUND: Disturbances in the levels of one-carbon (1C) metabolism metabolites
      have been associated with a wide variety of neuropsychiatric diseases.
      Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C
      metabolites, nor their interrelatedness and putative determinants, have been
      studied extensively in a healthy population. METHODS: Plasma and CSF samples from
      100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45
      female; age 50+/-17 years). In blood, we measured plasma Hcy, serum folate and
      serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S
      adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly
      selective analytical methods like liquid chromatography combined with either mass
      spectrometry or fluorescence detection were used. RESULTS: CSF Hcy was inversely
      correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of
      serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and
      higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age
      and positive correlations with serum folate. CSF SAM did not correlate with any
      of the 1C metabolites. CONCLUSIONS: Aging is characterized by a reduction in CSF
      5-methylTHF levels and increased CSF levels of the potentially neurotoxic
      transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in
      part by systemic folate status, is a powerful independent determinant of CSF
      levels of Hcy and SAH.

PMID- 22962227
TI  - Application of a modified precipitation method for the measurement of small dense
      LDL-cholesterol (sd-LDL-C) in a population in southern Brazil.
AB  - BACKGROUND: In the study reported herein, we used the precipitation method
      employing heparin-Mg(2+), with slight modifications to avoid lipemia
      interference, to measure small dense-low density lipoprotein-cholesterol (sd-LDL
      C) in Brazilian subjects with a high risk of developing cardiovascular diseases.
      METHODS: Lipemic samples were diluted with various solvents prior to
      precipitation with heparin-Mg(2+). Validation assays were performed with
      ultracentrifugation (n=100) and the reproducibility of sd-LDL-C measured in
      diluted serum (n=50). The applicability of this modification was evaluated by
      measuring sd-LDL-C in 434 southern Brazilian normolipidemic, dyslipidemic and
      type 2 diabetes mellitus (T2DM) individuals. RESULTS: Lipemic serum diluted with
      100 mmol/L phosphate buffer pH 8.5 was effective for the quantification of sd-LDL
      C, which was correlated with non-diluted serum (r=0.961; p<0.0001) and with
      ultracentrifugation (r=0.705; p<0.0001). Ultracentrifugation sd-LDL-C was 0.08
      mmol/L (CI 95%: -0.42-0.58 mmol/L) higher than the precipitation method (p>0.05).
      Subjects with dyslipidemias and T2DM had, respectively, 2.3 and 2.6-fold higher
      sd-LDL-C concentrations than normolipidemic individuals (p<0.05). The incidence
      of normolipidemic subjects with a high concentration of sd-LDL-C was only 2.2%.
      The sd-LDL-C was found to be enhanced by 8.3% every 10 years and young
      normolipidemic men had 24% higher sd-LDL-C than young women (p<0.05). Lipid
      lowering therapy reduced sd-LDL-C by 26% (p<0.001). CONCLUSIONS: In this paper we
      described a simple and inexpensive approach to improving the measurement of sd
      LDL-C in high-triglycerides serum. Furthermore, we showed that southern Brazil
      dyslipidemic and T2DM individuals have increased sd-LDL-C concentrations.

PMID- 22962228
TI  - BCR-ABL fusion protein detection in peripheral blood and bone marrow samples of
      adult precursor B-cell acute lymphoblastic leukemia patients using the flow
      cytometric immunobead assay.
AB  - BACKGROUND: The ability to detect the BCR-ABL fusion gene in precursor B-cell
      acute lymphoblastic leukemia (pB-ALL) is essential for making accurate treatment
      decisions. METHODS: We used a new flow cytometric immunobead assay for BCR-ABL
      fusion protein detection in peripheral blood and/or bone marrow samples from 38
      adult pB-ALL patients and the results were compared with polymerase chain
      reaction (PCR) detection of BCR-ABL transcript. RESULTS: The fusion protein was
      detected in peripheral blood and bone marrow samples from seven of the 38 (18%)
      patients, and results for both the p190 and p210 were confirmed by PCR. One case,
      which was positive by cytogenetics and fluorescence in situ hybridization (FISH),
      was negative by PCR but positive by flow cytometry. Another case, which was
      positive by PCR and negative by flow cytometry, was from a patient on steroid
      treatment. CONCLUSIONS: The cytometric immunobead assay for BCR-ABL fusion
      protein detection was found to be suitable for the investigation of pB-ALL
      patients. This assay is reliable, rapid and simple to use for peripheral blood
      and bone marrow samples.

PMID- 22962229
TI  - Neutrophil gelatinase-associated lipocalin: comparison of the use of EDTA and
      heparin plasma.

PMID- 22962230
TI  - Time- and temperature-dependent stability of troponin standard reference material
      2921 in serum and plasma.

PMID- 22962231
TI  - Effect of high RNA concentrations in real time reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) yields.

PMID- 22962232
TI  - Phosphate inhibits calcium oxalate crystal growth and crystallization through
      reducing free calcium ions: a morphological analysis and calcium consumption
      assay.

PMID- 22962233
TI  - Descriptions from accelerated baccalaureate nurses: determining curriculum and
      clinical strategies that work best to prepare novice nurses.
AB  - Newly graduated accelerated baccalaureate nurses have completed a rigorous,
      condensed curriculum; however, there is little research on their transition into
      the professional role. The purpose of this qualitative, descriptive research was
      to elicit novice nurses' descriptions of the transition into actual nursing, and
      to identify curriculum and clinical strategies that either facilitated or
      hindered their transition. As areas that enhanced their professional transition,
      participants reported a high intensity, fast-paced program and dynamic, mentoring
      clinical faculty who demonstrated skills to analyze patient situations. Factors
      that hindered their transition were insufficient clinical time and lack of a
      welcoming and supportive staff at clinical locations. Based on the findings from
      this study, the researcher recommends synchronizing accelerated nursing content
      across all baccalaureate courses and adding more clinical time that is directed
      by a supportive and enthusiastic faculty member who provides pertinent,
      individualized patient assignments.

PMID- 22962234
TI  - Adding dishes to the academic platter...

PMID- 22962235
TI  - Patent ductus arteriosus--looking for the right approach of management.

PMID- 22962236
TI  - Point of care estimation of blood glucose in neonates.

PMID- 22962237
TI  - Promoting appropriate management of diarrhea: a systematic review of literature
      for advocacy and action: UNICEF-PHFI series on newborn and child health, India.
AB  - BACKGROUND: Scaling up of evidence-based management and prevention of childhood
      diarrhea is a public health priority in India, and necessitates robust literature
      review, for advocacy and action. OBJECTIVE: To identify, synthesize and summarize
      current evidence to guide scaling up of management of diarrhea among under-five
      children in India, and identify existing knowledge gaps. METHODS: A set of
      questions pertaining to the management (prevention, treatment, and control) of
      childhood diarrhea was identified through a consultative process. A modified
      systematic review process developed a priori was used to identify, synthesize and
      summarize, research evidence and operational information, pertaining to the
      problem in India. Areas with limited or no evidence were identified as knowledge
      gaps. RESULTS: Childhood diarrhea is a significant public health problem in
      India; the point (two weeks) prevalence is 9 to 20%. Diarrhea accounts for 14% of
      the total deaths in under-five children in India. Infants aged 6 to 24 months are
      at the highest risk of diarrhea. There is a lack of robust nation-wide data on
      etiology; rotavirus and diarrheogenic E.coli are the most common organisms
      identified. The current National Guidelines are sufficient for case-management of
      childhood diarrhea. Exclusive breastfeeding, handwashing and point of use water
      treatment are effective strategies for prevention of all-cause diarrhea;
      rotavirus vaccines are efficacious to prevent rotavirus specific diarrhea. ORS
      and zinc are the mainstay of management during an episode of childhood diarrhea
      but have low coverage in India due to policy and programmatic barriers, whereas
      indiscriminate use of antibiotics and other drugs is common. Zinc therapy given
      during diarrhea can be upscaled through existing infrastructure is introducing
      the training component and information, education and communication activities.
      CONCLUSION: This systematic review summarizes current evidence on childhood
      diarrhea and provides evidence to inform child health programs in India.

PMID- 22962238
TI  - Does facility based newborn care improve neonatal outcomes? A review of evidence.
AB  - CONTEXT: Facility based newborn care is gaining importance as an intervention
      aiming at reduction of neonatal mortality. OBJECTIVE: To assess different factors
      that affect effectiveness of facility based newborn care on neonatal outcomes.
      EVIDENCE ACQUISITION: Electronic search using key search engines along with
      search of grey literature manually. Observational and interventional studies
      published between 1966-Aug 2010 in English having a change in neonatal mortality
      as an outcome measure were considered. RESULTS: A total of 40 articles were fully
      reviewed for generating synthesized evidence. All were observational studies. The
      exposure variables that affected neonatal outcomes were grouped into three
      categories- regionalization of perinatal care (17 articles), strengthening of
      lower level neonatal facilities (12), and other miscellaneous factors (11).
      Regionalization played a key role in advancing newborn care practices. It
      increased in-utero transfer of high risk newborns and improved survival outcomes
      especially for very low birth weight neonates at level III facilities. It led to
      reduction in neonatal mortality owing primarily to enhanced survival of low birth
      weight infants. Strengthening of lower level units contributed significantly in
      reducing neonatal mortality. High patient volume (>2,000 deliveries/year), inborn
      status, availability of referral system and inter-facility transfers, and
      adequate nursing care staff in neonatal units also demonstrated protective effect
      in averting neonatal deaths. CONCLUSIONS: Countries investing in facility based
      newborn care should give impetus to establishing regionalized systems of
      perinatal care. Strengthening of lower level units with high case loads, can
      yield optimal reduction in NMR.

PMID- 22962239
TI  - Effect of deworming vs Iron-Folic acid supplementation plus deworming on growth,
      hemoglobin level, and physical work capacity of schoolchildren.
AB  - The effect of deworming vs deworming and weekly Iron-Folic acid (IFA) on growth,
      hemoglobin level, and physical work capacity of children was studied. Children
      from three rural schools studying from 4th to 7th standard were selected. One set
      of school children were given deworming tablet (400 mg albendezole) once in six
      months while the second school children received deworming tablet along with
      weekly dose of Iron Folic acid Tablet (60 mg of elemental iron and 0.5 mg folic
      acid). Anthropometric measurements, hemoglobin, and physical work capacity was
      estimated. No significant change was noticed in the prevalence of malnutrition or
      physical work capacity of the children. As compared to only deworming, IFA +
      Deworming showed 17.3% increase in the hemoglobin levels (P<0.001). Thus weekly
      IFA along with deworming has shown beneficial effect on the hemoglobin levels of
      the children.

PMID- 22962240
TI  - Factors associated with delay in diagnosis of Kawasaki disease in India.
AB  - A retrospective analysis was carried out to identify factors associated with
      delay in diagnosis of Kawasaki disease in a tertiary care pediatric hospital
      setting in Chennai, India. Over a period of 2 years, a total of 37 cases were
      studied. The cases were divided into Early Diagnosis Group (EDG) and Delayed
      Diagnosis Group (DDG) with the cut-off for early diagnosis being ten days. A
      greater proportion of cases in the EDG presented primarily to our institution
      (P=0.004). In the DDG group greater number of cases had received medical
      attention from practicing pediatricians prior to referral. There was greater
      interval in onset of individual symptoms in the DDG group. There was no
      difference between the two groups with regard to age, gender, total blood counts,
      CRP, liver enzymes, urine analysis or serum albumin values. Platelet counts were
      higher in the DDG compared to the EDG (P=0.004).Coronary abnormalities were more
      common in the DDG (P=0.05). Our findings suggest that children presenting
      primarily to a tertiary care centre with symptoms of Kawasaki disease are more
      likely to be associated with early diagnosis and delay in onset of neck swelling
      or oral lesions may be associated with delayed diagnosis. There is a need for
      creating more awareness about Kawasaki disease among practicing pediatricians in
      India.

PMID- 22962241
TI  - Pseudohypoparathyroidism type 1b with hypothyroidism.
AB  - Pseudohypoparathyroidism due to deficient end organ response to parathyroid
      hormone (PTH) is characterized by hypocalcemia, hyperphosphatemia and increased
      serum PTH. We report a case of an 8-year-old girl with pseudohypoparathyroidism
      without features of Albright's hereditary osteodystrophy. The case is of interest
      as the child on serial follow-up over a period of 2 years developed
      hypothyroidism. This is a rare feature seen in pseudohypoparathyroidism type1b.

PMID- 22962242
TI  - Chronic myeloid leukemia in a child with IgA nephropathy.
AB  - We report an 11 year old boy with IgA nephropathy developing chronic myeloid
      leukemia on follow-up. This association suggests that a B cell defect might be
      involved in the pathogenesis of these two conditions.

PMID- 22962243
TI  - Facio-auriculo-vertebral sequence in association with congenital
      hypoparathyroidism.
AB  - Although, Facio-auriculo-vertebral sequence (FAVS) is a well recognized condition
      with cranio-facial, ocular and vertebral anomalies, extreme variability of
      expression is characteristic. Association of cardiac, CNS, lungs, kidneys and
      limb defects are described. We report a neonatal case with FAVS in association
      with congenital hypoparathyroidism.

PMID- 22962244
TI  - Rituximab for treatment of autoimmune hemolytic anemia.
AB  - We report the successful use of rituximab as single treatment modality in a five
      month-old boy with fulminant warm autoantibody autoimmune hemolytic anemia,
      resistant to standard treatment. On admission, laboratory tests showed a profound
      anemia with a hemoglobin of 2.6 g/dL. Indirect and direct antiglobulin tests were
      strongly positive, and nonspecific IgG autoantibodies were detected. Two days of
      intravenous corticosteroids (methylprednisolone 4mg/kg) and immunoglobulins
      (1g/kg) did not halt the hemolysis and the infant was severely transfusion
      dependent. Rituximab 375mg/sq m weekly was given for 4 weeks, the
      hepatosplenomegaly gradually regressed, the lymphocytes normalized and he is free
      from hemolysis two years after treatment.

PMID- 22962245
TI  - Retinopathy of prematurity experience from a secondary care center.
AB  - Retinopathy of prematurity (ROP) is an emerging cause of blindness. Few data are
      available from secondary care centres. Analyses of the incidence and risk factors
      for ROP from a secondary care center indicate that the incidence (19.7%) is
      higher than that noted in tertiary care centers.  This highlights the need to
      screen even big preterms (>1500 g or >32 wks) born at these centers for ROP.

PMID- 22962246
TI  - Growth and development profile of Indian children with Down syndrome.
AB  - In this retrospective study, we describe the profile of 88 children with Down
      syndrome.  The average BMI for children showed a progressive increase with age.
      Compared to the previously published development profile, there was a significant
      improvement in the language domain.

PMID- 22962247
TI  - HIV antibody tests for young infants: a lost opportunity to detect negative
      status.

PMID- 22962248
TI  - Spondylodiscitis with primary psoas abscess in a neonate.

PMID- 22962249
TI  - Deferiprone is superior to deferasirox and desferrioxamine in cardiac iron
      overload.

PMID- 22962250
TI  - Influenza epidemics in Iceland over 9 decades: changes in timing and synchrony
      with the United States and Europe.
AB  - Influenza epidemics exhibit a strongly seasonal pattern, with winter peaks that
      occur with similar timing across temperate areas of the Northern Hemisphere. This
      synchrony could be influenced by population movements, environmental factors,
      host immunity, and viral characteristics. The historical isolation of Iceland and
      subsequent increase in international contacts make it an ideal setting to study
      epidemic timing. The authors evaluated changes in the timing and regional
      synchrony of influenza epidemics using mortality and morbidity data from Iceland,
      North America, and Europe during the period from 1915 to 2007. Cross-correlations
      and wavelet analyses highlighted 2 major changes in influenza epidemic patterns
      in Iceland: first was a shift from nonseasonal epidemics prior to the 1930s to a
      regular winter-seasonal pattern, and second was a change in the early 1990s when
      a 1-month lag between Iceland and the United States and Europe was no longer
      detectable with monthly data. There was a moderate association between increased
      synchrony and the number of foreign visitors to Iceland, providing a plausible
      explanation for the second shift in epidemic timing. This suggests that
      transportation might have a minor effect on epidemic timing, but efforts to
      restrict air travel during influenza epidemics would likely have a limited
      impact, even for island populations.

PMID- 22962251
TI  - Non-invasive characterization of motor unit behaviour in pathological tremor.
AB  - This paper presents the fully automatic identification of motor unit spike trains
      from high-density surface electromyograms (EMG) in pathological tremor. First, a
      mathematical derivation is provided to theoretically prove the possibility of
      decomposing noise-free high-density surface EMG signals into motor unit spike
      trains with high correlation, which are typical of tremor contractions. Further,
      the proposed decomposition method is tested on simulated signals with different
      levels of noise and on experimental signals from 14 tremor-affected patients. In
      the case of simulated tremor with central frequency ranging from 5 Hz to 11 Hz
      and signal-to-noise ratio of 20 dB, the method identified ~8 motor units per
      contraction with sensitivity in spike timing identification >= 95% and false
      alarm and miss rates <= 5%. In experimental signals, the number of identified
      motor units varied substantially (range 0-21) across patients and contraction
      types, as expected. The behaviour of the identified motor units was consistent
      with previous data obtained by intramuscular EMG decomposition. These results
      demonstrate for the first time the possibility of a fully non-invasive
      investigation of motor unit behaviour in tremor-affected patients. The method
      provides a new means for physiological investigations of pathological tremor.

PMID- 22962252
TI  - Opposites attract: nanomagnetism in theory and practice.

PMID- 22962253
TI  - Estrogens and PTP1B function in a novel pathway to regulate aromatase enzymatic
      activity in breast cancer cells.
AB  - Local estrogen production by aromatase is an important mechanism of autocrine
      stimulation in hormone-dependent breast cancer. We have previously shown that 17
      beta estradiol (E(2)) rapidly enhances aromatase enzymatic activity through an
      increase of tyrosine protein phosphorylation controlled by the activity of the c
      Src kinase in breast cancer cells. Here, we investigated the protein tyrosine
      phosphatase PTP1B (protein tyrosine phosphatase 1B) as a potential regulator of
      aromatase activity. We demonstrated a specific association between PTP1B and
      aromatase at protein-protein level and a reduction of aromatase activity in basal
      and E(2)-treated MCF-7 and ZR75 breast cancer cells when PTP1B was overexpressed.
      Indeed, a specific tyrosine phosphatase inhibitor increased basal and E(2)
      induced enzymatic activity as well as tyrosine phosphorylation status of the
      purified aromatase protein. Moreover, E(2) through phosphatidylinositol 3
      kinase/Akt activation caused a significant decrease of PTP1B catalytic activity
      along with an increase in its serine phosphorylation. Concomitantly, the
      phosphatidylinositol 3 kinase inhibitor LY294002 or a dominant negative of Akt
      was able to reduce the E(2) stimulatory effects on activity and tyrosine
      phosphorylation levels of aromatase. Taken together, our results suggest that
      E(2) can impair PTP1B ability to dephosphorylate aromatase, and thus it increases
      its enzymatic activity, creating a positive feedback mechanism for estradiol
      signaling in breast cancer.

PMID- 22962254
TI  - Fetal glucocorticoid synthesis is required for development of fetal adrenal
      medulla and hypothalamus feedback suppression.
AB  - During pregnancy, fetal glucocorticoid is derived from both maternal supply and
      fetal secretion. We have created mice with a disruption of the Cyp11a1 gene
      resulting in loss of fetal steroid secretion but preserving the maternal supply.
      Cyp11a1null embryos have appreciable although lower amounts of circulating
      corticosterone, the major mouse glucocorticoid, suggesting that transplacental
      corticosterone is a major source of corticosterone in fetal circulation. These
      embryos thus provide a means to examine the effect of fetal glucocorticoids. The
      adrenal in Cyp11a1 null embryos was disorganized with abnormal mitochondria and
      oil accumulation. The adrenal medullary cells did not express phenylethanolamine
      N-methyltransferase and synthesized no epinephrine. Cyp11a1 null embryos had
      decreased diencephalon Hsd11b1, increased diencephalon Crh, and increased
      pituitary Pomc expression, leading to higher adrenocorticotropin level in the
      plasma. These data indicate blunted feedback suppression despite reasonable
      amounts of circulating corticosterone. Thus, the corticosterone synthesized in
      situ by the fetus is required for negative feedback suppression of the
      hypothalamus-pituitary-adrenal axis and for catecholamine synthesis in adrenal
      medulla.

PMID- 22962255
TI  - Molecular basis for glucocorticoid induction of the Kruppel-like factor 9 gene in
      hippocampal neurons.
AB  - Stress has complex effects on hippocampal structure and function, which
      consequently affects learning and memory. These effects are mediated in part by
      circulating glucocorticoids (GC) acting via the intracellular GC receptor (GR)
      and mineralocorticoid receptor (MR). Here, we investigated GC regulation of
      Kruppel-like factor 9 (KLF9), a transcription factor implicated in neuronal
      development and plasticity. Injection of corticosterone (CORT) in postnatal d 6
      and 30 mice increased Klf9 mRNA and heteronuclear RNA by 1 h in the hippocampal
      region. Treatment of the mouse hippocampal cell line HT-22 with CORT caused a
      time- and dose-dependent increase in Klf9 mRNA. The CORT induction of Klf9 was
      resistant to protein synthesis inhibition, suggesting that Klf9 is a direct CORT
      response gene. In support of this hypothesis, we identified two GR/MR response
      elements (GRE/MRE) located -6.1 and -5.3 kb relative to the transcription start
      site, and we verified their functionality by enhancer-reporter, gel shift, and
      chromatin immunoprecipitation assays. The -5.3-kb GRE/MRE is largely conserved
      across tetrapods, but conserved orthologs of the -6.1-kb GRE/MRE were only
      detected in therian mammals. GC treatment caused recruitment of the GR, histone
      hyperacetylation, and nucleosome removal at Klf9 upstream regions. Our findings
      support a predominant role for GR, with a minor contribution of MR, in the direct
      regulation of Klf9 acting via two GRE/MRE located in the 5'-flanking region of
      the gene. KLF9 may play a key role in GC actions on hippocampal development and
      plasticity.

PMID- 22962257
TI  - Vitamin D receptor activation induces peptide YY transcription in pancreatic
      islets.
AB  - Peptide YY (PYY) is a peptide hormone secreted from L cells in the intestine
      after food intake and regulates appetite and intestinal function. PYY is also
      expressed in the pancreas, but the mechanisms of regulation of pancreatic PYY
      expression have not been elucidated. The vitamin D receptor (VDR) is a nuclear
      receptor for the active form of vitamin D(3) and regulates numerous physiological
      processes. Because VDR is expressed in the pancreas, we investigated the role of
      pancreatic VDR activation and found that Pyy is a VDR target gene in the mouse
      pancreas. Treatment of mice with 1alpha-hydroxyvitamin D(3) increased plasma PYY
      levels. VDR activation increased mRNA and protein expression of PYY in the
      pancreatic islets of mice and pancreatic endocrine cell lines but did not change
      intestinal PYY expression. 1alpha-Hydroxyvitamin D(3)-dependent induction of
      pancreatic and plasma PYY was abolished in VDR-null mice. We identified a
      functional vitamin D-responsive element in the mouse Pyy promoter using chromatin
      immunoprecipitation assay, EMSA, and luciferase promoter assay. Thus, Pyy is a
      tissue-specific VDR target gene. The pancreatic VDR-PYY pathway may mediate a
      regulatory function of vitamin D in the neuroendocrine system.

PMID- 22962256
TI  - 17beta-estradiol and progesterone regulate expression of beta-amyloid clearance
      factors in primary neuron cultures and female rat brain.
AB  - The accumulation of beta-amyloid protein (Abeta) is a key risk factor in the
      development of Alzheimer's disease. The ovarian sex steroid hormones 17beta
      estradiol (E(2)) and progesterone (P(4)) have been shown to regulate Abeta
      accumulation, although the underlying mechanism(s) remain to be fully elucidated.
      In this study, we investigate the effects of E(2) and P(4) treatment on the
      expression levels of Abeta clearance factors including insulin-degrading enzyme,
      neprilysin, endothelin-converting enzyme 1 and 2, angiotensin-converting enzyme,
      and transthyretin, both in primary neuron cultures and female rat brains. Our
      results show that E(2) and P(4) affect the expression levels of several Abeta
      clearance factors in dose- and time-dependent manners. Most notably, expression
      of insulin-degrading enzyme is significantly increased by both hormones in
      cultured neurons and in vivo and is inversely associated with the soluble Abeta
      levels in vivo. These findings further define sex steroid hormone actions
      involved in regulation of Abeta, a relationship potentially important to
      therapeutic approaches aimed at reducing risk of Alzheimer's disease.

PMID- 22962258
TI  - Prevention of diabetes in db/db mice by dietary soy is independent of isoflavone
      levels.
AB  - Recent evidence points towards the beneficial use of soy proteins and isoflavones
      to improve glucose control and slow the progression of type 2 diabetes. Here, we
      used diabetic db/db mice fed a high soy-containing diet (SD) or a casein soy-free
      diet to investigate the metabolic effects of soy and isoflavones consumption on
      glucose homeostasis, hepatic glucose production, and pancreatic islet function.
      Male db/db mice fed with a SD exhibited a robust reduction in hyperglycemia
      (50%), correlating with a reduction in hepatic glucose production and preserved
      pancreatic beta-cell function. The rapid decrease in fasting glucose levels
      resulted from an inhibition of gluconeogenesis and an increase in glycolysis in
      the liver of db/db mice. Soy consumption also prevented the loss of pancreatic
      beta-cell mass and thus improved glucose-stimulated insulin secretion (3-fold),
      which partly accounted for the overall improvements in glucose homeostasis.
      Comparison of SD effects on hyperglycemia with differing levels of isoflavones or
      with purified isoflavones indicate that the beneficial physiological effects of
      soy are not related to differences in their isoflavone content. Overall, these
      findings suggest that consumption of soy is beneficial for improving glucose
      homeostasis and delaying the progression of diabetes in the db/db mice but act
      independently of isoflavone concentration.

PMID- 22962259
TI  - Ghrelin receptor expression and colocalization with anterior pituitary hormones
      using a GHSR-GFP mouse line.
AB  - Ghrelin is the endogenous ligand for the GH secretagogue receptor (GHSR) and
      robustly stimulates GH release from the anterior pituitary gland. Ghrelin also
      regulates the secretion of anterior pituitary hormones including TSH, LH,
      prolactin (PRL), and ACTH. However, the relative contribution of a direct action
      at the GHSR in the anterior pituitary gland vs. an indirect action at the GHSR in
      the hypothalamus remains undefined. We used a novel GHSR-enhanced green
      fluorescent protein (eGFP) reporter mouse to quantify GHSR coexpression with GH,
      TSH, LH, PRL, and ACTH anterior pituitary cells in males vs. females and in chow
      fed or calorie-restricted (CR) mice. GHSR-eGFP-expressing cells were only
      observed in anterior pituitary. The number of GHSR-eGFP-expressing cells was
      higher in male compared with females, and CR did not affect the GHSR-eGFP cell
      number. Double staining revealed 77% of somatotrophs expressed GHSR-eGFP in both
      males and females. Nineteen percent and 12.6% of corticotrophs, 21% and 9% of
      lactotrophs, 18% and 19% of gonadotrophs, and 3% and 9% of males and females,
      respectively, expressed GHSR-eGFP. CR increased the number of TSH cells, but
      suppressed the number of lactotrophs and gonadotrophs, expressing GHSR-eGFP
      compared with controls. These studies support a robust stimulatory action of
      ghrelin via the GHSR on GH secretion and identify a previously unknown sexual
      dimorphism in the GHSR expression in the anterior pituitary. CR affects GHSR-eGFP
      expression on lactotrophs, gonadotrophs, and thyrotrophs, which may mediate
      reproductive function and energy metabolism during periods of negative energy
      balance. The low to moderate expression of GHSR-eGFP suggests that ghrelin plays
      a minor direct role on remaining anterior pituitary cells.

PMID- 22962260
TI  - Graphene nanocomposite for biomedical applications: fabrication, antimicrobial
      and cytotoxic investigations.
AB  - Materials possessing excellent bacterial toxicity, while presenting low
      cytotoxicity to human cells, are strong candidates for biomaterials applications.
      In this study, we present the fabrication of a nanocomposite containing poly(N
      vinylcarbazole) (PVK) and graphene (G) in solutions and thin films. Highly
      dispersed PVK-G (97-3 w/w%) solutions in various organic and aqueous solvents
      were prepared by solution mixing and sonication methods. The thermal properties
      and morphology of the new composite were analyzed using thermal gravimetry
      analysis (TGA) and atomic force microscopy (AFM), respectively. PVK-G films were
      immobilized onto indium tin oxide (ITO) substrates via electrodeposition. AFM was
      used to characterize the resulting topography of the nanocomposite thin films,
      while cyclic voltammetry and UV-vis were used to monitor their successful
      electrodeposition. The antimicrobial properties of the electrodeposited PVK-G
      films and solution-based PVK-G were investigated against Escherichia coli (E.
      coli) and Bacillus subtilis (B. subtilis). Microbial growth after exposure to the
      nanocomposite, metabolic assay and live-dead assay of the bacterial solutions
      exposed to PVK-G presented fewer viable and active bacteria than those exposed to
      pure PVK or pure graphene solutions. The PVK-G film inhibited about 80% of
      biofilm surface coverage whereas the PVK- and G-modified surfaces allowed biofilm
      formation over almost the whole coated surface (i.e. > 80%). The biocompatibility
      of the prepared PVK-G solutions on NIH 3T3 cells was evaluated using the MTS cell
      proliferation assay. A 24 h exposure of the PVK-G nanocomposite to the NIH 3T3
      cells presented ~80% cell survival.

PMID- 22962261
TI  - Fabrication of magnetic artificial atoms.
AB  - We have fabricated gated vertical quantum dots made from a II-VI semiconductor
      heterostructure containing a paramagnetic quantum well. The absence of a known
      Schottky gate metal compatible with ZnSe based material precludes the traditional
      method of using a self-aligning shadow evaporated gate. Instead, we make use of a
      multi-step electron beam lithography process to surround a pillar with an
      insulating dielectric and gate. This process allows for the processing of dots
      with diameters down to 250 nm. Preliminary transport data confirming the magnetic
      nature of the resulting artificial atom are presented.

PMID- 22962262
TI  - Ion transport through a graphene nanopore.
AB  - Molecular dynamics simulation is utilized to investigate the ionic transport of
      NaCl in solution through a graphene nanopore under an applied electric field.
      Results show the formation of concentration polarization layers in the vicinity
      of the graphene sheet. The nonuniformity of the ion distribution gives rise to an
      electric pressure which drives vortical motions in the fluid if the electric
      field is sufficiently strong to overcome the influence of viscosity and thermal
      fluctuations. The relative importance of hydrodynamic transport and thermal
      fluctuations in determining the pore conductivity is investigated. A second
      important effect that is observed is the mass transport of water through the
      nanopore, with an average velocity proportional to the applied voltage and
      independent of the pore diameter. The flux arises as a consequence of the
      asymmetry in the ion distribution which can be attributed to differing mobilities
      of the sodium and chlorine ions and to the polarity of water molecules. The
      accumulation of liquid molecules in the vicinity of the nanopore due to re
      orientation of the water dipoles by the local electric field is seen to result in
      a local increase in the liquid density. Results confirm that the electric
      conductance is proportional to the nanopore diameter for the parameter regimes
      that we simulated. The occurrence of fluid vortices is found to result in an
      increase in the effective electrical conductance.

PMID- 22962263
TI  - Hypoxia-inducible miR-210 regulates the susceptibility of tumor cells to lysis by
      cytotoxic T cells.
AB  - Hypoxia in the tumor microenvironment plays a central role in the evolution of
      immune escape mechanisms by tumor cells. In this study, we report the definition
      of miR-210 as a miRNA regulated by hypoxia in lung cancer and melanoma,
      documenting its involvement in blunting the susceptibility of tumor cells to
      lysis by antigen-specific cytotoxic T lymphocytes (CTL). miR-210 was induced in
      hypoxic zones of human tumor tissues. Its attenuation in hypoxic cells
      significantly restored susceptibility to autologous CTL-mediated lysis,
      independent of tumor cell recognition and CTL reactivity. A comprehensive
      approach using transcriptome analysis, argonaute protein immunoprecipitation, and
      luciferase reporter assay revealed that the genes PTPN1, HOXA1, and TP53I11 were
      miR-210 target genes regulated in hypoxic cells. In support of their primary
      importance in mediating the immunosuppressive effects of miR-210, coordinate
      silencing of PTPN1, HOXA1, and TP53I11 dramatically decreased tumor cell
      susceptibility to CTL-mediated lysis. Our findings show how miR-210 induction
      links hypoxia to immune escape from CTL-mediated lysis, by providing a
      mechanistic understanding of how this miRNA mediates immunosuppression in oxygen
      deprived regions of tumors where cancer stem-like cells and metastatic cellular
      behaviors are known to evolve.

PMID- 22962264
TI  - Targeting BRCA1 localization to augment breast tumor sensitivity to poly(ADP
      Ribose) polymerase inhibition.
AB  - PARP inhibitors have gained recent attention due to their highly selective
      killing of BRCA1/2-mutated and DNA double-strand break (DSB) repair-deficient
      tumors. Unfortunately, the majority of sporadic breast cancers carry wild-type
      BRCA1/2 and are proficient in DSB repair. We and others have shown that BRCA1 is
      a nuclear/cytoplasm shuttling protein that is transiently exported from the
      nucleus to the cytosol upon various stimuli. Thus, we hypothesized that depletion
      of nuclear BRCA1 would compromise DSB repair and subsequently render sporadic
      tumors susceptible to PARP inhibition. Indeed, in human sporadic breast cancer
      cells with functional BRCA1 and proficient DSB repair, a transient nuclear
      depletion of BRCA1 and subsequent homologous recombination repair deficit was
      induced with either truncated BRCA1 or irradiation. This rendered these human
      sporadic breast cancer cells susceptible to PARP inhibition. These observations
      were confirmed genetically using mislocated BRCA1 mutants as well as in vivo in
      mice bearing breast tumor xenografts. These data support the potential strategy
      of targeting BRCA1 location to convert BRCA1-proficient sporadic tumors to be
      susceptible to the synthetic lethal combination with PARP inhibitors.

PMID- 22962266
TI  - Cancer cells cue the p53 response of cancer-associated fibroblasts to cisplatin.
AB  - Current understanding of the p53 response is based mainly upon in vitro studies
      of homogeneous cell populations. However, there is little information on whether
      the same principles operate within heterogeneous tumor tissues that are comprised
      of cancer cells and other cell types, including cancer-associated fibroblasts
      (CAF). Using ex-vivo tissue cultures, we investigated p53 status and responses to
      cisplatin in tumor cells and CAFs from tissue specimens isolated from 32 lung
      cancer patients. By comparing cultivated tissue slices with the corresponding
      tumor tissues fixed immediately after surgery, we found that morphology,
      proliferation, and p53 staining pattern were preserved during cultivation.
      Unexpectedly, when CAFs were analyzed, p53 accumulation and induction of p21 was
      observed only in tumors with constitutively low p53 protein and accumulation upon
      cisplatin treatment. In contrast, in tumors with no p53 accumulation in cancer
      cells there was also no p53 accumulation or p21 induction in adjacent CAFs.
      Furthermore, induction of cisplatin-induced apoptosis in CAFs was selectively
      observed in tumors characterized by a parallel induction of cancer cell death.
      Our findings reveal an interdependence of the p53 response in cancer cells and
      adjacent CAFs within tumor tissues, arguing that cancer cells control the
      response of their microenvironment to DNA damage.

PMID- 22962265
TI  - Cross-species functional analysis of cancer-associated fibroblasts identifies a
      critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo.
AB  - Cancer-associated fibroblasts (CAF) have been reported to support tumor
      progression by a variety of mechanisms. However, their role in the progression of
      non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the
      extent to which specific proteins secreted by CAFs contribute directly to tumor
      growth is unclear. To study the role of CAFs in NSCLCs, a cross-species
      functional characterization of mouse and human lung CAFs was conducted. CAFs
      supported the growth of lung cancer cells in vivo by secretion of soluble factors
      that directly stimulate the growth of tumor cells. Gene expression analysis
      comparing normal mouse lung fibroblasts and mouse lung CAFs identified multiple
      genes that correlate with the CAF phenotype. A gene signature of secreted genes
      upregulated in CAFs was an independent marker of poor survival in patients with
      NSCLC. This secreted gene signature was upregulated in normal lung fibroblasts
      after long-term exposure to tumor cells, showing that lung fibroblasts are
      "educated" by tumor cells to acquire a CAF-like phenotype. Functional studies
      identified important roles for CLCF1-CNTFR and interleukin (IL)-6-IL-6R signaling
      in promoting growth of NSCLCs. This study identifies novel soluble factors
      contributing to the CAF protumorigenic phenotype in NSCLCs and suggests new
      avenues for the development of therapeutic strategies.

PMID- 22962267
TI  - Microdistribution and long-term retention of 239Pu (NO3)4 in the respiratory
      tracts of an acutely exposed plutonium worker and experimental beagle dogs.
AB  - The long-term retention of inhaled soluble forms of plutonium raises concerns as
      to the potential health effects in persons working in nuclear energy or the
      nuclear weapons program. The distributions of long-term retained inhaled
      plutonium-nitrate [(239)Pu (NO(3))(4)] deposited in the lungs of an accidentally
      exposed nuclear worker (Human Case 0269) and in the lungs of experimentally
      exposed beagle dogs with varying initial lung depositions were determined via
      autoradiographs of selected histologic lung, lymph node, trachea, and nasal
      turbinate tissue sections. These studies showed that both the human and dogs had
      a nonuniform distribution of plutonium throughout the lung tissue. Fibrotic scar
      tissue effectively encapsulated a portion of the plutonium and prevented its
      clearance from the body or translocation to other tissues and diminished dose to
      organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case
      0269 was observed primarily along the subpleural regions while no alpha activity
      was seen in the tracheobronchial lymph nodes of this individual. However,
      relatively high activity levels in the tracheobronchial lymph nodes of the
      beagles indicated the lymphatic system was effective in clearing deposited
      plutonium from the lung tissues. In both the human case and beagle dogs, the
      appearance of retained plutonium within the respiratory tract was inconsistent
      with current biokinetic models of clearance for soluble forms of plutonium. Bound
      plutonium can have a marked effect on the dose to the lungs and subsequent
      radiation exposure has the potential to increase cancer risk.

PMID- 22962268
TI  - CDK1 regulates mediator of DNA damage checkpoint 1 during mitotic DNA damage.
AB  - Cells engage sophisticated programs of DNA damage response (DDR) and repair to
      guard against genetic mutations. Although there is significant knowledge
      concerning DDR in interphase cells, much less is known about these processes in
      mitosis. Direct interaction between MDC1, a master DDR organizer, and a marker of
      DNA damage, histone gammaH2AX, is required to trigger robust repair. Here we show
      that the DNA damage-induced interaction between MDC1 and gammaH2AX is attenuated
      in mitosis. Furthermore, inhibition in the activity of the core mitotic regulator
      CDK1, either by pharmacologic inhibition or siRNA attenuation, enhances MDC1
      gammaH2AX colocalization in mitosis. Our findings offer key new insights into how
      DDR is controlled during mitosis.

PMID- 22962269
TI  - Iodide transporter NIS regulates cancer cell motility and invasiveness by
      interacting with the Rho guanine nucleotide exchange factor LARG.
AB  - A number of solute carrier (SLC) proteins are subject to changes in expression
      and activity during carcinogenesis. Whether these changes play a role in
      carcinogenesis is unclear, except for some nutrients and ion carriers whose
      deregulation ensures the necessary reprogramming of energy metabolism in cancer
      cells. In this study, we investigated the functional role in tumor progression of
      the sodium/iodide symporter (NIS; aka SLC5A5), which is upregulated and
      mislocalized in many human carcinomas. Notably, we found that NIS enhanced cell
      migration and invasion without ion transport being involved. These functions were
      mediated by NIS binding to leukemia-associated RhoA guanine exchange factor, a
      Rho guanine exchange factor that activates the small GTPase RhoA. Sequestering
      NIS in intracellular organelles or impairing its targeting to the cell surface
      (as observed in many cancers) led to a further increase in cell motility and
      invasiveness. In sum, our results established NIS as a carrier protein that
      interacts with a major cell signaling hub to facilitate tumor cell locomotion and
      invasion.

PMID- 22962271
TI  - Genetic screening for synthetic lethal partners of polynucleotide
      kinase/phosphatase: potential for targeting SHP-1-depleted cancers.
AB  - A genetic screen using a library of 6,961 siRNAs led to the identification of SHP
      1 (PTPN6), a tumor suppressor frequently mutated in malignant lymphomas,
      leukemias, and prostate cancer, as a potential synthetic lethal partner of the
      DNA repair protein polynucleotide kinase/phosphatase (PNKP). After confirming the
      partnership with SHP-1, we observed that codepletion of PNKP and SHP-1 induced
      apoptosis. A T-cell lymphoma cell line that is SHP-1 deficient (Karpas 299) was
      shown to be sensitive to a chemical inhibitor of PNKP, but resistance was
      restored by expression of wild-type SHP-1 in these cells. We determined that
      while SHP-1 depletion does not significantly impact DNA strand-break repair, it
      does amplify the level of reactive oxygen species (ROS) and elevate endogenous
      DNA damage. The ROS scavenger WR1065 afforded protection to SHP-1-depleted cells
      treated with the PNKP inhibitor. We propose that codisruption of SHP-1 and PNKP
      leads to an increase in DNA damage that escapes repair, resulting in the
      accumulation of cytotoxic double-strand breaks and induction of apoptosis. This
      supports an alternative paradigm for synthetic lethal partnerships that could be
      exploited therapeutically.

PMID- 22962270
TI  - T-cell trafficking facilitated by high endothelial venules is required for tumor
      control after regulatory T-cell depletion.
AB  - The evolution of immune blockades in tumors limits successful antitumor immunity,
      but the mechanisms underlying this process are not fully understood. Depletion of
      regulatory T cells (Treg), a T-cell subset that dampens excessive inflammatory
      and autoreactive responses, can allow activation of tumor-specific T cells.
      However, cancer immunotherapy studies have shown that a persistent failure of
      activated lymphocytes to infiltrate tumors remains a fundamental problem. In
      evaluating this issue, we found that despite an increase in T-cell activation and
      proliferation following Treg depletion, there was no significant association with
      tumor growth rate. In contrast, there was a highly significant association
      between low tumor growth rate and the extent of T-cell infiltration. Further
      analyses revealed a total concordance between low tumor growth rate, high T-cell
      infiltration, and the presence of high endothelial venules (HEV). HEV are blood
      vessels normally found in secondary lymphoid tissue where they are specialized
      for lymphocyte recruitment. Thus, our findings suggest that Treg depletion may
      promote HEV neogenesis, facilitating increased lymphocyte infiltration and
      destruction of the tumor tissue. These findings are important as they point to a
      hitherto unidentified role of Tregs, the manipulation of which may refine
      strategies for more effective cancer immunotherapy.

PMID- 22962272
TI  - DNA methylation biomarkers offer improved diagnostic efficiency in lung cancer.
AB  - The exceptional high mortality of lung cancer can be instigated to a high degree
      by late diagnosis. Despite the plethora of studies on potential molecular
      biomarkers for lung cancer diagnosis, very few have reached clinical
      implementation. In this study, we developed a panel of DNA methylation biomarkers
      and validated their diagnostic efficiency in bronchial washings from a large
      retrospective cohort. Candidate targets from previous high-throughput approaches
      were examined by pyrosequencing in an independent set of 48 lung tumor/normal
      paired. Ten promoters were selected and quantitative methylation-specific PCR
      (qMSP) assays were developed and used to screen 655 bronchial washings from the
      Liverpool Lung Project (LLP) subjects divided into training (194 cases and 214
      controls) and validation (139 cases and 109 controls) sets. Three statistical
      models were used to select the optimal panel of markers and to evaluate the
      performance of the discriminatory algorithms. The final logit regression model
      incorporated hypermethylation at p16, TERT, WT1, and RASSF1. The performance of
      this 4-gene methylation signature in the validation set showed 82% sensitivity
      and 91% specificity. In comparison, cytology alone in this set provided 43%
      sensitivity at 100% specificity. The diagnostic efficiency of the panel did not
      show any biases with age, gender, smoking, and the presence of a nonlung
      neoplasm. However, sensitivity was predictably higher in central (squamous and
      small cell) than peripheral (adenocarcinomas) tumors, as well as in stage 2 or
      greater tumors. These findings clearly show the impact of DNA methylation-based
      assays in the diagnosis of cytologically occult lung neoplasms. A prospective
      trial is currently imminent in the LLP study to provide data on the enhancement
      of diagnostic accuracy in a clinical setting, including by additional markers.

PMID- 22962275
TI  - Effective combination therapy for malignant glioma with TRAIL-secreting
      mesenchymal stem cells and lipoxygenase inhibitor MK886.
AB  - The apoptotic ligand TRAIL is believed to have promise as a cancer gene therapy,
      yet many types of cancer, including gliomas, have exhibited resistance to TRAIL
      induced apoptosis. Here, we show that therapeutic combination of the lipoxygenase
      inhibitor MK886 and TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL)
      provide targeted and prolonged delivery of TRAIL both in vitro and in orthotopic
      mouse models of glioma. Treatment of either TRAIL-sensitive or TRAIL-resistant
      human glioma cells with MK886 and MSC-TRAIL resulted in significantly enhanced
      apoptosis compared with each agent alone. MK886 effectively increased the
      sensitivity to TRAIL-induced apoptosis via upregulation of the death receptor 5
      and downregulation of the antiapoptotic protein survivin in human glioma cell
      lines and in primary glioma cells. This regulation was accompanied by a
      substantial increase in caspase activation after combined treatment. Furthermore,
      in vivo survival experiments and imaging analysis in orthotopic xenografted mice
      showed that MSC-based TRAIL gene delivery combined with MK886 into the tumors had
      greater therapeutic efficacy than single-agent treatment. Together, our findings
      indicate that MK886 combined with MSC-based TRAIL gene delivery may represent a
      novel strategy for improving the treatment of malignant gliomas.

PMID- 22962276
TI  - Role of the human high-affinity copper transporter in copper homeostasis
      regulation and cisplatin sensitivity in cancer chemotherapy.
AB  - The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in
      regulating copper homeostasis because copper is an essential micronutrient and
      copper deficiency is detrimental to many important cellular functions, but excess
      copper is toxic. Recent research has revealed that human copper homeostasis is
      tightly controlled by interregulatory circuitry involving copper, Sp1, and human
      (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in
      modulating hCtr1 expression, which in turn controls cellular copper and Sp1
      levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1
      expression by copper stresses has also been described in the literature. Because
      hCtr1 can also transport platinum drugs, this finding underscores the important
      role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent
      with this notion is the finding that elevated hCtr1 expression was associated
      with favorable treatment outcomes in cisplatin-based cancer chemotherapy.
      Moreover, cultured cell studies showed that elevated hCtr1 expression can be
      induced by depleting cellular copper levels, resulting in enhanced cisplatin
      uptake and its cell-killing activity. A phase I clinical trial using a
      combination of trientine (a copper chelator) and carboplatin has been carried out
      with encouraging results. This review discusses new insights into the role of
      hCtr1 in regulating copper homeostasis and explains how modulating cellular
      copper availability could influence treatment efficacy in platinum-based cancer
      chemotherapy through hCtr1 regulation.

PMID- 22962277
TI  - Overexpression of a novel biotrophy-specific Colletotrichum truncatum effector,
      CtNUDIX, in hemibiotrophic fungal phytopathogens causes incompatibility with
      their host plants.
AB  - The hemibiotrophic fungus Colletotrichum truncatum causes anthracnose disease on
      lentils and a few other grain legumes. It shows initial symptomless intracellular
      growth, where colonized host cells remain viable (biotrophy), and then switches
      to necrotrophic growth, killing the colonized host plant tissues. Here, we report
      a novel effector gene, CtNUDIX, from C. truncatum that is exclusively expressed
      during the late biotrophic phase (before the switch to necrotrophy) and elicits a
      hypersensitive response (HR)-like cell death in tobacco leaves transiently
      expressing the effector. CtNUDIX homologs, which contain a signal peptide and a
      Nudix hydrolase domain, may be unique to hemibiotrophic fungal and fungus-like
      plant pathogens. CtNUDIX lacking a signal peptide or a Nudix motif failed to
      induce cell death in tobacco. Expression of CtNUDIX:eGFP in tobacco suggested
      that the fusion protein might act on the host cell plasma membrane.
      Overexpression of CtNUDIX in C. truncatum and the rice blast pathogen,
      Magnaporthe oryzae, resulted in incompatibility with the hosts lentil and barley,
      respectively, by causing an HR-like response in infected host cells associated
      with the biotrophic invasive hyphae. These results suggest that C. truncatum and
      possibly M. oryzae elicit cell death to signal the transition from biotrophy to
      necrotrophy.

PMID- 22962279
TI  - Fe3O4 nanobelts: one-pot and template-free synthesis, magnetic property, and
      application for lithium storage.
AB  - We report on the synthesis of Fe(3)O(4) nanobelts with good magnetic properties
      and lithium storage performances by using a one-pot and template-free
      hydrothermal method with Na(2)CO(3) and FeCl(2) as the reactants. By controlling
      the amount of Na(2)CO(3), we obtained pure Fe(3)O(4) nanobelts with widths of 0.1
      2 MUm, thicknesses of about 10 nm and lengths of 20-30 MUm, showing a high aspect
      ratio. XRD and SAED patterns of the obtained sample demonstrated that the
      Fe(3)O(4) nanobelts were well crystallized. Nitrogen adsorption/desorption
      measurements showed that Fe(3)O(4) nanobelts manifested a BET surface area of
      25.04 m(2) g(-1). Further experiments demonstrated that the amount of Na(2)CO(3)
      played an important role in controlling both the morphologies and crystal
      structures of the products. The formation mechanism of Fe(3)O(4) nanobelts was
      also studied. More importantly, we found that the Fe(3)O(4) nanobelts showed
      magnetic properties with a magnetic saturation value of 77.0 emu g(-1) and
      lithium storage performances with a high initial discharge capacity of 1090 mAh
      g(-1) at a current rate of 500 mA g(-1), and a reversible capacity of 404 mAh g(
      1) retained after 60 charge/discharge cycles. These results suggest that the
      Fe(3)O(4) nanobelts might be promising for magnetic and lithium battery
      applications.

PMID- 22962278
TI  - Physiological significance of network organization in fungi.
AB  - The evolution of multicellularity has occurred in diverse lineages and in
      multiple ways among eukaryotic species. For plants and fungi, multicellular forms
      are derived from ancestors that failed to separate following cell division, thus
      retaining cytoplasmic continuity between the daughter cells. In networked
      organisms, such as filamentous fungi, cytoplasmic continuity facilitates the long
      distance transport of resources without the elaboration of a separate vascular
      system. Nutrient translocation in fungi is essential for nutrient cycling in
      ecosystems, mycorrhizal symbioses, virulence, and substrate utilization. It has
      been proposed that an interconnected mycelial network influences resource
      translocation, but the theory has not been empirically tested. Here we show, by
      using mutants that disrupt network formation in Neurospora crassa (Deltaso
      mutant, no fusion; DeltaPrm-1 mutant, ~50% fusion), that the translocation of
      labeled nutrients is adversely affected in homogeneous environments and is even
      more severely impacted in heterogeneous environments. We also show that the
      ability to share resources and genetic exchange between colonies (via hyphal
      fusion) is very limited in mature colonies, in contrast to in young colonies and
      germlings that readily share nutrients and genetic resources. The differences in
      genetic/resource sharing between young and mature colonies were associated with
      variations in colony architecture (hyphal differentiation/diameters, branching
      patterns, and angles). Thus, the ability to share resources and genetic material
      between colonies is developmentally regulated and is a function of the age of a
      colony. This study highlights the necessity of hyphal fusion for efficient
      nutrient translocation within an N. crassa colony but also shows that established
      N. crassa colonies do not share resources in a significant manner.

PMID- 22962280
TI  - Utility of lung ultrasound in predicting pulmonary and cardiac pressures.
AB  - AIMS: Quantification of linear lung ultrasound (LUS) artefacts (B-lines)
      represents a novel, non-invasive approach to assess pulmonary congestion. We
      investigated the relationship between the number of B-lines (vertical artefacts
      arising from the pleural line) and intracardiac pressures. METHODS AND RESULTS:
      Prior to scheduled right heart catheterization (RHC), 100 subjects underwent LUS
      of eight zones. A reviewer blinded to the haemodynamic data quantified the number
      of sonographic B-lines. Of 92 subjects who completed RHC, 79 had adequate LUS
      data of all zones [median age 61 years, 26 women, median left ventricular
      ejection fraction (LVEF) 58%, 35 with history of heart failure; 22 postcardiac
      transplantation]. The number of B-lines correlated with measured right atrial (r
      = 0.32), pulmonary artery diastolic (PADP) (r = 0.34), mean pulmonary artery
      (mPAP) (r = 0.43), pulmonary artery systolic (PASP) (r = 0.48) pressures, and
      pulmonary vascular resistance (PVR) (r = 0.51) (P < 0.005 for all), but not with
      pulmonary capillary wedge pressure. There was a graded association between
      tertiles of B-line number and increasing PADP, mPAP, PASP, and PVR (P for trend
      <=0.001 for all). Each additional B-line was associated with an increase in PASP
      of 1 mmHg and an increase in PVR of 0.1 Wood units. These associations remained
      robust after multivariable adjustment (P = 0.002). Assessment of two inferior
      lateral zones resulted in similar correlations to the eight-zone method.
      CONCLUSIONS: Easily obtainable, LUS may be useful in the estimation of right
      sided cardiac pressures and PVR. Further evaluation of lung ultrasound as an
      adjunct to heart failure diagnosis, monitoring, and prognosis is warranted.

PMID- 22962281
TI  - Composition and local strain mapping in Au-catalyzed axial Si/Ge nanowires.
AB  - For most applications, heterostructures in nanowires (NWs) with lattice
      mismatched materials are required and promise certain advantages thanks to
      lateral strain relaxation. The formation of Si/Ge axial heterojunctions is a
      challenging task to obtain straight, defect free and extended NWs. And the
      control of the interface will determine the future device properties. This paper
      reports the growth and analysis of NWs consisting of an axial Si/Ge
      heterostructure grown by a vapor-liquid-solid process. The composition gradient
      and the strain distribution at the heterointerface were measured by advanced
      quantitative electron microscopy methods with a resolution at the nanometer
      scale. The transition from pure Ge to pure Si shows an exponential slope with a
      transition width of 21 nm for a NW diameter of 31 nm. Although diffuse, the
      heterointerface makes possible strain engineering along the axis of the NW. The
      interface is dislocation-free and a tensile out-of-plane strain is noticeable in
      the Ge section of the NW, indicating a lattice accommodation. Experimental
      results were compared to finite element calculations.

PMID- 22962282
TI  - Semiconducting and conducting transition of covalent-organic polymers induced by
      defects.
AB  - The chemical doping method is often adopted to obtain metal-free conducting
      materials. To date, it is still a great challenge to controllably prepare metal
      free semiconducting and conducting materials by tuning the inherent structure of
      a material. In this work, a class of novel one-dimensional (1D) covalent-organic
      polymer (COP) has been designed, whose cross-sections are triangular, tetragonal,
      pentagonal and hexagonal, and their electronic properties are explored. The
      tetragonal 1D COP exhibits unique phenomena in electronic properties, i.e. the
      tetragonal COPs with mono- or trilayer defects (odd defects) show semiconducting
      properties, while they become conductors for the two cases of non- or bilayer
      defects (even defects). This observation indicates that they comply with the
      characteristics of semiconducting and conducting switches induced by the odd-even
      defects. Therefore, we infer that for the tetragonal configuration, the odd-even
      defects could potentially manipulate the electrical behavior of the COP material.
      The discovery provides a new direction for the targeted synthesis of
      semiconducting and conducting materials by tuning the inherent structure of
      materials, which is entirely different from the chemical doping method yielding
      metal-free conducting materials.

PMID- 22962283
TI  - Contributions of treatment and lifestyle to declining CVD mortality: why have CVD
      mortality rates declined so much since the 1960s?
AB  - Developed countries have enjoyed substantial falls in cardiovascular disease
      (CVD) mortality. However, low and middle income countries are drowning in a
      rising tide of CVD and other non-communicable diseases. Current and future trends
      in CVD mortality will therefore require increasing attention in the 21st century.
      The success of clinical cardiology in providing evidence-based cost-effective
      treatments should be celebrated. However, the growing understanding of CVD
      mortality trends highlights the crucial role of tobacco, diet, alcohol and
      inactivity as key drivers. Pro-active public health approaches focused on
      'upstream' population-wide policies are increasingly recognised as being
      potentially powerful, rapid, equitable and cost-saving. However, the future
      political challenges could be substantial.

PMID- 22962284
TI  - Prevalence of significant tricuspid regurgitation in patients with successful
      percutaneous mitral valvuloplasty for mitral stenosis: results from 12 years'
      follow-up of one centre prospective registry.
AB  - BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is an attractive therapeutic
      option for mitral stenosis (MS). OBJECTIVE: To investigate the incidence and
      development of tricuspid regurgitation (TR) long after successful PMV.   DESIGN,
      PATIENTS AND INTERVENTIONS:  A prospective cohort of 299 patients with
      symptomatic MS who underwent successful PMV as first-line treatment between 1988
      and 2010. SETTING: One tertiary university hospital. MAIN OUTCOME MEASURES:
      Significant TR, defined as a grade >=3 on echocardiographic analysis. RESULTS:
      Although most TR regressed in these patients immediately after the procedure, 56
      patients developed significant TR during follow-up (median 12 years, IQR 8.0-18.0
      years). The cumulative incidence of significant TR increased time-dependently
      (9.4%, 19.8% and 35.2% at 8, 12 and 18 years of follow-up, respectively). Atrial
      fibrillation (AF) and TR grade >=2 before PMV were found to be independent
      predictors of significant TR (HR (95% CI) 3.049 (1.169 to 7.949) and 3.016 (1.303
      to 6.982), p=0.023 and 0.010 for pre-PMV AF and pre-PMV TR grade >=2,
      respectively). Even after, exclusion of patients with significant TR at baseline,
      pre-PMV TR grade >=2 and AF remained important factors of de novo TR development.
      Mitral valve restenosis was also associated with late significant TR development.
      CONCLUSIONS: Significant TR after successful PMV in patients with MS is not
      uncommon long after PMV. TR development is closely associated with mitral valve
      restenosis. More attention should be paid during long-term follow-up to TR
      development in patients with MS who have significant pre-PMV TR and/or AF.

PMID- 22962285
TI  - Vagal stimulation for the treatment of heart failure: a translational success
      story.

PMID- 22962286
TI  - Atomic force microscopy to characterize binding properties of alpha7-containing
      nicotinic acetylcholine receptors on neurokinin-1 receptor-expressing medullary
      respiratory neurons.
AB  - In the present study, we used atomic force microscopy (AFM) to examine the ligand
      binding properties of alpha7-containing nicotinic acetylcholine receptors
      (nAChRs) expressed on neurons from the ventral respiratory group. We also
      determined the effect of acute and prolonged exposure to nicotine on the binding
      probability of nAChRs. Neurons from neonatal (postnatal day 5-10) and juvenile
      rats (3-4 weeks old) were cultured. Internalization of Alexa Fluor 488-conjugated
      substance P was used to identify respiratory neurons that expressed the
      neurokinin-1 receptor (NK1-R), a recognized marker of ventral respiratory group
      neurons. To assess functional changes in nAChRs, AFM probes conjugated with anti
      alpha7 subunit nAChR antibody were used to interact cyclically with the surface
      of the soma of NK1-R-positive neurons. Measurements were made of the frequency of
      antibody adhesion to the alpha7 receptor subunit and of the detachment forces
      between the membrane-attached receptor and the AFM probe tip. Addition of alpha
      bungarotoxin (a specific antagonist of alpha7 subunit-containing nAChRs) to the
      cell bath produced a 69% reduction in binding to the alpha7 subunit (P < 0.05, n
      = 10), supporting specificity of binding. Acute exposure to nicotine (1 MUM added
      to culture media) produced an 80% reduction in nAChR antibody binding to the
      alpha7 subunit (P < 0.05, n = 9). Prolonged incubation (72 h) of the cell culture
      in nicotine significantly reduced alpha7 binding in a concentration-dependent
      manner. Collectively, these findings demonstrate that AFM is a sensitive tool for
      assessment of functional changes in nAChRs expressed on the surface of living NK1
      R-expressing medullary neurons. Moreover, these data demonstrate that nicotine
      exposure decreases the binding probability of alpha7 subunit-containing nAChRs.

PMID- 22962287
TI  - Intense intermittent exercise provides weak stimulus for vascular endothelial
      growth factor secretion and capillary growth in skeletal muscle.
AB  - The effect of acute intense intermittent exercise compared with moderate
      intensity exercise on angiogenic factors and the effect of 4 weeks of intense
      intermittent training on capillary growth were examined in nine healthy young
      men, preconditioned by moderate-intensity endurance training. The intense
      training consisted of 24 bouts of 1 min cycling at an initial work rate of 316 +/
      19 W (~117% of pretraining maximal oxygen uptake), performed three times per
      week. Skeletal muscle biopsies and muscle microdialysates were obtained from the
      vastus lateralis before, during and after acute exercise performed at either
      moderate or high intensity. Comparison of the response in angiogenic factors to
      acute moderate- versus high-intensity exercise, performed prior to the intense
      training intervention, revealed that intense exercise resulted in a markedly
      lower (~60%; P < 0.05) increase in interstitial vascular endothelial growth
      factor than did moderate-intensity exercise. Muscle interstitial fluid obtained
      during moderate-intensity exercise increased endothelial cell proliferation in
      vitro more than interstitial fluid obtained during intense exercise (sixfold
      versus 2.5-fold, respectively; P < 0.05). The 4 weeks of high-intensity training
      did not lead to an increased capillarization in the muscle but abolished the
      exercise-induced increase in mRNA for several angiogenic factors, increased the
      protein levels of endothelial nitric oxide synthase, lowered the protein levels
      of thrombospondin-1 in muscle but increased the interstitial protein levels of
      thrombospondin-1. We conclude that intense intermittent exercise provides a weak
      stimulus for vascular endothelial growth factor secretion and endothelial cell
      proliferation and that intense intermittent training does not induce a sufficient
      angiogenic stimulus to induce capillary growth in muscle previously conditioned
      by moderate-intensity exercise.

PMID- 22962288
TI  - Validation of the Knee Injury and Osteoarthritis Outcome Score subscales for
      patients with articular cartilage lesions of the knee.
AB  - BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) assesses
      acute and chronic knee injuries or early-onset osteoarthritis in young, active
      patients. The United States Food and Drug Administration guidelines recommend
      that patient-reported outcome instruments used to support clinical trial label
      claims should demonstrate content validity using patient input and have
      acceptable psychometric properties in the target population. To use the KOOS
      subscales in safety and efficacy trials assessing new treatments for patients
      with articular cartilage lesions, additional validation work, using input from
      patients with articular cartilage lesions, was necessary. PURPOSE: Qualitative
      and quantitative evaluations of the KOOS subscales' validity among patients with
      articular cartilage lesions were conducted to support their use as clinically
      meaningful end points in clinical trials. STUDY DESIGN: Cohort study (diagnosis);
      Level of evidence, 2. METHODS: For qualitative analysis, cognitive interviews
      involving concept elicitation and cognitive debriefing with the KOOS items were
      conducted with 15 participants aged 25 to 52 years. Participants either were
      candidates for cartilage repair or had undergone cartilage repair 6 months or
      more before the study. For the quantitative analysis, a psychometric evaluation
      of the KOOS was conducted with clinical trial data from 54 patients, aged 18 to
      55 years, evaluating the Cartilage Autograft Implantation System in the United
      States (n = 29) and the European Union (n = 25). Data were collected before
      surgery and at 7 postsurgical visits up to 12 months. Internal consistency and
      test-retest reliability, construct validity, responsiveness, and estimates of the
      minimal detectable change (MDC) were assessed. Test-retest reliability was
      assessed using data from months 2 and 3 on a subset of stable patients. RESULTS:
      Qualitative research confirmed that concepts measured on the KOOS are important
      to patients with articular cartilage lesions. Most participants reported the KOOS
      was comprehensive and appropriate. In the quantitative research, KOOS subscales
      showed excellent internal consistency reliability (range, .74-.97 at baseline)
      and test-retest reliability (range, .78-.82). Construct validity results
      supported hypothesized relationships, with significant correlations (r >= .50) in
      the expected directions. Responsiveness analyses demonstrated excellent
      sensitivity to change; standardized response means ranged from 0.8 to 1.2, and
      MDC estimates ranged from 7.4 to 12.1. CONCLUSION: The study results support the
      use of the KOOS subscales among patients with articular cartilage lesions.

PMID- 22962289
TI  - Reliability of tunnel measurements and the quadrant method using fluoroscopic
      radiographs after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction tunnel placement is
      often evaluated by radiographs. This study examines the interobserver reliability
      of various radiographic measurements of ACL tunnels. HYPOTHESIS: When ideal
      radiographic views are obtained, the interobserver reliability of the
      measurements among experienced surgeons would be good to excellent. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Tunnels for single-bundle ACL
      reconstruction were drilled and filled with metal interference screws or a tibial
      reamer on 73 cadaveric knees. Ideal fluoroscopic radiographs were obtained. Three
      independent reviewers performed 18 measurements including a modification of the
      grid method. For the grid method analysis, reviewers fit a 16 * 12 grid to the
      lateral knee radiograph, and the center of the femoral tunnel was marked.
      Interobserver reliability of the measurements was performed using intraclass
      correlation coefficients (ICCs). A precision grouping analysis was performed for
      the grid measurements to calculate the mean radius and standard deviation
      grouping distances. RESULTS: The ICCs were excellent (>.75) for the tibial tunnel
      angles and tunnel measurements, the clock face measurement, and the Aglietti et
      al and Jonsson et al measurements. The ICCs were good (.4-.75) for an estimation
      of graft impingement, Harner et al measurements, and notch height. The mean
      radius for grid measurements was 0.6 +/- 0.4 units (range, 0-2.36 units), with
      each unit being 1 box in the 16 * 12 grid. When a circle was constructed with a
      1.3-unit radius, 95% of the 3 surgeons' measurements would be included in the
      area of that circle. CONCLUSION: Reliability of ACL tunnel measurements was good
      to excellent under ideal circumstances for the majority of measurements. The
      modified grid method demonstrated very acceptable reliability. CLINICAL
      RELEVANCE: Measurements with good to excellent reliability can be used to
      evaluate ACL tunnel placement when ideal radiographic views are obtained.

PMID- 22962291
TI  - Anatomic suture anchor versus the Brostrom technique for anterior talofibular
      ligament repair: a biomechanical comparison.
AB  - BACKGROUND: Despite the popularity of the Brostrom procedure for secondary repair
      of chronic lateral ankle instability, there have been no biomechanical studies
      reporting on the strength of this secondary repair method, whether using suture
      fixation or suture anchors. HYPOTHESIS: The purpose of our study was to perform a
      biomechanical comparison of the ultimate load to failure and stiffness of the
      traditional Brostrom technique using only a suture repair compared with a suture
      anchor repair of the anterior talofibular ligament (ATFL) at time zero. We
      believed that fixation strength of the suture anchor repair would be closer to
      the strength of the native ligament and allow more aggressive rehabilitation.
      STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-four fresh-frozen
      cadaveric ankles were randomly divided into 4 groups of 6 specimens. One group
      was an intact control group, and the other groups consisted of the traditional
      Brostrom and 2 suture anchor modifications (suture anchors in talus or fibula) of
      the Brostrom procedure. The specimens were loaded to failure to determine the
      strength and stiffness of each construct. RESULTS: In load-to-failure testing,
      ultimate failure loads of the Brostrom (68.2 +/- 27.8 N; P = .013), suture anchor
      fibula (79.2 +/- 34.3 N; P = .037), and suture anchor talus (75.3 +/- 45.6 N; P =
      .027) repairs were significantly lower than that of the intact (160.9 +/- 72.2 N)
      ATFL group. Stiffness of the Brostrom (6.0 +/- 2.5 N/mm; P = .02), suture anchor
      fibula (6.8 N/mm +/- 2.7; P = .05), and suture anchor talus (6.6 N/mm +/- 4.0; P
      = .04) repairs were significantly lower than that of the intact (12.4 N/mm +/-
      4.1 N/mm) ATFL group. The 3 repair groups were not significantly different from
      each other, but all 3 were substantially lower in strength and stiffness when
      compared to the intact ATFL. CONCLUSION: The use of suture anchors to repair the
      ATFL produces a repair that can withstand loads to failure similar to the suture
      only Brostrom repair. However, all 3 repair groups were much weaker than the
      intact, uninjured ATFL. CLINICAL RELEVANCE: Biomechanically, the results show
      that both suture anchor and direct suture repair of the ATFL provide similar
      strength and stiffness. Unfortunately, these methods provide less than half the
      strength and stiffness of the native ATFL at time zero. As a result, regardless
      of the repair method, it is necessary to sufficiently protect the repair to avoid
      premature failure.

PMID- 22962290
TI  - A pair-matched comparison of return to pivoting sports at 1 year in anterior
      cruciate ligament-injured patients after a nonoperative versus an operative
      treatment course.
AB  - BACKGROUND: Patients usually return to pivoting sports between 6 months and 1
      year after anterior cruciate ligament (ACL) reconstruction, but no matched study
      has so far examined 1-year return to sport rates in nonoperatively and
      operatively treated ACL-injured patients. HYPOTHESIS: Anterior cruciate ligament
      injured patients following a nonoperative treatment course, including
      recommendation of activity modification, will have lower return to pivoting sport
      rates than operatively treated patients 1 year after baseline testing/surgery,
      when matched by preinjury sports activity, age, and sex. STUDY DESIGN: Cohort
      study; level of evidence, 3. METHODS: Sixty-nine nonoperatively treated ACL
      injured patients were pair-matched with 69 operatively treated patients (n =
      138), based on specific preinjury sport, age, and sex. Nonoperatively treated
      patients were recommended not to return to level I sports. Patients were defined
      as nonoperatively or operatively treated according to their status at follow-up.
      The baseline and follow-up testing included registration of sports participation,
      KT-1000 arthrometer measurements, 4 hop tests, and patient-reported outcome
      measures. McNemars test and paired t tests or Wilcoxon test were used to compare
      outcomes of nonoperatively and operatively treated patients. RESULTS: No
      significant baseline differences were found. At 12.9 +/- 1.2 months (mean +/-
      standard deviation) after baseline testing (nonoperative) and 12.7 +/- 1.2 months
      after surgery (operative), there was no significant difference in overall return
      to sport rates (nonoperative: 68.1%, operative: 68.1%, P = 1.00), or in return to
      level I sport rates (nonoperative: 54.8%, operative: 61.9%, P = .66).
      Nonoperatively treated patients who participated in level I sports before injury
      had a significantly lower return to sport rate (54.8%) than nonoperatively
      treated patients who participated in level II sports (88.9%, P = .003). The
      nonoperatively treated patients had significantly higher knee joint laxity, but
      significantly better hop test limb symmetry indexes, Knee Outcome Survey
      Activities of Daily Living scores, and International Knee Documentation Committee
      Subjective Knee Form 2000 scores. None of the functional differences was larger
      than the smallest detectable difference. CONCLUSION: Anterior cruciate ligament
      injured patients following a nonoperative treatment course, including
      recommendations of activity modifications, and operatively treated patients did
      not have significantly different rates of returning to pivoting sports after 1
      year in this pair-matched cohort study. Clinicians should be aware of a
      potentially high level of noncompliance to recommendations of activity
      modifications. Although these results show that it is possible for nonoperatively
      treated patients to return to sport after rehabilitation, future follow-ups are
      needed to examine whether these patients maintain sports participation over time,
      and what long-term consequences they may suffer regarding subsequent injuries and
      knee osteoarthritis.

PMID- 22962292
TI  - Age-related differences in medial patellofemoral ligament injury patterns in
      traumatic patellar dislocation: case series of 50 surgically treated children and
      adolescents.
AB  - BACKGROUND: Complete rupture of the medial patellofemoral ligament (MPFL) during
      traumatic patellar dislocation may contribute to further patellar instability. As
      there is still no consensus regarding indications for treatment of such injuries,
      data on exact localization and extent of tear may influence the treatment
      decisions. PURPOSE: Analysis of the patterns and the age-related differences in
      the distribution of medial patellofemoral ligament injury during traumatic
      patellar dislocation in children and adolescents. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Fifty consecutive patients aged 10.5 to 17.5 years
      were operated on for injuries after a first episode of traumatic patellar
      dislocation. The indications for surgery were osteochondral fracture and/or
      complete MPFL tear. Medial patellofemoral ligament injuries were assessed
      preoperatively by sonography and then verified at surgery. To assess the
      influence of skeletal maturity on the injury pattern, the cohort was subdivided
      into 2 subgroups: skeletally immature and skeletally mature. Distribution of MPFL
      injuries in both groups was compared. RESULTS: Medial patellofemoral ligament
      injury was present at surgery in 94% of cases, most commonly at the patellar
      attachment (66%), followed by mid-fibers (50%) and femoral attachment (32%). In
      46%, it occurred in more than 1 localization. Based on functional status of the
      ligament during dynamic ultrasound examination, 2 types of injury were
      distinguished: complete and partial rupture. Eighteen of 21 complete ruptures
      were localized at the patellar attachment, and all but 1 case had a form of the
      avulsion fracture. Age-related analysis revealed these differences in the
      incidence of MPFL injury in all 3 localizations comparing skeletally immature
      with skeletally mature patients: 79% vs 54% at the patellar attachment, 46% vs
      54% at the mid-fiber region, and 33% vs 31% at the femoral attachment.
      Nevertheless, the only statistically significant difference was the higher
      incidence of patellar attachment injury in the skeletally immature group (P =
      .029). Sonography demonstrated more than 90% accuracy and predictive value in
      assessing pathoanatomy as well as the functional status of the medial
      patellofemoral ligament. CONCLUSION: Medial patellofemoral ligament injury
      patterns vary in skeletally immature patients compared with skeletally mature
      patients. Sonography proved high reliability as a diagnostic tool in traumatic
      patellar dislocation.

PMID- 22962293
TI  - Investigation of the preservation of the fluid seal effect in the repaired,
      partially resected, and reconstructed acetabular labrum in a cadaveric hip model.
AB  - BACKGROUND: Debate exists on whether hip labral tears should be surgically
      repaired, partially resected, or reconstructed. Furthermore, limited data exist
      regarding the fluid seal properties of hip labrum repair and/or reconstruction
      with iliotibial band autograft when compared with the labrum-intact condition. 
      Hypothesis/ PURPOSE: The purpose of this study was to investigate the fluid seal
      properties of hip labral repair and reconstruction techniques. We hypothesized
      that hip labral repair preserves the acetabular labral fluid seal greater than
      labral tear, partial-resection, and reconstruction conditions. STUDY DESIGN:
      Controlled laboratory study. METHODS: Six human cadaveric hemipelvises were
      dissected of all soft tissue, leaving the hip capsule intact. Fluid efflux was
      measured under 5 conditions using a custom fluid infusion device: (1) hip labrum
      intact, (2) labral tear, (3) labral repair with suture anchors, (4) partial
      labral resection, and (5) labral reconstruction using ipsilateral iliotibial band
      autograft. Joint fluid expression was measured as flow rate under 3 different
      pressure settings (2, 3, and 4 psi). Statistical differences between conditions
      were assessed using 2-way, repeated-measures analysis of variance. The Student
      Newman-Keuls (SNK) multiple comparison test was used to determine differences
      between levels. RESULTS: There was a significant increase in fluid efflux with a
      simulated labral tear (0.54 +/- 0.3 mL/sec) when compared with the intact hip
      labrum condition (0.006 +/- 0.008 mL/sec, P < .05). The labrum-repaired condition
      (0.21 +/- 0.2 mL/sec) demonstrated significantly less fluid efflux when compared
      with the labral-tear condition. Hip labral repair significantly prevented greater
      fluid efflux when compared with partial labral resection (0.60 +/- 0.4 mL/sec)
      and reconstruction with iliotibial band autograft (0.54 +/- 0.3 mL/sec; P < .05).
      Labral repair did not preserve fluid efflux as effectively as in the labrum
      intact condition (0.21 +/- 0.2 > 0.006 +/- 0.008 mL/sec; P < .05). There was no
      difference observed in fluid efflux between the labral reconstruction, tear, or
      resection conditions (P > .05). CONCLUSION: In this human cadaveric model, hip
      labral repair outperforms partial labral resection and reconstruction in
      preserving the joint fluid seal; however labral repair does not restore fluid
      seal characteristics as effectively as in the labrum-intact condition. CLINICAL
      RELEVANCE: Further prospective studies are needed to determine whether hip labral
      repair outperforms partial labral resection and/or reconstruction in clinical
      practice.

PMID- 22962294
TI  - Clinical and second-look arthroscopic study comparing 2 tibial landmarks for
      tunnel insertions during double-bundle ACL reconstruction with a minimum 2-year
      follow-up.
AB  - BACKGROUND: Few studies have reported the clinical results of tibial tunnel
      placement during double-bundle anterior cruciate ligament (ACL) reconstruction.
      It is important to recognize arthroscopic tibial landmarks during this procedure.
      HYPOTHESIS: During arthroscopic double-bundle ACL reconstruction, anterior tibial
      landmarks such as the intermeniscal (transverse) ligament and the Parsons knob
      for the anteromedial (AM) tunnel provide better knee stability and clinical
      outcomes than do posterior tibial landmarks such as the fovea anterior to the
      tibial intertubercle ridge for the posterolateral (PL) tunnel. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: A total of 121 patients underwent
      primary unilateral double-bundle ACL reconstructions using autogenous medial
      hamstring tendons. Fifty-nine patients from December 2008 through July 2009
      underwent reconstructions using posterior tibial landmarks (PL group), and 62
      patients from August 2009 through February 2010 underwent reconstructions using
      anterior tibial landmarks (AM group). Forty-seven patients (follow-up rate,
      79.7%) in the PL group and 52 patients (follow-up rate, 83.9%) in the AM group
      underwent second-look arthroscopy and clinical evaluations under anesthesia at 1
      year postoperatively and 3-dimensional computed tomography (3-D CT) evaluations
      at 3 weeks postoperatively. RESULTS: Lachman test results indicated no
      significant differences, and pivot-shift test results were significantly lower in
      the AM group (P = .007). Mean side-to-side differences using the Telos device at
      130 N were significantly lower in the AM group (1.4 +/- 1.6 mm) compared with the
      PL group (2.4 +/- 2.5 mm) (P = .012). Results for lack of extension were not
      significantly different, while those for lack of flexion were significantly
      better in the AM group than in the PL group (P = .036). No significant
      differences were observed in the Lysholm scores between the groups. In
      measurements of the tibial tunnel position by 3-D CT, with regard to
      anteroposterior depth, the AM bundle of the PL group was 41.6% +/- 7.4% and the
      AM group was 29.1% +/- 5.3% (P < .001), and the PL bundle of the PL group was
      55.6% +/- 7.7% and the AM group was 46.4% +/- 5.8% (P < .001). No significant
      differences were found in mediolateral width. In second-look arthroscopy, there
      were significant differences with respect to the synovial cover with regard to
      the AM bundle (P = .024). CONCLUSION: Patients in the AM group showed better knee
      stability and range of motion than those in the PL group. Transverse ligaments
      and Parsons knobs proved to be useful landmarks during ACL reconstruction.

PMID- 22962295
TI  - Quantifying clinically significant change: a brief review of methods and
      presentation of a hybrid approach.
AB  - Treatment outcome researchers in orthopaedics frequently report only tests of
      statistical significance between group means to evaluate the effectiveness of a
      given intervention. Although important in establishing that mean differences are
      not caused by chance, these methods do not reflect the extent to which an
      intervention produces improvements that are meaningful and represent a return to
      health. This is an issue that is often of great interest to patients and
      clinicians. Other methods use a percentage change in an outcome measure (eg, 25%
      reduction in pain score) to classify treatment responders but often do not
      indicate whether the treatment restored a patient to normal. Researchers have
      developed several indices that provide a metric for statistically defining the
      amount of change that patients consider to be important. In this article, we
      focus on the concept of "clinical significance" and the different methods that
      have been developed to define clinically significant change using statistics. We
      then present a hybrid method that can classify whether a patient has returned to
      normal function. We apply this method to real patient data to illustrate its use
      with different outcome instruments commonly used in orthopaedic sports medicine.
      We advocate that the addition of these methods to reports from clinical outcome
      studies can deepen our understanding of the impact of interventions on patients'
      lives.

PMID- 22962296
TI  - The Swedish National Anterior Cruciate Ligament Register: a report on baseline
      variables and outcomes of surgery for almost 18,000 patients.
AB  - BACKGROUND: The Swedish National Anterior Cruciate Ligament Register provides an
      opportunity for quality surveillance and research. PURPOSE: The primary objective
      was to recognize factors associated with a poorer outcome at an early stage.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Registrations are made
      using a web-based protocol with 2 parts: a patient-based section with self
      reported outcome scores and a surgeon-based section, where factors such as cause
      of injury, previous surgery, time between injury and reconstruction, graft
      selection, fixation technique, and concomitant injuries are reported. The self
      reported outcome scores are registered preoperatively and at 1, 2, and 5 years.
      RESULTS: Approximately 90% of all anterior cruciate ligament (ACL)
      reconstructions performed annually in Sweden are reported in the register.
      Registrations during the period 2005-2010 were included (n = 17,794). After
      excluding multiligament reconstructions and reoperations, the male:female ratio
      was 57.5:42.5 for both primary (n = 15,387) and revision (n = 964) surgery. The
      cause of injury was soccer in approximately half the male patients and in one
      third of the female patients. All subscales of the Knee injury and Osteoarthritis
      Outcome Score (KOOS) were significantly improved 1, 2, and 5 years
      postoperatively in patients undergoing primary reconstructions. In terms of the
      KOOS, revisions did significantly less well than primary reconstructions on all
      follow-up occasions, and smokers fared significantly less well than nonsmokers
      both preoperatively and at 2 years. Patients who had concomitant meniscal or
      chondral injuries at reconstruction did significantly less well preoperatively
      and at 1 year in terms of most KOOS subscales compared with patients with no such
      injuries. At 5 years, a significant difference was only found in terms of the
      sport/recreation subscale. Double-bundle reconstructions revealed no significant
      differences in terms of all the KOOS subscales at 2 years compared with single
      bundle reconstructions (114 double-bundle vs 5109 single-bundle). During a 5-year
      period, 9.1% (contralateral, 5.0%; revision, 4.1%) of the patients underwent a
      contralateral ACL reconstruction or revision reconstruction of the index knee.
      The corresponding figure for 15- to 18-year-old female soccer players was 22.0%.
      CONCLUSION: Primary ACL reconstruction significantly improves all the subscales
      of the KOOS. Young female soccer players run a major risk of reinjuring their ACL
      or injuring the contralateral ACL; revision ACL reconstructions do less well than
      primary reconstructions, and smokers do less well than nonsmokers.

PMID- 22962297
TI  - Qualitative and quantitative anatomic analysis of the posterior root attachments
      of the medial and lateral menisci.
AB  - BACKGROUND: The clinical importance of the meniscal posterior root attachments
      has been recently reported by both biomechanical and clinical studies. Although
      several studies have been performed to evaluate surgical techniques, there have
      been few studies on the quantitative arthroscopically pertinent anatomy of the
      posterior meniscal root attachments. HYPOTHESIS: The posterior root attachments
      of the medial and lateral menisci are consistent among specimens, and repeatable
      quantitative measurements using arthroscopically pertinent landmarks are
      achievable. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve
      nonpaired, fresh-frozen cadaveric knees were used. The positions of the posterior
      root attachments of the medial and lateral menisci were identified, and 3
      dimensional measurements to arthroscopically pertinent landmarks were performed
      using a coordinate measuring system. RESULTS: The direct distance (+/-standard
      error of the mean) between the medial tibial eminence apex and the medial
      meniscus posterior root attachment center was 11.5 (+/-0.9) mm. When split into
      directional components along the knee's main axes, the medial meniscus posterior
      root attachment center was 9.6 (+/-0.8) mm posterior and 0.7 (+/-0.4) mm lateral
      along the bony surface from the medial tibial eminence apex. It was located 3.5
      (+/-0.4) mm lateral from the medial articular cartilage inflection point and
      directly 8.2 (+/-0.7) mm from the nearest tibial attachment margin of the
      posterior cruciate ligament. The direct distance between the lateral tibial
      eminence apex and the lateral meniscus posterior root attachment center was 5.3
      (+/-0.3) mm. When it was split into directional components using the knee's main
      axes, the lateral meniscus posterior root attachment center was 4.2 (+/-0.4) mm
      medial and 1.5 (+/-0.7) mm posterior from the lateral tibial eminence apex. The
      lateral meniscus posterior root attachment center was located 4.3 (+/-0.5) mm
      medial from the nearest articular cartilage margin and directly 12.7 (+/-1.1) mm
      from the nearest margin of the tibial attachment of the posterior cruciate
      ligament. CONCLUSION: This quantitative study reproducibly identified the
      posterior root attachment centers of the medial and lateral menisci in relation
      to arthroscopically pertinent landmarks and guidelines. CLINICAL RELEVANCE: These
      data can be directly applied to assist in anatomic meniscal root repairs.

PMID- 22962298
TI  - Repair of meniscal tears associated with tibial plateau fractures: a review of 15
      cases.
AB  - BACKGROUND: Tibial plateau fractures are frequently associated with meniscal
      tears. Little is known about the results of meniscal repair in this group of
      patients. PURPOSE: To determine the results of repair of meniscal tears found
      during arthroscopically assisted reduction and internal fixation (ARIF) of tibial
      plateau fractures. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In a
      cohort of 51 tibial plateau fractures treated with ARIF, 15 associated meniscal
      tears (15 knees) in 14 patients were repaired. There were 12 peripheral
      longitudinal tears of the lateral meniscus, 1 longitudinal peripheral tear of the
      medial meniscus, 1 full-thickness radial tear of the lateral meniscus, and 1 bird
      beak tear of the lateral meniscus. Repairs were performed using an outside-in
      technique for the anterior horn and all-inside repair for the body and posterior
      horn lesions. Mean (SD) age at operation was 47.3 (14.0) years. Patients were
      followed for a mean (SD) of 4.83 (1.01) years and evaluated using the Rasmussen,
      Honkonen, Lysholm, Tegner, and International Knee Documentation Committee (IKDC)
      scores. A second-look arthroscopy was performed in 13 knees a mean (SD) of 14.2
      (10.1) months after the initial surgery. RESULTS: The mean (SD) Rasmussen score
      was 29.1 (0.96). Thirteen of 15 patients scored good or excellent results in all
      Honkonen sections. The mean (SD) Lysholm score was 88.6 (12.4). The mean (SD)
      IKDC score was 79.3 (19.3). There was a small decrease of the activity level
      according to the Tegner score when compared with the preoperative situation (1.20
      [1.82], P = .022). There were not any meniscal symptoms in any case. Of the 13
      menisci evaluated with second-look arthroscopy, 12 had healed completely and a
      radial tear had healed partially in the vascular zone. In one of the cases that
      healed, a new tear was found in a different location. CONCLUSION: Meniscal repair
      of tears associated with tibial plateau fractures has good results. All patients
      had good or excellent clinical results. Second-look arthroscopy confirmed
      complete healing in 92% of meniscal tears when performed.

PMID- 22962299
TI  - An alpha-helical C-terminal tail segment of the skeletal L-type Ca2+ channel
      beta1a subunit activates ryanodine receptor type 1 via a hydrophobic surface.
AB  - Excitation-contraction (EC) coupling in skeletal muscle depends on protein
      interactions between the transverse tubule dihydropyridine receptor (DHPR)
      voltage sensor and intracellular ryanodine receptor (RyR1) calcium release
      channel. We present novel data showing that the C-terminal 35 residues of the
      beta(1a) subunit adopt a nascent alpha-helix in which 3 hydrophobic residues
      align to form a hydrophobic surface that binds to RyR1 isolated from rabbit
      skeletal muscle. Mutation of the hydrophobic residues (L496, L500, W503) in
      peptide beta(1a)V490-M524, corresponding to the C-terminal 35 residues of
      beta(1a), reduced peptide binding to RyR1 to 15.2 +/- 7.1% and prevented the 2.9
      +/- 0.2-fold activation of RyR1 by 10 nM wild-type peptide. An upstream
      hydrophobic heptad repeat implicated in beta(1a) binding to RyR1 does not
      contribute to RyR1 activation. Wild-type beta(1a)A474-A508 peptide (10 nM),
      containing heptad repeat and hydrophobic surface residues, increased RyR1
      activity by 2.3 +/- 0.2- and 2.2 +/- 0.3-fold after mutation of the heptad repeat
      residues. We conclude that specific hydrophobic surface residues in the 35
      residue beta(1a) C-terminus bind to RyR1 and increase channel activity in lipid
      bilayers and thus may support skeletal EC coupling.

PMID- 22962300
TI  - Chromosome-specific accumulation of aneuploidy in the aging mouse brain.
AB  - Chromosomal aneuploidy, the gain or loss of whole chromosomes, is a hallmark of
      pathological conditions and a causal factor of birth defects and cancer. A number
      of studies indicate that aneuploid cells are present at a high frequency in the
      brain of mice and humans, suggesting that mosaic aneuploidies are compatible with
      normal brain function and prompting the question about their consequences. To
      explore the possible contribution of aneuploidy to functional decline and loss of
      cognitive functions during aging, we used a quantitative, dual-labeling
      interphase-fluorescence in situ hybridization approach to compare aneuploidy
      levels of chromosomes 1, 7, 14, 15, 16, 18, 19 and Y in the cerebral cortex of 4-
      and 28-month-old mice. We show that aneuploidy accumulates with age in a
      chromosome-specific manner, with chromosomes 7, 18 and Y most severely affected,
      i.e. up to 9.8% of non-neuronal brain nuclei in 28-month-old animals for
      chromosome 18. While at early age, both neuronal and glial cells are affected
      equally, the age-related increase was limited to the non-neuronal nuclei. No age
      related increase in aneuploidy was observed in the cerebellum or in the spleen of
      the same animals. Extrapolating the average frequencies of aneuploidy from the
      average over 8 chromosomes to all 20 mouse chromosomes would indicate an almost
      50% aneuploidy frequency in aged mouse brain. Such high levels of genome
      instability could well be a factor in age-related neurodegeneration.

PMID- 22962301
TI  - Somatic NF1 inactivation is a frequent event in sporadic pheochromocytoma.
AB  - Germline mutations in the RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127, NF1
      or VHL genes are identified in about 30% of patients with pheochromocytoma or
      paraganglioma and somatic mutations in RET, VHL or MAX genes are reported in 17%
      of sporadic tumors. In the present study, using mutation screening of the NF1
      gene, mapping of chromosome aberrations by single nucleotide polymorphism (SNP)
      array, microarray-based expression profiling and immunohistochemistry (IHC), we
      addressed the implication of NF1 somatic alterations in pheochromocytomas and
      paragangliomas. We studied 53 sporadic tumors, selected because of their
      classification with RET/NF1/TMEM127-related tumors by genome wide expression
      studies, as well as a second set of 11 independent tumors selected on their low
      individual levels of NF1 expression evaluated by microarray. Direct sequencing of
      the NF1 gene in tumor DNA identified the presence of an inactivating NF1 somatic
      mutation in 41% (25/61) of analyzed sporadic tumors, associated with loss of the
      wild-type allele in 84% (21/25) of cases. Gene expression signature of NF1
      related tumors highlighted the downregulation of NF1 and the major overexpression
      of SOX9. Among the second set of 11 tumors, two sporadic tumors carried somatic
      mutations in NF1 as well as in another susceptibility gene. These new findings
      suggest that NF1 loss of function is a frequent event in the tumorigenesis of
      sporadic pheochromocytoma and strengthen the new concept of molecular-based
      targeted therapy for pheochromocytoma or paraganglioma.

PMID- 22962302
TI  - Cytogeography and genome size variation in the Claytonia perfoliata
      (Portulacaceae) polyploid complex.
AB  - BACKGROUND AND AIMS: Genome duplication is a central process in plant evolution
      and contributes to patterns of variation in genome size within and among
      lineages. Studies that combine cytogeography with genome size measurements
      contribute to our basic knowledge of cytotype distributions and their
      associations with variation in genome size. METHODS: Ploidy and genome size were
      assessed with direct chromosome counts and flow cytometry for 78 populations
      within the Claytonia perfoliata complex, comprised of three diploid taxa with
      numerous polyploids that range to the decaploid level. The relationship between
      genome size and temperature and precipitation was investigated within and across
      cytotypes to test for associations between environmental factors and nuclear DNA
      content. KEY RESULTS: A euploid series (n = 6) of diploids to octoploids was
      documented through chromosome counts, and decaploids were suggested by flow
      cytometry. Increased variation in genome size among populations was found at
      higher ploidy levels, potentially associated with differential contributions of
      diploid parental genomes, variation in rates of genomic loss or gain, or
      undetected hybridization. Several accessions were detected with atypical genome
      sizes, including a diploid population of C. parviflora ssp. grandiflora with an
      18 % smaller genome than typical, and hexaploids of C. perfoliata and C.
      parviflora with genomes 30 % larger than typical. There was a slight but
      significant association of larger genome sizes with colder winter temperature
      across the C. perfoliata complex as a whole, and a strong association between
      lower winter temperatures and large genome size for tetraploid C. parviflora.
      CONCLUSIONS: The C. perfoliata complex is characterized by polyploids ranging
      from tetraploid to decaploid, with large magnitude variation in genome size at
      higher ploidy levels, associated in part with environmental variation in
      temperature.

PMID- 22962303
TI  - Expression and functional role of vacuolar H(+)-ATPase in human hepatocellular
      carcinoma.
AB  - Tumor cells often exist in a hypoxic microenvironment, which produces acidic
      metabolites. To survive in this harsh environment, tumor cells must exhibit a
      dynamic cytosolic pH regulatory system. Vacuolar H(+)-adenosine triphosphatase (V
      ATPase) is considered to play an important role in the regulation of the acidic
      microenvironment of some tumors. In this study, we made an investigation on the
      expression and functional role of V-ATPase in native human hepatocellular
      carcinoma (HCC). The results showed that the messenger RNA and protein expression
      levels of V-ATPase subunit ATP6L in native human HCC tissues were markedly
      increased, compared with normal liver tissues. Immunohistochemical analysis
      further confirmed the enhanced expression of V-ATPase ATP6L in human HCC cells
      and revealed that V-ATPase ATP6L was distributed in the cytoplasm and plasma
      membrane of HCC cells. The results from immunofluorescence and biotinylation of
      cell surface protein showed that V-ATPase ATP6L was conspicuously located in the
      plasma membrane of human HCC cells. Bafilomycin A1, a specific V-ATPase
      inhibitor, markedly slowed the intracellular pH (pHi) recovery after acid load in
      human HCC cells and retarded the growth of human HCC in orthotopic xenograft
      model. These results demonstrated that V-ATPase is up-regulated in human HCC and
      involved in the regulation of pHi of human HCC cells. The inhibition of V-ATPase
      can effectively retard the growth of HCC, indicating that V-ATPase may play an
      important role in the development and progression of human HCC, and targeting V
      ATPase may be a promising therapeutic strategy against human HCC.

PMID- 22962304
TI  - Maspin genetically and functionally associates with gastric cancer by regulating
      cell cycle progression.
AB  - Human SERPINB5, commonly known as maspin, has diverse functions as a tumor
      suppressor. In this study, we discovered that maspin has a novel role in cell
      cycle control, and common variants were discovered to be associated with gastric
      cancer. The genotypes of 836 unrelated Korean participants (including 430 with
      gastric cancer) were examined for 12 tag single-nucleotide polymorphisms (SNPs)
      and imputed for 178 SNPs in the maspin gene. Susceptibility to diffuse-type
      gastric cancer was strongly and significantly associated with several SNPs
      including rs3744941 (C>T) in the promoter (TT versus CC+CT, odds ratio = 0.56
      [0.37-0.83], P = 0.0038) and rs8089104 (C>T) in intron 1 (TT+CT versus CC, odds
      ratio = 1.7 [1.2-2.5], P = 0.0021). No SNPs were associated with susceptibility
      to intestinal-type gastric cancer. A haplotype of three highly correlated
      promoter SNPs associated with higher cancer risk showed 40% of the activity of a
      non-risk-associated haplotype promoter in the diffuse-type gastric cancer cell
      line MKN45. Maspin downregulation achieved either by a short hairpin RNA
      targeting maspin or overexpression of the E2F1-DP1 complex in MKN45 cells
      dramatically accelerated cell cycle progression and caused an increase of active
      CDC25C levels and a decrease of inactive CDK1 levels. In contrast, maspin
      upregulation had the opposite effect, substantially retarding cell proliferation.
      Therefore, our results suggest that a maspin promoter haplotype that reduces
      maspin gene expression accelerates cell cycle progression and, consequently, is
      associated with increased susceptibility to diffuse-type gastric cancer.
      Furthermore, a novel maspin-related pathway is demonstrated to underlie gastric
      carcinogenesis.

PMID- 22962305
TI  - Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer
      growth by targeting Aurora B.
AB  - Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has
      antimicrobial activity against both gram-positive and gram-negative organisms.
      Generally, ceftriaxone is used for a variety of infections such as community
      acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are
      the penicillin-binding proteins. However, other activities of ceftriaxone remain
      unknown. Herein, we report for the first time that ceftriaxone has antitumor
      activity in vitro and in vivo. Kinase profiling results predicted that Aurora B
      might be a potential 'off' target of ceftriaxone. Pull-down assay data confirmed
      that ceftriaxone could bind with Aurora B in vitro and in A549 cells.
      Furthermore, ceftriaxone (500 uM) suppressed anchorage-independent cell growth by
      targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in
      vivo xenograft animal model results showed that ceftriaxone effectively
      suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data
      suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers
      through its inhibition of Aurora B.

PMID- 22962307
TI  - Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis
      and enhances paclitaxel-induced cytotoxicity in breast cancer cells.
AB  - Cancer is caused by defects in the signalling mechanisms that govern cell
      proliferation and apoptosis. It is well known that calcium-dependent signalling
      pathways play a critical role in cell regulation. A tight control of calcium
      homeostasis by transporters and channel proteins is required to assure a proper
      functioning of the calcium-sensitive signal transduction pathways that regulate
      cell growth and apoptosis. The plasma membrane calcium ATPase 2 (PMCA2) has been
      recently identified as a negative regulator of apoptosis that can play a
      significant role in cancer progression by conferring cells resistance to
      apoptosis. We have previously reported an inhibitory interaction between PMCA2
      and the calcium-activated signalling molecule calcineurin in breast cancer cells.
      Here, we demonstrate that disruption of the PMCA2/calcineurin interaction in a
      variety of human breast cancer cells results in activation of the
      calcineurin/NFAT pathway, upregulation in the expression of the pro-apoptotic
      protein Fas Ligand and in a concomitant loss of cell viability. Reduction in cell
      viability is the consequence of an increase in cell apoptosis. Impairment of the
      PMCA2/calcineurin interaction enhances paclitaxel-mediated cytotoxicity of breast
      tumoral cells. Our results suggest that therapeutic modulation of the
      PMCA2/calcineurin interaction might have important clinical applications to
      improve current treatments for breast cancer patients.

PMID- 22962306
TI  - The Mullerian inhibiting substance type 2 receptor suppresses tumorigenesis in
      testes with sustained beta-catenin signaling.
AB  - Dysregulated WNT/beta-catenin signaling in murine testes results in a phenotype
      with complete germ cell loss that resembles human Sertoli cell-only syndrome. In
      other systems, including the ovary, dysregulated WNT/beta-catenin induces
      tumorigenesis but no tumors are observed in the mutant testes without deletion of
      a tumor suppressor, such as phosphatase and tensin homolog (PTEN). Mullerian
      inhibiting substance (MIS, also known as AMH), a member of the transforming
      growth factor-beta family of growth factors responsible for Mullerian duct
      regression in fetal males, has been shown to inhibit tumor growth in vitro and in
      vivo but its role as an endogenous tumor suppressor has never been reported. We
      have deleted the MIS type 2 receptor (MISR2), and thus MIS signaling, in mice
      with dysregulated WNT/beta-catenin and show that these mice develop testicular
      stromal tumors with 100% penetrance within a few months postnatal. The tumors are
      highly proliferative and have characteristics of either Sertoli cell tumors or
      progenitor Leydig cell tumors based on their marker profiles and histology.
      Phosphorylated Sma and mothers against decapentaplegic-related homolog 1/5/8 is
      absent in the tumors and beta-catenin target genes are induced. The tumor
      suppressor TP53 is also highly expressed in the tumors, as is phosphorylated
      gammaH2AX, which is indicative of DNA damage. The phenotype of these tumors
      closely resembles those observed when PTEN is also deleted in mice with
      dysregulated WNT/beta-catenin. Tumorigenesis in these mice provides conclusive
      evidence that physiological MIS signaling is a tumor suppressor mechanism and
      suggests that targeted treatment of MISR2-expressing cancers with therapeutic MIS
      should have a beneficial effect on tumor progression.

PMID- 22962308
TI  - Dabigatran-induced acute hepatitis.

PMID- 22962309
TI  - Correlation between red cell distribution width and coronary ectasia in the acute
      myocardial infarction.

PMID- 22962310
TI  - 17beta-Estradiol-induced interaction of ERalpha with NPPA regulates gene
      expression in cardiomyocytes.
AB  - AIMS: 17beta-Oestradiol (E2) and its receptors (ERalpha and ERbeta) are important
      regulators of physiological and pathological processes in the cardiovascular
      system. ER act in concert with other regulatory factors mediating oestrogenic
      effects. However, the underlying mechanisms modulating ER transcriptional
      activity are not fully elucidated. To gain better understanding of E2-induced
      ERalpha action in the human heart, we aimed to identify and functionally analyse
      interaction partners of ERalpha. METHODS AND RESULTS: Using yeast two-hybrid
      assays with a human heart cDNA library, we identified atrial natriuretic peptide
      precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERalpha
      interaction partner interacting in an E2-dependent manner. Mutation analyses and
      immunofluorescence data indicated that the LXXLL motif within NPPA is necessary
      for its E2-induced interaction with ERalpha, its action as a co-repressor of
      ERalpha, and its translocation into the nucleus of human and rat cardiomyocytes.
      Expression analysis and chromatin immunoprecipitation assays in a human left
      ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with
      E2/ERalpha, suppressing the transcriptional activity of ERalpha on E2-target
      genes, such as NPPA, connexin43, alphaactinin-2, nuclear factor of activated T
      cells, and collagens I and III. CONCLUSION: We characterize for the first time an
      E2-regulated interaction of NPPA with ERalpha in cardiomyocytes, that may be
      crucial in physiological and/or pathological cardiac processes, thereby
      representing a potential therapeutic target.

PMID- 22962311
TI  - Exercise-based cardiac rehabilitation improves endothelial function assessed by
      flow-mediated dilation but not by pulse amplitude tonometry.
AB  - We aimed to investigate the effect of exercise on endothelium-dependent
      vasodilator function assessed simultaneously in the brachial artery and in the
      distal arterial bed by flow-mediated dilation and the pulse amplitude tonometry
      method, respectively, in coronary artery disease patients. The study included 146
      patients with stable coronary artery disease (123 men, mean age 62 +/- 9 years)
      who participated in the Cardiac Rehabilitation and Genetics of Exercise
      performance study. All patients completed a 12-week supervised cardiac
      rehabilitation programme (three sessions per week at an intensity of 80% of the
      heart rate reserve). At baseline and upon completion of the training, we measured
      brachial artery diameters by means of ultrasound scanning (linear array
      transducer of 12 MHz) and simultaneously assessed pulse amplitudes in the
      fingertip using a pulse amplitude tonometry device both at rest and after
      reactive hyperaemia induced by a 5-min forearm cuff occlusion. Peak oxygen uptake
      significantly increased (+22%; p < 0.0001) and flow-mediated dilation improved
      from 10.0% to 13.1% (+37%; p < 0.0001), whereas the reactive hyperaemia index of
      the pulse amplitude tonometry method remained unchanged (p = 0.47) following
      exercise-based cardiac rehabilitation. However, the basal digital pulse amplitude
      (+58%; p < 0.001) increased as a result of training, as did the digital pulse
      amplitude after reactive hyperaemia (+22%; p < 0.05). Exercise-based cardiac
      rehabilitation is associated with an improvement in endothelial function, as can
      be measured by flow-mediated dilation but not by the reactive hyperaemia index of
      the pulse amplitude tonometry method. 

PMID- 22962312
TI  - DECIPHER: web-based, community resource for clinical interpretation of rare
      variants in developmental disorders.
AB  - Patients with developmental disorders often harbour sub-microscopic deletions or
      duplications that lead to a disruption of normal gene expression or perturbation
      in the copy number of dosage-sensitive genes. Clinical interpretation for such
      patients in isolation is hindered by the rarity and novelty of such disorders.
      The DECIPHER project (https://decipher.sanger.ac.uk) was established in 2004 as
      an accessible online repository of genomic and associated phenotypic data with
      the primary goal of aiding the clinical interpretation of rare copy-number
      variants (CNVs). DECIPHER integrates information from a variety of bioinformatics
      resources and uses visualization tools to identify potential disease genes within
      a CNV. A two-tier access system permits clinicians and clinical scientists to
      maintain confidential linked anonymous records of phenotypes and CNVs for their
      patients that, with informed consent, can subsequently be shared with the wider
      clinical genetics and research communities. Advances in next-generation
      sequencing technologies are making it practical and affordable to sequence the
      whole exome/genome of patients who display features suggestive of a genetic
      disorder. This approach enables the identification of smaller intragenic
      mutations including single-nucleotide variants that are not accessible even with
      high-resolution genomic array analysis. This article briefly summarizes the
      current status and achievements of the DECIPHER project and looks ahead to the
      opportunities and challenges of jointly analysing structural and sequence
      variation in the human genome.

PMID- 22962314
TI  - Revisiting the classification of clinical phenotypes of anti-neutrophil
      cytoplasmic antibody-associated vasculitis: a cluster analysis.
AB  - BACKGROUND: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic
      polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV) defined historically by clinical and histological
      features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To
      identify novel subgroupings, cluster analysis was used to explore the phenotypic
      spectrum of AAV. METHODS: This study used a dataset of patients newly diagnosed
      as having GPA and MPA enrolled in five clinical trials. One cluster model
      included nine clinical baseline variables as input variables, and a second
      cluster model additionally included ANCA specificities. The clustering process
      involved multiple correspondence analyses followed by hierarchical ascendant
      cluster analysis. The clinical relevance of the generated clusters was analysed
      by their summary characteristics and outcomes. RESULTS: The analyses involved
      data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster
      models resulted in five partially redundant clusters of subjects, and the model
      including ANCA resulted in more pertinent separations. These clusters were named
      'renal AAV with proteinase 3 (PR3)-ANCA' (40% of subjects), 'renal AAV without
      PR3-ANCA' (32%) and 'non-renal AAV' (12%), 'cardiovascular AAV' (9%) and
      'gastrointestinal AAV' (7%). The five clusters had distinct death and relapse
      rates. On the basis of 4 variables, 651 subjects (97%) could be accurately
      allocated to 1 of the 5 classes. CONCLUSIONS: This analysis suggests that AAV
      encompasses five classes associated with different outcomes. As compared with the
      traditional GPA-MPA separation, this classification system may better reflect the
      phenotypic spectrum of AAV.

PMID- 22962315
TI  - Whole microvascular unit deletions in dermatomyositis.
AB  - OBJECTIVES: The pathophysiology of dermatomyositis (DM) remains unclear,
      combining immunopathological mechanisms with ischaemic changes regarded as a
      consequence of membranolytic attack complex (MAC)-induced capillary destruction.
      The study is a reappraisal of the microvascular involvement in light of the
      microvascular organisation in normal human muscle. METHODS: Muscle
      microvasculature organisation was analysed using 3D reconstructions of serial
      sections immunostained for CD31, and histoenzymatic detection of endogenous
      alkaline phosphatase activity of microvessels. An unbiased point pattern analysis
      based method was used to evaluate focal capillary loss. Double immunostainings
      identified cell types showing MAC deposits. RESULTS: The normal arterial tree
      includes perimysial arcade arteries, transverse arteries penetrating
      perpendicularly into the endomysium and terminal arterioles feeding a
      microvascular unit (MVU) of six to eight capillaries contacting an average of
      five myofibres. Amyopathic DM cases (n=3) and non-necrotic fascicles of early DM
      cases (n=27), showed patchy capillary loss in the form of 6-by-6 capillary drop
      out, corresponding to depletion of one or multiple MVUs. MAC deposits were also
      clustered (5-8 immunostained structures, including endothelial cells, but also
      pericytes, mesenchymal cells and myosatellite cells). CONCLUSIONS: Capillary loss
      may not be the primary cause of muscle ischaemia in DM. The primary event rather
      stands upstream, probably at the level of perimysial arcade arteries around which
      inflammatory infiltrates predominate and which lumen may show narrowing in
      chronic DM. Ischaemia-reperfusion injury, which is favoured by autoimmune
      backgrounds in experimental models and which activates the complement cascade in
      capillaries, could represent an hitherto unsuspected (and potentially
      preventable) mechanism of muscle damage in DM.

PMID- 22962316
TI  - Are digestive symptoms in women presenting with pelvic endometriosis specific to
      lesion localizations? A preliminary prospective study.
AB  - STUDY QUESTION: What are the types and frequency of digestive symptoms in
      patients with different localizations of pelvic endometriosis and which specific
      symptoms are related to rectal stenosis? SUMMARY ANSWER: There is a high
      prevalence of digestive complaints in women presenting with superficial pelvic
      endometriosis and deep endometriosis sparing the rectum. WHAT IS KNOWN ALREADY:
      Women presenting with pelvic endometriosis frequently report gastrointestinal
      complaints of increased intensity during menstruation, which are not necessarily
      linked to the infiltration of the disease into the rectal wall. Even though
      intrarectal protrusion of the nodule can have an impact on bowel movement, only a
      minority of women with rectal nodules seemed to be concerned by significant
      narrowing of the rectum. STUDY DESIGN AND SIZE: This three-arm cohort prospective
      study included 116 women and was carried out over 22 consecutive months.
      PARTICIPANTS, SETTING AND METHODS: Prospective recording of data was performed
      for women treated for Stage 1 endometriosis involving the Douglas pouch (n = 21),
      deep endometriosis without digestive infiltration (n = 42) and deep endometriosis
      infiltrating the rectum (n = 53). Patient characteristics, pelvic pain and data
      from preoperative standardized questionnaires The Gastrointestinal Quality of
      Life Index (GIQLI), the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS) and
      the MOS 36-Item Short-Form Health Survey (SF-36) were compared according to
      endometriosis localization. MAIN RESULTS: The values of total KESS and total
      GIQLI score were comparable for the three groups, as were a majority of the
      digestive complaints. Women presenting with rectal endometriosis were more likely
      to report an increase in intensity and length of dysmenorrhoea, while deep
      dyspareunia appeared to be more severe in women with superficial endometriosis.
      Women presenting with rectal endometriosis were more likely to present cyclic
      defecation pain (67.9%), cyclic constipation (54.7%) and a significantly longer
      stool evacuation time, although these complaints were also frequent in the other
      two groups (38.1 and 33.3% in women with Stage 1 endometriosis and 42.9 and 26.2%
      in women with deep endometriosis without digestive involvement, respectively). No
      independent clinical factor was found to be related to infiltration of the rectum
      by deep endometriosis. Among women with rectal endometriosis, only 26.4%
      presented with rectal stenosis. These women were significantly more likely to
      report constipation, defecation pain, appetite disorders, longer evacuation time
      and increased stool consistency without laxatives. LIMITATIONS: Patients treated
      for pelvic endometriosis in a tertiary referral centre may not be representative
      of the general endometriosis population presenting with those lesions.
      Statistically significant differences were revealed between the three groups;
      however, the results were based on a small number of subjects, which carries an
      inherent risk of type II error particularly when comparing variables with closed
      values. WIDER IMPLICATIONS OF THE FINDINGS: In women presenting with pelvic
      endometriosis, it seems likely that various digestive symptoms are the
      consequence of cyclic inflammatory phenomena leading to irritation of the
      digestive tract, rather than to actual infiltration of the disease itself into
      the rectum, with the exception of a limited number of cases where the disease
      leads to rectal stenosis. STUDY FUNDING/COMPETING INTEREST: The North-West Inter
      Regional Female Cohort for Patients with Endometriosis (CIRENDO) is financed by
      the G4 Group (The University Hospitals of Rouen, Lille, Amiens and Caen). No
      financial support was specifically received for this study. The authors declare
      no conflict of interest.

PMID- 22962318
TI  - Epilepsies in infancy.
AB  - To evaluate and manage epileptic seizures and other paroxysmal events in infants,
      it is necessary to ask five key questions: (1) Is this a type of epilepsy?; (2)
      What seizure type(s) are occurring?; (3) Do these seizure types, combined with
      factors such as age at onset and EEG features, constitute an 'epilepsy
      syndrome'?; (4) What investigations do we need to do in searching for an
      underlying aetiology? and finally, (5) What is the prognosis for neurological and
      developmental state in later life? This review considers epilepsies that have an
      onset in infancy but after the perinatal period, outlines the commoner epilepsy
      syndromes occurring in this age group and describes paroxysmal events that can
      mimic epilepsy. Epilepsies in infancy may be the manifestation of a genetic
      predisposition associated with a benign course and good prognosis for
      neurodevelopment. In contrast, they may pose the challenging situation of
      'epileptic encephalopathy', rare but potentially treatable metabolic conditions,
      or structural abnormalities with poor developmental outlook and intractable
      seizures. Seizures in infancy are relatively rare and there is a wide range of
      underlying causes, some of which require specific treatments to avoid preventable
      neurodevelopmental damage. Guidance from the National Institute for Health and
      Clinical Excellence suggests early referral of cases of infantile epilepsy to a
      tertiary centre.

PMID- 22962319
TI  - Brain drain in sub-Saharan Africa: contributing factors, potential remedies and
      the role of academic medical centres.
AB  - A double jeopardy exists in resource-limited settings (RLS) in sub-Saharan Africa
      (SSA): there are a disproportionately greater number of acutely ill patients, but
      a paucity of healthcare workers (HCW) to care for them. SSA has 25% of the global
      disease burden but only 3% of the world's HCW. Thirty-two SSA countries do not
      meet the WHO minimum of 23 HCW per 10000 population. Contributing factors include
      insufficient supply, inadequate distribution and migration. Potential remedies
      include international workforce policies, non-governmental organisations,
      national and international medical organisations' codes of conduct, inter-country
      collaborations, donor-directed policies and funding to train more people in
      country, and health system strengthening and task-shifting. Collaborations among
      academic institutions from resource-rich and poor countries can help address HCW
      supply, distribution and migration. It is now opportune to harness bright,
      committed people from academic centres in resource-rich and poor settings to
      create long-term, collaborative relationships focused on training, clinical
      skills and locally relevant research endeavours, who mutually strive for HCW
      retention, less migration, and ultimately sufficient HCW to provide optimal care
      in all RLS.

PMID- 22962313
TI  - Integration of genome-wide association studies with biological knowledge
      identifies six novel genes related to kidney function.
AB  - In conducting genome-wide association studies (GWAS), analytical approaches
      leveraging biological information may further understanding of the
      pathophysiology of clinical traits. To discover novel associations with estimated
      glomerular filtration rate (eGFR), a measure of kidney function, we developed a
      strategy for integrating prior biological knowledge into the existing GWAS data
      for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide
      polymorphism (SNPs) in genes that are connected by functional evidence,
      determined by literature mining and gene ontology (GO) hierarchies, to genes near
      previously validated eGFR associations. It then requires association thresholds
      consistent with multiple testing, and finally evaluates novel candidates by
      independent replication. Among the samples of European ancestry, we identified a
      genome-wide significant SNP in FBXL20 (P = 5.6 * 10(-9)) in meta-analysis of all
      available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and
      SLC7A6 genes meeting multiple-testing corrected significance for replication and
      overall P-values of 4.5 * 10(-4)-2.2 * 10(-7). Neither the novel PLEKHA1 nor
      FBXL20 associations, both further supported by association with eGFR among
      African Americans and with transcript abundance, would have been implicated by
      eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was
      identified through connection with the previously known eGFR gene DAB2 and
      extends understanding of the megalin system in kidney function. These findings
      highlight integration of existing genome-wide association data with independent
      biological knowledge to uncover novel candidate eGFR associations, including
      candidates lacking known connections to kidney-specific pathways. The strategy
      may also be applicable to other clinical phenotypes, although more testing will
      be needed to assess its potential for discovery in general.

PMID- 22962320
TI  - What size of vegetation is an indication for surgery in endocarditis?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether the of vegetations in endocarditis
      is an indication for surgery. Altogether, 102 papers were found using the
      reported search; 16 papers were identified that provided the best evidence to
      answer the question. The authors, journal, date, country of publication, patient
      group, study type, relevant outcomes and results were tabulated. The vegetation
      size was classified into small (<5 mm), medium (5-9 mm), or large (>=10 mm) using
      echocardiography and a vegetation size of >=10 mm was a predictor of embolic
      events and increased mortality in most of the studies with left-sided infective
      endocarditis. For large vegetations--that commonly resulted from the failure of
      antibiotics to decrease the vegetation size during 4-8 weeks' therapy--and
      complications such as perivalvular abscess formation, valvular destruction and
      persistent pyrexia necessitated surgical intervention. In a multicentre
      prospective cohort study of 384 consecutive patients with infective endocarditis,
      it was observed that a vegetation size of >10 mm and severe vegetation mobility
      were predictors of new embolic events. Equally, a meta-analysis showed that the
      echocardiographic detection of a vegetation size of >=10 mm in patients with left
      sided infective endocarditis posed significantly increased risk of embolic
      events. In another prospective cohort study of 211 patients, it was observed that
      there was an increased risk of embolization with vegetations of >=10 mm. In
      similarly another study of 178 consecutive patients with infective endodarditis
      assessed by echocardiographic study, it was found out that there was a
      significantly higher incidence of embolism with a vegetation size >10 mm (60%,
      P<0.001). When using the area of the vegetation, a vegetation size of >1.8 cm(2)
      predicted the development of a complication. Assuming that the vegetation was a
      sphere, the calculated diameter will be 8 mm when using 4Omegar(2) for the area.
      However, for right-sided infection endocarditis, a vegetation size of >20 mm was
      associated with a higher mortality when compared with a vegetation size of <=20
      mm. There is strong evidence to suggest that a vegetation size of >=10 mm
      especially for left-sided infective endocarditis is an indication for surgery.

PMID- 22962321
TI  - Artificial chordae for degenerative mitral valve disease: critical analysis of
      current techniques.
AB  - The surgical repair of degenerative mitral valve disease involves a number of
      technical points of importance. The use of artificial chordae for the repair of
      degenerative disease has increased as a part of the move from mitral valve
      replacement to repair of the mitral valve. The use of artificial chordae provides
      an alternative to the techniques pioneered by Carpentier (including the
      quadrangular resection, transfer of native chordae and papillary muscle
      shortening/plasty), which can be more technically difficult. Despite a growth in
      their uptake and the indications for their use, a number of challenges remain for
      the use of artificial chordae in mitral valve repair, particularly in the
      determination of the correct length to ensure optimal leaflet coaptation. Here,
      we analyse over 40 techniques described for artificial chordae mitral valve
      repair in the setting of degenerative disease.

PMID- 22962322
TI  - The impact of intraoperative vasopressin infusion in complex neonatal cardiac
      surgery.
AB  - OBJECTIVES: Although recent advances have led to a better understanding of the
      beneficial effects of vasopressin on haemodynamics in paediatric cardiac surgery,
      not much information is available on the adverse effects. The objective of this
      study was to assess the impact of intraoperative vasopressin infusion on
      postoperative liver, renal and haemostatic function and lactate levels in
      neonates undergoing cardiac surgery. METHODS: We reviewed data from 34
      consecutive neonates who had undergone complex cardiac surgery. The cohort was
      divided into two groups according to the use of vasopressin. Seventeen patients
      received vasopressin [vasopressin (+) group], and 17 patients did not
      [vasopressin (-) group]. RESULTS: No differences between the groups in terms of
      age, weight, cardiopulmonary bypass time, Risk Adjustment for Congenital Heart
      Surgery-1 score or the comprehensive Aristotle score were seen. No differences in
      the systolic or diastolic arterial blood pressures, heart rate or inotropic score
      upon admission to the intensive care unit were observed between the groups. No
      adverse effects on the aminotransferase levels were seen. The vasopressin (+)
      group had higher urea and creatinine levels. All the patients except one received
      peritoneal dialysis on the day of surgery. Thirteen patients in the vasopressin
      (+) group and 7 patients in the vasopressin (-) group continued to require
      peritoneal dialysis on postoperative day 5 (POD 5) (P = 0.04). The platelet count
      had decreased to a significantly lower level in the vasopressin (+) group on POD
      5 [97 x 10(3)/mm(3) (range: 40-132 x 10(3)/mm(3))]. A tendency toward a high
      lactate concentration was seen in the vasopressin (+) group. In comparison with
      the vasopressin (-) group, the number of patients whose lactate level remained
      above 2.0 mmol/l was higher in the vasopressin (+) group on PODs 2 and 3 (17
      patients vs 8 patients, P < 0.01 and 15 patients vs 7 patients, P = 0.01,
      respectively). CONCLUSIONS: These findings suggest that the intraoperative use of
      vasopressin extends the period of peritoneal dialysis, reduces platelet counts
      and delays the recovery of the lactate concentration. Intraoperative vasopressin
      infusion should not be used routinely, but only in catecholamine-refractory
      shock.

PMID- 22962323
TI  - Is it safe to cut pacing wires flush with the skin instead of removing them?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether it is safe to cut the temporary
      epicardial pacing wires (TEPWs) flush with the patient's skin surface prior to
      discharge. Altogether 105 relevant papers were identified of which 13 case
      reports represented the best evidence to answer the question. The author,
      journal, date, country of publication, complications, the culprit TEPW and
      relevant outcomes are tabulated. All case reports demonstrated a wide spectrum of
      complications. Complications from a retained TEPW mainly arise after a long
      dormant period. A recent case report has demonstrated the herniation of intra
      abdominal contents through a diaphragmatic defect created by the abandoned
      epicardial pacing wires after a few decades. In multiple case reports, the
      migration of TEPW was the culprit of serious complications. In two case reports,
      the TEPWs attached to the right chambers of the heart had migrated to the
      pulmonary artery via the right atrium and then the right ventricle. In one case
      report, a similar migration of the right ventricular TEPW to the right
      ventricular outflow track was observed. The TEPW migration was not limited to the
      right side of the heart, as in one case report the right atrial TEPW had migrated
      to the right carotid artery via the ascending aorta. A distant extravascular
      migration of TEPWs to the skin surface and intraperitoneal and pelvic cavities
      has also been reported. Retained TEPWs have also been reported to inflict
      complications locally. One case report has shown a large right-sided para-cardiac
      mass caused by a right atrial TEPW. In two other case reports, the
      bronchocutaneous fistula, lobar consolidation and bronchiectasis were the
      manifestations of a retained TEPW. We conclude that the retention of TEPW after
      cardiac surgery is not necessarily safe and may cause severe complications. We
      recommend that TEPWs should be completely removed when possible. If TEPWs are
      retained, this should be appropriately documented and the surgeon should be
      mindful of this when the patient presents with complications postoperatively.

PMID- 22962324
TI  - Synthetic lethal screening with small-molecule inhibitors provides a pathway to
      rational combination therapies for melanoma.
AB  - Recent data show that extracellular signals are transmitted through a network of
      proteins rather than hierarchical signaling pathways, suggesting that the
      inhibition of a single component of a canonical pathway is insufficient for the
      treatment of cancer. The biologic outcome of signaling through a network is
      inherently more robust and resistant to inhibition of a single network component.
      In this study, we conducted a functional chemical genetic screen to identify
      novel interactions between signaling inhibitors that would not be predicted on
      the basis of our current understanding of signaling networks. We screened over
      300 drug combinations in nine melanoma cell lines and have identified pairs of
      compounds that show synergistic cytotoxicity. The synergistic cytotoxicities
      identified did not correlate with the known RAS and BRAF mutational status of the
      melanoma cell lines. Among the most robust results was synergy between sorafenib,
      a multikinase inhibitor with activity against RAF, and diclofenac, a nonsteroidal
      anti-inflammatory drug (NSAID). Drug substitution experiments using the NSAIDs
      celecoxib and ibuprofen or the MAP-ERK kinase inhibitor PD325901 and the RAF
      inhibitor RAF265 suggest that inhibition of COX and mitogen-activated protein
      kinase signaling are targets for the synergistic cytotoxicity of sorafenib and
      diclofenac. Cotreatment with sorafenib and diclofenac interrupts a positive
      feedback signaling loop involving extracellular signal-regulated kinase, cellular
      phospholipase A2, and COX. Genome-wide expression profiling shows synergy
      specific downregulation of survival-related genes. This study has uncovered novel
      functional drug combinations and suggests that the underlying signaling networks
      that control responses to targeted agents can vary substantially, depending on
      unexplored components of the cell genotype.

PMID- 22962325
TI  - Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant
      melanoma: a case illustrating the challenges for personalized medicine.
AB  - Targeted therapies are increasingly being used to treat a variety of cancers.
      Their efficacy depends upon the accurate detection and targeting of a specific
      mutation or aberration in the tumor. All cancers, such as melanoma, are
      molecularly heterogeneous, with drug-resistant subclones present before the
      treatment or emerging as a result of targeted therapies. Here, we show
      intralesional molecular heterogeneity in a progressing V600E BRAF-mutant melanoma
      metastasis from a patient treated for 7 months with the BRAF inhibitor
      vemurafenib. In the single metastasis, two distinct subclones were observed, both
      V600E BRAF-mutant and only one with an additional G13R NRAS mutation. Molecular
      heterogeneity even at the intralesional level shows that personalizing or
      adjusting therapies based on genotyping of a portion of a single lesion may not
      accurately depict the molecular profile or drivers of oncogenesis across the
      entire patient's melanoma.

PMID- 22962326
TI  - Ceramide--antiestrogen nanoliposomal combinations--novel impact of hormonal
      therapy in hormone-insensitive breast cancer.
AB  - Although the sphingolipid ceramide exhibits potent tumor suppressor effects,
      efforts to harness this have been hampered by poor solubility, uptake,
      bioavailability, and metabolic conversion. Therefore, identification of avenues
      to improve efficacy is necessary for development of ceramide-based therapies. In
      this study, we used mutant p53, triple-negative breast cancer (TNBC) cells, a
      type of breast cancer highly refractory to treatment, and cell-permeable
      nanoliposomal C6-ceramide in conjunction with the antiestrogen tamoxifen, which
      has been shown to be an effective modulator of ceramide metabolism. We show for
      the first time that nanoliposomal tamoxifen enhances nanoliposomal C6-ceramide
      cytotoxicity in cultured TNBC cells, a response that was accompanied by induction
      of cell-cycle arrest at G(1) and G(2), caspase-dependent induction of DNA
      fragmentation, and enhanced mitochondrial and lysosomal membrane permeability at
      18 and 2 hours, respectively. Tamoxifen metabolites were also effective. Only
      tamoxifen promoted lysosomal membrane permeability. In addition, we show for the
      first time that tamoxifen inhibits acid ceramidase, as measured in intact cell
      assays; this effect was irreversible. Together, our findings show that tamoxifen
      magnifies the antiproliferative effects of C6-ceramide via combined targeting of
      cell-cycle traverse and lysosomal and mitochondrial integrity. We adduce that C6
      ceramide-induced apoptosis is amplified by tamoxifen's impact on lysosomes and
      perhaps accompanying inhibition of acid ceramidase, which could result in
      decreased levels of sphingosine 1-phosphate. This drug regimen could serve as a
      promising therapy for chemoresistant and triple-negative types of breast cancer,
      and thus represents an indication for tamoxifen, irrespective of estrogen
      receptor status.

PMID- 22962327
TI  - Acceleration of collateral development by carcinoembryonic antigen-related cell
      adhesion molecule 1 expression on CD11b/+Gr-1+ myeloid cells--brief report.
AB  - OBJECTIVE: Previously, we demonstrated the relevance for endothelial
      carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression in
      collateral formation. However, a proarteriogenic role for CEACAM1(+) myeloid
      cells is unknown. Here, we investigated the contribution of CEACAM1(+) myeloid
      cells on collateral formation. METHODS AND RESULTS: Collateral growth and
      vascular remodeling were analyzed in CEACAM1-competent and CEACAM1 null mice
      after femoral artery ligation in hindlimb ischemia. Reperfusion of the adductor
      muscles was evaluated by Laser Doppler measurements and microcomputed tomography
      imaging. In CEACAM1 null mice, poor reperfusion and reduced collateral formation
      were observed, accompanied by reduction in arterial diameters. Using flow
      cytometry, we identified an increase of the muscle-resident CD11b(+)/granulocyte
      receptor-1+ (Gr-1+) population in CEACAM1 null mice only, pointing toward a
      CEACAM1-dependent functional deviation. Direct and reciprocal bone marrow
      transplantations between CEACAM1-competent and CEACAM1 null mice, and antibody
      mediated depletion of the CD11b(+)/Gr-1(+) population, confirmed the requirement
      of CEACAM1 expression on the CD11b(+)/Gr-1(+) population for reestablishment of
      perfusion after arterial occlusion. CONCLUSIONS: CEACAM1 expression on
      CD11b(+)/Gr-1(+) myeloid cells is a prerequisite for adequate collateral
      formation.

PMID- 22962328
TI  - Macrophages regulate smooth muscle differentiation of mesenchymal stem cells via
      a prostaglandin F2alpha-mediated paracrine mechanism.
AB  - OBJECTIVE: Mesenchymal stem cells are useful for vascular regeneration of injured
      tissues. Macrophages are involved in acute or chronic inflammatory diseases, and
      interleukin-1beta (IL-1beta), a proinflammatory cytokine, plays a key role in the
      activation of macrophages within injured tissues. To explore the role of
      macrophages on mesenchymal stem cell-mediated vascular regeneration, we examined
      the effects of IL-1beta-activated macrophages on differentiation of human adipose
      tissue-derived mesenchymal stem cells (hASCs) to smooth muscle cells (SMCs) and
      the vascular regenerative capacity of the differentiated SMCs in a hindlimb
      ischemia animal model. METHODS AND RESULTS: We demonstrate that IL-1beta
      conditioned medium from RAW 264.7 macrophages induces differentiation of human
      adipose tissue-derived mesenchymal stem cells to alpha-smooth muscle actin
      positive SMCs, and the differentiated SMCs exhibited increased contractility in
      response to KCl and carbachol treatment. Transplantation of the differentiated
      SMCs attenuated severe hindlimb ischemia and promoted vascular regeneration. IL
      1beta treatment stimulated secretion of prostaglandin F(2alpha) from RAW 264.7
      cells. Small interfering RNA-mediated silencing of the prostaglandin F(2alpha)
      receptor completely abrogated IL-1beta conditioned medium-stimulated alpha-smooth
      muscle actin expression. Moreover, prostaglandin F(2alpha) treatment stimulated
      expression of alpha-smooth muscle actin in human adipose tissue-derived
      mesenchymal stem cells. CONCLUSIONS: These results suggest that IL-1beta
      activated macrophages promote differentiation of human adipose tissue-derived
      mesenchymal stem cells to SMCs through a prostaglandin F(2alpha)-mediated
      paracrine mechanism.

PMID- 22962330
TI  - Biological function through network topology: a survey of the human diseasome.
AB  - Molecular network data are increasingly becoming available, necessitating the
      development of well performing computational tools for their analyses. Such tools
      enabled conceptually different approaches for exploring human diseases to be
      undertaken, in particular, those that study the relationship between a multitude
      of biomolecules within a cell. Hence, a new field of network biology has emerged
      as part of systems biology, aiming to untangle the complexity of cellular network
      organization. We survey current network analysis methods that aim to give insight
      into human disease.

PMID- 22962329
TI  - Endocardial cushion morphogenesis and coronary vessel development require chicken
      ovalbumin upstream promoter-transcription factor II.
AB  - OBJECTIVE: Septal defects and coronary vessel anomalies are common congenital
      heart defects, yet their ontogeny and the underlying genetic mechanisms are not
      well understood. Here, we investigated the role of chicken ovalbumin upstream
      promoter-transcription factor II (COUP-TFII, NR2F2) in cardiac organogenesis.
      METHODS AND RESULTS: We analyzed embryos deficient in COUP-TFII and observed a
      spectrum of cardiac defects, including atrioventricular septal defect, thin
      walled myocardium, and abnormal coronary morphogenesis. We show by expression
      analysis that COUP-TFII is expressed in the endocardium and the epicardium but
      not in the myocardium of the ventricle. Using endothelial-specific COUP-TFII
      mutants and molecular approaches, we show that COUP-TFII deficiency resulted in
      endocardial cushion hypoplasia. This was attributed to the reduced growth and
      survival of atrioventricular cushion mesenchymal cells and defective epithelial
      mesenchymal transformation (EMT) in the underlying endocardium. In addition, the
      endocardial EMT defect was accompanied by downregulation of Snai1, one of the
      master regulators of EMT, and upregulation of vascular endothelial-cadherin.
      Furthermore, we show that although COUP-TFII does not play a major role in the
      formation of epicardial cell cysts, it is critically important for the formation
      of epicardium. Ablation of COUP-TFII impairs epicardial EMT and coronary plexus
      formation. CONCLUSIONS: Our results reveal that COUP-TFII plays cell-autonomous
      roles in the endocardium and the epicardium for endocardial and epicardial EMT,
      which are required for proper valve and coronary vessel formation during heart
      development.

PMID- 22962331
TI  - Identification and characterization of distinct C-terminal domains of the human
      hydroxycarboxylic acid receptor-2 that are essential for receptor export,
      constitutive activity, desensitization, and internalization.
AB  - The human hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A and
      HM74a, was first identified as a niacin receptor and has recently received
      significant attention because of its potential to clinically modify plasma lipids
      in a favorable manner. Our recent studies have demonstrated that the niacin
      induced internalization of HCA2 receptors is regulated by G protein-coupled
      receptor kinase (GRK) 2 and arrestin3 and that internalized receptors rapidly
      recycle back to the cell surface. The investigation presented here used a
      combination of amino acid deletion and site-directed mutagenesis to identify
      structural and functional domains within the HCA2 C terminus and explore their
      potential roles in receptor phosphorylation, desensitization, and
      internalization. We first constructed four mutants with deletions of 10 to 15
      amino acids each that were distinct from truncated mutants. We successfully
      identified different domains responsible for receptor export, constitutive
      activity, desensitization, phosphorylation, and internalization. We also
      generated a comprehensive series of alanine substitution mutants, replacing
      conserved serine and threonine residues in the C terminus with alanine residues
      to pinpoint the key residues that are essential for GRK2-mediated phosphorylation
      and arrestin3 association. Moreover, we found that a sequence from residues 329
      to 343 in the C-terminal tail of HCA2 plays a crucial role in keeping HCA2 in an
      inactive conformation. These data demonstrate the importance of distinct domains
      within the C terminus of HCA2 for receptor cell surface expression,
      desensitization, and internalization and phosphorylation and stabilization of an
      inactive receptor conformation.

PMID- 22962333
TI  - Winogradskyella litorisediminis sp. nov., isolated from coastal sediment.
AB  - A Gram-staining-negative, non-flagellated, non-gliding, aerobic, rod-shaped
      bacterium, designated DPS-8(T), was isolated from coastal sediment of Geoje
      island in the South Sea, South Korea, and subjected to a polyphasic study. Strain
      DPS-8(T) grew optimally at 30  degrees C, at pH 7.0-7.5 and in the presence of 2
      % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene
      sequences showed that strain DPS-8(T) joined the clade comprising the type
      strains of Winogradskyella species with a high bootstrap resampling value of 93.5
      %. Phylogenetic trees constructed using maximum-likelihood and maximum-parsimony
      algorithms revealed that strain DPS-8(T) belonged to the genus Winogradskyella.
      Strain DPS-8(T) exhibited 94.1-96.5 % 16S rRNA gene sequence similarity to the
      type strains of species of the genus Winogradskyella. Strain DPS-8(T) contained
      MK-6 as the predominant menaquinone and iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 0 3
      OH and C16 : 1omega7c and/or iso-C15 : 0 2-OH as the major fatty acids. The major
      polar lipids of strain DPS-8(T) were phosphatidylethanolamine and two
      unidentified lipids. The DNA G+C content of strain DPS-8(T) was 34.7 mol%.
      Differential phenotypic properties, together with its phylogenetic
      distinctiveness, revealed that strain DPS-8(T) is separate from recognized
      species of the genus Winogradskyella. On the basis of the data presented, strain
      DPS-8(T) is considered to represent a novel species of the genus Winogradskyella,
      for which the name Winogradskyella litorisediminis sp. nov. is proposed. The type
      strain is DPS-8(T) ( = KCTC 32110(T) = CCUG 62215(T)).

PMID- 22962334
TI  - Dyadobacter jejuensis sp. nov., isolated from seawater.
AB  - A taxonomic study was carried out on a novel bacterial strain, designated
      AM1R11(T), which was isolated from seawater of Jeju Island in Korea. Cells of the
      isolate were found to be Gram-negative, rod-shaped and non-motile. Comparison of
      the 16S rRNA gene sequences indicated that the isolate belonged to the family
      Cytophagaceae, with Dyadobacter ginsengisoli Gsoil 043(T) as its closest
      relative, with a similarity of 96.6 %. It contained summed feature 3 (comprising
      C16 : 1omega7c and/or C16 : 1omega6c, 36.9 %), iso-C15 : 0 (16.5 %) and C16 :
      1omega5c (16.3 %) as the major fatty acids and MK-7 as the predominant
      menaquinone. The polar lipid profile of strain AM1R11(T) revealed the presence of
      phosphatidylethanolamine, one aminolipid and four unidentified lipids (L1, L2, L3
      and L4). The DNA G+C content of strain AM1R11(T) was 45.1 mol%. On the basis of
      the evidence presented, it is concluded that strain AM1R11(T) represents a novel
      species of the genus Dyadobacter, for which the name Dyadobacter jejuensis sp.
      nov. is proposed. The type strain is AM1R11(T) ( = KACC 16446(T) = JCM 17918(T)).

PMID- 22962332
TI  - Gbetagamma inhibits exocytosis via interaction with critical residues on soluble
      N-ethylmaleimide-sensitive factor attachment protein-25.
AB  - Spatial and temporal regulation of neurotransmitter release is a complex process
      accomplished by the exocytotic machinery working in tandem with numerous
      regulatory proteins. G-protein betagamma dimers regulate the core process of
      exocytosis by interacting with the soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) proteins soluble N-ethylmaleimide-sensitive
      factor attachment protein-25 (SNAP-25), syntaxin 1A, and synaptobrevin.
      Gbetagamma binding to ternary SNAREs overlaps with calcium-dependent binding of
      synaptotagmin, inhibiting synaptotagmin-1 binding and fusion of the synaptic
      vesicle. To further explore the binding sites of Gbetagamma on SNAP-25, peptides
      based on the sequence of SNAP-25 were screened for Gbetagamma binding. Peptides
      that bound Gbetagamma were subjected to alanine scanning mutagenesis to determine
      their relevance to the Gbetagamma-SNAP-25 interaction. Peptides from this screen
      were tested in protein-protein interaction assays for their ability to modulate
      the interaction of Gbetagamma with SNAP-25. A peptide from the C terminus,
      residues 193 to 206, significantly inhibited the interaction. In addition, Ala
      mutants of SNAP-25 residues from the C terminus of SNAP-25, as well as from the
      amino-terminal region decreased binding to Gbeta1gamma1. When SNAP-25 with eight
      residues mutated to alanine was assembled with syntaxin 1A, there was
      significantly reduced affinity of this mutated t-SNARE for Gbetagamma, but it
      still interacted with synaptotagmin-1 in a Ca2+ -dependent manner and
      reconstituted evoked exocytosis in botulinum neurotoxin E-treated neurons.
      However, the mutant SNAP-25 could no longer support 5-hydroxytryptamine-mediated
      inhibition of exocytosis.

PMID- 22962335
TI  - Chitinophaga cymbidii sp. nov., isolated from Cymbidium goeringii roots.
AB  - Two Gram-staining-negative, aerobic, non-spore-forming rod-shaped, non-motile
      bacteria, designated strains R156-2(T) and T58-2 were isolated from the roots of
      Cymbidium goeringii. The colonies were yellow-pigmented. On the basis of 16S rRNA
      gene sequence similarity, strains R156-2(T) and T58-2 were shown to be members of
      the genus Chitinophaga. Strains R156-2(T) and T58-2 showed the greatest level of
      sequence similarity with Chitinophaga niabensis (96.0-96.3 %). The major
      menaquinone was MK-7. The main cellular fatty acids were iso-C15 : 0, C16 :
      1omega5c and iso-C17 : 0 3-OH. Phenotypic and genotypic analyses indicated that
      strains R156-2(T) and T58-2 could not be assigned to any recognized species.
      Therefore, strains R156-2(T) and T58-2 represent a novel species of the genus
      Chitinophaga, for which the name Chitinophaga cymbidii sp. nov. is proposed. The
      type strain is R156-2(T) ( = ACCC 05363(T) = KCTC 23738(T)). The DNA G+C content
      of this strain is 51.9 mol%.

PMID- 22962336
TI  - Pseudoalteromonas arabiensis sp. nov., a marine polysaccharide-producing
      bacterium.
AB  - A novel exopolysaccharide-producing bacterium, designated strain k53(T), was
      isolated from sediment from the Arabia Sea, Indian Ocean. The strain was Gram
      negative, motile, strictly aerobic, oxidase-positive and catalase-positive, and
      required Na(+) for growth. Its major isoprenoid quinone was ubiquinone-8 (Q-8),
      and its cellular fatty acid profile mainly consisted of C16 : 1omega7c, C16 : 0
      and C18 : 1omega7c. The DNA G+C content was 43 mol%. 16S rRNA gene sequence
      analysis suggested that strain k53(T) is a member of the genus Pseudoalteromonas.
      Strain k53(T) exhibited close phylogenetic affinity to Pseudoalteromonas
      lipolytica LMEB 39(T) (98.0% 16S rRNA gene sequence similarity) and
      Pseudoalteromonas donghaensis HJ51(T) (97.3 %).The DNA-DNA reassociation values
      between strain k53(T) and P. lipolytica JCM 15903(T) and P. donghaensis LMG
      24469(T) were 17 % and 12 %, respectively. Owing to the significant differences
      in phenotypic and chemotaxonomic characteristics, and phylogenetic analysis based
      on the 16S rRNA gene sequence and DNA-DNA relatedness data, the isolate merits
      classification as a representative of a novel species, for which the name
      Pseudoalteromonas arabiensis is proposed. The type strain of this species is
      k53(T) ( = JCM 17292(T) = NCIMB 14688(T)).

PMID- 22962337
TI  - A quantitative model of transcriptional differentiation driving host-pathogen
      interactions.
AB  - Despite our expanding knowledge about the biochemistry of gene regulation
      involved in host-pathogen interactions, a quantitative understanding of this
      process at a transcriptional level is still limited. We devise and assess a
      computational framework that can address this question. This framework is founded
      on a mixture model-based likelihood, equipped with functionality to cluster genes
      per dynamic and functional changes of gene expression within an interconnected
      system composed of the host and pathogen. If genes from the host and pathogen are
      clustered in the same group due to a similar pattern of dynamic profiles, they
      are likely to be reciprocally co-evolving. If genes from the two organisms are
      clustered in different groups, this means that they experience strong host
      pathogen interactions. The framework can test the rates of change for individual
      gene clusters during pathogenic infection and quantify their impacts on host
      pathogen interactions. The framework was validated by a pathological study of
      poplar leaves infected by fungal Marssonina brunnea in which co-evolving and
      interactive genes that determine poplar-fungus interactions are identified. The
      new framework should find its wide application to studying host-pathogen
      interactions for any other interconnected systems. 

PMID- 22962338
TI  - Classification of metagenomic sequences: methods and challenges.
AB  - Characterizing the taxonomic diversity of microbial communities is one of the
      primary objectives of metagenomic studies. Taxonomic analysis of microbial
      communities, a process referred to as binning, is challenging for the following
      reasons. Primarily, query sequences originating from the genomes of most microbes
      in an environmental sample lack taxonomically related sequences in existing
      reference databases. This absence of a taxonomic context makes binning a very
      challenging task. Limitations of current sequencing platforms, with respect to
      short read lengths and sequencing errors/artifacts, are also key factors that
      determine the overall binning efficiency. Furthermore, the sheer volume of
      metagenomic datasets also demands highly efficient algorithms that can operate
      within reasonable requirements of compute power. This review discusses the
      premise, methodologies, advantages, limitations and challenges of various methods
      available for binning of metagenomic datasets obtained using the shotgun
      sequencing approach. Various parameters as well as strategies used for evaluating
      binning efficiency are then reviewed.

PMID- 22962339
TI  - Metagenomic analysis: the challenge of the data bonanza.
AB  - Several thousand metagenomes have already been sequenced, and this number is set
      to grow rapidly in the forthcoming years as the uptake of high-throughput
      sequencing technologies continues. Hand-in-hand with this data bonanza comes the
      computationally overwhelming task of analysis. Herein, we describe some of the
      bioinformatic approaches currently used by metagenomics researchers to analyze
      their data, the issues they face and the steps that could be taken to help
      overcome these challenges.

PMID- 22962341
TI  - RAPHAEL: recognition, periodicity and insertion assignment of solenoid protein
      structures.
AB  - MOTIVATION: Repeat proteins form a distinct class of structures where folding is
      greatly simplified. Several classes have been defined, with solenoid repeats of
      periodicity between ca. 5 and 40 being the most challenging to detect. Such
      proteins evolve quickly and their periodicity may be rapidly hidden at sequence
      level. From a structural point of view, finding solenoids may be complicated by
      the presence of insertions or multiple domains. To the best of our knowledge, no
      automated methods are available to characterize solenoid repeats from structure.
      RESULTS: Here we introduce RAPHAEL, a novel method for the detection of solenoids
      in protein structures. It reliably solves three problems of increasing
      difficulty: (1) recognition of solenoid domains, (2) determination of their
      periodicity and (3) assignment of insertions. RAPHAEL uses a geometric approach
      mimicking manual classification, producing several numeric parameters that are
      optimized for maximum performance. The resulting method is very accurate, with
      89.5% of solenoid proteins and 97.2% of non-solenoid proteins correctly
      classified. RAPHAEL periodicities have a Spearman correlation coefficient of
      0.877 against the manually established ones. A baseline algorithm for insertion
      detection in identified solenoids has a Q(2) value of 79.8%, suggesting room for
      further improvement. RAPHAEL finds 1931 highly confident repeat structures not
      previously annotated as solenoids in the Protein Data Bank records.

PMID- 22962340
TI  - Evaluation of research in biomedical ontologies.
AB  - Ontologies are now pervasive in biomedicine, where they serve as a means to
      standardize terminology, to enable access to domain knowledge, to verify data
      consistency and to facilitate integrative analyses over heterogeneous biomedical
      data. For this purpose, research on biomedical ontologies applies theories and
      methods from diverse disciplines such as information management, knowledge
      representation, cognitive science, linguistics and philosophy. Depending on the
      desired applications in which ontologies are being applied, the evaluation of
      research in biomedical ontologies must follow different strategies. Here, we
      provide a classification of research problems in which ontologies are being
      applied, focusing on the use of ontologies in basic and translational research,
      and we demonstrate how research results in biomedical ontologies can be
      evaluated. The evaluation strategies depend on the desired application and
      measure the success of using an ontology for a particular biomedical problem. For
      many applications, the success can be quantified, thereby facilitating the
      objective evaluation and comparison of research in biomedical ontology. The
      objective, quantifiable comparison of research results based on scientific
      applications opens up the possibility for systematically improving the utility of
      ontologies in biomedical research. 

PMID- 22962342
TI  - GREVE: Genomic Recurrent Event ViEwer to assist the identification of patterns
      across individual cancer samples.
AB  - SUMMARY: GREVE has been developed to assist with the identification of recurrent
      genomic aberrations across cancer samples. The exact characterization of such
      aberrations remains a challenge despite the availability of increasing amount of
      data, from SNParray to next-generation sequencing. Furthermore, genomic
      aberrations in cancer are especially difficult to handle because they are, by
      nature, unique to the patients. However, their recurrence in specific regions of
      the genome has been shown to reflect their relevance in the development of
      tumors. GREVE makes use of previously characterized events to identify such
      regions and focus any further analysis. AVAILABILITY: GREVE is available through
      a web interface and open-source application (http://www.well.ox.ac.uk/GREVE).

PMID- 22962343
TI  - ImgLib2--generic image processing in Java.
AB  - SUMMARY: ImgLib2 is an open-source Java library for n-dimensional data
      representation and manipulation with focus on image processing. It aims at
      minimizing code duplication by cleanly separating pixel-algebra, data access and
      data representation in memory. Algorithms can be implemented for classes of pixel
      types and generic access patterns by which they become independent of the
      specific dimensionality, pixel type and data representation. ImgLib2 illustrates
      that an elegant high-level programming interface can be achieved without
      sacrificing performance. It provides efficient implementations of common data
      types, storage layouts and algorithms. It is the data model underlying ImageJ2,
      the KNIME Image Processing toolbox and an increasing number of Fiji-Plugins.
      AVAILABILITY: ImgLib2 is licensed under BSD. Documentation and source code are
      available at http://imglib2.net and in a public repository at
      https://github.com/imagej/imglib. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics Online. CONTACT: saalfeld@mpi-cbg.de

PMID- 22962344
TI  - ChemBioServer: a web-based pipeline for filtering, clustering and visualization
      of chemical compounds used in drug discovery.
AB  - SUMMARY: ChemBioServer is a publicly available web application for effectively
      mining and filtering chemical compounds used in drug discovery. It provides
      researchers with the ability to (i) browse and visualize compounds along with
      their properties, (ii) filter chemical compounds for a variety of properties such
      as steric clashes and toxicity, (iii) apply perfect match substructure search,
      (iv) cluster compounds according to their physicochemical properties providing
      representative compounds for each cluster, (v) build custom compound mining
      pipelines and (vi) quantify through property graphs the top ranking compounds in
      drug discovery procedures. ChemBioServer allows for pre-processing of compounds
      prior to an in silico screen, as well as for post-processing of top-ranked
      molecules resulting from a docking exercise with the aim to increase the
      efficiency and the quality of compound selection that will pass to the
      experimental test phase. AVAILABILITY: The ChemBioServer web application is
      available at: http://bioserver-3.bioacademy.gr/Bioserver/ChemBioServer/. CONTACT:
      gspyrou@bioacademy.gr

PMID- 22962345
TI  - Pythoscape: a framework for generation of large protein similarity networks.
AB  - Pythoscape is a framework implemented in Python for processing large protein
      similarity networks for visualization in other software packages. Protein
      similarity networks are graphical representations of sequence, structural and
      other similarities among proteins for which pairwise all-by-all similarity
      connections have been calculated. Mapping of biological and other information to
      network nodes or edges enables hypothesis creation about sequence-structure
      function relationships across sets of related proteins. Pythoscape provides
      several options to calculate pairwise similarities for input sequences or
      structures, applies filters to network edges and defines sets of similar nodes
      and their associated data as single nodes (termed representative nodes) for
      compression of network information and output data or formatted files for
      visualization.

PMID- 22962346
TI  - Comparing clustering and pre-processing in taxonomy analysis.
AB  - MOTIVATION: Massively parallel sequencing allows for rapid sequencing of large
      numbers of sequences in just a single run. Thus, 16S ribosomal RNA (rRNA)
      amplicon sequencing of complex microbial communities has become possible. The
      sequenced 16S rRNA fragments (reads) are clustered into operational taxonomic
      units and taxonomic categories are assigned. Recent reports suggest that data pre
      processing should be performed before clustering. We assessed combinations of
      data pre-processing steps and clustering algorithms on cluster accuracy for oral
      microbial sequence data. RESULTS: The number of clusters varied up to two orders
      of magnitude depending on pre-processing. Pre-processing using both denoising and
      chimera checking resulted in a number of clusters that was closest to the number
      of species in the mock dataset (25 versus 15). Based on run time, purity and
      normalized mutual information, we could not identify a single best clustering
      algorithm. The differences in clustering accuracy among the algorithms after the
      same pre-processing were minor compared with the differences in accuracy among
      different pre-processing steps. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online. CONTACT: bonder.m.j@gmail.com or
      b.brandt@acta.nl

PMID- 22962347
TI  - FetalQuant: deducing fractional fetal DNA concentration from massively parallel
      sequencing of DNA in maternal plasma.
AB  - MOTIVATION: The fractional fetal DNA concentration is one of the critical
      parameters for non-invasive prenatal diagnosis based on the analysis of DNA in
      maternal plasma. Massively parallel sequencing (MPS) of DNA in maternal plasma
      has been demonstrated to be a powerful tool for the non-invasive prenatal
      diagnosis of fetal chromosomal aneuploidies. With the rapid advance of MPS
      technologies, the sequencing cost per base is dramatically reducing, especially
      when using targeted MPS. Even though several approaches have been developed for
      deducing the fractional fetal DNA concentration, none of them can be used to
      deduce the fractional fetal DNA concentration directly from the sequencing data
      without prior genotype information. RESULT: In this study, we implement a
      statistical mixture model, named FetalQuant, which utilizes the maximum
      likelihood to estimate the fractional fetal DNA concentration directly from
      targeted MPS of DNA in maternal plasma. This method allows the improved deduction
      of the fractional fetal DNA concentration, obviating the need of genotype
      information without loss of accuracy. Furthermore, by using Bayes' rule, this
      method can distinguish the informative single-nucleotide polymorphism loci where
      the mother is homozygous and the fetus is heterozygous. We believe that
      FetalQuant can help expand the spectrum of diagnostic applications using MPS on
      DNA in maternal plasma. AVAILABILITY: Software and simulation data are available
      at http://sourceforge.net/projects/fetalquant/. CONTACT: haosun@cuhk.edu.hk.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962348
TI  - Genome-wide in silico identification of GPI proteins in Mycosphaerella fijiensis
      and transcriptional analysis of two GPI-anchored beta-1,3-glucanosyltransferases.
AB  - The hemibiotrophic fungus Mycosphaerella fijiensis is the causal agent of black
      Sigatoka (BS), the most devastating foliar disease in banana (Musa spp.)
      worldwide. Little is known about genes that are important during M. fijiensis
      Musa sp. interaction. The fungal cell wall is an attractive area of study because
      it is essential for maintenance of cellular homeostasis and it is the most
      external structure in the fungal cell and therefore mediates the interaction of
      the pathogen with the host. In this manuscript we describe the in silico
      identification of glycosyl phosphatidylinositol-protein (GPI) family in M.
      fijiensis, and the analysis of two beta-1,3-glucanosyltrans-ferases (Gas),
      selected by homology with fungal pathogenicity factors. Potential roles in
      pathogenesis were evaluated through analyzing expression during different stages
      of black Sigatoka disease, comparing expression data with BS symptoms and fungal
      biomass inside leaves. Real-time quantitative RT-PCR showed nearly constant
      expression of MfGAS1 with slightly increases (about threefold) in conidia and at
      speck-necrotrophic stage during banana-pathogen interaction. Conversely, MfGAS2
      expression was increased during biotrophy (about seven times) and reached a
      maximum at speck (about 23 times) followed by a progressive decrease in next
      stages, suggesting an active role in M. fijiensis pathogenesis.

PMID- 22962349
TI  - Bat white-nose syndrome: a real-time TaqMan polymerase chain reaction test
      targeting the intergenic spacer region of Geomyces destructans.
AB  - The fungus Geomyces destructans is the causative agent of white-nose syndrome
      (WNS), a disease that has killed millions of North American hibernating bats. We
      describe a real-time TaqMan PCR test that detects DNA from G. destructans by
      targeting a portion of the multicopy intergenic spacer region of the rRNA gene
      complex. The test is highly sensitive, consistently detecting as little as 3.3 fg
      genomic DNA from G. destructans. The real-time PCR test specifically amplified
      genomic DNA from G. destructans but did not amplify target sequence from 54
      closely related fungal isolates (including 43 Geomyces spp. isolates) associated
      with bats. The test was qualified further by analyzing DNA extracted from 91 bat
      wing skin samples, and PCR results matched histopathology findings. These data
      indicate the real-time TaqMan PCR method described herein is a sensitive,
      specific and rapid test to detect DNA from G. destructans and provides a valuable
      tool for WNS diagnostics and research.

PMID- 22962350
TI  - Physarum andinum, a new nivicolous species of myxomycete from the Patagonian
      Andes.
AB  - A new nivicolous species of Physarum was discovered during the study of
      myxomycetes in the Patagonian Andes of South America. It is described herein
      under the name Physarum andinum. The species is characterized by stalked
      sporophores or more rarely sessile sporocarps or short plasmodiocarps. The
      sporocarps are strikingly large, reaching 2.6 mm tall and 3 mm diam when open,
      and have a peridium with three layers, the internal layer being clearly visible
      and opening separately. Physarum andinum was found at five localities in
      Argentina as well as in herbarium material collected about 100 y ago in Chile.
      The new species is reminiscent of the non-nivicolous species Physarum brunneolum,
      but the latter forms smaller sporophores, has darker spores and the three layers
      of the peridium are adhered and open together. The characters of the new species
      were examined under stereomicroscope, light microscope and scanning electron
      microscope and micrographs of relevant details are included.

PMID- 22962351
TI  - Species-abundance distribution patterns of soil fungi: contribution to the
      ecological understanding of their response to experimental fire in Mediterranean
      maquis (southern Italy).
AB  - Experimental fires, of both low and high intensity, were lit during summer 2000
      and the following 2 y in the Castel Volturno Nature Reserve, southern Italy. Soil
      samples were collected Jul 2000-Jul 2002 to analyze the soil fungal community
      dynamics. Species abundance distribution patterns (geometric, logarithmic, log
      normal, broken-stick) were compared. We plotted datasets with information both on
      species richness and abundance for total, xerotolerant and heat-stimulated soil
      microfungi. The xerotolerant fungi conformed to a broken-stick model for both the
      low- and high intensity fires at 7 and 84 d after the fire; their distribution
      subsequently followed logarithmic models in the 2 y following the fire. The
      distribution of the heat-stimulated fungi changed from broken-stick to
      logarithmic models and eventually to a log-normal model during the post-fire
      recovery. Xerotolerant and, to a far greater extent, heat-stimulated soil fungi
      acquire an important functional role following soil water stress and/or fire
      disturbance; these disturbances let them occupy unsaturated habitats and become
      increasingly abundant over time.

PMID- 22962352
TI  - Biology, ecology and ultrastructure of Ascobotryozyma and Botryozyma, unique
      commensal nematode-associated yeasts.
AB  - Ascobotryozyma (anamorph Botryozyma) is an ascomycetous yeast genus characterized
      by its unusual morphology and ability to attach to free-living nematodes in the
      genus Panagrellus. Other than species descriptions for four taxa little is known
      about these yeasts. Investigations were carried out to determine the ecological
      relationship and specificity with nematodes in addition to examining basic cell
      structure, thallus development and sexual reproduction. Based on previous
      examinations of the yeast and nematode it was hypothesized the fungus did not
      parasitize the nematode but instead remained attached to nematodes for dispersal.
      Electron micrographs supported our hypotheses and revealed a specialized cell
      wall and mucilage that aid in attachment to the nematode cuticle. Tests to
      determine the ability of Ascobotryozyma and Botryozyma to attach to different
      nematode taxa revealed that attachment varies across taxonomic groups.
      Examinations of thallus cells, thallus growth, cell fusion and ascosporogenesis
      are presented. This study provides insight into an otherwise cryptic yeast genus.

PMID- 22962354
TI  - Multiplex PCR analysis of fumonisin biosynthetic genes in fumonisin-nonproducing
      Aspergillus niger and A. awamori strains.
AB  - To determine the genetic basis for loss of fumonisin B2 (FB2) biosynthesis in FB2
      nonproducing Aspergillus niger and A. awamori strains, we developed multiplex PCR
      primer sets to amplify fragments of eight fumonisin biosynthetic pathway (fum)
      genes. Fragments of all eight fum genes were amplified from FB2-producing A.
      niger and A. awamori strains; from FB2-nonproducing strains four amplification
      patterns arose in which one or more fum gene fragments were absent. Southern
      hybridization analysis of strains yielding patterns 2 and 3 confirmed that loss
      of FB2 production in A. awamori is associated with gene deletions within the
      fumonisin biosynthetic gene cluster. In addition, we observed a fifth multiplex
      amplification pattern in which all eight fum gene fragments appeared. Reverse
      transcription-PCR analysis of strains yielding pattern 5 showed that the
      expression of at least one fum gene was reduced relative to expression in FB2
      producing A. niger. This suggests that in these strains loss of FB2 production is
      a result of structural or regulatory mutations that alter gene expression or
      function. These results demonstrate a diversity of genotypes within FB2
      nonproducing A. niger and A. awamori populations and provide tools useful for
      identifying certain non-toxigenic strains for industrial or ecological
      applications.

PMID- 22962355
TI  - Combined molecular and morphological data for improving phylogenetic hypothesis
      in Dacrymycetes.
AB  - We analyzed the DNA sequences of four gene regions, 28S and 18S rDNA, the ITS
      region and rpb2, to obtain a high resolution phylogenetic tree of Dacrymycetes.
      In addition, we comparatively studied micro- and macromorphological
      characteristics of representative species. The traditional generic classification
      based on morphological characteristics was not reflected by our molecular
      phylogenies. Ancestral state reconstructions indicated that the morphology of
      basidia and clamp connections are evolutionarily stable. In contrast,
      basidiocarps and basidiospore septation patterns appear variable. Dacrymyces
      unisporus shares the dolipores with non-perforate parenthesomes typical of other
      dacrymycetous taxa but is a unique species having predominantly non-bifurcate
      basidia and subglobose to ovoid basidiospores with transverse and longitudinal
      septa. In molecular phylogenies this species is a member of Dacrymycetes but
      always occupies a sister position in relation to the rest of the Dacrymycetes.
      Based on our results we propose a new genus, Unilacryma, for D. unisporus. For
      proper accommodation of this taxon, we introduce the family Unilacrymaceae and
      the order Unilacrymales. 

PMID- 22962356
TI  - A common new species of Inocybe in the Pacific Northwest with a diagnostic PDAB
      reaction.
AB  - A species of Inocybe common in Washington, Oregon and British Columbia is
      documented and described as new. The species, I. chondroderma, is characterized
      by these features: pileus with a fulvous disk and ochraceous to chamois margin,
      presence of a cortina, densely mycelioid stipe base, smooth spores and fall
      phenology. The most reliable and distinctive feature of the species is a blue
      green or turquoise reaction in response to application of a solution of p
      dimethylaminobenzaldehyde (PDAB), indicating the presence of what is most likely
      an indole alkaloid. PDAB use provides a quick and diagnostic character easily
      implemented in a laboratory setting. ITS sequences from recent collections of I.
      chondroderma and from materials collected in the 1940s in Washington and Oregon
      fully match numerous mislabeled sequences from specimens in British Columbia and
      Oregon. The species is most closely related to an unclarified taxon from Colorado
      and Japan (I. cf. chondroderma) and a rare European species, I. subnudipes. Nine
      different species names in Inocybe and one in Hebeloma attributed to I.
      chondroderma based on GenBank BLASTN searches of the ITS locus match with 99-100%
      similarity, reinforcing concerns about taxonomic inaccuracies in public DNA
      sequence databases. A complete morphological description, illustrations and
      phylogenetic assessment are provided.

PMID- 22962357
TI  - The double life of Ceratobasidium: orchid mycorrhizal fungi and their potential
      for biocontrol of Rhizoctonia solani sheath blight of rice.
AB  - Ceratobasidium includes orchid mycorrhizal symbionts, plant pathogens and
      biocontrol agents of soilborne plant pathogens. It is not known to what extent
      members of the first guild also can participate in the others. Ceratobasidium
      spp. were isolated from roots of Colombian orchids and identified by phylogeny
      based on nrITS sequences. Phylogenetic grouping of Ceratobasidium spp. isolates
      corresponded to orchid host substrate (epiphytic vs. terrestrial). Isolates were
      tested for virulence on rice and for biocontrol of Rhizoctonia solani, causal
      agent of sheath blight of rice. All Ceratobasidium spp. isolates caused some
      signs of sheath blight but significantly less than a pathogenic R. solani used as
      a positive control. When Ceratobasidium spp. isolates were inoculated on rice
      seedlings 3 d before R. solani, they significantly reduced disease expression
      compared to controls inoculated with R. solani alone. The use of Ceratobasidium
      spp. from orchids for biological control is novel, and biodiverse countries such
      as Colombia are promising places to look for new biocontrol agents.

PMID- 22962358
TI  - Farnesol induces apoptosis-like phenotype in the phytopathogenic fungus Botrytis
      cinerea.
AB  - This study demonstrates that the isoprenoid farnesol produces a toxic effect on
      the phytopathogenic fungus Botrytis cinerea in solid and liquid media. In solid
      media farnesol retarded 72 h the beginning of mycelial growth. Also, it was
      demonstrated that the toxic effect is due to farnesol triggers apoptosis in B.
      cinerea because ROS accumulation, DNA fragmentation and phosphatidylserine
      externalization were detected in farnesol-treated mycelium. Therefore, compounds
      that increase the intracellular farnesol or induce apoptosis could have a
      potential application as fungicide against B. cinerea.

PMID- 22962359
TI  - The phylogenetic position of Postia s.l. (Polyporales, Basidiomycota) from
      Patagonia, Argentina.
AB  - We investigated the phylogenetic relationships of Postia species from Patagonia
      with rDNA ITS and LSU sequences, together with morphological, cultural and
      biological features. All species in the genus were included in a "Postia clade"
      irrespective of whether their spores were thin- or thick-walled. This clade is
      characterized by tetrapolar mating, a normal nuclear behavior, metachromatic
      generative hyphae and absence of fiber hyphae in culture. One subclade merged the
      austral taxa P. pelliculosa and P. punctata, but otherwise no distinct
      relationships were found regarding spore shape, spore wall thickness and
      geographical distribution of taxa. The austral P. venata and the endemic P.
      carbophila, with thin-walled basidiospores, occupied variable positions in both
      analyses. Postia caesia from Patagonia grouped within the P. caesia species
      complex but on a separate branch. In contrast, P. rennyi and P. balsamea from
      Patagonia corresponded well with strains from other geographic areas. The two
      austral species in Ryvardenia, R. cretacea and R. campyla, characterized by non
      metachromatic hyphae, bipolar mating and an astatocoenocytic nuclear behavior,
      formed an independent subclade among the dimitic genera of the "Antrodia clade",
      far from other Postia taxa within which they had been placed previously,
      supporting their inclusion in a genus of their own. Postia carbophila grouped
      with other Postia species and not with Postia (Rhodonia) placenta as suggested
      previously on the basis of morphological comparisons. Instead, the latter species
      grouped with taxa in the dimitic genus Amyloporia with which it shares
      heterocytic nuclear behavior. A separation between specimens of Postia
      pelliculosa and Ryvardenia cretacea from either side of the Pacific (i.e. SE
      Australia/New Zealand and S Argentina/S Chile) suggests they could be considered
      different at the species level from a phylogenetic point of view.

PMID- 22962353
TI  - New North American truffles (Tuber spp.) and their ectomycorrhizal associations.
AB  - Recent surveys of belowground fungal biodiversity in Mexico and USA have revealed
      many undescribed truffle species, including many in the genus Tuber. Here we
      describe seven new species: Tuber beyerlei, T. castilloi, T. guevarai, T. lauryi,
      T. mexiusanum, T. miquihuanense and T. walkeri. Phylogenetic analyses place these
      species within the Maculatum group, an understudied clade of small truffles with
      little apparent economic value. These species are among the more taxonomically
      challenge-ing in the genus. We collected Tuber castilloi, T. mexiusanum and T.
      guevarai as fruit bodies and ectomycorrhizae on Quercus spp. in forests of
      eastern Mexico. Tuber mexiusanum has a particularly broad geographic range, being
      collected in eastern USA under Populus deltoides and in Minnesota and Iowa in
      mixed hardwood forests. T. walkeri is described from the upper midwestern USA,
      and T. lauryi and T. beyerlei occur in the western USA.

PMID- 22962360
TI  - Cortinarius section Sanguinei in North America.
AB  - The North American species of Cortinarius section Sanguinei were studied using
      morphological characters and ITS and RPB2 sequence data. Several type collections
      also were examined. Four species were identified: C. harrisonii sp. nov, C.
      neosanguineus sp. nov., C. sanguineus and C. sierraensis comb. nov. Of these, C.
      sanguineus also occurs in Europe together with C. puniceus, a fifth member of the
      section. Typical features of these species include +/- red, fairly small
      basidiomata, stipe basal mycelium often with yellow to reddish yellow tints,
      amygdaloid to ellipsoid spores, and aniline-red lamellar trama and pileipellis
      hyphae when mounted in KOH. Two other species with red lamellae C. marylandensis
      comb. nov. and C. smithii stat. nov. & nom. nov. also are discussed.

PMID- 22962361
TI  - Modelling and simulating generic RNA-Seq experiments with the flux simulator.
AB  - High-throughput sequencing of cDNA libraries constructed from cellular RNA
      complements (RNA-Seq) naturally provides a digital quantitative measurement for
      every expressed RNA molecule. Nature, impact and mutual interference of biases in
      different experimental setups are, however, still poorly understood-mostly due to
      the lack of data from intermediate protocol steps. We analysed multiple RNA-Seq
      experiments, involving different sample preparation protocols and sequencing
      platforms: we broke them down into their common--and currently indispensable-
      technical components (reverse transcription, fragmentation, adapter ligation, PCR
      amplification, gel segregation and sequencing), investigating how such different
      steps influence abundance and distribution of the sequenced reads. For each of
      those steps, we developed universally applicable models, which can be
      parameterised by empirical attributes of any experimental protocol. Our models
      are implemented in a computer simulation pipeline called the Flux Simulator, and
      we show that read distributions generated by different combinations of these
      models reproduce well corresponding evidence obtained from the corresponding
      experimental setups. We further demonstrate that our in silico RNA-Seq provides
      insights about hidden precursors that determine the final configuration of reads
      along gene bodies; enhancing or compensatory effects that explain apparently
      controversial observations can be observed. Moreover, our simulations identify
      hitherto unreported sources of systematic bias from RNA hydrolysis, a
      fragmentation technique currently employed by most RNA-Seq protocols.

PMID- 22962362
TI  - Impact of intensity versus duration of cycling on coronary disease mortality.

PMID- 22962363
TI  - Progesterone and stroke recovery: a match ultimately won by survivin?

PMID- 22962364
TI  - Complete viral RNA genome sequencing of ultra-low copy samples by sequence
      independent amplification.
AB  - RNA viruses are the causative agents for AIDS, influenza, SARS, and other serious
      health threats. Development of rapid and broadly applicable methods for complete
      viral genome sequencing is highly desirable to fully understand all aspects of
      these infectious agents as well as for surveillance of viral pandemic threats and
      emerging pathogens. However, traditional viral detection methods rely on prior
      sequence or antigen knowledge. In this study, we describe sequence-independent
      amplification for samples containing ultra-low amounts of viral RNA coupled with
      Illumina sequencing and de novo assembly optimized for viral genomes. With 5
      million reads, we capture 96 to 100% of the viral protein coding region of HIV,
      respiratory syncytial and West Nile viral samples from as little as 100 copies of
      viral RNA. The methods presented here are scalable to large numbers of samples
      and capable of generating full or near full length viral genomes from clone and
      clinical samples with low amounts of viral RNA, without prior sequence
      information and in the presence of substantial host contamination.

PMID- 22962366
TI  - Mesenteric cyst: drained and marsupialised laparoscopically avoiding enterectomy.

PMID- 22962365
TI  - Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine DNA
      glycosylase domain: its structural basis and implications for active DNA
      demethylation.
AB  - The mammalian thymine DNA glycosylase (TDG) is implicated in active DNA
      demethylation via the base excision repair pathway. TDG excises the mismatched
      base from G:X mismatches, where X is uracil, thymine or 5-hydroxymethyluracil
      (5hmU). These are, respectively, the deamination products of cytosine, 5
      methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). In addition, TDG excises
      the Tet protein products 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) but
      not 5hmC and 5mC, when paired with a guanine. Here we present a post-reactive
      complex structure of the human TDG domain with a 28-base pair DNA containing a
      G:5hmU mismatch. TDG flips the target nucleotide from the double-stranded DNA,
      cleaves the N-glycosidic bond and leaves the C1' hydrolyzed abasic sugar in the
      flipped state. The cleaved 5hmU base remains in a binding pocket of the enzyme.
      TDG allows hydrogen-bonding interactions to both T/U-based (5hmU) and C-based
      (5caC) modifications, thus enabling its activity on a wider range of substrates.
      We further show that the TDG catalytic domain has higher activity for 5caC at a
      lower pH (5.5) as compared to the activities at higher pH (7.5 and 8.0) and that
      the structurally related Escherichia coli mismatch uracil glycosylase can excise
      5caC as well. We discuss several possible mechanisms, including the amino-imino
      tautomerization of the substrate base that may explain how TDG discriminates
      against 5hmC and 5mC.

PMID- 22962367
TI  - Malignant pericardial effusion in a patient with prostate adenocarcinoma.
AB  - The authors discuss a rare case of pericardial effusion secondary to carcinoma of
      the prostate. A month after therapeutic pericardiocentesis there was a
      haemodynamically significant recurrence, necessitating a pericardial window. The
      authors discuss pericardial effusion and the management of such patients.

PMID- 22962368
TI  - An unusual intradural involvement secondary to Burkitt's lymphoma.

PMID- 22962369
TI  - Ganfort, a blinding drug to the physician.
AB  - Ganfort eye drops are indicated for adult patients with open-angle glaucoma who
      have poor response to topical beta-blockers or prostaglandin analogues. They
      contain 0.3 mg of bimatoprost (a prostaglandin) and 5 mg of timolol (beta
      blocker). The authors present a case of a 45-year-old man with glaucoma
      presenting with shortness of breath. On admission, he had a normal heart rate,
      pulse oximetry and examination. Despite being of low risk stratification using
      the Wells score and the Modified Geneva Score for pulmonary emboli, CT pulmonary
      angiogram scan subsequently showed extensive bilateral multiple large pulmonary
      emboli. This case demonstrates that the systemic absorption of ocular beta
      blockers is extremely high and it bypasses the first pass metabolism. Therefore,
      even one drop of Ganfort into each eye once a day was sufficient to disguise the
      tachycardia of a large pulmonary emboli.

PMID- 22962370
TI  - A rare complication of suprapubic catheterisation following pelvic reconstructive
      surgery for urinary incontinence.
AB  - Suprapubic (SP) catheterisation is commonly used for drainage of the bladder
      following pelvic surgery. Although it is a widely employed procedure, it is not
      without complications, such as infection and blockage. The authors report a rare
      complication of SP catheterisation involving a persistent SP catheter site
      fistulous tract and an infected haematoma significantly complicating a patient's
      postoperative course. Wound debridement, bladder drainage and a prolonged course
      of antibiotics were employed to successfully treat this complication. The exact
      mechanism of her complication is only speculative, however to our knowledge no
      similar cases of a fistula after removal of a SP catheter used for short-term
      bladder drainage have been reported.

PMID- 22962371
TI  - An unusual cause of gross abdominal distension in a 59-year-old man: huge
      mesenteric cyst.

PMID- 22962372
TI  - An unusual cure for acromegaly.
AB  - The authors present the case of a 30-year-old female patient with acromegaly
      whose disease had not been cured after transcranial neurosurgery, two
      transsphenoidal surgeries and stereotactic radiosurgery. She required treatment
      with octreotide and pegvisomant to normalise growth hormone levels. Seven years
      after the diagnosis of acromegaly, she noticed acute vision loss in her left eye
      and presented with meningism. She had an intrasellar abscess which was confirmed
      and treated by surgical drainage. As a result of the abscess, she was cured of
      acromegaly and able to discontinue both octreotide and pegvisomant.

PMID- 22962373
TI  - Bilateral botryoid nephroblastoma: a rare cause of renal failure.
AB  - The authors describe the case of a 16-month-old girl who presented with bilateral
      hydronephrosis and renal failure secondary to bilateral renal pelvic botryoid
      Wilms' tumour (nephroblastoma). The term 'botryoid' describes an intrapelvic
      polypoid renal Wilms tumour, either extending from the renal parenchyma or
      primarily pelvis-based tumour. Both tumours filled the renal pelvis and extended
      down the proximal ureter, with no intraparenchymal tumour seen. Bilateral
      intralobar nephrogenic rests were present. Histological examination demonstrated
      triphasic nephroblastoma, with focal rhabdomyomatous differentiation of the
      stromal element bilaterally. Postchemotherapy, the patient underwent bilateral
      nephrectomy. Post complete resection of her bilateral disease, this patient has
      had an excellent outcome. This is only the third reported case of bilateral
      botryoid Wilms' tumour. While the condition is extremely rare, it should be
      included in the differential diagnosis of a young child with bilateral renal
      pelvic masses.

PMID- 22962374
TI  - Barium aspiration.

PMID- 22962375
TI  - A rare case of polyorchidism.
AB  - A 28-year-old offshore worker attended accident and emergency department with a
      tender benign-feeling lump inferior to the left testis. He was previously
      investigated abroad with an ultrasound scan showing a homogenous mass posterior
      to the left testis. Subsequent CT was unremarkable. As there was no clinical
      suspicion of malignancy, a scrotal exploration was performed. During scrotal
      exploration, the left testicular mass appeared to be a supernumerary testis,
      which shared the same tunica albuginea. Histology has confirmed the diagnosis.
      Polyorchidism is an extremely rare congenital anomaly, and can be associated with
      hydrocele, testicular torsion or rarely malignancy. Leung has classified
      polyorchidism in four types. This case has been described as type 2; the
      supernumerary testis shares the epididymis and the vas deferens of the other
      testis. Treatment can either be conservative or surgical excision. However, if
      the supernumerary testis is asymptomatic, with negative tumour markers and
      radiological findings, surgery can be avoided.

PMID- 22962376
TI  - Strangulated inguinal hernia presenting as haemoperitoneum.
AB  - A 57-year-old man presented with abdominal pain following a collapse, with
      peritonism in his lower abdomen. He was haemodynamically stable, with haemoglobin
      of 12.6 g/dl. His significant medical history included open bilateral inguinal
      hernia repairs. CT demonstrated fluid within the abdominal cavity, and an area of
      stranding lying medially within the left iliac fossa. Ultra-sound guided fluid
      aspiration demonstrated frank blood. During admission, the patient noted a
      recurrence of his left inguinal hernia. Laparotomy revealed haemoperitoneum, and
      a haematoma arising in the left iliac fossa, walled off by mesentery of the
      sigmoid colon and adherent omentum. The open repair of the recurrent inguinal
      hernia identified the sac contents to be similar to the omentum. This association
      implies the omentum had herniated within the inguinal canal, tore or avulsed,
      resulting in haemorrhage from the proximal omental blood vessel resulting in
      haemoperitonism.

PMID- 22962377
TI  - A misplaced window.

PMID- 22962378
TI  - Pro-coaguable states lead to a sticky situation: coronary saddle embolism in a
      patient with known hypertrophic cardiomyopathy and atrial fibrillation.

PMID- 22962379
TI  - A rare cause of lower GI bleeding.
AB  - The authors present a rare case of lower gastrointestinal (GI) bleed due to GI
      amyloidosis secondary to multiple myeloma. A 79-year-old lady who presented with
      bloody diarrhoea for 4 weeks. Flexible sigmoidoscopy showed slight oedematous
      mucosa extending up to the sigmoid colon. CT abdomen showed lytic lesions in the
      vertebral bodies. 24 h protein analysis and serum electrophoresis suggestive of
      multiple myeloma, which was confirmed with bone marrow biopsy, revealed plasma
      cell myeloma.

PMID- 22962381
TI  - Nasal tooth: an unusual cause of nasal obstruction and sinusitis.

PMID- 22962382
TI  - Infant botulism following honey ingestion.
AB  - An apparently well baby girl born at term was presented with signs and symptoms
      suggestive of acute onset of generalised floppiness at the age of 3 months.
      Clinically, the baby had lower motor neuron type of muscle weakness; detailed
      investigation lead to the diagnosis of neuromuscular junction disorder secondary
      to botulism toxicity. Further tests confirmed the botulism toxicity secondary to
      honey ingestion. The baby was treated with specific anticlostridium antibodies;
      she recovered remarkably, now growing and developing normally.

PMID- 22962380
TI  - Cryptococcal osteomyelitis and meningitis in a patient with non-hodgkin's
      lymphoma treated with PEP-C.
AB  - The authors present the first case report of a patient with lymphoma who
      developed disseminated cryptococcal osteomyelitis and meningitis while being
      treated with the PEP-C (prednisone, etoposide, procarbazine and cyclophosphamide)
      chemotherapy regimen. During investigation of fever and new bony lesions, fungal
      culture from a rib biopsy revealed that the patient had cryptococcal
      osteomyelitis. Further evaluation demonstrated concurrent cryptococcal
      meningitis. The patient's disseminated cryptococcal infections completely
      resolved after a full course of antifungal treatment. Cryptococcal osteomyelitis
      is itself an extremely rare diagnosis, and the unique presentation with
      concurrent cryptococcal meningitis in our patient with lymphoma was likely due to
      his PEP-C treatment. It is well recognised that prolonged intensive
      chemotherapeutic regimens place patients at risk for atypical infections; yet
      physicians should recognise that even chronic low-dose therapies can put patients
      at risk for fungal infections. Physicians should consider fungal infections as
      part of the infectious investigation of a lymphopaenic patient on PEP-C.

PMID- 22962384
TI  - Pulmonary amyloidosis--an unusual cause of chest pain.

PMID- 22962383
TI  - Sensory trick with metoclopramide-associated tardive tremor.
AB  - Tardive tremor is a 3-5 Hz bilateral resting and action tremor, associated with
      the use of dopamine receptor blocking drugs, accompanied by other tardive
      movement disorders and responsive to tetrabenazine or clozapine. We describe a
      case of a sensory trick associated with tardive tremor which raises important
      points about semiology and management. First, the presence of a sensory trick
      with tardive limb tremor suggests that the disorder may be a form of dystonia.
      Second, further study of osteopathic manipulative therapy for treatment of
      dystonia or tardive tremor is supported by a symptomatic response observed in our
      case.

PMID- 22962385
TI  - Pulmonary embolus as a first presentation of occult metastatic prostate cancer.
AB  - A 65-year-old gentleman with a previous history of pulmonary embolus presented
      with a subacute onset of shortness of breath, haemoptysis and chest pain
      associated with a swollen left leg. Ultrasound Doppler scanning of the leg
      revealed no deep-vein thrombosis. Thereafter, a CT scan of the pulmonary
      vasculature revealed a large right-sided pulmonary embolus. CT scanning of the
      abdomen and pelvis was performed to look for evidence of an intra-abdominal
      source of thrombus and revealed evidence of a moderate sized pelvic mass causing
      obstructive uropathy. Urological review of the patient revealed a hard prostate
      and raised prostate specific antigen, consistent with a diagnosis of primary
      prostatic carcinoma, which after investigation with a radioisotope bone scan was
      found to have metastasised to the bony pelvis.

PMID- 22962386
TI  - Idiopathic pulmonary thromboembolism in the course of intensive psychiatric
      inpatient care: case report and treatment guidelines.
AB  - Idiopathic thromboembolism can occur in psychiatric patients who have been
      inactive during a period of inpatient hospital treatment. These patients are
      usually treated with antipsychotic medication which has also been reported to
      increase risk for thromboembolic disease. Here the authors describe a patient
      with neither prior history of thromboembolism nor any medical risk factors for
      thromboembolic disease, who was admitted with an acute relapse of psychotic
      illness. During the course of her intensive psychiatric treatment, she had chest
      pain and CT-pulmonary arteriogram revealed bilateral lower lobe pulmonary
      embolism. She was anticoagulated and made a full medical recovery. Treatment with
      high dosages of typical and atypical antipsychotic medication and a lack of
      mobility related to intensive nursing care and sedation were likely risk factors
      in her development of pulmonary emboli.

PMID- 22962387
TI  - Scorpion sting: eclampsia.
AB  - Scorpion stings are common in many regions of the world, particularly in rural
      areas. While most of the stings are harmless and tend to be milder, some stings
      rarely have severe clinical course, including neurological, cardiovascular and
      respiratory system complications. Although there are many studies in the
      literature related to the scorpion sting, data on effects of scorpion stings in
      pregnant woman are very little. The authors have not come across any case report
      of eclampsia as a complication of scorpion sting. With this study, the authors
      aimed to discuss a scorpion sting lead to an unexpected complication, eclampsia.

PMID- 22962388
TI  - Clostridium septicum sepsis and its implications.
AB  - An elderly gentleman, who had 12 years earlier been successfully treated for
      colon cancer, presented with fever, rigours, right upper quadrant abdominal pain
      and tenderness. A CT of the abdomen revealed a colonic mass distal to the hepatic
      flexure with multiple gas locules and a walled off perforation. He underwent a
      right hemicolectomy. Histology confirmed multifocal colonic adenocarcinoma. His
      admission blood cultures grew Clostridium septicum. A week postoperatively he
      developed intermittent fevers and abdominal pain. Repeat CT revealed an abdominal
      collection adjacent to the new anastomosis, but more importantly, a sharply
      shouldered aneurysmal dilation of the infra-renal abdominal aorta. These findings
      prompted immediate surgical drainage of the collection, repair of the
      anastomostic leak, resection of the infected aortic aneurysm and replacement with
      a tube graft. This case highlights the clinical significance of C septicum
      bacteraemia: its association with occult colonic malignancy and with mycotic
      aneurysm formation. Clostridia isolated from blood cultures should not be
      dismissed as contaminants but fully identified to ensure appropriate patient
      management.

PMID- 22962389
TI  - Atrial myxoma: a rare cause of cardioembolic stroke.
AB  - The authors present the case of a 45-year-old lady who presented to the emergency
      department with sudden onset of right hemiparesis, numbness, dysarthria,
      dysmetria, left upper motor neuron facial palsy and left extensor plantar.
      Initial laboratory investigations, ECG and MR angiography were normal. MRI brain
      revealed multiple ischaemic strokes in middle cerebral artery and posterior
      cerebral artery territory. Transthoracic echocardiography revealed large mobile
      mass in left atrium which was resected and the patient remained well
      postoperatively. Anticoagulants do not play any protective role making resection
      as the only effective treatment.

PMID- 22962390
TI  - An uncommon anatomy presenting with a common disease.
AB  - Coronary artery fistulas are rare anomalous communications, between coronary
      arteries and cardiac chambers and great vessels. They are often congenital, but
      usually present in adulthood. They can affect cardiac haemodynamic stability and
      are thought to predispose patients to heart failure, myocardial ischaemia,
      myocardial infarction, infective endocarditis, arrythmias and rupture. Herein, a
      case is discussed where a patient with long-standing stable angina was found to
      have a coronary artery fistula to the main pulmonary artery and concomitant
      ischaemic heart disease with a chronically occluded left anterior descending
      artery, proximal to the fistula. It is thought that the fistula probably
      predisposed the patient's ischaemic heart disease. He underwent a successful
      coronary artery bypass grafting plus surgical ligation of the coronary artery
      fistula. This uncommon coronary artery anomaly, presenting with ischaemic heart
      disease, a common disease in adulthood, is discussed in the context of current
      recommedations.

PMID- 22962391
TI  - Spontaneous gastric perforation in an 11-year-old boy with anorexia nervosa: rare
      presentation with right iliac fossa pain.
AB  - Spontaneous gastric perforation is rare in children. It is usually associated
      with prematurity, foreign bodies and trauma. Anorexia nervosa (AN) can be an
      underlying condition although no cases are reported in the literature. We are
      reporting a rare case of 1-year-old boy with AN who presented with right iliac
      fossa (RIF) pain mimicking acute appendicitis. Intraoperative findings proved a
      gastric perforation. Pathophysiology of this condition in AN is poorly
      understood. Gastric smooth muscle atrophy and ischaemia can be the possible
      underlying mechanisms. The case discussed here highlights the fact that any
      abdominal pain in patients with underlying eating disorders (EDs) should raise
      suspicion of perforation as diagnosis can be far more complicated.

PMID- 22962392
TI  - Osteogenesis imperfecta with right renal artery occlusion.
AB  - We here report a case of osteogenesis imperfecta who presented with severe
      hypertension and left ventricular failure and had right renal artery occlusion.
      The case is very interesting as renal artery occlusion has not been reported
      earlier in osteogenesis imperfecta.

PMID- 22962393
TI  - Complicated appearance of an abdominal mass in the I-131 MIBG and Tc-99m bone
      scintigraphy of a patient with neuroblastoma.
AB  - Neuroblastoma is a common childhood neoplasia arising from neurogenic tissues.
      Main symptoms of this disease are bone pain, fewer, weight loss and anaemia. I
      131 metaiodobenzylguanidine (MIBG) is a highly sensitive and specific method in
      the detection of this disease and method of choice in staging, treatment response
      and recurrence detection as well as prognostification. In determination of the
      bone metastasis Tc-99m methylenediphosphonate (MDP) bone scintigraphy should be
      included to staging protocol. Abdominal masses originated from neurogenic tissues
      (neuroblastoma) can accumulate Tc-99m MDP. We want to present a child with
      neuroblastoma and abdominal mass displacing the adjacent kidney and accumulating
      both I-131 MIBG and Tc-99m MDP.

PMID- 22962394
TI  - A rare congenital neck lump.
AB  - We describe the case and present a radiological image of a neck lump identified
      antenatally with ultrasound imaging. Postnatally a left-sided asymptomatic neck
      lump was identified in the left posterior triangle of the neck. Repeat ultrasound
      and CT imaging were arranged confirming a cyst adjacent to the cervical
      oesophagus and displacing the carotid sheath anteriorly. Complete cyst excision
      was achieved with no complications. Histological analysis identified a 30*22*20
      mm cyst with a smooth muscle layer within the cyst wall and a lining of
      respiratory epithelium. These findings were consistent with a diagnosis of
      cervical duplication cyst (CDC). Proximity to the carotid sheath and oesophagus
      can make CDC excision potentially dangerous hence preoperative CT scanning was
      useful to establish the anatomical relations of the cyst in this case.

PMID- 22962395
TI  - A right inguinoscrotal swelling: the importance of histological analysis.
AB  - Myxofibrosarcoma of the spermatic cord is a rare condition. We present an unusual
      case of a 69-year-old gentleman who presented to the emergency department on two
      occasions with a right inguinoscrotal swelling. We will explore the diagnostic
      difficulties encountered and subsequent management. We will also highlight the
      importance of histological analysis when unexpected findings are encountered.

PMID- 22962396
TI  - Use of cautery as a therapeutic modality in skin metastasis due to renal cell
      carcinoma.
AB  - Renal cell carcinoma commonly metastasises to the lungs, lymphatics and bone; it
      uncommonly metastasises to the skin. Several studies and reports have noted skin
      metastasis to be an indicator of high death rates. The best treatment for a
      single skin metastasis is surgical excision. However, local radiotherapy has been
      found to be equally effective. We present a case report where cautery was used at
      the site of skin metastasis, with good results.

PMID- 22962397
TI  - Imported melioidosis in France revealed by a cracking abdominal mycotic aortic
      aneurysm in a 61-year-old man.

PMID- 22962398
TI  - Psoas abscess secondary to haematoma after a fall causing multiple osteoporotic
      fractures.
AB  - A 78-year-old woman presented 28 days after a low-impact fall, where she
      sustained a right pubic ramus fracture, with increasing left hip pain and fever.
      Her blood results showed a high white cell count and deranged urea and
      electrolytes. An MRI revealed multiple osteoporotic fractures and bilateral
      gluteal abscesses with left iliopsoas abscess, which had likely formed in a
      haematoma of a sacral fracture. She received a long course of intravenous
      antibiotics and CT-guided drainage of the abscesses. She developed symptoms of
      cauda equina, but no evidence of epidural extension of the abscess was found at
      operation. She required neurorehabilitation. This case highlights the
      complications of pelvic osteoporotic fractures, and high associated morbidity and
      mortality in the elderly population.

PMID- 22962399
TI  - 'Non-resolving' pneumonia.
AB  - A 47-year-old man presented with symptoms of fever and productive cough secondary
      to a left upper lobe pneumonia. He had received more than three courses of
      antibiotics over a 2-year period. Review of serial radiographic exams including
      chest x-ray and CT scans revealed consolidation of the left upper lobe. Lack of
      response to antibiotics prompted invasive testing with bronchoscopy which
      revealed a growth in the left main bronchus. Histopathology revealed squamous
      cell carcinoma.

PMID- 22962400
TI  - Thrombolysis in anterior spinal artery syndrome.
AB  - Anterior spinal artery syndrome (ASAS) is often a devastating spinal stroke
      occurring when the anterior spinal artery or one of its supplying anterior
      medullary arteries are occluded. The most common causes are arteriosclerosis,
      dissection of the abdominal aorta, cardiac embolism and degenerative spine
      disease, and the major risk factors are smoking, hypertension, diabetes and
      hypercholesterolaemia. The treatment has generally been supportive. We believe
      thrombolysis should be considered in the acute phase of this condition, and
      present a case with ASAS who experienced partial recovery after treatment given
      4.5 h after symptom onset.

PMID- 22962401
TI  - Increased frequency of headache and change in visual aura due to occipital
      cysticercus granuloma.
AB  - Migraine is a common clinical disorder, quite disabling and affecting the quality
      of life in majority of patients. The visual aura is the commonest among all types
      of aura. Various types of migraine aura described in the literature are
      photopsia, fortification spectra, scotoma, visual distortion, haemianopia and
      metamorphsia. The epileptic visual aura differs from aura associated with
      migraine in certain features: short lasting for 2-3 minutes, occurring in
      clusters, multicoloured and circular in shape. The ictal manifestations of
      occipital lobe lesions can mimic episodes of migraine with visual aura according
      to some reports. In this case report, we intended to highlight aggravation and
      increased frequency of headache attacks and changed pattern of aura induced by
      occipital lobe cysticercus granuloma in a patient diagnosed of migraine with
      aura. The importance of neuroimaging of brain in state of unexpected increased
      frequency of headache episodes has been emphasised.

PMID- 22962402
TI  - Evolution of entero-biliary fistula following gallstone ileus management.

PMID- 22962403
TI  - Missed sclera buckle as a cause of recurrent conjunctivitis.
AB  - A 63-year-old woman was referred to the eye clinic with a 2-year history of
      unresolving right eye discomfort, irritation and recurrent conjunctivitis,
      managed by her general practitioner, where frequent use of topical antibiotics
      and ocular lubricants provided little and transient relief. The right eye was
      blind following a complicated retinal detachment surgery 30 years ago.
      Examination revealed an extruding silicone sponge scleral buckle from a previous
      retinal detachment surgery in the superior conjunctival fornix, under the right
      upper lid. This was subsequently surgically removed and her symptoms resolved.

PMID- 22962405
TI  - Biomarkers for screening, diagnosis, and monitoring of ovarian cancer.
AB  - Serum tumor markers have a major role in the screening, diagnosis, and monitoring
      of most of the gynecologic cancers. Ovarian cancer is one of the deadliest of the
      group because it is so frequently asymptomatic until it has advanced to an
      untreatable stage. Even serum cancer antigen-125 (CA-125), clinically one of the
      most reliable serum markers for ovarian cancer, is elevated in only half of early
      stage still-treatable tumors. Because of the very low prevalence of ovarian
      cancer in the general population, at present, there is no cost-effective imaging
      or simple microscopic screening test for ovarian cancer as there is for breast
      and cervical cancers. However, recent proteomics and nucleic acid-based analyses
      have shown great promise for the discovery of new and more useful serum
      biomarkers, which cumulatively might provide such a screening tool. In this
      review, we will discuss both the currently used serum tumor markers for
      screening, diagnosis, monitoring of ovarian cancer, and the novel biomarkers that
      are now under investigation and validation.

PMID- 22962404
TI  - A variable age of onset segregation model for linkage analysis, with correction
      for ascertainment, applied to glioma.
AB  - BACKGROUND: We propose a 2-step model-based approach, with correction for
      ascertainment, to linkage analysis of a binary trait with variable age of onset
      and apply it to a set of multiplex pedigrees segregating for adult glioma.
      METHODS: First, we fit segregation models by formulating the likelihood for a
      person to have a bivariate phenotype, affection status and age of onset, along
      with other covariates, and from these we estimate population trait allele
      frequencies and penetrance parameters as a function of age (N = 281 multiplex
      glioma pedigrees). Second, the best fitting models are used as trait models in
      multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To
      correct for ascertainment, a prevalence constraint is used in the likelihood of
      the segregation models for all 281 pedigrees. Then the trait allele frequencies
      are reestimated for the pedigree founders of the subset of 74 pedigrees chosen
      for linkage analysis. RESULTS: Using the best-fitting segregation models in model
      based multipoint linkage analysis, we identified 2 separate peaks on chromosome
      17; the first agreed with a region identified by Shete and colleagues who used
      model-free affected-only linkage analysis, but with a narrowed peak: and the
      second agreed with a second region they found but had a larger maximum log of the
      odds (LOD). CONCLUSIONS: Our approach was able to narrow the linkage peak
      previously published for glioma. IMPACT: We provide a practical solution to model
      based linkage analysis for disease affection status with variable age of onset
      for the kinds of pedigree data often collected for linkage analysis.

PMID- 22962406
TI  - Interpretation of single and serial measures of HE4 and CA125 in asymptomatic
      women at high risk for ovarian cancer.
AB  - BACKGROUND: Human epididymis protein 4 (HE4) is approved for clinical use with
      CA125 to predict epithelial ovarian cancer in women with a pelvic mass or in
      remission after chemotherapy. Previously reported reference ranges for HE4 are
      inconsistent. METHODS: We report positivity thresholds yielding 90%, 95%, 98%,
      and 99% specificity for age-defined populations of healthy women for HE4, CA125,
      and Risk of Ovarian Malignancy Algorithm (ROMA), a weighted average of HE4 and
      CA125. HE4 and CA125 were measured in 1,780 samples from 778 healthy women aged
      >25 years with a documented deleterious mutation, or aged >35 years with a
      significant family history. Effects on marker levels of a woman's age, ethnicity,
      and epidemiologic characteristics were estimated, as were the population-specific
      means, variances, and within- and between-woman variances used to generate
      longitudinal screening algorithms for these markers. RESULTS: CA125 levels were
      lower with Black ethnicity (P = 0.008). Smoking was associated with higher HE4 (P
      = 0.007) and ROMA (P < 0.019). Continuous oral contraceptive use decreased levels
      of CA125 (P = 0.041), and ROMA (P = 0.12). CA125 was lower in women age >=55, and
      HE4 increased with age (P < 0.01), particularly among women age >=55.
      CONCLUSIONS: Because of the strong effect of age on HE4, thresholds for HE4 are
      best defined for women of specific ages. Age-specific population thresholds for
      HE4 for 95% specificity ranged from 41.4 pmol/L for women age 30 to 82.1 pmol/L
      for women age 80. IMPACT: Incorporation of serial marker values from screening
      history reduces personalized thresholds for CA125 and HE4 but is inappropriate
      for ROMA.

PMID- 22962407
TI  - Time to get serious about skin cancer prevention.
AB  - In this commentary, we discuss the skin cancer epidemic in the United States and
      provide data to indicate that the United States public is not protecting itself
      from ultraviolet radiation, the primary risk factor for melanoma, and nonmelanoma
      skin cancer. In our opinion, skin cancer control in this country may be hindered
      by uncertainty about the effectiveness of sun protection strategies, inconsistent
      messages about the relative effectiveness of sun protection measures by federal
      and national organizations, and conventional research approaches that have
      identified few effective sun protection interventions for adults and targeted
      individuals for behavior change without considering the environmental context. A
      policy and research agenda is put forth to remedy the apparent insufficiencies in
      the current approach to skin cancer prevention in the United States.

PMID- 22962408
TI  - P-cresol, but not p-cresylsulphate, disrupts endothelial progenitor cell function
      in vitro.
AB  - BACKGROUND: Patients afflicted with chronic kidney disease (CKD) typically suffer
      from cardiovascular disease (CVD) which is a leading cause of patient mortality.
      It has been demonstrated that two distinct physiological events contribute to
      this disease state. These include the abundance of abnormally high levels of
      protein-bound uraemic toxins as well as functionally aberrant endothelial
      progenitor cells (EPCs). Specifically, it has been demonstrated that the uraemic
      toxin p-cresol (pC; 4-methylphenol) inhibits EPC proliferation and tube formation
      in previous in vitro studies. More recently, however, it has been demonstrated
      that circulating pC is actually conjugated and that p-cresylsulphate (pCS) is its
      main metabolite. Therefore, within the context of this study, we examined the in
      vitro effects of pC and pCS treatment on cultured human EPCs. METHODS: Late
      outgrowth EPCs were treated with physiological concentrations of pC or pCS (10,
      40, 80, and 160 or 10, 40, 80, 160 and 320 ug/mL for up to 72 h, respectively) in
      the presence of 4% human serum albumin (HSA). Cell proliferation was determined
      using WST-1 assay, while migration and tube formation assays were used to
      evaluate EPC function in vitro. Cell cycle analyses were also performed to
      determine the effects of pC and pCS on cell cycle status. RESULTS: With regard to
      EPC proliferation, data demonstrate that pC in the presence or absence of HSA had
      an IC50 of 80.1 and 100.8 ug/mL 72 h post-treatment, respectively, while pCS
      treated groups did not impair EPC proliferation. Similarly, pC-treated groups
      showed limited vessel formation and migration compared with controls and no
      detrimental effects were seen with pCS treatment. Lastly, pC treatment of EPCs
      caused cells to accumulate in the G2/M phase of the cell cycle with accompanied
      down-regulation of cyclin B1 and phosphorylated CDK1. pCS had no effect on cell
      cycle parameters. CONCLUSIONS: Our data demonstrate that pC and pCS have
      different effects on EPC function. Since there is a dearth of data that have
      focused on the toxicity of pCS, further research should be performed to determine
      the exact biological toxicity of pCS on the cardiovascular system.

PMID- 22962409
TI  - Blood pressure variability and outcomes in chronic kidney disease.
AB  - BACKGROUND: We investigated the effects of visit-to-visit systolic blood pressure
      variability (SBPV) on both mortality and dialysis inception in a cohort of
      chronic kidney disease (CKD) patients not requiring dialysis therapy.
      Furthermore, we also explored the carry-over effect of visit-to-visit SBPV on
      mortality after dialysis initiation. METHODS: We conducted a longitudinal
      retrospective, observational, multi-centre study in three tertiary care
      nephrology outpatient clinics. All the ambulatory CKD patients admitted to the
      outpatient clinics from 1 January 2004 to 31 December 2005 were screened for
      study eligibility. We selected all consecutive patients older than 18 years of
      age with a mean estimated glomerular filtration rate of <60 mL/min/m(2), free
      from cardiovascular disease. SBPV was defined as the ratio of the SD to the mean
      SBP of five values recorded during a run-in phase of 4-5 months. Data on dialysis
      inception and mortality were recorded through 31 December 2010. RESULTS: Overall,
      we selected a cohort of 374 elderly (median age: 79 years) subjects. A total of
      232 (62%) and 103 (29%) patients were male and had diabetes, respectively. A
      significant association between SBPV and the risk of death but not of CKD
      progression to dialysis was noted at univariate and after multivariable
      adjustments (hazard ratio for all-cause mortality per 1% increase in SBPV: 1.05;
      95% confidence interval: 1.02-1.09; P = 0.001). Notably, no lethal event was
      recorded after dialysis initiation. CONCLUSIONS: Current findings suggest that
      SBPV may be of use for risk stratification in CKD patients.

PMID- 22962410
TI  - Optimizing AVF creation prior to dialysis start: the role of predialysis renal
      replacement therapy choices.
AB  - BACKGROUND: In British Columbia, multidisciplinary predialysis clinics encourage
      patients to consider independent modalities of renal replacement therapy (RRT)
      such as peritoneal dialysis (PD) 'first'. Despite up to 50% of patients choosing
      PD, PD incidence rates are ~30%. We explored the relationship between predialysis
      RRT choice and arteriovenous fistula (AVF) creation prior to hemodialysis (HD)
      start with particular focus on the group of patients who despite PD choice
      actually commence HD, and thus may contribute to 'suboptimal' HD starts without
      AVF creation. METHODS: We conducted a retrospective cohort study of all patients
      starting dialysis between 31 December, 2006 and 31 December 2008 in the province
      of British Columbia. Inclusion criteria were >3 months predialysis nephrology
      follow-up, at least one predialysis RRT education session and maintenance on
      dialysis for a minimum of 3 months (to ensure chronic dialysis). Patients with
      any prior history of RRT were excluded. RESULTS: There were 508 patients included
      in the study: 127 (25%) patients chose HD, 114 (22%) PD, 13 (3%) pre-emptive
      transplant, 5 (1%) conservative management and 249 (49%) had no documented
      modality decision. Of those who chose HD, 94% commenced HD. For those who chose
      PD, 64% commenced PD and 36% HD. In the undecided group, 68% started HD and 32%
      PD. For those patients who chose PD predialysis, the presence of cardiovascular
      disease [odds ratio (OR) 2.36, 95% confidence interval (CI) 1.02-5.43] and lower
      serum albumin levels (OR 0.92, 95% CI 0.86-0.98) were associated with failure to
      commence PD. Predialysis AVF creation rates were 79% of those who chose and
      started HD, 39% of those who chose PD but started HD and 50% of those in the
      undecided group who commenced HD. CONCLUSIONS: AVF creation rates prior to HD
      start were lower in those patients with no documented dialysis modality choice
      and in those who failed to commence PD. Cardiovascular disease and lower serum
      albumin levels were associated with failure to start PD. Further work to ensure
      the efficacy of RRT modality choice pathway and to better predict those patients
      who will fail to commence PD is necessary, so that dialysis start can be
      'optimized' with AVF creation in high-risk groups.

PMID- 22962411
TI  - A randomized controlled trial of oral heme iron polypeptide versus oral iron
      supplementation for the treatment of anaemia in peritoneal dialysis patients:
      HEMATOCRIT trial.
AB  - BACKGROUND: Preliminary clinical evidence suggests that heme iron polypeptide
      (HIP) might represent a promising, novel oral iron supplementation strategy in
      chronic kidney disease. The aim of this multi-centre randomized controlled trial
      was to determine the ability of HIP administration to augment iron stores in
      darbepoetin (DPO)-treated patients compared with conventional oral iron
      supplementation. METHODS: Adult peritoneal dialysis (PD) patients treated with
      DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous
      sulphate per os for 6 months. The primary outcome measure was transferrin
      saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO
      dose and responsiveness, and adverse events. RESULTS: Sixty-two patients were
      randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat
      analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group
      compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not
      significantly associated with TSAT at 6 months on multivariable analysis (P =
      0.95). Similar results were found on per-protocol analysis and subgroup analysis
      in iron-deficient patients. Serum ferritin levels at 6 months were significantly
      lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than
      that of ferrous sulphate. No other differences in secondary outcomes were
      observed. CONCLUSIONS: HIP showed no clear safety or efficacy benefit in PD
      patients compared with conventional oral iron supplements. The reduction in serum
      ferritin levels and high costs associated with HIP therapy suggest that this
      agent is unlikely to have a significant role in iron supplementation in PD
      patients.

PMID- 22962412
TI  - The vulnerable man: impact of testosterone deficiency on the uraemic phenotype.
AB  - Testosterone deficiency or hypogonadism is a common finding in men undergoing
      dialysis, to a great extent a consequence of the failing kidney per se.
      Testosterone restoration in hypogonadism is common practice among
      endocrinologists. However, there is currently little awareness of this condition
      among both uremic patients and nephrologists, and in many cases, testosterone
      deficiency remains unscreened and untreated. This review article summarizes our
      current understanding of the role of testosterone deficiency at the crossroad of
      cardiometabolic complications of patients with chronic kidney disease. Pathways
      discussed include, among others, the plausible role of testosterone deficiency in
      the development of anaemia and ESA hyporesponsiveness, muscle catabolism,
      endothelial dysfunction, cognitive dysfunction, decreased libido, cardiovascular
      disease and mortality. As there are limited sources to guide decision-making, we
      also review existing testosterone replacement therapy studies in the context of
      CKD as well as considerations for side and adverse effects. This review makes a
      case for consideration of screening and better management of hypogonadism in men
      undergoing dialysis.

PMID- 22962413
TI  - Alpha-secretase inhibition reduces human glioblastoma stem cell growth in vitro
      and in vivo by inhibiting Notch.
AB  - The Notch pathway is dysregulated and a potential target in glioblastoma
      multiforme (GBM). Currently available Notch inhibitors block gamma-secretase,
      which is necessary for Notch processing. However, Notch is first cleaved by alpha
      secretase outside the plasma membrane, via a disintegrin and metalloproteinase-10
      and -17. In this work, we used a potent alpha-secretase inhibitor (ASI) to test
      inhibition of glioblastoma growth and inhibition of Notch and of both novel and
      known Notch targets. Featured in this study are luciferase reporter assays and
      immunoblot, microarray analysis, chromatin immunoprecipitation (ChIP),
      quantitative real-time PCR, cell number assay, bromodeoxyuridine incorporation,
      plasmid rescue, orthotopic xenograft model, and local delivery of treatment with
      convection-enhanced delivery using nanoparticles, as well as survival, MRI, and
      ex vivo luciferase assay. A CBF1-luciferase reporter assay as well as an
      immunoblot of endogenous Notch revealed Notch inhibition by the ASI. Microarray
      analysis, quantitative real-time PCR, and ChIP of ASI and gamma-secretase
      inhibitor (GSI) treatment of GBM cells identified known Notch pathway targets, as
      well as novel Notch targets, including YKL-40 and leukemia inhibitory factor.
      Finally, we found that local nanoparticle delivery of ASIs but not GSIs increased
      survival time significantly in a GBM stem cell xenograft treatment model, and ASI
      treatment resulted in decreased tumor size and Notch activity. This work
      indicates alpha-secretase as an alternative to gamma-secretase for inhibition of
      Notch in GBM and possibly other cancers as well, and it identifies novel Notch
      targets with biologic relevance and potential as biomarkers.

PMID- 22962414
TI  - A thromboembolic model for the efficacy and safety evaluation of combined
      mechanical and pharmacologic revascularization strategies.
AB  - BACKGROUND AND PURPOSE: Recanalization strategies mediated by intra-arterial
      fibrinolytic therapy in combination with mechanical clot disruption may be a more
      effective treatment approach than either therapy used alone. There are few
      preclinical animal models to evaluate these strategies. Here we report on a model
      to simultaneously evaluate both of these treatment approaches. METHODS:
      Allogeneic clot was injected through the 6 F guide catheter after creating >50%
      luminal stenosis of the common carotid arteries of New Zealand White rabbits. The
      stenosis was released after 1 h, allowing sufficient time for clot-vessel wall
      interaction. Occlusion was confirmed and each vessel was assigned to receive
      either balloon angioplasty alone, intra-arterial tissue plasminogen activator
      (tPA, Alteplase, Genentech, San Francisco, California, USA), tPA delivery through
      prototype balloon infusion wire (NIT Therapeutics, Pittsburgh, Pennsylvania,
      USA), partial stent deployment or partial stent deployment with locally delivered
      tPA. The negative control received no treatment. RESULTS: In vivo
      revascularization Thrombolysis in Cerebral Infarction (TICI) score revealed that
      the balloon infusion wire achieved a stable and higher revascularization score of
      TICI 2B, with a lower dose of tPA in comparison with other treatment strategies.
      All treatment strategies resulted in endothelial denudation and exposure of the
      internal elastic lamina. CONCLUSIONS: The proposed animal model permits reliable
      and consistent thromboembolic occlusion of the target vasculature and allows for
      an assessment of both pharmacologic and mechanical revascularization strategies
      for acute ischemic stroke.

PMID- 22962417
TI  - Psychosocial characteristics associated with frequent physical fighting: findings
      from the 2009 National Youth Risk Behavior Survey.
AB  - The goal of the current study was to determine the prevalence and psychosocial
      correlates associated with frequent fighting among US high school students. Cross
      sectional analyses were conducted using the 2009 Youth Risk Behavior Survey (N=16
      410). Multivariate logistic regression analyses determined associations between
      demographic and psychosocial correlates of frequent fighting. Among students,
      13.6% reported fighting once, 15.3% reported fighting 2-11 times and 2.6%
      reported fighting 12 or more times in the past year. Risk factors associated with
      frequent fighting were weapon carrying (adjusted OR=10.55; 95% CI 7.40 to 15.05),
      suicide attempt (adjusted OR=6.16; 95% CI 3.70 to 10.28), binge drinking
      (adjusted OR=3.15; 95% CI 2.16 to 4.59) and feeling too unsafe to go to school
      (adjusted OR=3.09; 95% CI 2.00 to 4.77). There is a clear need to better
      understand the patterns and psychosocial characteristics of frequent physical
      fighting and the prevention and interventions strategies that may be most
      relevant for these vulnerable youth.

PMID- 22962419
TI  - Pop quiz. A 47-year-old man with chronic tongue pain.

PMID- 22962420
TI  - Maximal electric separation-guided placement of right ventricular lead improves
      responders in cardiac resynchronization defibrillator therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy is widely used for the treatment of
      heart failure. Recent data suggest that electric separation during left
      ventricular pacing varies within the right ventricle (RV). We hypothesized that
      placement of the RV lead guided by maximal electric separation (MES) would
      improve response to cardiac resynchronization therapy compared with standard
      apical placement. METHODS AND RESULTS: A single-blind, randomized controlled
      trial was conducted. Patients eligible for cardiac resynchronization therapy-D
      were enrolled. Left ventricular lead placement was performed at the coronary
      sinus branch. The RV outflow tract, septum, and apex were mapped during left
      ventricular pacing and MES recorded. Patients were randomized to receive either
      apical placement or RV lead placement at the site mapping MES. Left ventricular
      ejection fraction, 6-minute walk distance, and New York Heart Association
      functional class were recorded at baseline and 3 months by blinded observers.
      Response was defined as at least one of the following: 5% absolute increase in
      ejection fraction, 50 m increase in 6-minute walk distance, or an increase by >1
      functional class. Primary end point was improvement in ejection fraction at 3
      months. Fifty patients were randomized (25 MES-guided and 25 apical). Baseline
      characteristics were similar in the 2 groups. Electric separation was lower in
      the apex (143 +/- 23 versus 168 +/- 25 ms in MES group; P=0.01). MES was most
      commonly septal and rarely apical (4/50 patients). Responders in the MES-guided
      versus apical group are as follows: Echo 21 versus 13 patients (P=0.032), 6
      minute walk distance 19 versus 12 patients (P=0.079), and functional class 22
      versus 15 patients (P=0.051). No dislodgment or reposition for suboptimal
      defibrillation tests was reported. CONCLUSIONS: MES-guided placement of the RV
      lead improves cardiac resynchronization therapy responders compared with standard
      apical placement.

PMID- 22962421
TI  - Efficacy and safety of orbital radiotherapy for graves' orbitopathy.
AB  - CONTEXT: Graves' orbitopathy (GO), when moderate-to-severe and active, requires
      medical treatment. High-dose glucocorticoids (GCs) represent the first-line
      treatment. Orbital radiotherapy (OR) has been used for decades, alone or in
      combination with GCs, but opinions on its efficacy are conflicting. EVIDENCE
      ACQUISITION: The major source of data acquisition included PubMed strategies.
      Original articles, systemic reviews and metaanalyses, and other relevant
      citations were screened. EVIDENCE SYNTHESIS: Randomized clinical trials
      evaluating the efficacy of OR are limited. However, available data suggest that
      OR is a safe treatment, which seems to be effective particularly on ocular
      motility impairment, especially if it is of recent onset. OR seems to be
      effective also on soft tissue changes, whereas exophthalmos and long-standing
      extraocular muscle dysfunction are poorly affected. OR efficacy on dysthyroid
      optic neuropathy is uncertain. The combination of OR and oral GCs is more
      effective than either treatment alone, suggesting a synergistic effect of the two
      treatments. There is no available evidence that the addition of OR to iv GCs
      provides an advantage over iv GCs alone. CONCLUSIONS: OR can be considered a safe
      second-line treatment for patients with moderate-to-severe and active GO but less
      effective than GCs. A possible strategy may include its use in combination with
      iv GCs in patients whose GO has only partially responded to a first-course of iv
      GCs alone and is still active. Future studies might address the question of
      whether the combination of iv GCs and OR might represent the first-line treatment
      for active GO.

PMID- 22962423
TI  - Predictors of change in serum TSH after iodine fortification: an 11-year follow
      up to the DanThyr study.
AB  - CONTEXT: Few data are available on the effect of iodine fortification on thyroid
      function development in a population. OBJECTIVE: Our objective was to evaluate
      changes in thyroid function after iodine fortification in a population and to
      identify predictors for changes in serum TSH. DESIGN AND SETTING: A longitudinal
      population-based study of the DanThyr C1 cohort examined at baseline (1997-1998)
      and reexamined 11 yr later (2008-2010). The mandatory program for iodization of
      salt was initiated in 2000. PARTICIPANTS: A total of 2203 individuals, with no
      previous thyroid disease, living in two areas with different levels of iodine
      intake, with measurement of TSH and participation in follow-up examination were
      included in the analysis. MAIN OUTCOME MEASURE: Change in serum TSH was
      evaluated. RESULTS: During the 11-yr follow-up, mean TSH increased significantly
      from 1.27 mU/liter [95% confidence interval (CI) = 1.23-1.30] to 1.38 mU/liter
      (CI = 1.34-1.43) (P < 0.001). The most pronounced increase was observed in the
      area with the highest iodine intake [1.30 mU/liter (CI = 1.25-1.35) to 1.49
      mU/liter (CI = 1.43-1.55), P < 0.001], whereas the increase was not significant
      in the low-iodine-intake area [1.24 (CI = 1.19-1.29) to 1.28 (CI = 1.23-1.34), P
      = 0.06)]. Change in TSH was positively associated with the presence of thyroid
      peroxidase antibody at baseline (P < 0.001) and negatively associated with
      baseline thyroid enlargement (P < 0.001) and multiple nodules (P < 0.001).
      CONCLUSIONS: Even small differences in the level of iodine intake between
      otherwise comparable populations are associated with considerable differences in
      TSH change at the 11-yr follow-up. Multinodular goiter predicted a less
      pronounced TSH increase during follow-up, which may be explained by iodine
      dependent activity of autonomous nodules.

PMID- 22962422
TI  - PTEN lipid phosphatase activity and proper subcellular localization are necessary
      and sufficient for down-regulating AKT phosphorylation in the nucleus in Cowden
      syndrome.
AB  - CONTEXT: Germline mutations in PTEN are associated with phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN) hamartoma tumor syndrome including Cowden
      syndrome (CS) and Cowden-like syndrome (CSL) that predisposes to high risks of
      benign and malignant tumors of thyroid and breast. OBJECTIVE: The objective of
      the study was to analyze the subcellular pattern of phosphorylated (P)-AKT
      expression in nonmedullary thyroid cancers from PTEN hamartoma tumor syndrome
      patients and to investigate whether the lack of PTEN in the nucleus and/or lack
      of proper PTEN function in the nucleus affect(s) nuclear AKT activity in CS
      patients. DESIGN: In all, 664 patients with CS/CSL were screened for PTEN
      germline mutations and nonmedullary thyroid cancers. Twenty-two patients who have
      both pathogenic PTEN germline mutations and nonmedullary thyroid cancers were
      selected. Thyroid samples from these patients were stained for PTEN and P-AKT. In
      our in vitro study, PTEN was knocked down or overexpressed in both thyroid cancer
      cells and breast cancer cells, and nuclear P-AKT was compared with the control.
      RESULTS: Loss of PTEN protein was found in thyroid adenomas and carcinomas from
      all 22 (100%) PTEN(Mut+) CS/CSL patients. AKT activation was identified in 17 of
      22 (77.3%) thyroid adenoma/carcinoma specimens, and most patients (63.7%) have
      activated nuclear AKT. Knockdown of PTEN in cells containing wild-type PTEN
      enhanced nuclear P-AKT, whereas expression of wild-type PTEN, but not phosphatase
      dead mutants (C124S or G129E), markedly reduced nuclear P-AKT in PTEN null cells.
      We also showed that in breast cancer but not thyroid cancer cells, PTEN
      suppresses nuclear P-AKT mainly through decreasing P-AKT nuclear translocation by
      reducing the PIP3/P-AKT reservoir in the cytoplasm. In thyroid cancer cells, PTEN
      suppresses phosphorylation of AKT already resident in the nucleus. CONCLUSIONS:
      PTEN is necessary and sufficient for inhibiting AKT activation in the nucleus
      through its intact lipid phosphatase activity and proper subcellular
      localization.

PMID- 22962424
TI  - Malignant pheochromocytoma imaging with [124I]mIBG PET/MR.

PMID- 22962425
TI  - Central QCT reveals lower volumetric BMD and stiffness in premenopausal women
      with idiopathic osteoporosis, regardless of fracture history.
AB  - CONTEXT: Idiopathic osteoporosis (IOP) affects otherwise healthy young
      individuals with intact gonadal function and no secondary cause of bone
      fragility. In premenopausal women with IOP, a low trauma fracture is evidence of
      impaired bone quality and strength. The extent to which low bone mineral density
      (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone
      microstructure, and strength is uncertain in the absence of low trauma fracture.
      OBJECTIVE: The objective of the study was to compare three-dimensional volumetric
      BMD and bone stiffness in premenopausal women with IOP based on fracture history,
      those with idiopathic low BMD (Z score <= -2.0) and no low trauma fracture, and
      normal age-matched controls. DESIGN: We measured volumetric BMD and bone geometry
      by central quantitative computed tomography (cQCT) scans of the spine and hip and
      estimated bone stiffness by finite element analysis of cQCT data sets in 32
      premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls.
      RESULTS: Subjects had comparable decreases in total and trabecular volumetric
      BMD, cortical thickness, and whole-bone stiffness compared with controls,
      regardless of fracture history. These differences remained significant after
      controlling for age, body mass index, and bone size. The positive predictive
      values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0
      or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the
      femoral neck. CONCLUSION: Women with idiopathic low BMD alone and those with low
      trauma fractures had comparable deficits in bone mass, structure, and stiffness.
      Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by
      cQCT. These results are consistent with three-dimensional bone imaging at the
      iliac crest, radius, and tibia in premenopausal IOP and suggest that the term
      osteoporosis may be appropriate in women with Z scores below -2.0, whether or not
      there is a history of fracture.

PMID- 22962426
TI  - Magnesium supplementation does not affect blood calcium level in treated
      hypoparathyroid patients.
AB  - CONTEXT: Magnesium is involved in the homeostasis of calcium metabolism, and
      magnesium deficiency may lead to clinically significant hypocalcemia. We have had
      two cases in our department in which treated hypoparathyroid patients with stable
      calcium levels developed hypercalcemia in conjunction with supplementary
      magnesium use. To our knowledge, there has been no prospective study looking at
      the effect of supplementary magnesium on calcium homeostasis in hypoparathyroid
      patients. OBJECTIVE: The aim of this pilot study was to evaluate whether
      magnesium treatment affects plasma calcium levels in hypoparathyroid patients.
      DESIGN AND SETTING: We conducted a prospective, two-phase, uncontrolled treatment
      trial at a referral center of endocrine disorders. PARTICIPANTS: We enrolled
      treated (calcium + vitamin D analog) hypoparathyroid patients with normal plasma
      magnesium levels. INTERVENTION: Three weeks of treatment with oral magnesium (350
      mg/d) were followed by 2 wk off treatment. MEASURES: We compared the plasma
      ionized calcium level after 3 wk of treatment to the pretreatment value. Plasma
      calcium, phosphate, magnesium, and creatinine levels were measured before
      treatment, after 3 wk on magnesium, and 2 wk after stopping magnesium treatment.
      RESULTS: Ten patients completed the trial. Supplementary treatment with magnesium
      for 3 wk did not change calcium levels in these patients. Magnesium
      supplementation induced a small but statistically significant increase in the
      plasma magnesium level, but levels of phosphate and creatinine remained stable.
      CONCLUSIONS: Magnesium supplementation did not influence plasma calcium levels in
      treated hypoparathyroid patients.

PMID- 22962427
TI  - Effect of continuous positive airway pressure therapy on cardiovascular risk
      factors in patients with type 2 diabetes and obstructive sleep apnea.
AB  - CONTEXT: Few prospective intervention studies have examined the effect of
      continuous positive airway pressure (CPAP) therapy on cardiovascular disease
      (CVD) risk factors in diabetes. OBJECTIVE: Our objective was to determine whether
      CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive
      sleep apnea (OSA). DESIGN AND SETTING: This was a randomized parallel group
      intervention trial in an urban Australian community. PATIENTS: Fifty-nine
      participants of the Fremantle Diabetes Study Phase II at high risk for OSA
      consented to confirmatory polysomnography followed by randomization to a 3-month
      CPAP intervention initiated early (<1 wk) or late (1-2 months). MAIN OUTCOME
      MEASURES: Patients were assessed before and 1 and 3 months after CPAP started.
      Tests for repeated measures were used to compare variables of interest over time.
      RESULTS: Forty-four patients (75%) completed the study. Their mean +/- sd age was
      66.1 +/- 8.8 yr, and 61.4% were male. Completers and noncompleters had similar
      age, sex, diabetes duration, apnea-hypopnea index, and Epworth Sleepiness Scale
      (P >= 0.29). There were no differences in outcome between early and late
      randomization, and the data were pooled. The Epworth Sleepiness Scale decreased
      between entry and 1 month [-4.8 (-6.5 to -3.1), P < 0.001]. Blood pressure
      improved between entry and 3 months (from 149 +/- 23/80 +/- 12 to 140 +/- 18/73
      +/- 13 mm Hg; P <= 0.007). Pulse rate declined within the first month [-6 (-10 to
      -2) beats/min, P = 0.002]. Glycemic control and serum lipids, which were mostly
      within recommended target ranges at entry, did not change. CONCLUSIONS: Three
      months of CPAP in community-based people with type 2 diabetes significantly
      decreased blood pressure and pulse rate but did not influence metabolic control.

PMID- 22962428
TI  - The effect of a short sprint on postexercise whole-body glucose production and
      utilization rates in individuals with type 1 diabetes mellitus.
AB  - CONTEXT: Recently we showed that a 10-sec maximal sprint effort performed before
      or after moderate intensity exercise can prevent early hypoglycemia during
      recovery in individuals with type 1 diabetes mellitus (T1DM). However, the
      mechanisms underlying this protective effect of sprinting are still unknown.
      OBJECTIVE: The objective of the study was to test the hypothesis that short
      duration sprinting increases blood glucose levels via a disproportionate increase
      in glucose rate of appearance (Ra) relative to glucose rate of disappearance
      (Rd). SUBJECTS AND EXPERIMENTAL DESIGN: Eight T1DM participants were subjected to
      a euglycemic-euinsulinemic clamp and, together with nondiabetic participants,
      were infused with [6,6-(2)H]glucose before sprinting for 10 sec and allowed to
      recover for 2 h. RESULTS: In response to sprinting, blood glucose levels
      increased by 1.2 +/- 0.2 mmol/liter (P < 0.05) within 30 min of recovery in T1DM
      participants and remained stable afterward, whereas glycemia rose by only 0.40 +/
      0.05 mmol/liter in the nondiabetic group. During recovery, glucose Ra did not
      change in both groups (P > 0.05), but glucose Rd in the nondiabetic and diabetic
      participants fell rapidly after exercise before returning within 30 min to
      preexercise levels. After sprinting, the levels of plasma epinephrine,
      norepinephrine, and GH rose transiently in both experimental groups (P < 0.05).
      CONCLUSION: A sprint as short as 10 sec can increase plasma glucose levels in
      nondiabetic and T1DM individuals, with this rise resulting from a transient
      decline in glucose Rd rather than from a disproportionate rise in glucose Ra
      relative to glucose Rd as reported with intense aerobic exercise.

PMID- 22962429
TI  - C-Type Natriuretic Peptide (CNP) levels are altered in boys with Klinefelter
      syndrome.
AB  - CONTEXT: B-type natriuretic peptide (BNP) expression in vitro is up-regulated by
      the protein coded by the short stature homeobox gene (SHOX). C-type natriuretic
      peptide (CNP) is a paracrine regulatory factor of the growth plate that plays a
      key role in endochondral growth and shares clearance pathways with BNP. We
      explored the possibility that alterations in natriuretic peptide regulation may
      play a role in the overgrowth of boys with Klinefelter syndrome. OBJECTIVE: The
      objectives of the study were to document the blood levels of amino-terminal
      propeptide of B-type natriuretic peptide (NTproBNP), CNP, and its amino-terminal
      propeptide (NTproCNP) in boys with Klinefelter syndrome and compare values with
      age- and height-matched control subjects. DESIGN: This was a prospective, case
      controlled, observational study. SUBJECTS: Participants were 24 healthy boys with
      Klinefelter syndrome between 4 and 14 yr of age. Data from sex-, age-, and height
      matched healthy controls were obtained from subjects participating in a
      previously described study. RESULTS: Plasma levels of NTproBNP and CNP were
      lower, whereas levels of NTproCNP were higher in boys with Klinefelter syndrome
      compared with published reference ranges. In addition, CNP levels were lower and
      NTproCNP levels higher than in sex-, age-, and height-matched controls.
      CONCLUSIONS: In contrast to plasma NTproBNP, CNP production and clearance are
      increased in boys with Klinefelter syndrome. Together these findings argue
      against an interaction between BNP with CNP in the growth plate. Why CNP peptide
      levels are altered in Klinefelter syndrome remains to be explored.

PMID- 22962430
TI  - Severely fluctuating blood glucose levels associated with a somatostatin
      producing ovarian neuroendocrine tumor.
AB  - CONTEXT: Somatostatin-producing tumors are a rare type of neuroendocrine tumor.
      Their effects on blood glucose levels have been variously reported, and detailed
      reports have been scarce. OBJECTIVE: The aim of this study was to identify the
      reasons for the extraordinary blood glucose fluctuations in a case with no
      previous history of diabetes. PATIENTS AND METHODS: A 68-yr-old nondiabetic woman
      with an ovarian tumor was suffering from hyper- and hypoglycemia. Based on the
      results of an oral glucose tolerance test and continuous glucose monitoring, we
      speculated that the fluctuating blood glucose level was accompanied not only by a
      low insulin level but also by low counter-regulatory hormones levels, and that
      those broad hormonal suppressions were caused by a high somatostatin level
      produced in the ovarian tumor. We performed an oophorectomy and assessed the
      pathology of the tumor and changes in the blood glucose profile as well as
      hormonal levels postoperatively. RESULTS: The blood glucose level was completely
      normalized after the oophorectomy. Insulin secretion was also normalized.
      Histological examination showed that the tumor comprised a mature cystic teratoma
      and a stromal carcinoid. Immunohistochemically, the stromal carcinoid component
      was positive for somatostatin. The somatostatin level was 8505 pmol/liter
      preoperatively, which dropped down to 71.5 pmol/liter postoperatively. We found
      two previous reports of somatostatin-producing ovarian neuroendocrine tumors.
      Somatostatin levels among cases of ovarian origin were much higher than those
      among cases of gastrointestinal origins, and cases of ovarian origin all
      experienced blood glucose fluctuations. CONCLUSION: Extremely high somatostatin
      levels and blood glucose fluctuations may be characteristics of somatostatin
      producing ovarian neuroendocrine tumors.

PMID- 22962431
TI  - The study of antiarrhythmic medications in infancy (SAMIS): a multicenter,
      randomized controlled trial comparing the efficacy and safety of digoxin versus
      propranolol for prophylaxis of supraventricular tachycardia in infants.
AB  - BACKGROUND: Supraventricular tachycardia (SVT) is one of the most common
      conditions requiring emergent cardiac care in children, yet its management has
      never been subjected to a randomized controlled clinical trial. The purpose of
      this study was to compare the efficacy and safety of the 2 most commonly used
      medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and
      propranolol. METHODS AND RESULTS: This was a randomized, double-blind,
      multicenter study of infants <4 months with SVT (atrioventricular reciprocating
      tachycardia or atrioventricular nodal reentrant tachycardia), excluding Wolff
      Parkinson-White, comparing digoxin with propranolol. The primary end point was
      recurrence of SVT requiring medical intervention. Time to recurrence and adverse
      events were secondary outcomes. Sixty-one patients completed the study, 27
      randomized to digoxin and 34 to propranolol. SVT recurred in 19% of patients on
      digoxin and 31% of patients on propranolol (P=0.25). No first recurrence occurred
      after 110 days of treatment. The 6-month recurrence-free status was 79% for
      patients on digoxin and 67% for patients on propranolol (P=0.34), and there were
      no first recurrences in either group between 6 and 12 months. There were no
      deaths and no serious adverse events related to study medication. CONCLUSIONS:
      There was no difference in SVT recurrence in infants treated with digoxin versus
      propranolol. The current standard practice may be treating infants longer than
      required and indicates the need for a placebo-controlled trial. Clinical Trial
      Registration Information- http://clinicaltrials.gov; NCT-00390546.

PMID- 22962432
TI  - PPARgamma regulates resistance vessel tone through a mechanism involving RGS5
      mediated control of protein kinase C and BKCa channel activity.
AB  - RATIONALE: Activation of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) by thiazolidinediones lowers blood pressure, whereas PPARgamma
      mutations cause hypertension. Previous studies suggest these effects may be
      mediated through the vasculature, but the underlying mechanisms remain unclear.
      OBJECTIVE: To identify PPARgamma mechanisms and transcriptional targets in
      vascular smooth muscle and their role in regulating resistance artery tone.
      METHODS AND RESULTS: We studied mesenteric artery (MA) from transgenic mice
      expressing dominant-negative (DN) mutant PPARgamma driven by a smooth muscle cell
      specific promoter. MA from transgenic mice exhibited a robust increase in
      myogenic tone. Patch clamp analysis revealed a reduced large conductance Ca(2+)
      activated K(+) (BKCa) current in freshly dissociated smooth muscle cell from
      transgenic MA. Inhibition of protein kinase C corrected both enhanced myogenic
      constriction and impaired the large conductance Ca(2+)-activated K(+) channel
      function. Gene expression profiling revealed a marked loss of the regulator of G
      protein signaling 5 (RGS5) mRNA in transgenic MA, which was accompanied by a
      substantial increase in angiotensin II-induced constriction in MA. Small
      interfering RNA targeting RGS5 caused augmented myogenic tone in intact
      mesenteric arteries and increased activation of protein kinase C in smooth muscle
      cell cultures. PPARgamma and PPARdelta each bind to a PPAR response element close
      to the RGS5 promoter. RGS5 expression in nontransgenic MA was induced after
      activation of either PPARgamma or PPARdelta, an effect that was markedly blunted
      by DN PPARgamma. CONCLUSIONS: We conclude that RGS5 in smooth muscle is a
      PPARgamma and PPARdelta target, which when activated blunts angiotensin II
      mediated activation of protein kinase C, and preserves the large conductance
      Ca(2+)-activated K(+) channel activity, thus providing tight control of myogenic
      tone in the microcirculation.

PMID- 22962433
TI  - Trends in blood pressure and hypertension detection, treatment, and control 1980
      to 2009: the Minnesota Heart Survey.
AB  - BACKGROUND: Hypertension is common and treatable, but detection and control
      remain a major health challenge. This study sought to determine population trends
      in blood pressure and in the control of hypertension in the Minneapolis/St. Paul
      area (2010 population, 2.85 million) from 1980 to 2009. METHODS AND RESULTS:
      Surveys of risk factors were performed every 5 years among randomly selected
      adults aged 25 to 74 years. Data on hypertension knowledge and use of medications
      were collected by interview. Blood pressure was measured by standardized methods,
      with hypertension defined as blood pressure >=140 mm Hg systolic and/or 90 mm Hg
      diastolic or controlled at <140 and/or 90 mm Hg with medications. Six surveys
      included 11 192 men and 12 795 women. Mean systolic blood pressure fell from
      124.9 mm Hg in 1980 to 1982 to 121.1 mm Hg in 2007 to 2009 for men (P<0.0001) and
      from 120.1 to 114.7 mm Hg for women (P<0.0001). Similar trends for diastolic
      blood pressure were observed. The percentage of adults with uncontrolled blood
      pressure (>=140 and/or 90 mm Hg) with or without medication use fell from 20.3%
      to 5.8% (P<0.001) for men and from 13.1% to 2.7% (P<0.0001) for women.
      Antihypertensive medication use rose to >50% among all adults aged 55 to 74
      years. Sixty-six percent of men and 72% of women with hypertension had their
      hypertension treated or controlled by 2007 to 2009. A majority of the decline in
      mean population blood pressure was the result of control with aggressive use of
      antihypertensive drugs. Stroke mortality in this population fell in parallel.
      CONCLUSIONS: The rate of hypertension detection and control in this community is
      among the highest observed in a US population and already exceeds Healthy People
      2020 goals.

PMID- 22962434
TI  - Identification of human NK cells that are deficient for signaling adaptor
      FcRgamma and specialized for antibody-dependent immune functions.
AB  - NK cells respond to tumor and virus-infected cells directly through several
      activation receptors, including natural cytotoxicity receptors, or indirectly
      through the activating Fc receptor CD16 for antibody-coated cells. Triggering of
      NK-cell effector functions through these receptors depends on physically
      associated transmembrane signaling adaptors, such as FcRgamma (also known as
      FcepsilonRIgamma) and CD3zeta, both of which have been traditionally believed to
      be expressed by all mature NK cells. However, we have identified a distinct
      subset of human NK cells that are deficient for FcRgamma expression but express
      normal levels of CD3zeta. FcRgamma-deficient NK cells were readily detectable in
      about one-third of the healthy individuals examined. The deficiency was confined
      to the CD56(dim) population and was due to low FcRgamma mRNA. FcRgamma-deficient
      NK cells displayed dramatically reduced expression of the natural cytotoxicity
      receptors NKp46 and NKp30 but still expressed substantial levels of CD16.
      Compared to FcRgamma-expressing NK cells, FcRgamma-deficient NK cells showed poor
      direct reactivity toward tumor targets as measured by cytokine production and
      degranulation. Unexpectedly, however, FcRgamma-deficient NK cells exhibited
      significantly more robust responsiveness upon stimulation through CD16,
      particularly for cytokine production, compared to FcRgamma-expressing NK cells.
      Thus, our study reveals FcRgamma-deficient NK cells as a novel subset of human NK
      cells that have remarkably potent responses toward antibody-coated targets. These
      findings also illustrate a differential contribution of FcRgamma and CD3zeta for
      the expression and functional activity of their associated receptors.

PMID- 22962435
TI  - Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to
      a weak ligand monophosphoryl lipid A.
AB  - A cell surface heterodimer Toll-like receptor 4 (TLR4)/MD-2 senses
      lipopolysaccharide (LPS), a principal membrane component of Gram-negative
      bacteria. LPS binds to MD-2 and induces dimerization of TLR4/MD-2. Dimerized TLR4
      activates downstream signaling. TLR4 polymorphism replacing Asp299 with Gly and
      Thr399 with Ile (D299G/T399I) causes LPS hyporesponsiveness, and is associated
      with a variety of infectious and noninfectious diseases. However, a molecular
      mechanism underlying the LPS hyporesponsiveness remains controversial. We here
      asked whether the TLR4 polymorphism influenced cell surface expression of TLR4/MD
      2, ligand-dependent TLR4/MD-2 dimerization or TLR4/MD-2 responses to a weak
      agonist monophosphoryl lipid A (MPL). A newly established anti-TLR4 mAb detected
      D299G/T399I TLR4/MD-2 on Ba/F3 cells, whereas a previous anti-TLR4 mAb did will
      this fit on the line above?, suggesting that the D299G/T399I polymorphism caused
      a conformational change in TLR4. Hyporesponsiveness of D299G/T399I TLR4/MD-2 was
      much more apparent when cells were stimulated with MPL than with lipid A. MPL
      dependent TLR4/MD-2 dimerization was impaired by the D299G/T399I polymorphism.
      The D299G/T399I polymorphism did not alter LPS-binding to soluble TLR4/MD-2, but
      impaired its dimerization. These results suggest that the D299G/T399I TLR4
      polymorphism impairs TLR4/MD-2 responses by altering ligand-dependent
      dimerization.

PMID- 22962436
TI  - Interplay between T(h)1 and T(h)17 effector T-cell pathways in the pathogenesis
      of spontaneous colitis and colon cancer in the Galphai2-deficient mouse.
AB  - Galphai2-deficient mice spontaneously develop colitis. Using xMAP technology and
      RT-PCR, we investigated cytokine/chemokine profiles during histologically defined
      phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without
      dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age
      matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice
      and cancer in 1/11 mice with severe colitis. The histology correlated with
      progressive increases in colon weight/cm and spleen weight, and decreased thymus
      weight, all more advanced in mice with dysplasia/cancer. IL-1beta, IL-6, IL
      12p40, IL-17, TNF-alpha, CCL2 and CXCL1 protein levels in colons, but not small
      intestines increased with colitis progression and were significantly increased in
      mice with moderate and severe colitis compared with WT mice, irrespective of the
      absence/presence of dysplasia/cancer. CCL5 did not change during colitis
      progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages
      of colitis, whereas IFN-gamma mRNA was gradually up-regulated 12- to 55-fold with
      colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27
      mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21
      transcription increased 3-fold in mice with severe colitis, both irrespective of
      the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly
      enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice
      with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis
      demonstrated an association between increased protein levels of TNF-alpha, CCL2,
      IL-1beta, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses
      are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine
      transcription with progression of colitis in Galphai2(-/-) mice.

PMID- 22962437
TI  - Regulation of intestinal homeostasis by innate and adaptive immunity.
AB  - The intestine is a unique tissue where an elaborate balance is maintained between
      tolerance and immune responses against a variety of environmental factors such as
      food and the microflora. In a healthy individual, the microflora stimulates
      innate and adaptive immune systems to maintain gut homeostasis. However, the
      interaction of environmental factors with particular genetic backgrounds can lead
      to dramatic changes in the composition of the microflora (i.e. dysbiosis). Many
      of the specific commensal-bacterial products and the signaling pathways they
      trigger have been characterized. The role of T(h)1, T(h)2 and T(h)17 cells in
      inflammatory bowel disease has been widely investigated, as has the contribution
      of epithelial cells and subsets of dendritic cells and macrophages. To date,
      multiple regulatory cells in adaptive immunity, such as regulatory T cells and
      regulatory B cells, have been shown to maintain gut homeostasis by preventing
      inappropriate innate and adaptive immune responses to commensal bacteria.
      Additionally, regulatory myeloid  cells have recently been identified that
      prevent intestinal inflammation by inhibiting T-cell proliferation. An increasing
      body of evidence has shown that multiple regulatory mechanisms contribute to the
      maintenance of gut homeostasis.

PMID- 22962438
TI  - Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions
      in rheumatoid arthritis patients.
AB  - The involvement of B cells, complement activation and subsequent immune complex
      deposition has all been implicated in the pathogenesis of rheumatoid arthritis
      (RA). Although the reduced expression of complement receptor 1 (CR1, CD35) and 2
      (CR2, CD21) on the B cells of RA patients has been known for a long time, their
      exact role in B-cell tolerance and autoimmunity is not yet fully understood. To
      get a deeper insight into the possible mechanisms, we studied the expression and
      function of CR1 and CR2 on various subsets of B cells of healthy donors and RA
      patients at various stages of the disease by FACS analysis, (3)H-thymidine
      incorporation and ELISA. We found that CD19(+)CD27(-) naive B cells up-regulate
      the expression of the inhibitory CR1 during differentiation to CD19(+)CD27(+)
      memory B cells both in healthy donors and in RA patients, whereas the expression
      of the activatory CR2 is down-regulated. This clearly demonstrates that the
      expression of these two antagonistic complement receptors is regulated
      differentially during the development of human B cells, a phenomenon which may
      influence the maintenance of peripheral B-cell tolerance. Our functional studies
      show that after clustering CR1 both by its natural ligand and To5 mAb, the
      inhibitory function of CD35 is maintained in RA patients, despite its
      significantly reduced expression compared with healthy individuals. Besides
      blocking B-cell receptor-induced proliferation, CR1 inhibits the differentiation
      of B cells to plasmablasts and their immunoglobulin production. Since the reduced
      expression of CR1 in RA patients does not affect its inhibitory function, this
      receptor might serve as a new target for therapeutical interventions.

PMID- 22962439
TI  - Pharmacokinetic and pharmacodynamic analysis of circulating biomarkers of anti
      NRP1, a novel antiangiogenesis agent, in two phase I trials in patients with
      advanced solid tumors.
AB  - PURPOSE: MNRP1685A is a monoclonal antibody to neuropilin-1 (NRP1). We evaluated
      blood-based pharmacodynamic biomarkers of MNRP1685A in two phase I studies to
      assess exposure/response relationships to inform target dose and regimen
      selection. EXPERIMENTAL DESIGN: The phase I studies evaluated escalating doses of
      MNRP1685A as a single agent or in combination with bevacizumab. Plasma placental
      growth factor (PlGF), VEGF, and circulating NRP1 (cNRP1) were evaluated at
      multiple time points using meso-scale discovery (MSD) assays and ELISA,
      respectively. Plasma PlGF was also measured in a phase I/II trial of bevacizumab
      in metastatic breast cancer (AVF0776). The association between PlGF and MNRP1685A
      dose was described by a sigmoid E(max) model. cNRP1 and MNRP1685A PK profiles
      were described using a two-target quasi-steady state (QSS) model. RESULTS: A dose
      and time-dependent increase in plasma PlGF and cNRP1 was observed in all
      patients treated with MNRP1685A. PK/PD analysis showed that bevacizumab and
      MNRP1685A had an additive effect in elevating PlGF. Predictions based on the two
      target QSS model showed that the free drug concentration to maintain greater than
      90% saturation of membrane NRP1 (mNRP1) and cNRP1 is about 8 MUg/mL. CONCLUSION:
      These data show that MNRP1685A inhibits the VEGF pathway in humans as assessed by
      an increase in plasma PlGF. MNRP1685A seems to enhance bevacizumab-mediated VEGF
      pathway blockade, as showed by an increase in the magnitude of PlGF elevation
      when combined with bevacizumab. PK/PD analysis of biomarkers in the phase I
      population allowed identification of doses at which apparent maximal pathway
      modulation was observed.

PMID- 22962440
TI  - A phase I trial and pharmacokinetic study of sorafenib in children with
      refractory solid tumors or leukemias: a Children's Oncology Group Phase I
      Consortium report.
AB  - PURPOSE: To determine the dose-limiting toxicities (DLT), maximum tolerated dose
      (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with
      refractory extracranial solid tumors and evaluate the tolerability of the solid
      tumor MTD in children with refractory leukemias. EXPERIMENTAL DESIGN: Sorafenib
      was administered orally every 12 hours for consecutive 28-day cycles.
      Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted
      during cycle 1. RESULTS: Of 65 patients enrolled, 60 were eligible. In the solid
      tumor cohort (n = 49), 4 of 6 patients experienced a DLT [hypertension, pain,
      rash/urticaria, thrombocytopenia, alanine aminotransferase (ALT)/aspartate
      aminotransferase (AST)] at the starting dose (150 mg/m(2)/dose) which resulted in
      de-escalation to 105 mg/m(2)/dose. After eligibility criteria modification and
      dose re-escalation, the MTD was 200 mg/m(2)/dose for solid tumors and 150
      mg/m(2)/dose for leukemias. Sorafenib exposure was highly variable between
      patients but was within the ranges reported in adults. The apparent sorafenib
      clearance increased with patient age. Diarrhea, rash, fatigue, and increased
      ALT/AST were the most common sorafenib-related toxicities. Stable disease for 4
      or more cycles was observed in 14 solid tumor patients, and 2 patients with acute
      myeloid leukemia (AML) and FLT3 internal tandem duplication (FLT3ITD) experienced
      a decrease in bone marrow blasts to less than 5%. CONCLUSIONS: The recommended
      phase II dose of sorafenib administered every 12 hours continuously for children
      with solid tumors is 200 mg/m(2)/dose and 150 mg/m(2)/dose for children with
      leukemias. Sorafenib toxicities and distribution in children are similar to
      adults. The activity of sorafenib in children with AML and FLT3ITD is currently
      being evaluated, and a phase II study for select solid tumors is ongoing.

PMID- 22962441
TI  - U.S. Food and Drug Administration approval summary: brentuximab vedotin for the
      treatment of relapsed Hodgkin lymphoma or relapsed systemic anaplastic large-cell
      lymphoma.
AB  - The U.S. Food and Drug Administration (FDA) describes the accelerated approval of
      brentuximab vedotin for patients with relapsed Hodgkin lymphoma and relapsed
      systemic anaplastic large-cell lymphoma (sALCL). FDA analyzed the results of two
      single-arm trials, enrolling 102 patients with Hodgkin lymphoma and 58 patients
      with sALCL. Both trials had primary endpoints of objective response rate (ORR)
      and key secondary endpoints of response duration and complete response (CR) rate.
      For patients with Hodgkin lymphoma, ORR was 73% (95% CI, 65-83%); median response
      duration was 6.7 months, and CR was 32% (95% CI, 23-42%). For patients with
      sALCL, ORR was 86% (95% CI, 77-95%), median response duration was 12.6 months,
      and CR was 57% (95% CI, 44-70%). The most common adverse reactions were
      neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper
      respiratory infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and
      vomiting. FDA granted accelerated approval of brentuximab vedotin for the
      treatment of patients with Hodgkin lymphoma after failure of autologous stem cell
      transplantation (ASCT) or after failure of at least two prior multiagent
      chemotherapy regimens in patients who are not ASCT candidates, and for the
      treatment of patients with sALCL after failure of at least one prior multiagent
      chemotherapy regimen.

PMID- 22962442
TI  - Retinal vein pulsation is in phase with intracranial pressure and not intraocular
      pressure.

PMID- 22962443
TI  - Context-specific transcriptional regulatory network inference from global gene
      expression maps using double two-way t-tests.
AB  - MOTIVATION: Transcriptional regulatory network inference methods have been
      studied for years. Most of them rely on complex mathematical and algorithmic
      concepts, making them hard to adapt, re-implement or integrate with other
      methods. To address this problem, we introduce a novel method based on a minimal
      statistical model for observing transcriptional regulatory interactions in noisy
      expression data, which is conceptually simple, easy to implement and integrate in
      any statistical software environment and equally well performing as existing
      methods. RESULTS: We developed a method to infer regulatory interactions based on
      a model where transcription factors (TFs) and their targets are both
      differentially expressed in a gene-specific, critical sample contrast, as
      measured by repeated two-way t-tests. Benchmarking on standard Escherichia coli
      and yeast reference datasets showed that this method performs equally well as the
      best existing methods. Analysis of the predicted interactions suggested that it
      works best to infer context-specific TF-target interactions which only co-express
      locally. We confirmed this hypothesis on a dataset of >1000 normal human tissue
      samples, where we found that our method predicts highly tissue-specific and
      functionally relevant interactions, whereas a global co-expression method only
      associates general TFs to non-specific biological processes. AVAILABILITY: A
      software tool called TwixTrix is available from http://twixtrix.googlecode.com.
      SUPPLEMENTARY INFORMATION: Supplementary Material is available from
      http://www.roslin.ed.ac.uk/tom-michoel/supplementary-data. CONTACT:
      tom.michoel@roslin.ed.ac.uk.

PMID- 22962444
TI  - ECCB 2012: The 11th European Conference on Computational Biology.

PMID- 22962446
TI  - Telescoper: de novo assembly of highly repetitive regions.
AB  - MOTIVATION: With advances in sequencing technology, it has become faster and
      cheaper to obtain short-read data from which to assemble genomes. Although there
      has been considerable progress in the field of genome assembly, producing high
      quality de novo assemblies from short-reads remains challenging, primarily
      because of the complex repeat structures found in the genomes of most higher
      organisms. The telomeric regions of many genomes are particularly difficult to
      assemble, though much could be gained from the study of these regions, as their
      evolution has not been fully characterized and they have been linked to aging.
      RESULTS: In this article, we tackle the problem of assembling highly repetitive
      regions by developing a novel algorithm that iteratively extends long paths
      through a series of read-overlap graphs and evaluates them based on a statistical
      framework. Our algorithm, Telescoper, uses short- and long-insert libraries in an
      integrated way throughout the assembly process. Results on real and simulated
      data demonstrate that our approach can effectively resolve much of the complex
      repeat structures found in the telomeres of yeast genomes, especially when longer
      long-insert libraries are used. AVAILABILITY: Telescoper is publicly available
      for download at sourceforge.net/p/telescoper. CONTACT: yss@eecs.berkeley.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962447
TI  - Long read alignment based on maximal exact match seeds.
AB  - MOTIVATION: The explosive growth of next-generation sequencing datasets poses a
      challenge to the mapping of reads to reference genomes in terms of alignment
      quality and execution speed. With the continuing progress of high-throughput
      sequencing technologies, read length is constantly increasing and many existing
      aligners are becoming inefficient as generated reads grow larger. RESULTS: We
      present CUSHAW2, a parallelized, accurate, and memory-efficient long read
      aligner. Our aligner is based on the seed-and-extend approach and uses maximal
      exact matches as seeds to find gapped alignments. We have evaluated and compared
      CUSHAW2 to the three other long read aligners BWA-SW, Bowtie2 and GASSST, by
      aligning simulated and real datasets to the human genome. The performance
      evaluation shows that CUSHAW2 is consistently among the highest-ranked aligners
      in terms of alignment quality for both single-end and paired-end alignment, while
      demonstrating highly competitive speed. Furthermore, our aligner shows good
      parallel scalability with respect to the number of CPU threads. AVAILABILITY:
      CUSHAW2, written in C++, and all simulated datasets are available at
      http://cushaw2.sourceforge.net CONTACT: liuy@uni-mainz.de; bertil.schmidt@uni
      mainz.de SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 22962448
TI  - Indel-tolerant read mapping with trinucleotide frequencies using cache-oblivious
      kd-trees.
AB  - MOTIVATION: Mapping billions of reads from next generation sequencing experiments
      to reference genomes is a crucial task, which can require hundreds of hours of
      running time on a single CPU even for the fastest known implementations.
      Traditional approaches have difficulties dealing with matches of large edit
      distance, particularly in the presence of frequent or large insertions and
      deletions (indels). This is a serious obstacle both in determining the spectrum
      and abundance of genetic variations and in personal genomics. RESULTS: For the
      first time, we adopt the approximate string matching paradigm of geometric
      embedding to read mapping, thus rephrasing it to nearest neighbor queries in a q
      gram frequency vector space. Using the L(1) distance between frequency vectors
      has the benefit of providing lower bounds for an edit distance with affine gap
      costs. Using a cache-oblivious kd-tree, we realize running times, which match the
      state-of-the-art. Additionally, running time and memory requirements are about
      constant for read lengths between 100 and 1000 bp. We provide a first proof-of
      concept that geometric embedding is a promising paradigm for read mapping and
      that L(1) distance might serve to detect structural variations. TreQ, our initial
      implementation of that concept, performs more accurate than many popular read
      mappers over a wide range of structural variants. AVAILABILITY AND
      IMPLEMENTATION: TreQ will be released under the GNU Public License (GPL), and
      precomputed genome indices will be provided for download at http://treq.sf.net.
      CONTACT: pavelm@cs.rutgers.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22962449
TI  - DELLY: structural variant discovery by integrated paired-end and split-read
      analysis.
AB  - MOTIVATION: The discovery of genomic structural variants (SVs) at high
      sensitivity and specificity is an essential requirement for characterizing
      naturally occurring variation and for understanding pathological somatic
      rearrangements in personal genome sequencing data. Of particular interest are
      integrated methods that accurately identify simple and complex rearrangements in
      heterogeneous sequencing datasets at single-nucleotide resolution, as an optimal
      basis for investigating the formation mechanisms and functional consequences of
      SVs. RESULTS: We have developed an SV discovery method, called DELLY, that
      integrates short insert paired-ends, long-range mate-pairs and split-read
      alignments to accurately delineate genomic rearrangements at single-nucleotide
      resolution. DELLY is suitable for detecting copy-number variable deletion and
      tandem duplication events as well as balanced rearrangements such as inversions
      or reciprocal translocations. DELLY, thus, enables to ascertain the full spectrum
      of genomic rearrangements, including complex events. On simulated data, DELLY
      compares favorably to other SV prediction methods across a wide range of
      sequencing parameters. On real data, DELLY reliably uncovers SVs from the 1000
      Genomes Project and cancer genomes, and validation experiments of randomly
      selected deletion loci show a high specificity. AVAILABILITY: DELLY is available
      at www.korbel.embl.de/software.html CONTACT: tobias.rausch@embl.de.

PMID- 22962450
TI  - Decoding properties of tRNA leave a detectable signal in codon usage bias.
AB  - MOTIVATION: The standard genetic code translates 61 codons into 20 amino acids
      using fewer than 61 transfer RNAs (tRNAs). This is possible because of the tRNA's
      ability to 'wobble' at the third base to decode more than one codon. Although the
      anticodon-codon mapping of tRNA to mRNA is a prerequisite for certain codon usage
      indices and can contribute to the understanding of the evolution of alternative
      genetic codes, it is usually not determined experimentally because such assays
      are prohibitively expensive and elaborate. Instead, the codon reading is
      approximated from theoretical inferences of nucleotide binding, the wobble rules.
      Unfortunately, these rules fail to capture all of the nuances of codon reading.
      This study addresses the codon reading properties of tRNAs and their evolutionary
      impact on codon usage bias. RESULTS: Using three different computational methods,
      the signal of tRNA decoding in codon usage bias is identified. The predictions by
      the methods generally agree with each other and compare well with experimental
      evidence of codon reading. This analysis suggests a revised codon reading for
      cytosolic tRNA in the yeast genome (Saccharomyces cerevisiae) that is more
      accurate than the common assignment by wobble rules. The results confirm the
      earlier observation that the wobble rules are not sufficient for a complete
      description of codon reading, because they depend on genome-specific factors. The
      computational methods presented here are applicable to any fully sequenced
      genome. AVAILABILITY: By request from the author. CONTACT: alexander.roth@isb
      sib.ch.

PMID- 22962451
TI  - Accurate estimation of short read mapping quality for next-generation genome
      sequencing.
AB  - MOTIVATION: Several software tools specialize in the alignment of short next
      generation sequencing reads to a reference sequence. Some of these tools report a
      mapping quality score for each alignment-in principle, this quality score tells
      researchers the likelihood that the alignment is correct. However, the reported
      mapping quality often correlates weakly with actual accuracy and the qualities of
      many mappings are underestimated, encouraging the researchers to discard correct
      mappings. Further, these low-quality mappings tend to correlate with variations
      in the genome (both single nucleotide and structural), and such mappings are
      important in accurately identifying genomic variants. APPROACH: We develop a
      machine learning tool, LoQuM (LOgistic regression tool for calibrating the
      Quality of short read mappings, to assign reliable mapping quality scores to
      mappings of Illumina reads returned by any alignment tool. LoQuM uses statistics
      on the read (base quality scores reported by the sequencer) and the alignment
      (number of matches, mismatches and deletions, mapping quality score returned by
      the alignment tool, if available, and number of mappings) as features for
      classification and uses simulated reads to learn a logistic regression model that
      relates these features to actual mapping quality. RESULTS: We test the
      predictions of LoQuM on an independent dataset generated by the ART short read
      simulation software and observe that LoQuM can 'resurrect' many mappings that are
      assigned zero quality scores by the alignment tools and are therefore likely to
      be discarded by researchers. We also observe that the recalibration of mapping
      quality scores greatly enhances the precision of called single nucleotide
      polymorphisms. AVAILABILITY: LoQuM is available as open source at
      http://compbio.case.edu/loqum/. CONTACT: matthew.ruffalo@case.edu.

PMID- 22962452
TI  - MetaCluster 5.0: a two-round binning approach for metagenomic data for low
      abundance species in a noisy sample.
AB  - MOTIVATION: Metagenomic binning remains an important topic in metagenomic
      analysis. Existing unsupervised binning methods for next-generation sequencing
      (NGS) reads do not perform well on (i) samples with low-abundance species or (ii)
      samples (even with high abundance) when there are many extremely low-abundance
      species. These two problems are common for real metagenomic datasets. Binning
      methods that can solve these problems are desirable. RESULTS: We proposed a two
      round binning method (MetaCluster 5.0) that aims at identifying both low
      abundance and high-abundance species in the presence of a large amount of noise
      due to many extremely low-abundance species. In summary, MetaCluster 5.0 uses a
      filtering strategy to remove noise from the extremely low-abundance species. It
      separate reads of high-abundance species from those of low-abundance species in
      two different rounds. To overcome the issue of low coverage for low-abundance
      species, multiple w values are used to group reads with overlapping w-mers,
      whereas reads from high-abundance species are grouped with high confidence based
      on a large w and then binning expands to low-abundance species using a relaxed
      (shorter) w. Compared to the recent tools, TOSS and MetaCluster 4.0, MetaCluster
      5.0 can find more species (especially those with low abundance of say 6* to 10*)
      and can achieve better sensitivity and specificity using less memory and running
      time. AVAILABILITY: http://i.cs.hku.hk/~alse/MetaCluster/ CONTACT:
      chin@cs.hku.hk.

PMID- 22962453
TI  - Stitching gene fragments with a network matching algorithm improves gene assembly
      for metagenomics.
AB  - MOTIVATION: One of the difficulties in metagenomic assembly is that homologous
      genes from evolutionarily closely related species may behave like repeats and
      confuse assemblers. As a result, small contigs, each representing a short gene
      fragment, instead of complete genes, may be reported by an assembler. This
      further complicates annotation of metagenomic datasets, as annotation tools (such
      as gene predictors or similarity search tools) typically perform poorly on
      configs encoding short gene fragments. RESULTS: We present a novel way of using
      the de Bruijn graph assembly of metagenomes to improve the assembly of genes. A
      network matching algorithm is proposed for matching the de Bruijn graph of
      contigs against reference genes, to derive 'gene paths' in the graph (sequences
      of contigs containing gene fragments) that have the highest similarities to known
      genes, allowing gene fragments contained in multiple contigs to be connected to
      form more complete (or intact) genes. Tests on simulated and real datasets show
      that our approach (called GeneStitch) is able to significantly improve the
      assembly of genes from metagenomic sequences, by connecting contigs with the
      guidance of homologous genes-information that is orthogonal to the sequencing
      reads. We note that the improvement of gene assembly can be observed even when
      only distantly related genes are available as the reference. We further propose
      to use 'gene graphs' to represent the assembly of reads from homologous genes and
      discuss potential applications of gene graphs to improving functional annotation
      for metagenomics. AVAILABILITY: The tools are available as open source for
      download at http://omics.informatics.indiana.edu/GeneStitch CONTACT:
      yye@indiana.edu.

PMID- 22962454
TI  - An exome sequencing pipeline for identifying and genotyping common CNVs
      associated with disease with application to psoriasis.
AB  - MOTIVATION: Despite the prevalence of copy number variation (CNV) in the human
      genome, only a handful of confirmed associations have been reported between
      common CNVs and complex disease. This may be partially attributed to the
      difficulty in accurately genotyping CNVs in large cohorts using array-based
      technologies. Exome sequencing is now widely being applied to case-control
      cohorts and presents an exciting opportunity to look for common CNVs associated
      with disease. RESULTS: We developed ExoCNVTest: an exome sequencing analysis
      pipeline to identify disease-associated CNVs and to generate absolute copy number
      genotypes at putatively associated loci. Our method re-discovered the LCE3B_LCE3C
      CNV association with psoriasis (P-value = 5 * 10e-6) while controlling inflation
      of test statistics (lambda < 1). ExoCNVTest-derived absolute CNV genotypes were
      97.4% concordant with PCR-derived genotypes at this locus. AVAILABILITY AND
      IMPLEMENTATION: ExoCNVTest has been implemented in Java and R and is freely
      available from www1.imperial.ac.uk/medicine/people/l.coin/. CONTACT:
      wangj@genomics.org.cn or Lachlan.J.M.Coin@genomics.org.cn.

PMID- 22962455
TI  - Nonlinear dimension reduction with Wright-Fisher kernel for genotype aggregation
      and association mapping.
AB  - MOTIVATION: Association tests based on next-generation sequencing data are often
      under-powered due to the presence of rare variants and large amount of neutral or
      protective variants. A successful strategy is to aggregate genetic information
      within meaningful single-nucleotide polymorphism (SNP) sets, e.g. genes or
      pathways, and test association on SNP sets. Many existing methods for group-wise
      tests require specific assumptions about the direction of individual SNP effects
      and/or perform poorly in the presence of interactions. RESULTS: We propose a
      joint association test strategy based on two key components: a nonlinear
      supervised dimension reduction approach for effective SNP information aggregation
      and a novel kernel specially designed for qualitative genotype data. The new test
      demonstrates superior performance in identifying causal genes over existing
      methods across a large variety of disease models simulated from sequence data of
      real genes. In general, the proposed method provides an association test strategy
      that can (i) detect both rare and common causal variants, (ii) deal with both
      additive and interaction effect, (iii) handle both quantitative traits and
      disease dichotomies and (iv) incorporate non-genetic covariates. In addition, the
      new kernel can potentially boost the power of the entire family of kernel-based
      methods for genetic data analysis. AVAILABILITY: The method is implemented in
      MATLAB. Source code is available upon request. CONTACT: hongjie.zhu@duke.edu.

PMID- 22962456
TI  - Evolution of gene neighborhoods within reconciled phylogenies.
AB  - MOTIVATION: Most models of genome evolution integrating gene duplications, losses
      and chromosomal rearrangements are computationally intract  able, even when
      comparing only two genomes. This prevents large-scale studies that consider
      different types of genome structural variations. RESULTS: We define an 'adjacency
      phylogenetic tree' that describes the evolution of an adjacency, a neighborhood
      relation between two genes, by speciation, duplication or loss of one or both
      genes, and rearrangement. We describe an algorithm that, given a species tree and
      a set of gene trees where the leaves are connected by adjacencies, computes an
      adjacency forest that minimizes the number of gains and breakages of adjacencies
      (caused by rearrangements) and runs in polynomial time. We use this algorithm to
      reconstruct contiguous regions of mammalian and plant ancestral genomes in a few
      minutes for a dozen species and several thousand genes. We show that this method
      yields reduced conflict between ancestral adjacencies. We detect duplications
      involving several genes and compare the different modes of evolution between
      phyla and among lineages. AVAILABILITY: C++ implementation using BIO++ package,
      available upon request to Severine Berard. CONTACT: Severine.Berard@cirad.fr or
      Eric.Tannier@inria.fr SUPPLEMENTARY INFORMATION: Supplementary material is
      available at Bioinformatics online.

PMID- 22962457
TI  - Uncovering the co-evolutionary network among prokaryotic genes.
AB  - MOTIVATION: Correlated events of gains and losses enable inference of co
      evolution relations. The reconstruction of the co-evolutionary interactions
      network in prokaryotic species may elucidate functional associations among genes.
      RESULTS: We developed a novel probabilistic methodology for the detection of co
      evolutionary interactions between pairs of genes. Using this method we inferred
      the co-evolutionary network among 4593 Clusters of Orthologous Genes (COGs). The
      number of co-evolutionary interactions substantially differed among COGs. Over
      40% were found to co-evolve with at least one partner. We partitioned the network
      of co-evolutionary relations into clusters and uncovered multiple modular
      assemblies of genes with clearly defined functions. Finally, we measured the
      extent to which co-evolutionary relations coincide with other cellular relations
      such as genomic proximity, gene fusion propensity, co-expression, protein-protein
      interactions and metabolic connections. Our results show that co-evolutionary
      relations only partially overlap with these other types of networks. Our results
      suggest that the inferred co-evolutionary network in prokaryotes is highly
      informative towards revealing functional relations among genes, often showing
      signals that cannot be extracted from other network types. AVAILABILITY AND
      IMPLEMENTATION: Available under GPL license as open source. CONTACT:
      talp@post.tau.ac.il. SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 22962458
TI  - Genomic context analysis reveals dense interaction network between vertebrate
      ultraconserved non-coding elements.
AB  - MOTIVATION: Genomic context analysis, also known as phylogenetic profiling, is
      widely used to infer functional interactions between proteins but rarely applied
      to non-coding cis-regulatory DNA elements. We were wondering whether this
      approach could provide insights about utlraconserved non-coding elements (UCNEs).
      These elements are organized as large clusters, so-called gene regulatory blocks
      (GRBs) around key developmental genes. Their molecular functions and the reasons
      for their high degree of conservation remain enigmatic. RESULTS: In a special
      setting of genomic context analysis, we analyzed the fate of GRBs after a whole
      genome duplication event in five fish genomes. We found that in most cases all
      UCNEs were retained together as a single block, whereas the corresponding target
      genes were often retained in two copies, one completely devoid of UCNEs. This
      'winner-takes-all' pattern suggests that UCNEs of a GRB function in a highly
      cooperative manner. We propose that the multitude of interactions between UCNEs
      is the reason for their extreme sequence conservation. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online and at http://ccg.vital
      it.ch/ucne/

PMID- 22962459
TI  - Fractionation, rearrangement and subgenome dominance.
AB  - MOTIVATION: Fractionation is arguably the greatest cause of gene order disruption
      following whole genome duplication, causing severe biases in chromosome
      rearrangement-based estimates of evolutionary divergence. RESULTS: We show how to
      correct for this bias almost entirely by means of a 'consolidation' algorithm for
      detecting and suitably transforming identifiable regions of fractionation. We
      characterize the process of fractionation and the performance of the algorithm
      through realistic simulations. We apply our method to a number of core eudicot
      genomes, we and by studying the fractionation regions detected, are able to
      address topical issues in polyploid evolution. AVAILABILITY AND IMPLEMENTATION:
      Code for the consolidation algorithm, and sample data, is available at:
      http://137.122.149.195/Software/Fractionation/fractionation.html CONTACT:
      sankoff@uottawa.ca.

PMID- 22962460
TI  - Inferring duplications, losses, transfers and incomplete lineage sorting with
      nonbinary species trees.
AB  - MOTIVATION: Gene duplication (D), transfer (T), loss (L) and incomplete lineage
      sorting (I) are crucial to the evolution of gene families and the emergence of
      novel functions. The history of these events can be inferred via comparison of
      gene and species trees, a process called reconciliation, yet current
      reconciliation algorithms model only a subset of these evolutionary processes.
      RESULTS: We present an algorithm to reconcile a binary gene tree with a nonbinary
      species tree under a DTLI parsimony criterion. This is the first reconciliation
      algorithm to capture all four evolutionary processes driving tree incongruence
      and the first to reconcile non-binary species trees with a transfer model. Our
      algorithm infers all optimal solutions and reports complete, temporally feasible
      event histories, giving the gene and species lineages in which each event
      occurred. It is fixed-parameter tractable, with polytime complexity when the
      maximum species outdegree is fixed. Application of our algorithms to prokaryotic
      and eukaryotic data show that use of an incomplete event model has substantial
      impact on the events inferred and resulting biological conclusions. AVAILABILITY:
      Our algorithms have been implemented in Notung, a freely available phylogenetic
      reconciliation software package, available at
      http://www.cs.cmu.edu/~durand/Notung. CONTACT: mstolzer@andrew.cmu.edu.

PMID- 22962461
TI  - Multiple instance learning of Calmodulin binding sites.
AB  - MOTIVATION: Calmodulin (CaM) is a ubiquitously conserved protein that acts as a
      calcium sensor, and interacts with a large number of proteins. Detection of CaM
      binding proteins and their interaction sites experimentally requires a
      significant effort, so accurate methods for their prediction are important.
      RESULTS: We present a novel algorithm (MI-1 SVM) for binding site prediction and
      evaluate its performance on a set of CaM-binding proteins extracted from the
      Calmodulin Target Database. Our approach directly models the problem of binding
      site prediction as a large-margin classification problem, and is able to take
      into account uncertainty in binding site location. We show that the proposed
      algorithm performs better than the standard SVM formulation, and illustrate its
      ability to recover known CaM binding motifs. A highly accurate cascaded
      classification approach using the proposed binding site prediction method to
      predict CaM binding proteins in Arabidopsis thaliana is also presented.
      AVAILABILITY: Matlab code for training MI-1 SVM and the cascaded classification
      approach is available on request. CONTACT: fayyazafsar@gmail.com or
      asa@cs.colostate.edu.

PMID- 22962462
TI  - Side-chain rotamer changes upon ligand binding: common, crucial, correlate with
      entropy and rearrange hydrogen bonding.
AB  - MOTIVATION: Protein movements form a continuum from large domain rearrangements
      (including folding and restructuring) to side-chain rotamer changes and small
      rearrangements. Understanding side-chain flexibility upon binding is important to
      understand molecular recognition events and predict ligand binding. METHODS: In
      the present work, we developed a well-curated non-redundant dataset of 188
      proteins in pairs of structures in the Apo (unbound) and Holo (bound) forms to
      study the extent and the factors that guide side-chain rotamer changes upon
      binding. RESULTS: Our analysis shows that side-chain rotamer changes are
      widespread with only 10% of binding sites displaying no conformational changes.
      Overall, at most five rotamer changes account for the observed movements in 90%
      of the cases. Furthermore, rotamer changes are essential in 32% of flexible
      binding sites. The different amino acids have a 11-fold difference in their
      probability to undergo changes. Side-chain flexibility represents an intrinsic
      property of amino acids as it correlates well with configurational entropy
      differences. Furthermore, on average b-factors and solvent accessible surface
      areas can discriminate flexible side-chains in the Apo form. Finally, there is a
      rearrangement of the hydrogen-bonding network upon binding primarily with a loss
      of H-bonds with water molecules and a gain of H-bonds with protein residues for
      flexible residues. Interestingly, only 25% of side chains capable of forming H
      bonds do so with the ligand upon binding. In terms of drug design, this last
      result shows that there is a large number of potential interactions that may be
      exploited to modulate the specificity and sensitivity of inhibitors. CONTACT:
      rafael.najmanovich@usherbrooke.ca.

PMID- 22962463
TI  - A structure-based protocol for learning the family-specific mechanisms of
      membrane-binding domains.
AB  - MOTIVATION: Peripheral membrane-targeting domain (MTD) families, such as C1-, C2-
      and PH domains, play a key role in signal transduction and membrane trafficking
      by dynamically translocating their parent proteins to specific plasma membranes
      when changes in lipid composition occur. It is, however, difficult to determine
      the subset of domains within families displaying this property, as sequence
      motifs signifying the membrane binding properties are not well defined. For this
      reason, procedures based on sequence similarity alone are often insufficient in
      computational identification of MTDs within families (yielding less than 65%
      accuracy even with a sequence identity of 70%). RESULTS: We present a machine
      learning protocol for determining membrane-targeting properties achieving 85-90%
      accuracy in separating binding and non-binding domains within families. Our model
      is based on features from both sequence and structure, thereby incorporation
      statistics obtained from the entire domain family and domain-specific physical
      quantities such as surface electrostatics. In addition, by using the enriched
      rules in alternating decision tree classifiers, we are able to determine the
      meaning of the assigned function labels in terms of biological mechanisms.
      CONCLUSIONS: The high accuracy of the learned models and good agreement between
      the rules discovered using the ADtree classifier and mechanisms reported in the
      literature reflect the value of machine learning protocols in both prediction and
      biological knowledge discovery. Our protocol can thus potentially be used as a
      general function annotation and knowledge mining tool for other protein domains.
      AVAILABILITY: metador.bioengr.uic.edu CONTACT: huilu@uic.edu.

PMID- 22962464
TI  - SANS: high-throughput retrieval of protein sequences allowing 50% mismatches.
AB  - MOTIVATION: The genomic era in molecular biology has brought on a rapidly
      widening gap between the amount of sequence data and first-hand experimental
      characterization of proteins. Fortunately, the theory of evolution provides a
      simple solution: functional and structural information can be transferred between
      homologous proteins. Sequence similarity searching followed by k-nearest neighbor
      classification is the most widely used tool to predict the function or structure
      of anonymous gene products that come out of genome sequencing projects. RESULTS:
      We present a novel word filter, suffix array neighborhood search (SANS), to
      identify protein sequence similarities in the range of 50-100% identity with
      sensitivity comparable to BLAST and 10 times the speed of USEARCH. In contrast to
      these previous approaches, the complexity of the search is proportional only to
      the length of the query sequence and independent of database size, enabling fast
      searching and functional annotation into the future despite rapidly expanding
      databases. AVAILABILITY AND IMPLEMENTATION: The software is freely available to
      non-commercial users from our website
      http://ekhidna.biocenter.helsinki.fi/downloads/sans. CONTACT:
      liisa.holm@helsinki.fi.

PMID- 22962465
TI  - Protein domain recurrence and order can enhance prediction of protein functions.
AB  - MOTIVATION: Burgeoning sequencing technologies have generated massive amounts of
      genomic and proteomic data. Annotating the functions of proteins identified in
      this data has become a big and crucial problem. Various computational methods
      have been developed to infer the protein functions based on either the sequences
      or domains of proteins. The existing methods, however, ignore the recurrence and
      the order of the protein domains in this function inference. RESULTS: We
      developed two new methods to infer protein functions based on protein domain
      recurrence and domain order. Our first method, DRDO, calculates the posterior
      probability of the Gene Ontology terms based on domain recurrence and domain
      order information, whereas our second method, DRDO-NB, relies on the naive Bayes
      methodology using the same domain architecture information. Our large-scale
      benchmark comparisons show strong improvements in the accuracy of the protein
      function inference achieved by our new methods, demonstrating that domain
      recurrence and order can provide important information for inference of protein
      functions. AVAILABILITY: The new models are provided as open source programs at
      http://sfb.kaust.edu.sa/Pages/Software.aspx. CONTACT: dkihara@cs.purdue.edu,
      xin.gao@kaust.edu.sa SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics Online.

PMID- 22962466
TI  - EnrichNet: network-based gene set enrichment analysis.
AB  - MOTIVATION: Assessing functional associations between an experimentally derived
      gene or protein set of interest and a database of known gene/protein sets is a
      common task in the analysis of large-scale functional genomics data. For this
      purpose, a frequently used approach is to apply an over-representation-based
      enrichment analysis. However, this approach has four drawbacks: (i) it can only
      score functional associations of overlapping gene/proteins sets; (ii) it
      disregards genes with missing annotations; (iii) it does not take into account
      the network structure of physical interactions between the gene/protein sets of
      interest and (iv) tissue-specific gene/protein set associations cannot be
      recognized. RESULTS: To address these limitations, we introduce an integrative
      analysis approach and web-application called EnrichNet. It combines a novel graph
      based statistic with an interactive sub-network visualization to accomplish two
      complementary goals: improving the prioritization of putative functional
      gene/protein set associations by exploiting information from molecular
      interaction networks and tissue-specific gene expression data and enabling a
      direct biological interpretation of the results. By using the approach to analyse
      sets of genes with known involvement in human diseases, new pathway associations
      are identified, reflecting a dense sub-network of interactions between their
      corresponding proteins. AVAILABILITY: EnrichNet is freely available at
      http://www.enrichnet.org. CONTACT: Natalio.Krasnogor@nottingham.ac.uk,
      reinhard.schneider@uni.lu or avalencia@cnio.es SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics Online.

PMID- 22962467
TI  - LocTree2 predicts localization for all domains of life.
AB  - MOTIVATION: Subcellular localization is one aspect of protein function. Despite
      advances in high-throughput imaging, localization maps remain incomplete. Several
      methods accurately predict localization, but many challenges remain to be
      tackled. RESULTS: In this study, we introduced a framework to predict
      localization in life's three domains, including globular and membrane proteins (3
      classes for archaea; 6 for bacteria and 18 for eukaryota). The resulting method,
      LocTree2, works well even for protein fragments. It uses a hierarchical system of
      support vector machines that imitates the cascading mechanism of cellular
      sorting. The method reaches high levels of sustained performance (eukaryota:
      Q18=65%, bacteria: Q6=84%). LocTree2 also accurately distinguishes membrane and
      non-membrane proteins. In our hands, it compared favorably with top methods when
      tested on new data. AVAILABILITY: Online through PredictProtein
      (predictprotein.org); as standalone version at
      http://www.rostlab.org/services/loctree2. CONTACT: localization@rostlab.org
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962468
TI  - Techniques to cope with missing data in host-pathogen protein interaction
      prediction.
AB  - MOTIVATION: Approaches that use supervised machine learning techniques for
      protein-protein interaction (PPI) prediction typically use features obtained by
      integrating several sources of data. Often certain attributes of the data are not
      available, resulting in missing values. In particular, our host-pathogen PPI
      datasets have a large fraction, in the range of 58-85% of missing values, which
      makes it challenging to apply machine learning algorithms. RESULTS: We show that
      specialized techniques for missing value imputation can improve the performance
      of the models significantly. We use cross species information in combination with
      machine learning techniques like Group lasso with l(1)/l(2) regularization. We
      demonstrate the benefits of our approach on two PPI prediction problems. In our
      first example of Salmonella-human PPI prediction, we are able to obtain high
      prediction accuracies with 77.6% precision and 84% recall. Comparison with
      various other techniques shows an improvement of 9 in F1 score over the next best
      technique. We also apply our method to Yersinia-human PPI prediction
      successfully, demonstrating the generality of our approach. AVAILABILITY:
      Predicted interactions, datasets, features are available at:
      http://www.cs.cmu.edu/~mkshirsa/eccb2012_paper46.html. CONTACT:
      judithks@cs.cmu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 22962469
TI  - Identifying functional modules in interaction networks through overlapping Markov
      clustering.
AB  - MOTIVATION: In recent years, Markov clustering (MCL) has emerged as an effective
      algorithm for clustering biological networks-for instance clustering protein
      protein interaction (PPI) networks to identify functional modules. However, a
      limitation of MCL and its variants (e.g. regularized MCL) is that it only
      supports hard clustering often leading to an impedance mismatch given that there
      is often a significant overlap of proteins across functional modules. RESULTS: In
      this article, we seek to redress this limitation. We propose a soft variation of
      Regularized MCL (R-MCL) based on the idea of iteratively (re-)executing R-MCL
      while ensuring that multiple executions do not always converge to the same
      clustering result thus allowing for highly overlapped clusters. The resulting
      algorithm, denoted soft regularized Markov clustering, is shown to outperform a
      range of extant state-of-the-art approaches in terms of accuracy of identifying
      functional modules on three real PPI networks. AVAILABILITY: All data and codes
      are freely available upon request. CONTACT: srini@cse.ohio-state.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962470
TI  - Graphlet-based edge clustering reveals pathogen-interacting proteins.
AB  - MOTIVATION: Prediction of protein function from protein interaction networks has
      received attention in the post-genomic era. A popular strategy has been to
      cluster the network into functionally coherent groups of proteins and assign the
      entire cluster with a function based on functions of its annotated members.
      Traditionally, network research has focused on clustering of nodes. However,
      clustering of edges may be preferred: nodes belong to multiple functional groups,
      but clustering of nodes typically cannot capture the group overlap, while
      clustering of edges can. Clustering of adjacent edges that share many neighbors
      was proposed recently, outperforming different node clustering methods. However,
      since some biological processes can have characteristic 'signatures' throughout
      the network, not just locally, it may be of interest to consider edges that are
      not necessarily adjacent. RESULTS: We design a sensitive measure of the
      'topological similarity' of edges that can deal with edges that are not
      necessarily adjacent. We cluster edges that are similar according to our measure
      in different baker's yeast protein interaction networks, outperforming existing
      node and edge clustering approaches. We apply our approach to the human network
      to predict new pathogen-interacting proteins. This is important, since these
      proteins represent drug target candidates. AVAILABILITY: Software executables are
      freely available upon request. CONTACT: tmilenko@nd.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22962471
TI  - Identification of chemogenomic features from drug-target interaction networks
      using interpretable classifiers.
AB  - MOTIVATION: Drug effects are mainly caused by the interactions between drug
      molecules and their target proteins including primary targets and off-targets.
      Identification of the molecular mechanisms behind overall drug-target
      interactions is crucial in the drug design process. RESULTS: We develop a
      classifier-based approach to identify chemogenomic features (the underlying
      associations between drug chemical substructures and protein domains) that are
      involved in drug-target interaction networks. We propose a novel algorithm for
      extracting informative chemogenomic features by using L(1) regularized
      classifiers over the tensor product space of possible drug-target pairs. It is
      shown that the proposed method can extract a very limited number of chemogenomic
      features without loosing the performance of predicting drug-target interactions
      and the extracted features are biologically meaningful. The extracted
      substructure-domain association network enables us to suggest ligand chemical
      fragments specific for each protein domain and ligand core substructures
      important for a wide range of protein families. AVAILABILITY: Softwares are
      available at the supplemental website. CONTACT: yamanishi@bioreg.kyushu-u.ac.jp
      SUPPLEMENTARY INFORMATION: Datasets and all results are available at
      http://cbio.ensmp.fr/~yyamanishi/l1binary/  .

PMID- 22962472
TI  - Boolean approach to signalling pathway modelling in HGF-induced keratinocyte
      migration.
AB  - MOTIVATION: Cell migration is a complex process that is controlled through the
      time-sequential feedback regulation of protein signalling and gene regulation.
      Based on prior knowledge and own experimental data, we developed a large-scale
      dynamic network describing the onset and maintenance of hepatocyte growth factor
      induced migration of primary human keratinocytes. We applied Boolean logic to
      capture the qualitative behaviour as well as short-and long-term dynamics of the
      complex signalling network involved in this process, comprising protein
      signalling, gene regulation and autocrine feedback. RESULTS: A Boolean model has
      been compiled from time-resolved transcriptome data and literature mining,
      incorporating the main pathways involved in migration from initial stimulation to
      phenotype progress. Steady-state analysis under different inhibition and
      stimulation conditions of known key molecules reproduces existing data and
      predicts novel interactions based on our own experiments. Model simulations
      highlight for the first time the necessity of a temporal sequence of initial,
      transient MET receptor (met proto-oncogene, hepatocyte growth factor receptor)
      and subsequent, continuous epidermal growth factor/integrin signalling to trigger
      and sustain migration by autocrine signalling that is integrated through the
      Focal adhesion kinase protein. We predicted in silico and verified in vitro that
      long-term cell migration is stopped if any of the two feedback loops are
      inhibited. AVAILABILITY: The network file for analysis with the R BoolNet library
      is available in the Supplementary Information. CONTACT:
      melanie.boerries@frias.uni-freiburg.de or hauke.busch@frias.uni-freiburg.de
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962473
TI  - Stoichiometric capacitance reveals the theoretical capabilities of metabolic
      networks.
AB  - MOTIVATION: Metabolic engineering aims at modulating the capabilities of
      metabolic networks by changing the activity of biochemical reactions. The
      existing constraint-based approaches for metabolic engineering have proven
      useful, but are limited only to reactions catalogued in various pathway
      databases. RESULTS: We consider the alternative of designing synthetic strategies
      which can be used not only to characterize the maximum theoretically possible
      product yield but also to engineer networks with optimal conversion capability by
      using a suitable biochemically feasible reaction called 'stoichiometric
      capacitance'. In addition, we provide a theoretical solution for decomposing a
      given stoichiometric capacitance over a set of known enzymatic reactions. We
      determine the stoichiometric capacitance for genome-scale metabolic networks of
      10 organisms from different kingdoms of life and examine its implications for the
      alterations in flux variability patterns. Our empirical findings suggest that the
      theoretical capacity of metabolic networks comes at a cost of dramatic system's
      changes. CONTACT: larhlimi@mpimp-golm.mpg.de, or nikoloski@mpimp-golm.mpg.de
      SUPPLEMENTARY INFORMATION: Supplementary tables are available at Bioinformatics
      online.

PMID- 22962474
TI  - The architecture of the gene regulatory networks of different tissues.
AB  - SUMMARY: The great variety of human cell types in morphology and function is due
      to the diverse gene expression profiles that are governed by the distinctive
      regulatory networks in different cell types. It is still a challenging task to
      explain how the regulatory networks achieve the diversity of different cell
      types. Here, we report on our studies of the design principles of the tissue
      regulatory system by constructing the regulatory networks of eight human tissues,
      which subsume the regulatory interactions between transcription factors (TFs),
      microRNAs (miRNAs) and non-TF target genes. The results show that there are in
      /out-hubs of high in-/out-degrees in tissue networks. Some hubs (strong hubs)
      maintain the hub status in all the tissues where they are expressed, whereas
      others (weak hubs), in spite of their ubiquitous expression, are hubs only in
      some tissues. The network motifs are mostly feed-forward loops. Some of them
      having no miRNAs are the common motifs shared by all tissues, whereas the others
      containing miRNAs are the tissue-specific ones owned by one or several tissues,
      indicating that the transcriptional regulation is more conserved across tissues
      than the post-transcriptional regulation. In particular, a common bow-tie
      framework was found that underlies the motif instances and shows diverse patterns
      in different tissues. Such bow-tie framework reflects the utilization efficiency
      of the regulatory system as well as its high variability in different tissues,
      and could serve as the model to further understand the structural adaptation of
      the regulatory system to the specific requirements of different cell functions.
      CONTACT: edgar.wingender@bioinf.med.uni-goettingen.de; jwang@nju.edu.cn
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962475
TI  - Random sampling of elementary flux modes in large-scale metabolic networks.
AB  - MOTIVATION: The description of a metabolic network in terms of elementary (flux)
      modes (EMs) provides an important framework for metabolic pathway analysis.
      However, their application to large networks has been hampered by the
      combinatorial explosion in the number of modes. In this work, we develop a method
      for generating random samples of EMs without computing the whole set. RESULTS:
      Our algorithm is an adaptation of the canonical basis approach, where we add an
      additional filtering step which, at each iteration, selects a random subset of
      the new combinations of modes. In order to obtain an unbiased sample, all
      candidates are assigned the same probability of getting selected. This approach
      avoids the exponential growth of the number of modes during computation, thus
      generating a random sample of the complete set of EMs within reasonable time. We
      generated samples of different sizes for a metabolic network of Escherichia coli,
      and observed that they preserve several properties of the full EM set. It is also
      shown that EM sampling can be used for rational strain design. A well distributed
      sample, that is representative of the complete set of EMs, should be suitable to
      most EM-based methods for analysis and optimization of metabolic networks.
      AVAILABILITY: Source code for a cross-platform implementation in Python is freely
      available at http://code.google.com/p/emsampler. CONTACT: dmachado@deb.uminho.pt
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962476
TI  - Relating drug-protein interaction network with drug side effects.
AB  - MOTIVATION: Identifying the emergence and underlying mechanisms of drug side
      effects is a challenging task in the drug development process. This underscores
      the importance of system-wide approaches for linking different scales of drug
      actions; namely drug-protein interactions (molecular scale) and side effects
      (phenotypic scale) toward side effect prediction for uncharacterized drugs.
      RESULTS: We performed a large-scale analysis to extract correlated sets of
      targeted proteins and side effects, based on the co-occurrence of drugs in
      protein-binding profiles and side effect profiles, using sparse canonical
      correlation analysis. The analysis of 658 drugs with the two profiles for 1368
      proteins and 1339 side effects led to the extraction of 80 correlated sets.
      Enrichment analyses using KEGG and Gene Ontology showed that most of the
      correlated sets were significantly enriched with proteins that are involved in
      the same biological pathways, even if their molecular functions are different.
      This allowed for a biologically relevant interpretation regarding the
      relationship between drug-targeted proteins and side effects. The extracted side
      effects can be regarded as possible phenotypic outcomes by drugs targeting the
      proteins that appear in the same correlated set. The proposed method is expected
      to be useful for predicting potential side effects of new drug candidate
      compounds based on their protein-binding profiles. SUPPLEMENTARY INFORMATION:
      Datasets and all results are available at http://web.kuicr.kyoto
      u.ac.jp/supp/smizutan/target-effect/. AVAILABILITY: Software is available at the
      above supplementary website. CONTACT: yamanishi@bioreg.kyushu-u.ac.jp, or
      goto@kuicr.kyoto-u.ac.jp.

PMID- 22962477
TI  - Comprehensive estimation of input signals and dynamics in biochemical reaction
      networks.
AB  - MOTIVATION: Cellular information processing can be described mathematically using
      differential equations. Often, external stimulation of cells by compounds such as
      drugs or hormones leading to activation has to be considered. Mathematically, the
      stimulus is represented by a time-dependent input function. Parameters such as
      rate constants of the molecular interactions are often unknown and need to be
      estimated from experimental data, e.g. by maximum likelihood estimation. For this
      purpose, the input function has to be defined for all times of the integration
      interval. This is usually achieved by approximating the input by interpolation or
      smoothing of the measured data. This procedure is suboptimal since the input
      uncertainties are not considered in the estimation process which often leads to
      overoptimistic confidence intervals of the inferred parameters and the model
      dynamics. RESULTS: This article presents a new approach which includes the input
      estimation into the estimation process of the dynamical model parameters by
      minimizing an objective function containing all parameters simultaneously. We
      applied this comprehensive approach to an illustrative model with simulated data
      and compared it to alternative methods. Statistical analyses revealed that our
      method improves the prediction of the model dynamics and the confidence intervals
      leading to a proper coverage of the confidence intervals of the dynamic
      parameters. The method was applied to the JAK-STAT signaling pathway.
      AVAILABILITY: MATLAB code is available on the authors' website
      http://www.fdmold.uni-freiburg.de/~schelker/. CONTACT: max.schelker@fdm.uni
      freiburg.de SUPPLEMENTARY INFORMATION: Additional information is available at
      Bioinformatics Online.

PMID- 22962478
TI  - Trajectory-oriented Bayesian experiment design versus Fisher A-optimal design: an
      in depth comparison study.
AB  - MOTIVATION: Experiment design strategies for biomedical models with the purpose
      of parameter estimation or model discrimination are in the focus of intense
      research. Experimental limitations such as sparse and noisy data result in
      unidentifiable parameters and render-related design tasks challenging problems.
      Often, the temporal resolution of data is a limiting factor and the amount of
      possible experimental interventions is finite. To address this issue, we propose
      a Bayesian experiment design algorithm to minimize the prediction uncertainty for
      a given set of experiments and compare it to traditional A-optimal design.
      RESULTS: In an in depth numerical study involving an ordinary differential
      equation model of the trans-Golgi network with 12 partly non-identifiable
      parameters, we minimized the prediction uncertainty efficiently for predefined
      scenarios. The introduced method results in twice the prediction precision as the
      same amount of A-optimal designed experiments while introducing a useful stopping
      criterion. The simulation intensity of the algorithm's major design step is
      thereby reasonably affordable. Besides smaller variances in the predicted
      trajectories compared with Fisher design, we could also achieve smaller parameter
      posterior distribution entropies, rendering this method superior to A-optimal
      Fisher design also in the parameter space. AVAILABILITY: Necessary
      software/toolbox information are available in the supplementary material. The
      project script including example data can be downloaded from http://www.ist.uni
      stuttgart.de/%7eweber/BayesFisher2012. CONTACT: patrick.weber@ist.uni
      stuttgart.de SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 22962479
TI  - REVEAL--visual eQTL analytics.
AB  - MOTIVATION: The analysis of expression quantitative trait locus (eQTL) data is a
      challenging scientific endeavor, involving the processing of very large,
      heterogeneous and complex data. Typical eQTL analyses involve three types of
      data: sequence-based data reflecting the genotypic variations, gene expression
      data and meta-data describing the phenotype. Based on these, certain genotypes
      can be connected with specific phenotypic outcomes to infer causal associations
      of genetic variation, expression and disease. To this end, statistical methods
      are used to find significant associations between single nucleotide polymorphisms
      (SNPs) or pairs of SNPs and gene expression. A major challenge lies in
      summarizing the large amount of data as well as statistical results and to
      generate informative, interactive visualizations. RESULTS: We present Reveal, our
      visual analytics approach to this challenge. We introduce a graph-based
      visualization of associations between SNPs and gene expression and a detailed
      genotype view relating summarized patient cohort genotypes with data from
      individual patients and statistical analyses. AVAILABILITY: Reveal is included in
      Mayday, our framework for visual exploration and analysis. It is available at
      http://it.inf.uni-tuebingen.de/software/reveal/. CONTACT: guenter.jaeger@uni
      tuebingen.de.

PMID- 22962480
TI  - Hybrid spatial Gillespie and particle tracking simulation.
AB  - MOTIVATION: Cellular signal transduction involves spatial-temporal dynamics and
      often stochastic effects due to the low particle abundance of some molecular
      species. Others can, however, be of high abundances. Such a system can be
      simulated either with the spatial Gillespie/Stochastic Simulation Algorithm (SSA)
      or Brownian/Smoluchowski dynamics if space and stochasticity are important. To
      combine the accuracy of particle-based methods with the superior performance of
      the SSA, we suggest a hybrid simulation. RESULTS: The proposed simulation allows
      an interactive or automated switching for regions or species of interest in the
      cell. Especially we see an application if for instance receptor clustering at the
      membrane is modeled in detail and the transport through the cytoplasm is included
      as well. The results show the increase in performance of the overall simulation,
      and the limits of the approach if crowding is included. Future work will include
      the development of a GUI to improve control of the simulation. AVAILABILITY OF
      IMPLEMENTATION: www.bison.ethz.ch/research/spatial_simulations. CONTACT:
      mklann@ee.ethz.ch or koeppl@ethz.ch Supplementary/Information: Supplementary data
      are available at Bioinformatics online.

PMID- 22962481
TI  - Imaging, quantification and visualization of spatio-temporal patterning in mESC
      colonies under different culture conditions.
AB  - MOTIVATION: Mouse embryonic stem cells (mESCs) have developed into a prime system
      to study the regulation of pluripotency in stable cell lines. It is well
      recognized that different, established protocols for the maintenance of mESC
      pluripotency support morphologically and functionally different cell cultures.
      However, it is unclear how characteristic properties of cell colonies develop
      over time and how they are re-established after cell passage depending on the
      culture conditions. Furthermore, it appears that cell colonies have an internal
      structure with respect to cell size, marker expression or biomechanical
      properties, which is not sufficiently understood. The analysis of these
      phenotypic properties is essential for a comprehensive understanding of mESC
      development and ultimately requires a bioinformatics approach to guarantee
      reproducibility and high-throughput data analysis. RESULTS: We developed an
      automated image analysis and colony tracking framework to obtain an objective and
      reproducible quantification of structural properties of cell colonies as they
      evolve in space and time. In particular, we established a method that quantifies
      changes in colony shape and (internal) motion using fluid image registration and
      image segmentation. The methodology also allows to robustly track motion,
      splitting and merging of colonies over a sequence of images. Our results provide
      a first quantitative assessment of temporal mESC colony formation and estimates
      of structural differences between colony growth under different culture
      conditions. Furthermore, we provide a stream-based visualization of structural
      features of individual colonies over time for the whole experiment, facilitating
      visual comprehension of differences between experimental conditions. Thus, the
      presented method establishes the basis for the model-based analysis of mESC
      colony development. It can be easily extended to integrate further functional
      information using fluorescence signals and differentiation markers. AVAILABILITY:
      The analysis tool is implemented C++ and Mathematica 8.0 (Wolfram Research Inc.,
      Champaign, IL, USA). The tool is freely available from the authors. We will also
      provide the source code upon request. CONTACT: nico.scherf@tu-dresden.de.

PMID- 22962482
TI  - An approach to describing and analysing bulk biological annotation quality: a
      case study using UniProtKB.
AB  - MOTIVATION: Annotations are a key feature of many biological databases, used to
      convey our knowledge of a sequence to the reader. Ideally, annotations are
      curated manually, however manual curation is costly, time consuming and requires
      expert knowledge and training. Given these issues and the exponential increase of
      data, many databases implement automated annotation pipelines in an attempt to
      avoid un-annotated entries. Both manual and automated annotations vary in quality
      between databases and annotators, making assessment of annotation reliability
      problematic for users. The community lacks a generic measure for determining
      annotation quality and correctness, which we look at addressing within this
      article. Specifically we investigate word reuse within bulk textual annotations
      and relate this to Zipf's Principle of Least Effort. We use the UniProt
      Knowledgebase (UniProtKB) as a case study to demonstrate this approach since it
      allows us to compare annotation change, both over time and between automated and
      manually curated annotations. RESULTS: By applying power-law distributions to
      word reuse in annotation, we show clear trends in UniProtKB over time, which are
      consistent with existing studies of quality on free text English. Further, we
      show a clear distinction between manual and automated analysis and investigate
      cohorts of protein records as they mature. These results suggest that this
      approach holds distinct promise as a mechanism for judging annotation quality.
      AVAILABILITY: Source code is available at the authors website:
      http://homepages.cs.ncl.ac.uk/m.j.bell1/annotation. CONTACT:
      phillip.lord@newcastle.ac.uk.

PMID- 22962484
TI  - Event extraction across multiple levels of biological organization.
AB  - MOTIVATION: Event extraction using expressive structured representations has been
      a significant focus of recent efforts in biomedical information extraction.
      However, event extraction resources and methods have so far focused almost
      exclusively on molecular-level entities and processes, limiting their
      applicability. RESULTS: We extend the event extraction approach to biomedical
      information extraction to encompass all levels of biological organization from
      the molecular to the whole organism. We present the ontological foundations,
      target types and guidelines for entity and event annotation and introduce the new
      multi-level event extraction (MLEE) corpus, manually annotated using a structured
      representation for event extraction. We further adapt and evaluate named entity
      and event extraction methods for the new task, demonstrating that both can be
      achieved with performance broadly comparable with that for established molecular
      entity and event extraction tasks. AVAILABILITY: The resources and methods
      introduced in this study are available from http://nactem.ac.uk/MLEE/. CONTACT:
      pyysalos@cs.man.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 22962483
TI  - ReLiance: a machine learning and literature-based prioritization of receptor-
      ligand pairings.
AB  - MOTIVATION: The prediction of receptor-ligand pairings is an important area of
      research as intercellular communications are mediated by the successful
      interaction of these key proteins. As the exhaustive assaying of receptor-ligand
      pairs is impractical, a computational approach to predict pairings is necessary.
      We propose a workflow to carry out this interaction prediction task, using a text
      mining approach in conjunction with a state of the art prediction method, as well
      as a widely accessible and comprehensive dataset. Among several modern
      classifiers, random forests have been found to be the best at this prediction
      task. The training of this classifier was carried out using an experimentally
      validated dataset of Database of Ligand-Receptor Partners (DLRP) receptor-ligand
      pairs. New examples, co-cited with the training receptors and ligands, are then
      classified using the trained classifier. After applying our method, we find that
      we are able to successfully predict receptor-ligand pairs within the GPCR family
      with a balanced accuracy of 0.96. Upon further inspection, we find several
      supported interactions that were not present in the Database of Interacting
      Proteins (DIPdatabase). We have measured the balanced accuracy of our method
      resulting in high quality predictions stored in the available database ReLiance.
      AVAILABILITY: http://homes.esat.kuleuven.be/~bioiuser/ReLianceDB/index.php
      CONTACT: yves.moreau@esat.kuleuven.be; ernesto.iacucci@gmail.com SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22962485
TI  - Gene-gene interaction analysis for the survival phenotype based on the Cox model.
AB  - MOTIVATION: For the past few decades, many statistical methods in genome-wide
      association studies (GWAS) have been developed to identify SNP-SNP interactions
      for case-control studies. However, there has been less work for prospective
      cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed
      a novel method, called Surv-MDR, for detecting gene-gene interactions associated
      with survival time. Surv-MDR is an extension of the multifactor dimensionality
      reduction (MDR) method to the survival phenotype by using the log-rank test for
      defining a binary attribute. However, the Surv-MDR method has some drawbacks in
      the sense that it needs more intensive computations and does not allow for a
      covariate adjustment. In this article, we propose a new approach, called Cox-MDR,
      which is an extension of the generalized multifactor dimensionality reduction
      (GMDR) to the survival phenotype by using a martingale residual as a score to
      classify multi-level genotypes as high- and low-risk groups. The advantages of
      Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative
      covariates in the frame of Cox regression model and to require less computation
      than Surv-MDR. RESULTS: Through simulation studies, we compared the power of Cox
      MDR with those of Surv-MDR and Cox regression model for various heritability and
      minor allele frequency combinations without and with adjusting for covariate. We
      found that Cox-MDR and Cox regression model perform better than Surv-MDR for low
      minor allele frequency of 0.2, but Surv-MDR has high power for minor allele
      frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR
      and Cox regression model perform much better than Surv-MDR. We also compared the
      performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to
      detect the gene-gene interactions with the survival time. CONTACT:
      leesy@sejong.ac.kr; tspark@snu.ac.kr.

PMID- 22962486
TI  - Improving HIV coreceptor usage prediction in the clinic using hints from next
      generation sequencing data.
AB  - MOTIVATION: Due to the high mutation rate of human immunodeficiency virus (HIV),
      drug-resistant-variants emerge frequently. Therefore, researchers are constantly
      searching for new ways to attack the virus. One new class of anti-HIV drugs is
      the class of coreceptor antagonists that block cell entry by occupying a
      coreceptor on CD4 cells. This type of drug just has an effect on the subset of
      HIVs that use the inhibited coreceptor. A good prediction of whether the viral
      population inside a patient is susceptible to the treatment is hence very
      important for therapy decisions and pre-requisite to administering the respective
      drug. The first prediction models were based on data from Sanger sequencing of
      the V3 loop of HIV. Recently, a method based on next-generation sequencing (NGS)
      data was introduced that predicts labels for each read separately and decides on
      the patient label through a percentage threshold for the resistant viral
      minority. RESULTS: We model the prediction problem on the patient level taking
      the information of all reads from NGS data jointly into account. This enables us
      to improve prediction performance for NGS data, but we can also use the trained
      model to improve predictions based on Sanger sequencing data. Therefore, also
      laboratories without NGS capabilities can benefit from the improvements.
      Furthermore, we show which amino acids at which position are important for
      prediction success, giving clues on how the interaction mechanism between the V3
      loop and the particular coreceptors might be influenced. AVAILABILITY: A
      webserver is available at http://coreceptor.bioinf.mpi-inf.mpg.de. CONTACT:
      nico.pfeifer@mpi-inf.mpg.de.

PMID- 22962487
TI  - An accurate paired sample test for count data.
AB  - MOTIVATION: Recent technology platforms in proteomics and genomics produce count
      data for quantitative analysis. Previous works on statistical significance
      analysis for count data have mainly focused on the independent sample setting,
      which does not cover the case where pairs of measurements are taken from
      individual patients before and after treatment. This experimental setting
      requires paired sample testing such as the paired t-test often used for
      continuous measurements. A state-of-the-art method uses a negative binomial
      distribution in a generalized linear model framework for paired sample testing. A
      paired sample design assumes that the relative change within each pair is
      constant across biological samples. This model can be used as an approximation to
      the true model in cases of heterogeneity of response in complex biological
      systems. We aim to specify the variation in response explicitly in combination
      with the inherent technical variation. RESULTS: We formulate the problem of
      paired sample test for count data in a framework of statistical combination of
      multiple contingency tables. In particular, we specify explicitly a random
      distribution for the effect with an inverted beta model. The technical variation
      can be modeled by either a standard Poisson distribution or an exponentiated
      Poisson distribution, depending on the reproducibility of the acquisition
      workflow. The new statistical test is evaluated on both proteomics and genomics
      datasets, showing a comparable performance to the state-of-the-art method in
      general, and in several cases where the two methods differ, the proposed test
      returns more reasonable p-values. AVAILABILITY: Available for download at
      http://www.oncoproteomics.nl/. CONTACT: t.pham@vumc.nl.

PMID- 22962488
TI  - Bayesian assignment of gene ontology terms to gene expression experiments.
AB  - MOTIVATION: Gene expression assays allow for genome scale analyses of molecular
      biological mechanisms. State-of-the-art data analysis provides lists of involved
      genes, either by calculating significance levels of mRNA abundance or by Bayesian
      assessments of gene activity. A common problem of such approaches is the
      difficulty of interpreting the biological implication of the resulting gene
      lists. This lead to an increased interest in methods for inferring high-level
      biological information. A common approach for representing high level information
      is by inferring gene ontology (GO) terms which may be attributed to the
      expression data experiment. RESULTS: This article proposes a probabilistic model
      for GO term inference. Modelling assumes that gene annotations to GO terms are
      available and gene involvement in an experiment is represented by a posterior
      probabilities over gene-specific indicator variables. Such probability measures
      result from many Bayesian approaches for expression data analysis. The proposed
      model combines these indicator probabilities in a probabilistic fashion and
      provides a probabilistic GO term assignment as a result. Experiments on synthetic
      and microarray data suggest that advantages of the proposed probabilistic GO term
      inference over statistical test-based approaches are in particular evident for
      sparsely annotated GO terms and in situations of large uncertainty about gene
      activity. Provided that appropriate annotations exist, the proposed approach is
      easily applied to inferring other high level assignments like pathways.
      AVAILABILITY: Source code under GPL license is available from the author.
      CONTACT: peter.sykacek@boku.ac.at.

PMID- 22962489
TI  - Drug target prediction using adverse event report systems: a pharmacogenomic
      approach.
AB  - MOTIVATION: Unexpected drug activities derived from off-targets are usually
      undesired and harmful; however, they can occasionally be beneficial for different
      therapeutic indications. There are many uncharacterized drugs whose target
      proteins (including the primary target and off-targets) remain unknown. The
      identification of all potential drug targets has become an important issue in
      drug repositioning to reuse known drugs for new therapeutic indications. RESULTS:
      We defined pharmacological similarity for all possible drugs using the US Food
      and Drug Administration's (FDA's) adverse event reporting system (AERS) and
      developed a new method to predict unknown drug-target interactions on a large
      scale from the integration of pharmacological similarity of drugs and genomic
      sequence similarity of target proteins in the framework of a pharmacogenomic
      approach. The proposed method was applicable to a large number of drugs and it
      was useful especially for predicting unknown drug-target interactions that could
      not be expected from drug chemical structures. We made a comprehensive prediction
      for potential off-targets of 1874 drugs with known targets and potential target
      profiles of 2519 drugs without known targets, which suggests many potential drug
      target interactions that were not predicted by previous chemogenomic or
      pharmacogenomic approaches. AVAILABILITY: Softwares are available upon request.
      CONTACT: yamanishi@bioreg.kyushu-u.ac.jp SUPPLEMENTARY INFORMATION: Datasets and
      all results are available at http://cbio.ensmp.fr/~yyamanishi/aers/.

PMID- 22962490
TI  - From phenotype to genotype: an association study of longitudinal phenotypic
      markers to Alzheimer's disease relevant SNPs.
AB  - MOTIVATION: Imaging genetic studies typically focus on identifying single
      nucleotide polymorphism (SNP) markers associated with imaging phenotypes. Few
      studies perform regression of SNP values on phenotypic measures for examining how
      the SNP values change when phenotypic measures are varied. This alternative
      approach may have a potential to help us discover important imaging genetic
      associations from a different perspective. In addition, the imaging markers are
      often measured over time, and this longitudinal profile may provide increased
      power for differentiating genotype groups. How to identify the longitudinal
      phenotypic markers associated to disease sensitive SNPs is an important and
      challenging research topic. RESULTS: Taking into account the temporal structure
      of the longitudinal imaging data and the interrelatedness among the SNPs, we
      propose a novel 'task-correlated longitudinal sparse regression' model to study
      the association between the phenotypic imaging markers and the genotypes encoded
      by SNPs. In our new association model, we extend the widely used l(2,1)-norm for
      matrices to tensors to jointly select imaging markers that have common effects
      across all the regression tasks and time points, and meanwhile impose the trace
      norm regularization onto the unfolded coefficient tensor to achieve low rank such
      that the interrelationship among SNPs can be addressed. The effectiveness of our
      method is demonstrated by both clearly improved prediction performance in
      empirical evaluations and a compact set of selected imaging predictors relevant
      to disease sensitive SNPs. AVAILABILITY: Software is publicly available at:
      http://ranger.uta.edu/%7eheng/Longitudinal/ CONTACT: heng@uta.edu or
      shenli@inpui.edu.

PMID- 22962491
TI  - A novel approach for resolving differences in single-cell gene expression
      patterns from zygote to blastocyst.
AB  - MOTIVATION: Single-cell experiments of cells from the early mouse embryo yield
      gene expression data for different developmental stages from zygote to
      blastocyst. To better understand cell fate decisions during differentiation, it
      is desirable to analyse the high-dimensional gene expression data and assess
      differences in gene expression patterns between different developmental stages as
      well as within developmental stages. Conventional methods include univariate
      analyses of distributions of genes at different stages or multivariate linear
      methods such as principal component analysis (PCA). However, these approaches
      often fail to resolve important differences as each lineage has a unique gene
      expression pattern which changes gradually over time yielding different gene
      expressions both between different developmental stages as well as heterogeneous
      distributions at a specific stage. Furthermore, to date, no approach taking the
      temporal structure of the data into account has been presented. RESULTS: We
      present a novel framework based on Gaussian process latent variable models
      (GPLVMs) to analyse single-cell qPCR expression data of 48 genes from mouse
      zygote to blastocyst as presented by (Guo et al., 2010). We extend GPLVMs by
      introducing gene relevance maps and gradient plots to provide interpretability as
      in the linear case. Furthermore, we take the temporal group structure of the data
      into account and introduce a new factor in the GPLVM likelihood which ensures
      that small distances are preserved for cells from the same developmental stage.
      Using our novel framework, it is possible to resolve differences in gene
      expressions for all developmental stages. Furthermore, a new subpopulation of
      cells within the 16-cell stage is identified which is significantly more
      trophectoderm-like than the rest of the population. The trophectoderm-like
      subpopulation was characterized by considerable differences in the expression of
      Id2, Gata4 and, to a smaller extent, Klf4 and Hand1. The relevance of Id2 as
      early markers for TE cells is consistent with previously published results.
      AVAILABILITY: The mappings were implemented based on Prof. Neil Lawrence's FGPLVM
      toolbox(1); extensions for relevance analysis and including the structure of the
      data can be obtained from one of the authors' homepage.(2) CONTACT:
      f.buettner@helmholtz-muenchen.de.

PMID- 22962492
TI  - Finding differentially expressed regions of arbitrary length in quantitative
      genomic data based on marked point process model.
AB  - MOTIVATION: High-throughput nucleotide sequencing technologies provide large
      amounts of quantitative genomic data at nucleotide resolution, which are
      important for the present and future biomedical researches; for example
      differential analysis of base-level RNA expression data will improve our
      understanding of transcriptome, including both coding and non-coding genes.
      However, most studies of these data have relied on existing genome annotations
      and thus are limited to the analysis of known transcripts. RESULTS: In this
      article, we propose a novel method based on a marked point process model to find
      differentially expressed genomic regions of arbitrary length without using genome
      annotations. The presented method conducts a statistical test for differential
      analysis in regions of various lengths at each nucleotide and searches the
      optimal configuration of the regions by using a Monte Carlo simulation. We
      applied the proposed method to both synthetic and real genomic data, and their
      results demonstrate the effectiveness of our method. AVAILABILITY: The program
      used in this study is available at https://sites.google.com/site/hiroshihatsuda/.
      CONTACT: H.Hatsuda@warwick.ac.uk.

PMID- 22962493
TI  - PARADIGM-SHIFT predicts the function of mutations in multiple cancers using
      pathway impact analysis.
AB  - MOTIVATION: A current challenge in understanding cancer processes is to pinpoint
      which mutations influence the onset and progression of disease. Toward this goal,
      we describe a method called PARADIGM-SHIFT that can predict whether a mutational
      event is neutral, gain-or loss-of-function in a tumor sample. The method uses a
      belief-propagation algorithm to infer gene activity from gene expression and copy
      number data in the context of a set of pathway interactions. RESULTS: The method
      was found to be both sensitive and specific on a set of positive and negative
      controls for multiple cancers for which pathway information was available.
      Application to the Cancer Genome Atlas glioblastoma, ovarian and lung squamous
      cancer datasets revealed several novel mutations with predicted high impact
      including several genes mutated at low frequency suggesting the approach will be
      complementary to current approaches that rely on the prevalence of events to
      reach statistical significance. AVAILABILITY: All source code is available at the
      github repository http:github.org/paradigmshift. CONTACT: jstuart@soe.ucsc.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22962496
TI  - U.S. Migration, Translocality, and the Acceleration of the Nutrition Transition
      in Mexico.
AB  - Migrant flows are generally accompanied by extensive social, economic, and
      cultural links between origins and destinations, transforming the former's
      community life, livelihoods, and local practices. Previous studies have found a
      positive association between these translocal ties and better child health and
      nutrition. We contend that focusing on children only provides a partial view of a
      larger process affecting community health, accelerating the nutrition transition
      in particular. We use a Mexican nationally-representative survey with
      socioeconomic, anthropometric, and biomarker measures, matched to municipal-level
      migration intensity and marginalization measures from the Mexican 2000 Census to
      study the association between adult body mass and community migration intensity.
      Our findings from multi-level models suggest a significant and positive
      relationship between community-level migration intensity and the individual risk
      of being overweight and obese, with significant differences by gender and with
      remittance intensity playing a preponderant role.

PMID- 22962497
TI  - Rarefaction and blood pressure in systemic and pulmonary arteries.
AB  - The effects of vascular rarefaction (the loss of small arteries) on the
      circulation of blood are studied using a multiscale mathematical model that can
      predict blood flow and pressure in the systemic and pulmonary arteries. We
      augmented a model originally developed for the systemic arteries (Olufsen et al.
      1998, 1999, 2000, 2004) to (a) predict flow and pressure in the pulmonary
      arteries, and (b) predict pressure propagation along the small arteries in the
      vascular beds. The systemic and pulmonary arteries are modelled as separate,
      bifurcating trees of compliant and tapering vessels. Each tree is divided into
      two parts representing the 'large' and 'small' arteries. Blood flow and pressure
      in the large arteries are predicted using a nonlinear cross-sectional area
      averaged model for a Newtonian fluid in an elastic tube with inflow obtained from
      magnetic resonance measurements. Each terminal vessel within the network of the
      large arteries is coupled to a vascular bed of small 'resistance' arteries, which
      are modelled as asymmetric structured trees with specified area and asymmetry
      ratios between the parent and daughter arteries. For the systemic circulation,
      each structured tree represents a specific vascular bed corresponding to major
      organs and limbs. For the pulmonary circulation, there are four vascular beds
      supplied by the interlobar arteries. This manuscript presents the first
      theoretical calculations of the propagation of the pressure and flow waves along
      systemic and pulmonary large and small arteries. Results for all networks were in
      agreement with published observations. Two studies were done with this model.
      First, we showed how rarefaction can be modelled by pruning the tree of arteries
      in the microvascular system. This was done by modulating parameters used for
      designing the structured trees. Results showed that rarefaction leads to
      increased mean and decreased pulse pressure in the large arteries. Second, we
      investigated the impact of decreasing vessel compliance in both large and small
      arteries. Results showed, that the effects of decreased compliance in the large
      arteries far outweigh the effects observed when decreasing the compliance of the
      small arteries. We further showed that a decrease of compliance in the large
      arteries results in pressure increases consistent with observations of isolated
      systolic hypertension, as occurs in ageing.

PMID- 22962498
TI  - Marriage Expectations Among African American Couples in Early Adulthood: A Dyadic
      Analysis.
AB  - Using Family and Community Health Study data consisting of 168 unmarried,
      primarily African American couples, the current study sought to understand the
      dyadic interplay among school, work, and partner-specific marriage expectations
      in early adulthood. Drawing on the economic prospects, adult transitions, and
      work - family literatures, the authors hypothesized and found ample support that
      expectations to marry a romantic partner were linked not only to one's own school
      and work-related experiences but also to those of a partner. These associations
      held while controlling for relationship satisfaction, general views of marriage,
      and other covariates that have been posited to explain racial inequalities in
      relationship and marriage patterns. Furthermore, the authors found that actor
      covariates of marital expectations differed from partner covariates, a finding
      that highlights the advantages of dyadic analyses in helping researchers
      understand marriage as both a developmental and interpersonal process.

PMID- 22962499
TI  - Signal identification for rare and weak features: higher criticism or false
      discovery rates?
AB  - Signal identification in large-dimensional settings is a challenging problem in
      biostatistics. Recently, the method of higher criticism (HC) was shown to be an
      effective means for determining appropriate decision thresholds. Here, we study
      HC from a false discovery rate (FDR) perspective. We show that the HC threshold
      may be viewed as an approximation to a natural class boundary (CB) in two-class
      discriminant analysis which in turn is expressible as the FDR threshold. We
      demonstrate that in a rare-weak setting in the region of the phase space where
      signal identification is possible, both thresholds are practicably
      indistinguishable, and thus HC thresholding is identical to using a simple local
      FDR cutoff. The relationship of the HC and CB thresholds and their properties are
      investigated both analytically and by simulations, and are further compared by
      the application to four cancer gene expression data sets.

PMID- 22962500
TI  - Lessons Learned while Traversing the Welwitindolinone Alkaloids Obstacle Course.
AB  - We recount several unexpected results observed in the course of our work toward
      the synthesis of welwitindolinone alkaloids. The surprising results provide an
      opportunity to refine one's understanding of the interplay between chemical
      structure and reactivity.

PMID- 22962501
TI  - Concise Approach to 1,4-Dioxygenated Xanthones via Novel Application of the Moore
      Rearrangement.
AB  - The rapid synthesis of 1,4-dioxygenated xanthones and related natural products
      employing the Moore rearrangement as a key transformation has been developed. The
      approach features an acetylide stitching step to unite a substituted squaric acid
      with a protected hydroxy benzaldehyde derivative to provide a key intermediate
      that undergoes facile Moore rearrangement to deliver a hydroxymethyl aryl
      quinone. Subsequent oxidation, hydroxy group deprotection and cyclization then
      affords highly functionalized xanthones. The utility of the approach was
      demonstrated by its application to a concise and efficient synthesis of the
      naturally-occurring xanthone 1. The structure of a natural product that had been
      named dulcisxanthone C was also corrected to that of the xanthone 1.

PMID- 22962502
TI  - Selective Structural Transformation of Supramolecules to Multinuclear
      Heterosubstituted Pt Complexes via Ligand Exchange.
AB  - Selective triflate to chlorine ligand exchange reaction between ditriflate and
      dichloride Pt complexes producing pure heterosubstituted complexes is
      demonstrated. We show that this reaction can be applied for selective
      chlorination of supramolecules leading to their structural transformation into
      multinuclear mono-chlorinated Pt(II) complexes. The X-ray structure of complex of
      4,4'-bipyridine with two molecules of (Et(3)P)(2)Pt(Cl)OTf is reported.

PMID- 22962503
TI  - SYNTHESIS OF (+)-B-ALLYLDIISOPINOCAMPHEYLBORANE AND ITS REACTION WITH ALDEHYDES.

PMID- 22962504
TI  - Image mapping spectrometry: calibration and characterization.
AB  - Image mapping spectrometry (IMS) is a hyperspectral imaging technique that
      simultaneously captures spatial and spectral information about an object in real
      time. We present a new calibration procedure for the IMS as well as the first
      detailed evaluation of system performance. We correlate optical components and
      device calibration to performance metrics such as light throughput, scattered
      light, distortion, spectral image coregistration, and spatial/spectral
      resolution. Spectral sensitivity and motion artifacts are also evaluated with a
      dynamic biological experiment. The presented methodology of evaluation is useful
      in assessment of a variety of hyperspectral and multi-spectral modalities.
      Results are important to any potential users/developers of an IMS instrument and
      to anyone who may wish to compare the IMS to other imaging spectrometers.

PMID- 22962505
TI  - Personality as a Source of Individual Differences in Cognition among Older
      African Americans.
AB  - Previous research suggests that demographic factors are important correlates of
      cognitive functioning in African Americans; however, less attention has been
      given to the influence of personality. The present study explored how dimensions
      and facets of personality predicted individual variability in cognition in a
      sample of older African Americans from the Baltimore Study of Black Aging.
      Cognition was assessed by verbal learning and attention/working memory measures.
      Personality was measured by the NEO Personality Inventory. Linear regressions
      controlling for demographic factors showed that Neuroticism, Openness, and
      Agreeableness were significant regression predictors of cognitive performance.
      Individual facets of all five personality dimensions were also associated with
      cognitive performance. These findings suggest personality is important in
      understanding variability in cognition among older African Americans.

PMID- 22962506
TI  - Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster
      Children's HPA Axis Reactivity During a Psychosocial Stressor.
AB  - Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has
      been reported among individuals with prenatal substance exposure and those with
      early adversity. However, few researchers have examined the combined effects of
      these risk factors. Patterns of HPA reactivity among maltreated foster children
      with and without prenatal substance exposure (N = 53; ages 9-12 years) were
      examined using the Trier Social Stress Test for Children. Area under the curve
      with respect to increase (AUC(I)) analyses revealed that prenatal substance
      exposure or physical abuse significantly increased the likelihood of a negative
      AUC(I) (i.e., little or no HPA reactivity). Among children with prenatal
      substance exposure and physical abuse, 85% exhibited a negative AUC(I). The
      results underscore the importance of addressing this combined risk.

PMID- 22962507
TI  - A Sudden Transition: Household Changes for Middle Aged U.S. Women in the
      Twentieth Century.
AB  - Between 1900 and 1990, the percentage of U.S. white women aged 40-69 living with
      a child of their own fell from 63% to 27%, with three fourths of that change
      occurring between 1940 and 1960. Historical census data from the Integrated
      Public Use Microdata Series and longitudinal data from the Panel Study of Income
      Dynamics allow an historical and contemporary examination of co-residence
      patterns among these women. Analysis reveals three eras: a system of co-residence
      in the early twentieth century, a sudden transition toward separate households at
      mid century, and the maintenance of that separate household system thereafter.
      The scholarly literature features cultural, demographic, and economic
      explanations for the long-term decline in co-residence, but has given little
      attention to the rapid mid-century shift. Analysis of IPUMS data confirms the
      long-term effects of declines in mortality and fertility, and concomitant
      declines in the age of mothers at last birth, but also points to a sharp drop in
      the age of children at marriage in the mid-twentieth century. These factors
      raised the potential for the formation of separate households, but this
      historical era was also a propitious one for separation: income gains for young
      workers were unprecedented, the labor force participation of married women rose,
      and immigration fell. Analysis of PSID data from 1968 to 2009 confirms the
      salience of children's socioeconomic circumstances-particularly their marriage
      and employment prospects but also the increasing availability of higher education
      in maintaining the separate household system. While the data analyzed allow only
      inferences about cultural factors, the resiliency of the new household system,
      even in periods of economic decline, suggests that it is now likely buttressed by
      strong normative views.

PMID- 22962508
TI  - Agricultural settlement and soil quality in the Brazilian Amazon.
AB  - This paper discusses the implications of poor or non-existent information on soil
      quality, at the proper scale, during the planning and implementation of
      settlement projects in the Brazilian Amazon. Based on data from the Machadinho
      settlement project, Rondonia, we show that most settlers had no knowledge about
      the agricultural capability of the area, did not receive technical information,
      could not afford agricultural inputs, planted inadequate crops in the early years
      of occupation, and did not manage to stay in their plot for a long period of
      time. Satellite images indicated that patches of land with good soil quality were
      not necessarily the first to be utilized. Inadequately planned settlements face
      many challenges (poor soil being one of them) and are likely to result in land
      turnover, conversion of land into pasture, land concentration among wealthier
      persons, invasion of areas by poorer people, and deforestation, defying the main
      purpose of agrarian reform.

PMID- 22962509
TI  - Considering a multi-level approach to understanding maintenance of global
      coherence in adults with aphasia.
AB  - BACKGROUND: Discourse is a naturally occurring, dynamic form of communication.
      Coherence is one aspect of discourse and is a reflection of the listener's
      ability to interpret the overall meaning conveyed by the speaker. Adults with
      aphasia may present with impaired maintenance of global coherence, which, in
      turn, may contribute to their difficulties in overall communicative competence. 
      AIMS: The aim of the study was to determine if microlinguistic processes
      contribute to maintenance of global coherence in adults with and without aphasia.
      METHOD AND PROCEDURES: Participants included 15 adults with aphasia (PWA) and 15
      healthy controls (HC). Study participants told stories conveyed in wordless
      picture books. The discourse samples were transcribed and then analyzed for
      percent of information units produced, lexical diversity, syntactic complexity,
      and maintenance of global coherence.  OUTCOMES AND RESULTS: Several linear
      regression models were carried out to investigate the relationship among the
      microlinguistic and macrolinguistic measures. For the control group, percent of
      information units conveyed was a significant predictor of maintenance of global
      coherence for stories told. For the aphasia group, percent of information units
      conveyed and lexical diversity were significant predictors of maintenance of
      global coherence for stories told.  CONCLUSIONS: Results indicated that
      microlinguistic processes contribute to the maintenance of global coherence in
      stories told by adults with aphasia. These findings have important clinical
      implications for using a multi-level discourse model for analyzing discourse
      ability in adults with aphasia and measuring individual response to treatment.

PMID- 22962510
TI  - Maternal exposure to predation risk decreases offspring antipredator behaviour
      and survival in threespined stickleback.
AB  - 1. Adaptive maternal programming occurs when mothers alter their offspring's
      phenotype in response to environmental information such that it improves
      offspring fitness. When a mother's environment is predictive of the conditions
      her offspring are likely to encounter, such transgenerational plasticity enables
      offspring to be better-prepared for this particular environment. However,
      maternal effects can also have deleterious effects on fitness.2. Here, we test
      whether female threespined stickleback fish exposed to predation risk adaptively
      prepare their offspring to cope with predators. We either exposed gravid females
      to a model predator or not, and compared their offspring's antipredator behaviour
      and survival when alone with a live predator. Importantly, we measured offspring
      behaviour and survival in the face of the same type of predator that threatened
      their mothers (Northern pike).3. We did not find evidence for adaptive maternal
      programming; offspring of predator-exposed mothers were less likely to orient to
      the predator than offspring from unexposed mothers. In our predation assay,
      orienting to the predator was an effective antipredator behaviour and those that
      oriented, survived for longer.4. In addition, offspring from predator-exposed
      mothers were caught more quickly by the predator on average than offspring from
      unexposed mothers. The difference in antipredator behaviour between the maternal
      predator-exposure treatments offers a potential behavioural mechanism
      contributing to the difference in survival between maternal treatments.5.
      However, the strength and direction of the maternal effect on offspring survival
      depended on offspring size. Specifically, the larger the offspring from predator
      exposed mothers, the more vulnerable they were to predation compared to offspring
      from unexposed mothers.6. Our results suggest that the predation risk perceived
      by mothers can have long-term behavioural and fitness consequences for offspring
      in response to the same predator. These stress-mediated maternal effects can have
      nonadaptive consequences for offspring when they find themselves alone with a
      predator. In addition, complex interactions between such maternal effects and
      offspring traits such as size can influence our conclusions about the adaptive
      nature of maternal effects.

PMID- 22962512
TI  - Educational Inequalities among Latin American Adolescents: Continuities and
      Changes over the 1980s, 1990s and 2000s.
AB  - The goal of this paper is to examine recent trends in educational stratification
      for Latin American adolescents growing up in three distinct periods: the 1980s,
      during severe recession; the 1990s, a period of structural adjustments imposed by
      international organizations; and the late 2000s, when most countries in the
      region experienced positive and stable growth. In addition to school enrollment
      and educational transitions, we examine the quality of education through
      enrollment in private schools, an important aspect of inequality in education
      that most studies have neglected. We use nationally representative household
      survey data for the 1980s, 1990s and 2000s in Brazil, Chile, Mexico and Uruguay.
      Our overall findings confirm the importance of macroeconomic conditions for
      inequalities in educational opportunity, suggesting important benefits brought up
      by the favorable conditions of the 2000s. However, our findings also call
      attention to increasing disadvantages associated with the quality of the
      education adolescents receive, suggesting the significance of the EMI framework
      Effectively Maintained Inequality-and highlighting the value of examining the
      quality in addition to the quantity of education in order to fully understand
      educational stratification in the Latin American context.

PMID- 22962511
TI  - Structure Activity Relationships for Derivatives of Adenosine-5'-Triphosphate as
      Agonists at P(2) Purinoceptors: Heterogeneity Within P(2X) and P(2Y) Subtypes.
AB  - The structure-activity relationships for a variety of adenine nucleotide
      analogues at P(2x)- and P(2Y)-purinoceptors were investigated. Compounds formed
      by structural modifications of the ATP molecule including substitutions of the
      purine ring (C2, C8, N1, and N(6)-substituents, and a uridine base instead of
      adenine), the ribose moiety (2' and 3'-positions), and the triphosphate group
      (lower phosphates, bridging oxygen substitution, and cyclization) were prepared.
      Pharmacological activity at P(2Y)-purinoceptors was assayed in the guinea pig
      taenia coli, endothelial cells of the rabbit aorta, smooth muscle of the rabbit
      mesenteric artery, and turkey erythrocyte membranes. Activity at P(2X)
      purinoceptors was assayed in the rabbit saphenous artery and the guinea-pig vas
      deferens and urinary bladder. Some of the analogues displayed selectivity, or
      even specificity, for either the P(2X)- or the P(2Y)-purinoceptors. Certain
      analogues displayed selectivity or specificity within the P(2X)- or P(2Y)
      purinoceptor superfamilies, giving hints about possible subclasses. For example,
      8-(6-aminohexylamino)ATP and 2',3'-isopropylidene-AMP were selective for
      endothelial Pzypurinoceptors over P(2Y)-purinoceptors in the guinea pig taenia
      coli, rabbit aorta, and turkey erythrocytes. These compounds were both inactive
      at P(2X)-purinoceptors. The potent agonist N(6)-methyl ATP and the somewhat less
      potent agonist 2'-deoxy-ATP were selective for P(2Y)-purinoceptors in the guinea
      pig taenia coli, but were inactive at P(2X)-purinoceptors and the vascular P(2Y)
      purinoceptors. 3'-Benzylamino-3'-deoxyATP was very potent at the P(2X)
      purinoceptors in the guinea pig vas deferens and bladder, but not in the rabbit
      saphenous artery and was inactive at P(2Y) receptors. These data suggest that
      specific compounds can be developed that can be utilized to activate putative
      subtypes of the P(2X)- and P(2Y)-purinoceptor classes.

PMID- 22962513
TI  - Reaction of Aryl Diazonium Salts and Diiron(I) Dithiolato Carbonyls: Evidence for
      Radical Intermediates.
AB  - Treatment of Fe(2)(pdt)(CO)(4)(dppv) (1) with aryldiazonium salts affords the
      34e(-) adducts [Fe(2)(pdt)(MU-N(2)Ar)(CO)(4)(dppv)](+) (pdt(2-) = 1,3
      propanedithiolate, dppv = cis-C(2)H(2)(PPh(2))(2)). Under some conditions, the
      same reaction gave substantial amounts of [1](+), the product of electron
      transfer. Consistent with the influence of electron transfer in the reactions of
      some electrophiles with Fe(I)Fe(I) dithiolates, the reaction of [Me(3)S(2)](+)
      and Fe(2)(pdt)(CO)(4)(dppbz) was found to give [Fe(2)(pdt)(CO)(4)(dppbz)](+) as
      well as Me(2)S and Me(2)S(2) (dppbz = 1,2-bis(diphenylphosphino)benzene).

PMID- 22962514
TI  - Wars and Child Health: Evidence from the Eritrean-Ethiopian Conflict.
AB  - Conflict between and within countries can have lasting health and economic
      consequences, but identifying such effects can be empirically challenging. This
      paper uses household survey data from Eritrea to estimate the effect of exposure
      to the 1998-2000 Eritrea-Ethiopia war on children's health. The identification
      strategy exploits exogenous variation in the conflict's geographic extent and
      timing and the exposure of different birth cohorts to the fighting. The unique
      survey data include details on each household's migration history, which allows
      us to measure a child's geographic location during the war and without which war
      exposure would be incorrectly classified. War-exposed children have lower height
      for-age Z-scores, with similar effects for children born before or during the
      war. Both boys and girls who are born during the war experience negative impacts
      due to conflict. Effects are robust to including region-specific time trends,
      alternative conflict exposure measures, and mother fixed effects.

PMID- 22962515
TI  - Simultaneous, single particle, magnetization and size measurements of micron
      sized, magnetic particles.
AB  - Single particle magnetization and size measurements of micron and nano sized,
      magnetic particles were made using a previously described device referred to as
      Cell Tracking Velocimetry, CTV. Three types of commercially available, and
      commonly used, magnetic particles were studied in this report. While the CTV
      instrument provides individual particles measurements, the average magnetization
      and size measurements were found to have reasonable agreements with reported
      values from instruments which measure bulk values. In addition, the CTV
      instrument, using electromagnets, can also determine magnetization curves, which
      also proved to have reasonable agreement with other published studies. Given that
      magnetic separation and analysis technology is dependent on the quality of the
      magnetic particles used, studies such as this one using CTV provide not only
      average data, but also provides information with respect to the distribution of
      the properties such as magnetization and size. For example, the spread of the
      data in magnetic and settling velocities were found to be predominately due to
      the size distribution of the analyzed particles.

PMID- 22962516
TI  - Crying in Middle Childhood: A Report on Gender Differences.
AB  - The aims of this study were (1) to confirm gender differences in crying in middle
      childhood and (2) to identify factors that may explain why girls cry more than
      boys in a Dutch sample (North Holland and Utrecht). We examined 186 children's
      (age: 9-13 years) self-reports on crying, catharsis, seeking support for
      feelings, and internalizing feelings. Girls reported a greater crying frequency
      and crying proneness, and more emotional and physical catharsis after crying. In
      addition, they more frequently sought support for feelings and more often
      experienced sadness and somatic complaints than boys. Seeking help for negative
      feelings and the experience of sadness and somatic complaints were positively
      associated with crying frequency and crying proneness. Emotional catharsis was
      positively linked to crying proneness. Support was found for the potential
      mediating role of sadness and somatic complaints with respect to the gender
      difference in crying frequency and for the potential mediating role of emotional
      catharsis and somatic complaints for crying proneness. This study demonstrates
      that gender differences in crying frequency already exist in middle childhood and
      the findings suggest a linkage between these gender differences in crying and
      psychosocial factors.

PMID- 22962517
TI  - Immobilized Carbonic Anhydrase on Hollow Fiber Membranes Accelerates CO(2)
      Removal from Blood.
AB  - Current artificial lungs and respiratory assist devices designed for carbon
      dioxide removal (CO(2)R) are limited in their efficiency due to the relatively
      small partial pressure difference across gas exchange membranes. To offset this
      underlying diffusional challenge, bioactive hollow fiber membranes (HFMs)
      increase the carbon dioxide diffusional gradient through the immobilized enzyme
      carbonic anhydrase (CA), which converts bicarbonate to CO(2) directly at the HFM
      surface. In this study, we tested the impact of CA-immobilization on HFM CO(2)
      removal efficiency and thromboresistance in blood. Fiber surface modification
      with radio frequency glow discharge (RFGD) introduced hydroxyl groups, which were
      activated by 1M CNBr while 1.5M TEA was added drop wise over the activation time
      course, then incubation with a CA solution covalently linked the enzyme to the
      surface. The bioactive HFMs were then potted in a model gas exchange device
      (0.0084 m(2)) and tested in a recirculation loop with a CO(2) inlet of 50mmHg
      under steady blood flow. Using an esterase activity assay, CNBr chemistry with
      TEA resulted in 0.99U of enzyme activity, a 3.3 fold increase in immobilized CA
      activity compared to our previous method. These bioactive HFMs demonstrated 108
      ml/min/m(2) CO(2) removal rate, marking a 36% increase compared to unmodified
      HFMs (p < 0.001). Thromboresistance of CA-modified HFMs was assessed in terms of
      adherent platelets on surfaces by using lactate dehydrogenase (LDH) assay as well
      as scanning electron microscopy (SEM) analysis. Results indicated HFMs with CA
      modification had 95% less platelet deposition compared to unmodified HFM (p <
      0.01). Overall these findings revealed increased CO(2) removal can be realized
      through bioactive HFMs, enabling a next generation of more efficient CO(2)
      removal intravascular and paracorporeal respiratory assist devices.

PMID- 22962518
TI  - A note on confidence bounds after fixed-sequence multiple tests.
AB  - We are concerned with the problem of estimating the treatment effects at the
      effective doses in a dose-finding study. Under monotone dose-response, the
      effective doses can be identified through the estimation of the minimum effective
      dose, for which there is an extensive set of statistical tools. In particular,
      when a fixed-sequence multiple testing procedure is used to estimate the minimum
      effective dose, Hsu and Berger (1999) show that the confidence lower bounds for
      the treatment effects can be constructed without the need to adjust for
      multiplicity. Their method, called the dose-response method, is simple to use,
      but does not account for the magnitude of the observed treatment effects. As a
      result, the dose-response method will estimate the treatment effects at effective
      doses with confidence bounds invariably identical to the hypothesized value. In
      this paper, we propose an error-splitting method as a variant of the dose
      response method to construct confidence bounds at the identified effective doses
      after a fixed-sequence multiple testing procedure. Our proposed method has the
      virtue of simplicity as in the dose-response method, preserves the nominal
      coverage probability, and provides sharper bounds than the dose-response method
      in most cases.

PMID- 22962519
TI  - Reducing Bias and Mean Squared Error Associated With Regression-Based Odds Ratio
      Estimators.
AB  - Ratio estimators of effect are ordinarily obtained by exponentiating maximum
      likelihood estimators (MLEs) of log-linear or logistic regression coefficients.
      These estimators can display marked positive finite-sample bias, however. We
      propose a simple correction that removes a substantial portion of the bias due to
      exponentiation. By combining this correction with bias correction on the log
      scale, we demonstrate that one achieves complete removal of second-order bias in
      odds ratio estimators in important special cases. We show how this approach
      extends to address bias in odds or risk ratio estimators in many common
      regression settings. We also propose a class of estimators that provide reduced
      mean bias and squared error, while allowing the investigator to control the risk
      of underestimating the true ratio parameter. We present simulation studies in
      which the proposed estimators are shown to exhibit considerable reduction in
      bias, variance, and mean squared error compared to MLEs. Bootstrapping provides
      further improvement, including narrower confidence intervals without sacrificing
      coverage.

PMID- 22962520
TI  - Improving Parolees' Participation in Drug Treatment and Other Services through
      Strengths Case Management.
AB  - In an effort to increase participation in community aftercare treatment for
      substance-abusing parolees, an intervention based on a transitional case
      management (TCM) model that focuses mainly on offenders' strengths has been
      developed and is under testing. This model consists of completion, by the inmate,
      of a self-assessment of strengths that informs the development of the continuing
      care plan, a case conference call shortly before release, and strengths case
      management for three months post-release to promote retention in substance abuse
      treatment and support the participant's access to designated services in the
      community. The post-release component consists of a minimum of one weekly
      client/case manager meeting (in person or by telephone) for 12 weeks. The
      intervention is intended to improve the transition process from prison to
      community at both the individual and systems level. Specifically, the
      intervention is designed to improve outcomes in parolee admission to, and
      retention in, community-based substance-abuse treatment, parolee access to other
      needed services, and recidivism rates during the first year of parole. On the
      systems level, the intervention is intended to improve the communication and
      collaboration between criminal justice agencies, community-based treatment
      organizations, and other social and governmental service providers. The TCM model
      is being tested in a multisite study through the Criminal Justice Drug Abuse
      Treatment Studies (CJ-DATS) research cooperative funded by the National Institute
      of Drug Abuse.

PMID- 22962521
TI  - African American Caregivers and Substance Abuse in Child Welfare: Identification
      of Multiple Risk Profiles.
AB  - Despite the strong correlation between caregiver substance abuse and child
      maltreatment, little information exists to understand the typology of African
      American caregivers with substance abuse problems in the child welfare system.
      Research shows African American caregivers contend with multiple problems
      stemming from substance abuse. Unfortunately, we do not yet know how to best
      tailor resources to be responsive to varying groups of African American
      caregivers. Using data from the National Survey of Child and Adolescent Well
      being (NSCAW), this investigation tested for distinct multivariate profiles among
      a subset of African American caregivers with substance abuse problems (n=258).
      Latent Class Analysis (LCA) was used to classify caregivers, and five classes
      were identified among this high risk sample - each with distinct risk profiles.
      Based on these findings, we discuss implications for tailored practices to
      enhance the safety and stability of children involved with child welfare.

PMID- 22962522
TI  - Revaprazan, a novel acid pump antagonist, exerts anti-inflammatory action against
      Helicobacter pylori-induced COX-2 expression by inactivating Akt signaling.
AB  - Chronic gastric inflammation developing after Helicobacter pylori (H. pylori)
      infection is responsible for either dyspeptic symptom relevant to
      gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants,
      especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as
      well as the eradication regimen. Among several mediators engaged in propagating
      gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be
      the principal one, and several prescriptions have been made for decreasing the
      COX-2 levels. Multiple line of evidence are available for anti-inflammatory
      action of PPIs beyond acid suppression, but revaprazan, a novel acid pump
      antagonist launched in clinic, has also been suggested to exert significant anti
      inflammatory actions as much as PPI. In the current study, we hypothesized that
      revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti
      inflammatory pharmacological actions. The changes of gastric COX-2 expression as
      well as responsible transcription factors were measured after H. pylori infection
      in the presence or absence of revaprazan. Infection of AGS cells with H. pylori
      induced significant up-regulation of COX-2 in time- and concentration-dependent
      manners, which was mediated by Akt phosphorylation. Revaprazan treatment
      significantly inhibited IkappaB-alpha degradation as well as Akt inactivation,
      resulting in attenuation of H. pylori-induced COX-2 expression. Additional
      rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted.
      In conclusion, revaprazan imposed significant anti-inflammatory actions on H.
      pylori infection beyond acid suppression.

PMID- 22962523
TI  - Bovine lactoferrin ameliorates ferric nitrilotriacetate-induced renal oxidative
      damage in rats.
AB  - Milk provides a well-balanced source of amino acids and other ingredients. One of
      the functional ingredients in milk is lactoferrin (LF). LF presents a wide
      variety of bioactivities and functions as a radical scavenger in models using
      iron-ascorbate complexes and asbestos. Human clinical trials of oral LF
      administration for the prevention of colon polyps have been successful and
      demonstrated that dietary compounds exhibit direct interactions. However,
      antioxidative properties of LF in distant organs require further investigation.
      To study the antioxidant property of LF, we employed bovine lactoferrin (bLF)
      using the rat model of ferric nitrilotriacetate (Fe-NTA)-induced renal tubular
      oxidative injury. We fed rats with bLF (0.05%, w/w) in basal chow for 4 weeks and
      sacrificed them after Fe-NTA treatment. After intraperitoneal administration of
      9.0 mg iron/kg Fe-NTA for 4 and 24 h, bLF pretreatment suppressed elevation of
      serum creatinine and blood urea nitrogen levels. In addition, we observed
      protective effects against renal oxidative tubular damage and maintenance of
      antioxidant enzyme activities in the bLF-pretreated group. We thus demonstrated
      the antioxidative effect of bLF against Fe-NTA-induced renal oxidative injury.
      These results suggest that LF intake is useful for the prevention of renal
      tubular oxidative damage mediated by iron.

PMID- 22962524
TI  - Effect of the smell of Seirogan, a wood creosote, on dermal and intestinal
      mucosal immunity and allergic inflammation.
AB  - Seirogan, a wood creosote, has been used as an antidiarrhetic drug in Asian
      countries including Japan for many years. This antidiarrhetic has recently been
      used as a sugar-coated pill because Seirogan has a strong smell. The strong smell
      of the uncoated form of Seirogan may modulate the defense systems of animals
      because the sense of smell is important for the detection of toxic metabolites in
      foods contaminated with pathogens. This study examined the effect of the sugar
      coated and uncoated forms of this antidiarrhetic on the immunological response
      and inflammatory reactions in mice that had been sensitized with either
      fluorescein isothiocyanate or oxazolone. The sensitization of mice with either
      FITC or oxazolone markedly increased the plasma levels of tumor necrosis factor
      alpha and mucosal IgA and elicited severe inflammation in the colon by a
      mechanism that could be suppressed by exposure of animals to the smell of
      uncoated Seirogan as effectively as the oral administration of the agent. Dermal
      inflammation in the FITC- and oxazolone-sensitized mice was also suppressed
      effectively either by the exposure to the smell or oral administration of the
      agent. Biochemical and histochemical analyses revealed that the elevated levels
      of plasma tumor necrosis factor-alpha and mucosal IgA were significantly
      decreased by exposure to the smell of uncoated Seirogan as well as by oral
      administration of the agent. Exposure of mice to the smell of Seirogan but not
      oral administration of the agent selectively increased plasma levels of
      adrenocorticotropic hormone and cortisol, particularly in the sensitized animals.
      These observations suggest that exposing the animals to the smell of Seirogan per
      se activated the hypothalamo-pituitary-adrenal axis and systemically modulated
      immunological reactions to suppress the allergic reactions.

PMID- 22962525
TI  - Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice.
AB  - The antidiabetic effects of lactic acid bacteria were investigated using mice. In
      Experiment 1, normal ICR mice were loaded with sucrose or starch with or without
      viable Lactobacillus rhamnosus GG cells. GG significantly inhibited postprandial
      blood glucose levels when administered with sucrose or starch. In Experiment 2,
      KK-A(y) mice, a model of genetic type 2 diabetes, were given a basal diet
      containing viable GG cells or viable Lactobacillus delbrueckii subsp. bulgaricus
      cells for 6 weeks. Viable GG cells significantly inhibited fasting blood glucose,
      postprandial blood glucose in a glucose tolerance test and HbA1c. Such effects
      were not shown by viable L. bulgaricus cells. In Experiment 3, the KK-A(y) mice
      were given a basal diet containing viable GG cells or heat-treated GG cells for 3
      weeks. The viable GG cells significantly suppressed fasting blood glucose and
      impaired glucose tolerance, but the heat-treated GG showed no effects. These
      results demonstrated that GG decreased the postprandial blood glucose in ICR
      mice, and that the antidiabetic activity of lactic acid bacteria on the KK-A(y)
      mice differed depending on the bacterial strain and whether the bacterium is
      viable when it arrives in the intestine. In the present study, we conclude that
      the antidiabetic activity may result from continuous inhibition of the
      postprandial blood glucose through suppression of glucose absorption from the
      intestine. These findings indicate that specific strains of lactic acid bacterium
      can be expected to be beneficial for the management of type 2 diabetes.

PMID- 22962526
TI  - Effects of astaxanthin-rich Haematococcus pluvialis extract on cognitive
      function: a randomised, double-blind, placebo-controlled study.
AB  - In this study we tried to confirm the effect of an astaxanthin-rich Haematococcus
      pluvialis extract on cognitive function in 96 subjects by a randomised double
      blind placebo-controlled study. Healthy middle-aged and elderly subjects who
      complained of age-related forgetfulness were recruited. Ninety-six subjects were
      selected from the initial screen, and ingested a capsule containing astaxanthin
      rich Haematococcus pluvialis extract, or a placebo capsule for 12 weeks.
      Somatometry, haematology, urine screens, and CogHealth and Groton Maze Learning
      Test were performed before and after every 4 weeks of administration. Changes in
      cognitive performance and the safety of astaxanthin-rich Haematococcus pluvialis
      extract administration were evaluated. CogHealth battery scores improved in the
      high-dosage group (12 mg astaxanthin/day) after 12 weeks. Groton Maze Learning
      Test scores improved earlier in the low-dosage (6 mg astaxanthin/day) and high
      dosage groups than in the placebo group. The sample size, however, was small to
      show a significant difference in cognitive function between the astaxanthin-rich
      Haematococcus pluvialis extract and placebo groups. No adverse effect on the
      subjects was observed throughout this study. In conclusion, the results suggested
      that astaxanthin-rich Haematococcus pluvialis extract improves cognitive function
      in the healthy aged individuals.

PMID- 22962527
TI  - Gingival vascular functions are altered in type 2 diabetes mellitus model and/or
      periodontitis model.
AB  - The association of vascular reactivity between diabetes and periodontal disease
      has not been clarified. Gingival blood flow was measured by laser Doppler
      flowmetry for 31 weeks in Wistar rats, Wistar rats orally challenged with
      Porphyromonas gingivalis (Wistar rats + Porphyromonas gingivalis), Goto-Kakizaki
      rats, and Goto-Kakizaki rats orally challenged with Porphyromonas gingivalis
      (Goto-Kakizaki rats + Porphyromonas gingivalis). Effects of alveolar bone
      resorption on periodontal tissue was enhanced in Wistar rats + Porphyromonas
      gingivalis, and Goto-Kakizaki rats, with this effect being significantly enhanced
      by Goto-Kakizaki rats + Porphyromonas gingivalis. Using the L-band electron spin
      resonance technique, we succeeded in measuring oxidative stress as decay rate
      constant (K(1) and K(2)) of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy in
      the oral and maxillofacial region of the animal models. The decay rate constant
      (K(1)) of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy was significantly
      greater in the oral and maxillofacial region of Goto-Kakizaki rats +
      Porphyromonas gingivalis compared to Wistar rats, Wistar rats + Porphyromonas
      gingivalis and Goto-Kakizaki rats groups. Gingival reactive hyperemia was
      attenuated by periodontal disease, and this effect was also remarkable in the
      diabetes mellitus model. Taken together, we found that vascular endothelial
      function was decreased in diabetes mellitus and/or periodontal disease animal
      models due to increasing oxidative stress in the gingival circulation.

PMID- 22962528
TI  - Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor
      amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy.
AB  - The aim of this study was to compare the efficacy and tolerability of the first
      line Helicobacter pylori (H. pylori) eradication regimen composed of proton pump
      inhibitor, clarithromycin, and amoxicillin, with those of a regimen composed of
      proton pump inhibitor, metronidazole, and amoxicillin. Data of patients, who were
      administered the first-line H. pylori eradication regimen at Tokyo Medical Center
      between 2008 and 2011, were reviewed. All patients had H. pylori gastritis
      without peptic ulcer disease. The 7-day triple regimen composed of lansoprazole,
      clarithromycin, and amoxicillin was administered to 55 patients, and that
      composed of omeprazole, metronidazole, and amoxicillin was administered to 55
      patients. Intention-to-treat and per-protocol eradication rates were 74.5 and
      80.4%, respectively, for the regimen of lansoprazole, clarithromycin, and
      amoxicillin, whereas the corresponding rates were 96.4 and 100%, respectively,
      for the regimen of omeprazole, metronidazole, and amoxicillin. In conclusion,
      first-line H. pylori eradication therapy composed of omeprazole, metronidazole,
      and amoxicillin was significantly more effective than that composed of
      lansoprazole, clarithromycin, and amoxicillin, without differences in
      tolerability.

PMID- 22962529
TI  - Multiple free-radical scavenging capacity in serum.
AB  - We have developed a method to determine serum scavenging-capacity profile against
      multiple free radical species, namely hydroxyl radical, superoxide radical,
      alkoxyl radical, alkylperoxyl radical, alkyl radical, and singlet oxygen. This
      method was applied to a cohort of chronic kidney disease patients. Each free
      radical species was produced with a common experimental procedure; i.e.,
      uv/visible-light photolysis of free-radical precursor/sensitizer. The decrease in
      free-radical concentration by the presence of serum was quantified with electron
      spin resonance spin trapping method, from which the scavenging capacity was
      calculated. There was a significant capacity change in the disease group (n = 45)
      as compared with the healthy control group (n = 30). The percent values of
      disease's scavenging capacity with respect to control group indicated
      statistically significant differences in all free-radical species except
      alkylperoxyl radical, i.e., hydroxyl radical, 73 +/- 12% (p = 0.001); superoxide
      radical, 158 +/- 50% (p = 0.001); alkoxyl radical, 121 +/- 30% (p = 0.005);
      alkylperoxyl radical, 123 +/- 32% (p>0.1); alkyl radical, 26 +/- 14% (p = 0.001);
      and singlet oxygen, 57 +/- 18% (p = 0.001). The scavenging capacity profile was
      illustrated using a radar chart, clearly demonstrating the characteristic change
      in the disease group. Although the cause of the scavenging capacity change by the
      disease state is not completely understood, the profile of multiple radical
      scavenging capacities may become a useful diagnostic tool.

PMID- 22962530
TI  - Cytoprotective effect of chlorogenic acid against alpha-synuclein-related
      toxicity in catecholaminergic PC12 cells.
AB  - Parkinson's disease is a major neurodegenerative disease involving the selective
      degeneration of dopaminergic neurons and alpha-synuclein containing Lewy bodies
      formation in the substantia nigra. Although alpha-synuclein is a key molecule for
      both dopaminergic neuron death and the formation of inclusion bodies, the
      mechanism of alpha-synuclein induction of Parkinson's disease-related
      pathogenesis is not understood. In the present study, we found that the
      interaction between dopamine and alpha-synuclein requires the oxidation of
      dopamine. Furthermore, we examined the protective effect of chlorogenic acid, a
      major polyphenol contained in coffee, against alpha-syn and dopamine-related
      toxicity. Chlorogenic acid inhibits several DA/alpha-synuclein-related
      phenomenon, including the oxidation of dopamine, the interaction of oxidized
      dopamine with alpha-synuclein, and the oligomerization of alpha-synuclein under
      dopamine existing conditions in vitro. Finally, we showed that the cytoprotective
      effect against alpha-synuclein-related toxicity in PC12 cells that can be
      controlled by the Tet-Off system. Although the induction of alpha-synuclein in
      catecholaminergic PC12 cells causes a decrease in cell viability, chlorogenic
      acid rescued this cytotoxicity significantly in a dose dependent manner. These
      results suggest that the interaction of oxidized DA with alpha-synuclein may be a
      novel therapeutic target for Parkinson's disease, and polyphenols, including
      chlorogenic acid, are candidates as protective and preventive agents for
      Parkinson's disease onset.

PMID- 22962531
TI  - The effect of irradiation wavelengths and the crystal structures of titanium
      dioxide on the formation of singlet oxygen for bacterial killing.
AB  - Safe and effective methods for oral bacterial disinfection have been desired,
      since bacteria cause many infectious diseases such as dental caries, periodontal
      disease, and endodontic infections. Singlet oxygen ((1)O(2)) is attractive,
      because it is toxic to prokaryotic cells, but not to eukaryotic cells. We
      selected irradiation of titanium dioxide (TiO(2)) as a source of (1)O(2), because
      it has been used in sunscreens and cosmetic products without complications. In
      order to establish the optimal oral photodynamic therapy conditions, we measured
      the rate of (1)O(2) formation from the irradiated anatase or rutile forms of
      TiO(2) using 365 or 405 nm lamps. The rate of (1)O(2) formation decreased in the
      following order: anatase, 365 nm > rutile, 405 nm > rutile, 365 nm > anatase, 405
      nm. Therefore, we concluded that irradiation of the rutile form of TiO(2) by a
      405 nm lamp is the most favorable photodynamic therapy condition, because visible
      light is more desirable than UV light from the viewpoint of patient safety. We
      also confirmed that there was no direct HO(*) formation from the irradiated
      TiO(2).

PMID- 22962532
TI  - Hyperhomocysteinemia is a risk factor for colorectal adenoma in women.
AB  - Homocysteine is involved in a one-carbon transfer reaction, which is important
      for DNA synthesis and methylation. High level of plasma homocysteine, biochemical
      marker of folate status, is known to be a risk factor for cancer. However, it is
      inconclusive as to whether plasma homocysteine concentration can predict
      colorectal adenoma. We conducted a case-control study to determine whether
      hyperhomocysteinemia is a risk factor for adenoma. Data from 1,039 subjects who
      underwent a colonoscopy and plasma homocysteine concentration determination
      during health examinations at single center over a two-year period were analyzed.
      The subjects were classified into two groups (422 adenoma and 617 controls).
      Subjects defined as having advanced adenomas were those with more than three
      adenomas, over 1 cm in size, high grade dysplasia, or villous components. Male,
      old age, high body mass index, low high-density lipoprotein-cholesterol, smoking,
      fasting glucose, and past history of colon polyps were significantly associated
      with adenoma according to multiple logistic regression. According to subgroup
      analysis by gender, plasma homocysteine concentration was not associated with
      adenoma in males; however, a high plasma homocysteine concentration significantly
      increased the risk of adenoma as well as advanced adenoma in females.
      Hyperhomocysteinemia is a risk factor for colorectal adenoma in women.

PMID- 22962533
TI  - Disruption of non-enzymatic antioxidant defense systems in the brain of rats with
      water-immersion restraint stress.
AB  - We examined whether non-enzymatic antioxidant defense systems are disrupted in
      the brain of rats with water-immersion restraint stress. When rats were exposed
      to water-immersion restraint stress for 1.5, 3 or 6 h, the brain had decreased
      ascorbic acid and reduced glutathione contents and increased lipid peroxide and
      nitric oxide metabolites contents at 3 h and showed further changes in these
      components with a reduction of vitamin E content at 6 h. Increased serum levels
      of stress markers were found at 1.5, 3 or 6 h of WIRS. Oral pre-administration of
      L-ascorbic acid (1.5 mmol/kg) or vitamin E (0.5 mmol/kg) to rats with 6 h of
      water-immersion restraint stress attenuated the increases in lipid peroxide and
      nitric oxide metabolites contents and the decrease in vitamin E content in the
      brain. Pre-administered L-ascorbic acid attenuated the decreases in brain
      ascorbic acid and reduced glutathione contents at 6 h of water-immersion
      restraint stress, while pre-administered vitamin E enhanced the decreases in
      those contents. Pre-administered L-ascorbic acid or vitamin E did not affect the
      increased serum levels of stress markers in rats with 6 h of water-immersion
      restraint stress. These results indicate that water-immersion restraint stress
      causes disruption of non-enzymatic antioxidant defense systems through enhanced
      lipid peroxidation and nitric oxide generation in the brain of rats with water
      immersion restraint stress.

PMID- 22962534
TI  - Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric
      dimethylarginine pathway in rat type II diabetic nephropathy.
AB  - An impaired generation of nitric oxide has been associated with diabetic renal
      disease. In order to elucidate the underlying molecular mechanisms into how
      nitric oxide synthesis is impaired in diabetic renal disease, we examined changes
      in activities and expressions of some renal enzymes involved in nitric oxide
      production during the development of diabetic nephropathy in type II diabetic
      Otsuka Long-Evans Tokushima Fatty rats. Ten-week old Otsuka Long-Evans Tokushima
      Fatty (n = 40) and control Long-Evans Tokushima Otsuka rats (n = 20) were given
      drinking water containing 20% sucrose to accelerate the development of diabetic
      nephropathy. Otsuka Long-Evans Tokushima Fatty rats developed diabetic
      nephropathy in an age-dependent manner. Renal nitric oxide synthase activities in
      Otsuka Long-Evans Tokushima Fatty rats gradually declined with the progression of
      diabetic mellitus and were significantly lower than those of age-matched Long
      Evans Tokushima Otsuka rats after 22 weeks of age. The lower activities of renal
      nitric oxide synthase in Otsuka Long-Evans Tokushima Fatty rats were correlated
      with relatively higher levels of renal free asymmetric dimethylarginine, an
      endogenous nitric oxide synthase inhibitor, and were also correlated with
      decreased activities of dimethylargininedimethylaminohydrolase which metabolizes
      asymmetric dimethylarginine to citrulline. These results imply that
      dimethylargininedimethylaminohydrolase dysregulation may play an important role
      in the development of diabetic nephropathy by increasing asymmetric
      dimethylarginine levels, which leads to inhibition of renal nitric oxide
      synthesis.

PMID- 22962535
TI  - Plasma phospholipid fatty acid composition and estimated desaturase activity in
      heart failure patients with metabolic syndrome.
AB  - Metabolic syndrome is one of the major factors to increase the incidence of heart
      failure. In our study, we compared plasma fatty acid compositions among heart
      failure patients with and without Metabolic syndrome. Fatty acid (FA) composition
      of plasma phospholipids was analyzed and the activities of desaturase were
      estimated as the ratio of substrate and product fatty acids in 85 stable heart
      failure patients. Fatty acid and estimated desaturase activities were further
      examined for their associations with Metabolic syndrome components. Heart failure
      patients with Metabolic syndrome showed significant changes in fatty acid
      composition in comparison to those without Metabolic syndrome, which had a
      decreased proportion of lauric acid (C12:0) and an increased proportion of dihomo
      gamma-linolenic acid (C20:3n-6). Also, estimated desaturase activities (D5D and
      D6D) were closely related to Metabolic syndrome condition among heart failure
      patients. The content of dihomo-gamma-linolenic acid showed positive correlations
      with BMI, waist circumference, and plasma triglyceride levels. D6D were
      positively associated with plasma triglyceride levels, whereas D5D showed a
      negative correlation with plasma triglyceride levels and waist circumferences.
      The content of dihomo-gamma-linolenic acid as well as estimated D6D and D5D were
      altered in heart failure patients with Metabolic syndrome.

PMID- 22962537
TI  - Editorial letter.

PMID- 22962538
TI  - INDIRECT INTELLIGENT SLIDING MODE CONTROL OF A SHAPE MEMORY ALLOY ACTUATED
      FLEXIBLE BEAM USING HYSTERETIC RECURRENT NEURAL NETWORKS.
AB  - This paper introduces an indirect intelligent sliding mode controller (IISMC) for
      shape memory alloy (SMA) actuators, specifically a flexible beam deflected by a
      single offset SMA tendon. The controller manipulates applied voltage, which
      alters SMA tendon temperature to track reference bending angles. A hysteretic
      recurrent neural network (HRNN) captures the nonlinear, hysteretic relationship
      between SMA temperature and bending angle. The variable structure control
      strategy provides robustness to model uncertainties and parameter variations,
      while effectively compensating for system nonlinearities, achieving superior
      tracking compared to an optimized PI controller.

PMID- 22962536
TI  - Synergistic effect of isoflavone glycosides and fructooligosaccharides on
      postgastrectomy osteopenia in rats.
AB  - Fructooligosaccharides stimulate the growth of Bifidobacteria, which cleave
      isoflavone glycosides to yield corresponding aglycones, and convert metabolites
      by enhancing enterohepatic recirculation of isoflavones in rats. In the present
      study, we determined the synergistic effect of dietary isoflavone glycosides and
      fructooligosaccharides on postgastrectomy osteopenia in rats. Nine-week-old male
      Sprague-Dawley rats were gastrectomized (n = 20) or sham operated, (control, n =
      5) and then randomly assigned to 5 diet groups: sham-a purified diet control,
      gastrectomized-control, gastrectomized-isoflavone (0.2% isoflavone glycosides),
      gastrectomized-fructooligosaccharides (7.5% fructooligosaccharides), and
      isoflavone and fructooligosaccharides (0.2% isoflavone glycosides + 7.5%
      fructooligosaccharides). After 6 weeks, the rats were killed and biological
      samples were collected. In gastrectomized rats, fructooligosaccharides prevented
      femoral bone fragility, but isoflavone without fructooligosaccharides did not
      inhibit postgastrectomy osteopenia. Isoflavone and fructooligosaccharides
      exhibited a synergistic in the distal metaphyseal trabecular bone, indicated by
      peripheral quantitative computed tomography. Moreover, fructooligosaccharides
      increased calcium absorption and equol production from daidzein in gastrectomized
      rats. These results indicate that isoflavone alone did not inhibit
      postgastrectomy osteopenia, but the combination of isoflavone and
      fructooligosaccharides improved the inhibition of trabecular bone loss by
      increasing calcium absorption and equol production through fructooligosaccharides
      supplementation.

PMID- 22962539
TI  - SPECIES COMPOSITION, DISTRIBUTION, LIFE FORMS AND FOLK NOMENCLATURE OF FOREST AND
      COMMON LAND PLANTS OF WESTERN CHITWAN, NEPAL.
AB  - This paper enumerates 349 plant species belonging to 77 families of vascular
      plants collected in the winter seasons of 1996 and 2000 by the flora teams of the
      Population and Ecology Research Laboratory, Nepal. Of the total species, 249
      species belong to dicotyledons, 87 species to monocotyledons and 13 species to
      pteridophytes. Among the families, dicotyledons contributed the highest number of
      families (55 in number) followed by monocotyledons and pteridophytes. In the
      study areas, species composition varies with the type of habitats in the study
      plots. Some species are unique in distribution. The highest unique species are
      contributed by common lands (87 spp.), followed by the Chitwan National Park
      forest (36 spp.) and Tikauli forest (32 spp.). Ageratum houstonianum Mill.,
      Cynodon dactylon (L.) Pers., Imperata cylindrica (L.) Beauv., Rungia parviflora
      (Retz.) Nees, Saccharum spontaneum L. and Thelypteris auriculata (J. Sm.) K.
      Iwats are the most common species across all the research blocks. Of the listed
      plants, many plants have local names either in Nepalese or other tribal
      languages. Plants are named in different ways on the basis of habit, habitat,
      smell, taste, and morphological characters of the plants, which are also the
      basis of nomenclature in plant taxonomy.

PMID- 22962540
TI  - DNA Supercoiling and Repair in Peripheral Lymphocytes as a Measure of Acute
      Radiation Response After Radiotherapy.
AB  - DNA supercoiling density and incision kinetics during ultraviolet (UV) excision
      repair hav been measured in lymphocytes from 20 cancer patients and 17 healthy
      donors. Nucleoid sedimentation was used, which allows the sensitive detection of
      both DNA damage and alterations in chromatin structure. The release of DNA
      supercoiling after ethidium bromide intercalation and the kinetics of the
      incision step following UV irradiation were compared in lymphocytes derived from
      cancer patients and those from normal donors. The classification into lymphocytes
      with normal or reduced repair and normal or altered supercoiling, respectively,
      revealed that reduced repair as well as altered chromatin structure occurred more
      frequently in lymphocytes derived from patients (40% and 85%, respectively) than
      in those from healthy donors (35% and 23%, respectively). Even more striking was
      the simultaneous occurrence of both characteristics in tumor patients: in 34% of
      all cases reduced repair was associated with altered supercoiling density,
      whereas among healthy donors this association occurred in only 18% of all cases.
      Supercoiling density may be related to functional integrity of lymphocytes and
      repair capacity to recovery after radiation damage. Since both parameters are
      important for the radiation response of normal tissue, we consider these
      measurements a potential prognostic assay aimed at reducing acute reaction of the
      normal tissue.

PMID- 22962541
TI  - "It Was Basically College to Us": Poverty, Prison, and Emerging Adulthood.
AB  - With the tremendous rise in the United States' incarceration rates over the last
      four decades, historically high numbers of young African Americans are spending
      their "emerging adulthood" (as theorized by Arnett) in close contact with the
      penitentiary. In contrast to the exploration of future possibilities facilitated
      by academic, military, and professional institutions geared toward people in this
      life stage, imprisonment typically restricts one's social, occupational, and
      civic opportunities during and after confinement. In this article, I draw on in
      depth interviews with young men who had recently exited state prison and their
      intimate partners to probe the meanings of incarceration for emerging adults in
      the neoliberal era. This investigation invokes Merton and Barber's concept of
      sociological ambivalence, Blankenship's discussion of sociological thriving, and
      Bourdieu's notion of amor fati to analyze the paradoxically positive accounts
      offered by young people when describing their early experiences with the prison.
      I argue that these narratives must be interpreted in the broader context of
      diminished social welfare and intensified socioeconomic disadvantage that force
      poor people to turn to a punitive institution as a "resource" for the social
      goods distributed through valorized channels to their more privileged peers. This
      analysis invites further research by highlighting the necessity of developing a
      thorough understanding of the dominant role of the prison as a shaping
      institution at a critical juncture in the lives of those born into poverty.

PMID- 22962542
TI  - Rediscovering Hydrogel-Based Double-Diffusion Systems for Studying
      Biomineralization.
AB  - For those seeking to model biomineralization in vitro, hydrogels can serve as
      excellent models of the extracellular matrix (ECM) microenvironment. A major
      challenge posed in implementing such systems is the logistics involved, from
      fundamental engineering to experimental design. For the study of calcium
      phosphate (e.g., hydroxyapatite) formation, many researchers use hydrogel-based
      double-diffusion systems (DDSs). The various designs of these DDSs are seemingly
      as unique as their applications. In this Highlight, we present a survey of four
      distinct types of double-diffusion systems and evaluate them in the context of
      fundamental diffusion theory. Based upon this analysis, we present the design and
      evaluation of an optimized system. The techniques and framework for the
      evaluation and construction of a DDS presented here can be applied to any DDS
      that a researcher may want to implement for their particular studies of
      biomineralization.

PMID- 22962543
TI  - Anxiety among Black and Latina Mothers of Premature Infants at Social
      Environmental Risk.
AB  - Anxiety is heightened for mothers of premature infants, potentially interfering
      with early mothering. This study describes relationships among race/ethnicity,
      language, and anxiety for women at social-environmental risk who deliver a
      premature infant. Postnatal baseline interview data from a randomized trial
      testing a behavioral intervention for mothers and infants (29-34 weeks
      gestational age) were used to examine maternal state (STAI-Y1) and trait (STAI
      Y2) anxiety among blacks and Latinas, and by language preference. Latinas (n =
      97) had an elevated prevalence of high (>= 40) state anxiety compared to blacks
      (n = 97), with Latinas preferring a Spanish to an English interview reporting the
      highest levels of state anxiety. Trait anxiety did not differ across groups.
      Culturally appropriate interventions are needed to reduce anxiety among Latina
      mothers delivering premature infants, especially among those with limited English
      language proficiency. A racially/ethnically diverse workforce, bilingual
      healthcare providers, and trained medical interpreters may help to ensure better
      outcomes.

PMID- 22962544
TI  - Cultural Approaches to Parenting.
AB  - This article first introduces some main ideas behind culture and parenting and
      next addresses philosophical rationales and methodological considerations central
      to cultural approaches to parenting, including a brief account of a cross
      cultural study of parenting. It then focuses on universals, specifics, and
      distinctions between form (behavior) and function (meaning) in parenting as
      embedded in culture. The article concludes by pointing to social policy
      implications as well as future directions prompted by a cultural approach to
      parenting.

PMID- 22962545
TI  - The Global Distribution of Infant Mortality: A subnational spatial view.
AB  - We describe the compilation of a spatially explicit dataset detailing infant
      mortality rates in over 10,000 national and subnational units worldwide,
      benchmarked to the year 2000. Although their resolution is highly variable,
      subnational data are available for countries representing over 90% of non-OECD
      population. Concentration of global infant deaths is higher than implied by
      national data alone. Assigning both national and subnational data to map grid
      cells so that they may be easily integrated with other geographic data, we
      generate infant mortality rates for environmental regions, including biomes and
      coastal zones, by continent. Rates for these regions also show striking
      refinements from the use of the higher resolution data. Possibilities and
      limitations for related work are discussed.

PMID- 22962546
TI  - A Preliminary Feasibility Study of Varenicline for Smoking Cessation in Bipolar
      Disorder.

PMID- 22962548
TI  - The effect of precipitants on Ni-Al(2)O(3) catalysts prepared by a co
      precipitation method for internal reforming in molten carbonate fuel cells.
AB  - Ni-Al(2)O(3) catalysts are prepared via the co-precipitation method using various
      precipitants: urea, Na(2)CO(3), NaOH, K(2)CO(3), KOH and NH(4)OH. The effects of
      the precipitants on the physicochemical properties and catalytic activities of
      the Ni-Al(2)O(3) catalysts are investigated. The Ni50-urea catalyst displays the
      largest specific surface area and the highest pore volume. This catalyst also
      exhibits the highest Ni dispersion and the largest Ni surface area. Ni50-urea
      catalyst prepared with urea as precipitant and Ni50-K(2)CO(3) catalyst prepared
      with K(2)CO(3) as precipitant exhibit high pore volumes and good catalytic
      activities for methane steam reforming. The Ni50-urea catalyst exhibits the best
      physicochemical properties and shows good catalytic activity and a strong
      resistance to electrolyte contamination.

PMID- 22962547
TI  - Substance Abuse Recovery after Experiencing Homelessness and Mental Illness: Case
      Studies of Change Over Time.
AB  - OBJECTIVE: This paper addresses how consumers with dual diagnosis, who were
      formerly homeless but are now living in supportive housing, understand their
      recovery from substance abuse (i.e., substance abuse or dependence).
      Specifically, this study examined: What can be learned about substance abuse
      recovery from consumers considered to be doing well; how past substance abuse
      fits into their present-day narratives; and how (if at all) policies of harm
      reduction versus abstinence are regarded as affecting recovery efforts.  METHODS:
      As part of a federally-funded qualitative study, 38 individuals who met criteria
      for having achieved a measure of success in mental health recovery were
      purposively sampled from two supportive housing agencies - one using a harm
      reduction and the other an abstinence model. Researchers conducted in-depth
      interviews and used case study analysis, the latter including the development of
      case summaries and data matrices, to focus on substance abuse recovery in the
      larger context of participants' lives.  RESULTS: Recovery from substance abuse
      was depicted as occurring either through discrete decisions or gradual processes;
      achieving recovery was distinct from maintaining recovery. Emergent themes
      related to achievement included: (a) pivotal events and people (b) maturation,
      and (c) institutionalization. Central themes to maintaining recovery were: (a)
      housing, (b) self-help, and (c) the influence of significant others. 
      CONCLUSIONS: These findings capture a complex picture of overcoming substance
      abuse that largely took place outside of formal treatment and was heavily
      dependent on broader contexts. Equally important is that consumers themselves did
      not necessarily view substance abuse recovery as a defining feature of their life
      story. Indeed, recovery from substance abuse was seen as overcoming one adversity
      among many others during their troubled life courses.

PMID- 22962549
TI  - Evolutionary mechanics: new engineering principles for the emergence of
      flexibility in a dynamic and uncertain world.
AB  - Engineered systems are designed to deftly operate under predetermined conditions
      yet are notoriously fragile when unexpected perturbations arise. In contrast,
      biological systems operate in a highly flexible manner; learn quickly adequate
      responses to novel conditions, and evolve new routines and traits to remain
      competitive under persistent environmental change. A recent theory on the origins
      of biological flexibility has proposed that degeneracy-the existence of multi
      functional components with partially overlapping functions-is a primary
      determinant of the robustness and adaptability found in evolved systems. While
      degeneracy's contribution to biological flexibility is well documented, there has
      been little investigation of degeneracy design principles for achieving
      flexibility in systems engineering. Actually, the conditions that can lead to
      degeneracy are routinely eliminated in engineering design. With the planning of
      transportation vehicle fleets taken as a case study, this article reports
      evidence that degeneracy improves the robustness and adaptability of a simulated
      fleet towards unpredicted changes in task requirements without incurring costs to
      fleet efficiency. We find that degeneracy supports faster rates of design
      adaptation and ultimately leads to better fleet designs. In investigating the
      limitations of degeneracy as a design principle, we consider decision-making
      difficulties that arise from degeneracy's influence on fleet complexity. While
      global decision-making becomes more challenging, we also find degeneracy
      accommodates rapid distributed decision-making leading to (near-optimal) robust
      system performance. Given the range of conditions where favorable short-term and
      long-term performance outcomes are observed, we propose that degeneracy may
      fundamentally alter the propensity for adaptation and is useful within different
      engineering and planning contexts.

PMID- 22962550
TI  - Performance of pre-commercial release formulations of spinosad against five
      stored-product insect species on four stored commodities.
AB  - Two liquid and one dry pre-commercial release spinosad formulations were
      evaluated at the labeled rate of 1 ppm against five stored-grain insect species
      on wheat, short-grain rice, long-grain rice, and maize. Except on maize, efficacy
      of spinosad was compared with a currently registered grain protectant,
      chlorpyrifos-methyl (3 ppm) plus deltamethrin (0.5 ppm). The 7- and 14-day
      mortalities of the lesser grain borer, Rhyzopertha dominica, were 99.0-100.0% on
      spinosad and chlorpyrifos-methyl plus deltamethrin-treated wheat, short-grain
      rice, and long-grain rice. Adult progeny of R. dominica after 42 days on these
      commodities decreased by 99.7-100.0% relative to progeny production on untreated
      wheat. Mortality and reduction in adult progeny of the rice weevil, Sitophilus
      oryzae, on the three commodities, and that of the maize weevil, Sitophilus
      zeamais, on maize and the red flour beetle, Tribolium castaneum, on wheat were
      100.0% only with chlorpyrifos-methyl plus deltamethrin. The liquid spinosad
      formulations were most effective against the Indianmeal moth, Plodia
      interpunctella, on maize and wheat. Except for R. dominica, the effectiveness of
      spinosad on the other species varied with the formulation, exposure time, and
      commodity. Chlorpyrifos-methyl plus deltamethrin was effective against insect
      species on the commodities tested.

PMID- 22962551
TI  - Cognitive factors affecting free recall, cued recall, and recognition tasks in
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: Our aim was to identify cognitive factors affecting free recall,
      cued recall, and recognition tasks in patients with Alzheimer's disease (AD).
      SUBJECTS: We recruited 349 consecutive AD patients who attended a memory clinic.
      METHODS: Each patient was assessed using the Alzheimer's Disease Assessment Scale
      (ADAS) and the extended 3-word recall test. In this task, each patient was asked
      to freely recall 3 previously presented words. If patients could not recall 1 or
      more of the target words, the examiner cued their recall by providing the
      category of the target word and then provided a forced-choice recognition of the
      target word with 2 distracters. The patients were divided into groups according
      to the results of the free recall, cued recall, and recognition tasks.
      Multivariate logistic regression analysis for repeated measures was carried out
      to evaluate the net effects of cognitive factors on the free recall, cued recall,
      and recognition tasks after controlling for the effects of age and recent memory
      deficit. RESULTS: Performance on the ADAS Orientation task was found to be
      related to performance on the free and cued recall tasks, performance on the ADAS
      Following Commands task was found to be related to performance on the cued recall
      task, and performance on the ADAS Ideational Praxis task was found to be related
      to performance on the free recall, cued recall, and recognition tasks.
      CONCLUSION: The extended 3-word recall test reflects deficits in a wider range of
      memory and other cognitive processes, including memory retention after
      interference, divided attention, and executive functions, compared with word-list
      recall tasks. The characteristics of the extended 3-word recall test may be
      advantageous for evaluating patients' memory impairments in daily living.

PMID- 22962552
TI  - Video Rating in Neurodegenerative Disease Clinical Trials: The Experience of
      PRION-1.
AB  - BACKGROUND/AIMS: Large clinical trials including patients with uncommon diseases
      involve assessors in different geographical locations, resulting in considerable
      inter-rater variability in assessment scores. As video recordings of
      examinations, which can be individually rated, may eliminate such variability, we
      measured the agreement between a single video rater and multiple examining
      physicians in the context of PRION-1, a clinical trial of the antimalarial drug
      quinacrine in human prion diseases. METHODS: We analysed a 43-component
      neurocognitive assessment battery, on 101 patients with Creutzfeldt-Jakob
      disease, focusing on the correlation and agreement between examining physicians
      and a single video rater. RESULTS: In total, 335 videos of examinations of 101
      patients who were video-recorded over the 4-year trial period were assessed. For
      neurocognitive examination, inter-observer concordance was generally excellent.
      Highly visual neurological examination domains (e.g. finger-nose-finger
      assessment of ataxia) had good inter-rater correlation, whereas those dependent
      on non-visual clues (e.g. power or reflexes) correlated poorly. Some non-visual
      neurological domains were surprisingly concordant, such as limb muscle tone.
      CONCLUSION: Cognitive assessments and selected neurological domains can be
      practically and accurately recorded in a clinical trial using video rating. Video
      recording of examinations is a valuable addition to any trial provided
      appropriate selection of assessment instruments is used and rigorous training of
      assessors is undertaken.

PMID- 22962553
TI  - Changes in phospholipid composition of erythrocyte membrane in Alzheimer's
      disease.
AB  - BACKGROUND: There are several reports indicating a decrease of ethanolamine
      plasmalogen (pl-PE) in brain tissues and in serum of patients with Alzheimer's
      disease (AD). The present study aimed to examine the composition of erythrocyte
      phospholipids including pl-PE in patients with AD. METHOD: A high-performance
      liquid chromatography (HPLC) method that can separate intact plasmalogens and all
      other phospholipid classes by a single chromatographic run was used. RESULTS: The
      ratios of pl-PE, phosphatidylethanolamine (PE) and phosphatidylserine (PS) to
      sphingomyelin were low as compared to those of the age-matched controls.
      CONCLUSION: These changes in erythrocyte phospholipids may reflect changes
      induced by oxidative stress, indicating the presence of high oxidative stress in
      the peripheral blood of AD patients.

PMID- 22962554
TI  - Role of APOE and Age at Enrollment in the Alzheimer's Disease Anti-Inflammatory
      Prevention Trial (ADAPT).
AB  - BACKGROUND: The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT)
      tested whether non-steroidal anti-inflammatory drugs (NSAIDs) can prevent
      Alzheimer's disease (AD). The results were null. We analyzed ADAPT data to
      examine if the effects of NSAIDs on AD risk differed depending upon APOE genotype
      or age as has been suggested by previous observational studies. METHODS: ADAPT
      randomized 2,528 cognitively intact older adults to either celecoxib, naproxen
      sodium or placebo; 2,388 participants provided blood samples for APOE genotyping.
      Proportional hazards regression was used to estimate the effects of naproxen or
      celecoxib versus placebo on incident AD by age at enrollment and APOE genotype.
      RESULTS: The proportion of subjects providing a biological sample did not differ
      between the treatment groups. In models of AD risk, none of the tests for 2-way
      interactions between either NSAID and age or APOE genotype were significant (p >
      0.05). CONCLUSIONS: The data did not support the hypothesis that the association
      between NSAIDs and AD risk differed by age or APOE genotype.

PMID- 22962555
TI  - An Open-Label Exploratory Study with Memantine: Correlation between Proton
      Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate
      Alzheimer's Disease.
AB  - AIM: To characterize progression of Alzheimer's disease (AD) using proton
      magnetic resonance spectroscopy ((1)H MRS). METHODS: Eleven subjects with mild to
      moderate AD underwent neurocognitive testing and single-voxel (1)H MRS from the
      precuneus and posterior cingulate region at baseline, after 24 weeks of
      monotherapy with a cholinesterase inhibitor, and after another 24 weeks of
      combination therapy with open-label memantine and a cholinesterase inhibitor.
      Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho),
      and creatine (Cr)] and their ratios in AD subjects were compared with those of an
      age-matched control group of 28 cognitively normal subjects. RESULTS: AD subjects
      had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI.
      Baseline Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS
      ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an
      increase in mI and a decrease in NAA/mI, but no significant change in other
      metabolites or ratios, or neurocognitive measures, when memantine was added to a
      cholinesterase inhibitor. CONCLUSION: Metabolite ratios significantly differed
      between AD and control subjects. Baseline metabolite ratios correlated with
      function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no
      changes in other metabolites, ratios, or cognitive measures, when memantine was
      added to a cholinesterase inhibitor.

PMID- 22962556
TI  - Speech therapy in primary progressive aphasia: a pilot study.
AB  - BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder
      with no effective pharmacological treatment. Cognition-based interventions are
      adequate alternatives, but their benefit has not been thoroughly explored. Our
      aim was to study the effect of speech and language therapy (SLT) on naming
      ability in PPA. METHODS: An open parallel prospective longitudinal study
      involving two centers was designed to compare patients with PPA submitted to SLT
      (1 h/week for 11 months) with patients receiving no therapy. Twenty patients were
      enrolled and undertook baseline language and neuropsychological assessments;
      among them, 10 received SLT and 10 constituted an age- and education-matched
      historical control group. The primary outcome measure was the change in group
      mean performance on the Snodgrass and Vanderwart naming test between baseline and
      follow-up assessments. RESULTS: Intervention and control groups did not
      significantly differ on demographic and clinical variables at baseline. A mixed
      repeated measures ANOVA revealed a significant main effect of therapy (F(1,18) =
      10.763; p = 0.005) on the performance on the Snodgrass and Vanderwart naming
      test. CONCLUSION: Although limited by a non-randomized open study design with a
      historical control group, the present study suggests that SLT may have a benefit
      in PPA, and it should prompt a randomized, controlled, rater-blind clinical
      trial.

PMID- 22962557
TI  - Clinical Approach to Diagnosis of Pre-Dementia Alzheimer's Disease (CAD-PAD).
AB  - OBJECTIVE: Our aim was to evaluate clinical and neuropsychological features to
      identify pre-dementia Alzheimer's disease (PAD) among mild cognitive impairment
      (MCI) patients. METHODS: A longitudinal prospective study of 89 consecutive
      patients affected with MCI was conducted. Clinical evaluation consisted of a
      clinical interview protocol, neuropsychological evaluation, standard laboratory
      tests, and CT scan. A 6-month clinical check-up was made to determine whether
      patients remained in MCI, improved or progressed to AD or another dementia.
      RESULTS: At 3-year follow-up, 47% patients developed AD dementia. Seventeen
      variables were significant and were evaluated by logistic regression analysis to
      identify the remaining optimal diagnostic criteria: age, gender, repeating
      comments, difficulties in understanding explanations, time of symptom evolution,
      history of depression, and word fluency (with animals) were identified with a
      sensitivity of 100% and a specificity of 93%. A computer application was
      developed with all these variables which we have named Clinical Approach to
      Diagnosis of PAD (CAD-PAD). CONCLUSIONS: These results suggest that CAD-PAD can
      help in the clinical diagnosis of PAD.

PMID- 22962558
TI  - Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild
      Cognitive Impairment.
AB  - BACKGROUND/AIMS: The role of cognitive reserve in Parkinson's disease (PD)-mild
      cognitive impairment (MCI) is incompletely understood. METHODS: The relationships
      between PD-MCI, years of education, and estimated premorbid IQ were examined in
      119 consecutive non-demented PD patients using logistic regression models.
      RESULTS: Higher education and IQ were associated with reduced odds of PD-MCI in
      univariate analysis. In multivariable analysis, a higher IQ was associated with a
      significantly decreased odds of PD-MCI, but education was not. CONCLUSION: The
      association of higher IQ and decreased odds of PD-MCI supports a role for
      cognitive reserve in PD, but further studies are needed to clarify the
      interaction of IQ and education and the impact of other contributors such as
      employment and hobbies.

PMID- 22962560
TI  - Community engagement in biobanking: Experiences from the eMERGE Network.
AB  - Advances in genomic technologies and the promise of "personalised medicine" have
      spurred the interest of researchers, healthcare systems, and the general public.
      However, the success of population-based genetic studies depends on the
      willingness of large numbers of individuals and diverse communities to grant
      researchers access to detailed medical and genetic information. Certain features
      of this kind of research - such as the establishment of biobanks and prospective
      data collection from participants' electronic medical records - make the
      potential risks and benefits to participants difficult to specify in advance.
      Therefore, community input into biobank processes is essential. In this report,
      we describe community engagement efforts undertaken by six United States
      biobanks, various outcomes from these engagements, and lessons learned. Our aim
      is to provide useful insights and potential strategies for the various
      disciplines that work with communities involved in biobank-based genomic
      research.

PMID- 22962559
TI  - Schizophrenia: from epidemiology to rehabilitation.
AB  - PURPOSE/OBJECTIVE: We discuss recent evidences about schizophrenia (frequency,
      onset, course, risk factors and genetics) and their influences to some
      epidemiological myths about schizophrenia diffuse between psychiatric and
      psychopathology clinicians. The scope is to evaluate if the new acquisitions may
      change the rehabilitation approaches to schizophrenia modifying the balance about
      the neurodevelopmental hypothesis of schizophrenia accepting that the cognitive
      deficits are produced by errors during the normal development of the brain
      (neurodevelopmental hypothesis) that remains stable in the course of illness and
      the neurodegenerative hypothesis according of which they derived from a
      degenerative process that goes on inexorably. RESEARCH METHOD/DESIGN: A review of
      the literature about epidemiology of schizophrenia has been performed and the
      contributions of some of these evidence to neurodevelopmental hypothesis and to
      rehabilitation has been described. RESULTS: It cannot be definitively concluded
      for or against the neurodevelopmental or degenerative hypothesis, but efforts in
      understanding basis of schizophrenia must go on. Until now, rehabilitation
      programs are based on the vulnerability-stress model: supposing an early deficit
      that go on stable during the life under favorable circumstances. So,
      rehabilitation approaches (as neuro-cognitive approaches, social skill training,
      cognitive-emotional training) are focused on the individual and micro-group
      coping skills, aiming to help people with schizophrenia to cope with
      environmental stress factors. CONCLUSIONS/IMPLICATIONS: Coping of cognitive
      deficits in schizophrenia may represents the starting-point for further research
      on schizophrenia, cohort studies and randomized trials are necessary to defined
      the range of effectiveness and the outcome of the treatments.

PMID- 22962561
TI  - The impact of concomitant medication use on patient eligibility for phase I
      cancer clinical trials.
AB  - Concomitant medication (CM) use may result in Phase I cancer clinical trial
      ineligibility due to concern for potential CM-investigational drug interactions
      or alteration of investigational drug absorption. Few studies have examined the
      impact of CM use on trial eligibility. METHODS: We reviewed records of 274
      patients on Phase I trials at a single academic institution. Demographics, CM
      identities and classes, CM discontinuation, reasons, and incidence of CM
      substitution were recorded. CM-investigational drug cytochrome P450 (CYP) enzyme
      interactions were documented. Statistical analysis was performed using
      descriptive statistics. RESULTS: 273 of 274 patients (99.6%, 95% confidence
      interval [CI] 98.9-100%) took CM, with a median of 8 CM per patient (range 0 -
      42). CM discontinuation occurred in 67 cases (25%, 95% CI 19-30%). The most
      common CM classes discontinued were herbal (17 cases, 25%, 95% CI 16-37%) and
      proton pump inhibitors (15 cases, 22%, 95% CI 12-32%). CM discontinuation reasons
      were: protocol prohibition (32 cases, 48%, 95% CI 36-60%); potential CM
      investigational drug interaction (25 cases, 37%, 95% CI 26-49%); other (10 cases,
      15%, 95% CI 6-23%). A potential CM-investigational drug CYP interaction was noted
      in 122 cases (45%, 95% CI 39-50%). CM potentially weakly decreased
      investigational drug metabolism in 52 cases (43%, 95% CI 34-51%), and potentially
      strongly decreased investigational drug metabolism in 17 cases (14%, 95% CI 8
      20%). Investigational drug potentially weakly decreased CM metabolism in 39 cases
      (32%, 95% CI 24-40%), and potentially strongly decreased CM metabolism in 28
      cases (23%, 95% CI 15-30%). CM substitution occurred in 36/67 cases (54%, 95% CI
      41-66%) where CM were discontinued to allow for eventual participation in
      clinical trials. Overall in 2 cases (0.7%, 95% CI 0.1-2.6%), patients were
      protocol ineligible because CM could not be discontinued or substituted.
      CONCLUSIONS: This study highlights the high prevalence of concomitant medication
      use among cancer patients enrolled in phase I clinical trials. Most patients did
      meet trial eligibility criteria with careful substitution and discontinuation of
      CM. The most common reason for discontinuation of CM was protocol prohibition.
      The most common medications discontinued were herbal, proton pump inhibitors,
      selective serotonin reuptake inhibitor anti-depressants, and non-steroidal anti
      inflammatory drugs.

PMID- 22962562
TI  - Heterogeneity of p53-pathway Protein Expression in Chemosensitive Chronic
      Lymphocytic Leukemia: A Pilot Study.
AB  - The presence of p53-pathway dysfunction in chronic lymphocytic leukemia (CLL) can
      be used to identify patients with chemotherapy-refractory disease. Therapeutic
      responses are known to vary between patients with chemosensitive CLL and may
      relate to differences in p53-pathway activity. We hypothesized that the magnitude
      or type of p53-pathway protein expression is heterogeneous in patients with
      chemosensitive disease and could associate with white cell responses. In this
      pilot study, changes in p53 and its transcriptional targets, p21/waf1 and MDM2
      were analyzed by immunoblotting and densitometry in CLL cells from 10 patients
      immediately prior to the start of chemotherapy, and after culture for 24 hours
      (h) with fludarabine (n=7) or chlorambucil (n=3). The in vitro response was also
      compared to that in vivo in circulating cells pre-treatment, and at 24h and 96h
      of chemotherapy. Disease responses were evident in all patients after the first
      treatment-cycle. Significant p53 induction was observed in CLL cells treated in
      vitro and in vivo. Greater heterogeneity in the expression-intensity was observed
      in vivo (sigma2=45.15) than in vitro (sigma2=1.33) and the results failed to
      correlate (r(2)=0.18, p=0.22). p21/waf1 and MDM2 expression-profiles were also
      dissimilar in vitro and in vivo. Higher in vivo (but not in vitro) responses
      associated with changes in white cell count (p=0.026). Thus, heterogeneity of p53
      pathway activity exists in chemosensitive CLL; in unselected patients, in vivo
      changes do not correlate with those in vitro, but may associate with post
      treatment white cell responses.

PMID- 22962563
TI  - Intercellular synchronization of diffusively coupled Ca(2+) oscillators.
AB  - We examine the synchrony in the dynamics of localized [Ca(2 + )](i) oscillations
      among a group of cells exhibiting such complex Ca(2 + ) oscillations, connected
      in the form of long chain, via diffusing coupling where cytosolic Ca(2 + ) and
      inositol 1,4,5-triphosphate are coupling molecules. Based on our numerical
      results, we could able to identify three regimes, namely desynchronized,
      transition and synchronized regimes in the (T - k(e)) (time period-coupling
      constant) and (A - k(e)) (amplitude-coupling constant) spaces which are supported
      by phase plots (Deltaphi verses time) and recurrence plots, respectively. We
      further show the increase of synchronization among the cells as the number of
      coupling molecules increases in the (T - k(e)) and (A - k(e)) spaces.

PMID- 22962564
TI  - Migraine and genetic polymorphisms: an overview.
AB  - The relationship between genetic polymorphisms and migraine as a cause of an
      increased risk of thrombotic disorders development is still debated In this
      respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII
      (V34L), beta-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and
      ACE I/D seem to play a determinant role in vascular diseases related to migraine.
      The present review analyzes both the incidence of the above genetic vascular
      mutations in migraineurs and the most re-cent developments related to genetic
      polymorphisms and migraine.

PMID- 22962565
TI  - Epithelial-myoepithelial carcinoma of high grade transformation: the case report
      in the buccal mucosa.
AB  - Epithelial-myoepithelial carcinoma was first described by Danath et al. in 1972
      and is classified as a rare low-grade biphasic neoplasm of the salivary glands.
      This case report presents a male patient who had a lesion in the oral mucosa with
      a history of recurrence of the tumor. The outcome resulted in a profile
      consistent with an epithelial-myoepithelial carcinoma with a high degree of
      transformation. The case highlights the importance of histopathological
      evaluation of oral lesions, which occasionally may not present typical clinical
      aspects of malignant lesion.

PMID- 22962566
TI  - The effect on implant fixation of soaking tricalcium phosphate granules in
      bisphosphonate.
AB  - The use of bone grafting is a well-established way to enhance initial implant
      fixation in situations with reduced bone stock. Ceramic bone substitutes are
      inferior alternatives to autogenous or allogeneic bone graft. Improvement of bone
      graft substitutes is needed. We investigated whether biomechanical implant
      fixation and osseointegration of experimental implant grafted with beta-TCP
      granules (Conduit) could be improved by soaking the beta-TCP granules in
      bisphosphonate (zoledronate). In 10 dogs, a pair of titanium coated implants
      surrounded by a 2.5 mm gap was inserted into the proximal part of each tibia. The
      gap was grafted with beta-TCP granules either soaked with zoledronate or saline.
      At 12 weeks, the implants were evaluated with biomechanical push-out test and
      histomorphometrical analysis. We found that bisphosphonate increased one of the
      three biomechanical parameters, but found no difference in the amount of new bone
      or beta-TCP granules between the two treatment groups. This study indicates that
      local treatment of beta-TCP granules with zoledronate not only has the potential
      to increase implant fixation but also calls for further experimental research in
      order to optimize the dose of zoledronate.

PMID- 22962567
TI  - Acid etching and plasma sterilization fail to improve osseointegration of grit
      blasted titanium implants.
AB  - Interaction between implant surface and surrounding bone influences implant
      fixation. We attempted to improve the bone-implant interaction by 1) adding
      surface micro scale topography by acid etching, and 2) removing surface-adherent
      pro-inflammatory agents by plasma cleaning. Implant fixation was evaluated by
      implant osseointegration and biomechanical fixation.The study consisted of two
      paired animal sub-studies where 10 skeletally mature Labrador dogs were used.
      Grit blasted titanium alloy implants were inserted press fit in each proximal
      tibia. In the first study grit blasted implants were compared with acid etched
      grit blasted implants. In the second study grit blasted implants were compared
      with acid etched grit blasted implants that were further treated with plasma
      sterilization. Implant performance was evaluated by histomorphometrical
      investigation (tissue-to-implant contact, peri-implant tissue density) and
      mechanical push-out testing after four weeks observation time.Neither acid
      etching nor plasma sterilization of the grit blasted implants enhanced
      osseointegration or mechanical fixation in this press-fit canine implant model in
      a statistically significant manner.

PMID- 22962568
TI  - Changes in midbrain pain receptor expression, gait and behavioral sensitivity in
      a rat model of radiculopathy.
AB  - Intervertebral disc herniation may contribute to inflammatory processes that
      associate with radicular pain and motor deficits. Molecular changes at the
      affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been
      documented in rat models of radiculopathy or nerve injury. The objective of this
      study was to evaluate gait and the expression of key pain receptors in the
      midbrain in a rodent model of radiculopathy. Radiculopathy was induced by
      harvesting tail nucleus pulposus (NP) and placing upon the right L5 DRG in rats
      (NP-treated, n=12). Tail NP was discarded in sham-operated animals (n=12).
      Mechanical allodynia, weight-bearing, and gait were evaluated in all animals over
      time. At 1 and 4 weeks after surgery, astrocyte and microglial activation was
      tested in DRG sections. Midbrain sections were similarly evaluated for
      immunoreactivity to serotonin (5HT(2B)), mu-opioid (u-OR), and metabotropic
      glutamate (mGluR4 and 5) receptor antibodies. NP-treated animals placed less
      weight on the affected limb 1 week after surgery and experienced mechanical
      hypersensitivity over the duration of the study. Astroctye activation was
      observed at DRGs only at 4 weeks after surgery. Findings for pain receptors in
      the midbrain of NP-treated rats included an increased expression of 5HT(2B) at 1,
      but not 4 weeks; increased expression of u-OR and mGluR5 at 1 and 4 weeks
      (periaqueductal gray region only); and no changes in expression of mGluR4 at any
      point in this study. These observations provide support for the hypothesis that
      the midbrain responds to DRG injury with a transient change in receptors
      regulating pain responses.

PMID- 22962569
TI  - Tartrate-Resistant Acid Phosphatase 5b is a Useful Serum Marker for Diagnosis and
      Recurrence Detection of Giant Cell Tumor of Bone.
AB  - Serum tartrate-resistant acid phosphatase (TRACP) 5b was investigated for use as
      a marker for diagnosis of giant cell tumor (GCT) of bone and for detection of its
      recurrence.Four patients with GCT of bone who were initially referred to our
      hospital were classified as a primary group. Three patients who had local
      recurrence following curettage were classified as a local recurrence group. Five
      with no recurrence were classified as a no-recurrence group. Eighteen patients
      with primary and metastatic malignant bone tumors were also enrolled in the study
      as a control group. Serum TRACP 5b was measured before the biopsy in all patients
      and was measured periodically after the operation in patients with GCT of bone.
      Student t-tests were used for statistical analyses.TRACP 5b was greater than 1500
      Um/dL in all primary group patients. Mean TRACP 5b values decreased gradually
      with post-operative time, showing lower values until local recurrence. The mean
      value of TRACP 5b of the local recurrence group (753 +/- 68.7 mU/dL) was
      significantly higher than that of the no-recurrence group (340.6 +/- 78.3 mU/dL).
      The mean value of TRACP 5b of the control group (466.9 +/- 130.3 mU/dL) was much
      lower than that of the primary group and markedly lower than that of the local
      recurrence group. However, no significant difference was found between the no
      recurrence group and the control group.Serum TRACP 5b is a useful and convenient
      marker for diagnosing GCT of bone and for predicting its recurrence.

PMID- 22962570
TI  - Cerebral oximetry and cognitive dysfunction in elderly patients undergoing
      surgery for hip fractures: a prospective observational study.
AB  - AIM: This study was conducted to examine perioperative cerebral oximetry changes
      in elderly patients undergoing hip fracture repair and evaluate the correlation
      between regional oxygen saturation (rSO(2)) values, postoperative cognitive
      dysfunction (POCD) and hospital stay. MATERIALS AND METHODS: This prospective
      observational study included 69 patients. Data recorded included demographic
      information, rSO(2) values from baseline until the second postoperative hour and
      Mini Mental State Examination (MMSE) scores preoperatively and on postoperative
      day 7. MMSE score <=23 was considered evidence of cognitive dysfunction.
      Postoperative confusion or agitation, medications administered for postoperative
      agitation, and hospital length of stay were also recorded. Data were analyzed
      with Student's t-test, Pearson's correlation or multiple regression analysis as
      appropriate. RESULTS: Patient age was 74+/-13 years. Baseline left sided rSO(2)
      values were 60+/-10 and increased significantly after intubation. Baseline rSO(2)
      L<50 and <45 was observed in 11.6% and 10.1% of patients respectively.
      Perioperative cerebral desaturation occurred in 40% of patients. MMSE score was
      26.23 +/- 2.77 before surgery and 25.94 +/- 2.52 on postoperative day 7
      (p=0.326). MMSE scores <= 23 were observed preoperatively in 6 and
      postoperatively in 9 patients. Patients with cognitive dysfunction had lower
      preoperative hematocrit, hemoglobin, SpO(2) and rSO(2) values at all times,
      compared to patients who did not. There was no correlation between rSO(2) or POCD
      and hospital stay. Patients with baseline rSO(2) <5 required more medications for
      postoperative agitation. CONCLUSION: Cognitive dysfunction occurs preoperatively
      and postoperatively in elderly patients with hip fractures, and is associated
      with low cerebral rSO(2) values.

PMID- 22962571
TI  - Considering both health-promoting and illness-related factors in assessment of
      health-related quality of life after myocardial infarction.
AB  - The present study addresses factors that contributed to explaining the variance
      in health-related quality of life (HRQOL) one year after myocardial infarction,
      considering both illness-related and health-promoting factors. The aim was to
      elucidate the influence of depression, fatigue, optimism and sense of coherence
      on HRQOL. The sample consisted of 95 persons who had been treated for myocardial
      infarction. Correlation and multiple regression analyses were performed. The
      results showed that depression, fatigue, optimism and sense of coherence
      variables were all correlated with both the physical and the mental dimensions of
      HRQOL. In two multiple regression analyses where the physical component score
      (PCS) and the mental component score (MCS) were the criterion variables, fatigue
      contributed to the explained variance in the PCS (p< 0.001), and both depression
      (p< 0.01) and fatigue (p< 0.01) contributed to explained the variance in the MCS,
      after controlling for age and gender. To conclude, fatigue was the most
      significant variable associated with HRQOL, which was interpreted as having the
      following clinical implication: When a person suffers from post-myocardial
      infarction fatigue, this must be addressed first. Clearly, it is time to take the
      problems of patients who suffer from post-myocardial infarction fatigue
      seriously. It is of vital importance to develop and evaluate fatigue relief
      strategies in cardiovascular nursing and to test them in interventional studies.
      This does not exclude investing in health-promoting factors, e.g. sense of
      coherence, in coronary care interventions. Intervention strategies focusing on
      both illness-related and salutogentic factors may be optimal. This is a question
      for further research.

PMID- 22962572
TI  - An Efficient Computational Framework for the Analysis of Whole Slide Images:
      Application to Follicular Lymphoma Immunohistochemistry.
AB  - Follicular Lymphoma (FL) is one of the most common non-Hodgkin Lymphoma in the
      United States. Diagnosis and grading of FL is based on the review of
      histopathological tissue sections under a microscope and is influenced by human
      factors such as fatigue and reader bias. Computer-aided image analysis tools can
      help improve the accuracy of diagnosis and grading and act as another tool at the
      pathologist's disposal. Our group has been developing algorithms for identifying
      follicles in immunohistochemical images. These algorithms have been tested and
      validated on small images extracted from whole slide images. However, the use of
      these algorithms for analyzing the entire whole slide image requires significant
      changes to the processing methodology since the images are relatively large (on
      the order of 100k * 100k pixels). In this paper we discuss the challenges
      involved in analyzing whole slide images and propose potential computational
      methodologies for addressing these challenges. We discuss the use of parallel
      computing tools on commodity clusters and compare performance of the serial and
      parallel implementations of our approach.

PMID- 22962573
TI  - Mass Screening for Severe Problem Behavior among Infants and Toddlers In Peru.
AB  - INTRODUCTION: Severe behavior problems among people with intellectual and
      developmental disabilities (IDD) are a major barrier to integration in the
      community. Recent research suggests that these behaviors often begin very early
      in life and might be prevented by early identification and intervention (Rojahn,
      Schroeder, & Hoch, 2008). The current paper presents a method of mass screening
      for early signs of severe behavior problems among infants and toddlers in Peru. 
      METHODS: A Parental Concerns Questionnaire (PCQ) which asks 15 questions, each
      related to a risk factor for severe behavior problems, based on past research on
      IDD, was used by veteran parents to interview 341 new parents who had been
      solicited by TV, radio, and public service announcements across the country. Of
      these, 262 were recruited and enrolled in a longitudinal study in which they will
      be followed for 12 months, to see if at-risk children actually will develop
      severe behavior problems. An extensive initial interdisciplinary evaluation was
      given to each child. Consumer satisfaction questionnaires were given to the
      parents as to their attitude toward the screening method.  RESULTS: Data from the
      Interdisciplinary Evaluations of the sample suggest a very high hit rate (96%) by
      the screening instrument (PCQ). Consumer satisfaction was 98%, suggesting that
      the method was tolerated well by parents.  DISCUSSION: The PCQ is a brief and
      efficient method to screen infants and toddlers at risk for severe behavior
      problems. The data also suggest that parents suspect these problems at a very
      early age. Early intervention thus seems a feasible strategy to intervene before
      these problems become deeply ingrained as children develop.

PMID- 22962574
TI  - Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3
      activation in experimental ulcerative colitis.
AB  - BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal
      homeostasis; its breakdown leads to chronic inflammatory pathologies, such as
      inflammatory bowel diseases (IBDs). Although high concentrations of S100A9
      protein and interleukin-6 (IL-6) are found in patients with IBD, the expression
      mechanism of S100A9 in colonic epithelial cells (CECs) remains elusive. We
      investigated the role of IL-6 in S100A9 expression in CECs using a colitis model.
      METHODS: IL-6 and S100A9 expression, signal transducer and activator of
      transcription 3 (STAT3) phosphorylation, and infiltration of immune cells were
      analyzed in mice with dextran sulfate sodium (DSS)-induced colitis. The effects
      of soluble gp130-Fc protein (sgp130Fc) and S100A9 small interfering (si) RNA (si
      S100A9) on DSS-induced colitis were evaluated. The molecular mechanism of S100A9
      expression was investigated in an IL-6-treated Caco-2 cell line using chromatin
      immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly
      in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to
      DSS-treated mice reduced granulocyte infiltration in CECs and induced the down
      regulation of S100A9 and colitis disease activity. Treatment with STAT3
      inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6
      mediated S100A9 expression through STAT3 activation. Moreover, we found that
      phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune
      cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in
      CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in
      the development of colitis.

PMID- 22962575
TI  - Acceptability and effectiveness of the storekeeper-based TB referral system for
      TB suspects in sub-districts of Lilongwe in Malawi.
AB  - BACKGROUND: Early access to tuberculosis diagnosis and treatment remains a
      challenge in developing countries. General use of informal providers such as
      storekeepers is common. The aim of this study was to determine the effectiveness
      and acceptability of a storekeeper-based referral system for TB suspects in urban
      settings of Lilongwe, Malawi. METHODS: The referral system intervention was
      implemented in two sub-districts. This was evaluated using a pre and post
      comparison as well as comparison with a third sub-district designated as the
      control. The intervention included training of storekeepers to detect and refer
      clients with chronic cough using predesigned referral letters along with
      monitoring and supervision. Data from a community based chronic cough survey and
      an audit of health centre records were used to measure its effectiveness. Focus
      group discussions and in-depth interviews were carried out to document
      acceptability of the intervention with the different stakeholders. RESULTS:
      Following the intervention, the mean patient delay appeared lower in the
      intervention than comparison areas (2.14 weeks (SD 5.8) vs 8.8 weeks (SD 15.1)).
      However, after adjusting for confounding variables this difference was not
      significant (p = 0.07). After the intervention the proportion of the population
      diagnosed with smear positive TB in the intervention sites (1.2 per 1000) was
      significantly higher than in the comparison area (0.6 per 1000, p<0.01) even
      after adjusting for sex and age. Qualitative findings suggested that (a) the
      referral letters triggered health workers to ask patients to submit sputum for TB
      diagnosis (b) the approach may be sustainable as the referral role was linked to
      the livelihood of the storekeepers. CONCLUSION: The study suggests that the
      referral system with storekeepers is sustainable and effective in increasing
      smear positive TB case notification. Studies that assess this approach for
      control of other diseases along with collection of specimens by storekeepers or
      similar providers are needed.

PMID- 22962576
TI  - Identification of pro-inflammatory cytokines associated with muscle invasive
      bladder cancer; the roles of IL-5, IL-20, and IL-28A.
AB  - We used gene expression profiling to identify inflammatory cytokines that
      correlate with bladder cancer development. Gene expression profiles of the tissue
      samples were investigated using cDNA microarrays that contained 103 non-muscle
      invasive bladder cancers (NMIBC), 62 muscle invasive bladder cancers (MIBC), 58
      samples of histologically normal-looking surrounding tissues, and 10 normal,
      healthy subjects who served as the control cohort for comparison. We grouped the
      data-sets according to biological characterizations and focused on immune
      response genes with at least 2-fold differential expression in MIBC vs. controls.
      The experimental data-set identified 36 immune-related genes that were
      significantly altered in MIBC samples. In addition, 10 genes were up-regulated
      and 26 genes were down-regulated in MIBC samples compared with the normal
      tissues. Among the 10 up-regulated molecules examined, the capacity for both
      wound-healing migration and invasion was enhanced in response to IL-5, IL-20, and
      IL-28A in bladder cancer cell lines (253J and EJ cells), compared with untreated
      cells. The expression levels of IL-5, IL-20, and IL-28A were increased in
      patients with MIBC. All 3 cytokines and their receptors were produced in bladder
      cancer cell lines, as determined by real-time PCR, immunoblot analysis and
      confocal immunofluorescence. Up-regulation of MMP-2 and MMP-9 was found after IL
      5, IL-20, and IL-28A stimulation in both cell types. Moreover, an EMSA assay
      showed that treatment with IL-5, IL-20, and IL-28A induced activation of the
      transcription factors NF-kappaB and AP-1 that regulate the MMP-9 promoter.
      Finally, activation of MAPK and Jak-Stat signaling was observed after the
      addition of IL-5, IL-20, and IL-28A to bladder cancer cells. This study suggests
      the presence of specific inflammatory cytokine (IL-5, IL-20, and IL-28A)-mediated
      association in bladder cancer development. All 3 cytokines may be important new
      molecular targets for the modulation of migration and invasion in bladder cancer.

PMID- 22962577
TI  - Re-evaluation of the carcinogenic significance of hepatitis B virus integration
      in hepatocarcinogenesis.
AB  - To examine the role of hepatitis B virus (HBV) integration in
      hepatocarcinogenesis, a systematic comparative study of both tumor and their
      corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV
      associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain
      reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across
      all human chromosomes at random, no difference between tumor and non-tumor tissue
      was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in
      close proximity to cancer related genes such as hTERT were found in this study,
      however overall they were rare events. No direct correlation between chromosome
      aberrations and the number of HBV integration events was found using a sensitive
      array-based comparative genomic hybridization (aCGH) assay. However, a positive
      correlation was observed between the status of several tumor suppressor genes
      (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r =
      0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts
      were in the preC/C region and 57% were in the HBV X gene. Strikingly,
      approximately 24% of the integrations examined had a breakpoint in a short 15 nt
      viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene
      insertions were C-terminal truncated, losing their growth-suppressive domain.
      However, the same pattern of X gene C-terminal truncation was found in both tumor
      and non-tumor derived samples. Furthermore, the integrated viral sequences in
      both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A
      mutations. The frequency and patterns of HBV insertions were similar between
      tumor and their adjacent non-tumor samples indicating that the majority of HBV
      DNA integration events are not associated with hepatocarcinogenesis.

PMID- 22962578
TI  - PPAR-gamma regulates carnitine homeostasis and mitochondrial function in a lamb
      model of increased pulmonary blood flow.
AB  - OBJECTIVE: Carnitine homeostasis is disrupted in lambs with endothelial
      dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent
      studies have also indicated that the disruption in carnitine homeostasis
      correlates with a decrease in PPAR-gamma expression in Shunt lambs. Thus, this
      study was carried out to determine if there is a causal link between loss of PPAR
      gamma signaling and carnitine dysfunction, and whether the PPAR-gamma agonist,
      rosiglitazone preserves carnitine homeostasis in Shunt lambs. METHODS AND
      RESULTS: siRNA-mediated PPAR-gamma knockdown significantly reduced carnitine
      palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT)
      protein levels. This decrease in carnitine regulatory proteins resulted in a
      disruption in carnitine homeostasis and induced mitochondrial dysfunction, as
      determined by a reduction in cellular ATP levels. In turn, the decrease in
      cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90
      interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment
      preserved carnitine homeostasis and attenuated the development of mitochondrial
      dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved
      eNOS/Hsp90 interactions and NO signaling. CONCLUSION: Our study indicates that
      PPAR-gamma signaling plays an important role in maintaining mitochondrial
      function through the regulation of carnitine homeostasis both in vitro and in
      vivo. Further, it identifies a new mechanism by which PPAR-gamma regulates NO
      signaling through Hsp90. Thus, PPAR-gamma agonists may have therapeutic potential
      in preventing the endothelial dysfunction in children with increased pulmonary
      blood flow.

PMID- 22962579
TI  - Poly I:C enhances susceptibility to secondary pulmonary infections by gram
      positive bacteria.
AB  - Secondary bacterial pneumonias are a frequent complication of influenza and other
      respiratory viral infections, but the mechanisms underlying viral-induced
      susceptibility to bacterial infections are poorly understood. In particular, it
      is unclear whether the host's response against the viral infection, independent
      of the injury caused by the virus, results in impairment of antibacterial host
      defense. Here, we sought to determine whether the induction of an "antiviral"
      immune state using various viral recognition receptor ligands was sufficient to
      result in decreased ability to combat common bacterial pathogens of the lung.
      Using a mouse model, animals were administered polyinosine-polycytidylic acid
      (poly I:C) or Toll-like 7 ligand (imiquimod or gardiquimod) intranasally,
      followed by intratracheal challenge with Streptococcus pneumoniae. We found that
      animals pre-exposed to poly I:C displayed impaired bacterial clearance and
      increased mortality. Poly I:C-exposed animals also had decreased ability to clear
      methicillin-resistant Staphylococcus aureus. Furthermore, we showed that
      activation of Toll-like receptor (TLR)3 and Retinoic acid inducible gene (RIG
      I)/Cardif pathways, which recognize viral nucleic acids in the form of dsRNA,
      both contribute to poly I:C mediated impairment of bacterial clearance. Finally,
      we determined that poly I:C administration resulted in significant induction of
      type I interferons (IFNs), whereas the elimination of type I IFN signaling
      improved clearance and survival following secondary bacterial pneumonia.
      Collectively, these results indicate that in the lung, poly I:C administration is
      sufficient to impair pulmonary host defense against clinically important gram
      positive bacterial pathogens, which appears to be mediated by type I IFNs.

PMID- 22962581
TI  - Denitrification and anammox in tropical aquaculture settlement ponds: an isotope
      tracer approach for evaluating N2 production.
AB  - Settlement ponds are used to treat aquaculture discharge water by removing
      nutrients through physical (settling) and biological (microbial transformation)
      processes. Nutrient removal through settling has been quantified, however, the
      occurrence of, and potential for microbial nitrogen (N) removal is largely
      unknown in these systems. Therefore, isotope tracer techniques were used to
      measure potential rates of denitrification and anaerobic ammonium oxidation
      (anammox) in the sediment of settlement ponds in tropical aquaculture systems.
      Dinitrogen gas (N(2)) was produced in all ponds, although potential rates were
      low (0-7.07 nmol N cm(-3) h(-1)) relative to other aquatic systems.
      Denitrification was the main driver of N(2) production, with anammox only
      detected in two of the four ponds. No correlations were detected between the
      measured sediment variables (total organic carbon, total nitrogen, iron,
      manganese, sulphur and phosphorous) and denitrification or anammox. Furthermore,
      denitrification was not carbon limited as the addition of particulate organic
      matter (paired t-Test; P = 0.350, n = 3) or methanol (paired t-Test; P = 0.744, n
      = 3) did not stimulate production of N(2). A simple mass balance model showed
      that only 2.5% of added fixed N was removed in the studied settlement ponds
      through the denitrification and anammox processes. It is recommended that
      settlement ponds be used in conjunction with additional technologies (i.e.
      constructed wetlands or biological reactors) to enhance N(2) production and N
      removal from aquaculture wastewater.

PMID- 22962580
TI  - RNA-Seq approach for genetic improvement of meat quality in pig and evolutionary
      insight into the substrate specificity of animal carbonyl reductases.
AB  - Changes in meat quality traits are strongly associated with alterations in
      postmortem metabolism which depend on genetic variations, especially
      nonsynonymous single nucleotide variations (nsSNVs) having critical effects on
      protein structure and function. To selectively identify metabolism-related
      nsSNVs, next-generation transcriptome sequencing (RNA-Seq) was carried out using
      RNAs from porcine liver, which contains a diverse range of metabolic enzymes. The
      multiplex SNV genotyping analysis showed that various metabolism-related genes
      had different nsSNV alleles. Moreover, many nsSNVs were significantly associated
      with multiple meat quality traits. Particularly, ch7:g.22112616A>G SNV was
      identified to create a single amino acid change (Thr/Ala) at the 145th residue of
      H1.3-like protein, very close to the putative 147th threonine phosphorylation
      site, suggesting that the nsSNV may affect multiple meat quality traits by
      affecting the epigenetic regulation of postmortem metabolism-related gene
      expression. Besides, one nonsynonymous variation, probably generated by gene
      duplication, led to a stop signal in porcine testicular carbonyl reductase
      (PTCR), resulting in a C-terminal (E281-A288) deletion. Molecular docking and
      energy minimization calculations indicated that the binding affinity of wild-type
      PTCR to 5alpha-DHT, a C(21)-steroid, was superior to that of C-terminal-deleted
      PTCR or human carbonyl reductase, which was very consistent with experimental
      data, reported previously. Furthermore, P284 was identified as an important
      residue mediating the specific interaction between PTCR and 5alpha-DHT, and
      phylogenetic analysis showed that P284 is an evolutionarily conserved residue
      among animal carbonyl reductases, which suggests that the C-terminal tails of
      these reductases may have evolved under evolutionary pressure to increase the
      substrate specificity for C(21)-steroids and facilitate metabolic adaptation.
      Altogether, our RNA-Seq revealed that selective nsSNVs were associated with meat
      quality traits that could be useful for successful marker-assisted selection in
      pigs and also represents a useful resource to enhance understanding of protein
      folding, substrate specificity, and the evolution of enzymes such as carbonyl
      reductase.

PMID- 22962582
TI  - Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor
      correlates with poor prognosis.
AB  - BACKGROUND: The aim of this study was to identify a biomarker useful in the
      diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT). METHODS: The
      karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was
      determined by standard gene microarray assays, and further validated by a
      quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2
      expression in OMGCT and certain clinicopathological features were analyzed.
      Expression of SALL4, a stem cell marker, was also examined in comparison with
      KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold
      in yolk sac tumors and immature teratomas compared to normal ovarian tissue by
      microarray assays. Overexpression was detected in yolk sac tumors, immature
      teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant
      transformation and mixed ovarian germ cell tumors at both the transcription and
      translation levels. A positive correlation between KPNA2 and SALL4 expression at
      both the transcription level (R = 0.5120, P = 0.0125), and the translation level
      (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was
      positively associated with pathologic type, recurrence and uncontrolled, ascitic
      fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction
      to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was
      found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT
      (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low
      expression patients (88% and 79%, n = 48) were significantly higher than the OS
      and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P =
      0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low
      expression patients (84% and 74%, n = 62) was marginally significantly higher
      than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P =
      0.0647, respectively). CONCLUSIONS: KPNA2 is a potential candidate molecular
      marker and important prognostic marker in OMGCT patients.

PMID- 22962583
TI  - Rising diabetes prevalence among urban-dwelling black South Africans.
AB  - OBJECTIVE: To examine the prevalence of and the association of psychosocial risk
      factors with diabetes in 25-74-year-old black Africans in Cape Town in 2008/09
      and to compare the prevalence with a 1990 study. RESEARCH DESIGN AND METHODS: A
      randomly selected cross-sectional sample had oral glucose tolerance tests. The
      prevalence of diabetes (1998 WHO criteria), other cardiovascular risk factors and
      psychosocial measures, including sense of coherence (SOC), locus of control and
      adverse life events, were determined. The comparison of diabetes prevalence
      between this and a 1990 study used the 1985 WHO diabetes criteria. RESULTS: There
      were 1099 participants, 392 men and 707 women (response rate 86%). The age
      standardised (SEGI) prevalence of diabetes was 13.1% (95% confidence interval
      (CI) 11.0-15.1), impaired glucose tolerance (IGT) 11.2% (9.2-13.1) and impaired
      fasting glycaemia 1.2% (0.6-1.9). Diabetes prevalence peaked in 65-74-year-olds
      (38.6%). Among diabetic participants, 57.9% were known and 38.6% treated. Using
      1985 WHO criteria, age-standardised diabetes prevalence was higher by 53% in
      2008/09 (12.2% (10.2-14.2)) compared to 1990 (8.0% (5.8-10.3)) and IGT by 67%
      (2008/09: 11.7% (9.8-13.7); 1990: 7.0% (4.9-9.1)). In women, older age (OR: 1.05,
      95%CI: 1.03-1.08, p<0.001), diabetes family history (OR: 3.13, 95%CI: 1.92-5.12,
      p<0.001), higher BMI (OR: 1.44, 95%CI: 1.20-1.82, p = 0.001), better quality
      housing (OR: 2.08, 95%CI: 1.01-3.04, p = 0.047) and a lower SOC score (<= 40) was
      positively associated with diabetes (OR: 2.57, 95%CI: 1.37-4.80, p = 0.003).
      Diabetes was not associated with the other psychosocial measures in women or with
      any psychosocial measure in men. Only older age (OR: 1.05, 95%CI: 1.02-1.08, p =
      0.002) and higher BMI (OR: 1.10, 95%CI: 1.04-1.18, p = 0.003) were significantly
      associated with diabetes in men. CONCLUSIONS: The current high prevalence of
      diabetes in urban-dwelling South Africans, and the likelihood of further rises
      given the high rates of IGT and obesity, is concerning. Multi-facetted diabetes
      prevention strategies are essential to address this burden.

PMID- 22962585
TI  - Estimating global "blue carbon" emissions from conversion and degradation of
      vegetated coastal ecosystems.
AB  - Recent attention has focused on the high rates of annual carbon sequestration in
      vegetated coastal ecosystems--marshes, mangroves, and seagrasses--that may be
      lost with habitat destruction ('conversion'). Relatively unappreciated, however,
      is that conversion of these coastal ecosystems also impacts very large pools of
      previously-sequestered carbon. Residing mostly in sediments, this 'blue carbon'
      can be released to the atmosphere when these ecosystems are converted or
      degraded. Here we provide the first global estimates of this impact and evaluate
      its economic implications. Combining the best available data on global area, land
      use conversion rates, and near-surface carbon stocks in each of the three
      ecosystems, using an uncertainty-propagation approach, we estimate that 0.15-1.02
      Pg (billion tons) of carbon dioxide are being released annually, several times
      higher than previous estimates that account only for lost sequestration. These
      emissions are equivalent to 3-19% of those from deforestation globally, and
      result in economic damages of $US 6-42 billion annually. The largest sources of
      uncertainty in these estimates stems from limited certitude in global area and
      rates of land-use conversion, but research is also needed on the fates of
      ecosystem carbon upon conversion. Currently, carbon emissions from the conversion
      of vegetated coastal ecosystems are not included in emissions accounting or
      carbon market protocols, but this analysis suggests they may be disproportionally
      important to both. Although the relevant science supporting these initial
      estimates will need to be refined in coming years, it is clear that policies
      encouraging the sustainable management of coastal ecosystems could significantly
      reduce carbon emissions from the land-use sector, in addition to sustaining the
      well-recognized ecosystem services of coastal habitats.

PMID- 22962584
TI  - Ontological differences in first compared to third trimester human fetal
      placental chorionic stem cells.
AB  - Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold
      promise for use in tissue engineering applications and cell-based therapies, but
      their collection is restricted ethically and technically. In contrast, the
      placenta is a potential source of readily-obtainable stem cells throughout
      pregnancy. In fetal tissues, early gestational stem cells are known to have
      advantageous characteristics over neonatal and adult stem cells. Accordingly, we
      investigated whether early fetal placental chorionic stem cells (e-CSC) were
      physiologically superior to their late gestation fetal chorionic counterparts (l
      CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating
      down the osteogenic, adipogenic and neurogenic pathways, and containing a subset
      of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an
      array of genes expressed in pluripotent stem cells and primordial germ cells,
      including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS,
      NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an
      earlier state of stemness compared to l-CSC, such as smaller size, faster
      kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of
      expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not
      l-CSC, formed embryoid bodies containing cells from the three germ layer
      lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo;
      when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC
      increased bone quality and plasticity; and when applied to a skin wound, e-CSC,
      but not l-CSC, accelerated healing compared to controls. Our results provide
      insight into the ontogeny of the stemness phenotype during fetal development and
      suggest that the more primitive characteristics of early compared to late
      gestation fetal chorionic stem cells may be translationally advantageous.

PMID- 22962586
TI  - Erectile dysfunction and cardiovascular events in diabetic men: a meta-analysis
      of observational studies.
AB  - BACKGROUND: Several studies have shown that erectile dysfunction (ED) influences
      the risk of cardiovascular events (CV events). However, a meta-analysis of the
      overall risk of CV events associated with ED in patients with diabetes has not
      been performed. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE and the
      Cochrane Library for pertinent articles (including references) published between
      1951 and April 22, 2012. English language reports of original observational
      cohort studies and cross-sectional studies were included. Pooled effect estimates
      were obtained by random effects meta-analysis. A total of 3,791 CV events were
      reported in 3 cohort studies and 9 cross-sectional studies (covering 22,586
      subjects). Across the cohort studies, the overall odds ratio (OR) of diabetic men
      with ED versus those without ED was 1.74 (95% confidence interval [CI]: 1.34
      2.27; P<0.001) for CV events and 1.72 (95% CI: 1.5-1.98; P<0.001) for coronary
      heart disease (CHD). The funnel plot, Begg's test, and Egger's test did not show
      evidence of publication bias (all P>0.05). Moreover, meta-regression analysis
      found no relationship between the method used to assess ED (questionnaire or
      interview), mean age, mean hemoglobin A(1c), mean body mass index, or mean
      duration of diabetes and the risk of CV events or CHD. In the cross-sectional
      studies, the OR of diabetic men with ED versus those without ED was 3.39 (95% CI:
      2.58-4.44; P<0.001) for CV events (N = 9), 3.43 (95% CI: 2.46-4.77; P<0.001) for
      CHD (N = 7), and 2.63 (95% CI: 1.41-4.91; P = 0.002) for peripheral vascular
      disease (N = 5). CONCLUSION/SIGNIFICANCE: ED was associated with an increased
      risk of CV events in diabetic patients. Prevention and early detection of
      cardiovascular disease are important in the management of diabetes, especially in
      view of the rapid increase in its prevalence.

PMID- 22962587
TI  - Accumulation of secretory vesicles in the lacrimal gland epithelia is related to
      non-Sjogren's type dry eye in visual display terminal users.
AB  - Previous observations in a rat model of a non-Sjogren's syndrome (non-SS) type of
      dry eye seen in users of visual display terminals (VDT) indicated that secretory
      vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the
      condition. Here, to examine this possibility in humans, we compared the lacrimal
      gland histology and percent SV area in the cytoplasm of acinar epithelial cells
      using light microscopy and transmission electron microscopy, in patients with VDT
      work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal
      controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an
      exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically
      examined in lacrimal gland tissue sections. The lacrimal gland acini were larger
      in the VDT group than in the SS group, and the percent SV area was significantly
      higher in the VDT group than in the normal controls (P = 0.021) or SS group (P =
      0.004). Immunostaining revealed abnormal distributions of VAMP8 in the VDT and SS
      groups. Rab3D was more strongly expressed in the cytoplasm of acinar epithelial
      cells in the VDT group than in that of normal controls. The duration of VDT use
      was significantly longer in the VDT group than in the other groups. These
      findings suggest that excessive SV accumulation in the acinar epithelia may
      contribute to the reduced tear secretion in VDT users.

PMID- 22962588
TI  - Upper limits of normal for serum alanine aminotransferase levels in Chinese Han
      population.
AB  - BACKGROUND AND OBJECTIVES: Serum alanine aminotransferase (ALT) activity is the
      most common tool for the assessment of liver diseases. However, it is not clear
      whether the current normal ALT range really discriminate patients with or without
      liver diseases. The present study was to establish a new normal range of ALT and
      examine its ability to identify patients with hepatitis B or nonalcoholic fatty
      liver disease (NAFLD) in Chinese Han population. METHODS: 53037 adults were
      included in this study from January 1st 2008 to August 31st 2010. The 95th
      percentile of ALT in population with relative low risk factors for liver diseases
      was set as the new upper limits of normal ALT in gender-specific manner. RESULTS:
      The 95(th) percentile levels at low risk factors for liver diseases were achieved
      at 35 U/L for men and 23 U/L for women. The concordance statistics for detection
      were 0.873 (95%CI: 0.865-0.881) for HBV and 0.932 (95%CI: 0.927-0.937) for NAFLD
      in men while 0.857 (95%CI: 0.850-0.864) for HBV and 0.909 (95%CI: 0.903-0.915)
      for NAFLD in women. The median sensitivity of the current used ALT upper limit
      (40 U/L) was 6.6% for HBV and 29.7% for NAFLD and median specificity was 98.7%
      for men and 99.4% for women. Using our new-derived thresholds, the sensitivities
      ranged from 35.3% to 61.1% and the specificities were 94.8% for men and 94.6% for
      women. CONCLUSIONS: Our results suggest that upper limits of ALT 35 U/L for men
      and 23 U/L for women in Chinese Han population. Re-consideration of normal limits
      of ALT should be recommended. TRIAL REGISTRATION: ChiCTR.org ChiCTR-OCS-11001173.

PMID- 22962589
TI  - Calcium input frequency, duration and amplitude differentially modulate the
      relative activation of calcineurin and CaMKII.
AB  - NMDA receptor dependent long-term potentiation (LTP) and long-term depression
      (LTD) are two prominent forms of synaptic plasticity, both of which are triggered
      by post-synaptic calcium elevation. To understand how calcium selectively
      stimulates two opposing processes, we developed a detailed computational model
      and performed simulations with different calcium input frequencies, amplitudes,
      and durations. We show that with a total amount of calcium ions kept constant,
      high frequencies of calcium pulses stimulate calmodulin more efficiently. Calcium
      input activates both calcineurin and Ca(2+)/calmodulin-dependent protein kinase
      II (CaMKII) at all frequencies, but increased frequencies shift the relative
      activation from calcineurin to CaMKII. Irrespective of amplitude and duration of
      the inputs, the total amount of calcium ions injected adjusts the sensitivity of
      the system to calcium input frequencies. At a given frequency, the quantity of
      CaMKII activated is proportional to the total amount of calcium. Thus, an input
      of a small amount of calcium at high frequencies can induce the same activation
      of CaMKII as a larger amount, at lower frequencies. Finally, the extent of
      activation of CaMKII signals with high calcium frequency is further controlled by
      other factors, including the availability of calmodulin, and by the potency of
      phosphatase inhibitors.

PMID- 22962590
TI  - Ribavirin enhances the action of interferon-alpha against hepatitis C virus by
      promoting the p53 activity through the ERK1/2 pathway.
AB  - BACKGROUND/AIMS: Ribavirin significantly enhances the antiviral response of
      interferon-alpha (IFN-alpha) against Hepatitis C virus (HCV), but the underlying
      mechanisms remain poorly understood. Recently, p53 has been identified as an
      important factor involving the suppression of HCV replication in hepatocytes. We,
      therefore, decided to investigate whether and how ribavirin inhibits the
      replication of HCV by promoting the activity of p53. METHODS: HepG2 and HCV
      replicons (JFH1/HepG2) were utilized to study the relationship between ribavirin
      and p53. The effect of ribavirin on cell cycles was analyzed by flow cytometry.
      The activation of p53 and the signaling pathways were determined using
      immunoblotting. By knocking down ERK1/ERK2 and p53 utilizing RNA interference
      strategy, we further assessed the role of ERK1/2 and p53 in the suppression of
      HCV replication by ribavirin in a HCV replicon system. RESULTS: Using HepG2 and
      HCV replicons, we demonstrated that ribavirin caused the cell cycle arrest at G1
      phase and stabilized and activated p53, which was associated with the antiviral
      activity of ribavirin. Compared to either ribavirin or IFN-alpha alone, ribavirin
      plus IFN-alpha resulted in greater p53 activation and HCV suppression. We further
      identified ERK1/2 that linked ribavirin signals to p53 activation. More
      importantly, knockdown of ERK1/2 and p53 partially mitigated the inhibitory
      effects of ribavirin on the HCV replication, indicating that ERK1/2-p53 pathway
      was involved in the anti-HCV effects of ribavirin. CONCLUSION: Ribavirin
      stimulates ERK1/2 and subsequently promotes p53 activity which at least partly
      contributes to the enhanced antiviral response of IFN-alpha plus ribavirin
      against HCV.

PMID- 22962591
TI  - Rapid identification of cell-specific, internalizing RNA aptamers with
      bioinformatics analyses of a cell-based aptamer selection.
AB  - BACKGROUND: The broad applicability of RNA aptamers as cell-specific delivery
      tools for therapeutic reagents depends on the ability to identify aptamer
      sequences that selectively access the cytoplasm of distinct cell types. Towards
      this end, we have developed a novel approach that combines a cell-based selection
      method (cell-internalization SELEX) with high-throughput sequencing (HTS) and
      bioinformatics analyses to rapidly identify cell-specific, internalization
      competent RNA aptamers. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate the
      utility of this approach by enriching for RNA aptamers capable of selective
      internalization into vascular smooth muscle cells (VSMCs). Several rounds of
      positive (VSMCs) and negative (endothelial cells; ECs) selection were performed
      to enrich for aptamer sequences that preferentially internalize into VSMCs. To
      identify candidate RNA aptamer sequences, HTS data from each round of selection
      were analyzed using bioinformatics methods: (1) metrics of selection enrichment;
      and (2) pairwise comparisons of sequence and structural similarity, termed edit
      and tree distance, respectively. Correlation analyses of experimentally validated
      aptamers or rounds revealed that the best cell-specific, internalizing aptamers
      are enriched as a result of the negative selection step performed against ECs.
      CONCLUSIONS AND SIGNIFICANCE: We describe a novel approach that combines cell
      internalization SELEX with HTS and bioinformatics analysis to identify cell
      specific, cell-internalizing RNA aptamers. Our data highlight the importance of
      performing a pre-clear step against a non-target cell in order to select for cell
      specific aptamers. We expect the extended use of this approach to enable the
      identification of aptamers to a multitude of different cell types, thereby
      facilitating the broad development of targeted cell therapies.

PMID- 22962592
TI  - Cytoplasmic plaque formation in hemidesmosome development is dependent on SoxF
      transcription factor function.
AB  - Hemidesmosomes are composed of intricate networks of proteins, that are an
      essential attachment apparatus for the integrity of epithelial tissue. Disruption
      leads to blistering diseases such as epidermolysis bullosa. Members of the Sox
      gene family show dynamic and diverse expression patterns during development and
      mutation analyses in humans and mice provide evidence that they play a remarkable
      variety of roles in development and human disease. Previous studies have
      established that the mouse mutant ragged-opossum (Ra(op)) expresses a dominant
      negative form of the SOX18 transcription factor that interferes with the function
      of wild type SOX18 and of the related SOXF-subgroup proteins SOX7 and -17. Here
      we show that skin and oral mucosa in homozygous Ra(op) mice display extensive
      detachment of epithelium from the underlying mesenchymal tissue, caused by
      tearing of epithelial cells just above the plasma membrane due to hemidesmosome
      disruption. In addition, several hemidesmosome proteins expression were found to
      be dysregulated in the Ra(op) mice. Our data suggest that SOXF transcription
      factors play a role in regulating formation of cytoplasmic plaque protein
      assembly, and that disrupted SOXF function results in epidermolysis bullosa-like
      skin phenotypes.

PMID- 22962593
TI  - A system-level investigation into the mechanisms of Chinese Traditional Medicine:
      Compound Danshen Formula for cardiovascular disease treatment.
AB  - Compound Danshen Formula (CDF) is a widely used Traditional Chinese Medicine
      (TCM) which has been extensively applied in clinical treatment of cardiovascular
      diseases (CVDs). However, the underlying mechanism of clinical administrating CDF
      on CVDs is not clear. In this study, the pharmacological effect of CDF on CVDs
      was analyzed at a systemic point of view. A systems-pharmacological model based
      on chemical, chemogenomics and pharmacological data is developed via network
      reconstruction approach. By using this model, we performed a high-throughput in
      silico screen and obtained a group of compounds from CDF which possess desirable
      pharmacodynamical and pharmacological characteristics. These compounds and the
      corresponding protein targets are further used to search against biological
      databases, such as the compound-target associations, compound-pathway connections
      and disease-target interactions for reconstructing the biologically meaningful
      networks for a TCM formula. This study not only made a contribution to a better
      understanding of the mechanisms of CDF, but also proposed a strategy to develop
      novel TCM candidates at a network pharmacology level.

PMID- 22962594
TI  - Production of organic acids by probiotic lactobacilli can be used to reduce
      pathogen load in poultry.
AB  - Probiotic Lactobacillus can be used to reduce the colonization of pathogenic
      bacteria in food animals, and therefore reduce the risk of foodborne illness to
      consumers. As a model system, we examined the mechanism of protection conferred
      by Lactobacillus species to inhibit C. jejuni growth in vitro and reduce
      colonization in broiler chickens. Possible mechanisms for the reduction of
      pathogens by lactobacilli include: 1) stimulation of adaptive immunity; 2)
      alteration of the cecal microbiome; and, 3) production of inhibitory metabolites,
      such as organic acids. The Lactobacillus species produced lactic acid at
      concentrations sufficient to kill C. jejuni in vitro. We determined that lactic
      acid produced by Lactobacillus disrupted the membrane of C. jejuni, as judged by
      biophotonics. The spectral features obtained using Fourier-transform infrared (FT
      IR) and Raman spectroscopy techniques were used to accurately predict bacterial
      viability and differentiate C. jejuni samples according to lactic acid treatment.
      FT-IR spectral features of C. jejuni and Lactobacillus grown in co-culture
      revealed that the metabolism was dominated by Lactobacillus prior to the killing
      of C. jejuni. Based on our results, the development of future competitive
      exclusion strategies should include the evaluation of organic acid production.

PMID- 22962595
TI  - Expression of TRPV1 channels after nerve injury provides an essential delivery
      tool for neuropathic pain attenuation.
AB  - Increased expression of the transient receptor potential vanilloid 1 (TRPV1)
      channels, following nerve injury, may facilitate the entry of QX-314 into
      nociceptive neurons in order to achieve effective and selective pain relief. In
      this study we hypothesized that the level of QX-314/capsaicin (QX-CAP)--induced
      blockade of nocifensive behavior could be used as an indirect in-vivo measurement
      of functional expression of TRPV1 channels. We used the QX-CAP combination to
      monitor the functional expression of TRPV1 in regenerated neurons after inferior
      alveolar nerve (IAN) transection in rats. We evaluated the effect of this
      combination on pain threshold at different time points after IAN transection by
      analyzing the escape thresholds to mechanical stimulation of lateral mental skin.
      At 2 weeks after IAN transection, there was no QX-CAP mediated block of
      mechanical hyperalgesia, implying that there was no functional expression of
      TRPV1 channels. These results were confirmed immunohistochemically by staining of
      regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel
      expression is an essential necessity for the QX-CAP mediated blockade.
      Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX
      CAP produced a gradual increase in escape threshold, which paralleled the
      increased levels of TRPV1 channels that were detected in regenerated TG neurons.
      Immunohistochemical analysis also revealed that non-myelinated neurons
      regenerated slowly compared to myelinated neurons following IAN transection. We
      also show that TRPV1 expression shifted towards myelinated neurons. Our findings
      suggest that nerve injury modulates the TRPV1 expression pattern in regenerated
      neurons and that the effectiveness of QX-CAP induced blockade depends on the
      availability of functional TRPV1 receptors in regenerated neurons. The results of
      this study also suggest that the QX-CAP based approach can be used as a new
      behavioral tool to detect dynamic changes in TRPV1 expression, in various
      pathological conditions.

PMID- 22962596
TI  - Low-power GaAlAs laser irradiation promotes the proliferation and osteogenic
      differentiation of stem cells via IGF1 and BMP2.
AB  - Low-power laser irradiation (LPLI) has been found to induce various biological
      effects and cellular processes. Also, LPLI has been shown to promote fracture
      repair. Until now, it has been unclear how LPLI promotes bone formation and
      fracture healing. The aim of this study was to investigate the potential
      mechanism of LPLI-mediated enhancement of bone formation using mouse bone marrow
      mesenchymal stem cells (D1 cells). D1 cells were irradiated daily with a gallium
      aluminum-arsenide (GaAlAs) laser at dose of 0, 1, 2, or 4 J/cm(2). The lactate
      dehydrogenase (LDH) assay showed no cytotoxic effects of LPLI on D1 cells, and
      instead, LPLI at 4 J/cm(2) significantly promoted D1 cell proliferation. LPLI
      also enhanced osteogenic differentiation in a dose-dependent manner and
      moderately increased expression of osteogenic markers. The neutralization
      experiments indicated that LPLI regulated insulin-like growth factor 1 (IGF1) and
      bone morphogenetic protein 2 (BMP2) signaling to promote cell proliferation
      and/or osteogenic differentiation. In conclusion, our study suggests that LPLI
      may induce IGF1 expression to promote both the proliferation and osteogenic
      differentiation of D1 cells, whereas it may induce BMP2 expression primarily to
      enhance osteogenic differentiation.

PMID- 22962597
TI  - Distinct modulated pupil function system for real-time imaging of living cells.
AB  - Optical microscopy is one of the most contributive tools for cell biology in the
      past decades. Many microscopic techniques with various functions have been
      developed to date, i.e., phase contrast microscopy, differential interference
      contrast (DIC) microscopy, confocal microscopy, two photon microscopy,
      superresolution microscopy, etc. However, person who is in charge of an
      experiment has to select one of the several microscopic techniques to achieve an
      experimental goal, which makes the biological assay time-consuming and expensive.
      To solve this problem, we have developed a microscopic system with various
      functions in one instrument based on the optical Fourier transformation with a
      lens system for detection while focusing on applicability and user-friendliness
      for biology. The present instrument can arbitrarily modulate the pupil function
      with a micro mirror array on the Fourier plane of the optical pathway for
      detection. We named the present instrument DiMPS (Distinct optical Modulated
      Pupil function System). The DiMPS is compatible with conventional fluorescent
      probes and illumination equipment, and gives us a Fourier-filtered image, a
      pseudo-relief image, and a deep focus depth. Furthermore, DiMPS achieved a
      resolution enhancement (pseudo-superresolution) of 110 nm through the subtraction
      of two images whose pupil functions are independently modulated. In maximum, the
      spatial and temporal resolution was improved to 120 nm and 2 ms, respectively.
      Since the DiMPS is based on relay optics, it can be easily combined with another
      microscopic instrument such as confocal microscope, and provides a method for
      multi-color pseudo-superresolution. Thus, the DiMPS shows great promise as a
      flexible optical microscopy technique in biological research fields.

PMID- 22962598
TI  - A novel MMP-2 inhibitor 3-azidowithaferin A (3-azidoWA) abrogates cancer cell
      invasion and angiogenesis by modulating extracellular Par-4.
AB  - BACKGROUND: Withaferin A, which is a naturally derived steroidal lactone, has
      been found to prevent angiogenesis and metastasis in diverse tumor models. It has
      also been recognized by different groups for prominent anti-carcinogenic roles.
      However, in spite of these studies on withanolides, their detailed anti
      metastatic mechanism of action remained unknown. The current study has poised to
      address the machinery involved in invasion regulation by stable derivative of
      Withaferin A, 3-azido Withaferin A (3-azidoWA) in human cervical HeLa and
      prostate PC-3 cells. METHODS AND PRINCIPAL FINDINGS: Sub-toxic concentration of 3
      azidowithaferin A (3-azido WA) inhibited cancer cell motility and invasion in
      wound healing and Boyden chamber invasion by suppressing MMP-2 activity in
      gelatin zymography and its expression has proved to be a major obstacle in chemo
      sensitivity. We have uncovered a novel mechanism of 3-azidoWA induced
      extracellular pro-apoptotic candidate tumor suppressor Par-4 protein stimulation
      in conditioned media and also noticed a concomitant marked reduction in pAkt and
      pERK signaling by immunoblot analysis. Furthermore, our zymography results
      suggest 3-azidoWA induced MMP-2 inhibition was mediated through secretory Par-4.
      The inhibition of apoptosis by 3-azidoWA could not restore MMP-2 gelatinase
      activity. In addition to this, our in vivo animal experiments data showed 3
      azidoWA abrogated neovascularisation in dose dependent manner in mouse Matrigel
      plug assay. CONCLUSION/SIGNIFICANCE: For this report, we found that 3-azidoWA
      suppressed motility and invasion of HeLa and PC-3 cells in MMP-2 dependent
      manner. Our in vitro result strongly suggests that sub-toxic doses of 3-azidoWA
      enhanced the secretion of extracellular Par-4 that abolished secretory MMP-2
      expression and activity. Depletion of secretory Par-4 restored MMP-2 expression
      and invasion capability of HeLa and PC-3 cells. Further, our findings implied
      that 3-azidoWA attenuated internal phospho-ERK and phospho-Akt expression in a
      dose dependent manner might play a key role in inhibition of mouse angiogenesis
      by 3-azidoWA.

PMID- 22962599
TI  - Institutional review boards' use and understanding of certificates of
      confidentiality.
AB  - Certificates of Confidentiality, issued by agencies of the U.S. government, are
      regarded as an important tool for meeting ethical and legal obligations to
      safeguard research participants' privacy and confidentiality. By shielding
      against forced disclosure of identifying data, Certificates are intended to
      facilitate research on sensitive topics critical to the public's health. Although
      Certificates are potentially applicable to an extensive array of research, their
      full legal effect is unclear, and little is known about stakeholders' views of
      the protections they provide. To begin addressing this challenge, we conducted a
      national survey of institutional review board (IRB) chairs, followed by telephone
      interviews with selected chairs, to learn more about their familiarity with and
      opinions about Certificates; their institutions' use of Certificates; policies
      and practices concerning when Certificates are required or recommended; and the
      role Certificates play in assessments of research risk. Overall, our results
      suggest uncertainty about Certificates among IRB chairs. On most objective
      knowledge questions, most respondents chose the incorrect answer or 'unsure'.
      Among chairs who reported more familiarity with Certificates, composite opinion
      scores calculated based on five survey questions were evenly distributed among
      positive, neutral/middle, and negative views. Further, respondents expressed a
      variety of ideas about the appropriate use of Certificates, what they are
      intended to protect, and their effect on research risk. Nevertheless, chairs who
      participated in our study commonly viewed Certificates as a potentially valuable
      tool, frequently describing them as an 'extra layer' of protection. These
      findings lead to several practical observations concerning the need for more
      stakeholder education about Certificates, consideration of Certificates for a
      broader range of studies, the importance of remaining vigilant and using all
      tools available to protect participants' confidentiality, and the need for
      further empirical investigation of Certificates' effect on researchers and
      research participants.

PMID- 22962600
TI  - Toll-like receptor 4 and high-mobility group box 1 are critical mediators of
      tissue injury and survival in a mouse model for heatstroke.
AB  - The molecular mechanisms that initiate the inflammatory response in heatstroke
      and their relation with tissue injury and lethality are not fully elucidated. We
      examined whether endogenous ligands released by damaged/stressed cells such as
      high-mobility group box 1 (HMGB1) signaling through Toll-like receptor 4 (TLR4)
      may play a pathogenic role in heatstroke. Mutant TLR4-defective (C3H/HeJ) and
      wild type (C3H/HeOuJ) mice were subjected to heat stress in an environmental
      chamber pre-warmed at 43.5  degrees C until their core temperature reached 42.7
      degrees C, which was taken as the onset of heatstroke. The animals were then
      allowed to recover passively at ambient temperature. A sham-heated group served
      as a control. Mutant mice displayed more histological liver damage and higher
      mortality compared with wild type mice (73% vs. 27%, respectively, P<0.001).
      Compared to wild type mice, mutant mice exhibited earlier plasma release of
      markers of systemic inflammation such as HMGB1 (206 +/- 105 vs. 63 +/- 21 ng/ml;
      P = 0.0018 and 209 +/- 100 vs. 46 +/- 32 ng/ml; P<0.0001), IL-6 (144 +/- 40 vs.
      46 +/- 20 pg/ml; P<0.001 and 184 +/- 21 vs. 84 +/- 54 pg/ml; P = 0.04), and IL
      1beta (27 +/- 4 vs. 1.7 +/- 2.3 pg/ml; P<0.0001 at 1 hour). Both strains of mice
      displayed early release of HMGB1 into the circulation upstream of IL-1beta and IL
      6 responses which remained elevated up to 24 h. Specific inhibition of HMGB1
      activity with DNA-binding A Box (600 ug/mouse) protected the mutant mice against
      the lethal effect of heat stress (60% A Box vs. 18% GST protein, P = 0.04). These
      findings suggest a protective role for the TLR4 in the host response to severe
      heat stress. They also suggest that HMGB1 is an early mediator of inflammation,
      tissue injury and lethality in heatstroke in the presence of defective TLR4
      signaling.

PMID- 22962601
TI  - The impact of infection on population health: results of the Ontario burden of
      infectious diseases study.
AB  - BACKGROUND: Evidence-based priority setting is increasingly important for
      rationally distributing scarce health resources and for guiding future health
      research. We sought to quantify the contribution of a wide range of infectious
      diseases to the overall infectious disease burden in a high-income setting.
      METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a
      composite measure comprising premature mortality and reduced functioning due to
      disease, to estimate the burden of 51 infectious diseases and associated
      syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital
      statistics data and disease incidence was estimated from reportable disease,
      healthcare utilization, and cancer registry data, supplemented by local modeling
      studies and national and international epidemiologic studies. The 51 infectious
      agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and
      58,987 incident cases per 100,000 population annually. The most burdensome
      infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia
      coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus,
      Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus.
      The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total
      infectious disease burden, respectively. Marked sex-specific differences in
      disease burden were observed for some pathogens. The main limitations of this
      study were the exclusion of certain infectious diseases due to data availability
      issues, not considering the impact of co-infections and co-morbidity, and the
      inability to assess the burden of milder infections that do not result in
      healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to
      cause a substantial health burden in high-income settings such as Ontario. Most
      of this burden is attributable to a relatively small number of infectious agents,
      for which many effective interventions have been previously identified.
      Therefore, these findings should be used to guide public health policy, planning,
      and research.

PMID- 22962602
TI  - Soil fertilization leads to a decline in between-samples variability of microbial
      community delta13C profiles in a grassland fertilization experiment.
AB  - Gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) was
      used to measure the (13)C/(12)C ratios of PLFAs at natural abundance levels from
      a temperate grassland nitrogen (N) and phosphorus (P) factorial fertilization
      experiment in northern Greece. In each plot two rhizosphere samples were derived
      centred around individual Agrostis capillaris and Prunella vulgaris plants. It
      was hypothesized that the isotopic signal of microbes that preferentially feed on
      recalcitrant litter such as fungi would be modified by fertilization more
      strongly than that of opportunistic microbes using labile C. Microbial community
      delta(13)C was affected by both P and N fertilization regime and plant species
      identity. However, we have been unable to detect significant nutrient effects on
      individual groups of microbes when analyzed separately in contrast to our
      original hypothesis. Intra-treatment variability, as evaluated from Hartley's
      F(max) tests in the five first PCA components axes as well as the size of the
      convex hulls in PCA scoreplots and Mahalanobis distances, was considerably higher
      in the non-fertilized controls. Moreover, a significant relationship was
      established between the change in PLFA abundances and their respective changes in
      delta(13)C for the aggregate of samples and those simultaneously fertilized with
      N and P. We conclude that use of compound specific isotope analysis in the
      absence of labelling represents a valuable and overlooked tool in obtaining an
      insight of microbial community functioning.

PMID- 22962603
TI  - MiR-214 targets beta-catenin pathway to suppress invasion, stem-like traits and
      recurrence of human hepatocellular carcinoma.
AB  - The down-regulation of miR-214 has previously been observed in human
      hepatocellular carcinoma (HCC). Here, we demonstrated the down-regulation of miR
      214 is associated with cell invasion, stem-like traits and early recurrence of
      HCC. Firstly, we validated the suppression of miR-214 in human HCC by real-time
      quantitative RT-PCR (qRT-PCR) in 20 paired tumor and non-tumor liver tissues of
      HCC patients and 10 histologically normal liver tissues from colorectal cancer
      patients with liver metastases. Further qRT-PCR analysis of 50 HCC tissues from
      an independent cohort of HCC patients of whom 29 with early recurrent disease (<2
      years) and 21 with late recurrent disease demonstrated that the suppression of
      miR-214 was significantly more suppressed in samples from HCC patients with early
      recurrent disease compared those from patients with no recurrence. Re-expression
      of miR-214 significantly suppressed the growth of HCC cells in vitro and reduced
      their tumorigenicity in vivo. The enhancer of zeste homologue 2 (EZH2) and beta
      catenin (CTNNB1) was identified as two potential direct downstream targets of miR
      214 through bioinformatics analysis and experimentally validated the miRNA-target
      interactions with a dual-firefly luciferase reporter assay. In corroborate with
      this, both EZH2 and CTNNB1 are found to be significantly overexpressed in human
      HCC biopsies. Since EZH2 can regulate CTNNB1, CTNNB1 can also be an indirect
      target of miR-214 through EZH2. Silencing EZH2 or CTNNB1 expression suppressed
      the growth and invasion of HCC cells and induced E-cadherin (CDH1), known to
      inhibit cell invasion and metastasis. Furthermore, the silencing of miR-214 or
      overexpression of EZH2 increased EpCAM(+) stem-like cells through the activation
      of CTNNB1. Interestingly, the up-regulation of EZH2, CTNNB1 and the down
      regulation of CDH1 in HCC patients correlated with early recurrent disease and
      can be an independent predictor of poor survival. Therefore, miR-214 can directly
      or indirectly target CTNNB1 to modulate the beta-catenin signaling pathway in
      HCC.

PMID- 22962604
TI  - Comparative effect of treadmill exercise on mature BDNF production in control
      versus stroke rats.
AB  - Physical exercise constitutes an innovative strategy to treat deficits associated
      with stroke through the promotion of BDNF-dependent neuroplasticity. However,
      there is no consensus on the optimal intensity/duration of exercise. In addition,
      whether previous stroke changes the effect of exercise on the brain is not known.
      Therefore, the present study compared the effects of a clinically-relevant form
      of exercise on cerebral BDNF levels and localization in control versus stroke
      rats. For this purpose, treadmill exercise (0.3 m/s, 30 min/day, for 7
      consecutive days) was started in rats with a cortical ischemic stroke after
      complete maturation of the lesion or in control rats. Sedentary rats were run in
      parallel. Mature and proBDNF levels were measured on the day following the last
      boot of exercise using Western blotting analysis. Total BDNF levels were
      simultaneously measured using ELISA tests. As compared to the striatum and the
      hippocampus, the cortex was the most responsive region to exercise. In this
      region, exercise resulted in a comparable increase in the production of mature
      BDNF in intact and stroke rats but increased proBDNF levels only in intact rats.
      Importantly, levels of mature BDNF and synaptophysin were strongly correlated.
      These changes in BDNF metabolism coincided with the appearance of intense BDNF
      labeling in the endothelium of cortical vessels. Notably, ELISA tests failed to
      detect changes in BDNF forms. Our results suggest that control beings can be used
      to find conditions of exercise that will result in increased mBDNF levels in
      stroke beings. They also suggest cerebral endothelium as a potential source of
      BDNF after exercise and highlight the importance to specifically measure the
      mature form of BDNF to assess BDNF-dependent plasticity in relation with
      exercise.

PMID- 22962605
TI  - A snapshot of histone modifications within transposable elements in Drosophila
      wild type strains.
AB  - Transposable elements (TEs) are a major source of genetic variability in genomes,
      creating genetic novelty and driving genome evolution. Analysis of sequenced
      genomes has revealed considerable diversity in TE families, copy number, and
      localization between different, closely related species. For instance, although
      the twin species Drosophila melanogaster and D. simulans share the same TE
      families, they display different amounts of TEs. Furthermore, previous analyses
      of wild type derived strains of D. simulans have revealed high polymorphism
      regarding TE copy number within this species. Several factors may influence the
      diversity and abundance of TEs in a genome, including molecular mechanisms such
      as epigenetic factors, which could be a source of variation in TE success. In
      this paper, we present the first analysis of the epigenetic status of four TE
      families (roo, tirant, 412 and F) in seven wild type strains of D. melanogaster
      and D. simulans. Our data shows intra- and inter-specific variations in the
      histone marks that adorn TE copies. Our results demonstrate that the chromatin
      state of common TEs varies among TE families, between closely related species and
      also between wild type strains.

PMID- 22962606
TI  - Identification and sequence analysis of metazoan tRNA 3'-end processing enzymes
      tRNase Zs.
AB  - tRNase Z is the endonuclease responsible for removing the 3'-trailer sequences
      from precursor tRNAs, a prerequisite for the addition of the CCA sequence. It
      occurs in the short (tRNase Z(S)) and long (tRNase Z(L)) forms. Here we report
      the identification and sequence analysis of candidate tRNase Zs from 81 metazoan
      species. We found that the vast majority of deuterostomes, lophotrochozoans and
      lower metazoans have one tRNase Z(S) and one tRNase Z(L) genes, whereas
      ecdysozoans possess only a single tRNase Z(L) gene. Sequence analysis revealed
      that in metazoans, a single nuclear tRNase Z(L) gene is likely to encode both the
      nuclear and mitochondrial forms of tRNA 3'-end processing enzyme through
      mechanisms that include alternative translation initiation from two in-frame
      start codons and alternative splicing. Sequence conservation analysis revealed a
      variant PxKxRN motif, PxPxRG, which is located in the N-terminal region of tRNase
      Z(S)s. We also identified a previously unappreciated motif, AxDx, present in the
      C-terminal region of both tRNase Z(S)s and tRNase Z(L)s. The AxDx motif
      consisting mainly of a very short loop is potentially close enough to form
      hydrogen bonds with the loop containing the PxKxRN or PxPxRG motif. Through
      complementation analysis, we demonstrated the likely functional importance of the
      AxDx motif. In conclusion, our analysis supports the notion that in metazoans a
      single tRNase Z(L) has evolved to participate in both nuclear and mitochondrial
      tRNA 3'-end processing, whereas tRNase Z(S) may have evolved new functions. Our
      analysis also unveils new evolutionarily conserved motifs in tRNase Zs, including
      the C-terminal AxDx motif, which may have functional significance.

PMID- 22962607
TI  - CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer
      cell activation by Toll-like receptor-induced dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) determine the activation and polarization of T
      cells via expression of costimulatory molecules and secretion of cytokines. The
      function of DCs derived from monocytes ex vivo strongly depends on the
      composition of the maturation cocktail used. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed the effect of costimulatory molecule expression and cytokine secretion
      by DCs on T and natural killer (NK) cell activation by conducting a head-to-head
      comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard
      combination of proinflammatory cytokines or IL-10 alone. We could show that TLR
      induced DCs are characterized by a predominance of costimulatory over
      coinhibitory molecules and by high secretion of IL-12p70, but not IL-10.
      Functionally, these signals translated into an increase in IFN-gamma secreting
      Th1 cells and a decrease in regulatory T cells. T cell activation and
      polarization were dependent on IL-12p70 and CD86, but remarkably not on CD80
      signaling. By means of IL-12p70 secretion, only TLR-induced DCs activated NK
      cells. CONCLUSIONS/SIGNIFICANCE: TLR-matured DCs are highly suitable for
      application in immunotherapeutic strategies that rely on strong type 1
      polarization and NK cell activation. Their effects particularly depend on high
      CD86 expression and IL-12p70 secretion.

PMID- 22962608
TI  - Adoptive transfer of siRNA Cblb-silenced CD8+ T lymphocytes augments tumor
      vaccine efficacy in a B16 melanoma model.
AB  - The ubiquitin ligase Cbl-b is an established regulator of T cell immune response
      thresholds. We recently showed that adoptive cell transfer (ACT) of cblb(-/-)
      CD8(+) T cells enhances dendritic cell (DC) immunization-mediated anti-tumor
      effects in immune-competent recipients. However, translation of cblb targeting to
      clinically applicable concepts requires that inhibition of cblb activity be
      transient and reversible. Here we provide experimental evidence that inhibition
      of cblb using chemically synthesized siRNA has such potential. Silencing cblb
      expression by ex vivo siRNA transfection of polyclonal CD8(+) T cells prior to
      ACT increased T cell tumor infiltration, significantly delayed tumor outgrowth,
      and increased survival rates of tumor-bearing mice. As shown by ex vivo recall
      assays, cblb silencing resulted in significant augmentation of intratumoral T
      cell cytokine response. ACT of cblb-silenced polyclonal CD8(+) T cells combined
      with DC-based tumor vaccines predominantly mediated anti-tumor immune responses,
      whereas no signs of autoimmunity could be detected. Importantly, CBLB silencing
      in human CD8(+) T cells mirrored the effects observed for cblb-silenced and cblb
      deficient murine T cells. Our data validate the concept of enhanced anti-tumor
      immunity by repetitive ACT of ex vivo cblb siRNA-silenced hyper-reactive CD8(+) T
      cells as add-on adjuvant therapy to augment the efficacy of existing cancer
      immunotherapy regimens in clinical practice.

PMID- 22962609
TI  - miR-127 protects proximal tubule cells against ischemia/reperfusion:
      identification of kinesin family member 3B as miR-127 target.
AB  - Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute
      kidney injury. Molecular mechanisms underlying proximal tubule response to I/R
      will allow the identification of new therapeutic targets for both clinical
      settings. microRNAs have emerged as crucial and tight regulators of the cellular
      response to insults including hypoxia. Here, we have identified several miRNAs
      involved in the response of the proximal tubule cell to I/R. Microarrays and RT
      PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in
      vitro demonstrated that miR-127 is induced during ischemia and also during
      reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference
      approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia
      Inducible Factor-1alpha (HIF-1alpha) stabilization. Moreover, miR-127 is involved
      in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR
      127 maintains focal adhesion complex assembly and the integrity of tight
      junctions. miR-127 also regulates intracellular trafficking since miR-127
      interference promotes dextran-FITC uptake. In fact, we have identified the
      Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of
      miR-127 in rat proximal tubule cells. In summary, we have described a novel role
      of miR-127 in cell adhesion and its regulation by HIF-1alpha. We also identified
      for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as
      key mediators of proximal epithelial tubule cell response to I/R with potential
      al application in renal ischemic damage management.

PMID- 22962610
TI  - Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA
      mutator mouse.
AB  - Pharmacological agents, such as bezafibrate, that activate peroxisome
      proliferator-activated receptors (PPARs) and PPAR gamma coactivator-1alpha (PGC
      1alpha) pathways have been shown to improve mitochondrial function and energy
      metabolism. The mitochondrial DNA (mtDNA) mutator mouse is a mouse model of aging
      that harbors a proofreading-deficient mtDNA polymerase gamma. These mice develop
      many features of premature aging including hair loss, anemia, osteoporosis,
      sarcopenia and decreased lifespan. They also have increased mtDNA mutations and
      marked mitochondrial dysfunction. We found that mutator mice treated with
      bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging
      like phenotypes. Although we observed an increase in markers of fatty acid
      oxidation in these tissues, we did not detect a generalized increase in
      mitochondrial markers. On the other hand, there were no improvements in muscle
      function or lifespan of the mutator mouse, which we attributed to the rodent
      specific hepatomegaly associated with fibrate treatment. These results showed
      that despite its secondary effects in rodent's liver, bezafibrate was able to
      improve some of the aging phenotypes in the mutator mouse. Because the associated
      hepatomegaly is not observed in primates, long-term bezafibrate treatment in
      humans could have beneficial effects on tissues undergoing chronic bioenergetic
      related degeneration.

PMID- 22962611
TI  - Dietary resveratrol prevents the development of food allergy in mice.
AB  - BACKGROUND: Resveratrol is a bioactive polyphenol enriched in red wine that
      exhibits many beneficial health effects via multiple mechanisms. However, it is
      unclear whether resveratrol is beneficial for the prevention of food allergy.
      This study investigated whether resveratrol inhibited the development of food
      allergy by using a mouse model of the disease. METHODOLOGY/PRINCIPAL FINDINGS:
      Mice fed standard diet or standard diet plus resveratrol were sensitized by
      intragastric administration of ovalbumin (OVA) and mucosal adjuvant cholera toxin
      (CT). Several manifestations of food allergy were then compared between the mice.
      The effects of resveratrol on T cells or dendritic cells were also examined by
      using splenocytes from OVA-specific T cell-receptor (TCR) transgenic DO11.10 mice
      or mouse bone marrow-derived dendritic cells (BMDCs) in vitro. We found that mice
      fed resveratrol showed reduced OVA-specific serum IgE production, anaphylactic
      reaction, and OVA-induced IL-13 and IFN-a production from the mesenteric lymph
      nodes (MLNs) and spleens in comparison to the control mice, following oral
      sensitization with OVA plus CT. In addition, resveratrol inhibited OVA plus CT
      induced IL-4, IL-13, and IFN-a production in splenocytes from DO11.10 mice
      associated with inhibition of GATA-3 and T-bet expression. Furthermore,
      resveratrol suppressed the OVA plus CT-induced CD25 expression and IL-2
      production in DO11.10 mice-splenocytes in association with decreases in CD80 and
      CD86 expression levels. Finally, resveratrol suppressed CT-induced cAMP elevation
      in association with decreases in CD80 and CD86 expression levels in BMDCs.
      CONCLUSIONS/SIGNIFICANCE: Ingestion of resveratrol prevented the development of a
      food allergy model in mice. Given the in vitro findings, resveratrol might do so
      by inhibiting DC maturation and subsequent early T cell activation and
      differentiation via downregulation of CT-induced cAMP activation in mice. These
      results suggest that resveratrol may have potential for prophylaxis against food
      allergy.

PMID- 22962613
TI  - Protein disorder and short conserved motifs in disordered regions are enriched
      near the cytoplasmic side of single-pass transmembrane proteins.
AB  - Intracellular juxtamembrane regions of transmembrane proteins play pivotal roles
      in cell signalling, mediated by protein-protein interactions. Disordered protein
      regions, and short conserved motifs within them, are emerging as key determinants
      of many such interactions. Here, we investigated whether disorder and conserved
      motifs are enriched in the juxtamembrane area of human single-pass transmembrane
      proteins. Conserved motifs were defined as short disordered regions that were
      much more conserved than the adjacent disordered residues. Human single-pass
      proteins had higher mean disorder in their cytoplasmic segments than their
      extracellular parts. Some, but not all, of this effect reflected the shorter
      length of the cytoplasmic tail. A peak of cytoplasmic disorder was seen at around
      30 residues from the membrane. We noted a significant increase in the incidence
      of conserved motifs within the disordered regions at the same location, even
      after correcting for the extent of disorder. We conclude that elevated disorder
      within the cytoplasmic tail of many transmembrane proteins is likely to be
      associated with enrichment for signalling interactions mediated by conserved
      short motifs.

PMID- 22962614
TI  - Characterization of mercury and its risk in Nelson's, Saltmarsh, and Seaside
      Sparrows.
AB  - BACKGROUND: Nelson's, Saltmarsh, and Seaside Sparrows (Ammodramus nelsoni, A.
      caudacutus, and A. maritimus, respectively) depend on marsh and wetland habitats-
      ecosystems in which mercury (Hg) bioavailability is notoriously high. The purpose
      of the present study was to address the potential impact of Hg on these species
      using first primary and breast feathers as non-destructive biomonitoring tools.
      METHODS AND PRINCIPAL FINDINGS: Feathers were sampled from wintering sparrows in
      North Carolina salt marshes (2006-2010). Feather Hg data were used in three risk
      analysis components (1) Threshold Component--examined feather Hg with regard to
      published negative effects thresholds; (2) Hg Dynamics Component--examined Hg in
      sparrows captured multiple times; and (3) Capture Frequency and Survival
      Component--tested for links between Hg and return frequency and survival.
      Threshold Component analyses indicated that Hg concentrations in 42-77% of
      sampled individuals (breast feather n = 879; first primary feather n = 663) were
      within the range associated with decreased reproduction in other avian species.
      Hg Dynamics Component analyses demonstrated that Hg increased between first and
      second captures for Nelson's (n = 9) and Seaside Sparrows (n = 23). Capture
      Frequency and Survival Component analyses detected a negative relationship
      between Hg and capture frequency in Nelson's Sparrows (n = 315). However, MARK
      models detected no effect of Hg on apparent survival in any species. CONCLUSION
      AND SIGNIFICANCE: This study indicates that current Hg exposure places a
      considerable proportion of each population at risk. In particular, 52% of all
      sampled Saltmarsh Sparrows exhibited first primary feather Hg concentrations
      exceeding those associated with a >60% reduction in reproductive success in other
      species. This study reports evidence for net annual bioaccumulation, indicating
      an increased risk in older individuals. These data can be used to inform future
      population assessments and management for these species.

PMID- 22962612
TI  - High-throughput sequencing and characterization of the small RNA transcriptome
      reveal features of novel and conserved microRNAs in Panax ginseng.
AB  - microRNAs (miRNAs) play vital regulatory roles in many organisms through direct
      cleavage of transcripts, translational repression, or chromatin modification.
      Identification of miRNAs has been carried out in various plant species. However,
      no information is available for miRNAs from Panax ginseng, an economically
      significant medicinal plant species. Using the next generation high-throughput
      sequencing technology, we obtained 13,326,328 small RNA reads from the roots,
      stems, leaves and flowers of P. ginseng. Analysis of these small RNAs revealed
      the existence of a large, diverse and highly complicated small RNA population in
      P. ginseng. We identified 73 conserved miRNAs, which could be grouped into 33
      families, and 28 non-conserved ones belonging to 9 families. Characterization of
      P. ginseng miRNA precursors revealed many features, such as production of two
      miRNAs from distinct regions of a precursor, clusters of two precursors in a
      transcript, and generation of miRNAs from both sense and antisense transcripts.
      It suggests the complexity of miRNA production in P. ginseng. Using a
      computational approach, we predicted for the conserved and non-conserved miRNA
      families 99 and 31 target genes, respectively, of which eight were experimentally
      validated. Among all predicted targets, only about 20% are conserved among
      various plant species, whereas the others appear to be non-conserved, indicating
      the diversity of miRNA functions. Consistently, many miRNAs exhibited tissue
      specific expression patterns. Moreover, we identified five dehydration- and ten
      heat-responsive miRNAs and found the existence of a crosstalk among some of the
      stress-responsive miRNAs. Our results provide the first clue to the elucidation
      of miRNA functions in P. ginseng.

PMID- 22962615
TI  - The role of genetic variants of Stromal cell-Derived Factor 1 in pediatric HIV-1
      infection and disease progression.
AB  - Stromal cell-Derived Factor 1 (SDF1) is the natural ligand of CXCR4, the
      coreceptor of HIV-1 X4 viruses. This study investigated the role of the single
      nucleotide polymorphism (SNP) rs1801157 (NM_000609.5:c.*519G>A) of the SDF1 gene
      in the natural history of mother-to-child transmission of HIV-1 and disease
      progression of HIV-1-infected children. The study was conducted in 428 children
      born to HIV-1-seropositive mothers, who had not undergone antiretroviral therapy
      (ART) during pregnancy, and in 120 HIV-1-infected children for whom the end-point
      was the onset of AIDS or the initiation of ART; 16 children developed early AIDS
      (<24 months of life), 13 from 24 to 84 months of age, and 14 had late AIDS (>84
      months). The rs1801157 SNP was not associated with risk of perinatal infection in
      any genetic models tested. By contrast, this SNP influenced disease progression
      in a time-dependent manner. rs1801157 GA heterozygous children had a higher risk
      of late AIDS (HR = 6.3, 95%CI 1.9-20.7, p = 0.002) than children with the
      rs1801157 GG genotype. Children were studied for viral coreceptor usage at birth,
      after 84 months of age and/or at AIDS onset. While R5 viruses using CCR5
      coreceptor were predominant at birth (94%) and at early AIDS (85%), viruses using
      CXCR4 coreceptor emerged during the course of infection and were detected in 49%
      of children older than 84 months and in 62% of late AIDS. The rs1801157 SNP did
      not influence the emergence of R5X4 viruses, but children with the rs1801157 GA
      genotype and R5X4 viruses were at significantly higher risk of late AIDS than
      children with rs1801157 GG genotype (OR = 8.0, 95% CI 1.2-52.2, p = 0.029). Our
      results indicate that the rs1801157 SNP does not influence perinatal infection,
      but impacts disease progression. This effect is time-dependent and linked to the
      coreceptor-usage of viral variants that undergo evolution during the course of
      HIV-1 infection.

PMID- 22962616
TI  - Cesarean section rates and indications in sub-Saharan Africa: a multi-country
      study from Medecins sans Frontieres.
AB  - OBJECTIVES: The World Health Organization considers Cesarean section rates of 5
      15% to be the optimal range for targeted provision of this life saving
      intervention. However, access to safe Cesarean section in resource-limited
      settings is much lower, estimated at 1-2% reported in sub-Saharan Africa. This
      study reports Cesarean sections rates and indications in Democratic Republic of
      Congo, Burundi, and Sierra Leone, and describe the main parameters associated
      with maternal and early neonatal mortality. METHODS: Women undergoing Cesarean
      section from August 1 2010 to January 31 2011 were included in this prospective
      study. Logistic regression was used to model determinants of maternal and early
      neonatal mortality. RESULTS: 1276 women underwent a Cesarean section, giving a
      frequency of 6.2% (range 4.1-16.8%). The most common indications were obstructed
      labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184,
      14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum
      hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015),
      uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P =
      .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with
      maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR
      = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with
      early neonatal death. CONCLUSIONS: This study demonstrates that target Cesarean
      section rates can be achieved in sub-Saharan Africa. Identifying the common
      indications for Cesarean section and associations with mortality can target
      improvements in antenatal services and emergency obstetric care.

PMID- 22962617
TI  - A direct PCR approach to accelerate analyses of human-associated microbial
      communities.
AB  - Since the composition of the human microbiome is highly variable both within and
      between individuals, researchers are increasingly reliant on high-throughput
      molecular approaches to identify linkages between the composition of these
      communities and human health. While new sequencing technologies have made it
      increasingly feasible to analyze large numbers of human-associated samples, the
      extraction of DNA from samples often remains a bottleneck in the process. Here we
      tested a direct PCR approach using the Extract-N-Amp Plant PCR Kit to accelerate
      the 16S rRNA gene-based analyses of human-associated bacterial communities,
      directly comparing this method to a more commonly-used approach whereby DNA is
      first extracted and purified from samples using a series of steps prior to PCR
      amplification. We used both approaches on replicate samples collected from each
      of five body habitats (tongue surface, feces, forehead skin, underarm skin, and
      forearm skin) from four individuals. With the exception of the tongue samples,
      there were few significant differences in the estimates of taxon richness or
      phylogenetic diversity obtained using the two approaches. Perhaps more
      importantly, there were no significant differences between the methods in their
      ability resolve body habitat differences or inter-individual differences in
      bacterial community composition and the estimates of the relative abundances of
      individual taxa were nearly identical with the two methods. Overall, the two
      methods gave very similar results and the direct PCR approach is clearly
      advantageous for many studies exploring the diversity and composition of human
      associated bacterial communities given that large numbers of samples can be
      processed far more quickly and efficiently.

PMID- 22962618
TI  - Secretion of soluble vascular endothelial growth factor receptor 1
      (sVEGFR1/sFlt1) requires Arf1, Arf6, and Rab11 GTPases.
AB  - The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR
      1/sFlt1) is generated by alternative splicing of the FLT1 gene. Secretion of
      sFlt1 from endothelial cells plays an important role in blood vessel sprouting
      and morphogenesis. However, excess sFlt1 secretion is associated with diseases
      such as preeclampsia and chronic kidney disease. To date, the secretory transport
      process involved in the secretion of sFlt1 is poorly understood. In the present
      study, we investigated the itinerary of sFlt1 trafficking along the secretory
      pathway. To understand the timecourse of sFlt1 secretion, endothelial cells
      stably expressing sFlt1 were metabolically radiolabeled with [(35)S]-methionine
      and cysteine. Our results indicate that after initial synthesis the levels of
      secreted [(35)S]-sFlt1 in the extracellular medium peaks at 8 hours. Treatment
      with brefeldin A (BFA), a drug which blocks trafficking between the endoplasmic
      reticulum (ER) and the Golgi complex, inhibited extracellular release of sFlt1
      suggesting that ER to Golgi and intra-Golgi trafficking of sFlt1 are essential
      for its secretion. Furthermore, we show that ectopic expression of dominant
      negative mutant forms of Arf1, Arf6, and Rab11 as well as siRNA-mediated
      knockdown of these GTPases block secretion of sFlt1 during normoxic and hypoxic
      conditions suggesting role for these small GTPases. This work is the first to
      report role of regulatory proteins involved in sFlt1 trafficking along the
      secretory pathway and may provide insights and new molecular targets for the
      modulation of sFlt-1 release during physiological and pathological conditions.

PMID- 22962619
TI  - Reduction of surgical site infections after implementation of a bundle of care.
AB  - BACKGROUND: Surgical Site Infections (SSI) are relatively frequent complications
      after colorectal surgery and are associated with substantial morbidity and
      mortality. OBJECTIVE: Implementing a bundle of care and measuring the effects on
      the SSI rate. DESIGN: Prospective quasi experimental cohort study. METHODS: A
      prospective surveillance for SSI after colorectal surgery was performed in the
      Amphia Hospital, Breda, from January 1, 2008 until January 1, 2012. As part of a
      National patient safety initiative, a bundle of care consisting of 4 elements
      covering the surgical process was introduced in 2009. The elements of the bundle
      were perioperative antibiotic prophylaxis, hair removal before surgery,
      perioperative normothermia and discipline in the operating room. Bundle
      compliance was measured every 3 months in a random sample of surgical procedures.
      RESULTS: Bundle compliance improved significantly from an average of 10% in 2009
      to 60% in 2011. 1537 colorectal procedures were performed during the study period
      and 300 SSI (19.5%) occurred. SSI were associated with a prolonged length of stay
      (mean additional length of stay 18 days) and a significantly higher 6 months
      mortality (Adjusted OR: 2.71, 95% confidence interval 1.76-4.18). Logistic
      regression showed a significant decrease of the SSI rate that paralleled the
      introduction of the bundle. The adjusted Odds ratio of the SSI rate was 36% lower
      in 2011 compared to 2008. CONCLUSION: The implementation of the bundle was
      associated with improved compliance over time and a 36% reduction of the SSI rate
      after adjustment for confounders. This makes the bundle an important tool to
      improve patient safety.

PMID- 22962620
TI  - In vivo screening for secreted proteins that modulate glucose handling identifies
      interleukin-6 family members as potent hypoglycemic agents.
AB  - Diabetes is a disease of abnormal glucose homeostasis characterized by chronic
      hyperglycemia and a broad array of consequent organ damage. Because normal
      glucose homeostasis is maintained by a complex interaction between behavior
      (feeding and physical activity) and metabolic activity that is modulated by inter
      organ signaling through secreted factors, disease modeling in vitro is
      necessarily limited. In contrast, in vivo studies allow complex metabolic
      phenotypes to be studied but present a barrier to high throughput studies. Here
      we present the development of a novel in vivo screening platform that addresses
      this primary limitation of in vivo experimentation. Our platform leverages the
      large secretory capacity of the liver and the hepatocyte transfection technique
      of hydrodynamic tail vein injection to achieve supraphysiologic blood levels of
      secreted proteins. To date, the utility of hydrodynamic transfection has been
      limited by the deleterious impact of the variable transfection efficiency
      inherent to this technique. We overcome this constraint by co-transfection of a
      secreted luciferase cDNA whose product can be easily monitored in the blood of a
      living animal and used as a surrogate marker for transfection efficiency and gene
      expression levels. To demonstrate the utility of our strategy, we screened 248
      secreted proteins for the ability to enhance glucose tolerance. Surprisingly,
      interleukin-6 and several of its family members but not other well-recognized
      insulin sensitizing agents were identified as potent hypoglycemic factors. We
      propose this experimental system as a powerful and flexible in vivo screening
      platform for identifying genes that modulate complex behavioral and metabolic
      phenotypes.

PMID- 22962621
TI  - Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early
      and delayed afterdepolarizations.
AB  - BACKGROUND: Induced pluripotent stem cells (iPSC) provide means to study the
      pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular
      tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly
      caused by mutations in the cardiac ryanodine receptor (RyR2). In this study the
      cellular characteristics of CPVT are investigated and whether the
      electrophysiological features of this mutation can be mimicked using iPSC 
      derived cardiomyocytes (CM). METHODOLOGY/PRINCIPAL FINDINGS: Spontaneously
      beating CMs were differentiated from iPSCs derived from a CPVT patient carrying a
      P2328S mutation in RyR2 and from two healthy controls. Calcium (Ca(2+)) cycling
      and electrophysiological properties were studied by Ca(2+) imaging and patch
      clamp techniques. Monophasic action potential (MAP) recordings and 24h-ECGs of
      CPVT-P2328S patients were analyzed for the presence of afterdepolarizations. We
      found defects in Ca(2+) cycling and electrophysiology in CPVT CMs, reflecting the
      cardiac phenotype observed in the patients. Catecholaminergic stress led to
      abnormal Ca(2+) signaling and induced arrhythmias in CPVT CMs. CPVT CMs also
      displayed reduced sarcoplasmic reticulum (SR) Ca(2+) content, indicating leakage
      of Ca(2+) from the SR. Patch-clamp recordings of CPVT CMs revealed both delayed
      afterdepolarizations (DADs) during spontaneous beating and in response to
      adrenaline and also early afterdepolarizations (EADs) during spontaneous beating,
      recapitulating the changes seen in MAP and 24h-ECG recordings of patients
      carrying the same mutation. CONCLUSIONS/SIGNIFICANCE: This cell model shows
      aberrant Ca(2+) cycling characteristic of CPVT and in addition to DADs it
      displays EADs. This cell model for CPVT provides a platform to study basic
      pathology, to screen drugs, and to optimize drug therapy.

PMID- 22962623
TI  - Where do the eyes really go in the hollow-face illusion?
AB  - The hollow-face illusion refers to the finding that people typically perceive a
      concave (hollow) mask as being convex, despite the presence of binocular
      disparity cues that indicate the contrary. Unlike other illusions of depth,
      recent research has suggested that the eyes tend to converge at perceived, rather
      than actual, depths. However, technical and methodological limitations prevented
      one from knowing whether disparity cues may still have influenced vergence. In
      the current study, we presented participants with virtual normal or hollow masks
      and asked them to fixate the tip of the face's nose until they had indicated
      whether they perceived it as pointing towards or away from them. The results
      showed that the direction of vergence was indeed determined by perceived depth,
      although vergence responses were both somewhat delayed and of smaller amplitude
      (by a factor of about 0.5) for concave than convex masks. These findings
      demonstrate how perceived depth can override disparity cues when it comes to
      vergence, albeit not entirely.

PMID- 22962622
TI  - Early vascular alterations in SLE and RA patients--a step towards understanding
      the associated cardiovascular risk.
AB  - Accelerated atherosclerosis represents a major problem in both systemic lupus
      erythematosus (SLE) and rheumatoid arthritis (RA) patients, and endothelial
      damage is a key feature of atherogenesis. We aimed to assess early endothelial
      changes in SLE and RA female patients (127 SLE and 107 RA) without previous CV
      events. Biomarkers of endothelial cell activation (intercellular adhesion
      molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin
      (TM), and tissue factor (TF)) were measured and endothelial function was assessed
      using peripheral artery tonometry. Reactive hyperemia index (RHI), an indicator
      of microvascular reactivity, and augmentation index (AIx), a measure of arterial
      stiffness, were obtained. In addition, traditional CV risk factors, disease
      activity and medication were determined. Women with SLE displayed higher sICAM-1
      and TM and lower TF levels than women with RA (p = 0.001, p<0.001 and p<0.001,
      respectively). These differences remained significant after controlling for CV
      risk factors and medication. Serum levels of vascular biomarkers were increased
      in active disease and a moderate correlation was observed between sVCAM-1 levels
      and lupus disease activity (rho = 0.246) and between TF levels and RA disease
      activity (rho = 0.301). Although RHI was similar across the groups, AIx was
      higher in lupus as compared to RA (p = 0.04). Also in active SLE, a trend towards
      poorer vasodilation was observed (p = 0.06). In conclusion, women with SLE and RA
      present with distinct patterns of endothelial cell activation biomarkers not
      explained by differences in traditional CV risk factors. Early vascular
      alterations are more pronounced in SLE which is in line with the higher CV risk
      of these patients.

PMID- 22962624
TI  - Thermochemistry of Alane Complexes for Hydrogen Storage: A Theoretical and
      Experimental Investigation.
AB  - Knowledge of the relative stabilities of alane (AlH(3)) complexes with electron
      donors is essential for identifying hydrogen storage materials for vehicular
      applications that can be regenerated by off-board methods; however, almost no
      thermodynamic data are available to make this assessment. To fill this gap, we
      employed the G4(MP2) method to determine heats of formation, entropies, and Gibbs
      free energies of formation for 38 alane complexes with NH(3-n)R(n) (R = Me, Et; n
      = 0-3), pyridine, pyrazine, triethylenediamine (TEDA), quinuclidine, OH(2-n)R(n)
      (R = Me, Et; n = 0-2), dioxane, and tetrahydrofuran (THF). Monomer, bis, and
      selected dimer complex geometries were considered. Using these data, we computed
      the thermodynamics of the key formation and dehydrogenation reactions that would
      occur during hydrogen delivery and alane regeneration, from which trends in
      complex stability were identified. These predictions were tested by synthesizing
      six amine-alane complexes involving trimethylamine, triethylamine,
      dimethylethylamine, TEDA, quinuclidine, and hexamine and obtaining upper limits
      of DeltaG degrees  for their formation from metallic aluminum. Combining these
      computational and experimental results, we establish a criterion for complex
      stability relevant to hydrogen storage that can be used to assess potential
      ligands prior to attempting synthesis of the alane complex. On the basis of this,
      we conclude that only a subset of the tertiary amine complexes considered and
      none of the ether complexes can be successfully formed by direct reaction with
      aluminum and regenerated in an alane-based hydrogen storage system.

PMID- 22962625
TI  - Zirconium((IV)) and Hafnium((IV)) Porphyrin and Phthalocyanine Complexes as New
      Dyes for Solar Cell Devices.
AB  - Metalloporphyrin and metallophthalocyanine dyes ligating Hf(IV) and Zr(IV) ions
      bind to semiconductor oxide surfaces such as TiO(2) via the protruding group IV
      metal ions. The use of oxophylic metal ions with large ionic radii that protrude
      from the macrocycle is a unique mode of attaching chromophores to oxide surfaces
      in the design of dye-sensitized solar cells (DSSCs). Our previous report on the
      structure and physical properties of ternary complexes wherein the Hf(IV) and
      Zr(IV) ions are ligated to both a porphyrinoid and to a defect site on a
      polyoxometalate (POM) represents a model for this new way of binding dyes to
      oxide surfaces. The Zr(IV) and Hf(IV) complexes of 5,10,15,20
      tetraphenylporphyrin (TPP) with two ligated acetates, (TPP)Hf(OAc)(2) and
      (TPP)Zr(OAc)(2), and the corresponding metallophthalocyanine (Pc) diacetate
      complexes, (Pc)Hf(OAc)(2) and (Pc)Zr(OAc)(2), were evaluated as novel dyes for
      the fabrication of dye-sensitized solar cells. Similarly to the ternary complexes
      with the POM, the oxide surface replaces the acetates to affect binding. In DSSCs
      the Zr(IV) phthalocyanine dye performs better than the Zr(IV) porphyrin dye, and
      reaches an overall efficiency of ~ 1.0%. The Hf(IV) dyes are less efficient. The
      photophysical properties of these complexes in solution suggested energetically
      favorable injection of electrons into the conduction band of TiO(2) semiconductor
      nanoparticles, as well as a good band gap match with I(3) (-)/I(-) pair in liquid
      1-butyl-3-methyl imidazolium iodide. The combination of blue absorbing TPP with
      the red absorbing Pc complexes can increase the absorbance of solar light in the
      device; however, the overall conversion efficiency of DSSCs using TiO(2)
      nanoparticles treated with a mixture of both Zr(IV) complexes is comparable, but
      not greater than, the single (Pc)Zr. Thus, surface bound (TPP)Zr increases the
      absorbance in blue region of the spectra, but at the cost of diminished
      absorbance in the red in this DSSC architecture.

PMID- 22962626
TI  - Molecular Dynamics Studies of Dislocations in CdTe Crystals from a New Bond Order
      Potential.
AB  - Cd(1-x)Zn(x)Te (CZT) crystals are the leading semiconductors for radiation
      detection, but their application is limited by the high cost of detector-grade
      materials. High crystal costs primarily result from property nonuniformity that
      causes low manufacturing yield. Although tremendous efforts have been made in the
      past to reduce Te inclusions/precipitates in CZT, this has not resulted in an
      anticipated improvement in material property uniformity. Moreover, it is
      recognized that in addition to Te particles, dislocation cells can also cause
      electric field perturbations and the associated property nonuniformities. Further
      improvement of the material, therefore, requires that dislocations in CZT
      crystals be understood and controlled. Here, we use a recently developed CZT bond
      order potential to perform representative molecular dynamics simulations to study
      configurations, energies, and mobilities of 29 different types of possible
      dislocations in CdTe (i.e., x = 1) crystals. An efficient method to derive
      activation free energies and activation volumes of thermally activated
      dislocation motion will be explored. Our focus gives insight into understanding
      important dislocations in the material and gives guidance toward experimental
      efforts for improving dislocation network structures in CZT crystals.

PMID- 22962627
TI  - Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit
      an Electron-Dense Nanostructured Core.
AB  - Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading
      systems for enabling therapeutic applications of siRNA; however, the structure of
      these systems has not been defined. Here we examine the structure of LNP siRNA
      systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid,
      cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid
      microfluidic mixing process. Techniques employed include cryo-transmission
      electron microscopy, (31)P NMR, membrane fusion assays, density measurements, and
      molecular modeling. The experimental results indicate that these LNP siRNA
      systems have an interior lipid core containing siRNA duplexes complexed to
      cationic lipid and that the interior core also contains phospholipid and
      cholesterol. Consistent with experimental observations, molecular modeling
      calculations indicate that the interior of LNP siRNA systems exhibits a periodic
      structure of aqueous compartments, where some compartments contain siRNA. It is
      concluded that LNP siRNA systems formulated by rapid mixing of an ethanol
      solution of lipid with an aqueous medium containing siRNA exhibit a
      nanostructured core. The results give insight into the mechanism whereby LNP
      siRNA systems are formed, providing an understanding of the high encapsulation
      efficiencies that can be achieved and information on methods of constructing more
      sophisticated LNP systems.

PMID- 22962628
TI  - The impact of clinical nutrition on cancer therapy: a frequently underestimated
      perspective. A complementary approach to cancer patients.

PMID- 22962629
TI  - Socio-economic status and health care utilization in rural Zimbabwe: findings
      from Project Accept (HPTN 043).
AB  - Zimbabwe's HIV epidemic is amongst the worst in the world, and disproportionately
      effects poorer rural areas. Access to almost all health services in Zimbabwe
      includes some form of cost to the client. In recent years, the socio-economic and
      employment status of many Zimbabweans has suffered a serious decline, creating
      additional barriers to HIV treatment and care. We aimed to assess the impact of
      i) socio-economic status (SES) and ii) employment status on the utilization of
      health services in rural Zimbabwe. Data were collected from a random probability
      sample household survey conducted in the Mutoko district of north-western
      Zimbabwe in 2005. We selected variables that described the economic status of the
      respondent, including: being paid to work, employment status, and SES by assets.
      Respondents were also asked about where they most often utilized healthcare when
      they or their family was sick or hurt. Of 2,874 respondents, all forms of
      healthcare tended to be utilized by those of high or medium-high SES (65%),
      including private (65%), church-based (61%), traditional (67%), and other
      providers (66%) (P=0.009). Most respondents of low SES utilized government
      providers (74%) (P=0.009). Seventy-one percent of respondents utilizing health
      services were employed. Government (71%), private (72%), church (71%), community
      based (78%) and other (64%) health services tended to be utilized by employed
      respondents (P=0.000). Only traditional health services were equally utilized by
      unemployed respondents (50%) (P=0.000). A wide range of health providers are
      utilized in rural Zimbabwe. Utilization is strongly associated with SES and
      employment status, particularly for services with user fees, which may act as a
      barrier to HIV treatment and care access. Efforts to improve access in low-SES,
      high HIV-prevalence settings may benefit from the subsidization of the health
      care payment system, efforts to improve SES levels, political reform, and the
      involvement of traditional providers.

PMID- 22962630
TI  - Weight gain in infancy and early childhood is associated with school age body
      mass index but not intelligence and blood pressure in very low birth weight
      children.
AB  - Rates of weight gain in infancy and early childhood can influence later
      neurocognitive, metabolic and cardiovascular health. We studied the relationship
      of weight gain during infancy and early childhood to intelligence quotient (IQ),
      blood pressure (BP) and body mass index (BMI) at age 9 in children born with very
      low birth weight (VLBW). Sixty-five children born prematurely with VLBW were
      followed longitudinally and at 9 years IQ, BP and BMI were measured. The mean
      weight z-scores at birth, neonatal intensive care discharge, 1 year corrected for
      prematurity, 5 and 9 years were -0.17, -2.09, -1.3, -0.68 and 0.06, respectively.
      Weight gain during infancy (discharge to 1 year corrected for prematurity) and
      early childhood (1 year corrected age to 5 years) was expressed as rate of change
      in weight, rate of change in weight z-score and interval change in weight z
      score. In multiple regression analyses that adjusted for race, gender, maternal
      education, antenatal steroids, birth weight z-score, major intracranial lesions
      on ultrasound and chronic lung disease, rates of weight gain in infancy and early
      childhood were predictive of BMI z-score at 9 years, regression coefficients (95%
      confidence intervals); 0.19 (0.02, 0.36) and 0.37 (0.11, 0.63), respectively,
      expressed as change in BMI z-score per 10 g/week weight increase. Rates of weight
      gain were not predictive of systolic BP z-score, Verbal IQ or Performance IQ. In
      VLBW infants, more rapid weight gain during infancy, and especially early
      childhood, is associated with higher BMI at school age. 

PMID- 22962631
TI  - Exploring the borders of European Phragmites within a cosmopolitan genus.
AB  - BACKGROUND AND AIMS: Two Phragmites australis taxa are recognized in Europe: P.
      australis ssp. altissimus, also known as Phragmites isiaca, in the Mediterranean
      region and P. australis in the temperate region. Another taxonomic group in the
      Mediterranean is Phragmites frutescens. European genotypes are diverse
      genetically, cytologically and morphologically, and are related to African,
      Asiatic and American genotypes. We investigated chloroplast DNA (cpDNA) diversity
      in Europe and defined the current borders of the European gene pool. METHODOLOGY:
      We analysed chloroplast variation with parsimony and genetic distance methods,
      and compared it with that of nuclear amplified fragment length polymorphism and
      microsatellites. We also investigated the phenological pattern of 188 genotypes
      collected worldwide in a common garden in Denmark. We assumed that non-flowering
      genotypes could indicate climatic, geographic and/or reproductive barriers to
      dispersal and would have been recorded in the genetic pattern as groups
      genetically isolated from, or within, the European pool. PRINCIPAL RESULTS: The
      European P. australis gene pool extends from North America to the Far East and
      South Africa. However, African and North American genotypes are differentiating
      from the European genotypes. Mediterranean P. australis is genetically different
      from temperate P. australis and shares several similarities with Phragmites
      mauritianus in Africa and Phragmites karka in Asia. Phragmites frutescens shares
      the cpDNA sequences with both these tropical species. Two DNA bands can
      distinguish Mediterranean P. australis from P. frutescens and P. mauritianus and
      from temperate P. australis, and reveal possible hybrids among these species in
      the Mediterranean region. Phenological data confirmed possible gene flow within
      the temperate region of Europe, whereas the Mediterranean genotypes did not set
      inflorescences in Denmark, suggesting reproductive barriers between temperate and
      Mediterranean P. australis. CONCLUSIONS: European P. australis appears as one of
      four main Phragmites groups known in the world. Further research is needed to
      understand the implications of long-distance dispersal at the population level.

PMID- 22962632
TI  - Effects of TGF-beta1 and VEGF-A transgenes on the osteogenic potential of bone
      marrow stromal cells in vitro and in vivo.
AB  - An exogenous supply of growth factors and bioreplaceable scaffolds may help bone
      regeneration. The aim of this study was to examine the effects of TGF-beta1 and
      VEGF-A transgenes on the osteogenic potential of bone marrow stromal cells. Rat
      bone marrow stromal cells were transfected with plasmids encoding mouse TGF-beta1
      and/or VEGF-A complementary DNAs and cultured for up to 28 days. Furthermore,
      collagen scaffolds carrying combinations of the plasmids-transfected cells were
      implanted subcutaneously in rats. The transgenes increased alkaline phosphatase
      activity, enhanced mineralized nodule formation, and elevated osteogenic gene
      expressions in vitro. In vivo, messenger RNA expression of osteogenic genes such
      as BMPs and Runx2 elevated higher by the transgenes. The data indicate that
      exogenous TGF-beta1 and VEGF-A acted synergistically and could induce
      osteoblastic differentiation of bone marrow stromal cells in both cell culture
      and an animal model. The results may provide valuable information to optimize
      protocols for transgene-and-cell-based tissue engineering.

PMID- 22962633
TI  - Three is a crowd in iterated prisoner's dilemmas: experimental evidence on
      reciprocal behavior.
AB  - Reciprocity or conditional cooperation is one of the most prominent mechanisms
      proposed to explain the emergence of cooperation in social dilemmas. Recent
      experimental findings on networked games suggest that conditional cooperation may
      also depend on the previous action of the player. We here report on experiments
      on iterated, multi-player Prisoner's dilemma, on groups of 2 to 5 people. We
      confirm the dependence on the previous step and that memory effects for earlier
      periods are not significant. We show that the behavior of subjects in pairwise
      dilemmas is qualitatively different from the cases with more players; After an
      initial decay, cooperation increases significantly reaching values above 80%. The
      strategy of the players is rather universal as far as their willingness to
      reciprocate cooperation is concerned, whereas there is much diversity in their
      initial propensity to cooperate. Our results indicate that, for cooperation to
      emerge and thrive, three is a crowd.

PMID- 22962634
TI  - The NAD(+)-dependent protein deacetylase activity of SIRT1 is regulated by its
      oligomeric status.
AB  - SIRT1, a NAD(+)-dependent protein deacetylase, is an important regulator in
      cellular stress response and energy metabolism. While the list of SIRT1
      substrates is growing, how the activity of SIRT1 is regulated remains unclear. We
      have previously reported that SIRT1 is activated by phosphorylation at a
      conserved Thr522 residue in response to environmental stress. Here we demonstrate
      that phosphorylation of Thr522 activates SIRT1 through modulation of its
      oligomeric status. We provide evidence that nonphosphorylated SIRT1 protein is
      aggregation-prone in vitro and in cultured cells. Conversely, phosphorylated
      SIRT1 protein is largely in the monomeric state and more active. Our findings
      reveal a novel mechanism for environmental regulation of SIRT1 activity, which
      may have important implications in understanding the molecular mechanism of
      stress response, cell survival, and aging.

PMID- 22962635
TI  - A programmable NOR-based device for transcription profile analysis.
AB  - An autonomous synthetic programmable device that can diagnose a cell's state
      according to predefined markers and produce a corresponding therapeutic output
      may be the basis of future programmable drugs. Motivated to increase diagnosis
      precision, devices that integrate multiple disease markers have been implemented
      based on various molecular tools. As simplicity is key to future in-vivo
      applications, we sought a molecular device that a) integrates multiple inputs
      without requiring pairwise interactions, and b) harnesses only mechanisms that
      cells natively use. Here we show a synthetic NOR-based programmable device,
      operating via a biochemical obstructing approach rather than on a constructive
      approach, capable of differentiating between prokaryotic cell strains based on
      their unique expression profile. To demonstrate our system's strengths we further
      implemented the NOT, OR and AND gates. The device's programmability allows
      context-dependent selection of the inputs being sensed, and of the expressed
      output, thus, holding great promise in future biomedical applications.

PMID- 22962637
TI  - Mental health nurses in general practice - a personal perspective.
AB  - For the past 2 years I have been working as a mental health nurse (MHN) at
      Lyttleton Street Clinic, a general practice clinic in my hometown of Castlemaine
      in Victoria. My background is as a general and mental health nurse, more recently
      in the mental health sector at the Child and Adolescent Mental Health Service. I
      also have postgraduate qualifications in women's health and have recently trained
      as a yoga teacher. My position at the clinic is supported by the national Mental
      Health Nurse Incentive Program (MHNIP). The role has proven to be immensely
      satisfying; I have never felt so useful.

PMID- 22962636
TI  - In situ differentiation of CD8alphaalpha Tau cells from CD4 T cells in peripheral
      lymphoid tissues.
AB  - Mutually exclusive cell fate determination of CD4 helper or CD8 killer T cells
      occurs in the thymus. These T-cell subsets are not believed to redirect other
      lineages. Here we showed that retinoic acid and transforming growth factor-beta1
      promoted the differentiation of CD8alphaalpha T cells from CD4 T cells in a Runx3
      dependent manner. These cells were inferred to belong to immunoregulatory
      populations because subpopulations of CD8alphaalpha+TCRalphabeta T cells are
      known to suppress activated T cells, and mice with Runx3(-/-) T cells showed
      defects during recovery from experimental allergic encephalomyelitis. Our results
      demonstrate that CD4 T cells play fundamental roles in controlling immune
      reactions through promotion and attenuation. We accordingly anticipate that
      clarifying the mechanisms underlying this process will provide insights leading
      to autoimmune and immunodeficiency disease therapies.

PMID- 22962638
TI  - Psychological encounters in general practice.
AB  - In November 2001, Focussed Psychological Strategy (FPS) Medicare item numbers
      were created under the Better Outcomes in Mental Health Care initiative to
      reimburse general practitioners trained in the provision of evidence based
      psychological therapies.

PMID- 22962639
TI  - Motivational interviewing techniques - facilitating behaviour change in the
      general practice setting.
AB  - BACKGROUND: One of the biggest challenges that primary care practitioners face is
      helping people change longstanding behaviours that pose significant health risks.
      OBJECTIVE: To explore current understanding regarding how and why people change,
      and the potential role of motivational interviewing in facilitating behaviour
      change in the general practice setting. DISCUSSION: Research into health related
      behaviour change highlights the importance of motivation, ambivalence and
      resistance. Motivational interviewing is a counselling method that involves
      enhancing a patient's motivation to change by means of four guiding principles,
      represented by the acronym RULE: Resist the righting reflex; Understand the
      patient's own motivations; Listen with empathy; and Empower the patient. Recent
      meta-analyses show that motivational interviewing is effective for decreasing
      alcohol and drug use in adults and adolescents and evidence is accumulating in
      others areas of health including smoking cessation, reducing sexual risk
      behaviours, improving adherence to treatment and medication and diabetes
      management.

PMID- 22962640
TI  - Cognitive behaviour therapy - incorporating therapy into general practice.
AB  - BACKGROUND: Cognitive behaviour therapy is a talking therapy that looks at the
      connections between our emotions, thoughts and behaviours within the context of
      specific circumstances and symptoms. OBJECTIVE: This article describes cognitive
      behaviour therapy, its evidence base and applications. Pathways for further
      training for general practitioners in cognitive behaviour therapy are described.
      DISCUSSION: Cognitive behaviour therapy is an effective treatment for mild to
      moderate depression, generalised anxiety disorder, panic disorder with or without
      agoraphobia, social phobia, post-traumatic stress disorder, and childhood
      depressive and anxiety disorders. At its simplest, it can take the form of an
      exercise prescription, teaching relaxation techniques, assistance with sleep
      hygiene, scheduling pleasurable activities and guiding the patient through
      thought identification and challenge. With some basic training in the area, GPs
      are well placed to provide basic cognitive behaviour therapy treatments,
      particularly to patients at the mild end of the spectrum of mental health
      disease, as they already know their patients well and have a therapeutic alliance
      with them. In some cases, this may be all that is needed; however, patients who
      have more complicated issues or more severe symptoms may require specialist
      psychiatrist or psychologist referral.

PMID- 22962641
TI  - Acceptance and commitment therapy - pathways for general practitioners.
AB  - BACKGROUND: Acceptance and commitment therapy (ACT) focuses on helping patients
      to behave more consistently with their own values and apply mindfulness and
      acceptance skills to their responses to uncontrollable experiences. OBJECTIVE:
      This article presents an overview of ACT, its evidence base and how general
      practitioners can apply ACT consistent practice in the primary care setting. It
      describes pathways for general practitioners to develop further expertise in the
      approach. DISCUSSION: Acceptance and commitment therapy has been associated with
      improved outcomes in patients with chronic pain (comparable to cognitive
      behaviour therapy) and several studies suggest that it may be useful in patients
      with mild to moderate depression. Preliminary evidence of benefit has also been
      shown in the setting of obsessive-compulsive disorder, psychosis, smoking,
      tinnitus, epilepsy and emotionally disordered eating after gastric band surgery.
      Acceptance and commitment therapy starts with a discussion about what the patient
      wants and how they have tried to achieve these aims. Strategies previously used
      to avoid discomfort are discussed. Psychoeducation in ACT involves metaphors,
      stories and experiential exercises to demonstrate the uncontrollability and
      acceptability of much psychological experience. In its final phase, ACT resembles
      traditional behaviour therapy consisting of goal setting and graduated activity
      scheduling toward goals directed by values.

PMID- 22962642
TI  - Problem solving therapy - use and effectiveness in general practice.
AB  - BACKGROUND: Problem solving therapy (PST) is one of the focused psychological
      strategies supported by Medicare for use by appropriately trained general
      practitioners. OBJECTIVE: This article reviews the evidence base for PST and its
      use in the general practice setting. DISCUSSION: Problem solving therapy involves
      patients learning or reactivating problem solving skills. These skills can then
      be applied to specific life problems associated with psychological and somatic
      symptoms. Problem solving therapy is suitable for use in general practice for
      patients experiencing common mental health conditions and has been shown to be as
      effective in the treatment of depression as antidepressants. Problem solving
      therapy involves a series of sequential stages. The clinician assists the patient
      to develop new empowering skills, and then supports them to work through the
      stages of therapy to determine and implement the solution selected by the
      patient. Many experienced GPs will identify their own existing problem solving
      skills. Learning about PST may involve refining and focusing these skills.

PMID- 22962643
TI  - Early and tight glycaemic control - the key to managing type 2 diabetes.
AB  - BACKGROUND: The prevalence of type 2 diabetes is on the rise in Australia. A
      large number of patients with type 2 diabetes do not reach currently recommended
      glycaemic targets. OBJECTIVE: This article looks at how clinical inertia
      contributes to suboptimal glycaemic control in patients with type 2 diabetes,
      describes the 'legacy' effect of early high HbA1c levels and highlights the
      importance of early, tight glycaemic control. DISCUSSION: Early, tight glycaemic
      control in patients with type 2 diabetes has been shown to result in better
      outcomes in terms of micro- and macrovascular disease and mortality even if
      control is relaxed later in the course of the disease. Clinical inertia is one of
      the contributing factors that prevent patients from reaching glycaemic targets. A
      proactive approach to treating type 2 diabetes is recommended: therapy should be
      individualised with early consideration of combination therapy and ongoing
      reinforcement of lifestyle modification messages. In newly diagnosed patients,
      the goal should be to achieve an HbA1c of.

PMID- 22962644
TI  - Cutaneous plaque in a diabetic patient - a case study.
AB  - CASE STUDY: A man, 31 years of age, with type 1 diabetes, presents with a
      slightly pruritic plaque located on the lateral aspect of his left elbow.

PMID- 22962645
TI  - Bone scans.
AB  - This article forms part of our 'Tests and results' series for 2012, which aims to
      provide information about common tests that general practitioners order
      regularly. It considers areas such as indications, what to tell the patient, what
      the test can and cannot tell you and interpretation of results.

PMID- 22962646
TI  - Managing undernutrition in the elderly - prevention is better than cure.
AB  - BACKGROUND: Undernutrition in the elderly is common and can be associated with
      adverse medical consequences, contributing to frailty, morbidity, hospitalisation
      and mortality. OBJECTIVE: This article provides guidelines for screening for
      undernutrition in general practice, and suggests strategies to address
      undernutrition in older patients. DISCUSSION: Screening for undernutrition in
      general practice helps focus time and resources on people at greatest risk. Early
      identification and management of people at risk of undernutrition is important
      because it is difficult to reverse its adverse effects, once established.

PMID- 22962647
TI  - Multiple penile lesions - a case study.
AB  - CASE STUDY: A man, 34 years of age, presented with a 4 day history of painless
      ulcerative lesions on his penis.

PMID- 22962648
TI  - Painful black toe - a case study.
AB  - BACKGROUND: Critical limb ischaemia refers to an advanced form of peripheral
      vascular disease where severe arterial occlusion manifests as chronic ischaemic
      rest pain, nonhealing ulcers and gangrene. Depending on the severity of disease
      and level of occlusion, endovascular revascularisation and vascular surgical
      bypass are indicated to salvage the limb before the inevitable lifesaving choice
      limb amputation. OBJECTIVE: This article illustrates a clinical scenario in
      which, without any intervention, the ischaemic anatomy may dry up and mummify. It
      is a remarkable reminder of the natural history of such events. DISCUSSION:
      Medical management including analgesia, wound care, infection control and
      aggressive modification of atherosclerotic risks factors may contribute to a
      better prognosis. For inoperable cases, pneumatic compression and spinal cord
      stimulation can be considered to relieve symptoms and improve wound healing.

PMID- 22962649
TI  - Neonatal rash - a case study.
AB  - CASE STUDY: An infant, aged 48 days, is brought in by her mother to her doctor
      because of a rash that started during the neonatal period.

PMID- 22962650
TI  - Using a mobile phone application in youth mental health - an evaluation study.
AB  - BACKGROUND: This study evaluates a mobile phone self monitoring tool designed to
      assist paediatricians in assessing and managing youth mental health. METHODS:
      Patients from an adolescent outpatient clinic monitored mental health symptoms
      throughout each day for 2-4 weeks. Paediatricians specialising in adolescent
      health and participants reviewed the collated data displayed online and completed
      quantitative and qualitative feedback. RESULTS: Forty-seven adolescents and six
      paediatricians participated. Completion was high, with 91% of entries completed
      in the first week. Paediatricians found the program helpful for 92% of the
      participants and understood 88% of their patients' functioning better.
      Participants reported the data reflected their actual experiences (88%) and was
      accurate (85%), helpful (65%) and assisted their paediatrician to understand them
      better (77%). Qualitative results supported these findings. DISCUSSION: Self
      monitoring facilitates communication of mental health issues between these
      paediatricians and patients and is a promising tool for the assessment and
      management of mental health problems in young people.

PMID- 22962651
TI  - Changes in the demography of Australia and therefore general practice patient
      populations.
AB  - BACKGROUND: The population of Australia is ageing. We sought to examine the
      impact of this demographic trend on the demography of general practices. METHODS:
      Descriptive statistics of Medicare claims and census data, 1996-2010. RESULTS:
      There have been changes in the demography of general practice patients
      commensurate with changes in the national demography. The proportion of patient
      visits made by those aged >65 years increased from 18.3% to 23.3%, an absolute
      increase of 5% but a relative increase of 27.3%. In contrast, the proportion of
      patient visits to general practices decreased by 16.4% (relative decrease) for
      those aged 0-4 years and 28.9% (relative decrease) for those aged 5-14 years.
      DISCUSSION: As visits for children become a smaller fraction of overall general
      practice visits, the continued comfort level and competency to provide primary
      care of acute and chronic illness in children as well as recognition of abnormal
      development may be affected. To ensure the adequate provision of services to this
      paediatric population, careful ongoing monitoring of general practices, referral
      patterns and comfort levels in the care of children must be undertaken.

PMID- 22962652
TI  - Assessing pathology training needs - results from a survey of general practice
      registrars.
AB  - BACKGROUND: The number of pathology tests ordered by general practitioners is
      rising. Some of this increase may reflect overtesting, overutilisation or
      training deficiency. The aim of this study was to identify the pathology training
      needs of general practice registrars in regards to test ordering and
      interpretation of common conditions found in general practice. METHODS: A
      pathology training needs assessment survey was distributed to 82 South Australian
      general practice registrars. RESULTS: The survey response rate was 55%. Pathology
      training diminishes as participants move through their medical training. General
      practice registrars had most difficulty with test ordering and interpretation in
      the areas of fatigue, menopausal complaints, arthritis and menstrual problems.
      DISCUSSION: These findings will assist those who supervise and support general
      practice registrars in their training. Targeted pathology training in areas
      identified as difficult may assist in reducing healthcare expenditure and improve
      the management of patients' clinical conditions.

PMID- 22962653
TI  - Problem gambling - aetiology, identification and management.
AB  - BACKGROUND: Gambling is a mainstream activity across Australia, with increasing
      accessibility. It is also a significant public health issue, with around 395 000
      Australians experiencing harm from problem gambling. OBJECTIVE: This article
      reviews current evidence relating to the classification and prevalence of problem
      gambling in Australia, why problems develop, and how to assess and manage
      gambling presentations within primary care. DISCUSSION: People affected by
      problem gambling are not a homogenous group in terms of course or onset.
      Screening is important, especially where financial problems are present or when
      there are other conditions that commonly co-occur (such as depression, anxiety,
      substance use disorders and nicotine dependence). Effective management involves a
      nonjudgemental and empathic approach, which may include referral to telephone or
      online services, face-to-face problem gambling programs, financial counselling,
      psychological and pharmacological interventions.

PMID- 22962654
TI  - A is for aphorism - do smart mothers make better diagnoses than poor doctors?
AB  - A core skill to acquire during our medical education is the ability to identify
      the sick child. When presenting cases to my mentors in general practice,
      emergency departments and paediatric services, a recurring question asked of me
      was, 'What does the mother think? How worried is she that this child is really
      sick?' A mother's intuition ranks highly when we are looking to form a diagnosis
      and establish how unwell their child is.

PMID- 22962655
TI  - Bendigo CHS Men's Health Clinic - improving access to primary care.
AB  - This article forms part of our 'Access' series for 2012, profiling organisations
      that provide primary healthcare to groups who are disadvantaged or have
      difficulty accessing mainstream services. The aim of this series is to describe
      the area of need, the innovative strategies that have been developed by specific
      organisations to address this need, and make recommendations to help GPs improve
      access to disadvantaged populations in their own community.

PMID- 22962656
TI  - A new, highly water-soluble, fluorescent turn-on chemodosimeter for direct
      measurement of hydrogen sulfide in biological fluids.
AB  - A new reaction-based fluorescent reporter for H(2)S has been developed based on 8
      aminopyrene-1,3,6-trisulfonate. This reporter shows high selectivity for H(2)S
      over other ions and thiols, and can detect H(2)S directly in serum without
      additives.

PMID- 22962658
TI  - A new peptide-silica bio-inspired stationary phase with an improved approach for
      hydrophilic interaction liquid chromatography.
AB  - A new hydrophilic tripeptide-based organosilica hybrid novel stationary phase has
      been developed for hydrophilic interaction chromatography (HILIC), enabling the
      efficient separation of bioactive polar molecules.

PMID- 22962657
TI  - Identification and imaging of peptides and proteins on Enterococcus faecalis
      biofilms by matrix assisted laser desorption ionization mass spectrometry.
AB  - The heptapeptide ARHPHPH was identified from biofilms and planktonic cultures of
      two different strains of Enterococcus faecalis, V583 and ATCC 29212, using matrix
      assisted laser desorption ionization mass spectrometry (MALDI-MS). ARHPHPH was
      also imaged at the boundary of cocultured, adjacent E. faecalis and Escherichia
      coli (ATCC 25922) biofilms, appearing only on the E. faecalis side. ARHPHPH was
      proteolyzed from kappa-casein, a component in the growth media, by E. faecalis
      microbes. Additionally, top down and bottom up proteomic approaches were combined
      to identify and spatially locate multiple proteins within intact E. faecalis V583
      biofilms by MALDI-MS. The resultant tandem MS data were searched against the
      NCBInr E. faecalis V583 database to identify thirteen cytosolic and membrane
      proteins which have functional association with the cell surface. Two of these
      proteins, enolase and GAPDH, are glycolytic enzymes known to display multiple
      functions in bacterial virulence in related bacterial strains. This work
      illustrates a powerful approach for discovering and localizing multiple peptides
      and proteins within intact biofilms.

PMID- 22962659
TI  - On the aromatic stabilization of benzenoid hydrocarbons.
AB  - A general scheme for estimation of aromatic stabilization energies of benzenoid
      hydrocarbons based on selected topological features has been presented. The
      reactions have been applied to benzene, naphthalene, anthracene, phenanthrene,
      pyrene, tetracene, benz[a]anthracene, chrysene, [4]-helicene, anthanthrene and
      coronene.

PMID- 22962660
TI  - Instantaneous one-pot synthesis of Fe-N-modified graphene as an efficient
      electrocatalyst for the oxygen reduction reaction in acidic solutions.
AB  - We successfully developed a one-pot synthesis method of graphenes modified with
      iron and nitrogen. The modified graphenes functioned as an efficient
      electrocatalyst for the oxygen reduction reaction in acidic solutions with an
      onset-potential of 850 mV vs. RHE in acidic solutions.

PMID- 22962661
TI  - Highly ion-conducting poly(ionic liquid) layers.
AB  - Highly ion-conducting poly(ionic liquid) thin films have been prepared in the
      absence of solvents utilizing a simple 2-step approach comprising pulsed
      plasmachemical deposition of 1-allylimidazole followed by vapour-phase
      quaternization with 1-bromobutane.

PMID- 22962662
TI  - Lewis acid-catalyzed Friedel-Crafts alkylations of 3-hydroxy-2-oxindole: an
      efficient approach to the core structure of azonazine.
AB  - A Lewis acid catalyzed Friedel-Crafts reaction of electron rich aromatics with 3
      alkyl-3-hydroxy-2-oxindole (5) has been developed. The methodology provides a
      straightforward access to the core of azonazine (2) sharing an all-carbon
      quaternary stereocenter at the tetracyclic ring junction.

PMID- 22962663
TI  - Making practical use of the pseudo-element concept: an efficient way to ternary
      intermetalloid clusters by an isoelectronic Pb(-)-Bi combination.
AB  - Syntheses of [K([2.2.2]crypt)](+) salts of binary Pb-Bi Zintl anions and their
      reaction with ZnPh(2) or Ni(cod)(2), yielding ternary intermetalloid Ni-Pb-Bi or
      Zn-Pb-Bi clusters, proved the use of binary precursors with fully isoelectronic
      atoms as an efficient and thus valuable synthetic approach to this class of
      clusters. (207)Pb NMR and ESI mass spectra provided insight into the solution
      behavior of the binary or ternary cages.

PMID- 22962664
TI  - Enantioselectivity in visible light-induced, singlet oxygen [2+4] cycloaddition
      reactions (type II photooxygenations) of 2-pyridones.
AB  - 3-Substituted 2-pyridones were enantioselectively (68-90% ee) converted into the
      respective 3-hydroxypyridine-2,6-diones by a sequence consisting of a template
      mediated type II photooxygenation and an acid-catalysed rearrangement.

PMID- 22962665
TI  - Cathode photoelectrochemical sensing of copper(II) based on analyte-induced
      formation of exciton trapping.
AB  - The analyte-induced formation of exciton trapping leads to the decrease of
      cathode photocurrent of mercapto-capped CdTe quantum dots (QDs), which produces a
      sensitive cathode photoelectrochemical method for selective sensing of trace
      Cu(2+) as the analyte with a linear range from 0.06 to 100 MUM.

PMID- 22962666
TI  - Suppression of matrix ions by N-phosphorylation labeling using matrix-assisted
      laser desorption-ionization time-of-flight mass spectrometry.
AB  - N-Phosphorylation labeling was utilized to analyze small metabolites using matrix
      assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). The incorporation of a neutral phosphoryl group with high gas-phase proton
      affinity not only improved the ionization efficiency of the target molecules, but
      also greatly reduced the matrix background interference.

PMID- 22962668
TI  - Controllable fabrication and broadband near-infrared luminescence of various Ni2+
      activated ZnAl2O4 nanostructures by a single-nozzle electrospinning technique.
AB  - By finely tuning the electrospun parameters (feeding rate of solution, working
      voltage and distance, etc.) and concentration of inorganic salts, various
      ZnAl(2)O(4) nanostructures (nanoparticles, nanonecklaces, nanofibers, nanotubes
      and hollow micromelts) were controllably synthesized by a single-nozzle
      electrospinning technique. The formation mechanisms of different ZnAl(2)O(4)
      nanostructures, including 'oriented attachment' mechanism, 'gas-push' mechanism,
      etc., were proposed to elucidate the morphology of the nanostructures and
      microstructure evolvement process. The morphology and microstructure of calcined
      electrospun nanostructures were considered to be mainly dependent on two factors,
      i.e. concentration of inorganic salts and size of as-prepared electrospun
      nanofibers. Using Ni(2+) ions as activators, broadband near infrared (NIR)
      emission covering 1000-1400 nm peaking at about 1176 nm was detected in Ni(2+)
      doped ZnAl(2)O(4) nanostructures. The broadband NIR emission at around 1.3 MUm
      optical communication window with a long lifetime of ~640 MUs makes Ni(2+)-doped
      ZnAl(2)O(4) nanostructures as a promising candidate for micro/nano-broadband
      optical amplifiers, fibers, etc.

PMID- 22962667
TI  - Advances in functional X-ray imaging techniques and contrast agents.
AB  - X-rays have been used for non-invasive high-resolution imaging of thick
      biological specimens since their discovery in 1895. They are widely used for
      structural imaging of bone, metal implants, and cavities in soft tissue.
      Recently, a number of new contrast methodologies have emerged which are expanding
      X-ray's biomedical applications to functional as well as structural imaging.
      These techniques are promising to dramatically improve our ability to study in
      situ biochemistry and disease pathology. In this review, we discuss how X-ray
      absorption, X-ray fluorescence, and X-ray excited optical luminescence can be
      used for physiological, elemental, and molecular imaging of vasculature, tumors,
      pharmaceutical distribution, and the surface of implants. Imaging of endogenous
      elements, exogenous labels, and analytes detected with optical indicators will be
      discussed.

PMID- 22962669
TI  - An approach to the patient with hirsutism.
AB  - Hirsutism is a common endocrinological complaint. The causes of this complaint
      can vary from dissatisfaction with a normal pattern of hair growth on the one
      hand, to the first clinical manifestation of androgen overproduction by an
      adrenal adenocarcinoma on the other. The purpose of this short review is to
      reexamine the physiology of hair growth in normal women, identify the common
      abnormal patterns, and explore the differential diagnosis associated with each.
      An approach to working through the differential diagnosis will be described, and
      the commonly available treatment modalities for the various forms of hirsutism
      will be examined in terms of risk and benefit. The review is written from the
      point of view of the physician and the most efficient, cost effective, and safe
      clinical approach to the patient with the problem.

PMID- 22962671
TI  - Individualization of therapies for patients with advanced differentiated thyroid
      cancers.

PMID- 22962672
TI  - A piece of the puzzle: what does BRAF status mean in the management of patients
      with papillary thyroid carcinoma?

PMID- 22962678
TI  - Patient information page from The Hormone Foundations. Patient guide to the
      assessment and treatment of hypertriglyceridemia (high triglycerides).

PMID- 22962670
TI  - Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical
      practice guideline.
AB  - OBJECTIVE: The aim was to develop clinical practice guidelines on
      hypertriglyceridemia. PARTICIPANTS: The Task Force included a chair selected by
      The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional
      experts in the field, and a methodologist. The authors received no corporate
      funding or remuneration. CONSENSUS PROCESS: Consensus was guided by systematic
      reviews of evidence, e-mail discussion, conference calls, and one in-person
      meeting. The guidelines were reviewed and approved sequentially by The Endocrine
      Society's CGS and Clinical Affairs Core Committee, members responding to a web
      posting, and The Endocrine Society Council. At each stage, the Task Force
      incorporated changes in response to written comments. CONCLUSIONS: The Task Force
      recommends that the diagnosis of hypertriglyceridemia be based on fasting levels,
      that mild and moderate hypertriglyceridemia (triglycerides of 150-999 mg/dl) be
      diagnosed to aid in the evaluation of cardiovascular risk, and that severe and
      very severe hypertriglyceridemia (triglycerides of > 1000 mg/dl) be considered a
      risk for pancreatitis. The Task Force also recommends that patients with
      hypertriglyceridemia be evaluated for secondary causes of hyperlipidemia and that
      subjects with primary hypertriglyceridemia be evaluated for family history of
      dyslipidemia and cardiovascular disease. The Task Force recommends that the
      treatment goal in patients with moderate hypertriglyceridemia be a non-high
      density lipoprotein cholesterol level in agreement with National Cholesterol
      Education Program Adult Treatment Panel guidelines. The initial treatment should
      be lifestyle therapy; a combination of diet modification and drug therapy may
      also be considered. In patients with severe or very severe hypertriglyceridemia,
      a fibrate should be used as a first-line agent.

PMID- 22962679
TI  - Rosette iron deficiency transcript and microRNA profiling reveals links between
      copper and iron homeostasis in Arabidopsis thaliana.
AB  - Iron (Fe) is an essential plant micronutrient, and its deficiency limits plant
      growth and development on alkaline soils. Under Fe deficiency, plant responses
      include up-regulation of genes involved in Fe uptake from the soil. However,
      little is known about shoot responses to Fe deficiency. Using microarrays to
      probe gene expression in Kas-1 and Tsu-1 ecotypes of Arabidopsis thaliana, and
      comparison with existing Col-0 data, revealed conserved rosette gene expression
      responses to Fe deficiency. Fe-regulated genes included known metal homeostasis
      related genes, and a number of genes of unknown function. Several genes responded
      to Fe deficiency in both roots and rosettes. Fe deficiency led to up-regulation
      of Cu,Zn superoxide dismutase (SOD) genes CSD1 and CSD2, and down-regulation of
      FeSOD genes FSD1 and FSD2. Eight microRNAs were found to respond to Fe
      deficiency. Three of these (miR397a, miR398a, and miR398b/c) are known to
      regulate transcripts of Cu-containing proteins, and were down-regulated by Fe
      deficiency, suggesting that they could be involved in plant adaptation to Fe
      limitation. Indeed, Fe deficiency led to accumulation of Cu in rosettes, prior to
      any detectable decrease in Fe concentration. ccs1 mutants that lack functional
      Cu,ZnSOD proteins were prone to greater oxidative stress under Fe deficiency,
      indicating that increased Cu concentration under Fe limitation has an important
      role in oxidative stress prevention. The present results show that Cu
      accumulation, microRNA regulation, and associated differential expression of Fe
      and CuSOD genes are coordinated responses to Fe limitation.

PMID- 22962680
TI  - Mechanism of phytohormone involvement in feedback regulation of cotton leaf
      senescence induced by potassium deficiency.
AB  - To elucidate the phytohormonal basis of the feedback regulation of leaf
      senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.),
      two cultivars contrasting in sensitivity to K deficiency were self- and
      reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion
      grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock),
      and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling
      stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted
      Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1
      fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also
      decreased the delivery rates of xylem cytokinins [CKs; including the zeatin
      riboside (ZR) and isopentenyl adenosine (iPA) type] by 29-65% and leaf CK
      concentration by 16-57%. The leaf ABA concentration and xylem ABA deliveries were
      consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22
      (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type
      levels were consistently lower in the former than in the latter, irrespective of
      rootstock cultivar or grafting type, indicating that cotton shoot influences the
      levels of ABA and CKs in leaves and xylem sap. Because the scions had little
      influence on phytohormone levels in the roots (rootstocks) of all three types of
      grafts and rootstock xylem sap (collected below the graft union) of Y and
      inverted Y grafts, it appears that the site for basipetal feedback signal(s)
      involved in the regulation of xylem phytohormones is the hypocotyl of cotton
      seedlings. Also, the target of this feedback signal(s) is more likely to be the
      changes in xylem phytohormones within tissues of the hypocotyl rather than the
      export of phytohormones from the roots.

PMID- 22962682
TI  - Control of allergen-induced inflammation and hyperresponsiveness by the
      metalloproteinase ADAMTS-12.
AB  - A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)
      constitute a family of endopeptidases related to matrix metalloproteinases. These
      proteinases have been largely implicated in tissue remodeling associated with
      pathological processes. Among them, ADAMTS12 was identified as an asthma
      associated gene in a human genome screening program. However, its functional
      implication in asthma is not yet documented. The present study aims at
      investigating potential ADAMTS-12 functions in experimental models of allergic
      airways disease. Two different in vivo protocols of allergen-induced airways
      disease were applied to the recently generated Adamts12-deficient mice and
      corresponding wild-type mice. In this study, we provide evidence for a protective
      effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In
      the absence of Adamts12, challenge with different allergens (OVA and house dust
      mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage
      fluid and in lung tissue, along with airway dysfunction assessed by increased
      airway responsiveness following methacholine exposure. Furthermore, mast cell
      counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen
      challenged Adamts12-deficient mice. The present study provides, to our knowledge,
      the first experimental evidence for a contribution of ADAMTS-12 as a key mediator
      in airways disease, interfering with immunological processes leading to
      inflammation and airway hyperresponsiveness.

PMID- 22962683
TI  - Target DNA sequence directly regulates the frequency of activation-induced
      deaminase-dependent mutations.
AB  - Activation-induced deaminase (AID) catalyses class switch recombination (CSR) and
      somatic hypermutation (SHM) in B lymphocytes to enhance Ab diversity. CSR
      involves breaking and rejoining highly repetitive switch (S) regions in the IgH
      (Igh) locus. S regions appear to be preferential targets of AID. To determine
      whether S region sequence per se, independent of Igh cis regulatory elements, can
      influence AID targeting efficiency and mutation frequency, we established a knock
      in mouse model by inserting a core Sgamma1 region into the first intron of proto
      oncogene Bcl6, which is a non-Ig target of SHM. We found that the mutation
      frequency of the inserted Sgamma1 region was dramatically higher than that of the
      adjacent Bcl6 endogenous sequence. Mechanistically, S region-enhanced SHM was
      associated with increased recruitment of AID and RNA polymerase II, together with
      Spt5, albeit to a lesser extent. Our studies demonstrate that target DNA
      sequences influence mutation frequency via regulating AID recruitment. We propose
      that the nucleotide sequence preference may serve as an additional layer of AID
      regulation by restricting its mutagenic activity to specific sequences despite
      the observation that AID has the potential to access the genome widely.

PMID- 22962681
TI  - Hepatic stellate cells undermine the allostimulatory function of liver myeloid
      dendritic cells via STAT3-dependent induction of IDO.
AB  - Hepatic stellate cells (HSCs) are critical for hepatic wound repair and tissue
      remodeling. They also produce cytokines and chemokines that may contribute to the
      maintenance of hepatic immune homeostasis and the inherent tolerogenicity of the
      liver. The functional relationship between HSCs and the professional migratory
      APCs in the liver, that is, dendritic cells (DCs), has not been evaluated. In
      this article, we report that murine liver DCs colocalize with HSCs in vivo under
      normal, steady-state conditions, and cluster with HSCs in vitro. In vitro, HSCs
      secrete high levels of DC chemoattractants, such as MIotaP-1alpha and MCP-1, as
      well as cytokines that modulate DC activation, including TNF-alpha, IL-6, and IL
      1beta. Culture of HSCs with conventional liver myeloid (m) DCs resulted in
      increased IL-6 and IL-10 secretion compared with that of either cell population
      alone. Coculture also resulted in enhanced expression of costimulatory (CD80,
      CD86) and coinhibitory (B7-H1) molecules on mDCs. HSC-induced mDC maturation
      required cell-cell contact and could be blocked, in part, by neutralizing MIotaP
      1alpha or MCP-1. HSC-induced mDC maturation was dependent on activation of STAT3
      in mDCs and, in part, on HSC-secreted IL-6. Despite upregulation of costimulatory
      molecules, mDCs conditioned by HSCs demonstrated impaired ability to induce
      allogeneic T cell proliferation, which was independent of B7-H1, but dependent
      upon HSC-induced STAT3 activation and subsequent upregulation of IDO. In
      conclusion, by promoting IDO expression, HSCs may act as potent regulators of
      liver mDCs and function to maintain hepatic homeostasis and tolerogenicity.

PMID- 22962684
TI  - Autotaxin through lysophosphatidic acid stimulates polarization, motility, and
      transendothelial migration of naive T cells.
AB  - Blood-borne lymphocytes home to lymph nodes by interacting with and crossing high
      endothelial venules (HEVs). The transendothelial migration (TEM) step is poorly
      understood. Autotaxin (ATX) is an ectoenzyme that catalyzes the conversion of
      lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid
      and a close relative of sphingosine 1-phosphate. HEVs produce and secrete ATX
      into the blood. A prior study implicated ATX in the overall homing process, but
      the step in which it functions and its mechanism of action have not been defined.
      In this article, we show that HA130, an inhibitor of the enzymatic activity of
      ATX, slows T cell migration across lymph node HEVs in vivo. Ex vivo, ATX plus LPC
      or LPA itself induces the polarization of mouse naive T cells and stimulates
      their motility on an ICAM-1 substratum. Under physiologic shear conditions in a
      flow chamber, LPA or ATX/LPC strongly enhances TEM of integrin-arrested T cells
      across an endothelial monolayer. HA130 blunts the TEM-promoting activity of ATX,
      paralleling its in vivo effects. T cells possess Mn(+2)-activatable receptors for
      ATX, which are localized at the leading edge of polarized cells. ATX must bind to
      these receptors to elicit a maximal TEM response, providing a mechanism to focus
      the action of LPA onto arrested lymphocytes in flowing blood. Our results
      indicate that LPA produced via ATX facilitates T cell entry into lymph nodes by
      stimulating TEM, substantiating an additional step in the homing cascade. This
      entry role for LPA complements the efflux function of sphingosine 1-phosphate.

PMID- 22962685
TI  - Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9.
AB  - The importance of type I IFN signaling in the innate immune response to viral and
      intracellular pathogens is well established, with an increasing literature
      implicating extracellular bacterial pathogens, including Staphylococcus aureus,
      in this signaling pathway. Airway epithelial cells and especially dendritic cells
      (DCs) contribute to the production of type I IFNs in the lung. We were interested
      in establishing how S. aureus activates the type I IFN cascade in DCs. In vitro
      studies confirmed the rapid uptake of S. aureus by DCs followed promptly by STAT1
      phosphorylation and expression of IFN-beta. Signaling occurred using heat-killed
      organisms and in the absence of PVL and alpha-toxin. Consistent with the
      participation of endosomal and not cytosolic receptors, signaling was
      predominantly mediated by MyD88, TLR9, and IRF1 and blocked by cytochalasin D,
      dynasore, and chloroquine. To determine the role of TLR9 signaling in the
      pathogenesis of S. aureus pneumonia, we infected WT and Tlr9(-/-) mice with MRSA
      USA300. Tlr9(-/-) mice had significantly improved clearance of S. aureus from the
      airways and lung tissue. Ifnar(-/-) mice also had improved clearance. This
      enhanced clearance in Tlr9(-/-) mice was not due to differences in the numbers of
      recruited neutrophils into the airways, but instead correlated with decreased
      induction of TNF. Thus, we identified TLR9 as the critical receptor mediating the
      induction of type I IFN signaling in DCs in response to S. aureus, illustrating
      an additional mechanism through which S. aureus exploits innate immune signaling
      to facilitate infection.

PMID- 22962687
TI  - SB1578, a novel inhibitor of JAK2, FLT3, and c-Fms for the treatment of
      rheumatoid arthritis.
AB  - SB1578 is a novel, orally bioavailable JAK2 inhibitor with specificity for JAK2
      within the JAK family and also potent activity against FLT3 and c-Fms. These
      three tyrosine kinases play a pivotal role in activation of pathways that
      underlie the pathogenesis of rheumatoid arthritis. SB1578 blocks the activation
      of these kinases and their downstream signaling in pertinent cells, leading to
      inhibition of pathological cellular responses. The biochemical and cellular
      activities of SB1578 translate into its high efficacy in two rodent models of
      arthritis. SB1578 not only prevents the onset of arthritis but is also potent in
      treating established disease in collagen-induced arthritis mice with beneficial
      effects on histopathological parameters of bone resorption and cartilage damage.
      SB1578 abrogates the inflammatory response and prevents the infiltration of
      macrophages and neutrophils into affected joints. It also leads to inhibition of
      Ag-presenting dendritic cells and inhibits the autoimmune component of the
      disease. In summary, SB1578 has a unique kinase spectrum, and its pharmacological
      profile provides a strong rationale for the ongoing clinical development in
      autoimmune diseases.

PMID- 22962686
TI  - Dectin-1 and IL-17A suppress murine asthma induced by Aspergillus versicolor but
      not Cladosporium cladosporioides due to differences in beta-glucan surface
      exposure.
AB  - There is considerable evidence supporting a role for mold exposure in the
      pathogenesis and expression of childhood asthma. Aspergillus versicolor and
      Cladosporium cladosporioides are common molds that have been implicated in
      asthma. In a model of mold-induced asthma, mice were repeatedly exposed to either
      A. versicolor or C. cladosporioides spores. The two molds induced distinct
      phenotypes, and this effect was observed in both BALB/c and C57BL/6 strains. C.
      cladosporioides induced robust airway hyperresponsiveness (AHR), eosinophilia,
      and a predominately Th2 response, whereas A. versicolor induced a strong Th17
      response and neutrophilic inflammation, but very mild AHR. Neutralization of IL
      17A resulted in strong AHR and eosinophilic inflammation following A. versicolor
      exposure. In Dectin-1-deficient mice, A. versicolor exposure resulted in markedly
      attenuated IL-17A and robust AHR compared with wild-type mice. In contrast, C.
      cladosporioides induced AHR and eosinophilic inflammation independent of IL-17A
      and Dectin-1. A. versicolor, but not C. cladosporioides, spores had increased
      exposure of beta-glucans on their surface and were able to bind Dectin-1. Thus,
      the host response to C. cladosporioides was IL-17A- and Dectin-1-independent,
      whereas Dectin-1- and IL-17A-dependent pathways were protective against the
      development of asthma after exposure to A. versicolor.

PMID- 22962688
TI  - Human herpesvirus 6 latent infection in patients with glioma.
AB  - The etiology of glioma remains unclear so far. Human herpesvirus 6 (HHV-6) might
      be associated with glioma, but there is no direct evidence to support this. High
      percentages of HHV-6 DNA and protein were detected in tissue from gliomas,
      compared with normal brain tissue. In addition, a strain of HHV-6A was isolated
      from the fluid specimens from glioma cysts. High levels of interleukin 6 (IL-6),
      interleukin 8 (IL-8), tumor necrosis factor alpha, and transforming growth factor
      beta (TGF-beta) were detected in the cyst fluid specimens from HHV-6-positive
      patients with glioma. Furthermore, HHV-6A infection promoted IL-6, IL-8, and TGF
      beta production in astrocyte cultures. Our studies strongly suggest the
      involvement of HHV-6 infection in the pathogenesis of glioma.

PMID- 22962689
TI  - Targeting the Th17 pathway in psoriasis.
AB  - In recent years, the classic paradigm of Th1/Th2 CD4(+) T cell-mediated immunity
      has evolved to include the IL-17A-producing Th17 subset, a distinct
      proinflammatory CD4(+) T cell lineage. Accumulating evidence suggests that IL-17A
      and the Th17 pathway may play an important role in the pathology of psoriasis and
      in other immune-mediated inflammatory diseases. This review summarizes the
      preclinical and clinical evidence implicating Th17 cells in psoriasis and the
      therapeutic approaches, approved or under investigation, to target this pathway
      in psoriasis.

PMID- 22962690
TI  - Niemann-Pick Type C2 protein contributes to the transport of endosomal
      cholesterol to mitochondria without interacting with NPC1.
AB  - Mitochondrial cholesterol is maintained within a narrow range to regulate steroid
      and oxysterol synthesis and to ensure mitochondrial function. Mitochondria
      acquire cholesterol through several pathways from different cellular pools. Here
      we have characterized mitochondrial import of endosomal cholesterol using Chinese
      hamster ovary cells expressing a CYP11A1 fusion protein that converts cholesterol
      to pregnenolone at the mitochondrial inner membrane. RNA interference-mediated
      depletion of the voltage-dependent anion channel 1 in the mitochondrial outer
      membrane or of Niemann-Pick Type C2 (NPC2) in the endosome lumen decreased
      arrival of cholesterol at the mitochondrial inner membrane. Expression of NPC2
      mutants unable to transfer cholesterol to NPC1 still restored mitochondrial
      cholesterol import in NPC2-depleted cells. Transport assays in semi-permeabilized
      cells showed nonvesicular cholesterol trafficking directly from endosomes to
      mitochondria that did not require cytosolic transport proteins but that was
      reduced in the absence of NPC2. Our findings indicate that NPC2 delivers
      cholesterol to the perimeter membrane of late endosomes, where it becomes
      available for transport to mitochondria without requiring NPC1.

PMID- 22962691
TI  - Multiple sequence variants of BRCA2 exon 7 alter splicing regulation.
AB  - BACKGROUND: Exonic variants of unknown biological significance (VUS) identified
      in patients can affect mRNA splicing, either by changing 5' or 3' splice sites or
      by modifying splicing regulatory elements. Bioinformatic predictions of these
      elements are still inaccurate and only few such elements have been functionally
      mapped in BRCA2. We studied the effect on splicing of eight exon 7 VUS, selected
      from the French UMD-BRCA2 mutation database. METHODS: We performed splicing
      minigene assays and analyses of patient RNA. We also developed a pyrosequencing
      based quantitative assay, to measure, in patient RNA, the relative contribution
      of each allele to the production of exon 7-containing transcripts. Moreover, an
      exonic splicing enhancer (ESE)-dependent minigene assay was used to evaluate the
      splicing regulatory properties of wild-type and mutant segments. RESULTS: Six out
      of the eight variants induced splicing defects. In the minigene assay, c.517G>T
      and c.631G>A altered the natural splice sites, c.572A>G created a new 5' splice
      site, and c.520C>T, c.587G>A and c.617C>G induced exon 7 skipping (66%, 25% and
      46%, respectively). Pyrosequencing of patient RNA confirmed these levels of exon
      skipping for c.520C>T and c.617C>G. Results from the ESE-dependent minigene assay
      indicated that c.520C>T and c.587G>A disturb splicing regulatory elements.
      CONCLUSIONS: BRCA2 exon 7 splicing is regulated by multiple exonic elements and
      is sensitive to disease-associated sequence variations. Measurements of allelic
      imbalance in patient-derived RNA and/or quantitative analyses using minigene
      assays provide valuable estimates of the extent of partial splicing defects.
      Assessment of pathogenicity of variants with partial splicing effect awaits
      additional evidence and especially the completion of segregation analyses.

PMID- 22962692
TI  - Dominantly inherited diabetes mellitus caused by GATA6 haploinsufficiency:
      variable intrafamilial presentation.
AB  - GATA6 haploinsufficiency has recently been reported as the most frequent cause of
      neonatal diabetes with pancreatic agenesis. Although all previously reported
      cases represented a de novo mutation with complete agenesis or pronounced
      hypoplasia of the pancreas, in this study we identified a family with a
      dominantly inherited mutation. Unlike previously reported cases, the degree of
      pancreatic hypoplasia and the severity of diabetes varied among members of the
      family, ranging from neonatally lethal diabetes with only a remnant of pancreatic
      tissue to adult-onset diabetes associated with dorsal agenesis of the pancreas.
      These observations further broaden the clinical spectrum of diabetes associated
      with GATA6 haploinsufficiency.

PMID- 22962693
TI  - Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane
      systematic review and meta-analysis.
AB  - BACKGROUND: The role of adjuvant radiotherapy in stage I endometrial cancer has
      changed in recent years. This updated Cochrane systematic review aimed to
      reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in
      stage I endometrial cancer. METHODS: We searched various databases including The
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and
      the Specialised Register of the Cochrane Gynaecological Cancer Review Group
      (CGCRG) for randomized controlled trials that met the predefined inclusion
      criteria. The primary outcome was overall survival (OS); secondary outcomes were
      endometrial cancer-specific survival, locoregional recurrence, distant
      recurrence, and toxicity. Hazard ratios (HRs) were estimated and pooled if
      possible; otherwise, dichotomous data were extracted. All statistical tests were
      two-sided. RESULTS: Of the eight included trials, seven trials (3628 women)
      compared external beam radiotherapy (EBRT) and no EBRT (or vaginal brachytherapy
      [VBT]), and one trial (645 women) compared VBT and no additional treatment. EBRT
      statistically significantly reduced locoregional recurrence compared with no EBRT
      (or VBT alone) (HR = 0.36, 95% confidence Interval [CI] = 0.25 to 0.52; P <
      .001), but this did not translate into an improvement in OS (HR = 0.99, 95% CI =
      0.82 to 1.20; P = .95), endometrial cancer-specific survival (HR = 0.96, 95% CI =
      0.72 to 1.28; P = .80), or distant recurrence rates (risk ratio = 1.04, 95% CI =
      0.80 to 1.35; P = .77). EBRT was associated with an increased risk of severe
      acute toxicity, severe late toxicity, and reduced quality of life scores.
      CONCLUSIONS: EBRT reduces the risk of locoregional recurrence but has no
      statistically significant impact on cancer-related deaths or OS. However, EBRT is
      associated with clinically and statistically significant morbidity and a
      reduction in quality of life.

PMID- 22962694
TI  - Re: coffee consumption and prostate cancer risk and progression in the health
      professional follow-up study.

PMID- 22962695
TI  - Live/Real time three-dimensional transthoracic echocardiographic assessment of
      the involvement of cardiac valves and chambers in carcinoid disease.
AB  - We present an adult with metastatic carcinoid disease affecting the heart, in
      whom live/real time three-dimensional transthoracic echocardiography (3DTTE)
      provided incremental value over two-dimensional transthoracic echocardiography
      (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid
      regurgitation, but was unable to visualize the posterior leaflet of the tricuspid
      valve or the right (right anterior) leaflet of the pulmonic valve. Further
      analysis with 3DTTE demonstrated thickening, restricted mobility, and
      noncoaptation of all three leaflets of both the tricuspid and the pulmonary
      valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas
      permitted more reliable quantification of regurgitation severity. In addition,
      localized, linear, echogenic areas consistent with carcinoid deposits were noted
      along the inner walls of the right atrium, atrial septum, and inferior vena cava.
      To the best of our knowledge, endocardial carcinoid deposits have never been
      reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE
      enabled measurement of their dimensions and areas. Subcostal examination also
      identified large circumscribed hepatic lesions consistent with metastatic
      disease. Neither the carcinoid deposits nor the metastatic lesions were detected
      by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE
      in more comprehensively assessing carcinoid involvement of the heart.

PMID- 22962696
TI  - We must be open about our mistakes.

PMID- 22962697
TI  - Alzheimer's drugs take a new tack.

PMID- 22962698
TI  - India's forest area in doubt.

PMID- 22962699
TI  - Higher requirements of dialysis in severe lithium intoxication.
AB  - Severe lithium poisoning is a frequent condition in the intoxicated intensive
      care unit population. Dialysis is the treatment of choice, but no clinical
      markers predicting higher requirement for dialysis have been identified to date.
      We analyze the characteristics of lithium overdose patients needing dialysis to
      improve lithium clearance, and identify the ones associated with higher dialysis
      requirement. This is an observational, retrospective study of 14 patients with
      lithium poisoning admitted from 2004 to 2009. Median age was 41.8 +/- 16.1 years.
      Poisonings were acute in 7.1%, acute-on-chronic in 64.28%, and chronic in 28.5%
      of cases. Comparing clinical and biochemical data in patients requiring more than
      one dialysis session with those requiring only one session, the univariate
      analysis showed differences at admission in creatinine clearance (40.5 +/- 23 vs.
      73.3 +/- 24.9 mL/min, P = 0.025), white blood cells (17,528 +/- 3,530 vs. 11,580
      +/- 3360 cells/L, P = 0.007), and blood sodium concentration (134.8 +/- 5.9 vs.
      141.8 +/- 8.4 mmol/L, P=0.035). We measured the degree of association between the
      number of sessions and the variables with partial correlations. High lithium
      levels (P = 0.006, r = 0.69), low creatinine clearance (P = 0.04, r = -0.55), and
      low blood sodium concentration (P = 0.024, r = -0.59) were associated with a
      greater number of dialysis sessions. The correlation remained significant for
      blood sodium concentration (P = 0.016, r = -0.67) after adjustment for creatinine
      clearance and initial lithium levels. Presence on admission of low creatinine
      clearance, low blood sodium concentration, and/or high lithium levels correlated
      with a higher number of dialysis sessions in severe lithium poisoning. These
      factors, especially low blood sodium concentration, are associated with higher
      dialysis requirements in severe lithium intoxication.

PMID- 22962701
TI  - Electro-optic dye triggers ethics row.

PMID- 22962700
TI  - Trade deal to curb generic-drug use.

PMID- 22962702
TI  - Databases fight funding cuts.

PMID- 22962703
TI  - Voyager's long goodbye.

PMID- 22962704
TI  - China's dinosaur hunter: The ground breaker.

PMID- 22962705
TI  - Collaborations: A single cog in a complex machine.

PMID- 22962706
TI  - Climage change: Brief but warm Antarctic summer.

PMID- 22962707
TI  - ENCODE: The human encyclopaedia.

PMID- 22962708
TI  - Trouble for hospitals & health plans in states that nix Medicaid expansion.

PMID- 22962709
TI  - Computer-aided multispectral digital analysis (MelaFind) for assessing atypical
      skin lesions.

PMID- 22962710
TI  - AMA applauds claim processing improvement.

PMID- 22962712
TI  - Employers plan to push wellness programs more.

PMID- 22962711
TI  - Barriers to access attributed to formulary changes.

PMID- 22962713
TI  - The innovation challenge: Getting the message.

PMID- 22962714
TI  - July 2012: issue overview and highlights.

PMID- 22962715
TI  - Protecting the doctor-patient relationship.

PMID- 22962716
TI  - The importance of peer-review.

PMID- 22962717
TI  - Keep up the good work.

PMID- 22962718
TI  - The use of prophylactic vitamin K at birth.

PMID- 22962719
TI  - Collaborative care--more important than ever.

PMID- 22962720
TI  - Evaluation of GABA-chitosan nanoparticle induced cell signaling activation during
      liver regeneration after partial hepatectomy.
AB  - Liver damage due to infection, cirrhosis, accidents and diseases lead to
      destruction of hepatocytes and their regeneration to its original form is
      important for the proper functioning of the body. Gamma aminobutyric acid (GABA),
      a neurotransmitter, was coupled with a biopolymer chitosan and the nanosized
      complexes were made. The morphology was studied by scanning electron microscope
      and the interaction of GABA with chitosan was analysed by FT-IR spectroscopy. The
      interaction of GABA-chitosan nanoparticles with hepatocytes were observed by FITC
      labeled nanoparticles. After partial hepatectomy in male Wistar rats, DNA
      synthesis was estimated by tritiated thymidine uptake and the activity of
      thymidine kinase and protein synthesis by tritiated leucine uptake in
      hepatocytes. There was an increase in tritiated thymidine uptake in partially
      hepatectomised groups with nanoparticle treatment (GCNP) when compared to
      partially hepatectomised groups without nanoparticle treatment (PHNT) and with
      pure GABA treatment (G). Inositol 1,4,5 trisphosphate (IP3) content and gene
      expression of phospholipase C mRNA and nuclear factor kappa-light-chain-enhancer
      of activated B (NF-KB) mRNA was decreased for groups G and GCNP with respect to
      PHNT. Thus our results showed increased hepatocyte regeneration with decreased
      cell death in group G and more better with GCNP when compared to PHNT.

PMID- 22962721
TI  - Fabrication and characterization of hybrid nanofibers from poly(vinyl alcohol),
      milk protein and metal carbonates.
AB  - Porous three dimensional nanofibrous membranes were fabricated from poly(vinyl
      alcohol) (PVA), milk protein and inorganic salts such as calcium carbonate
      (CaCO3) or magnesium carbonate (MgCO3). Microscopic investigations showed that
      the fibers have smooth morphology with an average diameter of 300-500 nm and a
      surface area of 5.29 m2g(-1). Thermal analysis of the composite nanofibers showed
      a decrease in glass transition temperature as compared to PVA nanofiber.
      Incorporation of CaCO3 and MgCO3 into the nanofiber matrix was confirmed by
      energy dispersive spectroscopy and X-ray diffraction analysis. The
      cytocompatibility of electrospun composite nanofiber sheets was evaluated using
      human lung fibroblasts (IMR-90). There was an increase in cell attachment and
      cell density on milk protein incorporated to PVA-CaCO3 and PVA-MgCO3 fibers
      within a week of cell seeding. The cytocompatibility and increase in cell
      adhesion property of the hybrid nanofiber may provide significant advantages for
      such materials in biomedical applications.

PMID- 22962722
TI  - Ginsenosides extracted from nanoscale Chinese white ginseng enhances anticancer
      effect.
AB  - Ginsenosides, the major chemical composition of Chinese white ginseng (Panax
      ginseng C. A. Meyer), can inhibit tumor, enhance body immune function, prevent
      neurodegeneration. In this paper, for the first time we reported that the amount
      of ginsenosides in the equivalent extraction of the nanoscale Chinese white
      ginseng particles (NWGP) was 2.5 times more than that of microscale Chinese white
      ginseng particles (WGP). And the extractions from NWGP (1000 microg/ml) reached a
      high tumor inhibition of 64% exposed to human lung carcinoma cells (A549) and 74%
      exposed to human cervical cancer cells (Hela) after 72 h. Our work shows that the
      nanoscale Chinese WGP greatly improves the bioavailability of ginsenosides.

PMID- 22962723
TI  - Optimizing hemocompatibility of surfactant-coated silver nanoparticles in human
      erythrocytes.
AB  - Several recent biological science studies have been focused on nanotechnology and
      nanomaterials due to their potential use in biomedicine. Drug delivery systems
      are an example of biomedical applications utilizing nanoparticles. Silver
      nanoparticles (AgNPs) can be used for these drug delivery systems. However, the
      effects of cytotoxicity caused by AgNPs are not fully understood. Determining the
      optimal characteristics to facilitate the biocompatibility of AgNPs is an
      important subject for application. In the present study, human erythrocytes were
      used as an in vitro model to examine the size, dose, and coating surfactant
      dependent cytotoxicity of AgNPs. Our results demonstrated that
      polyvinylpyrrolidone (PVP) was a more suitable surfactant than polyethylene
      glycol (PEG) for AgNPs capping. In addition, we determined the appropriate
      particular size and dosage of AgNPs to reduce human erythrocytes hemolysis.
      Membrane damages including hemolysis, potassium efflux, protein leakage, and
      alterations in cell shape and membrane fragility were minimized with 100-nm AgNP
      particles. This study provides novel insights into AgNPs cytotoxicity and a basis
      for utilizing AgNPs for diagnostic and therapeutic applications.

PMID- 22962724
TI  - Formulation and pharmacokinetics evaluation of puerarin nanocrystals for
      intravenous delivery.
AB  - Puerarin is a very widely used drug for treating coronary heart disease. Owing to
      its poor water solubility and the adverse drug reactions caused by cosolvents
      having been confirmed by SFDA, the aim of present study was to construction and
      evaluation the puerarin nanocrystals in vitro and in vivo. The nanocrystals
      prepared were characterized using PCS, AFM, TEM, SEM and DSC. For the assessment
      of the pharmacokinetic parameters the developed formulations have been
      intravenous administered to beagle dogs. Results revealed that a narrow size
      distributed nanocrystals composed of crystallized spherical particles with a mean
      particle size of 423.6 +/- 17.3 nm, a poly-dispersity index of 0.13 +/- 0.07 and
      a negative charges around -30 mV was obtained. Puerarin dissolution velocity and
      saturation solubility were enhanced by the nanocrystals. DSC analysis revealed
      that the crystallinity of the puerarin was preserved during the high pressure
      homogenization and freeze-drying processes. Administration of the nanocrystals
      led to a mean plasma profile with almost similarly low variations in comparison
      to the reference solution, however with no initial blood peak as observed with
      the solution formulation. The puerarin nanocrystals exhibited a significantly (P
      < 0.05) reduced Cmax and clearance, and a significantly (P < 0.05) greater MRT,
      clearance and elimination half-life compared to the puerarin solution. These
      results revealed the opportunity to formulate puerarin in nanocrystals for
      intravenous delivery with higher safety.

PMID- 22962725
TI  - In vitro safety toxicology data for evaluation of gold nanoparticles-chronic
      cytotoxicity, genotoxicity and uptake.
AB  - Safety and toxic effects of nanoparticles are still largely unexplored due to the
      multiple aspects that influence their behaviour toward biological systems. Here,
      we focus the attention on 12 nm spherical gold nanoparticle coated or not with
      hyaluronic acid compared to its precursor counterpart salt. Results ranging from
      the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast
      cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells
      by endo-lysosomal pathway by an indirect measurement technique; and how gold
      nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably
      through an indirect mechanism due to oxidative stress. While coating them with
      hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell
      internalization. These results will be of great interest to medicine, since they
      indicate that gold nanoparticles (with or without coating) are suitable for
      therapeutic applications due to their tunable cell uptake and low toxicity.

PMID- 22962726
TI  - Effect of thickness on nanostructured SnO2 thin films by spray pyrolysis as
      highly sensitive H2S gas sensor.
AB  - Nanostructured SnO2 thin films were prepared by spray pyrolysis technique onto
      glass substrates with different thickness by varying quantity of precursor
      solution. The structural, optical and electrical properties of these films have
      been studied. The crystallographic structure of the films was studied by X-ray
      diffraction (XRD). It is found that the films are tetragonal with (110)
      orientation. The grain size increases with thickness. Atomic Force Microscopy
      (AFM) showed that the nanocrystalline nature of the films with porous nature. The
      grain size increased 14 to 29 nm with increase in film thickness. The studies on
      the optical properties show that the direct band gap value decreases from 3.75 to
      3.50 eV. The temperature dependence of the electrical conductivity was studied.
      The activation energies of the films are calculated from the conductance
      temperature characteristics. The nanostructured SnO2 thin films were used as
      sensing layers for resistive gas sensors. The dependence of gas sensing
      properties on the thickness of SnO2 thin films was investigated. The gas response
      of the SnO2 thin films towards the H2S gas was determined at an operating
      temperature of 150 degrees C. The sensitivity towards H2S gas is strongly
      depending on surface morphology of the SnO2 thin films.

PMID- 22962727
TI  - Characterization of surface accumulation and release of nanosilica during
      irradiation of polymer nanocomposites by ultraviolet light.
AB  - Polymer nanocomposites are increasingly used in applications that are subjected
      to harsh environments. Owing to polymer's susceptibility to photodegradation,
      nanofillers in a polymer nanocomposite may be released into the environments
      during the composite's life cycle. Such release potentially poses an
      environmental health and safety problem and may hinder commercialization of these
      advanced materials. This study investigated the fate and release of nanosilica
      from epoxy/nanosilica composites. Specially-designed holders containing
      nanocomposite specimens were irradiated with UV light in a well-controlled
      environmental chamber. UV irradiated samples were removed for measurements of
      polymer chemical degradation, mass loss, surface morphology, nanosilica
      accumulation on the composite surface, and nanosilica release. Epoxy matrix
      underwent rapid photodegradation, resulting in substantial accumulation of silica
      nanofillers on the composite surface and also release from the composite. A
      conceptual model for surface accumulation and release of nanosilica during UV
      irradiation of epoxy nanocomposites is presented.

PMID- 22962728
TI  - Voltage induced anomalous conductance switching behaviour in nematic liquid
      crystal-multiwalled carbon nanotube composite.
AB  - Investigations on the voltage induced conductance switching behavior in the
      nematic liquid crystal-multiwalled carbon nanotube composite have performed. We
      have found that, the system formed electrical conduction pathways with increasing
      voltages. Anomalous conductance switching took place at a certain threshold
      voltage. Percolation threshold voltage depends on the frequencies of the
      measuring electric field. We have made an analogy between concentration dependent
      percolation and voltage induced percolation. A two dimensional (2D)
      renormalization model calculation reveals that if the CNTs form a 2D network then
      percolation threshold concentration (p(c)) should be 0.768. After careful
      analysis we have found that voltage analogy of percolation threshold
      concentration in our system is also very close to the above value. The
      connectivity exponent (beta) for 2D site percolation agrees well with our
      proposed voltage induced percolation connectivity exponent. Which gives a glimpse
      that voltage induced percolating network may forms a two dimensional network in
      this particular system.

PMID- 22962729
TI  - Size- and temperature-dependent quantum confined dielectric effect in colloidal
      pbse and CdSe nanocrystals.
AB  - A new method is proposed to calculate the Stark shift induced by surface
      dielectric effect in colloidal nanocrystals. The effective mass approximation
      model is revised according to quantum confined dielectric effect. LUMO (the
      lowest unoccupied molecular orbital), HOMO (the highest occupied molecular
      orbital), band gap and Stark shift are calculated in CdSe and PbSe nanocrystals
      that bear significantly different physical properties. The calculated results fit
      well with the experimental data. The calculation of dielectric effect-induced
      Stark shift indicates that the quantum confined dielectric effect in PbSe and
      CdSe nanocrystals is size- and temperature-dependent, which is more notable in
      PbSe nanocrystals with a narrower band gap and results in the gentle variation of
      quantum confinement energy with particle size.

PMID- 22962730
TI  - Process optimization of preparation of ZnO-porous carbon composite from spent
      catalysts using one step activation.
AB  - The process parameters of one step preparation of ZnO/Activated Carbon (AC)
      composite materials, from vinyl acetate synthesis spent catalyst were optimized
      using response surface methodology (RSM) and the central composite rotatable
      design (CCD). Regeneration temperature, time and flow rate of CO2 were the
      process variables, while the iodine number and the yield were the response
      variables. All the three process variables were found to significantly influence
      the yield of the regenerated carbon, while only the regeneration temperature and
      CO2 flow rate were found to significantly affect the iodine number. The optimized
      process conditions that maximize the yield and iodine adsorption capacity were
      identified to be a regeneration temperature of 950 degrees C, time of 120 min and
      flow rate of CO2 of 600 ml/min, with the corresponding yield and iodine number to
      be in excess of 50% and 1100 mg/g. The BET surface area of the regenerated
      composite was estimated to be 1263 m2/g, with micropore to mesopore ratio of
      0.75. The pore volume was found to have increased 6 times as compared to the
      spent catalyst. The composite material (AC/ZnO) with high surface area and pore
      volume coupled with high yield augur economic feasibility of the process. EDS and
      XRD spectrum indicate presence of ZnO in the regenerated samples.

PMID- 22962731
TI  - Magnetic properties of textured CoPd nanocrystalline thin films.
AB  - CoPd is an important nanomaterial for magnetic and magneto-optic storage of
      information. In this work, CoPd alloyed thin films are grown via radio frequency
      magnetron sputtering on silicon, glass and polyimide substrates in a vacuum
      chamber with base pressure of 5 x 10(-8) mbar. The films are nanocrystalline with
      grain size between 4 and 80 nm. The magnetic properties of thoroughly textured
      CoPd alloyed thin films are compared to random polycrystalline ones.
      Magnetization hysteresis loops recorded under fields up to 12 kOe via a home-made
      magneto-optic Kerr-effect magnetometer reveal strong tendency for perpendicular
      magnetic anisotropy for the textured film. This anisotropy leads to the formation
      of well-defined stripe or labyrinthine ferromagnetic domains with the local spins
      oriented perpendicular to the film plane. The domain patterns and the hysteresis
      loops are simulated with micromagnetic calculations. Finally, an induced magnetic
      moment of 0.44 microB/atom is measured for Pd via X-ray magnetic circular
      dichroism and it is separated into spin and orbital magnetic moment
      contributions.

PMID- 22962732
TI  - Synthesis, growth mechanism and characterization of single crystalline alpha
      Fe2O3 spherical nanoparticles.
AB  - In the present report, we proposed a simple and efficient method for synthesizing
      single crystalline alpha-Fe2O3 spherical nanoparticles array into hexagonal
      dipyramid (HGDP) hierarchical structures using urea as a surface-active agent to
      control the growth and nucleation of the iron species. Growth mechanisms for the
      formation of HGDP hierarchical structures have been also proposed. Single
      crystalline feature, structural morphology and size of the nanoparticles were
      investigated by X-ray diffraction (XRD), Scanning and Transmission electron
      microscopy (SEM). The spectroscopic techniques such as; FT-IR, UV-VIS absorption
      and Raman spectroscopy were used to investigate optical response of the
      synthesized nanoparticles. Optical energy band gap was calculated to be 2.57 eV
      and 2.21 eV corresponding to direct and indirect transitions, respectively. The
      magnetic properties of the single crystalline nanoparticle were also investigated
      by Vibrating sample magnetometer (VSM) and found that they are weak ferromagnetic
      in nature. The values of saturation magnetization, remanent magnetization and
      coercivity were found to be 0.5925 emu/g and 0.1642 emu/g and approximately 1650
      Oe, respectively.

PMID- 22962733
TI  - Effect of point defects and impurities on the electronic transport of Au tipped
      ultranarrow PbS nanorods.
AB  - Electronic transport through single nanowire/nanorod directly probes the
      fundamental limits of semiconductor device miniaturization. Point defects or
      impurity centers form easily during the growth of nanorods/nanowires which may
      strongly affect the electronic transport efficiencies. Existing models of
      electronic transport are often unable to determine the role of defects and
      impurities at the nanoscale because there are significant differences between
      nanostructures and bulk materials arising from unique geometries and confinement.
      The effect of defect and impurities on the conductance of a model ultranarrow PbS
      rod was modeled using density functional theory. It was observed that the
      introduction of defects and Au impurities modified the orbital energies of PbS
      nanorods and reduced the conductance compared to the defect-free rod. The
      conductance for the nanorods with defects and impurities were limited by the
      number of available conduction channels required for efficient electronic
      conduction.

PMID- 22962734
TI  - Nanocomposite of Cu-TiO2-SiO2 with high photoactive performance for degradation
      of rhodamine B dye in aqueous wastewater.
AB  - The nanocomposite of Cu-TiO2-SiO2 photocatalyst have been prepared by a sol-gel
      method, which is used for the degradation of Rhodamine B (RB) as a probe that is
      notorious organic compound present in dyes wastewater. Morphological and
      structural characteristics of the Cu-TiO2-SiO2 nanocomposite were studied with
      low temperature N2 adsorption (BET), X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and UV-vis diffuse reflectance spectroscopy (DRS). The Fourier
      transformed infrared spectroscopy (FT-IR) analysis shows the enhanced chemical
      bonding of O-Ti and O-Ti-O after the composition of Cu and SiO2 species into
      TiO2. It is found that the Cu-TiO2-SiO2 nanocomposite exhibits much higher
      photocatalytic activity under both UV light and visible light irradiation as
      compared with that over commercial titania (Degussa P25) toward the dyes
      wastewater containing RB. The photodegradation rate of RB (5 mg/L) can reach
      above 95.0% under sunlight after 3 h. The addition of SiO2 not only inhibites the
      crystal growth and anatase-to-rutile transformation of TiO2 nanocatalyst, but
      also enhances the adsorption of organic compounds. Cu-doping extends the light
      response to the visible region. Synergetic effects between Cu-SiO2 and TiO2 have
      been investigated, which provides a good way and material in the degradation
      field of dyes wastewater.

PMID- 22962735
TI  - Improved performance of ZnO-based resistive memory by internal diffusion of Ag
      atoms.
AB  - An Ag/ZnO/Pt memory device, which has much better resistive switching behaviour
      than Pt/ZnO/Pt device was demonstrated. The detailed resistive mechanisms for the
      Pt/ZnO/Pt and the Ag/ZnO/Pt systems are proposed and investigated.
      Microstructures are observed by transmission electron microscope (TEM),
      indicating that the formation of conducting path for both systems is different.
      For the Pt/ZnO/Pt device, the conductive filament path is constructed by the
      oxygen vacancies from top to bottom electrodes under a larger enough bias at a
      forming process. For the Ag/ZnO/Pt device, the filament path was grown by oxygen
      vacancies combined with an internal diffusion of Ag atoms under a large bias and
      can provide the lowest energy barrier for electrons transported between two
      electrodes during set and reset processes, which reduces formation of other
      conducting paths after each switching. Accordingly, the stable switching
      performance of the Ag/ZnO/Pt device can be achieved over 100 cycles even the
      thickness of ZnO film <25 nm.

PMID- 22962736
TI  - Fast one-step method to synthesize TiO2 nanoparticle clusters for dye sensitized
      solar cells.
AB  - We have successfully designed a rapid method for producing dye sensitized solar
      cells (DSSC) using TiO2 films prepared by a modified dielectric barrier discharge
      jet (m-DBD jet) method which uses a DBD jet with elevated substrate temperatures
      from room temperature (RT) to 500 degrees C for approximately 10 min. This facile
      process has several advantages over other methods such as (1) eliminating
      additional coating and annealing steps, (2) creating films with high speed
      electron mobility via hierarchical pore clusters, and (3) allowing controlled
      TiO2 bandgap by N doping using atmospheric nitrogen instead of supplying N2 gas.
      Depending on reaction conditions, the resulting nanostructured materials have
      various sizes and shapes, with those deposited at the highest substrate
      temperatures displaying hierarchical walnut-shaped morphology as revealed by
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A
      possible growth mechanism of TiO2 nanoparticle clusters (TNC) is presented and
      discussed. Finally, this m-DBD jet method produces TNC films that exhibit
      approximately 4 times higher photo-conversion efficiency than the nanoparticle
      films by the unmodified DBD jet method.

PMID- 22962737
TI  - Vibration energy harvester with sustainable power based on a single-crystal
      piezoelectric cantilever array.
AB  - We designed and fabricated a bimorph cantilever array for sustainable power with
      an integrated Cu proof mass to obtain additional power and current. We fabricated
      a cantilever system using single-crystal piezoelectric material and compared the
      calculations for single and arrayed cantilevers to those obtained experimentally.
      The vibration energy harvester had resonant frequencies of 60.4 and 63.2 Hz for
      short and open circuits, respectively. The damping ratio and quality factor of
      the cantilever device were 0.012 and 41.66, respectively. The resonant frequency
      at maximum average power was 60.8 Hz. The current and highest average power of
      the harvester array were found to be 0.728 mA and 1.61 mW, respectively. The
      sustainable maximum power was obtained after slightly shifting the short-circuit
      frequency. In order to improve the current and power using an array of
      cantilevers, we also performed energy conversion experiments.

PMID- 22962738
TI  - FITC delivery into plant cells using magnetic single-walled carbon nanotubes.
AB  - In this paper, fluorescein isothiocyanate (FITC) was covalently bonded with
      magnetic single-walled carbon nanotubes (mSWCNTs) that were purified using our
      previous method. To demonstrate our design, mSWCNT-FITC was delivered into plant
      cells (canola and carrot cells) driven by external magnetic forces. From FACS
      results, the FITC delivery efficiency was about 100% for both two canola and
      carrot protoplasts, which were further confirmed by the confocal and sectional
      TEM images. Some mSWCNTs were found trapped both inside the endosomes of canola
      protoplast and outside endosome near the nuclear membrane of carrot protoplast
      according to the sectional TEM images. All results showed that mSWCNT is a good
      delivery carrier for biomolecules.

PMID- 22962739
TI  - Construction of hierarchical nanostructured TiO2/Bi2MoO6 heterojunction for
      improved visible light photocatalysis.
AB  - In this study, Bi2MoO6 hollow microspheres were modified by depositing TiO2
      nanoparticles through a simple hydrothermal method. The prepared TiO2/Bi2MoO6
      photocatalysts were characterized by scanning and transmission electron
      microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and UV-vis
      diffuse reflectance spectroscopy. The photocatalytic performance of the
      heterostructured catalysts was evaluated by degradation of methylene blue (MB)
      under visible-light irradiation (lambda>420 nm). The photocatalysts based on
      nanostructured Bi2MoO6 and TiO2 exhibit much higher photocatalytic activity than
      the single-phase Bi2MoO6 or TiO2 and the mechanical mixture of Bi2MoO6 and TiO2
      for degradation of MB under the same conditions. The results reported in this
      study provide insight into constructing other heterostructured photocatalysts.

PMID- 22962740
TI  - Temperature-controlled synthesis of CdSe nanocrystals with narrow size
      distribution.
AB  - CdSe quantum dots (QDs) with narrow size distribution and fine crystallinity were
      synthesized in paraffin liquid through temperature-control method. TEM, HRTEM,
      SEAD, XRD, PL and UV-VIS spectra were used to characterize the size, crystal
      structure and photoluminescence (PL) properties of CdSe nanocrystals. The PL
      spectra and TEM results revealed that the monodispersed and uniformed CdSe QDs
      with narrow size distribution were synthesized at a certain reaction temperature.
      HRTEM images combined with selected area electron diffraction (SAED) and XRD
      patterns illustrated that CdSe QDs showed near-perfect zinc-blende and wurtzite
      crystallinity at different temperatures. The Gibbs-Thomson calculation provided a
      thermodynamic explanation for obtaining the CdSe nanocrystals with narrow size
      distribution by temperature-control method.

PMID- 22962741
TI  - Shape effect on electronic and photovoltaic properties of CdS nanocrystals.
AB  - Changes in electronic and photovoltaic properties of semiconductor nanocrystals
      predominantly due to changes in shape are discussed here. Cadmium sulfide (CdS)
      semiconductor nanocrystals of various shapes (tetrapod, tetrahedron, sphere and
      rod) obtained using an optimized solvothermal process exhibited a mixed cubic
      (zinc blende) and hexagonal (wurtzite) crystal structure. The simultaneous
      presence of the two crystal phases in varying amounts is observed to play a
      pivotal role in determining both the electronic and photovoltaic properties of
      the CdS nanocrystals. Light to electrical energy conversion efficiencies
      (measured in two-electrode configuration laboratory solar cells) remarkably
      decreased by one order in magnitude from tetrapod --> tetrahedron --> sphere -->
      rod. The tetrapod-CdS nanocrystals, which displayed the highest light to
      electrical energy conversion efficiency, showed a favorable shift in position of
      the conduction band edge leading to highest rate of electron injection (from CdS
      nanocrystal to the wide band gap semiconductor viz. titanium dioxide, TiO2) and
      lowest rate of electron-hole recombination (higher free electron lifetimes).

PMID- 22962742
TI  - Large-area anodized alumina nanopore arrays assisted by soft ultraviolet
      nanoimprint prepatterning.
AB  - Aluminium anodization under optimized conditions can naturally generate close
      packed and aligned nanopore arrays, but the spatial extent of such regular pore
      arrangement is generally limited. Here we demonstrated the use of soft
      ultraviolet nanoimprint lithography to guide the formation of nanopores at
      specific locations, using an elastomer negative mold for the process. By
      anodizing at voltages which naturally led to the formation of pores with matching
      averaged interpore separation, pre-patterned triangular holes (diameter 100 nm,
      periodicity 350 nm) on aluminium thin films induced conformal growth of nanopores
      at pre-defined positions. In addition, pores in geometries other than close
      packed patterns were prepared, with square pore arrangement being demonstrated in
      this work. The influence of the anodization voltage on the final pore formation
      was also studied. Our results illustrated the possibility to fabricate well
      organized nanopore arrays with conditions far less stringent than those reported
      in literature, which has the potential to be adopted for applications where
      regular pore alignment are critical.

PMID- 22962743
TI  - Hydrangeas-like Bi2WO6: facile synthesis, visible-light driven photocatalysis and
      theoretical analysis.
AB  - Hydrangeas-like Bi2WO6 powders were synthesized successfully by salt-ultrasonic
      assisted hydrothermal process, which were characterized by scanning electron
      microscopy (SEM), Energy dispersive X-ray (EDS), X-ray diffraction (XRD), and UV
      visible diffuse reflectance spectra (UV-Vis DRS), respectively. Bi, W and O
      elements were contained in the product, which could be tested by EDS. The crystal
      structure of the catalyst was orthorhombic phase (JCPDS card no.73-1126). And the
      band gap was estimated to be 2.56 eV from the onset of UV-Vis absorption spectra
      of the catalyst. In addition, the photocatalytic activities of the products were
      investigated on the degradation of Rhodamine B (RhB). It demonstrated that
      photocatalysts exhibited excellent visible-light driven photocatalytic
      performance. And the target residue was less than 1% in 20 min under Xenon lamp
      irradiation. First-principles calculations based on density functional theory
      (DFT) were used to explore the electronic and optical properties of Bi2WO6. And
      the theoretical calculations could illustrate the photocatalytic performance of
      Bi2WO6 powders under visible light irradiation.

PMID- 22962744
TI  - Fabrication and characterization of highly crystalline and stable phase-pure
      rutile nanowires.
AB  - A homogeneous thin layer of TiO2 has been successfully coated on the surface of
      multiwalled carbon nanotubes (MWCNTs), which were produced by catalytic chemical
      vapor decomposition method, via an in situ sol-gel method. The obtained MWCNT
      TiO2 composite materials were heat treated in air at high temperatures,
      attempting to produce highly crystalline pure rutile nanowires. Through
      comprehensive characterization obtained by scanning electron microscopy (SEM),
      transmission electron microscope (TEM), energy dispersive X-ray (EDX), and X-ray
      powder diffraction (XRD), the effect of heat treatment on crystallization and
      phase transformation was discussed, and the effect of absence of MWCNTs on the
      morphology of pure rutile nanowires was analyzed. Both anatase and rutile phases
      exist after heat treatment in 700 degrees C while only rutile phase exists after
      heat treatment in 800 degrees C. The crystal size of rutile is formed to be
      significantly larger than that of anatase, and the hollow tubular structure is
      found to be destroyed which resulted in nanowire structure.

PMID- 22962745
TI  - Electrospun nanofibrous membranes for temperature regulation of microfluidic seed
      growth chips.
AB  - This paper reports a simple and effective approach to control statistical pore
      size distributions within electrospun nanofibrous membranes (ENMs), by choosing
      appropriate spinning times of electro-spinning deposition. Mean pore diameter of
      ENMs decreases exponentially with increasing spinning time. This pore-size
      control method is demonstrated to regulate amount of heat energy reaching
      microfluidic seed growth chips (SGC) and thus growth temperature of seeds on the
      chips, without using sophisticated semiconductor manufacturing techniques or
      additional on-chip electronic circuits. Decreasing mean pore diameter of ENMs
      causes to decrease the on-chip temperature, following a second-order polynomial
      trend. Phenotypic study based on real-time observation of root architecture is
      conducted on multiple SGCs under various temperature conditions obtained by using
      ENMs with different pore size distributions.

PMID- 22962746
TI  - Effect of surface nanomorphology and interfacial galvanic coupling of PEDOT
      titanium counter electrodes on the stability of dye-sensitized solar cell.
AB  - The present study demonstrates a novel approach by which titanium foils coated
      with electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) in combination
      with sputtered platinum can be processed into a high-surface area cathodes for
      dye-sensitized solar cells (DSSCs). A detailed study has been performed to
      elucidate how surface nanomorphology and I(-)/I(3-) redox reaction behaviors
      underlying these photocathodes impact the DSSC performances. From the analysis of
      the relevant electrochemical parameters, an intrinsic correlation between the
      photovoltaic performances and the cathode surface area has been deduced for such
      a system and explained on the basis of relative contributions of the galvanic
      coupling properties of the nanomorphology PEDOT film and platinum. Depending on
      the type of photocathodes incorporated, it was observed that these PEDOT coated
      cathodes can exhibit higher stability over a given time range and photo
      conversion efficiencies 12-40%, higher than that achievable in absence of the
      intermediate PEDOT coatings. It has been shown that DSSCs based on such metal
      polymer hybrid photo-cathodes allow significant room for improvement in the
      catalytic performance at the electrode/electrolyte interface.

PMID- 22962747
TI  - In vitro degradation behavior of silica nanoparticles under physiological
      conditions.
AB  - Understanding the degradability of silica nanoparticles is significant for the
      rational design of desired nanomaterials for various biomedical applications.
      However, the effect of the intrinsic properties of silica nanoparticles, such as
      particle shape, surface chemistry, and porosity, on kinetic degradation process
      under different extrinsic conditions has still received little attention. Herein,
      mesoporous silica nanoparticles (MSNs) with different aspect ratios (ARs, 1, 2,
      and 4), the corresponding PEG-functionalized MSNs, and amorphous Stober spherical
      silica nanoparticles were specially designed and their degradation was evaluated
      in in vitro simulated physiological media. The results show that shape, surface
      properties and porosity of nanoparticles, as well as the component of simulated
      physiological media, play important roles in tuning the degradation kinetics and
      behaviors. Sphere-shaped MSNs have a faster degradation rate than rod-shaped
      counterparts. Naked MSNs are eroded from particle external surface, while
      PEGylated MSNs from interior of particles. And spherical MSNs display more
      extensive degradation than amorphous silica nanoparticles. The presence of fetal
      bovine serum (FBS) in Dulbecco's Modified Eagle's Medium (DMEM) can accelerate
      the degradation process. These results can provide useful guidelines for the
      rational design of silica nanoparticles for biomedical applications.

PMID- 22962748
TI  - Structural and electrical properties of Gd3+ ion substituted CoGdxFe(2-x)O4 nano
      ferrites.
AB  - Nano particles of CoGdxFe(2-x)O4, with x = 0.0, 0.1, 0.3, 0.5 have been prepared
      by chemical co-precipitation method. The as synthesized particles are annealed at
      300 degrees C for two hours to improve crystallinity. The X-ray diffraction
      patterns reveal the single cobalt ferrite phase formation and the average
      crystallite size decreases to 7 nm in the Gd3+ ion doped sample (with x = 0.5)
      compared to 27 nm in case of un-doped cobalt ferrite sample. The electrical
      properties for the different compositions of Gd3+ ion substituted cobalt ferrite
      material were studied in the frequency range 100 Hz to 10 MHz at room temperature
      using WK impedance analyzer. It is found that the electrical conductivity of the
      samples increases with increasing Gd3+ ion concentration. The results of our
      investigations reveal a strong dependence of material properties on Gd3+ ion
      doping.

PMID- 22962749
TI  - Comparisons between TiO2- and SiO2-flux assisted TIG welding processes.
AB  - This study investigates the effects of flux compounds on the weld shape, ferrite
      content, and hardness profile in the tungsten inert gas (TIG) welding of 6 mm
      thick austenitic 316 L stainless steel plates, using TiO2 and SiO2 powders as the
      activated fluxes. The metallurgical characterizations of weld metal produced with
      the oxide powders were evaluated using ferritoscope, optical microscopy, and
      Vickers microhardness test. Under the same welding parameters, the penetration
      capability of TIG welding with TiO2 and SiO2 fluxes was approximately 240% and
      292%, respectively. A plasma column made with SiO2 flux exhibited greater
      constriction than that made with TiO2 flux. In addition, an anode root made with
      SiO2 flux exhibited more condensation than that made with TiO2 flux. Results
      indicate that energy density of SiO2-flux assisted TIG welding is higher than
      that of TiO2-flux assisted TIG welding.

PMID- 22962750
TI  - La(0.7)Sr(0.3)MnO3 nanoparticles based ultra-high sensitive ammonia chemical
      sensor.
AB  - A facile, reliable, reproducible and ultra-high sensitive aqueous ammonia
      chemical sensor has been fabricated based on the utilization of
      La(0.7)Sr(0.3)MnO3 nanoparticles (LSMO NPs), as efficient electron mediators, and
      reported in this paper. The LSMO NPs were prepared by hydrothermal protocol
      followed by the annealing process and characterized in detail in terms of their
      mophological, structural and compositional properties. The I-V technique based
      aqueous ammonia sensor exhibits an ultra-high sensitivity of 494.68 +/- 0.01
      microA cm(-2)mM(-1) and very low-detection limit of 0.2 microM with a response
      time less than 10 s. To the best of our knowledge, this is the first report in
      which LSMO is used as an efficient electron mediator for the fabrication of
      aqueous ammonia chemical sensor. Moreover, by comparing the literature, it is
      confirmed that the fabricated sensor exhibits highest sensitivity towards the
      detection of aqueous ammonia. This LSMO nanomaterial based research broadens the
      range of efficient electron mediators utilized for the fabrication of ultra-high
      sensitive chemical sensors.

PMID- 22962751
TI  - Titanate nanotubes as a promising absorbent for high effective radioactive
      uranium ions uptake.
AB  - In this study, titanate nanotubes with a layered structure were investigated for
      the uptake of radioactive uranium ions for the first time. The nanotubes have
      been successfully prepared with a reaction of Ti metal nanopowders and NaOH mixed
      solution by a novel and effective ultrasonic-assisted hydrothermal method. As the
      absorbent of radioactive ions, they have the ability to selectively adsorb
      radioactive U ions from water via ion exchange process and subsequently
      immobilize these ions in the nanotube sorbents without the need of further
      treatment after absorption. Sorption induces considerable deformation of the
      layer structures, resulting in the structures changing from the nanotubes to
      sheets and having the ability of permanent entrapment of the radioactive cations
      in these as-grown sheets. Our results have proved that titanate nanotubes can be
      used as a promising absorbent for the removal of nuclear leaking water at the
      first time.

PMID- 22962752
TI  - Mixing antisolvents induced modulation in the morphology of crystalline C60.
AB  - We present systematic studies of the synthesis of fullerene (C60) crystals with
      diverse morphologies by liquid-liquid interfacial precipitation (LLIP) method
      based on different alcohols as antisolvents and aromatic benzene as a solvent.
      C60 crystals are grown at liquid-liquid interface of mixed isopropyl alcohol
      (IPA) and tertiary butyl alcohol (TBA) with C60 solution in benzene. The role of
      mixing IPA and TBA on the morphology of C60 crystal is investigated. One
      dimensional (1 D) C60 nanowhiskers and polygon-shaped 2D sheets have been grown
      with individual IPA/benzene and TBA/benzene system, respectively. However, C60
      crystals of different morphology (1D, 2D or both), and the self-assembly of nano
      sized C60 into micron-sized crystals could be obtained upon mixing IPA and TBA
      and it is the mixing ratio which determines the morphology. Raman scattering and
      power X-ray diffraction measurements have shown that these materials are
      crystalline with cubic and hexagonal structures.

PMID- 22962753
TI  - Effect of pulsed electromagnetic field on growth and structure properties of ZnO
      nanorod arrays.
AB  - Well-aligned ZnO nanorod arrays had been prepared by hydrothermal methods
      assisted with pulsed electromagnetic field (PEMF). The effects of pulsed
      electromagnetic field on growth and structure properties of ZnO nanorod arrays
      were studied in detail. XRD and SEM analysis showed ZnO nanorod arrays had bigger
      length to diameter ratio and better verticality on the substrate. And the Raman
      analysis showed well-aligned ZnO nanorod arrays have highly crystallized wurtzite
      structure with much fewer defects after a pulsed electromagnetic field was
      introduced. At last, a possible mechanism of pulsed electromagnetic field acted
      on nanorod arrays was proposed.

PMID- 22962754
TI  - Synergistic effect of PVP and PEG on the behavior of silver nanoparticle-polymer
      composites.
AB  - Silver nanoparticles-polymer nanocomposites, Ag-(1 - x)PVP-(x)PEG, were
      synthesized by wet chemical method in the presence of polyvinylpyrrolidone (PVP)
      and polyethylene glycol (PEG). A mixture of two stabilizing agent PVP and PEG is
      found to play a crucial role in controlling the morphology of nanocrystalline
      silver particles in the composite. This is inferred based on the shape and size
      study of nanocrystalline silver using the X-ray diffraction, transmission
      electron microscopy, Uv-vis spectroscopy, FTIR, and surface enhance Raman
      studies. These results suggest asymmetrical growth of silver nanocrystalline
      particles in the presence of both PVP and PEG. Comparison of the thermal
      properties of the Ag-polymer nanocomposites with pure polymers, PVP and PEG,
      showed that the thermal stability of the nanocomposite deteriorates by as much as
      75 degrees C in the presence of low PEG concentration (x < or = 0.6) and improves
      by around 45 degrees C at higher PEG concentration (x > 0.6). The study highlight
      the fact that the morphology of nanocrystalline silver can be altered just by
      varying the polymer weight ratios rather than any processing parameters, thus
      offering a novel, simple, and controlled synthesis engineering route to the
      formation of nanocrystalline silver in polymer matrix.

PMID- 22962755
TI  - Ga filled nanothermometers with high sensitivity and wide measuring range.
AB  - Ga-filled MgO and silica nanotubes were fabricated by a simple one-step method.
      The height of the gallium column in both two kinds of nanotube varies linearly
      and reproducibly to the temperature change when in situ heating and cooling in
      transmission electron microscope, make them ideal nanothermometers for use in a
      wide variety of microenvironments. The Ga-filled MgO nanothermometer has a rather
      high sensitivity of 6.02 nm/degrees C in the measuring range of 30-450 degrees C,
      which is one of the most sensitive nanothermometer. In comparison, the Ga-filled
      silica nanothermometer has a moderate sensitivity of 1.15 nm/degrees C in a wide
      temperature range of 30-900 degrees.

PMID- 22962756
TI  - Differences in electrophysical and gas sensing properties of flame spray
      synthesized Fe2O3(gamma-Fe2O3 and alpha-Fe2O3).
AB  - Nanoscaled Fe2O3 powders as candidates for gas sensing material for hydrogen
      detection were synthesized by the high temperature flame spray assisted
      combustion of ferrocene dissolved in benzene. X-ray diffraction (XRD) and
      selected area electron diffraction (SAED) show that the as prepared nanopowder
      consists of maghemite (gamma-Fe2O3) with low crystallinity. Thermal post
      treatment causes a phase transformation towards hematite (alpha-Fe2O3)
      accompanied by an increase in the crystallinity. Upon exposure to air and
      hydrogen at elevated temperatures, both phases show a significant variation of
      conductivity and activation energy-as evidenced by impedance spectra-and thus a
      favorable sensor response, surpassing even that of flame-synthesized
      nanocrystalline tin dioxide. The conductivity has been identified as of
      electronic origin, affected by trap states located in the region adjacent to
      grain boundaries. Quantitative analysis of the impedance spectra with equivalent
      circuits shows that the conductivity is thermally activated and affected by the
      interaction of hydrogen with the sensor material. The calculated Debye screening
      length of gamma-Fe2O3 and alpha-Fe2O3 is about 27 nm and 16 nm, respectively,
      what contributes significantly to the sensitivity of the material. Gamma-Fe2O3
      and alpha-Fe2O3 exhibit high sensor response towards hydrogen in a wide
      concentration range. Gamma-Fe2O3 shows n-type semiconducting behavior up to 573
      K. Alpha-Fe2O3 shows p-type semiconducting behavior, as reflected in the dynamic
      changes of the resistivity. For both sensor materials, 523 K was the optimal
      operating temperature.

PMID- 22962757
TI  - Fabrication and high visible light photocatalytic properties of Cu/Cu2O
      nanocomposites by the one-pot solution-phase hydrothermal method.
AB  - Cu/Cu2O nanocomposites were synthesized by the one-pot solution-phase
      hydrothermal method. The resulting products were characterized by X-ray
      diffraction, field emission scanning electron microscope and X-ray photoelectron
      spectroscopy. Experimental results indicate that the content of Cu in the Cu/Cu2O
      CNs increasing with prolonged reaction time. The content of Cu in the Cu/Cu2O CNs
      plays an important role in the photocatalytic activity. The coexistence of Cu2O
      and Cu nanoparticles was propitious to the high photocatalytic activity owing to
      their hetero-junction effect. Compared with the Cu/Cu2O CNs with high Cu content
      (68-96 wt%) and pure Cu2O, the Cu/Cu2O CNs with low Cu content (2.1-9.2 wt%)
      exhibited improved photocatalytic activity on the degradation of MO solution
      under visible light irradiation, at the first 20 min of irradiation, the
      photodegradation efficiency of MO solution reach up to 99%, it is still as high
      as 95% even at the end of the fourth cycle. Little change is found in their phase
      compositions during the photocatalytic reaction process, except partial oxidation
      of particles surface. The HmechanismH for visible light driven photocatalytic
      activity enhancement over Cu/Cu2O CNs is discussed.

PMID- 22962758
TI  - A study of silver species on silver-exchanged ETS-10 and mordenite by XRD, SEM
      and solid-state 109Ag, 29Si and 27AI NMR spectroscopy.
AB  - Silver zeolites, especially Ag-ETS-10 and Ag-mordenite, actively bind xenon and
      iodine, two prime contaminants common to nuclear accidents. The evolution of
      silver species on silver exchanged ETS-10 (Ag/ETS-10) and mordenite (Ag/Mor) has
      been investigated by exposing the materials to a series of activation conditions
      in Ar, air and H2. The samples were characterized by XRD, SEM and solid-state
      109Ag, 29Si and 27AI MAS NMR. The silver reduction and structural evolution have
      been illustrated by those techniques. The effectiveness of one sample of each
      type of sieve was tested for its ability to trap mercury from a gas stream.
      However, the results from this study demonstrate that the adsorption
      characteristics of silver-loaded sieves cannot necessarily be predicted using a
      full complement of structural characterization techniques, which highlights the
      importance of understanding the formation and nature of silver species on
      molecular sieves.

PMID- 22962759
TI  - Sub-60 nm periodic grating feature patterning by immersion based 364 nm laser
      interference.
AB  - In this paper, we report a methodology to fabricate high resolution periodic
      grating features using high index prism based interferometer and i-line laser
      source. Features with sub-60 nm half pitch size were fabricated on i-line resist
      in an immersion medium using a prism of high index 1.939.

PMID- 22962760
TI  - Synthesis of Fe3O4 nanoparticles with tunable and uniform size through simple
      thermal decomposition.
AB  - A novel and facile method with low cost has been developed to fabricate Fe3O4
      nanoparticles (NPs) with tunable and uniform sizes by the thermal decomposition
      of iron oleate complex. The synthesis of iron oleate complex was carried out
      using a reaction between oleic acid and FeCl3 x 6H2O at low temperature. The
      decomposition of iron oleate complex occurs when the complex added in the
      solution of octadecene (ODE) and trioctylamine (TOA) with simple heat treatment.
      The X-ray diffraction pattern of a resulting sample indicated that Fe3O4 NPs
      formed during the decomposition of iron oleate complex. Preparation conditions
      including reaction time and temperature, the concentration of the complex, and
      the ratio of TOA and ODE strikingly affected the size and size distribution of
      resulting Fe3O4 NPs. Under optimal preparation conditions, the size of Fe3O4 NPs
      was adjusted (less than 20 nm in average diameter). The analysis of samples by a
      Fourier transform infrared spectroscopy confirmed the formation of iron oleate
      complex. Because the Fe3O4 NPs revealed a superparamagnetic property as well as
      tunable and uniform sizes, the NPs will be utilizable for further applications.
      This simple strategy with low cost has to give a useful enlightenment for the
      design and fabrication of magnetic oxide.

PMID- 22962761
TI  - Metal catalyst adsorption effects in the growth of carbon nanostructures on
      mesoporous material.
AB  - Mesoporous silica films were used as host for metal-based (Me = Fe, Co, Ni)
      nanoparticles via wet impregnation at pH = 5. A hydrogen ion beam was used to
      reduce the metallic oxide and hydroxides, previously detected by X-ray
      photoelectron spectroscopy, in metals. Chemical vapor deposition processes at
      three different conditions varying the acetylene-nitrogen proportion were
      performed on the mesoporous films decorated by different metal-based
      nanoparticles. The grown carbon nanostructures were characterized by high
      resolution transmission electron microscopy and scanning electron microscopy. The
      ability to grow carbon nanostructures decreases in the following order: Fe > Co >
      Ni. When pure acetylene is used, iron allows to form graphene sheets around the
      metal catalyst like carbon nanocapsules, whereas cobalt allows to form structures
      that seem to be carbon nanotubes. Nitrogen leads to control the size and shape of
      carbon nanocapsules for iron catalyst and avoid the growth of such carbon
      nanotube-like structures for cobalt catalyst.

PMID- 22962762
TI  - Structural and optical properties of glancing angle deposited TiO2 nanowires
      array.
AB  - TiO2 nanowires (NWs) have been synthesized by glancing angle deposition technique
      using e-beam evaporator. The average length 490 nm and diameter 80 nm of NWs were
      examined by field emission-scanning electron microscopy. Transmission electron
      microscopy emphasized that the NWs were widely dispersed at the top. X-ray
      diffraction has been carried out on the TiO2 thin film (TF) and NW array. A small
      blue shift of 0.03 eV was observed in Photoluminescence (PL) main band emission
      for TiO2 NW as compared to TiO2 TF. The high temperature annealing at 980 degrees
      C partially removed the oxygen vacancy from the sample, which was investigated by
      PL and optical absorption measurements.

PMID- 22962763
TI  - Application of field emission as backlight unit for liquid crystal displays.
AB  - The paper first analyzes the effect of backlight unit for liquid crystal displays
      on the respect of image quality and power consumption. A spatially and temporally
      addressable backlight is required in the future liquid crystal displays which
      have lower power consumption and higher image quality. Compared to the currently
      used light emitting diode backlight, the simulation results indicate that a
      rectangular-shaped backlight has better performances on the respect of reducing
      power consumption and improving image quality. A backlight cell based on the
      field emission is manufactured and studied. It uses a mixture of multi-wall
      carbon nanotubes and tetrapod-like zinc oxide nanostructures as the cathode and
      applies spin-coating process for fabrication. The experiment shows that such
      field emission backlight unit has a low turn-on field which enables a high
      backlight luminance at acceptable driving voltage. Besides, this mixture cathode
      helps to improve the uniformity of field emission in both spatial and temporal
      domain which is important for the application of backlight unit.

PMID- 22962764
TI  - Enhanced field-emission from a mixture of carbon nanotubes, ZnO tetrapods and
      conductive particles.
AB  - We report the enhancement of field-emission current from a mixture of carbon
      nanotubes, ZnO tetrapod-like nano structures, and conductive particles. Carbon
      nanotubes are deposited on the electrode as the field emitters. A MgO layer is
      printed around the cathode electrode, and ZnO tetrapod-like nano structures are
      deposited on this layer for the generation of secondary emission electrons. A few
      conductive particles are also distributed on the MgO layer by spraying or screen
      printing. These conductive particles enhance the transverse electric field around
      the cathode electrode. Consequently, more primary electrons emitted from the
      carbon nanotubes bombard on the ZnO tetrapods, and secondary emission electrons
      and scattered electrons are yielded. Finally, the field-emission current is
      enhanced obviously. As experimental results shown, a high field-emission current
      about 32 mA in a direct current emission mode has been obtained from a 0.5 cm2
      emission site when an electric field of 9 V/microm is applied between cathode and
      anode. Compared with a conventional carbon nanotube cathode, the field-emission
      current has been improved about 80%.

PMID- 22962765
TI  - Direct synthesis of hydrophobic graphene-based nanosheets via chemical
      modification of exfoliated graphene oxide.
AB  - Hydrophobic graphene-based material at the nanoscale was prepared by treatment of
      exfoliated graphene oxide with organic isocyanates. The lipophilic modified
      graphene oxide (LMGO) can then be exfoliated into the functionalized graphene
      nanoplatelets that can form a stable dispersion in polar aprotic solvents. AFM
      image shows the thickness of LMGO is approximately 1 nm. Characterization of LMGO
      by elemental analysis suggested that the chemical treatment results in the
      functionalization of the carboxyl and hydroxyl groups in GO via formation of
      amides and carbamate esters, respectively. The degree of GO functionalization can
      be controlled via either the reactivity of the isocyanate or the reaction time.
      Then we investigated the thermal properties of the SPFGraphene by using
      thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), the
      TGA curve shows a greater weight loss of approximately 20% occurred indicating
      removal of functional groups from the LMGO sheets and an obvious exothermic peak
      at 176 degrees can be observed from 150 to 250 degrees. We also compared the
      structure of graphene oxide with the structure of chemical treated graphene oxide
      by FT-IR spectroscopy. The morphology and microstructure of the LMGO nanosheets
      were also characterized by SEM and XRD. Graphene can be used to fabricate a wide
      range of simple electronic devices such as field-effect transistors, resonators,
      quantum dots and some other extensive industrial manufacture such as super
      capacitor, li ion battery, solar cells and even transparent electrodes in device
      applications.

PMID- 22962766
TI  - Spin transport in be edge-doped graphene nanoribbon.
AB  - We report an atomistic simulation of spin dependent charge transport in zigzag
      graphene nanoribbons with 4 zigzag chains doped by a Beryllium atom on one edge.
      The spin dependent density functional theory with norm-conserving atomic basis
      set is employed to describe the system and the current versus voltage behavior is
      calculated by the nonequilibrium Green's function method for quantum transport.
      The Be impurity atom suppresses the local magnetization near the edge and the
      transmitted charge current becomes spin polarized accordingly. Both spin-up and
      spin-down transmission spectra are modified significantly but in different ways.
      Distinguished from the previous doping results of other impurity elements, here
      we observe negative differential resistance for only one of the spins in the
      nonlinear transport regime below bias 1.5 V. Molecular projected Hamiltonian
      energy spectrum near the impurity shows that the impurity removes the energy
      degeneracy of spin in perfect ribbon. The current versus voltage shows
      semiconductor behavior with fluctuating spin polarization of amplitude up to 37%.

PMID- 22962767
TI  - Effect of CO on the field emission properties of tetrapod zinc oxide cathode.
AB  - Tetrapod zinc oxide (T-ZnO), being a kind of nano-material, has large specific
      surface area and surface binding energy, which will make it sensitive to the
      ambient gas condition. So the field emission properties will be influenced by the
      gas adsorption when being applied as the cathode materials of field emission
      devices. Carbon monoxide is the main residual gas in T-ZnO field emission
      devices. In this paper, carbon monoxide was introduced into a field emission
      device with T-ZnO emitters. The field emission currents of tetrapod ZnO were
      compared before and after exposure to CO.

PMID- 22962768
TI  - Enhanced electron transfer rate for quantum dot sensitized solar cell based on
      CNT-TiO2 film.
AB  - In this paper, we have fabricated a quantum dot sensitized solar cell (QDSSC)
      based on carbon nanotube (CNT) doped TiO2 mesopores film. As revealed by field
      emission scanning electron microscopy and absorption spectra, the CdSe QDs were
      adsorbed onto CNT-TiO2 nanocomposite. An improved efficiency is achieved for the
      CNT-TiO2/CdSe devices compared to that of TiO2/CdSe, which is due to the
      increased surface area and reduced charge recombination in TiO2 film by the
      presence of CNTs. A power conversion efficiency of the as-prepared QDSSC of 0.98%
      was obtained under 100 mW/cm2 solar irradiation. The emission decay profile
      demonstrates that the electrons transfer from CdSe QDs to CNT-TiO2 is faster than
      that from CdSe QDs to TiO2, resulting in the reduction of the charge
      recombination, leading to a higher FF value in QDSSC. The average lifetime of
      CdSe QDs adsorbed on TiO2 doped with CNT is 6.2 ns and the electron transfer rate
      constant of 1.1 x 10(8) s(-1) can be calculated.

PMID- 22962769
TI  - Pulsed laser assisted reduction of graphene oxide as a flexible transparent
      conducting material.
AB  - In this paper, we use a simple and highly-effective pulsed laser reducing method
      to fabricate flexible, transparent and conducting graphene film. The pulsed laser
      reducing process was monitored by digital camera and UV-visible spectroscopy. The
      obtained reduced graphene oxide (r-GO) was characterized by Raman spectroscopy.
      Based on this reducing method, the resulting r-GO films possessed a transmittance
      varied from 29% to 74% and a sheet resistance varied from 2.1 MOmega/[square] to
      840 Omega/[square], which was very close to chemically r-GO film.

PMID- 22962770
TI  - Vortex domain wall formation in permalloy nanowires with geometric pinning sites.
AB  - An optimal geometric pinning site on Permalloy nanowires of varying widths has
      been investigated and applied in a magnetic memory scenario using micromagnetic
      simulations. Minimal limits on two key factors; the applied field length and the
      domain wall formation length are established such that vortex domain walls are
      reliably formed in the structures to facilitate lower powered domain wall
      movement using spin-polarised current. The symmetric wires with the
      nanoconstrictions at both sides have been found to favour the formation of the
      vortex domain wall compared with the asymmetric wires with the nanoconstrictions
      at only one side of the wires. The detailed micromagnetic simulations show that
      the domain wall formation length and the applied field length are optimal to form
      the vortex domain walls when they are equal to the nanowire width.

PMID- 22962771
TI  - Ab initio study of structure and magnetism of late transition metal oxide TMnOm
      clusters (TM = Fe, Co, Ni, n = 1, 2, m = 1-6).
AB  - We systematically investigate the structural and magnetic properties of late
      transition metal oxide clusters, TMnOm (TM = Fe, Co, Ni; n = 1, 2; m = 1-6) by
      using ab initio density functional theory approach. FenOm clusters prefer to
      adopt three dimensional configurations, while ConOm and NinOm clusters are apt to
      form planar structures. The O atoms are all atomic bonding to Fe atoms in the
      FenOm clusters, and are partly molecularly adsorbed to Co(Ni) in ConOm(NinOm)
      clusters, such as Co2O(5-6) (NiO3, and Ni2O(4-6)). The average binding energies
      per atom of TMnOm show a monotonous increase trend with the increase of O atoms
      for both n = 1 and 2 for TM = Fe, Co and Ni, and reach the peak at m = 4 for
      TM2Om and decrease a little bit afterwards. The odd-even magnetic oscillation is
      major trait with the peaks at odd and bottoms at even sizes for Fe2Om and Ni2Om
      (m = 2-6), respectively and large magnetic moments are found in Co2O3 and Co2O6.

PMID- 22962772
TI  - Scaling the dynamic electron scattering in imaging the graphene sheets by the
      high-angle annular dark-field microscopy.
AB  - Employing the graphene sheets (GSs), the electron scattering constants are
      measured in the high-angle annular dark-field (HAADF) imaging by the scanning
      transmission electron microscopy. Single scattering is found to be dominant until
      the layer number of 200, complying with a simple relation of I = Io(1 - e(
      tau/lambda)). The discrete layer counting of the GSs enables precise
      determination of incident depths. This work results values of lambda = 48.2,
      61.4, 97.9 and 115.6 nm for 80, 120, 160 and 200 keV electrons, respectively. The
      uncertainties with the mean free paths and the cross sections are confined to 10
      percent. The dependences on the electron beam energy and the collection angle are
      discussed based on a multislice simulation.

PMID- 22962773
TI  - Recent progress on RE2O3-Mo/W emission materials.
AB  - RE2O3-Mo/W cathodes were prepared by powder metallurgy method. La2O3-Y2O3-Mo
      cermet cathodes prepared by traditional sintering method and spark plasma
      sintering (SPS) exhibit different secondary emission properties. The La2O3-Y2O3
      Mo cermet cathode prepared by SPS method has smaller grain size and exhibits
      better secondary emission performance. Monte carlo calculation results indicate
      that the secondary electron emission way of the cathode correlates with the grain
      size. Decreasing the grain size can decrease the positive charging effect of
      RE2O3 and thus is favorable for the escaping of secondary electrons to vacuum.
      The Scandia doped tungsten matrix dispenser cathode with a sub-micrometer
      microstructure of matrix with uniformly distributed nanometer-particles of
      Scandia has good thermionic emission property. Over 100 A/cm2 full space charge
      limited current density can be obtained at 950Cb. The cathode surface is covered
      by a Ba-Sc-O active surface layer with nano-particles distributing mainly on
      growth steps of W grains, leads to the conspicuous emission property of the
      cathode.

PMID- 22962774
TI  - ZnO nanomaterials based surface acoustic wave ethanol gas sensor.
AB  - ZnO nanomaterials based surface acoustic wave (SAW) gas sensor has been
      investigated in ethanol environment at room temperature. The ZnO nanomaterials
      have been prepared through thermal evaporation of high-purity zinc powder. The as
      prepared ZnO nanomaterials have been characterized with scanning electron
      microscopy (SEM), transmission electron microscopy (TEM) and X-ray Diffraction
      (XRD) techniques. The results indicate that the obtained ZnO nanomaterials,
      including many types of nanostructures such as nanobelts, nanorods, nanowires as
      well as nanosheets, are wurtzite with hexagonal structure and well-crystallized.
      The SAW sensor coated with the nanostructured ZnO materials has been tested in
      ethanol gas of various concentrations at room temperature. A network analyzer is
      used to monitor the change of the insertion loss of the SAW sensor when exposed
      to ethanol gas. The insertion loss of the SAW sensor varies significantly with
      the change of ethanol concentration. The experimental results manifest that the
      ZnO nanomaterials based SAW ethanol gas sensor exhibits excellent sensitivity and
      good short-term reproducibility at room temperature.

PMID- 22962775
TI  - Enhanced electron field emission from carbon nanotubes irradiated by energetic C
      ions.
AB  - The field emission performance and structure of the vertically aligned multi
      walled carbon nanotube arrays irradiated by energetic C ion with average energy
      of 40 keV have been investigated. During energetic C ion irradiation, the curves
      of emission current density versus the applied field of samples shift firstly to
      low applied fields when the irradiation doses are less than 9.6 x 10(16) cm(-2),
      and further increase of dose makes the curves reversing to a high applied field,
      which shows that high dose irradiation in carbon nanotube arrays makes their
      field emission performance worse. After energetic ion irradiation with a dose of
      9.6 x 1016 cm(-2), the turn-on electric field and the threshold electric field of
      samples decreased from 0.80 and 1.13 V/microm to 0.67 and 0.98 V/microm
      respectively. Structural analysis of scanning electron microscopy, transmission
      electron microscopy and Raman spectroscopy indicates that the amorphous carbon
      nanowire/carbon nanotube hetero nano-structures have been fabricated in the C ion
      irradiated carbon nanotubes. The enhancement of electron field emission is due to
      the formation of amorphous carbon nanowires at the tip of carbon nanotube arrays,
      which is an electron emitting material with low work function.

PMID- 22962776
TI  - Few-layer graphene direct deposition on Ni and Cu foil by cold-wall chemical
      vapor deposition.
AB  - We report an alternative synthesis process, cold-wall thermal chemical vapor
      deposition (CVD), is replied to directly deposit single-layer and few-layer
      graphene films on Ar plasma treated Ni and Cu foils using CH4 as carbon source.
      Through optimizing the process parameters, large scale single-layer graphene
      grown on Ni foil is comparable to that grown on Cu foil. The graphene films were
      able to be transferred to other substrates such as SiO2/Si, flexible transparent
      PET and verified by optical microscopy, Raman microscopy and scanning electron
      microscopy. The sheet resistance and transmission of the transferred graphene
      films on PET substrate were also discussed.

PMID- 22962777
TI  - Artificial permeability and antibonding magnetic resonance in a copper-structured
      metamaterial with symmetry-broken ring-plate resonators.
AB  - We numerically investigate the antibonding magnetic resonance in a metamaterial
      composed of rings and plates, with a particular attention to the influence of
      broken structural symmetry on the Fano-type transmission spectrum as well as the
      resonant artificial permeability. From the simulation results, it is obvious that
      the antibonding magnetic resonance with strong magnetic-dipole coupling is
      responsible for the Fano-type profile, since an increase of the structural
      asymmetry extent to reduce the magnetic field confinement in one of the gaps will
      form, in contrary, a Lorentzian resonance dip. The dual excitation pathways,
      i.e., electric and magnetic resonances, at destructive interference are the
      underlying reason of the Fano-type transmission response. Additionally, the
      structural-asymmetry dependence of the artificial permeability shows that the
      broken symmetry can strongly modify the effective permeability due to the
      altering magnetic-dipole interactions. It is found that an anti-resonant curve of
      permeability versus frequency will be resulted in if significant symmetry-broken
      structure is introduced.

PMID- 22962778
TI  - Structural studies of aluminium nitride embedded in amorphous carbon.
AB  - Aluminum nitride containing diamond-like carbon was fabricated with pulsed laser
      deposition without post processing. The compositions of the targets used were
      varied at 1, 5, 10, 15 at.% and pure carbon was used as a reference. The films
      were comprehensively characterized with Atomic force microscope (AFM), X-ray
      photoelectron spectroscopy (XPS) and Transmission electron microscopy (TEM).
      Roughness analysis using AFM showed an increasing root-mean-square (RMS)
      roughness with increasing AIN content in target, while XPS analysis showed that
      the aluminum-nitrogen bonding was still present in the films after the
      fabrication process. Microstructural studies and selected area electron
      diffraction (SAED) pattern confirmed the presence of AIN crystals in DLC matrix.
      This nanostructured composite material is useful for luminescence applications.

PMID- 22962779
TI  - Field emission properties of AIN nanostructures.
AB  - AIN with different morphologies, including thin film, nanowires, nanoneedles and
      nanochilies, depending on the controlled growth parameters, have been
      successfully synthesized by chemical vapor deposition technique. Field emission
      properties have been systematically studied. The experimental results show that
      all AIN nanostructures have good field emission properties. In comparison, AIN
      nano-chilies possess the best field emission properties with a low turn-on and
      threshold fields of 1.8 V/microm and 3.1 V/microm, respectively. The results
      suggest that the morphological modulation is an effective way to optimize field
      emission performance of nanostructures.

PMID- 22962780
TI  - The effect of different temperature profiles upon the length and crystallinity of
      vertically-aligned multi-walled carbon nanotubes.
AB  - We synthesized vertically-aligned multi-walled carbon nanotubes with an inner
      diameter of 1.6-7.5 nm and stack height of 80-28600 microm by chemical vapor
      deposition. The effects of synthesis conditions such as substrate position in the
      tube furnace, maximum temperature, temperature increasing rate and synthesis
      duration on the structure of nanotubes were investigated. It was found that
      slightly faster temperature increase rate resulted in significantly longer
      length, larger diameter and more defects of nanotubes. Structural parameters such
      as inner, outer diameters, wall thickness and defects were investigated using
      transmission electron microscopy and Raman spectroscopy.

PMID- 22962781
TI  - Monolayer polystyrene micro-spheres array master derived by spin-coating method
      for UV nanoimprint.
AB  - Polystyrene micro-spheres aqueous suspensions were obtained by an emulsifier-free
      polymerization method. Fourier transform infrared spectroscopy and laser particle
      size distribution were used to characterize the colloidal solutions. Results
      indicate that the polystyrene micro-spheres colloidal solution has a good
      dispersion and the micro-spheres have a uniform size and smooth surface. The as
      prepared polystyrene micro-spheres colloidal solution was spun onto glass
      substrates and then the coated sample was heated at 70 degrees C for 1 h to form
      close-packed monolayer polystyrene microspheres arrays, which are used as a
      master. Scanning electron microscopy was used to observe the morphological
      properties of the polystyrene micro-spheres array. A relative good result can be
      easily obtained by a spinning speed of 2000 rpm for 30 second, when the solution
      concentration is around 10 wt.%. Furthermore, the polydimethylsiloxane soft mold
      was replicated from the-fabricated polystyrene micro-spheres array master and was
      then imprinted onto the photosensitive hybrid film under UV-irradiation and thus
      the micro-lens arrays built in the photosensitive hybrid sol-gel film were
      obtained.

PMID- 22962782
TI  - Structures and field emission properties of silicon nanowire arrays implanted
      with energetic carbon ion beam.
AB  - Structures and field emission properties of silicon nanowire arrays (SiNWAs),
      which were fabricated by using of electroless-chemical etching method and post
      implanted by the energetic carbon ion beam with an average energy of 20 keV at
      various doses, have been investigated. Structural analysis of SEM and XPS shows
      that SiC compound had been formed at the top of SiNWAs, and Si-C/Si composite
      nanostructure had been obtained. Compared to as-grown SiNWAs, the C ion implanted
      SiNWAs have better field emission characteristics. The turn-on field and the
      applied field at 100 microA/cm2 are reduced from 5.01 V/microm and 5.93 V/microm
      for as-grown SiNWAs to 4.45 V/microm and 5.40 V/microm for SiNWAs implanted at
      the dose of 1 x 10(16) cm(-2), respectively. However, large implanting amounts
      made serious structural damages at the top of nanowires, and impaired the field
      emission characteristics. The influence of energetic C ion implantation on the
      structures and field emission properties of SiNWAs has been discussed.

PMID- 22962783
TI  - Effects of porous silicon morphology on ballistic electron emission.
AB  - Porous silicon ballistic electron emission source with a structure of
      metal/porous silicon/Si/metal is obtained by anodization, rapid thermal
      oxidation, and sputtering. The microstructures of porous silicon layers are
      characterized by means of scanning electron microscope. The results show that
      disordered pores are formed at anodization current densities of 15 mA/cm2, 30
      mA/cm2, and 45 mA/cm2 for 5 min, respectively. However, straight pores are formed
      at anodization current densities of 60 mA/cm2, and 75 mA/cm2 for 5 min,
      respectively. The electron emission characteristic of porous silicon ballistic
      electron emission sources is measured in vacuum. The results show that electrons
      emitted into the vacuum from the porous silicon samples with disordered pores.
      Under a bias condition, injected electrons from the substrate are accelerated by
      the strong electric field on the surfaces of the Si nanocrystallites in
      disordered pores, and then emitted into the vacuum through Pt film. However, no
      electron emission is observed in porous silicon samples with straight pores. It
      attributes to the lack of Si nanocrystallites in straight pores. So there is not
      accelerating tunnels enough for electrons. According to disordered or straight
      pores, we can estimate whether PS samples emit electrons or not.

PMID- 22962784
TI  - Hydrothermal synthesis of perovskite bismuth ferrite crystallites with the help
      of NH4Cl.
AB  - Bismuth ferrite nanopowders were hydrothermally synthesized with and without
      NH4Cl for comparison. The effects of NaOH concentration, reaction temperature and
      reaction time on the product phases and morphologies were studied in detail. Pure
      BiFeO3 was synthesized in a wide hydrothermal condition with the help of NH4Cl.
      Especially, it can be synthesized at low temperature of 140 degrees C. X-ray
      diffraction and Fourier transform infrared spectra revealed the BiFeO3 products
      had a perovskite structure. Scanning electron microscopy images showed that
      different BiFeO3 morphologies were formed under different hydrothermal
      conditions. NH4Cl played a key role in the BiFeO3 formation and BiFeO3
      morphologies. Part BiFeO3 samples exhibited weak magnetic properties.

PMID- 22962785
TI  - Study on the infrared property of polyaniline/multi-wall carbon nanotube
      composite.
AB  - Composites of polyaniline (PANI) and multi-wall carbon nanotube (MWNT) were
      synthesized by in situ polymerization with different MWNT content. The composites
      were characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning
      electron microscopy (SEM), and thermogravimetric analysis (TGA). The SEM photos
      indicated that a mass of MWNT was enchased into PANI matrix when the content of
      MWNT was low. With the MWNT content increases, the surface of MWNT was covered
      with PANI and formed the core-shell structure. From the FT-IR spectroscopy of the
      composites, it can be confirmed that there was interaction between PANI and multi
      wall carbon nanotube. The composites had better thermal stability than pure PANI.
      Infrared emission property of the composites was analyzed by an IR-II infrared
      emissivity instrument and an infrared camera. It was found that infrared emission
      of the composites was lower than pure PANI in all wavelength range and infrared
      emissivity value was related to the content of MWNT in the composites.

PMID- 22962786
TI  - Magnetic properties of (Fe50Co50)(1-x)-Gdx thin films with diluted Gd doping.
AB  - (Fe50Co50)(1-x)-Gdx thin films (30 nm) with x<15% deposited on silicon substrates
      by magnetron sputtering were investigated by X-ray diffraction, vibrating sample
      magnetometer, and ferromagnetic resonance. Theoretical fittings of the angular
      dependent ferromagnetic resonance field of the FeCoGd films have been performed
      using the Landau-Lifshitz equation It is found that the ferromagnetic resonance
      experimental data is well fitted by the theory and various magnetic properties
      have been extracted in accordance. The saturation magnetization decreases from
      22750 Oe at x = 0% to 14079 Oe at x = 14% in the FeCo-Gd film, and the
      perpendicular magnetic anisotropy has changed from an easy film plane to an easy
      film normal geometry. The gyromagnetic ratio, as well as the Lande g factor, are
      found increased also with increasing Gd content, i.e. from g = 2.08 at x = 0% to
      g = 2.29 at x = 14%. An enhancement of the L-S coupling in the presence of a low
      Gd content has been concluded based on an observable increase from 0.011 at x =
      12% up to 0.015 at x = 14% in the Gilbert damping.

PMID- 22962787
TI  - Annealing temperature and ultraviolet irradiation effect on the ferroelectric
      properties of Bi(3.25)La(0.75)Ti3O12 thin films.
AB  - Bi(3.25)La(0.75)Ti3O12 thin films were prepared on Pt/Ti/SiO2/Si substrates by
      the metal organic decomposition method. The structural characterizations and the
      surface morphology observations were carried out applying X-ray diffraction and
      atomic force microscope, respectively. The annealing temperature and the
      ultraviolet irradiation effect on the ferroelectric properties were studied. It
      was found that the remnant polarization (Pr) and the coercive field (Ec)
      increased with the increase of the applied electric field (E) for all films. With
      the annealing temperature increasing from 670 degrees C to 750 degrees C, the
      increase tendency of Pr(E) and Ec (E) got enhanced from 670 degrees C to 720
      degrees C, followed by weakened from 720 degrees C at 750 degrees C. These
      phenomena could be well explained by the different internal strain in films. The
      remnant polarization and the coercive field showed an obvious decrease when the
      top electrodes of the thin films were illuminated with UV light due to the
      screening effect of trapped charge carries.

PMID- 22962788
TI  - First-principles study of AuC60 clusters.
AB  - Au atom has five patterns to form exdohedral AuC60 complexes. In this study we
      performed extensive density functional theory calculations on the five isomers to
      compare their geometrical and electronic properties. The one-fold bonding is
      found energetically more favorable than the commonly studied five- or six-fold
      bonding at all levels of theory conducted in this study. Comparisons with anionic
      and cationic AuC60, HAuC60 and MC60 (M = Li, Na, K, Cu, Ag) systems are made to
      illustrate their stability-structure correlations. Similar interaction patterns
      are adopted by HAuC60 and charged AuC60, while different patterns are found for
      alkali metal C60 complexes.

PMID- 22962789
TI  - Work function measurement for Ag-TCNQ (TCNQ = tetracyanoquinodimethane)
      nanowires.
AB  - The Ag-TCNQ (TCNQ = tetracyanoquinodimethane) nanowires synthesized by a vapor
      transport reaction exhibit promising field emission properties. Their effective
      work function at high applied electric field was estimated to be about 1.70 eV
      according to the Fowler-Nordheim (F-N) theory. In this work, we directly measured
      the intrinsic work function of Ag-TCNQ nanowires via the ultraviolet
      photoemission spectroscopy (UPS). According to the threshold binding energy, the
      work function is obtained to be 5.45 eV, which shows a large discrepancy with the
      preivous estimation based on F-N theory. The reductive effecitive work function
      during the field emission is mainly attributed to the morphology-induced
      enhancement of the nanowire array.

PMID- 22962790
TI  - Field electron emission from hydrogen plasma treated nano-ZnO thin films.
AB  - A nano-Zno films are deposited on the Mo film/ceramic substrates by using the
      electron beam vapor deposition technique. Then a hydrogen plasma treated method
      is used to improve the characteristics of ZnO thin films by microwave plasma
      chemical vapor deposition system. Effects of process parameters on morphologies
      and structures of the ZnO thin films are detected and analysed by field emission
      scanning electron microscopy, X-ray diffraction spectrum and energy dispersive
      spectrum. The experimental result indicates that the hydrogen plasma treated
      techniques can essentially reduce the surface resistance and improve the field
      emission current density of the nano-ZnO thin films. For the hydrogen plasma
      treated sample, its field emission current density can increased more than three
      times at 2.2 V/microm electric field condition.

PMID- 22962791
TI  - Growth and characterization of bamboo-shaped carbon nanotubes using nanocluster
      assembled ZnO:Co thin films as catalyst.
AB  - Bamboo-shaped carbon nanotubes (CNTs) had been successfully fabricated by a
      plasma enhanced chemical vapor deposition method, in which nanocluster-assembled
      ZnO:Co thin film was used as catalyst. It was found that bamboo-shaped CNTs were
      generally grown in a direction perpendicularly to the substrate surface with the
      tops of CNTs dominated by the droplet-like catalyst covered by the carbon layer.
      The diameter of CNTs was ranged from 20-50 nm. High resolution of TEM image
      showed that the typical CNT had a multi-walled structure with an inner core
      presented. The ordered graphite layers were inclined to an axis of CNT about 18
      degrees and the interlayer space of a CNT was about 0.35 nm. Two peaks in Raman
      spectrum at 1586 cm(-1) and 1372 cm(-1) were identified as G-band and D-band for
      graphite, respectively. The results showed that catalyst based on ZnO:Co thin
      films could be used for the growth of CNTs with bamboo-shaped structure.

PMID- 22962792
TI  - The microstructure and electrochemical characteristics of LiFePO4/carbon-network
      composite.
AB  - LiFePO4/carbon-network composite was synthesized by a high temperature solid
      state method using the natural sawdust as carbon precursor. The microstructure of
      the as-synthesized sample was characterized using X-ray diffraction (XRD),
      transmission electron microscopy (TEM), high resolution transmission electron
      microscopy (HRTEM), respectively. The results revealed that the LiFePO4 particles
      with diameters ranging from 30 to 150 nm were well connected by carbon networks.
      The electrochemical performance of the composite was characterized using
      galvanostatic charge-discharge technique. The initial discharge capacity of
      LiFePO4/carbon-network cathode reached 126 mAh x g(-1) with 0.2 C rate.

PMID- 22962793
TI  - Controlled formation of Ni(DMG)2 microrods/tubes by manipulating the kinetics of
      chemical reactions and their application in naked-eye sensors.
AB  - We have demonstrated controlled preparation of Ni(DMG)2 microrods/tubes via
      chemical reaction method. By manipulating the reaction kinetics via the
      concentration of reactants, shapes of the resulting microstructures can be easily
      tuned from microrods to microtubes. Size of the resulting products can also be
      controlled through changing the reaction temperatures. It was proposed that under
      high reactants' concentrations, molecules will prefer to grow at corners or edges
      of nuclei with high free energies, to reduce the total energy in the system,
      which would lead to partial or complete hollow interiors and eventually resulted
      in mircotubes. The fact that DMG show high selectivity with Ni2+ and accompanied
      with obvious color change enable us to fabricate test strip for naked-eye
      detection of Ni2+. Benefit from the large surface areas of DMG nanoparticles on
      the test strip, the detection limit is improved by two orders over that of
      conventional solution method. This strategy is sensitive, simple and easy to
      handle, thus expected to possess potentials for the practical Ni2+ detection
      applications.

PMID- 22962794
TI  - Aggregate domain growth of gold nanoparticle on chemically modified glass
      surface.
AB  - The aggregation of Au nanoparticle (AuNP) on a glass surface functionalized with
      3-aminopropyltrimethoxysilane (APTMS) was studied by means of UV-vis spectroscopy
      and AFM measurements. The optical response of AuNP due to localized surface
      plasmon resonance (LSPR) was increased with the increment of AuNP amount on the
      functionalized glass surface, then the changes of spectral shape corresponds to
      the aggregate formation was finally observed. The AFM image shows in homogeneous
      aggregation of nanoparticles on the substrate surface. Three-dimensional
      aggregate growth was observed.

PMID- 22962795
TI  - Effect of ultraviolet illumination and ambient gases on the photoluminescence and
      electrical properties of nanoporous silicon layer for organic vapor sensor.
AB  - The purpose of this research, the nanoporous silicon layer were fabricated and
      investigated the physical properties such as photoluminescence and the electrical
      properties in order to develop organic vapor sensor by using nanoporous silicon.
      The Changes in the photoluminescence intensity of nanoporous silicon samples are
      studied during ultraviolet illumination in various ambient gases such as
      nitrogen, oxigen and vacuum. In this paper, the nanoporous silicon layer was used
      as organic vapor adsorption and sensing element. The advantage of this device are
      simple process compatible in silicon technology and usable in room temperature.
      The structure of this device consists of nanoporous silicon layer which is formed
      by anodization of silicon wafer in hydrofluoric acid solution and aluminum
      electrode which deposited on the top of nanoporous silicon layer by evaporator.
      The nanoporous silicon sensors were placed in a gas chamber with various organic
      vapor such as ethanol, methanol and isopropyl alcohol. From studying on
      electrical characteristics of this device, it is found that the nanoporous
      silicon layer can detect the different organic vapor. Therefore, the nanoporous
      silicon is important material for organic vapor sensor and it can develop to
      other applications about gas sensors in the future.

PMID- 22962796
TI  - Hydrogen storage studies of palladium decorated nitrogen doped graphene
      nanoplatelets.
AB  - Hydrogen storage in materials is of significant importance in the present
      scenario of depleting conventional energy sources. Porous solids such as
      activated carbon or nanostructured carbon materials have promising future as
      hydrogen storage media. The hydrogen storage capacity in nanostructured carbon
      materials can be further enhanced by atomic hydrogen spillover from a supported
      catalyst. In the present work, the hydrogen storage properties of nitrogen doped
      graphene nanoplatelets (N-GNP) and palladium decorated nitrogen doped graphene
      nanoplatelets (Pd/N-GNP) have been investigated. The results show that hydrogen
      uptake capacity of nitrogen doped graphene nanoplatelets and palladium decorated
      nitrogen doped graphene nanoplatelets at pressure 32 bar and temperature 25
      degrees C is 0.42 wt% and 1.25 wt% respectively. The dispersion of palladium
      nanoparticles increases the hydrogen storage capacity of nitrogen doped graphene
      nanoplatelets by 0.83 wt%. This may be due to high dispersion of palladium
      nanoparticles and strong adhesion between metal and graphene nanoplatelets over
      the surface of N-GNP, which enhances the spillover mechanism. Thus, an increase
      in the hydrogen spillover effect and the binding energy between metal
      nanoparticles and supporting material achieved by nitrogen doping has been
      observed to result in a higher hydrogen storage capacity of pristine GNP.

PMID- 22962797
TI  - Synthesis and thermal transport studies of nanofluids based on metal decorated
      photochemically oxidized multiwalled carbon nanotubes.
AB  - Nanoparticle fluid suspensions were prepared using photochemically functionalized
      multiwalled carbon nanotubes in polar base fluids. Multiwalled carbon nanotubes
      prepared by catalytic chemical vapour deposition technique have been
      functionalized by irradiating with ultraviolet light of wavelength 254 nm. The
      photochemical oxidation of multiwalled carbon nanotubes under UV irradiation
      introduces oxygen containing functional groups onto the surface of the nanotubes,
      generating new defects on their structure. Silver nanoparticles have been
      deposited over multiwalled carbon nanotubes by chemical method. The enhancement
      in thermal conductivity of the prepared nanofluids using functionalized
      multiwalled carbon nanotubes and Ag nanoparticles deposited functionalized
      multiwalled carbon nanotubes with volume fraction, temperature and aspect ratio
      has been demonstrated. Silver deposited functionalized multiwalled carbon
      nanotubes based nanofluids in DI water with 0.02% volume fraction exhibit a
      thermal conductivity enhancement of 9.9% and 47% at room temperature and at 50
      degrees C respectively.

PMID- 22962798
TI  - Nanotechnology in automotive industry: research strategy and trends for the
      future-small objects, big impacts.
AB  - The goal of this paper is to emphasize and present briefly the nanotechnology
      science and its potential impact on the automotive industry in order to improve
      the production of recent models with an optimization of the safety performance
      and a reduction in the environmental impacts. Nanomaterials can be applied in car
      bodies as light weight constructions without compromising the stiffness and
      crashwortiness, which means less material and less fuel consumption. This paper
      outlines the progress of nanotechnology applications into the safety features of
      more recent vehicle models and fuel efficiency, but also emphasis the importance
      of sustainable development on the application of these technologies and life
      cycle analysis of the considered materials, in order to meet the society trends
      and customers demands to improve ecology, safety and comfort.

PMID- 22962799
TI  - Fabrication of a glucose biosensor based on citric acid assisted cobalt ferrite
      magnetic nanoparticles.
AB  - A novel and practical glucose biosensor was fabricated with immobilization of
      Glucose oxidase (GOx) enzyme on the surface of citric acid (CA) assisted cobalt
      ferrite (CF) magnetic nanoparticles (MNPs). This innovative sensor was
      constructed with glassy carbon electrode which is represented as (GOx)/CA
      CF/(GCE). An explicit high negative zeta potential value (-22.4 mV at pH 7.0) was
      observed on the surface of CA-CF MNPs. Our sensor works on the principle of
      detection of H2O2 which is produced by the enzymatic oxidation of glucose to
      gluconic acid. This sensor has tremendous potential for application in glucose
      biosensing due to the higher sensitivity 2.5 microA/cm2-mM and substantial
      increment of the anodic peak current from 0.2 microA to 10.5 microA.

PMID- 22962800
TI  - Local nanoelectromechanical properties of multiferroics Gd-doped BiFeO3-BaTiO3
      solid solution.
AB  - Bi(1-x-y)GdxBayFe(1-y)TiyO3 (x = 0.1 and y = 0.1, 0.2, 0.3) solid solutions have
      been prepared via solid state reaction method with the aim to obtaining
      magnetoelectric coupling (i.e., linear relation between magnetization and
      electric field) at room temperature. Optimum calcination and sintering strategies
      for obtaining pure perovskite phase, high density ceramics and homogeneous
      microstructures have been determined. The maximum ferroelectric transition
      temperature (Tc) of this system was 150-170 degrees C with the dielectric
      constant peak of 2300 at 100 kHz for y = 0.1. Well saturated piezoelectric loops
      were observed for all composition indicating room temperature ferroelectricity.
      Hardness and Young's modulus decrease with depth and with increasing
      concentration y.

PMID- 22962801
TI  - Wet-chemical green synthesis of L-lysine amino acid stabilized biocompatible iron
      oxide magnetic nanoparticles.
AB  - In this paper, we report a novel method for the synthesis of L-Lysine (lys) amino
      acid coated maghemite (gamma-Fe2O3) magnetic nanoparticles (MNPs). The facile and
      cost effective method permitted preparation of the high-quality superparamagnetic
      gamma-Fe2O3 MNPs with hydrophilic and biocompatible nature. For this work, first
      we synthesized magnetite phase Fe3O4/lys by wet chemical method and oxidized to y
      Fe2O3 in controlled oxidizing environment, as evidenced by XRD and VSM
      magnetometry. The crystallite size and magnetization of gamma-Fe2O3/lys MNPs was
      found to be 14.5 nm, 40.6 emu/gm respectively. The surface functionalization by L
      lysine amino acid and metal-ligand bonding was also confirmed by FTIR
      spectroscopy. The hydrodynamic diameter, colloidal stability and surface charge
      on MNPs were characterized by DLS and zeta potential analyser.

PMID- 22962802
TI  - Surface properties of thin gold layers sputtered on polymers.
AB  - Thin gold layers were sputtered on the foils of polypropylene-PP,
      polyethyleneterephthalate-PET, polystyrene-PS, polyethylene-PE and
      polytetrafluoroethylene-PTFE modified by Ar+ plasma. Surface properties of
      pristine, plasma treated and gold coated polymers were characterized by two
      points method (sheet electrical resistance), electrokinetical analysis (zeta
      potential, surface chemistry), goniometry (contact angle), electron paramagnetic
      resonance (concentration of radicals), atomic force microscopy (AFM, surface
      morphology and roughness) and scratch test (mechanical properties). Zeta
      potential and contact angle, as assumed, differ dramatically for plasma treated
      polymers and for the polymers deposited by Au layers. AFM images indicate that
      after gold deposition on polymers the surface roughness and the surface
      morphology change depending on pristine polymer surfaces (roughness and
      morphology) and sputtering time. Electrical measurements resulted in fact that
      with increasing layer thickness, the sheet resistance of the gold layer decreases
      for all polymers with increasing sputtering time. Lower adhesive destruction is
      observed on the gold layer deposited on plasma treated PE in comparison with
      pristine.

PMID- 22962803
TI  - Graphite nanoplatelets/multiwalled carbon nanotubes hybrid nanostructure for
      electrochemical capacitor.
AB  - Recently, the focus on carbon based nanostructures for various applications has
      been due to their novel properties such as high electrical conductivity, high
      mechanical strength and high surface area. In the present work, we have
      investigated the charge storage capacity of modified graphite nanoplatelets and
      hybrid structure of graphite nanoplatelets-multiwalled carbon nanotubes (MWNTs).
      These MWNTs can be used as spacers to reduce the possibility of restacking of
      graphite nanoplatelets and hence increases the surface area of the hybrid carbon
      nanostructure thereby high degree of metal oxide decoration is achieved over the
      hybrid structure. MWNTs were prepared by catalytic chemical vapor deposition
      technique and further purified with air oxidation and acid treatment. Graphite
      was treated with conc. nitric acid and sulphuric acid in the volumetric ratio of
      1:3 for 3 days and these modified graphite nanoplatelets were further stirred
      with MWNTs in equal weight ratio to form hybrid nanostructure. Further, ruthenium
      oxide (RuO2) nanoparticles were decorated on this hybrid structure using chemical
      route followed by calcination. RuO2 decorated hybrid carbon nanostructure was
      characterized by using X-ray diffraction, Electron microscopy and Raman
      spectroscopy. The performance of the hybrid structure based nanocomposite as
      electrochemical capacitor electrodes was analyzed by studing its capacitive and
      charge-discharge behaviours using cyclic voltammetry and chronopotentiometry
      techniques and the results have been discussed.

PMID- 22962804
TI  - Plasma-modified and polyethylene glycol-grafted polymers for potential tissue
      engineering applications.
AB  - Modified and grafted polymers may serve as building blocks for creating
      artificial bioinspired nanostructured surfaces for tissue engineering.
      Polyethylene (PE) and polystyrene (PS) were modified by Ar plasma and the surface
      of the plasma activated polymers was grafted with polyethylene glycol (PEG). The
      changes in the surface wettability (contact angle) of the modified polymers were
      examined by goniometry. Atomic Force Microscopy (AFM) was used to determine the
      surface roughness and morphology and electrokinetical analysis (Zeta potential)
      characterized surface chemistry of the modified polymers. Plasma treatment and
      subsequent PEG grafting lead to dramatic changes in the polymer surface
      morphology, roughness and wettability. The plasma treated and PEG grafted
      polymers were seeded with rat vascular smooth muscle cells (VSMCs) and their
      adhesion and proliferation were studied. Biological tests, performed in vitro,
      show increased adhesion and proliferation of cells on modified polymers. Grafting
      with PEG increases cell proliferation, especially on PS. The cell proliferation
      was shown to be an increasing function of PEG molecular weight.

PMID- 22962805
TI  - Tuning of magnetic dipolar interactions of maghemite nanoparticles embedded in
      polyelectrolyte layer-by-layer films.
AB  - In this study we report an experimental approach capable of tuning dipolar
      interactions in hybrid magnetic nanofilms produced via layer-by-layer assembly of
      positively-charged maghemite nanoparticles and sodium sulfonated polystyrene onto
      glass and silicon substrates. Morphological and magnetic properties of the as
      prepared nanofilms were determined by Raman spectroscopy, atomic force
      microscopy, conventional and SQUID magnetometry. Maghemite nanoparticles form
      densely packed layers with voids between particles being filled by polymeric
      material as observed in atomic force microscopy images. Magnetic hysteresis loops
      and zero-field-cooled/field-cooled magnetization curves reveal a
      superparamagnetic behavior at room temperature. The energy barrier for the
      magnetic moment reversal of the nanofilms has been determined from the frequency
      dependent ac susceptibility and is related to the gamma-Fe2O3 nanoparticles
      concentration used in the colloidal dispersion throughout film fabrication.
      Variations on the interparticle distances have a direct effect on the
      interparticle dipolar interactions. A less concentrated colloid gives rise to
      large separated nanoparticles inside the nanofilm with a consequent reduction on
      the energy barrier for the magnetic moment reversal. The fabrication process
      exploring the control of the nanoparticle concentration can thus be used to tune
      the magnetic dipolar interactions in the nanofilms.

PMID- 22962806
TI  - Low solvothermal synthesis and characterization of hollow nanospheres molybdenum
      sulfide.
AB  - Hollow nanospheres of molybdenum disulfide have been synthesized by a novel
      solvothermal method under low temperature (180 degrees C). These nanomaterials
      were characterized by X-ray diffraction (XRD), Fourier transformation infra-red
      spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM, HRTEM) and X-ray Photoelectron Spectroscopy (XPS). A mechanism
      for the synthesis reaction is tentatively proposed and discussed.

PMID- 22962807
TI  - Graphene oxide and hydroxyapatite as fillers of polylactic acid nanocomposites:
      preparation and characterization.
AB  - Graphene and its derivatives have attracted great research interest for their
      potential applications in electronics, energy, materials and biomedical areas.
      When incorporated appropriately, these atomically thin carbon sheets are expected
      to improve physical properties of host polymers at extremely small loading.
      Herein, we report a novel two-step method for the preparation of
      PLLA/Hap/graphene oxide nanocomposites with augmented mechanical properties when
      compared to PLLA/Hap and neat PLLA. The presence of graphene oxide (GO) had a
      positive effect on the dispersion of hydroxyapatite particles on the polymeric
      matrix contributing for a good homogeneity of the final nanocomposite. PLLA
      nanocomposites prepared with 30% (w/w) of Hap and 1% (w/w) of GO showed the
      highest hardness and storage modulus values indicating an efficient load transfer
      between the fillers and the PLLA matrix. These materials may find interesting
      biomedical applications as for example bone screws. The following step on the
      study of these materials will be in vitro tests to access the biocompatibility of
      these new nanocomposites.

PMID- 22962808
TI  - Laser diffraction and electron microscopy studies on inhalable liposomes
      generated from particulate-based proliposomes within a medical nebulizer.
AB  - Particulate-based proliposomes were made by coating sucrose carrier particles
      with egg phosphatidylcholine (EPC), soya phosphatidylcholine (SPC) or soya
      phosphatidylcholine with an equimole ratio of cholesterol (SPC:Chol, 1:1).
      Inhalable multilamellar liposomes were generated from proliposomes in situ within
      a Pari LC Plus nebulizer by addition of aqueous phase, with no need for prior
      manual shaking. All proliposome formulations produced high aerosol and
      phospholipid outputs and were delivered in high fractions to the lower stage of a
      two-stage impinger. The SPC:Chol (1:1) liposomes tended to accumulate more in the
      nebulizer because of their greater rigidity, which correlated with the larger
      size measured at the end of nebulization. The size of aerosol droplets as
      measured by laser diffraction was similar for all formulations, however, at the
      sputtering period, the SPC:Chol (1:1) formulation produced large droplets with
      broadened size distribution. This study has demonstrated a simple approach to
      delivering high outputs of liposomes using a particulate-based proliposome
      technology and has shown an evidence of liposome generation from proliposomes
      within a medical nebulizer.

PMID- 22962809
TI  - Nanocrystalline diamond coating on non-planar silicon substrates.
AB  - Micro and nanosystems-based products will be an important contributor to the
      industrial and economic future, as a key value adding element for many sectors.
      The adoption of micro and nano manufacturing technologies making use of a variety
      of materials, components and knowledge based technologies will most probably
      provide functionality and intelligence to highly miniaturised systems. Chemical
      Vapour Deposited (CVD) diamond is a hard material of high mechanical strength and
      thermal stability and therefore an ideal candidate for microelectromechanical
      devices. The latter, is already being used to manufacture sensors, resonators,
      actuators, biological devices or even plastic moulding impressions, by depositing
      the film on a structured substrate, by selective growth of diamond on Si using
      SiO2 masks, or by pattern etching on oxygen-containing plasma. The diamond
      shaping may also be performed by a fine tuning of the nucleation and growth
      process. In this paper, it is presented the results of diamond coated structures
      and an evaluation of its morphology variation with the substrate configuration.
      The grown films were characterized for quality, surface roughness and
      microstructure using scanning electron microscopy, Raman and X-ray diffraction
      spectroscopy and surface profilometry.

PMID- 22962810
TI  - Reversible aggregation and chemical resistance of magnetic nanoclusters for their
      recycling and repetitive use in industrial bioprocesses.
AB  - Magnetic nanoclusters are widely used as carriers for biomedical and
      bioindustrial applications. The chemical resistance of the nanoclusters is a key
      factor for the recycling the magnetic beads for a repetitive use in the
      industrial bioprocesses. In this work, a study of the chemical resistance of
      Fe2O3 silica-coated nanoclusters at different pH is presented. The use of
      Horizontal Low Gradient Magnetic Field (HLGMF) for the control and separation of
      the magnetic nanoclusters at diferent magnetic field gradients is also
      investigated. For these purposes Fe2O3 silica-coated nanoclusters are synthesised
      and characreized by SQUID, TEM, Zeta potential techniques. The magnetophoresis
      study was performed at 15 T/m and 30 T/m magnetic field gradients. Recycling
      aspects of the nanoclusters were estimated by evaluating their resistance to pH
      variation from acid to basic solutions of about pH 2.5 and 10.

PMID- 22962811
TI  - Various nanostructures on macroscopically large areas prepared by tunable ion
      swelling.
AB  - Various nanostructures were fabricated by ion irradiation on large area (100) Si
      surfaces covered by colloidal Langmuir-Blodgett films as nanolithographic masks.
      The ordered structure of the Langmuir-Blodgett monolayer composed from spherical
      Stober silica particles of 200 nm and 450 nm diameter offer the possibility to
      form local surface swelling patterns during the ion bombardment step. Utilizing
      the dependence of the surface morphology on the irradiation parameters the
      tunability of nanostructuring was studied for 40 keV Ar+ and 500 keV Xe2+ ions.
      We show that the periodicity of the resulted surface pattern is determined by the
      size of the masking particles, while the height of nanostructures can be tuned by
      the ion fluence. The quality of projection of the nanomask contours to the
      substrate-the contrast of masking-can be set by choosing appropriate ion energy,
      thereby determining the curvature of the surface pattern. Moreover, deformation
      of the nanomask due to ion-nanoparticle interactions should be taken into account
      since these effects can be also utilized for tailoring various structures. The
      silica masking layers before and after ion irradiation and the resulting Si
      surface patterns were investigated by field emission scanning electron microscopy
      and atomic force microscopy analysis.

PMID- 22962812
TI  - Cerium oxide dispersed multi walled carbon nanotubes as cathode material for
      flexible field emitters.
AB  - Nanomaterials based electron sources are omnipresent in modern flat panel
      displays. Multi walled carbon nanotubes (MWNT) are the well studied electron
      emitter among the carbon materials. Since the surface modification of MWNT with
      low work function materials would have a positive impact on the field emission
      property of MWNT, cerium oxide (CeO2) nanoparticles dispersed multi walled carbon
      nanotubes (CeO2/MWNT) were synthesized by catalytic chemical vapour deposition
      followed by chemical reduction and its field emission property was investigated.
      The high-purity MWNT as well as CeO2/MWNT showed crystalline structure conformed
      by X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Further
      characterisation was done with Raman spectroscopy, UV-Visible absorption spectra
      and Fourier transform IR spectroscopy (FT-IR). The morphology and structural
      details of CeO2/MWNT composite was probed by field-emission scanning electron
      microscopy (FESEM) and energy dispersive X-ray analysis (EDX). The direct
      evidence of the formation of CeO2/MWNT composites was given by transmission
      electron microscopy (TEM). The synthesized sample was coated over a flexible
      carbon paper using spin coating technique. The experiment was performed under a
      vacuum of 1 x 10(-6) Torr and Fowler-Nordheim equation was used to analyse the
      data. The turn-on voltage for the cerium oxide dispersed MWNT was found for a
      current density of 10 microA/cm2. The emission current density from the CeO2
      nanoparticles dispersed MWNT reached 0.2 mA/cm2 at a reasonable bias field of
      2.58 V/microm. The results were compared with those of pure MWNT and pure CeO2
      nanoparticles with literature values.

PMID- 22962813
TI  - Characterization and cytocompatibility of carbon films.
AB  - Carbon layers on polyethyleneterephtalate (PET) backing were prepared by 3
      different deposition methods as evaporation, sputtering and photo induced
      chemical vapor deposition. UV-Vis, Raman spectroscopy, Rutherford backscattering
      techniques, goniometry and electrical resistance measurement were used for the
      characterization of the layers. Surface morphology of the layers was determined
      by AFM technique and the thickness was determined by SEM and profilometry.
      Adhesion and proliferation of 3T3 cells by method in vitro were studied. It was
      found that the properties of the deposited carbon layer depend on the deposition
      method. The layers prepared by sputtering are composed from oxidized amorphous
      carbon in the form of disordered graphite. Contact angle of deposited carbon
      layers decreases in comparison to pristine PET. The electrical resistance of
      carbon layer also decreases, a dramatic decrease being observed especially after
      carbon flash evaporation. The carbon deposition has no significant influence on
      surface roughness, but the surface morphology is strongly influenced. Adhesion of
      3T3 fibroblast didn't show any significant difference between PET, sputtered and
      CVD layers. Proliferation of 3T3 fibroblast has shows differences due to the
      surface morphology and also wettability of the surface which is linked to the
      chemical composition.

PMID- 22962814
TI  - Direct nucleation of silver nanoparticles on graphene sheet.
AB  - Silver (Ag) nanoparticles were synthesized on the surface of graphene sheet by
      the simultaneous reduction of Ag+ and graphene oxide (GO) in the presence of
      simple reducing agent, hydrazine hydrate (N2H4 x H2O). Both the Ag+ and GO were
      reduced and Ag+ was nucleated onto graphene. GO flakes were prepared by
      conventional chemical exfoliation method and in the presence of strong acidic
      medium of potassium chlorate. Silver nanoparticles were prepared using 0.01 M
      AgNO3 solution. The reduced GO sheet decorated with Ag is referred as G-Ag
      sample. G-Ag was characterized by FTIR (Fourier transform infrared) spectroscopy
      using GO as standard. An explicit alkene peak appeared around 1625 cm(-1) was
      observed in G-Ag sample. Besides, the characteristic carbonyl and hydroxyl peaks
      shows well reduction of GO. The FTIR therefore confirms the direct interaction of
      Ag into Graphene. SEM (scanning electron microscopy) and TEM (transmission
      electron microscopy) analysis were performed for morphological probing. The
      average size of Ag nanoparticles was confirmed by around 5-10 nm by the high
      resolution TEM (HRTEM). The Ag quantum dots incorporated nanocomposite material
      could become prominent candidate for diverse applications including photovoltaic,
      catalysis, and biosensors etc.

PMID- 22962815
TI  - Nonresonant detection of terahertz radiation in high-electron-mobility transistor
      structure using InAIAs/InGaAs/InP material systems at room temperature.
AB  - In this paper, we report on nonresonant detection of terahertz radiation using
      the rectification mechanism of two-dimensional plasmons in high-electron-mobility
      transistors using InAIAs/InGaAs/InP material systems. The experiments were
      performed at room temperature using a Gunn diode operating at 0.30 THz as the THz
      source. The measured response was dependent on the polarization of the incident
      THz wave; The device exhibited higher response when the electric-field vector of
      the incident radiation was directed in the source-drain direction. The 2D spatial
      distribution image of the transistor responsivity extracted from the measured
      response shows a clear beam focus centered on the transistor position, which
      ensures the appropriate coupling of the terahertz radiation to the device. The
      device also demonstrated excellent sensitivity/noise performances of
      approximately 125 V/W and approximately 10(-11) W/Hz(0.5) under 0.30 THz
      radiation.

PMID- 22962816
TI  - Synthesis of high concentration colloid solution of silica-coated AgI
      nanoparticles.
AB  - Methods for high concentration silica-coated silver iodide (AgI/SiO2) particles,
      which could be practically used as X-ray contrast agent, were examined. The first
      was a single-step method, which was to prepare AgI nanoparticles at an AgI
      concentration of 5 x 10(-3) M and coat the AgI nanoparticles with silica shell by
      a Stober method. The second was a multiple-step method, which was to repeat a
      step for preparing a AgI/SiO2 particle colloid solution with 10(-3) M AgI 5 times
      for adjusting a final AgI concentration to 5 x 10(-3) M. In the two methods,
      dominant particle aggregation took place, though core-shell particles were also
      produced. The third was a salting-out method, which was to salt out AgI/SiO2
      particles in their colloid solution prepared at an AgI concentration of 10(-3) M,
      remove supernatant by decantation, and redisperse the particles in a fresh
      solvent. Consequently, AgI/SiO2 particles with an AgI concentration as high as
      0.05 M were successfully prepared with the salting-out method, and their core
      shell structure was not damaged during the salting-out.

PMID- 22962817
TI  - Fabrication of poly(lactic acid)-poly(ethylene oxide) electrospun membranes with
      controlled micro to nanofiber sizes.
AB  - Biodegradable poly(L-lactide acid) (PLLA) nanofiber membranes were prepared by
      electrospinning of PLLA and poly(ethylene oxide) (PEO). The selective removal of
      PEO by water allows to obtain smaller fiber diameters and to increase the
      porosity of the membranes in comparison to PLLA membranes obtained under the same
      electrospinning conditions. After removal of PEO membranes with fiber sizes of
      260 nm and average porosity close to 80% are obtained. Thermal and infrared
      results confirm the poor miscibility of PLLA and PEO, with the PEO randomly
      distributed along the PLLA fibers. On the other, PLLA and PEO mixing strongly
      affect their respective degradation temperatures. The influence of the PEO in the
      electrospinning process is discussed and the results are correlated to the
      evolution of the PLLA fiber diameter.

PMID- 22962818
TI  - P-type Cuox thin films by rf-plasma enhanced reactive thermal evaporation:
      influence of rf-power density.
AB  - Copper oxide is a well known p-type semiconductor material, usually obtained by
      thermal oxidation of copper thin-films within few minutes, at atmospheric
      pressure. In this paper, thin films of copper oxide that were deposited by radio
      frequency plasma enhanced reactive thermal evaporation of copper at room
      temperature, without any post-deposition annealing treatment, are studied. The
      deposition of good quality p-type semiconductor oxide to be used in the
      fabrication of p-TFTs is the purpose of this work. The thickness of the films
      varies from 97 up to 160 nm. The influence of rf power density on chemical,
      electrical and optical properties of the films was studied. Samples present
      conductivity within the range of 6 x 10(-5) to 4 x 10(2) omega(-1) x cm(-1)
      (thermal activation energy in the interval 0.46 to 0.01 eV). The p-type
      conductivity of the films was confirmed by Seebeck effect in the more conductive
      samples. Surface composition obtained by XPS analysis was correlated with optical
      and electrical properties, showing that rf-power plays a main role in changes of
      material characteristics.

PMID- 22962819
TI  - The need for nano-scale modeling in solid oxide fuel cells.
AB  - Solid oxide fuel cells (SOFCs) are high temperature fuel cells, which are being
      developed for large scale and distributed power systems. SOFCs promise to provide
      cleaner, more efficient electricity than traditional fossil fuel burning power
      plants. Research over the last decade has improved the design and materials used
      in SOFCs to increase their performance and stability for long-term operation;
      however, there are still challenges for SOFC researchers to overcome before SOFCs
      can be considered competitive with traditional fossil fuel burning and renewable
      power systems. In particular degradation due to contaminants in the fuel and
      oxidant stream is a major challenge facing SOFCs. In this paper we discuss
      ongoing computational and experimental research into different degradation and
      design issues in SOFC electrodes. We focus on contaminants in gasified coal which
      cause electrochemical and structural degradation in the anode, and chromium
      poisoning which affects the electrochemistry of the cathode. Due to the complex
      microstructures and multi-physics of SOFCs, multi-scale computational modeling
      and experimental research is needed to understand the detailed physics behind
      different degradation mechanisms, the local conditions within the cell which
      facilitate degradation, and its effects on the overall SOFC performance. We will
      discuss computational modeling research of SOFCs at the macro-, meso- and nano
      scales which is being used to investigate the performance and degradation of
      SOFCs. We will also discuss the need for a multi-scale modeling framework of
      SOFCs, and the application of computational and multi-scale modeling to several
      degradation issues in SOFCs.

PMID- 22962820
TI  - Non-homogeneity of distribution of transport and trapping states in poly[2
      methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene].
AB  - Carrier transport and trapping was investigated in poly[2-methoxy-5-(3',7'
      dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) layers by thermally
      stimulated currents (TSC) depending on the exciting light spectral range. The
      upper edge of the spectra ranged from 1.77 eV up to 3.1 eV to assure selective
      excitation of the defect states. The TSC curves were shown to be a superposition
      of several thermally activated processes, i.e., carrier generation from trapping
      states and thermally stimulated mobility growth according to the Gaussian
      disorder model. The extrinsic excitation resulted in 0.15 eV photoconductivity
      effective activation energy values, which decreased down to 0.05 eV for the
      intrinsic excitation. The deeper states with activation energies of 0.28-0.3 eV
      and 0.8-0.85 eV were identified too. The results are direct indication by photo
      thermo-electrical methods of distributed in energy trapping and transport states
      with the standard deviation of the density of states of about 0.015 eV.

PMID- 22962821
TI  - Production of nanometer-size GaAs nanocristals by nanosecond laser ablation in
      liquid.
AB  - This paper reports the formation and characterization of spherical GaAs quantum
      dots obtained by nanosecond pulsed laser ablation in a liquid (ethanol or
      methanol). The produced bare GaAs nanoparticles demonstrate rather narrow size
      distribution which depends on the applied laser power density (from 4.25 to 13.9
      J/cm2 in our experiments) and is as low as 2.5 nm for the highest power used. The
      absolute value of the average diameter also decreases significantly, from 13.7 to
      8.7 nm, as the laser power increases in this interval. Due to the narrow
      nanoparticle size dispersion achieved at the highest laser powers two absorption
      band edges are clearly distinguishable at about 1.72 and 3.15 eV which are
      ascribed to E0 and E1 effective optical transitions, respectively. A comparison
      of the energies with those known for bulk GaAs allows one to conclude that an
      average diameter of the investigated GaAs nanoparticles is close to 10 nm, i.e.,
      they are quantum dots. High resolution transmission electron microscopy (HRTEM)
      images show that the bare GaAs nanoparticles are nanocrystalline, but many of
      them exhibit single/multiple twin boundary defects or even polycrystallinity. The
      formation of the GaAs crystalline core capped with a SiO2 shell was demonstrated
      by HRTEM and energy dispersive X-ray (EDX) spectroscopy. Effective band edges can
      be better distinguished in SiO2 capped nanoparticles than in bare ones, In both
      cases the band edges are correlated with size quantum confinement effect.

PMID- 22962822
TI  - The effect of megavoltage radiation on polymeric materials to be used in
      biomedical devices.
AB  - For a number of biomedical applications, including the development of phantoms
      for quality control of radiotherapy treatments and dose determination, it is
      important to study the radiation response of the used materials, in order to
      distinguish the relevant dose distribution modifications from the artifacts
      caused by the phantom material when subjected to high dose irradiation. Beside
      the radiation response, those materials should have certain physical and chemical
      properties in order to be able to be used for the purposes described above, i.e.,
      mechanical hardness and inelasticity, chemically stability and nonreactive, among
      others. In this work, a wide range of polymeric materials were irradiated under
      megavoltage radiation using a radiotherapy linear accelerator. The irradiated
      materials were imaged using transmission X-ray tomography to determine if some
      radiation induced electronic density change could result in altered Hounsfield
      units. Furthermore, Raman Spectroscopy and X-ray Diffraction (XRD) techniques
      were used before and after irradiation in order to study any structural
      modification induced by the radiation. In addition, a special phantom simulating
      a breast treatment with two tangential beams has been fabricated and tested.

PMID- 22962823
TI  - Temperature dependence of the Henry's law constant for hydrogen storage in NaA
      zeolites: a Monte Carlo simulation study.
AB  - Grand canonical Monte Carlo simulations of hydrogen adsorption in zeolites NaA
      were carried out for a wide range of temperatures between 77 and 300 K and
      pressures up to 180 MPa. A potential model was used that comprised of three main
      interactions: van der Waals, coulombic and induced polarization by the electric
      field in the system. The computed average number of adsorbed molecules per unit
      cell was compared with available results and found to be in agreement in the
      regime of moderate to high pressures. The particle insertion method was used to
      calculate the Henry coefficient for this model and its dependence on temperature.

PMID- 22962824
TI  - Synthesis and characterization of ZnO nano and micro structures grown by low
      temperature spray pyrolysis and vapor transport.
AB  - In this work we present a systematic study of ZnO micro and nanostructures grown
      by spray pyrolysis (SP) and by physical vapour transport (PVT) on glass and c
      sapphire substrates at low temperatures. Optimised growth conditions have allowed
      to obtain homogeneous ZnO nanolayers composed of quasi-spherical nanoparticles in
      the range 2 to 8 nm by spray pyrolysis, while by PVT the selected growth
      conditions allow to produce a wide variety of morphologies (tripods, grains,
      arrows and wires) of nano and microsize dimension. Grazing incidence X-ray
      diffraction, field emission scanning electron microscopy (FE-SEM), high
      resolution transmission electron microscopy (HRTEM), selected area electron
      diffraction (SAED) and energy dispersive X-ray spectroscopy (EDX) were used as
      characterization techniques in the investigation of structural, morphological and
      compositional nature of these nanostructures in relation with the growth method.

PMID- 22962825
TI  - Studies of non-vacuum processing of Cu-chalcogenide thin films.
AB  - Cu-chalcogenide thin films were prepared using a two stage method: one step
      electrodeposition of CuISe and CIGSe, and the sulfurisation of CISe to prepare
      CISSe thin films. The films were deposited on different substrates: Mo and ITO
      coated glass. The optimum potentials for electrodeposition of CISe and CIGSe
      films were respectively selected in the range -400 to -550 mV and -650 to -700 mV
      (vs. SCE). The electrodeposited layers were firmly adhesive. The well known
      chalcopyrite structure appears after annealing at 400 degrees C under Argon for
      CISe. The band gap value deduced from the optical measurements is close to 1 eV.
      To increase this value, addition of gallium in the aqueous electrolytic solution
      was performed. A band gap value as high as 1.26 eV was recorded on the obtained
      CIGSe films. Sulfurisation of CISe layers under 5% H2S/Ar atmosphere lead to a
      shift of the position of the principal XRD peaks indicating the substitution of
      selenium atoms by sulfur atoms and thus the formation of the quaternary CISSe.
      Optical measurements performed on this quaternary compound show that our films
      exhibit a band gap value scaling from 1 eV to 1.4 eV depending on the amount of
      sulphur incorporated into the layers during the heat treatments.

PMID- 22962826
TI  - Effect of zeolite content in the electrical, mechanical and thermal degradation
      response of poly(vinylidene fluoride)/NaY zeolite composites.
AB  - Polymer based composites of a-PVDF doped with different NaY zeolite
      (Na53Al53Si139O384) content were investigated. A good dispersion of NaY zeolite
      within the polymer matrix is achieved. The introduction of NaY nanoparticles
      enhance the storage modulus and the dielectric constant at room temperature. The
      dielectric constant at room temperature increases up to the value of 500 for the
      32 wt% composite, at 1 kHz. The increase of the dielectric constant is mainly
      attributed to interfacial polarization effects. For increasing zeolite content,
      the nanocomposite conductivity shows two conducting regimes separted by the so
      called breaking voltage, which is associated to an intrazeolite charge transport.
      Thermogravimetric results show that the introduction of zeolites affects the
      thermal degradation of the polymer for low zeolite contents and also indicate the
      presence of water that also plays an important role in the electrical response of
      the materials.

PMID- 22962827
TI  - Integration of dye-sensitized solar cells, thermoelectric modules and electrical
      storage loop system to constitute a novel photothermoelectric generator.
AB  - This study self-develops a novel type of photothermoelectric power generation
      modules. Dye-sensitized solar cells (DSSCs) serve as the photoelectric conversion
      system and a copper (Cu) heat-transfer nanofilm coating on both sides of the
      thermoelectric generator (TEG) acts as a thermoelectric conversion system. Thus
      module assembly absorbs light and generates electricity by DSSCs, and also
      recycles waste heat and generates power by the TEG. In addition, a set of
      pulsating heat pipes (PHP) filled with Cu nanofluid is placed on the cooling side
      to increase cooling effects and enhance the power generation efficiency. Results
      show that when the heat source of thermoelectric modules reaches 90 degrees C,
      TEG power output is increased by 85.7%. Besides, after thermoelectric modules are
      heated by additional heat source at 80 degrees C, the electrical energy generated
      by them can let a NiMH cell (1.25 V) be sufficiently charged in about 30 minutes.
      When photothermoelectric modules is illumined by simulated light, the temperature
      difference of two sides of TEG can reach 7 degrees C and the thermoelectric
      conversion efficiency is 2.17%. Furthermore, the power output of the
      thermoelectric modules is 11.48 mW/cm2, enhancing 1.4 % compared to merely using
      DSSCs module.

PMID- 22962828
TI  - Eco-friendly hybrid pigments made of cellulose and iron oxides.
AB  - The controlled hydrolysis of FeC2O4 in the presence of vegetable cellulose fibres
      was investigated to produce a pallet of cellulose/iron oxide hybrid colored
      materials. Distinct iron oxide phases have been deposited at the cellulose fibres
      surfaces by varying the relative amount of FeC2O4 and NaOH, here used as starting
      materials, by performing the synthesis in hydrothermal conditions. This is a new
      chemical strategy for the production of a number of hybrid materials whose
      coloristic properties have been evaluated aiming their potential use as novel
      pigments for polymer based products.

PMID- 22962829
TI  - Tuning the conditions for the deposition of nanocrystalline diamond by hot
      filament chemical vapour deposition.
AB  - Although large focus has been placed into the deposition of nanocrystalline and
      ultra-nanocrystalline diamond films, most of this research uses microwave plasma
      assisted CVD systems. However, the growth conditions used in microwave systems
      cannot be directly used in hot-filament CVD systems. This paper, aims to enlarge
      the knowledge of the diamond film depositing process. H2/CH4/Ar gas mixtures have
      been used to deposit micro, nano and ultra-nanocrystalline diamond films by hot
      filament CVD systems. Additionally, the distance between the filaments array and
      the substrate was varied, in order to observe its effect and consequently the
      effect of a lower substrate temperature in the nucleation density and deposition.
      All the samples were characterized for microstructure and quality, using scanning
      electron microscopy and Raman spectroscopy.

PMID- 22962830
TI  - Effect of the drying conditions on the microstructure of silica based xerogels
      and aerogels.
AB  - Nanostructured silica based xerogels and aerogels are prepared by sol-gel
      technology, using methyltrimethoxysilane as precursor. The influence of the
      drying method and conditions on the microstructure of the obtained materials is
      investigated, since the drying stage has a critical influence on their porosity.
      Two types of drying methods were used: atmospheric pressure drying (evaporative),
      to produce xerogels, and supercritical fluids drying, to obtain aerogels.
      Although the supercritical fluids drying technique is more expensive and
      hazardous than the atmospheric pressure drying, it is well known that aerogels
      are less dense than the xerogels due to less pore shrinkage. However, the ideal
      situation would be to use atmospheric pressure drying in conditions that minimize
      the pore collapse. Therefore, in this work, different temperature cycles for
      atmospheric pressure drying and two heating rates for the supercritical fluids
      drying are tested to study the gels' shrinkage by analyzing the density and
      porosity properties of the final materials. The best materials obtained are
      aerogels dried with the lower heating rate (approximately 80 degrees C/h), since
      they exhibit very low bulk density (approximately 50 kg/m3), high porosity (95%)
      mainly micro and mesopores, high surface area (approximately 500 m2/g), moderate
      flexibility and a remarkable hydrophobic character (>140 degrees). It was proved
      that the temperature cycles of atmospheric pressure drying can be tuned to obtain
      xerogels with properties comparable to those of aerogels, having a bulk density
      only approximately15 kg/m3 higher. All the synthesized materials fulfill the
      requirements for application as insulators in Space environments.

PMID- 22962831
TI  - Nanocrystalline diamond coatings for mechanical seals applications.
AB  - A mechanical seal is a type of seal used in rotating equipment, such as pumps and
      compressors. It consists of a mechanism that assists the connection of the
      rotating shaft to the housings of the equipments, preventing leakage or avoiding
      contamination. A common cause of failure of these devices is end face wear out,
      thus the use of a hard, smooth and wear resistant coating such as nanocrystalline
      diamond would be of great importance to improve their working performance and
      increase their lifetime. In this paper, different diamond coatings were deposited
      by the HFCVD process, using different deposition conditions. Additionally, the as
      grown films were characterized for, quality, morphology and microstructure using
      scanning electron microscopy (SEM) and Raman spectroscopy. The topography and the
      roughness of the films were characterized by atomic force microscopy (AFM).

PMID- 22962832
TI  - Tribological behaviour of mechanically synthesized titanium-boron carbide
      nanostructured coating.
AB  - In this paper, titanium-boron carbide (Ti/B4C) nanocomposite coatings with
      different B4C nanoparticles contents were fabricated by surface mechanical
      attrition treatment (SMAT) method by using B4C nanoparticles with average
      nanoparticle size of 40 nm. The characteristics of the nanopowder and coatings
      were evaluated by microhardness test, scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). Friction and wear performances of
      nanocomposite coatings and pure titanium substrate were comparatively
      investigated, with the effect of the boron carbide content on the friction and
      wear behaviours to be emphasized. The results show the microhardness, friction
      and wear behaviours of nanocomposite coatings are closely related with boron
      carbide nanoparticle content. Nanocomposite coating with low B4C content shows
      somewhat (slight) increased microhardness and wear resistance than pure titanium
      substrate, while nanocomposite coating with high B4C content has much better
      (sharp increase) wear resistance than pure titanium substrate. The effect of B4C
      nanoparticles on microhardness and wear resistance was discussed.

PMID- 22962833
TI  - Nanoparticle dispersion and electroactive phase content in polyvinylidene
      fluoride/Ni0.5Zn0.5Fe2O4 nanocomposites for magnetoelectric applications.
AB  - Ni0.5Zn0.5FeO4 ferrite/polyvinylidene fluoride composite films were prepared by a
      solution method and melt processing. As nanoparticle dispersion and polymer
      electroactive phase content are some of the key factors for improving
      magnetoelectric coupling in the composites, the dispersion of ferrite
      nanoparticles in the polymeric matrix was studied by preparing samples by two
      alternative dispersion routes: ultrasound and citric acid nanoparticle
      surfactation. The nucleation of the electroactive beta-phase of the polymer was
      observed in composites produced by nanoparticle dispersion by ultrasound. This
      fact avoids the need of stretching composites at elevated temperature in order to
      obtain the electroactive phase and obtain magnetoelectric composites. By this
      method, nevertheless, large nanoparticle agglomerates are obtained. Nanoparticle
      dispersion is largely improved by citric acid surfactation of the nanoparticles.
      On the other hand, the beta-phase of the polymer is not nucleated due to the
      modification of the nanoparticle-polymer interaction due to the presence of the
      surfactant.

PMID- 22962834
TI  - Ferromagnetic order in aged Co-doped TiO2 anatase nanopowders.
AB  - This paper reports on the ferromagnetic properties of aged Ti(1-x)CoxO(2-delta)
      anatase nanopowders with different Co contents (0.03 < or = x < or = 0.10). It is
      shown for the first time that aged Co:TiO2 anatase samples retain rather high
      values of magnetization (M), remanence (Mr) and coercivity (Hc) which provide
      strong evidence for a preserved long-range ferromagnetic order. Room temperature
      M, Mr and Hc values were measured in the ranges of [0.05, 0.79] microB/Co,
      [0.044, 0.096] microB/Co and [366.7,494.8]Oe, respectively, which are in the same
      range as in general reported either for newly prepared thin films or
      nanoparticles.

PMID- 22962835
TI  - Micro structuration of gaas surface by wet etching: towards a specific surface
      behavior.
AB  - Resonant microelectromechanical systems are promising devices for real time and
      highly sensitive measurements. The sensitivity of such sensors to additional mass
      loadings which can be increased thanks to the miniaturisation of devices is of
      prime importance for biological applications. The miniaturisation of structures
      passes through a photolithographic process and wet chemical etching. So, this
      paper presents new results on the anisotropic chemical etching of the gallium
      arsenide (GaAs) crystal used for this application, in several solutions. This
      paper focuses on the micro/nanostructuration of the sensing surface to increase
      the sensor sensitivity. Indeed, this active surface will be biofunctionalized to
      operate in biological liquid media in view of biomolecules detection. Several
      experimental conditions of etching bath composition, concentration and
      temperature were examined to obtain a large variety of geometrical surfaces
      topographies and roughness. According to the orientation dependence of the
      chemical etching process, the experiments were also performed on various GaAs
      crystal plates. The bath 1 H3PO4:9 H2O2:1 H2O appeared to be particularly adapted
      to the fabrication of the GaAs microstructured membrane: indeed, the bath is
      highly stable, anisotropic, and, as a function of temperature, it allows the
      production of a large variety of GaAs surface topographies.

PMID- 22962836
TI  - Characterization of silicon surfaces implanted with antimony ions and submitted
      to annealing and ageing treatments.
AB  - In this work, we study the effect of annealing and ageing treatments on the
      behavior of antimony atoms implanted in Si(111) targets. The ion implantation was
      performed at 120 keV energy to a dose of 2.3 x 10(15) Sb+ cm(-2). Concerning the
      annealing treatment, it has been carried out at 900 degrees C during 30 minutes
      (under vacuum). The samples have been analyzed in two steps: immediately after
      their elaboration and after an ageing period of 4 years and 4 months. Several
      techniques have been applied for samples analysis: Rutherford backscattering
      spectroscopy (RBS), X-ray diffraction (XRD) and electrical measurements. Before
      the ageing period, a good recovery of radiation damage has been obtained and
      degrees 50% of the dopant was redistributed into substitutional silicon sites.
      However, degrees 22% of antimony has been lost from the Si substrates. After the
      ageing period, the fraction of substituted atoms remained unchanged but a
      quantity of approximately 20% has again been lost from the specimens. This
      quantity provided from antimony atoms which remained into irregular positions of
      Si lattice.

PMID- 22962837
TI  - Construction of long-wavelength-light photocurrent generation system based on
      self-assembled monolayer of cobaltadithiolene [60]fullerene complex.
AB  - [60]Fullerene pentaester and pentaacid derivatives bearing cobaltadithiolene dyes
      were successfully synthesized under mild reaction conditions. Self-assembled
      monolayers (SAMs) of the pentaacid derivative were prepared by an immersion
      method and the photocurrent generation properties of the SAMs were measured. Due
      to the introduction of the light-absorbing cobaltadithiolene moiety, the range of
      available wavelengths for photoelectric conversion was extended to lambda = 700
      nm, which is longer than that of conventional penta(organo)[60]fullerene
      carboxylic acids.

PMID- 22962838
TI  - Ultrasensitive flexible graphene based field-effect transistor (FET)-type
      bioelectronic nose.
AB  - Rapid and precise discrimination of various odorants is vital to fabricating
      enhanced sensing devices in the fields of disease diagnostics, food safety, and
      environmental monitoring. Here, we demonstrate an ultrasensitive and flexible
      field-effect transistor (FET) olfactory system, namely, a bioelectronic nose (B
      nose), based on plasma-treated bilayer graphene conjugated with an olfactory
      receptor. The stable p- and n-type behaviors from modified bilayer graphene
      (MBLG) took place after controlled oxygen and ammonia plasma treatments. It was
      integrated with human olfactory receptors 2AG1 (hOR2AG1: OR), leading to the
      formation of the liquid-ion gated FET-type platform. ORs bind to the particular
      odorant amyl butyrate (AB), and their interactions are specific and selective.
      The B-noses behave as flexible and transparent sensing devices and can recognize
      a target odorant with single-carbon-atom resolution. The B-noses are
      ultrasensitive and highly selective toward AB. The minimum detection limit (MDL)
      is as low as 0.04 fM (10(-15); signal-to-noise: 4.2), and the equilibrium
      constants of OR-oxygen plasma-treated graphene (OR-OG) and ammonia plasma-treated
      graphene (-NG) are ca. 3.44 * 10(14) and 1.47 * 10(14) M(-1), respectively.
      Additionally, the B-noses have long-term stability and excellent mechanical
      bending durability in flexible systems.

PMID- 22962839
TI  - A capacitance sensor for water: trace moisture measurement in gases and organic
      solvents.
AB  - The determination of water in various matrices is one of the most important
      analytical measurements. We report on a high-resolution capacitance-based
      moisture sensor utilizing a thin film of a perfluorosulfonate ionomer (PFSI)
      H(3)PO(4) composite in a flow-through configuration, for both gas and liquid
      samples. Incorporation of H(3)PO(4) into a PFSI sensing film improved the limit
      of detection (LOD) (signal-to-noise ratio, S/N = 3) by a factor of 16 in the gas
      phase to 0.075% relative humidity (RH) (dew point = -56  degrees C). The response
      time was dependent on the sensing film thickness and composition and was as low
      as ~60 ms. The temperature dependence of the sensor response, and its relative
      selectivity over alcohol and various other solvents, are reported. Measurement of
      water in organic solvents was carried out in two different ways. In one
      procedure, the sample was vaporized and swept into the detector (e.g., in a gas
      chromatograph (GC) without a column); it permitted a throughput of 80 samples/h.
      This is well-suited for higher (%) levels of water. In the other method, a flow
      injection analysis system integrated to a tubular dialysis membrane pervaporizer
      (PV-FIA) was used; the LOD for water in ethanol was 0.019% (w/w). We demonstrated
      the temporal course of drying of ethanol by Drierite; the PV-FIA results showed
      excellent correspondence (r(2) > 0.99) with results from GC-thermal conductivity
      detection. The system can measure trace water in many types of organic solvents;
      no reagent consumption is involved.

PMID- 22962844
TI  - Perchlorate production by photodecomposition of aqueous chlorine solutions.
AB  - Aqueous chlorine solutions (defined as chlorine solutions (Cl(2,T)) containing
      solely or a combination of molecular chlorine (Cl(2)), hypochlorous acid (HOCl),
      and hypochlorite (OCl(-))) are known to produce toxic inorganic disinfection
      byproduct (e.g., chlorate and chlorite) through photoactivated transformations.
      Recent reports of perchlorate (ClO(4)(-)) production-a well-known thyroid hormone
      disruptor- from stored bleach solutions indicates the presence of unexplored
      transformation pathway(s). The evaluation of this potential ClO(4)(-) source is
      important given the widespread use of aqueous chlorine as a disinfectant. In this
      study, we perform detailed rate analysis of ClO(4)(-) generation from aqueous
      chlorine under varying environmental conditions including ultraviolet (UV) light
      sources, intensity, solution pH, and Cl(2,T) concentrations. Our results show
      that ClO(4)(-) is produced upon UV exposure of aqueous chlorine solutions with
      yields ranging from 0.09 * 10(-3) to 9.2 * 10(-3)% for all experimental
      conditions. The amount of ClO(4)(-) produced depends on the starting
      concentrations of Cl(2,T) and ClO(3)(-), UV source wavelength, and solution pH,
      but it is independent of light intensity. We hypothesize a mechanistic pathway
      derived from known reactions of Cl(2,T) photodecomposition that involves the
      reaction of Cl radicals with ClO(3)(-) to produce ClO(4)(-) with calculated rate
      coefficient (k(ClO4-)) of (4-40) * 10(5) M(-1) s(-1) and (3-250) * 10(5) M(-1) s(
      1) for UV-B/C and UV-A, respectively. The measured ClO(4)(-) concentrations for
      both UV-B and UV-C experiments agreed well with our model (R(2) = 0.88-0.99),
      except under UV-A light exposure (R(2) = 0.52-0.93), suggesting the possible
      involvement of additional pathways at higher wavelengths. Based on our results,
      phototransformation of aqueous chlorine solutions at concentrations relevant to
      drinking water treatment would result in ClO(4)(-) concentrations (~0.1 MUg L(
      1)) much below the proposed drinking water limits. The importance of the
      hypothesized mechanism is discussed in relation to natural ClO(4)(-) formation by
      atmospheric transformations.

PMID- 22962845
TI  - Prototropic tautomerism and basic molecular principles of hypoxanthine
      mutagenicity: an exhaustive quantum-chemical analysis.
AB  - The molecular structures, relative stability order, and dipole moments of a
      complete family of 21 planar hypoxanthine (Hyp) prototropic molecular
      zwitterionic tautomers including ylidic forms were computationally investigated
      at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum and in
      three different surrounding environments: continuum with a low dielectric
      constant (epsilon = 4) corresponding to a hydrophobic interface of protein
      nucleic acid interactions, dimethylsulfoxide (DMSO), and water. The keto-N1HN7H
      tautomer was established to be the global minimum in vacuum and in continuum with
      epsilon = 4, while Hyp molecule exists as a mixture of the keto-N1HN9H and keto
      N1HN7H tautomers in approximately equal amounts in DMSO and in water at T =
      298.15 K. We found out that neither intramolecular tautomerization by single
      proton transfer in the Hyp base, nor intermolecular tautomerization by double
      proton transfer in the most energetically favorable Hyp.Hyp homodimer (symmetry
      C(2h)), stabilized by two equivalent N1H...O6 H-bonds, induces the formation of
      the enol tautomer (marked with an asterisk) of Hyp with cis-oriented O6H hydroxyl
      group relative to neighboring N1C6 bond. We first discovered a new scenario of
      the keto-enol tautomerization of Hyp . Hyp homodimer (C(2h)) via zwitterionic
      near-orthogonal transition state (TS), stabilized by N1+H...N1- and O6+H...N1- H
      bonds, to heterodimer Hyp* . Hyp (C(s)), stabilized by O6H...O6 and N1H...N1 H
      bonds. We first showed that Hyp* . Thy mispair (C(s)), stabilized by O6H...O4,
      N3H...N1, and C2H...O2 H-bonds, mimicking Watson-Crick base pairing, converts to
      the wobble Hyp . Thy base pair (C(s)), stabilized by N3H...O6 and N1H...O2 H
      bonds, via high- and low-energy TSs and intermediate Hyp . Thy*, stabilized by
      O4H...O6, N1H...N3, and C2H...O2 H-bonds. The most energetically favorable TS is
      the zwitterionic pair Hyp+ . Thy- (C(s)), stabilized by O6+H...O4-, O6+H...N3-,
      N1+H...N3-, and N1+H...O2- H-bonds. The authors expressed and substantiated the
      hypothesis, that the keto tautomer of Hyp is a mutagenic compound, while enol
      tautomer Hyp* does not possess mutagenic properties. The lifetime of the
      nonmutagenic tautomer Hyp* exceeds by many orders the time needed to complete a
      round of DNA replication in the cell. For the first time purine-purine planar H
      bonded mispairs containing Hyp in the anti-orientation with respect to the sugar
      moiety--Hyp . Ade(syn), Hyp . Gua*(syn), and Hyp . Gua(syn), that closely
      resembles the geometry of the Watson-Crick base pairs, have been suggested as the
      source of transversions. An influence of the surrounding environment (epsilon =
      4) on the stability of studied complexes and corresponding TSs was estimated by
      means of the conductor-like polarizable continuum model. Electron-topological,
      structural, vibrational, and energetic characterictics of all conventional and
      nonconventional H-bonds in the investigated structures are presented. Presented
      data are key to understanding elementary molecular mechanisms of mutagenic action
      of Hyp as a product of the adenine deamination in DNA.

PMID- 22962846
TI  - When role reversal and brokering meet: filial responsibility among young
      immigrants to Israel from the former Soviet Union.
AB  - Traditional conceptualizations of role reversal and brokering (language and
      cultural in immigration), in which children assume culturally atypical adult
      responsibilities, have developed as different scholarly domains, despite their
      theoretical similarity. The purpose of the present article is to increase the
      integration between the two bodies of literature to achieve a better
      understanding of filial responsibilities children assume upon immigration and
      their differential correlates with adjustment. The structure of filial
      responsibility in immigration, interrelations between its distinct components,
      and the ability of the brokering roles to add significantly to the predicting of
      adjustment are studied. Young adult immigrants from the former Soviet Union to
      Israel (n = 220) completed the Comprehensive Filial Responsibilities Inventory
      (CFRI), the Brief Symptom Inventory, and the self-efficacy inventory. Factor
      analysis identified six CFRI domains with satisfying psychometric properties. The
      factors are dominance in family, cultural brokering, language brokering,
      emotional support to parents, self-reliance, and money issues. Hierarchical
      regression analyses showed a contribution of the brokering roles to prediction of
      psychological distress above and beyond traditional roles. The results support
      the validity of the CFRI and contribute to the understanding of interrelations
      among the various filial responsibilities, including brokering roles.

PMID- 22962847
TI  - Work engagement supports nurse workforce stability and quality of care: nursing
      team-level analysis in psychiatric hospitals.
AB  - Research in healthcare settings reveals important links between work environment
      factors, burnout and organizational outcomes. Recently, research focuses on work
      engagement, the opposite (positive) pole from burnout. The current study
      investigated the relationship of nurse practice environment aspects and work
      engagement (vigour, dedication and absorption) to job outcomes and nurse-reported
      quality of care variables within teams using a multilevel design in psychiatric
      inpatient settings. Validated survey instruments were used in a cross-sectional
      design. Team-level analyses were performed with staff members (n = 357) from 32
      clinical units in two psychiatric hospitals in Belgium. Favourable nurse practice
      environment aspects were associated with work engagement dimensions, and in turn
      work engagement was associated with job satisfaction, intention to stay in the
      profession and favourable nurse-reported quality of care variables. The strongest
      multivariate models suggested that dedication predicted positive job outcomes
      whereas nurse management predicted perceptions of quality of care. In addition,
      reports of quality of care by the interdisciplinary team were predicted by
      dedication, absorption, nurse-physician relations and nurse management. The study
      findings suggest that differences in vigour, dedication and absorption across
      teams associated with practice environment characteristics impact nurse job
      satisfaction, intention to stay and perceptions of quality of care.

PMID- 22962848
TI  - Formation of hybrid hydrogels consisting of tripeptide and different silver
      nanoparticle-capped ligands: modulation of the mechanical strength of gel phase
      materials.
AB  - An N-terminally Boc (tert-butyloxycarbonyl) group-protected synthetic tripeptide
      (Boc-Phe-Phe-Ala-OH) has been found to form a translucent hydrogel in basic
      aqueous medium. This hydrogel material has been characterized using field
      emission scanning electron microscopy (FE-SEM), transmission electron microscopy
      (TEM), Fourier transformed infrared spectroscopy, differential scanning
      calorimetric, X-ray diffraction (XRD), and rheological studies. FE-SEM and TEM
      studies have revealed the formation of a nanofibrillar network structure upon
      gelation. Thiol (-SH) containing ligands (amino acid/peptide) have been used to
      stabilize small silver nanoparticles (AgNPs), and these thiol-capped silver
      nanoparticles have been incorporated into this hydrogel to prepare hybrid
      hydrogels. Morphological study of silver nanoparticles containing a hybrid
      hydrogel (using TEM experiments) has indicated the nice fabrication of AgNPs
      along the gel nanofibers. Fabrication of nanoparticles upon the gel nanofibers is
      due to noncovalent interactions between the capping ligands of the nanoparticles
      and the peptide-based hydrogel nanofibers. Rheological investigations of these
      hybrid hydrogels have shown the weakening of the mechanical strength of the
      hydrogel after incorporation of AgNPs within the native hydrogel system. Our
      studies have vividly shown the dependence of the elastic modulus (G') and yield
      stress (sigma(y)) on three factors: (a) the nature of the stabilizing ligands
      used for AgNPs, (b) the size of the AgNPs, and (c) the amount of AgNPs used for
      the preparation of hybrid hydrogel systems. Modulation of the mechanical strength
      of the hybrid hydrogel can be successfully achieved by varying these above
      mentioned factors. This modulation of the mechanical properties keeps a future
      promise to make tunable soft materials with interesting properties.

PMID- 22962850
TI  - Influence of leaf litter moisture on the efficiency of the Winkler method for
      extracting ants.
AB  - The Winkler extraction is one of the two fundamental sampling techniques of the
      standardized "Ants of the Leaf Litter" protocol, which aims to allow qualitative
      and quantitative comparisons of ant (Hymenoptera: Formicidae) assemblages. To
      achieve this objective, it is essential that the standard 48-hour extraction
      provides a reliable picture of the assemblages under study. Here, we tested to
      what extent the efficiency of the ant extraction is affected by the initial
      moisture content of the leaf litter sample. In an Ecuadorian mountain rainforest,
      the leaf litter present under rainfall-excluded and rainfall-allowed plots was
      collected, its moisture content measured, and its ant fauna extracted with a mini
      Winkler apparatus for a 48-hour and a 96-hour period. The efficiency of the
      Winkler method to extract ant individuals over a 48-hour period decreased with
      the moisture content of the leaf litter sample. However, doubling the extraction
      time did not improve the estimations of the ant species richness, composition,
      and relative abundance. Although the moisture content of the leaf litter slightly
      affected the ant sampling, our results indicated that a 48-hour Winkler
      extraction, as recommended by the "Ants of the Leaf Litter" protocol, is
      sufficient to allow reliable comparisons of ant assemblages.

PMID- 22962851
TI  - New method to access hyperbranched polymers with uniform structure via one-pot
      polymerization of inimer in microemulsion.
AB  - A facile approach is presented for successful synthesis of hyperbranched polymers
      with high molecular weight and uniform structure by a one-pot polymerization of
      an inimer in a microemulsion. The segregated space in the microemulsion confined
      the inimer polymerization and particularly the polymer-polymer reaction within
      discrete nanoparticles. At the end of polymerization, each nanoparticle contained
      one hyperbranched polymer that had thousands of inimer units and low
      polydispersity. The hyperbranched polymers were used as multifunctional
      macroinitiators for synthesis of "hyper-star" polymers. When a degradable inimer
      was applied, the hyper-stars showed fast degradation into linear polymer chains
      with low molecular weight.

PMID- 22962849
TI  - Cooperative interaction of MUC1 with the HGF/c-Met pathway during
      hepatocarcinogenesis.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) induced c-Met activation is known as
      the main stimulus for hepatocyte proliferation and is essential for liver
      development and regeneration. Activation of HGF/c-Met signaling has been
      correlated with aggressive phenotype and poor prognosis in hepatocellular
      carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported
      in most cancers. Many of the oncogenic effects of MUC1 are believed to occur
      through the interaction of MUC1 with signaling molecules. To clarify the role of
      MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact
      cooperatively and what their role(s) is in hepatocarcinogenesis. RESULTS: MUC1
      and c-Met over-expression levels were determined in highly motile and invasive,
      mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC
      tissues, and these levels were compared to those in normal liver tissues. Co
      expression of both c-Met and MUC1 was found to be associated with the
      differentiation status of HCC. We further demonstrated an interaction between c
      Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this
      interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation
      restored HGF-mediated MUC1 down-regulation, and decreased the migratory and
      invasive abilities of HCC cells via inhibition of beta-catenin activation and c
      Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met
      activation and HGF-induced cell motility and invasion. CONCLUSIONS: These
      findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide
      an advantage for invasion to HCC cells through the beta-catenin/c-Myc pathway.
      Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

PMID- 22962852
TI  - Associations between higher-level competence and general intelligence in
      community-dwelling older adults.
AB  - OBJECTIVES: Higher-level competence is crucial for healthy and socially
      independent living, and general intelligence may underlie heath status. The aim
      of this study was to elucidate associations between general intelligence and
      higher-level competence in elderly individuals without dementia. METHODS: A total
      of 207 community-dwelling elderly persons, aged 70-74 years, were enrolled. A
      personal interview was performed to obtain data on socio-demographic and medical
      factors; higher-level competence was evaluated using the Tokyo Metropolitan
      Institute of Gerontology index of competence (TMIG index). Raven's Coloured
      Progressive Matrices (RCPM) test was used to assess general intelligence.
      Correlations between the TMIG index, its subscale scores and the RCPM score were
      evaluated by Spearman's rank correlation coefficients. Ordinal regression models
      were conducted with the TMIG index and its subscales as the dependent variables,
      RCPM as the principal independent variable, and age, sex, type of household,
      employment status, educational background, chronic medical conditions and number
      of natural teeth as the potential independent variables. RESULTS: There were
      significant but weak positive correlations between total score on the TMIG index,
      scores on the intellectual activity and social role subscales and RCPM score. In
      ordinal regression models, RCPM and educational background were significantly
      associated with total score on the TMIG index and the intellectual activity
      subscale, and only RCPM was associated with the social role subscale score, after
      adjusting for other potential variables. CONCLUSION: General intelligence may be
      significantly associated with higher-level competence, especially with
      intellectual activity and social role subscales, in community-dwelling older
      adults.

PMID- 22962853
TI  - Self-medication behaviors among Japanese consumers: sex, age, and SES differences
      and caregivers' attitudes toward their children's health management.
AB  - BACKGROUND: Since 2009, when the revised Pharmaceutical Affairs Act was enacted
      in Japan, self-medication practices have increased. Because the concept of self
      medication was recently introduced in Japan, few studies exist on this topic.
      Therefore, it is necessary to explore how self-medication is practiced. This
      study examined Japanese consumers' self-medication practices and attitudes toward
      over-the-counter (OTC) medicines based on their sex, age, and socioeconomic
      status (SES). METHODS: The participants were 403 adults (Mage = 41.1 years, SD =
      16.22). A quota sampling method was employed based on age group, and participants
      completed an online questionnaire. RESULTS: Participants in the 20-29 age group
      reported medical costs as an obstacle in seeing a doctor; in contrast,
      transportation was a mitigating factor for elderly people. Regarding SES, people
      at lower SES levels chose to rest instead of seeing a doctor or purchasing over
      the-counter (OTC) medicines when sick. They also placed more value on national
      brand OTC medicines than private brands (likely due to advertisements). This
      finding suggests individuals with a low SES do not select OTC medicines based on
      their effects or ingredients. Regarding attitudes toward OTC medicines, Japanese
      participants seemed to be unaware of the potential for abuse and side effects
      associated with OTC medicines. Finally, in relation to caregivers' self
      medication practices for their children, the majority of participants reported
      taking their children to the hospital since children tend to receive free medical
      care. Furthermore, caregivers with a high educational background are more
      confident in being able to help manage their children's health. CONCLUSIONS: Our
      results suggest that health and medical discrepancies among Japanese consumers
      pose new social problems. In Japan, universal health care is available, but the
      cost of receiving medical care is not completely free of charge. Thus, we hope
      that the government will attempt to meet the various needs of patients and
      support their well-being. Consumers also have to be more independent and aware of
      their health management, as self-medication practices will continue to play a
      more significant role in healthcare. More research is needed to find ways to
      teach Japanese consumers/patients of both the benefits and risks of over-the
      counter (OTC) medicines.

PMID- 22962854
TI  - A Bayesian model of biases in artificial language learning: the case of a word
      order universal.
AB  - In this article, we develop a hierarchical Bayesian model of learning in a
      general type of artificial language-learning experiment in which learners are
      exposed to a mixture of grammars representing the variation present in real
      learners' input, particularly at times of language change. The modeling goal is
      to formalize and quantify hypothesized learning biases. The test case is an
      experiment (Culbertson, Smolensky, & Legendre, 2012) targeting the learning of
      word-order patterns in the nominal domain. The model identifies internal biases
      of the experimental participants, providing evidence that learners impose
      (possibly arbitrary) properties on the grammars they learn, potentially resulting
      in the cross-linguistic regularities known as typological universals. Learners
      exposed to mixtures of artificial grammars tended to shift those mixtures in
      certain ways rather than others; the model reveals how learners' inferences are
      systematically affected by specific prior biases. These biases are in line with a
      typological generalization-Greenberg's Universal 18-which bans a particular word
      order pattern relating nouns, adjectives, and numerals.

PMID- 22962855
TI  - Mitochondrial oxidative stress index, activity of redox-sensitive aconitase and
      effects of endogenous anti- and pro-oxidants on its activity in control,
      Alzheimer's disease and Swedish Familial Alzheimer's disease brain.
AB  - Efficient function of the mitochondrial respiratory chain and the citric acid
      cycle (CAC) enzymes is required for the maintenance of human brain function. A
      conception of oxidative stress (OxS) was recently advanced as a disruption of
      redox signalling and control. Mitochondrial OxS (MOxS) is implicated in the
      development of Alzheimer's disease (AD). Thus, both pro- and anti-oxidants of the
      human body and MOxS target primarily the redox-regulated CAC enzymes, like
      mitochondrial aconitase (MAc). We investigated the specific activity of the MAc
      and MOxS index (MOSI) in an age-matched control (Co), AD and Swedish Familial AD
      (SFAD) post-mortem autopsies collected from frontal cortex (FC) and occipital
      primary cortex (OC) regions of the brain. We also examined whether the
      mitochondrial neuroprotective signalling molecules glutathione, melatonin and 17
      beta-estradiol (17betaE) and mitochondrially active pro-oxidant neurotoxic
      amyloid-beta peptide can modulate the activity of the MAc isolated from FC and OC
      regions similarly or differently in the case of Co, AD and SFAD. The activity of
      redox-sensitive MAc may directly depend on the mitochondrial oxidant/antioxidant
      balance in age-matched Co, AD and SFAD brain regions.

PMID- 22962856
TI  - Alexithymia is associated with an augmenter profile, but not only: evidence for
      anticipation to arousing music.
AB  - It has been suggested that high alexithymia scorers have an 'augmenter' profile
      which amplifies their physiological and subjective responses to highly arousing
      stimuli. The aim of this study was to test this theory using several
      physiological measures. Participants listened to musical excerpts either in a
      'weak-to-strong' or a 'strong-to-weak' order of arousing levels of stimuli. The
      results show that alexithymia was associated with an augmenter profile for
      subjective reports for the most arousing stimulus and with stronger skin
      conductance level responses in the 'strong-to-weak' order. These results
      partially support the augmenter profile and reveal that alexithymia may be
      associated with higher anticipation for the most arousing excerpt.

PMID- 22962857
TI  - Multigroup Confirmatory Factor Analysis of the Cognitive Dysfunction
      Questionnaire: instrument refinement and measurement invariance across age and
      sex.
AB  - The study adopted Confirmatory Factor Analysis (CFA) to investigate the factorial
      structure and reduce the number of items of the Cognitive Dysfunction
      Questionnaire (CDQ). The analyses were based on data for a total of 1,115
      participants from population based samples (mean age: 63.0 +/- 14.5 years, range:
      25-95) randomly split into a refinement (N = 569) and a cross-validation (N =
      546) sample. Equivalence of the measurement and structural portions of the
      refined model was demonstrated across the refinement and cross-validation
      samples. Among competing models the best fitting and parsimonious model had a
      hierarchical factor structure with five first-order and one second-order general
      factor. For the final version of the CDQ, 20 items within five domains were
      selected (Procedural actions, Semantic word knowledge, Face recognition, Temporal
      orientation, and Spatial navigation). Internal consistency reliabilities were
      adequate for the total scale and for the subscales. Multigroup CFAs indicated
      measurement invariance across age and sex up to the scalar level. Finally, higher
      levels of cognitive dysfunction as reflected by CDQ scores were predicted by
      advancing age, fewer years of education, and with deficits in general cognitive
      functioning as reflected by scores on the Mini-Mental State Examination. In
      conclusion, the CDQ appears to be psychometrically sound and shows the expected
      relationships with variables known to be associated with cognitive dysfunction
      and dementia. Future studies should apply it among clinical groups to further
      test its usefulness.

PMID- 22962858
TI  - Cost-effectiveness of a tailored intervention designed to increase breast cancer
      screening among a non-adherent population: a randomized controlled trial.
AB  - BACKGROUND: Although the percentage of women who initiate breast cancer screening
      is rising, the rate of continued adherence is poor. The purpose of this study was
      to examine the effectiveness and cost-effectiveness of a tailored print
      intervention compared with a non-tailored print intervention for increasing the
      breast cancer screening rate among a non-adherent population. METHODS: In total,
      1859 participants aged 51-59 years (except those aged 55 years) were recruited
      from a Japanese urban community setting. Participants were randomly assigned to
      receive either a tailored print reminder (tailored intervention group) or non
      tailored print reminder (non-tailored intervention group). The primary outcome
      was improvement in the breast cancer screening rate. The screening rates and cost
      effectiveness were examined for each treatment group (tailored vs. non-tailored)
      and each intervention subgroup during a follow-up period of five months. All
      analyses followed the intention-to-treat principle. RESULTS: The number of women
      who underwent a screening mammogram following the reminder was 277 (19.9%) in the
      tailored reminder group and 27 (5.8%) in the non-tailored reminder group. A
      logistic regression model revealed that the odds of a woman who received a
      tailored print reminder undergoing mammography was 4.02 times those of a women
      who had received a non-tailored print reminder (95% confidence interval, 2.67
      6.06). The cost of one mammography screening increase was 2,544 JPY or 30 USD in
      the tailored intervention group and 4,366 JPY or 52 USD in the non-tailored
      intervention group. CONCLUSIONS: Providing a tailored print reminder was an
      effective and cost-effective strategy for improving breast cancer screening rates
      among non-adherent women.

PMID- 22962859
TI  - How to dress as a paediatrician?
AB  - AIM: Do different clothing styles have an influence on the doctor-patient-parent
      relationship and which kind of outfit is preferred by children and parents.
      METHODS: One hundred and seven children and 72 parents were visited by a
      paediatrician randomly wearing one of the three different outfits (casual,
      semiformal, formal) during a hospital stay. Parents and children between 6 and 18
      years were then interviewed about their opinion by use of a semi-structured
      questionnaire, while children between 0 and 6 years were observed concerning
      their behaviour during the examination. RESULTS: Using a 'likert scale', the
      casual outfit received the best mark by 95.5% of parents (58.3% in the
      semiformal, 30.8% in the formal group). The degree of the parents' trust in the
      paediatrician was comparable in all three groups. In children between 6 and 18
      years, the casual dress was rated highest in 100%. In children between 0 and 6
      years, the outfit had no significant influence on the patients' behaviour.
      CONCLUSION: Apparently, parents do not only tolerate a casual outfit, but even
      prefer it without any loss of trust. The same holds true for children between 6
      and 18 years. For younger children, the paediatricians' outfit seems to play no
      major role.

PMID- 22962860
TI  - Integrative analysis of chromatin states in Arabidopsis identified potential
      regulatory mechanisms for natural antisense transcript production.
AB  - Genome-wide analyses of epigenomic and transcriptomic profiles provide extensive
      resources for discovering epigenetic regulatory mechanisms. However, the
      construction of functionally relevant hypotheses from correlative patterns and
      the rigorous testing of these hypotheses may be challenging. We combined
      bioinformatics-driven hypothesis building with mutant analyses to identify
      potential epigenetic mechanisms using the model plant Arabidopsis thaliana.
      Genome-wide maps of nine histone modifications produced by ChIP-seq were used
      together with a strand-specific RNA-seq dataset to profile the epigenome and
      transcriptome of Arabidopsis. Combinatorial chromatin patterns were described by
      42 major chromatin states with selected states validated using the re-ChIP assay.
      The functional relevance of chromatin modifications was analyzed using the
      ANchored CORrelative Pattern (ANCORP) method and a newly developed state-specific
      effects analysis (SSEA) method, which interrogates individual chromatin marks in
      the context of combinatorial chromatin states. Based on results from these
      approaches, we propose the hypothesis that cytosine methylation (5mC) and histone
      methylation H3K36me may synergistically repress production of natural antisense
      transcripts (NATs) in the context of actively expressed genes. Mutant analyses
      supported this proposed model at a significant proportion of the tested loci. We
      further identified polymerase-associated factor as a potential repressor for NAT
      abundance. Although the majority of tested NATs were found to localize to the
      nucleus, we also found evidence for cytoplasmically partitioned NATs. The
      significance of the subcellular localization of NATs and their biological
      functions remain to be defined. 

PMID- 22962861
TI  - Clinical course of occupational irritant contact dermatitis of the hands in
      relation to filaggrin genotype status and atopy.
AB  - BACKGROUND: Filaggrin loss-of-function mutations and atopy may alter the clinical
      course of irritant contact dermatitis (ICD). OBJECTIVE: To investigate the
      clinical course of patients with occupational ICD according to loss-of-function
      mutations in the filaggrin gene (FLG) and atopy. METHODS: In a prospective cohort
      study, the clinical course, use of topical corticosteroids, sick leave, recovery
      rate and job continuation were investigated in 459 inpatients treated for
      occupational ICD of the hands. Patients were genotyped for four FLG mutations,
      examined for atopy and followed for up to 3 years after discharge. RESULTS: Our
      study included 327 (71.2%) atopic individuals and 132 nonatopic individuals.
      Overall, 68 patients showed a mutation in the FLG alleles R501X, R2447X, S3247X
      and 2282del4 (60 atopic and eight nonatopic). Nonatopic patients with ICD
      responded well to therapeutic approaches, while atopy status made subjects more
      resistant to therapy, resulting in lower rates of recovery and job continuation
      and higher use of topical corticosteroids. Carriage of FLG loss-of-function
      mutations in combination with atopy worsened the course. The risk of abandoning
      one's profession in this group was significantly increased when compared with
      'pure' ICD (odds ratio 3.1) after 3 years. CONCLUSIONS: Patients with atopy are a
      special risk population for ICD. In the presence of atopy, FLG mutations seem to
      be a modifier of the severity of the clinical course in ICD. Early-stage
      identification of this subgroup may result in additional emphasis to these
      patients regarding the importance of adherence to specific therapeutic
      interventions.

PMID- 22962862
TI  - Drug rash induced by levothyroxine tablets.

PMID- 22962863
TI  - The effect of a comprehensive lifestyle intervention on cardiovascular risk
      factors in pharmacologically treated patients with stable cardiovascular disease
      compared to usual care: a randomised controlled trial.
AB  - BACKGROUND: The additional benefit of lifestyle interventions in patients
      receiving cardioprotective drug treatment to improve cardiovascular risk profile
      is not fully established.The objective was to evaluate the effectiveness of a
      target-driven multidisciplinary structured lifestyle intervention programme of 6
      months duration aimed at maximum reduction of cardiovascular risk factors in
      patients with cardiovascular disease (CVD) compared with usual care. METHODS: A
      single centre, two arm, parallel group randomised controlled trial was performed.
      Patients with stable established CVD and at least one lifestyle-related risk
      factor were recruited from the vascular and cardiology outpatient departments of
      the university hospital. Blocked randomisation was used to allocate patients to
      the intervention (n = 71) or control group (n = 75) using an on-site computer
      system combined with allocations in computer-generated tables of random numbers
      kept in a locked computer file. The intervention group received the comprehensive
      lifestyle intervention offered in a specialised outpatient clinic in addition to
      usual care. The control group continued to receive usual care. Outcome measures
      were the lifestyle-related cardiovascular risk factors: smoking, physical
      activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL
      cholesterol concentrations, BMI, waist circumference, and changes in medication.
      RESULTS: The intervention led to increased physical activity/fitness levels and
      an improved cardiovascular risk factor profile (reduced BMI and waist
      circumference). In this setting, cardiovascular risk management for blood
      pressure and lipid levels by prophylactic treatment for CVD in usual care was
      already close to optimal as reflected in baseline levels. There was no
      significant improvement in any other risk factor. CONCLUSIONS: Even in CVD
      patients receiving good clinical care and using cardioprotective drug treatment,
      a comprehensive lifestyle intervention had a beneficial effect on some
      cardiovascular risk factors. In the present era of cardiovascular therapy and
      with the increasing numbers of overweight and physically inactive patients, this
      study confirms the importance of risk factor control through lifestyle
      modification as a supplement to more intensified drug treatment in patients with
      CVD. TRIAL REGISTRATION: ISRCTN69776211 at http://www.controlled-trials.com.

PMID- 22962864
TI  - The solution structure of the prototype foamy virus RNase H domain indicates an
      important role of the basic loop in substrate binding.
AB  - BACKGROUND: The ribonuclease H (RNase H) domains of retroviral reverse
      transcriptases play an essential role in the replication cycle of retroviruses.
      During reverse transcription of the viral genomic RNA, an RNA/DNA hybrid is
      created whose RNA strand needs to be hydrolyzed by the RNase H to enable
      synthesis of the second DNA strand by the DNA polymerase function of the reverse
      transcriptase. Here, we report the solution structure of the separately purified
      RNase H domain from prototype foamy virus (PFV) revealing the so-called C-helix
      and the adjacent basic loop, which both were suggested to be important in
      substrate binding and activity. RESULTS: The solution structure of PFV RNase H
      shows that it contains a mixed five-stranded beta-sheet, which is sandwiched by
      four alpha-helices (A-D), including the C-helix, on one side and one alpha-helix
      (helix E) on the opposite side. NMR titration experiments demonstrate that upon
      substrate addition signal changes can be detected predominantly in the basic loop
      as well as in the C-helix. All these regions are oriented towards the bound
      substrate. In addition, signal intensities corresponding to residues in the B
      helix and the active site decrease, while only minor or no changes of the overall
      structure of the RNase H are detectable upon substrate binding. Dynamic studies
      confirm the monomeric state of the RNase H domain. Structure comparisons with HIV
      1 RNase H, which lacks the basic protrusion, indicate that the basic loop is
      relevant for substrate interaction, while the C-helix appears to fulfill mainly
      structural functions, i.e. positioning the basic loop in the correct orientation
      for substrate binding. CONCLUSIONS: The structural data of PFV RNase H
      demonstrate the importance of the basic loop, which contains four positively
      charged lysines, in substrate binding and the function of the C-helix in
      positioning of the loop. In the dimeric full length HIV-1 RT, the function of the
      basic loop is carried out by a different loop, which also harbors basic residues,
      derived from the connection domain of the p66 subunit. Our results suggest that
      RNases H which are also active as separate domains might need a functional basic
      loop for proper substrate binding.

PMID- 22962865
TI  - Short-term intra-nasal erythropoietin administration with low sialic acid content
      is without toxicity or erythropoietic effects.
AB  - The objective of this investigation was to assess the toxicological potential of
      nasal formulation of erythropoietin with low sialic acid content (Neuro EPO)
      after 28 days of intra-nasal dosing in rats besides to evaluate the
      immunogenicity and erythropoietic effect of the test substance. Healthy Wistar
      rats of both sexes were used for 28 days subacute toxicity and immunogenicity
      assays. Doses evaluated were 3450, 4830 and 6900 UI/kg/day. The toxicological
      endpoints examined included animal body weight, food consumption, hematological
      and biochemical patterns, antibodies determination, selected tissue weights and
      histopathological examination. Reversibility of toxic effects was evaluated at
      high dose 14 days after treatment period. Female B6D2F1 mice were used for
      evaluated erythropoietic effect of the nasal formulation. Hematological endpoints
      were examined every week during 28 days of intra-nasal dosing of 6900 UI/kg/day.
      Variations of hematological patterns were not observed after 28 days of
      intranasal dosing. A slight increase in glucose level of treated animals within
      the normal range was observed. This effect was not dose related and was
      reversible. Antibody formation was not observed in any of the test doses.
      Histopathological examination of organs and tissues did not reveal treatment
      induced changes. The administration of Neuro EPO in normocythaemic mice did not
      produce erythropoietic effect. These results suggest that Neuro EPO could be used
      as a neuroprotective agent, without significant systemic haematological side
      effects.

PMID- 22962866
TI  - A walking stick can be a good alternative to a cane.

PMID- 22962867
TI  - Vitamin C for preventing exercise-induced asthma.

PMID- 22962868
TI  - Case study: Risks associated with congenital varicella infection.

PMID- 22962872
TI  - The door to recovery: overcoming drug and alcohol addiction.

PMID- 22962873
TI  - BPA exposure and health effects: educating physicians and patients.

PMID- 22962874
TI  - Risk stratification of patients presenting with syncope.

PMID- 22962875
TI  - Antiemetics for acute gastroenteritis-related vomiting in children and
      adolescents.

PMID- 22962876
TI  - Could selenium supplementation prevent cancer?

PMID- 22962877
TI  - Gastroenteritis in children: Part 1. Diagnosis.
AB  - Acute gastroenteritis in children is a major cause of morbidity in the United
      States. Viral infections, primarily from rotavirus, cause 75 to 90 percent of
      cases. The remaining infections are largely bacterial, with as many as 10 percent
      of cases secondary to diarrheagenic Escherichia coli. The history and physical
      examination of children with gastroenteritis should focus on assessing for the
      presence and degree of dehydration and determining the underlying etiology. The
      child's weight during the illness versus posttreatment is often used to evaluate
      degree of dehydration retrospectively. The three examination signs that best
      suggest dehydration in children are an abnormal respiratory pattern, abnormal
      skin turgor, and prolonged capillary refill time, although parental report of the
      child's history is also helpful in the assessment. In general, measuring serum
      electrolyte levels usually is unnecessary in children with mild to moderate
      dehydration. Laboratory tests are recommended only when severe dehydration is
      suspected; in such cases, intravenous fluids would be warranted. Although it is
      not necessary to routinely obtain stool cultures, they should be collected if
      diarrhea is persistent.

PMID- 22962878
TI  - Gastroenteritis in children: Part II. Prevention and management.
AB  - The treatment of gastroenteritis in children focuses on preventing dehydration. A
      child with minimal or no dehydration should be encouraged to continue his or her
      usual diet plus drink adequate fluids. Many studies have shown that a child's
      regular diet reduces the duration of diarrhea. Oral rehydration therapy with a
      rehydration solution can be used to treat diarrhea in children with mild to
      moderate dehydration. Ondansetron can decrease vomiting or help avoid the need
      for intravenous fluid, but it increases episodes of diarrhea. Probiotics can be
      used to shorten the course of diarrhea. Good handwashing reduces the incidence of
      acute gastroenteritis, but not rotavirus. The introduction of two rotavirus
      vaccines in the United States in 2006 significantly reduced the incidence of
      rotavirus gastroenteritis. The oral, live vaccines have strong safety records,
      despite a minimal incidence of intussusception.

PMID- 22962879
TI  - Evaluation and management of galactorrhea.
AB  - Galactorrhea is commonly caused by hyperprolactinemia, especially when it is
      associated with amenorrhea. Hyperprolactinemia is most often induced by
      medication or associated with pituitary adenomas or other sellar or suprasellar
      lesions. Less common causes of galactorrhea include hypothyroidism, renal
      insufficiency, pregnancy, and nipple stimulation. After pathologic nipple
      discharge is ruled out, patients with galactorrhea should be evaluated by
      measurement of their prolactin level. Those with hyperprolactinemia should have
      pregnancy ruled out, and thyroid and renal function assessed. Brain magnetic
      resonance imaging should be performed if no other cause of hyperprolactinemia is
      found. Patients with prolactinomas are usually treated with dopamine agonists
      (bromocriptine or cabergoline); surgery or radiation therapy is rarely required.
      Medications causing hyperprolactinemia should be discontinued or replaced with a
      medication from a similar class with lower potential for causing
      hyperprolactinemia. Normoprolactinemic patients with idiopathic, nonbothersome
      galactorrhea can be reassured and do not need treatment; however, those with
      bothersome galactorrhea usually respond to a short course of a low-dose dopamine
      agonist.

PMID- 22962880
TI  - Diagnosis and management of Lyme disease.
AB  - Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common
      tick-borne illness in the United States. Transmission occurs primarily through
      the bite of an infected deer tick (Ixodes scapularis). Identification of an
      erythema migrans rash following a tick bite is the only clinical manifestation
      sufficient to make the diagnosis of Lyme disease in the absence of laboratory
      confirmation. The Centers for Disease Control and Prevention recommends a two
      tier serologic testing protocol using an enzyme-linked immunosorbent assay
      initially, followed by the more specific Western blot to confirm the diagnosis
      when the assay samples are positive or equivocal. The treatment of Lyme disease
      is determined mainly by the clinical manifestations of the disease. Doxycycline
      is often the preferred agent for oral treatment because of its activity against
      other tick-borne illnesses. Preventive measures include avoiding areas with high
      tick burdens, wearing protective clothing, using tick repellants (e.g.,
      diethyltoluamide [DEET]), performing frequent body checks and bathing following
      outdoor activities, and instituting environmental landscape modifications (e.g.,
      grass mowing, deer exclusion fencing) to reduce the tick burden. Although there
      is controversy regarding treatment of post-Lyme disease syndrome and chronic Lyme
      disease, there is no biologic or clinical trial evidence indicating that
      prolonged antibiotic therapy is of benefit.

PMID- 22962881
TI  - Cystic lesion near the lateral lower eyelid. Hydrocystoma.

PMID- 22962883
TI  - Galactorrhea (milk discharge).

PMID- 22962884
TI  - Gastroenteritis in children: treating dehydration.

PMID- 22962885
TI  - Lyme disease.

PMID- 22962886
TI  - Bayesian structural equation modeling: a more flexible representation of
      substantive theory.
AB  - This article proposes a new approach to factor analysis and structural equation
      modeling using Bayesian analysis. The new approach replaces parameter
      specifications of exact zeros with approximate zeros based on informative, small
      variance priors. It is argued that this produces an analysis that better reflects
      substantive theories. The proposed Bayesian approach is particularly beneficial
      in applications where parameters are added to a conventional model such that a
      nonidentified model is obtained if maximum-likelihood estimation is applied. This
      approach is useful for measurement aspects of latent variable modeling, such as
      with confirmatory factor analysis, and the measurement part of structural
      equation modeling. Two application areas are studied, cross-loadings and residual
      correlations in confirmatory factor analysis. An example using a full structural
      equation model is also presented, showing an efficient way to find model
      misspecification. The approach encompasses 3 elements: model testing using
      posterior predictive checking, model estimation, and model modification. Monte
      Carlo simulations and real data are analyzed using Mplus. The real-data analyses
      use data from Holzinger and Swineford's (1939) classic mental abilities study,
      Big Five personality factor data from a British survey, and science achievement
      data from the National Educational Longitudinal Study of 1988.

PMID- 22962887
TI  - Next steps in Bayesian structural equation models: comments on, variations of,
      and extensions to Muthen and Asparouhov (2012).
AB  - Muthen and Asparouhov (2012) made a strong case for the advantages of Bayesian
      methodology in factor analysis and structural equation models. I show additional
      extensions and adaptations of their methods and show how non-Bayesians can take
      advantage of many (though not all) of these advantages by using interval
      restrictions on parameters. By keeping parameters restricted to intervals (such
      as loadings between -.3 and .3 to produce small loadings), frequentists using
      standard structural equation modeling software can do something similar to what a
      Bayesian does by putting prior distributions on these parameters.

PMID- 22962888
TI  - Hopes and cautions in implementing Bayesian structural equation modeling.
AB  - Muthen and Asparouhov (2012) have proposed and demonstrated an approach to model
      specification and estimation in structural equation modeling (SEM) using Bayesian
      methods. Their contribution builds on previous work in this area by (a) focusing
      on the translation of conventional SEM models into a Bayesian framework wherein
      parameters fixed at zero in a conventional model can be respecified using small
      variance priors and (b) implementing their approach in software that is widely
      accessible. We recognize potential benefits for applied researchers as discussed
      by Muthen and Asparouhov, and we also see a tradeoff in that effective use of the
      proposed approach introduces increased demands in terms of expertise of users to
      navigate new complexities in model specification, parameter estimation, and
      evaluation of results. We also raise cautions regarding the issues of model
      modification and model fit. Although we see significant potential value in the
      use of Bayesian SEM, we also believe that effective use will require an awareness
      of these complexities.

PMID- 22962892
TI  - NSAIDs for relieving renal colic in patients with kidney stones.

PMID- 22962894
TI  - Bisphosphonate-related osteonecrosis of the jaw in patients with osteoporosis.

PMID- 22962895
TI  - Hearing loss in older adults.
AB  - Hearing loss affects approximately one-third of adults 61 to 70 years of age and
      more than 80 percent of those older than 85 years. Men usually experience greater
      hearing loss and have earlier onset compared with women. The most common type is
      age-related hearing loss; however, many conditions can interfere with the
      conduction of sound vibrations to the inner ear and their conversion to
      electrical impulses for conduction to the brain. Screening for hearing loss is
      recommended in adults older than 50 to 60 years. Office screening tests include
      the whispered voice test and audioscopy. Older patients who admit to having
      difficulty hearing may be referred directly for audiometry. The history can
      identify risk factors for hearing loss, especially noise exposure and use of
      ototoxic medications. Examination of the auditory canal and tympanic membrane can
      identify causes of conductive hearing loss. Audiometric testing is required to
      confirm hearing loss. Adults presenting with idiopathic sudden sensorineural
      hearing loss should be referred for urgent assessment. Management of hearing loss
      is based on addressing underlying causes, especially obstructions (including
      cerumen) and ototoxic medications. Residual hearing should be optimized by use of
      hearing aids, assistive listening devices, and rehabilitation programs. Surgical
      implants are indicated for selected patients. Major barriers to improved hearing
      in older adults include lack of recognition of hearing loss; perception that
      hearing loss is a normal part of aging or is not amenable to treatment; and
      patient nonadherence with hearing aids because of stigma, cost, inconvenience,
      disappointing initial results, or other factors.

PMID- 22962896
TI  - Diagnosis and evaluation of heart failure.
AB  - Heart failure is a common clinical syndrome characterized by dyspnea, fatigue,
      and signs of volume overload, which may include peripheral edema and pulmonary
      rales. Heart failure has high morbidity and mortality rates, especially in older
      persons. Many conditions, such as coronary artery disease, hypertension, valvular
      heart disease, and diabetes mellitus, can cause or lead to decompensation of
      chronic heart failure. Up to 40 to 50 percent of patients with heart failure have
      diastolic heart failure with preserved left ventricular function, and the overall
      mortality is similar to that of systolic heart failure. The initial evaluation
      includes a history and physical examination, chest radiography,
      electrocardiography, and laboratory assessment to identify causes or
      precipitating factors. A displaced cardiac apex, a third heart sound, and chest
      radiography findings of venous congestion or interstitial edema are useful in
      identifying heart failure. Systolic heart failure is unlikely when the Framingham
      criteria are not met or when B-type natriuretic peptide level is normal.
      Echocardiography is the diagnostic standard to confirm systolic or diastolic
      heart failure through assessment of left ventricular ejection fraction.
      Evaluation for ischemic heart disease is warranted in patients with heart
      failure, especially if angina is present, given that coronary artery disease is
      the most common cause of heart failure.

PMID- 22962897
TI  - Update on acute ankle sprains.
AB  - Ankle sprains are a common problem seen by primary care physicians, especially
      among teenagers and young adults. Most ankle sprains are inversion injuries to
      the lateral ankle ligaments, although high sprains representing damage to the
      tibiofibular syndesmosis are becoming increasingly recognized. Physicians should
      apply the Ottawa ankle rules to determine whether radiography is needed.
      According to the Ottawa criteria, radiography is indicated if there is pain in
      the malleolar or midfoot zone, and either bone tenderness over an area of
      potential fracture (i.e., lateral malleolus, medial malleolus, base of fifth
      metatarsal, or navicular bone) or an inability to bear weight for four steps
      immediately after the injury and in the emergency department or physician's
      office. Patients with ankle sprain should use cryotherapy for the first three to
      seven days to reduce pain and improve recovery time. Patients should wear a lace
      up ankle support or an air stirrup brace combined with an elastic compression
      wrap to reduce swelling and pain, speed recovery, and protect the injured
      ligaments as they become more mobile. Early mobilization speeds healing and
      reduces pain more effectively than prolonged rest. Pain control options for
      patients with ankle sprain include nonsteroidal anti-inflammatory drugs,
      acetaminophen, and mild opioids. Because a previous ankle sprain is the greatest
      risk factor for an acute ankle sprain, recovering patients should be counseled on
      prevention strategies. Ankle braces and supports, ankle taping, a focused
      neuromuscular training program, and regular sport-specific warm-up exercises can
      protect against ankle injuries, and should be considered for patients returning
      to sports or other high-risk activities.

PMID- 22962898
TI  - Transient ischemic attack: the rules have changed.

PMID- 22962900
TI  - Enlarging, pedunculated skin lesion. Acrochordon.

PMID- 22962903
TI  - Information from your family doctor. How to care for your ankle sprain.

PMID- 22962904
TI  - FPIN's clinical inquiries. Advantages of the no-scalpel vasectomy technique.

PMID- 22962906
TI  - Cover illustration should have emphasized cough hygiene.

PMID- 22962908
TI  - School-based management of food allergies in children.

PMID- 22962909
TI  - Adding ACE inhibitors or ARBs to standard therapy for stable ischemic heart
      disease.

PMID- 22962910
TI  - Interventions to prevent childhood obesity.

PMID- 22962911
TI  - Atopic dermatitis: an overview.
AB  - Atopic dermatitis, also known as atopic eczema, is a chronic pruritic skin
      condition affecting approximately 17.8 million persons in the United States. It
      can lead to significant morbidity. A simplified version of the U.K. Working
      Party's Diagnostic Criteria can help make the diagnosis. Asking about the
      presence and frequency of symptoms can allow physicians to grade the severity of
      the disease and response to treatment. Management consists of relieving symptoms
      and lengthening time between flare-ups. Regular, liberal use of emollients is
      recommended. The primary pharmacologic treatment is topical corticosteroids.
      Twice-daily or more frequent application has not been shown to be more effective
      than once-daily application. A maintenance regimen of topical corticosteroids may
      reduce relapse rates in patients who have recurrent moderate to severe atopic
      dermatitis. Pimecrolimus and tacrolimus are calcineurin inhibitors that are
      recommended as second-line treatment for persons with moderate to severe atopic
      dermatitis and who are at risk of atrophy from topical corticosteroids. Although
      the U.S. Food and Drug Administration has issued a boxed warning about a possible
      link between these medications and skin malignancies and lymphoma, studies have
      not demonstrated a clear link. Topical and oral antibiotics may be used to treat
      secondary bacterial infections, but are not effective in preventing atopic
      dermatitis flare-ups. The effectiveness of alternative therapies, such as Chinese
      herbal preparations, homeopathy, hypnotherapy/biofeedback, and massage therapy,
      has not been established.

PMID- 22962912
TI  - Summary of the NIAID-sponsored food allergy guidelines.
AB  - Patients with suspected food allergies are commonly seen in clinical practice.
      Although up to 15 percent of parents believe their children have food allergies,
      these allergies have been confirmed in only 1 to 3 percent of all Americans.
      Family physicians must be able to separate true food allergies from food
      intolerance, food dislikes, and other conditions that mimic food allergy. The
      most common foods that produce allergic symptoms are milk, eggs, seafood,
      peanuts, and tree nuts. Although skin testing and in vitro serum immunoglobulin E
      assays may help in the evaluation of suspected food allergies, they should not be
      performed unless the clinical history suggests a specific food allergen to which
      testing can be targeted. Furthermore, these tests do not confirm food allergy.
      Confirmation requires a positive food challenge or a clear history of an allergic
      reaction to a food and resolution of symptoms after eliminating that food from
      the diet. More than 70 percent of children will outgrow milk and egg allergies by
      early adolescence, whereas peanut allergies usually remain throughout life. The
      most serious allergic response to food allergy is anaphylaxis. It requires
      emergency care that should be initiated by the patient or family using an
      epinephrine autoinjector, which should be carried by anyone with a diagnosed food
      allergy. These and other recommendations presented in this article are derived
      from the Guidelines for the Diagnosis and Management of Food Allergy in the
      United States, published by the National Institute of Allergy and Infectious
      Diseases.

PMID- 22962913
TI  - Prevention of perinatal group B streptococcal disease: updated CDC guideline.
AB  - Group B streptococcus is the leading cause of early-onset neonatal sepsis in the
      United States. Universal screening is recommended for pregnant women at 35 to 37
      weeks' gestation. The Centers for Disease Control and Prevention recently updated
      its guideline for the prevention of early-onset neonatal group B streptococcal
      disease. The new guideline contains six important changes. First, there is a
      recommendation to consider using sensitive nucleic acid amplification tests,
      rather than just routine cultures, for detection of group B streptococcus in
      rectal and vaginal specimens. Second, the colony count required to consider a
      urine specimen positive is at least 104 colony-forming units per mL. Third, the
      new guideline presents separate algorithms for management of preterm labor and
      preterm premature rupture of membranes, rather than a single algorithm for both
      conditions. Fourth, there are minor changes in the recommended dose of penicillin
      G for intrapartum chemoprophylaxis. Fifth, the guideline provides new
      recommendations about antibiotic regimens for women with penicillin allergy.
      Cefazolin is recommended for women with minor allergies. For those at serious
      risk of anaphylaxis, clindamycin is recommended if the organism is susceptible
      [corrected] and vancomycin is recommended if there is clindamycin resistance or
      if susceptibility is unknown. [corrected]. Finally, the new algorithm for
      secondary prevention of early-onset group B streptococcal disease in newborns
      should be applied to all infants, not only those at high risk of infection. The
      algorithm clarifies the extent of evaluation and duration of observation required
      for infants in different risk categories.

PMID- 22962914
TI  - Reducing adverse effects of proton pump inhibitors.
AB  - Proton pump inhibitors effectively treat gastroesophageal reflux disease, erosive
      esophagitis, duodenal ulcers, and pathologic hypersecretory conditions. Proton
      pump inhibitors cause few adverse effects with short-term use; however, long-term
      use has been scrutinized for appropriateness, drug-drug interactions, and the
      potential for adverse effects (e.g., hip fractures, cardiac events, iron
      deficiency, Clostridium difficile infection, pneumonia). Adults 65 years and
      older are more vulnerable to these adverse effects because of the higher
      prevalence of chronic diseases in this population. Proton pump inhibitors
      administered for stress ulcer prophylaxis should be discontinued after the
      patient is discharged from the intensive care unit unless other indications
      exist.

PMID- 22962915
TI  - Evaluating and treating sexual addiction.

PMID- 22962916
TI  - Painless, red nodule on the finger of a veterinary student.

PMID- 22962918
TI  - Side effects of proton pump inhibitors.

PMID- 22962919
TI  - Eczema.

PMID- 22962920
TI  - Food allergies.

PMID- 22962921
TI  - GBS testing during pregnancy.

PMID- 22962922
TI  - Dementia has a categorical, not dimensional, latent structure.
AB  - Recently, Walters ("Dementia: Continuum or distinct entity?", Psychology and
      Aging, 2010, 25, 534-544) published a taxometric study suggesting a dimensional
      latent structure for the construct of dementia. However, because that study did
      not conceptualize dementia according to accepted conventions (i.e., there were no
      measures of cognitive change or independent functioning), its results may
      represent a false negative error caused by insufficient content coverage. We
      replicated Walters, and we used the same taxometric methods and the same data
      source--but with indicators of cognitive change and functional independence. Our
      results support a categorical interpretation of dementia; whereas Walters'
      results suggest that cognitive ability, rather than dementia, is dimensional in
      nature.

PMID- 22962925
TI  - Choosing wisely: top interventions to improve health and reduce harm, while
      lowering costs.

PMID- 22962926
TI  - The "ARB-MI paradox": real or a fluke?

PMID- 22962927
TI  - Treatment of the common cold in children and adults.
AB  - The common cold, or upper respiratory tract infection, is one of the leading
      reasons for physician visits. Generally caused by viruses, the common cold is
      treated symptomatically. Antibiotics are not effective in children or adults. In
      children, there is a potential for harm and no benefits with over-the-counter
      cough and cold medications; therefore, they should not be used in children
      younger than four years. Other commonly used medications, such as inhaled
      corticosteroids, oral prednisolone, and Echinacea, also are ineffective in
      children. Products that improve symptoms in children include vapor rub, zinc
      sulfate, Pelargonium sidoides (geranium) extract, and buckwheat honey.
      Prophylactic probiotics, zinc sulfate, nasal saline irrigation, and the herbal
      preparation Chizukit reduce the incidence of colds in children. For adults,
      antihistamines, intranasal corticosteroids, codeine, nasal saline irrigation,
      Echinacea angustifolia preparations, and steam inhalation are ineffective at
      relieving cold symptoms. Pseudoephedrine, phenylephrine, inhaled ipratropium, and
      zinc (acetate or gluconate) modestly reduce the severity and duration of symptoms
      for adults. Nonsteroidal anti-inflammatory drugs and some herbal preparations,
      including Echinacea purpurea, improve symptoms in adults. Prophylactic use of
      garlic may decrease the frequency of colds in adults, but has no effect on
      duration of symptoms. Hand hygiene reduces the spread of viruses that cause cold
      illnesses. Prophylactic vitamin C modestly reduces cold symptom duration in
      adults and children.

PMID- 22962928
TI  - Diagnosis and treatment of Basal cell and squamous cell carcinoma.
AB  - Family physicians are regularly faced with identifying, treating, and counseling
      patients with skin cancers. Nonmelanoma skin cancer, which encompasses basal cell
      and squamous cell carcinoma, is the most common cancer in the United States.
      Ultraviolet B exposure is a significant factor in the development of basal cell
      and squamous cell carcinoma. The use of tanning beds is associated with a 1.5
      fold increase in the risk of basal cell carcinoma and a 2.5-fold increase in the
      risk of squamous cell carcinoma. Routine screening for skin cancer is
      controversial. The U.S. Preventive Services Task Force cites insufficient
      evidence to recommend for or against routine whole-body skin examination to
      screen for skin cancer. Basal cell carcinoma most commonly appears as a pearly
      white, dome-shaped papule with prominent telangiectatic surface vessels. Squamous
      cell carcinoma most commonly appears as a firm, smooth, or hyperkeratotic papule
      or plaque, often with central ulceration. Initial tissue sampling for diagnosis
      involves a shave technique if the lesion is raised, or a 2- to 4-mm punch biopsy
      of the most abnormal-appearing area of skin. Mohs micrographic surgery has the
      lowest recurrence rate among treatments, but is best considered for large, high
      risk tumors. Smaller, lower-risk tumors may be treated with surgical excision,
      electrodesiccation and curettage, or cryotherapy. Topical imiquimod and
      fluorouracil are also potential, but less supported, treatments. Although there
      are no clear guidelines for follow-up after an index nonmelanoma skin cancer,
      monitoring for recurrence is prudent because the risk of subsequent skin cancer
      is 35 percent at three years and 50 percent at five years.

PMID- 22962929
TI  - Causes and evaluation of chronic dyspnea.
AB  - Chronic dyspnea is shortness of breath that lasts more than one month. The
      perception of dyspnea varies based on behavioral and physiologic responses.
      Dyspnea that is greater than expected with the degree of exertion is a symptom of
      disease. Most cases of dyspnea result from asthma, heart failure and myocardial
      ischemia, chronic obstructive pulmonary disease, interstitial lung disease,
      pneumonia, or psychogenic disorders. The etiology of dyspnea is multifactorial in
      about one-third of patients. The clinical presentation alone is adequate to make
      a diagnosis in 66 percent of patients with dyspnea. Patients' descriptions of the
      sensation of dyspnea may be helpful, but associated symptoms and risk factors,
      such as smoking, chemical exposures, and medication use, should also be
      considered. Examination findings (e.g., jugular venous distention, decreased
      breath sounds or wheezing, pleural rub, clubbing) may be helpful in making the
      diagnosis. Initial testing in patients with chronic dyspnea includes chest
      radiography, electrocardiography, spirometry, complete blood count, and basic
      metabolic panel. Measurement of brain natriuretic peptide levels may help exclude
      heart failure, and D-dimer testing may help rule out pulmonary emboli. Pulmonary
      function studies can be used to identify emphysema and interstitial lung
      diseases. Computed tomography of the chest is the most appropriate imaging study
      for diagnosing suspected pulmonary causes of chronic dyspnea. To diagnose
      pulmonary arterial hypertension or certain interstitial lung diseases, right
      heart catheterization or bronchoscopy may be needed.

PMID- 22962931
TI  - Gastric ulcer and abnormal findings on CT.

PMID- 22962932
TI  - FPIN's Clinical Inquiries. Treatment of motion sickness.

PMID- 22962933
TI  - PIDS and IDSA issue management guidelines for community-acquired pneumonia in
      infants and young children.

PMID- 22962934
TI  - Information from your family doctor. Skin cancer: basal cell and squamous cell
      carcinoma.

PMID- 22962935
TI  - Information from your family doctor. Treating the common cold in children.

PMID- 22962936
TI  - Information from your family doctor. Treating the common cold in adults.

PMID- 22962937
TI  - Distinguishing late-onset stress symptomatology from posttraumatic stress
      disorder in older combat veterans.
AB  - OBJECTIVE: To assess the discriminant validity of late-onset stress
      symptomatology (LOSS) in terms of its distinction from posttraumatic stress
      disorder (PTSD). METHOD: The LOSS Scale, PTSD Checklist - Civilian Version, and
      related psychological measures were administered to 562 older male combat
      veterans via a mailed questionnaire. Analyses focused on: (a) comparing
      associations of LOSS and PTSD with other psychological variables and (b)
      examining a hypothesized curvilinear relationship between LOSS and PTSD scores.
      RESULTS: Compared to PTSD, LOSS was more strongly associated with concerns about
      retirement and less strongly associated with depression, anxiety, sense of
      mastery, and satisfaction with life. LOSS also demonstrated a curvilinear
      relationship with PTSD, such that the positive association between LOSS and PTSD
      diminished at higher levels of PTSD. CONCLUSION: LOSS is conceptually and
      statistically more strongly associated with a normative late-life stressor than
      is PTSD, but is less strongly related to mental health symptoms and emotional
      well-being. Additionally, LOSS seems more related to subthreshold PTSD than it is
      to clinically significant PTSD. The present findings support the discriminant
      validity of LOSS.

PMID- 22962938
TI  - Evidence-based docking of the urease activation complex.
AB  - Ureases require accessory proteins for their activation and proper function. In
      Klebsiella aerogenes, UreD, UreF, UreG, and UreE are sequentially complexed to
      UreABC as required for its activation. Until now, only low-resolution structures
      are available for this activation complex. To circumvent such limitation, our
      work intends to provide an atomic-level model for the (UreABC-UreDFG)3 complex
      from K. aerogenes, by employing comparative modeling associated to sequential
      macromolecular dockings, validated through small-angle X-ray scattering profiles
      and comparison with results from cross-linking, mutagenesis, and pull-down
      experiments. Additionally, normal mode analyses of the obtained complex supported
      the characterization of the elevated flexibility of both UreD-UreF dimer and
      (UreABC-UreDFG)3 oligomer, explaining the previously observed diffuse binding of
      UreD to the apoenzyme. The model shown here is the first atomic-level depiction
      of this complex, a required step for the unraveling of the urease activation
      process. (1)Both authors share senior authorship. An animated Interactive 3D
      Complement (I3DC) is available in Proteopedia at
      http://proteopedia.org/w/Journal:JBSD:6.

PMID- 22962939
TI  - Four botanical extracts are toxic to the hispine beetle, Brontispa longissima, in
      laboratory and semi-field trials.
AB  - The potential of botanical extracts such as Celosia argenea L. (Caryophyllales:
      Amaranthaceae), Ricinus communis L. (Malpighiales: Euphorbiaceae), Mikania
      micrantha Humboldt, Bonpland & Kunth (Astrales: Asteraceae), and Catharanthus
      roseus (L.) G. Don (Gentianales: Apocynaceae) for the control of Brontispa
      longissima Gestro was evaluated in a bioassay and semi-field trial. Dose-response
      bioassay showed no significant difference in oral-toxicity among the extracts of
      C. argenea, M. micrantha, and C. roseus to larvae and adult of B. longissima. All
      extracts tested decreased the hatchability of B. longissima eggs. In particular,
      the extract of M. micrantha showed higher activity than others at the
      concentration of 5 mg/mL. In an antifeedant bioassay, the extract of C. argenea
      showed higher activity against the 1(st) larvae than that of other extracts (AF50
      0.03 mg/mL), and C. roseus showed higher antifeedant activity to the 2(nd) to
      5(th) larvae and adult of B. longissima (AF50 0.34, 0.33, 0.11, 0.43, and 0.20
      mg/mL, respectively). The semi-field trial indicated that all extracts used in
      this study might reduce the pest population. Extracts of C. argenea and M.
      micrantha showed higher activities than that of C. roseus and R communis, and the
      decrease in population was 75.56% and 80.00% (without Abbott's correction) after
      seven days of treatment, respectively, at a concentration of 20 mg/mL. Therefore,
      these active botanical extracts may possess potential for use in control of B.
      longissima.

PMID- 22962940
TI  - The impact of thyroid nodule size on the risk of malignancy and accuracy of fine
      needle aspiration: a 10-year study from a single institution.
AB  - BACKGROUND: False-negative rates for thyroid fine-needle aspiration (FNA) vary
      from 0.4% to 13%, but the effect of nodule size on the accuracy of thyroid FNA
      remains controversial. We hypothesized that large thyroid nodule size does not
      contribute to the risk of malignancy or the risk of a false-negative FNA.
      METHODS: All thyroid FNAs performed at the Walter Reed Army Medical Center during
      September 2001-August 2011 were reviewed. A strict correlation between the biopsy
      site, location, and size of nodule on ultrasound (US) and pathology report was
      ensured. FNA results were classified as benign, atypical, follicular
      neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy
      (SM), or malignant, and the pathology result was categorized as either benign or
      malignant. Nodules were analyzed by size: 0.5-0.9 cm (group A), 1.0-3.9 cm (group
      B), and >= 4 cm (group C). Incidental thyroid cancer was not included. RESULTS:
      Of 3013 patients undergoing FNA, 667 (22.1%) had surgery. Patients were excluded
      for nodules <0.5 cm, nondiagnostic FNA, or no preoperative US, leaving 540
      patients with 695 nodules. Among patients referred for surgery, FNA results were
      benign in 417 nodules (60%), atypical in 22 (3.2%), FN/SFN in 122 (17.6%), SM in
      77 (11.1%), and malignant in 57 (8.2%). Postoperative malignancy rates by FNA
      result were 7% if benign, 4.5% if atypical, 23% if FN/SFN, 33.8% if SM, and 78.9%
      if malignant. FNA accuracy was 60% in group A, 68.5% in group B, and 80.3% in
      group C (p=0.01). False-negative rates for FNA were 7.0% overall, 15.8% in group
      A, 6.3% in group B, and 7.1% in group C (p=0.25). Sensitivity and negative
      predictive value were highest in group B at 81.6% and 93.7%, respectively. The
      prevalence of malignancy was not different between groups. CONCLUSION: Our
      results show that the thyroid nodule size >= 4 cm increases neither the risk of
      false-negative FNA results, nor the overall risk of malignancy. We also show a
      tendency toward a higher false-negative rate in subcentimeter nodules. We
      conclude that a large nodule size should not prompt automatic referral for
      thyroidectomy. An increased awareness of potential sampling error in
      subcentimeter nodules is warranted.

PMID- 22962941
TI  - Association of coronary artery calcium score and vascular dysfunction in long
      term hemodialysis patients.
AB  - Long-term hemodialysis patients are prone to an exceptionally high burden of
      cardiovascular disease and mortality. The novel temperature-based technology of
      digital thermal monitoring (DTM) of vascular reactivity appears associated with
      the severity of coronary artery disease in asymptomatic population. We
      hypothesized that in hemodialysis patients, the DTM and coronary artery calcium
      (CAC) score have a gradient association that follows that of subjects without
      kidney disease. We examined the cross-sectional DTM-CAC associations in a group
      of long-term hemodialysis patients, and their 1:1 matched normal counterpart.
      Area under the curve for temperature (TMP-AUC), the surrogate of the DTM index of
      vascular function, was assessed after a 5-minute arm-cuff reactive hyperemia
      test. Coronary calcium score was measured via electron beam computed tomography
      or multidetector computed tomography scan. We studied 105 randomly recruited
      hemodialysis patients (age: 58 +/- 13 years, 47% men) and 105 age- and gender
      matched controls. In hemodialysis patients vs. controls, TMP-AUC was
      significantly worse (114 +/- 72 vs. 143 +/- 80, P = 0.001) and CAC score was
      higher (525 +/- 425 vs. 240 +/- 332, P < 0.001). Hemodialysis patients were 14
      times more likely to have CAC score >1000 as compared with controls. After
      adjustment for known confounders, the relative risk for case vs. control for each
      standard deviation decrease in TMP-AUC was 1.46 (95% confidence interval: 1.12
      1.93, P = 0.007). Vascular reactivity measured via the novel DTM technology is
      incrementally worse across CAC scores in hemodialysis patients, in whom both
      measures are even worse than their age- and gender-matched controls. The DTM
      technology may offer a convenient and radiation-free approach to risk-stratify
      hemodialysis patients.

PMID- 22962942
TI  - How does gender influence immigrant and refugee women's postpartum depression
      help-seeking experiences?
AB  - The number of migrants arriving in Canada from non-European countries has grown
      significantly over the past three decades. How best to assist these escalating
      numbers of immigrant and refugee women to adapt to their new environment and to
      cope with postpartum depression (PPD) is a pressing issue for healthcare
      providers. Evidence has shown that immigrant and refugee women experience
      difficulties in accessing care and treatment for PPD. This qualitative study was
      conducted with 30 immigrant and refugee women using in-depth interviews to obtain
      information about the women's PPD experiences. The primary aim was to explore how
      cultural, social, political, historical and economic factors intersect with race,
      gender and class to influence the ways in which immigrant and refugee women seek
      help to manage PPD. Results reveal that immigrant and refugee women experience
      many complex gender-related challenges and facilitators in seeking equitable help
      for PPD treatment and prevention. We will demonstrate that (a) structural
      barriers and gender roles hinder women's ability to access necessary mental
      healthcare services and (b) insecure immigration status coupled with emotional
      and economic dependence may leave women vulnerable and disadvantaged in
      protecting themselves against PPD.

PMID- 22962943
TI  - Increase of electronegative-LDL-fraction ratio and IDL-cholesterol in chronic
      kidney disease patients with hemodialysis treatment.
AB  - BACKGROUND: It is known that the increased level of IDL and oxidized LDL are
      associated with risk of cardiovascular disease, and the lipoprotein abnormalities
      accelerate atherosclerosis. Cardiovascular disease is a major cause of mortality
      in chronic kidney disease patients with hemodialysis treatment (HD-Ps).
      Therefore, the estimation of lipoprotein profiles is important for prevention of
      cardiovascular disease in HD-Ps. We previously established an anion-exchange
      chromatographic method for measurement of cholesterol level in subclasses of HDL
      and LDL, IDL, VLDL, and chylomicron. An electronegative-LDL-fraction contained
      minimally oxidized-LDL. Lipoprotein profile can be accurately and conveniently
      determined by the new method. FINDING: In this study, lipoprotein profiles in HD
      Ps and age-matched healthy subjects were estimated by using our established anion
      exchange chromatographic method. The ratio of electronegative-LDL-cholesterol to
      total LDL-cholesterol and IDL-cholesterol in HD-Ps were significant higher than
      those in healthy subjects. CONCLUSIONS: The results suggest that the ratio of
      electronegative-LDL-cholesterol to total LDL-cholesterol and IDL-cholesterol
      obtained by the new method may serve as useful markers for risk of cardiovascular
      disease in HD-Ps.

PMID- 22962944
TI  - Bayesian model selection techniques as decision support for shaping a statistical
      analysis plan of a clinical trial: an example from a vertigo phase III study with
      longitudinal count data as primary endpoint.
AB  - BACKGROUND: A statistical analysis plan (SAP) is a critical link between how a
      clinical trial is conducted and the clinical study report. To secure objective
      study results, regulatory bodies expect that the SAP will meet requirements in
      pre-specifying inferential analyses and other important statistical techniques.
      To write a good SAP for model-based sensitivity and ancillary analyses involves
      non-trivial decisions on and justification of many aspects of the chosen setting.
      In particular, trials with longitudinal count data as primary endpoints pose
      challenges for model choice and model validation. In the random effects setting,
      frequentist strategies for model assessment and model diagnosis are complex and
      not easily implemented and have several limitations. Therefore, it is of interest
      to explore Bayesian alternatives which provide the needed decision support to
      finalize a SAP. METHODS: We focus on generalized linear mixed models (GLMMs) for
      the analysis of longitudinal count data. A series of distributions with over- and
      under-dispersion is considered. Additionally, the structure of the variance
      components is modified. We perform a simulation study to investigate the
      discriminatory power of Bayesian tools for model criticism in different scenarios
      derived from the model setting. We apply the findings to the data from an open
      clinical trial on vertigo attacks. These data are seen as pilot data for an
      ongoing phase III trial. To fit GLMMs we use a novel Bayesian computational
      approach based on integrated nested Laplace approximations (INLAs). The INLA
      methodology enables the direct computation of leave-one-out predictive
      distributions. These distributions are crucial for Bayesian model assessment. We
      evaluate competing GLMMs for longitudinal count data according to the deviance
      information criterion (DIC) or probability integral transform (PIT), and by using
      proper scoring rules (e.g. the logarithmic score). RESULTS: The instruments under
      study provide excellent tools for preparing decisions within the SAP in a
      transparent way when structuring the primary analysis, sensitivity or ancillary
      analyses, and specific analyses for secondary endpoints. The mean logarithmic
      score and DIC discriminate well between different model scenarios. It becomes
      obvious that the naive choice of a conventional random effects Poisson model is
      often inappropriate for real-life count data. The findings are used to specify an
      appropriate mixed model employed in the sensitivity analyses of an ongoing phase
      III trial. CONCLUSIONS: The proposed Bayesian methods are not only appealing for
      inference but notably provide a sophisticated insight into different aspects of
      model performance, such as forecast verification or calibration checks, and can
      be applied within the model selection process. The mean of the logarithmic score
      is a robust tool for model ranking and is not sensitive to sample size.
      Therefore, these Bayesian model selection techniques offer helpful decision
      support for shaping sensitivity and ancillary analyses in a statistical analysis
      plan of a clinical trial with longitudinal count data as the primary endpoint.

PMID- 22962945
TI  - Effects of glutamine supplementation on the immune status in weaning piglets with
      intrauterine growth retardation.
AB  - Neonates with intrauterine growth retardation (IUGR) often suffer from impaired
      cellular immunity, and weaning may further aggravate adverse effects of IUGR on
      development and function of the immune system. In this study, we investigated
      effects of glutamine supplementation on immune status in the intestines of
      weaning pigs with IUGR, focusing on molecular mechanisms underlying altered
      immune response. Piglets with IUGR were weaned at 21 days of age and received
      orally 1.22 g alanine or 1 g glutamine per kg body weight every 12 h. Weight gain
      and intestinal weight of weaning piglets were increased by glutamine
      supplementation. Levels of serum IgG in piglets supplemented with glutamine were
      increased compared with Control piglets. The production of IL-1 and IL-8 in the
      serum and jejunum was decreased by glutamine supplementation, whereas the levels
      of IL-4 in the serum and the concentrations of IL-4 and IL-10 in the jejunum were
      increased. The expression of heat shock protein 70 (Hsp70) in the jejunum was
      increased by glutamine supplementation, but the degradation of inhibitor kappaB
      and the activity of nuclear factor-kappaB (NF-kappaB) were decreased. In
      conclusion, glutamine supplementation enhanced immune response in weaning piglets
      with IUGR. The effects of glutamine in IUGR are associated with increased Hsp70
      expression and suppression of NF-kappaB activation.

PMID- 22962946
TI  - The effects of iodine level and source on iodine carry-over in eggs and body
      tissues of laying hens.
AB  - In the presented study the effect of different iodine (I) levels and sources in
      hen feed on the iodine concentration of different tissues, blood serum, and eggs
      of laying hens was studied. For this purpose, two experiments were conducted with
      30 laying hens each. In these experiments feed was enriched with KI and
      Ca(IO(3))(2), respectively, at 0 (Control), 0.25, 0.5, 2.5 and 5 mg I/kg feed,
      resulting a analysed iodine level from 0.44 to 4.20 mg/kg feed. After four weeks
      experimental feeding the iodine concentrations of thyroid glands, blood, meat,
      liver, abdominal fat and eggs were measured with inductively coupled plasma mass
      spectrometry. The experimental treatment did not affect hen performance. The
      iodine supplementation significantly increased the iodine concentration of eggs
      (144-1304 MUg/kg), thyroid glands (3367-5975 MUg/g), blood serum (16-67 MUg/kg)
      and liver (13-43 MUg/kg). Meat (about 14 MUg I/kg) and abdominal fat (about 12
      MUg I/kg) were not significantly affected by iodine treatment. Comparative
      regression analyses showed that at a similar iodine intake, the supply via KI
      resulted in significantly higher iodine deposition into eggs than Ca(IO(3))(2).
      Due to the high carry-over of iodine into eggs, eggs may considerably contribute
      to the iodine supply of the consumers.

PMID- 22962947
TI  - The role of molecular chaperonins in warm ischemia and reperfusion injury in the
      steatotic liver: a proteomic study.
AB  - BACKGROUND: The molecular basis of the increased susceptibility of steatotic
      livers to warm ischemia/reperfusion (I/R) injury during transplantation remains
      undefined. Animal model for warm I/R injury was induced in obese Zucker rats.
      Lean Zucker rats provided controls. Two dimensional differential gel
      electrophoresis was performed with liver protein extracts. Protein features with
      significant abundance ratios (p < 0.01) between the two cohorts were selected and
      analyzed with HPLC/MS. Proteins were identified by Uniprot database. Interactive
      protein networks were generated using Ingenuity Pathway Analysis and GRANITE
      software. RESULTS: The relative abundance of 105 proteins was observed in warm
      I/R injury. Functional grouping revealed four categories of importance: molecular
      chaperones/endoplasmic reticulum (ER) stress, oxidative stress, metabolism, and
      cell structure. Hypoxia up-regulated 1, calcium binding protein 1, calreticulin,
      heat shock protein (HSP) 60, HSP-90, and protein disulfide isomerase 3 were
      chaperonins significantly (p < 0.01) down-regulated and only one chaperonin, HSP
      1 was significantly upregulated in steatotic liver following I/R. CONCLUSION:
      Down-regulation of the chaperones identified in this analysis may contribute to
      the increased ER stress and, consequently, apoptosis and necrosis. This study
      provides an initial platform for future investigation of the role of chaperones
      and therapeutic targets for increasing the viability of steatotic liver
      allografts.

PMID- 22962949
TI  - Evaluating causes of trends in long-term dissolved reactive phosphorus loads to
      Lake Erie.
AB  - Renewed harmful algal blooms and hypoxia in Lake Erie have drawn significant
      attention to phosphorus loads, particularly increased dissolved reactive
      phosphorus (DRP) from highly agricultural watersheds. We use the Soil and Water
      Assessment Tool (SWAT) to model DRP in the agriculture-dominated Sandusky
      watershed for 1970-2010 to explore potential reasons for the recent increased DRP
      load from Lake Erie watersheds. We demonstrate that recent increased storm
      events, interacting with changes in fertilizer application timing and rate, as
      well as management practices that increase soil stratification and phosphorus
      accumulation at the soil surface, appear to drive the increasing DRP trend after
      the mid-1990s. This study is the first long-term, detailed analysis of DRP load
      estimation using SWAT.

PMID- 22962948
TI  - Economic stress in childhood and adulthood, and self-rated health: a population
      based study concerning risk accumulation, critical period and social mobility.
AB  - BACKGROUND: Research in recent decades increasingly indicates the importance of
      conditions in early life for health in adulthood. Only few studies have
      investigated socioeconomic conditions in both childhood and adulthood in relation
      to health testing the risk accumulation, critical period, and social mobility
      hypotheses within the same setting. This study investigates the associations
      between economic stress in childhood and adulthood, and self-rated health with
      reference to the accumulation, critical period and social mobility hypotheses in
      life course epidemiology, taking demographic, social support, trust and lifestyle
      factors into account. METHODS: The public health survey in Skane (southern
      Sweden) in 2008 is a cross-sectional postal questionnaire study based on a random
      sample, in which 28,198 persons aged 18-80 years participated (55%
      participation). Logistic regression models were used to investigate associations
      between economic stress in childhood and adulthood, and self-rated health.
      RESULTS: Three life-course socioeconomic models concerning the association
      between economic stress and self-rated health (SRH) were investigated. The
      results showed a graded association between the combined effect of childhood and
      adulthood economic stress and poor SRH in accordance with the accumulation
      hypothesis. Furthermore, upward social mobility showed a protecting effect and
      downward mobility increased odds ratios of poor SRH in accordance with the social
      mobility hypothesis. High/severe economic stress exposures in both stages of life
      were independently associated with poor SRH in adulthood. Furthermore,
      stratifying the study population into six age groups showed similar odds ratios
      of poor SRH regarding economic stress exposure in childhood and adulthood in all
      age groups among both men and women. CONCLUSIONS: The accumulation and social
      mobility hypotheses were confirmed. The critical period model was confirmed in
      the sense that both economic stress in childhood and adulthood had independent
      effects on poor SRH. However, it was not confirmed in the sense that a particular
      window in time (in childhood or adulthood) had a specifically high impact on self
      rated health.

PMID- 22962950
TI  - Research methods and statistical techniques in addiction.

PMID- 22962951
TI  - Compulsivity as an endophenotype: the search for a hazy moving target.

PMID- 22962952
TI  - Beyond addiction or compulsion: the continuing role of environment in the case of
      pathological gambling.

PMID- 22962953
TI  - The emerging new science of psychopathology.

PMID- 22962954
TI  - Broadening our horizon: response to commentaries.

PMID- 22962955
TI  - Anthropology and addiction: an historical review.
AB  - AIMS: This paper reviews the world anthropology of drugs and alcohol use
      literature, identifying key issues addressed by anthropologists, methods and
      theoretical models in use, trends in focus over time and future directions.
      METHODS: Papers and books that comprise the literature were identified through
      computer search using the keywords: ethnography of drug use (and variants, e.g.
      drug ethnography, qualitative approaches in drug research), ethnography of
      drinking, anthropology and drug use, and anthropology and drinking. Search
      engines included Google Scholar, EBSCOHost, AnthroSource and PubMed. Identified
      sources were read and integrated into the review. RESULTS AND CONCLUSIONS: The
      literature search identified a rich and growing literature on the anthropology of
      drinking and drug use. The research and published literature on the anthropology
      of drug use has grown and diversified since the 1970s, found acceptance in the
      wider multi-disciplinary domain of alcohol and drug studies and developed beyond
      the socio-cultural model to include life-style, critical medical anthropology and
      experiential explanatory models. Anthropological research has helped to shape the
      field of addiction science, e.g. ethnographic studies show that the lived worlds
      and self-identities of drug users have cultural order and socially constructed
      purpose and meaning, and experiential research shows that some addictions or
      aspects of addictions can be affirmative, creative and sustainable, at least at
      the individual level. The human immunodeficiency virus/acquired immune deficiency
      syndrome pandemic has significantly increased anthropological research on drug
      related issues world-wide.

PMID- 22962956
TI  - Commentary on Clark (2012): contrasting medical models of alcohol problems in
      Victoria around 1900 - a response.

PMID- 22962957
TI  - Commentary on Laslett et al. (2012): integrating substance use disorder and child
      welfare interventions.

PMID- 22962958
TI  - Commentary on Kelty & Hulse (2012): is the comparison of mortality between
      patients prescribed implanted or oral naltrexone an unbiased and unconfounded
      comparison?

PMID- 22962959
TI  - Commentary on Bosker et al. (2012): Driving under the influence of cannabinoids.

PMID- 22962960
TI  - Interpreting questionnaire design effects: an update on Melson et al. (2011).

PMID- 22962961
TI  - Abusive treatment common in the USA, not just Asia.

PMID- 22962962
TI  - 100 years ago in addiction science.

PMID- 22962963
TI  - Ultralow surface recombination velocity in InP nanowires probed by terahertz
      spectroscopy.
AB  - Using transient terahertz photoconductivity measurements, we have made
      noncontact, room temperature measurements of the ultrafast charge carrier
      dynamics in InP nanowires. InP nanowires exhibited a very long photoconductivity
      lifetime of over 1 ns, and carrier lifetimes were remarkably insensitive to
      surface states despite the large nanowire surface area-to-volume ratio. An
      exceptionally low surface recombination velocity (170 cm/s) was recorded at room
      temperature. These results suggest that InP nanowires are prime candidates for
      optoelectronic devices, particularly photovoltaic devices, without the need for
      surface passivation. We found that the carrier mobility is not limited by
      nanowire diameter but is strongly limited by the presence of planar
      crystallographic defects such as stacking faults in these predominantly wurtzite
      nanowires. These findings show the great potential of very narrow InP nanowires
      for electronic devices but indicate that improvements in the crystallographic
      uniformity of InP nanowires will be critical for future nanowire device
      engineering.

PMID- 22962964
TI  - Sensitivity equation for quantitative analysis with multivariate curve resolution
      alternating least-squares: theoretical and experimental approach.
AB  - A new equation is derived for estimating the sensitivity when the multivariate
      curve resolution-alternating least-squares (MCR-ALS) method is applied to second
      order multivariate calibration data. The validity of the expression is
      substantiated by extensive Monte Carlo noise addition simulations. The
      multivariate selectivity can be derived from the new sensitivity expression.
      Other important figures of merit, such as limit of detection, limit of
      quantitation, and concentration uncertainty of MCR-ALS quantitative estimations
      can be easily estimated from the proposed sensitivity expression and the
      instrumental noise. An experimental example involving the determination of an
      analyte in the presence of uncalibrated interfering agents is described in
      detail, involving second-order time-decaying sensitized lanthanide luminescence
      excitation spectra. The estimated figures of merit are reasonably correlated with
      the analytical features of the analyzed experimental system.

PMID- 22962965
TI  - Anthropometric estimates of total and regional body fat in children aged 6-17
      years.
AB  - AIM: To develop prediction equations for total and regional (trunk, abdominal,
      arms and legs) body fat using surface anthropometric measures in children aged 6
      17 years. METHODS: This was a cross-sectional correlation study of 70 Caucasian
      children aged 6-17 years recruited from a larger randomly sampled population
      based study. The independent variables included age, mass, height, body mass
      index, waist and hip girth, and skinfold thicknesses at eight sites.
      Subscapular/triceps skinfold ratio was also calculated and entered as an
      independent variable. The dependent variables were total body percentage fat, and
      fat mass for total body, trunk, abdominal region of interest, arms and legs
      measured using dual-energy X-ray absorptiometry (DXA). Partial least squares
      regression was used to determine the best predictive equation for fat percentage
      or fat mass in each body region in each sex. RESULTS: Sex-specific prediction
      equations were developed with high coefficients of determination (r(2)), ranging
      from 0.869 to 0.936 in boys and from 0.900 to 0.979 in girls, absolute bias was
      low, and limits of agreement were narrow. CONCLUSION: Equations were developed,
      which were able to predict total and regional body fat of Caucasian children aged
      6-17 years using surface anthropometric measurements with high predictive
      accuracy.

PMID- 22962966
TI  - Induction of IL-6 and CCL5 (RANTES) in human respiratory epithelial (A549) cells
      by clinical isolates of respiratory syncytial virus is strain specific.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the major respiratory pathogen
      of infants and young children. During each seasonal epidemic, multiple strains of
      both subgroup A and B viruses circulate in the community. Like other RNA viruses,
      RSV genome replication is prone to errors that results in a heterogeneous
      population of viral strains some of which may possess differences in virulence.
      We sought to determine whether clinical isolates of RSV differ in their capacity
      to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES
      [regulated upon activation, normal T-cell expressed and secreted protein]), which
      are known to be induced in vitro and in vivo in response to RSV, during infection
      of A549 cells. RESULTS: Screening of subgroup A and B isolates revealed
      heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B
      strains, New Haven (NH)1067 and NH1125, for further analysis because of their
      marked differences in cytokine inducing properties and because subgroup B
      strains, in general, are less genetically heterogeneous as compared to subgroup A
      strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125
      differed in their capacity to induce IL-6 by an order of magnitude or more. The
      concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus
      and the concentration of these cytokines induced by NH1125 was greater than that
      of those induced by NH1067 when the multiplicity of infection of NH1067 used was
      as much as 10-fold higher than that of NH1125. The induction of IL-6 was
      dependent on viable virus as infection with UV-inactivated virus did not induce
      IL-6. The difference in IL-6 induction most likely could not be explained by
      differences in viral replication kinetics. The intracellular level of RSV RNA, as
      determined by quantitative RT-PCR, was indistinguishable between the 2 strains
      though the titer of progeny virus produced by NH1125 was greater than that
      produced by NH1067 at 16, 24 and 36 hours but essentially equal at 48 and 72
      hours. Full genome sequencing of the 2 strains revealed 193 polymorphisms and 4
      insertions in NH1067 when compared to NH1125 (2 single base insertions in non
      coding regions and 2 duplications of 3 and 60 bases in the RSV G gene). Of the
      polymorphisms, 147 occurred in coding regions and only 30 resulted in amino acid
      changes in 7 of the RSV genes. CONCLUSIONS: These data suggest that RSV strains
      may not be homogeneous with regard to pathogenesis or virulence. Identification
      of the genetic polymorphisms associated with variations in cytokine induction may
      lead to insights into RSV disease and to the development of effective antiviral
      agents and vaccines.

PMID- 22962968
TI  - The dilemma of the wounded healer.
AB  - The wounded healer is an archetype that suggests that a healer's own wounds can
      carry curative power for clients. This article reviews past research regarding
      the construct of the wounded healer. The unique benefits that a psychotherapist's
      personal struggles might have on work with clients are explored, as well as the
      potential vulnerability of some wounded healers with respect to stability of
      recovery, difficulty managing countertransference, compassion fatigue, and/or
      professional impairment. The review also explores psychologists' perceptions of
      and responses to wounded healers and examines factors relating to social stigma
      and self-stigma that may influence wounded healers' comfort in disclosing their
      wounds. We propose that the relative absence of dialogue in the field regarding
      wounded healers encourages secrecy and shame among the wounded, thereby
      preventing access to support and guidance and discouraging timely intervention
      when needed. We explore the complexities of navigating disclosure of wounds,
      given the atmosphere of silence and stigma. We suggest that the mental health
      field move toward an approach of greater openness and support regarding the
      wounded healer, and provide recommendations for cultivating the safety necessary
      to promote resilience and posttraumatic growth.

PMID- 22962967
TI  - Nanoscale graphene oxide (nGO) as artificial receptors: implications for
      biomolecular interactions and sensing.
AB  - The role of conventional graphene-oxide in biosensing has been limited to that of
      a quenching substrate or signal transducer due to size inconsistencies and poor
      supramolecular response. We overcame these issues by using nanoscale GOs (nGO) as
      artificial receptors. Unlike conventional GO, nGOs are sheets with near uniform
      lateral dimension of 20 nm. Due to its nanoscale architecture, its supramolecular
      response was enhanced, with demonstrated improvements in biomacromolecular
      affinities. This rendered their surface capable of detecting unknown proteins
      with cognizance not seen with conventional GOs. Different proteins at 100 and 10
      nM concentrations revealed consistent patterns that are quantitatively
      differentiable by linear discriminant analysis. Identification of 48 unknowns in
      both concentrations demonstrated a >95% success rate. The 10 nM detection
      represents a 10-fold improvement over analogous arrays. This demonstrates for the
      first time that the supramolecular chemistry of GO is highly size dependent and
      opens the possibility of improvement upon existing GO hybrid materials.

PMID- 22962969
TI  - A meta-analysis of psychodynamic psychotherapy outcomes: evaluating the effects
      of research-specific procedures.
AB  - The aim of this research was to examine the extent to which the use of research
      specific procedures in psychodynamic psychotherapy impacts upon treatment
      effectiveness and which variables moderate this potential relationship. Effects
      of audio/video recording of sessions, use of treatment manuals, and checks of
      treatment fidelity were examined. A meta-analysis was conducted on randomized
      controlled trials of psychodynamic psychotherapy. Forty-six independent treatment
      samples totaling 1615 patients were included. The magnitude of change between
      pretreatment and posttreatment aggregated across all studies (45 treatment
      samples) for overall outcome was large (d = 1.01), and further improvement was
      observed between posttreatment and an average 12.8-month follow-up (d = 0.18).
      Subgroup analyses comparing studies that used research-specific procedures and
      those that did not revealed that for posttreatment data no differences in
      treatment effects were found. However, the use of treatment manuals and fidelity
      checks were significantly associated with improvement between the end of
      treatment and follow-up assessment. Within the limitations of analyses, this data
      offered preliminary evidence that use of research-specific procedures does not
      contribute in a negative manner to posttreatment outcomes in psychodynamic
      psychotherapy, and their use contributes to positive differences that emerge with
      time. These findings, although observational in nature, make a case for
      reconsidering how dimensions of clinical utility and experimental control may be
      integrated in psychodynamic psychotherapy to enable further elucidation of
      principles that evidently work.

PMID- 22962970
TI  - Different processes for different therapies: therapist actions, therapeutic bond,
      and outcome.
AB  - Therapeutic bond, as a component of the alliance, is considered a common factor
      in psychotherapy; however, it may operate differently in various treatments. This
      article investigates therapist actions, particularly affect focus, in the
      formation of the bond and on reduction of symptoms in short-term dynamic
      psychotherapy (STDP) and cognitive therapy (CT) for cluster C patients. Forty-six
      cases (23 STDP and 23 CT) were assessed using the Psychotherapy Process Q-Sort,
      the Helping Alliance Questionnaire, and the Symptom Checklist 90. These scores
      were used to determine (a) therapist actions that predict formation of the bond,
      (b) the relation of the bond to symptom reduction, and (c) how therapist actions
      and bond interacted to reduce symptoms. Multiple regressions were applied to the
      total sample and to the STDP and CT cases. Psychotherapy Process Q-Sort items
      describing avoidance of affects were positively related to the bond in the total
      sample, STDP and CT. However, the relation between therapist actions, bond, and
      symptom reduction differed for the two treatments. For STDP, avoidance of affect
      suppressed the relation of bond to symptom reduction and also negatively
      influenced symptom reduction. On the other hand, in CT, avoidance of affect was
      positively related to both the formation of the bond and to symptom reduction.
      Although the bond is a common factor and important component of the alliance, it
      appears to operate differently in STDP and CT. A focus on affect is important to
      the benefits of STDP but interferes with the benefits of CT.

PMID- 22962972
TI  - Some thoughts about parallel process and psychotherapy supervision: when is a
      parallel just a parallel?
AB  - In a way not done before, Tracey, Bludworth, and Glidden-Tracey ("Are there
      parallel processes in psychotherapy supervision: An empirical examination,"
      Psychotherapy, 2011, advance online publication, doi.10.1037/a0026246) have shown
      us that parallel process in psychotherapy supervision can indeed be rigorously
      and meaningfully researched, and their groundbreaking investigation provides a
      nice prototype for future supervision studies to emulate. In what follows, I
      offer a brief complementary comment to Tracey et al., addressing one matter that
      seems to be a potentially important conceptual and empirical parallel process
      consideration: When is a parallel just a parallel?

PMID- 22962971
TI  - Supportive-expressive dynamic psychotherapy in the community mental health
      system: a pilot effectiveness trial for the treatment of depression.
AB  - The goal of the current article is to present the results of a randomized pilot
      investigation of a brief dynamic psychotherapy compared with treatment-as-usual
      (TAU) in the treatment of moderate-to-severe depression in the community mental
      health system. Forty patients seeking services for moderate-to-severe depression
      in the community mental health system were randomized to 12 weeks of
      psychotherapy, with either a community therapist trained in brief dynamic
      psychotherapy or a TAU therapist. Results indicated that blind judges could
      discriminate the dynamic sessions from the TAU sessions on adherence to dynamic
      interventions. The results indicate moderate-to-large effect sizes in favor of
      the dynamic psychotherapy over the TAU therapy in the treatment of depression.
      The Behavior and Symptom Identification Scale-24 showed that 50% of patients
      treated with dynamic therapy moved into a normative range compared with only 29%
      of patients treated with TAU.

PMID- 22962974
TI  - Empirically supported perspectives on transference.
AB  - There is much debate about the definition of transference and the use of
      transference in psychotherapy treatment. The current section brings together
      three papers presented at the American Psychological Association's Annual
      conference that bridge diverse areas of psychology and the study of transference.
      Each of these papers contributes to our understanding of what transference is,
      where it exists, and how it can influence people. The papers also shed light on
      what we still do not know about transference and our continued need to struggle
      with what transference is and is not, how it can best be used to help people, and
      how future empirical research, across psychology disciplines, is critical to move
      our field forward.

PMID- 22962975
TI  - Experiments on transference in interpersonal relations: Implications for
      treatment.
AB  - Ordinary interpersonal encounters with new people involve more than what meets
      the eye, and transference readily arises in such encounters, affecting everyday
      social perception and interpersonal responding, as well as perceptions of the
      self. Transference provides a mechanism whereby past relationships can play out
      in new ones. Research on the social-cognitive process of transference and the
      relational self clearly shows that transference occurs as a "normal" nonclinical
      process outside of the therapy setting. In this article, we review the
      theoretical framework and research approach to understanding transference, as
      well as what the evidence says about what triggers transference, how, why, and
      what the consequences of transference are as they occur, for better or for worse,
      in the context of daily living and in treatment. The clinical implications of the
      findings are also addressed, with a focus on how problematic transference
      patterns might be changed if they lead to personal suffering for the individual.

PMID- 22962976
TI  - Crossing theoretical lines: the role and effect of transference in nonanalytic
      psychotherapies.
AB  - Although the concept of transference emerged from and is embedded in
      psychoanalytic and psychodynamic psychotherapies, some believe it exists and is
      important in all psychological treatments. In the present article, we examine
      empirical evidence in response to the following questions: (1) Does transference
      exist in nonanalytic therapies? (2) If so, how does it unfold over the course of
      such therapies? (3) How does it relate to therapy process, patient
      characteristics, and outcome of these therapies? Empirical evidence supports the
      contention that transference occurs in nonanalytic therapies, that it unfolds in
      a certain manner, and that it is significantly related to treatment process and
      outcome, as well as patient characteristics. Sorely needed are studies that
      examine how transferences of different types may be effectively responded to in
      nonanalytic therapies.

PMID- 22962977
TI  - Transference, transference interpretations, and transference-focused
      psychotherapies.
AB  - The concept of transference and the use of transference interpretations in
      psychotherapy have been highly controversial topics garnering frequent attention
      both within psychoanalysis and across multiple orientations of psychotherapy. In
      this article, we review the empirical evidence as it bears on this controversy
      and discuss the implications of the evidence for psychoanalysis, psychodynamic
      psychotherapy, and therapy in general. We provide a brief historical and
      contextual overview, followed by a discussion of the development of the concept
      of transference. We then discuss the evidence for the concept of transference
      from basic psychological research and contend that these findings are not only
      consistent with a social-cognitive and information processing model, but that
      they may also indicate conflict and defensive processes suggestive of a dynamic
      transference process model. We continue with a discussion of the evidence for the
      concept of transference from psychotherapy research and examine process findings
      relating to the use of transference interpretations and transference-focused
      psychotherapies. Finally, we present the implications of this emerging evidence
      for clinical practice.

PMID- 22962978
TI  - Quality of object representations related to service utilization in a long-term
      residential treatment center.
AB  - The current study examines patient factors related to service utilization during
      intensive treatment for 66 residential patients suffering from severe mental
      illness. We examined the relationship among demographic, psychiatric severity,
      and quality of object representation variables with individual and group
      psychotherapy sessions attended and emergency department transfers. Hierarchical
      linear regression models indicate malevolent affective expectations of
      interpersonal relationships embedded in patient narratives is uniquely related to
      individual psychotherapy attendance. A three-variable model consisting of higher
      educational status, number of axis I/II disorders, and poor understanding of
      social causality was related to transfers to emergency departments owing to self
      destructive behavior. Quality of object representation of self and others was
      uniquely related to treatment use and self-destructive behaviors. Results
      highlight the importance of a comprehensive multimodal evaluation for improving
      treatment preparation, planning, and intervention. Clinical implications are
      considered.

PMID- 22962980
TI  - Assessing the influence of actinic keratosis on patients' quality of life: the
      AKQoL questionnaire.
AB  - BACKGROUND: Limited knowledge is available regarding quality of life in patients
      with actinic keratosis (AK). OBJECTIVES: To develop and validate a disease
      specific questionnaire - the Actinic Keratosis Quality of Life questionnaire
      (AKQoL) - to assess the quality of life of patients with AK. METHODS: Based on an
      extensive literature search and patient interviews, the AKQoL was developed in a
      stepwise approach. An initial mega-questionnaire was composed and subsequently
      shortened based on statistical differences between patients and controls. A test
      retest was done to establish the reliability and to refine the items further.
      Rasch analyses were performed on the final questionnaire. RESULTS: Initially, 175
      items were tested in a mega-questionnaire. The questionnaires were sent out twice
      and statistical analyses were made, reducing the number of questions to 18 and
      10, respectively. Subsequent inter-item correlations showed that one item had
      only a weak correlation to the rest of the scale. This was confirmed by the Rasch
      model and by internal consistency as evaluated by Cronbach's coefficient alpha.
      Only one item was found to provide a small sex difference. A Bland-Altman plot
      showed excellent reliability. Items are scored on a standard 4-point Likert scale
      and summarized in a total score of maximum 27 points. A higher score indicates
      greater quality of life impairment. CONCLUSIONS: A nine-item questionnaire for
      patients with AK was developed. The AKQoL has three domains covering emotions,
      function and control and one single global item. The questionnaire's scale
      structure, the content and face validity, and the reliability have been
      established.

PMID- 22962981
TI  - Effects of bariatric surgeries on obesity and comorbidities.

PMID- 22962983
TI  - Case report: bupivacaine toxicity with dorsal penile block for circumcision.

PMID- 22962985
TI  - Differentiating grief and depression in patients who are seriously ill.

PMID- 22962986
TI  - Epidural analgesia for labor pain.

PMID- 22962987
TI  - Hypothyroidism: an update.
AB  - Hypothyroidism is a clinical disorder commonly encountered by the primary care
      physician. Untreated hypothyroidism can contribute to hypertension, dyslipidemia,
      infertility, cognitive impairment, and neuromuscular dysfunction. Data derived
      from the National Health and Nutrition Examination Survey suggest that about one
      in 300 persons in the United States has hypothyroidism. The prevalence increases
      with age, and is higher in females than in males. Hypothyroidism may occur as a
      result of primary gland failure or insufficient thyroid gland stimulation by the
      hypothalamus or pituitary gland. Autoimmune thyroid disease is the most common
      etiology of hypothyroidism in the United States. Clinical symptoms of
      hypothyroidism are nonspecific and may be subtle, especially in older persons.
      The best laboratory assessment of thyroid function is a serum thyroid-stimulating
      hormone test. There is no evidence that screening asymptomatic adults improves
      outcomes. In the majority of patients, alleviation of symptoms can be
      accomplished through oral administration of synthetic levothyroxine, and most
      patients will require lifelong therapy. Combination triiodothyronine/thyroxine
      therapy has no advantages over thyroxine monotherapy and is not recommended.
      Among patients with subclinical hypothyroidism, those at greater risk of
      progressing to clinical disease, and who may be considered for therapy, include
      patients with thyroid-stimulating hormone levels greater than 10 mIU per L and
      those who have elevated thyroid peroxidase antibody titers.

PMID- 22962988
TI  - Rational use of opioids for management of chronic nonterminal pain.
AB  - Opioid prescribing for chronic nonterminal pain has increased in recent years,
      although evidence for its long-term effectiveness is weak and its potential for
      harm is significant. Nonmedical use of prescription opioids, diversion, and
      overdose deaths have also increased sharply, sparking concern about the safety of
      these medications. Physicians considering initiation or continuation of opioid
      therapy for a patient with chronic nonterminal pain should first use a structured
      approach that includes a biopsychosocial evaluation and a treatment plan that
      encourages patients to set and reach functional goals. There should be a
      comprehensive evaluation for the cause of pain, assessment for risk of opioid
      complications (including misuse and addiction), and a detailed treatment history,
      including a review of medical records and data from the state prescription
      monitoring program. Opioids should be prescribed on a trial basis, to be
      continued only if progress toward functional goals is demonstrated. Long-acting
      morphine is the preferred initial drug, although several alternatives are
      available. Ongoing monitoring for safety and effectiveness is essential,
      including regular review of functional progress or maintenance, urine drug
      testing, and surveillance of data from the state prescription monitoring program.
      Ineffective, unsafe, or diverted opioid therapy should be promptly tapered or
      stopped.

PMID- 22962989
TI  - Managing grief and depression at the end of life.
AB  - Psychological distress is common in terminally ill persons and can be a source of
      great suffering. Grief is an adaptive, universal, and highly personalized
      response to the multiple losses that occur at the end of life. This response may
      be intense early on after a loss manifesting itself physically, emotionally,
      cognitively, behaviorally, and spiritually; however, the impact of grief on daily
      life generally decreases with time. Although pharmacologic interventions are not
      warranted for uncomplicated grief, physicians are encouraged to support patients
      by acknowledging their grief and encouraging the open expression of emotions. It
      is important for the physician to distinguish uncomplicated grief reactions from
      more disabling psychiatric disorders such as major depression. The symptoms of
      grief may overlap with those of major depression or a terminal illness or its
      treatment; however, grief is a distinct entity. Feelings of pervasive
      hopelessness, helplessness, worthlessness, guilt, lack of pleasure, and suicidal
      ideation are present in patients with depression, but not in those experiencing
      grief. Psychotherapy and antidepressant medications reduce symptoms of distress
      and improve quality of life for patients with depression. Physicians may consider
      psychostimulants, such as methylphenidate, for patients who have depression with
      a life expectancy of only days to weeks.

PMID- 22962990
TI  - A better day tomorrow.

PMID- 22962991
TI  - Large growth on the face. Cutaneous horn.

PMID- 22962992
TI  - Risk stratification of children with bronchiolitis.

PMID- 22962994
TI  - Information from your family doctor. Treatment of grief and depression at the end
      of life.

PMID- 22962995
TI  - Refusal of and overcoming the Ipse dixit philosophy.

PMID- 22962997
TI  - Potential of the predatory mite, Amblyseius swirskii to suppress the broad mite,
      Polyphagotarsonemus latus on the gboma eggplant, Solanum macrocarpon.
AB  - In Benin, the tarsonemid mite Polyphagotarsonemus latus (Banks) (Prostigmata:
      Tarsonemidae) is a key pest of gboma eggplant Solanum macrocarpon (L.)
      (Solanales: Solanaceae), a leafy vegetable on which it causes considerable damage
      to the plants and substantial reduction in yield. Predatory mites in the family
      Phytoseiidae have been successfully used in the biological control of numerous
      agricultural pests worldwide. In that respect, a population of the phytoseiid
      mite Amblyseius swirskii (Athias-Henriot) (Mesostigmata: Phytoseiidae) has been
      identified as a potential predator of P. latus, and is now a candidate for
      release against this pest in Benin. The objective of the present study is to
      determine, through laboratory experiments, the predation rate and life table
      parameters of A. swirskii when feeding on P. latus or alternative food such as
      maize pollen. Under laboratory conditions the mean number of P. latus consumed by
      A. swirskii, and daily oviposition, significantly increased as the number of prey
      increased. Total development time of A. swirskii was significantly shorter when
      it fed on P. latus than on maize pollen. Net reproduction rate, intrinsic rate of
      increase, mean generation time and the finite rate of increase of A. swirskii
      were were all significantly lower on P. latus than on maize pollen. However,
      doubling time was significantly higher on maize pollen. This study shows that A.
      swirskii is a good predator of P. latus, and that maize pollen can efficiently
      sustain A. swirskii populations when P. latus densities on plants become low.
      Consequently, A. swirskii can be used for the biological control of the broad
      mite P. latus on gboma eggplant, and on other solanaceous crops in Benin and
      elsewhere.

PMID- 22962998
TI  - Impact of wire geometry in energy extraction from salinity differences using
      capacitive technology.
AB  - Energy extraction based on capacitive Donnan potential (CDP) is a recently
      suggested technique for sustainable power generation. CDP combines the use of ion
      exchange membranes and porous carbon electrodes to convert the Gibbs free energy
      of mixing sea and river water into electric work. The electrodes geometry has a
      relevant impact on internal resistance and overall performance in CDP. In this
      work, we present the first effort to use wire-shaped electrodes and its
      suitability for improving CDP. Analytical evaluation and electrical measurements
      confirm a strong nonlinear decrease in internal resistance for distances between
      electrodes smaller than 3 mm. We also demonstrated that we get more power per
      material invested when compared to traditional flat plate designs. These findings
      show the advantages of this design for further development of CDP into a mature
      technology.

PMID- 22963000
TI  - Dynamics of detachment of Escherichia coli from plasma-mediated coatings under
      shear flow.
AB  - A series of plasma-mediated coatings, containing silver nanoparticles embedded in
      an organosilicon or silica-like matrix, were deposited onto stainless steel and
      chemically characterized. Their anti-adhesive properties were evaluated in vitro
      towards Escherichia coli by performing shear-flow induced detachment experiments.
      Increasing the wall shear stress facilitated E. coli cell detachment,
      irrespective of the coating characteristics. When nanosilver was incorporated,
      cell detachment was lower, probably due to the affinity of the embedded silver
      for biological components of the cell wall. The presence of methyl groups in the
      matrix network could also promote enhanced hydrophobic interactions. Within the
      population fraction remaining attached to the coating under increasing shear
      flow, different association phenotypes were observed, viz. progressively lying
      flat, moving laterally, remaining tethered, or rotating by a single anchoring
      point, until alignment with the flow direction. This re-orientation phenotype and
      its relation with detachment were dependent of the coating. The effects of such
      heterogeneities should be more deeply explored.

PMID- 22962999
TI  - Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK
      A(y) mice.
AB  - BACKGROUND: Fucoxanthin is a xanthophyll present in brown seaweeds and has
      several beneficial effects, including anti-obesity and anti-diabetic effects.
      However, we and another group previously observed that fucoxanthin increases
      serum cholesterol levels in rodents. Cholesterol is an important component of
      cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also
      closely associated with atherosclerosis. Therefore, we sought to identify the
      mechanism underlying the increase in serum cholesterol levels by fucoxanthin.
      METHODS: Diabetic/obese KK-A(y) mice were fed a diet containing 0.2% fucoxanthin
      for 4 weeks. The mice were sacrificed, and total blood samples were collected for
      the measurement of serum total cholesterol, HDL-cholesterol and non-HDL
      cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time
      PCR and Western blotting were performed to determine hepatic mRNA and protein
      expression of genes involved in cholesterol metabolism, respectively. RESULTS:
      Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol
      levels, and reduced hepatic cholesterol content. In liver, the expression of
      SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis
      significantly increased and tended to increase in the fucoxanthin-fed mice,
      respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is
      important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver
      from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively,
      compared with the control mice. Further, we found that dietary fucoxanthin
      significantly increased the mRNA expression of proprotein convertase
      subtilisin/kexin type 9 (PCSK9), which enhances intracellular degradation of LDLR
      in lysosomes. CONCLUSIONS: Fucoxanthin increased HDL-cholesterol and non-HDL
      cholesterol levels in KK-A(y) mice by inducing SREBP expression and reduced
      cholesterol uptake in the liver via down-regulation of LDLR and SR-B1, resulted
      in increased serum cholesterol in the mice.

PMID- 22963001
TI  - Assessment of measurement properties of peak VO(2) in children with pulmonary
      arterial hypertension.
AB  - BACKGROUND: The 6-minute walk test evaluates the effect of pharmacologic
      intervention in adults with pulmonary arterial hypertension (PAH) but, for
      reasons of compliance or reliability, may not be appropriate for children at all
      ages. Thus, peak oxygen consumption (VO2, maximal exercise test) was used instead
      in a pediatric PAH trial (STARTS-1) to evaluate pharmacologic intervention with
      sildenafil. This was the first large placebo-controlled trial to use the peak VO2
      endpoint in this population. Our working hypothesis was that, as with other
      populations, percentage changes in peak VO2 in pediatric patients with PAH are
      reliable and are associated with changes in other clinical endpoints. METHODS:
      Using data from the subpopulation of 106 patients who were developmentally and
      physically able to perform exercise testing, all of whom were World Health
      Organization Functional Class (WHO FC) I, II, or III, reliability was assessed
      using the intraclass correlation coefficient and Bland-Altman plot on screening
      and baseline data. Relationships between percentage change in peak VO2 from
      baseline to end of treatment and other endpoints were evaluated using correlation
      coefficients and regression analyses. RESULTS: The intraclass correlation was
      0.79 between screening and baseline peak VO2, an agreement that was supported by
      the Bland-Altman plot. Percentage change in peak VO2 correlated well (r >=0.40)
      and showed responsiveness to a physician global assessment of change and with
      change in WHO FC (for baseline classes I and III). Percentage change in peak VO2
      did not correlate with change in the Family Cohesion of the Child Health
      Questionnaire (r = 0.04) or with a subject global assessment of change (r =
      0.12). The latter may have been influenced by child and parental-proxy response
      and instrument administration. CONCLUSION: In pediatric PAH patients who are
      developmentally and physically able to perform exercise testing, peak VO2
      measurements exhibited good reliability and improvements that were associated
      with improvements in certain other clinical endpoints, such as the WHO FC and a
      physician global assessment. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT00159913.

PMID- 22963002
TI  - Rate of change in physical fitness and quality of life and depression following
      exercise training in patients with congestive heart failure.
AB  - Exercise training appears to improve peak oxygen consumption (VO(2) ) and quality
      of life (QOL) in heart failure patients, although disease etiology, patient
      demographics and medication may alter the rate of adaptation. The authors sought
      to identify rate of change from baseline in fitness, QOL, and depression
      following exercise training in a cohort of patients with congestive heart
      failure. Thirty male systolic heart failure patients (aged 63.8+/-8.3 years,
      baseline peak VO(2) 12.2+/-4.8 mL/kg/min, left ventricular ejection fraction
      28.2+/-9.4%, New York Heart Association class II/II 22/8) undertook 52 weeks of
      exercise training, 16 weeks as an outpatient and a further 36 weeks of home
      exercise. Peak VO(2) and QOL was measured using the Minnesota Living With Heart
      Failure (MLWHF) questionnaire and depression using the Hare-Davis scale. The
      authors analyzed the rate of change in peak VO(2) and MLWHF after grouping
      patients according to clinical, demographic, and pharmacologic characteristics.
      Peak VO(2) measurements varied over time, with no effect of disease pathology or
      beta-blocker on peak VO(2) . The rate of change in physical MLWHF score was
      significantly greater (improved) during 0 to 16 weeks in patients with dilated
      pathology, but was not significantly affected by beta-blocker use or age. The
      exercise training venue and supervision, or lack thereof, is the major
      determinant of adaptation to the intervention in heart failure patients, although
      age, beta-adrenergic medication, and heart failure etiology also explain some of
      the variation in adaptive responses observed.

PMID- 22963003
TI  - Blastocystosis in patients with gastrointestinal symptoms: a case-control study.
AB  - BACKGROUND: Blastocystosis is a frequent bowel disease. We planned to to evaluate
      the prevalence of Blastocystis spp. in patients who applied to the same internal
      medicine-gastroenterology clinic with or without gastrointestinal complaints to
      reveal the association of this parasite with diagnosed IBS and IBD. METHODS: A
      total of 2334 patients with gastrointestinal symptoms composed the study group,
      which included 335 patients with diagnosed inflammatory bowel disease and 877
      with irritable bowel syndrome. Patients without any gastrointestinal symptoms or
      disease (n = 192) composed the control group. Parasite presence was investigated
      by applying native-Lugol and formol ethyl acetate concentration to stool
      specimens, and trichrome staining method in suspicious cases. RESULTS:
      Blastocystis spp. was detected in 134 patients (5.74%) in the study group and 6
      (3.12%) in the control group (p = 0.128). In the study group, Blastocystis spp.
      was detected at frequencies of 8.7% in ulcerative colitis (24/276), 6.78% in
      Crohn's disease (4/59), 5.82% in irritable bowel syndrome (51/877), and 4.9% in
      the remaining patients with gastrointestinal symptoms (55/1122). Blastocystis
      spp. was detected at a statistically significant ratio in the inflammatory bowel
      disease (odds ratio [OR] = 2.824; 95% confidence interval [CI]: 1.149-6.944; p =
      0.019) and ulcerative colitis (OR = 2.952; 95% CI: 1.183-7.367; p = 0.016)
      patients within this group compared to controls. There were no statistically
      significant differences between the control group and Crohn's disease or
      irritable bowel syndrome patients in terms Blastocystis spp. frequency (p =
      0.251, p = 0.133). CONCLUSIONS: Blastocystosis was more frequent in patients with
      inflammatory bowel disease, especially those with ulcerative colitis. Although
      symptomatic irritable bowel syndrome and Crohn's disease patients had higher
      rates of Blastocystis spp. infection, the differences were not significant when
      compared to controls.

PMID- 22963004
TI  - Effect of dimensionality on the localization behavior in hydrogenated graphene
      systems.
AB  - Recently, several experiments have shown that graphene exhibits a metal-to
      insulator transition by hydrogenation. Here we theoretically study the transport
      properties of hydrogenated graphene and graphene nanoribbons (GNRs), focusing on
      the conductance fluctuation behavior in the localized regime. Using a simple
      model for the conductance distribution in the quasi-localized regime where the
      conventional theory fails, we derive the modified single parameter scaling (SPS)
      relations for quasi-one-dimensional (Q1D) GNRs as well as two-dimensional (2D)
      graphene. We show that, as the dimensional crossover occurs from 2D to Q1D, the
      shape of the conductance distribution evolves from a positively skewed
      distribution to a log-normal distribution. We predict that GNRs with widths much
      larger than the localization lengths do not behave as a Q1D system. Our results
      provide fundamental insights into the dimensionality change not only in graphene,
      but also in general mesoscopic systems in the localized regime.

PMID- 22963005
TI  - Anti-cytokeratin CAM5.2 should not be mistaken for cytokeratin 8/18 monoclonal
      antibody: comment on "spindle cell squamous cell carcinoma not expressing
      stratified but simple epithelial cytokeratin: Efficacy of simple epithelial
      cytokeratin immunoreactivity" (Tokuriki A, Kiyohara T, Kouraba S, Kumakiri M,
      Journal of Dermatology 2012; 39: 72-75).

PMID- 22963006
TI  - Improved model quality assessment using ProQ2.
AB  - BACKGROUND: Employing methods to assess the quality of modeled protein structures
      is now standard practice in bioinformatics. In a broad sense, the techniques can
      be divided into methods relying on consensus prediction on the one hand, and
      single-model methods on the other. Consensus methods frequently perform very well
      when there is a clear consensus, but this is not always the case. In particular,
      they frequently fail in selecting the best possible model in the hard cases
      (lacking consensus) or in the easy cases where models are very similar. In
      contrast, single-model methods do not suffer from these drawbacks and could
      potentially be applied on any protein of interest to assess quality or as a
      scoring function for sampling-based refinement. RESULTS: Here, we present a new
      single-model method, ProQ2, based on ideas from its predecessor, ProQ. ProQ2 is a
      model quality assessment algorithm that uses support vector machines to predict
      local as well as global quality of protein models. Improved performance is
      obtained by combining previously used features with updated structural and
      predicted features. The most important contribution can be attributed to the use
      of profile weighting of the residue specific features and the use features
      averaged over the whole model even though the prediction is still local.
      CONCLUSIONS: ProQ2 is significantly better than its predecessors at detecting
      high quality models, improving the sum of Z-scores for the selected first-ranked
      models by 20% and 32% compared to the second-best single-model method in CASP8
      and CASP9, respectively. The absolute quality assessment of the models at both
      local and global level is also improved. The Pearson's correlation between the
      correct and local predicted score is improved from 0.59 to 0.70 on CASP8 and from
      0.62 to 0.68 on CASP9; for global score to the correct GDT_TS from 0.75 to 0.80
      and from 0.77 to 0.80 again compared to the second-best single methods in CASP8
      and CASP9, respectively. ProQ2 is available at http://proq2.wallnerlab.org.

PMID- 22963007
TI  - Lactobacillus sakei CRL1862 improves safety and protein hydrolysis in meat
      systems.
AB  - AIMS: The capacity of Lactobacillus sakei CRL1862 to prevent the growth of
      pathogens and its ability to degrade sarcoplasmic and myofibrillar proteins in
      pork meat systems was evaluated. In addition, basic safety aspects of Lact. sakei
      CRL1862 such as production of biogenic amines and antibiotic susceptibility were
      addressed. METHODS AND RESULTS: The bacteriocin-producing Lact. sakei CRL1862
      showed respectively bactericide and bacteriostatic effect against Listeria
      monocytogenes and Staphylococcus aureus in beaker sausage assay during 9 days of
      storage at 22  degrees C. The hydrolytic effect of Lact. sakei CRL1862 on protein
      extracts was evaluated by SDS-PAGE and reverse phase HPLC. A more pronounced
      proteolysis was evidenced in inoculated sarcoplasmic proteins compared with
      myofibrillar extracts with the generation of predominantly hydrophilic peptides
      and increase of total free amino acids concentration. Lactobacillus sakei CRL1862
      produced neither histamine nor tyrosine and exhibited no resistance to the
      antibiotics assayed. CONCLUSIONS: Lactobacillus sakei CRL1862 effectively
      controlled the growth of L. monocytogenes and Staph. aureus; moreover, it was
      able to hydrolyse pork meat extracts generating peptides and amino acids, which
      may improve hygienic and sensorial attributes of fermented meat products.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The use of an integrated approach to
      evaluate the major traits of Lact. sakei CRL1862 showed it can be applied as an
      autochthonous functional starter in meat fermentation.

PMID- 22963008
TI  - Double thermal transitions of type I collagen in acidic solution.
AB  - Contributed equally to this work. To further understand the origin of the double
      thermal transitions of collagen in acidic solution induced by heating, the
      denaturation of acidic soluble collagen was investigated by micro-differential
      scanning calorimeter (micro-DSC), circular dichroism (CD), dynamic laser light
      scattering (DLLS), transmission electron microscopy (TEM), and two-dimensional
      (2D) synchronous fluorescence spectrum. Micro-DSC experiments revealed that the
      collagen exhibited double thermal transitions, which were located within 31-37 
      degrees C (minor thermal transition, T(s) ~ 33  degrees C) and 37-55  degrees C
      (major thermal transition, T(m) ~ 40  degrees C), respectively. The CD spectra
      suggested that the thermal denaturation of collagen resulted in transition from
      polyproline II type structure to unordered structure. The DLLS results showed
      that there were mainly two kinds of collagen fibrillar aggregates with different
      sizes in acidic solution and the larger fibrillar aggregates (T(p2) = 40  degrees
      C) had better heat resistance than the smaller one (T(p1) = 33  degrees C). TEM
      revealed that the depolymerization of collagen fibrils occurred and the periodic
      cross-striations of collagen gradually disappeared with increasing temperature.
      The 2D fluorescence correlation spectra were also applied to investigate the
      thermal responses of tyrosine and phenylalanine residues at the molecular level.
      Finally, we could draw the conclusion that (1) the minor thermal transition was
      mainly due to the defibrillation of the smaller collagen fibrillar aggregates and
      the unfolding of a little part of triple helices; (2) the major thermal
      transition primarily arose from the defibrillation of the larger collagen
      fibrillar aggregates and the complete denaturation of the majority part of triple
      helices.

PMID- 22963009
TI  - Effects of amino acid substitutions in the VP2 B-C loop on antigenicity and
      pathogenicity of serotype Asia1 foot-and-mouth disease virus.
AB  - BACKGROUND: Foot-and-mouth disease virus (FMDV) exhibits a high degree of
      antigenic variability. Studies of the antigenic diversity and determination of
      amino acid changes involved in this diversity are important to the design of
      broadly protective new vaccines. Although extensive studies have been carried out
      to explore the molecular basis of the antigenic variation of serotype O and
      serotype A FMDV, there are few reports on Asia1 serotype FMDV. METHODS: Two
      serotype Asia1 viruses, Asia1/YS/CHA/05 and Asia1/1/YZ/CHA/06, which show
      differential reactivity to the neutralizing monoclonal antibody (nMAb) 1B4, were
      subjected to sequence comparison. Then a reverse genetics system was used to
      generate mutant versions of Asia1/YS/CHA/05 followed by comparative analysis of
      the antigenicity, growth property and pathogenicity in the suckling mice.
      RESULTS: Three amino acid differences were observed when the structural protein
      coding sequences of Asia1/1/YZ/CHA/06 were compared to that of Asia1/YS/CHA/05.
      Site-directed mutagenesis and Immunofluorescence analysis showed that the amino
      acid substitution in the B-C loop of the VP2 protein at position 72 is
      responsible for the antigenic difference between the two Asia1 FMDV strains.
      Furthermore, alignment of the amino acid sequences of VP2 proteins from serotype
      Asia1 FMDV strains deposited in GenBank revealed that most of the serotype Asia1
      FMDV strains contain an Asn residue at position 72 of VP2. Therefore, we
      constructed a mutant virus carrying an Asp-to-Asn substitution at position 72 and
      named it rD72N. Our analysis shows that the Asp-to-Asn substitution inhibited the
      ability of the rD72N virus to react with the MAb 1B4 in immunofluorescence and
      neutralization assays. In addition, this substitution decreased the growth rate
      of the virus in BHK-21 cells and decreased the virulence of the virus in suckling
      mice compared with the Asia1/YS/CHA/05 parental strain. CONCLUSIONS: These
      results suggest that variations in domains other than the hyper variable VP1 G-H
      loop (amino acid 140 to 160) are relevant to the antigenic diversity of FMDV. In
      addition, amino acid substitutions in the VP2 influenced replicative ability and
      virulence of the virus. Thus, special consideration should be given to the VP2
      protein in research on structure-function relationships and in the development of
      an FMDV vaccine.

PMID- 22963010
TI  - Low luminance visual acuity in patients with central serous chorioretinopathy.
AB  - BACKGROUND: The aim was to determine the low luminance visual acuity in eyes with
      central serous chorioretinopathy. METHODS: Seven eyes of seven patients with
      central serous chorioretinopathy and six eyes of six age-matched normal
      volunteers were examined. Low luminance visual acuity charts were created by an
      Apple Power Mac G5 computer and displayed on a cathode ray tube monitor (SONY GDM
      F500). The background luminance was set at six different levels from 78.20
      cd/m(2) to 0.37 cd/m(2). The visual acuities of the eyes with central serous
      chorioretinopathy at each of the six luminance levels were compared to those from
      their fellow eyes and to normal eyes. RESULTS: The mean visual acuities varied
      from 0.13, 0.23, 0.29, 0.42, 0.62 to 0.70 logMAR units as luminance varied from
      high to low. At the lowest luminance (0.37 cd/m(2)), five of the seven eyes could
      not read any character. The mean visual acuities of the fellow eyes at the same
      luminance levels were 0.03, 0.06, 0.11, 0.20, 0.27 and 0.45 logMAR units and
      those of the normal volunteers were 0, 0.03, 0.08, 0.14, 0.23 and 0.38 logMAR
      units, respectively. The visual acuities of the eyes with central serous
      chorioretinopathy were significantly poorer than those of the normal eyes at all
      luminance levels except 0.37 cd/m(2) (p < 0.05 for all). CONCLUSIONS: Although
      the eyes from all three groups had 0 logMAR units visual acuity under standard
      testing condition, the visual acuity of the eyes with central serous
      chorioretinopathy were significantly worse at low luminance levels. The low
      luminance visual acuity may provide information on the visual disturbances
      reported by central serous chorioretinopathy patients with 0 logMAR units visual
      acuity.

PMID- 22963011
TI  - Child maltreatment and mediating influences of childhood personality types on the
      development of adolescent psychopathology.
AB  - The purpose of this study is to investigate longitudinal risk processes linking
      early child maltreatment, childhood personality organizations, and adolescent
      maladaptation. In a sample of maltreated and nonmaltreated children (N = 400;
      62.3% African American, 11.8% Hispanic; 40.8% girls), a tripartite personality
      typology based on California Child Q-Set items representative of ego resiliency
      and ego control personality dimensions (Block & Block, 1969/1980 ) was derived at
      Wave 1 (age range = 10-12). The typology, composed of Resilient, Overcontrolled,
      and Undercontrolled profiles, was evaluated for associations with previous child
      maltreatment, and for its utility in predicting adolescent psychopathology (age
      range = 15-18). Maltreated children were significantly more likely than
      nonmaltreated children to be classified into the overcontrolled (Odds Ratio =
      1.847) and undercontrolled profiles (Odds Ratio = 2.101), compared to the
      Resilient profile. The undercontrolled profile reported higher cannabis symptoms
      and externalizing problems in adolescence than the other two profiles. The
      overcontrolled group showed the highest levels of internalizing and lowest levels
      of alcohol problems compared to the other profiles. Person-centered mediation
      analyses showed that the overcontrolled and the undercontrolled profiles
      significantly and differentially mediated the link between number of child
      maltreatment subtypes and the development of adolescent psychopathology. Child
      maltreatment is a potent environmental stressor that potentiates compromised
      personality development, eventuating in heightened psychopathology in
      adolescence. These findings have important implications for prevention and
      intervention of psychopathology and substance abuse among low income and
      maltreated youth.

PMID- 22963012
TI  - High-efficiency solution-processed Cu2ZnSn(S,Se)4 thin-film solar cells prepared
      from binary and ternary nanoparticles.
AB  - A new solution-based method to fabricate Cu(2)ZnSn(S,Se)(4) (CZTSSe) thin films
      is presented. Binary and ternary chalcogenide nanoparticles were synthesized and
      used as precursors to form CZTSSe thin films. The composition of the CZTSSe films
      can be easily controlled by adjusting the ratio of the nanoparticles used. The
      effect of compositional adjustment on device performance is illustrated.
      Laboratory-scale photovoltaic cells with 8.5% total-area efficiency (or 9.6%
      active-area efficiency) were demonstrated without anti-reflective coatings.
      Material characterization data revealed the formation of a bilayer microstructure
      during thermal processing and suggested a path forward on device improvement.

PMID- 22963014
TI  - Vitamin D status in patients with bullous pemphigoid.

PMID- 22963015
TI  - Distribution and ecology of small mammals in Albania.
AB  - In order to gain an insight into the population dynamics and habitat preferences
      of rodents in Albania, small mammals were collected during 2006-2009 in various
      districts of the country. Of the 15 species of small mammals captured (12 in
      Rodentia and 3 in Insectivora order), the yellow-necked mouse (Apodemus
      flavicollis) was the most frequently collected, representing 50% of the 325 small
      mammals captured, followed by the wood mouse (Apodemus sylvaticus) (20.62%).
      Apodemus flavicollis is the primary reservoir for Dobrava-Belgrade virus which
      causes to humans hemorrhagic fever with renal syndrome; the places with A.
      flavicollis abundance were those with records of the human disease. Knowledge of
      the reservoir ecology in a country facilitates risk assessments for rodent-borne
      diseases.

PMID- 22963016
TI  - Effects of alendronate on lumbar posterolateral fusion using hydroxyapatite in
      rabbits.
AB  - There are controversies regarding the effect of alendronate on spine fusion. In
      order to study the effects of alendronate on fusion with porous hydroxyapatite, a
      total of 47 rabbits underwent posterolateral lumbar fusion. The rabbits received
      saline (control group), alendronate 0.5 mg/kg/week (low-dose group), or
      alendronate 1 mg/kg/week (high-dose group) per oral beginning 2 weeks before
      surgery. All animals were euthanized 12 weeks after surgery, and the extent of
      fusion was assessed by radiographs, manual palpation, computed tomography (CT)
      scan, mechanical testing, and histologic examination. The fusion rates by manual
      palpation, radiography, and CT scan were similar in all groups. There was no
      significant difference in pixel optic density from the CT scan. Biomechanical
      testing showed the tensile strength of the control group was higher than that of
      the treatment group including the low- and high-dose group. In histologic
      examination, the fusion masses of control animals were characterized by a higher
      predominance of well-incorporated, trabeculated bone with a prominent marrow
      element. The treatment group showed a higher proportion of woven bone structures
      and thicker bony trabeculae. There was no significant difference in the fusion
      rate, but the tensile strength of treatment group was significantly lower.
      Histologic examination showed that alendronate inhibited bone resorption and
      remodeling.

PMID- 22963019
TI  - Strategy for facilitating advance directive completion among patients.

PMID- 22963021
TI  - Breast masses in adolescents: clinical pearls in the diagnostic evaluation.

PMID- 22963022
TI  - Evaluation of first nonfebrile seizures.
AB  - Nonfebrile seizures may indicate underlying disease or epilepsy. The patient
      history can often distinguish epileptic seizures from nonepileptic disorders by
      identifying the events directly preceding the convulsion, associated conditions,
      and details of the seizure, including triggers, length, and type of movements.
      Laboratory testing, lumbar puncture, and neuroimaging may be indicated depending
      on the presentation, suspected etiology, and patient's age.
      Electroencephalography should be performed 24 to 48 hours after a first seizure
      because of its substantial yield and ability to predict recurrence. Neuroimaging
      is recommended for adults, infants, and children who have cognitive or motor
      developmental delay or a focal seizure. Neuroimaging may be scheduled on an
      outpatient basis for patients with stable vital signs who are awake and have
      returned to neurologic baseline. Emergent neuroimaging should be performed in
      patients with persistent decreased mental status or a new focal neurologic
      abnormality. Although magnetic resonance imaging is generally preferred to head
      computed tomography because of its greater sensitivity for intracranial
      pathology, computed tomography should be performed if intracranial bleeding is
      suspected because of recent head trauma, coagulopathy, or severe headache.
      Treatment with an antiepileptic drug after a first seizure does not prevent
      epilepsy in the long term, but it decreases the short-term likelihood of a second
      seizure. Adults with an unremarkable neurologic examination, no comorbidities,
      and no known structural brain disease who have returned to neurologic baseline do
      not need to be started on antiepileptic therapy. Treatment decisions should weigh
      the benefit of decreased short-term risk of recurrence against the potential
      adverse effects of antiepileptic drugs.

PMID- 22963023
TI  - Common breast problems.
AB  - A palpable mass, mastalgia, and nipple discharge are common breast symptoms for
      which patients seek medical attention. Patients should be evaluated initially
      with a detailed clinical history and physical examination. Most women presenting
      with a breast mass will require imaging and further workup to exclude cancer.
      Diagnostic mammography is usually the imaging study of choice, but
      ultrasonography is more sensitive in women younger than 30 years. Any suspicious
      mass that is detected on physical examination, mammography, or ultrasonography
      should be biopsied. Biopsy options include fine-needle aspiration, core needle
      biopsy, and excisional biopsy. Mastalgia is usually not an indication of
      underlying malignancy. Oral contraceptives, hormone therapy, psychotropic drugs,
      and some cardiovascular agents have been associated with mastalgia. Focal breast
      pain should be evaluated with diagnostic imaging. Targeted ultrasonography can be
      used alone to evaluate focal breast pain in women younger than 30 years, and as
      an adjunct to mammography in women 30 years and older. Treatment options include
      acetaminophen and nonsteroidal anti-inflammatory drugs. The first step in the
      diagnostic workup for patients with nipple discharge is classification of the
      discharge as pathologic or physiologic. Nipple discharge is classified as
      pathologic if it is spontaneous, bloody, unilateral, or associated with a breast
      mass. Patients with pathologic discharge should be referred to a surgeon.
      Galactorrhea is the most common cause of physiologic discharge not associated
      with pregnancy or lactation. Prolactin and thyroid-stimulating hormone levels
      should be checked in patients with galactorrhea.

PMID- 22963024
TI  - Nocturnal leg cramps.
AB  - Up to 60 percent of adults report that they have had nocturnal leg cramps. The
      recurrent, painful tightening usually occurs in the calf muscles and can cause
      severe insomnia. The exact mechanism is unknown, but the cramps are probably
      caused by muscle fatigue and nerve dysfunction rather than electrolyte or other
      abnormalities. Nocturnal leg cramps are associated with vascular disease, lumbar
      canal stenosis, cirrhosis, hemodialysis, pregnancy, and other medical conditions.
      Medications that are strongly associated with leg cramps include intravenous iron
      sucrose, conjugated estrogens, raloxifene, naproxen, and teriparatide. A history
      and physical examination are usually sufficient to differentiate nocturnal leg
      cramps from other conditions, such as restless legs syndrome, claudication,
      myositis, and peripheral neuropathy. Laboratory evaluation and specialized
      testing usually are unnecessary to confirm the diagnosis. Limited evidence
      supports treating nocturnal leg cramps with exercise and stretching, or with
      medications such as magnesium, calcium channel blockers, carisoprodol, or vitamin
      B(12). Quinine is no longer recommended to treat leg cramps.

PMID- 22963025
TI  - Benign prostatic hyperplasia and male lower urinary tract symptoms.

PMID- 22963026
TI  - Rapid-onset skin rash. Guttate psoriasis.

PMID- 22963029
TI  - FPIN's clinical inquiries. Evaluation of hip pain in older adults.

PMID- 22963030
TI  - Information from your family doctor. Nocturnal leg cramps.

PMID- 22963031
TI  - Use of household water treatment and safe storage methods in acute emergency
      response: case study results from Nepal, Indonesia, Kenya, and Haiti.
AB  - Household water treatment (HWTS) methods, such as boiling or chlorination, have
      long been recommended in emergencies. While there is increasing evidence of HWTS
      efficacy in the development context, effectiveness in the acute emergency context
      has not been rigorously assessed. We investigated HWTS effectiveness in response
      to four acute emergencies by surveying 1521 targeted households and testing
      stored water for free chlorine residual and fecal indicators. We defined
      "effective use" as the percentage of the targeted population with contaminated
      household water who used the HWTS method to improve stored drinking water
      microbiological quality to internationally accepted levels. Chlorine-based
      methods were distributed in all four emergencies and filters in one emergency.
      Effective use ranged widely, from 0-67.5%, with only one pre-existing chlorine
      program in Haiti and unpromoted boiling use in Indonesia reaching >20%. More
      successful programs provided an effective HWTS method, with the necessary
      supplies and training provided, to households with contaminated water who were
      familiar with the method before the emergency. HWTS can be effective at reducing
      the risk of unsafe drinking water in the acute emergency context. Additionally,
      by focusing on whether interventions actually improve drinking water quality in
      vulnerable households, "effective use" provides an important program evaluation
      metric.

PMID- 22963032
TI  - Relationship of cardiac magnetic resonance imaging and myocardial biopsy in the
      evaluation of nonischemic cardiomyopathy.
AB  - This study was performed to determine the relative role of cardiac magnetic
      resonance (CMR) imaging and endomyocardial biopsy (EMB) in the evaluation of
      cardiomyopathy. Sixty-six patients with a clinical diagnosis of nonischemic
      dilated cardiomyopathy or restrictive cardiomyopathy underwent both EMB and CMR
      imaging as part of their diagnostic evaluation. The authors retrospectively
      reviewed the results of these two methods to determine their diagnostic impact
      and congruency. CMR imaging provided data on cardiac anatomy, left ventricular
      volumes, mass, and function in 85% of the patients, uncovered fibrosis in 31%,
      myocardial ischemia in 7%, and fibrofatty infiltration in two patients. EMB
      provided the histologic findings of cardiomyocyte hypertrophy in 77% of patients
      and substantial interstitial fibrosis in 59%. Six patients had EMB-proven amyloid
      heart disease, which was detected by CMR imaging in two. CMR imaging showed
      patterns of late gadolinium enhancement supportive of infiltrative disease or
      inflammation in 6 patients with EMB-proven definite (n=3) or borderline (n=3)
      myocarditis, but failed to do so in two other patients with borderline and two
      with resolving myocarditis. At the present time, CMR imaging and EMB remain
      complementary procedures in the evaluation of cardiomyopathic conditions.

PMID- 22963033
TI  - Early nocturnal meal skipping alters the peripheral clock and increases
      lipogenesis in mice.
AB  - BACKGROUND: In humans, skipping meals, especially breakfast, has been associated
      with obesity and other related syndromes. Recent studies in rodents suggest that
      fasting and feeding times are potential factors that affect the peripheral
      circadian clocks and metabolism. However, the link between fasting and obesity in
      rodents has yet to be fully demonstrated. METHOD: We conducted early nocturnal
      fasting (ENF) from zeitgeber time (ZT) 12 to 18 for 4 consecutive days in C57B6
      mice. The first set of experiments was performed under ad libitum conditions,
      where ENF and free-feeding (FF) control groups were compared. The second set was
      performed under isocaloric adjustment by restricting the diet to 90% of the basal
      intake of ENF mice. Calorie-restricted ENF (ENF-CR) mice were then compared with
      isocaloric controls (IC-control). Body weight, food intake, core body
      temperature, activity, adiposity, and clock-related gene expression levels in the
      liver and adipose tissues were investigated. A stable isotopic analysis was also
      conducted to estimate de novo lipogenesis fluxes. RESULTS: In the ad libitum
      condition, the ENF mice ate more during the day, increased their overall daily
      food intake and gained more weight than FF-control mice. The amplitude of the
      body core temperature rhythm in ENF mice was also lower than in the FF-controls.
      Under isocaloric conditions, ENF-CR attenuated the CR-induced body weight loss,
      compared with the IC-control. ENF-CR also altered the acrophase time of the
      expression of the clock genes, which is associated with time-shift of genes
      involved in lipid metabolism and increased lipogenesis, compared with the IC
      control. CONCLUSIONS: ENF in nocturnal mice disturbs the peripheral clock and
      increases de novo lipid synthesis and results in a predisposition to obesity.

PMID- 22963034
TI  - Functional polymer brushes via surface-initiated atom transfer radical graft
      polymerization for combating marine biofouling.
AB  - Dense and uniform polymer brush coatings were developed to combat marine
      biofouling. Nonionic hydrophilic, nonionic hydrophobic, cationic, anionic and
      zwitterionic polymer brush coatings were synthesized via surface-initiated atom
      transfer radical polymerization (SI-ATRP) of 2-hydroxyethyl methacrylate,
      2,3,4,5,6-pentafluorostyrene, 2-(methacryloyloxy)ethyl trimethylammonium
      chloride, 4-styrenesulfonic acid sodium and N,N'-dimethyl-(methylmethacryloyl
      ethyl) ammonium propanesulfonate, respectively. The functionalized surfaces had
      different efficacies in preventing adsorption of bovine serum albumin (BSA),
      adhesion of the Gram-negative bacterium Pseudomonas sp. NCIMB 2021 and the Gram
      positive Staphylococcus aureus, and settlement of cyprids of the barnacle
      Amphibalanus amphitrite (=Balanus amphitrite). The nonionic hydrophilic, anionic
      and zwitterionic polymer brushes resisted BSA adsorption during a 2 h exposure
      period. The nonionic hydrophilic, cationic and zwitterionic brushes exhibited
      resistance to bacterial fouling (24 h exposure) and cyprid settlement (24 and 48
      h incubation). The hydrophobic brushes moderately reduced protein adsorption, and
      bacteria and cyprid settlement. The anionic brushes were least effective in
      preventing attachment of bacteria and barnacle cyprids. Thus, the best approach
      to combat biofouling involves a combination of nonionic hydrophilic and
      zwitterionic polymer brush coatings on material surfaces.

PMID- 22963035
TI  - CD8-positive granulomatous mycosis fungoides mimicking generalized granuloma
      annulare.

PMID- 22963036
TI  - Oxyanionic sigmatropic rearrangements relevant to cyclooctadienone formation in
      penostatins I and F.
AB  - The results of several experiments designed to probe the energetic viability of a
      reaction path for generation of penostatins I (3) and F (4) via spontaneous [3,3]
      sigmatropic rearrangement are reported. In particular, the enolate derived from
      the 2-vinyl-6-acyldihydropyran 8-cis gave cyclooctadienone 12 via facile anionic
      oxy-Claisen rearrangement, demonstrating the feasibility of such an event.

PMID- 22963037
TI  - Fat content, energy value and fatty acid profile of donkey milk during lactation
      and implications for human nutrition.
AB  - BACKGROUND AND AIMS: Milk contains numerous nutrients. The content of n-3 fatty
      acids, the n-6/n-3 ratio, and short- and medium-chain fatty acids may promote
      positive health effects. In Western societies, cow's milk fat is perceived as a
      risk factor for health because it is a source of a high fraction of saturated
      fatty acids. Recently, there has been increasing interest in donkey's milk. In
      this work, the fat and energetic value and acidic composition of donkey's milk,
      with reference to human nutrition, and their variations during lactation, were
      investigated. We also discuss the implications of the acidic profile of donkey's
      milk on human nutrition. METHODS: Individual milk samples from lactating jennies
      were collected 15, 30, 45, 60, 90, 120, 150, 180 and 210days after foaling, for
      the analysis of fat, proteins and lactose, which was achieved using an infrared
      milk analyser, and fatty acids composition by gas chromatography. RESULTS: The
      donkey's milk was characterised by low fat and energetic (1719.2kJ.kg-1) values,
      a high polyunsaturated fatty acids (PUFA) content of mainly alpha-linolenic acid
      (ALA) and linoleic acid (LA), a low n-6 to n-3 FA ratio or LA/ALA ratio, and
      advantageous values of atherogenic and thrombogenic indices. Among the minor
      PUFA, docosahesaenoic (DHA), eicosapentanoic (EPA), and arachidonic (AA) acids
      were present in very small amounts (<1%). In addition, the AA/EPA ratio was low
      (0.18). The fat and energetic values decreased (P < 0.01) during lactation.The
      fatty acid patterns were affected by the lactation stage and showed a decrease (P
      < 0.01) in saturated fatty acids content and an increase (P < 0.01) in the
      unsaturated fatty acids content. The n-6 to n-3 ratio and the LA/ALA ratio were
      approximately 2:1, with values <1 during the last period of lactation, suggesting
      the more optimal use of milk during this period. CONCLUSIONS: The high level of
      unsaturated/saturated fatty acids and PUFA-n3 content and the low n-6/n-3 ratio
      suggest the use of donkey's milk as a functional food for human nutrition and its
      potential utilisation for infant nutrition as well as adult diets, particular for
      the elderly.

PMID- 22963038
TI  - Community dynamics of carrion flies and their parasitoids in experimental
      carcasses in central Argentina.
AB  - Insects are the predominant group regarding both species richness and abundance
      that develop on carrion. Among them, the most important decomposers using carrion
      as a source of food for their development are the immature stages of the dipteran
      families Calliphoridae, Muscidae, and Sarcophagidae. The large numbers of their
      larvae in carcasses are attacked by a rich community of parasitoids, including
      species of Braconidae, Ichneumonidae, and Pteromalidae (Hymenoptera: Parasitica).
      The objective of this study was describing the temporal composition and dynamics
      of a parasitoid community in relation to their dipterans hosts in carrion in
      terms of number of species and specific composition, irrespective of the
      particular interactions between species in both trophic levels. Additionally,
      seasonality of the climate in the region was investigated as a factor structuring
      the studied communities. The experiments were undertaken in the south of Cordoba,
      Argentina during 2004 in a rural area. Two traps per season were placed
      separately approximately 300 m from each other in the study site. Each trap
      contained a domestic pig (Sus scrofa) of approximately 8 kg as bait. Samples were
      taken daily during the first four weeks and then every two or three days over the
      following weeks until the end of the experiment. The dipteran community was
      represented by 15 species in 6 families of the Calyptratae Diptera whereas
      parasitoids belonged to six families of the parasitic Apocrita Hymenoptera.
      Climatic seasonality was an important factor in determining the number of
      occurring species in the carcasses and community composition. The highest number
      of species was observed in the spring for both communities.

PMID- 22963039
TI  - The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with
      KL-6, surfactant protein-A and surfactant protein-D.
AB  - BACKGROUND: Napsin A, an aspartic protease, is mainly expressed in alveolar type
      II cells and renal proximal tubules and is a putative immunohistochemical marker
      for pulmonary adenocarcinomas. This study sought to determine whether napsin A
      could be measured in the serum to evaluate its relationship to idiopathic
      pulmonary fibrosis (IPF) and determine whether renal dysfunction might affect
      serum napsin A levels. METHODS: Serum levels of napsin A were measured in 20
      patients with IPF, 34 patients with lung primary adenocarcinoma, 12 patients with
      kidney diseases, and 20 healthy volunteers. Surfactant protein (SP)-A, SP-D, and
      Krebs von den Lungen-6 (KL-6) levels in serum and pulmonary function tests were
      also evaluated in IPF patients. RESULTS: Circulating levels of napsin A were
      increased in patients with IPF, as compared with healthy controls, and they
      correlated with the severity of disease. Moreover, the serum napsin A levels were
      not elevated in patients with pulmonary adenocarcinoma or renal dysfunction. The
      distinguishing point between IPF and the controls was that the area under the
      receiver operating characteristic curve (ROC) of napsin A was larger than that of
      KL-6, SP-A, or SP-D. CONCLUSION: These findings suggest that serum napsin A may
      be a candidate biomarker for IPF.

PMID- 22963040
TI  - Development and validation of the Greek version of the MNREAD acuity chart.
AB  - BACKGROUND: The aim of this study was to develop MNREAD acuity charts in the
      Greek language (MNREAD-GR) and establish their repeatability in a normal-sighted
      population. METHODS: One hundred and eighty Greek sentences were constructed
      based on the design principles of the Minnesota Low Vision Reading Test. The
      software used to validate them for width was adjusted to the parameters of the
      non-Latin characters used in the Greek language (MNTest-GR) and width-validated
      sentences were then checked for literacy by two language teachers. Pilot testing
      followed in 20 adults and two groups of 20 children. Subsequently, three versions
      of the MNREAD-GR chart were printed and validated for repeatability: 20 adults
      read MNREAD-GR charts 1, 2 and 3 in random order over two sessions. A linear
      mixed-model analysis was performed for near visual acuity (VA), maximum reading
      speed and critical print size to identify the contribution of each source
      (individual subject, session, chart and residual error) to the total variance.
      Subject variance determined the intraclass correlation coefficient. RESULTS: One
      hundred of the initial 180 sentences were validated with MNTest-GR and approved
      for literacy correctness. Of those, 57 sentences were selected after pilot
      testing, and used in the final printed chart in random distribution among three
      versions. The intraclass correlation coefficients were 0.72 for VA, 0.87 for
      maximum reading speed and 0.46 for critical print size. The between-charts within
      session within-subject component accounted for a maximum five per cent of the
      variance. The between-sessions within-subject component had a maximum of one per
      cent. The coefficient of repeatability was 0.08 logMAR for VA, 46.96 words per
      minute for maximum reading speed and 0.10 logMAR for critical print size.
      CONCLUSION: The created MNREAD-GR acuity chart is a standardised clinical test
      that can be used reliably to measure near acuity, reading speed and critical
      print size in Greek-speaking literate patients of all ages.

PMID- 22963041
TI  - Surveillance on secular trends of incidence and mortality for device-associated
      infection in the intensive care unit setting at a tertiary medical center in
      Taiwan, 2000-2008: a retrospective observational study.
AB  - BACKGROUND: Device-associated infection (DAI) plays an important part in
      nosocomial infection. Active surveillance and infection control are needed to
      disclose the specific situation in each hospital and to cope with this problem
      effectively. We examined the rates of DAI by antimicrobial-resistant pathogens,
      and 30-day and in-hospital mortality in the intensive care unit (ICU). METHODS:
      Prospective surveillance was conducted in a mixed medical and surgical ICU at a
      major teaching hospital from 2000 through 2008. Trend analysis was performed and
      logistic regression was used to assess prognostic factors of mortality. RESULTS:
      The overall rate of DAIs was 3.03 episodes per 1000 device-days. The most common
      DAI type was catheter-associated urinary tract infection (3.76 per 1000 urinary
      catheter-days). There was a decrease in DAI rates in 2005 and rates of ventilator
      associated pneumonia (VAP, 3.18 per 1000 ventilator-days) have remained low since
      then (p < 0.001). The crude rates of 30-day (33.6%) and in-hospital (52.3%)
      mortality, as well as infection by antibiotic-resistant VAP pathogens also
      decreased. The most common antimicrobial-resistant pathogens were methicillin
      resistant Staphylococcus aureus (94.9%) and imipenem-resistant Acinetobacter
      baumannii (p < 0.001), which also increased at the most rapid rate. The rate of
      antimicrobial resistance among Enterobacteriaceae also increased significantly (p
      < 0.05). After controlling for potentially confounding factors, the DAI was an
      independent prognostic factor for both 30-day mortality (OR 2.51, 95% confidence
      interval [CI] 1.99-3.17, p = 0.001) and in-hospital mortality (OR 3.61, 95% CI
      2.10-3.25, p < 0.001). CONCLUSIONS: The decrease in the rate of DAI and infection
      by resistant bacteria on the impact of severe acute respiratory syndrome can be
      attributed to active infection control and improved adherence after 2003.

PMID- 22963042
TI  - Perceived barriers to help-seeking among parents of at-risk kindergarteners in
      rural communities.
AB  - This study examined help-seeking and perceived barriers to children's mental
      health service utilization in a large sample of parents living in rural
      communities who are at various stages in the help-seeking process. The goals were
      to (a) obtain a demographic profile of at-risk kindergarteners and their parents,
      (b) examine parent-reported help-seeking behaviors, and (c) assess barriers to
      mental health service use. Parent and teacher report of the Behavior Assessment
      System for Children, Second Edition, were used to screen children (N = 597) at
      kindergarten entry and to identify their risk status. Parents also completed the
      Barriers to Participation Scale and reported the frequency of help-seeking
      behaviors related to their child's problems. Using a cutoff score of 1.5 standard
      deviations above the mean, nearly half (51%) of children were identified as at
      risk (76% low risk, 24% high risk) for emotional, behavioral, social, and
      adaptive problems. Barriers and help-seeking did not differ across parents of low
      and high risk children. Among parents of at-risk children, only 33% believed
      their child had a problem. Parents sought informal help more often than
      professional help; however, medical doctors and school staff were sought most
      among professionals. The majority of parents (61%) endorsed at least one barrier
      that would interfere with mental health service use. Results highlight the
      importance of early school mental health screening and the need for interventions
      to increase parent problem recognition and engagement in mental health service
      utilization.

PMID- 22963043
TI  - Microbial source tracking to identify human and ruminant sources of faecal
      pollution in an ephemeral Florida river.
AB  - AIMS: Levels and sources of faecal indicator bacteria (FIB) in an ephemeral
      Florida river were assessed under different rainfall/flow patterns to explore the
      effects of rainfall on water quality. METHODS AND RESULTS: Quantitative PCR for
      sewage markers [human-associated Bacteroides HF183 and human polyomaviruses
      (HPyVs)] and PCR for ruminant faecal markers were used to explore contamination
      sources. Escherichia coli, faecal coliform and enterococci levels consistently
      exceeded recreational water quality criteria, and sediment FIB levels were about
      100-fold higher compared with water. HPyVs detections cooccurred with HF183,
      which was frequently detected near septic systems. Ruminant markers were detected
      only in livestock-grazing areas. Significantly greater faecal coliform and E.
      coli concentrations were observed under no-flow conditions and the levels of
      faecal coliforms in water column and sediments were negatively correlated with
      duration since last rain event. CONCLUSIONS: Septic systems and cattle grazing in
      this watershed contributed to the formation of FIB reservoirs in sediments, which
      were persistent following prolonged rainfall. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Ephemeral water bodies that flow only under the direct influence of recent
      rainfall are rarely studied. FIB levels in the New River in Florida were greater
      during dry weather than wet weather, which contrasts with most observations and
      may be attributed to bacterial reservoirs formed in still pool, sediments and
      water-saturated soils in this subtropical environment.

PMID- 22963044
TI  - Pretreatment of hepatocyte growth factor gene transfer mediated by octaarginine
      peptide-modified nanoparticles ameliorates LPS/D-galactosamine-induced hepatitis.
AB  - We previously reported that an octaarginine- and pH-sensitive fusogenic peptide
      modified multifunctional envelope-type nano device (R8-GALA-MEND) produces a high
      level of gene expression in the liver. In this study, we report on an examination
      of whether this gene delivery system exerts potent hepatoprotective effects
      against lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver
      injury. In vivo-jetPEI(TM)-Gal, a commercially available in vivo transfection
      reagent, was used as a reference. The systemic administration of the R8-GALA-MEND
      or in vivo-jetPEI(TM)-Gal showed that the latter was more toxic than the R8-GALA
      MEND, indicating that R8-GALA-MEND is a safer system than in vivo-jetPEI(TM)-Gal.
      Pretreatment with R8-GALA-MEND or in vivo-jetPEI(TM)-Gal loaded with hepatocyte
      growth factor (HGF) pDNA inhibited serum GPT and GOT levels from becoming
      elevated. However, the survival rate of the mice was significantly enhanced in
      the case of R8-GALA-MEND, but not for the in vivo-jetPEI(TM)-Gal treatment. These
      results demonstrate that R8-GALA-MEND has the potential for use in the
      pretreatment of an acute liver injury.

PMID- 22963045
TI  - Children's eyewitness memory: repeating post-event misinformation reduces the
      distinctiveness of a witnessed event.
AB  - Children may incorporate misinformation into reports of witnessed events,
      particularly if the misinformation is repeated. One explanation is that the
      misinformation trace is strengthened by repetition. Alternatively, repeating
      misinformation may reduce the discriminability between event and misinformation
      sources, increasing interference between them. We tested trace strength and
      distinctiveness accounts by showing 5- and 6-year-olds an event and then
      presenting either the "same" or "varying" items of post-event misinformation
      across three iterations. Performance was compared to a baseline in which
      misinformation was presented once. Repeating the same misinformation increased
      suggestibility when misinformation was erroneously attributed to both event and
      misinformation sources, supporting a trace strength interpretation. However,
      suggestibility measured by attributing misinformation solely to the event, was
      lower when misinformation was presented repeatedly rather than once. In contrast,
      identification of the correct source of the event was less likely if the
      misinformation was repeated, whether the same or different across iterations.
      Thus a reduction in the distinctiveness of sources disrupted memory for the event
      source. Moreover, there was strong association between memory for the event and a
      measure of distinctiveness of sources, which takes into account both the number
      of confusable source and their apparent temporal spacing from the point of
      retrieval.

PMID- 22963046
TI  - Covalent attachment of catalyst molecules to conductive diamond: CO2 reduction
      using "smart" electrodes.
AB  - We report here covalent attachment of a catalytically active cobalt complex onto
      boron-doped, p-type conductive diamond. Peripheral acetylene groups were appended
      on a cobalt porphyrin complex, and azide-alkyne cycloaddition was used for
      covalent linking to a diamond surface decorated with alkyl azides. The
      functionalized surface was characterized by X-ray photoelectron spectroscopy and
      Fourier transform IR spectroscopy, and the catalytic activity was characterized
      using cyclic voltammetry and FTIR. The catalyst-modified diamond surfaces were
      used as "smart" electrodes exhibiting good stability and electrocatalytic
      activity for electrochemical reduction of CO(2) to CO in acetonitrile solution.

PMID- 22963047
TI  - Enhanced bromate formation during chlorination of bromide-containing waters in
      the presence of CuO: catalytic disproportionation of hypobromous acid.
AB  - Bromate (BrO(3)(-)) in drinking water is traditionally seen as an ozonation
      byproduct from the oxidation of bromide (Br(-)), and its formation during
      chlorination is usually not significant. This study shows enhanced bromate
      formation during chlorination of bromide-containing waters in the presence of
      cupric oxide (CuO). CuO was effective to catalyze hypochlorous acid (HOCl) or
      hypobromous acid (HOBr) decay (e.g., at least 10(4) times enhancement for HOBr at
      pH 8.6 by 0.2 g L(-1) CuO). Significant halate concentrations were formed from a
      CuO-catalyzed hypohalite disproportionation pathway. For example, the chlorate
      concentration was 2.7 +/- 0.2 MUM (225.5 +/- 16.7 MUg L(-1)) after 90 min for
      HOCl (C(o) = 37 MUM, 2.6 mg L(-1) Cl(2)) in the presence of 0.2 g L(-1) CuO at pH
      7.6, and the bromate concentration was 6.6 +/- 0.5 MUM (844.8 +/- 64 MUg L(-1))
      after 180 min for HOBr (C(o) = 35 MUM) in the presence of 0.2 g L(-1) CuO at pH
      8.6. The maximum halate formation was at pHs 7.6 and 8.6 for HOCl or HOBr,
      respectively, which are close to their corresponding pK(a) values. In a HOCl-Br(
      )-CuO system, BrO(3)(-) formation increases with increasing CuO doses and initial
      HOCl and Br(-) concentrations. A molar conversion (Br(-) to BrO(3)(-)) of up to
      (90 +/- 1)% could be achieved in the HOCl-Br(-)-CuO system because of recycling
      of Br(-) to HOBr by HOCl, whereas the maximum BrO(3)(-) yield in HOBr-CuO is only
      26%. Bromate formation is initiated by the formation of a complex between CuO and
      HOBr/OBr(-), which then reacts with HOBr to generate bromite. Bromite is further
      oxidized to BrO(3)(-) by a second CuO-catalyzed process. These novel findings may
      have implications for bromate formation during chlorination of bromide-containing
      drinking waters in copper pipes.

PMID- 22963048
TI  - Left-sided catheter ablations preferably are performed with open irrigation.

PMID- 22963049
TI  - Coupled mutation finder: a new entropy-based method quantifying phylogenetic
      noise for the detection of compensatory mutations.
AB  - BACKGROUND: The detection of significant compensatory mutation signals in
      multiple sequence alignments (MSAs) is often complicated by noise. A challenging
      problem in bioinformatics is remains the separation of significant signals
      between two or more non-conserved residue sites from the phylogenetic noise and
      unrelated pair signals. Determination of these non-conserved residue sites is as
      important as the recognition of strictly conserved positions for understanding of
      the structural basis of protein functions and identification of functionally
      important residue regions. In this study, we developed a new method, the Coupled
      Mutation Finder (CMF) quantifying the phylogenetic noise for the detection of
      compensatory mutations. RESULTS: To demonstrate the effectiveness of this method,
      we analyzed essential sites of two human proteins: epidermal growth factor
      receptor (EGFR) and glucokinase (GCK). Our results suggest that the CMF is able
      to separate significant compensatory mutation signals from the phylogenetic noise
      and unrelated pair signals. The vast majority of compensatory mutation sites
      found by the CMF are related to essential sites of both proteins and they are
      likely to affect protein stability or functionality. CONCLUSIONS: The CMF is a
      new method, which includes an MSA-specific statistical model based on multiple
      testing procedures that quantify the error made in terms of the false discovery
      rate and a novel entropy-based metric to upscale BLOSUM62 dissimilar compensatory
      mutations. Therefore, it is a helpful tool to predict and investigate
      compensatory mutation sites of structural or functional importance in proteins.
      We suggest that the CMF could be used as a novel automated function prediction
      tool that is required for a better understanding of the structural basis of
      proteins. The CMF server is freely accessible at http://cmf.bioinf.med.uni
      goettingen.de.

PMID- 22963050
TI  - Stabilization of multiple metastatic epithelioid sarcoma under treatment with
      sunitinib malate.

PMID- 22963051
TI  - Fe electron transfer and atom exchange in goethite: influence of Al-substitution
      and anion sorption.
AB  - The reaction of Fe(II) with Fe(III) oxides and hydroxides is complex and includes
      sorption of Fe(II) to the oxide, electron transfer between sorbed Fe(II) and
      structural Fe(III), reductive dissolution coupled to Fe atom exchange, and, in
      some cases mineral phase transformation. Much of the work investigating electron
      transfer and atom exchange between aqueous Fe(II) and Fe(III) oxides has been
      done under relatively simple aqueous conditions in organic buffers to control pH
      and background electrolytes to control ionic strength. Here, we investigate
      whether electron transfer is influenced by cation substitution of Al(III) in
      goethite and the presence of anions such as phosphate, carbonate, silicate, and
      natural organic matter. Results from (57)Fe Mossbauer spectroscopy indicate that
      both Al-substitution (up to 9%) and the presence of common anions (PO(4)(3-),
      CO(3)(2-), SiO(4)(4-), and humic acid) does not inhibit electron transfer between
      aqueous Fe(II) and Fe(III) in goethite under the conditions we studied. In
      contrast, sorption of a long-chain phospholipid completely shuts down electron
      transfer. Using an enriched isotope tracer method, we found that Al-substitution
      in goethite (10%), does, however, significantly decrease the extent of atom
      exchange between Fe(II) and goethite (from 43 to 12%) over a month's time.
      Phosphate, somewhat surprisingly, appears to have little effect on the rate and
      extent of atom exchange between aqueous Fe(II) and goethite. Our results show
      that electron transfer between aqueous Fe(II) and solid Fe(III) in goethite can
      occur under wide range of geochemical conditions, but that the extent of redox
      driven Fe atom exchange may be dependent on the presence of substituting cations
      such as Al.

PMID- 22963052
TI  - Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and
      pharmacological evaluation of nanomolar inhibitors of trypanosomal
      phosphodiesterase B1.
AB  - Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an
      important role in the life cycle of Trypanosoma brucei, the causative parasite of
      human African trypanosomiasis (HAT), also known as African sleeping sickness. We
      used homology modeling and docking studies to guide fragment growing into the
      parasite-specific P-pocket in the enzyme binding site. The resulting catechol
      pyrazolinones act as potent TbrPDEB1 inhibitors with IC50 values down to 49 nM.
      The compounds also block parasite proliferation (e.g., VUF13525 (20b): T. brucei
      rhodesiense IC50 = 60 nM, T. brucei brucei IC50 = 520 nM, T. cruzi = 7.6 MUM),
      inducing a typical multiple nuclei and kinetoplast phenotype without being
      generally cytotoxic. The mode of action of 20b was investigated with
      recombinantly engineered trypanosomes expressing a cAMP-sensitive FRET sensor,
      confirming a dose-response related increase of intracellular cAMP levels in
      trypanosomes. Our findings further validate the TbrPDEB family as
      antitrypanosomal target.

PMID- 22963053
TI  - Evaluation of organochlorine pesticides in breast milk samples in Turkey applying
      features of the partial order technique.
AB  - Exposure data to organochlorine pesticides (OCPs) of mothers' breast milk samples
      were measured in different locations in the Taurus Mountains/Turkey. Villages at
      five altitudes were looked upon. The data analysis method applied is the Hasse
      diagram technique, based on Discrete Mathematics. For each of the five regions,
      one Hasse diagram was calculated and showed the same maximal object, namely, p-p'
      Dichlorodiphenyldichloroethane (DDE). In a further data investigation step, we
      performed the similarity analyses of the locations in order to quantify the
      similarities and incomparabilities. It was revealed that no correlation exists
      between most altitudes and the pattern of contamination of breast milk samples.
      The two lowest situated areas, Sahil at sea level and Ciftlikkoy at 121 m above
      sea level were similar. We reduced the datasets by applying the interval analysis
      followed by similarity analyses. We observed that endrin (END1), mirex (MIRE),
      and pentachlorobenzene (PECB) reduce most severely the similarity.

PMID- 22963054
TI  - Consider postural orthostatic tachycardia syndrome in patients with syncope.

PMID- 22963055
TI  - Heavy metal poisoning should be recognized as a cause of hypertension in
      children.

PMID- 22963057
TI  - Should family physicians use coronary artery calcium scores to screen for
      coronary artery disease? Yes: screening improves CAD risk management in selected
      patients.

PMID- 22963058
TI  - Should family physicians use coronary artery calcium scores to screen for
      coronary artery disease? No: screening is unproven, expensive, and potentially
      harmful.

PMID- 22963059
TI  - Amphetamines for attention-deficit/hyperactivity disorder in adults.

PMID- 22963060
TI  - Weight loss for patients with nonalcoholic fatty liver disease.

PMID- 22963061
TI  - Diagnosis and management of IBS in adults.
AB  - Irritable bowel syndrome is defined as abdominal discomfort or pain associated
      with altered bowel habits for at least three days per month in the previous three
      months, with the absence of organic disease. In North America, the prevalence of
      irritable bowel syndrome is 5 to 10 percent with peak prevalence from 20 to 39
      years of age. Abdominal pain is the most common symptom and often is described as
      a cramping sensation. The absence of abdominal pain essentially excludes
      irritable bowel syndrome. Other common symptoms include diarrhea, constipation,
      or alternating diarrhea and constipation. The goals of treatment are symptom
      relief and improved quality of life. Exercise, antibiotics, antispasmodics,
      peppermint oil, and probiotics appear to improve symptoms. Over-the-counter
      laxatives and antidiarrheals may improve stool frequency but not pain. Treatment
      with antidepressants and psychological therapies are also effective for improving
      symptoms compared with usual care. Lubiprostone is effective for the treatment of
      constipation-predominant irritable bowel syndrome, and alosetron (restrictions
      for use apply in the United States) and tegaserod (available only for emergency
      use in the United States) are approved for patients with severe symptoms in whom
      conventional therapy has been ineffective.

PMID- 22963062
TI  - Syphilis: a reemerging infection.
AB  - Rates of primary and secondary syphilis have increased in the past decade,
      warranting renewed attention to the diagnosis and treatment of this disease. Men
      who have sex with men are particularly affected; however, increases in infection
      rates have also been noted in women, as well as in all age groups and
      ethnicities. Physicians need to vigilantly screen high-risk patients. The
      concurrent rise in congenital syphilis also requires special attention and
      reemphasizes the need for continued early prenatal care and syphilis screening
      for all pregnant women. Syphilis infection in patients coinfected with human
      immunodeficiency virus has also become more common. New experimental diagnostic
      approaches, including using the B cell chemoattractant chemokine (CXC motif)
      ligand 13 as a cerebrospinal fluid marker, may help identify suspected
      neurosyphilis cases. Additionally, point-of-care immunochromatographic strip
      testing has been suggested for screening high-risk populations in developing
      countries. Nontreponemal screening tests followed by treponemal confirmatory
      tests continue to be standard diagnostics; however, interpreting false-negative
      and false-positive test results, and identifying serofast reactions, can be
      challenging. Although doxycycline, tetracycline, ceftriaxone, and azithromycin
      have been used to successfully treat syphilis, penicillin remains the drug of
      choice in all stages of infection and is the therapy recommended by the Centers
      for Disease Control and Prevention. Close follow-up is necessary to ensure
      treatment success.

PMID- 22963063
TI  - Treatment of childhood and adolescent depression.
AB  - Major depressive disorder in children and adolescents is a common condition that
      affects physical, emotional, and social development. Risk factors include a
      family history of depression, parental conflict, poor peer relationships,
      deficits in coping skills, and negative thinking. Diagnostic criteria are the
      same for children and adults, with the exception that children and adolescents
      may express irritability rather than sad or depressed mood, and weight loss may
      be viewed in terms of failure to reach appropriate weight milestones. Treatment
      must take into account the severity of depression, suicidality, developmental
      stage, and environmental and social factors. Cognitive behavior therapy and
      interpersonal therapy are recommended for patients with mild depression and are
      appropriate adjuvant treatments to medication in those with moderate to severe
      depression. Pharmacotherapy is recommended for patients with moderate or severe
      depression. Tricyclic antidepressants are not effective in children and
      adolescents. Antidepressants have a boxed warning for the increased risk of
      suicide; therefore, careful assessment, follow-up, safety planning, and patient
      and family education should be included when treatment is initiated.

PMID- 22963064
TI  - Large tubular colonic mass with hematochezia and altered bowel habits. Lipoma.

PMID- 22963067
TI  - Information from your family doctor. Treating irritable bowel syndrome.

PMID- 22963065
TI  - Care of a sexually active adolescent.

PMID- 22963068
TI  - Information from your family doctor. Syphilis: what it is and how it is treated.

PMID- 22963069
TI  - Cognitive predictors of reading and math achievement among gifted referrals.
AB  - This study investigated the predictive power of the Wechsler Intelligence Scale
      for Children-Fourth Edition (WISC-IV) Full Scale IQ (FSIQ), the General Ability
      Index (GAI), and the WISC-IV index score composites on subsequent reading and
      math standardized test scores among high-achieving students. The sample consisted
      of 84 elementary-age students who received an individual cognitive assessment
      with the WISC-IV in the previous year as part of the application process for
      gifted and talented programming through their schools. Although there were no
      significant differences among the mean WISC-IV index scores, 77% of the
      individual students evidenced statistically significant WISC-IV index score
      variability. Thus, intraindividual test score variability appears to be the norm
      among high-achieving students. In spite of this variability, regression analyses
      indicated that the FSIQ predicted reading comprehension and mathematics
      achievement better than, or as well as, the GAI or individual scores for verbal
      comprehension and perceptual reasoning. None of the cognitive variables
      correlated significantly with achievement scores for Word Reading or Pseudoword
      Decoding scores, but the FSIQ, GAI, Verbal Comprehension, and Perceptual
      Reasoning scores predicted reading comprehension. Limitations and directions for
      future research are discussed.

PMID- 22963070
TI  - Examining early literacy skill differences among children in Head Start via
      latent profile analysis.
AB  - The purpose of the present study was to determine whether there are systematic
      differences in literacy skills among children from less-advantaged households,
      using latent profile analysis. Early reading skills were measured using the Early
      Arithmetic, Reading, and Learning Indicators (EARLI; DiPerna, Morgan, & Lei,
      2007) literacy tasks. Participants (N = 166) were 4-year-old children enrolled in
      Head Start. Results revealed three classifications of children: Profile 1 had the
      lowest overall literacy skill levels, with relative strength in expressive
      vocabulary and weaknesses in skills related to letter knowledge (i.e., Alphabet
      Recitation, Letter Naming); Profile 2 had the highest overall level of literacy
      skills and a relative strength on the Segmenting task; and Profile 3 showed the
      greatest variability across the EARLI probe scores, with a relative strength in
      Alphabet Recitation and weaknesses on tasks measuring phonemic and phonological
      awareness (i.e., Letter Sounds, Sound Deletion, and Segmenting). Repeated
      measures ANOVA revealed that, although students in each profile demonstrated
      skill growth over a 6-month period, significant skill differences still remained
      between profiles at the end of the preschool year.

PMID- 22963071
TI  - Steady flow analysis of mechanical cavopulmonary assistance in MRI-derived
      patient-specific fontan configurations.
AB  - This numerical study examined the performance of an intravascular axial flow
      blood pump for mechanical hemodynamic support of patients in the setting of
      Fontan failure, which presently has few treatment options. Three anatomically
      accurate geometries of the total cavopulmonary connection (TCPC) were generated
      using patients' magnetic resonance imaging data. These patient-specific
      geometries, as well as an idealized version with cylindrical vessels, were
      computationally analyzed with and without a pump in the inferior vena cava.
      Pressure flow characteristics, energy gain calculations, and blood damage
      analyses were performed for each model. The pump produced pressures of 1-14 mm Hg
      for 1500-4000 revolutions per minute, flow rates of 1-4 L/min, and pulmonary
      artery pressures of 8-24 mm Hg. Comparison of pump performance among the four
      models showed minimal intermodel differences (<5% deviation) in the pressure rise
      generated by the pump, the IVC pressure, and the energy imparted to the system by
      the pump. Blood damage analysis showed maximum fluid scalar stress values of 372
      Pa or less, and the blood damage index was less than 2% in all of the models.
      These results suggest that this axial flow blood pump performs consistently in a
      variety of TCPC vessel geometries with low risk of blood trauma.

PMID- 22963072
TI  - Possible origin of life between mica sheets: does life imitate mica?
AB  - The mica hypothesis for the origin of life proposes that life originated between
      the sheets of muscovite mica. This paper elaborates on two ways that life
      resembles what might have originated between mica sheets. First, enzymes: The
      configurations and dynamics of enzymes, with their substrates, cofactors, and
      sometimes transition metal ions, often resemble mica sheets, with their open-and
      shut motions, acting on small molecules between them, sometimes assisted by
      transition metal ions. Second, organisms: Mica world had the potential to be a
      community or ecosystem of prebiotic organisms in a way unlike other models for
      the origin of life. 

PMID- 22963073
TI  - Gail Thomson, M.D. Health Protection Agency (HPA), Porton, United Kingdom.

PMID- 22963075
TI  - Application of nanotechnology in miniaturized systems and its use in medical and
      food analysis.
AB  - A combination of Micro-Electro-Mechanical Systems and nanoscale structures allows
      for the creation of novel miniaturized devices, which broaden the boundaries of
      the diagnostic approaches. Some materials possess unique properties at the
      nanolevel, which are different from those in bulk materials. In the last years
      these properties became a focus of interest for many researchers, as well as
      methods of production, design and operation of the nanoobjects. Intensive
      research and development work resulted in numerous inventions, exploiting
      nanotechnology in miniaturized systems. Modern technical and laboratory equipment
      allows for the precise control of such devices, making them suitable for
      sensitive and accurate detection of the analytes. The current review highlights
      recent patents in the field of nanotechnology in microdevices, applicable for
      medical and food analysis. The paper covers the structural and functional basis
      of such systems and describes specific embodiments in three principal branches:
      application of nanoparticles, nanofluidics, and nanosensors in the miniaturized
      systems for advanced analytics and diagnostics.

PMID- 22963076
TI  - Nanotechnology in the development of novel functional foods or their package. An
      overview based in patent analysis.
AB  - In recent years nanotechnology has become a significant component in food
      industry. It is present in all food chain steps, from the design of new
      ingredients or additives, to the most modern systems of food quality methods or
      packaging, demonstrating the great potential of this new technology in a sector
      as traditional as food. However, while interest by industry in nanotechnology
      increases, the rejection by consumers, concerned about the potential risk, does
      too. The aim of this review is to evaluate the development of food nanotechnology
      by means of a patent analysis, highlighting current applications of
      nanotechnology along the whole food chain and contextualizing this evolution in
      the social scene.

PMID- 22963078
TI  - Evaluation of residual protein on unprocessed and decontaminated dental
      extraction forceps.
AB  - Research into protein contamination of surgical instruments has received
      increasing attention and has focused on a quantitative analysis, without
      subsequent identification of these proteins. This study aimed to validate methods
      for the isolation and identification of instrument protein contamination using
      extraction forceps as a model. The working ends of used, unclean and
      decontaminated forceps were boiled in 1% (v/v) SDS and samples precipitated using
      StrataCleanTM resin and Amicon(r) filtration. Proteins were visualised using SDS
      PAGE and identified by mass spectrometry and Western blot. A total of 17 proteins
      were identified from used, unclean forceps, including blood and bacterial
      proteins and 2 protein bands from decontaminated forceps samples which could not
      be accurately identified. The methods described, when used in conjunction with
      quantitative and surface analysis of instruments, can aid development of cleaning
      processes by identifying contaminants on used devices that have been removed
      following cleaning.

PMID- 22963077
TI  - Dietary glycemic index and glycemic load in relation to HbA1c in Japanese obese
      adults: a cross-sectional analysis of the Saku Control Obesity Program.
AB  - BACKGROUND: Dietary glycemic index or load is thought to play an important role
      in glucose metabolism. However, few studies have investigated the relation
      between glycemic index (GI) or load (GL) and glycemia in Asian populations. In
      this cross-sectional analysis of a randomized controlled trial, the Saku Control
      Obesity Program, we examined the relation between the baseline GI or GL and
      glycemia (HbA1c and fasting plasma glucose [FPG] levels), insulin resistance
      (HOMA-IR), beta-cell function (HOMA-beta), and other metabolic risk factors
      (lipid levels, diastolic and systolic blood pressure, and adiposity measures).
      METHODS: The participants were 227 obese Japanese women and men. We used multiple
      linear regression models and logistic regression models to adjust for potential
      confounding factors such as age, sex, visceral fat area, total energy intake, and
      physical activity levels. RESULTS: After adjustments for potential confounding
      factors, GI was not associated with HbA1c, but GL was positively associated with
      HbA1c. For increasing quartiles of GI, the adjusted mean HbA1c were 6.3%, 6.7%,
      6.4%, and 6.4% (P for trend = 0.991). For increasing quartiles of GL, the
      adjusted mean HbA1c were 6.2%, 6.2%, 6.6%, and 6.5% (P for trend = 0.044). In
      addition, among participants with HbA1c >= 7.0%, 20 out of 28 (71%) had a high GL
      (>= median); the adjusted odds ratio for HbA1c >= 7.0% among participants with
      higher GL was 3.1 (95% confidence interval [CI] = 1.2 to 8.1) compared to the
      participants with a lower GL (<median). Further, among 16 participants with FPG
      >= 150 mg/dL, 13 participants (81.3%) had a higher GL; the adjusted odds ratio
      for FPG >= 150 mg/dL among participants with a higher GL was 8.5 (95% confidence
      interval = 1.7 to 43.4) compared to those with a lower GL. In contrast, GI and GL
      were not associated with metabolic risk factors other than glycemia. CONCLUSIONS:
      Our findings suggest that participants with poor glycemic control tend to have a
      higher GL in an obese Japanese population.

PMID- 22963079
TI  - Brevianamides with antitubercular potential from a marine-derived isolate of
      Aspergillus versicolor.
AB  - An Aspergillus versicolor isolated from sediment collected from the Bohai Sea,
      China, yielded the new dimeric diketopiperazine brevianamide S (1), together with
      three new monomeric cometabolites, brevianamides T (2), U (3), and V (4).
      Structures were determined by detailed spectroscopic analysis. Brevianamide S
      exhibited selective antibacterial activity against Bacille Calmette-Guerin (BCG),
      suggestive of a new mechanism of action that could inform the development of next
      generation antitubercular drugs.

PMID- 22963080
TI  - A potential synbiotic product improves the lipid profile of diabetic rats.
AB  - BACKGROUND: Previous studies showed that intake of yacon or some lactic acid
      bacteria was able to inhibit the development of diabetes mellitus, by reducing
      glucose and associated symptoms, for example, the lipid profile. OBJECTIVE: The
      purpose of this study was to assess the consumption influence of a potential
      symbiotic product of soybean and yacon extract and fermented Enterococcus faecium
      CRL 183 and Lactobacillus helveticus ssp jugurti 416 in reducing blood glucose
      and lipid levels in an animal model. METHODS: Diabetes mellitus was chemically
      induced by intraperitoneal administration of streptozotocin (50 mg/kg body
      weight). The rats were divided into four groups (n=10): GI - non-diabetic animals
      that received only a standard chow diet (negative control), GII - diabetic
      animals that received only chow diet (positive control), GIII - diabetic animals
      that received the chow diet + 1 mL/kg body weight/day of soybean and yacon
      unfermented product, GIV - diabetic rats that received the chow diet + 1 mL/kg
      body weight/day of soybean and yacon fermented product. There was a seven-week
      treatment period and the following parameters were evaluated: animal body weight,
      food and water intake, blood glucose, enzyme activities of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT), triglycerides levels,
      total cholesterol, HDL-C, non-HDL-C. Cell viability of the fermented product was
      checked weekly for a seven-week period. RESULTS: The product average viable
      population was 10(8)-10(9) CFU/mL, by ensuring both the rods and cocci regular
      intake. No difference was observed between the water and feed intake and body
      weight of groups that received unfermented and fermented products and the
      untreated diabetic group. The same was observed for the blood glucose and AST and
      ALT activities, while some improvement was observed for a lipid profile,
      represented by reduction of triglycerides level by 15.07% and 33.50% in groups
      III and IV, respectively, and an increase of 23.70% in HDL-C level for group IV.
      CONCLUSION: The results showed that the ingestion of a potential symbiotic
      product was neither able to promote improvement in some of the disease symptoms,
      nor reduce blood glucose. However, a positive effect on triglycerides levels and
      HDL-cholesterol was observed in the groups that received the unfermented product
      containing yacon extract and the fermented product with Enterococcus faecium CRL
      183, as well as Lactobacillus helveticus ssp jugurti 416 and yacon extract
      (symbiotic product).

PMID- 22963081
TI  - Rheumatoid arthritis and sexuality: a patient survey in France.
AB  - BACKGROUND: The objective of this study was to evaluate the impact of rheumatoid
      arthritis (RA) on patients' sexuality and identify disease and other factors such
      as fatigue that most influence sexual relationships. METHODS: A specific
      pretested questionnaire was sent to all members of a French patient association
      (ANDAR). Questions related to demographics, disease status, quality of life
      (utility, EQ-5D), pain, psychological status (mood), fatigue and emotional and
      sexual relationships. To isolate the impact of RA, an attempt was made to include
      a matched sample from the general population. RESULTS: The analysis included 1271
      patients, but only 70 controls agreed to participate and comparisons should
      therefore be considered with caution. The two groups were similar in terms of
      age, gender distribution, living conditions and diseases other than RA. However,
      patients scored worse for global health, mood, fatigue, had a lower utility (0.55
      versus 0.65). Controls were more active sexually (69% versus 63%), in particular
      women (71% versus 60%). Age, gender, living alone, physical function and mood
      were significant predictors for being sexually active for patients; for controls,
      age and overall quality of life (utility) were significant predictors.
      CONCLUSIONS: While it is known that RA has a negative impact on patients'
      sexuality, there have been few attempts to quantify the problem. Our study
      highlights the negative impact of RA on patients' sexuality, and triggers the
      question how to include this aspect into care.

PMID- 22963082
TI  - Detection of human herpesvirus 8 by quantitative polymerase chain reaction:
      development and standardisation of methods.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's
      sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion
      lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of
      South-east Asia and Oceania. While the treatment of external KS lesions can be
      monitored by clinical observation, the internal lesions of KS, MCD and PEL
      require extensive and expensive internal imaging, or autopsy. In patients with
      MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months.
      HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available
      in many parts of the world, including those with high prevalence of KS and HHV-8.
      METHODS: A new molecular facility with stringent three-phase workflow was
      established, adhering to NPAAC and CLSI guidelines. Three fully validated
      quantitative assays were developed: two for detection and quantification of HHV
      8; one for GAPDH, necessary for normalisation of viral loads in tissue and
      peripheral blood. RESULTS: The HHV-8 ORF73 and ORF26 qPCR assays were 100%
      specific. All qPCR assays, displayed a broad dynamic range (102 to 1010
      copies/MUL TE Buffer) with a limit of detection of 4.85x103, 5.61x102, and
      2.59x102 copies/MUL TE Buffer and a limit of quantification of 4.85x103,
      3.01x102, and 1.38x102 copies/MUL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and
      GAPDH respectively.The assays were tested on a panel of 35 KS biopsies from
      Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV
      8 copies/MUL DNA extract (range: 4.37x103 to 1.47x106 copies/MUL DNA extract):
      When normalised these equate to an average viral load of 2.44x104 HHV-8
      copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells).
      CONCLUSIONS: These are the first fully optimised, validated and MIQE compliant
      HHV-8 qPCR assays established in Australia. They worked well for qualitative
      detection of HHV-8 in archival tissue, and are well-suited for quantitative
      detection in whole blood. They are now available for research, for clinical
      diagnosis of HHV-8 infection, and for monitoring treatment efficacy.

PMID- 22963083
TI  - The association between p3 amplitude at age 11 and criminal offending at age 23.
AB  - Reduced P3 amplitude to targets is an information-processing deficit associated
      with adult antisocial behavior and may reflect dysfunction of the temporal
      parietal junction. This study aims to examine whether this deficit precedes
      criminal offending. From a birth cohort of 1,795 children, 73 individuals who
      become criminal offenders at age 23 and 123 noncriminal individuals were assessed
      on P3 amplitude. The two groups did not differ on gender, ethnicity, and social
      adversity. P3 amplitude was measured over the temporal-parietal junction during a
      visual continuous performance task at age 11, together with antisocial behavior.
      Criminal convictions were assessed at age 23. Reduced P3 amplitude at age 11 was
      associated with increased antisocial behavior at age 11. Criminal offenders
      showed significantly reduced P3 amplitudes to target stimuli compared to
      controls. Findings remained significant after controlling for antisocial behavior
      and hyperactivity at age 11 and alcoholism at age 23. P3 deficits at age 11 are
      associated with adult crime at age 23, suggesting that reduced P3 may be an early
      neurobiological marker for cognitive and affective processes subserved by the
      temporal-parietal junction that place a child at risk for adult crime.

PMID- 22963085
TI  - Cutaneous findings in children with intellectual disabilities.
AB  - The link between pediatric dermatology and intellectual disabilities (ID) is
      revised, according to the author's personal experience and the existing published
      work. Cutaneous manifestations in children with ID can be: (i) a key element to
      reach a diagnosis, as in neurodermatoses; (ii) a peculiar sign to define a
      complex syndrome; (iii) linked to behavioral features; (iv) iatrogenic, caused by
      drugs, as a side-effect; and (v) independent from ID.

PMID- 22963084
TI  - Widespread and persistent invasions of terrestrial habitats coincident with
      larval feeding behavior transitions during snail-killing fly evolution (Diptera:
      Sciomyzidae).
AB  - BACKGROUND: Transitions in habitats and feeding behaviors were fundamental to the
      diversification of life on Earth. There is ongoing debate regarding the typical
      directionality of transitions between aquatic and terrestrial habitats and the
      mechanisms responsible for the preponderance of terrestrial to aquatic
      transitions. Snail-killing flies (Diptera: Sciomyzidae) represent an excellent
      model system to study such transitions because their larvae display a range of
      feeding behaviors, being predators, parasitoids or saprophages of a variety of
      mollusks in freshwater, shoreline and dry terrestrial habitats. The remarkable
      genus Tetanocera (Tetanocerini) occupies five larval feeding groups and all of
      the habitat types mentioned above. This study has four principal objectives: (i)
      construct a robust estimate of phylogeny for Tetanocera and Tetanocerini, (ii)
      estimate the evolutionary transitions in larval feeding behaviors and habitats,
      (iii) test the monophyly of feeding groups and (iv) identify mechanisms
      underlying sciomyzid habitat and feeding behavior evolution. RESULTS: Bayesian
      inference and maximum likelihood analyses of molecular data provided strong
      support that the Sciomyzini, Tetanocerini and Tetanocera are monophyletic.
      However, the monophyly of many behavioral groupings was rejected via phylogenetic
      constraint analyses. We determined that (i) the ancestral sciomyzid lineage was
      terrestrial, (ii) there was a single terrestrial to aquatic habitat transition
      early in the evolution of the Tetanocerini and (iii) there were at least 10
      independent aquatic to terrestrial habitat transitions and at least 15 feeding
      behavior transitions during tetanocerine phylogenesis. The ancestor of Tetanocera
      was aquatic with five lineages making independent transitions to terrestrial
      habitats and seven making independent transitions in feeding behaviors.
      CONCLUSIONS: The preponderance of aquatic to terrestrial transitions in
      sciomyzids goes against the trend generally observed across eukaryotes. Damp
      shoreline habitats are likely transitional where larvae can change habitat but
      still have similar prey available. Transitioning from aquatic to terrestrial
      habitats is likely easier than the reverse for sciomyzids because morphological
      characters associated with air-breathing while under the water's surface are lost
      rather than gained, and sciomyzids originated and diversified during a general
      drying period in Earth's history. Our results imply that any animal lineage
      having aquatic and terrestrial members, respiring the same way in both habitats
      and having the same type of food available in both habitats could show a similar
      pattern of multiple independent habitat transitions coincident with changes in
      behavioral and morphological traits.

PMID- 22963086
TI  - The intestinal microbial diversity in mud crab (Scylla paramamosain) as
      determined by PCR-DGGE and clone library analysis.
AB  - AIMS: To identify the intestinal microbial diversity in mud crab and to
      investigate the bacterial difference in the intestinal microbiology between wild
      crabs (WC), pond-raised healthy and diseased crabs (DC). METHODS AND RESULTS: The
      intestinal microbial community of mud crab Scylla paramamosain from WC, pond
      raised healthy crabs (HC) and DC were examined by Denaturing Gradient Gel
      Electrophoresis (DGGE) and clone library analysis of 16S rDNA gene. Eight of 21
      representative DGGE bands were affiliated with unidentified or unclassified
      bacteria. Vibrio, Pseudoalteromonas and Shewanella were also found from the DGGE
      gel. Analysis of clone libraries revealed that all sequenced clones were grouped
      into either of the following phyla: Proteobacteria, Firmicutes, Tenericutes,
      Bacteroidetes, Fusobacteria, Cyanobacteria and unidentified or unclassified
      bacteria. The phylotypes affiliated with Firmicutes were not found in DC library,
      yet DC had a little portion of Cyanobacteria which did not exist in both WC and
      HC library. Real-time PCR showed that the abundance of the total bacterial load
      in WC were significantly three times higher than that in healthy and DC, the
      abundance of Bacteriodes in healthy and WC were as much four times, three times
      as that in DC, respectively. CONCLUSIONS: Statistical analysis showed that the
      bacterial communities in intestine of the mud crab from these three populations
      were significantly different. The phylotypes of the Bacteriodes and Tenericutes
      were the dominant population in the gut of the mud crab. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study demonstrated significant differences in the intestinal
      bacterial composition of three crab populations. This knowledge will increase our
      understanding of the effect of growth conditions on bacterial community
      composition in the crab gut and provide necessary data for further development of
      probiotic products for diseases prevention in crab farming.

PMID- 22963088
TI  - Electronic transitions of iridium monoxide: ground and low-lying electronic
      states.
AB  - The electronic transition spectrum of IrO in the spectral region between 448 and
      650 nm has been recorded and analyzed using laser vaporization/reaction free jet
      expansion and laser induced fluorescence spectroscopy. The IrO molecule was
      produced by reacting laser-ablated iridium atoms with N(2)O seeded in argon. Five
      electronic transition systems, namely, the [17.6]2.5 - X(2)Delta(5/2), [17.8]2.5 
      X(2)Delta(5/2), [21.5]2.5 - X(2)Delta(5/2), [22.0]2.5 - X(2)Delta(5/2), and
      [21.9]3.5 - Omega = 3.5 systems were identified. Transition lines of both the
      (191)IrO and (193)IrO isotopes were observed and analyzed. IrO was determined to
      have a X(2)Delta(5/2) ground state. A least squares fit of the measured
      rotational lines yielded molecular constants for the ground and low-lying
      electronic states. A molecular orbital energy level diagram has been used to help
      with the assignment of the observed electronic states.

PMID- 22963087
TI  - Enhanced anti-influenza agents conjugated with anti-inflammatory activity.
AB  - Influenza therapy with a single targeted compound is often limited in efficacy
      due to the rapidly developed drug resistance. Moreover, the uncontrolled virus
      induced cytokines could cause the high mortality of human infected by H5N1 avian
      influenza virus. In this study, we explored the novel dual-targeted bifunctional
      anti-influenza drugs formed by conjugation with anti-inflammatory agents. In
      particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1)
      and ZA-7-CA-amide (7) showed simultaneous inhibition of influenza virus
      neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates
      provided remarkable protection of cells and mice against influenza infections.
      Intranasal administration of low dosage (<1.2 MUmol/kg/day) of ZA conjugates
      exhibited much greater effect than the combination therapy with ZA and the anti
      inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1
      influenza viruses.

PMID- 22963089
TI  - Feeling good and bad about the past and future self.
AB  - Prior research has shown that memories of feeling good about the self often focus
      on achievement themes, whereas memories of feeling bad about the self often focus
      on interpersonal themes. This study examined whether a similar relationship would
      be evident for imagined future events. Young adults in the United States and
      Denmark provided memories and imagined future events that are associated with
      positive or negative self-regard. Across cultures, achievement themes were
      prominently represented in memories of positive self-regard and interpersonal
      themes were prominently represented in memories of negative self-regard. In
      contrast, relationships between the emotional valence and thematic content of
      imagined future events were weak and inconsistent. Our results raise new
      questions for the theory that imagined future episodes are constructed primarily
      from recombinations of past episodes.

PMID- 22963090
TI  - "Tell me about yourself".

PMID- 22963091
TI  - Nurse practitioners as valuable partners.

PMID- 22963092
TI  - Effects of inclusive leadership.

PMID- 22963093
TI  - More app suggestions for family physicians, from family physicians.

PMID- 22963094
TI  - More app suggestions for family physicians, from family physicians.

PMID- 22963095
TI  - More app suggestions for family physicians, from family physicians.

PMID- 22963096
TI  - Evaluating employment agreements.

PMID- 22963097
TI  - Documenting and coding preventive visits: a physicians's perspective.

PMID- 22963098
TI  - Rethinking the difficult patient encounter.

PMID- 22963099
TI  - How to reduce your malpractice risk.

PMID- 22963100
TI  - The anatomy of an ICD-10 code.

PMID- 22963109
TI  - A family physician's legacy.

PMID- 22963110
TI  - A rare case of permanent junctional reciprocating tachycardia ablated on the roof
      of the left atrium.
AB  - Left-sided anteroseptal accessory pathways that course through the aortomitral
      fibrous continuity are some of the rarest types of accessory pathways. At this
      region the atrium and ventricle are separated by their greatest distance because
      of the intervening aortic valve. These pathways often have a long circuitous
      course that may involve the root and cusps of the aortic valve. Prior reports
      have demonstrated the feasibility of ablating these pathways along the
      anteroseptal mitral annulus, the left ventricular outflow tract, or in the left
      or noncoronary cusps of the aortic valve. We describe a case of a concealed
      decremental anteroseptal accessory pathway that was ablated on the roof of the
      left atrium remote from the mitral or aortic valve annuli. This report indicates
      that when an appropriate site for ablation of a left-sided anteroseptal accessory
      pathway is not found close to a valve annulus, these pathways may be amenable to
      ablation by targeting their atrial insertion site.

PMID- 22963111
TI  - Field-induced slow magnetic relaxation in a six-coordinate mononuclear cobalt(II)
      complex with a positive anisotropy.
AB  - The novel mononuclear Co(II) complex cis-[Co(II)(dmphen)(2)(NCS)(2)].0.25EtOH (1)
      (dmphen = 2,9-dimethyl-1,10-phenanthroline) features a highly rhombically
      distorted octahedral environment that is responsible for the strong positive
      axial and rhombic magnetic anisotropy of the high-spin Co(II) ion (D = +98 cm(-1)
      and E = +8.4 cm(-1)). Slow magnetic relaxation effects were observed for 1 in the
      presence of a dc magnetic field, constituting the first example of field-induced
      single-molecule magnet behavior in a mononuclear six-coordinate Co(II) complex
      with a transverse anisotropy energy barrier.

PMID- 22963113
TI  - Toric implantable collamer lens for high myopic astigmatism in keratoconic
      patients after six months.
AB  - BACKGROUND: The aim was to evaluate the safety, efficacy, stability and
      predictability of posterior chamber collagen copolymer phakic intraocular lens
      (pIOL) implantation to correct myopia and myopic astigmatism associated with
      keratoconus. METHODS: The unaided vision and visual acuity, refraction and
      adverse events were measured in 22 keratoconic eyes of 14 patients after using an
      implantable collamer lens (ICL) (STAAR Surgical Inc.) to correct refractive
      error. The outcome was evaluated over six months. RESULTS: The mean pre-operative
      spherical equivalent (SE) and cylinder changed from -4.98 +/- 2.63 DS and -2.77
      +/- 0.99 DC to -0.33 +/- 0.51 DS and -1.23 +/- 0.65 DC, respectively at the end
      of six months. Before the surgery the mean Snellen decimal visual acuity was 0.63
      +/- 0.20. The mean unaided vision and visual acuity changed to 0.76 +/- 0.23 and
      0.85 +/- 0.21, respectively at the end of six months. The mean safety and
      efficacy indices were 1.40 +/- 0.32 and 1.24 +/- 0.34, respectively. No eye lost
      a line of visual acuity and 17 eyes (77.3 per cent) gained one or more lines.
      Fifteen eyes (68.2 per cent) were within 0.50 D and 20 (90.9 per cent) were
      within 1.00 D of the desired spherical equivalent refraction. There was a change
      in manifest refraction of 0.09 +/- 0.21 (ranging from -0.25 to +0.75) from one
      week to six months after the surgery. CONCLUSION: The clinical outcomes of the
      current study demonstrate the safety, efficacy and predictability of toric
      implantable collamer lens in the correction of myopia and myopic astigmatism
      associated with keratoconus. The patients' refractions achieved early stability
      and remained stable during the course of the study.

PMID- 22963112
TI  - Midbrain raphe stimulation improves behavioral and anatomical recovery from fluid
      percussion brain injury.
AB  - The midbrain median raphe (MR) and dorsal raphe (DR) nuclei were tested for their
      capacity to regulate recovery from traumatic brain injury (TBI). An implanted,
      wireless self-powered stimulator delivered intermittent 8-Hz pulse trains for 7
      days to the rat's MR or DR, beginning 4-6 h after a moderate parasagittal (right)
      fluid-percussion injury. MR stimulation was also examined with a higher frequency
      (24 Hz) or a delayed start (7 days after injury). Controls had sham injuries,
      inactive stimulators, or both. The stimulation caused no apparent acute responses
      or adverse long-term changes. In water-maze trials conducted 5 weeks post-injury,
      early 8-Hz MR and DR stimulation restored the rate of acquisition of reference
      memory for a hidden platform of fixed location. Short-term spatial working
      memory, for a variably located hidden platform, was restored only by early 8-Hz
      MR stimulation. All stimulation protocols reversed injury-induced asymmetry of
      spontaneous forelimb reaching movements tested 6 weeks post-injury. Post-mortem
      histological measurement at 8 weeks post-injury revealed volume losses in
      parietal-occipital cortex and decussating white matter (corpus callosum plus
      external capsule), but not hippocampus. The cortical losses were significantly
      reversed by early 8-Hz MR and DR stimulation, the white matter losses by all
      forms of MR stimulation. The generally most effective protocol, 8-Hz MR
      stimulation, was tested 3 days post-injury for its acute effect on forebrain
      cyclic adenosine monophosphate (cAMP), a key trophic signaling molecule. This
      procedure reversed injury-induced declines of cAMP levels in both cortex and
      hippocampus. In conclusion, midbrain raphe nuclei can enduringly enhance recovery
      from early disseminated TBI, possibly in part through increased signaling by cAMP
      in efferent targets. A neurosurgical treatment for TBI using interim electrical
      stimulation in raphe repair centers is suggested.

PMID- 22963115
TI  - Long-term care in Asia.

PMID- 22963116
TI  - Long-term care in China: issues and prospects.
AB  - One of the major socioeconomic challenges China faces is the rapid aging of its
      population. China is now an aging society, even though it is still regarded as a
      middle-income economy. Coupled with the market-driven reform of social services
      and rapid erosion of family support, the provision of affordable and accessible
      social care services to older people has already become an urgent issue for the
      government to address. Looking into the future, the formulation of a sustainable
      position on long-term care (LTC) will increasingly become the major focus of
      social policy. This article sets out the background to the demographic shifts
      resulting in the emerging need for LTC in China. It analyzes the issues facing
      LTC services and reviews their prospects, including the structure, operation,
      financing, and interfacing of residential and community-based home care services.

PMID- 22963114
TI  - Venous thromboembolism risk in relation to use of different types of
      postmenopausal hormone therapy in a large prospective study.
AB  - BACKGROUND: Current use of menopausal hormone therapy (HT) increases the risk of
      venous thromboembolism (VTE) and the formulations used may affect risk. METHODS:
      A total of 1,058,259 postmenopausal UK women were followed by record linkage to
      routinely collected National Health Service hospital admission and death records.
      HT use and risk of VTE was examined using Cox regression to estimate relative
      risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 3.3 million years
      of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years
      after last reporting HT use. RRs in current vs. never users at last reporting
      varied by HT formulation: the risk was significantly greater for oral estrogen
      progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42
      [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82
      [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by
      progestin type, with significantly greater risks for preparations containing
      medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91
      [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting
      had twice the risk of VTE in the first 2 years after starting HT than later
      (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis
      with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT
      were admitted to hospital for (or died from) pulmonary embolism, compared with 1
      in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen
      progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen
      progestin HT containing medroxyprogesterone acetate. CONCLUSIONS: The risk of VTE
      varied considerably by HT formulation, being greatest in users of oral estrogen
      progestin HT, especially formulations containing medroxyprogesterone acetate.

PMID- 22963117
TI  - Social exclusion and neighborhood support: a case study of empty-nest elderly in
      urban Shanghai.
AB  - The phenomenon of empty-nest elderly (ENE) has become a significant social issue
      in China. In this research on ENEs in urban Shanghai, a coastal city in China,
      case studies were undertaken through in-depth semistructured interviews to
      examine the social exclusion risks ENEs may face and the influence of
      neighborhood support on such risks. The results show 5 aspects of social
      exclusion ENEs are experiencing. Moreover, the neighborhood has the potential for
      providing different forms of support to reduce social exclusion risks. The
      research and service implications of our findings for promoting the holistic well
      being of ENEs in China are discussed.

PMID- 22963118
TI  - Elderly Chinese and their family caregivers' perceptions of good care: a
      qualitative study in Shandong, China.
AB  - This study aims to understand what older Chinese people with chronic illness and
      their family caregivers perceive to be good care, and to compare perspectives of
      those living in rural and urban areas. We conducted semistructured interviews
      with 24 care recipients and 23 caregivers in Shandong, China. Two major themes
      were identified: (a) filial piety as the standard, and (b) modifying cultural
      ideals to meet reality. There was overall consistency in perceptions of study
      participants. Variations between rural and urban elders' perceptions appear to
      reflect differences in socioeconomic development and institutional structures.

PMID- 22963119
TI  - An evaluation study of a dementia screening program in Taiwan: an application of
      the theory of planned behaviors.
AB  - A challenge facing dementia service providers is how to detect dementia early to
      facilitate timely intervention. This article reports findings of an evaluation
      study of a dementia-screening program in Taiwan utilizing the Theory of Planned
      Behaviors. We present the Short Portable Mental Status Questionnaire (SPMSQ)
      program rationale and examine the effects of this important health and social
      service intervention. Follow-up telephone interviews were completed by 108
      respondents. Findings indicate that the SPMSQ program was successful in
      identifying suspected dementia. Results also show that the dementia-screening
      program contributed to an increase in medical service utilization and in unpaid
      informal care.

PMID- 22963120
TI  - "Many Helping Hands": a review and analysis of long-term care policies, programs,
      and practices in Singapore.
AB  - Using the political economy perspective to examine key long-term care policies
      and provisions, we uncover some ideological underpinnings of policy-making in
      Singapore. Family involvement, an inherent part of the long-term care system, is
      overtly reinforced by legislations and policy imperatives. Further, the
      government encourages and expects the participation of nonstate actors in the
      provision of services as part of its Many Helping Hands approach to welfare
      provision. In our analysis, we argue that the government's emphasis of certain
      ideology, such as self-reliance and cultural exceptionalism, allows it to adopt a
      residual and philanthropic approach in support of its macro-economic and
      legitimacy concerns.

PMID- 22963121
TI  - Balancing long-term care in Japan.
AB  - This article discusses Japan's long-term care (LTC) from the perspective of
      balancing the provision and financing of care. Specifically, this article
      provides an overview of the long-term care insurance (LTCI) system in Japan and
      analyzes the current state of Japan's LTC with current statistical data as to
      whether the supply meets the demand for care by frail elders and their families.

PMID- 22963123
TI  - Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in
      light touch cutaneous mechanoreceptors.
AB  - BACKGROUND: Sickle cell disease (SCD) is associated with both acute vaso
      occlusive painful events as well as chronic pain syndromes, including heightened
      sensitivity to touch. We have previously shown that mice with severe SCD (HbSS
      mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have
      sensitized nociceptors, which contribute to increased mechanical sensitivity.
      Yet, the hypersensitivity in these neural populations alone may not fully explain
      the mechanical allodynia phenotype in mouse and humans. FINDINGS: Using the Light
      Touch Behavioral Assay, we found HbSS mice exhibited increased responses to
      repeated application of both innocuous punctate and dynamic force compared to
      control HbAA mice (100% normal human hemoglobin). HbSS mice exhibited a 2-fold
      increase in percent response to a 0.7mN von Frey monofilament when compared to
      control HbAA mice. Moreover, HbSS mice exhibited a 1.7-fold increase in percent
      response to the dynamic light touch "puffed" cotton swab stimulus. We further
      investigated the mechanisms that drive this behavioral phenotype by focusing on
      the cutaneous sensory neurons that primarily transduce innocuous, light touch.
      Low threshold cutaneous afferents from HbSS mice exhibited sensitization to
      mechanical stimuli that manifested as an increase in the number of evoked action
      potentials to suprathreshold force. Rapidly adapting (RA) Abeta and Adelta D-hair
      fibers showed the greatest sensitization, each with a 75% increase in
      suprathreshold firing compared to controls. Slowly adapting (SA) Abeta afferents
      had a 25% increase in suprathreshold firing compared to HbAA controls.
      CONCLUSIONS: These novel findings demonstrate mice with severe SCD exhibit
      mechanical allodynia to both punctate and dynamic light touch and suggest that
      this behavioral phenotype may be mediated in part by the sensitization of light
      touch cutaneous afferent fibers to suprathreshold force. These findings indicate
      that Abeta fibers can be sensitized to mechanical force and should potentially be
      examined for sensitization in other tissue injury and disease models.

PMID- 22963124
TI  - Physiological controller of an intra-aorta pump based on baroreflex sensitivity.
AB  - Left ventricular assist devices are increasingly used for long-term support in
      heart failure patients. It is important to find an optimum operating point for
      the pump that is appropriate for the existing function of the heart and the state
      of the circulatory system. Therefore, baroreflex sensitivity (BRS), as an
      indicator of heart function, is chosen as the control variable. In order to find
      an optimum point automatically, an extremum search algorithm (ESA) is designed to
      find an optimal mean arterial pressure (MAP), for which the BRS is maximum. Then,
      a MAP controller based on model-free adaptive control is designed to ensure that
      the measured MAP tracks the desired one. In order to test the feasibility of the
      control strategy, numerical simulations and simplified in vitro experiments were
      conducted. A mathematic model of the cardiovascular system simulating left
      ventricular failure, physical activity, and recovery of cardiac function is used
      in the simulation. The numerical simulations show that the maximum value of BRS
      can be found automatically by using ESA. The rotational speed of the pump is
      automatically increased (from 6500 rpm to 7000 rpm), and peripheral resistance is
      decreased to simulate slight physical activity. When E(max) is increased from 0.6
      mm Hg/mL to 1.8 mm Hg/mL to mimic heart recovery, the speed is decreased from
      7000 rpm to 6300 rpm in response. The optimum operating point for the pump can be
      detected by the proposed control strategy without the need to set a reference
      value for the control variable by operators.

PMID- 22963125
TI  - In vitro actinomycete biofilm development and inhibition by the polyene
      antibiotic, nystatin, on IUD copper surfaces.
AB  - The presence of intrauterine contraceptive devices (IUDs) gives a solid surface
      for attachment and an ideal niche for biofilm to form and flourish. Pelvic
      actinomycosis is often associated with the use of IUDs. Treatment of IUD
      associated pelvic actinomycosis requires the immediate removal of the IUD.
      Therefore, this article presents in vitro evidence to support the use of novel
      antibiotics in the treatment of actinomycete biofilms. Twenty one clinical
      actinomycetes isolates from endocervical swabs of IUD wearers were assessed for
      their biofilm forming ability. An in vitro biofilm model with three isolates,
      Streptomyces strain A4, Nocardia strain C15 and Nocardia strain C17 was subjected
      to treatment with nystatin. Inhibition of biofilm formation by nystatin was found
      to be concentration dependent, with MBIC50 values in the range 0.08-0.16 mg ml(
      1). Furthermore, at a concentration of 0.16 mg ml(-1), nystatin inhibited the
      twitching motility of the isolates, providing evidence for a possible mechanism
      of biofilm inhibition.

PMID- 22963126
TI  - Largely pi-extended thienoacenes with internal thieno[3,2-b]thiophene
      substructures: synthesis, characterization, and organic field-effect transistor
      applications.
AB  - Two largely pi-extended thienoacenes with internal thieno[3,2-b]thiophene
      substructures, i.e., bis[1]benzothieno[2,3-d;2',3'-d']benzo[1,2-b;4,5
      b']dithiophene (BBTBDT) and bis(naphtho[2,3-b]thieno)[2,3-d;2',3'-d']benzo[1,2
      b;4,5-b']dithiophene (BNTBDT), were synthesized, characterized, and evaluated as
      an active layer in thin-film organic field-effect transistors.

PMID- 22963127
TI  - Denitrification potential in stormwater control structures and natural riparian
      zones in an urban landscape.
AB  - Humans have significantly altered urban landscapes, creating impervious surfaces,
      and changing drainage patterns that increase volume and velocity as well as
      frequency and timing of runoff following precipitation events. These changes in
      runoff have impaired streams and riparian areas that previously reduced watershed
      nitrogen (N) flux through uptake and denitrification. Stormwater control measures
      (SCM) are used most frequently to mitigate these hydrologic impacts. While SCM
      control runoff, their ability to remove N compared to natural riparian areas is
      not well-known. In this study we compared potential denitrification [as
      denitrification enzyme activity (DEA)] in five types of SCM (wet ponds, dry
      detention ponds, dry extended detention, infiltration basin, and filtering
      practices) and forested and herbaceous riparian areas in Baltimore, MD. DEA was
      higher in SCM (1.2 mg N kg(-1) hr(-1)) than in riparian areas (0.4 mg N kg(-1)
      hr(-1)). While DEA was highly correlated with soil moisture, organic matter,
      microbial biomass, and soil respiration areas across sites, it was always higher
      in SCM at equivalent levels of these variables. SCM appear to function as
      denitrification hotspots and, despite having similar microbial biomass, have
      higher potential denitrification than natural riparian areas.

PMID- 22963128
TI  - Adherence to medication in patients with psoriasis: a systematic literature
      review.
AB  - Psoriasis is associated with considerable physical and psychological morbidity.
      Optimal use of psoriasis treatments can limit the physical manifestations of
      psoriasis and help improve quality of life, but nonadherence is common. Smoking,
      obesity and excessive alcohol consumption are prevalent in this population. A
      systematic review of adherence to medication and recommendations for lifestyle
      change in psoriasis was undertaken, with a critical appraisal of the quality of
      the selected studies. Electronic searches from inception to March 2012 (PubMed,
      Web of Science and Embase) were conducted. Twenty-nine studies were included;
      however, none examined adherence to advice about lifestyle change. Studies using
      a dichotomous classification of adherence tended to report suboptimal adherence,
      with 21.6-66.6% of patients classed as adherent. No consistent pattern of results
      emerged for sociodemographical, disease and lifestyle factors as determinants of
      adherence. However, some treatment factors were associated with adherence. While
      mixed findings were reported for quality of life as a determinant of adherence,
      psychological factors (psychological distress and patient satisfaction with care
      and therapy) were associated with adherence. Only tentative conclusions can be
      made for determinants of adherence because the methodological quality of many of
      the included studies limits conclusions. There is a need for improved quality of
      research and reporting in this area, and this review provides a platform from
      which future research within this area should progress, along with suggested
      research recommendations.

PMID- 22963129
TI  - Bone marrow-derived cells can acquire renal stem cells properties and ameliorate
      ischemia-reperfusion induced acute renal injury.
AB  - BACKGROUND: Bone marrow (BM) stem cells have been reported to contribute to
      tissue repair after kidney injury model. However, there is no direct evidence so
      far that BM cells can trans-differentiate into renal stem cells. METHODS: To
      investigate whether BM stem cells contribute to repopulate the renal stem cell
      pool, we transplanted BM cells from transgenic mice, expressing enhanced green
      fluorescent protein (EGFP) into wild-type irradiated recipients. Following
      hematological reconstitution and ischemia-reperfusion (I/R), Sca-1 and c-Kit
      positive renal stem cells in kidney were evaluated by immunostaining and flow
      cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF) was
      administrated to further explore if G-CSF can mobilize BM cells and enhance trans
      differentiation efficiency of BM cells into renal stem cells. RESULTS: BM-derived
      cells can contribute to the Sca-1(+) or c-Kit(+) renal progenitor cells
      population, although most renal stem cells came from indigenous cells.
      Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM
      derived renal stem cells and increased capillary density of I/R injured kidneys.
      CONCLUSIONS: These findings indicate that BM derived stem cells can give rise to
      cells that share properties of renal resident stem cell. Moreover, G-CSF
      mobilization can enhance this effect.

PMID- 22963130
TI  - Pulmonary TCR gammadelta T cells induce the early inflammation of granuloma
      formation by a glycolipid trehalose 6,6'-dimycolate (TDM) isolated from
      Mycobacterium tuberculosis.
AB  - We previously showed that formation of pulmonary granulomas in mice in response
      to a mycobacterial glycolipid, trehalose 6,6'-dimycolate (TDM) is due to the
      action of TNF-alpha and not of IFN-gamma. However, the mechanisms of formation
      and maintenance of pulmonary granulomas are not yet clear. The purpose of the
      present study is to evaluate the mechanisms of granuloma formation by TDM at the
      early phase. Histological analysis showed that inflammatory cells infiltrated the
      murine pulmonary interstitium on day 2 after an intravenous injection with TDM as
      a w/o/w emulsion. Clear granuloma formation was observed on day 7 after the
      injection. The mRNA expression of IL-17, IFN-gamma and macrophage inflammatory
      protein 2 was found in lung mononuclear cells at the day after TDM injection. The
      major IL-17-producing cells were T-cell receptor (TCR) gammadelta T cells
      expressing Vgamma6. In mice depleted of gammadelta T cells by treatment with anti
      TCR gammadelta monoclonal antibody, the number of TDM-induced granuloma was
      decreased, but the size of granuloma was not affected. Our results suggest that
      the mycobacterial glycolipid TDM causes activation of IL-17-producing TCR
      gammadelta T cells and stimulates chemotaxis of inflammatory cells including
      neutrophils in to lung.

PMID- 22963131
TI  - Estimating quality adjusted progression free survival of first-line treatments
      for EGFR mutation positive non small cell lung cancer patients in The
      Netherlands.
AB  - BACKGROUND: Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in
      advanced non-small cell lung cancer (NSCLC) patients with an activating mutation
      in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed
      a benefit in progression free survival for gefitinib versus doublet chemotherapy
      regimens in patients with an activated EGFR mutation (EGFR M+). From a patient
      perspective, progression free survival is important, but so is health-related
      quality of life. Therefore, this analysis evaluates the Quality Adjusted
      progression free survival of gefitinib versus three relevant doublet
      chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis);
      paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients
      with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival
      rather than overall survival for its time frame in order to better compare the
      treatments and to account for the influence that subsequent treatment lines would
      have on overall survival analysis. METHODS: Mean progression free survival for
      Pac/Carb was obtained by extrapolating the median progression free survival as
      reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis
      was used to estimate the mean progression free survival for therapies of interest
      relative to Pac/Carb. Adjustment for health-related quality of life was done by
      incorporating utilities for the Dutch population, obtained by converting FACT-L
      data (from IPASS) to utility values and multiplying these with the mean
      progression free survival for each treatment arm to determine the Quality
      Adjusted progression free survival. Probabilistic sensitivity analysis was
      carried out to determine 95% credibility intervals. RESULTS: The Quality Adjusted
      progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months
      (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5)
      for Pac/Carb and 8.3 (7.0; 9.9) for gefitinib. CONCLUSIONS: In the Dutch health
      care setting, the previously established progression free survival benefit of
      first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to standard
      doublet chemotherapy is further supported by the Quality Adjusted PFS, which
      takes into account the additional health-related quality of life benefits of
      gefitinib over doublet chemotherapy.

PMID- 22963133
TI  - Arthrobotrys oligospora-mediated biological control of diseases of tomato
      (Lycopersicon esculentum Mill.) caused by Meloidogyne incognita and Rhizoctonia
      solani.
AB  - AIMS: To study the biocontrol potential of nematode-trapping fungus Arthrobotrys
      oligospora in protecting tomato (Lycopersicon esculentum Mill.) against
      Meloidogyne incognita and Rhizoctonia solani under greenhouse and field
      conditions. METHODS AND RESULTS: Five isolates of the nematode-trapping fungus
      Arthrobotrys oligospora isolated from different parts of India were tested
      against Meloidogyne incognita and Rhizoctonia solani in tomato (Lycopersicon
      esculentum Mill.) plants grown under greenhouse and field conditions.
      Arthrobotrys oligospora-treated plants showed enhanced growth in terms of shoot
      and root length and biomass, chlorophyll and total phenolic content and high
      phenylalanine ammonia lyase activity in comparison with M. incognita- and R.
      solani-inoculated plants. Biochemical profiling when correlated with disease
      severity and intensity in A. oligospora-treated and untreated plants indicate
      that A. oligospora VNS-1 offered significant disease reduction in terms of number
      of root galls, seedling mortality, lesion length, disease index, better plant
      growth and fruit yield as compared to M. incognita- and R. solani-challenged
      plants. CONCLUSION: The result established that A. oligospora VNS-1 has the
      potential to provide bioprotection agents against M. incognita and R. solani.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Arthrobotrys oligospora can be a better
      environment friendly option and can be incorporated in the integrated disease
      management module of crop protection. Application of A. oligospora not only helps
      in the control of nematodes but also increases plant growth and enhances
      nutritional value of tomato fruits. Thus, it proves to be an excellent biocontrol
      as well as plant growth promoting agent.

PMID- 22963132
TI  - Miocene and Pliocene dominated diversification of the lichen-forming fungal genus
      Melanohalea (Parmeliaceae, Ascomycota) and Pleistocene population expansions.
AB  - BACKGROUND: Factors promoting diversification in lichen symbioses remain largely
      unexplored. While Pleistocene events have been important for driving
      diversification and affecting distributions in many groups, recent estimates
      suggest that major radiations within some genera in the largest clade of
      macrolichens (Parmeliaceae, Ascomycota) vastly predate the Pleistocene. To better
      understand the temporal placement and sequence of diversification events in
      lichens, we estimated divergence times in a common lichen-forming fungal genus,
      Melanohalea, in the Northern Hemisphere. Divergence times were estimated using
      both concatenated gene tree and coalescent-based multilocus species tree
      approaches to assess the temporal context of major radiation events within
      Melanohalea. In order to complement our understanding of processes impacting
      genetic differentiation, we also evaluated the effects of Pleistocene glacial
      cycles on population demographics of distinct Melanohalea lineages, differing in
      reproductive strategies. RESULTS: We found that divergence estimates, from both
      concatenated gene tree and coalescent-based multilocus species tree approaches,
      suggest that diversification within Melanohalea occurred predominantly during the
      Miocene and Pliocene, although estimated of divergence times differed by up to
      8.3 million years between the two methods. These results indicate that, in some
      cases, taxonomically diagnostic characters may be maintained among divergent
      lineages for millions of years. In other cases, similar phenotypic characters
      among non-sister taxa, including reproductive strategies, suggest the potential
      for convergent evolution due to similar selective pressures among distinct
      lineages. Our analyses provide evidence of population expansions predating the
      last glacial maximum in the sampled lineages. These results suggest that
      Pleistocene glaciations were not inherently unfavorable or restrictive for some
      Melanohalea species, albeit with apparently different demographic histories
      between sexually and vegetatively reproducing lineages. CONCLUSIONS: Our results
      contribute to the understanding of how major changes during the Miocene and
      Pliocene have been important in promoting diversification within common lichen
      forming fungi in the northern Hemisphere. Additionally, we provide evidence that
      glacial oscillations have influenced current population structure of broadly
      distributed lichenized fungal species throughout the Holarctic.

PMID- 22963134
TI  - Polynomial-time algorithms for building a consensus MUL-tree.
AB  - A multi-labeled phylogenetic tree, or MUL-tree, is a generalization of a
      phylogenetic tree that allows each leaf label to be used many times. MUL-trees
      have applications in biogeography, the study of host-parasite cospeciation, gene
      evolution studies, and computer science. Here, we consider the problem of
      inferring a consensus MUL-tree that summarizes a given set of conflicting MUL
      trees, and present the first polynomial-time algorithms for solving it. In
      particular, we give a straightforward, fast algorithm for building a strict
      consensus MUL-tree for any input set of MUL-trees with identical leaf label
      multisets, as well as a polynomial-time algorithm for building a majority rule
      consensus MUL-tree for the special case where every leaf label occurs at most
      twice. We also show that, although it is NP-hard to find a majority rule
      consensus MUL-tree in general, the variant that we call the singular majority
      rule consensus MUL-tree can be constructed efficiently whenever it exists.

PMID- 22963135
TI  - Carbamoyl pyridone HIV-1 integrase inhibitors. 1. Molecular design and
      establishment of an advanced two-metal binding pharmacophore.
AB  - Our group has focused on expanding the scope of a two-metal binding pharmacophore
      concept to explore HIV-1 integrase inhibitors through medicinal chemistry efforts
      to design novel scaffolds which allow for improvement of pharmacokinetic (PK) and
      resistance profiles. A novel chelating scaffold was rationally designed to
      effectively coordinate two magnesium cofactors and to extend an aromatic group
      into an optimal hydrophobic pharmacophore space. The new chemotype, consisting of
      a carbamoyl pyridone core unit, shows high inhibitory potency in both enzymatic
      and antiviral assay formats with low nM IC50 and encouraging potency shift
      effects in the presence of relevant serum proteins. The new inhibitor design
      displayed a remarkable PK profile suggestive of once daily dosing without the
      need for a PK booster as demonstrated by robust drug concentrations at 24 h after
      oral dosing in rats, dogs, and cynomolgus monkeys.

PMID- 22963136
TI  - Possible predictive value of maspin expression in colorectal cancer.
AB  - INTRODUCTION: The aim of our study was to correlate Maspin expression, a serine
      protease with possible antiangiogenic and antiproliferative effects, with
      angiogenesis and to realize a synthesis of the literature data regarding the
      novel patented compounds used in colorectal cancer (CRC). MATERIALS AND METHODS:
      In 110 cases with CRC, immunohistochemical stains were performed using Maspin,
      p53, VEGFA, CD31, and CD105. The results were correlated with the tumor stage and
      microsatellite status. A new scoring system for Maspin, based on the dual
      cytoplasmic-nuclear expression, with possible predictive value, was proposed.
      RESULTS: The angiogenesis presented an oscillating pattern, the VEGF expression
      was more intense in Stage IV, but the endothelial area that quantified with both
      CD31 and CD105 was smaller than in those cases diagnosed in Stages II and III.
      Most of the p53 negative cases with Maspin nuclear predominance, which seems to
      respond to 5-Fluorouracil, were microsatellite instability (MSI) cases. In Stage
      II, Maspin nuclear positivity was more specific for pT4 tumors and aggressive
      cases with high p53 index. Thirty-three percent of CRC diagnosed in Stage II and
      27% of those from Stage III presented Maspin expression in the endothelial cells.
      No cases from Stage IV had Maspin vascular positivity. CONCLUSIONS: Maspin
      nuclear expression, associated with p53 ones, might be used either to select the
      high-risk microsatellite stable (MSS) colorectal carcinomas diagnosed in Stage II
      or those MSI cases which can respond to 5-Fluorouracil.

PMID- 22963137
TI  - Genetic variation in SPAG16 regions encoding the WD40 repeats is not associated
      with reduced sperm motility and axonemal defects in a population of infertile
      males.
AB  - BACKGROUND: SPAG16 is a critical structural component of motile cilia and
      flagella. In the eukaryotic unicellular algae Chlamydomonas, loss of gene
      function causes flagellar paralysis and prevents assembly of the "9 + 2" axoneme
      central pair. In mice, we have previously shown that loss of Spag16 gene function
      causes male infertility and severe sperm motility defects. We have also reported
      that a heterozygous mutation of the human SPAG16 gene reduces stability of the
      sperm axonemal central apparatus. METHODS: In the present study, we analyzed DNA
      samples from 60 infertile male volunteers of Western European (Italian) origin,
      to search for novel SPAG16 gene mutations, and to determine whether increased
      prevalence of SPAG16 single nucleotide polymorphisms (SNPs) was associated with
      infertility phenotypes. Semen parameters were evaluated by light microscopy and
      sperm morphology was comprehensively analyzed by transmission electron microscopy
      (TEM). RESULTS: For gene analysis, sequences were generated covering exons
      encoding the conserved WD40 repeat region of the SPAG16 protein and the flanking
      splice junctions. No novel mutations were found, and the four SNPs in the
      assessed gene region were present at expected frequencies. The minor alleles were
      not associated with any assessed sperm parameter in the sample population.
      CONCLUSIONS: Analysis of the SPAG16 regions encoding the conserved WD repeats
      revealed no evidence for association of mutations or genetic variation with sperm
      motility and ultrastructural sperm characteristics in a cohort of Italian
      infertile males.

PMID- 22963138
TI  - Case of coexisting psoriatic arthritis and bullous pemphigoid improved by
      etanercept.

PMID- 22963139
TI  - Binding analysis of ytterbium(III) complex containing 1,10-phenanthroline with
      DNA and its antimicrobial activity.
AB  - To evaluate the biological preference of [Yb(phen)2(OH2)Cl3](H2O)2 (phen is 1,10
      phenanthroline) for DNA, interaction of Yb(III) complex with DNA in Tris-HCl
      buffer is studied by various biophysical and spectroscopic techniques which
      reveal that the complex binds to DNA. The results of fluorescence titration
      reveal that [Yb(phen)2(OH2)Cl3](H2O)2 has strongly quenched in the presence of
      DNA. The binding site number n, apparent binding constant K b, and the Stern
      Volmer quenching constant K SV are determined. DeltaH0, DeltaS0, and DeltaG0 are
      obtained based on the quenching constants and thermodynamic theory (DeltaH0 > 0,
      DeltaS0 > 0, and DeltaG0 < 0). The experimental results show that the Yb(III)
      complex binds to DNA by non-intercalative mode. Groove binding is the preferred
      mode of interaction for [Yb(phen)2(OH2)Cl3](H2O)2 to DNA. The DNA cleavage
      results show that in the absence of any reducing agent, Yb(III) complex can
      cleave DNA. The antimicrobial screening tests are also recorded and give good
      results in the presence of Yb(III) complex.

PMID- 22963140
TI  - Rehabilitation of spelling in a participant with a graphemic buffer impairment:
      the role of orthographic neighbourhood in remediating the serial position effect.
AB  - Graphemic Output Buffer (GOB) disorder is defined as difficulty with the serial
      output of a sequence of letters in the output stage of the spelling process. In
      their rehabilitation study with a GOB patient, Sage and Ellis ( 2006 ) found that
      improvement on treated words generalised to untreated words from the same
      orthographic neighbourhoods as treated items, but not to other unrelated words.
      GOB patients frequently show a bow-shaped accuracy curve across letter positions,
      where letters at the middle positions are most error-prone. It may be that
      consistent letters at these middle letter positions across neighbourhoods
      modulate this effect. Spelling was treated using an Anagram and Copy Treatment
      (ACT) and generalisation to three untreated sets was examined: (1) neighbours of
      treated words with shared middle letters (e.g., clock-block), (2) neighbours with
      different medial position letters (e.g., clock-click), and (3) unrelated words
      (e.g., clock-puppy). Improvement was found for untreated neighbours with shared
      middle letters. There was no effect of training on the unrelated word set, and a
      negative impact on untreated neighbours with changed middle letters after the
      treatment. We attribute these results to top-down support from learned lexical
      representations, which facilitate spelling of untreated neighbours with shared
      middle letters but impede neighbours with changed middle letters. This latter
      result is attributed to interference from neighbours in the trained set
      strengthening competing letter representations at middle positions.

PMID- 22963143
TI  - Role of noncoplanar conformation in facilitating ground state hole transfer in
      oxidized porphyrin dyads.
AB  - We employ density functional theory to investigate ground state hole transfer in
      covalently linked oxidized zinc-zinc porphyrin ([ZnZn](+)) and zinc-free-base
      porphyrin ([ZnFb](+)) dyads in both coplanar and noncoplanar (tilted)
      conformations. We obtain reactant, product, and transition state (TS) for the
      hole transfer reaction in the [ZnZn](+) system. The hole is localized on a single
      porphyrin unit in the reactant and product states while delocalized in the TS,
      implying the dominance of superexchange mechanism in the hole transfer reaction.
      A metastable as well as stable states are located for the [ZnFb](+) system while
      no TS is found, indicating a barrierless hole transfer reaction. The hole
      lifetimes are calculated to be 15.80 and 0.034 ns for [ZnZn](+) in the coplanar
      and tilted conformation, respectively, and 14.45 and 0.313 ns for [ZnFb](+). The
      hole transfer rates are found to be several orders of magnitude faster in the
      tilted conformation than in the coplanar conformation for both dyads, showing the
      importance of noncoplanar conformation between the two porphyrin pigments in
      facilitating the hole transfer process. We also show that inclusion of solvent
      effects in calculations plays an important role in the proper ground state hole
      localization in oxidized dyads. These results provide an unconventional insight
      into the hole transfer mechanism in porphyrin arrays and are relevant to design
      of artificial photoharvesting materials.

PMID- 22963144
TI  - Desensitization to antibiotics in children.
AB  - Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are
      among the most common cause for this kind of reactions. Drug hypersensitivity may
      affect any organ or system, and manifestations range widely in clinical severity
      from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided
      in the future. In case of infection, there is usually a safe antibiotic
      alternative. Nonetheless, in some cases, no alternative treatment exists for
      optimal therapy. Under these circumstances, desensitization may be performed.
      Drug desensitization is defined as the induction of a temporary state of
      tolerance to a drug which can only be maintained by continuous administration of
      the medication responsible for the hypersensitivity reaction. Desensitization is
      mainly performed in IgE-mediated reactions. Increasing doses of the implicated
      drug are administered over a short period of time, until the therapeutic dose is
      achieved and tolerated. Very few studies confined to children are found in
      literature. Most of them are case reports. In general, the proposed
      desensitization schemes are similar to those used in adults differing only in the
      final dose administered. The purpose of this study is to review desensitization
      to antibiotics in children presenting and discussing three clinical practical
      cases of desensitization in this age group.

PMID- 22963145
TI  - Disentangling the temporal relationship between parental depressive symptoms and
      early child behavior problems: a transactional framework.
AB  - Despite the considerable amount of research demonstrating the relationship
      between parental depressive symptoms and child behavior problems, few studies
      have examined the direction of the relationship between these variables.
      Therefore, the purpose of this study was to examine transactional effects between
      parental depressive symptoms and child behavior problems. Participants were 209
      parent-child dyads drawn from the Oregon Adolescent Depression Project who
      completed at least 2 of 4 annual questionnaire assessments between the child's
      age of 4 and 7 years. Structural equation modeling was used to examine the
      autoregressive paths from one year to the next year within each construct, as
      well as cross-lagged paths from one year to the next year between constructs.
      Findings indicated that parental depressive symptoms at each year predicted child
      behavior problems at the subsequent year and vice versa. No support was found for
      differential gender effects. These findings highlight the reciprocal relationship
      between parental depressive symptoms and child behavior problems and suggest
      intervention programs for young children should assess for and target parental
      depression when appropriate. Future research should examine these relationships
      across a broader developmental spectrum and in more diverse, heterogeneous
      samples.

PMID- 22963146
TI  - Association between the ABO locus and hematological traits in Korean.
AB  - BACKGROUND: Recently, genome-wide association studies identified a pleiotropic
      gene locus, ABO, as being significantly associated with hematological traits. To
      confirm the effects of ABO on hematological traits, we examined the link between
      the ABO locus and hematological traits in Korean population-based cohorts.
      RESULTS: Six tagging SNPs for ABO were analyzed with regard to their effects on
      hematological traits [white blood cell count (WBC), red blood cell count (RBC),
      platelet (Plat), mean corpuscular volume (MCV), and mean corpuscular haemoglobin
      concentration (MCHC)]. Linear regression analyses were performed, controlling for
      recruitment center, sex, and age as covariates. Of the 6 tagging SNPs, 3
      (rs2073823, rs8176720, and rs495828) and 3 (rs2073823, rs8176717, and rs687289)
      were significantly associated with RBC and MCV, respectively (Bonferroni
      correction p-value criteria < 0.05/6 = 0.008). rs2073823 and a reported SNP
      (rs8176746), as well as rs495828 and a reported SNP (rs651007), showed perfect
      linkage disequilibrium status (r2s = 0.99). Of the remaining 3 SNPs (rs8176720,
      rs8176717 and rs687289), rs8176717 generated an independent signal with moderate
      p-value (= 0.045) when it was adjusted for by rs2073823 (the most significant
      SNP). We also identified a copy number variation (CNV) that was tagged by the SNP
      rs8176717, the minor allele of which correlated with the deletion allele of CNV.
      Our haplotype analysis indicated that the haplotype that contained the CNV
      deletion was significantly associated with MCV (beta +/- se = 0.363 +/- 0.118, p
      =2.09 * 10-3). CONCLUSIONS: Our findings confirm that ABO is one of the genetic
      factors that are associated with hematological traits in the Korean population.
      This result is notable, because GWASs fail to evaluate the link between a CNV and
      phenotype traits.

PMID- 22963147
TI  - Real time monitoring of biofilm development under flow conditions in porous
      media.
AB  - Biofilm growth can impact the effectiveness of industrial processes that involve
      porous media. To better understand and characterize how biofilms develop and
      affect hydraulic properties in porous media, both spatial and temporal
      development of biofilms under flow conditions was investigated in a translucent
      porous medium by using Pseudomonas fluorescens HK44, a bacterial strain
      genetically engineered to luminesce in the presence of an induction agent. Real
      time visualization of luminescent biofilm growth patterns under constant pressure
      conditions was captured using a CCD camera. Images obtained over 8 days revealed
      that variations in bioluminescence intensity could be correlated to biofilm cell
      density and hydraulic conductivity. These results were used to develop a real
      time imaging method to study the dynamic behavior of biofilm evolution in a
      porous medium, thereby providing a new tool to investigate the impact of
      biological fouling in porous media under flow conditions.

PMID- 22963148
TI  - A dinitrosyliron complex within the homoleptic Fe(NO)4 anion: NO as nitroxyl and
      nitrosyl ligands within a single structure.
AB  - Nitrosylation of the chelate-thiolate-containing dinitrosyliron complex (DNIC)
      [(S(CH(2))(3)S)Fe(NO)(2)](-) triggers nitric oxide (NO) activation to generate
      the homoleptic nitrosyl {Fe(NO)(2)}(9) DNIC [Fe(NO)(4)](-) (1) made up of two
      nitroxyls (or two NO anions) attached to a delocalized {Fe(NO)(2)}(9) motif. The
      significantly longer N3-O3/N4-O4 [1.380(12) and 1.280(12) A] and Fe1-N3/Fe1-N4
      [2.008(11) and 2.045(10) A] bond distances reflect that N3-O3 and N4-O4 of
      complex 1 may act as the nitroxyl-coordinated ligands. That is, the electronic
      structure of the DNIC 1 is best described as a {Fe(NO)(2)}(9) motif coordinated
      by two nitroxyl (NO(-)) ligands.

PMID- 22963149
TI  - The Eczema Priority Setting Partnership: a collaboration between patients,
      carers, clinicians and researchers to identify and prioritize important research
      questions for the treatment of eczema.
AB  - BACKGROUND: Eczema is a common condition, yet there are uncertainties regarding
      many frequently used treatments. Knowing which of these uncertainties matter to
      patients and clinicians is important, because they are likely to have different
      priorities from those of researchers and funders. OBJECTIVES: To identify the
      uncertainties in eczema treatment that are important to patients who have eczema,
      their carers and the healthcare professionals (HCPs) who treat them. METHODS: An
      eczema Priority Setting Partnership was established, including patients, HCPs and
      researchers. Eczema treatment uncertainties were gathered from patients and
      clinicians, and then prioritized in a transparent process, using a methodology
      advocated by the James Lind Alliance. RESULTS: In the consultation stage 493
      participants (including 341 patients/carers) made 1070 submissions, of which 718
      were uncertainties relating to the treatment of eczema. Treatment uncertainties
      with more than one submission were grouped into 52 'indicative uncertainties',
      which were then ranked by 514 participants (including 399 patients/carers). The
      top 14 treatment uncertainties were prioritized for research. The first four were
      common to patients/carers and HCPs (shared uncertainties): (i) the best and
      safest way of using topical steroids (including frequency of application,
      potency, length of time, alternation with other topical treatments and age
      limits); (ii) the long-term safety of topical steroids; (iii) the role of food
      allergy tests; and (iv) the most effective and safe emollients in treating
      eczema. The remaining 10 of the top 14 uncertainties comprised the next five
      highest ranked uncertainties for patients and the next five highest ranked
      uncertainties for HCPs. At a workshop involving 40 participants (patients, HCPs
      and researchers), shared uncertainties were formulated into possible research
      questions. CONCLUSIONS: The top 14 treatment uncertainties around the treatment
      of eczema provide guidance for researchers and funding bodies to ensure that
      future research answers questions that are important to both clinicians and
      patients.

PMID- 22963150
TI  - Hospitalisation costs and duration of elderly motorcyclists' non-fatality crashes
      in Taiwan.
AB  - This paper investigates the relationship between medical treatment costs and the
      length of hospital stays resulting from motorcycle crashes involving the elderly.
      The World Health Organization defines 'elderly' as people more than 65 years old.
      The sample for this study consisted of data for the year 2007 collected by the
      Bureau of National Health Insurance, Taiwan. We develop models for predicting
      medical costs and the length of hospital stays based on diagnosis, hospital and
      user types. The seemingly unrelated regression equation (SURE) model was applied
      first to investigate the relationship between medical costs and the length of
      hospital stays. The SURE model shows that the type of injury (e.g. head injury)
      is statistically significant and has positive effects on medical costs for
      motorcycle crashes involving the elderly in Taiwan. Due to the statistical
      insignificance of the dependency between medical costs and length of hospital
      stays, two separate simple linear regression models were subsequently estimated.
      For motorcycle crashes, patients over 80 years old had the highest medical costs.
      The findings reinforce the need for transportation authorities to focus on
      preventing certain types of injuries that are particularly serious and costly for
      the elderly in Taiwan.

PMID- 22963151
TI  - Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3
      cell apoptosis.
AB  - Isoliquiritigenin (ISL), a licorice chalconoid, is a bioactive agent with
      chemopreventive potential that has been patented for tumor treatment in China.
      This study investigated the mechanisms of ISL-induced apoptosis in ovarian
      carcinoma SKOV-3 cells. Cell viability was evaluated using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The apoptotic rate
      was determined via flow cytometry using an annexin V-FITC apoptosis detection
      kit. The intracellular reactive oxygen species (ROS) levels were assessed using a
      2,7-dichlorofluorescein probe assay. Malondialdehyde (MDA) formation was
      determined via thiobarbituric acid reactive substance test. The expressions of
      growth arrest and DNA damage-inducible gene (GADD153/CHOP), 78 kDa glucose
      regulated protein (GRP 78), alpha-subunit of eukaryotic initiation factor 2
      (eIF2alpha) phosphorylation, activating transcription factor 6alpha (ATF6alpha),
      and unspliced form of X-box binding protein1 (XBP1U) were analyzed via Western
      blot. Caspase-3 and caspase-12 activities were assessed using a fluorometric kit.
      Findings indicate that ISL significantly inhibits SKOV-3 cell proliferation,
      increases intracellular ROS levels, and causes SKOV-3 cell apoptosis. Moreover,
      ISL-exposed SKOV-3 cells trigger endoplasmic reticulum (ER) stress, as indicated
      by the enhancement of ER stress-related molecules p-eIF2alpha, GADD153/CHOP,
      GRP78, XBP1 expression, and cleavage of ATF6alpha. However, caspase-12 inhibitor
      (Z-ATAD) effectively and partially prevents ROS and MDA formation and inhibits
      ISL-induced SKOV-3 cell apoptosis. ISL induces apoptosis via ER stress-triggered
      signaling pathways in SKOV-3 cells. ER stress-induced cancer cell apoptosis has
      been discussed in some patents.

PMID- 22963152
TI  - An educational training simulator for advanced perfusion techniques using a high
      fidelity virtual patient model.
AB  - The operation of cardiopulmonary bypass procedure requires an advanced skill in
      both physiological and mechanical knowledge. We developed a virtual patient
      simulator system using a numerical cardiovascular regulation model to manage
      perfusion crisis. This article evaluates the ability of the new simulator to
      prevent perfusion crisis. It combined short-term baroreflex regulation of venous
      capacity, vascular resistance, heart rate, time-varying elastance of the heart,
      and plasma-refilling with a simple lumped parameter model of the cardiovascular
      system. The combination of parameters related to baroreflex regulation was
      calculated using clinical hemodynamic data. We examined the effect of differences
      in autonomous-nerve control parameter settings on changes in blood volume and
      hemodynamic parameters and determined the influence of the model on operation of
      the control arterial line flow and blood volume during the initiation and weaning
      from cardiopulmonary bypass. Typical blood pressure (BP) changes (hypertension,
      stable, and hypotension) were reproducible using a combination of four control
      parameters that can be estimated from changes in patient physiology, BP, and
      blood volume. This simulation model is a useful educational tool to learn the
      recognition and management skills of extracorporeal circulation. Identification
      method for control parameter can be applied for diagnosis of heart failure.

PMID- 22963153
TI  - Inhibitory effect of interferon-gamma on experimental tooth movement in mice.
AB  - The aim of this study was to investigate the effects of interferon (IFN)-gamma on
      experimental tooth movement in mice using a murine experimental tooth movement
      model. An Ni-Ti closed-coil spring was inserted between the upper-anterior
      alveolar bones and the upper-left first molars in mice. We evaluated the
      relationship between local Ifn-gamma mRNA levels and orthodontic tooth movement.
      In other experiments, IFN-gamma was injected adjacent to each first molar every
      other day during tooth movement. After 12 days, the amount of tooth movement was
      measured. Tartrate-resistant acid phosphatase (TRAP)-positive cells at the
      pressure side of each experimental tooth were counted as osteoclasts. Local Ifn
      gamma mRNA expression increased with orthodontic tooth movement. The number of
      TRAP-positive cells increased on the pressure side of the first molar. In
      contrast, the degree of tooth movement and the number of TRAP-positive cells on
      the pressure side in IFN-gamma-injected mice were less than those of control
      mice. IFN-gamma was induced in experimental tooth movement, and could inhibit
      mechanical force-loaded osteoclastogenesis and tooth movement. These results
      suggest that IFN-gamma might be useful in controlling orthodontic tooth movement
      because of its inhibitory action on excessive osteoclastogenesis during this
      movement.

PMID- 22963154
TI  - Perimenopause and incidence of depression in midlife women: a population-based
      study in Taiwan.
AB  - AIM: To examine the relationships between depressive symptoms, menopausal status,
      and menopausal symptoms in middle-aged women. MATERIAL AND METHODS: This cross
      sectional, population-based study involved patients in the Taiwanese community.
      Data were retrieved from the nationwide 2002 Health Promotion Knowledge,
      Attitude, and Performance Survey in Taiwan. We assessed depressive symptoms using
      the Taiwanese Depression Questionnaire with a cut-off point of 18 of 19. Self
      reported perception of menopausal status, frequency of menstrual periods in the
      preceding 12 months, and a history of oophorectomy surgery were used to
      categorize the women's menopausal status into premenopause, perimenopause,
      postmenopause, and surgical menopause. RESULTS: A total of 3359 women aged 40-55
      years were selected. Among these patients, 145 women (4.7%) experienced higher
      levels of concurrent depressive symptoms. The increase in depressive symptoms was
      significantly associated with menopausal status and most of the menopausal
      symptoms. After controlling for age, marital status, education, income, smoking,
      hormone therapy, and menopause symptoms, multivariate logistic regression showed
      that perimenopause was still significantly associated with depression in midlife
      women (odds ratio 1.97; 95% confidence interval 1.24-3.14). CONCLUSION:
      Independent of menopausal symptoms, perimenopausal status increases the risk of
      depression.

PMID- 22963156
TI  - Insured without moral hazard in the health care reform of China.
AB  - Public insurance possibly increases the use of health care because of the insured
      person's interest in maximizing benefits without incurring out-of-pocket costs. A
      newly reformed public insurance scheme in China that builds on personal
      responsibility is thus likely to provide insurance without causing moral hazard.
      This possibility is the focus of this study, which surveyed 303 employees in a
      large city in China. The results show that the coverage and use of the public
      insurance scheme did not show a significant positive effect on the average
      employee's frequency of physician consultation. In contrast, the employee who
      endorsed public responsibility for health care visited physicians more frequently
      in response to some insurance factors. On balance, public insurance did not tempt
      the average employee to consult physicians frequently, presumably due to personal
      responsibility requirements in the insurance scheme.

PMID- 22963155
TI  - Sexual function and chemotherapy in postmenopausal women with breast cancer.
AB  - BACKGROUND: This cross-sectional, nested cohort study assessed Female Sexual
      Function Index (FSFI) scores in postmenopausal women with breast cancer receiving
      primary chemotherapy. METHODS: The FSFI questionnaire was administered to 24
      postmenopausal women one month after diagnosis of breast cancer (post-diagnosis
      group) and one month after completion of the first cycle of primary anthracyclin
      based chemotherapy (post-chemotherapy group). Scores were compared to those of 24
      healthy postmenopausal women seeking routine gynecological care (control group).
      All patients were sexually active at the time of enrollment. Mean age was 57.29
      +/- 11.82 years in the breast cancer group and 52.58 +/- 7.19 years in the
      control group. RESULTS: Scores in all domains of the FSFI instrument were
      significantly lower in the post-diagnosis group than in controls (-41.3%, p <
      0.001). A further major reduction in FSFI scores was evident on completion of one
      cycle of primary chemotherapy (down 46.7% from post-diagnosis scores, p < 0.003),
      again in all domains. Six patients (25%) ceased all sexual relations, in a
      significant change from baseline (p < 0.001). After one chemotherapy cycle, a
      further five patients ceased sexual activity, for a total of 11 (45.8%)
      participants--a borderline significant difference (p = 0.063). CONCLUSION: The
      present study shows that female sexual function as assessed by the FSFI declines
      significantly at two distinct points in time: upon diagnosis of breast cancer and
      after administration of systemic chemotherapy.

PMID- 22963157
TI  - An explanatory model for state Medicaid per capita prescription drug
      expenditures.
AB  - Rising prescription drug expenditure is a growing concern for publicly funded
      drug benefit programs like Medicaid. To be able to contain drug expenditures in
      Medicaid, it is important that cause(s) for such increases are identified. This
      study attempts to establish an explanatory model for Medicaid prescription drugs
      expenditure based on the impacts of key influencers/predictors identified using a
      comprehensive framework of drug utilization. A modified Andersen's behavior model
      of health services utilization is employed to identify potential determinants of
      pharmaceutical expenditures in state Medicaid programs. Level of federal matching
      funds, access to primary care, severity of diseases, unemployment, and education
      levels were found to be key influencers of Medicaid prescription drug
      expenditure. Increases in all, except education levels, were found to result in
      increases in drug expenditures. Findings from this study could better inform
      intervention policies and cost-containment strategies for state Medicaid drug
      benefit programs.

PMID- 22963158
TI  - Beyond access: extending our thinking on health policy.
AB  - Expanding access is often seen as a panacea for health problems. Although access
      is a necessary step, it is also important that policy analysts do not fail to
      consider postaccess issues. Increased access to health is often assumed to be
      synonymous with improved health outcomes; however, just because access exists
      does not mean (1) that everyone will take advantage of access to resources or (2)
      that those taking advantage of access will necessarily see improved outcomes.
      This article focuses on three aspects of health policy, (1) the types of
      postaccess issues that exist, (2) the "if you build it, they will come" syndrome,
      and (3) updating the Anderson/Aday model of health care access to better
      theoretically understand postaccess issues.

PMID- 22963159
TI  - African American infant mortality and the Genesee County, MI REACH 2010
      initiative: an evaluation of the Undoing Racism Workshop.
AB  - The authors examine African American African American and White socioeconomic and
      infant mortality outcomes in Genesee County, Michigan, assess the stated effects
      of the Undoing Racism Workshop (URW) on its participants and the greater-Genesee
      County community, and introduce the ecological approach to the cycle of
      socialization as a tool to help identify sources of racially linked tension and
      sites for ameliorative intervention. Findings show that African Americans in
      Flint are geographically and socioeconomically isolated, have fewer resources to
      sustain health, and experience higher rates of infant mortality when compared to
      Whites in Flint's surrounding suburbs. Between two thirds and three fourths of
      URW follow-up survey respondents endorse the belief that the URW can help reduce
      infant mortality, and results suggest the workshop helps elicit individual and
      institutional/policy-related changes intended to lessen the disparity. Authors
      assert the URW offers a common language and framework for discussing racism as a
      structural phenomenon rather than merely racial prejudice within individuals.

PMID- 22963160
TI  - Alcohol use and policy formation: an evolving social problem.
AB  - This article explores the evolutionary course that the social problem of alcohol
      use has taken in the United States since the Colonial Era. This article utilizes
      a range of theoretical models to analyze the evolving nature of alcohol use from
      an unrecognized to a perceived social problem. The models used include critical
      constructionism (Heiner, 2002), top-down policy model (Dye, 2001) and
      Mauss'(1975) understanding of social problems and movements. These theoretical
      constructs exhibit the relative nature of alcohol use as a social problem in
      regards to a specific time, place, and social context as well as the powerful and
      influential role that social elites have in defining alcohol asa social problem.
      Studies regarding the development of alcohol policy formation are discussed to
      illuminate the different powers, constituents, and factors that play a role in
      alcohol policy formation.Finally, implications for future study are discussed
      [corrected].

PMID- 22963161
TI  - Reunifying from behind bars: a quantitative study of the relationship between
      parental incarceration, service use, and foster care reunification.
AB  - Incarcerated parents attempting to reunify with their children in foster care can
      find it difficult to complete the activities on their court-ordered case plans,
      such as drug treatment services and visitation with children. Although much has
      been written regarding the obstacles that are likely to interfere with
      reunification for incarcerated parents, very little quantitative research has
      examined the topic. This study uses secondary data to examine the incarceration
      experiences and reunification outcomes of a sample of 225 parents in one large
      urban California county. In multivariate analysis controlling for problems and
      demographics, incarcerated parents were less likely to reunify with their
      children; however, service use appeared to mediate this relationship, as the
      negative association between incarceration and reunification did not persist when
      service use was included as a variable in the model. Suggestions are made for
      policy and practice changes to improve reunification outcomes for this population
      of parents.

PMID- 22963163
TI  - Insensitivity to scope in contingent valuation studies: reason for dismissal of
      valuations?
AB  - BACKGROUND: The credibility of contingent valuation studies has been questioned
      because of the potential occurrence of scope insensitivity, i.e. that respondents
      do not react to higher quantities or qualities of a good. OBJECTIVE: The aim of
      this study was to examine the extent of scope insensitivity and to assess the
      relevance of potential explanations that may help to shed light on how to
      appropriately handle this problem in contingent valuation studies. METHODS: We
      surveyed a sample of 2004 men invited for cardiovascular disease screening. Each
      respondent had three contingent valuation tasks from which their sensitivity to
      larger risk reductions (test 1) and to change in travel costs associated with
      participation (test 2) could be assessed. Participants were surveyed while
      waiting for their screening session. Non-participants were surveyed by postal
      questionnaire. RESULTS: The sample was overall found to be sensitive to scope,
      testing at the conventional sample-mean level. At the individual respondent
      level, however, more than half of the respondents failed the tests. Potential
      determinants for failing the tests were examined in alternative regression models
      but few consistent relationships were identified. One exception was the influence
      of more detailed information, which was positively associated with willingness to
      pay and negatively associated with scope sensitivity. CONCLUSION: Possible
      explanations for scope insensitivity are discussed; if cognitive limitations,
      emotional load and mental budgeting explain scope insensitivity there are grounds
      for rejecting valuations, whereas other factors such as the alternative
      theoretical framework of regret theory may render insensitivity to scope a result
      of rational thinking. It is concluded that future contingent valuation studies
      should focus more on extracting the underlying motives for the stated preferences
      in order to appropriately deal with responses that are seemingly irrational, and
      which may lead to imprecise welfare estimates.

PMID- 22963164
TI  - Course, outcomes, and psychosocial interventions for first-episode mania.
AB  - OBJECTIVES: The course of bipolar disorder tends to worsen over time,
      highlighting the importance of early intervention. Despite the recognized need
      for adjunctive psychosocial treatments in first-episode mania, very few studies
      have evaluated psychological interventions for this period of significant risk.
      In this empirical review, we evaluate existing research on first-episode bipolar
      disorder, compare this body of research to parallel studies of first-episode
      schizophrenia, and identify strategies for future research. METHODS: A
      comprehensive literature search of the MEDLINE and PsychINFO databases was
      conducted to identify studies of first-episode mania, as well as first-episode
      schizophrenia. Recovery and relapse rates were compared across studies. RESULTS:
      In contrast to a number of studies of first-episode schizophrenia, the authors
      identified only seven independent programs assessing first-episode mania.
      Findings from these studies suggest that, while pharmacological treatment helps
      patients achieve recovery from acute episodes, it fails to bring patients to
      sustained remission. Early psychosocial intervention may be imperative in
      reducing residual symptoms, preventing recurrence of mood episodes, and improving
      psychosocial functioning. However, very few studies of psychosocial interventions
      for first-episode mania have been systematically studied. CONCLUSIONS: Studies of
      first-episode mania indicate a gap between syndromal/symptomatic and functional
      recovery. Novel psychosocial interventions for first-episode mania may help
      bridge this gap, but require controlled study.

PMID- 22963165
TI  - Two Japanese cases of dermatitis herpetiformis associated each with lung cancer
      and autoimmune pancreatitis but showing no intestinal symptom or circulating
      immunoglobulin A antibodies to any known antigens.
AB  - Dermatitis herpetiformis (DH) is common in some Caucasian populations but
      extremely rare in Japanese, probably because of different immunogenetic
      backgrounds. We report two Japanese DH cases with typical clinical, histological
      and direct immunofluorescence features. However, no symptom of gluten-sensitive
      enteropathy was shown. The diagnosis was confirmed by eliminating other
      autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked
      immunosorbent assays and immunoblotting. However, circulating immunoglobulin
      (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA
      antibodies to tissue and epidermal transglutaminases were also negative. One case
      was associated with lung cancer and the other one with autoimmune pancreatitis.
      On review of 17 cases of DH reported in Japan over the previous 10 years,
      including our cases, one case was associated with gluten-sensitive enteropathy,
      four with malignant neoplasms, two with autoimmune systemic disorders and one
      with psoriasis. Although our cases were typical of DH in clinical,
      histopathological and IgA deposit features, they showed different human leukocyte
      antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA
      antibodies, including those to epidermal and tissue transglutaminases. These
      results suggest that studies of unique characteristics in Japanese DH patients
      should facilitate further understanding of pathogenesis in DH.

PMID- 22963166
TI  - Development of selective, potent RabGGTase inhibitors.
AB  - Members of the Ras superfamily of small GTPases are frequently mutated in cancer.
      Therefore, inhibitors have been developed to address the acitivity of these
      GTPases by inhibiting their prenylating enzymes FTase, GGTase I, and RabGGTase.
      In contrast to FTase and GGTase I, only a handful of RabGGTase inhibitors have
      been developed. The most active RabGGTase inhibitor known until recently was an
      FTase inhibitor which hit RabGGTase as an off-target. We recently reported our
      efforts to tune the selectivity of these inhibitors toward RabGGTase. Here we
      describe an extended set of selective inhibitors. The requirements for selective
      RabGGTase inhibitors are described in detail, guided by multiple crystal
      structures. In order to relate in vitro and cellular activity, a high-throughput
      assay system to detect the attachment of [(3)H]geranylgeranyl groups to Rab was
      used. Selective RabGGTase inhibition allows the establishment of novel drug
      discovery programs aimed at the development of anticancer therapeutics.

PMID- 22963167
TI  - IsUnstruct: prediction of the residue status to be ordered or disordered in the
      protein chain by a method based on the Ising model.

PMID- 22963168
TI  - W-band time-resolved electron paramagnetic resonance study of light-induced spin
      dynamics in copper-nitroxide-based switchable molecular magnets.
AB  - Molecular magnets Cu(hfac)(2)L(R) represent a new type of photoswitchable
      materials based on exchange-coupled clusters of copper(II) with stable nitroxide
      radicals. It was found recently that the photoinduced spin state of these
      compounds is metastable on the time scale of hours at cryogenic temperatures,
      similar to the light-induced excited spin state trapping phenomenon well-known
      for many spin-crossover compounds. Our previous studies have shown that electron
      paramagnetic resonance (EPR) in continuous wave (CW) mode allows for studying the
      light-induced spin state conversion and relaxation in the Cu(hfac)(2)L(R) family.
      However, light-induced spin dynamics in these compounds has not been studied on
      the sub-second time scale so far. In this work we report the first time-resolved
      (TR) EPR study of light-induced spin state switching and relaxation in
      Cu(hfac)(2)L(R) with nanosecond temporal resolution. To enhance spectral
      resolution we used high-frequency TR EPR at W-band (94 GHz). We first discuss the
      peculiarities of applying TR EPR to the solid-phase compounds Cu(hfac)(2)L(R) at
      low (liquid helium) temperatures and approaches developed for
      photoswitching/relaxation studies. Then we analyze the kinetics of the excited
      spin state at T = 5-21 K. It has been found that the photoinduced spin state is
      formed at time delays shorter than 100 ns. It has also been found that the
      observed relaxation of the excited state is exponential on the nanosecond time
      scale, with the decay rate depending linearly on temperature. We propose and
      discuss possible mechanisms of these processes and correlate them with previously
      obtained CW EPR data.

PMID- 22963169
TI  - Pollen morphology of the platycodonoid group (Campanulaceae s. str.) and its
      systematic implications.
AB  - In this study, we examined the pollen morphology of the platycodonoid group in
      Campanulaceae s. str. using a scanning electronic microscope. We used pollen
      grains of 25 accessions representing 24 species of the Codonopsis complex
      (including Campanumoea, Cyclocodon, Leptocodon, and all three subgenera of
      Codonopsis), which is extremely controversial among authors for taxonomic
      treatment. Pollen morphology of all the other genera in the group observed by
      previous authors is taken into account in our discussion. A total of nine pollen
      types with two subtypes in the group were recognized and named for the first
      time. Molecular and morphological data imply that each pollen type corresponds to
      a natural group at generic level, and thus the mergence of Leptocodon with
      Codonopsis and the restoration of Cyclocodon as a separate genus are justifiable,
      and Codonopsis subg. Pseudocodonopsis, subg. Obconicicapsula, and two species of
      Codonopsis subg. Codonopsis (C. purpurea and C. chimiliensis) may be better
      classified as three independent genera separate from the core Codonopsis.

PMID- 22963170
TI  - Association of intradialytic hypotension and convective volume in
      hemodiafiltration: results from a retrospective cohort study.
AB  - BACKGROUND: Hemodiafiltration (HDF), as a convective blood purification
      technique, has been associated with favorable outcomes improved phosphate
      control, removal of middle-molecules such as Beta2-microglobulin and the
      occurrence of intradialytic hypotension (IDH) as compared to diffusive
      techniques. The aim of this retrospective cohort study in dialysis patients
      receiving HDF in one urban dialysis facility in Mexico City was to investigate
      the occurrence of IDH during HDF treatments with varying convective volume
      prescriptions. METHODS: Subjects were stratified into equal groups of percentiles
      of convective volume prescription: Group 1 of 0 to 7.53 liters, group 2 of 7.54
      to 14.8 liters, group 3 of 14.9 to 16.96 liters, group 4 of 16.97 to 18.9 liters,
      group 5 of 21 to 19.9 liters and group 6 of 21.1 to 30 liters. Logistic
      Regression with and without adjustment for confounding factors was used to
      evaluate factors associated with the occurrence of IDH. RESULTS: 2276 treatments
      of 154 patients were analyzed. IDH occurred during 239 HDF treatments (10.5% of
      all treatments). Group 1 showed 31 treatments (8.2%) with IDH whereas group 6
      showed IDH in only 15 sessions (4% of all treatments). Odds Ratio of IDH for
      Group 6 was 0.47 (95% CI 0.25 to 0.88) as compared to Group 1 after adjustment.
      CONCLUSIONS: In summary the data of this retrospective cohort study shows an
      inverse correlation between the occurrence of IDH and convective volume
      prescription. Further research in prospective settings is needed to confirm these
      findings.

PMID- 22963172
TI  - Recurrence and prognostic factors in patients with aggressive fibromatosis. The
      role of radical surgery and its limitations.
AB  - BACKGROUND: Surgery is still the standard treatment for aggressive fibromatosis
      (AF); however, local control remains a significant problem and the impact of R0
      surgery on cumulative recurrence (CR) is objective of contradictory reports.
      METHODS: This is a single-institution study of 62 consecutive patients affected
      by extra-abdominal and intra-abdominal AF who received macroscopically radical
      surgery within a time period of 15 years. RESULTS: Definitive pathology
      examination confirmed an R0 situation in 49 patients and an R1 in 13 patients.
      Five-year CR for patients who underwent R0 vs R1 surgery was 7.1% vs 46.4% (P =
      0.04) and for limbs vs other localizations 33.3% vs 9.9% (P = 0.02) respectively.
      In 17 patients who had intraoperative frozen section (IFS) margin evaluation R0
      surgery was more common (17 of 17 vs 32 of 45, P = 0.01) and CR lower (five-year
      CR 0% vs 19.1%, respectively, P = 0.04). However, in multivariate analysis only
      limb localization showed a negative impact on CR (HR: 1.708, 95% CI 1.03 to 2.84,
      P = 0.04). CONCLUSIONS: IFS evaluation could help the surgeon to achieve R0
      surgery in AF. Non-surgical treatment, including watchful follow-up, could be
      indicated for patients with limb AF localization, because of their high risk of
      recurrence even after R0 surgery.

PMID- 22963171
TI  - Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression
      in the degenerating human annulus.
AB  - BACKGROUND: In spite of its high clinical relevance, the relationship between
      disc degeneration and low back pain is still not well understood. Recent studies
      have shown that genome-wide gene expression studies utilizing ontology searches
      provide an efficient and valuable methodology for identification of clinically
      relevant genes. Here we use this approach in analysis of pain-, nerve-, and
      neurotrophin-related gene expression patterns in specimens of human disc tissue.
      Control, non-herniated clinical, and herniated clinical specimens of human
      annulus tissue were studied following Institutional Review Board approval.
      RESULTS: Analyses were performed on more generated (Thompson grade IV and V)
      discs vs. less degenerated discs (grades I-III), on surgically operated discs vs.
      control discs, and on herniated vs. control discs. Analyses of more degenerated
      vs. less degenerated discs identified significant upregulation of well-recognized
      pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and
      catechol-0-methyltransferase). Nerve growth factor was significantly upregulated
      in surgical vs. control and in herniated vs. control discs. All three analyses
      also found significant changes in numerous proinflammatory cytokine- and
      chemokine-related genes. Nerve, neurotrophin and pain-ontology searches
      identified many matrix, signaling and functional genes which have known
      importance in the disc. Immunohistochemistry was utilized to confirm the presence
      of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin
      receptor B1 at the protein level in the human annulus. CONCLUSIONS: Findings
      point to the utility of microarray analyses in identification of pain-,
      neurotrophin and nerve-related genes in the disc, and point to the importance of
      future work exploring functional interactions between nerve and disc cells in
      vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified
      numerous changes in proinflammatory cytokines and chemokines which also have
      significant relevance to disc biology. Since the degenerating human disc is
      primarily an avascular tissue site into which disc cells have contributed high
      levels of proinflammatory cytokines, these substances are not cleared from the
      tissue and remain there over time. We hypothesize that as nerves grow into the
      human annulus, they encounter a proinflammatory cytokine-rich milieu which may
      sensitize nociceptors and exacerbate pain production.

PMID- 22963173
TI  - Effects of furosemide on ureteral diameter and attenuation using computed
      tomographic excretory urography in normal dogs.
AB  - One of the limitations of computed tomographic excretory urography (CTEU) for
      diagnosis of ureteral disease in dogs is that normal ureteral peristalsis can
      cause intermittent and inconsistent filling. The aims of this study were to
      determine if the addition of furosemide to a standard CTEU protocol would
      increase identification of the ureteral segments, increase ureteral attenuation
      and increase ureteral diameter in normal dogs. Standard and furosemide-enhanced
      CTEU scans were acquired in 14 healthy dogs 3 and 10 minutes postcontrast.
      Ureteral diameters, attenuation values, and percent ureteral filling scores were
      recorded without the knowledge of furosemide treatment. Comparisons were made
      between treatments for each postcontrast scan time. The addition of furosemide to
      the CTEU protocol improved visualization of the ureters by significantly
      increasing the number of ureteral segments that were able to be identified, as
      well as their diameter when imaging the patient 3 min following contrast
      injection (P = 0.012). No major side effects were observed at the dose of 4
      mg/kg. There was no advantage to imaging dogs 10 min following contrast
      administration as the ureteral segments were less attenuating and a smaller
      percentage of the ureter could be identified. We conclude that the addition of
      furosemide to canine CTEU studies is safe and may help improve visualization of
      the ureters.

PMID- 22963174
TI  - How are number words mapped to approximate magnitudes?
AB  - How do we map number words to the magnitudes they represent? While much is known
      about the developmental trajectory of number word learning, the acquisition of
      the counting routine, and the academic correlates of estimation ability, previous
      studies have yet to describe the mechanisms that link number words to nonverbal
      representations of number. We investigated two mechanisms: associative mapping
      and structure mapping. Four dot array estimation tasks found that adults' ability
      to match a number word to one of two discriminably different sets declined as a
      function of set size and that participants' estimates of relatively large, but
      not small, set sizes were influenced by misleading feedback during an estimation
      task. We propose that subjects employ structure mappings for linking relatively
      large number words to set sizes, but rely chiefly on item-by-item associative
      mappings for smaller sets. These results indicate that both inference and
      association play important roles in mapping number words to approximate
      magnitudes.

PMID- 22963175
TI  - Breast feeding and early life immunomodulation.

PMID- 22963178
TI  - The use of explicitly correlated methods on XeF6 predicts a C3v minimum with a
      sterically active, free valence electron pair on Xe.
AB  - Explicitly correlated CCSD(T)-F12b calculations show that the lowest energy
      conformer of XeF(6) is the C(3v) structure with a stereoactive lone pair. The
      C(3v) structure is 1.08 kcal/mol below the C(2v) structure and 1.80 kcal/mol
      below the O(h) structure without vibrational corrections. The C(2v) conformer is
      a transition state connecting the different C(3v) minima on the pseudorotation
      potential energy surface, and the O(h) structure is a higher-order saddle point
      leading to the C(2v) transition states. The calculated vibrational frequencies
      for the C(3v) structure best fit the experimental frequencies. The calculated
      heats of formation for XeF(6), -62.1 +/- 1.4 kcal/mol at 0 K and -64.0 +/- 1.4
      kcal/mol at 298 K, are the best available values and show that there are serious
      issues with the experimental values. The results show that the explicitly
      correlated CCSD(T)-F12b method can be used to address important electronic
      structure issues with smaller basis sets.

PMID- 22963176
TI  - Are children with "pure" generalized anxiety disorder impaired? A comparison with
      comorbid and healthy children.
AB  - Despite the approach of the Diagnostic and Statistical Manual of Mental Disorders
      (5th ed.), generalized anxiety disorder (GAD) of childhood continues to face
      questions as to whether it should be considered a distinct clinical disorder. A
      potentially critical issue embedded in this debate involves the role of
      functional impairment which has yet to be demonstrated in children with "pure"
      GAD. Participants included 41 children between the ages of 6 and 11 years who met
      diagnostic criteria for primary GAD. Children with pure GAD (n = 17) were
      compared to children with comorbid GAD (n = 24) as well as a healthy control
      group (n = 20) in terms of clinician-rated severity and impairment and child
      reported adaptive functioning across four domains. On average, children with pure
      GAD were more likely to be male and younger than children with comorbid GAD.
      Based on traditional significance testing, global impairment was greater in the
      comorbid compared to pure GAD group, although functioning in both groups was in
      the "variable" range. Both clinical groups reported less adaptive family
      relationships than controls, whereas only the comorbid group reported lower
      levels of home-based functioning. Equivalence testing nonetheless indicated a
      lack of comparability (i.e., nonequivalence) across the three groups for each of
      the domains examined. Findings indicate children with pure GAD to be functionally
      impaired compared to their healthy peers, though not to the same extent as
      children with secondary psychiatric diagnoses. Child functioning within the
      family domain specifically may be among the most vulnerable when GAD is present.
      Results support consideration of childhood GAD as a distinct clinical disorder.

PMID- 22963179
TI  - Multi-scale finite element modelling at the posterior lumbar vertebra: analysis
      of pedicle stresses due to pars fracture.
AB  - Multi-scale finite element (FE) model is a cost-effective way to analyse stress
      response of micro-level structures to the changes in loading at macro-level. This
      study deals with the development of a multi-scale model of a human vertebra and
      stress changes in the pedicle at high resolution after a gross fracture at the
      posterior neural arch. Spondylolysis (pars fracture) is a painful condition
      occurring in the vertebral neural arch and common especially among the athletic
      young population. The fracture of the pars significantly alters load distribution
      and load transfer characteristics at the neural arch. Structural changes in the
      posterior vertebra due to the new loading patterns can trigger secondary
      complications. Clinical reports have shown the association of pedicle hypertrophy
      or pedicle fracture with unilateral pars fractures. However, the biomechanical
      consequences of pars fracture and its effect on the pedicle have never been
      studied in detail. Therefore, we prepared a multi-scale model of posterior
      vertebra with continuum laminar complex model combined with micro-FE model of a
      pedicle section. The results showed that stress at the contralateral pars and
      pedicle increased after unilateral pars fracture simulation. High-stress regions
      were found around the outer boundaries of the pedicle. This model and information
      are helpful in understanding the stress changes in the pedicle and can be used
      for adaptive remodelling studies. 

PMID- 22963180
TI  - Discordant parent reports of family functioning following childhood
      neuroblastoma: a report from the children's oncology group.
AB  - This study examined whether late effects and poor survivor quality of life (QOL)
      characterize discordant parent dyads and "unhealthy" family functioning in
      neuroblastoma survivors. Parents of 135 neuroblastoma survivors (78 two-parent
      dyads) completed measures of late effects and family functioning, and survivors
      completed the Pediatric Quality of Life Inventory 4.0 (PedsQL). Although average
      family functioning scores were "healthy," parent concordance was lower for family
      functioning than late effects reports. Parent concordance did not differ by late
      effects or QOL. Family functioning scores were poorer when survivors had more
      late effects and low physical QOL scores. Parent data should be considered
      separately when examining child cancer outcomes.

PMID- 22963181
TI  - Psychological distress among adolescents living with a parent with advanced
      cancer.
AB  - The objective of this exploratory study was to evaluate the impact of advanced
      parental cancer on adolescents' psychological status. A sample of 28 adolescents,
      having a parent with advanced cancer, was recruited and compared with a sample
      from the general population (N = 2,346). Late adolescents (age 15 to 18)
      experienced significantly more psychological distress than early adolescents (age
      12 to 14). Moreover, late adolescents experienced significantly higher
      psychological distress than the general population for the same age group, which
      was not the case for early adolescents. Implications for adolescents living in
      families touched by advanced cancer are discussed.

PMID- 22963182
TI  - Development of an educational intervention focused on sexuality for women with
      gynecological cancer.
AB  - The purpose of this article is to report on the development of an educational
      intervention that focuses on providing women with gynecological cancer
      information on sexuality. Intervention development was guided by the Medical
      Research Council framework for complex intervention development. A phased
      approach was taken to the design and evaluation of this complex intervention
      which included (1) an in-depth literature review, (2) selection of a theoretical
      framework, (3) a qualitative study, (4) development of intervention content and
      process, and (5) pilot testing of the intervention. The educational intervention
      consists of an information booklet combined with a verbal education session.
      Content of the intervention is guided by a conceptual framework of sexuality,
      whereas the intervention process is guided by andragogical principles and the
      PLISSIT model. Content validity was established by patient and expert review.

PMID- 22963183
TI  - Assessing the relationship between physical fitness activities, cognitive health,
      and quality of life among older cancer survivors.
AB  - Chemotherapy-related cognitive impairment, known as "chemobrain," has been
      described as a side effect of chemotherapy and is associated with cognitive
      changes on quality of life especially among older cancer survivors. This
      longitudinal feasibility study examined the relationship between physical
      fitness, cognitive health, and quality of life among two groups of older adults:
      those on chemotherapy, and those who have completed chemotherapy. To assess
      cognitive health, we used the Montreal Cognitive Assessment and demographic
      information from the Healthy Brain Questionnaire. For quality of life, we used
      the McGill Quality of Life assessment. Physical activity was assessed using
      Metabolic Equivalency Tasks from the Compendium of Physical Activities
      classification system. t-Tests and regression analyses indicated that at Time 1
      those on chemotherapy had lower cognitive health scores than those off
      chemotherapy. Yet at Time 2, as physical activities increased, cognitive health
      and quality of life improved for those on chemotherapy. However, those who had
      completed chemotherapy also benefited from an increase in physical activities
      over time. The results have implications for health care practitioners in
      oncology settings to better inform patients of cognitive challenges resulting
      from chemotherapy and the importance of participation in physical activities.
      Future research should compare different age groups among a larger sample.

PMID- 22963184
TI  - How social sharing and social support explain distress in breast cancer after
      surgery: the role of alexithymia.
AB  - Perceived social support has shown to be key to adjustment along the cancer
      trajectory, but results remain contradictory about the disclosure of the
      experience of the illness (social sharing) and may reflect the importance of
      patients characteristics. The authors explored the associations between social
      sharing, perceived social support, and emotional adjustment in nonmetastatic
      breast cancer patients and how alexithymia may impact these associations. One
      hundred and thirteen women with breast cancer from a cancer care center in
      Villejuif (France) were assessed after breast surgery. Participants completed
      measures of depression, negative affect, and alexithymia together with a self
      description of social sharing of their disease experience and perceived social
      support. Higher depression and negative affect were related to a high level of
      emotional sharing, a low satisfaction with confidant's reactions, and a high
      perceived negative support. In comparison with low-alexithymia patients, those
      with high alexithymia showed positive associations between negative emotional
      outcomes and (1) negative social support and (2) emotional sharing. These results
      suggest that the relationships between social sharing/support and emotional
      outcomes depend also on individual characteristics, such as alexithymia.
      Assessing perceived social support and alexithymia in cancer patients is useful
      to identify who might benefit from social sharing. Interventions could focus on
      helping the social network and environment to adjust to the socioemotional
      characteristics of breast cancer patients along the cancer trajectory.

PMID- 22963185
TI  - Children's positive dispositional attributes, parents' empathic responses, and
      children's responses to painful pediatric oncology treatment procedures.
AB  - Pain/distress during pediatric cancer treatments has substantial psychosocial
      consequences for children and families. The authors examined relationships
      between children's positive dispositional attributes, parents' empathic
      responses, and children's pain/distress responses to treatment procedures.
      Participants were 41 pediatric cancer patients and parents. Several weeks before
      treatment, parents rated children's resilience and positive dimensions of
      temperament. Parents' pretreatment empathic affective responses to their children
      were assessed. Children's pain/distress during treatments was rated by multiple
      independent raters. Children's resilience was significantly and positively
      associated with parents' empathic affective responses and negatively associated
      with children's pain/distress. Children's adaptability and attention focusing
      also showed positive relationships (p < 0.10) with parents' empathic responses.
      Parents' empathic responses mediated effects of children's resilience on
      children's pain/distress. Children's positive dispositional attributes influence
      their pain/distress during cancer treatments; however, these effects may be
      mediated by parents' empathic responses. These relationships provide critical
      understanding of the influence of parent-child relationships on coping with
      treatment.

PMID- 22963186
TI  - Oral cyclophosphamide without corticosteroids to treat mucous membrane
      pemphigoid.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) still represents a potentially life-
      and sight-threatening disease. Immunosuppressants, such as cyclophosphamide
      (CYC), are indicated for patients with severe and/or refractory MMP. OBJECTIVES:
      To evaluate the efficacy and safety of daily oral CYC without corticosteroids as
      therapy for severe MMP. METHODS: Thirteen patients with severe refractory MMP,
      who received oral CYC at an initial dose of 2 mg kg(-1) without corticosteroids,
      were retained. Previous treatments, for example dapsone, sulfasalazine or topical
      agents, were maintained during CYC treatment. Initial clinical severity and
      response to treatment were assessed by scoring. CYC was stopped after complete
      remission (CR), or when MMP progressed or lymphopenia (< 0.7 * 10(9) cells L(-1)
      ) occurred. RESULTS: After 52 weeks of CYC treatment, the overall response rate
      was 69% (9/13 patients) with a median time to disease control of 8 weeks (range 4
      52 weeks). Seven patients (54%) entered CR with a median time to CR of 24 weeks
      (range 16-52 weeks), all remaining in CR at week 52. The mean duration of CYC
      administration was 12 weeks (range 2-52 weeks). The most common side effect was
      lymphopenia (10/13 patients), which led to CYC withdrawal for six patients. No
      sepsis was observed. CONCLUSIONS: CYC without corticosteroids had rapid efficacy
      in patients with severe refractory MMP and was safe.

PMID- 22963187
TI  - A 3-dimensional view of access to licensed and subsidized medicines under single
      payer systems in the US, the UK, Australia and New Zealand.
AB  - INTRODUCTION: Patients' access to medicines can be profoundly affected by the
      decisions made by medicine licensing bodies and public reimbursement agencies.
      The present study compares access to licensed and subsidized medicines under a
      single-payer system in each of the US, the UK, Australia and New Zealand (NZ).
      These systems are the US Department of Veterans Affairs National Formulary
      (VANF), the UK NHS for England and Wales, Australian Pharmaceutical Benefits
      Scheme (PBS) and NZ's Pharmaceutical Management Agency (PHARMAC). The VANF, PBS
      and PHARMAC all use positive lists of medicines that are subsidized, along with
      pharmacoeconomic analysis and price negotiations with suppliers. The NHS uses a
      negative list of medicines that are not to be subsidized, along with
      pharmacoeconomic analysis of a small number of medicines and caps on
      manufacturers' profits. OBJECTIVE: Our objective was to compare licensed and
      subsidized medicines in terms of the following: (i) total numbers of entities
      (unique Anatomical Therapeutic Chemical [ATC] codes); (ii) times since first
      registration (age) of the entities; and (iii) numbers of innovative entities.
      METHODS: This was an observational study in order to test pre-defined hypotheses.
      All products listed in a major prescribing reference in each country were
      included in the study. All products were classified by ATC code and their
      registration dates recorded. Products were collapsed by ATC code to determine
      'best-case' licensing and subsidy for each entity, along with the date of first
      registration. Innovative entities selected for 'fast-track' approval by the US
      FDA or as a 'breakthrough or substantial improvement' by the Canadian Patented
      Medicines Prices Review Board were identified. Results were verified by a
      sensitivity analysis that excluded entities only available in injectable
      formulations (as these may not always be listed in general prescribing
      references), and by a parallel analysis done by active agent rather than ATC
      code. RESULTS: Of the 918 entities and 64 innovative entities licensed in the US,
      505 and 20, respectively, were subsidized by the VANF. In the UK, this was 1020
      and 58 (1016 and 58 NHS subsidized); in Australia, this was 879 and 49 (567 and
      30 PBS subsidized); and in NZ, this was 765 and 39 (503 and 19 PHARMAC
      subsidized). With the exception of the UK, entities licensed in the US were newer
      than elsewhere. The median ages were as follows: 6607 days in the US (VANF
      subsidized 8203 days; p < 0.001); 7319 days in the UK (NHS subsidized 7319 days;
      p = 0.903); 7795 days in Australia (PBS subsidized 8065 days; p = 0.406); and
      8936 days in NZ (PHARMAC subsidized 10 724 days; p < 0.001). NHS subsidized
      entities were newer than elsewhere. VANF and PHARMAC subsidized entities were
      significantly older than licensed entities in their respective countries.
      CONCLUSION: The single-payer systems examined differ in the number and age of
      licensed and subsidized entities, along with access to innovative entities. The
      NHS subsidized the most entities, the newest entities and the most innovative
      entities. NZ's PHARMAC system subsidized the fewest and oldest entities, and the
      fewest innovative entities. The VANF and PBS consistently fell between the other
      two systems in terms of the number of subsidized entities, age of subsidized
      entities and number of subsidized innovative entities.

PMID- 22963188
TI  - Inferential dependencies in causal inference: a comparison of belief-distribution
      and associative approaches.
AB  - Causal evidence is often ambiguous, and ambiguous evidence often gives rise to
      inferential dependencies, where learning whether one cue causes an effect leads
      the reasoner to make inferences about whether other cues cause the effect. There
      are 2 main approaches to explaining inferential dependencies. One approach,
      adopted by Bayesian and propositional models, distributes belief across multiple
      explanations, thereby representing ambiguity explicitly. The other approach,
      adopted by many associative models, posits within-compound associations-
      associations that form between potential causes--that, together with associations
      between causes and effects, support inferences about related cues. Although these
      fundamentally different approaches explain many of the same results in the causal
      literature, they can be distinguished, theoretically and experimentally. We
      present an analysis of the differences between these approaches and, through a
      series of experiments, demonstrate that models that distribute belief across
      multiple explanations provide a better characterization of human causal reasoning
      than models that adopt the associative approach.

PMID- 22963189
TI  - An electrophysiological signature of summed similarity in visual working memory.
AB  - Summed-similarity models of short-term item recognition posit that participants
      base their judgments of an item's prior occurrence on that item's summed
      similarity to the ensemble of items on the remembered list. We examined the
      neural predictions of these models in 3 short-term recognition memory experiments
      using electrocorticographic/depth electrode recordings and scalp
      electroencephalography. On each experimental trial, participants judged whether a
      test face had been among a small set of recently studied faces. Consistent with
      summed-similarity theory, participants' tendency to endorse a test item increased
      as a function of its summed similarity to the items on the just-studied list. To
      characterize this behavioral effect of summed similarity, we successfully fit a
      summed-similarity model to individual participant data from each experiment.
      Using the parameters determined from fitting the summed-similarity model to the
      behavioral data, we examined the relation between summed similarity and brain
      activity. We found that 4-9 Hz theta activity in the medial temporal lobe and 2-4
      Hz delta activity recorded from frontal and parietal cortices increased with
      summed similarity. These findings demonstrate direct neural correlates of the
      similarity computations that form the foundation of several major cognitive
      theories of human recognition memory.

PMID- 22963190
TI  - Molecular aspects of vitamin D anticancer activity.
AB  - Environment may influence the development and prevention of cancer. Calcitriol
      has been associated with calcium homeostasis regulation. Many epidemiological,
      biochemical, and genetic studies have shown non-classic effects of vitamin D,
      such as its involvement in the progression of different cancers. Although vitamin
      D induces cellular arrest, triggers apoptotic pathways, inhibits angiogenesis,
      and alters cellular adhesion, the precise mechanisms of its action are still not
      completely established. This article will present a revision about the molecular
      aspects proposed to be involved in the anticancer action of calcitriol. Adequate
      levels of vitamin D to prevent cancer development will also be discussed.

PMID- 22963192
TI  - Thermal decomposition and recovery behaviors of layered gadolinium
      hydroxychloride.
AB  - The thermal behavior of gadolinium hydroxychloride (Gd(2)(OH)(5)Cl.nH(2)O, LGdH)
      has been closely studied to provide the important factors that should be
      considered for its high temperature applications. Combined analyses of
      thermogravimetry-differential scanning calorimetry-mass spectrometry (TG-DSC-MS)
      showed that, under atmospheric air with a considerable amount of water, the
      decomposition of LGdH to Gd(2)O(3) is completed at 1050  degrees C. However, in
      either dry air or Ar gas, the transformation continued up to around 1300  degrees
      C. Thus, the thermal decomposition of LGdH was more influenced by H(2)O than by
      O(2). FT-IR spectra and X-ray diffraction (XRD) patterns were used to study LGdHs
      calcined at high temperatures (up to at least 600  degrees C). Calcined LGdH's
      ability to intercalate anions into the interlayer space could be recovered by the
      reconstruction of intralayer structure through rehydration and rehydroxylation.
      These processes were significantly accelerated at elevated temperatures. The
      recovery behavior of LGdH was examined in different anionic solutions at
      different temperatures.

PMID- 22963193
TI  - Rearranged benzophenones and prenylated xanthones from Garcinia propinqua twigs.
AB  - The first phytochemical investigation of Garcinia propinqua has led to the
      isolation and identification of three new compounds, including two rearranged
      benzophenones, doitunggarcinones A (1) and B (2), and a xanthone,
      doitunggarcinone C (3), together with seven known compounds (4-10). The
      structures of 1-3 were elucidated on the basis of spectroscopic methods,
      including UV, IR, NMR, and MS. The antibacterial activity of the 10 isolates was
      evaluated against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292,
      Staphylococcus aureus TISTR 1466, and methicillin-resistant Staphylococcus aureus
      (MRSA) SK1.

PMID- 22963191
TI  - Kalanchoe tubiflora extract inhibits cell proliferation by affecting the mitotic
      apparatus.
AB  - BACKGROUND: Kalanchoe tubiflora (KT) is a succulent plant native to Madagascar,
      and is commonly used as a medicinal agent in Southern Brazil. The underlying
      mechanisms of tumor suppression are largely unexplored. METHODS: Cell viability
      and wound-healing were analyzed by MTT assay and scratch assay respectively. Cell
      cycle profiles were analyzed by FACS. Mitotic defects were analyzed by indirect
      immunofluoresence images. RESULTS: An n-Butanol-soluble fraction of KT (KT-NB)
      was able to inhibit cell proliferation. After a 48 h treatment with 6.75 MUg/ml
      of KT, the cell viability was less than 50% of controls, and was further reduced
      to less than 10% at higher concentrations. KT-NB also induced an accumulation of
      cells in the G2/M phase of the cell cycle as well as an increased level of cells
      in the subG1 phase. Instead of disrupting the microtubule network of interphase
      cells, KT-NB reduced cell viability by inducing multipolar spindles and defects
      in chromosome alignment. KT-NB inhibits cell proliferation and reduces cell
      viability by two mechanisms that are exclusively involved with cell division:
      first by inducing multipolarity; second by disrupting chromosome alignment during
      metaphase. CONCLUSION: KT-NB reduced cell viability by exclusively affecting
      formation of the proper structure of the mitotic apparatus. This is the main idea
      of the new generation of anti-mitotic agents. All together, KT-NB has sufficient
      potential to warrant further investigation as a potential new anticancer agent
      candidate.

PMID- 22963194
TI  - Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in
      patients with idiopathic membranous nephropathy: an observational study.
AB  - BACKGROUND: Patients with nephrotic syndrome are at an increased risk of
      thromboembolic events (TEs). However, this association has not been thoroughly
      investigated in adult patients with idiopathic membranous nephropathy (IMN).
      METHODS: A retrospective analysis of all 101 consecutive adult patients with MN
      diagnosed at our centre during 1995 to 2008 was performed. Pertinent data
      including thromboembolic events and the risk factors for TEs were recorded.
      RESULTS: The cohort was followed for 7.2 +/- 3 years. Out of 78 patients with
      IMN, 15 (19.2%) had at least one TE. No TEs occurred six months after diagnosis.
      The incidence of TEs in the first 6 months of diagnosis was 7.69% (95%CI, 2.5
      17.0) and all patients except one had venous TEs. At the time of diagnosis of MN,
      the patients with TEs had lower serum albumin (1.9 +/- 0.5 vs. 2.4 +/- 0.4 g/dl,
      TE vs. no TE; p < 0.01) and greater serum cholesterol (414 +/- 124 vs. 317 +/-
      108 mg/dl, TE vs. no TE; p = 0.01) and 24-h proteinuria (10.7 +/- 3 vs. 7.1 +/- 4
      g, TE vs. no TE; p < 0.01). Multivariate logistic regression adjusted for age,
      sex, cholesterol and creatinine revealed, an odds ratio of 0.8 (95% CI 0.7 -
      0.96; p = 0.01) for every one g/dl increase in baseline serum albumin and, an
      odds ratio of 1.3 (95% CI 1.05-1.58; p = 0.01) for one gram increase in 24-h
      proteinuria, for TEs. CONCLUSIONS: Our study finding confirms IMN as a
      prothrombotic state particularly in the first six months of diagnosis.
      Proteinuria, in addition to hypoalbuminemia, is a risk factor for TEs. These
      results have important implications for clinical care of patients with IMN,
      particularly with regards to initiation and duration of prophylactic
      anticoagulation.

PMID- 22963195
TI  - Neural correlates of high frequency repetitive transcranial magnetic stimulation
      improvement in post-stroke non-fluent aphasia: a case study.
AB  - Damage to the left inferior frontal gyrus (lIFG) affects language and can cause
      aphasia in stroke. Following left hemisphere damage it has been suggested that
      the homologue area in the right hemisphere compensates for lost functions. An
      increasing number of studies have demonstrated that inhibitory 1-Hz repetitive
      transcranial magnetic stimulation (rTMS) targeting the right IFG can be useful
      for enhancing recovery in aphasic patients. In the present study we applied
      activating high frequency (10-Hz) rTMS, which increases cortical excitability, to
      the damaged lIFG daily for 3 weeks. Pre- and post-TMS EEG are performed, as well
      as language function assessments with the Aachener Aphasia Test Battery. Results
      demonstrate a decrease in rIFG activity post rTMS and normalization for the lIFG
      for beta3 frequency band. Also increased activity was in the right supplementary
      motor area for beta3 frequency band. In comparison to pre-TMS the aphasic patient
      improved on repetition tests, for naming and comprehension. After rTMS increased
      functional connectivity was shown in comparison to before between the lIFG and
      the rIFG for theta and beta3 frequency band. This case report suggests that 10 Hz
      rTMS of the lIFG can normalize activity in the lIFG and right IFG possibly
      mediated via altered functional connectivity. 

PMID- 22963196
TI  - Synchronized aromaticity as an enthalpic driving force for the aromatic Cope
      rearrangement.
AB  - We report herein experimental and theoretical evidence for an aromatic Cope
      rearrangement. Along with several successful examples, our data include the first
      isolation and full characterization of the putative intermediate that is formed
      immediately after the initial [3,3] sigmatropic rearrangement. Calculations at
      the B3LYP/6-31G(d) level of theory predict reaction energy barriers in the range
      22-23 kcal/mol for the [3,3]-rearrangement consistent with the exceptionally mild
      reaction conditions for these reactions. The experimental and computational
      results support a significant enthalpic contribution of the concomitant pyrazole
      ring formation that serves as both a kinetic and thermodynamic driving force for
      the aromatic Cope rearrangement.

PMID- 22963198
TI  - Effect of nuclear motion on molecular high order harmonic pump probe
      spectroscopy.
AB  - We study pump-probe schemes for the real time observation of electronic motion on
      attosecond time scale in the molecular ion H(2)(+) and its heavier isotope
      T(2)(+) while these molecules dissociate on femtosecond time scale by solving
      numerically the non-Born-Oppenheimer time-dependent Schrodinger equation. The UV
      pump laser pulse prepares a coherent superposition of the three lowest lying
      quantum states and the time-delayed mid-infrared, intense few-femtosecond probe
      pulse subsequently generates molecular high-order harmonics (MHOHG) from this
      coherent electron-nuclear wavepacket (CENWP). Varying the pump-probe time delay
      by a few hundreds of attoseconds, the MHOHG signal intensity is shown to vary by
      orders of magnitude. Due to nuclear movement, the coherence of these two upper
      states and the ground state is lost after a few femtoseconds and the MHOHG
      intensity variations as function of pump-probe delay time are shown to be equal
      to the period of electron oscillation in the coherent superposition of the two
      upper dissociative quantum states. Although this electron oscillation period and
      hence the periodicity of the harmonic spectra are quite constant over a wide
      range of internuclear distances, a strong signature of nuclear motion is seen in
      the actual shapes and ways in which these spectra change as a function of pump
      probe delay time, which is illustrated by comparison of the MHOHG spectra
      generated by the two isotopes H(2)(+) and T(2)(+). Two different regimes
      corresponding roughly to internuclear distances R < 4a(0) and R > 4a(0) are
      identified: For R < 4a(0), the intensity of a whole range of frequencies in the
      plateau region is decreased by orders of magnitude when the delay time is changed
      by a few hundred attoseconds whereas in the cutoff region the peaks in the MHOHG
      spectra are red-shifted with increasing pump-probe time delay. For R > 4a(0), on
      the other hand, the peaks both in the cutoff and plateau region are red-shifted
      with increasing delay times with only slight variations in the peak intensities.
      A time-frequency analysis shows that in the case of a two-cycle probe pulse the
      sole contribution of one long and associated short trajectory correlates with the
      attenuation of a whole range of frequencies in the plateau region for R < 4a(0)
      whereas the observed red shift for R > 4a(0), even in the plateau region,
      correlates with a single electron return within one-half laser cycle.

PMID- 22963197
TI  - Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor
      immunoreactive lamina I projection neurons in rat spinal cord.
AB  - BACKGROUND: Pain-related (nociceptive) information is carried from the periphery
      to the dorsal horn of the spinal cord mostly by two populations of small diameter
      primary afferents, the peptidergic and the non-peptidergic. The peptidergic
      population expresses neuropeptides, such as substance P and calcitonin gene
      related peptide, while the non-peptidergic fibers are devoid of neuropeptides,
      express the purinergic receptor P2X3, and bind the isolectin B4 (IB4). Although
      it has been known for some time that in rat the peptidergic afferents terminate
      mostly in lamina I and outer lamina II and non-peptidergic afferents in inner
      lamina II, the extent of the termination of the latter population in lamina I was
      never investigated as it was considered as very minor. Because our preliminary
      evidence suggested otherwise, we decided to re-examine the termination of non
      peptidergic afferents in lamina I, in particular with regards to their
      innervation of projection neurons expressing substance P receptors (NK-1r). We
      used retrograde labeling of neurons from the parabrachial nucleus combined with
      lectin IB4 binding and immunocytochemistry. Samples were examined by confocal and
      electron microscopy. RESULTS: By confocal microscopy, we studied the termination
      of non-peptidergic afferents in lamina I using IB4 binding and P2X3
      immunoreactivity as markers, in relation to CGRP immunoreactivy, a marker of
      peptidergic afferents. The number of IB4 or P2X3-labeled fibers in lamina I was
      higher than previously thought, although they were less abundant than CGRP
      labeled afferents. There were very few fibers double-labeled for CGRP and either
      P2X3 or IB4. We found a considerable number of IB4-positive fiber varicosities in
      close apposition to NK-1r-positive lamina I projection neurons, which were
      distinct from peptidergic varicosities. Furthermore, we confirmed at the
      ultrastructural level that there were bona fide synapses between P2X3
      immunoreactive non-peptidergic boutons and neurokinin-1 receptor-positive lamina
      I dendrites. CONCLUSIONS: These results indicate the presence of direct
      innervation by non-peptidergic nociceptive afferents of lamina I projection
      neurons expressing NK-1r. Further investigations are needed to better understand
      the role of these connections in physiological conditions and chronic pain
      states.

PMID- 22963199
TI  - Recovery of viable cyanophages from the sediments of a eutrophic lake at decadal
      timescales.
AB  - Cyanobacteria and their associated viruses (cyanophages) are abundant throughout
      the world in both marine and freshwater environments. The predator-prey
      relationship influences population dynamics within these ecosystems and
      facilitates the co-evolution of both organisms. Evidence of the close-linked
      interactions between cyanobacteria and viruses has been found extensively
      throughout marine biomes, but freshwater systems are less well studied. Eutrophic
      lake sediments potentially allow the preservation of cyanophages. If historic
      cyanophages could be isolated, they could provide insights into the evolution,
      biology and population dynamics over defined timescales. To determine whether
      viable phages are present in this environment, sectioned sediment cores (~ 50 cm
      in length) were taken from a eutrophic, stratifying lake (Rostherne Mere,
      Cheshire, UK). They were examined under the transmission electron microscope, and
      phages were isolated on two Microcystis strains PCC 7820 and BC 84/1. Viable
      phages were recovered from ~ 33- and ~ 50-year-old sediments. This is the first
      known study to investigate the viability of freshwater cyanophages recovered from
      dated lake sediments.

PMID- 22963200
TI  - Evaluation of canine prostate intrafractional motion using serial cone beam
      computed tomography imaging.
AB  - This study used kilovoltage (kV) cone beam computed tomography (CBCT) imaging to
      characterize canine intrafractional prostate motion during hypofractionated
      stereotactic radiotherapy treatment. Serial CBCT images taken just prior to
      initiating treatment, and at several times during the treatment session, were
      acquired throughout the course of treatment for canine patients. All patients
      were immobilized in dorsal recumbency while using an air-inflated rectal balloon.
      For each treatment session, rigid registration of intrafraction CBCT images with
      the interfraction CBCT used for setup verification was performed. Contours of the
      prostate and urethra were drawn on each CBCT image set and the center of mass for
      each structure was evaluated as a function of time. A total of seven canine
      patients was included in the study, resulting in 41 CBCT images collected during
      a total of 12 treatment sessions. Over 70% of our data were collected for CBCTs
      taken between 20 and 51 min after final patient setup was complete. The mean
      intrafraction movement in a single direction for the prostate and urethra was
      <=0.14 mm and <=0.22 mm, respectively. The maximum intrafraction movement for the
      prostate and urethra was <= 1.60 mm and <= 2.00 mm, respectively. The maximum
      variability in intrafraction movement for the prostate and urethra, as defined by
      two standard deviations, was <=1.40 mm and <=1.50 mm, respectively. Minimal
      intrafraction variability using appropriate patient positioning and rectal
      balloon, combined with kV CBCT image-guided radiation therapy tools to account
      for interfraction changes, permit accurate and precise targeting of structures of
      interest.

PMID- 22963201
TI  - Aryl- and heteroaryl-thiosemicarbazone derivatives and their metal complexes: a
      pharmacological template.
AB  - In this review, we discuss the current patents concerning aryl/heteroaryl
      thiosemicarbazone derivatives as regards to their activities and properties,
      including coordination (chelation) properties. The mode of action of the
      aryl/heteroaryl thiosemicarbazone derivatives involves metal coordination with
      proteins or biological fluids that have metal ions in their structure.
      Additionally, these molecules can also form multiple hydrogen bonds through their
      (thio) amide and N3 nitrogen that ensure a strong interaction with the receptor.
      In some cases, strong pi-pi interactions can be observed too. Special attention
      is given to pyridyl, bis-pyridyl, benzoylpyridyl and isatin thiosemicarbazone
      derivatives that exhibit significant anticancer, antiviral and other activities
      in free and in metal complexed forms. This key biological role is often related
      with their capability to inhibit the enzyme ribonucleotide reductase, similar to
      what is observed with potent anticancer drugs such as Triapine and methisazone.
      Recent studies have revealed that thiosemicarbazone can also inhibit
      topoisomerase II alpha enzyme. Thiosemicarbazone derivatives form coordination
      complex with various metals such as Zn, Cu, Fe, Co, Ni, Pt, Pd, etc., and these
      complexes provide better activities than the free thiosemicarbazones. Recent
      patents show that the controlled or sustained release dosage form of the
      thiosemicarbazone derivatives along with ionizing radiations is used for the
      treatment of proliferative diseases (US20110152281, US20110245304,
      US20120172217).

PMID- 22963202
TI  - Presentation of two patients with malignant granulosa cell tumors, with a review
      of the literature.
AB  - Granulosa cell tumors (GCTs) of the ovary account for 2 to 5 of ovarian
      malignancies. We present two patients with malignant ovarian adult GCT. In one
      patient, a combination of bleomycin, etoposide, and cisplatin was effective after
      initial surgery for malignant GCT. In the other, an aromatase inhibitor was
      effective for recurrent malignant GCT. We also review the literature for further
      management of this tumor. Because GCT of the ovary is rare, it will be necessary
      to elucidate the clinical phenotype and establish treatment protocols by
      accumulating and analyzing more patients.

PMID- 22963204
TI  - Asymmetry in the dorsolateral prefrontal cortex and aggressive behavior: a
      continuous theta-burst magnetic stimulation study.
AB  - Aggressive behavior is aimed at causing damage or pain to another individual.
      Aggression has been associated with structural and functional deficits in
      numerous brain areas, including the dorsolateral region of the prefrontal cortex
      (DLPFC), typically related to inhibition and impulse control. In this study, we
      used inhibitory continuous theta-burst magnetic stimulation (cTBS) to explore the
      role of the right and left DLPFC in aggression. Sixteen healthy right-handed
      volunteers underwent two sessions involving random, real and sham, right and left
      DLPFC stimulations. These sessions were followed by the Social Orientation
      Paradigm (SOP), a monetary task that was specially designed to assess
      participants' aggressive tendencies by measuring the patterns of their reactive
      aggression (a response to a perceived provocation) and proactive aggression (an
      aggressive act with goal-oriented purposes). Results indicate that using cTBS to
      target the left DLPFC was associated with a greater increase in aggressive
      responses than right DLPFC stimulation. This pattern of results was found for
      both reactive and proactive types of aggressive reactions. It is concluded that
      DLPFC asymmetry is involved in modulating reactive and proactive aggression. Our
      results are in line with recent studies suggesting that the left DLPFC plays a
      major role in aggressive behavior.

PMID- 22963203
TI  - Insights into mRNP biogenesis provided by new genetic interactions among export
      and transcription factors.
AB  - BACKGROUND: The various steps of mRNP biogenesis (transcription, processing and
      export) are interconnected. It has been shown that the transcription machinery
      plays a pivotal role in mRNP assembly, since several mRNA export factors are
      recruited during transcription and physically interact with components of the
      transcription machinery. Although the shuttling DEAD-box protein Dbp5p is
      concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated
      that it interacts physically and genetically with factors involved in
      transcription initiation. RESULTS: We investigated the effect of mutations
      affecting various components of the transcription initiation apparatus on the
      phenotypes of mRNA export mutant strains. Our results show that growth and mRNA
      export defects of dbp5 and mex67 mutant strains can be suppressed by mutation of
      specific transcription initiation components, but suppression was not observed
      for mutants acting in the very first steps of the pre-initiation complex (PIC)
      formation. CONCLUSIONS: Our results indicate that mere reduction in the amount of
      mRNP produced is not sufficient to suppress the defects caused by a defective
      mRNA export factor. Suppression occurs only with mutants affecting events within
      a narrow window of the mRNP biogenesis process. We propose that reducing the
      speed with which transcription converts from initiation and promoter clearance to
      elongation may have a positive effect on mRNP formation by permitting more
      effective recruitment of partially-functional mRNP proteins to the nascent mRNP.

PMID- 22963205
TI  - Escherichia coli and Enterococcus spp. in rainwater tank samples: comparison of
      culture-based methods and 23S rRNA gene quantitative PCR assays.
AB  - In this study, culture-based methods and quantitative PCR (qPCR) assays were
      compared with each other for the measurement of  Escherichia coli  and 
      Enterococcus  spp. in water samples collected from rainwater tanks in Southeast
      Queensland, Australia. Among the 50 rainwater tank samples tested, 26 (52%) and
      46 (92%) samples yielded  E. coli  numbers as measured by EPA Method 1603 and E.
      coli 23S rRNA gene qPCR assay, respectively. Similarly, 49 (98%) and 47 (94%)
      samples yielded  Enterococcus  spp. numbers as measured by EPA Method 1600 and 
      Enterococcus  spp. 23S rRNA gene qPCR assay, respectively. The mean  E. coli 
      (2.49 +/- 0.85) log(10) and  Enterococcus  spp. (2.72 +/- 0.32) log(10) numbers
      as measured by qPCR assays were significantly (P < 0001) different than  E. coli 
      (0.91 +/- 0.80) log(10) and  Enterococcus  spp. (1.86 +/- 0.60) log(10) numbers
      as measured by culture-based method. Weak but significant correlations were
      observed between both EPA Method 1603 and the  E. coli  qPCR assay (r = 0.47, P =
      0.0009), and EPA Method 1600 and the  Enterococcus  spp. qPCR assay (r = 0.42, P
      = 0.002). Good qualitative agreement was found between the culture-based method
      and the  Enterococcus  spp. qPCR assay in terms of detecting fecal pollution in
      water samples from the studied rainwater tanks. More research studies, however,
      are needed to shed some light on the discrepancies associated with the culture
      based methods and qPCR assays for measuring fecal indicator bacteria.

PMID- 22963206
TI  - New insights into childhood Vernal keratoconjunctivitis-associated factors.
AB  - The purpose of this study was to test for detectable serum levels of antibodies
      usually associated with immune-related diseases in children with Vernal
      keratoconjunctivitis (VKC) and seek for their family history of allergies and
      autoimmune disorders. The association of human leukocyte antigens (HLA) with VKC
      was also investigated. We enrolled 181 VKC children and assessed total and
      specific IgE, antithyroglobulin (AbTG), antithyroidperoxidase (AbTPO),
      antitransglutaminase (tTG), and antinuclear antibodies (ANA) by standard
      procedures. Class I and II HLA typing was also carried out following standard
      protocols, and it was compared with that of healthy subjects. Patients were
      positive for AbTG (22%), AbTPO (14.6%), and ANA (15.8%), and AbTG positivity was
      associated with VKC severity (mean ocular score +/- SD positive vs. negative:
      6.56 +/- 2.1 vs. 4.82 +/- 2.1; p = 0.03). We found that 12.2% of VKC cases had a
      positive family history for psoriasis, 6.4% for other cases of VKC, and 5.2% for
      thyroiditis, while 50.2% of them were atopic. The expression of HLA class I B37
      was significantly higher in VKC patients than in controls (7.1% vs. 2.1%, p =
      0.04), although not confirmed after multiple antigens testing analysis. Our study
      suggests a role of common components associated with immune-based diseases in the
      clinical expression of VKC.

PMID- 22963208
TI  - Novel treatment using thioglycolic acid for pincer nails.
AB  - The authors developed a novel treatment using thioglycolic acid (TGA) to
      chemically soften pincer nails. The objective was to describe a new treatment
      method for pincer nails by applying TGA to soften the nail and then fix it in the
      correct position. A total of 104 patients (nine men and 95 women; mean age, 56
      years) with 106 pincer nails underwent our treatment. A small hole was made on
      the markedly incurvated side of the pincer nail, and a super-elastic wire was
      inserted into the hole and bent backwards; 5% TGA was then applied for 6-7 h
      prior to reduction. Favorable reduction was achieved in 66% of patients within 1
      day of the procedure, in 30% within 2-4 days and in 4% 5 days or more later. No
      patient required surgery. No post-procedure infection, rash, continuous pain or
      nail cut out was evident. In eight cases, recurrences of nail deformity were
      observed within the 1-year follow-up period. Our novel method, which consists of
      administrating TGA via a hole in the nail plate, is a useful treatment for pincer
      nails.

PMID- 22963209
TI  - CCR has impact.

PMID- 22963207
TI  - Longitudinal examination of PTSD symptoms and problematic alcohol use as risk
      factors for adolescent victimization.
AB  - The current study examined associations between posttraumatic stress disorder
      (PTSD) symptoms and future interpersonal victimization among adolescents, after
      accounting for the impact of early victimization exposure, gender, ethnicity, and
      household income. In addition, problematic alcohol use was tested as a mediator
      of the relation between PTSD symptoms and subsequent victimization. Participants
      included a national longitudinal sample of adolescents (N = 3,604) who were ages
      12 to 17 at the initial assessment: 50% were male, and 67% were White, 16%
      African American, and 12% Hispanic. Cohort-sequential latent growth curve
      modeling was used to examine associations among the study variables. Baseline
      PTSD symptoms significantly predicted age-related increases in interpersonal
      victimization, even after accounting for the effects of earlier victimization
      experiences. In addition, alcohol problems emerged as a partial mediator of this
      relation, such that one fourth to one third of the effect of PTSD symptoms on
      future victimization was attributable to the impact of PTSD symptoms on alcohol
      problems (which, in turn, predicted additional victimization risk). Collectively,
      the full model accounted for more than half of the variance in age-related
      increases in interpersonal victimization among youth. Results indicate that PTSD
      symptoms serve as a risk factor for subsequent victimization among adolescents,
      over and above the risk conferred by prior victimization. This increased risk
      occurred both independently and through the impact of PTSD symptoms on
      problematic alcohol use. Based on these findings, it is hypothesized that the
      likelihood of repeated victimization among youth might be reduced through early
      detection and treatment of these clinical problems.

PMID- 22963210
TI  - Normothermic extracorporeal perfusion of isolated porcine liver after warm
      ischaemia: a preliminary report.
AB  - Liver transplantation is a major life-saving procedure, and donation after
      cardiac death (DCD) has increased the pool of potential liver donors. However,
      DCD livers are at increased risk of primary graft dysfunction and biliary tract
      ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the
      ability to protect, evaluate and, in future, transplant DCD livers. We conducted
      proof-of-concept experiments using a DCD model in the pig to assess the short
      term (4 hours) feasibility and functional efficacy of NELP. Using extracorporeal
      membrane oxygenation, parenteral nutrition, separate hepatic artery and portal
      vein perfusion, and physiological perfusion pressures, we achieved NELP and
      evidence of function (bile production, paracetamol removal, maintenance of normal
      ammonia and lactate levels) for 4 hours in pig livers subjected to 15 and 30
      minutes of cardiac arrest before explantation. Our experiments justify further
      investigations of the feasibility and efficacy of human DCD liver preservation by
      ex-vivo perfusion.

PMID- 22963211
TI  - Accessibility of the Australian population to an ICU, and of ICUs to each other.
AB  - OBJECTIVE: To use a geographic information system to qualitatively and
      quantitatively illustrate the geospatial relationship of the Australian
      population to intensive care resources. DESIGN, SETTING AND PARTICIPANTS:
      Intensive care unit data were sourced from the Australian and New Zealand
      Intensive Care Society Centre for Outcome and Resource Evaluation critical care
      resources survey (2007-2008) and adult patient database (2002-2008), and postcode
      data (2006) from the Australian Bureau of Statistics. Remoteness was classified
      within remoteness categories and the Accessibility/Remoteness Index of Australia
      Plus. Distance was the difference between two postcode's centroids. RESULTS:
      Ninety-one public ICUs were identified. Of these, 50 (54.9%) were in a major
      city, 24 (26.4%) were inner regional, 15 (16.5%) were outer regional, one (1.1%)
      was remote and one (1.1%) was very remote, compared with 64.2%, 20.8%, 11.7%,
      1.9% and 1.4% of the population, respectively (P = 0.324). Median population
      distance to the closest ICU was 35.9 km and closest Level 3 ICU was 54.8 km. This
      varied by state/territory, ranging from 7.6 km to the closest ICU for the
      Australian Capital Territory to 161.7 km for Western Australia. Overall, 84.8% of
      the Australian population were 0-50 km from an ICU, 12.9% were 51-300km, 2.3%
      were 301-1500 km, and 0.01% were > 1500km. This varied among the
      states/territories. A Level 3 ICU was the closest ICU for 65.4% of the
      population, a Level 2 for 27.6% and a Level 1 for 7%. Median distance between any
      two ICUs was 21.1 km. Generally, the distance between Level 3 ICUs was shorter
      than the distance to a Level 1 or Level 2 ICU. CONCLUSIONS: The distribution of
      Australian ICUs and the Australian population was similar. However, accessibility
      varied by state/territory.

PMID- 22963212
TI  - Development and evaluation of an influenza pandemic intensive care unit triage
      protocol.
AB  - OBJECTIVES: To develop an influenza pandemic ICU triage (iPIT) protocol that
      excludes patients with the highest and lowest predicted mortality rates, and to
      determine the increase in ICU bed availability that would result. DESIGN AND
      SETTING: Post-hoc analysis of a study evaluating two triage protocols, designed
      to determine which patients should be excluded from access to ICU resources
      during an influenza pandemic. ICU mortality rates were determined for the
      individual triage criteria in the protocols and included criteria based on the
      Sequential Organ Failure Assessment (SOFA) score. Criteria resulting in mortality
      rates outside the 25th and 75th percentiles were used as exclusion criteria in a
      new iPIT-1 protocol. The SOFA threshold component was modified further and
      reported as iPIT-2 and iPIT-3. MAIN OUTCOME MEASURE: Increase in ICU bed
      availability. RESULTS: The 25th and 75th percentiles for ICU mortality were 8.3%
      and 35.2%, respectively. Applying the iPIT-1 protocol resulted in an increase in
      ICU bed availability at admission of 71.7% +/- 0.6%. Decreasing the lower SOFA
      score exclusion criteria to <=6 (iPIT-2) and <=4 (iPIT-3) resulted in an increase
      in ICU bed availability at admission of 66.9% +/- 0.6% and 59.4 +/- 0.7%,
      respectively (P < 0.001). CONCLUSION: The iPIT protocol excludes patients with
      the lowest and highest ICU mortality, and provides increases in ICU bed
      availability. Adjusting the lower SOFA score exclusion limit provides a method of
      escalation or de- escalation to cope with demand.

PMID- 22963213
TI  - Direct and delayed admission to an intensive care or high dependency unit
      following discharge from the emergency department: associated patient
      characteristics and hospital outcomes.
AB  - OBJECTIVE: To compare patients admitted from the emergency department (ED)
      directly to a ward (EDWard), the intensive care unit (EDICU) or stepdown (high
      dependency) unit (EDSDU) with patients admitted via the ED, but whose admission
      to an ICU (EDWardICU) or SDU (EDWardSDU) was preceded by a ward stay. DESIGN,
      SETTING AND PARTICIPANTS: Administrative and clinical data linkage; 650-bed,
      tertiary referral hospital, whose ED has about 60 000 patient presentations per
      annum; adult patients admitted via the ED to a ward, ICU or SDU and whose ED
      length of stay (LOS) was < 24 h. MAIN OUTCOME MEASURE: Hospital outcome and stay.
      RESULTS: From January 2004 to December 2007, there were 43 484 patients, of whom
      40 609 (93.4%) were EDWard, 1020 (2.3%) were EDICU, 873 (2.0%) were EDSDU, 503
      (1.2%) were EDWardSDU, and 479 (1.1%) were EDWardICU. Hospital mortality for
      EDWardICU patients exceeded that of EDICU patients (34.9% v 23.3%; P < 0.01), as
      did EDWardSDU exceed EDSDU (12.3% v 7.8%; P < 0.01). Median ward stay for
      EDWardICU patients was 47 h 37 min (IQR, 14 h 48 min - 131 h 53 min) and for
      EDWardSDU patients, 46 h 18min (IQR, 18h 28 min - 140h 12 min) (P=0.75). Compared
      with patients admitted to the ICU from the operating theatre, EDWardICU patients
      had a longer median ward stay (58 h 35 min v 34 h 36 min; P = 0.03) and hospital
      mortality (42.8% v 20.2%; P < 0.01). CONCLUSION: Patients discharged from the ED
      to a general ward and subsequently to an ICU or SDU had a mortality that exceeded
      that of ED patients admitted directly to the ICU or SDU. Further investigations
      are warranted to explain this excess mortality and ascertain the extent of
      potential preventability.

PMID- 22963214
TI  - Nosocomial infections in a cohort of extracorporeal life support patients.
AB  - OBJECTIVES: To examine nosocomial infections in a cohort of patients receiving
      extracorporeal life support (ECLS) at our institution and to identify the types
      of infections, impact of prophylaxis, and any apparent risk factors for
      infection. METHODS: In a retrospective cohort study, we examined the records of
      all patients who received ECLS at our institution between August 2009 and March
      2011. A prospective, daily, multidisciplinary assessment of all microbiological
      issues in these patients was carried out, including assessment of microbiological
      culture positivity and clinical evidence of infection. The results of these
      assessments were analysed in relation to HELICS (Hospital in Europe Link for
      Infection Control through Surveillance) and CDC (Centers for Disease Control and
      Prevention) diagnostic criteria. The use of antimicrobials in these patients was
      also assessed, as well as the overall bloodstream infection rate in ICU patients.
      RESULTS: Seventeen patients received ECLS during the study period, with a total
      of 445 ECLS days. Of these patients, 13 received respiratory (venovenous) ECLS
      and four received cardiac (venoarterial) ECLS. There were 17 infections in the
      cohort: 11 ventilator-associated pneumonias; four bloodstream infections (likely
      all catheter related, yielding a rate of 9.0 infections/1000 ECLS days); one skin
      and soft tissue infection; and one urinary tract infection. The bloodstream
      infection rate in the ICU population as a whole was 9.30/1000 bed-days in 2009
      and 7.21/1000 bed-days in 2010. Resistant organisms were identified in 3/17
      infections: one methicillin-resistant Staphylococcus aureus, one multidrug
      resistant strain of Pseudomonas and one extended-spectrum Beta-lactamase
      producing Escherichia coli. The median time to acquiring nosocomial infection was
      25 days (interquartile range, 13-33 days). The first four ECLS patients received
      antibacterial (vancomycin) and antifungal (caspofungin) prophylaxis for the
      duration of ECLS, whereas the later cohort of 13 did not. In patients who
      received prophylactic antimicrobials, the defined daily dose (DDD) per 100 ECLS
      days was 49.54 for vancomycin and 49.63 for meropenem. In patients who did not
      receive prophylaxis, the corresponding DDDs were 25.31 and 37.73, respectively.
      In ICU patients overall, the DDD per 100 bed-days over the same time period was
      13.60 for vancomycin and 19.75 for meropenem. There were 21/445 ECLS days on
      which antimicrobials were not used. CONCLUSION: Although ECLS patients are at
      high risk of acquiring nosocomial infections, the infection rate in our cohort
      was low. The bloodstream infection rate compared favourably with previously
      published rates, and was comparable with the bloodstream infection rate among ICU
      patients as a whole over the same time period. Increased duration of ECLS in this
      cohort may correlate with an increased rate of infection, consistent with data
      from other ECLS centres. Antimicrobial use in ECLS patients was high relative to
      overall use in ICU patients. Larger studies are warranted to evaluate the
      diagnosis, treatment and overall approach to managing nosocomial infection in
      ECLS patients.

PMID- 22963215
TI  - Predicting energy expenditure in sepsis: Harris-Benedict and Schofield equations
      versus the Weir derivation.
AB  - BACKGROUND: Given the difficulties of using indirect calorimetry in many
      intensive care units, clinicians routinely employ predictive equations (the
      Harris-Benedict equation [HBE] and Schofield equation are commonly used) to
      estimate energy expenditure in critically ill patients. Some extrapolate CO(2)
      production (V CO(2)) and O(2) consumption (V O(2)) by the Weir derivation to
      estimate energy expenditure. These derivative methods have not been compared with
      predictive equations. OBJECTIVE: To compare prediction of energy expenditure by
      the HBE and Schofield equation with energy expenditure as estimated by the Weir
      derivation in a cohort of critically ill patients. METHODS: Between June 2009 and
      May 2010, we conducted a prospective single-centre study of 60 mechanically
      ventilated patients with sepsis of varying severity in the ICU of a metropolitan
      hospital. Three groups of patients were compared: those with systemic
      inflammatory response syndrome (SIRS), severe sepsis and septic shock. The HBE
      and Schofield equation are age-based, weight-determined, sex-specific derivations
      that may incorporate stress and/or activity factors. Total energy expenditure
      (TEE) values calculated from these equations (TEE(HBE) and TEE(SCH),
      respectively) were compared with the measured energy expenditure (MEE) calculated
      by the Weir derivation. We derived V CO(2) from end-tidal CO(2) and deduced V O2
      assuming a respiratory quotient of 0.8381. RESULTS: Mean (+/- SD) APACHE II score
      for the 60 patients was 25.7 +/- 8.4. All patients received nutrition (51
      enteral, eight parenteral and one combined) in addition to standard management
      for sepsis and multiorgan supportive therapy. Overall, 45 patients required
      inotropes and four received continuous renal replacement therapy. TEE derived
      from both predictive equations correlated well with MEE derived from the Weir
      equation (mean TEE(HBE), 7810.7 +/- 1669.2 kJ/day; mean TEE(SCH), 8029.1 +/-
      1418.6 kJ/day; mean MEE, 7660.8 +/- 2092.2 kJ/day), being within 8% of each
      other. Better correlations between TEE and MEE were observed in patients with
      APACHE II scores < 25 (vs those with scores >=25) and patients with SIRS or
      severe sepsis (vs those with septic shock). CONCLUSION: In a cohort of patients
      with sepsis, TEE values calculated by the HBE and Schofield equation matched
      reasonably well with MEE values derived from the Weir equation. Correlation was
      better in patients with less severe sepsis (SIRS and severe sepsis and APACHE II
      score < 25). Our results suggest that predictive equations have sufficient
      validity for ongoing regular use in clinical practice.

PMID- 22963216
TI  - End points for phase II trials in intensive care: recommendations from the
      Australian and New Zealand Clinical Trials Group consensus panel meeting.
AB  - BACKGROUND: There is uncertainty about which end points should be used for Phase
      II trials in critically ill patients. OBJECTIVE: To systematically evaluate
      potential end points for Phase II trials in critically ill patients. DESIGN AND
      SETTING: A report outlining a process of literature review and recommendations
      from a consensus meeting conducted on behalf of the Australian and New Zealand
      Intensive Care Society Clinical Trials Group (ANZICS CTG) in October 2011.
      RESULTS AND CONCLUSIONS: The consensus panel concluded that there are no
      adequately validated end points for Phase II trials in critically ill patients.
      However, the following were identified as potential Phase II end points: hospital
      free days to Day 90, ICU-free days to Day 28, ventilator-free days to Day 28,
      cardiovascular support-free days to Day 28, and renal replacement therapy-free
      days to Day 28. We recommend that these end points be evaluated further.

PMID- 22963217
TI  - Zebra in the intensive care unit: a metacognitive reflection on misdiagnosis.
AB  - Misdiagnosis of the cause of illness in critically ill patients is common, and a
      major cause of morbidity and mortality. We reflect upon a misdiagnosis that
      occurred in the intensive care unit of a metropolitan teaching hospital, and
      highlight the susceptibility of medical decision making to error. We examine
      recent advances in cognitive theory and how these apply to diagnosis. We discuss
      the vulnerability of such processes and - with particular reference to our case -
      why even knowledgeable and diligent clinicians are prone to misdiagnose. Finally,
      we review potential solutions, both educational and systemic, that may guard
      against the inevitable failings of the human mind, especially in a busy modern
      intensive care setting.

PMID- 22963218
TI  - Uptake and caseload of intensive care unit liaison nurse services in Australia.
AB  - BACKGROUND: Intensive care unit liaison nurses (ICULNs) represent a new clinical
      service role in the Australian health care system. These nurses aim to improve
      patient outcomes by providing a specialised support service to ward staff caring
      for acutely ill patients. As this role is relatively new, it is not known how
      many hospitals employ ICULNs or what the demand for their services is.
      OBJECTIVES: We aimed to identify the number of hospitals in the Australian
      College of Critical Care Nurses ICULN special interest group that report having
      an ICULN service, to document the timing of their introduction, and to assess
      changes in caseload since introduction. DESIGN AND SETTING: We conducted a
      retrospective observational study of the changes in ICULN operating hours and
      monthly patient reviews, and the timing of implementation of the services in
      Australian hospitals. We also assessed aspects of the ethics submission and
      approval process. RESULTS: Seventeen Australian hospitals submitted data. Before
      2004, there were only two ICULN services. The number of services dramatically
      increased between 2004 and 2007. In 14 sites, monthly patient reviews increased
      by a median of 54.3%. After adjustment for staff hours, 10 hospitals reported an
      increase in monthly patient reviews (median increase, 48.8%). Between 1999 and
      2011, the 17 services performed 123 236 patient reviews, including 73 022 ICU
      discharges (59.3%), 26 800 during or after rapid response team review (21.7%),
      and 23 414 de-novo referrals from ward staff (19.0%). CONCLUSION: The demand for
      ICULN services has increased in most hospitals since the role was adopted,
      although this varies considerably. The majority of patients are reviewed after
      ICU discharge. Further research is needed to define the scope of practice of the
      role and its impact on patient outcome, particularly in patients after ICU
      discharge.

PMID- 22963219
TI  - Crisis resource management, simulation training and the medical emergency team.
AB  - Recently there has been increased focus on improved detection and management of
      deteriorating patients in Australian hospitals. Since the introduction of the
      medical emergency team (MET) model there has been an increased role for intensive
      care unit staff in responding to deterioration of patients in hospital wards.
      Review and management of MET patients differs from the traditional model of ward
      patient review, as ICU staff may not know the patient. Furthermore, assessment
      and intervention is often time-critical and must occur simultaneously. Finally,
      about 10% of MET patients require intensive care-level interventions to be
      commenced on the ward, and this requires participation of non-ICU-trained ward
      staff. * To date, the interventions performed by MET staff and approaches to
      training responders have been relatively under investigated, particularly in the
      Australian and New Zealand context. In this article we briefly review the
      principles of the MET and contend that activation of the MET by ward staff
      represents a response to a medical crisis. We then outline why MET intervention
      differs from traditional ward-based doctor-patient encounters, and emphasise the
      importance of non-technical skills during the MET response. Finally, we suggest
      ways in which the skills required for crisis resource management within the MET
      can be taught to ICU staff, and the potential benefits, barriers and difficulties
      associated with the delivery of such training in New Zealand and Australia.

PMID- 22963220
TI  - The problem of definitions in measuring and managing ICU cognitive function.
AB  - Epidemiology and clinical trials require valid, repeatable definitions that
      ideally dichotomise patients into having, or not having, a clinical condition. *
      Some conditions are clearly dichotomous, such as pregnancy; others such as
      hypertension or obesity rely on defining a threshold on an objective scale. *
      Defining delirium and "adequate" sedation and analgesia in the intensive care
      unit is more difficult, as there is no universally agreed scale that quantifies
      the relative importance of various diagnostic features, distinguishes features
      merely observed from those actively sought, quantifies severity or fluctuation
      over time, or accounts for the variable approaches of clinicians and the effects
      of assessment environment and pharmacological treatment. Definitions of delirium
      and adequate sedation and analgesia therefore vary by assessment method and
      context, making studies using different methods and personnel not necessarily
      comparable. * Although there is no simple solution, we suggest better awareness
      of these problems will be helpful. Further, we propose a simplified
      categorisation to facilitate clinical communication and treatment in the ICU.

PMID- 22963221
TI  - Lung recruitment manoeuvres should be considered when assessing suitability for
      lung donation.

PMID- 22963222
TI  - Competencies, learning opportunities, teaching and assessments for training in
      general intensive care.

PMID- 22963223
TI  - On the origins of faster oxo exchange for uranyl(V) versus plutonyl(V).
AB  - Activation of uranyl(V) oxo bonds in the gas phase is demonstrated by reaction of
      U(16)O(2)(+) with H(2)(18)O to produce U(16)O(18)O(+) and U(18)O(2)(+). In
      contrast, neptunyl(V) and plutonyl(V) are comparatively inert toward exchange.
      Computed potential energy profiles (PEPs) reveal a lower yl oxo exchange
      transition state for uranyl(V)/water as compared with neptunyl(V)/water and
      plutonyl(V)/water. A correspondence between oxo exchange rates in gas phase and
      acid solutions is apparent; the contrasting oxo exchange rates of UO(2)(+) and
      PuO(2)(+) are considered in the context of covalent bonding in actinyls. Hydroxo
      exchange of U(16)O(2)((16)OH)(+) with H(2)(18)O to give U(16)O(2)((18)OH)(+)
      proceeded much faster than oxo exchange, in accord with a lower computed
      transition state for OH exchange. The PEP for the addition of H(2)O to UO(2)(+)
      suggests that both UO(2)(+).(H(2)O) and UO(OH)(2)(+) should be considered as
      potential products.

PMID- 22963224
TI  - Rehabilitation and return-to-sports activity after debridement and bone marrow
      stimulation of osteochondral talar defects.
AB  - An osteochondral defect (OD) is a lesion involving the articular cartilage and
      the underlying subchondral bone. ODs of the talus can severely impact on the
      quality of life of patients, who are usually young and athletic. The primary
      treatment for ODs that are too small for fixation, consists of arthroscopic
      debridement and bone marrow stimulation. This article delineates levels of
      activity, determines times for return to activity and reviews the factors that
      affect rehabilitation after arthroscopic debridement and bone marrow stimulation
      of a talar OD. Articles for review were obtained from a search of the MEDLINE
      database up to January 2012 using the search headings 'osteochondral defects',
      'bone marrow stimulation', 'sports/activity', 'rehabilitation', various other
      related factors and 'talus'. English-, Dutch- and German-language studies were
      evaluated.The review revealed that there is no consensus in the existing
      literature about rehabilitation times or return-to-sports activity times, after
      treatment with bone marrow stimulation of ODs in the talus. Furthermore, scant
      research has been conducted on these issues. The literature also showed that
      potential factors that aid rehabilitation could include youth, lower body mass
      index, smaller OD size, mobilization and treatment with growth factors, platelet
      rich plasma, biphosphonates, hyaluronic acid and pulse electromagnetic fields.
      However, most studies have been conducted in vitro or on animals. We propose a
      scheme, whereby return-to-sports activity is divided into four phases of
      increasing intensity: walking, jogging, return to non-contact sports (running
      without swerving) and return to contact sports (running with swerving and
      collision). We also recommend that research, conducted on actual sportsmen, of
      recovery times after treatment of talar ODs is warranted.

PMID- 22963226
TI  - LHD1, an allele of DTH8/Ghd8, controls late heading date in common wild rice
      (Oryza rufipogon).
AB  - Flowering at suitable time is very important for plants to adapt to complicated
      environments and produce their seeds successfully for reproduction. In rice
      (Oryza rufipogon Griff.) photoperiod regulation is one of the important factors
      for controlling heading date. Common wild rice, the ancestor of cultivated rice,
      exhibits a late heading date and a more sensitive photoperiodic response than
      cultivated rice. Here, through map-based cloning, we identified a major
      quantitative trait loci (QTL) LHD1 (Late Heading Date 1), an allele of DTH8/Ghd8,
      which controls the late heading date of wild rice and encodes a putative HAP3/NF
      YB/CBF-A subunit of the CCAAT-box-binding transcription factor. Sequence analysis
      revealed that several variants in the coding region of LHD1 were correlated with
      a late heading date, and a further complementary study successfully rescued the
      phenotype. These results suggest that a functional site for LHD1 could be among
      those variants present in the coding region. We also found that LHD1 could down
      regulate the expression of several floral transition activators such as Ehd1,
      Hd3a and RFT1 under long-day conditions, but not under short-day conditions. This
      indicates that LHD1 may delay flowering by repressing the expression of Ehd1,
      Hd3a and RFT1 under long-day conditions.

PMID- 22963227
TI  - Why technology matters as much as science in improving healthcare.
AB  - BACKGROUND: More than half a million new items of biomedical research are
      generated every year and added to Medline. How successful are we at applying this
      steady accumulation of scientific knowledge and so improving the practice of
      medicine in the USA? DISCUSSION: The conventional wisdom is that the US
      healthcare system is plagued by serious cost, access, safety and quality
      weaknesses. A comprehensive solution must involve the better translation of an
      abundance of clinical research into improved clinical practice.Yet the
      application of knowledge (i.e. technology) remains far less well funded and less
      visible than the generation, synthesis and accumulation of knowledge (i.e.
      science), and the two are only weakly integrated. Worse, technology is often seen
      merely as an adjunct to practice, e.g. electronic health records.Several key
      changes are in order. A helpful first step lies in better understanding the
      distinction between science and technology, and their complementary strengths and
      limitations. The absolute level of funding for technology development must be
      increased as well as being more integrated with traditional science-based
      clinical research. In such a mission-oriented federal funding strategy, the ties
      between basic science research and applied research would be better emphasized
      and strengthened. SUMMARY: It bears repeating that only by applying the wealth of
      existing and future scientific knowledge can healthcare delivery and patient care
      ever show significant improvement.

PMID- 22963225
TI  - Tendon regeneration in human and equine athletes: Ubi Sumus-Quo Vadimus (where
      are we and where are we going to)?
AB  - Tendon injuries are one of the most common orthopaedic problems in both human and
      equine athletes. When a damaged tendon heals naturally, it loses a substantial
      part of the original strength and elasticity. Therefore, tendons recover
      structurally (reparation) but not functionally (regeneration) after conservative
      medical or surgical treatment. Since the structure and matrix composition of
      human and equine tendons share many similarities, the nature of tendon injuries
      are also strongly comparable in both species. Therefore, the evaluation of
      regenerative therapies in horses may have applications for future human medicine
      and vice versa. The current review focuses briefly on the physiology of human and
      equine tendon in order to better comprehend the modus operandi of this structure
      under pathophysiological circumstances. In addition, the reparative effects of
      conservative medical and surgical interventions are discussed concisely, and an
      extensive overview is given on the regenerative therapies that are currently
      being explored. For the latter, the results of equine clinical studies might
      prove invaluable for gaining additional insights into the treatment of human
      tendinopathies, since not all of these novel regenerative therapies have been
      evaluated in humans yet.

PMID- 22963228
TI  - Structural model of the complete poly(A) region of HIV-1 pre-mRNA.
AB  - In the HIV-1 retrovirus, identical sequences encompassing the AAUAAA hexamer and
      the U/GU-rich downstream sequence element (DSE) that compose the core poly(A)
      site are present at both the 5' and 3' ends of the HIV-1 pre-mRNA. The AAUAAA
      hexamer is partly occluded by base pairing in the upper part of a semi-stable
      polyA hairpin. This sets the stage for regulation of HIV-1 polyadenylation, which
      involves reaction suppression at the 5' end and its stimulation at the 3' end.
      Efficient utilization of the 3' core poly(A) site is promoted by major and minor
      upstream sequence elements (USEs) which are uniquely present at the 3' end of the
      HIV-1 transcript. The structures of the HIV-1 5' and 3' poly(A) sites are defined
      by overall architecture of complete 5' and 3' untranslated terminal regions
      (UTRs). To our knowledge, there is still no structural model of a complete 3' UTR
      of the HIV-1 pre-mRNA and complete 3' poly(A) region including the USEs except
      the fact that the polyA and transactivation response (TAR) hairpins are present
      at both ends of the HIV-1 pre-mRNA. In this work, we predicted a secondary
      structure of the 3' UTR of HIV-1 pre-mRNA based on our observation that the minor
      USEs are located in a region with a high potential to form G-quadruplex
      structures. We first present structural models for the major USE, complete 3'
      poly(A) region, and almost entire 3' UTR of HIV-1 pre-mRNA. Our models are built
      based on the mfold and UNAFold secondary structure prediction of these regions
      for about 1500 HIV-1 isolates of different subtypes and recombinant forms. We
      have demonstrated that these models are valid for most of the HIV-1 isolates
      studied. The proposed models include the known TAR and polyA hairpins and new
      structural elements containing the U-rich tract of the major USE and U/GU-rich
      DSE which are fully exposed and accessible to the polyadenylation machinery,
      which confirms the functional competence of our models. 

PMID- 22963229
TI  - Perceptual effects of social salience: evidence from self-prioritization effects
      on perceptual matching.
AB  - We present novel evidence showing that new self-relevant visual associations can
      affect performance in simple shape recognition tasks. Participants associated
      labels for themselves, other people, or neutral terms with geometric shapes and
      then immediately judged whether subsequent label-shape pairings were matched.
      Across 4 experiments there was a reliable self-prioritization benefit on response
      times and perceptual sensitivity that remained across different presentation
      contexts (with self, best friend, and unfamiliar others in Experiment 1; with
      self, best friend, and neutral terms, and with self, mother, and neutral terms in
      Experiments 2A and 2B, respectively. Control studies in Experiment 3 indicated
      that the results did not reflect the length, concreteness, or familiarity of the
      words. The self-prioritization effect on shape matching also increased when
      stimuli were degraded (self shapes showing weaker effects of degradation) in
      Experiment 4A, consistent with self-information modulating perceptual processing.
      A similar effect was found when people associated different reward values to the
      shape in Experiment 4B. The results indicate that associating a stimulus to the
      self modulates its subsequent perceptual processing, and this may operate by self
      associated shapes automatically evoking the reward system.

PMID- 22963230
TI  - Keeping timbre in mind: working memory for complex sounds that can't be
      verbalized.
AB  - Properties of auditory working memory for sounds that lack strong semantic
      associations and are not readily verbalized or sung are poorly understood. We
      investigated auditory working memory capacity for lists containing 2-6 easily
      discriminable abstract sounds synthesized within a constrained timbral space, at
      delays of 1-6 s (Experiment 1), and the effect of greater perceptual variability
      among list items on capacity estimates at delays of 1-6 s (Experiment 2). Working
      memory capacity estimates of 1-2 items were found in all conditions and increased
      significantly as the perceptual variability among the list items increased.
      Nonetheless, the capacity estimates were smaller than the commonly observed
      average working memory capacity limit of 3-5 items. Decay profiles in both
      experiments were comparable with those previously reported in the verbal and
      auditory working memory literature. The results help define boundary conditions
      on capacity estimates for nonverbalizable timbres that lack strong long-term
      memory associations.

PMID- 22963231
TI  - Dissociation of S-R compatibility and Simon effects with mixed tasks and
      mappings.
AB  - Binary-choice reactions are typically faster when the stimulus location
      corresponds with that of the response than when it does not. This advantage of
      spatial correspondence is known as the stimulus-response compatibility (SRC)
      effect when the mapping of stimulus location, as the relevant stimulus dimension,
      is varied to be compatible or incompatible with response location. It is called
      the Simon effect when stimulus location is task-irrelevant. The SRC effect is
      eliminated when compatible and incompatible spatial mappings are mixed within a
      trial block, and the Simon effect is eliminated when the Simon task is mixed with
      the SRC task with incompatible spatial mapping. Eliminations of both types have
      been attributed to suppression of an automatic response-activation route. We
      tested predictions of this suppression hypothesis for conditions in which the SRC
      and Simon tasks were intermixed and the spatial mappings on the SRC trials could
      be compatible or incompatible. In Experiment 1, the two tasks were equally
      likely, as were compatible and incompatible spatial mappings on SRC trials; in
      Experiment 2, the SRC or Simon task was more frequent; and, in Experiment 3, the
      compatible or incompatible location mapping for the SRC task was more frequent.
      The SRC effect was absent overall in all experiments, whereas the Simon effect
      was robust to the manipulations and showed the characteristic decrease across the
      reaction time (RT) distribution. This dissociation of effects implies that the
      automatic response-activation route is not suppressed in mixed conditions and
      suggests that mixing influences the SRC and Simon effects by different means.

PMID- 22963234
TI  - In vivo photoacoustic therapy with cancer-targeted indocyanine green-containing
      nanoparticles.
AB  - AIM: The objective of this work was to study the photoacoustic effect of a
      special nanoparticle for selective cancer cell killing both in vitro and in vivo.
      MATERIALS & METHODS: The nanoparticles (NPs) consisting of indocyanine green
      (ICG), phospholipid-polyethylene glycol (PL-PEG) and folic acid (FA) were used as
      cancer-targeting nanoprobes. Cancer cells incubated with the ICG-PL-PEG-FA
      solution were exposed to laser pulses. Finally, tumors in mice were treated with
      photoacoustic technique. RESULTS: High selectivity of the photoacoustic
      destruction of cancer cells was observed. The tumors in mice after photoacoustic
      treatment showed a much slower growth rate. CONCLUSION: The destruction of the
      cells was due to the photoacoustic effect originating from the NPs. The ICG-PL
      PEG NP-based photoacoustic therapy would be a safe and highly efficient cancer
      treatment technique.

PMID- 22963232
TI  - The development of individuation in autism.
AB  - Evidence suggests that people with autism rely less on holistic visual
      information than typical adults. The current studies examine this by
      investigating core visual processes that contribute to holistic processing-
      namely, individuation and element grouping--and how they develop in participants
      with autism and typically developing (TD) participants matched for age, IQ, and
      gender. Individuation refers to the ability to "see" approximately four elements
      simultaneously; grouping elements can modify how many elements can be
      individuated. We examined these processes using two well-established paradigms,
      rapid enumeration and multiple object tracking (MOT). In both tasks, a
      performance limit of four elements in typical adults is thought to reflect
      individuation capacity. Participants with autism displayed a smaller
      individuation capacity than TD controls, regardless of whether they were
      enumerating static elements or tracking moving ones. To manipulate the holistic
      information available via element grouping, elements were arranged into a design
      in rapid enumeration, or moved together in MOT. Performance in participants with
      autism was affected to a similar degree as TD participants by element grouping,
      whether the manipulation helped or hurt performance, consistent with evidence
      that some types of gestalt/grouping information are processed typically in
      autism. There was substantial development from childhood to adolescence in the
      speed of individuation in those with autism, but not from adolescence to
      adulthood, a pattern distinct from TD participants. These results reveal how core
      visual processes function in autism, and provide insight into the architecture of
      vision (i.e., individuation appears distinct from visual strengths in autism,
      such as visual search).

PMID- 22963233
TI  - U.K. consensus statement on safe clinical prescribing of bexarotene for patients
      with cutaneous T-cell lymphoma.
AB  - BACKGROUND: Bexarotene is a synthetic retinoid from the subclass of retinoids
      called rexinoids which selectively activate retinoid X receptors. It has activity
      in cutaneous T-cell lymphoma (CTCL) and has been approved by the European
      Medicines Agency since 1999 for treatment of the skin manifestations of advanced
      stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic
      treatment. In vivo bexarotene produces primary hypothyroidism which may be
      managed with thyroxine replacement. It also affects lipid metabolism, typically
      resulting in raised triglycerides, which requires prophylactic lipid-modification
      therapy. Effects on neutrophils, glucose and liver function may also occur. These
      side-effects are dose dependent and may be controlled with corrective therapy or
      dose adjustments. OBJECTIVES:   To produce a U.K. statement outlining a
      bexarotene dosing schedule and monitoring protocol to enable bexarotene
      prescribers to deliver bexarotene safely for optimal effect. METHODS:  Leaders
      from U.K. supraregional centres produced this consensus statement after a series
      of meetings and a review of the literature. RESULTS:  The statement outlines a
      bexarotene dosing schedule and monitoring protocol. This gives instructions on
      monitoring and treating thyroid, lipid, liver, blood count, creatine kinase,
      glucose and amylase abnormalities. The statement also includes algorithms for a
      bexarotene protocol and lipid management, which may be used in the clinical
      setting. CONCLUSION:  Clinical prescribing of bexarotene for patients with CTCL
      requires careful monitoring to allow safe administration of bexarotene at the
      optimal dose.

PMID- 22963235
TI  - Patient self-efficacy and spouse perception of spousal support are associated
      with lower patient weight: baseline results from a spousal support behavioral
      intervention.
AB  - Obesity and related chronic illnesses are leading causes of death and excessive
      health care costs, necessitating identification of factors that can help patients
      achieve and maintain healthy weight. Greater self-efficacy and perceived spousal
      support in patients have been associated with successful weight management. The
      current study also assesses self-efficacy and perceived support in spouses and
      whether these factors are related to patient weight. At baseline of a spousal
      support trial, patients and spouses (N = 255 couples) each completed measures of
      self-efficacy and spousal support for their own exercise and healthy eating
      behaviors. We fit a multivariable regression model to examine the relationship
      between these factors and patient weight. Patients were 95% males and 65% Whites,
      with average age of 61 years (SD = 12) and weight of 212 lbs (SD = 42). Spouses
      were 64% Whites, with average age of 59 years (SD = 12). Factors associated with
      lower patient weight were older patient age (estimate = -0.8 lbs, p < .01),
      normal blood pressure (estimate = -17.6 lbs, p < .01), higher patient self
      efficacy for eating healthy (estimate = -3.8 lbs, p = .02), and spouse greater
      perceived support for eating healthy (estimate = -10.0 lbs, p = .03). Future
      research should explore the causal pathways between perceived support and health
      outcomes to establish whether patient support behaviors could be a point of
      intervention for weight management.

PMID- 22963236
TI  - The importance of early referral for the treatment of chronic kidney disease: a
      Danish nationwide cohort study.
AB  - BACKGROUND: Many patients with advanced chronic kidney disease are referred late
      to renal units. This is associated with negative aspects. The purpose of the
      present study was to characterize late versus early referrals for renal
      replacement therapy including their renal disease, health care contacts and
      medical treatment before renal replacement therapy (RRT) and the consequences for
      RRT modality and mortality. METHODS: Nationwide cohort study including 4495 RRT
      patients identified in the Danish Nephrology Registry 1999-2006. The cohort was
      followed to end 2007 by linkage to other national registries. Late referral:
      follow-up <=16 weeks in renal unit before RRT start. Cox proportional hazards
      models were used to estimate the relative risk of mortality or waiting list
      status within 365 days in late referrals versus early referrals. RESULTS: A total
      of 1727 (38%) incident RRT patients were referred late. Among these, 72% were
      treated in non-nephrology hospital departments and 91% in general practice 2
      years to 16 weeks before RRT start. Fewer late referrals received recommended pre
      RRT treatment as judged by renin-angiotensin-system blockade: 32% versus 57% or
      the D-vitamin analogue alfacalcidol: 5% versus 30% (P < .001). Primary RRT
      modality was peritoneal dialysis: 18% in late versus 32% in early referrals (P <
      .001), 7% versus 30%, respectively, had an arteriovenous dialysis-fistula (P <
      .001) and 0.2% versus 6% were on the waiting-list for renal transplantation (P <
      .001) before RRT start. One-year-mortality was higher in late referrals: hazard
      ratio 1.55 (CI 95% 1.35-1.78). In a subgroup, 30% (CI 95% 25-35%) late and 9% (CI
      95% 6-12%) early referrals had plasma creatinine <=150% of upper reference limit
      within 1 to 2 years before RRT start (P < .001). CONCLUSIONS: Late nephrology
      referrals were well-known to the healthcare system before referral for RRT start
      and more often had near normal plasma creatinine levels within 2 years before RRT
      start. They infrequently received available treatment or optimal first RRT
      modality. An increased effort to identify these patients in the healthcare system
      in time for proper pre-dialysis care including preparation for RRT is needed.

PMID- 22963238
TI  - ISIAQ and the Academy of Fellows.

PMID- 22963237
TI  - Light-inducible spatiotemporal control of gene activation by customizable zinc
      finger transcription factors.
AB  - Advanced gene regulatory systems are necessary for scientific research, synthetic
      biology, and gene-based medicine. An ideal system would allow facile
      spatiotemporal manipulation of gene expression within a cell population that is
      tunable, reversible, repeatable, and can be targeted to diverse DNA sequences. To
      meet these criteria, a gene regulation system was engineered that combines light
      sensitive proteins and programmable zinc finger transcription factors. This
      system, light-inducible transcription using engineered zinc finger proteins
      (LITEZ), uses two light-inducible dimerizing proteins from Arabidopsis thaliana,
      GIGANTEA and the LOV domain of FKF1, to control synthetic zinc finger
      transcription factor activity in human cells. Activation of gene expression in
      human cells engineered with LITEZ was reversible and repeatable by modulating the
      duration of illumination. The level of gene expression could also be controlled
      by modulating light intensity. Finally, gene expression could be activated in a
      spatially defined pattern by illuminating the human cell culture through a
      photomask of arbitrary geometry. LITEZ enables new approaches for precisely
      regulating gene expression in biotechnology and medicine, as well as studying
      gene function, cell-cell interactions, and tissue morphogenesis.

PMID- 22963239
TI  - Transforming growth factor beta induces sensory neuronal hyperexcitability, and
      contributes to pancreatic pain and hyperalgesia in rats with chronic
      pancreatitis.
AB  - BACKGROUND: Transforming growth factor beta (TGFbeta) is upregulated in chronic
      inflammation, where it plays a key role in wound healing and promoting fibrosis.
      However, little is known about the peripheral effects of TGFbeta on nociception.
      METHODS: We tested the in vitro effects of TGFbeta1 on the excitability of dorsal
      root ganglia (DRG) neurons and the function of potassium (K) channels. We also
      studied the effects of TGFbeta1 infusion on pain responses to noxious electrical
      stimulation in healthy rats as well as the effects of neutralization of TGFbeta1
      on evoked pain behaviors in a rat model of chronic pancreatitis. RESULTS:
      Exposure to TGFbeta1 in vitro increased sensory neuronal excitability, decreased
      voltage-gated A-type K(+) currents (IA) and downregulated expression of the Kv1.4
      (KCNA4) gene. Further TGFbeta1 infusion into the naive rat pancreas in vivo
      induces hyperalgesia and conversely, neutralization of TGFbeta1 attenuates
      hyperalgesia only in rats with experimental chronic pancreatitis. Paradoxically,
      TGFbeta1 neutralization in naive rats results in pancreatic hyperalgesia.
      CONCLUSIONS: TGFbeta1 is an important and complex modulator of sensory neuronal
      function in chronic inflammation, providing a link between fibrosis and
      nociception and is a potentially novel target for the treatment of persistent
      pain associated with chronic pancreatitis.

PMID- 22963240
TI  - De novo engineering of a human cystathionine-gamma-lyase for systemic (L)
      Methionine depletion cancer therapy.
AB  - It has been known for nearly a half century that human tumors, including those
      derived from the nervous system such as glioblastomas, medulloblastoma, and
      neuroblastomas are much more sensitive than normal tissues to l-methionine (l
      Met) starvation. More recently, systemic l-Met depletion by administration of
      Pseudomonas putida methionine-gamma-lyase (MGL) could effectively inhibit human
      tumors xenografted in mice. However, bacterial-derived MGLs are unstable in serum
      (t(1/2) = 1.9 +/- 0.2 h) and highly immunogenic in primates. Since the human
      genome does not encode a human MGL enzyme, we created de novo a methionine
      degrading enzyme by reengineering the structurally homologous pyridoxal phosphate
      dependent human enzyme cystathionine-gamma-lyase (hCGL). hCGL degrades l
      cystathionine but displays no promiscuous activity toward l-Met. Rational design
      and scanning saturation mutagenesis led to the generation of a variant containing
      three amino acid substitutions (hCGL-NLV) that degraded l-Met with a k(cat)/K(M)
      of 5.6 * 10(2) M(-1) s(-1) and displayed a serum deactivation t(1/2) = 78 +/- 5 h
      (non-PEGylated). In vitro, the cytotoxicity of hCGL-NLV toward 14 neuroblastoma
      cell lines was essentially indistinguishable from that of the P. putida MGL.
      Intravenous administration of PEGylated hCGL-NLV in mice reduced serum l-Met from
      123 MUM to <5 MUM for over 30 h. Importantly, treatment of neuroblastoma mouse
      xenografts with PEGylated hCGL-NLV resulted in near complete cessation of tumor
      growth. Since the mode of action of hCGL-NLV does not require breaching the blood
      brain barrier, this enzyme may have potential application for sensitive tumors
      that arise from or metastasize to the central nervous system.

PMID- 22963246
TI  - Biodegradation of high-molecular-weight polycyclic aromatic hydrocarbons by a
      wood-degrading consortium at low temperatures.
AB  - This study evaluates the ability of two bacterial consortia (C2PL05 and BOS08),
      extracted from very different environments, to degrade low- (naphthalene,
      phenanthrene, anthracene) and high- (pyrene, perylene) molecular-weight
      polycyclic aromatic hydrocarbons (PAHs) at high (15-25  degrees C) and low (5-15 
      degrees C) temperature ranges. C2PL05 was isolated from a soil in an area
      chronically and heavily contaminated with petroleum hydrocarbons and BOS08 from
      decomposing wood in an unpolluted forest, free of PAHs. Bacterial consortia were
      described by cultivable and noncultivable techniques (denaturing gradient gel
      electrophoresis). Fungal DNA was not observed within the wood-decomposing
      consortium and fungal activity was therefore negligible during most of the PAH
      degradation process. PAH-degrading bacterial populations, measured by most
      probable number enumeration, increased during the exponential phase. Toxicity
      estimated by the Microtox method was reduced to low levels and final PAH
      depletion, determined by HPLC, confirmed the high degree (54% and 99%,
      respectively) of low- and high-molecular-weight PAH degradation capacity of the
      two consortia. PAH-degrading capacity was also confirmed at low temperatures, and
      especially by consortium BOS08 not previously exposed to those toxic compounds,
      where strains of Acinetobacter sp., Pseudomonas sp., Ralstonia sp. and
      Microbacterium sp. were identified.

PMID- 22963247
TI  - Immediate newborn outcome and mode of delivery: use of standardized fetal heart
      rate pattern management.
AB  - OBJECTIVE: To determine whether a rule-based system for fetal heart rate
      interpretation can result in reduced metabolic acidemia without increasing
      obstetrical intervention. METHODS: Rates of vacuum-assisted delivery and Cesarean
      sections, and umbilical artery pH and base excess values were determined over a 5
      year period in a single hospital with 3907 deliveries in Japan. Results were
      compared for 2 years before and 2 years after a 6-month training period in rule
      based fetal heart rate interpretation. RESULTS: The pre- and post-training rates
      of unscheduled Cesarean deliveries (4.8% vs. 6.0%) and vacuum deliveries (21.2%
      vs. 18.1%) did not differ significantly. The rates of umbilical arterial pH <7.15
      (1.51% vs. 0.18%, p < 0.05) and base excess <-12 mEq/L (1.76% vs. 0.25%, p <
      0.05) were significantly lower after training. CONCLUSION: A standardized fetal
      heart rate pattern management system was associated with a 7-fold reduction of
      newborn metabolic acidemia with no change in operative intervention.

PMID- 22963248
TI  - Differences in ovarian aging patterns between races are associated with ovarian
      genotypes and sub-genotypes of the FMR1 gene.
AB  - BACKGROUND: Ovarian aging patterns differ between races, and appear to affect
      fertility treatment outcomes. What causes these differences is, however, unknown.
      Variations in ovarian aging patterns have recently been associated with specific
      ovarian genotypes and sub-genotypes of the FMR1 gene. We, therefore, attempted to
      determine differences in how functional ovarian reserve (FOR) changes with
      advancing age between races, and whether changes are associated with differences
      in distribution of ovarian genotypes and sub-genotypes of the FMR1 gene. METHODS:
      We determined in association with in vitro fertilization (IVF) FOR in 62 young
      Caucasian, African and Asian oocyte donors and 536 older infertility patients of
      all three races, based on follicle stimulating hormone (FSH), anti-Mullerian
      hormone (AMH) and oocyte yields, and investigated whether differences between
      races are associated with differences in distribution of FMR1 genotypes and sub
      genotypes. RESULTS: Changes in distribution of mean FSH, AMH and oocyte yields
      between young donors and older infertility patients were significant (all P <
      0.001). Donors did not demonstrate significant differences between races in AMH
      and FSH but demonstrated significant differences in oocyte yields [F(2,59) =
      4.22, P = 0.019]: Specifically, African donors demonstrated larger oocyte yields
      than Caucasians (P = 0.008) and Asians (P = 0.022). In patients, AMH levels
      differed significantly between races [F (2,533) = 4.25, P = 0.015]. Holm-Sidak
      post-hoc comparisons demonstrated that Caucasians demonstrated lower AMH in
      comparison to Asians (P = 0.007). Percentages of FMR1 genotypes and sub-genotypes
      in patients varied significantly between races, with Asians demonstrating fewer
      het-norm/low sub-genotypes than Caucasians and Africans (P = 0.012). CONCLUSION:
      FOR changes in different races at different rates, and appears to parallel
      ovarian FMR1 genotypes and sub-genotype distributions. Differences in ovarian
      aging between races may, therefore, be FMR1-associated.

PMID- 22963249
TI  - Experimental and time-dependent density functional theory characterization of the
      UV-visible spectra of monomeric and MU-oxo dimeric ferriprotoporphyrin IX.
AB  - Speciation of ferriprotoporphyrin IX, Fe(III)PPIX, in aqueous solution is
      complex. Despite the use of its characteristic spectroscopic features for
      identification, the theoretical basis of the unique UV-visible absorbance
      spectrum of MU-[Fe(III)PPIX](2)O has not been explored. To investigate this and
      to establish a structural and spectroscopic model for Fe(III)PPIX species,
      density functional theory (DFT) calculations were undertaken for H(2)O
      Fe(III)PPIX and MU-[Fe(III)PPIX](2)O. The models agreed with related
      Fe(III)porphyrin crystal structures and reproduced vibrational spectra well. The
      UV-visible absorbance spectra of H(2)O-Fe(III)PPIX and MU-[Fe(III)PPIX](2)O were
      calculated using time-dependent DFT and reproduced major features of the
      experimental spectra of both. Transitions contributing to calculated excitations
      have been identified. The features of the electronic spectrum calculated for MU
      [Fe(III)PPIX](2)O were attributed to delocalization of electron density between
      the two porphyrin rings of the dimer, the weaker ligand field of the axial
      ligand, and antiferromagnetic coupling of the Fe(III) centers. Room temperature
      magnetic circular dichroism (MCD) spectra have been recorded and are shown to be
      useful in distinguishing between these two Fe(III)PPIX species. Bands underlying
      major spectroscopic features were identified through simultaneous deconvolution
      of UV-visible and MCD spectra. Computed UV-visible spectra were compared to
      deconvoluted spectra. Interpretation of the prominent bands of H(2)O-Fe(III)PPIX
      largely conforms to previous literature. Owing to the weak paramagnetism of MU
      [Fe(III)PPIX](2)O at room temperature and the larger number of underlying
      excitations, interpretation of its experimental UV-visible spectrum was
      necessarily tentative. Nonetheless, comparison with the calculated spectra of
      antiferromagnetically coupled and paramagnetic forms of the MU-oxo dimer of
      Fe(III)porphine suggested that the composition of the Soret band involves a
      mixture of pi->pi* and pi->d(pi) charge transfer transitions. The Q-band and
      charge transfer bands appear to amalgamate into a mixed low energy envelope
      consisting of excitations with heavily admixed pi->pi* and charge transfer
      transitions.

PMID- 22963250
TI  - Microbial water quality risks to public health: potable water assessment for a
      flood-affected town in northern Pakistan.
AB  - INTRODUCTION: In mid-July 2010 flash flooding in Pakistan destroyed the basic
      water, environmental sanitation and livelihood infrastructures in 82 districts.
      Two months later, the local press of Swat (northern Pakistan) reported that
      several residents of Marghazar town became ill and were hospitalized after
      drinking contaminated water. A non-governmental organization (Oxfam GB) team took
      action to determine the causes of this incident and analyzed the community
      drinking water supply. METHODS: Standard methods were used to analyze six physio
      chemical and four microbiological water quality parameters at five selected
      sampling locations in the water supply system. RESULTS: The samples from sites
      numbers (SN)02, 03, 04 and 05 were found to be microbiologically unfit for
      drinking due to the presence of Escherichia coli, Shigella, Salmonella and
      Staphylococcus aureus (range 18-96 +/- 14 cfu/100 mL). However, the pH,
      conductivity, total dissolved solid, total hardness as calcium carbonate and
      nitrate as NO3(-2) of all the samples were within WHO permissible limits. Higher
      turbidities were recorded at SN04 and 05 of 6 +/- 0.23 and 9 +/- 1.23,
      respectively. CONCLUSION: Quantitative results revealed the presence of
      pathogenic organisms and water quality risk factors due to the damaged water and
      environmental sanitation infrastructure. Continued water quality monitoring, the
      application of household based disinfectants, and healthy domestic hygiene
      practices are highly recommended in similar circumstances.

PMID- 22963251
TI  - Regulation of brassinosteroid biosynthesis and inactivation.
AB  - Brassinosteroids (BRs) are a group of naturally-occurring steroidal phytohormones
      playing fundamental roles during normal plant growth and development. Using a
      combination of experimental approaches, including analytical chemistry, genetics,
      and biochemistry, the major BR biosynthetic pathway has been largely elucidated.
      The least-understood knowledge in the BR research field is probably the molecular
      mechanisms controlling the bioactive levels of BRs in response to various
      developmental and environmental cues. In this review, we focus our discussion on
      a recently-proposed, 8-step predominant BR biosynthetic pathway, several newly
      identified transcription factors regulating the expression of key enzymes that
      catalyze BR biosynthesis, and up-to-date information about the mechanisms that
      plants use to inactivate unnecessary BRs.

PMID- 22963252
TI  - Comparative physiological and proteomic response to abrupt low temperature stress
      between two winter wheat cultivars differing in low temperature tolerance.
AB  - Abrupt temperature reduction in winter wheat at either autumn seedling stage
      prior to vernalisation or early spring crown stage can cause severe crop damage
      and reduce production. Many studies have reported the physiological and molecular
      mechanisms underlying cold acclimation in winter wheat by comparing it with
      spring wheat. However, processes associated with abrupt temperature reduction in
      autumn seedling stage prior to vernalisation in winter wheat are less understood.
      In this study, physiological and molecular responses of winter wheat seedlings to
      abrupt low temperature (LT) stress were characterised in the relatively LT
      tolerant winter wheat cultivar Shixin 828 by comparing it with the relatively LT
      sensitive cultivar Shiluan 02-1 using a combination of physiological, proteomics
      and biochemical approaches. Shixin 828 was tolerant to abrupt LT stress, while
      Shiluan 02-1 exhibited high levels of reactive oxygen species (ROS) and leaf cell
      death. Significant increases in relative abundance of antioxidant-related
      proteins were found in Shixin 828 leaves, which correlate with observed higher
      antioxidant enzyme activity in Shixin 828 compared to Shiluan 02-1. Proteomics
      analysis also indicated that carbohydrate metabolism-related proteins were more
      abundant in Shiluan 02-1, correlating with observed accumulation of soluble
      sugars in Shiluan 02-1 leaves. Amino acid analysis revealed a strong response to
      LT stress in wheat leaves. A negative effect of exogenous sucrose on LT tolerance
      was also found. This study indicates that high ROS scavenging capacity and high
      abundance of photosynthesis-related proteins might play a role in winter wheat
      response to abrupt LT stress. In contrast, excess accumulation of soluble sugars
      might be disadvantageous for LT tolerance in the wheat cultivar Shiluan 02-1.

PMID- 22963254
TI  - Viral meningitis, active and reserve components, U.S. Armed Forces,  2002-2011.
AB  - Viruses are the most common causes of meningitis, a condition characterized by
      inflammation of the protective membranes that surround the brain and spinal cord.
      During the 10-year surveillance period, there were 3,205 confirmed cases, 724
      probable cases, and 2,495 suspected cases of viral meningitis among active and
      reserve component members. In all three categories of cases, the most common
      diagnoses were meningitis due to  enteroviruses; however a majority of these were
      unspecified enteroviruses.  Nearly two-thirds (64.2%) of all cases due to
      enteroviral infection were hospitalized; on average, cases were hospitalized for
      3.2 days. Numbers of cases peaked in late summer/early fall; and higher than
      average numbers of cases in 2003 reflected several outbreaks that occurred in
      civilian populations that year. Six states (Texas, California, Virginia, North
      Carolina, Florida, Georgia) reported the most cases in 2003 and overall during
      the period. Prevention of viral meningitis relies upon the interruption of viral
      transmission, e.g., thorough hand washing and disinfection of contaminated
      surfaces.

PMID- 22963253
TI  - Pediatric case report: clinical profile of a patient with PCWH with p.Q377X
      nonsense mutation in the SOX10 gene.
AB  - We report the case of a Japanese patient with PCWH, a neurological variant of
      Waardenburg type 4. Direct sequencing of the genomic DNA obtained from peripheral
      leukocytes revealed the p.Q377X nonsense mutation in the SOX10 gene. The patient
      had mottled hypopigmented macules on the trunk since birth; such macules have not
      been described previously. The so-called "white forelock", a triangular or
      diamond shaped leukoderma on the forehead, was absent. We also reviewed and
      summarized the outcomes of 23 patients with Waardenburg syndrome type 4, PCWH and
      Yemenite deaf-blind hypopigmentation syndrome, in which SOX10 mutations were
      identified. Among them, 17 cases were reported to have hypopigmented skin
      macule(s). The five patients who had the white forelock had PCWH with severe
      neurological complications. Paradoxically, two cases had hyperpigmented spots.
      Heterochromia of the iris was reported in four patients.

PMID- 22963241
TI  - Metagenomic analysis reveals a functional signature for biomass degradation by
      cecal microbiota in the leaf-eating flying squirrel (Petaurista alborufus lena).
AB  - BACKGROUND: Animals co-evolve with their gut microbiota; the latter can perform
      complex metabolic reactions that cannot be done independently by the host.
      Although the importance of gut microbiota has been well demonstrated, there is a
      paucity of research regarding its role in foliage-foraging mammals with a
      specialized digestive system. RESULTS: In this study, a 16S rRNA gene survey and
      metagenomic sequencing were used to characterize genetic diversity and functional
      capability of cecal microbiota of the folivorous flying squirrel (Petaurista
      alborufus lena). Phylogenetic compositions of the cecal microbiota derived from 3
      flying squirrels were dominated by Firmicutes. Based on end-sequences of fosmid
      clones from 1 flying squirrel, we inferred that microbial metabolism greatly
      contributed to intestinal functions, including degradation of carbohydrates,
      metabolism of proteins, and synthesis of vitamins. Moreover, 33 polysaccharide
      degrading enzymes and 2 large genomic fragments containing a series of
      carbohydrate-associated genes were identified. CONCLUSIONS: Cecal microbiota of
      the leaf-eating flying squirrel have great metabolic potential for converting
      diverse plant materials into absorbable nutrients. The present study should serve
      as the basis for future investigations, using metagenomic approaches to elucidate
      the intricate mechanisms and interactions between host and gut microbiota of the
      flying squirrel digestive system, as well as other mammals with similar
      adaptations.

PMID- 22963255
TI  - Updates: Routine screening for antibodies to human immunodeficiency virus, type 1
      (HIV-1), civilian applicants for U.S. military service and U.S. Armed Forces,
      active and reserve components.
AB  - During routine testing of civilian applicants for U.S. military service, the
      overall seroprevalence of antibodies to HIV-1 in 2011 was the second lowest of
      any year since 1990. Among members of the active components of the U.S. Army, 
      HIV-1 seroprevalences were higher during 2008 to 2011 than in recent prior years.
      Among members of the active components of the U.S. Air Force, Navy and Marine
      Corps, the Marine Corps Reserve, and the Army National Guard,  HIV-1
      seroprevalences have slightly declined or remained relatively stable for at least
      ten years. In the reserve components of most service branches, it is difficult to
      discern long-term trends because of instability of seroprevalences in the
      relatively small numbers of reserve component members tested each year.
      Monitoring of HIV-1 seroprevalences can help target and focus prevention
      initiatives.  The recent repeal of the Don't Ask Don't Tell policy has created
      opportunities for prevention messages targeted to men who have sex with men.

PMID- 22963256
TI  - Pertussis diagnoses among service members and other beneficiaries of  the U.S.
      Military Health System, January 2005-June 2012.
AB  - Pertussis ("whooping cough") is a highly infectious respiratory disease caused by
      the bacterium Bordetella pertussis. Individuals at highest risk are infants and
      unvaccinated children; however, there have been recent increases in incidence
      among adolescent and young adult populations in the United States.  During the
      surveillance period, there were 476 confirmed and 3,073 probable cases of
      pertussis among U.S. military members and other beneficiaries of the U.S.
      Military Health System. Among service members there were 77 and  13 confirmed
      cases in active and reserve component members, respectively.  In comparison,
      infants and children aged 15 years and younger accounted for over half of all
      confirmed cases (n=244). Several spatiotemporal clusters of pertussis among
      military healthcare beneficiaries were associated with outbreaks in adjacent non
      military communities, particularly in five states  (California, Texas, Florida,
      Washington, and New York); one cluster occurred in a military community in
      Okinawa, Japan.

PMID- 22963257
TI  - Hospitalizations for hepatitis A, B, and C, active component, U.S. Armed Forces,
      1991-2011.

PMID- 22963258
TI  - Current challenges in the discovery of novel antibacterials from microbial
      natural products.
AB  - Microbial natural products have been for decades one of the most successful
      sources of drugs to treat infectious diseases. The high occurrence of resistances
      to all major classes of known antibiotics represents today a new challenge and
      new classes of antibacterial compounds are urgently needed to respond to this
      unmet clinical need. While natural products discovery programs have been
      gradually abandoned by big pharma, smaller biotechnology companies and other
      research organizations are taking the lead in the discovery of novel
      antibacterials. A survey of recent patents has shown that in spite of the
      efforts, few novel compounds are being developed that can overcome most of the
      emerging multi-resistant and pan-resistant pathogens. In order to respond to the
      current challenges of discovering novel antibiotics, new approaches are required
      to be developed to further exploit the microbial resources and their biosynthetic
      potential as an untapped source of novel metabolites. Strategies to mine
      microbial collections for orphan biosynthetic pathways and novel species thought
      to be uncultivable, are emerging as a need within antibacterial drug discovery
      programs, in combination with high throughput screening and chemical
      dereplication of novel compounds. Different innovative methods that are being
      developed to respond to the new challenges that are faced today by drug discovery
      programs will ensure the evolution of these strategies into a completely new
      framework that will address the renovated interest in the discovery of novel
      classes of antibiotics.

PMID- 22963259
TI  - Amenable mortality as a performance indicator of Italian health-care services.
AB  - BACKGROUND: Mortality amenable to health-care services ('amenable mortality') has
      been defined as "premature deaths that should not occur in the presence of timely
      and effective health care" and as "conditions for which effective clinical
      interventions exist." We analyzed the regional variability in health-care
      services using amenable mortality as a performance indicator. Convergent validity
      was examined against other indicators, such as health expenditure, GDP per
      capita, life expectancy at birth, disability-free life expectancy at age 15,
      number of diagnostic and laboratory tests per 1,000 inhabitants, and the
      prevalence of cancer and cardiovascular diseases. METHODS: Amenable mortality
      rate was calculated as the average annual number of deaths in the population aged
      0-74 years per 100,000 inhabitants, and it was then stratified by gender and
      region. Data were drawn from national mortality statistics for the period 2006
      08. RESULTS: During the study period (2006-08), the age-standardized death rate
      (SDR) amenable to health-care services in Italy was 62.6 per 100,000 inhabitants:
      66.0 per 100,000 for males and 59.1 per 100,000 for females. Significant regional
      variations ranged from 54.1 per 100,000 inhabitants in Alto Adige to 76.3 per
      100,000 in Campania. Regional variability in SDR was examined separately for male
      and females. The variability proved to be statistically significant for both
      males and females (males: Q-test = 638.5, p < 0.001; females: Q-test = 700.1, p <
      0.001). However, among men, we found a clear-cut divide in SDR values between
      Central and Southern Italy; among women, this divide was less pronounced.
      Amenable mortality was negatively correlated with life expectancy at birth for
      both genders (male: r = -0.64, p = 0.002; female: r = -0.88, p <0.001) and with
      disability-free life expectancy at age 15 (male: r = -0.70, p <0.001; female: r =
      -0.67, p <0.001). Amenable mortality displayed a statistically significant
      negative relationship with GDP per capita, the quantity of diagnostic and
      laboratory tests per 1,000 inhabitants, and the prevalence of cancer.
      CONCLUSIONS: Amenable mortality shows a wide variation across Italian regions and
      an inverse relationship with life expectancy and GDP per capita, as expected.

PMID- 22963260
TI  - Increasing extracellular matrix collagen level and MMP activity induces cyst
      development in polycystic kidney disease.
AB  - BACKGROUND: Polycystic Kidney Disease (PKD) kidneys exhibit increased
      extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs)
      activity. We investigated the role of these increases on cystic disease
      progression in PKD kidneys. METHODS: We examined the role of type I collagen
      (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using
      both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model
      of PKD. RESULTS: We found that collagen concentration is critical in controlling
      the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D
      structures at collagen I concentrations lower than 1 mg/ml but began forming
      tubules when the concentration reaches 1 mg/ml. Significantly, these cells began
      to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios
      of cyst to tubule structures increased as the collagen I concentration increased.
      These cells exclusively formed cyst structures at a collagen I concentration of
      1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly
      induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs
      activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed
      cyst growth. More importantly, the treatment of PCK rats with doxycycline
      significantly decreased renal tubule cell proliferation and markedly inhibited
      the cystic disease progression. CONCLUSIONS: Our data suggest that increased
      collagen expression and MMP activity in PKD kidneys may induce cyst formation and
      expansion. Our findings also suggest that MMPs may serve as a therapeutic target
      for the treatment of human PKD.

PMID- 22963261
TI  - Duplicated laboratory tests: evaluation of a computerized alert intervention
      abstract.
AB  - Redundant testing contributes to reductions in healthcare system efficiency. The
      purpose of this study was to: (1) determine if the use of a computerized alert
      would reduce the number and cost of duplicated Acute Hepatitis Profile (AHP)
      laboratory tests and (2) assess what patient, test, and system factors were
      associated with duplication. This study used a quasi-experimental pre- and post
      test design to determine the proportion of duplication of the AHP test before and
      after implementation of a computerized alert intervention. The AHP test was
      duplicated if the test was requested again within 15 days of the initial test
      being performed and the result present in the medical record. The intervention
      consisted of a computerized alert (pop-up window) that indicated to the clinician
      that the test had recently been ordered. A total of 674 AHP tests were performed
      in the pre-intervention period and 692 in the postintervention group. In the pre
      intervention period, 53 (7.9%) were duplicated and in postintervention, 18 (2.6%)
      were duplicated (p<.001). The implementation of the alert was shown to
      significantly reduce associated costs of duplicated AHP tests (p<=.001).
      Implementation of computerized alerts may be useful in reducing duplicate
      laboratory tests and improving healthcare system efficiency.

PMID- 22963262
TI  - Diastereoisomer- and enantiomer-specific accumulation, depuration, and
      bioisomerization of hexabromocyclododecanes in zebrafish (Danio rerio).
AB  - In this study, zebrafish (Danio rerio) were exposed to two dietary concentrations
      of individual HBCD diastereoisomers (alpha-, beta-, and gamma-HBCD) for 42 days,
      followed by clean food for 21 days, to examine bioaccumulation, depuration, and
      enantiomer fractions (EFs) of HBCD diastereoisomers and to test the
      bioisomerization of HBCDs in fish. The depuration of alpha-, beta-, and gamma
      HBCD in zebrafish followed the first-order process. Bioaccumulation parameters of
      the three diastereoisomers differed between low and high dose, suggesting that
      the bioaccumulation of them is concentration dependent. Calculated assimilation
      efficiencies (AEs), biomagnification factors (BMFs), and half-lives (t(1/2)) of
      alpha-HBCD were the highest among the three diastereoisomers. Furthermore, the
      study showed that zebrafish could biotransform gamma-HBCD to alpha-HBCD. The
      highest AE, BMF, and t(1/2) of alpha-HBCD and bioisomerization of gamma-HBCD to
      alpha-HBCD could explain why alpha-HBCD appears to be dominant in biota samples.
      The EFs for alpha- and gamma-HBCD in zebrafish estimated at different times of
      bioaccumulation and depuration were all significantly greater than those in
      corresponding food (P < 0.05), indicating selective enrichment of (+) alpha
      enantiomer and (+) gamma-enantiomer relative to (-) alpha-enantiomer and (-)
      gamma-enantiomer, respectively.

PMID- 22963263
TI  - Activity-based protein profiling of the Escherichia coli GlpG rhomboid protein
      delineates the catalytic core.
AB  - Rhomboid proteins comprise the largest class of intramembrane protease known,
      being conserved from bacteria to humans. The functional status of these proteases
      is typically assessed through direct or indirect detection of peptide cleavage
      products. Although these assays can report on the ability of a rhomboid to
      catalyze peptide bond cleavage, differences in measured hydrolysis rates can
      reflect changes in the structure and activity of catalytic residues, as well as
      the ability of the substrate to access the active site. Here we show that a
      highly reactive and sterically unencumbered fluorophosphonate activity-based
      protein profiling probe can be used to report on the catalytic integrity of
      active site residues in the Escherichia coli GlpG protein. We used results
      obtained with this probe on GlpG in proteomic samples, in combination with a
      conventional assay of proteolytic function on purified samples, to identify
      residues that are located on the cytoplasmic side of the lipid bilayer that are
      required for maximal proteolytic activity. Regions tested include the 90-residue
      aqueous-exposed N-terminus that encompasses a globular structure that we have
      determined by solution nuclear magnetic resonance, along with residues on the
      cytoplasmic side of the transmembrane domain core. While in most cases mutation
      or elimination of these residues did not significantly alter the catalytic status
      of the GlpG active site, the lipid-facing residue Arg227 was found to be
      important for maintaining a catalytically competent active site. In addition, we
      found a functionally critical region outside the transmembrane domain (TMD) core
      that is required for maximal protease activity. This region encompasses an
      additional 8-10 residues on the N-terminal side of the TMD core that precedes the
      first transmembrane segment and was not previously known to play a role in
      rhomboid function. These findings highlight the utility of the activity-based
      protein profiling approach for the characterization of rhomboid function.

PMID- 22963264
TI  - Understanding India, globalisation and health care systems: a mapping of research
      in the social sciences.
AB  - National and transnational health care systems are rapidly evolving with current
      processes of globalisation. What is the contribution of the social sciences to an
      understanding of this field? A structured scoping exercise was conducted to
      identify relevant literature using the lens of India - a 'rising power' with a
      rapidly expanding healthcare economy. A five step search and analysis method was
      employed in order to capture as wide a range of material as possible. Documents
      published in English that met criteria for a social science contribution were
      included for review. Via electronic bibliographic databases, websites and hand
      searches conducted in India, 113 relevant articles, books and reports were
      identified. These were classified according to topic area, publication date,
      disciplinary perspective, genre, and theoretical and methodological approaches.
      Topic areas were identified initially through an inductive approach, then
      rationalised into seven broad themes. Transnational consumption of health
      services; the transnational healthcare workforce; the production, consumption and
      trade in specific health-related commodities, and transnational diffusion of
      ideas and knowledge have all received attention from social scientists in work
      related to India. Other themes with smaller volumes of work include new global
      health governance issues and structures; transnational delivery of health
      services and the transnational movement of capital. Thirteen disciplines were
      found represented in our review, with social policy being a clear leader,
      followed by economics and management studies. Overall this survey of India
      related work suggests a young and expanding literature, although hampered by
      inadequacies in global comparative data, and by difficulties in accessing
      commercially sensitive information. The field would benefit from further cross
      fertilisation between disciplines and greater application of explanatory theory.
      Literatures around stem cell research and health related commodities provide some
      excellent examples of illuminating social science. Future research agendas on
      health systems issues need to include innovative empirical work that captures the
      dynamics of transnational processes and that links macro-level change to fine
      grained observations of social life.

PMID- 22963265
TI  - Biomarker positive and negative subjects in the ADNI cohort: clinical
      characterization.
AB  - BACKGROUND: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was created to
      develop standards for brain imaging and biomarkers for diagnosis and treatment
      trials. Using the ADNI dataset, experts have found that low cerebrospinal fluid
      amyloid-beta1-42 (CSF Abeta1-42) concentration and high total-tau/Abeta1-42 ratio
      are highly predictive of progression in amnestic mild cognitive impairment
      (aMCI), and recommended these biomarkers to support the diagnosis of prodromal
      Alzheimer's disease and select patients for clinical trials. However, biomarker
      selection criteria may introduce systematic bias that undermines their utility.
      METHODS: We tested for systematic biases among individuals undergoing lumbar
      puncture in the ADNI dataset who fulfilled the following entry criteria: (1) aMCI
      with CSF Abeta1-42 <= 192 pG/mL, compared to aMCI with Abeta1-42 > 192 pG/mL, and
      (2) aMCI with total-tau/Abeta1-42 > 0.39, compared to aMCI with total-tau/Abeta1
      42 <= 0.39, as well as comparisons between participants with aMCI with and
      without lumbar puncture. FINDINGS: Individuals with low CSF Abeta1-42 scored
      significantly poorer than individuals with high Abeta1-42 on several baseline
      measures of disease severity, including Logical Memory II (3.24 vs 4.73; p <
      0.001), Functional Activities Questionnaire (4.30 vs 2.37; p < 0.001), and
      Alzheimer's Disease Assessment Scale-cognitive (12.23 vs 10.09; p=0.002). Similar
      results were found using high total-tau/Abeta1-42. No differences were found for
      individuals with and without lumbar puncture except for marital status.
      INTERPRETATIONS: Individuals with aMCI with low Abeta1-42 in the ADNI dataset
      appear to have more advanced disease than those with high Abeta1-42. Selection
      criteria based on ADNI, as well as design of future studies, must account for
      potential confounds between biomarker status and disease severity to ensure that
      the former, and not the latter, is the true determinant of predictive accuracy.

PMID- 22963266
TI  - Concealment tactics among HIV-positive nurses in Uganda.
AB  - This paper is based on two-and-a-half years of ethnographic fieldwork in two
      rural Ugandan health centres during a period of ART scale-up. Around one-third of
      the nurses in these two sites were themselves HIV-positive but most concealed
      their status. We describe how a group of HIV-positive nurses set up a secret
      circle to talk about their predicament as HIV-positive healthcare professionals
      and how they developed innovative care technologies to overcome the skin rashes
      caused by ART that threatened to give them away. Together with patients and a
      traditional healer, the nurses resisted hegemonic biomedical norms denouncing
      herbal medicines and then devised and advocated for a herbal skin cream treatment
      to be included in the ART programme.

PMID- 22963267
TI  - Modulation of a pre-existing conformational equilibrium tunes adenylate kinase
      activity.
AB  - Structural plasticity is often required for distinct microscopic steps during
      enzymatic reaction cycles. Adenylate kinase from Escherichia coli (AK(eco))
      populates two major conformations in solution; the open (inactive) and closed
      (active) state, and the overall turnover rate is inversely proportional to the
      lifetime of the active conformation. Therefore, structural plasticity is
      intimately coupled to enzymatic turnover in AK(eco). Here, we probe the open to
      closed conformational equilibrium in the absence of bound substrate with NMR
      spectroscopy and molecular dynamics simulations. The conformational equilibrium
      in absence of substrate and, in turn, the turnover number can be modulated with
      mutational- and osmolyte-driven perturbations. Removal of one hydrogen bond
      between the ATP and AMP binding subdomains results in a population shift toward
      the open conformation and a resulting increase of k(cat). Addition of the
      osmolyte TMAO to AK(eco) results in population shift toward the closed
      conformation and a significant reduction of k(cat). The Michaelis constants
      (K(M)) scale with the change in k(cat), which follows from the influence of the
      population of the closed conformation for substrate binding affinity. Hence,
      k(cat) and K(M) are mutually dependent, and in the case of AK(eco), any
      perturbation that modulates k(cat) is mirrored with a proportional response in
      K(M). Thus, our results demonstrate that the equilibrium constant of a pre
      existing conformational equilibrium directly affects enzymatic catalysis. From an
      evolutionary perspective, our findings suggest that, for AK(eco), there exists
      ample flexibility to obtain a specificity constant (k(cat)/K(M)) that
      commensurate with the exerted cellular selective pressure.

PMID- 22963268
TI  - A new dimeric naphthoquinone from Diospyros anisandra.
AB  - From the hexane extract of stem bark of Diospyros anisandra was isolated a new
      plumbagin dimer, epoxide of zeylanone, along with 14 known compounds, including
      seven naphthoquinones, four triterpenoids and three sesquiterpenoids. The
      structures were elucidated by the application of IR, UV, MS, 1D- and 2D-NMR
      spectroscopic analysis and by comparison with literature data. 

PMID- 22963269
TI  - Midtrimester amniotic fluid concentrations of angiogenic factors in relation to
      maternal, gestational and neonatal characteristics in normal pregnancies.
AB  - OBJECTIVE: To describe associations among maternal/gestational/neonatal
      characteristics and midpregnancy amniotic fluid concentrations of the main
      angiogenic markers vascular endothelial growth factor (VEGF) and placental growth
      factor (PlGF). METHODS: In a cohort of 206 normal full-term pregnancies,
      midpregnancy amniotic fluid VEGF and PlGF reference values were recorded.
      Possible associations among the above concentrations and various parameters, such
      as maternal age and body mass index, race, parity, smoking, gestational age,
      delivery mode, birth-weight and fetal gender were investigated. RESULTS:
      Midpregnancy amniotic fluid concentrations of both VEGF and PlGF increased with
      increasing gestational age (r = 0.173, p = 0.013 and r = 0.255, p < 0.001,
      respectively), whereas PlGF concentrations positively correlated with birth
      weight (r = 0.154, p = 0.027). The effect of the other above-mentioned parameters
      on VEGF and PlGF concentrations was not significant. CONCLUSIONS: In normal
      pregnancies, midgestation amniotic fluid VEGF and PlGF concentrations positively
      correlate with gestational age. Furthermore, midgestation amniotic fluid PlGF
      concentrations may be a predictor of neonatal birth weight.

PMID- 22963270
TI  - Effect of yoga on serum homocysteine and nitric oxide levels in adolescent women
      with and without dysmenorrhea.
AB  - BACKGROUND: The purpose of the present study is to explore the effect of yoga on
      the serum levels of homocysteine and nitric oxide (NO) in a cohort of women with
      primary dysmenorrhea and normal healthy controls. METHODS: A prospective
      controlled trial was conducted in 35 women with primary dysmenorrhea and 35
      healthy controls in a community-based study. Short-form Menstrual Distress
      Questionnaires (MDQs) were administered to assess the menstrual symptoms. All
      participants were provided yoga intervention, twice a week at 30 minutes/session,
      consecutively for 8 weeks. Blood samples were drawn from each woman on the third
      day of the menstrual cycle. Assessments of MDQs and blood samples for the
      determination of homocysteine and NO concentrations were performed at baseline
      and within the first 3 days of their next menses after completion of yoga
      intervention. RESULTS: A total of 30 women from the dysmenorrheal group and 30
      from the control group completed the study. Homocysteine levels were higher in
      those with dysmenorrhea when compared with healthy controls before yoga
      intervention (Mann-Whitney U test, p<0.05); however, no statistically significant
      differences were found between the two groups after 8 weeks of yoga training
      (p<0.05). The concentrations of homocysteine in both the dysmenorrheal and
      control groups after 8 weeks decreased by 51.37% and 46.46%, respectively
      (p<0.001). There were no statistically significant differences in NO levels
      between the two groups at baseline and after intervention. The total scores on
      the MDQs decreased significantly after yoga intervention in the dysmenorrheal
      group (p<0.05). CONCLUSIONS: Yoga intervention was found to be associated with
      reductions in severity of dysmenorrhea and may be effective in lowering serum
      homocysteine levels after an intervention period of 8 weeks. These observations
      suggest that yoga may have therapeutic effects in women by restoring endothelial
      function.

PMID- 22963271
TI  - Effects of a homeopathic combination remedy on the acute stress response, well
      being, and sleep: a double-blind, randomized clinical trial.
AB  - OBJECTIVES: Stress impacts on health, causing stress-related illness. The aim of
      this study was to investigate stress dampening effects of the homeopathic
      combination remedy dysto-loges((r)) S on physiological and psychological measures
      during acute stress. Additionally, effects of the substance on sleep and life
      quality were investigated. DESIGN: This randomized, double-blind, placebo
      controlled single center study had a total duration of 15 days for each
      participant. SETTING/LOCATION: The study was performed by Daacro, Trier, Germany.
      SUBJECTS: We included 40 women aged 30-50 years that regularly experienced
      impaired well-being when feeling stressed. INTERVENTION: Participants took three
      tablets daily for 14 days. On the final study day, participants took three pills
      in the morning and upon arrival at the study site. Thereafter, the Trier Social
      Stress Test (TSST) was performed. OUTCOME MEASURES: Primary endpoints were saliva
      cortisol responses to the stress test. Secondary biological endpoints were plasma
      cortisol, adrenocorticotrophic hormone, epinephrine, and norepinephrine (NE) and
      heart rates. Psychological secondary endpoints were well-being, anxiety, stress,
      and insecurity during the stress test as well as sleep and quality of life.
      RESULTS: Stress-induced cortisol levels did not differ between groups, but verum
      treated participants were characterized by lower NE levels. Two weeks of
      treatment with the homeopathic substance resulted in a better sleep quality.
      Sleep improvement was associated with a higher hormonal response to the TSST in
      both groups. In addition, individuals with impaired sleep in the placebo group
      had higher unstimulated NE levels. CONCLUSIONS: This study provides preliminary
      evidence for beneficial effects of dysto-loges S on sleep quality. Improvement of
      sleep quality was positively associated with a normalized neuroendocrine stress
      response during acute stress, whereas an altered hormonal response was observed
      in participants with impaired sleep. We hypothesize that the test product may
      possibly reduce NE release.

PMID- 22963273
TI  - Vibration spectroscopy of a sessile drop and its contact line.
AB  - Resonance frequencies of small sessile liquid drops (1-20 MUL) were estimated
      from the power spectra of their height fluctuations after subjecting them to
      white noise vibration. Various resonance modes could be identified with this
      method as a function of the mass of the drop. Studies with water drops on such
      supports as polystyrene (theta ~ 80 degrees ) and a superhydrophobic surface of
      microfibrillar silicone rubber (theta ~ 162 degrees ) demonstrated that the
      resonant frequency decreases with the contact angle, theta. This trend is in
      remarkable agreement with the current models of the resonant vibration of sessile
      drops. A novel aspect of this study is the analysis of the modes of a slipping
      contact line that indicated that its higher frequency modes are more severely
      damped than its lower ones. Another case is with the glycerol-water solutions,
      where the resonance frequency decreases with the concentration of glycerol purely
      due to the capillary effects. The interface fluctuation, on the other hand, is
      strongly correlated with the kinematic viscosity of the liquid. Thus, these
      experiments provide a means to measure the surface tension and the viscosity of
      very small droplets.

PMID- 22963272
TI  - Tracing genomic variations in two highly virulent Yersinia enterocolitica strains
      with unequal ability to compete for host colonization.
AB  - BACKGROUND: Yersinia enterocolitica is a gastrointestinal foodborne pathogen
      found worldwide and which especially affects infants and young children. While
      different bioserotypes have been associated with varying pathogenicity, research
      on Y. enterocolitica is mainly conducted on the highly virulent mouse-lethal
      strains of biotype 1B and serotype O:8. We demonstrate here that two Y.
      enterocolitica bioserotype 1B/O:8 strains, 8081 and WA-314, display different
      virulence and fitness properties in a mouse model. In vivo co-infection
      experiments revealed that strain WA-314 overcomes strain 8081 in the colonization
      of spleen and liver. To trace the reasons of this incongruity, we present here
      the first high-quality sequence of the whole genome of strain WA-314 and compare
      it to the published genome of strain 8081. RESULTS: Regions previously accepted
      as unique to strain 8081, like the YAPI and YGI-3 genomic islands, are absent
      from strain WA-314, confirming their strain-specificity. On the other hand, some
      fitness- and bacterial competition-associated features, such as a putative
      colicin cluster and a xenobiotic-acyltransferase-encoding gene, are unique to
      strain WA-314. Additional acquisitions of strain WA-314 are seven prophage-like
      regions. One of these prophages, the 28-kb P4-like prophage YWA-4, encodes a PilV
      like protein that may be used for adhesion to and invasion of the intestinal
      cells. Furthermore, a putative autotransporter and two type 1 fimbrial proteins
      of strain WA-314 show a sequence similarity <50% with the orthologous proteins in
      strain 8081. The dissimilar sequences of these proteins indicate possible
      different functions or interaction modes, reflecting the specific adhesion
      properties of Y. enterocolitica strains 8081 and WA-314 and thus the different
      efficiency of host colonization. Further important differences were found in two
      pYV plasmid-encoded virulence factors, YopM and YscP. The impact of these
      differences on virulence is discussed. CONCLUSIONS: Our study emphasizes that the
      virulence of pathogens can be increased, by acquiring new genes and/or improving
      the function of essential virulence proteins, resulting in permanently hyper
      virulent strains. This work also highlights the importance of addressing genetic
      and phenotypic variations among closely related bacterial strains, even those
      belonging to the same bioserotype.

PMID- 22963274
TI  - A case of near-fatal fenpyroximate intoxication: the role of percutaneous
      cardiopulmonary support and therapeutic hypothermia.
AB  - INTRODUCTION: Fenpyroximate is a potent inhibitor of the mitochondrial proton
      translocating NADH-quinone oxidoreductase (complex I). Although it is widely used
      as an acaricide, data on the acute toxicity of fenpyroximate in humans are very
      limited. CASE DETAIL: A 44-year-old woman was brought to our hospital with a
      reduced level of consciousness, hypotension, and severe lactic acidosis after
      deliberate ingestion of 5% fenpyroximate solution. The acidosis progressively
      deteriorated despite maximal supportive treatment, and cardiac arrest refractory
      to standard cardiopulmonary resuscitation developed. The patient was successfully
      resuscitated with percutaneous cardiopulmonary support, therapeutic hypothermia,
      and intravenous acetylcysteine. Blood gases of simultaneously obtained arterial
      and central venous blood revealed decreased arteriovenous oxygen difference.
      DISCUSSION: The present case, along with previous cases of fatal complex I
      inhibitor poisoning, indicates that impaired oxygen utilization at the tissue
      level is the major mechanism underlying the fatality of this condition.
      Percutaneous cardiopulmonary support may help restore vital organ perfusion by
      increasing oxygen delivery even in the presence of decreased oxygen consumption,
      thereby allowing additional time for recovery and drug metabolism. Therapeutic
      hypothermia also may be beneficial in treating severe complex I inhibitor
      poisoning, since hypothermia itself attenuates oxidative processes and decreases
      the metabolic rate.

PMID- 22963275
TI  - In vivo decontamination of the nerve agent VX using the domestic swine model.
AB  - The purpose of this in vivo study was to assess a new, putatively optimised
      method for mass casualty decontamination ("ORCHIDS protocol") for effectiveness
      in removing the chemical warfare agent VX from the skin of anaesthetised,
      domestic white pigs. ORCHIDS protocol consists of a 1.5-minute shower with a mild
      detergent (ArgosTM) supplemented by physical removal. A standard method of wet
      decontamination was used for comparison. Experimental animals were divided into
      four groups (A-D). Two groups were exposed to a supra-lethal percutaneous dose (5
      * LD(50); 300 MUg kg(-1)) of VX for 1 h prior to decontamination with either the
      ORCHIDS (C) or standard protocol (D). A third (B, positive control) group was
      exposed but not subject to decontamination. Blank controls (A) received
      anaesthesia and the corresponding dose of normal saline instead of VX.
      Observations of the clinical signs of intoxication were supplemented by
      measurements of whole blood cholinesterase (ChE) performed on samples of arterial
      blood acquired at 30-minute intervals for the duration of the study (up to 6 h).
      Untreated (B) animals displayed typical cholinergic signs consistent with VX
      intoxication (local fasciculation, mastication, salivation, pilo-erection and
      motor convulsions) and died 165-240 min post exposure. All animals in both
      decontamination treatment groups (C, D) survived the duration of the study and
      exhibited less severe signs of cholinergic poisoning. Thus, both the standard and
      ORCHIDS protocol were demonstrably effective against exposure to the potent nerve
      agent VX, even after a delay of 1 h. A critical advantage of the ORCHIDS protocol
      is the relatively short shower duration (11/2 min compared to 3 min). In
      practice, this could substantially improve the rate at which individuals could be
      decontaminated by emergency responders following exposure to toxic materials such
      as chemical warfare agents.

PMID- 22963276
TI  - Pollen limitation and Allee effect related to population size and sex ratio in
      the endangered Ottelia acuminata (Hydrocharitaceae): implications for
      conservation and reintroduction.
AB  - Small populations may suffer more severe pollen limitation and result in Allee
      effects. Sex ratio may also affect pollination and reproduction success in
      dioecious species, which is always overlooked when performing conservation and
      reintroduction tasks. In this study, we investigated whether and how population
      size and sex ratio affected pollen limitation and reproduction in the endangered
      Ottelia acuminata, a dioecious submerged species. We established experimental
      plots with increasing population size and male sex ratio. We observed insect
      visitation, estimated pollen limitation by hand-pollinations and counted fruit
      set and seed production per fruit. Fruit set and seed production decreased
      significantly in small populations due to pollinator scarcity and thus suffered
      more severe pollen limitation. Although frequently visited, female-biased larger
      populations also suffered severe pollen limitation due to few effective visits
      and insufficient pollen availability. Rising male ratio enhanced pollination
      service and hence reproduction. Unexpectedly, pollinator preferences did not
      cause reduced reproduction in male-biased populations because of high pollen
      availability. However, reproductive outputs showed more variability in severe
      male-biased populations. Our results revealed two component Allee effects in
      fruit set and seed production, mediated by pollen limitation in O. acuminata.
      Moreover, reproduction decreased significantly in larger female-biased
      populations, increasing the risk of an Allee effect.

PMID- 22963277
TI  - Therapeutic implications of adding the psychotropic drug escitalopram in the
      treatment of patients suffering from moderate-severe psoriasis and psychiatric
      comorbidity: a retrospective study.
AB  - BACKGROUND: It is known that stress and/or psychiatric diseases can play an
      important role in determining psoriasis, including the well-known negative somato
      psychiatric rebound that comes with the disease. METHODS: Samples of 38 subjects
      suffering from both moderate-severe psoriasis treated with anti-TNFalpha, and
      depressive and/or anxious mood disorders were studied. Part of them were
      additionally treated with escitalopram, whereas the other group only consulted to
      a dermatological and psychiatric follow-up. The aim of this study was to
      determine if an improvement in the dermatological manifestation as well as an
      improvement in the anxious-depressive disorder can be observed. RESULTS: The
      study revealed that patients treated with escitalopram had a reduction of psycho
      diagnostic test scores that measure depression and anxiety levels as well as the
      values of pruritus. CONCLUSION: Our study suggests that psychological
      interventions and antidepressant medications may improve perceived symptom
      severity, quality of life and major compliance to the treatment in selected
      patients (suffering from psoriasis and mood disturbance), without a clinician
      necessarily being able to see an impact on psoriasis severity.

PMID- 22963278
TI  - Is there a link between blastomere contact surfaces of day 3 embryos and live
      birth rate?
AB  - BACKGROUND: Cell-cell communication and adhesion are essential for the compaction
      process of early stage embryos. The aim of this study was to develop a non
      invasive objective calculation system of embryo compaction in order to test the
      hypothesis that embryos with a larger mean contact surface result in a higher
      live birth rate compared to embryos with a lower mean contact surface. METHODS:
      Multilevel images of 474 embryos transferred on day 3 were evaluated by the
      Cellify software. This software calculates the contact surfaces between the
      blastomeres. The primary outcome of this study was live birth. An ideal range of
      contact surface was determined and the positive and negative predictive value,
      the sensitivity, the specificity and the area under the curve for this new
      characteristic were calculated. RESULTS: In total, 115 (24%) transferred embryos
      resulted in a live birth. Selection of an embryo for transfer on its mean contact
      surface could predict live birth with a high sensitivity (80%) and high negative
      predicting value (83%) but with a low positive predictive value (27%), a low
      specificity (31%) and low area under the ROC curve (0.56). The mean contact
      surface of embryos cultured in a single medium was significantly higher compared
      to the mean contact surface of embryos cultured in a sequential medium (p =
      0.0003). CONCLUSIONS: Neither the mean contact surface nor the number of contact
      surfaces of a day 3 embryo had an additional value in the prediction of live
      birth. The type of culture medium, however, had an impact on the contact surface
      of an embryo. Embryos cultured in a single medium had a significant larger
      contact surface compared to embryos cultured in the sequential medium.

PMID- 22963279
TI  - Body satisfaction and sexual health in Dutch female university students.
AB  - Studies in the field of body image have primarily addressed its negative aspects,
      such as body dissatisfaction. The present study focused instead on women who are
      satisfied with their bodies and on how body satisfaction relates to sexual
      health. A sample of 319 Dutch female university students completed an online
      survey that included items about body image evaluation, body image investment,
      overweight preoccupation, body image affect during sexual activity, sexual
      frequency, sexual functioning, and sexual self-esteem. We found that the level of
      body dissatisfaction was minimal in our sample. The majority reported neutral or
      mildly positive body evaluations, and in 30% of the sample these evaluations were
      clearly positive. Comparisons between women who reported positive versus neutral
      body evaluations showed that the body-satisfied women had lower body mass indexes
      (BMIs) and reported less body image investment, less overweight preoccupation,
      and less body self-consciousness during sexual activity. With regard to sexual
      health, they reported higher sexual self-esteem and better sexual functioning.
      Furthermore, we found that body image self-consciousness was negatively
      associated with sexual functioning, sexual self-esteem, and frequency of sexual
      activity with a partner. Body satisfaction did not account for a portion of the
      relationship of body self-consciousness during sexual activity with sexual
      health. 

PMID- 22963280
TI  - Postnatal neurogenesis and dopamine alterations in early psychosis.
AB  - Schizophrenia is most likely a neurodevelopmental disorder with a characteristic
      delayed onset of symptoms occurring usually during transition from adolescence to
      adulthood. Recent studies revealed that both genetic and environmental risk
      factors for the disease disturb not only embryonic, but also postnatal
      neurogenesis, possible contributing to neurochemical alterations associated with
      schizophrenia. Several recent patents proposed therapeutic interventions in
      schizophrenia by increasing postnatal neurogenesis. It remains, however, unclear,
      how such pro-neurogenic interventions could ameliorate alterations in
      neurotransmitter systems associated with the disease, such as the dopamine
      system. Here we review these patents in the context of the existent data about
      postnatal neurogenesis in the subventricular zone in rodents and primates. We
      discuss also in light of a recently proposed theoretical model the possible
      relevance of disturbed neurogenesis for the dopamine system, focusing on the
      dopamine receptors associated with neurogenesis, the D3 receptors, and a D3
      expressing structure derived from the subventricular zone, the Islands of
      Calleja. Finally, we discuss these findings in the light of molecular imaging
      studies in early schizophrenia.

PMID- 22963282
TI  - Evaluation of the in vivo anti-inflammatory and analgesic activity of a highly
      water-soluble aspirin conjugate.
AB  - Glucose-aspirin (GA) was synthesized by conjugating aspirin (ASA) to the 3-carbon
      of glucose to produce a stable water-soluble aspirin derivative. The in vivo
      activities were compared with those of aspirin. The mouse tail flick assay showed
      that at 120 min., both aspirin and GA showed the maximum possible effect, and the
      higher dose (200 mg/kg) generally had less of an effect than the lower dose (100
      mg/kg). Per cent inhibition of paw oedema was 63% and 69% for ASA and GA at 100
      mg/kg, respectively. In the tail immersion test, the increase in reaction time
      was significantly greater with GA as compared to aspirin (100 mg/kg) at 60 min.
      In conclusion, there was significant anti-inflammatory and analgesic activity for
      GA at the doses studied under the experimental conditions.

PMID- 22963281
TI  - Astrocytic 5-HT(2B) receptor as in vitro and in vivo target of SSRIs.
AB  - Most studies in this journal describe recent patents. The present study only has
      one such reference. Instead, we hope that its contents will trigger investigation
      of antidepressant drugs along the suggested lines and lead to ensuing patent
      applications - first and foremost by more focus on astrocytes. Clinical research
      has already pointed towards the importance of these cells, which account for one
      quarter of brain cortical volume and at least as much of its oxidative
      metabolism. Astrocytes express a multitude of receptors, including 5-HT(2B)
      receptors. In cultured astrocytes acute treatment with any of the five SSRIs,
      fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram, stimulates
      equipotently and with sufficient affinity to be therapeutically relevant, the 5
      HT(2B) receptor. Following EGF receptor transactivation and a resultant autocrine
      HB-EGF stimulation, these drugs activate two interdependent signal pathways i)
      the Ras-Raf-Mek-ERK phosphorylation pathway and ii) the PI3K-AKT-GSK-3beta
      pathway, eventually altering gene expression. Chronic treatment with fluoxetine
      upregulates gene expression of cPLA2, ADAR2, GluK2 and 5-HT(2B) receptors, and
      RNA editing of the later two in cultured astrocytes and in astrocytes obtained by
      fluorescence-activated cell sorting of cells from fluoxetinetreated mice. Chronic
      treatment also down-regulates the Gq-protein-coupled receptor-induced increase of
      intracellular Ca2+ by inhibiting TRPC function, compromising astrocytic Ca2+ re
      filling. This affects glycogenolysis and several steps in the signal pathways.
      Since astrocytes in the mature brain and in our cultures do not express SERT,
      both acute and chronic effects in cultured astrocytes must be directly mediated
      by 5-HT(2B) receptor activation.

PMID- 22963283
TI  - Evaluation of supply-side initiatives to improve access to coronary bypass
      surgery.
AB  - BACKGROUND: Guided by the evidence that delaying coronary revascularization may
      lead to symptom worsening and poorer clinical outcomes, expansion in cardiac
      surgery capacity has been recommended in Canada. Provincial governments started
      providing one-time and recurring increases in budgets for additional open heart
      surgeries to reduce waiting times. We sought to determine whether the year of
      decision to proceed with non-emergency coronary bypass surgery had an effect on
      time to surgery. METHODS: Using records from a population-based registry, we
      studied times between decision to operate and the procedure itself. We estimated
      changes in the length of time that patients had to wait for non-emergency
      operation over 14 calendar periods that included several years when supplementary
      funding was available. We studied waiting times separately for patients who
      access surgery through a wait list and through direct admission. RESULTS: During
      two periods when supplementary funding was available, 1998-1999 and 2004-2005,
      the weekly rate of undergoing surgery from a wait list was, respectively, 50% and
      90% higher than in 1996-1997, the period with the longest waiting times. We also
      observed a reduction in the difference between 90th and 50th percentiles of the
      waiting-time distributions. Forty percent of patients in the 1998, 1999, 2004 and
      2005 cohorts (years when supplementary funding was provided) underwent surgery
      within 16 to 20 weeks following the median waiting time, while it took between 27
      and 37 weeks for the cohorts registered in the years when supplementary funding
      was not available. Times between decision and surgery were shorter for direct
      admissions than for wait-listed patients. Among patients who were directly
      admitted to hospital, time between decision and surgery was longest in 1992-1993
      and then has been steadily decreasing through the late nineties. The rate of
      surgery among these patients was the highest in 1998-1999, and has not changed
      afterwards, even for years when supplementary funding was provided. CONCLUSIONS:
      Waiting times for non-emergency coronary bypass surgery shortened after
      supplementary funding was granted to increase volume of cardiac surgical care in
      a health system with publicly-funded universal coverage for the procedure. The
      effect of the supplementary funding was not uniform for patients that access the
      services through wait lists and through direct admission.

PMID- 22963285
TI  - Insertion of a hydroxido bridge into a diphenoxido dinuclear copper(II) complex:
      drastic change of the magnetic property from strong antiferromagnetic to
      ferromagnetic and enhancement in the catecholase activity.
AB  - A diphenoxido-bridged dinuclear copper(II) complex, [Cu(2)L(2)(ClO(4))(2)] (1),
      has been synthesized using a tridentate reduced Schiff base ligand, 2-[[2
      (diethylamino)ethylamino]methyl]phenol (HL). The addition of triethylamine to the
      methanolic solution of this complex produced a novel triple bridged (double
      phenoxido and single hydroxido) dinuclear copper(II) complex,
      [Cu(2)L(2)(OH)]ClO(4) (2). Both complexes 1 and 2 were characterized by X-ray
      structural analyses, variable-temperature magnetic susceptibility measurements,
      and spectroscopic methods. In 1, the two phenoxido bridges are equatorial
      equatorial and the species shows strong antiferromagnetic coupling with J = 
      615.6(6.1) cm(-1). The inclusion of the equatorial-equatorial hydroxido bridge in
      2 changes the Cu...Cu distance from 3.018 A (avg.) to 2.798 A (avg.), the
      positions of the phenoxido bridges to axial-equatorial, and the magnetic coupling
      to ferromagnetic with J = 50.1(1.4) cm(-1). Using 3,5-di-tert-butylcatechol as
      the substrate, the catecholase activity of the complexes has been studied in a
      methanol solution; compound 2 shows higher catecholase activity (k(cat) = 233.4
      h(-1)) than compound 1 (k(cat) = 93.6 h(-1)). Both complexes generate identical
      species in solution, and they are interconvertible simply by changing the pH of
      their solutions. The higher catecholase activity of 2 seems to be due to the
      presence of the OH group, which increases the pH of its solution.

PMID- 22963284
TI  - Spontaneous rearrangement of the beta20/beta21 strands in simulations of
      unliganded HIV-1 glycoprotein, gp120.
AB  - Binding of the viral spike drives cell entry and infection by HIV-1 to the
      cellular CD4 and chemokine receptors with associated conformational change of the
      viral glycoprotein envelope, gp120. Crystal structures of the CD4-gp120-antibody
      ternary complex reveal a large internal gp120 cavity formed by three domains-the
      inner domain, outer domain, and bridging sheet domain-and are capped by CD4
      residue Phe43. Several structures of gp120 envelope in complex with various
      antibodies indicated that the bridging sheet adopts varied conformations. Here,
      we examine bridging sheet dynamics using a crystal structure of gp120 bound to
      the F105 antibody exhibiting an open bridging sheet conformation and with an
      added V3 loop. The two strands of the bridging sheet beta2/beta3 and
      beta20/beta21 are dissociated from each other and are directed away from the
      inner and outer domains. Analysis of molecular dynamics (MD) trajectories
      indicates that the beta2/beta3 and beta20/beta21 strands rapidly rearrange to
      interact with the V3 loop and the inner and outer domains, respectively. Residue
      N425 on beta20 leads the conformational rearrangement of the beta20/beta21
      strands by interacting with W112 on the inner domain and F382 on the outer
      domain. An accompanying shift is observed in the inner domain as helix alpha1
      exhibits a loss in helicity and pivots away from helix alpha5. The two
      simulations provide a framework for understanding the conformational diversity of
      the bridging sheet and the propensity of the beta20/beta21 strand to refold
      between the inner and outer domains of gp120, in the absence of a bound ligand.

PMID- 22963286
TI  - Uptake and effects of microplastics on cells and tissue of the blue mussel
      Mytilus edulis L. after an experimental exposure.
AB  - In this study, we investigated if industrial high-density polyethylene (HDPE)
      particles, a model microplastic free of additives, ranging > 0-80 MUm are
      ingested and taken up into the cells and tissue of the blue mussel Mytilus edulis
      L. The effects of exposure (up to 96 h) and plastic ingestion were observed at
      the cellular and subcellular level. Microplastic uptake into the gills and
      digestive gland was analyzed by a new method using polarized light microscopy.
      Mussel health status was investigated incorporating histological assessment and
      cytochemical biomarkers of toxic effects and early warning. In addition to being
      drawn into the gills, HDPE particles were taken up into the stomach and
      transported into the digestive gland where they accumulated in the lysosomal
      system after 3 h of exposure. Our results show notable histological changes upon
      uptake and a strong inflammatory response demonstrated by the formation of
      granulocytomas after 6 h and lysosomal membrane destabilization, which
      significantly increased with longer exposure times. We provide proof of principle
      that microplastics are taken up into cells and cause significant effects on the
      tissue and cellular level, which can be assessed with standard cytochemical
      biomarkers and polarized light microscopy for microplastic tracking in tissue.

PMID- 22963287
TI  - Patient safety in India: time to speed up our efforts to reduce avoidable harm.

PMID- 22963288
TI  - Pathological complete response in locally advanced breast cancer: determinants
      and predictive significance.
AB  - BACKGROUND: Neoadjuvant chemotherapy is now the standard approach for most large
      breast cancers including locally advanced cancers of the breast. The majority of
      patients respond satisfactorily to chemotherapy with effective downsizing of
      tumours to consider breast conservation surgery. Pathological complete response
      (pathCR) is known to be a strong predictor of good outcome; however, many factors
      are known to influence the extent of response to chemotherapy. It has been
      observed that smaller the tumour, better is the response achieved in contrast to
      larger and locally advanced tumours where only one-third may respond well enough
      to merit breast conservation. Various other clinical, biological and molecular
      factors are also being evaluated as effective predictors of chemosensitivity.
      Most of these are either not easily available for all patients in developing
      countries or are overtly expensive and not applicable for all patients. METHODS:
      We evaluated the clinical and pathological predictors of response to chemotherapy
      in 1402 women with locally advanced breast cancer. RESULTS: There was a higher
      rate of pathCR in smaller tumours, younger women and ER-negative as well as
      triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and
      lymphatic and vascular invasion (LVI) were associated with lower pathCR.
      CONCLUSION: In the absence of ready availability of expensive molecular and
      genomic assays, clinical parameters and standard histopathological variables can
      also be useful indicators of response to neoadjuvant chemotherapy. Additionally,
      they can help identify those who could be eventually conserved or have a better
      outcome.

PMID- 22963289
TI  - Interdistrict variations in child health status and health services utilization:
      lessons for health sector priority setting and planning from a cross-sectional
      survey in rural India.
AB  - BACKGROUND: There are limited data on interdistrict variations in child health
      status and health services utilization within the states of India. We conducted
      this study to identify and understand district-wise variations in child
      morbidity, mortality, healthcare seeking, and the status of health facilities in
      India. METHODS: A cross-sectional population-based cluster survey was conducted
      from April to July 2007 in 16 districts of eight states in India. Two districts
      with similar demographic profile and health criteria were selected from each
      study state. RESULTS: A total of 216 794 households and 24 812 under-5 children
      were surveyed. There were wide interdistrict variations in the health status of
      children within the same state and between different states across India.
      Interdistrict difference of >5 points/1000 live-births was found for infant
      mortality rate and under-5 mortality rate in all eight study states, while in six
      out of eight states this difference was >10 points/1000 live-births. Four states
      had a difference of >10 points/1000 live-births between respective districts for
      neonatal mortality rate. The interdistrict differences were also noted in
      childhood morbidity and health-seeking behaviour. Analysis of proportion of
      health facilities conforming to Indian public health standards revealed that the
      difference was m10% for availability of vaccines in five states, emergency
      services in three, laboratory services and logistics in four each, and referral
      facility in three of the eight study states. CONCLUSION: This study underscores
      an important information gap in the country where planners seem to rely heavily
      on a few selected national-level databases that may not be adequate at the micro
      level. The current process of sporadic health surveys also appears inadequate and
      inappropriate. There is a need for district-specific data for planning, improving
      quality of service and generating demand for health service utilization to
      improve child survival in India. The findings of this study may prove useful for
      child health programme planning in India.

PMID- 22963290
TI  - Smokeless tobacco use among patients with tuberculosis in Karnataka: the need for
      cessation services.
AB  - BACKGROUND: India is home to the largest population of patients with tuberculosis
      and tobacco users in the world. Smokeless tobacco use exceeds smoking and is
      increasing. There is no study to date that reports smokeless tobacco use before
      and after the diagnosis and treatment of tuberculosis. We assessed smokeless
      tobacco use among former patients of tuberculosis in Karnataka, India. METHODS:
      We conducted a community-based, cross sectional study among 202 men, who had been
      diagnosed and treated for tuberculosis (mean age 48 years), selected by
      multistage, random sampling. Using a semi-structured interview schedule,
      retrospective smoking and smokeless tobacco use were captured at eight time
      points before and after the diagnosis and treatment of tuberculosis. RESULTS:
      Most patients suspended tobacco use during treatment. A high 44% prevalence of
      smokeless tobacco use 6 months before diagnosis was reduced to just 8% during the
      intensive phase of treatment and climbed to 27% 6 months after treatment. The
      tobacco use relapse rate 6 months after completion of treatment was higher for
      smokeless tobacco use (52%, 95% CI 41%-62%) than for smoking (36%, 95% CI 26%
      45%). We also found that many patients who were advised to quit smoking continued
      using smokeless tobacco after completion of treatment. Additionally, new
      smokeless tobacco use was documented. Of the 11 new exclusive smokeless tobacco
      users, 10 shifted from smoking to smokeless tobacco use as a form of harm
      reduction. CONCLUSION: Patients with tuberculosis are advised by their doctors,
      at the time of diagnosis, to quit smoking. Several patients shift from smoking to
      smokeless tobacco use, which needs to be addressed while providing tobacco
      cessation services.

PMID- 22963291
TI  - An assessment of opinion of Indian physicians about emergency medicine in India.
AB  - BACKGROUND: Emergency medicine (EM) has recently been recognized as a specialty
      in India and formal training programmes are yet to be developed. METHODS: A
      survey was devised to elicit the opinion of recently graduated physicians in
      Chennai, India about EM as well as about the current state of EM in India. A
      convenience sample of 130 respondents filled out a 21-question survey. RESULTS:
      Ninety-four per cent of respondents stated that EM was essential for providing
      quality healthcare; 94% of respondents felt there needs to be a change in
      emergency departments in India, with only 20% stating they were proud of the
      emergency departments in India. Seventy-six per cent of respondents were more
      likely to consider EM if the specialty was recognized by the Medical Council of
      India and 76% were inclined to pursue the specialty if there were more training
      programmes. CONCLUSION: Recently graduated physicians found flaws in the current
      state of emergency care in India; however, overall they remain interested in the
      field of EM.

PMID- 22963292
TI  - Atypical mucocutaneous involvement with Leishmania donovani.
AB  - Mucocutaneous leishmaniasis has rarely been reported from India. The usual
      causative organisms of this infection are Leishmania braziliensis and L. tropica.
      Another species, L. donovani, which usually causes visceral leishmaniasis, has
      recently been reported to cause mucocutaneous disease in a few patients from Sri
      Lanka. We report two patients who had undiagnosed chronic skin lesions for
      several years. Skin biopsies revealed Leishmania and the species was
      characterized as L. donovani in both patients. There was considerable improvement
      in the skin lesions following treatment with liposomal amphotericin B.

PMID- 22963293
TI  - Reuse of single-use devices: looking back, looking forward.
AB  - The reuse of medical devices marked as 'single use' by manufacturers has been
      going on for several decades. The process has been rationalized and legislated in
      the West as well as in Japan. However, the practice continues in an unregulated
      manner in India due to a paucity of guidance from the Food and Drug
      Administration in India. We trace the evolution of reuse policies, look at the
      prevalent practices in the Indian and international contexts, analyse the
      available Indian literature and address the ethical and economic implications of
      reuse. We also suggest some guidelines which may be adopted to formulate
      policies.

PMID- 22963294
TI  - A viable intervention to control hypertension?

PMID- 22963295
TI  - What sustains the market for TB serodiagnostics in India: a novel analysis.

PMID- 22963296
TI  - HPV vaccination: more evidence of benefit.

PMID- 22963297
TI  - Setting up a coagulation laboratory at a district hospital.

PMID- 22963298
TI  - Medical education in India: time to make some changes.
AB  - India is in need of well-trained doctors. We highlight and analyse some of the
      problems affecting medical education in India and their possible solutions. The
      medical education system can be reviewed under four heads: selection of students,
      medical training, evaluation, and the development and accreditation of faculty.
      In India, students enter medical colleges without receiving sufficient
      orientation about the profession. If students were given some exposure to various
      professions in the final years of school, it would help address this issue.
      Medical students are selected on the basis of pre-medical tests consisting of
      multiple-choice questions, the validity of which is being questioned
      increasingly. There is no coordination between the scheduling of lectures on
      various diseases and their management and the clinical exposure of the students.
      Active involvement in treatment is limited to the final year, called internship,
      which is hampered by preparation for postgraduate entrance examinations. Efforts
      should be made to provide hands-on experience at an earlier time in the course. A
      systematic and reliable programme for evaluation is a must. There is a need for a
      shift in the focus of evaluation, which should assess the application of
      knowledge rather than the ability to recall facts. The replacement of the
      traditional long-/short-case examinations with more valid and reliable
      instruments for the assessment of clinical skills should be considered. 'Vision
      2015', a document developed by the Medical Council of India, contains many
      notable recommendations for the improvement of the current system. If these are
      implemented effectively, the impact of improvement in Indian medical education
      will be felt globally.

PMID- 22963299
TI  - Can presumed consent overcome organ shortage in India? Lessons from the Belgian
      experience.

PMID- 22963300
TI  - A roadmap to improve care of patients with breast cancer in India.

PMID- 22963302
TI  - A funeral and a wedding.

PMID- 22963303
TI  - Paradox of plenty: nutrition in New York and New Delphi.

PMID- 22963310
TI  - Lymph node biopsy audit in a private hospital.

PMID- 22963317
TI  - Assessing performance enhancing tools: experiences with the open performance
      review and appraisal system (OPRAS) and expectations towards payment for
      performance (P4P) in the public health sector in Tanzania.
AB  - BACKGROUND: Health workers' motivation is a key determinant of the quality of
      health services, and poor motivation has been found to be an obstacle to service
      delivery in many low-income countries. In order to increase the quality of
      service delivery in the public sector in Tanzania, the Open Performance Review
      and Appraisal System (OPRAS) has been implemented, and a new results-based
      payment system, Payment for performance (P4P) is introduced in the health sector.
      This article addresses health workers' experiences with OPRAS, expectations
      towards P4P and how lessons learned from OPRAS can assist in the implementation
      of P4P. The broader aim is to generate knowledge on health workers' motivation in
      low-income contexts. METHODS: A qualitative study design has been employed to
      elicit data on health worker motivation at a general level and in relation to
      OPRAS and P4P in particular. Focus group discussions (FGDs) and in-depth
      interviews (IDIs) have been conducted with nursing staff, clinicians and
      administrators in the public health sector in a rural district in Tanzania. The
      study has an ethnographic backdrop based on earlier long-term fieldwork in
      Tanzania. RESULTS: Health workers evaluated OPRAS and P4P in terms of the
      benefits experienced or expected from complying with the tools. The study found a
      general reluctance towards OPRAS as health workers did not see OPRAS as leading
      to financial gains nor did it provide feedback on performance. Great expectations
      were expressed towards P4P due to its prospects of topping up salaries, but the
      links between the two performance enhancing tools were unclear. CONCLUSIONS:
      Health workers respond to performance enhancing tools based on whether the tools
      are found appropriate or yield any tangible benefits. The importance placed on
      salary and allowances forms the setting in which OPRAS operates. The expected
      addition to the salary through P4P has created a vigorous discourse among health
      workers attesting to the importance of the salary for motivation. Lessons learned
      from OPRAS can be utilized in the implementation of P4P and can enhance our
      knowledge on motivation and performance in the health services in low-income
      contexts such as Tanzania.

PMID- 22963318
TI  - Systemic delays in the initiation of antiretroviral therapy during pregnancy do
      not improve outcomes of HIV-positive mothers: a cohort study.
AB  - BACKGROUND: Antiretroviral therapy (ART) initiation in eligible HIV-infected
      pregnant women is an important intervention to promote maternal and child health.
      Increasing the duration of ART received before delivery plays a major role in
      preventing vertical HIV transmission, but pregnant women across Africa experience
      significant delays in starting ART, partly due the perceived need to deliver ART
      counseling and patient education before ART initiation. We examined whether
      delaying ART to provide pre-ART counseling was associated with improved outcomes
      among HIV-infected women in Cape Town, South Africa. METHODS: We undertook a
      retrospective cohort study of 490 HIV-infected pregnant women referred to
      initiate treatment at an urban ART clinic. At this clinic all patients including
      pregnant women are screened by a clinician and then undergo three sessions of
      counseling and patient education prior to starting treatment, commonly
      introducing delays of 2-4 weeks before ART initiation. Data on viral suppression
      and retention in care after ART initiation were taken from routine clinic
      records. RESULTS: A total of 382 women initiated ART before delivery (78%); ART
      initiation before delivery was associated with earlier gestational age at
      presentation to the ART service (p < 0.001). The median delay between screening
      and ART initiation was 21 days (IQR, 14-29 days). Overall, 84.7%, 79.6% and 75.0%
      of women who were pregnant at the time of ART initiation were retained in care at
      4, 8 and 12 months after ART initiation, respectively. Among those retained, 91%
      were virally suppressed at each follow-up visit. However the delay from screening
      to ART initiation was not associated with retention in care and/or viral
      suppression throughout the first year on ART in unadjusted or adjusted analyses.
      CONCLUSIONS: A substantial proportion of eligible pregnant women referred for ART
      do not begin treatment before delivery in this setting. Among women who do
      initiate ART, delaying initiation for patient preparation is not associated with
      improved maternal outcomes. Given the need to maximize the duration of ART before
      delivery for prevention of mother-to-child HIV transmission, there is an urgent
      need for new strategies to help expedite ART initiation in eligible pregnant
      women.

PMID- 22963319
TI  - Improvement of palmoplantar pustulosis by mizoribine.

PMID- 22963320
TI  - Three bioactive sesquiterpene quinones from the Fijian marine sponge of the genus
      Hippospongia.
AB  - A sesquiterpenoid quinone, epi-ilimaquinone (1), and two sesquiterpene amino
      quinones, smenospongine (2) and glycinylilimaquinone (3), were isolated from the
      Fijian marine sponge Hippospongia sp. The structures of these compounds were
      determined by spectroscopic analysis. Compounds 1 and 3 were reported for the
      first time in this study from the sponge of the genus Hippospongia. Compound 1
      displayed potent cytotoxic activity and showed antibacterial activity against
      methicillin-resistant Staphylococcus aureus, wild type S. aureus and vancomycin
      resistant Enterococcus faecium and displayed antifungal activity against
      amphotericin-resistant Candida albicans while compounds 2 and 3 showed moderate
      cytotoxic activity. However, compound 1 did not show appreciable antifungal
      activity against wild type C. albicans, Cryptococcus neoformans, Aspergillus
      niger, Penicillium sp., Rhizopus sporangia or Sordaria sp. 

PMID- 22963322
TI  - Self-assembled monolayer exchange reactions as a tool for channel interface
      engineering in low-voltage organic thin-film transistors.
AB  - In this work, we compared the kinetics of monolayer self-assembly long-chained
      carboxylic acids and phosphonic acids on thin aluminum oxide surfaces and
      investigated their dielectric properties in capacitors and low-voltage organic
      thin-film transistors. Phosphonic acid anchor groups tend to substitute
      carboxylic acid molecules on aluminum oxide surfaces and thus allow the formation
      of mixed or fully exchanged monolayers. With different alkyl chain substituents
      (n-alkyl or fluorinated alkyl chains), the exchange reaction can be monitored as
      a function of time by static contact angle measurements. The threshold voltage in
      alpha,alpha'-dihexyl-sexithiophene thin-film transistors composed of such mixed
      layer dielectrics correlates with the exchange progress and can be tuned from
      negative to positive values or vice versa depending on the dipole moment of the
      alkyl chain substituents. The change in the dipole moment with increasing
      exchange time also shifts the capacitance of these devices. The rate constants
      for exchange reactions determined by the time-dependent shift of static contact
      angle, threshold voltage, and capacitance exhibit virtually the same value thus
      proving the exchange kinetics to be highly controllable. In general, the exchange
      approach is a powerful tool in interface engineering, displaying a great
      potential for tailoring of device characteristics.

PMID- 22963321
TI  - Shear-dependent adhesion of leukocytes and lectins to the endothelium and
      concurrent changes in thickness of the glycocalyx of post-capillary venules in
      the low-flow state.
AB  - OBJECTIVE: To elucidate shear-dependent effects of deformation of the endothelial
      glycocalyx on adhesion of circulating ligands in post-capillary venules, and
      delineate effect of MMPs. METHODS: Adhesion of WBCs and lectin-coated FLMs (0.1
      MUm diameter) to EC of post-capillary venules in mesentery was examined during
      acute reductions in shear rates (gamma., hemorrhagic hypotension). Adhesion was
      examined with or without superfusion with 0.5 MUm doxycycline to inhibit MMPs.
      Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa
      dextran from the EC surface. RESULTS: During superfusion with Ringers, rapid
      reductions in gamma. resulted in a significant rise in WBC adhesion and a twofold
      rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion
      increased twofold under high- and low-flow conditions. FLM adhesion was invariant
      with gamma. throughout the network in the normal (high)-flow state. With
      reductions in gamma., thickness of the glycocalyx increased significantly, with
      or without doxycycline. CONCLUSIONS: The concurrent increase in WBC and FLM
      adhesion with increased thickness of the glycocalyx during reductions in shear
      suggests that glycocalyx core proteins recoil from their deformed steady-state
      configuration, which increases exposure of binding sites for circulating ligands.

PMID- 22963324
TI  - Dietary restriction: critical co-factors to separate health span from life span
      benefits.
AB  - Dietary restriction (DR), typically a 20%-40% reduction in ad libitum or "normal"
      nutritional energy intake, has been reported to extend life span in diverse
      organisms, including yeast, nematodes, spiders, fruit flies, mice, rats, and
      rhesus monkeys. The magnitude of the life span enhancement appears to diminish
      with increasing organismal complexity. However, the extent of life span extension
      has been notoriously inconsistent, especially in mammals. Recently, Mattison et
      al. reported that DR does not extend life span in rhesus monkeys in contrast to
      earlier work of Colman et al. Examination of these papers identifies multiple
      potential confounding factors. Among these are the varied genetic backgrounds and
      composition of the "normal" and DR diets. In monkeys, the correlation of DR with
      increased health span is stronger than that seen with life span and indeed may be
      separable. Recent mechanistic studies in Drosophila implicate non-genetic co
      factors such as level of physical activity and muscular fatty acid metabolism in
      the benefits of DR. These results should be followed up in mammals. Perhaps
      levels of physical activity among the cohorts of rhesus monkeys contribute to
      inconsistent DR effects. To understand the maximum potential benefits from DR
      requires differentiating fundamental effects on aging at the cellular and
      molecular levels from suppression of age-associated diseases, such as cancer. To
      that end, it is important that investigators carefully evaluate the effects of DR
      on biomarkers of molecular aging, such as mutation rate and epigenomic
      alterations. Several short-term studies show that humans may benefit from DR in
      as little as 6 months, by achieving lowered fasting insulin levels and improved
      cardiovascular health. Optimized health span engineering will require a much
      deeper understanding of DR.

PMID- 22963323
TI  - High depth, whole-genome sequencing of cholera isolates from Haiti and the
      Dominican Republic.
AB  - BACKGROUND: Whole-genome sequencing is an important tool for understanding
      microbial evolution and identifying the emergence of functionally important
      variants over the course of epidemics. In October 2010, a severe cholera epidemic
      began in Haiti, with additional cases identified in the neighboring Dominican
      Republic. We used whole-genome approaches to sequence four Vibrio cholerae
      isolates from Haiti and the Dominican Republic and three additional V. cholerae
      isolates to a high depth of coverage (>2000x); four of the seven isolates were
      previously sequenced. RESULTS: Using these sequence data, we examined the effect
      of depth of coverage and sequencing platform on genome assembly and
      identification of sequence variants. We found that 50x coverage is sufficient to
      construct a whole-genome assembly and to accurately call most variants from 100
      base pair paired-end sequencing reads. Phylogenetic analysis between the newly
      sequenced and thirty-three previously sequenced V. cholerae isolates indicates
      that the Haitian and Dominican Republic isolates are closest to strains from
      South Asia. The Haitian and Dominican Republic isolates form a tight cluster,
      with only four variants unique to individual isolates. These variants are located
      in the CTX region, the SXT region, and the core genome. Of the 126 mutations
      identified that separate the Haiti-Dominican Republic cluster from the V.
      cholerae reference strain (N16961), 73 are non-synonymous changes, and a number
      of these changes cluster in specific genes and pathways. CONCLUSIONS: Sequence
      variant analyses of V. cholerae isolates, including multiple isolates from the
      Haitian outbreak, identify coverage-specific and technology-specific effects on
      variant detection, and provide insight into genomic change and functional
      evolution during an epidemic.

PMID- 22963326
TI  - Effects of prior short multiple-sprint exercises with different intersprint
      recoveries on the slow component of oxygen uptake during high-intensity exercise.
AB  - This study compares the effects of two short multiple-sprint exercise (MSE) (6 *
      6 s) sessions with two different recovery durations (30 s or 180 s) on the slow
      component of oxygen uptake ([Formula: see text]O(2)) during subsequent high
      intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of
      the difference between the gas exchange threshold and [Formula: see text]O(2peak)
      (Delta50). Then, the subjects performed two MSEs of 6 * 6 s separated by two
      intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min
      later by the Delta50 (Delta50(30) and Delta50(180), respectively).
      Electromyography (EMG) activities of the vastus medialis and lateralis were
      measured throughout each exercise bout. During MSE(30), muscle activity (root
      mean square) increased significantly (p <= 0.04), with a significant leftward
      shifted median frequency of the power density spectrum (MDF; p <= 0.01), whereas
      MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean
      [Formula: see text]O(2) value was significantly higher in MSE(30) than in
      MSE(180) (p < 0.001). During Delta50(30), [Formula: see text]O(2) and the
      deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%,
      p = 0.02, and -34%, p = 0.003, respectively) compared with Delta50. There were no
      significant modifications of the [Formula: see text]O(2) slow component in
      Delta50(180) compared with Delta50 (p = 0.32). The neuromuscular and metabolic
      adaptations during MSE(30) (preferential activation of type I muscle fibers
      evidenced by decreased MDF and a greater aerobic metabolism contribution to the
      required energy demands), but not during MSE(180), may lead to reduced [Formula:
      see text]O(2) and [HHb] slow components, suggesting an alteration in motor units
      recruitment profile (i.e., change in the type of muscle fibers recruited) and
      (or) an improved muscle O(2) delivery during subsequent exercise.

PMID- 22963327
TI  - Cord blood chemerin and obestatin levels in large for gestational age infants.
AB  - OBJECTIVE: To investigate possible alterations in cord blood levels of
      adipokines, chemerin and obestatin (secreted by adipose tissue and associated
      with later development of insulin resistance/metabolic syndrome), as well as
      insulin, in large for gestational age (LGA) and appropriate for gestational age
      (AGA) pregnancies, granted that these groups differ in body fat mass and
      metabolic/endocrine mechanisms. METHODS: Cord blood chemerin, obestatin, and
      insulin concentrations were prospectively measured in 40 LGA (9 born from
      diabetic and 31 from nondiabetic mothers) and 40 AGA singleton full-term infants.
      RESULTS: Cord blood chemerin concentrations were significantly higher in LGA
      compared with AGA neonates (b = 38.91, SE 9.29, p < 0.001). In contrast, no
      significant differences in obestatin concentrations were observed between groups.
      Insulin levels were significantly elevated as customized centiles increased (b =
      0.003, SE = 0.001, p = 0.032). CONCLUSIONS: Higher chemerin concentrations in LGA
      neonates possibly reflect the increased adipose tissue in this group. Lack of
      difference between the two groups in circulating levels of obestatin-possibly a
      sensitive marker of insulin resistance-might be due to development of metabolic
      disorders later in life.

PMID- 22963329
TI  - Detecting the association between residual thrombus and post-thrombotic
      classification of chronic venous disease with range regression.
AB  - This paper addresses a clinical hypothesis detected by the method of range
      regression, a new statistical method portraying the clinical response via the
      range of an explanatory variable. For patients with iliofemoral deep venous
      thrombosis, it has long been clinically suspected that residual thrombus affects
      the quality of life after catheter-directed thrombolysis. However, such important
      medical experience has not been validated or scientifically quantified by
      experimental or observational data. In clinical practice, this association may
      directly affect the duration of thrombolytic therapy or other attempts at clot
      removal. In this study, we develop a new regression model to identify how the
      quantity of clot lysed affects the clarification of chronic venous disease after
      catheter-directed thrombolysis (a correlated index on postthrombotic quality of
      life). Bridging clinical insight with statistics by means of medical records of
      62 IFDVT patients, the new method reveals that residual thrombus significantly
      and substantially affects post-thrombotic clarification of chronic venous
      disease. The conclusion of the new method is confirmed by a conventional logistic
      regression method when 50% thrombus removal is treated as a categorization
      threshold. This new approach is applicable to analyze other clinical or medical
      variables on the treatment of venous diseases.

PMID- 22963328
TI  - Effects of a 6-month multimodal training intervention on retention of functional
      fitness in older adults: a randomized-controlled cross-over design.
AB  - BACKGROUND: Older adults have the highest rates of disability, functional
      dependence and use of healthcare resources. Training interventions for older
      individuals are of special interest where regular physical activity (PA) has many
      health benefits. The main purpose of this study was to assess the immediate and
      long-term effects of a 6-month multimodal training intervention (MTI) on
      functional fitness in old adults. METHODS: For this study, 117 participants, 71
      to 90 years old, were randomized in immediate intervention group and a control
      group (delayed intervention group). The intervention consisted of daily endurance
      and twice-a-week strength training. The method was based on a randomized
      controlled cross-over design. Short Physical Performance Battery (SPPB), 8 foot
      up-and-go test, strength performance, six min walking test (6 MW), physical
      activity, BMI and quality of life were obtained at baseline, after a 6-month
      intervention- and control phase, again after 6-month crossover- and delayed
      intervention phase, and after anadditional 6-month follow-up. RESULTS: After 6
      months of MTI, the intervention group improved in physical performance compared
      with the control group via Short Physical Performance Battery (SPPB) score (mean
      diff = 0.6, 95 % CI: 0.1, 1.0) and 8-foot up-and-go test (mean diff = -1.0 s, 95
      % CI: -1.5, -0.6), and in endurance performance via 6-minute walking test (6 MW)
      (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2). In strength performance via knee
      extension the intervention group improved while control group declined (mean diff
      = 55.0 Newton, 95 % CI: 28.4, 81.7), and also in PA (mean diff = 125.9 cpm, 95 %
      CI: 96.0, 155.8). Long-term effects of MTI on the particpants was assesed by
      estimating the mean difference in the variables measured between time-point 1 and
      4: SPPB (1.1 points, 95 % CI: 0.8, 1.4); 8-foot up-and-go (-0.9 s, 95 % CI: -1.2,
      -0.6); 6 MW (18.7 m, 95 % CI: 6.5, 31.0); knee extension (4.2 Newton, 95 % CI: 
      10.0, 18.3); hand grip (6.7 Newton, 95 % CI: -4.4, 17.8); PA (-4.0 cpm, 95 % CI: 
      33.9, 26.0); BMI (-0.6 kg/m2, 95 % CI: -0.9, -0.3) and Icelandic quality of life
      (0.3 points, 95 % CI: -0.7, 1.4). CONCLUSIONS: Our results suggest that regular
      MTI can improve and prevent decline in functional fitness in older individuals,
      influence their lifestyle and positively affect their ability to stay
      independent, thus reducing the need for institutional care. TRIAL REGISTRATION:
      This study was approved by the National Bioethics Committee in Iceland,
      VSNb20080300114/03-1.

PMID- 22963330
TI  - Evaluation of a Japanese "Prevention of long-term care" project for the
      improvement in oral function in the high-risk elderly.
AB  - AIM: The purpose of this study was to analyze the improvement in oral function
      and environment in high-risk elderly persons participating in a program to
      improve oral function organized by their local government. METHODS: Participants
      comprised 36 high-risk elderly and the mean age was 77.11 +/- 7.24 years. The
      program involved training sessions carried out five or six times every 2-3 weeks
      for 3 months. Oral function and environment was evaluated before and after the
      program. The research period extended from 2008 to 2010. RESULTS: The effects of
      intervention were clearly observed in oral diadochokinesis score in the high-risk
      elderly. Persons with a lower repetitive saliva swallowing test (RSST) and oral
      diadochokinesis score before intervention showed a tendency toward even greater
      improvement. No significant changes were observed in saliva secretion or total
      amounts of Streptococcus mutans, Lactobacilli, Candida or total microorganisms.
      CONCLUSIONS: The effects of intervention were clearly recognized in regards to
      oral diadochokinesis. Improvement in RSST and oral diadochokinesis scores was
      marked in those persons showing a lower number of articulations before
      intervention.

PMID- 22963332
TI  - Synthesis and characterization of hypoelectronic tantalaboranes: comparison of
      the geometric and electronic structures of [(Cp*TaX)2B5H11] (X = Cl, Br, and I).
AB  - Mild thermolysis of tantalaborane [(Cp*Ta)(2)B(5)H(11)], 1 (Cp* = eta(5)
      C(5)Me(5)) in presence of halogen sources affords the open cage clusters
      [(Cp*TaX)(2)B(5)H(11)], 2-4 (2: X = Cl; 3: X = Br; and 4: X = I) in good yields.
      In contrast, the tetraborohydride cluster, [(Cp*Ta)(2)B(4)H(9)(MU-BH(4))], 5,
      under the same reaction conditions forms the B-H substituted cluster
      [(Cp*Ta)(2)B(4)H(8)I(MU-BH(4))], 6. All the new metallaboranes have been
      characterized by mass spectrometry, (1)H, (11)B, (13)C NMR spectroscopy, and
      elemental analysis, and the structural types were established by crystallographic
      analysis of clusters 3, 4, and 6. Density functional theory (DFT) calculations at
      the BP86/TZ2P ZORA level reveal geometries in agreement with the structure
      determinations, large gaps between the highest occupied molecular orbital (HOMO)
      and the lowest unoccupied molecular orbital (LUMO) in accord with their
      stabilities. B3LYP-computed (11)B chemical shifts accurately reflect the
      experimentally measured shifts. Clusters 2-4 can be viewed as 7-sep 7-vertex
      oblatoarachno M(2)B(5) clusters which can be generated from a 7-sep 9-vertex
      oblatocloso M(2)B(7) cluster by removal of two equatorial boron atoms. Cluster 6
      can be considered as an electron-deficient 6-sep 6-vertex oblatoarachno M(2)B(4)
      cluster derived from an 8-vertex oblatocloso hexagonal bipyramidal cluster, in
      which BH(4)(-) anion is weakly bonded in a bidentate mode.

PMID- 22963331
TI  - Individual differences in the effects of mood on sexuality: the revised Mood and
      Sexuality Questionnaire (MSQ-R).
AB  - Previous research using the Mood and Sexuality Questionnaire (MSQ) has revealed
      substantial variability in how negative mood impacts sexual response and
      behavior. However, the MSQ does not address differences between desire for solo
      or partnered sexual activity, examine the effects of sexual activity on mood, or
      assess the effects of positive mood. This article presents the development and
      factor structure of the Revised Mood and Sexuality Questionnaire (MSQ-R). An
      exploratory factor analysis in a sample of heterosexual men, homosexual men, and
      heterosexual women (N = 1,983) produced eight factors. Considerable variability
      was found in how moods influence sexual desire and arousal, in the effects of
      mood on sexual behavior, and in the reciprocal effects of sexual activity on
      mood. Among other findings, heterosexual women were less likely than heterosexual
      men and homosexual men to experience increased sexual desire and arousal when
      anxious or stressed, whereas homosexual men and heterosexual women were less
      likely than heterosexual men to experience increased desire when sad or
      depressed. Heterosexual men and heterosexual women were more likely than
      homosexual men to report increased desire when in a positive mood.
      Intercorrelations and correlations with various sexual behaviors varied by group.
      Limitations and implications of the findings are discussed.

PMID- 22963333
TI  - Altered response to hydrogen sulphide during experimental colitis in rats.
AB  - Hydrogen sulphide (H2 S) is produced in the intestine by sulphate-reducing
      bacteria and during metabolism of L-cysteine within the mucosa. This
      gasotransmitter induces anion secretion by stimulating enteric neurons and by a
      direct effect on epithelial cells. As H2 S is discussed to exert both pro- and
      anti-inflammatory actions, we aimed to investigate the role of H2 S during
      experimental colitis by comparing the effects of blockade of H2 S-forming
      endogenous enzymes with the effect of a S-reduced diet to diminish microbial
      production of H2 S. Rectal application of trinitrobenzenesulfonic acid (TNBS) was
      used to induce chronic colitis. The level of inflammation was assessed
      macroscopically and histologically. In Ussing chamber experiments, colonic
      specimens from TNBS-treated animals exhibited a higher tissue conductance, that
      is, a higher epithelial permeability, and a slightly reduced basal short-circuit
      current (a measure of net ion transport) in relation to non-inflamed control
      tissue. Analgetic treatment with flupirtine, a central antinociceptive analgetic,
      did not interfere with the induction of the inflammatory response so that all
      animals were treated with flupirtine to reduce pain and distress during the
      development of colitis. The secretory response evoked by an exogenous H2 S donor,
      NaHS, was significantly decreased after induction of colitis, whereas the
      response to Ca(2+) - or cAMP-dependent secretagogues was unaltered. This
      downregulation was not observed in the colitis group fed on a S-reduced diet. The
      decreased NaHS response indicates a desensitization of the tissue by
      inflammation, which might be explained by an upregulation of colonic H2 S
      production as described in some models of inflammation. 

PMID- 22963334
TI  - Experimental identification and theoretical analysis of a thermally stabilized
      green fluorescent protein variant.
AB  - In this study, we aim to relate experimentally measured macroscopic properties to
      dynamic and structural changes as calculated by molecular dynamics (MD)
      simulations. We performed the analysis on four GFP (green fluorescent protein)
      variants, which have amino acid replacements or insertion in a flexible region on
      the protein surface and which resulted from a previous protein splicing reaction
      optimization experiment. The variants are a reference GFP (CEGFP), GFP-N144C, GFP
      N144C/Y145F, and a GFP with five residues inserted between Y145 and N146 (GFP
      5ins). As a result, we identified a single Y145F mutation that increased the
      thermal stability of GFP-N144C/Y145F by 3-4  degrees C. Because circular
      dichroism measurements indicated that the overall GFP beta-barrel fold was
      maintained in all variants, we presumed that the fluorescence activity and
      thermal stability related to local changes that could be detected by standard MD
      simulations. The 60 ns MD simulations indicated that the Y145's hydroxyl group,
      which is straight and buried in the crystal structure, was bent avoiding the
      hydrophobic core during the simulation in both CEGFP and GFP-N144C. This local
      strain was relieved in GFP-N144C/Y145F, where the tyrosine's hydroxyl group was
      replaced with the F145 hydrophobic aliphatic carbon. F145 remained indeed buried
      during the simulation maintaining local compactness, which presumably reflected
      the improved thermal stability of GFP-N144C/Y145F. Furthermore, the analysis of
      internal water molecules localized within the GFP's beta-barrel suggested that a
      change in the local hydrogen bonding pattern around the chromophore correlated
      with a strong fluorescence activity decrease in GFP-5ins. Although relating
      experimental observation with calculated molecular features proved to be
      delicate, this study suggested that some microscopic features could be useful
      reporters for redesigning GFPs and other proteins. The newly identified GFP
      N144C/Y145F was among the most stable GFP variant and demonstrates the potential
      of such computer-aided design.

PMID- 22963336
TI  - Pentafluorophenylammonium triflate (PFPAT): an efficient, practical, and cost
      effective catalyst for one-pot condensation of beta-naphthol, aldehydes and
      cyclic 1,3-dicarbonyl compounds.
AB  - A pentafluorophenylammonium triflate (PFPAT) catalyst (10 mol%) efficiently
      promoted one-pot condensation of beta-naphthol, aldehydes, and cyclic 1,3
      dicarbonyl compounds in good to excellent yield under mild reaction conditions.
      These catalytic condensations have advantages from the viewpoint of green
      chemistry. PFPAT organocatalyst is air-stable, cost-effective, easy to handle,
      and easily removed from the reaction mixtures.

PMID- 22963337
TI  - Fitness on facebook: advertisements generated in response to profile content.
AB  - Obesity is a challenging problem affecting almost half of college students. To
      solve this complex health problem, innovative approaches must be utilized. Over
      94 percent of college students maintain a Facebook profile, providing them a
      venue to publicly disclose current fitness behaviors. Displayed advertisements on
      Facebook are tailored to profile content and may influence college students'
      fitness efforts. Facebook may be an innovative venue for improving college
      students' fitness behaviors. The purpose of this project was to determine (a) how
      and to what extent college students are discussing fitness on Facebook, and (b)
      how user-generated fitness information is linked to advertisements for fitness
      products and advice. First, public Facebook profiles of individual college
      students were evaluated for displayed fitness references based on 10 fitness
      behavior categories. Inter-rator reliability between two coders was 91.18
      percent. Second, 10 fitness status updates were generated and posted by a
      researcher on a Facebook profile; the first 40 linked advertisements to these
      statements were examined. Advertisements were categorized and then examined for
      relevance to the college population. A total of 57 individual profiles were
      examined; owners had an average age of 18.3 years (SD=0.51), and 36.8 percent
      were women. About 71.9 percent of profiles referenced one or more fitness
      behavior; 97.6 percent referenced exercise, 4.9 percent dieting, and 4.9 percent
      unhealthy eating. Among the first 40 ads linked to generated status updates, 40.3
      percent were fitness related. Most advertisements were for charity runs (30.4
      percent), fitness apparel (24.2 percent), or fad diets (9.9 percent). Students
      referred both healthy and unhealthy fitness behaviors on their Facebook profiles,
      and these trigger the display of fitness-related advertisements of which few
      appear applicable. A community- or university-based intervention could be
      designed and implemented to provide relevant and tailored information to students
      on Facebook.

PMID- 22963335
TI  - Novel and unexpected bacterial diversity in an arsenic-rich ecosystem revealed by
      culture-dependent approaches.
AB  - BACKGROUND: Acid Mine Drainages (AMDs) are extreme environments characterized by
      very acid conditions and heavy metal contaminations. In these ecosystems, the
      bacterial diversity is considered to be low. Previous culture-independent
      approaches performed in the AMD of Carnoules (France) confirmed this low species
      richness. However, very little is known about the cultured bacteria in this
      ecosystem. The aims of the study were firstly to apply novel culture methods in
      order to access to the largest cultured bacterial diversity, and secondly to
      better define the robustness of the community for 3 important functions: As(III)
      oxidation, cellulose degradation and cobalamine biosynthesis. RESULTS: Despite
      the oligotrophic and acidic conditions found in AMDs, the newly designed media
      covered a large range of nutrient concentrations and a pH range from 3.5 to 9.8,
      in order to target also non-acidophilic bacteria. These approaches generated 49
      isolates representing 19 genera belonging to 4 different phyla. Importantly,
      overall diversity gained 16 extra genera never detected in Carnoules. Among the
      19 genera, 3 were previously uncultured, one of them being novel in databases.
      This strategy increased the overall diversity in the Carnoules sediment by 70%
      when compared with previous culture-independent approaches, as specific
      phylogenetic groups (e.g. the subclass Actinobacteridae or the order Rhizobiales)
      were only detected by culture. Cobalamin auxotrophy, cellulose degradation and
      As(III)-oxidation are 3 crucial functions in this ecosystem, and a previous meta-
      and proteo-genomic work attributed each function to only one taxon. Here, we
      demonstrate that other members of this community can also assume these functions,
      thus increasing the overall community robustness. CONCLUSIONS: This work
      highlights that bacterial diversity in AMDs is much higher than previously
      envisaged, thus pointing out that the AMD system is functionally more robust than
      expected. The isolated bacteria may be part of the rare biosphere which remained
      previously undetected due to molecular biases. No matter their current ecological
      relevance, the exploration of the full diversity remains crucial to decipher the
      function and dynamic of any community. This work also underlines the importance
      to associate culture-dependent and -independent approaches to gain an integrative
      view of the community function.

PMID- 22963338
TI  - Application of ozone therapy in the vestibulocochlear syndrome.
AB  - The aim of this study was to evaluate the efficacy of ozone therapy in the
      treatment of 50 patients with peripheral vestibulocochlear syndrome. Ozone was
      injected in the cervical region C2-C3, for 20 sessions. Evaluation criteria was
      based in the evolution of nystagmus, tinnitus, hearing loss and vertigo. Also,
      oxidative stress parameters were measured. Results demonstrated that patient
      improvements, according to vertigo, hearing loss, tinnitus and nystagmus, were of
      90, 80, 65 and 100%, respectively. These patients were initially under condition
      of systemic oxidative stress, however, at the end of the study a redox balance
      was achieved. No side effects were observed.

PMID- 22963339
TI  - Heterogeneous uptake of amines by citric acid and humic acid.
AB  - Heterogeneous uptake of methylamine (MA), dimethylamine (DMA), and trimethylamine
      (TMA) onto citric acid and humic acid was investigated using a Knudsen cell
      reactor coupled to a quadrupole mass spectrometer at 298 K. Acid-base reactions
      between amines and carboxylic acids were confirmed. The observed uptake
      coefficients of MA, DMA, and TMA on citric acid at 298 K were measured to be 7.31
      +/- 1.13 * 10(-3), 6.65 +/- 0.49 * 10(-3), and 5.82 +/- 0.68 * 10(-3),
      respectively, and showed independence of sample mass. The observed uptake
      coefficients of MA, DMA, and TMA on humic acid at 298 K increased linearly with
      sample mass, and the true uptake coefficients of MA, DMA, and TMA were measured
      to be 1.26 +/- 0.07 * 10(-5), 7.33 +/- 0.40 * 10(-6), and 4.75 +/- 0.15 * 10(-6),
      respectively. Citric acid, having stronger acidity, showed a higher reactivity
      than humic acid for a given amine; while the steric effect of amines was found to
      govern the reactivity between amines and citric acid or humic acid.

PMID- 22963341
TI  - Increased neonatal morbidity despite pulmonary maturity for deliveries occurring
      before 39 weeks.
AB  - OBJECTIVE: To compare neonatal outcomes following deliveries <39 weeks after
      confirmation of fetal lung maturity with scheduled deliveries >=39 weeks.
      METHODS: A retrospective cohort study examining neonatal outcomes of women who
      were delivered following documented fetal pulmonary maturity at 36, 37, and 38
      weeks compared to women undergoing a scheduled delivery at 39, 40, and 41 weeks.
      The chi(2)-test and Student's t-test were used to compare categorical and
      continuous data, respectively. RESULTS: Delivery prior to 39 weeks following
      fetal pulmonary maturity was associated with a 8.4% composite neonatal morbidity
      rate as compared to 3.3% for deliveries at 39 weeks or greater (relative risk
      [RR] 2.9; confidence interval [CI] 2.4-3.6). Neonatal respiratory morbidity was
      significantly higher (5.4%) for those delivering at less than 39 weeks with
      documented fetal pulmonary maturity as compared to 2.1% for those delivering at
      39 weeks or greater (RR 3.0; CI 2.3-3.9). Increased neonatal morbidity persisted
      for those delivered prior to 39 weeks even after excluding all diabetics (p <
      0.001). Significant increases in neonatal morbidity were noted for deliveries
      prior to 39 weeks regardless of the mode of delivery. CONCLUSION: Despite fetal
      pulmonary maturity, delivery before 39 weeks is associated with significantly
      increased neonatal morbidity when compared to scheduled deliveries at 39 weeks or
      greater.

PMID- 22963340
TI  - Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma
      production and bioinformatics prediction.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious
      disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS
      CoV spike protein are well known, but no systematic evaluation of the functional
      and structural roles of each residue has been reported for these antigenic
      epitopes. Analysis of the functional importance of side-chains by mutational
      study may exaggerate the effect by imposing a structural disturbance or an
      unusual steric, electrostatic or hydrophobic interaction. RESULTS: We
      demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S
      DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover,
      S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN,
      SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of
      S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine
      (A), lysine (K) or aspartic acid (D), respectively. ANN was used to estimate the
      binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were
      predicated to possess the most important role in peptide binding. Additionally,
      these one residue mutated peptides were synthesized, and IFN-gamma production
      induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased
      obviously. CONCLUSIONS: We demonstrated that S366-374 is an optimal H-2 Kd CTL
      epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in
      the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact
      with TCR on the surface of CD8-T cells.

PMID- 22963342
TI  - Synthesis, structure, and physical properties of Ln(Cu,Al,Ga)(13-x) (Ln = La-Pr,
      and Eu) and Eu(Cu,Al)(13-x).
AB  - Ln(Cu,Al,Ga)(13-x) (Ln = La-Pr, and Eu; x ~ 0.2) were synthesized by a combined
      Al/Ga flux. Single crystal X-ray and neutron diffraction experiments revealed
      that these compounds crystallize in the NaZn(13) structure-type (space group
      Fm3[overline]c) with lattice parameters of a ~ 12 A, V ~ 1600 A, and Z ~ 8. Our
      final neutron models led us to conclude that Cu is occupationally disordered on
      the 8b Wyckoff site while Cu, Al, and Ga are substitutionally disordered on the
      96i Wyckoff site of this well-known structure-type. The magnetic susceptibility
      data show that Ce(Cu,Al,Ga)(13-x) and Pr(Cu,Al,Ga)(13-x) exhibit paramagnetic
      behavior down to the lowest temperatures measured while Eu(Cu,Al,Ga)(13-x)
      displays ferromagnetic behavior below 6 K. Eu(Cu,Al)(13-x) was prepared via arc
      melting and orders ferromagnetically below 8 K. The magnetocaloric properties of
      Eu(Cu,Al,Ga)(13-x) and Eu(Cu,Al)(13-x) were measured and compared. Additionally,
      an enhanced value of the Sommerfeld coefficient (gamma = 356 mJ/mol-K(2)) was
      determined for Pr(Cu,Al,Ga)(13-x). Herein, we present the synthesis, structural
      refinement details, and physical properties of Ln(Cu,Al,Ga)(13-x) (Ln = La-Pr,
      and Eu) and Eu(Cu,Al)(13-x).

PMID- 22963343
TI  - Antioxidant activity of methanol extract of Helichrysum foetidum Moench.
AB  - Methanol extract of Helichrysum foetidum Moench (Asteraceae) was investigated for
      antioxidative properties. The antioxidant activities were investigated by 2,2'
      azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical-scavenging, beta-carotene/linoleic acid assay,
      scavenging of hydrogen peroxide (HRPO test), superoxide anion scavenging (S.A.S.
      test) and hypochlorous acid scavenging (taurine test). The antioxidant activity
      was reported as IC50 and reveals Trolox-like antioxidative effects. 

PMID- 22963344
TI  - The impairment of endocardial radial strain is related to aortic stenosis
      severity in patients with aortic stenosis and preserved LV ejection fraction
      using two-dimensional speckle tracking echocardiography.
AB  - BACKGROUND: Myocardial function is heterogeneous in different myocardial layers.
      Recently, two-dimensional speckle tracking echocardiography has been used to
      define myocardial deformation parameters of the left ventricular (LV) segment.
      This study aimed to investigate strain in subendocardial and subepicardial layers
      in patients with aortic stenosis (AS) and preserved LV ejection fraction (LVEF)
      using speckle tracking echocardiography. METHODS: Parasternal short-axis and
      apical long-axis views of the left ventricle were acquired at the mid-papillary
      level in 35 control subjects and 32 patients with AS and preserved LVEF. Radial,
      circumferential, and longitudinal strain in subendocardial and subepicardial
      layers at the posterior and anteroseptal segments were calculated. RESULTS: There
      was no significant difference in circumferential strain in subendocardial and
      subepicardial layers between the control subjects and the patients with AS.
      Similarly, there was no significant difference in epicardial radial strain at the
      posterior and anteroseptal segments between the control subjects and the patients
      with AS. Longitudinal strain at both the posterior and anteroseptal segments was
      significantly decreased in the AS group compared with that in the control group.
      AS patients had significantly decreased values of endocardial radial strain
      compared with those in controls (anteroseptal: 18.2 +/- 11.2 vs. 34.5 +/- 14.8, P
      < 0.005; posterior: 25.2 +/- 14.8 vs. 32.6 +/- 12.6, P < 0.05). In the AS group,
      endocardial radial strain in the posterior and anteroseptal segments was
      significantly correlated with the aortic valve area (posterior: r = 0.41, P <
      0.05; anteroseptal: r = 0.33, P < 0.05). CONCLUSION: Patients with AS and
      preserved LVEF have impaired longitudinal strain and endocardial radial strain,
      although circumferential strain and epicardial radial strain are preserved.
      Despite preserved LVEF, endocardial radial strain was associated with AS
      severity.

PMID- 22963345
TI  - Trait self-esteem and claimed self-handicapping motives in sports situations.
AB  - We examined the relationship between physical self-esteem and claimed self
      handicapping among athletes by taking motives into consideration. In Study 1, 99
      athletes were asked to report their tendency to engage in claimed self
      handicapping for self-protective and self-enhancement motives (trait measures).
      Low self-esteem athletes reported a higher tendency to engage in claimed self
      handicapping for these two motives compared with high self-esteem athletes.
      Neither low nor high self-esteem athletes reported a preference for one motive
      over the other. In Study 2, 107 athletes participated in a test that was
      ostensibly designed to assess high physical abilities - and thus to encourage
      self-handicapping for self-enhancement motives (success-meaningful condition) -
      or to assess low physical abilities, and thus to encourage self-handicapping for
      self-protective motives (failure-meaningful condition). Before starting the test,
      athletes were given the opportunity to claim handicaps that could impair their
      performance. Low self-esteem athletes claimed more handicaps than high self
      esteem athletes in both conditions. Findings suggest that low physical self
      esteem athletes engage more in claimed handicapping regardless of motives,
      relative to high physical self-esteem athletes.

PMID- 22963346
TI  - Gender disparities in the association between epicardial adipose tissue volume
      and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging
      study in Japanese subjects.
AB  - BACKGROUND: Growing evidence suggests that epicardial adipose tissue (EAT) may
      contribute to the development of coronary artery disease (CAD). In this study, we
      explored gender disparities in EAT volume (EATV) and its impact on coronary
      atherosclerosis. METHODS: The study population consisted of 90 consecutive
      subjects (age: 63 +/- 12 years; men: 47, women: 43) who underwent 256-slice multi
      detector computed tomography (MDCT) coronary angiography. EATV was measured as
      the sum of cross-sectional epicardial fat area on CT images, from the lower
      surface of the left pulmonary artery origin to the apex. Subjects were segregated
      into the CAD group (coronary luminal narrowing > 50%) and non-CAD group. RESULTS:
      EATV/body surface area (BSA) was higher among men in the CAD group than in the
      non-CAD group (62 +/- 13 vs. 33 +/- 10 cm3/m2, p < 0.0001), but did not differ
      significantly among women in the 2 groups (49 +/- 18 vs. 42 +/- 9 cm3/m2, not
      significant). Multivariate logistic analysis showed that EATV/BSA was the single
      predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors
      excluded were age, body mass index, hypertension, diabetes mellitus, and
      hyperlipidemia. CONCLUSIONS: Increased EATV is strongly associated with coronary
      atherosclerosis in men.

PMID- 22963347
TI  - Time to follow up after an abnormal finding in organized gastric cancer screening
      in Korea.
AB  - BACKGROUND: The prognosis for an abnormal medical finding is affected by both
      early detection and adherence to the presecribed schedule for follow-up
      examinations. In this study, we examined the time to follow up after an abnormal
      finding and determined the risk factors related to delays in follow up in a
      population-based screening program. METHODS: The study population consisted of
      patients who were newly diagnosed with gastric cancer through a gastric cancer
      screening program sponsored by the National Cancer Screening Program (NCSP) in
      2005. Due to the skewed nature of the distribution of time to follow up, medians
      and interquartile ranges (IQR) are presented, and we analyzed the number of days
      preceding the follow-up time as a binary variable (<= 90 days or >90 days). We
      used logistic regression analyses to evaluate the risk factors for a long delay.
      RESULTS: The median number of days to follow-up initiation after an abnormal
      finding was 11 (IQR 7-27); 13.9% of the patients with gastric cancer obtained
      their follow-up evaluation more than 90 days. Age, type of health insurance,
      screening method, and screening results were risk factors for delays in follow
      up. CONCLUSIONS: This study examined delays from the time of the discovery of an
      abnormal finding to time of the follow-up evaluation. Because inadequate follow
      up of abnormal exam results undermines the potential benefits of cancer
      screening, it is important to organize services that minimize delays between
      cancer screening and treatment.

PMID- 22963348
TI  - Posterior chamber injection of intracameral mydriatics increases the durability
      of the mydriatic response.
AB  - PURPOSE: To compare the mydriatic effect of intracameral mydriatics injected into
      the anterior or the posterior chamber in routine phacoemulsification cataract
      surgery. METHODS: Forty-four patients planned for unilateral phacoemulsification
      surgery were included after informed consent. Mydriasis was achieved by injecting
      150 MUl of a mixture of phenylephrine 1.5% and lidocaine 1.0% at the beginning of
      the procedure. The patients were randomly assigned to injection into the anterior
      or the posterior chamber. The pupils were filmed during the procedures, and the
      mean pupil diameters were measured at predetermined intervals from the video
      recordings by an independent observer. RESULTS: Immediately after the injection,
      the pupils were larger after posterior chamber injection (3.8 +/- 0.8 versus 3.1
      +/- 0.7 mm; p = 0.004). A similar difference was seen after the
      phacoemulsification (6.4 +/- 0.7 versus 5.9 +/- 1.0 mm; p = 0.031). The mydriatic
      durability was also better after posterior injection (p = 0.004-0.041).
      CONCLUSIONS: Apart from immediately after the injection, the initial mydriatic
      response was similar with both injection techniques, but the durability of the
      mydriasis was slightly better after a posterior chamber injection of ICM.

PMID- 22963349
TI  - Air pollution particulate matter collected from an Appalachian mountaintop mining
      site induces microvascular dysfunction.
AB  - OBJECTIVE: Air pollution PM is associated with cardiovascular morbidity and
      mortality. In Appalachia, PM from mining may represent a health burden to this
      sensitive population that leads the nation in cardiovascular disease, among
      others. Cardiovascular consequences following inhalation of PM(MTM) are unclear,
      but must be identified to establish causal effects. METHODS: PM was collected
      within 1 mile of an active MTM site in southern WV. The PM was extracted and was
      primarily <10 MUm in diameter (PM10), consisting largely of sulfur (38%) and
      silica (24%). Adult male rats were IT with 300 MUg PM(MTM) . Twenty-four hours
      following exposure, rats were prepared for intravital microscopy, or isolated
      arteriole experiments. RESULTS: PM(MTM) exposure blunted endothelium-dependent
      dilation in mesenteric and coronary arterioles by 26%, and 25%, respectively, as
      well as endothelium-independent dilation. In vivo, PM(MTM) exposure inhibited
      endothelium-dependent arteriolar dilation (60% reduction). alpha-adrenergic
      receptor blockade inhibited PVNS-induced vasoconstriction in exposed animals
      compared with sham. CONCLUSIONS: These data suggest that PM(MTM) exposure impairs
      microvascular function in disparate microvascular beds, through alterations in NO
      mediated dilation and sympathetic nerve influences. Microvascular dysfunction may
      contribute to cardiovascular disease in regions with MTM sites.

PMID- 22963351
TI  - Globalization of clinical trials - where are we heading?
AB  - The last decade has witnessed a greater transparency in clinical research with
      the advent of clinical trial registries. The aim of the study was to describe the
      trends in the globalization of clinical trials in the last five years. We
      performed an internet search using the WHO International clinical trials registry
      platform (WHO ICTRP) to identify the clinical trials conducted from January 2007
      to December 31, 2011 among 25 countries. Among the 25 countries, the United
      States, Japan and Germany occupy the top positions in the total number of
      clinical trials conducted. Clinical trials in the US (36312) constituted 31.5% of
      the total number of trials performed during this period. However over a period of
      five years both US and Western Europe appear to show a decline, while the
      emerging countries show a rise in clinical trials registered. Among the emerging
      countries China, India and Republic of Korea are most active regions involved in
      clinical trials. Cancer, diabetes and respiratory diseases were most widely
      researched areas overall. Although the study confirms the transition in the
      clinical trials research towards emerging countries, the developed regions of the
      world still contribute to more than 70% of the trials registered worldwide.

PMID- 22963350
TI  - Proteomic profiling of tissue-engineered blood vessel walls constructed by
      adipose-derived stem cells.
AB  - Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and
      have been engineered into elastic small diameter blood vessel walls in vitro.
      However, the mechanisms involved in the development of three-dimensional (3D)
      vascular tissue remain poorly understood. The present study analyzed protein
      expression profiles of engineered blood vessel walls constructed by human ASCs
      using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry
      (MS). These results were compared to normal arterial walls. A total of 1701+/-15
      and 1265+/-26 protein spots from normal and engineered blood vessel wall
      extractions were detected by 2DE, respectively. A total of 20 spots with at least
      2.0-fold changes in expression were identified, and 38 differently expressed
      proteins were identified by 2D electrophoresis and ion trap MS. These proteins
      were classified into seven functional categories: cellular organization, energy,
      signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others.
      These results demonstrated that 2DE, followed by ion trap MS, could be
      successfully utilized to characterize the proteome of vascular tissue, including
      tissue-engineered vessels. The method could also be employed to achieve a better
      understanding of differentiated smooth muscle protein expression in vitro. These
      results provide a basis for comparative studies of protein expression in vascular
      smooth muscles of different origin and could provide a better understanding of
      the mechanisms of action needed for constructing blood vessels that exhibit
      properties consistent with normal blood vessels.

PMID- 22963352
TI  - Predicting doubly labeled water energy expenditure from ambulatory activity.
AB  - The purpose of this study was to evaluate the potential for using accelerometer
      determined ambulatory activity indicators (steps per day and cadence) to predict
      total energy expenditure (TEE) and physical activity energy expenditure (PAEE)
      derived from doubly labeled water (DLW). Twenty men and 34 women (20-36 years of
      age) provided complete anthropometric, accelerometer, resting metabolic rate
      (RMR), and DLW data. TEE and PAEE were determined for the same week that
      accelerometers were worn during waking hours. Accelerometer data included mean
      steps per day, peak 30-min cadence (average steps per minute for the highest 30
      min of the day), and time spent in each incremental cadence band: 0
      (nonmovement), 1-19 (incidental movement), 20-39 (sporadic movement), 40-59
      (purposeful steps), 60-79 (slow walking), 80-99 (medium walking), 100-119 (brisk
      walking), and 120+ steps.min(-1) (indicative of all faster ambulatory
      activities). Regression analyses were employed to develop sex-specific equations
      for predicting TEE and PAEE. The final model predicting TEE included body weight,
      steps per day, and time in incremental cadence bands and explained 79% (men) and
      65% (women) of the variability. The final model predicting PAEE included peak 30
      min cadence, steps per day, and time in cadence bands and explained 76% (men) and
      46% (women) of the variability. Time in cadence bands alone explained 39%-73% of
      the variability in TEE and 30%-63% of the variability in PAEE. Prediction models
      were stronger for men than for women.

PMID- 22963353
TI  - Gas-induced formation of Cu nanoparticle as catalyst for high-purity straight and
      helical carbon nanofibers.
AB  - The facile preparation of high-purity carbon nanofibers (CNFs) remains
      challenging due to the high complexity and low controllability in reaction. A
      novel approach using gas-induced formation of Cu crystals to control the growth
      of CNFs is developed in this study. By adjusting the atmospheric composition,
      controllable preparation of Cu nanoparticles (NPs) with specific size and shape
      is achieved, and they are further used as a catalyst for the growth of straight
      or helical CNFs with good selectivity and high yield. The preparation of Cu NPs
      and the formation of CNFs are completed by a one-step process. The inducing
      effect of N(2), Ar, H(2), and C(2)H(2) on the formation of Cu NPs is
      systematically investigated through a combined experimental and computational
      approach. The morphology of CNFs obtained under different conditions is
      rationalized in terms of Cu NP and CNF growth models. The results suggest that
      the shapes of CNFs, namely, straight or helical, depend closely on the size,
      shape, and facet activity of Cu NPs, while such a gas-inducing method offers a
      simple way to control the formation of Cu NPs.

PMID- 22963355
TI  - International conference on quantitative genetics 4: big science for complex
      traits.

PMID- 22963354
TI  - Improving diet, physical activity and other lifestyle behaviours using computer
      tailored advice in general practice: a randomised controlled trial.
AB  - BACKGROUND: The adoption and maintenance of healthy behaviours is essential in
      the primary prevention of chronic non-communicable diseases. This study evaluated
      the effectiveness of a minimal intervention on multiple lifestyle factors such as
      diet, physical activity, smoking and alcohol, delivered through general practice,
      using computer-tailored feedback. METHODS: Adult patients visiting 21 general
      practitioners in Brisbane, Australia, were surveyed about ten health behaviours
      that are risk factors for chronic, non-communicable diseases. Those who completed
      the self-administered baseline questionnaire entered a randomised controlled
      trial, with the intervention group receiving computer-tailored printed advice,
      targeting those health behaviours for which respondents were not meeting current
      recommendations. The primary outcome was change in summary lifestyle score
      (Prudence Score) and individual health behaviours at three months. A repeated
      measures analysis compared change in these outcomes in intervention and control
      groups after adjusting for age and education. RESULTS: 2306 patients were
      randomised into the trial. 1711 (76%) returned the follow-up questionnaire at 3
      months. The Prudence Score (10 items) in the intervention group at baseline was
      5.88, improving to 6.25 at 3 months (improvement = 0.37), compared with 5.84 to
      5.96 (improvement = 0.12) in the control group (F = 13.3, p = 0.01). The
      intervention group showed improvement in meeting recommendations for all
      individual health behaviours compared with the control group. However, these
      differences were significant only for fish intake (OR 1.37, 95% CI 1.11-1.68),
      salt intake (OR 1.19, 95% CI 1.05-1.38), and type of spread used (OR 1.28, 95% CI
      1.06-1.51). CONCLUSION: A minimal intervention using computer-tailored feedback
      to address multiple lifestyle behaviours can facilitate change and improve
      unhealthy behaviours. Although individual behaviour changes were modest, when
      implemented on a large scale through general practice, this intervention appears
      to be an effective and practical tool for population-wide primary prevention.
      TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry:
      ACTRN12611001213932.

PMID- 22963356
TI  - Accuracies of estimated breeding values from ordinary genetic evaluations do not
      reflect the correlation between true and estimated breeding values in selected
      populations.
AB  - The accuracy of estimated breeding values (EBVs) is an important parameter in
      livestock genetic improvement. It is used to calculate response to selection and
      to express the credibility of individual EBVs. Although it is well-known that
      selection reduces accuracy, this effect is not well-studied and accuracies from
      genetic evaluations are not adjusted for selection. This work investigates the
      effect of selection on accuracy of EBVs estimated using best linear unbiased
      predictors. Results show that accuracies in a selected population may be
      considerably smaller than the ordinary accuracy from genetic evaluation. Accuracy
      of the parent average is dramatically reduced by selection, up to a factor of
      three. Expressions for equilibrium accuracies in selected populations are
      presented and depend only on the unselected accuracy and the intensity of
      selection. Thus, schemes with the same unselected accuracy and intensity of
      selection also have the same equilibrium accuracy and response to selection. At
      the same unselected accuracy, therefore, schemes based on between-family
      information do not show greater reduction in response and accuracy because of the
      Bulmer effect. An example shows that benefit of genomic selection may be
      underestimated when the effect of selection on accuracy is ignored. Finally, this
      work argues that the SE of an EBV and the correlation between true and EBVs are
      different things, and that accuracies should not be adjusted for selection when
      they primarily serve to indicate the SEs of EBVs.

PMID- 22963357
TI  - Analysing quantitative parent-of-origin effects with examples from ultrasonic
      measures of body composition In Australian beef cattle.
AB  - Parent-of-origin effects arise when an individual's genes are modified during
      gametogenesis. Commonly known as imprinting, affected genes may be completely, or
      partially, suppressed. Individual loci in mice, human and sheep are known to be
      imprinted, and the quantitative effects of imprinted loci have been found for
      many carcass traits in cattle and pigs. Differentiating between five types of
      loci - direct additive loci and partially and completely imprinted loci by sires
      and dams - is not possible as their effects are confounded such that only three
      of seven parameters can be estimated. An analysis of Australian Hereford and
      Angus heifers and bulls for four ultrasonic measures of body composition - eye
      muscle area, rib fat, rump fat and intramuscular fat per cent - found parent-of
      origin effects for both parents in most trait-gender data sets and that they were
      an average of 28% of the total genetic variance. No parent-of-origin effects were
      found for Hereford bull intramuscular fat per cent and the maternal parent-of
      origin effects were not significant for Angus Heifer eye muscle area.

PMID- 22963358
TI  - Influence of model specifications on the reliabilities of genomic prediction in a
      Swedish-Finnish red breed cattle population.
AB  - Using a combined multi-breed reference population, this study explored the
      influence of model specification and the effect of including a polygenic effect
      on the reliability of genomic breeding values (DGV and GEBV). The combined
      reference population consisted of 2986 Swedish Red Breed (SRB) and Finnish
      Ayrshire (FAY) dairy cattle. Bayesian methodology (common prior and mixture
      models with different prior distribution settings for the marker effects) as well
      as a best linear unbiased prediction with a genomic relationship matrix [genomic
      best linear unbiased predictor (GBLUP)] was used in the prediction of DGV.
      Mixture models including a polygenic effect were used to predict GEBV. In total,
      five traits with low, high and medium heritability were analysed. For the models
      using a mixture prior distribution, reliabilities of DGV tended to decrease with
      an increasing proportion of markers with small effects. The influence of the
      inclusion of a polygenic effect on the reliability of DGV varied across traits
      and model specifications. Average correlation between DGV with the Mendelian
      sampling term, across traits, was highest (R(2) = 0.25) for the GBLUP model and
      decreased with increasing proportion of markers with large effects. Reliabilities
      increased when DGV and parent average information were combined in an index. The
      GBLUP model with the largest gain across traits in the reliability of the index
      achieved the highest DGV mean reliability. However, the polygenic models showed
      to be less biased and more consistent in the estimation of DGV regardless of the
      model specifications compared with the mixture models without the polygenic
      effect.

PMID- 22963359
TI  - Reaction norms and genotype-by-environment interaction in the German Holstein
      dairy cattle.
AB  - Reaction norm random regression sire models were used to study genotype-by
      environment interactions (G * E) in the German Holstein dairy cattle population.
      Around 2300 sires with a minimum of 50 daughters per sire and seven first
      lactation test day observations per daughter were analysed. Corrected test day
      records for milk yield, protein yield, fat yield and somatic cell score (SCS)
      were used. Herd test day solutions for milk traits, milk energy yield or SCS were
      used as environmental descriptors. Second-order orthogonal polynomial regressions
      were applied to the sire effects. The results revealed significant slope
      variances of the reaction norms, which caused a non-constant additive genetic
      variance across the environmental ranges considered. This pointed to the presence
      of minor G * E effects. The additive genetic variance increased when the
      environment improved, that is, higher (lower) herd test day solutions for milk
      traits (SCS). This was also influenced by pure scaling effects, because the non
      genetic variance increased in an improved environment and the heritability was
      less influenced by the environment. The G * E effects caused very little
      reranking of the sires for the environmental range considered in this study.

PMID- 22963360
TI  - Genetic analyses of new movement traits using detailed evaluations of warmblood
      foals and mares.
AB  - Detailed movement evaluations of warmblood foals and mares were performed in
      connection with regular breeding events of the Oldenburg horse breeding societies
      in 2009 and 2010. Unfavourable movement characteristics considered indicative for
      impaired balance were noted by a special judge (SJ) and the regular judges of the
      breeding events (RJ) and served as the basis for definition of new movement
      traits. Detailed movement information on 3374 foals and 2844 mares showed that
      more severe findings like irregular motion pattern in hind legs or irregularity
      in general motion pattern occurred only sporadically (prevalences of 1-2%).
      Irregular tail tone or posture was documented for 4% of the foals and 5% of the
      mares, resulting in prevalences of the comprehensive trait indications of
      imbalance (IMB) of 6.2% (foals) and 5.5% (mares). Binary coding was used for all
      traits, and genetic parameters were estimated bivariately in linear animal models
      with residual maximum likelihood. Comparative analyses between judges revealed
      that differences between trait definitions of SJ and RJ were larger in the mares
      than in the foals, but justified combined use of SJ and RJ information in both
      age groups. Heritability estimates for the movement traits ranged on the original
      scale from 0.02 to 0.26 in the foals and from 0.03 to 0.12 in the mares, with
      heritabilities for IMB on the underlying liability scale of 0.46 (foals) and 0.22
      (mares). Comparative analyses between age groups indicated that common genetic
      factors may be responsible for findings of impaired balance in foals and mares.
      The results implied that horse breeding may benefit from using the early
      available information on the movement of foals obtained by detailed movement
      evaluations, although favourable combination of foal and mare data in future
      genetic evaluations may require refined recording of unfavourable movement
      characteristics in the adult horses.

PMID- 22963361
TI  - Heritability estimates for racing performance in Japanese Thoroughbred racehorses
      using linear and non-linear model analyses.
AB  - This study evaluated the differences between linear and non-linear modelled
      heritability estimates of racing performance based on lifetime earnings (LE) and
      lifetime ranking (LR) in Japanese Thoroughbred racehorses. The heritability
      estimate (h(2) = 0.25) obtained from a non-linear model based on formal Japan
      Racing Association ranking was much higher than that obtained from a linear model
      based on the original trait phenotype (h(2) = 0.11). The linear models showed
      slightly higher heritability estimates under the trait categorizations than under
      the original phenotypes, while the non-linear categorical trait models showed
      much higher heritability estimates than the linear models, especially for binary
      trait categorizations (h(2) = 0.34) with non-winning and winning horses. The
      binary trait categorizations were consistent with the case and control
      classifications in the previous genome-wide association study (GWAS), which
      identified possible sequence variants on ECA18 that affect racing performance in
      Japanese Thoroughbred racehorses. Those findings suggested that the different
      heritability estimates obtained from several trait categorizations would reflect
      the possible presence of susceptibility gene segregations in the analyzed
      population, indicating that heritability estimates from non-linear models are
      useful for the selection of case and control populations in GWAS.

PMID- 22963362
TI  - Reciprocal translocations in cattle: frequency estimation.
AB  - Chromosomal anomalies, like Robertsonian and reciprocal translocations, represent
      a big problem in cattle breeding as their presence induces, in the carrier
      subjects, a well-documented fertility reduction. In cattle, reciprocal
      translocations (RCPs, a chromosome abnormality caused by an exchange of material
      between non-homologous chromosomes) are considered rare as to date only 19
      reciprocal translocations have been described. In cattle, it is common knowledge
      that the Robertsonian translocations represent the most common cytogenetic
      anomalies, and this is probably due to the existence of the endemic 1;29
      Robertsonian translocation. However, these considerations are based on data
      obtained using techniques that are unable to identify all reciprocal
      translocations, and thus, their frequency is clearly underestimated. The purpose
      of this work is to provide a first realistic estimate of the impact of RCPs in
      the cattle population studied, trying to eliminate the factors that have caused
      an underestimation of their frequency so far. We performed this work using a
      mathematical as well as a simulation approach and, as biological data, we
      considered the cytogenetic results obtained in the last 15 years. The results
      obtained show that only 16% of reciprocal translocations can be detected using
      simple Giemsa techniques, and consequently, they could be present in no <0.14% of
      cattle subjects, a frequency five times higher than that shown by de novo
      Robertsonian translocations. This data is useful to open a debate about the need
      to introduce a more efficient method to identify RCP in cattle.

PMID- 22963363
TI  - LDSO: a program to simulate pedigrees and molecular information under various
      evolutionary forces.
AB  - Simulations are a major tool to evaluate new statistical methods and optimize
      experimental designs in the genomic era. However, this can only be achieved when
      the simulations are close enough to reality, as well as diverse enough to be
      realistic. For mapping studies, it is thus critical to re-create as much as
      possible the forces generating linkage (mutation, random drift, changes in
      population sizes, selection and pedigree structure) and the mechanisms producing
      trait genetic architecture (additivity, dominance, epistasis). We present here a
      computer program (ldso) simulating these phenomena. Optional outputs provide
      statistics on the linkage disequilibrium (LD) structure and the identity by
      descent between chromosomal segments, facilitating further data analyses.
      Furthermore, ldso enables the simulation of genomic data in known pedigrees,
      which sticks as precisely as possible to recent population history and structures
      of the long-range LD, allowing optimization of fine-mapping strategies.

PMID- 22963365
TI  - Development of novel bepotastine salicylate salt bioequivalent to the commercial
      bepotastine besilate in beagle dogs.
AB  - To develop a novel salt form of bepotastine with bioequivalent to the commericial
      bepostastine besilate, bepostastine salicylate was prepared and its
      physicochemical properties were investigated. Furthermore, the bepotastine
      salicylate-loaded tablet was prepared by the wet granulation method, and the
      dissolution and bioavailability in beagle dogs were evaluated compared to the
      bepotastine besilate-loaded commercial product. Bepotastine salicylate improved
      the solubility of bepotastine, and the extent of solubility improvement by
      salicylate form was similar to that by besilate form. However, this novel salt
      exhibited negligible hygroscopicity similar to besilate form, and showed slightly
      higher melting point than besilate form. It was stable in various pH solutions.
      Furthermore, the bepotastine salicylate-loaded tablet composed of bepotastine
      salicylate, microcrystalline cellulose, D-mannitol, povidone, sodium starch
      glycolate and sodium stearyl fumarate at the weight ratio of
      9.63/60.97/38/3.6/6/1.8 showed similar dissolution to the bepotastine besilate
      loaded commercial product in water, pH 1.2, pH 4.0 and pH 6.8 and was
      bioequivalent to the commercial product in beagle dogs. Thus, this bepotastine
      salicylate-loaded tablet would be a promising candidate with bioequivalence to
      the bepotastine besilate-loaded commercial product.

PMID- 22963364
TI  - Identifying the mechanisms of intron gain: progress and trends.
AB  - Continued improvements in Next-Generation DNA/RNA sequencing coupled with
      advances in gene annotation have provided researchers access to a plethora of
      annotated genomes. Subsequent analyses of orthologous gene structures have
      identified numerous intron gain and loss events that have occurred both recently
      and in the very distant past. This research has afforded exceptional insight into
      the temporal and lineage-specific rates of intron gain and loss among various
      species throughout evolution. Numerous studies have also attempted to identify
      the molecular mechanisms of intron gain and loss. However, even after
      considerable effort, very little is known about these processes. In particular,
      the mechanism(s) of intron gain have proven exceptionally enigmatic and remain
      topics of considerable debate. Currently, there exists no definitive consensus as
      to what mechanism(s) may generate introns. Because many introns are known to
      affect gene expression, it is necessary to understand the molecular process(es)
      by which introns may be gained. Here we review the seven most commonly purported
      mechanisms of intron gain and, when possible, summarize molecular evidence for or
      against the occurrence of each of these mechanisms. Furthermore, we catalogue
      indirect evidence that supports the occurrence of each mechanism. Finally,
      because these proposed mechanisms fail to explain the mechanistic origin of many
      recently gained introns, we also look at trends that may aid researchers in
      identifying other potential mechanism(s) of intron gain.

PMID- 22963367
TI  - Oriented electrophoretic deposition of GdOCl nanoplatelets.
AB  - Electrophoretic deposition has emerged as a versatile and precisely tunable
      approach for the rapid deposition of conformal thin films of colloidal
      nanocrystals. The electrophoretic deposition of phosphor particles has assumed
      special significance in recent years as a commercially viable means toward the
      fabrication of large-area, ultrathin high-resolution emissive display screens.
      Here, we demonstrate that the anisotropic shape of colloidal ligand-passivated
      GdOCl nanoplatelets enables their assembly with remarkable substrate alignment
      and a high packing density upon electrophoretic deposition. GdOCl nanocrystals
      are promising candidates for phosphor applications given their low maximum phonon
      cutoff energy, robust chemical stability over prolonged periods of operation, and
      ability to promote efficacious phonon energy transfer to dopant ions.
      Potentiostatic deposition of GdOCl nanoplatelets from cyclohexane dispersions
      allows the deposition of individual nanoplatelets with their basal planes
      parallel to the electrode surface. Tuning the applied voltage and solution
      concentration allows control of film thickness, ranging up to several tens of
      micrometers. The high degree of particle alignment is attributed to anisotropic
      charge distribution and entrainment within electroosmotic flows established in
      the vicinity of the electrode surface. The oriented high-particle-density GdOCl
      nanoplatelet thin films are possible candidates for phosphor applications, which
      is illustrated by the green emission from a Tb-doped GdOCl thin film on indium
      tin oxide (ITO)-coated glass.

PMID- 22963366
TI  - Development of Land Use Regression models for PM(2.5), PM(2.5) absorbance, PM(10)
      and PM(coarse) in 20 European study areas; results of the ESCAPE project.
AB  - Land Use Regression (LUR) models have been used increasingly for modeling small
      scale spatial variation in air pollution concentrations and estimating individual
      exposure for participants of cohort studies. Within the ESCAPE project,
      concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were
      measured in 20 European study areas at 20 sites per area. GIS-derived predictor
      variables (e.g., traffic intensity, population, and land-use) were evaluated to
      model spatial variation of annual average concentrations for each study area. The
      median model explained variance (R(2)) was 71% for PM(2.5) (range across study
      areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56
      97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included
      between two and five predictor variables, with various traffic indicators as the
      most common predictors. Lower R(2) was related to small concentration variability
      or limited availability of predictor variables, especially traffic intensity.
      Cross validation R(2) results were on average 8-11% lower than model R(2).
      Careful selection of monitoring sites, examination of influential observations
      and skewed variable distributions were essential for developing stable LUR
      models. The final LUR models are used to estimate air pollution concentrations at
      the home addresses of participants in the health studies involved in ESCAPE.

PMID- 22963368
TI  - Intensified rehabilitation therapy and transitions to skilled nursing facilities
      in community-living seniors with acute medical illnesses.
AB  - AIM: To examine whether rehabilitation therapy type would be associated with
      transitions to skilled nursing facilities (SNF) in community-living seniors with
      acute medical illnesses. METHODS: Using administrative and clinical data,
      multivariate regression analysis examined the relationship between the extent of
      rehabilitation therapy and transitions to SNF in all participants, as well as
      participants by physical function at admission. RESULTS: In all participants
      (n=929), the intensified rehabilitation therapy was associated with a lower
      probability of transitions to SNF (14% vs 21%; odds ratio [OR] 0.59; 95%
      confidence intervals [CI] 0.22-0.96; P=0.02). In participants with mild physical
      limitations (n=270), less frequent transitions to SNF occurred when patients
      received intensified rehabilitation therapy [16% vs 23%; OR 0.46; 95% CI 0.17
      0.94; P=0.01]. In participants with moderate to severe physical limitations
      (n=265), the decreased frequency of transitions to SNF associated with
      rehabilitation therapy became more pronounced (18% vs 28%; OR 0.34; 95% CI 0.07
      0.89; P=0.004). By contrast, in participants without physical limitation (n=394),
      the number of transitions to SNF did not change significantly when they received
      intensified rehabilitation therapy (P=0.53). CONCLUSIONS: We found a significant
      relationship between intensified rehabilitation therapy and the decrease of
      transitions to SNF in community-living seniors with acute medical illness. The
      magnitude of this relationship increased in participants with more physical
      limitations, but not in participants without physical limitations at admission.

PMID- 22963371
TI  - P-N/P-P bond metathesis for the synthesis of complex polyphosphanes.
AB  - A unique hexaphosphane featuring a 2,2'-bi(1,2,3-triphosphacyclopentane) moiety
      (19) and an ethylene-bridged bis-isotetraphosphane (27(c,m)) were both
      selectively prepared in efficient one-pot syntheses from easily accessible
      tris(3,5-dimethyl-1-pyrazolyl)phosphane (14) and 1,2-bis(phenylphosphanyl)ethane
      (18(c,m)). The formation of 27(c,m) is an example of a highly efficient P-P bond
      formation via protolysis. In contrast, the formation of 19 comprises P-N/P-P bond
      metathesis steps. This constitutes a novel synthetic approach toward the
      preparation of complex polyphosphanes. Detailed spectroscopic investigations form
      the basis for a mechanistic understanding of this unprecedented methodology.
      Furthermore, the preparation of a unique dinuclear iron-carbonyl complex which
      features hexaphosphane 19 as a bridging ligand illustrates the potential use of
      complex polyphosphanes such as 19 as ligands in transition metal chemistry.

PMID- 22963370
TI  - Capturing the reaction pathway in near-atomic-resolution crystal structures of
      HIV-1 protease.
AB  - Snapshots of three consecutive steps in the proteolytic reaction of HIV-1
      protease (PR) were obtained in crystal structures at resolutions of 1.2-1.4 A.
      Structures of wild-type protease and two mutants (PR(V32I) and PR(I47V)) with
      V32I and I47V substitutions, which are common in drug resistance, reveal the gem
      diol tetrahedral intermediate, the separating N- and C-terminal products, and the
      C-terminal product of an autoproteolytic peptide. These structures represent
      three stages in the reaction pathway and shed light on the reaction mechanism.
      The near-atomic-resolution geometric details include a short hydrogen bond
      between the intermediate and the outer carboxylate oxygen of one catalytic Asp25
      that is conserved in all three structures. The two products in the complex with
      mutant PR(I47V) have a 2.2 A separation of the amide and carboxyl carbon of the
      adjacent ends, suggesting partial cleavage prior to product release. The complex
      of mutant PR(V32I) with a single C-terminal product shows density for water
      molecules in the other half of the binding site, including a partial occupancy
      water molecule interacting with the product carboxylate end and the carbonyl
      oxygen of one conformation of Gly27, which suggests a potential role of Gly27 in
      recycling from the product complex to the ligand-free enzyme. These structural
      details at near-atomic resolution enhance our understanding of the reaction
      pathway and will assist in the design of mechanism-based inhibitors as antiviral
      agents.

PMID- 22963372
TI  - Glucan affinity of starch synthase IIa determines binding of starch synthase I
      and starch-branching enzyme IIb to starch granules.
AB  - The sugary-2 mutation in maize (Zea mays L.) is a result of the loss of catalytic
      activity of the endosperm-specific SS (starch synthase) IIa isoform causing major
      alterations to amylopectin architecture. The present study reports a biochemical
      and molecular analysis of an allelic variant of the sugary-2 mutation expressing
      a catalytically inactive form of SSIIa and sheds new light on its central role in
      protein-protein interactions and determination of the starch granule proteome.
      The mutant SSIIa revealed two amino acid substitutions, one being a highly
      conserved residue (Gly522->Arg) responsible for the loss of catalytic activity
      and the inability of the mutant SSIIa to bind to starch. Analysis of protein
      protein interactions in sugary-2 amyloplasts revealed the same trimeric assembly
      of soluble SSI, SSIIa and SBE (starch-branching enzyme) IIb found in wild-type
      amyloplasts, but with greatly reduced activities of SSI and SBEIIb. Chemical
      cross-linking studies demonstrated that SSIIa is at the core of the complex,
      interacting with SSI and SBEIIb, which do not interact directly with each other.
      The sugary-2 mutant starch granules were devoid of amylopectin-synthesizing
      enzymes, despite the fact that the respective affinities of SSI and SBEIIb from
      sugary-2 for amylopectin were the same as observed in wild-type. The data support
      a model whereby granule-bound proteins involved in amylopectin synthesis are
      partitioned into the starch granule as a result of their association within
      protein complexes, and that SSIIa plays a crucial role in trafficking SSI and
      SBEIIb into the granule matrix.

PMID- 22963373
TI  - Clinical and genetic analysis of patients with X-linked hyper-IgM syndrome.

PMID- 22963374
TI  - A new flavonoid and other polar compounds from Galeopsis angustifolia Ehrh. ex
      Hoffm.
AB  - The analysis of the polar fraction of Galeopsis angustifolia Ehrh. ex Hoffm.
      indicates that the main components are iridoids and flavonoids. Six compounds
      were identified: a new flavonoid, 3'-hydroxy-isoscutellarein 7-O-[6'"acetyl-beta
      D-glucopyranosyl-(1 -> 2)-beta-D-glucopyranoside]; three iridoid glucosides:
      harpagide, acetyl harpagide and for the first time in this species, 8-epi
      loganin; two known acetylated flavonoid glycosides: 3'-hydroxy-4'-O
      methylisoscutellarein 7-O-[6'"acetyl-beta-D-allopyranosyl-(1 -> 2)-6"-acetyl-beta
      D-glucopyranoside], 3'-hydroxy-4'-O-methylisoscutellarein 7-O-[6'"acetyl-beta-D
      allopyranosyl-(1 -> 2)-beta-D-glucopyranoside]. Both flavonoids and iridoids are
      present in high amount; respectively, 16.7% and 4.5% of the crude extract.

PMID- 22963375
TI  - Developing a theory driven text messaging intervention for addiction care with
      user driven content.
AB  - The number of text messaging interventions designed to initiate and support
      behavioral health changes have been steadily increasing over the past 5 years.
      Messaging interventions can be tailored and adapted to an individual's needs in
      their natural environment-fostering just-in-time therapies and making them a
      logical intervention for addiction continuing care. This study assessed the
      acceptability of using text messaging for substance abuse continuing care and the
      intervention preferences of individuals in substance abuse treatment in order to
      develop an interactive mobile text messaging intervention. Fifty individuals
      enrolled in intensive outpatient substance abuse treatment completed an
      assessment battery relating to preferred logistics of mobile interventions,
      behavior change strategies, and types of messages they thought would be most
      helpful to them at different time points. Results indicated that 98% participants
      were potentially interested in using text messaging as a continuing care
      strategy. Participants wrote different types of messages that they perceived
      might be most helpful, based on various hypothetical situations often encountered
      during the recovery process. Although individuals tended to prefer benefit driven
      over consequence driven messages, differences in the perceived benefits of change
      among individuals predicted message preference. Implications for the development
      of mobile messaging interventions for the addictions are discussed. (PsycINFO
      Database Record (c) 2013 APA, all rights reserved).

PMID- 22963376
TI  - Evaluation of reflectance confocal microscopy in dermatophytosis.
AB  - Traditional diagnostic testing for dermatophyte infection currently requires skin
      scraping for light microscopy and/or fungal culture or skin biopsy.
      Immunofluorescent microscopy can also be used with calcofluor stain. All of these
      tests can be time-consuming to perform, require a waiting period for results and
      are invasive. This study aimed to define the in vivo reflectance confocal
      microscopy (RCM) features of superficial cutaneous fungal infections and to
      analyse concordance with microscopic examination. Totally, 45 patients, who were
      diagnosed with superficial cutaneous fungal infections according to the positive
      result of microscopic examination, were enrolled in this study. We selected three
      typical lesions examined by RCM, and then recorded the results. In the patients
      with the tinea manus and pedis, mycelium in stratum corneum was found by the RCM
      in 14 of 22 patients (14/22; 63.64%). In the patients with the tinea cruris,
      mycelium in stratum corneum was found by the RCM in 19 of 23 patients (19/23;
      82.61%). RCM seems to be useful for microscopic evaluation of mycelium features
      and may have a scientific value in study of superficial cutaneous fungal
      infections.

PMID- 22963377
TI  - The Tromso Eye Study: study design, methodology and results on visual acuity and
      refractive errors.
AB  - PURPOSE: To describe the study design and methodology of the Tromso Eye Study
      (TES), and to describe visual acuity and refractive error in the study
      population. METHODS: The Tromso Eye Study is a sub-study of the Tromso Study, a
      population-based multipurpose longitudinal study in the municipality of Tromso,
      Norway. The Tromso Eye Study was a part of the sixth survey of the Tromso Study,
      conducted from October 2007 through December 2008. The eye examination included
      information on self-reported eye diseases, assessment of visual acuity and
      refractive errors, retinal photography and optical coherence tomography. Retinal
      images were graded for diabetic retinopathy and age-related macular degeneration,
      and with computer-assisted measurements of arteriolar and venular diameters. In
      addition, TES researchers have access to the large comprehensive Tromso Study
      database including physical examination results, carotid artery ultrasound,
      electrocardiogram, bone densitometry, cognitive tests, questionnaires, DNA, blood
      and urine samples and more from the present and the five previous surveys.
      RESULTS: Visual acuity was assessed in 6459 subjects and refraction in 6566
      subjects aged 38-87 years. Snellen visual acuity <20/60 was found in 1.2% (95% CI
      0.95-1.5) of the participants and there was no gender difference. Visual
      impairment increased with age, and in the age group 80-87 years, the overall
      visual acuity <20/60 was 7.3% (95% CI 3.3-11.2). Spherical equivalent showed an
      increasing trend with age and there was no clinically relevant difference between
      men and women. Retinal photography was performed in 6540 subjects. CONCLUSION:
      Prevalence of visual impairment was low but increased with age. There was a trend
      towards hyperopia with age and no clinically relevant difference in refraction
      between the sexes. TES aims to provide epidemiological research on several eye
      and eye-related diseases. Owing to a comprehensive data collection, it has the
      opportunity to explore issues related to environmental factors, cognition and
      their interaction with diseases in this community.

PMID- 22963378
TI  - EXERCISE in pediatric autologous stem cell transplant patients: a randomized
      controlled trial protocol.
AB  - BACKGROUND: Hematopoietic stem cell transplantation is an intensive therapy used
      to improve survivorship and cure various oncologic diseases. However, this
      therapy is associated with high mortality rates and numerous negative side
      effects. The recovery of the immune system is a special concern and plays a key
      role in the success of this treatment. In healthy populations it is known that
      exercise plays an important role in immune system regulation, but little is known
      about the role of exercise in the hematological and immunological recovery of
      children undergoing hematopoietic stem cell transplant. The primary objective of
      this randomized-controlled trial (RCT) is to study the effect of an exercise
      program (in- and outpatient) on immune cell recovery in patients undergoing an
      autologous stem cell transplantation. The secondary objective is to determine if
      an exercise intervention diminishes the usual deterioration in quality of life,
      physical fitness, and the acquisition of a sedentary lifestyle. METHODS: This RCT
      has received approval from The Conjoint Health Research Ethics Board (CHREB) of
      the University of Calgary (Ethics ID # E-24476). Twenty-four participants treated
      for a malignancy with autologous stem cell transplant (5 to 18 years) in the
      Alberta Children's Hospital will be randomly assigned to an exercise or control
      group. The exercise group will participate in a two-phase exercise intervention
      (in- and outpatient) from hospitalization until 10 weeks after discharge. The
      exercise program includes strength, flexibility and aerobic exercise. During the
      inpatient phase this program will be performed 5 times/week and will be
      supervised. The outpatient phase will combine a supervised session with two home
      based exercise sessions with the use of the Wii device. The control group will
      follow the standard protocol without any specific exercise program. A range of
      outcomes, including quantitative and functional recovery of immune system,
      cytokine levels in serum, natural killer (NK) cells and their subset recovery and
      function, and gene expression of activating and inhibitory NK cell receptors,
      body composition, nutrition, quality of life, fatigue, health-related fitness
      assessment and physical activity levels will be examined, providing the most
      comprehensive assessment to date. DISCUSSION: We expect to find improvements in
      immunological recovery and quality of life, and decreased acquisition of
      sedentary behavior and fitness deconditioning. The comprehensive outcomes
      generated in this RCT will provide preliminary data to conduct a multisite study
      that will generate stronger outcomes. TRIAL REGISTRATION: Gov identification #
      NCT01666015.

PMID- 22963379
TI  - Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum.
AB  - BACKGROUND: Corynebacterium glutamicum contains the glycosylated C50 carotenoid
      decaprenoxanthin as yellow pigment. Starting from isopentenyl pyrophosphate,
      which is generated in the non-mevalonate pathway, decaprenoxanthin is synthesized
      via the intermediates farnesyl pyrophosphate, geranylgeranyl pyrophosphate,
      lycopene and flavuxanthin. RESULTS: Here, we showed that the genes of the
      carotenoid gene cluster crtE-cg0722-crtBIYeYfEb are co-transcribed and
      characterized defined gene deletion mutants. Gene deletion analysis revealed that
      crtI, crtEb, and crtYeYf, respectively, code for the only phytoene desaturase,
      lycopene elongase, and carotenoid C45/C50 epsilon-cyclase, respectively. However,
      the genome of C. glutamicum also encodes a second carotenoid gene cluster
      comprising crtB2I2-1/2 shown to be co-transcribed, as well. Ectopic expression of
      crtB2 could compensate for the lack of phytoene synthase CrtB in C. glutamicum
      DeltacrtB, thus, C. glutamicum possesses two functional phytoene synthases,
      namely CrtB and CrtB2. Genetic evidence for a crtI2-1/2 encoded phytoene
      desaturase could not be obtained since plasmid-borne expression of crtI2-1/2 did
      not compensate for the lack of phytoene desaturase CrtI in C. glutamicum
      DeltacrtI. The potential of C. glutamicum to overproduce carotenoids was
      estimated with lycopene as example. Deletion of the gene crtEb prevented
      conversion of lycopene to decaprenoxanthin and entailed accumulation of lycopene
      to 0.03 +/- 0.01 mg/g cell dry weight (CDW). When the genes crtE, crtB and crtI
      for conversion of geranylgeranyl pyrophosphate to lycopene were overexpressed in
      C. glutamicum DeltacrtEb intensely red-pigmented cells and an 80 fold increased
      lycopene content of 2.4 +/- 0.3 mg/g CDW were obtained. CONCLUSION: C. glutamicum
      possesses a certain degree of redundancy in the biosynthesis of the C50
      carotenoid decaprenoxanthin as it possesses two functional phytoene synthase
      genes. Already metabolic engineering of only the terminal reactions leading to
      lycopene resulted in considerable lycopene production indicating that C.
      glutamicum may serve as a potential host for carotenoid production.

PMID- 22963380
TI  - Diagnosis of tetralogy of Fallot and its variants in the late first and early
      second trimester: details of initial assessment and comparison with later fetal
      diagnosis.
AB  - OBJECTIVE: We sought to evaluate the completeness of echocardiographic diagnosis
      of fetal tetralogy of Fallot (fTOF) at 12-17 weeks gestation, and compare
      assessment and clinical outcomes to diagnoses made at >17 weeks gestation.
      METHODS: We identified all fTOF diagnoses made in our experience from 2003 to
      2008. Referral indication, anatomic detail by echocardiography and pregnancy
      outcomes were compared between fetuses diagnosed at <= 17 weeks (Group I) and >17
      weeks gestation (Group II). A 10-point scoring tool was applied retrospectively
      to the echocardiograms at initial diagnosis (1 point each was ascribed to
      visualization of right ventricular outflow obstruction, pulmonary valve,
      pulmonary arteries including dimensions, pulmonary arterial flow, systemic and
      pulmonary venous anatomy, atrioventricular valves, ductus arteriosus, ductus
      flow, aortic arch morphology, sidedness and flow). RESULTS: There were 10
      pregnancies in Group I (12-17 weeks) and 25 in Group II (mean gestation at
      diagnosis 23.5 +/- 5.7). The most common reason for referral was extracardiac
      pathology in Group I (80%) and suspected fetal heart disease on obstetric
      ultrasound in Group II (64%). Transabdominal imaging was adequate in about half
      of Group I studies. Mean anatomic diagnosis score in Group I was 6.1(range 2.5-9)
      and Group II was 8.4 (range 6.5-10). Elective pregnancy termination occurred in
      80% in Group I and 33% in Group II. CONCLUSIONS: fTOF can be diagnosed in first
      and early second trimesters with detailed anatomic assessment possible in most.
      Referral indication and pregnancy outcome differ considerably between early and
      later prenatal diagnosis of fTOF.

PMID- 22963381
TI  - Biorecognition layer engineering: overcoming screening limitations of nanowire
      based FET devices.
AB  - Detection of biological species is of great importance to numerous areas of
      medical and life sciences from the diagnosis of diseases to the discovery of new
      drugs. Essential to the detection mechanism is the transduction of a signal
      associated with the specific recognition of biomolecules of interest. Nanowire
      based electrical devices have been demonstrated as a powerful sensing platform
      for the highly sensitive detection of a wide-range of biological and chemical
      species. Yet, detecting biomolecules in complex biosamples of high ionic strength
      (>100 mM) is severely hampered by ionic screening effects. As a consequence, most
      of existing nanowire sensors operate under low ionic strength conditions,
      requiring ex situ biosample manipulation steps, that is, desalting processes.
      Here, we demonstrate an effective approach for the direct detection of
      biomolecules in untreated serum, based on the fragmentation of antibody-capturing
      units. Size-reduced antibody fragments permit the biorecognition event to occur
      in closer proximity to the nanowire surface, falling within the charge-sensitive
      Debye screening length. Furthermore, we explored the effect of antibody surface
      coverage on the resulting detection sensitivity limit under the high ionic
      strength conditions tested and found that lower antibody surface densities, in
      contrary to high antibody surface coverage, leads to devices of greater
      sensitivities. Thus, the direct and sensitive detection of proteins in untreated
      serum and blood samples was effectively performed down to the sub-pM
      concentration range without the requirement of biosamples manipulation.

PMID- 22963383
TI  - Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive
      rats.
AB  - BACKGROUND: The additive effects of obesity and metabolic syndrome on left
      ventricular (LV) maladaptive remodeling and function in hypertension are not
      characterized. METHODS: We compared an obese spontaneously hypertensive rat model
      (SHR-ob) with lean spontaneously hypertensive rats (SHR-lean) and normotensive
      controls (Ctr). LV-function was investigated by cardiac magnetic resonance
      imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was
      quantified and protein levels of phospholamban (PLB), Serca2a and glucose
      transporters (GLUT1 and GLUT4) were determined by immunohistochemistry. RESULTS:
      Systolic blood pressure was similar in SHR-lean and SHR-ob (252 +/- 7 vs. 242 +/-
      7 mmHg, p = 0.398) but was higher when compared to Ctr (155 +/- 2 mmHg, p < 0.01
      for both). Compared to SHR-lean and Ctr, SHR-ob showed impaired glucose tolerance
      and increased body-weight. In SHR-ob, LV-ejection fraction was impaired vs. Ctr
      (46.2 +/- 1.1 vs. 59.6 +/- 1.9%, p = 0.007). LV-enddiastolic pressure was more
      increased in SHR-ob than in SHR-lean (21.5 +/- 4.1 vs. 5.9 +/- 0.81 mmHg, p =
      0.0002) when compared to Ctr (4.3 +/- 1.1 mmHg, p < 0.0001 for both),
      respectively. Increased LV-fibrosis together with increased myocyte diameters and
      ANF gene expression in SHR-ob were associated with increased GLUT1-protein levels
      in SHR-ob suggestive for an upregulation of the GLUT1/ANF-axis. Serca2a-protein
      levels were decreased in SHR-lean but not altered in SHR-ob compared to Ctr. PLB
      phosphorylation was not altered. CONCLUSION: In addition to hypertension alone,
      metabolic syndrome and obesity adds to the myocardial phenotype by aggravating
      diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may
      be a useful model to develop new interventional and pharmacological treatment
      strategies for hypertensive heart disease and metabolic disorders.

PMID- 22963384
TI  - Solubility of iron from combustion source particles in acidic media linked to
      iron speciation.
AB  - In this study, iron solubility from six combustion source particles was
      investigated in acidic media. For comparison, a Chinese loess (CL) dust was also
      included. The solubility experiments confirmed that iron solubility was highly
      variable and dependent on particle sources. Under dark and light conditions, the
      combustion source particles dissolved faster and to a greater extent relative to
      CL. Oil fly ash (FA) yielded the highest soluble iron as compared to the other
      samples. Total iron solubility fractions measured in the dark after 12 h ranged
      between 2.9 and 74.1% of the initial iron content for the combustion-derived
      particles (Oil FA > biomass burning particles (BP) > coal FA). Ferrous iron
      represented the dominant soluble form of Fe in the suspensions of straw BP and
      corn BP, while total dissolved Fe presented mainly as ferric iron in the cases of
      oil FA, coal FA, and CL. Mossbauer measurements and TEM analysis revealed that Fe
      in oil FA was commonly presented as nanosized Fe(3)O(4) aggregates and Fe/S-rich
      particles. Highly labile source of Fe in corn BP could be originated from
      amorphous Fe form mixed internally with K-rich particles. However, Fe in coal FA
      was dominated by the more insoluble forms of both Fe-bearing aluminosilicate
      glass and Fe oxides. The data presented herein showed that iron speciation varies
      by source and is an important factor controlling iron solubility from these
      anthropogenic emissions in acidic solutions, suggesting that the variability of
      iron solubility from combustion-derived particles is related to the inherent
      character and origin of the aerosols themselves. Such information can be useful
      in improving our understanding on iron solubility from combustion aerosols when
      they undergo acidic processing during atmospheric transport.

PMID- 22963385
TI  - Metabolic parameters for ramp versus step incremental cycle ergometer tests.
AB  - The purpose of this study was to examine mean differences and the patterns of
      responses for oxygen uptake ([Formula: see text]O(2)), heart rate (HR), and
      rating of perceived exertion (RPE) for ramp (15 W.min(-1)) versus step (30 W
      increments every 2 min) incremental cycle ergometer tests. Fourteen subjects (age
      and body mass of 23.2 +/- 3.1 (mean +/- SD ) years and 71.1 +/- 10.1 kg,
      respectively) visited the laboratory on separate occasions. Two-way repeated
      measures ANOVAs with appropriate follow-up procedures, as well as paired t tests,
      were used to analyze the data. In addition, polynomial regression analyses were
      used to determine the patterns of responses for each dependent variable for the
      ramp and step tests. The ramp protocol resulted in lower mean [Formula: see
      text]O(2) and HR values at the common power outputs than the step protocol with
      no differences in RPE. The increased amount of work performed during the step
      (total work = 75.83 kJ) versus ramp (total work = 65.60 kJ) tests at the common
      power outputs may have contributed to the greater [Formula: see text]O(2) and HR
      values. The polynomial regression analyses showed that most subjects had the same
      patterns of responses for the ramp and step incremental tests for HR (86%) and
      RPE (93%) but different patterns for [Formula: see text]O(2) (71%). The findings
      from the present study suggested that the protocol selection for an incremental
      cycle ergometer test can affect the mean values for [Formula: see text]O(2) and
      HR, as well as the [Formula: see text]O(2) - power output relationship.

PMID- 22963386
TI  - From rumen to industry.
AB  - The rumen is one of the most complicated and most fascinating microbial
      ecosystems in nature. A wide variety of microbial species, including bacteria,
      fungi and protozoa act together to bioconvert (ligno)cellulosic plant material
      into compounds, which can be taken up and metabolized by the ruminant. Thus, the
      rumen perfectly resembles a solution to a current industrial problem: the
      biorefinery, which aims at the bioconversion of lignocellulosic material into
      fuels and chemicals. We suggest to intensify the studies of the ruminal microbial
      ecosystem from an industrial microbiologists point of view in order to make use
      of this rich source of organisms and enzymes.

PMID- 22963387
TI  - Rate of progression of Alzheimer's disease in younger versus older patients: a
      longitudinal single photon emission computed tomography study.
AB  - AIM: Although several researchers have examined the effect of age on disease
      progression in patients with Alzheimer's disease (AD), the results are
      controversial. We investigated the effect of age on the rate of progression of
      cognitive impairment and on regional cerebral blood flow (rCBF) deficits using
      longitudinal single photon emission computed tomography (SPECT) studies. METHODS:
      We divided 75 patients with AD who were followed up for 24-90 months into the
      younger AD group (n=32, age at initial examination <= 75 years) and the older AD
      group (n=43, age at initial examination >75 years). We assessed changes in Mini
      Mental State Examination (MMSE) scores and rCBF between initial and final
      examinations. RESULTS: The change in the annual MMSE score was greater in the
      younger AD group than in the older AD group. The mean annual MMSE score changes
      correlated significantly with age at the initial examination. The initial and
      follow-up SPECT studies showed more severe and extensive rCBF deficits in the
      younger AD group than in the older AD group. CONCLUSION: Our longitudinal SPECT
      study showed that the rate of progression of cognitive impairment and the rCBF
      deficits were higher in younger patients with AD than in older patients with AD.
      Therefore, age is an important factor to consider, not only in the diagnosis, but
      also in the treatment and prognosis of patients with AD.

PMID- 22963388
TI  - Effect of oriental medicine music therapy on patients with Hwa-byung: a study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Hwa-byung, a Korean culture-bound syndrome with both psychological
      and somatic symptoms, is also known as 'anger syndrome'. It includes various
      physical symptoms including anxiety, a feeling of overheating, a sensation of
      pressure on the chest, heart palpitations, respiratory stuffiness, insomnia, and
      anxiety. METHODS/DESIGN: The proposed study is a single-center, double-blind,
      randomized, controlled trial with two parallel arms: an oriental medicine music
      therapy (OMMT) group and a control music therapy (CMT) group. In total, 48
      patients will be enrolled into the trial. The first visit will be the screening
      visit. At baseline (visit 2), all participants fulfilling both the inclusion and
      the exclusion criteria will be split and randomly divided into two equal groups:
      the OMMT and the CMT (n = 24 each). Each group will receive treatment sessions
      over the course of 4 weeks, twice per week, for eight sessions in total. The
      primary outcome is the State-Trait Anxiety Inventory (STAI), and the secondary
      outcomes are the Hwa-byung scale (H-scale), the Center for Epidemiologic Studies
      Depression Scale (CES-D), the Hwa-byung visual analogue scale (H-VAS) for primary
      symptoms, the World Health Organization Quality of Life scale, brief version
      (WHOQOL-BREF), and levels of salivary cortisol. Patients will be asked to
      complete questionnaires at the baseline visit (visit 2), after the last treatment
      session (visit 9), and at 4 weeks after the end of all trial sessions (visit 10).
      From the baseline (visit 2) through the follow-up (visit 10), the entire process
      will take a total of 53 days. DISCUSSION: This proposed study targets patients
      with Hwa-byung, especially those who have exhibited symptoms of anxiety.
      Therefore, the primary outcome is set to measure the level of anxiety. OMMT is
      music therapy combined with traditional Korean medicinal theories. Unlike
      previously reported music therapies, for which patients simply listen to music
      passively, in OMMT, patients actively move their bodies and play the music.
      Because Hwa-byung is caused by an accumulation of blocked emotions and anger
      inside the body, OMMT, because of its active component, is expected to be more
      efficacious than pre-existing music therapies. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN11939282.

PMID- 22963389
TI  - Battlezone: An examination of the physiological responses, movement demands and
      reproducibility of small-sided cricket games.
AB  - As cricket training typically involves separate skill and conditioning sessions,
      this study reported on the movement demands, physiological responses and
      reproducibility of the demands of small-sided cricket games. Thirteen amateur,
      male cricket players (age: 22.8 +/- 3.5 years, height: 1.78 +/- 0.06 m, body
      mass: 78.6 +/- 7.1 kg) completed two sessions of a generic small-sided cricket
      game, termed Battlezone; consisting of six repeat 8-over bouts. Heart rate and
      movement demands were continuously recorded, whilst blood lactate concentration
      and perceived exertion were recorded after each respective bout. Batsmen covered
      the greatest distance (1147 +/- 175 m) and demonstrated the greatest mean
      movement speed (63 +/- 9 m . min-1) during each bout. The majority of time (65
      86%) was spent with a heart rate of between 51-85% HR(max) and a blood lactate
      concentration of 1.1-2.0 mmol . L-1. Rating of perceived exertion ranged between
      4.2-6.0. Movement demands and physiological responses did not differ between
      standardised sessions within respective playing positions (P > 0.05). The
      reliability for the majority of movement demands and physiological responses were
      moderate to high (CV: 5-17%; ICC: 0.48-1.00) within all playing positions. These
      results suggest that the physiological responses and movement characteristics of
      generic small-sided cricket games were consistent between sessions within
      respective playing positions.

PMID- 22963390
TI  - Impact of age, phenotype and cardio-renal function on plasma C-type and B-type
      natriuretic peptide forms in an adult population.
AB  - CONTEXT: In contrast to the cardiac hormones, atrial natriuretic peptide (ANP)
      and B-type natriuretic peptide (BNP), variations in plasma concentrations of C
      type natriuretic peptide (CNP) in healthy adults are ill-defined, limiting their
      clinical application. OBJECTIVE: Our objective was to define the effect of age,
      phenotype (gender, height, BMI), and cardiac and renal function on plasma CNPs in
      an adults population without renal or cardiovascular disease. DESIGN AND SETTING:
      This was a prospective cross-sectional observational study of adult volunteers,
      aged 21-80 years, randomly selected from the electoral roll. SUBJECTS AND
      METHODS: Plasma CNP and its associated aminoterminal propeptide (NTproCNP) were
      measured in 258 subjects and related to age, gender, height and plasma
      creatinine. Subgroup analyses seeking associations with cardiac function (plasma
      BNP and NTproBNP) and bone turnover bone-specific alkaline phosphatase (bALP)
      were also determined. RESULTS: Plasma concentrations of CNPs in men continued to
      decline from adolescent values to reach a nadir in the 5th decade after which
      values increased. Similar but less marked changes occurred in women. In both
      sexes, NTproCNP was inversely and independently correlated with height. In
      contrast to B-type natriuretic peptides (BNPs), NTproCNP was higher in men,
      significantly related to creatinine and positively related to bALP. CONCLUSIONS:
      Gender- and age-specific changes affect CNPs in adults. Inverse associations of
      NTproCNP with adult height, positive correlation with creatinine - and in
      contrast to CNP - no association with BNP are further unique findings
      distinguishing NTproCNP, which need to be considered in future studies.

PMID- 22963391
TI  - Engineered contractile skeletal muscle tissue on a microgrooved methacrylated
      gelatin substrate.
AB  - To engineer tissue-like structures, cells must organize themselves into three
      dimensional (3D) networks that mimic the native tissue microarchitecture.
      Microfabricated hydrogel substrates provide a potentially useful platform for
      directing cells into biomimetic tissue architecture in vitro. Here, we present
      microgrooved methacrylated gelatin hydrogels as a suitable platform to build
      muscle-like fibrous structures in a facile and highly reproducible fashion.
      Microgrooved hydrogel substrates with two different ridge sizes (50 and 100 MUm)
      were fabricated to assess the effect of the distance between engineered myofibers
      on the orientation of the bridging C2C12 myoblasts and the formation of the
      resulting multinucleated myotubes. It was shown that although the ridge size did
      not significantly affect the C2C12 myoblast alignment, the wider-ridged
      micropatterned hydrogels generated more myotubes that were not aligned to the
      groove direction as compared to those on the smaller-ridge micropatterns. We also
      demonstrated that electrical stimulation improved the myoblast alignment and
      increased the diameter of the resulting myotubes. By using the microstructured
      methacrylated gelatin substrates, we built free-standing 3D muscle sheets, which
      contracted when electrically stimulated. Given their robust contractility and
      biomimetic microarchitecture, engineered tissues may find use in tissue
      engineering, biological studies, high-throughput drug screening, and biorobotics.

PMID- 22963392
TI  - Emotion regulation difficulties in anorexia nervosa: Relationship to self
      perceived sensory sensitivity.
AB  - Changes in sensation (e.g., prickly skin) are crucial constituents of emotional
      experience, and the intensity of perceived changes has been linked to emotional
      intensity and dysregulation. The current study examined the relationship between
      sensory sensitivity and emotion regulation among adults with anorexia nervosa
      (AN), a disorder characterised by disturbance in the experience of the body.
      Twenty-one individuals with AN, 20 individuals with AN who were weight-restored,
      and 23 typical controls completed self-report measures of sensory sensitivity and
      emotion regulation. AN participants reported heightened sensory sensitivity and
      greater difficulty regulating emotions relative to controls. Self-perceived
      sensory sensitivity was associated with greater emotion dysregulation. Weight
      restored AN participants reported greater ability to regulate emotions than their
      currently underweight counterparts, despite heightened sensitivity. Findings
      suggest that hypersensitivity may be a persisting feature in AN, and that weight
      restoration may involve improved ability to cope with sensation.

PMID- 22963393
TI  - Comparison of p450 enzymes between cynomolgus monkeys and humans: p450
      identities, protein contents, kinetic parameters, and potential for inhibitory
      profiles.
AB  - Cynomolgus monkeys are used to predict human pharmacokinetic and/or toxic
      profiles in the drug developmental stage. Cynomolgus P450s exhibit a high degree
      of identity (more than 90%) in both cDNA and amino acid sequences with
      corresponding human P450s. CYP3A protein predominantly exists in cynomolgus
      monkey liver microsomes, followed by CYP2A, CYP2C, CYP2B6, CYP2E1, and CYP2D.
      There are many similarities of metabolic properties in cytochrome P450s between
      cynomolgus monkeys and humans, but the species differences between cynomolgus
      monkey and human P450s are clearly present in substrate specificity and inhibitor
      selectivity. Diclofenac 4'-hydroxylation (DFOH) in monkey liver and intestinal
      microsomes shows much lower activities compared with those in human liver and
      intestinal microsomes. Sulfaphenazole strongly inhibits DFOH in human liver
      microsomes, but does not effectively inhibit DFOH in monkey liver and intestinal
      microsomes. Cynomolgus CYP2C19 exhibits higher activity for DFOH than cynomolgus
      CYP2C9 although this reaction is a marker reaction of human CYP2C9. On the other
      hand, cynomolgus CYP2C76 orthologue is not expressed in humans and shows 70-72%
      identity in amino acid sequences of human CYP2C subfamilies. Cynomolgus CYP2C76
      metabolizes non-CYP2C substrates, 7-ethoxyresorufin (human CYP1A substrate) and
      bufuralol (human CYP2D6 substrate). In addition, cynomolgus CYP3A4 and CYP3A5
      also exhibits wider substrate selectivity toward human CYP2D6 and CYP2E1
      substrates. These enzymes may be responsible for species difference in drug
      metabolism between cynomolgus monkeys and humans. The comparative data presented
      here can be helpful for designing in vivo metabolic assays using cynomolgus
      monkeys in terms of substrate specificity and inhibitor selectivity.

PMID- 22963394
TI  - Biopsychosocial predictors of prognosis in musculoskeletal disorders: a
      systematic review of the literature (corrected and republished) *.
AB  - PURPOSE: To review the prognostic factors of musculoskeletal disorders while
      adopting a multidimensional perspective and including studies on various
      pertinent outcomes to the adjustment process. We also aimed to highlight the
      overall and phase-specific evidence. METHOD: We searched the Psychinfo and Ovid
      Medline(R) databases as well as pertinent periodicals and reviews and retained
      prospective studies of subjects suffering from specific or non-specific
      musculoskeletal pain that adopted multivariate statistical analysis. RESULTS: We
      selected 105 studies, of which 68 included biopsychosocial and sociodemographic
      variables. For those studies using a biopsychosocial framework, we determined the
      level of evidence for every prognostic factor with each outcome. Strong evidence
      was found for recovery expectations and disability management with work
      participation outcomes. With disability outcomes, strong evidence was also found
      for recovery expectations, coping and somatization. Comorbidity and duration of
      episode strongly predicted pain outcomes. Some differences coinciding with phases
      of chronicity were also identified. CONCLUSION: Although uncertainty remains
      about the role of many prognostic factors, we found strong evidence to support
      the predictive value of clinically significant variables. There is, however, a
      need for additional research and replication, adopting more homogenous models and
      measurement methods.

PMID- 22963395
TI  - Multichannel decoding for phase-coded SSVEP brain-computer interface.
AB  - We propose a complex-valued multilayer feedforward neural network classifier for
      decoding of phase-coded information from steady-state visual evoked potentials.
      To optimize the performance of the classifier we supply it with two filter-based
      feature selection strategies. The proposed approaches could be used for a phase
      coded brain-computer interface, enabling to encode several targets using only one
      stimulation frequency. The proposed classifier is a multichannel one, which
      distinguishes our approach from the existing single-channel ones. We show that
      the proposed approach outperforms others in terms of accuracy and length of the
      data segments used for decoding. We show that the decoding based on one optimally
      selected channel yields an inferior performance compared to the one based on
      several features, which supports our argument for a multichannel approach.

PMID- 22963396
TI  - Clinical and laboratory findings in patients with oliguric and non-oliguric
      hantavirus haemorrhagic fever with renal syndrome: an analysis of 128 patients.
AB  - Patients with haemorrhagic fever with renal syndrome (HFRS) may present without
      significant oliguria. We compared different initial clinical symptoms and
      laboratory findings in patients who developed oliguric acute renal failure (ARF)
      with those in patients who did not develop oliguric ARF. Overall, 128 patients
      with serologically confirmed HFRS were hospitalized at the University Hospital
      for Infectious Disease, Zagreb, Croatia between January 1999 and December 2010.
      Clinical signs and laboratory findings were extracted from medical charts, and
      were assessed for their relationship to the development of oliguric ARF. Puumala
      virus infection was diagnosed in 101 (79%) patients, and Dobrava-Belgrade virus
      infection in 27 (21%). Oliguria or anuria developed in 30% of patients. We
      identified the following risk factors for the development of oliguria and anuria
      on multivariable analysis: conjunctival hyperaemia or bleeding (relative risk
      (RR) 1.84, 95% CI 1.09-3.10; p 0.023), diarrhoea (RR 1.45, 95% CI 1.07-1.97; p
      0.017), serum sodium of <=133 mM (RR 2.21, 95% CI 1.34-3.64; p 0.002), and
      dipstick protein value of >1.5 g/L (RR 1.59, 95% CI 1.09-2.33; p 0.016), as well
      as hiking in the forest (RR 1.92, 95% CI 1.13-3.26; p 0.016). Our findings may
      help physicians in the earlier identification of patients with a more severe form
      of HFRS caused by Puumala and Dobrava-Belgrade viruses. Particular attention
      should be given to findings such as conjunctival hyperaemia or bleeding,
      diarrhoea, a low serum sodium level, and proteinuria.

PMID- 22963397
TI  - Autophagy negatively regulates cancer cell proliferation via selectively
      targeting VPRBP.
AB  - There have been multiple lines of evidence suggesting that autophagy selectively
      targets signalling proteins and regulates cancer cell signalling in addition to
      bulk clearance of long-lived proteins and organelles. Protein degradation through
      autophagy requires receptor protein LC3B to sequester the substrates into the
      autophagosome. In the present study, we screened LC3B (light-chain 3B)-binding
      partners and identified autophagic substrates in cancer cells. With lung cancer
      NCI-H1975 and oesophageal cancer KYSE30 cell lines as models, we found that VPRBP
      (viral protein R-binding protein) was a novel LC3B-binding protein through GST
      (glutathione transferase)-LC3B pull-down combined with LC-MS/MS (liquid
      chromatography-tandem MS) methods. Co-immunoprecipitation assay showed that VPRBP
      LC3/p62 were in the same protein complex as the two cell lines. Induction of
      autophagy led to a down-regulation of VPRPB, which could be rescued by the
      inhibition of autophagy degradation by BFA1 (bafilomycin A1) and by the
      disruption of autophagy through ATG5-knockdown. We also found that induction of
      autophagy promotes VPRBP-LC3/p62 interaction. Immunohistochemical examination of
      human NSCLC (non-small cell lung cancer) tissues showed that VPRBP was positively
      correlated with p62 and negatively correlated with LC3B. Moreover, p62 and VPRBP
      were associated with poor prognosis in lung ADC (adenocarcinoma) (p62, P=0.019;
      VPRBP, P=0.005). Patients with low expression of both p62 and VPRBP showed the
      best prognosis.

PMID- 22963398
TI  - Mutation spectrum of RB1 gene in Korean bilateral retinoblastoma patients using
      direct sequencing and gene dosage analysis.

PMID- 22963399
TI  - The syndrome of degenerative calcific aortic stenosis: prevalence of multiple
      pathophysiologic disorders in association with valvular stenosis and their
      implications.
AB  - BACKGROUND: We hypothesized that degenerative calcific aortic stenosis (DCAS) is
      a syndrome influenced by factors beyond aortic valve stenosis (AS). The aim of
      this study was to assess how frequently DCAS is complicated by increased vascular
      load, systolic and/or diastolic left ventricular (LV) dysfunction, and comorbid
      disorders. METHODS: In 215 consecutive patients > 60 years of age with severe and
      moderate AS, we analyzed systemic arterial compliance, global hemodynamic load,
      LV ejection fraction (EF), the presence of diastolic dysfunction, and other
      valvular or systemic disorders. RESULTS: A total of 164 patients had severe AS
      and 51 had moderate AS. In patients with severe AS, the prevalence of increased
      vascular load was 42%; LV systolic and diastolic dysfunction was present in 27%
      and 42%; other valve diseases in 23%; and comorbid disorders in 82%. In the
      moderate AS group, abnormal vascular load was found in 52%; LV systolic and
      diastolic dysfunction was prevalent in 26% and 31%; other valve diseases in 17%;
      and comorbid disorders in 78% patients. More than half the patients in both
      groups had symptoms. In both severe and moderate AS groups, the prevalence of
      increased vascular load and systolic dysfunction was higher in the symptomatic
      group. CONCLUSION: Considerable number of patients with DCAS have abnormal
      vascular load, abnormal LV function, and significant coexisting disorders. These
      could influence the total pathophysiologic burden on the heart and symptom
      expression. Thus, DCAS should not be considered just as valvular stenosis, but a
      syndrome of DCAS because of the diagnostic, prognostic, and therapeutic
      implications of various factors associated with it.

PMID- 22963401
TI  - Towards a defined, serum- and feeder-free culture of stratified human oral
      mucosal epithelium for ocular surface reconstruction.
AB  - PURPOSE: Ocular surface reconstruction with cultivated oral mucosal epithelial
      transplantation technique is a viable treatment option for severe ocular surface
      injuries and diseases with limbal stem cell deficiency. Currently, this technique
      is based on utilization of xenogenic, allogenic or undefined components such as
      murine 3T3 feeders, serum and amniotic membrane. In this study, we aimed to find
      a more defined culture method to generate stratified human oral mucosal
      epithelium. METHODS: In this study, we have examined the formation of stratified
      cell sheets from human oral mucosal epithelial cells under serum-free culture
      environment both in the absence and presence of fibroblast-conditioned culture
      medium and elevated epidermal growth factor (EGF) concentration. RESULTS: In all
      examined culture conditions, the cultivated oral epithelial cells formed a
      stratified tissue, which was positive for keratins K3/12, K4 and K13. The tissue
      engineered oral epithelia also expressed proliferation and progenitor markers
      Ki67 and p63 in the basal layer of the cell sheets, suggesting that the epithelia
      still had regenerative capacity. The cultures presented expression of tight
      junction proteins ZO-1 and occludin and high transepithelial electrical
      resistance values. CONCLUSION: In this culture method, we have been able to
      produce stratified cell sheets successfully without serum, conditioning of the
      medium or increased EGF concentration. We provide a novel protocol to produce
      tight multi-layered epithelium with proliferative potential, which can be easily
      adapted for cultivated oral mucosal epithelial transplantation.

PMID- 22963400
TI  - Differential effects of arsenic trioxide on chemosensitization in human hepatic
      tumor and stellate cell lines.
AB  - BACKGROUND: Crosstalk between malignant hepatocytes and the surrounding
      peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic
      resistance. To examine the chemotherapy resistance of these two cellular
      compartments in vitro, we evaluated a well-established hepatic tumor cell line,
      HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the
      chemosensitization potential of arsenic trioxide (ATO) in combination with
      sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells.
      METHODS: Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination
      against HepG2 cells and LX2 cells was measured by an automated high throughput
      cell-based proliferation assay. Changes in survival and apoptotic signaling
      pathways were analyzed by flow cytometry and western blot. Gene expression of the
      5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR.
      RESULTS: Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib
      and ATO at 24 hr (ATO IC(50): 5.3 MUM in LX2; 32.7 MUM in HepG2; Sorafenib
      IC(50): 11.8 MUM in LX2; 9.9 MUM in HepG2). In contrast, 5-FU cytotoxicity
      required higher concentrations and prolonged (48-72 hr) drug exposure. Concurrent
      ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased
      cytotoxicity due in part to modulation of thymidylate synthase levels by ATO.
      Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2
      cytotoxicity, possibly due to a significant decrease in MAPK activation in
      comparison to treatment with ATO alone. CONCLUSIONS: ATO differentially
      sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and
      sorafenib. Given the importance of both of these cell types in
      hepatocarcinogenesis, these data have implications for the rational development
      of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma
      (HCC).

PMID- 22963402
TI  - Melicilamide A: a new ceramide from Milicia excelsa.
AB  - This article deals with a phytochemical investigation of Melicia excelsa from
      which melicilamide A (1), a new ceramide has been isolated. Its structure was
      determined by comprehensive analyses of its (1)H- and (13)C-NMR, COSY, HMQC and
      HMBC spectroscopic, EI-MS and ESI-MS data. The remaining one known compound was
      identified as beta-sitosterol glucopyranoside. 

PMID- 22963403
TI  - Impact of live-donor exchange on transplant waiting time.

PMID- 22963404
TI  - Binder-free and carbon-free nanoparticle batteries: a method for nanoparticle
      electrodes without polymeric binders or carbon black.
AB  - In this work, we have developed a new fabrication method for nanoparticle (NP)
      assemblies for Li-ion battery electrodes that require no additional support or
      conductive materials such as polymeric binders or carbon black. By eliminating
      these additives, we are able to improve the battery capacity/weight ratio. The NP
      film is formed by using electrophoretic deposition (EPD) of colloidally
      synthesized, monodisperse cobalt NPs that are transformed through the nanoscale
      Kirkendall effect into hollow Co(3)O(4). EPD forms a network of NPs that are
      mechanically very robust and electrically connected, enabling them to act as the
      Li-ion battery anode. The morphology change through cycles indicates stable 5-10
      nm NPs form after the first lithiation remained throughout the cycling process.
      This NP-film battery made without binders and conductive additives shows high
      gravimetric (>830 mAh/g) and volumetric capacities (>2100 mAh/cm(3)) even after
      50 cycles. Because similar films made from drop-casting do not perform well under
      equal conditions, EPD is seen as the critical step to create good contacts
      between the particles and electrodes resulting in this significant improvement in
      battery electrode assembly. This is a promising system for colloidal
      nanoparticles and a template for investigating the mechanism of lithiation and
      delithiation of NPs.

PMID- 22963405
TI  - Working memory load moderates late attentional bias in social anxiety.
AB  - The vigilance-avoidance hypothesis suggests that socially anxious individuals
      attempt to detect signs that they are being evaluated (vigilance) and
      subsequently direct attention away from such stimuli (avoidance). Although
      extensive evidence supports vigilance, data concerning subsequent avoidance is
      equivocal. Drawing from models of attention, the current study hypothesised that
      working memory load moderates late attentional bias in social anxiety such that
      avoidance occurs if working memory load is low, and difficulty disengaging
      attention occurs if working memory load is high. Forty-one undergraduates (19
      socially anxious; 22 non-anxious controls) completed a dot-probe task with
      emotional (happy and disgust) and neutral facial expressions and a concurrent n
      back task. Results supported the hypothesis such that socially anxious subjects
      demonstrated avoidance of disgust faces when working memory load was absent, but
      had difficulty disengaging attention during high working memory load. Theoretical
      implications and directions for future research are discussed.

PMID- 22963406
TI  - Tyrosine-containing peptides are precursors of tyramine produced by Lactobacillus
      plantarum strain IR BL0076 isolated from wine.
AB  - BACKGROUND: Biogenic amines are molecules with allergenic properties. They are
      found in fermented products and are synthesized by lactic acid bacteria through
      the decarboxylation of amino acids present in the food matrix. The concentration
      of biogenic amines in fermented foodstuffs is influenced by many environmental
      factors, and in particular, biogenic amine accumulation depends on the quantity
      of available precursors. Enological practices which lead to an enrichment in
      nitrogen compounds therefore favor biogenic amine production in wine. Free amino
      acids are the only known precursors for the synthesis of biogenic amines, and no
      direct link has previously been demonstrated between the use of peptides by
      lactic acid bacteria and biogenic amine synthesis. RESULTS: Here we demonstrate
      for the first time that a Lactobacillus plantarum strain isolated from a red wine
      can produce the biogenic amine tyramine from peptides containing tyrosine. In our
      conditions, most of the tyramine was produced during the late exponential growth
      phase, coinciding with the expression of the tyrDC and tyrP genes. The DNA
      sequences of tyrDC and tyrP in this strain share 98% identity with those in
      Lactobacillus brevis consistent with horizontal gene transfer from L. brevis to
      L. plantarum. CONCLUSION: Peptides amino acids are precursors of biogenic amines
      for Lactobacillus plantarum strain IR BL0076.

PMID- 22963407
TI  - Size-resolved particle number emission patterns under real-world driving
      conditions using positive matrix factorization.
AB  - A novel on-board system was tested to characterize size-resolved particle number
      emission patterns under real-world driving conditions, running in a EURO4 diesel
      vehicle and in a typical urban circuit in Madrid (Spain). Emission profiles were
      determined as a function of driving conditions. Source apportionment by Positive
      Matrix Factorization (PMF) was carried out to interpret the real-world driving
      conditions. Three emission patterns were identified: (F1) cruise conditions, with
      medium-high speeds, contributing in this circuit with 60% of total particle
      number and a particle size distribution dominated by particles >52 nm and around
      60 nm; (F2) transient conditions, stop-and-go conditions at medium-high speed,
      contributing with 25% of the particle number and mainly emitting particles in the
      nucleation mode; and (F3) creep-idle conditions, representing traffic congestion
      and frequent idling periods, contributing with 14% to the total particle number
      and with particles in the nucleation mode (<29.4 nm) and around 98 nm. We suggest
      potential approaches to reduce particle number emissions depending on particle
      size and driving conditions. Differences between real-world emission patterns and
      regulatory cycles (NEDC) are also presented, which evidence that detecting
      particle number emissions <40 nm is only possible under real-world driving
      conditions.

PMID- 22963408
TI  - Extensive exometabolome analysis reveals extended overflow metabolism in various
      microorganisms.
AB  - Overflow metabolism is well known for yeast, bacteria and mammalian cells. It
      typically occurs under glucose excess conditions and is characterized by
      excretions of by-products such as ethanol, acetate or lactate. This phenomenon,
      also denoted the short-term Crabtree effect, has been extensively studied over
      the past few decades, however, its basic regulatory mechanism and functional role
      in metabolism is still unknown. Here we present a comprehensive quantitative and
      time-dependent analysis of the exometabolome of Escherichia coli, Corynebacterium
      glutamicum, Bacillus licheniformis, and Saccharomyces cerevisiae during well
      controlled bioreactor cultivations. Most surprisingly, in all cases a great
      diversity of central metabolic intermediates and amino acids is found in the
      culture medium with extracellular concentrations varying in the micromolar range.
      Different hypotheses for these observations are formulated and experimentally
      tested. As a result, the intermediates in the culture medium during batch growth
      must originate from passive or active transportation due to a new phenomenon
      termed "extended" overflow metabolism. Moreover, we provide broad evidence that
      this could be a common feature of all microorganism species when cultivated under
      conditions of carbon excess and non-inhibited carbon uptake. In turn, this
      finding has consequences for metabolite balancing and, particularly, for
      intracellular metabolite quantification and (13)C-metabolic flux analysis.

PMID- 22963409
TI  - Intra-day and inter-day reliability of heart rate variability measurement.
AB  - At present, analysis of heart rate variability (HRV) is becoming widely used as a
      clinical or research tool. Supported reliability studies for HRV measurement are,
      however, still limited. The main purpose was to perform an assessment of the
      absolute and relative reliability of HRV parameters from short-term recordings by
      means of orthoclinostatic stimulation and to investigate, whether there is a
      difference in repeating the retest immediately or after several days. The study
      group consisted of 99 participants (mean age 22 +/- 1.24 years). Standard HRV
      indexes were computed: PT (total spectral power), PHF (high frequency spectral
      power), PLF (low frequency spectral power) and LF/HF. Absolute reliability was
      assessed by the standard error of measurement and 95% limits of agreement;
      relative reliability was assessed by the intraclass correlation coefficient.
      There was also an estimate of the sample size needed to detect the mean
      difference >= 30% of the between-subject standard deviation. In conclusion, a
      large random variation (within individuals) of HRV parameters was revealed,
      regardless of whether the retest was repeated immediately or with an
      interruption. For most HRV parameters (particularly in the immediately repeated
      test-retest), however, random variation represents a limited portion of the
      between-subject variability.

PMID- 22963410
TI  - Scalp hair loss after transsphenoidal adenomectomy in patients with acromegaly.
AB  - OBJECTIVE: Scalp hair loss is often encountered in clinical practice in Japan
      after successful surgery for acromegaly. However, this intriguing issue has not
      been addressed in the literature. The aim of this study was to examine scalp hair
      loss after surgery for acromegaly. METHODS: Postoperative scalp hair loss was
      surveyed using a mail-back questionnaire given to 511 patients undergoing primary
      surgery for acromegaly, 484 of whom constitute the patient pool in this study.
      RESULTS: Of the 484 patients, 263 (54%) patients noticed varying degrees of hair
      loss between 3 and 6 months after surgery [the degree of alopecia was minimal in
      50 patients (10%), moderate in 117 patients (24%), and severe in 96 patients
      (20%)], although postoperative hair loss was noticed only in six (3.6%) of 167
      patients with nonfunctioning adenomas. Postoperative hair loss was significantly
      more common in female patients, cured patients and patients with severe
      postoperative growth hormone deficiency. Among those 263 patients, full recovery
      was reported by 85 patients (32%), incomplete recovery by 88 patients (34%), and
      hardly any recovery by 90 patients (34%). A lack of hair recovery was
      significantly more common in male patients or in patients with severe hair loss
      after surgery. CONCLUSIONS: This, the first large-scale, single-centre, clinical
      study to shed light on the issue of postoperative hair loss after surgery for
      acromegaly, shows that it is important to prospectively inform patients that
      varying degrees of hair loss occur in a large number of acromegalic patients,
      especially after successful surgery.

PMID- 22963411
TI  - Anti-VEGF therapy for the treatment of glaucoma: a focus on ranibizumab and
      bevacizumab.
AB  - INTRODUCTION: Anti-VEGF therapy has been widely used in the treatment of ocular
      neovascular diseases. Because of their anti-angiogenic and anti-fibrotic
      properties, anti-VEGF antibodies such as bevacizumab and ranibizumab have emerged
      as an adjunctive treatment modality in glaucoma to improve success of
      conventional treatments. AREAS COVERED: Ranibizumab is an anti-VEGF-A antigen
      binding fragment currently indicated in neovascular age-related macular
      degeneration as well as macular edema following retinal vein occlusion. Several
      off-label uses include the treatment of neovascular glaucoma to regress/suppress
      iris and iridocorneal angle neovascularization and the modulation of wound
      healing after glaucoma filtration surgery. Bevacizumab is a full-length anti-VEGF
      antibody, which is also being used in aforementioned eye conditions off-label. An
      overview of these anti-VEGF antibodies and the results of preclinical and
      clinical studies regarding their use in the treatment of glaucoma are presented.
      EXPERT OPINION: Early studies on the utility of both bevacizumab and ranibizumab
      in neovascular glaucoma and filtration surgery reported promising results.
      However, a large-scale randomized clinical trial as well as comparative studies
      between the two anti-VEGF antibodies are currently lacking. A single dose of
      ranibizumab costs approximately 40 times as much as a single dose of bevacizumab.
      Clinicians should take this into account, in addition to their differences in the
      efficacy and safety, when treating patients.

PMID- 22963412
TI  - Telocytes in the urinary system.
AB  - BACKGROUND: Telocytes, a new type of interstitial cells, have been identified in
      many organs in mammals. The present studies aimed at investigating the
      ultrastructure, distribution and interactions of telocytes with surrounding cells
      in the urinary system of rats, to confirm the existence of telocytes in kidneys,
      ureter and urinary bladder. METHODS: Samples of kidney, ureter, or urinary
      bladder were harvested for the ultrastructure by the electron microscope. The
      primary culture of telocytes was performed to investigate the dynamic
      alterations. RESULTS: Telocytes mainly located in the sub-capsular space of
      kidney, or between smooth muscle bundles and in the lamina propria of ureter and
      urinary bladder. Telocytes established numerous contacts with macrophages in the
      sub-capsular space of kidney, or with smooth muscle cells, nerve endings as well
      as blood capillaries in the ureter and urinary bladder. The complete morphology
      of telocytes with telopodes was observed clearly through the primary cell culture
      from the kidney tissues of rats. CONCLUSIONS: Our data evidenced the existence of
      telocytes in the urinary system, which may contribute to the tissue reparation
      and regeneration.

PMID- 22963414
TI  - Howard H. Kendler (1919-2011).
AB  - Presents an obituary for Howard H. Kendler. Kendler was born in New York City on
      June 9, 1919, and died in Santa Barbara, California, on February 17, 2011.
      Kendler majored in psychology at Brooklyn College, where he was an assistant to
      Abraham Maslow, the father of humanistic psychology, and did a research project
      on the psychology of thinking under the supervision of Solomon Asch, a leading
      Gestalt psychologist. Howard Kendler's career was characterized by insightful
      experiments and a consistent analysis of the fundamental issues of the nature of
      our science, its methods, and its role in the community. The breadth of his
      knowledge and the depth of his thinking on these issues are rare. Although he did
      not settle these issues, he brought them into clear focus and forcefully
      advocated for his point of view. He was a visiting professor at the University of
      California, Berkeley, Hebrew University in Jerusalem, and Tel-Aviv University and
      was a fellow at the Center for Advanced Study in the Behavioral Sciences. He held
      the offices of president of the Western Psychological Association, chairman of
      the Board of Governors of the Psychonomic Society, and president of the Division
      of General Psychology and the Division of Experimental Psychology of the American
      Psychological Association.

PMID- 22963415
TI  - Ulric Neisser (1928-2012).
AB  - Presents an obituary for Ulric Neisser. Neisser changed the course of psychology.
      He moved a generation of psychologists in the direction of the field named by his
      first book, Cognitive Psychology (1967, Appleton-Century-Crofts). He then
      challenged that field with his later book Cognition and Reality (1976, W. H.
      Freeman). Finally, he explored cracks in the received wisdom within the fields of
      attention, memory, and intelligence through a distinguished array of edited
      volumes and provocative articles. Throughout his life, he made a marriage between
      belief in discovered truth and complete skepticism by means of a passionate,
      serial monogamy of ideas. He died on February 17, 2012, at age 83 of
      complications from Parkinson's disease. His many honors included election as a
      member of the National Academy of Sciences and as a fellow of the American
      Academy of Arts and Sciences.

PMID- 22963416
TI  - Albert H. Hastorf III (1921-2011).
AB  - Presents an obituary for Albert H. Hastorf III. Albert H. Hastorf III, a pioneer
      in the study of social perception and interaction and a celebrated member of the
      Stanford University administration, died September 26, 2011, in Palo Alto,
      California. Al was known early in his career as the coauthor of one of social
      psychology's most famous studies-a study that vividly illustrated the
      constructive and potentially biased nature of perception-and his contributions to
      psychology and American academia were wide-ranging. Hastorf joined Stanford's
      faculty in 1961, serving as executive head of the Psychology Department from 1961
      to 1970. He was also a founder of the university's Interdisciplinary Human
      Biology Program, soon one of Stanford's most popular majors and an attractive
      gateway for students interested in medicine. Al's unique gifts as an
      administrator were apparent to all who knew him. His sound judgment, personal
      graciousness, good humor, and unquestioned integrity made him a popular choice as
      dean of the School of Humanities & Sciences from 1970 to 1974 and as provost from
      1980 to 1984. The esteem in which Al was held by the Stanford community was
      recognized with a succession of awards, including the Lloyd W. Dinkelspiel Award
      for Outstanding Service to Undergraduate Education and the Richard W. Lyman Award
      for unique and dedicated service to the university.

PMID- 22963417
TI  - Herbert M. Lefcourt (1936-2011).
AB  - Presents an obituary for Herbert M. Lefcourt. In the summer of 1963, with a
      freshly minted PhD degree in his hands, Lefcourt moved to Waterloo, Ontario,
      Canada. Along with several other young faculty members from the United States,
      Herb had been recruited to help establish a new PhD program in clinical
      psychology at the University of Waterloo. Over the ensuing years, it became
      recognized as one of the leading clinical programs in North America. Ever an
      optimist with a zest for life, Herb focused on the positive side of human nature
      in his research interests. While others studied stress and distress, Herb was
      more interested in the personality traits of people who are particularly
      resilient, able to withstand adversity without succumbing to illness and
      depression. Later in his career, his interests turned to the study of the sense
      of humor, again conceptualized as a personality variable with important
      implications for mental and physical health. Herb retired from the university in
      1996 and was awarded the honorific of Distinguished Professor Emeritus. He had a
      very enjoyable retirement, pursuing his many interests, which included
      international travel, hiking, woodworking, literature, film, and classical music,
      and enjoying his summer cottage on Manitoulin Island in Lake Huron. He is
      remembered as an energetic teacher who, in addition to having an eclectic command
      of the theory and research, drew on his vast knowledge of literature, film, and
      current events to make his lectures interesting, informative, and thought
      provoking.

PMID- 22963418
TI  - Jeri Altneu Sechzer (1926-2011).
AB  - Presents an obituary for Jeri Altneu Sechzer. Jeri studied at the University of
      Pennsylvania, where her mentor was the renowned physiological psychologist Elliot
      Stellar. She received her doctorate in 1962 with a specialty in physiological
      psychology. That same year she was elected to Sigma Xi, the scientific research
      society, and received the Creative Talent Award from the American Institute of
      Research for her doctoral dissertation. She completed a U.S. Public Health
      Service Postdoctoral Fellowship at the University of Pennsylvania School of
      Medicine, after which she accepted a position at Baylor University College,
      followed by a position at the New York Hospital-Cornell University Medical
      Center. She completed her career as a visiting professor in the Psychology
      Department at Pace University. Jeri's husband of 56 years, Philip, died in 2004.
      As a result of her experience looking after him during the long illness that
      preceded his death, she became interested in the psychological impact of the
      stresses that caregivers face. She was planning to organize a conference on this
      subject when she suffered her final illness, leading to her death on October 29,
      2011, just before her 85th birthday.

PMID- 22963419
TI  - James Hillman (1926-2011).
AB  - Presents an obituary for James Hillman. James Hillman, the third child of
      Madeline and Julian Hillman, died of metastatic bone cancer at his home in
      Thompson, Connecticut, on October 27, 2011. The parent of "archetypal
      psychology," he was born on April 12, 1926, at the Breakers, a then-opulent hotel
      founded by his family that overlooked the boardwalk and beach in Atlantic City,
      New Jersey. With an extensive footing in the classics and classical humanism, Jim
      established the foundations for his emerging archetypal psychology. With
      archetypal psychology, he was to move away from a dependence on the concept of a
      personal ego in favor of larger sources that relied on his notion of variegated
      identity. He proposed a profusion of mythical images that emerge under the rubric
      of "soul." Soul stands as an appellation indicating a deepening of psychic
      events, such as when dreams, chaos, and "pathologizing" (the struggles of
      imagination) are most experienced. For Hillman, psychology could not be taken as
      a separate discipline isolated from mythology, literature, art, philosophy,
      politics, religion, natural science, and the ordinary affairs of individuals.
      Hillman envisioned archetypes as processes that bear evidence to personal
      suffering and, in so doing, prompt the expansion of compassion. In 1975, Jim was
      nominated for a Pulitzer Prize for his book Re-Visioning Psychology (Harper &
      Row). In addition to many other citations, Jim had the high honor in 2001 of
      receiving the Medal of the Presidency of the Italian Republic.

PMID- 22963420
TI  - John M. Neale (1943-2011).
AB  - Presents an obituary for John M. Neale. Neale died in Hilton Head, South
      Carolina, on November 19, 2011, after a long illness. He was born on August 31,
      1943, in Toronto, Canada. He received his bachelor's degree from the University
      of Toronto in 1965, where his interest in psychology had been sparked by an
      introductory course taught by George Mandler. After working at a residential
      treatment center for emotionally disturbed children, he decided to pursue
      graduate training in clinical psychology and enrolled at Vanderbilt University.
      Rue Cromwell served as John's mentor and stimulated his interest in the
      investigation of perception and cognition in schizophrenia. His doctorate was
      awarded in 1969, after completion of his internship at the Langley Porter
      Neuropsychiatric Institute in San Francisco. John was hired in 1969 as an
      assistant professor in the new and exciting psychology department (founded in
      1965) at the State University of New York at Stony Brook. That department
      remained his academic home for his entire career. Outside of his academic
      pursuits, John was an avid New York Giants fan, an extensive traveler, an
      excellent skier and tennis player, a music lover and jukebox collector, an
      outstanding cook, a terrific dancer, and a devoted dog owner. He continued to
      pursue these interests throughout his life, taking cooking classes, traveling to
      exotic locales with his wife Gail, and, when his health precluded more rigorous
      athletic pursuits, faithfully walking and playing with his dogs.

PMID- 22963421
TI  - An alternative to thought suppression?
AB  - Comments on the original article, "Setting free the bears: Escape from thought
      suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed
      that we might have to learn to live with bad thoughts, the present author
      discusses the use of imagination and guided imagery as an alternative to forced
      thought suppression.

PMID- 22963422
TI  - Knowing what we do not know about sexual orientation change efforts.
AB  - Comments on the original article, "Guidelines for psychological practice with
      lesbian, gay, and bisexual clients," by the American Psychological Association
      (see record 2011-19419-001). The present authors notes that the APA has provided
      a very helpful document for those who do clinical work with individuals
      experiencing same-sex attractions. Psychologists no doubt need to be familiar
      with the literature described in these guidelines as a part of ethical practice.
      However, the present authors register concern regarding how the guidelines
      address sexual orientation change efforts (SOCE). They focus their critique on
      how the guidelines portray two issues pertaining to SOCE-effectiveness and harm
      and conclude with a proposal to move the discussion forward via science.

PMID- 22963423
TI  - Science meets practice in determining effectiveness of sexual orientation change
      efforts.
AB  - Comments on the original article, "Guidelines for psychological practice with
      lesbian, gay, and bisexual clients," by the American Psychological Association
      (see record 2011-19419-001). Guideline 3 of the acknowledges the diversity of
      human sexual orientation and that "efforts to change sexual orientation have not
      been shown to be effective or safe" (p. 14). As noted in the Report of the
      American Psychological Association Task Force on Appropriate Therapeutic
      Responses to Sexual Orientation (APA, 2009), "Current criteria for effective
      treatments and interventions are specific in stating that to be considered
      effective, an intervention has consistent positive effects without serious
      harmful side effects [emphasis added]" (p. 26). The present authors note that
      half a century of scientific research on a variety of sexual orientation change
      efforts (SOCE) has not demonstrated their effectiveness according to the criteria
      of consistent positive effects and absence of serious harmful effects. Guideline
      3 (APA, 2012) therefore urges psychologists to closely assess the motivations of
      clients who seek SOCE in the context of stigma and internalized prejudice about
      their non-heterosexual orientation. In addition, the guideline also recommends
      that psychologists obtain truthful, thorough, and thoughtful informed consent and
      that they focus on personal integration instead of sexual orientation change. The
      burden of proof has been on advocates of SOCE, and the present authors assert
      that it has not been met.

PMID- 22963424
TI  - No narrowing in mean Black-White IQ differences--predicted by heritable g.
AB  - Comments on the original article, "Intelligence: New findings and theoretical
      developments," by R. E. Nisbett, J. Aronson, C. Blair, W. Dickens, J. Flynn, D.
      F. Halpern, and E. Turkheimer (see record 2011-30298-001). The present authors
      assert Nisbett et al were incorrect when they claimed that between 1972 and 2002
      there was a 5.5-point narrowing of the 15-point IQ gap between Blacks and Whites
      (p. 146). In doing so, they sidestepped Rushton and Jensen's (2006) objections to
      Dickens and Flynn's (2006) evidence and failed to include subsequent evidence.
      The present authors maintain that Nisbett et al failed to describe accurately how
      heritable g provides evidence of a significant genetic contribution to Black
      White differences. The present authors claim Nisbett et al obscured the topic by
      invoking alleged age and social class interactions and adoption studies of very
      young children. Many twin and adoption studies have shown that by adolescence,
      there are equal heritabilities (about 50%) for Whites, Blacks, and East Asians
      (Hur, Shin, Jeong, & Han, 2006; Rushton & Jensen, 2010b). There is no evidence of
      any special cultural influence, such as extreme deprivation or being raised as a
      visible minority, that operates in one group and not in others.

PMID- 22963425
TI  - Ability differentials between nations are unlikely to disappear.
AB  - Comments on the original article, "Intelligence: New findings and theoretical
      developments," by R. E. Nisbett, J. Aronson, C. Blair, W. Dickens, J. Flynn, D.
      F. Halpern, and E. Turkheimer (see record 2011-30298-001). This comment
      challenges Nisbett et al's argument that Flynn effect gains will eliminate cross
      national IQ inequalities "by the end of the 21st century and falsify the
      hypothesis that some nations lack the intelligence to fully industrialize" (p.
      140). The present authors find that this optimism is not justified by the
      evidence. In Europe and the United States, Flynn effects are indeed rare in
      cohorts born after about 1980. Furthermore, it is necessary to distinguish
      between accelerated childhood development and higher adult intelligence.

PMID- 22963426
TI  - The growing significance of hot intelligences.
AB  - Comments on the original article, "Intelligence: New findings and theoretical
      developments," by R. E. Nisbett, J. Aronson, C. Blair, W. Dickens, J. Flynn, D.
      F. Halpern, and E. Turkheimer (see record 2011-30298-001). The present authors
      note that Nisbett et al's review focuses on intelligences that have been topics
      of research through the 20th century. Since then, however, attention to a new
      group of intelligences that the present authors refer to as "hot intelligences"
      has been growing (Mayer, Salovey, & Caruso, 2004). Although Nisbett et al (2012)
      mentioned potential newcomers to the group of intelligences, such as practical
      intelligence, the present authors feel that future reviews should consider the
      burgeoning research in new conceptions of intelligence. Here the authors express
      a rationale for including a consideration of these newly described intelligences.

PMID- 22963427
TI  - Group differences in IQ are best understood as environmental in origin.
AB  - Responds to the comments by J. P. Rushton (see record 2012-24333-012); M. A.
      Woodley and G. Meisenberg (see record 2012-24333-013); and J. D. Mayer, D. R.
      Caruso, A. T. Panter, and P. Salovey (see record 2012-24333-014) on the present
      authors' original article, "Intelligence: New findings and theoretical
      developments" (see record 2011-30298-001). Here, the authors address the concerns
      raised by Rushton and by Woodley and Meisenberg, and conclude by agreeing with
      Mayer et al's claim that many types of abilities can be thought of as
      intelligence of a kind. They note, however, that it has proved hard to show that
      measures of emotional intelligence or social intelligence contribute to behavior
      we would want to call intelligent over and above their correlation with
      conventional IQ tests.

PMID- 22963428
TI  - Quantifying the cost of laparoscopic inguinal hernia repair.
AB  - BACKGROUND: Laparoscopic inguinal hernia repair has been widely adopted. While
      the clinical advantages and disadvantages are well-quantified, the economic cost
      is less well-studied. METHODS: A retrospective audit and case review of a single
      centre public hospital consecutive case series was performed using data captured
      from real-time stock usage tracking technology and review of electronic medical
      records. RESULTS: Laparoscopic inguinal hernia repair requires 11-min (21%) extra
      theatre time and costs $1268 (370%) more for single-use disposable equipment and
      prostheses. CONCLUSIONS: Laparoscopic inguinal hernia repair does not require
      significantly more theatre time, but has a higher short-term in-hospital cost.
      Repair technique should be tailored according to patient factors.

PMID- 22963429
TI  - T(reg) cells may regulate interlukin-17 production by modulating TH1 responses in
      1,3-beta-glucan-induced lung inflammation in mice.
AB  - 1,3-beta-glucan is considered a fungal biomarker and exposure to this agent can
      induce lung inflammation. Complement activation plays an important role in early
      immune responses to beta-glucan. Previous studies showed that T-regulatory cells
      (Tregs) regulated 1,3-beta-glucan-induced lung inflammation by modulating the
      maintenance of immune homeostasis in the lung. Both interleukin (IL)-17 and TH17
      cells play pivotal roles in inflammation associated with lung disease and share
      reciprocal developmental pathways with Tregs. However, the effect of Tregs on IL
      17 and TH17 responses in 1,3-beta-glucan-induced lung inflammation remains
      unclear. In this study, mice were exposed to 1,3-beta-glucan by intratracheal
      instillation. To investigate the effects of Tregs on IL-17 and TH17 cells in the
      induced lung inflammation, a Treg-depleted mice model was generated by
      administration of anti-CD25 mAb. The results indicated that Treg-depleted mice
      showed more severe pathological inflammatory changes in lung tissues. Tregs
      depletion reduced IL-17 expression in these tissues, and increased those of TH1
      cytokines. The expression of IL-17 increased at the early phase of the
      inflammation response. There were no significant effects of the Tregs on
      expression of RORgammat and IL-6 or the amount of CD4(+)IL-17(+) cells in the
      lungs. When taken together, the late phase of the 1,3-beta-glucan-induced
      inflammatory response in the mice was primarily mediated by TH1 cytokines rather
      than IL-17. In contrast, the early phase of the inflammatory response might be
      mediated in part by IL-17 along with activated complement. Tregs might be
      required for IL-17 expression during the late phase inflammatory response in
      mice. The increased IL-17 mRNA observed during the 1,3-beta-glucan induced
      inflammatory response were attributed to cells other than TH17 cells. 

PMID- 22963430
TI  - Increased numbers of P63-positive/CD117-positive cells in advanced adenoid cystic
      carcinoma give a poorer prognosis.
AB  - OBJECTIVES: This study consisted of two parts. One part was to analyze the
      survival rates of adenoid cystic carcinoma (ACC) in Chinese and explain the
      difference between our data and the literature. The other was to analyze the
      relationship between the expression of CD117 and the histological grade and the
      prognosis. METHODS: A retrospective study of 80 ACC patients was performed.
      Clinical data were collected, and p63, CD117 were detected by immunohistochemical
      staining. RESULTS: Eighty patients received follow-ups 3 to 216 months after
      initial diagnosis. ACC occurred in the lacrimal gland (26.3%, n = 21), nasal
      cavity and parasinus (33.8%, n = 27) and other sites (40.0%, n = 33). The 5-year
      and 10-year survival rates were 66.41% and 10.16%, respectively. Over expression
      of CD117 was detected in p63-negative cells in 94.3% of cases and in p63-positive
      cells in 45.8%. The expression of CD117 in p63-positive cells was significantly
      associated with the histological grade (P<0.001) and prognosis (P = 0.037) in
      patients in the advanced stage. CONCLUSIONS: ACC had a good 5-year survival but
      poor 10-year survival in Chinese, which differed from the occidental data. More
      p63+/CD117+ cells were associated with a higher histological grade and poorer
      outcome. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1701457278762097.

PMID- 22963431
TI  - Measured versus simulated dietary pesticide intakes in children.
AB  - Children's dietary pesticide intakes can be measured directly through duplicate
      diet samples, but instead are frequently estimated using national residue data.
      We compared organophosphorus and pyrethroid pesticide intakes from conventional
      fruit, fruit juices and vegetables measured for two cohorts of children aged 3-11
      years in the Children's Pesticide Exposure Study (CPES) with corresponding
      intakes simulated using CPES consumption and body weight data and residue data
      from the US Pesticide Data Program (PDP). We calculated daily measured pesticide
      intakes by multiplying grams eaten with measured concentrations and dividing by
      body weight. For the simulated intakes we combined the CPES consumption and PDP
      residue data, randomly sampling the PDP data 500 times in order to create
      distributions of daily intakes for each cohort, including 95% uncertainty
      intervals for each percentile. In all cases, the measured medians fell below the
      lower uncertainty bounds of the simulated medians, reflecting the lower detection
      limits of CPES versus PDP and the high number of non-detects in each. Upper
      percentile measured intakes were generally lower as well, except for higher
      measured intakes of phosalone from watermelon. This work shows that using PDP
      data could generate probabilistic estimates of dietary pesticide intakes that do
      not differ appreciably from measured intakes except in some cases.

PMID- 22963433
TI  - Pharmacology and therapeutic activity of purinergic drugs for disorders of the
      nervous system.

PMID- 22963432
TI  - Transmission dynamics of ESBL-producing Escherichia coli clones in rehabilitation
      wards at a tertiary care centre.
AB  - Increasing resistance due to the production of ESBL in Escherichia coli (ESBL-E.
      coli) has become a major threat to public health. Our aims were to study the
      incidence of ESBL-E. coli acquisition during hospitalization and the transmission
      rates of different ESBL-E. coli clones. This was a prospective case-control
      study, conducted in two geriatric rehabilitation wards in Tel-Aviv. Serial rectal
      cultures were collected from admission till discharge. All patient-unique ESBL-E.
      coli isolates were subjected to molecular typing by PFGE, MLST and determination
      of ESBL genes. An acquisition of ESBL-E. coli was defined as traceable when a
      patient with the same ST, PFGE type and ESBL gene was hospitalized in the same
      ward in parallel to the acquisition case. ESBL-E. colis were recovered from 125
      patients out of 492 enrolled: 52 were recovered upon admission, 59 acquired ESBL
      E. coli during their stay, and there was undetermined status in 14 patients. A
      low Norton's score was associated with acquisition (O.R. 1.14 for each point, 95%
      C.I. 1.01-1.29, p < 0.05). ESBL-E. coli infections (n = 9) had occurred only in
      ESBL-E. coli carriers. The pandemic ST131 clone was the most common (48/125). The
      majority of the isolates (101/125) produced CTX-M-type ESBL. Of the 59
      acquisition cases, 32 were traced to another patient. In-hospital dissemination
      was highest in the CTX-M-27-producing ST131 and the SHV-5-producing ST372 sub
      clones (acquisition/admission ratios of 17/11 and 9/3, respectively), with almost
      all cases traced to other patients. In conclusion, most ESBL-E. coli acquisition
      cases were traceable to other patients. The transmission potential varied
      significantly between ESBL-E. coli clones.

PMID- 22963434
TI  - Regulation of P2X3 receptor structure and function.
AB  - The strong expression of ATP-gated P2X3 receptors by a subpopulation of sensory
      neurons indicates the important role of these membrane proteins in nociceptive
      signaling in health and disease, especially when the latter is accompanied by
      chronic pain syndromes. Molecular and cell biology studies have shown that these
      receptors exist mainly as trimeric homomers, and, in part, as heteromers
      (assembly of two P2X3 subunits with one P2X2). Recent investigations have
      suggested distinct molecular determinants responsible for agonist binding and
      channel opening for transmembrane flux of sodium, calcium and potassium ions.
      Trimeric P2X3 receptors are rapidly activated by ATP and can be strongly
      desensitized in the continuous presence of the agonist. Thus, the factors
      controlling the degree of desensitization and the time necessary to recover from
      it are essential elements to determine how efficiently and how often the P2X3
      receptor can signal pain. Endogenous substances, widely thought to be involved in
      triggering pain especially in pathological conditions, can potently modulate the
      expression and function of P2X3 receptors, with differential changes in response
      amplitude, desensitization and recovery. Hence, studying P2X3 receptors can lead
      not only to the design of novel antagonists as analgesics, but also to identify
      intracellular interactors that may be targeted to downregulate P2X3 receptors.
      Strong facilitation of P2X3 receptor function is induced by endogenous substances
      like the neuropeptide calcitonin gene-related peptide and the neurotrophins nerve
      growth factor and brain-derived neurotrophic factor. These substances possess
      distinct mechanisms of action on P2X3 receptors, generally attributable to
      discrete phosphorylation of N- or C-terminal P2X3 domains.

PMID- 22963435
TI  - P2X4 receptors of microglia in neuropathic pain.
AB  - We have learned various data on the role of purinoceptors (P2X4, P2X7, P2Y6 and
      P2Y12 receptors) expressed in spinal microglia and several factors that
      presumably activate microglia in neuropathic pain after peripheral nerve injury.
      Especially P2X4 receptors (P2X4Rs) make a critical contribution to the pain
      processing. P2X4Rs of microglia might be promising targets for treating
      neuropathic pain. A predicted therapeutic benefit of interfering with microglial
      P2X4Rs may be that normal pain sensitivity would be unaffected since expression
      or activity of most of these receptors are upregulated or enhanced predominantly
      in activated microglia in the spinal cord where damaged sensory fibers project.
      Recently, we found that CCL21 regulates the expression of P2X4Rs in different
      manners, respectively. These new findings also provide novel targets for
      developing anti-neuropathic pain medicines.

PMID- 22963436
TI  - Potential therapeutic relevance of adenosine A2B and A2A receptors in the central
      nervous system.
AB  - Adenosine A2B and, much more importantly, adenosine A2A receptors modulate many
      physiological and pathological processes in the brain. In this review, the most
      recent evidence concerning the role of such receptors and their potential
      therapeutic relevance is discussed. The low affinity of A2B receptors for
      adenosine implies that they might represent a good therapeutic target, since they
      are activated only under pathological conditions (when adenosine levels raise up
      to micromolar concentrations). The availability of selective ligands for A2B
      receptors would allow exploration of such an hypothesis. Since adenosine A2A
      receptors mediate both potentially neuroprotective and potentially neurotoxic
      effects, their role in neurodegenerative diseases is highly controversial.
      Nevertheless, A2A receptor antagonists have shown clear antiparkinsonian effects,
      and a great interest exists on the role of A2A receptors in Alzheimer's disease,
      brain ischaemia, spinal cord injury, drug addiction and other conditions. In
      order to establish whether such receptors represent a target for CNS diseases, at
      least two conditions are needed: the full comprehension of A2A-dependent
      mechanisms and the availability of ligands capable of discriminating among the
      different receptor populations.

PMID- 22963437
TI  - From A1 to A3 en passant through A(2A) receptors in the hippocampus:
      pharmacological implications.
AB  - The role of A1 and A3 receptors is discussed based on data almost exclusively
      obtained in the hippocampus. This brain area, where A1 receptor expression
      predominates, has been a matter of intensive research in the adenosine field.
      Interestingly, in the last decade, the relevance of the much less expressed
      adenosine receptor in the hippocampus, the A2A receptor, has been put forward.
      These two high affinity receptors operate as effective regulators of a number of
      neurotransmitters and/or neuromodulators, through modulation of their release,
      action, or even inactivation. Therefore, A1 and A2A receptors constitute a must
      in the discussion about adenosine receptors in the hippocampus, and consequently,
      about the potential implications of their pharmacological manipulation and drug
      targeting.

PMID- 22963438
TI  - P2X1 and P2X2 receptors in the central nervous system as possible drug targets.
AB  - P2X receptors are homo- or heterotrimeric ATP-gated cation channels that assemble
      from seven subunits, P2X1-P2X7. To our knowledge, no drug that acts on the P2X1
      or P2X2 receptors in the CNS or elsewhere in the body has been approved, nor is
      there such a drug currently in clinical trials. Only a few non-drug-like
      antagonists such as the suramin derivatives NF449 and NF770 and the anthraquinone
      derivative PSB-1011 are available as pharmacological tools to block the P2X1 and
      P2X2 receptors, respectively. The focus of this review is twofold. First, we
      review the current knowledge of the role of the P2X1 and P2X2 receptors in normal
      and pathological CNS functions as inferred from experiments with wild-type, P2X1
      knockout and P2X2 knockout mice. From the available data we conclude that the
      P2X1 and P2X2 receptors may have therapeutic potential as targets for
      neuroprotective drugs. Second, we review the impact of the recent resolution of
      the crystal structure of the zebrafish P2X4 receptor in the apo closed state and
      the ATP-bound open state. The P2X4 crystal structure opens the exciting
      possibility to generate P2X homology models for a rational drug design. In silico
      docking experiments with a homology-modeled rat P2X2 receptor revealed an almost
      perfect coordination of the nanomolar potent P2X2 antagonist NF770 through strong
      polar interactions between the acidic groups of NF770 and the mostly basic groups
      of the ATP-binding pocket. Such structural information might be helpful in
      designing drug-like compounds that function as selective P2X receptor antagonists
      without the pharmacokinetic limitations of the currently available antagonists.

PMID- 22963439
TI  - Purinergic signalling: what is missing and needed next? The use of transgenic
      mice, crystallographic analysis and MicroRNA.
AB  - While ATP is recognized as an intracellular energy source for many biochemical
      reactions, it is now recognised it is also an important extracellular signalling
      molecule. ATP is involved in both physiological and pathological events in most
      cell types, and receptor subtypes have been cloned and characterised. An
      important goal of purinergic research today is to annotate the human genome with
      functional information regarding the role of genes for purinergic receptors,
      ectonucleotidases and transporters, in brain physiology and pathology. Insights
      into these roles have been gained also from studies of the various purinergic
      knockouts, and here we report on the generation of these purinergic
      receptor/ectonucleotidase-null mice. Recent X-ray structures of purinergic ligand
      activated receptors provide promising templates to understand the molecular
      mechanism of receptor actions at the atomic level, and to deploy X-ray structures
      to be used for structure-based drug design. In the present work we also summarize
      recent findings about X-ray structures of ionotropic and metabotropic purinergic
      receptors and ectonucleotidases. A novel and prominent role as modulators of
      signal propagation in animal cells is played by microRNAs. By acting as genetic
      switches, they might become stringent regulators of the variety of cellular
      responses triggered by the dynamic interactions between purinergic receptors,
      nucleotides/nucleosides, transporters and ectonucleotidases. In this review we
      highlight data on the regulation of purinergic mechanisms by microRNAs. Finally,
      we would like to illustrate what information is still missing or needed for the
      acquisition of a more complete knowledge of purinergic signalling.

PMID- 22963440
TI  - P2X7 receptors: channels, pores and more.
AB  - Purine nucleotides are well established as extracellular signaling molecules.
      P2X7 receptors (P2X7Rs) are members of the family of ionotropic ATP-gated
      receptors. Their activity can be found in a limited number of cell types, but is
      readily detectable in cells of hemopoietic lineage including macrophages,
      microglia, and certain lymphocytes, and mediates the influx of Ca2+ and Na+ as
      well as the release of pro-inflammatory cytokines. Amongst P2X receptors, P2X7Rs
      behave as a bifunctional molecule. The binding of ATP induces within milliseconds
      the opening of a channel selective for small cations, and within seconds a larger
      pore opens which allows permeation by molecules with a mass of up to 900 Da. In
      humans at least, the P2RX7 gene is highly polymorphic, and genetic differences
      within P2X7R affect receptor pore formation and channel function. ATP can act as
      a neurotransmitter, while the presence of P2X7Rs on immune cells suggests that
      they also regulate immune function and inflammatory responses. In addition,
      activation of the P2X7R has dramatic cytotoxic properties. The role of
      extracellular ATP and purinoceptors in cytokine regulation and neurological
      disorders is, in fact, the focus of a rapidly expanding area of research. P2X7Rs
      may affect neuronal cell death by regulating the processing and release of
      interleukin-1beta, a key mediator in neurodegeneration, chronic inflammation, and
      chronic pain. Activation of P2X7Rs provides an inflammatory stimulus, and P2X7R
      deficient mice display a marked attenuation of inflammatory responses, including
      models of neuropathic and chronic inflammatory pain. Moreover, P2X7R activity, by
      regulating the release of pro-inflammatory cytokines, may be involved in the
      pathophysiology of neuropsychiatric disorders. The P2X7R may thus represent a
      critical communication link between the nervous and immune systems, while
      providing a target for therapeutic exploitation. In this review we discuss
      current biology and pharmacology of the P2X7R, as well as insights into the role
      for this receptor in neurological/psychiatric diseases.

PMID- 22963442
TI  - Ectonucleotidases and nucleotide/nucleoside transporters as pharmacological
      targets for neurological disorders.
AB  - Extracellular nucleotide and nucleoside are signaling molecules with a wide range
      of actions in the central nervous system (CNS). Extracellular ATP is released by
      several mechanisms involving ATP binding cassette transporters, hemichannels,
      P2X7 receptors, or volume-sensitive chloride channels. The levels of ATP and its
      hydrolysis product, adenosine, in the synaptic cleft are controlled by a complex
      cascade of cell surface-located enzymes collectively known as ectonucleotidases.
      There are four major families of ectonucleotidases: ecto-nucleoside triphosphate
      diphosphohydrolases (E-NTPDases), ecto-nucleotide
      pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases, and ecto-5'-
      nucleotidase. Besides the production of adenosine through nucleotide hydrolysis,
      this neuromodulator can be released as adenosine per se by equilibrative and/or
      concentrative nucleoside transporters. In this review, the involvement of
      nucleotide/nucleoside transporters and ectonucleotidases in the pathophysiology
      of brain disorders is discussed. The identification of compounds able to modulate
      the activity of these players in purinergic neurotransmission and their
      implications in neurological disorders as potential targets for drug discovery is
      also highlighted.

PMID- 22963444
TI  - Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n-3 fatty
      acids: molecular mechanisms and potential clinical applications.
AB  - The role of oxidative stress in ischaemic heart disease has been thoroughly
      investigated in humans. Increased levels of ROS (reactive oxygen species) and RNS
      (reactive nitrogen species) have been demonstrated during ischaemia and post
      ischaemic reperfusion in humans. Depending on their concentrations, these
      reactive species can act either as benevolent molecules that promote cell
      survival (at low-to-moderate concentrations) or can induce irreversible cellular
      damage and death (at high concentrations). Although high ROS levels can induce NF
      kappaB (nuclear factor kappaB) activation, inflammation, apoptosis or necrosis,
      low-to-moderate levels can enhance the antioxidant response, via Nrf2 (nuclear
      factor-erythroid 2-related factor 2) activation. However, a clear definition of
      these concentration thresholds remains to be established. Although a number of
      experimental studies have demonstrated that oxidative stress plays a major role
      in heart ischaemia/reperfusion pathophysiology, controlled clinical trials have
      failed to prove the efficacy of antioxidants in acute or long-term treatments of
      ischaemic heart disease. Oral doses of vitamin C are not sufficient to promote
      ROS scavenging and only down-regulate their production via NADPH oxidase, a
      biological effect shared by vitamin E to abrogate oxidative stress. However,
      infusion of vitamin C at doses high enough to achieve plasma levels of 10 mmol/l
      should prevent superoxide production and the pathophysiological cascade of
      deleterious heart effects. In turn, n-3 PUFA (polyunsaturated fatty acid)
      exposure leads to enhanced activity of antioxidant enzymes. In the present
      review, we present evidence to support the molecular basis for a novel
      pharmacological strategy using these antioxidant vitamins plus n-3 PUFAs for
      cardioprotection in clinical settings, such as post-operative atrial
      fibrillation, percutaneous coronary intervention following acute myocardial
      infarction and other events that are associated with ischaemia/reperfusion.

PMID- 22963445
TI  - Role of GLP-1 and DPP-4 in diabetic nephropathy and cardiovascular disease.
AB  - Although there have been major advances in the understanding of the molecular
      mechanisms that contribute to the development of diabetic nephropathy, current
      best practice still leaves a significant treatment gap. The incidence of diabetes
      and associated nephropathy is increasing, with the main cause of mortality being
      related to cardiovascular causes. Novel therapies which are both 'cardio-renal'
      protective seem the logical way forward. In the present review, we discuss the
      GLP-1 (glucagon-like peptide-1) receptor agonists and DPP-4 (dipeptidyl peptidase
      4) inhibitors (incretin-based therapies), which are novel antidiabetic agents
      used in clinical practice and their role in diabetic nephropathy with specific
      focus on renoprotection and surrogate markers of cardiovascular disease. We
      discuss the pleiotropic effects of the incretin-based therapies apart from
      glucose-lowering and highlight the non-GLP-1 effects of DPP (dipeptidyl
      peptidase) inhibition. Large-scale clinical studies with cardiovascular end
      points are underway; however, studies with renal end points are lacking but much
      needed.

PMID- 22963446
TI  - What's in a name: changing the terminology of autism diagnosis.

PMID- 22963447
TI  - IgG4-related orbital disease: a meta-analysis and review.
AB  - IgG4-related orbital disease (IgG4-ROD) is a recently described condition that
      may account for a significant proportion of idiopathic lymphoplasmacytic or
      sclerotic orbital lesions. This study is the first meta-analysis of published
      cases and reveals several differences between IgG4-related disease affecting the
      orbit and that affecting the pancreas. IgG4-ROD affects a slightly younger group
      of patients, affects men and women approximately equally, is commonly associated
      with salivary gland lesions, is associated with a relatively higher serum IgG4
      and may confer an increased risk of non-Hodgkin Lymphoma. Its pathogenesis may
      involve an immune response to antigen exposure in the upper aerodigestive tract.

PMID- 22963441
TI  - P2Y receptors in the mammalian nervous system: pharmacology, ligands and
      therapeutic potential.
AB  - P2Y receptors for extracellular nucleotides are coupled to activation of a
      variety of G proteins and stimulate diverse intracellular signaling pathways that
      regulate functions of cell types that comprise the central nervous system (CNS).
      There are 8 different subtypes of P2Y receptor expressed in cells of the CNS that
      are activated by a select group of nucleotide agonists. Here, the agonist
      selectivity of these 8 P2Y receptor subtypes is reviewed with an emphasis on
      synthetic agonists with high potency and resistance to degradation by
      extracellular nucleotidases that have potential applications as therapeutic
      agents. In addition, the recent identification of a wide variety of subtype
      selective antagonists is discussed, since these compounds are critical for
      discerning cellular responses mediated by activation of individual P2Y receptor
      subtypes. The functional expression of P2Y receptor subtypes in cells that
      comprise the CNS is also reviewed and the role of each subtype in the regulation
      of physiological and pathophysiological responses is considered. Other topics
      include the role of P2Y receptors in the regulation of blood-brain barrier
      integrity and potential interactions between different P2Y receptor subtypes that
      likely impact tissue responses to extracellular nucleotides in the CNS. Overall,
      current research suggests that P2Y receptors in the CNS regulate repair
      mechanisms that are triggered by tissue damage, inflammation and disease and thus
      P2Y receptors represent promising targets for the treatment of neurodegenerative
      diseases.

PMID- 22963448
TI  - How children use drawing to regulate their emotions.
AB  - We examined two ways in which drawing may function to elevate mood in children
      venting (expressing negative feelings) and distraction (expressing something
      unrelated to the negative feelings). We examined the effectiveness of drawing as
      an emotion regulator when drawing is used to vent versus distract (Study 1) and
      tested whether the effects found are specific to the activity of creating one's
      own drawing or generalisable to a drawing activity in which children had to copy
      another's drawing (Study 2). To induce a negative mood, we asked children to
      think of a disappointing event. Mood was assessed before and after the assigned
      activity. In both studies, mood improved significantly more in the distract than
      in the vent or copy condition. Study 1 demonstrates that drawing improves mood in
      children via distraction and not via venting. Study 2 demonstrates that this
      effect is specific to a drawing task in which an image is freely constructed.
      When a copying task is used, the effect disappears.

PMID- 22963450
TI  - Does two-dimensional image reconstruction from three-dimensional full volume
      echocardiography improve the assessment of left ventricular morphology and
      function?
AB  - AIMS: (i) To investigate geometric differences between apical views of the left
      ventricle (LV) derived from standard 2D echocardiography (std2D) and triplane
      (TP) views, as well as the "ideally" reconstructed 2D (rec2D) views derived from
      3D full volume (3DFV) acquisitions, and their influence on the assessment of LV
      morphology and function. (ii) To determine the feasibility and accuracy of the
      automatic reconstruction of 2D apical views from 3DFV datasets. METHODS AND
      RESULTS: In 59 patients with structurally normal, dilated, and hypertrophic
      hearts, rec2D was reconstructed manually and automatically and compared to std2D,
      TP, and 3DFV regarding the image plane orientation (true vs. ideal probe
      position, plane intersection angles), LV dimensions, volumes, and EF. The ideal
      probe position deviated from the true one by 6.9 +/- 4.1 mm and 9.5 +/- 4.5 mm,
      for manually and automatically rec2D, respectively, regardless of LV geometry.
      The mean difference +/- SD between manual and automatic reconstruction was -2.5
      +/- 4.4 mm. LV long axis was measured minimally, but significantly longer in
      rec2D than std2D and TP. LV volumes and EF did not differ between methods. The
      intersection angle of the two-chamber view and the three-chamber view with the
      four-chamber view for manual and automatic reconstruction was 53 degrees  +/- 7
      degrees  and 129 degrees  +/- 7 degrees  and 60 degrees  and 130 degrees ,
      respectively. CONCLUSION: Ideal reconstruction of nonforeshortened 2D images from
      3DFV does not lead to a relevant improvement in image geometry or the assessment
      of LV morphology and function. The automatic reconstruction algorithm deviates
      only slightly from manual results.

PMID- 22963449
TI  - Analysis of and prognostic information from disseminated tumour cells in bone
      marrow in primary breast cancer: a prospective observational study.
AB  - BACKGROUND: Disseminated tumour cells (DTCs) in the bone marrow of patients with
      breast cancer have been identified as an independent predictor of poor prognosis
      in patients with non-metastatic disease. This prospective study aimed to evaluate
      the presence and prognostic value of DTCs in the bone marrow of female patients
      with primary breast cancer. METHODS: Between 1999 and 2003, bone marrow aspirates
      were obtained from patients at the time of surgery for primary invasive breast
      cancer. DTCs in bone marrow were identified using monoclonal antibodies against
      cytokeratins for detection of epithelial cells. The detection of DTCs was related
      to clinical follow-up with distant disease-free survival (DDFS) and breast cancer
      specific survival as endpoints. Bone marrow aspirates from adult healthy bone
      marrow donors were analysed separately. RESULTS: DTCs were analysed in 401
      patients, and cytokeratin-positive cells were found in 152 of these (38%). An
      immunofluorescence (IF) staining procedure was used in 327 patients, and
      immunocytochemistry (IC) was performed in 74 patients. The IF-based method
      resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p =
      0.11). The presence of DTCs in bone marrow was not significantly related to
      patient or tumour characteristics. The presence of DTCs was not a prognostic
      factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63
      2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic
      factors were lymph node metastases, oestrogen receptor positivity, Nottingham
      histological grade, and tumour size using Cox univariate analysis. The analyses
      were positive for epithelial cells in bone marrow from adult healthy donors in 19
      (25%) samples. CONCLUSIONS: The detection of DTCs in bone marrow in primary
      breast cancer was previously shown to be a predictor of poor prognosis. We were
      not able to confirm these results in a prospective cohort including unselected
      patients before the standard procedure was established. Future studies with a
      standardised patient protocol and improved technique for isolating and detecting
      DTCs may reveal the clinical applications of DTC detection in patients with
      micrometastases in the bone marrow.

PMID- 22963451
TI  - Multiannual observations of acetone, methanol, and acetaldehyde in remote
      tropical atlantic air: implications for atmospheric OVOC budgets and oxidative
      capacity.
AB  - Oxygenated volatile organic compounds (OVOCs) in the atmosphere are precursors to
      peroxy acetyl nitrate (PAN), affect the tropospheric ozone budget, and in the
      remote marine environment represent a significant sink of the hydroxyl radical
      (OH). The sparse observational database for these compounds, particularly in the
      tropics, contributes to a high uncertainty in their emissions and atmospheric
      significance. Here, we show measurements of acetone, methanol, and acetaldehyde
      in the tropical remote marine boundary layer made between October 2006 and
      September 2011 at the Cape Verde Atmospheric Observatory (CVAO) (16.85 degrees 
      N, 24.87 degrees  W). Mean mixing ratios of acetone, methanol, and acetaldehyde
      were 546 +/- 295 pptv, 742 +/- 419 pptv, and 428 +/- 190 pptv, respectively,
      averaged from approximately hourly values over this five-year period. The CAM
      Chem global chemical transport model reproduced annual average acetone
      concentrations well (21% overestimation) but underestimated levels by a factor of
      2 in autumn and overestimated concentrations in winter. Annual average
      concentrations of acetaldehyde were underestimated by a factor of 10, rising to a
      factor of 40 in summer, and methanol was underestimated on average by a factor of
      2, peaking to over a factor of 4 in spring. The model predicted summer minima in
      acetaldehyde and acetone, which were not apparent in the observations. CAM-Chem
      was adapted to include a two-way sea-air flux parametrization based on seawater
      measurements made in the Atlantic Ocean, and the resultant fluxes suggest that
      the tropical Atlantic region is a net sink for acetone but a net source for
      methanol and acetaldehyde. Inclusion of the ocean fluxes resulted in good model
      simulations of monthly averaged methanol levels although still with a 3-fold
      underestimation in acetaldehyde. Wintertime acetone levels were better simulated,
      but the observed autumn levels were more severely underestimated than in the
      standard model. We suggest that the latter may be caused by underestimated
      terrestrial biogenic African primary and/or secondary OVOC sources by the model.
      The model underestimation of acetaldehyde concentrations all year round implies a
      consistent significant missing source, potentially from secondary chemistry of
      higher alkanes produced biogenically from plants or from the ocean. We estimate
      that low model bias in OVOC abundances in the remote tropical marine atmosphere
      may result in up to 8% underestimation of the global methane lifetime due to
      missing model OH reactivity. Underestimation of acetaldehyde concentrations is
      responsible for the bulk (~70%) of this missing reactivity.

PMID- 22963453
TI  - Obesity and outcomes in patients hospitalized with pneumonia.
AB  - Studies suggest obesity is paradoxically associated with better outcomes for
      patients with pneumonia. Therefore, we examined the impact of obesity on short
      term mortality in patients hospitalized with pneumonia. For 2 years clinical and
      radiographic data were prospectively collected on all consecutive adults admitted
      with pneumonia to six hospitals in Edmonton, Alberta, Canada. We identified 907
      patients who also had body mass index (BMI, kg/m(2)) collected and categorized
      them as underweight (BMI < 18.5), normal (18.5 to <25), overweight (25 to <30)
      and obese (>30). Overall, 65% were >65 years, 52% were female, and 15% reported
      recent weight loss. Eighty-four (9%) were underweight, 358 (39%) normal, 228
      (25%) overweight, and 237 (26%) obese. Two-thirds had severe pneumonia (63% PSI
      Class IV/V) and 79 (9%) patients died. In-hospital mortality was greatest among
      those that were underweight (12 [14%]) compared with normal (36 [10%]),
      overweight (21 [9%]) or obese (10 [4%], p <0.001 for trend). Compared with those
      of normal weight, obese patients had significantly lower rates of in-hospital
      mortality in multivariable logistic regression analyses: adjusted odds ratio
      (OR), 0.46; 95% CI, 0.22-0.97; p 0.04. However, compared with patients with
      normal weight, neither underweight (adjusted OR, 1.13; 95% CI, 0.54-2.4; p 0.7)
      nor overweight (adjusted OR, 0.94; 95% CI, 0.52-1.69; p 0.8) were associated with
      in-hospital mortality. In conclusion, in patients hospitalized with pneumonia,
      obesity was independently associated with lower short-term mortality, while
      neither being underweight nor overweight were. This suggests a protective
      influence of BMIs > 30 kg/m(2) that requires better mechanistic understanding.

PMID- 22963454
TI  - Human exposure to lead, cadmium and mercury through fish and seafood product
      consumption in Italy: a pilot evaluation.
AB  - The presence of selected toxic heavy metals, such as cadmium (Cd), lead (Pb) and
      mercury (Hg), was investigated in fish and seafood products, namely, blue mussel,
      carpet shell clam, European squid, veined squid, deep-water rose shrimp, red
      mullet, European seabass, gilthead seabream, Atlantic cod, European hake,
      Atlantic bluefin tuna and swordfish so as to assess their human exposure through
      diet. Metals were detected by quadrupole inductively coupled plasma mass
      spectrometry (Q-ICP-MS) and hydride generation atomic absorption spectrometry (Hg
      AAS). Measurements of Cd, Pb and Hg were performed by means of analytical methods
      validated in compliance with UNI CEI EN ISO/IEC 17025 [2005. General requirements
      for the competence of testing and calibration laboratories. Milano (Italy): UNI
      Ente Nazionale Italiano di Unificazione]. The exposure assessment was undertaken
      matching the levels of Cd, Pb and total Hg with consumption data related to fish
      and seafood products selected for this purpose. In order to establish human
      health implications, the estimated weekly intakes (EWIs) for Cd, Pb and Hg were
      compared with the standard tolerable weekly intakes (TWI) for Cd and provisional
      tolerable weekly intakes (PTWIs) for Pb and Hg stipulated by the European Food
      Safety Authority (EFSA) and the Food and Agriculture Organization/World Health
      Organization (FAO/WHO) Joint Expert Committee on Food Additives (JECFA). The
      found metal concentrations were largely below the maximum levels (MLs)
      established at the European Union level with the exception of Cd. This metal
      exceeded the MLs in squid, red mullet, European hake and Atlantic cod. Squid and
      blue mussel showed the highest Pb concentrations which accounted for 60% and 10%
      of the MLs, respectively. Highest Hg levels were found in predatory fish. The
      concentrations of Hg in swordfish, Atlantic bluefin tuna and red mullet accounted
      for 50%, 30% and 30% of the MLs, respectively. The EWIs for Cd, Pb and Hg related
      to the consumption of fish and seafood products by the median of the Italian
      total population accounted for 20%, 1.5% and 10% of the standard TWI for Cd as
      well as PTWIs for Pb and Hg, respectively. Furthermore, the EWIs estimated using
      consumption data concerning Italian consumers did not exceed the standard TWI and
      PTWIs, except for Cd at 95th percentile.

PMID- 22963455
TI  - Redox properties of Abarema cochliacarpos (Gomes) Barneby & Grime (Fabaceae) stem
      bark ethanol extract and fractions.
AB  - The redox properties of the hydroethanol extract (EE) and its ethyl acetate (EAF)
      and hydromethanol (HMF) fractions obtained from Abarema cochliacarpos (Gomes)
      Barneby & Grimes stem bark were evaluated. EAF had the highest total phenol
      content (848.62 +/- 78.18 mg g-1), while EE showed the highest content of
      catechin (71.2 ug g-1). EE, EAF and HMF exhibited the highest levels of
      antioxidant activity at 100 and 1000 ug mL-1 when the non-enzymatic antioxidant
      potential was evaluated by the total reactive antioxidant potential, total
      antioxidant reactivity and nitric oxide scavenging assays. In addition, EAF and
      HMF showed SOD-like activity. The results for EE, EAF and HMF in this study
      showed that A. cochliacarpos (Gomes) Barneby & Grimes stem bark have redox
      properties and may be able to help the endogenous enzymatic and non-enzymatic
      systems to keep the redox balance.

PMID- 22963456
TI  - Regulation of neuraminidase expression in Streptococcus pneumoniae.
AB  - BACKGROUND: Sialic acid (N-acetylneuraminic acid; NeuNAc) is one of the most
      important carbohydrates for Streptococcus pneumoniae due of its role as a carbon
      and energy source, receptor for adhesion and invasion and molecular signal for
      promotion of biofilm formation, nasopharyngeal carriage and invasion of the lung.
      RESULTS: In this work, NeuNAc and its metabolic derivative N-acetyl mannosamine
      (ManNAc) were used to analyze regulatory mechanisms of the neuraminidase locus
      expression. Genomic and metabolic comparison to Streptococcus mitis,
      Streptococcus oralis, Streptococcus gordonii and Streptococcus sanguinis
      elucidates the metabolic association of the two amino sugars to different parts
      of the locus coding for the two main pneumococcal neuraminidases and confirms the
      substrate specificity of the respective ABC transporters. Quantitative gene
      expression analysis shows repression of the locus by glucose and induction of all
      predicted transcriptional units by ManNAc and NeuNAc, each inducing with higher
      efficiency the operon encoding for the transporter with higher specificity for
      the respective amino sugar. Cytofluorimetric analysis demonstrated enhanced
      surface exposure of NanA on pneumococci grown in NeuNAc and ManNAc and an
      activity assay allowed to quantify approximately twelve times as much
      neuraminidase activity on induced cells as opposed to glucose grown cells.
      CONCLUSIONS: The present data increase the understanding of metabolic regulation
      of the nanAB locus and indicate that experiments aimed at the elucidation of the
      relevance of neuraminidases in pneumococcal virulence should possibly not be
      carried out on bacteria grown in glucose containing media.

PMID- 22963457
TI  - Acetalization allows the photoheterolysis of the Ar-Cl bond in
      chlorobenzaldehydes and chloroacetophenones.
AB  - The nonaccessibility of phenyl cations by irradiation of electron-poor aryl
      chlorides was circumvented by transforming the carbonyl group of aromatic ketones
      or aldehydes into the corresponding 1,3-dioxolanes and the carboxyl group of
      benzoate ester into an orthoester functionality. This transformation allowed the
      heterolytic photoactivation of the Ar-Cl bond in protic media and the generation
      of phenyl cations. In the presence of pi-bond nucleophiles, arylated products
      were obtained in good to excellent yields.

PMID- 22963458
TI  - Modeling of the structure of sodium borosilicate glasses using pair potentials.
AB  - Structural models of sodium borosilicate glasses were prepared by means of
      molecular dynamics (MD) technique using pair potentials over a wide compositional
      range. The local structures around B, O, and Si obtained from the structural
      models were compared with experimental (11)B NMR, (17)O NMR, and (29)Si NMR data.
      It was found that atomic arrangements of B, O, and Si in the structural models
      were similar to the experimental results indicating that the simulations can
      reproduce the chemical bonds of the real glasses. These results confirm that even
      if the MD technique using the pair potentials is quite simple, it is enough to
      capture the essence of the amorphous materials. In the linkage of the cation
      oxygen polyhedra, the differences were observed between the structural models and
      the experimental results. The factors responsible for these differences are
      discussed with respect to the equilibrium reactions between the cation-oxygen
      polyhedra at a higher temperature. The discussion suggests that the differences
      were caused by the extremely higher quenching rate than the real glasses as well
      as by the simplicity of our pair potential and the smaller size of the unit cell.

PMID- 22963459
TI  - Relationship between serum adiponectin levels and age in healthy subjects and
      patients with type 2 diabetes.
AB  - OBJECTIVE: Serum adiponectin levels are affected by gender, body fat mass,
      several pathological factors or therapeutic interventions and it might be also
      affected by age. This study aimed to investigate the relationship between serum
      adiponectin levels and age in several physiological states. DESIGN, PATIENTS AND
      MEASUREMENTS: The study was carried out in 21 100 healthy subjects (12 363 men
      and 8737 women) and 1833 patients with type 2 diabetes (1233 men and 600 women).
      Physical and demographic characteristics were recorded, and blood samples were
      collected to measure serum adiponectin levels. Using these data, we determined
      the relationships between serum adiponectin levels and various parameters,
      including age. RESULTS: Serum adiponectin levels increased with increasing age of
      healthy subjects and in patients with diabetes, in both men and women. Serum
      adiponectin levels were positively correlated with age in healthy subjects and
      patients with diabetes, in both men and women. In stepwise multiple regression
      analysis with serum adiponectin levels as the dependent variable and
      physiological characteristics as explanatory variables, age was significantly and
      independently associated with serum adiponectin levels in each of these groups of
      subjects. CONCLUSIONS: Serum adiponectin levels are significantly and positively
      associated with age in healthy subjects and in patients with diabetes. This
      association is independent of renal function, body fat status, glucose metabolism
      and lipid profiles.

PMID- 22963461
TI  - Growth of exclusively breastfed and self-weaned children of Greece aged 0-36
      months.
AB  - OBJECTIVE: Breastfeeding is recognized as an important public health issue with
      substantial social and economic implications. Moreover, the growth of exclusively
      breastfed babies differs from that of their formula-fed counterparts. The purpose
      of this study was to evaluate the physical growth of exclusively breastfed and
      self-weaned boys and girls of Greece 0-36 months of age. SUBJECTS AND METHODS:
      The physical growth of children was monitored from birth up to 36 months of age.
      Body weight, length/height, and head circumference were recorded. The study
      population included 101 boys and 105 girls who were recruited consecutively from
      a private breastfeeding clinic in the second largest city of Greece and through
      La Leche League groups throughout the country during 2000 to 2005. All infants
      were exclusively breastfed for >= 6 months. Anthro software (
      www.who.int/childgrowth/software/en/index.html ) was used to compare the data of
      our study population and the World Health Organization standards for weight,
      length/height, and head circumference for age. RESULTS: Male and female infants
      at 12 months had almost tripled their weight (192% and 190% increase,
      respectively) and had increased their length (height) by 48% and 47%,
      respectively, and head circumference had increased by 35% and 33%, respectively.
      In both sexes the relative length/height and the head circumference-for-age
      increase rates were higher from the first to the second month of life than at any
      other period. CONCLUSIONS: Long-term exclusively breastfed infants grow normally.
      Hence, no recommendations for the interruption of lactation and/or
      supplementation with formula are justified.

PMID- 22963460
TI  - Effect of high-dose intravenous vitamin C on inflammation in cancer patients.
AB  - BACKGROUND: An inflammatory component is present in the microenvironment of most
      neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are
      associated with poor prognosis and decreased survival in many types of
      cancer.Vitamin C has been suggested as having both a preventative and therapeutic
      role in a number of pathologies when administered at much higher-than-recommended
      dietary allowance levels.Since in vitro studies demonstrated inhibition of pro
      inflammatory pathways by millimolar concentrations of vitamin C, we decided to
      analyze the effects of high dose IVC therapy in suppression of inflammation in
      cancer patients. METHODS: 45 patients with prostate cancer, breast cancer,
      bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B
      cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5
      g -50 g) after standard treatments by conventional methods.CRP and tumor markers
      were measured in serum or heparin-plasma as a routine analysis. In addition,
      serum samples were collected before and after the IVCs for the cytokine kit
      tests. RESULTS: According to our data positive response to treatment, which was
      demonstrated by measurements of C- reactive protein, was found in 75% of patients
      and progression of the inflammation in 25% of patients. IVC treatments on all
      aggressive stage cancer patients showed the poor response of treatment.There was
      correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in
      the levels of C-reactive protein.Our test of the effect of IVC on pro
      inflammatory cytokines demonstrated that inflammation cytokines IL-1alpha, IL-2,
      IL-8, TNF-alpha, chemokine eotaxin and CRP were reduced significantly after
      treatments. CONCLUSIONS: The high dose intravenous ascorbic acid therapy affects
      C-reactive protein levels and pro-inflammation cytokines in cancer patients. In
      our study, we found that modulation of inflammation by IVC correlated with
      decreases in tumor marker levels.In summary, our data support the hypothesis that
      high dose intravenous ascorbate treatments may reduce inflammation in cancer
      patients. Our results suggest that further investigations into the use of IVC to
      reduce inflammation in diseases where inflammation is relevant are warranted.

PMID- 22963462
TI  - Duration of breastfeeding and distoclusion in the deciduous dentition.
AB  - OBJECTIVE: This study investigated the association between duration of
      breastfeeding and occurrence of distoclusion in preschoolers with complete
      deciduous dentition. SUBJECTS AND METHODS: A cross-sectional study nested within
      a cohort of 153 Brazilian children was conducted. The outcome of interest was
      presence of distoclusion as diagnosed at dental assessment between 3 and 5 years
      of age. Data on the main exploratory variable (duration of breastfeeding) and
      other variables that might influence the study outcome (use of dummy/pacifier,
      bottle feeding, and thumb sucking) were collected by a blinded examiner at 7, 30,
      60, 120, and 180 days of life and at dental assessment. Poisson regression was
      used to test for the association between exposure and the outcome of interest.
      RESULTS: The prevalence of distoclusion was 47.7%. Multivariate analysis showed
      that breastfeeding afforded some protection against distoclusion, after adjusting
      for confounding factors such as pacifier use and bottle feeding. In children
      breastfed for 12 months or more, the prevalence of distoclusion at 3-5 years of
      age was 56% lower than in those breastfed for shorter periods (prevalence
      ratio=0.44; 95% confidence interval 0.23-0.82). CONCLUSION: Breastfeeding for 12
      months or longer significantly reduces the prevalence of distoclusion in the
      deciduous dentition.

PMID- 22963463
TI  - Sterile stockinette in orthopaedic surgery: a possible pathway for infection.
AB  - BACKGROUND: The prevention of infection in joint replacement surgery is
      important. Preparing and draping the patient is fundamental to maintaining
      sterility of the operative field. One method of draping for total knee
      replacement (TKR) surgery involves cleaning the operative leg with antiseptic
      wash then covering the un-prepped foot with a sterile stockinette to sequester
      the foot from the sterile field. There are two main methods for applying this
      stockinette. This randomized, blinded control trial simulates stockinette
      application to assess if it prevents proximal microbial migration into the
      sterile field. METHOD: To simulate microbial presence, ultraviolet fluorescent
      powder Glitterbug PowderTM (Arrow Scientific Pty Ltd, Lane Cove, NSW, Australia)
      was applied to volunteers' feet to the level where antiseptic wash would
      routinely stop during preparation. The stockinette was applied. Two methods of
      application (above and below knee) and two surgeons were used. These were
      randomized for each application. The drapes were removed and a blinded assistant
      measured the distance of proximal spread of Glitterbug PowderTM. RESULTS: Both
      methods of application were associated with considerable proximal spread of
      Glitterbug PowderTM. For the below knee method, mean proximal spread distance of
      49.19%; for the above knee, mean of 71.8% proximal spread (P = 0.038).
      Multivariate linear regression analysis demonstrated that method and location of
      the contamination were predictive of the area of contamination and the percentage
      of the leg contaminated. No other factors (surgeon, gender, hirsute score) were
      predictive of either area or percentage contamination. CONCLUSION: The surgical
      field for TKRs may be contaminated by significant proximal microbial spread from
      the unprepared foot with the use of a sterile stockinette drape.

PMID- 22963465
TI  - Growth factor binding on heparin mimetic peptide nanofibers.
AB  - Immobilization of growth factors in scaffolds is important for controlling their
      dose and bioactivity for regenerative medicine applications. Although numerous
      covalent and noncovalent immobilization strategies have been proposed, better
      growth factor loading and dose control inside the scaffold is necessary. Nature
      of the binding site on the growth factor interacting with scaffold is critical
      for preserving and achieving maximal growth factor functionality, which has been
      a relatively less emphasized issue in previous studies. We recently reported
      heparin mimetic peptide nanofibers, which mimic chemistry of heparan sulfates.
      Heparin mimetic nanofibers were shown to bind to vascular endothelial growth
      factor (VEGF) and direct endothelial cells to angiogenesis. Here, we further
      investigated interactions between heparin mimetic peptide nanofibers and growth
      factors. We tested bioactivity of the nanofiber bound growth factors in order to
      understand the potential use of these peptide nanofiber scaffolds as analogues of
      heparan sulfates. We observed that heparin mimetic peptide nanofibers demonstrate
      better binding profiles to VEGF, hepatocyte growth factor (HGF), and fibroblast
      growth factor-2 (FGF-2) than control peptide nanofibers. We also identified that
      the heparin-binding domain of VEGF is critical for its interaction with these
      nanofibers. However, the heparin-binding site is not indispensable for binding of
      all growth factors to nanofibers. We also showed that binding of growth factors
      to nanofibers does not cause any loss in bioactivity through in vitro cell
      culture assays with PC-12 cells. These results reveal that heparin mimetic
      peptide nanofibers can effectively mimic heparan sulfates in extracellular matrix
      and provide an optimal milieu for spatial presentation of important growth
      factors. These properties make peptide nanofiber scaffolds promising materials
      for regenerative medicine applications through efficient and precisely controlled
      growth factor delivery.

PMID- 22963464
TI  - Variation in exposure to Anopheles gambiae salivary gland peptide (gSG6-P1)
      across different malaria transmission settings in the western Kenya highlands.
AB  - BACKGROUND: The existing metrics of malaria transmission are limited in
      sensitivity under low transmission intensity. Robust surveillance systems are
      needed as interventions to monitor reduced transmission and prevention of rapid
      reintroduction. Serological tools based on antibody responses to parasite and
      vector antigens are potential tools for transmission measurements. The current
      study sought to evaluate antibody responses to Anopheles gambiae salivary gland
      peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in
      different transmission settings and seasons. The comparison between anti-MSP
      1(19) IgG immune responders and non-responders allowed exploring the robustness
      of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria
      transmission. METHODS: Total IgG levels to gSG6-P1 were measured in an age
      stratified cohort (< 5, 5-14 and >= 15 years) in a total of 1,366 participants
      from three localities in western Kenya [Kisii (hypoendemic), Kakamega
      (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were
      additionally tested for MSP-1(19) specific responses during a low and a high
      malaria transmission seasons. Antibody prevalence and levels were compared
      between localities with different transmission intensities. Regression analysis
      was performed to examine the association between gSG6-P1 and MSP-1(19)
      seroprevalence and parasite prevalence. RESULT: Seroprevalence of gSG6-P1 in the
      uphill population was 36% while it was 50% valley bottom (chi(2) = 13.2, df = 1,
      p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as
      high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and
      showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-1(19)
      antibodies were almost three times higher than the odds of seronegatives (OR =
      2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii,
      Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the equivalent gSG6-P1
      seroprevalence were 28%, 34% and 54%, respectively. CONCLUSION: The
      seroprevalence of IgG to gSG6-P1 was sensitive and robust in distinguishing
      between hypo, meso and hyper transmission settings and seasonal fluctuations.

PMID- 22963466
TI  - Spectroelectrochemical investigation of an electrogenerated graphitic oxide solid
      electrolyte interphase.
AB  - This study investigates electrogenerated graphitic oxides (EGO) on the surface of
      carbon optically transparent electrodes (C-OTEs) using a combined UV-vis
      spectroelectrochemical approach. By monitoring the pi-pi* aromatic carbon
      transition for reduced GO (270 nm) and GO (230 nm), we observe the growth of GO
      in KCl upon applying oxidizing potentials. X-ray photoelectron spectroscopy (XPS)
      and time-of-flight secondary ion mass spectroscopy (TOF-SIMS) are used to confirm
      sample composition and location of salt ions within the electrode. Formation of
      EGO stable enough to be observed by UV-vis is found to be unique to alkali
      chloride supporting electrolytes due to formation of a solid-electrolyte
      interphase (SEI) which incorporates the alkali cation to stabilize the negatively
      charged oxygen functional groups while the presence of chloride anion acts as a
      passivation agent that protects the electrode surface from dissolution. The
      spectroelectrochemical approach highlights the detection and study of EGO that
      cannot be detected by electrochemical measurements. Specifically, the amount of
      EGO observed by UV-vis scales with increasing cation size (Li(+), Na(+), K(+))
      despite all the cations showing identical electrochemical response.

PMID- 22963467
TI  - Trigeminal neuralgia as the sole symptom of pancreatic cancer.
AB  - Trigeminal neuralgia (TN) is a condition characterized by brief electric shock
      like pains in the topography of the trigeminal nerve. The most common cause of
      this disorder is the compression of the trigeminal nerve root by tortuous or
      aberrant vessels. In this report, we describe a patient who presented due to
      paroxysmal and excruciating facial pain that was found to be secondary to
      pancreatic cancer.

PMID- 22963468
TI  - Temperature-dependent development and survival of Brazilian populations of the
      Mediterranean fruit fly, Ceratitis capitata, from tropical, subtropical and
      temperate regions.
AB  - The Mediterranean fruit fly Ceratitis capitata (Wiedemann) (Diptera: Tephritidae)
      is one of the principal exotic pests affecting Brazilian production in the
      northeastern and southeastern regions of Brazil. In the south, it is has
      potential as a serious threat to temperate-climate fruit farms, since it is
      already found in urban and suburban communities in this region. We studied the
      biological characteristics of C. capitata populations from Pelotas-RS (temperate
      climate), Petrolina-PE (tropical), and Campinas-SP (subtropical). Ceratitis
      capitata biology was studied under controlled temperature (15, 20, 25, 30, and 35
      +/- 1  degrees C), 70 +/- 10% RH, and 14:10 L:D photoperiod. The duration and
      survival rate of the egg, larval, and pupal stages were evaluated and the thermal
      requirements of these three populations were determined. The duration and
      survival of these developmental stages varied with temperature, with similar
      values for the three populations, except for some variation in the egg phase. Egg
      to adult developmental time for all three populations was inversely proportional
      to temperature; from 15 to 30  degrees C developmental time varied from 71.2 to
      17.1, 70.2 to 17.1, and 68.5 to 16.9 days, respectively. Survival during
      development was affected at 15 to 30  degrees C, and differed significantly from
      survival at 20 to 25  degrees C. At 35  degrees C, immature stages did not
      develop. The basal temperature and degree-day requirement were similar for all
      immature stages except for the egg stage. The basal temperatures and thermal
      constants were 9.30 and 350, 8.47 and 341, and 9.60  degrees C and 328 degree
      days for the Pelotas, Petrolina, and Campinas populations, respectively. Results
      suggested that survival and thermal requirements are similar for these tropical,
      subtropical, and temperate populations of C. capitata, and demonstrate the
      species' capacity to adapt to different climate conditions.

PMID- 22963469
TI  - Variant explosion.

PMID- 22963472
TI  - Profile of Janet Rossant. Interview by Kristie Nybo.

PMID- 22963474
TI  - Unraveling autism one de novo mutation at a time.

PMID- 22963475
TI  - qRT-PCR with saliva samples.

PMID- 22963476
TI  - A system for the measurement of gene targeting efficiency in human cell lines
      using an antibiotic resistance-GFP fusion gene.
AB  - Gene targeting in a broad range of human somatic cell lines has been hampered by
      inefficient homologous recombination. To improve this technology and facilitate
      its widespread application, it is critical to first have a robust and efficient
      research system for measuring gene targeting efficiency. Here, using a fusion
      gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP
      (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the
      ratio of homologous to random integration (H/R ratio) of targeting vectors into
      the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP
      were efficiently established from two human somatic cell lines. Established HygR
      5' EGFP reporter clones retained their capacity to monitor gene targeting
      efficiency for a longer duration than a conventional reporter system using an
      unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced
      previous findings of gene targeting frequency being up-regulated by the use of an
      adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer
      homology arm in a targeting vector, suggesting that this system accurately
      monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the
      development of an efficient AAV-based gene targeting technology.

PMID- 22963478
TI  - Streamlined extract preparation for Escherichia coli-based cell-free protein
      synthesis by sonication or bead vortex mixing.
AB  - Escherichia coli-based cell extract is a vital component of inexpensive and high
      yielding cell-free protein synthesis reactions. However, effective preparation of
      E. coli cell extract is limited to high-pressure (French press-style or impinge
      style) or bead mill homogenizers, which all require a significant capital
      investment. Here we report the viability of E. coli cell extract prepared using
      equipment that is both common to biotechnology laboratories and able to process
      small volume samples. Specifically, we assessed the low-capital-cost lysis
      techniques of: (i) sonication, (ii) bead vortex mixing, (iii) freeze-thaw
      cycling, and (iv) lysozyme incubation to prepare E. coli cell extract for cell
      free protein synthesis (CFPS). We also used simple shake flask fermentations with
      a commercially available E. coli strain. In addition, RNA polymerase was
      overexpressed in the E. coli cells prior to lysis, thus eliminating the need to
      add independently purified RNA polymerase to the CFPS reaction. As a result, high
      yielding E. coli-based extract was prepared using equipment requiring a reduced
      capital investment and common to biotechnology laboratories. To our knowledge,
      this is the first successful prokaryote-based CFPS reaction to be carried out
      with extract prepared by sonication or bead vortex mixing.

PMID- 22963477
TI  - Cell-free synthesis of functional and endotoxin-free antibody Fab fragments by
      translocation into microsomes.
AB  - A eukaryotic cell-free system based on Spodoptera frugiperda cells was developed
      for the convenient synthesis of Fab antibody fragments and other disulfide bridge
      containing proteins. The system uses (i) a cell lysate that is mildly prepared
      under slightly reduced conditions, thus maintaining the activity of vesicles
      derived from the endoplasmic reticulum, (ii) signal peptide dependent
      translocation into these vesicles, and (iii) a redox potential based on reduced
      and oxidized glutathione. Monomeric heavy and light immunoglobulin chains are
      almost completely converted to highly active dimeric Fab joined by intermolecular
      disulfide bridges without supplementation of chaperones or protein disulfide
      isomerase. The applicability of the system is demonstrated by the synthesis of
      anti-lysozyme and anti-CD4 Fab antibody fragments yielding approximately 10 ug
      Fab per milliliter reaction mixture. The lack of endotoxins in this system is a
      prerequisite that synthesized Fab can be applied directly using whole synthesis
      reactions in cell-based assays that are sensitive to this substance class.
      Moreover, the system is compatible with PCR-generated linear templates enabling
      automated generation of antibody fragments in a high-throughput manner, and
      facilitating its application for screening and validation purposes.

PMID- 22963479
TI  - ISH-guided freeze-matrix assisted punches: technique for extracting punches from
      thin slide-mounted tissues for DNA methylation analysis.
AB  - Dissection of discrete brain regions for molecular analysis is complicated by
      trade-offs between accuracy, flexibility, and costs. We developed a flexible and
      cost-effective method, in situ hybridization (ISH) guided freeze-matrix assisted
      punches (IFAP), for extracting nanogram quantities of DNA from slide-mounted
      sections as thin as 12 MUm. Using ISH to localize regions of interest, tissue is
      targeted by applying a small bead of M-1 embedding matrix onto cryosections, snap
      freezing, and collecting the beads for nucleic acid purification. The method
      quantitatively recovers RNA and DNA usable for PCR and DNA methylation analysis.

PMID- 22963480
TI  - Improving the limit of detection for Sanger sequencing: a comparison of
      methodologies for KRAS variant detection.
AB  - Fluorescent dye terminator Sanger sequencing (FTSS), with detection by automated
      capillary electrophoresis (CE), has long been regarded as the gold standard for
      variant detection. However, software analysis and base-calling algorithms used to
      detect mutations were largely optimized for resequencing applications in which
      different alleles were expected as heterozygous mixtures of 50%. Increasingly,
      the requirements for variant detection are an analytic sensitivity for minor
      alleles of <20%, in particular, when assessing the mutational status of
      heterogeneous tumor samples. Here, we describe a simple modification to the FTSS
      workflow that improves the limit of detection of cell-line gDNA mixtures from 50%
      20% to 5% for G>A transitions and from 50%-5% to 5% for G>C and G>T
      transversions. In addition, we use two different sample types to compare the
      limit of detection of sequence variants in codons 12 and 13 of the KRAS gene
      between Sanger sequencing and other methodologies including shifted termination
      assay (STA) detection, single-base extension (SBE), pyrosequencing (PS), high-
      resolution melt (HRM), and real-time PCR (qPCR).

PMID- 22963482
TI  - Accounting for uncertainty in model-based prevalence estimation: paratuberculosis
      control in dairy herds.
AB  - BACKGROUND: A common approach to the application of epidemiological models is to
      determine a single (point estimate) parameterisation using the information
      available in the literature. However, in many cases there is considerable
      uncertainty about parameter values, reflecting both the incomplete nature of
      current knowledge and natural variation, for example between farms. Furthermore
      model outcomes may be highly sensitive to different parameter values.
      Paratuberculosis is an infection for which many of the key parameter values are
      poorly understood and highly variable, and for such infections there is a need to
      develop and apply statistical techniques which make maximal use of available
      data. RESULTS: A technique based on Latin hypercube sampling combined with a
      novel reweighting method was developed which enables parameter uncertainty and
      variability to be incorporated into a model-based framework for estimation of
      prevalence. The method was evaluated by applying it to a simulation of
      paratuberculosis in dairy herds which combines a continuous time stochastic
      algorithm with model features such as within herd variability in disease
      development and shedding, which have not been previously explored in
      paratuberculosis models. Generated sample parameter combinations were assigned a
      weight, determined by quantifying the model's resultant ability to reproduce
      prevalence data. Once these weights are generated the model can be used to
      evaluate other scenarios such as control options. To illustrate the utility of
      this approach these reweighted model outputs were used to compare standard test
      and cull control strategies both individually and in combination with simple
      husbandry practices that aim to reduce infection rates. CONCLUSIONS: The
      technique developed has been shown to be applicable to a complex model
      incorporating realistic control options. For models where parameters are not well
      known or subject to significant variability, the reweighting scheme allowed
      estimated distributions of parameter values to be combined with additional
      sources of information, such as that available from prevalence distributions,
      resulting in outputs which implicitly handle variation and uncertainty. This
      methodology allows for more robust predictions from modelling approaches by
      allowing for parameter uncertainty and combining different sources of
      information, and is thus expected to be useful in application to a large number
      of disease systems.

PMID- 22963483
TI  - DPP-4 inhibition attenuates cardiac dysfunction and adverse remodeling following
      myocardial infarction in rats with experimental diabetes.
AB  - AIMS: Following myocardial infarction (MI), individuals with diabetes have a two
      fold increase in the risk of heart failure, due in part to excessive loss of
      cardiac microvasculature. Endothelial integrity and restitution are mediated in
      part by stromal cell-derived factor-1alpha (SDF-1alpha), a chemokine that is
      elaborated by ischemic tissue but rapidly degraded by dipeptidyl peptidase-4 (DPP
      4). Accordingly, we hypothesized that inhibiting this enzyme may confer benefit
      following myocardial infarction in the diabetic setting beyond its effect on
      glycemia. METHODS AND RESULTS: Fischer F344 rats with streptozotocin (STZ)
      diabetes were randomized to receive vehicle or the DPP-4 inhibitor, sitagliptin
      (300 mg/kg/day). Two weeks later, animals underwent experimental MI, induced by
      ligation of the left anterior descending coronary artery. Cardiac function was
      assessed by conductance catheterization and echocardiography along with cardiac
      structure 4 weeks post-MI. Following MI, untreated diabetic rats developed both
      systolic and diastolic cardiac dysfunction, in association with endothelial cell
      loss, fibrosis, and myocyte hypertrophy. Without affecting plasma glucose,
      sitagliptin treatment led to an improvement in passive left ventricular
      compliance, increased endothelial cell density, reduced myocyte hypertrophy, and
      a reduction in the abundance of collagen 1 (all P < 0.05). Systolic function was
      unchanged. CONCLUSIONS: This study shows that DPP-4 inhibition attenuates
      several, but not all, aspects of cardiac dysfunction and adverse remodeling in
      the post-MI setting.

PMID- 22963484
TI  - Quantitative double antibody sandwich ELISA for the determination of gliadin.
AB  - A sensitive double antibody sandwich ELISA (DAS-ELISA) based on chicken anti
      gliadin IgY and biotinylated monoclonal antibody (mAb) was developed for the
      quantification of gliadin in foods. The anti-gliadin IgY and mAb specifically
      detected gliadin in wheat, barley, and rye by indirect ELISA and Western-blot
      assay. Using anti-gliadin IgY as capture antibody and biotinylated mAb as
      detecting antibody, the sensitivity of DAS-ELISA has a linear standard range of 4
      40 ng/mL, showing that the limit of detection (LOD) corresponds to 4 ng/mL
      gliadin in assay buffer, equivalent to 0.8 ppm in foods. The intra-assay
      expressed as percentage of coefficients of variation (%CV) was 7.25% average of
      six food samples. The interassay precision was 9.51% in food samples. The
      combination of anti-gliadin IgY and biotinylated mAb in the DAS-ELISA provides a
      reliable, sensitive, and inexpensive tool for the detection of gliadin in gluten
      free and gluten-containing food products.

PMID- 22963485
TI  - Expression, purification, and characterization of RGD-mda-7, a His-tagged mda
      7/IL-24 mutant protein.
AB  - RGD peptide (Arg-Gly-Asp tripeptide) binds to integrin alphaVbeta(3) and
      alphaVbeta(5), which is selectively expressed in tumor neovasculature and on the
      surface of some tumor cells. Some studies showed that coupling the RGD peptides
      to anticancer drugs yielded compounds with increased efficiency against tumors
      and lowered toxicity to normal tissues. The melanoma differentiation-associated
      gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine
      gene that exhibits potent tumor-suppressive activity without damaging normal
      cells. To enhance the antitumor effect, we inserted a glycine residue into the
      wild type (mda-7/IL-24) between (164)Arg and (165)Asp to form a RGD peptide,
      named RGD-mda-7, then expressed RGD-mda-7 in Escherichia coli. Herein, we
      describe the expression and purification of RGD-mda-7. We detected the
      characterizations of immunostimulatory activity, tumor targeting, potent
      cytopathic effect, and apoptosis inducing exploited by RGD-mda-7 in tumor cells,
      and also compared these characterizations with wtmda-7/IL-24. The data showed
      that RGD-mda-7 had more potent tumor targeting and apoptosis-inducing effects
      than wtmda-7/IL-24.

PMID- 22963486
TI  - Analysis of naturally occurring zearalenone in feeding stuffs and urine of farm
      animals in Croatia.
AB  - The aim of this study was to determine feed and urinary levels of zearalenone. A
      total of 114 samples, 64 feeding stuffs (commodities, pig and cattle feed), and
      50 urine samples were analyzed by the use of enzyme-linked immunosorbent assay
      (ELISA). Zearalenone was detected in 68.7% of feeding stuffs, while all urine
      samples except for four yearling samples were positive for zearalenone. The
      maximum zearalenone concentration in feeding stuffs and urine was 577 ng/g and
      241.1 ng/mL, respectively. Although zearalenone concentrations in some samples
      were high, the risk for humans was negligible since the calculated concentrations
      in meat were below the tolerable daily intake (TDI).

PMID- 22963487
TI  - Application of immunomagnetic particles to enzyme-linked immunosorbent assay
      (ELISA) for improvement of detection sensitivity of HCG.
AB  - This investigation was aimed at using superparamagnetic particles to enzyme
      linked immunosorbent assay (SPIO-ELISA) of human chorionic gonadotropin (hCG) to
      enhance detection sensitivity of hCG. We found that N-(3-dimethyl aminopropyl)-N'
      ethylcarbodiimide hydrochloride (EDC) was the best cross-linking reagent to link
      anti hCG alpha antibody to superparamagnetic particle (SPIO-anti hCG alpha
      antibody immunomagnetic particle). To improve the specificity of the assay, a
      horse radish peroxidase (HRP)-labeled anti-hCG beta monoclonal antibody was used
      to detect captured hCG using double antibody sandwich ELISA assay. SPIO-ELISA
      application to determine hCG increased the sensitivity to 1 mIU/mL, which is a
      level of sensitivity enabling the diagnosis of pregnancy during the early
      gestational period.

PMID- 22963488
TI  - Immunomodulatory activity of the water extract of Thymus vulgaris, Thymus
      daenensis, and Zataria multiflora on dendritic cells and T cells responses.
AB  - Thymus vulgaris (thyme), Thymus daenensis, and Zataria multiflora are medicinal
      plants being used widely for infections and inflammatory diseases in folk
      medicine. In this study, the effects of the water extract of these plants on the
      activation of dendritic cells (DCs) and T cells was investigated. Both T.
      vulgaris and Z. multiflora decreased the proliferation of mitogen-stimulated
      lymphocytes, whereas T. daenensis induced cell proliferation in a dose-dependent
      manner (p < 0.001). All the three plants increased the CD40 expression on DCs (p
      < 0.04). The extent of allogenic T cell proliferation in the presence of T.
      vulgaris and Z. multiflora extracts was significantly decreased (p < 0.02). The
      effect of the extracts on secretion of IFN-gamma and IL-4 cytokines showed that
      none of the extracts influenced the pattern of cytokine production by T helper
      (Th) cells toward a Thl or Th2 profile. In conclusion, all the extracts had the
      ability to activate DCs. Whereas Z. multiflora and T. vulgaris extracts showed
      immunoihibitory effects on allogenic T cell proliferation, the main effect of T.
      daenensis was on mitogenic T cell response. These data may partly explain the
      mechanisms underlying the beneficial immunomodulatory effects of these extracts
      in infections and immune-related diseases.

PMID- 22963489
TI  - Development of quantitative receptor-ligand binding assay for use as a tool to
      estimate immune responses against Plasmodium vivax Duffy binding protein Region
      II.
AB  - Antibodies generated against Region II of Plasmodium vivax Duffy binding protein
      (PvRII) can block binding of this parasite ligand to its receptor, the Duffy
      antigen receptor for chemokines (DARC), and prevent erythrocyte infection by the
      parasite. An in vitro functional assay that can serve as an immune correlate of
      an antigen activity is an important tool to guide vaccine development. We
      describe here the development of a quantitative binding assay and its use to
      study immune responses against PvRII. The assay was used to test anti-PvRII mouse
      sera, and was found a useful tool for quantitative estimation of anti-PvRII
      blocking antibodies.

PMID- 22963490
TI  - Correlation of deoxynivalenol and fumonisin concentration determined in maize by
      ELISA methods.
AB  - Maize (Zea mays) is one of the most common crops in Croatia that is often
      contaminated with mycotoxins. The enzyme linked immunosorbent assay (ELISA)
      method as a screening immunological method has become very popular in the
      determination of mycotoxins contamination of cereals, as it has many advantages
      such as a rapid and simple determination of their concentration. In this present
      study, 40 maize samples collected from animal feed factories were analyzed for
      the concentration of deoxynivalenol (DON) and fumonisin (FUM) using the validated
      ELISA method of two different kit manufacturers to investigate the correlation of
      the determined mycotoxins concentration. The correlation coefficients for the
      concentration of DON and FUM, obtained using different kit manufacturers, were r
      = 0.9698 and r = 0.9303, respectively, yielding a high correlation between the
      applied ELISA methods. Concerning the legislation, in one maize sample, the DON
      concentration higher than the maximum recommended value was determined (16.24
      mg/kg), whereas the FUM concentration in all the analyzed samples, without
      exception, were in accordance with recommended values.

PMID- 22963491
TI  - Characterization and enzyme-conjugation of a specific anti-L1 nanobody.
AB  - Persistent infection of the human papillomaviruses (HPV) has been shown to result
      in cervical cancer and intraepithelial neoplasia. Early detection and screening
      programs are essential strategies against cervical cancer. A nanobody is the
      smallest antigen-binding fragment known and is derived from a camelid heavy-chain
      antibody. This tiny protein shows high solubility and stability. It can be
      produced cost-effectively with high yield production. In this study, we enriched
      a nanobody library against the L1 protein of HPV. Several colons were selected
      from this enriched library using monoclonal phage-enzyme linked immunosorbent
      assay (phage-ELISA) and analyzed for identification of nanobody genes. The
      expression of nanobody fragments was performed in Rosetta gami2. The C74 nanobody
      that showed strong binding to the L1 protein of HPV16 was selected, purified, and
      characterized by Western blotting and ELISA. The selected nanobody was tested for
      sensitivity, specificity, and affinity. A nanobody conjugated to horseradish
      peroxidase (HRP) was selected and used for detection of L1 protein of HPV16. This
      study demonstrates that the C74-HRP, due to its specificity and good binding
      affinity for a specific viral antigen, is a potential diagnostic tool that can be
      used as a promising reagent for the new generation of HPV diagnosis approaches.

PMID- 22963492
TI  - Method comparison for CA 15-3, CA 19-9, and CA 125 determination using the new
      LOCI technique of Dimension Vista 1500 and Immulite 2000 XPI.
AB  - We performed method comparison for the tumor markers CA 15-3, CA 19-9, and CA 125
      measured by luminescent oxygen channeling immunoassay technology on the Dimension
      Vista 1500 and by classic luminescence technology on the Immulite 2000 XPI.
      Within-day and total imprecision were determined according to Clinical and
      Laboratory Standards Institute (CLSI) guidelines using three serum pools at
      different clinically relevant levels. In addition, parallel measurements on both
      systems were performed in a total of 738 routine serum samples (133 CA 15-3, 395
      CA 19-9, and 210 CA 125). Total imprecision of serum pools for CA 15-3 ranged
      between 4.6% and 5.9%, for CA 19-9 between 4.4% and 7.8%, and for CA 125 between
      3.3% and 4.3%. Marker values determined within the measurement range of both
      systems correlated well with each other (R = 0.88 for CA 15-3, R = 0.93 for CA 19
      9, and R = 0.96 for CA 125). Slopes between the Vista and the Immulite method
      were 0.96 for CA 125, 0.72 for CA 15-3, and 0.87 for CA 19-9, indicating lower
      values for CA 15-3 and CA 19-9 when measured by the Vista method. This was
      particularly obvious for CA 19-9 levels in the lower measuring range of <100 U/mL
      (R = 0.85; slope 0.73).

PMID- 22963494
TI  - Low--molecular weight heparins and unfractionated heparins during primary
      coronary intervention.
AB  - Coronary artery diseases continue to be the most common causes of mortality and
      morbidity in the industrialized world, especially in the setting of acute
      myocardial infarction. Anticoagulation during primary percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI) has
      traditionally been supported by anticoagulant unfractionated heparin (UFH).
      Recently, alternative anticoagulants such as low molecular weight heparin (LMWH)
      were included in the management of STEMI. The aim of the present review is to
      compare efficacy and safety outcomes among patients receiving low molecular
      weight heparins (LMWH) or unfractionated heparin (UFH) while undergoing PCI for
      STEMI.

PMID- 22963495
TI  - Pharmacological adjuvant therapies in primary coronary interventions:
      bivalirudin.
AB  - The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular
      medicine over the past decade because, in comparison with unfractionated heparin,
      it guarantees a predictable dose-related degree of anticoagulation with a low
      immunogenic profile and, possibly, with reduced rates of major bleeding
      complications. In the past bivalirudin has been frequently employed in the
      management of patients with heparin-induced thrombocytopenia. The REPLACE-2,
      ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in
      comparison with unfractionated heparin in terms of ischemic end-points with a
      reduction of the bleeding rate also in patients acute coronary syndrome without
      ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug
      as a first choice anticoagulant during percutaneous coronary interventions in
      patients with ST-elevation myocardial infarction. In fact the bivalirudin alone
      regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased in
      hospital bleeding rates and short and long term mortality. Given the body of
      clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the
      leading place among the proposed anticoagulation strategies in the setting of
      acute coronary syndromes. The duration of the bivalirudin infusion after PCI and
      the optimal oral antiplatelet regimen associated to bivalirudin are important
      issues to be solved in future randomized controlled studies.

PMID- 22963496
TI  - Pharmacotherapy during percutaneous coronary intervention in acute myocardial
      infarction.

PMID- 22963498
TI  - The functions of worry and its relation to performance in controllable and
      uncontrollable situations.
AB  - The current study addressed the functions of worry in controllable and
      uncontrollable stressful situations, with the purpose of testing the "truth"
      behind positive beliefs about worry. All participants (N=72) were immersed in a
      stressful situation, that of delivering a speech in front of a camera, and they
      were randomly allocated to two experimental conditions; in the controllable
      situation, participants knew the topic in advance, whereas in the uncontrollable
      situation, they had to give an impromptu speech. Worry was negatively associated
      with performance in the controllable, r(36) = -.469, p=.002, but not in the
      uncontrollable condition, r(34) = -.106, p>.05, and, for the participants who
      believed in the benefits of worry, worrying was not positively related to
      performance, r(32) = -.196, p>.05. Therefore, it appears that in stressful
      situations, worrying is not associated with increased performance, even if people
      might believe in its benefits.

PMID- 22963497
TI  - A novel reproductive peptide, phoenixin.
AB  - Normal anterior pituitary function is essential for fertility. Release from the
      gland of the reproductive hormones luteinising hormone and follicle-stimulating
      hormone is regulated primarily by hypothalamically-derived gonadotrophin
      releasing hormone (GnRH), although other releasing factors (RF) have been
      postulated to exist. Using a bioinformatic approach, we have identified a novel
      peptide, phoenixin, that regulates pituitary gonadotrophin secretion by
      modulating the expression of the GnRH receptor, an action with physiologically
      relevant consequences. Compromise of phoenixin in vivo using small interfering
      RNA resulted in the delayed appearance of oestrus and a reduction in GnRH
      receptor expression in the pituitary. Phoenixin may represent a new class of
      hypothalamically-derived pituitary priming factors that sensitise the pituitary
      to the action of other RFs, rather than directly stimulating the fusion of
      secretary vesicles to pituitary membranes.

PMID- 22963499
TI  - Commissural mitral regurgitation detected by abnormal blood flow pattern in the
      left atrial appendage.
AB  - An 86-year-old man with severe symptomatic aortic stenosis underwent an aortic
      valve replacement. A transesophageal echocardiogram (TEE) was performed during
      the surgery and demonstrated mild mitral regurgitation (MR). The patient's
      symptoms persisted despite surgery, and subsequent TEE demonstrated prolapse of
      the posteromedial commissural leaflet, with evidence of a severe, very eccentric
      MR jet which was directed laterally and superiorly. The jet was almost missed in
      most imaging planes and could finally be exposed by withdrawing the probe to the
      level of the aortic valve and left atrial appendage. 

PMID- 22963501
TI  - Respiratory syncytial virus infection differentiates airway dysfunction in the
      central and peripheral airways in OVA-sensitized mice.
AB  - Much evidence suggests that respiratory syncytial virus (RSV) infection prolongs
      airway hyperresponsiveness (AHR) and exacerbates asthma by enhancing airway
      inflammation. However, the characteristic of airway inflammation and kinetics of
      airway dysfunction occurred in the central and peripheral airways were not fully
      delineated. The objective of this study was to investigate the effect of RSV on
      the allergic airway inflammation in different size airways and to elucidate its
      possible mechanism. Using a murine model of prior ovalbumin (OVA) sensitization
      and subsequent RSV challenge, lung resistance (R(L)), and dynamic compliance
      (Cdyn) was conducted by barometric whole-body plethysmography. Histological
      examinations were carried out. Differential cells count in bronchoalveolar lavage
      (BAL) fluid, serum anti-OVA IgE, and IgG1 were measured. Cytokine mRNA expression
      in lung tissue were determined. RSV triggered a significant increase in R(L) and
      reduction in Cdyn, as well as greatly prolonged the recovery of Cdyn more than
      that of R(L) in OVA-sensitized mice. Also, RSV resulted in more severe peripheral
      airway inflammation which exhibit as globe cell hyperplasia and CD8+ T cell
      infiltration. Furthermore, the number of lymphocytes, neutrophils and macrophages
      in BAL fluid, serum anti-OVA IgE and IgG1 were remarkably increased.
      Additionally, mice increased relative expression of cytokines IL-4, IL-13, and
      IFN-gamma, but not IL-5, IL-17, and IL-17F. These findings demonstrated that RSV
      could selectively affect pathologic processes that contribute to altered airway
      function in the central and peripheral airways in OVA-sensitized mice. These
      processes may be involved in goblet cell hyperplasia and CD8+ T cell infiltration
      in peripheral airways.

PMID- 22963500
TI  - Reverse translation of phase I biomarker findings links the activity of
      angiotensin-(1-7) to repression of hypoxia inducible factor-1alpha in vascular
      sarcomas.
AB  - BACKGROUND: In a phase I study of angiotensin-(1-7) [Ang-(1-7)], clinical benefit
      was associated with reduction in plasma placental growth factor (PlGF)
      concentrations. The current study examines Ang-(1-7) induced changes in
      biomarkers according to cancer type and investigates mechanisms of action engaged
      in vitro. METHODS: Plasma biomarkers were measured prior to Ang-(1-7)
      administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for
      interaction were performed to determine the impact of cancer type on angiogenic
      hormone levels. If a positive interaction was detected, treatment-induced
      biomarker changes for individual cancer types were assessed. To investigate
      mechanisms of action, in vitro growth assays were performed using a murine
      endothelioma cell line (EOMA). PCR arrays were performed to identify and
      statistically validate genes that were altered by Ang-(1-7) treatment in these
      cells. RESULTS: Tests for interaction controlled for dose cohort and clinical
      response indicated a significant impact of cancer type on post-treatment VEGF and
      PlGF levels. Following treatment, PlGF levels decreased over time in patients
      with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1
      7) led to significant growth suppression at doses as low as 100 nM. PCR arrays
      identified 18 genes that appeared to have altered expression after Ang-(1-7)
      treatment. Replicate analyses confirmed significant changes in 8 genes including
      reduction in PlGF (P = .04) and hypoxia inducible factor 1alpha (HIF-1alpha)
      expression (P < .001). CONCLUSIONS: Ang-(1-7) has clinical and pre-clinical
      activity for vascular sarcomas that is linked to reduced HIF-1alpha and PlGF
      expression.

PMID- 22963502
TI  - Preparation and application of patterned membranes for wastewater treatment.
AB  - Membrane fouling remains a critical factor limiting the widespread use of
      membrane processes in water and wastewater treatment. To mitigate membrane
      fouling, we introduced a patterned morphology on the membrane surface using a
      lithographic method. A modified immersion precipitation method was developed to
      relieve the formation of dense layer at the solvent-nonsolvent interface, that
      is, the opposite side of the patterned surface. Diverse patterned membranes, such
      as pyramid-, prism-, and embossing-patterned membranes, were prepared and
      compared with a flat membrane in terms of morphology, permeability, and
      biofouling. Patterned membrane fidelity was largely dependent on the polymer
      concentration in cast solution. The patterned surface augmented the water flux in
      proportion to the roughness factor of the patterned membrane. However, the type
      of pattern did not affect substantially the mean pore size on the patterned
      surface. Deposition of microbial cells on the patterned membrane was
      significantly reduced compared to that on the flat membrane in the membrane
      bioreactor (MBR) for wastewater treatment. This was attributed to hydraulic
      resistance of the apex of the patterned surface, which induced local turbulence.

PMID- 22963504
TI  - Nephrotic syndrome and acute tubular necrosis due to meloxicam use.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by patients all
      over the world. Five to eighteen percent of the patients who receive NSAIDs can
      suffer from kidney-related side effects. Among them, the most relevant are sodium
      and water retention, hyponatremia, worsening of hypertension or preexisting
      cardiac failure, hyperkalemia, acute kidney injury, chronic kidney disease,
      papillary necrosis, nephrotic syndrome (NS), and acute interstitial nephritis. We
      report the case of a 65-year-old woman who developed acute tubular necrosis and
      NS a few days after receiving 15 mg of meloxicam (MLX) for 3 days for tendinitis.
      Steroid therapy was begun with normalization of kidney function after 7 weeks of
      treatment. NS (minimal change disease) was characterized by frequent remissions
      and relapses as prednisone was lowered under 30 mg/day. Azathioprine (100 mg/day)
      was added on the fifth month of diagnosis and a complete remission was finally
      obtained 4 years after hospital admittance. In her last medical checkup, 8 years
      after her debut and receiving azathioprine (50 mg) and prednisone (5 mg/day),
      renal function was normal (creatinine 1.0 mg/dL and creatinine clearance 80
      mL/min/1.73 m(2)), proteinuria was 150 mg/day and there was no hematuria or
      hypertension.   The aim of communicating this case is to raise a warning about
      these renal side effects of MLX. After thorough review of literature, only one
      other report with the same findings was found.

PMID- 22963503
TI  - Enhancement of object detection with transcranial direct current stimulation is
      associated with increased attention.
AB  - BACKGROUND: We previously found that Transcranial Direct Current Stimulation
      (tDCS) improves learning and performance in a task where subjects learn to detect
      potential threats indicated by small target objects hidden in a complex virtual
      environment. In the present study, we examined the hypothesis that these effects
      on learning and performance are related to changes in attention. The effects of
      tDCS were tested for three forms of attention (alerting, orienting, and executive
      attention) using the Attention Network Task (ANT), which were compared with
      performance on the object-learning task. RESULTS: Participants received either
      0.1 mA (N = 10) or 2.0 mA (N = 9) tDCS during training and were tested for
      performance in object-identification before training (baseline-test) and again
      immediately after training (immediate test). Participants next performed the
      Attention Networks Task (ANT), and were later tested for object-identification
      performance a final time (delayed test). Alerting, but not orienting or executive
      attention, was significantly higher for participants receiving 2.0 mA compared
      with 0.1 mA tDCS (p < 0.02). Furthermore, alerting scores were significantly
      correlated with the proportion of hits (p < 0.01) for participants receiving 2.0
      mA. CONCLUSIONS: These results indicate that tDCS enhancement of performance in
      this task may be related in part to the enhancement of alerting attention, which
      may benefit the initial identification, learning and/or subsequent recognition of
      target objects indicating potential threats.

PMID- 22963505
TI  - HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples
      suspicious for mycobacterial infections.
AB  - Various molecular methods have been used for the rapid identification of
      mycobacterial species. In this survey, evaluation of antibiotic resistance and
      PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was
      carried out for identification of non-tuberculosis mycobacteria (NTM) isolates
      from different clinical specimens. Forty-eight different mycobacterial isolates
      were selected and followed by the conventional and PRA of hsp65 for species
      identification. The antibiotic susceptibility test was carried out according to
      standard methods. A 439 bp PCR product of hsp65 in all selected isolates was
      amplified and digested with the BstEII and HaeIII restriction enzymes. The
      restriction fragment length polymorphism (RFLP) patterns were analyzed for
      species identification. Using PRA for 48 mycobacterial selected isolates,
      including 15 M. tuberculosis, one M. bovis and all 32 isolates of NTM, revealed
      11 different species among the NTM isolates. The most frequent NTM isolates were
      M. kansasii, M. gordonae III, M. marinum, M. chelonae, M. scrofluaceum and M.
      gastri. In most cases, the PRA results were perfectly in accordance with the
      classical biochemical method. Combination of resistance to rifampin and isoniazid
      was present among M. kansasi, M. gordoniae III, M. scrofluaceum, M. chelonae, M.
      marinum, M. gastri, M. gordoniae II and M. trivale isolates. A high incidence of
      co-resistance to six, five, four and three anti-TB drugs was observed in 18.5%,
      9.1%, 6.6% and 11.7% of all NTM isolates, respectively. Our results showed that
      PRA, in comparison with classical methods, is rapid and accurate enough for the
      identification of mycobacterial species from LJ medium. Additionally, we found
      that in Iran we have a highly diverse population of NTM isolates among patients
      suspected of having TB.

PMID- 22963506
TI  - Does spironolactone have a dose-dependent effect on left ventricular remodeling
      in patients with preserved left ventricular function after an acute myocardial
      infarction?
AB  - AIMS: The aim of this study was to investigate the effects of spironolactone on
      left ventricular (LV) remodeling in patients with preserved LV function following
      acute myocardial infarction (AMI). METHODS AND RESULTS: Successfully
      revascularized patients (n = 186) with acute ST elevation MI (STEMI) were
      included in the study. Patients were randomly divided into three groups, each of
      which was administered a different dose of spironolactone (12.5, 25 mg, or none).
      Echocardiography was performed within the first 3 days and at 6 months after MI.
      Echocardiography control was performed on 160 patients at a 6-month follow-up.
      The median left ventricular ejection fraction (LVEF) increased significantly in
      all groups, but no significant difference was observed between groups (P = 0.13).
      At the end of the sixth month, the myocardial performance index (MPI) had
      improved in each of the three groups, but no significant difference was found
      between groups (F = 2.00, P = 0.15). The mean LV peak systolic velocities (Sm )
      increased only in the control group during the follow-up period, but there is no
      significant difference between groups (F = 1.79, P = 0.18). The left ventricular
      end-systolic volume index (LVESVI) and the left ventricular end-diastolic volume
      index (LVEDVI) did not change significantly compared with the basal values
      between groups (F = 0.05, P = 0.81 and F = 1.03, P = 0.31, respectively).
      CONCLUSION: In conclusion, spironolactone dosages of up to 25 mg do not augment
      optimal medical treatment for LV remodeling in patients with preserved cardiac
      functions after AMI.

PMID- 22963507
TI  - Transfer of the coccidiostats monensin and lasalocid from feed at cross
      contamination levels to whole egg, egg white and egg yolk.
AB  - Recent legislation has addressed the unavoidable carry-over of coccidiostats and
      histomonostats in feed, which may lead to the presence of residues of these
      compounds in eggs. In this study, laying hens received cross-contaminated feed at
      a ratio of 2.5%, 5% and 10% of the therapeutic dose of monensin and lasalocid for
      broilers. The eggs were collected during the treatment and depletion period and
      were analysed using liquid chromatography-tandem mass spectrometry. The different
      egg matrices were separated and analysed during the plateau phase. High lasalocid
      concentrations, which exceeded the maximum residue level, and low monensin
      concentrations were found in whole egg. Plateau levels were reached at days 7-9
      for lasalocid and at days 3-5 for monensin. For lasalocid, the highest
      concentrations were measured in egg yolk; residue concentrations in egg white
      were very low.

PMID- 22963508
TI  - Structure and mechanical properties of human trichocyte keratin intermediate
      filament protein.
AB  - Keratin is a protein in the intermediate filament family and the key component of
      hair, nail, and skin. Here we report a bottom-up atomistic model of the keratin
      dimer, using the complete human keratin type k35 and k85 amino acid sequence. A
      detailed analysis of geometric and mechanical properties through full-atomistic
      simulation with validation against experimental results is presented. We
      introduce disulfide cross-links in a keratin tetramer and compare the mechanical
      behavior of the disulfide bonded systems with a system without disulfide bonds.
      Disulfide bond results in a higher strength (20% increase) and toughness (49%
      increase), but the system loses alpha-helical structures under loading,
      suggesting that disulfide bonds play a significant role in achieving the
      characteristic mechanical properties of trichocyte alpha-keratin. Our study
      provides general insight into the effect of disulfide cross-link on mechanical
      properties. Moreover, the availability of an atomistic model of this protein
      opens the possibility to study the mechanical properties of hair fibrils and
      other fibers from a bottom-up perspective.

PMID- 22963510
TI  - Hollow interior structure of spin-coated polymer thin films revealed by ToF-SIMS
      three-dimensional imaging.
AB  - Surface patterns were observed on spin-coated poly(bisphenol A decane ether) (BA
      C10) films prepared with chloroform and tetrahydrofuran as the solvents. The
      interior structure of these surface patterns were analyzed using a time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) equipped with a bismuth cluster source
      for ion imaging and a C(60)(+) cluster source for depth profiling. For the first
      time, the surface patterns have been shown to be hollow rather than solid using
      ToF-SIMS three-dimensional (3D) analysis and optical techniques. Moreover, the
      microarea depth profiling analysis indicated that the hollow structure was
      sandwiched between two polymer layers rather than sitting on the substrate. The
      height of the hollow structure and the thicknesses of the polymer layers above
      and below the hollow structure were also estimated from the depth profiling
      results.

PMID- 22963509
TI  - Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and
      umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound
      study.
AB  - BACKGROUND: During early pregnancy, the placenta develops to meet the metabolic
      demands of the foetus. The objective of this analysis was to examine the effect
      of malaria parasitaemia prior to 20 weeks' gestation on subsequent changes in
      uterine and umbilical artery blood flow and intrauterine growth restriction.
      METHODS: Data were analysed from 548 antenatal visits after 20 weeks' gestation
      of 128 women, which included foetal biometric measures and interrogation of
      uterine and umbilical artery blood flow. Linear mixed effect models estimated the
      effect of early pregnancy malaria parasitaemia on uterine and umbilical artery
      resistance indices. Log-binomial models with generalized estimating equations
      estimated the effect of early pregnancy malaria parasitaemia on the risk of
      intrauterine growth restriction. RESULTS: There were differential effects of
      early pregnancy malaria parasitaemia on uterine artery resistance by nutritional
      status, with decreased uterine artery resistance among nourished women with early
      pregnancy malaria and increased uterine artery resistance among undernourished
      women with early pregnancy malaria. Among primigravidae, early pregnancy malaria
      parasitaemia decreased umbilical artery resistance in the late third trimester,
      likely reflecting adaptive villous angiogenesis. In fully adjusted models,
      primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of
      subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the
      referent group of multigravidae with no early pregnancy malaria parasitaemia.
      CONCLUSIONS: Early pregnancy malaria parasitaemia affects uterine and umbilical
      artery blood flow, possibly due to alterations in placentation and angiogenesis,
      respectively. Among primigravidae, early pregnancy malaria parasitaemia increases
      the risk of intrauterine growth restriction. The findings support the initiation
      of malaria parasitaemia prevention and control efforts earlier in pregnancy.

PMID- 22963511
TI  - Total joint replacement in men: old age, obesity and in-hospital complications.
AB  - BACKGROUND: We assessed risks of incident in-hospital complications and 1-year
      and 5-year mortality following elective primary total joint replacement (TJR),
      focusing on obesity. METHODS: Longitudinal data from a population-based cohort of
      819 men who had had TJR were integrated with validated hospital morbidity data
      and mortality records. Complications recorded in the index admission were
      classified as major or minor by 13 independent orthopaedic surgeons. RESULTS: Of
      819 men (mean age 76.3 (SD 4.5) years), 331 patients (40.4%) had an in-hospital
      complication from whom 155 (18.9%) had at least one major complication that was
      classified as potentially life threatening. Obesity and age were independently
      associated with increased risk of major complications. Compared with patients
      without complications, those with major complications experienced significantly
      greater mortality in 1 year (5.8% versus 1.2%, P = 0.001) and 5 years (16.8%
      versus 8.0%, P = 0.002) following TJR. In Cox regressions, age, Charlson Co
      morbidity index and major complications were independently associated with 1-year
      mortality. Age and Charlson Co-morbidity index were also associated with 5-year
      mortality. Similarly, risk of dying within 5 years of TJR was higher among
      patients with class II obesity compared with patients with normal weight. The
      most frequently reported complications were those in the cardio-respiratory and
      general systems. Complications in the cardio-respiratory system significantly
      increased hazard of 1- and 5-year mortality. CONCLUSION: The elderly and the
      obese are more likely to develop adverse outcomes following a primary TJR. Our
      findings may assist clinicians in better selecting elderly patients for surgery,
      and informing them about their individual level of risk.

PMID- 22963512
TI  - Simulating the interaction between amino acids and DNA: a combined matrix
      isolation FT-IR and theoretical study of the 1-methyluracil.glycine H-bond
      complexes using a dual sublimation furnace.
AB  - The H-bond complex formation between 1-methyluracil and glycine has been
      investigated by theoretical calculations and the most stable complex
      configurations have been identified by FT-IR spectroscopy in Ar matrices. The
      importance of this H-bonding system is huge since all DNA biological functions
      are dependent on the interactions with proteins. The theoretical optimizations
      have revealed six different closed H-bond complexes between 1-methyluracil and
      glycine. The obtained energies have demonstrated that the uracil C(4)?O site is a
      better H-acceptor site than the C(2)?O site. The stabilization energy of the most
      stable complex is -47.83 (MP2) or -54.14 kJ.mol(-1) (DFT). The DFT(B3LYP)/6-31G
      optimized geometries have been evaluated, and the obtained energies appeared to
      be in agreement with the results of the computational more expensive DFT(B3LYP)6
      31++G** approach. In order to identify the 1:1 complexes in an argon matrix, a
      new dual miniature furnace has been developed which allows to sublimate both
      complex partners at their optimal temperature. The presence of three different
      glycine.1-methyluracil complexes has been demonstrated by analysis of the H-bond
      shifted modes. The H-bond parameters have been evaluated and previously obtained
      correlations for different H-bond complexes have been confirmed.

PMID- 22963513
TI  - Ready to rumble: how team personality composition and task conflict interact to
      improve performance.
AB  - Although prior work has proposed a number of conditions under which task conflict
      in teams may improve performance, composition variables have been left
      unexplored. Given the effects of personality traits on team processes and
      outcomes demonstrated in prior work, investigating whether specific personality
      compositions influence the effect of task conflict on team performance is
      critical to researchers' understanding of conflict in teams. Our results indicate
      that team-level averages of both openness to experience and emotional stability
      function as moderators of the relationship between task conflict and team
      performance. Specifically, task conflict had a positive impact on performance in
      teams with high levels of openness or emotional stability; in contrast, task
      conflict had a negative impact on performance in teams with low levels of
      openness or emotional stability. Thus, when task conflict emerges, teams composed
      of members who are open minded or emotionally stable are best able to leverage
      conflict to improve performance. Implications for theory and practice are
      discussed.

PMID- 22963514
TI  - When is success not satisfying? Integrating regulatory focus and
      approach/avoidance motivation theories to explain the relation between core self
      evaluation and job satisfaction.
AB  - Integrating implications from regulatory focus and approach/avoidance motivation
      theories, we present a framework wherein motivational orientations toward
      positive (approach motivation orientation) or negative (avoidance motivation
      orientation) stimuli interact with workplace success to mediate the relation of
      core self-evaluation (CSE) with job satisfaction. Using data collected from
      supervisor-subordinate dyads (Sample 1) and time-lagged data (Sample 2), we found
      that the results from two studies indicated that the interaction of workplace
      success and avoidance motivation orientation mediated relations of CSE with job
      satisfaction. Although approach motivation orientation did not interact with
      workplace success, it did mediate the CSE-job satisfaction relation on its own.
      Implications for the CSE and approach/avoidance literatures are discussed.

PMID- 22963515
TI  - Polarity-mismatched addition of electrophilic carbon radicals to an electron
      deficient acceptor: cascade radical addition-cyclization-trapping reaction.
AB  - The polarity-mismatched perfluoroalkyl radical addition to electron-deficient
      alkenes was studied. For this study, several substrates having two polarity
      different radical acceptors were employed to investigate the regiochemical
      courses of cascade reaction. In the case of substrate 1 having a methacryloyl
      moiety, we found polarity-mismatched perfluoroalkylation giving 15a-e as a major
      course over the polarity-matched perfluoroalkylation giving 16a-e. Moreover, in
      the case of substrates 2-7, perfluoroalkyl radicals selectively added to an
      electron-deficient alkene moiety of 2-7, to give polarity-mismatched
      perfluoroalkylation products without the formation of regioisomers. Next, the
      control of enantioselectivity was studied. In the case of substrates 1 and 3, the
      reaction proceeded with good enantioselectivities by employing a chiral Lewis
      acid, prepared from chiral box ligand 24 and Zn(OTf)(2). For direct comparison,
      we also studied the reaction with other carbon radicals, derived from
      ICH(2)CO(2)Et, ICH(2)CN, BrC(CO(2)Et)(2)Me, and CCl(3)Br, which have
      electrophilic character.

PMID- 22963516
TI  - Characterization of lipids and lignans in brewer's spent grain and its
      enzymatically extracted fraction.
AB  - Brewer's spent grain (BSG), the major side stream of brewing, consists of the
      husks and the residual parts of malts after the mashing process. BSG was
      enzymatically fractionated by a two-step treatment with carbohydrate- and protein
      degrading enzymes, which solubilized 66% of BSG. BSG contained 11% lipids, which
      were mostly triglycerides, but also a notable amount of free fatty acids was
      present. Lipids were mostly solubilized due to the alkaline pH applied in the
      protease treatment. The main fatty acids were linoleic, palmitic, and oleic
      acids. Several lignans were identified in BSG, syringaresinol and
      secoisolariciresinol being the most abundant, many associated with the cell wall
      matrix and released by the alkaline-protease treatment.

PMID- 22963517
TI  - Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an
      automated method.
AB  - BACKGROUND: Disturbances in the myocardial extracellular volume fraction (ECV),
      such as diffuse or focal myocardial fibrosis or edema, are hallmarks of heart
      disease. Diffuse ECV changes are difficult to assess or quantify with
      cardiovascular magnetic resonance (CMR) using conventional late gadolinium
      enhancement (LGE), or pre- or post-contrast T1-mapping alone. ECV measurement
      circumvents factors that confound T1-weighted images or T1-maps, and has been
      shown to correlate well with diffuse myocardial fibrosis. The goal of this study
      was to develop and evaluate an automated method for producing a pixel-wise map of
      ECV that would be adequately robust for clinical work flow. METHODS: ECV maps
      were automatically generated from T1-maps acquired pre- and post-contrast
      calibrated by blood hematocrit. The algorithm incorporates correction of
      respiratory motion that occurs due to insufficient breath-holding and due to
      misregistration between breath-holds, as well as automated identification of the
      blood pool. Images were visually scored on a 5-point scale from non-diagnostic
      (1) to excellent (5). RESULTS: The quality score of ECV maps was 4.23 +/- 0.83 (m
      +/- SD), scored for n=600 maps from 338 patients with 83% either excellent or
      good. Co-registration of the pre-and post-contrast images improved the image
      quality for ECV maps in 81% of the cases. ECV of normal myocardium was 25.4 +/-
      2.5% (m +/- SD) using motion correction and co-registration values and was 31.5
      +/- 8.7% without motion correction and co-registration. CONCLUSIONS: Fully
      automated motion correction and co-registration of breath-holds significantly
      improve the quality of ECV maps, thus making the generation of ECV-maps feasible
      for clinical work flow.

PMID- 22963519
TI  - Out of mind, out of heart: attention affects duration of emotional experience.
AB  - It has been suggested that the extent to which a person maintains attention to
      pleasant versus unpleasant aspects of a given stimulus has an effect on the self
      reported affective state. This assumption was empirically tested in two
      experiments. In Study 1, participants received the instruction either to focus on
      a positive emotion-eliciting event (winning a tournament chess game) or to focus
      their attention on an affectively neutral distraction task (describing drawings).
      Study 2 used negative performance feedback in a cognitive task to induce
      unpleasant affect and included three experimental groups (waiting condition,
      continuing with the same cognitive task, distraction by a different cognitive
      task). Results converged to show that distracting attention away from the emotion
      eliciting event leads to a shorter duration of the emotional experience. These
      findings support the attention-focus hypothesis.

PMID- 22963518
TI  - Situating HIV risk in the lives of formerly trafficked female sex workers on the
      Mexico-US border.
AB  - Due to stigma and the psychosocial repercussions of past trauma and abuse,
      survivors of sex trafficking may experience increased susceptibility to violence,
      revictimization, and various harmful health outcomes, including HIV infection.
      Given the paucity of research characterizing the experiences of formerly
      trafficked female sex workers (FSWs), we set out to describe and contextualize
      perceptions of HIV risk among women who have experienced past episodes of sex
      trafficking and who are currently engaged in sex work in Tijuana, Mexico. Based
      on semi-structured interviews and ethnographic fieldwork, we describe the
      following interrelated themes as influencing formerly trafficked FSWs'
      perceptions and experiences of HIV risk: economic vulnerability; susceptibility
      to violence; and psychological trauma. Our findings highlight the need for HIV
      prevention efforts to incorporate broader structural and social interventions
      aimed at reducing vulnerability to violence and human rights abuses among this
      population and improving their general economic, psychological, and social well
      being.

PMID- 22963520
TI  - High-efficiency photoelectrocatalytic hydrogen generation enabled by palladium
      quantum dots-sensitized TiO2 nanotube arrays.
AB  - TiO(2) nanotube arrays (TNTAs) sensitized by palladium quantum dots (Pd QDs)
      exhibit highly efficient photoelectrocatalytic hydrogen generation. Vertically
      oriented TNTAs were prepared by a three-step electrochemical anodization.
      Subsequently, Pd QDs with uniform size and narrow size distribution were formed
      on TiO(2) nanotubes by a modified hydrothermal reaction (i.e., yielding
      nanocomposites of Pd QDs deposited on TNTAs, Pd@TNTAs). By exploiting Pd@TNTA
      nanocomposites as both photoanode and cathode, a substantially increased photon
      to-current conversion efficiency of nearly 100% at lambda = 330 nm and a greatly
      promoted photocatalytic hydrogen production rate of 592 MUmol.h(-1).cm(-2) under
      320 mW.cm(-2) irradiation were achieved. The synergy between nanotubular
      structures of TiO(2) and uniformly dispersed Pd QDs on TiO(2) facilitated the
      charge transfer of photoinduced electrons from TiO(2) nanotubes to Pd QDs and the
      high activity of Pd QDs catalytic center, thereby leading to high-efficiency
      photoelectrocatalytic hydrogen generation.

PMID- 22963521
TI  - Successful treatment of syringotropic CD8+ mycosis fungoides accompanied by
      hypohidrosis with vorinostat and retinoids.
AB  - We describe a 34-year-old Japanese man with syringotropic CD8+ mycosis fungoides
      (MF) accompanied by hypohidrosis who was treated with vorinostat and retinoids.
      Interestingly, immunohistochemical staining for dermcidin revealed a decrease of
      sweat in the eccrine glands, and a sweat test by the iodine starch method proved
      hypohidrosis in the MF-affected areas. Six months after treatment with this
      combination therapy, the patient's advanced MF was under control. 

PMID- 22963522
TI  - Molecular phylogeny, laboratory rearing, and karyotype of the bombycid moth,
      Trilocha varians.
AB  - This study describes the molecular phylogeny, laboratory rearing, and karyotype
      of a bombycid moth, Trilocha varians (F. Walker) (Lepidoptera: Bombycidae), which
      feeds on leaves of Ficus spp. (Rosales: Moraceae). The larvae of this species
      were collected in Taipei city, Taiwan, and the Ryukyu Archipelago (Ishigaki and
      Okinawa Islands, Japan). Molecular phylogenetic analyses revealed that T. varians
      belongs to the subfamily Bombycinae, thus showing a close relationship to the
      domesticated silkworm Bombyx mori (L.), a lepidopteran model insect. A laboratory
      method was developed for rearing T. varians and the time required for development
      from the embryo to adult was determined. From oviposition to adult emergence, the
      developmental zero was 10.47  degrees C and total effective temperature was 531.2
      day-degrees, i.e., approximately 30 days for one generation when reared at 28 
      degrees C. The haploid of T. varians consisted of n = 26 chromosomes. In highly
      polyploid somatic nuclei, females showed a large heterochromatin body, indicating
      that the sex chromosome system in T. varians is WZ/ZZ (female/male). The results
      of the present study should facilitate the utilization of T. varians as a
      reference species for B. mori, thereby leading to a greater understanding of the
      ecology and evolution of bombycid moths.

PMID- 22963523
TI  - Spontaneous trigeminal allodynia in rats: a model of primary headache.
AB  - Animal models are essential for studying the pathophysiology of headache
      disorders and as a screening tool for new therapies. Most animal models modify a
      normal animal in an attempt to mimic migraine symptoms. They require manipulation
      to activate the trigeminal nerve or dural nociceptors. At best, they are models
      of secondary headache. No existing model can address the fundamental question:
      How is a primary headache spontaneously initiated? In the process of obtaining
      baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we
      discovered a rat with spontaneous episodic trigeminal allodynia (manifested by
      episodically changing periorbital pain threshold). Subsequent mating showed that
      the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to
      study the pathophysiology of primary recurrent headache disorders. To validate
      this as a model for migraine, we tested the effects of clinically proven acute
      and preventive migraine treatments on spontaneous changes in rat periorbital
      sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed
      the low periorbital pain thresholds. Thirty days of chronic valproic acid
      treatment prevented spontaneous changes in trigeminal allodynia. After
      discontinuation, the rats returned to their baseline of spontaneous episodic
      threshold changes. We also tested the effects of known chemical human migraine
      triggers. On days when the rats did not have allodynia and showed normal
      periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related
      peptide induced significant decreases in the periorbital pain threshold. This
      model can be used as a predictive model for drug development and for studies of
      putative biomarkers for headache diagnosis and treatment.

PMID- 22963524
TI  - Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused
      by leukotriene C4 in precision cut lung slices in the horse.
AB  - BACKGROUND: Glucocorticoids have been proven to be effective in the therapy of
      recurrent airway obstruction (RAO) in horses via systemic as well as local
      (inhalative) administration. Elective analysis of the effects of this drug on
      bronchoconstriction in viable lung tissue offers an insight into the mechanism of
      action of the inflammatory cascade occurring during RAO which is still unclear.
      The mechanism of action of steroids in treatment of RAO is thought to be induced
      through classical genomic pathways. We aimed at electively studying the effects
      of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung
      slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on
      inhibiting bronchoconstriction in the horse. The inhibiting effect was measured
      through instillation of a known mediator of inflammation and bronchoconstriction,
      leukotriene C4. For this, the accessory lobes of 13 horses subjected to
      euthanasia for reasons unrelated to the respiratory apparatus were used to obtain
      viable lung slices. RESULTS: After 30 minutes of PCLS incubation, beclomethasone
      showed to significantly inhibit the contraction of the bronchioles after
      instillation with leukotriene C4. The EC50 values of the two contraction curves
      (LTC4 with and without BDP) differed significantly from each other (p = 0.002).
      The possibility of a non-genomic rapid mechanism of action seems likely since
      transcriptional activities require a longer lag period. CONCLUSIONS: In human
      neuroendocrinology, high levels of glucocorticoids have been proven to function
      via a non-genomic mechanism of membrane receptors. The concentration of
      beclomethasone used on the lung slices in our study can be considered as high.
      This allows speculation about similar rapid non-genomic mechanisms of high-dosage
      inhaled glucocorticoids in the lower airways of horses. However, further
      assessment on a molecular basis is needed to confirm this.

PMID- 22963525
TI  - Health-related quality of life and symptoms in patients with experiences of
      health problems related to dental restorative materials.
AB  - OBJECTIVES: The question of health risks associated with dental materials,
      especially dental amalgam, has long been controversial and remains unresolved.
      For the past 10 years, people in Sweden with perceived adverse reactions to
      dental restorative materials have been entitled to apply to their local county
      council for subsidized replacement of restorative materials. The aim of the study
      was to investigate symptoms, perceived health changes over time and health
      related quality of life (HRQoL) in this population, comprising subjects with
      subjective health impairment, allegedly because of dental materials. A further
      aim was to compare their HRQoL with that of the general population. METHODS: A
      comprehensive questionnaire was sent to 515 people who had applied for subsidized
      replacement of dental restorations. The questionnaire covered general and oral
      symptoms, HRQoL, health ratings over time and dental restoration replacement.
      RESULTS: The response rate was 54.4% (n=280). Most (83.2%) answered that they had
      undergone replacement of restorative materials because of impaired health,
      perceived to be related to dental restorative materials. The most common symptoms
      were musculoskeletal pain (67.5%), sleep disturbance (60.0%) and fatigue (58.6%).
      The HRQoL of the study subjects was significantly lower than that of the Swedish
      population in general. CONCLUSIONS: Subjects who had undergone subsidized dental
      restoration replacement reported persistent subjective symptoms and low HRQoL.
      The results indicate that replacement of restorative materials alone is
      insufficient to achieve improved health in patients with symptoms allegedly
      attributable to dental restorations.

PMID- 22963526
TI  - Effects of (un)employment on young couples' health and life satisfaction.
AB  - This study investigated effects of employed and unemployed job status on health
      outcomes with questionnaires in 50 young couples. Analysis of variance revealed
      higher pessimism, higher stress levels, and lower life satisfaction in couples in
      which one partner was unemployed. These couples also exhibited more health risk
      behaviours compared to couples in which both partners were working. The dyadic
      analysis of data, using an actor-partner interdependence model, demonstrated
      strong actor and partner effects for male partner's job status. Being unemployed
      was significantly associated not only with male partner's life satisfaction but
      also with the life satisfaction of his female partner. In addition, male
      partner's pessimism was identified as a significant variable which mediates
      between male partner's job status and female partner's life satisfaction. The
      study highlights the relevance of the accomplishment of tasks in the domains of
      work and partnership during young adulthood and it emphasises the gender specific
      importance.

PMID- 22963527
TI  - A retrospective study of Human Immunodeficiency Virus transmission, mortality and
      loss to follow-up among infants in the first 18 months of life in a prevention of
      mother-to-child transmission programme in an urban hospital in KwaZulu-Natal,
      South Africa.
AB  - BACKGROUND: Follow up of Human Immunodeficiency Virus (HIV)-exposed infants is
      an important component of Prevention of Mother-to-Child Transmission (PMTCT)
      programmes in order to ascertain infant outcomes post delivery. We determined HIV
      transmission, mortality and loss to follow-up (LTFU) of HIV-exposed infants
      attending a postnatal clinic in an urban hospital in Durban, South Africa.
      METHODS: We conducted a retrospective cohort study of infants born to women in
      the PMTCT programme at McCord Hospital, where mothers paid a fee for service.
      Data were abstracted from patient records for live-born infants delivered between
      1 May 2008 and 31 May 2009. The infants' LTFU status and age was based on the
      date of the last visit. HIV transmission was calculated as a proportion of
      infants followed and tested at six weeks. Mortality rates were analyzed using
      Kaplan-Meier (K-M), with censoring on 15 January 2010, LTFU or death. RESULTS: Of
      260 infants, 155 (59.6%) remained in care at McCord beyond 28 weeks: one died at
      < 28 days, three died between one to six months; 34 were LTFU within seven days,
      60 were LTFU by six months. K-M mortality rate: 1.7% at six months (95%
      confidence interval (CI): 0.6% to 4.3%). Of 220 (83%) infants tested for HIV at
      six weeks, six (2.7%, 95% CI: 1.1% to 5.8%) were HIV-infected. In Cox regression
      analysis, late antenatal attendance (>= 28 weeks gestation) relative to attending
      in the first trimester was a predictor for infant LTFU (adjusted hazards ratio =
      2.3; 95% CI: 1.0 to 5.1; p = 0.044). CONCLUSION: This urban PMTCT programme
      achieved low transmission rates at six weeks, but LTFU in the first six months
      limited our ability to examine HIV transmission up to 18 months and determinants
      of mortality. The LTFU of infants born to women who attended antenatal care at 28
      weeks gestation or later emphasizes the need to identify late antenatal attendees
      for follow up care to educate and support them regarding the importance of follow
      up care for themselves and their infants.

PMID- 22963528
TI  - Cardiovascular disease event rates in patients with severe psoriasis treated with
      systemic anti-inflammatory drugs: a Danish real-world cohort study.
AB  - OBJECTIVES: Psoriasis is a chronic inflammatory disorder associated with
      cardiovascular morbidity and mortality. Systemic anti-inflammatory drugs,
      including biological agents, are widely used in the treatment of patients with
      moderate to severe psoriasis and may attenuate the risk of cardiovascular disease
      events. We therefore examined the rate of cardiovascular disease events in
      patients with severe psoriasis treated with systemic anti-inflammatory drugs.
      DESIGN, SETTING AND PARTICIPANTS: Individual-level linkage of nationwide
      administrative databases was used to assess the event rates associated with use
      of biological agents, methotrexate or other therapies, including retinoids,
      cyclosporine and phototherapy, in Denmark from 2007 to 2009. MAIN OUTCOME
      MEASURE: Death, myocardial infarction and stroke. RESULTS: A total of 2400
      patients with severe psoriasis, including 693 patients treated with biological
      agents and 799 treated with methotrexate, were identified. Incidence rates per
      1000 patient-years and 95% confidence intervals (CIs) for the composite endpoint
      were 6.0 (95% CI 2.7-13.4), 17.3 (95% CI 12.3-24.3) and 44.5 (95% CI 34.6-57.0)
      for patients treated with biological agents, methotrexate and other therapies,
      respectively. Age- and sex-adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12
      0.64) and 0.65 (95% CI 0.42-1.00) for patients treated with biological agents and
      methotrexate, respectively, using other therapies as the reference cohort.
      Corresponding HRs for a secondary composite endpoint of cardiovascular death,
      myocardial infarction and stroke were 0.48 (95% CI 0.17-1.38) and 0.50 (95% CI
      0.26-0.97). CONCLUSION: In this nationwide study of patients with severe
      psoriasis, systemic anti-inflammatory treatment with biological agents or
      methotrexate was associated with lower cardiovascular disease event rates
      compared to patients treated with other anti-psoriatic therapies.

PMID- 22963529
TI  - P2Y12 inhibitors: pharmacologic mechanism and clinical relevance.
AB  - Platelets play a critical role in the pathogenesis of atherothrombotic processes
      and inhibition of platelet aggregation by antiplatelet therapy is essential and
      really important in the acute coronary syndromes or in the setting of
      percutaneous coronary intervention. The first family of adenosine diphosphate
      P2Y12 receptors inhibiting drug is represented by thienopyridines and among these
      ticlopidine was the first approved by Food and Drug Administration; actually its
      use is discouraged because of its potential side effects (neutropenia, anemia,
      gastrointestinal distress and thrombotic thrombocytopenic purpura). The second
      generation of thienopyridines is represented by clopidogrel that has replaced
      ticlopidine in the clinical practice; clopidogrel has the largest clinical
      experience. Prasugrel represents the third generation. It inhibits platelet
      aggregation by irreversibly blocking the adenosine diphosphate P2Y12 receptor.
      Ticagrelor, Cangrelor and Enilogrel represent the last generation of
      thienopyridines. This review is focused on the effects of adenosine diphosphate
      P2Y12 inhibitors.

PMID- 22963531
TI  - Global sensitivity analysis of the regional atmospheric chemical mechanism: an
      application of random sampling-high dimensional model representation to urban
      oxidation chemistry.
AB  - Chemical mechanisms play a crucial part for the air quality modeling and
      pollution control decision-making. Parameters in a chemical mechanism have
      uncertainties, leading to the uncertainties of model predictions. A recently
      developed global sensitivity analysis (SA) method based on Random Sampling-High
      Dimensional Model Representation (RS-HDMR) was applied to the Regional
      Atmospheric Chemical Mechanism (RACM) within a zero-dimensional photochemical
      model to highlight the main uncertainty sources of atmospheric hydroxyl (OH) and
      hydroperoxyl (HO(2)) radicals. This global SA approach can be applied as a
      routine in zero-dimensional photochemical modeling to comprehensively assess
      model uncertainty and sensitivity under different conditions. It also highlights
      the parameters to which the model is most sensitive during periods when the
      model/measurement OH and HO(2) discrepancies are greatest. Uncertainties in 584
      model parameters were assigned for measured constituents used to constrain the
      model, for photolysis and kinetic rate coefficients, and for product yields of
      the reactions. With simulations performed for the hourly field data of two
      typical days, modeled and measured OH and HO(2) generally agree better for
      polluted conditions than for cleaner conditions, except during morning rush hour.
      Sensitivity analysis shows that the modeled OH and HO(2) depend most critically
      on the reactions of xylenes and isoprene with OH, NO(2) with OH, NO with HO(2),
      and internal alkenes with O(3) and suggests that model/measurement discrepancies
      in OH and HO(2) would benefit from a closer examination of these reactions.

PMID- 22963530
TI  - Overexpression of membrane proteins in mammalian cells for structural studies.
AB  - The number of structures of integral membrane proteins from higher eukaryotes is
      steadily increasing due to a number of innovative protein engineering and
      crystallization strategies devised over the last few years. However, it is
      sobering to reflect that these structures represent only a tiny proportion of the
      total number of membrane proteins encoded by a mammalian genome. In addition, the
      structures determined to date are of the most tractable membrane proteins, i.e.,
      those that are expressed functionally and to high levels in yeast or in insect
      cells using the baculovirus expression system. However, some membrane proteins
      that are expressed inefficiently in these systems can be produced at sufficiently
      high levels in mammalian cells to allow structure determination. Mammalian
      expression systems are an under-used resource in structural biology and represent
      an effective way to produce fully functional membrane proteins for structural
      studies. This review will discuss examples of vertebrate membrane protein
      overexpression in mammalian cells using a variety of viral, constitutive or
      inducible expression systems.

PMID- 22963532
TI  - Risk factors for perioperative complications of laparoscopic adrenalectomy
      including single-site surgery.
AB  - PURPOSE: To determine predictive factors for perioperative complications of
      laparoscopic adrenalectomy (LA) including single-site surgery performed or
      supervised by experienced laparoscopic surgeons. PATIENTS AND METHODS: We
      retrospectively reviewed 265 consecutive unilateral LAs performed at a single
      institution from 2001 to 2011. All surgical procedures were performed or
      supervised by one of two experienced laparoscopic surgeons. The transabdominal
      approach was used in 248 patients, while a retroperitoneal approach was used in
      17 patients. Laparoendoscopic single-site adrenalectomy was performed in 58
      patients. Predictive factors for postoperative complications were analyzed.
      RESULTS: There were no postoperative deaths. At least one postoperative
      complication occurred in 12 (4.6%) patients. No patient underwent reoperation for
      a complication. Only one (0.4%) patient's procedure was converted to open
      surgery, and only this patient needed a blood transfusion during the operation.
      One patient who underwent laparoendoscopic single-site adrenalectomy had the
      procedure converted to conventional laparoscopic adrenalectomy. Multivariable
      logistic regression analysis showed that an American Society of Anesthesiologists
      physical status grade 3 or above was the only predictive factor for perioperative
      complications. CONCLUSION: American Society of Anesthesiologists-physical status
      grade 3 or above was a statistically significant factor for perioperative
      complications associated with laparoscopic adrenalectomy that involved
      laparoendoscopic single-site adrenalectomy, which was performed or supervised by
      an experienced laparoscopic surgeon. According to the findings of this
      retrospective study, single-site operation, obesity, adrenal tumor size, and
      tumor type may not be considered as risk factors for perioperative complications
      after LA performed or supervised by an experienced laparoscopic surgeon.

PMID- 22963534
TI  - Isolation of lomaiviticins C-E, transformation of lomaiviticin C to lomaiviticin
      A, complete structure elucidation of lomaiviticin A, and structure-activity
      analyses.
AB  - We describe the isolation of (-)-lomaiviticins C-E (6-8), elucidation of the
      complete absolute and relative stereochemistry of (-)-lomaiviticin A (1), the
      synthetic conversion of (-)-lomaiviticin C (6) to (-)-lomaiviticin A (1), and the
      first evidence that the dimeric diazofluorene of (-)-lomaiviticin A (1) plays a
      defining and critical role in antiproliferative activity.

PMID- 22963535
TI  - New insights into pharyngo-esophageal bolus transport revealed by pressure
      impedance measurement.
AB  - BACKGROUND: Pharyngeal propulsion, strength of peristalsis and esophago-gastric
      junction (EJG) resistance are determinants of esophageal bolus transport. This
      study used pressure-impedance methods to correlate pharyngo-esophageal function
      with the esophageal bolus trajectory pathway and pressures generated during bolus
      transport. METHODS: Pharyngo-esophageal pressure-impedance measurements were
      performed in 20 healthy adult controls. Pharyngeal automated impedance manometry
      (AIM) analysis was performed to derive pharyngeal swallow function variables. The
      esophageal time of nadir impedance (TZn) was used to track bolus trajectory
      pathway. The inflection, or flow stasis point (FSP), of the trajectory curve was
      determined as were the pressures within the bolus (PZn) above and below the FSP.
      The size of 20 mmHg isocontour defect (20 mmHg IC defect) measured the integrity
      of the peristaltic wave. KEY RESULTS: For viscous boluses, weaker pharyngeal
      bolus propulsion correlated with the FSP being located higher in the esophagus.
      Pressure within the bolus was observed to increase at the FSP and below the FSP
      in a manner that correlated with the magnitude of esophageal peak pressures.
      Larger 20 mmHg IC defects were associated with lower pressures within the bolus
      at the FSP and below. CONCLUSIONS & INFERENCES: The FSP of the bolus trajectory
      pathway appears to represent a switch from bolus propulsion due to pharyngeal
      mechanisms to bolus propulsion due to esophageal mechanisms. 20 mmHg IC defects
      significantly reduce bolus driving pressure at or below the FSP.

PMID- 22963536
TI  - The measurement and prevalence of an ideational model of family and economic
      development in Nepal.
AB  - Developmental idealism (DI) is a system of beliefs and values that endorses
      modern societies and families and sees them as occurring together, with modern
      families as causes and consequences of societal development. This study was
      motivated by the belief that the population of Nepal has absorbed these ideas and
      that the ideas affect their family behaviour. We use data collected in Nepal in
      2003 to show that Nepalis discuss ideas about development and its relationship to
      family life and that DI has been widely accepted. It is related in predictable
      ways to education, paid employment, rural-urban residence, and mass media
      exposure. Although it would be useful to know its influence on demographic
      decision-making and behaviour, we cannot evaluate this with our one-time cross
      sectional survey. Our data and theory suggest that this influence may be
      substantial.

PMID- 22963533
TI  - Mutation of the cytosolic ribosomal protein-encoding RPS10B gene affects shoot
      meristematic function in Arabidopsis.
AB  - BACKGROUND: Plant cytosolic ribosomal proteins are encoded by small gene
      families. Mutants affecting these genes are often viable, but show growth and
      developmental defects, suggesting incomplete functional redundancy within the
      families. Dormancy to growth transitions, such as the activation of axillary buds
      in the shoot, are characterised by co-ordinated upregulation of ribosomal protein
      genes. RESULTS: A recessive mutation in RPS10B, one of three Arabidopsis genes
      encoding the eukaryote-specific cytoplasmic ribosomal protein S10e, was found to
      suppress the excessive shoot branching mutant max2-1. rps10b-1 mildly affects the
      formation and separation of shoot lateral organs, including the shoot axillary
      meristems. Axillary meristem defects are enhanced when rps10b-1 is combined with
      mutations in REVOLUTA, AUXIN-RESISTANT1, PINOID or another suppressor of max2-1,
      FAR-RED ELONGATED HYPOCOTYL3. In some of these double mutants, the maintenance of
      the primary shoot meristem is also affected. In contrast, mutation of ALTERED
      MERISTEM PROGRAMME1 suppresses the rps10b-1axillary shoot defect. Defects in both
      axillary shoot formation and organ separation were enhanced by combining rps10b-1
      with cuc3, a mutation affecting one of three Arabidopsis NAC transcription factor
      genes with partially redundant roles in these processes. To assess the effect of
      rps10b-1 on bud activation independently from bud formation, axillary bud
      outgrowth on excised cauline nodes was analysed. The outgrowth rate of untreated
      buds was reduced only slightly by rps10b-1 in both wild-type and max2-1
      backgrounds. However, rps10b-1 strongly suppressed the auxin resistant outgrowth
      of max2-1 buds. A developmental phenotype of rps10b-1, reduced stamen number, was
      complemented by the cDNA of another family member, RPS10C, under the RPS10B
      promoter. CONCLUSIONS: RPS10B promotes shoot branching mainly by promoting
      axillary shoot development. It contributes to organ boundary formation and leaf
      polarity, and sustains max2-1 bud outgrowth in the presence of auxin. These
      processes require the auxin response machinery and precise spatial distribution
      of auxin. The correct dosage of protein(s) involved in auxin-mediated patterning
      may be RPS10B-dependent. Inability of other RPS10 gene family members to maintain
      fully S10e levels might cause the rps10b-1 phenotype, as we found no evidence for
      unique functional specialisation of either RPS10B promoter or RPS10B protein.

PMID- 22963537
TI  - Determination of the caffeine contents of various food items within the Austrian
      market and validation of a caffeine assessment tool (CAT).
AB  - The caffeine content of 124 products, including coffee, coffee-based beverages,
      energy drinks, tea, colas, yoghurt and chocolate, were determined using RP-HPLC
      with UV detection after solid-phase extraction. Highest concentrations of
      caffeine were found for coffee prepared from pads (755 mg l-1) and regular
      filtered coffee (659 mg l-1). The total caffeine content of coffee and chocolate
      based beverages was between 15 mg l-1 in chocolate milk and 448 mg l-1 in canned
      ice coffee. For energy drinks the caffeine content varied in a range from 266 to
      340 mg l-1. Caffeine concentrations in tea and ice teas were between 13 and 183
      mg l-1. Coffee-flavoured yoghurts ranged from 33 to 48 mg kg-1. The caffeine
      concentration in chocolate and chocolate bars was between 17 mg kg-1 in whole
      milk chocolate and 551 mg kg-1 in a chocolate with coffee filling. A caffeine
      assessment tool was developed and validated by a 3-day dietary record (r2= 0.817,
      p < 0.01) using these analytical data and caffeine saliva concentrations (r2=
      0.427, p < 0.01).

PMID- 22963538
TI  - Screening of selected ethnomedicinal plants from South Africa for larvicidal
      activity against the mosquito Anopheles arabiensis.
AB  - BACKGROUND: This study was initiated to establish whether any South African
      ethnomedicinal plants (indigenous or exotic), that have been reported to be used
      traditionally to repel or kill mosquitoes, exhibit effective mosquito larvicidal
      properties. METHODS: Extracts of a selection of plant taxa sourced in South
      Africa were tested for larvicidal properties in an applicable assay. Thirty 3rd
      instar Anopheles arabiensis larvae were exposed to various extract types
      (dichloromethane, dichloromethane/methanol) (1:1), methanol and purified water)
      of each species investigated. Mortality was evaluated relative to the positive
      control Temephos (Mostop; Agrivo), an effective emulsifiable concentrate
      larvicide. RESULTS: Preliminary screening of crude extracts revealed substantial
      variation in toxicity with 24 of the 381 samples displaying 100% larval mortality
      within the seven day exposure period. Four of the high activity plants were
      selected and subjected to bioassay guided fractionation. The results of the
      testing of the fractions generated identified one fraction of the plant, Toddalia
      asiatica as being very potent against the An. arabiensis larvae. CONCLUSION: The
      present study has successfully identified a plant with superior larvicidal
      activity at both the crude and semi pure fractions generated through bio-assay
      guided fractionation. These results have initiated further research into
      isolating the active compound and developing a malaria vector control tool.

PMID- 22963539
TI  - Membrane dynamics and interactions in measles virus dendritic cell infections.
AB  - Viral entry, compartmentalization and transmission depend on the formation of
      membrane lipid/protein microdomains concentrating receptors and signalosomes.
      Dendritic cells (DCs) are prime targets for measles virus (MV) infection, and
      this interaction promotes immune activation and generalized immunosuppression,
      yet also MV transport to secondary lymphatics where transmission to T cells
      occurs. In addition to MV trapping, DC-SIGN interaction can enhance MV uptake by
      activating cellular sphingomyelinases and, thereby, vertical surface transport of
      its entry receptor CD150. To exploit DCs as Trojan horses for transport, MV
      promotes DC maturation accompanied by mobilization, and restrictions of viral
      replication in these cells may support this process. MV-infected DCs are unable
      to support formation of functional immune synapses with conjugating T cells and
      signalling via viral glycoproteins or repulsive ligands (such as semaphorins)
      plays a key role in the induction of T-cell paralysis. In the absence of antigen
      recognition, MV transmission from infected DCs to T cells most likely involves
      formation of polyconjugates which concentrate viral structural proteins, viral
      receptors and with components enhancing either viral uptake or conjugate
      stability. Because DCs barely support production of infectious MV particles,
      these organized interfaces are likely to represent virological synapses essential
      for MV transmission.

PMID- 22963540
TI  - Artificial forisomes are ideal models of forisome assembly and activity that
      allow the development of technical devices.
AB  - Forisomes are protein polymers found in leguminous plants that have the
      remarkable ability to undergo reversible "muscle-like" contractions in the
      presence of divalent cations and in extreme pH environments. To gain insight into
      the molecular basis of forisome structure and assembly, we used confocal laser
      scanning microscopy to monitor the assembly of fluorescence-labeled artificial
      forisomes in real time, revealing two distinct assembly processes involving
      either fiber elongation or fiber alignment. We also used scanning and
      transmission electron microscopy and X-ray diffraction to investigate the
      ultrastructure of forisomes, finding that individual fibers are arranged into
      compact fibril bundles that disentangle with minimal residual order in the
      presence of calcium ions. To demonstrate the potential applications of artificial
      forisomes, we created hybrid protein bodies from forisome subunits fused to the B
      domain of staphylococcal protein A. This allowed the functionalization of the
      artificial forisomes with antibodies that were then used to target forisomes to
      specific regions on a substrate, providing a straightforward approach to develop
      forisome-based technical devices with precise configurations. The functional
      contractile properties of forisomes are also better preserved when they are
      immobilized via affinity reagents rather than by direct contact to the substrate.
      Artificial forisomes produced in plants and yeast therefore provide an ideal
      model for the investigation of forisome structure and assembly and for the design
      and testing of tailored artificial forisomes for technical applications.

PMID- 22963541
TI  - Detection of novel LAMA3 mutation in Herlitz junctional epidermolysis bullosa in
      a Jordanian family.
AB  - The Herlitz junctional epidermolysis bullosa (H-JEB) subtype usually presents as
      a severe lethal inherited variant of epidermolysis bullosa (EB) caused by a
      homozygous mutation in the genes LAMA3, LMAB3, or LAMAC3. Each gene encodes one
      of the three chains of heterotrimer laminin-332 proteins (including the alpha-3
      chain, beta-3 chain and gamma-2-chain) responsible for the adherence of the
      epidermis to the underlying dermis. The aim of this report is to add to the
      existing knowledge about EB by describing a novel mutation in a gene responsible
      for genodermatosis. A case of a Jordanian male neonate, born to healthy, first
      cousin consanguineous parents, who developed nonhealing blistering skin and
      mucous membrane lesions, crusted erosions with significant granulation tissue and
      dystrophic nails immediately after birth is described. The patient was diagnosed
      as having a novel LAMA3 mutation causing (H-JEB) by immunofluorescence mapping
      and molecular analysis. Both parents and this baby's sibling were shown to be
      heterozygous carriers of the same mutation. Pre-implantation diagnosis using
      molecular analysis for subsequent pregnancies in this family is crucial for
      managing any new pregnancy. 

PMID- 22963542
TI  - Pressurized liquid extraction of diesel and air particulate standard reference
      materials: effect of extraction temperature and pressure.
AB  - Four particulate matter Standard Reference Materials (SRMs) available from the
      National Institute of Standards and Technology (NIST) were used to evaluate the
      effect of solvent, number of static cycles and static times, pressure, and
      temperature when using pressurized liquid extraction (PLE) for the extraction of
      polycyclic aromatic hydrocarbons (PAHs) and nitrated-PAHs. The four materials
      used in the study were SRM 1648a Urban Particulate Matter, SRM 1649b Urban Dust,
      SRM 1650b Diesel Particulate Matter, and SRM 2975 Diesel Particulate Matter
      (Industrial Forklift). The results from the study indicate that the choice of
      solvent, dichloromethane compared to toluene and toluene/methanol mixtures, had
      little effect on the extraction efficiency. With three to five extraction cycles,
      increasing the extraction time for each cycle from 5 to 30 min had no significant
      effect on the extraction efficiency. The differences in extraction efficiency
      were not significant (with over 95% of the differences being <10%) when the
      pressure was increased from 13.8 to 20.7 MPa. The largest increase in extraction
      efficiency occurred for selected PAHs when the temperature of extraction was
      increased from 100 to 200  degrees C. At 200  degrees C naphthalene, biphenyl,
      fluorene, dibenzothiophene, and anthracene show substantially higher mass
      fractions (>30%) than when extracted at 100  degrees C in all the SRMs studied.
      For SRM 2975, large increases (>100%) are also observed for some other PAHs
      including benz[a]anthracene, benzo[k]fluoranthene, benzo[e]pyrene,
      benzo[a]pyrene, benzo[ghi]perylene, and benzo[b]chrysene when extracted at the
      higher temperatures; however, similar trends were not observed for the other
      diesel particulate sample, SRM 1650b. The results are discussed in relation to
      the use of the SRMs for evaluating analytical methods.

PMID- 22963543
TI  - 'The letting go, the building up, [and] the gradual process of rebuilding':
      identity change and post-traumatic growth in myalgic encephalomyelitis/chronic
      fatigue syndrome.
AB  - The aim of this study was to explore the phenomenon of identity change and
      subsequent post-traumatic growth (PTG) in individuals with myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS). Ten participants (average
      illness duration 7.4 years) were interviewed (average length, 79 minutes) via a
      semi-structured interview schedule and verbatim transcriptions were analysed with
      interpretative phenomenological analysis. The four superordinate themes revealed
      were 'comparisons of past to present self: "you have to be someone else, and you
      have to live with that''', 'the effect of social isolation on identity and
      subsequent insights into others' behaviours', 'contemplation of future and
      identity: ''where do I go from here?"', and 'PTG: "the letting go, the building
      up, [and] the gradual process of rebuilding"'. These themes outlined the
      experiences of those with ME/CFS as they underwent changes in identity due to the
      limitations the condition imposed on activities and roles, understanding others'
      behaviours after a period of isolation, the comparison of the past self with the
      present self and finally, the positive growth that was noted by two of the
      interviewees with regards to a new 'true' self. Despite the distressing and
      unpredictable nature of ME/CFS, it appears that individuals with this disorder
      can experience personal growth.

PMID- 22963544
TI  - Morphometric and genetic differentiation of two sibling gossamer-wing
      damselflies, Euphaea formosa and E. yayeyamana, and adaptive trait divergence in
      subtropical East Asian islands.
AB  - Insular species frequently demonstrate different tendencies to become smaller or
      larger than their continental relatives. Two sibling gossamer-wing damselflies,
      Euphaea formosa (Odonata: Euphaeidae) from Taiwan and E. yayeyamana from the
      Yaeyama Islands of Japan, have no clear structural differentiation, and can only
      be recognized by their geographical distribution, sizes, and subtle differences
      in wing shape and coloration. This study combined morphometric and genetic
      techniques to investigate the adaptive significance of trait divergence and
      species status in these two Euphaea damselflies. Phylogenetic analyses of the
      mitochondrial cox2 sequences demonstrated that the two damselflies are
      monophyletic lineages and constitute valid phylogenetic species. The landmark
      based geometric morphometrics indicated that the two damselflies are different
      morphological species characterized by distinctive wing shapes. The larger E.
      formosa exhibited broader hind wings, whereas E. yayeyamana had narrower and
      elongated forewings. The body size and wing shape variations among populations of
      the two species do not follow the expected pattern of neutral evolution,
      suggesting that the evolutionary divergence of these two traits is likely to be
      subjected to natural or sexual selection. The decreased body size, elongated
      forewings, and narrower hind wings of E. yayeyamana may represent insular
      adaptation to limited resources and reduced territorial competition on smaller
      islands.

PMID- 22963545
TI  - Nanomaterials in plant protection and fertilization: current state, foreseen
      applications, and research priorities.
AB  - Scientific publications and patents on nanomaterials (NM) used in plant
      protection or fertilizer products have exponentially increased since the
      millennium shift. While the United States and Germany have published the highest
      number of patents, Asian countries released most scientific articles. About 40%
      of all contributions deal with carbon-based NM, followed by titanium dioxide,
      silver, silica, and alumina. Nanomaterials come in many diverse forms
      (surprisingly often ?100 nm), from solid doped particles to (often nonpersistent)
      polymer and oil-water based structures. Nanomaterials serve equally as additives
      (mostly for controlled release) and active constituents. Product efficiencies
      possibly increased by NM should be balanced against enhanced environmental NM
      input fluxes. The dynamic development in research and its considerable public
      perception are in contrast with the currently still very small number of NM
      containing products on the market. Nanorisk assessment and legislation are
      largely in their infancies.

PMID- 22963546
TI  - Perceptions of neighborhood social environment and drug dependence among
      incarcerated women and men: a cross-sectional analysis.
AB  - BACKGROUND: Perception of neighborhood social environment can influence an
      individual's susceptibility to drug dependence. However, this has never been
      examined with a jailed sample, where frequent transitions between local jails and
      disadvantaged neighborhoods are common. Understanding these associations could
      aid in the design of targeted programs to decrease drug dependence and recidivism
      among the incarcerated. METHODS: For this study, 596 women and men from three
      Kansas City jails were surveyed over the course of six months in 2010. Drug
      dependence was assessed with DSM-IV criteria. Independent variables included fear
      of one's neighborhood, perceived level of neighborhood violence, and social
      capital. All data were self-reported and were analyzed using logistic regression.
      RESULTS: Controlling for gender and age, fear of neighborhood violence was
      associated with increased odds of having drug dependence (OR = 1.27, CI 1.02,
      1.58) and a higher level of social capital prior to incarceration was associated
      with lower odds of drug dependence (OR = 0.65, CI 0.44, 0.96). Mental health
      problem diagnosis and past year intimate partner violence were significant
      mediating factors. Gender and race/ethnicity were significant moderating factors
      between neighborhood disadvantage and drug dependence. CONCLUSIONS: Our study
      suggests that drug dependence programs for women and men who cycle between jails
      and communities require both individual- and community-level interventions. To be
      most effective, programs at the community-level should focus on helping specific
      groups navigate their communities, as well as address individual health needs
      associated with drug dependence.

PMID- 22963547
TI  - Improvement in headaches with continuous positive airway pressure for obstructive
      sleep apnea: a retrospective analysis.
AB  - OBJECTIVE: We aimed to identify clinical features in patients with severe
      headaches that predicted obstructive sleep apnea (OSA) and determine clinical and
      sleep study characteristics that predicted headache improvement with continuous
      positive airway pressure (CPAP). BACKGROUND: Many patients with headaches
      complain of sleep symptoms and have OSA. There is often improvement of headaches
      with CPAP treatment. METHODS: We conducted a retrospective chart review of all
      patients referred to adult neurology clinic for headaches and sent for
      polysomnography between January 2008 and December 2009. Follow-up ranged from 18
      to 42 months. RESULTS: Eighty-two headache patients (70 females, 12 males) were
      studied. Mean age was 45+/-13 years (females 45+/-13, males 43+/-11) and mean
      body mass index was 32+/-9. Headache types included 17% chronic migraine without
      aura, 22% episodic migraine without aura, 32% migraine with aura, 21% tension
      type headache, 6% chronic post-traumatic headache, 11% medication overuse
      headache, and 7% other types. All patients were receiving standard treatment for
      their headaches by their neurologist. Fifty-two patients (63%) had OSA.
      Increasing age, female gender, and chronic migraine without aura were predictive
      of OSA. Of the patients with OSA, 33 (63%) used CPAP and 27 (82%) were adherent
      to CPAP. Headache improvement was reported by 40 patients (49%) due to either
      standard medical therapy or CPAP. Patients with OSA who were CPAP adherent
      (21/27) were more likely to have improvement in headaches than patients
      intolerant of CPAP (2/6), those that did not try CPAP (8/19), and those who did
      not have OSA (16/30) (P=.045). Of the 33 patients who used CPAP, 13 reported
      improvement in headaches specifically due to CPAP therapy and 10 additional
      patients noted benefit in sleep symptoms. The presence of witnessed apneas
      (P=.045) and male gender (P=.021) predicted improvement in headaches due to CPAP.
      CONCLUSIONS: Headache patients should be evaluated for the presence of OSA.
      Treating OSA improves headaches in some patients.

PMID- 22963548
TI  - Osmium-catalyzed vicinal oxyamination of alkenes by N-(4
      toluenesulfonyloxy)carbamates.
AB  - N-(4-toluenesulfonyloxy)carbamates based on a range of common amine protecting
      groups serve as preformed nitrogen sources in the intermolecular osmium-catalyzed
      oxyamination reaction of a variety of mono-, di-, and trisubstituted alkenes. The
      reactions occur with low catalyst loadings and good yields and afford high
      regioselectivity for unsymmetrically substituted alkenes.

PMID- 22963549
TI  - On the DMSO-dissolved state of insulin: a vibrational spectroscopic study of
      structural disorder.
AB  - Upon dissolving in dimethyl sulfoxide (DMSO), native insulin and insulin amyloid
      fibrils convert into an identical disordered structural state based on IR
      spectral characteristics. Here, we investigate the DMSO-denatured state of
      insulin using a number of spectroscopic methods: near-UV circular dichroism,
      infrared absorption spectroscopy, vibrational circular dichroism (VCD), Raman
      scattering, and Raman optical activity (ROA), as well as by carrying out 140-ns
      long molecular dynamics (MD) simulations of DMSO-dissolved native insulin
      monomers. According to this work, the DMSO-solvated state of insulin is an
      ensemble of conformations including polyproline II-type helix and possibly a
      residual alpha-helical structure. Effects of DMSO-specific solvation and
      conformation-restricting covalent structure of insulin (including the three
      intact disulfide bridges) are argued to play important roles in stabilizing the
      disordered state of the protein. A comparison of ROA spectra of insulin dissolved
      in fully deuterated and nondeuterated DMSO suggested transfer of chirality from
      the protein to the otherwise ROA-silent solvent. Our study provides an example of
      a biological protein that acquires a substantial population of PP II conformation
      in an entirely nonaqueous environment. The DMSO-unfolded state of insulin and its
      dynamics are also discussed in the context of the established link between PP II
      conformation and protein misfolding.

PMID- 22963550
TI  - Inequalities in mortality among refugees and immigrants compared to native Danes-
      a historical prospective cohort study.
AB  - BACKGROUND: Comparisons of mortality patterns between different migrant groups,
      and between migrants and natives, are relevant to understanding, and ultimately
      reducing, inequalities in health. To date, European studies on migrants'
      mortality patterns are scarce and are based solely on country of birth, rather
      than migrant status. However, mortality patterns may be affected by implications
      in relation to migrant status, such as health hazards related to life
      circumstances before and during migration, and factors related to ethnic origin.
      Consequently, we investigated differences in both all-cause and cause-specific
      mortality from cancer and cardiovascular disease among refugees and immigrants,
      compared with the mortality among native Danes. METHODS: A register-based,
      historical prospective cohort design. All refugees (n = 29,139) and family
      reunited immigrants (n = 27,134) who, between 1 January 1993 and 31 December
      1999, were granted right of residence in Denmark were included and matched 1:4 on
      age and sex with native Danes. To identify deaths, civil registration numbers
      were cross-linked to the Register of Causes of Death (01.01.1994-31.12.2007) and
      the Danish Civil Registration System (01.01.1994-31.12.2008). Mortality rate
      ratios were estimated separately for men and women by migrant status and region
      of birth, adjusting for age and income and using a Cox regression model, after a
      median follow-up of 10-13 years after arrival. RESULTS: Compared with native
      Danes, all-cause mortality was significantly lower among female (RR = 0.78;
      95%CI: 0.71;0.85) and male (RR = 0.64; 95%CI: 0.59-0.69;) refugees. The rates
      were also significantly lower for immigrants: women (RR = 0.44; 95%CI: 0.38;0.51)
      and men (RR = 0.43; 95%CI: 0.37;0.51). Both migrant groups also had lower cause
      specific mortality from cancer and cardiovascular diseases. For both all-cause
      and cause-specific mortality, immigrants generally had lower mortality than
      refugees, and differences were observed according to ethnic origin. CONCLUSIONS:
      Mortality patterns were overall advantageous for refugees and immigrants compared
      with native Danes. Research should concentrate on disentangling the reasons
      behind migrants' health advantages, in order to enlighten future preventive
      public-health efforts, for the benefit of the entire population.

PMID- 22963551
TI  - Enhanced giant magnetoimpedance in heterogeneous nanobrush.
AB  - A highly sensitive and large working range giant magnetoimpedance (GMI) effect
      is found in the novel nanostructure: nanobrush. The nanostructure is composed of
      a soft magnetic nanofilm and a nanowire array, respectively fabricated by RF
      magnetron sputtering and electrochemical deposition. The optimal GMI ratio of
      nanobrush is promoted to more than 250%, higher than the pure FeNi film and some
      sandwich structures at low frequency. The design of this structure is based on
      the vortex distribution of magnetic moments in thin film, and it can be induced
      by the exchange coupling effect between the interfaces of nanobrush.

PMID- 22963552
TI  - Pharmacological and dietary antioxidant therapies for chronic obstructive
      pulmonary disease.
AB  - The progression and exacerbations of chronic obstructive pulmonary disease (COPD)
      are intimately associated with tobacco smoke/biomass fuel-induced oxidative and
      aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases
      and transcription factors, steroid resistance, unfolded protein response, mucus
      hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic
      changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and
      skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In
      light of the above it would be prudent to target systemic and local oxidative
      stress with agents that can modulate the antioxidants/ redox system or by
      boosting the endogenous levels of antioxidants for the treatment and management
      of COPD. Identification of various antioxidant agents, such as thiol molecules
      (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine, N-acystelyn,
      erdosteine, fudosteine, ergothioneine, and carbocysteine lysine salt), dietary
      natural product-derived polyphenols and other compounds (curcumin, resveratrol,
      green tea catechins, quercetin sulforaphane, lycopene, acai, alpha-lipoic acid,
      tocotrienols, and apocynin) have made it possible to modulate various biochemical
      aspects of COPD. Various researches and clinical trials have revealed that these
      antioxidants can detoxify free radicals and oxidants, control expression of redox
      and glutathione biosynthesis genes, chromatin remodeling, and ultimately
      inflammatory gene expression. In addition, modulation of cigarette smoke-induced
      oxidative stress and related cellular changes have also been reported to be
      effected by synthetic molecules. This includes specific spin traps like alpha
      phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins
      (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, lipid
      peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and
      lazaroids/tirilazad, myeloperoxidase inhibitors, as well as specialized pro
      resolving mediators/inflammatory resolving lipid mediators, omega-3 fatty acids,
      vitamin D, and hydrogen sulfide. According to various studies it appears that the
      administration of multiple antioxidants could be a more effective mode used in
      the treatment of COPD. In this review, various pharmacological and dietary
      approaches to enhance lung antioxidant levels and beneficial effects of
      antioxidant therapeutics in treating or intervening the progression of COPD have
      been discussed.

PMID- 22963553
TI  - Inhaled muscarinic acetylcholine receptor antagonists for treatment of COPD.
AB  - Bronchodilators, generally administered via metered dose or dry powder inhalers,
      are the mainstays of pharmacological treatment of stable COPD. Inhaled long
      acting beta-agonists (LABA) and anticholinergics are the bronchodilators
      primarily used in the chronic treatment of COPD. Anticholinergics act as
      muscarinic acetylcholine receptor antagonists and are frequently preferred over
      beta-agonists for their minimal cardiac stimulatory effects and greater efficacy
      in most studies. Their therapeutic efficacy is based on the fact that vagally
      mediated bronchoconstriction is the major reversible component of airflow
      obstruction in patients with COPD. However, bronchodilators are effective only on
      the reversible component of airflow obstruction, which by definition is limited,
      as COPD is characterized by a fixed or poorly reversible airflow obstruction.
      Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD
      include ipratropium bromide, oxitropium bromide and tiotropium bromide.
      Ipratropium bromide, the prototype of anticholinergic bronchodilators, is a short
      acting agent. Oxitropium bromide is administered twice a day. Tiotropium bromide,
      the only long-acting antimuscarinic agent (LAMA) currently approved, is
      administered once a day. Newer LAMAs including aclidinium bromide and
      glycopyrrolate bromide are currently in phase III development for treatment of
      COPD. Some new LAMAs, including glycocpyrrolate, are suitable for once daily
      administration and, unlike tiotropium, have a rapid onset of action. New LAMAs
      and their combination with ultra-LABA and, possibly, inhaled corticosteroids,
      seem to open new perspectives in the management of COPD. Dual-pharmacology
      muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to
      the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a
      single molecule.

PMID- 22963554
TI  - Development of new drugs for COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is an increasing global health
      problem and cause of death. COPD is a chronic inflammatory disease predominantly
      affecting small airways and lung parenchyma that leads to progressive airway
      obstruction. However, current therapies fail to prevent either disease
      progression or mortality. The mainstay of current drug therapy is long-acting
      bronchodilators. Several once daily inhaled beta(2)-agonists and muscarinic
      antagonists (and combinations) are now in development. No treatments effectively
      suppress chronic inflammation in COPD lungs. With better understanding of the
      inflammatory and destructive process in the pathophysiology of COPD, several new
      therapeutic targets have been identified. Several mediator antagonists or
      inhibitors tested in COPD have so far been disappointing, but CXCR2 antagonists
      that block pulmonary neutrophil and monocyte recruitment are more promising.
      Broad spectrum anti-inflammatory drugs may be more effective, and include
      inhibitors of the proinflammatory enzymes phosphodiesterase-4, p38 mitogen
      activated protein kinase, Janus kinases, NF-kappaB kinase and PI3 kinase-gamma
      and -delta, but side effects after oral administration are a major limitation so
      that in future inhaled delivery may be necessary. A new promising approach is
      reversal of corticosteroid resistance through increasing histone deacetylase-2
      (HDAC2) activity. This might be achieved by existing treatments such as
      theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase
      delta inhibitors. Thus although there have been major advances in the development
      of long-acting bronchodilators for COPD, it has proved difficult to find anti
      inflammatory treatments that are safe and effective.

PMID- 22963555
TI  - Antiretrovirals for HIV Exposure Prophylaxis.
AB  - Infection with Human Immunodeficiency Virus (HIV) remains a global public health
      problem. Although the epidemic has not been completely controlled, there was
      considerable progress in HIV prevention and treatment during the last 30 years.
      The modern prevention approaches are multi-component including also the
      administration of combinations of potent antiretroviral agents as a prophylaxis
      after occupational or non-occupational exposures to HIV. The aim of the current
      review is to present the chemical and pharmacological characteristics of
      antiretroviral drugs used in HIV prophylaxis and to describe briefly the medical
      management of exposures to potentially infectious body fluids.

PMID- 22963556
TI  - Antiviral drugs in the prophylaxis of HBV infection.
AB  - Reactivation of hepatitis B infection (HBV) is known to occur in liver graft
      recipients and in chronic carriers of the surface antigen of HBV who receive
      immunosuppressive therapy. The use of hepatitis B immune globulin alone or in
      combination with antiviral agents such as lamivudine, adefovir, tenofovir,
      entecavir, famciclovir, ganciclovir, as prophylaxis in HBV liver transplants, has
      been well documented. In terms of HBV positive carriers undergoing cytotoxic
      chemotherapy, the preemptive use of nucleoside or nucleotide analogues seems to
      be effective. Monotherapy or combination of antiviral drugs, as well as the
      optimal duration of HBV prophylaxis, is to be determined.

PMID- 22963557
TI  - Antivirals used for influenza chemoprophylaxis.
AB  - Current data about the role of adamantanes and neuraminidase inhibitors (NIs) in
      the chemoprophylaxis against influenza viruses were reviewed. We found
      significant evidence favouring the role of NIs in the chemoprophylaxis of
      influenza. Awareness and prudent use are necessary, due to recent evidence of
      gradually increasing resistance of several influenza strains to these agents. On
      the other hand, the role of adamantanes appears to have decreased over the last
      decade. Both pre-pandemic and the novel pandemic A/H1N1 2009 strains exhibited
      either increasing rates of resistance or no susceptibility to adamantanes.
      Adamantanes currently only have a theoretical role in influenza chemoprophylaxis
      given the likelihood of the occurrence of an epidemic due to a susceptible
      strain. In conclusion, changes in antiviral susceptibility will affect future
      guidance in prophylaxis against influenza. Further investigation of novel
      medications with new mechanisms of action is important in this regard. Meanwhile,
      implementing strategies to conserve our current antivirals is necessary.

PMID- 22963558
TI  - Cytomegalovirus prophylaxis in solid organ transplantation.
AB  - Human Cytomegalovirus is a commonly identified herpesvirus that establishes a
      state of latent infection in the majority of the population by adulthood. A
      coordinated immune response involving both the innate and adaptive immune system
      prevents active viral replication and disease. Cellular immunity appears
      particularly important to control of viremia requiring both a CMV-specific CD4+
      and CD8+ T cell response. Solid organ transplant recipients are particularly
      susceptible to CMV related disease due to the immunosuppression necessary to
      prevent organ rejection, with patients receiving T cell depleting therapies being
      at highest risk. The deleterious outcomes of CMV in organ transplant recipients
      result from both direct cytopathic and indirect immune-modulatory effects of CMV
      viral replication. The recognition of the negative effects of CMV in solid organ
      transplantation has resulted in the routine prophylaxis of organ recipients with
      antiviral nucleoside analogues. The appropriate duration of therapy is still
      controversial although guidelines do exist. The ability to assay an individual
      immune response to CMV should allow for tailored duration of therapy in the
      future.

PMID- 22963559
TI  - Editorial: prophylactic treatment with antiviral agents to prevent infection and
      disease.

PMID- 22963560
TI  - Interactions between calcium and cAMP signaling.
AB  - The calcium ion is quite possibly the single most pervasive signaling molecule
      used by living organisms for the purpose of communicating internal and external
      states. It differs from other messengers in that it is neither created nor
      destroyed, but just moved around inside and outside the cell via transporters,
      pumps and channels to alter its concentration in specific cellular locations.
      These changes in free [Ca(2+)] are then detected by a wide array of Ca(2+)
      binding effector proteins whose affinities are appropriately tuned to respond to
      a particular type of [Ca(2+)] change. This deceptively simple paradigm dominates
      the function of many cell types, for example in driving contraction of muscle,
      action potential generation in nerves, fluid, hormone, and enzyme secretion in
      secretory cells, and certain immune responses. However, the Ca(2+) signal does
      not work in strict isolation, but rather is fine-tuned by many other signals, not
      the least of which is the other major second messenger, cyclic AMP (cAMP).
      Conversely, the cAMP pathway is subject to modification by the calcium signal and
      its various effectors at many different levels. These two fundamental second
      messengers, used throughout eukaryotes and even prokaryotes, are thus
      inextricably intertwined. The purpose of the present article is to provide an
      update on some of the recently described forms of reciprocal regulation between
      Ca(2+) and cAMP signaling circuits, with emphasis on interactions that take place
      in localized domains of the cell.

PMID- 22963561
TI  - Calcium signaling in neuronal motility: pharmacological tools for investigating
      specific pathways.
AB  - Migration of neurons and neuronal precursors from the site of origin to their
      final location is a key process in the development of the nervous system and in
      the correct organization of neuronal structures and circuits. Different modes of
      migration (mainly radial and tangential) have been described in the last 40
      years; for these, as for motility processes involving other cellular types,
      calcium signaling plays a key role, with influx from the extracellular medium
      representing the main mechanism, and a more delimited but specific role played by
      release from intracellular stores. Deciphering the involvement of the different
      calcium influx pathways has been a major task for cellular neurobiologists, and
      the availability - or lack - of reliable and selective pharmacological tools has
      represented the main limiting factor. This review addresses the strategies
      employed to investigate the role of voltage-dependent calcium channels and of
      neurotransmitter activated channels, either calcium permeable or not, that
      directly or indirectly can elicit cytosolic calcium increases; in addition,
      reference to recent findings on the involvement of other families of calcium
      permeable channels (such as the transient receptor potential superfamily) is
      presented. Finally, a brief description of the present - and limited - knowledge
      of the perturbations of calcium signaling involved in neuronal migration
      pathologies is provided.

PMID- 22963562
TI  - Store-dependent Ca(2+) entry in endothelial progenitor cells as a perspective
      tool to enhance cell-based therapy and adverse tumour vascularization.
AB  - Endothelial progenitor cells (EPCs) have recently been employed in cell-based
      therapy (CBT) to promote neovascularization and regeneration of ischemic organs,
      such as heart and limbs. Furthermore, EPCs may be recruited from bone marrow by
      growing tumors to drive the angiogenic switch through physical engrafting into
      the lumen of nascent vessels or paracrine release of pro-angiogenic factors. CBT
      is hampered by the paucity of EPCs harvested from peripheral blood and suffered
      from several pitfalls, including the differentiation outcome of transplanted
      cells and low percentage of engrafted cells. Therefore, CBT will benefit from a
      better understanding of the signal transduction pathway(s) which govern(s) EPC
      homing, proliferation and incorporation into injured tissues. At the same time,
      this information might outline alternative molecular targets to combat tumoral
      neovascularization. We have recently found that store-operated Ca(2+) entry, a
      Ca(2+)-permeable membrane pathway that is activated upon depletion of the
      inositol-1,4,5-trisphosphate-sensitive Ca(2+) pool, is recruited by vascular
      endothelial growth factor to support proliferation and tubulogenesis in human
      circulating endothelial colony forming cells (ECFCs). ECFCs are a subgroup of
      EPCs that circulate in the peripheral blood of adult individuals and are able to
      proliferate and differentiate into endothelial cells and form capillary networks
      in vitro and contribute to neovessel formation in vivo. The present review will
      discuss the relevance of SOCE to ECFC-based cell therapy and will address the
      pharmacological inhibition of store-dependent Ca(2+) channels as a promising
      target for anti-angiogenic treatments.

PMID- 22963563
TI  - Regulation of intracellular cardiomyocyte calcium stores by peptides: a new
      approach to cardiac protection.
AB  - The control of cytosolic calcium is a major determinant not only of cardiac
      function, but also of the capability of myocardial tissue to survive damage.
      Increase of diastolic calcium leads rapidly to cell injury, and may be induced by
      a wide range of causes. In this review we describe the major points of calcium
      control in cardiac myocytes, mainly in mammalian ventricle, focusing on
      mechanisms of intracellular calcium influx during excitation, voltage gated
      channels of the sarcolemma and ryanodine receptors of the sarcoplasmic reticulum
      (SR), and efflux during relaxation, principally the sodium/calcium exchanger in
      membrane and the SR calcium complex. Mitochondria also depend on calcium
      concentration while also participating in its control. Moreover, we will outline
      receptor check points and their roles in physiology and pathology. We will focus
      on some new aspects of potential protective mechanisms that have been recently
      described and that involve peptide ligands and that in the case of the
      Neuregulin1beta/ErbB pathway are already reaching the clinical trial relevance.

PMID- 22963564
TI  - Intracellular calcium signaling: holding the balance between health and disease.

PMID- 22963565
TI  - Stem cell dynamics and heterogeneity: implications for epidermal regeneration and
      skin cancer.
AB  - The skin epithelium undergoes constant renewal, a process that is driven by stem
      cells (SCs) localising to the interfollicular epidermis and different regions of
      the hair follicle. Over the last years, tremendous progress has been made to
      unravel the physiological function of distinct stem and progenitor cell
      populations by using genetic lineage tracing in vivo, transplantation,
      clonogenicity approaches and live cell imaging. It turned out that these cell
      compartments constitute heterogeneous SC pools and that individual SCs respond
      differently to various signals sent by the microenvironment. Recent genetic
      manipulation experiments and elegant mouse models have shed light on the
      signalling pathways being crucial for self-renewal and lineage fate decisions
      during tissue homeostasis. Here, we summarise current concepts of SC function in
      mammalian skin and focus on the dynamic behaviour of SCs during morphogenesis and
      tissue regeneration of the skin epithelium. Clearly, understanding the cellular
      and molecular mechanisms of SC regulation and function during tissue homeostasis
      has enormous impact on our view of the pathogenesis of various skin diseases and
      will be beneficial for regenerative medicine. Recent experiments suggest an
      important role of tissue SCs in the process of skin tumour initiation and
      progression. For the future, the genuine challenge is to further dissect SC
      function in pathophysiological settings and to translate our knowledge to design
      novel efficient therapeutic strategies for treatment of cutaneous cancer.

PMID- 22963566
TI  - Targeting glioblastoma stem cells: cell surface markers.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumor and among
      the most lethal cancers. There is increasing evidence that cancer stem cells
      within GBMs, which are often referred to as glioblastoma stem cells (GSCs), play
      a critical role in tumor initiation and maintenance. Identification of novel
      markers for GSCs will lead to better targeting of GSCs which could have
      tremendous impact on treatment of GBMs. Cell surface markers are particularly
      suitable as therapeutic targets. Although several promising cell surface markers
      have successfully been used for enrichment of GSCs, their functional roles in
      maintenance of GSC properties as well as in GBM formation and development remain
      to be characterized. In this review, we primarily summarize recent advances in
      identification of GSC markers, with a particular focus on cell surface markers.

PMID- 22963567
TI  - The use of stem cells in regenerative medicine for Parkinson's and Huntington's
      Diseases.
AB  - Cell transplantation has been proposed as a means of replacing specific cell
      populations lost through neurodegenerative processes such as that seen in
      Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has
      been observed in a number of Parkinson and Huntington's patients transplanted
      with freshly isolated fetal brain tissue but such restorative approach is greatly
      hampered by logistic and ethical concerns relative to the use of fetal tissue, in
      addition to potential side effects that remain to be controlled. In this context,
      stem cells that are capable of self-renewal and can differentiate into neurons,
      have received a great deal of interest, as demonstrated by the numerous studies
      based on the transplantation of neural stem/progenitor cells, embryonic stem
      cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's
      diseases. More recently, the induction of pluripotent stem cells from somatic
      adult cells has raised a new hope for the treatment of neurodegenerative
      diseases. In the present article, we review the main experimental approaches to
      assess the efficiency of cell-based therapy for Parkinson's or Huntington's
      diseases, and discuss the recent advances in using stem cells to replace lost
      dopaminergic mesencephalic or striatal neurons. Characteristics of the different
      stem cells are extensively examined with a special attention to their ability of
      producing neurotrophic or immunosuppressive factors, as these may provide a
      favourable environment for brain tissue repair and long-term survival of
      transplanted cells in the central nervous system. Thus, stem cell therapy can be
      a valuable tool in regenerative medicine.

PMID- 22963568
TI  - Cardiac regeneration: stem cells and beyond.
AB  - After myocardial infarction, the lost healthy myocardium is replaced by non
      contractile scar tissue which may lead to the development of heart failure and
      death. There is no curative therapy for the irreversible myocardial cell loss.
      This review will give an overview of the current options to restore the
      contractile force of the heart: the different stem cell sources as therapeutic
      agents in cardiac repair as well as more novel approaches like the activation of
      endogenous cell populations, the use of paracrine factors and engineered heart
      tissue.

PMID- 22963569
TI  - Progress and pitfalls in the identification of cancer stem cell-targeting
      therapies in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent and deadly
      cancer that has not shown improvements in survival rates for many years. Current
      treatments of HNSCC include surgical resection, radiotherapy, and chemotherapy,
      which are relatively ineffective for the management of recurrent or metastatic
      tumors. Cancer stem cells (CSC) within HNSCC offer an attractive therapeutic
      target for improving the survival rates for such cases, as eliminating the cells
      responsible for tumor initiation will theoretically prevent the onset of
      metastasis and recurrence. Since CSCs were initially isolated from HNSCC, there
      have been a handful of papers published that examine the potential of certain
      agents to selectively inhibit HNSCC CSCs, although a review of these papers has
      not yet been performed. Here we review the current literature for potential
      compounds or particles which have been proposed to selectively target the HNSCC
      CSC subpopulation. The various agents that have been tested so far include RNA
      interference, cell-based immunotherapy, antibodies, chemicals, microRNA
      precursors, and lentiviral microRNA vectors. Although many of these compounds
      showed considerable promise, few, if any, of the studies provided comprehensive
      evidence showing that the proposed agents were specific to CSCs and were
      considerably more effective than conventional therapy (radiation, cisplatin,
      etc). The proposed treatments in these studies require further investigation in
      these two regards, especially through rigorous in vivo experimentation, before
      they can be considered as true potential CSC inhibitors, let alone be considered
      for use in clinical trials.

PMID- 22963570
TI  - Can breast cancer stem cells evade the immune system?
AB  - The evidence seems to be growing in favor of the stem cell theory of cancer with
      the emergence of studies demonstrating the parallel mechanisms of self renewing
      pathways in stem cells and particular subsets of cancer cells. The finding of
      leukemia stem cells and subsequently breast cancer stem cells (BCSC) further
      supports the concept. The importance of these findings lends itself to the
      selfrenewal properties of stem cells in addition to the survival characteristics
      of stem cells, mechanisms that will have to be overcome when creating treatment
      modalities. In particular, research has shown that stem cells and a specific type
      of stem cells, mesenchymal stem cells (MSC), have special drug effluxing
      properties and some interactions with particular cells of the immune system that
      may serve major roles in immunosuppresion and overall tumor cell survival.
      Furthermore, the recent discovery of epithelial to mesenchymal transition (EMT)
      has laid out a possible mechanism for tumor cells to lose particular phenotypic
      epithelial cell markers and gain phenotypic mesenchymal cell markers. This
      process is implicated in metastasis in addition to overall tumor survival and
      evasion of the immune system. This review examines the current understanding of
      how tumor cells evade the immune system, but will first explore stem cells,
      cancer stem cells, normal immune interaction with tumor cells, and EMT.

PMID- 22963571
TI  - Stem cell niche in tissue homeostasis, aging and cancer.
AB  - Stem cells have an essential role in tissue homeostasis, repair, and regeneration
      of a tissue or an organ. Stem cells are immature cells having unlimited ability
      of self-renewal and capacity to differentiate into specialized cell types. Proper
      regulation of these dual properties is critical in animal development, growth
      control, and reproduction. Accumulating evidences suggest that stem cell behavior
      is regulated by both extracellular signals from the niche cells and intrinsic
      signal within stem cells. Using diverse model systems, tremendous work has been
      done to understand how niche control the stem cell self-renewal and
      differentiation. This review presents the progress made in stem cell niche field
      in germline and somatic stem cells in lower organism and mammals. The knowledge
      gained by studying the stem cells and its niches in diverse model organisms and
      the molecular mechanisms regulate their behavior are vital in understanding
      tissue homeostasis, regeneration, aging and cancer in humans.

PMID- 22963572
TI  - Stem cells in kidney regeneration.
AB  - Currently many efforts are being made to apply regenerative medicine to kidney
      diseases using several types of stem/progenitor cells, such as mesenchymal stem
      cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent
      stem cells. Stem cells have the ability to repair injured organs and ameliorate
      damaged function. The strategy for kidney tissue repair is the recruitment of
      stem cells and soluble reparative factors to the kidney to elicit tissue repair
      and the induction of dedifferentiation of resident renal cells. On the other
      hand, where renal structure is totally disrupted, absolute kidney organ
      regeneration is needed to rebuild a whole functional kidney. In this review, we
      describe current advances in stem cell research for kidney tissue repair and de
      novo organ regeneration.

PMID- 22963573
TI  - Stem cells, self-renewal and cancer of the gastric epithelium.
AB  - The gastric mucosa and its glands show continuous bidirectional self-renewal via
      differentiation from stem and progenitor cells. Here, two types of gastric units,
      i.e., fundic and antral units, form delicate homeostatic systems. This review
      focuses on recent developments concerning the different types of gastric stem
      cells, the central function of parietal cells as organizing centres of fundic
      units, the stepwise differentiation of zymogenic cells via trans-differentiation
      of mucous neck cells, and unexpected differences between fundic and antral
      surface mucous cells. Within the last years, the central role of Sonic hedgehog
      (Shh) for correct self-renewal of fundic units has become much clearer.
      Furthermore, also the knowledge concerning the genesis of gastric cancer
      increased substantially. Here, chronic inflammation leads to dysregulated
      differentiation processes and finally to cancer. Remarkable progress has been
      made particularly concerning the genesis of two metaplastic cell lineages, i.e.,
      the TFF2/spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal
      metaplasia, which both arise in intestinal-type cancers in fundic units by
      dysregulated trans-differentiation of the zymogenic cell lineage. Additionally,
      Shh has been recognized as a target for inflammatory processes and an important
      player for innate immunity processes. Thus, stem cells, self-renewal, and gastric
      cancer are intimately linked.

PMID- 22963574
TI  - Editorial: stem cells in regenerative medicine and cancer.

PMID- 22963576
TI  - Effects of traumatic stress and perceived stress on everyday cognitive
      functioning.
AB  - Stressful or traumatic events have been shown to impair cognitive functioning on
      laboratory-based tasks due to stress-related intrusive thoughts and avoidance.
      However, research on the effects of stress on everyday cognitive functioning has
      been lacking. A sample of 909 undergraduates completed measures of perceived
      stress, PTSD symptoms, and everyday cognitive failures. The results revealed that
      both perceived stress and PTSD symptoms uniquely predicted cognitive failures,
      even after controlling for a number of potentially confounding variables.
      Additionally, there was a significant interaction. Participants with low scores
      on both measures of stress reported the fewest occurrences of everyday cognitive
      failures. In contrast, participants with elevated scores on either measure of
      stress reported higher levels of cognitive failures. These results suggest that
      there are unique negative effects of perceived stress and PTSD symptoms on
      everyday cognitive functioning and sharpen our understanding of the relationship
      between stress and cognition.

PMID- 22963575
TI  - Emotional responding in depression: distinctions in the time course of emotion.
AB  - The current studies were designed to investigate if the emotion context
      insensitivity hypothesis (ECI; Rottenberg & Gotlib, 2004) is applicable across
      the time course of emotion. Recent affective science research has pointed to the
      importance of considering anticipation and maintenance of emotion. In the current
      studies, we assessed emotion responses among college students with depression
      symptoms in anticipation of, during, and after an emotional picture using the
      emotion modulated startle paradigm. People with and without depression symptoms
      did not differ in blink magnitude in anticipation of emotional pictures
      suggesting that some anticipatory processes may not be impaired by depression
      symptoms. In contrast, individuals with depression symptoms did not exhibit blink
      magnitudes that varied by valence, either during viewing or after the pictures
      were removed from view. These findings suggest that ECI is relevant not only for
      those diagnosed with major depressive disorder, but also for people with
      depression symptoms that may not cross the diagnostic threshold. These data also
      point to the importance of considering the time course of emotion to better
      understand emotional deficits in individuals with differing levels of depression
      symptoms. Identifying where emotion goes awry across the time course of emotion
      can help inform treatment development.

PMID- 22963577
TI  - The place of volition in addiction: differing approaches and their implications
      for policy and service provision.
AB  - INTRODUCTION: 'Addiction' is an ambiguous concept. Its meaning, and how it is
      used in drug policy and treatment, depends on how it is conceptualised. While the
      'disease' model of addiction is prevalent in Australia, differing, sometimes
      contradictory, interpretations of this model are mobilised. METHODS: Drawing on
      20 semi-structured interviews conducted with professionals working in the area of
      drug use in Victoria, Australia, this paper develops a typology delineating
      different approaches to addiction. RESULTS: Five domains of meaning related to
      addiction were identified in the data. These were: (i) the sign of craving; (ii)
      susceptibility; (iii) social and psychological issues producing addiction; (iv)
      self-concept; and (v) social functions of addiction. These domains are further
      divided into two subtypes based on how the participants understood the role of a
      key notion in addiction: volition, that is, whether or not an 'addict' has
      control over drug use and other aspects of life. DISCUSSION: By systematically
      mapping different conceptualisations of addiction, this typology identifies the
      ambiguities and contradictions in the models currently in use, especially with
      respect to the notion of volition. While a homogeneous approach to these issues
      is neither practical nor desirable, there is a need to consider the implications
      of this lack of coherence. CONCLUSIONS: Service providers, medical practitioners
      and policy makers need to reflect on their assumptions, and consider the
      implications of their different approaches for clients, some of whom encounter
      more than one approach when undergoing treatment for drug use.

PMID- 22963578
TI  - Enteropathy-associated T-cell lymphoma, lacking MHC class II, with immune
      privileged site recurrence, presenting as bilateral ocular vitreous humour
      involvement - a case report.

PMID- 22963579
TI  - The complete mitochondrial DNA genome of a greater horseshoe bat subspecies,
      Rhinolophus ferrumequinum quelpartis (Chiroptera: Rhinolophidae).
AB  - There are two subspecies of Rhinolophus ferrumequinum currently recognized in
      South Korea. The Korean greater horseshoe bat subspecies, Rhinolophus
      ferrumequinum quelpartis, is distributed only in Jeju Island. The complete
      mitochondrial genome of the island subspecies was determined and revealed 99.7%
      similarity to the mainland subspecies Rhinolophus ferrumequinum korai. If d-loop
      region is excluded, similarity of the two genomes was 99.9%.

PMID- 22963580
TI  - Transcriptome analysis of rice root responses to potassium deficiency.
AB  - BACKGROUND: Potassium (K+) is an important nutrient ion in plant cells and plays
      crucial roles in many plant physiological and developmental processes. In the
      natural environment, K+ deficiency is a common abiotic stress that inhibits plant
      growth and reduces crop productivity. Several microarray studies have been
      conducted on genome-wide gene expression profiles of rice during its responses to
      various stresses. However, little is known about the transcriptional changes in
      rice genes under low-K+ conditions. RESULTS: We analyzed the transcriptomic
      profiles of rice roots in response to low-K+ stress. The roots of rice seedlings
      with or without low-K+ treatment were harvested after 6 h, and 3 and 5 d, and
      used for microarray analysis. The microarray data showed that many genes (2,896)
      were up-regulated or down-regulated more than 1.2-fold during low-K+ treatment.
      GO analysis indicated that the genes showing transcriptional changes were mainly
      in the following categories: metabolic process, membrane, cation binding, kinase
      activity, transport, and so on. We conducted a comparative analysis of
      transcriptomic changes between Arabidopsis and rice under low-K+ stress.
      Generally, the genes showing changes in transcription in rice and Arabidopsis in
      response to low-K+ stress displayed similar GO distribution patterns. However,
      there were more genes related to stress responses and development in Arabidopsis
      than in rice. Many auxin-related genes responded to K+ deficiency in rice,
      whereas jasmonic acid-related enzymes may play more important roles in K+
      nutrient signaling in Arabidopsis. CONCLUSIONS: According to the microarray data,
      fewer rice genes showed transcriptional changes in response to K+ deficiency than
      to phosphorus (P) or nitrogen (N) deficiency. Thus, transcriptional regulation is
      probably more important in responses to low-P and -N stress than to low-K+
      stress. However, many genes in some categories (protein kinase and ion
      transporter families) were markedly up-regulated, suggesting that they play
      important roles during K+ deficiency. Comparative analysis of transcriptomic
      changes between Arabidopsis and rice showed that monocots and dicots share many
      similar mechanisms in response to K+ deficiency, despite some differences.
      Further research is required to clarify the differences in transcriptional
      regulation between monocots and dicots.

PMID- 22963581
TI  - CO2, NOx, and particle emissions from aircraft and support activities at a
      regional airport.
AB  - The goal of this research was to quantify emissions of carbon dioxide (CO(2)),
      nitrogen oxides (NO(x)), particle number, and black carbon (BC) from in-use
      aircraft and related activity at a regional airport. Pollutant concentrations
      were measured adjacent to the airfield and passenger terminal at the Roanoke
      Regional Airport in Virginia. Observed NO(x) emission indices (EIs) for jet
      powered, commuter aircraft were generally lower than those contained in the
      International Civil Aviation Organization databank for both taxi (same as idle)
      and takeoff engine settings. NO(x) EIs ranged from 1.9 to 3.7 g (kg fuel)(-1)
      across five types of aircraft during taxiing, whereas EIs were consistently
      higher, 8.8-20.6 g (kg fuel)(-1), during takeoff. Particle number EIs ranged from
      1.4 * 10(16) to 7.1 * 10(16) (kg fuel)(-1) and were slightly higher in taxi mode
      than in takeoff mode for four of the five types of aircraft. Diurnal patterns in
      CO(2) and NO(x) concentrations were influenced mainly by atmospheric conditions,
      while patterns in particle number concentrations were attributable mainly to
      patterns in aircraft activity. CO(2) and NO(x) fluxes measured by eddy covariance
      were higher at the terminal than at the airfield and were lower than found in
      urban areas.

PMID- 22963582
TI  - Effects of Ramadan fasting on cardiovascular risk factors: a prospective
      observational study.
AB  - BACKGROUND: Previous research has shown that Ramadan fasting has beneficial
      effects on cardiovascular risk factors, however there are controversies. In the
      present study, the effect of Ramadan fasting on cardiovascular risk factors has
      been investigated. METHOD: This is a prospective observational study that was
      carried out in a group of patients with at least one cardiovascular risk factor
      (including history of documented previous history of either coronary artery
      disease (CAD), metabolic syndrome or cerebro-vascular disease in past 10 y).
      Eighty two volunteers including 38 male and 44 female, aged 29-70 y, mean 54.0 +/
      10 y, with a previous history of either coronary artery disease, metabolic
      syndrome or cerebro-vascular disease were recruited. Subjects attended the
      metabolic unit after at least 10 h fasting, before and after Ramadan who were
      been fasting for at least 10 days. A fasting blood sample was obtained, blood
      pressure was measured and body mass index (BMI) was calculated. Lipids profile,
      fasting blood sugar (FBS) and insulin, homocysteine (hcy), high-sensitivity C
      reactive protein (hs-CRP) and complete blood count (CBC) were analyzed on all
      blood samples. RESULTS: A significant improvement in 10 years coronary heart
      disease risk (based on Framingham risk score) was found (13.0 +/- 8 before
      Ramadan and 10.8 +/-7 after Ramadan, P <0.001, t test).There was a significant
      higher HDL-c, WBC, RBC and platelet count (PLT), and lower plasma cholesterol,
      triglycerides, LDL-c, VLDL-c, systolic blood pressure, body mass index and waist
      circumference after Ramadan (P <0.05, t test). The changes in FBS, insulin,
      Homeostasis Model Assessment Insulin Resistance (HOMA-IR), hcy, hs-CRP and
      diastolic blood pressure before and after Ramadan were not significant (P >0.05,
      t test). CONCLUSIONS: This study shows a significant improvement in 10 years
      coronary heart disease risk score and other cardiovascular risk factors such as
      lipids profile, systolic blood pressure, weight, BMI and waist circumference in
      subjects with a previous history of cardiovascular disease.

PMID- 22963583
TI  - A field survey on the presence of prednisolone and prednisone in urine samples
      from untreated cows.
AB  - Prednisolone is a synthetic glucocorticoid widely employed in bovine clinical
      practice that may also be used illegally as a growth promoter. Recent in vitro
      and in vivo studies lend support to the hypothesis that prednisolone could be
      synthesised from cortisol in untreated cattle subjected to stressful events. To
      verify such a hypothesis, a field survey was conducted on urine samples collected
      from 131 guaranteed untreated cows and analysed for the presence of prednisolone
      and prednisone - in some instances also for cortisol and cortisone - with a
      validated LC/MS-MS method. None of the examined samples exhibited either
      prednisolone levels higher than the CCalpha limit (around 0.70 ug l-1) or
      prednisone, being therefore officially compliant for both analytes. Trace amounts
      of prednisolone, approximately estimated in the range 0.1-0.3 ug l-1 were found
      in only seven samples from cows also showing urinary cortisol and cortisone
      levels higher than those detected in negative specimens, as the result of a
      probable stress condition.

PMID- 22963584
TI  - Bat rabies surveillance in Europe.
AB  - Rabies is the oldest known zoonotic disease and was also the first recognized bat
      associated infection in humans. To date, four different lyssavirus species are
      the causative agents of rabies in European bats: the European Bat Lyssaviruses
      type 1 and 2 (EBLV-1, EBLV-2), the recently discovered putative new lyssavirus
      species Bokeloh Bat Lyssavirus (BBLV) and the West Caucasian Bat Virus (WCBV).
      Unlike in the new world, bat rabies cases in Europe are comparatively less
      frequent, possibly as a result of varying intensity of surveillance. Thus, the
      objective was to provide an assessment of the bat rabies surveillance data in
      Europe, taking both reported data to the WHO Rabies Bulletin Europe and published
      results into account. In Europe, 959 bat rabies cases were reported to the RBE in
      the time period 1977-2010 with the vast majority characterized as EBLV-1,
      frequently isolated in the Netherlands, North Germany, Denmark, Poland and also
      in parts of France and Spain. Most EBLV-2 isolates originated from the United
      Kingdom (UK) and the Netherlands, and EBLV-2 was also detected in Germany,
      Finland and Switzerland. Thus far, only one isolate of BBLV was found in Germany.
      Published passive bat rabies surveillance comprised testing of 28 of the 52
      different European bat species for rabies. EBLV-1 was isolated exclusively from
      Serotine bats (Eptesicus serotinus and Eptesicus isabellinus), while EBLV-2 was
      detected in 14 Daubenton's bats (Myotis daubentonii) and 5 Pond bats (Myotis
      dasycneme). A virus from a single Natterer's bat (Myotis nattereri) was
      characterized as BBLV. During active surveillance, only oral swabs from 2
      Daubenton's bats (EBLV-2) and from several Eptesicus bats (EBLV-1) yielded virus
      positive RNA. Virus neutralizing antibodies against lyssaviruses were detected in
      various European bat species from different countries, and its value and
      implications are discussed.

PMID- 22963585
TI  - Release of endogenous opioids during a chronic IBD model suppresses the
      excitability of colonic DRG neurons.
AB  - BACKGROUND: Endogenous opioids are implicated in pain-regulation in chronic
      inflammatory bowel disease (IBD). We sought to examine whether endogenous opioids
      suppress the excitability of colonic nociceptive dorsal root ganglia (DRG)
      neurons during chronic IBD, and if so, whether modulation of underlying voltage
      gated K(+) currents was involved. METHODS: The effects of chronic dextran sulfate
      sodium (DSS) colitis on afferent signaling in mice was studied using patch clamp
      recordings. Colonic DRG neurons were identified using Fast Blue retrograde
      labeling and recordings obtained from small DRG neurons (<40 pF). KEY RESULTS: In
      current-clamp recordings, the rheobase of neurons was increased 47% (P < 0.01)
      and action potential discharge at twice rheobase decreased 23% (P < 0.05)
      following incubation in colonic supernatants from chronic DSS mice. beta
      endorphin increased 14-fold, and tissue opioid immunoreactivity and expression in
      CD4+ cells observed by flow cytometry increased in chronic DSS colons. Incubation
      of naive neurons in the MU-opioid receptor agonist D-Ala(2), N- MePhe(4), Gly-ol
      (DAMGO) (10 nM) partially recapitulated the effects of supernatants from DSS mice
      on rheobase. Supernatant effects were blocked by the MU-opioid receptor
      antagonist naloxone. In voltage clamp, chronic DSS supernatants and DAMGO
      increased I(A) K(+) currents. CONCLUSIONS & INFERENCES: The release of endogenous
      opioids during chronic inflammation in mice suppresses the excitability of
      nociceptive DRG neurons. Targeting immune cells may provide a novel means of
      modulating IBD pain.

PMID- 22963586
TI  - Respiratory syncytial virus infection and chronic respiratory morbidity - is
      there a functional or genetic predisposition?
AB  - A systematic literature review has been undertaken. Respiratory syncytial virus
      (RSV) lower respiratory tract infection (LRTI) in infancy is associated with
      chronic respiratory morbidity. Premorbid abnormal lung function may predispose to
      RVS LRTI in prematurely born infants. CONCLUSION:   Single-nucleotide
      polymorphisms in genes coding for IL-8, IL-19, IL-20, IL-13 mannose-binding
      lectin, IFNG and a RANTES polymorphism have been associated with subsequent
      wheeze following RSV LRTI in term-born infants.

PMID- 22963587
TI  - Regulation of Toll-like receptor 2 interaction with Ecgp96 controls Escherichia
      coli K1 invasion of brain endothelial cells.
AB  - The interaction of outer membrane protein A (OmpA) with its receptor, Ecgp96 (a
      homologue of Hsp90beta), is critical for the pathogenesis of Escherichia coli K1
      meningitis. Since Hsp90 chaperones Toll-like receptors (TLRs), we examined the
      role of TLRs in E. coli K1 infection. Herein, we show that newborn TLR2(-/-) 
      mice are resistant to E. coli K1 meningitis, while TLR4(-/-)  mice succumb to
      infection sooner. In vitro, OmpA+ E. coli infection selectively upregulates
      Ecgp96 and TLR2 in human brain microvascular endothelial cells (HBMEC), whereas
      OmpA- E. coli upregulates TLR4 in these cells. Furthermore, infection with OmpA+
      E. coli causes Ecgp96 and TLR2 translocate to the plasma membrane of HBMEC as a
      complex. Immunoprecipitation studies of the plasma membrane fractions from
      infected HBMEC reveal that the C termini of Ecgp96 and TLR2 are critical for
      OmpA+ E. coli invasion. Knockdown of TLR2 using siRNA results in inefficient
      membrane translocation of Ecgp96 and significantly reduces invasion. In addition,
      the interaction of Ecgp96 andTLR2 induces a bipartite signal, one from Ecgp96
      through PKC-alpha while the other from TLR2 through MyD88, ERK1/2 and NF-kappaB.
      This bipartite signal ultimately culminates in the efficient production of NO,
      which in turn promotes E. coli K1 invasion of HBMEC.

PMID- 22963588
TI  - The effect of exercise on prescription on physical activity and wellbeing in a
      multi-ethnic female population: A controlled trial.
AB  - BACKGROUND: In Western countries, individuals from multi-ethnic disadvantaged
      populations are less physically active than the Western population as a whole.
      This lack of physical activity (PA) may be one of the factors explaining
      disparities in health. Exercise on Prescription" (EoP), is an exercise program to
      which persons are referred by primary care. It has been developed to suit the
      needs of physically inactive women from diverse ethnic backgrounds living in
      deprived neighborhoods in the Netherlands. The effectiveness of this program has
      however, not yet been proven. METHODS: A total of 514 women from diverse ethnic
      backgrounds were included in this study (192 EoP, 322 control group). Women in
      the EoP group participated in 18 sessions of supervised PA. The control group
      received care as usual. At baseline, 6 and 12 months the women attended an
      interview and a physical examination. Outcome measures were PA, BMI, weight
      circumference, fat percentage, oxygen uptake, mental well-being, subjective
      health and use of care. RESULTS: Of the participants 59% had a low educational
      level and 90% of the women were overweight or obese. Compliance was high, only
      14% dropped out during the course of the program. Total PA did not change, PA
      during leisure time increased at 6 and at 12 months and PA during household
      activities increased at 12 months (PEoPvsControl < 0.05). EoP had no significant
      effect on the other outcome variables. CONCLUSIONS: EoP was successful in
      recruiting its target population and compliance was high. The effect of EoP on
      PA, health and mental well-being was limited. In this format EoP does not seem to
      be effective for increasing PA and the health status of non-Western migrant
      women. TRIAL REGISTRATION: Dutch Trial register: NTR1294.

PMID- 22963589
TI  - Clinical governance implementation in a selected teaching emergency department: a
      systems approach.
AB  - BACKGROUND: Clinical governance (CG) is among the different frameworks proposed
      to improve the quality of healthcare. Iran, like many other countries, has put
      healthcare quality improvement in its top health policy priorities. In November
      2009, implementation of CG became a task for all hospitals across the country.
      However, it has been a challenge to clarify the notion of CG and the way to
      implement it in Iran. The purpose of this action research study is to understand
      how CG can be defined and implemented in a selected teaching emergency department
      (ED). METHODS/DESIGN: We will use Soft Systems Methodology for both designing the
      study and inquiring into its content. As we considered a complex problem
      situation regarding the quality of care in the selected ED, we initially
      conceptualized CG as a cyclic set of purposeful activities designed to explore
      the situation and find relevant changes to improve the quality of care. Then,
      implementation of CG will conceptually be to carry out that set of purposeful
      activities. The activities will be about: understanding the situation and finding
      out relevant issues concerning the quality of care; exploring different
      stakeholders' views and ideas about the situation and how it can be improved; and
      defining actions to improve the quality of care through structured debates and
      development of accommodations among stakeholders. We will flexibly use
      qualitative methods of data collection and analysis in the course of the study.
      To ensure the study rigor, we will use different strategies. DISCUSSION:
      Successful implementation of CG, like other quality improvement frameworks,
      requires special consideration of underlying complexities. We believe that
      addressing the complex situation and reflections on involvement in this action
      research will make it possible to understand the concept of CG and its
      implementation in the selected setting. By describing the context and executed
      flexible methods of implementation, the results of this study would contribute to
      the development of implementation science and be employed by boards and
      executives governing other clinical settings to facilitate CG implementation.

PMID- 22963590
TI  - Re-evaluating the effect of harvesting regimes on Nile crocodiles using an
      integral projection model.
AB  - Crocodile populations are size-structured, and for populations that are subject
      to harvesting, removal is typically size selective. For this reason, size
      structured matrix models are typically used to analyse the dynamics of crocodile
      populations. The boundaries between the size classes used to classify individuals
      in these models are typically chosen arbitrarily. This is problematic because
      results can depend upon the number and width of size classes. The recent
      development of continuous character population models termed integral projection
      models (IPM) has removed the need to arbitrarily classify individuals. These
      models are yet to be applied to harvested animal populations. Using information
      obtained from the literature, we develop an IPM for crocodiles. We use
      perturbation analyses to investigate how altering size-specific demographic rates
      influences the population growth rate and the strength of selection on snout to
      vent length. We find that perturbations can lead to complex responses.
      Sensitivity analysis to population growth and fertility selection reveals that
      the smallest animals and the sizes of early breeding individuals and their eggs
      may have more influence on these population biology parameters than previously
      thought. Although our model is relatively simple, our results show that IPM can
      be used to gain theoretical insight into the possible consequences of altering
      size-specific demographic rates on the population and evolutionary ecology of
      harvested populations.

PMID- 22963592
TI  - Agreement between therapists, parents, patients, and independent evaluators on
      clinical improvement in pediatric obsessive-compulsive disorder.
AB  - OBJECTIVE: Independent evaluators (IE) are used widely in clinical trials to make
      unbiased determinations of treatment response. By virtue of being kept blind to
      treatment condition, however, IEs are also kept unaware of many pertinent
      clinical details that are relevant for decisions about clinical improvement. In
      this study, agreement among raters (children, parents, therapists, and IEs) about
      treatment response over the course of a 14-week clinical trial for pediatric
      obsessive-compulsive disorder (OCD) was examined in order to determine the
      utility of nonblind clinician and patient ratings of treatment response. METHOD:
      Participants were 71 youth (mean age = 12.2 years; 63.4% female) with a primary
      diagnosis of OCD and their parents participating in a psychotherapy trial. IEs
      provided response ratings (Clinician's Global Impressions-Improvement Scale; CGI
      I) at Weeks 4, 8, and 14, and therapists, children, and parents completed
      independent CGI-I ratings at Weeks 2, 4, 8, and 14. RESULTS: Nonlinear mixed
      models revealed differences in rating parties, with therapists and IEs slower to
      rate treatment improvement compared with children and parents, and growth curve
      models suggested that therapists and IEs produced generally consistent ratings.
      In addition, no evidence was found for an Evaluator * Treatment interaction,
      indicating that raters displayed these differences consistently across both
      active and placebo conditions. CONCLUSIONS: Youth and parents may be able to
      provide accurate ratings of global improvement; nonblinded treating clinicians
      (with training in research-oriented assessment) can offer global improvement
      ratings commensurate with blinded IEs. Findings suggest that alternatives (or
      additions) to the blinded-IE model may be appropriate for assessing global
      improvement, especially with the growing emphasis on dissemination and
      effectiveness trials.

PMID- 22963593
TI  - Relations of alcohol consumption with smoking cessation milestones and tobacco
      dependence.
AB  - OBJECTIVE: Alcohol consumption is associated with smoking cessation failure in
      both community and clinical research. However, little is known about the relation
      between alcohol consumption and smoking cessation milestones (i.e., achieving
      initial abstinence, avoiding lapses and relapse). Our objective in this research
      was to examine the relations between pretreatment alcohol consumption patterns
      (non/infrequent drinker, moderate drinker, binge drinker) and smoking cessation
      milestones and tobacco dependence. METHOD: Data were collected from 1,504 smokers
      (58.2% women; 83.9% White; mean age = 44.67 years, SD = 11.08) making an aided
      smoking cessation attempt as part of a clinical trial. Alcohol consumption
      pattern was determined with the Composite International Diagnostic Interview.
      Tobacco dependence was assessed with the Wisconsin Inventory of Smoking
      Dependence Motives (WISDM). RESULTS: Alcohol consumption pattern was
      significantly associated with initial cessation and lapse, and these findings
      remained after controlling for the effects of treatment, race, gender, and
      cigarettes per day. Relative to moderate drinkers, both non/infrequent drinkers
      and binge drinkers were less likely to achieve initial cessation (p < .05), and
      binge drinkers were more likely to lapse (p < .01). When drinking categories were
      compared on tobacco dependence indices, results showed that relative to moderate
      drinkers, non/infrequent drinkers scored higher on several WISDM Primary
      Dependence Motives subscales (Tolerance, Loss of Control, and Automaticity) and
      binge drinkers scored higher on WISDM Secondary Dependence Motives subscales (Cue
      Exposure and Social-Environmental Goads). CONCLUSIONS: Non/infrequent drinkers'
      smoking cessation difficulties may be particularly related to core features of
      tobacco dependence, whereas binge drinkers' difficulties may be related to
      environmental and social influences.

PMID- 22963591
TI  - Psychological factors associated with head and neck cancer treatment and
      survivorship: evidence and opportunities for behavioral medicine.
AB  - Individuals diagnosed with head and neck cancer (HNC) not only face a potentially
      life-threatening diagnosis but must endure treatment that often results in
      significant, highly visible disfigurement and disruptions of essential
      functioning, such as deficits or complications in eating, swallowing, breathing,
      and speech. Each year, approximately 650,000 new cases are diagnosed, making HNC
      the 6th most common type of cancer in the world. Despite this, however, HNC
      remains understudied in behavioral medicine. In this article, the authors review
      available evidence regarding several important psychosocial and behavioral
      factors associated with HNC diagnosis, treatment, and recovery, as well as
      various psychosocial interventions conducted in this patient population, before
      concluding with opportunities for behavioral medicine research and practice.

PMID- 22963594
TI  - Translating basic behavioral and social science research to clinical application:
      the EVOLVE mixed methods approach.
AB  - OBJECTIVE: To describe a mixed-methods approach to develop and test a basic
      behavioral science-informed intervention to motivate behavior change in 3 high
      risk clinical populations. Our theoretically derived intervention comprised a
      combination of positive affect and self-affirmation (PA/SA), which we applied to
      3 clinical chronic disease populations. METHOD: We employed a sequential mixed
      methods model (EVOLVE) to design and test the PA/SA intervention in order to
      increase physical activity in people with coronary artery disease (post
      percutaneous coronary intervention [PCI]) or asthma (ASM) and to improve
      medication adherence in African Americans with hypertension (HTN). In an initial
      qualitative phase, we explored participant values and beliefs. We next pilot
      tested and refined the intervention and then conducted 3 randomized controlled
      trials with parallel study design. Participants were randomized to combined PA/SA
      versus an informational control and were followed bimonthly for 12 months,
      assessing for health behaviors and interval medical events. RESULTS: Over 4.5
      years, we enrolled 1,056 participants. Changes were sequentially made to the
      intervention during the qualitative and pilot phases. The 3 randomized controlled
      trials enrolled 242 participants who had undergone PCI, 258 with ASM, and 256
      with HTN (n = 756). Overall, 45.1% of PA/SA participants versus 33.6% of
      informational control participants achieved successful behavior change (p =
      .001). In multivariate analysis, PA/SA intervention remained a significant
      predictor of achieving behavior change (p < .002, odds ratio = 1.66), 95% CI
      [1.22, 2.27], controlling for baseline negative affect, comorbidity, gender,
      race/ethnicity, medical events, smoking, and age. CONCLUSIONS: The EVOLVE method
      is a means by which basic behavioral science research can be translated into
      efficacious interventions for chronic disease populations.

PMID- 22963595
TI  - A comparison of cognitive bias modification for interpretation and computerized
      cognitive behavior therapy: effects on anxiety, depression, attentional control,
      and interpretive bias.
AB  - OBJECTIVE: Computerized cognitive behavioral therapy (cCBT) and cognitive bias
      modification for interpretation (CBM-I) both have demonstrated efficacy in
      alleviating social anxiety, but how they compare with each other has not been
      investigated. The present study tested the prediction that both interventions
      would reduce anxiety relative to a no-intervention comparison condition, but CBM
      I would be particularly effective at modifying threat-related cognitive bias
      under high mental load. METHOD: Sixty-three primarily Caucasian adults (mean age
      = 22.7, SD = 5.87; 68.3% female) with high social anxiety, randomly allocated to
      3 groups: CBM-I (n = 21), cCBT (n = 21), and a no-intervention control group (n =
      21) provided complete data for analysis. Pre- and postintervention (4 sessions
      lasting 2 weeks, control participants only attended the pre-post sessions) self
      report measures of anxiety, depression, attentional control, and threat-related
      interpretive bias were completed. In addition, interpretive bias under high
      versus low cognitive load was measured using the Scrambled Sentences Test.
      RESULTS: Both CBM-I and cCBT groups reported significantly reduced levels of
      social anxiety, trait anxiety, and depression and improved attentional control,
      relative to the control group, with no clear superiority of either active
      intervention. Although both active conditions reduced negative bias on the
      Scrambled Sentences Test completed under mental load, CBM-I was significantly
      more effective at doing so. CONCLUSIONS: The results suggest that although not
      differing in therapeutic efficacy, CBM-I and cCBT might differ in the resilience
      of their effects when under mental load.

PMID- 22963596
TI  - Immunoglobulin G deposition to nonhemidesmosomal lamina lucida and early
      neutrophil involvement are characteristic features in a case of anti-p200
      pemphigoid.
AB  - The ultrastructural characteristics and immunolocalization of in vivo bound
      immunoglobulin G (IgG) in skin affected by anti-p200 pemphigoid have not been
      elucidated. To give insight into the mechanism of blister formation we report a
      new case of anti-p200 pemphigoid, studied with stage-oriented morphological
      analysis and immunoelectron microscopy. Skin biopsy specimens were evaluated
      ultrastructurally and histologically with immunohistochemistry. By observing the
      nonblister site, the blister edge and centre of the blister, we determined that
      neutrophil infiltration increases gradually at the dermoepidermal junction in
      association with the destruction of type IV collagen. Ultrastructurally, many
      neutrophils were observed under the lamina densa, with vacuole formation in the
      dermis. At the periphery of the blister, the lamina densa became fragmented and
      was observed either at the roof or the floor of the blister. At the centre of the
      blister, the lamina densa was mainly observed at the blister floor. Postembedding
      immunoelectron microscopy demonstrated that the IgG, bound in vivo, localized at
      the lamina lucida, while the area beneath the hemidesmosomes was spared. Together
      with the early involvement of neutrophils and the destruction of the basal
      lamina, we suggest that the binding of autoantibodies to the nonhemidesmosomal
      lamina lucida may induce inflammation with neutrophils, resulting in blister
      formation.

PMID- 22963598
TI  - Mediterranean species of the spittlebug genus Philaenus: modes of chromosome
      evolution.
AB  - The evolution of karyotypes and sex determination system of Philaenus Stal
      (Auchenorrhyncha: Aphrophoridae) species is studied here in detail. The most
      plausible scenario of chromosomal rearrangements accompanying phylogenetic
      differentiation in Philaenus is advanced. It is postulated that the ancestral
      karyotype of Philaenus was 2n = 24 + X0. Karyotype changes occurred several times
      independently in the genus. The karyotype of 2n = 22 + X0 (P. spumarius and P.
      tesselatus) originated from 2n = 24 + X0 by fusion between two autosomal pairs.
      The neo-XY system (P. arslani, P. loukasi, P. signatus, P. maghresignus, and P.
      tarifa) also originated from the 24 + X0 karyotype by means of independent
      fusions between autosomes and the original X chromosome. The neo-X(1)X(2)Y system
      (P. italosignus) evolved from the 2n = 22 + neo-XY karyotype by an additional
      fusion between the Y chromosome and one more autosomal pair. The neo-X(n)Y system
      of P. italosignus is the first reported case of an evolutionarily fixed multiple
      sex chromosome system in Auchenorrhyncha.

PMID- 22963597
TI  - Differential uptake of chemically modified cowpea mosaic virus nanoparticles in
      macrophage subpopulations present in inflammatory and tumor microenvironments.
AB  - There remains a tremendous need to develop targeted therapeutics that can both
      image and localize the toxic effects of chemotherapeutics and antagonists on
      diseased tissue while reducing adverse systemic effects. These needs have
      fostered the development of a nanotechnology-based approach that can combine
      targeting and toxicity potential. In this study, CPMV nanoparticles were
      chemically modified with the dye Alexa Flour 488 and were also tandemly modified
      with PEG1000 followed by AF488; and the derivatized nanoparticles were
      subsequently added to macrophages stimulated with either LPS (M1) or IL-4 (M2).
      Previously published studies have shown that M1/M2 macrophages are both present
      in an inflammatory microenvironment (such as a tumor microenvironment and
      atherosclerosis) and play opposing yet balancing roles; M2 macrophages have a
      delayed and progressive onset in the tumor microenvironment (concomitant with an
      immunosuppression of M1 macrophages). In this study, we show higher uptake of
      CPMV-AF488 and CPMV-PEG-AF488 by M2 macrophages compared to M1 macrophages. M1
      macrophages showed no uptake of CPMV-PEG-AF488. More specifically, M2 macrophages
      are known to be up-regulated in early atherosclerosis plaque. Indeed, previous
      work showed that M2 macrophages in plaque also correlate with CPMV
      internalization. These studies emphasize the potential effectiveness of CPMV as a
      tailored vehicle for targeting tumor macrophages involved in cancer metastasis or
      vascular inflammation and further highlight the potential of CPMV in targeted
      therapeutics against other diseases.

PMID- 22963599
TI  - Feasibility of using near-infrared spectroscopy for rapid quantification of
      17beta-estradiol sorption coefficients in soil.
AB  - Livestock manure contains natural steroid hormones, with the most potent being
      17beta-estradiol. The transport of steroid hormones from agricultural fields to
      adjacent water bodies can result in 17beta-estradiol environmental contamination
      impacting aquatic organisms. Sorption coefficients are useful input into models
      that estimate risk of water contamination. The feasibility of applying near
      infrared spectroscopy (NIRS) for determining sorption coefficients of 17beta
      estradiol in soil was investigated for two irregular undulating to hummocky
      terrain landscapes in Manitoba and Saskatchewan, Canada. A total of 609 soil
      samples in 140 soil profiles were collected from several horizons to a depth of 1
      m. Air-dried and sieved (2 mm) soil samples were analyzed for soil organic carbon
      (SOC), soil pH, and soil texture. Sorption coefficients of 17beta-estradiol were
      determined by a batch equilibrium process. Spectral data were collected from soil
      samples (25 g) using two instruments, the 45VISNIR Zeiss Corona (wavelength range
      700-1690 nm) and the Foss NIRSystems 6500 (wavelength range 1100-2500 nm).
      Regardless of the site and instrument, the predictive models were excellent for
      both SOC and 17beta-estradiol sorption coefficients. The data thus generated can
      be used as input parameters in fate models for efficient risk assessments and
      decision-making programs for environmental safety where soils are at risk of
      receiving inputs of 17beta-estradiol. Calibration results for soil pH were also
      adequate with Corona outperforming the Foss instrument. Soil texture predictions
      were relatively unsuccessful regardless of the instrument and site. 

PMID- 22963600
TI  - Structural basis for the enhanced stability of protein model compounds and
      peptide backbone unit in ammonium ionic liquids.
AB  - Protein folding/unfolding is a fascinating study in the presence of cosolvents,
      which protect/disrupt the native structure of protein, respectively. The
      structure and stability of proteins and their functional groups may be modulated
      by the addition of cosolvents. Ionic liquids (ILs) are finding a vast array of
      applications as novel cosolvents for a wide variety of biochemical processes that
      include protein folding. Here, the systematic and quantitative apparent transfer
      free energies (DeltaG'(tr)) of protein model compounds from water to ILs through
      solubility measurements as a function of IL concentration at 25  degrees C have
      been exploited to quantify and interpret biomolecular interactions between model
      compounds of glycine peptides (GPs) with ammonium based ILs. The investigated
      aqueous systems consist of zwitterionic glycine peptides: glycine (Gly),
      diglycine (Gly(2)), triglycine (Gly(3)), tetraglycine (Gly(4)), and cyclic
      glycylglycine (c(GG)) in the presence of six ILs such as diethylammonium acetate
      (DEAA), diethylammonium hydrogen sulfate (DEAS), triethylammonium acetate (TEAA),
      triethylammonium hydrogen sulfate (TEAS), triethylammonium dihydrogen phosphate
      (TEAP), and trimethylammonium acetate (TMAA). We have observed positive values of
      DeltaG'(tr) for GPs from water to ILs, indicating that interactions between ILs
      and GPs are unfavorable, which leads to stabilization of the structure of model
      protein compounds. Moreover, our experimental data DeltaG'(tr) is used to obtain
      transfer free energies (Deltag'(tr)) of the peptide backbone unit (or glycyl
      unit) (-CH(2)C?ONH-), which is the most numerous group in globular proteins, from
      water to IL solutions. To obtain the mechanism events of the ILs' role in
      enhancing the stability of the model compounds, we have further obtained m-values
      for GPs from solubility limits. These results explicitly elucidate that all alkyl
      ammonium ILs act as stabilizers for model compounds through the exclusion of ILs
      from model compounds of proteins and also reflect the effect of alkyl chain on
      the stability of protein model compounds.

PMID- 22963601
TI  - Oxybiotest project: microorganisms under pressure. Hyperbaric oxygen (HBO) and
      simple pressure interaction on selected bacteria.
AB  - BACKGROUND: HyperBaric Oxygen (HBO) therapy involves exposure to pure oxygen in
      a pressurized room, and it is an already well-established treatment for various
      conditions, including those originated by serious infections. Starting from the
      observation of an increased number of patients who were accessing our HBO units
      for diseases supported from concomitant multidrug-resistant microorganisms, as
      well as considering the evident clinical benefit and laboratory final outcome of
      those patients at the end of the treatment, aim of our study was to measure, or
      better define at least, if there was any interaction between a hyperbaric
      environment and some selected microorganisms and if those positive results were
      due to the increased oxygen partial pressure (pO2) value or just to the increased
      pressure, regardless of the fraction of inspired oxygen (FiO2) applied (21/100%).
      DESIGN AND METHODS: We applied various increased pO2 values in a hyperbaric
      environment. Our study design was tailored in four steps to answer four specific
      questions, ordered in a progressive process: OxyBioTest (OBT)-1,2,3, and 4.
      Specifically, we chose to investigate possible changes in the Minimum Inhibitory
      Concentration (MIC) and in the Minimum Bactericidal Concentration (MBC) of multi
      resistant microorganisms after a single session of hyperbaric therapy. RESULTS:
      OBT-1 and OBT-2 provide a semi-quantitative confirmation of the bacterio-cidal
      and cytostatic effects of HBO. HBO is cidal only if the total exposure pressure
      is elevated, and cidal or cytostatic effect are not always dependent on the pO2
      applied.OBT-4 has shown the adjuvant effect of HBO and antimicrobial drug against
      some selected bacteria. DISCUSSION: We seem allowed to hypothesize that only in
      case of a good approach to a lesion, permitting smaller bacterial loads thanks to
      surgical debridement and/or eventual antibiotic therapy for example, You can
      observe the clear effectiveness of the HyperBaric Oxygen (HBO) exposure as a
      valid adjuvant therapy, even when that lesion is substained from multidrug
      resistant micro-organisms. On the contrary when the bacterial load is very high
      we observe an unchanged situation or a just a slightly diminishing in the number
      of cfu/ml. CONCLUSIONS: Even if confined in this 'in vitro' environment and in a
      single treatment, just knowing the microorganism strain responsible of the lesion
      we seem allowed to both weight the possible related effectiveness using HBO
      Therapy (HBOT) and derive the best pO2 to treat the case. A further possible
      development of the study highlights a comparison between Acinetobacter baumannii
      (ACBA) and Pseudomonas aeruginosa (PSAE), and Escherichia coli (ESCO) and
      Klebsiella pneumoniae (KLPN).

PMID- 22963602
TI  - Utility of intraoperative frozen section during robot-assisted partial
      nephrectomy: a single institution experience.
AB  - BACKGROUND AND PURPOSE: Intraoperative frozen section (FS) analysis has been
      regarded as a paramount tool for immediate evaluation of tumor margin status
      during partial nephrectomy procedures. The aim of this study was to assess the
      utility of FS during robot-assisted partial nephrectomy (RAPN). PATIENTS AND
      METHODS: A retrospective review of our Institutional Review Board-approved
      prospectively maintained minimally invasive partial nephrectomy database yielded
      342 consecutive RAPN procedures from June 2007 to September 2011. Of these, the
      initial 128 cases underwent FS evaluation, whereas the following 214 cases did
      not. Patient demographics, perioperative outcomes, and final pathology results
      were analyzed and compared between the two groups. RESULTS: Body mass index,
      Charleson Comorbidity Index, tumor size, renal score, preoperative creatinine
      level, and estimated glomerular filtration rate (eGFR) were similar between both
      groups. Operative time was significantly longer in the no-FS group (193 vs 180
      min; P=0.04). Warm ischemia time (median 19 vs 19 min), estimated blood loss (150
      vs 200 mL), postoperative creatinine level (1.0 vs 1.1 mg/dL), and postoperative
      eGFR (75.6 vs 75.9) were similar between the no-FS group and FS group,
      respectively. Complications occurred in 32 (15.0%) and 31 (24.2%) cases in no-FS
      and FS, respectively (P=0.06). Final pathology results demonstrated seven cases
      of positive margins, 1 (1%), in the FS group and 6 (3%) in the no-FS group
      (P=0.19). Of the cases with positive margins at final pathology analysis, a
      R.E.N.A.L. score of 3/3 was found on closeness to renal sinus. Overall, three
      intraoperative positive margins were noted in the FS group (2.3%): One patient
      underwent radical nephrectomy and one reresection; one case was managed with
      observation only. CONCLUSION: Routine application of FS analysis during RAPN
      seems to provide a limited benefit. FS might be advisable for tumors with sinus
      invasion because they seem to carry a higher likelihood of positive surgical
      margin at final pathology determination.

PMID- 22963603
TI  - Beyond genetic tests and biomarkers: what about therapeutic misconception?

PMID- 22963604
TI  - A haplotype of the SMTN gene associated with myocardial infarction in Japanese
      women.
AB  - OBJECTIVES: Smoothelin is a specific kind of cytoskeletal protein present in
      smooth muscle cells. Some researchers have shown the relationship between
      smoothelin and atherosclerotic plaque. The human SMTN gene encodes smoothelin-A
      and smoothelin-B. The aim of the present study was to assess the association
      between the human SMTN gene and myocardial infarction (MI) using a haplotype
      based case-control study. METHODS: A total of 227 MI patients and 257
      supercontrols were genotyped for five single-nucleotide polymorphisms used as
      genetic markers of the human smoothelin gene. Data were analyzed for three
      separate groups: total subjects, men, and women. RESULTS: For the women, the
      frequency of the C-T-T-G haplotype (established by rs5997872, rs56095120,
      rs9621187, and rs10304) was significantly higher in the MI group than in the
      control group (p=0.012). CONCLUSIONS: We confirmed that the haplotype constructed
      using rs5997872, rs56095120, rs9621187, and rs10304 is a useful genetic marker of
      MI in Japanese females.

PMID- 22963606
TI  - No association of catechol-O-methyltransferase polymorphisms with schizophrenia
      in the Han Chinese population.
AB  - AIMS: Genetics play a major role in the etiology of schizophrenia (SZ). Catechol
      O-methyltransferase (COMT) is one of the promising candidate genes for SZ. A
      nonsynonymous single-nucleotide polymorphism (SNP), rs4680, causing a Valine
      (Val) to Methionine (Met) substitution, has been widely studied in relation to
      psychiatric phenotypes, including SZ, but with conflicting results. We conducted
      a two-stage study to examine the association of COMT polymorphisms with SZ in the
      Han Chinese population. RESULTS: Association analysis of nine SNPs in 768
      patients and 1348 controls failed to detect any positive markers or haplotypes.
      Then, we tested rs4680 in a validation sample of 963 patients and 992 controls,
      and no significant association was observed, but the cases significantly deviated
      from Hardy-Weinberg equilibrium (p=5.7e-4). There was no association of rs4680
      with SZ in the combined sample (n=4071, p=0.110, odds ratio=1.08). CONCLUSIONS:
      Our results do not support the association of COMT with SZ in the Han Chinese
      population.

PMID- 22963608
TI  - Vinyl azides derived from allenes: thermolysis leading to multisubstituted 1,4
      pyrazines and Mn(III)-catalyzed photochemical reaction leading to pyrroles.
AB  - Thermolysis of phosphorus-based vinyl azides under solvent- and catalyst-free
      conditions furnished a new route for 1,4-pyrazines. A simple one-pot, Mn(III)
      catalyzed photochemical route has been developed for multisubstituted pyrroles
      starting from allenes and 1,3-dicarbonyls via in situ-generated vinyl azides. The
      utility of new phosphorus-based pyrroles is also demonstrated in the Horner
      reaction. The structures of key products are unequivocally confirmed by X-ray
      crystallography.

PMID- 22963605
TI  - Single-nucleotide polymorphism at CYP27B1-1260, but not VDR Taq I, is possibly
      associated with persistent hepatitis B virus infection.
AB  - BACKGROUND: Vitamin D, beyond its role in calcium and bone metabolism, exhibits
      immunomodulatory effects on innate and adaptive immune pathways and is
      suggestively related to liver diseases. OBJECTIVE: This study investigated the
      association of single-nucleotide polymorphisms in genes involved in vitamin D
      functions with hepatitis B virus (HBV) infection. METHODS: Five hundred Chinese
      Han subjects, including 274 chronic HBV patients, 68 HBV infection resolvers, and
      158 healthy controls without HBV infection, were studied. The CYP27B1-1260
      promoter and the VDR Taq I polymorphisms were genotyped by polymerase chain
      reaction-restriction fragment length polymorphism. RESULTS: Although there was no
      difference between HBV patients and healthy controls, HBV patients and healthy
      controls had a higher frequency of the CYP27B1-1260 genotype CC (15.0% vs. 2.9%,
      p=0.004 and 13.3% vs. 2.9%, p=0.006, respectively) and allele C (38.3% vs. 25.7%,
      p=0.006 and 39.2% vs. 25.7%, p=0.006, respectively) compared with resolvers. The
      genotype and allele frequencies of the VDR Taq I polymorphism had no difference
      between patients, resolvers, and healthy controls. CONCLUSION: These results
      suggest that the CYP27B1-1260 promoter polymorphism is possibly associated with
      the persistence, but not susceptibility to HBV infection in Chinese HBV patients,
      and that the VDR Taq I polymorphism is not suggested to be related to chronic HBV
      infection.

PMID- 22963609
TI  - Synthesis of dumbbell-like ZnO microcrystals via a simple solution route.
AB  - Uniform dumbbell-like ZnO microcrystals had been successfully fabricated on a
      large scale via a facile solution technique under mild conditions. Obtained ZnO,
      with length of 1.2 to 1.6 MUm and diameters of 350 to 600 nm, exhibited well
      defined dumbbell-like morphology and hexagonal wurtzite structure and grew along
      the [001] direction. Effects of the reactant concentration on the sizes and
      morphologies of the ZnO products had been investigated, indicating that the
      reactant concentration played a crucial role in determining final sizes and
      shapes of the samples. In addition, the growth process of the dumbbell-like ZnO
      microcrystals was studied, and a possible formation mechanism was proposed.
      Furthermore, the optical properties of ZnO samples obtained at various reaction
      times were also investigated by photoluminescence (PL) spectroscopy. The PL
      spectra of the as-prepared dumbbell-like ZnO microcrystals showed a strong UV
      emission peak.

PMID- 22963610
TI  - Making an impact.
AB  - Cognitive Neuropsychiatry has secured recognition in Thomson's Science and Social
      Science Citation Indices which will lead to the calculation of the journal impact
      factor.

PMID- 22963611
TI  - The complete mitochondrial genome of the Spinetail Devilray, Mobula japanica.
AB  - The complete mitochondrial genome of a widely distributed pelagic ray, the
      Spinetail Devilray (Mobula japanica), consists of 18,880 bp with high A+T and low
      G content. Gene configuration and length is similar to other vertebrates and
      comprises 13 protein-coding genes, 2 rRNAs genes (12S and 16S rRNA), 22 tRNAs
      genes, and 1 major non-coding sequence, the control region. A remarkable feature
      in the mitochondrial genome of M. japanica is three tandemly repeated areas in
      the control region, together comprising a length of almost 1500 bp, making this
      to our knowledge the longest elasmobranch mitochondrial genome published so far.

PMID- 22963612
TI  - Barriers to the implementation of green chemistry in the United States.
AB  - This paper investigates the conditions under which firms are able to develop and
      implement innovations with sustainable development benefits. In particular, we
      examine "green chemistry" innovations in the United States. Via interviews with
      green chemistry leaders from industry, academia, nongovernmental institutions
      (NGOs), and government, we identified six major categories of challenges commonly
      confronted by innovators: (1) economic and financial, (2) regulatory, (3)
      technical, (4) organizational, (5) cultural, and (6) definition and metrics.
      Further analysis of these barriers shows that in the United States, two elements
      of these that are particular to the implementation of green chemistry innovations
      are the absence of clear definitions and metrics for use by researchers and
      decision makers, as well as the interdisciplinary demands of these innovations on
      researchers and management. Finally, we conclude with some of the strategies that
      have been successful thus far in overcoming these barriers, and the types of
      policies which could have positive impacts moving forward.

PMID- 22963613
TI  - Monothiol glutaredoxins function in storing and transporting [Fe2S2] clusters
      assembled on IscU scaffold proteins.
AB  - In the bacterial ISC system for iron-sulfur cluster assembly, IscU acts as a
      primary scaffold protein, and the molecular co-chaperones HscA and HscB
      specifically interact with IscU to facilitate ATP-driven cluster transfer. In
      this work, cluster transfer from Azotobacter vinelandii [Fe(2)S(2)](2+) cluster
      bound IscU to apo-Grx5, a general purpose monothiol glutaredoxin in A.
      vinelandii, was monitored by circular dichroism spectroscopy, in the absence and
      in the presence of HscA/HscB/Mg-ATP. The results indicate a 700-fold enhancement
      in the rate of [Fe(2)S(2)](2+) cluster transfer in the presence of the co
      chaperones and Mg-ATP, yielding a second-order rate constant of 20 000 M(-1) min(
      1) at 23  degrees C. Thus, HscA and HscB are required for efficient ATP-dependent
      [Fe(2)S(2)](2+) cluster transfer from IscU to Grx5. The results support a role
      for monothiol Grx's in storing and transporting [Fe(2)S(2)](2+) clusters
      assembled on IscU and illustrate the limitations of interpreting in vitro cluster
      transfer studies involving [Fe(2)S(2)]-IscU in the absence of the dedicated
      HscA/HscB co-chaperone system.

PMID- 22963614
TI  - EMTOX: Climate change impacts on natural toxins in marine and primary plant
      production system in north west Europe by 2040.

PMID- 22963615
TI  - Needle and syringe distribution trends in Western Australia, 1990 to 2009.
AB  - INTRODUCTION AND AIMS: To describe needle and syringe distribution trends of
      needle and syringe programs (NSP) between 1990 and 2009 in Western Australia, and
      explore contributing factors within the national and state strategic and
      legislative environment. DESIGN AND METHODS: The number of needles and syringes
      distributed by each of the four NSP types [needle and syringe exchange program
      (NSEP); health service; pharmacy; vending machine] between 1990 and 2009 were
      stratified by time period and geographic location using Microsoft Excel. RESULTS:
      Total needle and syringe distribution over the 20-year period increased by eight
      fold. Regional areas experienced the highest growth: 20-fold increase compared
      with seven-fold increase in metropolitan areas. The proportion of needles and
      syringes distributed through NSEPs increased from 33% to 62% between 1990 and
      2009, and through health services increased from 3% to 8% between 1994 and 2009.
      The proportion distributed through pharmacies decreased from 67% to 28% between
      1990 and 2009, and through vending machines from 7% to 1.3% between 1992 and
      2009. National and state HIV and hepatitis C strategies guided NSP provision at
      an early stage, and expedited legislative amendments to allow for the operation
      of approved NSPs. DISCUSSION AND CONCLUSIONS: The majority of growth occurred
      through the NSEPs and health service NSPs, which are publicly funded NSPs and
      provide injecting equipment either on 'exchange' or free-of-charge respectively.
      The Health Department of Western Australia recognises the increasing reliance on
      publicly funded NSPs and the need to continue this cost-effective public health
      program.

PMID- 22963616
TI  - Developing the Autism Model of Implementation for autism spectrum disorder
      community providers: study protocol.
AB  - BACKGROUND: Currently, 1 out of 88 children are diagnosed with an autism spectrum
      disorder (ASD), and the estimated cost for treatment services is $126 billion
      annually. Typically, ASD community providers (ASD-CPs) provide services to
      children with any severity of ASD symptoms using a combination of various
      treatment paradigms, some with an evidence-base and some without. When evidence
      based practices (EBPs) are successfully implemented by ASD-CPs, they can result
      in positive outcomes. Despite this promise, EBPs are often implemented
      unsuccessfully and other treatments used by ASD-CPs lack supportive evidence,
      especially for school-age children with ASD. While it is not well understood why
      ASD-CPs are not implementing EBPs, organizational and individual characteristics
      likely play a role. As a response to this need and to improve the lives of
      children with ASD and their families, this study aims to develop and test the
      feasibility and acceptability of the Autism Model of Implementation (AMI) to
      support the implementation of EBPs by ASD-CPs. METHODS/DESIGN: An academic
      community collaboration developed to partner with ASD-CPs will facilitate the
      development of the AMI, a process specifically for use by ASD community-based
      agencies. Using a mixed methods approach, the project will assess agency and
      individual factors likely to facilitate or hinder implementing EBPs in this
      context; develop the AMI to address identified barriers and facilitators; and
      pilot test the AMI to examine its feasibility and acceptability using a specific
      EBP to treat anxiety disorders in school-age children with ASD. DISCUSSION: The
      AMI will represent a data-informed approach to facilitate implementation of EBPs
      by ASD-CPs by providing an implementation model specifically developed for this
      context. This study is designed to address the real-world implications of EBP
      implementation in ASD community-based agencies. In doing so, the AMI will help to
      provide children with ASD the best and most effective services in their own
      community. Moreover, the proposed study will positively impact the field of
      implementation science by providing an empirically supported and tested model of
      implementation to facilitate the identification, adoption, and use of EBPs.

PMID- 22963617
TI  - Comparison of the effect of different techniques for measurement of Ki67
      proliferation on reproducibility and prognosis prediction accuracy in breast
      cancer.
AB  - AIMS: The proliferation factor Ki67 is prognostic in breast cancer and included
      in international therapy guidelines, but measurement procedures differ between
      laboratories. We compared the reproducibility and prognostic value of different
      Ki67 sampling and measurement methods. METHODS AND RESULTS: In 237 T(1,2) N(0)
      M(0) breast cancers without adjuvant systemic treatment, strictly standardized
      section thickness, automated antigen retrieval and immunohistochemistry were
      used. The percentages of Ki67-positive nuclei were assessed using (i) a 'quick
      scan rapid estimate', (ii) ocular-square-guided counts by independent
      pathologists, (iii) computerized point-grid-sampling interactive morphometry
      (CIM) and (iv) automated digital image analysis (DIA). Quick-scan rapid estimates
      were poorly reproducible. The optimal prognostic thresholds of Ki67 counts by two
      pathologists differed greatly (4%, 14%; kappa: 0.36), with many therapeutic
      differences. CIM-Ki67 and DIA-Ki67 were strongly prognostic (P<0.0001) and
      reproducible. DIA-Ki67 (threshold: 6.5%) was the strongest and most robust
      prognosticator (the threshold could vary from 4 to 15% without significant
      prognostic loss). Ki67 was prognostically strongest in the periphery of the
      tumour. CONCLUSION: In node-negative breast cancer without adjuvant systemic
      treatment, Ki67% by DIA, but not subjective counts, is reproducible and
      prognostically strong. This casts serious doubt on therapeutic guidelines using
      subjective counts of Ki67.

PMID- 22963619
TI  - A comparative study of two novel nanosized radiolabeled analogues of methionine
      for SPECT tumor imaging.
AB  - It has been reported that most tumor cells show an increased uptake of variety of
      amino acids specially methionine when compared with normal cells and amino acid
      transport is generally increased in malignant transformation. Based on the
      evidences, two novel nanosized analogues of methionine (Anionic Linear Globular
      Dendrimer G(2), a biodigredabale anionic linear globular-Methionin, and DTPA
      Methionine(1) conjugates) were synthesized and labeled with (99m)Tc and used in
      tumor imaging/ therapy in vitro and in vivo. The results showed marked tumor
      SPECT molecular imaging liabilities for both compounds but with a better
      performance by administration of (99m)Tc-Dendrimer G(2)-Methionin. The results
      also showed a good anticancer activity for 99mTc-DTPA-Methionine. Based on the
      present study (99m)Tc-Dendrimer G(2)-Methionin or 99mTc-DTPA-(Methionine)(1) have
      potentials to be used in tumor molecular imaging as well as cancer therapy in
      future.

PMID- 22963620
TI  - New clinical perspectives of hypolipidemic drug therapy in severe
      hypercholesterolemia.
AB  - Patients with homozygous familial hypercholesterolemia (HoFH) represent the most
      severe patients within the spectrum of dyslipidemias. Untreated Low-Density
      Lipoprotein Cholesterol (LDL-C) levels in these patients are usually in the range
      500 to 1200 mg/dL. Moreover, these patients exhibit a scarce responsiveness or
      even non responsiveness to oral lipid lowering agents. Patients with heterozygous
      familial hypercholesterolemia (HetFH) tend to have untreated LDL-C levels of 250
      500 mg/dL. Many of these patients are responsive to 3-hydroxy-3-methylglutaryl
      coenzyme A (HMGCoA-reductase) inhibitors (statins) and/or other specific drugs.
      Unfortunately, a significant subset of these patients (5-10%) have a severe
      and/or refractory form of HetFH and after current maximal oral therapy, they
      remain significantly far from treatment goals (The National Cholesterol Education
      Program (NCEP) ATPIII guidelines). This would be defined as LDL-C levels of >=
      190 mg/dL - prior Coronary Heart Disease (CHD) or CHD equivalent - or >= 250
      mg/dL (no prior CHD or CHD risk-equivalent). The only current therapy option for
      these patients is Low Density Lipoprotein-apheresis (LDL_a). While LDL_a is very
      effective in reducing LDL-C, many patients do not receive this extracorporeal
      therapy because of costs and limited availability of LDL_a centers. Recently, new
      potent lipid-lowering drugs have been developed and are currently under
      investigation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a
      critical role controlling the levels of LDL-C. Studies have demonstrated that
      PCSK9 acts mainly by enhancing degradation of the Low-Density Lipoprotein
      receptor (LDLR) protein in the liver. Inactivation of PCSK9 in mice reduces
      plasma cholesterol levels. Since the loss of a functional PCSK9 in human is not
      associated with apparent deleterious effects, this protease is becoming an
      attractive target for lowering plasma LDL-C levels either alone or in combination
      with statins. Mipomersen, an apolipoprotein B (ApoB) synthesis inhibitor, for
      lowering of LDL-C showed to be an effective therapy to reduce LDL-C
      concentrations in patients with HoFH who are already receiving lipid-lowering
      drugs, including high-dose statins. Lomitapide is a potent inhibitor of
      microsomal triglyceride transfer protein and is highly efficacious in reducing
      LDL-C and triglycerides (TG). Lomitapide is currently being developed for
      patients with HoFH at doses up to 60 mg/d. These new powerful lipid-lowering
      drugs might be possibly superior than available hypolipidemic agents. Their
      mechanisms of action, effectiveness, safety, and indication in severe,
      genetically determined dyslipidemias, are reviewed.

PMID- 22963618
TI  - Olive phenolic compounds: metabolic and transcriptional profiling during fruit
      development.
AB  - BACKGROUND: Olive (Olea europaea L.) fruits contain numerous secondary
      metabolites, primarily phenolics, terpenes and sterols, some of which are
      particularly interesting for their nutraceutical properties. This study will
      attempt to provide further insight into the profile of olive phenolic compounds
      during fruit development and to identify the major genetic determinants of
      phenolic metabolism. RESULTS: The concentration of the major phenolic compounds,
      such as oleuropein, demethyloleuropein, 3-4 DHPEA-EDA, ligstroside, tyrosol,
      hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits
      of 12 olive cultivars. The content of these compounds varied significantly among
      the cultivars and decreased during fruit development and maturation, with some
      compounds showing specificity for certain cultivars. Thirty-five olive
      transcripts homologous to genes involved in the pathways of the main secondary
      metabolites were identified from the massive sequencing data of the olive fruit
      transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using
      RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and
      Dolce d'Andria, respectively) during three different fruit developmental stages.
      A strong correlation was observed between phenolic compound concentrations and
      transcripts putatively involved in their biosynthesis, suggesting a
      transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H
      and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase,
      geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost
      exclusively present at 45 days after flowering (DAF), suggesting that these
      compounds might play a key role in regulating secoiridoid accumulation during
      fruit development. CONCLUSIONS: Metabolic and transcriptional profiling led to
      the identification of some major players putatively involved in biosynthesis of
      secondary compounds in the olive tree. Our data represent the first step towards
      the functional characterisation of important genes for the determination of olive
      fruit quality.

PMID- 22963621
TI  - Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with
      lactosylnorcantharidin phospholipid complex: preparation, characterization, and
      therapeutic evaluation in vivo and in vitro.
AB  - Liposomes loaded with lactosyl-norcantharidin phospholipid complex (LPC) were
      prepared, in which soybean phosphatidylcholine was used to improve the
      liposolubility of lactosyl-norcantharidin (Lac-NCTD). The pH-sensitive LPC
      liposomes (pH-LPC-lips) were obtained by electrostatic adsorption of the
      carboxymethyl chitosan onto the surface of the liposomes. The in vitro drug
      release of pH-LPC-lips and LPC-lips was investigated in dissolution media with pH
      ranging from 1.0 to 8.0. The in vitro antitumor activity and cellular uptake of
      Lac-NCTD and its liposomes to HepG2 cells were studied. The pH-LPC-lips
      demonstrated strong cytotoxicity against the cells and easily permeated the cell
      membrane. The in vivo antitumor activities of Lac-NCTD and its liposomes were
      evaluated in mice bearing H22 liver tumors. The pH-LPC-lips displayed the best
      tumor inhibitory effect. The optical imaging results indicated that Cy7- labeled
      pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice.
      Therefore, pH-LPC-lips can be regarded as liver-targeting agents that combine
      targeting and active releasing.

PMID- 22963622
TI  - The role of a disturbed arginine/NO metabolism in the onset of cancer cachexia: a
      working hypothesis.
AB  - Cancer cachexia is a complex catabolic state in patients with a malignancy,
      associated with increased morbidity and mortality. This syndrome is characterized
      by a redistribution of the body's protein content and a subsequent muscle
      wasting. The aetiology of this syndrome seems multifactorial, but remains
      unclear. It is suggested that this catabolic state occurs in response to the
      alterations in immune interactions between tumor and host. The amino acid
      arginine and its derivate nitric oxide (NO) play various roles in anti-tumor
      immune response and the body's homeostasis. Glutamine is the precursor for
      arginine de novo synthesis and the most abundant amino acid in the body, mainly
      stored in skeletal muscle. Tumors develop a protection mechanism against the
      specific anti-tumor attack of the immune system by recruiting myeloid derived
      suppressor cells (MDSC). The MDSC deplete arginine levels and disturb NO
      production. We here hypothesize that the perturbation of the arginine/NO
      metabolism plays a significant role in the aetiology of cancer cachexia.
      Arginine/ NO metabolism is disturbed in patients with cancer. The body will try
      to correct this perturbation by mobilizing arginine and glutamine from muscles.
      The decreased arginine levels and the disturbed NO production activate several
      cascades, which in turn inhibit protein synthesis and promote proteolysis,
      leading to cachexia. Cachexia remains one of the most frequent and damaging
      opportunistic syndromes in cancer patients. In this review we will elaborate on a
      new hypothesised concept and the underlying mechanisms of this syndrome. New
      studies are essential to ground this hypothesis and to develop interventions to
      break through the pathological mechanisms underlying cachexia.

PMID- 22963623
TI  - Terpene compounds in nature: a review of their potential antioxidant activity.
AB  - Reactive Oxygen Species are involved in the pathological development of many
      important human diseases such as neurodegenerative diseases, cardiovascular
      processes, diabetes and many others. The most promising strategy to prevent from
      the oxidative damage caused by these reactive species is the use of antioxidant
      molecules. These compounds can act as direct antioxidants through free radical
      scavenging mechanisms and/or as indirect antioxidants by enhancing the
      antioxidant status (enzymatic and non-enzymatic). Terpenes, one of the most
      extensive and varied structural compounds occurring in nature, display a wide
      range of biological and pharmacological activities. Here we highlight their
      antioxidant properties. Due to their antioxidant behaviour terpenes have been
      shown to provide relevant protection under oxidative stress conditions in
      different diseases including liver, renal, neurodegenerative and cardiovascular
      diseases, cancer, diabetes as well as in ageing processes. Evidence for this
      comes from the increasing number of publications on this issue in recent years.
      This review provides a complete overview of the natural terpenes with potential
      antioxidant properties, focusing on their source, structures, antioxidant
      mechanisms through which they exert their pharmacological and possible
      therapeutic activities.

PMID- 22963624
TI  - 4'-Aminochalcones as novel inhibitors of the chlorinating activity of
      myeloperoxidase.
AB  - The excessive activation of neutrophils generates reactive oxygen species (ROS)
      and the secretion of primary granular enzymes, such as myeloperoxidase (MPO),
      which is implicated in numerous inflammatory diseases. The aim of this study was
      to evaluate chalcones as inhibitors of the chlorinating activity of MPO using in
      vitro and ex vivo assays. In addition to cytotoxic properties, the inhibition of
      respiratory burst, the scavenger capacity, and the oxidation potential were
      measured. 4'-Aminochalcone (1), 4'-amino-4- fluorochalcone (2), and 4'-amino-4
      methylchalcone (3) exhibited potent inhibition of the chlorinating activity of
      MPO, as evaluated in a neutrophil system and a free cell system, to the following
      degree: (1) IC50 = 0.265 ? 0.036 MUmol L-1; (2) IC50 = 0.250 ? 0.081 MUmol L-1;
      and (3) IC50 = 0.250 ? 0.012 MUmol L-1. These values were similar to those for 5
      fluorotryptamine (IC50 = 0.192 ? 0.012 MUmol L-1), a compound considered to be a
      potent MPO inhibitor. These aminochalcones were not toxic to neutrophils at
      concentrations below 100 MUmol L- 1, as determined by the trypan blue exclusion
      assay. Compounds 1-3 presented a high oxidation potential (Epa1 ? 0.80 V), low
      scavenger capacity against DPPH* and HOCl, and low inhibition of respiratory
      burst. These data indicated that aminochalcones are potent inhibitors of MPO
      chlorinating activity, a new property for chalcone derivatives, given that they
      are neither antioxidant agents nor inhibitors of respiratory burst. In
      conclusion, the selected aminochalcones have potential as pharmacological agents
      for inflammatory diseases.

PMID- 22963625
TI  - Dendrimers in photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a promising approach to treat certain types of
      cancer. PDT was proposed as a useful oncology tool more than 30 years ago but it
      has limitations. The success of PDT depends predominantly on photosensitizers and
      development of an effective second generation is continuing. Dendrimers possess
      architecture suitable for incorporating specific functional moieties and are a
      promising venue for further investigations. This review describes the use of
      dendrimers in PDT and how they can aid in overcoming obstacles encountered during
      PDT.

PMID- 22963626
TI  - From metallodrugs to metallodendrimers for nanotherapy in oncology: a concise
      overview.
AB  - Metallodrugs (organometallic complexes) bearing at least one metal-carbon bond -
      represent original and powerful tools for diverse therapeutic applications based
      on the development of "bioorganometallic chemistry". To date, various
      metallodrugs were described with very interesting biological activities as
      antimalarials, antibacterials, neuroprotectors, against arthritis, for
      chemotherapy etc. Anticancer Pt-based drugs are the main complexes used in the
      treatment of several cancers, but unfortunately these complexes show elicit and
      severe toxicities and resistance effects. The remarkably unique and tunable
      properties of dendrimers have made them promising tools for diverse biomedical
      applications such as diagnostics, gene therapy and drug delivery including in
      oncology. Recent studies have shown that well designed dendritic carriers
      overcome such as poor solubility, permeability, biocompatibility, bioavailability
      and toxicity of the native drug. This review reports on the recent advances for
      the use of metallodrugs and dendritic based carriers (drug-dendrimer conjugates
      and drug encapsulation) in oncology. Advantages, limitations and opportunities in
      oncology of such materials are discussed and compared.

PMID- 22963627
TI  - In vitro studies of water-stable cationic carbosilane dendrimers as delivery
      vehicles for gene therapy against HIV and hepatocarcinoma.
AB  - Here we present a synthetic procedure for water-stable carbosilane dendrimers
      containing ammonium groups at the periphery of type Gn
      {[Si(CH2)3N+(Me)(Et)CH2CH2N+Me3]x (CF3SO3 -)y} which have been used as non-viral
      vectors for transfecting different types of nucleic acids against two different
      medical problems, HIV and hepatocarcinoma. These systems have shown to be non
      toxic in both PBMC and HepG2 cell lines under the experimental conditions and are
      able to form nanoconjugates with nucleic acids perfectly stable over time and in
      a wide range of pH values, which leads to the conclusion that the interaction
      between dendrimer and nucleic acid is very strong. In addition, a high degree of
      transfection using these nanoconjugates has been observed, ranging from 70-90%
      depending on the generation and in the particular case of PBMC transfection with
      anti-HIV oligonucleotides. However, besides of the good properties shown by the
      dendrimers here prepared as transfecting agents, only moderate effect was
      observed in functional experiments for hepatocarcinoma, as a result of the strong
      interaction between dendrimer and nucleic acid. Nevertheless, it is important to
      mention that an IRS-4 knock-down of 40% in HepG2 achieves an analogous degree of
      cell sensitization to cancer treatment, which may represent a major advance in
      the hepatocarcinoma treatment when appropriate dendrimers as transfection agents
      are used.

PMID- 22963628
TI  - Dendrimer-modified solid supports: nanostructured materials with potential drug
      allergy diagnostic applications.
AB  - Complex functional materials consisting of bioactive molecules immobilized on
      solid supports present potential applications in biosensoring. Advances in the
      fabrication of these surface materials are of growing interest for antibody-based
      diagnosis. This work exploits dendrimers as versatile nanostructures for
      templating sensor surfaces and the critical role of the immobilization protocol
      in the solid supports cellulose and zeolites, of organic and inorganic
      composition respectively. The fabrication and characterization, including the
      degree of functionalization and reproducibility, of different nanostructured
      materials are described. To validate the approach, the fabricated supports were
      further used as a solid phase for developing a radioimmunoassay to detect
      immunoglobulin E (IgE) specific to penicillin, the antibody involved in immediate
      allergy responses to this drug. The dendrimer-modified supports provide assays
      with significantly enhanced sensitivity, as well as increase the availability of
      biomolecules for specific interaction and minimize nonspecific adsorptions
      through appropriate functionalization protocols in each case. The manufacturing
      methodology involved the use of a long, flexible hydrophilic spacer in the
      cellulose materials, and a higher surface density of the immobilized dendrimers
      in the zeolite crystals. The ability of hybrid zeolite materials in such
      biosensing applications was evaluated for the first time. The assays were
      validated in human serum samples from patients allergic to penicillin and from
      non-allergic controls. The specificity and improved sensitivity of the dendrimer-
      modified supports make these strategies versatile for different bioactive
      molecules and could have significant implications for the quantification of a
      wide range of specific IgE antibodies and other biomolecules of diagnostic
      interest.

PMID- 22963629
TI  - Dendrimers and the development of new complex nanomaterials for biomedical
      applications.
AB  - New nano-scale drug carriers offer the possibility of increasing the therapeutic
      index of drug molecules by increasing their effectiveness, diminishing their
      toxicity against physiological tissues and achieving controlled therapeutic
      levels for a prolonged time. This review gives an overview of approaches to the
      development of these novel complex nanocarriers with emphasis on those involving
      dendrimers and related systems. The combination of two of more nano-sized units
      for producing an overall system with unique properties could be advantageous
      compared to more simple nanotechnology-based carriers. Recent advances in
      medicinal chemistry offer the possibility of exact tailoring of the properties of
      such complex systems which, in conjunction with full physicochemical
      characterization, may lead to novel and highly effective drug products. An
      assessment is given of the potential of systems such as chimeric advanced Drug
      Delivery nano Systems (chi-aDDnSs) for the delivery of drugs compared with
      conventional carriers. Rational synthesis of molecules that can act as modulators
      of the properties of chi-aDDnSs and may be the future in the design and
      development of nanocarriers, not only for the delivery of drug molecules but also
      for genetic material and imaging agents is sought.

PMID- 22963630
TI  - The seemingly trivial yet challenging synthesis of poly(aminoester) dendrimers.
AB  - Poly(aminoester) dendrimers are expected to hold great promise as biodegradable
      nanocarriers for drug delivery due to their advantageous properties allowing
      their biodegradability, potentially lower toxicity and possibility of diverse
      chemical conjugations. The synthetic strategies for constructing such dendrimers
      include the amine branching method, the ester formation method, the combination
      of both methods as well as the recently emerging click chemistry based synthesis.
      We present here an overview on the current state of synthesizing poly(aminoester)
      dendrimers and discuss the benefits and limitations of each strategy with a view
      to stimulating a fueled interest in the development of efficient and reliable
      methodologies to synthesize such dendrimers.

PMID- 22963631
TI  - Antiviral properties against HIV of water soluble copper carbosilane dendrimers
      and their EPR characterization.
AB  - We describe here the use of anionic carbosilane dendrimers to obtain new copper
      complexes. UV-Vis and a computer aided analysis of the EPR spectra provided
      information about the coordination modes of copper depending on the nature of the
      dendrimer and about the geometry and structure of the complexes in solution. Some
      of these metallo-dendrimers have been tested "in vitro" as antiviral compounds in
      the inhibition of HIV infection in pre and post-infection treatment.

PMID- 22963632
TI  - Fluorescent dendrimers as sensors for biologically important metal cations.
AB  - The review presents fluorescence spectroscopic studies on the capacities of newly
      synthesized polypropyleneamine and polyamidoamine fluorescent dendrimers to
      detect biologically important metal ions. It has been shown that those
      fluorescent dendrimers whose periphery comprises 1,8-napthalimide fragments are
      highly sensitive to metal ions which are of great importance to the living
      organisms.

PMID- 22963633
TI  - The effect of PAMAM dendrimers on mesenchymal stem cell viability and
      differentiation.
AB  - Stem cells and nanomaterials are two new and exciting fields of science that are
      evolving very fast and that are starting to establish ties. Nanomaterials should,
      however, be designed to interact with stem cells without compromising their
      biological characteristics, in other words, without affecting their viability and
      differentiation potential. In the present report and for the first time, the
      effects of poly(amidoamine) (PAMAM) dendrimers on the viability and
      differentiation ability towards the osteogenic and adipogenic lineages of human
      mesenchymal stem cells (hMSCs) are systematically evaluated. Studies were done as
      a function of the cell culture media composition and PAMAM dendrimer surface
      functionalization, generation, and concentration. hMSCs were exposed to amino and
      hydroxyl (generations 2, 4 and 6), and carboxylate (generations 1.5, 3.5 and 5.5)
      functionalized dendrimers, at two different concentrations (10 MUg/mL and 0.5
      MUg/mL), for a period of 21 days. Overall, the results revealed that amino
      functionalized dendrimers can be severely cytotoxic, the extension of cell death
      being dependent on the concentration of amino groups in solution. However, in all
      cases, the differentiation of hMSCs towards the osteogenic and adipogenic
      phenotypes seems not to be affected as demonstrated by staining in in vitro
      cultures.

PMID- 22963634
TI  - Block copolymers for drug delivery nano systems (DDnSs).
AB  - The application of polymers in medicine, as components of drug carriers, as well
      as their synthetic strategies are considered essential for producing and
      developing new drug formulations against human deceases. The synthesis of block
      copolymers is a timeconsuming process with a high cost of the final product,
      although several block copolymer systems have been already commercialized
      successfully. The biocompatibility, the biodegradability and the non toxic
      profile of newly synthesized polymers towards healthy tissues, should be taken
      into account in order to be acceptable for biomedical applications. In this
      review article, focus is placed on new approaches and synthetic strategies for
      preparing novel block copolymers and their utilization as parts of new and
      advanced Drug Delivery nanoSystems (aDDnSs) with a Modulatory Controlled Release
      profile (MCR). Such complex and advanced nanosystems can alter the
      pharmacokinetic properties of the encapsulated drug and consequently its
      effectiveness. Emphasis is given to the use of living polymerization
      methodologies and post polymerization chemical transformation reactions for the
      synthesis of mainly diblock copolymers for novel drug delivery nanosystems.
      Issues related to self-assembly of block copolymers in solution toward formation
      of colloidal functional nanostructures that can serve as nanocontainers and
      nanocarriers, and strategies for controlling encapsulation of specific drugs are
      also discussed. Specific examples are reported mainly on diblock copolymer
      systems, including authors' recent work.

PMID- 22963635
TI  - Tell me something I do not know. Multiscale molecular modeling of dendrimer/
      dendron organization and self-assembly in gene therapy.
AB  - Due to the relative easy synthesis and commercial availability, nanovectors based
      on dendrimers and dendrons are among the most utilized non-viral vectors for gene
      transfer. Contextually, recent advances in molecular simulations and computer
      architectures not only allow for accurate predictions of many structural,
      energetical, and eventual self-assembly features of these nanocarriers per se,
      but are able to yield vital (and perhaps otherwise unattainable) molecular
      information about the interactions of these nanovectors with their nucleic acid
      cargoes. In the present work, we aim at reviewing our own efforts in the field of
      multiscale molecular modeling of these interesting materials. In particular, our
      originally developed computational recipes will be presented, and the link
      between simulations and experiments will be described and discussed in detail.
      This review is written by computational scientists for experimental scientists,
      with the specific purpose of illustrating the potentiality of these methodologies
      and the usefulness of multiscale molecular modeling as an innovative and
      complementary tool in their current research.

PMID- 22963636
TI  - Validation of a generation 4 phosphorus-containing polycationic dendrimer for
      gene delivery against HIV-1.
AB  - Gene therapy, in which oligomeric genetic material is carried into cells by nano
      sized gene delivery vehicles to interfere with gene expression, represents a
      promising approach for preventive therapy against HIV/AIDS pandemic. Herein, we
      evaluate the usefulness of a phosphorus-containing dendrimer G4(NH+Et2Cl-)96 as a
      delivery agent of ODNs and siRNAs. G4(NH+Et2Cl-)96 formed stable complexes with
      ODNs or siRNAs and exhibited very low cytotoxicity in Sup T1 cells or PBMC.
      Functional validation was performed by using specific siRNA against HIV-1 Nef,
      siNEF to interfere in HIV-1 replication. G4(NH+Et2Cl-)96/siNEF dendriplex showed
      a high efficiency in Nef silencing. Furthermore, in vitro treatment of HIV
      infected PBMC with G4(NH+Et2Cl-)96/siNEF dendriplex significantly reduced the
      viral replication. Our results prove the usefulness of phosphorus-containing
      dendrimers to deliver and transfect siRNA into CD4-T cells as a potential
      alternative therapy in the HIV-1 infection.

PMID- 22963637
TI  - Functional nanogels for biomedical applications.
AB  - This review addresses current and future perspectives of nanogel technology for
      nanomedicine. The synthetic methodologies and material properties of nanogels
      prepared by chemical meanings are discussed in detail, and examples that
      illustrate the different methodologies are presented. Applications in the fields
      of drug and gene delivery, smart imaging modalities, responsive materials, and
      multivalency as a therapeutic approach highlight the enormous potential of the
      functional nanogels as novel polymeric platforms for biomedicine.

PMID- 22963638
TI  - Dendrimers as vectors for genetic material delivery to the nervous system.
AB  - Transfection of genetic material into primary neuronal cultures remains a
      challenge because of the intrinsic difficulty in transfecting this type of cell.
      This review covers the recent developments in the use of dendrimers for siRNA and
      DNA transfection in both neuronal and glial cells. Crossing the blood brain
      barrier crossing represents a challenge for the effective use of dendrimer
      mediated delivery of therapeutic agents to the central nervous system. We will
      discuss the effectiveness, both in vitro and in vivo, of various dendrimers in
      delivering genetic material to neural tissue and its ability to cross the blood
      brain barrier. In addition, the use of dendrimers as a potential new therapy in
      the treatment of glioblastoma will be presented.

PMID- 22963639
TI  - Dendrimers in therapy for breast and colorectal cancer.
AB  - Current trends in research dealing with methods of developing effective
      chemotherapy for the two most dangerous killers - breast and colon cancers have
      been discussed. The input brought by nanotechnology is presented with particular
      stress on the use of dendrimers. These unique "polymeric compounds" after
      modification can form intelligent species, transporting drugs into specific areas
      and at the same time can be used for monitoring the state of organs attacked by
      cancer cells, as well as the progress of the curing process. They can help to
      limit the anticancer drugs delivery to designed goals only, eliminating many side
      effects of chemotherapy. Breast and colon cancer are major problem for public
      health care in many countries all over the world. During last twenty years a
      dramatic increase in incidence of both of them has been observed, especially in
      industrialized countries. Probably, both of them are caused, apart from the
      hereditary syndromes, by specific point mutation, some hormonal factors in breast
      cancer and by the strong co-influence of environmental factors and dietary
      exposure of a patient.

PMID- 22963640
TI  - Role of generation, architecture, pH and ionic strength on successful siRNA
      delivery and transfection by hybrid PPV-PAMAM dendrimers.
AB  - Small interfering RNA (siRNA) constitutes an excellent way of knocking down
      genes. However, it requires the use of delivery systems to reach the target
      cells, especially to neuronal cells. Dendrimers are one of the most widely used
      synthetic nanocarriers for siRNA delivery. However, due to the complexity of the
      dendrimer-siRNA interactions, when a new dendritic carrier is designed it is
      difficult to predict its efficiency to bind and to deliver siRNA. At the same
      time it is not easy to understand the origin of eventual limited functionalities.
      We have modeled the interactions between two dendrimers (TDG-G1 and TDG-G2) and
      siRNA using molecular dynamics (MD) simulation. The results were compared to
      experimental physico-chemical parameters such as siRNA complexation, complex
      stability, size, and zeta potentials and biological effects such as down
      regulation of a specific RNA expression in cortical neurons in culture. Data
      indicate that the combination of rigid core and flexible branches guarantees
      strong siRNA binding, which is important to have a good transfection profile.
      However, the successful nanocarrier for siRNA delivery (TDG-G1) is identified not
      only by a high affinity for siRNA, but by a favorable equilibrium between a
      strong binding and the ability to release siRNA to exert its biological action.
      The conditions under which the dendriplex is formed are also relevant for
      transfection efficiency and biological activity.

PMID- 22963641
TI  - Apparent low-level HIV RNA viraemia related to sample processing time.

PMID- 22963642
TI  - Rapidly increasing incidence of eosinophilic esophagitis in a large cohort.
AB  - BACKGROUND: Recent literature has shown increasing incidence and prevalence rates
      of eosinophilic esophagitis (EoE). However, data are mainly based on small
      studies and come from centers dedicated to EoE. Aim of this study was to estimate
      the incidence rates of EoE by using a large database. METHODS: We performed a
      cross-sectional study of the pathology reports describing esophageal eosinophilia
      from 1996 through 2010, using the nationwide network and registry of histo- and
      cytopathology in The Netherlands (PALGA). All histopathology reports nationwide
      enter this database. We classified cases according to the diagnosis made by the
      pathologist. Annual incidence rates of EoE were estimated. KEY RESULTS: Our
      search criteria yielded 8838 positive pathology reports. Eosinophilic esophagitis
      was diagnosed in 674 patients, of which 74% were men. In another 174 patients, no
      distinction was made between eosinophilia caused by gastro-esophageal reflux
      disease or EoE. The incidence of EoE increased considerably over the years, being
      0.01 in 1996, 0.01 in 2000, 0.14 in 2005, and 1.31 per 100,000 persons in 2010.
      Eosinophilic esophagitis was diagnosed in all age groups, but in 2010 the highest
      incidence was seen in 20-29 years old males, in whom it was estimated to be 3.23
      per 100,000 persons. The incidence in children was 0.73 per 100,000 in 2010. No
      seasonal variation in diagnosis of EoE was observed. CONCLUSIONS & INFERENCES: In
      this large study, we found robust data on increasing incidence rates of pediatric
      and adult EoE in the past 15 years. This rapidly increasing incidence has not
      reached a plateau yet.

PMID- 22963643
TI  - Exploring laypeople's epistemic beliefs about medicine - a factor-analytic survey
      study.
AB  - BACKGROUND: The aim of this study was to develop an instrument to measure
      laypeople's beliefs about the nature of medical knowledge and knowing (the EBAM).
      Such beliefs should be a target of increased research interest because they
      influence how people handle medical information, for example in shared decision
      making. METHODS: An online survey was completed by 284 participants. Items
      assessed different aspects of laypeople's epistemic beliefs about medicine and
      explicitly focused on the appearance of medical knowledge in everyday life and
      the evaluation of different sources as a way to justify knowledge. RESULTS:
      Factor analysis yielded a five-factor solution for the instrument. Dimensions
      covered by the instrument are certainty of medical knowledge, credibility of
      medical textbooks, credibility of medical information on the Internet,
      justification of medical knowledge, and preliminarity of medical knowledge.
      CONCLUSIONS: Results indicate that laypeople have meaningful beliefs about the
      nature of medical knowledge and the trustworthiness of different sources. The
      instrument developed seems promising for measuring laypeople's epistemic beliefs
      about medicine, which may help to increase patients' compliance in medical
      decision making.

PMID- 22963646
TI  - Surface tension of binary mixtures of 1-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ionic liquids: experimental measurements and
      soft-SAFT modeling.
AB  - Ionic liquids have attracted a large amount of interest in the past few years.
      One approach to better understand their peculiar nature and characteristics is
      through the analysis of their surface properties. Some research has provided
      novel information on the organization of pure ionic liquids at the vapor-liquid
      interface; yet, a systematic study on the surface properties of mixtures of ionic
      liquids and their organization at the surface has not previously been carried out
      in the literature. This work reports, for the first time, a comprehensive
      analysis of the surface organization of mixtures of ionic liquids constituted by
      1-alkyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquids,
      [C(n)mim][NTf(2)]. The surface tension of mixtures composed of [C(4)mim][NTf(2)]
      + [C(n)mim][NTf(2)] (n = 1, 2, 5, 6, 8, and 10) was experimentally determined, at
      298.2 K and atmospheric pressure, in the whole composition range. From the
      experimental data, the surface tension deviations and the relative Gibbs
      adsorption isotherms were estimated showing how the surface composition of an
      ionic liquid mixture differs from that of the liquid bulk and that the surface is
      enriched by the ionic liquid with the longest alkyl chain length. Finally, the
      soft-SAFT equation of state coupled with the density gradient theory (DGT) was
      used, for the first time, to successfully reproduce the surface tension
      experimental data of binary mixtures of ionic liquids using a molecular-based
      approach. In addition, the DGT was used to compute the density profiles of the
      two components across the interface, confirming the experimental results for the
      components distribution at the bulk and at the vapor-liquid interface.

PMID- 22963644
TI  - What have we learnt about the causes of ADHD?
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and its possible
      causes still attract controversy. Genes, pre and perinatal risks, psychosocial
      factors and environmental toxins have all been considered as potential risk
      factors. METHOD: This review (focussing on literature published since 1997,
      selected from a search of PubMed) critically considers putative risk factors with
      a focus on genetics and selected environmental risks, examines their
      relationships with ADHD and discusses the likelihood that these risks are causal
      as well as some of the main implications. RESULTS: No single risk factor explains
      ADHD. Both inherited and noninherited factors contribute and their effects are
      interdependent. ADHD is familial and heritable. Research into the inherited and
      molecular genetic contributions to ADHD suggest an important overlap with other
      neurodevelopmental problems, notably, autism spectrum disorders. Having a
      biological relative with ADHD, large, rare copy number variants, some small
      effect size candidate gene variants, extreme early adversity, pre and postnatal
      exposure to lead and low birth weight/prematurity have been most consistently
      found as risk factors, but none are yet known to be definitely causal. There is a
      large literature documenting associations between ADHD and a wide variety of
      putative environmental risks that can, at present, only be regarded as
      correlates. Findings from research designs that go beyond simply testing for
      association are beginning to contest the robustness of some environmental
      exposures previously thought to be ADHD risk factors. CONCLUSIONS: The genetic
      risks implicated in ADHD generally tend to have small effect sizes or be rare and
      often increase risk of many other types of psychopathology. Thus, they cannot be
      used for prediction, genetic testing or diagnostic purposes beyond what is
      predicted by a family history. There is a need to consider the possibility of
      parents and siblings being similarly affected and how this might impact on
      engagement with families, influence interventions and require integration with
      adult services. Genetic contributions to disorder do not necessarily mean that
      medications are the treatment of choice. We also consider how findings might
      influence the conceptualisation of ADHD, public health policy implications and
      why it is unhelpful and incorrect to dichotomise genetic/biological and
      environmental explanations. It is essential that practitioners can interpret
      genetic and aetiological research findings and impart informed explanations to
      families.

PMID- 22963645
TI  - Use of inert gas jets to measure the forces required for mechanical gene
      transfection.
AB  - BACKGROUND: Transferring genes and drugs into cells is central to how we now
      study, identify and treat diseases. Several non-viral gene therapy methods that
      rely on the mechanical disruption of the plasma membrane have been proposed, but
      the success of these methods has been limited due to a lack of understanding of
      the mechanical parameters that lead to cell membrane permeability. METHODS: We
      use a simple jet of inert gas to induce local transfection of plasmid DNA both in
      vitro (HeLa cells) and in vivo (chicken chorioallantoic membrane). Five different
      capillary tube inner diameters and three different gases were used to treat the
      cells to understand the dependency of transfection efficiency on the dynamic
      parameters. RESULTS: The simple setup has the advantage of allowing us to
      calculate the forces acting on cells during transfection. We found
      permeabilization efficiency was related to the dynamic pressure of the jet. The
      range of dynamic pressures that led to transfection in HeLa cells was small (200
      +/- 20 Pa) above which cell stripping occurred. We determined that the temporary
      pores allow the passage of dextran up to 40 kDa and reclose in less than 5
      seconds after treatment. The optimized parameters were also successfully tested
      in vivo using the chorioallantoic membrane of the chick embryo. CONCLUSIONS: The
      results show that the number of cells transfected with the plasmid scales with
      the dynamic pressure of the jet. Our results show that mechanical methods have a
      very small window in which cells are permeabilized without injury (200 to 290
      Pa). This simple apparatus helps define the forces needed for physical cell
      transfection methods.

PMID- 22963647
TI  - Survival of Escherichia coli, enterococci and Campylobacter jejuni in Canada
      goose faeces on pasture.
AB  - Freshly excreted Canada goose faeces pose a public health risk as they contain
      pathogenic microorganisms. Accordingly, a study was carried out on the growth and
      survival of resident indicator bacteria (enterococci and Escherichia coli) and
      inoculated Campylobacter jejuni in freshly excreted faeces over summer and
      winter. Canada goose faeces were collected, mixed thoroughly and inoculated with
      108 g-1 C. jejuni. The faeces were mixed again before making the Canada goose
      dropping. The simulated goose droppings (N = 70) were placed on pasture, and the
      concentrations of E. coli, enterococci and the pathogen, C. jejuni, were
      monitored. In summer only, the molecular marker of E. coli LacZ and the avian
      associated bacteria E2 was also monitored. Results of the survival study
      indicated that significant growth of enterococci and E. coli occurred in summer,
      before concentrations decreased to less than 15% of the original concentration
      (day 77) for enterococci and 0.01% for E. coli. LacZ followed a similar pattern
      to E. coli, while the E2 marker dropped to below 0.1% of the original
      concentration within 4 days. In winter, enterococci grew slightly, while no
      growth of E. coli occurred. In both summer and winter, C. jejuni was rapidly
      inactivated. This research highlights the ability of bacterial indicators to
      replicate and survive in the environment when harboured by avian faeces, and the
      limited risk aged Canada goose faeces pose as an environmental source of
      Campylobacter spp.

PMID- 22963648
TI  - Effect of different host plants on nutritional indices of the pod borer,
      Helicoverpa armigera.
AB  - Nutritional indices of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) on
      different host plants including chickpea (cultivars Arman, Hashem, Azad, and
      Binivich), common bean (cultivar Khomein), white kidney bean (cultivar Dehghan),
      red kidney bean (cultivar Goli), cowpea (cultivar Mashhad), tomato (cultivar
      Meshkin) and potato (cultivars Agria and Satina) were studied under laboratory
      conditions (25 +/- 1  degrees C, 65 +/- 5% RH, 16:8 L:D). Third instar larvae
      reared on potato Agria showed the highest efficiency of conversion of digested
      food (ECD) and efficiency of conversion of ingested food (ECI) (50.800 +/- 0.104%
      and 13.630 +/- 0.016%, respectively). Approximate digestibility (AD) values of
      the fourth instar larvae were highest (92.651 +/- 0.004%) and lowest (57.140 -
      0.049%) on chickpea Azad and potato Agria, respectively. The fifth instar larvae
      fed on tomato Meshkin and white kidney bean Dehghan had the highest consumption
      index (CI) (3.717 +/- 0.091) and relative consumption rate (RCR) (1.620 +/-
      0.074), respectively. Whole larval instars showed the highest ECI and ECD values
      on potatoes Satina (14.640 +/- 0.014%) and Agria (21.380 +/- 0.015%),
      respectively, and the lowest of both values on tomato Meshkin (ECI: 5.748 +/-
      0.002% and ECD: 7.341 +/- 0.002%). The results of nutritional indices and the
      cluster analysis indicated that tomato Meshkin was an unsuitable host for feeding
      of H. armigera.

PMID- 22963649
TI  - Reciprocal influence of alliance to the group and outcome in day treatment for
      eating disorders.
AB  - The nature of the alliance-outcome relationship is still emerging. This study
      examined the reciprocal influence of change in alliance to the group and change
      in urge to restrict in eating-disordered individuals attending a group-based day
      treatment. Participants (N = 238) were a transdiagnostic or mixed diagnostic
      sample of eating-disordered individuals consecutively admitted to a day treatment
      program. On a weekly basis, participants completed a measure of alliance to the
      group of patients with whom they attended multiple group therapies each week.
      After each meal, they rated the intensity of their urge to restrict food intake,
      and the intensity ratings were averaged per week. Latent change score analysis
      was used to assess the reciprocal relationship between prior change in alliance
      to the group with subsequent change in urge to restrict, and prior change in urge
      to restrict with subsequent change in alliance to the group across each
      participant's first 9 weeks in the program. A reciprocal causal model was a good
      fit to the data. Prior growth in alliance to the group was significantly
      associated with subsequent reduction in urge to restrict, and concurrently, prior
      reduction in urge to restrict was significantly associated with subsequent growth
      in alliance to the group. Alliance to the group and individual outcomes are
      dynamically related and changing constructs represented by a reciprocal causal
      model. Clinicians may improve group treatment by assessing alliance to the group
      and outcomes repeatedly, being aware of their interplay, and structuring
      interventions based on the mutual causal effects of change in each.

PMID- 22963650
TI  - Chebulic acid attenuates ischemia reperfusion induced biochemical alteration in
      diabetic rats.
AB  - CONTEXT: Diabetic nephropathy is one of the important microvascular complications
      of diabetes; however, the main problem remains is the control of progression of
      nephropathy in diabetes. Chebulic acid was selected, as tannins from Terminalia
      chebula are used as antidiabetic, renoprotective, antioxidant, hypotensive and an
      alpha-glucosidase inhibitor. OBJECTIVE: In this study, we evaluated the effect of
      chebulic acid on ischemia reperfusion induced biochemical alteration in diabetic
      rats. MATERIALS AND METHODS: Chebulic acid (CA) was isolated from T. chebula;
      LD(50) and acute toxicity studies of CA were done. Renal ischemia and reperfusion
      technique was used to induce nephropathy in diabetic rats. Glibenclamide (10
      mg/kg) was used as diabetic standard; CA at doses of 25 and 50 mg/kg were
      administered for 28 days and various biochemical parameters were monitored.
      RESULTS: The LD(50) was found to be 251 mg/kg; 25 and 50 mg/kg doses were
      selected as no toxic symptoms were observed at both doses, except slight
      diarrhea. CA significantly (p < 0.001) reduced the glucose, creatinine, urea
      nitrogen, glycosylated hemoglobulin, proteinuria, urine albumin excretion,
      glomerular filtration rate (GFR), and increased serum insulin and glycogen level.
      CA also restored glucose 6-phosphate dehydrogenase, glutathione, superoxide
      dismutase, catalase and malondialdehyde levels. Improvement in kidney was also
      noted in histopathological studies. CONCLUSIONS: The statistical data indicated
      that chebulic acid at both doses (25 and 50 mg/kg) improves biochemical
      alterations caused by renal ischemia in diabetic rats.

PMID- 22963652
TI  - Redox-neutral alpha-cyanation of amines.
AB  - alpha-Aminonitriles inaccessible by traditional Strecker chemistry are obtained
      in redox-neutral fashion by direct amine alpha-cyanation/N-alkylation or
      alternatively, alpha-aminonitrile isomerization. These unprecedented
      transformations are catalyzed by simple carboxylic acids.

PMID- 22963653
TI  - pH-controlled release of proteins from polyelectrolyte-modified anodized titanium
      surfaces for implant applications.
AB  - Titanium is a popular choice of implant material given its strength, durability,
      and biocompatibility; however, strong interfaces with the surrounding tissue are
      not achieved, resulting in stress shielding and implant loosening. One option for
      improving adhesion is modification of the surface chemistry and topography
      through anodization, while another option is coating the titanium surface with a
      protein-eluting polyelectrolyte complex. Morphogenetic proteins such as BMP-2
      have been shown to cause cell migration, expression of different genes, and
      development of different tissues. Anodization was used to form a porous oxide
      structure across the surface. A polyelectrolyte coating of poly-l-histidine and
      poly(methacrylic acid) was prepared and was shown to be effective for sustained
      release of negatively charged species under physiological conditions. This
      complex demonstrated pH-dependent release, with maximum release at pH = 5-6, but
      low levels of sustained release at pH = 7-8. Smaller initial burst release and
      higher amounts of sustained release were observed when lower molecular weight
      poly(methacrylic acid) was used. Different methods of loading the polyelectrolyte
      with the model species were compared. Immersion of the coating for loading
      provided greater release, albeit a larger initial burst release.

PMID- 22963651
TI  - Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage
      and retinal ganglion cell loss in experimental optic neuritis.
AB  - BACKGROUND: Optic neuritis is an acute, demyelinating neuropathy of the optic
      nerve often representing the first appreciable symptom of multiple sclerosis.
      Wallerian degeneration of irreversibly damaged optic nerve axons leads to death
      of retinal ganglion cells, which is the cause of permanent visual impairment.
      Although the specific mechanisms responsible for triggering these events are
      unknown, it has been suggested that a key pathological factor is the activation
      of immune-inflammatory processes secondary to leukocyte infiltration. However, to
      date, there is no conclusive evidence to support such a causal role for
      infiltrating peripheral immune cells in the etiopathology of optic neuritis.
      METHODS: To dissect the contribution of the peripheral immune-inflammatory
      response versus the CNS-specific inflammatory response in the development of
      optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in
      wild-type and GFAP-IkappaBalpha-dn transgenic mice, where NF-kappaB is
      selectively inactivated in astrocytes, following induction of EAE. RESULTS: We
      found that, in wild-type mice, axonal demyelination in the optic nerve occurred
      as early as 8 days post induction of EAE, prior to the earliest signs of
      leukocyte infiltration (20 days post induction). On the contrary, GFAP
      IkappaBalpha-dn mice were significantly protected and showed a nearly complete
      prevention of axonal demyelination, as well as a drastic attenuation in retinal
      ganglion cell death. This correlated with a decrease in the expression of pro
      inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention
      of NAD(P)H oxidase subunit upregulation. CONCLUSIONS: Our results provide
      evidence that astrocytes, not infiltrating immune cells, play a key role in the
      development of optic neuritis and that astrocyte-mediated neurotoxicity is
      dependent on activation of a transcriptional program regulated by NF-kappaB.
      Hence, interventions targeting the NF-kappaB transcription factor in astroglia
      may be of therapeutic value in the treatment of optic neuritis associated with
      multiple sclerosis.

PMID- 22963654
TI  - Mechanistic and sterochemical insights on the Pt-catalyzed rearrangement of
      oxiranylpropargylic esters to cyclopentenones.
AB  - A mechanism for the rearrangement of oxiranylpropargylic esters to
      cyclopentenones catalyzed by PtCl(2) is proposed based on DFT calculations (M06/6
      31++G(d,p)). Although the basic steps are coincidental with those proposed by
      Sarpong et al., who characterized a 2H-pyran as intermediate, calculations have
      revealed other intricate details of this complex rearrangement. The 2H-pyran is
      proposed to result from the ring-opening of a bicyclic oxonium ion that follows
      the nucleophilic capture by the epoxide of a platinum carbene generated by an
      initial Pt-mediated 1,2-propargylic rearrangement. The key steps in the evolution
      of this system are the electrocyclic ring-opening of the 2H-pyran to a alpha
      methoxycarbonyl dienone and an iso-Nazarov ring closure. Prior to those, changes
      in hapticity and in the conformation of the dienone are required in order to
      produce the helical conformation needed to generate a single diastereomer of the
      cyclopentenone product obtained experimentally. The metal is needed well beyond
      the first step of the mechanism, and both electrocyclic reactions are favored by
      coordination to the metal when compared to their uncomplexed counterparts.
      Moreover, we have experimentally demonstrated that the rearrangement is
      stereoconvergent, a feature that is traced back to the initial configuration of
      the epoxide, which determines the somewhat counterthermodynamic placement of the
      metal syn to the methyl group of the stereogenic center in the 2H-pyran
      intermediate. Finally, starting from enantiopure oxiranylpropargylic ester 13, a
      racemate of cyclopentenone (R*,S*)-16 was obtained. Thus, the sequence does not
      proceed with memory of chirality, and the absolute stereochemical information is
      already lost at the stage of the 2H-pyran 14.

PMID- 22963655
TI  - Aflatoxins in food products consumed in Brazil: a preliminary dietary risk
      assessment.
AB  - A preliminary dietary exposure assessment for aflatoxins (AFs; AFB1, AFB2, AFG1
      and AFG2) was conducted to evaluate the potential carcinogenic risks for the
      Brazilian population. AF concentration data in food were obtained from analysis
      reports issued by the Central Public Health Laboratory of the Federal District
      (LACEN-DF) and from published work. Food consumption and body weight (bw) data
      were obtained from a national survey conducted in 2008/2009. Cancer risks arising
      from exposure to aflatoxins were assessed using the carcinogenic potency of AFs
      estimated by the JECFA, and hepatitis B virus prevalence in the Brazilian
      population. Additionally, margins of exposure (MOE) were also calculated for the
      various scenarios investigated. A total of 942 food samples were analysed for AFs
      in the Federal District between 2002 and 2011 with 4.5% of them being positive
      for at least one aflatoxin (LOQ = 2 ug kg(-1)). The highest percentage of
      contamination was found in peanuts (8.1%) and Brazil nuts (6.0%), with mean
      levels ranging from 6.7 ug kg(-1) in peanut products to 36.9 ug kg(-1) in Brazil
      nuts. Most of the studies conducted elsewhere in Brazil found similar results.
      Total AF intake for the total Brazilian population and high consumers of food
      relevant for AF contamination in Brazil (upper bound; samples < LOQ = 0.5 LOQ)
      were 6.8 and 27.6 ng kg(-1) bw day(-1), respectively. Cancer risk reached 0.0753
      cancers year(-1) per 10(5) individuals for the total population and 0.3056
      cancers year(-1) per 10(5) individuals for high consumers. MOE reached 25 and 6
      for the total population and high consumers, respectively, indicating a potential
      risk for consumers. Aflatoxins are genotoxic carcinogens, and government action
      should be maintained and continuously improved in order to guarantee that human
      exposure levels are kept as low as possible.

PMID- 22963656
TI  - Clinical features and histological findings are potential indicators of activity
      in lesions of common vitiligo.
AB  - BACKGROUND: Unstable vitiligo lesions are usually considered to be
      contraindications for surgical treatment. Unfortunately, in the majority of
      common vitiligo cases, neither accurate clinical signs nor routine blood tests
      are available to determine whether or not the disease is active. OBJECTIVES: To
      establish a direct correlation between the clinical aspect of vitiligo lesions
      and their activity. METHODS: This was a prospective observational study that took
      place over 1 year. For each patient, a standardized evaluation included both a
      careful daylight and Wood's lamp examination, pictures, biopsies performed at the
      marginal area and histological and immunohistological studies. A second
      examination to assess the activity of the lesions correctly was performed 1 year
      after inclusion in the study. Both the clinical changes and the histological
      features of the lesions in actively spreading vitiligo were compared with those
      in stable vitiligo. RESULTS: This study included 50 patients. The lesions were
      classified as hypomelanotic with poorly defined borders (HPDB, 29 cases) or
      amelanotic with sharply demarcated borders (ASDB, 21 cases). One year after the
      biopsy, of the 48 patients still in the study, 20 had lesions that were
      considered to be stable and 28 had active lesions. Correlations were successfully
      obtained between clinical aspects, histological findings and vitiligo activity.
      The HPDB and ASDB lesions were correlated respectively with active and stable
      status (P < 0.001). CONCLUSIONS: A simple clinical examination including a Wood's
      lamp examination may allow reliable and efficient evaluation of the stability of
      vitiligo lesions.

PMID- 22963657
TI  - Accurate atom-mapping computation for biochemical reactions.
AB  - The complete atom mapping of a chemical reaction is a bijection of the reactant
      atoms to the product atoms that specifies the terminus of each reactant atom.
      Atom mapping of biochemical reactions is useful for many applications of systems
      biology, in particular for metabolic engineering where synthesizing new
      biochemical pathways has to take into account for the number of carbon atoms from
      a source compound that are conserved in the synthesis of a target compound.
      Rapid, accurate computation of the atom mapping(s) of a biochemical reaction
      remains elusive despite significant work on this topic. In particular, past
      researchers did not validate the accuracy of mapping algorithms. We introduce a
      new method for computing atom mappings called the minimum weighted edit-distance
      (MWED) metric. The metric is based on bond propensity to react and computes
      biochemically valid atom mappings for a large percentage of biochemical
      reactions. MWED models can be formulated efficiently as Mixed-Integer Linear
      Programs (MILPs). We have demonstrated this approach on 7501 reactions of the
      MetaCyc database for which 87% of the models could be solved in less than 10 s.
      For 2.1% of the reactions, we found multiple optimal atom mappings. We show that
      the error rate is 0.9% (22 reactions) by comparing these atom mappings to 2446
      atom mappings of the manually curated Kyoto Encyclopedia of Genes and Genomes
      (KEGG) RPAIR database. To our knowledge, our computational atom-mapping approach
      is the most accurate and among the fastest published to date. The atom-mapping
      data will be available in the MetaCyc database later in 2012; the atom-mapping
      software will be available within the Pathway Tools software later in 2012.

PMID- 22963658
TI  - Feasibility and outcomes of laparoscopic renal intervention after prior open
      ipsilateral retroperitoneal surgery.
AB  - BACKGROUND AND PURPOSE: Treating patients with renal-cell carcinoma (RCC) after
      previous retroperitoneal surgery (renal or adrenal) is technically challenging.
      We present our initial experience with laparoscopic renal interventions (LRI)
      after previous open retroperitoneal surgery in patients needing ipsilateral renal
      intervention. We report on feasibility, functional and oncologic outcomes of LRI
      after previous open retroperitoneal surgery. PATIENTS AND METHODS: We reviewed
      records of patients undergoing attempted laparoscopic or robot-assisted renal
      intervention after at least one previous open ipsilateral retroperitoneal
      surgery. We identified 34 patients who underwent 39 staged attempted LRI after 48
      previous open ipsilateral renal or adrenal surgeries. The LRI included 20
      minimally invasive partial nephrectomies (MIPN), 11 laparoscopic radiofrequency
      ablations (LRFA), and 8 laparoscopic nephrectomies (LTN). Demographic,
      perioperative, renal functional, and oncologic outcome data were collected.
      Statistical analyses were performed to identify risks for conversion to open
      surgery. RESULTS: No attempted nephron-sparing procedure resulted in kidney loss.
      Overall conversion rate of the cohort was 28% and was highest in the MIPN group
      (40%). On univariate analysis, only multiple tumors that were treated
      significantly increased chances of open conversion (P<0.01). Subset analysis
      demonstrated similar rates of blood loss, operative times, and conversion rates
      in patients undergoing partial nephrectomy having previous open partial
      nephrectomy compared with previous open adrenal surgery only. There was no
      significant difference in preservation of renal function between MIPN and LRFA,
      with more than 85% of preoperative renal function preserved. Mean follow-up of
      11.9 months (range 1-97.5 mos) metastasis-free survival and overall survival was
      94.1% and 97%, respectively. CONCLUSIONS: LRI after previous open ipsilateral
      retroperitoneal surgery is feasible. Repeated partial nephrectomy has the highest
      conversion risks among the laparoscopic renal interventions and appears to be
      independent of previous renal or adrenal procedure. Attempting repeated LRI for
      multiple tumors is a significant risk factor for open conversion. Renal
      functional and oncologic outcomes are encouraging at early follow-up.

PMID- 22963659
TI  - Antimicrobial activity of bacteriocin-producing lactic acid bacteria isolated
      from cheeses and yogurts.
AB  - The biopreservation of foods using bacteriocinogenic lactic acid bacteria (LAB)
      isolated directly from foods is an innovative approach. The objectives of this
      study were to isolate and identify bacteriocinogenic LAB from various cheeses and
      yogurts and evaluate their antimicrobial effects on selected spoilage and
      pathogenic microorganisms in vitro as well as on a food commodity.LAB were
      isolated using MRS and M17 media. The agar diffusion bioassay was used to screen
      for bacteriocin or bacteriocin-like substances (BLS) producing LAB using
      Lactobacillus sakei and Listeria innocua as indicator organisms. Out of 138 LAB
      isolates, 28 were found to inhibit these bacteria and were identified as strains
      of Enterococcus faecium, Streptococcus thermophilus, Lactobacillus casei and
      Lactobacillus sakei subsp. sakei using 16S rRNA gene sequencing. Eight isolates
      were tested for antimicrobial activity at 5 degrees C and 20 degrees C against L.
      innocua, Escherichia coli, Bacillus cereus, Pseudomonas fluorescens, Erwinia
      carotovora, and Leuconostoc mesenteroides subsp. mesenteroides using the agar
      diffusion bioassay, and also against Penicillium expansum, Botrytis cinerea and
      Monilinia frucitcola using the microdilution plate method. The effect of selected
      LAB strains on L. innocua inoculated onto fresh-cut onions was also
      investigated.Twenty percent of our isolates produced BLS inhibiting the growth of
      L. innocua and/or Lact. sakei. Organic acids and/or H2O2 produced by LAB and not
      the BLS had strong antimicrobial effects on all microorganisms tested with the
      exception of E. coli. Ent. faecium, Strep. thermophilus and Lact. casei
      effectively inhibited the growth of natural microflora and L. innocua inoculated
      onto fresh-cut onions. Bacteriocinogenic LAB present in cheeses and yogurts may
      have potential to be used as biopreservatives in foods.

PMID- 22963660
TI  - Electric-field dependent conformations of single DNA molecules on a model
      biosensor surface.
AB  - Despite the variety of nucleic acid sensors developed, we still do not have
      definite answers to some questions that are important to the molecular binding
      and, ultimately, the sensitivity and reliability of the sensors. How do the DNA
      probes distribute on the surface at the nanoscale? As the functionalized surfaces
      are highly heterogeneous, how are the conformations affected when the probe
      molecules interact with defects? How do DNA molecules respond to electric fields
      on the surface, which are applied in a variety of detection methods? With in situ
      electrochemical atomic force microscopy and careful tailoring of nanoscale
      surface interactions, we are able to observe the nanoscale conformations of
      individual DNA molecules on a model biosensor surface: thiolated DNA on a gold
      surface passivated with a hydroxyl-terminated alkanethiol self-assembled
      monolayer. We find that under applied electric fields, the conformations are
      highly sensitive to the choice of the alkanethiol molecule. Depending on the
      monolayer and the nature of the defects, the DNA molecules may either adopt a
      highly linear or a highly curved conformation. These unusual structures are
      difficult to observe through existing "ensemble" characterizations of nucleic
      acid sensors. These findings provide a step toward correlating target-binding
      affinity, selectivity, and kinetics to the nanoscale chemical structure of and
      around the probe molecules in practical nucleic acid devices.

PMID- 22963661
TI  - Clinical outcome and predictors of survival and pneumonitis after stereotactic
      ablative radiotherapy for stage I non-small cell lung cancer.
AB  - BACKGROUND: Stereotactic ablative radiotherapy (SABR) can achieve excellent local
      control rates in early-stage non-small cell lung cancer (NSCLC) and has emerged
      as a standard treatment option for patients who cannot undergo surgery or those
      with isolated recurrences. However, factors that may predict toxicity or survival
      are largely unknown. We sought here to identify predictors of survival and
      pneumonitis after SABR for NSCLC in a relatively large single-institution series.
      METHODS: Subjects were 130 patients with stage I NSCLC treated with four
      dimensional computed tomography (4D CT) -planned, on-board volumetric image
      guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission
      tomography/computed tomography (PET/CT) and scans were obtained again at the
      second follow-up after SABR. RESULTS: At a median follow-up time of 26 months,
      the 2-year local control rate was 98.5%. The median overall survival (OS) time
      was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at
      3 years. No patient experienced grade 4-5 toxicity; 15 had radiation pneumonitis
      (12 [9.3%] grade 2 and 3 [2.3%] grade 3). Performance status, standardized uptake
      value (SUV)max on staging PET/CT, tumor histology, and disease operability were
      associated with OS on univariate analysis, but only staging SUV(max) was
      independently predictive on multivariate analysis (P = 0.034). Dosimetric factors
      were associated with radiation pneumonitis on univariate analysis, but only mean
      ipsilateral lung dose >= 9.14 Gy was significant on multivariate analysis (P =
      0.005). CONCLUSIONS: OS and radiation pneumonitis after SABR for stage I NSCLC
      can be predicted by staging PET SUV(max) and ipsilateral mean lung dose,
      respectively.

PMID- 22963662
TI  - CO2 capture in alkanolamine-RTIL blends via carbamate crystallization: route to
      efficient regeneration.
AB  - One of the major drawbacks of aqueous alkanolamine based CO(2) capture processes
      is the requirement of significantly higher energy of regeneration. This weakness
      can be overcome by separating the CO(2)-captured product to regenerate the
      corresponding amine, thus avoiding the consumption of redundant energy. Replacing
      aqueous phase with more stable and practically nonvolatile imidazolium based room
      temperature ionic liquid (RTIL) provided a viable approach for carbamate to
      crystallize out as supernatant solid. In the present study, regeneration
      capabilities of solid carbamates have been investigated. Diethanolamine (DEA)
      carbamate as well as 2-amino-2-methyl-1-propanol (AMP) carbamate were obtained in
      crystalline form by bubbling CO(2) in alkanolamine-RTIL mixtures. Hydrophobic
      RTIL, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      ([hmim][Tf(2)N]), was used as aqueous phase substituent. Thermal behavior of the
      carbamates was observed by differential scanning calorimetry and
      thermogravimetric analysis, while the possible regeneration mechanism has been
      proposed through (13)C NMR and FTIR analyses. The results showed that
      decomposition of DEA-carbamate commenced at lower temperature (~55  degrees C),
      compared to that of AMP-carbamate (~75  degrees C); thus promising easy
      regeneration. The separation of carbamate as solid phase can offer two-way
      advantage by letting less volume to regenerate as well as by narrowing the gap
      between CO(2) capture and amine regeneration temperatures.

PMID- 22963663
TI  - Complete mitochondrial genome of the Asian freshwater goby Synechogobius
      ommaturus (Perciformes, Gobioidei).
AB  - The Asian freshwater goby, Synechogobius ommaturus (Perciformes, Gobiidae) is a
      big goby inhabiting shallow sandy-muddy bottoms in temperate riverine estuaries
      and inner bays, mainly distributed in China, Japan, and the Korean Peninsula. In
      this paper, the complete mitochondrial genome of S. ommaturus was firstly
      determined. The genome is 16,660 bp in length and consists of 13 protein-coding
      genes, 22 tRNA genes, 2 ribosomal RNA genes, and 2 main non-coding regions (the
      control region and the origin of the light strand replication). The overall base
      composition of S. ommaturus is 26.9% for T, 27.9% for C, 27.7% for A, and 17.4%
      for G, with a slight A+T bias of 54.6%. It has the typical vertebrate
      mitochondrial gene arrangement.

PMID- 22963664
TI  - Emerging concepts on inhibitors of indoleamine 2,3-dioxygenase in rheumatic
      diseases.
AB  - The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and
      adaptive immune responses through the degradation of the essential amino acid
      tryptophan into kynurenine and other downstream metabolites, which suppress
      effector T-cell function and promote the differentiation of regulatory T cells. A
      novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory
      responses is now emerging. In particular, IDO1 can either support or antagonize
      inflammation in a context- and tissuedependent manner. Studies in experimental
      arthritis have unravelled a previously unappreciated role for IDO in controlling
      B-cell activation and autoantibody production. IDO dysregulation has been
      documented in patients with systemic lupus erythematosus, systemic sclerosis and
      Sjogren's syndrome, as well as in severe sepsis and chronic kidney disease. This
      article summarizes the contribution of IDO to the pathophysiology of
      inflammatory/autoimmune disorders, and discusses whether strategies to restore
      metabolic equilibrium in the kynurenine pathway might be pursued in diseases
      states such as rheumatoid arthritis and systemic sclerosis.

PMID- 22963665
TI  - Bone metastases and non-small cell lung cancer: from bisphosphonates to targeted
      therapy.
AB  - About 30-40% of patients affected by non-small cell lung cancer (NSCLC) develop,
      during the course of their disease, bone metastases. The prognosis of these
      patients is poor with a median survival of less than 1 year. The therapeutic
      approach includes: palliative radiotherapy, and systemic therapy. In clinical
      practice, zoledronate is the most commonly used bisphosphonate to prevent, reduce
      the incidence and delay the onset of skeletal-related events in patients with
      metastatic NSCLC. However, an Italian Association of Thoracic Oncology (AIOT)
      survey, conducted to evaluate how bisphosphonates were used in clinical practice
      for the treatment of lung cancer bone metastases in Italy, showed that the
      bisphosphonates treatment is still not routine and varies in duration. Denosumab
      is a fully human monoclonal antibody directed against the receptor activator of
      nuclear factor kappa-B (RANK)-Ligand inhibiting the maturation of pre-osteoclasts
      into osteoclasts and is the first example of targeted therapy for bone
      metastases. An exploratory analysis showed that denosumab was associated with
      improved overall survival compared with zoledronate in patients with bone
      metastases from lung cancer. Biochemical markers of bone turnover to predict what
      patients are at greatest risk of developing skeletal-related events, and to
      direct treatment of bone metastases with either bisphosphonates or denosumab, are
      under investigation. This review is focused on the systemic management of bone
      metastases from NSCLC.

PMID- 22963666
TI  - Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization.
AB  - The therapeutic potential of gallic acid and its derivatives as anti-cancer,
      antimicrobial and antiviral agents is well known. We have examined the mechanism
      by which natural gallic acid and newly synthesized gallic acid alkyl esters and
      related protocatechuic acid alkyl esters inhibit HIV-1 protease to compare the
      influence of the aromatic ring substitutions on inhibition. We used Zhang
      Poorman's kinetic analysis and fluorescent probe binding to demonstrate that
      several gallic and protecatechuic acid alkyl esters inhibited HIV-1 protease by
      preventing the dimerization of this obligate homodimeric aspartic protease rather
      than targeting the active site. The tri-hydroxy substituted benzoic moiety in
      gallates was more favorable than the di-substituted one in protocatechuates. In
      both series, the type of inhibition, its mechanism and the inhibitory efficiency
      dramatically depended on the length of the alkyl chain: no inhibition with alkyl
      chains less than 8 carbon atoms long. Molecular dynamics simulations corroborated
      the kinetic data and propose that gallic esters are intercalated between the two
      N- and C-monomer ends. They complete the beta-sheet and disrupt the dimeric
      enzyme. The best gallic ester (14 carbon atoms, K(id) of 320 nM) also inhibited
      the multi-mutated protease MDR-HM. These results will aid the rational design of
      future generations of non-peptide inhibitors of HIV-1 protease dimerization that
      inhibit multi-mutated proteases. Finally, our work suggests the wide use of
      gallic and protocatechuic alkyl esters to dissociate intermolecular beta-sheets
      involved in protein-protein interactions.

PMID- 22963667
TI  - Snake venom phospholipases A(2): a novel tool against bacterial diseases.
AB  - The majority of snake venom phospholipases A(2) (svPLA(2)s) are toxic and induce
      a wide spectrum of biological effects. They are cysteine-rich proteins that
      contain 119-134 amino acids and share similar structures and functions. About 50%
      of the residues are incorporated into alpha-helices, whereas only 10% are in beta
      sheets. Fourteen conserved cysteines form a network of seven disulfide bridges
      that stabilize the tertiary structure. They show a high degree of sequence and
      structural similarity, and are believed to have a common calcium- dependent
      catalytic mechanism. Additionally, svPLA(2)s display an array of biological
      actions that are either dependent or independent of catalysis. The PLA(2)s of
      mammalian origin also exert potent bactericidal activity by binding to anionic
      surfaces and enzymatic degradation of phospholipids in the target membranes,
      preferentially of Gram-positive species. The bactericidal activity against Gram
      negatives by svPLA(2) requires a synergistic action with
      bactericidal/permeability-increasing protein (BPI), but is equally dependent on
      enzymatic- based membrane degradation. Several hypotheses account for the
      bactericidal properties of svPLA(2)s, which include "fatal depolarization" of the
      bacterial membrane, creation of physical holes in the membrane, scrambling of
      normal distribution of lipids between the bilayer leaflets, and damage of
      critical intracellular targets after internalization of the peptide. The present
      review discusses several svPLA(2)s and derived peptides that exhibit strong
      bactericidal activity. The reports demonstrate that svPLA(2)-derived peptides
      have the potential to counteract microbial infections. In fact, the C-terminal
      cationic/hydrophobic segment (residues 115-129) of svPLA(2)s is bactericidal.
      Thus identification of the bactericidal sites in svPLA(2)s has potential for
      developing novel antimicrobials.

PMID- 22963668
TI  - Recent advances in the structure-based design of neuraminidase inhibitors as
      antiinfluenza agents.
AB  - Influenza is an infection of the upper respiratory tract caused by influenza
      virus. Neuraminidase (NA) plays an essential role in replication and infection of
      influenza virus. It is considered as a suitable target for antivirus agents
      development. Several potent NA inhibitors (NAIs) developed by using structure
      based rational design have been widely used in clinic for treatment of influenza.
      However, the emergence of NA inhibitor-resistant virus mutations significantly
      limit their effectiveness. The molecular basis of virus resistance to NAIs has
      been a focus of intensive research. This review highlights recent progress in
      rational design and resistance mechanism of NAIs. We hope this review will be
      useful to not only researchers who are interested in developing novel NAIs but
      also clinical pharmacists.

PMID- 22963670
TI  - Lactate dehydrogenase as an indicator of severe illness in neonatal intensive
      care patients: a longitudinal cohort study.
AB  - AIM: Lactate dehydrogenase (LDH) increases in several critical conditions that
      cause cell damage and could potentially be used for early detection of serious
      illness in the newborn. Our aim was to investigate the relationship between the
      early clinical course of NICU infants and LDH in plasma at admission. METHODS:
      LDH was measured in a cohort of patients consecutively admitted to a major NICU
      in Hanoi. The infants were classified as 'obviously needing intensive care during
      the first week' (n = 83) or 'not receiving intensive care measures during the
      first week' (n = 260) by a senior neonatologist blinded to the LDH and lactate
      activity. RESULTS: LDH differed significantly between the groups in infants born
      after 32 gestational weeks. LDH differed with the vitality of the patient (F =
      26.25, p < 0.0001) at admittance and correlated with lactate (R = 0.496, p <
      0.0001). Also, the predictive value for obvious need of intensive care was higher
      for LDH than for lactate assessed by area under the curve calculated with ROC
      curves [0.82 (0.77-0.88) vs. 0.67 (0.60-0.75)]. CONCLUSION: There is a strong
      relationship between bad clinical condition of infants during first week of life
      and elevated plasma LDH. The results suggest that LDH might be a valuable support
      in decision making in the neonatal period.

PMID- 22963671
TI  - Understanding the structure factor and isothermal compressibility of ambient
      water in terms of local structural environments.
AB  - We determine contributions to the structure factor of ambient water (modeled
      using the TIP4P/2005 potential) from molecules with different local structural
      environments, distinguished based on a tetrahedral order parameter. The small
      wavenumber behavior of the partial structure factors indicates the presence of
      effective attractive interactions between molecules with similar local
      environments and effective repulsive interactions between molecules with
      different local environments. These effective interactions lead to significant
      concentration fluctuations under ambient conditions. The concentration
      fluctuations correlate with density fluctuations, and provide an explanation for
      the recently reported (Huang et al. Proc. Natl. Acad. Sci. U.S.A.2009, 36, 15214)
      increase in the structure factor at small wavenumber, as well as for the well
      known anomalous temperature dependence of the isothermal compressibility.

PMID- 22963669
TI  - Methyl eugenol: its occurrence, distribution, and role in nature, especially in
      relation to insect behavior and pollination.
AB  - This review discusses the occurrence and distribution (within a plant) of methyl
      eugenol in different plant species (> 450) from 80 families spanning many plant
      orders, as well as various roles this chemical plays in nature, especially in the
      interactions between tephritid fruit flies and plants.

PMID- 22963672
TI  - SIZ1 deficiency causes reduced stomatal aperture and enhanced drought tolerance
      via controlling salicylic acid-induced accumulation of reactive oxygen species in
      Arabidopsis.
AB  - Transpiration and gas exchange occur through stomata. Thus, the control of
      stomatal aperture is important for the efficiency and regulation of water use,
      and for the response to drought. Here, we demonstrate that SIZ1-mediated
      endogenous salicylic acid (SA) accumulation plays an important role in stomatal
      closure and drought tolerance. siz1 reduced stomatal apertures. The reduced
      stomatal apertures of siz1 were inhibited by the application of peroxidase
      inhibitors, salicylhydroxamic acid and azide, which inhibits SA-dependent
      reactive oxygen species (ROS) production, but not by an NADPH oxidase inhibitor,
      diphenyl iodonium chloride, which inhibits ABA-dependent ROS production.
      Furthermore, the introduction of nahG into siz1, which reduces SA accumulation,
      restored stomatal opening. Stomatal closure is generally induced by water
      deficit. The siz1 mutation caused drought tolerance, whereas nahG siz1 suppressed
      the tolerant phenotype. Drought stresses also induced expression of SA-responsive
      genes, such as PR1 and PR2. Furthermore, other SA-accumulating mutants, cpr5 and
      acd6, exhibited stomatal closure and drought tolerance, and nahG suppressed the
      phenotype of cpr5 and acd6, as did siz1 and nahG siz1. Together, these results
      suggest that SIZ1 negatively affects stomatal closure and drought tolerance
      through the accumulation of SA. 

PMID- 22963673
TI  - Submucous rather than myenteric neurons are activated by mucosal biopsy
      supernatants from irritable bowel syndrome patients.
AB  - BACKGROUND: We previously showed that colonic mucosal biopsy supernatants from
      patients with irritable bowel syndrome (IBS) activate neurons of the human
      submucous plexus, an area with densely packed immune cells. Based on the concept
      that mucosa-nerve signaling is altered in IBS, we tested in this study whether
      the nerve sensitizing effect of IBS mucosal biopsy supernatants is more prominent
      in the submucous than myenteric plexus. METHODS: Fast neuroimaging with the
      voltage-sensitive dye Di-8-ANEPPS was used to record activity of guinea-pig
      submucous and myenteric neurons after application of constipation (C)- and
      diarrhea (D)-IBS supernatants (three each) and four supernatants from healthy
      control subjects. Results are based on recordings from 4731 neurons. KEY RESULTS:
      Control supernatants did not evoke significant responses in submucous or
      myenteric neurons. In contrast, all IBS supernatants evoked a significant spike
      discharge (median 3.6 Hz) in 46% of submucous neurons. This activation was
      significantly stronger than in the myenteric plexus where even twice the amount
      of supernatants evoked a lower spike frequency (median 2.1Hz) in only 8.5% of
      neurons. Pharmacological studies revealed serotonin, histamine, and proteases as
      components mediating neuronal activation. Individual application of these
      components revealed that only serotonin evoked a significantly stronger
      activation of submucous compared with myenteric neurons. CONCLUSIONS &
      INFERENCES: Direct neuronal activation by IBS mucosal biopsy supernatants is
      primarily a feature of submucous rather than myenteric neurons. This is
      associated with a stronger excitation of submucous neurons by serotonin. The
      plexus-specific effects support the concept that altered mucosa-nerve signaling
      underlies disturbances in IBS.

PMID- 22963675
TI  - Allelic variations in coding regions of the vitamin D receptor gene in dairy cows
      and potential susceptibility to periparturient hypocalcaemia.
AB  - Periparturient hypocalcaemia (milk fever) is a disorder of Ca metabolism in dairy
      cattle primarily affecting multiparous cows. The major reasons for the rapid
      decrease of blood Ca concentration after calving are the prompt increase of Ca
      secretion into the colostrum and the delayed activation of Ca regulation
      mechanisms including calcitriol, a metabolite of vitamin D. In man, vitamin D
      receptor (VDR) gene polymorphisms are reported to be associated with disturbances
      of Ca metabolism, whereas data confirming the same in dairy cows are still
      missing. Moreover, polymorphisms that only affect non-coding regions are
      sometimes difficult to ascribe to a specific disorder as pathways and unequivocal
      links remain elusive. Therefore, the idea of the present study was to investigate
      in a small group of dairy cows with documented clinical records whether
      polymorphisms in the coding regions of the VDR gene existed and whether these
      potentially found variations were correlated with the incidence of periparturient
      hypocalcaemia. For this purpose, blood DNA was isolated from 26 dairy cows in
      their 4th to 6th lactation, out of which 17 had experienced hypocalcaemia at
      least once, whereas 9 cows had never undergone periparturient hypocalcaemia in
      their lifetime. The 10 VDR exons and small parts of adjacent introns were
      sequenced and compared with the Bos taurus VDR sequence published on NCBI based
      on the DNA of one Hereford cow. In total, 8 sequence alterations were detected in
      the fragments, which were primarily heterozygous. However, only 4 of them were
      really located on exons thereby potentially causing changes of the encoded amino
      acid of the VDR protein, but were not correlated with the incidence of
      periparturient hypocalcaemia. Certainly, this lack of statistical correlation
      could be due to the small number of animals included; anyhow, it was not
      encouraging enough to initiate a larger study with hundreds of cows and document
      blood Ca levels post partum for at least four lactations.

PMID- 22963676
TI  - Gross cystic disease fluid protein-15 and mammaglobin A expression determined by
      immunohistochemistry is of limited utility in triple-negative breast cancer.
AB  - AIMS:   In addition to oestrogen and progesterone receptors, gross cystic disease
      fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers
      used to identify breast origin by immunohistochemistry. GCDFP-15 expression has
      been reported in approximately 60% of breast carcinomas and MAM expression in
      approximately 80%. Data on their expression in triple-negative breast cancer
      (TNBC) are very limited. The aim of this study was to examine the expression of
      these markers in TNBC to determine their utility in pathological diagnosis.
      METHODS AND RESULTS:   We studied the immunohistochemical (IHC) expression of
      GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was
      present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present
      in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of
      GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many
      positive tumours had only focal staining. CONCLUSIONS:   Staining for GCDFP-15
      and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most
      tumours in this subgroup of breast carcinomas lack expression of either marker.

PMID- 22963677
TI  - Nitrogen isotopes link mycorrhizal fungi and plants to nitrogen dynamics.
AB  - In this review, we synthesize field and culture studies of the 15N/14N (expressed
      as delta15N) of autotrophic plants, mycoheterotrophic plants, parasitic plants,
      soil, and mycorrhizal fungi to assess the major controls of isotopic patterns.
      One major control for plants and fungi is the partitioning of nitrogen (N) into
      either 15N-depleted chitin, ammonia, or transfer compounds or 15N-enriched
      proteinaceous N. For example, parasitic plants and autotrophic hosts are similar
      in delta15N (with no partitioning between chitin and protein), mycoheterotrophic
      plants are higher in delta15 N than their fungal hosts, presumably with
      preferential assimilation of fungal protein, and autotrophic, mycorrhizal plants
      are lower in 15N than their fungal symbionts, with saprotrophic fungi
      intermediate, because mycorrhizal fungi transfer 15N-depleted ammonia or amino
      acids to plants. Similarly, nodules of N2-fixing bacteria transferring ammonia
      are often higher in delta15N than their plant hosts. N losses via denitrification
      greatly influence bulk soil delta15N, whereas delta15N patterns within soil
      profiles are influenced both by vertical patterns of N losses and by N transfers
      within the soil-plant system. Climate correlates poorly with soil delta15N;
      climate may primarily influence delta15N patterns in soils and plants by
      determining the primary loss mechanisms and which types of mycorrhizal fungi and
      associated vegetation dominate across climatic gradients.

PMID- 22963674
TI  - Animal models and conserved processes.
AB  - BACKGROUND: The concept of conserved processes presents unique opportunities for
      using nonhuman animal models in biomedical research. However, the concept must be
      examined in the context that humans and nonhuman animals are evolved, complex,
      adaptive systems. Given that nonhuman animals are examples of living systems that
      are differently complex from humans, what does the existence of a conserved gene
      or process imply for inter-species extrapolation? METHODS: We surveyed the
      literature including philosophy of science, biological complexity, conserved
      processes, evolutionary biology, comparative medicine, anti-neoplastic agents,
      inhalational anesthetics, and drug development journals in order to determine the
      value of nonhuman animal models when studying conserved processes. RESULTS:
      Evolution through natural selection has employed components and processes both to
      produce the same outcomes among species but also to generate different functions
      and traits. Many genes and processes are conserved, but new combinations of these
      processes or different regulation of the genes involved in these processes have
      resulted in unique organisms. Further, there is a hierarchy of organization in
      complex living systems. At some levels, the components are simple systems that
      can be analyzed by mathematics or the physical sciences, while at other levels
      the system cannot be fully analyzed by reducing it to a physical system. The
      study of complex living systems must alternate between focusing on the parts and
      examining the intact whole organism while taking into account the connections
      between the two. Systems biology aims for this holism. We examined the actions of
      inhalational anesthetic agents and anti-neoplastic agents in order to address
      what the characteristics of complex living systems imply for inter-species
      extrapolation of traits and responses related to conserved processes. CONCLUSION:
      We conclude that even the presence of conserved processes is insufficient for
      inter-species extrapolation when the trait or response being studied is located
      at higher levels of organization, is in a different module, or is influenced by
      other modules. However, when the examination of the conserved process occurs at
      the same level of organization or in the same module, and hence is subject to
      study solely by reductionism, then extrapolation is possible.

PMID- 22963678
TI  - Ethanol extract of paeonia suffruticosa Andrews (PSE) induced AGS human gastric
      cancer cell apoptosis via fas-dependent apoptosis and MDM2-p53 pathways.
AB  - BACKGROUND: The root bark of Paeonia suffruticosa Andrews (PSE), also known as
      Moutan Cortex, has been widely used in Asia to treat various diseases. The
      molecular mechanisms by which PSE exerts its anti-oxidant and anti-inflammatory
      activities are well known, but its anti-cancer activity is not yet well
      understood. Here, we present evidence demonstrating that PSE can be used as a
      potent anti-cancer agent to treat gastric cancer. METHODS: The effects of the
      ethanol extract of PSE on cell proliferation were determined using an MTT (1-(4,5
      dimethylthiazol-2-yl)-3,5-diphenylformazan) assay. Cell cytotoxicity induced by
      the PSE extact is measured using an LDH leakage assay. Flow cytometry was used to
      analyze the cell cycle and to measure the subG0/G1 apoptotic cell fraction.
      Apoptosis induced by the PSE extact is also examined using a DNA fragmentation
      assay. Western blot analysis is used to measure the levels of apoptotic proteins
      such as Fas receptor, caspase-8, caspase-3, PARP, Bax, Bcl-2, MDM2, and p53.
      RESULTS: This study demonstrated that treating AGS cells with the PSE extact
      significantly inhibited cell proliferation and induced cytotoxicity in a dose-
      and time-dependent manner. The PSE extract also induced apoptosis in AGS cells,
      as measured by flow cytometry and a DNA fragmentation assay. We found that the
      PSE extract induced apoptosis via the extrinsic Fas-mediated apoptosis pathway,
      which was concurrent with the activation of caspases, including caspase-8 and
      caspase-3, and cleavage of PARP. The MDM2-p53 pathway also played a role in the
      apoptosis of AGS cells that was induced by the PSE extract. CONCLUSIONS: These
      results clearly demonstrate that the PSE extact displays growth-suppressive
      activity and induces apoptosis in AGS cells. Our data suggest that the PSE extact
      might be a potential anti-cancer agent for gastric cancer.

PMID- 22963679
TI  - In vitro and in vivo evaluation of antioxidant and antigenotoxic potential of
      Punica granatum leaf extract.
AB  - CONTEXT: Several studies have reported the antioxidant activity and potential
      therapeutic properties of Punica granatum L. (Lythraceae) fruit. Medicinal
      properties have also been attributed to other parts of P. granatum tree, which
      are rich in bioactive phytochemicals. OBJECTIVE: To explore the phytochemical
      characteristics, in vitro and in vivo antioxidant and in vivo antigenotoxic
      potential of P. granatum leaf extract (PLE). MATERIALS AND METHODS: The in vitro
      antioxidant potential of PLE was assessed by DPPH (1,1-diphenyl-2
      picrylhydrazyl), ferric reducing antioxidant power (FRAP). Inhibition of lipid
      peroxidation (LPO) and the total phenolic content of the samples were also
      determined. Thirty-six male Swiss albino mice were divided into six groups (six
      animals each). Group 1 (control) and group 2 mice received vehicle and genotoxin
      alone, respectively. Groups 3, 4 and 5 were pretreated with PLE (400, 600 and 800
      mg/kg body weight, respectively) prior to the administration of genotoxin. Group
      6 received highest test dose of PLE. DNA damage in the bone marrow cells, hepatic
      LPO and antioxidants were recorded. RESULTS: Phytochemical analysis of PLE showed
      the presence of flavonoids, phenols, phytosterols, tannins and carbohydrates.
      Aqueous PLE demonstrated free radical scavenging activity, reducing power and
      inhibition of LPO with the EC50 values of 10.25, 59.88 and 20.05, respectively. A
      significant protective effect was observed against cyclophosphamide induced DNA
      damage and inhibition of hepatic LPO with concomitant increase in reduced
      glutathione (GSH) glutathione S-transferase (GST), superoxide dismutase (SOD) and
      catalase (CAT) in mice pretreated with PLE. DISCUSSION AND CONCLUSION: PLE
      demonstrated a significant antioxidant and antigenotoxic potential and hence can
      be a potential natural source in health and medicine.

PMID- 22963681
TI  - Observation of layer-breathing mode vibrations in few-layer graphene through
      combination Raman scattering.
AB  - We report the observation of layer-breathing mode (LBM) vibrations in few-layer
      graphene (FLG) samples of thickness from two to six layers, exhibiting both
      Bernal (AB) and rhombohedral (ABC) stacking order. The LBM vibrations are
      identified using a Raman combination band lying around 1720 cm(-1). From double
      resonance theory, we assign the feature as the LO+ZO' combination mode of the out
      of-plane LBM (ZO') and the in-plane longitudinal optical mode (LO). The LOZO'
      Raman band is found to exhibit multiple peaks with a unique line shape for each
      layer thickness and stacking order. These complex line shapes of the LOZO'-mode
      arise both from the material-dependent selection of different phonons in the
      double-resonance Raman process and from the detailed structure of the different
      branches of LBM in FLG.

PMID- 22963680
TI  - Methodological considerations in cost of illness studies on Alzheimer disease.
AB  - Cost-of-illness studies (COI) can identify and measure all the costs of a
      particular disease, including the direct, indirect and intangible dimensions.
      They are intended to provide estimates about the economic impact of costly
      disease. Alzheimer disease (AD) is a relevant example to review cost of illness
      studies because of its costliness.The aim of this study was to review relevant
      published cost studies of AD to analyze the method used and to identify which
      dimension had to be improved from a methodological perspective. First, we
      described the key points of cost study methodology. Secondly, cost studies
      relating to AD were systematically reviewed, focussing on an analysis of the
      different methods used. The methodological choices of the studies were analysed
      using an analytical grid which contains the main methodological items of COI
      studies. Seventeen articles were retained. Depending on the studies, annual total
      costs per patient vary from $2,935 to $52, 954. The methods, data sources, and
      estimated cost categories in each study varied widely. The review showed that
      cost studies adopted different approaches to estimate costs of AD, reflecting a
      lack of consensus on the methodology of cost studies. To increase its
      credibility, closer agreement among researchers on the methodological principles
      of cost studies would be desirable.

PMID- 22963682
TI  - Polymerization behavior of a bifunctional ubiquitin monomer as a function of the
      nucleophile site and folding conditions.
AB  - Biopolymers with repeating modules composed of either folded peptides or tertiary
      protein domains are considered some of the basic biomaterials that nature has
      evolved to optimize for energy efficient synthesis and unique functions. Such
      biomaterials continue to inspire scientists to mimic their exceptional properties
      and the ways that nature adopts to prepare them. Ubiquitin chains represent
      another example of nature's approach to use a protein-repeating module to prepare
      functionally important biopolymers. In the current work, we utilize a novel
      synthetic strategy to prepare bifunctional ubiquitin monomers having a C-terminal
      thioester and a nucleophilic 1,2-aminothiol at a desired position to examine
      their polymerization products under different conditions. Our study reveals that
      such analogues, when subjected to polymerization conditions under different
      folding states, afford distinct patterns of polymerization products where both
      the dynamic and the tertiary structures of the chains play important roles in
      such processes. Moreover, we also show that the presence of a specific ubiquitin
      binding domain, which binds specifically to some of these chains, could interfere
      selectively with the polymerization outcome. Our study represents the first
      example of examining the polymerization of designed and synthetic repeating
      modules based on tertiary protein domains and affords early lessons in the design
      and synthesis of biomaterial. In regards to the ubiquitin system, our study may
      have implications on the ease of synthesis of ubiquitin chains with varying
      lengths and types for structural and functional analyses. Importantly, such an
      approach could also assist in understanding the enzymatic machinery and the
      factors controlling the assembly of these chains with a desired length.

PMID- 22963684
TI  - Are the effects of early pubertal timing on the initiation of weekly alcohol use
      mediated by peers and/or parents? A longitudinal study.
AB  - We investigated whether the link between early pubertal timing and initiation of
      weekly alcohol use is mediated by changes in perceived parental alcohol-specific
      rule setting and changes in perceived proportion of drinkers in the peer group.
      Longitudinal data including 3 annual waves were used to estimate the hazard for
      adolescents to initiate drinking alcohol using Cox proportional hazard structural
      equation models in 1,286 Dutch adolescents (50.2% boys) 13-14 years old at
      baseline in 2008. Early pubertal timing increased the risk to initiate weekly
      alcohol use. However, this risk was entirely mediated by a large increase in the
      perceived proportion of drinkers in the peer group and a large decrease in the
      frequency of perceived alcohol-specific rules for early pubertal timers within a
      period of 1 year. There is no direct risk for early pubertal timers to initiate
      weekly drinking per se but an indirect one via changes in their social
      environments, that is, a large increase in the perceived proportion of drinkers
      in their peer group and parents becoming more lenient in their alcohol-specific
      rule setting. It is important to motivate parents not to relax their alcohol
      specific rule setting over time, particularly parents of early pubertal timers.

PMID- 22963683
TI  - Establishment of animal model for the analysis of cancer cell metastasis during
      radiotherapy.
AB  - BACKGROUND: Gamma-Ionizing radiation (IR) therapy is one of major therapeutic
      tools in cancer treatment. Nevertheless, gamma-IR therapy failed due to
      occurrence of metastasis, which constitutes a significant obstacle in cancer
      treatment. The main aim of this investigation was to construct animal model which
      present metastasis during radiotherapy in a mouse system in vivo and establishes
      the molecular mechanisms involved. MATERIALS AND METHODS: The C6L transfectant
      cell line expressing firefly luciferase (fLuc) was treated with gamma-IR,
      followed by immunoblotting, zymography and invasion assay in vitro. We
      additionally employed the C6L transfectant cell line to construct xenografts in
      nude mice, which were irradiated with gamma-IR. Irradiated xenograft-containing
      mice were analyzed via survival curves, measurement of tumor size, and
      bioluminescence imaging in vivo and ex vivo. Metastatic lesions in organs of mice
      were further assessed using RT-PCR, H & E staining and immunohistochemistry.
      RESULTS: gamma-IR treatment of C6L cells induced epithelial-mesenchymal
      transition (EMT) and increased cell invasion. In irradiated xenograft-containing
      mice, tumor sizes were decreased dramatically and survival rates extended. Almost
      all non-irradiated xenograft-containing control mice had died within 4 weeks.
      However, we also observed luminescence signals in about 22.5% of gamma-IR-treated
      mice. Intestines or lungs of mice displaying luminescence signals contained
      several lesions, which expressed the fLuc gene and presented histological
      features of cancer tissues as well as expression of EMT markers. CONCLUSIONS:
      These findings collectively indicate that occurrences of metastases during gamma
      IR treatment accompanied induction of EMT markers, including increased MMP
      activity. Establishment of a murine metastasis model during gamma-IR treatment
      should aid in drug development against cancer metastasis and increase our
      understanding of the mechanisms underlying the metastatic process.

PMID- 22963686
TI  - Current pharmacotherapy options for labor induction.
AB  - INTRODUCTION: Labor induction is now reported to occur in up to 30 - 40% of
      obstetrical patients. There are a number of pharmacological options available to
      facilitate labor induction, including oxytocin and analogues of prostaglandins E1
      and E2, which have particular utility when labor induction necessitates cervical
      ripening, as when labor induction occurs in the context of an unfavorable cervix.
      AREAS COVERED: This paper reviews acceptable pharmacological options for labor
      induction, especially when cervical ripening is required. These options include
      oxytocin and a number of prostaglandin formulations using dinoprostone and
      misoprostol. It also covers several analyses of published clinical trials (Phase
      III) describing evidence of effectiveness. EXPERT OPINION: Oxytocin is best used
      when labor needs to be induced in the context of a favorable cervix. When the
      cervix is not favorable, cervical ripening using prostaglandins should precede
      labor induction. Either dinoprostone or misoprostol are superior to oxytocin
      alone for cervical ripening. However, judicious, careful considerations need to
      be made at the outset of labor induction so as to balance maternal and fetal
      risks, and these should be guided by institutional policies that reflect the
      evidence-base.

PMID- 22963687
TI  - Enhanced screening efficiency for endocrine-disrupting chemicals in milk and
      powdered milk using UPLC/QTOF-MS by the introduction of dansyl chloride
      derivatisation.
AB  - This study developed and validated a sensitive analytical method for simultaneous
      screening of four classes of endocrine-disrupting chemicals (i.e. progestogens,
      androgens, oestrogens and phenols) in milk and powdered milk using ultra
      performance liquid chromatography (UPLC) coupled with electrospray ionisation
      quadrupole time-of-flight mass spectrometry (QTOF-MS). Dansylation of oestrogens
      and phenols enhanced the ionisation efficiency and shifted the ionisation mode
      from negative to positive, which allowed for the simultaneous analysis of four
      EDCs in one chromatographic run. An efficient sample pre-treatment minimised the
      matrix effects. The mass errors for the precursor and product ions for 26 target
      compounds varied between -2.8 and 2.3 mDa; and the limits of detection (signal-to
      noise ratio = 3) for milk and powdered milk were less than 0.04 ug l(-1) and 0.10
      ug kg(-1), respectively. The proposed method was successfully used to analyse
      multiple types of real samples, including normal temperature whole milk, infant
      formula and whole powdered milk. In 11 samples, two target compounds,
      progesterone and androstenedione, were detected. The progesterone concentrations
      ranged from 8.1 to 12.7 ug l(-1) in milk, and from 1.2 to 32.0 ug kg(-1) in
      infant formulas and whole powdered milks. The androstenedione concentrations
      varied from 0.39 to 0.79 ug l(-1) in milks, and from 0.29 to 1.2 ug kg(-1) in
      infant formulas and whole powdered milks. Two post-target compounds, one isomer
      of oestriol and 5alpha-dihydroprogesterone, were tentatively identified by post
      target analysis in two of 11 real samples.

PMID- 22963688
TI  - Biodegradable poly(disulfide)s derived from RAFT polymerization: monomer scope,
      glutathione degradation, and tunable thermal responses.
AB  - Telechelic, RAFT (reversible addition-fragmentation chain transfer)-derived
      macromonomers with a pyridyl disulfide end-group were converted into high
      molecular weight, disulfide-linked polymers using a polycondensation, step-growth
      procedure. The applicability of the method to polycondense a library of
      macromonomers with different functionalities including (meth)acrylates and
      acrylamides was investigated. Side-chain sterics were found to be important as
      nonlinear poly(ethylene glycol) analogues, which proved incompatible with this
      synthetic methodology, as were methacrylates due to their pendant methyl group.
      This method was used to incorporate disulfide bonds into poly(N
      isopropylacrylamide), pNIPAM, precursors to give dual-responsive (thermo- and
      redox) materials. These polymers were shown to selectively degrade in the
      presence of intracellular concentrations of glutathione but be stable at low
      concentrations. Due to the molecular weight-dependent cloud point of pNIPAM, the
      lower critical solution temperature behavior could be switched off by a
      glutathione gradient without a temperature change: an isothermal transition.

PMID- 22963689
TI  - Taking action on developmental toxicity: scientists' duties to protect children.
AB  - BACKGROUND: Although adaptation and proper biological functioning require
      developmental programming, pollutant interference can cause developmental
      toxicity or DT. OBJECTIVES: This commentary assesses whether it is ethical for
      citizens/physicians/scientists to allow avoidable DT. METHODS: Using conceptual,
      economic, ethical, and logical analysis, the commentary assesses what major
      ethical theories and objectors would say regarding the defensibility of allowing
      avoidable DT. RESULTS: The commentary argues that (1) none of the four major
      ethical theories (based, respectively, on virtue, natural law, utility, or
      equity) can consistently defend avoidable DT because it unjustifiably harms,
      respectively, individual human flourishing, human life, the greatest good, and
      equality. (2) Justice also requires leaving "as much and as good" biological
      resources for all, including future generations possibly harmed if epigenetic
      change is heritable. (3) Scientists/physicians have greater justice-based duties,
      than ordinary/average citizens, to help stop DT because they help cause it and
      have greater professional abilities/opportunities to help stop it. (4)
      Scientists/physicians likewise have greater justice-based duties, than
      ordinary/average citizens, to help stop DT because they benefit more from it,
      given their relatively greater education/consumption/income. The paper shows that
      major objections to (3)-(4) fail on logical, ethical, or scientific grounds, then
      closes with practical suggestions for implementing its proposals. CONCLUSIONS:
      Because allowing avoidable DT is ethically indefensible, citizens---and
      especially physicians/scientists---have justice-based duties to help stop DT.

PMID- 22963690
TI  - ZNF281 knockdown induced osteogenic differentiation of human multipotent stem
      cells in vivo and in vitro.
AB  - ZNF281 is one of the core transcription factors in embryonic stem cells (ESCs)
      and has activation and repression roles in the transcription of ESC genes. A
      known target molecule of Zfp281 (the mouse homologue of ZNF281) is Nanog.
      However, NANOG is not expressed in most human multipotent stem cells (hMSCs).
      Here, we investigated the roles of ZNF281 with a gain- and loss-of-function
      study. The knockdown of ZNF281 in vivo and in vitro resulted in spontaneous
      osteochondrogenic differentiation and reduced the proliferation of hMSCs, as
      determined by cell morphology and molecular markers. When ZNF281-knockdown hMSCs
      were subcutaneously implanted into mice along with beta-tricalcium phosphate
      (beta-TCP), many cells were converted into osteoblasts within 4 weeks. In
      contrast, the overexpression of ZNF281 in hMSCs resulted in accelerated
      proliferation. The expression pattern of ZNF281 correlated well with the
      expression of beta-CATENIN during differentiation and in the gain/loss-of
      function study in hMSCs. The binding of ZNF281 to the promoter region of beta
      CATENIN was observed using a chromatin immunoprecipitation (ChIP) assay. In
      conclusion, we propose that ZNF281 plays an important role in the maintenance and
      osteogenic differentiation of stem cells via the transcriptional regulation of
      genes including beta-CATENIN.

PMID- 22963692
TI  - The birth of a collaborative model: obstetricians, midwives, and family
      physicians.
AB  - In the United States, the challenges of maternity care include provider
      workforce, cost containment, and equal access to quality care. This article
      describes a collaborative model of care involving midwives, family physicians,
      and obstetricians at the Boston Medical Center, which serves a low-income
      multicultural population. Leadership investment in a collaborative model of care
      from the Department of Obstetrics and Gynecology, Section of Midwifery, and the
      Department of Family Medicine created a culture of safety and commitment to
      patient-centered care. Essential elements of the authors' successful model
      include a commitment to excellence in patient care, communication, and
      interdisciplinary education.

PMID- 22963691
TI  - Combination of small size and carboxyl functionalisation causes cytotoxicity of
      short carbon nanotubes.
AB  - The use of carbon nanotubes (CNTs) could improve medical diagnosis and treatment
      provided they show no adverse effects in the organism. In this study, short CNTs
      with different diameters with and without carboxyl surface functionalisation were
      assessed. After physicochemical characterisation, cytotoxicity in phagocytic and
      non-phagocytic cells was determined. The role of oxidative stress was evaluated
      according to the intracellular glutathione levels and protection by N-acetyl
      cysteine (NAC). In addition to this, the mode of cell death was also
      investigated. CNTs <8 nm acted more cytotoxic than CNTs >=20 nm and carboxylated
      CNTs more than pristine CNTs. Protection by NAC was maximal for large diameter
      pristine CNTs and minimal for small diameter carboxylated CNTs. Thin (<8 nm) CNTs
      acted mainly by disruption of membrane integrity and CNTs with larger diameter
      induced mainly apoptotic changes. It is concluded that cytotoxicity of small
      carboxylated CNTs occurs by necrosis and cannot be prevented by antioxidants.

PMID- 22963693
TI  - Midwifery and obstetrics: twenty years of collaborative academic practice.
AB  - This review describes a collaborative educational practice model partnering
      midwifery and obstetrics within a department of obstetrics and gynecology. For
      more than 20 years, the authors' model has demonstrated sustainability and
      influence on medical education. The focus is on resident education in obstetrics,
      using midwifery faculty as teachers in the obstetric and obstetric triage
      settings. This noncompetitive and integrated educational practice model has
      achieved sustainability and success using midwives in a collaborative approach to
      medical education. The continuing collaboration and innovation within medical and
      resident education are important elements for the future of collaborative
      practice.

PMID- 22963694
TI  - Description of a successful collaborative birth center practice among midwives
      and an obstetrician.
AB  - Collaboration among professional groups is essential for safe and efficient
      health care. Midwifery care is optimized when allowed to function independently
      within an integrated health care system of support to address complications
      should they arise. A formal process for collaboration facilitates a smooth,
      expedient flow of information and decision making in a time of need, maximizing
      safety and efficiency. This article describes a successful collaborative model
      among four midwives and one obstetrician that addresses the impending maternity
      health care provider shortage, the needs of vulnerable populations, and cost
      efficiency through appropriate use of technology and choice of health care
      provider.

PMID- 22963695
TI  - Midwives and obstetrician-gynecologists collaborating for Native American women's
      health.
AB  - Certified Nurse-Midwives (CNMs) and Obstetrician-Gynecologists (OBGs) have a long
      history of successful collaborative practice serving Native American women from
      the 1960s. CNMs provide holistic, patient-centered care focusing on normal
      pregnancy and childbirth. OBGs support CNMs with consultation services focusing
      on complications during pregnancy and specialty gynecology care. Collaborative
      care in Indian Health Service and Tribal sites optimizes maternity care in a
      supportive environment, achieving excellent outcomes including low rates of
      cesarean deliveries and high rates of successful vaginal birth after cesarean.

PMID- 22963696
TI  - A successful model of collaborative practice in a university-based maternity care
      setting.
AB  - When building an integrated practice, the ability of each team member to work
      comfortably with other professionals is key. Midwives need to understand
      departmental expectations for participation in resident/student education, be
      willing to provide midwifery care in a high-acuity setting with limited
      opportunities for low-intervention care, and understand expectations for clinical
      leadership. Physicians need to build on the group expectation of mutual respect
      and best use of each group member. Confusion about midwifery and physician roles
      in maternity care still exists.

PMID- 22963697
TI  - Working toward a common goal: a collaborative obstetrics and gynecology practice.
AB  - Health care reform in the United States will continue to necessitate creativity
      in the organization and staffing of health care models. The Department of
      Obstetrics and Gynecology at Bronx-Lebanon Hospital Center has expanded its staff
      by placing midwives as primary providers for most routine care and much of the
      specialty care offered within the department. Midwives and attending physicians
      work collaboratively in outpatient specialty clinics. Inpatient care is provided
      by a team of midwives, residents, and attending physicians. This model of care is
      easily replicated, and has resulted in improvements in clinical practice and
      increased patient and personnel satisfaction.

PMID- 22963698
TI  - Collaborative maternity care: three decades of success at Dartmouth-Hitchcock
      Medical Center.
AB  - This article describes the development of our collaborative practice, discusses
      the barriers and challenges presented by the current health care environment, and
      identifies factors that would encourage the initiation and strengthening of a
      successful collaborative model in similar settings. Successful collaborative
      practice is more than just a practice model, or a set of items that, once checked
      off, will guarantee success. It is a process that is inextricably linked to the
      focus and dedication of all our clinicians to provide the best care possible for
      women.

PMID- 22963699
TI  - Collaborative practice model: Madigan Army Medical Center.
AB  - In 2007, Madigan Army Medical Center implemented a new maternity care delivery
      model, integrating obstetricians and certified nurse-midwives (CNMs) in a
      collaborative practice. The change was driven by multiple factors, including
      patient preference, changes in the resident workweek, and low provider
      satisfaction. This article describes the elements of successful collaboration,
      including the structure, effective teamwork principles, role of the CNM in
      resident education, and preliminary data on mode of delivery, the number of CNM
      supervised resident births, and procedures, such as episiotomy and epidural use.

PMID- 22963700
TI  - Interprofessional collaborative practice in obstetrics and midwifery.
AB  - As the health care system transforms to accommodate an increased need for primary
      care services and more patients, new models of health care delivery are needed
      that can provide quality health care services efficiently. An integrated
      collaborative practice of certified nurse-midwives, obstetrician-gynecologists,
      and perinatologists is best suited to meet the rapidly changing needs of the
      maternity health care delivery system. This article reviews the literature on
      interprofessional collaborative practice and describes the structure, function,
      and essential elements of successful collaboration in health care.

PMID- 22963701
TI  - Essential components of successful collaborative maternity care models: the ACOG
      ACNM project.
AB  - The American College of Obstetricians and Gynecologists (ACOG) and the American
      College of Nurse-Midwives (ACNM) asked ACNM member midwives and ACOG Fellows with
      successful and sustainable collaborative practices between obstetricians and
      midwives to describe their care models in jointly written articles. This review
      analyzes 12 of the 60 articles submitted. Five main themes were identified:
      impetus for new collaboration, basic foundations of collaborative care,
      commitment to successful partnership, care integration, and health professions
      education in an interprofessional practice environment. The analysis provides
      evidence of the extent to which committed clinicians are working together to
      provide excellent, women-centered maternity care.

PMID- 22963702
TI  - Collaboration in maternity care: possibilities and challenges.
AB  - The United States is about to face a maternity workforce crisis in the next
      decade because the number of medical students choosing obstetrics and gynecology
      is stagnant, the number of patients requiring care is increasing and many in the
      current workforce of obstetricians/gynecologists and midwives are ready to
      retire. There are not enough maternity providers to meet the future needs of
      women. Creative strategies must be explored to address these concerns.
      Collaborative practice among different types of maternity providers requires
      commitment, interpersonal skills, and teamwork. This article explores these
      issues and provides practical tips and a case study of the process in action
      between the American College of Obstetricians and Gynecologists and the American
      College of Nurse-Midwives.

PMID- 22963703
TI  - The long and winding road to effective collaboration.

PMID- 22963704
TI  - Effective collaboration.

PMID- 22963705
TI  - Involvement of lipid rafts in multiple signal transductions mediated by two
      isoforms of thromboxane A2 receptor: dependency on receptor isoforms and
      downstream signaling types.
AB  - Lipid rafts, microdomains in the plasma membrane, are known to be involved in G
      protein-coupled receptor signal transduction; however, their involvement in
      thromboxane A(2) receptor (TP) signaling remains to be clarified. We examined
      whether two isoforms of TP, TPalpha and TPbeta, utilize lipid rafts for multiple
      G protein signal transduction. Sucrose density gradient centrifugation followed
      by western blotting of HEK cells expressing TPalpha or TPbeta revealed the
      localization of both TPalpha and TPbeta in lipid rafts. Furthermore, methyl-beta
      cyclodextrin, which destroys lipid raft structure by depleting cholesterol,
      influenced G protein signaling elicited by TPalpha and TPbeta to varying degrees.
      Phosphatidylinositol hydrolysis and cAMP accumulation induced by TPalpha or
      TPbeta stimulation was markedly inhibited by methyl-beta-cyclodextrin. In
      contrast, treatment with methyl-beta-cyclodextrin partially inhibited RhoA
      activation induced by TPalpha stimulation, but failed to affect TPbeta
      stimulation. Furthermore, the inhibitory action of methyl-beta-cyclodextrin on
      cAMP accumulation was specific to TPalpha and TPbeta, because methyl-beta
      cyclodextrin enhanced forskolin and beta-adrenergic stimulation-induced cAMP
      accumulation. These results indicate that TP isoforms depend on lipid rafts
      during G(q) and G(s) signaling, while G(13) signaling mediated by TP isoforms
      does not. Moreover, TPalpha seems to be more lipid raft-dependent with respect to
      RhoA activation than TPbeta. These results indicate that the two isoforms of the
      TP mediate multiple signal transductions with varying degrees of lipid raft
      dependency. Moreover, our results provide a deeper understanding of the function
      of lipid rafts in G protein signaling and the physiological meaning of TP
      isoforms.

PMID- 22963706
TI  - Zero-order release profile of metoclopramide hydrochloride sublingual tablet
      formulation.
AB  - This report describes zero-order approximation for metoclopramide hydrochloride
      sublingual tablet formulation. Effects of type and concentration of excipients on
      release were investigated. Study revealed that highest rate of dissolution was
      attained with crosspovidone and decreased in the order crosspovidone > sodium
      starch glycolate > ac-di-sol. All formulations demonstrated flush release, except
      the one containing 10% crosspovidone where a lag time of 0.5 min. was depicted.
      Increasing the concentration of crosspovidone from 5 to 10% gave the same half
      life, whereas kinetics of release changed to zero order. Differential scanning
      colorimetry and infrared spectroscopy did not reveal any sign of physical or
      chemical interaction between drug and crosspovidone. In order to study the
      alignment of polymeric network inside tablet matrix, scanning electron microscopy
      was performed on the tablet and its cross-section. Matrix with 10% crosspovidone
      showed higher density of interconnections extending to the interior of core
      enabling fast and constant release. Hence physicochemical characteristics of
      crosspovidone could be tailored by varying its concentration, in a way that
      provided a porous matrix with tight arrangement of polymeric chains, resembling
      to an assemblage of cylinders with constant apertures, from which zero-order
      release was approached. 

PMID- 22963707
TI  - Ceramide, cerebroside and triterpenoid saponin from the bark of aerial roots of
      Ficus elastica (Moraceae).
AB  - Three compounds, ficusamide (1), ficusoside (2) and elasticoside (3), were
      isolated from the bark of aerial roots of Ficus elastica (Moraceae), together
      with nine known compounds, including four triterpenes, three steroids and two
      aliphatic linear alcohols. The chemical structures of the three compounds were
      established by extensive 1D and 2D NMR spectroscopy, mass spectrometry and by
      comparison with published data. The growth inhibitory effect of the crude extract
      and isolated compounds was evaluated against several microorganisms and fungi.
      The cytotoxicity against human cancer cell lines was also assessed. Ficusamide
      (1) displayed a moderate in vitro growth inhibitory activity against the human
      A549 lung cancer cell line and a strong activity against Staphylococcus
      saprophyticus, while elasticoside (3) showed a potent activity on Enterococcus
      faecalis.

PMID- 22963708
TI  - Preamble: 'evidence in action: the Laboratory Medicine Best Practice initiative'.

PMID- 22963709
TI  - Evidence in action; commentary.

PMID- 22963710
TI  - Ivermectin and moxidectin resistance characterization by larval migration
      inhibition test in field isolates of Cooperia spp. in beef cattle, Mato Grosso do
      Sul, Brazil.
AB  - Ivermectin (IVM) resistance of Cooperia spp. in cattle has become an increasing
      and global problem. The early detection of anthelmintic resistance (AR) is
      important to propose strategies to slow down the development of resistance and
      requires sensitive, reliable, economic high-throughput and practical tests. The
      purpose of the present study was to apply a larval migration inhibition test
      (LMIT) for evaluating IVM and MOX efficacy against well-characterized field
      isolates of Cooperia spp. infecting cattle in Brazil. Eight isolates were used
      for IVM and seven for MOX. The following EC50 values of IVM were observed for the
      isolates: susceptible, 1.16 etamol; Nova Alvorada do Sul I, 4.09 etamol
      (RF=3.52); Campo Grande BNA, 3.57 etamol (RF=3.07); Campo Grande TBR, 4.09 etamol
      (RF=3,52); Nova Alvorada do Sul II, 2.50 etamol (RF=2.15); Bandeirantes, 11.35
      etamol (RF=9.78); Campo Grande II, 6.03 etamol (RF=5.20); and Porto Mortinho,
      8.63 etamol (RF=7.44). For MOX, the following EC50 values were observed:
      susceptible, 0.75 etamol; Campo Grande BNA, 0.93 etamol (RF=1.24); Campo Grande
      TBR, 0.36 etamol (RF=0.48); Nova Alvorada do Sul II, 2.57 etamol (RF=3.42);
      Bandeirantes, 1.43 etamol (RF=1.90); Campo Grande II, 1.08 etamol (RF=1.44); and
      Porto Mortinho, 0.49 etamol (RF=0.65). The LMIT used in the present study can be
      a useful tool for in vitro evaluation of IVM, but not of MOX. However, such
      methodology cannot be used in large-scale studies yet. The isolates of Cooperia
      spp. showed various degrees of resistance to IVM, though remaining susceptible to
      MOX.

PMID- 22963711
TI  - D-dimer deposits in lungs and kidneys suggest its use as a marker in the clinical
      workup of dogs with heartworm (Dirofilaria immitis) disease.
AB  - It has been reported that dogs with heartworm disease (Dirofilaria immitis) show
      increased plasma levels of D-dimer, a fibrin degradation product present in the
      blood after a blood clot is degraded by fibrinolysis. In the present study the
      authors show that, in dogs with both experimental and natural infections with D.
      immitis, D-dimer deposits in lungs and kidneys are associated with pulmonary
      thromboembolism and microfilariemic status, as well as there was a clear
      association between increased plasma values of D-dimer and positive staining in
      immunohistochemistry. Results suggest that the monitoring of D-dimer levels in
      infected dogs could be useful in evaluating the presence of pulmonary
      thromboembolism in the lungs and that microfilariae may induce microthrombosis in
      kidneys, thus contributing to renal pathology.

PMID- 22963712
TI  - Identity and public health potential of Cryptosporidium spp. in water buffalo
      calves in Egypt.
AB  - Little is known about the diversity and public health significance of
      Cryptosporidium species in water buffaloes. In this study, we examined the
      distribution of Cryptosporidium spp. in water buffalo calves in Egypt. Rectal
      fecal specimens from 179 calves and 359 adults were screened microscopically for
      Cryptosporidium oocysts using modified Ziehl-Neelsen stain. Cryptosporidium spp.
      in 17 microscopy-positive specimens from calves were genotyped by DNA sequence
      analysis of the small-subunit rRNA gene, and Cryptosporidium parvum was subtyped
      by sequence analysis of the 60 kDa glycoprotein gene. Cryptosporidium ryanae was
      found in 10 specimens and C. parvum in 7 specimens, with the former belonging to
      the newly identified C. ryanae buffalo variant and the latter belonging to the
      subtypes IIdA20G1 (in 5 specimens) and IIaA15G1R1 (in 2 specimens). The
      prevailing occurrence of C. ryanae and the subtype family IId of C. parvum and
      the absence of C. bovis and C. andersoni represent some features of
      Cryptosporidium transmission in water buffaloes in Egypt.

PMID- 22963713
TI  - Chemical composition of silage residues sustaining the larval development of the
      Culicoides obsoletus/Culicoides scoticus species (Diptera: Ceratopogonidae).
AB  - Culicoides (Diptera: Ceratopogonidae) are biological vectors of bluetongue virus
      (BTV). Bluetongue is a viral disease that affects domestic and wild ruminants.
      Since its recent emergence in northern Europe, this disease has caused
      considerable economic losses to the sheep and cattle industry. The biotopes, and
      more particularly the chemical characteristics which are suitable for larval
      development of the main vector species, are still relatively unknown. This study
      shows that the larvae of biting midges belonging to the species Culicoides
      obsoletus and Culicoides scoticus are able to breed in different types of silage
      residue (maize, grass, sugar beet pulp and their combinations). The chemical
      composition of substrates strongly influences the presence of the immature stages
      of these biting midges. Higher lignin and insoluble fibre contents seem to favour
      their presence and could play the role of a physical support for semi-aquatic
      larvae. In contrast, higher concentrations of magnesium and calcium are
      negatively correlated with the presence of these two species. These data will
      help to locate and monitor the breeding sites of these species and could
      contribute to the control of these insects on farms.

PMID- 22963714
TI  - Platynosomum fastosum-induced cholangiocarcinomas in cats.
AB  - Platynosomum fastosum is a feline biliary tract trematode that generally causes
      asymptomatic infections. In the early 1980s in Brazil, P. fastosum was associated
      with cholangiocarcinomas, but this finding was not confirmed in the various
      publications on the parasite during the last 30 years. This study aims to report
      three cases of cholangiocarcinomas in cats associated with the presence of P.
      fastosum. From 2000 to 2011, in the Veterinary Hospital of the Federal University
      of Campina Grande in northeast Brazil, 348 cats were necropsied, 11 of which
      (3.16%) were parasitized by P. fastosum. Three cases that resulted in death were
      associated with cholangiocarcinomas that were found to be associated with P.
      fastosum. Histologically, the tumors consisted of acini composed of cells with
      pleomorphic nuclei, loose chromatin, evident nucleoli and lightly eosinophilic
      cytoplasm. Metastases were observed in two cases. The first case involved
      metastases to the lungs, kidneys, ovary and peritoneum, and in the second case,
      the lymph nodes, kidneys, heart and encephalon were involved. The other 8 cats
      died from other causes, and the parasite was an incidental finding. In those
      cases, the histologic lesions were nonsuppurative cholangiohepatitis and
      periductal fibrosis with P. fastosum present. Six animals also showed pre
      neoplastic changes (hyperplasia and dysplasia) of the biliary duct epithelium.
      The study concluded that, as observed in other human biliary tract trematodes, P.
      fastosum causes cholangiocarcinomas in the liver of cats.

PMID- 22963715
TI  - Oxidative stress responses in blood and gills of Carassius auratus exposed to the
      mancozeb-containing carbamate fungicide Tattoo.
AB  - Intensive use of pesticides, particularly dithiocarbamates, in agriculture often
      leads to contamination of freshwater ecosystems. To our knowledge, the mechanisms
      of toxicity to fish by the carbamate fungicide Tattoo that contains mancozeb
      [ethylenebis(dithiocarbamate)] have not been studied. The present study aimed to
      evaluate the effects of Tattoo on goldfish gills and blood, tissues that would
      have close early contact with the pollutant. Exposure of goldfish Carassius
      auratus to 3, 5 or 10mgL(-1) of Tattoo for 96h resulted in moderate lymphopenia
      (by 8 percent) with a concomitant increase in both stab (by 66-88 percent) and
      segmented (by 166 percent) neutrophils. An increase in the content of protein
      carbonyl groups in blood (by 137-184 percent) together with decreased levels of
      protein thiols (by 23 percent) and an enhancement of lipid peroxide
      concentrations (by 29 percent) in gills after exposure to 10mgL(-1) of Tattoo
      demonstrated the induction of mild oxidative stress in response to Tattoo
      exposure. At the same time, the activities of selected antioxidant enzymes were
      enhanced in gills: superoxide dismutase by 18-25 percent and catalase by 27
      percent. A 34 percent increment in low molecular mass thiol concentrations
      (mainly represented by glutathione) also occurred in gills and could be related
      to increased activity (by 13-30 percent) of glucose-6-phosphate dehydrogenase.
      The results indicate that Tattoo exposure perturbs free radical processes, i.e.
      induces mild oxidative stress and enhances the activity of certain antioxidant
      and associated enzymes in goldfish gills. It is clear that goldfish respond to
      the presence of waterborne pesticide by adjusting antioxidant defenses through
      upregulation of activities of antioxidant and associated enzymes.

PMID- 22963716
TI  - The effect of dry cow antibiotic with and without an internal teat sealant on
      udder health during the first 100 d of lactation: a field study with matched
      pairs.
AB  - The objective of this field study was to compare the udder health status as well
      as the clinical mastitis rate during the first 100 d of lactation in cows that
      received long-acting dry cow antibiotic alone (group AB) or in combination with
      an internal teat sealant (group AB + OS). The study was conducted during a 9
      month period and included 136 Holstein cows from 12 dairy farms in Hessia,
      Germany. Between days 1 and 5 after calving a California mastitis test (CMT) was
      performed. Milk-samples were collected for bacteriological culture before drying
      off, between days 6 and 14 and days 35 and 56 of lactation. Additionally the cows
      were monitored for the occurrence of clinical mastitis events until 100 d post
      partum. Within the 12 herds cow-pairs were formed on the basis of age, milk yield
      and SCC. A cow-pair consisted of one cow from group AB and one cow from group AB
      + OS. For statistical analysis within every cow-pair one quarter that has been
      dried off with internal teat sealant and dry cow antibiotic (group AB + OS) was
      compared with one quarter that has been dried off with dry cow antibiotic (group
      AB) alone. As criterion for the matching process of udder quarters the
      cytobacteriological udder health status before drying off was used. A total of
      544 quarters (136 cows) were used in this analysis. In the first 5 d after
      calving, group AB had significantly more quarters with a positive CMT reaction
      than group AB + OS (85 vs. 57; P <0.001), and in the first 100 d of lactation,
      group AB had more quarters with clinical mastitis than group AB + OS (25 vs. 15;
      P = 0.03). In the time periods 6-14 and 35-56 d of lactation, there were fewer
      quarters in group AB + OS populated with Corynebacterium spp. (days 6-14, P =
      0.05; days 35-56, P = 0.02) and aesculin-positive streptococci (days 35-56, P =
      0.02). The internal teat sealant was a promising tool for the prevention of new
      intramammary infections (IMI) of dry cows with environmental udder pathogens as
      expressed during early lactation.

PMID- 22963718
TI  - [Evidence on the utility of hemodynamic monitorization in the critical patient].
AB  - Hemodynamic monitoring is a tool of great value for the assessment of critically
      ill patients. It can not only detect and determine the source of hemodynamic
      instability, but also guide the choice of appropriate treatment and further
      evaluate its effectiveness. However, monitoring per se is not a therapeutic tool
      and its use in the absence of a well-defined objective, need not affect patient
      outcome. To improve outcome, hemodynamic monitoring necessarily must be coupled
      to a treatment protocol that has effectively been shown to improve outcome.
      Accordingly, the usefulness of monitoring systems should be evaluated not only on
      the basis of the accuracy and reliability of their measurements, but also on the
      ability to positively affect patient outcome. In this regard, many of the
      arguments against the use of hemodynamic monitoring are a consequence of non
      protocolized use and of application not directed towards specific hemodynamic
      objectives of proven benefit for the patient.

PMID- 22963717
TI  - The interaction between ER and NFkappaB in resistance to endocrine therapy.
AB  - Endocrine therapy is a commonly used treatment for estrogen receptor (ER)
      positive breast cancer. Although endocrine therapy has a favorable outcome in
      many patients, development of resistance is common. Recent studies have shown
      that NFkappaB, a transcription factor regulating a wide variety of cellular
      processes, might play a role in the development of endocrine resistance. The
      precise interaction between ER and NFkappaB and how this contributes to the
      attenuated responsiveness of ER-positive breast cancer cells to hormonal
      treatment remains unclear. This review provides an overview of the mechanisms of
      action for both transcription factors and focuses on the current knowledge
      explaining how ER and NFkappaB affect each other's activity and how this cross
      talk might contribute to the development of an endocrine resistance phenotype in
      breast cancer cells. 

PMID- 22963719
TI  - Risky alcohol use among reproductive-age men, not women, in Mae La refugee camp,
      Thailand, 2009.
AB  - BACKGROUND: Globally, alcohol use contributes to close to 4% of all deaths and
      is a leading cause of ill health and premature death among men of reproductive
      age. Problem alcohol use is an unaddressed public health issue among populations
      displaced by conflict. Assessing the magnitude of the problem and identifying
      affected groups and risk behaviours is difficult in mobile and unstable
      populations. METHODS: From 15-28 December 2009 we conducted a simple rapid
      screening test of risky alcohol use using the single item modified Short
      Assessment Screening Questionnaire (mSASQ) by all women currently enrolled in the
      antenatal care clinic in Mae La refugee camp, a long standing displaced setting
      on the Thai Burma border. Women self- reported and gave a secondary report of
      their male partners. Gender differences in alcohol use were further explored in
      semi-structured interviews with camp residents on attitudes, behaviours, and
      beliefs regarding alcohol and analysed thematically. RESULTS: Of 636 women
      screened in the antenatal clinic, almost none (0.2%, 95CI 0.0-0.9%) reported
      risky alcohol use prior to pregnancy, whereas around a quarter (24.4%, 95CI 21.2
      27.9%) reported risky alcohol use by their male partners. Interviews with 97 camp
      residents described strong social controls against women's alcohol use and men's
      drinking to intoxication, despite a dominant perception that the social context
      of life in displacement promoted alcohol use and that controls are loosening.
      CONCLUSIONS: As a stigmatised behaviour, alcohol use is difficult to assess,
      particularly in the context of highly mobile adult male populations: the simple
      assessment methods here show that it is feasible to obtain adequate data for the
      purposes of intervention design. The data suggest that risky drinking is common
      and normalised among men, but that the population may have been partially
      protected from rapid rises in problem alcohol use observed in nation-wide data
      from Thailand. The changing social context contains vulnerabilities that might
      promote problem alcohol use: further investigation, ongoing monitoring, and
      development of targeted interventions are warranted.

PMID- 22963720
TI  - ABO blood groups and abdominal aortic aneurysm.
AB  - Earlier studies have indicated an association between blood group non-O and
      atherosclerosis related vascular diseases. Abdominal aortic aneurysm (AAA) is
      traditionally regarded as a consequence of atherosclerosis. The aim of the
      present study was to investigate the association between ABO blood groups and AAA
      with special regard to a relation to AAA rupture. Prospectively, 504 patients
      operated on for AAA were investigated. Patients operated on for AAA have similar
      ABO blood group distributions as a population based control group. Furthermore,
      there was no significant difference in distribution of ABO blood group between
      patients operated on for ruptured AAA (n=174) and non-ruptured AAA (n=330). In
      conclusion, this study fails to demonstrate an association between ABO blood
      groups and AAA.

PMID- 22963721
TI  - Fusarium infection of maize and maize-based products and exposure of a rural
      population to fumonisin B1 in Limpopo Province, South Africa.
AB  - Fusarium species (spp.) and fumonisin B1 (FB1) contaminations were monitored in
      maize and porridge consumed by a rural population of Limpopo Province, South
      Africa. Faecal samples were also analysed for FB1 as a means of estimating the
      degree of dietary exposure to this mycotoxin. In total, 142 samples of maize (n =
      54), porridge (47) and faeces (41) were screened for Fusarium spp. using a serial
      dilution technique followed by DNA sequencing, while FB1 was further screened and
      quantified by thin-layer chromatography (TLC) and high-performance liquid
      chromatography (HPLC), respectively. At least four species of Fusarium were
      identified, of which F. verticillioides was the most prevalent in all three
      sample types analysed. The contamination levels of FB1 were significantly higher
      in 87% of maize sampled (range = 101-53,863 ug kg-1) as compared with porridge
      (74% incidence rate; range = 0.2-20 ug kg-1) and faecal samples (100% incidence
      rate; range = 0.3-464 ug kg-1). Thus, it can be deduced that the level of human
      exposure to FB1 via the consumption of maize was high as several samples
      contained levels exceeding 1000 ug kg-1, which was strongly supported by the
      levels found in faecal samples. Further data revealed that a high proportion of
      FB1 is destroyed or removed by processing maize into porridge. As maize porridge
      is consumed as a staple, the low levels found provide a means to limit exposure
      to FB1. Levels of FB1 found in the faeces which were higher indicate that other
      foods contaminated with the toxin are also consumed.

PMID- 22963722
TI  - Locally weighted learning methods for predicting dose-dependent toxicity with
      application to the human maximum recommended daily dose.
AB  - Toxicological experiments in animals are carried out to determine the type and
      severity of any potential toxic effect associated with a new lead compound. The
      collected data are then used to extrapolate the effects on humans and determine
      initial dose regimens for clinical trials. The underlying assumption is that the
      severity of the toxic effects in animals is correlated with that in humans.
      However, there is a general lack of toxic correlations across species. Thus, it
      is more advantageous to predict the toxicological effects of a compound on humans
      directly from the human toxicological data of related compounds. However, many
      popular quantitative structure-activity relationship (QSAR) methods that build a
      single global model by fitting all training data appear inappropriate for
      predicting toxicological effects of structurally diverse compounds because the
      observed toxicological effects may originate from very different and mostly
      unknown molecular mechanisms. In this article, we demonstrate, via application to
      the human maximum recommended daily dose data that locally weighted learning
      methods, such as k-nearest neighbors, are well suited for predicting
      toxicological effects of structurally diverse compounds. We also show that a
      significant flaw of the k-nearest neighbor method is that it always uses a
      constant number of nearest neighbors in making prediction for a target compound,
      irrespective of whether the nearest neighbors are structurally similar enough to
      the target compound to ensure that they share the same mechanism of action. To
      remedy this flaw, we proposed and implemented a variable number nearest neighbor
      method. The advantages of the variable number nearest neighbor method over other
      QSAR methods include (1) allowing more reliable predictions to be achieved by
      applying a tighter molecular distance threshold and (2) automatic detection for
      when a prediction should not be made because the compound is outside the
      applicable domain.

PMID- 22963723
TI  - Primary pseudomyogenic haemangioendothelioma of bone.
AB  - AIMS: Pseudomyogenic haemangioendothelioma is a recently described vascular
      neoplasm that occurs most commonly in the soft tissue of distal extremities of
      young adults. Occurrence outside the somatic soft tissue has not been described
      thus far. We present here a unique case of pseudomyogenic haemangioendothelioma
      that arose in the long tubular bones of the lower extremity. METHODS AND RESULTS:
      The initial open biopsy was interpreted as a fibrous histiocytoma. However, the
      curettage specimen showed prominent epithelioid cytomorphology with a striking
      rhabdomyoblast-like appearance. By immunohistochemistry, the linear membranous
      staining of CD31 was highly suggestive of endothelial differentiation of the
      tumour cells. CONCLUSIONS: To the best of our knowledge, this case represents the
      first example of primary pseudomyogenic haemangioendothelioma of bone. Clinical
      and pathological correlation with application of immunohistochemistry is
      mandatory in establishing the correct diagnosis and excluding tumours with
      overlapping features.

PMID- 22963724
TI  - Development of (99m)Tc-EC-tyrosine for early detection of breast cancer tumor
      response to the anticancer drug melphalan.
AB  - RATIONALE AND OBJECTIVES: Radiolabeled tyrosine analogues that have been
      successfully used in tumor imaging accumulate in tumor cells via an upregulated L
      type amino acid transporter system. The anticancer drug melphalan is an L-type
      amino acid transporter substrate. Therefore, radiolabeled tyrosine analogues may
      have great potential in evaluating treatment responses to melphalan. In this
      study, a (99m)Tc-labeled tyrosine analogue, (99m)Tc tyrosine using N,N'-ethylene
      di-L-cysteine (EC) as a chelator, was developed and its potential for
      noninvasively assessing tumors' early response to melphalan determined. MATERIALS
      AND METHODS: EC-tyrosine was synthesized in a three-step procedure and labeled
      with (99m)Tc. To assess cellular uptake kinetics, the percentage uptake of
      (99m)Tc-EC-tyrosine in the rat breast cancer cell line 13762 was measured. Planar
      imaging was performed in rats with 13762 cell-derived tumors. To determine the
      transport mechanisms of (99m)Tc-EC-tyrosine, a competitive inhibition study using
      L-tyrosine as an inhibitor was performed in vitro and in vivo. To assess tumors'
      response to melphalan, tumor-bearing rats were treated with different doses of
      melphalan, and planar imaging was performed 0 and 3 days after treatment.
      Immunohistochemical analyses were conducted to determine expressions of L-type
      amino acid transporter 1 and cellular proliferation marker Ki-67. RESULTS: L
      tyrosine significantly inhibited (99m)Tc-EC-tyrosine uptake in vitro and in vivo.
      Tumor volume decreased in a dose-dependent manner with melphalan, and
      tumor/muscle ratios of (99m)Tc-EC-tyrosine were significantly reduced in treated
      groups. Immunohistochemical data indicated that about 70% of tumor cells in the
      melphalan-treated groups underwent apoptosis, and the changes in tumor/muscle
      ratios reflected the decreased percentage of viable cells in treated tumors.
      CONCLUSIONS: These findings suggest that (99m)Tc-EC-tyrosine has great potential
      for monitoring tumor response to melphalan in breast tumor-bearing rats.

PMID- 22963725
TI  - Reference curves for the aortic area by age.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to establish reference curves
      and formulas for aortic cross-sectional area in patients from infancy to young
      adulthood. MATERIALS AND METHODS: Patients (aged 2 days to 18.1 years) who
      underwent electrocardiographically gated cardiac computed tomography between May
      2004 and December 2011 were retrospectively examined. These patients were further
      divided into a group of normal controls (without aortic disease) and a group with
      coarctation of aorta. In the group of normal controls, the cross-sectional area
      of the aorta was measured at six locations: the sinotubular junction, distal
      ascending aorta, proximal arch, distal arch, aortic isthmus, and descending aorta
      (DAO). Interobserver and intraobserver variability, gender differences, the
      relationship between aortic cross-sectional areas and age, and the ratio to the
      DAO were also examined. The area ratio to the DAO was also examined in the group
      with coarctation of the aorta. RESULTS: A total of 65 patients and 365 measurable
      aortic segments were included in the analysis (55 normal controls and 10 patients
      with coarctation of aorta). Interobserver and intraobserver variability was
      limited (aside from measurements of the sinotubular junction). There were no
      gender differences in age and the cross-sectional areas of the different aortic
      segments. In the group of normal controls, the cross-sectional area of each
      aortic segment was highly correlated with age (all >0.90, P < .001). The
      reference curves and formulas for aortic cross-sectional area by age were also
      determined for further clinical use. In the normal controls, the <95% confidence
      intervals of the ratios of aortic isthmus to DAO, distal arch to DAO, and
      proximal arch to DAO were approximately 0.6, 0.8, and 1.0, respectively. In
      addition, in the group with coarctation, all area ratios of aortic isthmus to DAO
      were <0.6, which was significantly different from the group of normal controls (P
      < .001). The area ratios of distal arch to DAO and proximal arch to DAO were also
      significantly different between two groups (P < .001 for both). CONCLUSIONS:
      Measurement of aortic area was reproducible. The established reference curves and
      formulas and minimal area ratios were convenient for further clinical use.

PMID- 22963726
TI  - Motion correction of multi-b-value diffusion-weighted imaging in the liver.
AB  - RATIONALE AND OBJECTIVES: Motion artifacts are a significant source of error in
      the acquisition and quantification of parameters from multi-b-value diffusion
      weighted imaging (DWI). The objective of this article is to present a reliable
      method to reduce motion-related artifacts during free-breathing at higher b
      values when signal levels are low. MATERIALS AND METHODS: Twelve patients
      referred for magnetic resonance imaging of the liver underwent a clinical
      magnetic resonance imaging examination of the abdominal region that included DWI.
      Conventional single-shot spin-echo echo planar imaging acquisitions of the liver
      during free breathing were repeated in a "time-resolved" manner during a single
      acquisition to obtain data for multi-b-value analysis, alternating between low
      and high b-values. Image registration using a normalized mutual information
      similarity measure was used to correct for spatial misalignment of diffusion
      weighted volumes caused by motion. Registration error was estimated indirectly by
      comparing the normalized root-mean-square error (NRMSE) values of data fitted to
      the biexponential intra-voxel incoherent motion model before and after motion
      correction. Regions of interest (ROIs) were selected in the liver close to the
      surface of the liver and close to internal structures such as large bile ducts
      and blood vessels. RESULTS: For the 12 patient datasets, the mean NRMSE value for
      the motion-corrected ROIs (0.38 +/- 0.16) was significantly lower than the mean
      NRMSE values for the non-motion-corrected ROIs (0.41 +/- 0.13) (P < .05). In
      cases where there was substantial respiratory motion during the acquisition,
      visual inspection verified that the algorithm markedly improved alignment of the
      liver contours between frames. CONCLUSIONS: The proposed method addresses motion
      related artifacts to increase robustness in multi-b-value acquisitions.

PMID- 22963727
TI  - Positive bias is a defining characteristic of aging to the same extent as
      declining performance.
AB  - The aim of this study was to analyze whether one of the supposed gains of aging-
      positive bias--discriminates between young and older participants to the same
      extent as some of the losses in cognitive performance--recall and source
      monitoring--that come with age. Two age groups (N = 120)--young (M = 22.08, SD =
      3.30) and older (M = 72.78, SD = 6.57)--carried out three tasks with varying
      levels of difficulty that included recall, recognition, and source monitoring
      using pictures, faces, and personal descriptors exchanged in a conversation as
      stimuli. The results of the discriminant analysis performed on 20 dependent
      variables indicated that six of them were key in discriminating between young and
      older participants. Younger participants outperformed older participants in
      recalling pictures, and in recognizing the descriptors exchanged in a
      conversation, as well as in monitoring their source. Just as important in
      discriminating between the two groups were the ability to recognize previously
      seen pictures, the likability rating they produced, and the recognition of faces
      with positive expressions--all superior in older participants. Thus, variables
      related to a positive bias--likability ratings and recognition of positive
      expressions--characterize the differences as a function of age as well as
      variables related to cognitive performance, such as recall and source monitoring.
      In addition, the likability ratings evoked by both pictures and faces were also
      significantly higher in the older participants with better cognitive performance
      than in those who performed poorly. This effect was not present in younger
      participants. The results are interpreted within the framework of socioemotional
      selectivity theory as evidence for a positive bias in old age. The connection
      between a positive bias and the maintenance of cognitive performance is also
      discussed.

PMID- 22963728
TI  - Isolation and biochemical, functional and structural characterization of a novel
      L-amino acid oxidase from Lachesis muta snake venom.
AB  - The aim of this study was the isolation of the LAAO from Lachesis muta venom
      (LmLAAO) and its biochemical, functional and structural characterization. Two
      different purification protocols were developed and both provided highly
      homogeneous and active LmLAAO. It is a homodimeric enzyme with molar mass around
      120 kDa under non-reducing conditions, 60 kDa under reducing conditions in SDS
      PAGE and 60852 Da by mass spectrometry. Forty amino acid residues were directly
      sequenced from LmLAAO and its complete cDNA was identified and characterized from
      an Expressed Sequence Tags data bank obtained from a venom gland. A model based
      on sequence homology was manually built in order to predict its three-dimensional
      structure. LmLAAO showed a catalytic preference for hydrophobic amino acids (K(m)
      of 0.97 mmol/L with Leu). A mild myonecrosis was observed histologically in mice
      after injection of 100 MUg of LmLAAO and confirmed by a 15-fold increase in CK
      activity. LmLAAO induced cytotoxicity on AGS cell line (gastric adenocarcinoma,
      IC50: 22.7 MUg/mL) and on MCF-7 cell line (breast adenocarcinoma, IC50:1.41
      MUg/mL). It presents antiparasitic activity on Leishmania brasiliensis (IC50:
      2.22 MUg/mL), but Trypanosoma cruzi was resistant to LmLAAO. In conclusion,
      LmLAAO showed low systemic toxicity but important in vitro pharmacological
      actions.

PMID- 22963729
TI  - Pygmy rattlesnake envenomation treated with Crotalidae Polyvalent Immune Fab
      Antivenom.
AB  - Documented envenomations by the pygmy rattlesnake (Sistrurus miliarius barbouri)
      are rare. While there have been no documented fatalities, several older case
      reports describe significant morbidity. We describe the first known case of pygmy
      rattlesnake envenomation that was treated with Crotalidae Polyvalent Immune Fab
      Antivenom (CroFab(r)). CASE: A 28-year-old man with no significant past medical
      history presented after being envenomated on the right hand by his friend's pet
      pygmy rattlesnake. He developed swelling and pain in his hand and forearm. He
      responded well to a ten vial loading dose and a 18 h maintenance protocol of
      CroFab and was discharged the following day without developing any hematological
      or electrolyte derangements. CONCLUSION: This is the first documented use of
      CroFab for S. m. barbouri envenomation. The outcome of this case suggests that
      CroFab is a safe treatment modality in this setting.

PMID- 22963730
TI  - AG490 improves the survival of human myoblasts in vitro and in vivo.
AB  - Cell therapies consist in transplanting healthy cells into a disabled tissue with
      the goal to repopulate it and restore its function at least partially. In
      muscular diseases, most of the time, myoblasts are chosen for their expansion
      capacity in culture. Nevertheless, cell transplantation  has limitations, among
      them, death of the transplanted cells, during the days following the graft. One
      possibility to counteract this problem is to enhance the proliferation of the
      transplanted myoblasts before their fusion with the existing muscle fibers. AG490
      is a specific inhibitor of  janus tyrosine kinase 2 (JAK2). The hypothesis is to
      block myoblast differentiation with AG490, thus permitting their proliferation.
      The inhibition of myoblast fusion by AG490 was confirmed in this study by gene
      expression and with a myosin heavy chain staining (MyHC). Moreover, cell survival
      was estimated by flow cytometry. AG490 was found to protect myoblasts in vitro
      from apoptosis induced by H(2)O(2) or by preventing attachment of cells to their
      substrate. Finally, in an in vivo model of muscle regeneration, when AG490 was
      coinjected with the myoblasts their  survival was increased by 45% at 5 days
      after their transplantation.

PMID- 22963731
TI  - Effect of intranasal arginine vasopressin on human headache.
AB  - Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches
      the central nervous system from systemic blood circulation with a difficulty
      because of the blood-brain barrier (BBB). The interest has been expressed in the
      use of the nasal route for delivery of AVP to the brain directly, exploiting the
      olfactory pathway. Our previous study has demonstrated that AVP in the brain
      rather than the spinal cord and blood circulation plays an important role in rat
      pain modulation. For understanding the role of AVP on pain modulation in human,
      the communication tried to investigate the effect of intranasal AVP on human
      headache. The results showed that (1) AVP concentration in both plasma and
      cerebrospinal fluid (CSF) increased significantly in headache patients, who
      related with the headache level; (2) there was a positive relationship between
      plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP
      could relieve the human headache in a dose-dependent manner. The data suggested
      that intranasal AVP, which was delivered to the brain through olfactory region,
      could treat human headache and AVP might be a potential drug of pain relief by
      intranasal administration.

PMID- 22963732
TI  - A critical evaluation of diagnostic methods used to identify dairy cows with
      acute post-partum metritis in the current literature.
AB  - The overall objective of this study was to investigate how relevant research
      publications address the validity of diagnostic methods for acute puerperal
      metritis (APM) in dairy cows, a disease commonly treated with antibiotic drugs.
      Therefore, a literature search was conducted in Journal of Dairy Science,
      Theriogenology, Animal Reproduction Science and The Veterinary Journal utilizing
      the ScienceDirect database. The search revealed 259 articles addressing APM.
      After applying exclusion criteria, a total of 48 trials remained. It was
      determined whether the author gave a clear definition of APM, the time of
      diagnosis relative to calving, and the person who performed the diagnosis.
      Studies were checked for the presence of definitions of possible findings,
      thresholds, and test characteristics of the methods used. Overall 9 different
      diagnostic methods were employed. On average 2.5 +/- 1.75 diagnostic methods were
      used in a study. References to support the use of the diagnostic methods were
      provided in 10 of 48 articles (20.8%). Vaginal discharge, transrectal palpation
      and rectal temperature were examined in 39, 22, and 21 of the studies,
      respectively. Thresholds for diagnostic tests and test characteristics were
      mentioned in 6 and 3 of the 48 articles, respectively. Based on this systematic
      review of 48 research papers the evidence supporting the use of the diagnostic
      methods to identify cows with APM has either been not reported or is weak. In
      conclusion, the reporting of the diagnostic methods to identify cows with APM
      needs to be improved and further high-quality research is necessary to improve
      diagnostic performance of the methods employed.

PMID- 22963733
TI  - Indexed hemodynamic measurements may be inappropriate at body surface area
      extremes.

PMID- 22963734
TI  - Comparison between single and three portal laparoscopic splenectomy in dogs.
AB  - BACKGROUND: Single incision laparoscopic surgery (SILS) is a newly growing
      technique to replace a more invasive conventional multiple portal laparoscopic
      surgery. The objective of this study was to compare single (SILS) with three
      portal (Conventional) laparoscopic splenectomy in dogs. Mongrel dogs (n = 18),
      weighting 15 +/- 3 kg, were selected for this study (n = 12 SILS; n = 6
      conventional). The area from xiphoid to pubis was prepared under aseptic
      conditions in dorsal recumbency with the head down and tilted 30 degree in the
      right lateral position. Pneumoperitoneum was established by CO2 using an
      automatic high flow pressure until achieving 12 mm Hg. Instrumentation used
      consisted of curved flexible-tip 5 mm Maryland forceps and ultracision harmonic
      scalpel for sealing and cutting of the vessels and splenic attachments. RESULTS:
      All dogs recovered uneventfully. The splenectomy procedure using SILS and
      conventional methods were significantly different in the respective operative
      time (29.1 +/- 1.65 vs. 42.0 + 2.69 min) and the length of the surgical scar
      (51.6 +/- 1.34 mm vs. 72.0 +/- 1.63 mm; P < 0.001). There were no post-operative
      wound complication including inflammation, infection, hernia formation and
      dehiscence up to one month after surgery. Meanwhile, the conversion to open
      surgery or application of additional portals was not required in both approaches.
      CONCLUSION: This study demonstrated that SILS is a safe and feasible operation
      and could be used as an alternative approach to three portal (Conventional) for
      splenectomy in dog.

PMID- 22963735
TI  - Synthesis, crystal structure and larvicidal activity of novel diamide derivatives
      against Culex pipiens.
AB  - BACKGROUND: Culex is an important mosquito as vectors for the transmission of
      serious diseases, such as filariasis, West Nile virus, dengue, yellow fever,
      chikungunya and other encephalitides. Nearly one billion people in the developing
      countries are at risk. In order to discover new bioactive molecules and
      pesticides acting on mosquito, we designed active amide structure and synthesized
      a series of novel diamide derivatives. RESULTS: A series of novel diamide
      derivatives were designed and synthesized. Their structures were characterized by
      1 H NMR, FTIR and HRMS. The single crystal structure of compound 6n was
      determined to further elucidate the structure. Biological activities of these
      compounds were tested. Most of them exhibited higher mosquito larvicidal
      activity. Especially compound 6r displayed relatively good activity to reach 70%
      at 2 MUg/mL. CONCLUSION: A practical synthetic route to amide derivatives by the
      reaction of amide with another acid is presented. This study suggests that the
      diamide derivatives exhibited good effective against mosquito.

PMID- 22963737
TI  - "Healthy," "diet," or "hedonic". How nutrition claims affect food-related
      perceptions and intake?
AB  - The main purpose of this study was to investigate the impact of nutrition claims
      on food perceptions and intake among adult men and women, during ad libitum
      snacks. In a three (healthy vs. diet vs. hedonic) by two (normal-weight vs.
      overweight/obese) by two (unrestrained vs. restrained eaters) factorial design,
      164 men and 188 women were invited to taste and rate oatmeal-raisin cookies.
      Despite the fact that the cookies were the same in all conditions, they were
      perceived as being healthier in the "healthy" condition than in the "diet" and
      "hedonic" conditions. The caloric content was estimated as higher by participants
      in the "hedonic" than in the "healthy" condition, by women than by men, and by
      restrained than by unrestrained eaters. Although measured ad libitum cookie
      intake did not differ as a function of experimental condition, overweight
      restrained men ate more than did women from each BMI and restraint category.
      Conversely, overweight restrained women ate less than did men from each BMI and
      restraint category. In conclusion, our manipulations of healthiness and
      "fatteningness" of food were effective in changing perceptions, but were not in
      changing behavior.

PMID- 22963736
TI  - Brain structure predicts risk for obesity.
AB  - The neurobiology of obesity is poorly understood. Here we report findings of a
      study designed to examine the differences in brain regional gray matter volume in
      adults recruited as either Obese Prone or Obese Resistant based on self
      identification, body mass index, and personal/family weight history. Magnetic
      resonance imaging was performed in 28 Obese Prone (14 male, 14 female) and 25
      Obese Resistant (13 male, 12 female) healthy adults. Voxel-based morphometry was
      used to identify gray matter volume differences between groups. Gray matter
      volume was found to be lower in the insula, medial orbitofrontal cortex and
      cerebellum in Obese Prone, as compared to Obese Resistant individuals. Adjusting
      for body fat mass did not impact these results. Insula gray matter volume was
      negatively correlated with leptin concentration and measures of hunger. These
      findings suggest that individuals at risk for weight gain have structural
      differences in brain regions known to be important in energy intake regulation,
      and that these differences, particularly in the insula, may be related to leptin.

PMID- 22963738
TI  - The Dutch Eating Behaviour Questionnaire (DEBQ). Assessment of eating behaviour
      in an aging French population.
AB  - The aim of the study was to develop a French version of the Dutch Eating
      Behaviour Questionnaire (DEBQ) in order to provide a self-report measure for
      French people in the field of gerontology. A short version of the DEBQ was
      administered to 262 participants aged 65years and older. Single and multigroup
      confirmatory analyses were carried out. The fit measures for the three-factor
      model and the factorial invariance models with respect to age, sex and BMI status
      were satisfactory. Three subscales of DEBQ had satisfactory internal consistency.
      Regarding age, the results showed significant differences in emotional eating and
      restrained eating. Concerning sex, women had higher mean scores for emotional
      eating and restrained eating than men. Finally, the overweight older people had
      higher scores for emotional eating than the normal-weight participants. The short
      version of DEBQ should provide a useful measure for researchers and clinicians
      who are interested in exploring eating behaviours among the elderly.

PMID- 22963739
TI  - Effect of organic school meals to promote healthy diet in 11-13 year old
      children. A mixed methods study in four Danish public schools.
AB  - The aim of this study was to investigate whether organic school meals can be an
      effective strategy to provide healthy food to children and promote their healthy
      eating habits. Furthermore, the study aimed to examine pupils' attitudes
      predicting intention and behaviours in relation to organic food and health. An
      observational cross-sectional study was designed, and the participants were 6th
      grade Danish pupils from two schools with organic food provision and two schools
      with non-organic food provision. The pupils were asked to complete an online
      adapted food frequency questionnaire, after which selected pupils were invited to
      focus group interviews. More positive school lunch habits were observed in pupils
      in the organic schools than in the non-organic schools. Generally all the pupils
      had positive attitudes towards organic food and health and this had a significant
      impact on their intention to consume organic food but not on their behaviour. In
      addition, all participants were willing to adopt healthier eating habits in the
      future both at school and in the home. These findings suggest that children
      attending schools where meals include organic ingredients might be more aware of
      healthy foods, organic foods and healthy eating habits.

PMID- 22963740
TI  - Influence of divalent magnesium ion on DNA: molecular dynamics simulation
      studies.
AB  - A large amount of experimental evidence is available on the effect of magnesium
      ions on the structure and stability of DNA double helix. Less is known, however,
      on how these ions affect the stability and dynamics of the molecule. The static
      time average pictures from X-ray structures or the quantum chemical energy
      minimized structures lack understanding of the dynamic DNA-ion interaction. The
      present work addresses these questions by molecular dynamics simulation studies
      on two DNA duplexes and their interaction with magnesium ions. Results show
      typical B-DNA character with occasional excursions to deviated states. We
      detected expected stability of the duplexes in terms of backbone conformations
      and base pair parameter by the CHARMM-27 force field. Ion environment analysis
      shows that Mg2+ retains the coordination sphere throughout the simulation with a
      preference for major groove over minor. An extensive analysis of the influence of
      the Mg2+ ion shows no evidence of the popular predictions of groove width
      narrowing by dipositive metal ion. The major groove atoms show higher occupancy
      and residence time compared to minor groove for magnesium, where no such
      distinction is found for the charge neutralizing Na+ ions. The determining factor
      of Mg2+ ion's choice in DNA binding site evolves as the steric hindrance faced by
      the bulky hexahydrated cation where wider major groove gets the preference. We
      have shown that in case of binding of Mg2+ to DNA non electrostatic contributions
      play a major role. An animated Interactive 3D Complement (I3DC) is available in
      Proteopedia at http://proteopedia.org/w/Journal:JBSD:5.

PMID- 22963741
TI  - False recall and recognition of brand names increases over time.
AB  - Using the Deese-Roediger-McDermott (DRM) paradigm, participants are presented
      with lists of associated words (e.g., bed, awake, night). Subsequently, they
      reliably have false memories for related but nonpresented words (e.g., SLEEP).
      Previous research has found that false memories can be created for brand names
      (e.g., Morrisons, Sainsbury's, Waitrose, and TESCO). The present study
      investigates the effect of a week's delay on false memories for brand names.
      Participants were presented with lists of brand names followed by a distractor
      task. In two between-subjects experiments, participants completed a free recall
      task or a recognition task either immediately or a week later. In two within
      subjects experiments, participants completed a free recall task or a recognition
      task both immediately and a week later. Correct recall for presented list items
      decreased over time, whereas false recall for nonpresented lure items increased.
      For recognition, raw scores revealed an increase in false memory across time
      reflected in an increase in Remember responses. Analysis of Pr scores revealed
      that false memory for lures stayed constant over a week, but with an increase in
      Remember responses in the between-subjects experiment and a trend in the same
      direction in the within-subjects experiment. Implications for theories of false
      memory are discussed.

PMID- 22963742
TI  - Application of digital image cross-correlation and smoothing function to the
      diagnosis of breast cancer.
AB  - Digital image correlation (DIC) algorithm was applied to 2D and 3D B-mode
      ultrasound (US) images to create 2D and 3D elastograms based on displacement
      gradient. The roughness of elastograms caused by signal noises and sub-pixel
      errors could be greatly improved by employing the smoothing function based on the
      penalized least square regression method. Using the smoothed elastogram, the size
      and the relative modulus of the inclusion could be estimated with a reasonable
      accuracy. The study suggests that the 2D and 3D displacement-gradient elastograms
      acquired by the combination of DIC and smoothing function have the potential to
      diagnose pathological tissues in-vivo, and to provide new information that is
      related to tissue structure and/or pathology.

PMID- 22963743
TI  - On the role of spectral markers and stability in spine models.
AB  - We considered various stability issues related to biomechanical models of the
      spine, taking as our point of departure the scalar quantities proposed in Howarth
      et al. (2004). We discussed their significance and applicability by considering
      some mechanical toy models. In particular, we analysed the relevance of the
      behaviour of some of these measurements, namely, the determinant of the Hessian
      matrix and other quantities containing information of a similar spectral nature,
      and the role they may play in this type of studies. We showed that although in
      some cases these markers contain information about the load acting on the
      subject, this information may also be masked and not be detectable from these
      indexes. These models also allowed us to see how a system with these
      characteristics may become highly sensitive even to small load changes, and
      prompted us to put forward the hypothesis that trying to preserve stability at
      all costs might, under some circumstances, be an actual cause for system damage.

PMID- 22963744
TI  - Mechanical behaviour of pressed and sintered titanium alloys obtained from
      prealloyed and blended elemental powders.
AB  - The applicability of irregular prealloyed Ti-6Al-4V powder for the fabrication of
      titanium products by pressing and sintering and its employment as a master alloy
      to obtain the Ti-3Al-2.5V alloy was studied. To this end, the starting powders
      were characterised by dilatometry, differential thermal analysis and XRD. Green
      samples were obtained by cold uniaxial pressing, and the evolution of the
      microstructure over the sintering temperature range 900-1400 degrees C was
      studied. The variation of the final density and mechanical properties with the
      sintering temperature was considered. Based on the study carried out, it can be
      stated that more reliable powders are needed to open the titanium market to new
      applications. A relative density of 95% and diverse microstructural features and
      mechanical properties equivalent to those of biomedical devices can be obtained
      by the pressing and sintering route.

PMID- 22963745
TI  - Tribological evaluation of hydrogel articulations for joint arthroplasty
      applications.
AB  - Characterizing the wear behavior of hydrogel articulations is problematic and a
      standardized method has not yet been developed. The aims of this study were to
      evaluate the wear resistance of hydrogel-on-hydrogel articulations and to assess
      the suitability of a submerged measurement technique as a practical and non
      destructive method in quantifying their wear rates. Five hydrogel bearings were
      tested for 5 million cycles using a pin-on-disk tester. As the test progressed,
      the coefficient of friction increased (Spearman's rho=0.76; p<0.001) while the
      surfaces of the pins were burnished (Spearman's rho=-0.31; p<0.001) and those of
      the disks got rougher (Spearman's rho=0.19; p<0.01). Environmental scanning
      electron microscopy analysis showed no evidence of gross wear and revealed
      similar surface morphology between contacting and non-contacting regions of
      specimens. These results support the finding of low wear, which were -1.4+/-8.3
      and 6.6+/-35.3mm(3)/MC based on submerged and wet weights, respectively. Pins
      displayed higher wear than disks based on submerged weights. This was anticipated
      since surfaces of pins were constantly under load and cross-shear while only a
      portion of the disk in contact with the pin was loaded at a given time. Wet
      weights, on the other hand, indicated higher wear for disks than pins. In
      addition, submerged weights yielded a lower standard error of the mean in wear
      rates than wet weights, 3.7 and 14.6mm(3)/MC, respectively. These results
      indicated that submerged weights were more suitable than wet weights in
      quantifying wear of hydrogels in spite of unwanted effects of swelling.

PMID- 22963746
TI  - Biocompatible low Young's modulus achieved by strong crystallographic elastic
      anisotropy in Ti-15Mo-5Zr-3Al alloy single crystal.
AB  - The elastic anisotropy of the Ti-15Mo-5Zr-3Al (mass%) beta-Ti alloy, an ISO
      certified biomedical material, was investigated using its single crystal. It was
      revealed that the Young's modulus exhibited pronounced anisotropy. The Young's
      modulus was reduced to 44.4GPa along the <100> direction in the Ti-15Mo-5Zr-3Al
      single crystal, that is comparable to that of human cortical bones. We determined
      the strategy that beta-Ti alloys with extremely low moduli can be developed by
      reducing the electron-atom (e/a) ratio in alloys, and by suppressing the
      formation of the omega-phase at the same time. This new knowledge must lead to
      the development of "single crystalline beta-Ti implant materials" as hard tissue
      replacements for reducing the stress shielding effect.

PMID- 22963747
TI  - Roughness evolution of metallic implant surfaces under contact loading and
      nanometer-scale chemical etching.
AB  - Surface damage of metallic implant surface at taper lock and clamped interfaces
      may take place through synergistic interactions between repeated contact loading
      and corrosion. In the present research, we investigated the influence of surface
      roughness and contact loading on the mechanical and chemical damage phenomena.
      Cobalt-chromium (CoCrMo) specimens with two different roughness configurations
      created by milling and grinding process were subjected to normal and inclined
      contact loading. During repeated contact loading, amplitude of surface roughness
      reached a steady value after decreasing during the first few cycles. During the
      second phase, the alternating experiment of rough surface contact and micro
      etching was conducted to characterize surface evolution behavior. As a result,
      surface roughness amplitude continuously evolved-decreasing during contact
      loading due to plastic deformation of contacting asperities and increasing on
      exposure to corrosive environment by the preferential corrosion attack on
      stressed area. Two different instabilities could be identified in the surface
      roughness evolution during etching of contact loaded surfaces: increase in the
      amplitude of dominant wavenumber and increase in amplitude of a small group of
      roughness modes. A damage mechanism that incorporates contact-induced residual
      stress development and stress-assisted dissolution is proposed to elucidate the
      measured instabilities in surface roughness evolution.

PMID- 22963748
TI  - Hydrogels for nucleus replacement--facing the biomechanical challenge.
AB  - Hydrogels are considered promising for disc regeneration strategies. However, it
      is currently unknown whether the destruction of the natural interface between
      nucleus and surrounding structures caused by nucleotomy and an inadequate annulus
      closure diminishes the mechanical competence of the disc. This in vitro study
      aimed to clarify these mechanisms and to evaluate whether hydrogels are able to
      restore the biomechanical behaviour of the disc. Nucleus pressure in an ovine
      intervertebral disc was measured in vivo during day and night and adapted to an
      in vitro axial compressive diurnal (15min) and night (30min) load. Effects of
      different defects on disc height and nucleus pressure were subsequently measured
      in vitro using 30 ovine motion segments. Following cases were considered: intact;
      annulus incision repaired by suture and glue; annulus incision with removal and
      re-implantation of nucleus tissue; and two different hydrogels repaired by suture
      and glue. The intradiscal pressure in vivo was 0.75MPa during day and 0.5MPa
      during night corresponding to an in vitro axial compressive force of 130 and 58N,
      respectively. The compression test showed that neither the implantation of
      hydrogels nor the re-implantation of the natural nucleus, assumed as being the
      ideal implant, was able to restore the mechanical functionality of an intact
      disc. Results indicate the importance of the natural anchorage of the nucleus
      with its surrounding structures and the relevance of an appropriate annulus
      closure. Therefore, hydrogels that are able to mimic the mechanical behaviour of
      the native nucleus may fail in restoring the mechanical behaviour of the disc.

PMID- 22963749
TI  - Herd-level determinants of bovine leukaemia virus prevalence in dairy farms.
AB  - The prevalence of bovine leukaemia virus (BLV) was determined in 113 Michigan
      dairy herds by ELISA testing for anti-BLV antibodies in milk. Additionally, an
      interview regarding management practices with cooperating herd managers
      identified farm-level variables thought to be associated with prevalence of BLV.
      Twenty-three risk factors (P <= 0.1) were identified on one-way ANOVA or simple
      linear regression. Multivariate analysis identified several management practices
      whose predictive value for increased prevalence of BLV may relate to transmission
      among herd mates, e.g. reuse of hypodermic needles, lack of fly control, gouge
      dehorning and increased use of injections in dry cows. Additionally, exclusive
      breeding of heifers with artificial insemination was associated with decreased
      BLV prevalence, as compared with at least some use of natural service by a bull.
      Although intervention studies are needed before causal relationships can be
      concluded, and unaccounted variables related to transmission exist among dairy
      herds, these findings suggest management practices that may help dairy producers
      reduce the transmission of BLV within their herds.

PMID- 22963750
TI  - G-CSF stimulation and coronary reinfusion of mobilized circulating mononuclear
      proangiogenic cells in patients with chronic ischemic heart disease:five-year
      results of the TOPCARE-G-CSF trial.
AB  - Prognosis of patients with heart failure remains poor despite improved
      conventional and interventional treatment regimens. The improvement of
      neovascularization and repair processes by administration of bone marrow-derived
      cells modestly improved the recovery after acute myocardial infarction. However,
      circulating patient-derived cells are reduced in number and function particularly
      in chronic heart failure. Therefore, we tested the hypothesis whether the
      mobilization of circulating mononuclear proangiogenic cells (CPCs) by G-CSF may
      overcome some of these limitations. In the present pilot study, 32 patients with
      at least 3-month-old myocardial infarction were randomized to G-CSF alone (G-CSF
      group) or intracoronary infusion of G-CSF-mobilized and cultured CPCs into the
      infarct-related artery (G-CSF/CPC group). Primary endpoint of the study was
      safety. Efficacy parameters included serial assessment of LV function, NT-proBNP
      levels, and cardiopulmonary exercise testing. G-CSF effectively mobilized
      circulating CD34(+)CD45(+) cells after 5 days in all patients (408 +/- 64%)
      without serious adverse events. At 3 months, NYHA class and global LV function
      did not show significant improvements in both treatment groups (G-CSF: DeltaLVEF
      1.6 +/- 2.4%; p = 0.10; G-CSF/CPC: DeltaLVEF 1.4 +/- 4.1%; p = 0.16). In
      contrast, target area contractility improved significantly in the G-CSF/CPC
      group. During 5-year follow-up, one patient died after rehospitalization for
      worsening heart failure. Eleven patients underwent further revascularization
      procedures. NT-proBNP levels, cardiopulmonary exercise capacity, and NYHA class
      remained stable in both treatment groups. The results from our pilot trial
      indicate that administration of G-CSF alone or G-CSF-mobilized and cultured CPCs
      can be performed safely in patients with chronic ischemic heart disease. However,
      only minor effects on LV function, NT-proBNP levels, and NYHA classification were
      observed during follow-up, suggesting that the enhancement of CPCs by G-CSF alone
      does not substantially improve intracoronary cell therapy effects in patients
      with chronic ischemic heart failure.

PMID- 22963752
TI  - Positive outcome of average volume-assured pressure support mode of a Respironics
      V60 Ventilator in acute exacerbation of chronic obstructive pulmonary disease: a
      case report.
AB  - INTRODUCTION: We were able to treat a patient with acute exacerbation of chronic
      obstructive pulmonary disease who also suffered from sleep-disordered breathing
      by using the average volume-assured pressure support mode of a Respironics V60
      Ventilator (Philips Respironics: United States). This allows a target tidal
      volume to be set based on automatic changes in inspiratory positive airway
      pressure. This removed the need to change the noninvasive positive pressure
      ventilation settings during the day and during sleep. The Respironics V60
      Ventilator, in the average volume-assured pressure support mode, was attached to
      our patient and improved and stabilized his sleep-related hypoventilation by
      automatically adjusting force to within an acceptable range. CASE PRESENTATION:
      Our patient was a 74-year-old Japanese man who was hospitalized for treatment due
      to worsening of dyspnea and hypoxemia. He was diagnosed with acute exacerbation
      of chronic obstructive pulmonary disease and full-time biphasic positive airway
      pressure support ventilation was initiated. Our patient was temporarily provided
      with portable noninvasive positive pressure ventilation at night-time following
      an improvement in his condition, but his chronic obstructive pulmonary disease
      again worsened due to the recurrence of a respiratory infection. During the
      initial exacerbation, his tidal volume was significantly lower during sleep
      (378.9 +/- 72.9mL) than while awake (446.5 +/- 63.3mL). A ventilator that allows
      ventilation to be maintained by automatically adjusting the inspiratory force to
      within an acceptable range was attached in average volume-assured pressure
      support mode, improving his sleep-related hypoventilation, which is often
      associated with the use of the Respironics V60 Ventilator. Polysomnography
      performed while our patient was on noninvasive positive pressure ventilation
      revealed obstructive sleep apnea syndrome (apnea-hypopnea index = 14), suggesting
      that his chronic obstructive pulmonary disease was complicated by obstructive
      sleep apnea syndrome. CONCLUSION: In cases such as this, in which patients with
      severe acute respiratory failure requiring full-time noninvasive positive
      pressure ventilation therapy also show sleep-disordered breathing, different
      ventilator settings must be used for waking and sleeping. On such occasions, the
      Respironics V60 Ventilator, which is equipped with an average volume-assured
      pressure support mode, may be useful in improving gas exchange and may achieve
      good patient compliance, because that mode allows ventilation to be maintained by
      automatically adjusting the inspiratory force to within an acceptable range
      whenever ventilation falls below target levels.

PMID- 22963751
TI  - Clinical validity of outcome pain measures in naturally occurring canine
      osteoarthritis.
AB  - BACKGROUND: The conceptual validity of kinetic gait analysis and disability
      outcome assessment methods has guided their use in the assessment of pain caused
      by osteoarthritis (OA). No consensus on the best clinical methods for pain
      evaluation in canine OA exists, particularly, when evaluating treatments where a
      smaller treatment effect is anticipated than with pharmacological pain killers.
      This study thus aimed at determining the technical validity of some clinical
      endpoints on OA pain in dogs using the green-lipped mussel (GLM)-enriched
      diet.Twenty-three adult dogs with clinical OA completed the prospective
      controlled study. All the dogs were fed a balanced diet over a 30-day control
      period followed by a GLM-enriched diet over a 60-day period. The kinetic gait
      analysis parameter (PVF(BW), peak vertical force adjusted for body weight
      change), electrodermal activity (EDA), and a standardized multifactorial pain
      questionnaire (MFQ) were performed on day (D) 0 (inclusion), D30 (start) and D90
      (end). The owners completed a client-specific outcome measures (CSOM) instrument
      twice a week. Motor activity (MA) was continuously recorded in seven dogs using
      telemetered accelerometric counts. We hypothesized that these methods would
      produce convergent results related to diet changes. A Type I error of 0.05 was
      adjusted to correct for the multiplicity of the primary clinical endpoints.
      RESULTS: Neither the EDA nor the MFQ were found reliable or could be validated.
      Changes in the PVFBW (P(adj) = 0.0004), the CSOM (P(adj) = 0.006) and the MA
      intensity (P(adj) = 0.02) from D0 to D90 suggested an effect of diet(s). Only the
      PVFBW clearly increased after the GLM-diet (P(adj) = 0.003). The CSOM exhibited a
      negative relationship with the PVF(BW) (P = 0.02) and MA duration (P = 0.02).
      CONCLUSIONS: The PVF(BW) exhibited the best technical validity for the
      characterization of the beneficial effect of a GLM-enriched diet. The CSOM and MA
      appeared less responsive following a GLM-diet, but these measures appeared
      complementary to gait analysis. Apparently, the CSOM provides the capacity to
      rely on pain OA assessment influenced by both lameness quantification (PVF(BW))
      and physical functioning (MA).

PMID- 22963753
TI  - Protein flexibility and conformational states of Leishmania antigen eIF-4A:
      identification of a novel plausible protein adjuvant using comparative genomics
      and molecular modeling.
AB  - Recent homology modeling studies have identified specific residues (epitope) of
      the Leishmania RNA helicase protein (LmeIF) that stimulates production of IL-12
      cytokine. However, question remains concerning how LmeIF's N-terminal moiety
      initiates adjuvant effects. Extensive molecular modeling combining the normal
      mode analysis (NMA) and molecular dynamics simulations, in the present study, has
      demonstrated that the LmeIF structure may exist in two different forms
      corresponding to the extended and collapsed (closed) states of the entire
      structure. The computational results showed that the two domains of the LmeIF
      structure tend to undergo large fluctuations in a concerted fashion and have
      strong effect on the solvent accessible surface of the epitope situated on the N
      terminal structure. The conformational freedom of the C-terminal domains may
      explain why the entire LmeIF protein is not as active as the N-terminal moiety.
      Thereafter, a comparative genome analysis with subsequent homology modeling and
      molecular electrostatic potential (MEP) techniques allowed us to predict a novel
      and plausible RNA helicase (LI-helicase) from the Listeria source with adjuvant
      property as observed for the Leishmania eIF-4A protein. The structural folding
      and MEP maps revealed similar topologies of the epitope of both LmeIF and LI
      helicase proteins and striking identity in the local disposition of the charged
      groups. An animated Interactive 3D Complement (I3DC) is available in Proteopedia
      at http://proteopedia.org/w/Journal:JBSD:7. 

PMID- 22963754
TI  - Cross-over study of topical anaesthesia with tetracaine solution for transoral
      rigid laryngoscopy.
AB  - BACKGROUND: Transoral rigid laryngoscopy with videostroboscopy is the most
      practical method to visualise the vocal folds. The optimal topical anaesthesia
      regimen for transoral rigid laryngoscopy has not yet been established. OBJECTIVE:
      To compare patient comfort and compliance with various topical anaesthetics for
      transoral rigid laryngoscopy. METHODS: Each of 10 patients received a random
      topical administration of either 2 per cent lidocaine gel, 1 per cent tetracaine
      gel or 1 per cent tetracaine solution, 10 minutes before undergoing rigid
      laryngoscopy with videostroboscopy. During follow-up laryngoscopies, the agent
      with the lowest mean visual analogue scale score for discomfort was then used to
      study the timing of topical anaesthetic application: the agent was given to the
      patient 5, 10 or 15 minutes before laryngoscopy (with the timing randomly
      selected). RESULTS: Compared with lidocaine gel or tetracaine gel, laryngoscopy
      with topical tetracaine solution was more comfortable. There was a statistically
      significant difference in discomfort score between the 5 and 10 minute
      application groups, but not between the 10 and 15 minute groups. CONCLUSION:
      Tetracaine solution, applied topically 10 minutes before transoral rigid
      laryngoscopy, significantly decreases patient discomfort.

PMID- 22963755
TI  - Smoking among adolescents in Northern Greece: a large cross-sectional study about
      risk and preventive factors.
AB  - BACKGROUND: The aim of the present study was to investigate epidemiological data
      about cigarette smoking in relation with risk and preventive factors among Greek
      adolescents. METHODS: We randomly selected 10% of the whole number of schools in
      Northern Greece (133 schools, 18,904 participants were included). Two anonymous
      questionnaires (smoker's and non-smoker's) were both distributed to all students
      so they selected and filled in only one. A parental signed informed consent was
      obtained using an informative leaflet about adolescent smoking. RESULTS: The main
      findings of the study were: a) 14.2% of the adolescents (mean age+/-SD: 15.3+/
      1.7 years) reported regular smoking (24.1% in the age group 16-18 years), b)
      84.2% of the current smokers reported daily use, c) students who live in urban
      and semirural areas smoke more frequently than those in rural areas, d) students
      in technically oriented schools smoke twice as frequent compared to those in
      general education, e) risk factors for smoking: male gender, low educational
      level of parents, friends who smoke (OR: 10.01, 95%CI: 8.53-11.74, p<0.001),
      frequent visits to internet cafes (OR:1.53, 95%CI: 1.35-1.74, p<0.001), parents,
      siblings (OR:2.24, 95%CI: 1.99-2.51, p<0.001) and favorite artist (OR:1.18,
      95%CI: 1.04-1.33, p=0.009) who smoke, f) protective factors against smoking:
      participation in sports (OR:0.59, 95%CI: 0.53-0.67, p<0.001), watching television
      (OR:0.74, 95%CI 0.66-0.84, p<0.001) and influence by health warning messages on
      cigarette packets (OR:0.42, 95%CI: 0.37, 0.48, p<0.001). CONCLUSIONS: Even though
      prevalence of cigarette smoking is not too high among Greek adolescents,
      frequency of everyday cigarette use is alarming. We identified many social and
      lifestyle risk and preventive factors that should be incorporated in a national
      smoking prevention program among Greek adolescents.

PMID- 22963756
TI  - Giant presacral schwannoma presenting with constipation: a case report.
AB  - INTRODUCTION: Schwannoma, otherwise known as a neurilemmoma, is a tumor arising
      from peripheral nerve sheaths. Although commonly noted in association with the
      eighth cranial nerve as intracranial acoustic neuroma, cases of schwannoma
      arising in other locations have been reported in the literature. These tumors
      usually cause symptoms as a result of their mass effect and, since they are
      benign, encapsulated and non-invasive tumors, complete surgical excision is
      considered curative. CASE PRESENTATION: We report the case of a 46-year-old Sri
      Lankan man who presented to our facility with recent onset of difficulty
      evacuating his bowels. He was noted to have a giant presacral schwannoma on
      magnetic resonance imaging scan. The mass was surgically excised with improvement
      of our patient's symptoms. A subsequent histopathological examination confirmed
      the presence of a benign schwannoma. CONCLUSIONS: Although schwannomas commonly
      occur in the extremities, a rare case of occurrence in the pelvis is reported
      here. Due to the limited space in the pelvis, the local mass effect may be the
      presenting feature of such a lesion and surgical excision is curative.

PMID- 22963757
TI  - Allogeneic adipose-derived stem cells with low immunogenicity constructing tissue
      engineered bone for repairing bone defects in pigs.
AB  - The ideal cells for tissue engineering should have the following characteristics:
      easy obtainment, safety, immune privilege, the capability of self-renewal, and
      multipotency. Adipose-derived stem cells (ADSCs) are a promising candidate.
      However, the immunogenicity of allogeneic mesenchymal  stem cells limits their
      long-term benefits. In this study, we introduced human cytomegalovirus US2/US3
      gene into the ADSCs to decrease the expression of MHC I protein of ADSCs and
      reduce the activation of T-cells of the recipient animals. Moreover, the
      biosafety and biological characteristics  of ADSCs transfected with the US2/US3
      genes (ADSCs-US2/US3) were similar to normal ADSCs. Then we took ADSCs-US2/US3 to
      construct a tissue-engineered bone for repairing bone defects in pigs and found
      that there were no great differences in repair effects or healing time between
      the allogeneic  ADSCs-US2/US3 group and the autologous ADSC group. These results
      suggest that allogeneic ADSCs-US2/US3 have the advantages of biological safety,
      low immunogenicity, and effective osteogenesis. Such barely immunogenic ADSCs
      will be crucial for the success of future tissue-regenerative approaches.

PMID- 22963758
TI  - Delayed carotid blow-out syndrome: a new complication of chemoradiotherapy
      treatment in pharyngolaryngeal carcinoma.
AB  - BACKGROUND: Carotid blow-out syndrome is one of the most devastating
      complications of head and neck carcinoma. It usually occurs as a post-operative
      complication or when the tumour compromises the vascular axis. METHODS AND
      RESULTS: We report two patients who suffered carotid blow-out syndrome but who
      did not have the usual predisposing factors. Both patients had a
      pharyngolaryngeal carcinoma that was treated with chemoradiotherapy. Residual non
      tumoural ulceration was seen along the lateral wall of the hypopharynx in both
      cases. This ulceration eventually reached the vascular axis, precipitating
      carotid rupture and death. CONCLUSION: Residual non-tumoural ulceration of the
      lateral wall of the hypopharynx after chemoradiotherapy should be considered with
      the utmost caution. Once persistence of the tumour is excluded, surgery is
      indicated to protect the vascular axis, in order to prevent carotid blow-out
      syndrome.

PMID- 22963759
TI  - Guillotine versus dissection tonsillectomy: randomised, controlled trial.
AB  - OBJECTIVE: This trial aimed to compare the guillotine technique of tonsillectomy
      with 'cold steel' dissection, the current 'gold standard'. DESIGN: A single
      centre, randomised, controlled trial. METHODS: One hundred children aged 3 to 11
      years who were listed for bilateral tonsillectomy were recruited. Patients had
      one tonsil removed by each technique, and were blinded to the side. The operative
      time, intra-operative blood loss, haemostasis requirement and post-operative pain
      scores were recorded and compared. RESULTS: Operative time and intra-operative
      blood loss were both significantly less for the guillotine technique (p < 0.001)
      and there was a significantly reduced haemostasis requirement (p < 0.001). Pain
      was also less on the guillotine side (p < 0.001). There were no tonsillar
      remnants or palatal trauma for either technique. There was no significant
      difference between techniques in the frequency of secondary haemorrhage.
      CONCLUSION: This study provides level Ib evidence that guillotine tonsillectomy
      in children with mobile tonsils is an effective and time-efficient procedure
      which produces less intra-operative blood loss and post-operative pain than cold
      steel dissection.

PMID- 22963760
TI  - Survival and functional restoration of human fetal ventral mesencephalon
      following transplantation in a rat model of Parkinson's disease.
AB  - Cell replacement therapy by intracerebral transplantation of fetal dopaminergic
      neurons has become a promising therapeutic option for patients suffering from
      Parkinson's disease during the last decades. However, limited availability of
      human fetal tissue as well as ethical issues, lack of alternative nonfetal donor
      cells, and the absence of standardized transplantation protocols have prevented
      neurorestorative therapies from becoming a routine procedure in patients
      suffering from neurodegenerative diseases. Improvement of graft survival, surgery
      techniques, and identification of the optimal target area are imperative for
      further optimization of this novel treatment. In the present study, human primary
      fetal ventral mesencephalon-derived tissue from 7- to 9-week-old human fetuses
      was transplanted into 6-hydroxydopamine-lesioned adult Sprague-Dawley rats. Graft
      survival, fiber outgrowth, and drug-induced rotational behavior up to 14 weeks
      posttransplantation were compared between different intrastriatal transplantation
      techniques (full single cell suspension vs. partial tissue pieces suspension
      injected by glass capillary or metal cannula) and the intranigral glass capillary
      injection of a full (single cell) suspension. The results demonstrate a higher
      survival rate of dopamine neurons, a greater reduction in amphetamine-induced
      rotations (overcompensation), and more extensive fiber outgrowth for the
      intrastriatally transplanted partial (tissue pieces) suspension compared to all
      other groups. Apomorphine-induced rotational bias was significantly reduced in
      all groups including the intranigral group. The data confirm that human ventral
      mesencephalon-derived cells serve as a viable cell source, survive in a
      xenografting paradigm, and functionally integrate into the host tissue. In
      contrast to rat donor cells, keeping the original (fetal) neuronal network by
      preparing only a partial suspension containing tissue pieces seems to be
      beneficial for human cells, although a metal cannula that causes greater tissue
      trauma to the host is required for injection. In addition, homotopic intranigral
      grafts may represent a complimentary grafting approach to the "classical" ectopic
      intrastriatal target site in PD. 

PMID- 22963761
TI  - Involvement of focal adhesion kinase in cellular proliferation, apoptosis and
      prognosis of laryngeal squamous cell carcinoma.
AB  - OBJECTIVE: This study aimed to investigate the relationship between focal
      adhesion kinase expression and clinicopathological factors, cell apoptosis and
      proliferation, and overall survival, in laryngeal squamous cell carcinoma.
      METHODS: Immunohistochemical staining was used to detect the expression of focal
      adhesion kinase and proliferating cell nuclear antigen in tissue samples.
      Apoptotic cells were assessed using the terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labelling ('TUNEL') method. RESULTS:
      The proportion of focal adhesion kinase expression was 73.26 per cent in tumour
      tissues, significantly greater than in normal tissues (p < 0.05), and was
      significantly related to laryngeal cancer clinical stage, lymph node metastasis
      and overall survival (p < 0.05). In the tumour cases assessed, up-regulation of
      focal adhesion kinase expression was significantly associated with decreased cell
      apoptosis and increased proliferation (p < 0.05). CONCLUSION: These findings
      suggest that focal adhesion kinase may affect laryngeal squamous cell carcinoma
      progression through regulation of cell apoptosis and proliferation. Focal
      adhesion kinase expression is a major prognostic factor in laryngeal cancer
      patients.

PMID- 22963762
TI  - [Transient delayed paraplegia after repair of thoracic and thoracoabdominal
      aneurysms].
AB  - Thoracoabdominal aneurysm requires multidisciplinary management due to its
      complexity both in surgical technique and anesthetic considerations. One of the
      most feared postoperative complication is spinal cord ischemia. It can be
      presented as different clinical patterns, and its recovery may be partial or
      complete. The postoperative management of spinal cord ischemia is mainly based on
      techniques to increase spinal cord perfusion, above all, hemodynamic stability
      and cerebrospinal fluid drainage. We present two cases of delayed paraplegia
      after an open repair of a thoracoabdominal aneurysm and a descending thoracic
      aortic aneurysm repair using an endovascular stent graft. They both had a
      complete neurological recovery after cerebrospinal fluid drainage. 

PMID- 22963763
TI  - Novel AI-2 quorum sensing inhibitors in Vibrio harveyi identified through
      structure-based virtual screening.
AB  - In this letter, a high-throughput virtual screening was accomplished to identify
      potent inhibitors against AI-2 quorum sensing on the basis of Vibrio harveyi
      LuxPQ crystal structure. Seven compounds were found to inhibit AI-2 quorum
      sensing with IC(50) values in the micromolar range, and presented low
      cytotoxicity or no cytotoxicity in V. harveyi.

PMID- 22963764
TI  - Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5
      antagonists.
AB  - 1H-pyrrolo[2,3-c]pyridine-7-carboxamides constitute a new series of allosteric
      mGluR5 antagonists. Variation of the substituents attached to the heterocyclic
      scaffold allowed to improve the physico-chemical parameters for optimization of
      the aqueous solubility while retaining high in vitro potency.

PMID- 22963765
TI  - Chiral separation, configurational identification and antihypertensive evaluation
      of (+/-)-7,8-dihydroxy-3-methyl-isochromanone-4.
AB  - (+/-)-7,8-Dihydroxy-3-methyl-isochromanone-4 [(+/-)-XJP] is a natural
      antihypertensive product contained in banana (Musa sapientum L.) peel. (-)-XJP
      and (+)-XJP were first obtained by chiral resolution, meanwhile circular
      dichroism (CD) calculations and chiral synthesis were employed to investigate the
      absolute configuration. The results indicated that the absolute configuration of
      (+)-XJP is S-configured and the absolute configuration of (-)-XJP is R
      configured. Furthermore, the evaluation of antihypertensive effects in vivo
      proved that R-(-)-XJP was more potent than S-(+)-XJP and [(+/-)-XJP].

PMID- 22963766
TI  - 1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2
      isoform of pyruvate kinase.
AB  - Cancer cells preferentially use glycolysis rather than oxidative phosphorylation
      for their rapid growth. They consume large amount of glucose to produce lactate
      even when oxygen is abundant, a phenomenon known as the Warburg effect. This
      metabolic change originates from a shift in the expression of alternative spliced
      isoforms of the glycolytic enzyme pyruvate kinase (PK), from PKM1 to PKM2. While
      PKM1 is constitutively active, PKM2 is switched from an inactive dimer form to an
      active tetramer form by small molecule activators. The prevalence of PKM2 in
      cancer cells relative to the prevalence of PKM1 in many normal cells, suggests a
      therapeutic strategy whereby activation of PKM2 may counter the abnormal cellular
      metabolism in cancer cells, and consequently decreased cellular proliferation.
      Herein we describe the discovery and optimization of a series of PKM2 activators
      derived from the 2-((2,3-dihydrobenzo[b][1,4] dioxin-6-yl)thio)-1-(2-methyl-1
      (methylsulfonyl)indolin-5-yl) ethanone scaffold. The synthesis, SAR analysis,
      enzyme active site docking, enzymatic reaction kinetics, selectivity and
      pharmaceutical properties are discussed.

PMID- 22963767
TI  - [Situations where natriuretic peptides may be useful].

PMID- 22963768
TI  - Comparative testing of various pancreatic cancer stem cells results in a novel
      class of pancreatic-cancer-initiating cells.
AB  - No systemic therapy is effective against pancreatic cancer (PC). Pancreatic
      cancer stem cells (PCSC) are hypothesized to account for therapeutic resistance.
      Several PCSC subpopulations were reported, each characterized by different
      markers. To be able to target PCSC, we sought to better define this putative
      heterogeneity. Therefore, we tested most of the known putative PCSC markers in
      established and fresh tumor cell lines. CD20, CD24, CD44, CD133, CD184 (CXCR4),
      CD326 (EpCam, ESA), Sox-2, OCT 3/4, and the side-population (SP) were tested in
      five PC cell lines, and the effects of confluency, hypoxia, radiation, and
      gemcitabine on the SP. The testing phase suggested several putative PCSC
      populations that were further tested and validated for their tumor-initiating
      capacity against known PCSC in 3 established and 1 fresh PC cell lines. Cell
      surface and intracellular markers showed significant variability among cell
      lines. SP was the only common marker in all cell lines and consistently less than
      1%. SP response to confluence, hypoxia, radiation, and gemcitabine was
      inconsistent between cell lines. The initial testing phase suggested that SP/CD44
      CD24-CD326+ cells might be a novel PCSC subpopulation. Tumor initiation capacity
      tests in nude mice confirmed their increased tumorigenicity over previously
      reported PCSC. Our data better define the heterogeneity of reported PCSC in cell
      lines tested in this study. We propose that prior to targeting PC via PCSC, one
      will need to gain more insight into this heterogeneity. Finally, we show that
      SP/CD44-CD24-CD326+ cells are a novel subpopulation of pancreatic cancer tumor
      initiating cells. Further mechanistic studies may lead to better targeting of PC
      via targeting this novel PCSC.

PMID- 22963769
TI  - Do women make an informed choice about participating in breast cancer screening?
      A survey among women invited for a first mammography screening examination.
AB  - OBJECTIVE: To determine the level of informed choice in women invited for breast
      cancer screening for the first time. METHODS: To determine the content of
      decision-relevant knowledge, 16 experts were asked to judge whether each of 51
      topics represented essential information to enable informed choices. To assess
      the level of informed choices, a questionnaire was then sent to all 460 invited
      women in the south-western part of the Netherlands who turned 50 in August 2008.
      RESULTS: Of all 229 respondents, 95% were deemed to have sufficient knowledge as
      they answered at least 8 out of 13 items correctly. In 90% there was consistency
      between intention (not) to participate and attitude. As a result, 88% made an
      informed choice. Sixty-eight percent of women responded correctly on the item of
      over-diagnosis. Even if all non-respondents were assumed to have no knowledge,
      50% of the total group invited to participate still had sufficient knowledge.
      CONCLUSIONS: Women were deemed to have sufficient relevant knowledge of the
      benefits and harms if they answered at least half of the items correctly.
      PRACTICE IMPLICATIONS: To further increase informed choices in breast cancer
      screening, information on some of the possible harms merits further attention.

PMID- 22963771
TI  - Travel clinic consultation and risk assessment.
AB  - A significant number of travellers sustain travel-related injury or illness,
      despite receiving pretravel advice. This appears to be due to a combination of
      inconsistent guidance about risks and recommendations, and partial adherence.
      This article considers perceptions and attitudes to risk, factors affecting
      uptake of advice, and features of an effective consultation. A framework is
      proposed for a pretravel consultation, using a shared decision-making approach.
      Engaging the traveller as an active participant in maintaining their own health
      and providing balanced, evidence-based information about risks and benefits is
      predicted to enhance the effectiveness of the pretravel consultation.

PMID- 22963772
TI  - Vaccine-preventable diseases and their prophylaxis.
AB  - Global uptake of new vaccines shapes the epidemiology of infections, and in turn
      this changing epidemiology guides vaccine development. Once introduced,
      surveillance and monitoring of the impact of vaccines on disease and adverse
      events is vital for further development. This article reviews the use of vaccines
      as part of routine health care, vaccines that may be required for entry into a
      destination country, and vaccines that are recommended because of risk during
      travel. Considerations and advances in the vaccination of travelers are
      addressed.

PMID- 22963770
TI  - Regulation of human growth and differentiation factor 3 gene expression by NANOG
      in human embryonic carcinoma NCCIT cells.
AB  - We investigated transactivation by NANOG in regulating growth and differentiation
      factor 3 (GDF3) expression in NCCIT cells. GDF3 expression was affected by shRNA
      mediated downregulation and by exogenous overexpression of NANOG specifically, as
      well as by retinoic acid-mediated differentiation. GDF3 transcription was
      activated by NANOG, and the upstream region (-183 to -1) was sufficient to induce
      minimal transcriptional activity. Moreover, NANOG binds to the GDF3 minimal
      promoter in vivo and the transcriptional activity is mediated by NANOG
      transactivation domain. This study provides the first evidence that NANOG is a
      transcriptional activator of the expression of the oncogenic growth factor GDF3
      in embryonic carcinoma cells.

PMID- 22963773
TI  - The immunosuppressed traveler.
AB  - This article reviews the normal immune response to vaccines. It describes the
      effect of different immunosuppressive therapies (glucocorticoids, inhibitors of
      calcineurin and mTOR, azathioprine, mycophenolate acid, methotrexate, depleting
      and nondepleting monoclonal antibodies, and tumor necrosis factor antagonists) on
      critical steps in the cellular and humoral immune responses to vaccines. The
      impact of age-related involution of thymus and bone marrow on the immune
      reconstitution in allogeneic hematopoietic cell transplant recipients and human
      immunodeficiency virus is covered. A practical approach to vaccinating and
      preparing travelers with severe immunosuppression is proposed.

PMID- 22963774
TI  - Visiting relatives and friends (VFR), pregnant, and other vulnerable travelers.
AB  - With industrial development and expanding tourism, many people now have an
      opportunity to travel to many previously unreachable foreign destinations.
      Travelers with medical or physical conditions or who are vulnerable because of
      pregnancy or age (pediatric or elderly traveler), require specialist support and
      advice before traveling. Immigrants who return to their country of birth to visit
      relatives and friends should be classified as vulnerable travelers, as they have
      been shown to carry a disproportionate burden of travel-related morbidity. In
      this article, we explore the major risks to health and the main preventive
      strategies appropriate to the most vulnerable travelers.

PMID- 22963775
TI  - Malaria prevention in travelers.
AB  - A common approach to malaria prevention is to follow the "A, B, C, D" rule:
      Awareness of risk, Bite avoidance, Compliance with chemoprophylaxis, and prompt
      Diagnosis in case of fever. The risk of acquiring malaria depends on the length
      and intensity of exposure; the risk of developing severe disease is primarily
      determined by the health status of the traveler. These parameters need to be
      assessed before recommending chemoprophylaxis and/or stand-by emergency
      treatment. This review discusses the different strategies and drug options
      available for the prevention of malaria during and post travel.

PMID- 22963776
TI  - Insect bite prevention.
AB  - Protection from the bites of arthropod (insect and acarine) vectors of disease is
      the first line of defense against disease transmission and should be advised in
      all cases when traveling abroad. Details are described of the main approaches for
      the prevention of bites, including topical or skin repellents, impregnated
      clothing, bed nets, and spatial or aerial repellents and aerosols. The bionomics
      of the main arthropod vectors of disease are described along with photographic
      plates and tabulated advice to give the traveler. An in-depth treatment of the
      different protection methodologies provides an up-to-date overview of the
      technologies involved.

PMID- 22963777
TI  - Travel-associated skin disease.
AB  - Travel associated skin disease is extremely common and a frequent cause of the
      returning traveller seeking medical attention. Widespread cutaneous eruptions
      usually represent reactive rashes, indicating an underlying systemic infection or
      allergic reaction. Patients with disseminated or spreading rashes following
      travel often present with fever and malaise. In contrast, those presenting with
      localised skin disease such as a blister, nodule, plaque, ulcer etc are usually
      well in themselves but have sustained a bite/sting/penetrating injury or
      introduction of infection directly into the skin at the affected site. As a
      general rule widespread rashes are investigated with blood tests/serology and
      localised lesions with a skin biopsy for culture and histology.

PMID- 22963778
TI  - Traveler's Diarrhea.
AB  - Travelers' diarrhea (TD) is the most important health issue among international
      travelers. In high risk areas, 50-90% of travelers may experience an episode of
      TD. The risk of acquiring TD is influenced by factors such as the destination,
      duration of stay, standard of accommodation, type of travel, age of the traveler,
      and also by individual risk factors. Most cases of TD are caused by bacteria;
      treatment for TD are loperamide and antibiotics. Preventive strategies such as
      hygiene measures have limited impact. Prophylactic intake of antibiotics or
      vaccines to prevent from TD can be considered in special situations.

PMID- 22963779
TI  - Environmental hazards, hot, cold, altitude, and sun.
AB  - There has been an increase in both recreational and adventure travel to extreme
      environments. Humans can successfully acclimatize to and perform reasonably well
      in extreme environments, provided that sufficient time is given for
      acclimatization (where possible) and that they use appropriate behavior. This is
      aided by a knowledge of the problems likely to be encountered and their
      prevention, recognition, and treatment.

PMID- 22963780
TI  - Mass gatherings and infectious diseases: prevention, detection, and control.
AB  - Mass gatherings have attracted the attention of the medical community because of
      the increased demand made on existing services and the potential for public
      health problems resulting from changes in population dynamics and behaviors.
      Crowding, lack of hygiene, and rapid population movement at mass gatherings can
      lead to the emergence of infectious diseases, with the potential for spread
      across the globe. Numerous infections pose considerable challenges to organizers
      of mass gatherings and the hosts of these events. This review highlights the
      risks of infectious diseases, and key interventions for their prevention, at mass
      gatherings.

PMID- 22963781
TI  - Rabies: relevance, prevention, and management in travel medicine.
AB  - Rabies is a zoonotic viral disease, transmitted only in mammals. Terrestrial
      rabies, predominantly transmitted by dogs, is the most important rabies cycle
      threatening humans. The causative neurotropic virus is a negative-stranded RNA
      virus of the family Rhabdoviridae, genus Lyssavirus. This genus contains several
      rabies-related viruses. All variants are known or suspected to cause rabieslike
      diseases. Transmission occurs by the virus entering through the skin or the
      mucosa after bites, scratches, or preexisting injuries contaminated by the saliva
      of an infected mammal. Only 51 human rabies cases that have not been transmitted
      by animal bites are described.

PMID- 22963782
TI  - Parasitic liver disease in travelers.
AB  - Liver disease is an important source of morbidity among ill returning travelers.
      Jaundice is one of the most common and obvious symptoms of liver disease, the
      differential diagnosis of which is extensive, especially in travelers. Jaundice
      in travelers can arise from both infectious and noninfectious causes. We herein
      summarize the most common parasitic etiologies that may lead to jaundice in the
      returned traveler, visitors of friends and relatives, or new immigrants, and
      describe the etiology, epidemiology, and pathogenesis of clinical features of
      each.

PMID- 22963783
TI  - Eosinophilia in the returning traveler.
AB  - An elevated eosinophil count is a common, frequently underrecognized finding in
      travelers returning from the tropics and elsewhere. Although there are multiple
      causes of eosinophilia in a traveler, it is often related to an acquired helminth
      infection. In some cases these infections can be benign and self-limiting, but in
      others it may lead to severe sequelae for the individual or others. This article
      outlines the etiology and diagnosis of eosinophilia concentrating on helminth
      infections.

PMID- 22963784
TI  - Travel trends and patterns of travel-associated morbidity.
AB  - Improved data collection methods have produced a clearer picture of travel
      associated health risks and at-risk travelers. Examination of the causes of
      mortality and morbidity has led to a change in emphasis on ways of reducing
      morbidity. There are unanswered questions that relate to the contribution of
      medical comorbidities on travel-associated illness, how communication can enhance
      or influence behavior change, and the best strategies to influence the travelers
      at greatest risk. Enhanced data collection methods and better denominator data
      are necessary to provide more precise risk information and help inform policy and
      thereby reduce morbidity in tourists and travelers.

PMID- 22963785
TI  - Laboratory investigations and diagnosis of tropical diseases in travelers.
AB  - Evaluation of an individual traveler returned from the tropics requires
      consideration of a greater range of possible diagnoses than would be entertained
      at home. In trying rapidly to identify the cause of a presenting illness in the
      traveler, knowledge of their natural history and a carefully taken account of the
      location of the trip undertaken and potential exposure to exotic infections helps
      narrow the range of possibilities and thus the amount of laboratory investigation
      and imaging needed to confirm a diagnosis.

PMID- 22963786
TI  - Travel medicine.

PMID- 22963787
TI  - Problems of capacity, consent and confidentiality.
AB  - For the clinician managing a woman who has been violated sexually, core values of
      compassion, understanding and concern for the woman's distress are essential. The
      nature of the violation itself places the woman in a uniquely dependant, anxious,
      vulnerable and exploitative state. Capacity, consent and confidentiality derive
      from the principle of autonomy. Informed consent entails a process of information
      sharing and decision making based on mutual respect and participation.
      Practitioners should have communication, listening and interpretative skills. One
      of the greatest challenges is the difficulty in ascertaining whether or not the
      woman truly understands and grasps the nature of her condition. There are many
      challenges to obtaining a valid consent in the real world. Information obtained
      from the woman could be shameful and embarrassing, but would be used in a court
      of law. She should be informed of the potential for breach of confidentiality.
      These issues are explored and examples of practical application of the relevant
      themes are given from the England and Wales jurisdiction.

PMID- 22963788
TI  - Velocimetry of red blood cells in microvessels by the dual-slit method: effect of
      velocity gradients.
AB  - The dual-slit is a photometric technique used for the measurement of red blood
      cell (RBC) velocity in microvessels. Two photometric windows (slits) are
      positioned along the vessel. Because the light is modulated by the RBCs flowing
      through the microvessel, a time dependent signal is captured for each window. A
      time delay between the two signals is obtained by temporal cross correlation, and
      is used to deduce a velocity, knowing the distance between the two slits. Despite
      its wide use in the field of microvascular research, the velocity actually
      measured by this technique has not yet been unambiguously related to a relevant
      velocity scale of the flow (e.g. mean or maximal velocity) or to the blood flow
      rate. This is due to a lack of fundamental understanding of the measurement and
      also because such a relationship is crucially dependent on the non-uniform
      velocity distribution of RBCs in the direction parallel to the light beam, which
      is generally unknown. The aim of the present work is to clarify the physical
      significance of the velocity measured by the dual-slit technique. For that
      purpose, dual-slit measurements were performed on computer-generated image
      sequences of RBCs flowing in microvessels, which allowed all the parameters
      related to this technique to be precisely controlled. A parametric study
      determined the range of optimal parameters for the implementation of the dual
      slit technique. In this range, it was shown that, whatever the parameters
      governing the flow, the measured velocity was the maximal RBC velocity found in
      the direction parallel to the light beam. This finding was then verified by
      working with image sequences of flowing RBCs acquired in PDMS micro-systems in
      vitro. Besides confirming the results and physical understanding gained from the
      study with computer generated images, this in vitro study showed that the profile
      of RBC maximal velocity across the channel was blunter than a parabolic profile,
      and exhibited a non-zero sliding velocity at the channel walls. Overall, the
      present work demonstrates the robustness and high accuracy of the optimized dual
      slit technique in various flow conditions, especially at high hematocrit, and
      discusses its potential for applications in vivo.

PMID- 22963789
TI  - Two new class III G6PD variants [G6PD Tunis (c.920A>C: p.307Gln>Pro) and G6PD
      Nefza (c.968T>C: p.323 Leu>Pro)] and overview of the spectrum of mutations in
      Tunisia.
AB  - We screened 423 patients referred to our laboratory after hemolysis triggered by
      fava beans ingestion, neonatal jaundice or drug hemolysis. Others were
      asymptomatic but belonged to a family with a history of G6PD deficiency. The
      determination of enzymatic activity using spectrophotometric method, revealed 293
      deficient (143 males and 150 females). The molecular analysis was performed by a
      combination of PCR-RFLP and DNA sequencing to characterize the mutations causing
      G6PD deficiency. 14 different genotypes have been identified : G6PD A(-)
      (376A>G;202G>A) (46.07%) and G6PD Med (33.10%) were the most common variants
      followed by G6PD Santamaria (5.80%), G6PD Kaiping (3.75%), the association
      [c.1311T and IVS11 93c] (3.75%), G6PD Chatham (2.04%), G6PD Aures (1.70%), G6PD
      A(-) Betica (0.68%), the association [ 376G;c.1311T;IVS11 93c] (0.68%), G6PD
      Malaga, G6PD Canton and G6PD Abeno respectively (0.34%). Two novel missense
      mutations were identified (c.920A>C: p.307Gln>Pro and c.968T>C: p.323 Leu>Pro).
      We designated these two class III variants as G6PD Tunis and G6PD Nefza. A
      mechanism which could account for the defective activity is discussed.

PMID- 22963790
TI  - Comparative study of class 1 integron, ampicillin, chloramphenicol, streptomycin,
      sulfamethoxazole, tetracycline (ACSSuT) and fluoroquinolone resistance in various
      Salmonella serovars from humans and animals.
AB  - A total of 499 Salmonella isolates including 9 serovars from humans and various
      animal hosts were collected to compare prevalence of integron and antimicrobial
      resistance. The integron and gene cassette were detected by PCR, and then the
      gene cassette type was further determined by sequencing and restriction fragment
      length polymorphism (RFLP) analysis. The antimicrobial susceptibility test was
      conducted by disk diffusion method. The positivity percentage of class 1 integron
      and the diversity of gene cassettes carried by integron were quite different in
      various Salmonella serovars, especially comparing those from animals to humans.
      After sequencing and RFLP analysis, it was identified eight gene cassette types.
      The gene cassette type D carrying ampicillin/streptomycin resistance genes was
      the most common one (42.2%) in the integron-positive isolates. More diversity of
      gene cassette types was identified in humans comparing to that in animals.
      Several gene cassette types were identified for the first time in some Salmonella
      serovars. In this study, 31.5% (157/499) of the isolates were multi-resistant to
      ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline
      (ACSSuT). S. Choleraesuis isolates with the cassette type A1, but S. Typhimurium
      isolates with the cassette type E1, were frequently associated with ACSSuT
      resistant (80.6% and 72.7%, respectively). There was a significant association
      between the presence of class 1 integron and quinolone resistance in S.
      Choleraesuis isolates, but not in S. Typhimurium. Our findings imply that
      transmission efficiency of various gene cassettes through the integron could be
      different in various Salmonella serovars.

PMID- 22963791
TI  - Application of metatranscriptomics to soil environments.
AB  - The activities of soil microbial communities are of critical importance to
      terrestrial ecosystem functioning. The mechanisms that determine the interactions
      between soil microorganisms, their environment and neighbouring organisms,
      however, are poorly understood. Due to advances in sequencing technologies, an
      increasing number of metagenomics studies are being conducted on samples from
      diverse environments including soils. This information has not only increased our
      awareness of the functional potential of soil microbial communities, but also
      constitutes powerful reference material for soil metatranscriptomics studies.
      Metatranscriptomics provides a snapshot of transcriptional profiles that
      correspond to discrete populations within a microbial community at the time of
      sampling. This information can indicate the potential activities of complex
      microbial communities and the mechanisms that regulate them. Here we summarise
      the technical challenges for metatranscriptomics applied to soil environments and
      discuss approaches for gaining biologically meaningful insight into these
      datasets.

PMID- 22963792
TI  - Transtympanic balloon dilatation of eustachian tube: a human cadaver pilot study.
AB  - OBJECTIVE: To determine the feasibility and safety of transtympanic balloon
      dilatation of the eustachian tube. METHODS: Transtympanic eustachian tube
      dilatation was performed on six cadaver heads using balloon catheters. Catheters
      were placed in each eustachian tube and the head scanned by computed tomography.
      Randomised, blinded dilatation of one balloon in each head was performed,
      followed again by a second computed tomography scan. The scans were reviewed by a
      neurotologist and neuroradiologist who were blinded to previous treatment, and
      measurable dilatation and incidental damage noted. RESULTS: There was adequate
      placement of the balloon catheter beyond the bony isthmus in 6 of 10 eustachian
      tubes. There was one insufficient catheter placement and three adverse placements
      (one into the petrous carotid canal and two into the vidian canal). Only one
      dilated tube showed a measurable increase in diameter. CONCLUSION: This
      experiment revealed serious safety issues with transtympanic eustachian tube
      dilatation. Therefore, this approach should not be considered feasible at this
      time.

PMID- 22963793
TI  - Improvement of Vitreoscilla hemoglobin function by Bacillus licheformis glutamate
      specific endopeptidase treatment.
AB  - Vitreoscilla hemoglobin (VHb) was widely used in metabolic engineering to improve
      oxygen utilization in the low oxygen environment. It is sometimes necessary to
      remove affinity tags because they may impede functions of target proteins. Here
      we report an efficient method employing Glutamate-specific endopeptidase from
      Bacillus licheformis (GSE-BL) to perform the cleavage between VHb and His-tag.
      The optimal length of GSE-BL treatment was 15min. Results of SDS-PAGE and western
      blot demonstrated that the His-tag of VHb-His(6) was nearly completely removed,
      the purity of VHb was enhanced from 74% to 99.5%, and the yield of tagless VHb
      from VHb-His(6) was 92.2%. Results of CO difference spectrum suggested that
      tagless VHb was more prone to bind to CO compared with VHb-His(6). It was
      observed that tagless VHb displayed higher catalase activity than VHb-His(6). The
      enhancement of welan gum yield was more significant by addition of tagless VHb
      compared with addition of VHb-His(6). This method can be utilized to mass-produce
      tagless VHb, thus widening the application of VHb in various industries.

PMID- 22963794
TI  - Expression and purification of the membrane enzyme selenoprotein K.
AB  - Selenoprotein K (SelK) is a membrane protein residing in the endoplasmic
      reticulum. The function of SelK is mostly unknown; however, it has been shown to
      participate in anti-oxidant defense, calcium regulation and in the endoplasmic
      reticulum associated protein degradation (ERAD) pathway. In order to study the
      function of SelK and the role of selenocysteine in catalysis, we have tested
      heterologous expression of human SelK in E. coli. Consequently, we have developed
      an over-expression strategy that exploits the maltose binding protein as a fusion
      partner to stabilize and solubilize SelK. The fusion partner can be cleaved from
      SelK in the presence of a variety of detergents compatible with structural
      characterization and the protein purified to homogeneity. SelK acquires a helical
      secondary structure in detergent micelles, even though it was predicted to be an
      intrinsically disordered protein due to its high percentage of polar residues.
      The same strategy was successfully applied to preparation of SelK binding partner
      - selenoprotein S (SelS). Hence, this heterologous expression and purification
      strategy can be applied to other members of the membrane enzyme family to which
      SelK belongs.

PMID- 22963795
TI  - Detergent selection for enhanced extraction of membrane proteins.
AB  - Generating stable conditions for membrane proteins after extraction from their
      lipid bilayer environment is essential for subsequent characterization.
      Detergents are the most widely used means to obtain this stable environment;
      however, different types of membrane proteins have been found to require
      detergents with varying properties for optimal extraction efficiency and
      stability after extraction. The extraction profiles of several detergent types
      have been examined for membranes isolated from bacteria and yeast, and for a set
      of recombinant target proteins. The extraction efficiencies of these detergents
      increase at higher concentrations, and were shown to correlate with their
      respective CMC values. Two alkyl sugar detergents, octyl-beta-d-glucoside (OG)
      and 5-cyclohexyl-1-pentyl-beta-d-maltoside (Cymal-5), and a zwitterionic
      surfactant, N-decylphosphocholine (Fos-choline-10), were generally effective in
      the extraction of a broad range of membrane proteins. However, certain detergents
      were more effective than others in the extraction of specific classes of integral
      membrane proteins, offering guidelines for initial detergent selection. The
      differences in extraction efficiencies among this small set of detergents
      supports the value of detergent screening and optimization to increase the yields
      of targeted membrane proteins.

PMID- 22963796
TI  - Sparseness of coding in area 17 of the cat visual cortex: a comparison between
      pinwheel centres and orientation domains.
AB  - Optical imaging of intrinsic signals across the primary visual cortex in mammals
      has shown that neurons tuned to the same stimulus orientation are clustered
      together to form orientation domains, which converge on singularities called
      pinwheel centres. We used a combination of two gratings in different mutual
      relationships as in a plaid to study how visual cortical neurons differ in
      integrating these signals. Neurons in the centres of orientation domains
      responded to a smaller range of such composite stimuli than cells near pinwheel
      centres, even though orientation tuning for a single bar or grating did not
      differ significantly between the two locations. We believe that this difference
      between the two locations is related to the way local intracortical interactions
      generate a full complement of orientation preferences from a limited number of
      preferred stimulus orientations represented in the geniculate afferents to the
      striate cortex.

PMID- 22963797
TI  - Neural progenitor cells generate motoneuron-like cells to form functional
      connections with target muscles after transplantation into the musculocutaneous
      nerve.
AB  - Neural progenitor cells (NPCs) are suggested to be a valuable source of cell
      transplant in treatment of various neurological diseases because of their
      distinct attributes. They can be expanded and induced to differentiate in vitro.
      However, it remains uncertain whether in vitro expanded  NPCs have the capacity
      to give rise to functional motoneurons after transplantation in vivo. Here, we
      showed that in vitro expanded NPCs, when transplanted into the musculocutaneous
      nerve, generated motoneuron-like cells that exhibited typical morphology with
      large cell bodies, expressed specific  molecules, and extended axons to form
      functional connections with the target muscle. In contrast, transplanted NPCs
      failed to yield motoneurons in the injured ventral horn of the spinal cord. The
      results of the study demonstrate that NPCs have the potential to generate
      functional motoneurons  in an appropriate environment. The distinct
      differentiating fate of NPCs in the musculocutaneous nerve and the injured
      ventral horn suggests the importance and necessity of modifying the host
      microenvironment in use of NPCs for cell replacement therapies for motoneuron
      diseases.

PMID- 22963798
TI  - Cystic lymphangioma of the kidney: Diagnosis and management.
AB  - INTRODUCTION: Cystic lymphangioma is a rare benign vascular tumor that may arise
      in various sites, revealed at any age. Abdominal locations represent less than
      10% of the cases preferentially involving the mesentery. We report a case of
      primary lymphangioma arising from the kidney. PRESENTATION OF CASE: A 50-year-old
      woman was admitted for severe left lumbar pain. Abdominal ultrasonography and
      computed tomography revealed a 6*10 cm multiloculated cystic mass with
      hydronephrosis, extending along the left renal hilum. Surgical exploration
      revealed a retroperitoneal cystic tumor. Anatomopathologic examination concluded
      it to be a cystic lymphangioma. DISCUSSION: The cystic lymphangioma is a benign
      malformative tumor of the lymphatic system. Surgery is the best curative
      treatment with complete excision, the prognosis is excellent. CONCLUSION: Primary
      renal lymphangioma is exceedingly rare. Medical imaging has certain limits for
      the diagnosis which required histological confirmation. The treatment of choice
      is surgical.

PMID- 22963799
TI  - Isolated and complete traumatic rupture of the pancreas: A case report and a
      review of the literature.
AB  - INTRODUCTION: Pancreatic trauma without injuries to other organs is uncommon, as
      reported in the reviewed literature. Diagnosis of pancreatic trauma might be
      difficult, due to unspecific signs and symptoms. The integrity of the main
      pancreatic duct is the crucial point in the management and outcome of patients
      with pancreatic trauma. PRESENTATION OF CASE: The authors report a case of
      delayed diagnosis after a complete traumatic rupture of the main pancreatic duct,
      successfully managed by surgical treatment. The authors performed a laparotomy
      with complete removal of necrotic pancreatic tissue at the site of rupture. The
      proximal pancreatic stump was hand-sewn with detached stitches and a disposable
      catheter was positioned into Wirsung's duct, a diversion of the distal stump with
      a Roux-en-y pancreato-jejunal anastomosis was performed. The postoperative course
      was uneventful. DISCUSSION: Traumatic injuries of the pancreas occur after blunt
      abdominal traumas or penetrating wounds with a ratio of 3:1. Isolated traumatic
      injuries of the pancreas are uncommon; and they are usually associated with
      injuries to other organs. Surgical solutions for the treatment of pancreas
      lesions vary and it is well known that a surgical procedure performed after a
      delayed diagnosis is associated with high mortality and morbidity, especially in
      pancreatic duct rupture. CONCLUSION: Pancreatic trauma is a diagnostic and
      therapeutic challenge for the trauma surgeon. The integrity of the main
      pancreatic duct is the most important determinant of outcome after injury to the
      pancreas and, in Wirsung's duct rupture, early surgery may improve it.

PMID- 22963800
TI  - Safety of ZostavaxTM--a cohort study in a managed care organization.
AB  - BACKGROUND: ZostavaxTM is a live, attenuated varicella-zoster virus vaccine
      indicated for the prevention of herpes zoster (shingles). An observational post
      licensure (Phase IV) study was conducted at Kaiser Permanente Northern California
      (KPNC), a US managed care organization, to assess the safety of zoster vaccine in
      people 60 years of age or older, vaccinated in routine medical care. METHODS: We
      performed a cohort study, comparing rates of clinical events resulting in
      hospitalizations or emergency department visits in a 42-day risk time period
      immediately following vaccination with rates in the same cohort in a subsequent
      comparison time period. The study data were reviewed and interpreted by an
      external safety review committee of 3 independent experts. RESULTS: Approximately
      29,000 people >= 60 years of age were vaccinated with zoster vaccine from July
      2006 to November 2007. Of the 386 comparisons performed for the main analysis, 4
      had an increased relative risk with a nominal p-value <= 0.05. After medical
      records review, the timing of these conditions and procedures was found to be
      often prior to vaccination, and no clear increase in health events was observed
      in the risk period following vaccination compared to later. Persons receiving
      zoster vaccine appeared to be in their optimal health at the time of vaccination,
      which led to an apparent protective effect of the vaccine for some health
      outcomes, due to the study design. CONCLUSIONS: There was no evidence of a safety
      concern for zoster vaccine.

PMID- 22963801
TI  - Efficacy of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical,
      virological, pathological and immunological examination under field conditions.
AB  - Inactivated chimeric porcine circovirus (PCV) 1-2 vaccine was initially taken off
      the market due to concerns that the vaccine virus was not killed and thus further
      replicated and spread in the pig population. In August 2011, a reformulated
      inactivated chimeric PCV1-2 vaccine re-entered the market. The efficacy of the
      reformulated inactivated chimeric PCV1-2 vaccine was evaluated under field
      conditions for registration as recommended by the Republic of Korea's Animal,
      Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based
      on their history of postweaning multisystemic wasting syndrome (PMWS). On each
      farm, a total of 50 3-week-old pigs were randomly allocated to one of two
      treatment groups: (i) vaccinated at 3 weeks of age and (ii) non-vaccinated.
      Clinical examination indicated that vaccinated animals displayed an improved
      average daily weight gain (672.2g/day vs. 625g/day; difference of +47.3g/day;
      P<0.05) and a reduced time to market (177 days vs. 183 days; difference of -6
      days; P<0.05). Virological examination indicated that vaccinated animals
      displayed a reduced PCV2 load in the blood and nasal swabs compared to non
      vaccinated animals. Pathological examination indicated that vaccination of pigs
      against PCV2 effectively reduced the number of PMWS-associated microscopic
      lesions and the PCV2 load in lymphoid tissues compared to non-vaccinated animals
      in the 3 herds. Immunological examination indicated that vaccinated animals
      induced PCV2-specific neutralizing antibodies (NA) and interferon-gamma-secreting
      cells (IFN-gamma-SCs). A reduction in the PCV2 load in the blood coincided with
      the appearance of both PCV2-specific NA and IFN-gamma-SCs in the vaccinated
      animals. The number of CD4(+) cells was decreased in non-vaccinated animals
      compared to vaccinated animals. The reformulated inactivated chimeric PCV1-2
      vaccine seems to be very effective in controlling PCV2 infection based on
      clinical, virological, pathological, and immunological evaluations under field
      conditions.

PMID- 22963802
TI  - Correction of the information presented as reference.

PMID- 22963803
TI  - Probing the protective effects of a conformationally constrained nicotine
      vaccine.
AB  - Despite being consistently ranked as the leading cause of preventable death in
      the United States, about 20% of the population continues to smoke. Current
      smoking cessation therapies offer limited success, show high rates of relapse,
      and have potentially dangerous side effects, consequently emphasizing the need
      for alternative therapies. Immunopharmacotherapy aims to use highly specific
      antibodies to sequester nicotine in the bloodstream thus blunting passage into
      the brain and minimizing positive reinforcing effects. A successful vaccination
      strategy is dependent upon the appropriate hapten design, carrier protein and
      adjuvant which affect both the magnitude and affinity of the immune response
      elicited. Our laboratory previously demonstrated the use of molecular constraint
      as a means to increase the intrinsic immunogenicity and antigenicity of a
      nicotine vaccine. The present study expands upon those initial results and
      explores the protective effects of vaccination with both constrained hapten CNI
      and its unconstrained counterpart NIC. Our results demonstrate how immunization
      with CNI-KLH produces large amounts of moderate affinity anti-nicotine antibodies
      even when formulated with ALUM adjuvant, making it particularly relevant for
      human use. In contrast, vaccination with NIC-KLH produced moderate amounts of
      high affinity anti-nicotine antibodies. These differential responses proved
      critical in offering protecting effects. Vaccination with CNI, but not NIC,
      resulted in an increase of self-administration responding on a progressive ratio
      schedule using a high nicotine dose (0.03 mg/kg/infusion; ~ 2 cigarettes in
      human) as compared to KLH-controls. Furthermore, vaccination with CNI was able to
      antagonize the analgesic effects of a heavy bolus dose of nicotine (0.35 mg/kg).
      These results support our hypothesis that molecular constraint can be
      advantageously utilized to increase the immunogenicity of a nicotine vaccine.
      Furthermore in correlating the behavioral effects with the differential responses
      elicited, we shed light on the distinct roles of antibody concentration and
      affinity.

PMID- 22963804
TI  - Estimated size of the population at risk of severe adverse events after smallpox
      vaccination in Israel.
AB  - BACKGROUND: The population at risk of adverse events after smallpox vaccination
      has increased in recent years. This has important implications for preparedness
      strategies against bioterrorism with the variola virus. The aim of the study was
      to estimate the size of this special population in Israel. METHODS: The study was
      conducted in January 2010. Data on patients with contraindications to smallpox
      vaccination, as delineated by the Israel Ministry of Health for planning post
      event strategies, were retrieved from the computerized records of the Department
      of AIDS and Tuberculosis and the Transplantation Center of the Israel Ministry of
      Health. In addition, the database of the main Health Maintenance Organization in
      Israel which insures 60% of the national population was searched using ICD-9
      codes and specific medications issued in the last quarter of 2009. RESULTS: Of
      the 7,563,800 persons residing in Israel in January 2010, 326,318 were at risk of
      an adverse event after smallpox vaccination. CONCLUSION: Approximately 4.3% of
      the Israeli population should not be exposed to the currently used smallpox
      vaccine. This knowledge is important to ensure the effectiveness of mass
      vaccination programs in the event of a bioterror attack.

PMID- 22963805
TI  - [Alveolar hemorrhage].
AB  - Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells
      originating from the lung capillaries or venules within the alveoli. The
      diagnosis is established on clinical features, radiological pattern, and
      especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many
      immune or non-immune causes. Immune causes of DAH include vasculitides,
      connective tissue diseases, especially systemic lupus erythematosus, and
      antiglomerular basement membrane antibody disease (Goodpasture's syndrome).
      Treatment is both supportive and causal, often based on high dose corticosteroids
      and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma
      exchanges are performed in antiglomerular basement membrane antibody disease and
      systemic lupus erythematosus, and are considered in systemic vasculitis. Non
      immune causes of DAH mainly include heart diseases, coagulation disorders,
      infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is
      that of its cause. Whatever the cause, DAH is an emergency requiring prompt
      assessment and early treatment.

PMID- 22963806
TI  - CD4(+)CD28(null) T lymphocyte frequency, a new marker of cardiovascular risk:
      relationship with polycystic ovary syndrome phenotypes.
AB  - OBJECTIVE: To study the frequency of CD4(+)CD28(null) T cells, which are
      aggressive T lymphocytes associated with recurrent coronary instability and type
      2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and
      in age- and body mass index-matched healthy women. DESIGN: Retrospective cohort
      observational study. SETTING: Unit of human reproductive pathophysiology,
      university hospital. PATIENT(S): A total of 167 PCOS patients and 102 control
      subjects. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CD4(+)CD28(null) T cell
      frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic
      parameters. RESULT(S): CD4(+)CD28(null) frequency was significantly higher in all
      PCOS groups than in control subjects. CD4(+)CD28(null) frequency was
      significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2-7.1) than
      in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary
      (PCO) (3.5%, range 1-5.8), H + O (3%, range 1.8-4.7), and H + PCO (2.63%, range
      1.2-4.1). The relative risk of non-H phenotype for PCOS women in the highest
      quartile for CD4(+)CD28(null) frequency compared with PCOS women with the lowest
      quartile was 3.2 (95% confidence interval 1.9-5.8). CONCLUSION(S): Cardiovascular
      risk evaluation should be performed in all PCOS phenotypes. In particular, we
      demonstrated that the non-H phenotype has potentially increased cardiovascular
      risk in terms of CD4(+)CD28(null) frequency.

PMID- 22963807
TI  - Acute portal vein thrombosis complicating in vitro fertilization.
AB  - OBJECTIVE: To describe a case of acute portal vein thrombosis after IVF
      treatment. DESIGN: Case report. SETTING: University teaching hospital.
      PATIENT(S): A 39-year-old woman experienced worsening, right upper quadrant pain
      several days after oocyte retrieval; ET was withheld. Imaging studies revealed
      acute portal vein thrombosis with extension into the splenic and superior
      mesenteric veins. INTERVENTION(S): Therapeutic anticoagulation; no ET was
      performed. MAIN OUTCOME MEASURE(S): Improvement in symptoms, accurate diagnosis
      of condition. RESULT(S): Decreased size of portal vein thrombosis and partial
      vessel recanalization. CONCLUSION(S): Thromboembolic events are a rare
      complication of assisted reproductive technology (ART). In women who present with
      upper abdominal pain during ART, portal vein thrombosis should be considered in
      the differential diagnosis.

PMID- 22963808
TI  - Aromatase inhibitor treatment of menorrhagia and subsequent pregnancy in a
      patient with familial hyperparathyroidism-jaw tumor syndrome.
AB  - OBJECTIVE: To describe the clinical management of menorrhagia in a woman with
      hyperparathyroidism-jaw tumor syndrome (HPT-JT). DESIGN: Case report. SETTING:
      Large translation research hospital. PATIENT(S): A 26-year-old nulligravid woman
      with familial HPT-JT presented with life-long menorrhagia resistant to
      progesterone intrauterine device (IUD) therapy and a desire for fertility.
      INTERVENTION(S): Aromatase inhibitor therapy. MAIN OUTCOME MEASURE(S): Clinical
      response to therapy and pregnancy. RESULT(S): Imaging demonstrated an enlarged
      endometrial lining and thickening of the junctional zone. At operative
      hysteroscopy, multiple atypical endometrial polyp-like lesions filled the entire
      uterine cavity and were removed. Histologic evaluation demonstrated the lesions
      to be adenomyomas with an abundance of aromatase expression. Postoperative
      treatment included an aromatase inhibitor. The patient's menorrhagia, which had
      previously been resistant to progesterone IUD therapy, resolved with the
      aromatase inhibitor. After 10 months of this treatment, the aromatase inhibitor
      was discontinued and a repeated hysteroscopy revealed a markedly improved uterine
      cavity. The patient subsequently became pregnant on her first natural cycle and
      delivered a healthy term infant. CONCLUSION(S): Aromatase inhibitors may
      represent a novel treatment for benign uterine pathology in HPT-JT.

PMID- 22963809
TI  - Development and characterization of an endometrial tissue culture model for study
      of early implantation events.
AB  - OBJECTIVE: To improve and characterize an endometrial tissue culture model.
      DESIGN: Experimental study of the characteristics of mouse endometrial tissue
      cultured on amniotic membrane matrix. SETTING: University research laboratory.
      ANIMAL(S): Sexually mature female ICR mice. INTERVENTION(S): Histologic
      examination of the cultured endometrial tissues. The attachment rates of the
      cultured tissues to implantation blastocysts under various conditions were
      determined. MAIN OUTCOME MEASURE(S): Morphometric analysis of the cultured
      tissues. Blastocyst attachment rate and expression of decidualization markers
      cylcooxygenase-2, connexin 43, and peroxisome proliferator-activated receptor
      delta. RESULT(S): Endometrial tissues could be grown on amniotic membrane matrix
      for 3 days with morphometric parameters similar to those in the in vivo
      pseudopregnant control. The cultured tissues responded to the surrounding steroid
      environment. Morphometric assessment indicated that medium containing 63.5 nmol/L
      P and 0.9 nmol/L E(2) provided the best support. The condition allowed attachment
      of approximately 60% of the cocultured blastocysts. A small percentage of the
      attached blastocyst started to penetrate the luminal epithelium within 28 hours.
      The attachment rate was significantly reduced with prior treatment of the
      cultured endometrium with anti-leukemia inhibitory factor antibody. The attached
      blastocyst induced decidualization around the attachment site. CONCLUSION(S): The
      model is useful for the study on implantation in the mouse.

PMID- 22963810
TI  - MicroRNA-1 inhibits proliferation of hepatocarcinoma cells by targeting
      endothelin-1.
AB  - AIMS: MicroRNA-1 (miR-1) has been demonstrated as a tumor-suppressive miRNA,
      which shows a down-regulated pattern in several human malignancies including
      hepatocellular carcinoma (HCC). However, the pathophysiologic roles of miR-1 and
      their mechanisms in HCC tumorigenesis are still not totally elucidated. MAIN
      METHODS: Pre-miR-1 was cloned into pSuper plasmid to overexpress the miR-1 in
      hepatoma cells. Real-time PCR and Western blot were applied to detect miR-1, ET-1
      mRNA and protein levels respectively. Dual luciferase reporter assay was
      conducted to investigate the binding site of miR-1 on 3'UTR of ET-1 mRNA.
      Proliferation of hepatoma cells was evaluated by MTT assay. KEY FINDINGS: We
      observed that over-expression of miR-1 by miRNA-expressing plasmid transfection
      in HepG2 and Hep3B cells significantly reduced the proliferation of these cells.
      To explore the mechanism, we examined the potential target genes of miR-1 by
      bioinformatics. A potent mitogen, Endothelin-1 (ET-1), attracted our attention.
      Elevated expression of ET-1 but reduced miR-1 level was detected both in human
      liver cancer tissues and in hepatoma cell lines using Western Blot and miRNA real
      time PCR respectively. By the over-expression and inhibition of miR-1 in HepG2
      and Hep3B, we confirmed that miR-1 negatively regulated ET-1 expression in
      hepatoma cells. A luciferase reporter assay showed that miR-1 regulation was
      established by pairing to a complementary binding site within the ET-1 3'UTR.
      Finally, attenuated proliferation of hepatoma cells by over-expression of miR-1
      could be partially restored by exogenous ET-1 treatment. SIGNIFICANCE: Our
      findings demonstrate that miR-1 could inhibit ET-1 expression to attenuate the
      proliferation of hepatoma cells.

PMID- 22963811
TI  - Computed tomography angiography-based evaluation of great saphenous vein conduit
      for lower extremity bypass.
AB  - OBJECTIVE: Lower extremity computed tomography angiography (CTA) is frequently
      used for anatomic assessment of lower extremity peripheral arterial disease. When
      lower extremity bypass is planned, duplex ultrasound (DUS) is routinely obtained
      to evaluate the great saphenous vein (GSV) for use as conduit. Although GSV can
      be visualized on CTA images, diameter assessment is not routinely included in
      formal study interpretation. We hypothesized that CTA images could be used to
      measure GSV diameters and that CTA-based diameters would correlate with
      measurements obtained using DUS. METHODS: Consecutive patients undergoing lower
      extremity arterial bypass who were evaluated preoperatively with both CTA and DUS
      vein mapping were identified at a single hospital. Minimum above- and below-knee
      GSV diameters were measured from electronically archived CTA images by two
      independent observers. CTAs were performed using standard arterial phase protocol
      without additional venous phase imaging. Between-observer reproducibility of CTA
      based diameter measurements was evaluated using intraclass correlation
      coefficients. Correlation between CTA and DUS-based GSV diameters was evaluated
      with Spearman correlation coefficients. CTA diameter cut-points for
      identification of adequate GSV bypass conduit, defined as DUS-based minimum GSV
      diameter>=3 mm, were determined using receiver-operating characteristic curves.
      RESULTS: Sixty-three lower extremities were evaluated in 36 patients. In the
      absence of previous surgical removal, GSV was visible on all CTAs reviewed. No
      instances of GSV thrombosis were identified on DUS. Minimum DUS-based above-knee
      GSV diameter was 2.9+/-0.1 mm (range, 1.4-4.6 mm), and mean below-knee diameter
      was 2.6+/-0.1 mm (range, 1.3-4.0 mm). When GSV was visible and exceeded the
      minimum diameter threshold for CTA measurement, correlation between CTA- and DUS
      based diameters was both positive and highly significant (rho=0.595; P<.0001).
      CTA-based diameters also had excellent reliability between observers (r [95% CI]:
      0.88 [0.85-0.91]). For identification of adequate bypass conduit using CTA, above
      knee GSV diameter>=3.9 mm was 67% sensitive and 73% specific; below-knee GSV
      diameter>=3.0 mm was 75% sensitive and 84% specific. CONCLUSIONS: CTA-based GSV
      diameter measurements have good reproducibility and highly significant
      correlation with DUS-based diameters. CTA-based GSV diameter is a specific but
      relatively insensitive indicator of adequate bypass conduit. When CTA-based
      diameters indicate inadequate GSV bypass conduit, confirmatory DUS vein mapping
      is warranted. Confirmatory DUS vein mapping may be unnecessary when adequate vein
      diameter is identified on CTA.

PMID- 22963813
TI  - A hybrid approach to recanalization of a chronic iliofemoral occlusion.
AB  - The Viabahn covered stent (W. L. Gore and Associates Inc, Flagstaff, Ariz) is
      made of expanded polytetrafluoroethylene attached to an external nitinol stent
      and is primarily used in the endovascular treatment of lower extremity arterial
      occlusive disease. The use of this device as an open conduit for lower extremity
      revascularization has been rarely reported. We expand on this experience by
      presenting a case of hybrid endovascular and open iliofemoral bypass in which we
      used the Viabahn endoprosthesis to recanalize an occluded iliac artery, followed
      by direct suturing of the distal portion of the Viabahn stent graft to the native
      common femoral artery bifurcation.

PMID- 22963812
TI  - Effect on walking distance and atherosclerosis progression of a nitric oxide
      donating agent in intermittent claudication.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is almost invariably associated
      with a generalized atherosclerotic involvement of the arterial tree and
      endothelial dysfunction. Previous short-term studies showed improvement of
      vascular reactivity and walking capacity in PAD patients by measures aimed at
      restoring nitric oxide (NO) production. NO is also known to prevent the
      progression of atherosclerosis. We wished to assess whether the prolonged
      administration of an NO-donating agent (NCX 4016) improves the functional
      capacity of PAD patients and affects the progression of atherosclerosis as
      assessed by carotid intima-media thickness (IMT). METHODS: This prospective,
      double-blind, placebo-controlled study enrolled 442 patients with stable
      intermittent claudication who were randomized to NCX 4016 (800 mg, twice daily)
      or its placebo for 6 months. The primary study outcome was the absolute
      claudication distance on a constant treadmill test (10% incline, 3 km/h). The
      main secondary end point was the change of the mean far-wall right common carotid
      artery IMT. RESULTS: The increase of absolute claudication distance at 6 months
      compared with baseline was 126+/-140 meters in the placebo-treated group and
      117+/-137 meters in the NCX 4016-treated group, with no significant differences.
      Carotid IMT increased in the placebo-treated group (+0.01+/-0.01 mm; P=.55) and
      decreased in the NCX 4016-treated group (-0.03+/-0.01 mm; P=.0306). Other
      secondary end points did not differ between the two treatments. CONCLUSIONS: Long
      term NO donation does not improve the claudication distance but does reduce
      progression of atherosclerosis in patients with PAD. Further studies aimed at
      assessing whether long-term NO donation may prevent ischemic cardiovascular
      events are warranted.

PMID- 22963815
TI  - The effect of risk and race on lower extremity amputations among Medicare
      diabetic patients.
AB  - OBJECTIVE: The effect of national quality initiatives aiming at limiting lower
      extremity amputations in diabetic patients remains uncertain. We therefore
      explored trends in amputation among Medicare diabetic patients with a focus on
      those at highest risk. METHODS: The Diabetes Analytical File, an enhanced sample
      of all diabetic patients from the Medicare 5% sample, was used to study the
      national incidence of amputation in diabetic patients. Within a cohort of ~5
      million diabetic patients between 1999 and 2006, we compared the incidence of
      amputation in high-risk (end-stage renal disease or more than three
      comorbidities) and low-risk groups and by race. RESULTS: Between 1999 and 2006,
      23,976 amputations were performed, comprising 11,558 in high-risk and 12,418 in
      low-risk patients. The amputation rate declined over time from 4.8/1000 in 1999
      to 4.4/1000 in 2006 (P<.001). High-risk patients represented a growing proportion
      of all amputations (33% in 1999, 50% in 2006; P<.001) despite representing 4% of
      diabetic patients in 1999 and 10% in 2006 (P<.001). The incidence of amputation
      was 29.6/1000 in the high-risk group vs 2.7/1000 in low-risk patients (P<.001).
      African Americans had higher rates of amputation in high-risk and low-risk
      groups. CONCLUSIONS: High-risk patients represent a minority of Medicare diabetic
      patients but account for 50% of all amputations, and this effect is magnified in
      African Americans. Future quality improvement efforts should focus on high-risk
      patients and African Americans.

PMID- 22963816
TI  - Chronicity of depressive problems and the cortisol response to psychosocial
      stress in adolescents: the TRAILS study.
AB  - Clinical and epidemiological studies, further supported by meta-analytic studies,
      indicate a possible association between chronicity (i.e., persistence or
      recurrence) of depression and hypothalamic-pituitary-adrenal (HPA) axis
      responsiveness to psychosocial stress. In the present study, we examined whether
      and how chronicity of depressive problems predicts cortisol responses to a
      standardized social stress test in adolescents. Data were collected in a high
      risk focus sample (n=351) of the Tracking Adolescents' Individual Lives Survey
      (TRAILS) cohort, a large prospective population study with bi- to triennial
      measurements. Depressive problems were assessed around age 11, 13.5, and 16.
      Cortisol levels were measured in saliva, sampled before, during, and after the
      Groningen Social Stress Test (GSST), to determine the cortisol response to
      psychosocial stress. The area under the curve with respect to the increase (AUCi)
      (i.e., change from baseline) of the cortisol response was used as a measure of
      HPA axis response. By means of linear regression analysis and repeated-measures
      analysis of variance, it was examined whether chronicity of depressive problems
      predicted the cortisol response to the GSST around the age of 16. Chronicity of
      depressive problems was significantly associated with cortisol stress responses.
      The relationship was curvilinear, with recent-onset depressive problems
      predicting an increased cortisol response, and more chronic depressive problems a
      blunted response. The results of this study suggest that depressive problems
      initially increase cortisol responses to stress, but that this pattern reverses
      when depressive problems persist over prolonged periods of time.

PMID- 22963817
TI  - Predicting success of metabolic surgery: age, body mass index, C-peptide, and
      duration score.
AB  - BACKGROUND: Surgery is the most effective treatment of morbid obesity and leads
      to dramatic improvements in type 2 diabetes mellitus (T2DM). Gastrointestinal
      metabolic surgery has been proposed as a treatment option for T2DM. However, a
      grading system to categorize and predict the outcome of metabolic surgery is
      lacking. The study setting was a tertiary referral hospital (Taoyuan City,
      Taoyuan County, Taiwan). METHODS: We first evaluated 63 patients and identified 4
      factors that predicted the success of T2DM remission after bariatric surgery in
      this cohort: body mass index, C-peptide level, T2DM duration, and patient age. We
      used these variables to construct the Diabetes Surgery Score, a multidimensional
      10-point scale along which greater scores indicate a better chance of T2DM
      remission. We then validated the index in a prospective collected cohort of 176
      patients, using remission of T2DM at 1 year after surgery as the outcome
      variable. RESULTS: A total of 48 T2DM remissions occurred among the 63 patients
      and 115 remissions (65.3%) in the validation cohort. Patients with T2DM remission
      after surgery had a greater Diabetes Surgery Score than those without (8 +/- 4
      versus 4 +/- 4, P < .05). Patients with a greater Diabetes Surgery Score also had
      a greater rate of success with T2DM remission (from 33% at score 0 to 100% at
      score 10); A 1-point increase in the Diabetes Surgery Score translated to an
      absolute 6.7% in the success rate. CONCLUSION: The Diabetes Surgery Score is a
      simple multidimensional grading system that can predict the success of T2DM
      treatment using bariatric surgery among patients with inadequately controlled
      T2DM.

PMID- 22963818
TI  - Factor structure and predictive utility of the Binge Eating Scale in bariatric
      surgery candidates.
AB  - BACKGROUND: Screening for binge eating before bariatric surgery is a component of
      the recommended clinical practice for bariatric surgery candidates. The Binge
      Eating Scale (BES) is 1 of the most commonly used self-report measures of eating
      behaviors in preoperative evaluations; however, the factor structure of this
      measure has not been evaluated in the bariatric population. The aims of the
      present study were to report the mean, standard deviation, and reliability of the
      BES for patients seeking bariatric surgery; to evaluate the 2-factor structure of
      the BES using confirmatory factor analysis; and to investigate the association
      between the BES and its factors with surgical weight loss. The setting was an
      academic medical center. METHODS: A total of 530 patients completed the BES as a
      component of their psychological evaluation before undergoing Roux-en-Y gastric
      bypass surgery. RESULTS: Approximately one third of patients reported at least
      mild to moderate binge eating, with 9% of patients reporting severe binge eating
      on the BES. The BES demonstrated good internal consistency. The results of the
      confirmatory factor analysis indicated that a 2-factor structure, consisting of
      feelings/cognitions related to binge eating and behavioral manifestations of
      binge eating, was the best fit to the data. Nonsignificant correlations were
      found between the BES and its 2 factors with short-term postoperative weight
      loss. CONCLUSION: The BES measures 2 aspects of binge eating in bariatric surgery
      candidates, feelings/cognitions and behavioral manifestations of binge eating.
      Consideration of these factors in patients presenting for bariatric surgery could
      allow for a more detailed understanding of binge eating in this population.

PMID- 22963819
TI  - Adding chemoprophylaxis to sequential compression might not reduce risk of venous
      thromboembolism in bariatric surgery patients.
AB  - BACKGROUND: Anticoagulation, the use of sequential compression devices on the
      lower extremities perioperatively, and early ambulation are thought to reduce the
      incidence of venous thromboembolism (VTE) postoperatively and are recommended to
      reduce VTE risk. However, the evidence on which this recommendation has been
      based is not particularly strong. We have demonstrated that even a large,
      multicenter cohort with carefully collected prospective data is inadequate to
      provide sufficient evidence to support, or refute, this recommendation. METHODS:
      Longitudinal Assessment of Bariatric Surgery participants from 10 centers in the
      United States who underwent their first bariatric surgery between March 2005 and
      December 2007 constituted the study group. We examined the ability to address the
      question of whether anticoagulation therapy, in addition to sequential
      compression, reduces the 30-day incidence of VTE or death sufficiently to
      recommend the use of prophylactic anticoagulation, a therapy that is not without
      risk. RESULTS: Of 4416 patients, 396 (9.0%) received sequential compression
      alone, and 4020 also received anticoagulation therapy. The incidence of VTE
      within 30 days of surgery was low (.25% among those receiving sequential
      compression alone and .47% when anticoagulation therapy was added), and the 30
      day incidence of death was also low (.25% versus .34%, respectively, P = .76, for
      sequential compression alone versus sequential compression plus anticoagulation
      therapy). Estimates of the number of cases required to address the question of
      whether a difference exists in the outcome related to VTE chemoprophylaxis or
      whether the outcome rates are equivalent have ranged from 13,680 to >= 35,760
      patients, depending on whether superiority or equivalence was being analyzed.
      CONCLUSION: Sufficient evidence from a clinical trial study to determine whether
      prophylactic anticoagulation added to compression devices further prevents VTE is
      not available, and such a trial is likely to be impractical. The data presented
      are insufficient to make a final recommendation concerning prophylactic treatment
      to prevent VTE in the 30 days after bariatric surgery.

PMID- 22963820
TI  - Single-anastomosis duodenoileal bypass with sleeve gastrectomy: metabolic
      improvement and weight loss in first 100 patients.
AB  - BACKGROUND: Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a
      simplified 1-loop duodenal switch with a 200-250 common channel. Our objective
      was to analyze the weight loss and metabolic results of the technique on a series
      of 100 consecutively operated patients at a tertiary center university hospital.
      METHODS: A total of 100 patients consecutively underwent surgery. The criteria of
      inclusion were morbid obesity or metabolic disease. In the first 50 cases, the
      common/efferent limb measured 200 cm. The length was changed to 250 cm to reduce
      the hypoproteinemia rate. RESULTS: No mortality and no severe complications
      developed. The mean excess weight loss was >95% maintained during the follow-up
      period. More than 90% of the patients experimented complete remission of type 2
      diabetes mellitus. Two conversions to a standard duodenal switch with a longer
      alimentary channel were required because of recurrent hypoproteinemia.
      Hypertension was controlled in 98% of the patients, with a 58% remission rate.
      The mean number of bowel movements was 2.5/d. CONCLUSION: Single-anastomosis
      duodenoileal bypass with sleeve gastrectomy is a simplified duodenal switch
      procedure that is safe and quicker to perform and offers good results for the
      treatment of both morbid obesity and its metabolic complications.

PMID- 22963821
TI  - Small bowel infarction after herniation through gastric band tubing loop.

PMID- 22963822
TI  - Laparoscopic longitudinal gastrectomy and duodenojejunostomy for treatment of
      diabetic gastroparesis.

PMID- 22963823
TI  - MicroRNA-467b targets LPL gene in RAW 264.7 macrophages and attenuates lipid
      accumulation and proinflammatory cytokine secretion.
AB  - LPL (lipoprotein lipase) is a rate-limiting enzyme involved in the hydrolysis of
      triglycerides. Previous studies have shown that microRNA (miR)-467b regulates
      hepatic LPL expression and plays a role in the progression of steatosis or
      abnormal lipid retention in obese mice. Macrophage-derived LPL has been shown to
      promote atherosclerosis. However, if miR-476b influences macrophage LPL
      expression and the subsequent effects are unknown. Here, we utilized oxLDL
      treatment RAW 264.7 macrophages that were transfected with miR-467b mimics or
      inhibitors to investigate the potential roles of macrophage miR-476b. We found
      that miR-467b significantly decreased lipid accumulation and IL-6, IL-1beta, TNF
      alpha and MCP-1 secretions. Furthermore, our studies suggested an additional
      explanation for the regulatory mechanism of miR-467b on its functional target,
      LPL in RAW 264.7 macrophages. Thus, our findings indicate that miR-467b may
      regulate lipid accumulation and proinflammatory cytokine secretion in oxLDL
      stimulated RAW 264.7 macrophages by targeting the LPL gene.

PMID- 22963824
TI  - Prognostic value of cathepsin L and its inhibitor headpin in oral squamous cell
      carcinoma.
AB  - OBJECTIVE: To investigate the clinicopathological and prognostic significance of
      the expression of cathepsin L and its inhibitor headpin, in oral squamous cell
      carcinoma. DESIGN: Immunohistochemical studies were performed on 56 oral squamous
      cell carcinoma samples. We evaluated the relationship between cathepsin L and
      headpin expression versus patients' clinicopathological factors and survival.
      RESULTS: The group that was positive for cathepsin L expression tended to have
      positive metastatic neck lymph nodes and a poorer prognosis. Headpin expression
      was not related to metastasis or prognosis. Well differentiated squamous cell
      carcinoma had higher levels of headpin expression compared with poorly
      differentiated squamous cell carcinoma. CONCLUSION: Cathepsin L expression is
      related to the invasive and metastatic potential of oral squamous cell carcinoma.

PMID- 22963825
TI  - Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor
      of MDA-MB-231 breast cancer cell migration.
AB  - Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis
      plant, has been reported to possess diverse biological activities, including anti
      proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic
      decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies
      have investigated whether CBDA itself is biologically active. Results of the
      current investigation revealed that CBDA inhibits migration of the highly
      invasive MDA-MB-231 human breast cancer cells, apparently through a mechanism
      involving inhibition of cAMP-dependent protein kinase A, coupled with an
      activation of the small GTPase, RhoA. It is established that activation of the
      RhoA signaling pathway leads to inhibition of the mobility of various cancer
      cells, including MDA-MB-231 cells. The data presented in this report suggest for
      the first time that as an active component in the cannabis plant, CBDA offers
      potential therapeutic modality in the abrogation of cancer cell migration,
      including aggressive breast cancers.

PMID- 22963826
TI  - A comparison of the movement characteristics between the kneeling gait and the
      normal gait in healthy adults.
AB  - BACKGROUND: Trainings of the kneeling position, such as standing exercise on the
      knees and kneeling gait, have been anecdotally used in physical therapy to
      improve postural control of patients with various pathological conditions.
      However, clinical evidence is lacking and the movement characteristics of these
      kneeling trainings have not been well explored. The purpose of this study is to
      clarify the movement characteristics of the kneeling gait compared with the
      normal gait. METHODS: Twenty healthy volunteers (10 men and 10 women) aged 22-34
      years were recruited. Participants were required to perform the kneeling gait and
      the normal gait at a self-selected comfortable speed on the treadmill. Surface
      electromyograms (EMG) and center of mass (COM) displacements were measured during
      each task. RESULTS: The EMGs of the gait-related proximal muscles during the
      kneeling gait were greater than during the normal gait, even at a comfortable
      speed. The COM displacement to the lateral direction was longer during the
      kneeling gait than it was during the normal gait. Furthermore, mechanical energy
      efficiency during the kneeling gait was less than that during the normal gait.
      CONCLUSION: The results suggest that the kneeling gait is an effective exercise
      to strengthen the gait-related proximal muscles. The increased muscle activities
      during the kneeling gait were probably due to the compensatory movements of the
      trunk and the pelvis.

PMID- 22963827
TI  - Medial knee joint loading during stair ambulation and walking while carrying
      loads.
AB  - Carrying loads while walking or using stairs is a common activity of daily
      living. Knee osteoarthritis is associated with increased external knee adduction
      moment (KAM) during walking, so understanding how the additional challenges of
      stairs and carrying loads impact these moments is of value. Sixteen healthy
      individuals performed three types of MOTION (walking, stair ascent, stair
      descent) under three LOAD conditions (no load, carrying a 13.6kg front load,
      carrying 13.6kg load in a backpack). Three-dimensional gait analysis was used to
      measure KAM. Results of ANOVA showed a significant main effect of both MOTION and
      LOAD on peak KAM (p<0.001), but no significant MOTION*LOAD interaction (p=0.250).
      Peak KAM during stair ascent was about two-times those seen in stair descent
      (p<0.001) and was significantly higher than those seen in walking (p<0.001).
      Conditions with LOAD generated significantly greater KAM as compared to the no
      LOAD conditions (p<0.001). These findings suggest that carrying a load of
      moderate magnitude while climbing stairs significantly increases the peak KAM - a
      risk factor associated with knee osteoarthritis.

PMID- 22963828
TI  - Validation of a thermal bias control technique for Coda Wave Interferometry
      (CWI).
AB  - The Coda Wave Interferometry (CWI) analysis serves to monitor the variation of
      propagation velocity in a heterogeneous medium with high precision (10(-3)% in
      relative terms). In combination with acoustoelastic theory, this type of analysis
      offers an NDT method for stress evaluation and/or damage detection. Since the CWI
      method is intended to evaluate extreme levels of accuracy, the presence of bias
      under certain circumstances can undermine evaluation results and/or test
      repeatability. In this paper, we offer a bias control technique involving the use
      of a second (reference) specimen for CWI analysis that is designed to compensate:
      (1) the thermally-induced velocity variation due to environmental temperature
      fluctuations; and (2) bias originating from experimental procedures. The
      presentation of this technique contains both a theoretical analysis and
      experimental protocol for the purpose of implementation. Furthermore, comparisons
      of experimental results have been included in order to demonstrate the utility of
      this bias control technique under laboratory conditions.

PMID- 22963829
TI  - Ultrasonic field profile evaluation in acoustically inhomogeneous anisotropic
      materials using 2D ray tracing model: Numerical and experimental comparison.
AB  - Ultrasound propagation in inhomogeneous anisotropic materials is difficult to
      examine because of the directional dependency of elastic properties. Simulation
      tools play an important role in developing advanced reliable ultrasonic non
      destructive testing techniques for the inspection of anisotropic materials
      particularly austenitic cladded materials, austenitic welds and dissimilar welds.
      In this contribution we present an adapted 2D ray tracing model for evaluating
      ultrasonic wave fields quantitatively in inhomogeneous anisotropic materials.
      Inhomogeneity in the anisotropic material is represented by discretizing into
      several homogeneous layers. According to ray tracing model, ultrasonic ray paths
      are traced during its energy propagation through various discretized layers of
      the material and at each interface the problem of reflection and transmission is
      solved. The presented algorithm evaluates the transducer excited ultrasonic
      fields accurately by taking into account the directivity of the transducer,
      divergence of the ray bundle, density of rays and phase relations as well as
      transmission coefficients. The ray tracing model is able to calculate the
      ultrasonic wave fields generated by a point source as well as a finite dimension
      transducer. The ray tracing model results are validated quantitatively with the
      results obtained from 2D Elastodynamic Finite Integration Technique (EFIT) on
      several configurations generally occurring in the ultrasonic non destructive
      testing of anisotropic materials. Finally, the quantitative comparison of ray
      tracing model results with experiments on 32mm thick austenitic weld material and
      62mm thick austenitic cladded material is discussed.

PMID- 22963830
TI  - The computations of reflection coefficients of multilayer structure based on the
      reformulation of Thomson-Haskell method.
AB  - A reformulation of the Thomson-Haskell method is presented for calculating the
      reflection coefficients of multilayer structure immersing in the coupling fluid.
      Instead of directly multiplying the layer propagator matrix, the new method
      splits the layer propagator matrix and excursively determines the interface
      stiffness matrix starting from the bottom half-space with known stiffness. A
      formulation for the reflection coefficients is derived based on the obtained
      interface stiffness matrix of the top layer. This scheme can be applied to a
      single solid layers or layered structures containing both fluid and solid layers.
      It keeps the simplicity but naturally excludes the exponential growth term and
      thus can be applied at any frequency range. Its validity and feasibility were
      experimentally proved by the measurement of the reflection coefficients of a
      three layered structure of aluminum-glass-aluminum and a sandwiched layer
      structure of two 250 MUm stainless plates filled with 100 MUm deionized water
      based on the inversion of V(z, t) technique. The result of experiments is
      consistent with the theoretical calculation. The reformulation of the Thomson
      Haskell method offers an efficient and effective solution for calculating the
      acoustic reflection coefficients of multilayer structures of any configurations.

PMID- 22963831
TI  - The choreography of the intermittent electrocardiographic Brugada pattern from
      beat to beat.

PMID- 22963832
TI  - Allograft vasculopathy vs. coronary artery disease: comparison by optical
      coherence tomography.

PMID- 22963833
TI  - Effect of antihypertensive therapy on ventricular-arterial mechanics, coupling,
      and efficiency.
AB  - AIMS: To investigate the effect of antihypertensive therapy on ventricular
      arterial mechanics, coupling, and efficiency in early-stage hypertension. METHODS
      AND RESULTS: We studied 527 participants from two clinical trials assessing the
      effect of blood pressure lowering on diastolic function. Participants were aged
      >=45 years with early-stage hypertension, no heart failure, ejection fraction
      (EF) >=50%, and diastolic dysfunction using Doppler echocardiography. Effective
      arterial afterload and its components were assessed along with measures of left
      ventricular (LV) structure and function prior to and after 24-38 weeks of
      antihypertensive therapy. Systolic blood pressure decreased from 154 +/- 18 to
      137 +/- 15 mmHg at follow-up. Blood pressure reduction was associated with
      decreases in ventricular and arterial stiffness, improvements in systemic
      arterial compliance and resistance, enhanced LV ejection, and reduction in
      cardiac work (all P < 0.001). Changes in Ea/Ees ratio were inversely correlated
      with those in EF (r = -0.25; P < 0.001), stroke work index (r = -0.13; P =
      0.007), and LV efficiency (r = -0.98; P < 0.001); and directly related to changes
      in mitral E/e' (r = 0.12; P = 0.01). Adjusting for age and blood pressure change,
      women and obese individuals had less enhancement in ventricular-arterial coupling
      and efficiency compared with men and non-obese individuals (P = 0.04 and 0.007,
      respectively). CONCLUSION: Antihypertensive therapy reduces arterial and
      ventricular stiffness, enhances ventricular-arterial coupling, reduces cardiac
      work, and improves LV efficiency, systolic, and diastolic function. Attenuated
      responses in women and among obese subjects suggest that structure-function
      changes may be less reversible in these groups, possibly explaining their greater
      susceptibility to ultimately develop heart failure.

PMID- 22963834
TI  - Optical sensing for tumor detection in the liver.
AB  - BACKGROUND: There is an increasing trend for optical guidance techniques in
      surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can
      distinguish different tissue types through a specific "optical fingerprint". We
      investigated whether DRS could discriminate metastatic tumor tissue from normal
      liver tissue and thus if this technique would have potential for further
      implementation into surgical instruments or radiological intervention tools.
      METHODS: A miniaturized optical needle was developed able to collect DRS spectra
      between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal
      liver metastases were analyzed with DRS immediately after resection. Multiple
      measurements were performed and DRS results were compared to the histology
      analysis of the measurement locations. In addition, normal liver tissue was
      scored for the presence or absence of steatosis. RESULTS: A total of 780 out of
      the 828 optical measurements were correctly classified into either normal or
      tumor tissue. The resulting sensitivity and specificity were both 94%. The
      results of the analysis for each patient individually showed an accuracy of 100%.
      The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis
      in liver tissue compared to that of the pathologist was 0.86. CONCLUSIONS: DRS
      demonstrates a high accuracy in discriminating normal liver tissue from
      colorectal liver metastases. DRS can also predict the degree of hepatic steatosis
      with high accuracy. The technique, here demonstrated in a needle like probe, may
      as such be incorporated into surgical tools for optical guided surgery or
      percutaneous needles for radiological interventions.

PMID- 22963835
TI  - Neural correlates of object-based attentional selection in human cortex.
AB  - Humans can attend to different objects independent of their spatial locations.
      While selecting an object has been shown to modulate object processing in high
      level visual areas in occipitotemporal cortex, where/how behavioral importance
      (i.e., priority) for objects is represented is unknown. Here we examined the
      patterns of distributed neural activity during an object-based selection task. We
      measured brain activity with functional magnetic resonance imaging (fMRI), while
      participants viewed two superimposed, dynamic objects (left- and right-pointing
      triangles) and were cued to attend to one of the triangle objects. Enhanced fMRI
      response was observed for the attention conditions compared to a neutral
      condition, but no significant difference was found in overall response amplitude
      between two attention conditions. By using multi-voxel pattern classification
      (MVPC), however, we were able to distinguish the neural patterns associated with
      attention to different objects in early visual cortex (V1 to hMT+) and lateral
      occipital complex (LOC). Furthermore, distinct multi-voxel patterns were also
      observed in frontal and parietal areas. Our results demonstrate that object-based
      attention has a wide-spread modulation effect along the visual hierarchy and
      suggest that object-specific priority information is represented by patterned
      neural activity in the dorsal frontoparietal network.

PMID- 22963837
TI  - Effects of choline on sodium arsenite-induced neural tube defects in chick
      embryos.
AB  - Arsenic passes through the placenta and accumulates in the neuroepithelium of
      embryo, whereby inducing congenital malformations such as neural tube defects
      (NTDs) in animals. Choline (CHO), a methyl-rich nutrient, functions as a methyl
      donor to participate in methyl group metabolism. Arsenic methylation has been
      regarded as a detoxification process and choline (CHO) is the major source of
      methyl-groups. However, whether CHO intake reverses the abnormal embryo
      development induced by sodium arsenite (SA) and the relationship between CHO
      intake and arsenite-induced NTDs are still unclear. In this study, we used chick
      embryos as animal model to investigate the effects of SA and CHO supplementation
      on the early development of nervous system. Our results showed that the
      administration of SA led to reduction in embryo viability, embryo body weight and
      extraembryonic vascular area, accompanied by a significantly increased incidence
      of the failed closure of the caudal end of the neural tube. CHO, at low dose (25
      MUg/MUL), reversed the decrease in embryo viability and the increase in the
      failed closure of the caudal end of the neural tube, which were induced by SA. In
      addition, CHO (25 MUg/MUL) inhibited not only the SA-induced cell apoptosis by up
      regulating Bcl-2 level, but also the global DNA methylation by increasing the
      expressions of DNMT1 and DNMT3a. However, less significant difference was found
      between the embryos co-treated with SA and CHO (50 MUg/MUL) and the ones treated
      with SA alone. Taken together, these findings suggest that low dose CHO could
      protect chick embryos from arsenite-induced NTDs by a possible mechanism related
      to the methyl metabolism.

PMID- 22963836
TI  - Timing and route of exposure affects crystal formation in melamine and cyanuric
      exposed male and female rats: gavage vs. feeding.
AB  - Effects of the dosing matrix and timing on the onset of renal crystal formation
      were evaluated in male and non-pregnant female rats (Fisher 344) exposed to both
      melamine (MEL) and cyanuric acid (CYA) for 28 days. Rats were fed ground feed
      containing 60 ppm MEL and 60 ppm CYA, (5 mg/kg bw/day equivalent), or exposed via
      oral gavage to carboxymethylcellulose containing 5 mg/kg bw MEL followed by 5
      mg/kg bw CYA either consecutively (<1 min apart) or delayed 45 min after MEL.
      Staggered gavage exposure to MEL/CYA caused extensive renal crystal formation as
      compared to when the two compounds were administered consecutively or in feed.
      Treatment related effects included reduced weight gain, feed consumption, and
      testicular weight and increased kidney weight, water consumption and urine
      output. Animals from the staggered MEL/CYA gavage exposure group became ill and
      were removed after 9 days of exposure. Approximately 1 week after the initiation
      of exposure microscopic urinalysis revealed MEL/CYA crystals in both groups of
      gavaged animals but not in the MEL/CYA feed treatment groups. Urinary crystals
      were smaller (10 MUm) in animals consecutively gavaged. In contrast the urinary
      crystals were larger (20-40 MUm) and frequently clumped in the animals in the
      staggered gavage group.

PMID- 22963838
TI  - In vitro and in vivo antimicrobial activity of Algerian Hoggar Salvadora persica
      L. extracts against microbial strains from children's oral cavity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvadora persica L. (miswak) is traditionally
      used to ensure oral hygiene Muslim people in developing countries where it is
      growing. The antibacterial properties of Salvadora persica L. originating from
      various geographic areas have already been reported. However, they have never
      been tested for samples originating from Hoggar, where extreme weather conditions
      could lead to different properties for this Salvadora persica L. ecotype. AIM OF
      THE STUDY: To assess the in vitro and in vivo antimicrobial activities of
      methanolic extract of Algerian Hoggar Salvadora persica L. (miswak) on some
      isolated and identified strains from the oral cavity of school children aged from
      6 to 12 with (n=20) and without (n=20) caries. MATERIALS AND METHODS: After a
      qualitative and quantitative analysis of dental plaque samples from the selected
      children, the effect of methanolic extract of Hoggar miswak against oral
      bacterial and fungal strains isolated from the oral cavity of children with
      caries was tested by both agar disc diffusion and microdilution methods. The
      stability and physicochemical parameters of Hoggar Salvadora persica L. mouthwash
      were also assessed compared. The in vivo antimicrobial effect of Hoggar miswak
      rinse on dental plaque samples was also tested over a week. RESULTS: Four
      bacterial genera (Staphylococcus, Streptococcus, Escherichia and Lactobacillus)
      were commonly identified in all subjects at different colonization levels. A
      statistically significant difference in colonization levels between the two
      groups of children was recorded. Hoggar miswak extract more significantly
      inhibited the growth of Gram negative bacteria from the dental plaque than Gram
      positive ones. Hoggar Salvadora persica L. mouthwash was stable at 4  degrees C
      and 25  degrees C over the period of conservation (one week) while a temperature
      of 40  degrees C induced variations in the physicochemical parameters and
      considered not suitable for preservation. The in vivo study revealed a
      significant reduction in bacteria of the oral cavity using miswak mouthwash as
      compared to placebo. CONCLUSION: Hoggar miswak extract displayed a strong
      antimicrobial effect both in vitro and in vivo. Its use as a mouthrinse could
      therefore be recommended as a preventive measure to preserve from tooth decay.

PMID- 22963839
TI  - Nodal marginal zone B cell lymphoma with prominent follicular colonization with
      deletion of chromosome 13.
AB  - Nodal marginal zone B cell lymphoma is a rare type of malignant lymphoma and
      appears to be heterogeneous. Here we report a 60-year-old woman with stage I
      splenic type of nodal marginal zone B cell lymphoma with prominent follicular
      colonization. She was treated only by radiation therapy, and remained free of
      disease on examination for 4 years. The lymph node cells showed an abnormal
      chromosome of deletion 13, although neither bone marrow cells nor peripheral
      blood cells demonstrated the same abnormal chromosome. This type of chromosomal
      abnormality has not been previously reported and may be related to good prognosis
      in the present case.

PMID- 22963840
TI  - Mast cell sarcoma of the scalp: the first sign of undisclosed systemic
      mastocytosis?
AB  - Mastocytosis is a neoplastic disease of mast cells and their CD34+ precursors,
      including a heterogeneous group of disorders. It is characterized by abnormal
      growth and accumulation of mast cells in one or more organ systems. Mast cell
      sarcoma is an extremely rare and aggressive disease characterized by local
      proliferation of atypical mast cells, destructive growth and poor prognosis,
      without systemic involvement. Very few clinical cases describing this entity have
      been reported in the literature. In this paper, we report a case of a mast cell
      sarcoma, localized in the scalp of a 63-year-old woman; it appears to be the
      first manifestation of undisclosed systemic mastocytosis.

PMID- 22963841
TI  - Posttransplant cellular immune reactivity against donor antigen correlates with
      clinical islet transplantation outcome: towards a better posttransplant
      monitoring.
AB  - The aim of the present study was to assess the efficiency of cell-based immune
      assays in the detection of alloreactivity after islet transplantation and to
      correlate these results with clinical outcome. Mixed lymphocyte cultures were
      performed with peripheral blood mononuclear cells from recipients (n = 14),
      donors, or third party. The immune reactivity was assessed by the release of IFN
      gamma (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine
      quantification (Bioplex). Islet function correlated with the number of IFN-gamma
      secreting cells following incubation with donor cells (p = 0.007, r = -0.50), but
      not with third party cells (p = 0.61). Similarly, a high number of donor-specific
      proliferating cells was associated with a low islet function (p = 0.006, r = 
      0.51). Proliferating cells were mainly CD3(+)CD4(+) lymphocytes and CD3(-)CD56(+)
      natural killer cells (with low levels of CD3(+)CD8(+) lymphocytes). Patients with
      low islet function had increased levels of CD4(+)Ki67(+)cells (p <= 0.0001),
      while no difference was observed in CD8(+)Ki67(+) and CD56(+)Ki67(+) cells. IFN
      gamma, IL-5, and IL-17 levels were increased in patients with low islet function,
      but IL-10 levels tended to be lower. IFN-gamma-ELISpot, proliferation, and
      cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 +/-
      0.088, 0.85 +/- 0.084, and 0.88 +/- 0.074, respectively). Cellular immune
      reactivity against donor cells correlates with posttransplant islet function. The
      tested assays have the potential to be of substantial help in the management of
      islet graft recipients and deserve prospective validation.

PMID- 22963842
TI  - The relationship between vestibular aqueduct diameter and sensorineural hearing
      loss is linear: a review and meta-analysis of large case series.
AB  - INTRODUCTION: Inner ear homeostasis is dependent on the vestibular aqueduct and
      its content, the endolymphatic duct. Narrow and enlarged vestibular aqueducts
      have both been associated with hearing loss in Meniere's and large vestibular
      aqueduct syndromes. This review investigated the correlation between vestibular
      aqueduct diameter and pure tone average, and the effect of measurement site (i.e.
      the midpoint or the external aperture). MATERIALS AND METHODS: A systematic
      review of the literature and meta-analysis of large case series published on the
      Allied and Complementary Medicine, British Nursing Index, Cumulative Index to
      Nursing and Allied Health, Embase, Health Business Elite, Health Management
      Information Consortium, Medline, PsycInfo and PubMed databases. References and
      personal books were also scrutinised. RESULTS: A linear relationship between
      vestibular aqueduct diameter and hearing loss was observed, with a projected
      increase of 6 dBHL per unit of vestibular aqueduct diameter (95 per cent
      confidence interval, 2-10; p = 0.003). This relationship was independent of
      measurement site. DISCUSSION: This dose-dependent or linear relationship supports
      the role of flow and/or pressure change as aetiological factors in the
      pathogenesis of hearing loss, as per Poiseuille's law. This aetiological
      association is strengthened by the fact that the observed relationship is
      independent of measurement site.

PMID- 22963843
TI  - Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in
      blood and of DEHP metabolites in urine of male volunteers after single ingestion
      of ring-deuterated DEHP.
AB  - The plasticizer di(2-ethylhexyl) phthalate (DEHP) is suspected to induce
      antiandrogenic effects in men via its metabolite mono(2-ethylhexyl) phthalate
      (MEHP). However, there is only little information on the kinetic behavior of DEHP
      and its metabolites in humans. The toxikokinetics of DEHP was investigated in
      four male volunteers (28-61y) who ingested a single dose (645+/-20MUg/kg body
      weight) of ring-deuterated DEHP (DEHP-D(4)). Concentrations of DEHP-D(4), of free
      ring-deuterated MEHP (MEHP-D(4)), and the sum of free and glucuronidated MEHP
      D(4) were measured in blood for up to 24h; amounts of the monoesters MEHP-D(4),
      ring-deuterated mono(2-ethyl-5-hydroxyhexyl) phthalate and ring-deuterated mono(2
      ethyl-5-oxohexyl) phthalate were determined in urine for up to 46h after
      ingestion. The bioavailability of DEHP-D(4) was surprisingly high with an area
      under the concentration-time curve until 24h (AUC) amounting to 50% of that of
      free MEHP-D(4). The AUC of free MEHP-D(4) normalized to DEHP-D(4) dose and body
      weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D(4) even 50 and 100 times
      higher than the corresponding AUC/D values obtained earlier in rat and marmoset,
      respectively. Time courses of the compounds in blood and urine of the volunteers
      oscillated widely. Terminal elimination half-lives were short (4.3-6.6h). Total
      amounts of metabolites in 22-h urine are correlated linearly with the AUC of free
      MEHP-D(4) in blood, the parameter regarded as relevant for risk assessment.

PMID- 22963844
TI  - Should I stay or should I go? A study exploring why healthcare students consider
      leaving their programme.
AB  - BACKGROUND: Attrition in healthcare programmes is a growing concern
      internationally. Students leave for a variety of reasons but it is difficult to
      understand the complex interactions that eventually lead to attrition.
      OBJECTIVES: The objectives of this study were to identify the factors that
      prompted students to consider leaving their programme, and to make
      recommendations regarding strategies to reduce attrition. DESIGN: One aspect of a
      larger survey, which itself was part of a larger sequential mixed methods study.
      SETTINGS: Nine universities in the North West of England. METHODS: An online
      survey developed as part of a mixed methods sequential exploratory study was
      completed by students on nursing and allied-health programmes. The detailed
      responses obtained for a question relating to if the students have ever
      considered leaving their current programme were analysed both quantitatively
      (content analysis) and qualitatively (framework analysis). RESULTS: 1080 students
      completed the survey (an estimated 11% response rate); of this group 999 students
      answered the question 'have you ever considered leaving your current programme?'
      465 students (47%) indicated that they had considered leaving and provided
      detailed comments explaining the circumstances that induced them to deliberate
      whether or not to stay. A thematic analysis of the data found three distinct
      themes: dissatisfaction with academic workload and support; difficulties
      associated with clinical placements, and personal concerns and challenges. A
      significant number of student comments combined two or more of these themes. A
      number of students also detailed why they decided to stay. CONCLUSIONS: Those
      students that had considered leaving frequently described how a combination of
      diverse factors accumulated to lead to them contemplating leaving their
      programme. Strategies to reduce attrition in healthcare students need to consider
      the student lifecycle from recruitment to graduation, to set reasonable student
      expectations and ensure that a career within healthcare is both desired and
      valued.

PMID- 22963845
TI  - Cytotoxic aspects of gadolinium oxide nanostructures for up-conversion and NIR
      bioimaging.
AB  - Bioimaging is an important diagnostic tool in the investigation and visualization
      of biological phenomena in cells and in medicine. In this context, up-converting
      Gd(2)O(3):Er(3+),Yb(3+) nanostructures (nanoparticles, nanorods) have been
      synthesized by precipitation methods and hydrothermal synthesis. Independent of
      size and morphology, Gd(2)O(3):Er(3+),Yb(3+) powders show up-conversion (550 nm,
      670 nm) and near-infrared emission (1.5 MUm) upon 980 nm excitation, which makes
      these structures interesting for application as biomarkers. With regard to their
      potential application in bioimaging, cytotoxicity is an important aspect and is
      strongly affected by the physico-chemical properties of the investigated
      nanostructures. Therefore, the cytotoxic effect of bare and poly(ethylene glycol)
      b-poly(acrylic acid) block co-polymer-modified nanostructures on non-phagocytic
      and phagocytic cells (B-cell hybridoma cells and macrophages) was investigated.
      The observed cytotoxic behavior in the case of macrophages incubated with bare
      nanostructures was assigned to the poor chemical durability of gadolinium oxide,
      but could be overcome by surface modification.

PMID- 22963846
TI  - Effect of a plasmaelectrolytic coating on the strength retention of in vivo and
      in vitro degraded magnesium implants.
AB  - The strength decrease in magnesium implants was studied in vitro and in vivo,
      with and without a protective plasmaelectrolytic coating. In vivo, degradation
      was examined by implanting rectangular plates on top of the nasal bone of
      miniature pigs. The presence of gas pockets in the soft tissue surrounding the
      implants was evaluated with intermediate X-rays and computed X-ray tomography
      scans before euthanasia. After 12 and 24 weeks of in vivo degradation, the large
      rectangular plates were removed and mechanically tested in three-point bending.
      In vitro, identical plates were immersed in simulated body fluid for 4, 8 and 12
      weeks. In vitro and in vivo results showed that onset of gas release can be
      delayed by the plasmaelectrolytic coating. Mass loss and strength retention
      during in vivo degradation is about four times slower than during in vitro
      degradation for the chosen test conditions. Despite the slow degradation of the
      investigated WE43 alloy, the occurrence of gas pockets could not be completely
      avoided. Nevertheless, uniformity of degradation and reliable strength retention
      make this alloy a prime candidate for the use of magnesium in cranio
      maxillofacial surgery.

PMID- 22963847
TI  - Resorbable composites with bioresorbable glass fibers for load-bearing
      applications. In vitro degradation and degradation mechanism.
AB  - An in vitro degradation study of three bioresorbable glass fiber-reinforced
      poly(l-lactide-co-dl-lactide) (PLDLA) composites was carried out in simulated
      body fluid (SBF), to simulate body conditions, and deionized water, to evaluate
      the nature of the degradation products. The changes in mechanical and chemical
      properties were systematically characterized over 52 weeks dissolution time to
      determine the degradation mechanism and investigate strength retention by the
      bioresorbable glass fiber-reinforced PLDLA composite. The degradation mechanism
      was found to be a combination of surface and bulk erosion and does not follow the
      typical core-accelerated degradation mechanism of poly(alpha-hydroxyacids).
      Strength retention by bioresorbable glass fiber-reinforced PLDLA composites can
      be tailored by changing the oxide composition of the glass fibers, but the
      structure-property relationship of the glass fibers has to be understood and
      controlled so that the phenomenon of ion leaching can be utilized to control the
      degradation rate. Therefore, these high performance composites are likely to open
      up several new possibilities for utilizing resorbable materials in clinical
      applications which could not be realized in the past.

PMID- 22963848
TI  - Time-dependent mechanical properties of aortic valve cusps: effect of
      glycosaminoglycan depletion.
AB  - Aortic valve (AV) performance is closely linked to its structural components.
      Glycosaminoglycans (GAGs) are thought to influence the time-dependent properties
      of living tissues. This study investigates the effect of GAGs on the viscoelastic
      behaviour of the AV. Fresh porcine AV cusps were either treated enzymatically to
      remove GAGs or left untreated (control). The specimens were tested for stress
      relaxation and tensile properties under equibiaxial load conditions. The stress
      relaxation curves were fitted using a double exponential decay equation and the
      early relaxation constant (tau(1)) and late relaxation constant (tau(2))
      calculated for each specimen. Immunohistochemistry confirmed the successful
      depletion of both sulphated and non-sulphated GAGs from the AV cusps. A
      statistical increase in tau(1) was found for both the radial and circumferential
      directions between the control and -GAGs group (radial, control 17.37s vs. -GAGs
      25.65 s; circumferential, control 21.47s vs. -GAGs 27.37 s). It was also found
      that tau(1) differed between the two directions for the control group but not
      after GAG depletion (control, radial 17.37s vs. circumferential 21.47 s; -GAGs,
      radial 25.65 s vs. circumferential 27.37s). No effect on stiffness was found. The
      results showed that the presence of GAGs influences the mechanical viscoelastic
      properties of the AV but has no effect on the stiffness. The natural anisotropy,
      which reflects the relaxation kinematics, is lost after GAG depletion.

PMID- 22963849
TI  - Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle
      myogenesis.
AB  - Cellulose nanowhiskers (CNWs) are high-aspect-ratio rod-like nanoparticles
      prepared via partial hydrolysis of cellulose. For the first time, CNWs have been
      extracted from the marine invertebrate Ascidiella aspersa, yielding animal
      derived CNWs with particularly small diameters of only a few nanometres. Oriented
      surfaces of adsorbed CNWs were prepared using a flexible and facile spin-coating
      method, allowing the modulation of CNW adsorption and relative orientation. Due
      to the shape and nanoscale dimensions of the CNWs, C2C12 myoblasts adopted
      increasingly oriented morphologies in response to more densely adsorbed and
      oriented CNW surfaces. In addition, the degree of myoblast fusion was greatest on
      the highly oriented CNW surfaces, and even low-orientation CNW surfaces promoted
      more extensive fusion than flat control surfaces. Highly oriented multinuclear
      myotubes formed on the oriented CNW surfaces and fibrillar fibronectin deposited
      on the surfaces was also modelled in a highly oriented arrangement after only 4
      days in culture. With a mean feature height of only 5-6 nm, the CNW surfaces
      present the smallest features ever reported to induce contact guidance in
      skeletal muscle myoblasts, highlighting the potential for nanoscale materials for
      engineering oriented tissues such as skeletal muscle.

PMID- 22963850
TI  - Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs.
AB  - The use of hybrid pH-sensitive micelles based mainly on the
      (PEO)(129)(P2VP)(43)(PCL)(17) ABC miktoarm star copolymer as potential triggered
      drug delivery systems was investigated. Co-micellization of this star copolymer
      with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH
      sensitive block (poly-2-vinylpyridine) is considered here in order to impart
      possible active targeting of the tumor cells. Two architectures were studied for
      these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer, and
      the respective hybrid micelles are compared in terms of cytotoxicity (cells
      viability) and cellular uptake (using fluorescent dye loaded micelles). Finally,
      the triggered drug release in the cytosol of tumor cells was investigated by
      studying, on the one hand, the lysosomal integrity after internalization and, on
      the other hand, the release profile in function of the pH.

PMID- 22963851
TI  - Self-assembled octapeptide scaffolds for in vitro chondrocyte culture.
AB  - Nature has evolved a variety of creative approaches to many aspects of materials
      synthesis and microstructural control. Molecular self-assembly is a simple and
      efficient way to fabricate complex nanostructures such as hydrogels. We have
      recently investigated the gelation properties of a series of ionic-complementary
      peptides based on the alternation of non-polar hydrophobic and polar hydrophilic
      residues. In this work we focus on one specific octapeptide, FEFEFKFK (F,
      phenylalanine; E, glutamic acid; K, lysine). This peptide was shown to self
      assemble in solution and form beta-sheet-rich nanofibres which, above a critical
      gelation concentration, entangle to form a self-supporting hydrogel. The fibre
      morphology of the hydrogel was analysed using transmission electron microscopy
      and cryo-scanning electron microscopy illustrating a dense fibrillar network of
      nanometer size fibres. Oscillatory rheology results show that the hydrogel
      possesses visco-elastic properties. Bovine chondrocytes were used to assess the
      biocompatibility of the scaffolds over 21 days under two-dimensional (2-D) and
      three-dimensional (3-D) cell culture conditions, particularly looking at cell
      morphology, proliferation and matrix deposition. 2-D culture resulted in cell
      viability and collagen type I deposition. In 3-D culture the mechanically stable
      gel was shown to support the viability of cells, the retention of cell morphology
      and collagen type II deposition. Subsequently the scaffold may serve as a
      template for cartilage tissue engineering.

PMID- 22963852
TI  - The temporal derivative of expected utility: a neural mechanism for dynamic
      decision-making.
AB  - Real world tasks involving moving targets, such as driving a vehicle, are
      performed based on continuous decisions thought to depend upon the temporal
      derivative of the expected utility (?V/?t), where the expected utility (V) is the
      effective value of a future reward. However, the neural mechanisms that underlie
      dynamic decision-making are not well understood. This study investigates human
      neural correlates of both V and ?V/?t using fMRI and a novel experimental
      paradigm based on a pursuit-evasion game optimized to isolate components of
      dynamic decision processes. Our behavioral data show that players of the pursuit
      evasion game adopt an exponential discounting function, supporting the expected
      utility theory. The continuous functions of V and ?V/?t were derived from the
      behavioral data and applied as regressors in fMRI analysis, enabling temporal
      resolution that exceeded the sampling rate of image acquisition, hyper-temporal
      resolution, by taking advantage of numerous trials that provide rich and
      independent manipulation of those variables. V and ?V/?t were each associated
      with distinct neural activity. Specifically, ?V/?t was associated with anterior
      and posterior cingulate cortices, superior parietal lobule, and ventral pallidum,
      whereas V was primarily associated with supplementary motor, pre and post central
      gyri, cerebellum, and thalamus. The association between the ?V/?t and brain
      regions previously related to decision-making is consistent with the primary role
      of the temporal derivative of expected utility in dynamic decision-making.

PMID- 22963853
TI  - Bessel Fourier Orientation Reconstruction (BFOR): an analytical diffusion
      propagator reconstruction for hybrid diffusion imaging and computation of q-space
      indices.
AB  - The ensemble average propagator (EAP) describes the 3D average diffusion process
      of water molecules, capturing both its radial and angular contents. The EAP can
      thus provide richer information about complex tissue microstructure properties
      than the orientation distribution function (ODF), an angular feature of the EAP.
      Recently, several analytical EAP reconstruction schemes for multiple q-shell
      acquisitions have been proposed, such as diffusion propagator imaging (DPI) and
      spherical polar Fourier imaging (SPFI). In this study, a new analytical EAP
      reconstruction method is proposed, called Bessel Fourier Orientation
      Reconstruction (BFOR), whose solution is based on heat equation estimation of the
      diffusion signal for each shell acquisition, and is validated on both synthetic
      and real datasets. A significant portion of the paper is dedicated to comparing
      BFOR, SPFI, and DPI using hybrid, non-Cartesian sampling for multiple b-value
      acquisitions. Ways to mitigate the effects of Gibbs ringing on EAP reconstruction
      are also explored. In addition to analytical EAP reconstruction, the
      aforementioned modeling bases can be used to obtain rotationally invariant q
      space indices of potential clinical value, an avenue which has not yet been
      thoroughly explored. Three such measures are computed: zero-displacement
      probability (Po), mean squared displacement (MSD), and generalized fractional
      anisotropy (GFA).

PMID- 22963854
TI  - BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly -
      evidence from auditory distraction.
AB  - Aging affects the ability to focus attention on a given task and to ignore
      distractors. These functions subserve response control processes for which fronto
      striatal networks have been shown to play an important role. Within these
      networks, the brain-derived-neurotrophic-factor (BDNF), which is known to
      underlie aging effects, plays a pivotal role. We investigated how cognitive
      subprocesses constituting a cycle of distraction, orientation and refocusing of
      attention are affected by the functional BDNF Val66Met polymorphism using event
      related potentials (ERPs) in 122 healthy elderly. Using an auditory distraction
      paradigm we found that the Val/Val genotype confers a disadvantage to its
      carriers. This disadvantage was partly compensated by intensified attentional
      shifting mechanisms. It could be based on response selection processes being more
      vulnerable against interference from distractors in this genotype group.
      Processes reflecting transient sensory memory processes, or the re-orientation of
      attention were not affected by the BDNF Val66Met polymorphism, suggesting a
      higher importance of BDNF for mechanisms related to response control, than
      stimulus processing. The results add on recent literature showing that the Met
      allele confers some benefit to its carriers. We suggest an account for unifying
      different results of BDNF Val66Met association studies in executive functions,
      based on the role of BDNF in fronto-striatal circuits.

PMID- 22963855
TI  - Luminance contrast of a visual stimulus modulates the BOLD response more than the
      cerebral blood flow response in the human brain.
AB  - The blood oxygenation level dependent (BOLD) response measured with functional
      magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood
      flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes
      in neural activity. This response is strongly modulated by the CBF/CMRO(2)
      coupling relationship with activation, defined as n, the ratio of the fractional
      changes. The reliability of the BOLD signal as a quantitative reflection of
      underlying physiological changes depends on the stability of n in response to
      different stimuli. The effect of visual stimulus contrast on this coupling ratio
      was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a
      flickering checkerboard at four visual contrast levels. The theory of the BOLD
      effect makes a robust prediction-independent of details of the model-that if the
      CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between
      the lowest and highest contrast levels should be higher for the BOLD response
      than the CBF response because of the ceiling effect on the BOLD response.
      Instead, this response ratio was significantly lower for the BOLD response (BOLD
      response: 0.23 +/- 0.13, mean +/- SD; CBF response: 0.42 +/- 0.18; p=0.0054).
      This data is consistent with a reduced dynamic range (strongest/weakest response
      ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response
      (~2.4-fold) as luminance contrast increases, corresponding to an increase of n
      from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The
      implication of these results for fMRI studies is that the magnitude of the BOLD
      response does not accurately reflect the magnitude of underlying physiological
      processes.

PMID- 22963856
TI  - Distinct neural correlates of attending speed vs. coherence of motion.
AB  - Attention to specific features of moving visual stimuli modulates the activity in
      human cortical motion sensitive areas. In this study we employed combined event
      related electrophysiological, magnetencephalographic (EEG, MEG) and hemodynamic
      functional magnetic resonance imaging (fMRI) measures of brain activity to
      investigate the precise time course and the neural correlates of feature-based
      attention to speed and coherence. Subjects were presented with an aperture of
      dots randomly moving either slow or fast, at the same time displaying a high or
      low level of coherence. The task was to attend either the speed or the coherence
      and press a button upon the high speed or high coherence stimulus respectively.
      When attention was directed to the speed of motion enhanced neural activity was
      found in the dorsal visual area V3a and in the IPL, areas previously shown to be
      specialized for motion processing. In contrast, when attention was directed to
      the coherence of motion significant hemodynamic activity was observed in the
      parietal areas fIPS and SPL that are specialized for the processing of complex
      motion patterns. Concurrent recordings of the event-related electro- and
      magnetencephalographic responses revealed that the speed-related attentional
      modulations of activity occurred at an earlier time range (around 240-290 ms),
      while the coherence-related ones occurred later (around 320-370 ms) post
      stimulus. The current results suggest that the attentional selection of motion
      features modulates neural processing in the lowest-tier regions required to
      perform the task-critical discrimination.

PMID- 22963858
TI  - Exposure-dose-response of Anadara trapezia to metal contaminated estuarine
      sediments: 3. Selenium spiked sediments.
AB  - Selenium enters near shore marine environments from the activities of coal-fired
      power stations. Although selenium is an essential element, at elevated
      concentrations it can cause genotoxic damage. The relationship between selenium
      exposure dose and response was investigated in Anadara trapezia exposed to
      selenium spiked sediment (5 MUg/g and 20 MUg/g dry mass) for 56 days. A. trapezia
      reached an equilibrium selenium tissue concentration (2 MUg/g and 10 MUg/g
      respectively) by day 42. Gills had significantly more selenium than the
      hepatopancreas and haemolymph. Between 12 and 21% of accumulated selenium in the
      gill and hepatopancreas was detoxified and in the metal rich granule. Most of the
      biologically active selenium in both tissues was in the mitochondrial fraction.
      Glutathione peroxidase activity and mean total glutathione concentrations for
      selenium exposed organisms were not significantly different to controls. The
      ratio of reduced to oxidised glutathione and the total antioxidant capacity were
      significantly reduced in selenium exposed organisms compared to control
      organisms. Increased selenium exposure resulted in significant increases in lipid
      peroxidation, lysosomal destabilisation and an increased frequency of
      micronuclei. A significant exposure-dose-response relationship for A. trapezia
      exposed to selenium enriched sediments indicates that elevated sediment selenium
      concentrations can increased biologically active selenium burdens and cause
      impairment of cellular processes and cell integrity.

PMID- 22963859
TI  - Uranium bioaccumulation in a freshwater ecosystem: impact of feeding ecology.
AB  - The objectives of our study were: (1) to determine if there was significant
      uranium (U) bioaccumulation in a lake that had been historically affected by a U
      mine and (2) to use a combined approach of gut content examination and stable
      nitrogen and carbon isotope analysis to determine if U bioaccumulation in fish
      was linked to foodweb ecology. We collected three species of fish: smallmouth
      bass (Micropterus dolomieu), yellow perch (Perca flavescens) and bluegill
      (Lepomis macrochirus), in addition to several invertebrate species including
      freshwater bivalves (family: Sphaeriidae), dragonfly nymphs (order: Odonata),
      snails (class: Gastropoda) and zooplankton (family: Daphniidae). Results showed
      significant U bioaccumulation in the lake impacted by historical mining
      activities. Uranium accumulation was 2-3 orders of magnitude higher in
      invertebrates than in the fish species. Within fish, U was measured in operculum
      (bone), liver and muscle tissue and accumulation followed the order:
      operculum>liver>muscle. There was a negative relationship between stable nitrogen
      ratios ((15)N/(14)N) and U bioaccumulation, suggesting U biodilution in the
      foodweb. Uranium bioaccumulation in all three tissues (bone, liver, muscle)
      varied among fish species in a consistent manner and followed the order:
      bluegill>yellow perch>smallmouth bass. Collectively, gut content and stable
      isotope analysis suggests that invertebrate-consuming fish species (i.e.
      bluegill) have the highest U levels, while fish species that were mainly
      piscivores (i.e. smallmouth bass) have the lowest U levels. Our study highlights
      the importance of understanding the feeding ecology of fish when trying to
      predict U accumulation.

PMID- 22963857
TI  - A cultured affair: HSV latency and reactivation in neurons.
AB  - After replicating in surface epithelia, herpes simplex virus type-1 (HSV-1)
      enters the axonal terminals of peripheral neurons. The viral genome translocates
      to the nucleus, where it establishes a specialized infection known as latency, re
      emerging periodically to seed new infections. Studies using cultured neuron
      models that faithfully recapitulate the molecular hallmarks of latency and
      reactivation defined in live animal models have provided fresh insight into the
      control of latency and connections to neuronal physiology. With this comes a
      growing appreciation for how the life cycles of HSV-1 and other herpesviruses are
      governed by key host pathways controlling metabolic homeostasis and cell
      identity.

PMID- 22963860
TI  - [Metabolic syndrome: what is it and how useful is the diagnosis in clinical
      practice?].

PMID- 22963861
TI  - [Renal sympathetic denervation for treatment of resistant hypertension].
AB  - Hypertension is an important cardiovascular risk factor and although there have
      been many improvements in pharmacological treatment, a significant percentage of
      patients are still considered resistant. The authors describe two cases of
      radiofrequency renal sympathetic denervation that illustrate the feasibility of
      this new technique for the treatment of resistant hypertension. The procedure
      consists of the application of radiofrequency energy inside the renal arteries to
      ablate afferent and efferent sympathetic renal activity, which has been
      implicated in the pathophysiology of hypertension.

PMID- 22963862
TI  - Progesterone production requires activation of caspase-3 in preovulatory
      granulosa cells in a serum starvation model.
AB  - Granulosa cells proliferate, differentiate, and undergo apoptosis throughout
      follicular development. Previous studies have demonstrated that stimulation of
      progesterone production is accompanied by caspase-3 activation. Moreover, we
      previously reported that arsenic enhanced caspase-3 activity coupled with
      progesterone production. Inhibition of caspase-3 activity can significantly
      inhibit progesterone production induced by arsenic or follicle-stimulating
      hormone (FSH). Here, we report that serum starvation induces caspase-3 activation
      coupled with augmentation of progesterone production. Serum starvation also
      increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme
      (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may
      contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition
      of caspase-3 activity resulted in a decrease in progesterone production.
      Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted
      in decreases in P450scc and StAR expression, which may partly contribute to the
      observed decrease in progesterone production. Our study demonstrates for the
      first time that progesterone production in preovulatory granulosa cells is
      required for caspase-3 activation in a serum starvation model. Inhibition of
      caspase-3 activity can result in decreased expression of the steroidogenic
      proteins P450scc and StAR. Our work provides further details on the relationship
      between caspase-3 activation and steroidogenesis and indicates that caspase-3
      plays a critical role in progesterone production by granulosa cells.

PMID- 22963863
TI  - Distinct expression of interleukin 17, tumor necrosis factor alpha, transforming
      growth factor beta, and forkhead box P3 in acute rejection after kidney
      transplantation.
AB  - The kidney transplant is the main therapeutic alternative for end-stage kidney
      disease, and rejection is a major complication. The expression of proinflammatory
      cytokines is related to graft loss, whereas anti-inflammatory cytokines are
      associated with graft protection. The objective of this study is to evaluate the
      "in situ" expression of cytokines T helper 1 (tumor necrosis factor alpha [TNF
      alpha]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell
      (transforming growth factor beta [TGF-beta]) and the expression of forkhead box
      P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in
      allograft kidney under rejection process by indirect immunohistochemistry.
      Eighteen renal graft biopsies were from patients with episodes of rejection. The
      in situ expression of IL-17, TNF-alpha, and TGF-beta was significantly higher in
      patients with acute rejection when compared with the control group. In contrast,
      analysis of FoxP3 expression showed few positive cells in patients with acute
      rejection compared with the control group. The results suggest that the
      expression of proinflammatory cytokines (IL-17 and TNF-alpha) contributes to the
      mechanisms of kidney transplant rejection. The increase in TGF-beta expression
      might be an attempt to establish a process of immunoregulation or even to induce
      higher production of IL-17. The last hypothesis is supported by the observation
      of a reduced expression of FoxP3 and elevated levels of IL-17.

PMID- 22963864
TI  - Effect of 5-azacytidine on in vitro biofilm formation of Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is a gram-positive bacterium that causes otitis media,
      pneumonia, meningitis and sepsis in young children and the elderly. Previous
      studies reported that pneumococci in different diseases do not behave as
      planktonic cells, but predominantly show characteristics of a biofilm. In this
      study we examine the effect of 5-azacytidine on S. pneumoniae, particularly on
      biofilm formation and investigate the gene expression involved in synthesis of
      autoinducer-2, competence and DNA repair. The effect of 5-aza on in vitro biofilm
      formation was studied by the crystal violet microtiter plate method. The S.
      pneumoniae biofilms were grown with different concentration of 5-azacytidine (15
      500 MUm), at variable time intervals and the inhibition percentages were
      calculated. The effects of 5-aza on the morphology of biofilms were analyzed by
      scanning electron microscope. The relative quantification of 11 genes of biofilms
      grown with 5-aza involved in autoinducer-2 synthesis, competence and DNA repair
      was carried out by real-time RT-PCR with respect to biofilms grown without 5-aza.
      The crystal violet microtiter assay detected a significant inhibitory effect of 5
      aza on in vitro biofilm formation, at concentration that did not inhibited
      planktonic cell growth. The SEM analysis demonstrated thin and disrupted
      biofilms, without micro-colonies in the samples treated with 5-aza, while these
      structures were present in the biofilms grown without 5-aza. The relative
      quantification of gene expression of 5-aza biofilms showed a significant down
      regulation of genes involved in the methionine and homocysteine recycling pathway
      which produces quorum sensing molecule autoinducer-2 as by-products. A
      significant decrease in the expressions of luxS, metK, pfs and cmK was detected.
      In conclusion, 5-aza inhibits in vitro biofilm formation and decreases the
      expression of luxS, pfs and metK, which are involved in the synthesis of
      autoinducer-2 as by-products of the methionine recycling pathway. The inhibitory
      effect of 5-aza may be either due to down regulation of pfs, luxS and metK or due
      to accumulation of the toxic substrate of pfs, luxS and metK genes.

PMID- 22963865
TI  - Partitioning of fluoranthene between free and bound forms in stormwater runoff
      and other urban discharges using passive dosing.
AB  - Partitioning of fluoranthene in stormwater runoff and other urban discharges was
      measured by a new analytical method based on passive dosing. Samples were
      collected at the inlet (n = 11) and outlet (n = 8) from a stormwater retention
      pond in Albertslund (Denmark), and for comparison samples were also obtained at a
      municipal wastewater treatment plant, a power plant, a contaminated site and a
      waste deposit in Copenhagen (n = 1 at each site). The freely dissolved
      concentration of (14)C-fluoranthene in the samples was controlled by equilibrium
      partitioning from a pre-loaded polymer and the total sample concentration
      measured. The measurements yielded free fractions of fluoranthene in stormwater
      in the range 0.04-0.15 in the inlet during the first part of the runoff events
      increasing to 0.3-0.5 at the end of the events and in the outlet from the
      retention pond. The enhanced capacity of the different stormwater samples for
      carrying fluoranthene was 2-23 relative to pure water and decreasing during rain
      events. The enhanced capacity of stormwater showed a different relationship with
      suspended solid concentrations than the other types of urban discharges.
      Partitioning of fluoranthene to dissolved organic carbon was lower than
      partitioning to particulate organic carbon. Partitioning of fluoranthene to
      particulate organic matter in the 19 stormwater samples yielded a log K(POM) of
      5.18. The presented results can be used in stormwater quality modeling and
      assessment of efficiency of stormwater treatment systems. This work also shows
      the potential of the passive dosing method to obtain conversion factors between
      total concentrations, which are needed for comparison with water quality
      criteria, and freely dissolved concentrations, which are more related to toxicity
      and obtained by the use of most passive samplers.

PMID- 22963866
TI  - Appraisal of chlorine contact tank modelling practices.
AB  - With new water directives imposing strict regulations to reduce the footprint of
      treatment operations and contaminant levels, a performance review of water
      treatment facilities, including Chlorine Contact Tanks (CCTs) is required. This
      paper includes a critical appraisal of the international literature on CCT
      modelling practices to date, aiming to assist the identification of areas
      requiring further development, in particular, relating to the computational
      modelling capability and availability of tools to assist hydraulic design and
      optimisation studies of CCTs. It notes that the hydraulic optimisation practice
      of poorly designed tanks commenced with experimental studies undertaken in the
      1960s and 1970s, which involved mainly two types of studies, namely in situ
      tracer tests and laboratory physical modelling. The former has traditionally been
      conducted to diagnose the hydraulic performance of existing CCTs, typically based
      on results such as Residence Time Distribution (RTD) curves and values of the
      Hydraulic Efficiency Indicators (HEIs). The latter has been useful in trial and
      error testing of the impact of certain design modifications on those results,
      with suggestions for later improvements of the field scale unit. In the 1980s
      mathematical and numerical modelling studies started to be used to assist CCT
      investigations, offering a greater level of detail in a more cost-effective
      manner than equivalent experimentally based investigations. With the growth of
      computing power and the popularisation of computational models, the 1990s saw the
      development and application of Computational Fluid Dynamics (CFD) tools to
      simulate the hydraulic performance of CCTs, sometimes independently of
      experimentation, other than by using available data to calibrate and validate
      modelling predictions. This has led to the current scenario of CFD models being
      invaluable assistive tools in optimisation studies of CCTs, with the
      experimentation practice continuing to allow for specific diagnostics and to
      supply data for the calibration and validation of CFD modelling results. The vast
      majority of CCT modelling studies published to date have focused on simulating
      CCT hydrodynamic and conservative solute transport processes. The chlorination
      kinetics and Disinfection By-Product (DBP) formation have rarely been
      contemplated in computer modelling studies of CCTs. Commercially available CFD
      models have not traditionally been applied with this purpose, while research
      studies undertaken using open source codes to produce tailor-made applications
      are rare. Aspects that could benefit from further understanding and/or
      development include the impact of scale when conducting experimentation with
      prototypes, adequate turbulence closure for a given situation, adequate numerical
      schemes vis-a-vis CFD model complexity vis-a-vis cost-benefit ratio of
      simulations and the inclusion of state of the art chlorination kinetics and DBP
      formation modelling in the CFD tools that can assist modern design and retrofit
      studies of CCTs.

PMID- 22963867
TI  - Spatial distribution and cognitive correlates of gamma noise power in
      schizophrenia.
AB  - BACKGROUND: Brain activity is less organized in patients with schizophrenia than
      in healthy controls (HC). Noise power (scalp-recorded electroencephalographic
      activity unlocked to stimuli) may be of use for studying this disorganization.
      Method Fifty-four patients with schizophrenia (29 minimally treated and 25 stable
      treated), 23 first-degree relatives and 27 HC underwent clinical and cognitive
      assessments and an electroencephalographic recording during an oddball P300
      paradigm to calculate noise power magnitude in the gamma band. We used a
      principal component analysis (PCA) to determine the factor structure of gamma
      noise power values across electrodes and the clinical and cognitive correlates of
      the resulting factors. RESULTS: The PCA revealed three noise power factors,
      roughly corresponding to the default mode network (DMN), frontal and occipital
      regions respectively. Patients showed higher gamma noise power loadings in the
      first factor when compared to HC and first-degree relatives. In the patients,
      frontal gamma noise factor scores related significantly and inversely to working
      memory and problem-solving performance. There were no associations with symptoms.
      CONCLUSIONS: There is an elevated gamma activity unrelated to task processing
      over regions coherent with the DMN topography in patients with schizophrenia. The
      same type of gamma activity over frontal regions is inversely related to
      performance in tasks with high involvement in these frontal areas. The idea of
      gamma noise as a possible biological marker for schizophrenia seems promising.
      Gamma noise might be of use in the study of underlying neurophysiological
      mechanisms involved in this disease.

PMID- 22963868
TI  - Electroclinical, MRI  and surgical outcomes in 100 epileptic patients with type
      II FCD.
AB  - Focal cortical dysplasias (FCDs) are highly epileptogenic malformations
      associated with drug-resistant epilepsy, susceptible to surgical treatment. Among
      the different types of FCD, the type II includes two subgroups based on the
      absence (IIa) or presence (IIb) of balloon cells. The aim of this retrospective
      study was to investigate possible differences in electroclinical presentations
      and surgical outcomes between the two subgroups in 100 consecutive surgically
      treated patients with type II FCDs. All patients underwent a comprehensive
      presurgical assessment including stereo-EEG (SEEG) when necessary. No significant
      differences in gender, age at epilepsy onset, duration of epilepsy, age at
      surgery or seizure frequency were found between the two subgroups. Patients with
      type IIb FCD frequently showed sleep-related epilepsy. Their peculiar
      electrographic pattern was characterised by localised rhythmic or pseudo-rhythmic
      spikes or polyspikes ("brushes") enhanced during non-REM sleep and also
      associated with well-localised, brief, low-voltage fast activity. The incidence
      and frequency of short bursts of fast discharges, interrupted by activity
      suppression, increased during slow-wave sleep and often recurred pseudo
      periodically. The occurrence of "brushes", present in 76% of the patients with
      type IIb FCD, was significantly associated (p<0.001) with the presence of balloon
      cells. We discuss the possible pathogenetic mechanisms underlying this activity.
      MRI diagnosis of type II FCD was made in 93% of the patients with balloon cells
      (BCs), suggesting that the presence of balloon cells might be, at least
      partially, responsible for the MRI features. Patients had very good postsurgical
      outcomes (83% in Engel class I) even after a long period of follow-up.

PMID- 22963869
TI  - Neonatal appendicitis mimicking intestinal duplication: a case report.
AB  - INTRODUCTION: Acute appendicitis is a common disease in older children but rare
      in neonates. CASE PRESENTATION: We report the case of a 2-day-old Asian baby who
      suffered from neonatal appendicitis mimicking intestinal duplication.
      Laparoscopic appendectomy was successfully performed after the trans-umbilical
      division of adhesions, and the postoperative course was uneventful. CONCLUSION:
      There are few reports describing abdominal masses caused by appendicitis
      mimicking intestinal duplication. The laparoscopic approach for neonatal
      appendicitis is considered to be a safe and useful therapeutic modality with good
      cosmetic results.

PMID- 22963870
TI  - miRNA regulates noncoding RNA: a noncanonical function model.
AB  - It has long been assumed that miRNAs can only target protein-coding mRNAs in the
      cytoplasm. Recent studies, however, reveal miRNAs are also transported from the
      cytoplasm to the nucleus, where they function in a noncanonical manner to
      regulate noncoding RNAs. Here, we highlight the working model of these
      noncanonical miRNAs.

PMID- 22963871
TI  - Pancreatitis from pigmented stone impaction of the minor duct in the setting of
      pancreas divisum.

PMID- 22963872
TI  - Repositioning of a misplaced self-expandable metal stent in an inoperable
      esophageal cancer with severe stricture.

PMID- 22963874
TI  - Low serum cultured adipose tissue-derived stromal cells ameliorate acute kidney
      injury in rats.
AB  - Current studies suggest that mesenchymal stromal cells (MSCs) improve acute
      kidney injury (AKI) via paracrine/endocrine effects. We established human adipose
      tissue-derived stromal cells (hASCs) cultured in low (2%) serum (hLASCs), which
      have great potential of tissue regeneration.  The present study was performed to
      investigate the therapeutic effects of hLASCs on AKI and to clarify the
      mechanisms involved. In low serum, hASCs proliferated well, while human bone
      marrow-derived stromal cells (hBMSCs) did not. hLASCs secreted higher levels of
      hepatocyte growth factor (HGF)  and vascular endothelial growth factor (VEGF)
      than did hASCs cultured in high (20%) serum (hHASCs) or hBMSCs cultured in high
      serum (hHBMSCs). AKI was induced in nude rats by folic acid, and hLASCs, hHASCs
      or control medium were administered into the renal subcapsules. hLASCs
      significantly  attenuated acute renal damage, while hHASCs showed far less
      effect. Furthermore, interstitial fibrosis observed on day 14 was less pronounced
      in the hLASCs group. Cell tracking experiment showed no evidence of
      transdifferentiation. Intravenous injection of hLASCs or hHBMSCs or subcapsular 
      injection of hHBMSCs did not ameliorate AKI. Concerning the mechanisms, our in
      vivo experiments showed that HGF knockdown by siRNA impaired the ability of
      hLASCs to protect the kidney from acute injury whereas VEGF knockdown did not. In
      conclusion, hLASCs, but not hHASCs or hHBMSCs, ameliorated  AKI via paracrine
      effects, and HGF is one of the key mediators.

PMID- 22963875
TI  - Double-chambered left ventricle plus left ventricular non-compaction: report of
      an abnormal association.

PMID- 22963873
TI  - Histone deacetylases and cancer.
AB  - Reversible acetylation of histone and non-histone proteins is one of the most
      abundant post-translational modifications in eukaryotic cells. Protein
      acetylation and deacetylation are achieved by the antagonistic actions of two
      families of enzymes, histone acetyltransferases (HATs) and histone deacetylases
      (HDACs). Aberrant protein acetylation, particularly on histones, has been related
      to cancer while abnormal expression of HDACs has been found in a broad range of
      cancer types. Therefore, HDACs have emerged as promising targets in cancer
      therapeutics, and the development of HDAC inhibitors (HDIs), a rapidly evolving
      area of clinical research. However, the contributions of specific HDACs to a
      given cancer type remain incompletely understood. The aim of this review is to
      summarize the current knowledge concerning the role of HDACs in cancer with
      special emphasis on what we have learned from the analysis of patient samples.

PMID- 22963876
TI  - Mitral stenosis and pedunculated left atrial thrombus: an unusual presentation.

PMID- 22963877
TI  - Contribution ratio of freely to total dissolved concentrations of polycyclic
      aromatic hydrocarbons in natural river waters.
AB  - The bioavailability and ecological risk of hydrophobic organic compounds (HOCs)
      in aquatic environments largely depends on their freely dissolved concentrations.
      In this work, the freely dissolved concentrations of polycyclic aromatic
      hydrocarbons (PAHs) including phenanthrene, pyrene, and chrysene were determined
      for the Yellow River, Haihe River and Yongding River of China using polyethylene
      devices (PEDs). The results indicated that the order of ratios of freely to total
      dissolved concentrations of the three PAHs was phenanthrene (66.8+/-20.1%)>pyrene
      (48.8+/-26.4%)>chrysene (5.5+/-3.3%) for the three rivers. The ratios were
      significantly negatively correlated with the logK(ow) values of the PAHs. In
      addition, the ratios were negatively correlated with the suspended sediment (SPS)
      and dissolved organic carbon (DOC) concentrations in the river water, and the
      characteristics of the SPS and DOC were also important factors. Simulation
      experiments showed that the ratio of freely to total dissolved concentrations of
      pyrene in the aqueous phase decreased with increasing SPS concentration; when the
      sediment concentration increased from 2 g L(-1) to 10 g L(-1), the ratio
      decreased from 67.6% to 38.4% for Yellow River sediment and decreased from 50.4%
      to 33.6% for Haihe River sediment. This was because with increasing SPS
      concentration, more and more DOC, small particles and colloids (<0.45 MUm) would
      enter the aqueous phase. Because high SPS and DOC concentrations exist in many
      rivers, their effect on the freely dissolved concentrations of HOCs should be
      considered when conducting an ecological risk assessment.

PMID- 22963878
TI  - Antibacterial and antifungal activities of polyketide metabolite from marine
      Streptomyces sp. AP-123 and its cytotoxic effect.
AB  - A Gram positive, filamentous, spore forming antagonistic Streptomyces sp. AP-123
      derived from marine region of Andra Pradesh, India, was studied for its medical
      importance. Among the 210 Streptomyces strains screened at 64.3% exhibited
      activity against Gram positive bacteria, 48.5% showed activity towards Gram
      negative bacteria, 38.8% exhibited both Gram positive and negative bacteria and
      80.85% strains revealed significant antifungal activity. However, primary
      screening revealed that Streptomyces sp. AP-123 exhibited significant
      antimicrobial activity against all the tested bacteria compared to other
      Streptomyces strains. The presence of l-diaminopimelic acid and glycine in the
      cell wall hydrolysates and streptomycin resistance indicated the strain belonged
      to Streptomyces genus. The 16S rDNA gene based phylogenetic affiliation was
      determined by using bioinformatic tools and it was identified as Streptomyces sp.
      AP-123 with 99% sequence similarity to Streptomyces flavogriseus. The
      antimicrobial substances were extracted by hexane and ethyl acetate from spent
      medium in which Streptomyces sp. AP-123 was cultivated at 30  degrees C for 5 d.
      The antimicrobial activity was assessed using broth micro-dilution technique. A
      compound was obtained by eluting the crude extract using varying concentrations
      of solvents followed by the chromatographic purification. Based on the IR, (13)C
      NMR and (1)H NMR spectral data, the compound was identified as polyketide related
      antibiotic. It exhibited significant antibacterial activity against Gram positive
      and Gram negative bacteria and also showed a potent cytotoxic activity against
      cell lines viz. Vero (Green monkey kidney) and HEP2 (laryngeal carcinoma cells)
      in vitro. The lowest Minimum Inhibitory Concentration (MIC) of the compound
      against Bacillus subtilis and Staphylococcus aureus were 25 and 37.5 MUg mL(-1),
      respectively. Against Escherichia coli and Pseudomonas aeruginosa it exhibited
      MIC of 50 and 37.58 MUg mL(-1), respectively. However, against Candida albicans
      and filamentous fungus, Aspergillus niger the MIC values were 12.5 and 25 MUg mL(
      1), respectively. Cloning and sequence analysis of ketoacyl synthase (KS) gene
      revealed similarity to the type II polyketide synthase (PKS) gene of Streptomyces
      species.

PMID- 22963879
TI  - Inhibitory effects of carbon nanotubes on the degradation of 14C-2,4
      dichlorophenol in soil.
AB  - Concerns on the potential risks of engineered nanoparticles to the environment
      are increasing; however, little is known about the effects of carbon nanotubes
      (CNTs) on the environmental fate of hydrophobic organic pollutants in soil. We
      incubated radioactive labeled 2,4-dichlorophenol ((14)C-2,4-DCP) in a soil in the
      presence of various concentrations (0, 2, 20, and 2000 mg kg(-1) dry soil) of
      single-walled (SWCNTs) and multi-walled (MWCNTs) carbon nanotubes, and determined
      the mineralization, degradation, and residue distribution of 2,4-DCP in the soil.
      CNTs were added to the soil either after the spiking of (14)C-2,4-DCP or together
      with (14)C-2,4-DCP as a mixture. CNTs at the concentration of 2000 mg kg(-1)
      significantly (P<0.05) inhibited the mineralization of (14)C-2,4-DCP and induced
      a 2.3- to 3.9-fold increase in the amounts of the non-degraded (14)C-2,4-DCP in
      the soil after 90 d of incubation. Pre-adsorption of (14)C-2,4-DCP on CNTs showed
      stronger inhibitory effects on the degradation of (14)C-2,4-DCP, already
      significant with CNTs at 20 mg kg(-1). In general, SWCNTs had a higher effect on
      the degradation and residue distribution of 2,4-DCP in the soil than MWCNTs. The
      inhibitory effects are supposed to be owing to limited activities of soil
      endogenous microorganisms, potential toxicities of CNTs to the microorganisms,
      and reduced bioavailability of 2,4-DCP in the presence of CNTs, even though a
      desorption hysteresis of 2,4-DCP on CNTs was not observed. Our results indicate
      that CNTs have more significant impacts on the environmental fate of the
      hydrophobic pollutants entering soil together with CNTs via strong sorption than
      the pollutants already present in soil.

PMID- 22963880
TI  - Long-term olive oil-based parenteral nutrition sustains innate immune function in
      home patients without active underlying disease.
AB  - BACKGROUND & AIMS: It remains unclear whether impaired host defenses contribute
      to the increased risk for infectious complications seen in patients on home
      parenteral nutrition (HPN). The aim of this study was to compare the innate
      immune function of patients on olive oil-based HPN with that of healthy controls.
      METHODS: Innate immune functions and (anti-)oxidant balance were studied in 20
      patients on olive oil-based HPN without an active underlying immune-mediated
      disease (Clinoleic((r)), >= 6 months; >3 times/week), and 21 age- and sex-matched
      healthy controls. RESULTS: Neutrophils of patients and controls had a similar
      capacity to eliminate Streptococcus pneumoniae. Also, levels of activation
      markers (CD66b, CD11b, CD62L) in granulocytes and monocytes, phorbol ester- and
      zymosan-induced neutrophil oxygen radical production were not different between
      patients and controls. No differences in (anti-)oxidant status were found, except
      for higher concentrations of oxidized glutathione and lower plasma selenium and
      vitamin C in patients compared to controls. CONCLUSION: Compromised innate immune
      function does not seem to explain the increased risk for infectious complications
      in HPN patients using olive oil-based lipid emulsions.

PMID- 22963881
TI  - Effects of metformin on markers of oxidative stress and antioxidant reserve in
      patients with newly diagnosed type 2 diabetes: a randomized clinical trial.
AB  - BACKGROUND & AIMS: Given the long term benefits observed with metformin use in
      diabetes patients, a role in modulating oxidative stress is imputable. Effects of
      metformin on markers of oxidative stress, antioxidant reserve, and HDL-c
      associated antioxidant enzymes were investigated. METHODS: In a clinical trial
      setting (Registered under Clinical Trials.gov Identifier no. NCT01521624) 99
      medication-naive, newly diagnosed type 2 diabetes patients were randomly assigned
      to either metformin or lifestyle modification. AOPP, AGE, FRAP, activities of
      LCAT, and PON were measured at baseline and after 12-weeks. RESULTS: Baseline
      values of the oxidative stress markers did not differ significantly between the
      two groups. In cases, after three months treatment, there was a significant
      reduction in AOPP (137.52 +/- 25.59, 118.45 +/- 38.42, p < 0.001), and AGE (69.28
      +/- 4.58, 64.31 +/- 8.64, p = 0.002). FRAP and PON increased significantly
      (1060.67 +/- 226.69, 1347.80 +/- 251.40, p < 0.001 and 29.85 +/- 23.18, 37.86 +/-
      27.60, p = 0.012 respectively). LCAT levels remained unchanged (45.23 +/- 4.95,
      46.15 +/- 6.28, p = 0.439). Comparing the two groups in a final multivariate
      model, AOPP, FRAP, and AGE levels changed more significantly in metformin
      compared with lifestyle modification alone (p = 0.007, p < 0.001 and p < 0.001
      respectively). Escalation in LCAT or PON activities did not differ between the
      two groups (p = 0.199 and 0.843 respectively). CONCLUSIONS: Use of metformin is
      more effective in reducing oxidative stress compared with lifestyle modification
      alone.

PMID- 22963882
TI  - Number of CAG repeats in POLG1 and its association with Parkinson disease in the
      Norwegian population.
AB  - The number of CAG repeats in the mitochondrial DNA-polymerase gamma (POLG1) gene
      has been associated with Parkinson disease (PD) in some populations. We sequenced
      the CAG tract of POLG1 in 191 Norwegian patients with PD and an equal number of
      controls and found an association between non-10 or 11 CAG repeats and PD in our
      population. While our results were significant, this trend was not maintained
      following correction for multiple testing. We also performed a meta-analysis of
      all published studies including our own that shows PD is associated with the
      number of CAG repeats in POLG1. The meta-analysis reveals that the rare allelic
      variation encompassed by non-10 CAG repeats associates significantly with PD
      (p=0.0017). Whether this reflects a direct influence of POLG on the pathogenesis
      of PD or linkage disequilibrium between POLG1 alleles and nearby, disease
      influencing genetic variants remains unknown.

PMID- 22963883
TI  - Piling up healthy behaviors.

PMID- 22963884
TI  - Genome-wide association studies of obesity and metabolic syndrome.
AB  - Until just a few years ago, the genetic determinants of obesity and metabolic
      syndrome were largely unknown, with the exception of a few forms of monogenic
      extreme obesity. Since genome-wide association studies (GWAS) became available,
      large advances have been made. The first single nucleotide polymorphism robustly
      associated with increased body mass index (BMI) was in 2007 mapped to a gene with
      for the time unknown function. This gene, now known as fat mass and obesity
      associated (FTO) has been repeatedly replicated in several ethnicities and is
      affecting obesity by regulating appetite. Since the first report from a GWAS of
      obesity, an increasing number of markers have been shown to be associated with
      BMI, other measures of obesity or fat distribution and metabolic syndrome. This
      systematic review of obesity GWAS will summarize genome-wide significant findings
      for obesity and metabolic syndrome and briefly give a few suggestions of what is
      to be expected in the next few years. 

PMID- 22963885
TI  - Estrogens promote cell-cell adhesion of normal and malignant mammary cells
      through increased desmosome formation.
AB  - The association of estrogen receptor alpha (ERalpha) expression with
      differentiated breast tumors presenting a lower metastasis risk could be
      explained by the estrogen modulation of cell adhesion, motility and invasiveness.
      Since desmosomes play a crucial role in cell-cell adhesion and may interfere in
      tumor progression, we studied their regulation by estrogens in human breast
      cancer and normal mammary cells. Estrogens increased the formation of desmosomes
      in normal and malignant cells. Furthermore, four desmosomal proteins
      (desmocollin, gamma-catenin, plakophilin and desmoplakin) appeared significantly
      up-regulated by estrogens in three ERalpha-expressing cancer cell lines and this
      effect was reversed by a pure antiestrogen. Finally, silencing of ERalpha or
      desmoplakin expression by specific siRNA revealed that estrogen-modulated
      desmosomal proteins are essential for the estrogenic control of intercellular
      adhesion. This estrogen modulation of desmosome formation could contribute to the
      lower invasiveness of ERalpha-positive tumors and to the integrity of epithelial
      layers in estrogen target tissues.

PMID- 22963886
TI  - Cortisol regulates Na+ uptake in zebrafish, Danio rerio, larvae via the
      glucocorticoid receptor.
AB  - Unlike other freshwater fish previously examined, zebrafish are capable of
      increasing their rate of Na(+) uptake during chronic exposure to acidic water (pH
      4). In the present study, the potential role of cortisol in the induction of
      Na(+) uptake during acid-exposure was investigated. When zebrafish larvae (4 days
      post-fertilization) were treated with waterborne cortisol, the rate of Na(+)
      uptake was significantly increased; this effect was blocked by co-incubating
      larvae with RU-486, an antagonist selective for the glucocorticoid receptor (GR).
      A similar induction in Na(+) uptake, which was also blocked by RU-486, was
      observed when larvae were treated with dexamethasone, a selective GR agonist.
      Conversely, treating larvae with aldosterone, a selective agonist for the
      mineralocorticoid receptor (MR) had no effect on Na(+) uptake. Acid-exposure
      increased whole body cortisol levels and translational knockdown of GR using
      antisense morpholinos prevented the full induction of Na(+) uptake during
      exposure to acidic water, further confirming the role of cortisol and GR in Na(+)
      uptake stimulation. Using immunohistochemistry, GR was localized to ionocytes
      known to be responsible for Na(+) uptake (HR-cells). Knockdown of Rhcg1, an
      apical membrane ammonia channel or Na(+)/H(+) exchanger 3b (NHE3b), proteins
      known to play an important role in facilitating Na(+) uptake in acidic water,
      prevented the stimulatory effects of cortisol treatment on Na(+) uptake,
      suggesting that cortisol regulates Na(+) uptake by stimulating an Rhcg1-NHE3b
      "functional metabolon".

PMID- 22963887
TI  - Detection of common mutations in the GALT gene through ARMS.
AB  - Type I galactosemia is an inborn error resulting from mutations on both alleles
      of the GALT gene, which leads to the absence or deficiency of galactose-1
      phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the
      conversion of galactose into glucose. On the basis of residual GALT activity,
      Type I galactosemia is classified into severe "Classical" and mild "Duarte"
      phenotypes. Classical galactosemia is frequently associated with S135L, Q188R and
      K285N mutations in the GALT gene. The functionally neutral N314D variation in the
      GALT gene is associated with Duarte galactosemia and is widespread among various
      worldwide populations. The present study aimed at detecting S135L, Q188R and
      K285N mutations and the N314D variant in the GALT gene by PCR using amplification
      refractory mutation system (ARMS). ARMS assays were established using standard
      DNA samples and were used for 8 galactosemia patients and 190 unrelated normal
      subjects all of Pakistani origin. S135L and K285N mutations were present neither
      in galactosemia patients nor in normal subjects. Only one galactosemia patient
      carried Q188R mutation that was in homozygous state. However, the N314D variant
      was frequently found both in affected (7 out of 16 alleles) and normal subjects
      (55 out of 380 alleles). This finding indicates that Duarte allele D314 might be
      far more common in Pakistani population than in European and North American ones.

PMID- 22963888
TI  - Readmission of known MRSA carriers and MRSA colonization pressure in hospital.
AB  - Readmission of asymptomatic methicillin-resistant Staphylococcus aureus (MRSA)
      carriers may contribute to the hospital reservoir. Using an electronic alert
      system, we assessed the weight of readmission of known MRSA carriers on MRSA
      colonization pressure in a hospital setting. During the 2004-2010 period, 2058
      alerts were generated for 1060 inpatients. A total of 486/1060 patients (46%)
      were readmitted at least once, and 330/486 (64.4%) were readmitted <3 months
      after discharge. A mean of 20 MRSA patients were present on the same day (from 40
      in 2004 to eight in 2010). The number of MRSA patient-days was 34 575, i.e. 2.5%
      of the 1 366 277 patient-days of the study period, and 17 737 (51.3%) MRSA
      patient-days were due to readmission of known MRSA carriers. The number of new
      MRSA cases was partly correlated with the number of MRSA patients hospitalized (R
      2 = 0.49). Rapid electronic identification of these patients proved essential in
      decreasing the global burden of MRSA in our hospital.

PMID- 22963889
TI  - Improving care and wellness in bipolar disorder: origins, evolution and future
      directions of a collaborative knowledge exchange network.
AB  - The Collaborative RESearch team to study psychosocial factors in bipolar
      disorder (CREST.BD) is a multidisciplinary, cross-sectoral network dedicated to
      both fundamental research and knowledge exchange on bipolar disorder (BD). The
      core mission of the network is to advance the science and understanding of
      psychological and social issues associated with BD, improve the care and wellness
      of people living with BD, and strengthen services and supports for these
      individuals. CREST.BD bridges traditional and newer research approaches,
      particularly embracing community-based participatory research (CBPR) methods.
      Membership of CREST is broad, including academic researchers, people with BD,
      their family members and supports, and a variety of health care providers. Here,
      we describe the origins, evolution, approach to planning and evaluation and
      future vision for our network within the landscape of CBPR and integrated
      knowledge translation (KT), and explore the keys and challenges to success we
      have encountered working within this framework.

PMID- 22963890
TI  - Hybrid stereoisomers of a compact molecular probe based on a jasmonic acid
      glucoside: syntheses and biological evaluations.
AB  - 12-O-beta-D-glucopyranosyl jasmonic acid (JAG) shows unique biological
      activities, including leaf-closing of Samanea saman. It is expected that the mode
      of action for such regulation is distinct from that of other jasmonates. We
      developed high-performance compact molecular probes (CMPs) based on JAG that can
      be used for the FLAG-tagging of JAG target. We synthesized four hybrid-type JAG
      CMP stereoisomers (7, ent-7, 8, and ent-8), which are composed of (-)-12-OH-JA
      (2)/D-galactopyranoside, (-)-2/L-galactopyranoside, (+)-ent-2/d
      galactopyranoside, and (+)-ent-2/L-galactopyranoside moieties, respectively, and
      we examined their biological features, such as the stereospecific induction of
      shrinkage, rate of the cellular response, and dependence on potassium channel
      activity. These features of the JAG-CMPs were completely consistent with those of
      the original JAG. These results indicate the biological equivalence of JAG and
      the JAG-CMPs. During the course of such biological evaluations, it was revealed
      that the biological activity of the CMPs is greatly dependent on the d/l
      stereochemistry of a glycon moiety. To the best of our knowledge, this is the
      first study suggesting that the d/l-stereochemistry of the glycon moiety
      significantly affects the biological activity of the associated glycoside.

PMID- 22963891
TI  - [A retrospective cohort study of patients diagnosed of thyroid cancer in the
      southwest Madrid area. Predictive factors in differentiated thyroid cancer].
AB  - OBJECTIVES: To analyze the clinical and histopathological features of patients
      with thyroid cancer in the southwest Madrid area and to identify poor prognostic
      factors in the subgroup with differentiated thyroid carcinoma (DTC) of the
      follicular epitelium. PATIENTS AND METHODS: A retrospective cohort study of
      patients diagnosed with thyroid cancer at our hospital from 1998 to 2009.
      Significant clinical, surgical, and histopathological variables were included in
      Cox proportional hazard and logistic regression models to identify baseline
      factors predicting for death, recurrence, and persistent disease in DTC. RESULTS:
      A total of 150 patients with a median age of 49 years and a median follow-up of
      5.4 years were enrolled. Histological subtypes were: papillary carcinoma (86%),
      follicular carcinoma (6.6%), medullary carcinoma (4%), poorly differentiated
      carcinoma (2.7%), and anaplastic carcinoma (0.7%). At the end of the study, 68%
      of patients were cured, 3.3% had died (disease-specific mortality, 1.3%), 1.3%
      were lost to follow-up, 6.7% had persistent biochemical disease, and 2.7%
      persistent clinical disease, while 18% of patients were pending assessment. The
      best prognostic model for DTC recurrence was TNM staging (stage II-IV vs. I: HR
      5.9, 95% CI 1.3-26.6), while the best model for persistent disease or death was
      ETA clinical staging (high risk vs. low or very low risk: OR 9.2, 95% CI 2.6
      33.2). CONCLUSIONS: In our study, disease-specific mortality and persistent
      clinical disease were low. Classification of DTC patients based on ETA staging
      after initial treatment was a good predictor of persistent disease or death.

PMID- 22963892
TI  - Heterogeneous trajectories of depressive symptoms: adolescent predictors and
      adult outcomes.
AB  - BACKGROUND: Depressive symptoms display heterogeneous trajectories across
      adolescence and early adulthood. Identifying risk and protective factors for
      distinct trajectory groups, and their respective outcomes, may provide insight
      into the etiological underpinnings of different symptom courses and inform the
      targets and timing of intervention. METHODS: A school-based sample of 719
      adolescents completed four diagnostic evaluations and up to 7 annually mailed
      questionnaires assessing psychiatric symptoms and psychosocial risk and
      protective factors. Parental history of psychiatric disorder was assessed. Growth
      mixture modeling (GMM) was used to identify latent depressive symptom
      trajectories from mid-adolescence through age 30, as well as their predictors in
      mid-adolescence and adult outcomes. RESULTS: A three class model consisting of
      high stable (32%), moderate decreasing (44%), and low decreasing (24%) depressive
      symptom trajectories emerged as the preferred solution. Demographic,
      psychosocial, and psychiatric characteristics differentiated the low and high
      symptom classes, and provided support for interpersonal models of depression
      chronicity. Members of the moderate and high symptom classes evidenced the worst
      psychosocial and psychiatric outcomes by age 30, with members of the high symptom
      class showing the greatest levels of impairment. LIMITATIONS: Cross-sectional
      measurement and floor effects of several predictor variables may have obscured
      the relations between those predictors and trajectory class membership.
      CONCLUSION: These findings suggest that prevention and intervention strategies
      may specifically target young women and those who experience poor interpersonal
      functioning in an effort to alter the course of depressive symptoms through early
      adulthood.

PMID- 22963893
TI  - Executive functioning among patients with borderline personality disorder (BPD)
      and their relatives.
AB  - BACKGROUND: Studies focusing on executive functioning in patients with borderline
      personality disorder (BPD) have shown divergent results. Moreover, little
      attention has been paid to the potential role of deficits in executive functions
      as markers of familial vulnerability to BPD. Thus, the aim of the present study
      was to investigate executive functions in both patients BPD and their unaffected
      first-degree relatives (parents). METHOD: We examined executive functions in four
      groups: patients with BPD (n=27), age-matched healthy controls (n=29), healthy
      unaffected parents of patients in the BPD group (n=20) and their respective age
      matched controls (n=22). We administered tests that tapped three domains of
      executive functions: cognitive planning, sustained attention, and spatial working
      memory. All tests form part of the Cambridge Neuropsychological Test Automated
      Battery (CANTAB) battery. RESULTS: BPD patients displayed deficient executive
      functioning as compared to healthy controls in the domains of cognitive planning,
      sustained attention and working memory. Both BPD patients and their parents
      showed reduced latency to initiate the first move on the planning task [CANTAB's
      Tower of London]. All other measurements of executive functions did not differ
      significantly between parents of BPD patients and their respective healthy
      controls. LIMITATION: Results should be replicated with a larger sample size.
      CONCLUSIONS: BPD patients demonstrate a generalized profile of executive
      dysfunction. In the group comprising their parents, however, we found a lack of
      evidence for executive dysfunctions. Hence, executive dysfunctions do not appear
      to be markers of familial vulnerability for BPD.

PMID- 22963894
TI  - A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for
      the treatment of insomnia and mood stability in patients with euthymic bipolar
      disorder.
AB  - BACKGROUND: Abnormalities in circadian rhythms are prominent features of bipolar
      disorder. Disrupted circadian rhythms are associated with an increased risk of
      relapse in bipolar disorder. Normalizing the circadian rhythm pattern of bipolar
      patients may improve their sleep and lead to fewer mood exacerbations. This study
      evaluated adjunctive ramelteon for the treatment of insomnia and mood stability
      in euthymic bipolar patients. METHODS: Participants with euthymic bipolar
      disorder and sleep disturbances were randomized to receive adjunctive ramelteon
      or placebo in addition to their regular psychiatric medications for up to 24
      weeks or until they experienced a relapse (defined as a depressed or manic
      event). RESULTS: 83 participants were randomized to receive ramelteon (n=42) or
      placebo (n=41). Forty participants relapsed (48.2%). Cox regression analyses
      indicated that participants who received ramelteon (odds ratio 0.48, p=.024) were
      less likely to relapse. Kaplan Meier curves also indicated longer median survival
      times in the ramelteon group (Mdn=188 days) versus the placebo group (Mdn=84
      days) X2(1)=5.33, p=.02. There were no serious adverse events in this study.
      LIMITATIONS: This was a small study with only 83 participants. The one-week
      window of confirmed stability is shorter than time intervals used in other
      studies. CONCLUSIONS: The present study shows that ramelteon was effective in
      maintaining stability for individuals with bipolar disorder. Patients treated
      with ramelteon were approximately half as likely to relapse as patients treated
      with placebo throughout the 24-week treatment period.

PMID- 22963895
TI  - The relationship between affective temperaments, defensive styles and depressive
      symptoms in a large sample.
AB  - BACKGROUND: Affective temperaments may represent heritable subclinical
      manifestations of mood disorders. The concept of ego defense mechanisms also has
      provided a model for the comprehension of mood psychopathology. The relationships
      between affective temperaments, defense styles and depressive symptoms remain
      unknown. METHODS: We obtained data from a subsample of the Brazilian Internet
      Study on Temperament and Psychopathology (BRAINSTEP). Socio-demographic
      information was collected and participants completed the Affective and Emotional
      Temperament Composite Scale (AFECTS), the defense style questionnaire (DSQ-40)
      and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: Among 9937 participants
      (4472 male; 45%), individuals with hyperthymic or euthymic temperaments were more
      likely to present a mature defense style, whereas an immature defensive style was
      predominantly observed in individuals with cyclothymic, volatile, depressive,
      dysphoric, euphoric and disinhibited temperaments. Higher immature and lower
      mature defense style scores were independently associated with depressive
      symptoms. Participants with either euthymic or hyperthymic temperaments were less
      likely to endorse depressive symptoms. Euthymic and hyperthymic temperaments
      moderated the correlations of mature/immature defenses with depressive symptoms.
      LIMITATIONS: The data was collected from a convenience web-based sample. The
      study was cross-sectional. CONCLUSIONS: Affective temperaments are associated
      with distinct defense styles. These two personality theories provide distinct but
      interacting views for comprehension of depressive psychopathology.

PMID- 22963896
TI  - Selective serotonin reuptake inhibitors and tricyclic antidepressants in the
      acute treatment of chronic depression and dysthymia: a systematic review and meta
      analysis.
AB  - INTRODUCTION: Chronic depression represents a substantial portion of depressive
      disorders and is associated with severe consequences. This review examined the
      efficacy and acceptability of selective serotonin reuptake inhibitors (SSRIs) and
      tricyclic antidepressants (TCAs) in the treatment of chronic depression.
      Additionally, the comparative effectiveness of the two types of antidepressants
      has been examined. METHODS: A systematic search was conducted in the following
      databases: CENTRAL, MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and
      CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance
      outcome was dropping out of the study. Only randomized controlled trials were
      considered. RESULTS: We identified 20 studies with 22 relevant comparisons. 19
      studies focused on samples with a majority of dysthymic patients. Both SSRIs and
      TCAs are efficacious in terms of response rates when compared to placebo (Benefit
      Ratio [BR]=1.49; p<0.001 for SSRIs and BR=1.74; p<0.001 for TCAs) and no
      statistically significant differences between the active drugs and placebo in
      terms of dropout rates could be found. No differences in effectiveness were found
      between SSRIs and TCAs in terms of response rates (BR=1.01; p=0.91), yet, SSRIs
      showed statistically better acceptability in terms of dropout rates than TCAs
      (Odds Ratio [OR]=0.41; p=0.02). LIMITATIONS: The methodological quality of the
      primary studies was evaluated as unclear in many cases and more evidence is
      needed to assess the efficacy of SSRIs and TCAs in patients suffering from
      chronic forms of depression other than dysthymia. CONCLUSIONS: This systematic
      review provides evidence for the efficacy of both SSRIs and TCAs in the treatment
      of chronic depression and showed a better acceptability of SSRIs.

PMID- 22963897
TI  - Type A behavior pattern: Bortner scale vs. Japanese-original questionnaires.
AB  - BACKGROUND: Type A behavior pattern (TABP) has been regarded as a putative risk
      factor for coronary heart disease and recent studies from our group suggest that
      TABP individuals, identified via the Bortner scale whose validity had been
      confirmed by structured interviews, may have a greater tendency towards
      hyperthymic temperament, shorter sleep time and shorter snooze time. Since the
      Bortner scale was developed in USA and may reflect western culture, it is
      necessary to reconfirm our findings using a Japanese questionnaire such as
      Coronary-prone Type Scale for Japanese (CTS) and Kwansei Gakuin's daily life
      questionnaire (KG questionnaire). METHODS: Fifty healthy subjects were assessed
      for TABP using the Bortner scale, as well as the CTS and KG questionnaires.
      Hyperthymic temperament was assessed via the Japanese standardized version of the
      Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire
      (TEMPS-A), while sleep time and snooze time were measured by actigraphy. RESULTS:
      Both CTS and KG questionnaire scores were significantly and positively associated
      with the Bortner scale scores. Although CTS and KG scores were significantly and
      positively associated with hyperthymic temperament scores, none were associated
      with sleep time or snooze time. LIMITATIONS: The number of subjects was
      relatively small. CONCLUSIONS: The findings suggest that Japanese questionnaires
      such as CTS and KG questionnaires are valid as measures of TABP. Moreover, the
      association between TABP and hyperthymic temperament was reconfirmed by both CTS
      and KG questionnaires, whereas the association between TABP and sleep pattern was
      not. As such, the present findings provide supportive evidence about the
      usefulness of CTS and KG questionnaires.

PMID- 22963898
TI  - Corpus callosal morphology in early onset adolescent depression.
AB  - BACKGROUND: Abnormalities in the corpus callosum and related white matter
      projections have been implicated in major depressive disorder (MDD). Although MDD
      is as common in adolescence as in adulthood, few studies have examined youth near
      illness onset in order to determine the possible influence of atypical
      development on the pathophysiology of this disorder. MATERIALS AND METHODS: The
      area of the corpus callosum and its sub-regions were measured in 16 subjects
      affected by MDD (16.24 +/- 2.03 years) and 16 age- and sex-matched healthy
      controls (16.52 +/- 2.20 years) using magnetic resonance imagine (MRI). RESULTS:
      Mann-Whitney U-tests revealed a difference in corpus callosal areas (u=75.00,
      p=0.047). Corpus callosal area was smaller in MDD participants (5.92 +/- 0.50
      cm(2)) as compared to age and sex matched controls (6.44 +/- 0.75 cm(2)). This
      difference was isolated to the genu (U=62.00, p=0.012; 2.53 +/- 0.34 cm(2) for
      controls and 2.24 +/- 0.20 cm(2) for MDD participants), with no other sub-region
      demonstrating a significant difference. There was no difference in intracranial
      area between groups. No structure correlated with clinical or demographic
      variables. LIMITATIONS: Confirmation and extension of our findings requires a
      larger sample size and usage of diffusion tensor imaging. CONCLUSIONS: While
      preliminary, our findings provide new evidence of abnormalities in the genu of
      the corpus callosum in early onset depression.

PMID- 22963899
TI  - Deficits in emotion recognition in pediatric bipolar disorder: the mediating
      effects of irritability.
AB  - BACKGROUND: Pediatric Bipolar Disorder (PBD) is a debilitating condition
      associated with impairment in many domains. Social functioning is one of the
      disorder's most notable areas of impairment and this deficit may be in part due
      to difficulties recognizing affect in others. METHODS: In the present study,
      medication naive youth with PBD were compared to age-matched healthy controls on
      their ability to (a) distinguish between categorical emotions, such as happiness,
      anger, and sadness on the Emotion Recognition Test (ER-40) and (b) differentiate
      between levels of emotional intensity on an adapted version of the Penn Emotional
      Acuity Task (Chicago-PEAT). RESULTS: Results indicated that PBD youth
      misidentified sad, fearful, and neutral faces more often than controls, and PBD
      girls mislabeled 'very angry' faces more often than healthy girls. A mediation
      analyses indicated that these diagnostic group differences on emotion recognition
      were significantly mediated by irritability. LIMITATIONS: The Chicago-PEAT only
      examined variations in emotional intensity for the emotions happy and anger.
      Additionally, all results are correlational; therefore causal inferences cannot
      be made. CONCLUSIONS: Supporting previous literature, the present findings
      highlight the importance of emotion recognition deficits in PBD individuals.
      Additionally, the irritability associated with PBD may be an important mechanism
      of this deficit and may thus represent an important target for treatment.

PMID- 22963900
TI  - Ambulatory EEG: a cost-effective alternative to inpatient video-EEG in adult
      patients.
AB  - INTRODUCTION: Ambulatory electroencephalography (AEEG) is a monitoring technique
      that allows the recording of continuous EEG activity when patients are at home,
      without the necessity of admission to the hospital for prolonged video-EEG
      monitoring. METHODS: This is a prospective cohort study performed in a Canadian
      academic centre in order to assess the yield and tolerability of AEEG in the
      adult population. Over a period of three years, 101 patients were included. The
      yield of AEEG was assessed by taking into account the questions asked by the
      clinician before and after the investigation. RESULTS: One hundred and one
      patients undergoing AEEG were prospectively recruited during a three-year-period.
      Our population consisted of 45 males (44.6%) and 56 females (55.4%). The mean age
      of the group was 36.6 +/- 16.1 years. Most of the patients had at least one
      previous routine EEG (93%). The primary reasons for the AEEGs were subdivided
      into four categories: a) to differentiate between seizures and non-epileptic
      events; b) to determine the frequency of seizures and epileptiform discharges; c)
      to characterize seizure type or localization; and d) to potentially diagnose
      epilepsy. The mean duration of AEEG recording was 32 +/- 17 hours (15-96 hours).
      For 73 (72%) patients, the AEEG provided information that was useful for the
      management. For 28 (28%) patients, the AEEG did not provide information on
      diagnosis because no events or epileptiform activity occurred. In only 1 patient
      was the AEEG inconclusive due to non-physiological artefacts. Three patients were
      referred for epilepsy surgery without the necessity of video-EEG telemetry.
      CONCLUSION: In this study, we found that AEEG has a high diagnostic yield (72%)
      and believe that careful selection of patients is the most important factor for a
      high diagnostic yield. The main use of AEEG is the characterization of patients
      with non-epileptic events, in patients with a diagnosis of epilepsy that is not
      clear, and quantification of spikes and seizures to improve the medical
      management. Ambulatory EEG is a cost-effective solution for increasing demands
      for in-hospital video-EEG monitoring of adult patients.

PMID- 22963901
TI  - Preface.

PMID- 22963902
TI  - An aetiology of hominin behaviour.
AB  - A rough framework for a first attempt to formulate a preliminary aetiology of
      hominin behaviour is proposed, based on scientific rather than archaeological
      evidence and reasoning. Distinctive precursors of modernity in human behaviour
      were present several million years ago, and since then have become gradually more
      established. By the beginning of the Middle Pleistocene, modern human cognitive
      processes seem to have been largely established. However, full modernity of
      behaviour can only have occurred in recent centuries, and there remain great
      variations in it even among extant conspecifics. This model differs significantly
      from all narratives offered by mainstream archaeology, which generally place the
      advent of modern human behaviour 30 or 40 millennia ago. These notions and the
      hypotheses they are based on appear to be false, however such behaviour is
      defined.

PMID- 22963903
TI  - Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma:
      a review and update.
AB  - A large number of immunohistochemical markers that can assist in the differential
      diagnosis of epithelioid mesotheliomas are currently available. Because these
      markers are expressed differently in the various types of carcinomas that can
      metastasize to the serosal membranes and can potentially be confused with
      epithelioid mesothelioma, their selection for inclusion in a diagnostic panel
      largely depends on the differential diagnosis, as well as on which ones work the
      best in a given laboratory. Traditionally, the panels used in the differential
      diagnosis of epithelioid mesothelioma have consisted of a combination of positive
      mesothelioma markers and broad-spectrum carcinoma markers. At present, a wide
      variety of organ-associated carcinoma markers such as thyroid transcription
      factor-1 and napsin A for the lung, PAX 8 and PAX 2 for the kidney, and Mullerian
      derived tumors; gross cystic disease fluid protein-15 and mammaglobin for the
      breast; and CDX2 for intestinal differentiation are available, which can assist
      in establishing the site of origin of an adenocarcinoma when included in a
      diagnostic panel. This article provides updated information on the composition of
      the panels of markers recommended in the various differential diagnoses.

PMID- 22963904
TI  - Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes
      patients with graft dysfunction after allogeneic islet transplantation.
AB  - Islet transplantation is one of the most promising therapies for type 1 diabetes
      (T1D). A major issue in islet transplantation is the loss of graft function at
      late phase. Several studies suggested the involvement of islet-specific T-cells
      in such islet graft dysfunction. In this study,  we investigated the breadth and
      type of glutamic acid decarboxylase 65 (GAD65)-specific T-cells in T1D patients
      after allogeneic islet transplantation. Peripheral blood mononuclear cells
      (PBMCs) were obtained from islet-transplanted T1D patients during insulin
      independent period and cultured  for 7 days with pools of GAD65 overlapping
      peptides in the presence of IL-2. Cytokine secretion profiles of peptide-reactive
      T-cells were analyzed after a short-term restimulation with the same peptides by
      a multiplex bead-based cytokine assay and by an intracytoplasmic cytokine
      detection  assay. Robust GAD65-specific CD4(+) and CD8(+) T-cell responses were
      detected in patients who eventually developed chronic graft dysfunction. Multiple
      GAD65 peptides were found to induce specific T-cell responses in these patients,
      indicating that the repertoire of GAD65-specific  T-cells was broad. Furthermore,
      GAD65-specific CD4(+) T-cells were composed of heterogeneous populations, which
      differentially expressed cytokines including IFN-gamma and type 2 cytokines, but
      not IL-10. In contrast, patients who showed only marginal GAD65-specific T-cell
      responses  maintained substantially longer graft survival and insulin
      independence. In conclusion, our study suggests that the emergence of islet
      specific T-cells precedes the development of chronic graft dysfunction in islet
      transplanted patients. Thus, our observations support the hypothesis that these 
      islet-specific T-cells contribute to the development of chronic islet graft
      dysfunction.

PMID- 22963905
TI  - Pre-existing diabetes mellitus and adverse pregnancy outcomes.
AB  - BACKGROUND: Pregnancies complicated by pre-existing diabetes mellitus (PDM) are
      associated with a high rate of adverse outcomes, including an increased
      miscarriage rate, preterm delivery, preeclampsia, perinatal mortality and
      congenital malformations; compared to the background population. The objectives
      of this study are to determine the prevalence of PDM and to investigate the
      maternal and the neonatal outcomes of women with PDM. METHODS: This is a
      retrospective cohort study for women who delivered in King Khalid University
      Hospital (KKUH) during the period of January 1st to the 31st of December 2008.
      The pregnancy outcomes of the women with PDM were compared to the outcomes of all
      non-diabetic women who delivered during the same study period. RESULTS: A total
      of 3157 deliveries met the inclusion criteria. Out of the study population 116
      (3.7%) women had PDM. There were 66 (57%) women with type 1 diabetes mellitus
      (T1DM) and 50 (43%) women with type 2 diabetes mellitus (T2DM). Compared to non
      diabetic women those with PDM were significantly older, of higher parity, and
      they had more previous miscarriages. Women with PDM were more likely to be
      delivered by emergency cesarean section (C/S), OR 2.67, 95% confidence intervals
      (CI) (1.63-4.32), P < 0.001, or elective C/S, OR 6.73, 95% CI (3.99-11.31), P <
      0.001. The neonates of the mothers with PDM were significantly heavier, P <
      0.001; and more frequently macrosomic; OR 3.97, 95% CI (2.03-7.65), P = 0.002.
      They more frequently have APGAR scores <7 in 5 minutes, OR 2.61, 95% CI (0.89
      7.05), P 0.057 and more likely to be delivered at <37 gestation weeks, OR 2.24,
      95% CI (1.37- 3.67), P 0.003. The stillbirth rate was 2.6 times more among the
      women with PDM; however the difference did not reach statistical significance, P
      0.084. CONCLUSION: PDM is associated with increased risk for C/S delivery,
      macrosomia, stillbirth, preterm delivery and low APGAR scores at 5 min.

PMID- 22963906
TI  - Use of novel species-specific PCR primers targeted to DNA gyrase subunit B (gyrB)
      gene for species identification of the Cronobacter sakazakii and Cronobacter
      dublinensis.
AB  - Cronobacter sakazakii and its phylogenetically closest species are considered to
      be an opportunistic pathogens associated with food-borne disease in neonates and
      infants. Neither phenotypic nor genotypic (16S ribosomal DNA sequence analysis)
      techniques can provide sufficient resolutions for accurately and rapidly
      identification of these species. The objective of this study was to develop
      species-specific PCR based on the gyrB gene sequence for direct species
      identification of the C. sakazakii and Cronobacter dublinensis within the C.
      sakazakii group. Two pair of species-specific primers were designed and used to
      specifically identify C. sakazakii and C. dublinensis, but none of the other C.
      sakazakii group strains. Our data indicate that the novel species-specific
      primers could be used to rapidly and accurately identify the species of C.
      sakazakii and C. dublinensis from C. sakazakii group by the PCR based assays.

PMID- 22963907
TI  - An introduction to the calculation of valence EELS: quantum mechanical methods
      for bulk solids.
AB  - The low-loss region of the electron energy-loss spectrum, the valence EELS,
      provides information about the electronic structure and optical properties of
      materials. For bulk materials the spectral intensity can be directly connected to
      the complex dielectric function. Ab initio quantum mechanical calculations have
      an important role to play in the interpretation of the fine spectral detail and
      how this can be connected to the material properties. This paper provides an
      overview of theoretical background to the calculation of valence EELS in bulk
      solids and gives specific details on how to run such calculations using the
      WIEN2k code. The comparison of Au and AuAl(2) illustrates how in metals such
      calculations are successful in reproducing the main spectral details and can be
      used to understand the origin of the different colours of these two metals.

PMID- 22963908
TI  - Hepatitis C virus prevalence in The Netherlands: migrants account for most
      infections.
AB  - A population-based anti-hepatitis C virus (HCV) prevalence is important for
      surveillance purposes and it provides insight into the burden of disease. The
      outcomes of recent studies in the general Dutch population as well as recent HCV
      data from specific risk groups including migrants, men who have sex with men
      (MSM) and injecting drug users (IDUs), were implemented in a modified version of
      the Workbook Method (a spreadsheet originally designed for HIV estimations), to
      estimate Dutch HCV seroprevalence. The estimated national seroprevalence of HCV
      was 0.22% (min 0.07%, max 0.37%), corresponding to 28 100 (min n = 9600, max n =
      48 000) HCV-infected individuals in The Netherlands. Of these, first-generation
      migrants from HCV-endemic countries (HCV prevalence >=2%) accounted for the
      largest HCV-infected group, followed by IDUs and HIV-positive MSM.

PMID- 22963909
TI  - Non-alcoholic fatty liver disease is associated with high prevalence of gastro
      oesophageal reflux symptoms.
AB  - BACKGROUND: Gastro-oesophageal reflux symptoms are usually reported by patients
      with obesity and metabolic syndrome. Aim of this study was to assess the
      prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in
      subjects with non-alcoholic fatty liver disease. METHODS: Cross-sectional, case
      control study of 185 consecutive patients with non-alcoholic fatty liver disease
      and an age- and sex-matched control group of 112 healthy volunteers. Participants
      were interviewed with the aid of a previously validated questionnaire to assess
      lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios
      were determined before and after adjustment for body mass index, increased waist
      circumference, physical activity, metabolic syndrome and proton pump inhibitors
      and/or antiacid medication. RESULTS: The prevalence of heartburn and/or
      regurgitation and of at least one of gastro-oesophageal reflux symptoms was
      significantly higher in the non-alcoholic fatty liver disease group. Non
      alcoholic fatty liver disease subjects were associated to higher prevalence of
      heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04),
      regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48)
      and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59)
      and had higher prevalence of at least one GER symptom (adjusted odds ratios:
      3.34, 95% confidence intervals: 1.76-6.36). CONCLUSION: Non-alcoholic fatty liver
      disease is associated with a higher prevalence of gastro-oesophageal reflux
      symptoms.

PMID- 22963910
TI  - Enzyme replacement therapy in patients with Fabry disease: state of the art and
      review of the literature.
AB  - Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from
      the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent
      accumulation of globotrioasoyl ceramide in cells and tissues of the body,
      resulting in a multi-system pathology including end organ failure. In the
      classical phenotype, cardiac failure, renal failure and stroke result in a
      reduced median life expectancy. The current causal treatment for Fabry disease is
      the enzyme replacement therapy (ERT): two different products, Replagal
      (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially
      available in Europe for almost 10 years and they are both indicated for long-term
      treatment. In fact, clinical trials, observational studies and registry data have
      provided many evidences for safety and efficacy of ERT in improving symptoms of
      pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index,
      glomerular filtration rate and quality of life. Few data are available on
      comparison of the two treatments and on the clinical course of the disease. This
      article reviews the published evidence for clinical efficacy of the two available
      enzyme preparations.

PMID- 22963912
TI  - Analysis of the electrosensory pyramidal cell bursting model for weakly electric
      fish: model prediction under low levels of dendritic potassium conductance.
AB  - Pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric
      fish produce burst discharge. A Hodgkin-Huxley-type model, called ghostburster,
      consisting of two compartments (soma and dendrite) reproduces ELL pyramidal cell
      bursting observed in vitro. A previous study analyzed the ghostburster by
      treating Is and gDr,d as bifurcation parameters (Is: current injected into the
      somatic compartment and gDr,d: maximal conductance of the delayed rectifying
      potassium current in the dendritic compartment) and indicated that when both Is
      and gDr,d are set at particular values, the ghostburster shows a codimension-two
      bifurcation at which both saddle-node bifurcation of fixed points and saddle-node
      bifurcation of limit cycles occur simultaneously. In the present study, the
      ghostburster was investigated to clarify the bursting that occurred at gDr,d
      values smaller than that at the codimension-two bifurcation. Based on the number
      of spikes per burst, various burst patterns were observed depending on the (Is,
      gDr,d) values. Depending on the (Is, gDr,d) values, the burst trajectory in a
      phase space of the ghostburster showed either a high or a low degree of
      periodicity. Compared to the previous study, the present findings contribute to a
      more detailed understanding of ghostburster bursting.

PMID- 22963911
TI  - Ectodermal markers of early developmental impairment in very preterm individuals.
AB  - Individuals born very preterm (before 33 weeks' gestation; VPT) are at risk of
      life-long, neurological impairments, behavioural and other health problems. It is
      not clear whether these neurodevelomental abnormalities originate prenatally,
      postnatally or a combination of both. Dermatoglyphics are stable ectodermal
      markers of neurodevelopmental disruption in the early prenatal period, as it has
      previously been reported in neuropsychiatric disorders such as schizophrenia or
      bipolar disorder. We have analyzed the dermatoglyphic variable total a-b ridge
      count (TABRC), which is a sensitive marker of ectodermal disruption during the
      first 24 weeks of foetal development, in 142 very preterm (VPT) individuals and
      64 term born young adults. The VPT group showed significantly lower TABRC than
      the term group, especially those individuals presenting very low birth weight
      (VLBW), considered a proxy for more extreme prenatal stress, as shown by a two
      way Anova analysis. These individuals, at risk of brain abnormalities and
      behavioural impairments, may have undergone disturbances before preterm birth
      occurs and prior to the 24th week of gestation. Our results support that
      dermatoglyphics represent a suitable marker to detect ectodermal alterations
      which have occurred very early in the course of development, and point out the
      vulnerability of the immature brain during the first half of gestation which may
      have adverse health consequences later in life.

PMID- 22963913
TI  - Ductular reaction at the early terms of common bile duct ligation in the rats.
AB  - Ductular reaction (DR) in bile duct ligated rats generally appears from 2nd day
      after biliary obstruction (BO). However, we show that increased amount of
      ductular profiles is evident already in 6 hours after BDL. The study aims to
      explain the origin of such an early DR in response to BO. Male Lewis rats were
      subjected to common bile duct ligation (CBDL) for 3, 6, 12 and 24 hours and sham
      operation. Liver samples were studied histologically, immunohistochemically
      (Ki67, pan-Cytokeratin /AE1 + AE3/ and OV-6) and by immunoblotting analyses. It
      appeared that number of ductular profiles increase in time-related manner after
      BO. These ductular profiles are formed by biliary epitheliocyte-like cells; No
      mitotic activity was revealed. Part of hepatocytes reveals pan-Cytokeratin
      positivity on 12 and 24 hours after BO. Total cytokeratins content at 24 hours
      after CBDL was 37% higher in comparison with control data. The significant
      increase was observed for the cytokeratins with molecular weights: 61, 56 and 40
      KDa. Thus, early DR after BDL is mediated by widening of the existed finest
      biliary ramifications and is not associated with proliferation activities. This
      DR is accompanied by differentiation of hepatocytes toward bile duct-like cells.

PMID- 22963914
TI  - Morphology of dry-resistant eggs in parthenogenetic Heterocypris incongruens
      (Ramdohr, 1808) (Ostracoda, Crustacea).
AB  - It has been known that many organisms evolved to survive in temporary or
      ephemeral inland waters. Many of them have dry-resistant eggs against
      desiccation. The structural feature of egg shell is important because only this
      will ensure to survive the dry period. Structural features of egg shell in the
      parthenogenetic Heterocypris incongruens (Ramdohr, 1808) was investigated by
      scanning electron microscope. Results showed that egg shell structure consists of
      two distinct layers; an outer layer with holes or alveoli and an inner layer
      consisting of two dense sublayers. Also, structural similarities in egg-shell of
      H. incongruens and some other crustaceans which combat desiccation problem will
      be discussed.

PMID- 22963915
TI  - Antimetabolic effect of phytohemagglutinin to the grain aphid Sitobion avenae
      fabricius.
AB  - The insecticidal activity of plant lectins against a wide range of insect species
      have been intensively studied. Understanding the mechanism of the toxicity of
      lectins is one of the studied aspects. In the present research, the first step
      was determine the effect of phytohemagglutinin (PHA) on the development,
      fecundity and mortality of grain aphid. Next, the effect of PHA lectin on the
      activity of such enzymes as: alpha- and beta-glucosidases, alkaline (AkP) and
      acid (AcP) phosphatases, aminopeptidase N and cathepsin L involved in the
      metabolism of sugar, phosphorus and proteins of an adult apterae aphids was
      investigated. The PHA lectin added into the liquid diet increased the pre
      reproductive period, mortality of Sitobion avenae, the time of generation
      development and decreased its fecundity and the intrinsic rate of natural
      increase. In addition, activity of alpha-glucosidase, alkaline phosphatase and
      aminopeptidase N of adult apterae exposed to PHA were reduced. The results
      indicate that the insecticidal activity of PHA on S. avenae may involve changes
      in activity of the enzymes in the midgut and it may be part of its toxicity.

PMID- 22963916
TI  - An antidote for imazalil-induced genotoxicity in vitro: the lichen, Dermatocarpon
      intestiniforme (Korber) Hasse.
AB  - Imazalil (IMA), a commonly used fungicide in both agricultural and clinical
      domains, is suspected to produce serious toxic effects in vertebrates. In recent
      years, a number of studies have suggested that lichens might be easily accessible
      sources of natural drugs that could be used as a possible food supplement.
      Extensive research is being performed to explore the importance of lichen
      species, which are known to contain a variety of pharmacological active
      compounds. In this context, the antigenotoxic effect of aqueous Dermatocarpon
      intestiniforme (Korber) Hasse. extract (DIE) was studied against the genotoxic
      damage induced by IMA on cultured human lymphocytes (n = 6) using chromosomal
      aberration (CA) and micronucleus (MN) as cytogenetic endpoints. Human peripheral
      lymphocytes were treated in vitro with varying concentrations of DIE (0, 25, 50
      and 100 MUg/ml), tested in combination with IMA (336 MUg/ml). DIE alone were not
      genotoxic and when combined with IMA treatment, it reduced the frequency of CAs
      and the rate of MNs. A clear dose-dependent decrease in the genotoxic damage of
      IMA was observed, suggesting a genoprotective role of DIE. The results of the
      present study suggest that this plant extract per se does not have a genotoxic
      potential, but can alleviate the genotoxicity of IMA on cultured human
      lymphocytes. In conclusion our findings may have an important application for the
      protection of cultured human lymphocyte from the genetic damage and side effects
      induced by medical and agricultural chemicals hazardous for people.

PMID- 22963917
TI  - Effects of aqueous extracts of Paeonia decomposita seeds on germination and some
      metabolic activities associated with growth of wheat seedlings.
AB  - Paeonia decomposita is a perennial deciduous shrub with great ornamental and
      medicinal values. Unfortunately, the distribution region, population size and
      individual numbers of P. decomposita rapidly decrease in the wild. It is a
      particularly rare, highly endangered, protective plant endemic to Southwest
      China. To understand the causes of seed dormancy of P. decomposita, the effects
      of aqueous extracts of the seed coat, endosperm of P. decomposita on germination,
      seedling growth and amylases activities of wheat seeds were examined in this
      paper. The results showed that the seed, especially the endosperm tissue of P.
      decomposita contained substances that strongly suppressed seed germination. The
      crude extract of endosperm of P. decomposita, which significantly reduced the
      activities of alpha and beta-amylase, showed a more significant inhibition than
      that of seed coat at the same dose. It was concluded that the presence of
      inhibitory substances in seed, especially in endosperm tissue, seem to be
      responsible for P. decomposita seed dormancy.

PMID- 22963918
TI  - The optimization of regeneration tissue culture system of three chilli peppers
      cultivars based on the uniform design and the mathematical model equation.
AB  - Using uniform random design optimization and the mathematical model equation we
      optimized the regeneration tissue culture system of the chilli pepper. An
      efficient and detailed plant reproducible protocol in vitro has been established
      using different explants and induction media for three chilli pepper cultivars.
      The result displayed that the seedlings at the curved hypocotyl stage were the
      best choice to prepare for explants, the genotype of explants affected shoot buds
      induction frequency and number of shoot buds per explant, and the cotyledon
      explant was more responsive than hypocotyl explant. The optimal media for maximum
      shoot initiation and regeneration and the optimal elongation medium were
      obtained. For Capsicum annuum var. annuum (cv. Xinsu), Capsicum annuum var.
      annuum (cv. Neimengchifeng) and Capsicum frutescens (cv. Xingfu), the induction
      rates were 99.17%, 97.50 and 96.11%, respectively; the elongation rates of shoot
      buds were 86.67%, 85.19% and 82.96%, respectively. The MS medium with 0.57 MUM
      IAA and 0.69 MUM NAA is the best choice for root induction. The frequency of
      their root emergence was 95.00-98.33%. Regenerated chilli peppers were
      successfully acclimatized and cultivated with 100% survival. This work will help
      to improve multiplication process and the genotype of chilli pepper, and may have
      commercial impact.

PMID- 22963919
TI  - Thermodynamic and kinetic processes during the unfolding of BSA in the presence
      of the mycotoxin patulin.
AB  - The effects of the mycotoxin patulin on the thermodynamics and kinetics of the
      transition of bovine serum albumin (BSA) in aqueous solution were studied by
      Differential Scanning Calorimetry and Photoluminescence methods. Results show
      that in the presence of patulin, the free enthalpy change during the transition
      of BSA was decreased by an average of ~ 46 kJ/mol, the free energy change was
      decreased by ~ 4 kJ/mol, and the activation energy fell from ~ 1546 to ~ 840
      kJ/mol. These results indicate that the bioactivity of patulin is based on the
      kinetic rather than on the thermodynamic properties of the transition. This is
      the first evidence of the direct interaction of patulin with the free thiol
      containing BSA, a process which could contribute to the adverse cyto- and
      genotoxic effects induced by patulin.

PMID- 22963920
TI  - fur (-) mutation increases the survival time of Escherichia coli under
      photooxidative stress in aquatic environments.
AB  - We investigated the survival of the wild type Escherichia coli (QC771) and fur-
      mutant strain (QC1732) under photooxidative stress in different water sources.
      The survival of fur- mutant and wild type E. coli was seen as a significant
      decrease in the visible light samples in the presence of methylene blue (MB). The
      fur-E. coli strain lived longer than the wild type E. coli strain on exposure to
      MB and visible light, which generates singlet oxygen, in both lake water (48-h)
      and pure water (16-h). It is interesting to note that the survival of both wild
      type and the fur- mutant strain was more protected at 24  degrees C than at other
      temperatures. The Fur protein does not have any relation to the entry of E. coli
      into the viable but nonculturable state (VBNC) under photooxidative stress. This
      is the first study which shows that fur- mutation increases the resistance of E.
      coli to photooxidative stress in aquatic environments, and the Fur protein does
      not have any relation to the entry of E. coli into the VBNC state.

PMID- 22963921
TI  - A randomized controlled trial to improve health among women receiving welfare in
      the US: the relationship between employment outcomes and the economic recession.
AB  - The high prevalence of health conditions among U.S. women receiving Temporary
      Assistance for Needy Families (TANF, or 'welfare') impedes the ability of many in
      this group to move from 'welfare-to-work', and the economic recession has likely
      exacerbated this problem. Despite this, few interventions have been developed to
      improve employment outcomes by addressing the health needs of women receiving
      TANF, and little is known about the impact of economic downturns on the
      employment trajectory of this group. Using data from a recent randomized
      controlled trial (RCT) that tested the efficacy of a public health nursing (PHN)
      intervention to address the chronic health condition needs of 432 American women
      receiving TANF, we examine the effect of the intervention and of recession
      exposure on employment. We further explore whether intervention effects were
      modified by select sociodemographic and health characteristics. Both marginal and
      more robust intervention effects were noted for employment-entry outcomes (any
      employment, p = 0.05 and time-to-employment, p = 0.01). There were significant
      effects for recession exposure on employment-entry (any employment, p = 0.002 and
      time-to-employment, p < 0.001). Neither the intervention nor recession exposure
      influenced longer-term employment outcomes (employment rate or maximum continuous
      employment). Intervention effects were not modified by age, education, prior TANF
      receipt, functional status, or recession exposure, suggesting the intervention
      was equally effective in improving employment-entry across a fairly heterogeneous
      group both before and after the recession onset. These findings advance our
      understanding of the health and employment dynamics among this group of
      disadvantaged women under variable macroeconomic conditions, and have
      implications for guiding health and TANF-related policy.

PMID- 22963922
TI  - What counts and how to count it: physicians' constructions of evidence in a
      disinvestment context.
AB  - Internationally, there is an increasing focus on quality and sustainability
      measures oriented to reducing inefficiencies in health provision. The use of
      assisted reproductive technologies (ART) for older women represents a case study
      in this area. This paper analyses the constructions of evidence brought to bear
      by ART physicians in the context of deliberative stakeholder engagements (held
      2010) around options for restricting public subsidy of ART in Australia.
      Physicians participated in two deliberative engagements during which they were
      presented with results of a systematic review of ART effectiveness, as well as
      ethical and cost analyses. These sessions were part of a broader research program
      of engagements held with policymakers, community members and consumers.
      Physicians deliberated around the data presented with a view to formulating an
      informed contribution to policy. The ensuing discussions were transcribed and
      subject to discourse analysis. Physicians questioned the evidence presented on
      the grounds of 'currency', 'proximity', 'selectivity' and 'bias'. We outline
      physicians' accounts of what should count as evidence informing ART policy, and
      how this evidence should be counted. These accounts reflect implicit decisions
      around both the inclusion of evidence (selection) and the status it is accorded
      (evaluation). Our analysis suggests that participatory policy processes do not
      represent the simple task of assessing the quality/effectiveness of a given
      technology against self-evident criteria. Rather, these processes involve the
      negotiation of different orders of evidence (empirical, contextual and
      anecdotal), indicating a need for higher-level discussion around 'what counts and
      how to count it' when making disinvestment decisions.

PMID- 22963923
TI  - Vaccine innovation, translational research and the management of knowledge
      accumulation.
AB  - What does it take to translate research into socially beneficial technologies
      like vaccines? Current policy that focuses on expanding research or strengthening
      incentives overlooks how the supply and demand of innovation is mediated by
      problem-solving processes that generate knowledge which is often fragmented and
      only locally valid. This paper details some of the conditions that allow
      fragmented, local knowledge to accumulate through a series of structured steps
      from the artificial simplicity of the laboratory to the complexity of real world
      application. Poliomyelitis is used as an illustrative case to highlight the
      importance of experimental animal models and the extent of co-ordination that can
      be required if they are missing. Implications for the governance and management
      of current attempts to produce vaccines for HIV, TB and Malaria are discussed.

PMID- 22963924
TI  - Valproate causes reduction of the excitatory amino acid aspartate in nerve
      terminals.
AB  - Valproate is well established in the treatment of epilepsy and psychiatric
      disorders, yet the main mechanism of action remains to be determined. Here we
      show that valproate may reduce neurotransmission of the excitatory amino acid,
      aspartate. By electron microscopic immunogold cytochemistry we demonstrate a 63
      68% reduction in the level of aspartate in excitatory nerve terminals at 30 min
      after an acute dose of valproate. The level of glutamate in the same terminals
      was unchanged by valproate treatment. In inhibitory terminals, valproate caused a
      65% decrease in the aspartate level, whereas the GABA level was not significantly
      changed. In summary, the present study shows that valproate reduces the nerve
      terminal content of the excitatory neurotransmitter aspartate. This points to a
      new mechanism of action for valproate: reduced neuronal excitation through
      reduced aspartergic neurotransmission.

PMID- 22963925
TI  - NEDD9 rs760678 polymorphism and the risk of Alzheimer's disease: a meta-analysis.
AB  - The NEDD9 rs760678 polymorphism has been extensively investigated for association
      to Alzheimer's disease (AD), however, results of different studies have been
      inconsistent. The objective of this study is to assess the relationship of NEDD9
      rs760678 polymorphism and AD risk by using meta-analysis. Systematic searches of
      electronic databases Pubmed and Embase, as well as hand searching of the
      references of identified articles were performed. Statistical analyses were
      performed using software Revman 4.2 and STATA 11.0. A total of 4436 cases and
      4420 controls in 11 case-control studies were included. The results indicated
      that the homozygote GG had a 13% decreased risk of AD, when compared with the C
      allele carriers (CC+CG) (OR=0.87, 95%CI=0.77-0.99, P=0.04 for GG vs. CG+CC). In
      the subgroup analysis by ethnicity, significant decreased risk was associated
      with homozygote GG or G allele carriers in Caucasians (OR=0.84, 95%CI=0.74-0.96,
      P=0.008 for GG vs. CG+CC; OR=0.79, 95%CI=0.69-0.91, P=0.001 for GG vs. CC;
      OR=0.90, 95%CI=0.84-0.96, P=0.002 for G vs. C), but not in Asians. This meta
      analysis suggests that the GG genotype of NEDD9 rs760678 polymorphism would be a
      protective factor for AD in Caucasians but not in Asians. To further evaluate the
      effect of gene-gene and gene-environmental interactions between NEDD9 rs760678
      polymorphism and the risk of AD, more studies with larger number of subjects are
      required.

PMID- 22963926
TI  - Introduction to special issue on phosphoproteomics.

PMID- 22963927
TI  - Oral and extra-oral taste perception.
AB  - Of the five basic taste qualities, the molecular mechanisms underlying sweet,
      bitter, and umami (savory) taste perception have been extensively elucidated,
      including the taste receptors and downstream signal transduction molecules.
      Recent studies have revealed that these taste-related molecules play important
      roles not only in the oral cavity but also in a variety of tissues including the
      respiratory tract, stomach, intestines, pancreas, liver, kidney, testes, and
      brain. This review covers the current knowledge regarding the physiological roles
      of taste-related molecules in the oral and extra-oral tissues.

PMID- 22963928
TI  - Effects of altering motivation for food in rats trained with food reinforcement
      to discriminate between d-amphetamine and saline injections.
AB  - Previous studies have shown that altering motivation typically affects stimulus
      generalization in animals trained to discriminate exteroceptive stimuli, but few
      studies have evaluated the effects of manipulating motivation on drug stimuli. In
      the few published studies, motivation levels were manipulated by arranging
      different feeding conditions prior to stimulus generalization tests with rats
      trained to discriminate morphine from vehicle and in pigeons trained to
      discriminate phencyclidine or pentobarbital from vehicle. In the present study,
      rats maintained at 80% of free-feeding weights were trained to discriminate
      between injections of 1.0mg/kg d-amphetamine and saline in a two-lever food
      reinforced operant procedure. Generalization tests were then conducted with a
      range of d-amphetamine doses (0, 0.03, 0.1, and 0.3, 1.0mg/kg) when the rats were
      not fed before experimental sessions (high motivation) and when they were pre-fed
      1g of food (moderate motivation) or their daily ration of food (low motivation)
      1h before test sessions. Changing the motivation level significantly affected
      response rate and latency to the first response in generalizations tests, but did
      not significantly affect mean percentage of drug-appropriate responding (a
      continuous measure) or percentage of animals that selected the drug-appropriate
      lever (a quantal measure). The present findings indicate that manipulating
      motivation for food minimally impacts d-amphetamine discrimination, however, the
      range of conditions used to examine the effects of motivating operations on
      stimulus control by d-amphetamine drugs and other drugs is limited and the topic
      may warrant further investigation.

PMID- 22963929
TI  - Age-dependent changes in the susceptibility to thiopental anesthesia in mice:
      analysis of the relationship to the functional expression of GABA transporter.
AB  - The potency of anesthetics changes during development, probably due not only to
      pharmacokinetic factors such as differential distribution and/or metabolism, but
      also to pharmacodynamic factors such as changes to the GABAergic system in the
      brain. To explore the latter mechanism, we focused on the GABA transporter (GAT),
      the uptake system for GABA, which participates in the synaptic clearance of GABA.
      Thiopental-induced anesthesia, as assessed by the onset and duration of loss of
      the righting reflex, was more pronounced in 3-week-old mice than in 7-week-old
      mice. Both NO-711 and SKF89976A, selective GAT-1 inhibitors, significantly
      enhanced the anesthesia in the 7-week-old but not in the 3-week-old mice. In
      synaptosomes prepared from the cerebral cortex, the kinetics of GABA transport
      was similar between the two age groups, as assessed by [(3)H]GABA uptake assay.
      In addition, expression of GAT mRNA was similar between the two age groups, as
      assessed by quantitative RT-PCR. Thiopental reduced [(3)H]GABA uptake only at
      high concentrations in a similar manner at both ages. Conversely, the ability of
      SKF89976A to inhibit [(3)H]GABA uptake was greater in the 7-week-old mice than in
      the 3-week-old mice. Based on these results, GAT seems unlikely to contribute to
      the greater susceptibility to thiopental anesthesia in 3-week-old mice, while the
      increased ability of GABA uptake inhibitors to enhance thiopental-induced
      anesthesia in 7-week-old mice is at least partly due to higher sensitivity of GAT
      to the inhibitors.

PMID- 22963931
TI  - Comparative energetics of mammalian locomotion: humans are not different.
AB  - Debates about the evolution of human bipedality sometimes include discussion on
      the energy costs of terrestrial locomotion of extinct and extant hominins.
      However, comparative analyses of hominin transport costs conducted to date have
      been limited and potentially misinforming, in part because they fail to consider
      phylogenetic history. In the present study, we compare the measured costs of
      pedestrian locomotion in humans and the estimated costs for Australopithecus
      afarensis (an early bipedal hominin), to a database of locomotory costs for
      mammals. Using data for 81 species of mammal, we demonstrate significant
      phylogenetic signal in both log-transformed body mass (logMass) and log
      transformed net cost of transport (logNCOT), but no phylogenetic signal in
      residuals of the relationship between logNCOT and logMass. We then used this
      relationship to generate a prediction line for NCOT based on body mass, and
      compared this prediction with published measured data for NCOT of running and
      walking in humans, and estimated NCOT of walking in A. afarensis. The cost of
      human walking was 25% lower than predicted, while the cost of running was 27%
      higher. The cost of A. afarensis walking was 32% lower than predicted. However,
      all of these data points fall within the 95% prediction interval for mammals,
      indicating that they are not significantly lower or higher than predicted for
      other mammals of similar mass. Moreover, the difference between humans and our
      closest living relative the common chimpanzee is comparable to differences
      between other similarly closely related species. We therefore conclude that there
      is no evidence from metabolic data that humans, or A. afarensis, have/had a
      reduced energy cost of pedestrian locomotion compared to other mammals in
      general.

PMID- 22963932
TI  - A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and
      tolerability of 5 mg vortioxetine in adults with major depressive disorder.
AB  - Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development
      for the treatment of major depressive disorder (MDD). The current study evaluated
      the efficacy and tolerability of 5 mg vortioxetine compared to placebo after 6 wk
      of treatment in adults with MDD in an out-patient setting. Adults aged 18-75 yr,
      with a diagnosis of MDD and a baseline Montgomery-Asberg Depression Rating Scale
      (MADRS) total score >=30, were randomized to receive either 5 mg vortioxetine or
      placebo over 6 wk, followed by a 2-wk medication-free discontinuation period. The
      primary efficacy measure was change from baseline in Hamilton Rating Scale for
      Depression (HAMD)-24 total score at week 6 compared to placebo. Additional
      measures included response and remission rates, Clinical Global Impression Scale 
      Improvement scores, HAMD-24 total score in subjects with baseline Hamilton
      Anxiety Scale (HAMA) >19 and MADRS-S total score. Adverse events (AEs) were
      assessed throughout the study. A total of 600 adults were randomized. There were
      no significant differences in efficacy measures between subjects in the 5 mg
      vortioxetine and placebo groups at week 6. HAMD-24 total score in subjects with
      baseline HAMA >19 in the 5 mg vortioxetine group was improved at weeks 3-6
      compared to the placebo group (nominal p value <0.05). The most common AEs for
      the vortioxetine and placebo groups were nausea (19.1 and 9.4%), headache (17.1
      and 15.1%) and diarrhoea (11.4 and 7.0%), respectively. In this study of adults
      with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing
      depression symptoms after 6 wk of treatment.

PMID- 22963930
TI  - Custom genotyping for substance addiction susceptibility genes in Jordanians of
      Arab descent.
AB  - BACKGROUND: Both environmental and genetic factors contribute to individual
      susceptibility to initiation of substance use and vulnerability to addiction.
      Determining genetic risk factors can make an important contribution to
      understanding the processes leading to addiction. In order to identify gene(s)
      and mechanisms associated with substance addiction, a custom platform array
      search for a genetic association in a case/control of homogenous Jordanian Arab
      population was undertaken. Patients meeting the DSM-VI criteria for substance
      dependence (n = 220) and entering eight week treatment program at two Jordanian
      Drug Rehabilitation Centres were genotyped. In addition, 240 healthy controls
      were also genotyped. The sequenom MassARRAY system (iPLEX GOLD) was used to
      genotype 49 single nucleotide polymorphisms (SNPs) within 8 genes (DRD1, DRD2,
      DRD3, DRD4, DRD5, BDNF, SLC6A3 and COMT). RESULTS: This study revealed six new
      associations involving SNPs within DRD2 gene on chromosome 11. These six SNPs
      within the DRD2 were found to be most strongly associated with substance
      addiction in the Jordanian Arabic sample. The strongest statistical evidence for
      these new association signals were from rs1799732 in the C/-C promoter and
      rs1125394 in A/G intron 1 regions of DRD2, with the overall estimate of effects
      returning an odds ratio of 3.37 (chi2 (2, N = 460) = 21, p-value = 0.000026) and
      1.78 (chi2 (2, N = 460) = 8, p-value = 0.001), respectively. It has been
      suggested that DRD2, dopamine receptor D2, plays an important role in dopamine
      secretion and the signal pathways of dopaminergic reward and drug addiction.
      CONCLUSION: This study is the first to show a genetic link to substance addiction
      in a Jordanian population of Arab descent. These findings may contribute to our
      understanding of drug addiction mechanisms in Middle Eastern populations and how
      to manage or dictate therapy for individuals. Comparative analysis with different
      ethnic groups could assist further improving our understanding of these
      mechanisms.

PMID- 22963933
TI  - Prostaglandins, not the leukotrienes, regulate Cl(-)/HCO(3)(-) exchange (DRA,
      SLC26A3) in villus cells in the chronically inflamed rabbit ileum.
AB  - Previously studies have demonstrated that Cl(-)/HCO(3)(-) exchange was inhibited
      during chronic intestinal inflammation secondary to decrease in the affinity of
      the exchanger for Cl(-) rather than the number of transporters. Arachidonic acid
      metabolites (AAM) are elevated in the mucosa of the chronically inflamed small
      intestine. However, their role in the alteration of Cl(-)/HCO(3)(-) during
      chronic enteritis was unknown. Inhibition of AAM formation with arachidonyl
      trifluoro methylketone (ATMK) in chronically inflamed rabbit intestine reversed
      the diminished Cl(-)/HCO(3)(-) exchange activity. Kinetics studies showed that
      the reversal was secondary to restoration of the altered affinity of transporter.
      Downstream regulation of Cl(-)/HCO(3)(-) inhibition by AAM was determined to be
      by the cyclooxygenase pathway since only inhibition of cyclooxygenase with
      piroxicam treatment reversed the inhibited Cl(-)/HCO(3)(-) exchange. Further, DRA
      was shown to be the primary Cl(-)/HCO(3)(-) exchanger in villus cells. Kinetics
      and molecular studies indicated that the mechanism of inhibition of Cl(-)/HCO(3)(
      ) exchange by cyclooxygenase pathway metabolites was secondary to diminished
      affinity of the transporter for Cl(-) without a change in DRA BBM expression.
      Thus our data indicated that cyclooxygenase pathway metabolites mediate the
      inhibition of DRA during chronic intestinal inflammation.

PMID- 22963934
TI  - Alcohol use and abuse among patients with multidrug-resistant tuberculosis in
      Botswana.
AB  - BACKGROUND: Data on alcohol abuse as a risk factor for the development of
      multidrug-resistant tuberculosis (MDR-TB) are scarce. OBJECTIVE: To describe the
      patterns of alcohol use in MDR-TB patients and to determine whether alcohol use
      is associated with the development of MDR-TB  in Botswana. METHODS: We compared
      the level of alcohol use among MDR-TB patients against three control groups: 1)
      non-MDR-TB patients, 2) human immunodeficiency virus (HIV) infected patients
      without a history of TB, and 3) the general population. Alcohol use and abuse was
      measured with  the Alcohol Use Disorders Identification Test 10 (AUDIT)
      questionnaire. RESULTS: Of a total national population of 164 MDR-TB cases, 114
      (70%) were interviewed. MDR-TB cases had a lifetime prevalence of alcohol use of
      35.1%, which was lower than that of all control groups (P <  0.001). MDR-TB cases
      had higher 1-month prevalence of alcohol dependence symptoms and a lower 1-year
      period prevalence of alcohol dependence symptoms (P < 0.01 and P = 0.01
      respectively). Among patients with TB, alcohol abuse was found to be a risk
      factor for the development  of MDR-TB. CONCLUSION: MDR-TB patients in Botswana
      have high rates of alcohol use and abuse. Among TB patients, alcohol abuse is
      associated with the diagnosis of MDR-TB, and could be an important modifiable
      factor.

PMID- 22963935
TI  - Humoral response of captive zebra sharks Stegostoma fasciatum to salivary gland
      proteins of the leech Branchellion torpedinis.
AB  - Parasitism by the marine leech Branchellion torpedinis is known to cause disease
      and mortality in captive elasmobranchs and is difficult to control when
      inadvertently introduced into public aquaria. Preliminary characterization of the
      salivary gland transcriptome of B. torpedinis has identified anticoagulants,
      proteases, and immunomodulators that may be secreted into host tissues to aid
      leech feeding. This retrospective study examined antigen-specific serum IgM
      responses in captive zebra sharks Stegostoma fasciatum to leech salivary gland
      extract. Antibody response was examined by ELISA and Western blot assays in 20
      serum samples from six zebra sharks, with a 5 year history of leech infection,
      and 18 serum samples from 8 captive bred zebra sharks, with no history of leech
      exposure. ELISA demonstrated significantly higher serum IgM titers to salivary
      gland extract in exposed zebra sharks compared to the non-exposed population. No
      obvious trends in antibody titers were appreciated in exposed zebra sharks over a
      four-year period. One-dimensional and two-dimensional Western blot assays
      revealed IgM targeted specific salivary gland proteins within the 40, 55, 70 and
      90 kD range. Antigenic proteins identified by liquid chromatography-tandem mass
      spectrometry and de novo peptide sequencing include a secreted disintegrin,
      metalloproteinase and thrombospondin motif containing protein (ADAMTS), tubulin,
      aldehyde dehydrogenase and two unknown proteins. Humoral immune responses to
      leech salivary gland proteins warrants further investigation as there may be
      options to exploit immune mechanisms to reduce parasite burdens in aquaria.

PMID- 22963936
TI  - Being sanguine about study design and multiple imputation.

PMID- 22963938
TI  - Incentives must be closely aligned to professional values.

PMID- 22963939
TI  - More on incentives.

PMID- 22963940
TI  - JCVI processes are at least as robust as those of scientific journals.

PMID- 22963941
TI  - JCVI processes should be more rigorous than those of scientific journals.

PMID- 22963942
TI  - Osteonecrosis of the jaw is becoming more common.

PMID- 22963943
TI  - Review overemphasises benefits and downplays serious harms.

PMID- 22963945
TI  - Caution is needed in extrapolating results of randomised controlled trial.

PMID- 22963946
TI  - Money well spent?

PMID- 22963947
TI  - Trial shows only that practice varies.

PMID- 22963949
TI  - Patient's fight to allow doctors to end his life is taken up by his widow.

PMID- 22963950
TI  - Democrats vow to strengthen Medicare and Medicaid and preserve women's health
      rights.

PMID- 22963951
TI  - [Intrasellar gangliocytoma associated with growth hormone-producing pituitary
      adenoma. Case report].
AB  - INTRODUCTION: Intrasellar gangliocytomas are uncommon entities which, unusually,
      may be found in association with hormone-releasing pituitary adenomas. CASE
      REPORT: The patient was a 49-year-old female who presented a sellar lesion with
      associated acromegaly. A trans-sphenoidal tumour was removed, with no medical
      improvement. Histopathological analysis revealed a gangliocytoma with an
      associated somatotroph adenoma. DISCUSSION: We found 85 cases of intrasellar
      gangliocytomas with associated hormone-releasing pituitary adenomas reported in
      the literature, with the following distribution: 50 growth hormone-releasing (GH)
      cases (59%), 15 mixed (GH and prolactin-releasing) cases (17%), 11 prolactin
      releasing cases (13%), 7 adrenocorticotropic hormone-releasing (ACTH) cases (8%)
      and 2 corticotropin hormone-releasing (CRH) cases (2%). CONCLUSIONS: Mixed
      gangliocytomas-adenomas are uncommon entities. Association with growth hormone
      releasing cases is more frequent and the most common presentation is among middle
      aged females. Diagnosis is histopathological. Identification of this entity is
      important because it may lead to a limitation in therapeutic response in
      incomplete resections.

PMID- 22963952
TI  - [Update in the diagnosis and treatment of malaria].
AB  - An increase in the cases of malaria in our country has been observed due to
      immigration, and adopted children. Malaria management requires an integrate
      approach, including prompt diagnoses and treatment to avoid the associated
      morbidity and mortality. In the last years, new recommendations have been
      introduced due to the appearance of new resistant areas. In this article we aim
      to provide a summary of the key recommendations following the main malaria
      guidelines (WHO and CDC).

PMID- 22963953
TI  - [De la Chapelle syndrome].

PMID- 22963954
TI  - Best practices for school nutrition efforts.

PMID- 22963955
TI  - SNEB 2012: creating community through synergy.

PMID- 22963957
TI  - Follicular bronchiolitis associated with common variable immunodeficiency.
AB  - Common variable immunodeficiency is one of the most frequent immunity
      alterations. The most common clinical presentation occurs with recurrent
      respiratory infections, from pneumonia to otitis, and may be associated with
      other diseases such as bronchiectasis or interstitial lung diseases. We report
      the case of a 28-year-old patient with frequent respiratory infections and
      nodular pulmonary infiltrates, who was diagnosed with common variable
      immunodeficiency and follicular bronchiolitis. In some cases, follicular
      bronchiolitis is associated with immunodeficiencies and should be included in a
      differential diagnosis with lymphoid nodular hyperplasia, lymphocytic
      interstitial pneumonia and low-grade BALT lymphoma.

PMID- 22963956
TI  - Associations among school characteristics and foodservice practices in a
      nationally representative sample of United States schools.
AB  - OBJECTIVE: Determine school characteristics associated with healthy/unhealthy
      food service offerings or healthy food preparation practices. DESIGN: Secondary
      analysis of cross-sectional data. SETTING: Nationally representative sample of
      public and private elementary, middle, and high schools. PARTICIPANTS: Data from
      the 2006 School Health Policies and Practices Study Food Service School
      Questionnaire, n = 526 for Healthy and Unhealthy Offerings analysis; n = 520 for
      Healthy Preparation analysis. MAIN OUTCOME MEASURES: Scores for healthy/unhealthy
      foodservice offerings and healthy food preparation practices. ANALYSIS:
      Multivariable regression to determine significant associations among school
      characteristics and offerings/preparation practices. RESULTS: Public schools and
      schools participating in the United States Department of Agriculture (USDA) Team
      Nutrition reported more healthy offerings and preparation than private or
      nonparticipating schools, respectively. Elementary schools reported fewer
      unhealthy offerings than middle or high schools; middle schools reported fewer
      unhealthy offerings than high schools. Schools requiring foodservice managers to
      have a college education reported more healthy preparation, whereas those
      requiring completion of a foodservice training program reported fewer unhealthy
      offerings and more healthy preparation than schools without these requirements.
      CONCLUSIONS AND IMPLICATIONS: Results suggest the school nutrition environment
      may be improved by requiring foodservice managers to hold a nutrition-related
      college degree and/or successfully pass a foodservice training program, and by
      participating in a school-based nutrition program, such as USDA Team Nutrition.

PMID- 22963958
TI  - [Cutaneous leishmaniasis: can the infective agent be determined on clinical
      grounds alone?].

PMID- 22963959
TI  - [Treatment of hookworm-related cutaneous larva migrans: albendazole or
      ivermectin?].

PMID- 22963960
TI  - [The value of biopsy in the diagnosis of penile dermatoses].
AB  - BACKGROUND: Penile biopsy can be useful to establish an accurate diagnosis when
      managing male genital dermatoses. We investigated the value of genital biopsy by
      comparing suspected clinical diagnosis with final histologic diagnosis. PATIENTS
      AND METHOD: We retrospectively examined the clinical file of men with genital
      dermatoses undergoing genital biopsy. We collected details of age, biopsy site,
      suspected diagnosis after clinical examination and histologic diagnosis. RESULTS:
      One hundred and thirty-eight male patients were enrolled in the study. Their mean
      age was 52 years. Most biopsies (41%) were performed on the glans. Microscopic
      examination failed to rule out a diagnosis in 14.5% of the cases. It confirmed
      the clinically suspected diagnosis in 29.7% of cases and ruled out a particular
      diagnosis from among several clinical hypotheses in 26.8% of cases. The
      histological diagnosis had not been suspected in 18.1% of cases. DISCUSSION:
      Penile biopsy has an important role in the diagnosis of penile dermatoses. In our
      study, in 44.9% of cases, a clinically unsuspected diagnosis was identified or a
      differential diagnosis was resolved.

PMID- 22963961
TI  - [Occupational dermatitis in cleaning and maintenance workers. Analysis of 769
      cases declared to the Caisse Nationale d'Assurance Maladie des Travailleurs
      Salaries between 2004 and 2007].
AB  - BACKGROUND: Employees active in the cleaning and maintenance industry (CMI) are
      particularly exposed to occupational eczema (OE), which affects the hands in 80
      to 90% of cases. This risk of OCE in France was evaluated using data collected by
      the Occupational Risks Division of the French National Health Insurance Fund for
      Salaried Workers (CNAMTS). PATIENTS AND METHODS: All cases of OE among CMI
      employees declared to and recognized by the CNAMTS between 1st January 2004 and
      31st December 2007 were selected. The following parameters were noted in each
      case: age, gender, trade in question, National Health Insurance Office of
      residence, causal agent and number of days of sick leave. The incidence per
      100,000 employees could be determined from the total number of employees followed
      up by occupational medicine and the numbers working in the CMI. RESULTS: For the
      4 years studied, 769 cases of OE were reported in CMI workers representing 2.6%
      of the salaried employee population. The annual incidence of OE was 43.5 per
      100,000 employees. There was a marked female predominance (75.7%). OE led to loss
      of 32,714 workdays. CONCLUSION: This is the first study conducted in France about
      OE among NIS employees. It highlights the socioeconomic impact of OE. The
      difficulties of interpretation show the limits of recognition of occupational
      disease. Analysis of cases of OE in France and monitoring require the development
      of a specific database to clarify risk situations and identify priority regional
      and national preventive actions.

PMID- 22963962
TI  - [Antibiotic treatment of hidradenitis suppurativa].
AB  - Bacterial infection plays an important role in hidradenitis suppurativa (HS).
      This infection has a number of unique features: chronicity, absence of lymph node
      involvement, and absence in most cases of acute super-infection by Staphylococcus
      aureus and/or streptococci. Treatment is based mainly on antibiotics. Various
      bacteria are involved; they are often part of the resident flora and may combine
      in polymicrobial infections, and they consist mainly of two families: coagulase
      negative staphylococci (CNS) and anaerobes. Numerous antibiotics are active
      against CNS: betalactamins, lincosamides, macrolides, rifampicin, tetracyclines
      and fluoroquinolones. Antibiotics active against anaerobes include metronidazole,
      betalactamins, lincosamides and one fluoroquinolone (moxifloxacine). Antibiotics
      are given per os and in combination. Treatment is usually long-term, with a
      frequent need for maintenance therapy. It has to be tailored to various clinical
      situations: intermittent development, in which "abortive" emergency treatment is
      used; major or major continuous forms, where combined antibiotics are used, most
      frequently rifampicin and clindamycin. The global treatment strategy involves a
      surgical approach, which can be aided but not replaced by antibiotics. While the
      risks of long-term antibiotic use are reduced in this specific population of
      "healthy" young adults, they are not absent.

PMID- 22963963
TI  - [Unusual clinical presentation of cutaneous leishmaniasis in three diabetic
      patients].
AB  - INTRODUCTION: Cutaneous leishmaniasis (CL) is a parasitic infection characterized
      by significant clinical variability. Unusual and atypical clinical aspects of
      infection have been reported in immunodeficient patients or associated with
      particular parasite species. We report three cases of CL from foci of Leishmania
      major with a particular clinical presentation in diabetic patients. OBSERVATIONS:
      Patient 1: a 37-year-old man was admitted to the dermatology department for
      cutaneous vegetative ulcers spreading to the dorsal surface of the foot. History
      taking revealed a stay in Er-Rachidia (East of Morocco, a known focus of CL L.
      major) six weeks earlier. Diabetes mellitus type I was discovered during
      hospitalization. The patient's 43-year-old sister (patient 2), diabetic for 6
      years, consulted for a single leg ulcer appearing 3 months after the same trip to
      Er-Rachidia. Patient 3: a 61-year-old patient with a 7-year history of diabetes
      and under oral antidiabetics presented an extended vegetative lesion of the
      posterior surface of the leg 2 months after staying in Er-Rachidia. A diagnosis
      of CL was retained on the basis of epidemiology and history (living in an endemic
      areas of leishmaniasis), coupled in patients 1 and 3 with microbiological
      evidence involving identification of Leishmania bodies in skin smears or skin
      biopsies. All patients were treated with two intra-lesional injections per week
      of meglumine antimony (Glucantime((r))) for 6 weeks. The outcome was marked in
      all cases by healing of lesions and persistent pigmented scarring. DISCUSSION: We
      described three particular clinical aspect of CL emerging from a known focus of
      L. major, where infection is classically associated with vegetative or ulcero
      vegetative lesions. This unusual profile suggests the role of factors related to
      parasite species and/or diabetes found in our three patients.

PMID- 22963964
TI  - [Riga-Fede disease].
AB  - INTRODUCTION: Riga-Fede disease is a benign affection of the oral mucosa which
      has been poorly described in the literature. This entity of unknown
      ethiopathogenicity is sometimes revealing of dysautonomic or neuropsychic
      disorders. We report a new case. CASE REPORT: A 10-month-old girl was referred to
      us for a unique deep ulceration of the lower lingual apex, in a context of right
      basal pneumopathy. Samples were negative for bacteriological, virological and
      mycological analysis. After successful treatment of the pneumopathy, the
      ulceration was unchanged and we diagnosed Riga-Fede disease. DISCUSSION: Our
      observation is representative of the Riga-Fede cases previously described in the
      literature, comparing the age of onset, the topography and the ulceration type.
      We did not diagnose any dysautonomic or neuropsychic disorder as reported in some
      cases. Suppression of the lingual trauma resulted in healing of the ulceration.

PMID- 22963965
TI  - [Branchio-oculo-facial syndrome].
AB  - BACKGROUND: Branchio-Oculo-Facial Syndrome (BOFS, MIM#113620) is a rare,
      polymalformational disorder with cutaneous and ocular abnormalities and
      characteristic facial anomalies. It is an autosomal dominant developmental
      disorder caused by mutations or deletions in the transcription factor AP-2 alpha
      gene (TFAP2A, 6p24). We report a new case of atypical BOFS with a unilateral
      cervical cutaneous defect. PATIENT AND METHODS: A 5-year-old girl was admitted to
      our dermatology department for a congenital, linear, erythematous cutaneous
      anomaly on the right side of her neck. There was no family history. She also
      presented characteristic facial and ocular anomalies. BOFS was suspected. TFAP2A
      molecular analysis revealed a heterozygous missense mutation c.767C>T
      (p.Ala256Val). DISCUSSION: BOFS is variable and remains unknown to dermatologists
      in spite of distinctive cutaneous features. Identification of this syndrome is
      important to improving medical care (multidisciplinary care, further tests,
      genetic counselling). We report a case of atypical BOFS with a unilateral
      cervical cutaneous defect in one patient and bilateral cutaneous anomalies in the
      other four patients. In agreement with the literature, there did not appear to be
      mutation-specific genotype-phenotype correlations.

PMID- 22963966
TI  - [Infantile bullous pemphigoid].
AB  - BACKGROUND: Bullous pemphigoid (BP) is a form of autoimmune bullous disease
      commonly seen in adults but rare amongst children. Only a few cases have been
      described in children after vaccination. This article reports a new case of BP
      that occurred in an infant after a first vaccination. PATIENTS AND METHODS: A 3
      month-old girl presented a bullous eruption 2 weeks after a first injection of
      Infanrix Quinta((r)) and Prevenar((r)). The eruption began on her palms and
      soles. It was associated with urticaria-like lesions on her thighs, chest and
      abdomen. A histological skin examination and direct immunofluorescence showed
      dermal-epidermal cleavage and IgG and C3 deposits in the epidermal basement
      membrane zone, which are typical features of BP. No antibodies against basement
      membrane were seen. Clinical remission was observed after 5 weeks of treatment
      with dermal-corticosteroids. Resumption of the vaccination schedule did not
      induce any recurrence of the disease. DISCUSSION: The clinical presentation of BP
      amongst children differs from that seen in adults, notably in terms of the
      predominance of palmoplantar lesions in children aged less than 1 year. In
      addition, lesions on mucous membrane are more frequently reported amongst older
      children. Histological findings are similar in all age groups. The outbreak of BP
      due to a vaccinal antigen appears hypothetical. However, continuation of the
      vaccination schedule did not induce any recurrence. Moreover, it is a rare
      disease amongst children despite the frequency of vaccinations in this
      population. CONCLUSION: Childhood BP is a diagnosis that should be considered in
      any case of bullous eruption, in particular if the palms and soles are affected.
      It is a benign disease that resolves in less than a year under treatment. The
      current data do not incriminate vaccines in the outbreak of childhood BP and
      suggest that continuation of vaccination is not contraindicated.

PMID- 22963967
TI  - [Efficacy of diuretics in the treatment of Morbihan's disease: three cases].
AB  - BACKGROUND: Morbihan's disease (MD), also known as 'persistent facial oedema' or
      'rosaceous lymphoedema', is an uncommon facial condition that is difficult to
      treat. Its cause remains unclear. AIM: We report three new cases of solid
      persistent facial oedema, which, after treatment with furosemide, showed dramatic
      improvement. PATIENTS AND METHODS: Three men (respectively aged 38, 66 and 76
      years) presented Morbihan's disease progressing respectively for 2, 5 and 8
      years. These patients presented with facial oedema, mainly affecting the eyelids.
      The diagnosis of MD was based on clinical and laboratory criteria (after
      exclusion of other aetiologies such as sarcoidosis, lupus erythematosus, facial
      demodicidosis and rosacea). After several unsuccessful treatments (tetracyclines,
      synthetic antimalarials, danazol, systemic steroids and isotretinoin), the
      patients received diuretics: furosemide (60 mg/d) in two cases and spironolactone
      75 mg twice daily for the third patient. The patients were evaluated after 1
      month, then every 3 months. RESULTS: Regression of oedema was complete or almost
      complete with follow-up of between 1 and 16 years. No adverse effects were
      reported. DISCUSSION: Treatment of Morbihan's disease remains difficult and
      empirical. Diuretics may be of value since they help significantly reduce
      swelling even if they do not definitely cure patients.

PMID- 22963968
TI  - [Hookworm-related cutaneous larva migrans in dermatology departments in Lome,
      Togo, between 2006 and 2011].

PMID- 22963969
TI  - [Circumcision-induced penodynia].

PMID- 22963970
TI  - [Stem cells in dermatology: concept and medical interest].

PMID- 22963971
TI  - [Pigmentary mosaicism].

PMID- 22963972
TI  - [Tretinoin and scrotal ulceration].

PMID- 22963973
TI  - [Dermatofibrosarcoma protuberans].

PMID- 22963974
TI  - [Antineutrophil cytoplasmic antibodies: what the dermatologist should know].

PMID- 22963975
TI  - [Factitious purpura chin].

PMID- 22963976
TI  - [Subcutaneous fat necrosis and hypercalcemia following therapeutic hypothermia].

PMID- 22963977
TI  - [Large ecchymotic lesions revealing homozygous protein C deficiency].

PMID- 22963978
TI  - [RHBDF2 mutations in familial palmoplantar keratoderma associated with tylosis
      oesophageal cancer].

PMID- 22963979
TI  - Ecodynamics of PAHs at a peri-urban site of the French Mediterranean Sea.
AB  - The PAH contamination level and biochemical composition of sinking particles and
      surficial sediments (0-0.5 cm layer) were assessed at a rural coastal site in the
      northwestern Mediterranean Sea. Surficial sediment contamination (~20 ng g(-1))
      was considerably lower than at other Mediterranean sites, yet particles collected
      in sediment traps had 6-8 times more PAH. Contaminated particles were mostly
      marine in origin. Temporal variation of contamination levels correlated with
      organic content of the particles, but some of the observed variability could be
      attributed to seasonal changes in pyrolytic PAH production. Sinking organic
      particles were potentially as readily digestible as surficial sediments for
      prospective consumers however, transfer of PAHs along the benthic food chain is
      probably enhanced because of the particles' higher nutritional value.

PMID- 22963980
TI  - Unfolding neutron spectra obtained from BS-TLD system using genetic algorithm.
AB  - Due to the variability of neutron spectrum within the same environment, it is
      essential that the spectral distribution as a function of energy should be
      characterized. The precise information allows radiological quantities
      establishment related to that spectrum, but it is necessary that a spectrometric
      system covers a large interval of energy and an unfolding process is appropriate.
      This paper proposes use of a technique of Artificial Intelligence (AI) called
      genetic algorithm (GA), which uses bio-inspired mathematical models with the
      implementation of a specific matrix to unfolding data obtained from a combination
      of TLDs embedded in a BS system to characterize the neutron spectrum as a
      function of energy. The results obtained with this method were in accordance with
      reference spectra, thus enabling this technique to unfold neutron spectra with
      the BS-TLD system.

PMID- 22963981
TI  - Phonological processing skills and its relevance to receptive vocabulary
      development in children with early cochlear implantation.
AB  - OBJECTIVES: The purposes of this study were to investigate phonological
      processing skills for children with cochlear implants (CIs) in comparison with
      children with normal hearing (NH), and to assess whether phonological processing
      skills can explain variance in receptive vocabulary scores in children with CIs.
      METHODS: Twenty-five deaf children who received a CI before 2 years of age were
      included in this study, and they ranged from 4 years to 6 years 11 months. Twenty
      five children with NH as a control group were matched to children with CIs on the
      basis of chronological age with 3 months. Phonological processing skills were
      measured by the phonological awareness (PA), nonword repetition (NWR), and rapid
      automatized naming (RAN) tasks. Receptive vocabulary skills were also tested by
      the Peabody Picture Vocabulary Test - Korean version. RESULTS: Children with CIs
      performed significantly lower than children with NH on PA (p<.05) and NWR
      (p<.001) tasks. Children with CIs showed slower naming speed than children with
      NH, which did not reach the significant level (p>.05). Among phonological
      processing skills, PA contributed significant amount to receptive vocabulary
      skills in children with CIs (p<.001). CONCLUSIONS: Children with early
      implantation receive substantial benefits for developing lexical access skills.
      However, children with CIs showed delays in PA and NWR in comparison with age
      matched children with NH. For children with CIs, PA among phonological processing
      skills plays an important role of developing receptive vocabulary skills.

PMID- 22963982
TI  - Darapladib effect on circulating high sensitive troponin in patients with acute
      coronary syndromes.
AB  - OBJECTIVES: We compared the incidence of late increase in hs-cTnI between ACS and
      non-ACS patients treated with standard of care with or without darapladib.
      METHODS: A total of 323 (161 ACS and 162 non-ACS patients) were included. High
      sensitivity troponin I was measured at baseline and at 4, 13, 26 and 52 weeks.
      RESULTS: ACS patients had statistically higher hs-cTnI values during longer term
      follow-up at which these patients were no longer in the acute setting of
      myocardial ischemia, but were regarded to have stable CAD (mean hsTnI value in
      ACS patients: 1.180 versus 0.886 ng/L in non-ACS patients, p = 0.02).
      Multivariate logistic regression revealed three predictors of any 2-fold increase
      in hs-cTnI levels compared to the previous visit when interactions were not
      considered. Treatment with darapladib (adjusted OR 0.53; 95% CI: 0.30-0.92) and
      initial presentation with ACS (adjusted OR 0.42; 95% CI: 0.23-0.77) were
      associated with less frequent occurrence of a 2-fold increase in hs-cTnI levels.
      In contrast, diabetes was associated with a higher incidence of 2-fold increases
      in hs-cTnI levels (adjusted OR 2.20; 95% CI: 1.04-4.64). Logistic regression to
      predict any 2-fold increase in hs-cTnI by ACS status showed that in the ACS
      group, treatment with darapladib decreased the risk of elevation of hs-cTnI (OR
      0.219; 95% CI: 0.087, 0.553, p = 0.0013). CONCLUSION: In patients with ACS,
      treatment with darapladib is associated with less increase in cardiac troponin I
      compared to standard of care alone. This beneficial effect may be associated with
      darapladib's capability of reducing necrotic core in coronary plaques.

PMID- 22963983
TI  - Enhanced CD36 expression changes the role of Nrf2 activation from anti
      atherogenic to pro-atherogenic in apoE-deficient mice.
AB  - Oxidative stress has been implicated as a causative factor of atherosclerosis.
      Defense systems against oxidative stress are maintained by radical scavenging
      antioxidants and/or by regulating the expression of antioxidant genes by
      activating oxidative stress-sensitive transcription factor: nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2). We investigated the anti-atherogenic effects
      of three synthesized compounds (shogaol A: radical scavenging antioxidant
      activity; shogaol N: Nrf2-activating activity; shogaol N + A: both activities)
      and curcumin (both activities) in apolipoprotein E (apoE)-deficient mice. We
      expected compounds with both activities to have additive or synergistic anti
      atherogenic effects; however, atherosclerosis was exacerbated significantly by
      curcumin and slightly by shogaol N + A. Shogaol A, shogaol N, and shogaol N + A
      showed no significant effect on atherosclerosis development. Immunohistochemical
      analysis of the aorta revealed that expression of CD36, an Nrf2-regulated gene,
      was strongly induced by treatment with curcumin. The total antioxidant capacity
      of plasma collected from mice administered the three compounds was evaluated
      using a hydrophilic probe, pyranine. Shogaol N or shogaol N + A significantly
      enhanced the antioxidant capacity of plasma, whereas shogaol A and curcumin did
      not show this activity. The concentrations of the three shogaol derivatives in
      plasma were similar (approximately 100 nM), while that of curcumin was much
      lower. These results suggest that plasma antioxidant capacity is maintained at
      high levels via Nrf2 activation and that CD36 expression enhances atherosclerosis
      development.

PMID- 22963985
TI  - HDL and adaptive immunity: a tale of lipid rafts.

PMID- 22963984
TI  - The levels of MDA-LDL in circulating immune complexes predict myocardial
      infarction in the VADT study.
AB  - OBJECTIVE: Circulating immune complexes (IC) containing modified forms of LDL
      (mLDL) are strongly pro-inflammatory and strong predictors of cardiovascular
      disease (CVD) progression in type 1 diabetes. The present study was undertaken to
      determine whether the levels of oxidized LDL (oxLDL), malondialdehyde-LDL (MDA
      LDL) and advanced glycation end products-LDL (AGE-LDL) in IC predict incident CVD
      events in type 2 diabetes (VADT cohort). METHODS AND RESULTS: Levels of mLDL in
      IC were measured in 907 patients of the VADT cohort, a median of two years after
      entry into the study. Participants were followed for an average of 3.7 years for
      vascular outcomes. Hazard ratios (HRs) for CV endpoints in relation to mLDL-IC
      quartiles were calculated by Cox proportional hazard models. The primary
      composite CVD endpoint included documented myocardial infarction (MI); stroke;
      death from CVD; congestive heart failure; cardiac, cerebrovascular, or peripheral
      VD surgical intervention; inoperable CVD; and amputation for ischemic gangrene.
      During follow-up, 4.7% and 16.8% of participants had an MI or a composite
      endpoint, respectively. After adjustments by conventional risk factors,
      individuals in the highest quartile of MDA-LDL-IC were at higher risk of MI [HR =
      2.44 (95% CI: 1.03, 5.77)] and composite endpoint [HR = 1.71 (95% CI: 1.04,
      2.80)], relative to individuals in the lowest quartile. Similar comparisons for
      oxLDL and AGE-LDL levels yielded HR values of 1.08 and 1.31 for MI and 0.91 and
      1.34 for composite endpoint. CONCLUSIONS: Our study indicates that high levels of
      MDA-LDL in isolated IC predict future MI and acute CV events in patients with
      type 2 diabetes.

PMID- 22963986
TI  - Seasonal prevalence of malaria vectors and entomological inoculation rates in the
      rubber cultivated area of Niete, South Region of Cameroon.
AB  - BACKGROUND: Development of large scale agro-industries are subject to serious
      environmental modifications. In malaria endemic areas this would greatly impact
      on the transmission paradigm. Two cross-sectional entomological surveys to
      characterize the Anopheles fauna and their entomological inoculation rates were
      conducted during May 2010 (peak rainy season) and December 2010 (peak dry season)
      in the intense rubber cultivated area of Niete in southern forested Cameroon.
      METHODS: Mosquitoes were sampled by night collections on human volunteers,
      identified morphologically and members of the Anopheles gambiae complex further
      identified to species and molecular form. Parity status was determined following
      the dissection of the ovaries. Plasmodium falciparum circumsporozoite antigen
      indices were estimated after the identification of CS antigen by ELISA and the
      average entomological inoculation rates determined. RESULTS: A total of 1187
      Anopheles was collected, 419 (35.3%) in the rainy season and 768 (64.7%) in the
      dry season. Species found were the M molecular form of An. gambiae s.s (66.8%),
      An. ziemanni (28.3%), An. paludis (4.7%), An. smithii (0.2%). An. gambiae M-form
      was the principal species in the dry (56.2%) and wet (86.2%) seasons. Average
      overall entomological inoculation rate for the malaria vectors varied between the
      dry season (1.09 ib/p/n) and the rainy season (2.30 ib/p/n). CONCLUSIONS: Malaria
      transmission in Niete occurs both in the dry and rainy season with the
      intensities peaking in the dry season. This is unlike previous studies in other
      areas of southern forested Cameroon where transmission generally peaks in the
      rainy season. Environmental modifications due to agro-industrial activities might
      have influenced vector distribution and the dynamics of malaria transmission in
      this area. This necessitates the possible implementation of control strategies
      that are related to the eco-geography of the area.

PMID- 22963987
TI  - Integration of research advances in modelling and monitoring in support of WFD
      river basin management planning in the context of climate change.
AB  - The integration of scientific knowledge about possible climate change impacts on
      water resources has a direct implication on the way water policies are being
      implemented and evolving. This is particularly true regarding various technical
      steps embedded into the EU Water Framework Directive river basin management
      planning, such as risk characterisation, monitoring, design and implementation of
      action programmes and evaluation of the "good status" objective achievements (in
      2015). The need to incorporate climate change considerations into the
      implementation of EU water policy is currently discussed with a wide range of
      experts and stakeholders at EU level. Research trends are also on-going, striving
      to support policy developments and examining how scientific findings and
      recommendations could be best taken on board by policy-makers and water managers
      within the forthcoming years. This paper provides a snapshot of policy
      discussions about climate change in the context of the WFD river basin management
      planning and specific advancements of related EU-funded research projects.
      Perspectives for strengthening links among the scientific and policy-making
      communities in this area are also highlighted.

PMID- 22963988
TI  - Drought and climatic change impact on streamflow in small watersheds.
AB  - The paper presents a comprehensive, thought simple, methodology, for forecasting
      the annual hydrological drought, based on meteorological drought indications
      available early during the hydrological year. The meteorological drought of 3, 6
      and 9 months is estimated using the reconnaissance drought index (RDI), whereas
      the annual hydrological drought is represented by the streamflow drought index
      (SDI). Regression equations are derived between RDI and SDI, forecasting the
      level of hydrological drought for the entire year in real time. Further, using a
      wide range of scenarios representing possible climatic changes and drought events
      of varying severity, nomographs are devised for estimating the annual streamflow
      change. The Medbasin rainfall-runoff model is used to link meteorological data to
      streamflow. The later approach can be useful for developing preparedness plans to
      combat the consequences of drought and climate change. As a case study, the area
      of N. Peloponnese (Greece) was selected, incorporating several small river
      basins.

PMID- 22963989
TI  - Interactions between modafinil and cocaine during the induction of conditioned
      place preference and locomotor sensitization in mice: implications for addiction.
AB  - Modafinil is a wake-promoting drug effective at enhancing alertness and attention
      with a variety of approved and off-label applications. The mechanism of modafinil
      is not well understood but initial studies indicated a limited abuse potential. A
      number of recent publications, however, have shown that modafinil can be
      rewarding under certain conditions. The present study assessed the reinforcing
      properties of modafinil using conditioned place preference and locomotor
      sensitization in mice. Experiment 1 examined a high dose of modafinil (75 mg/kg)
      as well as its interactions with cocaine (15 mg/kg). Cocaine alone and modafinil
      co-administered with cocaine induced sensitization of locomotor activity;
      modafinil alone showed little or no locomotor sensitization. Animals given
      modafinil alone, cocaine alone, and modafinil plus cocaine exhibited a strong and
      roughly equivalent place preference. When tested for sensitization using a low
      challenge dose of modafinil, cross-sensitization was observed in all cocaine
      pretreated mice. Experiment 2 examined a low dose of modafinil that is similar to
      the dose administered to humans and has been shown to produce cognitive
      enhancements in mice. Low dose modafinil (0.75 mg/kg) did not produce conditioned
      place preference or locomotor sensitization. Together, these results suggest that
      modafinil has the potential to produce reward, particularly in cocaine addicts,
      and should be used with caution. However, the typical low dose administered
      likely moderates these effects and may account for lack of addiction seen in
      humans.

PMID- 22963990
TI  - Further characterization of repetitive behavior in C58 mice: developmental
      trajectory and effects of environmental enrichment.
AB  - Aberrant repetitive behaviors are commonly observed in a variety of
      neurodevelopmental, neurological, and neuropsychiatric disorders. Little is known
      about the specific neurobiological mechanisms that underlie such behaviors,
      however, and effective treatments are lacking. Valid animal models can aid
      substantially in identifying pathophysiological factors mediating aberrant
      repetitive behavior and aid in treatment development. The C58 inbred mouse strain
      is a particularly promising model, and we have further characterized its
      repetitive behavior phenotype. Compared to C57BL/6 mice, C58 mice exhibit high
      rates of spontaneous hindlimb jumping and backward somersaulting reaching adult
      frequencies by 5 weeks post-weaning and adult temporal organization by 2 weeks
      post-weaning. The development of repetitive behavior in C58 mice was markedly
      attenuated by rearing these mice in larger, more complex environments. In
      addition to characterizing repetitive motor behavior, we also assessed related
      forms of inflexible behavior that reflect restricted and perseverative
      responding. Contrary to our hypothesis, C58 mice did not exhibit increased marble
      burying nor did they display reduced exploratory behavior in the holeboard task.
      The C58 strain appears to be a very useful model for the repetitive motor
      behavior characteristic of a number of clinical disorders. As an inbred mouse
      strain, studies using the C58 model can take full advantage of the tool kit of
      modern genetics and molecular neuroscience. This technical advantage makes the
      model a compelling choice for use in studies designed to elucidate the etiology
      and pathophysiology of aberrant repetitive behavior. Such findings should, in
      turn, translate into effective new treatments.

PMID- 22963991
TI  - A food-associated CS activates c-Fos in VTA DA neurons and elicits conditioned
      approach.
AB  - Neutral stimuli associated with unconditioned stimuli (USs) acquire the ability
      to act as conditioned stimuli (CSs), which can elicit behaviors similar to the US
      with which they are associated. The neural mechanisms by which this occurs are
      not fully known. We have previously proposed a model stipulating CSs function as
      such because they acquire the capacity to activate dopamine (DA) neurons at the
      level of the ventral tegmental area (VTA). In the present experiments we
      hypothesized that a food-associated CS (light), which demonstrably functions as
      such by eliciting conditioned responses (CRs), comes to acquire the capacity to
      activate VTA DA neurons. In Experiment 1, rats were allowed to eat or not eat
      food (food being the US). In Experiment 2, rats were trained to retrieve food
      pellets after light presentations (the CS) and then tested for the expression of
      the food checking response (the CR) with only CS presentations. In Experiment 1,
      eating food (exposure to the US) caused a significantly greater number of VTA DA
      (TH-labeled) cells to express c-Fos than not eating. In Experiment 2, CS (light)
      presentations caused a significant amount of conditioned approach and a
      significantly greater number of VTA TH-labeled (DA) cells to express c-Fos. These
      findings support our model stipulating that conditioned approach learning occurs
      when CSs acquire the capacity to cause conditioned activation of VTA DA neurons.

PMID- 22963992
TI  - Anxiolytic effects of ethanol are partially related to a reduced expression of
      adenylyl cyclase 5 but not to MU-opioid receptor activation in rat nucleus
      accumbens.
AB  - Anxiolytic effects of alcohol participate in the reinforcing properties of the
      drug, in which nucleus accumbens (NAcc) is implicated. The opioidergic system in
      NAcc is considered a main pathway involved in the emotional responses of animals:
      rats microinjected with morphine in NAcc and the systemic administration of MU
      opioid receptors (MOR) agonists yield low anxiety scores in the elevated plus
      maze (EPM), a behavioral test of anxiety. However, the specific participation of
      NAcc MOR in the anxiolytic effect of ethanol has not been studied. AC5, a cAMP
      synthezising adenylyl-cyclase, is highly expressed in NAcc; it is negatively
      coupled to MOR and has been implicated in anxiety levels of animals. We evaluated
      the anxiolytic effects of an intra-gastric administration of ethanol (2.5 g/kg)
      in animals subjected to EPM at 1, 4, and 8 h after drug or water exposure.
      Locomotion was assayed with the open-field test; we also measured accumbal AC5
      and MOR mRNA levels by RT-PCR. After 1 h, ethanol-exposed animals showed
      anxiolytic-like behavior, as well as decreased and increased AC5 and MOR
      expression in NAcc, respectively. Intra-accumbal injection of beta-funaltrexamine
      (FNA), a MOR antagonist, did not block ethanol-induced anxiolysis, rather it
      induced a tendency to increase anxiety levels in the water-exposed group. FNA
      partially decreased accumbal AC5 expression in ethanol-treated rats. We concluded
      that AC5 in NAcc is participating in the emotional effects of ethanol; that MOR
      was not mediating the drug-induced AC5 reduction in NAcc nor the ethanol-induced
      anxiolysis. MOR only might be involved in basal levels of anxiety of animals.

PMID- 22963993
TI  - Akebia Saponin D attenuates amyloid beta-induced cognitive deficits and
      inflammatory response in rats: involvement of Akt/NF-kappaB pathway.
AB  - Neuroinflammatory responses caused by amyloid beta(Abeta) play an important role
      in the pathogenesis of Alzheimer's disease (AD). Abeta is known to be directly
      responsible for the activation of glial cells and induction of apoptosis. Akebia
      Saponin D (ASD) is extracted from a traditional herbal medicine Dipsacus asper
      Wall, which has been shown to protect against ibotenic acid-induced cognitive
      deficits and cell death in rats. In this study, we investigated the in vivo
      protective effect of ASD on learning and memory impairment induced by bilateral
      intracerebroventricular injections of Abeta1-42 using Morris water and Y-maze
      task. Furthermore, the anti-inflammatory activity and neuroprotective effect of
      ASD was examined with methods of histochemistry and biochemistry. These data
      showed that oral gavage with ASD at doses of 30, 90 and 270 mg/kg for 4 weeks
      exerted an improved effect on cognitive impairment. Subsequently, the ASD
      inhibited the activation of glial cells and the expression of tumor necrosis
      factor (TNF)-alpha, interleukin-1 beta (IL-1beta) and cyclooxygenase-2 (COX-2) in
      rat brain. Moreover, ASD afforded beneficial actions on inhibitions of Akt and
      IkappaB kinase (IKK) phosphorylations, as well as nuclear factor kappaB (NF
      kappaB) activation induced by Abeta1-42. These results suggest that ASD may be a
      potential agent for suppressing both Alzheimer's disease-related
      neuroinflammation and memory system dysfunction.

PMID- 22963995
TI  - Novel therapeutic targets in depression: minocycline as a candidate treatment.
AB  - Mood disorders are marked by high rates of non-recovery, recurrence, and
      chronicity, which are insufficiently addressed by current therapies. Several
      patho-etiological models have been proposed that are not mutually exclusive and
      include but are not limited to the monoamine, inflammatory, neurotrophic,
      gliotrophic, excitatory, and oxidative stress systems. A derivative of these
      observations is that treatment(s) which target one or more of these mechanistic
      steps may be capable of mitigating, or preventing, disparate psychopathological
      features. Minocycline is an agent with pleiotropic properties that targets
      multiple proteins and cellular processes implicated in the patho-etiology of mood
      disorders. Moreover, preclinical and preliminary clinical evidence suggests that
      minocycline possesses antidepressant properties. Herein, we provide the rationale
      for conducting a randomized, controlled trial to test the antidepressant
      properties of minocycline.

PMID- 22963994
TI  - Reversible deafferentation of the adult zebrafish olfactory bulb affects
      glomerular distribution and olfactory-mediated behavior.
AB  - The olfactory system is a useful model for studying central nervous system
      recovery from damage due to its neuroplasticity. We recently developed a novel
      method of deafferentation by repeated exposure of Triton X-100 to the olfactory
      organ of adult zebrafish. This long-term, reversible method of deafferentation
      allows both degeneration and regeneration to be observed in the olfactory bulb.
      The aim of the present study is to examine olfactory bulb innervation, glomerular
      patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment
      and the potential for recovery following cessation of treatment. Olfactory bulbs
      of control, chronic-treated, and recovery animals were examined for the presence
      or absence of glomeruli that have been identified in the zebrafish glomerular
      map. Following chronic treatment, the number of glomeruli was dramatically
      reduced; however, partial innervation remained in the lateral region of the bulb.
      When animals were given time to recover, complete glomerular distribution
      returned. A behavioral assay was developed to determine if innervation remaining
      correlated with behavior of the fish. Chronic-treated fish did not respond to
      odorants involved with social behavior but continued to react to odorants that
      mediate feeding behavior. Following recovery, responses to odorants involved with
      social behavior returned. The morphological and behavioral effects of chronic
      Triton X-100 treatment in the olfactory system suggest there may be differential
      susceptibility or resistance to external damage in a subset of sensory neurons.
      The results of this study demonstrate the remarkable regenerative ability of the
      olfactory system following extensive and long-term injury.

PMID- 22963996
TI  - Possible involvement of histone acetylation in the development of emotional
      resistance to stress stimuli in mice.
AB  - Recent reports have implied that aberrant biochemical processes in the brain
      frequently accompany subtle shifts in the cellular epigenetic profile that might
      underlie the pathogenic progression of psychiatric disorders. Furthermore,
      certain antidepressants or mood stabilizers have been reported to have the
      ability to modulate epigenetic parameters. We previously reported that
      pretreatment of mice with 5-HT(1A) receptor agonists 24 h before testing
      suppressed the decrease in emotional behaviors induced by exposure to acute
      restraint stress. Based on this finding, the aim of the present study was to
      examine the association between the development of emotional resistance to stress
      stimuli and the modulation of an epigenetic parameter, particularly histone
      acetylation. We found that acetylated histone H3 was increased in the hippocampus
      of mice that had developed resistance to emotional stress by pretreatment with
      flesinoxan (1 mg/kg, i.p.) 24 h before testing. On the other hand, pretreatment
      with benzodiazepine anxiolytic diazepam (1 mg/kg, i.p.) did not have similar
      effects. Interestingly, similar to flesinoxan, the histone deacetylase inhibitor
      trichostatin A also protected against the emotional changes induced by acute
      restraint stress, as well as histone H3 acetylation. The present findings suggest
      that the epigenetic mechanisms of gene regulation may play an important role in
      the development of emotional resistance to stress stimuli.

PMID- 22963997
TI  - Speed of response in ultrabrief and brief pulse width right unilateral ECT.
AB  - Ultrabrief pulse width stimulation electroconvulsive therapy (ECT) results in
      less cognitive side-effects than brief pulse ECT, but recent work suggests that
      more treatment sessions may be required to achieve similar efficacy. In this
      retrospective analysis of subjects pooled from three research studies, time to
      improvement was analysed in 150 depressed subjects who received right unilateral
      ECT with a brief pulse width (at five times seizure threshold) or ultrabrief
      pulse width (at six times seizure threshold). Multivariate Cox regression
      analyses compared the number of treatments required for 50% reduction in
      depression scores (i.e. speed of response) in these two samples. The analyses
      controlled for clinical, demographic and treatment variables that differed
      between the samples or that were found to be significant predictors of speed of
      response in univariate analyses. In the multivariate analysis, older age
      predicted faster speed of response. There was a non-significant trend for faster
      time to 50% improvement with brief pulse ECT (p = 0.067). Remission rates were
      higher after brief pulse ECT than ultrabrief pulse ECT (p = 0.007) but response
      rates were similar. This study, the largest of its kind reported to date,
      suggests that fewer treatments may be needed to attain response with brief than
      ultrabrief pulse ECT and that remission rates are higher with brief pulse ECT.
      Further research with a larger randomized and blinded study is recommended.

PMID- 22963998
TI  - Self-organizing adaptive map: autonomous learning of curves and surfaces from
      point samples.
AB  - Competitive Hebbian Learning (CHL) (Martinetz, 1993) is a simple and elegant
      method for estimating the topology of a manifold from point samples. The method
      has been adopted in a number of self-organizing networks described in the
      literature and has given rise to related studies in the fields of geometry and
      computational topology. Recent results from these fields have shown that a
      faithful reconstruction can be obtained using the CHL method only for curves and
      surfaces. Within these limitations, these findings constitute a basis for
      defining a CHL-based, growing self-organizing network that produces a faithful
      reconstruction of an input manifold. The SOAM (Self-Organizing Adaptive Map)
      algorithm adapts its local structure autonomously in such a way that it can match
      the features of the manifold being learned. The adaptation process is driven by
      the defects arising when the network structure is inadequate, which cause a
      growth in the density of units. Regions of the network undergo a phase transition
      and change their behavior whenever a simple, local condition of topological
      regularity is met. The phase transition is eventually completed across the entire
      structure and the adaptation process terminates. In specific conditions, the
      structure thus obtained is homeomorphic to the input manifold. During the
      adaptation process, the network also has the capability to focus on the
      acquisition of input point samples in critical regions, with a substantial
      increase in efficiency. The behavior of the network has been assessed
      experimentally with typical data sets for surface reconstruction, including
      suboptimal conditions, e.g. with undersampling and noise.

PMID- 22963999
TI  - Understanding how drivers learn to anticipate risk on the road: A laboratory
      experiment of affective anticipation of road hazards.
AB  - This study examines whether there is evidence that converging theories from the
      domains of risk and decision making, neuroscience, and psychology can improve our
      understanding of how drivers learn to appraise on-the-road hazards. Within the
      domain of decision making it is suggested that there are two distinct ways in
      which humans appraise risk: risk as feelings and risk as analysis. Meanwhile,
      current neurological theory, in the form of the Somatic Marker Hypothesis,
      supports the role of feelings and emotion as an evolved automated system of human
      risk appraisal that biases judgment and decision making. This study used skin
      conductance responses (SCRs) to measure learner, novice and experienced drivers'
      psycho-physiological responses to the development of driving hazards. Experienced
      drivers were twice as likely to produce an SCR to developing hazards as novice
      drivers and three times as likely when compared with learner drivers. These
      differences maintained significance when age, gender and exposure were controlled
      for. Further analysis revealed that novice drivers who had less than 1000 miles
      driving experience had anticipatory physiological responses similar to learner
      drivers, whereas novices who had driven more than 1000 miles had scores
      approaching those of experienced drivers. This demonstrated a learning curve
      mediated by driving experience supporting experiential learning as proposed
      within the Somatic Marker Hypothesis. A differentiation between cognitive and
      psycho-physiological responses was also found supporting theory that
      distinguishes between conscious and non-conscious risk appraisal.

PMID- 22964000
TI  - [A policy of selective episiotomy in a ward: an example of medical professional
      assessment].
AB  - OBJECTIVES: To reduce the episiotomy rates, according to the Clinical Practice
      Guidelines, of 2005, from the French College of Obstetricians and Gynaecologists.
      PATIENTS AND METHODS: A cross sectional study was conducted, in the university
      hospital maternities (Maternity 1 and 2) with a retrospective record from medical
      files. Patients who had delivered in those maternities, by vaginal route, after
      22 weeks amenorrhea were eligible. The global rate of episiotomy was analysed
      from 2006 to 2008. A descriptive clinical study was performed with a
      retrospective analysis (from July to December 2005 on 100 medical files and from
      July to December 2007 on 85 files). Besides, a study of episiotomy rate was
      conducted from 2006 to 2008. Improvement actions were developed between the two
      phases of assessment of the audit: sharing and comparing the results to
      standardized episiotomy rates, and elaborating an informatized regional
      perinatality file with episiotomy related items and national recommendations.
      RESULTS: Episiotomy rate decreased during the study, from 22.35% in 2005 to
      19.34% in 2008, in the Ward 1 (p<0.0001) and from 33.62% in 2005 to 17.93% en
      2008 (p<0.0001) in the Ward 2. An improvement was observed between the two
      periods of audits, for each item of the chart but without statistical
      signification. DISCUSSION AND CONCLUSION: Theses procedures have led to a
      positive impact on practices thanks to the work group and because of the politics
      of the perinatal network in favour of an episiotomy reduction. We hope these
      results could be improved in the future.

PMID- 22964002
TI  - AIDS patients with tuberculosis: characteristics and trend of cases reported to
      the National AIDS Registry in Italy--1993-2010.
AB  - BACKGROUND: The co-infection of tuberculosis (TB) and human immunodeficiency
      virus (HIV) continue to be a severe problem in the European region. We estimated
      the extent of this phenomenon in Italy, describing and analysing the
      characteristics of persons with acquired immune deficiency syndrome (AIDS) and TB
      reported to the National AIDS Registry. METHODS: We analysed the cases of TB
      reported to the National AIDS Registry in Italy since 1993, the year in which TB
      was introduced as an AIDS-defining disease. RESULTS: From 1993 to 2010, 45,403
      cases of AIDS were reported; among these, 4075 (8.9%) had TB (any location).
      Since 1993, there has been a progressive increase in the proportion of persons
      with TB, from 6.8% in 1993 to 11.0% in 2010. Men accounted for 76.3%; the median
      age at diagnosis was 35 years (interquartile range: 31-42 years), and 34.1% were
      non-nationals. Compared with AIDS cases without TB, AIDS cases with TB were
      significantly associated with young age (<=33 years), being non-Italian, having
      heterosexual contacts, living in the south of Italy, being a late tester and
      being alive at the time of data analysis. The proportion of non-nationals
      increased from 10.8% in 1993 to 64.6% in 2010. The incidence of AIDS and TB among
      non-nationals for the whole study period was 2.97 cases per 100,000 non
      nationals, compared with 0.11 cases per 100,000 Italians. CONCLUSION: These data
      suggest that the occurrence of TB among persons with AIDS is also increasing in
      Italy, with an increasing proportion of non-nationals, and emphasize the need to
      undergo HIV screening for all persons diagnosed with TB.

PMID- 22964003
TI  - Associations between active commuting and physical activity in working adults:
      cross-sectional results from the Commuting and Health in Cambridge study.
AB  - OBJECTIVE: To quantify the association between time spent in active commuting and
      in moderate to vigorous physical activity (MVPA) in a sample of working adults
      living in both urban and rural locations. METHODS: In 2009, participants in the
      Commuting and Health in Cambridge study were sent questionnaires enquiring about
      sociodemographic characteristics and weekly time spent in active commuting. They
      were also invited to wear an accelerometer for seven days. Accelerometer data
      were used to compute the time spent in MVPA. Multiple regression models were used
      to examine the association between time spent in active commuting and MVPA.
      RESULTS: 475 participants (70% female) provided valid data. On average,
      participants recorded 55 (SD: 23.02) minutes of MVPA per day. For women,
      reporting 150 or more minutes of active commuting per week was associated with an
      estimated 8.50 (95% CI: 1.75 to 51.26, p=0.01) additional minutes of daily MVPA
      compared to those who reported no time in active commuting. No overall
      associations were found in men. CONCLUSIONS: Promoting active commuting might be
      an important way of increasing levels of physical activity, particularly in
      women. Further research should assess whether increases in time spent in active
      commuting are associated with increases in physical activity.

PMID- 22964004
TI  - Intracrine prostaglandin E(2) signalling regulates hypoxia-inducible factor
      1alpha expression through retinoic acid receptor-beta.
AB  - We have previously found in human renal proximal tubular HK-2 cells that hypoxia-
      and all-trans retinoic acid-induced hypoxia-inducible factor-1alpha up-regulation
      is accompanied by retinoic acid receptor-beta up-regulation. Here we first
      investigated whether hypoxia-inducible factor-1alpha expression is dependent on
      retinoic acid receptor-beta and our results confirmed it since (i) hypoxia
      inducible factor-1alpha-inducing agents hypoxia, hypoxia-mimetic agent
      desferrioxamine, all-trans retinoic acid and interleukin-1beta increased retinoic
      acid receptor-beta expression, (ii) hypoxia-inducible factor-1alpha up-regulation
      was prevented by retinoic acid receptor-beta antagonist LE-135 or siRNA retinoic
      acid receptor-beta and (iii) there was direct binding of retinoic acid receptor
      beta to the retinoic acid response element in hypoxia-inducible factor-1alpha
      promoter upon treatment with all-trans retinoic acid and 16,16-dimethyl
      prostaglandin E(2). Since intracellular prostaglandin E(2) mediates hypoxia
      inducible factor-1alpha up-regulation in normoxia in HK-2 cells, we next
      investigated and confirmed, its role in the up-regulation of retinoic acid
      receptor-beta in normoxia by hypoxia-inducible factor-1alpha-inducing agents all
      trans retinoic acid, interleukin-1beta and 16,16-dimethyl-prostaglandin E(2) by
      inhibiting cyclooxygenases, prostaglandin influx transporter or EP receptors.
      Interestingly, the hypoxia-induced increase in retinoic acid receptor-beta
      expression and accumulation of hypoxia-inducible factor-1alpha was also blocked
      by the inhibitors tested. This is the first time, to our knowledge, that retinoic
      acid receptor-beta signalling is involved in the control of the expression of
      transcription factor hypoxia-inducible factor-1alpha in both normoxia and hypoxia
      and that retinoic acid receptor-beta expression is found to be strictly regulated
      by intracellular prostaglandin E(2). Given the relevance of hypoxia-inducible
      factor-1alpha in the kidney in terms of tumorigenesis, progressive renal failure,
      production of erythropoietin and protection in several models of renal disease,
      our results open new therapeutic opportunities on the control of hypoxia
      inducible factor-1alpha based upon the pharmacological modulation of retinoic
      acid receptor-beta, either directly or through the control of intracellular
      prostaglandin E(2) levels/signalling.

PMID- 22964005
TI  - CIL-102 induces matrix metalloproteinase-2 (MMP-2)/MMP-9 down-regulation via
      simultaneous suppression of genetic transcription and mRNA stability.
AB  - This study explores the CIL-102 suppression mechanism on matrix metalloproteinase
      2 (MMP-2) and MMP-9 expression in human leukemia K562 cells. CIL-102 attenuated
      K562 cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels.
      Moreover, CIL-102 reduced luciferase activity of MMP-2/MMP-9 promoter constructs
      and MMP-2/MMP-9 mRNA stability. CIL-102 treatment induced JNK and p38 MAPK
      activation but reduced the phospho-ERK level. Transfection of constitutively
      active MEK1 restored MMP-2 and MMP-9 promoter activity in CIL-102-treated cells,
      while suppression of p38 MAPK/JNK activation abolished CIL-102-induced MMP-2/MMP
      9 mRNA decay. CIL-102-induced p38 MAPK/JNK activation led to protein phosphatase
      2A-mediated tristetraprolin (TTP) down-regulation. The reduction in TTP-KH-type
      splicing regulatory protein (KSRP) complexes formation promoted KSRP-mediated MMP
      2/MMP-9 mRNA decay in CIL-102-treated K562 cells. Moreover, CIL-102 reduced
      invasion and MMP-2/MMP-9 expression in breast and liver cancer cells. Taken
      together, our data indicate that CIL-102 induces MMP-2/MMP-2 down-regulation via
      simultaneous suppression of genetic transcription and mRNA stability, and suggest
      a potential utility for CIL-102 in reducing MMP-2/MMP-9-mediated cancer
      progression.

PMID- 22964006
TI  - Performance of the Xpert(r) MTB/RIF assay in an active case-finding strategy: a
      pilot study from Tanzania.
AB  - In this pilot study, we evaluated the Xpert(r) MTB/RIF assay in an active case
      finding strategy, using two spot sputum samples collected within a 1-hour
      interval from household contacts of smear-positive TB index cases. Tuberculosis
      (TB) confirmed by culture served as the reference  standard. Among 219 enrolled
      contacts, the yield of active TB was 2.3%. While the sensitivity of smear
      microscopy was 60% (95%CI 14.7-94.7), Xpert MTB/RIF achieved a sensitivity of
      100% (95%CI 47.81-100.0). All culture-confirmed cases tested positive by Xpert
      MTB/RIF on the first  submitted sample, suggesting that the evaluation of only
      one sample could be sufficient for TB diagnosis in this context.

PMID- 22964007
TI  - Efficacy of an Arthrobotrys oligospora N mutant in nematode-trapping larvae after
      passage through the digestive tract of sheep.

PMID- 22964008
TI  - Antimicrobial resistance and molecular epidemiology of streptococci from bovine
      mastitis.
AB  - Streptococcus agalactiae (Group B Streptococcus, GBS), Streptococcus dysgalactiae
      subsp. dysgalactiae (Group C Streptococcus, GCS) and Streptococcus uberis are
      relevant mastitis pathogens, a highly prevalent and costly disease in dairy
      industry due to antibiotherapy and loss in milk production. The aims of this
      study were the evaluation of antimicrobial drug resistance patterns, particularly
      important for streptococcal mastitis control and the identification of strain
      molecular features. Antimicrobial resistance was assessed by disk diffusion
      against amoxicillin-clavulanic acid, cefazolin, cefoperazone, pirlimycin-PRL,
      rifaximin, streptomycin, chloramphenicol, erythromycin-ERY, gentamicin,
      tetracycline-TET and vancomycin. Genotypic relationships were identified using
      pulsed-field gel electrophoresis (PFGE), macrolide and/or tetracycline resistance
      gene profiling, GBS capsular typing, GBS virulence gene profiling and GBS and S.
      uberis multi locus sequence typing (MLST). The majority of the isolates were
      susceptible to all drugs except to aminoglycoside, macrolide, lincosamide and
      tetracycline. Close to half of the TET resistant isolates have tetO and tetK and
      almost all ERY-PRL resistant isolates have ermB. A high degree of intra-species
      polymorphism was found for GCS. The GBS belonged to ST-2, -554, -61, -23 lineages
      and five new molecular serotypes and human GBS insertion sequences in the cpsE
      gene were found. Also, GBS of serotype V with scpB and lmb seem to be related
      with GBS isolates of human origin (same ST-2 and similar PFGE). Overall our
      results suggested that different therapeutic programs may have been implemented
      in the different farms and that in most cases clones were herd-specific.

PMID- 22964009
TI  - Commentary: pain catastrophizing and low back pain: does catastrophizing predict
      progression?

PMID- 22964010
TI  - Commentary: eliminating unnecessary radiographs after spine fusion surgery:
      understanding the clinical and economic implications.

PMID- 22964011
TI  - Minimally invasive transforaminal, thoracic microscopic discectomy: technical
      report and preliminary results and complications.
AB  - BACKGROUND CONTEXT: Surgical decompression of thoracic disc herniations is
      technically challenging because retraction of the thecal sac in this area must be
      avoided. Standard open thoracic discectomy procedures require fairly extensive
      soft tissue dissection and vertebral resection to provide safe decompression of
      the spinal cord. PURPOSE: To describe our experience using a minimally invasive,
      transforaminal thoracic discectomy (MITTD) technique for the treatment of
      thoracic disc herniation. STUDY DESIGN: Technical report and preliminary results
      and complications. METHODS: Twelve patients undergoing MITTD were evaluated
      preoperatively and postoperatively at 1-, 3-, and 6-month intervals with
      neurologic examination, and were graded using the American Spinal Injury
      Association (ASIA) impairment scale and a pain visual analog scale (VAS).
      Thoracic instability and bony fusion were assessed clinically and
      radiographically with plain radiographs and computed tomography (CT) scans.
      Surgical time, blood loss, complications, and hospital length of stay were
      recorded. RESULTS: Twelve patients (seven men and five women) underwent MITTD.
      The median surgical time was 128 (80 to 185) minutes, the median estimated blood
      loss was 100 (30 to 250) mL, and the median hospital stay was 2 (1 to 4) nights.
      All discs were successfully removed, and a CT or magnetic resonance imaging
      confirmed adequate cord decompression in all cases. All patients reported easing
      of neurologic symptoms and improved walking ability. The median VAS scores
      improved from 4.5 to 2 for back pain. The ASIA score improved from D to E in the
      two patients who suffered from motor weakness. Preoperative sensory deficit was
      reduced in three of the five patients. Patients who suffered from sexual and
      urinary disturbances did not report improvement. Serious systemic or local
      complications and neurologic deterioration were not reported. CONCLUSIONS: The
      transforaminal approach enabled sufficient access to the midline of the spinal
      canal without extensive resection of the facet joint or the adjacent pedicle.
      Because most of the osseous and ligamentous structures were preserved, additional
      instrumentation was not required to prevent postoperative instability. Our early
      results suggested that minimally invasive thoracic discectomy by transforaminal
      microscopic technique is a valuable choice in the management of thoracic disc
      herniation.

PMID- 22964012
TI  - A biomechanical evaluation of a spacer with integrated plate for treating
      adjacent-level disease in the subaxial cervical spine.
AB  - BACKGROUND CONTEXT: Adjacent level degeneration (ALD) has been reported as one of
      the long-term consequences of anterior discectomy and fusion despite its clinical
      success in treating cervical pathologies. Traditionally, ALD is treated by
      replacing the previously implanted plate with a longer plate, which can lead to
      postoperative complications. The biomechanics of SIP in the adjacent level has
      not been investigated. PURPOSE: To evaluate the multidirectional stability of a
      spacer with integrated plate (SIP) in comparison to a traditional spacer and
      plate (TSP). STUDY DESIGN: To evaluate the biomechanical stability of a spacer
      with integrated plate adjacent to a traditional spacer and plate construct in a
      human cervical cadaveric model. METHODS: Eight fresh human cervical (C2-C7)
      cadaver spines were mounted on a six degree-of-freedom spine simulator. The
      sequence of test constructs was: 1) Intact; 2) TSP (C4-C6) with SIP (C3-C4); and
      3) TSP (C3-C6). An unconstrained moment of +/-1.5 Nm was used in flexion
      extension, lateral bending, and axial rotation. Range of motion (ROM) was
      measured by a digital motion analysis system. Statistical analysis was performed
      using ANOVA repeated measures. RESULTS: All instrumented constructs significantly
      reduced ROM compared to the intact condition. No statistically significant
      difference was observed between the two-level TSP with an adjacent SIP construct
      and three-level TSP construct in all loading modes. CONCLUSION: The biomechanical
      study shows that adding a spacer with integrated plate adjacent to a two-level
      anterior plate demonstrates equivalent stability to a three-level anterior plate.
      The spacer with integrated plate, which preserves the originally plated fusion
      levels, may overcome the complications associated with the traditional technique
      of replacing the original plate with a longer plate. However, prospective
      clinical studies are required to address the clinical benefits and challenges, if
      any.

PMID- 22964013
TI  - An investigation into PEEK-on-PEEK as a bearing surface candidate for cervical
      total disc replacement.
AB  - BACKGROUND CONTEXT: Total disc replacement (TDR) is a relatively new
      reconstructive non-fusion technology for the spine that aims to overcome some of
      the limitations of fusion technology. The first generation artificial discs were
      mainly based on well-known material combinations from total hip replacement.
      PURPOSE: To evaluate the feasibility of PEEK-on-PEEK as a bearing surface
      material for use in cervical TDR. STUDY DESIGN: In vitro biotribological study
      including the assessment of different parameters, including the influence of
      radial clearance, axial load, and angular motion on the wear performance of a
      PEEK-on-PEEK bearing. METHODS: PEEK-on-PEEK bearing couples with ball-and-socket
      articulation were prepared using standard production methods. Two groups of
      bearing couples, one with large radial clearances and the other with small radial
      clearances, were manufactured for testing. Wear tests were performed using a
      servo-hydraulic wear simulator that allowed controlled motions to be applied in
      three axes corresponding to flexion-extension, lateral bending, and axial
      rotation. In addition, a dynamic axial compressive load was applied to simulate
      the weight of the head. All tests were performed at 37 degrees C (+/-2 degrees C)
      in bovine calf serum with a 30 g/l protein concentration. In the first test
      series, the influence of the radial clearance on the wear behavior was evaluated
      using the load and motion parameters for cervical TDR as defined in the ISO
      standard 18192-1. Subsequent tests were performed to check if surface degradation
      was influenced by thermal effects. Finally, in a third series of tests, the
      effect of load and motion profiles on wear performance was investigated by
      applying increased loads and corresponding motion parameters for lumbar TDR as
      defined in the ISO standard 18192-1. RESULTS: The measured wear rates for a PEEK
      on-PEEK bearing under cervical test conditions were considerably larger than
      those of similar testing using UHMWPE-on-CoCr and seemed to depend on initial
      radial clearances. The PEEK bearing surfaces exhibited severe surface degradation
      for large and small clearances, but the group with smaller clearances seemed to
      have less severe damage. Thermal effects were not found to play a role in the
      surface degradation, as the temperature near the bearing surface was measured and
      found to vary only a few degrees during testing. A change of the wear test
      parameters to simulate lumbar loading resulted in a considerable wear rate
      reduction as well as in the preservation of the bearing surfaces. CONCLUSIONS: It
      was found that a cervical TDR using a PEEK-on-PEEK bearing may be subjected to
      severe long-term degradation of the bearing surfaces. In this study, the use of
      PEEK as an articulation material for cervical TDR was found to be sensitive to
      loading conditions as well as to the initial clearance of the bearing surfaces.
      Despite the excellent properties of PEEK as an implant material, its use for
      articulating surfaces for cervical TDR must be critically reviewed.

PMID- 22964014
TI  - A new classification for complex lumbosacral injuries.
AB  - BACKGROUND CONTEXT: The optimal classification and treatment algorithm for
      complex lumbosacral injuries, in particular high-energy sacral fractures and
      lumbosacral dissociation (LSD) injuries, remains controversial. Currently used
      classification systems are largely descriptive, lacking validity,
      reproducibility, treatment considerations, and prognostic information. PURPOSE:
      We set out to develop a comprehensive, yet practical, classification system for
      complex lumbosacral injuries that assists in clinical decision making. STUDY
      DESIGN: We developed a new classification system for complex lumbosacral injuries
      derived through literature review, expert opinion, and our clinical experience
      treating combat casualties over the past 10 years. We have seen an increased
      incidence of complex sacral fractures and LSD injuries after high-energy blast
      trauma, motor vehicle collisions, and aircraft crashes. METHODS: We performed an
      extensive literature review and discussed the proposed classification with spinal
      trauma surgeons from a variety of institutions familiar with the treatment of
      complex high-energy sacral fractures and LSD injuries. We identified the
      significant clinical and radiographic variables encountered in the decision
      making process for the treatment of complex lumbosacral injuries. Existing
      classification systems were reviewed in light of these essential characteristics,
      and their limitations were defined and addressed with the new system. RESULTS: A
      new classification system called lumbosacral injury classification system (LSICS)
      was devised based on three injury characteristics: injury morphology, posterior
      ligamentous complex integrity, and neurologic status. A composite injury severity
      score was calculated by summing a weighted score from each category, allowing
      patients to be stratified into surgical and nonsurgical treatment groups based on
      threshold values. Modifiers to determining appropriate selection for operative
      treatment include systemic injury load and physiological status of the
      polytraumatized patient, soft-tissue status, and expected time to mobility.
      Finally, an algorithm was developed to determine the optimum operative technique
      based on the previously outlined injury characteristics. CONCLUSIONS: The LSICS
      provides a comprehensive and practical approach for evaluating injury severity
      and guiding clinical decision making. This system provides common language for
      surgeons to communicate various injury patterns and formulate treatment
      modalities. Further studies are necessary to determine the reliability and
      validity of this new classification system.

PMID- 22964015
TI  - Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in
      patients with myelodysplastic syndromes: an ex-vivo study.
AB  - BACKGROUND: Arsenic Trioxide (ATO) is effective in about 20% of patients with
      myelodysplasia (MDS); its mechanisms of action have already been evaluated in
      vitro, but the in vivo activity is still not fully understood. Since ATO induces
      apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in
      patients' bone marrow before and after ATO treatment. For this analysis, we
      selected 12 patients affected by MDS who received ATO in combination with
      Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT
      Number 2005-001321-28. METHODS: Real-time PCR quantitative assays for genes
      involved in apoptosis were performed using TaqMan(r) Assays in 384-Well
      Microfluidic Cards "TaqMan(r) Human Apoptosis Array".Quantitative RT-PCR for
      expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct)
      were normalized to the median expression of 3 housekeeping genes present in the
      card (18S, ACTB and GAPDH). RESULTS: ATO treatment induced up-regulation of some
      pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and
      down-regulation of ICEBERG. In the majority of cases with stable disease,
      apoptotic gene expression profile did not change, whereas in cases with advanced
      MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved
      a major response: in the patient with refractory anemia the treatment down
      regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes
      were up-regulated in the patient affected by refractory anemia with excess of
      blasts-1. Responsive patients showed a higher induction of BAD than those with
      stable disease. Finally, WT1 gene expression was down-regulated by the treatment
      in responsive cases. CONCLUSIONS: These results represent the basis for a
      possible association of ATO with other biological compounds able to modify the
      apoptotic pathways, such as inhibitors of the BCL2 family.

PMID- 22964016
TI  - In situ UV-VIS-NIR absorbing properties of atmospheric aerosol particles:
      estimates of the imaginary refractive index and comparison with columnar values.
AB  - In this work, a novel technique is used to estimate the aerosol complex index of
      refraction of in situ collected samples. Samples of atmospheric particulate
      matter were collected in El Arenosillo, southern Spain, on polycarbonate filters
      during summer 2004 as part of an aerosol characterization campaign. These samples
      were analyzed for the volumetric absorption coefficient in the 320-800 nm
      spectral region and an estimation of the effective imaginary refractive index was
      made. The values of the imaginary part of the complex refractive index ranged
      between 0.0009-0.0215 at 800 nm and 0.0015-0.0114 at 320 nm. Little dependence on
      the wavelength was observed. Several intense and long lasting desert outbreaks
      were registered during the campaign and the complex refractive index almost
      doubles its value during these dust events. Finally, we present a comparison of
      data obtained in situ with columnar data obtained from the AERONET network. A
      correlation factor of 0.64 was obtained between both data, which gives an idea of
      how accurately the in situ ground data represent the total column.

PMID- 22964017
TI  - Phasic bursting pattern of postural responses may reflect internal dynamics:
      simulation of trunk reflexes with a neural oscillator model.
AB  - Postural responses are usually investigated as reflexes. Several trials are
      averaged, and trial-to-trial variations are interpreted as noise. Several studies
      providing single-trial data plots revealed oscillations that may be cancelled out
      in averaged time series. Variations between single trials may also be interpreted
      as a consequence of changed dynamic properties of the neural circuitries.
      Therefore, we propose a Matsuoka oscillator model to describe single-trial
      postural responses to external perturbations. The applicability of the model was
      demonstrated by a comparison between simulations and experimental
      electromyographic (EMG) data. Vertical force perturbations of durations 0.4 s and
      0.2 s were applied via a handle to 10 subjects. Handle force was used as model
      input, and EMG data from the external oblique muscles was compared with
      simulation output. Model coefficients were optimized by a least-squares
      algorithm. The optimization produced a good similarity between simulation and
      experimental data with determination coefficients of r(2)=0.7 and greater.
      Furthermore, as a model validation, the model coefficients were used to predict
      other perturbation trials with similarities between predictions and respective
      EMG data of about r(2)=0.45, which was in the range of trial-to-trial EMG
      variability. The observed oscillations are assumed to originate from the central
      nervous system with changes in the neural circuitries between trials. Hence, the
      oscillations in single trial responses which are usually regarded as noise might
      be generated by the dynamics of a neural oscillator.

PMID- 22964018
TI  - The inaccuracy of surface-measured model-derived tibiofemoral kinematics.
AB  - This study assessed the accuracy of surface-measured OpenSim-derived tibiofemoral
      kinematics in functional activities. Ten subjects with unilateral, isolated grade
      II PCL deficiency performed level running and stair ascent. A dynamic stereo
      radiography (DSX) system and a Vicon motion capture system simultaneously
      measured their knee or lower extremity movement. Surface marker motion data from
      the Vicon system were used to create subject-specific models in OpenSim and
      derive the tibiofemoral kinematics. The surface-measured model-derived
      tibiofemoral kinematics in all six degrees of freedom (DOFs) were then compared
      with those measured by the DSX as the benchmarks. The differences between surface
      and DSX-measured tibiofemoral kinematics were found to be substantial: the
      overall mean (+/-SD) RMS differences during running were 9.1+/-3.2 degrees ,
      2.0+/-1.2 degrees , and 6.4+/-4.5 degrees  for the flexion-extension, abduction
      adduction, and internal-external rotations, respectively, and 7.1+/-3.2 mm, 8.8+/
      3.7 mm, and 1.9+/-1.2 mm for anterior-posterior, proximal-distal, and medial
      lateral translations, respectively. The differences were more pronounced in
      relatively higher speed running than in stair ascent. It was also found that
      surface-based measures significantly underestimated the mean as well as inter
      subject variability of the differences between PCL-injured and intact knees in
      abduction-adduction, internal-external rotations, and anterior-posterior
      translation.

PMID- 22964019
TI  - Influence of chondrocyte maturation on acute response to impact injury in PEG
      hydrogels.
AB  - Age is a risk factor in developing osteoarthritis, but the link is not well
      understood. It is thought that age predisposes the tissue to osteoarthritis when
      other risk factors are involved, e.g. abnormal biomechanics. Therefore, this
      study aimed to test the hypothesis that chondrocyte response to injurious loading
      is dependent on donor age. Bovine chondrocytes were selected as model cells and
      isolated from skeletally immature (juvenile, 1-3 weeks) or mature (adult, 2-3
      years) cartilage to represent different aged donors. Juvenile and adult
      chondrocytes were encapsulated in identical 3D poly(ethylene glycol) hydrogels
      and subjected to an initial compressive impact load of 25.6+/-7.5 kN/m(2) applied
      to 50% strain. Under free swelling culture, adult chondrocytes exhibited higher
      intracellular ROS levels and catabolism, specifically collagen degradation, when
      compared to juvenile chondrocytes. In response to injurious load, adult
      chondrocytes responded with higher cell death, while juvenile chondrocytes
      responded with greater apoptosis and greater increases in intracellular ROS. With
      respect to anabolism and catabolism in response to injurious load, adult
      chondrocytes exhibited decreased aggrecan and collagen deposition, while juvenile
      chondrocytes exhibited decreased proteoglycan synthesis and increased collagen
      degradation. Overall, chondrocytes responded to injury regardless of age, but
      exhibited age-dependent responses with respect to anabolism and catabolism. These
      findings confirm that age influences how chondrocytes respond to abnormal
      biomechanical cues, warranting further study into the mechanisms of how cells,
      age, and injury contribute to the onset of osteoarthritis.

PMID- 22964020
TI  - Missing data and imputation: a practical illustration in a prognostic study on
      low back pain.
AB  - OBJECTIVE: When designing prediction models by complete case analysis (CCA),
      missing information in either baseline (predictors) or outcomes may lead to
      biased results. Multiple imputation (MI) has been shown to be suitable for
      obtaining unbiased results. This study provides researchers with an empirical
      illustration of the use of MI in a data set on low back pain, by comparing MI
      with the more commonly used CCA. Effects will be shown of imputing missing
      information on the composition and performance of prognostic models,
      distinguishing imputation of missing values in baseline characteristics and
      outcome data. METHODS: Data came from the Beliefs about Backpain cohort, a study
      of psychologic obstacles to recovery in primary care back pain patients in the
      United Kingdom. Candidate predictors included demographics, back pain
      characteristics, and psychologic variables. Complete case analysis was compared
      with MI within patients with complete outcome but missing baseline data (n=809)
      and patients with missing baseline or outcome data (n=1591). Multiple imputation
      was performed by a Multiple Imputation by Chained Equations procedure. RESULTS:
      Cases with missing outcome data (n=782, 49.1%) or with missing baseline data
      (n=116, 8%) both differed from complete cases regarding the distribution of some
      predictors and more often had a poor outcome. When comparing CCA with MI, model
      composition showed to be affected. CONCLUSIONS: Complete case analysis can give
      biased results, even when only small amounts of data are missing. Now that MI is
      available in standard statistical software, we recommend that it be used to
      handle missing data.

PMID- 22964021
TI  - Radiographic analysis of the anterior to posterior open mouth (APOM) cervical
      spine view: frequency of atlas transverse process overlap of the inferior tip of
      the mastoid process.
AB  - OBJECTIVE: The purpose of this study was to measure the frequency with which the
      atlas transverse process is overlapped by the inferior tip of the mastoid process
      based upon radiographic analysis of the anterior to posterior open mouth (APOM)
      cervical spine view. METHODS: This is a retrospective study. Anterior to
      posterior open mouth radiographs (N = 120) were obtained from patient files at a
      chiropractic clinic. Dimensions were bilaterally measured: the vertical distance
      from the inferior mastoid to the superior margin of the C1 transverse process
      (C1TP) and the vertical distance from the inferior mastoid to the inferior margin
      of the C1TP. The percentage of the C1TP occluded by the mastoid process was
      calculated by determining the occlusal distance. These percentages were grouped
      into 4 categories: no occlusion, 1% to 50%, 50% to 99%, and 100%. RESULTS: The
      occlusal distance for the left and right ranged from -7.1 to 19.0 mm and -7.5 to
      19.5 mm, respectively. The mean occlusal distance was identical on the left and
      right sides (4.6 [SD, 5.1 mm] and 4.7 mm [SD, 5.0 mm], respectively). The
      percentage of occlusion for the left and right transverse processes ranged from
      0% to 80% and 0% to 100%, respectively. The mean percentage was 6.4% (SD, 16.4)
      on the left and 6.2% (SD, 16.3) on the right. CONCLUSION: This study shows that
      the occlusal distance for the left and right ranged from -7.1 to 19.0 mm and -7.5
      to 19.5 mm, respectively. A total occlusion of the C1TP occurred in 1 side of 120
      participants in this sample.

PMID- 22964022
TI  - Angiotensin II-induced pro-fibrotic effects require p38MAPK activity and
      transforming growth factor beta 1 expression in skeletal muscle cells.
AB  - Fibrotic disorders are typically characterised by excessive connective tissue and
      extracellular matrix (ECM) deposition that preclude the normal healing of
      different tissues. Several skeletal muscle dystrophies are characterised by
      extensive fibrosis. Among the factors involved in skeletal muscle fibrosis is
      angiotensin II (Ang-II), a key protein of the renin-angiotensin system (RAS). We
      previously demonstrated that myoblasts responded to Ang-II by increasing the ECM
      protein levels mediated by AT-1 receptors, implicating an Ang-II-induced reactive
      oxygen species (ROS) by a NAD(P)H oxidase-dependent mechanism. In this paper, we
      show that in myoblasts, Ang-II induced the increase of transforming growth factor
      beta 1 (TGF-beta1) and connective tissue growth factor (CTGF) expression through
      its AT-1 receptor. This effect is dependent of the NAD(P)H oxidase (NOX)-induced
      ROS, as indicated by a decrease of the expression of both pro-fibrotic factors
      when the ROS production was inhibited via the NOX inhibitor apocynin. The
      increase in pro-fibrotic factors levels was paralleled by enhanced p38MAPK and
      ERK1/2 phosphorylation in response to Ang-II. However, only the p38MAPK activity
      was critical for the Ang-II-induced fibrotic effects, as indicated by the
      decrease in the Ang-II-induced TGF-beta1 and CTGF expression and fibronectin
      levels by SB-203580, an inhibitor of the p38MAPK, but not by U0126, an inhibitor
      of ERK1/2 phosphorylation. Furthermore, we showed that the Ang-II-dependent
      p38MAPK activation, but not the ERK1/2 phosphorylation, was necessary for the NOX
      derived ROS. In addition, we demonstrated that TGF-beta1 expression was required
      for the Ang-II-induced pro-fibrotic effects evaluated by using SB-431542, an
      inhibitor of TGF-betaRI kinase activity, and by knocking down TGF-beta1 levels by
      shRNA technique. These results strongly suggest that the fibrotic response to Ang
      II is mediated by the AT-1 receptor and requires the p38MAPK phosphorylation, NOX
      induced ROS, and TGF-beta1 expression increase mediated by Ang-II in skeletal
      muscle cells.

PMID- 22964023
TI  - MiRNA expression analysis of cancer-associated fibroblasts and normal fibroblasts
      in breast cancer.
AB  - Cancer-associated fibroblasts (CAFs) promote tumorigenesis, growth, invasion and
      metastasis of cancer, whereas normal fibroblasts (NFs) are thought to suppress
      tumor progression. Little is known about miRNAs expression differences between
      CAFs and NFs or the patient-to-patient variability in miRNAs expression in breast
      cancer. We established primary cultures of CAFs and paired NFs from six resected
      breast tumor tissues that had not previously received radiotherapy or
      chemotherapy treatment and analyzed with miRNAs microarrays. The array data were
      analyzed using paired SAM t-test and filtered according to alpha and q values.
      Pathway analysis was conducted using DAVID v6.7. We identified 11 dysregulated
      miRNAs in CAFs: three were up-regulated (miR-221-5p, miR-31-3p, miR-221-3p),
      while eight were down-regulated (miR-205, miR-200b, miR-200c, miR-141, miR-101,
      miR-342-3p, let-7g, miR-26b). Their target genes are known to affect cell
      differentiation, adhesion, migration, proliferation, secretion and cell-cell
      interaction. By our knowledge it is firstly identify the expression profiles of
      miRNAs between CAFs and NFs and revealed their regulation on the associated
      signaling pathways.

PMID- 22964024
TI  - Zinc fingers of the cerebellum (Zic): transcription factors and co-factors.
AB  - The Zic genes encode zinc finger containing proteins that can bind proteins and
      DNA. The understanding of Zic molecular networks has been hampered by functional
      redundancy amongst family members, and because their loss-of-function phenotypes
      are indicative of a role in many signalling pathways. Recently molecular evidence
      has emerged confirming the pleiotropic nature of these proteins: they act both as
      classical transcription factors and as co-factors to directly and indirectly
      influence gene expression. It has long been known that germ-line mutation of the
      Zic genes in human and mouse causes a range of congenital disorders. Recently
      connections between Zic proteins and stem cell function have also emerged
      suggesting a role in adult onset diseases. The immediate challenge is to
      determine when and where these proteins act as transcription factors/co-factors
      during development and disease and how the switch between these roles is
      controlled.

PMID- 22964025
TI  - Androgen-responsive and nonresponsive prostate cancer cells present a distinct
      glycolytic metabolism profile.
AB  - Prostate cancer (PCa) progresses from an early stage, confined to prostate, to a
      more aggressive metastasized cancer related with loss of androgen responsiveness.
      Although, it has been recognized that PCa cells have unique metabolic features,
      their glycolytic profile in androgen-dependent and androgen-independent stages of
      disease is much less known. Hence, the main purpose of this study was to compare
      glucose metabolism in androgen-responsive (LNCaP) and androgen-nonresponsive
      (PC3) PCa cells. Cell culture medium was collected and differences in glucose
      consumption and, lactate and alanine production were measured using Proton
      Nuclear Magnetic Resonance ((1)H NMR) spectra analysis. The mRNA and protein
      expression of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1
      (PFK1), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) were
      determined by real-time PCR and Western Blot, respectively. The obtained results
      demonstrate that androgen-responsive (LNCaP) and androgen-nonresponsive (PC3)
      cells consumed similar amounts of glucose, whereas PC3 cells present higher
      lactate production. This increase in lactate production was concomitant with
      higher levels of MCT4 protein, increased LDH activity and higher lactate/alanine
      ratio, also suggesting increased levels of oxidative stress in PC3 cells.
      However, protein levels of LDH, associated with lactate metabolism, and GLUT3,
      involved in glucose uptake, were decreased in PC3 comparatively with LNCaP.
      Androgen-responsive and nonresponsive PCa cells present distinct glycolytic
      metabolism profiles, which suggest that targeting LDH and MCT4 metabolic pathways
      may be an important step for the development of new diagnostic and therapeutic
      strategies in the different stages of PCa.

PMID- 22964026
TI  - PRO-PACT: retrospective observational study on the prophylactic use of
      recombinant factor VIIa in hemophilia patients with inhibitors.
AB  - INTRODUCTION: Hemophilia patients with inhibitors have frequent bleeding episodes
      and often develop hemophilic arthropathy which is in contradistinction to non
      inhibitor patients for whom prophylaxis prevents joint disease. Recently, two
      prospective trials have demonstrated that secondary prophylaxis with bypassing
      agents in inhibitor patients offers benefit by reducing bleeding episodes. This
      report describes the clinical experience of secondary prophylaxis in a large
      population of inhibitor patients. PATIENTS/METHODS: This retrospective,
      observational study was performed by abstracting data from medical records of
      patients in whom secondary prophylaxis with rFVIIa was prescribed. Data were
      collected by professional medical record abstractors and included patient
      demographics, dosing regimens, bleeding events, and healthcare resource
      utilization. Data analysis was descriptive and included sensitivity analyses.
      RESULTS: Data from 86 patients from 14 countries were collected. The primary
      outcome measure (% reduction in bleeding) was 46% (95% CI, -54.0 to -38.2) in
      patients with at least one bleeding episodes prior to starting prophylaxis and
      52% (95% CI, -60.7 to -43.3) in patients with at least one bleeding episode per
      month prior to starting prophylaxis. A variety of subanalyses were performed,
      including among age and bleed location; the results for pediatric patients,
      adults, target and non-target joint bleeds categorizations were similar to the
      overall primary outcome. CONCLUSIONS: The results in this large observational
      study are similar to those from the previously reported prospective study of
      prophylaxis with rFVIIa in inhibitor positive patients, although this study
      represents a more typical inhibitor population who utilized prophylaxis in the
      clinical setting. As such, prophylaxis should be considered a potentially
      effective therapy in hemophilia patients with inhibitors.

PMID- 22964027
TI  - Effect of laminar shear stress on the distribution of Weibel-Palade bodies in
      endothelial cells.
AB  - BACKGROUND: Vascular endothelial cells (ECs) provide a highly interactive barrier
      between blood and the underlying tissues. It is well established that ECs exposed
      to laminar flow align in the direction of flow and also arrange their actin
      stress fibers in a parallel manner in the direction of flow. Also the
      organization of the microtubule network is altered in response to flow with
      repositioning of the microtubule-organizing centre (MTOC) in the direction of
      flow. Weibel-Palade bodies (WPBs) are endothelial cell specific storage
      organelles that contain a number of important homeostatic and inflammatory
      components. Dynamics of WPBs are controlled by microtubules and the actin
      cytoskeleton. OBJECTIVES: Here, we monitored flow-induced changes in distribution
      of WPBs. METHODS: ECs were exposed for five days to laminar shear stress of 10
      dyne/cm(2). Subsequently we measured the distance of individual WPBs with respect
      to the centre of the nucleus using Image Pro Plus. RESULTS: ECs aligned in the
      direction of flow under these conditions. After 5 days the MTOC was positioned
      downstream of the nucleus in the direction of the flow. The number of WPBs per
      cell was slightly reduced as a result of the application of flow. Unexpectedly,
      only minor differences in the distribution of WPBs in ECs cultured under laminar
      flow were observed when compared to that of cells grown under static conditions.
      CONCLUSIONS: Our findings suggest that laminar flow does not induce major changes
      in number and distribution of WPBs in ECs.

PMID- 22964028
TI  - A meta-analysis of the efficacy of anodal transcranial direct current stimulation
      for upper limb motor recovery in stroke survivors.
AB  - STUDY DESIGN: Systematic review and meta-analysis. INTRODUCTION: Prior reviews on
      the effects of anodal transcranial direct current stimulation (a-tDCS) have shown
      the effectiveness of a-tDCS on corticomotor excitability and motor function in
      healthy individuals but nonsignificant effect in subjects with stroke. PURPOSE:
      To summarize and evaluate the evidence for the efficacy of a-tDCS in the
      treatment of upper limb motor impairment after stroke. METHODS: A meta-analysis
      of randomized controlled trials that compared a-tDCS with placebo and change from
      baseline. RESULTS: A pooled analysis showed a significant increase in scores in
      favor of a-tDCS (standard mean difference [SMD]=0.40, 95% confidence interval
      [CI]=0.10-0.70, p=0.010, compared with baseline). A similar effect was observed
      between a-tDCS and sham (SMD=0.49, 95% CI=0.18-0.81, p=0.005). CONCLUSION: This
      meta-analysis of eight randomized placebo-controlled trials provides further
      evidence that a-tDCS may benefit motor function of the paretic upper limb in
      patients suffering from chronic stroke. LEVEL OF EVIDENCE: Level 1a.

PMID- 22964029
TI  - Advances in video game methods and reporting practices (but still room for
      improvement): a commentary on Strobach, Frensch, and Schubert (2012).
AB  - Strobach, Frensch, and Schubert (2012) presented evidence that action video game
      experience improves task-switching and reduces dual-task costs. Their design
      commendably adhered to many of the guidelines proposed by Boot, Blakely and
      Simons (2011) to overcome common method and interpretation problems in this
      literature. Adherence to these method guidelines is necessary in order to reduce
      the influence of demand characteristics, placebo effects, and underreporting that
      might otherwise produce false positive findings. In their paper, Strobach et al.
      (2012) appear to have misinterpreted some of these proposed guidelines, meaning
      that their methods did not eliminate possible sources of demand characteristics
      and differential placebo effects. At this important, early stage of video game
      research, reducing the likelihood of false positive findings is essential. In
      this commentary we clarify our methodological critiques and guidelines, identify
      ways in which this new study did and did not meet these guidelines, and discuss
      how these methodological issues should constrain the interpretation of the
      reported evidence.

PMID- 22964030
TI  - Characterization and relative sonocatalytic efficiencies of a new MWCNT and CdS
      modified TiO2 catalysts and their application in the sonocatalytic degradation of
      rhodamine B.
AB  - TiO(2) nanoparticles modified with MWCNTs and CdS were synthesized by the sol-gel
      method followed by solvothermal treatment at low temperature. The chemical
      composition and surface structure of the CdS/CNT-TiO(2) composites were
      investigated by X-ray diffraction, specific surface area measurements, energy
      dispersive X-ray spectroscopy, transmission electron microscopy, and scanning
      electron microscopy. Then a series of sonocatalytic degradation experiments were
      carried out under ultrasonic irradiation in the presence of CNT/TiO(2) and the
      CdS/CNT-TiO(2) composites. It was found that RhB was quickly and effectively
      degraded under different ultrasonic conditions. As expected, the nanosized
      CdS/CNT-TiO(2) photocatalyst showed enhanced activity compared with the non CdS
      treated CNT/TiO(2) material in the sonocatalytic degradation of RhB. The
      sonocatalyst CCTb with 34.68% contents of Ti heat treated at 500  degrees C for
      1h showed the highest sonocatalytic activity. The synergistic effect of the
      greater surface area and catalytic activities of the composite catalysts was
      examined in terms of their strong adsorption ability and interphase interaction
      by comparing the effects of different amounts of MWCNTs and CdS in the catalysts
      and their roles. The mechanism of sonocatalytic degradation over the CdS/CNT
      modified TiO(2) composites under different ultrasonic conditions was also
      discussed.

PMID- 22964031
TI  - Optimization of ultrasonic-assisted extraction of pomegranate (Punica granatum
      L.) seed oil.
AB  - The effectiveness of ultrasonic-assisted extraction (UAE) of pomegranate seed oil
      (PSO) was evaluated using a variety of solvents. Petroleum ether was the most
      effective for oil extraction, followed by n-hexane, ethyl acetate, diethyl ether,
      acetone, and isopropanol. Several variables, such as ultrasonic power, extraction
      temperature, extraction time, and the ratio of solvent volume and seed weight
      (S/S ratio) were studied for optimization using response surface methodology
      (RSM). The highest oil yield, 25.11% (w/w), was obtained using petroleum ether
      under optimal conditions for ultrasonic power, extraction temperature, extraction
      time, and S/S ratio at 140 W, 40  degrees C, 36 min, and 10 ml/g, respectively.
      The PSO yield extracted by UAE was significantly higher than by using Soxhlet
      extraction (SE; 20.50%) and supercriti cal fluid extraction (SFE; 15.72%). The
      fatty acid compositions were significantly different among the PSO extracted by
      Soxhlet extraction, SFE, and UAE, with punicic acid (>65%) being the most
      dominant using UAE.

PMID- 22964032
TI  - Optimization of olive leaf extract obtained by ultrasound-assisted extraction
      with response surface methodology.
AB  - In the present article, ultrasound-assisted extraction (UAE) of polyphenols from
      agricultural and industrial waste of olive oil and table oil productions, olive
      tree (Olea europaea) leaves were investigated. The aim of the study is to examine
      the extraction parameters such as solvent concentration (0-100% ethanol (EtOH),
      v/v), the ratio of solid to solvent (25-50mg/mL) and extraction time (20-60 min),
      and to obtain the best possible combinations of these parameters through response
      surface methodology (RSM). The extract yield was stated as mg extract per g of
      dried leaf (DL). Total phenolic content was expressed in gallic acid equivalent
      (GAE) per g of dried leaf. Free radical scavenging activity for the antioxidant
      capacity was tested by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The second
      order polynomial model gave a satisfactory description of the experimental data.
      201.2158 mg extract/g DL, 25.0626 mg GAE/g DL, and 95.5610% in respect to
      inhibition of DPPH radical were predicted at the optimum operating conditions
      (500 mg solid to 10 mL solvent ratio, 60 min of extraction time and 50% EtOH
      composition), respectively.

PMID- 22964033
TI  - Testicular vascular cone development and its association with scrotal
      temperature, semen quality, and sperm production in beef bulls.
AB  - The objectives of this study were to characterize development of the testicular
      vascular cone using ultrasonography and to determine associations of vascular
      cone morphology with scrotal temperature, semen quality, and sperm production.
      Beef bulls (n=70) were examined from 10 to 70 wk of age in two years, and a third
      group of bulls (n=44) was examined only at 74 wk of age. Testicular vascular cone
      diameter increased until approximately 13.5 mo of age, or until 1 to 8 wk before
      maximum scrotal circumference was observed. Vascular cone fat thickness also
      increased with age and followed a pattern similar to that observed for backfat.
      Testicular artery wall thickness and the distance from the arterial to the venous
      blood in the vascular cone decreased with proximity to the testis. Vascular cone
      diameter was negatively correlated with scrotal surface temperatures and with the
      percentage of sperm head defects and detached sperm heads, but positively
      correlated with the percentage of normal sperm. The arterial-venous blood
      distance was negatively correlated with the percentage of normal sperm and
      positively correlated with percentage of sperm head defects and proximal
      droplets. In conclusion, testicular vascular cone diameter increased with age
      following testicular development, whereas vascular cone fat thickness increased
      similar to a pattern observed for backfat. Increased testicular vascular cone
      diameter and decreased distance between arterial and venous blood were associated
      with increased percentage of normal sperm and decreased percentages of sperm
      defects.

PMID- 22964034
TI  - Individual variation related to testicular biometry and semen characteristics in
      collared peccaries (Tayassu Tajacu Linnaeus, 1758).
AB  - The aim of this research was to study the individual variation with regard to the
      morphometry of the testes evaluated by ultrasonography and semen characteristics
      and to verify the existence of relationship between these variables in collared
      peccaries. In addition, the testes of the animals were evaluated by histology in
      order to determine the proportion occupied by the seminiferous tubules. A total
      of 52 ejaculates were obtained from ten adult specimens that had been restrained
      by anesthesia. The testicular measurements (length, height, and width) were
      performed by ultrasonography, and the testicular volume was calculated according
      to Lambert's formula. The scrotal circumference was measured by encircling the
      thickest portion of the testicle with a graduated nylon tape. The semen was
      collected by electroejaculation. Testicular fragments were analyzed through
      classic histology for the determination of the area occupied by the seminiferous
      tubules. The results show a great amount of individual variation with regard to
      testicular morphometry and semen characteristics. No significant correlations
      were obtained between testicular measurements and semen characteristics. The
      histometric analysis revealed that 67.8% of the testes are occupied by
      seminiferous tubules. Results show that the measurement of testicular dimensions
      does not serve as an indicator of the quality of semen obtained by
      electroejaculation in collared peccaries, as there is no correlation between
      testicular morphometry and semen characteristics in this species that presents
      large variations among individuals.

PMID- 22964036
TI  - Preparation of highly regioselective amphiprotic chitosan derivative via "click
      chemistry".
AB  - Synthesis of a highly regioselective amphiprotic chitosan derivative was achieved
      by click chemistry. The Huisgen cycloaddition between 6-azido-6-deoxy-N-pthaloyl
      chitosan and methyl propiolate was successfully carried out in the presence of
      Cu(I) catalyst. After the reaction, both the phthaloyl protecting group and
      methyl group were completely removed by hydrazine. FT-IR and NMR spectroscopy as
      well as elemental analysis strongly support the structural uniformity of the
      desired amphiprotic chitosan derivative, which has both a carboxylic group with a
      1,4-triazole linker at the C-6 position and an amino group at the C-2 position
      per repeating unit. The amphiprotic chitosan derivative was soluble under both
      acidic and basic aqueous conditions. In contrast, it formed nanoparticle under
      neutral condition due to the interaction between the positive (-NH(3)(+)) and
      negative (-COO(-)) ions on the chitosan derivative.

PMID- 22964035
TI  - Increased expression of CD133 and reduced dystroglycan expression are strong
      predictors of poor outcome in colon cancer patients.
AB  - BACKGROUND: Expression levels of CD133, a cancer stem cell marker, and of the
      alpha-subunit of the dystroglycan (alpha-DG) complex, have been previously
      reported to be altered in colorectal cancers. METHODS: Expression levels of CD133
      and alpha-DG were assessed by immunohistochemistry in a series of colon cancers
      and their prognostic significance was evaluated. RESULTS: Scattered cells
      positive for CD133 were rarely detected at the bases of the crypts in normal
      colonic mucosa while in cancer cells the median percentage of positive cells was
      5% (range 0-80). A significant correlation was observed with pT parameter and
      tumor stage but not with tumor grade and N status. Recurrence and death from
      disease were significantly more frequent in CD133-high expressing tumors and
      Kaplan-Meier curves showed a significant separation between high vs low expressor
      groups for both disease-free (p = 0.002) and overall (p = 0.008)
      survival.Expression of alpha-DG was reduced in a significant fraction of tumors
      but low alpha-DG staining did not correlate with any of the classical clinical
      pathological parameters. Recurrence and death from the disease were significantly
      more frequent in alpha-DG-low expressing tumors and Kaplan-Meier curves showed a
      significant separation between high vs low expressor tumors for both disease-free
      (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but
      not loss of alpha-DG, confirmed to be an independent prognostic parameters at a
      multivariate analysis associated with an increased risk of recurrence (RR = 2.4;
      p = 0.002) and death (RR = 2.3; p = 0.003). CONCLUSIONS: Loss of alpha-DG and
      increased CD133 expression are frequent events in human colon cancer and
      evaluation of CD133 expression could help to identify high-risk colon cancer
      patients.

PMID- 22964037
TI  - D(1)-like receptors in the nucleus accumbens shell regulate the expression of
      contextual fear conditioning and activity of the anterior cingulate cortex in
      rats.
AB  - Although dopamine-related circuits are best known for their roles in appetitive
      motivation, consistent data have implicated this catecholamine in some forms of
      response to stressful situations. In fact, projection areas of the ventral
      tegmental area, such as the amygdala and hippocampus, are well established to be
      involved in the acquisition and expression of fear conditioning, while less is
      known about the role of the medial prefrontal cortex (mPFC) and nucleus accumbens
      (NAc) in these processes. In the present study, we initially investigated the
      involvement of the mPFC and NAc in the expression of conditioned fear, assessing
      freezing behaviour and Fos protein expression in the brains of rats exposed to a
      context, light or tone previously paired with footshocks. Contextual and cued
      stimuli were able to increase the time of the freezing response while only the
      contextual fear promoted a significant increase in Fos protein expression in the
      mPFC and caudal NAc. We then examined the effects of specific dopaminergic
      agonists and antagonists injected bilaterally into the posterior medioventral
      shell subregion of the NAc (NAcSh) on the expression of contextual fear.
      SKF38393, quinpirole and sulpiride induced no behavioural changes, but the D1
      like receptor antagonist SCH23390 increased the freezing response of the rats and
      selectively reduced Fos protein expression in the anterior cingulate cortex and
      rostral NAcSh. These findings confirm the involvement of the NAcSh in the
      expression of contextual fear memories and indicate the selective role of NAcSh
      D1-like receptors and anterior cingulate cortex in this process.

PMID- 22964038
TI  - Grading of a positive sputum smear and the risk of Mycobacterium tuberculosis
      transmission.
AB  - SETTING: After the diagnosis of a case of tuberculosis (TB), contact tracing is
      directed by the risk of transmission, for which sputum acid-fast bacilli (AFB)
      staining results are highly relevant. Limited data are available on the effect of
      the degree of acid-fast positivity, of a polymerase chain reaction (PCR) result
      or of bronchoalveolar lavage (BAL) fluid results on the risk of transmission.
      OBJECTIVES: To investigate factors associated with TB transmission, focusing on
      quantitative sputum smear results. DESIGN: Retrospective study of contact
      investigations performed over a period of 5 years in a Dutch Municipal Health
      Service among all index patients with TB, and the tuberculin skin test and chest
      radiography results in contacts. Three definitions of transmission were used: >=
      1 or >= 5 contacts with positive TST or active TB in contacts. RESULTS: The
      highest (+4/+5) sputum AFB grades were associated with the highest relative risk
      (>= 8) of extensive transmission or active TB among contacts. Novel risk factors
      observed were employment or school attendance, positive PCR of sputum and
      positive AFB staining of BAL fluid. Pulmonary symptoms, infiltrate or cavity and
      positive AFB sputum stain were also associated with transmission, confirming
      previous studies. CONCLUSION: The risk factors observed in this study may aid in
      the extension of contact investigations.

PMID- 22964039
TI  - Three approaches to time valuation in recreation demand: a study of the Snake
      River recreation area in eastern Washington.
AB  - Three travel cost models are used to estimate non-fishing recreation demand at
      the Snake River reservoirs recreation area in eastern Washington. The opportunity
      cost of time is specified in the "traditional" and McConnell-Strand models as a
      fraction of the exogenous market wage rate and in the two-step decision model as
      a function of socioeconomic attributes of the recreationists. Benefits per person
      per trip were $90, $35, and $46 respectively, for the three models. Boaters visit
      the site more than three times as often as non-boaters resulting in higher annual
      benefits for boaters.

PMID- 22964040
TI  - Mobilisation, alteration, and redistribution of monosulfidic sediments in inland
      river systems.
AB  - The accumulation of monosulfidic sediments in inland waterways is emerging as a
      major environmental issue. Mobilisation and suspension of monosulfidic sediments
      can result in deoxygenation, acidification of the water column and mobilisation
      of trace metals. The controls on monosulfidic sediment mobilisation and the
      critical thresholds for its scour and entrainment have not been established. This
      study examines the effect of a minor flood event (average return interval of 5
      years) on sulfidic sediment scour in the Wakool River in southern NSW, Australia.
      Five profiles were sampled within a small (~300 m) reach before and after a minor
      flood event to determine the degree of sediment scour and transport. The results
      indicate substantial scour of both monosulfidic sediments and underlying bed
      sediments (approximately 2100 m(3)). Changes in the sediment geochemistry suggest
      large concentrations of monosulfidic sediments had been suspended in the water
      column, partially-oxidised and redeposited. This is supported by (210)Pb results
      from one of the profiles. These results suggest that these monosulfidic sediments
      can move as bed load during minor flood events.

PMID- 22964041
TI  - A model for describing the eutrophication in a heavily regulated coastal lagoon.
      Application to the Albufera of Valencia (Spain).
AB  - A simplified two-dimensional eutrophication model was developed to simulate
      temporal and spatial variations of chlorophyll-a in heavily regulated coastal
      lagoons. This model considers the hydrodynamics of the whole study area, the
      regulated connexion of the lagoon with the sea, the variability of the input and
      output nutrient loads, the flux from the sediments to the water column, the
      phytoplankton growth and mortality kinetics, and the zooplankton grazing. The
      model was calibrated and validated by applying it to the Albufera of Valencia, a
      hypertrophic system whose connection to the sea is strongly regulated by a system
      of sluice-gates. The calibration and validation results presented a significant
      agreement between the model and the data obtained in several surveys. The
      accuracy was evaluated using a quantitative analysis, in which the average
      uncertainty of the model prediction was less than 6%. The results confirmed an
      expected phytoplankton bloom in April and October, achieving mean maximum values
      around 250 MUg l(-1) of chlorophyll-a. A mass balance revealed that the
      eutrophication process is magnified by the input loads of nutrients, mainly from
      the sediments, as well as by the limited connection of the lagoon with the sea.
      This study has shown that the developed model is an efficient tool to manage the
      eutrophication problem in heavily regulated coastal lagoons.

PMID- 22964042
TI  - Treatment of landfill leachate by using lateritic soil as a natural coagulant.
AB  - In this research, the capability of lateritic soil used as coagulant for the
      treatment of stabilized leachate from the Penang-Malaysia Landfill Site was
      investigated. The evaluation of lateritic soil coagulant in comparison with
      commercialized chemical coagulants, such as alum, was performed using
      conventional jar test experiments. The optimum pH and coagulant dosage were
      identified for the lateritic soil coagulant and the comparative alum coagulant.
      It was found that the application of lateritic soil coagulant was quite efficient
      in the removal of COD, color and ammoniacal-nitrogen content from the landfill
      leachate. The optimal pH value was 2.0, while 14 g/L of lateritic soil coagulant
      was sufficient in removing 65.7% COD, 81.8% color and 41.2% ammoniacal-nitrogen.
      Conversely, the optimal pH and coagulant dosage for the alum were pH 4.8 and 10
      g/L respectively, where 85.4% COD, 96.4% color and 47.6% ammoniacal-nitrogen were
      removed from the same leachate sample. Additionally, the Sludge Volume Index
      (SVI) ratio of alum and lateritic soil coagulant was 53:1, which indicated that
      less sludge was produced and was an environmentally friendly product. Therefore,
      lateritic soil coagulant can be considered a viable alternative in the treatment
      of landfill leachate.

PMID- 22964043
TI  - Can municipal wastewater treatment systems be carbon neutral?
AB  - Municipal wastewater treatment has emerged as one of the largest resource
      consumers in the US. As a result, the goal of municipal wastewater systems has
      extended from protecting receiving water and human health to improving the system
      sustainability. This study used the embodied energy and the associated carbon
      footprint to measure the resource consumption and recovery in wastewater systems.
      Three resource recovery methods were specifically investigated: onsite energy
      generation through combined heat and power systems, nutrient recycling through
      biosolids land application, and water reuse for residential irrigation. The
      embodied energy and the associated carbon footprint were estimated through an
      input-output based hybrid energy analysis method and carbon emission factors. A
      wastewater treatment plant in Tampa, Florida was studied to investigate the
      possibility of carbon neutrality of wastewater treatment systems. It was shown
      that the integrated resource (energy, nutrient and water) recovery has the
      potential to offset all the direct operational energy; however, it is not able to
      offset the total embodied energy of the treatment plant to achieve carbon
      neutrality. Among the three resource recovery methods, water reuse has the
      highest potential of offsetting carbon footprint, while nutrient recycling has
      the lowest.

PMID- 22964044
TI  - Sequence conservation in the Ancylostoma secreted protein-2 of Necator americanus
      (Na-ASP-2) from hookworm infected individuals in Thailand.
AB  - The Ancylostoma secreted protein-2 of Necator americanus (Na-ASP-2) was one of
      the promising vaccine candidates against the most prevalent human hookworm
      species as adverse vaccine reaction has compromised further human vaccine trials.
      To elucidate the gene structure and the extent of sequence diversity, we
      determined the complete nucleotide sequence of the Na-asp-2 gene of individual
      larvae from 32 infected subjects living in 3 different endemic areas of Thailand.
      Sequence analysis revealed that the gene encoding Na-ASP-2 comprised 8 exons. Of
      3 nucleotide substitutions in these exons, only one causes an amino acid change
      from leucine to methionine. A consensus conserved GT and AG at the 5' and the 3'
      boundaries of each intron was observed akin to those found in other eukaryotic
      genes. Introns of Na-asp-2 contained 23 nucleotide substitutions and 0-18 indels.
      The mean number of nucleotide substitutions per site (d) in introns was not
      significantly different from the mean number of synonymous substitutions per
      synonymous site (d(S)) in exons whereas d in introns was significantly exceeded
      d(N) (the mean number of nonsynonymous substitutions per nonsynonymous site) in
      exons (p<0.05), suggesting that introns and synonymous sites in exons may evolve
      at a similar rate whereas functional constraints at the amino acid could limit
      amino acid substitutions in Na-ASP-2. A recombination site was identified in an
      intron near the 3' portion of the gene. The positions of introns and the intron
      phases in the Na-asp-2 gene comparing with those in other pathogenesis-related-1
      proteins of Loa loa, Onchocerca volvulus, Heterodera glycines, Caenorhabditis
      elegans and human were relatively conserved, suggesting evolutionary conservation
      of these genes. Sequence conservation in Na-ASP-2 may not compromise further
      vaccine design if adverse vaccine effects could be resolved whereas
      microheterogeneity in introns of this locus may be useful for population genetics
      analysis of N. americanus.

PMID- 22964045
TI  - Rotavirus in diarrheal children in rural Burkina Faso: high prevalence of
      genotype G6P[6].
AB  - Group A rotavirus (RVA) is the most common cause of severe gastroenteritis in
      young children globally, and responsible for a significant number of deaths in
      African countries. While vaccines are available, trials have shown a lesser
      efficacy in Africa. One of the reasons could be the prevalence and/or emergence
      of unusual or novel RVA strains, as many strains detected in African countries
      remain uncharacterized. In this study, we characterized RVA positive specimens
      from two remote rural areas in Burkina Faso, West Africa. In total 56 RVA
      positive specimens were subgrouped by their VP6 gene, and G-and P typed by PCR
      and/or sequencing of the VP7 and VP4 genes, respectively. Notably, we found a
      high prevalence of the unusual G6P[6]SGI strains (23%). It was the second most
      common constellation after G9P[8]SGII (32%); and followed by G1P[8]SGII (20%) and
      G2P[4]SGI (9%). We also detected a G8P[6]SGI strain, for the first time in
      Burkina Faso. The intra-genetic diversity was high for the VP4 gene with two
      subclusters within the P[8] genotype and three subclusters within the P[6]
      genotype which were each associated with a specific G-type, thereby suggesting a
      genetic linkage. The G6P[6]SGI and other SGI RVA strains infected younger
      children as compared to SGII strains (p<0.05). To conclude, in this study we
      observed the emergence of unusual RVA strains and high genetic diversity of RVA
      in remote rural areas of Burkina Faso. The results highlight the complexity of
      RVA epidemiology which may have implication for the introduction of rotavirus
      vaccines currently being evaluated in many African countries.

PMID- 22964047
TI  - Kinetic performance comparison of a capillary monolithic and a fused-core column
      in micro-scale liquid chromatography.
AB  - The kinetic performance of monolithic and fused-core capillary C(18) columns was
      compared in isocratic-elution liquid chromatography. Heptanophenone was chosen as
      a test compound. The (u(0), H) couple obtained in a column with permeability
      K(v0) was transferred into a plate number, dead time (N, t(0)) couple and the
      kinetic plots were achieved by using a Kinetic Method Plot Analyzer template. The
      u(0,opt) (0.98 mm/s for the monolith and 1.05 mm/s for the fused-core column) and
      H(min) (17.58 MUm for the monolith and 18.08 MUm for the fused-core column)
      values determined from the van Deemter curve were found to be almost identical,
      whereas the N(opt) (the plate number for which the support achieves its best
      analysis time/pressure cost ratio) (150,000 for monolith and 41,000 for fused
      core column), maximal plate number, N(max) (the maximum plate number that can
      ever be reached with a support) (550,000 for monolith and 120,000 for the fused
      core column) and optimal analysis time, t(opt) (the time needed to obtain N(opt)
      plates) (18,583 s for the monolith and 4,068 s for the fused-core column)
      performance numbers determined from the kinetic plots were found to be
      significantly different.

PMID- 22964046
TI  - A new and improved strategy combining a dispersive-solid phase extraction-based
      multiclass method with ultra high pressure liquid chromatography for analysis of
      low molecular weight polyphenols in vegetables.
AB  - This paper reports on the development and optimization of a modified Quick, Easy,
      Cheap Effective, Rugged and Safe (QuEChERS) based extraction technique coupled
      with a clean-up dispersive-solid phase extraction (dSPE) as a new, reliable and
      powerful strategy to enhance the extraction efficiency of free low molecular
      weight polyphenols in selected species of dietary vegetables. The process
      involves two simple steps. First, the homogenized samples are extracted and
      partitioned using an organic solvent and salt solution. Then, the supernatant is
      further extracted and cleaned using a dSPE technique. Final clear extracts of
      vegetables were concentrated under vacuum to near dryness and taken up into
      initial mobile phase (0.1% formic acid and 20% methanol). The separation and
      quantification of free low molecular weight polyphenols from the vegetable
      extracts was achieved by ultrahigh pressure liquid chromatography (UHPLC)
      equipped with a phodiode array (PDA) detection system and a Trifunctional High
      Strength Silica capillary analytical column (HSS T3), specially designed for
      polar compounds. The performance of the method was assessed by studying the
      selectivity, linear dynamic range, the limit of detection (LOD) and limit of
      quantification (LOQ), precision, trueness, and matrix effects. The validation
      parameters of the method showed satisfactory figures of merit. Good linearity
      (Rvalues2>0.954; (+)-catechin in carrot samples) was achieved at the studied
      concentration range. Reproducibility was better than 3%. Consistent recoveries of
      polyphenols ranging from 78.4 to 99.9% were observed when all target vegetable
      samples were spiked at two concentration levels, with relative standard
      deviations (RSDs, n=5) lower than 2.9%. The LODs and the LOQs ranged from 0.005
      MUg mL(-1) (trans-resveratrol, carrot) to 0.62 MUg mL(-1) (syringic acid, garlic)
      and from 0.016 MUg mL(-1) (trans-resveratrol, carrot) to 0.87 MUg mL(-1) ((+)
      catechin, carrot) depending on the compound. The method was applied for studying
      the occurrence of free low molecular weight polyphenols in eight selected dietary
      vegetables (broccoli, tomato, carrot, garlic, onion, red pepper, green pepper and
      beetroot), providing a valuable and promising tool for food quality evaluation.

PMID- 22964048
TI  - Improved chemical stabilities for end-capped high performance liquid
      chromatography stationary phases based on poly(methyloctadecylsiloxane) thermally
      immobilized onto metalized silicas.
AB  - Endcapped stationary phases were prepared after thermal immobilization of
      poly(methyloctadecylsiloxane) (PMODS) onto zirconized and titanized silica
      supports. These new stationary phases have lower densities of residual hydroxyl
      groups, according to infrared spectroscopy and 29Si CP-MAS NMR and as shown by
      the symmetrical peaks of basic compounds from the Tanaka, Engelhardt and SRM 870
      test mixtures. Stability tests for the endcapped stationary phases, measured
      using severe alkaline conditions (70:30 (v/v) methanol:0.05 mol/L K2CO3/KHCO3, pH
      10, 50  degrees C), revealed that the stabilities of these phases are greater
      than the stabilities of similar nonendcapped phases. The stationary phases showed
      good performance for the separation of basic pharmaceuticals.

PMID- 22964049
TI  - Impact of the BEA zeolite morphology on isobutane adsorption followed by Reversed
      Flow Inverse Gas Chromatography.
AB  - The mass transfer phenomena of isobutane (i-C4) were investigated at 343K on
      three protonic BEA zeolites. Defined by their crystallites sizes and degrees of
      aggregation, these samples were characterized by Reversed-Flow Inverse Gas
      Chromatography (RF-GC). This simple technique, used in conjunction with numerical
      computation, allowed the determination of physicochemical quantities like local
      monolayer capacities, probability density functions and diffusion coefficients in
      a time-resolved way. This study enabled to conclude that the effective diffusion
      coefficient was affected by the size of the zeolite agglomerate whereas the
      surface diffusion depended on the zeolite crystallite size.

PMID- 22964050
TI  - Comparative enantioseparation of talinolol in aqueous and non-aqueous capillary
      electrophoresis and study of related selector-selectand interactions by nuclear
      magnetic resonance spectroscopy.
AB  - The enantiomers of the chiral beta-blocker drug talinolol were separated with two
      single component sulfated beta-cyclodextrin (CD) derivatives, namely heptakis
      (2,3-di-O-methyl-6-sulfo)-beta-CD) (HDMS-beta-CD) and heptakis (2,3-di-O-acetyl-6
      sulfo)-beta-CD) (HDAS-beta-CD), in aqueous and non-aqueous capillary
      electrophoresis (CE). The enantiomer affinity pattern of talinolol toward these
      two CDs was opposite in both aqueous and non-aqueous CE. However, the enantiomer
      affinity pattern for a given CD derivative did not change when aqueous buffer was
      replaced with non-aqueous background electrolyte. The structures of the analyte
      selector complexes in both, aqueous and non-aqueous electrolytes were studied
      using rotating frame nuclear Overhauser effect (ROESY) NMR spectroscopy.
      Inclusion complex formation between the enantiomers of talinolol and HDAS-beta-CD
      was confirmed in aqueous buffer, while the complex between the enantiomers of
      talinolol and HDMS-beta-CD was of the external type. The complex of the talinolol
      enantiomers with HDAS-beta-CD in non-aqueous electrolyte was also of the external
      type. In spite of external complex formation excellent separation of the
      enantiomers was observed in non-aqueous CE.

PMID- 22964051
TI  - What is the future of (ultra) high performance liquid chromatography coupled to
      low and high resolution mass spectrometry for toxicological drug screening?
AB  - This paper reviews critically LC-MS approaches for toxicological drug screening
      using (ultra) high performance liquid chromatography (UHPLC) coupled to low and
      high resolution mass spectrometry (HRMS) published since 2010. A concluding
      discussion focuses on progress and current status of sample workup, separation by
      HPLC vs. UHPLC, MS detection modes and their specificity, universality of LC-MS
      libraries, and validation necessary of LC-MS for screening methods. Finally, a
      discussion on what the future holds for LC-MS drug screening in clinical and
      forensic toxicology completes this review article.

PMID- 22964052
TI  - A method of calculating the second dimension hold-up time for comprehensive two
      dimensional gas chromatography.
AB  - A method of calculating the second dimension hold-up time for comprehensive two
      dimensional gas chromatographic (GC*GC) data was developed by incorporating the
      temperature information of the second dimension column into the calculation
      model. The model was developed by investigating the relationship between the
      coefficients in each of six literature reported nonlinear models and the
      relationship between each coefficient and the second dimension column
      temperature. The most robust nonlinear function was selected and further used to
      construct the new model for calculation of the second dimension retention time,
      in which the coefficients that have significant correlation with the column
      temperature are replaced with expressions of column temperature. An advantage of
      the proposed equation is that eight parameters could explain the second dimension
      hold-up time as well as retention time corresponding to n-alkanes and column
      temperature in the entire chromatographic region, including the chromatographic
      region not bounded by the retention times of n-alkanes. To optimize the
      experimental design for collecting the isothermal data of n-alkanes to create the
      second dimension hold-up time model, the column temperature difference and the
      number of isothermal experiments should be considered simultaneously. It was
      concluded that a total of 5 or 6 isothermal experiments with temperature
      difference of 40 or 50  degrees C are enough to generate an accurate model. The
      test mean squared error (MSE) of those conditions ranges from 0.0428 to 0.0532
      for calculation of the second dimension hold-up time for GC*GC data.

PMID- 22964053
TI  - Increasing set size breaks down sequential congruency: evidence for an
      associative locus of cognitive control.
AB  - In recent years, a number of studies have revealed that cognitive control is
      strongly context-dependent (e.g., Crump et al., 2006). Inspired by this,
      computational models have been formulated based on the idea that cognitive
      control processes are based on associative learning (Blais et al., 2007; Verguts
      & Notebaert, 2008). Here, we test a natural consequence of this idea, namely,
      that sequential congruency effects (Gratton et al., 1992) should gradually
      decrease with an increasing number of task-relevant features (e.g., stimuli). The
      effect is empirically observed and simulated in a computational model.
      Implications of our findings are discussed.

PMID- 22964054
TI  - The effects of voluntary movements on auditory-haptic and haptic-haptic temporal
      order judgments.
AB  - In two experiments we investigated the effects of voluntary movements on temporal
      haptic perception. Measures of sensitivity (JND) and temporal alignment (PSS)
      were obtained from temporal order judgments made on intermodal auditory-haptic
      (Experiment 1) or intramodal haptic (Experiment 2) stimulus pairs under three
      movement conditions. In the baseline, static condition, the arm of the
      participants remained stationary. In the passive condition, the arm was displaced
      by a servo-controlled motorized device. In the active condition, the participants
      moved voluntarily. The auditory stimulus was a short, 500Hz tone presented over
      headphones and the haptic stimulus was a brief suprathreshold force pulse applied
      to the tip of the index finger orthogonally to the finger movement. Active
      movement did not significantly affect discrimination sensitivity on the auditory
      haptic stimulus pairs, whereas it significantly improved sensitivity in the case
      of the haptic stimulus pair, demonstrating a key role for motor command
      information in temporal sensitivity in the haptic system. Points of subjective
      simultaneity were by-and-large coincident with physical simultaneity, with one
      striking exception in the passive condition with the auditory-haptic stimulus
      pair. In the latter case, the haptic stimulus had to be presented 45ms before the
      auditory stimulus in order to obtain subjective simultaneity. A model is proposed
      to explain the discrimination performance.

PMID- 22964055
TI  - Serial position effects in the identification of letters, digits, symbols, and
      shapes in peripheral vision.
AB  - Three experiments measured serial position functions for character-in-string
      identification in peripheral vision. In Experiment 1, random strings of five
      letters (e.g., P F H T M) or five symbols (e.g., lambda B P Psi Y) were briefly
      presented to the left or to the right of fixation, and identification accuracy
      was measured at each position in the string using a post-cued two-alternative
      forced-choice task (e.g., was there a T or a B at the 4th position). In
      Experiment 2 the performance to letter stimuli was compared with familiar two
      dimensional shapes (e.g., square, triangle, circle), and in Experiment 3 we
      compared digit strings (e.g., 6 3 7 9 2) with a set of keyboard symbols (e.g., %
      S @ < ?). Eye-movements were monitored to ensure central fixation. The results
      revealed a triple interaction between the nature of the stimulus (letters/digits
      vs. symbols/shapes), eccentricity, and visual field. In all experiments this
      interaction reflected a selective left visual field advantage for letter or digit
      stimuli compared with symbol or shape stimuli for targets presented at the
      greatest eccentricity. The results are in line with the predictions of the
      modified receptive field hypothesis proposed by Tydgat and Grainger (2009), and
      the predictions of the SERIOL2 model of letter string encoding.

PMID- 22964056
TI  - Haptic perception of wetness.
AB  - In daily life, people interact with textiles of different degrees of wetness, but
      little is known about the mechanics of wetness perception. This paper describes
      an experiment with six conditions regarding haptic discrimination of the wetness
      of fabrics. Three materials were used: cotton wool, sponge-structured viscose and
      thin viscose. Two ways of touching were investigated: static touching, in which
      only thermal cues were available, and dynamic touching, in which additional
      mechanical cues were available. For dynamic touching, average Weber fractions for
      discrimination were around 0.3, whereas for static touching, they ranged from
      0.34 to 0.63. The results show that people can make use of the additional
      mechanical cues to significantly improve their discrimination performance. There
      was no significant difference between Weber fractions for the three materials,
      showing that wetness can be judged as a separate perceptual quantity, independent
      of the material.

PMID- 22964057
TI  - Implicit body representations and the conscious body image.
AB  - Recent studies have revealed that somatosensory processing relies on a class of
      implicit body representations showing large distortions of size and shape. The
      relation between these representations and the conscious body image remains
      unclear. Dissociations have been reported in the clinical literature on eating
      disorders between different body image measures, with larger and more consistent
      distortions found with depictive measures, in which participants compare their
      body to a visual depiction of a body, than metric measures, in which participants
      compare their body to some non-body standard. Here, we compared implicit body
      representations underlying position sense to the body image measured with both
      depictive and metric methods. The body image was measured using both a depictive
      method (template matching) in which participants judged whether their hand was
      wider or more slender than a shown hand picture, and a metric method (line
      length) in which participants judged whether different parts of their hand were
      shorter or longer than a presented line. Consistent with previous findings,
      characteristic distortions were found for the implicit body representation
      underlying position sense. These distortions were also found in attenuated form
      for metric - but not depictive - body image measures. While replicating the basic
      dissociation between implicit body representations and the conscious body image,
      these results demonstrate that this dissociation is not absolute and specific
      tasks may utilise both to varying degrees depending on task demands. Metric
      measures may not be pure measures of body image, but some combination of visual
      and somatosensory body representations.

PMID- 22964058
TI  - Individual differences in the rubber-hand illusion: predicting self-reports of
      people's personal experiences.
AB  - Can we assess individual differences in the extent to which a person perceives
      the rubber-hand illusion on the basis of self-reported experiences? In this
      research, we develop such an instrument using Rasch-type models. In our
      conception, incorporating an object (e.g., a rubber hand) into one's body image
      requires various sensorimotor and cognitive processes. The extent to which people
      can meet these requirements thus determines how intensely people experience and,
      simultaneously, describe the illusion. As a consequence, individual differences
      in people's susceptibility to the rubber-hand illusion can be determined by
      inspecting reports of their personal experiences. The proposed model turned out
      to be functional in its capability to predict self-reports of people's
      experiences and to reliably assess individual differences in susceptibility to
      the illusion. Regarding validity, we found a small, but significant, correlation
      between individual susceptibility and proprioceptive drift. Additionally, we
      found that asynchrony, and tapping rather than stroking the fingers constrain the
      experience of the illusion.

PMID- 22964059
TI  - The effect of question expectedness and experience on lying about intentions.
AB  - In recent years researchers have started to focus on lying about intentions
      (Granhag, 2010). In the present experiment participants were interviewed about
      their forthcoming trip. We tested the hypothesis that liars (N=43) compared to
      truth tellers (N=43) would give fewer details to unexpected questions about
      planning, transportation and the core event, but an equal amount or more detail
      to expected questions about the purpose of the trip. We also tested the
      hypothesis that participants who had previously experienced the intention (i.e.,
      they had made such a trip before) would give more detail than those who had never
      experienced the intended action. The unexpected question hypothesis was
      supported, whereas the previous experience effect only emerged in interactions.
      The benefit of using different types of questions for lie detection purposes is
      discussed.

PMID- 22964060
TI  - A campaign for information and diagnosis of atrial fibrillation: "pulse week".
AB  - INTRODUCTION AND OBJECTIVES: Atrial fibrillation occurs in 5%-15% of elderly
      patients and causes one-fourth to one-fifth of all cerebrovascular events. These
      patients are frequently asymptomatic. We conducted a public campaign aiming to
      evaluate the effectiveness of a program for information on and diagnosis of
      atrial fibrillation in individuals aged 65 years old or more from the primary
      care perspective. METHODS: We sent letters containing informative materials and
      an invitation to attend a special nurse appointment to all individuals>=65 years
      old, without a previous diagnosis of atrial fibrillation or flutter. Patients
      were from 3 specific areas in Pontevedra province. The procedures were performed
      according to a specially designed program called "Pulse Week" within 5 working
      days. A group of trained nurses obtained a brief medical history and performed
      pulse palpation for 15 s and blood pressure measurement. A complete 12-lead
      electrocardiogram was performed if arrhythmic pulsations were detected. RESULTS:
      A total of 8869 letters were sent. During the specified week, 1532 individuals
      were evaluated (877 women); the mean age was 72.5 (6.5) years old, 833 had
      hypertension (54%), 232 had diabetes (15%), 61 had previous stroke (4%) and 88
      had had a myocardial infarction (6%). Electrocardiograms were performed in 187
      patients. There were 17 patients with newly diagnosed atrial fibrillation.
      CONCLUSIONS: A public, 5-day campaign based on pulse palpation and targeting
      elderly individuals had little impact on the detection of new cases of atrial
      fibrillation in our environment.

PMID- 22964061
TI  - Serum adiponectin level as a biomarker of coronary artery calcification and
      severe coronary lesions.

PMID- 22964062
TI  - A sensitivity analysis of a personalized pulse wave propagation model for
      arteriovenous fistula surgery. Part A: Identification of most influential model
      parameters.
AB  - Previously, a pulse wave propagation model was developed that has potential in
      supporting decision-making in arteriovenous fistula (AVF) surgery for
      hemodialysis. To adapt the wave propagation model to personalized conditions,
      patient-specific input parameters should be available. In clinics, the number of
      measurable input parameters is limited which results in sparse datasets. In
      addition, patient data are compromised with uncertainty. These uncertain and
      incomplete input datasets will result in model output uncertainties. By means of
      a sensitivity analysis the propagation of input uncertainties into output
      uncertainty can be studied which can give directions for input measurement
      improvement. In this study, a computational framework has been developed to
      perform such a sensitivity analysis with a variance-based method and Monte Carlo
      simulations. The framework was used to determine the influential parameters of
      our pulse wave propagation model applied to AVF surgery, with respect to
      parameter prioritization and parameter fixing. With this we were able to
      determine the model parameters that have the largest influence on the predicted
      mean brachial flow and systolic radial artery pressure after AVF surgery. Of all
      73 parameters 51 could be fixed within their measurement uncertainty interval
      without significantly influencing the output, while 16 parameters importantly
      influence the output uncertainty. Measurement accuracy improvement should thus
      focus on these 16 influential parameters. The most rewarding are measurement
      improvements of the following parameters: the mean aortic flow, the aortic
      windkessel resistance, the parameters associated with the smallest arterial or
      venous diameters of the AVF in- and outflow tract and the radial artery
      windkessel compliance.

PMID- 22964063
TI  - A novel non-linear recursive filter design for extracting high rate pulse
      features in nuclear medicine imaging and spectroscopy.
AB  - Applications in imaging and spectroscopy rely on pulse processing methods for
      appropriate data generation. Often, the particular method utilized does not
      highly impact data quality, whereas in some scenarios, such as in the presence of
      high count rates or high frequency pulses, this issue merits extra consideration.
      In the present study, a new approach for pulse processing in nuclear medicine
      imaging and spectroscopy is introduced and evaluated. The new non-linear
      recursive filter (NLRF) performs nonlinear processing of the input signal and
      extracts the main pulse characteristics, having the powerful ability to recover
      pulses that would ordinarily result in pulse pile-up. The filter design defines
      sampling frequencies lower than the Nyquist frequency. In the literature, for
      systems involving NaI(Tl) detectors and photomultiplier tubes (PMTs), with a
      signal bandwidth considered as 15 MHz, the sampling frequency should be at least
      30 MHz (the Nyquist rate), whereas in the present work, a sampling rate of 3.3
      MHz was shown to yield very promising results. This was obtained by exploiting
      the known shape feature instead of utilizing a general sampling algorithm. The
      simulation and experimental results show that the proposed filter enhances count
      rates in spectroscopy. With this filter, the system behaves almost identically as
      a general pulse detection system with a dead time considerably reduced to the new
      sampling time (300 ns). Furthermore, because of its unique feature for
      determining exact event times, the method could prove very useful in time-of
      flight PET imaging.

PMID- 22964064
TI  - A sensitivity analysis of a personalized pulse wave propagation model for
      arteriovenous fistula surgery. Part B: Identification of possible generic model
      parameters.
AB  - Decision-making in vascular access surgery for hemodialysis can be supported by a
      pulse wave propagation model that is able to simulate pressure and flow changes
      induced by the creation of a vascular access. To personalize such a model,
      patient-specific input parameters should be chosen. However, the number of input
      parameters that can be measured in clinical routine is limited. Besides, patient
      data are compromised with uncertainty. Incomplete and uncertain input data will
      result in uncertainties in model predictions. In part A, we analyzed how the
      measurement uncertainty in the input propagates to the model output by means of a
      sensitivity analysis. Of all 73 input parameters, 16 parameters were identified
      to be worthwhile to measure more accurately and 51 could be fixed within their
      measurement uncertainty range, but these latter parameters still needed to be
      measured. Here, we present a methodology for assessing the model input parameters
      that can be taken constant and therefore do not need to be measured. In addition,
      a method to determine the value of this parameter is presented. For the pulse
      wave propagation model applied to vascular access surgery, six patient-specific
      datasets were analyzed and it was found that 47 out of 73 parameters can be fixed
      on a generic value. These model parameters are not important for personalization
      of the wave propagation model. Furthermore, we were able to determine a generic
      value for 37 of the 47 fixable model parameters.

PMID- 22964065
TI  - Roux-en-Y gastric bypass-associated bowel obstruction complicating pregnancy-an
      obstetrician's map to the clinical minefield.
AB  - Over 80% of patients undergoing bariatric surgery are women, approximately half
      of whom are of reproductive age. The most common procedure in the United States
      is the Roux-en-Y gastric bypass. Small bowel obstruction is one of many
      recognized postoperative complications. For such a serious condition, this entity
      presents with remarkable subtlety and is easily misdiagnosed, particularly in
      pregnant women. The consequences of late recognition can be life-threatening to
      both mother and fetus. We aim to decrease preventable maternal and perinatal
      morbidity and mortality by revealing diagnostic and therapeutic missteps related
      to Roux-en-Y gastric bypass-associated small bowel obstruction.

PMID- 22964066
TI  - Early prenatal diagnosis of tricuspid stenosis.
AB  - Although the prenatal diagnosis of heart anomalies has improved dramatically
      during the last 2 decades, the diagnosis of heart anomalies remains a challenge.
      Tricuspid stenosis has not been previously diagnosed in the early second
      trimester. The sonographic signs of early detection of tricuspid stenosis at 15
      weeks of gestation included normal sized right atrium, small right ventricle,
      narrow pulmonary artery, and diminished flow through the tricuspid valve. The
      diagnosis was confirmed by postabortal examination. In this case report we
      describe, for the first time, early prenatal diagnosis of tricuspid stenosis at
      15 weeks' gestational age.

PMID- 22964067
TI  - Outcomes in women age 40 years and older with cytologically benign endometrial
      cells.
AB  - OBJECTIVE: We sought to estimate cytologically benign endometrial cell (CBEC)
      associated endometrial hyperplasia and cancer rates, and describe clinical and
      histologic outcomes. STUDY DESIGN: Medical records of women age >40 years with
      CBEC in 2005 through 2010 were reviewed for clinical characteristics; assessment
      with endometrial biopsy, ultrasound, or hysteroscopy; and consequent outcomes.
      RESULTS: Of 658 women, 281 (42.7%) were assessed: 39.4% of 330 premenopausal, and
      46.0% of 328 postmenopausal women. Among these, cancer rate was 3.6% and differed
      between premenopausal (0.8%) and postmenopausal (6.0%) women (P = .019).
      Hyperplasia rate was similar in premenopausal (3.9%) and postmenopausal (3.3%)
      women. Of 20 assessed women with endometrial pathology, 4 (1 premenopausal) women
      with cancer and 4 (2 premenopausal) women with hyperplasia had no abnormal
      bleeding. CONCLUSION: Cancer was more common in postmenopausal women with
      assessed CBEC while hyperplasia was comparably distributed between premenopausal
      and postmenopausal women. Findings support CBEC assessment regardless of
      menopausal status or abnormal bleeding.

PMID- 22964068
TI  - A population-based study of the risk of repeat clinical chorioamnionitis in
      Washington State, 1989-2008.
AB  - OBJECTIVE: Chorioamnionitis can cause severe complications for the infant;
      therefore, characterization of the risk of recurrence and identification of the
      factors that modify it are clinically relevant to pregnant women and their
      providers. STUDY DESIGN: The risk of recurrence was examined in a retrospective
      population-based cohort study with the use of birth certificate and delivery
      hospitalization discharge data from Washington State for the years 1989-2008.
      RESULTS: Women who had chorioamnionitis in their first deliveries were 3.43 times
      as likely to have chorioamnionitis in their second deliveries as were women who
      did not have chorioamnionitis in their first deliveries (95% confidence interval
      [CI], 2.67-4.42; P < .001). Smoking status modified this association (smokers:
      odds ratio, 1.38 [95% CI, 0.62-3.08]; nonsmokers: odds ratio, 3.80 [95% CI, 2.88
      5.00]). CONCLUSION: These data provide strong evidence for the occurrence of
      repeat chorioamnionitis; the association is strongest in women who do not smoke
      during pregnancy.

PMID- 22964069
TI  - Researchers should convince policy makers to perform a classic cluster randomized
      controlled trial instead of a stepped wedge design when an intervention is rolled
      out.

PMID- 22964070
TI  - Use of the stepped wedge design cannot be recommended: a critical appraisal and
      comparison with the classic cluster randomized controlled trial design.

PMID- 22964072
TI  - Asthma and the menopause: a systematic review and meta-analysis.
AB  - OBJECTIVE: To review the available literature to determine whether the menopausal
      transition is associated with asthma incidence. METHODS: We performed a
      systematic review and meta-analysis of cohort and cross-sectional studies
      providing a definition/assessment of menopausal status, incidence or prevalence
      of a defined diagnosis of asthma, and providing a measure of the association or
      of menopausal state and asthma or enough data for a calculation of this
      association. Where possible these meta-analytic estimates were also stratified by
      intake of menopausal hormone therapy (MHT). RESULTS: Of 76 potentially relevant
      articles, 8 studies met the inclusion criteria and were included in the review,
      and 6 in the meta-analysis. There was heterogeneity across studies: four studies
      reported slightly increased prevalence rates of asthma in post-menopause, one
      large cohort yielded a lower asthma incidence and one cross-sectional study a
      lower prevalence in post-menopause. Overall, the meta-analysis showed no
      significant association between menopause and asthma rates. When stratifying by
      use of MHT, the association between menopause and asthma rates was increased in
      women reporting use of MHT (RR 1.32, 95%CI 1.01-1.74), but not in women not using
      MHT. CONCLUSION: We found no significant association of menopause with asthma
      prevalence or incidence except for women reporting use of MHT. However, these
      findings result from a small number of studies, including only 1 large cohort
      with incidence rates for pre- as well as post-menopause. Further studies are
      needed addressing more closely subgroup analyses and a possible modification of
      the association of menopause and asthma by MHT.

PMID- 22964071
TI  - Systematic review of predictive performance of injury severity scoring tools.
AB  - Many injury severity scoring tools have been developed over the past few decades.
      These tools include the Injury Severity Score (ISS), New ISS (NISS), Trauma and
      Injury Severity Score (TRISS) and International Classification of Diseases (ICD)
      based Injury Severity Score (ICISS). Although many studies have endeavored to
      determine the ability of these tools to predict the mortality of injured
      patients, their results have been inconsistent. We conducted a systematic review
      to summarize the predictive performances of these tools and explore the
      heterogeneity among studies. We defined a relevant article as any research
      article that reported the area under the Receiver Operating Characteristic curve
      as a measure of predictive performance. We conducted an online search using
      MEDLINE and Embase. We evaluated the quality of each relevant article using a
      quality assessment questionnaire consisting of 10 questions. The total number of
      positive answers was reported as the quality score of the study. Meta-analysis
      was not performed due to the heterogeneity among studies. We identified 64
      relevant articles with 157 AUROCs of the tools. The median number of positive
      answers to the questionnaire was 5, ranging from 2 to 8. Less than half of the
      relevant studies reported the version of the Abbreviated Injury Scale (AIS)
      and/or ICD (37.5%). The heterogeneity among the studies could be observed in a
      broad distribution of crude mortality rates of study data, ranging from 1% to
      38%. The NISS was mostly reported to perform better than the ISS when predicting
      the mortality of blunt trauma patients. The relative performance of the ICSS
      against the AIS-based tools was inconclusive because of the scarcity of studies.
      The performance of the ICISS appeared to be unstable because the performance
      could be altered by the type of formula and survival risk ratios used. In
      conclusion, high-quality studies were limited. The NISS might perform better in
      the mortality prediction of blunt injuries than the ISS. Additional studies are
      required to standardize the derivation of the ICISS and determine the relative
      performance of the ICISS against the AIS-based tools.

PMID- 22964073
TI  - Determinants of the decision to perform prophylactic oophorectomy in association
      with a hysterectomy for a benign condition.
AB  - BACKGROUND: The decision to perform an elective bilateral salpingo-oophorectomy
      (BSO) at the time of a hysterectomy for a benign condition is complex. AIM: To
      assess the determinants of the decision to proceed to a prophylactic BSO during a
      hysterectomy for a benign condition. MATERIALS AND METHODS: We collected
      demographic and clinical data, including age, menopausal status and risk of
      ovarian cancer. Using a regression model we analysed the decision perform a
      prophylactic BSO in women successively admitted for a hysterectomy for a benign
      condition, in relation to the collected demographic and clinical data. RESULTS:
      Data were collected for 43 women, aged between 37 and 65 years (mean age 48.6
      years, SD 6.9), on the day before their hysterectomy. Thirty-six (84%) had a
      total hysterectomy and 7 (16%) a subtotal hysterectomy; 40 (93%) had a
      laparoscopic procedure. Prophylactic BSO was significantly associated with age:
      none of the women aged under 40 years had the procedure, compared with 8% of
      those aged 41-45 years, 29% of those aged 46-50 years and 83% of those aged 51
      years or more (chi(2)=23; P<0.001). Of the postmenopausal women, 67% had a
      prophylactic BSO, compared with 24% of the premenopausal women (chi(2)=6;
      P<0.047). In this small series of patients no relationship was found between the
      decision to perform a BSO and the risk of ovarian cancer. Age was the only
      significant variable in the regression model (pseudo R(2) Nagelkerke=0.6,
      P<0.05). CONCLUSION: The physician's recommendation to perform an elective BSO at
      the time of a hysterectomy for a benign condition is strongly influenced by the
      patients' age.

PMID- 22964074
TI  - Risk factors associated with tuberculosis infection among health care workers in
      Inner Mongolia, China.
AB  - SETTING: Health care workers (HCWs) are at increased risk for tuberculosis (TB)
      infection. In China, surveys examining TB infection among HCWs have not studied
      general health care facilities, compared tuberculin tests conducted using local
      protocols against an internationally accepted  test or characterised risk
      factors. OBJECTIVE: To measure the prevalence of and risk factors for TB
      infection among HCWs in Inner Mongolia, China. DESIGN: Between April and August
      2010, we administered QuantiFERON(r)-TB Gold In-Tube (QFT-GIT) tests, skin tests
      using Chinese tuberculin  (TST) and surveys among HCWs at an infectious diseases
      hospital and a general medical hospital. We assessed whether demographic
      characteristics, personal exposure and work exposure were associated with QFT-GIT
      and TST positivity, and assessed agreement between test results. RESULTS: Of  999
      HCWs, 683 (68%) were QFT-GIT-positive, which was associated with greater age,
      longer HCW career, TB disease in a co-worker and greater daily patient exposure
      using multivariable analysis. TST reactions >= 5 mm occurred in 69% of the HCWs;
      agreement between test results was low ( 0.22). CONCLUSIONS: The prevalence of TB
      infection among HCWs in Inner Mongolia is high; infection was associated with
      occupational exposure. Results from locally conducted TST are difficult to
      interpret. In China, TB infection control in health care facilities should be
      strengthened.

PMID- 22964076
TI  - Prediction and limitation of polymer degradation in Environmental SEM.
AB  - Polymer materials degradation is a well-known limitation to their
      characterization in SEM. In this paper authors present an additional possibility
      for polymer imaging offered by the Environmental SEM applied to the PMMA with
      micrometric relief. As shown by the so-called double-scan procedure, increasing
      the pressure enables to delay the degradation of the polymer surface. To evaluate
      quantitatively this observation, the classical formula to calculate the electron
      dose is adapted to ESEM characteristic. It is shown first that pressure enables
      to decrease the electron dose and all that takes place as if the skirt electrons
      do not participate in the irradiation. Secondly this procedure allows to obtain
      the critical dose of topographic degradation, applied to the PMMA with
      micrometric relief D(C) was found to be 1.31 +/- 0.28 Cm(-2). Finally it becomes
      then possible, knowing the D(C) for a given sample, to evaluate the limit of
      investigation without topographic surface degradation: for example, the maximal
      field of view (linked to the magnification) depending on the other parameters.

PMID- 22964075
TI  - Cyclin-dependent kinase-5 and p35/p25 activators in schizophrenia and major
      depression prefrontal cortex: basal contents and effects of psychotropic
      medications.
AB  - Cyclin-dependent kinase-5 (CDK5) and p35/p25 activators, interacting with the
      exocytotic machinery (e.g. munc18-1 and syntaxin-1A), play critical roles in
      neurosecretion. The basal status of CDK5/p35/p25 and the effect of psychotropic
      drugs (detected in blood/urine samples) were investigated in post-mortem
      prefrontal cortex (PFC)/Brodmann's area 9 of schizophrenia (SZ) and major
      depression (MD) subjects. In SZ (all subjects, n = 24), CDK5 and p35, but not
      p25, were reduced (-28 to -58%) compared to controls. In SZ antipsychotic-free (n
      = 12), activator p35 was decreased (-52%). In SZ antipsychotic-treated (n = 12),
      marked reductions of CDK5 (-47%), p35 (-76%) and p25 (-36%) were quantified. In
      MD (n = 13), including antidepressant-free/treated subgroups, CDK5, p35 and p25
      were unaltered. In SZ (n = 24), CDK5, p35 or p25 correlated with munc18-1a, but
      not with syntaxin-1A. The results demonstrate reduced p35 basal content and down
      regulation of CDK5/p35/p25 by antipsychotics in SZ. The suggested CDK5/munc18-1a
      functional interaction may lead to dysregulated neurosecretion in SZ PFC.

PMID- 22964077
TI  - Primary non-adherence to prescribed medication in general practice: lack of
      influence of moderate increases in patient copayment.
AB  - BACKGROUND: Primary non-adherence refers to the patient not redeeming a
      prescribed medication at some point during drug therapy. Research has mainly
      focused on secondary non-adherence. Prior to this study, the overall rate of
      primary non-adherence in general practice in Iceland was not known. OBJECTIVES:
      To determine the prevalence of primary non-adherence, test whether it is
      influenced by a moderate increase in patient copayment implemented in 2010 and
      examine the difference between copayment groups (general versus concession
      patients). METHODS: A population-based data linkage study, wherein prescriptions
      issued electronically by 140 physicians at 16 primary health care centres in the
      Reykjavik capital area during two periods before and after increases in copayment
      were matched with those dispensed in pharmacies, the difference constituting
      primary non-adherence (population: 200&emsp14;000; patients: 21&emsp14;571;
      prescriptions: 22&emsp14;991). Eight drug classes were selected to reflect
      symptom relief and degree of copayment. Two-tailed chi-square test and odds
      ratios for non-adherence by patient copayment groups were calculated. RESULTS:
      The rate of primary non-adherence was 6.2%. It was lower after the increased
      copayment, reaching statistical significance for hypertensive agents, non
      steroidal anti-inflammatory drugs (NSAIDs) and antipsychotics. Generally, primary
      non-adherence, except for antibacterials and NSAIDs, was highest in old-age
      pensioners. CONCLUSIONS: Primary non-adherence in Icelandic general practice was
      within the range of prior studies undertaken in other countries and was not
      adversely affected by the moderate increase in patient copayment. Older patients
      showed a different pattern of primary non-adherence. This may possibly be
      explained by higher prevalence of medicine use.

PMID- 22964078
TI  - Bereavement care in general practice: a cluster-randomized clinical trial.
AB  - BACKGROUND: The loss of a loved person may lead to complicated grief (CG).
      General practitioners (GPs) consider bereavement care to be important but find
      training for this task to be insufficient. We hypothesized that improvement in
      skills that facilitate early identification of CG and enhance GPs' clinical care
      may reduce adverse health outcomes. Aim. To test whether implementation of a
      bereavement management program in general practice could improve the GPs' ability
      to identify CG and provide clinical care. DESIGN: A cluster-randomized controlled
      trial allocating GPs and their listed patients suffering from bereavement to
      either a intervention or a control group. SETTING: Close relatives of patients
      who had died from cancer in Denmark were recruited (N = 402). METHOD: The primary
      outcomes were defined as the bereaved relatives' score on the Beck's Depression
      Inventory II and the Inventory of Complicated Grief-Revised (ICG-R), the GP's
      clinical assessment of the relative's grief reaction and the relative's number of
      contacts with general practice. RESULTS: Larger improvements in ICG-R scores were
      found in the intervention group than in the control group. In the intervention
      group, patients exhibiting CG symptoms were more likely to receive supportive
      care and to be referred to mental health practitioners, whereas GP's in the
      control group more often prescribed psychotropic drugs for patients with symptoms
      of CG. The GP's ability to identify CG at 13 months did not seem to be better in
      the intervention group than in the control group. CONCLUSION: While only
      statistically near significant, we found some indications of an effect of the
      intervention compared with usual care. Our results underscore the need for
      improving GPs' clinical skills in identifying patients with CG.

PMID- 22964080
TI  - Screening for atrial fibrillation above age 65 detects an asymptomatic subset at
      high risk of stroke.

PMID- 22964079
TI  - One year follow-up of patients with screen-detected metabolic syndrome in primary
      care: an observational study.
AB  - BACKGROUND: Early detection and appropriate treatment of metabolic syndrome
      (MetS) can modify cardiometabolic risk factors and prevent cardiovascular
      disease. Optimal screening outcomes require follow-up management of MetS.
      OBJECTIVE: To investigate the natural course of events in the first year after
      positive screening for MetS in primary care with regard to follow-up behavior,
      medication prescription and lifestyle changes. METHODS: Screening of 1721
      apparently healthy primary care patients (20-70 years old) detected 473 new MetS
      cases. These people were asked to contact their general practice for subsequent
      advice and treatment. Data about follow-up behavior of the screening participants
      and prescription of cardiovascular medication were collected from the electronic
      medical file, and changes in lifestyle were collected by the practice nurse.
      RESULTS: Of the 424 participants with screen-detected MetS for whom data about
      follow-up were available, 306 (72.2%) spontaneously contacted the practice.
      Antihypertensive, lipid-lowering and blood glucose-lowering medications were
      prescribed in 21.5%, 21.2% and 1.9% of the participants, respectively. Half of
      the participants for whom data about self-reported lifestyle changes were
      available reported to have increased their physical activity; 16.9% of the
      smokers quit smoking. Average weight loss was 2.1kg. CONCLUSIONS: Screening for
      MetS followed by the advice to contact the general practice for lifestyle
      counseling and treatment had a substantial spontaneous follow-up. Although the
      changes in physical activity, weight loss and smoking abstinence are promising,
      further research will have to demonstrate whether they are sustainable.

PMID- 22964081
TI  - Can innominate motion be used to identify persons with ankylosing spondylitis? A
      pilot study.
AB  - Innominate movements during hip abduction and external rotation have recently
      been described in healthy individuals. In the present study the aim was to
      determine whether these hip movement tests could discriminate altered movement
      patterns in people with specific pelvic girdle pain (PGP) disorder. This pilot
      study is the first step in determining the usefulness of prone hip abduction and
      external rotation in the differential diagnosis of PGP disorders. A cross
      sectional comparison between a convenient sample of 6 individuals who had been
      referred for exercise and advice following diagnosis of ankylosing spondylitis
      (AS) via a Medical/Rheumatological pathway and 18 healthy age and gender matched
      controls. Transverse and sagittal plane innominate motion was measured using a
      palpation and digitizing technique with a magnetic tracking device. Data analysis
      involved applying best-fit equations to the data and visual inspection of the
      produced graphs as well as conditional logistical regression for each test
      position to determine our ability to predict group association. Graphical
      comparisons demonstrate a distinction between the patients with AS and the
      healthy controls. Further, for all three hip conditions the innominate angle was
      a significant predictor of group association (p = 0.002 for AB, p = 0.005 for AB
      + ER and p = 0.007 for ER).

PMID- 22964082
TI  - Development and use of standardised data collection tools to support and inform
      musculoskeletal practice.
AB  - Clinicians all over the world are increasingly being faced with the need to
      demonstrate and account for the way in which clinical services are delivered and
      the quality of the delivery. It is also imperative to develop a comprehensive
      profile of who is accessing these services, who benefits from these services; how
      much these services cost in terms of clinicians time, the use of other healthcare
      resources and the effectiveness of interventions utilised in relation to quality
      outcomes. Clinicians are themselves keen to have mechanisms to identify what
      approaches are being utilised in their own practice setting, how they work best
      and how they can be improved from a professional development perspective. They
      are also anxious to improve their skills based on informed reflective practice
      and identify gaps in their knowledge and skills. This masterclass identifies how
      standardised data collection (SDC) tools can be utilised in practice to gather
      the information required in a robust, agreed and accessible way. It summarises a
      method of SDC tool development and gives some examples of how SDC has been
      implemented in physiotherapy National Health Services and in physiotherapy
      private practice in the United Kingdom. The global relevance is that increasingly
      all physiotherapy services are being held and will be accountable for the quality
      and equity of care. In addition clinicians can find it useful to have benchmarks
      with which to compare their own and their departmental performance in terms of
      clinical activities and outcomes.

PMID- 22964083
TI  - [Recovered sudden cardiac death associated with an early repolarization syndrome:
      case analysis and pratical aspects].
AB  - In this article, we report the case of a 61-year-old man who presented a cardiac
      arrest which has been resuscitated successfully. An early repolarization syndrome
      has been diagnosed by the ECG recorded the first 3 days after admission. This
      abnormality disappeared after that. The patient received an implantable
      cardioverter-defibrillator. Practical messages to the clinician concerning early
      repolarization are provided in this article.

PMID- 22964084
TI  - [Severe sick sinus syndrome associated with a Werner's syndrome].
AB  - A 39-year-old woman was explored for recurrent syncopes. She was already known
      for a Werner's syndrome with symptoms of aging disorders. The explorations
      revealed an episode of sinusal arrest. A pacemaker was implanted. This case
      emphasises the relation between Werner syndrome and the development of
      cardiovascular abnormalities. This pathology should be recalled in young patients
      with symptoms of aging disorders and cardiovascular abnormalities. Valvular
      abnormalities, myocardial infarction and stroke are the major complications of
      Werner's syndrome. This case indicates that a sick sinus syndrome is a rare but
      possible complication of Werner's syndrome.

PMID- 22964085
TI  - Biologically-based modeling insights in inhaled vapor absorption and dosimetry.
AB  - The lung is a route of entry and also a target site for inhaled vapors,
      therefore, knowledge of the total absorbed dose and/or the dose absorbed in each
      airway during inhalation exposure is essential. Vapor absorption characteristics
      result primarily from the fact that vapors demonstrate equilibrium/saturation
      behavior in fluids. Thus, during inhalation exposures blood and airway tissue
      vapor concentrations increase to a steady state value and increase no further no
      matter how long the exposure. High tissue concentrations can be obtained with
      highly soluble vapors, thus solubility, as measured by blood:air partition
      coefficient, is a fundamentally important physical/chemical characteristic of
      vapors. While it is classically thought that vapor absorption occurs only in the
      alveoli it is now understood that this is not the case. Soluble vapors can be
      efficiently absorbed in the airways themselves and do not necessarily penetrate
      to the alveolar level. Such vapors are more likely to injure the proximal than
      distal airways because that is the site of the greatest delivered dose. There are
      substantial species differences in airway vapor absorption between laboratory
      animals and humans making interpretation of laboratory animal inhalation toxicity
      data difficult. Airway absorption is dependent on vapor solubility and is
      enhanced by local metabolism and/or direct reaction within airway tissues. Modern
      simulation models that incorporate terms for solubility, metabolism, and reaction
      rate accurately predict vapor absorption patterns in both animals and humans and
      have become essential tools for understanding the pharmacology and toxicology of
      airborne vapors.

PMID- 22964087
TI  - Yerba mate (Ilex paraguariensis) enhances the gene modulation and activity of
      paraoxonase-2: in vitro and in vivo studies.
AB  - OBJECTIVE: Paraoxonase-2 (PON-2) is an intracellular antioxidant enzyme that can
      be modulated by polyphenols. The aim of this study was to verify whether yerba
      mate (Ilex paraguariensis), a plant species rich in phenolic compounds, modulates
      gene expression and the activity of PON-2 in macrophages in vitro and in
      monocytes from peripheral blood and monocyte-derived macrophages obtained after
      the ingestion of green or roasted yerba mate infusions by healthy subjects.
      METHODS: THP-1 macrophages were incubated with increasing amounts of yerba mate
      extracts or chlorogenic and caffeic acids (1-10 MUmol/L). The in vivo effects of
      yerba mate or water (control) intakes were evaluated acutely (2 h after
      ingestion) and in the short term (after daily ingestion for 7 d) in 20 healthy
      women. RESULTS: In general, there was no difference between the two kinds of
      yerba mate studied. Yerba mate extracts or chlorogenic acid at 1 and 3 MUmol/L
      increased PON-2 relative gene expression in THP-1 macrophages (P < 0.05), whereas
      higher concentrations (5 and 10 MUmol/L) increased the activity only. Caffeic
      acid induced PON-2 activity only. The acute ingestion of yerba mate infusions
      increased relative gene expression and PON-2 activity in monocytes (P < 0.05),
      whereas the consumption of yerba mate for 7 d increased PON-2 relative gene
      expression (P < 0.05) and had a tendency to increase PON-2 activity in monocytes
      and monocyte-derived macrophages. CONCLUSION: It is suggested that green or
      roasted yerba mate modulates positively the mRNA relative expression and activity
      of the PON-2 enzyme in monocytes and macrophages, which may prevent cellular
      oxidative stress.

PMID- 22964088
TI  - Apple polyphenol protects against cigarette smoke-induced acute lung injury.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complex chronic
      inflammatory disease involving oxidative stress as well as a wide variety of
      cells activated from smoking cigarettes. There have been disappointingly few
      therapeutic advances in drug therapy for COPD. Plant polyphenols have been the
      topic of much research regarding their antioxidant activities and
      antiinflammatory and immunomodulatory effects. In the present study, we ask
      whether apple polyphenol provides protection against cigarette smoke (CS)-induced
      acute lung injury. METHODS: ICR mice were exposed to CS for 4 d with increasing
      exposure time for up to 6 h per day to elicit epithelial cells injury. One hour
      before smoke exposure, mice were treated with apple polyphenol (APP) by gavage;
      all examinations were performed 18 h after the last CS exposure. RESULTS: APP at
      30, 100, or 300 mg not only significantly dose-dependently reduced the CS-induced
      accumulation of inflammatory cells and gene/protein expression of proinflammatory
      factors both in the lung and in bronchoalveolar lavage fluid, but also
      significantly reversed oxidative stress in the lungs. Additionally, treatment
      with APP also significantly regulated the CS-induced imbalance of matrix
      metalloproteinases-9/tissue inhibitor of metalloproteinase-1 expression in the
      lungs. To investigate further the possible signaling pathway of APP effects, we
      examined protein expression of p-P38 MAPK by immunohistochemistry that found
      treatment with APP significantly decreased the CS-induced increases of p-P38
      expression in the lungs. CONCLUSION: Taken together, APP may be a potential
      dietary nutrient supplement agent to improve quality of life of COPD patients by
      inhibiting CS-exposed acute lung injury via P38 MAPK signaling pathway.

PMID- 22964086
TI  - SNPing cancer in the bud: microRNA and microRNA-target site polymorphisms as
      diagnostic and prognostic biomarkers in cancer.
AB  - MicroRNAs are master regulators of gene expression and control many biological
      pathways such as cell growth, differentiation and apoptosis. Deregulation of
      microRNA expression and activity results in a myriad of diseases including
      cancer. Recently, several reports have indicated that single nucleotide
      polymorphisms (SNPs) in microRNAs and microRNA-target sites impact microRNA
      biology and associate with cancer risk, treatment response and outcome. In this
      review we will describe these findings and discuss the possible future of
      utilizing these SNPs as diagnostic and prognostic markers in the clinic.

PMID- 22964089
TI  - Three-dimensional measurement method of arthritic glenoid cavity morphology:
      feasibility and reproducibility.
AB  - INTRODUCTION: Glenoid component loosening is the main complication of total
      shoulder arthroplasty. Better knowledge of the arthritic glenoid cavity anatomy
      can help in developing new implants and techniques. The goal of this study was to
      describe and validate the reproducibility of a CT scan-based, 3D measurement
      method used to describe various parameters characterizing arthritic glenoid
      cavity morphology. MATERIALS AND METHODS: Twelve CT scans and 29 CT arthrogram
      were evaluated. These scans were taken from 41 patients with glenohumeral
      osteoarthritis who received an anatomical shoulder prosthesis. A 3D
      reconstruction of the scapula was performed based on the DICOM files. Following
      the 3D volume acquisition, points on the glenoid articular surface were manually
      extracted by three observers, each one three times, allowing one week between
      readings, to determine the inter- and intra-observer reproducibility. The
      intraclass correlation coefficient (ICC) was calculated on five 3D parameters
      that were automatically calculated: glenoid height, glenoid width, height at
      maximum width glenoid version and radius of the articular surface best-fit
      sphere. RESULTS: The intra-observer and inter-observer ICC were 0.91 to 0.99, and
      0.95 to 0.99, respectively. DISCUSSION: This study is the first to report on a
      reproducible 3D measurement method, based on CT scans, for the arthritic glenoid
      cavity, which derives the joint radius of curvature among other morphology
      parameters. These 3D measurements are advantageous because they are free of
      problems related to patient positioning in the CT scanner and to the choice of
      slices, which limits the accuracy of measurements made on slices from 2D CT
      scans. Three-dimensional methodology similar to ours has been validated on
      healthy glenoids. CONCLUSION: This study confirms the reliability and good
      reproducibility of our method, which allows us to extend this method to a larger
      patient cohort and adapt this automated technology to preoperative planning
      software.

PMID- 22964090
TI  - Electrospinning preparation and drug delivery properties of Eu3+/Tb3+ doped
      mesoporous bioactive glass nanofibers.
AB  - Luminescent Eu(3+)/Tb(3+) doped mesoporous bioactive glass nanofibers (MBGNFs)
      with average diameter of 100-120 nm were fabricated by electrospinning method.
      Pluronic P123 and N-cetyltrimethylammonium bromide (CTAB) were used as co
      surfactants to generate porous structure of the nanofibers. N(2) adsorption
      desorption measurement reveals that the MBGNF:Eu(3+) have a surface area of 188
      m(2) g(-1), a pore volume of 0.246 cm(3) g(-1) and average pore size of 4.17 nm,
      and the MBGNF:Tb(3+) have a surface area of 171 m(2) g(-1), a pore volume of
      0.186 cm(3) g(-1) and average pore size of 3.65 nm. Photoluminescence
      measurements reveal that the MBGNF:Eu(3+) show strong red emission dominated by
      the (5)D(0)->(7)F(2) transition of Eu(3+) at 614 nm with a lifetime of 1.356 ms,
      and MBGNF:Tb(3+) show strong green emission dominated by the (5)D(4)->(7)F(5)
      transition of Tb(3+) at 544 nm with a lifetime of 1.982 ms. The biocompatibility
      tests on L929 fibroblast cells using MTT assay reveal low cytotoxicity of MBGNF.
      These luminescent nanofibers show sustained release properties for ibuprofen
      (IBU) in vitro. The emission intensities of Eu(3+) in the drug delivery 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- 22964091
TI  - Surface phase separation, dewetting feature size, and crystal morphology in thin
      films of polystyrene/poly(epsilon-caprolactone) blend.
AB  - Thin films of polystyrene (PS)/poly(epsilon-caprolactone) (PCL) blends were
      prepared by spin-coating and characterized by tapping mode force microscopy
      (AFM). Effects of the relative concentration of PS in polymer solution on the
      surface phase separation and dewetting feature size of the blend films were
      systematically studied. Due to the coupling of phase separation, dewetting, and
      crystallization of the blend films with the evaporation of solvent during spin
      coating, different size of PS islands decorated with various PCL crystal
      structures including spherulite-like, flat-on individual lamellae, and flat-on
      dendritic crystal were obtained in the blend films by changing the film
      composition. The average distance of PS islands was shown to increase with the
      relative concentration of PS in casting solution. For a given ratio of PS/PCL,
      the feature size of PS appeared to increase linearly with the square of PS
      concentration while the PCL concentration only determined the crystal morphology
      of the blend films with no influence on the upper PS domain features. This is
      explained in terms of vertical phase separation and spinodal dewetting of the PS
      rich layer from the underlying PCL rich layer, leading to the upper PS dewetting
      process and the underlying PCL crystalline process to be mutually independent.

PMID- 22964092
TI  - Synthesis of hollow and nanoporous gold/platinum alloy nanoparticles and their
      electrocatalytic activity for formic acid oxidation.
AB  - In this work, hollow Au/Pt alloy nanoparticles (NPs) with porous surfaces were
      synthesized in a two-step procedure. In the first step, tri-component Ag/Au/Pt
      alloy NPs were synthesized through the galvanic replacement reaction between Ag
      NPs and aqueous solutions containing a mixture of HAuCl(4) and H(2)PtCl(4). In
      the second step, the Ag component was selectively dealloyed with nitric acid
      (HNO(3)), resulting in hollow di-component Au/Pt alloy NPs with a porous surface
      morphology. The atomic ratio of Au to Pt in the NPs was easily tunable by
      controlling the molar ratio of the precursor solution (HAuCl(4) and H(2)PtCl(6)).
      Hollow, porous Au/Pt alloy NPs showed enhanced catalytic activity toward formic
      acid electrooxidation compared to the analogous pure Pt NPs. This improved
      activity can be attributable to the suppression of CO poisoning via the
      "ensemble" effect.

PMID- 22964093
TI  - Microfluidic preparation and self diffusion PFG-NMR analysis of monodisperse
      water-in-oil-in-water double emulsions.
AB  - Monodisperse water-in-oil-in-water (WOW) double emulsions have been prepared
      using microfluidic glass devices designed and built primarily from off the shelf
      components. The systems were easy to assemble and use. They were capable of
      producing double emulsions with an outer droplet size from 100 to 40 MUm.
      Depending on how the devices were operated, double emulsions containing either
      single or multiple water droplets could be produced. Pulsed-field gradient self
      diffusion NMR experiments have been performed on the monodisperse water-in-oil-in
      water double emulsions to obtain information on the inner water droplet diameter
      and the distribution of the water in the different phases of the double emulsion.
      This has been achieved by applying regularization methods to the self-diffusion
      data. Using these methods the stability of the double emulsions to osmotic
      pressure imbalance has been followed by observing the change in the size of the
      inner water droplets over time.

PMID- 22964094
TI  - CdS and CdSe quantum dots subsectionally sensitized solar cells using a novel
      double-layer ZnO nanorod arrays.
AB  - We report a novel approach for synthesizing CdS and CdSe quantum dots
      subsectionally sensitized double-layer ZnO nanorods for solar cells, which are
      comprised of CdS QDs-sensitized bottom-layer ZnO NRs and CdSe QDs-sensitized top
      layer ZnO NRs. X-ray diffraction study and scanning electron microscopy analysis
      indicate that the solar cells of subsectionally sensitized double-layer ZnO NRs,
      which are the hexagonal wurtzite crystal structure, have been successfully
      achieved. The novel structure enlarged the range of absorbed light and enhanced
      the absorption intensity of light. The I-V characteristics show that the double
      layer structure improved both the current density (J(sc)) and fill factor (FF) by
      50%, respectively, and power conversion efficiency (eta) was increased to twice
      in comparison with the CdS QDs-sensitized structure.

PMID- 22964095
TI  - Controllable preparation and formation mechanism of monodispersed silica
      particles with binary sizes.
AB  - Monodispersed silica particles with bimodal size distribution were successfully
      prepared through adding an ethanol (EtOH) solution containing
      tetraethylorthosilicate (TEOS) dropwise into an ammonia EtOH solution at a
      constant low rate. The effects of the reaction parameters such as ammonia/ethanol
      ratio, feeding rate of TEOS solution, reaction temperature, and time on the size
      and size distribution of the as-obtained particles were investigated. Based on
      these phenomena, a modified LaMer model of nucleation and growth mechanism was
      proposed to reasonably explain the formation of the as-obtained silica particles
      with bimodal size distribution. The as-prepared monodispersed silica particles
      with bimodal size distribution can be directly fabricated into binary colloidal
      crystals with small particles surrounding large particles by evaporation-induced
      cooperative self-assembly. This suggests that the method reported here provides a
      straightforward and effective route to the in situ fabrication of novel binary
      colloidal crystals and their replicated patterns in one reaction system.

PMID- 22964096
TI  - Evaluation of lay health workers' needs to effectively support anti-tuberculosis
      treatment adherence in Malawi.
AB  - OBJECTIVE: To identify barriers and facilitators to efforts by lay health workers
      (LHWs) to support anti-tuberculosis treatment adherence in Malawi to inform the
      design of a knowledge translation intervention for improving adherence. DESIGN:
      Qualitative study utilizing focus groups  and interviews conducted with LHWs
      providing tuberculosis (TB) care in Zomba District, Malawi. RESULTS: Participants
      identified lack of knowledge, both general (understanding of TB and its
      treatment) and job-specific (understanding of tasks such as completion of
      treatment forms), as the  key barrier to LHWs in their role as adherence
      supporters. Lack of knowledge among LHWs providing TB care was reported to lead
      to a lack of confidence, conflicting messages given to patients, poor
      interactions with patients and errors in documentation. In addition to lack of
      knowledge, a number  of system barriers were identified as limiting LHWs' ability
      to function optimally, including a lack of physical resources, workload,
      communication delays and ineffective guardians. CONCLUSION: Our findings suggest
      a gap between LHW knowledge and their responsibilities as adherence supporters. 
      The results have informed the development of an educational outreach intervention
      and point-of-care tool, to be evaluated in a randomized trial in Zomba District.

PMID- 22964097
TI  - A comparison of the musculoskeletal assessments of the shoulder girdles of
      professional rugby players and professional soccer players.
AB  - OBJECTIVE: To identify posture types that exist in professional rugby players,
      and compare them with a population of non-overhead athletes in order to identify
      possible relationships towards the potential for shoulder injuries. DESIGN:
      Observational design Setting: Sports Medicine Clinic Participants: Convenience
      sample Methodology: Static assessment of posture was carried out in standing,
      active and passive range of glenohumeral motion, and isometric strength was
      carried out in accordance with previously recorded protocols. INTERVENTIONS: Nil
      Outcome Measures: Observational classification of posture, active and passive
      range of glenohumeral joint range of motion, isometric strength of selected
      muscle groups, selected muscle flexibility and Hawkins and Neer impingement
      tests. RESULTS: There was a significant difference on range of motion between the
      two groups (0.025-0.000), isometric middle (0.024-0.005), and lower trapezius
      (0.01-0.001). CONCLUSION: There were significant differences between strength and
      flexibility of muscles around the shoulder girdle between professional rugby
      players and a control group of professional non-overhead athletes.

PMID- 22964098
TI  - Chronic complications in patients with newly diagnosed type 2 diabetes.
AB  - INTRODUCTION: The sly start of type 2 diabetes (DM2) very often complicates the
      patient before diagnosis. An early diagnosis of diabetes is strongly stressed
      nowadays so as to avoid or retard the progression of chronic complications. But
      the same emphasis is not put on the urgency of the diagnosis of these
      complications, at the same time as diabetes is diagnosed. If we consider that
      around 50% of type 2 diabetics are not aware of their condition, the problem of
      chronic complications of varied severity in them needs special consideration.
      OBJECTIVE: The present study was designed in order to evaluate the presence of
      chronic complications and their evolutive stage in our population. PATIENTS AND
      METHOD: Three hundred and two newly diagnosed diabetic patients (NDD) underwent
      full clinical examination and laboratory evaluation within 30 days of diagnosis.
      Diagnostic procedures and tests were standardized for each complication. RESULTS:
      The mean age of the sample was 53+/-10 years (range, 24-77), with no difference
      between sexes. Complications were present in 156 patients (51.7%); 70 (44.9%) had
      one complication and 86 (55.1%) had 2 or more. Hypertension (HTA) was present in
      192 (63.6%) NDD, 38.6% had coronary heart disease (by Minnesota Code). Among
      lipid alterations, low high-density lipoprotein cholesterol was the most frequent
      (34.6%). Microvascular complications were prevalent both in women and men, in
      decreasing order: neuropathy (27.5%), nephropathy (20.2%), retinopathy (17.9%).
      Taking into account the severity of complications, retinopathy showed
      preponderance in evolutive stage. The silent myocardial infraction seems to be a
      more frequent pathology than expected (17.7%). CONCLUSIONS: It must be stressed
      the need for identification of chronic complications immediately after the
      diagnosis of DM2.

PMID- 22964099
TI  - Use of anthropometric measures to predict insulin resistance.
AB  - OBJECTIVE: Obesity is closely related to insulin-resistance (IR) but it is
      evaluated differently in the diverse definitions of the metabolic syndrome. The
      objective of this study was to verify the utility of different anthropometric
      measures to predict IR and to evaluate the best cut-off points. SUBJECTS AND
      METHOD: We performed a cross-sectional study of the general population aged 40 to
      70 years old (n=2,143); a simple random sample of 305 non-diabetic persons was
      obtained. Sociodemographic data, physical examination and routine biochemical
      analysis with insulinemia were obtained. IR was defined by a HOMA index
      (Homeostasis Model Assessment) >=2.9. To obtain the best variables to predict IR,
      a forward stepwise logistic regression was performed. Subsequently, a logistic
      equation was constructed and its predictive capacity was compared with the
      different anthropometric variables by the area under the ROC (receiver-operating
      characteristic) curve (AUC). The best cut-off points were established according
      to the Youden index. RESULTS: Body mass index (BMI) and the waist/hip ratio *100
      were entered into the model, but age, sex, waist, hip and body surface were not.
      The logistic equation found: p(RI)=1/1+exp{-[-14.295]-[0.234*IMC]
      [0.07*(waist/hip*100)]} showed good adjustment, and the probability calculated on
      the basis of this equation showed the greatest AUC overall and in both sexes,
      followed in women by BMI and by waist measurement in men, but without significant
      differences. CONCLUSIONS: No significant differences were found between the BMI,
      waist or hip measurements and the logistic model to predict IR.

PMID- 22964100
TI  - Alignment of the Kubler-Ross grief cycle phases with the process of adaptation to
      type 1 diabetes mellitus.
AB  - OBJECTIVE: To understand the process of adaptation to type 1 diabetes mellitus
      (DM1) and analyze its alignment with the grief cycle phases described by Kubler
      Ross. SUBJECTS AND METHOD: We performed an ethnographic study through in-depth
      interviews with 20 patients, 10 relatives and 12 health professionals (6
      physicians and 6 nurses). For the analysis, the Miles and Huberman qualitative
      data analysis model was used. RESULTS: Patients diagnosed with DM1 and their
      families face a loss of lifestyle and of the objects, real or imaginary, of their
      previous life. Patients and relatives experience emotional reactions that in some
      cases can be similar to the grief cycle phases described by Kubler-Ross for
      terminal diseases (denial, anger, bargaining, depression and acceptance).
      However, there are some differences depending on personal and psycho-social
      factors. Health professionals tend to relate low adherence to denial of the
      disease, but some patients feel threatened by the demands of treatment and
      control and their effects on their quality of life, and consciously choose not to
      follow recommendations. It is more realistic to talk about disease adaptation
      than acceptance, since the loss processes are ongoing and patients must
      reconstruct their identity according to their situation. The grief cycle also
      affects the family and may differ from that of the patient in its duration,
      intensity and assessment of problems. CONCLUSIONS: Adaptation is a complex
      process in which many variables intervene. There are observable differences among
      the mechanisms used by each specific individual. Healthcare professionals, and
      specifically nurses, should consider the multiple psycho-social dimensions of
      chronic disease.

PMID- 22964101
TI  - Hormone assays: some aspects that endocrinologists should know.
AB  - Since the pioneering works of Yalow and Berson that introduced radioimmunoassays
      (RIA), hormone assays have been developed gradually, with improvements in all
      aspects of their design, from immunoradiometric assays to automatization.
      Examples of this evolution are the thyrotropin (TSH) and parathyroid (PTH)
      assays. Despite the strong accuracy and reliability of currently used hormone
      assays, some limitations should be reviewed, such as interference by
      autoantibodies, heterophile antibodies or macroprolactin and the hook effect.

PMID- 22964102
TI  - The clinical laboratory and dyslipidemia.
AB  - The prevalence of dyslipidemia (alterations in lipoprotein metabolism) as a risk
      factor for cardiovascular disease continues to rise. Determination of circulating
      levels of lipids, lipoproteins and related proteins allows the diagnosis,
      treatment and followup of the various types of dyslipidemia. However, numerous
      factors influence the concentration of these constituents in the circulation.
      These factors depend both on the individual (habits, physical characteristics,
      presence of other risk factors) and on the sample and analytical methods employed
      and must be taken into account when assessing and interpreting laboratory
      results. Similarly, the cause of the different forms of dyslipidemia may lie not
      only in environmental but also in genetic factors. Consequently, the inclusion of
      genetic tests in the diagnosis of dyslipidemia is increasingly frequent.

PMID- 22964103
TI  - Primary hyperparathyroidism due to parathyroid carcinoma associated with
      pulmonary embolism.
AB  - Parathyroid carcinoma (PC) is an uncommon disease affecting 0.5-5% of all
      patients with primary hyperparathyroidism. PC is characterized by the association
      of severe symptoms of hypercalcemia, high serum calcium and parathyroid hormone
      (PTH) concentrations and a palpable neck mass. Definitive diagnosis can only be
      made by histological study after surgery. We report the case of a 77-year-old man
      admitted to our hospital due to pulmonary embolism and hypercalcemia. The patient
      was initially diagnosed with primary hyperparathyroidism, but displayed the
      atypical clinical features described above. Due to clinical suspicion of PC, a
      surgical procedure was carried out. Diagnosis of parathyroid carcinoma was
      confirmed by histopathologic study.

PMID- 22964104
TI  - Sellar xanthogranuloma.
AB  - We report the case of a 16-year-old girl with a history of idiopathic precocious
      puberty and normal results on pituitary imaging scan. Ten years later, a new
      cranial magnetic resonance imaging scan was performed due to worsening of
      episodes resembling Horton's headache and a lesion suggestive of pituitary
      bleeding was detected. The headaches diminished with glucocorticoid
      administration but a severe complication, steroid psychosis, occurred. Surgical
      treatment and pathological study of the lesion led to the differential diagnosis
      between craniopharyngyoma and xanthogranuloma of the sella turcica. The clinical
      progression of the tumor (not visualized 10 years previously), together with
      preservation of pituitary and visual function both before and after surgery,
      gross total removal of the tumor (difficult to achieve with craniopharyngioma)
      and the absence of recurrence provide strong support for the diagnosis of
      xanthogranuloma of the sella turcica.

PMID- 22964105
TI  - Population attributable fractions of farm vector tick (Rhipicephalus
      appendiculatus) presence on Theileria parva infection seroprevalence under
      endemic instability.
AB  - The primary objective of this study was to assess the impact of Rhipicephalus
      appendiculatus tick presence (exposure variable) on Theileria parva infection
      seroprevalence (outcome variable) in a group of cattle belonging to a farm using
      population attributable fractions (PAF). The analyses were based on a
      representative sample of 80 traditional smallholder mixed farms. The farms were
      selected by first stratifying the population administratively and implementing a
      multistage random sampling in Mbeere district in Kenya. The PAFs were estimated
      using the stratified, Bruzzi, and sequential partitioned PAF approaches. A
      secondary objective was, thus, to evaluate the impact of the approaches on the
      PAF estimates. The stratified and Bruzzi approaches estimated proportion of T.
      parva infection cases directly attributable to the exposure after controlling for
      confounding by agro-ecological zone (AEZ). The sequential partitioned PAF
      approach estimated a PAF associated with exposure after adjusting for any effect
      that the AEZ may have had by influencing the prevalence of the exposure. All
      analyses were carried out at the farm level where a farm was classified as
      infested if the tick was found on cattle on a farm, and infected if at least one
      animal on a farm was positive for T. parva antibodies. Variance estimation for
      PAFs was implemented using 'delete-a-group' jackknife re-sampling method. The
      stratified PAF (26.7% [95% CI: 9.0%, 44.4%]) and Bruzzi PAF (26.4% [95% CI: 9.6%,
      43.2%]) were consistent in estimating a relatively low impact of farm vector tick
      presence with a relatively high level of uncertainty. The partitioned PAF (15.5%
      [95% CI: 1.5%, 29.6%]) suggested that part of the impacts estimated using the
      stratified PAF and Bruzzi approaches was driven by AEZ effects. Overall, the
      results suggested that under endemic instability in Mbeere district, (1) presence
      of R. appendiculatus was not a good indicator of T. parva infection occurrence on
      a farm; (2) ecological variation could play a role in determining infection
      impacts. This study provides a preliminary basis for evaluating the potential
      value and utility of estimating PAFs for variables amenable to control in tick
      borne diseases (TBDs) epidemiological studies.

PMID- 22964106
TI  - Limitations of reliance on specific IgE for epidemiologic surveillance of food
      allergy.

PMID- 22964107
TI  - Filaggrin loss-of-function mutations do not predict food allergy over and above
      the risk of food sensitization among infants.

PMID- 22964108
TI  - Smad2 is involved in the apoptosis of murine gingival junctional epithelium
      associated with inhibition of Bcl-2.
AB  - OBJECTIVE: Gingival junctional epithelium (JE) actively contributes to the
      homeostasis of the periodontium. Altered activation of TGF-beta signalling is
      implicated in the epithelium from chronic periodontitis. However, little is known
      about the effects of TGF-beta signalling on the JE. In this study, we
      investigated the relationship between Smad2, which plays an important role in
      mediating TGF-beta signal, and induction of apoptosis in the JE. METHODS: K14
      Smad2 transgenic mice were used to observe the effect of over-expression of Smad2
      driven by CK14 promoter in the JE. We performed TUNEL technique to evaluate the
      epithelial apoptosis. Expression of apoptosis related genes was examined using
      real-time PCR and immunofluorescence. RESULTS: K14-Smad2 mice showed an increased
      number of phospho-Smad2 positive JE cells associated with an increase in TGF
      beta1 expression. K14-Smad2 mice have a significantly higher percentage of TUNEL
      positive cells in the JE. Immunofluorescence double labelling revealed that TUNEL
      positive cells showed immunoreactivity to phospho-Smad2. Real-time PCR analysis
      of apoptosis related gene expression provided evidence of lower expression of Bcl
      2 in the gingival tissue from K14-Smad2 mice. There was a strong positive
      reaction for Bcl-2 protein in the junctional epithelium of wild type mice, while
      the gingival tissue of K14-Smad2 transgenic mice had only a faint signal for Bcl
      2. CONCLUSIONS: The present study provided evidence that Smad2 plays a crucial
      role in the induction of apoptosis in gingival JE through inhibition of Bcl-2.

PMID- 22964109
TI  - The effects of lesion baseline characteristics and different Sr:Ca ratios in
      plaque fluid-like solutions on caries lesion de- and remineralization.
AB  - This study investigated the effects of lesion baseline characteristics and
      different strontium (Sr) to calcium (Ca) ratios in plaque fluid-like solutions
      (PF) on lesion de- and remineralization. Caries lesions were formed in enamel
      using three protocols: methylcellulose acid gel (MeC) and partially saturated
      lactic acid solutions containing carboxymethylcellulose (CMC) or not (SOLN).
      Lesions were exposed to PF with four distinct Sr:Ca molar ratios (0:1/3:1:3), but
      otherwise identical composition and total Sr+Ca molarity, for seven days. Lesions
      were characterized using transverse microradiography (TMR) at baseline and post
      treatment. At baseline, MeC and CMC had similar integrated mineral loss values,
      whereas SOLN lesions were more demineralized. All lesions showed significant
      differences in their mineral distributions, with CMC and SOLN having lower R
      values (integrated mineral loss to lesion depth ratio) than MeC. Post-PF
      exposure, no interaction was found between lesion type and Sr:Ca ratio. Within
      lesion type, MeC demineralized, whereas CMC and SOLN exhibited some
      remineralization, with the differences between MeC and the other lesion types
      being of statistical significance. Within Sr:Ca ratio, the 1:3 ratio exhibited
      some remineralization whereas other groups tended to demineralize. Only the
      difference between groups SrCa1/3 and SrCa0 was of statistical significance. In
      summary, both lesion baseline characteristics and Sr:Ca ratio were shown to
      effect lesion de- and remineralization. Under the conditions of the study, high-R
      lesions are more prone to demineralize under PF-like conditions than low-R
      lesions. In addition, partial Sr substitution for Ca in PF was shown to enhance
      lesion remineralization.

PMID- 22964110
TI  - Regulation of the innate immune system by ubiquitin and ubiquitin-like modifiers.
AB  - Detection of invading pathogens by pattern recognition receptors (PRRs) is
      crucial for the activation of the innate immune response. These sensors signal
      through intertwining signaling cascades which result in the expression of pro
      inflammatory cytokines and type I interferons. Conjugation, or binding, of
      ubiquitin and ubiquitin-like modifiers (UBLs) to a plethora of immune signaling
      molecules forms a common theme in innate immune regulation. Numerous E3 ligases
      and deubiquitylating enzymes (DUBs) actively modify signaling components in order
      to achieve a balanced activation of the innate immune system. This review will
      discuss how this balance is achieved and which questions remain regarding innate
      immune regulation by ubiquitin and UBLs.

PMID- 22964111
TI  - Schizotypal traits in adolescents: links to family history of psychosis and
      psychological distress.
AB  - OBJECTIVE: Studies in the general population report that unusual subjective
      experiences are relatively common. Such experiences have been conceptualized
      either as extreme personality traits or as vulnerability markers for psychosis,
      and often grouped under the expression "schizotypal experiences". This study
      investigates the heterogeneity of schizotypal traits using factor and latent
      class analysis. METHODS: One thousand and thirty-two adolescents were recruited
      for this study. Schizotypal experiences were assessed with the Oxford-Liverpool
      Inventory of Feelings and Experiences (O-LIFE); psychological distress was
      assessed with the General Health Questionnaire (GHQ). Confirmatory Factorial
      Analysis (CFA) and Latent Class Analysis (LCA) were performed on the O-LIFE and
      on the association with the GHQ and demographic variables. RESULTS: CFA
      replicated the original 4-factor structure of the O-LIFE. Three latent classes
      (LC) of schizotypal features were identified: participants in LC1 (26% of the
      total sample) showed minimal level of item endorsement; LC2 accounted for 52% of
      the sample and showed overall higher item endorsement compared to LC1, especially
      for disorganization and positive signs of schizotypy, but not for negative
      affective items. LC3 (22%) showed an overall higher level of item endorsement
      across schizotypal dimensions, and positive association with psychological
      distress and family history of psychosis. DISCUSSION: Different latent class of
      schizotypal features can be empirically defined in adolescent community samples.
      The most extreme class is defined not only by a profile of higher positive
      replies to the items, but also by anhedonia, high psychological distress, and
      family history of psychosis. These findings can inform prevention research in
      schizophrenia.

PMID- 22964112
TI  - Optimization and application of subtype specific polymerase chain reaction for
      detection and identification of mixed subtypes of hepatitis C virus in patients
      with renal disease.
AB  - The main objective of the study is to optimize a subtype specific polymerase
      chain reaction (PCR) for identification of hepatitis C virus (HCV) subtypes in
      patients with renal disease. Thirty two peripheral blood specimens obtained from
      28 patients (post renal transplant N=14, chronic kidney disease N=14) were
      subjected to HCV viral load determination followed by genotyping analysis. Based
      on the mixed genotypes and subtypes (>one subtype) obtained by type specific PCR,
      specific patterns from Pattern I through Pattern X were assigned. All the 32
      peripheral blood specimens revealed mixed HCV subtype patterns (>one subtype).
      The detection of Pattern I in 12 (42.8%) out of 28 patients was statistically
      significant (Chi square test, P value<0.001). HCV subtyping assay developed using
      stringent thermal profile revealed the presence of mixed subtype patterns (>one
      subtype) which is for the first time being reported in literature.

PMID- 22964113
TI  - Impact of a reduced red and processed meat dietary pattern on disease risks and
      greenhouse gas emissions in the UK: a modelling study.
AB  - OBJECTIVES: Consumption of red and processed meat (RPM) is a leading contributor
      to greenhouse gas (GHG) emissions, and high intakes of these foods increase the
      risks of several leading chronic diseases. The aim of this study was to use newly
      derived estimates of habitual meat intakes in UK adults to assess potential co
      benefits to health and the environment from reduced RPM consumption. DESIGN:
      Modelling study using dietary intake data from the National Diet and Nutrition
      Survey of British Adults. SETTING: British general population. METHODS:
      Respondents were divided into fifths by energy-adjusted RPM intakes, with
      vegetarians constituting a sixth stratum. GHG emitted in supplying the diets of
      each stratum was estimated using data from life-cycle analyses. A feasible
      counterfactual UK population was specified, in which the proportion of
      vegetarians measured in the survey population doubled, and the remainder adopted
      the dietary pattern of the lowest fifth of RPM consumers. OUTCOME MEASURES:
      Reductions in risks of coronary heart disease, diabetes and colorectal cancer,
      and GHG emissions, under the counterfactual. RESULTS: Habitual RPM intakes were
      2.5 times higher in the top compared with the bottom fifth of consumers. Under
      the counterfactual, statistically significant reductions in population aggregate
      risks ranged from 3.2% (95% CI 1.9 to 4.7) for diabetes in women to 12.2% (6.4 to
      18.0) for colorectal cancer in men, with those moving from the highest to lowest
      consumption levels gaining about twice these averages. The expected reduction in
      GHG emissions was 0.45 tonnes CO(2) equivalent/person/year, about 3% of the
      current total, giving a reduction across the UK population of 27.8 million
      tonnes/year. CONCLUSIONS: Reduced consumption of RPM would bring multiple
      benefits to health and environment.

PMID- 22964114
TI  - The possible absence of a healthy-worker effect: a cross-sectional survey among
      educated Japanese women.
AB  - OBJECTIVES: Despite being highly educated in comparison with women in other
      member countries of the Organisation for Economic Cooperation and Development,
      Japanese women are expected to assume traditional gender roles, and many dedicate
      themselves to full-time housewifery. Women working outside the home do so under
      poor conditions, and their health may not be better than that of housewives. This
      study compared the self-rated health status and health behaviours of housewives
      and working women in Japan. DESIGN: Cross-sectional survey. SETTING: A national
      university in Tokyo with 9864 alumnae. PARTICIPANTS: A total 1344 women who
      graduated since 1985 and completed questionnaires in an anonymous mail-based
      survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Health anxiety and satisfaction,
      receipt of health check-ups, eating breakfast, smoking, and sleep problems
      according to job status and family demands: housewives (n=247) and working women
      with (n=624) and without (n=436) family demands. ORs were used for risk
      assessment, with housewives as a reference. RESULTS: After adjustment for
      satisfaction with present employment status and other confounding factors,
      working women were more likely than housewives to feel health anxiety (with
      family demands, OR: 1.68, 95% CI1.10 to 2.57; without family demands, OR: 3.57,
      95% CI 2.19 to 4.50) and health dissatisfaction (without family demands, OR:
      3.50, 95% CI 2.35 to 5.21); they were also more likely than housewives to eat an
      insufficient breakfast (with family demands, OR: 1.91, 95% CI 1.22 to 3.00;
      without family demands, OR: 4.02, 95% CI 2.47 to 6.57) and to have sleep problems
      (ORs: 2.08 to 4.03). CONCLUSIONS: No healthy-worker effect was found among
      Japanese women. Housewives, at least those who are well educated, appear to have
      better health status and health-related behaviours than do working women with the
      same level of education.

PMID- 22964116
TI  - Correction.

PMID- 22964115
TI  - BCG vaccination in England since 2005: a survey of policy and practice.
AB  - OBJECTIVE: Assess the current BCG vaccination policies and delivery pathways for
      immunisation in Primary Care Trusts (PCTs) in England since the 2005 change in
      recommendations. DESIGN: A survey of key informants across PCTs using a
      standardised, structured questionnaire. SETTING: 152 PCTs in England. RESULTS:
      Complete questionnaires were returned from 127 (84%) PCTs. Sixteen (27%) PCTs
      reported universal infant vaccination and 111 (73%) had selective infant
      vaccination. Selective vaccination outside infancy was also reported from 94
      (74%) PCTs. PCTs with selective infant policy most frequently vaccinated on
      postnatal wards (51/102, 50%), whereas PCTs with universal infant vaccination
      most frequently vaccinated in community clinics (9/13, 69%; p=0.011). To identify
      and flag up eligible infants in PCTs with targeted infant immunisation, those who
      mostly vaccinate on postnatal wards depend on midwives and maternity records,
      whereas those who vaccinate primarily in the community rely more often on various
      healthcare professionals. CONCLUSIONS: Targeted infant vaccination has been
      implemented in most PCTs across the UK. PCTs with selective infant vaccination
      provide BCG vaccine via a greater variety of healthcare professionals than those
      with universal infant vaccination policies. Data on vaccine coverage would help
      evaluate the effectiveness of delivery. Interruptions of delivery noted here
      emphasise the importance of not just an agreed, standardised, local pathway, but
      also a named person in charge.

PMID- 22964117
TI  - Correction.

PMID- 22964118
TI  - Correction.

PMID- 22964119
TI  - Correction.

PMID- 22964120
TI  - Rates of obstetric intervention among low-risk women giving birth in private and
      public hospitals in NSW: a population-based descriptive study.
AB  - OBJECTIVES: To compare the risk profile of women giving birth in private and
      public hospitals and the rate of obstetric intervention during birth compared
      with previous published rates from a decade ago. DESIGN: Population-based
      descriptive study. SETTING: New South Wales, Australia. PARTICIPANTS: 691 738
      women giving birth to a singleton baby during the period 2000 to 2008. MAIN
      OUTCOME MEASURES: Risk profile of women giving birth in public and private
      hospitals, intervention rates and changes in these rates over the past decade.
      RESULTS: Among low-risk women rates of obstetric intervention were highest in
      private hospitals and lowest in public hospitals. Low-risk primiparous women
      giving birth in a private hospital compared to a public hospital had higher rates
      of induction (31% vs 23%); instrumental birth (29% vs 18%); caesarean section
      (27% vs 18%), epidural (53% vs 32%) and episiotomy (28% vs 12%) and lower normal
      vaginal birth rates (44% vs 64%). Low-risk multiparous women had higher rates of
      instrumental birth (7% vs 3%), caesarean section (27% vs 16%), epidural (35% vs
      12%) and episiotomy (8% vs 2%) and lower normal vaginal birth rates (66% vs 81%).
      As interventions were introduced during labour, the rate of interventions in
      birth increased. Over the past decade these interventions have increased by 5%
      for women in public hospitals and by over 10% for women in private hospitals.
      Among low-risk primiparous women giving birth in private hospitals 15 per 100
      women had a vaginal birth with no obstetric intervention compared to 35 per 100
      women giving birth in a public hospital. CONCLUSIONS: Low-risk primiparous women
      giving birth in private hospitals have more chance of a surgical birth than a
      normal vaginal birth and this phenomenon has increased markedly in the past
      decade.

PMID- 22964121
TI  - 'Young people at high risk for psychosis: conceptual framework, research evidence
      and treatment opportunities'.

PMID- 22964122
TI  - [Not Available].

PMID- 22964123
TI  - Exogenous subclinical hyperthyroidism: effect on the cardiovascular system.
AB  - OBJECTIVE: To evaluate the effects of exogenous subclinical hyperthyroidism on
      left ventricular structure and function. MATERIAL AND METHOD: Twenty-three
      patients of both sexes, aged 27 to 70 years, with a diagnosis of exogenous
      subclinical hyperthyroidism (serum thyroid-stimulating hormone [TSH] <= 0.4mU/ml
      and normal free thyroxine [FT4]) were evaluated. The patients had been taking
      levothyroxine in suppressive doses for an average of 6.7 years (1 to 35 years).
      Twenty euthyroid individuals matched for age, sex and body mass index were
      selected as controls. A medical history was obtained and symptoms of
      thyrotoxicosis were quantified in all subjects. To evaluate left ventricular
      structure and function, as well as atrial conduction time, a two-dimensional
      echocardiogram and pulsed echo and tissue echo Doppler with electrocardiography
      monitoring were performed. The index of hemodynamic compensation of the left
      ventricular mass was calculated. RESULTS: Hyperthyroid symptom scores were
      significantly higher in patients than in controls (p=0.0001). A positive
      correlation was found between hyperthyroidism scores and FT4 (p=0.005) and
      ejection fraction (p=0.04) and a negative correlation was found with TSH levels
      (p=0.03). End-diastolic volume, stroke volume, cardiac output and stroke work
      were significantly higher in patients with SH (p=0.04, p=0.02, p=0.05 and p=0.01,
      respectively). A positive correlation was found between fractional shortening and
      FT4 level (p=0.022) and levothyroxine dose (p=0.016) and between stroke work and
      FT4 level (p=0.034). Left ventricular mass, diastolic function and atrial
      conduction time were similar in patients and controls. CONCLUSIONS: Our study
      suggests that patients with exogenous subclinical hyperthyroidism have
      hemodynamic changes resulting from adaptation to the biological effects of
      levothyroxine on the cardiovascular system. However, structural changes are not
      produced.

PMID- 22964124
TI  - Continuous glucose monitoring in insulin pump treated children.
AB  - INTRODUCTION: Insulin pump therapy aims to improve glycemic control and decrease
      the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: To evaluate interstitial
      glucose levels and the frequency, duration and symptoms of hypo- and
      hyperglycemia through the use of a continuous glucose monitoring system (GGMS) in
      children and adolescents with insulin pump-treated type 1 diabetes, and to
      determine whether this monitoring method is well tolerated by these patients.
      PATIENTS AND METHOD: Thirteen patients (4 boys) with insulin pump-treated type 1
      diabetes mellitus were monitored. Age was 10.6+/-3.5 (range, 3.2-13.6) years,
      diabetes duration was 5.0+/-3.2 years, pump therapy duration was 12.0+/-4.6
      months, insulin dose was 0.99 +/- 0.19 U/kg/day, and last hemoglobin A1c level
      was 7.1% +/- 0.8%. The Minimed CGMS was used for 72 hours. RESULTS: A 3-year-old
      preschool child did not tolerate the CGMS. Interstitial glucose concentration was
      187+/-40 mg/dl. Hypoglycemia (below 70mg/dl) accounted for 3.6% +/- 5.6% of total
      time, while hyperglycemia (above 180 mg/dl) occurred 47.3% +/- 17.4% of the time.
      No asymptomatic hypoglycemia episodes were detected. CONCLUSIONS: Insulin pump
      treated children and adolescents showed an irregular interstitial glucose level
      and did not achieve normoglycemia. In our patients, adrenergic symptoms of
      hypoglycemia were preserved and the CGMS was generally well tolerated.

PMID- 22964125
TI  - Utility of alpha subunit determination after thyrotropin-releasing hormone
      stimulation as an indicator of gonadotropinoma persistence and/or recurrence.
AB  - OBJECTIVE: Gonadotropinomas are adenomas of the gonadotropic cells of the
      anterior pituitary. These cells produce and secrete gonadotropins (follicle
      stimulating hormone and luteinizing hormone). Most of these tumors show altered
      production of gonadotropins and their subunits (the p-FSH, a and, less
      frequently, p-LH subunits). The thyrotropin-releasing hormone (TRH) stimulation
      test could differentiate these tumors from nonfunctioning tumors. Equally, this
      test could be able to distinguish between postsurgical changes and tumoral
      remnants after surgery. SUBJECTS AND METHOD: We studied 24 patients with
      pituitary macroadenoma, 14 of who had a histological diagnosis of gonadotroph
      adenoma. The TRH stimulation test was performed before and after surgery.
      RESULTS: Both before and after surgery, a positive result to the TRH test was
      obtained in 50% of gonadotropinomas. Magnetic resonance imaging (MRI) performed
      after surgery revealed that 83% of the patients with gonadotropinoma had signs of
      tumoral persistence or recurrence and/or postsurgical changes. Of these patients,
      83% (41.6% of the total) showed positive a subunit stimulation after the TRH
      test. In the group of non-gonadotropinoma macroadenomas, only 33% had a positive
      result before surgery and another 33% had a positive result after surgery. In the
      MRI performed after surgery, all showed tumoral persistence/recurrence or
      postsurgical inflammatory changes. CONCLUSIONS: This test could be useful in the
      differential diagnosis of gonadotropinomas as well as in the follow-upand
      postsurgical evaluation of these tumors.

PMID- 22964126
TI  - Risk factors of malnutrition at hospital admission.
AB  - BACKGROUND AND OBJECTIVES: Malnutrition is highly prevalent among hospitalized
      patients and is related to a greater risk of complications and mortality and more
      prolonged length of hospital stay. The aim of this study was to determine the
      prevalence of malnutrition at hospital admission and associated risk factors.
      PATIENTS AND METHOD: Nutritional screening was performed in 189 patients within
      the first 24 hours of hospitalization using Subjective Global Assessment. Sex,
      age, recent prior hospitalization, and underlying diseases were evaluated as
      possible risk factors in a univariate (chi(2)) and multivariate (logistic
      regression) model. RESULTS: The prevalence of malnutrition was 33.3%.
      Malnutrition was more frequent in males, patients with recent prior
      hospitalization, cancer or chronic diseases and was lower in patients with acute
      diseases, transplants, and surgery. There were no differences in age.
      Malnutrition was independently associated with male sex, cancer and chronic
      diseases. CONCLUSIONS: Nutritional assessment should be performed at least in
      patients with the risk factors described at hospital admission.

PMID- 22964127
TI  - Radioiodine therapy for multinodular goiter.
AB  - Treatment options for large, compressive goiters are currently limited to surgery
      and radioiodine administration. Classically, the first-line option has been
      surgery, with radioiodine therapy being reserved as an alternative treatment in
      patients with high surgical risk. We describe the case of an 81-year-old woman
      with a large, compressive multinodular goiter and hyperthyroidism, substernal
      extension and associated co-morbidity, contraindicating surgery. We review the
      efficacy of different treatment options for compressive multinodular goiter, as
      well as the potential secondary complications.

PMID- 22964128
TI  - Familial hypocalciuric hypercalcemia: review of three cases.
AB  - Familial hypocalciuric hypercalcemia, also denominated familial benign
      hypercalcemia, is an uncommon cause of hypercalcemia. It is caused by mutations
      of the calcium-sensing receptor, which are inherited in an autosomal dominant
      high-penetrance fashion. Generally, patients are asymptomatic, and heterozygote
      cases are diagnosed in childhood or adulthood, when diagnostic work-up of an
      incidentally discovered hypercalcemia ensues. This disorder is characterized by
      moderate hypercalcemia, with normal parathormone levels and low urine calcium
      excretion. It is very important to diagnose this condition, as it does not
      require surgical procedures, unlike primary hyperparathyroidism, which needs
      parathyroidectomy in 50% of cases. We present 3 cases of familial hypocalciuric
      hypercalcemia belonging to the same family, and provide an updated review on the
      topic.

PMID- 22964129
TI  - Long term treatment of a thyrotropin secreting adenoma with somatostatin
      analogues.
AB  - Thyrotropin secreting adenomas (TSH-omas) account for less than 1% of all
      pituitary adenomas and are a rare cause of hyperthyroidism. Most cases correspond
      to macroadenomas, microadenomas being exceptional. Differential diagnosis should
      be made with resistance to thyroid hormones. The first line treatment is
      transphenoidal surgery. When surgery is unsuccessful, somatostatin analogues are
      a therapeutic alternative. We report a patient with a TSH-secreting microadenoma.
      The microadenoma was resected through the transsphenoidal route. Because surgery
      was unsuccessful, medical therapy with somatostatin analogue was initiated.
      Currently, 9 years later, the patient continues to be under treatment with
      somatostatin analogue therapy, which has controlled the hyperthyroidism and
      tumoral growth. We describe successful long-term treatment of a TSH-oma with
      somatostatin analogue therapy when surgery is unsuccessful.

PMID- 22964130
TI  - Clinical descriptive measures of shoulder range of motion for a healthy, young
      and physically active cohort.
AB  - BACKGROUND: The objective of this innovative research study was to describe
      clinical shoulder complex range of motion (ROM) measures for a young, healthy,
      and physically active population. This investigation represents a cross-sectional
      experiment conducted at a military academy-based sports medicine center. Military
      cadets with no history of shoulder complex injury were assessed within two months
      of enrollment in the academy; 548 men (18.8 +/- 1.0 yr, 75.2 +/- 12.2 kg, 178.3
      +/- 7.4 cm) and 74 women (18.7 +/- 0.9 yr, 63.2 +/- 8.9 kg, 165.2 +/- 6.9 cm)
      participated. Descriptive measures included cross-body adduction (CAD), flexion
      (FLX), external rotation (ER0) with the shoulder complex in adduction and elbow
      flexed to 90 degrees , internal and external rotation (IR, ER) with the shoulder
      complex at 90 degrees  of abduction and elbow flexed to 90 degrees  as well as
      arc (ARC) of IR-ER using standardized clinical quantification techniques.
      Bilateral and sex differences were evaluated using dependent and independent t
      tests, respectively. Percentiles by arm dominance and sex were also calculated
      for all ROM measures. RESULTS: Data were normally distributed. Active and passive
      ROM measures indicated significant bilateral differences (P < 0.05) except for
      ARC. Sex differences (P < 0.05) were noted for active and passive CAD, FLX and
      ER0 for the dominant arm as well as active and passive CAD, FLX and ARC for the
      non-dominant arm. CONCLUSIONS: These original data provide descriptive measures
      for shoulder complex ROM excursions, assisting sports medicine practitioners in
      potentially identifying clinical deficiencies and functional outcomes following
      shoulder injury.

PMID- 22964131
TI  - Isolated negative T waves as independent predictors of short-term and long-term
      coronary heart disease mortality in men free of manifest heart disease in the
      Seven Countries Study.
AB  - Isolated T-wave findings are generally considered of little importance in
      clinical electrocardiogram (ECG) interpretation, although a few studies have
      associated them with excess mortality risk. We used Cox regression models to
      evaluate coronary heart disease (CHD) mortality risk for isolated inverted T
      waves in 8713 men in the Seven Countries Study with no manifest cardiac diseases
      at baseline. The study population was stratified into 3 mutually exclusive
      groups: (1) isolated inverted T waves in the absence of other codable ECG
      findings according to the Minnesota Code; (2) other ECG findings with or without
      negative T waves; and (3) no codable ECG findings, used as the reference group.
      Mortality follow-up of the entire cohort was performed at 5, 10, 20, 30, and 40
      years. The prevalence of isolated negative T waves at baseline was low, 1.6%, in
      these men from working populations. The hazard ratio (HR) for CHD mortality risk
      after 5 years in the isolated T-wave inversion group was more than 3 times
      greater than that in the reference group after adjusting for age, body mass
      index, cigarette smoking, systolic blood pressure, serum cholesterol and cohort
      (HR 3.68, 95% confidence interval [1.44-9.37]). Hazard ratio declined gradually
      with the length of follow-up but was still at 50% excess risk at 40-year follow
      up (HR 1.51, 95% confidence interval [1.12-2.05]). T waves in the isolated T-wave
      inversion group were "flat" or less negative than 1mm (-100 MUV) in the majority
      (86%) of inverted T waves. We conclude that inverted T waves with even a minor
      degree of negativity as an isolated ECG finding in men with no evidence of heart
      disease predict an excess short-term and long-term risk of CHD death.

PMID- 22964132
TI  - Semantic memory retrieval circuit: role of pre-SMA, caudate, and thalamus.
AB  - We propose that pre-supplementary motor area (pre-SMA)-thalamic interactions
      govern processes fundamental to semantic retrieval of an integrated object
      memory. At the onset of semantic retrieval, pre-SMA initiates electrical
      interactions between multiple cortical regions associated with semantic memory
      subsystems encodings as indexed by an increase in theta-band EEG power. This
      starts between 100-150 ms after stimulus presentation and is sustained throughout
      the task. We posit that this activity represents initiation of the object memory
      search, which continues in searching for an object memory. When the correct
      memory is retrieved, there is a high beta-band EEG power increase, which reflects
      communication between pre-SMA and thalamus, designates the end of the search
      process and resultant in object retrieval from multiple semantic memory
      subsystems. This high beta signal is also detected in cortical regions. This
      circuit is modulated by the caudate nuclei to facilitate correct and suppress
      incorrect target memories.

PMID- 22964133
TI  - The distinct contributions of fitness and genetic barrier to the development of
      antiviral drug resistance.
AB  - The selection of resistance to antiviral drugs depends on multiple parameters,
      including the genetic barrier that is often broadly defined as the number of
      mutations required to overcome drug selective pressure. In this review, it is
      intended to assess the roles of genetic barrier and viral fitness at various
      stages of the selection process. Several examples in the fields of HIV and HCV
      drug resistance show that the two parameters are distinct and independent. An
      analogy to the concept of kinetic versus thermodynamic control of chemical
      reactions supports a more narrow definition of the genetic barrier as the kinetic
      obstacle for the generation of genetic changes required to overcome selective
      pressure.

PMID- 22964134
TI  - From infants' to children's appreciation of belief.
AB  - Evidence is accumulating that infants are sensitive to people's false beliefs,
      whereas children pass the standard false belief test at around 4 years of age.
      Debate currently centres on the nature of early and late understanding. We defend
      the view that early sensitivity to false beliefs shown in 'online tasks' (where
      engagement with ongoing events reflects an expectation of what will happen
      without a judgement that it will happen) reflects implicit/unconscious social
      knowledge of lawful regularities. The traditional false belief task requires
      explicit consideration of the agent's subjective perspective on his reasons for
      action. This requires an intentional switch of perspectives not possible before 4
      years of age as evidenced by correlations between the false belief task and many
      different perspective-taking tasks.

PMID- 22964135
TI  - Reduced prefrontal cortex activation during the working memory task associated
      with poor social functioning in late-onset depression: multi-channel near
      infrared spectroscopy study.
AB  - A number of studies have demonstrated impairment of working memory (WM) in
      patients with major depressive disorder (MDD). However, the relationship between
      the underlying brain activity associated with impairment of WM function in MDD
      patients and their clinical characteristics is not yet clear. The objective of
      this study is to evaluate prefrontal hemodynamic response related to a WM task in
      patients with late-onset depression (LOD) and to assess the relationship between
      activation in the prefrontal cortex and clinical characteristics. Thirty-six
      patients with LOD and 35 age- and gender-matched healthy controls were recruited
      for the present study. We measured hemoglobin concentration changes in the
      prefrontal and temporal regions during a WM (2-back, letter version) task using
      52-channel near-infrared spectroscopy (NIRS). LOD patients were associated with
      reduced increase in prefrontal and temporal activation compared with healthy
      controls. Moreover, reduced activation in the prefrontal and temporal regions was
      significantly related to lower scores on the Social Adaptation Self-Evaluation
      Scale (SASS) in the patient group. More specifically, the reduced hemodynamic
      response in the frontopolar region was associated with functional impairment
      related to interpersonal relationship factor scores on the SASS. These findings
      suggest that hemodynamic response in prefrontal and temporal regions during a WM
      task may act as a biological marker of social functioning in LOD patients.

PMID- 22964136
TI  - FSH receptor in vitro modulation by testosterone and hCG in human luteinized
      granulosa cells.
AB  - OBJECTIVE: To investigate the effect of testosterone and hCG on FSH receptor
      (FSHR) protein and mRNA expression in human granulosa cells (GC) in vitro. STUDY
      DESIGN: Experimental in vitro cell culture obtained from healthy women undergoing
      IVF/ICSI due to male factor infertility. Human follicular fluid samples were
      obtained and after cumulus-oocyte complexes were identified, fluids were pipetted
      onto Ficoll gradients and centrifuged for 15 min at 400 * g at room temperature.
      Cells at the interface were removed and plated in 24-well plates for 3 days in M
      199 with 10% FBS. Cells were treated with different concentrations of
      testosterone and hCG. After purification, cells were labeled with specific
      antibodies and the protein expression of the FSHR was evaluated by flow cytometry
      in the GC population. Also, total RNA was extracted from confluent GC and the
      FSHR gene expression was evaluated by RT-PCR. RESULTS: FSHR expression was
      modulated by treating GC in vitro at different testosterone/hCG concentrations.
      When compared with untreated GC, we observed a significant effect of testosterone
      and hCG on the expression of the FSHR at the protein level. Time course
      experiments confirmed that the gene expression of the FSHR peaked at 12-24h when
      testosterone or hCG was used as a stimulus. CONCLUSIONS: Both testosterone and
      hCG are able to positively modulate FSHR expression at gene and protein level in
      human GC in vitro.

PMID- 22964137
TI  - Antiproliferative and apoptotic effects of norethisterone on endometriotic
      stromal cells in vitro.
AB  - OBJECTIVES: Low-dose estrogen-progestin (LEP) agents are often used for relieving
      endometriosis-associated chronic pelvic pain, but a direct effect of LEP on
      endometriotic lesions remains to be demonstrated. The objective of this study is
      to investigate the antiproliferative and apoptotic effects of the synthetic
      progestin norethisterone (NET) against human endometriotic stromal cells (ESCs).
      STUDY DESIGN: Ovarian endometrioma specimens were obtained at laparoscopy from 19
      patients with endometriosis, and ESCs were isolated. The antiproliferative effect
      of compounds against cultured ESCs was evaluated by measuring the inhibition of
      [(3)H]thymidine incorporation. The ability of compounds to induce apoptosis in
      the cultured cells was evaluated by the measurement of caspase 3/7 activity and
      by nuclear staining. The cytotoxicity of compounds was evaluated by measuring the
      leakage of lactate dehydrogenase (LDH) into the supernatant of the cell culture.
      RESULTS: NET and progesterone (P4) at concentrations of greater than 10nM
      significantly inhibited [(3)H]thymidine incorporation in a dose-dependent manner.
      Co-treatment with 17beta-estradiol at 0.1 ng/mL did not affect the inhibition of
      [(3)H]thymidine incorporation by NET. At concentrations greater than 100 nM, NET
      significantly increased caspase 3/7 activity and the numbers of apoptotic cells,
      whereas P4 did not. Treatment of ESCs for 24h with NET or P4 at concentrations of
      up to 1000 nM did not cause LDH leakage. CONCLUSIONS: NET inhibits the
      proliferation of ESCs and induces their apoptosis. These results suggest a
      possible direct effect of NET on endometriotic lesions in patients with
      endometriosis.

PMID- 22964138
TI  - Green tea (-)epigallocatechin-3-gallate reverses oxidative stress and reduces
      acetylcholinesterase activity in a streptozotocin-induced model of dementia.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia.
      Intracerebroventricular (ICV) infusion of streptozotocin (STZ) provides a
      relevant animal model of chronic brain dysfunction that is characterized by long
      term and progressive deficits in learning, memory, and cognitive behavior, along
      with a permanent and ongoing cerebral energy deficit. Numerous studies on green
      tea epigallocatechin gallate (EGCG) demonstrate its beneficial effects on
      cognition and memory. As such, this study evaluated, for the first time, the
      effects of sub-chronic EGCG treatment in rats that were submitted to ICV infusion
      of STZ (3mg/kg). Male Wistar rats were divided into sham, STZ, sham+EGCG and
      STZ+EGCG groups. EGCG was administered at a dose of 10mg/kg/day for 4 weeks per
      gavage. Learning and memory was evaluated using Morris' Water Maze. Oxidative
      stress markers and involvement of the nitric oxide (NO) system,
      acetylcholinesterase activity (AChE) and glucose uptake were evaluated as well as
      glial parameters including S100B content and secretion and GFAP content. Our
      results show that EGCG was not able to modify glucose uptake and glutathione
      content, although cognitive deficit, S100B content and secretion, AChE activity,
      glutathione peroxidase activity, NO metabolites, and reactive oxygen species
      content were completely reversed by EGCG administration, confirming the
      neuroprotective potential of this compound. These findings contribute to the
      understanding of diseases accompanied by cognitive deficits and the STZ-model of
      dementia.

PMID- 22964139
TI  - Electrophysiological correlates of biological motion permanence in humans.
AB  - Spatiotemporal discontinuity of visual input is a common occurrence in daily
      life. For example, when a walking person disappears temporarily behind a wall,
      observers have a clear sense of his physical presence despite the absence of any
      visual information (movement permanence). To investigate the neural substrates of
      biological motion permanence, we recorded scalp EEG activity of sixteen subjects
      while they passively observed either biological or scrambled motion disappearing
      behind an occluder and reappearing. The moment of the occluder's appearance was
      either fixed or randomized. The statistical comparison between the biological and
      scrambled motion ERP waveforms revealed a modulation of activity in centro
      parietal and right occipito-temporal regions during the occlusion phase when the
      biological motion disappearance was time-locked, possibly reflecting the recall
      of sensorimotor representations. These representations might allow the prediction
      of moving organisms in occlusion conditions. When the appearance of the occluder
      was unpredictable there was no difference between biological and scrambled motion
      either before or during occlusion, indicating that temporal prediction is
      relevant to the processing of biological motion permanence.

PMID- 22964140
TI  - Fucanomics and galactanomics: current status in drug discovery, mechanisms of
      action and role of the well-defined structures.
AB  - BACKGROUND: With the recent advent of glycomics, many medically relevant glycans
      have been discovered. Sulfated fucans (SFs) and sulfated galactans (SGs) are one
      of these classes of glycans with increasing interest to both glycomics and
      medicine. Besides having very unique structures, some of these molecules exhibit
      a broad range of pharmacological actions. In certain cases, high levels of
      effectiveness may be reached when the proper structural requirements are found.
      SCOPE OF REVIEW: Here, we cover the fundamental biochemical mechanisms of some of
      these medicinal properties. We particularly focus on the beneficial activities of
      SFs and SGs in inflammation, hemostasis, vascular biology, and cancer. MAJOR
      CONCLUSIONS: In these clinical systems, intermolecular complexes directly driven
      by electrostatic interactions of SFs and SGs with P- and L-selectins, chemokines,
      antithrombin, heparin cofactor II, thrombin, factor Xa, bFGF, and VEGF, overall
      govern the resultant therapeutic effects. In spite of that, the structural
      features of SFs and SGs have shown to be essential determinants for formation and
      stability of those molecular complexes, which consequently account to the
      differential levels of the biomedical responses. GENERAL SIGNIFICANCE: Accurate
      structure-function relationships have mostly been achieved when SFs and SGs of
      well-defined structures are used for study. Therefore, these types of glycans
      have become of great usefulness to identify the chemical requirements needed to
      achieve satisfactory clinical responses.

PMID- 22964141
TI  - Risk of breast implant bacterial contamination from endogenous breast flora,
      prevention with nipple shields, and implications for biofilm formation.
AB  - BACKGROUND: Capsular contracture (CC) is a common complication of breast
      augmentation that is thought to arise from bacterial contamination and subsequent
      biofilm formation on the implant. Endogenous breast flora expressed through the
      nipple may contaminate the sterile field during breast augmentation, acting as a
      possible source for initiation of biofilm formation. OBJECTIVES: The authors
      investigate the incidence of nipple bacterial contamination with endogenous
      breast flora after standard chest wall sterilization during breast augmentation.
      METHODS: Bacterial contamination of nipples and nipple shields was assessed in a
      series of 32 consecutive patients presenting for breast augmentation (63 breasts:
      31 bilateral procedures and 1 unilateral procedure). After standard sterilization
      of the chest wall, occlusive nipple shields were applied and breast augmentation
      was performed. At the conclusion of breast augmentation, the nipple shields were
      removed and, using the same swab, both the nipple/areolar area and occlusive
      dressings were cultured. RESULTS: Data from 63 cultured nipples and nipple
      shields revealed that 22 nipples/nipple shields (34.9%) were positive for
      bacterial contamination. Three patients, all of whom had negative cultures,
      developed CC after augmentation. CONCLUSIONS: The exposed nipple is a potential
      source of implant contamination during breast augmentation. An improved
      understanding of biofilms and related risk factors for CC can provide surgeons
      with insights for addressing this common complication. Meticulous hemostasis, use
      of nipple shields, and submuscular device placement may contribute to a lower
      incidence of CC.

PMID- 22964142
TI  - Characteristics associated with anti-osteoporosis medication use: data from the
      Global Longitudinal Study of Osteoporosis in Women (GLOW) USA cohort.
AB  - INTRODUCTION: Many women at risk of fracture do not receive anti-osteoporosis
      medication (AOM), while others may be receiving unnecessary treatment. PURPOSE:
      To examine the characteristics associated with AOM use among women at low and
      high risks of fracture. METHODS: The Global Longitudinal Study of Osteoporosis in
      Women (GLOW) is a prospective cohort study in which data were collected, via self
      administered questionnaires, from 60,393 non-institutionalized women aged >= 55
      years in 10 countries between October 1, 2006 and April 30, 2008. This is a cross
      sectional analysis of baseline USA data, in which women were classified as having
      low fracture risk (<65 years; no FRAX risk factors) or high fracture risk (>=65
      years; prior fracture or >= 2 other FRAX risk factors). RESULTS: Of 27,957 women,
      3013 were at low risk of fracture and 3699 were at high risk. Only 35.7% of high
      risk women reported AOM treatment, rising to 39.5% for those with self-reported
      osteopenia and 65.4% for those with self-reported osteoporosis. Conversely, 13.4%
      of low-risk women reported AOM, rising to 28.7% for osteopenia and 62.4% for
      osteoporosis. Characteristics associated with significantly higher AOM treatment
      rates among low- and high-risk women were: osteoporosis (odds ratios 75.3 and
      18.1, respectively), osteopenia (17.9 and 6.3), concern about osteoporosis (2.0
      and 1.8), higher perceived risk of fracture (2.3 and 1.6), and higher vitality
      score (1.7 and 1.6). CONCLUSION: Use of AOM is frequently inconsistent with
      published guidelines in both high- and low-risk women. Characteristics other than
      FRAX fracture risk appear to influence this use, particularly the presence of
      self-reported osteoporosis.

PMID- 22964143
TI  - Adverse pregnancy outcomes in women with diabetes.
AB  - Pregnancy affects both the maternal and fetal metabolism and even in nondiabetic
      women exerts a diabetogenic effect. Among pregnant women, 2 to 17.8% develop
      gestational diabetes. Pregnancy can also occur in women with preexisting
      diabetes, that can predispose the fetus to many alterations in organogenesis,
      growth restriction and the mother to some diabetes-related complications like
      retinopathy and nephropathy or accelerate the course of these complications if
      they are already present. Women with gestational diabetes generally start their
      treatment with diet and lifestyle modification; when these changes fail in
      keeping an optimal glycemic control, then insulin therapy must be considered.
      Women with type 2 diabetes in use of oral hypoglycemic agents are advised to
      change to insulin therapy. Those with preexisting type 1 diabetes must start an
      intensive glycemic control, preferably before conception. All these procedures
      are performed aiming to keep glycemic levels normal or near-normal as possible to
      avoid the occurrence of adverse perinatal outcomes to the mother and to the
      fetus. The aim of this review is to reinforce the need to improve the knowledge
      on reproductive health of women with diabetes during gestation and to understand
      what are the reasons for them failing to attend for prepregnancy care programs,
      and to understand the underlying mechanisms of adverse fetal and maternal
      outcomes, which in turn may lead to strategies for its prevention.

PMID- 22964144
TI  - [Efficacy of radiofrequency ablation to treat advanced hepatocellular carcinoma].
AB  - OBJECTIVE: To retrospectively investigate the feasibility of radiofrequency
      ablation (RFA) in treating advanced hepatocellular carcinoma (HCC) using standard
      ultrasound-guided percutaneous RFA. METHODS: A total of 655 patients with
      unresectable advanced HCC underwent ultrasound-guided percutaneous RFA therapy at
      our institution between July 2000 to September 2001. Ninety-two of those
      patients, representing 136 tumors, were selected for analysis based on the
      following criteria: presence of UICC/AJCC-TNM (6th edition) stage III and IV
      advanced HCC, (III: n=82 patients, with 126 tumors; IV: n=10 patients, with 10
      tumors); extensive portal vein or inferior vena cava tumor thrombus; extrahepatic
      metastasis after surgical resection; and complete follow-up data. Follow-up
      consisted of enhanced computed tomography (CT) performed at one month post-RFA
      treatment, then every three months. Contrast-enhanced ultrasound (CEUS) was
      performed in 51 (55.4%) patients before RFA. The standard treatment using optimal
      strategies were applied in (72.8%) 67 patients. The established strategies
      included: (1) select RFA indications based on CEUS results; (2) design radical
      protocols based on invasive range showed by CEUS; (3) multiple overlapping
      ablations based on mathematical protocols; (4) two or three bipolar RFA
      electrodes with three-dimensional localization; (5) color ultrasound-guided
      percutaneous ablation of tumor feeding artery (PAA)/transcatheter arterial
      chemoembolization (TACE) + RFA for HCC with rich supply. The other 25 patients
      (27.2 %) were treated with conventional RFA protocols. The ablation procedure was
      considered a success if no abnormal enhancement or wash-out was detected in the
      treated area on the CT scan at one month. All patients had received liver
      protection treatments following RFA. Chi-squared test or Fisher's exact test were
      used to compare the early complete tumor necrosis rates and the local recurrence
      rates. Survival was estimated by Kaplan-Meier analysis and log-rank test. P less
      than 0.05 was considered statistically significant. RESULTS: The RFA-treated
      tumors ranged in size from 1.5 to 7.0 cm (average: 4.5 cm). Fifty-nine patients
      had solitary tumor, and the remaining 33 had multiple tumors (2 to 4 tumors).
      Patients were classified by Child-Pugh score as A (n=58), B (n=32) and C (n=2).
      Early complete tumor necrosis rate after initial RFA was 90.4% (123/136 tumors).
      Serious complications developed in two patients (2.2%). No treatment-related
      death occurred. Follow-up ranged from 3-134 months. Local recurrence rate was
      16.9% (23/136 tumors). The 1-, 3- and 5-year overall survival rates were 83.3%,
      48.3% and 21.9%, respectively, and the median survival time was 35 months.
      Stratification analysis indicated the early complete tumor necrosis rate was
      higher in groups of patients with Child-Pugh A score (98.3%) , CEUS
      administration (98.0%), and standard treatment (97.0%). The local recurrence rate
      was lower in groups of patients with tumors less than or equal to 3.0 cm (5.9%),
      CEUS administration (11.8%), and standard treatment (16.4%). The 5-year survival
      was significantly higher in patients with Child-Pugh A, tumors less than or equal
      to 3.0 cm, CEUS administration, and standard treatment (all, P less than 0.05).
      CONCLUSION: RFA treatment of patients with advanced HCC, tumors less than 7.0 cm,
      and without thrombosis in the main vessels was efficacious. The RFA treatment
      strategy and subsequent liver protection therapy in RFA may improve survival.

PMID- 22964145
TI  - [The new technology of enhanced radiofrequency ablation is safe and effective for
      treating giant hepatic hemangioma].
AB  - OBJECTIVE: To determine the safety and efficacy of the enhanced radiofrequency
      ablation (RFA) new technology for treatment of giant hepatic hemangiomas.
      METHODS: From August 2010 to September 2011, 30 patients with giant hepatic
      hemangiomas (average diameter: 7.7+/-1.9 cm, range: 5.0 to 12.8 cm) were treated
      with enhanced RFA. The original lesion diameter, enhanced radiofrequency
      duration, and cases of RFA-induced burning were recorded. Cases requiring a
      second RFA treatment were also recorded. Correlation analysis was carried out to
      determine the association of enhanced RFA with adverse events and change in
      lesion diameter. RESULTS: The rate of completely destroyed lesions by enhanced
      RFA was 70.96%, and the total rate of reduced lesions was 87.1%. No severe
      adverse events occurred. The duration of enhanced radiofrequency correlated
      positively with the original lesion diameter (r=0.687, P less than 0.01). The
      enhanced RFA treatment significantly reduced the average lesion diameter (follow
      up: 6.2+/-1.8 cm; t=6.417, P less than 0.01). CONCLUSION: The new minimally
      invasive technology of enhanced radiofrequency ablation is effective and safe for
      treating giant hepatic hemangiomas and produces an obvious, short-term curative
      effect.

PMID- 22964146
TI  - [Ultrasound-guided assistant infusion technique for percutaneous radiofrequency
      ablation of liver cancer].
AB  - OBJECTIVE: To assess the value of an infusion-based separation technique to
      assist in ultrasound (US)-guided percutaneous radiofrequency ablation (RFA) of
      liver cancers abutting the liver edge. METHODS: Twenty-four cases of malignant
      liver tumors abutting the hepatic edge were treated with US-guided puncture
      accompanied by the assistant infusion technique. The US-guided puncture was made
      with a 22-G needle through the hepatic tissue and into the abdominal cavity near
      the target tumor. Infusion of a saline solution was used to separate the liver
      from any surrounding structures so that percutaneous RFA could be safely
      performed. Complications, including gastrointestinal injury, hemorrhage and
      death, were recorded. Technical efficacy and safety were evaluated. RESULTS:
      Among the 24 patients, the target tumors were adjacent to the right kidney (n=6),
      colon (n=6), stomach (n=5), pericardium (n=4), and gall bladder (n=3). Twenty
      three patients received a successful radical percutaneous RFA with assistant
      infusion. The assistant infusion volumes ranged from 80-390 ml and created spaces
      ranging from 0.8-2.5 cm between the liver and surrounding structures. Five of the
      cases with tumors adjacent to the stomach or colon received the largest volume
      infusions. The infusion failed to create a separation space in only one case, due
      to the presence of an adhesion; as a result, this patient was treated with
      palliative RFA. The mean hospital stay for all 24 patients was four days after
      surgery. No severe complications or deaths occurred. At 1-month follow-up,
      computed tomography images showed that 22 cases had complete ablation, yielding a
      technical success rate of 95.7% (22/23). No needle track implantation was
      observed. CONCLUSION: Assistant infusion for percutaneous radiofrequency ablation
      creates a protective space between the liver and surrounding structures in
      patients with liver tumors abutting the liver edge. This safe and effective
      assistant technique broadens the range of patients available for percutaneous RFA
      treatment.

PMID- 22964147
TI  - [Expression of epidermal fatty acid-binding protein in cross-species
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the utility of the cross-species screening strategy for
      investigating key molecule(s) involved in onset and progression of hepatocellular
      carcinoma (HCC). METHODS: HCC-related molecule data from our previous studies and
      in the literature were collected to establish a cross-species dataset. Tissue
      samples of HCC, non-HCC surrounding liver (para-HCC), and normal liver that were
      collected from humans, tree shrews and rats. The genes reported to have the most
      differential expression in HCC were verified by analyzing the mRNA and protein
      levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blotting, respectively. RESULTS: The cross-species dataset of HCC-related
      molecules included four genes: epidermal fatty acid-binding protein (E-FABP),
      liver (L)-FABP, tyrosine a-ketoglutarate transaminase (TKT), and cytokeratin
      (CK8). In humans, E-FABP mRNA expression was significantly higher (P less than
      0.05) in HCC (0.87+/-0.14 vs. para-HCC: 0.64+/-0.12 and normal liver: 0.67+/
      0.07; F=20.910). Similar results were obtained in tree shrew (HCC: 0.87 +/- 0.25
      vs. para-HCC: 0.73 +/- 0.19 and normal liver: 0.68+/-0.19; F=3.807) and rat (HCC:
      0.97+/-0.22 vs. para-HCC: 0.78+/-0.16 and normal liver: 0.80 +/- 0.13; F=4.482).
      The Western blotting analyses revealed a similar statistically significant trend.
      CONCLUSION: The cross-species screening strategy for tumor genes may represent a
      feasible and convenient process of identifying key molecule(s) for human HCC. E
      FABP may be a particularly crucial molecule for hepatocarcinogenesis.

PMID- 22964148
TI  - [Clusterin is a potential serum marker of hepatic carcinoma].
AB  - OBJECTIVE: To determine the differentially expressed serum proteins in patients
      with hepatoma carcinoma and identify a putative diagnostic marker. METHOD: The
      isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and
      LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in
      hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real
      time reverse transcription-polymerase chain reaction was used to verify the
      differentially expressed proteins by analyzing the corresponding mRNA expression
      levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30
      pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples.
      Western blot analysis was used to verify the protein expression in hepatic
      carcinoma cells. RESULT: Fifty-one proteins were significantly differentially
      expressed between the hepatic carcinoma group and healthy controls. The iTRAQ
      protein profile showed that the serum level of clusterin was significantly lower
      in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in
      hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in
      hepatoma tissues than that in adjacent normal tissues. The clusterin protein
      levels were significantly lower in hepatic carcinoma cells (8.06 vs normal
      hepatocytes: 27.81; P less than 0.01). CONCLUSION: The serum expression of
      clusterin is significantly decreased in both serum and tissues of hepatic
      carcinoma patients. The relationship between hepatic carcinoma and clusterin
      should be evaluated in future studies.

PMID- 22964149
TI  - [Clinical characteristics and effect of secondary individualized therapy in
      chronic hepatitis B patients infected with the rtA181 mutation hepatitis B
      virus].
AB  - OBJECTIVE: To investigate chronic hepatitis B (CHB) patients infected with the
      antiviral-resistant rtA181 mutation hepatitis B virus (HBV) who have been
      unresponsive to general therapy to determine the effects of individualized
      therapy. METHODS: Fifty-four patients with confirmed rtA181 mutation and who
      experienced virological breakthrough during nucleus(t)ide analogue (NUC)
      treatment were enrolled in this prospective cohort study. Their serum levels of
      HBV DNA, hepatitis B surface antigen (HBsAg), and alanine transaminase (ALT) were
      tested. Each patient was genotyped by pyrosequencing for 10 mutation sites in the
      HBV P gene that have been previously correlated to NUC efficacy. Each patient's
      antiviral therapy and response history was analyzed in regard to their particular
      mutation pattern. The serological index was determined for carriers of the
      rtA181T/V mutation. The secondary individualized treatment included
      adding/switching to entecavir (ETV; group A) or adding telbivudine (LdT; group B)
      upon confirmation of drug resistance. Effect of individualized treatment was
      analyzed by T test and Mann-Whitney U test for continuous variables with normal
      or skewed distributions, respectively. Categorical variables were analyzed by the
      Chi-squared ( x2 ) or Fisher's exact tests. RESULTS: The rtA181T mutation was
      found in 64.8% (35/54) of patients with rtA181 mutation HBV. The most frequent
      previously administered medications were adefovir dipivoxil (ADV) and lamivudine
      (LAM). Multi-site rtA181 mutations occurred more frequently in the patients with
      multi-NUCs history (57.6%) than in those with single NUCs history (28.6%)
      (x2=4.342, P less than 0.05). Serum HBV DNA level at virological breakthrough was
      lower than that at baseline of the first antiviral treatment (5.66+/-1.01 vs.
      6.75+/-0.81 log10 copies/ml; t=-4.210, P less than 0.01). The serum HBsAg level
      was higher in carriers of the rtA181T mutation than in carriers of the rtA181V
      mutation (3.80+/-0.45 vs. 3.46+/-0.60 log10 IU/ml; t=2.109, P less than 0.05). In
      patients with serum HBV DNA more than or equal to 6 log10 copies/ml at viral
      breakthrough, 100% (8/8) of patients in the secondary treatment group A and 75%
      (3/4) patients in the secondary treatment group B exhibited virological response
      at week 24 after intervention. Undetectable HBV DNA was achieved in three
      patients of group A and one patient of group B. In patients with serum HBV DNA
      less than 6 log10 copies/ml at viral breakthrough, 100% (14/14) of patients in
      group A and 71.4% (5/7) of patients in group B exhibited biological response at
      week 24 after intervention. The serum HBV DNA level decreased to undetectable
      levels in 12 patients of group A and four patients of group B. CONCLUSION: The
      rtA181 mutation pattern correlates with previous antiviral therapy response. In
      addition, multi-site rtA181 mutations occur more frequently in patients with a
      history of multi-NUCs therapy. Adding or switching rtA181 carriers to ETV
      produces a more robust virological suppression than adding LdT.

PMID- 22964150
TI  - [Impact of liver steatosis on antiviral effects of pegylated interferon-alpha in
      patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the impact of hepatic steatosis on virologic response
      in chronic hepatitis B (CHB) patients treated with pegylated interferon-alpha
      (PEG-IFNa). METHODS: Ninety-six naive patients positive for hepatitis B e antigen
      (HBeAg) and with biopsy-proven CHB were administered PEG-IFNa-2a or PEG-IFNa-2b
      for 48 weeks. Virologic response (HBeAg clearance and hepatitis B virus (HBV) DNA
      less than 5 log10 copies/ml) and biochemical response (alanine transaminase (ALT)
      normalization) were compared between patients with (n=34) and without (n=62)
      steatosis. RESULTS: The HBV DNA titer in the steatosis group was significantly
      lower than that of the non-steatosis group (6.961.27 vs. 7.541.28 log10
      copies/ml; t=2.161, P=0.033). After 48 weeks of PEG-IFNa treatments, there was no
      significant difference in HBeAg seroconversion or the percentage of undetectable
      HBV DNA (less than 3 log10 copies/ml) between steatosis and non-steatosis
      patients. However, the steatosis patients presented with a significantly lower
      complete response rate (virologic response plus biochemical response) compared to
      non-steatosis patients (26.5% vs. 48.4%; x2 =4.373, P=0.037). Of the 45 CHB
      patients with undetectable HBV DNA after 48 weeks of treatment, seven did not
      achieve ALT normalization. The rate of patients with non-biochemical response was
      significantly higher in the steatosis group than in the non-steatosis group
      (33.3% vs. 6.67%; P=0.032). CONCLUSION: Hepatic steatosis does not affect the
      virologic response, but does affect the biochemical response in CHB patients
      treated with PEG-IFNa for 48 weeks.

PMID- 22964151
TI  - [Effect of TGF-b1 siRNA-mediated silencing on Smad proteins in hepatic fibrosis
      rats].
AB  - OBJECTIVE: To investigate the changes in Smad 2, 3, 4 and 7 of the transforming
      growth factor-beta 1 (TGF-b1)/Smad signaling pathways in carbon tetrachloride
      (CCL4)-induced hepatic fibrosis rats treated with TGF-b1 small interfering
      (si)RNA. METHODS: Rats were randomly divided among five groups: non-fibrotic
      (normal); fibrosis-induced (model); fibrotic treated with 0.125 mg/kg TGF-b1
      siRNA; fibrotic treated with 0.250 mg/kg TGF-b1 siRNA; and fibrotic treated with
      negative control TGF-b1 siRNA. The expression of Smad 2, 3, 4 and 7 was detected
      by real-time polymerase chain reaction (for mRNA), immunohistochemistry and
      Western blotting (for protein). RESULTS: The mRNA and protein levels of Smad 2, 3
      and 4 were significantly lower in the the fibrotic rats treated with either 0.250
      mg/kg or 0.125 mg/kg TGF-b1 siRNA than in the fibrotic model or the negative
      control TGF-b1 siRNA rats (P less than 0.01). Moreover, the mRNA and protein
      expression levels of Smad 2, 3 and 4 were significantly lower in the 0.250 mg/kg
      TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). Comparing
      the 0.250 mg/kg and 0.125 mg/kg TGF-b1 siRNA groups to the model group and the
      TGF-b1 siRNA negative control group showed significantly increased levels of mRNA
      and protein expression of Smad 7 (P less than 0.01). In addition, the expression
      levels of Smad 7 were significantly higher in the 0.250 mg/kg TGF-b1 siRNA group
      than in the 0.125 mg/kg group (P less than 0.05). CONCLUSION: siRNA-mediated
      silencing of TGF-b1 in rats led to significantly reduced expression of Smad 2, 3
      and 4, but significantly increased expression of Smad 7. TGF-b1 regulation of
      Smad signaling molecules may contribute to hepatic fibrosis in rats and represent
      a target of future therapeutic intervention.

PMID- 22964152
TI  - [Impact of artesunate on the expression and secretion of transforming growth
      factor-b1 of primary rat hepatic stellate cells].
AB  - OBJECTIVE: To investigate the impact of the Artemisia annua plant-derived drug,
      artesunate, on proliferation of primary rat hepatic stellate cells (HSCs), and to
      analyze the underlying molecular mechanisms of its anti-fibrogenic effects
      involving the inhibition of transforming growth factor-beta 1 (TGF-b1) expression
      and secretion in liver. METHOD: Isolated, cultured, and activated primary rat
      HSCs were divided into sixteen groups, including one untreated control group and
      fifteen artesunate-treated experimental groups with 125, 150, 175, 200 or 225
      mumol/L for 24, 48 or 72 hours. The rate of cellular proliferation was measured
      using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)
      assay. TGF-b1 mRNA expression was evaluated by reverse transcription-polymerase
      chain reaction and protein expression was evaluated by Western blotting. Enzyme
      linked immunosorbent assay was used to evaluate secreted levels of TGF-b1
      protein. RESULTS: Artesunate significantly inhibited proliferation of cultured
      HSCs in a dose- and time-dependent manner (all, P less than 0.01). After 24 hours
      of exposure, the inhibition ratios of the various artesunate concentrations were:
      6.06%+/-1.44% (125 mumol/L), 21.47%+/-5.57% (150 mumol/L), 42.00%+/-7.36% (175
      mumol/L), 67.12%+/-4.55% (200 mumol/L), and 79.83%+/-3.67% (225 mumol/L).
      Artesunate significantly inhibited the TGF-b1 mRNA expression in HSCs, and the
      higher the drug concentration, the higher the degree of inhibition (all, P less
      than 0.01). In addition, artesunate significantly inhibited the expression of
      intracellular and secreted TGF-b1 protein (all, P less than 0.01). In response to
      artesunate (mumol/L concentrations), the TGF-b1 levels were (164.24+/-6.88) pg/ml
      (0MUmol/L), (102.68+/-4.45) pg/ml (150MUmol/L), (86.54+/-5.56) pg/ml
      (175MUmol/L), and (56.55+/-5.66) pg/ml (200MUmol/L). CONCLUSION: Artesunate
      exerts anti-fibrogenic effects on HSCs in vitro, possibly by reducing the
      expression, translation and secretion of TGF-b1.

PMID- 22964153
TI  - [Clinical and pathological analysis of 566 patients with cryptogenic liver
      diseases].
AB  - OBJECTIVE: To investigate the etiology, pathology, and clinical characteristics
      of cryptogenic liver diseases in order to develop a pathogenic profile for
      clinical diagnosis and therapeutic design. METHODS: The data of the 566 patients
      diagnosed with abnormal liver function and who had undergone liver biopsy at our
      institute between January 2006 to March 2010 were retrospectively analyzed. The
      Chi-squared (x2) test was used to assess disease correlation with sex and the
      rank sum test was used to assess disease correlation with continuous data since
      all data had asymmetric distribution. RESULTS: Among the 566 patients, abnormal
      liver function was attributed to alcoholic liver disease (n=175; 30.92%), drug
      induced or environmentally-induced liver disease (n=101; 17.84%), hereditary and
      metabolic disease (n=93; 16.43%), infectious hepatitis disease (n=84; 14.84%),
      fatty liver disease (n=53; 9.36%), and autoimmune liver disease (n=30; 53.00%).
      Thirty patients had unknown etiology, despite liver biopsy analysis. Among these
      disease subgroups, there were distinct correlations with sex, age, and levels of
      alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The autoimmune
      liver disease group was correlated with sex (q=9.14, 7.435, 5.071, 9.529, and
      12.5, respectively; P less than or equal to 0.01). The alcoholic liver disease
      group and autoimmune liver disease group were correlated with age (vs. genetic
      metabolic disease group: q=17.254 and 10.302; infectious hepatitis group:
      q=17.523 and 10.697); drug/environmentally-induced liver damage group: q=9.170
      and 5.266); fatty liver group: q=7.118 and 4.661) (P less than or equal to 0.01).
      In addition, the alcoholic and autoimmune liver disease groups were correlated
      with GGT levels (vs. genetic metabolic disease group: q=8.003; infectious
      hepatitis group: q=4.793; drug/environmentally-induced liver damage group:
      q=4.404) (P less than or equal to 0.01). CONCLUSION: Liver pathology is important
      for the diagnosis of cryptogenic liver diseases. Patient age, sex, and
      biochemistry index may facilitate diagnosis and treatment in the absence of
      pathology.

PMID- 22964154
TI  - [Simvastatin inhibits activation of hepatic stellate cells and promotes
      activation of adenosine monophosphate-activated protein kinase].
AB  - OBJECTIVE: To investigate the underlying molecular mechanism of the cholesterol
      blocking drug, simvastatin, in treating nonalcoholic fatty liver fibrosis.
      METHOD: A rat model of nonalcoholic fatty liver fibrosis was established by
      feeding Wistar rats a fat-rich diet. After treatment with simvastatin (4
      mg/kg/day), liver histological specimens were stained with hematoxylin-eosin and
      Masson's trichrome for microscopic analysis. Expression of adenosine
      monophosphate-activated protein kinase-alpha (AMPKa) was evaluated by reverse
      transcription-polymerase chain reaction (RT-PCR; for mRNA) and Western blotting
      (protein). The levels of serum total cholesterol (TC), triglycerides (TG),
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor
      necrosis factor-alpha (TNFa) were measured by standard biochemical assays. The
      human hepatic stellate cell line, LX-2 (quiescent or activated), was treated with
      transforming growth factor-beta 1 (TGF-b1) alone, simvastatin alone, or TGF-b1 +
      simvastatin. RT-PCR and Western blotting were used to determine changes in AMPKa
      mRNA and protein expression, respectively. RESULTS: In the rat model of
      nonalcoholic fatty liver fibrosis, the extent of pathological changes in hepatic
      tissues correlated with severity of disease progression. The levels of serum TC,
      TG, ALT, AST and TNFa were increased significantly in model rats (vs. healthy
      controls; all, P less than 0.01). AMPKa mRNA expression and activity was
      significantly decreased in model rats (vs. healthy controls; P less than 0.01 and
      P less than 0.05, respectively). Simvastatin, treatment significantly improved
      all of these parameters in model rats (vs. untreated model rats; all, P less than
      0.05). In vitro simvastatin treatment of human HSCs significantly increased AMPKa
      activity (quiescent LX-2: 0.93+/-0.10 vs. 0.72+/-0.09, activated LX-2: 0.72+/
      0.10 vs. 0.54+/-0.10, q=7.00, 6.00; all, P less than 0.01), decreased a-smooth
      muscle actin expression (mRNA: 0.30+/-0.02 vs. 0.36+/-0.02, protein: 0.30+/-0.03
      vs. 0.38+/-0.02, q=11.245, 11.216; all, P less than 0.01), and decreased collagen
      I expression (mRNA: 0.30+/-0.03 vs. 0.37+/-0.03, protein: 0.25+/-0.03 vs. 0.33+/
      0.03, q=8.791, 11.163; all, P less than 0.01). CONCLUSION: Simvastatin may
      improve nonalcoholic fatty liver fibrosis by inducing AMPK phosphorylation.

PMID- 22964156
TI  - Recent advances in benefits and hazards of engineered nanoparticles.
AB  - Over recent decades, engineered nanoparticles are increasingly produced as the
      result of the rapid development in nanotechnology. They are currently used in a
      wide range of industrial and public sectors including healthcare, agriculture,
      transport, energy, materials, and information and communication technologies. As
      the result, an increasing concern has been raised over the potential impacts of
      engineered nanoparticles to human health. In the light of this, it is the purpose
      of the present review to discuss: (1) novel properties of engineered
      nanoparticles particularly in biomedical sciences, (2) most recently reported
      adverse effects of manufactured nanoparticles on human health and (3) different
      aspects of toxicological risk assessment of these nanoparticles.

PMID- 22964155
TI  - Genome-wide study of DNA methylation alterations in response to diazinon exposure
      in vitro.
AB  - Pesticide exposure has repeatedly been associated with cancers. However,
      molecular mechanisms are largely undetermined. In this study, we examined whether
      exposure to diazinon, a common organophosphate that has been associated with
      cancers, could induce DNA methylation alterations. We conducted genome-wide DNA
      methylation analyses on DNA samples obtained from human hematopoietic K562 cell
      exposed to diazinon and ethanol using the Illumina Infinium HumanMethylation27
      BeadChip. Bayesian-adjusted t-tests were used to identify differentially
      methylated gene promoter CpG sites. We identified 1069 CpG sites in 984 genes
      with significant methylation changes in diazinon-treated cells. Gene ontology
      analysis demonstrated that some genes are tumor suppressor genes, such as
      TP53INP1 (3.0-fold, q-value <0.001) and PTEN (2.6-fold, q-value <0.001), some
      genes are in cancer-related pathways, such as HDAC3 (2.2-fold, q-value=0.002),
      and some remain functionally unknown. Our results provided direct experimental
      evidence that diazinon may modify gene promoter DNA methylation levels, which may
      play a pathological role in cancer development.

PMID- 22964157
TI  - Opposite effects of two trichothecene mycotoxins, deoxynivalenol and nivalenol,
      on the levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in
      HL60 cells.
AB  - To elucidate the mechanisms underlying the toxicities of the trichothecene
      mycotoxins deoxynivalenol and nivalenol, their effects on the secretion of anti
      hematopoietic chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha) and
      MIP-1beta in human promyelocytic leukemia cell line HL60 were investigated.
      Exposure to deoxynivalenol for 24h significantly induced the secretion of
      chemokines. The induction of these chemokines may account for the leukopenia
      after exposure to trichothecene mycotoxins. Treatment with nivalenol decreased
      the secretion of these chemokines. Our finding that deoxynivalenol induces the
      secretion of these chemokines, whereas nivalenol has the opposite effect, clearly
      indicates that the toxicity mechanisms of deoxynivalenol and nivalenol differ.

PMID- 22964158
TI  - Promoting health and reducing health inequities in Europe.

PMID- 22964159
TI  - WHO European review of social determinants of health and the health divide.
AB  - The European region has seen remarkable heath gains in those populations that
      have experienced progressive improvements in the conditions in which people are
      born, grow, live, and work. However, inequities, both between and within
      countries, persist. The review reported here, of inequities in health between and
      within countries across the 53 Member States of the WHO European region, was
      commissioned to support the development of the new health policy framework for
      Europe: Health 2020. Much more is understood now about the extent, and social
      causes, of these inequities, particularly since the publication in 2008 of the
      report of the Commission on Social Determinants of Health. The European review
      builds on the global evidence and recommends policies to ensure that progress can
      be made in reducing health inequities and the health divide across all countries,
      including those with low incomes. Action is needed--on the social determinants of
      health, across the life course, and in wider social and economic spheres--to
      achieve greater health equity and protect future generations.

PMID- 22964161
TI  - Predicting the impact of hospital health information technology adoption on
      patient satisfaction.
AB  - OBJECTIVES: To develop and explore the predictability of patient perceptions of
      satisfaction through the hospital adoption of health information technology
      (HIT), leading to a better understanding of the benefits of increased HIT
      investment. DATA AND METHODS: The solution proposed is based on comparing the
      predictive capability of artificial neural networks (ANNs) with the adaptive
      neuro-fuzzy inference system (ANFIS). The latter integrates artificial neural
      networks and fuzzy logic and can handle certain complex problems that include
      fuzziness in human perception, and non-normal and non-linear data. Secondary data
      from two surveys were combined to develop the model. Hospital HIT adoption
      capability and use indicators in the Canadian province of Ontario were used as
      inputs, while patient satisfaction indicators of healthcare services in acute
      hospitals were used as outputs. RESULTS: Eight different types of models were
      trained and tested for each of four patient satisfaction dimensions. The accuracy
      of each predictive model was evaluated through statistical performance measures,
      including root mean square error (RMSE), and adjusted coefficient of
      determination R(2)(Adjusted). For all four patient satisfaction indicators, the
      performance of ANFIS was found to be more effective (R(Adjusted)(2)=0.99) when
      compared with the results of ANN modeling in predicting the impact of HIT
      adoption on patient satisfaction (R(Adjusted)(2)=0.86-0.88). CONCLUSIONS: The
      impact of HIT adoption on patient satisfaction was obtained for different HIT
      adoption scenarios using ANFIS simulations. The results through simulation
      scenarios revealed that full implementation of HIT in hospitals can lead to
      significant improvement in patient satisfaction. We conclude that the proposed
      ANFIS modeling technique can be used as a decision support mechanism to assist
      government and policy makers in predicting patient satisfaction resulting from
      the implementation of HIT in hospitals.

PMID- 22964160
TI  - The combination of triiodothyronine (T3) and sertraline is not superior to
      sertraline monotherapy in the treatment of major depressive disorder.
AB  - OBJECTIVE: To determine whether the combination of triiodothyronine (T3) plus
      sertraline at treatment initiation confers greater antidepressant efficacy than
      sertraline plus placebo in patients with major depressive disorder. METHOD: Eight
      week, double blind, randomized placebo controlled clinical trial of 153 adult
      outpatients between 18 and 60 years of age, with DSM-IV defined major depressive
      disorder. Patients were treated with sertraline flexibly adjusted for
      tolerability and in a double blind fashion with placebo or T3 (25 MUg/day in week
      1 and increasing to 50 MUg/day in week 2). Response was defined categorically as
      50% reduction and total score less than 15 in 21-item Hamilton Rating Scale for
      Depression (HRSD-21) at week 8 and remission as HRSD-21 less than 8. RESULTS:
      There was no difference between treatment groups at final assessment; 65% of
      placebo and 61.8% of T3 treated subjects achieved response and 50.6% of placebo
      and 40.8% of T3 treated patients achieved remission. The mean daily dose at final
      assessment of sertraline and T3, respectively was 144.7 mg (+/- 48.7 mg) and 48.2
      MUg (+/- 7 MUg). Median time to response did not differ between treatment groups.
      Baseline thyroid function tests did not predict response to sertraline treatment
      or T3 augmentation. CONCLUSIONS: These results do not support the routine use of
      T3 to enhance or accelerate onset of antidepressant response in patients with
      major depressive disorder.

PMID- 22964162
TI  - Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large
      Dutch cohort.
AB  - Spastic paraplegia type 7 is an autosomal recessive neurodegenerative disorder
      mainly characterized by progressive bilateral lower limb spasticity and referred
      to as a form of hereditary spastic paraplegia. Additional disease features may
      also be observed as part of a more complex phenotype. Many different mutations
      have already been identified, but no genotype-phenotype correlations have been
      found so far. From a total of almost 800 patients referred for testing, we
      identified 60 patients with mutations in the SPG7 gene. We identified 14
      previously unreported mutations and detected a high recurrence rate of several
      earlier reported mutations. We were able to collect detailed clinical data for 49
      patients, who were ranked based on a pure versus complex phenotype, ataxia versus
      no ataxia and missense versus null mutations. A generally complex phenotype
      occurred in 69% of all patients and was associated with a younger age at onset
      (trend with P = 0.07). Ataxia was observed in 57% of all patients. We found that
      null mutations were associated with the co-occurrence of cerebellar ataxia (trend
      with P = 0.06). The c.1409 G > A (p.Arg470Gln) mutation, which was found
      homozygously in two sibs, was associated with a specific complex phenotype that
      included predominant visual loss due to optical nerve atrophy. Neuropathology in
      one of these cases showed severe degeneration of the optic system, with less
      severe degeneration of the ascending tracts of the spinal cord and cerebellum.
      Other disease features encountered in this cohort included cervical dystonia,
      vertical gaze palsy, ptosis and severe intellectual disability. In this large
      Dutch cohort, we seem to have identified the first genotype-phenotype correlation
      in spastic paraplegia type 7 by observing an association between the cerebellar
      phenotype of spastic paraplegia type 7 and SPG7 null alleles. An overlapping
      phenotypic presentation with its biological counterpart AFG3L2, which when
      mutated causes spinocerebellar ataxia type 28, is apparent and possibly suggests
      that abnormal levels of the SPG7 protein impact the function of the mitochondrial
      ATPases associated with diverse cellular activities-protease complex (formed by
      SPG7 and AFG3L2) in the cerebellum. In addition, a missense mutation in exon 10
      resulted in predominant optical nerve atrophy, which might suggest deleterious
      interactions of this SPG7 variant with its substrate OPA1, the mutated gene
      product in optic atrophy type 1. Functional studies are required to further
      investigate these interactions.

PMID- 22964163
TI  - Why is the molecular identification of the forensically important blowfly species
      Lucilia caesar and L. illustris (family Calliphoridae) so problematic?
AB  - Species of the fly genus Lucilia are commonly used in forensic investigations to
      estimate the postmortem interval (PMI). Two close-related species Lucilia caesar
      and L. illustris are difficult to identify. Previous studies showed that the
      mitochondrial cytochrome c oxidase subunit I (COI) marker could be used to
      identify many Lucilia species. However, mixed results were obtained for L. caesar
      and L. illustris due to some European specimens showing identical haplotypes.
      Here, we investigated 58 new European male specimens of L. illustris and L.
      caesar whose morphological identifications were checked and for which COI
      fragments were sequenced. In addition, two other mitochondrial (cytochrome c
      oxidase subunit II and 16S) and two nuclear (internal transcribed spacer 2 and
      28S ribosomal RNA) markers were obtained for a subset of these samples. For each
      marker, genetic divergence within each species was in the same range as between
      species, confirming the close relationship between both species. Moreover, for
      each of the gene fragments, both species shared at least one haplotype/genotype.
      Hence, none of the molecular markers tested could be used, alone or in
      combination, to discriminate between L. illustris and L. caesar.

PMID- 22964164
TI  - Dental age estimation in Spanish children.
AB  - The objective of this study was to apply the method for calculating dental age
      proposed by Demirjian et al. to a sample of Spanish children, followed by a
      comparison between their dental and chronological ages. This study also set out
      to create tables to convert specific dental age using the maturity data from our
      sample. This study was performed on a sample of 1010 orthopantograms taken of
      Spanish children (485 boys and 525 girls) aged 2-16. We found that the mean
      estimated dental age exceeded the mean chronological age in both boys and girls,
      with the mean difference being 0.87 and 0.55 years respectively. We adapted
      Demirjian's method to our study sample to obtain specific conversion tables and
      curves.

PMID- 22964165
TI  - CYP3A4 and CYP2C19 genetic polymorphisms and zolpidem metabolism in the Chinese
      Han population: a pilot study.
AB  - Zolpidem (ZPD) is an imidazopyridine hypnotic and little is known about the
      pharmacogenetics of ZPD. Our objective was to evaluate inter-individual genetic
      variation in conjunction with metabolic ratios of ZPD found in a toxicological
      analysis. Healthy individuals (n=300) were genotyped for CYP2D6, CYP2C19, CYP2C9,
      CYP3A4 and CYP1A2 by allele-specific primer extension followed by matrix-assisted
      laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS).
      Twenty-four Chinese volunteers were chosen and divided into the following four
      groups (n=6/group): group 1: CYP3A4*18 (wild-type, W), CYP2C19*2 (W); group 2:
      CYP3A4*18 (mutant, M), CYP2C19*2 (W); group 3: CYP3A4*18 (W), CYP2C19*2 (M); and
      group 4: CYP3A4*18 (M), CYP2C19*2 (M). ZPD and its major metabolites zolpidem 6
      carboxylic acid (ZCA) and zolpidem phenyl-4-carboxylic acid (ZPCA) were
      determined after oral administration of ZPD (10mg), using an UPLC-MS/MS method.
      Positive correlations between CYP3A4 and CYP2C19 alleles and ZPD metabolism were
      found. The results of this study show that CYP3A4*18 increases CYP3A4 activity
      while CYP2C19*2 reduces CYP2C19 activity; the latter mutation is associated with
      the poor metabolism of ZPD in the Chinese Han population. The results also
      suggest that genetic factors play a major role in the metabolism of individual
      drugs with implications for both forensic science and clinical pharmacogenetics.

PMID- 22964166
TI  - Alpha- and beta-asarone in herbal medicinal products. A case study.
AB  - The composition of pellets and tablets, which were sold as the preparations of
      Chinese natural medicine, was studied. The drugs were seized by the police due to
      the intoxication of a young woman. Analyses were performed by GC-MS (HP-5 ms
      column) and by HPLC (RP-18e Chromolith((r)) monolithic column). Diverse content
      of asarone isomers was found in the tested material. The dose of alpha-asarone
      ranged from 0.49 to 42.5 MUg per pellet, while its average concentration in the
      tablets was 51.4 MUg. Beta-asarone was not detected in the pellets with low
      content of alpha isomer (below 1 MUg), while its content in the remaining pellets
      ranged from 142 to 645 MUg. The tablets contained higher doses of beta-asarone
      (1526 MUg in average). The total content of asarones in most of the examined
      pellets and tablets exceeded 115 MUg, which is the maximum acceptable daily
      intake. Taking into account the dosage written on packages that ranged from
      several to more than ten pellets/tablets a day, one can assume that the intake of
      such doses of asarone might be health-threatening.

PMID- 22964168
TI  - Treatment decisions for metastatic castration-resistant prostate cancer
      progressing after docetaxel chemotherapy: the role of cabazitaxel in the
      continuum of care.

PMID- 22964170
TI  - Intestinal endometriosis: a sigmoid mass mimicking a colic neoplasm.

PMID- 22964169
TI  - Could interferon still play a role in metastatic renal cell carcinoma? A
      randomized study of two schedules of sorafenib plus interferon-alpha 2a
      (RAPSODY).
AB  - BACKGROUND: Sorafenib has proven efficacy in metastatic renal cell carcinoma
      (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both
      dose- and administration-schedule dependent. OBJECTIVE: To compare two different
      schedules of IFN combined with sorafenib. DESIGN, SETTING, AND PARTICIPANTS:
      Single-stage, prospective, noncomparative, randomized, open-label, multicenter,
      phase 2 study on previously untreated patients with mRCC and Eastern Cooperative
      Oncology Group performance status 0-2. INTERVENTION: Sorafenib 400mg twice daily
      plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU
      five times a week (Arm B). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary
      end points were progression-free survival (PFS) for each arm and safety. Data
      were evaluated according to an intent-to-treat analysis. RESULTS AND LIMITATIONS:
      A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo
      in Arm B (p=0.049) and the median duration of response was 8.5 and 19.2 mo,
      respectively (p=0.0013). Nine partial responses were observed in Arm A, and three
      complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%;
      p=0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable
      disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs
      16%; p=0.32) and hand-foot skin reactions (20% vs 18%). CONCLUSIONS: Sorafenib
      plus frequent low-dose IFN showed good efficacy and tolerability. Further
      investigations should be warranted to identify a possible positioning of this
      intriguing regimen (6% complete response rate) in the treatment scenario of mRCC.

PMID- 22964171
TI  - Laparoscopic repair of extraperitoneal urinary bladder rupture after blunt
      abdominal trauma.

PMID- 22964172
TI  - Helminth infestation of the appendix in a pregnant female.

PMID- 22964173
TI  - Wernicke's encephalopathy complicating acute necrotic pancreatitis.

PMID- 22964174
TI  - Partial pancreatic transection due to chiropractic manipulation.

PMID- 22964175
TI  - Arterioportal fistula as a rare cause of cryptogenic portal hypertension.

PMID- 22964176
TI  - Distant dermal metastases from head and neck cancers: pathways, prognosis, and
      palliation.

PMID- 22964178
TI  - Bouveret's syndrome: a rock in a hard place.

PMID- 22964177
TI  - Severe intra-abdominal bleeding plus large pneumoperitoneum after a procedure of
      prolapsed hemorrhoids.

PMID- 22964179
TI  - The lost foley catheter.

PMID- 22964180
TI  - Traumatic intraperitoneal rupture of an urachal leiomyosarcoma: unique
      presentation as hemorrhagic shock.

PMID- 22964181
TI  - What is the safer prognostic index of postoperative symptomatic hypocalcemia?

PMID- 22964182
TI  - Intrahepatic porcelain gallbladder: coexistence of pathologies.

PMID- 22964183
TI  - Successful surgical treatment of massive lower gastrointestinal bleeding in a
      patient with Wegener's granulomatosis.

PMID- 22964184
TI  - Squamous cell carcinoma as a complication of epidermolysis bullosa.

PMID- 22964185
TI  - Successful conservative treatment of chyle leak after total thyroidectomy and
      modified radical lymph node dissection.

PMID- 22964186
TI  - Repair of primary bowel obstruction resulting from a left paraduodenal hernia.

PMID- 22964187
TI  - Rectal cancer developing 44 years after ureterosigmoidostomy.

PMID- 22964188
TI  - Severe blunt liver injury complicated by Fitz-Hugh-Curtis syndrome.

PMID- 22964189
TI  - Extensive herniation and necrosis of the small and large bowel through the
      foramen of Winslow.

PMID- 22964190
TI  - Chain appendicitis.

PMID- 22964191
TI  - Tension pneumoperitoneum after traumatic gastric rupture.

PMID- 22964192
TI  - An unusual cause of abdominal pain in an elderly woman: obturator hernia.

PMID- 22964193
TI  - A feasible technique for intraoperative endoscopy of gastrointestinal bleeding:
      clothed endoscopy.

PMID- 22964194
TI  - Emphysematous cystitis after surgery for rectal cancer.

PMID- 22964195
TI  - The University of Tennessee Medical Center at Knoxville.
AB  - The University of Tennessee Medical Center at Knoxville hosts the University
      Health Services and the University of Tennessee Graduate School of Medicine.
      Founded in 1956, the center along with the Department of Surgery has grown in
      size and in academic stature to become an outstanding  tertiary clinical, medical
      education, and research center.

PMID- 22964196
TI  - Baron Guillaume Dupuytren: when brilliance combats professionalism.

PMID- 22964197
TI  - A single institution's experience and journey with over 1000 laparoscopic
      fundoplications for gastroesophageal reflux disease.
AB  - There have been great advances in laparoscopic surgery for gastroesophageal
      reflux disease (GERD), including laparoendoscopic single-site (LESS) surgery.
      This study details our experience with over 1000 patients undergoing
      fundoplication for GERD and the journey therein. A total of  1078 patients have
      been prospectively followed after fundoplication. Patients scored the
      frequency/severity of symptoms using a Likert scale (0 = never/not bothersome to
      10 = always/very bothersome). We compared the outcomes of the first and last 100
      patients. Median data are reported. Of  1078 patients, 943 underwent conventional
      laparoscopic fundoplication and 135, most recently, underwent LESS
      fundoplication. Before fundoplication, patients noted frequent/severe symptoms
      (e.g., heartburn: frequency = 8, severity = 8). Fundoplication ameliorated
      frequency/severity of symptoms  (e.g., heartburn: frequency = 2, severity = 0;
      less than preoperatively, P < 0.05). Relative to our first 100 patients, patients
      after LESS surgery had similar symptom control (e.g., heartburn: frequency =
      eight to two vs eight to zero, severity = eight to one vs six  to one) but had
      shorter hospital stays (2 vs 1 day, P < 0.05) and had no apparent scars.
      Laparoscopic fundoplication provides durable and efficacious treatment for GERD;
      long-term symptom resolution and patient satisfaction support its continued
      application. The advent of  LESS surgery advances surgeons' abilities to provide
      safe and salutary care while promoting cosmesis.

PMID- 22964198
TI  - The effects of repeat laparoscopic surgery on the treatment of complications
      resulting from laparoscopic surgery.
AB  - Laparoscopic surgery is frequently applied in the operative management of
      appendicitis and symptomatic cholelithiasis because it is a minimally invasive
      procedure. There are, however, some complications of laparoscopic cholecystectomy
      (LC) and laparoscopic appendectomy (LA) that result  in the need for reoperation.
      In the current study, we examine the effects of repeat laparoscopic surgery on
      the treatment of complications arising from LC/LA. From April 2005 to March 2011,
      we examined a cohort of patients who had received LC or LA and experienced
      complications that required  reoperations. We focused on patients with
      postoperative hemorrhages, postoperative peritonitis, early postoperative small
      bowel obstructions (EPSBO), and biliary complications (after LC) who were treated
      through a repeat laparoscopic approach. The general demographics of the patients,
      their  postoperative complications, procedures for selecting the appropriate
      reoperation method, and repeat laparoscopic findings are described in detail.
      During the 6-year period examined, 1608 patients received LC and 1486 patients
      received LA at the hospitals participating in this study. In patients  with
      complications requiring reoperation, the repeat laparoscopic approach was
      performed successfully (without the need for further laparotomy) in 50 per cent
      of the patients with postoperative hemorrhage (2 of 4), 50 per cent of the
      patients with postoperative peritonitis (2 of 4), 75 per  cent of the EPSBO
      patients (3 of 5), and 50 per cent the of patients with biliary complications (1
      of 2). The repeat laparoscopic approach is an appropriate method for the
      management of complications arising from laparoscopic surgery. In patients with
      postoperative hemorrhage, laparoscopic  hemostasis and hematoma evacuations can
      be performed while maintaining stable hemodynamics. In addition, laparoscopic
      approaches are also feasible for selective post-LC ductal injuries, EPSBO, and
      unconfirmed diagnoses of peritonitis after laparoscopic surgery.

PMID- 22964199
TI  - Accurate assessment of breast volume by computed tomography using three
      dimensional imaging device.
AB  - Preoperative assessment of breast volume could contribute significantly to the
      planning of breast reconstructive surgery. However, breast volume measurements
      are not carried out on a routine basis, because there is still no commonly
      accepted standard method for such measurements. In  the current study, we
      assessed whether routine computed tomography (CT) of the chest using a three
      dimensional device could provide accurate estimation of breast volumes in
      patients with breast cancer. Ten consecutive patients and 11 breasts with breast
      cancer that underwent mastectomy with  immediate breast reconstruction were
      enrolled in this study. In each case, a three-dimensional image was constructed
      according to the CT data using a volume-rendering technique. Computed breast
      volumes were compared with known breast volumes obtained from surgical specimens.
      The mean breast  volume of surgical specimens was 324.1 +/- 173.5 mL. The mean
      breast volume value was established to be 351.6 +/- 174.3 mL with three
      dimensional CT in a novel method. There was a strong linear association between
      breast volumes of surgical specimens and breast volumes measured by  the three
      dimensional CT method when using a Pearson correlation (r = 0.985, P < 0.001).
      Our results suggest that the calculation of breast volume using three-dimensional
      CT is accurate enough to have a significant clinical benefit in planning
      reconstructive breast surgery. This method  can help the surgeon predict the
      esthetic effect of various breast surgeries and guide the choice of the most
      appropriate implant preoperatively.

PMID- 22964200
TI  - Low-volume resuscitation for severe intraoperative hemorrhage: a step in the
      right direction.
AB  - The impact on outcomes resulting from crystalloids used with hemostatic close
      ratio resuscitation (HCRR) in intraoperative hemorrhage (IOH) has not been
      analyzed. We hypothesize a survival advantage in patients with IOH managed with a
      low-volume resuscitation (LVR) protocol during HCRR.  A 4-year case-control study
      was conducted to determine the impact on mortality of LVR versus conventional
      resuscitation efforts (CRE) during HCRR. A total of 45 patients managed with a
      HCRR + LVR protocol (combination Hextend(r) and 3% hypertonic saline) and 55
      historical cohorts  managed with HCRR + CRE (lactated Ringer's) were included.
      Patient demographics, number of intraoperative units of packed red blood cells
      (PRBCs) and fresh-frozen plasma (FFP) received, and FFP:PRBC ratio were similar
      between groups. The mean intraoperative fluid volume was 0.76 L in  the HCRR +
      LVR group versus 4.7 L in the HCRR + CRE group (P = 0.003). In a linear
      regression model HCRR + LVR versus HCRR + CRE, mean trauma intensive care unit
      length of stay was 6 versus 11 days (P = 0.009); 30-day overall mortality was
      11.1 versus  32.7 per cent (P = 0.009); perioperative mortality was 2.2 to 10.9
      per cent (P = 0.13); and intensive care unit mortality 8.8 to 21.8 per cent (P =
      0.07). LVR protocol conveyed a survival benefit to patients undergoing HCRR (odds
      ratio for mortality, 0.07 [95% confidence  interval 0.07-0.54]). This is the
      first civilian study to analyze the impact of LVR in patients managed with HCRR
      during IOH. Patients with IOH managed with HCRR and a predefined LVR protocol
      with Hextend(r) and 3 per cent hypertonic saline had an overall survival
      advantage and shorter  trauma intensive care unit length of stay. LVR can be an
      effective alternative to CRE when used in combination with HCRR in patients with
      IOH.

PMID- 22964201
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the
      treatment of peritoneal carcinomatosis: initial experience in Oaxaca, Mexico.
AB  - Peritoneal carcinomatosis (PC) has been traditionally considered a terminal
      disease with median survivals reported in the literature of 6 to 12 months.
      Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are
      playing an ever increasing role in the treatment of  these patients. Excellent
      results have been achieved in well-selected patients but there is a very steep
      learning curve when starting a new program. A program for peritoneal surface
      malignancies in which patients with PC of gastrointestinal or gynecological
      origin were treated using multimodality  therapy with combinations of systemic
      therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at
      "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the
      results of our initial experience. From December 2007 to February 2011, 26
      patients  were treated with CRS and HIPEC. There were 21 female patients. Most
      common indication (46%) was recurrent ovarian cancer. Mean duration of surgery
      was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%)
      patients had a complete cytoreduction. Major morbidity and mortality  rates were
      19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean
      follow-up of 20 months, median survival has not been reached. Rigorous
      preoperative workup, strict selection criteria, and mentoring from an experienced
      cytoreductive surgeon are mandatory and extremely  important when starting a
      center for PC.

PMID- 22964202
TI  - Variations in the locations of the recurrent laryngeal nerve in relation to the
      ligament of Berry.
AB  - Injury to the recurrent laryngeal nerve (RLN) is one of the most common
      iatrogenic complications of thyroid surgery. The anatomical course of the nerve
      also increases its susceptibility to injury and many variations have been
      documented in the literature. The topographical relationship  of the RLN to the
      ligament of Berry has been extensively studied over the past decades. The
      consensus in the literature is divided with several authors reporting the nerve
      to be embedded within the ligament and others reporting a constant finding of the
      nerve being posterolateral to the ligament.  A new operative concept has been
      recently introduced as a possible resolution for the conflicting reports among
      authors. Further investigations are needed, however, to assess its reliability
      and overall effects on clinical outcomes.

PMID- 22964203
TI  - Functional outcomes and quality of life after anorectal surgery.
AB  - There is a paucity of information examining quality of life (QOL) and functional
      results after anorectal surgery. We aim to prospectively evaluate postoperative
      QOL, pain, functional outcomes, and satisfaction for a large cohort of patients
      undergoing anorectal surgery. Data were prospectively  accrued for consecutive
      patients undergoing anorectal operations from June 2009 to September 2010.
      Preoperative and postoperative electronic questionnaires were completed. QOL was
      evaluated by the European QOL index (EQ-5D) and functional results with the Fecal
      Incontinence Severity Index  (FISI). Satisfaction was assessed: 1) Are you
      satisfied with surgery? 2) Would you recommend surgery to others? Responses were
      reported: 1 to 5 (1 = not at all; 5 = a lot). Pain was scored: 1 (no pain) to 10
      (worst). One hundred ninety-five patients, 111 (56.9%) females, median age 44
      years  (range, 18 to 93 years), underwent anorectal surgery for abscess,
      condyloma, fissure, fistula, hemorrhoids, incontinence, pilonidal disease, pouch
      problems, tumors, and prolapse. Overall, pain improved significantly with
      improved QOL (P = 0.03). This correlated with overall postoperative  satisfaction
      (92.4%). A total of 87.7 per cent of patients would recommend their surgery to
      others. The FISI was similar pre- and postoperatively (P = 0.18) and did not
      worsen postoperatively irrespective of surgical indication and procedure. Most
      patients were satisfied after anorectal  surgery, which correlated with improved
      pain and QOL. Functional outcomes did not worsen. This will help counsel patients
      preoperatively and allay anxiety about postoperative function.

PMID- 22964204
TI  - The value of vacuum-assisted closure in septic patients treated with laparostomy.
AB  - The ideal method of temporary abdominal closure (TAC) should allow rapid closure,
      easy maintenance, and wound repair with minimal tissue damage. The aim of this
      retrospective study is to compare open abdomen outcomes between patients managed
      with vacuum-assisted closure (VAC), and patients  managed with other methods of
      TAC, when septic abdomen is present. Two groups of patients with septic open
      abdomen: 27 treated with VAC versus 31 treated with other techniques of TAC. We
      studied open abdomen duration, number of dressing changes, re-exploration rate,
      successful abdominal  closure rate, overall mortality, and development of
      enteroatmospheric fistulas. The VAC device demonstrated its superiority
      concerning open abdomen duration (P < 0.001), number of dressing changes (P <
      0.001), re-exploration rate (P < 0.002), successful abdominal  closure rate (P <
      0.0001), and development of enteroatmospheric fistulas (P < 0.00001). Compared
      with other methods of TAC, our experience with the VAC device demonstrated its
      advantages concerning clinical feasibility. The high rates of direct fascia
      closure with an acceptable  rate of ventral hernias are further benefits of this
      technique.

PMID- 22964205
TI  - Damage control immunoregulation: is there a role for low-volume hypertonic saline
      resuscitation in patients managed with damage control surgery?
AB  - Hypertonic saline (HTS) is beneficial in the treatment of head-injured patients
      as a result of its potent cytoprotective effects on various cell lines. We
      hypothesize that low-volume resuscitation with 3 per cent HTS, when used after
      damage control surgery (DCS), improves outcomes compared  with standard
      resuscitation with isotonic crystalloid solution (ICS). This is a 4-year
      retrospective review from two Level I trauma centers. Patients included had 10
      units or more of packed red blood cells during initial DCS. On arrival to the
      trauma intensive care unit (TICU), patients were  resuscitated with low-volume 3
      per cent HTS or with conventional ICS. A cohort analysis was performed comparing
      resuscitation strategies. Univariate analysis of continuous data was done with
      Student t test followed by multivariate analysis. Of 188 patients included, 76
      were in the low-volume  HTS group and 112 in the ICS group. Demographics were
      similar between the groups. Over the next 48 hours after DCS in HTS versus ISC
      groups, intravenous fluids were given: 1920 +/- 455 mL versus 8400 +/- 1200 mL (P
      < 0.0001); urine output was 4320 +/-  480 mL versus 1940 +/- 480 mL(P < 0.0001);
      mean TICU length of stay was 10 +/- 8 versus 16 +/- 15 days (P < 0.01);
      prevalence of acute respiratory distress syndrome was 4.0 versus 13.4 per cent (P
      = 0.02); sepsis was 6.6 versus  15.2 per cent (P = 0.06); multisystem organ
      failure was: 2.6 versus 16.1 per cent (P < 0.01); and 30-day mortality was 5.3
      versus 15.2 per cent (P = 0.03). There was no difference for prevalence of renal
      failure at 5.3 versus 3.6 per cent (P  = 0.58). Low-volume resuscitation with HTS
      administered after DCS on arrival to the TICU may have a protective effect on the
      polytrauma patient. We believe that this study demonstrates a role for low-volume
      resuscitation with HTS to improve outcomes in patients undergoing DCS.

PMID- 22964207
TI  - Treatment and outcomes of iatrogenic colon perforations at a community teaching
      hospital.
AB  - Despite the growing expertise in colonoscopy, it remains subject to
      complications. The previously published rate of colonoscopic perforation is 0.82
      per 1000 examinations. The objective of this study was to describe the experience
      and management of colonoscopic perforations. A retrospective  review of cases
      from a database of surgical complications was searched for perforations
      postcolonoscopy from January 1, 2001, to December 31, 2010 at a 527-bed community
      teaching hospital. Eighteen patients were identified, 11 of whom underwent
      examination at our institution. Ages ranged from  40 to 91 years with a mean age
      of 71 years. Eleven of the 18 patients were female and seven were male. Main
      outcome measures were treatment approach, treatment complications, and mortality.
      A total of 18 patients were identified in this database. Of these 18 patients, 11
      underwent colonoscopy  at our institution. During the studied time period, 7578
      colonoscopies were performed at our hospital. The majority of the perforations
      were located in the rectosigmoid colon. Seventeen patients were treated with
      surgical exploration of the abdomen. Ten patients experienced complications
      postoperatively.  There were two deaths in our series. Only cases in which the
      colonoscopy was performed at our institution were used when making incidence
      calculations. The incidence of perforation in our series was significantly higher
      than previously reported rates. When the perforation was discovered and  treated
      within 24 hours, the patient was rescued. Timely recognition of surgical
      complications is critical in preventing patient mortality.

PMID- 22964206
TI  - Midterm impact of sleeve gastrectomy, calibrated with a 50-Fr bougie, on weight
      loss, glucose homeostasis, lipid profiles, and comorbidities in morbidly obese
      patients.
AB  - Bariatric surgery has been shown to be effective in achieving and maintaining
      weight change and reducing obesity-related comorbidities. Recent reports have
      shown that sleeve gastrectomy could have similar resolution rates of the
      metabolic syndrome than Roux-Y bypass after a short-term  follow-up of 1 year.
      Most surgeons calibrate the sleeve with 32-Fr to 40-Fr bougies. There is little
      mid- and long-term information available about the evolution of these
      comorbidities with this procedure and with calibration of the sleeve with a 50-Fr
      bougie. A retrospective study of all  the morbidly obese patients undergoing
      laparoscopic sleeve gastrectomy, calibrated with a 50-Fr bougie, as bariatric
      procedure between October 2007 and September 2009 was performed. Mean excessive
      body mass index loss was 76.9 per cent after 1 year and 79.9 per cent after 2
      years. After surgery,  83.3 per cent of patients with Type 2 diabetes mellitus
      discontinued their hypoglycemic medication at 1 month. All the patients with
      hypertension discontinued antihypertensive drugs at 6 months. One hundred per
      cent of patients with hypertriglyceridemia discontinued their hypolipidemic drugs
      at 3 months. Glucose levels decreased significantly 3 months after surgery (mean
      reduction of 24.7 mg/dL; 95% confidence interval [CI], 8.8 to 40.7; P = 0.003).
      Triglyceride levels decreased 3 months after surgery (mean reduction of 54.4
      mg/dL; 95% CI, 22.8 to 86.1; P = 0.004).  High-density lipoprotein (HDL)
      cholesterol increased significantly after 12 months (increase of 16.7 mg/dL; 95%
      CI, 11.7 to 21.7; P < 0.001). The changes observed were maintained 24 months
      after surgery. Sleeve gastrectomy, calibrated with a 50-Fr bougie, significantly
      reduced glucose  and triglyceride levels and the cardiovascular risk predictor
      triglyceride/HDL ratio and increased HDL levels after surgery and maintained them
      under normal ranges for at least 2 years.

PMID- 22964208
TI  - The role of repeat computed tomography scan in the evaluation of blunt bowel
      injury.
AB  - The precise role of repeat abdominal computed tomography (CT) imaging in the
      diagnosis and management of bowel injury is unclear. We reviewed 540 patients
      with blunt abdominal trauma managed at a Level II trauma center over a 5-year
      period to better define the role of repeat imaging.  One hundred patients had a
      repeat abdominal CT scan within 72 hours of admission. These patients were young
      with multisystem injuries (mean +/- standard deviation age, 34 +/- 15 years;
      Injury Severity Score, 21 +/- 12; Glasgow Coma Score [GCS], 12 +/- 5). There were
      14  patients with bowel injuries. All bowel-injured patients survived without
      abdominal morbidity. Time to repeat CT was shortest in the bowel injured group
      (20 +/- 10 hours). The repeat CT was most helpful in patients with significant
      closed head injury (mean GCS, 3 +/- 1) and in those  with occult bowel injury.
      The repeat scan resulted in a change in clinical management in 26 patients.
      Regarding the presence of bowel perforation, the follow-up scan enhanced
      sensitivity from 30 to 82 per cent. The repeat abdominal CT is best used
      selectively in patients with blunt abdominal  trauma and can provide clinically
      useful information to exclude bowel injury.

PMID- 22964209
TI  - External branch of the superior laryngeal nerve: applied surgical anatomy and
      implications in thyroid surgery.
AB  - The external branch of the superior laryngeal nerve (EBSLN) is the only motor
      supply to the cricothyroid muscle and has an important role during phonation in
      high frequencies. Iatrogenic injury of the EBSLN, most commonly during thyroid
      surgery, is associated with varying levels of  alterations in phonation, which
      may have an impact on a patient's life, especially when his or her career depends
      on the full range of voice. EBSLN injury incidence after thyroid surgery ranges
      widely in the literature (0 to 58%). Despite this wide variation, it appears that
      EBSLN injury  is a not uncommon, and frequently overlooked, complication of
      thyroid surgery. An in-depth knowledge of the surgical anatomy of the EBSLN is
      therefore required from the part of the operating surgeon to protect this nerve
      during thyroid surgery.

PMID- 22964210
TI  - Does androgen receptor have a prognostic role in patients with
      estrogen/progesterone-negative and c-erbB-2-positive breast cancer?
AB  - Recently, it has been shown that androgen and androgen receptor (AR) also have an
      important role in the pathogenesis and outcome of breast cancer. However, their
      significance in different subtypes of breast cancer is still under investigation.
      The aim of this study was to study the  effects of AR on clinicopathological
      features and prognosis in patients with estrogen and progesterone receptor
      (ER/PR)-negative, HER2-positive breast cancer. Tumor paraffin-embedded blocks
      from archives were used for AR study. Data of patients with ER/PR-negative and
      HER2-positive breast  cancer diagnosed at our institute between 1999 and 2010
      were recorded and analyzed retrospectively. We studied 36 patients with ER/PR
      negative and HER2-positive breast cancer for AR status. Sixteen of them (44.4%)
      showed AR positivity. The median age was 47 and 56 years for AR-negative and  
      positive patients, respectively (P = 0.03). The number of postmenopausal patients
      was higher in the AR-positive than -negative group (56 vs 30%) (P = 0.01). Other
      demographic data were similar in both group. Histopathological parameters and
      tumor and nodal stages were  similar in both groups. Trastuzumab treatment was
      more frequently given to AR-positive than -negative patients (94 vs 44%) (P =
      0.01). Median follow-up was 47.1 and 34.7 months in AR-negative and -positive
      groups, respectively (P = 0.03). Relapse occurred in six and four  patients in AR
      negative and -positive groups. Median progression-free survival (PFS) was similar
      in both groups (15.7 and 19.6 months in AR-negative and -positive patients,
      respectively; P = 0.56). Two patients died at 23.4 and 46 months of follow-up in
      the AR-negative group. There  were no deaths in the AR-positive group. Overall
      survival analyses were not done as a result of an unmet number of events. Median
      PFS was similar in AR-positive and -negative in that group of patients with ER/PR
      negative and HER2-positive breast cancer. However AR-positive patients were more 
      frequently postmenopausal, older, and positive for lymphovascular space invasion.
      More frequently applied trastuzumab in the AR-positive group might have an effect
      on the similarity of PFS between the two groups. Studies with higher numbers in
      this subset of patients with breast cancer will  give more robust data.

PMID- 22964212
TI  - Personal watercraft injuries on noncoastal waterways.

PMID- 22964211
TI  - Project Prescription for Hope (RxH): trauma surgeons and community aligned to
      reduce injury recidivism caused by violence.
AB  - The recidivism rate for violent injuries in the United States has been reported
      as high as 45 per cent. Based on a retrospective review, the 5-year recidivism
      rate at the Indiana University/Wishard Trauma Center is 31 per cent, and the 1
      year recidivism rate is 8.7 per cent. Individuals  who have been admitted with a
      violent injury are screened by one of the Prescription for Hope (RxH) support
      specialists (SS). If the individual consents to participate, the SS conducts an
      in-depth assessment of risk factors. The SS and participant identify personal
      goals and develop a tailored  service plan, which is outlined in a formalized
      agreement. In the first year of the RxH program (June 1, 2009, to May 31, 2010),
      64 patients were enrolled. The most-often referred community services are in the
      category of social integration (84%). The SS have a 99 per cent success rate in 
      getting clients to initiate services; 82 per cent have completed the services and
      12 per cent are still using the services. As of the time of this writing, 34
      subjects have been in RxH for at least 1 year. One patient returned to the trauma
      center in September 2010 with a repeat violent injury;  this represents a 2.9 per
      cent 1-year recidivism rate. In the first 12 months of our program we did not
      have any participants return with a violent injury (0% recidivism), and we have
      only had one patient return to date. We conclude that the RxH SS model may play a
      significant role in decreasing  the recidivism of violent injuries.

PMID- 22964213
TI  - A case-control study of the approach for hand-assisted laparoscopic right
      hemicolectomy: medial-to-lateral versus lateral-to-medial.

PMID- 22964214
TI  - Rectus sheath hematoma causing ileocecal perforation.

PMID- 22964215
TI  - Intravenous ultrasound-directed superior vena cava filter placement without
      contrast.

PMID- 22964216
TI  - The promotion of laparoscopic suturing competence among residents.

PMID- 22964217
TI  - Isolated extrahepatic bile duct injury after blunt trauma abdomen.

PMID- 22964218
TI  - Enterobacter cancerogenus in trauma.

PMID- 22964219
TI  - Induction of caspase 8 and reactive oxygen species by ruthenium-derived
      anticancer compounds with improved water solubility and cytotoxicity.
AB  - Organometallic compounds which contain metals, such as ruthenium or gold, have
      been investigated as a replacement for platinum-derived anticancer drugs. They
      often show good antitumor effects, but the identification of their precise mode
      of action or their pharmacological optimization is still challenging. We have
      previously described a class of ruthenium(II) compounds with interesting
      anticancer properties. In comparison to cisplatin, these molecules have lower
      side effects, a reduced ability to interact with DNA, and they induce cell death
      in absence of p53 through CHOP/DDIT3. We have now optimized these molecules by
      improving their cytotoxicity and their water solubility. In this article, we
      demonstrate that by changing the ligands around the ruthenium we modify the
      ability of the compounds to interact with DNA. We show that these optimized
      molecules reduce tumor growth in different mouse models and retain their ability
      to induce CHOP/DDIT3. However, they are more potent inducers of cancer cell death
      and trigger the production of reactive oxygen species and the activation of
      caspase 8. More importantly, we show that blocking reactive oxygen species
      production or caspase 8 activity reduces significantly the activity of the
      compounds. Altogether our data suggest that water-soluble ruthenium(II)-derived
      compounds represent an interesting class of molecules that, depending on their
      structures, can target several pro-apoptotic signaling pathways leading to
      reactive oxygen species production and caspase 8 activation.

PMID- 22964220
TI  - Gli family transcription factors are drivers of patupilone resistance in ovarian
      cancer.
AB  - Epothilones constitute a novel class of antitubulin agents that are active in
      patients who relapse after treatment with other chemotherapeutics. This study
      investigated the molecular mechanisms leading to the onset of epothilone-B
      (patupilone) resistance in ovarian cancer. Results demonstrated that the Gli
      family of transcription factors was overexpressed in resistant cells and that
      treatment with a specific Gli1 inhibitor (GANT58) made cells more susceptible to
      treatment, partially reversing drug resistance. We also demonstrated that Gli1
      knockdown halted growth in resistant cells that were exposed to patupilone,
      confirming that Gli1 is capable of directly mediating epothilone-B resistance.
      Another observation from our research was that patupilone-resistant cells
      produced HGF and acquired characteristics of a mesenchymal phenotype. However,
      HGF silencing alone was not capable of converting the drug-resistant phenotype to
      a susceptible one, and in this case we demonstrated that Gli1 overexpression led
      to an increase in HGF, establishing a functional link between Gli1 and HGF. These
      results demonstrated that Gli1 played a key role in driving resistance to
      patupilone, suggesting that the combination of epothilones and Gli1-targeted
      agents could be exploited to improve outcomes in ovarian cancer patients
      resistant to standard treatments.

PMID- 22964221
TI  - Downregulated gene expression of TGF-betas in diabetic oral wound healing.
AB  - BACKGROUND: Healing of tooth extraction sockets in poorly controlled diabetic
      patients is often delayed and accompanied by severe infection. The exact cellular
      and molecular mechanisms underlying the pathogenesis of this complication are
      still not fully understood. OBJECTIVES: The purpose of this study was to
      investigate molecular changes associated with delayed oral wound healing in
      diabetes. MATERIALS AND METHODS: Six to eight weeks old male type 2 diabetes and
      age matched control inbred mice were used and maxillary molar tooth extractions
      were performed. At 4 and 7 days after tooth extraction, the edentulous mucosa of
      the mice were harvested, and analyzed for histology and gene expression of key
      wound healing factors. RESULTS: In the diabetic model, histological analysis
      showed that epithelial tissue migration for wound closure was delayed after tooth
      extraction compared to the control. Quantitative real-time PCR revealed that
      expression of the TGF-beta1, TGF-beta2, TGF-beta3, TGFbetaRII and TGFbetaRIII
      genes was significantly downregulated in the diabetic model at 4 and 7 days after
      tooth extraction. CONCLUSION: These results suggest that delayed wound healing of
      oral mucosa in diabetes may be associated with decreased expression levels of
      these regulatory genes which play important roles in controlling epithelial wound
      closure.

PMID- 22964222
TI  - Analysis of intact monoclonal antibody IgG1 by electron transfer dissociation
      Orbitrap FTMS.
AB  - The primary structural information of proteins employed as biotherapeutics is
      essential if one wishes to understand their structure-function relationship, as
      well as in the rational design of new therapeutics and for quality control. Given
      both the large size (around 150 kDa) and the structural complexity of intact
      immunoglobulin G (IgG), which includes a variable number of disulfide bridges,
      its extensive fragmentation and subsequent sequence determination by means of
      tandem mass spectrometry (MS) are challenging. Here, we applied electron transfer
      dissociation (ETD), implemented on a hybrid Orbitrap Fourier transform mass
      spectrometer (FTMS), to analyze a commercial recombinant IgG in a liquid
      chromatography (LC)-tandem mass spectrometry (MS/MS) top-down experiment. The
      lack of sensitivity typically observed during the top-down MS of large proteins
      was addressed by averaging time-domain transients recorded in different LC-MS/MS
      experiments before performing Fourier transform signal processing. The results
      demonstrate that an improved signal-to-noise ratio, along with the higher
      resolution and mass accuracy provided by Orbitrap FTMS (relative to previous
      applications of top-down ETD-based proteomics on IgG), is essential for
      comprehensive analysis. Specifically, ETD on Orbitrap FTMS produced about 33%
      sequence coverage of an intact IgG, signifying an almost 2-fold increase in IgG
      sequence coverage relative to prior ETD-based analysis of intact monoclonal
      antibodies of a similar subclass. These results suggest the potential application
      of the developed methodology to other classes of large proteins and biomolecules.

PMID- 22964223
TI  - Mass spectrometry reveals differences in stability and subunit interactions
      between activated and nonactivated conformers of the (alphabetagammadelta)4
      phosphorylase kinase complex.
AB  - Phosphorylase kinase (PhK), a 1.3 MDa enzyme complex that regulates
      glycogenolysis, is composed of four copies each of four distinct subunits (alpha,
      beta, gamma, and delta). The catalytic protein kinase subunit within this complex
      is gamma, and its activity is regulated by the three remaining subunits, which
      are targeted by allosteric activators from neuronal, metabolic, and hormonal
      signaling pathways. The regulation of activity of the PhK complex from skeletal
      muscle has been studied extensively; however, considerably less is known about
      the interactions among its subunits, particularly within the non-activated versus
      activated forms of the complex. Here, nanoelectrospray mass spectrometry and
      partial denaturation were used to disrupt PhK, and subunit dissociation patterns
      of non-activated and phospho-activated (autophosphorylation) conformers were
      compared. In so doing, we have established a network of subunit contacts that
      complements and extends prior evidence of subunit interactions obtained from
      chemical crosslinking, and these subunit interactions have been modeled for both
      conformers within the context of a known three-dimensional structure of PhK
      solved by cryoelectron microscopy. Our analyses show that the network of contacts
      among subunits differs significantly between the nonactivated and phospho
      activated conformers of PhK, with the latter revealing new interprotomeric
      contact patterns for the beta subunit, the predominant subunit responsible for
      PhK's activation by phosphorylation. Partial disruption of the phosphorylated
      conformer yields several novel subcomplexes containing multiple beta subunits,
      arguing for their self-association within the activated complex. Evidence for the
      theoretical alphabetagammadelta protomeric subcomplex, which has been sought but
      not previously observed, was also derived from the phospho-activated complex. In
      addition to changes in subunit interaction patterns upon phospho-activation, mass
      spectrometry revealed a large change in the overall stability of the complex,
      with the phospho-activated conformer being more labile, in concordance with
      previous hypotheses on the mechanism of allosteric activation of PhK through
      perturbation of its inhibitory quaternary structure.

PMID- 22964224
TI  - Temporal profiling of lapatinib-suppressed phosphorylation signals in EGFR/HER2
      pathways.
AB  - Lapatinib is a clinically potent kinase inhibitor for breast cancer patients
      because of its outstanding selectivity for epidermal growth factor receptor
      (EGFR) and EGFR2 (also known as HER2). However, there is only limited information
      about the in vivo effects of lapatinib on EGFR/HER2 and downstream signaling
      targets. Here, we profiled the lapatinib-induced time- and dose-dependent
      phosphorylation dynamics in SKBR3 breast cancer cells by means of quantitative
      phosphoproteomics. Among 4953 identified phosphopeptides from 1548 proteins, a
      small proportion (5-7%) was regulated at least twofold by 1-10 MUm lapatinib. We
      obtained a comprehensive phosphorylation map of 21 sites on EGFR/HER2, including
      nine novel sites on HER2. Among them, serine/threonine phosphosites located in a
      small region of HER2 (amino acid residues 1049-1083) were up-regulated by the
      drug, whereas all other sites were down-regulated. We show that cAMP-dependent
      protein kinase is involved in phosphorylation of this particular region of HER2
      and regulates HER2 tyrosine kinase activity. Computational analyses of
      quantitative phosphoproteome data indicated for the first time that protein
      protein networks related to cytoskeletal organization and
      transcriptional/translational regulation, such as RNP complexes (i.e. hnRNP,
      snRNP, telomerase, ribosome), are linked to EGFR/HER2 signaling networks. To our
      knowledge, this is the first report to profile the temporal response of
      phosphorylation dynamics to a kinase inhibitor. The results provide new insights
      into EGFR/HER2 regulation through region-specific phosphorylation, as well as a
      global view of the cellular signaling networks associated with the anti-breast
      cancer action of lapatinib.

PMID- 22964226
TI  - Testing isotopic labeling with [13C6]glucose as a method of advanced glycation
      sites identification.
AB  - The Maillard reaction occurring between reducing sugars and reactive amino groups
      of biomolecules leads to the formation of a heterogeneous mixture of compounds:
      early, intermediate, and advanced glycation end products (AGEs). These compounds
      could be markers of certain diseases and of the premature aging process.
      Detection of Amadori products can be performed by various methods, including
      MS/MS techniques and affinity chromatography on immobilized boronic acid.
      However, the diversity of the structures of AGEs makes detection of these
      compounds more difficult. The aim of this study was to test a new method of AGE
      identification based on isotope (13)C labeling. The model protein (hen egg
      lysozyme) was modified with an equimolar mixture of [(12)C(6)]glucose and
      [(13)C(6)]glucose and then subjected to reduction of the disulfide bridges
      followed by tryptic hydrolysis. The digest obtained was analyzed by LC-MS. The
      glycation products were identified on the basis of characteristic isotopic
      patterns resulting from the use of isotopically labeled glucose. This method
      allowed identification of 38 early Maillard reaction products and five different
      structures of the end glycation products. This isotopic labeling technique
      combined with LC-MS is a sensitive method for identification of advanced
      glycation end products even if their chemical structure is unknown.

PMID- 22964225
TI  - Molecular characterization of EGFR and EGFRvIII signaling networks in human
      glioblastoma tumor xenografts.
AB  - Glioblastoma multiforme (GBM) is a malignant primary brain tumor with a mean
      survival of 15 months with the current standard of care. Genetic profiling
      efforts have identified the amplification, overexpression, and mutation of the
      wild-type (wt) epidermal growth factor receptor tyrosine kinase (EGFR) in ~ 50%
      of GBM patients. The genetic aberration of wtEGFR is frequently accompanied by
      the overexpression of a mutant EGFR known as EGFR variant III (EGFRvIII, de2
      7EGFR, DeltaEGFR), which is expressed in 30% of GBM tumors. The molecular
      mechanisms of tumorigenesis driven by EGFRvIII overexpression in human tumors
      have not been fully elucidated. To identify specific therapeutic targets for
      EGFRvIII driven tumors, it is important to gather a broad understanding of
      EGFRvIII specific signaling. Here, we have characterized signaling through the
      quantitative analysis of protein expression and tyrosine phosphorylation across a
      panel of glioblastoma tumor xenografts established from patient surgical
      specimens expressing wtEGFR or overexpressing wtEGFR (wtEGFR+) or EGFRvIII
      (EGFRvIII+). S100A10 (p11), major vault protein, guanylate-binding protein
      1(GBP1), and carbonic anhydrase III (CAIII) were identified to have significantly
      increased expression in EGFRvIII expressing xenograft tumors relative to wtEGFR
      xenograft tumors. Increased expression of these four individual proteins was
      found to be correlated with poor survival in patients with GBM; the combination
      of these four proteins represents a prognostic signature for poor survival in
      gliomas. Integration of protein expression and phosphorylation data has uncovered
      significant heterogeneity among the various tumors and has highlighted several
      novel pathways, related to EGFR trafficking, activated in glioblastoma. The
      pathways and proteins identified in these tumor xenografts represent potential
      therapeutic targets for this disease.

PMID- 22964227
TI  - The XXIV International Complement Workshop (ICW) on October 10-15, 2012. Preface.

PMID- 22964229
TI  - Complement dysregulation and disease: from genes and proteins to diagnostics and
      drugs.
AB  - During the last decade, numerous studies have associated genetic variations in
      complement components and regulators with a number of chronic and infectious
      diseases. The functional characterization of these complement protein variants,
      in addition to recent structural advances in understanding of the assembly,
      activation and regulation of the AP C3 convertase, have provided important
      insights into the pathogenic mechanisms involved in some of these complement
      related disorders. This knowledge has identified potential targets for complement
      inhibitory therapies which are demonstrating efficacy and generating considerable
      expectation in changing the natural history of these diseases. Comprehensive
      understanding of the genetic and non-genetic risk factors contributing to these
      disorders will also result in targeting of the right patient groups in a
      stratified medicine approach through better diagnostics and individually tailored
      treatments, thereby improving management of patients.

PMID- 22964228
TI  - The complement system in ischemia-reperfusion injuries.
AB  - Tissue injury and inflammation following ischemia and reperfusion of various
      organs have been recognized for many years. Many reviews have been written over
      the last several decades outlining the role of complement in ischemia/reperfusion
      injury. This short review provides a current state of the art knowledge on the
      complement pathways activated, complement components involved and a review of the
      clinical biologics/inhibitors used in the clinical setting of
      ischemia/reperfusion. This is not a complete review of the complement system in
      ischemia and reperfusion injury but will give the reader an updated view point of
      the field, potential clinical use of complement inhibitors, and the future
      studies needed to advance the field.

PMID- 22964230
TI  - Bride and groom in systemic inflammation--the bells ring for complement and Toll
      in cooperation.
AB  - Attenuating the sepsis-induced systemic inflammatory response, with subsequent
      homeostatic imbalance, has for years been one of the main tasks in sepsis related
      research. Complement and the TLR family constitute two important upstream sensor
      and effector-systems of innate immunity. Although they act as partly independent
      branches of pattern recognition, recent evidence indicate a considerable cross
      talk implying that they can either compensate, synergize or antagonize each
      other. Combined inhibition of these pathways is therefore a particularly
      interesting approach with a profound anti-inflammatory potential. In previous
      preclinical studies, we demonstrated that targeting the key molecules C3 or C5 of
      complement and CD14 of the TLR family had a vast anti-inflammatory effect on Gram
      negative bacteria-induced inflammation and sepsis. In this review, we elucidate
      the significance of these key molecules as important targets for intervention in
      sepsis and systemic inflammatory response syndrome. Finally, we argue that a
      combined inhibition of complement and CD14 represent a potential general
      treatment regimen, beyond the limit of sepsis, including non-infectious systemic
      inflammation and ischemia reperfusion injury.

PMID- 22964232
TI  - The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune
      diseases.
AB  - Immunoglobulin G (IgG)-mediated activation of complement and IgG Fc receptors
      (FcgammaRs) are important defense mechanisms of the innate immune system to ward
      off infections. However, the same mechanisms can drive severe and harmful
      inflammation, when IgG antibodies react with self-antigens in solution or
      tissues, as described for several autoimmune diseases including systemic lupus
      erythematosus, rheumatoid arthritis, and immune vasculitis. More specifically,
      IgG immune complexes (ICs) can activate all three pathways of the complement
      system resulting in the generation of C3 and C5 cleavage products that can
      activate a panel of different complement receptors on innate and adaptive immune
      cells. Importantly, complement and FcgammaRs are often co-expressed on
      inflammatory immune cells such as neutrophils, monocytes, macrophages or
      dendritic cells and act in concert to mediate the inflammatory response in
      autoimmune diseases. In this context, the cross-talk between the receptor for the
      anaphylatoxin C5a, i.e. C5ar1 (CD88) and FcgammaRs is of major importance. Recent
      data suggest a model of bidirectional regulation, in which CD88 acts upstream of
      FcgammaRs and sets the threshold for FcgammaR-dependent effector responses by
      regulating the ratio between activating and inhibitory FcgammaRs. Vice versa,
      FcgammaR ligation can either amplify or block C5aR-mediated effector functions,
      depending on whether IgG IC aggregate activating or inhibitory FcgammaRs.
      Further, complement and FcgammaRs cooperate on B cells and on follicular
      dendritic cells to regulate the development of autoreactive B cells, their
      differentiation into plasma cells and, eventually, the production of
      autoantibodies. Here, we will give an update on recent findings regarding this
      complex regulatory network between complement and FcgammaRs, which may also
      regulate the inflammatory response in allergy, cancer and infection.

PMID- 22964233
TI  - Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological
      disorders.
AB  - The recent availability of eculizumab as the first complement inhibitor renewed
      the interest for complement-mediated damage in several human diseases. Paroxysmal
      nocturnal hemoglobinuria (PNH) may be considered the paradigm a disease caused by
      complement dysregulation specifically on erythrocytes; in fact, PNH is a clonal,
      non-malignant, hematological disorder characterized by the expansion of
      hematopoietic stem cells and progeny mature blood cells which are deficient in
      some surface proteins, including the two complement regulators CD55 and CD59. As
      a result, PNH erythrocytes are incapable to modulate on their surface physiologic
      complement activation, which eventually enables the terminal lytic complement
      leading to complement-mediated intravascular anemia - the typical clinical
      hallmark of PNH. In the last decade the anti-C5 monoclonal antibody has been
      proven effective for the treatment of PNH, resulting in a sustained control of
      complement-mediated intravascular hemolysis, with a remarkable clinical benefit.
      Since then, different diseases with a proved or suspected complement-mediated
      pathophysiology have been considered as candidate for a clinical complement
      inhibition. At the same time, the growing information on biological changes
      during eculizumab treatment in PNH have improved our understanding of different
      steps of the complement system in human diseases, as well as their modulation by
      current anti-complement treatment. As a result, investigators are currently
      working on novel strategy of complement inhibition, looking at the second
      generation of anti-complement agents which hopefully will be able to modulate
      distinct steps of the complement cascade. Here we review PNH as a disease model,
      focusing on the observation that led to the development of novel complement
      modulators; the discussion will be extended to other hemolytic disorders
      potentially candidate for clinical complement inhibition.

PMID- 22964231
TI  - Manipulating the mediator: modulation of the alternative complement pathway C3
      convertase in health, disease and therapy.
AB  - The complement network is increasingly recognized as an important triage system
      that is able to differentiate between healthy host cells, microbial intruders,
      cellular debris and immune complexes, and tailor its actions accordingly. At the
      center of this triage mechanism is the alternative pathway C3 convertase (C3bBb),
      a potent enzymatic protein complex capable of rapidly converting the inert yet
      abundant component C3 into powerful effector fragments (C3a and C3b), thereby
      amplifying the initial response on unprotected surfaces and inducing a variety of
      effector functions. A fascinating molecular mechanism of convertase assembly and
      intrinsic regulation, as well as the interplay with a panel of cell surface-bound
      and soluble inhibitors are essential for directing complement attack to intruders
      and protecting healthy host cells. While efficiently keeping immune surveillance
      and homeostasis on track, the reliance on an intricate cascade of interaction and
      conversion steps also renders the C3 convertase vulnerable to derail. On the one
      hand, tissue damage, accumulation of debris, or polymorphisms in complement genes
      may unfavorably shift the balance between activation and regulation, thereby
      contributing to a variety of clinical conditions. On the other hand, pathogens
      developed powerful evasion strategies to avoid complement attack by targeting the
      convertase. Finally, we increasingly challenge our bodies with foreign materials
      such as biomaterial implants or drug delivery vehicles that may induce adverse
      effects that are at least partially caused by complement activation and
      amplification via the alternative pathway. The involvement of the C3 convertase
      in a range of pathological conditions put this complex into the spotlight of
      complement-targeted drug discovery efforts. Fortunately, the physiological
      regulation and microbial evasion approaches provide a rich source of inspiration
      for the development of powerful treatment options. This review provides insight
      into the current knowledge about the molecular mechanisms that drive C3
      convertase activity, reveals common and divergent strategies of convertase
      inhibition employed by host and pathogens, and how this inhibitory arsenal can be
      tapped for developing therapeutic options to treat complement-related diseases.

PMID- 22964234
TI  - Interactions of the complement system with molecules of extracellular matrix:
      relevance for joint diseases.
AB  - Rheumatoid arthritis (RA) is a highly disabling disease affecting all structures
      of the joint. Understanding the pathology behind the development of RA is
      essential for developing targeted therapeutic strategies as well as for
      developing novel markers to predict disease onset. Several molecules normally
      hidden within the cartilage tissue are exposed to complement components in the
      synovial fluid upon cartilage breakdown. Some of these have been shown to
      activate complement and toll-like receptors, which may enhance an already
      existing inflammatory response, thereby worsening the course of disease. Other
      cartilage-resident molecules have in contrast shown to possess complement
      inhibitory properties. Knowledge about mechanisms behind pathological complement
      activation in the joints will hopefully lead to methods which allow us to
      distinguish patients with pathological complement activation from those where
      other inflammatory pathways are predominant. This will help to elucidate which
      patients will benefit from complement inhibitory therapies, which are thought to
      aid a specific subset of patients or patients at a certain stage of disease.
      Future challenges are to target the complement inhibition specifically to the
      joints to minimize systemic complement blockade.

PMID- 22964236
TI  - The tick-over theory revisited: is C3 a contact-activated protein?
AB  - The tick-over theory was first introduced in the 1970s to explain the presence of
      the initial C3b molecules, which are able to trigger complement activation by the
      alternative pathway in human plasma under physiological conditions. After the
      identification of the thioester, the predominant hypothesis has been that this
      bond is hydrolyzed at a slow but constant rate by nucleophilic attack by H(2)O,
      leading to the generation of C3(H(2)O). Here we put forward the hypothesis that
      the rate of hydrolysis of C3 to C3(H(2)O) may be greatly accelerated by the
      interaction between C3 and a number of biological and artificial interfaces,
      including gas bubbles, biomaterial surfaces and different lipid surfaces and
      complexes. We therefore propose that C3 should preferentially be regarded as a
      contact activated protein rather than a target for passive, random hydrolysis in
      the fluid phase.

PMID- 22964235
TI  - Targeted complement inhibition as a promising strategy for preventing
      inflammatory complications in hemodialysis.
AB  - Hemodialysis is the most common method used to remove waste and hazardous
      products of metabolism in patients suffering from renal failure. Hundreds of
      thousands of people with end-stage renal disease undergo hemodialysis treatment
      in the United States each year. Strikingly, the 5-year survival rate for all
      dialysis patients is only 35%. Most of the patients succumb to cardiovascular
      disease that is exacerbated by the chronic induction of inflammation caused by
      contact of the blood with the dialysis membrane. The complement system, a strong
      mediator of pro-inflammatory networks, is a key contributor to such biomaterial
      induced inflammation. Though only evaluated in experimental ex vivo settings,
      specific targeting of complement activation during hemodialysis has uncovered
      valuable information that points toward the therapeutic use of complement
      inhibitors as a means to control the unwelcomed inflammatory responses and
      consequent pathologies in hemodialysis patients.

PMID- 22964237
TI  - Complement and dysbiosis in periodontal disease.
AB  - Signaling crosstalk between complement and Toll-like receptors (TLRs) normally
      serves to coordinate host immunity. However, the periodontal bacterium
      Porphyromonas gingivalis expresses C5 convertase-like enzymatic activity and
      adeptly exploits complement-TLR crosstalk to subvert host defenses and escape
      elimination. Intriguingly, this defective immune surveillance leads to the
      remodeling of the periodontal microbiota to a dysbiotic state that causes
      inflammatory periodontitis. Understanding the mechanisms by which P. gingivalis
      modulates complement function to cause dysbiosis offers new targets for
      complement therapeutics.

PMID- 22964238
TI  - Putting the structure into complement.
AB  - In a field where structure has finally begun to have a real impact, a series of
      new structures over the last two years have further extended our understanding of
      some of the critical regulatory events of the complement system. Notably,
      information has begun to flow from larger assemblies of components which allow
      insight into the often transient assemblies critical to complement regulation at
      the cell surface. This review will summarise the key structures determined since
      the last International Complement Workshop and the insights these have given us,
      before highlighting some questions that still require molecular frameworks to
      drive understanding.

PMID- 22964239
TI  - Interactions of the humoral pattern recognition molecule PTX3 with the complement
      system.
AB  - The innate immune system comprises a cellular and a humoral arm. The long
      pentraxin PTX3 is a fluid phase pattern recognition molecule, which acts as an
      essential component of the humoral arm of innate immunity. PTX3 has antibody-like
      properties including interactions with complement components. PTX3 interacts with
      C1q, ficolin-1 and ficolin-2 as well as mannose-binding lectin, recognition
      molecules in the classical and lectin complement pathways. The formation of these
      heterocomplexes results in cooperative pathogen recognition and complement
      activation. Interactions with C4b binding protein and factor H, the principal
      regulators of the classical, lectin and alternative complement pathways, show
      that PTX3 also may have a major influence on the regulation of the complement
      system. The complex interaction of PTX3 with the complement system at different
      levels has broad implications for host defence and regulation of inflammation.

PMID- 22964240
TI  - Spectroscopic investigations of nano-sized titanium(IV) complexes containing
      electron-rich oxygen-based ligands.
AB  - A convenient method has been explored to synthesize some nano-sized, mixed-ligand
      complexes of titanium(IV) with the general formula [Ti(acac)Cl(2
      n)(L)(n)(OOCC(15)H(31))] (where Hacac=acetylacetone, HL=dibenzoylmethane or
      benzoylacetone and n=1 or 2). They have been synthesized by stepwise
      substitutions of chloride ions from titanium(IV) chloride with straight chain
      carboxylic acid and beta-diketones. These were characterized by elemental
      analyses, molecular weight determinations, spectral (electronic, FTIR, (1)H NMR
      and powder XRD) and TEM studies. Conductance measurements indicated their non
      conducting nature which may behave like insulators. Bidentate chelating nature of
      carboxylate and beta-diketones anions in the complexes was established by their
      infrared spectra. LMCT bands were observed in the electronic spectra. Molecular
      weight determinations indicated mononuclear nature of the complexes. Powder XRD
      and transmission electron microscopy (TEM) studies indicated the particles of
      these were lying in the nano-size range. The complexes exhibited high resistance
      to hydrolysis. On the basis of these studies, coordination number 7 or 8 is
      assigned for titanium in the synthesized complexes.

PMID- 22964241
TI  - Photophysics of indole, tryptophan and N-acetyl-L-tryptophanamide (NATA): heavy
      atom effect.
AB  - Previously reported flash photolysis studies showed that the triplet state
      lifetime of aqueous indoles is MUs long (12.5 MUs for tryptophan [10]), while
      other recently reported phosphorescence lifetimes of aqueous indoles, determined
      from photon counting phosphorescence techniques, vary from MUs (approximately 40
      MUs [11]) to ms (5 ms for indole [12]). This study was motivated to explain the
      discrepancy regarding the intrinsic triplet state lifetime of aqueous indole and
      its derivatives: tryptophan and N-acetyl-L-tryptophanamide (NATA). For this
      purpose, a new methodology based on both fluorescence and phosphorescence decay
      kinetics incorporating the heavy atom effect have been applied in order to
      determine some quantitative parameters of the photophysics of indole and its
      derivatives. Additionally, we have also determined the triplet state lifetimes of
      the studied indoles using flash photolysis in which contributions from both a
      first order component and a second order component (from triplet-triplet
      annihilation) have been taken into account in the triplet state depopulation. The
      measured phosphorescence lifetime of the indoles examined measures between the
      values reported by Fischer and Strambini and is consistent with the triplet state
      lifetime determined from flash photolysis. We hope that the results obtained in
      this paper would be helpful for deriving structural and dynamical information
      from phosphorescence data of tryptophan residues in proteins.

PMID- 22964242
TI  - Dye-sensitized solar cells and complexes between pyridines and iodines. A NMR, IR
      and DFT study.
AB  - Interactions between triiodide (I(3)(-)) and 4-tert-butylpyridine (4TBP) as
      postulated in dye-sensitized solar cells (DSC) are investigated by means of (13)C
      NMR and IR spectroscopy supported by DFT calculations. The charge transfer (CT)
      complex 4TBP.I(2) and potential salts such as (4TBP)(2)I(+), I(3)(-) were
      synthesized and characterized by IR and (13)C NMR spectroscopy. However, mixing
      (butyl)(4)N(+), I(3)(-) and 4TBP at concentrations comparable to those of the DSC
      solar cell did not lead to any reaction. Neither CT complexes nor cationic
      species like (4TBP)(2)I(+) were observed, judging from the (13)C NMR
      spectroscopic evidence. This questions the previously proposed formation of
      (4TBP)(2)I(+) in DSC cells.

PMID- 22964243
TI  - Structural, vibrational and DSC investigations of the bis-4-benzyl piperidinium
      tetraoxoselenate monohydrate crystal.
AB  - A new organic-inorganic salt, bis-4-benzyl piperidinium tetraoxoselenate
      monohydrate has been synthesized and characterized by X-ray diffraction, FT-IR
      and FT-Raman spectroscopies. The title compound crystallizes in the monoclinic
      system P2(1)/c at room temperature with the following parameters: a=8.617(3)A,
      b=27.140(9)A, c=10.926(5)A, beta=96.46(4) degrees  and Z=4. Its vibrational
      spectra have been discussed on the basis on quantum chemical density theory (DFT)
      calculation using B3LYP/6-31G(*) approach. The role of the intermolecular
      interaction in this crystal is analyzed. Acidic protons of the selenate group
      were transferred to the organic cation giving the singly-protonated cation. The
      ability of ions to form spontaneous three-dimensional structure through O-H...O
      and N-H...O hydrogen bond is fully utilized. These hydrogen bonds give notable
      vibrational effects.

PMID- 22964244
TI  - Vibrational and electronic spectra of [Cu(L-ornithinato)2Cl2].2H2O.
AB  - The FTIR and FT-Raman spectra of a Cu(II) complex of ornithine of composition
      [Cu(L-ornithinato)(2)Cl(2)].2H(2)O were recorded and analyzed in relation to its
      structural peculiarities and by comparison with the spectra of ornithine
      hydrochloride and of other bis(amino acid) complexes of Cu(II). The electronic
      spectrum of the complex is also briefly discussed.

PMID- 22964245
TI  - Safety and pharmacokinetics of intravaginal rings delivering tenofovir in pig
      tailed macaques.
AB  - Antiretroviral-based microbicides applied topically to the vagina may play an
      important role in protecting women from HIV infection. Incorporation of the
      nucleoside reverse transcriptase inhibitor tenofovir (TFV) into intravaginal
      rings (IVRs) for sustained mucosal delivery may lead to increased microbicide
      product adherence and efficacy compared with those of conventional vaginal
      formulations. Formulations of a novel "pod IVR" platform spanning a range of IVR
      drug loadings and daily release rates of TFV were evaluated in a pig-tailed
      macaque model. The rings were safe and exhibited sustained release at controlled
      rates over 28 days. Vaginal secretion TFV levels were independent of IVR drug
      loading and were able to be varied over 1.5 log units by changing the ring
      configuration. Mean TFV levels in vaginal secretions were 72.4 +/- 109 MUg ml(-1)
      (slow releasing) and 1.84 +/- 1.97 mg ml(-1) (fast releasing). The mean TFV
      vaginal tissue concentration from the slow-releasing IVRs was 76.4 +/- 54.8 MUg
      g(-1) and remained at steady state 7 days after IVR removal, consistent with the
      long intracellular half-life of TFV. Intracellular tenofovir diphosphate (TFV
      DP), the active moiety in defining efficacy, was measured in vaginal lymphocytes
      collected in the study using the fast-releasing IVR formulation. Mean
      intracellular TFV-DP levels of 446 +/- 150 fmol/10(6) cells fall within a range
      that may be protective of simian-human immunodeficiency virus strain SF162p3
      (SHIV(SF162p3)) infection in nonhuman primates. These data suggest that TFV
      releasing IVRs based on the pod design have potential for the prevention of
      transmission of human immunodeficiency virus type 1 (HIV-1) and merit further
      clinical investigation.

PMID- 22964246
TI  - In vitro antifungal activity of isavuconazole against Madurella mycetomatis.
AB  - Currently, therapy of black-grain mycetoma caused by Madurella mycetomatis
      consists of extensive debridement of the infected tissue combined with prolonged
      antifungal therapy with ketoconazole or itraconazole. In the present study, the
      in vitro activity of the new triazole isavuconazole toward M. mycetomatis was
      evaluated. Isavuconazole appeared to have high activity against M. mycetomatis,
      with MICs ranging from <=0.016 to 0.125 MUg/ml. Due to its favorable
      pharmacokinetics, isavuconazole could be a promising antifungal agent in the
      treatment of mycetoma.

PMID- 22964247
TI  - KPC-9, a novel carbapenemase from clinical specimens in Israel.
AB  - A bla(KPC-9) carbapenemase variant was discovered in isolates of Klebsiella
      pneumoniae and Escherichia coli from a single patient. It differed from bla(KPC
      3) by one amino acid substitution (Val239Ala). The K. pneumoniae isolate was
      typed as ST258, as was the epidemic Israeli KPC-3 clone. bla(KPC-9) was found on
      a plasmid indistinguishable from pKpQIL that carries bla(KPC-3) in the epidemic
      clone. Compared to KPC-3, KPC-9 conferred less resistance to carbapenems and
      higher resistance to ceftazidime.

PMID- 22964248
TI  - Inhibition of Staphylococcus epidermidis biofilm by trimethylsilane plasma
      coating.
AB  - Biofilm formation on implantable medical devices is a major impediment to the
      treatment of nosocomial infections and promotes local progressive tissue
      destruction. Staphylococcus epidermidis infections are the leading cause of
      biofilm formation on indwelling devices. Bacteria in biofilms are highly
      resistant to antibiotic treatment, which in combination with the increasing
      prevalence of antibiotic resistance among human pathogens further complicates
      treatment of biofilm-related device infections. We have developed a novel plasma
      coating technology. Trimethylsilane (TMS) was used as a monomer to coat the
      surfaces of 316L stainless steel and grade 5 titanium alloy, which are widely
      used in implantable medical devices. The results of biofilm assays demonstrated
      that this TMS coating markedly decreased S. epidermidis biofilm formation by
      inhibiting the attachment of bacterial cells to the TMS-coated surfaces during
      the early phase of biofilm development. We also discovered that bacterial cells
      on the TMS-coated surfaces were more susceptible to antibiotic treatment than
      their counterparts in biofilms on uncoated surfaces. These findings suggested
      that TMS coating could result in a surface that is resistant to biofilm
      development and also in a bacterial community that is more sensitive to
      antibiotic therapy than typical biofilms.

PMID- 22964250
TI  - A first-in-human, randomized, double-blind, placebo-controlled, single- and
      multiple-ascending oral dose study to assess the safety and tolerability of
      LFF571 in healthy volunteers.
AB  - Clostridium difficile is the leading cause of hospital-acquired infectious
      diarrhea. LFF571 is a novel inhibitor of the prokaryotic translation elongation
      factor Tu and is active against a range of bacterial species, including C.
      difficile. This first-in-human study investigated the safety and pharmacokinetics
      of single and multiple ascending oral doses of LFF571 in healthy subjects. This
      was a randomized, double-blind, placebo-controlled study. Except for one cohort,
      LFF571 was given with a high-fat meal to all single-dose cohorts (25 mg, 100 mg,
      400 mg, and 1,000 mg). In the multiple-dose cohorts (25 mg, 100 mg, or 200 mg
      every 6 h for 10 days), LFF571 was given without regard to food. A total of 56
      subjects completed the study, with 32 and 25 receiving single and multiple doses,
      respectively. There were no deaths, no serious adverse events, and no subject
      withdrawals due to an adverse event. The most common adverse event was diarrhea;
      gastrointestinal pain or distension was also noted. Diarrhea did not develop more
      frequently among subjects who received LFF571 than among those who received a
      placebo. LFF571 had limited systemic exposure and high steady-state fecal
      concentrations. The highest concentration of LFF571 in serum (3.2 ng/ml) was
      observed after the last dose in a subject who received 200 mg every 6 h for 10
      days. LFF571 was generally safe and well tolerated in single and multiple oral
      doses in healthy subjects. The minimal serum and high fecal concentrations
      support the further development of LFF571 for the treatment of C. difficile
      infections.

PMID- 22964249
TI  - In vitro and in vivo antimicrobial activities of gallium nitrate against
      multidrug-resistant Acinetobacter baumannii.
AB  - Multidrug-resistant Acinetobacter baumannii poses a tremendous challenge to
      traditional antibiotic therapy. Due to the crucial role of iron in bacterial
      physiology and pathogenicity, we investigated iron metabolism as a possible
      target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due
      to chemical similarity, gallium competes with iron for binding to several redox
      enzymes, thereby interfering with a number of essential biological reactions. We
      found that Ga(NO(3))(3), the active component of an FDA-approved drug (Ganite),
      inhibits the growth of a collection of 58 A. baumannii strains in both chemically
      defined medium and human serum, at concentrations ranging from 2 to 80 MUM and
      from 4 to 64 MUM, respectively. Ga(NO(3))(3) delayed the entry of A. baumannii
      into the exponential phase and drastically reduced bacterial growth rates.
      Ga(NO(3))(3) activity was strongly dependent on iron availability in the culture
      medium, though the mechanism of growth inhibition was independent of
      dysregulation of gene expression controlled by the ferric uptake regulator Fur.
      Ga(NO(3))(3) also protected Galleria mellonella larvae from lethal A. baumannii
      infection, with survival rates of >=75%. At therapeutic concentrations for humans
      (28 MUM plasma levels), Ga(NO(3))(3) inhibited the growth in human serum of 76%
      of the multidrug-resistant A. baumannii isolates tested by >=90%, raising
      expectations on the therapeutic potential of gallium for the treatment of A.
      baumannii bloodstream infections. Ga(NO(3))(3) also showed strong synergism with
      colistin, suggesting that a colistin-gallium combination holds promise as a last
      resort therapy for infections caused by pan-resistant A. baumannii.

PMID- 22964251
TI  - Pseudomonas aeruginosa syntrophy in chronically colonized airways of cystic
      fibrosis patients.
AB  - Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients undergo
      remarkable phenotypic divergence over time, including loss of pigmentation,
      hemolysis, motility, and quorum sensing and emergence of antibiotic
      hypersusceptibility and/or auxotrophism. With prolonged antibiotic treatment and
      steady decline in lung function in chronically infected patients, the divergent
      characteristics associated with CF isolates have traditionally been regarded as
      "adapted/unusual virulence," despite the degenerative nature of these
      adaptations. We examined the phenotypic and genotypic diversity in clonally
      related isogenic strains of P. aeruginosa from individual CF patients. Our
      observations support a novel model of intra-airway pseudomonal syntrophy and
      accompanying loss of virulence. A 2007 calendar year collection of CF P.
      aeruginosa isolates (n = 525) from 103 CF patients yielded in vitro MICs of
      sulfamethoxazole-trimethoprim (SMX-TMP, which typically has no activity against
      P. aeruginosa) ranging from 0.02 to >32 MUg/ml (median, 1.5). Coisolation of
      clonally related SMX-TMP-susceptible and -resistant P. aeruginosa strains from
      the same host was common (57%), as were isogenic coisolates with mutations in
      efflux gene determinants (mexR, mexAB-oprM, and mexZ) and genes governing DNA
      mismatch repair (mutL and mutS). In this cohort, complete in vitro growth
      complementation between auxotrophic and prototrophic P. aeruginosa isogenic
      strains was evident and concurrent with the coding sequence mosaicism in
      resistance determinants. These observations suggest that syntrophic clonal
      strains evolve in situ in an organized colonial structure. We propose that P.
      aeruginosa adopts a multicellular lifestyle in CF patients due to host selection
      of an energetically favorable, less-virulent microbe restricted within and
      symbiotic with the airway over the host's lifetime.

PMID- 22964252
TI  - Chitin synthases with a myosin motor-like domain control the resistance of
      Aspergillus fumigatus to echinocandins.
AB  - Aspergillus fumigatus has two chitin synthases (CSMA and CSMB) with a myosin
      motor-like domain (MMD) arranged in a head-to-head configuration. To understand
      the function of these chitin synthases, single and double csm mutant strains were
      constructed and analyzed. Although there was a slight reduction in mycelial
      growth of the mutants, the total chitin synthase activity and the cell wall
      chitin content were similar in the mycelium of all of the mutants and the
      parental strain. In the conidia, chitin content in the DeltacsmA strain cell wall
      was less than half the amount found in the parental strain. In contrast, the
      DeltacsmB mutant strain and, unexpectedly, the DeltacsmA/DeltacsmB mutant strain
      did not show any modification of chitin content in their conidial cell walls. In
      contrast to the hydrophobic conidia of the parental strain, conidia of all of the
      csm mutants were hydrophilic due to the presence of an amorphous material
      covering the hydrophobic surface-rodlet layer. The deletion of CSM genes also
      resulted in an increased susceptibility of resting and germinating conidia to
      echinocandins. These results show that the deletion of the CSMA and CSMB genes
      induced a significant disorganization of the cell wall structure, even though
      they contribute only weakly to the overall cell wall chitin synthesis.

PMID- 22964253
TI  - Comparison of the in vivo pharmacokinetics and in vitro dissolution of
      raltegravir in HIV patients receiving the drug by swallowing or by chewing.
AB  - The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by
      high interpatient/intrapatient variability. We investigated the potential
      contribution of the drug pharmaceutical formulation to RAL pharmacokinetics. We
      first compared in vivo the pharmacokinetics of RAL for 67 patients to whom the
      drug was administered by swallowing the intact tablet with those obtained from 13
      HIV-infected patients who chewed the RAL tablet due to swallowing difficulties.
      Subsequently, we evaluated in vitro the dissolution of RAL tablets under
      different conditions. In the in vivo study, we found that patients given RAL by
      chewing the tablets presented pharmacokinetic profiles characterized by
      significantly higher RAL absorption than did patients receiving the drug by
      swallowing. The in vitro studies showed that when the whole tablets were exposed
      to an acidic medium, the release of RAL was very low, whereas when the tablets
      were crushed, the profiles presented significantly higher concentrations of RAL.
      Crushed tablets tested in water or in a pH 6.8 buffer exhibited prompt and
      complete dissolution of RAL. HIV-infected patients receiving RAL by chewing the
      tablet showed higher drug absorption and reduced pharmacokinetic variability
      compared with patients swallowing the intact tablet. This is related to problems
      in tablet disintegration and to erratic drug absorption. The amelioration of the
      RAL pharmaceutical formulation could improve drug pharmacokinetics.

PMID- 22964255
TI  - Combination therapy with ampicillin and daptomycin for treatment of Enterococcus
      faecalis endocarditis.

PMID- 22964254
TI  - Comparative pharmacodynamics of the new oxazolidinone tedizolid phosphate and
      linezolid in a neutropenic murine Staphylococcus aureus pneumonia model.
AB  - Tedizolid phosphate (TR-701) is a novel oxazolidinone prodrug (converted to the
      active form tedizolid [TR-700]) with potent Staphylococcus aureus activity. The
      current studies characterized and compared the in vivo
      pharmacokinetic/pharmacodynamic (PD) characteristics of TR-701/TR-700 and
      linezolid against methicillin-susceptible S. aureus (MSSA) and methicillin
      resistant S. aureus (MRSA) in the neutropenic murine pneumonia model. The
      pharmacokinetic properties of both drugs were linear over a dose range of 0.625
      to 40 mg/kg of body weight. Protein binding was 30% for linezolid and 85% for TR
      700. Mice were infected with one of 11 isolates of S. aureus, including MSSA and
      community- and hospital-acquired MRSA strains. Each drug was administered by oral
      gastric gavage every 12 h (q12h). The dosing regimens ranged from 1.25 to 80
      mg/kg/12 h for linezolid and 0.625 to 160 mg/kg/12 h for TR-701. At the start of
      therapy, mice had 6.24 +/- 0.40 log(10) CFU/lungs, which increased to 7.92 +/-
      1.02 log(10) CFU/lungs in untreated animals over a 24-h period. A sigmoid maximum
      effect (E(max)) model was used to determine the antimicrobial exposure associated
      with net stasis (static dose [SD]) and 1-log-unit reduction in organism relative
      to the burden at the start of therapy. The static dose pharmacodynamic targets
      for linezolid and TR-700 were nearly identical, at a free drug (non-protein
      bound) area under the concentration-time curve over 24 h in the steady state
      divided by the MIC (AUC/MIC ratio) of 19 and 20, respectively. The 1-log-unit
      kill endpoints were also similar, at 46.1 for linezolid and 34.6 for TR-700. The
      exposure targets were also comparable for both MSSA and MRSA isolates. These
      dosing goals support further clinical trial examination of TR-701 in MSSA and
      MRSA pneumonia.

PMID- 22964256
TI  - Cell envelope stress response in cell wall-deficient L-forms of Bacillus
      subtilis.
AB  - L-forms are cell wall-deficient bacteria that can grow and proliferate in
      osmotically stabilizing media. Recently, a strain of the Gram-positive model
      bacterium Bacillus subtilis was constructed that allowed controlled switching
      between rod-shaped wild-type cells and corresponding L-forms. Both states can be
      stably maintained under suitable culture conditions. Because of the absence of a
      cell wall, L-forms are known to be insensitive to beta-lactam antibiotics, but
      reports on the susceptibility of L-forms to other antibiotics that interfere with
      membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and
      strongly influenced by strain background and method of L-form generation. Here we
      investigated the response of B. subtilis to the presence of cell envelope
      antibiotics, with regard to both antibiotic resistance and the induction of the
      known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results
      show that B. subtilis L-forms are resistant to antibiotics that interfere with
      the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are
      hypersensitive to nisin and daptomycin, which both affect membrane integrity.
      Moreover, we established a lacZ-based reporter gene assay for L-forms and provide
      evidence that LiaRS senses its inducers indirectly (damage sensing), while the
      Bce module detects its inducers directly (drug sensing).

PMID- 22964257
TI  - Novel method to assess antiretroviral target trough concentrations using in vitro
      susceptibility data.
AB  - Durable suppression of HIV-1 replication requires the establishment of
      antiretroviral drug concentrations that exceed the susceptibility of the virus
      strain(s) infecting the patient. Minimum plasma drug concentrations (C(trough))
      are correlated with response, but determination of target C(trough) values is
      hindered by a paucity of in vivo concentration-response data. In the absence of
      these data, in vitro susceptibility measurements, adjusted for serum protein
      binding, can provide estimations of suppressive in vivo drug concentrations. We
      derived serum protein binding correction factors (PBCF) for protease inhibitors,
      nonnucleoside reverse transcriptase inhibitors, and an integrase inhibitor by
      measuring the effect of a range of human serum concentrations on in vitro drug
      susceptibility measured with the PhenoSense HIV assay. PBCFs corresponding to
      100% HS were extrapolated using linear regression and ranged from 1.4 for
      nevirapine to 77 for nelfinavir. Using the mean 95% inhibitory concentration
      (IC(95)) for >=1,200 drug-susceptible viruses, we calculated protein-bound IC(95)
      (PBIC(95)) values. PBIC(95) values were concordant with the minimum effective
      C(trough) values that were established in well-designed pharmacodynamic studies
      (e.g., indinavir, saquinavir, and amprenavir). In other cases, the PBIC(95)
      values were notably lower (e.g., darunavir, efavirenz, and nevirapine) or higher
      (nelfinavir and etravirine) than existing target recommendations. The
      establishment of PBIC(95) values as described here provides a convenient and
      standardized approach for estimation of the minimum drug exposure that is
      required to maintain viral suppression and prevent the emergence of drug
      resistant variants, particularly when in vivo concentration-response
      relationships are lacking.

PMID- 22964259
TI  - Evaluation of a new approach to the treatment of lymphedema resulting from breast
      cancer therapy.
AB  - PURPOSE: The aim of this study was to evaluate a new form of intensive treatment
      for arm lymphedema. METHODS: A prospective study of 66 patients with breast
      cancer-related lymphedema was performed. The ages of the patients ranged from 35
      to 83 years old with a mean of 58.8 years. Diagnosis of lymphedema was made by
      physical examination and water-displacement volumetry (a difference of >= 200 mL
      between arms). All the patients were submitted to clinical treatment in an
      outpatient setting which involved a once-weekly session of 3 to 4h of manual and
      mechanical lymph drainage, myolymphokinetic activities and exercising using
      facilitating apparatuses and the use of a medical compression sleeve. Monthly
      volumetry evaluations were routinely performed. The Student t-test was employed
      for statistical analysis with an alpha level of 5% (p<0.05) being considered
      significant. RESULTS: The mean follow-up time between cancer treatment and this
      study was 12.3 months. A significant reduction in the size of the arms was
      observed for all patients. The mean difference between the lymphedematous and
      normal arms of all patients was 553.8 mL at the start of treatment and a mean
      reduction of 70.1% (388.7 mL) of the edema was achieved (p=0.0001). CONCLUSION:
      In our experience, this model of treatment appeared efficacious in decreasing and
      maintaining the reduction in volume of arm in breast cancer-related lymphedema.

PMID- 22964260
TI  - Aspiration pneumonia in old patients with dementia. Prognostic factors of
      mortality.
AB  - BACKGROUND: Prognostic factors of mortality in elderly patients with dementia
      with aspiration pneumonia (AP) are scarcely known. We determined the mortality
      rate and prognostic factors in old patients with dementia hospitalized due to AP.
      METHODS: We prospectively studied 120 consecutive patients aged >= 75 years with
      dementia admitted with AP to two tertiary university hospitals. We collected data
      on demographic and clinical variables and comorbidities. Oropharyngeal swallowing
      was assessed by the water swallow test. RESULTS: Sixty-one (50.8%) patients were
      female, and mean age was 86 +/- 9 years. The swallow test was performed in 68
      patients, revealing aspiration in 92.6%. Patients with repeat AP (28.3%) were
      more-frequently taking thickeners (61.8% vs.11.6%, p<0.0001) and were less
      frequently prescribed angiotensin-converting-enzyme (ACE) inhibitors (8.8% vs.
      27.9%, p<0.001) than patients with a first episode. Hospital mortality was 33.3%;
      these patients had lower lymphocyte counts and higher percentage of multilobar
      involvement. In the multivariate model, involvement of >= 2 pulmonary lobes was
      associated with hospital mortality (OR 3.051, 95% CI 1.248 to 7.458, p<0.01). Six
      month mortality was 50.8%; these patients were older and had worse functional
      capacity and laboratory data indicative of malnutrition. In the multivariate
      model, lower albumin levels were associated with six-month mortality (OR 1.129,
      95% CI 1.008 to 1.265, p<0.03). CONCLUSION: In-hospital and 6-month mortality
      were high (one-third and one-half patients, respectively). Multilobar involvement
      and lower lymphocyte counts were associated with hospital mortality, and older
      age, greater dependence and malnutrition with six-month mortality.

PMID- 22964258
TI  - Overview of potential procedural and participant-related confounds for
      neuroimaging of the resting state.
AB  - Studies of intrinsic brain activity in the resting state have become increasingly
      common. A productive discussion of what analysis methods are appropriate, of the
      importance of physiologic correction and of the potential interpretations of
      results has been ongoing. However, less attention has been paid to factors other
      than physiologic noise that may confound resting-state experiments. These range
      from straightforward factors, such as ensuring that participants are all
      instructed in the same manner, to more obscure participant-related factors, such
      as body weight. We provide an overview of such potentially confounding factors,
      along with some suggested approaches for minimizing their impact. A particular
      theme that emerges from the overview is the range of systematic differences
      between types of study groups (e.g., between patients and controls) that may
      influence resting-state study results.

PMID- 22964261
TI  - Ultrafast dynamics of dithienylethenes differently linked to the surface of TiO2
      nanoparticles.
AB  - The photoinduced dynamics of a dithienylethene chromophore coupled to the surface
      of TiO(2) by either a tripodal linker or a carboxyl group was investigated with
      ultrafast transient absorption spectroscopy. The absence of electron transfer
      from the photoexcited tripodal dithienylethene chromophore demonstrates that the
      tripod efficiently uncouples the electronic systems of dithienylethene and
      TiO(2). Contrary to this situation, photoinduced electron transfer can compete
      with ultrafast intramolecular relaxation in the COOH-dithienylethene/TiO(2)
      coupled system. An electron transfer rate of 1.1 * 10(12) s(-1) can be extracted,
      which is considerably slower than the intramolecular relaxation rate of the
      dithienylethene (3.7 * 10(12) s(-1)). Consequently, the electron transfer
      reaction exhibits a low efficiency.

PMID- 22964262
TI  - Breast reconstruction with autologous fat graft mixed with platelet-rich plasma.
AB  - BACKGROUND: The purpose of this study was to review the authors' experience of
      fat grafting, evaluating the effects related to the use of fat grafting with
      platelet-rich plasma (PRP) in the improvement of fat volume in breast
      reconstruction and comparing the results with a control group (only centrifuged
      fat grafting). METHODS: A total of 50 patients aged between 19 and 60 years
      affected by breast soft-tissue defects were analyzed at the Plastic and
      Reconstructive Department of the University of Tor Vergata. They were treated
      with fat grafting + PRP. The control group (50 patients with breast soft-tissue
      defects) were treated with centrifuged fat grafting injection according to
      Coleman's procedure. RESULTS: The patients treated with PRP added to the
      autologous fat grafts showed a 69% maintenance of the contour restoring and of 3
      dimensional volume after 1 year, whereas the patients of the control group
      treated with centrifuged fat grafting showed a 39% maintenance. CONCLUSION: PRP
      mixed with fat grafting leads to an improvement in maintaining breast volume in
      patients affected by breast soft-tissue defects.

PMID- 22964263
TI  - Intradetrusor injection of botulinum toxin for the management of refractory
      overactive bladder syndrome: an update.
AB  - Overactive bladder (OAB) is a common syndrome that has a negative impact on daily
      activities and quality of life. The first-line treatment to manage this condition
      includes behavioral modifications, physical treatment, and oral pharmacotherapy
      with antimuscarinics. Botulinum toxin has emerged as an alternative and second
      line treatment option for patients with OAB who are refractory to first-line
      treatment modalities when injected into the detrusor muscle. Although its
      application in the management of OAB remains off label, studies have shown its
      efficacy both subjectively and objectively. It is considered as a minimally
      invasive and reversible alternative. Adequate dosage of the toxin, number of
      injection sites, and reinjection rates are yet to be determined. This review
      attempts to provide an update on the current position of botulinum toxin in
      managing refractory OAB addressing contemporary data on the mechanism of action,
      technique, safety, complications, and clinical results.

PMID- 22964264
TI  - Laparoendoscopic single-site surgery for partial nephrectomy without ischemia
      using a microwave tissue coagulator.
AB  - BACKGROUND: Herein, we report our initial experience with laparoendoscopic single
      site surgery for partial nephrectomy (LESSPN) using a microwave tissue coagulator
      (MTC). METHODS: Two patients with small and exophytic renal tumors underwent
      LESSPN. A multichannel port was inserted into the peritoneal or retroperitoneal
      space through a 3-cm skin incision. After tumor exposure, the surgeon introduced
      a laparoscopic MTC instrument through a 5-mm port and the tumor margin was
      coagulated circumferentially. After coagulation, the tumor was resected without
      renal pedicle clamping. RESULTS: These procedures were successfully performed
      without any conversions to standard laparoscopy or need for placement of
      additional trocars. The operative times were 183 and 160 minutes, respectively.
      The estimated blood loss was <150 mL in both cases. The final length of the LESS
      wound was 3 cm. Using the transumbilical approach, the operative scar receded
      into the umbilicus and was hardly visible. CONCLUSIONS: This novel surgical
      technique is feasible and enables the bloodless resection of a renal tumor
      without renal pedicle clamping. Further clinical experience and longer follow-up
      are needed to define the benefits of this new technique.

PMID- 22964265
TI  - Influence of preoperative anxiety on hypotension after spinal anaesthesia in
      women undergoing Caesarean delivery.
AB  - BACKGROUND: We designed a prospective observational study to assess the effect of
      preoperative anxiety on hypotension after spinal anaesthesia. METHODS: After IRB
      approval and signed informed consent, 100 healthy term parturients undergoing
      elective Caesarean delivery under spinal anaesthesia were enrolled. Direct
      psychological assessments of preoperative anxiety were verbal analogue scale
      (VAS) (0-10) anxiety score and State-Trait Anxiety Inventory questionnaire (STAI
      s); salivary amylase was measured as an indirect physical assessment of anxiety.
      Direct and indirect anxiety data were transformed into ordinal groups for low,
      medium, and high anxiety (VAS: low 0-3, medium 4-6, high 7-10; STAI-s: low <40,
      medium 40-55, high >55; log(10) salivary amylase: low <3, medium 3-4, high >4).
      Spinal anaesthesia was performed using hyperbaric bupivacaine 10 mg and fentanyl
      20 MUg. All patients received i.v. crystalloid 500 ml prehydration and 500 ml
      cohydration. Hypotension was treated by standardized protocol (fluid bolus and
      ephedrine or phenylephrine depending on maternal heart rate). Systolic arterial
      pressure (SAP) was measured at baseline and every minute after spinal
      anaesthesia. The effect of low, medium, and high anxiety groups on the maximum
      percentage change in SAP (%DeltaSAP) was assessed (one-way analysis of variance,
      Tukey's honestly significant difference). RESULTS: Ninety-three patients were
      included in analysis. There was a significant effect of direct psychological
      measures of anxiety on %DeltaSAP (VAS P=0.004; STAI-s P=0.048). There was a
      significant difference between low and high anxiety groups (VAS P=0.003; STAI-s
      P=0.038), but not between other anxiety groups. Salivary amylase did not
      correlate with %DeltaSAP. CONCLUSIONS: Preoperative anxiety assessed by VAS had a
      significant effect on hypotension after spinal anaesthesia.

PMID- 22964266
TI  - Mindfulness-based therapy in adults with an autism spectrum disorder: a
      randomized controlled trial.
AB  - Research shows that depression and anxiety disorders are the most common
      psychiatric concern in autism spectrum disorders (ASD). Mindfulness-based therapy
      (MBT) has been found effective in reducing anxiety and depression symptoms,
      however research in autism is limited. Therefore, we examined the effects of a
      modified MBT protocol (MBT-AS) in high-functioning adults with ASD. 42
      participants were randomized into a 9-week MBT-AS training or a wait-list control
      group. Results showed a significant reduction in depression, anxiety and
      rumination in the intervention group, as opposed to the control group.
      Furthermore, positive affect increased in the intervention group, but not in the
      control group. Concluding, the present study is the first controlled trial to
      demonstrate that adults with ASD can benefit from MBT-AS.

PMID- 22964267
TI  - Intra-articular hip injections using ultrasound guidance: accuracy using a linear
      array transducer.
AB  - OBJECTIVE: To describe the accuracy of sonographically guided intra-articular hip
      injections with a linear array transducer. DESIGN: Retrospective review. SETTING:
      Private outpatient clinic. METHODS: A single experienced operator performed 11
      ultrasound-guided intra-articular hip injections by using a linear array
      transducer. Intra-articular placement was confirmed with contrast agent and
      fluoroscopy. MAIN OUTCOME MEASUREMENTS: Assessment of injected contrast within
      the hip joint via fluoroscopic imaging. RESULTS: All 11 sonographically guided
      hip injections were accurately placed within the hip joint by the use of a linear
      array transducer (100% accuracy). CONCLUSION: This retrospective review suggests
      that physicians who use a linear array transducer can accurately perform intra
      articular hip injections in an outpatient setting.

PMID- 22964269
TI  - Age-related differences in hepatic ischemia/reperfusion: gene activation, liver
      injury, and protective effect of melatonin.

PMID- 22964268
TI  - Perturbations in the gene regulatory pathways controlling mitochondrial energy
      production in the failing heart.
AB  - The heart is an omnivore organ that requires constant energy production to match
      its functional demands. In the adult heart, adenosine-5'-triphosphate (ATP)
      production occurs mainly through mitochondrial fatty acid and glucose oxidation.
      The heart must constantly adapt its energy production in response to changes in
      substrate supply and work demands across diverse physiologic and pathophysiologic
      conditions. The cardiac myocyte maintains a high level of mitochondrial ATP
      production through a complex transcriptional regulatory network that is
      orchestrated by the members of the peroxisome proliferator-activated receptor
      gamma coactivator-1 (PGC-1) family. There is increasing evidence that during the
      development of cardiac hypertrophy and in the failing heart, the activity of this
      network, including PGC-1, is altered. This review summarizes our current
      understanding of the perturbations in the gene regulatory pathways that occur
      during the development of heart failure. An appreciation of the role this
      regulatory circuitry serves in the regulation of cardiac energy metabolism may
      unveil novel therapeutic targets aimed at the metabolic disturbances that presage
      heart failure. This article is part of a Special Issue entitled:Cardiomyocyte
      Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

PMID- 22964270
TI  - Resuscitative effect of centhaquin after hemorrhagic shock in rats.
AB  - BACKGROUND: Centhaquin is a cardiovascular active agent that significantly
      reduced blood lactate levels and enhanced resuscitative effect of hypertonic
      saline. The present study was carried out to determine the resuscitative effect
      of centhaquin and compare that with large-volume lactated Ringer (LR) solution in
      hemorrhaged rats. MATERIALS AND METHODS: Male, adult Sprague-Dawley rats were
      anesthetized with urethane, and a pressure catheter SPR-320 was placed in the
      left femoral artery; another pressure-volume catheter SPR-869 was placed into the
      left ventricle through carotid artery. Hemorrhage was induced by withdrawing
      blood from the right femoral artery, and the mean arterial pressure (MAP) was
      maintained at 35 mm Hg for 30 minutes after which resuscitation was performed
      using LR solution (LR-100) (100% shed blood volume), centhaquin (0.017, 0.05, and
      0.15 mg/kg) dissolved in LR (100% shed blood volume), or LR-300 (300% shed blood
      volume). Arterial blood gases and cardiovascular parameters were determined
      before the induction of hemorrhage and at various times after hemorrhage.
      RESULTS: It was found that survival time after resuscitation with LR-100 was 78
      +/- 10 min. Centhaquin in doses of 0.017 and 0.05 mg/kg significantly improved
      survival time to 291 +/- 57 and 387 +/- 39 min, respectively. Blood lactate
      levels (millimoles per liter) increased from 7.22 +/- 0.67 at hemorrhage to 10.20
      +/- 0.61 at 60 min after resuscitation with LR-100. On the other hand, blood
      lactate levels significantly decreased to 3.55 +/- 0.07 and 4.08 +/- 0.28 at 60
      min after resuscitation with 0.017 and 0.05 mg/kg doses of centhaquin,
      respectively. Centhaquin in these doses produced a 55% and 59% increase in MAP,
      respectively, compared with a 29% decrease by LR-100. A decrease in systemic
      vascular resistance of 57% and 41% was observed with 0.017 and 0.05 mg/kg doses
      of centhaquin, respectively, compared with a 6% decrease by LR-100. LR-100
      decreased cardiac output (CO) by 28%, whereas 0.017 and 0.05 mg/kg doses of
      centhaquin increased it by 260% and 180%, respectively. LR-300 commonly used for
      resuscitation was found to increase MAP and CO. Compared with LR-300, centhaquin
      (0.05 mg/kg) significantly improved survival time, increased CO, and was
      effective in resuscitation of hemorrhaged rats. CONCLUSIONS: Centhaquin was found
      to be more effective than LR-300 as an effective resuscitative agent for the
      treatment of hemorrhagic shock in rat.

PMID- 22964271
TI  - Does residents' involvement in mastectomy cases increase operative cost? If so,
      who should bear the cost?
AB  - INTRODUCTION: It is a widely held belief that surgical residents' involvement in
      operative cases increases operative time and costs. However, there is little
      published data regarding the veracity of this belief, and there is poor
      documentation of the actual costs associated with involving surgical residents in
      operative cases. This report represents a retrospective analysis of the
      additional cost associated with involving surgical residents of all training
      years in mastectomy cases over a 6-y period. METHODS: A total of 1063 mastectomy
      cases (with and without reconstruction) were performed over a 6-y period (2004
      2010) at the Saint Barnabas Medical Center, Livingston, NJ. Data relating to the
      type of mastectomy performed, operative times, training level of residents
      involved, and the surgical attendings' case volume were collected. Two major
      groups (attendings-only and attendings with residents) and 19 mastectomy
      subcategories were formed. Differences in operating room (OR) times between the
      attendings-only and attendings with residents groups were multiplied by the
      hospital OR charges per minute of time ($15/min after the initial 30 min) to
      determine the additional operative costs associated with residents' involvement.
      The impact of postgraduate training year and the attendings' case volume on
      operative time was analyzed separately. Statistical analysis was conducted using
      IBM SPSS 18.0.1 Windows version (PASW Statistics for Windows, SPSS Inc, Chicago).
      RESULTS: Twenty-six surgeons and 97 residents were involved in 1063 mastectomy
      cases. Eight hundred ninety-five cases involved residents, of which 405 cases had
      reconstruction and 490 cases did not. Among 168 cases involving residents, 107
      cases had reconstruction and 61 cases did not. The mean OR time was increased in
      nearly all cases involving surgical residents but statistically significant in
      only nine of the 19 mastectomy subcategories. Postgraduate year (PGY) 1 or PGY2
      residents increased OR time for unilateral mastectomy, whereas the involvement of
      PGY1 through PGY3 residents increased OR time for bilateral
      mastectomy+reconstruction (P<0.05). No significant difference was observed when
      PGY4 and PGY5 were involved in mastectomy cases. The additional calculated time
      required to perform mastectomies involving surgical residents was 41,366 min,
      which corresponded to an increase in OR costs of $620,340 over 6 y. CONCLUSION:
      The involvement of surgical residents in mastectomy cases significantly increases
      operative times and cost. This difference is most apparent when junior-level
      residents are involved and disappears by the PGY4-PGY5. Increased operative costs
      and the lost opportunity costs for surgical attendings are significant issues
      associated with residency education. Center for Medicare and Medicaid Services
      and Accreditation Council on Graduate Medical Education should consider such data
      when establishing appropriate reimbursements for graduate training programs.

PMID- 22964272
TI  - Home-based overnight transcutaneous capnography/pulse oximetry for diagnosing
      nocturnal hypoventilation associated with neuromuscular disorders.
AB  - OBJECTIVE: To determine the utility of home-based, unsupervised transcutaneous
      partial pressure of carbon dioxide (tc-Pco(2)) monitoring/oxygen saturation by
      pulse oximetry (Spo(2)) for detecting nocturnal hypoventilation (NH) in
      individuals with neuromuscular disorders. DESIGN: Retrospective case series
      analyzed consecutively. SETTING: Multidisciplinary neuromuscular respiratory
      failure (NMRF) clinic at an academic institution. PARTICIPANTS: Subjects (N=35,
      68.6% men; mean age, 46.9y) with spinal cord injury (45.7%) or other
      neuromuscular disorders underwent overnight tests with tc-Pco(2)/Spo(2)
      monitoring. Fifteen (42.9%) were using nocturnal ventilatory support, either
      bilevel positive airway pressure (BiPAP) or tracheostomy ventilation (TV).
      INTERVENTIONS: A respiratory therapist brought a calibrated tc-Pco(2)/Spo(2)
      monitor to the patient's home and provided instructions for data collection
      during the subject's normal sleep period. Forced vital capacity (FVC), body mass
      index (BMI), and exhaled end-tidal Pco(2) (ET-Pco(2)) were recorded at a clinic
      visit before monitoring. MAIN OUTCOME MEASURES: Detection of NH (tc-Pco(2)
      >=50mmHg for >=5% of monitoring time). Data were also analyzed to determine
      whether nocturnal oxygen desaturation (Spo(2) <=88% for >=5% of monitoring time),
      FVC, BMI, or daytime ET-Pco(2) could predict the presence of NH. RESULTS: NH was
      detected in 18 subjects (51.4%), including 53.3% of those using BiPAP or TV. NH
      was detected in 43.8% of ventilator-independent subjects with normal daytime ET
      Pco(2) (present for 49.4%+/-31.5% [mean +/- SD] of the study period), and in 75%
      of subjects with an elevated daytime ET-Pco(2) (present for 92.3%+/-8.7% of the
      study period). Oxygen desaturation, BMI, and FVC were poor predictors of NH. Only
      3 attempted monitoring studies failed to produce acceptable results. CONCLUSIONS:
      Home-based, unsupervised monitoring with tc-Pco(2)/Spo(2) is a useful method for
      diagnosing NH in NMRF.

PMID- 22964273
TI  - Association study of polymorphisms in the receptor for advanced glycation end
      products (RAGE) gene with susceptibility and prognosis of heart failure.
AB  - BACKGROUND: Functional polymorphisms in the receptor for advanced glycation end
      products (RAGE) gene have been implicated in several vascular diseases. However,
      to date, no study investigated the association of RAGE polymorphisms with heart
      failure (HF). OBJECTIVE: In this study we tested the hypothesis that the 63-bp
      insertion/deletion, the -374T>A (rs1800624) and the -429T>C (rs1800625)
      polymorphisms in the RAGE gene might be associated with susceptibility to HF and
      could predict all-cause mortality in Brazilian outpatients with left ventricular
      systolic dysfunction. METHODS: A total of 273 consecutive HF patients (196
      Caucasian- and 77 African-Brazilians) and 334 healthy blood donors (260 Caucasian
      and 74 African-Brazilians) were enrolled in a tertiary care university hospital.
      Genotyping of RAGE polymorphisms was done by polymerase chain reaction (PCR) or
      PCR followed by enzyme restriction analysis. RESULTS: The allele, genotype and
      haplotype frequencies of -374T>A and -429T>C polymorphisms were not significantly
      different between HF patients and healthy blood donors in both ethnic groups.
      However, among African-Brazilians, the frequency of carriership of the del allele
      was lower in HF patients than in blood donors (2.6% vs 12.2%, respectively,
      p=0.008). Patients were followed-up for a median of 38 months and the survival
      analysis did not reveal a consistent association between RAGE polymorphisms and
      all-cause death in both ethnic groups. CONCLUSION: The -374T>A and -429T>C
      polymorphisms in the RAGE gene were not associated with the susceptibility and
      prognosis of HF. Notwithstanding, the 63-bp ins/del polymorphism might be
      involved in the susceptibility to HF in African-Brazilians.

PMID- 22964274
TI  - Replication timing in a single human chromosome 11 transferred into the Chinese
      hamster ovary (CHO) cell line.
AB  - DNA replication in eukaryotes initiates from discrete genomic regions, termed
      origins, according to a strict and often tissue-specific temporal program.
      However, the genetic program that controls activation of replication origins has
      still not been fully elucidated in mammalian cells. Previously, we measured
      replication timing at the sequence level along human chromosomes 11q and 21q. In
      the present study, we sought to obtain a greater understanding of the
      relationship between replication timing programs and human chromosomes by
      analysis of the timing of replication of a single human chromosome 11 that had
      been transferred into the Chinese hamster ovary (CHO) cell line by chromosome
      engineering. Timing of replication was compared for three 11q chromosomal regions
      in the transformed CHO cell line (CHO(h11)) and the original human fibroblast
      cell line, namely, the R/G-band boundary at 11q13.5/q14.1, the centromere and the
      distal telomere. We found that the pattern of replication timing in and around
      the R/G band boundary at 11q13.5/q14.1 was similar in CHO(h11) cells and
      fibroblasts. The 11q centromeric region, which replicates late in human
      fibroblasts, replicated in the second half of S phase in CHO(h11) cells. By
      contrast, however, the telomeric region at 11q25, which is late replicating in
      fibroblasts (and in several other human cell lines), replicated in the first half
      of S phase or in very early S phase in CHO(h11) cells. Our observations suggest
      that the replication timing programs of the R/G-band boundary and the centromeric
      region of human chromosome 11q are maintained in CHO(h11) cells, whereas that for
      the telomeric region is altered. The replication timing program of telomeric
      regions on human chromosomes might be regulated by specific mechanisms that
      differ from those for other chromosomal regions.

PMID- 22964275
TI  - Does cytochrome P450 1A1 MspI polymorphism increase acute lymphoblastic leukemia
      risk? Evidence from 2013 cases and 2903 controls.
AB  - Previous studies indicated that cytochrome P450 1A1 (CYP1A1) MspI polymorphism
      might be a possible risk factor for several malignancies. Increasing
      investigations have been conducted on the association of CYP1A1 MspI
      polymorphisms with acute lymphoblastic leukemia (ALL). However, the results were
      controversial. The goal of the present study was to address this controversy by
      pooling and analyzing the published data. Therefore, quantitative meta-analyses
      evaluating the association of CYP1A1 MspI variation with ALL were performed and
      subgroup analyses on ethnicity, age groups and source of controls were further
      carried out. After a rigorous search in the Medline, EMBASE, OVID, ScienceDirect,
      and CNKI databases, all eligible studies for the period up to May 2012 were
      identified and screened according to the inclusion and exclusion criteria.
      Consequently, a total of fourteen case-control studies including 2013 cases and
      2903 controls were selected for analysis. The overall data indicated a
      significant association of CYP1A1 MspI polymorphism with ALL risk (CC+TC vs TT:
      OR=1.33; 95%CI=1.05-1.69). In a subgroup analysis according to ethnicity, no
      associations were shown among Asians, Caucasians and Mixed ethnicity subgroups.
      In the subgroup analysis regarding age groups, increased risk was observed in the
      childhood ALL subgroup (C vs T: OR=1.23; 95%CI=1.04-1.45; CC+TC vs TT: OR=1.31;
      95%CI=1.08-1.59). In the subgroup analysis stratified by source of controls,
      significant associations were observed in the population-based subgroup (CC+TC vs
      TT: OR=1.33; 95%CI=1.03-1.71). In conclusion, the results of the present study
      suggest that CYP1A1 MspI polymorphism might be a risk factor for ALL,
      particularly childhood ALL. Future well-designed high quality investigations with
      large sample sizes are required to elucidate the gene polymorphism-ALL
      relationship and gene-environment interactions.

PMID- 22964276
TI  - Atypical development of spontaneous social cognition in autism spectrum
      disorders.
AB  - Individuals with autism spectrum disorders (ASD) have profound impairment in the
      development of social interaction and communication. However, it is also known
      that some 'high-functioning' individuals with ASD show apparently typical
      capacity to process social information in a controlled experimental settings,
      despite their difficulties in daily life. The current paper overviews the
      spontaneous social cognition, spontaneous processing of social information in the
      absence of explicit instruction or task demand, in individuals with ASD. Three
      areas of the researches, false belief attribution, imitation/mimicry, and eye
      gaze processing, have been reviewed. The literatures suggest that high
      functioning individuals with ASD (a) do not spontaneously attribute false belief
      to others, even though they can easily do so when explicitly instructed, (b) can
      imitate others' goal-directed actions under explicit instruction and show
      spontaneous mimicry of others' actions when they attend to the action, but are
      less likely to show spontaneous mimicry without the task structure to navigate
      attention to others' action and (c) can process others' gaze direction and shift
      attention to others' gaze directions, but fail to spontaneously attend to another
      person's eyes in social and communicative context, and less likely to be prompted
      to respond in response to perceived eye contact. These results are consistent
      with the claim that individuals with ASD do not spontaneously attend to socially
      relevant information, even though they can easily process the same information
      when their attention is navigated towards it.

PMID- 22964277
TI  - Protect the unprotected: neonatal sepsis in very-low-birth-weight infants.

PMID- 22964278
TI  - Role of leukotriene receptor antagonists in asthma.

PMID- 22964279
TI  - Preliminary report on admission profiles for children under 5 years old in
      Taiwan: disparities between 2000 and 2009.
AB  - BACKGROUND/PURPOSE: Data on hospital admissions for children under 5 years old,
      concerning the admission rate, leading diagnoses, categories of disease, average
      hospitalization days, costs and between-year differences are scarce. Our study
      aims to investigate such admission profiles. METHODS: Five percent of admission
      data for children under 5 years old in 2000 and 2009 was collected from the
      National Health Insurance Research Database in Taiwan. We calculated the
      admission rate in regards to total admission, the patients' gender, the ten
      leading diagnoses, the ten most systemic common categories of disease, and the
      average hospitalization days and costs. The differences of the rates between 2000
      and 2009 were evaluated by incidence rate ratios (IRR). RESULTS: The admission
      rate per thousand children (population) was higher in 2009 (172.9) than 2000
      (153.1). The ten most common systemic categories of disease were similar in both
      years. Furthermore, it was observed that the hospitalization days decreased by
      3.7% in 2009, while medical expenditures increased by 10.9%. CONCLUSIONS: Efforts
      should be made to decrease the admission rate and hospitalization days in Taiwan
      to the levels of well-developed countries. Our data may serve as baseline data
      for future evaluations of child morbidity.

PMID- 22964280
TI  - Prevalence and pathogen distribution of neonatal sepsis among very-low-birth
      weight infants.
AB  - BACKGROUND: Neonatal sepsis contributes to great mortality and morbidity among
      very-low-birth-weight (VLBW) infants. Prevalence and pathogen distribution of
      sepsis in the neonatal intensive care units (NICUs) vary with time and geographic
      location. Such information serves as a guide for selection of empirical
      antibiotics coverage. METHODS: This is a case series study performed by
      retrospective chart review of VLBW infants (birth body weight, BBW, <1500 g) in a
      medical center during a 5-year period from January 2005 to December 2009.
      Episodes of positive blood cultures, pathogen distribution and related clinical
      manifestations were described. RESULTS: A total of 158 episodes of sepsis were
      identified from 1042 VLBW infants. Sepsis rate was 152 per 1000 live births. The
      vast majority of infections (60.7%) were caused by Gram-positive organisms
      [G(+)], and overall Coagulase-negative staphylococci (CoNS) (52.5%) were the most
      common pathogen identified. Prevalence for early-onset sepsis (EOS) was 1% and
      for late-onset sepsis (LOS) was 14.2%. Infants with EOS had a much higher case
      fatality rate than LOS (40% vs. 4.7%). Escherichia coli (40%) were the leading
      pathogen of EOS while CoNS (54.7%) was the leading pathogens of LOS. Overall,
      apnea and/or bradycardia and/or cyanosis (65.8%), poor activity (48.7%), and
      increased respiratory effort (43.0%) were the most common presenting features of
      sepsis. CONCLUSION: Unlike term infants, Gram-negative organism and E coli were
      the leading pathogen of EOS among VLBW infants. Judicious and timely use of
      antibiotic therapy is crucial in the care of VLBW infants.

PMID- 22964281
TI  - Effect of selective cysteinyl leukotriene receptor antagonists on airway
      inflammation and matrix metalloproteinase expression in a mouse asthma model.
AB  - BACKGROUND: Cysteinyl leukotrienes (CysLTs) play a major role in the pathogenic
      changes of airway inflammation in asthma treatment. The matrix metalloproteinase
      (MMP) family, especially MMP-9 and MMP-2 levels, can reflect the status of airway
      remodeling. This study was undertaken to determine the role of a specific CysLT
      receptor antagonist in inhibition of airway inflammation and reversal of airway
      remodeling. METHODS: Ovalbumin (OVA)-sensitized BALB/c mice were fed with a
      specific leukotriene receptor antagonist (MK-679), prednisolone or placebo from
      Days 15 to 27. Airway hyperreactivity, bronchoalveolar lavage fluid (BALF), and
      sera were analyzed. Pulmonary histology was obtained, and the levels of MMP-2 and
      MMP-9 in BALF were measured. RESULTS: The OVA-sensitized mice developed
      significant airway inflammatory responses, including extensive eosinophils
      trafficking into BALF and lung interstitium, goblet cell hyperplasia, mucus
      hypersecretion, elevated serum immunoglobulin (Ig) E, and decreased level of
      serum IgG2a. Administration of MK-679 could reduce airway inflammation but was
      not as effective as prednisolone. However, MK-679 was more effective than
      prednisolone for reversing subepithelial fibrotic and myofibrotic reactions of
      airway remodeling. The levels of MMP-2 and -9 in BALF were proportional to the
      extent of airway remodeling, which can reflect the effects of treatment. Both
      prednisolone and MK-679 reverse airway hyperresponsiveness induced by OVA
      sensitized mice. CONCLUSION: Cysteinyl leukotriene receptor plays a more
      important role than CysLT in the pathogenesis of allergic airway inflammation.
      MMP-2 and -9 may be more sensitive indicators of airway remodeling.

PMID- 22964282
TI  - A strategy for reduction of antibiotic use in new patients admitted to a neonatal
      intensive care unit.
AB  - BACKGROUND: In order to reduce the unnecessary use of and provide appropriate
      guidance for the administration of antibiotics, the neonatal bacterial infections
      screening score (NBISS) was developed to assess each new patient that is admitted
      to the neonatal intensive care unit (NICU). METHODS: NBISS was designed based on
      maternal risk factors, clinical presentations, and laboratory data. The total
      score of each new patient is calculated at the time of admission. The first
      period of this study was an observational survey. Receiver operating
      characteristic (ROC) curves were used to determine the best cut-off NBISS for the
      diagnosis of bacterial infection (BI) and guide the use of antibiotics during the
      second period of this study. RESULTS: Of 250 neonates who were admitted to the
      NICU, 237 (94.8%) received antibiotics during the first period of study. The
      initial total scores were not statistically different between the BI and non-BI
      groups (p = 0.155). We weighted C-reaction protein (CRP) (by 8*), the presence of
      a bulging fontanelle, pus from the ear canal, redness around the umbilicus,
      reduced movement, and being unable to feed (each by 5*) as significantly
      different between the BI and non-BI groups (p = 0.015). Weighted scores >8 points
      demonstrated the best diagnostic accuracy for indicating BI. After introducing
      NBISS for predicting BI in new patients admitted to NICU, the rate of antibiotic
      use significantly decreased from 94.8% to 60.3% between the two periods.
      CONCLUSION: Using this simple screening strategy, we were able to clinically
      reduce the use of unnecessary antibiotics.

PMID- 22964283
TI  - Constipation is a major complication after posterior sagittal anorectoplasty for
      anorectal malformations in children.
AB  - BACKGROUND: To assess whether constipation or fecal incontinence is a major late
      complication after posterior sagittal anorectoplasty in patients with anorectal
      malformation (ARM). METHODS: We retrospectively enrolled 188 children, 85 low
      type ARM (L-ARM) and 103 high-type ARM (H-ARM), who had complete medical records
      of bowel habits and medication histories after posterior sagittal anorectoplasty
      for anorectal malformation in Mackay Memorial Hospital. Stool characteristics as
      well as physical and medication history were evaluated. The symptom severity (SS)
      scoring system was used to assess changes in bowel habits. RESULTS: During a mean
      follow-up period of 4.3 years, constipation was found to be the most common late
      complication in both groups of patients (64.5% in the L-ARM group and 78.6% in
      the H-ARM group). Compared to constipation, stool incontinence was much less
      frequent, with 4.7% in L-ARM and 3.9% in H-ARM. There was no significant
      difference in mean SS scores between the two groups. CONCLUSION: Constipation was
      the most common late sequela in children after correction of ARM in our study.

PMID- 22964284
TI  - Epidemiology, clinical features, treatment, and outcomes of cases of influenza A
      infection during the 2009 influenza pandemic in northern Taiwan.
AB  - BACKGROUND: In April 2009, confirmed cases of influenza A (H1N1) infections were
      reported worldwide, spreading from Mexico and southern California. In order to
      determine the clinical features of patients infected with this virus before
      vaccine implementation and evaluate the response of antiviral treatment in
      Taiwan, we reviewed medical charts and collected clinical data from outpatients
      and inpatients at the Tao-Yuan General Hospital. METHODS: From May 19, 2009, to
      October 31, 2009, clinical data from patients confirmed by the rapid antigen
      screening test for influenza A virus and/or reverse transcriptase-polymerase
      chain reaction analysis at the Tao-Yuan General Hospital were reviewed
      retrospectively. RESULTS: A total of 1158 patients (94.6%) received outpatient
      management, 66 patients (5.4%) were hospitalized, and no patients died. More than
      two-thirds of patients were younger than 16 years old. The most common symptoms
      were fever (99.8%), cough (91.4%), sore throat (63.7%), and rhinorrhea (53.8%).
      Ninety patients (13.3%) had complications, including lower respiratory tract
      infections (11.1%). Among the 677 patients receiving follow-ups, none needed
      mechanical ventilation due to lower respiratory tract infection. Most of the
      patients (87.2%) began antiviral therapy within 2 days after the onset of
      symptoms. Ninety percent of patients became afebrile within 2 days after the
      initiation of antiviral therapy. The number of screening specimens and the
      positivity rate of the rapid influenza A antigen test were dramatically decreased
      4 weeks later, after universal implementation of the pandemic influenza A (H1N1)
      2009 vaccine to infants and school-age children. CONCLUSION: The clinical
      spectrum of pandemic influenza A (H1N1) 2009 infection was broad and the severity
      of disease was mild. Early antiviral treatment was effective in decreasing
      mortality and morbidity. Early and universal implementation of a novel influenza
      A vaccine is an effective approach for preventing pandemic community influenza
      outbreaks, particularly among infants and school-age children.

PMID- 22964285
TI  - A novel 3670-base pair mitochondrial DNA deletion resulting in multi-systemic
      manifestations in a child.
AB  - Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects
      to oxidative phosphorylation. The common clinical presentations of mtDNA deletion
      vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome,
      and progressive external ophthalmoplegia. Here, we report the case of a 10-year
      old boy who presented with progressive deterioration of his clinical status
      (which included hypoglycemia, short stature, sensorineural hearing loss,
      retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed
      to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and
      acute encephalopathy. Following treatment, the patient was stabilized and his
      neurological condition improved. Through a combination of histological
      examinations and biochemical and molecular analyses, mitochondrial disease was
      confirmed. A novel 3670-base pair deletion (deletion of mtDNA nt 7,628-11,297)
      was identified in the muscle tissue. A direct repeat of CTACT at the breakpoints
      was also detected.

PMID- 22964286
TI  - Valsalva sinus aneurysm of the non-coronary cuspid presenting as cyclops sign on
      multi-detector computed tomography.
AB  - An 8-year-old girl with Williams syndrome was found to have a heart murmur.
      Cardiac CT demonstrated a Valsalva sinus aneurysm (VSA) of the non-coronary
      cuspid, with left atrium (LA) indentation, resembling the face of Cyclops on a
      coronal reformatted image. Williams syndrome is related to some congenital
      disorders with interruption of the tunica media from the aortic root to the
      annular fibrous ring or aortic valve. However, it rarely presents at birth. The
      sinus of Valsalva dilates as time goes by, due to the persistent striking force
      from the left ventricle (LV). However, it is silent until rupture when cardiac
      tamponade occurs. The typical imaging appearance of VSA is of a saccular shape
      and originates above the aortic root, but sometimes involves the entire sinus.
      Although lethal complications of VSA occur without warning, prophylactic surgical
      intervention remains controversial. Regular imaging follow-up is advised before
      complications occur.

PMID- 22964287
TI  - CTX-M-producing Escherichia coli and Klebsiella pneumoniae isolated from
      community-acquired urinary tract infections in Valledupar, Colombia.
AB  - OBJECTIVE: Describe the presence of CTX-M-1 phylogenetic subgroup extended
      spectrum beta-lactamases (ESBL), associated with TEM and SHV genes, and the gene
      encoding cephalosporinase, CMY-2 in Escherichia coli and Klebsiella pneumoniae
      isolates from community-acquired urinary tract infections. METHODS: 102 E. coli
      and 21K. pneumoniae were collected from patients with culture-proven urinary
      tract infection (UTI), during February and March, 2011. Antimicrobial
      susceptibility test was performed by disk diffusion according to the standards of
      the Clinical Laboratory Standard Institute. Screening for cephalosporins
      resistant E. coli and K. pneumoniae was performed by PCR assay for bla(TEM),
      bla(SHV), bla(CTX-M-1),(-2),(-8),(-9), bla(PER-2) and bla(CMY-2) genes.
      Statistical analysis was performed by chi-squared test and multivariate logistic
      regression analysis. RESULTS: ESBL production was detected in 12 (11.7%) E. coli
      and four (19%) K. pneumoniae isolates. TEM ESBLs were detected in seven E. coli
      and three K. pneumoniae isolates. SHV ESBLs were found in four K. pneumoniae
      isolates. CTX-M-1 phylogenetic subgroup was positive in seven E. coli and three
      K. pneumoniae isolates. CMY-2 beta-lactamase gene was detected in nine E. coli
      and one K. pneumoniae isolates. A significant association of ESBL expression in
      E. coli was observed with resistance to tobramycin (p<=0.001), tetracycline
      (p=0.043), and ciprofloxacin (p<=0.001). In K. pneumoniae isolates, significant
      association was found with resistance to tobramycin and ciprofloxacin (p=0.006),
      and trimethoprim-sulfamethoxazole (p=0.043). Multivariate analyses did not show
      association between ESBL production in E. coli and K. pneumoniae, and resistance
      to non-beta-lactams drugs. CONCLUSIONS: CTX-M ESBL in uropathogens isolated from
      the community is cause for concern due to the enormous potential for multidrug
      resistance from strains that produce these enzymes, which could lead to failure
      of empirically-administered therapies and development of complicated UTIs.

PMID- 22964288
TI  - Mycobacterium tuberculosis meningitis as the first presentation of chronic
      granulomatous disease.

PMID- 22964289
TI  - Etiologic and epidemiologic analysis of hand, foot, and mouth disease in
      Guangzhou city: a review of 4,753 cases.
AB  - OBJECTIVES: This study aimed to review etiological and epidemiological data for
      hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in
      Guangzhou City, to help develop and implement precautionary measures applicable
      for future outbreaks. METHODS: The characteristics of 4,753 HFMD episodes were
      retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the
      Guangdong Women and Children's Hospital, which is the national enterovirus
      monitoring agent and the designated hospital in China for treating severe HFMD.
      RESULTS: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized;
      60% were males. Most patients (93.8%) were children under 5 years old, with a
      median age at onset of 2.4 years. HFMD incidence peaked in April/May and
      September/October. From the total, 1,067 (22.4%) infections were positive for
      human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16
      (CA16), and 941 (19.8%) were positive for other common enteroviruses. In
      contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common
      enteroviruses. Cross-correlation coefficients demonstrated associations between
      the number of cases, seasonal temperatures, and humidity. Among hospitalized
      cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were
      positive for HEV71. CONCLUSION: Seasonal fluctuations and HEV71 and CA16 were the
      two key factors influencing the Guangzhou HFMD epidemic. The infection
      predominantly affected children younger than 5 years old.

PMID- 22964290
TI  - Thyroid dysfunction in Turkish patients with chronic hepatitis C receiving
      peginterferon plus ribavirin in the period of 2005-2010.
AB  - Interferon-alpha based therapy for chronic hepatitis C (CHC) is associated with
      thyroiditis and thyroid dysfunction (TD). This study investigated whether TD
      during pegylated interferon-alpha (PEG-IFN) plus ribavirin treatment favors
      sustained viral response (SVR), and also the association between TD and PEG-IFN
      formulations. This retrospective study was performed in CHC patients who had
      received PEG-IFN plus ribavirin and had been followed for six months after
      treatment. Several factors were compared between patients with and without TD.
      119 patients were included in the study. De novo incidence of TD was found to be
      16.8%, and 16 of the 18 patients with TD achieved SVR. Although this rate was
      higher than patients without TD according to univariate analysis, logistic
      regression analysis revealed that there was not a significant association between
      TD and SVR, whereas baseline thyroperoxidase antibody (anti-TPO) positivity was
      the only significant predictor of TD. Moreover, TD was not associated with PEG
      IFN type. Both interferon-alpha and hepatitis C virus (HCV) contribute to TD
      during antiviral therapy. It seems that there is no association between thyroid
      toxicity and viral clearance or type of PEG-IFN; however, anti-TPO positivity
      before treatment is the strongest predictor for TD during antiviral therapy.

PMID- 22964291
TI  - Evaluation of rapid tests for human immunodeficiency virus as a tool to detect
      recent seroconversion.
AB  - The identification of recent HIV infection is important for epidemiological
      studies and to monitor the epidemic. The objective of this study was to evaluate
      two rapid tests that are easily available to the Brazilian scientific community
      for using as markers of recent HIV infection. The Rapid Test - HIV-1/2 Bio
      Manguinhos (Bio-Manguinhos/Fiocruz, Brazil) and the Rapid Check HIV 1&2 (NDI
      UFES, Center for Infectious Diseases, Universidade Federal do Espirito Santo)
      were tested, using 489 samples with HIV positive serology, from blood donors,
      previously classified as recent or long-term infection by serological testing
      algorithm for recent HIV seroconversion (STARHS) or LS-HIV Vitros assay methods.
      The samples were diluted prior to testing (1:50 and 1:100 for the Rapid Test -
      HIV-1/2 Bio-Manguinhos, and 1:500 and 1:600 for the Rapid Check HIV 1&2).
      Negative samples were considered recent infection, whereas those showing any
      color intensity were associated with long-term infection. The best dilutions were
      1:100 for HIV-1/2 Bio-Manguinhos test (Kappa = 0.840; overall agreement = 0.93),
      and 1:500 for the Rapid Check HIV 1&2 (Kappa = 0.867; overall agreement = 0.94).
      The results suggest that both rapid tests can be used to detect recent
      seroconversion.

PMID- 22964292
TI  - Paracoccidioidomycosis in pregnancy: an atypical case report.

PMID- 22964293
TI  - Autoimmune and dengue fever.

PMID- 22964294
TI  - Community-acquired methicillin-resistant Staphylococcus aureus from skin and soft
      tissue infections (in a sample of Egyptian population): analysis of mec gene and
      staphylococcal cassette chromosome.
AB  - BACKGROUND: Staphylococcus aureus has been recognized as an important pathogen
      associated with inpatients and community infections. Community-acquired
      methicillin-resistant S. aureus (CA-MRSA) infections commonly present as skin and
      soft-tissue infections (SSTIs). Treatment often includes incision and drainage
      with or without adjunctive antibiotics. OBJECTIVES: This study aimed to identify
      CA-MRSA infections both phenotypically and genotypically, to determine their
      spectrum of antibiotic resistance, and to establish the best scheme for molecular
      distinction between hospital-acquired MRSA (HA-MRSA) and CA-MRSA by
      staphylococcal cassette chromosome mec (SCCmec) typing and detection of Panton
      Valentine leukocidin (PVL). MATERIALS: 50 swabs, from skin and soft tissue of
      infected lesions of outpatients attending the dermatology department of the
      Medical School, Alexandria University, were collected. Additionally, a nasal swab
      was taken from every participant. METHODS: Collection of swabs from the infected
      skin and soft tissues, followed by laboratory testing to phenotypically and
      genotypically identify MRSA. Also, nasal swabs were taken from every patient to
      identify MRSA colonization. RESULTS: Staphylococcus aureus strains were
      identified in 38 (76%) of the 50 clinical isolates. 18 (47.37%) out of the 38 S.
      aureus strains were resistant to oxacillin and cefoxitin discs, were penicillin
      binding protein 2a (PBP2a) producers, and were initially diagnosed as MRSA. All
      of the 18 strains were definitively diagnosed as MRSA by mecA gene detection
      using real time PCR, while only six (33.33%) strains were PVL positive. Using the
      sets of primers of Zhang et al.: nine (50%) out of the 18 CA-MRSA strains were
      SCCmec type V, and one (5.56%) was SCCmec type IVc. Then, using the set of
      primers by Oliveira et al., two (25%) out of the eight untypable MRSA strains
      were found to be SCCmec type IV, and six (75%) remained untypable. CONCLUSIONS:
      CA-MRSA must be considered when treating skin and soft tissue infections,
      especially in developing countries. Empirical use of agents active against CA
      MRSA is warranted for patients presenting with serious SSTIs.

PMID- 22964295
TI  - Seroprevalence of hepatitis A immunity among children and adolescents in two
      cities of the Triangulo Mineiro region, state of Minas Gerais, Brazil.

PMID- 22964296
TI  - Clinical correlation between Treponema pallidum infection and agenesis of the
      gallbladder.

PMID- 22964298
TI  - The Tower of Babel of liver metastases from colorectal cancer: are we ready for
      one language?
AB  - Advances in surgical and medical treatments have significantly changed the
      management of colorectal cancer liver metastases (CRCLMs). In particular, new
      drugs and modern combination chemotherapy regimens, together with the improvement
      of surgical techniques, allow a potentially curative approach in an increasing
      number of patients. Nevertheless, there is no strong evidence for an optimal
      treatment strategy for CRCLMs, mainly because of the extensive heterogeneity in
      the patients. In fact, although we consider them a population, they represent
      different clinical and biological subtypes requiring different approaches.
      Furthermore, results from different studies in this setting may be difficult to
      interpret, also because the definitions of different patient subgroups are
      unclear and overlapping. In this review we discuss the results of clinical trials
      evaluating the role of chemotherapy in the multimodal management of CRCLMs, in
      either the pre- or postoperative setting. Then we identify three main categories
      of CRCLM patients, providing clinical recommendations for each.

PMID- 22964297
TI  - Age-related cataracts: homocysteine coupled endoplasmic reticulum stress and
      suppression of Nrf2-dependent antioxidant protection.
AB  - To determine whether high levels of homocysteine (Hcy) induce endoplasmic
      reticulum (ER) stress with suppression of the nuclear factor-erythroid-2-related
      factor 2 (Nrf2)-dependent antioxidant protection in lens epithelial cells (LECs).
      ER stress was acutely induced by exposure of LECs to 100 MUM Hcy without FCS and
      also by exposure to 5 mM Hcy with 10% FCS. After exposure to Hcy, significant
      changes were found in P-PERK, P-eIF2alpha, XBP1, Nrf2, and Keap1 within 24 h. The
      production of reactive oxygen species (ROS) was increased after Hcy exposure. The
      downstream enzymes of Nrf2 like, catalase, and glutathione reductase, were
      significantly decreased. These results suggested that the Hcy-induced ER stress
      suppressed the Nrf2-dependent antioxidant protection and simultaneously generated
      ROS which resulted in further oxidation and death of LECs. The loss of Nrf2 is
      mainly due to proteosomal degradation and m-calpain activation by the increased
      levels of cytoplasmic Ca(++). The caspases also play a role in the degradation of
      Nrf2. Our findings demonstrated that high levels of Hcy induce ER stress, chronic
      UPR, alter the levels of UPR specific proteins, increase the production of ROS,
      degrade Nrf2 and block the Nrf2-dependent antioxidant defense protection in LECs.
      Thus, the upregulation of ROS might exceed the Nrf2 dependent antioxidant defense
      protection in the LECs and result in the highly oxidized lenses and resulted in
      ARCs.

PMID- 22964299
TI  - Molecular biology in breast cancer: should molecular classifiers be assessed by
      conventional tools or by gene expression arrays?
AB  - Breast cancer is a complex disease, with heterogeneous presentations and clinical
      courses. Standard clinico-pathological parameters, relying on single gene or
      protein characterization determined with sometimes poorly-reproducible
      technologies, have shown limitations in the classification of the disease and in
      the prediction of individual patient outcomes and responses to therapy. Gene
      expression profiling has revealed great potential to accurately classify breast
      cancer and define patient prognosis and prediction to anti-cancer therapy.
      Nevertheless, the performance of molecular classifiers remains sub-optimal, and
      both technical and conceptual improvements are needed. It is likely that
      determining the ideal strategy for tailoring treatment of breast cancer will
      require a more systematic, structured and multi-dimensional approach than in the
      past. Besides implementing cutting-edge technologies to detect genetic and
      epigenetic cancer alterations, the future of breast cancer research will in all
      probability rely on the innovative and multilevel integration of molecular
      profiles with clinical parameters of the disease and patient-related factors.

PMID- 22964300
TI  - Programmatic features of aging originating in development: aging mechanisms
      beyond molecular damage?
AB  - The idea that aging follows a predetermined sequence of events, a program, has
      been discredited by most contemporary authors. Instead, aging is largely thought
      to occur due to the accumulation of various forms of molecular damage. Recent
      work employing functional genomics now suggests that, indeed, certain facets of
      mammalian aging may follow predetermined patterns encoded in the genome as part
      of developmental processes. It appears that genetic programs coordinating some
      aspects of growth and development persist into adulthood and may become
      detrimental. This link between development and aging may occur due to regulated
      processes, including through the action of microRNAs and epigenetic mechanisms.
      Taken together with other results, in particular from worms, these findings
      provide evidence that some aging changes are not primarily a result of a build-up
      of stochastic damage but are rather a product of regulated processes. These
      processes are interpreted as forms of antagonistic pleiotropy, the product of a
      "shortsighted watchmaker," and thus do not assume aging evolved for a purpose.
      Overall, it appears that the genome does, indeed, contain specific instructions
      that drive aging in animals, a radical shift in our perception of the aging
      process.

PMID- 22964301
TI  - Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1
      FPR2/ALX anti-inflammatory system.
AB  - Unregulated inflammation underlies many diseases, including sepsis. Much interest
      lies in targeting anti-inflammatory mechanisms to develop new treatments. One
      such target is the anti-inflammatory protein annexin A1 (AnxA1) and its receptor,
      FPR2/ALX. Using intravital videomicroscopy, we investigated the role of AnxA1 and
      FPR2/ALX in a murine model of endotoxin-induced cerebral inflammation
      [intraperitoneal injection of lipopolysaccharide (LPS)]. An inflammatory response
      was confirmed by elevations in proinflammatory serum cytokines, increased
      cerebrovascular permeability, elevation in brain myeloperoxidase, and increased
      leukocyte rolling and adhesion in cerebral venules of wild-type (WT) mice, which
      were further exacerbated in AnxA1-null mice. mRNA expression of TLR2, TLR4, MyD
      88, and Ly96 was also assessed. The AnxA1-mimetic peptide, AnxA1(Ac2-26) (100
      MUg/mouse, ~33 MUmol) mitigated LPS-induced leukocyte adhesion in WT and AnxA1
      null animals without affecting leukocyte rolling, in comparison to saline
      control. AnxA1(Ac2-26) effects were attenuated by Boc2 (pan-FPR antagonist, 10
      MUg/mouse, ~12 nmol), and by minocycline (2.25 mg/mouse, ~6.3 nmol). The
      nonselective Fpr agonists, fMLP (6 MUg/mouse, ~17 nmol) and AnxA1(Ac2-26), and
      the Fpr2-selective agonist ATLa (5 MUg/mouse, ~11 nmol) were without effect in
      Fpr2/3(-/-) mice. In summary, our novel results demonstrate that the AnxA1/FPR2
      system has an important role in effecting the resolution of cerebral inflammation
      in sepsis and may, therefore, provide a novel therapeutic target.

PMID- 22964302
TI  - Extraoral bitter taste receptors as mediators of off-target drug effects.
AB  - We present a novel hypothesis that could explain many off-target effects of
      diverse pharmaceuticals. Specifically, we propose that any drug with a bitter
      taste could have unintended actions in the body through stimulation of extraoral
      type 2 taste receptors (T2Rs). T2Rs were first identified in the oral cavity,
      where they function as bitter taste receptors. However, recent findings indicate
      that they are also expressed outside the gustatory system, including in the
      gastrointestinal and respiratory systems. T2R ligands include a diverse array of
      natural and synthetic compounds, many of which are toxins. Notably, many
      pharmaceuticals taste bitter, with compounds such as chloroquine, haloperidol,
      erythromycin, procainamide, and ofloxacin known to activate T2Rs. Bitter-tasting
      compounds can have specific physiological effects in T2R-expressing cells. For
      example, T2Rs are found in some gastrointestinal endocrine cells, including those
      that secrete the peptide hormones (e.g., ghrelin and glucagon-like peptide-1) in
      response to stimulation by bitter-tasting compounds. In the respiratory system,
      stimulation of T2Rs expressed in respiratory epithelia and smooth muscle has been
      implicated in protective airway reflexes, ciliary beating, and bronchodilation.
      If our hypothesis is confirmed, it would offer a new paradigm for understanding
      the off-target actions of diverse drugs and could reveal potential new
      therapeutic targets.

PMID- 22964303
TI  - Gravity-sensitive signaling drives 3-dimensional formation of multicellular
      thyroid cancer spheroids.
AB  - This study focused on the effects induced by a random positioning machine (RPM)
      on FTC-133 thyroid cancer cells and evaluated signaling elements involved in 3
      dimensional multicellular tumor spheroid (MCTS) formation. The cells were
      cultured on the RPM, a device developed to simulate microgravity, and under
      static 1-g conditions. After 24 h on the RPM, MCTSs swimming in culture
      supernatants were found, in addition to growth of adherent (AD) cells. Cells
      grown on the RPM showed higher levels of NF-kappaB p65 protein and apoptosis than
      1-g controls, a result also found earlier in endothelial cells. Employing
      microarray analysis, we found 487 significantly regulated transcripts belonging
      not only to the apoptosis pathway but also to other biological processes.
      Selected transcripts were analyzed with quantitative real-time PCR using the same
      samples. Compared with 1-g IL-6, IL-8, CD44, and OPN were significantly up
      regulated in AD cells but not in MCTSs, while ERK1/2, CAV2, TLN1, and CTGF were
      significantly down-regulated in AD cells. Simultaneously, the expression of ERK2,
      IL-6, CAV2, TLN1, and CTGF was reduced in MCTSs. IL-6 protein expression and
      secretion mirrored its gene expression. Thus, we concluded that the signaling
      elements IL-6, IL-8, OPN, TLN1, and CTGF are involved with NF-kappaB p65 in RPM
      dependent thyroid carcinoma cell spheroid formation.

PMID- 22964304
TI  - The GTPase Gem and its partner Kif9 are required for chromosome alignment,
      spindle length control, and mitotic progression.
AB  - Within the Ras superfamily, Gem is a small GTP-binding protein that plays a role
      in regulating Ca(2+) channels and cytoskeletal remodeling in interphase cells.
      Here, we report for the first time that Gem is a spindle-associated protein and
      is required for proper mitotic progression. Functionally, loss of Gem leads to
      misaligned chromosomes and prometaphase delay. On the basis of different
      experimental approaches, we demonstrate that loss of Gem by RNA interference
      induces spindle elongation, while its enforced expression results in spindle
      shortening. The spindle length phenotype is generated through deregulation of
      spindle dynamics on Gem depletion and requires the expression of its downstream
      effector, the kinesin Kif9. Loss of Kif9 induces spindle abnormalities similar to
      those observed when Gem expression is repressed by siRNA. We further identify
      Kif9 as a new regulator of spindle dynamics. Kif9 depletion increases the steady
      state levels of spindle alpha-tubulin by increasing the rate of microtubule
      polymerization. Overall, this study demonstrates a novel mechanism by which Gem
      contributes to the mitotic progression by maintaining correct spindle length
      through the kinesin Kif9.

PMID- 22964305
TI  - Mapping spatial approximations between the amino terminus of secretin and each of
      the extracellular loops of its receptor using cysteine trapping.
AB  - While it is evident that the carboxyl-terminal region of natural peptide ligands
      bind to the amino-terminal domain of class B GPCRs, how their biologically
      critical amino-terminal regions dock to the receptor is unclear. We utilize
      cysteine trapping to systematically explore spatial approximations among residues
      in the first five positions of secretin and in every position within the receptor
      extracellular loops (ECLs). Only Cys(2) and Cys(5) secretin analogues exhibited
      full activity and retained moderate binding affinity (IC(50): 92+/-4 and 83+/-1
      nM, respectively). When these peptides probed 61 human secretin receptor cysteine
      replacement mutants, a broad network of receptor residues could form disulfide
      bonds consistent with a dynamic ligand-receptor interface. Two distinct patterns
      of disulfide bond formation were observed: Cys(2) predominantly labeled residues
      in the amino terminus of ECL2 and ECL3 (relative labeling intensity: Ser(340),
      94+/-7%; Pro(341), 84+/-9%; Phe(258), 73+/-5%; Trp(274) 62+/-8%), and Cys(5)
      labeled those in the carboxyl terminus of ECL2 and ECL3 (Gln(348), 100%;
      Ile(347), 73+/-12%; Glu(342), 59+/-10%; Phe(351), 58+/-11%). These constraints
      were utilized in molecular modeling, providing improved understanding of the
      structure of the transmembrane bundle and interconnecting loops, the orientation
      between receptor domains, and the molecular basis of ligand docking. Key spatial
      approximations between peptide and receptor predicted by this model (H(1)-W(274),
      D(3)-N(268), G(4)-F(258)) were supported by mutagenesis and residue-residue
      complementation studies.

PMID- 22964306
TI  - CO2 permeability of cell membranes is regulated by membrane cholesterol and
      protein gas channels.
AB  - Recent observations that some membrane proteins act as gas channels seem
      surprising in view of the classical concept that membranes generally are highly
      permeable to gases. Here, we study the gas permeability of membranes for the case
      of CO(2), using a previously established mass spectrometric technique. We first
      show that biological membranes lacking protein gas channels but containing normal
      amounts of cholesterol (30-50 mol% of total lipid), e.g., MDCK and tsA201 cells,
      in fact possess an unexpectedly low CO(2) permeability (P(CO2)) of ~0.01 cm/s,
      which is 2 orders of magnitude lower than the P(CO2) of pure planar phospholipid
      bilayers (~1 cm/s). Phospholipid vesicles enriched with similar amounts of
      cholesterol also exhibit P(CO2) ~ 0.01 cm/s, identifying cholesterol as the major
      determinant of membrane P(CO2). This is confirmed by the demonstration that MDCK
      cells depleted of or enriched with membrane cholesterol show dramatic increases
      or decreases in P(CO2), respectively. We demonstrate, furthermore, that
      reconstitution of human AQP-1 into cholesterol-containing vesicles, as well as
      expression of human AQP-1 in MDCK cells, leads to drastic increases in P(CO2),
      indicating that gas channels are of high functional significance for gas transfer
      across membranes of low intrinsic gas permeability.

PMID- 22964308
TI  - Colon metastasis of chromophobe renal cell carcinoma with sarcomatoid change.
AB  - We present a rare case of colonic metastasis of renal cell carcinoma (RCC) and
      review the literature. A 54-year-old male was referred to our hospital with a
      history of bloody stools and fever. A right kidney tumor measuring about 10 cm in
      diameter was found by abdominal computed tomography. Right radical nephrectomy
      and a right hemicolectomy with ileotransversostomy were performed. Pathological
      diagnosis was chromophobe RCC with sarcomotoid change involving the colon.
      Chromophobe RCC with sarcomotoid change is very rare.

PMID- 22964307
TI  - Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia.
AB  - High temperature requirement A (HtrA) family proteins are serine proteases that
      may serve in the quality control of misfolded or mislocalized proteins. Recently,
      possible involvements of HtrA1 in the normal development of the placenta and in
      the pathogenesis of pre-eclampsia were reported. In this study, we characterized
      HtrA4, a previously uncharacterized HtrA protein family member, in pre-eclampsia.
      Elevated expression levels of placental HtrA4 in pre-eclampsia patients were
      observed by qRT-PCR. Western blotting also showed an increased production of
      HtrA4 at the protein level in pre-eclamptic placentas. In normal chorionic villi,
      HtrA4 protein was more abundant in the cytoplasm of cytotrophoblasts than in
      syncytiotrophoblasts. In contrast, the amount of HtrA4 protein in
      syncytiotrophoblasts was dramatically increased in pre-eclamptic placentas.
      Circulating HtrA4 was detected at higher levels in sera from women with pre
      eclampsia than from those with normotensive pregnancies. Serum HtrA4 levels were
      higher in patients with early onset and inversely correlated with the weights of
      the newborn and placenta. Furthermore, serum levels correlated with serum PAPP-A
      and PAPP-A2 levels, indicating a functional role for HtrA4 in the common pathway.
      These data suggest that increased HtrA4 may be involved in the onset of pre
      eclampsia, and elevated levels in sera imply a potential application as a
      biomarker for this disorder.

PMID- 22964309
TI  - Electrophysiological, pathological, and molecular study in diagnosis of
      neuromuscular disease.

PMID- 22964310
TI  - Serum antibodies to 25 myelin oligodendrocyte glycoprotein epitopes in multiple
      sclerosis and neuromyelitis optica: clinical value for diagnosis and disease
      activity.
AB  - BACKGROUND: Whether antibody to myelin oligodendrocyte glycoprotein (MOG) can be
      a diagnostic marker for multiple sclerosis (MS) is still controversial. Recent
      studies suggested that serum specific anti-MOG epitope antibody might be an MS
      specific marker. However, these studies did not include neuromyelitis optica
      (NMO) which might be proven to also have anti-MOG antibody. Hence, the present
      study was undertaken to investigate the clinical value of serum antibodies to 25
      MOG epitopes in conventional MS (CMS) and NMO. METHODS: Serum anti-MOG epitope
      IgG was detected in 61 CMS patients, 54 NMO patients, and 77 healthy controls,
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: Anti-MOG(27-38) IgG
      levels in both CMS and NMO patients were significantly higher than that in
      healthy controls (optical density (OD): 0.64 +/- 0.38, 0.48 +/- 0.23 vs. 0.19 +/-
      0.09; P = 0.000). CMS and NMO patients in relapse stage had significantly higher
      anti-MOG(27-38) IgG level than patients in remission stage (OD: 0.55 +/- 0.14 vs.
      0.24 +/- 0.09, P = 0.027). CONCLUSION: Although serum anti-MOG epitope IgG could
      not differentiate MS from NMO, it may be a useful marker for monitoring disease
      activity.

PMID- 22964311
TI  - A pilot study on the relationship between thyroid status and neuropsychiatric
      symptoms in patients with Alzheimer disease.
AB  - BACKGROUND: Growing evidence links alternation of the thyroid function to the
      pathogenesis and progression of Alzheimer disease (AD). However, only a few
      studies evaluate the association between thyroid hormone levels and
      neuropsychiatric manifestations in patients with AD. This study aimed to
      investigate the relationship of thyroid hormone levels and neuropsychiatric
      symptoms in euthyroid patients with AD. METHODS: Forty patients with AD (26 women
      and 14 men), with no prior AD treatment within 4 weeks before study entry, were
      evaluated on their thyroid status (total triiodothyronine (TT3), total thyroxine
      (TT4), and thyroid-stimulating hormone (TSH)), cognition (Mini-Mental State
      Examination (MMSE) and Alzheimer's disease Assessment Scale-Cognitive Subscale
      (ADAS-cog)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)) and
      depression (Hamilton Rating Scale for Depression (HAMD(17))). The unique
      relationship between thyroid hormones and cognitive function and mood was
      examined with multivariate linear regression analyses. The thyroid status between
      the neuropsychiatric symptoms group and the non-neuropsychiatric symptoms group
      was examined with independent-samples t-test. RESULTS: In euthyroid AD patients
      with agitation and irritability has lower TSH serum level than those without
      these symptoms (t = -2.130, P < 0.05; t = -2.657, P < 0.05); and core score of
      HAMD is significantly associated with the serum level of TSH (beta = 0.395, P <
      0.01). There is no significant association between thyroid hormone levels and
      cognition (MMSE, ADAS-cog and its subscale score). CONCLUSION: There might be a
      relationship between thyroid hormone levels and the neuropsychiatric symptoms in
      euthyroid patients with AD.

PMID- 22964312
TI  - Study on hippocampal volume with quantitative 3T magnetic resonance imaging in
      Chinese patients with epilepsy.
AB  - BACKGROUND: It was still rare for the quantitative magnetic resonance imaging
      (MRI) research of regional changes in hippocampus sclerosis (HS) in Chinese
      patients with epilepsy. This study aimed to study the hippocampal volumes (HVs)
      with quantitative MRI measurement in Chinese patients with epilepsy. METHODS:
      Forty-six Chinese patients with epilepsy (intractable epilepsy (IE), n = 21; non
      intractable epilepsy (NIE), n = 25) and 25 normal controls were collected between
      July 2007 and March 2008. All of the subjects underwent a 3T high-resolution MRI
      with oblique coronal thin sections oriented perpendicular to the hippocampal long
      axis. Hippocampal structures were assessed by visual detection, and HVs were
      quantitatively studied with a Picture Archiving and Communication System (PACS).
      RESULTS: Our study suggested that there was no significant difference in gender
      (P > 0.05) while the right hippocampal head volume (HHV), hippocampal body volume
      (HBV), and the whole hippocampal volume (HCV) were greater than the left one (P <
      0.05), but no significant difference was found in bilateral hippocampal tail
      volume (HTV) (P > 0.05) in normal controls. That unilateral/diffuse (64%/21%) and
      bilateral/focal (86%/20%) hippocampal atrophy (HA) were significant in IE and NIE
      patients, respectively. Anterior hippocampus, especially HHV (26% in IE and 20%
      in NIE) and HBV (29% in IE and 12% in NIE), had more significant atrophy than the
      HTV (5% in IE and 0% in NIE) in patients with epilepsy. CONCLUSION: By assessing
      the volumes of the regional hippocampus with 3T MRI, we could better define the
      range and distribution of HS, since regional or subtle changes in HVs could be
      detected earlier with 3T MRI.

PMID- 22964313
TI  - Clinical significance of pain in patients with chronic heart failure.
AB  - BACKGROUND: There is a paucity of studies investigating the clinical and
      biochemical characteristics of pain in chronic heart failure (CHF) patients. This
      study aimed to determine the clinical and biochemical characteristics and
      outcomes in Chinese patients with CHF and symptoms of pain. METHODS:
      Sociodemographics, serum levels of creatinine, NT-proBNP, high-sensitivity C
      reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6
      and IL-10, and two-dimensional echocardiographic left ventricular ejection
      fraction (LVEF) were determined in 305 patients with CHF. A questionnaire packet
      including the Brief Pain Inventory (BPI) and the Minnesota Living with Heart
      Failure Questionnaire (MLHFQ) was used to assess the degree of pain rated on a 0 
      10 scale and the quality of life (QOL). A six-minute walking test was performed
      during routine clinic visits. Major adverse cardiac events (MACE) were recorded;
      including all-cause or cardiac mortality and rehospitalization because of
      myocardial infarction, worsening heart failure or stroke at follow-up. RESULTS:
      Pain occurred in 25.6% of CHF patients, and was more common when the New York
      Heart Association (NYHA) functional class was worse. More patients with pain were
      female in gender, and had more co-morbidities, lower LVEF, and shorter distance
      during the 6-minute walking test. Despite similar serum levels of creatinine, N
      terminal prohormone of brain natriuretic peptide (NT-proBNP), IL-6 and IL-10, the
      TNF-alpha levels were higher and MLHFQ scores were greater in CHF patients with
      pain. At follow-up, CHF patients with moderate to severe pain (>= 4 scale) had
      higher rates of all-cause and cardiac mortality and rehospitalization because of
      myocardial infarction, worsening heart failure or stroke. Multivariate regression
      analysis revealed that the presence of pain was an independent risk factor for
      MACE and reduced QOL in CHF patients. CONCLUSIONS: Pain occurs in all stages of
      the CHF trajectory, and its incidence increases as clinical functional status is
      worsened. The presence of pain exerts a negative impact on clinical outcome and
      QOL in patients with CHF.

PMID- 22964314
TI  - Off-pump anteroapical aneurysm plication for left ventricular post-infarction
      aneurysm: long-term results.
AB  - BACKGROUND: The temporal response to off-pump anteroapical aneurysm plication has
      not been well defined. We have evaluated the long-term clinical and functional
      results of this technique and compared the efficacy with the patch modeling
      repair. METHODS: From March 2005 to May 2010, 163 (115 men and 48 women)
      consecutive patients were operated on for post-infarction left ventricular
      aneurysm (LVA), 54 patients underwent patch remodeling (group A) and 109 patients
      underwent off-pump anteroapical aneurysm plication repair (group B). All patients
      had simultaneous coronary revascularization, other operative procedures included
      septoplasty in eight and ablation of ventricular tachycardia in six. Follow-up
      ranged from 1 to 5 years, short-term and mid-term outcomes, including
      complications, cardiac function, and mortality, were assessed. RESULTS: Early
      mortality was 1.8% for all patients (group A 1 death vs. group B 2 deaths, not
      significant (NS)). Peri-operative support included intraaortic balloon pumping in
      16 (9.8%), (group A 6 patients vs. group B 10 patients, NS) and inotropic drugs
      in 84 (51.5%), (group A 34 vs. group B 50, NS). During a mean follow-up of (3.7+/
      0.8) years, eight patients died, with four due to cardiac-related causes. No
      patient required transplantation, and two required use of an implantable
      cardioverter-defibrillator for ventricular tachycardia. Survival at 1 and 5 years
      was 95% and 86%, respectively. It did not differ significantly between group A
      and group B. Functional class improved from 2.90 +/- 0.59 to 1.65 +/- 0.54 among
      the mid-term survivors (P < 0.001), with no significant difference between the
      two groups. Pre-operative risk factors for mortality or poor function were
      ejection fraction (EF) < 0.35 (OR = 7.9, 95%CI 1.6 - 40.0); congestive heart
      failure (CHF) (OR = 4.4, 95%CI 1.0 - 19.0); end-systolic volume index (ESVI) > 80
      ml/m(2) (OR = 3.7, 95%CI 1.0 - 14.0); and advanced age > 70 years (OR = 2.4,
      95%CI 1.0 - 12.0). CONCLUSIONS: The technique of off-pump anteroapical aneurysm
      plication associated with coronary grafting can be performed with low operative
      mortality, providing good symptomatic relief and long-term survival, and similar
      results can be achieved with patch modeling repair.

PMID- 22964315
TI  - Transesophageal echocardiography guided cannulation for peripheral
      cardiopulmonary bypass during robotic cardiac surgery.
AB  - BACKGROUND: Minimally invasive cardiac surgery and closed chest cardiopulmonary
      bypass (CPB) techniques continue to evolve. Previous reports have demonstrated
      the benefits of fluoroscopy guided cannulation for endovascular CPB during port
      access cardiac surgery. However, few data are available on the role of
      transesophageal echocardiography (TEE) guided cannulation for peripheral CPB
      during robotic cardiac surgery. The purpose of this study was to evaluate TEE
      guided cannulation for peripheral CPB during robotic cardiac surgery. METHODS: We
      performed a retrospective analysis of intraoperative data of 129 consecutive
      patients underwent robotic cardiac surgical procedures requiring peripheral CPB
      from September 2007 to August 2011, which was established using femoral arterial
      inflow and kinetic venous drainage by way of the femoral vein and right internal
      jugular vein and a transthoracic aortic cross clamp. TEE was used to guide
      cannulation of the inferior vena cava (IVC), superior vena cava (SVC), and
      ascending aorta (AAO). The success rate and the complication rate of TEE guided
      cannulation for peripheral CPB were evaluated and compared with the results of
      fluoroscopy guided cannulation in a historical control group. RESULTS: One
      hundred and twenty-nine consecutive patients underwent robotic cardiac surgical
      procedures requiring peripheral CPB. There were 67 female (51.9%) and 62 male
      (48.1%) patients, ranging in age from 13 to 70 years (mean (43.94 +/- 13.82)
      years) and body surface area 1.32 to 2.39 m(2) (mean (1.71 +/- 0.20) m(2)). Some
      61 (47.3%) patients underwent mitral valve repair, 27 (20.9%) mitral valve
      replacement, 27 (20.9%) left atrial myxoma removal, and 14 (10.9%) ventricular
      septal defect repair. Of the 129 patients, TEE guided cannulation of the IVC or
      SVC was successful in all patients (100%), and no puncture related complications
      occurred in all patients. Of the 129 patients, successful cannulation of the AAO
      was achieved in all patients (100%), and aortic perforation occurred in 1 patient
      (0.78%) under TEE guidance. Of the 42 patients in the historical control group,
      successful cannulation occurred in 39 patients (92.86%), and major complications
      occurred in 3 patients (7.14%) under fluoroscopy guidance. TEE guided cannulation
      of the AAO significantly improved success rate (100% vs. 92.86%, P = 0.014) and
      decreased complication rate (0.78% vs. 7.14%, P = 0.046). CONCLUSION: TEE may be
      useful in guiding successful placement of the cannulae in the IVC, SVC, and AAO
      in the establishment of peripheral CPB during robotic cardiac surgery.

PMID- 22964316
TI  - Intravenous injection of nicardipine changed the distribution of coronary artery
      endothelial shear stress and fluid dynamics in patients with unstable angina.
AB  - BACKGROUND: Coronary endothelial shear stress (ESS) triggered the development of
      atherosclerosis. However, the effect of calcium channel antagonist on the
      distribution of ESS remained unclear. METHODS: Twenty consecutive patients with
      acute coronary syndrome (ACS) 48 hours after maximal medication with single left
      anterior descending artery stenosis < 50% were studied. Nicardipine was
      intravenously injected at 1 ug/kg after a bolus of 10 mg in order to achieve mean
      blood pressure (MBP) reduced by 10% or more, or the heart rate increased by 10 -
      15 beats/min. Hemodynamic variables and angiogram at baseline and during
      injection of nicardipine were recorded, respectively. Coronary artery 3-D
      reconstruction was used for the analysis of ESS. RESULTS: Distal reference-vessel
      diameter and minimal lumen diameter decreased significantly from (2.42 +/- 0.41)
      mm and (1.47 +/- 0.49) mm at baseline to (2.22 +/- 0.35) mm and (1.35 +/- 0.49)
      mm at maximal drug-dosage (P = 0.018 and 0.020, respectively). Nicardipine did
      not change blood velocity. Lowest mean shear stress at segments 2-mm distal to
      plaque increased significantly from (0.034 +/- 0.519) Pa at baseline to (0.603 +/
      0.728) Pa (P = 0.013) at peak effect of drug. CONCLUSIONS: Nicardipine was
      associated with the constriction of diseased vessel segment that adapted to the
      reduction of blood pressure, without dynamic change of blood velocity at each
      stage of whole cardiac cycle. Increased ESS value at segments distal to plaque
      reflected the cardioprotection by nicardipine (ChiCTR-TRC-10000964).

PMID- 22964317
TI  - Transduction of mesenchymal stem cells with multidrug resistance gene provides
      protection for bone marrow toxicity after being transplanted into a nude mice
      model.
AB  - BACKGROUND: Myelosuppression is the main dose-related toxicity of many
      chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well-known
      for its ability to confering drug resistance. In this study, we meant to
      transplant the placenta mesenchymal stem cells (P-MSCs) moderated by mdr1 gene
      into a nude mice model radiated by gamma-Co(60) and to explore the
      chemoprotection for bone marrow (BM) toxicity. METHODS: Human P-MSCs were
      isolated from trypsin-digested term placentas and then transduced by with
      reconstructed retroviral vector containing mdr1 gene and green fluorescent
      protein (GFP) reporter gene. The integration and expression of mdr1 gene was
      observed indirectedly by the expression of GFP. A nude mice model was constructed
      after irradiation with a sublethal dosage of gamma-Co(60). These irradiated mice
      were transplanted with mdr1-MSCs through the caudal vein and then received
      paclitaxel (PAC) intraperitoneal chemotherapy. The Peripheral peripheral blood
      (PB) of the nude mice was collected, and the PB cells counts and values were
      determined using an automatic analyzer. RESULTS: After PAC treatment, mdr1-MSCs
      transplanted mice showed markedly improved survival upon compared to MSCs
      transplanted mice (85.7% vs. 57.1%). White blood cell (WBC) and red blood cell
      (RBC) counts as well as the hemoglobin (Hb) values were significantly increased
      in PAC treated mdr1-MSCs mice compared to PAC treated control mice when PAC
      chemotherapy had been finished (all P < 0.05), but the difference was not found
      in the plateltes (PLT) count (P > 0.05). CONCLUSION: Human P-MSCs moderated by
      mdr1 gene when transplanted into nude mice may provide chemoprotection for
      hematopoietic toxicity.

PMID- 22964318
TI  - Molecular basis of weak D and DEL in Han population in Anhui Province, China.
AB  - BACKGROUND: Rh blood group system is the most complex and immunogenetic blood
      group system. Prevalent RHD alleles varied in different populations. The purpose
      of this study is to determine the molecular basis of weak D and DEL phenotype in
      Anhui Chinese Han population. METHODS: The D antigen was determined with IgM
      monoclonal anti-D conformed to the guidelines for donor testing in China. Weak D
      samples were identified by an indirect antiglobulin test. DEL phenotype was
      determined by adsorption and elution test. All the RHD 10 exons were screened by
      PCR with sequence-specific priming or sequenced for the first-time donors who
      typed weak D, DEL or D negative by serologic test. RESULTS: Of all the 30 799
      blood donors, 155 blood samples were found D negative with IgM anti-D; 34 blood
      samples were found D positive by indirect antiglobulin test or absorption elution
      test. RHD alleles were identified by nucleotide sequencing. Total 4 RHD alleles
      were found including two new. One hundred and twenty of 155 (77.4%) of the
      serologically D negative samples lacked the RHD gene. One D negative was
      RHD(615del2). Thirty-two of 155 (20.6%) carried RHD(K409K) among them one
      carrying 1227G > A and 845G > A. Two of 155 (1.3%) was weak D type 15.
      CONCLUSIONS: In this study at the molecular level, all DEL phenotype is
      RHD(K409K); weak D type 15 is the prevalent weak D allele in Anhui Chinese Han
      population. Additionally, an improved more efficient method was adopted to
      amplify all the RHD exons in one PCR program. Our study added to the
      understanding of molecular mechanisms underlying D antigen expression in Anhui
      Han population and provided useful information for adopting suitable genotyping
      strategies in routine use.

PMID- 22964319
TI  - Comparison between peritoneal tuberculosis and primary peritoneal carcinoma: a 16
      year, single-center experience.
AB  - BACKGROUND: Peritoneal tuberculosis and primary peritoneal carcinoma can both
      present as an abdominal mass and ascites with elevated serum CA125. The purpose
      of our study was to evaluate the clinical features of peritoneal tuberculosis,
      compare them with features of primary peritoneal carcinoma, and establish
      definitive diagnostic procedures. METHODS: We conducted a retrospective study in
      patients with peritoneal tuberculosis from January 1995 to October 2010 at Peking
      Union Medical College Hospital. During this time, the data of 38 patients with
      primary peritoneal carcinoma were reviewed. RESULTS: The median age was 34 years
      (range, 19 - 80 years). The most common symptoms were abdominal distension
      (16/30, 53.3%) and an abdominal mass (12/30, 40.0%). The serum CA125 level was
      elevated in 25 patients (83.3%). The median level of cancer antigen CA125 was
      392.5 U/ml (range, 0.6 - 850.0 U/ml). Abdominal ultrasound revealed a pelvic mass
      in 25 patients and ascites in 20 patients. Diagnostic laparoscopy was performed
      in 15 patients (50.0%) and exploratory laparotomy was performed in 12 patients
      (40.0%), and 3 patients (10.0%) who underwent laparoscopy converted to laparotomy
      because of severe adhesions. The intraoperative findings were adhesions, multiple
      white tubercles, and ascites. Frozen tissue sections were obtained in 17
      patients, and 14 of whom showed chronic granulomatous reactions. Final
      pathological examinations confirmed the diagnosis. CONCLUSIONS: Peritoneal
      tuberculosis should be considered as a differential diagnosis, especially for
      young women with an abdominal mass, ascites, and elevated serum CA125 levels.
      Laparoscopy is a useful diagnostic method for peritoneal tuberculosis, and
      intraoperative frozen sections are recommended when the diagnosis is in doubt.

PMID- 22964320
TI  - Fast track surgery accelerates the recovery of postoperative insulin sensitivity.
AB  - BACKGROUND: Few clinical studies or randomized clinical trial results have
      reported the impact of fast track surgery on postoperative insulin sensitivity.
      This study aimed to investigate the effects of fast track surgery on
      postoperative insulin sensitivity in patients undergoing elective open colorectal
      resection. METHODS: Controlled, randomized clinical trial was conducted from
      November 2008 to January 2009 with one-month post-discharge follow-up. Seventy
      patients with colorectal carcinoma requiring colorectal resection were randomized
      into two groups: a fast track group (35 cases) and a conventional care group (35
      cases). All included patients received elective open colorectal resection with
      combined tracheal intubation and general anesthesia. Clinical parameters
      (complication rates, return of gastrointestinal function and postoperative length
      of stay), stress index and insulin sensitivity were evaluated in both groups
      perioperatively. RESULTS: Sixty-two patients finally completed the study, 32
      cases in the fast-track group and 30 cases in the conventional care group. Our
      findings revealed a significantly faster recovery of postoperative insulin
      sensitivity on postoperative day 7 in the fast-track group than that in the
      conventional care group. We also found a significantly shorter length of
      postoperative stay and a significantly faster return of gastrointestinal function
      in patients undergoing fast-track rehabilitation. CONCLUSION: Fast track surgery
      accelerates the recovery of postoperative insulin sensitivity in elective surgery
      for colorectal carcinoma with a shorter length of postoperative hospital stay.

PMID- 22964321
TI  - Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1
      cytokines and reduces HBsAg level in transgenic mice.
AB  - BACKGROUND: The Fc receptor associated pathway might improve the immune responses
      against hepatitis B virus (HBV) as previously described by us. In addition, the
      Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo
      and may act as a potential adjuvant to boost antigen-specific immune responses.
      In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc
      and/or FL were evaluated in HBsAg transgenic mice. METHODS: The fusion proteins
      composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3
      ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize
      HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti
      HBsAg and cytokine profile, and the activities of alanine aminotransferase
      (ALT)/AST were investigated after immunization. RESULTS: After six injections,
      the most pronounced decrease in serum and liver HBsAg levels was observed in the
      HBsAg-Fc immunized group. In addition, serum Th1 cytokines and ALT/AST activities
      were highest in this group, indicating an effective induction of a favorable
      cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc
      and the Flt3 ligand stimulated an alternative Th1-type immune response featured
      with high level productions of tumor necrosis factor alpha (TNF-alpha) and
      monocyte chemoabstractant protein 1 (MCP-1), causing a more severe cytotoxicity
      in hepatocytes while showed less effective in reducing serum HBsAg level.
      CONCLUSION: HBsAg-Fc is effective in eliciting both the humoral and cellular
      immune responses against HBsAg in HBsAg transgenic mice, which makes it a
      potential immunogen for the immunotherapy of chronic hepatitis B.

PMID- 22964322
TI  - Histone deacetylase inhibitors inducing human cervical cancer cell apoptosis by
      decreasing DNA-methyltransferase 3B.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors are a group of small chemical
      molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have
      multiple biological effects such as cell cycle arrest, apoptosis, cell
      differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone
      and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely
      used in cancer therapy because of its function of inducing apoptosis. However,
      the mechanisms of apoptosis effect are not fully understood. TSA is a classical
      HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this
      study, we selected Trichostatin A (TSA) to investigate the mechanisms of HDAC
      inhibitors apoptotic effect on cancer cells. METHODS: Cervical cancer cell lines
      such as Hela, Caski and normal human keratinocyte line HaCaT were treated with
      various concentrations of TSA. Crystal violent assay and 3-(4,5-Dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine cell
      number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA
      methyltransferase (DNMT)1, DNMT3A and DNMT3B were determined by regular PCR, qPCR
      and Western Blotting. Small interfering RNA (SiRNAi) was used to knock down
      DNMT3B. RESULTS: HDAC inhibitors only induce cervical cancer cell apoptosis. At 1
      umol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal
      cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, (90.0 +/-
      8.4)% of normal cell survive after treated with 1 umol/L of TSA. We compared 1
      umol/L group with untreated control with t-test. There was no significance
      between 1 umol/L group and untreated control for normal cell (P > 0.05). HDAC
      inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock
      down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and
      Caski cell went apoptosis after deprived of DNMT3B. CONCLUSIONS: DNMT3B was
      essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC
      inhibitors may play an important role in the toxicity of HDAC inhibitors on
      cervical cancer cells.

PMID- 22964323
TI  - Expression of glycoprotein non-metastatic melanoma protein B in cutaneous
      malignant and benign lesions: a tissue microarray study.
AB  - BACKGROUND: Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an
      important role in the pathogenesis of inflammatory and malignant diseases. We
      investigated the expression of GPNMB in benign and malignant skin diseases.
      METHODS: Tissue microarray was performed in the skin tissues of 102 cases
      including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell
      carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues
      was detected by immunohistochemistry. Twenty cases of normal skin and adjacent
      neoplastic normal skin tissues were selected as controls. RESULTS: GPNMB was
      positively stained in skin malignancies (38/50, 76%), which was significantly
      higher than that in the control and the benign skin tissues (P = 0.001 and <
      0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC
      (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in
      patients aged >= 65 years than those less than 65 years (n = 11 and n = 9
      respectively, P = 0.027). No significant difference of the expression rates was
      observed between normal control and BCC; however, stronger intensity was detected
      in the latter. Negative or weak expression was observed in the controls.
      CONCLUSION: Over-expression of GPNMB correlated strongly and might play an
      important role in the pathogenesis of MM and SCC.

PMID- 22964324
TI  - Poland's syndrome in women: 24 cases study and literature review.
AB  - BACKGROUND: Since its first description in 1841, numerous variations and
      treatments of Poland's syndrome (congenital deficiency of the pectoralis major
      muscle associated with brachysyndactyly) have been reported. None of the reports,
      however, involved female Chinese patients. METHODS: A retrospective study of 24
      female patients was conducted to guide the selection of methods of surgical
      reconstruction. The patients were divided into three groups according to the
      degree of thoracic tissue development. Type I (mild): Limited tissue loss which
      can be treated with simple filling with autologous fat and/or an artificial
      breast implant. Type II (moderate): Moderate thoracic tissue hypoplasia where the
      breast parenchyma can still offer adequate implant coverage. Mammoplasty using a
      latissimus dorsi muscular flap with an implant was performed in this group. The
      flap was used to fill the infraclavicular hollow, and the implant was placed in
      the dual-plane pocket. Type III (severe): Severe thoracic tissue hypoplasia,
      without sufficient parenchyma to offer implant coverage. A latissimus dorsi
      muscular flap was used to form a total submuscular pocket in which an implant was
      placed. RESULTS: The numbers of Type I, II, and III patients were 15, 3, and 6,
      respectively. All of the flaps and injected fat demonstrated good survival.
      Satisfactory cosmetic results were exhibited during the follow-up period of 1 to
      9 years. CONCLUSIONS: Although this group of patients showed varied conditions,
      they can be roughly divided into three types according to the degree of thoracic
      tissue development. In our experience, this classification is simple and useful
      in choosing the breast reconstruction options.

PMID- 22964325
TI  - Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis.
AB  - BACKGROUND: Recent research shows that lasers can inhibit fungal growth and that
      Nd:YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of
      this study was to observe the effect of a long-pulse Nd:YAG 1064-nm laser on 154
      nails of 33 patients with clinically and mycologically proven onychomycosis.
      METHODS: Thirty-three patients with 154 nails affected by onychomycosis were
      randomly assigned to two groups, with the 154 nails divided into three sub-groups
      (II degree, III degree, and IV degree) according to the Scoring Clinical Index of
      Onychomycosis. The 15 patients (78 nails) in group 1 were given eight sessions
      with a one-week interval, and the 18 patients (76 nails) in group 2 were given
      four sessions with a one-week interval. RESULTS: In group 1, the effective rates
      at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the
      effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment
      effect was not significantly different between any sub-group pair (P > 0.05).
      CONCLUSIONS: Long pulse Nd:YAG 1064-nm laser was effective for onychomycosis. It
      is a simple and effective method without significant complications or side
      effects and is expected to become an alternative or replacement therapy for
      onychomycosis.

PMID- 22964326
TI  - Gene chip array for differentiation of mycobacterial species and detection of
      drug resistance.
AB  - BACKGROUND: Gene chip array can differentiate isolated mycobacterial strains
      using various mycobacterium specific probes simultaneously. Gene chip array can
      evaluate drug resistance to isoniazid and rifampin of tuberculosis strains by
      detecting drug resistance related gene mutation. This technique has great
      potential for clinical application. We performed a retrospective study to
      investigate the capability of gene chip array in the rapid differentiation of
      species and detection of drug resistance in mycobacterium, and to evaluate its
      clinical efficacy. METHODS: We selected 39 patients (54 clinical mycobacterium
      isolates), used gene chip array to identify the species of these isolates and
      detect drug resistance to isoniazid and rifampin in Mycobacterium tuberculosis
      isolates. Meanwhile, these patients' clinical data were analyzed retrospectively.
      RESULTS: Among these 39 patients whose mycobacterium culture were positive, 32
      patients' isolates were identified as Mycobacterium tuberculosis, all of them
      were clinical infection. Seven patients' isolates were identified as non
      tuberculosis mycobacterium. Analyzed with their clinical data, only two patients
      were considered as clinical infection, both of them were diagnosed as
      hematogenous disseminated Mycobacterium introcellulare infection. The other five
      patients' isolates were of no clinical significance; their clinical samples were
      all respiratory specimens. Clinical manifestations of tuberculosis and non
      tuberculous mycobacterial infections were similar. Isoniazid resistance was
      detected in two tuberculosis patients, while rifampin resistance was detected in
      one tuberculosis patient; there was another patient whose Mycobacterium
      tuberculosis isolate was resistant to both isoniazid and rifampin (belongs to
      multidrug resistance tuberculosis). The fact that this patient did not respond to
      routine anti-tuberculosis chemotherapy also confirmed this result. CONCLUSIONS:
      Gene chip array may be a simple, rapid, and reliable method for the
      identification of most mycobacterial species and detection of drug resistance in
      Mycobacterium tuberculosis. It is useful in diagnosis, treatment, and hospital
      infection control of mycobacterial infections, and it may have a great potential
      for clinical application.

PMID- 22964327
TI  - AMP-activated protein kinase acts as a negative regulator of high glucose-induced
      RANKL expression in human periodontal ligament cells.
AB  - BACKGROUND: It is well known that the function of periodontal ligament cells may
      be affected by high glucose levels. This study investigated the direct effect of
      high glucose on the expression of receptor activator of nuclear factor-kappa B
      ligand (RANKL) in human PDL (hPDL) cells. In addition, we examined whether this
      effect was mediated via AMPK activation. METHODS: We examined the expression of
      osteoprotegerin in hPDL cells cultured at different concentrations of glucose
      using real-time polymerase chain reaction (PCR), and Western blotting analysis.
      AMPK phosphorylation in hPDL cells was studied using immunoprecipitate kinase
      assay and Western blotting. The effect of AMPK activation on RANKL expression in
      hPDL cells was investigated by real-time PCR and Western blotting. RESULTS: High
      glucose levels caused an increase in RANKL mRNA and protein expression in hPDL
      cells. Moreover, the amount of p-AMPK and AMPK activity was lower in hPDL cells
      exposed to high glucose levels than in cells exposed to normal glucose levels.
      Suppression of AMPK by Compound C augmented RANKL expression, and AMPK activation
      by metformin significantly decreased RANKL expression in hPDL cells.
      Additionally, metformin down-regulated RANKL expression in hPDL cells exposed to
      high glucose via AMPK activation. CONCLUSION: High glucose-induced up-regulation
      of RANKL could be due to decreased AMPK activity, and AMPK activation may be
      involved in regulating of RANKL expression in hPDL cells.

PMID- 22964328
TI  - Tumor-associated macrophages: a novel potential target for cancer treatment.
AB  - Special emphasis about cancer metastasis was concentrated on tumor cells
      themselves, and we usually considered the ability of migration and invasion was
      the final decider. Recently, bewaring of tumor microenvironment is a fundamental
      determinant in metastasis has become the most outstanding breakthrough.
      Considerable "microbes" in the microenvironment are closely linked with tumor
      metastatic behaviors, and the major proportion of them is tumor-associated
      macrophages (TAMs). Actually, TAMs conserve immediate "cross-talk" with cancer
      cells throughout tumor development. It is generally accepted that TAMs have
      mostly pro-tumoral functions and play an important role in several stages of
      tumor progression. This progression involves a series of events that leads from
      the primary site to the metastatic site, including tumor cell growth,
      angiogenesis, migration, invasion, intravasation and finally extravasation at
      distant site where the process begins again (metastasis). Thereby, TAMs has
      attracted substantial attentions in recent years and could become a promising
      therapeutic strategy. In this review, we focus on the multi-functions of TAMs in
      cancer and certain drugs targeting TAMs for cancer treatment those are under
      experimental research procedures or have even been entered human clinical tests.

PMID- 22964329
TI  - Type 2 epithelial mesenchymal transition in vivo: truth or pitfalls?
AB  - Epithelial-mesenchymal transition (EMT) is a process by which fully
      differentiated epithelial cells undergo a phenotypic conversion and assume a
      mesenchymal cell phenotype, including elongated morphology, enhanced migratory
      and invasiveness capacity, and greatly increased production of extracellular
      matrix (ECM) components. The EMTs associated with wound healing, tissue
      regeneration, and organ fibrosis are termed as type 2 EMT. Over the past two
      decades, emerging evidence suggested that injured epithelial cells, via type 2
      EMT, may serve as important sources of fibroblasts and contribute to organ
      fibrosis, such as kidney, liver, lung and eyes. There is perhaps no doubt that
      adult epithelial cells can undergo EMT in vitro in response to transforming
      growth factor (TGF)-beta1 and other inflammatory or pro-fibrotic stimuli.
      However, whether type 2 EMT really occurs in vivo, whethers it is actually a
      source of functional and activated interstitial fibroblasts and whether it
      contributes to tissue fibrosis have already been the subjects of heated debate.
      In this review, we will describe the main features of EMT, the major findings of
      type 2 EMT in vitro, the evidences for and against type 2 EMT in vivo and discuss
      the heterogeneity and pitfalls of the techniques used to detect EMT during
      fibrotic diseases. We suggest that in order to ascertain the existence of type 2
      EMT in vivo, different proper phenotype markers of epithelial and mesenchymal
      cells should be jointly used and cell lineage tracking techniques should be
      standardized and avoid false positives. Finally, we believe that if EMT really
      occurs and contributes to tissue fibrosis, efforts should be made to block or
      reverse EMT to attenuate fibrotic process.

PMID- 22964330
TI  - Cardiac differentiation and electrophysiology characteristics of bone marrow
      mesenchymal stem cells.
AB  - OBJECTIVE: To review the progress of cardiac differentiation and
      electrophysiological characteristics of bone marrow mesenchymal stem cells. DATA
      SOURCES: The databases of PubMed, Springer Link, Science Direct and CNKI were
      retrieved for papers published from January 2000 to January 2012 with the key
      words of "bone marrow mesenchymal stem cells, cardiac or heart, electrophysiology
      or electrophysiological characteristics". STUDY SELECTION: The articles concerned
      cardiac differentiation and electrophysiological characteristics of bone marrow
      mesenchymal stem cells were collected. After excluding papers that study purposes
      are not coincident with this review or contents duplicated, 56 papers were
      internalized at last. RESULTS: For the treatment of myocardial infarction and
      myocardiac disease, the therapeutic effects of transplantation of bone marrow
      mesenchymal stem cells which have the ability to develop into functional
      myocardial cells by lots of methods have been proved by many researches. But the
      arrhythmogenic effect on ventricles after transplantation of bone marrow
      mesenchymal stem cells derived myocardial cells is still controversial in animal
      models. Certainly, the low differentiation efficiency and heterogeneous
      development of electrical function could be the most important risk for
      proarrhythmia. CONCLUSION: Many studies of cardiac differentiation of bone marrow
      mesenchymal stem cells have paid attention to improve the cardiac differentiation
      rate, and the electrophysiology characteristics of the differentiated cells
      should be concerned for the risk for proarrhythmia as well.

PMID- 22964331
TI  - Senescent remodeling of the immune system and its contribution to the
      predisposition of the elderly to infections.
AB  - OBJECTIVE: To review the senescent remodeling of the immune system with aging and
      its relevance to the increased susceptibility of the elderly to infectious
      diseases, along with an outlook on emerging immunological biomarkers. DATA
      SOURCES: The data selected were from PubMed with relevant published articles in
      English or French from 1995 to the present. Searches were made using the terms
      "immunosenescence" and "aging" paired with the following: "innate immunity", "T
      cell", "B-cell", "adaptive immunity" and "biomarkers". Articles were reviewed for
      additional citations and some information was gathered from web searches. STUDY
      SELECTION: Articles on aging of both the innate and adaptive immunity were
      reviewed, with special attention to the remodeling effect on the ability of the
      immune system to fight infectious diseases. Articles related to biomarkers of
      immunosenescence were selected with the goal of identifying immunological
      biomarkers predisposing the elderly to infections. RESULTS: Innate immunity is
      generally thought to be relatively well preserved or enhanced during aging
      compared with adaptive immunity which manifests more profound alterations.
      However, evidence, particularly in the last decade, reveals that both limbs of
      the immune system undergo profound remodeling with aging. Reported data on
      adaptive immunity is consistent and changes are well established but conflicting
      results about innate immunity were reported between in vivo and in vitro studies,
      as well as between murine and human studies. Epidemiological data suggests
      increased predisposition of the elderly to infections, but no compelling
      scientific evidence has directly linked senescent immune remodeling to this
      increased susceptibility. Recently, growing interest in identifying immunological
      biomarkers and defining "immune risk phenotypes/profiles" (IRP) has been
      expressed. Identification of biomarkers is in its early days and few potential
      biomarkers have been identified, with the Swedish having defined one IRP based on
      the adaptive immune response. CONCLUSIONS: Aging does not necessarily lead to an
      unavoidable decline in immune functions. Instead, a complex remodeling occurs.
      Despite the lack of compelling scientific evidence, senescent immune remodeling
      surely is a significant contributing factor to the increased risk and severity of
      infections in the elderly. Although, no immunological biomarker has been formally
      linked to the increased risk of infections in the elderly, biomarkers remain a
      promising tool to predict the likelihood of healthy aging, the level of immune
      competence, and mortality risk in the elderly. Hence, more research is required
      to define healthy aging and identify immunological biomarkers.

PMID- 22964332
TI  - Rho-associated coiled kinase inhibitor Y-27632 promotes neuronal-like
      differentiation of adult human adipose tissue-derived stem cells.
AB  - BACKGROUND: Y-27632 is a specific inhibitor of Rho-associated coiled kinase
      (ROCK) and has been shown to promote the survival and induce the differentiation
      of a variety of cells types. However, the effects of Y-27632 on adult human
      adipose tissue-derived stem cells (ADSCs) are unclear. This study aimed to
      investigate the effects of Y-27632 on the neuronal-like differentiation of ADSCs.
      METHODS: ADSCs were isolated from women undergoing plastic surgery and cultured.
      ADSCs were treated with different doses of Y-27632 and observed morphological
      changes under microscope. The expression of nestin, neuron specific enolase (NSE)
      and microtubule-associated protein-2 (MAP-2) in ADSCs treated with Y-27632 was
      detected by immunocytochemistry and Western blotting analysis. RESULTS: Y-27632
      had the potency to induce neuronal-like differentiation in ADSCs in a dose
      dependent manner. Moreover, the differentiation induced by Y-27632 was recovered
      upon drug withdraw. ADSCs treated with Y-27632 expressed neuronal markers such as
      NSE, MAP-2 and nestin while untreated ADSCs did not express these markers.
      CONCLUSION: Selective ROCK inhibitor Y-27632 could potentiate the neuronal-like
      differentiation of ADSCs, suggesting that Y-27632 could be utilized to induce the
      differentiation of ADSCs to neurons and facilitate the clinical application of
      ADSCs in tissue engineering.

PMID- 22964333
TI  - Identification of Max binding protein as a novel binding protein of Nck1 and
      characterization of its role in inhibiting human liver cancer SK-HEP-1 cells.
AB  - BACKGROUND: The tendency of tumor cells to disperse throughout the liver is a
      distinct feature of hepatocellular carcinoma (HCC). Nck family adaptor proteins
      function to regulate actin cytoskeletal reorganization that leads to cell
      motility. We previously found that Max binding protein (MNT) was differentially
      expressed in HCC, and interacted with Nck1 by 2-DE. MNT is a protein member of
      the Myc/Max/Mad network which plays roles in cell proliferation, differentiation,
      and death. We investigated the effects of MNT on migration of human liver cancer
      SK-HEP-1 cells to study the migration regulatory role of MNT in HCC cells.
      METHODS: Interaction between MNT and Nck1 was further validated in hepatoma cells
      by GST-pull down assay and immunoprecipitation. siRNAs specific to MNT (MNT
      siRNA) were used to knockdown MNT expression. Western blotting, transwell assay
      were used to determine the migration potential of cells. RESULTS: Interaction
      between MNT and Nck1 was validated in hepatoma cells. MNT knockdown promoted the
      migration of human liver cancer SK-HEP-1 cells (P < 0.01). CONCLUSION: The
      results suggest that MNT, via interaction with Nck1, inhibits hepatoma cell
      migration.

PMID- 22964334
TI  - Transradial artery intervention: an alternative approach for renal artery stent
      implantation?
AB  - BACKGROUND: Transfemoral artery access is the main approach for the
      interventional treatment of renal artery stenosis (RAS). This study aimed to
      investigate the technical feasibility of a transradial interventional (TRI)
      treatment of renal artery stenosis. METHODS: A series of 23 patients who
      underwent transradial renal artery stenting from October 2010 to October 2011
      were studied. Radial sheath system (Terumo, Japan) was used to get access to the
      radial artery. Radial tourniquet (Terumo) was used to stop bleeding. A 5Fr MPA
      (COOK, USA) was used to perform selective renal arteriography. Percutaneous renal
      artery stent systems were used to perform renal artery stenting. RESULTS: Renal
      artery angiography showed that 15 patients had unilateral renal artery stenosis
      and eight patients had bilateral renal artery stenosis. The descending aorta
      could not be catheterized in one patient because of the type III aortic arch.
      Twenty-two patients successfully underwent transradial renal artery angiography
      and the technical success rate was 95.7%. There was no puncture site hematoma or
      pseudoaneurysm. Mean procedure time was (38.4 +/- 7.2) minutes, the mean amount
      of contrast agent used was (93.2 +/- 6.3) ml, and the mean postprocedure bleeding
      time was (3.2 +/- 1.9) minutes. CONCLUSION: Transradial renal artery intervention
      is technically reliable with less invasion, rapid recovery, fewer complications
      and may become an alternative intervention approach for the treatment of renal
      artery stenosis.

PMID- 22964335
TI  - Bleb-associated endophthalmitis treated by sclera patch graft, vitrectomy and
      endoscopic cyclophotocoagulation.
AB  - BACKGROUND: Bleb-associated endophthalmitis (BAE) is a rare but severe
      complication of trabeculectomy with poor outcome. Various surgical methods were
      explored to treat such patients. However, there is no defined protocol. The aim
      of this study was to describe a new combined operation, and to demonstrate the
      outcome of the treatment. METHODS: Nine patients with BAE were enrolled in our
      study. The combined operation including pars plana vitrectomy (PPV), sclera patch
      graft (SPG) and endoscopic cyclophotocoagulation (ECP) was used to treat these
      patients. RESULTS: In the follow-up of 18 - 24 months, all patients with the
      endophthalmitis were cured, the useful visual acuity was preserved in 7 patients,
      and the intraocular pressure (IOP) of 8 patients was controlled just after first
      operation, only one needed another trans-scleral cyclophotocoagulation.
      CONCLUSION: This combined operation is a useful method for treating the patients
      with BAE, with SPG and vitrectomy to control the endophthalmitis and ECP to
      balance the postoperative IOP.

PMID- 22964336
TI  - Migraine-like headache and ischemic strokes in two patients with Lambl's
      excrescences.
AB  - Lambl's excrescences are filiform structures attached to the edges of cardiac
      valves and have been associated with stroke. Here we report two patients with
      Lambl's excrescences who developed migraine-like headaches followed by cerebral
      infarction. Their Lambl's excrescences were first identified by transesophageal
      echocardiography. One patient was given aspirin and another had surgery for
      debridement of excrescences. Their outcomes were good. The migraine-like headache
      might be the first symptom of cerebral ischemia and might be triggered by micro
      emboli originated from Lambl's excrescences. Patients with Lambl's excrescences
      should be closely monitored and surgery should be considered in recurrent stroke
      cases.

PMID- 22964337
TI  - Acute myocardial infarction after capecitabine treatment: not always vasospasm is
      responsible.
AB  - Capecitabine is an orally available chemotherapeutic agent that is converted to 5
      fluorouracil (5-FU) after absorbtion. Capecitabine and its active metabolite, 5
      FU, have cardiotoxic effects with reported instances of acute coronary syndromes
      caused due to coronary vasospasm. However, these agents exert toxic effects on
      cardiovascular system and beyond vasospasm provacation. We report a 46-year-old
      patient diagnosed as acute inferior infarction who is treated with capecitabine
      for 3 months due to metastatic breast carcinoma, in whom thrombotic coronary
      occlusion was observed in angiography. This case demonstrates that apart from
      vasospasm, coronary thrombosis could be observed after capecitabine treatment,
      with a possible direct effect of this drug.

PMID- 22964338
TI  - Ruptured azygos vein caused by blunt trauma on left chest.

PMID- 22964339
TI  - Neuroendocrine carcinoma in the auditory canal and middle ear.

PMID- 22964340
TI  - Pentalogy of Cantrell associated with a double-outlet right ventricle.

PMID- 22964341
TI  - Nebulized lidocaine in the treatment of intractable cough.
AB  - Cough is one of the most common symptoms prompting patients to be seen by health
      care providers in the United States. Persistent cough can disrupt daily
      activities such as conversation, eating, breathing, and sleeping, and it can
      become extremely debilitating both physically and mentally. Pharmacological
      treatments include dextramethorphan, opioid cough suppressants, benzonatate,
      inhaled ipratropium, and guaifenesin. Successful cough suppression has also been
      demonstrated in several studies with the use of nebulized lidocaine. Nebulized
      lidocaine also appears to be well tolerated by patients with minimal side effects
      including dysphonia, oropharyngeal numbness, and bitter taste. Studies conducted
      thus far have been small, so larger randomized control trials comparing nebulized
      lidocaine to placebo need to be conducted in the future. 

PMID- 22964342
TI  - Anticholinergics in palliative medicine: an update.
AB  - Anticholinergics, or antimuscarinic drugs, are drugs that competitively inhibit
      the action of acetylcholine at muscarinic receptors, leading to a blockade of the
      actions of the parasympathetic nervous system at sites where overactivity can
      lead to increased symptom burden. Successful blockade of the parasympathetic
      nervous system ultimately leads to decreased production of secretions in the
      salivary, bronchial, and gastrointestinal tracts. These effects are often used
      for several symptoms that originate due to parasympathetic nervous system
      overactivity, such as the "death rattle" and malignant bowel obstruction.
      Anticholinergic agents are divided into either tertiary amines or quaternary
      ammonium compounds, which differ in their ability to cross into the central
      nervous system. Quaternary compounds do not cross into the central nervous system
      and have a different adverse effect profile than the tertiary amines. The purpose
      of this review is to highlight anticholinergic agents, their pharmacology, and an
      evidence-based assessment of their role in palliative care. 

PMID- 22964343
TI  - Promoting sleep for hospitalized patients with advanced cancer with relaxation
      therapy: experience of a randomized study.
AB  - AIMS AND OBJECTIVES: Sleep disorders are frequent in patients with advanced
      cancer receiving palliative care. The objective of this study was to demonstrate
      whether relaxation therapy can improve their satisfaction with sleep. BACKGROUND:
      Few studies have investigated the effectiveness of relaxation in patients
      hospitalized with an advanced chronic disease. DESIGN: Prospective randomized
      study with an immediate intervention group (IIG; relaxation days 3-6) and a
      delayed intervention group (DIG; relaxation days 6-9). METHODS: The main measure
      was the overall satisfaction of sleep measured on a Numerical Rating Scale of
      Satisfaction of Sleep (NRSSS) between 0 and 10. RESULTS: Totally 18 (IIG: 9; DIG:
      9) patients were included in this study (mean age 66 +/- 10.7). The NRSSS
      improved in both the groups (almost statistically significant) between the day of
      inclusion and day 2. Because of the dropout of the patients during the last days
      of the study, we analyzed the improvement in sleep satisfaction only between day
      2 and 5. The NRSSS D5 for the immediate and delayed groups were 4.0 +/- 23 and
      3.8 +/- 2.3, respectively. There was no significant improvement in both the
      groups. CONCLUSION: The results demonstrated the difficulty to include patients
      with advanced cancer in a randomized study with a DIG. We were not able to
      demonstrate the effectiveness of relaxation therapy on sleep satisfaction.
      RELEVANCE TO CLINICAL PRACTICE: Techniques that can be easily used to improve
      sleep in patients with an advanced cancer should be developed and used already
      early in the disease.

PMID- 22964344
TI  - Clinical recovery of chronic intestinal pseudo-obstruction with cisapride in a
      complex pediatric patient.
AB  - Cisapride is a gastrointestinal prokinetic that facilitates or restores motility
      along the entire gastrointestinal tract. It has been used successfully to treat
      acute and chronic intestinal pseudo-obstructions (CIPs) in adults, but there is a
      paucity of literature surrounding the treatment of CIP in pediatric patients and
      therapies for CIP are limited and their impact is often unsatisfactory. This case
      report presents the use of cisapride in the management of pseudo-obstruction.
      Treatment with cisapride substantially improved the patient's symptoms and
      improved feeding tolerance. It improved his prognosis remarkably and prevented
      the need for end-of-life care. He experienced no adverse effects throughout the
      course of therapy. The treatment regimen is discussed in this case report.

PMID- 22964345
TI  - Switching the electronic properties of Co-octaethylporphyrin molecules on oxygen
      covered Ni films by NO adsorption.
AB  - Using x-ray absorption spectroscopy, we demonstrate that the electronic
      properties of Co-octaethylporphyrin (CoOEP) molecules on oxygen-covered ultrathin
      Ni films can be reversibly manipulated by a chemical stimulus. This is achieved
      by adsorption of nitrogen monoxide (NO), leading to the formation of a NO-CoOEP
      nitrosyl complex, and subsequent thermal desorption of the NO from the Co ions.
      The integration of the absorption spectra of the Co L(2,3) edges reveals a
      partial oxidation of the Co ions after dosing with NO compared to the pristine
      sample, for which a valency of 2+ and a low-spin state of the Co ions can be
      deduced from the Co L(2,3) XAS line shape. By means of x-ray magnetic circular
      dichroism the magnetic moments of the Co ions were found to be coupled parallel
      to the magnetization of the Ni films across the intermediate layer of atomic
      oxygen, before and after NO uptake.

PMID- 22964346
TI  - The sNIHSS-4 predicts outcome in right and left anterior circulation strokes.
AB  - BACKGROUND AND PURPOSE: Stroke severity measured by the National Institutes of
      Health Stroke Scale (NIHSS) is a strong predictor of functional outcome. A short
      version, the sNIHSS-5, scoring only strength in right and left leg, gaze, visual
      fields and language, was developed for use in the prehospital setting. Because
      scoring both legs in anterior circulation strokes is not contributive, we
      assessed the value of a 4-item score (the sNIHSS-4), omitting the item 'strength
      in the unaffected leg', in predicting stroke outcome. METHODS: The study
      population consisted of anterior circulation ischemic stroke patients who
      participated in the LUB-INT-9 trial. We included all patients in whom the
      following data were available: NIHSS within 6h after stroke onset and daily
      between days 2 and 5, and the 12-week modified Rankin Scale (mRS) score. Poor
      outcome was defined as a mRS score>3. RESULTS: There was an excellent correlation
      between the NIHSS and sNIHSS-4 at all time points for both left and right-sided
      strokes. Scores at day 2 were a good predictor of poor outcome. Cutoff scores for
      NIHSS and sNIHSS-4 at day 2 were 15 and 5 in left hemispheric strokes, and 12 and
      4 in right hemispheric strokes. CONCLUSION: The sNIHSS-4 is as good as the NIHSS
      at predicting stroke outcome in both right and left anterior circulation strokes.

PMID- 22964347
TI  - Gamma knife radiosurgery for lymphoplasmacyte-rich meningioma.

PMID- 22964348
TI  - Development and application of a method for the purification of free
      shigatoxigenic bacteriophage from environmental samples.
AB  - Shiga toxin producing Escherichia coli (STEC) strains are foodborne pathogens
      whose ability to produce Shiga toxin (Stx) is due to the integration of Stx
      encoding lambdoid bacteriophage (Stx phage). Circulating, infective Stx phages
      are very difficult to isolate, purify and propagate such that there is no
      information on their genetic composition and properties. Here we describe a novel
      approach that exploits the phage's ability to infect their host and form a
      lysogen, thus enabling purification of Stx phages by a series of sequential
      lysogen isolation and induction steps. A total of 15 Stx phages were rigorously
      purified from water samples in this way, classified by TEM and genotyped using a
      PCR-based multi-loci characterisation system. Each phage possessed only one
      variant of each target gene type, thus confirming its purity, with 9 of the 15
      phages possessing a short tail-spike gene and identified by TEM as Podoviridae.
      The remaining 6 phages possessed long tails, four of which appeared to be
      contractile in nature (Myoviridae) and two of which were morphologically very
      similar to bacteriophage lambda (Siphoviridae).

PMID- 22964349
TI  - Localized potentiation of sleep slow-wave activity induced by prefrontal
      repetitive transcranial magnetic stimulation in patients with a major depressive
      episode.
AB  - BACKGROUND: The effects of repetitive transcranial magnetic stimulation (rTMS) on
      sleep structure in major depression are currently unknown. OBJECTIVE: To
      determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in
      major depression. METHODS: In this open-label pilot study, twelve male patients
      with relatively mild depression, who had been medication-resistant, underwent 10
      daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC).
      Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline,
      Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session).
      Discrete Fourier Transform (DFT) band power analyses were performed to quantify
      delta and sigma band activities during Stages II-IV, and determine time courses
      of these activities between Baseline and Post-1 (first five sessions) and between
      Post-1 and Post-2 (last five sessions). RESULTS: Post-hoc tests based on a three
      way ANOVA model indicated significant delta power increase at F3 (t11 = -2.762, P
      = 0.018) during the first five sessions; however, sigma power was unchanged. No
      significant band power changes were observed during the second half. Stages II-IV
      (percent total sleep time) increased significantly during the first half (t12 = 
      2.43, P = 0.033). No other significant changes in sleep parameters or clinical
      correlations were observed. CONCLUSIONS: The first five sessions of high
      frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3,
      possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This
      increased activity was not observed during the last half, possibly due to a
      homeostatic regulation mechanism intrinsic to SWA.

PMID- 22964350
TI  - STM-switching of organic molecules on semiconductor surfaces: an above threshold
      density matrix model for 1,5 cyclooctadiene on Si(100).
AB  - The scanning tunnelling microscope (STM)-induced switching of a single
      cyclooctadiene molecule between two stable conformations chemisorbed on a Si(100)
      surface is investigated using an above threshold model including a neutral ground
      state and an ionic excited state potential. Switching was recently achieved
      experimentally with an STM operated at cryogenic temperatures (Nacci et al 2008
      Phys. Rev. B 77 121405(R)) and rationalized by a below threshold model using just
      a single potential energy surface (Nacci et al 2009 Nano Lett. 9 2997). In the
      present paper, we show that experimental key findings on the inelastic electron
      tunnelling (IET) switching can also be rationalized using an above threshold
      density matrix model, which includes, in addition to the neutral ground state
      potential, an anionic or cationic excited potential. We use one and two
      dimensional potential energy surfaces. Furthermore, the influence of two key
      parameters of the density matrix description, namely the electronic lifetime of
      the ionic resonance and the vibrational lifetimes, on the ground state potential
      are discussed.

PMID- 22964351
TI  - In vivo imaging of enteric neuronal networks in humans using confocal laser
      endomicroscopy.

PMID- 22964352
TI  - Coronary artery thromboembolism as a result of left ventricular sump aneurysm
      after congenital heart surgery.

PMID- 22964353
TI  - Single surgical procedure combining epicardial pacemaker implantation and
      subsequent extraction of the infected pacing system for pacemaker-dependent
      patients.
AB  - OBJECTIVES: Management of pacemaker infection in pacing-dependent patients is
      often challenging. Typically, temporary pacing is used while antibiotic therapy
      is given for a number of days before reimplantation of a new endocardial system.
      This results in a prolonged hospital stay and complications associated with
      temporary pacing. In this study, we examine the feasibility of performing a
      single combined procedure of epicardial pacemaker implantation followed by system
      extraction. METHODS: One hundred consecutive infected pacemaker-dependent
      patients underwent implantation of 2 epicardial ventricular leads and were
      converted to a ventricular demand pacing system. The infected pacing system was
      then extracted during the same procedure. Patients were followed up for 12
      months. RESULTS: Significant pericardial bleeding developed during the procedure
      in 3 patients. The presence of the pericardial drain positioned during the
      implantation of the epicardial pacing system meant that cardiac tamponade did not
      occur, allowing surgical repair with sternotomy to be carried out under stable
      hemodynamic conditions. Two of these 100 patients died in the 30-day
      postoperative period; 1 death was due to septic shock and 1 to pulmonary
      distress. Median 1-year epicardial pacing thresholds were stable and excellent
      (1.4 +/- 0.9 volts). However, 1 of the 2 leads developed increased thresholds in
      6 patients, which led to the exclusive use of other ventricular lead.
      CONCLUSIONS: A single combined procedure of surgical epicardial pacemaker
      implantation and pacemaker system extraction appears to be a safe and effective
      method for managing pacemaker-dependent patients with infected pacemakers.

PMID- 22964354
TI  - Discussion.

PMID- 22964355
TI  - Massage therapy for cardiac surgery patients--a randomized trial.
AB  - OBJECTIVES: To determine whether massage significantly reduces anxiety, pain, and
      muscular tension and enhances relaxation compared with an equivalent period of
      rest time after cardiac surgery. The feasibility of delivering the treatment,
      effects on heart rate, blood pressure, and respiratory rate, and patient
      satisfaction were also assessed. METHODS: Elective cardiac surgery patients were
      randomized to receive massage or rest time at 2 points after surgery. Visual
      analog scales were used to measure pain, anxiety, relaxation, muscular tension,
      and satisfaction. Heart rate, respiratory rate, and blood pressure were measured
      before and after treatment. Focus groups and feedback were used to collect
      qualitative data about clinical significance and feasibility. RESULTS: A total of
      152 patients (99% response rate) participated. Massage therapy produced a
      significantly greater reduction in pain (P = .001), anxiety (P < .0001), and
      muscular tension (P = .002) and increases in relaxation (P < .0001) and
      satisfaction (P = .016) compared to the rest time. No significant differences
      were seen for heart rate, respiratory rate, and blood pressure. Pain was
      significantly reduced after massage on day 3 or 4 (P < .0001) and day 5 or 6 (P =
      .003). The control group experienced no significant change at either time.
      Anxiety (P < .0001) and muscular tension (P < .0001) were also significantly
      reduced in the massage group at both points. Relaxation was significantly
      improved on day 3 or 4 for both groups (massage, P < .0001; rest time, P = .006),
      but only massage was effective on day 5 or 6 (P < .0001). Nurses and
      physiotherapists observed patient improvements and helped facilitate delivery of
      the treatment by the massage therapists on the ward. CONCLUSIONS: Massage therapy
      significantly reduced the pain, anxiety, and muscular tension and improves
      relaxation and satisfaction after cardiac surgery.

PMID- 22964356
TI  - Adenosine instead of supranormal potassium in cardioplegia: it is safe,
      efficient, and reduces the incidence of postoperative atrial fibrillation. A
      randomized clinical trial.
AB  - OBJECTIVE: We aimed to evaluate the efficacy and safety of a cold crystalloid
      cardioplegic solution with adenosine (1.2 mmol/L) instead of supranormal
      potassium. METHODS: Sixty low-risk patients scheduled for elective coronary
      artery bypass grafting (CABG) were randomized to receive standard cold
      crystalloid hyperkalemic cardioplegia (hyperkalemic group) or normokalemic
      cardioplegia in which supranormal potassium was replaced with 1.2 mmol/L
      adenosine (adenosine group). End points were postoperative release of troponin T
      and creatine kinase MB, hemodynamics measured by PiCCO arterial thermodilution
      catheters, perioperative release of markers of endothelial activation and injury,
      and clinical course. RESULTS: The adenosine group had a significantly shorter
      time to arrest than did the hyperkalemic group (mean +/- standard deviation, 11
      +/- 5 vs 44 +/- 18 seconds; P < .001). Three hearts in the adenosine group were
      probably not adequately drained and received additional hyperkalemic cardioplegia
      to maintain satisfactory cardioplegic arrest. There were no differences between
      groups with respect to perioperative release of markers of endothelial activation
      or injury and no differences between groups in postoperative release of troponin
      T or creatine kinase MB. Postoperative hemodynamics including cardiac index were
      similar between groups. The incidence of postoperative atrial fibrillation was
      significantly lower in the adenosine group than in the hyperkalemic group (4 vs
      15; P = .01). CONCLUSIONS: Adenosine instead of hyperkalemia in cold crystalloid
      cardioplegia is safe, gives more rapid cardiac arrest, and affords similar
      cardioprotection and maintenance of hemodynamic parameters, together with a
      marked reduction in the incidence of postoperative atrial fibrillation.

PMID- 22964358
TI  - Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with
      type 1 diabetes mellitus: a meta-analysis.
AB  - To evaluate the association between costimulatory molecule cytotoxic T-lymphocyte
      associated antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes
      mellitus(T1DM), sixty-three published studies before December, 2011 were
      included. Meta-analysis was performed for each genotype in a random/fixed effect
      model. The combined odds ratio (OR) with 95% confidence interval (95%CI) was
      calculated to estimate the strength of the association. Overall, significant
      correlation was noted between CTLA-4 gene polymorphism (i.e. +49A/G, CT60A/G in a
      per-allele model) and the risk of T1DM (for +49A/G: OR=1.47, 95%CI=1.36-1.60,
      P<0.001; for CT60A/G: OR=1.31, 95%CI=1.18-1.45, P<0.001). However, no significant
      association was noted between C(-318)T polymorphism and T1DM. In the subgroup
      analysis, for +49A/G and CT60A/G, the statistically significant associations were
      also demonstrated in diverse racial descents (Caucasian and Asian) and age of
      onset (<20 years and >20 years). In conclusion, our results suggest that CTLA-4
      polymorphism contributes to the susceptibility of T1DM.

PMID- 22964357
TI  - Unloading of right ventricle by bidirectional superior cavopulmonary anastomosis
      in hypoplastic left heart syndrome patients promotes remodeling of systemic right
      ventricle but does not improve tricuspid regurgitation.
AB  - OBJECTIVE: To evaluate the influence of volume unloading by bidirectional
      superior cavopulmonary anastomosis on the systemic right ventricle in patients
      with hypoplastic left heart syndrome. METHODS: A total of 90 consecutive patients
      with hypoplastic left heart syndrome, who had survived the early postoperative
      period after bidirectional superior cavopulmonary anastomosis, were studied.
      Seven patients were excluded because of tricuspid valve surgery before or in
      association with bidirectional superior cavopulmonary anastomosis. The
      echocardiograms of the remaining 83 patients were reevaluated for tricuspid valve
      regurgitation and the size of the tricuspid annulus before bidirectional superior
      cavopulmonary anastomosis and at the last available follow-up examination before
      total cavopulmonary connection. RESULTS: Echocardiograms were performed a median
      of 5 days before bidirectional superior cavopulmonary anastomosis. Tricuspid
      valve regurgitation was graded as 0 in 11 patients, I in 37 patients, II in 24
      patients, and III in 11 patients. Follow-up echocardiograms were performed a
      median of 17 months after bidirectional superior cavopulmonary anastomosis.
      Postoperatively, tricuspid valve regurgitation was graded as 0 in 14 patients, I
      in 37 patients, II in 21 patients, III in 6 patients, and IV in 5 patients.
      Postoperatively, the mean Z value of the tricuspid annulus stayed the same in
      patients with significant tricuspid valve regurgitation (grade III or IV) after
      bidirectional superior cavopulmonary anastomosis but had decreased in the
      remaining patients. No significant change was seen in the level of tricuspid
      valve regurgitation after bidirectional superior cavopulmonary anastomosis
      compared with the preoperative data. CONCLUSIONS: The relative size of the
      tricuspid annulus in patients with hypoplastic left heart syndrome decreases
      after bidirectional superior cavopulmonary anastomosis, most likely owing to
      volume unloading and promotion of the remodeling of the systemic right ventricle.
      However, this remodeling of the right ventricle does not improve the grade of
      tricuspid regurgitation.

PMID- 22964359
TI  - Mapping QTLs and candidate genes for iron and zinc concentrations in unpolished
      rice of Madhukar*Swarna RILs.
AB  - Identifying QTLs/genes for iron and zinc in rice grains can help in
      biofortification programs. 168 F(7) RILs derived from Madhukar*Swarna were used
      to map QTLs for iron and zinc concentrations in unpolished rice grains. Iron
      ranged from 0.2 to 224 ppm and zinc ranged from 0.4 to 104ppm. Genome wide
      mapping using 101 SSRs and 9 gene specific markers showed 5 QTLs on chromosomes
      1, 3, 5, 7 and 12 significantly linked to iron, zinc or both. In all, 14 QTLs
      were identified for these two traits. QTLs for iron were co-located with QTLs for
      zinc on chromosomes 7 and 12. In all, ten candidate genes known for iron and zinc
      homeostasis underlie 12 of the 14 QTLs. Another 6 candidate genes were close to
      QTLs on chromosomes 3, 5 and 7. Thus the high priority candidate genes for high
      Fe and Zn in seeds are OsYSL1 and OsMTP1 for iron, OsARD2, OsIRT1, OsNAS1, OsNAS2
      for zinc and OsNAS3, OsNRAMP1, Heavy metal ion transport and APRT for both iron
      and zinc together based on our genetic mapping studies as these genes strictly
      underlie QTLs. Several elite lines with high Fe, high Zn and both were
      identified.

PMID- 22964360
TI  - Need for clarification of data in the recent meta-analysis about TLR4
      polymorphisms and cancer risk.

PMID- 22964361
TI  - Racial and ethnic differences in depression by partner status and the presence of
      children in the household.
AB  - PURPOSE: Single motherhood is a well-established risk factor for depression in
      women. The goal of this study is to analyze the relationships among partner
      status, having children, and depression among women of White, Black, and Hispanic
      race/ethnicity. METHODS: Stratified analyses were conducted on 2002, 2003, 2005,
      2006, and 2008 cross-sectional survey data from 10,520 White women, 7,655 Black
      women, and 7,343 Hispanic women aged at least 18 years and residing in New York
      City. Depression was evaluated using Kessler's K6 scale. Race/ethnicity-specific
      logistic regression analysis assessed the association between partner status and
      depression among women with and without children. RESULTS: Partner status was
      significantly associated with depression among White (p < .0001) and Hispanic (p
      = .0001) women, but not among Black women (p = .82), after adjusting for age,
      nativity, employment, education, poverty level, general health, and health
      insurance. Among White women, the conditional odds of depression were elevated
      for single relative to partnered women both with (odds ratio [OR], 2.10; 95%
      confidence interval [CI], 1.57-2.81; p < .0001) and without (OR, 1.29; 95% CI,
      1.06-1.56; p = .01) children, but the size of the effect was significantly larger
      for those with children than for those without children (p = .006). Among
      Hispanic women, the conditional odds of depression were elevated for single
      relative to partnered women with children (OR, 1.58; 95% CI, 1.29-1.95; p <
      .0001), but not for single versus partnered women without children (OR, 1.09; 95%
      CI, 0.82-1.46; p = .54). Among Black women, there was no evidence of elevated
      depression in single relative to partnered women, either overall or conditional
      on the presence of children (with children: OR, 1.21 [95% CI, 0.95-1.54; p =
      .13]; without children: OR, 0.75 [95% CI, 0.56-1.02; p = .06]). CONCLUSION: Past
      focus on single mothers as a high-risk group has oversimplified the relationship
      between partner status and depression, obscuring important distinctions between
      women of different racial backgrounds.

PMID- 22964362
TI  - Review and meta-analysis of 82 studies on end-of-life management methods for
      source separated organics.
AB  - This article reports on a literature review and meta-analysis of 82 studies,
      mostly life cycle assessments (LCAs), which quantified end-of-life (EOL)
      management options for organic waste. These studies were reviewed to determine
      the environmental preferability, or lack thereof, for a number of EOL management
      methods such as aerobic composting (AC), anaerobic digestion (AD), gasification,
      combustion, incineration with energy recovery (often denoted as waste-to-energy
      incineration), mechanical biological treatment, incineration without energy
      recovery (sometimes referenced by just the word "incineration"), and landfill
      disposal with and without energy recovery from generated methane. Given the vast
      differences in boundaries as well as uncertainty and variability in results, the
      LCAs among the 82 studies provided enough data and results to make conclusions
      regarding just four EOL management methods - aerobic composting, anaerobic
      digestion, mass burn waste-to-energy (WTE), and landfill gas-to-energy (LFGTE).
      For these four, the LCAs proved sufficient to determine that aerobic composting
      and anaerobic digestion are both environmentally preferable to either WTE or
      LFGTE in terms of climate change impacts. For climate change, LCA results were
      mixed for WTE versus LFGTE. Furthermore, there is a lack of empirically reliable
      estimates of the amount of organics input to AD that is converted to energy
      output versus remaining in the digestate. This digestate can be processed through
      aerobic composting into a compost product similar to the compost output from
      aerobic composting, assuming that the same type of organic materials are managed
      under AD as are managed via AC. The magnitude of any trade-off between generation
      of energy and production of compost in an AD system appears to be critical for
      ranking AC and AD for differing types of organics diversion streams. These
      results emphasize how little we generally know, and exemplify the fact that in
      the reviewed literature no single EOL management method consistently topped all
      other management options across all environmental impacts, and that future
      studies must strive to match existing analytical boundaries and alternatives
      assessed to increase knowledge if as a community we expect to be able to make
      even more generalized conclusions.

PMID- 22964363
TI  - Development of neuropeptide Y-containing neurons in sympathetic ganglia of rats.
AB  - Expression of neuropeptide Y (NPY) in the sympathetic ganglia was investigated by
      immunohistochemistry and tract tracing. The distribution of NPY immunoreactivity
      (IR) was studied in the superior cervical ganglion (SCG), stellate ganglion (SG)
      and celiac ganglion (CG) from rats of different ages (newborn, 10-day-old, 20-day
      old, 30-day-old, 2-month-old, 6-month-old, 24-month-old). We observed that the
      percentage of NPY-IR neuronal profiles increased during early postnatal
      development. In the SCG and SG, the percentage of NPY-IR profiles enlarged in the
      first month of life from 43+/-3.6% (SCG) and 46+/-3.8% (SG) until 64+/-4.1% (SCG)
      and 58+/-3.5% (SG). The percentage of NPY-IR profiles in the CG increased during
      the period between 20days (65+/-3.8%) and 30days (82+/-5.1%) of animals' life and
      did not change in further development. In newborn and 10-day-old rats, a large
      portion of NPY-IR neurons was also calbindin D28K (CB)-IR in all sympathetic
      ganglia. The proportion of CB-IR substantially decreased during next 10days in
      the SCG, SG and CG. NPY-IR was approximately present in a half of the
      postganglionic neurons innervating muscle vessels of the neck and forearm, and
      the percentage of labeled NPY-IR profiles did not change during the development.
      Only single Ki67-IR neurons were also NPY-IR in the SCG, SG and CG in newborns
      and not in older animals. No NPY+/caspase 3+IR neurons were observed. Finally,
      the process of morphological changes in the size and percentages of NPY-IR
      profiles is complete in rats by the first month of life.

PMID- 22964364
TI  - In vitro mechanisms involved in the regulation of cell survival by lithium
      chloride and IGF-1 in human hormone-dependent breast cancer cells (MCF-7).
AB  - Lithium, the lightest of all solid elements, has been used for the treatment of
      bipolar disorder since 1970s and prescribed to millions of women worldwide.
      Lithium chloride (LiCl) has been considered to be a potent inhibitor of glycogen
      synthase kinase-3beta (GSK-3beta), a serine/threonine kinase that is involved in
      the control of cell proliferation, differentiation, and apoptosis. In addition,
      GSK-3beta has been found to be inhibited endogenously by insulin-like growth
      factor-1 (IGF-1), a potent mitogen that plays an important role in the survival,
      growth, and differentiation of normal and neoplastic cells. Although both IGF-1
      and LiCl have the ability to inhibit GSK-3beta, the specific signaling difference
      that mediates the survival of breast cancer cells was not clear. Therefore, in
      the present study, MCF-7 cells (human breast cancer cells) were treated with or
      without IGF-1 or LiCl in the presence or absence of LY294002 or PD98059
      (pharmacological inhibitors) for 24h. As the expression of signaling proteins is
      crucial in the maintenance of cell survival and apoptosis, we analyzed the cells
      using immunoblotting procedure. In summary, our results have shown that LiCl and
      IGF-1 mediates cell survival by inhibiting GSK-3beta but differ in their
      mechanisms. IGF-1 involves PI3K/Akt or MAPK pathways whereas LiCl is completely
      independent of these pathways. IGF-1 upregulates anti-apoptotic proteins whereas
      LiCl downregulates apoptotic proteins in order to maintain cell survival.

PMID- 22964365
TI  - CT imaging and histopathological features of renal epithelioid angiomyolipomas.
AB  - AIM: To describe computed tomography (CT) imaging and histopathological
      manifestations of renal epithelioid angiomyolipomas (EAMLs) for better
      understanding and cognition in the diagnosis of this new category of renal
      tumours. MATERIALS AND METHODS: Clinical data and CT images from 10 cases of EAML
      were retrospectively analysed. All patients underwent CT with and without
      contrast medium administration, with multiplanar reconstruction (MPR) when
      needed. RESULTS: Plain CT manifestations of EAMLs were a higher density of mass
      (10-25 HU) than renal parenchyma, bulging contour of the involved kidney, absence
      of fat, distinct edges without a lobulate appearance. Contrast-enhanced CT
      features were markedly heterogeneous enhancement (from rapid wash-in to slow wash
      out), large tumour size without lobular appearance, complete capsule with
      distinct margins and frequent mild necrotic areas. Histopathological features
      were epithelioid cells with eosinophilic cytoplasm, large and deeply stained
      nuclei, and dense arrangement of tumour cells with patchy necrosis; diffuse
      sheets of epithelioid cells were positive for HMB-45 (melanoma-associated
      antigen) and negative for epithelial membrane antigen (EMA) staining. CONCLUSION:
      Multiple specific CT features correlated well with the histopathology and may
      play an important role in the primary diagnosis of EAMLs.

PMID- 22964366
TI  - Does Courvoisier's sign stand the test of time?
AB  - AIM: To investigate the validity of Courvoisier's sign, in the age of cross
      sectional imaging and image analysis software by objectively measuring
      gallbladder volumes at magnetic resonance cholangiopancreatography (MRCP) in
      patients with and without biliary obstruction and to assess whether gallbladder
      volume is more significantly increased in patients with gallstone-related rather
      than non-gallstone-related biliary obstruction. MATERIALS AND METHODS: All MCRP
      investigations that were performed at a tertiary hepatobiliary centre over a 2
      year period were analysed. The information recorded included the presence or
      absence of gallbladder stones as well as the presence and type of common bile
      duct (CBD) disease. Gallbladder volume was calculated from MRCP studies using
      image analysis software. RESULTS: Three hundred and ninety-four of 645 examined
      MRCPs (61.1%) were eligible for analysis. A statistically significant difference
      in mean gallbladder volume existed between the summated obstructive and non
      obstructive groups (p < 0.001). In addition, a significant difference existed in
      mean gallbladder volume between those with CBD stones and non-gallstone CBD
      obstruction (p = 0.03). CONCLUSION: A significant difference was observed in
      gallbladder volumes in the group with biliary obstruction from
      choledocholithiasis compared with the group with biliary obstruction from other
      causes. Thus, objective measurement of gallbladder volume from modern cross
      sectional imaging studies appears to validate Courvoisier's sign as a valuable
      clinical sign, which could be applied to modern imaging studies in distinguishing
      different causes of biliary obstruction in the jaundiced patient.

PMID- 22964367
TI  - Squamous metaplasia of lactiferous ducts (SMOLD).
AB  - The aim of this review is to illustrate the mammographic and sonographic
      appearances of squamous metaplasia of the lactiferous ducts (SMOLD) and to
      discuss the disease processes of this uncommon breast disease, which shows a
      strong correlation with smoking. The most common mammographic appearance is of a
      retro-areolar asymmetrical density. Ultrasonography of the symptomatic breast
      typically shows a retro-areolar, predominately medial, ill-defined, hypoechoic
      lesion with either abscess or sinus/fistula formation. Duct dilatation and
      continuity with lactiferous ducts is commonly seen. Increased vascularity is
      occasionally seen on colour Doppler ultrasound. Pathology tissue confirmation is
      always required and this can be by histology of a core biopsy or excision
      specimen, or fine-needle aspiration (FNA) cytology. Occasionally smears of an
      associated abundant nipple or sinus discharge may be of value.

PMID- 22964368
TI  - Interventional radiology emergency service provision for a large UK urban
      population: initial 3.5 years of experience.
AB  - AIM: To review the activity and impact of an out-of-hours (OOH) interventional
      radiology service introduced in Glasgow in 2007. MATERIAL AND METHODS: A
      retrospective review of the first 42 months formal OOH activity across 11
      hospital sites covering a population of 1.2 million was undertaken. The 30 day
      mortality and cause of death was logged for each procedural subtype [nephrostomy,
      biliary and abscess drainage, enteric stenting, transjugular intrahepatic porto
      systemic shunt (TIPS), thoracic endovascular aortic aneurysm repair (TEVAR),
      endovascular, and embolization]. RESULTS: From October 2007 to March 2011, 502
      cases were identified. The mean number of procedures performed per month was 12
      (range 5-21). This represents an event rate of 12/100,000 population/year. A
      minority (11%) of cases were undertaken after midnight. The activity levels were
      stable over the 42 month study period. The most frequent procedures were
      percutaneous nephrostomy (32%) and embolization for haemorrhage (30%). Thirty-day
      mortality was 17% for the entire group but varied from 53% (biliary intervention)
      to 0% (TEVAR). There was no death following embolization for obstetric
      haemorrhage. Approximately half of the deaths were due to a failure of the
      procedure to control the underlying clinical problem. CONCLUSION: The demand for
      OOH services is important but not unduly onerous. There is no evidence of
      expansion of demand after launching such a service. Mortality rates probably
      reflect the underlying clinical status of this emergency patient group. Certain
      procedures carry a high mortality rate, raising issues of clinical judgement,
      appropriateness of intervention, and/or timing.

PMID- 22964369
TI  - Primary care in Baltic countries: a comparison of progress and present systems.
AB  - OBJECTIVES: This study aims to compare the organisation of primary care (PC)
      systems in Estonia, Latvia and Lithuania, focusing on the structure and process
      of service delivery, and to discuss the suitability of the PHAMEU instrument for
      international comparison of PC systems. METHODS: The data were collected in the
      framework of PHAMEU project during 2009-2010. The selected indicators were used
      to describe and compare the structure and process of PC in Estonia, Latvia and
      Lithuania. RESULTS: The results showed that the coordination of PC services,
      legislative framework, service delivery, quality requirements and PC financing
      principles are rather similar in all three Baltic countries. Population coverage
      for PC services, cost sharing for some services, and the employment status of
      family doctors differs by country. The PHAMEU instrument was most applicable for
      the description and comparison of the structure of PC and some aspects of the
      process. Information about patient outcome and quality of care was neither
      available nor reliable enough. CONCLUSION: The development of PC systems in
      Baltic countries has been rather similar, but some aspects also differ between
      the countries. Use of a standardized instrument allows for international
      comparison, but assumes standardised data collection procedures in comparable
      countries.

PMID- 22964370
TI  - Squamamoeba japonica n. g. n. sp. (Amoebozoa): a deep-sea amoeba from the Sea of
      Japan with a novel cell coat structure.
AB  - Squamamoeba japonica n. g. n. sp. was isolated and described from marine bottom
      sediments collected at a depth of ca. 2700 m in the Sea of Japan. Trophic amoebae
      of this species are elongated and flattened, with a wide anterior hyaloplasm
      producing numerous ventral subpseudopodia for adhesion to the substratum. The
      cell coat consists of flat oval scales tightly packed together to form a
      continuous layer separated from the plasma membrane. Amoebae can form cytoplasmic
      projections protruding through the scale layer and having tips covered only with
      the plasma membrane. Small subunit ribosomal RNA gene phylogeny shows that S.
      japonica forms a long branch in the amoebozoan tree, robustly grouping with the
      marine strain 'Pessonella' sp. PRA-29. Morphological data available for the
      latter, although scarce, give additional support for the relatedness of both
      species. The resulting clade comprising the two taxa shows no close relationships
      to other Amoebozoa and seems to be a novel lineage that developed an ability to
      temporarily liberate local areas of the plasma membrane from the cell coat
      independently from Himatismenida, Trichosida, Pellitida and Dermamoeba.

PMID- 22964372
TI  - Effects of maltreatment and early intervention on diurnal cortisol slope across
      the start of school: a pilot study.

PMID- 22964371
TI  - Disproportionate exposure to early-life adversity and sexual orientation
      disparities in psychiatric morbidity.
AB  - OBJECTIVES: Lesbian, gay, and bisexual (LGB) populations exhibit elevated rates
      of psychiatric disorders compared to heterosexuals, and these disparities emerge
      early in the life course. We examined the role of exposure to early-life
      victimization and adversity-including physical and sexual abuse, homelessness,
      and intimate partner violence-in explaining sexual orientation disparities in
      mental health among adolescents and young adults. METHODS: Data were drawn from
      the National Longitudinal Study of Adolescent Health, Wave 3 (2001-2002), a
      nationally representative survey of adolescents. Participants included
      gay/lesbian (n=227), bisexual (n=245), and heterosexual (n=13,490) youths, ages
      18-27. We examined differences in the prevalence of exposure to child physical or
      sexual abuse, homelessness or expulsion from one's home by caregivers, and
      physical and sexual intimate partner violence according to sexual orientation.
      Next we examined the associations of these exposures with symptoms of
      psychopathology including suicidal ideation and attempts, depression, binge
      drinking, illicit drug use, tobacco use, alcohol abuse, and drug abuse. Finally,
      we determined whether exposure to victimization and adversity explained the
      association between sexual orientation and psychopathology. RESULTS: Gay/lesbian
      and bisexual respondents had higher levels of psychopathology than heterosexuals
      across all outcomes. Gay/lesbian respondents had higher odds of exposure to child
      abuse and housing adversity, and bisexual respondents had higher odds of exposure
      to child abuse, housing adversity, and intimate partner violence, than
      heterosexuals. Greater exposure to these adversities explained between 10 and 20%
      of the relative excess of suicidality, depression, tobacco use, and symptoms of
      alcohol and drug abuse among LGB youths compared to heterosexuals. Exposure to
      victimization and adversity experiences in childhood and adolescence
      significantly mediated the association of both gay/lesbian and bisexual
      orientation with suicidality, depressive symptoms, tobacco use, and alcohol
      abuse. CONCLUSIONS: Exposure to victimization in early-life family and romantic
      relationships explains, in part, sexual orientation disparities in a wide range
      of mental health and substance use outcomes, highlighting novel targets for
      preventive interventions aimed at reducing these disparities.

PMID- 22964373
TI  - Quantitative CT analysis of small pulmonary vessels in lymphangioleiomyomatosis.
AB  - BACKGROUNDS: Lymphangioleiomyomatosis (LAM) is a destructive lung disease that
      share clinical, physiologic, and radiologic features with chronic obstructive
      pulmonary disease (COPD). This study aims to identify those features that are
      unique to LAM by using quantitative CT analysis. METHODS: We measured total cross
      sectional areas of small pulmonary vessels (CSA) less than 5mm(2) and 5-10mm(2)
      and calculated percentages of those lung areas (%CSA), respectively, in 50 LAM
      and 42 COPD patients. The extent of cystic destruction (LAA%) and mean
      parenchymal CT value were also calculated and correlated with pulmonary function.
      RESULTS: The diffusing capacity for carbon monoxide/alveolar volume (DL(CO)/VA
      %predicted) was similar for both groups (LAM, 44.4 +/- 19.8% vs. COPD, 45.7 +/-
      16.0%, p=0.763), but less tissue damage occurred in LAM than COPD (LAA% 21.7 +/-
      16.3% vs. 29.3 +/- 17.0; p<0.05). Pulmonary function correlated negatively with
      LAA% (p<0.001) in both groups, yet the correlation with %CSA was significant only
      in COPD (p<0.001). When the same analysis was conducted in two groups with equal
      levels of LAA% and DL(CO)/VA %predicted, %CSA and mean parenchymal CT value were
      still greater for LAM than COPD (p<0.05). CONCLUSIONS: Quantitative CT analysis
      revealing a correlation between cystic destruction and CSA in COPD but not LAM
      indicates that this approach successfully reflects different mechanisms governing
      the two pathologic courses. Such determinations of small pulmonary vessel density
      may serve to differentiate LAM from COPD even in patients with severe lung
      destruction.

PMID- 22964374
TI  - Comparison of thiol subproteome of the vent mussel Bathymodiolus azoricus from
      different Mid-Atlantic Ridge vent sites.
AB  - Deep-sea hydrothermal mussels Bathymodiolus azoricus live in the mixing zone
      where hydrothermal fluid mixes with bottom seawater, creating large gradients in
      the environmental conditions and are one of the most studied hydrothermal species
      as a model of adaptation to extreme conditions. Thiol proteins, i.e. proteins
      containing a thiol or sulfhydryl group (SH) play major roles in intracellular
      stress defense against reactive oxygen species (ROS) and are especially
      susceptible to oxidation. However, they are not particularly abundant,
      representing a small percentage of proteins in the total proteome and therefore
      are difficult to study by proteomic approaches. Activated thiol sepharose (ATS)
      was used for the rapid and quantitative selection of proteins comprising thiol-
      or disulfide-containing subproteomes. This study aims to isolate thiol-containing
      proteins from the gills of B. azoricus collected in distinct hydrothermal vents
      and to study the thiol-containing subproteome as a function of site-specific
      susceptibility to ROS. Results show that ATS is a powerful tool to isolate the
      thiol-containing sub-proteome and differently-expressed protein spots showed
      significant differences among the three vent sites, supporting previous findings
      that specific environmental conditions are crucial for ROS formation and that B.
      azoricus have different susceptibilities to oxidative stress depending on the
      vent site they inhabit.

PMID- 22964375
TI  - Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads
      to decreased adhesion and paclitaxel-induced chemoresistance.
AB  - OBJECTIVE: Chemoresistance is a critical feature of advanced ovarian cancer with
      only 30% of patients surviving longer than 5 years. We have previously shown that
      four kallikrein-related (KLK) peptidases, KLK4, KLK5, KLK6 and KLK7 (KLK4-7), are
      implicated in peritoneal invasion and tumour growth, but underlying mechanisms
      were not identified. We also reported that KLK7 overexpression confers
      chemoresistance to paclitaxel, and cell survival via integrins. In this study, we
      further explored the functional consequenses of overexpression of all four KLKs
      (KLK4-7) simultaneously in the ovarian cancer cell line, OV-MZ-6, and its impact
      on integrin expression and signalling, cell adhesion and survival as contributors
      to chemoresistance and metastatic progression. METHODS: Quantitative gene and
      protein expression analyses, confocal microscopy, cell adhesion and
      chemosensitivity assays were performed. RESULTS: Expression of
      alpha5beta1/alphavbeta3 integrins was downregulated upon combined stable KLK4-7
      overexpression in OV-MZ-6 cells. Accordingly, the adhesion of these cells to
      vitronectin and fibronectin, the extracellular matrix binding proteins of
      alpha5beta1/alphavbeta3 integrins and two predominant proteins of the peritoneal
      matrix, was decreased. KLK4-7-transfected cells were more resistant to paclitaxel
      (10-100 nmol/L: 38-54%), but not to carboplatin, which was associated with
      decreased apoptotic stimuli. However, the KLK4-7-induced paclitaxel resistance
      was not blocked by the MEK1/2 inhibitor, U0126. CONCLUSIONS: This study
      demonstrates that combined KLK4-7 expression by ovarian cancer cells promotes
      reduced integrin expression with consequently less cell-matrix attachment, and
      insensitivity to paclitaxel mediated by complex integrin and MAPK independent
      interactions, indicative of a malignant phenotype and disease progression
      suggesting a role for these KLKs in this process.

PMID- 22964376
TI  - The relationship between sleep quality and daytime sleepiness and various
      anthropometric parameters in stable patients undergoing hemodialysis.
AB  - OBJECTIVE: This study evaluates the relationship between sleep quality and
      daytime sleepiness and body mass index (BMI), waist circumference (WC), waist to
      hip ratio (WHR), and conicity index in stable patients undergoing hemodialysis
      (HD). DESIGN AND METHODS: This was a cross-sectional study. Patients regularly
      received dialysis treatment in a state hospital. Study participants had a medical
      history taken and underwent physical examination, measurement of anthropometric
      factors, and calculations (including BMI, WC, WHR, and confidence interval [CI])
      and biochemical analysis. We evaluated quality of life with the 36-item short
      form survey (SF-36) and depressive symptoms with the Beck Depression Inventory
      (BDI). Self-reported sleep quality (using the Pittsburgh Sleep Quality Index
      [PSQI]) and daytime sleepiness (using the Epworth Sleepiness Scale (ESS) was
      recorded for all patients. RESULTS: In total, 101 patients undergoing HD were
      enrolled. Stepwise linear regression analysis of factors revealed that BMI (b
      [partial regression coefficient], 0.405; CI, 0.177-0.632; P, .001), WC (b, 0.082;
      CI, 0.008-0.157; P, .031), BDI score (b, 0.091; CI, 0.032-0.149; P, .003),
      presence of diabetes (b, 1.621; CI, 0.175-3.068; P, .028), and presence of
      cerebrovascular disease (b, 1.944; CI, 0.103-3.785; P,.039) were related to PSQI
      score (as a dependent variable). Using the same independent parameters, only the
      physical component summary score of the SF-36 was independently related to the
      ESS score (b, -0.120; CI, -0.190 to -0.049; P, .001). None of the anthropometric
      parameters was related to ESS. CONCLUSIONS: BMI and WC were the only parameters
      found to be related to sleep disturbance. None of the anthropometric parameters
      was related to daytime sleepiness.

PMID- 22964377
TI  - Insulin sensitivity, but not hyperglycemia, may be superior as a prognostic
      marker and therapeutic target for diabetes in heart failure.

PMID- 22964379
TI  - Atrial fibrillation in obstructive sleep apnea: atrial arrhythmogenic substrate
      of a different sort.

PMID- 22964380
TI  - A switch based on self-assembled thymine.
AB  - The DNA base thymine is deposited at 100 K on Cu(111) and investigated and
      manipulated by low-temperature scanning tunneling microscopy at 5 K. At
      submonolayer coverage paired rows are observed. At monolayer coverage a hexagonal
      commensurate self-assembled layer with the methyl group pointing away from the
      surface forms. A reversible local manipulation of molecules within the self
      assembled layer is demonstrated. This manipulation is interpreted as an out-of
      plane relaxation of molecules within the layer induced by the change of the
      adsorption geometry of individual molecules between two meta-stable orientations.
      A positive field of 2-4 V leads to this local change in the molecular
      arrangement, while a field larger than 4 V restores the original geometry.

PMID- 22964381
TI  - Tubular waveguide evanescent field absorption biosensor based on particle plasmon
      resonance for multiplex label-free detection.
AB  - A novel tubular waveguide particle plasmon resonance (TW-PPR) sensor is
      demonstrated for label-free biochemical detection. The sensor itself is a
      microchamber of a defined sample volume, a mechanical support for sensor coating,
      a waveguide to provide evanescent wave interrogation, and it can be easily
      extended to a multi-channel format. The sensor resolution is estimated to be
      2.6*10(-6) RIU in measuring solutions of various refractive indices. The sensing
      system can perform multiple measurements simultaneously and its limit of
      detection for anti-DNP antibody and streptavidin is 1.2*10(-10) g/ml (0.55 pM)
      and 2.3*10(-10) g/ml (3.5 pM), respectively. Accurate determination of these
      analytes with known concentration spiked in artificial urine were examined and
      the bias is less than +/-7%, supporting the utility of the device for analyte
      screening in more complex media. The TW-PPR sensor can be inexpensively
      fabricated and has a special niche for monitoring biomolecular interactions in
      real-time, hence it is ideally suitable for disposable uses, especially promising
      for convenient high-throughput biochemical sensing applications.

PMID- 22964382
TI  - Direct electrochemistry of glucose oxidase at electrochemically reduced graphene
      oxide-multiwalled carbon nanotubes hybrid material modified electrode for glucose
      biosensor.
AB  - Direct electrochemistry of glucose oxidase (GOx) at an electrochemically reduced
      graphene oxide-multiwalled carbon nanotubes hybrid (ERGO-MWCNT) modified glassy
      carbon electrode (GCE) has been reported. The pi-pi stacking interaction
      operating between the MWCNT and graphene oxide (GO) has been revealed by UV-Vis
      absorption spectroscopy. GOx was well immobilized onto the ERGO-MWCNT hybrid
      film, as a result direct electrochemistry of GOx has been achieved. Compared with
      pristine MWCNT, 2.1 fold higher peak current and very low peak to peak separation
      (DeltaE(p)) of 26 mV were observed at the hybrid film, demonstrating faster
      electron transfer between GOx and the modified electrode surface. Moreover, the
      modified film exhibited high electrocatalytic activity towards glucose via
      reductive detection of oxygen consumption and in the presence of mediator. The
      proposed biosensor exhibits low detection limit of 4.7 MUM with wide linear range
      of 0.01-6.5mM and acquires excellent storage and operational stabilities. The
      accurate glucose determination in human blood serum and good recoveries achieved
      in spiked urine samples revealed their great potential in the practical
      applications.

PMID- 22964383
TI  - High sensitive trypsin activity evaluation applying a nanostructured QCM-sensor.
AB  - The medical diagnostic, the industry, and the biotechnology require rapid,
      sensitive, and easy to use methods for trypsin activity determination. A simple
      approach, which meets all these requirements, based on Quartz Crystal
      Microbalance (QCM) was developed, analytically characterized and described in the
      present work. QCM application allows rapid trypsin activity evaluation by real
      time monitoring of the enzymatic degradation of the substrate. The new approach
      suggested in this work takes advantage of nanoparticles loaded gelatin employment
      as a trypsin substrate, deposited on the QCM crystal. The heavy nanoparticles
      leave the substrate layer together with the products of its enzymatic degradation
      provoking thus a greater decrease of the total QCM crystal mass compared with the
      non charged substrate. As a result, a higher sensor frequency response occurs. A
      10 fold improvement of the LOD was achieved for trypsin activity evaluation
      applying the proposed method with Ag nanoparticles loaded gelatin (7.5*10(-4) U
      mL(-1) vs. 7.5*10(-3) U mL(-1) obtained by the "classic" QCM method). The
      approach subject of this work can be applied with any substrate degrading enzyme.

PMID- 22964384
TI  - Immunodetection of 17beta-estradiol in serum at ppt level by microcantilever
      resonators.
AB  - To date control strategies in detecting anabolic agents for promoting growth of
      food producing animals are mainly related to screening techniques based on
      immunochemical and physiochemical methods, whose major limit is represented by
      relative low analytical sensitivity. As a consequence, consumers are currently
      exposed to molecules with potential carcinogenic effects such as 17beta
      estradiol, the most powerful substance with estrogenic effect. Therefore, high
      analytical sensitivity screening and confirmatory methods are required, coupling
      easiness of use and efficiency. We here report on the immunodetection of 17beta
      estradiol in serum by antibody-immobilized microcantilever resonators, an
      innovative biosensing platform able to quantify an adsorbed target mass (such as
      cells, nucleic acids, biomolecules, etc.) thanks to a shift in resonance
      frequency. Our tool based on microcantilever resonator arrays has shown to be
      capable of discriminating treated and untreated animals, showing the ability of
      detecting traces of 17beta-estradiol in serum at concentrations lower than the
      present accepted physiological serum concentration threshold value (40 ppt) and
      commercial ELISA tests (25 ppt). The method exhibits a limit of detection of 20
      ppt and a limited cross-reactivity with high concentrations (10 ppb) of similar
      molecules (testosterone).

PMID- 22964385
TI  - Development of a novel cyano group containing electrochemically deposited polymer
      film for ultrasensitive simultaneous detection of trace level cadmium and lead.
AB  - Poly(diphenylamine-co-2-aminobenzonitrile) (P(DPA-co-2ABN)), a cyano group
      containing conducting polyaniline derivative, has been electrodeposited developed
      as the new material and utilized for the simultaneous electrochemical
      determination of trace levels of cadmium (Cd(2+)) and lead (Pb(2+)). P(DPA-co
      2ABN) film preconcentrates effectively through cyano chelation and
      electrochemically strips the heavy metal ions with well separated potentials,
      which are beneficially utilized for ppb level simultaneous detection of Cd(2+)
      and Pb(2+). Differential pulse voltammetry studies revealed that Cd(2+) and
      Pb(2+) ions were simultaneously stripped with well-defined, separated and sharp
      peaks for Cd(2+) and Pb(2+). The influence of various operational parameters such
      as pulse amplitude, pulse time, scan rate, initial potential, end potential,
      accumulation potential and accumulation time on the electrochemical stripping of
      heavy metals were investigated in details. Under the optimal conditions, good
      linear correlations were obtained from 1.26 to 907.8 ppm for Cd(2+) and 0.26 to
      58.73 ppm for Pb(2+), respectively. Low detection limits for Cd(2+) and Pb(2+),
      0.255 ppm and 0.165 ppm, respectively, were observed. The practical utility of
      the new procedure was demonstrated in real samples.

PMID- 22964386
TI  - Enantioselective behavior of malathion enantiomers in toxicity to beneficial
      organisms and their dissipation in vegetables and crops.
AB  - The dissipation behavior of the two enantiomers of malathion was elucidated in
      five plant species using enantioselective high performance liquid chromatography
      (HPLC), and the acute toxicity of the individual enantiomers toward earthworms
      and honeybees was studied. The calculated LC(50) values of the R-, S- and rac
      malathion to earthworms were 0.3869, 25.17, and 19.19 MUg/cm(2), respectively,
      while the calculated LC(50) values of R-, S- and rac-malathion to bees were 2.15,
      36.67, and 7.11 MUg/mL, respectively. This indicated that the R-enantiomer was
      more toxic than S-enantiomer. The results of the degradation of racemate in
      Chinese cabbage and rape showed that the inactive S-(-)-enantiomer degraded
      faster than the active R-(+)-enantiomer. Inversely, we found a preferential
      degradation of the R-(+)-enantiomer in sugar beet. However, the degradation of
      malathion in paddy rice and wheat were nonenantioselectivity. In all plants,
      malathion was degraded to levels <10% after 5 days, and the calculated t(1/2)
      values of the enantiomers ranged from 0.83 to 1.43 days in these five plants. In
      conclusion, our findings of enantioselectivity in the environmental fate and
      acute toxicity of the malathion enantiomers may have implications for better
      environmental and ecological risk assessment for chiral pesticides in general.

PMID- 22964387
TI  - Influence of the pore structure and surface chemistry on adsorption of
      ethylbenzene and xylene isomers by KOH-activated multi-walled carbon nanotubes.
AB  - To investigate the effect of pore structure and surface chemistry on adsorption
      of monoaromatics, multi-walled carbon nanotubes (MWCNTs) with different specific
      surface area (SSA) and surface oxygen content by KOH activation treatment have
      been prepared. The results indicate that adsorption of four test chemicals is
      enhanced by 2-3, 7-9 and 10-13 times for CNTs-K1 (MWCNTs:KOH=1:1), CNTs-K4
      (MWCNTs:KOH=1:4) and CNTs-K6 (MWCNTs:KOH=1:6) as justified by the ratios of
      adsorption coefficient. Adsorption properties of ethylbenzene and xylene isomers
      (EX) by activated-MWCNTs depend significantly on mesopore volumes and hydroxyl
      groups. There are strong positive correlations between the adsorption capacity
      (or adsorption affinity) and mesopore volumes or hydroxyl groups. Mesopore
      filling could be a predominant mechanism governing monoarmatics adsorption onto
      activated-MWCNTs, contributing more than simply increasing SSA. The hydroxyl
      groups at low concentration can improve diffusion of MWCNTs in water, which could
      be favorable for aqueous phase adsorption. However, it is not large enough to
      form a lot of water clusters to hinder EX adsorption. This is the first
      systematic study of the influence of physicochemical properties on adsorption of
      monoaromatics onto activated-MWCNTs by qualitative and quantitative analysis, and
      results highlight the synergetic effects of porosity and surface chemistry in
      controlling adsorption of monoaromatics onto MWCNTs in wastewater treatment.

PMID- 22964388
TI  - Treatment of azo dye-containing wastewater by a Fenton-like process in a
      continuous packed-bed reactor filled with activated carbon.
AB  - In this work, oxidation with a Fenton-like process of a dye solution was carried
      out in a packed-bed reactor. Activated carbon Norit RX 3 Extra was impregnated
      with ferrous sulfate and used as catalyst (7 wt.% of iron). The effect of the
      main operating conditions in the Chicago Sky Blue (CSB) degradation was analyzed.
      It was found that the increase in temperature leads to a higher removal of the
      dye and an increased mineralization. However, it also increases the iron
      leaching, but the values observed were below 0.4 ppm (thus, far below European
      Union limits). It was possible to reach, at steady-state, a dye conversion of
      88%, with a total organic carbon (TOC) removal of ca. 47%, being the reactor
      operated at 50 degrees C, pH 3, W(cat)/Q=4.1 g min mL(-1) (W(cat) is the mass of
      catalyst and Q the total feed flow rate) and a H(2)O(2) feed concentration of
      2.25 mM (for a CSB feed concentration of 0.012 mM). The same performance was
      reached in three consecutive cycles.

PMID- 22964389
TI  - Magnetic nanoparticles and quantum dots co-loaded imprinted matrix for
      pentachlorophenol.
AB  - In this study, an imprinted silica matrix of pentachlorophenol (PCP) co-loaded
      with Fe(3)O(4) nanoparticles and ZnS:Mn(2+) quantum dots (QDs) was fabricated.
      The introduction of Fe(3)O(4) nanoparticles to the imprinted matrix provided an
      easy way to separate PCP under an external magnetic field. ZnS:Mn(2+) QDs offered
      a readout signal to monitor the amount of PCP bound to the imprinted matrix and
      evaluate the efficiency of imprinting. X-ray diffraction, transmission electron
      microscopy, Fourier transform infrared spectroscopy were used to characterize the
      imprinted matrix. The low angle X-ray diffraction and N(2) adsorption-desorption
      analysis indicated a periodic mesoporous structure. The as-synthesized imprinted
      matrix preferred to adsorb PCP rather than the other aromatic compounds like 2,4
      dichlorophenoxy acetic acid, 2,4-dichlorophenol and phenol. The recoveries of
      spiked PCP in spring water and tap water with Fe(3)O(4)-ZnS:Mn(2+) co-loaded MIPs
      are 101% and 97%, respectively.

PMID- 22964390
TI  - Characterisation of organic matter associated with groundwater arsenic in
      reducing aquifers of southwestern Taiwan.
AB  - Arsenic (As) in groundwaters extensively used by people across the world
      constitutes a serious public health threat. The importance of organic matter (OM)
      as an electron donor in microbially-mediated reduction of As(V) or Fe(III)
      bearing As-host minerals leading to mobilisation of solid-phase arsenic is widely
      recognised. Notwithstanding this, there are few studies characterising OM in such
      aquifers and, in particular, there is a dearth of data from the classic arsenic
      bearing aquifers in southwestern Taiwan. Organic geochemical analyses of
      sediments from a known groundwater arsenic hot-spot in southwestern Taiwan
      revealed contributions of thermally mature and plant derived origin, consistent
      with OM sources in all other Asian groundwater aquifer sediments analysed to
      date, indicating comparable sources and routes of OM transfer. The combined
      results of amended As(V) reduction assays with the organic geochemical analysis
      revealed that the microbiological process of dissimilatory As(V) reduction is
      active in this aquifer, but it is not controlled by a specific source of analysed
      OM. These indicate that (i) part of the OM that was considered to be less bio
      available could still be used as an electron donor or (ii) other electron donors,
      not analysed in present study, could be controlling the rate of As release. 

PMID- 22964391
TI  - Mechanistic studies on the release of lysozyme from twin-screw extruded lipid
      implants.
AB  - The influence of lipid melting on the in-vitro release of lysozyme from twin
      screw extruded lipid implants was investigated. Triglyceride based implants were
      prepared by admixing of glycerol tristearin and various low melting lipids and
      subsequent twin-screw extrusion (tsc-extrusion) of these mixtures at moderate
      temperatures. Lysozyme was embedded as model protein and PEG 4000 or PEG 6000 was
      used as pore-forming excipient. By decreasing the amount of pore-forming agent
      from 40% to 0% lysozyme release became more sustained and the release kinetics
      changed from a matrix-type release profile to a linear release profile.
      Differential scanning calorimetry, X-ray diffraction and scanning electron
      microscopy measurements showed a change in implant structure upon long-term
      release (240 days) at 37  degrees C which was explained by partial matrix
      melting. In addition, partial melting of the implants was found to facilitate
      complete drug release at 37  degrees C whereas at 20  degrees C without partial
      melting 20% to 90% of the incorporated protein remained trapped in the implant
      matrix. In conclusion, partial melting of the implants during in-vitro release
      was found to be a major factor for the control of protein release from extruded
      implants and can be useful to trigger release, achieve in-vivo biodegradability
      and complete long-term protein release.

PMID- 22964393
TI  - In-vivo biodegradation of extruded lipid implants in rabbits.
AB  - In-vitro studies with twin-screw extruded triglyceride based implants showed
      promising erosion behavior. However, little is known about the behavior of such
      systems in-vivo and therefore a degradability study was performed in a rabbit
      model. Four formulations were used to prepare tsc-extrudates and implanted in
      rabbits and mass loss of the implants was measured after one, three and six
      months. Samples were additionally assessed by differential scanning calorimetry
      (DSC) and scanning electron microscopy (SEM). A time dependent in-vivo erosion of
      the triglyceride matrices was detected and only 24% (+/- 17%) of the matrix
      material was recovered after 6 months of incubation (n=9). The application of a
      pore forming agent resulted in higher mass loss and an accelerated degradation
      rate. Exchange of the type of low melting triglyceride during preparation
      resulted in a better preservation of the porous implant structure, explained by a
      higher melting point of the alternate low-melting lipid. The good in-vivo
      degradability of tsc-extrudates was explained by the composition of the implants
      and the application of a low melting lipid which allowed partial melting of the
      implant at body temperature and rendered the implants more susceptible to
      degradation processes (e.g. lipolyses).

PMID- 22964392
TI  - Subcellular trafficking and transfection efficacy of polyethylenimine
      polyethylene glycol polyplex nanoparticles with a ligand to melanocortin receptor
      1.
AB  - We have synthesized and investigated properties of new PEI-PEG-based polyplexes
      containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (targeted
      polyplexes), and control polyplexes without this ligand peptide (non-targeted
      polyplexes). The targeted polyplexes demonstrated receptor-mediated transfection
      of Cloudman S91 (clone M-3) murine melanoma cells that was more efficient than
      with the non-targeted ones. Transfection with the targeted polyplexes was
      inhibited by chlorpromazine, an inhibitor of the clathrin-mediated endocytosis
      pathway, and, to a lesser extent, by filipin III or nystatin, inhibitors of the
      lipid-raft endocytosis pathway, whereas transfection with the non-targeted
      polyplexes was inhibited mainly by nystatin or filipin III. The targeted
      polyplexes caused significantly higher in vivo transfection of melanoma tumor
      cells after intratumoral administration compared to the non-targeted control. The
      targeted polyplexes carrying the HSVtk gene, after ganciclovir administration,
      more efficiently inhibited melanoma tumor growth and prolonged the lifespan of
      DBA/2 tumor-bearing mice compared to the non-targeted ones. Packed targeted
      polyplexes appeared and accumulated in the melanoma cells 6h earlier than the non
      targeted ones. The targeted polyplexes enter into the nuclei of the melanoma
      cells more rapidly than the non-targeted control, and this difference may also be
      attributed to processes of receptor-mediated endocytosis. We believe that these
      data may be useful for the optimization of polyplex systems.

PMID- 22964395
TI  - Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted
      cancer imaging.
AB  - Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated
      blood vessels and extracellular matrix, and thus is a promising cancer biomarker.
      Very recently, we developed a novel class of high-affinity (<100nM) peptides,
      termed 'aptides', that specifically bind a variety of protein targets. Here, we
      describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB
      specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer.
      An anti-EDB aptide (APT(EDB)) containing an additional cysteine residue reacted
      with maleimide-terminated, PEGylated phospholipid (Mal-PEG(2000)-DSPE) to give an
      aptide-conjugated PEGylated phospholipid (APT(EDB)-PEG(2000)-DSPE). A
      nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with
      amphiphilic phospholipids, including APT(EDB)-PEG(2000)-DSPE, methoxy-PEG(2000)
      DSPE, and rhodamine-DMPE. The resulting nanoparticles (APT(EDB)-SPIONs) had a
      hydrodynamic size of less than 50 nm and remained stable in an aqueous solution
      for at least 1week. In in vitro studies, APT(EDB)-SPIONs showed specific uptake
      by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that
      expresses a high level of the target EDB protein, MRI clearly revealed that
      APT(EDB)-SPIONs injected via the tail vein specifically accumulated at the tumor
      site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake
      in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed
      that the distribution of nanoparticles within the tumor tissue was well
      correlated with the areas where EDB was expressed. Our APT(EDB)-SPIONs hold high
      potential as a specific imaging modality for the detection of EDB-overexpressing
      tumors.

PMID- 22964394
TI  - Reversal of experimental Laron Syndrome by xenotransplantation of
      microencapsulated porcine Sertoli cells.
AB  - Recombinant human IGF-1 currently represents the only available treatment option
      for the Laron Syndrome, a rare human disorder caused by defects in the gene
      encoding growth hormone receptor, resulting in irreversibly retarded growth.
      Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in
      females and 19% in males), while burdening the patients with severe side effects,
      including hypoglycemia, in association with the unfair chore of taking multiple
      daily injections that cause local intense pain. In this study, we have
      demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli
      cells, producing pig insulin-like growth factor-1, successfully promoted
      significant proportional growth in the Laron mouse, a unique animal model of the
      human Laron Syndrome. These findings indicate a novel, simply, safe and
      successful method for the cell therapy-based cure of the Laron Syndrome,
      potentially applicable to humans.

PMID- 22964396
TI  - Evaluation of the relevance of the glassy state as stability criterion for freeze
      dried bacteria by application of the Arrhenius and WLF model.
AB  - The aim of this work was to describe the temperature dependence of microbial
      inactivation for several storage conditions and protective systems (lactose,
      trehalose and dextran) in relation to the physical state of the sample, i.e. the
      glassy or non-glassy state. The resulting inactivation rates k were described by
      applying two models, Arrhenius and Williams-Landel-Ferry (WLF), in order to
      evaluate the relevance of diffusional limitation as a protective mechanism. The
      application of the Arrhenius model revealed a significant decrease in activation
      energy E(a) for storage conditions close to T(g). This finding is an indication
      that the protective effect of a surrounding glassy matrix can, at least, partly
      be ascribed to its inherent restricted diffusion and mobility. The application of
      the WLF model revealed that the temperature dependence of microbial inactivation
      above T(g) is significantly weaker than predicted by the universal coefficients.
      Thus, it can be concluded that microbial inactivation is not directly linked with
      the mechanical relaxation behavior of the surrounding matrix as it was reported
      for viscosity and crystallization phenomena in case of disaccharide systems.

PMID- 22964397
TI  - HeMoLab--Hemodynamics Modelling Laboratory: an application for modelling the
      human cardiovascular system.
AB  - In this work we present HeMoLab (Hemodynamics Modeling Laboratory), a
      computational environment for modeling the Human Cardiovascular System. Its
      integrates novel computational tools, running from medical image processing to
      numerical simulation and visualization. As a simulation tool, it allows to
      accommodate complex physiological and/or pathophysiological (virtual) scenarios
      aimed to retrieve detailed information from the numerical computations. Such
      application makes possible to speed up research in the study and analysis of the
      cardiovascular system and, to provide a virtual laboratory for medical training
      and education, and specialized Human Resources development. In order to
      demonstrate the modeling and simulation capabilities of HeMoLab some cases of use
      are presented.

PMID- 22964398
TI  - Predicting biological activity: computational approach using novel distance based
      molecular descriptors.
AB  - Four novel distance based molecular descriptors termed as superpendentic
      eccentric distance sum indices 1-4 (denoted by:?P-1EDS, ?P-2EDS, ?P-3EDS and ?P
      4EDS) as well as their topochemical counterparts (denoted by:?cP-1EDS, ?cP-2EDS,
      ?cP-3EDS and ?cP-4EDS) have been conceptualized and developed in the present
      study. The sensitivity towards branching, discriminating power, and degeneracy of
      the proposed novel descriptors were investigated. Utility of these indices was
      investigated for development of models through decision tree and moving average
      analysis for the prediction of human corticotropin releasing factor-1 receptor
      binding affinity of substituted pyrazines. A wide variety of 46 2D and 3D
      molecular descriptors including proposed indices was employed for development of
      models through decision tree and moving average analysis. The calculation of most
      of these descriptors for each compound of the dataset was performed using online
      E-Dragon software (version 1.0). An in-house computer programme was also employed
      to calculate additional topological descriptors which did not figure in E-Dragon
      software. The decision tree classified and correctly predicted the input data
      with an impressive accuracy of 92% in the training set and 71% during cross
      validation. A total of three descriptors, identified by decision tree, were
      subsequently utilized for development of suitable models using moving average
      analysis. These models predicted human corticotropin releasing factor-1 receptor
      binding affinity with an accuracy of >=85%. The statistical significance of
      models was assessed through sensitivity, specificity and Matthew's correlation
      coefficient. High discriminating power, high sensitivity towards branching
      amalgamated with negligible degeneracy offer proposed descriptors a vast
      potential for use in the quantitative structure-activity/property/toxicity
      relationships so as to facilitate drug design.

PMID- 22964399
TI  - Polymer coating of carrier excipients modify aerosol performance of adhered drugs
      used in dry powder inhalation therapy.
AB  - The potential of excipient coating to enhance aerosol performance of micronized
      drugs in carrier excipient-drug blends, used in dry powder inhalers, was
      investigated. Both EC (ethyl cellulose) and PVP (polyvinylpyrrolidone) were used
      as coating agents. Carriers were prepared via sieve fractioning followed by spray
      drying, with and without polymer additive. Each uncoated and coated carrier
      salbutamol sulphate (SS) blended systems were evaluated for particle size,
      morphology, drug carrier adhesion and aerosolisation performance, after blending
      and storage for 24h. All carrier-based systems prepared had similar particle
      sizes and morphologies. The surface chemistries of the carriers were
      significantly different, as was drug-carrier adhesion and aerosolisation
      performance. Particle adhesion between SS and aerosol performance (fine particle
      fraction; FPF) followed the rank: PVP coated>un-coated>EC coated lactose. This
      rank order could be attributed to the surface energy measured by contact
      goniometry and related to the chemistry of lactose and each polymer. Storage did
      not significantly affect aerosol performance, however a rank increase in mean FPF
      value was observed for uncoated and EC coated lactose. Finally, the net
      electrostatic charge across the aerosol cloud indicated that the EC coated
      lactose transferred less charge to SS particles. The performance of each carrier
      system could be attributed to the carrier surface chemistry and, in general, by
      careful selection of the coating polymer, drug-carrier adhesion, electrostatic
      charge and aerosol performance could be controlled.

PMID- 22964400
TI  - Major perfluoroalkyl acid (PFAA) concentrations and influence of food consumption
      among the general population of Daegu, Korea.
AB  - Perfluoroalkyl acids (PFAAs) have been used in various industrial and consumer
      products for decades, and have consequently been detected in human blood
      worldwide. In the present study, general adult population in Daegu, Korea (n=140,
      >20 years of old) was recruited, collected for serum, and analyzed for 13 major
      PFAAs. The influence of dietary and water consumption on serum PFAA levels was
      also evaluated. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid
      (PFOA), and perfluorohexane sulfonic acid (PFHxS) were frequently detected with
      relatively higher concentrations in blood serum. Most PFAA concentrations except
      for PFOA were detected in higher concentrations among males, and were positively
      correlated with age and body mass index (BMI). PFOA concentrations were
      relatively higher among the female of childbearing age, e.g., 20-49years old,
      raising concerns on potential impacts on fetus through transplacental transfer or
      lactation. In addition, the concentrations of PFOA in Daegu population were
      higher than other areas of Korea, suggesting a presence of distinctive sources in
      the area. Among food items, potato consumption was identified to be significant
      contributor to serum PFOA. For PFUnDA and PFTrDA levels, intake of fish/shellfish
      was positively associated. The results of this study will be useful in developing
      public health management options for PFAAs.

PMID- 22964401
TI  - Assessment of the effects of the Japanese shift to lead-free solders and its
      impact on material substitution and environmental emissions by a dynamic material
      flow analysis.
AB  - Lead-free electronics has been extensively studied, whereas their adoption by
      society and their impact on material substitution and environmental emissions are
      not well understood. Through a material flow analysis (MFA), this paper explores
      the life cycle flows for solder-containing metals in Japan, which leads the world
      in the shift to lead-free solders in electronics. The results indicate that the
      shift has been progressing rapidly for a decade, and that substitutes for lead in
      solders, which include silver and copper, are still in the early life cycle
      stages. The results also show, however, that such substitution slows down during
      the late life cycle stages owing to long electronic product lifespans. This
      deceleration of material substitution in the solder life cycle may not only
      preclude a reduction in lead emissions to air but also accelerate an increase in
      silver emissions to air and water. As an effective measure against ongoing lead
      emissions, our scenario analysis suggests an aggressive recycling program for
      printed circuit boards that utilizes an existing recycling scheme.

PMID- 22964402
TI  - Multi-criteria analysis towards the new end use of recycled water for household
      laundry: a case study in Sydney.
AB  - This paper aims to put forward several management alternatives regarding the
      application of recycled water for household laundry in Sydney. Based on different
      recycled water treatment techniques such as microfiltration (MF), granular
      activated carbon (GAC) or reverse osmosis (RO), and types of washing machines
      (WMs), five alternatives were proposed as follows: (1) do nothing scenario; (2)
      MF+existing WMs; (3) MF+new WMs; (4) MF-GAC+existing WMs; and (5) MF-RO+existing
      WMs. Accordingly, a comprehensive quantitative assessment on the trade-off among
      a variety of issues (e.g., engineering feasibility, initial cost, energy
      consumption, supply flexibility and water savings) was performed over the
      alternatives. This was achieved by a computer-based multi-criteria analysis (MCA)
      using the rank order weight generation together with preference ranking
      organization method for enrichment evaluation (PROMETHEE) outranking techniques.
      Particularly, the generated 10,000 combinations of weights via Monte Carlo
      simulation were able to significantly reduce the man-made errors of single fixed
      set of weights because of its objectivity and high efficiency. To illustrate the
      methodology, a case study on Rouse Hill Development Area (RHDA), Sydney,
      Australia was carried out afterwards. The study was concluded by highlighting the
      feasibility of using highly treated recycled water for existing and new washing
      machines. This could provide a powerful guidance for sustainable water reuse
      management in the long term. However, more detailed field trials and
      investigations are still needed to effectively understand, predict and manage the
      impact of selected recycled water for new end use alternatives.

PMID- 22964403
TI  - Letter from the guest editor: orbital and ear, nose, and throat emergencies.

PMID- 22964404
TI  - Orbital fractures: role of imaging.
AB  - The orbit may be injured directly or indirectly. Blunt and penetrating trauma
      occurs with equal frequency. Soft tissue swelling often obscures direct clinical
      evaluation of the globe, limits ocular motion, and may limit clinical assessment
      of vision. Plain film radiographs of the orbits and sinuses are rarely used for
      diagnosis in orbital trauma. Computed tomography is considered the imaging
      modality of choice in this circumstance, as it is deemed to be the most accurate
      method in detecting fractures. The protocol is based on obtaining thin-section
      axial scans and multiplanar reformatted images, both are useful tools to guide
      treatment. Orbital fractures are not considered an ophthalmologic emergency
      unless there is visual impairment or globe injury. Surgical repair is indicated
      for patients who have persistent diplopia or cosmetic concerns (enophthalmos) and
      generaly is not performed until swelling subsides 7-10 days after injury.

PMID- 22964405
TI  - Role of computed tomography in the assessment of intraorbital foreign bodies.
AB  - Intraorbital foreign bodies (IOFBs) are a common occurrence worldwide and happen
      at a frequency of once in every 6 cases of orbital trauma. An orbital foreign
      body may produce a variety of signs and symptoms related to its size,
      composition, and ballistics. Retained foreign bodies may give rise to cellulitis,
      abscess, fistulas, and impaired vision and motility. Prompt detection and
      accurate localization of IOFBs are essential for the optimum management of
      patients, to enable the surgeon to plan the most atraumatic method of removing
      the IOFB. Computed tomography (CT) is very useful in determining the size of
      foreign bodies and localizing them as intraocular, extraocular, or retro-ocular.
      CT is generally considered the gold standard in the evaluation of IOFBs because
      it is safe to use with metallic IOFBs, excludes orbitocranial extension, and is
      also able to diagnose orbital wall fractures and orbital sepsis with high
      accuracy. Other potential complications excludible by CT are abscess formation in
      the orbit, bone, and brain. Magnetic resonance imaging is generally not
      recommended for the evaluation of the foreign bodies because of risks associated
      with magnetic metal.

PMID- 22964406
TI  - Imaging evaluation of facial complex strut fractures.
AB  - High-resolution multidetector computed tomography with multiplanar reformations
      and 3-D postprocessing often provides the detail necessary for preoperative
      assessment of facial injuries. Maxillofacial fractures are classified in the
      following manner: upper face fractures, midface fractures (the most frequent), Le
      Fort fractures, and lower face or mandible fractures. The facial skeleton is a
      framework of vertical and horizontal buttresses that ensures a better resistance
      to trauma, but serves also as reference for maxillofacial surgery to restore
      facial size and shape. Radiologists should know how to diagnose and report the
      main types of facial fracture.

PMID- 22964407
TI  - Multidetector computed tomography of maxillofacial fractures: the key to high
      impact radiological reporting.
AB  - Maxillofacial fractures are very common. Recognizing patterns of facial fractures
      is helpful in assessing maxillofacial injury and accurately characterizing all
      fractures that may be present. Facial fractures are grouped into the following
      categories: nasal bone, naso-orbito-ethmoid, orbital, zygomatic, maxillary
      (including Le Fort-type fractures), mandibular, and frontal sinus fractures.
      Within each subgroup of facial fractures, there are key findings, whether of the
      fracture itself or of potential associated injuries, that are important factors
      in determining whether the patient is managed conservatively or with surgery.
      This article highlights the features of facial fractures that are the most
      important to the surgeons and provides a framework for effective radiological
      reporting.

PMID- 22964408
TI  - Multidetector CT of temporal bone fractures.
AB  - Temporal bone fracture is a relatively common finding among trauma patients.
      Before the development of high-resolution multidetector computed tomography
      (MDCT) imaging, fractures of the skull base and temporal bone were a challenge to
      diagnose clinically. With current imaging technology, most such fractures are
      easily detected, and the challenge now lies in predicting the severity of injury
      and possible complications. In this review, we discuss the detection and
      classification of temporal bone fractures, their distinction from
      pseudofractures, and the role of imaging in establishing prognosis, particularly
      with respect to complications.

PMID- 22964409
TI  - Emergency imaging assessment of deep neck space infections.
AB  - Deep neck space infection may lead to severe and potentially life-threatening
      complications, such as airway obstruction, mediastinitis, septic embolization,
      dural sinus thrombosis, and intracranial abscess. The clinical presentation is
      widely variable, and often early symptoms do not reflect the disease severity.
      The complication risk depends on the extent and anatomical site: diseases that
      transgress fascial boundaries and spread along vertically oriented spaces
      (parapharyngeal, retropharyngeal, and paravertebral space) have a higher risk of
      complications and require a more aggressive treatment compared with those
      confined within a nonvertically oriented space (peritonsillar, sublingual,
      submandibular, parotid, and masticator space). Imaging has 5 crucial roles: (1)
      confirm the suspected clinical diagnosis, (2) define the precise extent of the
      disease, (3) identify complications, (4) distinguish between drainable abscesses
      and cellulitis, and (5) monitor deep neck space infection progression.
      Ultrasonography is the gold standard to differentiate abscesses from cellulitis,
      for the diagnosis of lymphadenitis. and to identify internal jugular
      thrombophlebitis in the infrahyoid neck. However, field-of-view limitation and
      poor anatomical information confine the use of ultrasonography to the evaluation
      of superficial lesions and to image-guided aspiration or drainage. Computed
      tomography (CT) combines fast image acquisition and precise anatomical
      information without field-of-view limitations. For these reasons, it is the most
      reliable technique for the evaluation of deep and multicompartment lesions and
      for the identification of mediastinal and intracranial complications. Contrast
      agent administration enhances the capability to differentiate fluid collections
      from cellulitis and allows the detection of vascular complications. Magnetic
      resonance imaging is more time-consuming than CT, limiting its use to selected
      indications. It is the technique of choice for assessing the epidural space
      involvement in pre- and paravertebral space infections and complements CT in the
      evaluation of the infections reaching the skull base.

PMID- 22964410
TI  - Neck neoplastic conditions in the emergency setting: role of multidetector
      computed tomography.
AB  - Emergent conditions resulting from head and neck neoplasms and their treatment
      include acute airway obstruction, hemorrhage, spinal cord compression, bilateral
      vocal cord paralysis, and septic thrombophlebitis. These conditions require
      accurate diagnosis and rapid intervention to avoid severe permanent damage or
      death. Successful treatment requires a coordinated response by emergency medicine
      physicians, otolaryngologists, vascular surgeons, and radiologists. We review
      these head and neck oncological conditions, which present emergently, with a
      focus on radiological evaluation and interpretation.

PMID- 22964411
TI  - Emergency pediatric ear, nose, and throat imaging.
AB  - Pediatric ear, nose, and throat emergencies broadly comprise infection, trauma,
      and airway obstruction secondary to a multitude of etiologies. Imaging occupies
      center stage in the diagnosis of many of these conditions and their
      complications, making it imperative for radiologists and other physicians
      covering the pediatric emergency department to familiarize themselves with the
      imaging appearances of these entities. Toward this goal, this article describes
      the imaging features of common pediatric ear, nose, and throat emergencies.
      Differential considerations, potential fallacies, and complications have been
      discussed when appropriate. Because a sound knowledge of the most relevant,
      efficient, time, and cost-effective imaging modality is of undisputable value in
      the acute setting, the preferred modality for each specific condition has been
      outlined. Finally, in alignment with our commitment to using radiation
      judiciously, we have suggested using ultrasonography and magnetic resonance
      instead of computed tomography, where possible, to optimize cost-benefit ratio
      for our young patients.

PMID- 22964412
TI  - Role of imaging in the assessment of impacted foreign bodies in the hypopharynx
      and cervical esophagus.
AB  - Impaction of foreign bodies in the upper digestive tract is a serious pathologic
      condition in ear, nose, and throat practice and is particularly common in
      children, prisoners, and psychiatric patients. Commonly found objects include
      fish bones, chicken bones, pieces of glass, dental prostheses, coins, and
      needles. The goals of the initial patient assessment are to identify the type of
      object, its location in the gastrointestinal tract, the presence of any
      associated complications, and the presence of any underlying esophageal
      conditions. Radiographic evaluation is helpful to confirm the location of foreign
      bodies and associated complications. Plain films of the neck and chest commonly
      will show the location of radiopaque objects, such as coins. Both anteroposterior
      and lateral views are necessary, as some radiopaque objects overlying the
      vertebral column may only be visible on the lateral view. Multidetector row
      computed tomography is superior to plain radiographs for the detection of
      pharyngoesophageal foreign bodies and provide additional crucial information for
      the management of complicated cases especially related to sharp or pointed
      ingested foreign bodies.

PMID- 22964413
TI  - Coffee and tea consumption and risk of lung cancer: a dose-response analysis of
      observational studies.
AB  - Results from the recent meta-analysis suggested a favorable effect of green tea
      consumption and risk of lung cancer, while no significant association was found
      between black tea consumption and risk of lung cancer. Besides, a significantly
      positive association was found between coffee consumption and risk of lung
      cancer. However, the relationship of green tea and coffee consumption is unclear.
      Thus the dose-response relationship was assessed by restricted cubic spline model
      and multivariate random-effect meta-regression. Results suggested that a linear
      dose-response relationship exists between coffee consumption and risk of lung
      cancer, while the dose-response relationship is nonlinear between green tea
      consumption and risk of lung cancer.

PMID- 22964414
TI  - Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts
      by activation of Notch signaling.
AB  - Postnatal bone marrow contains mesenchymal stem cells (MSCs) that are osteoblast
      precursors with great therapeutic potential. The oxygen tension in bone marrow is
      about 1-7% pO2 which is much lower than that of the external environment. The
      effect of these hypoxic conditions on MSC differentiation is not fully
      understood. In this study, we show that hypoxia inhibits osteogenic
      differentiation of MSCs, and that this effect is associated with increased levels
      of Notch1 and increased activity of Notch signaling. Knockdown of Notch1 in MSCs
      by shRNA markedly rescues the impaired osteogenic differentiation of MSCs.
      Furthermore, Notch1 physiologically binds to Runx2 and inhibits its
      transcriptional activity. Thus, hypoxia inhibits MSC differentiation into
      osteoblasts by activating the Notch pathway.

PMID- 22964415
TI  - Unravelling the evolution of neural stem cells in arthropods: notch signalling in
      neural stem cell development in the crustacean Daphnia magna.
AB  - The genetic regulatory networks controlling major developmental processes seem to
      be conserved in bilaterians regardless of an independent or a common origin of
      the structures. This has been explained by the employment of a genetic toolkit
      that was repeatedly used during bilaterian evolution to build the various forms
      and body plans. However, it is not clear how genetic networks were incorporated
      into the formation of novel structures and how homologous genes can regulate the
      disparate morphological processes. Here we address this question by analysing the
      role of Notch signalling, which is part of the bilaterian toolkit, in neural stem
      cell evolution in arthropods. Within arthropods neural stem cells have evolved in
      the last common ancestor of insects and crustaceans (Tetraconata). We analyse
      here for the first time the role of Notch signalling in a crustacean, the
      branchiopod Daphnia magna, and show that it is required in neural stem cells for
      regulating the time of neural precursor production and for binary cell fate
      decisions in the ventral neuroectoderm. The function of Notch signalling has
      diverged in the ventral neuroectoderm of insects and crustaceans accompanied by
      changes in the morphogenetic processes. In the crustacean, Notch controlled
      mechanisms of neuroblast regulation have evolved that are surprisingly similar to
      vertebrates and thus present a remarkable case of parallel evolution. These new
      data on a representative of crustaceans complete the arthropod data set on Notch
      signalling in the nervous system and allow for reconstructing how the Notch
      signalling pathway has been co-opted from pre-existing structures to the
      development of the evolving neural stem cells in the Tetraconata ancestor.

PMID- 22964417
TI  - mRNA splicing in trypanosomes.
AB  - The parasitic unicellular trypanosomatids are responsible for several fatal
      diseases in humans and livestock. Regarding their biochemistry and molecular
      biology, they possess a multitude of special features such as polycistronic
      transcription of protein-coding genes. The resulting long primary transcripts
      need to be processed by coupled trans-splicing and polyadenylation reactions,
      thereby generating mature mRNAs. Catalyzed by a large ribonucleoprotein complex
      termed the spliceosome, trans-splicing attaches a 39-nucleotide leader sequence,
      which is derived from the Spliced Leader (SL) RNA, to each protein-coding gene.
      Recent genome-wide studies demonstrated that alternative trans-splicing increases
      mRNA and protein diversity in these organisms. In this mini-review we give an
      overview of the current state of research on trans-splicing.

PMID- 22964416
TI  - Notch signaling differentially regulates the cell fate of early endocrine
      precursor cells and their maturing descendants in the mouse pancreas and
      intestine.
AB  - Notch signaling inhibits differentiation of endocrine cells in the pancreas and
      intestine. In a number of cases, the observed inhibition occurred with Notch
      activation in multipotential cells, prior to the initiation of endocrine
      differentiation. It has not been established how direct activation of Notch in
      endocrine precursor cells affects their subsequent cell fate. Using conditional
      activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the
      effects of Notch in both organs, on cell fate of early endocrine precursors and
      maturing endocrine-restricted cells, respectively. Notch did not preclude the
      differentiation of a limited number of endocrine cells in either organ when
      activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+)
      cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+)
      cells, Notch favored enterocyte and goblet cell fates, while selecting against
      endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells
      in the pancreas retain plasticity to respond to Notch, giving rise to intraislet
      ductules as well as cells with no detectable pancreatic lineage markers that
      appear to have limited ultrastructural features of both endocrine and duct cells.
      These results suggest that Notch directly regulates cell fate decisions in
      multipotential early endocrine precursor cells. Some maturing endocrine
      restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in
      response to Notch, indicating previously unappreciated plasticity at such a late
      stage of endocrine differentiation.

PMID- 22964418
TI  - Combined interaction of multi-locus genetic polymorphisms in cytarabine
      arabinoside metabolic pathway on clinical outcomes in adult acute myeloid
      leukaemia (AML) patients.
AB  - Cytarabine arabinoside (ara-C) is the key agent for treating acute myeloid
      leukaemia (AML). Here, we genotyped 139 single nucleotide polymorphisms (SNPs)
      within the ara-C transport and metabolic pathway using the Illumina Golden Gate
      Assay in 97 patients with previously non-treated de novo AML other than M3. DCK
      rs4694362 (CC genotype) was a significant poor prognostic factor for overall
      survival (OS) (hazard ratio [HR], 33.202 [95% confidence interval (CI), 4.937
      223.273], P<0.0001, P(Bonferroni)=0.017). SLC29A1 rs3734703 (AA or AC genotype)
      in combination with TYMS rs2612100 (AA genotype) was significantly associated
      with shorter relapse free survival (RFS) (HR, 17.630 [95% CI, 4.829-64.369],
      P<0.0001, P(Bonferroni)=0.021). These SNPs showed moderate or large inter ethnic
      divergence in allele frequencies from African or Caucasian populations. The
      results of our study suggest that a single SNP and SNP-SNP interactions may help
      to predict the drug response and provide a guide in developing individualised
      chemotherapy for AML patients receiving ara-C based chemotherapy.

PMID- 22964419
TI  - The growth and electronic structure of azobenzene-based functional molecules on
      layered crystals.
AB  - In situ ultraviolet photoelectron spectroscopy is used to study the growth of
      ultrathin films of azobenzene-based functional molecules (azobenzene, Disperse
      Orange 3 and a triazatriangulenium platform with an attached functional azo
      group) on the layered metal TiTe(2) and on the layered semiconductor HfS(2) at
      liquid nitrogen temperatures. Effects of intermolecular interactions, of the
      substrate electronic structure, and of the thermal energy of the sublimated
      molecules on the growth process and on the adsorbate electronic structure are
      identified and discussed. A weak adsorbate-substrate interaction is particularly
      observed for the layered semiconducting substrate, holding the promise of
      efficient molecular photoswitching.

PMID- 22964420
TI  - Cerebral hemodynamic changes at basilar artery in obstructive sleep apnea
      syndrome after continuous positive airway pressure treatment.
AB  - BACKGROUND: Cerebral vasoreactivity in obstructive sleep apnea syndrome is
      altered. Continuous positive airway pressure is effective in the reduction of the
      occurrence of apneas. We studied whether this treatment also improves cerebral
      vasoreactivity. METHODS: The breath-holding maneuver was performed and assessed
      by apnea test with transcranial Doppler in the basilar artery. After 2 years of
      continuous positive airway pressure treatment, the test was repeated. RESULTS:
      There is an improvement in the apnea test after continuous positive airway
      pressure. There are increases in the pulsatility index, diastolic blood pressure,
      and basal heart rate. The improvement in the apnea test depends on the body mass
      index of the patient. CONCLUSIONS: Cerebral vasoreactivity as measured by the
      apnea test improves after 2 years of continuous positive airway pressure. This
      improvement depends of the body mass index of the patient.

PMID- 22964421
TI  - Severe envenomation by Cerastes cerastes viper: an unusual mechanism of acute
      ischemic stroke.
AB  - Cerebral complications after snake bites--particularly ischemic complications-
      are rare. Very few cases of cerebral infarction resulting from a viper bite have
      been reported, and we call attention to this uncommon etiology. We discuss 3
      authenticated reports of acute ischemic cerebrovascular accidents after 3 typical
      severe envenomations by Cerastes cerastes vipers. The 3 patients developed
      extensive local swelling and life-threatening systemic envenomation characterized
      by disseminated intravascular coagulopathy, increased fibrinolysis,
      thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure.
      This clinical picture involved atypical neurologic manifestations. These patients
      had either low Glasgow Coma Scale (GCS) or hemiparesis within hours to 4 days
      after being bitten, and they were found to have computed tomographic evidence of
      single or multiple ischemic (nonhemorrhagic) strokes of small- to large-vessel
      territories of the brain. One patient had good clinical recovery without
      neurologic deficits. Thrombotic complications occurred an average of 36 hours
      after being bitten, and their importance depends on the degree of envenomation.
      The possible mechanisms for cerebral infarction in these cases include
      generalized prothrombotic action of the venom (consumptive coagulopathy), toxin
      induced vasculitis, and endothelial damage.

PMID- 22964422
TI  - Vibrio aestivus sp. nov. and Vibrio quintilis sp. nov., related to Marisflavi and
      Gazogenes clades, respectively.
AB  - Two new Vibrio species, Vibrio aestivus and Vibrio quintilis, are described after
      a polyphasic characterization of strains M22(T), M61 and M62(T), isolated from
      seawater collected off a beach on the East coast of Spain (Valencia). All three
      strains are Gram negative, mesophilic, slightly halophilic, fermentative rods. V.
      aestivus (M22(T)=CECT 7558(T)=CAIM 1861(T)=KCTC 23860(T) and M61=CECT 7559=CAIM
      1862=KCTC 23861) is oxidase positive, reduces nitrates to nitrites, is negative
      for Voges Proskauer, arginine dihydrolase and indole and non hydrolytic on most
      substrates tested. The 16S rRNA gene sequences of M22(T) and M61 are most similar
      to Vibrio marisflavi (97.1-97.2%) but phylogenetic analysis using NJ, MP and ML
      methods display Vibrio stylophorae (96.2% similarity) as sibling species. The
      three species form a deep clade in the genus Vibrio. Average Nucleotide Identity
      (ANI) values, determined as a measure of overall genomic resemblance, confirmed
      that strains M22(T) and M61 are members of the same species, different to V.
      marisflavi CECT 7928(T). V. quintilis (M62(T)=CECT 7734(T)=CAIM 1863(T)=KCTC
      23833(T)) is aerogenic, arginine dihydrolase and Voges Proskauer positive,
      oxidase negative and unable to reduce nitrate, traits shared by most species in
      the Gazogenes clade. It is unpigmented and does not grow on TCBS Agar. 16S rRNA
      gene similarities to its nearest species, Vibrio aerogenes and Vibrio mangrovi,
      are 97.6% and 96.0% respectively. Strain M62(T) and V. aerogenes CECT 7868(T)
      display ANI values well below the 95% boundary for genomic species.

PMID- 22964423
TI  - Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide
      and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of
      aldo-keto reductases.
AB  - Reactive oxygen species (ROS) and consequent aldehydic lipid peroxidation
      products have been identified as significant in the progression of
      neurodegenerative diseases such as Alzheimer's and Parkinson's. Understanding and
      enhancing endogenous cellular protection against oxidants and aldehydes is
      therefore of interest in developing strategies to combat these diseases. In this
      study the role of the aldo-keto reductases AKR7A2 and AKR1C3 in protecting human
      astrocytoma 1321N1 cells against oxidant and aldehyde toxicity was investigated
      using siRNA gene silencing. Results show that both enzymes are responsible for
      part of the intrinsic protection against aldehydes and oxidants. Treating cells
      with sub-lethal concentrations of oxidant or aldehyde stress or with the natural
      coumarin 7-hydroxycoumarin (umbelliferone) revealed that endogenous resistance to
      aldehydes and oxidants can be induced significantly. The basis of the inducible
      protection by 7-hydroxycoumarin was shown to be associated with induction of the
      aldo-keto reductases AKR7A2 (1.5-fold) and AKR1C (3-fold), and this inducible
      protection was sufficient to overcome siRNA silencing of AKR1C3. These results
      indicate the importance of AKR family members in the detoxication of aldehydes,
      and also show that the natural phytochemical 7-hydroxycoumarin is a potential
      therapeutic candidate for neurodegenerative diseases.

PMID- 22964424
TI  - Fusaric acid is a crucial factor in the disturbance of leaf water imbalance in
      Fusarium-infected banana plants.
AB  - Fusarium wilt of banana is caused by Fusarium oxysporum f. sp. cubense infection.
      The initial chlorosis symptoms occur progressively from lower to upper leaves,
      with wilt symptoms subsequently occurring in the whole plant. To determine the
      effect of the pathogen infection on the gas exchange characteristics and water
      content in banana leaves, hydroponic experiments with pathogen inoculation were
      conducted in a greenhouse. Compared with control plants, infected banana
      seedlings showed a higher leaf temperature as determined by thermal imaging.
      Reduced stomatal conductance (g(s)) and transpiration rate (E) in infected plants
      resulted in lower levels of water loss than in control plants. Water potential in
      heavily diseased plants (II) was significantly reduced and the E/g(s) ratio was
      higher than in noninfected plants, indicating the occurrence of uncontrolled
      water loss not regulated by stomata in diseased plants. As no pathogen colonies
      were detected from the infected plant leaves, the crude toxin was extracted from
      the pathogen culture and evaluated about the effect on banana plant to further
      investigate the probable reason of these physiological changes in Fusarium
      infected banana leaf. The phytotoxin fusaric acid (FA) was found in the crude
      toxin, and both crude toxin and pure FA had similar effects as the pathogen
      infection on the physiological changes in banana leaf. Additionally, FA was
      present at all positions in diseased plants and its concentration was positively
      correlated with the incidence of disease symptoms. Taken together, these
      observations indicated that FA secreted by the pathogen is an important factor
      involved in the disturbance of leaf temperature, resulting in uncontrolled leaf
      water loss and electrolyte leakage due to damaging the cell membrane. In
      conclusion, FA plays a critical role in accelerating the development of Fusarium
      wilt in banana plants by acting as a phytotoxin.

PMID- 22964426
TI  - Genotoxicity and development effects of brominated flame retardant PBDEs and UV
      exposed PBDEs on grass shrimp (Palaemonetes pugio) embryo.
AB  - To understand how polybrominated diphenyl ethers (PBDEs) affect the hatching
      sensitivity of grass shrimp embryos in different developmental stages, the
      hatching rates of embryos were measured after PBDE exposure on the early- and
      late-stage embryo of grass shrimp. PBDEs had no clear influence on the hatching
      rate. Also, to investigate on the reproductive and genetic toxicities of UV
      exposed PBDEs, the hatching rate and DNA damage of stage 7 embryos were also
      measured. PBDEs had no significant impact on the hatching rate and DNA damage of
      grass shrimp in most experimental conditions regardless of embryo developmental
      stage or UV exposure, but in the case of UV-exposed BDE-47, the hatching rate was
      decreased, suggesting a potential reproductive toxicity. This research is
      meaningful because it is the first study to propose that PBDEs can cause
      reproductive toxicity in marine organism, after flowing into the ocean and
      undergoing photochemical reactions stimulated by UV.

PMID- 22964427
TI  - Are baleen whales exposed to the threat of microplastics? A case study of the
      Mediterranean fin whale (Balaenoptera physalus).
AB  - Baleen whales are potentially exposed to micro-litter ingestion as a result of
      their filter-feeding activity. However, the impacts of microplastics on baleen
      whales are largely unknown. In this case study of the Mediterranean fin whale
      (Balaenoptera physalus), we explore the toxicological effects of microplastics on
      mysticetes. The study included the following three steps: (1) the
      collection/count of microplastics in the Pelagos Sanctuary (Mediterranean Sea),
      (2) the detection of phthalates in surface neustonic/planktonic samples, and (3)
      the detection of phthalates in stranded fin whales. A total of 56% of the surface
      neustonic/planktonic samples contained microplastic particles. The highest
      abundance of microplastics (9.63 items/m(3)) was found in the Portofino MPA
      (Ligurian Sea). High concentrations of phthalates (DEHP and MEHP) were detected
      in the neustonic/planktonic samples. The concentrations of MEHP found in the
      blubber of stranded fin whales suggested that phthalates could serve as a tracer
      of the intake of microplastics. The results of this study represent the first
      warning of this emerging threat to baleen whales.

PMID- 22964428
TI  - Ring test evaluation of the repeatability and reproducibility of a Porcine
      reproductive and respiratory syndrome virus oral fluid antibody enzyme-linked
      immunosorbent assay.
AB  - The precision of a Porcine reproductive and respiratory syndrome virus (PRRSV)
      oral fluid antibody enzyme-linked immunosorbent assay (ELISA) was evaluated by
      calculating reliability coefficients for assay repeatability (within laboratory)
      and assay reproducibility (between laboratories). Randomly ordered oral fluid
      samples of known (n = 39) and unknown (n = 224) PRRSV antibody status were tested
      in 12 diagnostic laboratories. Each laboratory tested the samples twice, first
      using an antibody ELISA kit and reagents provided to them (phase 1) and then
      using an ELISA kit and reagents configured in their respective laboratory (phase
      2). Repeatability (within laboratory) reliability coefficients calculated using
      results from samples of known PRRSV antibody status ranged from 0.724 to 0.997 in
      phase 1 and from 0.953 to 0.998 in phase 2. Reproducibility (between
      laboratories) reliability coefficients were calculated for 3 conditions: case 1-
      samples of unknown status (n = 224); case 2--samples of known status (n = 39),
      and case 3--all samples (n = 263). Among the 3 cases, reliability coefficients
      ranged from 0.937 to 0.964 in phase 1 and from 0.922 to 0.935 in phase 2. For
      case 3, it was estimated that 96.67% of the total variation in phase 1 and 93.21%
      in phase 2 could be attributed to the oral fluid samples themselves. Overall, the
      PRRSV oral fluid antibody ELISA was highly repeatable and reproducible. The
      current study supports the routine use of this test in laboratories providing
      diagnostic service to pig producers.

PMID- 22964429
TI  - Hepatocellular carcinomas in Vietnamese pot-bellied pigs (Sus scrofa).
AB  - Various neoplasms have been reported in Vietnamese pot-bellied pigs (Sus scrofa)
      with few reports of hepatocellular tumors. Twenty-two pot-bellied pigs diagnosed
      with hepatocellular carcinoma at necropsy over a 3-year period at one institution
      are described, representing 29% of the total pot-bellied pigs necropsied. The
      average age of affected pigs was 16.6 years with 15 males and 7 females. The most
      common clinical signs were decreased appetite (16/22) and weight loss (7/22).
      Grossly, the majority were massive tumors (13/22) with fewer nodular tumors
      (8/22) and 1 diffuse tumor. Massive tumors were typically multilobulated, very
      large, and encompassing 1 or more adjacent liver lobes, and were soft to firm and
      tan-yellow to orange-brown. Nodular tumors had multiple, 1-15 cm in diameter,
      discrete nodules in multiple liver lobes. Gross evidence of abscesses, necrosis,
      hemorrhage, or cysts associated with the tumor was occasionally described. Half
      of the cases had possible intrahepatic metastasis, and extrahepatic metastasis
      was identified in 3 cases, including to the hepatic lymph node (1/3), lung (2/3),
      spleen (1/3), and kidney (1/3). Histologically, all tumors had a trabecular or
      solid pattern, or a combination. An adenoid pattern was only identified in small
      regions of a few tumors. The neoplastic cells were relatively well-differentiated
      with moderate pleomorphism and a low mitotic index. Other histologic features
      within the tumors included intracellular glycogen or lipid accumulation,
      extramedullary hematopoiesis, foci of coagulative necrosis, and bile stasis. Aged
      pot-bellied pigs can be predisposed to hepatocellular carcinomas, which are
      locally aggressive and can metastasize within the liver and to other organs.

PMID- 22964430
TI  - A case of feline neurolymphomatosis: pathological and molecular investigations.
AB  - Neurolymphomatosis is a very rare form of nervous system infiltration by lymphoma
      that can affect cranial and peripheral nerves and spinal nerve roots. The
      clinical appearance can mimic autoimmune or paraneoplastic neuropathies. To date,
      only 2 cases of neurolymphomatosis have been reported in the veterinary
      literature (1 dog and 1 cat). A case of neurolymphomatosis in a 5-year-old female
      Domestic Shorthair cat is reported. Two, whitish, bosselated, non-symmetric
      masses (1 cm * 1.2 cm * 0.5 cm) that incorporated almost all cranial nerves and
      semilunar ganglia occupying the basisphenoid depression were histologically
      composed of a proliferation of monomorphic lymphocytes. These lymphoid cells were
      positive for CD3 (T-cell lymphoma). Nested polymerase chain reaction detected
      feline leukemia provirus. Fragment analysis of feline T-cell receptor (TCR) gene
      rearrangements evidenced an oligoclonal pattern with few peaks of similar height.
      The integration of pathologic with biomolecular findings adds to the information
      concerning the role of Feline leukemia virus on TCRgamma rearrangements in cases
      of feline lymphoma.

PMID- 22964425
TI  - Immunoconjugates and long circulating systems: origins, current state of the art
      and future directions.
AB  - Significant progress has been made recently in the area of immunoconjugated drugs
      and drug delivery systems (DDS). The immuno-modification of either the drug or
      DDS has proven to be a very promising approach that has significantly improved
      the targeted accumulation in pathological sites while decreasing its undesirable
      side effects in healthy tissues. The arrangement for both prolonged life in the
      circulation and specific target recognition represents another potent strategy in
      the development of immuno-targeted systems. The longevity of immuno-targeted DDS
      such as immunoliposomes and immunomicelles improves their targetability even in
      the presence of the additional passive accumulation in areas with a compromised
      vasculature. The added use of the immuno-targeted systems takes advantage of the
      specific microenvironment of pathological sites including lowered pH, increased
      temperature, and variation in the enzymatic activity. "Smart" stimulus-responsive
      systems combine different valuable functionalities including PEG-protection,
      targeting antibody, cell-penetration, and stimulus-sensitive functions. In this
      review we examined the evolution, current status and future directions in the
      area of therapeutical immunoconjugates and long-circulating immuno-targeted DDS.

PMID- 22964431
TI  - The lymphotactin receptor is expressed in epithelial ovarian carcinoma and
      contributes to cell migration and proliferation.
AB  - Chemokine receptor-ligand interactions are important to support functioning of
      both normal and pathologic cells. The expression and function of chemokine
      receptors in epithelial ovarian carcinoma (EOC) is largely unknown. Here, we
      report that the lymphotactin receptor (XCR1) was expressed in primary and
      metastatic human epithelial ovarian carcinoma (EOC) specimens and cell lines. In
      contrast, expression of XCR1 was not detected in the normal ovary or in human
      normal ovarian surface epithelial cells. Our data indicate that XCL1 and XCL2 are
      either present in the malignant ascites or expressed by the ovarian carcinoma
      cells. The addition of lymphotactin (XCL1 and XCL2) stimulated migration and
      proliferation of XCR1-positive cells. Reduction of XCR1 expression in ovarian
      carcinoma cell line SKOV-3 resulted in abrogated diaphragm and peritoneal wall
      tumor formation and in reduced frequency of colonic, splenetic, and liver nodules
      in an in vivo xenograft mouse model. Taken together, our data suggest that XCR1
      is expressed early during the course of tumorigenic transformation and
      contributes towards increased cell migration and proliferation, which can
      facilitate the prometastatic behavior of EOC cells.

PMID- 22964432
TI  - Roles of estrogen receptor and p21(Waf1) in bortezomib-induced growth inhibition
      in human breast cancer cells.
AB  - Proteasome inhibitors such as bortezomib constitute novel therapeutic agents that
      are currently in clinical use and in clinical trials. In some neoplasms, cyclin
      dependent kinase inhibitors (CKI) such as p21(WAF1) have been proposed as key
      targets of proteasome inhibitors. p21(WAF1) expression can be modulated by p53, a
      tumor suppressor, and especially in breast cancer cells, by estrogen receptor
      alpha (ERalpha), which is highly relevant to cancer growth. We investigated the
      effects of bortezomib using a panel of six cancer cell lines with variable status
      of ERalpha or p53 and found that bortezomib inhibited the growth of all cell
      lines in the same concentration range irrespective of the ERalpha expression or
      the mutational status of p53. Bortezomib treatment significantly enhanced
      p21(WAF1) protein levels in all cell lines but with different mechanisms
      according to ERalpha status. In ERalpha-positive cells, bortezomib treatment
      caused a strong increase in p21(WAF1) mRNA, whereas in ERalpha-negative cells it
      predominantly enhanced p21(WAF1) protein levels suggesting a posttranslational
      mechanism of p21(WAF1) regulation in the ERalpha-negative cells. Moreover, the
      antiproliferative activity of bortezomib was prevented by ERalpha silencing or
      p21(WAF1) knockdown in ERalpha-positive cells. Collectively, our results
      highlight the potential roles of ERalpha and p21(WAF1) in growth inhibition of
      cancer cells mediated by proteasome inhibitors, such as bortezomib.

PMID- 22964434
TI  - Effect of subthalamic deep brain stimulation on pain in Parkinson's disease.
AB  - Painful sensations are common in Parkinson's disease. In many patients, such
      sensations correspond to neuropathic pain and could be related to central
      alterations of pain processing. Subthalamic nuclei deep brain stimulation
      improves motor function in Parkinson's disease. Several structures of the basal
      ganglia are involved in nociceptive function, and deep brain stimulation could
      thus also modify pain perception in Parkinson's disease. To test this hypothesis,
      we compared subjective heat pain thresholds, in deep brain stimulation OFF and ON
      conditions in 2 groups of Parkinson's disease patients with or without
      neuropathic pain. We also compared pain-induced cerebral activations during
      experimental nociceptive stimulations using H(2)(15)O positron emission
      tomography in both deep brain stimulation OFF and ON conditions. Correlation
      analyses were performed between clinical and neuroimaging results. Deep brain
      stimulation significantly increased subjective heat pain threshold (from 40.3 +/-
      4.2 to 41.6 +/- 4.3, P=.03) and reduced pain-induced cerebral activity in the
      somatosensory cortex (BA 40) in patients with pain, whereas it had no effect in
      pain-free patients. There was a significant negative correlation in the deep
      brain stimulation OFF condition between pain threshold and pain-induced activity
      in the insula of patients who were pain free but not in those who had pain. There
      was a significant positive correlation between deep brain stimulation-induced
      changes in pain threshold and in pain-induced cerebral activations in the primary
      somatosensory cortex and insula of painful patients only. These results suggest
      that subthalamic nuclei deep brain stimulation raised pain thresholds in
      Parkinson's disease patients with pain and restored better functioning of the
      lateral discriminative pain system.

PMID- 22964433
TI  - SUZ12 promotes human epithelial ovarian cancer by suppressing apoptosis via
      silencing HRK.
AB  - Epithelial ovarian cancer (EOC) ranks first as the cause of death for
      gynecological cancers in the United States. SUZ12 is a component of the polycomb
      repressive complex 2 (PRC2) and is essential for PRC2-mediated gene silencing by
      generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3). The role
      of SUZ12 in EOC has never been investigated. Here, we show that SUZ12 is
      expressed at significantly higher levels in human EOC (n = 117) compared with
      either normal human ovarian surface epithelium (n = 35, P < 0.001) or fallopian
      tube epithelium (n = 15, P < 0.001). There is a positive correlation between
      expression of SUZ12 and EZH2 in human EOC (P < 0.001). In addition, expression of
      SUZ12 positively correlates with Ki67, a marker of cell proliferation (P <
      0.001), and predicts shorter overall survival (P = 0.0078). Notably, knockdown of
      SUZ12 suppresses the growth of human EOC cells in vitro and in vivo in both
      orthotopic and subcutaneous xenograft EOC models. In addition, SUZ12 knockdown
      decreases the levels of H3K27Me3 and triggers apoptosis of human EOC cells.
      Mechanistically, we identified Harakiri (HRK), a proapoptotic gene, as a novel
      SUZ12 target gene, and showed that HRK upregulation mediates apoptosis induced by
      SUZ12 knockdown in human EOC cells. In summary, we show that SUZ12 promotes the
      proliferation of human EOC cells by inhibiting apoptosis and HRK is a novel SUZ12
      target gene whose upregulation contributes to apoptosis induced by SUZ12
      knockdown.

PMID- 22964435
TI  - Cervical spinal cord injection of epidural corticosteroids: comprehensive
      longitudinal study including multiparametric magnetic resonance imaging.
AB  - Despite widespread use, the efficacy of epidural corticosteroid injections (ESI)
      for osteoarthritis-associated neck or radicular pain remains uncertain, so even
      rare serious complications enter into discussions about use. However, various
      factors impede investigation and publication of serious adverse events. To that
      end, we developed new magnetic resonance imaging (MRI) techniques for spinal cord
      white matter quantification and used the best available physiological tests to
      characterize a cervical spinal cord lesion caused by inadvertent intramedullary
      injection of Depo-Medrol. A 29-year-old woman with mild cervical osteoarthritis
      had 2 years of headache and neck pain (concussion and whiplash) after 2 minor
      motor vehicle accidents. During C5-6 ESI, she developed new left-sided motor and
      sensory symptoms, and MRI demonstrated a new left dorsal spinal cord cavity. Mild
      left-sided motor and sensory symptoms have persisted for more than 2.5 years,
      during which time we performed serial neurological examinations, standard
      electrodiagnostics, somatosensory evoked potentials, and transcranial measurement
      of corticospinal central motor conduction time (CMCT). We used 3-Tesla MRI with a
      32-channel coil developed for high-resolution cervical spinal cord structural
      imaging, diffusion tensor imaging (DTI), and magnetization transfer (MT). T(2)(*)
      weighted signal and DTI and MT metrics showed delayed spread of the lesion across
      4 vertebral levels rostrally, consistent with Wallerian degeneration within the
      ascending left dorsal columns. However, only CMCT metrics detected objective
      correlates of her left hemiparesis and bilateral hyperreflexia. DTI and MT
      metrics may better distinguish between post-traumatic demyelination and axonal
      degeneration than conventional MRI. These tests should be considered to better
      characterize similar spinal cord injuries.

PMID- 22964437
TI  - Sleep in children with autism spectrum disorder.
AB  - Children with autism spectrum disorder demonstrate an increased prevalence of
      difficulties with sleep initiation and maintenance. The consequences may include
      alterations in daytime behavior, memory, and learning in patients, and
      significant stress in caretakers. The dysregulation of melatonin synthesis,
      sensitization to environmental stimuli, behavioral insomnia syndromes, delayed
      sleep phase syndrome, rapid eye movement sleep behavior disorder, and comorbid
      anxiety, depression, and epilepsy comprise common etiologic factors. The clinical
      assessment of sleep problems in this population and a management algorithm are
      presented.

PMID- 22964436
TI  - Treatment of pediatric migraine in the emergency room.
AB  - Migraine constitutes a relatively common reason for pediatric emergency room
      visits. Given the paucity of randomized trials involving pediatric migraineurs in
      the emergency department setting compared with adults, recommendations for
      managing these children are largely extrapolated from adult migraine emergency
      room studies and trials involving outpatient home pediatric migraine therapy. We
      review current knowledge about pediatric migraineurs presenting at the emergency
      room and their management, and summarize the best evidence available to guide
      clinical decision-making.

PMID- 22964438
TI  - Antiglutamic acid decarboxylase antibodies in children with encephalitis and
      status epilepticus.
AB  - Encephalitis may present with seizures or status epilepticus, and the etiology is
      usually presumed. Specific antibodies to ion channels, receptors, and other
      synaptic proteins were identified during the past decade. However, only a few
      studies investigated antiglutamic acid decarboxylase antibodies and antibodies to
      cell membrane ion channels or surface antigens in pediatric encephalitis and
      status epilepticus. We examined antibodies to glutamic acid decarboxylase and
      cell membrane ion channels or surface antigens in acute-phase serum from 17
      children with encephalitis and status epilepticus. Antiglutamic acid
      decarboxylase antibody titers were compared with those of control children
      manifesting therapy-resistant epilepsy. Antiglutamic acid decarboxylase antibody
      titers were significantly higher in those with encephalitis and status
      epilepticus than in those with therapy-resistant epilepsy. No patient
      demonstrated antibodies to cell membrane ion channels or surface antigens. Six
      children exhibited positive antiglutamic acid decarboxylase antibodies. One child
      died, three manifested postencephalitic epilepsy with neurologic deficits, and
      two recovered well. Higher antiglutamic acid decarboxylase antibody titers were
      evident in the children with encephalitis and status epilepticus. Clinicians
      should be aware of the potential role of antiglutamic acid decarboxylase
      antibodies in children with encephalitis and status epilepticus.

PMID- 22964439
TI  - Initial characteristics of Kawasaki disease with cerebrospinal fluid pleocytosis
      in febrile infants.
AB  - To distinguish between febrile infants with cerebrospinal fluid pleocytosis who
      are finally diagnosed with Kawasaki disease and those with enterovirus meningitis
      poses a diagnostic challenge. We compared clinical and laboratory features at
      admission between two groups of infants, aged 30-90 days, to identify markers of
      Kawasaki disease that initially presented as cerebrospinal fluid pleocytosis.
      During a 2-year period, 100 patients exhibiting cerebrospinal fluid pleocytosis
      were studied, including six (6.0%) with Kawasaki disease and 30 (30.0%) with
      enterovirus meningitis. A longer duration of fever before admission (P < 0.01),
      higher absolute neutrophil count (P < 0.01), increased C-reactive protein level
      (P < 0.01), pyuria (P = 0.02), and less prominent cerebrospinal fluid pleocytosis
      (P = 0.01) were identified as initial features of infants finally diagnosed with
      Kawasaki disease. No significant differences were evident in white blood cell
      count; platelet count; levels of hemoglobin, alanine aminotransaminase, aspartate
      aminotransferase, albumin, and sodium; cerebrospinal fluid chemistry; or presence
      of a rash. Our observations may offer early indicators of Kawasaki disease for
      timely diagnoses in febrile infants with cerebrospinal fluid pleocytosis.

PMID- 22964441
TI  - Contribution of the corticospinal tract to motor impairment in spina bifida.
AB  - We aimed to disentangle the proportional contributions of upper and lower motor
      neuron dysfunction to motor impairment in children with spina bifida. We enrolled
      42 children (mean age, 11.2 years; standard deviation, 2.8 years) with spina
      bifida and 36 control children (mean age, 11.4 years; standard deviation, 2.6
      years). Motor impairment was graded to severity scales in children with spina
      bifida. We recorded motor evoked potentials after transcranial and lumbosacral
      magnetic stimulation and compound muscle action potentials after electric nerve
      stimulation. Regarding lower motor neuron function, severely impaired children
      with spina bifida demonstrated smaller compound muscle action potential areas and
      lumbosacral motor evoked potential areas than control children; mildly impaired
      children hardly differed from control children. Compound muscle action potential
      latencies and lumbosacral motor evoked potential latencies did not differ between
      children with spina bifida and control children. Regarding upper motor neuron
      function, children with spina bifida demonstrated smaller transcranial motor
      evoked potential areas and longer central motor conduction times than control
      children. The smallest motor evoked potential areas and longest central motor
      conduction times were observed in severely impaired children. In children with
      spina bifida, the contribution of upper motor neuron dysfunction to motor
      impairment is more considerable than expected from clinical neurologic
      examination.

PMID- 22964440
TI  - Arginase deficiency with new phenotype and a novel mutation: contemporary
      summary.
AB  - In areas without expanded newborn screening, instead of presenting neonatally,
      patients with arginase deficiency typically present with spastic paraplegia in
      early childhood. Diagnosis of this rare neurometabolic disease poses the first
      challenge because it is often misdiagnosed as cerebral palsy during initial
      stages. We describe arginase deficiency in a 20-year-old woman with spastic
      paraplegia, progressive dystonia, dementia, peripheral neuropathy, epilepsy,
      liver cirrhosis, and non-B/non-C hepatocellular carcinoma. A novel homozygous
      mutation NM_000045.2 (ARG1):c.673del (p.Arg225GlyfsX5) was detected. We suggest
      that all children presenting with progressive neurodegeneration or spastic
      paraplegia in the absence of risk factors for cerebral palsy should be screened
      for inborn errors of metabolism, including arginase deficiency. For monitoring
      urea cycle defects, noninvasive imaging screening for liver fibrosis and
      hepatocellular carcinoma can help ensure early detection, with potential
      treatment implications.

PMID- 22964442
TI  - Does a normalizing electroencephalogram in benign childhood epilepsy with
      centrotemporal spikes abort attention deficit hyperactivity disorder?
AB  - This retrospective study delineated the efficacy of antiepileptic drugs in
      preventing the need for methylphenidate in patients with benign childhood
      epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder.
      Seventeen patients were identified. A reduction of electroencephalogram
      pathologic activity by more than 50% was achieved in some patients with the
      antiepileptic drugs levetiracetam, sulthiame, lamotrigine, clobazam, and valproic
      acid. Complete normalization was achieved in two patients with sulthiame.
      Improvement in attention along with the reduction of pathologic
      electroencephalogram activity was observed in four patients, two with sulthiame,
      and one each with lamotrigine and levetiracetam (which was ceased because of
      suicidal tendencies). However, this improvement in attention was either temporary
      or not significant enough to discontinue methylphenidate. Methylphenidate was
      eventually prescribed to all patients.

PMID- 22964443
TI  - Long-term outcomes of epilepsy surgery in school-aged children with partial
      epilepsy.
AB  - The pediatric epileptic spectrum and seizure control in surgical patients have
      been defined in developed countries. However, corresponding data on school-aged
      children from developing countries are insufficient. We summarized epileptic
      surgical data from four centers in China, to compare surgical outcomes of school
      aged children with intractable partial epilepsy from China and those from
      developed countries, and introduce surgical candidate criteria. Data from 206
      children (aged 6-14 years) undergoing surgical resection for epilepsy between
      September 2001 and January 2007 were selected. Postoperative freedom from
      seizures was achieved in 173 cases (84.0%) at 1 year, 149 (72.3%) at 3 years, and
      139 (67.5%) at 5 years. Patients with focal magnetic resonance imaging
      abnormalities and a short history of seizure were most likely to become seizure
      free postoperatively. Those with preoperative low intelligence quotients who
      became seizure-free postoperatively achieved improvements in full memory
      quotients, intelligence quotients, and overall quality of life at 2 years.
      Significant differences were evident in mean changes of full intelligence
      quotient, full memory quotient, and overall quality of life between patients with
      preoperative low intelligence quotients who received corpus callosotomies and
      those with a normal preoperative intelligence quotient, and between seizure-free
      children and those with continual seizures.

PMID- 22964444
TI  - Atypical presentation of neuropsychiatric lupus with acanthosis nigricans.
AB  - Cutaneous manifestations are commonly observed in pediatric patients with
      systemic lupus erythematosus. Acanthosis nigricans, however, is rarely reported,
      and even less often in association with neuropsychiatric manifestations of lupus
      erythematosus. We describe a 9-year-old boy with acute behavioral and cognitive
      deterioration, combined with cutaneous, diffuse hyperpigmented and hyperkeratotic
      plaques. Cerebral magnetic resonance imaging revealed cortical atrophy and white
      matter abnormalities involving the fornix, corpus callosum, and parieto-occipital
      periventricular regions. The presence of progressive cognitive and behavioral
      deterioration, combined with abnormal white matter signals on magnetic resonance
      imaging, led us to suspect X-linked adrenoleukodystrophy. The subsequent
      development of systemic signs, together with positive serologic tests, confirmed
      the diagnosis of neuropsychiatric lupus with acanthosis nigricans. We review the
      literature on acanthosis nigricans in systemic lupus erythematosus and the value
      of magnetic resonance imaging in evaluating patients with neuropsychiatric
      systemic lupus.

PMID- 22964445
TI  - Transient subcortical high-signal lesions in Kawasaki syndrome.
AB  - Kawasaki syndrome is an acute systemic vasculitis in children. The
      pathophysiology of Kawasaki syndrome presumably involves vascular inflammation,
      causing plasma leakage from systemic microvessels. From 1-30% of patients with
      Kawasaki syndrome exhibit central nervous system involvement, e.g., aseptic
      meningitis, epileptic seizures, transient hemiplegia, facial palsy, ataxia,
      chorea, ischemia, hearing loss, abnormal vision, disturbed consciousness, and
      behavioral changes. Neuroradiologically, Kawasaki syndrome demonstrates subdural
      effusion, infarction, atrophy, and reversible splenial lesions on magnetic
      resonance imaging. A 25-month-old boy developed transient hypertension with
      generalized seizure in the subacute phase of Kawasaki syndrome. Fluid-attenuated
      inversion recovery imaging, performed 5 hours and 2 days postseizure, indicated
      subtle, subcortical, high-signal-intensity lesions. Acute transient hypertension
      in this patient may have triggered the onset of lesions because of the increased
      permeability of brain microvessels, attributable to systemic vasculitis in
      Kawasaki syndrome. To our knowledge, subcortical lesions in Kawasaki syndrome
      were not previously reported.

PMID- 22964446
TI  - Prolonged survival and serial magnetic resonance imaging/magnetic resonance
      spectroscopy changes in infantile Krabbe disease.
AB  - Krabbe disease may present during infancy, late infancy, or adulthood. Earlier
      onset disease is associated with shorter survival times. We present a case of
      infantile onset Krabbe disease with prolonged survival, initial intracranial
      optic nerves and optic chiasm hypertrophy, and serial changes on cranial magnetic
      resonance imaging and magnetic resonance spectroscopy.

PMID- 22964447
TI  - Phenotypic heterogeneity in consanguineous patients with a common CLN8 mutation.
AB  - The most heterogeneous subtype of neuronal ceroid lipofuscinosis comprises the
      late infantile variant, which, in addition to the classic CLN2, was reported in
      children with CLN5, CLN6, CLN7/MFSD8, and CLN8 genes. Patients with CLN8
      mutations usually present as the late-infantile-onset neuronal ceroid
      lipofuscinosis phenotype and are mostly Turkish and Italian, but three patients
      from Israel, Pakistan, and Germany were also reported. In 2007, we described the
      late infantile variant phenotype caused by a missense mutation at the CLN8 gene
      (763C>G). This child with rapidly progressive disease within 3 years lost his
      mobility and manifested dementia, seizures, and profound visual loss.
      Subsequently we identified two additional children in the same pedigree with the
      same mutation and a considerably milder phenotype. Six and 3 years, respectively,
      after their onset of signs, they do not manifest motor disabilities, their
      cognitive regression and visual deficit are less appreciable, and only one
      manifests epilepsy. The reason for this clinical heterogeneity is unclear,
      although the presence of additional unknown mutated regulatory genes or
      epigenetic factors may explain it.

PMID- 22964448
TI  - Idiopathic paroxysmal tonic upward gaze.
AB  - Paroxysmal tonic upward gaze constitutes a neuro-ophthalmologic syndrome
      characterized by episodes of sustained conjugate upward deviation of the eyes,
      normal horizontal gaze, and ataxia. Its pathogenesis is unknown, and the etiology
      is heterogeneous. The prognosis is variable. We present a case of "idiopathic
      paroxysmal tonic upward gaze" with a positive clinical course and spontaneous
      remission.

PMID- 22964449
TI  - Autonomic dysreflexia in acute disseminated encephalomyelitis.
AB  - Autonomic dysreflexia occurs in patients with spinal cord injury, and is
      characterized by unbalanced sympathetic discharge, precipitated by noxious
      stimuli from a site below the spinal cord lesion. An 11-year-old boy with acute
      disseminated encephalomyelitis and spinal cord involvement manifested episodes of
      intense flushing and sweating, confined to the head and neck region, and
      associated with hypertension and tachycardia. His signs improved after changing a
      partly blocked bladder catheter. The clinical features suggested autonomic
      dysreflexia. Early recognition of autonomic dysreflexia is important because
      removal of the trigger precipitating the event may be life-saving.

PMID- 22964450
TI  - Internal carotid artery stenosis as the sequela of a pseudoaneurysm after
      methicillin-resistant Staphylococcus aureus infection.
AB  - Pseudoaneurysm of the internal carotid artery is an extremely uncommon
      complication of pediatric deep neck space infections in the postantibiotic era,
      and poses a diagnostic challenge to clinicians. Early recognition and aggressive
      management are essential to prevent mortality and serious morbidity. We describe
      a pseudoaneurysm of the left internal carotid artery after a retropharyngeal
      abscess in an infant. The retropharyngeal abscess required surgical drainage, and
      the pseudoaneurysm was managed conservatively with antibiotic therapy. The
      patient developed 50% stenosis of the left internal carotid artery after
      recovery. Limited data are available about long-term outcomes of pseudoaneurysms
      of the internal carotid artery. During 7-year follow-up, she demonstrated no
      neurologic sequelae and normal development. Despite the left internal carotid
      artery stenosis, blood supply to the left cerebral hemisphere is well maintained
      through the circle of Willis. We highlight the importance of early recognition
      and aggressive management to avoid serious outcomes.

PMID- 22964451
TI  - Physical activity patterns and function 3 months after arthroscopic partial
      meniscectomy.
AB  - OBJECTIVES: To compare physical activity levels, subject-reported function, and
      knee strength in 21 arthroscopic partial meniscectomy (APM) patients (age 45.7
      (6.06) years, BMI 27.3 (5.96) female 60%) 3 months post-surgery with 21 healthy
      controls (age 43.6 (5.71) years, BMI 24.5(4.2) female 60%) matched at the cohort
      level for age, gender and BMI. DESIGN: Case control study. METHODS: Physical
      activity intensity, number of steps, and minutes spent in activity were
      objectively quantified using an accelerometer-based activity monitor worn for 7
      days. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and concentric
      quadriceps strength were used to evaluate function post-surgery. Differences in
      activity levels and functional outcomes between the APM and control participants
      were assessed using t-tests, while multiple linear regression was used to
      quantify the best predictors of physical activity. RESULTS: APM patients engaged
      in a similar duration of activity to controls (469.0 (128.39)min vs. 497.1
      (109.9)min), and take a similar number of steps per day (9227 (2977) vs. 10,383
      (3501), but performed their activity at lower levels of intensity than controls.
      Time spent in moderate (r(2)=0.19) and hard (r(2)=0.145) intensity physical
      activity was best predicted by the Symptoms sub-scale of the KOOS for both
      controls and APM patients. CONCLUSIONS: APM patients participate in similar
      levels of activity at lower intensities, but with reduced activity at higher
      intensities which is related to the presence of symptoms of knee osteoarthritis.

PMID- 22964452
TI  - Influence of carbohydrate on serum caffeine concentrations following caffeine
      ingestion.
AB  - OBJECTIVES: To examine the effect of a high carbohydrate meal on serum caffeine
      concentration following caffeine intake. DESIGN: Randomised, double-blind,
      crossover. METHODS: Fourteen healthy males randomly completed 4 trials, each
      separated by 5 days. Participants either remained fasted (on 2 occasions) or
      ingested a high carbohydrate meal (2.0gkg(-1) carbohydrate, 42.4+/-0.6kJkg(-1))
      prior to consuming either 6 or 9mgkg(-1) anhydrous caffeine. Venous blood was
      sampled for the analysis of serum caffeine at baseline and at 6 time-points over
      4h following caffeine intake. RESULTS: Peak caffeine concentration occurred 60min
      following ingestion for both the 6 and 9mgkg(-1) fasted (p<0.001) trials compared
      to 120 and 180min following ingestion for the 6 and 9mgkg(-1) fed trials,
      respectively (p<0.001). Peak concentration was greater in the 9mgkg(-1) fasted
      trial than the corresponding fed condition (70+/-9MUmolL(-1) and 56+/-6MUmolL(
      1), respectively) and both were greater than the 6mgkg(-1) conditions (44+/
      8MUmolL(-1) and 38+/-8MUmolL(-1) for 6mgkg(-1) fasted and fed, respectively).
      Area under the caffeine curve was significantly greater (p<0.001) in the 9mgkg(
      1) fasted trial (3262MUmolL(-1)h(-1)), whilst areas were lowest in the 6mgkg(-1)
      fed trial (1644MUmolL(-1)h(-1)). CONCLUSIONS: A high carbohydrate meal consumed
      prior to caffeine ingestion significantly reduced serum caffeine concentrations
      and delayed time to peak concentration. Differences in research findings between
      caffeine supplementation studies may, at least in part, be related to variations
      in postprandial timing of caffeine intake. The influence of postprandial timing
      should be considered when athletes consume caffeine with the aim of enhancing
      performance.

PMID- 22964453
TI  - Feelings of control restore distorted time perception of emotionally charged
      events.
AB  - Humans perceive time with millisecond precision. However, when experiencing
      negative or fearful events, time appears to slow down and aversive events are
      judged to last longer than neutral or positive events of equal duration. Feelings
      of control have been shown to attenuate increases in arousal triggered by anxiety
      provoking events. Here, we tested whether feelings of control can go as far as
      influencing people's perception of the world, by modulating the perceived
      duration of aversive events. Observers judged the duration of images depicting
      positive or negative content, and we manipulated the amount of control
      experienced by participants. Crucially, participants never had any real control
      over events. All control was illusory. Results showed that when participants
      experienced low levels of control, negative images were judged as lasting longer
      than positive images. However, when participants illusorily experienced high
      levels of control, they no longer experienced aversive negative images as lasting
      longer than positive images.

PMID- 22964454
TI  - Priming effects under correct change detection and change blindness.
AB  - In three experiments, we investigated the priming effects induced by an image
      change on a successive animate/inanimate decision task. We studied both
      perceptual (Experiments 1 and 2) and conceptual (Experiment 3) priming effects,
      under correct change detection and change blindness (CB). Under correct change
      detection, we found larger positive priming effects on congruent trials for
      probes representing animate entities than for probes representing artifactual
      objects. Under CB, we found performance impairment relative to a "no-change"
      baseline condition. This inhibition effect induced by CB was modulated by the
      semantic congruency between the changed item and the probe in the case of probe
      images, but not for probe words. We discuss our results in the context of the
      literature on the negative priming effect.

PMID- 22964455
TI  - Endogenous sterol biosynthesis is important for mitochondrial function and cell
      morphology in procyclic forms of Trypanosoma brucei.
AB  - Sterol biosynthesis inhibitors are promising entities for the treatment of
      trypanosomal diseases. Insect forms of Trypanosoma brucei, the causative agent of
      sleeping sickness, synthesize ergosterol and other 24-alkylated sterols, yet also
      incorporate cholesterol from the medium. While sterol function has been
      investigated by pharmacological manipulation of sterol biosynthesis, molecular
      mechanisms by which endogenous sterols influence cellular processes remain
      largely unknown in trypanosomes. Here we analyse by RNA interference, the effects
      of a perturbation of three specific steps of endogenous sterol biosynthesis in
      order to dissect the role of specific intermediates in proliferation,
      mitochondrial function and cellular morphology in procyclic cells. A decrease in
      the levels of squalene synthase and squalene epoxidase resulted in a depletion of
      cellular sterol intermediates and end products, impaired cell growth and led to
      aberrant morphologies, DNA fragmentation and a profound modification of
      mitochondrial structure and function. In contrast, cells deficient in sterol
      methyl transferase, the enzyme involved in 24-alkylation, exhibited a normal
      growth phenotype in spite of a complete abolition of the synthesis and content of
      24-alkyl sterols. Thus, the data provided indicates that while the depletion of
      squalene and post-squalene endogenous sterol metabolites results in profound
      cellular defects, bulk 24-alkyl sterols are not strictly required to support
      growth in insect forms of T. brucei in vitro.

PMID- 22964456
TI  - On anisogamy and the evolution of 'sex roles'.

PMID- 22964457
TI  - Characterization of physalins and fingerprint analysis for the quality evaluation
      of Physalis alkekengi L. var. franchetii by ultra-performance liquid
      chromatography combined with diode array detection and electrospray ionization
      tandem mass spectrometry.
AB  - Physalins are important bioactive compounds from genus Physalis. They often occur
      as isomers, which makes the structural elucidation difficult. In the present
      study, the fragmentation behavior and UV characteristics of seven physalins from
      genus Physalis were firstly investigated using electrospray ionization tandem
      mass spectrometry (ESI-MS/MS) and diode array detection (DAD). Combined with
      ultra-performance liquid chromatography (UPLC) and DAD, the established approach
      to the structural identification of physalins by ESI-MS/MS was then applied to
      the analysis of Physalis alkekengi L. According to the UPLC retention behavior,
      the diagnostic UV spectra and the molecular structural information provided by
      MS/MS spectra, about 19 fingerprint peaks were identified, including 14 physalins
      and 5 other compounds. Finally, the established fingerprint method was applied to
      the analysis of 31 P. alkekengi L. samples collected from different locations,
      which reflected their similar chemical constituent properties. The proposed
      method provides a scientific and technical platform to the herbal industry for
      quality control and safety assurance of herbal preparations that contain this
      class of physalins.

PMID- 22964458
TI  - Let's retain control.

PMID- 22964459
TI  - Contribution of Rag1 to spatial memory ability in rats.
AB  - Rag1 plays a critical role in the development and maturation of lymphocytes, and
      is related to immune memory functions. Deletion of Rag1 results in a lack of
      mature functional B and T lymphocytes. Rag1 transcription is most apparent in
      regions of the postnatal brain with high neuronal cell density--the cerebellum
      and the hippocampal formation, both of which are relevant to learning and memory
      function. In this research, three pairs of shRNA targeting Rag1 and a pair of
      scrambled sequences were constructed, packaged within a lentiviral vector system,
      and transferred into the cultured rat hippocampal neuron cells in vitro.
      Meanwhile, the lentivirus was injected stereotaxically into CA3 of the rat
      hippocampus, where the positive immunofluorescence for GFP expression was
      located. Rag1 mRNA expression was detected by RT-PCR 7, 14 and 28 days after
      stereotaxic injection. Assessment in the Morris water maze test 28 days post
      stereotaxic injection showed a loss of spatial learning and memory in the
      experimental rats. In long-term potentiation research, the experimental group did
      not display remarkable disparity in comparison with the control group. These
      findings indicate that the knockdown of Rag1 expression in the hippocampus may
      impair spatial learning and memory ability in rats.

PMID- 22964460
TI  - Particle size: a missing factor in risk assessment of human exposure to toxic
      chemicals in settled indoor dust.
AB  - For researches on toxic chemicals in settled indoor dust, selection of dust
      fraction is a critical influencing factor to the accuracy of human exposure risk
      assessment results. However, analysis of the selection of dust fraction in recent
      studies revealed that there is no consensus. This study classified and presented
      researches on distribution of toxic chemicals according to dust particle size and
      on relationship between dust particle size and human exposure possibility.
      According to the literature, beyond the fact that there were no consistent
      conclusions on particle size distribution of adherent fraction, dust with
      particle size less than 100 MUm should be paid more attention and that larger
      than 250 MUm is neither adherent nor proper for human exposure risk assessment.
      Calculation results based on literature data show that with different selections
      of dust fractions, analytical results of toxic chemicals would vary up to 10
      fold, which means that selecting dust fractions arbitrarily will lead to large
      errors in risk assessment of human exposure to toxic chemicals in settled dust.
      Taking into account the influence of dust particle size on risk assessment of
      human exposure to toxic chemicals, a new methodology for risk assessment of human
      exposure to toxic chemicals in settled indoor dust is proposed and human exposure
      parameter systems to settled indoor dust are advised to be established at
      national and regional scales all over the world.

PMID- 22964461
TI  - Voltage-dependent conductance states of a single-molecule junction.
AB  - Ag-Sn-phthalocyanine-Ag  junctions are shown to exhibit three conductance states.
      While the junctions are conductive at low bias, their impedance drastically
      increases above a critical bias. Two-level fluctuations occur at intermediate
      bias. These characteristics may be used to protect a nanoscale circuit. Further
      experiments along with calculations reveal that the self-limiting conductance of
      the junctions is due to reversible changes of the junction geometry.

PMID- 22964462
TI  - DNA and oxidative damages decrease after ingestion of folic acid in patients with
      type 2 diabetes.
AB  - BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) is a chronic degenerative
      disease that promotes autoxidation of sugars, leading to the production of
      reactive oxygen species. This damage occurs especially at the level of cellular
      proteins, carbohydrates, lipids and DNA, thus playing an important role in the
      pathogenesis of late complications of T2DM. We investigated the effect of folic
      acid on DNA and oxidative damage in patients with T2DM. METHODS: We studied 30
      individuals diagnosed with T2DM and 30 control individuals without disease.
      Individuals with T2DM were prescribed 5 mg of folic acid, taken orally three
      times daily for 1 month. Samples were taken 15 and 30 days after treatment. DNA
      damage was determined using the micronucleus test in oral mucosa and oxidative
      stress by quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) as well as by
      quantifying total lipid peroxides. RESULTS: Individuals with T2DM had a higher
      number of micronuclei as well as higher levels of 8-OHdG and lipid peroxides than
      the control group (p = 0.001). Individuals with T2DM showed a significant
      reduction in the number of micronuclei and the concentration of 8-OHdG and lipid
      peroxides over time with folic acid intake. CONCLUSIONS: A positive correlation
      exists between oxidative stress produced by T2DM and DNA damage, so the use of an
      antioxidant such as folic acid in DM2 therapy is advisable for delaying
      complications due to T2DM-induced oxidative stress and DNA damage.

PMID- 22964463
TI  - Mineralization and toxicity reduction of textile dye neutral red in aqueous phase
      using BiOCl photocatalysis.
AB  - The BiOCl catalyst was prepared by hydrolysis method. The compound was
      extensively characterized by XRD, SEM, TEM, UV-vis measurements and BET surface
      area. The prepared material had average pore diameter about 6-13 nm. The BET
      surface area of the sample is about 40 m(2)/g. The photocatalytic degradation and
      toxicity reduction of textile dye neutral red (NR) was investigated in the
      presence of as prepared BiOCl. The analysis of (.)OH radical formation was
      performed by fluorescence technique. The intermediates and the final products of
      degradation were detected by high-performance liquid chromatography-photodiode
      array-electrospray ionization-mass spectrometry (HPLC-ESI-DAD-MS) technology.
      Decrease in chemical oxygen demand (COD) and dye absorbance of the photodegraded
      dye solution revealed a complete mineralization of NR into CO(2) and inorganic
      ions. The recycling experiments confirmed the relative stability of the catalyst.
      Finally, the luminescent marine bacteria Vibrio fischeri was used to assess the
      acute toxicity of samples prior to and after the photocatalytic treatment and it
      was found that toxicity was fully eliminated following photocatalytic
      degradation.

PMID- 22964464
TI  - Targeted inhibition of renal Rho kinase reduces macrophage infiltration and
      lymphangiogenesis in acute renal allograft rejection.
AB  - The Rho kinase pathway plays an important role in epithelial dedifferentiation
      and inflammatory cell infiltration. Recent studies suggest that inflammation
      promotes lymphangiogenesis, which has been associated with renal allograft
      rejection. We investigated whether targeted inhibition of the Rho kinase pathway
      in proximal tubular cells reduces inflammation and lymphangiogenesis in acute
      renal allograft rejection. The Rho kinase inhibitor Y27632 was coupled to
      lysozyme (Y27632-lysozyme), providing a kidney-specific conjugate that can
      release its drug in proximal tubular cells. Isogenic (Fisher-Fisher, n=18), or
      allogenic (Fisher-Lewis, n=24) kidney transplantations were performed, with the
      contralateral kidney remaining in situ. To elicit acute rejection, no
      immunosuppressive treatment was given. Animals were treated daily with Y27632
      lysozyme (10 mg/kg/day i.v.) or vehicle (saline i.v.) until sacrifice (1 or 4
      days post-transplantation). After allogenic transplantation, interstitial
      macrophage accumulation was strongly reduced by Y27632-lysozyme at day 4 after
      transplantation. Interstitial lymphangiogenesis, which was induced in allografts
      as compared to control kidney, was also reduced by renal Rho kinase inhibition at
      day 4 after transplantation. The increase of vimentin and procollagen-1alpha1
      gene expression in renal allografts from day 1 to day 4 after transplantation was
      significantly reduced by Y27632-lysozyme. Y27632-lysozyme did not affect systolic
      blood pressure in isogenic or allogenic transplantation groups. In cultured
      tubular epithelial cells (NRK-52E), Rho kinase inhibition dose-dependently
      reduced IL-1beta-induced MCP-1 gene expression. Renal inhibition of Rho kinase
      causes a marked reduction in renal inflammation and renal lymphangiogenesis
      during acute transplant rejection, suggesting that this treatment regimen is a
      valuable future treatment in renal transplantation.

PMID- 22964465
TI  - Involvement of presynaptic voltage-dependent Kv3 channel in endothelin-1-induced
      inhibition of noradrenaline release from rat gastric sympathetic nerves.
AB  - We previously reported that two types of K(+) channels, the BK type Ca(2+)
      activated K(+) channel coupled with phospholipase C (PLC) and the voltage
      dependent K(+) channel (Kv channel), are, respectively, involved in the
      prostanoid TP receptor- and muscarinic M(2) receptor-mediated inhibition of
      noradrenaline (NA) release from rat gastric sympathetic nerves. In the present
      study, therefore, we examined whether these K(+) channels are involved in
      endothelin-1-induced inhibition of NA release, using an isolated, vascularly
      perfused rat stomach. The gastric sympathetic postganglionic nerves around the
      left gastric artery were electrically stimulated twice at 2.5 Hz for 1 min, and
      endothelin-1 was added during the second stimulation. Endothelin-1 (1, 2 and 10
      nM) dose-dependently inhibited gastric NA release. Endothelin-1 (2 nM)-induced
      inhibition of NA release was neither attenuated by PLC inhibitors [U-73122 (3
      MUM) and ET-18-OCH(3) (3 MUM)] nor by Ca(2+)-activated K(+) channel blockers
      [charybdotoxin (0.1 MUM) (a blocker of BK type K(+) channel) and apamin (0.3 MUM)
      (a blocker of SK type K(+) channel)]. The endothelin-1-induced inhibitory
      response was also not attenuated by alpha-dendrotoxin (0.1 MUM) (a selective
      inhibitor of Kv1 channel), but abolished by 4-aminopyridine (20 MUM) (a
      selectively inhibitory dose for Kv3 channel). These results suggest the
      involvement of a voltage-dependent Kv3 channel in the endothelin-1-induced
      inhibition of NA release from the gastric sympathetic nerves in rats.

PMID- 22964466
TI  - Inhibitory effect of selaginellin on high glucose-induced apoptosis in
      differentiated PC12 cells: role of NADPH oxidase and LOX-1.
AB  - Hyperglycemia clearly plays a key role in the development and progression of
      diabetic neuropathy. Hyperglycemia induces oxidative stress to generate reactive
      oxygen species in diabetic neurons resulting in neuronal damage and dysfunction.
      Apoptosis has been proposed as a possible mechanism for high glucose-induced
      neural dysfunction and neuronal cell injury. High glucose per se enhances lectin
      like oxidized low density lipoprotein receptor-1 (LOX-1) expression via
      activation of NADPH oxidase/reactive oxygen species pathway in endothelial cells.
      Selaginellin, a component extracted from Saussurea pulvinata (Hook. et Grev.)
      Maxim, was assessed for its ability to protect rat pheochromocytoma (PC12) cells
      against oxidative toxicity induced by high glucose. The differentiated PC12 cells
      were pretreated with various concentrations (10(-7), 3*10(-7) or 10(-6) M) of
      selaginellin for 1 h and then co-treated with selaginellin and D-glucose (75 mM)
      for 72 h. Selaginellin was shown to protect differentiated PC12 cells against
      high glucose toxicity, as determined by characteristic morphological features,
      cell viability, and apoptosis as evaluated by Hoechst 33,258 staining assay,
      annexin V-propidium iodide double staining assay and caspase-3 activity. In
      addition, the increase in NADPH oxidase activity, mRNA expression of NADPH
      oxidase subunits (NOX-1 and NOX-2) and LOX-1, and reactive oxygen species
      production induced by high glucose were significantly inhibited by selaginellin
      or by anti-LOX-1 antibody. The present study demonstrated that inhibitory effect
      of selaginellin on high glucose-induced cell injury and apoptosis in
      differentiated PC12 cells is related to inhibition of LOX-1/NADPH oxidase
      reactive oxygen species/caspase-3 signaling pathway.

PMID- 22964467
TI  - Prostaglandin E2 receptor subtypes in human blood and vascular cells.
AB  - Prostaglandin E(2) is produced in inflammatory responses via the cyclooxygenase
      pathway and regulates a variety of physiological and pathological reactions
      through four different receptor subtypes; EP(1), EP(2), EP(3) and EP(4). The role
      of the classical prostanoid receptors stimulated by prostaglandin I(2) and
      thromboxane A(2) in the blood circulation has been largely studied, whereas the
      other receptors such as EP activated by prostaglandin E(2), have been recently
      shown to be also implicated. There is now increasing evidence suggesting an
      important role of EP(3) and EP(4) receptor subtypes in the control of the human
      vascular tone and remodeling of the vascular wall as well in platelet aggregation
      and thrombosis. These receptors are implicated in vascular homeostasis and in the
      development of some pathological situations, such as atherosclerosis, aneurysms
      and hypertension. The use of specific EP agonists/antagonists would provide a
      novel cardiovascular therapeutic approach. In this review, we discuss the role of
      prostaglandin E(2) receptors in the control of human blood and vascular cells.

PMID- 22964468
TI  - Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea
      compound NS5806.
AB  - We examined the effects of the sulfonylurea compound NS5806 on neuronal A-type
      channel function. Using whole-cell patch-clamp we studied the effects of NS5806
      on the somatodendritic A-type current (I(SA)) in cultured hippocampal neurons and
      the currents mediated by Kv4.2 channels coexpressed with different auxiliary beta
      subunits, including both Kv channel interacting proteins (KChIPs) and dipeptidyl
      aminopeptidase-related proteins (DPPs), in HEK 293 cells. The amplitude of the
      I(SA) component in hippocampal neurons was reduced in the presence of 20 MUM
      NS5806. I(SA) decay kinetics were slowed and the recovery kinetics accelerated,
      but the voltage dependence of steady-state inactivation was shifted to more
      negative potentials by NS5806. The peak amplitudes of currents mediated by
      ternary Kv4.2 channel complexes, associated with DPP6-S (short splice-variant)
      and either KChIP2, KChIP3 or KChIP4, were potentiated and their macroscopic
      inactivation slowed by NS5806, whereas the currents mediated by binary Kv4.2
      channels, associated only with DPP6-S, were suppressed, and the NS5806-mediated
      slowing of macroscopic inactivation was less pronounced. Neither potentiation nor
      suppression and no effect on current decay kinetics in the presence of NS5806
      were observed for Kv4.2 channels associated with KChIP3 and the N-type
      inactivation-conferring DPP6a splice-variant. For all recombinant channel
      complexes, NS5806 slowed the recovery from inactivation and shifted the voltage
      dependence of steady-state inactivation to more negative potentials. Our results
      demonstrate the activity of NS5806 on native I(SA) and possible molecular
      correlates in the form of recombinant Kv4.2 channels complexed with different
      KChIPs and DPPs, and they shed some light on the mechanism of NS5806 action.

PMID- 22964469
TI  - Inhibitory effects of Drynaria fortunei extract on house dust mite antigen
      induced atopic dermatitis in NC/Nga mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Drynaria fortunei (Kunze) J. Sm has been widely
      used in traditional medicine for the treatment of inflammation, hyperlipidemia,
      arteriosclerosis, rheumatism, and bone healing. We investigated the anti
      inflammatory effects of a 70% ethanol extract of Drynaria fortunei (DFE).
      MATERIALS AND METHODS: We evaluated the anti-inflammatory effects of topically
      applied DFE on house dust mite Dermatophargoides farinae-induced atopic
      dermatitis-like skin lesions in NC/Nga mice. RESULTS: Treatment of NC/Nga mice
      with DFE reduced the dermatitis score, ear thickness, and serum levels of IgE,
      IgG1, and IL-6. Histopathological analyses of ear and skin lesions showed
      inhibition of the thickening of the epidermis and reduced epidermal/dermal
      infiltration of inflammatory cells. In ear lesions, mRNA expression levels of IL
      4, IL-6, and tumor necrosis factor-alpha were reduced by DFE treatment.
      CONCLUSIONS: DFE inhibited the development of dermatitis-like skin lesions in
      NC/Nga mice. These results suggest that DFE may be a therapeutic candidate for
      the treatment of AD.

PMID- 22964470
TI  - Development of a refined tenocyte differentiation culture technique for tendon
      tissue engineering.
AB  - We have established that human tenocytes can differentiate in the absence of
      exogenous fetal bovine serum (FBS) but in the presence of insulin-like growth
      factor-1 (IGF-1) and transforming growth factor-beta3 (TGF-beta3). The extent of
      tenocyte differentiation was assessed by examining cell survival, collagen
      synthesis, cell morphology and expression of tenocyte differentiation markers
      such as scleraxis (Scx), tenomodulin (Tnmd), collagen type I (Col-I) and decorin
      (Dcn). Our results indicate that 50 ng/ml IGF-1 and 10 ng/ml TGF-beta3 (in the
      absence of FBS) were capable of maintaining in vitro human tenocyte survival in
      14-day cultures. The extent of collagen synthesis and messenger ribonucleic acid
      expression of Scx, Tnmd, Col-I and Dcn were significantly upregulated in response
      to IGF-1 and TGF-beta3. These findings have shown for the first time that human
      tenocytes can be maintained in long-term culture, in serum-free conditions,
      making this approach a suitable one for the purpose of tendon tissue engineering.

PMID- 22964471
TI  - Sharps injuries and exposure to blood and bloodstained body fluids involving
      medical waste handlers.
AB  - Exposure to healthcare waste can result in disease or injury. Though much
      attention is paid to the safety of healthcare professionals and their protection
      from sharps injury and exposure to blood and bloodstained body fluids (BBFs), the
      welfare and safety of non-healthcare professionals who are collecting,
      transporting and disposing waste has received very little attention. The
      objective of this study was to understand the incidence of sharps injury and
      occupational BBF exposure of mucous membranes involving medical waste handlers
      (MWHs). A cross-sectional study was carried out using a self-administered
      questionnaire, observation and interview. Data analysis was performed using SPSS
      version 16. The chi(2) value was calculated and P <0.05 was considered
      statistically significant. One or more incidents of sharps injuries and BBF
      exposures to mucous membranes occurred among 42.1% and 67.5% of MWHs
      respectively. None of the respondents was immunized with hepatitis B vaccine
      owing to the high cost of immunization and absence of free universal availability
      of the vaccine for the adult population. Less than 50% of MWHs wore either gloves
      or boots while performing their activities. Even though all knew about HIV, most
      of the respondents demonstrated a lack of knowledge regarding viral hepatitis.
      The risk of sharps injury and BBF exposure appeared high in MWHs. The
      establishment of safe waste-management techniques and the appropriate use of
      personnel protective equipment among MWHs in Addis Ababa is urgently required.

PMID- 22964472
TI  - Development of an international interdisciplinary course: a strategy to promote
      cultural competence and collaboration.
AB  - Now, more than ever, nurses are practicing in settings in which cultural
      competence and teamwork are essential to providing quality care. The expectation
      that nurses provide effective care across varied population groups highlights the
      need for attainment of cultural competency by baccalaureate nursing graduates.
      Nursing programs must develop strategies to address this educational need. In
      this article, the authors share their experiences in the development of an
      international interdisciplinary course that combined academic service learning
      with cultural immersion to promote the development of cultural competence and
      collaboration among students. By developing an interdisciplinary course that is
      of interest to a wide range of students, faculty can be successful in providing
      an opportunity for students with varied career paths to be better prepared to
      live and work in the world's global community.

PMID- 22964473
TI  - Do topical antibiotics help prevent infection in minor traumatic uncomplicated
      soft tissue wounds?

PMID- 22964474
TI  - Molecular characterization of Xp chromosome deletion in a fertile cow.
AB  - A young cow of the Marchigiana breed (central Italy) with normal body
      conformation and external genitalia underwent routine cytogenetic analyses prior
      to its use for reproduction. After normal chromosome staining, only one X
      chromosome was observed with a normal diploid number (2n = 60) in all 200 studied
      cells. Subsequent cytogenetic analyses by using both CBA- and RBA-banding
      techniques evidenced that almost all the p arms of the other X chromosome was
      lacking. Detailed FISH-mapping analyses with BAC covering this Xp arm region
      demonstrated that this large chromosome region was deleted. RBA-banding showed
      that the deleted X was late replicating. CGH array analysis evidenced that
      deletion involves the Xp arm from the telomere to around 39.5 Mb, referring to
      the BosTau6 cattle genome assembly. This abnormality deletes about 40 Mb of the X
      chromosome sequence, but, despite the large number of genes deleted, none of them
      are programmed to escape from inactivation. This can explain the normal phenotype
      of the female which is actually pregnant. Finally, we evidenced, by analysis of
      an SNP mapped to the deleted region (SNP rs29024121), that the only normal (e.g.
      nondeleted) X chromosome present derives from the father. Hence, the deletion has
      a maternal origin.

PMID- 22964475
TI  - A randomized clinical trial of the effects of supplemental calcium and vitamin D3
      on the APC/beta-catenin pathway in the normal mucosa of colorectal adenoma
      patients.
AB  - APC/beta-catenin pathway perturbation is a common early event in colorectal
      carcinogenesis and is affected by calcium and vitamin D in basic science studies.
      To assess the effects of calcium and vitamin D on adenomatous polyposis coli
      (APC), beta-catenin, and E-cadherin expression in the normal appearing colorectal
      mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double
      blinded, placebo-controlled 2 * 2 factorial clinical trial. Pathology-confirmed
      colorectal adenoma cases were treated with 2 g/day elemental calcium and/or 800
      IU/day vitamin D(3) versus placebo over 6 months (N = 92; 23/group). Overall APC,
      beta-catenin, and E-cadherin expression and distributions in colon crypts in
      normal-appearing rectal mucosa biopsies were detected by standardized automated
      immunohistochemistry and quantified by image analysis. In the vitamin D(3)
      supplemented group relative to placebo, the proportion of APC in the upper 40% of
      crypts (Phih APC) increased 21% (P = 0.01), beta-catenin decreased 12% (P =
      0.18), E-cadherin increased 72% (P = 0.03), and the Phih APC/beta-catenin ratio
      (APC/beta-catenin score) increased 31% (P = 0.02). In the calcium-supplemented
      group Phih APC increased 10% (P = 0.12), beta-catenin decreased 15% (P = 0.08),
      and the APC/beta-catenin score increased 41% (P = 0.01). In the calcium/vitamin
      D(3)-supplemented group, beta-catenin decreased 11% (P = 0.20), E-cadherin
      increased 51% (P = 0.08), and the APC/beta-catenin score increased 16% (P =
      0.26). These results support (i) that calcium and vitamin D modify APC, beta
      catenin, and E-cadherin expression in humans in directions hypothesized to reduce
      risk for colorectal neoplasms, (ii) calcium and vitamin D as potential
      chemopreventive agents against colorectal neoplasms, and (iii) the potential of
      APC, beta-catenin, and E-cadherin expression as modifiable, preneoplastic risk
      biomarkers for colorectal neoplasms.

PMID- 22964477
TI  - Protective actions of globular and full-length adiponectin on human endothelial
      cells: novel insights into adiponectin-induced angiogenesis.
AB  - BACKGROUND/AIMS: Adiponectin levels are decreased in diabetes and
      atherosclerosis. Coexisting hyperglycaemia and systemic inflammation predisposes
      to dysregulated angiogenesis and vascular disease. We investigated the effect of
      globular adiponectin (gAd) and full-length adiponectin (fAd) on angiogenesis and
      pro-angiogenic molecules, i.e. matrix metalloproteinase (MMP)-2, MMP-9 and
      vascular endothelial growth factor (VEGF), in human microvascular endothelial
      cells (HMEC-1). METHODS: Angiogenesis was assessed by studying capillary tube
      formation in HMEC-1 on growth factor-reduced Matrigel. Endothelial cell migration
      assay was performed in a modified Boyden chamber. RESULTS: Endothelial cell
      proliferation, in vitro migration and angiogenesis were significantly increased
      by gAd (mediated by AdipoR1, AMPK-Akt pathways), and gAd significantly increased
      MMP-2, MMP-9 and VEGF expression levels. The effect of gAd on VEGF appears to be
      mediated by AdipoR1, whilst the effect of gAd on MMP-2 and MMP-9 appears to be
      mediated by AdipoR1 and AdipoR2. Only endothelial cell proliferation was
      significantly increased by fAd in human microvascular endothelial cells and
      appears to be mediated by AdipoR2. No significant effects on MMP-2, MMP-9 and
      VEGF were observed. Importantly, gAd decreased glucose and C-reactive protein
      induced angiogenesis with a concomitant reduction in MMP-2, MMP-9 and VEGF in
      HMEC-1 cells. CONCLUSION: We report novel insights into the mechanisms of
      adiponectin on angiogenesis.

PMID- 22964476
TI  - Dietary administration of delta- and gamma-tocopherol inhibits tumorigenesis in
      the animal model of estrogen receptor-positive, but not HER-2 breast cancer.
AB  - Tocopherol, a member of the vitamin E family, consists of four forms designated
      as alpha, beta, gamma, and delta. Several large cancer prevention studies with
      alpha-tocopherol have reported no beneficial results, but recent laboratory
      studies have suggested that delta- and gamma-tocopherol may be more effective. In
      two different animal models of breast cancer, the chemopreventive activities of
      individual tocopherols were assessed using diets containing 0.3% of tocopherol
      (alpha-, delta-, or gamma-) or 0.3% of a gamma-tocopherol rich mixture (gamma
      TmT). Although administration of tocopherols did not prevent human epidermal
      growth factor receptor 2 (HER2/neu)-driven tumorigenesis, delta- and gamma
      tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N
      nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an
      average tumor burden of 10.6 +/- 0.8 g in the control group at 11 weeks, whereas
      dietary administration of delta- and gamma-tocopherols significantly decreased
      tumor burden to 7.2 +/- 0.8 g (P < 0.01) and 7.1 +/- 0.7 g (P < 0.01),
      respectively. Tumor multiplicity was also reduced in delta- and gamma-tocopherol
      treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In
      contrast, alpha-tocopherol did not decrease tumor burden or multiplicity. In
      mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase
      9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers
      (Bcl-2, XIAP) were inhibited by delta-tocopherol, gamma-tocopherol, and gamma
      TmT. Furthermore, markers of cell proliferation (PCNA, PKCalpha), survival (PPAR
      gamma, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by delta- and
      gamma-tocopherols. Both delta- and gamma-tocopherols, but not alpha-tocopherol,
      seem to be promising agents for the prevention of hormone-dependent breast
      cancer.

PMID- 22964478
TI  - Osteoprotegerin predicts long-term outcome in patients with ST-segment elevation
      myocardial infarction treated with primary percutaneous coronary intervention.
AB  - BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in
      immune, skeletal and vascular systems. Data suggest that high circulating OPG
      levels are associated with an increased risk of cardiovascular disease. We
      analyzed the association between OPG and long-term outcome in patients with ST
      segment elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (pPCI). METHODS: We included 716 consecutive STEMI patients
      admitted to a single high-volume invasive heart center from September 2006 to
      December 2008. Endpoints were all-cause mortality, repeat myocardial infarction,
      admission due to heart failure and combinations thereof. Median follow-up lasted
      27 months (interquartile range: 22-33). RESULTS: OPG levels exhibited a non
      Gaussian distribution and were therefore divided into quartiles. High levels of
      OPG were significantly associated with a worse outcome. After adjustment for
      conventional risk factors (e.g. C-reactive protein, estimated glomerular
      filtration rate, symptom-to-balloon time and troponin I) using Cox regression,
      OPG remained a significantly independent predictor of death (HR per increase in
      OPG quartile: 1.28; CI: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR:
      1.30; CI: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI:
      1.18-1.90; p = 0.001). CONCLUSION: This study shows that OPG independently
      predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this
      knowledge could improve risk stratification and overall outcome.

PMID- 22964479
TI  - Anti-beta(2)GPI/beta(2)GPI induced TF and TNF-alpha expression in monocytes
      involving both TLR4/MyD88 and TLR4/TRIF signaling pathways.
AB  - Our previous study demonstrated that Toll-like receptor 4 (TLR4) could act as a
      co-receptor with annexin A2 (ANX2) mediating anti-beta2-glycoprotein I/beta2
      glycoprotein I (anti-beta(2)GPI/beta(2)GPI)-induced tissue factor (TF) expression
      in human acute monocytic leukemia cell line THP-1. In the current study, we
      further explored the roles of TLR4 and its adaptors, MyD88 and TRIF, in anti
      beta(2)GPI/beta(2)GPI-induced the activation of human blood monocytes and THP-1
      cells and the relationship among TLR4, beta(2)GPI and ANX2 in this process. The
      results showed that treatment of monocytes or THP-1 cells with anti
      beta(2)GPI/beta(2)GPI complex could increase TF, MyD88, TRIF as well as TNF-alpha
      (tumor necrosis factor alpha) expression. These effects were blocked by addition
      of TAK-242, a blocker of signaling transduction mediated by the intracellular
      domain of TLR4. Moreover, TLR4/beta(2)GPI/ANX2 complex could be detected in THP-1
      cell lysates. Overall, our results indicate that anti-beta(2)GPI/beta(2)GPI
      complex induced TF and TNF-alpha expression involving both TLR4/MyD88 and
      TLR4/TRIF signaling pathways and TLR4 and its adaptors might be molecular targets
      for therapy of antiphospholipid syndrome (APS).

PMID- 22964480
TI  - Regulation of NKG2D-ligand cell surface expression by intracellular calcium after
      HDAC-inhibitor treatment.
AB  - In this study we demonstrate that histone deacetylase (HDAC)-inhibitor mediated
      cell surface expression of the structural different NKG2D-ligands MICA/B and
      ULBP2 is calcium-dependent. Treatment with the calcium chelator EGTA inhibited
      constitutive as well as HDAC-inhibitor induced MICA/B and ULBP2 cell surface
      expression on melanoma cells and Jurkat T-cells. A NKG2D-dependent cytolytic
      assay and staining with a recombinant NKG2D-Fc fusion protein showed that calcium
      chelation impaired the functional ability of NKG2D-ligands induced by HDAC
      inhibitor treatment. The HDAC-inhibitor induced cell surface expression of ULBP2,
      but not MICA/B, was sensitive to treatment calmidazolium and trifluoperazine, two
      agents known to block calcium signaling. siRNA-mediated knock-down of the calcium
      regulated proteins calmodulin or calpain did however not affect NKG2D-ligand cell
      surface expression on Jurkat T-cells. We further show that secretion and cell
      surface binding of the calcium-regulating protein galectin-1 is enhanced upon
      HDAC-inhibitor treatment of melanoma cells. However, binding of galectin-1 to
      cell surface glycoproteins was not critical for constitutive or HDAC-inhibitor
      induced MICA/B and ULBP2 cell surface expression. We provide evidence that MICA/B
      and ULBP2 cell surface expression is controlled differently by calcium, which
      adds to the increasing perception that cell surface expression of MICA/B and
      ULBP2 is controlled by distinct signal transduction pathways.

PMID- 22964481
TI  - Altered microRNA expression levels in mononuclear cells of patients with
      pulmonary and pleural tuberculosis and their relation with components of the
      immune response.
AB  - Different lines of evidence demonstrate that microRNAs (miRNAs) play an important
      role in host-pathogen interactions. In this study we investigated the expression
      patterns of several miRNAs, most of them involved in regulating inflammatory
      responses, in patients with tuberculosis (TB). In order to understand the events
      occurring at the site of infection, we employed mononuclear cells obtained from
      both peripheral blood (PBMC) and pleural fluids (PFMC) of patients.
      Interestingly, we found that the miRNA signature of each compartment is
      different, with a strong down-regulation in PFMCs of miR-223, miR-144* and miR
      421. In addition, we observed that miR-146a expression is also down-regulated in
      tuberculosis patients, both in PBMCs and PFMCs while miR-424 levels are elevated
      only in the peripheral compartments. We also showed that systemic expression of
      these miRNAs changes upon specific treatment and is associated with IL-6 levels,
      a cytokine playing a substantial role in TB immunopathology. Present results
      contribute to a better knowledge of the host responses in TB pathogenesis,
      pointing out the role of miRNAs in this disease.

PMID- 22964482
TI  - Fc receptor-gamma subunits with both polar or non-polar amino acids at position
      of T22 are capable of restoring surface expression of the high-affinity IgE
      receptor and degranulation in gamma subunit-deficient rat basophilic leukemia
      cells.
AB  - The high-affinity IgE receptor (FcERI) is formed by the IgE-binding alpha
      subunit, beta subunit and gamma subunits homodimer. All three subunits are
      required for proper expression of the receptor on the plasma membrane of mast
      cells and basophils. However, the exact molecular mechanism of inter-subunit
      interactions required for correct expression and function of the FcERI complex
      remains to be identified. A recent study suggested that polar aspartate at
      position 194 within the transmembrane domain of the alpha subunit could interact
      by hydrogen bonding with polar threonine at position 22 in the transmembrane
      domains of the gamma subunits. To verify this, we used previously isolated rat
      basophilic leukemia (RBL)-2H3 variant cells deficient in the expression of the
      FcERI-gamma subunit (FcR-gamma), and transfected them with DNA vectors coding for
      FcR-gamma of the wild-type or mutants in which T22 was substituted for nonpolar
      alanine (T22A mutant) or polar serine (T22S mutant). Analysis of the
      transfectants showed that both T22A and T22S mutants were capable to restore
      surface expression of the FcERI similar to wild-type FcR-gamma. Furthermore,
      cells transfected with wild-type, T22A or T22S FcR-gamma showed comparably
      enhanced FcERI-mediated degranulation. Our data indicate that substitution of FcR
      gamma T22 with non-polar amino acid does not interfere with surface expression of
      the FcERI and its signaling capacity.

PMID- 22964483
TI  - Effects of coagulation on the autofluorescence pattern of ARPE-19 cells: an in
      vitro study.
AB  - OBJECTIVE: Changes in fundus autofluorescence (AF) are observed in various
      retinal disorders. Lipofuscin accumulation within the retinal pigment epithelium
      (RPE) is a source of fundus AF (FAF); however, the causes of short-term increases
      in FAF observed in inflammatory conditions or after laser treatment are unknown.
      Here, we describe an RPE cell culture model that is useful for investigations of
      FAF. METHODS: ARPE-19 cells were cultured in 2-well chamber slides. Cells were
      exposed to isolated rabbit photoreceptor outer segments (POS) to mimic in vivo
      phagocytic activity. The AF of RPE cells exposed to POS was measured before and
      after focal coagulation of the cultures. AF was measured over a period of 4
      weeks. Cell lysates were examined by two-dimensional (2D) gel electrophoresis and
      mass spectrometry analysis. RESULTS: The exposure of ARPE cells to POS did not
      lead to increased AF; however, after coagulation, cells exposed to POS showed a
      statistically significant increase in AF (p < 0.05). 2D electrophoresis of the
      cell lysates revealed changes in 3 proteins. One of these proteins, identified by
      mass spectrometry as ezrin-radixin-moesin-binding phosphoprotein 50, was reduced
      in the coagulated cell population. CONCLUSIONS: We have established an in vitro
      model of RPE cells in culture that can be used to evaluate the development of AF
      and changes in cellular proteins that accompany laser photocoagulation.

PMID- 22964484
TI  - Inhibition of monocarboxylate transporter 2 induces senescence-associated
      mitochondrial dysfunction and suppresses progression of colorectal malignancies
      in vivo.
AB  - Senescence, an inherent tumor suppressive mechanism, is a critical determinant
      for chemotherapy. In the present study, we show that the monocarboxylate
      transporter 2 (MCT2) protein was tumor-selectively expressed in human colorectal
      malignancies and knockdown of MCT2 induces mitochondrial dysfunction, cell-cycle
      arrest, and senescence without additional cellular stress in colorectal cancer
      cell lines. Moreover, the reactive oxygen species (ROS) scavenger, N
      acetylcysteine, blocked MCT2 knockdown-induced growth arrest and cellular
      senescence, indicating a pivotal role of ROS in this pathway. Dramatic induction
      of mitochondrial superoxide generation and decrease in ATP production was
      observed, indicating that mitochondrial dysfunction is the major mechanism
      underlying MCT2 knockdown-induced ROS generation. Senescence-associated DNA
      damage was also evident from the increase in promyelocytic leukemia bodies,
      gammaH2AX foci, and SAHF. Conversely, overexpression of MCT2 prevented
      doxorubicin-induced ROS accumulation (P = 0.0002) and cell growth inhibition (P =
      0.001). MCT2 knockdown suppressed KRAS mutant colorectal tumor growth in vivo. In
      addition, MCT2 knockdown and cytostatic drug combination further enhanced the
      antitumor effect. These findings support the use of MCT2 as a promising target
      for inhibition of colorectal cancer.

PMID- 22964485
TI  - Sangivamycin-like molecule 6 exhibits potent anti-multiple myeloma activity
      through inhibition of cyclin-dependent kinase-9.
AB  - Despite significant treatment advances over the past decade, multiple myeloma
      (MM) remains largely incurable. In this study we found that MM cells were
      remarkably sensitive to the death-inducing effects of a new class of sangivamycin
      like molecules (SLM). A panel of structurally related SLMs selectively induced
      apoptosis in MM cells but not other tumor or nonmalignant cell lines at
      submicromolar concentrations. SLM6 was the most active compound in vivo, where it
      was well tolerated and significantly inhibited growth and induced apoptosis of MM
      tumors. We determined that the anti-MM activity of SLM6 was mediated by direct
      inhibition of cyclin-dependent kinase 9 (CDK9), which resulted in transcriptional
      repression of oncogenes that are known to drive MM progression (MAF, CCND1, MYC,
      and others). Furthermore, SLM6 showed superior in vivo anti-MM activity more than
      the CDK inhibitor flavopiridol, which is currently in clinical trials for MM.
      These findings show that SLM6 is a novel CDK9 inhibitor with promising
      preclinical activity as an anti-MM agent.

PMID- 22964486
TI  - Brain-resident microglia predominate over infiltrating myeloid cells in
      activation, phagocytosis and interaction with T-lymphocytes in the MPTP mouse
      model of Parkinson disease.
AB  - Parkinson disease (PD) is characterized by dopaminergic neurodegeneration in the
      substantia nigra (SN). Recent evidence suggests that innate and adaptive immune
      responses can influence dopaminergic cell death in animal models of PD. However,
      the precise role of mononuclear phagocytes, key players in damaged tissue
      clearance and cross-talk with cells of adaptive immune system, remains open in
      PD. Mononuclear phagocytes in the brain occur as brain-resident microglia and as
      brain-infiltrating myeloid cells. To elucidate their differential contribution in
      the uptake of dopaminergic cell debris and antigen presentation capacity, we
      labeled nigral dopaminergic neurons retrogradely with inert rhodamine-conjugated
      latex retrobeads before inducing their degeneration by subchronic 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. We used green
      fluorescent protein (GFP)-expressing bone marrow chimeric mice to differentiate
      brain-infiltrating from brain-resident myeloid cells. We found that half of both
      endogenous (GFP-) and exogenous (GFP+) microglia (Iba1+) in the SN incorporated
      the tracer from degenerating dopaminergic neurons 1d after MPTP intoxication. In
      absolute numbers, endogenous microglia were much more activated to macrophages
      compared to exogenous myeloid cells at 1d after MPTP. Mainly the endogenous,
      tracer-phagocytosing microglia expressed the major histocompatibility complex
      (MHC) class II molecule for antigen presentation. Additionally, T-lymphocytes
      (Iba1-/GFP+/CD3+), which infiltrate the MPTP-lesioned SN, were mainly in direct
      contact with MHCII+ endogenous microglia. Our data suggest that brain-resident
      microglia are predominantly implicated in the removal of dopaminergic cell debris
      and the cross-talk with infiltrating T-lymphocytes in the SN in the MPTP mouse
      model of PD.

PMID- 22964487
TI  - Posterior dislocation of both ends of the clavicle treated with allograft tendon
      reconstruction: a case report.

PMID- 22964489
TI  - SIRT3 regulation of mitochondrial oxidative stress.
AB  - Mitochondria play a central role in the production of reactive oxygen species as
      byproducts of metabolism and energy production. In order to protect cellular
      structures from oxidative stress-induced damage, cells have evolved elegant
      mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin,
      SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of
      substrates involved in both ROS production and detoxification. This review will
      summarize recent findings on the regulation of mitochondrial ROS homeostasis by
      SIRT3.

PMID- 22964488
TI  - Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular
      therapy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most highly lethal malignancies
      ranking as the third leading-cause of cancer-related death worldwide. Although
      surgical resection and transplantation are effective curative therapies, very few
      patients qualify for such treatments due to the advanced stage of the disease at
      diagnosis. In this context, loco-regional therapies provide a viable therapeutic
      alternative with minimal systemic toxicity. However, as chemoresistance and tumor
      recurrence negatively impact the success of therapy resulting in poorer patient
      outcomes it is imperative to identify new molecular target(s) in cancer cells
      that could be effectively targeted by novel agents. Recent research has
      demonstrated that proliferation in HCC is associated with increased glucose
      metabolism. The glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), a multifunctional protein primarily recognized for its role in glucose
      metabolism, has already been shown to affect the proliferative potential of
      cancer cells. In human HCC, the increased expression of GAPDH is invariably
      associated with enhanced glycolytic capacity facilitating tumor progression.
      Though it is not yet known whether GAPDH up-regulation contributes to
      tumorigenesis sensu stricto, emerging evidence points to the existence of a link
      between GAPDH up-regulation and the promotion of survival mechanisms in cancer
      cells as well as chemoresistance. The involvement of GAPDH in several
      hepatocarcinogenic mechanisms (e.g. viral hepatitis, metabolic alterations) and
      its sensitivity to a new class of prospective anticancer agents prompted us to
      review the current understanding of the therapeutic potential of targeting GAPDH
      in HCC.

PMID- 22964490
TI  - Functional anatomy of timing differs for production versus prediction of time
      intervals.
AB  - Timing is required both for estimating the duration of a currently unfolding
      event, or predicting when a future event is likely to occur. Yet previous studies
      have shown these processes to be neuroanatomically distinct with duration
      estimation generally activating a distributed, predominantly right-sided, fronto
      striatal network and temporal prediction activating left-lateralised inferior
      parietal cortex. So far, these processes have been examined independently and
      using widely differing paradigms. We used fMRI to identify and compare the neural
      correlates of duration estimation, indexed by temporal reproduction, to those of
      temporal prediction, indexed by temporal orienting, within the same experimental
      paradigm. Behavioural data confirmed that accurate representations of the cued
      interval were evident for both temporal reproduction and temporal orienting
      tasks. Direct comparison of temporal tasks revealed activation of a right
      lateralised fronto-striatal network when timing was measured explicitly by a
      temporal reproduction task but left inferior parietal cortex, left premotor
      cortex and cerebellum when timing was measured implicitly by a temporal orienting
      task. Therefore, although both production and prediction of temporal intervals
      required the same representation of time for their successful execution, their
      distinct neural signatures likely reflect the different ways in which this
      temporal representation was ultimately used: either to produce an overt estimate
      of an internally generated time interval (temporal reproduction) or to enable
      efficient responding by predicting the offset of an externally specified time
      interval (temporal orienting). This cortical lateralization may reflect right
      hemispheric specificity for overtly timing a currently elapsing duration and left
      hemispheric specificity for predicting future stimulus onset in order to optimize
      information processing.

PMID- 22964491
TI  - Molecules with multiple switching units on a Au(111) surface: self-organization
      and single-molecule manipulation.
AB  - Three different molecules, each containing two azobenzene switching units, were
      synthesized, successfully deposited onto a Au(111) surface by sublimation and
      studied by scanning tunneling microscopy at low temperatures. To investigate the
      influence of electronic coupling between the switching units as well as to the
      surface, the two azo moieties were connected either via pi-conjugated para
      phenylene or decoupling meta-phenylene bridges, and the number of tert-butyl
      groups was varied in the meta-phenylene-linked derivatives. Single molecules were
      found to be intact after deposition as identified by their characteristic
      appearance in STM images. Due to their mobility on the Au(111) surface at room
      temperature, the molecules spontaneously formed self-organized molecular
      arrangements that reflected their chemical structure. While lateral displacement
      of the molecules was accomplished by manipulation, trans-cis isomerization
      processes, typical for azobenzene switches, could not be induced.

PMID- 22964492
TI  - Ileal conduit and continent ileocecal pouch for patients undergoing pelvic
      exenteration: comparison of complications and quality of life.
AB  - OBJECTIVES: Creating a continent urinary pouch has become an alternative to the
      ileal conduit for patients undergoing exenteration for advanced gynecologic
      malignancies. The objective of this study was to compare clinical outcomes for
      the 2 methods. METHODS: In this retrospective study, we compared intraoperative
      and postoperative complications and quality-of-life scores for the modified
      ileocecal pouch and the ileal conduit in anterior or total pelvic exenteration.
      RESULTS: In 33 of 100 patients, an ileal pouch (IP) was created; the other 67
      were treated by an ileal conduit (IC). Creating an IP prolonged the exenterative
      procedure by 97 minutes compared to an IC (IC, 453 minutes vs IP, 550 minutes; P
      = 0.009). Overall complication rates were similar, but patients with an IP had
      significantly more complications of urinary diversion (48%) than patients with an
      IC (31%; P = 0.03). Follow-up showed urinary loss and frequency of micturition to
      be comparable, but in patients with an IP, surgery for stomal complications (n =
      2) and treatment of bladderstones were necessary more frequently (n = 3). Quality
      of life according to the 12-item Short Form Health Survey questionnaire was
      similar in both groups. CONCLUSION: A continent IP is an alternative to the IC in
      cases of pelvic exenteration. Early complications are more frequent with an IP
      than with an IC. The mode of urinary diversion has little influence on the
      quality of life in patients with advanced genital cancer.

PMID- 22964493
TI  - The effect of electroacupuncture on insulin-like growth factor-I and oxidative
      stress in an animal model of renal failure-induced hypertension.
AB  - BACKGROUND/AIMS: The present study was performed to demonstrate the effect of
      electroacupuncture (EA) and acupuncture on renal failure (RF)-induced
      hypertension. METHODS: We stimulated the Zusanli (ST36) and Taixi (KI3) acupoints
      in a rat model of RF-induced hypertension. RESULTS: EA significantly reduced RF
      induced hypertension (p < 0.05). In a histopathological study, increments in RF
      induced glomerulosclerosis and tubulointerstitial fibrosis were attenuated by EA
      treatment (p < 0.05). The increase in albuminuria in the RF group was also
      reduced by EA treatment (p < 0.05). In blood analysis, the increment in RF
      induced serum BUN and creatinine concentrations were decreased by EA (p < 0.05),
      and the decreases in RF-induced insulin-like growth factor-I (IGF-I) mRNA and
      protein levels were increased by EA in both the kidney and the serum (p < 0.05).
      The increases in RF-induced oxidative stress, e.g. inducible nitric oxide
      synthase, heme oxygenase and thiobarbituric acid-reactive substance expression,
      were significantly decreased in the RF-EA group (p < 0.01). CONCLUSION: These
      findings suggest that the anti-hypertensive mechanism of EA could be related to
      the effects of oxidative stress on IGF-I in RF-induced hypertension.

PMID- 22964494
TI  - The new digital flexible ureteroscopes: 'size does matter'--increased ureteric
      access sheath use!
AB  - OBJECTIVES: To evaluate whether the use of sheaths to access the ureter has
      increased after the introduction of new digital ureterorenoscopes in patients
      undergoing flexible ureteroscopy. METHODS: 140 patients with kidney stones were
      randomised to be scoped with either an old-generation fibre-optic flexible
      ureteroscope (DUR-8, Elite, ACMI; distal tip diameter = 6.75 Fr) or a new
      generation digital LCD flexible ureteroscope (Invisio D-URD flexible
      ureteroscope; distal tip diameter = 8.7 Fr). We recorded the necessity to use a
      sheath to access the ureter, sheath-related and postoperative complications, and
      whether or not a JJ stent was left behind. RESULTS: 157 (80 fibre-optic and 77
      digital) ureterorenoscopies were performed. Ureteral access sheaths were used
      significantly more frequently with digital scopes (p = 0.00174). Two patients in
      the digital scope group had a small distal ureteric perforation from the
      introducer sheath compared with none in the fibre-optic scope group. CONCLUSIONS:
      A statistically significant increase in sheath use was observed in the new
      generation digital flexible ureteroscopy group. Despite the improvement in image
      quality, better durability and improved stone clearance, there are some potential
      drawbacks of these scopes. The increased distal tip diameter can result in
      increased use of ureteric access sheaths and this may increase morbidity and
      expense.

PMID- 22964495
TI  - Glutathione participates in the modulation of starvation-induced autophagy in
      carcinoma cells.
AB  - Glutathione (gamma-L-glutamyl-L-cysteinyl-glycine, GSH) is the most abundant low
      molecular weight, thiol-containing compound within the cells and has a primary
      role in the antioxidant defense and intracellular signaling. Here we demonstrated
      that nutrient deprivation led to a significant decrease of intracellular GSH
      levels in three different carcinoma cell lines. This phenomenon was dependent on
      ABCC1-mediated GSH extrusion, along with GCL inhibition and, to a minor extent,
      the formation of GSH-protein mixed disulfides that synergistically contributed to
      the modulation of autophagy by shifting the intracellular redox state toward more
      oxidizing conditions. Modulation of intracellular GSH by inhibiting its de novo
      synthesis through incubation with buthionine sulfoximine, or by maintaining its
      levels through GSH ethyl ester, affected the oxidation of protein thiols, such as
      PRDXs and consequently the kinetics of autophagy activation. We also demonstrated
      that thiol-oxidizing or -alkylating agents, such as diamide and diethyl maleate
      activated autophagy, corroborating the evidence that changes in thiol redox state
      contributed to the occurrence of autophagy.

PMID- 22964496
TI  - Symptom severity and guideline-based treatment recommendations for depressed
      patients: implications of DSM-5's potential recommendation of the PHQ-9 as the
      measure of choice for depression severity.

PMID- 22964497
TI  - Mesua beccariana (Clusiaceae), a source of potential anti-cancer lead compounds
      in drug discovery.
AB  - An investigation on biologically active secondary metabolites from the stem bark
      of Mesua beccariana was carried out. A new cyclodione, mesuadione, along with
      several known constituents which are beccamarin, 2,5-dihydroxy-1,3,4-trimethoxy
      anthraquinone, 4-methoxy-1,3,5-trihydroxyanthraquinone, betulinic acid and
      stigmasterol were obtained from this ongoing research. Structures of these
      compounds were elucidated by extensive spectroscopic methods, including 1D and 2D
      NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic
      activities of all the isolated metabolites against a panel of human cancer cell
      lines Raji (lymphoma), SNU-1 (gastric carcinoma), K562 (erythroleukemia cells),
      LS-174T (colorectal adenocarcinoma), HeLa (cervical cells), SK-MEL-28 (malignant
      melanoma cells), NCI-H23 (lung adenocarcinoma), IMR-32 (neuroblastoma) and Hep-G2
      (hepatocellular liver carcinoma) were carried out using an MTT assay. Mesuadione,
      beccamarin, betulinic acid and stigmasterol displayed strong inhibition of Raji
      cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were
      strongly inhibited by stigmasterol and beccamarin, indicating these secondary
      metabolites could be anti-cancer lead compounds in drug discovery.

PMID- 22964498
TI  - Photoelectrode characteristics of partially hydrolyzed aluminum phthalocyanine
      chloride/fullerene C60 composite nanoparticles working in a water phase.
AB  - Photoelectrochemical measurements were used to study the photoelectrode
      characteristics of composite nanoparticles composed of fullerene C60 and
      partially hydrolyzed aluminum phthalocyanine chloride (AlPc). In cyclic
      voltammetry measurements, the electrodes coated with the composite nanoparticles
      were found to have photoanodic [electron donor: 2-mercaptoethanol (ME)] and
      photocathodic (electron acceptor: O2) characteristics similar to those of the
      vapor-deposited p/n junction electrode. Their photoanodic features were further
      investigated with respect to the transient photocurrent response to light
      irradiation and the dependence on ME concentration (under potentiostatic
      conditions), from which it was noted that there was a decrease in the initial
      spiky photocathodic current and saturation of the steady-state photoanodic
      current at a higher ME concentration. Thus, the reaction kinetics was probably
      dominated by charge transport process. Moreover, external and internal quantum
      efficiency spectrum measurements indicated that the composite nanoparticles
      responded to the full spectrum of visible light ( < 880 nm) for both the
      photoanodic and photocathodic current. The present research will assist
      comprehension of photocatalytic behavior of the composite nanoparticles.

PMID- 22964499
TI  - Phorbol esters from Jatropha meal triggered apoptosis, activated PKC-delta,
      caspase-3 proteins and down-regulated the proto-oncogenes in MCF-7 and HeLa
      cancer cell lines.
AB  - Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia
      contains phorbol esters (PEs). The potential benefits of PEs present in the meal
      as anticancer agent are still not well understood. Hence, this study was
      conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated
      from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines.
      Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF
      7 and HeLa cell lines with the IC50 of 128.6 +/- 2.51 and 133.0 +/- 1.96 ug PMA
      equivalents/mL respectively, while the values for the phorbol 12-myristate 13
      acetate (PMA) as positive control were 114.7 +/- 1.73 and 119.6 +/- 3.73 ug/mL,
      respectively. Microscopic examination showed significant morphological changes
      that resemble apoptosis in both cell lines when treated with PEs and PMA at IC50
      concentration after 24 h. Flow cytometry analysis and DNA fragmentation results
      confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs
      isolated from Jatropha meal activated the PKC-delta and down-regulated the proto
      oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation
      of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell
      lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were
      found to be promising as an alternative to replace the chemotherapeutic drugs for
      cancer therapy.

PMID- 22964500
TI  - Protective effects of the key compounds isolated from Corni fructus against beta
      amyloid-induced neurotoxicity in PC12 cells.
AB  - beta-Amyloid (Abeta) peptide is the major component of senile plaques and is
      considered to have a causal role in the development and progression of
      Alzheimer's disease (AD). There is compelling evidence supporting the notion that
      Abeta-induced cytotoxicity is mediated though the generation of ROS. In the
      present study, we investigated the neuroprotective effects of ursolic acid (UA),
      p-coumaric acid (p-CA), and gallic acid (GA) isolated from Corni fructus (CF)
      against Abeta(25-35)-induced toxicity in PC12 cell. Exposure of PC12 cells to 50
      MUM Abeta(25-35) increased cellular oxidative stress, the number of apoptotic
      cells and caspase-3 activity and finally caused significant cell death. However,
      UA, p-CA, and GA not only suppressed the generation of ROS but also attenuated
      DNA fragmentation and eventually attenuated Abeta-induced apoptosis in a dose
      dependent manner. In protecting cells against Abeta neurotoxicity, UA and GA
      possessed stronger ability against ROS generation than p-CA, while p-CA showed
      the strongest anti-apoptotic activity. Particularly, p-CA protected cells at the
      concentration range from 0.5 up to 125 MUM without any adverse effect. Taken
      together, these effects of UA, p-CA, and GA may be partly associated with the
      neuroprotective effect of CF. Furthermore, our findings might raise a possibility
      of therapeutic applications of CF for preventing and/or treating
      neurodegenerative diseases.

PMID- 22964501
TI  - Synthesis and antibacterial activities of novel 4-hydroxy-7-hydroxy- and 3
      carboxycoumarin derivatives.
AB  - Coumarin derivatives are used as fluorescent dyes and medicines. They also have
      some notable physiological effects, including the acute hepatoxicity and
      carcinogenicity of certain aflatoxins, the anticoagulant action of dicoumarol,
      and the antibiotic activity of novobicin and coumerymycin A1. Because the number
      of drug resistant strains is increasing at present, the synthesis of new
      antibacterial compounds is one of the critical methods for treating infectious
      diseases. Therefore, a series of coumarinsubstituted derivatives, namely 4
      hydroxy- and 7-hydroxycoumarins, and 3-carboxycoumarins were synthesized. 4
      Hydroxycoumarin derivatives 4a-c underwent rearrangement reactions. Both 4- and 7
      hydroxycoumarins were treated with activated aziridines which produced series of
      ring-opened products 7, 8, 10, and 11. 3-Carboxy-coumarin amide dimer derivatives
      14-21 were prepared by reacting aliphatic alkylamines and alkyldiamines with
      PyBOP and DIEA. In this study, we use a new technique called modified micro-plate
      antibiotic susceptibility test method (MMAST), which is more convenient, more
      efficient, and more accurate than previous methods and only a small amount of the
      sample is required for the test. Some of the compounds were produced by reactions
      with acid anhydrides and demonstrated the ability to inhibit Gram-positive
      microorganisms. The dimer derivatives displayed lower antibacterial activities.

PMID- 22964502
TI  - Ultrasound irradiation promoted enzymatic transesterification of (R/S)-1-chloro-3
      (1-naphthyloxy)-2-propanol.
AB  - (R)-1-Chloro-3-(1-naphthyloxy)-2-propanol, which is the key intermediate of (S)
      propranolol, was successfully prepared via enantioselective transesterification
      catalyzed by lipase under ultrasound irradiation. Compared with conventional
      shaking, the enzyme activity and enantioselectivity were dramatically increased
      under ultrasound exposure. Effects of various reaction conditions on the
      synthetic activity of enzyme as well as enantioselectivity, including the type of
      enzyme, ultrasound power, solvent, acyl donor, temperature and substrate molar
      ratio, were investigated. Pseudomonas sp. lipase (PSL) showed an excellent
      catalytic performance under optimum conditions (enzyme activity: 78.3 +/- 3.2
      MUmol.g-1.min-1, E value: 98 +/- 6).

PMID- 22964503
TI  - Effect of different purification techniques on the characteristics of
      heteropolysaccharide-protein biopolymer from durian (Durio zibethinus) seed.
AB  - Natural biopolymers from plant sources contain many impurities (e.g., fat,
      protein, fiber, natural pigment and endogenous enzymes), therefore, an efficient
      purification process is recommended to minimize these impurities and consequently
      improve the functional properties of the biopolymer. The main objective of the
      present study was to investigate the effect of different purification techniques
      on the yield, protein content, solubility, water- and oil-holding capacity of a
      heteropolysaccharide-protein biopolymer obtained from durian seed. Four different
      purification methods using different chemicals and solvents (i.e., A (isopropanol
      and ethanol), B (isopropanol and acetone), C (saturated barium hydroxide), and D
      (Fehling solution)] to liberate the purified biopolymer from its crude form were
      compared. In most cases, the purification process significantly (p < 0.05)
      improved the physicochemical properties of heteropolysaccharide-protein
      biopolymer from durian fruit seed. The present work showed that the precipitation
      using isopropanol and acetone (Method B) resulted in the highest purification
      yield among all the tested purification techniques. The precipitation using
      saturated barium hydroxide (Method C) led to induce the highest solubility and
      relatively high capacity of water absorption. The current study reveals that the
      precipitation using Fehling solution (Method D) most efficiently eliminates the
      protein fraction, thus providing more pure biopolymer suitable for biological
      applications.

PMID- 22964504
TI  - Platelet-activating factor (PAF) antagonistic activity of a new biflavonoid from
      Garcinia nervosa var. pubescens King.
AB  - The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which
      showed strong inhibitory effects on platelet-activating factor (PAF) receptor
      binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid,
      II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together
      with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The
      structures of the compounds were elucidated by spectroscopic methods. The
      compounds were evaluated for their ability to inhibit PAF receptor binding to
      rabbit platelets using 3H-PAF as a ligand. The biflavonoid and acacetin showed
      strong inhibition with IC50 values of 28.0 and 20.4 uM, respectively. The results
      suggest that these compounds could be responsible for the strong PAF antagonistic
      activity of the plant.

PMID- 22964506
TI  - Brain imaging: measures of functional brain connectivity can be used to predict
      outcome after glioma surgery.

PMID- 22964505
TI  - The protective role of caffeic acid phenethyl ester against streptomycin
      ototoxicity.
AB  - OBJECTIVE: The aim of this experimental study was to investigate the efficacy of
      caffeic acid phenethyl ester (CAPE) in the prevention of streptomycin-induced
      ototoxicity. MATERIALS AND METHODS: Thirty-two adult Wistar albino rats were
      divided into 4 groups: control (n = 8), streptomycin (n = 8), CAPE (n = 8), and
      streptomycin + CAPE (n = 8). Rats were tested with distortion product otoacoustic
      emissions (DPOAEs) before drug administration. The animals in all groups were
      killed under general anesthesia on the 45th day following last DPOAE
      measurements. Hearing results were analyzed statistically to determine
      differences in amplitudes of DPOAE. Also, the cochleas of each rat were evaluated
      by histopathological and immunohistochemical examination. RESULTS: Significant
      difference was not observed in cochlear hair cells in the control and CAPE
      groups. In the streptomycin group, severe degeneration of hair cells and
      increased apoptotic cells were observed. In the streptomycin + CAPE group,
      although some deteriorations were observed, hair cells were mostly preserved. The
      DPgram of the streptomycin and streptomycin + CAPE groups was significantly
      deteriorated (P < .05). The analysis of the DPgram results revealed statistically
      significant differences between the groups of streptomycin and streptomycin +
      CAPE (P < .05). CONCLUSIONS: Caffeic acid phenethyl ester treatment attenuated
      hair cells injury in the inner ear, possibly via its antioxidant effect.
      Prophylactic administration of CAPE for streptomycin ototoxicity ameliorated
      hearing deterioration in rats.

PMID- 22964508
TI  - Traumatic brain injury: tissue-type plasminogen activator--harmful or beneficial?

PMID- 22964510
TI  - Pharmacoresistance and the role of surgery in difficult to treat epilepsy.
AB  - Pharmacoresistance occurs in up to 30% of patients with epilepsy, and is most
      commonly associated with epilepsy of structural or metabolic origin, abnormal
      findings on brain imaging or examination, and failure to respond to the first two
      antiepileptic drugs. However, in patients presumed to have difficult to treat
      epilepsy, factors that might result in apparent treatment resistance
      (misdiagnosis of epilepsy, incorrect drug and/or dose, and lifestyle issues) must
      first be excluded and the diagnosis re-examined. Epilepsy is commonly
      misdiagnosed, especially in patients with syncope and psychogenic events. The
      initial steps in confirming the diagnoses of both epilepsy and pharmacoresistance
      are to obtain a detailed, reliable history and to conduct a careful review of all
      prior trials of antiepileptic drug therapy. Once the diagnoses of epilepsy and
      pharmacoresistance are confirmed, the seizure type, epilepsy syndrome, and
      expected course of the disorder dictate its medical and surgical management.
      Epilepsy surgery should be considered promptly in these patients, since few
      interventions are as effective as brain surgery in this setting, particularly in
      patients with focal pharmacoresistant epilepsy. This Review discusses the concept
      of pharmacoresistance and describes the approach to management of the patient
      with difficult to treat epilepsy, focusing on the important role of epilepsy
      surgery.

PMID- 22964514
TI  - Disease mechanisms in MS: phases of disease improvement unrelated to relapses.
AB  - Natural history of multiple sclerosis includes phases of relapse, remission and
      insidious progression. New data show that sustained improvements in disease,
      defined by reductions in EDSS scores, occur independent of relapses almost half
      as frequently as disease worsening. This finding might facilitate research into
      the biological processes involved in disease improvement.

PMID- 22964515
TI  - Isoelectric reference for pericarditis: TP may be better than PR.

PMID- 22964509
TI  - Neurocognitive function after radiotherapy for paediatric brain tumours.
AB  - The brain is highly vulnerable to neurotoxic agents during the prime learning
      period of a child's life. Paediatric patients with brain tumours who are treated
      with cranial radiation therapy (CRT) often go on to develop neurocognitive
      deficits, which are reflected in poor academic achievement and impaired memory,
      attention and processing speed. The extent of these delayed effects varies with
      radiation dose, brain volume irradiated, and age at treatment, and might also be
      influenced by genetic factors and individual susceptibility. CRT-induced
      impairment involves axonal damage and disruption of white matter growth, and can
      affect brain structures implicated in memory function and neurogenesis, such as
      the hippocampus. In this article, we review the underlying mechanisms and
      clinical consequences of CRT-induced neurocognitive damage in survivors of
      paediatric brain tumours. We discuss the recent application of neuroimaging
      technologies to identify white matter injury following CRT, and highlight new
      radiation techniques, pharmacological and neurological interventions, as well as
      rehabilitation programmes that have potential to minimize neurocognitive
      impairment following CRT.

PMID- 22964516
TI  - In vitro investigation of integrin-receptor antagonist-induced vascular toxicity
      in the mouse.
AB  - An alphaVbeta3 receptor antagonist (SB-273005) induced unique vascular lesions in
      the aorta of mice, but not other pharmacologically responsive species. Vascular
      smooth muscle cell (VSMC) necrosis was observed ~6 h postdose followed by VSMC
      loss with no evidence of hemorrhage/thrombosis, inflammation or damage to
      endothelium. Since direct drug-induced vascular toxicity is uncommon, involvement
      of VSMC-endothelial cell (EC) interactions was hypothesized. In vitro model
      systems of murine aortic VSMC and EC monocultures and cocultures were established
      and used to investigate the mechanism of toxicity. Incubation of cultures with SB
      273005 within a dose range and timeframe comparable to in vivo studies, showed a
      concentration-dependent decrease in viability with increases in cytotoxicity for
      monocultures and VSMC/EC cocultures; however, VSMC monocultures responded at
      lower doses (were most sensitive) suggesting a direct effect on VSMC which is not
      mediated or enhanced through EC/VSMC interactions. Further studies revealed
      increased caspase-9 and caspase-3/7 activation in VSMC beginning as early as 0.5
      and 1h following treatment, respectively. These findings suggest SB-273005 causes
      direct chemical vascular toxicity in murine VSMC which involves apoptosis
      mediated through the intrinsic (mitochondrial) apoptotic pathway. To our
      knowledge, this is the first report to provide a link between VSMC apoptosis and
      treatment with an alphaVbeta3 receptor antagonist.

PMID- 22964517
TI  - Intrahepatic transplantation of cord blood CD34+ cells into newborn NOD/SCID
      IL2Rgamma(null) mice allows efficient multi-organ and multi-lineage hematopoietic
      engraftment without accessory cells.

PMID- 22964518
TI  - Pulse corticosteroid therapy for alopecia areata: long-term outcome after 10
      years.
AB  - BACKGROUND: Few data are available concerning the efficiency of pulse
      corticosteroids in alopecia areata (AA). OBJECTIVE: Our purpose was to assess the
      long-term outcomes of patients treated with methylprednisolone bolus. METHODS:
      This study included 60 patients treated between 1995 and 2000. The short-term
      outcomes were analyzed in 2000. The long-term assessment of 30 patients was
      performed in 2010 by phone questionnaire. RESULTS: Significant hair regrowth was
      observed in 10/30 patients at 6 months after the bolus treatment. Half of the
      plurifocalis AA patients were responders at 6 months, but less than one quarter
      of alopecia totalis (AT) and alopecia universalis (AU) patients responded. Long
      term outcomes were assessed after a mean duration of 12.3 years; 8/10 initial
      responders had mild or no disease, and 14/20 initial nonresponders had severe AA.
      CONCLUSIONS: This study confirmed the low efficiency, both short- and long-term,
      of this treatment for AT and AU.

PMID- 22964519
TI  - Infection, inflammation and colon carcinogenesis.

PMID- 22964520
TI  - Preparing and regulating a bi-stable molecular switch by atomic manipulation.
AB  - We present a scanning tunneling microscopy (STM) investigation into the influence
      of the STM tip on the adsorption site switching of polychlorinatedbiphenyl (PCB)
      molecules on the Si(111)-7 * 7 surface at room temperature. From an initially
      stable adsorption configuration, atomic manipulation by charge injection from the
      STM tip prepared a new bi-stable configuration that switched between two bonding
      arrangements. No switching rate bias dependence was found for +1.0 to +2.2 V.
      Assuming a thermally driven switching process we find that the measured energy
      barriers to switching are influenced by the exact location of the STM tip by more
      than 10%. We propose that this energy difference is due the dispersion
      interaction between the tip and the molecule.

PMID- 22964521
TI  - Bacterial quorum sensing: functional features and potential applications in
      biotechnology.
AB  - Quorum sensing (QS) represents an exceptional pattern of cell-to-cell
      communication in bacteria using self-synthesized signalling molecules known as
      autoinducers. Various features regulated by QS in bacteria include virulence,
      biofilm formation, sporulation, genetic competence and bioluminescence, among
      others. Other than the diverse signalling properties of autoinducers, there are
      non-signalling properties also associated with these signalling molecules which
      make them potential antimicrobial agents and metal chelators. Additionally, QS
      signal antagonism has also been shown to be a promising alternative for blocking
      pathogenic diseases. Besides, QS has impressive design features useful in tissue
      engineering and biosensor technology. Although many aspects of QS are well
      understood, several other features remain largely unknown, especially in
      biotechnology applications. This review focuses on the functional features and
      potential applications of QS signalling molecules in biotechnology.

PMID- 22964522
TI  - Clinimetrics and clinical psychometrics: macro- and micro-analysis.
AB  - BACKGROUND: Clinimetrics was introduced three decades ago to specify the domain
      of clinical markers in clinical medicine (indexes or rating scales). In this
      perspective, clinical validity is the platform for selecting the various indexes
      or rating scales (macro-analysis). Psychometric validation of these indexes or
      rating scales is the measuring aspect (micro-analysis). METHODS: Clinical
      judgment analysis by experienced psychiatrists is included in the macro-analysis
      and the item response theory models are especially preferred in the micro
      analysis when using the total score as a sufficient statistic. RESULTS: Clinical
      assessment tools covering severity of illness scales, prognostic measures, issues
      of co-morbidity, longitudinal assessments, recovery, stressors, lifestyle,
      psychological well-being, and illness behavior have been identified. CONCLUSION:
      The constructive dialogue in clinimetrics between clinical judgment and
      psychometric validation procedures is outlined for generating developments of
      clinical practice in psychiatry.

PMID- 22964523
TI  - Laparoscopic nerve-sparing radical parametrectomy for occult early-stage invasive
      cervical cancer after simple hysterectomy.
AB  - OBJECTIVE: To investigate the feasibility and surgical outcomes of laparoscopic
      nerve-sparing radical parametrectomy (LNSRP) and lymphadenectomy for treatment of
      occult early-stage invasive cervical cancer after simple hysterectomy. METHODS:
      From 2006 to 2010, 28 patients who were discovered to have occult early-stage
      invasive cervical cancer after a simple hysterectomy underwent LNSRP, upper
      vaginal resection, and pelvic lymphadenectomy. A retrospective analysis of these
      cases was performed. RESULTS: All patients underwent successful LNSRP. There was
      no conversion to laparotomy. The mean +/- SD operation time was 173.30 +/- 56.20
      minutes. The mean +/- SD estimated blood loss was 230.00 +/- 109.55 mL. Two
      intraoperative complications were recorded. The median number of extracted pelvic
      and para-aortic lymph nodes was 23 (range, 12-36) and 7 (range, 3-15),
      respectively. The mean +/- SD time before Foley catheter removal was 5.6 +/- 2.74
      days (range, 3-14 days ), and bladder voiding function recovery to grade 0 to
      grade 1 was observed in 26 patients (92.9%). Of the 28 patients, 3 patients
      received further adjuvant therapy. The median follow-up period was 38 (range, 4
      62) months for all patients. No recurrence case was found in this series.
      CONCLUSION: Laparoscopic nerve-sparing radical parametrectomy is a therapeutic
      option for occult early-stage invasive cervical cancer discovered after
      hysterectomy. Nerve-sparing radical surgery in indicated patients may lead to
      optimal preservation of bladder function.

PMID- 22964524
TI  - Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in
      endometrial cancer.
AB  - BACKGROUND: Lymph node involvement is a major feature in tumor spread of
      endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel
      invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of
      great importance. Immunostaining of D2-40 (podoplanin), a specific marker for
      lymphatic endothelial cells, might be able to increase the detection rate of LVI
      compared with conventional hematoxylin-eosin (H-E) staining. The aim of this
      retrospective study was to analyze the eligibility of D2-40-based LVI evaluation
      for the prediction of lymph node metastases and patients' outcome. PATIENTS AND
      METHODS: Immunohistochemical staining with D2-40 monoclonal antibodies was
      performed on paraffin-embedded tissue sections of 182 patients with primary
      endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were
      screened for the presence of LVI. Correlations with clinicopathological features
      and clinical outcome were assessed. RESULTS: Immunostaining of D2-40
      significantly increased the frequency LVI detection compared with conventional H
      E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182
      tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P =
      0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and
      significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI
      was an independent prognostic factor for patients overall survival considering
      tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40
      negative tumors confined to the inner half of the myometrium showed an excellent
      outcome (5-year overall survival, 97.8%). CONCLUSIONS: D2-40-based LVI assessment
      improves the histopathological detection of lymphovascular invasion in
      endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph
      node metastasis. D2-40 LVI detection might help to select endometrial cancer
      patients who will benefit from a lymphadenectomy.

PMID- 22964525
TI  - Matrix metalloproteinase (MMP)-2 and MMP-9 expression in tumor infiltrating CD3
      lymphocytes from women with endometrial cancer.
AB  - OBJECTIVE: In this study, we hypothesized that not only endothelial malignant
      cells but also lymphocytes infiltrating tumor epithelium, in patients with
      endometrial cancer, could be an important source of the gelatinases (matrix
      metalloproteinase [MMP]-2 and MMP-9) extensive production, which in turn, may
      facilitate tumor cells infiltration and progression due to the extracellular
      matrix degradation. MATERIALS AND METHODS: First, we isolated lymphocytes from
      the endometrial carcinoma samples taken from 41 patients who were operated on and
      from healthy endometrial tissue taken of the same patients after histological
      verification. Then, we detected the level of CD3-positive cells in endometrial
      tissues by flow cytometry. Simultaneously, we studied the messenger RNA
      expression of MMP-2 and MMP-9 in the isolated cells from malignant and unchanged
      endometrial tissues. Using immunohistochemistry, we compared the protein
      expression of MMP-2, MMP-9, and CD3 in the studied samples. RESULTS: We showed
      the enhanced abundance of CD3 lymphocytes both by flow cytometry and
      immunohistochemistry in the samples from malignant tissues. The expression of MMP
      9 in the endometrial carcinoma was increased significantly at the protein level
      but not at the messenger RNA level. We could not observe any differences
      concerning MMP-2 expression in both methods of detection. CONCLUSIONS: CD-3
      lymphocytes significantly infiltrate endometrial cancer tissue, but they do not
      seem to be the source of enhanced metalloproteinases 2 and 9 expression in the
      tumor environment. Still, owing to the immunohistochemistry staining, we could
      show the significant increase of MMP-9 protein in the very close vicinity of
      tumor-infiltrating CD3 lymphocytes. Could it be the result of CD3 lymphocyte
      action, or is it just the imperfection of the detecting method we used? This
      remains unclear. Further studies explaining the role of tumor infiltrating
      lymphocytes in mediating the endometrial cancer milieu are needed.

PMID- 22964526
TI  - Determinants of lymph node count in endometrial cancer surgical staging.
AB  - OBJECTIVE: Lymphadenectomy is a fundamental procedure in gynecologic oncology,
      but there is an ongoing debate concerning its indication in endometrial cancer.
      Lymph node (LN) count has been used as a surrogate marker for quality of staging
      in endometrial cancer. Because of variability in reported LN counts in the
      literature and within our practice, we aimed to better understand the factors
      that influence the final LN count in endometrial cancer staging. METHODS: We
      conducted a retrospective case study of patients with endometrial cancer who
      underwent surgical staging at our institution between April 1, 2005, and February
      3, 2007. Linear regression was used to determine the association between LN count
      and a series of predictor variables. RESULTS: Of 131 patients, 100 patients (76%)
      had stage I disease and 9 patients (7%) had LN metastasis. The mean (SD) LN count
      was 9.5 (7.8). We found no significant difference in LN count according to age,
      tumor histology, stage, or surgeon. Lymph node count decreased by 1 for each 5
      unit (kg/m(2)) increase in body mass index (coefficient, -0.2; P = 0.038). The
      strongest predictor associated with LN count was the pathologist, with 2 groups
      of pathologists counting an average 7.7 (P < 0.001) and 6.42 (P = 0.001) fewer
      LNs per case compared to the referent group. CONCLUSIONS: Our study confirms that
      LN count varies markedly. Although not the only contributor, the pathologist, we
      found, was the most significant determining factor in LN count variation. This
      highlights the need to exercise caution when drawing conclusions from published
      LN counts in endometrial cancer research.

PMID- 22964527
TI  - Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian,
      fallopian, and peritoneal cancer in day-to-day practice: a Retrospective French
      Multicentric Study.
AB  - OBJECTIVES: To evaluate the outcome of maximal cytoreductive surgery in patients
      with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding
      overall survival (OS) and disease-free survival (DFS). MATERIALS AND METHODS:
      Five hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV
      (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery
      between January 2003 and December 2007 in 7 gynecologic oncology centers in
      France. Patients undergoing primary and interval debulking surgery were included,
      whichever the number of chemotherapy cycles. The extent of disease, type of
      surgical procedure, and amount of residual disease were recorded. A multivariate
      analysis of the outcome was performed, taking into account the stage, grade, and
      timing of surgery. RESULTS: Median DFS was 17.9 months, but median OS was not
      reached at the time of analysis. Complete cytoreductive surgery, without evident
      residual tumor at the end of the procedure, was obtained in 71% of all patients
      (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking
      surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty
      three percent of patients needed "ultra radical surgery" to achieve this goal.
      The most significant predictive factor for DFS and OS was complete cytoreductive
      surgery compared to any amount, even minimal (1-10 mm), of residual disease. In
      the group of patients with complete cytoreductive surgery, the patients
      undergoing surgery before chemotherapy showed better DFS than those having first
      chemotherapy. CONCLUSION: The findings confirm that complete cytoreduction is the
      criterion standard of surgery in the management of advanced ovarian, peritoneal,
      and fallopian tube cancer, whatever the timing of surgery. With experienced
      teams, surgery was completed, without evident residual tumor in 71% of the cases.

PMID- 22964528
TI  - Measuring the methylome in clinical samples: improved processing of the Infinium
      Human Methylation450 BeadChip Array.
AB  - The Infinium Human Methylation450 BeadChip Array (TM)  (Infinium 450K) is an
      important tool for studying epigenetic patterns associated with disease. This
      array offers a high-throughput, low cost alternative to more comprehensive
      sequencing-based methodologies. Here we compare data generated by interrogation
      of the same seven clinical samples by Infinium 450K and reduced representation
      bisulfite sequencing (RRBS). This is the largest data set comparing Infinium 450K
      array to the comprehensive RRBS methodology reported so far. We show good
      agreement between the two methodologies. A read depth of four or more reads in
      the RRBS data was sufficient to achieve good agreement with Infinium 450K.
      However, we observe that intermediate methylation values (20-80%) are more
      variable between technologies than values at the extremes of the bimodal
      methylation distribution. We describe careful processing of Infinium 450K data to
      correct for known limitations and batch effects. Using methodologies proposed by
      others and newly implemented and combined in this report, agreement of Infinium
      450K data with independent techniques can be vastly improved.

PMID- 22964529
TI  - Evolution of melanocortin receptors in cartilaginous fish: melanocortin receptors
      and the stress axis in elasmobranches.
AB  - There is general agreement that the presence of five melanocortin receptor genes
      in tetrapods is the result of two genome duplications that occurred prior to the
      emergence of the gnathostomes, and at least one local gene duplication that
      occurred early in the radiation of the ancestral gnathostomes. Hence, it is
      assumed that representatives from the extant classes of gnathostomes (i.e.,
      Chondrichthyes, Actinopterygii, Sarcopterygii) should also have five paralogous
      melanocortin genes. Current studies on cartilaginous fishes indicate that while
      there is evidence for five paralogous melanocortin receptor genes in this class,
      to date all five paralogs have not been detected in the genome of a single
      species. This mini-review will discuss the ligand selectivity properties of the
      melanocortin-3 receptor of the elephant shark (subclass Holocephali) and the
      ligand selectivity properties of the melanocortin-3 receptor, melanocortin-4
      receptor, and the melanocortin-5 receptor of the dogfish (subclass
      Elasmobranchii). The potential relationship of these melanocortin receptors to
      the hypothalamus/pituitary/interrenal axis will be discussed.

PMID- 22964530
TI  - Insulin-like and testis ecdysiotropin neuropeptides are regulated by the
      circadian timing system in the brain during larval-adult development in the
      insect Rhodnius prolixus (Hemiptera).
AB  - Insulin-like peptides (ILPs) regulate numerous functions in insects including
      growth, development, carbohydrate metabolism and female reproduction. This paper
      reports the immunohistochemical localization of ILPs in brain neurons of Rhodnius
      prolixus and their intimate associations with the brain circadian clock system.
      In larvae, three groups of neurons in the protocerebrum are ILP-positive, and
      testis ecdysiotropin (TE) is co-localized in two of them. During adult
      development, the number of ILP groups increased to four. A blood meal initiates
      transport and release of ILPs, indicating that release is nutrient dependent.
      Both production and axonal transport of ILPs continue during adult development
      with clear cytological evidence of a daily rhythm that closely correlates with
      the daily rhythm of ILPs release from brains in vitro. The same phenomena were
      observed with TE previously. Double labeling for ILPs and pigment dispersing
      factor (PDF) (contained in the brain lateral clock cells, LNs) revealed intimate
      associations between axons of the ILP/TE cells and PDF-positive axons in both
      central brain and retrocerebral complex, revealing potential neuronal pathways
      for circadian regulation of ILPs and TE. Similar close associations were found
      previously between LN axons and axons of the brain neurons producing the
      neuropeptide prothoracicotropic hormone. Thus, the brain clock system controls
      rhythmicity in multiple brain neurohormones. It is suggested that rhythms in
      circulating ILPs and TE act in concert with known rhythms of circulating
      ecdysteroids in both larvae and adults to orchestrate the timing of cellular
      responses in diverse tissues of the animal, thereby generating internal temporal
      order within it.

PMID- 22964531
TI  - Sexually dimorphic expression of receptor-alpha in the cerebral cortex of
      neonatal Caiman latirostris (Crocodylia: Alligatoridae).
AB  - In mammals, estrogens have been described as endocrine and paracrine modulators
      of neuronal differentiation and synapse formation. However, the functional role
      of circulating estrogens and the distribution of estrogen receptors (ERs) in the
      cerebral cortex of reptiles have not been clearly established. Caiman latirostris
      (C. latirostris) is a South American species that presents temperature-dependent
      sex determination (TSD). By using immunohistochemistry, we have studied the
      distribution of ERalpha in the cerebral cortex of neonatal caimans. We studied
      brain samples from ten-day-old TSD-females and TSD-males and from female caimans
      that were administered estradiol during embryonic development (hormone-dependent
      sex determination, HSD-females). ERalpha was detected in the medial (MC), dorsal
      (DC) and lateral (LC) cortices. ERalpha expression in the MC showed sex
      associated differences, being significantly greater in TSD-females compared to
      TSD-males. Interestingly, the highest ERalpha expression in the MC was exhibited
      by HSD-females. In addition, the circulating levels of estradiol were
      significantly higher in females (both TSD and HSD) than in TSD-males. Double
      immunostaining showed that ERalpha is expressed by neural precursor cells (as
      detected by ERalpha/doublecortin or ERalpha/glial fibrillary acidic protein) and
      mature neurons (ERalpha/neuron-specific nuclear protein). Our results demonstrate
      that the expression of ERalpha in the neonatal caiman cortex is sexually
      dimorphic and is present in the early stages of neuronal differentiation.

PMID- 22964532
TI  - Severity scoring system for paediatric FMF.

PMID- 22964534
TI  - Rheumatoid arthritis: Threshold for success in RA drug development.
AB  - Determining the potential success of investigational therapies for rheumatoid
      arthritis early in the development process would enable better allocation of
      increasingly limited resources. Such 'go or no-go' decision-making could be
      improved by a method of analysing longitudinal clinical trial data to establish a
      threshold for success of a new drug.

PMID- 22964536
TI  - Osteoarthritis: Is viscosupplementation really so unsafe for knee OA?

PMID- 22964539
TI  - Preoperative predictors of pathologic stage T2a in low-risk prostate cancer:
      implications for focal therapy.
AB  - OBJECTIVE: To assess preoperative parameters that may be predictive of pathologic
      stage T2a disease in low-risk prostate cancer patients. METHODS: Data from a
      cohort of 1,495 consecutive men with low-risk prostate cancer who underwent a
      radical prostatectomy between 1993 and 2009 were evaluated. Preoperative
      parameter assessment focused on age, race, clinical stage, diagnostic PSA level,
      biopsy tumor laterality and diagnostic Gleason score. Preoperative parameters
      were analyzed by univariate and multivariate methods. Kaplan-Meier method was
      used to evaluate the biochemical disease-free survival. RESULTS: Among the 1,495
      men, 236 (15.8%) had pT2a disease. In univariate analysis, biopsy tumor
      unilaterality (p < 0.001), diagnostic PSA <= 4 ng/ml (p < 0.001) and non-African
      American race (p = 0.009) were significant variables. In multivariate analysis,
      biopsy tumor laterality (OR 0.377; p < 0.001), diagnostic PSA <= 4 ng/ml (OR
      0.621; p = 0.002) and race (OR 0.583; p = 0.029) were independent predictors. Low
      risk patients with pT2a disease showed a better PSA recurrence-free survival
      rate, compared with men with >pT2a diseases (p = 0.012). CONCLUSIONS: Biopsy
      tumor unilaterality, diagnostic PSA <= 4 ng/ml and race are independent
      predictors of pT2a in low-risk prostate cancer. These three preclinical variables
      may be a useful reference to begin the selection process for focal therapy in men
      with low-risk prostate cancer.

PMID- 22964540
TI  - Internet-based psychodynamic versus cognitive behavioral guided self-help for
      generalized anxiety disorder: a randomized controlled trial.
AB  - BACKGROUND: Guided Internet-based cognitive behavior therapy (ICBT) has been
      tested in many trials and found to be effective in the treatment of anxiety and
      mood disorders. Generalized anxiety disorder (GAD) has also been treated with
      ICBT, but there are no controlled trials on guided Internet-based psychodynamic
      treatment (IPDT). Since there is preliminary support for psychodynamic treatment
      for GAD, we decided to test if a psychodynamically informed self-help treatment
      could be delivered via the Internet. The aim of the study was to investigate the
      efficacy of IPDT for GAD and to compare against ICBT and a waiting list control
      group. METHOD: A randomized controlled superiority trial with individuals
      diagnosed with GAD comparing guided ICBT (n = 27) and IPDT (n = 27) against a no
      treatment waiting list control group (n = 27). The primary outcome measure was
      the Penn State Worry Questionnaire. RESULTS: While there were no significant
      between-group differences immediately after treatment on the main outcome
      measure, both IPDT and ICBT resulted in improvements with moderate to large
      within-group effect sizes at 3 and 18 months follow-up on the primary measure in
      the completer analyses. The differences against the control group, although
      smaller, were still significant for both PDT and CBT when conforming to the
      criteria of clinically significant improvement. The active treatments did not
      differ significantly. There was a significant group by time interaction regarding
      GAD symptoms, but not immediately after treatment. CONCLUSIONS: IPDT and ICBT
      both led to modest symptom reduction in GAD, and more research is needed.

PMID- 22964541
TI  - The hitchhiker's guide to virotherapy.

PMID- 22964542
TI  - Electrotransformation and expression of cellulase genes in wild-type
      Lactobacillus reuteri.
AB  - Two cellulase genes, Cel15 and Cel73, were amplified from Bacillus subtilis
      genome DNA in a previous study. Two integrative vectors, pLEM4153 and pLEM4154,
      containing the genes Cel15 and Cel73, respectively, were constructed and
      successfully electroporated into the wild-type Lactobacillus reuteri which was
      isolated from chick guts through an optimized procedure. Two recombinant L.
      reuteri were selected from a Man, Rogosa, and Sharp (MRS) plate with 10 ug/ml
      erythromycin, and named L. reuteri XNY-Cel15 and L. reuteri XNY-Cel73,
      respectively. To verify the transcription and expression of the two cellulase
      genes in the recombinant L. reuteri strains, the mRNA relative quantity (RQ) and
      the cellulase activity were determined. The mRNA RQ of Cel15 in L. reuteri XNY
      Cel15 is 1,8849.5, and that of Cel73 in L. reuteri XNY-Cel73 is 1,388, and the
      cellulase activity of the modified MRS broth cultured with L. reuteri XNY-Cel15
      was 0.158 U/ml, whereas that with L. reuteri XNY-Cel73 was 0.15 U/ml.

PMID- 22964543
TI  - Fatigue, brain, behavior, and immunity: summary of the 2012 Named Series on
      fatigue.
AB  - The focus on fatigue for the 2012 Named Series in brain, behavior, and immunity
      reflects the growing wave of research examining immune underpinnings of fatigue
      in healthy and clinical populations. Fatigue is prevalent in the general
      population and in patients with a variety of medical conditions. However, the
      etiology of fatigue remains elusive. Psychoneuroimmunological approaches to
      fatigue have yielded important advances in our understanding of this complex
      symptom and are represented in the twelve articles included in the Named Series.
      These articles include animal and human models of fatigue and cross a variety of
      different medical conditions, including cancer, chronic fatigue syndrome, and
      diabetes. This review briefly summarizes the articles included in the series and
      highlights the themes that have emerged from this body of work.

PMID- 22964544
TI  - Stress-evoked sterile inflammation, danger associated molecular patterns (DAMPs),
      microbial associated molecular patterns (MAMPs) and the inflammasome.
AB  - Since the inception of the field of psychoneuroimmunolology research, there has
      been an appreciation that the physiological response to stressors includes
      modulation of immune function. Investigators initially focused on the effect of
      stress on cellular migration and immunosuppression and the resultant decreases in
      tumor surveillance, anti-viral T cell immunity and antigen-specific antibody
      responses. More recently, it has become clear that exposure to stressors also
      potentiate innate immune processes. Stressor exposure, for example, can change
      the activation status of myeloid lineage cells such as monocytes, macrophages,
      neutrophils, and microglia, leading to a primed state. In addition, stressor
      exposure increases the synthesis and release of a vast cadre' of inflammatory
      proteins both in the blood and within tissues (i.e., spleen, liver, adipose,
      vasculature and brain). The mechanisms for stress-evoked innate immune 'arousal'
      remain unknown. The goals of this presidential address are the following: (1)
      offer a personalized, brief overview of stress and immunity with a focus on
      'aroused' innate immunity; (2) describe sterile inflammatory processes and the
      role of the inflammasome; and (3) suggest that these same processes likely
      contribute to primed myeloid cells and inflammatory protein responses (systemic
      and tissue) produced by stress in the absence of pathogens.

PMID- 22964545
TI  - Retraction statement. Paper by Kang et al. [Digestion 2012;85:33-39].

PMID- 22964546
TI  - Frontiers in Molecular Main Group Chemistry: a web themed issue.

PMID- 22964547
TI  - Mixed self-assembled monolayers of azobenzene photoswitches with trifluoromethyl
      and cyano end groups.
AB  - Mixed self-assembled monolayers (SAMs) of alkanethiolates carrying azobenzene
      chromophores with either a trifluoromethyl or a cyano substituent have been
      studied. High-resolution x-ray photoelectron spectroscopy proves that the ratio
      of adsorbed molecules can be arbitrarily adjusted via the molar fractions in
      solution. As a function of these molar fractions core level shifts are observed
      which are attributed to local work-function changes. By simulating the electric
      dipole field distribution, the continuous core level shifts are ascribed to a
      homogeneous mixture of molecules with different end groups adsorbed on adjacent
      lattice sites. Near-edge x-ray absorption fine structure measurements reveal
      formation of well-ordered SAMs. Despite the difference in dipole moment of the
      end groups, the molecular tilt and twist angles are identical for both single
      component SAMs and a 1:1 mixed SAM.

PMID- 22964548
TI  - Burn disaster response planning in New York City: updated recommendations for
      best practices.
AB  - Since its inception in 2006, the New York City (NYC) Task Force for Patients with
      Burns has continued to develop a city-wide and regional response plan that
      addressed the triage, treatment, transportation of 50/million (400) adult and
      pediatric victims for 3 to 5 days after a large-scale burn disaster within NYC
      until such time that a burn center bed and transportation could be secured. The
      following presents updated recommendations on these planning efforts. Previously
      published literature, project deliverables, and meeting documents for the period
      of 2009-2010 were reviewed. A numerical simulation was designed to evaluate the
      triage algorithm developed for this plan. A new, secondary triage scoring
      algorithm, based on co-morbidities and predicted outcomes, was created to
      prioritize multiple patients within a given acuity and predicted survivability
      cohort. Recommendations for a centralized patient and resource tracking database,
      plan operations, activation thresholds, mass triage, communications, data flow,
      staffing, resource utilization, provider indemnification, and stakeholder roles
      and responsibilities were specified. Educational modules for prehospital
      providers and nonburn center nurses and physicians who would provide interim care
      to burn injured disaster victims were created and pilot tested. These updated
      best practice recommendations provide a strong foundation for further planning
      efforts, and as of February 2011, serve as the frame work for the NYC Burn Surge
      Response Plan that has been incorporated into the New York State Burn Plan.

PMID- 22964549
TI  - Pressure ulcers and risk assessment in severe burns.
AB  - Risk and incidence of pressure ulcers (PUs) in the burn population remain poorly
      understood. The purpose of this study was to determine the timing and incidence
      of PUs at our regional burn center and to identify early risk factors for PU
      development in burn patients. A retrospective review of 40 charts was performed
      from among the 1489 patients admitted to our regional burn center between January
      2008 and December 2009. Twenty patients acquired PUs during their admission and
      were identified on the basis of International Classification of Diseases, ninth
      revision, designation, hospital stay >7 days, and thermal injury (excluding toxic
      epidermal necrolysis and purpura fulminans). The remaining 20 patients were
      matched controls based on +/-5 years in age and +/-8% TBSA. Patient, injury, and
      outcome characteristics were compared among patient groups using chi for
      categorical variables and Mann-Whitney for continuous variables. The incidence of
      PU was 1.3% of all admissions. PU most commonly occurred at the sacrum/coccyx
      (eight), lower extremity (seven), and occiput (six). A majority of PU presented
      at stage 2 (33%), stage 3 (26%), and unstageable (30%). Thirteen were splint or
      device related and reportable. Ninety percent of patients with PUs presented with
      a Braden score of 16 or less (P = .03), although 60% of controls also had
      admission Braden scores less than 16. On an average, PUs were acquired within 17
      days of admission. Data suggest burn patients are particularly at risk of
      developing PU based on admission Braden scores. However, low Braden scores do not
      necessarily correlate with eventual development of PU. Therefore, early and
      aggressive PU prevention and risk assessment tools must be used to diagnose PUs
      at an early and reversible stage.

PMID- 22964550
TI  - Clinico-epidemiological profile of burn patients admitted in a tertiary care
      hospital in coastal South India.
AB  - Every year a substantial proportion of deaths in India occur due to burn
      injuries. Prolonged morbidity as well as temporary and permanent disability due
      to burns results in a heavy economic loss. The etiological factors of burn
      injuries vary considerably in different communities and regions and hence the
      need for detailed epidemiological studies to understand the problem status in
      different regions. This study was aimed to study the sociodemographic profile of
      burn patients and to evaluate the causes, manner, and place of occurrence of
      burns injuries along with its outcome. A registry-based retrospective study was
      conducted at a tertiary care hospital in coastal South India, and the medical
      records of all the patients admitted to the burns centre during the year 2009
      were reviewed. The data were analyzed using SPSS version 11.5. A total of 101
      burn patients were admitted during the study period. The burn patients were aged
      between 4 months and 80 years with a mean age of 32.11 (+/- 3.46) years. The
      overall male to female ratio was 0.83:1. Majority of the patients were Hindus and
      were married. Flame burns were the most common etiology for sustaining burns
      (82.2%). Most of the burn injuries were sustained at home (n = 81, 80.2%), and
      the manner was designated as accidental in 79.2% of the cases. The TBSA
      involvement in burns ranged from 5 to 100% and the mean TBSA was found to be 45.8
      +/- 24.7%. A higher TBSA involvement is associated with an increased risk of
      mortality and this association between TBSA and mortality was found to be
      statistically significant (P < .05). Mortality rate in our study was 40.9%.
      Septicemia (n = 24, 63.2%) was the most common cause of death followed by shock
      (n = 12, 31.6%). Higher mortality is found to be associated with female sex,
      suicides, and flame burns. This study identifies the epidemiological and clinical
      features associated with burn injuries in coastal South India. Majority of the
      burn victims in our study were married females of younger age group. Although the
      manner of sustaining burns was mostly accidental, females were proportionately
      more commonly the victims of suicides and homicides than males. Injuries and
      deaths due to burns are preventable, provided a community-specific preventive
      program is implemented with a strong educational component.

PMID- 22964551
TI  - Enhanced utilization of the "Burn Care Resources in North America" directory.

PMID- 22964552
TI  - Reducing neonatal mortality in Jhagadia Block, Gujarat: we need to go beyond
      promoting hospital deliveries.
AB  - BACKGROUND AND METHODS: We examined data from a cohort of births that occurred in
      the period 2004-08 in the SEWA-Rural project area, covering a population of
      ~175000, in Gujarat, India, to assess the trends and risk factors for neonatal
      mortality. RESULTS: In this population living in 168 villages, there has been a
      significant declining trend in infant and neonatal mortality, more marked in the
      tribal population, in whom this paralleled a rise in the proportion of women
      delivering in hospitals. The more important risk factors for neonatal mortality
      risk to emerge from multivariate analysis are low birth weight, prematurity,
      young age of mother, older mother and high birth order. CONCLUSION: Although
      community based interventions along with promotion of hospital birth has an
      impact in reducing neonatal deaths in this community, sustaining this momentum
      may demand more long-term policy interventions to promote better living standards
      and better reproductive health.

PMID- 22964553
TI  - Fecal incontinence in the elderly: FAQ.
AB  - Fecal incontinence (FI) is a common gastrointestinal (GI) complaint in patients
      aged 65 years and older. This evidence-based review article discusses the
      epidemiology, pathophysiology, evaluation, and management of FI in the geriatric
      population. We emphasize aging-related changes leading to and impacting
      evaluation and treatment of this symptom while incorporating the core geriatric
      principles of functional status and management aligned with patient preference
      and goals of care.

PMID- 22964554
TI  - Diagnostic yield of capsule endoscopy in refractory celiac disease.
AB  - OBJECTIVES: Capsule endoscopy (CE) allows for the assessment of the small bowel
      in numerous intestinal diseases, including celiac disease (CD). The main
      advantage of CE is the complete visualization of the intestinal mucosal surface.
      The objective of this study was to investigate whether CE can predict the
      severity of CD and detect complications. METHODS: We retrospectively studied the
      medical files of 9 patients with symptomatic CD, 11 patients with refractory
      celiac disease type I (RCDI) and 18 patients with refractory celiac disease type
      II (RCDII), and 45 patients without CD who were investigated both CE and upper
      endoscopy or enteroscopy. The type of CD was diagnosed on the basis of a
      centralized histological review, flow cytometry analysis of intraepithelial
      lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex
      polymerase chain reaction. RESULTS: A total of 47 CEs (10, 11, and 26 CEs in the
      symptomatic CD, RCDI, and RCDII groups, respectively) from the 38 celiac patients
      and 47 CEs from the 45 nonceliac patients were retrospectively reviewed. Villous
      atrophy, numerous, or distally located ulcers were more frequent in celiac
      patients than in controls. Among celiac patients, CE was of acceptable quality in
      96% of cases and was complete in 62% of cases. The concordance of CE with
      histology for villous atrophy was better than that of optic endoscopy (kappa
      coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on CE was
      associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). Three
      cases of overt lymphoma were detected by CE during the follow-up. CONCLUSIONS: CE
      findings have a satisfactory concordance with histology and nutritional status in
      patients with symptomatic or refractory CD. Moreover, CE may predict the type of
      RCD and allows for the early detection of overt lymphoma.

PMID- 22964555
TI  - Purification and identification of cell surface antigens using lamprey monoclonal
      antibodies.
AB  - Variable lymphocyte receptor (VLR) B antibodies of the evolutionary distant sea
      lamprey are structurally distinct from conventional mammalian antibodies. The
      different protein architecture and large evolutionary distance of jawless
      vertebrates suggest that VLR antibodies may represent promising tools for
      biomarker discovery. Here we report the generation of panels of monoclonal VLR
      antibodies from lamprey larvae immunized with human T cells and the use of a
      recombinant monoclonal VLR antibody for antigen purification and mass
      spectrometric identification. We demonstrate that despite predicted low affinity
      of individual VLR antigen binding units to the antigen, the high avidity
      resulting from decameric assembly of secreted VLR antibodies allows for efficient
      antigen capture and subsequent identification by mass spectometry. We show that
      VLR antibodies detect their antigens with high specificity and can be used in
      various standard laboratory application techniques. The lamprey antibodies are
      novel reagents that can complement conventional monoclonal antibodies in multiple
      scientific research disciplines.

PMID- 22964557
TI  - Making America more competitive: a paradigm shift in drug and device development.

PMID- 22964556
TI  - A simple technique to enhance the humoral immune response to intracellular
      protein antigens in genetic immunizations.
AB  - A simple technique to enhance the humoral immune response to intracellular
      protein antigens in genetic immunizations is demonstrated in mice. In this
      approach, the intracellular protein is intentionally secreted from expressing
      cells as a chimeric protein, comprising an N-terminal secreted protein fused to
      the intracellular protein antigen. Using the Leishmania chagasi Ldccys1 cysteine
      protease (411CP) as an example of an intracellular protein antigen and both human
      and murine granulocyte colony stimulating factor (GMCSF) as examples of N
      terminal secretion competent fusion partners in chimeric proteins, a humoral
      response in plasmid DNA immunized mice could only be detected by Western blotting
      when the expressed 411CP was secreted.

PMID- 22964558
TI  - Perceived or actual barriers to warfarin use in atrial fibrillation based on
      electronic medical records.
AB  - Compared with usual practice, clinical trials often exclude patients with
      relative contraindications. A study of real-world warfarin use could help inform
      trials of new medications that could potentially replace warfarin. The objective
      of this study was to describe potential barriers to warfarin use among patients
      with atrial fibrillation. This was a retrospective study of electronic medical
      records (1998-2007) from an inner-city public hospital and affiliated primary
      care clinics and included adults aged 18 years or more with atrial fibrillation.
      Exclusions included mitral or aortic valve replacement, hyperthyroidism, or no
      clinical encounter within 1 year after first diagnosis. Warfarin exposure was
      defined by electronic pharmacy or physician order data or, in a second
      definition, international normalized ratio > 1.3. A history of potential barriers
      to warfarin was defined by International Classification of Diagnoses, 9th
      revision codes or electronic medical record "dictionary" terms. Among 3329
      patients, CHADS2 scores were 0 (17%), 1 (26%), 2-6 (57%). Among 1276 patients
      with CHADS2 scores >0 who were prescribed warfarin, rates of potential barriers
      to warfarin were gastrointestinal or genitourinary hemorrhage (20%), alcohol
      abuse (16%), renal insufficiency (15%), predisposition to falls (8%),
      cirrhosis/hepatitis (5%), intracranial hemorrhage (1%), other hemorrhage (6%),
      and age 75 years or more (23%). Among 1475 patients with CHADS2 scores >0 who
      were not prescribed warfarin, these rates differed by not >3% except for
      predisposition to falls (16%) and age 75 years or more (43%). In real-world
      practice, many patients given warfarin have contraindications that would exclude
      them from clinical trials, and many patients apparently eligible for warfarin do
      not receive it.

PMID- 22964559
TI  - Herbal medicine development:  a plea for a rigorous scientific foundation.
AB  - Science, including rigorous basic scientific research and rigorous clinical
      research, must underlie both the development and the clinical use of herbal
      medicines. Yet almost none of the hundreds or thousands of articles that are
      published each year on some aspect of herbal medicines, adheres to 3 simple but
      profound scientific principles must underlie all of herbal drug development or
      clinical use. Three fundamental principles that should underlie everyone's
      thinking about the development and/or clinical use of any herbal medicine. (1)
      There must be standardization and regulation (rigorously enforced) of the product
      being studied or being used clinically. (2) There must be scientific proof of a
      beneficial clinical effect for something of value to the patient and established
      by rigorous clinical research. (3) There must be scientific proof of safety
      (acceptable toxicity) for the patient and established by rigorous clinical
      research. These fundamental principles of science have ramifications for both the
      scientist and the clinician. It is critically important that both the
      investigator and the prescriber know exactly what is in the studied or
      recommended product and how effective and toxic it is. We will find new and
      useful drugs from natural sources. However, we will have to learn how to study
      herbal medicines rigorously, and we will have to try to convince the believers in
      herbal medicines of the wisdom and even the necessity of a rigorous scientific
      approach to herbal medicine development. Both biomedical science and practicing
      physicians must enthusiastically accept the responsibility for searching for
      truth in the discovery and development of new herbal medicines, in the truthful
      teaching about herbal medicines from a scientific perspective, and in the
      scientifically proven clinical use of herbal medicines.

PMID- 22964560
TI  - Utility of early high dose statins in acute coronary syndrome.
AB  - In accordance with the recommendations of the American College of
      Cardiology/American Heart Association Joint Task Force, 3-hydroxy-3
      methylglutaryl-coenzyme A reductase inhibitors (statins) are prescribed before
      hospital discharge after an episode of acute coronary syndrome. Yet, optimal
      timing and dosage have not been agreed upon. Recent evidence suggests a
      pleiotropic mechanism of action including vasoprotective, anti-inflammatory, and
      antiarrhythmic properties that imply an immediate role for statin medications.
      Our review suggests that early (<24 hours) high dose (80 mg of atorvastatin)
      statins may significantly reduce adverse cardiovascular outcomes and may improve
      long-term mortality.

PMID- 22964561
TI  - Effectiveness and cost-effectiveness of dialectical behaviour therapy for self
      harming patients with personality disorder: a pragmatic randomised controlled
      trial.
AB  - BACKGROUND: A primary goal of dialectical behaviour therapy (DBT) is to reduce
      self-harm, but findings from empirical studies are inconclusive. The aim of this
      study was to assess the effectiveness and cost-effectiveness of DBT in reducing
      self-harm in patients with personality disorder. METHODS: Participants with a
      personality disorder and at least 5 days of self-harm in the previous year were
      randomised to receive 12 months of either DBT or treatment as usual (TAU). The
      primary outcome was the frequency of days with self-harm; secondary outcomes
      included borderline personality disorder symptoms, general psychiatric symptoms,
      subjective quality of life, and costs of care. RESULTS: Forty patients each were
      randomised to DBT and TAU. In an intention-to-treat analysis, there was a
      statistically significant treatment by time interaction for self-harm (incidence
      rate ratio 0.91, 95% CI 0.89-0.92, p < 0.001). For every 2 months spent in DBT,
      the risk of self-harm decreased by 9% relative to TAU. There was no evidence of
      differences on any secondary outcomes. The economic analysis revealed a total
      cost of a mean of 5,685 GBP (6,786 EUR) in DBT compared to a mean of 3,754 GBP
      (4,481 EUR) in TAU, but the difference was not significant (95% CI -603 to 4,599
      GBP). Forty-eight per cent of patients completed DBT. They had a greater
      reduction in self-harm compared to dropouts (incidence rate ratio 0.78, 95% CI
      0.76-0.80, p < 0.001). CONCLUSIONS: DBT can be effective in reducing self-harm in
      patients with personality disorder, possibly incurring higher total treatment
      costs. The effect is stronger in those who complete treatment. Future research
      should explore how to improve treatment adherence.

PMID- 22964562
TI  - Impact of estrogen replacement throughout childhood on growth, pituitary-gonadal
      axis and bone in a 46,XX patient with CYP19A1 deficiency.
AB  - BACKGROUND: The adequate replacement dose of estrogens during infancy and
      childhood is still not known in girls. Aromatase deficiency offers an excellent
      model to study how much estrogens are needed during infancy, childhood and
      adulthood. OBJECTIVES: We studied the impact of oral 17beta-estradiol treatment,
      on longitudinal growth, bone age maturation, pituitary gonadotropin feedback,
      multicystic ovaries and bone mass in the long-term follow-up of a girl compound
      heterozygote for two point mutations of the CYP19A1 gene. RESULTS: Low doses of
      17beta-estradiol were needed to achieve normal height velocity and adequate bone
      age maturation from early childhood on. Serum estradiol levels needed for breast
      development and for the appearance of an endometrial reflex were not sufficient
      to achieve physiological gonadotropin levels. Without 17beta-estradiol treatment
      the ovaries of the patient showed a multicystic appearance, which reversed on
      17beta-estradiol replacement. Bone mass was within normal ranges during the whole
      follow-up period. CONCLUSION: In summary, we have shown that estradiol is needed
      not only in puberty but also in childhood for normal growth, bone maturation and
      achievement of normal bone mass. Particularly, this observation underscores the
      importance of early low-dose estrogen replacement also in other estrogen
      deficient conditions as for instance in Turner's syndrome.

PMID- 22964563
TI  - Chapter 1 UK RRT incidence in 2010: national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients
      starting renal replacement therapy (RRT) in the UK in 2010 and the incidence
      rates for RRT in Primary Care Trusts and Health Boards (PCT/HBs) in the UK.
      METHODS: The basic demographics and clinical characteristics are reported on
      patients starting RRT from all UK renal centres. Presentation time, defined as
      time between first being seen by a nephrologist and start of RRT, was also
      studied. Age and gender standardised ratios for incidence rates in PCT/HBs were
      also calculated. RESULTS: In 2010, the incidence rates in the UK and England were
      similar to 2009 at 107 per million population (pmp). The incidence rate fell in
      Scotland (from 104 pmp to 95 pmp), increased in Northern Ireland (from 88 pmp to
      101 pmp) and Wales (from 120 pmp to 128 pmp). There were wide variations between
      PCT/HBs in standardised incidence ratios. The median age of all incident patients
      was 64.9 years (IQR 51.0, 75.2). For transplant centres this was 63.1 years (IQR
      49.7, 74.2) and for non-transplanting centres 66.5 years (IQR 52.9, 76.0). The
      median age for non-Whites was 57.1 years. Diabetic renal disease remained the
      single most common cause of renal failure (24%). By 90 days, 68.3% of patients
      were on haemodialysis, 18.1% on peritoneal dialysis, 7.7% had had a transplant
      and 5.9% had died or stopped treatment. The mean eGFR at the start of RRT was 8.7
      ml/ min/1.73 m(2) which was similar to the previous three years. Late
      presentation (<90 days) fell from 28.2% in 2005 to 20.6% in 2010. There was no
      relationship between social deprivation and presentation pattern. CONCLUSIONS:
      Incidence rates have plateaued in England over the last five years. They have
      fallen in Scotland and fallen and then risen again in Northern Ireland and Wales.
      Wales continued to have the highest incidence rate of the countries making up the
      UK.

PMID- 22964564
TI  - Chapter 6 Survival and causes of death of UK adult patients on renal replacement
      therapy in 2010: national and centre-specific analyses.
AB  - INTRODUCTION: These analyses examine a) survival from the start of renal
      replacement therapy (RRT), based on the total incident UK RRT population reported
      to the UK Renal Registry, including the 18% who started on PD and the 7% who
      received a pre-emptive transplant and b) survival of prevalent patients. Changes
      in survival between 1997 and 2009 are also reported. METHODS: Survival of
      incident patients (starting RRT during 2009) was calculated both from the start
      of RRT and from 90 days after starting RRT, both with and without censoring at
      transplantation. Survival of prevalent dialysis patients was calculated to
      exclude patients once they were transplanted. Both Kaplan-Meier and Cox adjusted
      models were used to calculate survival. Causes of death were analysed for both
      groups. Relative risk of death was calculated compared with the general UK
      population. RESULTS: The 2009 unadjusted 1 year after 90 day survival for
      patients starting RRT was 86.6% (87.3% in 2008). In incident patients aged 18-64,
      the unadjusted 1 year survival had increased from 86.0% in 1997 to 91.3% in 2009.
      In incident patients aged >= 65, unadjusted 1 year survival had improved from
      64.1% to 76.2%. There were no survival differences between genders. The relative
      risk of death compared to the general population decreased from 25 times at age
      30-34 to 2.7 times at age 85+. Cause of death data completeness has improved 18%
      since last year. Cardiac disease is the most common cause of death in prevalent
      dialysis patients and malignancy most frequent in prevalent transplant patients.
      CONCLUSIONS: Survival of patients starting RRT has improved for all ages since
      1997. The frequency of cardiac disease as the cause of death has decreased since
      1997.

PMID- 22964565
TI  - Chapter 7 Adequacy of haemodialysis in UK adult patients in 2010: national and
      centre-specific analyses.
AB  - BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by
      the delivered dose of dialysis. The UK Renal Association (RA) publishes clinical
      practice guidelines which include recommendations for dialysis dose. The urea
      reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To
      determine the extent to which patients received the recommended dose of HD in the
      UK. METHODS: All seventy-two UK renal centres submitted data to the UK Renal
      Registry (UKRR). Two groups of patients were included in the analyses: the
      prevalent patient population on 31st December 2010 and the incident patient
      population for 2010. Centres returning data on <50% of their patient population
      or centres with <20 patients were excluded from centre-specific comparisons.
      RESULTS: Data regarding URR were available from 64 renal centres in the UK. Forty
      nine centres provided URR data on more than 90% of prevalent patients. The
      proportion of patients in the UK who met the UK clinical practice guideline for
      URR (>65%) increased from 56% in 1998 to 86% in 2010. There was persistent
      variation observed between centres, with 19 centres attaining the RA clinical
      practice guideline in >90% of patients and 39 centres attaining the guideline in
      70-90%. The overall proportion of prevalent patients with a URR >65% has
      continued to improve over time. CONCLUSIONS: The delivered dose of HD for
      patients with established renal failure has increased over the last decade.
      Whilst the majority of UK patients achieved the target URR there was considerable
      variation between centres in the percentage of patients achieving the guideline.

PMID- 22964566
TI  - Chapter 8 Haemoglobin, ferritin and erythropoietin amongst UK adult dialysis
      patients in 2010: national and centre-specific analyses.
AB  - BACKGROUND: The UK Renal Association (RA) and National Institute for Health and
      Clinical Excellence (NICE) have published clinical practice guidelines which
      include recommendations for management of anaemia in established renal failure.
      AIM: To determine the extent to which the guidelines for anaemia management are
      met in the UK. METHODS: Quarterly data were obtained regarding haemoglobin (Hb)
      and factors that influence Hb from renal centres in England, Wales, Northern
      Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent
      renal replacement therapy (RRT) cohorts for 2010. RESULTS: In the UK, in 2010
      53.6% of patients commenced dialysis therapy with Hb >= 10.0 g/dl (median Hb 10.1
      g/dl). The median Hb of haemodialysis (HD) patients was 11.5 g/dl with an
      interquartile range (IQR) of 10.5-12.3 g/dl. Of HD patients 84.6% had Hb >= 10.0
      g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.6 g/dl
      (IQR 10.6-12.5 g/dl). Of UK PD patients, 87.2% had Hb >= 10.0 g/dl. The median
      ferritin in HD patients in EWNI was 444 ug/L (IQR 299-635) and 96% of HD patients
      had a ferritin >= 100 ug/L. The median ferritin in PD patients was 264 ug/L (IQR
      148-426) with 86% of PD patients having a ferritin >= 100 ug/L. In EWNI the mean
      Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients
      (9,020 vs. 6,202 IU/week). CONCLUSIONS: Of prevalent HD patients, 52.7% had Hb >=
      10 and <= 12 g/dl. Of prevalent PD patients, 54.3% had Hb 10.5-12.5 g/dl.

PMID- 22964567
TI  - Chapter 9 Biochemical variables amongst UK adult dialysis patients in 2010:
      national and centre-specific analyses.
AB  - INTRODUCTION: The UK Renal Association clinical practice guidelines include
      clinical performance measures for biochemical variables in dialysis patients. The
      UK Renal Registry (UKRR) annually audits dialysis centre performance against
      these measures as part of its role in promoting continuous quality improvement.
      METHODS: Cross sectional performance analyses were undertaken to compare dialysis
      centre achievement of clinical audit measures for prevalent haemodialysis (HD)
      and peritoneal dialysis (PD) cohorts in 2010. The biochemical variables studied
      were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total
      cholesterol. In addition longitudinal analyses were performed (2000-2010) to show
      changes in achievement of clinical performance measures over time. RESULTS: Fifty
      six percent of HD and 69% of PD patients achieved a phosphate within the range
      recommended by the RA clinical practice guidelines. Seventy-five percent of HD
      and 76% of PD patients had adjusted calcium between 2.2-2.5 mmol/L. Twenty-eight
      percent of HD and 31% of PD patients had parathyroid hormone between 16- 32
      pmol/L. Sixty percent of HD and 80% of PD patients achieved the audit measure for
      bicarbonate. There was significant inter-centre variation for all variables
      studied. CONCLUSIONS: The UKRR consistently demonstrates significant inter-centre
      variation in achievement of biochemical clinical audit measures. Understanding
      the causes of this variation is an important part of improving the care of
      dialysis patients in the UK.

PMID- 22964568
TI  - Chapter 10 Blood pressure profile of prevalent patients receiving renal
      replacement therapy in England, Wales and Northern Ireland in 2010: national and
      centre-specific analyses.
AB  - BACKGROUND: The UK Renal Registry (UKRR) assesses blood pressure (BP) control
      annually for patients receiving renal replacement therapy (RRT) at renal centres
      in England, Wales and Northern Ireland. METHODS: Patients receiving RRT on 31st
      December 2010 with a BP reading in either the fourth or third quarter of 2010
      were included. Summary statistics were calculated for each renal centre and
      country. RESULTS: Data completeness for BP measurements submitted to the UKRR for
      all modalities were little changed from previous years: it was better for HD
      patients (64% for pre-HD measurements) than for PD patients (44%) or transplant
      recipients (36%). In 2010, the median pre-and post-HD SBP were 140 mmHg and 128
      mmHg respectively. The median SBP of patients on PD was 138 mmHg. Transplant
      recipients had a median SBP of 134 mmHg. Median DBP were 71 mmHg (pre-HD), 67
      mmHg (post-HD), 80 mmHg (PD ) and 79 mmHg (transplant). Only 25.6% of PD patients
      achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg.
      Amongst transplant patients, 27.7% achieved the Renal Association guideline of
      SBP <130 mmHg and DBP <80 mmHg. CONCLUSION: In 2010 there continued to be
      significant variation in the achievement of BP standards between UK renal
      centres.

PMID- 22964569
TI  - Chapter 11 Clinical, haematological and biochemical parameters in patients
      receiving renal replacement therapy in paediatric centres in the UK in 2010:
      national and centre-specific analyses.
AB  - BACKGROUND: The British Association for Paediatric Nephrology Registry was
      established to analyse data related to renal replacement therapy (RRT) for
      children. The registry receives data from the 13 paediatric nephrology centres in
      the UK. AIM: To provide centre specific data so that individual centres can
      reflect on the contribution that their data makes to the national picture and to
      determine the extent to which their patient parameters meet nationally agreed
      audit standards for the management of children with established renal failure.
      METHOD: Data returns have been a mixture of electronic and paper returns. Data
      were analysed to calculate summary statistics and where applicable the percentage
      achieving an audit standard. The standards used were those set out by the Renal
      Association and the National Institute for Health and Clinical Excellence.
      RESULTS: Anthropometric data confirmed that children receiving RRT are short
      compared to healthy peers. Amongst patients with a height z-score of <2SD between
      2000 and 2010, 27% were receiving growth hormone if they were on dialysis
      compared to 10% if they had a functioning transplant. Blood pressure was higher
      in children receiving RRT than in healthy children with wide inter-centre
      variation. The percentage of patients achieving the treatment standards for
      haemoglobin and ferritin has gradually increased over the last decade, more
      noticeably in dialysis patients. Analysis by age showed that the proportion of
      children with a haemoglobin below the standard was greatest for the under 5 years
      age group irrespective of RRT modality. The control of renal bone disease
      remained challenging. CONCLUSIONS: Optimizing growth in children on RRT remains
      challenging and the control of bone biochemistry in children on dialysis is
      imperfect. However there is some room for optimism as this year's data shows an
      improving trend in the control of anaemia and systolic blood pressure.

PMID- 22964570
TI  - Chapter 12 Epidemiology of Staphylococcus aureus bacteraemia amongst patients
      receiving dialysis for established renal failure in England in 2009 to 2011: a
      joint report from the Health Protection Agency and the UK Renal Registry.
AB  - INTRODUCTION: Infection remains one of the leading causes of death in patients
      with end-stage renal failure (ESRF) receiving dialysis. Since April 2007, all
      centres providing renal replacement therapy in England have been required to
      provide additional data on patients with Methicillin Resistant Staphylococcus
      Aureus (MRSA) infection. From January 2011 this has also been required for
      patients with Methicillin Sensitive Staphylococcus Aureus (MSSA). MRSA data for
      2009-2011 and the first 6 months of MSSA data are reported. METHODS: Potential
      bacteraemia were identified by the Health Protection Agency based on clinical
      details provided and the clinical setting. The records were 'shared' with the
      parent renal centre who then complete the additional data on the HCAI-DCS
      website. Centres were also contacted by phone and email as a further validation
      step. RESULTS: From April 2009-2010 there were 77 confirmed episodes of MRSA
      bacteraemia at a median rate of 0.25 per 100 prevalent dialysis patients. This
      number decreased to 61 episodes between April 2010-2011 at a median rate of 0 per
      100 prevalent dialysis patients. Overall there has been an 82% reduction in
      absolute episodes since the first year of mandatory reporting in 2007. The
      incidence of bacteraemia in patients with a central venous catheter was
      approximately six fold higher than in those with an AV fistula. From 1st January
      to 30th June 2011 there were 160 episodes of MSSA bacteraemia with a rate of 1.06
      episodes per 100 dialysis patients, again the risk was six fold higher in
      patients with a CVC. CONCLUSIONS: Overall rates of MRSA bacteraemia in dialysis
      patients continued to fall although there remained variation between renal
      centres. Initial data from the early days of MSSA reporting suggested high rates
      of infection and an even greater variation between renal centres. This requires
      confirmation from future data collection.

PMID- 22964571
TI  - Chapter 13 The linkage of incident renal replacement therapy patients in England
      (2002-2006) to hospital episodes and national mortality data: improved demography
      and hospitalisation data in patients undergoing renal replacement therapy.
AB  - INTRODUCTION: Missing data has hampered the comprehensive and inclusive reporting
      of adjusted outcomes for patients on renal replacement therapy (RRT) captured by
      the UK Renal Registry (UKRR). Furthermore the information collected by the UKRR
      does not currently include morbidity after starting RRT, details on hospital
      admission rates or location of death. Linking datasets offers the opportunity to
      enhance existing data and describe new measures of centre performance. METHODS:
      21,633 incident patients, starting RRT between 2002 and 2006, were linked to all
      hospital care recorded by the Hospital Episode Statistics (HES) database and
      Office of National Statistics (ONS) mortality data using a secure anonymised
      service. Comorbidity prior to admission was determined from ICD10 coded HES
      admission diagnoses before the start of RRT, along with missing data on ethnicity
      and socioeconomic status. Location of death was determined by comparing the ONS
      and UKRR date of death to concurrent hospitalisations from HES. RESULTS: 290,443
      admissions, 2.2 million haemodialysis attendances, 1.5 million outpatient
      attendances and 11,546 ONS deaths were returned for this cohort. Coding depth
      improved over time and varied between centres. Following linkage 21,271 patients
      were suitable for analysis, with improvements in ethnicity completeness (75.5% to
      98.9%) and socioeconomic status (72.0% to 98.6%). Comorbidity improved
      substantially from 53.7% to 98.1% with 93% concordance in those with UKRR data.
      Mean comorbid scores between centres was similar (0.73-1.14) but variation in the
      proportion of admissions under nephrology in the first 12 months and the location
      of death between centres was noted, suggesting differing policies, practices and
      coding methods. CONCLUSIONS: Linking routine healthcare datasets with a national
      registry has dramatically reduced missing data and enables reporting of
      additional comprehensively adjusted measures of performance that allow more
      robust comparisons between centres. Hospitalisation frequency and associated
      mortality can be described in much greater detail. Linking routine datasets to
      national audits and registries represents an achievable, cost-effective and
      illuminating new way to evaluate services such as renal replacement therapy in
      the English NHS.

PMID- 22964572
TI  - Chapter 14 Comparative audit of peritoneal dialysis catheter placement in
      England, Northern Ireland and Wales in 2011: a summary of progress to July 2012.
AB  - BACKGROUND: The central paradigm of effective peritoneal dialysis (PD) is an
      appropriate standard of PD catheter function. AIM: The ultimate aim of the
      project is to develop an effective national PD access audit which will identify
      what represents an 'appropriate standard' of PD catheter function. METHODS: A
      2009 Renal Association working party recommended that the UK Renal Registry
      should collect centre specific information on various PD access outcome measures
      including catheter functionality and post-insertion complications. RESULTS: The
      first PD access audit covering England, Northern Ireland and Wales was conducted
      during April to June 2012 looking at incident dialysis patients in 2011. Forty
      three data collection spreadsheets were returned from a total of 63 centres
      describing 863 PD catheter placements of which 225 had a missing date of
      insertion. Results will be published on the UK Renal Registry website as soon as
      they are available. DISCUSSION: There is clearly much to be learned as the
      project is progressed, including minimising data ambiguities and trying to
      maximise data completeness (for example it is possible that a patient with a
      catheter that never worked and never had PD may be overlooked in this audit).
      However, a comparative PD catheter audit has the potential to provide valuable
      information on an important patient related outcome measure and lead to an
      improvement in patient experience.

PMID- 22964573
TI  - Chapter 2 UK RRT prevalence in 2010: national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients on
      renal replacement therapy (RRT) in the UK in 2010. METHODS: Data were
      electronically collected from all 72 renal centres within the UK. Cross-sectional
      and longitudinal analyses were performed to describe the demographics of
      prevalent RRT patients in 2010 at centre and national level. Age and gender
      standardised ratios for prevalence rates per million population per year were
      calculated. RESULTS: There were 50,965 adult patients receiving RRT in the UK on
      31st December 2010. The UK prevalence of RRT (including paediatric patients) was
      832 pmp. This represented an annual increase in prevalent numbers of
      approximately 4% although there was significant variation between centres and
      regions. From 2009 to 2010 there was a 1.5% increase in the number of patients on
      haemodialysis (HD), a 3.2% fall in peritoneal dialysis (PD) patients and a 5.4%
      increase in patients with a functioning transplant. The number of patients
      receiving home HD has increased 23% since 2009. Median RRT vintage was 5.6 years.
      The median age was 57.9 years (HD 66.3 years, PD 61.7 years and transplant 51.2
      years) compared to 55 years in 2000. Prevalence rates in males exceeded those in
      females. The most common identifiable renal diagnosis was biopsyproven
      glomerulonephritis (16.0%), followed by diabetes (14.9%). Transplantation was the
      most common treatment modality (48%), HD in 44% and PD 8%. CONCLUSIONS: The HD
      and transplant population continued to expand whilst the PD population
      contracted. There were national, regional and dialysis centre level variations in
      prevalence rates. Prevalent patients were on average 4 years older than 10 years
      ago. This has implications for service planning and ensuring equity of care for
      RRT patients.

PMID- 22964574
TI  - Chapter 3 Demographic and biochemistry profile of kidney transplant recipients in
      the UK in 2010: national and centre-specific analyses.
AB  - INTRODUCTION: National transplant registries routinely focus on centre-specific
      patient and graft survival rates following renal transplantation. However other
      outcomes such as graft function (as measured by eGFR), haemoglobin and blood
      pressure are also important quality of care indicators. METHODS: Renal transplant
      activity, incident graft survival data and donor information were obtained from
      NHS Blood and Transplant. Laboratory and clinical variables and prevalent
      survival data were obtained from the UK Renal Registry. Data were analysed
      separately for prevalent and one year post-transplant patients. RESULTS: The
      numbers of live and deceased kidney donors increased in 2010. The death-censored
      graft failure rate fell slightly to 2.4% and the transplant patient death rates
      remained stable at 2.5 per 100 patient years. There was centre variation in
      outcomes including eGFR and haemoglobin in prevalent and 1 year post-transplant
      patients. Analysis of prevalent transplants by chronic kidney disease stage
      showed 13.7% with an eGFR <30 ml/min/1.73 m(2) and 1.5% with an eGFR <15
      ml/min/1.73 m(2). Of those with CKD stage 5 T, 36.1% had haemoglobin
      concentrations <10.5 g/dl, 22.9% phosphate concentrations >= 1.8 mmol/L and 6.2%
      adjusted calcium concentrations >= 2.6 mmol/L. Malignancy (23%) and infection
      (22%) remained the commonest two causes of death in prevalent transplant
      patients. CONCLUSION: Significant variations in clinical outcomes (unadjusted for
      patient-specific variables) amongst kidney transplant recipients continued to
      exist in the UK and may reflect differences in healthcare delivery between renal
      centres.

PMID- 22964575
TI  - Chapter 4 Comorbidities and current smoking status amongst patients starting
      renal replacement therapy in England, Wales and Northern Ireland from 2009 to
      2010.
AB  - INTRODUCTION: Comorbidities are an important determinant of survival for patients
      requiring renal replacement therapy (RRT) and influence other care processes such
      as dialysis access formation and transplant wait-listing. The prevalence of
      comorbidities in incident RRT patients changes with age and varies between ethnic
      groups. This study describes these associations and the independent effect of
      comorbidities on outcomes. METHODS: Incident patients reported to the UK Renal
      Registry (UKRR) with comorbidity data in 2009 and 2010 (n = 6,130) were included
      in analyses exploring the association of comorbidities with patient demographics,
      treatment modality, haemoglobin and renal function at start of RRT. For analyses
      examining association between comorbidities and survival, adult patients starting
      RRT between 2005 and 2010 in centres reporting to the UKRR with comorbidity data
      (n = 17,184) were included. The relationship between comorbidities and mortality
      at 90 days and one year after 90 days from start of RRT were explored using Cox
      regression. RESULTS: Completeness of comorbidity data was 49.1% in 2010 compared
      with 48.9% in 2005. Of patients with data, 55.4% had one or more comorbidities.
      Diabetes mellitus and ischaemic heart disease were the most common conditions,
      observed in 33.3% and 21.1% of patients respectively. 13.2% of incident RRT
      patients in the 2-year period were recorded as current smokers. The prevalence of
      comorbidity increased with increasing age across all ethnic groups. In
      multivariable survival analysis, malignancy and the presence of
      ischaemic/neuropathic ulcers were strong independent predictors of poor survival
      at 1 year after 90 days from the start of RRT in patients <65 years. CONCLUSION:
      Differences in prevalence rates of comorbid illnesses in incident RRT patients
      may reflect variation in access to health care or competing risk prior to
      commencing treatment. The generalisability of these analyses continues to be
      limited by poor data completeness.

PMID- 22964576
TI  - Chapter 5 Demography of the UK paediatric renal replacement therapy population in
      2010.
AB  - AIMS: To describe the demographics of the paediatric RRT population under the age
      of 16 years in the UK and to analyse changes in demography with time. METHODS:
      Data were collected from all 13 paediatric renal centres within the UK. A series
      of cross-sectional and longitudinal analyses were performed to describe the
      demographics of prevalent paediatric RRT patients. RESULTS: A total of 870
      children and young people under 18 with ERF were receiving treatment at
      paediatric nephrology centres in 2010. At the census date, 76.7% had a
      functioning transplant, 14.3% were receiving peritoneal dialysis (PD) and 9.0%
      were receiving haemodialysis (HD). In patients aged <16 years the prevalence of
      ERF was 59.3 pmarp and the incidence 8.1 pmarp. Analysis of trends over the last
      15 years shows that both incidence and prevalence are increasing with the most
      marked increases in children aged 12-16 years and in ethnic minority groups. A
      third of the patients have one or more reported comorbidities. At transfer to
      adult services, 84.9% of patients had a functioning renal transplant.
      CONCLUSIONS: The data provided in this report show increasing trends over 15
      years in the incidence and prevalence of established renal failure. This is
      important for the planning of the provision of care for children needing renal
      replacement therapy. The inclusion this year of an analysis of the patients
      transferring to adult services may assist in developing care pathways for this
      vulnerable group.

PMID- 22964577
TI  - Poly(ADP-ribosyl)ation is a survival mechanism in cigarette smoke-induced and
      hydrogen peroxide-mediated cell death.
AB  - Cigarette smoking can contribute to the development of many human diseases such
      as cardiovascular disease, lung cancer, asthma, and chronic obstructive pulmonary
      disease. Thousands of compounds are present in cigarette smoke, including a large
      number of reactive oxygen species that can cause DNA damage, leading to the
      activation of poly(ADP-ribose) polymerase (PARP) enzymes. The PAR polymer is
      degraded by poly(ADP-ribose) glycohydrolase (PARG). Here we have investigated the
      effects of cigarette smoke extract (CSE) on A549 human lung epithelial cells. CSE
      induced DNA damage (comet assay), PAR accumulation (immunofluorescence and
      immunoblotting), impaired proliferation (clonogenic survival assay and electric
      cell-substrate impedance sensing measurement), and cell death (MTT reduction,
      propidium iodide uptake, lactate dehydrogenase release). CSE-induced cell death
      was also characterized by mitochondrial depolarization but massive translocation
      of apoptosis-inducing factor could not be observed. To investigate the role of
      PARylation in CSE-induced oxidative stress, PARP-1- and PARG-silenced A549 cells
      were used. Silencing of both PARP-1 and PARG sensitized cells to CSE-induced
      toxicity: PARP-1- and PARG-silenced cell lines exhibited reduced clonogenic
      survival, displayed a delayed repair of DNA breaks, and showed higher levels of
      cytotoxicity. CSE triggered the production of mitochondrial superoxide and
      hydrogen peroxide. Addition of superoxide dismutase increased, whereas catalase
      abolished, CSE-induced PAR formation. In summary, our data show that the
      superoxide-hydrogen peroxide-DNA breakage pathway activates the PAR cycle by PARP
      1 and PARG, which serves as a survival mechanism in CSE-exposed cells. Our data
      also raise the possibility that the PARP-1/PARG status of smokers may be an
      important determinant of the efficiency of DNA repair in their lungs and of their
      susceptibility to CS-induced carcinogenesis.

PMID- 22964578
TI  - High predictability of a sustained virological response (87%) in chronic
      hepatitis C virus genotype 1 infection treatment by combined IL28B genotype
      analysis and gamma-glutamyltransferase/alanine aminotransferase ratio: a
      retrospective single-center study.
AB  - BACKGROUND: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated
      with pegylated interferon-alpha and ribavirin. Predictive factors for treatment
      success are even more important now as direct-acting antiviral agents are
      available. METHODS: Clinical and laboratory parameters were analyzed by uni- and
      multivariate statistical means in 264 patients with HCV-G1 infections with regard
      to treatment outcome. RESULTS: The overall sustained virological response (SVR)
      rate was 44%. Univariate analyses revealed SVRs to be associated with age, high
      alanine aminotransferase (ALT) and low gamma-glutamyltransferase (gamma-GT) serum
      activities, a low pretreatment gamma-GT/ALT ratio, rapid virological response
      (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860
      genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI:
      3.1-16.7, p < 0.001), low pretreatment gamma-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3,
      p < 0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI:
      2.85-8.65, p < 0.001) to be significantly related to treatment outcome. Patients
      with the IL28B rs12979860 CC genotype and a low pretreatment gamma-GT/ALT ratio
      achieved the highest rate of a SVR with the highest predictive values (OR = 26.7,
      95% CI: 10-71.1, p < 0.0001). CONCLUSION: The pretreatment gamma-GT/ALT ratio
      significantly enhances the predictability of the IL28B genotype. Employing this
      combination will help to identify patients who will most likely benefit from an
      interferon-alpha-based combination therapy in a nontriaged ordinary setting.

PMID- 22964579
TI  - Oncogene addiction to c-MYC in myeloma cells.

PMID- 22964580
TI  - Multiple roles of p53-related pathways in somatic cell reprogramming and stem
      cell differentiation.
AB  - The inactivation of p53 functions enhances the efficiency and decreases the
      latency of producing induced pluripotent stem cells (iPSC) in culture. The
      formation of iPSCs in culture starts with a rapid set of cell divisions followed
      by an epigenetic reprogramming of the DNA and chromatin. The mechanisms by which
      the p53 protein inhibits the formation of iPSCs are largely unknown. Using a
      temperature sensitive mutant of the p53 (Trp53) gene, we examined the impact of
      the temporal expression of wild type p53 in preventing stem cell induction from
      somatic cells. We also explored how different p53 mutant alleles affect the
      reprogramming process. We found that little or no p53 activity favors the entire
      process of somatic cell reprogramming. Reactivation of p53 at any time point
      during the reprogramming process not only interrupted the formation of iPSCs, but
      also induced newly formed stem cells to differentiate. Among p53-regulated genes,
      p21 (Cdkn1a), but not Puma (Bbc3) played a partial role in iPSCs formation
      probably by slowing cell division. Activation of p53 functions in iPSCs induced
      senescence and differentiation in stem cell populations. High rate of birth
      defects and increases in DNA methylation at the IGF2-H19 loci in female offspring
      of p53 knockout mice suggested that the absence of p53 may give rise to
      epigenetic instability in a stochastic fashion. Consistently, selected p53
      missense mutations showed differential effects on the stem cell reprogramming
      efficiency in a c-Myc dependent manner. The absence of p53 activity and functions
      also contributed to an enhanced efficiency of iPSC production from cancer cells.
      The production of iPSCs in culture from normal and cancer cells, although
      different from each other in several ways, both responded to the inhibition of
      reprogramming by the p53 protein.

PMID- 22964581
TI  - Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast
      cancer cells.
AB  - Despite the fact that most breast cancer patients have estrogen receptor (ER)
      alpha-positive tumors, up to 50% of the patients are or soon develop resistance
      to endocrine therapy. It is recognized that HER2 activation is one of the major
      mechanisms contributing to endocrine resistance. In this study, we report that
      the ER coactivator MED1 is a novel cross-talk point for the HER2 and ERalpha
      pathways. Tissue microarray analysis of human breast cancers revealed that MED1
      expression positively correlates most strongly with HER2 status of the tumors.
      MED1 was highly phosphorylated, in a HER2-dependent manner, at the site known to
      be critical for its activation. Importantly, RNAi-mediated attenuation of MED1
      sensitized HER2-overexpressing cells to tamoxifen treatment. MED1 and its
      phosphorylated form, but not the corepressors N-CoR and SMRT, were recruited to
      the ERalpha target gene promoter by tamoxifen in HER2-overexpressing cells.
      Significantly, MED1 attenuation or mutation of MED1 phosphorylation sites was
      sufficient to restore the promoter recruitment of N-CoR and SMRT. Notably, we
      found that MED1 is required for the expression of not only traditional E2-ERalpha
      target genes but also the newly described EGF-ERalpha target genes. Our results
      additionally indicated that MED1 is recruited to the HER2 gene and required for
      its expression. Taken together, these findings support a key role for MED1 in
      HER2-mediated tamoxifen resistance and suggest its potential usage as a
      therapeutic target to simultaneously block both ERalpha and HER2 pathways for the
      treatment of this type of endocrine resistant breast cancer.

PMID- 22964582
TI  - miRNA-34 prevents cancer initiation and progression in a therapeutically
      resistant K-ras and p53-induced mouse model of lung adenocarcinoma.
AB  - Lung cancer is the leading cause of cancer deaths worldwide, and current
      therapies fail to treat this disease in the vast majority of cases. The RAS and
      p53 pathways are two of the most frequently altered pathways in lung cancers,
      with such alterations resulting in loss of responsiveness to current therapies
      and decreased patient survival. The microRNA-34 (mir-34) gene family members are
      downstream transcriptional targets of p53, and miR-34 expression is reduced in
      p53 mutant tumors; thus, we hypothesized that treating mutant Kras;p53 tumors
      with miR-34 would represent a powerful new therapeutic to suppress lung
      tumorigenesis. To this end we examined the therapeutically resistant Kras(LSL
      G12D)(/+);Trp53(LSL-R172H)(/+) mouse lung cancer model. We characterized tumor
      progression in these mice following lung-specific transgene activation and found
      tumors as early as 10 weeks postactivation, and severe lung inflammation by 22
      weeks. Tumors harvested from these lungs have elevated levels of oncogenic
      miRNAs, miR-21 and miR-155; are deficient for p53-regulated miRNAs; and have
      heightened expression of miR-34 target genes, such as Met and Bcl-2. In the
      presence of exogenous miR-34, epithelial cells derived from these tumors show
      reduced proliferation and invasion. In vivo treatment with miR-34a prevented
      tumor formation and progression in Kras(LSL-G12D)(/+);Trp53(LSL-R172H)(/+) mice.
      Animals infected with mir-34a-expressing lentivirus at the same time as transgene
      activation had little to no evidence of tumorigenesis, and lentivirus-induced miR
      34a also prevented further progression of preformed tumors. These data support
      the use of miR-34 as a lung tumor-preventative and tumor-static agent.

PMID- 22964583
TI  - Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict
      survival outcomes in breast cancer.
AB  - NRF2 activates several protective genes, such as sulfiredoxin (SRXN1), as a
      response to oxidative and xenobiotic stress. Defects in NRF2 pathway may increase
      cancer susceptibility. In tumor cells, activation of NRF2 may lead to chemo- and
      radioresistance and thus affect patient outcome. Nine single-nucleotide
      polymorphisms on NRF2 gene and eight on SRXN1 were genotyped in 452 patients with
      breast cancer and 370 controls. Protein expression of NRF2 and SRXN1 was studied
      in 373 breast carcinomas by immunohistochemistry. Statistical significance of the
      associations between genotypes, protein expression, clinicopathologic variables,
      and survival was assessed. A high level (>25%) of cytoplasmic NRF2 positivity was
      observed in 237 of 361 (66%) and SRXN1 positivity was observed in 82 of 363 (23%)
      cases. The NRF2 rs6721961 genotype TT was associated with increased risk of
      breast cancer [P = 0.008; OR, 4.656; confidence interval (CI), 1.350-16.063] and
      the T allele was associated with a low extent of NRF2 protein expression (P =
      0.0003; OR, 2.420; CI, 1.491-3.926) and negative SRXN1 expression (P = 0.047; OR,
      1.867; CI = 1.002-3.478). The NRF2 rs2886162 allele A was associated with low
      NRF2 expression (P = 0.011; OR, 1.988; CI, 1.162-3.400) and the AA genotype was
      associated with a worse survival (P = 0.032; HR, 1.687; CI, 1.047-2.748). The
      NRF2 rs1962142 T allele was associated with a low level of cytoplasmic NRF2
      expression (P = 0.036) and negative sulfiredoxin expression (P = 0.042). The NRF2
      rs2706110 AA genotype was associated with an increased risk of breast cancer, and
      the SRXN1 rs6053666 C allele was associated with a decrease in breast cancer risk
      (P = 0.011 and 0.017). NRF2 and SRXN1 genetic polymorphisms are associated with
      breast cancer risk and survival, implicating that mechanisms associated with
      reactive oxygen species and NRF2 pathway are involved in breast cancer initiation
      and progression.

PMID- 22964584
TI  - Basic research: Mouse study shows spermatogenesis inhibitor is effective as a
      reversible male contraceptive.

PMID- 22964585
TI  - Micro/nano-structured CaWO4/Bi2WO6 composite: synthesis, characterization and
      photocatalytic properties for degradation of organic contaminants.
AB  - The micro/nano-structured CaWO(4)/Bi(2)WO(6) composite was successfully
      synthesized by a one-step hydrothermal route without using any templates or
      surfactants. The as-prepared samples were characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), Fourier transform
      infrared (FT-IR) spectroscopy, thermogravimetry-differential scanning calorimetry
      (TG-DSC) and Brunauer-Emmet-Teller (BET) theory. The results indicated that the
      composite has a two-phase composition: CaWO(4) and Bi(2)WO(6). The photocatalytic
      activities of the CaWO(4)/Bi(2)WO(6) composite were evaluated for the degradation
      of Rhodamine B (RhB) dye and 4-nitrophenol (4-NP) in aqueous solution under
      visible-light irradiation (>420 nm), which were 4.5 times and 2.5 times higher
      than that of the pure Bi(2)WO(6), respectively. On the basis of the calculated
      energy band positions, the mechanism of enhanced photocatalytic activity for the
      micro/nano-structured CaWO(4)/Bi(2)WO(6) composite can be attributed to the
      effective separation of electron-hole pairs.

PMID- 22964587
TI  - Reversible electron-induced cis-trans isomerization mediated by intermolecular
      interactions.
AB  - Reversible isomerization processes are rarely found when organic molecular
      switches are adsorbed on metal surfaces. One obstacle is the large energy
      difference of the isomeric forms, since usually the most planar conformer has the
      largest adsorption energy. In the example of an imine derivative, we show a
      strategy for also stabilizing the non-planar isomer by intermolecular bonding to
      its neighbors. Tunneling electrons from the tip of a scanning tunneling
      microscope can then be used to induce reversible switching between the trans and
      cis-like state. Supported by model force-field calculations, we illustrate that
      the most probable cause of the enhanced stability of the three-dimensional cis
      state at specific adsorption sites is the electrostatic interaction with N sites
      of the neighboring molecule.

PMID- 22964588
TI  - An evaluation of disease knowledge in dyads of parents and their adolescent
      children with congenital heart disease.
AB  - BACKGROUND: Congenital heart disease (CGHD) can be considered a chronic disease
      for many patients. To adopt a healthy lifestyle and to avoid complications,
      patients with CGHD and their parents need to have good knowledge of the heart
      defect and its consequences. OBJECTIVE: The aims of this study were to evaluate
      patient and parental knowledge of CGHD and to explore the related factors of
      their respective disease knowledge. METHODS: This study included 116 dyads of
      adolescents with CGHD (43.1% male adolescents; aged 12-18 years) and one of their
      parents (79.3% mothers; median age, 46 years). All participants completed the
      Leuven Knowledge Questionnaire for Congenital Heart Disease, and then we
      calculated a correct rate score to determine the overall disease knowledge of the
      respondents. RESULTS: The correct rate score was 38.8% for adolescents with CGHD
      and 51.4% for parents (t = 7.69; P < .001). The only determinant of knowledge in
      parents was their educational level (standardized estimate = 6.160, P < .001). In
      adolescents, knowledge was determined by age (standardized estimate = 2.242, P =
      .002) and parental knowledge (standardized estimate = 0.311, P < .001).
      CONCLUSIONS: Although parents have significantly greater disease knowledge than
      their children do, the level of knowledge in both parents and adolescents is
      suboptimal. Because parents' knowledge influenced their adolescents' knowledge,
      educational interventions should target both adolescent patients and parents.
      Transition programs can play a pivotal role in this respect.

PMID- 22964590
TI  - Rescuing the neonatal brain from hypoxic injury with autologous cord blood.
AB  - Brain injury resulting from perinatal hypoxic-ischemic encephalopathy (HIE) is a
      major cause of acute mortality in infants and chronic neurologic disability in
      surviving children. Recent multicenter clinical trials demonstrated the
      effectiveness of hypothermia initiated within the first 6 postnatal hours to
      reduce the risk of death or major neurological disabilities among neonates with
      HIE. However, in these trials, approximately 40% of cooled infants died or
      survived with significant impairments. Therefore, adjunct therapies are required
      to improve the outcome in neonates with HIE. Cord blood (CB) is a rich source of
      stem cells. Administration of human CB cells in animal models of HIE has
      generally resulted in improved outcomes and multiple mechanisms have been
      suggested including anti-inflammation, release of neurotrophic factors and
      stimulation of endogenous neurogenesis. Investigators at Duke are conducting
      studies of autologous CB infusion in neonates with HIE and in children with
      cerebral palsy. These pilot studies indicate no added risk from the regimens
      used, but results of ongoing placebo-controlled trials are needed to assess
      efficacy. Meanwhile, further investigations are warranted to determine the best
      strategies, that is, timing, dosing, route of delivery, choice of stem cells and
      ex vivo modulations, to attain long-term benefits of CB stem cell therapy. 

PMID- 22964589
TI  - Translation and validation of the dietary approaches to stop hypertension for
      koreans intervention: culturally tailored dietary guidelines for Korean Americans
      with high blood pressure.
AB  - BACKGROUND: Lifestyle modification strategies such as adoption of the Dietary
      Approaches to Stop Hypertension (DASH) diet are now recognized as an integral
      part of high blood pressure (HBP) management. Although the high prevalence of HBP
      among Korean Americans (KAs) is well documented, few dietary interventions have
      been implemented in this population, in part because of a lack of culturally
      relevant nutrition education guidelines. Translating and testing the efficacy of
      culturally relevant dietary recommendations using a well-established dietary
      guideline such as DASH are imperative for promoting better cardiovascular health
      for this high-risk cultural group. OBJECTIVE: The aims of this study were to
      systematically translate and validate a culturally modified DASH for Koreans (K
      DASH) and obtain preliminary evidence of efficacy. METHODS: A 2-step approach of
      intervention translation and efficacy testing, together with close adherence to
      principles of community-based participatory research, was used to maximize
      community input. A 1-group pre-post design with 24-hour urine and 24-hour
      ambulatory blood pressure monitoring comparisons was used to test the initial
      feasibility and efficacy of the K-DASH intervention. RESULTS: A total of 28 KAs
      with HBP participated in a 10-week dietary intervention consisting of group
      education sessions and individual counseling. Both systolic blood pressure and
      diastolic blood pressure, as measured by ambulatory blood pressure monitoring,
      were significantly decreased at postintervention evaluation (systolic blood
      pressure, -4.5 mm Hg; diastolic blood pressure, -2.6 mm Hg; P < .05). Serum low
      density lipoprotein cholesterol was significantly decreased (-7.3 mg/dL; P <
      .05). Serum potassium and ascorbic acid levels were also improved in the
      reference range. Urine potassium level was significantly increased, supporting
      increased fruit and vegetable consumption. CONCLUSION: This pilot study has (a)
      demonstrated that a cultural adaptation of DASH using community-based
      participatory research methodology produced a culturally relevant and efficacious
      dietary intervention for the KAs with HBP and (b) provided strong preliminary
      evidence for the efficacy of the K-DASH intervention in reducing HBP in
      hypertensive KAs.

PMID- 22964591
TI  - Retroperitoneal fibrosis as manifestation of chronic GVHD after allogeneic
      hematopoietic SCT.

PMID- 22964592
TI  - Pre-transplant (18)F-fluorodeoxyglucose positron emission tomography-based
      survival model in patients with aggressive lymphoma undergoing high-dose
      chemotherapy and autologous SCT.
AB  - (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) documented
      response after salvage chemotherapy has been reported to impact survival in
      patients with aggressive non-Hodgkin's lymphoma, especially diffuse large B cell
      lymphoma (DLBCL) undergoing high dose chemotherapy and autologous SCT (HDC auto
      SCT). We reviewed the impact of 19 different prognostic/predictive factors before
      salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients
      with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC
      auto-SCT outcome. The Fine and Gray method for competing risk analysis and a
      regression model was used to assess the risk associated with different factors on
      outcome. Fifty-five patients had FDG-PET after salvage chemotherapy; male 65%,
      female 45%, relapsed 55%, refractory 45%, DLBCL 82%, T cell lymphoma 18%, median
      age at auto-SCT 40 years, median follow-up 42.4 months. Multivariate analysis
      identified only positive FDG-PET (P=0.04) and mediastinal involvement (P=0.05)
      with higher hazard rate of disease-specific death (model P=0.008) but only
      positive FDG-PET (P=0.01) for disease-specific events (persistent, progressive or
      relapsed disease). Cumulative incidence of disease-specific death for patients
      with 0, 1 and 2 risk factors was 5, 30 and 62%, respectively (P=0.01). Our model
      is significant and showed an increasing risk of failure with mediastinal
      involvement and post-salvage positive FDG-PET.

PMID- 22964593
TI  - Tandem autologous vs autologous plus reduced intensity allogeneic transplantation
      in the upfront management of multiple myeloma: meta-analysis of trials with
      biological assignment.
AB  - We utilized meta-analysis to compare tandem autologous (TA) hematopoietic SCT
      (auto-HSCT) or single auto-HSCT followed by reduced intensity conditioning (RIC),
      allogeneic (AR) hematopoietic SCT in the upfront management of patients with
      multiple myeloma (MM). A comprehensive search strategy of published and
      unpublished reports utilized the following entry criteria: newly diagnosed
      patients, first autologous transplantation in both arms, use of an RIC regimen
      and assignment to TA or AR based exclusively on the availability of an HLA
      matched donor. Six trials were identified yielding 1192 subjects in TA and 630 in
      AR. Patients in AR had higher likelihoods of TRM (relative risk (RR)=3.3, 95%
      confidence interval (CI)=2.2-4.8) and CR (RR=1.4, 95% CI=1.1-1.8). OS was not
      different in the first 36 months (hazard ratio (HR)=1.15, 95% CI=0.91-1.45) or
      after (HR=0.74, 95% CI=0.53-1.04) 36 months from assignment. Similar findings
      were seen for PFS. When compared with TA in the upfront management of MM, AR is
      associated with higher TRM and CR without improvement in PFS or OS.

PMID- 22964594
TI  - Second malignancies after autologous hematopoietic cell transplantation in
      children.
AB  - Childhood autologous hematopoietic cell transplant (auto-HCT) survivors can be at
      risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1487
      pediatric auto-HCT recipients to investigate the incidence and risk factors for
      SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma
      (18%), central nervous system tumors (14%) and Wilms tumor (2%). Median follow-up
      was 8 years (range, <1-21 years). SMNs were reported in 35 patients
      (AML/myelodysplastic syndrome (MDS)=13, solid cancers=20, subtype missing=2). The
      overall cumulative incidence of SMNs at 10 years from auto-HCT was 2.60%
      (AML/MDS=1.06%, solid tumors=1.30%). We found no association between SMNs risk
      and age, gender, diagnosis, disease status, time since diagnosis or use of TBI or
      etoposide as part of conditioning. OS at 5-years from diagnosis of SMNs was 33%
      (95% confidence interval (CI), 16-52%). When compared with age- and gender
      matched general population, auto-HCT recipients had 24 times higher risks of
      developing SMNs (95% CI, 16.0-33.0). Notable SMN sites included bone (N=5 SMNs,
      observed (O)/expected (E)=81), thyroid (N=5, O/E=53), breast (N=2, O/E=93), soft
      tissue (N=2, O/E=34), AML (N=6, O/E=266) and MDS (N=7, O/E=6603). Risks of SMNs
      increased with longer follow-up from auto-HCT. Pediatric auto-HCT recipients are
      at considerably increased risk for SMNs and need life-long surveillance for SMNs.

PMID- 22964595
TI  - Changes in incidence and causes of non-relapse mortality after allogeneic
      hematopoietic cell transplantation in patients with acute
      leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome
      Registry.
AB  - The outcomes for allogeneic hematopoietic cell transplantation (allo-HCT) are
      heavily influenced by non-relapse mortality (NRM). We retrospectively assessed
      the changes in the incidence and causes of NRM after allo-HCT over the past 12
      years. NRM, relapse rate and OS were analyzed using the Japan transplant outcome
      database of 6501 adult patients with acute leukemia or myelodysplastic syndrome
      who received their first allo-HCT in remission from 1997 through 2008. In
      multivariate analysis in patients aged 16-49 years, the adjusted hazard ratios
      (HRs) for NRM for 2001-2004 and 2005-2008 were 0.78 (95% confidence interval,
      0.65-0.93) and 0.64 (0.54-0.78), respectively, compared with 1997-2000. The HR
      for overall mortality in 2005-2008 was 0.81 (0.70-0.93) compared with 1997-2000.
      In patients aged 50-70 years, the HRs for NRM and overall mortality in 2005-2008
      were 0.56 (0.46-0.68) and 0.66 (0.47-0.93), respectively, compared with those in
      2001-2004. We found that causes of death that contributed to the changes in NRM
      varied among subgroups. In conclusion, our study indicated that the incidence of
      NRM after allo-HCT has significantly decreased over the past 12 years, which has
      led to an improvement of OS, and also showed reductions in NRM in subgroups
      consisting of older patients and those who received unrelated cord blood
      transplantation.

PMID- 22964596
TI  - Refinement in patient selection to reduce treatment-related mortality from
      autologous stem cell transplantation in amyloidosis.
AB  - This study sought to develop selection guidelines to determine the eligibility
      for SCT of patients with light-chain amyloidosis. Patients with biopsy-confirmed
      lightchain amyloidosis who underwent SCT between 8 March 1996 and 31 December
      2011 were reviewed in two cohorts by date of transplantation: between 8 March
      1996 and 30 June 2009 (n=410) and between 1 July 2009 and 31 December 2011
      (n=89). Also evaluated were patients who died before post-transplant day 100 to
      determine the features predictive of early death. After 1 July 2009, fewer
      transplant recipients had Mayo stage III cardiac involvement. Mortality before
      post-transplant day 100 was 10.5% (43/410) in the earlier group and 1.1% (1/89)
      in the later group. In the earlier group, one-quarter of transplant recipients
      with N-terminal pro-brain natriuretic peptide (NT-proBNP) >5000 pg/mL died by
      10.3 months. When serum troponin T was >0.06 ng/mL, 25% died at 3.7 months. The
      Mayo staging system is predictive for OS but not useful for selecting transplant
      recipients. Patients with serum troponin T >0.06 ng/mL or NT-proBNP >5000 pg/mL
      (not on dialysis) should not be considered candidates for SCT because of early
      mortality.

PMID- 22964597
TI  - Nurse and citizen.

PMID- 22964600
TI  - Increasing the consumption of breast milk in low-birth-weight infants: can it
      have an impact on necrotizing enterocolitis?
AB  - Necrotizing enterocolitis (NEC) is a disease that occurs in up to 10% of infants
      born weighing less than 1500 g at birth. Significant research has been done
      looking for ways to prevent NEC from occurring in this vulnerable population. One
      factor that has shown promise in decreasing the incidence of NEC is increased
      consumption of breast milk versus formula. This article describes the research
      related to breast milk and the decreased incidence of NEC as well as research
      related to increasing the amount of breast milk available and consumed by preterm
      neonates.

PMID- 22964601
TI  - Making the case for using donor human milk in vulnerable infants.
AB  - Vulnerable infants are at an increased risk for feeding intolerance due to
      immaturity or dysfunction (ie, congenital anomaly or obstruction) of the
      gastrointestinal system and/or hemodynamic instability. Symptoms of feeding
      intolerance include vomiting, water-loss stools, increased abdominal girth, and
      increased gastric residuals. It has been well documented that human milk provides
      optimal nutrition for infants and decreases the incidence of feeding intolerance.
      Donor human milk can be used for these at-risk infants to supplement the mother's
      own milk supply if insufficient or if the mother has decided not to or is unable
      to provide human milk for her infant. Establishing a donor human milk program
      within your institution will allow an opportunity for all vulnerable infants to
      receive an exclusive human milk diet.

PMID- 22964603
TI  - NICU nurses' lived experience: caring for infants with neonatal abstinence
      syndrome.
AB  - PURPOSE: The primary aim of this qualitative methods study was to describe the
      lived experiences of neonatal intensive care unit (NICU) nurses with ethical and
      morally challenging issues. SUBJECTS: The target population for the study was
      registered nurses working in the NICU. Interviews were completed with 16 nurses
      from 1 hospital. DESIGN: A phenomenological method design was used to describe
      NICU nurses' lived experiences with ethical and moral issues encountered in the
      NICU. METHODS: After obtaining signed consent, the principal investigator
      interviewed all participants, using a semistructured interview guide consisting
      of open-ended questions. MAIN OUTCOMES: Ethical and moral distress related to
      neonatal abstinence syndrome was the predominant outcome. PRINCIPAL RESULTS:
      Caring for infants, coping with families, and discharging infants home were the
      major concerns voiced by nurses in this study. CONCLUSIONS: Nurses in this study
      struggled with issues of beneficence and nonmaleficence and were not aware of
      scientific evidence that guides methadone management of pregnant women.

PMID- 22964604
TI  - Call for improved care for the substance-positive mother.

PMID- 22964605
TI  - Promoting and protecting infant sleep.

PMID- 22964606
TI  - Toward salience: an application of integrative, case-based, nursing education for
      neonatal advanced practice.
AB  - The purpose of this article was to present a new, integrative, case-based
      educational approach for neonatal advanced practice nursing students in a
      hybirdized long-distance program at the University of Washington. The theoretical
      background is based on a holistic, systems-based, and case-based approach to
      learning. A guideline for instructors will be included, emphasizing
      recommendations of Benner et al for teaching a sense of salience, integration,
      critical reasoning, and role formation. Such a holistic approach to neonatal
      advanced practice nursing education may maximize the unification of knowledge
      with practice and improve learning, at a time when resources are few.

PMID- 22964607
TI  - More than information: a qualitative study of parents' perspectives on neonatal
      intensive care at the extremes of prematurity.
AB  - PURPOSE: To describe parental perceptions of decision making concerning their
      extremely premature newborns who received care in a level III neonatal intensive
      care unit (NICU). SUBJECTS: Seven parents of preterm infants who were born at 24
      to 26 weeks' gestation at a western Canadian tertiary NICU. DESIGN: Qualitative,
      interpretive description, semistructured interviews. METHODS: The first author
      conducted interviews with both parents together or the mother alone. Interviews
      were recorded, transcribed, and analyzed. RESULTS: Three main themes related to
      decision making, culture shock, and relationships emerged: (1) decision making
      before and in the NICU: moving beyond information, (2) culture shock in the NICU:
      plunging into a strange land, and (3) relationships in the NICU: enduring in a
      strange land. CONCLUSIONS: Although information and decision making are
      interconnected and fundamental to parents' experiences of their preterm baby's
      NICU stay, they also identified the culture and language of the NICU and genuine
      relationships formed with healthcare professionals as significantly influencing
      their experiences.

PMID- 22964608
TI  - The premie-neuro: opportunities and challenges for standardized neurologic
      assessment of the preterm infant.
AB  - PURPOSE: To determine the interrater and test-retest reliabilities and construct
      validity of the Premie-Neuro, a standardized neurologic assessment tool for
      preterm infants. SUBJECTS: Thirty-four preterm infants (mean gestational age at
      birth 29 +/- 3.7 weeks, mean birth weight 1343.2 +/- 696.3 g) participated in the
      study. DESIGN: A prospective repeated-measures design was used to assess the
      reliability and validity of the Premie-Neuro. METHODS: The Premie-Neuro was
      administered twice on consecutive days and then weekly through 37-weeks
      postmenstrual age or hospital discharge. At discharge, infants' medical histories
      were reviewed and a Neurobiologic Risk Score (NBRS) was used to determine risk
      for poor neurodevelopmental outcomes. MAIN OUTCOME MEASURE: Premie-Neuro raw
      scores and classifications were analyzed to determine the tool's reliability.
      Construct validity was measured by determining whether the Premie-Neuro could
      discriminate between infants identified as high-risk or low-risk for
      neurodevelopmental delays by using a NBRS of 5 as the cutoff for high- and low
      risk infants. RESULTS: The intraclass correlation coefficients for interrater and
      test-retest reliability varied from 0.391 to 0.556 and from 0.493 to 0.592,
      respectively. Analysis of variance revealed that the Premie-Neuro raw scores for
      infants with NBRS > 5 were significantly worse than those for infants with NBRS <
      5 (P = .000-.010). CONCLUSIONS: The Premie-Neuro is a valid assessment tool for
      discriminating between preterm infants at high and low risk for
      neurodevelopmental delay. Interrater reliability of the Premie-Neuro was poor,
      and test-retest reliability of the Premie-Neuro was fair to moderate. The Premie
      Neuro may be acceptable for assessing groups of infants, but there is no evidence
      that reliability is sufficient for clinical decision-making for individual
      infants. More research needs to be done to improve the reliability of the Premie
      Neuro and assess other facets of the Premie-Neuro's reliability.

PMID- 22964609
TI  - Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive
      compulsive disorder nonresponsive to first-step behavior therapy.
AB  - BACKGROUND: To compare the effectiveness of second-step treatment with cognitive
      therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder
      (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP).
      METHODS: A 12-week randomized controlled trial at an outpatient clinic in the
      Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD
      treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement
      score of less than one third). These nonresponders were randomized to CT (n = 22)
      or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale.
      Statistical analyses were conducted in the intention-to-treat sample (n = 45) on
      an 'as randomized basis' and in the per-protocol sample (n = 30). Due to
      selective dropout in the fluvoxamine group, two additional sensitivity analyses
      were performed. RESULTS: Complete data could be obtained from 45 subjects (94%)
      after 12 weeks. Fifty percent of the patients refused fluvoxamine after
      randomization compared to 13% who refused CT [chi(2)(1) = 7.10; p = 0.01]. CT as
      a second-step treatment did not appear to be effective in this sample of
      nonresponders. Fluvoxamine was significantly superior to CT in the intention-to
      treat sample, in the per-protocol sample and in the two separately defined
      samples in which the sensitivity analyses were performed. CONCLUSIONS: OCD
      patients who are nonresponsive to ERP may benefit more from a switch to treatment
      with an antidepressant instead of switching to CT. In clinical practice, it may
      be important to motivate this subgroup of patients to undergo
      psychopharmacological treatment, as this may improve their outcome considerably.

PMID- 22964611
TI  - Lysosome-mediated apoptosis is associated with cathepsin D-specific processing of
      bid at Phe24, Trp48, and Phe183.
AB  - Bax-mediated permeabilization of the outer mitochondrial membrane and release of
      apoptogenic factors into the cytosol are key events that occur during apoptosis.
      Likewise, apoptosis is associated with permeabilization of the lysosomal membrane
      and release of lysosomal cathepsins into the cytosol. This report identifies
      proteolytically active cathepsin D as an important component of apoptotic
      signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome
      mediated cell death is associated with degradation of Bax sequestering 14-3-3
      proteins, cleavage of the Bax activator Bid, and translocation of Bax to
      mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be
      reproduced by enforced lysosomal membrane permeabilization, using the
      lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We
      identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and
      Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from
      purified mitochondria, indicating that the fragments generated are functionally
      active. Moreover, apoptosis was associated with cytosolic acidification, thereby
      providing a more favorable environment for the cathepsin D-mediated cleavage of
      Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated
      cytochrome c release by proteolytic activation of Bid.

PMID- 22964610
TI  - Early LQT2 nonsense mutation generates N-terminally truncated hERG channels with
      altered gating properties by the reinitiation of translation.
AB  - Mutations in the human ether-a-go-go-related gene (hERG) result in long QT
      syndrome type 2 (LQT2). The hERG gene encodes a K(+) channel that contributes to
      the repolarization of the cardiac action potential. We have previously shown that
      hERG mRNA transcripts that contain premature termination codon mutations are
      rapidly degraded by nonsense-mediated mRNA decay (NMD). In this study, we
      identified a LQT2 nonsense mutation, Q81X, which escapes degradation by the
      reinitiation of translation and generates N-terminally truncated channels. RNA
      analysis of hERG minigenes revealed equivalent levels of wild-type and Q81X mRNA
      while the mRNA expressed from minigenes containing the LQT2 frameshift mutation,
      P141fs+2X, was significantly reduced by NMD. Western blot analysis revealed that
      Q81X minigenes expressed truncated channels. Q81X channels exhibited decreased
      tail current levels and increased deactivation kinetics compared to wild-type
      channels. These results are consistent with the disruption of the N-terminus,
      which is known to regulate hERG deactivation. Site-specific mutagenesis studies
      showed that translation of the Q81X transcript is reinitiated at Met124 following
      premature termination. Q81X co-assembled with hERG to form heteromeric channels
      that exhibited increased deactivation rates compared to wild-type channels.
      Mutant channels also generated less outward current and transferred less charge
      at late phases of repolarization during ventricular action potential clamp. These
      results provide new mechanistic insight into the prolongation of the QT interval
      in LQT2 patients. Our findings indicate that the reinitiation of translation may
      be an important pathogenic mechanism in patients with nonsense and frameshift
      LQT2 mutations near the 5' end of the hERG gene.

PMID- 22964612
TI  - Oncogenesis recapitulates embryogenesis via the hypoxia pathway: morphoproteomics
      and biomedical analytics provide proof of concept and therapeutic options.
AB  - BACKGROUND: Hypoxia (3 to 5% oxygen) is essential in maintaining the plasticity
      of embryonic stem cells and permitting their transformation via epithelial
      mesenchymal transition(EMT) and mesenchymal-epithelial transition(MET) into
      tissues and organs of the developing fetus. Similarly, a relatively hypoxic
      microenvironment supports the development of tumor cells with stemness and
      epithelial-mesenchymal properties and capabilities. At the same time, such
      adaptation results in the tumor cells becoming relatively resistant to
      chemotherapy and radiation therapy and promotes intravasation into blood vessels
      with metastasis. In this context, current therapeutic strategies designed to
      target tumoral angiogenesis could promote stemness and EMT by rendering tumor
      cells more hypoxic, leading to chemoradioresistance and metastatic and recurrent
      disease. OBJECTIVE: The purpose of this report is to present a conceptual model
      that illustrates the impact of an hypoxic microenvironment on the signal
      transduction pathways involved in the hypoxia pathway. We will show the molecular
      connectivity and correlative association of these pathways with protein analytes
      in both embryogenesis and oncogenesis in order to strengthen our hypothesis that
      oncogenesis recapitulates embryogenesis. Finally, we propose to use the model as
      a basis for the construction of combinatorial, therapeutic options from existing
      pharmaceutical and nutraceutical agents that may obviate tumoral adaptation to
      hypoxia. METHODS: Morphoproteomics and biomedical analytics. APPLICATION AND
      RESULTS: Archival data retrieved from morphoproteomic analysis of glioblastoma
      multiforme(GBM) cases revealed proteomic correlates of tumoral necrosis and
      associated hypoxia pathway signaling. Biomedical analytics using Ingenuity
      Pathway Analysis (IPA) showed comparative validation of the hypoxia pathway, as
      demonstrated by morphoproteomics in GBM, both with the hypoxia-induced genes in
      neuroblastoma and with the networks associated with embryogenesis. Additionally,
      therapeutic agents known to have activity against various components of the
      hypoxia pathway (identified by morphoproteomic analysis in GBM) were validated
      using UNIPROT identifiers entered into IPA and Path Designer. These therapies
      also connected with the hypoxia signature in neuroblastoma and embryogenesis.
      CONCLUSION: The application of morphoproteomics to define the presence of an
      adaptive hypoxia pathway in GBM accords with biomedical analytics in the
      demonstration of concordant interaction with the hypoxia signature in
      neuroblastoma and embryogenesis, providing proof of concept that oncogenesis
      recapitulates embryogenesis. This approach also validates a new combinatorial
      therapeutic strategy targeting the hypoxia pathway and designed to prevent
      tumoral adaptation, chemoradioresistance and recurrent disease.

PMID- 22964613
TI  - BRAFV600E mutation testing in fine needle aspirates of thyroid nodules: potential
      value of real-time PCR.
AB  - The BRAF(V600E) mutation is a valuable adjunctive diagnostic tool to ultrasound
      (US)-guided fine-needle aspiration (US-FNA). The objective of this study was to
      investigate the potential value of realtime PCR to detect BRAF(V600E) mutation.
      This study included 447 thyroid nodules in 420 patients who underwent US-FNA and
      BRAF(V600E) mutation analysis using dual priming oligonucleotide-based multiplex
      polymerase chain reaction (DPO-PCR) and real-time PCR. We calculated and compared
      the diagnostic performances of DPO-PCR and real-time PCR to detect BRAF(V600E)
      mutation in the thyroid nodules. Receiver operating characteristic (ROC) analysis
      was used to quantify the cut-off value of the Ct values of BRAF(V600E) mutation
      on real-time PCR. Optimal thresholds were determined (Youden index). We also
      compared the diagnostic performances between DPO-PCR and real-time PCR after
      applying the cut-off value on real-time PCR. Sensitivity, accuracy, and NPV were
      significantly higher in real-time PCR than DPO-PCR. When the optimal cut-off
      value of 32.4 at Ct values of BRAF(V600E) mutation was adjusted on real-time PCR,
      sensitivity was 66.2% and specificity was 100%. Sensitivity, accuracy, and NPV of
      real-time PCR were also significantly higher than DPO-PCR. In contrast,
      specificity and PPV were not significantly different between DPO-PCR and real
      time PCR. Real time PCR can be a promising diagnostic method in detecting
      BRAF(V600E) mutation using optimal cut-off value.

PMID- 22964614
TI  - Inflammation associated with neoplastic colonic polyps.
AB  - Little is known about the significance of inflammation in neoplastic colon
      polyps: tubular, tubulovillous, and villous polyps/adenomas (TVPs) and
      hyperplastic/serrated polyps (HSPs). We undertake this study to ascertain the
      significance of acute and chronic inflammation in neoplastic polyps. Eighty-one
      consecutive, randomized TVPs and fifty-four randomized HSPs accessioned in the
      UCHC surgical pathology laboratory were selected for final analysis. The TVPs
      display increased acute and chronic inflammation compared to normal and adjacent
      non-dysplastic colonic mucosa. Adenoma size correlates with degree of acute and
      chronic inflammation. TVPs show increased overall acute and chronic inflammation
      compared to HSPs of the same size. This difference was statistically highly
      significant (p<.001). The number of adenomas exhibiting high grade dysplasia was
      insufficient to evaluate the relationship between polyp inflammation, polyp size,
      and degree of dysplasia. The HSPs showed significantly lower incidence and
      severity of acute and chronic inflammation compared to the TVPs. No correlation
      was seen in the HSP group between polyp size and acute or chronic inflammation.
      The prevalence of IBD was higher in patients with HSP showing acute inflammation
      than in the general population, but this statistic may be skewed by the low
      overall incidence of acute inflammation in the HSP group.

PMID- 22964615
TI  - A combination of CD15/CD10, CD64/CD33, CD16/CD13 or CD11b flow cytometric
      granulocyte panels is sensitive and specific for diagnosis of myelodysplastic
      syndrome.
AB  - Flow cytometry (FCM) is a reproducible and objective technique that may be useful
      in the diagnosis of myelodysplastic syndrome (MDS) by detecting abnormal
      immunophenotypes specific to MDS. We investigated 5 granulocyte/monocyte panels
      by FCM to find a sensitive and specific combination of panels in order to
      discriminate MDS from non-clonal hematologic disorders. Bone marrow aspirates
      from 35 patients with MDS and 25 patients with non-clonal hematologic disorders
      were studied. We performed FCM using 5 granulocyte/monocyte panels
      (CD15/CD10/CD45, CD64/CD33/CD45, CD16/CD13/CD45, CD16/CD11b/CD45, and
      CD56/CD19/CD7/CD45) to examine the positive rate in MDS and controls, and to find
      an optimal combination that maximizes the detection rate of MDS. In MDS, the
      number of abnormal immunophenotypes per 5 granulocytic and 5 monocytic panels
      were 2.1 +/- 1.2 and 2.2 +/- 1.4. The rates were higher than the controls (P<
      0.001, respectively). As the number of employed panels increased, the percent
      values of abnormal immunophenotypes increased (P=0.002). The maximum rate of
      abnormal immunophenotype was 89.7% in MDS patients, especially 100.0% in normal
      karyotype, when a combination of three panels, CD15/CD10/CD45, CD64/CD33/CD45,
      and either CD16/CD13/CD45 or CD16/CD11b/CD45 was used. This study demonstrates
      that a combination of CD15/CD10, CD64/CD33, CD16/CD13 or CD11b granulocyte panels
      in FCM is sensitive and specific for diagnosis of MDS.

PMID- 22964616
TI  - Molecular mechanisms of carbapenem resistance in Enterobacter cloacae clinical
      isolates from Korea and clinical outcome.
AB  - We investigated the molecular mechanisms of carbapenem resistance in clinical
      isolates of Enterobacter cloacae and their clinical characteristics.
      Nonreplicable E. cloacae isolates were recovered from six cancer patients and one
      patient with liver cirrhosis at a tertiary-care hospital in Korea between 2002
      and 2009. Two patients who were considered to have a true infection caused by
      these microorganisms have died. All isolates produced AmpC beta-lactamases,
      including ACT-1, ACT-2, MIR-3 and DHA-1, and CTX-M- or SHV-type extended-spectrum
      beta-lactamase. Two isolates produced plasmid-borne VIM-2 carbapenemase. All
      probes specific for bla(AmpC) genes hybridized with I-CeuI chromosomal fragments
      were also recognized by a probe specific for 16S rDNA, suggesting a chromosomal
      location. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that a
      major outer membrane protein, OmpF, was absent in all isolates. PFGE of XbaI
      digested DNA were considered to be unrelated. The results of our study suggest
      that the chromosomal AmpC beta-lactamase with impermeability in E. cloacae
      clinical isolates implicated in reduced carbapenem susceptibility. Although
      carbapenem-resistant E. cloacae isolates were isolated in a few patients in our
      study, the clinical outcomes were grave. Therefore, the patients colonized or
      infected by carbapenem-resistant E. cloacae isolates should gain attention of
      antibiotic therapy.

PMID- 22964617
TI  - Primary cutaneous adenomyoepithelioma.
AB  - Adenomyoepitheliomas are biphasic tumors composed of epithelial and myoepithelial
      components in varying proportions. They are commonly reported in the breast,
      uncommonly in salivary glands, and rarely in the lungs and vulva. Recent
      molecular analysis has shown that p27/kip-1 protein may play a role in their
      development. Primary cutaneous adenomyoepithelioma is an extremely rare tumor
      with only three well documented cases reported to date. We report a case of
      primary cutaneous adenomyoepithelioma with histological and immunohistochemical
      characterization, and discuss their differential diagnosis, biologic behavior and
      treatment strategies.

PMID- 22964618
TI  - Simultaneous detection of Gaucher's disease and renal involvement of non
      Hodgkin's lymphoma: the first Asian case report and a review of literature.
AB  - Gaucher's disease (GD) is a rare autosomal recessive (AR) disorder characterized
      by a deficiency of glucocerebrosidase (glucosylceramidase, acid beta
      glucosidase). This enzyme deficiency results in an accumulation of sphingolipids
      in the cells of GD patients, which may contribute to the dysregulation of the
      immune system, B-cell dysfunction and expression of specific cytokines such as
      interleukin (IL) -1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF).
      Accumulated substrate may directly affect the patient's immunity and pose a
      higher risk for cancer, especially hematologic malignancies. However, recent
      large-scale studies suggest that the relative risks of GD and hematologic
      malignancies are not statistically significant and, therefore, their association
      with each other remains controversial. In this report, we present the first Asian
      GD case where the patient was simultaneously diagnosed with a non-Hodgkin's
      lymphoma. A renal biopsy confirmed that the patient had diffuse large B-cell
      lymphoma (DLBCL). A bone marrow study during lymphoma staging revealed Gaucher
      cells with abundant fibrillary, blue-gray cytoplasm and a wrinkled, tissue paper
      like appearance. Subsequently, an acid beta-glucosidase (GbA) gene mutation study
      demonstrating two heterozygote mutations, G202R (c.721G>A; p.G241R), a known
      pathogenic mutation, and a novel mutation R277C (c.946C>T; p.R316C) prompted the
      diagnosis of GD. Previous case reports have demonstrated concurrent GD and
      lymphoma in type 1 GD patients, with 40% of patients diagnosed with GD when a
      lymphoma is detected during disease evaluation. In Korea, GD cases with the G202R
      gene mutation have been reported in neuropathic patients with a very low
      frequency. To our knowledge, this case represents the first observation of the
      G202R mutation in a type 1 GD patient associated with lymphoma. Furthermore, this
      report is the first patient with DLBCL with kidney involvement along with GD.

PMID- 22964619
TI  - Spurious hemolysis does not influence the reliability of digoxin testing on
      Siemens RXL MAX and Roche Cobas e601.
AB  - Little information is available on the influence of spurious hemolysis on digoxin
      immunoassays. Seventeen consecutive, non-hemolyzed, sodium-heparin samples were
      divided in three aliquots. The first was immediately centrifuged and tested for
      hemolysis index (HI), as well as plasma digoxin on Siemens RXL MAX using the
      Siemens Dimension Flex and Roche Cobas e601 by electrochemiluminescent (ECLIA)
      technique. The second and third aliquots were subjected to mechanical hemolysis
      by aspirating the blood one and two times through a thin needle. The
      concentration of digoxin measured on Siemens RXL MAX was significantly decreased
      from aliquot #A, to aliquot #B (-4%), and aliquot #C (-6%), but in none of the
      hemolyzed specimens the 10% bias was exceeded. No significant variation was
      observed by measuring plasma digoxin on Roche Cobas.

PMID- 22964620
TI  - Clinical, biochemical, and genetic analysis of two korean patients with
      trichorhinophalangeal syndrome type I and growth hormone deficiency.
AB  - Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant
      hereditary disorder characterized by sparse hair, bulbous nose, long philtrum,
      thin upper lip, and skeletal abnormalities including cone-shaped epiphyses,
      shortening of the phalanges, and short stature. TRPSI is caused by mutations in
      the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both
      patients (a 17-year-old-female and a 14-year-old male) had typical clinical
      findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment
      with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in
      growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7 +/
      0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH
      stimulation test, had a poor response with rhGH therapy and GH therapy was
      discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two
      mutations were found. Patient 1 had a heterozygous mutation c.2520dupT
      (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known
      nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report
      Korean patients with mutation of TRPS1.

PMID- 22964621
TI  - Paroxysmal nocturnal hemoglobinuria with deletion of chromosome 13q (q12q14): a
      case report and review of the literature.
AB  - A normal karyotype is usually present in cases of classic paroxysmal nocturnal
      hemoglobinuria (PNH), whereas chromosomal abnormalities involving chromosome
      bands 13q12 to 13q14 (13q12q14) are frequently found in various hematologic
      malignancies, including chronic lymphoblastic leukemia (CLL) and myelodysplastic
      syndrome (MDS). Here, we present a case of a 55-year-old male patient with PNH
      who had a deletion of chromosome 13q [del(13q)]. He presented with cough, fever,
      and pancytopenia. Flow cytometry of the patient's peripheral blood demonstrated
      that 21.7% and 21.5% of the erythrocytes were CD59 and CD55 deficient,
      respectively, and 63.5% of the granulocytes were FLAER and CD24 deficient.
      Examination of the bone marrow indicated that blasts were not increased but mild
      dyshematopoietic features were present. Conventional cytogenetic analysis and
      fluorescence in situ hybridization revealed a deletion of chromosome 13q
      (q12q14). The patient received an allogeneic hematopoietic stem cell
      transplantation. Whether this abnormality can be considered as an evidence of MDS
      in the setting of overt PNH requires an evaluation in the future.

PMID- 22964622
TI  - The effect of recentrifugation of serum separator tubes on concentration of serum
      analytes.
AB  - In clinical laboratories, sometimes there is a need to recentrifuge the original
      tubes ("clot" tubes) in order to better clarify and clean the serum or plasma for
      further analysis. Also, the original tubes are recentrifuged to ensure there is
      an adequate volume of serum or plasma for multiple repeating or different tests,
      and/or to run additional tests that are ordered hours after the original analysis
      was completed. In our practice, we have encountered that recentrifugation of
      original tubes, including those with gel separators, does slightly change the
      concentration of analytes. Although there are two reports on the effect of
      recentrifugation on serum potassium concentration [1, 2], to the best of our
      knowledge there are no other studies to show the impact of re-centrifugation on
      the concentrations of multiple analytes that are routinely measured as part of
      "metabolic panel". This study investigated the effect of recentrifugation on the
      concentrations of glucose, sodium, potassium, chloride, BUN, creatinine,
      bicarbonate, calcium, phosphorus, and magnesium.

PMID- 22964623
TI  - Physical inactivity: associated diseases and disorders.
AB  - A sedentary lifestyle is a very serious worldwide problem, especially in North
      America and Europe. Unfortunately, physical inactivity, which has progressively
      increased over the past several decades, significantly increases the risk of
      numerous diseases/disorders, including several forms of cancer, diabetes,
      hypertension, coronary and cerebrovascular diseases, overweight/obesity, and all
      cause mortality, among others. Unless there is a reversal of this sedentary
      lifestyle, the incidence of these diseases/disorders will increase, life
      expectancy will decrease, and medical costs will continue to rise.

PMID- 22964624
TI  - Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for
      the treatment of asthma?
AB  - Histone deacetylase inhibitors have emerged as a new class of anti-cancer
      therapeutics due to their potent anti-proliferative and apoptotic effects in
      malignant cells. Accumulating evidence is indicating that histone deacetylase
      inhibitors may also have potential clinical utility in non-oncological
      applications, including asthma. However, the potential of histone deacetylase
      inhibitors in asthma remains controversial. For example, the mechanisms of action
      of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal
      models of allergic airways disease are conflicting. Further, there is evidence
      suggesting potential problems associated with histone deacetylase 2 inhibition
      and conventional glucocorticosteroid therapy. Similarly, disparate findings are
      emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is
      becoming apparent that the mechanism of action may not be related to histone
      deacetylase inhibition activity per se. Further, there is only limited evidence
      that these compounds possess anti-inflammatory effects in models of asthma. In
      this review, we provide an overview of the biology of the metal-dependent and
      sirtuin deacetylases in the context of asthma. The controversies surrounding the
      potential use of histone deacetylase inhibitors in asthma are discussed and
      future directions involving the investigation of more specific analogues are
      explored.

PMID- 22964625
TI  - Major blunders by noted pathologists.

PMID- 22964626
TI  - High prevalence of gastroesophageal reflux symptoms in patients with non
      alcoholic fatty liver disease associated with serum levels of triglyceride and
      cholesterol but not simple visceral obesity.
AB  - BACKGROUND/AIMS: Visceral obesity is commonly involved in the pathogenesis of
      gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease
      (NAFLD). However, other characteristic factors different from visceral obesity
      are associated with the pathogenesis of NAFLD. We investigated the prevalence of
      GERD symptoms in patients with NAFLD and its associated risk factors. METHODS:
      NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms
      were evaluated by using a frequency scale for the symptoms of GERD. RESULTS: GERD
      symptom score and its prevalence rate were higher in the NAFLD group (7.4 +/-
      0.7, 37%) than those seen in the control groups (4.5 +/- 0.4, 20%), which was
      independent of sex, age, and body mass index (BMI). GERD symptoms were correlated
      with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r =
      0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive
      insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms
      of the NAFLD group were significantly severer in the higher group of T-CHO and TG
      levels than those in the lower group. Multivariate analysis proved that risk
      factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31-11.9) and T-CHO
      (OR 3.39, 95% CI 1.11-10.3). CONCLUSION: The severity and prevalence of GERD
      symptoms in patients with NAFLD were high, which was associated with serum levels
      of TG and T-CHO but not BMI.

PMID- 22964627
TI  - Body image in patients with posttraumatic stress disorder after childhood sexual
      abuse and co-occurring eating disorder.
AB  - BACKGROUND: Body image is a multidimensional construct with cognitive-affective,
      behavioral and perceptive components. Survivors of childhood sexual abuse report
      a disturbance of the cognitive-affective component of their body image but not of
      the perceptive component. It has not yet been examined whether and how the
      behavioral component is affected. Also, it is still unknown whether the
      disturbances might be due to the influence of co-occurring eating disorders.
      SAMPLING AND METHODS: The cognitive-affective and behavioral components of the
      body image of 84 female participants with posttraumatic stress disorder (PTSD)
      after childhood sexual abuse (31 with a co-occurring eating disorder) and 53
      healthy participants were assessed via the Dresden Body Image Inventory (Dresdner
      Korperbildfragebogen-35, DKB-35) and the Body Image Avoidance Questionnaire
      (BIAQ). RESULTS: PTSD patients reported significantly higher negative scores on
      all DKB-35 subscales (p < 0.001) and the BIAQ (p = 0.002; p < 0.001). Results
      remained consistent after accounting for the influence of co-occurring eating
      disorders (p = 0.021; p = 0.001; p < 0.001). CONCLUSIONS: Results show for the
      first time that the behavioral component of the body image is impaired in female
      patients with PTSD in addition to the cognitive-affective component. This is not
      solely due to a comorbid eating disorder. The effect of established treatments on
      the body image of PTSD patients should be evaluated and new treatment modules
      should be developed and tested, if necessary.

PMID- 22964629
TI  - Shock about heat shock in cancer.
AB  - The transcription factor heat shock factor 1 (HSF1) is the master regulator of
      the heat shock response. It is crucial for cell homeostasis and implicated in
      aging, neurodegenerative disease and cancer. Although induction by HSF1 of the
      expression of molecular chaperones and other regulators of protein quality
      control, both folding and degradation, is well established, the precise and
      detailed transcriptional network that HSF1 regulates in cancer is poorly
      understood. An important new study identifies an HSF1-regulated transcriptional
      program in highly malignant cells that is surprisingly distinct from the
      traditional heat shock response. The results have significant implications for
      our molecular understanding of cancer and the development of new therapies.

PMID- 22964630
TI  - The critical role of cyclin D2 in cell cycle progression and tumorigenicity of
      glioblastoma stem cells.
AB  - Cancer stem cells are believed to be responsible for tumor initiation and
      development. Much current research on human brain tumors is focused on the stem
      like properties of glioblastoma stem cells (GSCs). However, little is known about
      the molecular mechanisms of cell cycle regulation that discriminate between GSCs
      and differentiated glioblastoma cells. Here we show that cyclin D2 is the cyclin
      that is predominantly expressed in GSCs and suppression of its expression by RNA
      interference causes G1 arrest in vitro and growth retardation of GSCs xenografted
      into immunocompromised mice in vivo. We also demonstrate that the expression of
      cyclin D2 is suppressed upon serum-induced differentiation similar to what was
      observed for the cancer stem cell marker CD133. Taken together, our results
      demonstrate that cyclin D2 has a critical role in cell cycle progression and the
      tumorigenicity of GSCs.

PMID- 22964631
TI  - Gene signature critical to cancer phenotype as a paradigm for anticancer drug
      discovery.
AB  - Malignant cell transformation commonly results in the deregulation of thousands
      of cellular genes, an observation that suggests a complex biological process and
      an inherently challenging scenario for the development of effective cancer
      interventions. To better define the genes/pathways essential to regulating the
      malignant phenotype, we recently described a novel strategy based on the
      cooperative nature of carcinogenesis that focuses on genes synergistically
      deregulated in response to cooperating oncogenic mutations. These so-called
      'cooperation response genes' (CRGs) are highly enriched for genes critical for
      the cancer phenotype, thereby suggesting their causal role in the malignant
      state. Here, we show that CRGs have an essential role in drug-mediated anticancer
      activity and that anticancer agents can be identified through their ability to
      antagonize the CRG expression profile. These findings provide proof-of-concept
      for the use of the CRG signature as a novel means of drug discovery with
      relevance to underlying anticancer drug mechanisms.

PMID- 22964633
TI  - Recruitment of the tumour suppressor protein p73 by Kaposi's Sarcoma Herpesvirus
      latent nuclear antigen contributes to the survival of primary effusion lymphoma
      cells.
AB  - Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of Kaposi's Sarcoma
      (KS) and two rare lymphoproliferative disorders, primary effusion lymphoma (PEL)
      and the plasmablastic variant of multicentric Castleman's disease (MCD). The KSHV
      latency-associated nuclear antigen-1 (LANA), required for the replication and
      maintenance of latent viral episomal DNA, is involved in the transcriptional
      regulation of viral and cellular genes and interacts with different cellular
      proteins, including the tumour suppressor p53. Here, we report that LANA also
      recruits the p53-related nuclear transcription factor p73, which influences
      cellular processes like DNA damage response, cell cycle progression and
      apoptosis. Both the full-length isoform TAp73alpha, as well as its dominant
      negative regulator DeltaNp73alpha, interact with LANA. LANA affects TAp73alpha
      stability and sub-nuclear localisation, as well as TAp73alpha-mediated
      transcriptional activation of target genes. We observed that the small-molecule
      inhibitor Nutlin-3, which disrupts the interaction of p53 and p73 with MDM2,
      induces apoptotic cell death in p53 wild-type, as well as p53-mutant PEL cell
      lines, suggesting a possible involvement of p73. The small-molecule RETRA, which
      activates p73 in the context of mutant p53, leads to the induction of apoptosis
      in p53-mutant PEL cell lines. RNAi-mediated knockdown of p73 confirmed that these
      effects depend on the presence of the p73 protein. Furthermore, both Nutlin-3 and
      RETRA disrupt the LANA-p73 interaction in different PEL cell lines. These results
      suggest that LANA modulates p73 function and that the LANA-p73 interaction may
      represent a therapeutic target to interfere with the survival of latently KSHV
      infected cells. 

PMID- 22964632
TI  - Immunobiology of human mucin 1 in a preclinical ovarian tumor model.
AB  - Epithelial ovarian cancer is an aggressive malignancy, with a low 5-year median
      survival. Continued improvement on the development of more effective therapies
      depends in part on the availability of adequate preclinical models for in vivo
      testing of treatment efficacy. Mucin 1 (MUC1) glycoprotein is a tumor-associated
      antigen overexpressed in ovarian cancer cells, making it a potential target for
      immune therapy. To create a preclinical mouse model for MUC1-positive ovarian
      tumors, we generated triple transgenic (Tg) mice that heterozygously express
      human MUC1(+/-) as a transgene, and carry the conditional K-rasG12D oncoallele
      (loxP-Stop-loxP-K-ras(G12D/+)) and the floxed Pten gene (Pten/(loxP/loxP)).
      Injection of Cre recombinase-encoding adenovirus (AdCre) in the ovarian bursa of
      triple (MUC1KrasPten) Tg mice triggers ovarian tumors that, in analogy to human
      ovarian cancer, express strongly elevated MUC1 levels. The tumors metastasize
      loco-regionally and are accompanied by high serum MUC1, closely mimicking the
      human disease. Compared with the KrasPten mice with tumors, the MUC1KrasPten mice
      show increased loco-regional metastasis and augmented accumulation of CD4+Foxp3+
      immune-suppressive regulatory T cells. Vaccination of MUC1KrasPten mice with type
      1 polarized dendritic cells (DC1) loaded with a MUC1 peptide (DC1-MUC1) can
      circumvent tumor-mediated immune suppression in the host, activate multiple
      immune effector genes and effectively prolong survival. Our studies report the
      first human MUC1-expressing, orthotopic ovarian tumor model, reveal novel MUC1
      functions in ovarian cancer biology and demonstrate its suitability as a target
      for immune-based therapies.

PMID- 22964634
TI  - Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG
      methylation in human breast cancer.
AB  - The complexity of gene regulation has created obstacles to defining mechanisms
      that establish the patterns of gene expression characteristic of the different
      clinical phenotypes of breast cancer. TFAP2C is a transcription factor that has a
      critical role in the regulation of both estrogen receptor-alpha (ERalpha) and c
      ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct
      sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines. Comparing the
      genomic binding sites for TFAP2C, we identified that glutathione peroxidase
      (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter
      of the GPX1 gene. Knockdown of TFAP2C, but not the related factor TFAP2A,
      resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity
      correlated with endogenous GPX1 expression and overexpression of exogenous GPX1
      induced GPX activity and significantly increased resistance to tert-butyl
      hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory
      region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter
      and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where
      GPX1 promoter methylation was associated with gene silencing, treatment with 5'
      aza-2-deoxycytidine (5'-aza-dC) (an inhibitor of DNA methylation) allowed TFAP2C
      to bind to the GPX1 promoter resulting in the activation of GPX1 RNA and protein
      expression. Methylation of the GPX1 promoter was identified in ~20% of primary
      breast cancers and a highly significant correlation between the TFAP2C and GPX1
      expression was confirmed when considering only those tumors with an unmethylated
      promoter, whereas the related factor, TFAP2A, failed to demonstrate a
      correlation. The results demonstrate that TFAP2C regulates the expression of
      GPX1, which influences the redox state and sensitivity to oxidative stress
      induced by peroxides. Given the established role of GPX1 in breast cancer, the
      results provide an important mechanism for TFAP2C to further influence
      oncogenesis and progression of breast carcinoma cells.

PMID- 22964635
TI  - Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells.
AB  - Rho signaling is increasingly recognized to contribute to invasion and
      metastasis. In this study, we discovered that metastasis-associated protein
      S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting
      S100A4 to the Rho pathway. Glutathione S-transferase pull-down and
      immunoprecipitation assays demonstrated that S100A4 specifically and directly
      binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to
      Rhotekin is calcium-dependent and uses residues distinct from those bound by
      active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex
      with active RhoA. Using RNA interference, we determined that suppression of both
      S100A4 and Rhotekin leads to loss of Rho-dependent membrane ruffling in response
      to epidermal growth factor, an increase in contractile F-actin 'stress' fibers
      and blocks invasive growth in three-dimensional culture. Accordingly, our data
      suggest that interaction of S100A4 and Rhotekin permits S100A4 to complex with
      RhoA and switch Rho function from stress fiber formation to membrane ruffling to
      confer an invasive phenotype. 

PMID- 22964636
TI  - BMP-specific SMADs function as novel repressors of PDGFA and modulate its
      expression in ovarian granulosa cells and tumors.
AB  - Platelet-derived growth factor alpha (PDGFA) is frequently upregulated in various
      cancers and thought to function as a key player in the development and
      progression of tumor growth by regulating aspects of cell proliferation,
      angiogenesis and metastasis. However, the mechanism by which it is upregulated is
      not fully understood. Previously, we demonstrated that conditional deletion of
      two transcription factors that signal for the bone morphogenetic proteins (Smad1
      and Smad5) in ovarian granulosa cells causes metastatic granulosa cell tumors
      (GCTs) in female mice and phenocopies human juvenile GCTs (JGCTs). Smad1/5 double
      conditional knockout tumors, as well as human JGCTs, are highly vascularized,
      hemorrhagic and mitotically active. Expression analysis of these tumors and their
      metastases revealed a significant upregulation of key proliferation and pro
      angiogenic factors such as Pdgfa, Pdgfb and Vegf. We examined whether these genes
      were direct targets of SMAD1 and SMAD5. Knockdown of SMAD1 and SMAD5 in mouse
      primary granulosa cells and a human GCT-derived cell line (COV434) resulted in
      upregulation of PDGFA, but not PDGFB nor VEGF. We identified several putative
      SMAD1/5-binding sites in the PDGFA promoter, and chromatin immunoprecipitation
      and reporter assays demonstrated that SMAD1/5 interact with the PDGFA promoter to
      regulate its activity. Further, SMAD1/5 antagonize the activity of the
      transcription factor Sp1, a well-known positive regulator of PDGFA, by inhibiting
      its occupancy at a key regulatory site on the proximal PDGFA promoter.
      Collectively, our studies establish that loss of SMAD1/5 leads to upregulation of
      PDGFA in ovarian granulosa cells, and that a novel regulatory interaction exists
      between the BR-SMADs and Sp1 in controlling PDGFA expression during granulosa
      cell tumorigenesis.

PMID- 22964637
TI  - The tumor suppressor Caliban regulates DNA damage-induced apoptosis through p53
      dependent and -independent activity.
AB  - We previously identified Caliban (Clbn) as the Drosophila homolog of human
      Serologically defined colon cancer antigen 1 gene and demonstrated that it could
      function as a tumor suppressor in human non-small-cell lung cancer (NSCLC) cells,
      although its mode of action was unknown. Herein, we identify roles for Clbn in
      DNA damage response. We generate clbn knockout flies using homologous
      recombination and demonstrate that they have a heightened sensitivity to
      irradiation. We show that normal Clbn function facilitates both p53-dependent and
      -independent DNA damage-induced apoptosis. Clbn coordinates different apoptosis
      pathways, showing a two-stage upregulation following DNA damage. Clbn has
      proapoptotic functions, working with both caspase and the proapoptotic gene Hid.
      Finally, ecotopic expression of clbn(+) in NSCLC cells suppresses tumor formation
      in athymic nude mice. We conclude that Caliban is a regulator of DNA damage
      induced apoptosis, functioning as a tumor suppressor in both p53-dependent and 
      independent pathways.

PMID- 22964638
TI  - Effect of miR-21 and miR-30b/c on TRAIL-induced apoptosis in glioma cells.
AB  - Glioblastoma is the most frequent brain tumor in adults and is the most lethal
      form of human cancer. Despite the improvements in treatments, survival of
      patients remains poor. To define novel pathways that regulate susceptibility to
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in glioma, we
      have performed genome-wide expression profiling of microRNAs (miRs). We show that
      in TRAIL-resistant glioma cells, levels of different miRs are increased, and in
      particular, miR-30b/c and -21. We demonstrate that these miRs impair TRAIL
      dependent apoptosis by inhibiting the expression of key functional proteins. T98G
      sensitive cells treated with miR-21 or -30b/c become resistant to TRAIL.
      Furthermore, we demonstrate that miR-30b/c and miR-21 target respectively the 3'
      untranslated region of caspase-3 and TAp63 mRNAs, and that those proteins mediate
      some of the effects of miR-30 and -21 on TRAIL resistance, even in human
      glioblastoma primary cells and in lung cancer cells. In conclusion, we show that
      high expression levels of miR-21 and -30b/c are needed to maintain the TRAIL
      resistant phenotype, thus making these miRs as promising therapeutic targets for
      TRAIL resistance in glioma.

PMID- 22964640
TI  - miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia.
AB  - MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post
      transcriptionally, are involved in many complex cellular processes. Several
      miRNAs are differentially expressed in hematopoietic tissues and play important
      roles in normal differentiation, but, when aberrantly regulated, contribute to
      the abnormal proliferation and differentiation of leukemic cells. Recently, we
      reported that a small subset of miRNAs is differentially expressed in acute
      promyelocytic leukemia (APL) blasts and is modulated by treatment with all-trans
      retinoic acid (ATRA). In particular, PML/RARalpha-positive blasts from APL
      patients display lower levels of miRNA let-7c, a member of the let-7 family, than
      normal promyelocytes and its expression increases after ATRA treatment. In this
      study, we investigated the effects of let-7c in acute myeloid leukemia (AML)
      cells. We found that ectopic expression of let-7c promotes granulocytic
      differentiation of AML cell lines and primary blasts. Moreover, we identified
      PBX2, a well-known homeodomain protein whose aberrant expression enhances HoxA9
      dependent leukemogenesis, as a novel let-7c target that may contribute to the AML
      phenotype. Together, these studies raise the possibility that perturbation of the
      let-7c-PBX2 pathway may have a therapeutic value in AML. 

PMID- 22964639
TI  - Inhibition of metastasis by HEXIM1 through effects on cell invasion and
      angiogenesis.
AB  - We report on the role of hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1)
      as an inhibitor of metastasis. HEXIM1 expression is decreased in human metastatic
      breast cancers when compared with matched primary breast tumors. Similarly we
      observed decreased expression of HEXIM1 in lung metastasis when compared with
      primary mammary tumors in a mouse model of metastatic breast cancer, the polyoma
      middle T antigen (PyMT) transgenic mouse. Re-expression of HEXIM1 (through
      transgene expression or localized delivery of a small molecule inducer of HEXIM1
      expression, hexamethylene-bis-acetamide) in PyMT mice resulted in inhibition of
      metastasis to the lung. Our present studies indicate that HEXIM1 downregulation
      of HIF(-)1alpha protein allows not only for inhibition of vascular endothelial
      growth factor-regulated angiogenesis, but also for inhibition of compensatory pro
      angiogenic pathways and recruitment of bone marrow-derived cells (BMDCs). Another
      novel finding is that HEXIM1 inhibits cell migration and invasion that can be
      partly attributed to decreased membrane localization of the 67 kDa laminin
      receptor, 67LR, and inhibition of the functional interaction of 67LR with
      laminin. Thus, HEXIM1 re-expression in breast cancer has therapeutic advantages
      by simultaneously targeting more than one pathway involved in angiogenesis and
      metastasis. Our results also support the potential for HEXIM1 to indirectly act
      on multiple cell types to suppress metastatic cancer.

PMID- 22964641
TI  - CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via
      AKT and ERK signaling.
AB  - CIB1 is a 22-kDa regulatory protein previously implicated in cell survival and
      proliferation. However, the mechanism by which CIB1 regulates these processes is
      poorly defined. Here, we report that CIB1 depletion in SK-N-SH neuroblastoma and
      MDA-MB-468 breast cancer cells promotes non-apoptotic, caspase-independent cell
      death that is not initiated by increased outer mitochondrial membrane
      permeability or translocation of apoptosis-inducing factor to the nucleus.
      Instead, cell death requires nuclear GAPDH accumulation. Furthermore, CIB1
      depletion disrupts two commonly dysregulated, oncogenic pathways-PI3K/AKT and
      Ras/MEK/ERK, resulting in a synergistic mechanism of cell death, which was
      mimicked by simultaneous pharmacological inhibition of both pathways, but not
      either pathway alone. In defining each pathway's contributions, we found that AKT
      inhibition alone maximally induced GAPDH nuclear accumulation, whereas MEK/ERK
      inhibition alone had no effect on GAPDH localization. Concurrent GAPDH nuclear
      accumulation and ERK inhibition were required, however, to induce a significant
      DNA damage response, which was critical to subsequent cell death. Collectively,
      our results indicate that CIB1 is uniquely positioned to regulate PI3K/AKT and
      MEK/ERK signaling and that simultaneous disruption of these pathways
      synergistically induces a nuclear GAPDH-dependent cell death. The mechanistic
      insights into cell death induced by CIB1 interference suggest novel molecular
      targets for cancer therapy.

PMID- 22964642
TI  - Nrf2 is controlled by two distinct beta-TrCP recognition motifs in its Neh6
      domain, one of which can be modulated by GSK-3 activity.
AB  - Identification of regulatable mechanisms by which transcription factor NF-E2 p45
      related factor 2 (Nrf2) is repressed will allow strategies to be designed that
      counter drug resistance associated with its upregulation in tumours that harbour
      somatic mutations in Kelch-like ECH-associated protein-1 (Keap1), a gene that
      encodes a joint adaptor and substrate receptor for the Cul3-Rbx1/Roc1 ubiquitin
      ligase. We now show that mouse Nrf2 contains two binding sites for beta
      transducin repeat-containing protein (beta-TrCP), which acts as a substrate
      receptor for the Skp1-Cul1-Rbx1/Roc1 ubiquitin ligase complex. Deletion of either
      binding site in Nrf2 decreased beta-TrCP-mediated ubiquitylation of the
      transcription factor. The ability of one of the two beta-TrCP-binding sites to
      serve as a degron could be both increased and decreased by manipulation of
      glycogen synthase kinase-3 (GSK-3) activity. Biotinylated-peptide pull-down
      assays identified DSGIS(338) and DSAPGS(378) as the two beta-TrCP-binding motifs
      in Nrf2. Significantly, our pull-down assays indicated that beta-TrCP binds a
      phosphorylated version of DSGIS more tightly than its non-phosphorylated
      counterpart, whereas this was not the case for DSAPGS. These data suggest that
      DSGIS, but not DSAPGS, contains a functional GSK-3 phosphorylation site.
      Activation of GSK-3 in Keap1-null mouse embryonic fibroblasts (MEFs), or in human
      lung A549 cells that contain mutant Keap1, by inhibition of the phosphoinositide
      3-kinase (PI3K)-protein kinase B (PKB)/Akt pathway markedly reduced endogenous
      Nrf2 protein and decreased to 10-50% of normal the levels of mRNA for prototypic
      Nrf2-regulated enzymes, including the glutamate-cysteine ligase catalytic and
      modifier subunits, glutathione S-transferases Alpha-1 and Mu-1, haem oxygenase-1
      and NAD(P)H:quinone oxidoreductase-1. Pre-treatment of Keap1(-/-) MEFs or A549
      cells with the LY294002 PI3K inhibitor or the MK-2206 PKB/Akt inhibitor increased
      their sensitivity to acrolein, chlorambucil and cisplatin between 1.9-fold and
      3.1-fold, and this was substantially attenuated by simultaneous pre-treatment
      with the GSK-3 inhibitor CT99021. 

PMID- 22964643
TI  - RAD52 inactivation is synthetically lethal with deficiencies in BRCA1 and PALB2
      in addition to BRCA2 through RAD51-mediated homologous recombination.
AB  - Synthetic lethality is an approach to study selective cell killing based on
      genotype. Previous work in our laboratory has shown that loss of RAD52 is
      synthetically lethal with BRCA2 deficiency, while exhibiting no impact on cell
      growth and viability in BRCA2-proficient cells. We now show that this same
      synthetically lethal relationship is evident in cells with deficiencies in BRCA1
      or PALB2, which implicates BRCA1, PALB2 and BRCA2 in an epistatic relationship
      with one another. When RAD52 was depleted in BRCA1- or PALB2-deficient cells, a
      severe reduction in plating efficiency was observed, with many abortive attempts
      at cell division apparent in the double-depleted background. In contrast, when
      RAD52 was depleted in a BRCA1- or PALB2-wildtype background, a negligible
      decrease in colony survival was observed. The frequency of ionizing radiation
      induced RAD51 foci formation and double-strand break-induced homologous
      recombination (HR) was decreased by 3- and 10-fold, respectively, when RAD52 was
      knocked down in BRCA1- or PALB2-depleted cells, with minimal effect in BRCA1- or
      PALB2-proficient cells. RAD52 function was independent of BRCA1 status, as
      evidenced by the lack of any defect in RAD52 foci formation in BRCA1-depleted
      cells. Collectively, these findings suggest that RAD52 is an alternative repair
      pathway of RAD51-mediated HR, and a target for therapy in cells deficient in the
      BRCA1-PALB2-BRCA2 repair pathway. 

PMID- 22964645
TI  - Transport properties of graphene functionalized with molecular switches.
AB  - We provide a theory of the electronic transport properties of a graphene layer
      functionalized with molecular switches. Our considerations are motivated by the
      spiropyran-merocyanine system which is non-polar in its ring-closed spiropyran
      form and zwitterionic in its ring-open merocyanine form. The reversible switching
      between these two isomers affects the carriers in graphene through the associated
      change in the molecular dipole moment, turning the graphene layer into a sensor
      of the molecular switching state. We present results for both the quasiclassical
      (Boltzmann) and the quantum coherent regimes of transport. Quite generally, we
      find a linear sensitivity of the conductance on the molecular dipole moment
      whenever quantum interference effects play an essential role which contrasts with
      a quadratic (and typically weaker) dependence when quantum interference is
      absent.

PMID- 22964644
TI  - Oncogenic KRAS-induced epiregulin overexpression contributes to aggressive
      phenotype and is a promising therapeutic target in non-small-cell lung cancer.
AB  - KRAS mutations are one of the most common driver mutations in non-small-cell lung
      cancer (NSCLC) and finding druggable target molecules to inhibit oncogenic KRAS
      signaling is a significant challenge in NSCLC therapy. We recently identified
      epiregulin (EREG) as one of several putative transcriptional targets of oncogenic
      KRAS signaling in both KRAS-mutant NSCLC cells and immortalized bronchial
      epithelial cells expressing ectopic mutant KRAS. In the current study, we found
      that EREG is overexpressed in NSCLCs harboring KRAS, BRAF or EGFR mutations
      compared with NSCLCs with wild-type KRAS/BRAF/EGFR. Small interfering RNAs
      (siRNAs) targeting mutant KRAS, but not an siRNA targeting wild-type KRAS,
      significantly reduced EREG expression in KRAS-mutant and EREG-overexpressing
      NSCLC cell lines. In these cell lines, EREG expression was downregulated by MEK
      and ERK inhibitors. Importantly, EREG expression significantly correlated with
      KRAS expression or KRAS copy number in KRAS-mutant NSCLC cell lines. Further
      expression analysis using 89 NSCLC specimens showed that EREG was predominantly
      expressed in NSCLCs with pleural involvement, lymphatic permeation or vascular
      invasion and in KRAS-mutant adenocarcinomas. In addition, multivariate analysis
      revealed that EREG expression is an independent prognostic marker and EREG
      overexpression in combination with KRAS mutations was associated with an
      unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG
      overexpressing NSCLC cells, siRNA-mediated EREG silencing inhibited anchorage
      dependent and -independent growth and induced apoptosis. Our findings suggest
      that oncogenic KRAS-induced EREG overexpression contributes to an aggressive
      phenotype and could be a promising therapeutic target in oncogenic KRAS-driven
      NSCLC.

PMID- 22964646
TI  - R25C mutation in the NKX2.5 gene in Italian patients affected with non-syndromic
      and syndromic congenital heart disease.
AB  - AIMS: Heterozygous mutations in the transcription factor Nkx2.5 indicate a
      genetic cause for congenital heart diseases (CHDs) in human beings. The present
      study aimed to assess the prevalence of NKX2.5 mutations in Italian patients with
      sporadic non-syndromic and syndromic CHD, as well as to appraise any genotype
      phenotype correlations. METHODS: One hundred Italian patients affected with CHD
      (90 had sporadic non-syndromic CHD and 10 had syndromic CHD) were screened for
      NKX2.5 mutations. The coding region and flanking regions involved in gene
      splicing of the CSX/NKX2.5 gene were amplified from genomic DNA by PCR, and
      mutational analysis was performed using denaturing high performance liquid
      chromatography and DNA sequencing. RESULTS: One previously reported NKX2.5
      mutation (c.73C>T, p.R25C) was identified in two of the 100 CHD patients (2%). We
      have detected the p.R25C alteration in a woman showing aneurysm of the membranous
      septum, aortic coarctation and bicuspid aortic valve, that was a different
      phenotype from those previously reported, and for the first time in a patient
      with syndromic CHD with Down's syndrome (posterior ventricular septal defect,
      atrial septal defect, left superior cava vein ' sinus, and patent ductus
      arteriosus). CONCLUSION: Our results confirm that NKX2.5 mutations are not a
      common cause of CHD; furthermore, the p.R25C variation may increase
      susceptibility to development of CHD in patients with and without chromosomal
      abnormalities.

PMID- 22964647
TI  - Effect of hyperuricemia on the blood pressure response to antihypertensive agents
      in hospitalized elderly patients.
AB  - AIMS: As elevated serum uric acid (SUA) is an independent risk factor for
      hypertension, we examined whether baseline SUA may influence the blood pressure
      (BP) response to antihypertensive medications. METHODS: Data from 1648 inpatients
      with essential, uncontrolled hypertension on admission were analyzed
      retrospectively. Patients taking loop or thiazide diuretics or hypouricemic
      agents were excluded. The BP response to treatment was based on the BP change
      from admission (baseline) to discharge. RESULTS: The mean age was 66.7 +/- 11.5
      years, the average BP was 156.1/85.5 mmHg and the average estimated glomerular
      filtration rate (eGFR) was 80.07 +/- 21.69 ml/min per 1.73 m. Twenty-five percent
      of the patients had chronic kidney disease and 32% had diabetes. The average
      duration of hospitalization was 14.3 +/- 5.3 days. In 1149 patients with normal
      renal function (eGFR >=60 ml/min per 1.73 m), those with hyperuricemia (SUA >420
      MUmol/l in men and >360 MUmol/l in women) had more metabolic disorders (P <
      0.05), higher baseline diastolic BP (P < 0.05), greater antihypertensive
      therapeutic intensity score (TIS) at baseline and discharge (P < 0.01), more
      diuretic use at discharge (P < 0.01) and less systolic BP reduction in response
      to antihypertensive therapy (P < 0.01). After adjustment for age, diabetes, BMI,
      baseline BP, lipid disorders, baseline TIS and eGFR, multiple linear regression
      using the data from all patients indicated that hyperuricemia was associated with
      a 5.3 mmHg less systolic BP reduction [95% confidence interval (CI): 3.1-7.4
      mmHg, P < 0.01] in men, and a 2.6 mmHg less systolic BP reduction (95% CI: 0.5
      4.6 mmHg, P = 0.02) in women. CONCLUSION: Hyperuricemia may be an independent
      risk factor for BP control in elderly hypertensive patients during
      hospitalization.

PMID- 22964648
TI  - Genesis of remote conditioning: action at a distance--'hypotheses non fingo'?
AB  - Remote ischemic preconditioning is the phenomenon whereby brief episodes of
      ischemia-reperfusion applied in a distant organ or tissue render the myocardium
      resistant to infarction. The discovery of remote conditioning was not a
      serendipitous finding, but, rather, was predicted by mathematical modeling. In
      the current review, we describe how the hypothesis for remote conditioning was
      formulated and tested, how the paradigm has expanded to encompass a spectrum of
      remote triggers, and summarize the progress that has been made in elucidating the
      mechanisms responsible for this intriguing form of cardioprotection.

PMID- 22964649
TI  - The many faces of Behcet's disease.
AB  - A 23-year-old man with fevers, night sweats, lymphadenopathy, worsening vision,
      and aphthous ulcers was diagnosed with Behcet's disease. Multiple diagnostic
      imaging modalities were used to identify various multisystem complications
      associated with Behcet's disease including vascular thomboses, mediastinal
      fibrosis, chylothoraces, chylopericardium and coronary artery aneurysms. 

PMID- 22964650
TI  - Pyramid heart: uncommon sequel of a common disease.
AB  - A 40-year-old woman presented 19 years after ring-annuloplastyfor rheumatic
      mitral regurgitation. Long-standing rheumatic heartdisease resulted in an unusual
      finding on her chest radiograph. 

PMID- 22964651
TI  - Cardiovascular involvement in patients with pseudoexfoliation syndrome.
AB  - AIM: Pseudoexfoliation (PEX) syndrome, diagnosed by ocular examination, is a
      common disorder of the extracellular matrix. Previous studies have demonstrated
      accumulation of PEX material in the walls of blood vessels and myocardium. We
      aimed to investigate whether PEX is associated with cardiovascular involvement
      using carotid ultrasound measurements and myocardial tissue Doppler imaging
      (TDI). METHODS: Thirty-six PEX patients and 34 age-matched and sex-matched
      healthy controls who had no PEX material were included. Fasting blood samples
      were taken and the following data were obtained from all cases: myocardial TDI
      measurements, the mean carotid intima-media thickness (IMT), total carotid plaque
      area and number. RESULTS: There were no significant differences between the
      groups regarding clinical and biochemical data. The peak systolic TDI velocities
      at the septal (septal S) and lateral annuli (lateral S), and the isovolumic
      contraction velocity at the lateral annulus [lateral isovolumic contraction
      velocity (IVC)] were significantly lower in patients with PEX, than in controls
      (P = 0.001, <0.001 and 0.016, respectively) whereas IMT, total carotid plaque
      area and number were significantly higher (P = 0.002, 0.035 and 0.033,
      respectively). In a logistic regression analysis including age, septal S, lateral
      S, lateral IVC, IMT, total carotid plaque area and number, septal S, lateral S
      and IMT were significantly associated with PEX, (P = 0.035, 0.011 and 0.035,
      respectively). CONCLUSION: Peak systolic TDI velocities were significantly lower
      and IMT was significantly increased in patients with PEX. However, PEX was weakly
      associated with carotid plaque measurements.

PMID- 22964652
TI  - Impaired microvascular endothelial function in vitamin D-deficient diabetic
      nephropathy patients.
AB  - AIMS: This study aims to compare microvascular endothelial function between
      vitamin D-deficient and nondeficient groups of patients with diabetic
      nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive
      protein (hsCRP) were also measured. METHODS: This prospective cross-sectional
      study involved 70 patients with diabetic nephropathy; 40 were categorized into
      the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50
      nmol/l], whereas 30 patients were categorized to the group with deficient serum
      25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using
      laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and
      sodium nitroprusside were used to determine endothelium-dependent and independent
      vasodilatation. RESULTS: Mean age of patients was 56.7 +/- 3.8 years; 50 were
      men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient
      group was 69.4 +/- 2.9 nmol/l; the level in the vitamin D-deficient group was
      42.1 +/- 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in
      the vitamin D-deficient group compared with the vitamin D-nondeficient group
      (23.6 +/- 2.7 versus 37.3 +/- 3.8 arbitrary units, P = 0.004). No significant
      differences were observed between the two groups in their hsCRP levels, mean age,
      estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) and glycosylated haemoglobin. CONCLUSION: Microvascular
      endothelial function was significantly reduced in diabetic nephropathy patients
      with deficient vitamin D levels compared with those with nondeficient levels.

PMID- 22964653
TI  - Copeptin:  a new marker in cardiology.
AB  - Copeptin, the C-terminal part of the prohormone of vasopressin (AVP), is released
      together with AVP in stoichiometric concentrations reflecting an individual's
      stress level. Copeptin has come to be regarded as an important marker for
      identifying high-risk patients and predicting outcomes in a variety of diseases.
      It improves the clinical value of commonly used biomarkers and the tools of risk
      stratification. Elevated AVP activation and higher copeptin concentrations have
      been previously described in acute systemic disorders. However, the field that
      could benefit the most from the introduction of copeptin measurements into
      practice is that of cardiovascular disease. Determination of copeptin level
      emerges as a fast and reliable method for differential diagnosis, especially in
      acute coronary syndromes. A particular role in the diagnosis of acute myocardial
      infarction (AMI) is attributed to the combination of copeptin and troponin.
      According to available sources, such a combination allows AMI to be ruled out
      with very high sensitivity and negative predictive value. Moreover, elevated
      copeptin levels correlate with a worse prognosis and a higher risk of adverse
      events after AMI, especially in patients who develop heart failure. Some authors
      suggest that copeptin might be valuable in defining the moment of the
      introduction of treatment and its monitoring in high-risk patients. The
      introduction of copeptin into clinical practice might also provide a benefit on a
      larger scale by suggesting changes in the allocation of financial resources
      within the health system. Although very promising, further larger trials are
      required in order to assess the clinical benefits of copeptin in everyday
      practice and patient care.

PMID- 22964654
TI  - Editorial: engaging trainees in health care improvement throughout medical
      education.

PMID- 22964655
TI  - Letter to the editor: the UMass Memorial Quality Scholars program at year three:
      a response to the editorial by Drs Myers and Jaeger.

PMID- 22964656
TI  - Letter to the editor: "boutique" quality assurance.

PMID- 22964657
TI  - Healthcare delivery in the wake of the SCOTUS decision: a call to make a
      difference!

PMID- 22964658
TI  - High-flow nasal cannulae for respiratory support of preterm infants: a review of
      the evidence.
AB  - BACKGROUND: High-flow nasal cannulae (HFNC) are gaining in popularity as a form
      of non-invasive respiratory support for preterm infants in neonatal intensive
      care units around the world. They are proposed as an alternative to nasal
      continuous positive airway pressure (NCPAP) in a variety of clinical situations,
      including post-extubation support, primary therapy from birth and 'weaning' from
      NCPAP. OBJECTIVES: To present and discuss the available evidence for the use of
      HFNC in the preterm population. METHODS: An internet-based literature search for
      relevant, original research articles (both randomised studies and not) on the use
      of HFNC in preterm infants was undertaken. RESULTS: A total of 19 studies were
      included in the review. Distending pressure generated by HFNC in preterm infants
      increases with increasing flow rate and decreasing infant size and varies
      according to the amount of leak around the prongs. HFNC may be as effective as
      NCPAP at improving respiratory parameters such as tidal volume and work of
      breathing in preterm infants, but probably only at flow rates >2 litres/min. The
      efficacy and safety of HFNC in preterm infants remain to be determined.
      CONCLUSIONS: There is growing evidence of the feasibility of HFNC as an
      alternative to other forms of non-invasive ventilation in preterm infants.
      However, there remains uncertainty about the efficacy and safety of HFNC in this
      population. Until the results of larger randomised trials are known, widespread
      use of HFNC to treat preterm infants cannot be recommended.

PMID- 22964659
TI  - The synthesis and characterisation of homo- and heterobimetallic 1,14,2,9- and
      1,14,2,10-M2C2B10 14-vertex metallacarboranes.
AB  - A high-yielding synthesis of the 13-vertex cobaltacarborane 4-Cp-4,1,12-closo
      CoC(2)B(10)H(12) is described and this compound used to prepare the known 14
      vertex species 1,14-Cp(2)-1,14,2,10-closo-Co(2)C(2)B(10)H(12) (II) and 1-(p
      cymene)-14-Cp-1,14,2,10-closo-RuCoC(2)B(10)H(12) (IV), the latter by a new route.
      The related species 1,14-Cp(2)-2,10-Me(2)-1,14,2,10-closo-Co(2)C(2)B(10)H(10) (1)
      and 1,14-(eta-C(9)H(7))(2)-1,14,2,10-closo-Co(2)C(2)B(10)H(12) (2) are also
      reported. Polyhedral expansion of 4,1,8-CoC(2)B(10) compounds affords a different
      isomer of the 14-vertex bimetallacarboranes, 1,14,2,9-Co(2)C(2)B(10), and three
      examples, 1,14-Cp(2)-1,14,2,9-closo-Co(2)C(2)B(10)H(12) (3), 1,14-Cp(2)-2,9-Me(2)
      1,14,2,9-closo-Co(2)C(2)B(10)H(10) (4) and 1,14-(eta-C(9)H(7))(2)-1,14,2,9-closo
      Co(2)C(2)B(10)H(12) (5), are prepared and characterised. Patterns in (11)B NMR
      chemical shifts and in <delta(11)B>, the weighted average (11)B chemical shift,
      within and between related isomers of the 14-vertex compounds II and 1-5 are
      discussed. Compounds II, IV, 2, 4 and 5 were studied crystallographically, with
      cage C atom positions in these and related bicapped hexagonal antiprismatic
      1,14,2,x-M(2)C(2)B(10) species analysed by the Vertex-to-Centroid Distance
      method.

PMID- 22964660
TI  - Epigenetic silencing of DKK2 and Wnt signal pathway components in human ovarian
      carcinoma.
AB  - Wnt/beta-Catenin signaling dysregulation is involved in tumorigenesis.
      Furthermore, epigenetic modification of the Dickkopf (DKK) family (DKK1-DKK4) has
      been shown to be important in Wnt signaling regulation. In this study, the role
      of DKK2, a Wnt antagonist, in epithelial ovarian cancer (EOC) was evaluated by
      examining the expression and methylation of DKK2 in SKOV3 and ES-2 ovarian cancer
      cell lines and 78 tissues collected from patients (50 ovarian carcinoma, 20
      benign tumor and 8 normal ovarian tissues). DKK2 is highly downregulated in EOCs;
      however, DKK2 expression levels are higher in both normal tissues and benign
      tumors. In most cases of ovarian carcinoma, DKK2 is methylated, compared with the
      more common unmethylated form present in benign tumors and normal ovarian
      tissues. Additionally, DKK2 may be epigenetically silenced by methylation in
      higher grades and stages of EOC. Functional analysis revealed that overexpression
      of DKK2 suppressed malignant cell growth and invasion in SKOV3 and ES-2 cell
      lines. The expression of the downstream genes of Wnt signaling, including beta
      catenin, c-Myc and cyclin D1, was decreased in DKK2-transfected cells compared
      with mock cells. The expression of matrix metalloproteinase-2 and focal adhesion
      kinase were also decreased in DKK2 transfectants, supporting findings indicating
      inhibition of cell migration and invasion. This report provides novel indications
      that DKK2 is a unique hypermethylated target gene in EOC and that DKK2 may
      contribute to tumorigenesis in EOC through the Wnt/beta-catenin signaling
      mechanisms.

PMID- 22964661
TI  - Prevalence of allostatic overload syndrome in patients with chronic
      cardiovascular disease.

PMID- 22964662
TI  - Elevated plasma cytokines in Japanese patients with eosinophilic esophagitis and
      gastroenteritis.
AB  - BACKGROUND/AIM: The role of Th2-type cytokines in development of eosinophilic
      esophagitis (EoE) has been largely revealed, whereas research on the pathogenesis
      of eosinophilic gastroenteritis (EGE) has not been widely performed. We
      investigated the possible involvement of Th2-type cytokines in EGE by measuring
      plasma cytokine concentrations in patients with EGE as well as those with EoE.
      METHODS: 18 patients with EoE, 18 with EGE, and 30 normal volunteers were
      enrolled in the study. Plasma concentrations of five cytokines (thymic stromal
      lymphopoietin, IL-5, IL-13, IL-15, and eotaxin-3) were measured using Milliplex
      assays. Clinical characteristics of the patients and plasma cytokine levels were
      then compared. RESULTS: Higher proportions of patients with EoE and those with
      EGE showed elevated plasma concentrations of IL-5 and IL-15 as compared to the
      normal controls. There was also a positive correlation between IL-5 and IL-15,
      and also with blood eosinophil count. The plasma concentrations of these
      cytokines tended to be higher in cases with EGE than in those with EoE, though
      there were overlaps in cytokine levels among the patients and controls.
      CONCLUSION: Similar increases in plasma IL-5 and IL-15 were observed in patients
      with EoE and those with EGE.

PMID- 22964663
TI  - A new model of binding of rifampicin and its amino analogues as zwitterions to
      bacterial RNA polymerase.
AB  - Seven new benzyl (3-9) and four new phenethyl (10-13) amino analogues of ansa
      macrolide rifampicin (1) were synthesized using the optimised method of reductive
      amination. Structures of 3-13 in solution were determined by 1D and 2D NMR and FT
      IR methods whereas the energetically most favoured conformation of amino
      analogues was calculated with the use of the PM5 method. Spectroscopic and semi
      empirical studies revealed the presence of zwitterionic forms of all 3-13
      analogues in solutions containing water traces. (1)H-(15)N HSQC and (1)H-(15)N
      HMBC in combination with (1)H-(1)H COSY and (1)H-(13)C HMBC two dimensional
      spectroscopic methods unambiguously evidenced that the presence of the
      zwitterionic form of ansa-macrolides was a consequence of proton transfer from
      the O(8)-H phenolic group to the secondary amine moiety within 3-13 structures.
      (1)H-(1)H NOESY studies indicated two different orientations of the substituent
      introduced at the C(3) position for benzyl and phenethyl amino analogues of
      rifampicin and their similar conformation within the ansa-bridges in solution. FT
      IR studies of the deprotonation of molecule and comparison of these data with
      those for indicated 3-13 C(8)=O double bond character after formation of
      zwitterions in solution. Results of an antibacterial test against Gram-(-) and
      Gram-(+) strains were compared with detailed structural information on new
      analogues of 3-13 to indicate some structure-activity relationships. Molecular
      recognition studies of 1 and 12 inhibitors at the binding site of bacterial RNA
      polymerase (RNAP) as zwitterions revealed key intermolecular interactions and led
      to the proposition of a new model of RNAP inhibition, which explains significant
      differences in antibacterial properties of rifampicin and its analogues.

PMID- 22964664
TI  - Preoperative anemia predicts thrombosis and free flap failure in microvascular
      reconstruction.
AB  - Patients undergoing microvascular reconstruction are often anemic from a
      combination of iatrogenic hemodilution and acute blood losses. No major clinical
      study describes the impact of preoperative anemia on free flap morbidity. The
      plastic surgery service at a high-volume academic center performed 156 free flaps
      among 147 patients from December 2005 to December 2010. One hundred thirty-two
      had a preoperative hemoglobin (Hb) or hematocrit (Hct), with mean values of
      11.8+/-2.4 g/dL and 35.2%+/-7.0%, respectively. The overall failure rate was 9%
      (12/132), primarily from vascular thrombosis (6/12). Through logistic regression
      analysis, Hb and Hct were significant predictors of flap failure (P<0.005) and
      vascular thrombosis (P<0.05). Fisher exact test revealed a significant increase
      in failure risk at Hct level less than 30% (Hb<10 g/dL) (relative risk, 4.76,
      P=0.006), and probit analysis demonstrated an exposure-response relationship to
      decreased Hct level (P<0.005). These findings support that preoperative anemia
      could significantly impact free flap morbidity.

PMID- 22964665
TI  - Utility outcome scores for unilateral facial paralysis.
AB  - BACKGROUND: Facial paralysis is a debilitating condition. Dynamic and static
      facial reanimation remains a challenge for plastic surgeons and requires
      important resources. Our objective was to quantify the health state utility
      assessment (ie, utility score outcomes) of living with unilateral facial
      paralysis. METHODS: Utility assessments using visual analog scale, time trade
      off, and standard gamble were used to obtain utility outcome scores for
      unilateral facial paralysis from a prospective sample of the general population
      and medical students. RESULTS: A total number of 123 individuals prospectively
      participated in the study. All measures (visual analog scale, time trade-off, and
      standard gamble) for unilateral facial paralysis [0.56+/-0.18, 0.78+/-0.21, and
      0.79+/-0.21 respectively] were significantly different (P<0.0001) from the
      corresponding outcome scores for monocular blindness [0.61+/-0.21, 0.83+/-0.21,
      and 0.85+/-0.18, respectively] and binocular blindness [0.33+/-0.18, 0.65+/-0.28,
      and 0.65+/-0.29, respectively]. Linear regression analysis using age, race,
      income, and education as predictors of each of the utility scores for facial
      paralysis showed no statistical significance. CONCLUSIONS: In samples of the
      general population and medical students, all utility score outcome measures for
      facial paralysis were lower than those for monocular blindness. Our sample
      population, if faced with unilateral facial paralysis, would theoretically
      undergo facial reanimation procedures with a willingness to sacrifice 8 years of
      life and be willing to undergo a procedure with a 21% chance of mortality to
      attain perfect health, respectively.

PMID- 22964666
TI  - The impact of residency and fellowship training on the practice of microsurgery
      by members of the american society for surgery of the hand.
AB  - PURPOSE: The purpose of this study was to assess the microsurgical training
      background of current members of the American Society for Surgery of the Hand
      (ASSH) and then determine the impact that prior training had on current
      microsurgical practice. METHODS: A 174-item anonymous Web-based survey was sent
      to all active ASSH members. Items addressed prior residency and fellowship
      training, practice setting, and training, comfort, and practice of specific
      microsurgical procedures. Data were analyzed using frequency tables, cross
      tabulations, chi tests, and other established statistical methods. RESULTS:
      Surveys were received from 377 of 2019 ASSH members (18.7% response rate).
      Residency training was in orthopedics (n=249, 66.9%), plastic surgery (n=56,
      15.1%), or general surgery (n=55, 14.8%). Fellowship training was in orthopedic
      (n=242, 65.1%), combined (n=65, 17.5%), and plastic surgery (n=15, 4%) programs.
      Microsurgical procedures involving nerves were performed by 96.6% of surgeons
      (n=337), with no significant differences between surgeons trained in plastic
      surgery versus orthopedic surgery residencies, and no differences between those
      who had completed orthopedic versus combined fellowships. Of the surgeons
      completing the survey, 56.1% (n=208) performed general microvascular procedures,
      50% (n=179) performed replantations, and 30.6% (n=113) performed free flaps. Hand
      surgeons who completed plastic surgery residencies were more likely to perform
      general microvascular procedures, replantations, and free flaps than surgeons
      trained in orthopedic residencies. When comparing training in orthopedic and
      combined fellowships, there was no difference in performance of replantations,
      free flaps, general microvascular surgery, or microsurgical procedures involving
      nerves. CONCLUSIONS: Training backgrounds have a substantial impact on current
      microsurgical practice, with residency having the most significant effect.
      Specifically, hand surgeons trained in plastic surgery residency programs are
      more likely to perform replantations, free tissue transfer, and general
      microvascular surgery than those who completed orthopedic residencies. Fellowship
      training background does not significantly affect microsurgical practice.

PMID- 22964667
TI  - The impact of living with a functional and aesthetic nasal deformity after
      primary rhinoplasty: a utility outcomes score assessment.
AB  - BACKGROUND: Revision rhinoplasty for functional deformities can be both an
      aesthetic and reconstructive surgical challenge. We set out to quantify the
      health state utility assessment of living with the physical appearance of nasal
      asymmetry along with having nasal obstruction. The use of utility scores has
      helped to establish the health burden of living with various medical conditions.
      We sought to quantify living with a health state of nasal asymmetry with nasal
      obstruction after primary rhinoplasty using utility outcome scores. METHODS: We
      used previously validated utility outcome measures to quantify the health burden
      of this clinical scenario in 128 prospective subjects. These subjects were from a
      sample of the population and medical students recruited to complete a survey to
      determine the utility outcome score of revision rhinoplasty using visual analog
      scale (VAS), time trade-off (TTO), and standard gamble (SG) tests to obtain
      utility scores for revision rhinoplasty. Linear regression and Student t test
      were used for statistical analysis. RESULTS: All measures (VAS, TTO, and SG) for
      functional nasal deformity (0.80+/-0.13, 0.90+/-0.12, and 0.91+/-0.13,
      respectively) of the 128 prospective subjects participating in this online study
      were significantly different (P<0.005) from the corresponding scores for
      monocular blindness (0.63+/-0.15, 0.85+/-0.16, and 0.85+/-0.19, respectively) and
      binocular blindness (0.38+/-0.18, 0.66+/-0.25, and 0.69+/-0.24, respectively).
      Being white was inversely related to the VAS utility scores for rhinoplasty
      (P<0.05). Additionally, female sex was positively correlated to the TTO score.
      Age, income, and education were not predictors of utility scores. CONCLUSIONS: In
      a sample of the population and medical students, VAS, TTO, and SG utility scores
      for revision rhinoplasty were determined and can be compared objectively with
      other health states and diseases with known utility scores. In a preoperative
      setting, women were objectively willing to potentially "trade" more years of life
      to treat a functional nasal deformity. If faced with a deformed nose after
      primary rhinoplasty, our sample population would consent to undergo a revision
      rhinoplasty procedure with a theoretical 9% chance of mortality and were willing
      to trade 3.6 years of their remaining life.

PMID- 22964668
TI  - Factors associated with failed hardware salvage in high-risk patients after
      microsurgical lower extremity reconstruction.
AB  - BACKGROUND: Lower extremity hardware salvage remains challenging in patients with
      complex comorbidities. The purpose of this study was to identify factors
      associated with failed hardware salvage after microsurgical lower extremity
      reconstruction. METHODS: A retrospective, institutional review board-approved
      review was performed of patients who underwent lower extremity hardware salvage
      via free tissue transfer from 2004 to 2010. Outcomes were binarized into
      successful versus failed hardware salvage, with failure defined as nonelective
      removal. Patient demographics, wound characteristics, microbiology, and pathology
      were compared. RESULTS: Thirty-four patients underwent lower extremity hardware
      salvage via free tissue transfer, with an average follow-up of 3.2 years (range,
      0.3-7.0 years). Of these patients, 15 (44.1%) had successful hardware salvage and
      19 (55.9%) required hardware removal. By demographics, a higher prevalence of
      multiple comorbidities was found in patients with failed hardware salvage. Wound
      characteristics revealed a significantly longer time to hardware coverage and
      longer duration of intravenous antibiotics in failed versus successful hardware
      salvage patients (38.9 vs 9.3 weeks, P=0.02; 6.5 vs 4.1 weeks, P=0.03,
      respectively). Initial wound cultures demonstrated a significantly higher
      frequency of positive growth in patients with failed versus successful hardware
      salvage (100.0% vs 57.1%, P=0.003). Initial pathology revealed a borderline
      significantly higher frequency of chronic osteomyelitis in failed versus
      successful salvage patients (66.7% vs 33.3%, P=0.08). CONCLUSIONS: In this
      retrospective review of microsurgical lower extremity reconstruction, factors
      associated with failed hardware salvage included multiple comorbidities, longer
      time to hardware coverage, increased duration of intravenous antibiotics,
      positive initial wound cultures, and chronic osteomyelitis on initial pathology.

PMID- 22964669
TI  - The impact of fiberwire, fiberloop, and locking suture configuration on flexor
      tendon repairs.
AB  - PURPOSE: Suture technique, suture material, and the number of strands all play
      critical roles in achieving optimal strength of flexor tendon repairs. We
      evaluated the contribution to the tensile strength of flexor tendon repair using
      the strongest suture material, Fiberwire, and the best surgical technique
      (locking configuration) using 2- and 4-strand core repair to see what factor
      played the most important role in tendon repair. METHODS: Human cadaver flexor
      tendons were harvested and repaired in a randomized fashion using locking
      configuration as derived from Pennington's report. Ten tendons per group were
      repaired using either 4-0 Fiberloop, 4-0 Fiberwire, or 2-0 Fiberwire. During load
      to-failure testing, visible gap force and maximum tensile strength were
      statistically analyzed. RESULTS: All flexor tendon repairs failed by suture
      pullout. The 4-strand 4-0 Fiberwire double-Pennington repair was found to be
      significantly stronger than the 4-strand 4-0 Fiberloop single-Pennington repair.
      When the 2-strand repair (2-0 Fiberwire) was compared to the 4-strand single
      Pennington repair (4-0 Fiberloop), there was no significant difference found.
      CONCLUSIONS: The suture strand configuration rather than the strict number of
      strands or the strength of the suture material yielded the maximum tensile
      strength with reduced gapping at the repair site.

PMID- 22964670
TI  - A critical review of the literature and an evidence-based approach for life
      threatening hemorrhage in maxillofacial surgery.
AB  - BACKGROUND: Life-threatening facial hemorrhage in Maxillofacial Surgery (MFS) has
      an approximate incidence of 1% in the trauma patient and in elective surgery. The
      treatment of acute life-threatening hemorrhage in MFS to prevent hypovolemic
      shock or airway obstruction forms the basis of emergency care and necessitates
      the need for further analysis given the multitude of options proposed for
      treatment. A systematic review of the literature was undertaken to formulate an
      evidence-based approach to the treatment of life-threatening hemorrhage in MFS.
      MATERIALS AND METHODS: A comprehensive search of journal articles was performed
      using PubMed and Ovid databases. Keywords and phrases used were "life threatening
      facial hemorrhage," "life threatening facial bleeding," "external carotid artery
      ligation," and "external carotid artery embolization." Our search yielded 1441
      articles. In an attempt to focus on hemorrhage exclusively from traumatic and
      operative events, articles that cited hematological disorders as the underlying
      cause of bleeding were excluded from the study. There were 40 articles which met
      the full inclusion criteria and form the basis of this systematic review. The
      articles were rated based on the level of evidence. There was 1 Level II, 21
      Level III, 12 Level IV, and 6 Level V papers. RESULT: Seven Level III evidence
      based studies noted a high association between midface injuries, particularly
      Lefort III fractures and massive oronasal hemorrhage. One Level II study, 8 Level
      III studies, and 3 Level IV studies concluded that the internal maxillary artery
      was most frequently associated with intractable posttraumatic hemorrhage. One
      Level II, 16 Level III, 3 Level IV, and 3 Level V articles cited anterior and
      posterior nasal packing and conservative measures as the first attempt to manage
      traumatic hemorrhage. Subsequently, 8 Level III studies re-enforced the
      importance of temporary reduction of facial fractures as an effective means to
      control massive hemorrhage early in the algorithm. Seven Level III studies, 4
      Level IV, and 2 Level V studies documented the importance of ligation of arteries
      as one of the absolute measures to manage facial hemorrhage, whereas 1 Level II,
      14 Level III, 2 Level IV, and 3 Level V studies alluded to embolization as the
      most reliable technique for control of the hemorrhage. In orthognathic surgery,
      the internal maxillary artery was most frequently the source of massive
      hemorrhage according to 2 Level III, 4 Level IV, and 1 Level V studies. Two Level
      III, 5 Level IV, and 1 Level V study proposed packing as the first attempt to
      tamponade the hemorrhage. Two Level IV and 1 Level V study cited pseudoaneurysm
      as a potentially life-threatening vascular complication after elective surgery.
      CONCLUSIONS: Management of facial hemorrhage should be performed in a sequential
      and consistent manner to optimize outcome. An evidence-based algorithm for
      posttraumatic and elective life-threatening hemorrhage in MFS based on this
      critical review of the literature is presented and discussed.

PMID- 22964671
TI  - Quality of life after breast reduction surgery: a 10-year retrospective analysis
      using the Breast Q questionnaire: does breast size matter?
AB  - BACKGROUND: Patient reported outcome studies are extremely valuable. We
      hypothesize that breast reduction surgery has a high satisfaction rate, and that
      body mass index (BMI), and the amount of breast tissue removed would not alter
      this outcome. The purpose of this study was to determine if there is an
      improvement in the quality of life in patients undergoing breast reduction
      surgery, and whether breast volume or patient size influences this outcome.
      METHODS: A retrospective chart review was performed on 600 consecutive patients
      at a single institution from 2000 to 2010. Patients were mailed The Breast Q
      questionnaire to complete. Demographic, surgical, and clinical data were
      collected and entered into a database. Descriptive statistical analyses were
      conducted using SAS Software version 9.1.3 with statistical significance
      determined at P<0.05. RESULTS: A total of 178 surveys were returned and included
      in our study (a response rate of 29.6%). Patient data included a mean BMI of 28.3
      (4.6) kg/m, and mean total amount of breast tissue removed of 1220.9 (665.4) g.
      The primary indications for patients having breast surgery were for symptomatic
      macromastia (85%), asymmetry (5.6%), and for cosmesis (2.5%). The Breast Q
      questionnaire demonstrated patients overwhelmingly agreed that they were
      satisfied with their breast surgery. The mean response was 2.8 with a standard
      deviation (SD) of 0.47 (where 1, disagree; 2, somewhat agree; and 3, definitely
      agree). Patient BMI and total amount of breast tissue removed had a statistically
      significant positive correlation (0.479; P<0.0001). There was no statistically
      significant difference between the amount of total breast tissue removed and
      patient response (P=0.57). CONCLUSIONS: The study supports a positive outcome
      after breast reduction surgery. Over 95% of the patients surveyed were satisfied
      and would do it again. It demonstrates the improvement of the patient's quality
      of life regardless of the amount of breast tissue removed. Furthermore, it
      suggests that the size and weight of the patient has no impact on this outcome.
      As we face new government and insurance restrictions for surgeries that have both
      cosmetic and reconstructive value, patient reported outcome studies may have an
      influence on future third-party payer.

PMID- 22964672
TI  - A targeted approach to sentinel lymph node biopsies in the parotid region for
      head and neck melanomas.
AB  - INTRODUCTION: Cutaneous melanoma is on the rise in the United States, and the
      head and neck region is the primary site in 20% of patients. Lymph node status is
      the best indicator of prognosis for melanoma. In the head and neck, sentinel
      lymph node (SLN) biopsy presents particular challenges, with the parotid region
      posing difficulties that include locating the lymph nodes, less frequent
      visualization of blue dye, and the possibility of higher morbidity because of the
      proximity of lymph nodes to important neurovascular structures. Surgical
      approaches to the SLN dissection in the parotid region are variable, and may
      include superficial or total parotidectomies. Parotid-sparing SLN biopsies for
      head and neck melanomas were evaluated to determine rates of local recurrence.
      METHODS: The charts of 301 patients from the Yale Melanoma Unit who underwent
      resection of their head and neck melanoma were reviewed. The location of the
      primary melanoma was noted, and the sentinel lymph node dissections from the
      operative reports were documented. Demographic and outcome data were recorded,
      including course of melanoma management, local recurrence, and postoperative
      course. RESULTS: Fifty-eight patients underwent SLN biopsy of lymph nodes in the
      parotid region. Parotid-sparing SLN biopsies comprised 94.8% of total surgical
      approaches for SLN biopsies in the parotid region. Of the remaining patients who
      underwent SLN biopsies in the parotid region, 5.17% had a superficial
      parotidectomy and none had a total parotidectomy. Sentinel lymph nodes were found
      in all depth layers of the parotid, and LNs were dissected out successfully
      without the need to remove the parotid in the most cases. The parotid region
      recurrence rate was 0% for SLN biopsies that either included or spared the
      parotid gland. There were no localized complications from the sentinel lymph node
      biopsies. CONCLUSIONS: The parotid-sparing SLN biopsy was performed without any
      local recurrence in the parotid region. The parotid-sparing SLN biopsy can be
      carried out in a safe, efficient manner without affecting the rate of local
      recurrence or postoperative complication. This less-invasive SLN biopsy procedure
      precludes the complications associated with parotidectomies and may reduce the
      morbidity for patients with melanomas of the head and neck.

PMID- 22964673
TI  - An analysis of leading, lagging, and coincident economic indicators in the United
      States and its relationship to the volume of plastic surgery procedures
      performed.
AB  - In plastic surgery, 2 predominant practice environments exist, namely, the
      academic setting and private practice. These 2 groups cater their practice toward
      the needs and demands of 2 very different patient populations. The goal of this
      paper is to examine well-established economic indicators and delineate their
      relationship, if any, with the volume of different plastic surgical procedures
      performed in the United States. Information from the American Society of Plastic
      Surgeons' annual reports on plastic surgery statistics was collected from the
      year 2000 through 2010 and compared to readily available and established economic
      indicators. There was a significant positive relationship with total cosmetic
      procedures and gross domestic product (GDP), GDP per capita, personal income,
      consumer price index (CPI) (all), and CPI (medical). There was a significant
      positive relationship between cosmetic surgical procedures and the issuance of
      new home permits and the average prime rate charged by banks. There was a
      significant positive relationship with cosmetic minimally invasive procedures and
      GDP, GDP per capita, personal income, CPI (all), and CPI (medical). There was a
      significant negative relationship between reconstructive procedures and GDP, GDP
      per capita, personal income, CPI (all), and CPI (medical). Cosmetic minimally
      invasive procedures seem to be decided on relatively quickly during good economic
      times. Cosmetic surgical procedures seem to be more planned and less related to
      the economic environment. The plastic surgeon may use this relationship to tailor
      the focus of his or her practice to be best situated for economic fluctuations.

PMID- 22964674
TI  - Subjective rating of cosmetic treatment with botulinum toxin type A: do existing
      measures demonstrate interobserver validity?
AB  - BACKGROUND: Throughout the literature, investigators have assessed the cosmetic
      efficacy of botulinum toxin (BT) treatment by using various subjective,
      qualitative measures, including the Facial Wrinkle Scale (FWS) and Subject Global
      Assessment (SGA). The widely used FWS and SGA attempt to quantify both the
      magnitude and duration of cosmetic outcomes as assessed by physician and patient.
      We sought to determine the interobserver validity of these scales relative to the
      level of observer experience. METHODS: Botulinum toxin injections were performed
      to cosmetic effect in 6 patients recruited as part of an institutional review
      board-approved investigation. Subjects were photographed at rest and during
      animation (raising eyebrows, frowning, and blinking) before treatment and at 1,
      2, 4 weeks, and monthly with follow-up to 6 months. Standardized digital 8"*10"
      prints were scored using the FWS by board-certified plastic surgeons (n=5),
      general surgery residents (n=3), and medical students (n=4). Photographs at each
      time point were then compared to baseline using the SGA. Statistical analysis of
      observer data was performed using SPSS v19. Cohen kappa (FWS) and Spearman rho
      (SGA) were calculated for each pairwise comparison of observer data, with a
      conservative alpha of 0.01. RESULTS: The FWS observer scores for the upper face
      overall were generally in agreement, with no negative kappa values. The
      distribution, even among members of a single group, was highly variable.
      Agreement among plastic surgeons was the greatest (kappa, 0.194-0.609). Resident
      concordance was moderate, and medical students displayed the most variable
      agreement. Spearman rho for SGA scores was much higher, with surgeons approaching
      excellent agreement (kappa, 0.443-0.992). In comparisons between members of
      different groups, agreement was unpredictable for both the FWS and SGA.
      Comparisons using scores from individual areas of the face were least concordant.
      CONCLUSIONS: The FWS and SGA represent the current standard of cosmetic outcomes
      measures; however, when subjected to scrutiny they display relatively
      unpredictable agreement even among plastic surgeons. Compared to the FWS, the SGA
      has a more acceptable user concordance, especially among plastic surgeons
      accustomed to using such scales. The interobserver variability of FWS and SGA
      scoring underlines the need to explore objective, quantitative cosmetic outcomes
      measures.

PMID- 22964675
TI  - Should surgeons use arm restraints after cleft surgery?
AB  - BACKGROUND: Most cleft surgeons require children to wear postoperative arm
      restraints although the literature suggests that there is no difference in early
      complications. The aim of this study was to determine if the use of postoperative
      arm restraints was effective in preventing early postoperative complications.
      METHODS: We reviewed 120 consecutive primary cleft surgeries in which 1 surgeon
      used arm restraints in all patients and the other surgeon did not. Demographic
      information was obtained and complications were reviewed. We compared infection,
      fistula, and dehiscence between the 2 groups. RESULTS: In 120 primary cleft
      surgeries, there was no difference in early complications in patients who were
      required to wear arm restraints versus those who were not (P<0.05). DISCUSSION:
      Arm restraints are unnecessary and may cause distress in both patients and their
      families. Eliminating arm restraints from cleft care would save the health care
      system an estimated $234,000 annually.

PMID- 22964676
TI  - Soft tissue injury management with a continuous external tissue expander.
AB  - BACKGROUND: Blast exposure is a common cause of soft tissue injury within the
      battlefield setting, with the extremities often critically involved. The
      resulting injury pattern presents with massive soft tissue defects that may be
      further complicated by varying degrees of accompanying orthopedic and peripheral
      nerve damage. To address the severe soft tissue defect, various combinations of
      advanced reconstructive methods are typically required to achieve definitive
      wound coverage. Continuous external tissue expansion has been used by our
      institution to significantly reduce wound burden and provide for definitive wound
      closure in certain blast-injured patients. METHODS: The authors present an early
      series of 14 patients who suffered massive extremity soft tissue injuries and
      were treated with an external tissue expansion system (DermaClose RC). Outcome
      measurements included time to definitive closure and method of definitive wound
      closure. A 5-patient subset of this group was prospectively analyzed to determine
      measurements including initial wound surface area (WSA), percentage reduction in
      WSA, and related complications. RESULTS: Overall time to wound coverage ranged
      from 1 to 6 days, with mean time to wound coverage being 4.4 days. Of the 14
      patients included in the series, 12 (85.7%) were able to undergo delayed primary
      closure, whereas 2 required split thickness skin grafting. In the 5-patient
      subgroup, WSA initially ranged from 20.25 to 1031.25 cm2. Mean wound size was
      262.7 cm2. Decrease in WSA ranged from 44% to 93% of the initial WSA, with mean
      decrease being 74.3% (95% confidence interval, 57.33-91.3). CONCLUSIONS: In the
      management of large complex wounds, external tissue expansion has proven to be a
      valuable adjunct in achieving definitive wound closure. It can often aid in
      successful delayed primary closure of certain soft tissue wounds, has low
      associated morbidities, and can reduce the need for more complex or morbid
      procedures when used properly. The authors propose an algorithm for the use of
      continuous external tissue expansion system to achieve effective and successful
      wound closure, while potentially reducing the need for increased donor-site
      morbidities associated with more complex or larger reconstruction measures.

PMID- 22964677
TI  - The impact of liposuction cannula size on adipocyte viability.
AB  - PURPOSE: Autologous fat transfer ("fat grafting") is widely used in cosmetic and
      reconstructive surgery, but long-term outcomes remain inconsistent. Each step in
      the transfer process can cause mechanical damage to the graft tissue. In
      particular, liposuction breaks aspirated adipose tissue into distinct globules
      and subjects it to shear forces, both of which can impact subsequent fat graft
      viability. The optimal size of the liposuction cannula for use in fat grafting is
      not known. METHODS AND TECHNIQUES: Controlled lipoaspirate samples were collected
      from adult female patients undergoing elective liposuction of the abdomen and
      flanks with uniform aspiration pressure (-25 in Hg) and either a 3- or 5-mm
      standard blunt-tip liposuction cannula. Individual grafts of 1.00+/-(0.01) gram
      were prepared and injected into the bilateral flanks of nude mice with a 14-gauge
      catheter. After six weeks, these grafts were explanted and analyzed by weight and
      histology. RESULTS: At six weeks, fat lobules in the 5-mm group retained 25% more
      weight than those in the 3-mm group [mean (SD), 0.70 (0.07) vs 0.56 (0.09) g,
      n=24/group, P<0.01). Histologic analysis revealed more intact, nucleated
      adipocytes in the 5-mm group than in the 3-mm group [4.42 (0.92) vs 3.10 (0.56)
      on a 1-5 rating scale]. The 5-mm group exhibited both less infiltrate [1.58
      (0.17) vs 3.13 (0.70)] and less fibrosis [1.67 (0.45) vs 3.13 (0.89)] than the 3
      mm group. CONCLUSIONS: In this controlled model of fat grafting with either a 5-
      or 3-mm aspiration cannula, the use of a larger aspiration cannula led to
      improved graft retention and quality. This finding has important implications for
      clinical applications of fat grafting.

PMID- 22964678
TI  - Nipple-sparing mastectomy and immediate free-flap reconstruction in the large
      ptotic breast.
AB  - Because of increased risk for nipple necrosis, many surgeons believe large ptotic
      breasts to be a relative contraindication to nipple-sparing mastectomy (NSM). A
      retrospective review was performed on 85 consecutive patients who underwent NSM
      with 141 immediate perforator free-flap breast reconstructions. We analyzed the
      subset of patients with large ptotic breasts, defined as cup size C or greater,
      sternal notch to nipple distance greater than 24 cm and grade 2 or 3 breast
      ptosis. Of the 85 patients, 19 fit the inclusion criteria. Breast cup size ranged
      from 34C to 38DDD. There was 1 case of nipple necrosis in the patient with
      previous breast radiation (5%), 1 hematoma (5%), and no flap losses. Five (26%)
      patients underwent subsequent mastopexy or breast reduction, a mean of 6.6 months
      after the primary procedure. We demonstrate that NSM and free-flap breast
      reconstruction can be safely and reliably performed in selected patients.

PMID- 22964679
TI  - Deep venous thrombosis prophylaxis in body contouring: 105 consecutive patients.
AB  - Body contouring has a higher rate of thromboembolism than traditional plastic
      surgery procedures. Although risk stratification protocols exist, few offer
      specific therapeutic guidelines for deep venous thrombosis prevention. This
      single surgeon series classifies 105 consecutive patients into low, moderate,
      high, and highest risk groups. The respective thromboembolism prevention
      treatment included pneumatic compression devices alone, postoperative low-dose
      unfractionated heparin (LDUH), preoperative and 2 doses of postoperative LDUH,
      and preoperative and postoperative LDUH/low-dose molecular weight heparin for 7
      days. Complications included 1 reoperation for bleeding. There were no clinically
      detected deep venous thromboses. In conclusion, this treatment algorithm for
      thromboembolism prevention results in a low rate of bleeding and thrombosis.
      Further studies are warranted to determine optimal timing and duration of
      chemoprophylaxis in plastic surgery patients.

PMID- 22964680
TI  - Thoracodorsal artery perforator flaps and muscle-sparing latissimus dorsi
      myocutaneous flaps for the treatment of axillary hidradenitis.
AB  - PURPOSE: The purpose of this study was to review a single surgeon's experience
      with using the thoracodorsal artery perforator (TAP) flap for coverage of
      axillary defects. METHODS: This is a retrospective review of all flaps performed
      by the senior author (D.W.L.) after excision of axillary hidradenitis between
      2004 and 2010. RESULTS: Nine TAP flaps were successfully performed, whereas 5
      muscle-sparing latissimus dorsi (MSLD) myocutaneous flaps were necessary because
      of the inability to harvest a perforator flap. Overall, this equates to a 64%
      success rate in harvesting a perforator flap. The mean sizes of the TAP and MSLD
      flaps were 75 cm (range, 32-120 cm) and 83 cm (range, 48-160 cm), respectively.
      There were 2 (14%) flaps with wound complications. One patient had recurrent
      disease requiring debridement. Another patient who underwent the largest of all
      flaps (MSLD) had donor site and recipient bed dehiscence requiring debridement
      and skin grafting. This patient also later required flap debulking and Z-plasty
      for scar contracture. DISCUSSION: Overall, TAP and MSLD flaps can be performed
      reliably for coverage of axillary defects after excision of hidradenitis.
      Although not free of complications, they do offer improved results compared to
      historic attempts at primary closure or skin grafting.

PMID- 22964681
TI  - Outcomes of delayed abdominal-based autologous reconstruction versus latissimus
      dorsi flap plus implant reconstruction in previously irradiated patients.
AB  - BACKGROUND: Local recurrence after breast conservation therapy is usually managed
      with salvage mastectomy. Multiple methods of reconstruction are possible,
      although delayed autologous reconstruction provides the most reliable results.
      METHODS: We compared complications in delayed abdominal-based [transverse rectus
      abdominis muscle (TRAM)/deep inferior epigastric perforator (DIEP)]
      reconstruction with delayed latissimus dorsi plus implant-based reconstruction in
      previously irradiated breasts. The authors reviewed 133 consecutive cases of
      delayed breast reconstructions performed in patients who had postmastectomy
      radiation therapy and reconstruction with abdominal-based methods (single-pedicle
      TRAM, supercharged pedicle TRAM, muscle-sparing TRAM free flap, DIEP flap, and
      superficial inferior epigastric artery flap) or a pedicled latissimus dorsi flap
      plus implant. Complications for donor and recipient sites were recorded including
      infection, seroma, hematoma, and partial flap loss. RESULTS: Seventy-five
      patients were reconstructed with abdominal-based flaps (37 muscle-sparing TRAMs,
      19 pedicled TRAMs, 12 DIEPs, 6 supercharged pedicled TRAMs, and 1 superficial
      inferior epigastric artery). Their median age was 50 years and mean follow-up was
      22.7 months. Three (4.0%) patients required reoperation during the same hospital
      visit for vascular compromise that resulted in 2 (2.7%) flap failures. Three
      (4.0%) patients had partial flap loss that ultimately required debridement and
      primary closure. Seventeen (22.7%) patients had minor complications including
      seroma, small hematoma, cellulitis, and abdominal bulge. Fifty-six patients were
      reconstructed with latissimus dorsi flaps plus implants. Their median age was 47
      years and mean follow-up was 32 months. Three (5.4%) patients developed
      infections resulting in implant loss. Four (7.1%) patients had partial flap loss
      that required debridement and primary closure. Thirteen (23.2%) patients had
      minor complications including seroma (12 patients) and hematoma (1 patient) that
      required drainage. Fisher exact test was used to determine statistical
      significance of complication and failure rates between the 2 types of
      reconstruction. In patients who had postmastectomy radiation therapy, those with
      abdominal-based reconstructions had fewer complications compared with latissimus
      dorsi flap plus implant reconstructions (28.0% vs 30.4%, P=0.846). Also, fewer
      reconstructions failed in patients with abdominal-based reconstruction (2.7% vs
      5.4%, P=0.650). CONCLUSIONS: Abdominal-based autologous reconstruction had fewer
      complications and fewer reconstruction failures than latissimus dorsi flap plus
      implant reconstructions in patients with postmastectomy radiation therapy in our
      series; however, these rates were not statistically significant.

PMID- 22964682
TI  - Beyond fat grafting:  what adipose tissue can teach us about the molecular
      mechanisms of human aging.
AB  - BACKGROUND: The concept of aging and the mechanisms responsible for soft tissue
      aging have become progressively more important as the world's population ages and
      demands a higher quality of life. Although molecular mechanisms of aging have
      been evaluated in model organisms, specific genomic, genetic, and epigenetic
      modifications that can be translated to normal human tissue aging have yet to be
      identified. We propose that adipose tissue is an excellent model with which to
      investigate molecular aging pathways. The goal of this study is to demonstrate
      that primary human adipose tissue can serve as a model of human aging, and
      further, can be used to detect differences in genomic transcriptional profiling
      between cell types in adipose tissue as well as between youthful and older age
      groups. METHODS: Subcutaneous adipose tissue was excised during cosmetic
      procedures from healthy patients. Adipocytes and stromal vascular fractions from
      the anterior abdomen were isolated from 3 young (26-39 years) and 3 old (52-64
      years) patients and analyzed for genome-wide transcriptional differences between
      varying ages and cell types using the Affymetrix GeneChip Human Gene Chip 1.0ST.
      RESULTS: Genes specific to adipocytes were more highly expressed in adipocytes
      than in stromal vascular fractions, validating that adipose tissue should be
      examined in a cell-specific manner. An increase in overall gene expression was
      observed among patients in the older age group, consistent with senescence
      related chromatin dysregulation. Principal components analysis revealed no clear
      delineation between age groups and a clear separation by cell type. Analysis of
      variance revealed cell type as the most significant variable in transcriptional
      differences, whereas age-related differences were a distant second. Gene Ontology
      categories of the most significantly modified genes included RNA splicing and
      mRNA metabolism, plasma membrane, and mitochondrial metabolism. CONCLUSIONS:
      Primary adipose tissue is an effective model for the study of the molecular
      mechanisms of human aging. Our findings are consistent with the hypothesis that
      epigenetic modifications play a more important role than transcriptional
      modifications in early human adipose tissue aging. Our future studies will
      examine the contribution of specific epigenetic markers to human adipose tissue
      aging and promise to advance approaches in regenerative medicine, and the
      prevention and treatment of aging.

PMID- 22964683
TI  - Anesthesia duration as a marker for surgical complications in office-based
      plastic surgery.
AB  - BACKGROUND: Office-based plastic surgery has continued to rise in the past 2
      decades with the increased demand for cosmetic surgery. Although several large
      studies have shown the safety of office-based surgery, current regulations place
      some restrictions on ambulatory office-based surgical facilities. To provide
      further evidence-based literature on the safety of office-based plastic surgery,
      we examine surgical complication rates as a function of anesthesia duration.
      METHODS: This is a retrospective review of 2595 patients who underwent office
      based plastic surgery procedures between October 2000 and January 2005. All
      patients received general anesthesia for a broad range of cosmetic surgeries. The
      primary measured outcome was minor and major surgical complications. Complication
      rates were examined as a function of anesthesia duration of less than or greater
      than 4 hours. The follow-up period was 30 days. Statistical analysis was
      completed using SPSS v.19. RESULTS: Most of the patients were female with an
      average age of 41 years. An increase in the occurrence of minor surgical
      complications such as postoperative nausea and vomiting (2.8% vs 5.7%, P=0.0175)
      and urinary retention (0.7% vs 7.6%, P<0.0001) was noted in the greater than 4
      hour anesthesia duration group. Overall, there were 66 (2.5%) patients that
      required reoperation because of surgical complications with no statistical
      difference between the 2 groups (P=0.098). The only major morbidities were 1
      pulmonary embolism (<4 hours) and 1 deep vein thrombosis (>4 hours). Five (0.19%)
      patients were admitted to the hospital during the follow-up period for surgical
      and/or medical management (3 hematomas, 1 deep vein thrombosis, and 1 pulmonary
      embolism). There were no cases of reintubation, major cardiac complications, or
      death in this series. CONCLUSIONS: Duration of general anesthesia in office-based
      plastic surgery does not seem to be an indicator of major morbidity and
      mortality. Although minor complications such as postoperative nausea and vomiting
      and urinary retention were higher in patients with anesthesia greater than 4
      hours, there was no significant increase in major complications. Change in
      surgical venue would not likely alter the outcome of the increase in minor
      complications. Therefore, anesthesia duration should not be used as a guideline
      for safety of office-based plastic surgery.

PMID- 22964684
TI  - Annual Northeastern Society of Plastic Surgeons issue of the Annals of Plastic
      Surgery.

PMID- 22964685
TI  - Evidence-based protocol for infection control in immediate implant-based breast
      reconstruction.
AB  - Immediate breast implant reconstruction has among the highest incidence of
      infections in plastic surgery. A literature search returned key articles that
      showed a significant decrease in surgical-site infections by performing nasal
      swab evaluation to treat methicillin-sensitive and methicillin-resistant
      Staphylococcus aureus before surgery with mupirocin nasal ointment and 5 days of
      chlorhexidine scrub to the surgical area. Additional Level 1 data supported the
      use of chlorhexidine-alcohol over povidone-iodine solutions for skin preparation.
      Intraoperative data on breast pocket irrigation showed the benefits of povidone
      iodine as well as a triple antibiotic solution. Nasal swabs from 120 patients
      showed no methicillin-resistant S. aureus but did identify 10 patients with
      methicillin-sensitive S. aureus, 1 with streptococcus, and 3 with gram-negative
      rods, which changed perioperative antibiotic management. On the basis of the
      previously mentioned data, an evidence-based protocol for infection control was
      developed to potentially decrease infection rates. Further cost and efficacy data
      are warranted.

PMID- 22964686
TI  - Homing distance in desert ants, Cataglyphis fortis, remains unaffected by
      disturbance of walking behaviour and visual input.
AB  - Desert ants gauge walking distance by means of a stride integrator and, to a
      minor extent, by optic flow integration. With the present experiments we attempt
      to interfere with both, stride integration and optic flow input in order to
      reveal possible interactions of the two modes of odometry and further functional
      details of the stride integrator. We tried to impair stride integration by
      amputating two of the six walking legs. Amputation of left middle and right hind
      legs had especially severe effects since it left only the right front leg in one
      of the support tripods that are alternately used in walking. We tried to impair
      optic flow input - which is used for distance estimation to a minor extent - by
      covering both ventral eye halves. These two sets of manipulations were carried
      out in combination to study possible compensatory effects, for instance, of optic
      flow input in the case of an impaired stride integrator. Unexpectedly, none of
      the manipulations we carried out had significant effects on homing performance.
      This was true with regard to homing distance estimation (as determined by the
      centres of the ants' nest searches) and homing certainty (as determined by the
      search spreads). These results corroborate the surprising robustness of odometry
      by stride integration, and they indicate that leg proprioceptive feedback is used
      for stride integration. The question of a possible interaction of optic flow
      input and stride integration remains open. 

PMID- 22964687
TI  - A case report of unusual retroperitoneal Castleman's disease in an old woman.
AB  - Castleman's disease (CD) is an uncommon disorder of the lymphoid hyperplasia. It
      is especially rare in the retroperitoneum or perirenal area. We report the case
      of a 62-year-old woman who had an abdominal mass localized above the right kidney
      in the region of the right adrenal gland found by computed tomography scan. The
      patient subsequently underwent an exploratory laparotomy. Pathological
      examination revealed retroperitoneal localized CD (LCD) of the hyaline vascular
      type. Diversity of disease sites and nonspecificity of clinical manifestations
      lead to diagnostic difficulties. Therefore, diagnosis is mainly achieved via
      lymph node biopsy or pathological examination. Like in the reported case, LCD
      usually has a good prognosis after complete resection of the lesion.

PMID- 22964689
TI  - Detection of prostate cancer by radio-frequency near-field spectroscopy in
      radical prostatectomy ex vivo specimens.
AB  - BACKGROUND: The aim of radical prostatectomy (RP) is the complete removal of the
      prostate gland with negative surgical margins. The presence of cancer at the
      surgical margin is associated with higher probability of disease progression.
      Current methods of intraoperative margin assessment are inaccurate or time
      consuming.The study goal was to evaluate the ability of a novel device (Dune
      Medical Devices) to differentiate between cancer and BPH. METHODS: A total of 49
      patients undergoing RP in four medical centers between November 2007 and May 2008
      were enrolled in this study.The device was applied to numerous intra- and extra
      capsular sites of freshly excised RP specimens. Measurement sites were accurately
      marked and analyzed histologically. The ability of the device to differentiate
      between malignant and nonmalignant sites was assessed. RESULTS: A total of 15,156
      measurements from 45 patients were analyzed. Differentiation of the intra
      capsular malignant sites from extra-capsular nonmalignant sites (bladder neck and
      apex regions) depends on the cancer feature size. Differentiation was achieved
      with sensitivity and specificity of 93.6 (95% confidence interval (CI): 88-98)
      and 94.1 (95% CI: 93-95), respectively, at feature sizes at or >0.8 mm in
      diameter. The device was able to discriminate between all intra-capsular
      malignant (with feature sizes down to a few cells) and nonmalignant measurement
      sites, with sensitivity and specificity of 80.8 (95% CI: 73-87) and 68.4 (95% CI:
      67-69), respectively. CONCLUSIONS: First results from a radio-frequency near
      field spectroscopy sensor look promising for differentiation between cancer and
      benign prostate tissue. The sensor's dimensions (radius of ~ 1 mm) and design
      enable use in open, laparoscopic and robotic RP to evaluate the surgical margins
      intraoperatively.

PMID- 22964690
TI  - Spot urine potassium as a potential screening test for aldosterone breakthrough.
AB  - BACKGROUND AND AIMS: Treatment with angiotensin converting enzyme inhibitors
      (ACEIs) or angiotensin receptor blockers (ARBs) may suppress aldosterone
      production only in the initial phase of treatment and subsequently lead to a
      rising level of aldosterone to baseline or higher. This phenomenon is described
      as aldosterone breakthrough. Apart from serial plasma aldosterone levels, there
      are no other test to identify this condition. The purpose of this study was to
      evaluate the role of spot urine potassium as a potential screening test for
      aldosterone breakthrough. MATERIALS AND METHODS: This was a cross sectional study
      involving 94 patients who were on an ACEI or ARB for a minimum duration of 40
      weeks. An aldosterone cut off value of 102 pg/ml was used to define aldosterone
      breakthrough based on a previous study. Patients with primary hyperaldosteronism,
      conditions giving rise to secondary hyperaldosteronism and those who were on
      drugs which could interfere with the renin-angiotensin-aldosterone system were
      excluded. The study patients had their blood sample analysed for renal profile,
      renin, aldosterone and urine sample analysed for urine potassium. RESULTS:
      Incidence of aldosterone breakthrough in this study was 23.4%. The median urine
      potassium was 62.0 mmol/L in the aldosterone breakthrough group compared to the
      non-breakthrough group which was 38.5 mmol/L. The urine potassium showed
      statistically significant difference between both groups (p=0.016). The
      correlation coefficient was 0.284; statistically significant (p=0.006) as the
      sample size was large (n=94). CONCLUSION: A raised urinary potassium after
      initiating treatment ith ACEI or ARB is a potential screening test for
      aldosterone breakthrough.

PMID- 22964691
TI  - Special tinted contact lens on colour-defects.
AB  - PURPOSE: The objective of this study was to determine the visual function of
      colour-deficient subjects when wearing special red tint contact lenses. MATERIALS
      AND METHODS: A total of 17 subjects with congenital colour vision deficiency (14
      deutans and 3 protans), voluntarily participated in this study. The average age
      for the subjects was 23.00 +/- 4.06 years old. Visual functions tested were
      visual acuity (LogMAR), contrast sensitivity (FACT Chart) and stereopsis (TNO and
      Howard Dolman tests). Two types of special red tint lenses were used in this
      study; Type I (light red) and Type II (dark red). RESULTS: The protans and
      deutans showed no significant changes in visual acuity and contrast sensitivity
      when wearing either type of contact lens. Stereopsis testing using the Horward
      Dolman test gave no significant changes but significant differences were seen
      using the TNO test. Stereopsis using the TNO test was significantly poorer with
      the red tinted contact lenses compared to without for both protons and deutans.
      Testing binocularly with Ishihara plates showed that 88% (n=15) of patients
      passed the test with Type I and Type II contact lenses. When D15 test was done, 3
      patients (17.6%) were 'normal' when using the Type I contact lenses and 2
      patients (11.8%) were 'normal' when using the Type II contact lenses. However,
      with FM100Hue test, most patients showed deutan responses. Total error scores
      (TES) were found to be higher with Type I and Type II contact lenses compared to
      without. CONCLUSIONS: The Type I and II special tinted contact lens used in this
      study did not cause a reduction of visual acuity and contrast sensitivity for the
      colour defects. Stereopsis was also not reduced with the Type I and Type II
      contact lenses for the colour defects except when tested with the TNO test.
      Colour vision defects became difficult to detect using the Ishihara plates but
      FM100Hue test did not show any improvement with the Type I and Type II contact
      lenses.

PMID- 22964692
TI  - [Relation of non-alcoholic hepatic steatosis to early carotid atherosclerosis in
      diet-controlled impaired glucose tolerance subjects].
AB  - AIMS: To compare carotid artery intima-media thickness values, as a reliable
      marker of early atherosclerosis, in individuals with and without nonalcoholic
      hepatic steatosis, and to evaluate whether such differences are mediate by
      metabolic syndrome variables. MATERIALS AND METHODS: Carotid intima-media
      thickness (by ultrasonography), hepatic steatosis (by ultrasonography), insulin
      resistance (by Homeostasis Model Assessment-HOMA), steatohepatitis (by histologic
      specimen) were measured in 54 non-alcoholic steatohepatitis, and 54 IGT, compared
      with 54 healthy subjects. RESULTS: Subjects with nonalcoholic steatohepatitis had
      markedly greater carotid intima-media thickness measurements (1.38+/-0.12 vs
      1.12+/-0.10 mm; p<0.001) than controls. The marked differences in carotid intima
      media thickness that were observed between the groups were little affected by
      adjustment for age, sex, body mass index, waist/hip ratio, diabetes duration,
      blood pressure, lipids. CONCLUSIONS: These results suggest that in IGT non
      smoking subjects, the significant increase of carotid intima-media thickness in
      presence of nonalcoholic steatohepatitis cannot be mediated by HOMA-estimated
      insulin resistance; thus the NAFDL and NASH can be independent features of
      metabolic syndrome and other unknown factors can be responsible to progression of
      steatosis to NAFLD and NASH.

PMID- 22964693
TI  - Evaluation of power Doppler ultrasonography for prostate biopsy in men with
      elevated serum prostate specific antigen levels.
AB  - OBJECTIVES: To evaluate power doppler ultrasonography (PDU)-directed prostate
      biopsy in patients with elevated serum prostate specific antigen (PSA) levels.
      MATERIALS AND METHODS: Men with serum total PSA levels of more than 4 ng/ml
      undergoing biopsy for the first time were included. Grey-scale transrectal
      ultrasound (TRUS) and PDU were performed. PDU signal on vascularity accumulation
      and perfusion characteristics were recorded and graded as normal or abnormal in
      the peripheral zone of the prostate. Abnormalities were defined on transverse
      image as radial or arc hypervascularities. A biopsy regime based on Vienna
      normogram was performed in all patients. RESULTS: Overall, prostate
      adenocarcinoma detection rate was 21.4% and abnormal accumulation on PDU signal
      was identified in 96.7% of those patients (p = 0.01). PDU directed prostate
      biopsies were positive in 66.7% of the patients with prostate cancer. The
      sensitivity, specificity, positive predictive value and negative predictive value
      of PDU signal alone for prostate cancer detection was 96.7%, 24.5% and 96.4%
      respectively, and PDU guided biopsies were 66.7%, 24.5%, 19.4% and 73%
      respectively. CONCLUSIONS: The high sensitivity and negative predictive value of
      PDU makes it useful as an aid for TRUS biopsy in selected patient with previous
      negative biopsies at risk of harbouring prostate cancer.

PMID- 22964694
TI  - Epithelioid sarcoma and concurrent Volkman ischaemic contracture: a case report.
AB  - Epithelioid sarcoma is a very infrequent soft tissue sarcoma involving
      predominantly distal extremities of adolescent and young adult. We hereby report
      a case of epithelioid sarcoma in a 34-year-old young adult who presented with 1
      year history of a painful left upper limb associated subsequently with warm left
      forearm swelling and a Volkman contracture. He was treated as an inflamed soft
      tissue condition of the left upper limb. A computed tomography study showed
      presence of multiple hypodense lesions mainly in the flexor compartment of the
      left arm as well at the subcutaneous tissue, which measured 1 to 1.7 cm in
      diameter. Histological examination of the left upper limb mass showed nodular
      proliferation of epithelioid tumour cells and some with rhabdoid features
      surrounding a central zone of necrosis and was diagnosed as epithelioid sarcoma.
      Concurrent presence of epithelioid sarcoma and Volkman ischaemic contracture are
      rarely seen in clinical practice. The present case highlights the importance of
      the histology which can be confused with other types of sarcoma or chronic
      granuloma and even missed at times thereby causing diagnostic problems.

PMID- 22964695
TI  - Neuroendocrine lung cancer presenting as a breast lump.
AB  - We report the case of a 54-year-old woman presenting to our attention for a
      palpable breast lump. The mammographic examination showed multiple round/oval
      areas of increased opacity spread on both breasts. The ultrasonographic
      examination showed multiple hypo-anechoic nodularities without retro-tumor
      acoustic shadowing. The mammo/ultrasonographic findings were worthy of
      histological analysis, thus we performed a ultrasound (US)-guided core-biopsy,
      obtaining a histological diagnosis of neuroendocrine carcinoma, probably
      originating from the lungs. The subsequent whole body CT scan, performed to
      search the primary neoplasm, put in evidence a neoplasm in the left lung,
      involving the pulmonary hilum, and infiltrating the bronchial branches. Moreover,
      there were multiple secondary lesions involving adrenal glands, brain and bowel.
      A review of the literature confirmed that breast lumps may be the first
      manifestation of a metastatic disease.

PMID- 22964696
TI  - [Atypical onset cryoglobulinemia: case report].
AB  - Cryoglobulinemia is a disease mediated by antibodies with the property to
      precipitate at temperatures below 37 degrees C. It can be distinguished into a
      primitive form (also referred to as 'essential mixed cryoglobulinemia'), and a
      secondary form. In the essential mixed variant a key role is played by HCV
      infection. The pathogenesis of mixed cryoglobulinemia is mediated by immune
      complexes that are the most important cause of the vasculitic phenomena, typical
      of the disease. However, the severity of the clinical manifestations is not
      always related to the serum levels of cryoglobulins and immune complexes. In our
      case report, a 46-year old man came to our observation with asymmetric diffuse
      and invalidating arthralgies, with both substitutive and additive behaviour,
      located at pelvic girdle, inferior limbs and elbows, associated to skin lesion
      vascultis-like. The remote pathological anamnesis was characterized by a previous
      surgically treated non-Hodgkin lymphoma, and HCV infection. Despite several
      attempts were done, it was not possible to reveal cryoglobulins, nor reumatoid
      factor in the serum. Cryoglobulins resulted positive only after the third day of
      hospitalization, along with a new fever attack and a worsening of the vasculitic
      manifestations. In conclusion, this case demonstrated that cryoglobulinemia can
      occur with a totally atypical sequence of clinical manifestations which can be
      present before and in absence of the typical laboratory proofs.

PMID- 22964697
TI  - Unilateral anomalous antebrachial vasculature--a clinico-embryological insight.
AB  - OBJECTIVES: An important and frequently reported arterial variant of the upper
      extremity is the superficial ulnar artery (SUA). Although SUA is not an uncommon
      variation, its presence should be detected timely as any surgical procedure in
      this region could put this unnaturally present superficial vessel to risk.
      Therefore, we sought to report this anomaly relating to the brachial arterial
      branching pattern. MATERIALS AND METHODS: Through the course of a usual
      instructive gross anatomy class an arterial variant of the brachial artery was
      noted. A scrupulous dissection was carried out and the specimen photographed.
      RESULTS: The present study reports the unilateral presence of abnormal branching
      pattern and disposition of antebrachial blood vessels. The brachial artery is
      seen to branch off into superficial ulnar artery (SUA) and usual radial artery.
      Interestingly, common interosseous artery (CIA) springs from the radial artery
      instead of the ulnar artery which is the usual case. CONCLUSIONS: Simple
      procedures such as venepuncture and intra arterial injections may become
      cumbersome and complication prone. The study is a humble attempt to caution the
      radiologists before interpreting angiographic films and the surgeons before
      performing reconstructions in this region.

PMID- 22964698
TI  - [Ranolazine in the treatment of chronic stable angina].
AB  - Coronary artery disease is the leading cause of death in Europe and in the US and
      angina is the most common symptom associated with stable coronary artery disease.
      Despite receiving optimal antianginal therapy, based on agents such as beta
      blockers, calcium channel antagonists and nitrates, many patients continue to
      experience angina. Furthermore, the administration of these drugs is limited by
      adverse effects such as bradycardia or hypotension. Ranolazine is a new
      antianginal agent, recently approved as add-on therapy in patients with stable
      angina. This review will focus on its mechanism of action, tolerability,
      highlighting the clinical benefit coming from its use.

PMID- 22964699
TI  - Role of dopaminergic receptors in the human dura mater in the pathogenesis of
      headache.
AB  - AIMS: We hypothesize that dopaminergic receptors of dura mater may play a
      possible role in headache. MATERIALS AND METHODS: The dopaminergic receptors of
      cranial dura mater in man were studied by examining several dural zones
      (vascular, peri-vascular, inter-vascular) in different brain regions (basal,
      calvarial, tentorial, occipital, frontal, parietal, temporal). RESULTS: Our
      results demonstrate that dopaminergic receptors are present in human cranial dura
      mater and that these receptors show a specific morphological location. There are
      more dural dopaminergic receptors in the basal region than in the calvarial one.
      Moreover, these receptors are more abundant in the vascular and perivascular
      dural zone than in the intervascular one. CONCLUSIONS: The location of
      dopaminergic receptors in the dura mater may represent an important factor in the
      pathogenesis of headache. Further studies will be necessary in order to determine
      the role of dopaminergic system in this disease.

PMID- 22964700
TI  - [Obesity and arterial hypertension in children: current calamity].
AB  - OBJECTIVES: A study was carried out on students of a middle school with a medium
      high social level in a southern zone of Rome, to assess the current situation
      regarding obesity and arterial hypertension in subjects with a parental
      environment favouring correct eating habits. MATERIALS AND METHODS: We considered
      693 students, mean age 11.2 + 0.6. Hypertension was defined according to blood
      pressure (BP) tables for children and adolescents of the NIH - Fourth Report
      (systolic and diastolic BP >95th percentile for age and sex). Overweight and
      obesity were determined according to the International Obesity Task Force.
      Dietary habits and life-style were investigated by specific questionnaires.
      RESULTS: The prevalence of overweight and obesity was respectively 23.1% and 3.3%
      of the subjects studied. Moreover, 5.2% of them showed BP values between 90th and
      95th percentile and 7.8% was hypertensive. Food habits of the current students
      were fairly correct, favouring the Mediterranean diet and with the proper number
      of daily meals. DISCUSSION: A justification for the high number of hypertensive
      could be due to the elevated consumption of salt added to food (60% of young
      people), the elevated frequency of those who often eat fast food (43%) and a
      family history of hypertension in the parents (24%). Only 24.5% of males and
      22.9% of females used to practice physical activity; whereas 40% of males and 41%
      of females used to spend more than 3 hours a day in front of the TV and/or
      computer.

PMID- 22964701
TI  - Evaluation of compliance to telehomecare (THC) in a group of patients with cystic
      fibrosis (CF) in a period of 2 years.
AB  - OBJECTIVES: In the present study, we examined data related to adherence to
      telemonitoring in our CF patients followed at home for a period of 2 years, in
      the aim to improve the follow-up in terms of efficiency and appropriateness.
      MATERIALS AND METHODS: We kept electronic records of transmissions, in
      spreadsheet format. For each transmission, the main parameters and any action
      taken were collected. We carried out automatically a monthly summary of
      activities, a monthly average percentage of adherence to prescribed frequency of
      transmissions, monitored the contacts and phone calls. RESULTS: We received in
      the period from February 15, 2010 to February 15, 2012 overall 1364 transmissions
      in 515 days (1817 spirometry, 414 nocturnal pulse-oximetry and 398 questionnaires
      on symptoms) The average compliance in the reporting period was 10,16%, with an
      increasing trend. CONCLUSIONS: The improvement of outcome in FC necessarily
      passes through an improvement of the adherence to treatment. More psychological
      and behavioural studies are needed in order to gradually remove the obstacles
      which still prevent a further improvement in long-term outcome.

PMID- 22964702
TI  - Optical devices in highly myopic eyes with low vision: a prospective study.
AB  - AIMS: To compare, in relation to the cause of visual impairment, the possibility
      of rehabilitation, the corrective systems already in use and the finally
      prescribed optical devices in highly myopic patients with low vision. Some
      considerations about the rehabilitation of these subjects, especially in relation
      to their different pathologies, have also been made. MATERIALS AND METHODS: 25
      highly myopic subjects were enrolled. We evaluated both visual acuity and retinal
      sensitivity by Scanning Laser Ophthalmoscope (SLO) microperimetry. RESULTS: 20
      patients (80%) were rehabilitated by means of monocular optical devices while
      five patients (20%) were rehabilitated binocularly. We found a good correlation
      between visual acuity and retinal sensitivity only when the macular pathology did
      not induce large areas of chorioretinal atrophy that cause lack of stabilization
      of the preferential retinal locus. In fact, the best results in reading and
      performing daily visual tasks were obtained by maximizing the residual vision in
      patients with retinal sensitivity greater than 10 dB. A well circumscribed area
      of absolute scotoma with a defined new retinal fixation locus could be considered
      as a positive predictive factor for the final rehabilitation process. DISCUSSION:
      A more careful evaluation of visual acuity, retinal sensitivity and preferential
      fixation locus is necessary in order to prescribe the best optical devices to
      patients with low vision, thus reducing the impact of the disability on their
      daily life.

PMID- 22964703
TI  - A pilot study of the effect of pantothenic acid in the treatment of post
      operative ileus: results from an orthopedic surgical department.
AB  - OBJECTIVES: Post-operative ileus can also occur in other types of surgery not
      strictly related to abdomen. The objective of this study was to investigate the
      efficacy of pantothenic acid administration to stimulate intestinal peristalsis
      in case of post-operative ileus and estimate the most effective dose. This
      vitamin can be used for the treatment of chronic atonic intestine or for chronic
      constipation, but therapeutic indications are not precise in these conditions.
      PATIENTS AND METHODS: This pilot study has used patients divided in groups
      treated in post-operative period with physiological solution for patients in
      control group (Placebo) and Dexpantenolo, which is a derivative in alcohol of
      pantothenic acid, for all the actively treated patients. The treatments were
      administered intravenously during the second and third post-operative day,
      according to the treatment schedule. RESULTS: 60 patients were recruited and they
      were allocated to five treatment groups or one control group. For males, the
      median time of the first bowel evacuation was 90 hours while for females the
      median time was 84 hours (p=0.891). For patients who received a spinal
      anesthetic, the median time was 72 hours, while for those who received a
      peridural anesthetic the median time was 96 hours (p=0.571). Between six
      treatment groups, instead, there is a significant difference between the median
      times from the operation to the first bowel evacuation (p<0.001). Linear
      regression model obtained using as outcome evacuation hours after surgery show
      that only variable which significantly affects time between operation and the
      first bowel evacuation is treatment dose (Beta = -0.868, p<0.001). DISCUSSION:
      This study would seem to indicate that pantothenic acid is effective for
      treatment of post-operative intestinal ileus; there is a dose response
      relationship between pantothenic acid and the decreasing time from surgical
      operation to first bowel evacuation. However, this study is preliminary; further
      studies are necessary, preferably randomized and with a larger number of
      patients.

PMID- 22964704
TI  - Systemic contact dermatitis (SCD) due to dietary nickel.
AB  - Systemic contact dermatitis (SCD) can be caused by nickel in sensitized subjects.
      Nickel allergy is commonly characterized by localized reactions ensuring
      cutaneous exposure to this element. Systemic reactions can occur after dietary
      nickel ingestion. We report a case of a woman with Systemic Contact Dermatitis
      due to nickel.

PMID- 22964705
TI  - Ictero-haemorraghic leptospirosis with pulmonary involvement and acute renal
      failure: case report.
AB  - Leptospirosis is a spirochetal zoonosis with a worldwide distribution affecting
      both animals and humans. These are infected only occasionally by direct contact
      with infected animals or through contaminated water and soil. Generally, this
      disease is commonly found in tropical regions. Infected patients usually present
      with non-specific features. In fact, the clinical manifestations of leptospirosis
      are variable, ranging from occult infection to Weil's disease with fatal
      complications. Often the disease remains underdiagnosed due to the broad spectrum
      of signs and symptoms. Here we are reporting a case of a woman with an ictero
      haemorraghic leptospirosis complicated by acute renal failure and pulmonary
      involvement that received intensive care unit support including intubation and
      ventilation and promptly resolved with appropriate therapy.

PMID- 22964706
TI  - [Aware and cooperative reduction].
AB  - The aim of this work is to address the question of reduction in the scientific
      method, to evaluate its legitimacy as well as its pro and contra from an
      epistemological point of view. In the first paragraph we classify some kinds of
      reductionism, analysing their presuppositions and epistemological status and
      showing some examples of scientific reduction. The presentation includes a
      classificatory table that shows some of the different forms of biological
      reductionism. In the second paragraph we study the epistemology of science
      starting from its modern beginning: the Vienna Circle, focusing on the meaning of
      methodological reductionism. What did it mean for science to define itself mainly
      as method, which effects did this new concept of science have on methodology and
      what kind of problems did this movement bring about. In the third paragraph we
      examine the reactions triggered by methodological reductionism, we analyze the
      theoretical consistency of these answers, trying to offer a balanced view. We
      show how complexity can be seen as a paradigm of the anti-reductionism effort,
      and we study its epistemological basis. In the fourth paragraph we outline our
      operative proposal: the reduction that is both aware and cooperative. We point
      out the main reasons why science cannot avoid being reductive in some way, and
      therefore how we need to deal with this feature in order to prevent it to
      degenerate into reductionism. We show some examples of this new proposal taken
      from the practical realm and from literature, where it is possible to discern the
      spirit of this alternative methodology.

PMID- 22964707
TI  - [Medical English and legal English: similarities and differences between two
      specialist languages].
AB  - The comparative evaluation of specialist languages has a growing importance
      nowadays. The medical lexicon is characterized by a notable terminological
      richness both in Italian and in English, and the same is true for legal English,
      which has included, through time, a number of terms deriving from Latin and
      French. This scientific contribution highlights some features of medical
      scientific English and legal English, pointing out certain similarities and the
      differences between the two. Furthermore, with reference to the differences, a
      selection of terms with the same orthographical form but with very different
      lexical meanings is here presented.

PMID- 22964708
TI  - [Proximal femur fractures in elderly patients: the influence of comorbidity on
      prognosis in the short, medium and long term].
AB  - INTRODUCTION: Our study aims to assess post-intervention and pre-operative
      mortality in patients admitted to our institute diagnosed with a fractured
      proximal femur. The influence of comorbidity on prognosis in the short (1 month),
      medium (3 month) and long term (6 month) was assessed between July 2006 and July
      2009. MATERIALS AND METHODS: The 238 patients (85 men and 153 women), between 65-
      and 99-year-old, were followed-up as outpatients and by telephone for 1 year to
      monitor the state of persistence in life or eventually the date of death. The
      comorbidity parameters considered were: sex, age, ASA class of anesthetic risk,
      fracture location and type of surgical treatment used, the number of previous
      associated diseases and the presence/absence of cognitive impairment on
      admission. RESULTS: The data obtained, in comparison with that of the general
      population in the Lazio region (ISTAT table), showed. Higher mortality rate in
      men than women, high mortality rate for patients with cognitive impairment at
      admission (50%), mortality over twice as high in patients belonging to ASA
      classes III and IV than in patients belonging to the lower categories. By
      observing the time between surgery and death it was also evident that the first 6
      month period was the most critical; furthermore, 45.45% of deaths occurred within
      the first 60 days. CONCLUSIONS: Identifying the causes that influence the
      mortality of our patients and being able to quantify the relevance in subsequent
      death enables us to improve the care for the risk, strengthen the therapeutic
      choices based on new evidence, and especially lay the groundwork for the
      development of new treatment protocols, useful for clinical and forensing
      decision-making.

PMID- 22964709
TI  - EML4-ALK rearrangement and its clinical significance in Chinese patients with
      advanced non-small cell lung cancer.
AB  - OBJECTIVE: To identify the clinicopathological characteristics and clinical
      outcomes of Chinese patients with non-small cell lung cancer (NSCLC) and to
      investigate possible associations of NSCLC with echinoderm microtubule-associated
      protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) and epidermal growth
      factor receptor (EGFR) mutations. METHODS: Patients with stage IV NSCLC were
      screened for EML4-ALK rearrangement and EGFR mutations at the Peking University
      Cancer Hospital. EML4-ALK was identified using fluorescent in situ hybridization
      and confirmed by immunohistochemistry. EGFR mutations were determined using
      denaturing high-performance liquid chromatography. RESULTS: The incidence of EML4
      ALK was 9.7% (11/113). Patients with EML4-ALK were more likely to present the
      EGFR wild type (WT; p = 0.033). Response to EGFR-tyrosine kinase inhibitor (TKI)
      was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3
      vs. 46.9%, p = 0.451), but progression-free survival (PFS) was inferior compared
      to those with EGFR mutation (2.1 vs. 8.8 months, p = 0.032), and similar to
      patients with WT/nonrearrangement (2.1 vs. 2.2 months, p = 0.696; and general p =
      0.023 between the three cohorts). Moreover, 2 patients with concurrent EML4-ALK
      and EGFR mutations had superior PFS after EGFR-TKI compared to patients with
      single EML4-ALK rearrangement. CONCLUSIONS: Patients with EML4-ALK conferred
      similar objective response rates after EGFR-TKI although inferior PFS compared to
      those with EGFR mutation. Coexistence of EML4-ALK and EGFR mutation might
      represent a separate NSCLC genotype.

PMID- 22964710
TI  - The dawn of angiogenesis modeling: regenerating vasculature from human
      pluripotent stem cells.
AB  - Efficient generation of functional human vascular endothelial cells and smooth
      muscle cells from pluripotent stem cells is an extensively studied topic and of
      great interest in the stem cell field. Though thought to be technically complex
      and difficult, substantial progress has been made towards this direction. Here we
      aim to summarize and discuss the most recent advances in this topic and their
      future perspective in research and clinic.

PMID- 22964711
TI  - Human Stn1 protects telomere integrity by promoting efficient lagging-strand
      synthesis at telomeres and mediating C-strand fill-in.
AB  - Telomere maintenance is critical for genome stability. The newly-identified
      Ctc1/Stn1/Ten1 complex is important for telomere maintenance, though its precise
      role is unclear. We report here that depletion of hStn1 induces catastrophic
      telomere shortening, DNA damage response, and early senescence in human somatic
      cells. These phenotypes are likely due to the essential role of hStn1 in
      promoting efficient replication of lagging-strand telomeric DNA. Downregulation
      of hStn1 accumulates single-stranded G-rich DNA specifically at lagging-strand
      telomeres, increases telomere fragility, hinders telomere DNA synthesis, as well
      as delays and compromises telomeric C-strand synthesis. We further show that
      hStn1 deficiency leads to persistent and elevated association of DNA polymerase
      alpha (polalpha) to telomeres, suggesting that hStn1 may modulate the DNA
      synthesis activity of polalpha rather than controlling the loading of polalpha to
      telomeres. Additionally, our data suggest that hStn1 is unlikely to be part of
      the telomere capping complex. We propose that the hStn1 assists DNA polymerases
      to efficiently duplicate lagging-strand telomeres in order to achieve complete
      synthesis of telomeric DNA, therefore preventing rapid telomere loss.

PMID- 22964712
TI  - Crystal structure of IFIT2 (ISG54) predicts functional properties of IFITs.
AB  - Interferon carries out its cellular effects, including its antiviral effects, by
      inducing the synthesis of many new proteins, amongst which is the IFIT (ISG56)
      family of proteins. The first crystal structure of an IFIT, reported by Yang et
      al., revealed several functional properties of the protein that may help us to
      better understand the biological functions of these proteins.

PMID- 22964713
TI  - ISG15 regulates IFN-gamma immunity in human mycobacterial disease.
AB  - Interferon-gamma (IFN-gamma) is crucial for immunity against different pathogens
      due to its broad effects on the multiple arms of the immune system. The
      regulation of IFN-gamma immunity is of extensive interest to research as well as
      practical activity for drug discovery. New evidence supports previous findings
      that ubiquitin-like protein ISG15 acts as an extracellular cytokine and promotes
      IFN-gamma production, providing intriguing insights of the importance of ISG15
      into the control of human mycobacterial disease.

PMID- 22964714
TI  - Occupational exposure assessment of magnetic fields generated by induction
      heating equipment-the role of spatial averaging.
AB  - Induction heating equipment is a source of strong and nonhomogeneous magnetic
      fields, which can exceed occupational reference levels. We investigated a case of
      an induction tempering tunnel furnace. Measurements of the emitted magnetic flux
      density (B) were performed during its operation and used to validate a numerical
      model of the furnace. This model was used to compute the values of B and the
      induced in situ electric field (E) for 15 different body positions relative to
      the source. For each body position, the computed B values were used to determine
      their maximum and average values, using six spatial averaging schemes (9-285
      averaging points) and two averaging algorithms (arithmetic mean and quadratic
      mean). Maximum and average B values were compared to the ICNIRP reference level,
      and E values to the ICNIRP basic restriction. Our results show that in
      nonhomogeneous fields, the maximum B is an overly conservative predictor of
      overexposure, as it yields many false positives. The average B yielded fewer
      false positives, but as the number of averaging points increased, false negatives
      emerged. The most reliable averaging schemes were obtained for averaging over the
      torso with quadratic averaging, with no false negatives even for the maximum
      number of averaging points investigated.

PMID- 22964715
TI  - A clinimetric evaluation of allostatic overload in the general population.

PMID- 22964716
TI  - Combined rifampicin and ursodeoxycholic acid treatment does not amplify
      rifampicin effects on hepatic detoxification and transport systems in humans.
AB  - BACKGROUND: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) were found to
      stimulate different but complementary hepatobiliary detoxification pathways in
      gallstone patients. AIM: To study whether single drug effects are sustained or
      even enhanced by combination of both drugs and whether possible effects are
      mediated by circulating fibroblast growth factor 19 (FGF19), which has recently
      been identified as a master regulator of bile acid biosynthesis. METHODS: 20
      patients scheduled for laparoscopic cholecystectomy were randomized to a
      combination of UDCA (1 g/day during 3 weeks before surgery) and RIFA (600 mg/day
      during 1 week before surgery), or no treatment. Routine biochemistry, lipids,
      bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one, C-4) and FGF19 were
      measured in serum. Bile acids were analyzed in serum and bile. A wedge liver
      biopsy was taken for determination of expression of hepatobiliary ABC
      transporters on mRNA and protein levels and of enzymes and regulatory
      transcription factors involved in the metabolism of biliary compounds on mRNA
      levels. RESULTS: Combination treatment with both RIFA and UDCA significantly
      stimulated bile acid and bilirubin detoxification (CYP3A4, p < 0.001),
      conjugation (UGT1A1, p < 0.001) and elimination (MRP2, p < 0.05), as well as bile
      acid synthesis (p < 0.05), as compared to untreated controls. Notably, serum
      FGF19 levels in RIFA- and UDCA-treated patients did not differ from controls.
      CONCLUSION: Combined treatment with RIFA and UDCA preserves the previously
      observed beneficial effects of single treatment with RIFA, including stimulation
      of bile acid synthesis. Most notably, the latter effect in humans is not mediated
      by FGF19.

PMID- 22964717
TI  - Renal primitive malignant tumor with endocrine activity.
AB  - OBJECTIVE: To report a hypertensive and systematically pigmented female with
      primitive neuroectodermal tumors. CLINICAL PRESENTATION AND INTERVENTION: A
      female patient presented with a complaint of right flank pain. She had a right
      renal space-occupying lesion, underwent right radical nephrectomy, and returned
      to normotensive postoperatively. The pathological examination identified typical
      primitive neuroectodermal tumor histology. During a 60-month follow-up period,
      she remained normotensive and demonstrated normal renal and adrenal functions.
      CONCLUSION: Early diagnosis and definitive surgery led to the patient's long-term
      survival.

PMID- 22964718
TI  - Geochemistry and environmental assessment of major and trace elements in the
      surface sediments of the Wei River, China.
AB  - The development of western China in the past decade has led to increased
      discharges of wastewater and river pollution. The Wei River is the largest
      tributary of the Huang He River, but its geochemistry has not been thoroughly
      investigated. Sixty-three bed-surface sediment samples were collected from the
      Wei and analyzed for 24 elements by WDXRF; objectives for the study were to
      investigate the geochemical properties of the sediments; identify sources, and
      assess pollution levels and environmental risks. Major and trace element
      concentrations were comparable with those in other large rivers in China, but
      potentially hazardous trace elements (PHTEs) were lower than in the Yangzi or
      Pearl Rivers; most likely due to dilution of contaminants by the large sand
      inflows into the Wei and a lower level of industrialization. Nonetheless,
      pollution and risk analyses demonstrate slight contamination of Cr, Mn, Nb, Ni
      and Zn, moderate contamination of Cu and Pb, and strong contamination of As at
      some locations. Adverse biological effects from Ni and Cu are possible and are
      likely from As. Statistical and spatial analyses indicate that agriculture runoff
      and industrial wastewater discharge contribute to the contamination of this
      river. A comprehensive environmental management strategy, realistic national
      standards for wastewater discharge, and rigid enforcement are needed to address
      river pollution in China.

PMID- 22964719
TI  - HTLV-1 and -2 infections among 10 indigenous groups in the Peruvian Amazon.
AB  - Infections with HTLV-1 and -2 were detected in 12 (1.9%) and 6 (0.9%) indigenous
      individuals living in 27 Amazonian villages in Peru. All infections occurred in
      Shipibo-Konibo people. HTLV was more common among participants living in villages
      distant from larger port cities and women with non-monogamous sexual partners.

PMID- 22964720
TI  - Rapid identification of Chikungunya and Dengue virus by a real-time reverse
      transcription-loop-mediated isothermal amplification method.
AB  - Both Chikungunya and Dengue virus belong to the acute arthropod-borne viruses.
      Because of the lack of specific symptoms, it is difficult to distinguish the two
      infections based on clinical manifestations. To identify and quantitatively
      detect Chikungunya and Dengue viruses, a real-time accelerated reverse
      transcription-loop-mediated isothermal amplification (RT-LAMP) platform was
      developed, and 26-confirmed RNA samples, 42 suspects, and 18 healthy serum
      samples were evaluated by the method. The RT-polymerase chain reaction (PCR) and
      cDNA sequencing were used as references. The results showed that it could
      identify the Chikungunya and Dengue virus RNA correctly in all antibody-positive
      samples within 1 hour, without any cross-reactions. The virus load of the
      positive samples was quantitatively detected with a turbidimeter. The sensitivity
      was 100% and specificity was 95.25%. The findings indicate that the RT-LAMP is an
      effective method for rapid quantity detection of Chikungunya virus and Dengue
      virus in serum samples with convenient operation, high specificity, and high
      sensitivity.

PMID- 22964721
TI  - Pooled testing for effective estimation of the prevalence of Schistosoma mansoni.
AB  - Rapid and accurate identification of the prevalence of schistosomiasis is key for
      control and eradication of this devastating disease. The current screening
      standard for intestinal schistosomiasis is the Katz-Kato method, which look for
      eggs on slides of fecal matter. Although work has been done to estimate
      prevalence using the number of eggs on a slide, the procedure is much faster if
      the laboratory only reports the presence or absence of eggs on each slide. To
      further help reduce screening costs while maintaining accuracy, we propose a
      pooled method for estimating prevalence. We compare it to the standard
      individualed method, investigating differences in efficiency, measured by the
      number of slides read, and accuracy, measured by mean square error of estimation.
      Complication is introduced by the unknown and varying sensitivity of the
      procedure with population prevalence. The DeVlas model for the worm and egg
      distributions in the population describes how test sensitivity increases with age
      of the epidemic, as prevalence and intensity of infection increase, making the
      problem fundamentally different from earlier work in pooling. Previous literature
      discusses varying sensitivity with the number of positive samples within a pool,
      known as the "dilution effect." We model both the dilution effect and varying
      sensitivity with population prevalence. For model parameter values suited to
      younger age groups, the pooled method has less than half the mean square error of
      the individualed method. Thus, we can use half as many slides while maintaining
      accuracy. Such savings might encourage more frequent measurements in regions
      where schistosomiasis is a serious but neglected problem.

PMID- 22964722
TI  - Empyema caused by Aeromonas species in Taiwan.
AB  - Strains of Aeromonas species are prevalent bacteria in coastal areas of southern
      Taiwan. Aeromonad is known as a cause of epidemic diarrheal disease, and the most
      common clinical manifestation is acute gastroenteritis. Extra-intestinal
      infections by Aeromonas species, such as pleural cavity, are rare. Herein, we
      described the six patients who developed Aeromonas spp.-related empyema, and was
      successfully treated with antimicrobial agent and drainage.

PMID- 22964724
TI  - Molecular switches at surfaces.

PMID- 22964723
TI  - Frequency of reexposure to Vibrio cholerae O1 evaluated by subsequent vibriocidal
      titer rise after an episode of severe cholera in a highly endemic area in
      Bangladesh.
AB  - Vibriocidal antibody is a marker of recent exposure to Vibrio cholerae O1
      infection. We examined vibriocidal titers for 1 year after an episode of severe
      cholera in patients in Dhaka, Bangladesh; 16 of 53 (30%) patients had a fourfold
      or greater increase in vibriocidal titer between 6 and 12 months after an episode
      of severe cholera, suggesting reexposure to the organism. Among patients with
      rises in titers during follow-up, the patients initially infected with serotype
      Ogawa had earlier rises in titer than the patients initially infected with
      serotype Inaba. These data and others suggest that an episode of severe cholera
      protects against symptomatic disease for several years, but reexposure to the
      organism occurs frequently in an endemic area, with immunological boosts
      beginning as early as 6 months after severe disease. Repeated exposures to V.
      cholerae in endemic areas may be a necessary component for long-lasting
      protection against severe disease.

PMID- 22964725
TI  - Variation in risk-adjusted hospital readmission after treatment of appendicitis
      at 38 children's hospitals: an opportunity for collaborative quality improvement.
AB  - OBJECTIVES: To identify risk factors associated with readmission for children
      treated with appendicitis, and to characterize variation in risk-adjusted
      readmission rates between children's hospitals. BACKGROUND DATA: Hospital
      readmission has been increasingly targeted as a marker for quality of care, yet
      little is known regarding risk factors associated with readmission or the degree
      of performance variation that exists between hospitals for this cohort of
      patients. METHODS: Retrospective cohort study of 47,866 patients treated at 38
      children's hospitals (2006-2010). Multivariate regression was used to examine and
      adjust for the influence of risk factors on 30-day readmission rates. Hospitals
      were considered performance outliers if their readmission rate and 95% confidence
      interval (CI) did not include the overall rate. RESULTS: Factors associated with
      readmission included disease severity [high vs. low: odds ratio (OR) 4.57, 95%
      CI: 3.72-5.60; moderate vs. low: OR 2.29, 95% CI: 2.00-2.61] and insurance status
      (public vs. private: OR 1.14, 95% CI: 1.0-1.29). After adjustment for these
      factors, the relative decile-based performance rankings changed for 17 (45%) of
      the 38 hospitals and six (16%) hospitals changed the outlier status based on
      their standardized readmission rates. A 3.8-fold variation in standardized
      readmission rates was found across the 38 hospitals after adjustment (overall
      rate: 8.9%, range: 4.1%-15.4%, P < 0.0001), and 24 (63%) hospitals were
      identified as outliers (12 low performers and 12 high performers). CONCLUSION:
      Significant variation in risk-adjusted readmission rates exists among children's
      hospitals after treatment of appendicitis, and outliers can be identified at both
      ends of the performance spectrum. These findings may have important implications
      for the identification and dissemination of "best practices" from exemplar
      hospitals.

PMID- 22964726
TI  - Striving for work-life balance: effect of marriage and children on the experience
      of 4402 US general surgery residents.
AB  - OBJECTIVE: To determine how marital status and having children impact US general
      surgical residents' attitudes toward training and personal life. BACKGROUND:
      There is a paucity of research describing how family and children affect the
      experience of general surgery residents. METHODS: Cross-sectional survey
      involving all US categorical general surgery residents. Responses were evaluated
      by resident/program characteristics. Statistical analysis included the chi test
      and hierarchical logistic regression modeling. RESULTS: A total of 4402 residents
      were included (82.4% response rate) and categorized as married, single, or other
      (separated/divorced/widowed). Men were more likely to be married (57.8% vs 37.9%,
      P < 0.001) and have children (31.5% vs 12.0%, P < 0.001). Married residents were
      most likely to look forward to work (P < 0.001), and report happiness at work (P
      < 0.001) and a good program fit (P < 0.001). "Other" residents most frequently
      felt that work hours caused strain on family life (P < 0.001). Residents with
      children more frequently looked forward to work (P = 0.001), were happy at work
      (P = 0.001), and reported a good program fit (P = 0.034), but had strain on
      family life (P < 0.001), and worried about future finances (P = 0.005). On
      hierarchical logistic regression modeling, having children was predictive of a
      resident looking forward to work [odds ratio (OR): 1.22, P = 0.035], yet feeling
      that work caused family strain (OR: 1.66, P < 0.001); being single was associated
      with less strain (OR: 0.72, P < 0.001). The female gender was negatively
      associated with looking forward to work (OR: 0.81, P = 0.007). CONCLUSIONS:
      Residents who were married or parents reported greater satisfaction and work-life
      conflict. The complex effects of family on surgical residents should inform
      programs to target support mechanisms for their trainees.

PMID- 22964727
TI  - Fat necrosis generates proinflammatory halogenated lipids during acute
      pancreatitis.
AB  - OBJECTIVE: To evaluate the generation of halogenated fatty acids in the areas of
      fat necrosis during acute pancreatitis and to evaluate the effects of these
      molecules on the ensuing inflammatory process. BACKGROUND: Lipid mediators
      derived from adipose tissue have been implicated in the progression of acute
      pancreatitis, although their precise role remains unknown. METHODS: Acute
      pancreatitis was induced in rats by intraductal infusion of 3.5% sodium
      taurocholate. Fatty acid chlorohydrins (FA-Cl) were measured in adipose tissue,
      ascitic fluid, and plasma by mass spectrometry. Chlorohydrins were also instilled
      in the rats' peritoneal cavity, and their effects on peritoneal macrophages
      activation and in systemic inflammation were evaluated. Finally, they have also
      been measured in plasma from human patients with acute pancreatitis. RESULTS:
      Induced acute pancreatitis results in a substantial release not only of free
      fatty acids but also of the chlorohydrins of both oleic and linoleic acids from
      adipose tissue. In plasma, only the chlorohydrin of oleic acid was detected.
      Administration of 250-MUM lipid chlorohydrins, which is the concentration found
      in ascitic fluid, induces the expression of TNFalpha and interleukin-1beta in
      peritoneal macrophages and increases the systemic inflammatory response in
      pancreatitis. Finally, increased concentrations of oleic acid chlorohydrin have
      been found in plasma of human patients with pancreatitis. CONCLUSIONS: During
      acute pancreatitis, adipose tissue release FA-Cl, which exacerbate the systemic
      inflammatory response.

PMID- 22964728
TI  - Modulation of murine Alzheimer pathogenesis and behavior by surgery.
AB  - OBJECTIVE: Previous research suggests that a link between anesthetic exposure and
      Alzheimer disease exists. Because anesthetics are rarely given alone, we ask
      whether addition of surgery further modulates Alzheimer disease. BACKGROUND:
      Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces
      cognitive decline in both older wild-type (WT) mice and rats, and the addition of
      surgery produces transient decline in young, adult WT mice. Because
      neuroinflammation has been implicated and occurs early in Alzheimer disease, we
      hypothesized that the neuroinflammatory stress associated with surgery would
      accelerate the progression of Alzheimer disease. METHODS: Cecal ligation and
      excision were performed on presymptomatic 5- to 11-month-old triple-transgenic
      Alzheimer disease (3*TgAD) and C57BL/6 WT mice under desflurane anesthesia.
      Surgery animals were compared with aged-matched 3*TgAD and WT mice exposed to air
      or desflurane alone. Cognitive function was assessed via Morris water maze at 2
      and 13 weeks postoperatively. Amyloid and tau pathology and inflammation and
      synaptic markers were quantified with immunohistochemistry, Luminex assay, enzyme
      linked immunosorbent assay, or Western blot assays. RESULTS: A significant
      cognitive impairment in 3*TgAD mice that underwent surgery compared with air or
      desflurane controls persisted to at least 14 weeks after surgery. Microglial
      activation, amyloidopathy, and tauopathy were enhanced by surgery as compared
      with desflurane alone. No differences between surgery, anesthetic, or air
      controls were detected in WT mice CONCLUSIONS: Surgery causes a durable increment
      in Alzheimer pathogenesis, primarily through a transient activation of
      neuroinflammation.

PMID- 22964730
TI  - Irrigation versus suction alone during laparoscopic appendectomy for perforated
      appendicitis: a prospective randomized trial.
AB  - BACKGROUND: The efficacy of irrigating the peritoneal cavity during appendectomy
      for perforated appendicitis has been debated extensively. To date, prospective
      comparative data are lacking. Therefore, we conducted a prospective, randomized
      trial comparing peritoneal irrigation to suction alone during laparoscopic
      appendectomy in children. METHODS: Children younger than 18 years with perforated
      appendicitis were randomized to peritoneal irrigation with a minimum of 500 mL
      normal saline, or suction only during laparoscopic appendectomy. Perforation was
      defined as a hole in the appendix or fecalith in the abdomen. The primary outcome
      variable was postoperative abscess. Using a power of 0.8 and alpha of 0.05, a
      sample size of 220 patients was calculated. A battery-powered laparoscopic
      suction/irrigator was used in all cases. Pre- and postoperative management was
      controlled. Data were analyzed on an intention-to-treat basis. RESULTS: A total
      of 220 patients were enrolled between December 2008 and July 2011. There were no
      differences in patient characteristics at presentation. There was no difference
      in abscess rate, which was 19.1% with suction only and 18.3% with irrigation (P =
      1.0). Duration of hospitalization was 5.5 +/- 3.0 with suction only and 5.4 +/-
      2.7 days with group (P = 0.93). Mean hospital charges was $48.1K in both groups
      (P = 0.97). Mean operative time was 38.7 +/- 14.9 minutes with suction only and
      42.8 +/- 16.7 minutes with irrigation (P = 0.056). Irrigation was felt to be
      necessary in one case (0.9%) randomized to suction only. In the patients who
      developed an abscess, there was no difference in duration of hospitalization,
      days of intravenous antibiotics, duration of home health care, or abscess-related
      charges. CONCLUSIONS: There is no advantage to irrigation of the peritoneal
      cavity over suction alone during laparoscopic appendectomy for perforated
      appendicitis. The study was registered with clinicaltrials.gov at the inception
      of enrollment (NCT00981136).

PMID- 22964729
TI  - A novel autologous cell-based therapy to promote diabetic wound healing.
AB  - OBJECTIVES: We have previously shown that stromal cell-derived factor-1alpha (SDF
      1alpha) is downregulated within diabetic cutaneous wounds, and that direct
      application of recombinant SDF-1alpha increases wound closure rates,
      neovascularization, and endothelial progenitor cell (EPC) recruitment. However,
      increased wound levels of exogenous SDF-1alpha results in elevated systemic
      levels of this proangiogenic chemokine that raises concerns for tumorigenesis and
      inflammation. We now seek to test the efficacy of a novel, safer cell-based
      therapy (CBT) employing ex vivo primed bone marrow-derived stem cells (BMDSC)
      with SDF-1alpha. We also elucidate the mechanism of action of this new approach
      for accelerating diabetic wound healing. METHODS: Unfractionated BMDSC from
      diabetic Lepr mice were incubated for 20 hours with SDF-1alpha (100 ng/mL) or
      bovine serum albumin (control). Pretreated BMDSC (1 * 10) were injected
      subcutaneously into full-thickness skin wounds in Lepr mice (n = 8 per group).
      Wound closure rates, capillary density, and the recruitment of EPC were assessed
      with serial photography, DiI perfusion, confocal microscopy, and
      immunohistochemistry. The expression of molecular targets, which may mediate
      prohealing/proangiogenic effects of SDF-1alpha-primed BMDSC was evaluated by
      polymerase chain reaction array and immunoblotting assay. The biological function
      of a potential mediator was tested in a mouse wound-healing model. Serum SDF
      1alpha levels were measured with enzyme-linked immunosorbent assay (ELISA).
      RESULTS: SDF-1alpha-primed BMDSC significantly promote wound healing (P <
      0.0001), neovascularization (P = 0.0028), and EPC recruitment (P = 0.0059).
      Gene/protein expression studies demonstrate upregulation of Ephrin Receptor B4
      and plasminogen as downstream targets potentially mediating the prohealing and
      proangiogenic responses. Ex vivo BMDSC activation and the subsequent inoculation
      of cells into wounds does not increase systemic SDF-1alpha levels. CONCLUSIONS:
      We report a novel CBT that is highly effective in promoting healing and
      neovascularization in a murine model of type 2 diabetes. Furthermore, we identify
      new molecular targets that may be important for advancing the field of wound
      healing.

PMID- 22964731
TI  - Progress in the diagnosis of appendicitis: a report from Washington State's
      Surgical Care and Outcomes Assessment Program.
AB  - BACKGROUND AND OBJECTIVES: Studies suggest that computed tomography and
      ultrasonography can effectively diagnose and rule out appendicitis, safely
      reducing negative appendectomies (NAs); however, some within the surgical
      community remain reluctant to add imaging to clinical evaluation of patients with
      suspected appendicitis. The Surgical Care and Outcomes Assessment Program (SCOAP)
      is a physician-led quality initiative that monitors performance by benchmarking
      processes of care and outcomes. Since 2006, accurate diagnosis of appendicitis
      has been a priority for SCOAP. The objective of this study was to evaluate the
      association between imaging and NA in the general community. METHODS: Data were
      collected prospectively for consecutive appendectomy patients (age > 15 years) at
      nearly 60 hospitals. SCOAP data are obtained directly from clinical records,
      including radiological, operative, and pathological reports. Multivariate
      logistic regression models were used to examine the association between imaging
      and NA. Tests for trends over time were also conducted. RESULTS: Among 19,327
      patients (47.9% female) who underwent appendectomy, 5.4% had NA. Among patients
      who were imaged, frequency of NA was 4.5%, whereas among those who were not
      imaged, it was 15.4% (P < 0.001). This association was consistent for men (3% vs
      10%, P < 0.001) and for women of reproductive age (6.9% vs 24.7%, P < 0.001). In
      a multivariate model adjusted for age, sex, and white blood cell count, odds of
      NA for patients not imaged were 3.7 times the odds for those who received imaging
      (95% CI: 3.0-4.4). Among SCOAP hospitals, use of imaging increased and NA
      decreased significantly over time; frequency of perforation was unchanged.
      CONCLUSIONS: Patients who were not imaged during workup for suspected
      appendicitis had more than 3 times the odds of NA as those who were imaged.
      Routine imaging in the evaluation of patients suspected to have appendicitis can
      safely reduce unnecessary operations. Programs such as SCOAP improve care through
      peer-led, benchmarked practice change.

PMID- 22964732
TI  - Liver transplantation for nonalcoholic steatohepatitis: the new epidemic.
AB  - OBJECTIVE: To analyze incidence, outcomes, and utilization of health care
      resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH).
      SUMMARY OF BACKGROUND DATA: With the epidemic of obesity and metabolic syndrome
      in nearly 33% of the US population, NASH is projected to become the leading
      indication for LT in the next several years. Data on predictors of outcome and
      utilization of health care resources after LT in NASH is limited. METHODS: We
      conducted an analysis from our prospective database of 144 adult NASH patients
      who underwent LT between December 1993 and August 2011. Outcomes and resource
      utilization were compared with other common indications for LT. Independent
      predictors of graft and patient survival were identified. RESULTS: The average
      Model for End-Stage Liver Disease score was 33. The frequency of NASH as the
      primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the
      second most common indication for LT at our center behind hepatitis C. NASH
      patients had significantly longer operative times (402 vs 322 minutes; P <
      0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001),
      and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5
      year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable
      with other diagnoses. Age greater than 55 years, pretransplant intubation,
      dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor
      age greater than 55 years, and cold ischemia time greater than 550 minutes were
      significant independent predictors of survival for all patients, whereas body
      mass index greater than 35 was a predictor in NASH patients only. CONCLUSIONS: We
      report the largest single institution experience of LT for NASH. Over a 10-year
      period, the frequency of LT for NASH has increased 5-fold. Although outcomes are
      comparable with LT for other indications, health care resources are stressed
      significantly by this new and increasing group of transplant candidates.

PMID- 22964733
TI  - Naturally occurring immunoglobulin M (nIgM) autoantibodies prevent autoimmune
      diabetes and mitigate inflammation after transplantation.
AB  - OBJECTIVE: To investigate whether polyclonal serum naturally occurring
      immunoglobulin M (nIgM) therapy prevents the onset and progression of autoimmune
      diabetes and promotes islet allograft survival. BACKGROUND: nIgM deficiency is
      associated with an increased tendency toward autoimmune disease development.
      Elevated levels of nIgM anti-leukocyte autoantibodies are associated with fewer
      graft rejections. METHODS: Four- to five-week-old female nonobese diabetic (NOD)
      littermates received intraperitoneal nIgM or phosphate-buffered saline/bovine
      serum albumin/immunoglobulin G (100 MUg followed by 50-75 MUg biweekly) until 18
      weeks of age. C57BL/6 recipients of 300 BALB/c or 50 C57BL/6 islet grafts
      received saline or nIgM. RESULTS: Eighty percent control mice (n = 30) receiving
      saline became diabetic by 18 to 20 weeks of age. In contrast, none of 33 of nIgM
      treated mice became diabetic (P < 0.0001). Discontinuing therapy resulted in
      hyperglycemia in only 9 of 33 mice at 22 weeks postdiscontinuation, indicating
      development of beta-cell unresponsiveness. nIgM therapy initiated at 11 weeks of
      age resulted in hyperglycemia in only 20% of treated animals (n = 20) compared
      with 80% of controls (P < 0.0001). Treatment of mildly diabetic mice with nIgM
      (75 MUg 3* per week) restored normoglycemia (n = 5), whereas severely diabetic
      mice required minimal dose islet transplant with nIgM to restore normoglycemia (n
      = 4). The mean survival time of BALB/c islet allografts transplanted in
      streptozotocin-induced diabetic C57BL/6 mice was 41.2 +/- 3.3 days for nIgM
      treated recipients (n = 4, fifth recipient remains normoglycemic) versus 10.2 +/-
      2.6 days for controls (n = 5) (P < 0.001). Also, after syngeneic transplantation,
      time taken to return to normoglycemia was 15.4 +/- 3.6 days for nIgM-treated
      recipients (n = 5) and more than 35 days for controls (n = 4). CONCLUSIONS: nIgM
      therapy demonstrates potential in preventing the onset and progression of
      autoimmune diabetes and in promoting islet graft survival.

PMID- 22964734
TI  - Institutional factors beyond procedural volume significantly impact center
      variability in outcomes after orthotopic heart transplantation.
AB  - OBJECTIVE: To evaluate the contribution of institutional volume and other
      unmeasured institutional factors beyond volume to the between-center variability
      in outcomes after orthotopic heart transplantation (OHT). BACKGROUND: It is
      unclear if institutional factors beyond volume have a significant impact on OHT
      outcomes. METHODS: The United Network for Organ Sharing registry was used to
      identify OHTs performed between 2000 and 2010. Separate mixed-effect logistic
      regression models were constructed, with the primary endpoint being post-OHT
      mortality. Model A included only individual centers, model B added validated
      recipient and donor risk indices as well as the year of transplantation, and
      model C added institutional volume as a continuous variable to model B. The
      reduction in between-center variability in mortality between models B and C was
      used to define the contribution of institutional volume. Kaplan-Meier survival
      curves were also compared after stratifying patients into equal-size tertiles
      based on center volume. RESULTS: A total of 119 centers performed OHT in 19,156
      patients. After adjusting for transplantation year and differences in recipient
      and donor risk, decreasing center volume was associated with an increased risk of
      1-year mortality (P < 0.001). However, procedural volume only accounted for 16.7%
      of the variability in mortality between centers, and significant between-center
      variability persisted after adjusting for institutional volume (P<0.001). In
      Kaplan-Meier analysis, there was significant variability in 1-year survival
      between centers within each volume category: low-volume (66.7%-96.6%),
      intermediate-volume (80.7%-97.3%), and high-volume (83.8%-93.9%). These trends
      were also observed with 5-year mortality. CONCLUSIONS: This large-cohort analysis
      demonstrates that although institutional volume is a significant predictor of
      post-OHT outcomes, there are other unmeasured institutional factors that
      contribute substantially to the between-center variability in outcomes.
      Institutional volume should therefore not be the sole indicator of "center
      quality" in OHT.

PMID- 22964735
TI  - Hospital procedure volume should not be used as a measure of surgical quality.
AB  - INTRODUCTION: The Agency for Healthcare Research and Quality and the Leapfrog
      Group use hospital procedure volume as a quality measure for pancreatic resection
      (PR), abdominal aortic aneurysm (AAA) repair, esophageal resection (ER), and
      coronary artery bypass grafting (CABG). However, controversy exists regarding the
      strength and validity of the evidence for the volume-outcome association. The
      purpose of this study was to reevaluate the volume-outcome relationship for these
      procedures. METHODS: Discharge data for 261,412 patients were extracted from the
      2008 Nationwide Inpatient Sample. The relationship between hospital procedure
      volume and mortality was rigorously assessed using hierarchical general linear
      modeling with restricted cubic splines, adjusted for patient demographics,
      comorbid disease, and elective procedure status. RESULTS: Unadjusted mortality
      rates were PR (4.7%), AAA (12.7%), ER (5.8%), and CABG (2.2%), and the majority
      of operations were elective. Hospital procedure volume was not a statistically
      significant predictor of in-hospital mortality for any of the 4 procedures.
      Strong predictors of mortality included age, elective procedure status, renal
      failure, and malnutrition (P < 0.001). Each of the models demonstrated excellent
      performance in estimating the probability of death. CONCLUSIONS: Hospital
      procedure volume is not a significant predictor of mortality for the performance
      of pancreatectomy, AAA repair, esophagectomy, or CABG. Procedure volume by itself
      should not be used as a proxy measure for surgical quality. Patient mortality
      risk is primarily attributable to patient-level characteristics such as age and
      comorbidity.

PMID- 22964736
TI  - Causes and implications of readmission after abdominal aortic aneurysm repair.
AB  - OBJECTIVE: To determine the frequency, causes, predictors, and consequences of 30
      day readmission after abdominal aortic aneurysm (AAA) repair. BACKGROUND DATA:
      Centers for Medicare & Medicaid Services (CMS) will soon reduce total Medicare
      reimbursements for hospitals with higher-than-predicted 30-day readmission rates
      after vascular surgical procedures, including AAA repair. However, causes and
      factors leading to readmission in this population have never before been
      systematically analyzed. METHODS: We analyzed elective AAA repairs over a 2-year
      period from the CMS Chronic Conditions Warehouse, a 5% national sample of
      Medicare beneficiaries. RESULTS: A total of 2481 patients underwent AAA repair-
      1502 endovascular aneurysm repair (EVAR) and 979 open aneurysm repair. Thirty-day
      readmission rates were equivalent for EVAR (13.3%) and open repair (12.8%).
      Although wound complication was the most common reason for readmission after both
      procedures, the relative frequency of other causes differed-eg, bowel obstruction
      was common after open repair, and graft complication after EVAR. In multivariate
      analyses, preoperative comorbidities had a modest effect on readmission; however,
      postoperative factors, including serious complications leading to prolonged
      length of stay and discharge destination other than home, had a profound
      influence on the probability of readmission. The 1-year mortality in readmitted
      patients was 23.4% versus 4.5% in those not readmitted (P < 0.001). CONCLUSIONS:
      Early readmission is common after AAA repair. Adjusting for comorbidities,
      postoperative events predict readmission, suggesting that proactively preventing,
      detecting, and managing postoperative complications may provide an approach to
      decreasing readmissions, with the potential to reduce cost and possibly enhance
      long-term survival.

PMID- 22964738
TI  - Safety of colloids:  a knowledge issue?

PMID- 22964737
TI  - Changes in abdominal aortic aneurysm rupture and short-term mortality, 1995-2008:
      a retrospective observational study.
AB  - OBJECTIVE: To examine the modern epidemiology of abdominal aortic aneurysm (AAA)
      rupture and short-term AAA-related mortality after the introduction of
      endovascular aneurysm repair (EVAR). BACKGROUND: Previous epidemiologic studies
      have demonstrated stable rates of AAA repair, repair mortality, and AAA rupture.
      Recently, EVAR has been introduced as a less invasive treatment method, and its
      use has expanded to more than 75% of elective AAA repairs. METHODS: We identified
      Medicare beneficiaries undergoing AAA repair and those hospitalized with a
      ruptured AAA during the period 1995 to 2008 and calculated standardized annual
      rates of AAA-related deaths due to either elective repair or rupture. RESULTS: A
      total of 338,278 patients underwent intact AAA repair during the study period.
      There were 69,653 patients with AAA rupture, of whom 47,524 underwent repair.
      Intact repair rates increased substantially in those older than 80 years (57.7
      92.3 per 100,000, P < 0.001) but decreased in those 65 to 74 years old (81.8
      68.9, P < 0.001). A decline in ruptures with and without repair was seen in all
      age groups. By 2008, 77% of all intact repairs and 31% of all rupture repairs
      were performed with EVAR (P < 0.001). Operative mortality declined during the
      study period for both intact (4.9%-2.4%, P < 0.001) and ruptured (44.1%-36.3%, P
      < 0.001) AAA repair. Short-term AAA-related deaths decreased by more than half
      (26.1-12.1 per 100,000, P < 0.001), with the greatest decline occurring in those
      older than 80 years (53.7-27.3, P < 0.001). CONCLUSIONS: A recent decline in AAA
      rupture and short-term AAA-related mortality is demonstrated and likely related
      in part to the introduction and expansion of EVAR. This is due to decreased
      deaths from ruptures (with and without repair) and decreased mortality with
      intact repairs, particularly in patients older than 80 years.

PMID- 22964739
TI  - Overuse of preoperative cardiac stress testing in medicare patients undergoing
      elective noncardiac surgery.
AB  - OBJECTIVE: To determine the frequency and predictors of cardiac stress testing
      before elective noncardiac surgery in Medicare patients with no indications for
      cardiovascular evaluation. BACKGROUND: The American College of
      Cardiology/American Heart Association guidelines indicate that patients without
      class I (American Heart Association high risk) or class II cardiac conditions
      (clinical risk factors) should not undergo cardiac stress testing before elective
      noncardiac, nonvascular surgery. METHODS: We used 5% Medicare inpatient claims
      data (1996-2008) to identify patients aged >= 66 years who underwent elective
      general surgical, urological, or orthopedic procedures (N = 211,202). We examined
      the use of preoperative stress testing in the subset of patients with no
      diagnoses consistent with cardiac disease (N = 74,785). Bivariate and
      multivariate analyses were used to identify predictors of preoperative cardiac
      stress testing. RESULTS: Of the patients with no cardiac indications for
      preoperative stress testing, 3.75% (N = 2803) received stress testing in the 2
      months before surgery. The rate of preoperative stress testing increased from
      1.72% in 1996 to 6.44% in 2007 (P < 0.0001). A multivariate analysis adjusting
      for patient and hospital characteristics showed a significant increase in
      preoperative stress testing over time. Female sex [odds ratio (OR) 1.11; 95% CI:
      1.02-1.21], presence of other comorbidities [OR 1.22; 95% confidence interval
      (CI): 1.09-1.35], high-risk procedure (OR 2.42; 95% CI: 2.04-2.89), and larger
      hospital size (OR 1.17; 95% CI: 1.03-1.32) were positive predictors of stress
      testing. Patients living in regions with greater Medicare expenditures (OR 1.24;
      95% CI: 1.05-1.45) were also more likely to receive stress tests. CONCLUSIONS: In
      a 5% sample of Medicare claims data, 2803 patients underwent preoperative stress
      testing without any indications. When these results were applied to the entire
      Medicare population, we estimated that there are over 56,000 patients who
      underwent unnecessary preoperative stress testing. The rate of testing in
      patients without cardiac indications has increased significantly over time.

PMID- 22964740
TI  - Issues in general surgery residency training--2012.

PMID- 22964741
TI  - A prospective study of expectant observation as primary therapy for neuroblastoma
      in young infants: a Children's Oncology Group study.
AB  - OBJECTIVE: To demonstrate that expectant observation of young infants with small
      adrenal masses would result in excellent event-free and overall survival.
      BACKGROUND: Neuroblastoma is the most common malignant tumor in infants, and in
      young infants, 90% of neuroblastomas are located in the adrenal gland. Although
      surgical resection is standard therapy, multiple observations suggest that
      expectant observation could be a safe alternative for infants younger than 6
      months who have small adrenal masses. METHODS: A prospective study of infants
      younger than 6 months with small adrenal masses and no evidence of spreading
      beyond the primary tumor was performed at participating Children's Oncology Group
      institutions. Parents could choose observation or immediate surgical resection.
      Serial abdominal sonograms and urinary vanillylmandelic acid and homovanillic
      acid measurements were performed during a 90-week interval. Infants experiencing
      a 50% increase in the volume of the mass, urine catecholamine values, or an
      increase in the homovanillic acid to vanillylmandelic acid ratio greater than 2,
      were referred for surgical resection. RESULTS: Eighty-seven eligible patients
      were enrolled: 83 elected observation and 4 chose immediate surgery. Sixteen
      observational patients ultimately had surgery; 8 had International Neuroblastoma
      Staging System stage 1 neuroblastoma, 2 had higher staged neuroblastoma (2B and
      4S), 2 had low-grade adrenocortical neoplasm, 2 had adrenal hemorrhage, and 2 had
      extralobar pulmonary sequestration. The 2 patients with adrenocortical tumors
      were resected because of a more than 50% increase in tumor volume. The 3-year
      event-free survival for a neuroblastoma event was 97.7 +/- 2.2% within the entire
      cohort of patients (n = 87). The 3-year overall survival was 100%, with a median
      follow-up of 3.2 years. Eighty-one percent of patients on the observation arm
      were spared resection. CONCLUSIONS: Expectant observation of infants younger than
      6 months with small adrenal masses led to excellent event-free survival and
      overall survival while avoiding surgical intervention in a large majority of the
      patients.

PMID- 22964744
TI  - Diagnostic pathways for interstitial lung  diseases in primary care.

PMID- 22964742
TI  - A prevalent and three novel mutations in CYP11B1 gene identified in Chinese
      patients with 11-beta hydroxylase deficiency.
AB  - 11beta-Hydroxylase deficiency (11beta-OHD), caused by CYP11B1 mutations, is
      characterized by hyporeninemic, hypokalemic hypertension and hyperandrogenism. We
      identified a prevalent and three novel mutations of CYP11B1 gene in nine patients
      with classic 11beta-OHD. SUBJECTS AND METHODS: Nine patients with 11beta-OHD from
      unrelated families were recruited. The complications of 11beta-OHD occurred in
      three patients who never received glucocorticoid treatment. CYP11B1 gene was
      sequenced and 11beta-hydroxylase enzymatic activities were assessed in vitro. A
      haplotype analysis was performed to determine a common ancestor for those
      subjects who carried the same p.R454C mutation. RESULTS: CYP11B1 gene mutations
      were identified in all patients, with a prevalent (p.R454C) and three novel
      mutations (p.V148G, IVS7-9C>A, c.1359_1360insG). The p.R141X, p.V148G,
      c.1359_1360insG and p.R454C mutations retained 4.9%, 3.9%, 3.7%, 4.5% of residual
      enzymatic activity, respectively. Five of nine patients carried p.R454C mutation,
      which was only reported in Chinese 11OHD patients. Haplotype analysis showed that
      this mutation might be inherited from a common ancestor. CONCLUSION: The
      enzymatic activities for p.R141X, p.V148G, c.1359_1360insG and p.R454C mutants
      were almost completely abolished, which corresponds to classic form of 11beta
      OHD. The observations of a prevalent mutation and three novel mutations might
      have potential clinical utility for genetic counseling and prenatal diagnosis in
      Chinese 11beta-OHD patients.

PMID- 22964745
TI  - A 54 year-old man with a chronic cough--A primary care perspective from Canada.

PMID- 22964746
TI  - A 54 year-old man with a chronic cough--A primary care perspective from
      Argentina.

PMID- 22964747
TI  - A 54 year-old man with a chronic cough--Following referral: a secondary care
      perspective from the UK.

PMID- 22964748
TI  - A 54 year-old man with a chronic cough--Chronic cough: don't forget drug-induced
      causes.

PMID- 22964749
TI  - High incidence of triple-negative tumors in sub-saharan Africa: a prospective
      study of breast cancer characteristics and risk factors in Malian women seen in a
      Bamako university hospital.
AB  - OBJECTIVE: Few studies have been conducted on breast cancer in Sub-Saharan Africa
      and their results have been suspected to be impaired by artefacts. This
      prospective study was designed to determine tumor and patient characteristics in
      Mali with control of each methodological step. These data are necessary to define
      breast cancer treatment guidelines in this country. METHODS: Clinical and tumor
      characteristics and known risk factors were obtained in a consecutive series of
      114 patients. Each technical step for the determination of tumor characteristics
      [histology, TNM, grade, estrogen (ER) and progesterone receptors (PR), HER2, and
      Ki67] was controlled. RESULTS: Patients had a mean age of 46 years. Most tumors
      were invasive ductal carcinomas (94%), T3-T4 (90%) with positive nodes (91%),
      grade III (78%), and ER (61%) and PR (72%) negative. HER2 was overexpressed in
      18% of cases. The triple-negative subgroup represented 46%, displaying a
      particularly aggressive pattern (90% grade III; 88% Ki67 >20%). CONCLUSION: This
      study demonstrates the high incidence of aggressive triple-negative tumors in
      Mali. Apart from a higher prevalence of premenopausal women, no significant
      difference in risk factors was observed between triple-negative tumors and other
      tumors. The hormonal therapy systematically prescribed therefore needs to be
      revised in light of this study.

PMID- 22964750
TI  - Terminal-restriction fragment length polymorphism (T-RFLP) analysis for changes
      in the gut microbiota profiles of indomethacin- and rebamipide-treated mice.
AB  - BACKGROUND/AIMS: We investigated the effects of indomethacin and rebamipide on
      the gut microbiota profiles using terminal restriction fragment polymorphism (T
      RFLP) analysis. MATERIALS AND METHODS: Female C57BL/6J mice were given
      indomethacin (10 mg/kg, s.c.) once a day and 2.5 mg rebamipide orally 3 times a
      day. After 7 days, they were sacrificed, and luminal contents were obtained from
      the ileum and cecum. The gut microbiota communities were analyzed by T-RFLP
      analysis with BslI digestion. RESULTS: T-RFLP analyses showed that rebamipide and
      indomethacin had no significant effects on the gut microbiota profiles in the
      ileum and cecum. In contrast, the combination of rebamipide + indomethacin
      induced a significant change in the gut microbiota. The changes in the microbiota
      composition induced by the combination of rebamipide + indomethacin were
      characterized by the increase in the orders Bifidobacteriales and
      Lactobacillales, the genera Bacteroides and Prevotella and the family
      Clostridiaceae. The diversity of the gut microbiota community generated by the
      combination of rebamipide + indomethacin was significantly higher than those
      induced by either rebamipide or indomethacin alone. CONCLUSION: The combination
      of rebamipide + indomethacin induces remarkable changes in the gut microbiota
      composition and diversity. The clinical activity of rebamipide on nonsteroidal
      anti-inflammatory drug-induced intestinal injury may be exerted through a
      modulation of the gut microbiota.

PMID- 22964751
TI  - Urinary tract infection analysis in a spinal cord injured population undergoing
      rehabilitation--how to treat?
AB  - STUDY DESIGN: Cross sectional study, including 38 outpatients. Standardized
      questionnaire was used and urine cultures were performed. OBJECTIVES: To study
      spinal cord-injured (SCI) patients bladder management, clinical aspects that
      symptomatic urinary tract infection (SUTI) may present and asymptomatic
      bacteriuria (AB) incidence with its antimicrobial susceptibility profile.
      SETTING: Spinal cord injury outpatient rehabilitation clinic. RESULTS: Clean
      intermittent catheterization is used by 71% of the patients. SUTI may have
      atypical clinical presentation (shivers, spasticity increase, headaches). In
      total, 65.7% (N=25) of the patients presented AB. Among these, the microorganisms
      isolated were resistant mainly to Ampicillin, Sulfamethoxazole-Trimethoprim and
      Norfloxacin, whose resistance rates were, respectively 73.3%, 60% and 33.3%.
      CONCLUSION: Special attention should be given to possible atypical symptoms for
      SUTI. Although a small amount of urine samples was analyzed, resistance rates
      against Ampicillin, Sulfamethoxazole-Trimethoprim, Ciprofloxacin and
      Nitrofurantoin appear to be higher among SCI patients compared to the general
      population, thus demonstrating the need for continuous monitoring of
      microorganisms susceptibility, in order to avoid therapeutic failure when dealing
      with this specific population.

PMID- 22964752
TI  - Morbidity of urinary tract infection after urodynamic examination of hospitalized
      SCI patients: the impact of bladder management.
AB  - STUDY DESIGN: Non-interventional, descriptive-observational cohorts study.
      OBJECTIVES: To assess the incidence of urinary tract infection (UTI) after
      urodynamic examination in patients with spinal cord injury (SCI) according to
      bladder management. SETTING: Level 1 trauma center. METHODS: Between January and
      December 2010 a total of 133 consecutive, hospitalized SCI patients were included
      and classified according to their bladder management. Urine specimen was obtained
      at the beginning of the urodynamic studies (UDS) and 3-5 days thereafter.
      'Significant bacteriuria' (SBU) is defined by a CBU per ml level >=10(5) in a
      urine culture. UTI thus is defined as a combination of a SBU and >=100 leukocytes
      per MUl in urine analysis. RESULTS: The overall incidence of UTI post UDS was
      15.79%. In patients with sterile urine prior to urodynamics UTI was ascertained
      in 8.6% (de-novo-UTI). In contrast, 32.5% of the patients with SBU prior to UDS
      showed UTI 3 days later. There were only minor differences in the incidence of de
      novo-UTIs in SCI patients who emptied their bladder by intermittent self
      catheterization or intermittent catheterization by attendant (8.82% and 6.67%,
      respectively). In SCI patients with reflex voiding however, the frequency of de
      novo-UTIs was twice as high (14.28%). CONCLUSION: The recommendation of
      antibiotic prophylaxis for all SCI patients undergoing urodynamic examination is
      not commonly accepted and according to our data not justified. However, the
      analysis of subgroups revealed that SCI patients with unsuspected SBU prior to
      UDS and patients with reflex voiding are possibly at higher risk to acquire post
      UDS infection.

PMID- 22964753
TI  - Positive and negative affect in individuals with spinal cord injuries.
AB  - STUDY DESIGN: Participants with spinal cord injuries (SCIs) and healthy controls
      completed standardized questionnaires assessing depression level, positive and
      negative affect, and personality traits. OBJECTIVES: To identify the specific
      characteristics of emotional experiences affected by spinal cord injury. SETTING:
      A Canadian rehabilitation center. Individuals with SCIs were recruited from a
      list of patients who had volunteered to participate in studies being conducted by
      the SCI clinic. Healthy controls were recruited from the community, but tested in
      the SCI clinic. METHODS: Thirty-six individuals with complete (ASIA A) SCIs and
      36 age-, gender- and education-matched controls participated in this study. SCI
      participants were classified as cervical (C1-C7), upper thoracic (T1-T5) or lower
      thoracic/upper lumbar (T6-L2). All participants completed the Beck Depression
      Inventory, the Positive and Negative Affect Schedules, the NEO Neuroticism
      Questionnaire, and the harm avoidance scale of the Tridimensional Personality
      Questionnaire. Data were analyzed using independent-samples t-tests (when
      contrasting SCI and controls) and analysis of variance (when comparing across SCI
      groups). RESULTS: Participants with SCIs experienced significantly less positive
      affect than controls. The two groups did not differ in their experience of
      negative affect. Participants with SCIs also reported greater levels of
      depression. Depression scores improved with an increasing number of years post
      injury. CONCLUSION: Individuals with SCIs are characterized by specific emotional
      dysfunction related to the experience of positive emotions, rather than a
      tendency to ruminate on negative emotions. The results suggest that these
      individuals would benefit from rehabilitation programs that include training in
      positive psychology.

PMID- 22964754
TI  - Childhood abuse, sexual function and cortisol levels in eating disorders.

PMID- 22964755
TI  - Freely chosen cadence during a covert manipulation of ambient temperature.
AB  - The present study investigated relationships between changes in power output (PO)
      to torque (TOR) or freely chosen cadence (FCC) during thermal loading. Twenty
      participants cycled at a constant rating of perceived exertion while ambient
      temperature (Ta) was covertly manipulated at 20-min intervals of 20  degrees C,
      35  degrees C, and 20  degrees C. The magnitude responses of PO, FCC and TOR were
      analyzed using repeated-measures ANOVA, while the temporal correlations were
      analyzed using Auto-Regressive Integrated Moving Averages (ARIMA). Increases in
      Ta caused significant thermal strain (p < .01), and subsequently, a decrease in
      PO and TOR magnitude (p < .01), whereas FCC remained unchanged (p = .51). ARIMA
      indicates that changes in PO were highly correlated to TOR (stationary r2 = .954,
      p = .04), while FCC was moderately correlated (stationary r2 = .717, p = .01) to
      PO. In conclusion, changes in PO are caused by a modulation in TOR, whereas FCC
      remains unchanged and therefore, unaffected by thermal stressors.

PMID- 22964756
TI  - Diastereoselective ruthenium porphyrin-catalyzed tandem nitrone formation/1,3
      dipolar cycloaddition for isoxazolidines. Synthesis, in silico docking study and
      in vitro biological activities.
AB  - Ruthenium porphyrin catalyzes tandem nitrone formation/1,3-dipolar cycloaddition
      of diazo compounds, nitrosoarenes and alkenes to form isoxazolidines in good to
      high yields and with excellent regio-, chemo- and diastereo-selectivities. A
      broad substrate scope of alkenes is applicable to this protocol and various
      functional groups are compatible with the reaction conditions. In silico analysis
      and in vitro biological experiments revealed that some of the new isoxazolidines
      synthesized in this work could act as leukotriene A4 hydrolase inhibitors.

PMID- 22964757
TI  - Hairless promotes PPARgamma expression and is required for white adipogenesis.
AB  - Adipose tissue is the largest compartment in the mammalian body for storing
      energy as fat, providing an important reservoir of fuel for maintaining whole
      body energy homeostasis. Herein, we identify the transcriptional cofactor
      hairless (HR) to be required for white adipogenesis. Moreover, forced expression
      of HR in non-adipogenic precursor cells induces adipogenic gene expression and
      enhances adipocyte formation under permissive conditions. HR exerts its
      proadipogenic effects by regulating the expression of PPARgamma, one of the
      central adipogenic transcription factors. In conclusion, our data provide a new
      mechanism required for white adipogenesis.

PMID- 22964759
TI  - Mitofusins 'bridge' the gap between oxidative stress and mitochondrial
      hyperfusion.

PMID- 22964760
TI  - Evaluation of robustness of maximum likelihood cone-beam CT reconstruction with
      total variation regularization.
AB  - The objective of this paper is to evaluate an iterative maximum likelihood (ML)
      cone-beam computed tomography (CBCT) reconstruction with total variation (TV)
      regularization with respect to the robustness of the algorithm due to data
      inconsistencies. Three different and (for clinical application) typical classes
      of errors are considered for simulated phantom and measured projection data:
      quantum noise, defect detector pixels and projection matrix errors. To quantify
      those errors we apply error measures like mean square error, signal-to-noise
      ratio, contrast-to-noise ratio and streak indicator. These measures are derived
      from linear signal theory and generalized and applied for nonlinear signal
      reconstruction. For quality check, we focus on resolution and CT-number linearity
      based on a Catphan phantom. All comparisons are made versus the clinical
      standard, the filtered backprojection algorithm (FBP). In our results, we confirm
      and substantially extend previous results on iterative reconstruction such as
      massive undersampling of the number of projections. Errors of projection matrix
      parameters of up to 1 degrees  projection angle deviations are still in the
      tolerance level. Single defect pixels exhibit ring artifacts for each method.
      However using defect pixel compensation, allows up to 40% of defect pixels for
      passing the standard clinical quality check. Further, the iterative algorithm is
      extraordinarily robust in the low photon regime (down to 0.05 mAs) when compared
      to FPB, allowing for extremely low-dose image acquisitions, a substantial issue
      when considering daily CBCT imaging for position correction in radiotherapy. We
      conclude that the ML method studied herein is robust under clinical quality
      assurance conditions. Consequently, low-dose regime imaging, especially for daily
      patient localization in radiation therapy is possible without change of the
      current hardware of the imaging system.

PMID- 22964761
TI  - Plasticity of verbal fluency in older adults: a 90-minute telephone-based
      intervention.
AB  - BACKGROUND: There is evidence for specific age-related deficits in tasks of
      verbal fluency. OBJECTIVE: The aim of the present study was to evaluate training
      and transfer effects after 3 weeks of telephone-based verbal fluency training in
      old age. METHODS: Participants were assigned to one of three training groups, an
      active control group, or a no-contact control group. Training consisted of 15
      sessions of 6 min each over a period of 3 weeks. For the training tasks,
      different versions of the verbal fluency task were used, each targeting a
      specific underlying cognitive process (i.e., processing speed, shifting, or
      inhibition). To measure transfer effects, a neuropsychological test battery
      including digit symbol substitution, trail making, go/no-go, digit span, n-back,
      and a verbal learning and memory test was administered before and after training.
      RESULTS: Our findings revealed training gains for initial letter fluency training
      and phonemic switching training, but not for excluded letter fluency training.
      Moreover, after initial letter fluency training and phonemic switching training,
      transfer to other verbal fluency tasks was found. In addition, phonemic switching
      training led to improvement in an untrained short-term memory task. CONCLUSION:
      The findings demonstrate that a telephone-based cognitive intervention of overall
      90 min significantly improved cognitive performance in healthy older adults above
      and beyond the improvements in the active control group. The findings provide the
      basis for cognitive interventions that could easily be integrated into everyday
      lifestyles and are still targeting specific cognitive functions.

PMID- 22964758
TI  - Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for
      cancer therapy.
AB  - The Rho-associated (ROCK) serine/threonine kinases have emerged as central
      regulators of the actomyosin cytoskeleton, their main purpose being to promote
      contractile force generation. Aided by the discovery of effective inhibitors such
      as Y27632, their roles in cancer have been extensively explored with particular
      attention focused on motility, invasion and metastasis. Recent studies have
      revealed a surprisingly diverse range of functions of ROCK. These insights could
      change the way ROCK inhibitors might be used in cancer therapy to include the
      targeting of stromal rather than tumour cells, the concomitant blocking of ROCK
      and proteasome activity in K-Ras-driven lung cancers and the combination of ROCK
      with tyrosine kinase inhibitors for treating haematological malignancies such as
      chronic myeloid leukaemia. Despite initial optimism for therapeutic efficacy of
      ROCK inhibition for cancer treatment, no compounds have progressed into standard
      therapy so far. However, by carefully defining the key cancer types and expanding
      the appreciation of ROCK's role in cancer beyond being a cell-autonomous promoter
      of tumour cell invasion and metastasis, the early promise of ROCK inhibitors for
      cancer therapy might still be realized.

PMID- 22964762
TI  - A case of IgG4-related retroperitoneal fibrosis mimicking renal pelvic cancer.
AB  - IgG4-related sclerosing disease is a novel clinicopathological entity
      characterized by fibrosis, extensive infiltration of IgG4-positive plasma cells,
      and serum IgG4 elevation. This disorder includes a variety of diseases, such as
      autoimmune pancreatitis, retroperitoneal fibrosis, sialadenitis, thyroiditis,
      inflammatory abdominal aneurysm, tubulointerstitial nephritis, and inflammatory
      pseudotumor [World J Gastroenterol 2008;14:3948-3955]. A 71-year-old man visited
      our hospital with the complaint of left flank pain and gross hematuria. Computed
      tomography (CT) revealed left hydronephrosis and a thick retroperitoneal soft
      tissue mass around the ureteropelvic junction, suspicious of renal pelvic cancer.
      Urine cytology using a urine sample from the left renal pelvis was negative. On
      laboratory examination, serum levels of IgG and IgG4 were found to be elevated.
      The patient refused tumor biopsy. Therefore, he was treated with corticosteroid
      therapy on the basis of a clinical diagnosis with IgG4-related retroperitoneal
      fibrosis. Regression of the retroperitoneal mass as well as improvement of left
      hydronephrosis and decrease in serum IgG4 levels were accomplished. These effects
      strongly suggested that the present case was an IgG4-related retroperitoneal
      fibrosis. However, in this instance, since we could not completely rule out
      malignancies by biopsy, careful follow-up was necessary with these points in
      mind.

PMID- 22964763
TI  - Enhanced fluorescence detection using liquid-liquid extraction in a microfluidic
      droplet system.
AB  - Reducing the fluorescence background in microfluidic assays is important in
      obtaining accurate outcomes and enhancing the quality of detections. This study
      demonstrates an integrated process including cell labelling, fluorescence
      background reduction, and biomolecule detection using liquid-liquid extraction in
      a microfluidic droplet system. The cellular lipids in Chlorella vulgaris and
      NIH/3T3 cells were labelled with a hydrophobic dye, Nile red, to investigate the
      performance of the proposed method. The fluorescence background of the lipid
      detection can be reduced by 85% and the removal efficiency increased with the
      volume of continuous phase surrounding a droplet. The removal rate of the
      fluorescence background increased as the surface area to volume ratio of a
      droplet increased. Before Nile red was removed from the droplet, the signal to
      noise ratio was as low as 1.30 and it was difficult to distinguish cells from the
      background. Removing Nile red increased the signal to noise ratio to 22 and 34
      for Chlorella vulgaris and NIH/3T3, respectively, and these were 17 fold and 10
      fold of the values before extraction. The proposed method successfully
      demonstrates the enhancement of fluorescence detection of cellular lipids and has
      great potential in improving other fluorescence-based detections in microfluidic
      systems.

PMID- 22964764
TI  - Protein C polymorphism and susceptibility to PTE in China.
AB  - Pulmonary thromboembolism (PTE) is a common clinical problem that is associated
      with substantial morbidity and mortality. We investigated the role of protein C
      polymorphism in patients with PTE in order to find out the correlation between
      its polymorphism and the susceptibility of the Chinese population to develop PTE.
      We used a case-control study design. Sixty-three consecutive patients with PTE
      were enrolled as the investigated group and 86 healthy people as the control
      group. Two novel polymorphisms, C/T at the position of 2405 and A/G at the
      position of 2418in the protein C gene promoter region were detected through PCR
      restriction fragment length polymorphism analysis. The results suggested that the
      genotype frequencies of the two single-nucleotide polymorphisms (SNPs) when
      combined together were not significantly different between the case and control
      group (P > 0.05). However, the allele frequency of the C2405T SNP was
      significantly different between the case and control group. The frequency of T
      allele in the PTE group was higher when compared to the control, whereas the
      frequency of C allele was lower (P < 0.05). These results suggested that there
      were six different kinds of genotype distribution (TA-TA, TA-CA, TA-CG, CG-CG, CA
      CG, CA-CA) and three different kinds of haplotype (TA, CG, CA). Our result showed
      that the frequency of the TA haplotype was significantly higher in the patients
      suffering from PTE (P < 0.05). These results suggest that the two polymorphisms
      present in the control region of the protein C gene are associated with an
      increased susceptibility to PTE in the Chinese population. The 2405T allele may
      be a possible risk factor for the development of PTE, whereas the C allele may
      probably be a protective factor of PTE Moreover, the TA haplotype may also be
      associated with an increased risk for developing PTE.

PMID- 22964765
TI  - Different cardiac tissue plasminogen activator release patterns by local
      stimulation of the endothelium and sympathetic nerves in pigs.
AB  - Myocardial ischemia induces cardiac tissue plasminogen activator (tPA) release,
      declining by repeated periods of ischemia. However, the mechanisms and cellular
      sources are unknown. Sympathetic nerve stimulation (SS) and bradykinin (BK), an
      endogenous inducer of endothelial tPA release, may play roles, potentially
      involving different sources or mechanisms revealed by different release patterns.
      Therefore, we compared the cardiac tPA release patterns during repeated coronary
      BK infusions and SS, both with an ensuing period of local myocardial
      ischemia/reperfusion (I/R). Nine pigs were subjected to four periods of coronary
      BK infusion (4 min) and another nine animals to four periods of SS (4 min).
      Finally, 10 min of I/R was induced in both groups. The single-peaked BK-induced
      tPA release declined toward baseline by repeated infusions, but tPA release
      reappeared during I/R. In contrast, total tPA release during repeated SS and
      subsequent I/R was more stable, and SS-induced total tPA and norepinephrine (NE)
      releases were strongly correlated. Surprisingly, the instantaneous SS-induced tPA
      release was biphasic with a stable first peak, and a second peak declining toward
      baseline by repeated stimulations. The fluctuations in cardiac release of
      plasminogen activator inhibitor-1 and the endogenous BK inhibitor angiotensin
      converting enzyme, could not explain the diverging tPA release patterns.
      Different tPA release patterns were demonstrated during SS and BK stimulation, as
      well as diverging responses to repeated stimulations and subsequent I/R. This
      study demonstrates strong association between tPA and NE during SS and possibly
      two different sources or mechanisms for SS-induced tPA release.

PMID- 22964766
TI  - Successful use of fondaparinux in a child with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin
      therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for
      initial thrombosis are antiphospholipid syndrome and heterozygous mutation for
      prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was
      effective, but discontinuation of warfarin after 12 months resulted in recurrence
      of thrombosis. Unfractionated heparin (UFH) was initiated during the acute
      period, but heparin-induced thrombocytopenia developed. Transition from UFH to
      fondaparinux resulted in successful anticoagulation for a period of platelet
      recovery. We report a case of HIT developing with a background of prothrombotic
      genetic risk factors and antiphospholipid syndrome. This case study highlights
      several difficulties in pediatric HIT cases.

PMID- 22964767
TI  - Clinical significance of the mixing test in laboratory diagnoses of lupus
      anticoagulant:  the fate of the mixing test in integrated lupus anticoagulant
      test systems.
AB  - The mixing test is used to determine the presence of inhibitors in laboratory
      diagnoses of lupus anticoagulant. Updated international guidelines state that an
      integrated lupus anticoagulant test system does not require the mixing test; an
      appraisal of the mixing tests in integrated lupus anticoagulant test systems is,
      therefore, required. We investigated the clinical relevance of mixing tests by
      using the best cutoff value of the mixing test through thrombotic risk analysis.
      A retrospective analysis was performed on 525 specimens with positive screening
      tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper
      venom (dRVVT) and silica clotting time. The diagnostic performance of two
      interpretation formulas (percentage correction, Rosner index) was assessed, and
      the thrombotic risk of a subgroup based on the mixing results was investigated.
      Finally, the thrombotic risk of lupus anticoagulant positivity based on the
      integrated lupus anticoagulant test system procedures was assessed for the
      appraisal of mixing test exclusion in integrated lupus anticoagulant test
      systems. The best cutoff values of mixing test interpretation methods based on
      dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index.
      There was no substantial difference in the thrombotic risk between percentage
      correction and the Rosner index. The mixing-positive group showed a higher lupus
      anticoagulant titer and higher thrombotic risk than the mixing-negative group.
      However, even the mixing-negative group carried a significant risk of thrombosis.
      Finally, lupus anticoagulant positivity determined by the updated two-step
      procedure (screening and confirmation tests) showed higher thrombotic risk than
      that determined by the traditional three-step procedure (screening, mixing, and
      confirmation tests). Although a positive mixing result can predict a high risk of
      thrombosis, negative mixing results are also associated with a substantial
      thrombotic risk. The updated two-step procedure without the mixing test is
      relevant for lupus anticoagulant detection in the context of thrombotic risk
      estimation.

PMID- 22964768
TI  - Diagnostic ultrasound activates pure prekallikrein.
AB  - Diagnostic ultrasound activates the contact phase of human coagulation. This has
      been seen in human blood or plasma or with purified factor 12. The present work
      aimed to quantify a possibly triggering action of ultrasound on purified
      prekallikrein, the second of the two main triggers of the intrinsic hemostasis
      cascade. Either 2.7 MUg/ml human prekallikrein or for control 1 MUg/ml kallikrein
      in 26% glycerol - 0.54% NaCl-10.6 mmol/l Na3 citrate pH 7.4, in emptied
      polypropylene coagulation monovettes (Sarstedt) were exposed to diagnostic
      ultrasound (Siemens Acouson Antares, 5 MHz, 0.6 TIB, 0.6 TIS) for 0-5 min at room
      temperature (RT). Fifty microliter samples were withdrawn in duplicate and placed
      into an U-wells high quality microtiter plate (Brand 781600). Then 10 MUl 2
      mmol/l chromogenic substrate HD-CHG-Ala-Arg-pNA in 0.45% NaCl were added, and the
      increase in absorbance with time (DeltaA405 nm /t at 37 degrees C) was determined
      by a microtiterplate photometer with a 1 mA resolution (PHOmo; anthos). Exposure
      to diagnostic ultrasound biphasically increased the chromogenic activity of a
      prekallikrein solution in 26% glycerol. About 3-4 min ultrasound at 23  degrees C
      generated about 0.02 MUg/ml kallikrein, that means that about 1% of pure
      prekallikrein in glycerol was converted into kallikrein. Thus, diagnostic
      ultrasound activates purified human prekallikrein to kallikrein. The ultrasound
      energy seems to fold the latent proenzyme prekallikrein into the active enzyme
      kallikrein. This contributes to explain the triggering action of ultrasound on
      the contact system of plasmatic human coagulation. Conversion of only 1% of
      prekallikrein into kallikrein is absolutely sufficient to start the intrinsic
      coagulation cascade. The clinical consequence of this action of ultrasound on
      intrinsic coagulation is that patients at risk for thrombosis, for example,
      patients with insufficiencies of hepatocytes, AT-3, C1-ina, or fibrinolysis
      should be protected by low-molecular-weight-heparin prior to the exposure of
      ultrasound, especially upon its prolonged exposure.

PMID- 22964769
TI  - Freezing does not decrease carbon monoxide-mediated hypercoagulation and
      hypofibrinolysis in human plasma.
AB  - Carbon monoxide (CO) has been demonstrated to enhance coagulation and attenuate
      fibrinolysis in vitro and in vivo. Hemostasis is affected by CO interactions with
      key heme-modulated molecules. We wished to determine whether freezing would
      affect CO-mediated changes in coagulation/fibrinolysis in plasma in anticipation
      of collecting samples both within our institution and from collaborating centers.
      Plasma was exposed to CO by addition of 0-100 MUmol/l
      tricarbonyldichlororuthenium (II) dimer, with a portion of plasma immediately
      frozen at -80  degrees C. Unfrozen plasma was subjected to thrombelastographic
      analysis following tissue factor activation, with some samples exposed to tissue
      type plasminogen activator. Frozen plasma was subsequently thawed and similarly
      analyzed. Freezing did not significantly change CO-mediated enhancement of
      coagulation or attenuation of fibrinolysis. Hemostatic changes in plasma exposed
      to CO are not affected by a freeze-thaw cycle, which will permit local batch
      processing of samples and transport of samples on dry ice from collaborating
      centers.

PMID- 22964770
TI  - Outcomes in women receiving low-molecular-weight heparin during pregnancy.
AB  - To assess the rate and type of maternal and infant complications among pregnant
      women receiving low-molecular-weight heparin (LMWH). Retrospective study of
      pregnant women on LMWH referred to two university hematology clinics from January
      2001 to December 2010. We recorded the number of pregnancies, indication, dose
      and dose adjustments for LMWH, pregnancy outcomes (live births, maternal and
      infant complications) and side effects of LMWH. There were 89 pregnancies in 76
      women. The most common indication for LMWH was a history of adverse outcome of
      pregnancy associated with thrombophilia. LMWH was adjusted in 75 and 45% of
      pregnancies in women on therapeutic and prophylactic doses, respectively. Live
      birth rate was 97%. There were 25 maternal and 11 infant complications. Side
      effects were minimal and included decreased bone mineral density and bleeding.
      LMWH use among pregnant women is associated with successful pregnancy outcomes.
      Although side effects were minimal, maternal and infant complications occurred in
      28 and 12% of cases, respectively.

PMID- 22964772
TI  - Drug-induced thrombocytopenia:  a less known interaction.
AB  - A 57-year-old woman with a left frontal lobe tumor was started on seizure
      prophylaxis with phenytoin and dexamethasone while awaiting elective surgery for
      tumor excision. Within a week, she developed a rash all over her body secondary
      to phenytoin hypersensitivity and her platelet counts decreased progressively to
      as low as 20,000/MUl. Phenytoin was discontinued and she was given intravenous
      immunoglobulin for 2 days. She had progressive recovery of the platelet count to
      her baseline over the next 6 days. This case of phenytoin-induced
      thrombocytopenia emphasizes the importance of recognizing thrombocytopenia
      secondary to drug use and also highlights a lesser known but important
      interaction between phenytoin and dexamethasone to enhance this effect. We also
      provide a brief review of the literature and comment on the pathophysiology of
      this rare condition.

PMID- 22964771
TI  - Novel microfluidic platform for automated lab-on-chip testing of
      hypercoagulability panel.
AB  - Current methods for hypercoagulability panel testing require large blood volumes
      and long turn-around testing times. A novel microfluidic platform has been
      designed to perform automated multiplexed hypercoagulability panel testing at
      near patient, utilizing only a single droplet of blood sample. We test the
      hypothesis that this novel platform could be utilized to perform specific
      multiplexed ELISA-based hypercoagulability panel testing for antithrombin III,
      protein C, protein S and factor VIII antigens, as well as anticardiolipin/human
      anti-beta2-glycoprotein-1 IgG antibodies--on blood samples. Sandwich ELISA was
      modified by utilizing magnetic beads coated with specific antibodies as the solid
      phase using fluorescence readout. Percentage recovery was calculated using four
      parameter logistic curves. On-chip ELISA with single factors was compared with
      multiplex factor ELISA for known concentrations of sample. Blood samples were
      analyzed on-chip and compared with traditional bench-top assays. Time for
      multiplexed performance of hypercoagulability panel ELISA on-chip with controls
      is 72 min. Recovery rates (range 80-120%) for known concentrations of specific
      factors was not significantly different when assays were performed using a single
      factor vs. multiplex factor analysis. Assay results were not significantly
      different between individual assays performed either on bench-top or on-chip with
      patient blood and/or plasma. Utilizing a novel digital microfluidic platform, we
      demonstrate the feasibility of automated hypercoagulability panel testing on
      small volume of plasma and whole blood patient samples with high fidelity.
      Further investigation is required to test the application of this novel
      technology at point-of-care clinical settings.

PMID- 22964773
TI  - Optically and thermally induced molecular switching processes at metal surfaces.
AB  - Using light to control the switching of functional properties of surface-bound
      species is an attractive strategy for the development of new technologies with
      possible applications in molecular electronics and functional surfaces and
      interfaces. Molecular switches are promising systems for such a route, since they
      possess the ability to undergo reversible changes between different molecular
      states and accordingly molecular properties by excitation with light or other
      external stimuli. In this review, recent experiments on photo- and thermally
      induced molecular switching processes at noble metal surfaces utilizing two
      photon photoemission and surface vibrational spectroscopies are reported. The
      investigated molecular switches can either undergo a trans-cis isomerization or a
      ring opening-closure reaction. Two approaches concerning the connection of the
      switches to the surface are applied: physisorbed switches, i.e. molecules in
      direct contact with the substrate, and surface-decoupled switches incorporated in
      self-assembled monolayers. Elementary processes in molecular switches at
      surfaces, such as excitation mechanisms in photoisomerization and kinetic
      parameters for thermally driven reactions, which are essential for a microscopic
      understanding of molecular switching at surfaces, are presented. This in turn is
      needed for designing an appropriate adsorbate-substrate system with the desired
      switchable functionality controlled by external stimuli.

PMID- 22964774
TI  - Electrical annealing and temperature dependent transversal conduction in
      multilayer reduced graphene oxide films for solid-state molecular devices.
AB  - The transversal conductance through thin multi-layered films of reduced graphene
      oxide was studied as a function of temperature in a solid-state device setup
      designed for molecular electronic measurements. Upon cooling to cryogenic
      temperatures, the resistivity of the films increased by about three orders of
      magnitude compared to the value at room temperature, and this temperature
      dependence was described by a variable range hopping model. Above a certain
      threshold voltage the films could be annealed electrically at low temperatures.
      This electrical annealing resulted in a dramatic decrease in resistivity by up to
      four orders of magnitude. Upon reheating, the conductivity of the annealed films
      displayed an almost negligible temperature dependence. These results are
      promising for the application of reduced graphene oxide as a soft top-contact
      layer for molecular monolayer devices in the solid-state.

PMID- 22964775
TI  - Effectiveness of cognitive-behavioral therapy addition to pharmacotherapy in
      resistant obsessive-compulsive disorder: a multicenter study.

PMID- 22964776
TI  - Synthesis and biological evaluation of a potent salicylihalamide A lactam
      analogue.
AB  - The first synthesis of a lactam analogue of salicylihalamide A (1) is reported. A
      key step in the approach was a photochemical acylation coupling between amine 10
      and dioxinone 9 to form the amide 19. Acetylation followed by RCM with Grubbs 1st
      generation catalyst gave the desired E-lactam 23 (E : Z ratio 87 : 13) as the
      major compound. Conversion of macrolactam 23 into the vinyl iodide 26 followed by
      Cu catalysed cross coupling with the diene amide 7 gave aza-salicylihalamide
      analogue 3 in good yield. This compound demonstrated potent activity against
      several human leukaemia cell lines.

PMID- 22964777
TI  - Impact of Angiotensin receptor blockers on Alzheimer disease neuropathology in a
      large brain autopsy series.
AB  - BACKGROUND Angiotensin II may be involved in amyloid metabolism in the brain.
      Angiotensin receptor blockers (ARBs) may also prevent cognitive decline.
      OBJECTIVE To evaluate the impact of treatment with ARBs on the neuropathology of
      Alzheimer disease (AD) in the National Alzheimer Coordinating Center database,
      which includes aggregated data and brain autopsies from 29 AD centers throughout
      the United States. DESIGN Multiple logistic regression was used to compare the
      pathologic findings in hypertensive subjects taking ARBs with those taking other
      antihypertensive treatments as well as with hypertensive subjects who did not
      receive antihypertensive medications. SETTING Neuropathologic data included
      neuritic plaque and neurofibrillary tangle measures and vascular injury markers.
      PATIENTS Data were collected from participants who were self-referred or provider
      referred and included those with and without cognitive disorders. Our sample
      included only hypertensive participants and excluded cognitively and
      neuropathologically normal participants (N = 890; mean age at death, 81 years
      [range, 39-107 years]; 43% women; 94% white). RESULTS Participants with or
      without AD who were treated with ARBs showed less amyloid deposition markers
      compared with those treated with other antihypertensive medications (lower
      Consortium to Establish a Registry of Alzheimer Disease score: odds ratio, 0.47,
      95% CI, 0.27-0.81; Alzheimer Disease and Related Disorders Association score:
      odds ratio, 0.43, 95% CI, 0.21-0.91; Braak and Braak stage: odds ratio, 0.52, 95%
      CI, 0.31-0.85; neuritic plaques: odds ratio, 0.59, 95% CI, 0.37-0.96). They also
      had less AD-related pathology compared with untreated hypertensive subjects.
      Participants who received ARBs were more likely to have had a stroke; hence, they
      had more frequent pathologic evidence of large vessel infarct and hemorrhage.
      CONCLUSION Treatment with ARBs is associated with less AD-related pathology on
      autopsy evaluations. The effect of ARBs on cognitive decline in those with
      dementia or AD needs further investigation.

PMID- 22964778
TI  - Interventions to improve adherence to self-administered medications for chronic
      diseases in the United States: a systematic review.
AB  - BACKGROUND: Suboptimum medication adherence is common in the United States and
      leads to serious negative health consequences but may respond to intervention.
      PURPOSE: To assess the comparative effectiveness of patient, provider, systems,
      and policy interventions that aim to improve medication adherence for chronic
      health conditions in the United States. DATA SOURCES: Eligible peer-reviewed
      publications from MEDLINE and the Cochrane Library indexed through 4 June 2012
      and additional studies from reference lists and technical experts. STUDY
      SELECTION: Randomized, controlled trials of patient, provider, or systems
      interventions to improve adherence to long-term medications and nonrandomized
      studies of policy interventions to improve medication adherence. DATA EXTRACTION:
      Two investigators independently selected, extracted data from, and rated the risk
      of bias of relevant studies. DATA SYNTHESIS: The evidence was synthesized
      separately for each clinical condition; within each condition, the type of
      intervention was synthesized. Two reviewers graded the strength of evidence by
      using established criteria. From 4124 eligible abstracts, 62 trials of patient-,
      provider-, or systems-level interventions evaluated 18 types of interventions;
      another 4 observational studies and 1 trial of policy interventions evaluated the
      effect of reduced medication copayments or improved prescription drug coverage.
      Clinical conditions amenable to multiple approaches to improving adherence
      include hypertension, heart failure, depression, and asthma. Interventions that
      improve adherence across multiple clinical conditions include policy
      interventions to reduce copayments or improve prescription drug coverage, systems
      interventions to offer case management, and patient-level educational
      interventions with behavioral support. LIMITATIONS: Studies were limited to
      adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and
      substance abuse) in the United States. Clinical and methodological heterogeneity
      hindered quantitative data pooling. CONCLUSION: Reduced out-of-pocket expenses,
      case management, and patient education with behavioral support all improved
      medication adherence for more than 1 condition. Evidence is limited on whether
      these approaches are broadly applicable or affect longterm medication adherence
      and health outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and
      Quality.

PMID- 22964779
TI  - Antiaging effects of simvastatin on vascular endothelial cells.
AB  - The anti-inflammatory, antioxidative, and antiarteriosclerosis activities of
      simvastatin along with its protective effects on the endothelium suggest that it
      may also have antiaging effects. The aim of this study was to investigate the
      antiaging effects of simvastatin as well as its effects on sirtuin 1 (SIRT1)
      expression in endothelial cells. Aged rats and human umbilical vein endothelial
      cells were treated with simvastatin in the presence and absence of oxidized low
      density lipoprotein (OX-LDL). Aortic beta-galactosidase staining was undertaken
      to determine senescence, and SIRT1 protein expression was evaluated using Western
      blot analysis. After simvastatin therapy, arterial endothelial cell aging was
      significantly reduced, and SIRT1 expression was significantly increased. The OX
      LDL significantly accelerated the senescence of umbilical vein endothelial cells
      and decreased SIRT1 expression. The OX-LDL-induced downregulation of SIRT1 was
      blocked by simvastatin. Simvastatin treatment also reduced umbilical vein
      endothelial cell aging and increased SIRT1 expression. 

PMID- 22964780
TI  - Increased thrombopoietin and mean platelet volume in patients with ischemic
      stroke.

PMID- 22964781
TI  - Plasma levels and distribution of gene polymorphisms of factor VII in Turkish
      population.
AB  - Three factor VII (FVII) promoter haplotypes are associated with stratified plasma
      FVII levels. To our knowledge, this is the first study examining the distribution
      of FVII gene polymorphism and levels in Turkish population. The study population
      was classified into 3 groups according to the absence of coronary arterial
      disease and presence or absence of a history of myocardial infarction. It was
      found that the levels of FVII coagulant activity (FVIIc) were higher in the event
      group than that of the other groups. Participants with high FVIIc levels were
      found to have 2-fold increased risk for myocardial infarction. The alleles at the
      FVII loci in all cases are similar. In conclusion, our results indicate that
      FVIIc levels have an important predictive role in cardiovascular events. The
      distribution of FVII gene polymorphisms in the Turkish population shows
      significant differences when compared with European populations. 

PMID- 22964782
TI  - Severe pediatric blunt trauma--successful ROTEM-guided hemostatic therapy with
      fibrinogen concentrate and no administration of fresh frozen plasma or platelets.
AB  - Use of allogeneic blood products to treat pediatric trauma may be challenged,
      particularly in relation to safety. We report successful treatment of a child
      with severe abdominal and pelvic injuries with preemptive fibrinogen
      supplementation followed by rotational thromboelastometry (ROTEM)-guided, goal
      directed hemostatic therapy. Fibrinogen concentrate was administered (total dose:
      2 g), while transfusion of fresh frozen plasma and platelet concentrate was
      avoided. Activated partial thromboplastin time was prolonged and Quick values
      were low but ROTEM clotting time values remained normal, therefore, no thrombin
      generating drugs were considered necessary. This case shows the potential for
      hemostatic treatment with coagulation factor concentrates to be applied to
      pediatric trauma. 

PMID- 22964784
TI  - Genetic alterations associated with progression and recurrence in meningiomas.
AB  - Meningiomas are the most common primary brain tumors; they arise from the
      coverings of the brain. Although meningiomas are generally benign, some are more
      clinically aggressive, as reflected by their histopathological features or by
      their unexpected recurrence. We hypothesized that recurrent histologically benign
      meningiomas might have genetic features in common with those showing a more
      aggressive histology. By comparing gene expression profiles associated with
      meningioma progression and recurrence in 128 tumor samples (i.e. 83 benign World
      Health Organization [WHO] Grade I, 37 atypical WHO Grade II, and 8 anaplastic WHO
      Grade III) from 121 patients, we identified a 49-gene signature of meningioma
      aggressivity. This signature classified the tumors into 2 groups showing
      different clinical and pathological behaviors. The signature was composed of
      genes involved in the cell cycle (TMEM30B, CKS2, and UCHL1) and other pathways
      previously described as being altered in meningiomas, that is, WNT (SFRP1 and
      SFRP4) and transforming growth factor-beta pathways (LTBP2 and LMO4). Overall,
      gene downregulation was observed in advanced and recurrent samples versus benign
      and original ones. We propose that this gene repression may be caused by gene
      promoter hypermethylation, as in the case of UCHL1 and SFRP1, suggesting that
      this epigenetic event, together with loss of specific chromosomal regions, may
      play an important role in meningioma progression and recurrence.

PMID- 22964785
TI  - Time course and spatial profile of Nogo-A expression in experimental autoimmune
      encephalomyelitis in C57BL/6 mice.
AB  - Inhibition of the myelin-associated neurite outgrowth inhibitor Nogo-A has been
      found to be beneficial in experimental autoimmune encephalomyelitis (EAE), but
      there are little data on its expression dynamics during the disease course. We
      analyzed Nogo-A mRNA and protein during the course of EAE in 27 C57BL/6 mice and
      in 8 controls. Histopathologic and molecular analyses were performed on Day 0
      (naive), preclinical (Day 10), acute (Days 18-22) and chronic (Day 50) time
      points. In situ hybridization and real-time polymerase chain reaction analyses
      revealed reduced Nogo-A mRNA expression at preclinical (p < 0.0001) and acute
      phases (p < 0.0001), followed by upregulation during the chronic phase (p <
      0.0001). Nogo-A mRNA was expressed in neurons and oligodendrocytes. By
      immunohistochemistry and Western blot, there was increased Nogo-A protein
      expression (p < 0.001) in the chronic phase. Moreover, spatial differences were
      observed within EAE lesions. The pattern of Nogo-A protein expression inversely
      correlated with axonal regeneration growth-associated protein 43-positive axons
      (60% of which were Nogo-A contact-free during the acute phase) and axonal injury
      (beta-amyloid precursor protein-positive axons). Cortical Nogo-66 receptor
      protein and mRNA levels increased during the chronic phase. The results indicate
      that Nogo-A and Nogo receptor are actively regulated in EAE lesions; this may
      indicate a specific time window for localized axonal regeneration in the acute
      phase of EAE.

PMID- 22964787
TI  - Toll-like receptors promote inflammation in idiopathic inflammatory myopathies.
AB  - The roles of Toll-like receptors (TLRs) and their myeloid differentiation
      response gene 88 (MyD88)-dependent and MyD88-independent signaling cascade
      particularly with regard to the pathogenesis and regulation of immune responses
      in idiopathic inflammatory myopathies are unclear. We investigated these pathways
      in muscle biopsies from 5 cases each of polymyositis, inclusion body myositis,
      dermatomyositis, vasculitis-associated interstitial myositis, and noninflammatory
      neurogenic atrophy. Toll-like receptor 2, TLR4, TLR9, and MyD88 mRNA transcripts
      and protein expression were increased in all subtypes of idiopathic inflammatory
      myopathies. Upregulation of MyD88 was associated with increased mRNA levels of
      interferon-gamma, interleukin 12p40, and interleukin 17, suggesting NF-kappaB
      activation via the MyD88-dependent pathway in early stages. The costimulatory
      molecules CD80 and CD86 were expressed on inflammatory infiltrates in idiopathic
      inflammatory myopathies and may additionally contribute to activation of the
      MyD88-independent pathway, leading to nuclear factor-kappaB activation in late
      stages. Our data suggest that nuclear factor-kappaB activation via both the MyD88
      dependent and the MyD88-independent pathways contributes to the proinflammatory
      milieu in idiopathic inflammatory myopathies.

PMID- 22964786
TI  - Motoneuron replacement for reinnervation of skeletal muscle in adult rats.
AB  - Reinnervation is needed to rescue muscle when motoneurons die in disease or
      injury. Embryonic ventral spinal cord cells transplanted into peripheral nerve
      reinnervate muscle and reduce atrophy, but low motoneuron survival may limit
      motor unit formation. We tested whether transplantation of a purified population
      of embryonic motoneurons into peripheral nerve (mean +/- SE, 146,458 +/- 4,011
      motoneurons) resulted in more motor units and reinnervation than transplantation
      of a mixed population of ventral spinal cord cells (72,075 +/- 12,329
      motoneurons). Ten weeks after either kind of transplant, similar numbers of
      neurons expressed choline acetyl transferase and/or Islet-1. Motoneuron numbers
      always exceeded the reinnervated motor unit count. Most motor end plate were
      simple plaques. Reinnervation significantly reduced muscle fiber atrophy. These
      data show that the number of transplanted motoneurons and motoneuron survival do
      not limit muscle reinnervation. Incomplete differentiation of motoneurons in
      nerve and lack of muscle activity may result in immature neuromuscular junctions
      that limit reinnervation and function.

PMID- 22964788
TI  - X-ray tomography using the full complex index of refraction.
AB  - We report on x-ray tomography using the full complex index of refraction recorded
      with a grating-based x-ray phase-contrast setup. Combining simultaneous
      absorption and phase-contrast information, the distribution of the full complex
      index of refraction is determined and depicted in a bivariate graph. A simple
      multivariable threshold segmentation can be applied offering higher accuracy than
      with a single-variable threshold segmentation as well as new possibilities for
      the partial volume analysis and edge detection. It is particularly beneficial for
      low-contrast systems. In this paper, this concept is demonstrated by experimental
      results.

PMID- 22964789
TI  - Reduced anticipatory dopamine responses to food in rats exposed to high fat
      during early development.
AB  - We have previously demonstrated that exposure to high fat (HF) during early
      development alters the presynaptic regulation of mesolimbic dopamine (DA), and
      increases incentive motivation for HF food rewards. The goal of the present
      experiments was to examine the long-term consequences of early exposure to HF on
      anticipatory and consumatory nucleus accumbens (NAc) DA responses to HF food
      rewards. Mothers were maintained on a HF (30% fat) or control diet (CD; 5% fat)
      from gestation day 13 to postnatal day 22 when offspring from both diet groups
      were weaned and maintained on the CD until adulthood. In vivo NAc DA responses to
      food anticipation and consumption were measured in a Pavlovian conditioning
      paradigm using voltammetry in freely moving rats. HF-exposed offspring displayed
      reduced NAc DA responses to a tone previously paired with the delivery of HF food
      rewards. In an unconditioned protocol, consumatory NAc DA responses could be
      isolated, and were similar in HF and control offspring. These data demonstrate
      that exposure to HF through maternal diet during early development might program
      behavioral and functional responses associated with mesolimbic DA
      neurotransmission, thus leading to an increased HF feeding and obesity.

PMID- 22964790
TI  - Increased adipose tissue hypoxia and capacity for angiogenesis and inflammation
      in young diet-sensitive C57 mice compared with diet-resistant FVB mice.
AB  - OBJECTIVE: High-fat diets (HFDs) result in increased body weight. However, this
      is not uniform and determining the factors that make some animals or individual
      more susceptible to this diet-induced weight gain is a critical research
      question. The expansion of white adipose tissue (WAT) associated with weight gain
      requires high rates of angiogenesis to support the expanding tissue mass. We
      hypothesized that diet-induced obese (DIO) mice have a greater capacity for WAT
      angiogenesis and remodeling than diet-resistant (DR) mice at a young age, before
      age or DIO. DESIGN: We measured body weight and body composition by nuclear
      magnetic resonance. We compared the expression of genes related to lipid
      metabolism, angiogenesis and inflammation by real-time, quantitative PCR and PCR
      arrays. WAT morphology and distribution of adipocyte size were analyzed. The
      level of hypoxia and vascular density was assessed by immunohistochemistry in WAT
      of young mice. RESULTS: C57Bl/6 mice were DIO and FVB/N (FVB) mice DR after 8
      weeks on a low-fat diet or HFD. However, C57Bl/6 mice had lower body weight,
      lower adiposity, smaller adipocytes and decreased leptin and lipogenic genes
      expression in adipose tissue than FVB mice at 9 weeks of age on a chow diet.
      Despite having smaller adipocytes, the level of hypoxia and the expression of pro
      angiogenesis genes were higher in WAT of young C57Bl/6 mice than young FVB mice.
      In addition, expression of genes related to macrophages and their recruitment,
      and to proinflammatory cytokines, was significantly higher in WAT of young
      C57Bl/6 mice than young FVB mice. CONCLUSION: These data suggest that the
      potential for WAT remodeling in early period of growth is higher in C57Bl/6 mice
      as compared with FVB mice, and we hypothesize that it may contribute to the
      increased susceptibility to DIO of C57Bl/6 mice.

PMID- 22964792
TI  - Fighting obesity or obese persons? Public perceptions of obesity-related health
      messages.
AB  - OBJECTIVE: This study examined public perceptions of obesity-related public
      health media campaigns with specific emphasis on the extent to which campaign
      messages are perceived to be motivating or stigmatizing. METHOD: In summer 2011,
      data were collected online from a nationally representative sample of 1014
      adults. Participants viewed a random selection of 10 (from a total of 30)
      messages from major obesity public health campaigns from the United States, the
      United Kingdom and Australia, and rated each campaign message according to
      positive and negative descriptors, including whether it was stigmatizing or
      motivating. Participants also reported their familiarity with each message and
      their intentions to comply with the message content. RESULTS: Participants
      responded most favorably to messages involving themes of increased fruit and
      vegetable consumption, and general messages involving multiple health behaviors.
      Messages that have been publicly criticized for their stigmatizing content
      received the most negative ratings and the lowest intentions to comply with
      message content. Furthermore, messages that were perceived to be most positive
      and motivating made no mention of the word 'obesity' at all, and instead focused
      on making healthy behavioral changes without reference to body weight.
      CONCLUSION: These findings have important implications for framing messages in
      public health campaigns to address obesity, and suggest that certain types of
      messages may lead to increased motivation for behavior change among the public,
      whereas others may be perceived as stigmatizing and instill less motivation to
      improve health.

PMID- 22964791
TI  - Associations between maternal prepregnancy body mass index and child
      neurodevelopment at 2 years of age.
AB  - OBJECTIVE: Both underweight and obese mothers have an increased risk for adverse
      offspring outcomes. Few studies have examined the association between
      prepregnancy body mass index (BMI) and children's neurodevelopment. SUBJECTS: We
      used data from the nationally representative Early Childhood Longitudinal Study
      Birth Cohort (ECLS-B; n=6850). Children were classified according to their
      mother's prepregnancy BMI (kg m(-2)) status: underweight (BMI <18.5), normal
      weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese class I (BMI 30.0
      34.9), and obese class II and III (BMI >=35.0). Children's age-adjusted mental
      development index (MDI) and psychomotor development index (PDI) T-scores (mean
      50, s.d. 10) were obtained using a validated shortened version of the Bayley
      Scales of Infant Development-II at approximately 2 years of age. While adjusting
      for sociodemographics, we estimated the average MDI and PDI scores or the risk of
      delayed (<-1 s.d. vs >1 s.d.) mental or motor development, relative to children
      of normal weight mothers. RESULTS: Compared with children of normal weight
      mothers, MDI scores were lower among children of mothers of all other
      prepregnancy BMI categories, with the greatest adjusted difference among children
      of class II and III obese mothers (-2.13 (95% CI -3.32, -0.93)). The adjusted
      risk of delayed mental development was increased among children of underweight
      (risk ratio (RR) 1.36 (95% CI 1.04, 1.78)) and class II and III obese (RR 1.38
      (95% CI 1.03, 1.84)) mothers. Children's PDI scores or motor delay did not differ
      by maternal prepregnancy BMI. CONCLUSION: In this nationally representative
      sample of 2-year-old US children, low and very-high maternal prepregnancy BMI
      were associated with increased risk of delayed mental development but not motor
      development.

PMID- 22964794
TI  - A prospective study of rollerball endometrial ablation in the management of
      refractory recurrent symptomatic endometrial hyperplasia without atypia.
AB  - BACKGROUNDS: Menorrhagia - heavy, extended or irregular menstruations - may be
      associated with endometrial hyperplasia. The aim of this study was to evaluate
      the clinical efficacy and safety of transcervical rollerball endometrial ablation
      (EA-R) and to discuss surgical outcomes in patients with simple endometrial
      hyperplasia without atypia who have had a history of medical treatment failure or
      recurrence. METHODS: A prospective study was designed. Thirty women underwent EA
      R. Preoperative and postoperative menstrual status, sexual activity, and
      satisfaction with the procedure were assessed. Complications, clinical outcomes,
      and need for re-intervention were evaluated. RESULTS: No major complications
      occurred. All patients were discharged from hospital within 24 h. A reduction of
      menorrhagia was observed in patients as follows: 17 patients (56.67%) had
      amenorrhea, 10 (33.33%) hypomenorrhea, and 2 (6.67%) eumenorrhea. Hysterectomy
      was performed only in 1 patient who was unresponsive to ablation treatment.
      CONCLUSIONS: In selected patients who have persistent uterine bleeding not
      responsive to conservative therapy, low risk for future endometrial cancer, and
      wish to retain their uterus, EA-R treatment is safe, effective, and might be an
      alternative to hysterectomy with good toleration and high rate of patient
      satisfaction. The advantages of EA-R include low incidence of complications,
      lower morbidity, shorter hospitalization, and faster recovery.

PMID- 22964793
TI  - The role of obesity, different fat compartments and sleep apnea severity in
      circulating leptin levels: the Icelandic Sleep Apnea Cohort study.
AB  - OBJECTIVES: To assess whether sleep apnea severity has an independent
      relationship with leptin levels in blood after adjusting for different measures
      of obesity and whether the relationship between obstructive sleep apnea (OSA)
      severity and leptin levels differs depending on obesity level. METHODS: Cross
      sectional study of 452 untreated OSA patients (377 males and 75 females), in the
      Icelandic Sleep Apnea Cohort (ISAC), age 54.3+/-10.6 (mean+/-s.d.), body mass
      index (BMI) 32.7+/-5.3 kg m(-2) and apnea-hypopnea index 40.2+/-16.1 events per
      h. A sleep study and magnetic resonance imaging of abdominal visceral and
      subcutaneous fat volume were performed, as well as fasting serum morning leptin
      levels were measured. RESULTS: Leptin levels were more highly correlated with
      BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se.
      No relationship was found between sleep apnea severity and leptin levels,
      assessed within three BMI groups (BMI <30, BMI 30-35 and BMI > or =35 kg m(-2)).
      In a multiple linear regression model, adjusted for gender, BMI explained 38.7%
      of the variance in leptin levels, gender explained 21.2% but OSA severity did not
      have a significant role and no interaction was found between OSA severity and BMI
      on leptin levels. However, hypertension had a significant effect on the
      interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for
      nonhypertensive OSA subjects (n=249), the association between leptin levels and
      OSA severity explained a minor but significant variance (3.2%) in leptin levels.
      This relationship was greatest for nonobese nonhypertensive subjects (significant
      interaction with obesity level). No relationship of OSA severity and leptin
      levels was found for hypertensive subjects (n=199). CONCLUSION: Obesity and
      gender are the dominant determinants of leptin levels. OSA severity is not
      related to leptin levels except to a minor degree in nonhypertensive nonobese OSA
      subjects.

PMID- 22964796
TI  - Effects of electron-vibration coupling in transport through single molecules.
AB  - Using scanning tunneling spectroscopy, we study the transport of electrons
      through C(60) molecules on different metal surfaces. When electrons tunnel
      through a molecule, they may excite molecular vibrations. A fingerprint of these
      processes is a characteristic sub-structure in the differential conductance
      spectra of the molecular junction reflecting the onset of vibrational excitation.
      Although the intensity of these processes is generally weak, they become more
      important as the resonant character of the transport mechanism increases. The
      detection of single vibrational levels crucially depends on the energy level
      alignment and lifetimes of excited states. In the limit of large current
      densities, resonant electron-vibration coupling leads to an energy accumulation
      in the molecule, which eventually leads to its decomposition. With our
      experiments on C(60) we are able to depict a molecular scale picture of how
      electrons interact with the vibrational degrees of freedom of single molecules in
      different transport regimes. This understanding helps in the development of
      stable molecular devices, which may also carry a switchable functionality.

PMID- 22964795
TI  - Absence of functional LIN28B mutations in a large cohort of patients with
      idiopathic central precocious puberty.
AB  - AIM: To investigate LIN28B gene variants in children with idiopathic central
      precocious puberty (CPP). PATIENTS AND METHODS: We studied 178 Brazilian children
      with CPP (171 girls, 16.8% familial cases). A large multiethnic group (1,599
      subjects; Multiethnic Cohort, MEC) was used as control. DNA analysis and
      biochemical in vitro studies were performed. RESULTS: A heterozygous LIN28B
      variant, p.H199R, was identified in a girl who developed CPP at 5.2 years. This
      variant was absent in 310 Brazilian control individuals, but it was found in the
      same allele frequency in women from the MEC cohort, independent of the age of
      menarche. Functional studies revealed that when ectopically expressed in cells,
      the mutant protein was capable of binding pre-let-7 microRNA and inhibiting let-7
      expression to the same extent as wild-type Lin28B protein. Other rare LIN28B
      variants (p.P173P, c.198+ 32_33delCT, g.9575731A>C and c.-11C>T) were identified
      in CPP patients and controls. Therefore, no functional mutation was identified.
      CONCLUSION: In vitro studies revealed that the rare LIN28B p.H199R variant
      identified in a girl with CPP does not affect the Lin28B function in the
      regulation of let-7 expression. Although LIN28B SNPs were associated with normal
      pubertal timing, rare variations in this gene do not seem to be commonly involved
      in the molecular pathogenesis of CPP.

PMID- 22964797
TI  - Quantum dynamics study of the Cl + CH4 -> HCl + CH3 reaction: reactive resonance,
      vibrational excitation reactivity, and rate constants.
AB  - A quantum reactive dynamics, six-degrees-of-freedom, time-dependent wavepacket
      propagation method is applied to study the Cl + CH(4)    -> HCl + CH(3) reaction
      on the newly published potential energy surface by Czako and Bowman [Science,
      2011, 334, 343; J. Chem. Phys., 2012, 136, 044307]. We confirm not only the
      experimental speculation of the reactive resonance by observing a prominent
      resonance peak on the ground state reaction probability, but also the
      experimental and quasi-classical trajectory finding that at lower total
      scattering energy the translational energy drives the reactivity more than the
      vibrational energy for this late barrier reaction. The vibrational motions of
      CH(4) enhance the reactivity, and the C-H stretching motion has the biggest
      impact on the reactivity. The vibrational energy overall plays a more efficient
      role in the reactivity than the translational energy except at the lower
      scattering energy. The energy-shift approximation is employed to obtain an
      approximate full-dimensional cumulative reaction probability based on the six
      dimensional calculation. The calculated thermal rate coefficients agree very well
      with experimental measurements after using experimental vibrational frequencies
      and zero point energy to correct the reactant vibrational partition function and
      to convert the energy for the full dimensional cumulative reaction probability.

PMID- 22964798
TI  - Thick-tissue bioreactor as a platform for long-term organotypic culture and drug
      delivery.
AB  - We have developed a novel, portable, gravity-fed, microfluidics-based platform
      suitable for optical interrogation of long-term organotypic cell culture. This
      system is designed to provide convenient control of cell maintenance, nutrients,
      and experimental reagent delivery to tissue-like cell densities housed in a
      transparent, low-volume microenvironment. To demonstrate the ability of our Thick
      Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density
      cellular arrays, we observed the morphogenic growth of human mammary epithelial
      cell lines, MCF-10A and their invasive variants, cultured under three-dimensional
      (3D) conditions inside our system. Over the course of 21 days, these cells
      typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel.
      This complex morphogenic process requires alterations in a variety of cellular
      functions, including degradation of extracellular matrix that is regulated by
      cell-produced matrix proteinases. For our "drug" delivery testing and validation
      experiments we have introduced proteinase inhibitors into the fluid supply
      system, and we observed both reduced proteinase activity and inhibited cellular
      morphogenesis. The size inhibition results correlated well with the overall
      proteinase activities of the tested cells.

PMID- 22964800
TI  - Combination of tramadol with minocycline exerted synergistic effects on a rat
      model of nerve injury-induced neuropathic pain.
AB  - Neuropathic pain is a refractory clinical problem. Certain drugs, such as
      tramadol, proved useful for the treatment of neuropathic pain by inhibiting the
      activity of nociceptive neurons. Moreover, studies indicated that suppression or
      modulation of glial activation could prevent or reverse neuropathic pain, for
      example with the microglia inhibitor minocycline. However, few present clinical
      therapeutics focused on both neuronal and glial participation when treating
      neuropathic pain. Therefore, the present study hypothesized that combination of
      tramadol with minocycline as neuronal and glial activation inhibitor may exert
      some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain.
      Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in
      a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression
      was downregulated by intrathecal tramadol or minocycline. Combination of tramadol
      with minocycline exerted powerful and synergistic effects on SNL-induced
      neuropathic pain also in a dose-dependent manner. Moreover, the drug combination
      enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42
      expression, compared to either drug administered alone. These results indicated
      that combination of tramadol with minocycline could exert synergistic effects on
      peripheral nerve injury-induced neuropathic pain; thus, a new strategy for
      treating neuropathic pain by breaking the interaction between neurons and glia
      bilaterally was also proposed.

PMID- 22964801
TI  - Lysozyme-silica hybrid materials: from nanoparticles to capsules and double
      emulsion mineral capsules.
AB  - Alterations in the synthesis methodology concerning emulsion templated
      biocatalyzed silicification provide control over the morphology of SiO(2)-hybrid
      structures.

PMID- 22964802
TI  - Compulsory commitment to care of substance misusers: international trends during
      25 Years.
AB  - PURPOSE: The study explores international trends in law on compulsory commitment
      to care of substance misusers (CCC), and two subtypes - civil CCC and CCC within
      criminal justice legislation - as well as maximum length and amount of
      applications of such care. METHOD: The time period covers more than 25 years, and
      a total of 104 countries and territories. The study is based on available data in
      three times of observation (1986, 1999 and 2009). Applications of CCC in number
      of cases are studied on European level for the years 2002-2006. Trends are
      analyzed using nonparametric tests and general linear models for repeated
      measures. Findings are discussed from contextual analysis. RESULT: There is a
      trend towards decrease in the number of countries worldwide having civil CCC
      legislation after the millennium, while CCC under criminal law has increased
      since the mid-1980s, resulting in some total net decrease. The shift results in
      longer mean duration of CCC and an increase in the number of cases sentenced.
      CONCLUSION: There is a risk that the shift from civil CCC to penal CCC implies
      more focus on young out-acting males in compulsory treatment and that the
      societal responsibility for more vulnerable persons might be neglected.

PMID- 22964803
TI  - The curriculum and education of medicine after Galen in Alexandria, Egypt.
AB  - In the medieval history of Islamic medicine sources, there is a lot of
      information regarding the translation of the books on the Alexandria Medical
      School and regarding the bibliographies of doctors.  Among the books that were
      taught in Alexandria Medical School, Galen's works are the most important. One of
      the famous translators, Hunayn ibn Ishaq, has made a full bibliographic list of
      Galen's works. Galen's corpus consisted of 16 books in summary. This corpus is
      called 'Jawami al-Iskandaraniyyin'. These books consisted of 7 training stages.
      The data on our research show that this corpus that was brought together during
      the last period of the Alexandria Medical School has been passed on to the
      Muslims as a whole, and has continued to be taught in a way according to the old
      traditions.

PMID- 22964804
TI  - Serum and urine boron and selenium levels in children with resistant epilepsy.
AB  - OBJECTIVE: To determine the role of serum and urine selenium, and boron levels in
      children with resistant epilepsy. METHODS: Serum and urine boron and selenium
      levels were studied in 53 cases (32 boys and 21 girls) diagnosed with resistant
      epilepsy between April 2006 and February 2007 at the Department of Pediatric
      Neurology, Erciyes University, Kayseri, Turkey.  Differences between groups were
      assessed using Student's t-test. Countable data were defined as percentage. Inter
      group difference was assessed by Chi-square test. P-values less than 0.05 were
      considered significant. RESULTS: When serum and urine boron and selenium levels
      were evaluated and compare with controls, a statistically significant difference
      was found in serum selenium, urine selenium, and urine boron levels (p<0.05). No
      significant difference was found in serum boron levels (p>0.05). CONCLUSION: It
      was observed that there is a need for selenium supplementation in treatment of
      patients with resistant epilepsy, while no etiologic role is observed for boron.

PMID- 22964805
TI  - Effect of dexamethasone on incidence of headache after spinal anesthesia in
      cesarean section.  A single blind randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of dexamethasone in reducing the incidence
      of headache. METHODS: This randomized controlled trial was carried out in 160
      cesarean patients with physical conditions-1 and emergency-1 at 22-Bahman
      Hospital, Iran between March 2010 and March 2011. Patients were randomly divided
      into sample and control groups. The women were studied for incidence of headache
      in the first 24 hours and the first week after spinal anesthesia. The mean
      severity of    the headache was evaluated on a quantitative scale using the
      visual analog scale (VAS). Data were gathered and analyzed using the SPSS
      software Version 11.5, descriptive statistical test, Chi-square, and Mann-Whitney
      U test. RESULTS: The incidence of post-dural puncture headache was observed in
      2.5% of the sample group and 12.5% of the control group in the first 24 hours
      after surgery (p=0.016); and 11.3% in the sample group and 32.5% in the control
      group in the first week after surgery (p=0.001). CONCLUSION: The findings of this
      research illustrate that intravenous dexamethasone reduces the incidence of post
      dural puncture headache in the first 24 hours and the first week after spinal
      anesthesia in cesarean section patients.

PMID- 22964806
TI  - Comparative efficacy of thiazolidinediones and metformin for polycystic ovary
      syndrome.
AB  - OBJECTIVE: To compare the efficacy of thiazolidinediones (TZDs) and metformin in
      polycystic ovary syndrome (PCOS) patients. METHODS: This systematic review study
      was conducted at Shengjing Hospital of China Medical University, Shenyang, China
      between January and February 2012. We searched the following databases MEDLINE,
      EMBASE, the Cochrane Library, and Chinese National Knowledge Infrastructure until
      January 2012. RESULTS: Six randomized controlled trials records involving 267
      patients were retrieved. The effect of TZDs on body mass index (BMI) was
      significantly lower than metformin (p=0.001; standardized mean difference [SMD] =
      0.40, 95% confidence interval [CI]; 0.16-0.65). The effect of TZDs on the
      Homeostasis Model of Assessment-Insulin Resistance Index was not significantly
      different from metformin (p=0.955, SMD = 0.01, 95% CI: -0.38-0.40). The effect of
      TZDs on the androgen level was not significantly different from metformin (serum
      total testosterone: p=0.287, SMD = 0.20, 95% CI: -0.17-0.57). CONCLUSION:
      Compared to metformin, TZDs had the same effectiveness in treating insulin
      sensitivity and lowering androgen in PCOS patients, but the effect on weight loss
      was not as good as metformin.

PMID- 22964807
TI  - Fistula plug versus conventional surgical treatment for anal fistulas.  A system
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate the recurrence and fecal incontinence of anal fistula plug
      versus conventional surgical treatment for anal fistulas. METHODS: This meta
      analysis was carried out in the General Surgery Department of the Second
      Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. We
      searched the Medline, EMBASE, and Cochrane Library from June 2011 to April 2012.
      The literature searches were carried out using medical subject headings and free
      text word: anal fistula, fibrin adhesive, fibrin sealant, and fistula plug.
      RESULTS: Two randomized controlled trials and 3 retrospective controlled studies
      were included. A total of 428 patients were included in our study. The recurrence
      rate was higher in those patients who accept fistula plug treatment (62.1% versus
      47%) (p=0.004). CONCLUSION: Anal fistula plug has a moderate probability of
      success with little risk of incontinence, but the recurrence rate is
      significantly higher than the conventional surgical treatment. This treatment is
      minimally invasive, repeatable, and sphincter-sparing. This meta-analysis failed
      to find a statistically significant difference in incontinence rate between
      conservative treatment and conventional surgical treatment.

PMID- 22964808
TI  - Evaluation of non-urgent visits to a busy urban emergency department.
AB  - OBJECTIVE: To identify the proportion of patients who were taken into the
      emergency room on the basis of legal regulations and non-urgent medical
      procedures. METHODS: This prospective study was conducted in the Emergency
      Department, Toros State Hospital, Mersin, Turkey. Data were collected over 4
      weeks (January 2011) and then analyzed using the Kolmogorov-Smirnov, Analysis of
      Variance, and Kruskal-Wallis H tests. RESULTS: During the study period, 21,014
      patients visited the Emergency Department. The applications were measured during
      a 3-shift schedule (08-16, 16-00, 00-08 hours). The total number of ordinary
      emergency admissions was 16,370. Of the total, 4,644   (22.1%) of the visits were
      evaluated as inappropriate. According to our study, inappropriate use of the
      emergency department was 51.1% more frequent during the 08-16 hours shift than
      the others. CONCLUSION: Inappropriate use of EDs with non-urgent applications
      makes it difficult to guarantee access for real emergency cases, decreases the
      readiness for care, and produces negative spillover effects on the quality of
      emergency services.

PMID- 22964809
TI  - Henoch-Schonlein purpura in children from the eastern province of Saudi Arabia.
AB  - OBJECTIVE: To evaluate the epidemiological and clinical profile of children with
      Henoch-Schonlein purpura (HSP) in eastern Saudi Arabia during a 15-year period.
      METHODS: The medical records of children discharged with a diagnosis of HSP from
      King Fahad Hospital of the University, Al-Khobar, Saudi Arabia, between January
      1996, and December 2010, were reviewed retrospectively. RESULTS: Of 78 patients,
      46 (59%) were boys, with a male to female ratio of 1.4:1. The patients' ages
      ranged from 22 months to 12 years, with a mean of 6.3 years. Approximately 60% of
      cases were presented during autumn and winter. Upper respiratory tract infection
      preceded HSP in over half of the patients and antistreptolyzin O (ASO) titer was
      positive in 11 of the 24 (46%) children tested at presentation. The main clinical
      features included skin purpura (100%), arthritis or arthralgia (66%),
      gastrointestinal manifestation (47%), orchitis (15%) of boys, and nephritis
      (24%). One patient with severe nephritis developed pulmonary hemorrhage and acute
      respiratory distress syndrome. Eleven (14%) patients received corticosteroid
      therapy. All children made a full recovery, only one patient with nephritis
      continued to have hypertension at 2 years follow up. Symptoms recurred in 6
      (7.7%) patients over a period ranging from one month to 2 years. CONCLUSION:
      Henoch-Schonlein purpura is a mild disease in the eastern province of Saudi
      Arabia and with no significant differences in the epidemic and clinical profile
      than that reported elsewhere.

PMID- 22964810
TI  - Incidence, types, geographical distribution, and risk factors of congenital
      anomalies in Al-Ramadi Maternity and Children's Teaching Hospital, Western Iraq.
AB  - OBJECTIVE: To study the incidence, types, geographical distribution, and risk
      factors of congenital anomalies (CAs) in a teaching hospital. METHODS: A total of
      5864 neonates were examined for CAs between October 2010 and October 2011 in Al
      Ramadi Maternity and Children's Teaching Hospital, Al-Ramadi, Western Iraq. Data
      include: neonate's name, gender, weight, and type of CAs, mother's age,
      residence, education, parity, consanguinity, smoking, illness, drugs, and
      ultrasound (U/S) results, father's age and smoking, and family recurrence of CAs.
      For every case, 2 controls were selected. Types and incidence of CAs was
      calculated. Odds ratio and confidence interval was utilized for risk factors
      evaluation. RESULTS: Overall CA incidences were 40.5/1000 for total births,
      40.8/1000 live births, and 270.0/1000 for stillbirths. Twenty percent of CAs was
      found as multiple, 80% single, 63.8% major, and 36.2% minor. The cardiovascular
      system was found most affected, followed by genito-urinary system. Low birth
      weight, male gender, maternal smoking, consanguinity, parity, and CAs family
      recurrence were found to be significant risk factors, and oligohydramnios,
      polyhydramnios, and positive CAs by U/S, found as significant co-factors
      associated with CAs, while parental age, and maternal education were not
      considered risk factors. CONCLUSION: Although the incidence of CAs was lower than
      the Al-Fallujah rate, it is still higher than many developed and developing
      countries. Amniotic fluid volume changes in U/S may hide an ominous CA, and
      maternal smoking exposure during pregnancy and consanguinity may expose the
      family to  a congenitally anomalous delivery.

PMID- 22964811
TI  - Prevalence of herpes simplex types 1 and 2, varicella zoster virus,
      cytomegalovirus, immunoglobulin G antibodies among female university students in
      Syria.
AB  - OBJECTIVE: To examine the current seroepidemiology of immunoglobulin (Ig)G for
      herpes simplex virus types 1 and 2 (HSV 1-2), varicella zoster virus (VZV), and
      cytomegalovirus (CMV) among university females of childbearing age in Syria.
      METHODS: A cross-sectional study was conducted to examine the female students of
      the Pharmacy College, Kalamoon University, Deratiah, Syria, where 316 sera were
      collected from October 2009 to November 2010, and subjected to HSV 1-2, VZV, and
      CMV IgG screening and titration using enzyme-linked immunosorbent assay-based
      techniques in the Microbiology Laboratory. RESULTS: A total of 164 participants
      were positive for HSV 1-2 IgG giving a prevalence of 52%, leaving a relatively
      high proportion of susceptibility among the tested group. For VZV, 91% of the
      participants (n=287) were positive for its specific IgG, while, regarding CMV,
      74.5% (n=235) were positive, and 25.5% were negative for CMV specific IgG.
      CONCLUSION: Although most participants were seropositive for herpes viruses IgG,
      suggesting a natural virus circulation within the community, screening for
      protective immunity is suggested against HSV, since a relatively high proportion
      of tested females are still susceptible. In addition, and because of its nasty
      outcomes during pregnancy, IgG against CMV should also be tested. High percentage
      of positivity towards VZV could be explained due to introduction of the new 
      vaccine program, and therefore, further analysis during pregnancy is not
      recommended.

PMID- 22964812
TI  - Alexithymia among Arab mothers of disabled children and its correlation with 
      mood disorders.
AB  - OBJECTIVE: To study alexithymia among mothers with disabled children in Saudi
      Arabia, and to explore if alexithymia is associated to their mood difficulties,
      and certain demographic variables. METHODS: We conducted a prospective study
      during January 2011 to April 2012, on 86 mothers (study group) caring for
      children with physical, mental, or sensory disabilities treated at a major
      tertiary rehabilitation hospital in Riyadh, Saudi Arabia. A total of 32 mothers
      (control group) with healthy children were also included. The Hospital Anxiety
      and Depression Scale (HADS) was used to measure the mood symptoms of mothers. The
      Toronto Alexithymia Scale (TAS-20) was administered to assess the degree of
      alexithymia. The demographic data of mothers and children were also collected.
      RESULTS: The mean age of children with a disability was 5.6.+/-3.1, and for
      healthy children was 6.3+/-3.7 (range 1-14) years. The mean age of mothers in the
      study group (n=86) was 33.9+/-6.1, and in the control group (n=32) was 35.2+/-7.3
      years. Mothers of children with disabilities had a significantly higher degree of
      alexithymia (p=0.001) and a significantly higher mean score of HADS-anxiety
      (p=0.042) and HADS-depression (p=0.021). Alexithymia had a significant
      correlation with mother's depression (p=0.0001) and anxiety (p=0.0001). No
      significant correlations were found between alexithymia and child's age
      (p=0.303), duration of disability (p=0.0941), and mother's age (p=0.235).
      CONCLUSION: Mothers caring for disabled children have higher features of
      alexithymia, and this is correlated to their elevated mood problems. Clinical
      implications are discussed.

PMID- 22964813
TI  - Knowledge, attitudes, and resources of sex education among female adolescents in
      public and private schools in Central Saudi Arabia.
AB  - OBJECTIVE: To investigate the knowledge and sources of knowledge among Saudi
      female adolescent students, attending public and private schools in the city of
      Riyadh with regard to sexuality and reproductive health. METHODS: This cross
      sectional survey was conducted from January to April 2009. Female adolescents
      between 11 and 21 years of age were invited to participate in the survey. Five
      classes of intermediate and secondary levels were randomly selected from 2   
      schools in Riyadh city. A total of 417 female students were included into the
      sample. Students were asked to answer a self-administrated questionnaire.
      RESULTS: Forty-two percent of the participants reported that they discussed
      sexual matters with their friends. Only 15.8% discussed these matters with their
      parents (mothers). Interestingly, 17.3% discussed sexual matters with the
      domestic helper. Most (61%) reported that their teachers had negative attitudes
      toward questions related to sexual issues. Only 33.3%, 37.9% and 14.5% knew that
      syphilis, gonorrhea, and hepatitis B, are sexually transmitted diseases. No
      significant differences were found between students in private schools and public
      schools. CONCLUSION: Formal sexual education should be introduced in the
      curriculum of the schools within the context of our religion and culture. Parents
      and teachers should be more open to discuss sexual issues with their children and
      students.

PMID- 22964814
TI  - Epstein-Barr virus associated smooth muscle tumors.  Synchronous liver and lung
      involvement.
AB  - Epstein-Barr virus associated smooth muscle tumors (EBV-SMT) are rare neoplasms
      that can occur in various anatomical locations. They mainly affect
      immunocompromised patients, and their clinical presentation is variable depending
      on size and organ involvement. They can pose diagnostic challenges, therefore if
      they are not considered in the differential diagnosis, they can be definitely
      misdiagnosed. Synchronous and multifocal involvement has been reported. Although
      malignant behavior maybe rarely seen; most behave in a benign fashion with
      favorable clinical outcome. We herein report an unusual case of synchronous EBV
      SMT that occurred in the lung and liver in a 44-year-old female patient 7 years
      after renal transplantation. Both lesions were histologically examined revealing
      benign appearing spindle cell neoplasm that was positive on immunohistochemical
      staining for smooth muscle actin, desmin, and caldesmon with strong nuclear
      staining for EBV RNA by in situ hybridization. A brief pertinent literature 
      review and discussion of EBV-SMT pathogenesis is offered.

PMID- 22964815
TI  - A rare case of primary rectal adenocarcinoma metastatic to the breast.
AB  - Primary rectal adenocarcinoma metastatic to the breast is an exceedingly rare
      event. Its management differs from that of primary breast cancer, as illustrated
      by this case. A 63-year-old woman presented with a breast lump 30 months after
      abdominoperineal resection for rectal adenocarcinoma, stage T3N1M0 (stage III),
      followed by standard postoperative radiochemotherapy. The patient underwent a
      mammography and ultrasonography. A CT scan of the abdomen showed metastatic
      disease. An excisional biopsy of the breast lump was performed; morphological
      features were identical to the original rectal cancer. Immunohistochemical
      results were negative for estrogen and progesterone receptors and gross cystic
      disease fluid protein-15, and intensity positive for cytokeratin 20 and
      carcinoembryonic antigen. The patient died after treatment with palliative
      chemotherapy. Metastatic disease from rectal carcinoma to the breast is a marker
      for disseminated metastatic spread with poor prognosis.

PMID- 22964816
TI  - Lack of association between SMOC2 polymorphism and age-related macular
      degeneration in Jordanian Arabs.

PMID- 22964817
TI  - Novel influenza A (H1N1) outbreak at a training institute in the Eastern Province
      of Saudi Arabia.

PMID- 22964818
TI  - Possible central nervous system vasculitis as an early presentation of Crohn's
      disease. A challenge in diagnosis and management.

PMID- 22964819
TI  - Depleted uranium. Is it potentially involved in the recent upsurge of
      malignancies in populations exposed to war dust?

PMID- 22964821
TI  - Patient online report of selective serotonin reuptake inhibitor-induced
      persistent postwithdrawal anxiety and mood disorders.

PMID- 22964822
TI  - Methylated DNA and total DNA in serum detected by one-step methylation-specific
      PCR is predictive of poor prognosis for breast cancer patients.
AB  - PURPOSE: We recently developed the one-step methylation-specific PCR (OS-MSP)
      assay which can detect methylated DNA (met-DNA) in serum with high sensitivity.
      To examine its prognostic value, we applied this new assay to the detection of
      met-DNA in serum of breast cancer patients. METHODS: Serum samples taken before
      surgery from 336 primary invasive breast cancer patients were subjected to the OS
      MSP assay for the promoter regions of GSTP1, RASSF1A, and RARbeta2. The assay
      outcome was considered positive when methylation was detected in at least one of
      these three genes. Total DNA content in serum was also determined. RESULTS: Of
      the 336 stage I/II patients, 33 (10%) were positive for met-DNA in serum and
      showed a significantly worse overall survival (OS) rate at 100 months (78 vs.
      95%; p = 0.002) than those with negative findings (n = 303). Patients with high
      total DNA in serum (n = 112) also showed a significantly worse OS rate at 100
      months (86 vs. 97%; p = 0.001) than those with low total DNA in serum (n = 224).
      Moreover, patients both positive for met-DNA and with high total DNA in serum (n
      = 18) showed a much worse OS rate at 100 months (65 vs. 94%; p < 0.001) than the
      others (n = 318). CONCLUSIONS: Met-DNA in serum detected with the OS-MSP assay
      constitutes a significant and independent prognostic factor, and its combination
      with total DNA in serum seems to be even more effective for prediction of
      prognosis for breast cancer patients.

PMID- 22964823
TI  - Genetic control of testis development.
AB  - Sex determination refers to the decision of the bipotential early gonads to
      develop as either testes or ovaries during embryogenesis. In mammals, a single
      genetic trigger involved in this pivotal decision has been identified on the Y
      chromosome: the testis-determining gene SRY/Sry. During embryogenesis, SRY
      triggers the differentiation of Sertoli cells from the supporting cell precursor
      lineage which would otherwise give granulosa cells in ovaries. Several testis
      specific events occur after SRY expression and the onset of Sertoli cell
      differentiation, notably Leydig cell differentiation, testis cord formation, and
      development of testis-specific vasculature. Although a number of genes involved
      in these events have been identified, how they relate to Sry action is poorly
      understood. Furthermore, even at the adult stage, some of these genes retain a
      key role in maintaining the testicular fate because conditional ablation of the
      genes leads to adult testis dysgenesis or transdifferentiation into an ovary.
      This sheds light on mammalian sex-reprogramming, despite the prevailing dogma
      that postnatal sex change does not occur in mammals. In this review, we summarize
      our current understanding of genetic pathways of testis determination and
      differentiation in mammals, particularly in the mouse and the human.

PMID- 22964824
TI  - Effects of a comprehensive nutritional program on pressure ulcer healing, length
      of hospital stay, and charges to patients.
AB  - The burden of pressure ulcers will intensify because of a rapidly increasing
      elderly population. The aim of this study was to examine the effects of a
      comprehensive, interdisciplinary nutritional protocol on pressure ulcer wound
      healing, length of hospital stays, and charges for pressure ulcer management. The
      pre/post quasi-experimental design study comprised of 100 patients (50 patients
      in each group) 60 years or older with pressure ulcer. Research questions were
      analyzed using descriptive statistics, frequencies, chi-square tests, and t
      tests. Study findings indicate that the intervention was effective in improving
      pressure ulcer wound healing, decreasing both hospital length of stay (LOS) for
      treatment of pressure ulcer and total hospital LOS, while showing no significant
      additional charges for treatment of pressure ulcers. The older adults are at the
      highest risk of developing pressure ulcers that result in prolonged
      hospitalization, high health care costs, increased mortality, and decreased
      quality of life.

PMID- 22964825
TI  - Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation
      recommendation statement.
AB  - DESCRIPTION: Reaffirmation of the 2004 U.S. Preventive Services Task Force
      (USPSTF) recommendation statement on screening for ovarian cancer. METHODS: A
      2008 review of the literature commissioned by the USPSTF revealed no new evidence
      about the benefits of screening for ovarian cancer but provided some new data
      about observed harms of screening. A bridge search to 2011 focused on evidence
      from randomized, controlled trials. POPULATION: This recommendation applies to
      asymptomatic women. It does not apply to women with known genetic mutations that
      increase their risk for ovarian cancer (for example, BRCA mutations).
      RECOMMENDATION: The USPSTF recommends against screening for ovarian cancer in
      women (D recommendation).

PMID- 22964826
TI  - Preliminary studies on the role and reactions of
      tetrakis(hydroxymethyl)phosphonium chloride in polyacrylamide gel dosimeters.
AB  - A major source of dosimetric inaccuracy in normoxic polymer gel dosimeters is
      local variations in the concentration of oxygen scavenger. Currently, a
      phosphorus compound, tetrakis(hydroxymethyl)phosphonium chloride (THPC), is the
      oxygen scavenger of choice in most polymer gel dosimetry studies. Reactions of
      THPC in a gel dosimeter are not limited to oxygen. It can possibly be consumed in
      reacting with gelling agent, water free-radicals and polymer radicals before,
      during and after irradiation, hence affecting the dose response of the dosimeter
      in several ways. These reactions are not fully known or understood. It is our
      hypothesis that THPC not only scavenges radical species but also modifies the
      morphology of the gelatin network and of the polymer, possibly by intervening in
      the polymerization of monomers. These hypotheses are investigated in an anoxic
      acrylamide-based gel dosimeter. Scanning electron microscopy results indicate
      gelatin pores decreasing from 70 to 40 um and a very different radiation-induced
      polymer structure in samples containing THPC; Fourier-transform Raman
      spectroscopy shows a two-fold reduction in the dose constants of monomer
      consumption; however, a significant change in the relative dose constants of
      monomer consumption as a function of dose could not be detected.

PMID- 22964828
TI  - Obesity in the elderly: an emerging health issue.

PMID- 22964827
TI  - Patterns of bone sarcomas as a second malignancy in relation to radiotherapy in
      adulthood and histologic type.
AB  - BACKGROUND: Radiotherapy decreases cancer mortality, but is associated with an
      increased incidence of second primary cancers, including osteosarcomas,
      especially after exposure in childhood. It remains uncertain whether radiation is
      related to other histologic types of bone sarcomas such as chondrosarcomas that
      are more common in adulthood. METHODS: Using data from 1973 to 2008 Surveillance
      Epidemiology and End Results registries, we evaluated long-term risk of bone
      cancer in 1,284,537 adult 5-year cancer survivors. We used standardized incidence
      ratios (SIR) to compare second bone sarcoma rates to the general population for
      each histologic type. We also used multivariate Poisson regression to estimate
      the relative risk (RR) associated with radiotherapy for the most common subtypes,
      osteosarcoma and chondrosarcoma. RESULTS: By the end of 2008, 159 second bone
      sarcomas were reported. Compared with the general population, the risk of
      developing any bone sarcoma was increased by 25% in patients with no history of
      radiotherapy [Observed (O) = 89, SIR = 1.25 (1.00-1.54)] and by 257% in patients
      with a history of radiotherapy [O = 70, SIR = 3.57 (2.78-4.50)]. For each
      histologic subtype, SIRs were higher among patients who had previously received
      radiotherapy than among those who had not. The RR for radiotherapy for
      osteosarcoma (n = 63) was 5.08 (3.05-8.59) and for chondrosarcoma (n = 69) was
      1.54 (0.88-2.59), and these risks were even greater for second sarcomas that
      arose in the radiotherapy field used to treat the first cancer [osteosarcoma, RR
      = 10.35 (4.96-23.66); chondrosarcoma RR = 8.21 (2.09-39.89)]. CONCLUSIONS: Our
      findings provide the first evidence of a likely association between radiation
      exposure and chondrosarcoma. IMPACT: These results further our understanding of
      radiotherapy-related cancer risks and will potentially direct practices in long
      term surveillance of cancer survivors.

PMID- 22964829
TI  - Vibrational heating in single-molecule switches: an energy-dependent density-of
      states approach.
AB  - In recent experiments, it has been shown that the switching rate of single
      molecule switches can show a rather complicated dependence on the applied bias
      voltage. Here, we discuss a minimal model which describes the switching process
      in terms of inelastic scattering processes of the tunneling electron by specific
      molecular vibrations. One important point is the introduction of an energy
      dependent electronic density of states around the Fermi energy. The influence of
      different model parameters on the switching rate is studied and we show that the
      inclusion of a variable density of states allows us to understand the non
      monotonic behavior of the switching rate observed in some experiments.

PMID- 22964830
TI  - In need of psychiatric help--leave a message after the beep.
AB  - BACKGROUND/AIM: Every day, a substantial proportion of the general population
      experiences the distressing and frightening signs of an upcoming psychiatric
      illness. The consequences can be enormous because severe psychiatric disorders
      typically cause the loss of the ability to work and often mean a long-term burden
      for both the patients and their families. Even though most developed countries
      have an exceptionally high density of general practitioners and psychiatrists in
      private practice, getting a mental health appointment and seeing a doctor is
      often very difficult for patients with acute psychiatric symptoms. This study
      aimed at quantifying the time delay involved in seeking medical attendance when
      psychiatric disorders begin to develop. METHODS: Two female actors with well
      proven experiences of realistically simulating the clinical presentation of
      depression and psychotic disorders made systematic phone calls to 106
      psychiatrists in private practice and 106 general practitioners (GPs) of the
      Zurich City area. The actors asked for an appointment at the doctor's earliest
      convenience due to acute psychiatric symptoms. We assessed (1) the number of
      phone calls it took to reach each doctor; (2) the time it took to book an
      appointment; (3) the time span between the first phone call and the earliest
      available appointment, and (4) the possibility of personal contact with a doctor
      prior to booking the appointment. RESULTS: A total of 383 phone calls were made
      by the two actors (227 to psychiatrists and 156 to GPs) which resulted in
      analyzable data from 102 psychiatrist and 106 GP practices. Two thirds (68%) of
      the phone calls to the psychiatrists in private practice were answered by voice
      mail, compared to 21% among the GPs. A personal contact was established with 56%
      of the psychiatrists and 95% of the GPs. On average, 7.3 phone calls were
      necessary to successfully book an appointment with a psychiatrist. Almost half of
      the psychiatrists (45.6%) were not accepting new patients so appointments were
      able to be booked in less than one third of cases (30.4%). The situation was
      significantly better with GPs (p < 0.002) but depended on clinical diagnosis (p <
      0.01). The waiting time to seeing a psychiatrist often far exceeded 7 days.
      CONCLUSIONS: A high density of psychiatrists in private practice does not
      necessarily improve the long and troublesome circumstances of obtaining a mental
      health appointment in acute psychiatric situations. Under these circumstances, a
      considerable proportion of patients might give up prior to seeing a doctor. This
      has important implications--many patients could miss the potential benefits from
      timely therapeutic interventions which can significantly modify both the acute
      and long-term course of the illness. The situation might be improved if
      psychiatrists and GPs joined forces in the form of group practices or networks as
      this would readily ensure (1) a rapid mental health triage by assessing and
      categorizing the urgency of mental health-related problems, and (2) timely
      therapeutic interventions whenever indicated.

PMID- 22964831
TI  - Configuration change of liquid crystal microdroplets coated with a novel
      polyacrylic acid block liquid crystalline polymer by protein adsorption.
AB  - 4-cyano-4'-pentylbiphenyl (5CB) microdroplets coated with PAA-b-LCP were
      successfully made via microfluidics. Their functionalized interfaces were
      examined for lysozyme and bovine serum albumin detection, which could be easily
      visualized with an optical microscope under crossed polarizers by the radial-to
      bipolar configurational change of the 5CB. This transition was strongly dependent
      on the electrostatic states of the proteins and PAA chains, which were controlled
      by the pH of the water. This study demonstrated a simple approach for the
      development of a liquid crystal-based sensor for label-free detection of
      proteins, which may have diverse applications in various biomedical fields.

PMID- 22964833
TI  - Extending our experimental reach: Toolbox reviews in Genetics.

PMID- 22964832
TI  - Investigation of c9orf72 in 4 neurodegenerative disorders.
AB  - OBJECTIVE To estimate the allele frequency of C9orf72 (G4C2) repeats in
      amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD),
      Alzheimer disease (AD), and Parkinson disease (PD). DESIGN The number of repeats
      was estimated by a 2-step genotyping strategy. For expansion carriers, we
      sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2
      haplotypes. SETTING Hospitals specializing in neurodegenerative disorders.
      SUBJECTS We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients
      with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD
      with the LRRK2 G2019S mutation. MAIN OUTCOME MEASURE The expansion frequency.
      RESULTS Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3%
      of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD
      but not in controls or patients with AD. It was significantly associated with
      family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS
      vs FTLD) was not associated with MAPT, APOE, or variability in the repeat
      flanking regions. Two patients with PD were carriers of 39 and 32 repeats with
      questionable pathological significance, since the 39-repeat allele does not
      segregate with PD. No expansion or intermediate alleles (20-29 repeats) were
      found among the G2019S carriers and AD cases with TAR DNA-binding protein 43
      positive inclusions. Surprisingly, the frequency of the 10-repeat allele was
      marginally increased in all 4 neurodegenerative diseases compared with controls,
      indicating the presence of an unknown risk variation in the C9orf72 locus.
      CONCLUSIONS The C9orf72 expansion is a common cause of ALS and FTLD, but not of
      AD or PD. Our study raises concern about a reliable cutoff for the pathological
      repeat number, which is important in the utility of genetic screening.

PMID- 22964834
TI  - Reginald Crundall Punnett: first Arthur Balfour Professor of Genetics, Cambridge,
      1912.
AB  - R. C. Punnett, the codiscoverer of linkage with W. Bateson in 1904, had the good
      fortune to be invited to be the first Arthur Balfour Professor of Genetics at
      Cambridge University, United Kingdom, in 1912 when Bateson, for whom it had been
      intended, declined to leave his new appointment as first Director of the John
      Innes Horticultural Institute. We here celebrate the centenary of the first
      professorship dedicated to genetics, outlining Punnett's career and his
      scientific contributions, with special reference to the discovery of "partial
      coupling" in the sweet pea (later "linkage") and to the diagram known as
      Punnett's square. His seeming reluctance as coauthor with Bateson to promote the
      reduplication hypothesis to explain the statistical evidence for linkage is
      stressed, as is his relationship with his successor as Arthur Balfour Professor,
      R. A. Fisher. The background to the establishment of the Professorship is also
      described.

PMID- 22964836
TI  - The selfish Segregation Distorter gene complex of Drosophila melanogaster.
AB  - Segregation Distorter (SD) is an autosomal meiotic drive gene complex found
      worldwide in natural populations of Drosophila melanogaster. During
      spermatogenesis, SD induces dysfunction of SD(+) spermatids so that SD/SD(+)
      males sire almost exclusively SD-bearing progeny rather than the expected 1:1
      Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own
      transmission at the expense of its bearers. Here we review the molecular and
      evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus
      gene complex involving two key loci--the driver, Segregation distorter (Sd), and
      the target of drive, Responder (Rsp)--and at least three upward modifiers of
      distortion. Molecular analyses show that Sd encodes a truncated duplication of
      the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA.
      The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells
      and, for reasons that remain unclear, appears to disrupt the histone-to-protamine
      transition in drive-sensitive spermatids bearing many Rsp satellite repeats but
      not drive-insensitive spermatids bearing few or no Rsp satellite repeats.
      Evolutionary analyses show that the Sd-RanGAP duplication arose recently within
      the D. melanogaster lineage, exploiting the preexisting and considerably older
      Rsp satellite locus. Once established, the SD haplotype collected enhancers of
      distortion and suppressors of recombination. Further dissection of the molecular
      genetic and cellular basis of SD-mediated distortion seems likely to provide
      insights into several important areas currently understudied, including the
      genetic control of spermatogenesis, the maintenance and evolution of satellite
      DNAs, the possible roles of small interfering RNAs in the germline, and the
      molecular population genetics of the interaction of genetic linkage and natural
      selection.

PMID- 22964835
TI  - Weak selection and protein evolution.
AB  - The "nearly neutral" theory of molecular evolution proposes that many features of
      genomes arise from the interaction of three weak evolutionary forces: mutation,
      genetic drift, and natural selection acting at its limit of efficacy. Such forces
      generally have little impact on allele frequencies within populations from
      generation to generation but can have substantial effects on long-term evolution.
      The evolutionary dynamics of weakly selected mutations are highly sensitive to
      population size, and near neutrality was initially proposed as an adjustment to
      the neutral theory to account for general patterns in available protein and DNA
      variation data. Here, we review the motivation for the nearly neutral theory,
      discuss the structure of the model and its predictions, and evaluate current
      empirical support for interactions among weak evolutionary forces in protein
      evolution. Near neutrality may be a prevalent mode of evolution across a range of
      functional categories of mutations and taxa. However, multiple evolutionary
      mechanisms (including adaptive evolution, linked selection, changes in fitness
      effect distributions, and weak selection) can often explain the same patterns of
      genome variation. Strong parameter sensitivity remains a limitation of the nearly
      neutral model, and we discuss concave fitness functions as a plausible underlying
      basis for weak selection.

PMID- 22964837
TI  - Genetic and genomic toolbox of the chordate Ciona intestinalis.
AB  - The experimental malleability and unique phylogenetic position of the sea squirt
      Ciona intestinalis as part of the sister group to the vertebrates have helped
      establish these marine chordates as model organisms for the study of
      developmental genetics and evolution. Here we summarize the tools, techniques,
      and resources available to the Ciona geneticist, citing examples of studies that
      employed such strategies in the elucidation of gene function in Ciona. Genetic
      screens, germline transgenesis, electroporation of plasmid DNA, and
      microinjection of morpholinos are all routinely employed, and in the near future
      we expect these to be complemented by targeted mutagenesis, homologous
      recombination, and RNAi. The genomic resources available will continue to support
      the design and interpretation of genetic experiments and allow for increasingly
      sophisticated approaches on a high-throughput, whole-genome scale.

PMID- 22964841
TI  - Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in
      rat cardiac tissues.
AB  - This study aim to evaluate the protective effect of silymarin on sodium fluoride
      induced oxidative stress in rat cardiac tissues. Animals were pretreated with
      silymarin at 20 and 10 mg/kg prior to sodium fluoride consumption (600 ppm
      through drinking water). Vitamin C at 10 mg/kg was used as standard antioxidant.
      There was a significant increase in thiobarbituric acid reactive substances level
      (59.36 +/- 2.19 nmol MDA eq/g tissue) along with a decrease in antioxidant
      enzymes activity (64.27 +/- 1.98 U/g tissue for superoxide dismutase activity and
      29.17 +/- 1.01 umol/min/mg protein for catalase activity) and reduced glutathione
      level (3.8 +/- 0.15 ug/mg protein) in the tissues homogenates of the sodium
      fluoride-intoxicated rats. Silymarin administration to animals before sodium
      fluoride consumption modified the levels of biochemical parameters.

PMID- 22964842
TI  - Relationship between muscle cocontraction and proficiency in whole-body
      sensorimotor synchronization: a comparison study of street dancers and
      nondancers.
AB  - In this study, we investigated muscle cocontraction during a street dance
      movement task to provide evidence that the level of muscle cocontraction is
      associated with degree of proficiency in whole-body sensorimotor synchronization
      movement. Skilled street dancers and nondancers were required to synchronize a
      knee-bending movement in a standing position to a metronome beat. The dancer
      group showed significantly smaller variability of temporal deviation (defined as
      the peak knee-flexion time minus beat onset time), and lower level of muscle
      cocontraction analyzed by electromyographic data of the agonist and antagonist
      muscles of the upper and lower leg than did the nondancer group. In addition,
      multiple regression analyses revealed that the group effect significantly
      predicted the level of muscle cocontraction. These results show that the level of
      muscle cocontraction in the lower limbs during whole-body sensorimotor
      synchronization movement is associated with the degree of proficiency of the
      movement.

PMID- 22964843
TI  - Comparison of quick diagnosis units and conventional hospitalization for the
      diagnosis of cancer in Spain: a descriptive cohort study.
AB  - OBJECTIVE: Quick diagnosis units (QDUs) in Spain provide patients with severe
      disease who would normally require hospitalization with the prompt and effective
      diagnosis they deserve. We compared the value and cost of a QDU and of
      conventional hospitalization in assessing patients with cancer. METHODS: In a
      descriptive cohort study, 169 patients with a final diagnosis of cancer were
      prospectively evaluated between November 2008 and April 2010. We also analyzed a
      retrospective cohort of 53 randomly selected patients with neoplasia hospitalized
      during this period. In addition to the variables time to diagnosis and length of
      stay, we compared the costs of both models using microcosting techniques.
      RESULTS: Colorectal cancer was the commonest cancer (26%). QDU patients were
      younger than hospitalized patients (68.3 vs. 74.7 years; p < 0.05), and there
      were also significant differences with respect to the source of referral (p <
      0.00001) and destination (p < 0.00001), but not regarding diagnosis (p > 0.34),
      reason for consultation (p > 0.26) and time to diagnosis/length of stay (Wilcoxon
      rank sum test, p > 0.05). The mean costs for hospitalization were EUR 4,059.37
      compared with EUR 601.84 in the QDU. CONCLUSION: For diagnostic purposes, cancer
      patients can be managed similarly in a QDU or in in-hospital settings, but the
      QDU model seems to incur fewer costs.

PMID- 22964844
TI  - Distal hyperintense vessels on FLAIR: a prognostic indicator of acute ischemic
      stroke.
AB  - BACKGROUND: Hyperintense vessels (HVs) on fluid-attenuated inversion recovery
      (FLAIR) are frequently observed in acute ischemic stroke (AIS). The presence of
      HVs represents altered blood flow from collaterals distal to arterial occlusion
      or stenosis. This study aimed to evaluate the prognostic value of HVs in AIS.
      METHODS: Fifty-four consecutive patients with acute middle cerebral artery
      occlusion were enrolled in the study. The location and extent of the HVs was
      determined by FLAIR. Clinical data were obtained and compared between patients
      with different grades of HVs. Additionally, the relationship between distal HVs
      and leptomeningeal collaterals (LMCs) was assessed using angiography. RESULTS:
      HVs were observed in 41 (75.9%) of the 54 patients enrolled. The initial NIHSS
      score was lower (p<0.001) and the infarction volume was smaller (p<0.001) in
      patients with distal HVs. Adjusting of other factors, regression analysis
      revealed that distal HVs are an independent predictor of a favorable outcome at
      90 days (p=0.006; OR 0.049; 95% CI 0.006-0.420). Furthermore, the presence of
      distal HVs was correlated with the presence of LMCs. CONCLUSION: Distal HVs may
      be a marker for LMCs and act as a predictor of a favorable clinical outcome for
      patients with AIS.

PMID- 22964845
TI  - Ultrafast exciton dynamics in Type II ZnTe-ZnSe colloidal quantum dots.
AB  - Ultrafast transient absorption spectroscopy is used to investigate the exciton
      dynamics of Type II ZnTe-ZnSe core-shell colloidal quantum dots. Surface-trapping
      is shown to occur within a few picosecond for hot electrons and with a few 10s of
      picoseconds for electrons cooled to the band-edge, and is the dominant process in
      the decay of the band-edge bleach for well-stirred samples pumped at moderate
      powers. The surface-trapped electrons produce a broad photo-induced absorption
      that spectrally overlaps with the band-edge, distorting and partially cancelling
      out the bleach feature. At high pump powers and for unstirred samples, these
      surface-trapped electrons can survive sufficiently long within the pumped volume
      to accumulate under repeated excitation of the sample, resulting in the formation
      of an additional exciton decay channel.

PMID- 22964839
TI  - Structure and function in the budding yeast nucleus.
AB  - Budding yeast, like other eukaryotes, carries its genetic information on
      chromosomes that are sequestered from other cellular constituents by a double
      membrane, which forms the nucleus. An elaborate molecular machinery forms large
      pores that span the double membrane and regulate the traffic of macromolecules
      into and out of the nucleus. In multicellular eukaryotes, an intermediate
      filament meshwork formed of lamin proteins bridges from pore to pore and helps
      the nucleus reform after mitosis. Yeast, however, lacks lamins, and the nuclear
      envelope is not disrupted during yeast mitosis. The mitotic spindle nucleates
      from the nucleoplasmic face of the spindle pole body, which is embedded in the
      nuclear envelope. Surprisingly, the kinetochores remain attached to short
      microtubules throughout interphase, influencing the position of centromeres in
      the interphase nucleus, and telomeres are found clustered in foci at the nuclear
      periphery. In addition to this chromosomal organization, the yeast nucleus is
      functionally compartmentalized to allow efficient gene expression, repression,
      RNA processing, genomic replication, and repair. The formation of functional
      subcompartments is achieved in the nucleus without intranuclear membranes and
      depends instead on sequence elements, protein-protein interactions, specific
      anchorage sites at the nuclear envelope or at pores, and long-range contacts
      between specific chromosomal loci, such as telomeres. Here we review the spatial
      organization of the budding yeast nucleus, the proteins involved in forming
      nuclear subcompartments, and evidence suggesting that the spatial organization of
      the nucleus is important for nuclear function.

PMID- 22964838
TI  - Nutritional control of growth and development in yeast.
AB  - Availability of key nutrients, such as sugars, amino acids, and nitrogen
      compounds, dictates the developmental programs and the growth rates of yeast
      cells. A number of overlapping signaling networks--those centered on Ras/protein
      kinase A, AMP-activated kinase, and target of rapamycin complex I, for instance-
      inform cells on nutrient availability and influence the cells' transcriptional,
      translational, posttranslational, and metabolic profiles as well as their
      developmental decisions. Here I review our current understanding of the
      structures of the networks responsible for assessing the quantity and quality of
      carbon and nitrogen sources. I review how these signaling pathways impinge on
      transcriptional, metabolic, and developmental programs to optimize survival of
      cells under different environmental conditions. I highlight the profound
      knowledge we have gained on the structure of these signaling networks but also
      emphasize the limits of our current understanding of the dynamics of these
      signaling networks. Moreover, the conservation of these pathways has allowed us
      to extrapolate our finding with yeast to address issues of lifespan, cancer
      metabolism, and growth control in more complex organisms.

PMID- 22964846
TI  - Morphine metabolism in human skin microsomes.
AB  - For patients with severe skin wounds, topically applied morphine is an option to
      induce efficient analgesia due to the presence of opioid receptors in the skin.
      However, for topical administration it is important to know whether the substance
      is biotransformed in the skin as this can eventually reduce the concentration of
      the active agent considerably. We use skin microsomes to elucidate the impact of
      skin metabolism on the activity of topically applied morphine. We are able to
      demonstrate that morphine is only glucuronidated in traces, indicating that the
      biotransformation in the skin can be neglected when morphine is applied
      topically. Hence, there is no need to take biotransformation into account when
      setting up the treatment regimen.

PMID- 22964848
TI  - Severe heart failure after bortezomib treatment in a patient with multiple
      myeloma: a case report and review of the literature.
AB  - BACKGROUND: Bortezomib is a novel, first-in-class peptide which reversibly
      inhibits the proteasome and is Food and Drug Administration approved for the
      treatment of multiple myeloma, non-Hodgkin lymphoma, Waldenstrom's
      macroglobulinemia, and systemic light chain amyloidosis, among others. CASE
      REPORT: Very few cases of bortezomib-induced cardiotoxicity have been reported in
      the literature, and most of them have been confounded by the previous use of
      anthracyclins. We reviewed the case of a 56-year-old woman with a medical history
      of well-controlled hypertension who was newly diagnosed with International
      Staging System stage I multiple myeloma. She presented with new symptoms of
      exertional dyspnea, paroxysmal nocturnal dyspnea, and orthopnea after a 4th cycle
      of a bortezomib/dexamethasone-based chemotherapy. Clinical examination was
      consistent with heart failure. 2-D echocardiogram showed an left ventricular
      ejection fraction of 25%, abnormal wall motion, severe eccentric mitral
      regurgitation, and moderate pericardial effusion. Coronary angiogram showed
      normal coronaries, and cardiac magnetic resonance did not show delayed gadolinium
      enhancement. CONCLUSION: We reviewed the possible mechanisms involved in
      cardiotoxicity caused by bortezomib, and the diagnostic methods and importance of
      early identification of this adverse event. Differential diagnoses such as
      cardiac amyloidosis and viral myocarditis are also discussed. To our knowledge,
      this is the first case where pericardial effusion and mitral regurgitation were
      described after bortezomib treatment.

PMID- 22964849
TI  - Stimulation of fat accumulation in hepatocytes by PGE2-dependent repression of
      hepatic lipolysis, beta-oxidation and VLDL-synthesis.
AB  - Hepatic steatosis is recognized as hepatic presentation of the metabolic
      syndrome. Hyperinsulinaemia, which shifts fatty acid oxidation to de novo
      lipogenesis and lipid storage in the liver, appears to be a principal elicitor
      particularly in the early stages of disease development. The impact of PGE2,
      which has previously been shown to attenuate insulin signaling and hence might
      reduce insulin-dependent lipid accumulation, on insulin-induced steatosis of
      hepatocytes was studied. The PGE2-generating capacity was enhanced in various
      obese mouse models by the induction of cyclooxygenase 2 and microsomal
      prostaglandin E-synthases (mPGES1, mPGES2). PGE2 attenuated the insulin-dependent
      induction of SREBP-1c and its target genes glucokinase and fatty acid synthase.
      Nevertheless, PGE2 enhanced incorporation of glucose into hepatic triglycerides
      synergistically with insulin. This was most likely due to a combination of a PGE2
      dependent repression of (1) the key lipolytic enzyme adipose triglyceride lipase,
      (2) carnitine-palmitoyltransferase 1, a key regulator of mitochondrial beta
      oxidation, and (3) microsomal transfer protein, as well as (4) apolipoprotein B,
      key components of the VLDL synthesis. Repression of PGC1alpha, a common upstream
      regulator of these genes, was identified as a possible cause. In support of this
      hypothesis, overexpression of PGC1alpha completely blunted the PGE2-dependent fat
      accumulation. PGE2 enhanced lipid accumulation synergistically with insulin,
      despite attenuating insulin signaling and might thus contribute to the
      development of hepatic steatosis. Induction of enzymes involved in PGE2 synthesis
      in in vivo models of obesity imply a potential role of prostanoids in the
      development of NAFLD and NASH.

PMID- 22964850
TI  - NHERF1 and CFTR restore tight junction organisation and function in cystic
      fibrosis airway epithelial cells: role of ezrin and the RhoA/ROCK pathway.
AB  - Tight junctions (TJs) restrict the transit of ions and molecules through the
      paracellular route and act as a barrier to regulate access of inflammatory cells
      into the airway lumen. The pathophysiology of cystic fibrosis (CF) lung disease
      is characterised by abnormal ion and fluid transport across the epithelium and
      polymorphonuclear (PMN) leukocyte-dominated inflammatory response. Na+/H+
      exchanger regulatory factor 1 (NHERF1) is a protein involved in PKA-dependent
      activation of CFTR by interacting with CFTR via its PDZ domains and with ezrin
      via its C-terminal domain. We have previously found that the NHERF1
      overexpression dependent rescue CFTR-dependent chloride secretion is due to the
      re-organisation of the actin cytoskeleton network induced by the formation of the
      multiprotein complex NHERF1-RhoA-ezrin-actin. In this context, we here studied
      whether NHERF1 and CFTR are involved in the organisation and function of TJs.
      F508del CFBE41o- monolayers presented nuclear localisation of zonula occludens
      (ZO-1) and occludin as well as disorganisation of claudin 1 and junction
      associated adhesion molecule 1 as compared with wild-type 16HBE14o- monolayers,
      paralleled by increased permeability to dextrans and PMN transmigration.
      Overexpression of either NHERF1 or CFTR in CFBE41o- cells rescued TJ proteins to
      their proper intercellular location and decreased permeability and PMN
      transmigration, while this effect was not achieved by overexpressing either
      NHERF1 deprived of ezrin-binding domain. Further, expression of a phospho-dead
      ezrin mutant, T567A, increased permeability in both 16HBE14o- cells and in a CFBE
      clone stably overexpressing NHERF1 (CFBE/sNHERF1), whereas a constitutively
      active form of ezrin, T567D, achieved the opposite effect in CFBE41o- cells. A
      dominant-negative form of RhoA (RhoA-N19) also disrupted ZO-1 localisation at the
      intercellular contacts dislodging it to the nucleus and increased permeability in
      CFBE/sNHERF1. The inhibitor Y27632 of Rho kinase (ROCK) increased permeability as
      well. Overall, these data suggest a significant role for the multiprotein complex
      CFTR-NHERF1-ezrin-actin in maintaining TJ organisation and barrier function, and
      suggest that the RhoA/ROCK pathway is involved.

PMID- 22964851
TI  - Heme oxygenase-1 promotes granuloma development and protects against
      dissemination of mycobacteria.
AB  - Non-tuberculous mycobacterial (NTM) infections occur in both immunocompromised
      and immunocompetent hosts and are an increasingly recognized cause of morbidity
      and mortality. The hallmark of pulmonary mycobacterial infections is the
      formation of granuloma in the lung. Our study focuses on the role of heme
      oxygenase-1 (HO-1), a cytoprotective enzyme, in the regulation of granuloma
      development and maturation following infection with Mycobacterium avium. We
      examined the role of HO-1 in regulating monocyte chemoattractant protein-1 (MCP
      1) and chemokine receptor 2 (CCR2), two molecules involved in monocyte-macrophage
      cell trafficking after infection. We showed that RAW 264.7 mouse monocytes
      exposed to M. avium expressed HO-1 and MCP-1. Inhibition of HO by zinc
      protoporphyrin-IX led to inhibition of MCP-1 and increased expression of CCR2,
      its cognate receptor. HO-1-/- mice did not develop organized granuloma in their
      lungs, had higher lung colony forming unit of M. avium when infected with
      intratracheal M. avium, and had loose collections of inflammatory cells in the
      lung parenchyma. Mycobacteria were found only inside defined granulomas but not
      outside granuloma in the lungs of HO-1+/+ mice. In HO-1-/- mice, mycobacteria
      were also found in the liver and spleen and showed increased mortality.
      Peripheral blood monocytes isolated from GFP+ mice and given intravenously to HO
      1+/+ mice localized into tight granulomas, while in HO-1-/- mice they remained
      diffusely scattered in areas of parenchymal inflammation. Higher MCP-1 levels
      were found in bronchoalveolar lavage fluid of M. avium infected HO-1(-/-) mice
      and CCR2 expression was higher in HO-1-/- alveolar macrophages when compared with
      HO-1+/+ mice. CCR2 expression localized to granuloma in HO-1+/+ mice but not in
      the HO-1-/- mice. These findings strongly suggest that HO-1 plays a protective
      role in the control of M. avium infection.

PMID- 22964852
TI  - Blood-brain barrier permeability is positively correlated with cerebral
      microvascular perfusion in the early fluid percussion-injured brain of the rat.
AB  - The blood-brain barrier (BBB) opening following traumatic brain injury (TBI)
      provides a chance for therapeutic agents to cross the barrier, yet the reduction
      of the cerebral microvascular perfusion after TBI may limit the intervention.
      Meanwhile, optimizing the cerebral capillary perfusion by the strategies such as
      fluid administration may cause brain edema due to the BBB opening post trauma. To
      guide the TBI therapy, we characterized the relationship between the changes in
      the cerebral capillary perfusion and BBB permeability after TBI. First, we
      observed the changes of the cerebral capillary perfusion by the intracardiac
      perfusion of Evans Blue and the BBB disruption with magnetic resonance imaging
      (MRI) in the rat subjected to lateral fluid percussion (FP) brain injury. The
      correlation between two variables was next evaluated with the correlation
      analysis. Since related to BBB breakdown, matrix metalloproteinase-9 (MMP-9)
      activity was finally detected by gelatin zymography. We found that the ratios of
      the perfused microvessel numbers in the lesioned cortices were significantly
      reduced at 0 and 1 h post trauma compared with that in the normal cortex, which
      then dramatically recovered at 4 and 24 h after injury, and that the BBB
      permeability was greatly augmented in the ipsilateral parts at 4, 12, and 24 h,
      and in the contralateral area at 24 h after injury compared with that in the
      uninjured brain. The correlation analysis showed that the BBB permeability
      increase was related to the restoration of the cerebral capillary perfusion over
      a 24-h period post trauma. Moreover, the gelatin zymography analysis indicated
      that the MMP-9 activity in the injured brain increased at 4 h and significantly
      elevated at 12 and 24 h as compared to that at 0 or 1 h after TBI. Our findings
      demonstrate that the 4 h post trauma is a critical turning point during the
      development of TBI, and, importantly, the correlation analysis may guide us how
      to treat TBI.

PMID- 22964853
TI  - Heat shock protein 90 inhibitor attenuates renal fibrosis through degradation of
      transforming growth factor-beta type II receptor.
AB  - The accumulation of extracellular matrix proteins in the interstitial area is the
      final common feature of chronic kidney diseases. Accumulating evidence suggests
      that transforming growth factor (TGF)-beta1 promotes the development of renal
      fibrosis. Heat shock protein (Hsp) 90 inhibitors have been shown to repress TGF
      beta1 signaling, but whether they inhibit renal fibrosis is unknown. The purpose
      of this study is to determine the therapeutic efficacy of Hsp90 inhibitor on
      renal fibrosis. In TGF-beta1-treated HK2 cells and unilateral ureteral
      obstruction (UUO) kidneys, we found that 17-allylamino-17-demethoxygeldanamycin
      (17AAG), an Hsp90 inhibitor, decreased the expression of alpha-smooth muscle
      actin, fibronectin, and collagen I and largely restored the expression of E
      cadherin. 17AAG inhibited TGF-beta1-mediated phosphorylation of Smad2, Akt,
      glycogen synthase kinase-3beta, and extracellular signal-regulated kinase in HK2
      cells. Inhibition of Hsp90 also blocked TGF-beta1-mediated induction of snail1.
      This 17AAG-induced reduction was completely restored by simultaneous treatment
      with proteasome inhibitor MG132. Furthermore, 17AAG blocked the interaction
      between Hsp90 and TGF-beta type II receptor (TbetaRII) and promoted
      ubiquitination of TbetaRII, leading to the decreased availability of TbetaRII.
      Smurf2-specific siRNA reversed the ability of 17AAG to inhibit TGF-beta1
      signaling. The effect of 17AAG on TbetaRII expression and renal fibrosis was
      confirmed in UUO kidneys. These findings suggest that Hsp90 inhibitor prevents
      the development of renal fibrosis via a mechanism dependent on Smurf2-mediated
      degradation of TbetaRII.

PMID- 22964854
TI  - The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell
      malignancies.
AB  - Diffuse large B-cell lymphoma (DLBCL) can present as de novo or can arise through
      the transformation of many indolent lymphomas, including follicular lymphoma
      (FL). The morphological differentiation between germinal center-DLBCL (GC-DLBCL)
      and high-grade (grade 3) FL could be challenging; the accurate sub-classification
      of large B-cell lymphomas is mandatory in order to select the most appropriate
      among the new-targeted therapies. Recent expression profiling studies reported
      microRNAs (miRNAs) (and miR-17-92 cluster, in particular) as useful tools in
      differentiating DLBCL and FL. However, these preliminary results are based on
      cell line-derived data or did not consider grade 3 FL cases. To investigate this
      point, 36 cases of GC-DLBCL and 18 cases of grade 3 non-transforming FL were
      considered. All diagnoses were based on the World Health Organization criteria
      and were confirmed by clinical, histological, and immunohistochemical data. Six
      members of the miR-17-92 cluster (ie, miR-18b, miR-19b, miR-20a, miR-92, miR-93,
      and miR-106a) and two control miRNAs (ie, miR-150 and miR-210) were quantified by
      quantitative reverse transcription-polymerase chain reaction. All the considered
      miR-17-92 cluster miRNAs were significantly overexpressed in GC-DLBCL, being miR
      20a and miR-106a the most dysregulated (P<0.001). Receiver operating
      characteristics (ROCs) analysis was used to find the optimal cut-off in
      distinguishing the two histotypes. The ROC estimated thresholds for miR-18b, miR
      19b, miR-20a, miR-92, and miR-106a displayed a sensitivity level higher than 0.80
      in achieving the GC-DLBCL diagnosis. The classification tree built on the six
      thresholds allowed the correct identification of 35/36 GC-DLBCL (97.2%).
      Profiling the miR-17-92 cluster is a promising investigative method for
      differentiating GC-DLBCL from high-grade FL. Subject to the validation of these
      findings in further larger studies; miR-17-92 cluster could represent a reliable,
      standardizable diagnostic tool for the sub-classification of large B-cell
      lymphoid neoplasm.

PMID- 22964855
TI  - Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and
      in vivo.
AB  - Studies related to the cancer stem cell hypothesis are challenging because of the
      imperfect tools to identify cell populations of interest and controversy on the
      usefulness of established cancer cell lines. We previously found CD133 to not be
      selective for a tumor-propagating or radioresistant population in a near-diploid,
      microsatellite-instable colorectal carcinoma (CRC) cell line. Because of
      discrepant literature data, we herein systematically analyzed the behavior of
      microsatellite-stable cell line subpopulations reflecting the more frequent
      carcinogenesis pathway in spontaneous CRC. CD133+ and CD133(-/low) populations
      were isolated by fluorescence-activated cell sorting and further processed. HT29
      and SW620 cells were studied in detail in monolayer and/or spheroid culture
      assays and upon subcutaneous injection in NMRI (nu/nu) mice using a limiting
      dilution approach. CD133(-/low) HT29 cells showed a significantly lower
      clonogenic survival and reduced spheroid formation capacity than their CD133+
      counterparts. However, the cell populations neither differed in growth kinetics
      and response to treatment in vitro nor in tumor formation capacity when injecting
      as low as 10 cells. CD133(-/low) HT29 cells rapidly re-expressed CD133 protein in
      vitro and in vivo as shown by flow cytometry and/or western blot analyses, and
      they also showed a particular survival benefit under tissue normoxic conditions.
      In contrast, CD133 protein in the CD133+ population was quite stable throughout
      culturing. The observation of CD133 re-expression and lack of difference in tumor
      take rate of subpopulations was confirmed in SW620 cells. Here, we found cell
      density to affect CD133 re-expression in the CD133(-)-sorted population. And even
      SW480 cells, classified as a CD133- cell line, presented some CD133 protein on
      their surface upon in vivo engraftment. We conclude that (i) CD133 protein
      expression shows high plasticity in CRC cell lines, and (ii) in vitro CD133
      status on the cell surface neither determines tumorigenic potential nor CD133
      profile in vivo.

PMID- 22964856
TI  - Determination of friction and pulling forces during a weighted sled pull.
AB  - Pulling or pushing weighted sleds has been included in various exercise programs.
      Coaches and researchers may wish to calculate work performed or estimate forces
      during these exercises, which would involve calculating coefficients of friction:
      static friction coefficient (MUs) and dynamic friction coefficient (MUd). The
      purpose of this study was to establish a reliable method for determining MUs,
      MUd, and pulling forces while pulling a weighted sled with different loads to
      quantify horizontal forces and work performed for training, assessment, and/or
      research. A nylon tether was attached to a sled-mounted force transducer, and a
      winch was used to pull the tethered sled at a constant velocity for 20 seconds.
      Three different loads were pulled: 44.8 kg (the unloaded weight of the sled),
      90.0 kg (44.8 kg sled with an additional load of 45.2 kg), and 136.2 kg (44.8 kg
      sled with an additional load of 91.4 kg). Each load was pulled 10 times using the
      winch for a total of 30 trials. The static friction coefficient (mean +/- SD) was
      0.47 +/- 0.01 (coefficient of variation [CV] = 2.2%), 0.42 +/- 0.01 (CV = 3.0%),
      and 0.39 +/- 0.01 (CV = 2.7%), whereas dynamic friction coefficient (mean +/- SD)
      was 0.35 +/- 0.01 (CV = 1.6%), 0.33 +/- 0.01 (CV = 3.7%), 0.31 +/- 0.00 (CV =
      1.0%) for 44.8, 90.0, and 136.2 kg, respectively (p < 0.01). When all trials and
      loads were combined, MUs = 0.43 +/- 0.04 and MUd = 0.33 +/- 0.02 with CV of 8.3
      and 5.6%, respectively. The friction coefficients determined in this study were
      very repeatable, as indicated by the low CV. Coaches, athletes, and researchers
      who wish to determine MUs and MUd for their own specific equipment and surfaces
      can use the methods described here to do so.

PMID- 22964857
TI  - Effect of age and activity level on lower extremity gait dynamics: an
      introductory study.
AB  - Elderly adults should perform exercises that maintain or improve balance to
      reduce risk of injury from falls. Bone fractures secondary to falls in the
      elderly, particularly sedentary females, continue to pose a major health and
      economic problem. A greater understanding of the processes that contribute to the
      propensity for falling may be obtained by considering changes in gait biodynamics
      with age and activity level. Therefore, the purpose of this study was to quantify
      the relationships between age/activity level and selected biodynamic parameters
      of the lower extremity during normal gait. Seventeen healthy women, 9 young and 8
      elderly, were divided into groups of 9 active and 8 sedentary subjects. Three
      dimensional (3D) video motion and force platform kinematic and kinetic data were
      collected from the hip, knee, and ankle of the right lower extremity as the
      subjects walked at self-selected speeds. Data were analyzed as functions of age
      and activity level by using a 2-way analysis of variance. As expected, our
      results show that the elderly group had significantly greater (p < 0.05)
      functional and mobility limitations in their lower extremity joints than did the
      younger group. Significant, age-related lower-limb gait alterations were
      manifested primarily at the ankle, whereas activity-related alterations were
      manifested most prominently at the hip. The knee showed the fewest changes
      accompanying age or activity level. Thus, age and activity level affect gait,
      which may have a role in the subsequent development of a predisposition to gait
      related imbalances and resultant falling and increased hip fracture risk.
      Strength and conditioning professionals may consider these factors related to age
      and activity level when individualizing exercise regimens for their older, or
      sedentary, clients. Prophylactic physical activities involving specific,
      controlled 3D body movements may help prevent abnormal lower-limb joint
      kinematics (and their hypothetically coupled, intrinsic postural control
      strategies), thereby reducing fall and fracture propensity.

PMID- 22964859
TI  - The effects of rest interval length manipulation of the first upper-body
      resistance exercise in sequence on acute performance of subsequent exercises in
      men and women.
AB  - The purpose of the present study was to investigate the effects of manipulating
      rest interval (RI) length of the first upper-body exercise in sequence on
      subsequent resistance exercise performance. Twenty-two men and women with at
      least 1 year of resistance training experience performed resistance exercise
      protocols on 3 occasions in random order. Each protocol consisted of performing 4
      barbell upper-body exercises in the same sequence (bench press, incline bench
      press, shoulder press, and bent-over row) for 3 sets of up to 10 repetitions with
      75% of 1 repetition maximum. Bench press RIs were 1, 2, or 3 minutes, whereas
      other exercises were performed with a standard 2-minute rest interval. The number
      of repetitions completed, average power, and velocity for each set of each
      exercise were recorded. Gender differences were observed during the bench press
      and incline press as women performed significantly (p <= 0.05) more repetitions
      than men during all RIs. The magnitude of decline in velocity and power over 3
      sets of the bench press and incline press was significantly higher in men than
      women. Manipulation of RI length during the bench press did not affect
      performance of the remaining exercises in men. However, significantly more
      repetitions were performed by women during the first set of the incline press
      using 3-minute rest interval than 1-minute rest interval. In men and women,
      performance of the incline press and shoulder press was compromised compared with
      baseline performances. Manipulation of RI length of the first exercise affected
      performance of only the first set of 1 subsequent exercise in women. All RIs led
      to comparable levels of fatigue in men, indicating that reductions in load are
      necessary for subsequent exercises performed in sequence that stress similar
      agonist muscle groups when 10 repetitions are desired.

PMID- 22964860
TI  - The use of Yo-Yo intermittent recovery level 1 and Andersen testing for fitness
      and maximal heart rate assessments of 6- to 10-year-old school children.
AB  - We evaluated a submaximal and maximal version of the Yo-Yo intermittent recovery
      level 1 children's (YYIR1C) test and the Andersen test for fitness and maximal
      heart rate assessments of children aged 6-10 years. Two repetitions of the YYIR1C
      and Andersen tests were carried out within 1 week by 6- to 7-year-olds and 8- to
      9-year-olds (grade 0, n = 17; grade 2, n = 16) and 6 weeks apart by 9- to 10-year
      olds (grade 3, n = 49). Grade 0-2 pupils also performed an incremental treadmill
      test (ITT). Grade 2 pupils had a better (p < 0.05) YYIR1C (84%; 994 +/- 399 m (+/
      SD) vs. 536 +/- 218 m) and Andersen test performance (10%; 1,050 +/- 71 m vs. 955
      +/- 56 m) than grade 0 pupils. For grade 0-2 pupils, YYIR1C, Andersen, and ITT
      peak heart rates were 205 +/- 11, 207 +/- 9, and 203 +/- 7 b.min(-1),
      respectively (Andersen > ITT, p < 0.05), and for grade 3 pupils, YYIR1C and
      Andersen peak heart rates were 208 +/- 9 and 204 +/- 9 b.min(-1), respectively
      (YYIR1C > Andersen, p < 0.05). Submaximal YYIR1C heart rate (HR) was inversely
      correlated (p < 0.05) with YYIR1C test performance (r = -0.54 to -0.67) and
      VO2peak (r = -0.42). The 6-week change in submaximal HR correlated with the
      change in YYIR1C test performance (r = -0.42 to -0.53, p < 0.05). In conclusion,
      YYIR1C and Andersen tests are simple and inexpensive intermittent field tests
      that can detect differences in fitness levels and determine maximal HR of 6- to
      10-year-old children. Additionally, submaximal YYIR1C testing can be used for
      frequent nonexhaustive fitness assessments.

PMID- 22964861
TI  - Reversible switching of single tin phthalocyanine molecules on the InAs(111)A
      surface.
AB  - Individual tin phthalocyanine (SnPc) molecules adsorbed on the InAs(111)A surface
      were studied by low-temperature scanning tunnelling microscopy (STM) at 5 K.
      Consistently with the nonplanar molecular structure, SnPc adopts two in-plane
      adsorption geometries with the centre Sn atom either above (SnPc(up)) or below
      (SnPc(down)) the molecular plane. Depending on the current and bias applied to
      the tunnel junction, the molecule can be reversibly switched between the two
      conformations, implying a controlled transfer of the Sn atom through the
      molecular plane. The SnPc(down) conformer is characterized by an enhanced surface
      bonding as compared to the SnPc(up) conformer. SnPc(up) molecules can be
      repositioned by the STM tip by means of lateral manipulation, whereas this is not
      feasible for SnPc(down) molecules. The reversible switching process thus enables
      one to either laterally move the molecule or anchor it to the semiconductor
      surface.

PMID- 22964862
TI  - Responding to pediatric providers' perceived barriers to adolescent weight
      management.
AB  - Primary care clinics are an ideal setting for early identification and possibly
      treatment of adolescent obesity. However, despite practice recommendations
      promoting preventive screening and monitoring of obesity, implementation has been
      modest. In this study, we interviewed providers to determine barriers to managing
      pediatric obesity, perceived skill in obesity interventions, and interest in
      additional training. The sensitivity of weight-related discussions and time were
      the 2 most significant barriers reported. We designed a brief training program,
      implemented it within a larger randomized controlled trial, and surveyed
      providers regarding its utility. The training was satisfactory to attendees and
      led to reported changes in practice patterns. Providers who received more
      complete training reported greater ease working with overweight teens and greater
      confidence that they could motivate teen patients to make healthy lifestyle
      changes compared with those who received less training. A fairly modest training
      intervention could improve patient care in the primary care setting.

PMID- 22964863
TI  - Automated tumour boundary delineation on (18)F-FDG PET images using active
      contour coupled with shifted-optimal thresholding method.
AB  - This study presents an automatic method to trace the boundary of the tumour in
      positron emission tomography (PET) images. It has been discovered that Otsu's
      threshold value is biased when the within-class variances between the object and
      the background are significantly different. To solve the problem, a double-stage
      threshold search that minimizes the energy between the first Otsu's threshold and
      the maximum intensity value is introduced. Such shifted-optimal thresholding is
      embedded into a region-based active contour so that both algorithms are performed
      consecutively. The efficiency of the method is validated using six sphere inserts
      (0.52-26.53 cc volume) of the IEC/2001 torso phantom. Both spheres and phantom
      were filled with (18)F solution with four source-to-background ratio (SBR)
      measurements of PET images. The results illustrate that the tumour volumes
      segmented by combined algorithm are of higher accuracy than the traditional
      active contour. The method had been clinically implemented in ten oesophageal
      cancer patients. The results are evaluated and compared with the manual tracing
      by an experienced radiation oncologist. The advantage of the algorithm is the
      reduced erroneous delineation that improves the precision and accuracy of PET
      tumour contouring. Moreover, the combined method is robust, independent of the
      SBR threshold-volume curves, and it does not require prior lesion size
      measurement.

PMID- 22964864
TI  - Perceived unmet needs and health-related quality of life of Chinese cancer
      survivors at 1 year after treatment.
AB  - BACKGROUND: Although advanced cancer treatments prolong survivors' lives, a
      significant proportion experienced poorer health-related quality of life (HRQoL)
      than general populations. Identifying their needs is essential to develop a
      health service delivery model to improve patient outcomes. OBJECTIVE: The
      objective of this study was to examine the perceived unmet needs and HRQoL of
      Chinese cancer survivors who completed treatment less than 1 year ago. METHODS:
      Three hundred seventy-six participants completed a self-report survey: the 34
      item Supportive Care Needs Survey, the supplementary module of access to
      healthcare and ancillary support services, and the Functional Assessment of
      Cancer Therapy: General. Descriptive statistics were used to examine the
      prevalence of unmet needs. Multivariable logistic regressions were conducted to
      identify participants' characteristics that were associated with unmet needs.
      Multiple linear regression was used to delineate which domains of unmet needs
      were significantly associated with HRQoL with adjustment for potential
      confounding factors. RESULTS: Healthcare information was the most common unmet
      needs among the survivors. Age, stage of cancer, and remission were significantly
      associated with 1 or more unmet need domains. Participants with unmet needs in
      physical, psychological, and patient care domains, on average, have poorer HRQoL.
      CONCLUSIONS: Chinese cancer survivors have various unmet needs that might have
      adverse effects on their HRQoL. Younger age, more advanced stages of cancer, and
      remission were factors contributing to further unmet needs. IMPLICATIONS FOR
      PRACTICE: The results provided useful information on the special needs of
      survivors that may affect their HRQoL, enabling clinicians to plan better how to
      allocate existing limited resources to those who most require them.

PMID- 22964865
TI  - 'Being a Part of Treatment': the meaning of self-monitoring for rural cancer
      patients.
AB  - BACKGROUND: The diagnosis and treatment of cancer entail managing vast amounts of
      information in order for patients to participate effectively in disease self
      management. Information management includes patients' responses to acquire,
      manage, and use external and internal information, such as through self
      monitoring practices. OBJECTIVE: The study objective was to examine the meaning
      of self-monitoring practices within the context of rural patients' responses to
      internal and external information. METHODS: An empirical phenomenological
      approach was used. Participants were adults 18 years or older, who were once
      diagnosed with cancer, who agreed to discuss health monitoring behavior in
      relation to their cancer experience, and who used services at a small, rural
      cancer center. Data were collected using semistructured interviews. RESULTS:
      Findings revealed a self-directed pursuit of self-monitoring that was shaped by 4
      factors, that is, cognitive, affective, interpersonal, and symptomatic.
      Quotations from participants illustrate these factors. "I'd ask the questions
      ..." represents the cognitive factor. "Are the horse stories about cancer
      treatments true?" represents the affective factor. The interpersonal factor is
      represented as "My nurse was there for me!" The symptomatic factor is represented
      as "Chemotherapy blocks out your memory." Informed by these factors,
      participants' self-monitoring practices fostered participants' sense of control
      and self-advocacy efforts. CONCLUSION: Nurses are in a strategic position to
      engage in supportive care practices through the facilitation of self-monitoring.
      IMPLICATIONS FOR PRACTICE: Assessment questions grounded in study findings are
      suggested for use by nurses to develop patient-centered education that
      facilitates self-monitoring practices.

PMID- 22964866
TI  - Factors influencing colorectal cancer screening in rural southern Taiwan.
AB  - BACKGROUND: Colorectal cancer (CRC) is the most common cancer in Taiwan.
      Colorectal cancer screening can prevent or detect cancer early, but the
      acceptance rate in rural southern Taiwan is unknown. OBJECTIVE: The purpose of
      this study was to explore the prevalence of CRC screening and related factors in
      rural south Taiwan. METHODS: Cross-sectional study was conducted. Sample
      population was recruited from 2 rural areas in southern Taiwan. A structured
      questionnaire was completed by 635 participants. The following outcomes were
      studied: sociodemographic characteristics, knowledge of CRC screening, acceptance
      of CRC screening, and the reasons for having or not having CRC screening.
      RESULTS: The results indicated that 4.7% of the respondents had undergone a fecal
      occult blood test, 3.1% had undergone a sigmoidoscopy, and 2.7% had undergone a
      colonoscopy. For overall CRC screening, knowledge that CRC was the most common
      form of cancer was significant (P < .01). Among participants who knew that CRC
      was the most common form of cancer, the odds of undergoing CRC screening were
      4.20-fold greater than among participants who did not know that CRC was the most
      common form of cancer (P < .01; confidence interval, 1.62-10.89). CONCLUSIONS:
      This study demonstrates that the acceptance of CRC screening among men remains
      higher than among women in rural southern Taiwan. Efforts to improve CRC
      screening in rural areas should focus on increasing community residents'
      knowledge about cancer incidence and prevention. IMPLICATIONS FOR PRACTICE:
      Colorectal cancer screening is a useful cancer prevention measure, and community
      health center nurses should assess and promote rural residents' acceptance for
      CRC screening.

PMID- 22964867
TI  - Young couples' experiences of breast cancer during hormone therapy: an
      interpretative phenomenological dyadic analysis.
AB  - BACKGROUND: Young women are confronted with the same consequences of cancer as
      older women are. In addition, they face problems specifically related to their
      age, such as their children's education and their family responsibilities,
      marital relationships, and career issues. OBJECTIVE: The objective was to
      identify the functioning profiles of young couples confronted with hormone
      therapy. METHODS: This study was both qualitative and dyadic. Interviews with 11
      couples revealed 5 themes. RESULTS: Initially, the partners reported increased
      intimacy and mutual support; however, during hormone therapy, a divergence
      developed between the patients and their partners. The partners wished for the
      couple to resume a normal life. The patients' loved ones, also helpful in the
      beginning, were tempted to promote this resumption of normalcy, with the risk
      that the patients' suffering would no longer be acknowledged. The risk of cancer
      recurrence appeared to immobilize the patients, who were unable to adopt a long
      term perspective. Finally, the experience of the disease led the participants to
      reorganize their priorities and promoted self-centering. CONCLUSIONS: Breast
      cancer affects both the patient and her loved ones. Future research should focus
      on qualitative extensions to other stages of cancer treatment and quantitative
      studies to measure the phenomena revealed in the current work. IMPLICATIONS FOR
      PRACTICE: Cancer and its treatment have impacts on the patient and her marriage;
      therefore, the focus for the clinical care should be on the couple rather than
      just the patient. Additionally, our findings suggest new areas of psychological
      dyadic counseling for cancer patients and their partners.

PMID- 22964869
TI  - A randomized trial of dyadic peer support intervention for newly diagnosed breast
      cancer patients in Korea.
AB  - BACKGROUND: At the time of diagnosis, patients with cancer are highly exposed to
      the risk of psychological morbidity. The effects of psychosocial intervention for
      newly diagnosed cancer patients have not been extensively studied. OBJECTIVE: The
      objective of this study was to test the effects of a dyadic peer support
      intervention on self-efficacy, anxiety, depression, and mental adjustment among
      newly diagnosed breast cancer patients in Korea. METHODS: This study used a
      randomized controlled trial design. One hundred twenty-nine patients were
      recruited within 1 month of diagnosis with breast cancer in the National Cancer
      Center in Korea. The study participants were randomly assigned to either
      experimental (n = 64) or control (n = 65) group. The experimental group underwent
      dyadic peer support intervention during the 6 weeks after surgery. The control
      group received the usual care. RESULTS: There was a significant difference in
      changes in self-efficacy for self-management of breast cancer between the
      experimental and control groups; however, no significant changes were observed in
      anxiety, depression, and mental adjustment between the 2 groups. CONCLUSIONS: A 6
      week dyadic peer support intervention was feasible and effective for increasing
      self-efficacy for self-management among newly diagnosed breast cancer patients in
      Korea. However, this intervention did not improve other psychological outcomes.
      IMPLICATIONS FOR PRACTICE: Oncology nurses are optimally positioned to promote
      adjustment in patients with cancer. Trained peer support partners, supervised by
      skilled nurses, may be useful in improving self-efficacy of patients newly
      diagnosed with breast cancer.

PMID- 22964868
TI  - Understanding the needs of women considering risk-reducing salpingo-oophorectomy.
AB  - BACKGROUND: Because of the significantly increased lifetime risk of ovarian
      cancer associated with inheritance of a germline mutation in the BRCA1/2 genes,
      women with a deleterious mutation are recommended to undergo risk-reducing
      salpingo-oophorectomy at age 35 years or once child-bearing is complete.
      Significant time is often spent by nurses trained in genetics providing
      counseling to improve the decision-making process. The decision to undergo
      surgery is complex and laden with several sources of uncertainty. OBJECTIVE: We
      conducted a qualitative study among female carriers of deleterious BRCA1/2
      mutations to address these uncertainties. METHODS: Twelve qualitative interviews
      were conducted with women who had received a positive BRCA1/2 test result to
      explore their understanding of ovarian cancer risk, prevention options, and
      resource needs. Qualitative content analysis was performed. RESULTS: Significant
      information gaps in level of risk, other factors associated with ovarian cancer,
      and details of prophylactic oophorectomy were identified. Personal experience
      with cancer colored the degree of risk perception associated with the inherited
      mutation. Fear of the adverse effects of surgical menopause, both physiological
      and psychosocial, was common. Women expressed interest in hearing from other
      women facing the same decision. CONCLUSIONS: Women facing the decision to undergo
      risk-reducing salpingo-oophorectomy have several information gaps and unmet needs
      despite comprehensive counseling. IMPLICATIONS FOR PRACTICE: Based on our
      findings, we make specific recommendations that will guide nursing practice and
      future research.

PMID- 22964870
TI  - Coping with breast cancer survivorship in Chinese women: the role of fatalism or
      fatalistic voluntarism.
AB  - BACKGROUND: The existing knowledge on fatalism in the field of cancer has arisen
      largely from the cancer prevention and screening literature. Little is known
      about the role of fatalism in cancer survivorship, particularly within Chinese
      population. OBJECTIVE: This study aimed to explore the role of fatalism in coping
      with breast cancer survivorship in Chinese women. METHODS: In-depth interviews
      were conducted on 29 participants selected from those who attended a local cancer
      self-help organization in China. Interview transcripts were transcribed and
      analyzed using qualitative content analysis. RESULTS: Although they actively
      engaged in emotional regulation and self-care management to cope with
      survivorship, participants believed in fatalism and accepted their inability to
      change the final outcome of cancer. Such contradictory behavioral and cognitive
      aspects of coping reported by participants highlighted the role of a complex
      belief system involving Ming in positively influencing the interpretation of
      fatalism and the actual coping efforts taken. CONCLUSIONS: Findings suggest that
      fatalism related to coping in the Chinese context combined 2 elements: fatalistic
      belief in and acceptance of the way things are as well as the exertion of
      personal efforts over the situation. As such, it seems more effectively depicted
      in terms of the emerging concept "fatalistic voluntarism." IMPLICATIONS FOR
      PRACTICE: When planning intervention for Chinese population, incorporating
      fatalistic voluntarism as a cognitive belief system in the process of adaptation
      to survivorship may be more culturally relevant for facilitating their coping
      behaviors.

PMID- 22964871
TI  - Pain in outpatients treated for breast cancer: prevalence, pharmacological
      treatment, and impact on quality of life.
AB  - BACKGROUND: Cancer pain is an unmitigated clinical phenomenon. Despite available
      guidelines, variability exists in treating cancer pain. OBJECTIVE: The objective
      of this study was to describe prevalence and severity of pain and the
      pharmacotherapy (opioid, nonopioid, adjuvant analgesics) in outpatients treated
      for breast cancer. Adequacy of pharmacological pain treatments, the predictors,
      and impact were also examined. METHODS: This descriptive study consisted of 114
      chemotherapy outpatients from urban and rural settings. Pain and quality of life
      were self-reported by patients; treatment-related information was obtained from
      medical records. Based on the World Health Organization analgesic ladder,
      adequacy of pharmacological pain management (acceptable or inadequate analgesia)
      was computed using the Pain Management Index; the most potent analgesic was
      prescribed relative to the patient's reported pain. RESULTS: Although patients
      were commonly treated with traditional analgesics, more than half (52.3%)
      received inadequate analgesia. Those who received inadequate analgesia reported
      more pain, greater pain interferences (P = .003), and more symptoms (P = .043).
      Those who received adjuvant analgesics reported more pain, greater interference
      (P = .018), more symptoms (P = .032), and lower functioning (P = .029).
      Nonadvanced disease stages and more comorbidities were strong predictors of
      inadequate analgesia. CONCLUSIONS: There is a lack of congruence between the
      strength of analgesia and the patient's pain level. The addition of adjuvant
      analgesics did not reduce pain severity or improve quality of life. IMPLICATIONS
      FOR PRACTICE: The risks and benefits of coadministration of traditional and
      adjuvant analgesics need to be determined. Other treatment modalities in
      conjunction with pharmacological treatment are needed, considering negative
      effects of adjuvant analgesics on pain and quality of life.

PMID- 22964872
TI  - A facile synthetic approach for copper iron sulfide nanocrystals with enhanced
      thermoelectric performance.
AB  - Chalcopyrite CuFeS(2) nanocrystals with a diameter of 6.4 nm were synthesized
      using a facile solution-phase method. Due to quantum confinement, the CuFeS(2)
      nanocrystals exhibit a maximum ZT value of 0.264 at 500 K, which is 77 times the
      value of bulk chalcopyrite.

PMID- 22964873
TI  - MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple
      Mitochondrial DNA Deletions.
AB  - OBJECTIVE To identify the cause of an adult-onset multisystemic disease with
      multiple deletions of mitochondrial DNA (mtDNA). DESIGN Case report. SETTING
      University hospitals. PATIENT A 65-year-old man with axonal sensorimotor
      peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise
      intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal
      dysmotility. RESULTS Skeletal muscle biopsy revealed ragged-red and cytochrome- c
      oxidase-deficient fibers, and Southern blot analysis showed multiple mtDNA
      deletions. No deletions were detected in fibroblasts, and the results of
      quantitative polymerase chain reaction showed that the amount of mtDNA was normal
      in both muscle and fibroblasts. Exome sequencing using a mitochondrial library
      revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and
      p.Leu143*), a novel cause of mtDNA multiple deletions. CONCLUSIONS In addition to
      causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause
      adult-onset multisystemic disease with multiple mtDNA deletions.

PMID- 22964874
TI  - The effect of voluntary training with family participation on early home
      discharge in patients with severe stroke at a convalescent rehabilitation ward.
AB  - BACKGROUND: The purpose of this study was to clarify the effects of voluntary
      training with family participation in addition to conventional rehabilitation for
      stroke patients. METHODS/DESIGN: The subjects were 49 first-time stroke patients
      with severe hemiplegia. They were divided into two groups: a family participation
      group, in which voluntary training was performed with family members (21
      patients), and a nonfamily participation group, in which voluntary training was
      performed with a physical therapist (28 patients). The groups were compared by
      background, cognitive and physical function, postadmission course, and outcome.
      RESULTS: There were shortened lengths of stay and higher rates of home discharge
      in family participation group, but no differences in functional recovery.
      CONCLUSIONS: Voluntary training with family participation was effective in
      shortening the length of hospital stay and in improving the rate of home
      discharge in a convalescent rehabilitation ward.

PMID- 22964875
TI  - Layer resolved evolution of the optical properties of alpha-sexithiophene thin
      films.
AB  - We report a combined reflectance difference spectroscopy and scanning tunneling
      microscopy study of ultrathin alpha-sexithiophene (6T) films deposited on the
      Cu(110)-(2*1)O surface. The correlation between the layer resolved crystalline
      structure and the corresponding optical spectra data reveals a highly sensitive
      dependence of the excitonic optical properties on the layer thickness and
      crystalline structure of the 6T film.

PMID- 22964876
TI  - Trauma-informed care for primary care: the lessons of war.

PMID- 22964877
TI  - Comparison of two inflammation-based prognostic scores in patients with
      unresectable advanced gastric cancer.
AB  - OBJECTIVES: The objective of this study was to compare the usefulness of two
      inflammation-based prognostic scores, neutrophil to lymphocyte ratio (NLR) and
      modified Glasgow Prognostic Score (mGPS), assessed at diagnosis in stage IV
      advanced gastric cancer (AGC). METHODS: We retrospectively reviewed the medical
      records of 104 patients with newly diagnosed metastatic AGC treated with
      palliative chemotherapy. RESULTS: In the univariate analysis, the following
      variables were associated with shorter overall survival (OS): poor or
      undifferentiated histology (p = 0.013), more than 1 metastasis (p = 0.004), the
      presence of lymph node metastasis (p = 0.003), the presence of bone metastasis (p
      = 0.019), a lower albumin level (p < 0.001), elevated C-reactive protein (p <
      0.001), a high absolute neutrophil count (p = 0.016), NLR >=3 (p < 0.001) and
      higher mGPS (p < 0.001 and p = 0.007, respectively). In the multivariate
      analysis, high NLR and mGPS were independent prognostic factors for shorter OS (p
      = 0.037, p < 0.001 and p = 0.010, respectively), along with lymph node metastasis
      (p = 0.005) and histological subtype (p = 0.048). CONCLUSION: This study suggests
      that the inflammatory markers, NLR and mGPS, are independent prognostic factors
      for OS in patients with unresectable AGC treated with palliative chemotherapy.

PMID- 22964878
TI  - Antimicrobial peptides and skin: a paradigm of translational medicine.
AB  - Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with
      broad-spectrum microbicidal activity against both bacteria and fungi. In mammals,
      AMPs form the first line of host defense against infections and generally play an
      important role as effector agents of the innate immune system. The AMP era was
      born more than 6 decades ago when the first cationic cyclic peptide antibiotics,
      namely polymyxins and tyrothricin, found their way into clinical use. Due to the
      good clinical experience in the treatment of, for example, infections of mucus
      membranes as well as the subsequent understanding of mode of action, AMPs are now
      considered for treatment of inflammatory skin diseases and for improving healing
      of infected wounds. Based on the preclinical findings, including
      pathobiochemistry and molecular medicine, targeted therapy strategies are
      developed and first results indicate that AMPs influence processes of diseased
      skin. Importantly, in contrast to other antibiotics, AMPs do not seem to
      propagate the development of antibiotic-resistant micro-organisms. Therefore,
      AMPs should be tested in clinical trials for their efficacy and tolerability in
      inflammatory skin diseases and chronic wounds. Apart from possible fields of
      application, these peptides appear suited as an example of the paradigm of
      translational medicine for skin diseases which is today seen as a 'two-way road' 
      from bench to bedside and backwards from bedside to bench.

PMID- 22964879
TI  - Trunk muscle reflex amplitudes increased in patients with subacute, recurrent LBP
      treated with a 10-week stabilization exercise program.
AB  - Altered trunk muscle reflexes have been observed in patients with low back pain
      (LBP). Altered reflexes may contribute to impaired postural control, and possibly
      recurrence of LBP. Specific stabilization exercise (SSE) programs have been shown
      to decrease the risk of LBP recurrence in a select group of patients with acute,
      first episode LBP. It is not known if trunk muscle reflex responses improve with
      resolution of subacute, recurrent LBP when treated with a SSE program. A
      perturbation test was used to compare trunk muscle reflexes in patients with
      subacute, recurrent LBP, before and after 10 weeks of a SSE program and a group
      of matched control subjects (CNTL). The LBP group pre therapy had delayed trunk
      muscle reflexes compared with the CNTL group. Post therapy reflex latencies
      remained delayed, but amplitudes increased. Increased reflex amplitudes could
      limit excessive movement of the spine when perturbed; potentially helping prevent
      recurrence.

PMID- 22964880
TI  - Measuring academic performance for healthcare researchers with the H index: which
      search tool should be used?
AB  - OBJECTIVES: To compare H index scores for healthcare researchers returned by
      Google Scholar, Web of Science and Scopus databases, and to assess whether a
      researcher's age, country of institutional affiliation and physician status
      influences calculations. SUBJECTS AND METHODS: One hundred and ninety-five Nobel
      laureates in Physiology and Medicine from 1901 to 2009 were considered. Year of
      first and last publications, total publications and citation counts, and the H
      index for each laureate were calculated from each database. Cronbach's alpha
      statistics was used to measure the reliability of H index scores between the
      databases. Laureate characteristic influence on the H index was analysed using
      linear regression. RESULTS: There was no concordance between the databases when
      considering the number of publications and citations count per laureate. The H
      index was the most reliably calculated bibliometric across the three databases
      (Cronbach's alpha = 0.900). All databases returned significantly higher H index
      scores for younger laureates (p < 0.0001). Google Scholar and Web of Science
      returned significantly higher H index for physician laureates (p = 0.025 and p =
      0.029, respectively). Country of institutional affiliation did not influence the
      H index in any database. CONCLUSION: The H index appeared to be the most
      consistently calculated bibliometric between the databases for Nobel laureates in
      Physiology and Medicine. Researcher-specific characteristics constituted an
      important component of objective research assessment. The findings of this study
      call to question the choice of current and future academic performance databases.

PMID- 22964881
TI  - Increased serum heat shock protein 27 antibody titers and prooxidant-antioxidant
      balance in patients with beta-thalassemia major.
AB  - OBJECTIVE: Determination of the serum heat shock protein 27 (Hsp27) antibody
      titers and prooxidant-antioxidant balance (PAB) in patients with thalassemia as
      markers of cell and oxidative stress, respectively. METHODS: Serum PAB and anti
      Hsp27 antibody titers were measured in 140 patients with thalassemia major and
      140 sex- and age-matched healthy volunteers. RESULTS: A significantly higher
      serum PAB value was observed in patients in comparison to controls. In the
      patient group, anti-Hsp27 antibody titers were significantly higher than for the
      control group (p < 0.001). We found a weak negative correlation between anti
      Hsp27 antibody concentrations and the PAB (p = 0.03), but these values were not
      correlated with serum superoxide dismutase activity in the thalassemic patients.
      CONCLUSIONS: Increased levels of serum PAB and Hsp27 antibodies may be involved
      in the pathological consequences of beta-thalassemia major and may contribute to
      the development of endothelial injury.

PMID- 22964882
TI  - The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate
      but does not significantly prolong survival in older patients with acute myeloid
      leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison.
AB  - The treatment of older patients with acute myeloid leukaemia, who are not
      considered suitable for conventional intensive therapy, is unsatisfactory. Low
      dose Ara-C(LDAC) has been established as superior to best supportive care, but
      only benefits the few patients who enter complete remission. Alternative or
      additional treatments are required to improve the situation. This randomised
      trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO),
      at a dose of 5 mg on day 1 of each course of LDAC, with the intention of
      improving the remission rate and consequently survival. Between June 2004 and
      June 2010, 495 patients entered the randomisation. The addition of GO
      significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32
      0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason
      for the induction benefit failing to improve OS was two-fold: survival of
      patients in the LDAC arm who did not enter remission and survival after relapse
      were both superior in the LDAC arm. Although the addition of GO to LDAC doubled
      the remission rate it did not improve overall survival. Maintaining remission in
      older patients remains elusive.

PMID- 22964883
TI  - Attention-related potentials allow for a highly accurate discrimination of mild
      cognitive impairment subtypes.
AB  - The three most frequent forms of mild cognitive impairment (MCI) are single
      domain amnestic MCI (sd-aMCI), single-domain dysexecutive MCI (sd-dMCI) and
      multiple-domain amnestic MCI (md-aMCI). Brain imaging differences among single
      domain subgroups of MCI were recently reported supporting the idea that
      electroencephalography (EEG) functional hallmarks can be used to differentiate
      these subgroups. We performed event-related potential (ERP) measures and
      independent component analysis in 18 sd-aMCI, 13 sd-dMCI and 35 md-aMCI cases
      during the successful performance of the Attentional Network Test. Sensitivity
      and specificity analyses of ERP for the discrimination of MCI subgroups were also
      made. In center-cue and spatial-cue warning stimuli, contingent negative
      variation (CNV) was elicited in all MCI subgroups. Two independent components
      (ICA1 and 2) were superimposed in the time range on the CNV. The ICA2 was
      strongly reduced in sd-dMCI compared to sd-aMCI and md-aMCI (4.3 vs. 7.5% and
      10.9% of the CNV component). The parietal P300 ERP latency increased
      significantly in sd-dMCI compared to md-aMCI and sd-aMCI for both congruent and
      incongruent conditions. This latency for incongruent targets allowed for a highly
      accurate separation of sd-dMCI from both sd-aMCI and md-aMCI with correct
      classification rates of 90 and 81%, respectively. This EEG parameter alone
      performed much better than neuropsychological testing in distinguishing sd-dMCI
      from md-aMCI. Our data reveal qualitative changes in the composition of the
      neural generators of CNV in sd-dMCI. In addition, they document an increased
      latency of the executive P300 component that may represent a highly accurate
      hallmark for the discrimination of this MCI subgroup in routine clinical
      settings.

PMID- 22964884
TI  - Tuning the interaction between carbon nanotubes and dipole switches: the
      influence of the change of the nanotube-spiropyran distance.
AB  - The non-covalent functionalization of carbon nanotubes with spiropyran molecules,
      serving as optically addressable dipole switches, is reported. Two kinds of
      pyrene-spiropyran-based dyads with spacers of different lengths resulting in
      different switch-tube distances were investigated. While both surfactants were
      able to form stable carbon nanotube suspensions, the different distances between
      the switch and the tube affected both of the components' optical properties. In
      the case of the shorter spacer, the nanotubes' luminescence as well as the
      merocyanine absorption band were red-shifted and furthermore, the rate of the
      merocyanine -> spiropyran thermal back isomerization was decreased.

PMID- 22964885
TI  - Minimally Invasive Lateral Lumbar Interbody Fusion: Clinical and Radiographic
      Outcome at a Minimum 2-year Follow-up.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the clinical and
      radiographic outcomes of patients undergoing minimally invasive lateral lumbar
      interbody fusion (LLIF) with a minimum 2-year follow-up. SUMMARY OF BACKGROUND
      DATA: Minimally invasive LLIF is performed through a lateral, retroperitoneal,
      transpsoas approach. This procedure is characterized by the use of a tubular
      retractor to minimize tissue damage and real-time neuromonitoring to ensure safe
      passage through the psoas muscle. To date, advantages of minimal invasive LLIF,
      compared with open procedures, has been limited to early postoperative outcomes
      and complications, with the longest mean follow-up duration of 22 months.
      METHODS: A total of 118 patients who underwent minimally invasive LLIF with a
      minimum of 2 years follow-up were included in this study. Clinical outcomes were
      determined by using Visual Analog Score for the degree of pain (trunk or lower
      extremity), and Oswestry Disability Index and Short Form-12 scoring methods for
      patient function. Radiographic evaluations included (i) disk height; (ii)
      segmental coronal angulation; (iii) segmental lordotic angulation; (iv) Cobb
      angle; (v) cage subsidence; and (vi) fusion status. Data were statistically
      tested using either paired Students t test or Wilcoxon matched-pair test.
      Significance level was set at P<0.05. RESULTS: We found that (i) the Visual
      Analog Score for pain, Oswestry Disability Index, and the physical components
      summary, but not the mental components summary of Short Form-12 improved
      significantly at the follow-up; (ii) disk height, coronal angulation, and
      lordotic angulation at each level and the Cobb angle were restored at the
      statistically significant extent; (iii) successful fusion was achieved in 209
      levels (88%); and (iv) transient thigh pain was the most frequent complication
      seen in 36% of the patients. CONCLUSIONS: Our results support the efficacy of
      minimally invasive LLIF in improvements of clinical and radiographic features.

PMID- 22964886
TI  - Oral antiretroviral chemoprophylaxis:  current status.
AB  - PURPOSE OF REVIEW: Preexposure prophylaxis (PrEP), in which HIV uninfected
      persons with ongoing HIV risk use oral antiretroviral medications as
      chemoprophylaxis against sexual HIV acquisition, is a promising new HIV
      prevention strategy. RECENT FINDINGS: During the past 2 years, proof-of-concept
      that PrEP protects against sexual HIV acquisition has been demonstrated in three
      clinical trials, conducted among MSM and heterosexual men and women. These trials
      used daily oral tenofovir disoproxil fumarate, alone or coformulated with
      emtricitabine. The degree of HIV protection in these trials was strongly related
      to the level of adherence to PrEP. Two additional clinical trials, both among
      heterosexual women, did not demonstrate HIV protection with PrEP, with low
      adherence to daily use of PrEP the leading hypothesis for lack of efficacy;
      adherence and biologic mechanisms for lack of efficacy in these trial populations
      are being evaluated. SUMMARY: Oral chemoprophylaxis, using tenofovir and
      combination emtricitabine-tenofovir, is effective for prevention of sexual HIV
      transmission. Next steps in the field include rigorous evaluation of uptake and
      adherence to PrEP in implementation settings.

PMID- 22964887
TI  - Adherence to preexposure chemoprophylaxis:  the behavioral bridge from efficacy
      to effectiveness.
AB  - PURPOSE OF REVIEW: Remarkable advances in the use of antiretroviral medication in
      the prevention of HIV acquisition are receiving well deserved widespread
      attention. The behavioral and social-cultural factors that contextualize use of
      study product or preexposure prophylaxis (PrEP) are comparatively poorly
      understood. Given that PrEP is a bio-behavioral intervention, optimizing the
      potential impact of PrEP on individual and public health requires a better
      understanding of the behavioral aspects of PrEP adherence. This review culls
      across available clinical trial findings to suggest a behavioral agenda for
      research and practice. RECENT FINDINGS: Product use differs dramatically both
      within and between recent PrEP trials; however, numerous issues with measuring
      use have emerged. Factors influencing use or adherence are not well identified
      and continue to focus on the individual and discrete correlates. Presently,
      execution and cyclical use of open-label PrEP is unknown but is under
      investigation in a number of demonstration and open-label projects. SUMMARY:
      Research to identify methods for assessing product and PrEP use, factors
      influencing individual and community-level PrEP uptake and use, development of
      comprehensive models of protection of sexual health via multiple strategies now
      available, and strategies to best support adherence to dosing and HIV-testing
      requirements are identified as critical in a behavioral research agenda.

PMID- 22964888
TI  - The clinical pharmacology of antiretrovirals for HIV prevention.
AB  - PURPOSE OF REVIEW: Pre-exposure prophylaxis (PrEP) clinical trial results using
      antiretrovirals can seem confusing, if not conflicting. We review recent
      antiretroviral pharmacokinetic studies to help explain PrEP trial results. RECENT
      FINDINGS: Pharmacokinetic studies indicate that topical dosing, compared with
      oral dosing, achieves far higher colon and vaginal tissue drug concentrations,
      and far lower drug concentrations in blood. After oral dosing, higher tenofovir
      diphosphate concentrations are found in colon tissue than cervico-vaginal tissue,
      but the reverse is the case for emtricitabine triphosphate, although it does not
      persist as long. Vaginal dosing achieves measurable tenofovir concentrations in
      the rectum and vice versa. Within and among oral PrEP trials, increased drug
      concentration is associated with increased HIV protection, with drug
      concentration differences best explained by adherence, rather than
      pharmacokinetics. The poor level of protection in topical studies is not
      consistent with concentration-response in oral studies indicating unknown
      variables in need of further investigation. SUMMARY: Sparse pharmacokinetic
      sampling in large trials combined with more intensive sampling in smaller
      pharmacokinetic-focused studies help explain trial outcome differences due
      largely to differences in adherence, tissue pharmacokinetics, and type of HIV
      exposure. Pharmacokinetic analysis can identify protective drug concentration
      targets, guide dose optimization, and inform future trials.

PMID- 22964889
TI  - Animal models of antiretroviral prophylaxis for HIV prevention.
AB  - PURPOSE OF REVIEW: Oral and topical pre-exposure prophylaxis (PrEP) with
      antiretroviral drugs are novel biomedical interventions recently found to prevent
      HIV transmission among high-risk populations. In this review, we outline lessons
      learned from animal studies and discuss next steps in preclinical PrEP research
      including the study of new PrEP modalities, pharmacologic correlates of
      protection, and biological factors that may modulate PrEP efficacy. RECENT
      FINDINGS: Studies using macaque or humanized mice models of mucosal simian
      immunodeficiency virus (SIV), HIV, or simian/human immunodeficiency virus (SHIV)
      transmission have provided efficacy data against rectal and vaginal infection. A
      multitude of oral and topical PrEP regimens including drugs such as tenofovir
      (TFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) were tested
      against either wild-type or drug-resistant viruses. These models have also helped
      define prophylactic windows of protection of nondaily dosing and are being used
      increasingly to study pharmacokinetic and pharmacodynamic relationships. SUMMARY:
      As human data from PrEP trials validate animal models or help fine tune them, it
      is expected that these models will play increasingly important roles in PrEP
      development as the field extends into new drug classes and combinations, episodic
      dosing, and novel long-acting drug formulations. By providing both efficacy and
      pharmacologic information these models can define correlates and mechanisms of
      protection, inform dose selection, and advance the most promising PrEP candidates
      and dosing modalities.

PMID- 22964891
TI  - Investigation of ultraviolet optical properties of semiconducting-enriched and
      metal-enriched single-walled carbon nanotube networks using spectroscopic
      ellipsometry.
AB  - The ultraviolet optical properties of semiconducting-enriched and metallic
      enriched single-walled carbon nanotube (semi-enriched and m-enriched SWCNT)
      networks were studied using spectroscopic ellipsometry. According to calculated
      energy loss function, the energy loss peak assigned to the maximum intensity of
      pi-plasmon energy was found to increase from 4.5 eV to 5.0 eV as SWCNT network
      composition was changed from m-SWCNT enriched to semi-SWCNT enriched. These
      results clearly demonstrate that the dielectric response in the 4-6 eV range is
      sensitive to changes in the surrounding dielectric environment depending on the
      semi-/m-SWCNT content. Therefore, the spectral shift of this energy loss is
      attributed to the enhanced electron confinement by the presence of the surface
      plasmon due to a small amount of m-SWCNT, which is an important phenomenon at the
      SWCNT network.

PMID- 22964890
TI  - Modeling of epigenome dynamics identifies transcription factors that mediate
      Polycomb targeting.
AB  - Although changes in chromatin are integral to transcriptional reprogramming
      during cellular differentiation, it is currently unclear how chromatin
      modifications are targeted to specific loci. To systematically identify
      transcription factors (TFs) that can direct chromatin changes during cell fate
      decisions, we model the relationship between genome-wide dynamics of chromatin
      marks and the local occurrence of computationally predicted TF binding sites. By
      applying this computational approach to a time course of Polycomb-mediated
      H3K27me3 marks during neuronal differentiation of murine stem cells, we identify
      several motifs that likely regulate the dynamics of this chromatin mark. Among
      these, the sites bound by REST and by the SNAIL family of TFs are predicted to
      transiently recruit H3K27me3 in neuronal progenitors. We validate these
      predictions experimentally and show that absence of REST indeed causes loss of
      H3K27me3 at target promoters in trans, specifically at the neuronal progenitor
      state. Moreover, using targeted transgenic insertion, we show that promoter
      fragments containing REST or SNAIL binding sites are sufficient to recruit
      H3K27me3 in cis, while deletion of these sites results in loss of H3K27me3. These
      findings illustrate that the occurrence of TF binding sites can determine
      chromatin dynamics. Local determination of Polycomb activity by REST and SNAIL
      motifs exemplifies such TF based regulation of chromatin. Furthermore, our
      results show that key TFs can be identified ab initio through computational
      modeling of epigenome data sets using a modeling approach that we make readily
      accessible.

PMID- 22964893
TI  - The resurgence of West Nile virus.

PMID- 22964894
TI  - Cerebral amyloid deposition and serotoninergic innervation in Parkinson disease.
AB  - BACKGROUND Prior studies suggest that serotoninergic neurotransmission reduces
      beta-amyloid (Abeta) production. OBJECTIVE To determine whether serotoninergic
      system degeneration in Parkinson disease promotes Abeta deposition, using in vivo
      positron emission tomographic probes of serotonin system integrity and Abeta
      deposition. DESIGN, SETTING, AND PATIENTS Cross-sectional study of 13 subjects
      with Parkinson disease from the movement disorders clinics at the University of
      Michigan Health System and Veterans Affairs Ann Arbor Healthcare System, with
      positron emission tomography using the serotonin transporter ligand carbon 11
      ([11C])-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile
      (DASB) and the Abeta ligand [11C]Pittsburgh compound B. RESULTS Inverse
      correlations were found between DASB and Pittsburgh compound B distribution
      volume ratios in the neocortex (rho = -0.577; P = .04) and striatum (rho = 
      0.780; P = .002). CONCLUSION Serotoninergic system degeneration in Parkinson
      disease may promote the development of cerebral amyloidopathy.

PMID- 22964895
TI  - Fractional anisotropy in three variants of primary progressive aphasia.
AB  - OBJECTIVE: Our aim was to report diffusion tensor imaging (DTI) patterns in three
      patients, each with a different primary progressive aphasia (PPA) variant.
      DESIGN: One agrammatic PPA, one semantic PPA, and one logopenic PPA subject
      underwent a magnetic resonance imaging examination including DTI sequences. The
      fractional anisotropy (FA) value was calculated in regions of interest (ROIs)
      involved in these three variants (perisylvian region, temporal pole, and
      parietotemporal junction) for each patient. Left-right FA ratios in each ROI were
      compared between PPA subjects and a group of three amnestic mild cognitive
      impairment patients with a cerebrospinal fluid biomarker profile of the Alzheimer
      type. RESULTS: The FA values were lower in the left hemisphere (p=0.03). The
      lowest FA values were observed in the left perisylvian region for the non
      fluent/agrammatic subtype PPA patient, in the left anterior temporal lobe for the
      semantic subtype PPA patient, and in the left parietotemporal junction for the
      logopenic patient (p=0.028). The left-right FA ratio in these specific ROIs for
      each PPA variant was significantly lower than in the amnestic mild cognitive
      impairment group (p=0.009). CONCLUSION: DTI patterns could be an effective new
      tool for diagnosing PPA and classifying the three variants.

PMID- 22964896
TI  - Oxazine-1 J-aggregates in polymer nanohybrids.
AB  - In a smart solution-processable luminescent poly(norbornene)/oxazine-1 (Ox1)
      intercalated fluoromica nanohybrid, the supramolecular organization of the Ox1
      dyes can be tuned at the nanoscale level and a deep red emission band switched on
      by inducing a phase segregation of aligned molecules within the fluoromica
      layered scaffold. By combining low-temperature photoluminescence and ultrafast
      pump-probe spectroscopy we prove that the nanoconstrained Ox1 molecules are
      organized in a J-type packing and we highlight the critical factor that controls
      such a supramolecular dye arrangement.

PMID- 22964897
TI  - Inspiratory muscle training in patients with heart failure: meta-analysis of
      randomized trials.
AB  - Patients with chronic heart failure (CHF) may have lower inspiratory muscle
      strength and endurance, which may contribute to exercise intolerance. Inspiratory
      muscle training (IMT) can have beneficial effects on these patients. Thus, the
      aim of this study was to systematically review the effects of IMT compared to
      control groups (placebo-IMT or another intervention) in patients with CHF. A
      search of databases (MEDLINE, Cochrane CENTRAL and PEDro) and references of
      published studies, from 1960 to 2011, was conducted. Randomized trials comparing
      IMT to control groups in the treatment of patients with CHF were included. The
      GRADE approach was used to determine the quality of evidence for each outcome. Of
      119 articles identified, 7 studies were included. IMT increased the distance
      walked in the six-minute walk test [69 m (95% CI: 7.21 to 130.79)] (very low
      evidence) and maximal static inspiratory pressure [23.36 cmH20 (95% CI: 11.71 to
      35.02)] (low evidence) compared to control groups. However, IMT provides a
      significant improvement in peak oxygen consumption only in the studies that
      performed IMT for 12 weeks against no inspiratory load in patients with
      inspiratory muscle weakness [3.02 ml/kg/min-1 (95% CI: 0.43 to 5.61)]. IMT
      improves functional capacity and inspiratory muscle strength thereby deserving
      consideration as an additional intervention in patients with CHF. Larger and
      better-designed studies, however, are needed to clarify the potential benefit of
      IMT in this patient population.

PMID- 22964898
TI  - Calculation of the ankle brachial index.

PMID- 22964899
TI  - Intracoronary ultrasound-guided stenting: is it really beneficial?

PMID- 22964900
TI  - Case 03/12: a 41-year-old female patient with hypertrophic cardiomyopathy and
      congestive heart failure.

PMID- 22964901
TI  - Use of therapeutic hypothermia in a patient with acute coronary heart disease.

PMID- 22964902
TI  - Giant aneurysm of saphenous vein bypass for right coronary after angioplasty.

PMID- 22964903
TI  - Outcome of trimodality-eligible esophagogastric cancer patients who declined
      surgery after preoperative chemoradiation.
AB  - BACKGROUND: For patients with localized esophageal cancer (EC) who can withstand
      surgery, the preferred therapy is chemoradiation followed by surgery
      (trimodality). However, after achieving a clinical complete response [clinCR;
      defined as both post-chemoradiation endoscopic biopsy showing no cancer and
      physiologic uptake by positron emission tomography (PET)], some patients decline
      surgery. The literature on the outcome of such patients is sparse. METHOD:
      Between 2002 and 2011, we identified 622 trimodality-eligible EC patients in our
      prospectively maintained databases. All patients had to be trimodality eligible
      and must have completed preoperative staging after chemoradiation that included
      repeat endoscopic biopsy and PET among other routine tests. RESULTS: Out of 622
      trimodality-eligible patients identified, 61 patients (9.8%) declined surgery.
      All 61 patients had a clinCR. The median age was 69 years (range 47-85). Males
      (85.2%) and Caucasians (88.5%) were dominant. Baseline stage was II (44.2%) or
      III (52.5%), and histology was adenocarcinoma (65.6%) or squamous cell carcinoma
      (29.5%). Forty-two patients are alive at a median follow-up of 50.9 months (95%
      CI 39.5-62.3). The 5-year overall and relapse-free survival rates were 58.1 +/-
      8.4 and 35.3 +/- 7.6%, respectively. Of 13 patients with local recurrence during
      surveillance, 12 had successful salvage resection. CONCLUSION: Although the
      outcome of 61 EC patients with clinCR who declined surgery appears reasonable, in
      the absence of a validated prediction/prognosis model, surgery must be encouraged
      for all trimodality-eligible patients.

PMID- 22964904
TI  - Immunohistochemical analysis of sensory nerve endings in ankle ligaments: a
      cadaver study.
AB  - BACKGROUND: The aim of this study was to analyze the pattern and types of sensory
      nerve endings in ankle ligaments using immunohistochemical techniques, in order
      to gain more insight into functional ankle stability. METHODS: One hundred forty
      ligaments from 10 cadaver feet were included: the calcaneofibular and
      anterior/posterior talofibular ligaments from the lateral complex; inferior
      extensor retinaculum complex, talocalcaneal oblique and canalis tarsi ligaments
      from the sinus tarsi; deltoid ligament with its individual portions from the
      medial complex, and anterior tibiofibular ligament (ATiFL) from the syndesmosis.
      Mechanoreceptors were classified according to Freeman and Wyke [Acta Anat (Basel)
      1967;68:321-333] after staining with hematoxylin-eosin, low-affinity neurotrophin
      receptor p75, protein gene product 9.5, and S-100 protein. RESULTS: Free nerve
      endings were the predominant sensory endings in all four complexes, with the
      greatest density in the lateral and medial complexes; followed by Ruffini
      endings, unclassifiable corpuscles, Pacini corpuscles, and Golgi-like endings.
      Ruffini endings were significantly more prevalent in the ATiFL than in the medial
      complex, and more common than Pacini corpuscles and Golgi-like endings in the
      lateral, medial, and sinus tarsi complexes. A greater number of blood vessels
      correlated with a greater number of free nerve endings. There was a negative
      correlation between the number of Ruffini endings, unclassifiable corpuscles, and
      age. CONCLUSIONS: Free nerve endings are the dominant mechanoreceptor type in the
      ankle ligaments, followed by Ruffini endings. The ligaments of the lateral and
      medial ankle complexes are more innervated than the sinus tarsi ligaments.

PMID- 22964905
TI  - Carbon nanotubes as substrates for molecular spiropyran-based switches.
AB  - We present a joint theory-experiment study investigating the excitonic absorption
      of spiropyran-functionalized carbon nanotubes. The functionalization is promising
      for engineering switches on a molecular level, since spiropyrans can be
      reversibly switched between two different conformations, inducing a
      distinguishable and measurable change of optical transition energies in the
      substrate nanotube. Here, we address the question of whether an optical read-out
      of such a molecular switch is possible. Combining density matrix and density
      functional theory, we first calculate the excitonic absorption of pristine and
      functionalized nanotubes. Depending on the switching state of the attached
      molecule, we observe a red-shift of transition energies by about 15 meV due to
      the coupling of excitons with the molecular dipole moment. Then we perform
      experiments measuring the absorption spectrum of functionalized carbon nanotubes
      for both conformations of the spiropyran molecule. We find good qualitative
      agreement between the theoretically predicted and experimentally measured red
      shift, confirming the possibility for an optical read-out of the nanotube-based
      molecular switch.

PMID- 22964906
TI  - Association between remnant-like particle cholesterol and gamma
      glutamyltransferase in dyslipidemic patients.
AB  - OBJECTIVE: To investigate the correlation between gamma-glutamyltransferase (GGT)
      and remnant-like particle cholesterol (RLP-C) in dyslipidemic patients. SUBJECTS
      AND METHODS: General cardiometabolic variables, plus serum GGT and RLP-C levels,
      were measured in 118 dyslipidemic patients (59 males, mean age 58 +/- 13 years).
      Correlation analyses of GGT with other variables, including RLP-C, were
      performed. RESULTS: The median levels (interquartile ranges) of RLP-C and GGT
      were 0.21 mmol/l (0.14-0.35) and 26 IU/l (17-39), respectively. A stepwise
      multiple regression analysis revealed an independent, significant and positive
      correlation between GGT and RLP-C (beta = 0.351, p < 0.001), followed by male
      gender and BMI. CONCLUSION: There was a significant positive association between
      GGT and RLP-C, thereby indicating that the association between GGT and
      cardiovascular disease may be partly due to the interaction with RLP-C in
      dyslipidemic patients. Further research is therefore warranted to confirm the
      observed relationship.

PMID- 22964907
TI  - Isolation of side population cells in B-cell non-Hodgkin's lymphomas.
AB  - BACKGROUND: Side population (SP) cells are characterized by the ability to
      exclude Hoechst 33342 dye due to high expression of the ATP-binding cassette
      transporter. This ability is associated with drug-resistant characteristics of
      cancer stem cells. METHODS: We analyzed SP cells from human B-cell non-Hodgkin's
      lymphoma cell lines and primary cells derived from patients and compared them
      with non-SP (NSP) cells. RESULTS: SP cells comprised a minor fraction of all
      cells ranging from 1.5 +/- 1.8 to 8.3 +/- 5.7% in cell lines and had higher ABCG2
      expression than NSP cells. SP cells had better cell viability, colony-forming
      ability and drug resistance than NSP cells. The SP cells also showed stem cell
      like characteristics, including elevated telomerase activity and higher
      expression of OCT4 and NANOG. A cDNA microarray demonstrated that SP cells had
      decreased expression of genes associated with apoptosis and cell death compared
      to NSP cells. CONCLUSIONS: The presence of SP cells might imply the possibility
      of lymphoma stem cells and be associated with a malignant potential of B-cell
      lymphoma.

PMID- 22964910
TI  - Frontotemporal dementia in a Brazilian kindred with the c9orf72 mutation.
AB  - OBJECTIVES: To describe the clinical features of a Brazilian kindred with C9orf72
      frontotemporal dementia-amyotrophic lateral sclerosis and compare them with other
      described families with C9orf72 and frontotemporal dementia-amyotrophic lateral
      sclerosis-causing mutations. DESIGN: Report of a kindred. SETTING: Dementia
      center at a university hospital. PATIENTS: One kindred encompassing 3
      generations. RESULTS: The presence of a hexanucleotide (GGGGCC) expansion in
      C9orf72 was confirmed by repeat-primed polymerase chain reaction and Southern
      blot. The observed phenotypes were behavioral variant frontotemporal dementia and
      amyotrophic lateral sclerosis with dementia, with significant variability in age
      at onset and duration of disease. Parkinsonian features with focal dystonia,
      visual hallucinations, and more posterior atrophy on neuroimaging than is typical
      for frontotemporal dementia were seen. CONCLUSIONS: Behavioral variant
      frontotemporal dementia due to C9orf72 expansion displays some phenotypic
      heterogeneity and may be associated with hallucinations, parkinsonism, focal
      dystonia, and posterior brain atrophy. Personality changes may precede the
      diagnosis of dementia by many years and may be a distinguishing feature of this
      mutation.

PMID- 22964911
TI  - C9orf72 hexanucleotide repeat expansions as the causative mutation for chromosome
      9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia.
AB  - OBJECTIVE: To further assess the presence of a large hexanucleotide repeat
      expansion in the first intron of the C9orf72 gene identified as the genetic cause
      of chromosome 9p21-linked amyotrophic lateral sclerosis and frontotemporal
      dementia (c9ALS/FTD) in 4 unrelated families with a conclusive linkage to
      c9ALS/FTD. DESIGN: A repeat-primed polymerase chain reaction assay. SETTING:
      Academic research. PARTICIPANTS: Affected and unaffected individuals from 4
      ALS/FTD families. MAIN OUTCOME MEASURE: The amplified C9orf72 repeat expansion.
      RESULTS: We show that the repeat is expanded in and segregated perfectly with the
      disease in these 4 pedigrees. CONCLUSION: Our findings further confirm the
      C9orf72 hexanucleotide repeat expansion as the causative mutation for c9ALS/FTD
      and strengthen the hypothesis that ALS and FTD belong to the same disease
      spectrum.

PMID- 22964912
TI  - A novel mutation in PNPLA2 leading to neutral lipid storage disease with
      myopathy.
AB  - BACKGROUND: Mutations in PNPLA2, a gene encoding adipose triglyceride lipase,
      lead to neutral lipid storage disease with myopathy. OBJECTIVE: To report the
      clinical and molecular features of a case of neutral lipid storage disease with
      myopathy resulting from a novel mutation in PNPLA2. DESIGN: Case report. SETTING:
      University hospital. PATIENT: A 65-year-old man with progressive muscle weakness
      and high serum creatine kinase levels. INTERVENTION: Direct sequencing of the
      PNPLA2 gene. RESULTS: Identification of a novel homozygous mutation in the
      patient's PNPLA2 gene confirmed the suspected diagnosis of neutral lipid storage
      disease with myopathy. CONCLUSION: Screening of the PNPLA2 gene should be
      considered for patients presenting with high levels of creatine kinase,
      progressive muscle weakness, and systemic lipid accumulation. The presence of
      Jordans anomaly can be a strong diagnostic clue.

PMID- 22964913
TI  - Two in one: report of a patient with spinocerebellar ataxia types 2 and 10.
AB  - OBJECTIVE: To report a rare case of the coexistence of 2 spinocerebellar ataxia
      (SCA) mutations in a single patient. DESIGN: Case report. SETTING: University
      hospital, Movement Disorders Center. PATIENT: A 54-year-old man of Mexican,
      American Indian, and French descent with an 11-year history of gait and limb
      ataxia. MAIN OUTCOME MEASURES: Findings of clinical examination, magnetic
      resonance imaging, and video electroencephalographic monitoring. RESULTS:
      Neurologic history revealed a gradually progressive gait and limb ataxia along
      with muscle cramps and sensory symptoms in his distal extremities; examination
      revealed executive dysfunction, dysarthria, ataxia, and sensory neuronopathy.
      Episodes of loss of awareness were reported, but electroencephalograms were
      negative. Brain imaging demonstrated severe cerebellar and brainstem atrophy.
      Genetic evaluation of the case revealed mutations in both the SCA2 and SCA10
      genes. CONCLUSION: Our patient has a unique combination of genetic mutations for
      2 different SCAs, types 2 and 10, which to our knowledge, has not been previously
      reported. His clinical phenotype is largely consistent with SCA2, but his
      possible seizures and Mexican heritage suggest influences of SCA10.

PMID- 22964914
TI  - Multiple fusiform intracranial aneurysms 14 years after atrial myxoma resection.

PMID- 22964915
TI  - Multiple septic brain emboli in infectious endocarditis.

PMID- 22964919
TI  - Primary progressive aphasia and transient global amnesia.

PMID- 22964920
TI  - Standard assumptions about the trial-by-trial distribution of averaged
      electromyography data could produce erroneous results.
AB  - The aim was to challenge the assumptions of standard statistical analyses of
      average surface electromyography (sEMG) data as a measurement of response
      magnitudes following the generation of a reflex. The ipsilateral tibial nerve was
      stimulated at three stimulation intensities and the response sEMG was measured in
      the contralateral soleus (cSOL) muscle. The magnitude of the cSOL response was
      measured at a set time window following ipsilateral tibial nerve stimulation. The
      averaged and trial-by-trial response magnitudes were assessed and compared. The
      analysis of the averaged and trial-by-trial response revealed significantly
      different results as the trial-by trial response magnitudes were log-normally
      distributed with between subject variance heterogeneity violating assumptions of
      standard statistical analyses. A statistical model has been suggested for the
      analysis of the responses. By ignoring trial-by-trial response variability and
      distribution, erroneous results may occur. This may change the interpretation of
      the results in some studies.

PMID- 22964921
TI  - Fluorescence bioimaging with conjugated polyelectrolytes.
AB  - This review summarizes the recent developments in fluorescent conjugated
      polyelectrolytes (CPEs) in bioimaging. The CPEs discussed include linear-,
      hyperbranched-, and polyhedral oligomeric silsesquioxanes (POSS)-based
      derivatives. Originating from their special optical properties, good
      photostability, low cytotoxicity, ease of bioconjugation and tuneable size, CPEs
      have shown wide applications in in vitro and in vivo protein and cell imaging,
      drug tracking and gene delivery. Moreover, some CPEs also possess antibacterial
      and anticancer characteristics as well as apoptosis imaging functions. Finally,
      this review discusses the future outlook of CPEs in bioimaging applications.

PMID- 22964923
TI  - Publication of the impact factor of the Brazilian Journal of Pulmonology: a
      milestone on a long and arduous journey.

PMID- 22964922
TI  - Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to
      serotonin-enhancing drugs: implications for drug side effects in humans.
AB  - A possible side effect of serotonin-enhancing drugs is the serotonin syndrome,
      which can be lethal. Here we examined possible hypersensitivity to two such
      drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical
      opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA)
      and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome
      behaviors, and these behavioral responses were highly exaggerated following 5-HTP
      or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B
      WT mice, baseline tissue serotonin levels were increased ~2.6-3.9-fold in MAOA/B
      KO mice. Following 5-HTP, serotonin levels were further increased ~4.5-6.2-fold
      in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated
      responses following serotonin-enhancing drugs that we previously observed in mice
      lacking the serotonin transporter (SERT). These findings provide a second genetic
      mouse model suggestive of possible human vulnerability to the serotonin syndrome
      in individuals with lesser-expressing MAO or SERT polymorphisms that confer
      serotonergic system changes. 

PMID- 22964924
TI  - Understanding mortality in bacteremic pneumococcal pneumonia.

PMID- 22964925
TI  - Impact of bacteremia in a cohort of patients with pneumococcal pneumonia.
AB  - OBJECTIVE: Bacteremia is the most common presentation of invasive disease in
      community-acquired pneumonia (CAP) due to Streptococcus pneumoniae. We
      investigated whether bacteremia in pneumococcal CAP worsens outcomes and whether
      it is related to pneumococcal vaccination (PV). METHODS: Secondary analysis of a
      cohort of patients with pneumococcal CAP confirmed by blood culture, sputum
      culture, or urinary antigen testing. Demographic, clinical, radiographic, and
      biochemical data were collected, as were Acute Physiology and Chronic Health
      Evaluation II (APACHE II) and pneumonia severity index (PSI) scores,
      comorbidities, and PV history. We drew comparisons between patients with
      bacteremic pneumococcal CAP (BPP) and those with non-bacteremic pneumococcal CAP
      (NBPP). RESULTS: Forty-seven patients had BPP, and 71 had NBPP (confirmed by
      sputum culture in 45 and by urinary antigen testing in 26); 107 had some
      indication for PV. None of the BPP patients had received PV, compared with 9 of
      the NBPP patients (p = 0.043). Among the BPP patients, the mean age was higher
      (76.4 +/- 11.5 vs. 67.5 +/- 20.9 years), as were APACHE II and PSI scores (16.4
      +/- 4.6 vs. 14.1 +/- 6.5 and 129.5 +/- 36 vs. 105.2 +/- 45, respectively), as
      well as the rate of ICU admission for cardiopathy or chronic renal failure (42.5%
      vs. 22.5%), whereas hematocrit and plasma sodium levels were lower (35.7 +/- 5.8
      vs. 38.6 +/- 6.7% and 133.9 +/- 6.0 vs. 137.1 +/- 5.5 mEq/L, respectively),
      although mortality was similar (29.8% vs. 28.2%). CONCLUSIONS: In this population
      at high risk for CAP due to S. pneumoniae, the PV rate was extremely low (8.4%).
      Although BPP patients were more severely ill, mortality was similar between the
      two groups. Because PV reduces the incidence of BPP, the vaccination rate in at
      risk populations should be increased.

PMID- 22964926
TI  - Evaluation of the efficacy and safety of a fixed-dose, single-capsule budesonide
      formoterol combination in uncontrolled asthma: a randomized, double-blind,
      multicenter, controlled clinical trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a fixed-dose, single-capsule
      budesonide-formoterol combination, in comparison with budesonide alone, in
      patients with uncontrolled asthma. METHODS: This was a randomized, double-blind,
      multicenter, phase III, parallel clinical trial, comparing the short-term
      efficacy and safety of the combination of budesonide (400 ug) and formoterol (12
      ug), with those of budesonide alone (400 ug), both delivered via a dry powder
      inhaler, in 181 patients with uncontrolled asthma. The age of the patients ranged
      from 18 to 77 years. After a run-in period of 4 weeks, during which all of the
      patients received budesonide twice a day, they were randomized into one of the
      treatment groups. for 12 weeks. The treatment consisted of the administration of
      the medications twice a day for 12 weeks. The primary outcome measures were FEV1,
      FVC, and morning PEF. We performed an intention-to-treat analysis of the data.
      RESULTS: In comparison with the budesonide-only group patients, those treated
      with the budesonide-formoterol combination showed a significant improvement in
      FEV1 (0.12 L vs. 0.02 L; p = 0.0129) and morning PEF (30.2 L/min vs. 6.3 L/min; p
      = 0.0004). These effects were accompanied by good tolerability and safety, as
      demonstrated by the low frequency of adverse events, only minor adverse events
      having occurred. CONCLUSIONS: The single-capsule combination of budesonide and
      formoterol appears to be efficacious and safe. Our results indicate that this
      formulation is a valid therapeutic option for obtaining and maintaining asthma
      control. (ClinicalTrials.gov Identifier: NCT01676987
      [http://www.clinicaltrials.gov/]).

PMID- 22964927
TI  - Children and adolescents with mild intermittent or mild persistent asthma:
      aerobic capacity between attacks.
AB  - OBJECTIVE: To assess children and adolescents diagnosed with mild intermittent or
      mild persistent asthma, in terms of their aerobic capacity between attacks.
      METHODS: We included 33 children and adolescents recently diagnosed with asthma
      (mild intermittent or mild persistent) and 36 healthy children and adolescents.
      Those with asthma were evaluated between attacks. All participants underwent
      clinical evaluation; assessment of baseline physical activity level; pre- and
      post-bronchodilator spirometry; and a maximal exercise test, including
      determination of maximal voluntary ventilation, maximal oxygen uptake,
      respiratory quotient, maximal minute ventilation, ventilatory equivalent,
      ventilatory reserve, maximal HR, SpO2, and serum lactate. RESULTS: No significant
      differences were found among the groups (intermittent asthma, persistent asthma,
      and control) regarding anthropometric or spirometric variables. There were no
      significant differences among the groups regarding the variables studied during
      the maximal exercise test. CONCLUSIONS: A diagnosis of mild
      intermittent/persistent asthma has no effect on the aerobic capacity of children
      and adolescents between asthma attacks.

PMID- 22964928
TI  - Fiberoptic bronchoscopy findings in patients diagnosed with lung cancer.
AB  - OBJECTIVE: To compile fiberoptic bronchoscopy findings in patients diagnosed with
      lung cancer and to correlate those with histopathological findings. METHODS: This
      was a retrospective study involving 212 patients with a confirmed diagnosis of
      lung cancer by cytological evaluation of BAL specimens or by histopathological
      evaluation of endobronchial or transbronchial biopsy specimens. The data were
      collected at the Respiratory Endoscopy Sector of Hospital Sao Salvador, located
      in the city of Goiania, Brazil, between 2005 and 2010. The endoscopic findings
      were classified as endoscopically visible tumor, endoscopically invisible tumor,
      mucosal injury, as well as being classified by the presence/type of secretion.
      The visible tumors were also classified according to their location in the
      tracheobronchial tree. RESULTS: Endobronchial mass (64%) and mucosal infiltration
      (35%) were the main endoscopic findings. The histological type was determined in
      199 cases, the most prevalent types being squamous carcinoma, in 78 (39%),
      adenocarcinoma, in 42 (21%) small cell carcinoma, in 24 (12%), and large cell
      carcinoma, in 2 (1%). More than 45% of the visible tumors were at the upper
      bronchi. Squamous carcinoma (n = 78) was most commonly visualized as an
      endobronchial mass (in 74%), mucosal infiltration (in 36%), luminal narrowing (in
      10%), or external compression (in 6%). CONCLUSIONS: Our results show that the
      endobronchial mass is the most common bronchoscopic finding that is suggestive of
      malignancy. Proportionally, mucosal infiltration is the most common finding in
      small cell carcinoma. In adenocarcinoma, luminal narrowing, external compression,
      mucosal injury, and endobronchial secretion prevail.

PMID- 22964929
TI  - Comparison of two experimental models of pulmonary hypertension.
AB  - OBJECTIVE: To compare two models of pulmonary hypertension (monocrotaline and
      monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of
      pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival.
      METHODS: We used 80 Sprague-Dawley rats in two study protocols: structural
      analysis; and survival analysis. The rats were divided into four groups: control;
      monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In
      the structural analysis protocol, 40 rats (10/group) were catheterized for the
      determination of hemodynamic variables, followed by euthanasia for the removal of
      heart and lung tissue. The right ventricle (RV) was dissected from the
      interventricular septum (IS), and the ratio between RV weight and the weight of
      the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV
      hypertrophy. In lung tissues, we performed histological analyses, as well as
      using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40
      animals (10/group) were followed for 45 days. RESULTS: The M and M+P rats
      developed pulmonary hypertension, whereas the control and P rats did not. The
      RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as
      being significantly higher in M and M+P rats than in control and P rats. There
      were no significant differences between the M and M+P rats regarding the area of
      the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival.
      CONCLUSIONS: On the basis of our results, we cannot conclude that the
      monocrotaline+pneumonectomy model is superior to the monocrotaline model.

PMID- 22964930
TI  - An experimental rat model of ex vivo lung perfusion for the assessment of lungs
      regarding histopathological findings and apoptosis: low-potassium dextran vs.
      histidine-tryptophan-ketoglutarate.
AB  - OBJECTIVE: To compare histopathological findings and the degree of apoptosis
      among rat lungs preserved with low-potassium dextran (LPD) solution, histidine
      tryptophan-ketoglutarate (HTK) solution, or normal saline (NS) at two ischemia
      periods (6 h and 12 h) using an experimental rat model of ex vivo lung perfusion.
      METHODS: Sixty Wistar rats were anesthetized, randomized, and submitted to
      antegrade perfusion via pulmonary artery with one of the preservation solutions.
      Following en bloc extraction, the heart-lung blocks were preserved for 6 h or 12
      h at 4 oC and then reperfused with homologous blood for 60 min in an ex vivo lung
      perfusion system. At the end of the reperfusion, fragments of the middle lobe
      were extracted and processed for histopathological examination. The parameters
      evaluated were congestion, alveolar edema, alveolar hemorrhage, inflammatory
      infiltrate, and interstitial infiltrate. The degree of apoptosis was assessed
      using the TdT-mediated dUTP nick end labeling method. RESULTS: The
      histopathological examination showed that all of the lungs preserved with NS
      presented alveolar edema after 12 h of ischemia. There were no statistically
      significant differences among the groups in terms of the degree of apoptosis.
      CONCLUSIONS: In this study, the histopathological and apoptosis findings were
      similar with the use of either LPD or HTK solutions, whereas the occurrence of
      edema was significantly more common with the use of NS.

PMID- 22964931
TI  - Anthropometric and dietary intake indicators as predictors of pulmonary function
      in cystic fibrosis patients.
AB  - OBJECTIVE: To evaluate whether anthropometric and dietary intake indicators are
      predictors of pulmonary function in cystic fibrosis (CF) patients. METHODS: This
      was a cross-sectional study involving 69 patients (age range, 5.4-16.5 years)
      diagnosed with CF under follow-up at the Hospital de Clinicas de Porto Alegre,
      located in the city of Porto Alegre, Brazil. Anthropometric assessment was based
      on body mass index (BMI), mid-arm muscle circumference (MAMC), and triceps
      skinfold thickness (TST). Dietary intake was assessed by using recall data, which
      were compared with the recommended dietary allowances. Pulmonary function was
      assessed by ventilatory capacity, expressed as FEV(1). Prevalence ratios for the
      outcome studied (FEV(1) < 80% of predicted) were calculated by indicator.
      RESULTS: In patients with MAMC and TST below the 25th percentile, the prevalence
      of FEV(1) < 80% of predicted was significantly higher than in those with higher
      MAMC and TST (p < 0.001 and p = 0.011, respectively). In comparison with other
      patients, those with a BMI below the 50th percentile showed a 4.43 times higher
      prevalence of FEV(1) < 80% of predicted (95% CI: 1.58-12.41), and that prevalence
      was 2.54 times higher in those colonized with methicillin-resistant
      Staphylococcus aureus (MRSA) than in those not so colonized (95% CI: 1.43-4.53).
      The association between dietary intake and the prevalence of FEV1 < 80% of
      predicted was of only borderline significance (95% CI: 0.95-3.45). CONCLUSIONS:
      Not being colonized with MRSA and having a BMI above the 50th percentile appear
      to preserve pulmonary function in CF patients.

PMID- 22964932
TI  - Manual hyperinflation combined with expiratory rib cage compression for reduction
      of length of ICU stay in critically ill patients on mechanical ventilation.
AB  - OBJECTIVE: Although manual hyperinflation (MH) is widely used for pulmonary
      secretion clearance, there is no evidence to support its routine use in clinical
      practice. Our objective was to evaluate the effect that MH combined with
      expiratory rib cage compression (ERCC) has on the length of ICU stay and duration
      of mechanical ventilation (MV). METHODS: This was a prospective randomized
      controlled clinical trial involving ICU patients on MV at a tertiary care
      teaching hospital between January of 2004 and January of 2005. Among the 49
      patients who met the study criteria, 24 and 25 were randomly assigned to the
      respiratory physiotherapy (RP) and control groups, respectively. Of those same
      patients, 6 and 8, respectively, were later withdrawn from the study. During the
      5-day observation period, the RP patients received MH combined with ERCC, whereas
      the control patients received standard nursing care. RESULTS: The two groups were
      similar in terms of the baseline characteristics. The intervention had a positive
      effect on the duration of MV, as well as on the ICU discharge rate and Murray
      score. There were significant differences between the control and RP groups
      regarding the weaning success rate on days 2 (0.0% vs. 37.5%), 3 (0.0% vs.
      37.5%), 4 (5.3% vs. 37.5%), and 5 (15.9% vs. 37.5%), as well as regarding the ICU
      discharge rate on days 3 (0% vs. 25%), 4 (0% vs. 31%), and 5 (0% vs. 31%). In the
      RP group, there was a significant improvement in the Murray score on day 5.
      CONCLUSIONS: Our results show that the use of MH combined with ERCC for 5 days
      accelerated the weaning process and ICU discharge.

PMID- 22964933
TI  - Clinical and pathological factors influencing the survival of breast cancer
      patients with malignant pleural effusion.
AB  - OBJECTIVE: The objective of this study was to identify the clinical and
      pathological factors that can influence the prognosis of breast cancer patients
      with clinical symptoms of malignant pleural effusion. METHODS: This was a
      clinical cohort study, in which we analyzed the medical charts of patients
      diagnosed with malignant pleural effusion between 2006 and 2010. By examining the
      charts, we identified the female patients with a history of breast cancer. For
      those patients, we collected pathology data related to the primary tumor and
      cytopathology data related to the pleural metastasis. RESULTS: We evaluated 145
      patients, 87 (60%) of whom had tested positive for malignant cells in the pleural
      fluid. Ductal histology was observed in 119 (82%). The triple-negative breast
      cancer phenotype was seen in 25 cases (17%). Those patients had the worst
      prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%)
      died during the follow-up period (through June of 2011). The mean survival after
      the identification of malignant pleural effusion was 6 months. CONCLUSIONS: In
      patients with triple-negative breast cancer who test positive for malignant cells
      in the pleural fluid, the prognosis is poor and survival is reduced.

PMID- 22964934
TI  - Emphysema index in a cohort of patients with no recognizable lung disease:
      influence of age.
AB  - OBJECTIVE: To investigate the effects of age on pulmonary emphysema, based on the
      values of the emphysema index (EI) in a cohort of patients who had never smoked
      and who had no recognizable lung disease. METHODS: We reviewed the CT scans,
      reported as normal, of 315 patients. Exclusion criteria were a history of
      smoking, cardiorespiratory disease, and exposure to drugs that could cause lung
      disease. From this cohort, we selected 32 patients (16 men and 16 women), matched
      for gender and body mass index, who were divided equally into two groups by age
      (< 50 years and > 50 years). We quantified emphysema using a computer program
      specific to that task. The EI was calculated with a threshold of -950 HU. We also
      evaluated total lung volume (TLV) and mean lung density (MLD). RESULTS: The
      overall means for TLV, MLD, and EI were 5,027 mL, -827 HU, and 2.54%,
      respectively. Mean values in the older and younger groups, respectively, were as
      follows: for TLV, 5,229 mL vs. 4,824 mL (p > 0.05); for MLD, -846 HU vs. -813 HU
      (p < 0.04); and for EI, 3.30% vs. 1.28% (p < 0.001). Significant correlations
      were found between EI and age (r = 0.66; p = 0.001), EI and TLV (r = 0.58; p =
      0.001), and EI and MLD (r = -0.67; p < 0.001). The predicted EI per age was
      defined by the regression equation (r2 = 0.43): p50(EI) = 0.049 * age - 0.5353.
      CONCLUSIONS: It is important to consider the influence of age when quantifying
      emphysema in patients over 50 years of age. Based on the regression analysis, EI
      values of 2.6%, 3.5%, and 4.5% can be considered normal for patients 30, 50, and
      70 years of age, respectively.

PMID- 22964935
TI  - Effectiveness of tuberculosis treatment.
AB  - OBJECTIVE: To analyze the treatment strategies that influence the effectiveness
      of tuberculosis treatment at primary care clinics (PCCs) in Brazil. METHODS: This
      was a descriptive, retrospective epidemiological survey based on the medical
      records of 588 tuberculosis patients enrolled in the tuberculosis control
      programs at two PCCs located in the city of Belem, Brazil: Centro de Saude Escola
      do Marco (CSEM) and Unidade Basica de Saude da Pedreira (UBSP). The survey was
      limited to patients enrolled between January of 2004 and December of 2008. We
      included only patients between 18 and 59 years of age, and we excluded those who
      were transferred or were found to have been misdiagnosed. We collected data
      regarding age, gender, type of treatment (self-administered or supervised), co
      infection with HIV, and treatment outcome. The health professionals involved in
      the tuberculosis control program at the two PCCs were interviewed regarding the
      strategies used for tuberculosis control and regarding routine clinical care for
      tuberculosis patients. RESULTS: There were no significant differences between the
      CSEM and UBSP patients regarding age, gender, and co-infection with HIV.
      Supervised treatment was used significantly more frequently and the rate of cure
      was higher at the CSEM than at the UBSP, whereas the rate of treatment
      noncompliance was higher at the UBSP than at the CSEM. CONCLUSIONS: For patients
      enrolled in tuberculosis control programs at PCCs in Brazil, supervised treatment
      appears to be an extremely important strategy for reducing the rate of treatment
      noncompliance.

PMID- 22964936
TI  - Tuberculosis, HIV, and poverty: temporal trends in Brazil, the Americas, and
      worldwide.
AB  - OBJECTIVE: To analyze the temporal trends of the incidence and prevalence of
      tuberculosis, with and without HIV co-infection, as well as of the associated
      mortality, in Brazil, the Americas, and worldwide. METHODS: We collected data
      related to tuberculosis, with and without HIV co-infection, between 1990 and
      2010, in Brazil, the Americas, and worldwide. Temporal trends were estimated by
      linear regression. RESULTS: We identified a trend toward a decrease in
      tuberculosis prevalence and mortality, and that trend was more pronounced in
      Brazil and the Americas than worldwide. There was also a trend toward an increase
      in the incidence of tuberculosis/HIV co-infection, as well as in the rates of
      detection of new cases of active and latent tuberculosis. The incidence of
      tuberculosis was found to trend downward in Brazil, whereas it trended upward
      worldwide. Tuberculosis incidence rates correlated positively with poverty rates
      and with HIV incidence rates. CONCLUSIONS: Social inequality and the advent of
      AIDS are the major factors that aggravate the current situation of tuberculosis.
      In this context, methodical approaches to the assessment of surveillance
      activities are welcome, because they will identify situations in which the
      reported tuberculosis data do not reflect the true incidence of this disease.

PMID- 22964937
TI  - Evolution of public policies and programs for asthma control in Brazil from the
      perspective of consensus guidelines.
AB  - There is much discussion about effective public policies that allow the proper
      treatment of asthma, providing care that is comprehensive and centered on asthma
      patients within their social context. Educating health professionals and asthma
      patients provides better recognition of symptoms and the triggers of asthma
      exacerbations, as well as disseminating strategies for avoiding such triggers,
      thereby ensuring better treatment and quality of life for asthma patients. Asthma
      imposes an ever-increasing burden on society, in terms of impaired quality of
      life, morbidity, and health care costs, making this a very important discussion
      in the field of public policy.

PMID- 22964938
TI  - Unilateral pulmonary agenesis.
AB  - Pulmonary agenesis is a rare congenital anomaly. We report the case of an 8-year
      old boy with left lung agenesis, without any other congenital malformations. When
      the patient presented symptoms, including cough, wheezing, and dyspnea, with no
      clinical improvement after a period of 30 days, imaging studies were conducted
      and the diagnosis was made.

PMID- 22964939
TI  - Pulmonary cryptosporidiosis in AIDS patients, an underdiagnosed disease.

PMID- 22964940
TI  - Activated charcoal bronchial aspiration.

PMID- 22964941
TI  - Lipoid pneumonia in a 40-day-old infant.

PMID- 22964944
TI  - Mutations of epigenetic regulators and of the spliceosome machinery in therapy
      related myeloid neoplasms and in acute leukemias evolved from chronic
      myeloproliferative diseases.

PMID- 22964943
TI  - A mechanistic study of the effect of doxorubicin/adriamycin on the estrogen
      response in a breast cancer model.
AB  - OBJECTIVE: Estrogen treatment limits the cytotoxic effects of chemotherapy in
      estrogen receptor-positive (ER+) breast cancer cell lines, suggesting that
      estrogen pathway signaling may confer chemotherapeutic resistance. This study
      investigates the molecular responses of ER+ breast cancer cell lines to the
      chemotherapeutic agent, doxorubicin, in the presence or absence of estrogen.
      METHODS: ER+ MCF-7 and T47-D cells were cultured in hormone-starved or estrogen
      containing media with or without doxorubicin at concentrations mimicking the low
      concentrations seen in plasma and tumor microenvironments in humans following
      typical bolus administration. Protein levels, phosphorylations, and interactions
      of estrogen-signaling molecules were assessed following these treatments, as well
      the effects of ER signaling inhibitors on cell proliferation. RESULTS:
      Surprisingly, estrogen and doxorubicin co-treatment markedly induced pro-growth
      alterations compared to doxorubicin alone and modestly enhanced estrogen alone
      induced changes. Several inhibitors suppressed cell proliferation in the presence
      of doxorubicin and estrogen. CONCLUSIONS: These findings demonstrate that
      molecular changes caused by doxorubicin in ER+ breast cancer cells can be
      reversed by estrogen, providing molecular evidence for the poorer responses of
      ER+ tumors to doxorubicin in the presence of physiologic estrogen levels. Our
      results also suggest that the addition of drugs targeting the ER, EGFR, the SFKs,
      MEK, PI3K, and/or the MMP proteins to a conventional chemotherapy regimen may
      improve chemosensitivity.

PMID- 22964945
TI  - Human soil-transmitted helminths:  implications of mass drug administration.
AB  - PURPOSE OF REVIEW: With the London Declaration on neglected tropical disease
      (NTD), we are entering a new era of combating NTDs. However, the worldwide
      prospects of increased mass drug administration (MDA) treatments warrant caution
      on the development of anthelmintic resistance. In this review, we discuss the
      practical implications of MDA programs on the development of anthelmintic
      resistance in human soil-transmitted helminths (STH). RECENT FINDINGS: There is
      poor evidence of anthelmintic resistance in human STH. Moreover, there is
      presumptive evidence that the refugia in MDA programs to control human STH is
      currently large, suggesting that the development of anthelmintic resistance in
      STH will be slow or may not occur. It remains unclear whether the current MDA
      strategy to control STH will sufficiently delay or prevent the development of
      anthelmintic resistance. First, differences in efficacy across and within STH
      species, and seasonal transmission of STH have not yet been considered. Second,
      any surveillance system to monitor drug efficacy is lacking. Finally, there is
      still no agreed strategy on how to deal with anthelmintic resistance once it
      emerges. SUMMARY: Although anthelmintic resistance in human STH is currently of
      limited concern, various actions should be put in place for its delay and
      monitoring, and strategies should be developed in case anthelmintic resistance
      occurs.

PMID- 22964946
TI  - Risks for infection in patients with myelodysplasia and acute leukemia.
AB  - PURPOSE OF REVIEW: The aim of the present review is to analyze the main
      parameters that may influence the onset of bacterial, fungal and viral infections
      in patients with myelodysplastic syndromes, acute myeloid leukemia and acute
      lymphoid leukemia. RECENT FINDINGS: The identification of factors influencing the
      onset of infections in high-risk patients is becoming one of the most important
      strategies to identify those patients who would really benefit from prophylactic
      and timely treatment. During the past few years several studies have been
      conducted to evaluate the impact of risk factors that may influence both the
      onset and the outcome of infections. The role of some of them is well defined
      (i.e. neutropenia, central venous catheters), whereas other factors are now
      emerging as new possible causative factors (i.e. iron overload, hospitalization).
      SUMMARY: Many factors have to be considered when evaluating the infectious risk
      in hematological patients. In current clinical practice the good knowledge of
      these factors may favor a better management of infectious risk, with a reduction
      of mortality rate.

PMID- 22964947
TI  - Invasive fungal infection in chronic granulomatous disease:  insights into
      pathogenesis and management.
AB  - PURPOSE OF REVIEW: Invasive fungal infections (IFIs) remain a major cause of
      death in patients with chronic granulomatous disease (CGD). We discuss the new
      insights into the pathogenesis, diagnosis, prevention, and management of invasive
      fungal infections in patients with CGD. RECENT FINDINGS: CGD has the highest
      prevalence of IFIs among the immunodeficiencies. Infections typically involve the
      lung, and the most commonly isolated pathogen is Aspergillus spp. However, IFIs
      due to rare opportunistic filamentous fungi are increasingly reported. Most IFIs
      are diagnosed on routine chest imaging, and serum markers such as galactomannan
      and 1,3-beta-D-glucan are of limited value in CGD. Routine use of itraconazole
      for prophylaxis continues to be recommended, although posaconazole may be an
      alternative. Management of IFIs is typically centered on prolonged courses of
      antifungal therapy. Surgery may be required for complete resolution, especially
      in the setting of osteomyelitis or infections due to Aspergillus nidulans or
      other poorly responsive molds. Hematopoietic stem cell transplantation (HSCT)
      cures CGD and may be appropriate in select patients with refractory IFIs.
      SUMMARY: Management of IFIs in CGD has significantly improved over the last
      decade. Earlier diagnosis of IFIs, accurate identification of pathogens, and
      development of reliable susceptibility testing are areas for future emphasis.
      HSCT is a promising therapy, even during refractory infections in CGD.

PMID- 22964948
TI  - Infusional beta-lactam antibiotics in febrile neutropenia:  has the time come?
AB  - PURPOSE OF REVIEW: Febrile neutropenia presents a clinical challenge in which
      timely and appropriate antibiotic exposure is crucial. In the context of altered
      pharmacokinetics and rising bacterial resistance, standard antibiotic doses are
      unlikely to be sufficient. This review explores the potential utility of altered
      dosing approaches of beta-lactam antibiotics to optimize treatment in febrile
      neutropenia. RECENT FINDINGS: There is a dynamic relationship between the
      antibiotic, the infecting pathogen, and the host. Great advancements have been
      made in the understanding of the pharmacokinetic changes in critical illness and
      the pharmacodynamic relationships of antibiotics in these settings. SUMMARY:
      Antibiotic treatment in febrile neutropenia is becoming increasingly difficult.
      Patients are of higher acuity, receive more intensive chemotherapy regimens
      leading to prolonged neutropenia, and are often exposed to multiple antibiotic
      courses. These patients display significant variability in antibiotic clearances
      and increases in volume of distribution compared with standard ward-based
      patients. Rising antibiotic resistance and a lack of new antibiotics in
      production have prompted alternative dosing strategies based on
      pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of
      beta-lactam antibiotics, to maximize the likelihood of treatment success. A
      definitive study that describes a mortality benefit of such dosing regimens
      remains elusive and the theoretical advantages require testing in well designed
      clinical trials.

PMID- 22964949
TI  - Diagnosis and management of prosthetic joint infection.
AB  - PURPOSE OF REVIEW: Prosthetic joint infection remains a devastating complication
      of arthroplasty associated with significant patient morbidity. The demand for
      arthroplasty is rapidly growing with a corresponding increase in the number of
      infections involving the prosthesis. The diagnosis and treatment of prosthetic
      joint infections presents a significant challenge to orthopaedic and infectious
      diseases clinicians. RECENT FINDINGS: The underlying pathogenesis of prosthetic
      joint infections is due to the ability of the microorganisms to form a biofilm.
      The biofilm provides protection against host immune responses and antimicrobial
      therapy. In addition, it impedes standard laboratory diagnostic techniques. This
      review will examine new investigations to improve the diagnostic yield and
      rapidity of diagnosis of infections, including the use of sonication to disrupt
      the biofilm, new molecular tests to improve the detection of infecting
      microorganisms and new imaging techniques such as (18)F-fluoro-deoxyglucose PET.
      SUMMARY: The successful treatment of prosthetic joint infections is dependent on
      eliminating the biofilm dwelling microorganisms whilst maintaining patient
      mobility and quality of life. This review will examine current understanding of
      management approaches for these infections, with a particular focus on
      antimicrobial therapy with activity against the biofilm, such as rifampicin and
      fluoroquinolones.

PMID- 22964950
TI  - Oral pharmacokinetic comparison of different genistein tablets in beagle dogs.
AB  - An accurate and sensitive analytical method has been developed for the
      quantification of genistein in dog plasma using high-performance liquid
      chromatography/tandem mass spectrometry. Genistein and diclofenac (internal
      standard) were extracted from the plasma sample using methyl tert-butyl ether and
      then separated on an Agilent Zorbax C18 column using a gradient mobile phase. The
      detector was a Q-trap mass spectrometer with an electrospray ionization interface
      operating in the multiple reaction monitoring mode. The assay was linear over the
      concentration range of 0.10-500 ng/mL with a lower limit of quantification of
      0.10 ng/mL. The method was shown to be reproducible and reliable, with inter-day
      and intra-day accuracy and precision within +/-15%. The method was successfully
      applied to a pharmacokinetic comparison of immediate and extended release tablets
      in beagle dogs after oral administration. Immediate release tablets showed rapid
      genistein absorption, with mean peak concentration of 726 +/- 199 ng/mL reached
      at 0.2 +/- 0.0 h. However, the absorption of genistein was considerably slower
      and more sustainable for extended release tablets. The relative bioavailability
      of the extended release tablet over the immediate release formulation was
      estimated to be 134 +/- 47% based on the AUCInf values from non-compartmental
      analysis.

PMID- 22964951
TI  - Analysis of essential oils and fatty acids from Platycodi Radix using chemometric
      methods and retention indices.
AB  - The chemical composition of the essential oils and fatty acids among nine groups
      of Platycodi Radix in China was analyzed by gas chromatography-mass spectrometry.
      Complicated components were resolved using chemometric methods. Simultaneously,
      the various features among heuristic evolving latent projections, selective ion
      analysis and alternative moving window factor analysis were compared by using
      some experimental data. Temperature-programmed retention indices were applied in
      further identification of the chemical composition of the essential oils. The
      equivalent chain length, fraction chain length, and an established special
      retention indices library integrated with mass spectrometry were also applied to
      further identify the composition of fatty acids, including total fatty acids,
      esterified fatty acids and free fatty acids. A total of 121 different compounds
      accounting for 95.12-98.74% were identified among the essential oils. Chemical
      polymorphisms and variation existed in the essential oils of Platycodi Radix.
      Sixteen components were identified in fatty acids, and linoleic acid (18:2n-6c)
      and other unsaturated acid possess a characteristic majority.

PMID- 22964952
TI  - Large cell neuroendocrine carcinoma of the ampulla of Vater.
AB  - CONTEXT: Large cell neuroendocrine carcinomas of the ampulla of Vater are rare
      and confer a very poor prognosis despite aggressive therapy. There are few case
      reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the
      literature and to date no studies have been done to establish optimal management.
      We describe a pooled case series from published reports of neuroendocrine
      carcinomas of the ampulla of Vater including a case which presented to our
      institution. METHODS: A narrative review was undertaken including all published
      English case reports of large cell neuroendocrine carcinomas of the ampulla of
      Vater. Our primary outcome was to determine the overall survival. RESULTS: Twenty
      cases of large cell neuroendocrine carcinomas of the ampulla of Vater were
      identified. Seventy-six percent of patients were reported to have died of disease
      with a mean survival of 11.8 months. Twenty percent of the tumours were
      associated with an adenoma. The approximate median survivals were 15 months for
      those with an associated adenoma and 11 months without. CONCLUSIONS: This pooled
      analysis demonstrates both the rarity and poor prognosis of large cell
      neuroendocrine carcinomas of the ampulla of Vater. Although surgical resection is
      the mainstay of treatment, we review common adjuvant chemotherapy regimes.
      Prognosis may be improved when these tumours are associated with adenomas,
      however, further studies are needed.

PMID- 22964953
TI  - Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 1: basic
      studies.
AB  - CONTEXT: Porcine pancreatic enzymes (PPE) extracted from glandular stomach has
      been used for the treatment of pancreatic cancer patients. Unfortunately, no
      information is available on the in vitro and in vivo effect on the pancreas and
      other tissues. OBJECTIVE: We used Syrian Golden hamsters, a unique pancreatic
      cancer model, to obtain basic information on PPE for its eventual use for the
      treatment of pancreatic cancer. DESIGN: PPE was used in different concentrations
      in vitro and in vivo. The stability of the enzyme in the water solution was
      investigated. It was given to the hamsters by gavage in concentrations of 1g/kg
      and 400 mg/kg for short periods and in aqueous solution for 65 days. Plasma
      enzyme and insulin, the size of islets and the number of the insulin cells per
      islet were examined. RESULTS: The enzyme activity of PPE was maintained in water
      solution for at least 24 hours. Due to its content of calcium chloride it showed
      a high toxicity to normal and malignant hamster pancreatic cancer cells and human
      pancreatic cancer cell lines in vitro. PPE did not alter the plasma pancreatic
      enzyme levels regardless of the dose, duration and application route. On the
      contrary, PPE reduced their levels significantly. Remarkably, it also reduced the
      level of insulin, the size of the islets and the number of insulin cells in the
      islets significantly. CONCLUSION: The results imply that PPE does not enter the
      blood circulation but it appears to slow down the function of both the exocrine
      and endocrine pancreas.

PMID- 22964954
TI  - Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 2:
      carcinogenesis studies.
AB  - CONTEXT: Our previous study suggested that porcine pancreatic extract in hamsters
      with peripheral insulin resistance, normalizes insulin output, islet size and
      pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic
      cancer cells in nude mice. OBJECTIVE: To examine the potential value of the
      porcine pancreatic extract in controlling pancreatic carcinogenesis in this
      model, the present experiment was performed. DESIGN: Hamsters were fed a high fat
      diet and four weeks later when insulin resistance emerges, they were divided into
      two groups. One group received 1 g/kg BW of porcine pancreatic extract in
      drinking water and the other group received tap water. One week later, when
      insulin output normalizes in porcine pancreatic extract-treated hamsters, a
      single subcutaneous injection of N-nitrosobis-(2-oxopropyl) amine (BOP) at a dose
      of 40 mg/kg BW was given to all hamsters. The experiment was terminated at 43
      weeks after the porcine pancreatic extract treatment. The number and size of
      pancreatic tumors, blood glucose, insulin, amylase and lipase levels, the average
      size of islets and the number of insulin cells/islets were determined. RESULTS:
      The incidence of pancreatic cancer was significantly lower in the porcine
      pancreatic extract group (P=0.043), as well as the plasma insulin level and the
      size of the islets in the porcine pancreatic extract group were significantly
      lower (P<0.001) than in the control group. No significantly differences were
      found in the glucose level between the groups. CONCLUSION: These results show
      that porcine pancreatic extract has a potential to inhibit pancreatic cancer
      growth.

PMID- 22964955
TI  - Reduction in delayed gastric emptying following non-pylorus preserving
      pancreaticoduodenectomy by addition of a Braun enteroenterostomy.
AB  - CONTEXT: Delayed gastric emptying is a major cause of morbidity following
      pancreaticoduodenectomy. OBJECTIVE: The impact of a Braun enteroenterostomy on
      delayed gastric emptying, used in reconstruction following classic
      pancreaticoduodenectomy, was assessed. PATIENTS: Forty-four consecutive patients
      undergoing non-pylorus preserving pancreaticoduodenectomy from 2009 to 2011 by a
      single surgeon were included in this study. INTERVENTIONS: The first 20 patients
      had a standard antecolic gastroenterostomy and the subsequent 24 had the addition
      of a Braun enteroenterostomy. RESULTS: Patient characteristics, the extent of
      surgery, surgical findings and tumor characteristics were similar between the two
      groups. The delayed gastric emptying rate in the Braun enteroenterostomy (1/24,
      4.2%) was significantly lower (P=0.008) than the standard reconstruction group
      (7/20, 35.0%). In the standard group, 6 of 7 cases (85.7%) of delayed gastric
      emptying were class C in nature. After exclusion of 8 total pancreatectomy
      patients, the pancreatic fistula rate in the Braun enteroenterostomy group (4/19,
      21.1%) was similar (0.706) to the standard reconstruction group (5/17, 29.4%) as
      was the median length of hospital stay (10 days vs. 15 days; P=0.291). Braun
      enteroenterostomy technique was the only significant independent factor
      associated with reduced delayed gastric emptying with an odds ratio of 0.08 (95%
      confidence interval: 0.01-0.73; P=0.025). CONCLUSION: The use of Braun
      enteroenterostomy following non-pylorus preserving pancreaticoduodenectomy
      appears to result in a significant reduction in delayed gastric emptying.

PMID- 22964956
TI  - Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma.
AB  - CONTEXT: Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan,
      fluorouracil, and leucovorin) was shown to be effective in a large phase III
      trial. OBJECTIVE: The purpose of this study was to examine the tolerance and
      effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical
      trial and to document any dose modifications used by practicing oncologists.
      METHODS: Data on patients with all stages of pancreatic adenocarcinoma treated
      with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and
      use of any dose modifications. RESULTS: Total of 61 patients was included in this
      review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and
      majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight
      (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally
      advanced or borderline resectable disease. Patients were treated with a median
      number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302)
      of all cycles. Ten patients had stable disease (16.4%), four had a partial
      response (6.6%) while eight had progressive disease (13.1%) on best imaging
      following therapy. Median progression-free survival and overall survival were 7.5
      months and 13.5 months, respectively. The most common grade 3-4 adverse event was
      neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia.
      Twenty-one patients (34.4%) were hospitalized as a result of therapy but there
      were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually
      discontinued as a result of adverse events. CONCLUSION: Despite substantial rates
      of adverse events and use of dose modifications, FOLFIRINOX was found to be
      clinically effective in both metastatic and non-metastatic patients. Regimen
      toxicity did not detract from overall response and survival.

PMID- 22964957
TI  - Two avirulent, lentogenic strains of Newcastle disease virus are cytotoxic for
      some human pancreatic tumor lines in vitro.
AB  - CONTEXT: Pancreatic cancer is the fourth leading cause of cancer death in the
      U.S. Highly infectious Newcastle disease virus (NDV) strains are known to be very
      cytotoxic for an array of human tumor cell types in vitro and in vivo but the
      effects of these and avirulent NDV strains on pancreatic neoplasms are little
      known. OBJECTIVE: Here, the direct cytolytic effects of the avirulent Hitchner-B1
      (B1) and Ulster (U) NDV strains on 7 human pancreatic tumor cell lines and 4
      normal human cell lines were studied. METHODS: Cytotoxicity assays used serially
      diluted NDV to determine minimum cytotoxic plaque forming unit (PFU) doses.
      RESULTS: For NDV-B1, normal human cells were killed only by relatively high doses
      (range: 471-3,724 PFU) whereas NDV-U killed these cells at low PFU (range: 0.32
      1.60 PFU). Most pancreatic cancer cell types were killed by much lower NDV-B1
      doses (range: 0.40-2.60 PFU) while NDV-U killed Capan-1 and SU.86.86 cultures at
      very low doses (0.00041 PFU and 0.0034 PFU, respectively). CONCLUSIONS: On
      average, 1,555 times more NDV-B1 was needed to kill normal cells than most
      pancreatic tumor cells and 558 times more NDV-U to kill the two most sensitive
      pancreatic cancer lines. These innately-targeted lentogenic viruses may have
      meaningful potential in treating pancreatic cancer.

PMID- 22964958
TI  - Pilot study of aprepitant for prevention of post-ERCP pancreatitis in high risk
      patients: a phase II randomized, double-blind placebo controlled trial.
AB  - CONTEXT: Animal studies have demonstrated a role for substance P binding to
      neurokinin-1 receptor in the pathogenesis of acute pancreatitis. OBJECTIVE: Our
      aim was to assess the efficacy of a neurokinin-1 receptor antagonist (aprepitant)
      at preventing post-ERCP pancreatitis in high risk patients. DESIGN: Randomized,
      double-blind, placebo controlled trial at a single academic medical center.
      INTERVENTION: Patients at high risk for post-ERCP pancreatitis received either
      placebo or oral aprepitant administered 4 hours prior to ERCP, 80 mg 24 hours
      after the first dose, and then 80 mg 24 hours after the second dose. PATIENTS:
      Thirty-four patients received aprepitant and 39 patients received placebo.
      STATISTICS: Fisher's exact test was used to compare incidence of post-ERCP
      pancreatitis in the two groups. RESULTS: Baseline characteristics were similar
      between the two groups. Incidence of acute pancreatitis was 7 in the aprepitant
      group and 7 in the placebo group. Hospitalization within 7 days post-procedure
      for abdominal pain that did not meet criteria for acute pancreatitis occurred in
      6 and 9 patients in the aprepitant and placebo groups respectively (P=0.772).
      CONCLUSIONS: Aprepitant did not lower incidence of post-ERCP pancreatitis in this
      preliminary human study. Larger studies potentially using the recently available
      intravenous formulation are necessary to conclusively clarify the efficacy of
      aprepitant in this setting.  

PMID- 22964959
TI  - Morphological and functional alterations of small intestine in chronic
      pancreatitis.
AB  - CONTEXT: The small intestine in chronic pancreatitis has not been investigated
      yet thoroughly. It would be important to understand fat metabolism in the course
      of this disease and could be explained if the small intestine has some
      pathological conditions and, due to this reason, pancreatic enzyme substitution
      does not work in all patients. OBJECTIVE: To investigate the pathophysiology of
      small intestine in chronic pancreatitis and to show the reason why in some cases
      pancreatic enzyme substitution does not work properly. PATIENTS: In the process
      of the study 33 chronic pancreatitis patients have been examined. CONTROLS: The
      control group includes 30 subjects without chronic pancreatitis similar for age,
      sex and alcohol consumption to the patients with chronic pancreatitis patients.
      INVESTIGATIONS: Aspiration biopsy of jejunum mucosa followed by histological
      examination and investigation of intestinal enzymes by aspiration has been
      performed. MAIN OUTCOME MEASURES: Metabolism at membranic level has been studied
      by enzymatic activity of amylase and lipase in the small intestine. Production of
      enzymes (monoglyceride lipase, lactase, saccharase, maltase, glycyl-l-leucine
      dipeptidase) promoting metabolism in enterocytes has been estimated as to their
      activity in homogenates of jejunum mucosa samples. Participation of mucosa in
      intestinal digestion has been assessed by alkaline phosphatase activity in a
      secretory chyme from proximal portion of jejunum. Absorptive capacity of jejunum
      was evaluated by D-xylose test results. DNA, lysozyme, immunoglobulin contents of
      chyme have also been calculated and bacteriological study of chyme has been also
      performed. RESULTS: Secondary enteritis, accompanied by moderate dystrophic
      changes of mucous membrane, thinning of limbus, and decrease of Paneth cell
      mitotic index, was found to occur in chronic pancreatitis patients. Enteritis is
      followed by changes in enzymatic processes in the sphere of membrane and
      intestinal digestion, decrease of absorption, accelerated desquamation of
      epithelium, fall in local immunity and development of bacterial overgrowth
      syndrome. CONCLUSIONS: Existence of secondary enteritis and bacterial overgrowth
      syndrome validates lack of enzyme replacement therapy efficacy in some chronic
      pancreatitis patients with pancreatic insufficiency. To optimize treatment in
      such cases it is important to perform small intestine decontamination and
      escalate enzyme preparation dosage.

PMID- 22964960
TI  - Aggressive surgical management of recurrent lymph node and pancreatic head
      metastases of resected fibrolamellar hepatocellular carcinoma: a case report.
AB  - CONTEXT: Fibrolamellar hepatocellular carcinoma is a rare liver tumor with the
      propensity to metastasize to the lymph nodes months or years after initial
      surgery. However, its metastatic spread to the pancreas was previously reported
      only in a child. CASE REPORT: We present an unusual case of a young female
      patient who was repeatedly treated by surgical excision of abdominal and
      mediastinal lymph node recurrences between 2 and 6 years after left hepatic
      lobectomy for fibrolamellar hepatocellular carcinoma. At 8 years following her
      initial surgery, the patient was diagnosed with pancreatic head metastasis and a
      pancreaticoduodenectomy was performed. Postoperative course was uneventful and
      the patient did not experience recurrence within the last 18 months. CONCLUSION:
      The metastasis of fibrolamellar hepatocellular carcinoma to the pancreas is
      highly exceptional but possible and its excision appears warranted as well.

PMID- 22964961
TI  - Celiac disease presenting as recurrent pancreatitis and pseudocyst.
AB  - CONTEXT: The association between celiac disease and pancreatitis is sparsely
      reported. Celiac disease may remain asymptomatic or may have atypical features,
      and its diagnosis in pancreatitis may not be obvious. It is more than mere chance
      association that explains the occurrence of pancreatitis in celiac disease.
      Malnutrition, papillary stenosis and immunopathogenetic mechanisms contribute to
      the development of pancreatitis in a patient of celiac disease. CASE REPORT: We
      here report one such case that had recurrent acute pancreatitis with pseudocyst
      formation and negative routine etiological work up. It was on noticing abnormal
      duodenal mucosa at the time of doing endoscopic cystogastrostomy that the
      diagnosis of celiac disease was suspected and later proved. CONCLUSION: This
      report highlights that celiac disease should be considered in the etiological
      work up of patients with unexplained pancreatitis.

PMID- 22964962
TI  - Synchronous presentation of ampullary adenocarcinoma and common bile duct cancer:
      report of a case and review of literature.
AB  - CONTEXT: Ampullary adenocarcinomas and bile duct cancers represent a very small
      minority of all gastrointestinal malignancies. Synchronous presentation of both
      malignancies is extremely rare. CASE REPORT: We report a case of a 76-year-old
      male who presented with painless jaundice. His work-up showed an ampullary mass
      and a separate common bile duct stricture. Attempted endoscopic resection
      established the diagnosis of ampullary adenocarcinoma. Pathologic examination of
      the Whipple specimen identified a separate focus of bile duct cancer. CONCLUSION:
      Synchronous presentation of an ampullary mass and separate distal bile duct
      stricture, especially in elderly patients, should raise concern for both lesions
      representing malignancies. In the absence of conclusive evidence for survival
      advantage in resected early stage ampullary and biliary cancers, close
      observation should be considered a valid alternative to adjuvant chemotherapy and
      radiation.

PMID- 22964963
TI  - Pancreatitis during treatment with liraglutide.

PMID- 22964964
TI  - Lesson from acute experimental pancreatitis: multidrug strategies is effective
      than single-target therapy.

PMID- 22964965
TI  - IPMN and parathyroid adenoma: an interesting association.

PMID- 22964966
TI  - Competing time-to-event endpoints in cardiology trials: a simulation study to
      illustrate the importance of an adequate statistical analysis.
AB  - BACKGROUND: Clinical trials in cardiology commonly consider time-to-event
      endpoints that are often influenced by competing risks. In the presence of
      competing risks, standard survival analysis techniques, such as the Kaplan-Meier
      estimator, can yield seriously biased results. Although methods to account for
      competing risks are well known in the statistical literature, they are rarely
      applied in clinical trials. DESIGN: Simulation study, to demonstrate the
      appropriate application and interpretation of the competing risks methodology
      with respect to time-to-event endpoints. METHODS: In this paper, different
      statistical approaches to account for competing risks are systematically
      compared, based on a simulation study and using the original data from a
      cardiology trial. RESULTS: Group comparisons in clinical trials that have
      competing time-to-event endpoints should be based on the cause-specific hazard
      functions. In contrast, group comparisons based on event rates should be carried
      out with care, as event rates are directly influenced by competing events.
      CONCLUSION: Ignoring or not fully accounting for competing risks may yield
      misleading or even erroneous results, which could hinder understanding of
      survival trends; therefore, it is important that competing risks methodology be
      routinely incorporated into clinical trial standards.

PMID- 22964967
TI  - Changes in serum levels of cartilage oligomeric matrix protein after estrogen and
      alendronate therapy in postmenopausal women.
AB  - BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint
      destruction and its serum levels are used for assessing therapeutic efficacy.
      This study aims to compare changes in serum COMP levels in postmenopausal women
      with osteopenia/osteoporosis receiving estrogen and alendronate. METHODS: A total
      of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated
      with either estrogen (17beta-estradiol 1 mg, n = 30) or bisphosphonate
      (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal
      women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and
      after 6 months of treatment. RESULTS: Estrogen decreased levels of COMP at 6
      months compared to baseline levels (-8.35 +/- 19.38%), whereas the bisphosphonate
      and control groups resulted in no significant changes (-5.50 +/- 18.69 and -1.49
      +/- 25.34%, respectively). Concentrations of osteocalcin decreased significantly
      in both treatment groups (estrogen -25.60 +/- 24.42% and alendronate -13.76 +/-
      23.89%, respectively). There was a significant positive correlation between
      changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002).
      CONCLUSIONS: Postmenopausal women treated with estrogen showed significantly
      decreased levels of COMP after 6 months. Estrogen might provide a further
      treatment modality in the prevention of joint destruction.

PMID- 22964968
TI  - Lithium diffusion in lithium nitride by pulsed-field gradient NMR.
AB  - Lithium self-diffusion coefficients are measured for the first time using (7)Li
      Pulsed-Field Gradient Nuclear Magnetic Resonance (PFG-NMR) in a crystalline
      inorganic powder of alpha-Li(3)N between 534 K and 774 K. The diffusion of
      lithium cations is anisotropic, and the activation energy for the diffusion
      within the Li(2)N layers was found to be 0.150 +/- 0.009 eV.

PMID- 22964969
TI  - Kinetics of serum brain-derived neurotrophic factor following low-intensity
      versus high-intensity exercise in men and women.
AB  - Physical activity has been shown to enhance circulating brain-derived
      neurotrophic factor (BDNF) in animals and humans. However, the exact time course
      and sex-specific modulation of peripheral BDNF in response to exercise are still
      poorly understood. We examined the kinetics of BDNF serum concentrations in
      response to perceived high-intensity and low-intensity exercise, and during a
      subsequent recovery period by taking several blood samples during each phase.
      Furthermore, we compared the BDNF concentration between young men and women
      taking oral contraceptives. We found transient BDNF elevations during physical
      activity only for the high-intensity condition. Here, BDNF reached its maximum
      serum concentration after 20 min of exercise, and returned to baseline after
      approximately 10 min of recovery. Although there were no sex differences during
      baseline or recovery, the increase in the BDNF concentration during the exercise
      phase was more pronounced in men than in women.

PMID- 22964970
TI  - Superinduction of leptin mRNA in mouse hypothalamic neurons.
AB  - In marked contrast to several other species, including rats and humans, leptin
      gene expression is undetectable in mouse brain. This unexpected finding may
      reflect unique energy regulation pathways in the mouse. We investigated possible
      mechanisms by which leptin (ob) gene expression is suppressed in mouse brain: (a)
      the possibility that ob mRNA levels might be detectable in vitro through the
      superinduction of gene expression following protein synthesis inhibition and (b)
      whether chromatin modification of the ob gene was responsible for this
      repression. Experiments were conducted on mouse hypothalamic neurons in vitro.
      Cells were treated with (a) protein synthesis inhibitors: cycloheximide (CHX; 25
      ug/ml); puromycin (50 ug/ml); anisomycin (5 uM); (b) trichostatin A (histone
      deacetylase inhibitor; 500 nM); and (c) 5-aza-2'-deoxycytidine (DNA methylation
      inhibitor; 5 uM). Following the incubations, cells were harvested for the
      preparation of RNA and ob mRNA was detected using real-time reverse transcription
      PCR. Protein synthesis inhibitors induced a rapid increase in ob mRNA levels in
      mouse hypothalamic neurons in vitro. For example CHX stimulation of ob mRNA was
      detectable at 60 min after treatment and reached a maximum between 4 and 6 h. A
      dose-response analysis, with concentrations of CHX of 1, 2, 10, 25, and 50
      MUg/ml, indicated that CHX was already effective at 1.0 MUg/ml, with a maximal
      effect by 25 MUg/ml. In contrast, incubation with trichostatin A and 5-aza-2'
      deoxycytidine had no effect and ob mRNA remained undetectable. These data show
      that leptin gene expression is superinduced in ob-negative mouse hypothalamic
      neurons following inhibition of protein synthesis. They confirm that the
      previously reported absence of leptin mRNA in mouse brain is probably because of
      an active repressive mechanism, although this may not involve chromatin
      modification.

PMID- 22964971
TI  - Reported visual imagery and apparent motion:  an event-related potential study.
AB  - A previous behavioral study showed that a group of individuals with high
      vividness of visual imagery (High group), as determined from the score for the
      Vividness of Visual Imagery Questionnaire (VVIQ), could perceive the apparent
      motion path more strongly than a group of individuals with low vividness of
      visual imagery (Low group). To examine the physiological differences underlying
      these differences in perception, we compared the brain activity during an
      apparent motion task for the High and the Low groups using
      electroencephalography. We initially screened 60 potential participants using the
      VVIQ. On the basis of their scores, we invited 20 people from the lower and the
      higher ends of the VVIQ distribution to participate in our event-related
      potential study. Our results showed that individuals in both the High and the Low
      groups were sensitive to the apparent motion content of the task. Perception of
      apparent motion evoked a negative potential starting around 90 ms, followed by a
      positive potential beginning at 150-170 ms after the second stimulus. The scalp
      distributions of both negative and positive potentials for the High group were
      broader than those for the Low group. Moreover, the onset of positivity in the
      High group (150 ms) was earlier than that in the Low group (170 ms). We believe
      that these results may be mechanistically associated with the differences in the
      perception of apparent motion between individuals with high and low vividness of
      visual imagery.

PMID- 22964972
TI  - Neural substrate for facilitation of pain processing during sadness.
AB  - It is well known that emotion can modify the experience of pain. However, it is
      unclear how an emotional state and its concomitant neural activity affects
      activity in brain regions responsive to pain, thus altering the experience of
      pain itself. In this study, we examined the effect of sad mood on perception of
      painful stimuli and used functional MRI (fMRI) to identify neural activity
      changes in 15 participants who, in separate trials, (a) received painful electric
      shocks; (b) experienced a sad mood; and (c) received electric shocks as they were
      experiencing a sad mood. Sad mood was induced using a previously validated
      paradigm using sad pictures. As predicted, participants rated pain as more
      intense when they were experiencing a sad mood (viewing sad pictures) than when
      they were viewing neutral pictures, even though the intensity of the painful
      stimulation was identical under both conditions. Analysis of fMRI data showed
      that when pain was delivered while participants were feeling sad, neural
      activation was significantly greater in some areas known to process pain
      information as well as some that are believed to primarily process emotion. The
      'pain-processing' areas included the secondary somatosensory cortex and the
      adjacent posterior insula (pIn/SII) as well as periaqueductal gray. The
      'emotional-processing' regions included the subgenual cingulate cortex and the
      amygdala. On the basis of these results, we suggest that increased activation in
      the pIn/SII is part of a top-down system of pain facilitation that includes the
      anterior cingulate cortex, amygdala, and periaqueductal gray.

PMID- 22964973
TI  - Light fractionation significantly improves the response of superficial basal cell
      carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a
      randomized, prospective trial.
AB  - Photodynamic therapy (PDT) using topical porphyrin-precursors is a promising
      treatment for superficial basal cell carcinoma (sBCC), but it needs further
      optimization. The aim of this study was to compare 5-year lesion (complete)
      response rates of sBCC treated with topical aminolaevulinic acid (ALA)-PDT using
      a single illumination vs. ALA-PDT using a 2-fold illumination scheme. A
      prospective, randomized study was performed, in which 91 patients with 299
      lesions were treated with a 2-fold illumination scheme with 2 light fractions of
      20 and 80 J/cm2 delivered 4 and 6 h after a single application of 20% ALA, and
      106 patients with 274 lesions were treated with a single illumination of 75 J/cm2
      4 h after a single application of 20% ALA. All lesions were treated at a fluence
      rate of 50 mW/cm2. An interim time to event analysis of complete response (CR)
      rates at 12 months showed encouraging results, and therefore lesions were
      followed for 5 years post-therapy. A third group of 50 patients with 172 lesions
      treated with 2-fold illumination were included after the initial period and
      analysed separately. The CR rate was significantly greater following the 2-fold
      illumination than the single illumination (p = 0.0002, log-rank test). Five years
      after therapy the CR rate after 2-fold illumination was 88%, whereas the CR rate
      after single illumination was 75%. The CR rate in the third group of lesions,
      treated with 2-fold illumination was 97% and 88% at 12 months and 5 years after
      therapy, respectively. Long-term follow-up indicates superior efficacy in sBCC of
      ALA-PDT with 2-fold illumination compared with ALA-PDT with single illumination.

PMID- 22964974
TI  - Primary open-angle glaucoma vs normal-tension glaucoma: the vascular perspective.
AB  - OBJECTIVE: To compare and contrast the presence of ocular and systemic vascular
      function in patients with newly diagnosed and previously untreated primary open
      angle glaucoma (POAG) vs those with normal-tension glaucoma (NTG) and comparable
      early-stage, functional loss. METHODS: The systemic vascular function of 19
      patients with POAG, 19 patients with NTG, and 20 healthy individuals serving as
      controls was assessed using 24-hour ambulatory blood pressure monitoring,
      peripheral pulse-wave analysis, and carotid intima-media thickness. Retinal
      vascular reactivity to flicker light was assessed using dynamic retinal vessel
      analysis (Imedos, GmbH). RESULTS: Compared with controls, patients with POAG and
      those with NTG exhibited similarly increased nocturnal systemic blood pressure
      variability (P = .01), peripheral arterial stiffness (P = .02), carotid intima
      media thickness (P = .04), and reduced ocular perfusion pressure (P < .001).
      Furthermore, on dynamic retinal vessel analysis, both glaucoma groups exhibited
      steeper retinal arterial constriction slopes after cessation of flicker (P =
      .007) and a similarly increased fluctuation in arterial and venous baseline
      diameter (P = .008 and P = .009, respectively) compared with controls.
      CONCLUSIONS: Patients with POAG or NTG exhibit similar alterations in ocular and
      systemic circulation in the early stages of their disease process. This finding
      highlights the importance of considering vascular risk factors in both conditions
      and raises questions about the current separation of the two conditions into
      distinct clinical entities.

PMID- 22964975
TI  - Pioglitazone ameliorates endothelial dysfunction in those with impaired glucose
      regulation among the first-degree relatives of type 2 diabetes mellitus patients.
AB  - OBJECTIVE: To study the effects of pioglitazone on endothelial dysfunction of
      subjects with impaired glucose regulation (IGR) among the first-degree relatives
      of patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: The first
      degree relatives of T2DM patients were screened with oral glucose test and IGR
      was diagnosed. IGR subjects whose blood glucose was still above the level after 1
      month exercise were randomized to receive pioglitazone (15 mg/day) or vehicle for
      12 weeks. Endothelial function was assessed as endothelium-dependent and 
      independent vasodilation. Blood nitric oxide (NO), blood pressure, body mass
      index, insulin and serum lipids were also measured. Area under the curve of
      glucose (AUC(glu)) and insulin (AUC(INS)), homeostasis model assessment of
      insulin resistance (HOMA-IR), HOMA of beta-cell function (HOMA-beta) and early
      insulin secretion index (DeltaI(30)/DeltaG(30)) were calculated. RESULTS: After
      pioglitazone treatment, fasting plasma, 2-hour plasma glucose, triglyceride (TG),
      fasting insulin, AUC(glu), HOMA-beta and HOMA-IR, 2-hour insulin, AUC(INS) and
      DeltaI(30)/DeltaG(30) decreased. Endothelium-dependent vasodilation and NO were
      significantly improved in the treatment group. Furthermore, the changes of
      endothelium-dependent vasodilation were negatively correlated with changes in
      AUC(INS) but positively with NO and HOMA-beta. Stepwise multivariate regression
      analysis showed that changes in NO and HOMA-beta were both independent parameters
      for improvement of endothelial dysfunction. CONCLUSION: Pioglitazone decreased
      blood glucose and TG, increased insulin sensitivity, and ameliorated endothelial
      dysfunction of IGR subjects among the first-degree relatives of T2DM patients.
      Increased NO production may be associated with the improvement of endothelial
      dysfunction.

PMID- 22964976
TI  - Risk factor, age and sex differences in chronic kidney disease prevalence in a
      diabetic cohort: the pathways study.
AB  - BACKGROUND/AIMS: Women with diabetes experience a disproportionately greater
      burden of diabetic kidney disease (DKD) risk factors compared to men; however,
      sex-specific differences in DKD are not well defined. The effect of age on sex
      differences in DKD is unknown. METHODS: We performed a cross-sectional analysis
      of the prevalence of DKD (eGFR <60 ml/min/1.73 m(2) or microalbuminuria),
      advanced DKD (eGFR <30 ml/min/1.73 m(2)), and common DKD risk factors in the
      Pathways Study (n = 4,839), a prospective cohort study of diabetic patients from
      a managed care setting. Subjects were stratified by age <60 and >=60 years to
      examine for differences by age. Logistic regression models examined the
      association between sex and prevalence of DKD and risk factors. RESULTS: Women of
      all ages had 28% decreased odds of DKD (OR 0.72, 95% CI 0.62-0.83); however, they
      had a greater prevalence of advanced DKD (OR 1.67, 95% CI 1.05-2.64),
      dyslipidemia (OR 1.42, 95% CI 1.16-1.74), and obesity (OR 1.87, 95% CI 1.60-2.20)
      compared to men. Women had similar odds of hypertension and poor glycemic control
      as men. Women >=60 years had increased odds of advanced DKD, hypertension,
      dyslipidemia, and obesity compared to similarly aged men. Women <60 years had
      increased odds of obesity compared to their male counterparts. CONCLUSION: Women
      with diabetes had an increased prevalence of advanced DKD and common DKD risk
      factors compared to men and these disparities were most prominent amongst the
      elderly.

PMID- 22964978
TI  - High efficiency enrichment of low-abundance peptides by novel dual-platform
      graphene@SiO2@PMMA.
AB  - For the first time, dual-platform graphene@SiO(2)@poly(methyl methacrylate)
      (PMMA) material was synthesized, and successfully applied to efficiently enrich
      low-abundance peptides for mass spectrometry analysis.

PMID- 22964977
TI  - The yeast THO complex forms a 5-subunit assembly that directly interacts with
      active chromatin.
AB  - The THO complex is a nuclear structure whose architecture is conserved among all
      kingdoms and plays an important role in mRNP biogenesis connecting transcription
      elongation with mRNA maturation and export. Recent data indicates that the THO
      complex is necessary for the proper expression of some genes, assurance of
      genetic stability by preventing transcription-associated recombination. Yeast THO
      has been described as a heterotetramer (Tho2, Hpr1, Mft1 and Thp2) that performs
      several functions through the interaction with other proteins like Tex1 or the
      mRNA export factors Sub2 and Yra1, with which it forms the TRanscription and
      EXport complex (TREX). In this article we review the cellular role of THO, which
      we show to be composed of five subunits with Tex1 being also an integral part of
      the complex. We also show a low-resolution structure of THO and localize some of
      its components. We discuss the consequences of THO interaction with nucleic acids
      through the unfolded C-terminal region of Tho2, highlighting the importance of
      unfolded regions in eukaryotic proteins. Finally, we comment on THO recruitment
      to active chromatin, a role that is linked to mRNA biogenesis. 

PMID- 22964980
TI  - An unusual case of significant weight loss following malposition of a
      laparoscopic adjustable gastric band.
AB  - OBJECTIVE: Malposition or misplacement of gastric bands is a rare but recognised
      early complication of gastric band surgery. Malposition of the band would not
      normally result in significant weight loss after surgery. CASE REPORT: To our
      knowledge, we report the first case in the English literature of a malpositioned
      gastric band encircling the pericardial fat pad only, who presented with delayed
      symptoms of dysphagia and gastro-oesophageal reflux resulting in significant
      weight loss (>60% of excess body weight) approximately 6 years after primary
      surgery. The patient underwent a water-soluble contrast study with antero
      posterior views which was suggestive of a slipped band. However, on laparoscopy
      the band was found to be encircling the pericardial fat pad. CONCLUSION: We
      suggest that all contrast swallow studies for patients presenting with symptoms
      of gastric band slippage should include lateral views to exclude gastric band
      malposition, irrespective of the time of onset of symptoms after primary surgery.

PMID- 22964982
TI  - [The dialectic of success].

PMID- 22964981
TI  - The scaffolding protein IQGAP1 co-localizes with actin at the cytoplasmic face of
      the nuclear envelope: implications for cytoskeletal regulation.
AB  - IQGAP1 is an important cytoskeletal regulator, known to act at the plasma
      membrane to bundle and cap actin filaments, and to tether the cortical actin
      meshwork to microtubules via plus-end binding proteins. Here we describe the
      novel subcellular localization of IQGAP1 at the cytoplasmic face of the nuclear
      envelope, where it co-located with F-actin. The IQGAP1 and F-actin staining
      overlapped that of microtubules at the nuclear envelope, revealing a pattern
      strikingly similar to that observed at the plasma membrane. In detergent
      extracted cells IQGAP1 was retained at cytoskeletal structures at the nuclear
      envelope. This finding has new implications for involvement of IQGAP1 in cell
      polarization and migration events and potentially in cell cycle-associated
      nuclear envelope assembly/disassembly. 

PMID- 22964983
TI  - Utility of Maoto in an influenza season where reduced effectiveness of
      oseltamivir was observed - a clinical, non-randomized study in children.
AB  - BACKGROUND: In an influenza season where reduced effectiveness of oseltamivir was
      observed, we investigated the effectiveness of Maoto for influenza infection in
      children. METHODS: Patients diagnosed with influenza by rapid diagnostic kit
      underwent treatment in one of the following groups: Maoto-treated group (group 1
      (M)); oseltamivir-treated group (group 2 (O)); Maoto+oseltamivir-treated group
      (group 3 (M+O)); zanamivir-treated group (group 4 (Z)); and Maoto+zanamivir
      treated group (group 5 (M+Z)). RESULTS: In influenza A patients who completed the
      study (n = 150), the mean duration of fever after administration (DFA) was
      significantly shorter in group 3 (M+O) (31.1 h, p < 0.01) and in group 4 (Z)
      (35.2 h, p < 0.05), as compared to group 2 (O) (56.0 h). Among these, in patients
      aged <=5 years (n = 54), DFA was significantly shorter in group 1 (M) (33.2 h, p
      < 0.05) and in group 3 (M+O) (34.6 h, p < 0.05), as compared to group 2 (O) (61.4
      h). In influenza B patients who completed the study (n = 70), no significant
      differences in DFA were observed among the groups. CONCLUSION: Maoto may be
      useful, particularly in cases of influenza with low sensitivity to oseltamivir
      and in patients aged <=5 years for whom the use of zanamivir is difficult.

PMID- 22964984
TI  - Are the correct herbal claims by Hildegard von Bingen only lucky strikes? A new
      statistical approach.
AB  - BACKGROUND: Ancient and medieval herbal books are often believed to describe the
      same claims still in use today. Medieval herbal books, however, provide long
      lists of claims for each herb, most of which are not approved today, while the
      herb's modern use is often missing. So the hypothesis arises that a medieval
      author could have randomly hit on 'correct' claims among his many 'wrong' ones.
      METHODS: We developed a statistical procedure based on a simple probability
      model. We applied our procedure to the herbal books of Hildegard von Bingen (1098
      1179) as an example for its usefulness. Claim attributions for a certain herb
      were classified as 'correct' if approximately the same as indicated in actual
      monographs. RESULTS: The number of 'correct' claim attributions was significantly
      higher than it could have been by pure chance, even though the vast majority of
      Hildegard von Bingen's claims were not 'correct'. The hypothesis that Hildegard
      would have achieved her 'correct' claims purely by chance can be clearly
      rejected. CONCLUSION: The finding that medical claims provided by a medieval
      author are significantly related to modern herbal use supports the importance of
      traditional medicinal systems as an empirical source. However, since many
      traditional claims are not in accordance with modern applications, they should be
      used carefully and analyzed in a systematic, statistics-based manner. Our
      statistical approach can be used for further systematic comparison of herbal
      claims of traditional sources as well as in the fields of ethnobotany and
      ethnopharmacology.

PMID- 22964985
TI  - Preliminary data of a HAMD-17 validated symptom scale derived from the ICD-10 to
      diagnose depression in outpatients.
AB  - BACKGROUND: In outpatient settings diagnostic classification of depressive
      symptoms is mostly descriptive based on ICD-10. Depending on clinical experience
      and consultation time, diagnosis can be verified by validated scales. However,
      physicians working in primary care are familiar with ICD-10 criteria. Therefore,
      the aim of the present study was to examine the feasibility of the validation of
      an ICD-10-derived symptom scale for depression. METHODS: For this preliminary
      trial we generated a symptom scale derived 1:1 from the diagnostic criteria for
      depression given in the ICD-10 with 10 items. The Hamilton Rating Scale for
      Depression (HAMD-17) was used as reference in a population of 226 outpatients
      suffering from depressive symptoms. Correlation between scales as well as
      sensitivity and specificity of the ICD-10 scale were calculated. RESULTS: The
      generated ICD-10 symptom scale for depression could be analyzed in 219 patients
      and showed a significant and strong correlation with the HAMD-17 (p < 0.0001; rho
      = 0.75). The best tradeoffs between specificity and sensitivity of the ICD-10
      score were found at 10 points for the lower and 14 points for the upper cut-off.
      Overall sensitivity and specificity was 76.7 and 88.6%. Almost two thirds (i.e.
      65.3%) of the patients were correctly classified by the ICD-10 scale. CONCLUSION:
      The ICD-10 symptom scale examined in the current population was found to have
      fair correlation with the HAMD-17 as well as, in face of the limited variance of
      the patients' condition, acceptable sensitivity and specificity. Therefore, this
      preliminary study showed that the ICD-10-derived symptom scale seems appropriate
      to be investigated in a thorough validation trial.

PMID- 22964986
TI  - Acupuncture-induced pain relief and the human brain's default mode network - an
      extended view of central effects of acupuncture analgesia.
AB  - As a complementary medical procedure, acupuncture has a significant impact on the
      treatment of acute and chronic pain. Though the physiological mechanisms behind
      this method are still unclear, acupuncture has been claimed to rely also on
      changes in the central nervous system. Recent functional imaging studies indicate
      that the so-called default mode network (DMN) which consists of cortical midline
      structures and lateral parietal regions plays an important role in these
      processes. This brief overview describes the effects of analgesic acupuncture on
      the DMN architecture. The stronger interplay between systems dedicated to
      endogenous analgesia (periaqueductal gray), affective processing (anterior
      cingulate cortex, amygdala), memory (hippocampus), and self-projective thinking
      (DMN) following this therapy supports the notion that acupuncture is a mind-body
      therapy which helps to reintegrate important neural dimensions of inner life and
      to establish psychophysical pain homeostasis.

PMID- 22964987
TI  - [Development of lipoma following a single cupping massage - a case report].
AB  - BACKGROUND: The cupping massage is a form of bloodless cupping. This type of
      cupping is particularly used to treat muscular tension and musculoskeletal pain,
      such as chronic neck pain; however the data records on mechanisms and potential
      side effects are not satisfactory. CASE REPORT: In a study on the effectiveness
      of cupping massage in patients with chronic neck pain, one patient showed a
      formation of a lipoma in the cupping area after the first treatment session.
      CONCLUSION: Because of the short time interval between therapy and development of
      the lipoma, a primary cause is not realistic. This adverse event has not been
      described in the literature before, and the present report describes the case in
      summary.

PMID- 22964989
TI  - Cone structure in patients with usher syndrome type III and mutations in the
      Clarin 1 gene.
AB  - OBJECTIVE: To study macular structure and function in patients with Usher
      syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1).
      METHODS: High-resolution macular images were obtained by adaptive optics scanning
      laser ophthalmoscopy and spectral domain optical coherence tomography in 3
      patients with USH3 and were compared with those of age-similar control subjects.
      Vision function measures included best-corrected visual acuity, kinetic and
      static perimetry, and full-field electroretinography. Coding regions of the CLRN1
      gene were sequenced. RESULTS: CLRN1 mutations were present in all the patients; a
      20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and
      2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best
      corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3
      degrees  eccentricity. The inner segment-outer segment junction or the inner
      segment ellipsoid band was disrupted within 1 degrees  to 4 degrees  of the
      fovea, and the foveal inner and outer segment layers were significantly thinner
      than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and
      the preserved region ended abruptly. Retinal pigment epithelial cells were
      visible in patient 3 where cones were lost. CONCLUSIONS: Cones were observed
      centrally but not in regions with scotomas, and retinal pigment epithelial cells
      were visible in regions without cones in patients with CLRN1 mutations. High
      resolution measures of retinal structure demonstrate patterns of cone loss
      associated with CLRN1 mutations. CLINICAL RELEVANCE: These findings provide
      insight into the effect of CLRN1 mutations on macular cone structure, which has
      implications for the development of treatments for USH3. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00254605.

PMID- 22964990
TI  - How do microRNAs affect vascular smooth muscle cell biology?
AB  - PURPOSE OF REVIEW: Control of vascular smooth muscle cell (VSMC) phenotype is
      essential in the development and maintenance of a healthy vasculature.
      Acquisition of a synthetic, proproliferative phenotype by VSMCs following
      vascular insult is central to neointimal formation and the development of
      vascular pathology. MicroRNAs (miRNAs) are relatively recently discovered
      negative regulators of gene expression and act at the post-transcriptional level.
      MiRNAs have the potential to control VSMC phenotype. In this review, we discuss
      the recent findings on how miRNAs influence VSMC biology and acute vascular
      pathology. RECENT FINDINGS: MiRNAs play an important role in the gene regulation
      by growth factors and downstream transcription factors involved in VSMC
      phenotypic control and deregulation. Recent studies have revealed miRNAs that are
      involved in VSMC regulation and further identified several target genes which are
      implicated in VSMC pathobiology, highlighting new disease mechanisms. Paracrine
      miRNA-regulated crosstalk between endothelial and VSMCs has also been
      demonstrated, revealing a novel mechanism through which vascular cells
      communicate in health and disease. SUMMARY: MiRNAs appear to play a major role in
      the capability of VSMCs to phenotypically switch from a contractile to a
      synthetic state. Altering miRNA expression levels can prevent and even reverse
      the acquisition of VSMC synthetic phenotype in vivo and reduce neointimal
      formation, thereby implicating miRNAs as exciting future therapeutic targets for
      vascular proliferative disease.

PMID- 22964991
TI  - Role of colony-stimulating factors in atherosclerosis.
AB  - PURPOSE OF REVIEW: The varied effects of colony-stimulating factors (CSFs) on
      monocytes and macrophages during inflammation and atherosclerosis and its
      clinical presentation prompt the question whether the differing effects of CSFs
      dictate macrophage function and disease progression. RECENT FINDINGS: CSFs can
      give rise to heterogeneous populations of monocyte-derived macrophages that are
      characterized by disparate expression of distinct molecules which dictate their
      ability to process lipid and regulate inflammatory and immune responses. The CSFs
      have been found within atherosclerotic plaques and in the circulation where their
      levels may act as predictive biomarkers of disease progression. Accordingly,
      differing exposure to these factors imparts divergent genomic signatures and
      functional properties on macrophages and may impact the multifactorial steps
      involved in atherogenesis, plaque progression and instability. SUMMARY: Great
      interest in macrophage heterogeneity in the genesis and progression of
      atherosclerosis has led to the search for consistent markers of specific subsets
      in both animal models and humans. A better understanding of the overlap and
      competition between CSF regulation of macrophage phenotypes is therefore
      warranted, to allow their characterization in plaques. Subsequent targeted
      genetic and pharmacological intervention will facilitate the generation of
      therapeutic approaches to halt the progression and rupture of advanced
      atherosclerotic plaques.

PMID- 22964992
TI  - Macrophage proliferation and apoptosis in atherosclerosis.
AB  - PURPOSE OF REVIEW: Atherosclerosis is driven by cardiovascular risk factors that
      cause the recruitment of circulating immune cells beneath the vascular
      endothelium. Infiltrated monocytes differentiate into different macrophage
      subtypes with protective or pathogenic activities in vascular lesions. We discuss
      current knowledge about the molecular mechanisms that regulate lesional
      macrophage proliferation and apoptosis, two processes that occur during
      atherosclerosis development and regulate the number and function of macrophages
      within the atherosclerotic plaque. RECENT FINDINGS: Lesional macrophages in early
      phases of atherosclerosis limit disease progression by phagocytizing modified
      lipoproteins, cellular debris and dead cells that accumulate in the plaque.
      However, macrophages in advanced lesions contribute to a maladaptive,
      nonresolving inflammatory response that can lead to life-threatening acute
      thrombotic diseases (myocardial infarction or stroke). Macrophage-specific
      manipulation of genes involved in cell proliferation and apoptosis modulates
      lesional macrophage accumulation and atherosclerosis burden in mouse models, and
      studies are beginning to elucidate the underlying mechanisms. SUMMARY: Despite
      recent advances in our understanding of macrophage proliferation and apoptosis in
      atherosclerotic plaques, it remains unclear whether manipulating these processes
      will be beneficial or harmful. Advances in these areas may translate into more
      efficient therapies for the prevention and treatment of atherothrombosis.

PMID- 22964993
TI  - Endothelial mechanosensors of shear stress as regulators of atherogenesis.
AB  - PURPOSE OF REVIEW: Differences in local blood flow patterns along the endothelium
      may trigger abnormal vascular responses which can have profound
      pathophysiological consequences. While endothelial cells exposed to laminar blood
      flow (high shear stress) are protected from atherosclerosis formation, turbulent
      or disturbed blood flow, which occurs at bends and bifurcations of blood vessels,
      facilitates atherosclerosis formation. Here, we will highlight the endothelial
      cell mechanisms involved in detecting shear stress and their translation into
      downstream biochemical signals. RECENT FINDINGS: Prior evidence supports a role
      for integrins as mechanotransducers in the endothelium by promoting
      phosphorylation of different targets through the activation of focal adhesion
      kinase. Our recent findings show that integrins contact integrin-linked kinase
      and regulate vasomotor responses by an endothelial nitric oxide synthase
      dependent mechanism, which stabilizes the production of vasoactive factor nitric
      oxide. In addition, different structures of endothelial cells, mainly primary
      cilia, are investigated, as they can explain the differential responses to
      laminar versus disturbed flow. SUMMARY: The discovery of a connection between
      endothelial cell structures such as cilia, integrin, extracellular matrix, and
      signaling events opens today a new chapter in our understanding of the molecular
      mechanisms regulating vascular responses to the changes in flow.

PMID- 22964994
TI  - Electronegative low-density lipoprotein. A link between apolipoprotein B
      misfolding, lipoprotein aggregation and proteoglycan binding.
AB  - PURPOSE OF REVIEW: Subendothelial retention of lipoproteins is considered the
      first step in the development of atherosclerosis, but the molecular mechanisms
      involved are poorly understood. Recent findings on the atherogenic properties of
      a minor electronegative fraction of LDL (LDL(-)) could contribute to a better
      understanding of this process. RECENT FINDINGS: Circular dichroism, Trp
      fluorescence and two-dimensional nuclear magnetic resonance have shown that
      apolipoprotein B (apoB) in LDL(-) has an abnormal, misfolded conformation.
      Immunochemical analysis revealed a different conformation, mainly in the N
      terminal and C-terminal extremes. These alterations contribute to the high
      susceptibility to aggregation of LDL(-). Moreover, LDL(-) can seed the
      aggregation of native LDL, suggesting an amyloidogenic character that has been
      attributed to the amphipathic helix cluster in the alpha2-domain. A phospholipase
      C (PLC)-like activity associated to LDL(-) seems to play a major role in the LDL(
      )-induced aggregation. The aggregation of LDL(-) increases its binding to
      proteoglycans because of the abnormal conformation of the N-terminal extreme of
      apoB. SUMMARY: LDL(-) could play a relevant role in atherogenesis by acting as a
      priming factor that stimulates lipoprotein aggregation. This process, which
      appears to be mediated by a PLC-like activity intrinsic to LDL(-), increases the
      binding of LDL to proteoglycans and could promote subendothelial retention of
      these lipoproteins.

PMID- 22964995
TI  - Current world literature.

PMID- 22964996
TI  - Genetics and molecular biology:  the role of nucleotide oligomerization domain
      like genes in insulin resistance.

PMID- 22964997
TI  - Lipid metabolism.

PMID- 22964998
TI  - Atherosclerosis:  cell biology and lipoproteins.

PMID- 22964999
TI  - Inhibition of PCSK9:  is this the way forward for managing residual risk?

PMID- 22965001
TI  - Proton reduction to hydrogen in biological and chemical systems.
AB  - In the drive to devise catalytic systems to convert solar energy into the energy
      of chemical bonds, chemists and electrochemists are seeking inspiration from our
      understanding of enzymes involved in bioenergetics. This is particularly true for
      generating molecular hydrogen from high energy electrons derived from solar
      driven water splitting. In this case the natural enzymes are the [NiFe]- and
      [FeFe]-hydrogenases. In this article we review our present understanding of the
      structure and mechanistic functioning of these enzymes and how they are providing
      a blue print to the design and understanding of the mechanism of a variety of
      synthesized catalysts for proton reduction chemistry.

PMID- 22965002
TI  - Subjective and objective improvement in breathing after rhinoplasty.
AB  - OBJECTIVE: To determine whether rhinoplasty improves subjective and objective
      nasal patency. DESIGN: Retrospective study including subjective breathing scores
      and acoustic rhinometry before and 6 to 9 months after septorhinoplasty among a
      cohort of 31 patients. We used a paired t test to analyze the difference between
      preoperative and postoperative values. SETTING: Academic medical center.
      PATIENTS: Patients undergoing septorhinoplasty with potassium titanyl phosphate
      laser turbinate reduction at a single institution. RESULTS: The mean subjective
      breathing scores improved significantly, with an overall improvement of 38%. The
      overall mean volume increased and the overall resistance decreased, but the
      changes were significant only on the right side. The minimal cross-sectional area
      (MCA) did not change, but the distance of the MCA of the nasal cavity moved
      anteriorly by 0.23 cm on the left side. The patients were stratified into subsets
      based on other procedures undergone, including spreader grafts and alar batten
      grafts, and on the absence of osteotomies. These groups had similar results. In
      patients with severe obstruction, all measured values improved more than any
      other subgroup, including the MCA, which improved significantly by an average of
      55%. Patients with normal preoperative MCA values did not experience any
      significant changes except for an anterior shift in MCA. CONCLUSIONS:
      Septorhinoplasty increases nasal volume, decreases nasal resistance, and advances
      the MCA anteriorly. These changes coexist with subjective improvements in nasal
      patency, which suggests that this new anatomic configuration creates a positive
      outcome on nasal airflow. Spreader grafts do not increase the MCA significantly.
      Patients with preoperative severe obstruction have the best overall improvement,
      whether measured subjectively or objectively.

PMID- 22965003
TI  - Endoplasmic reticulum-derived multilamellar bodies in oocytes of mouse follicle
      cultures under oxidized low-density lipoprotein treatment.
AB  - OBJECTIVE: Multilamellar bodies associated with an organized endoplasmic
      reticulum (ER) arise in various somatic cell types, and a subtype called
      multivesicular bodies is described in oocytes. Both entities, so far undetermined
      in significance, may occur in oocytes of follicles under oxidative stress. In
      preovulatory follicles, oxidative stress appears to be caused by oxidized low
      density lipoprotein (ox-LDL). METHOD: Cultures of preantral mouse follicles were
      treated with 100 ug/ml ox-LDL or normal LDL (n-LDL) for 12-48 h or for 12 days
      during antral follicle growth followed by in vitro ovulation and harvest of
      cumulus oophorus complexes (COCs) with metaphase II (MII) oocytes on day 13.
      Preantral follicles, COCs, or MII oocytes were immunostained with anti-tubulin
      antibody or stained with actin-binding phalloidin for confocal microscopy.
      Ultrathin sections were prepared for electron microscopy. RESULTS: Preantral
      follicles exposed to n-LDL or ox-LDL developed normally, and MII oocytes in COCs
      possessed normal spindles with well-aligned chromosomes. In contrast, treated
      cumulus cells underwent apoptosis. Only the ox-LDL-treated preantral follicle
      oocytes showed ER-derived multilamellar bodies (EMBs) of type I, consisting of
      rough ER membranes for the envelope. The MII oocytes of COCs showed type II EMBs
      consisting of smooth/vesicular ER and were more prominent after ox-LDL than after
      n-LDL exposure. Degenerating mitochondria were prominent in oocytes of the ox-LDL
      group and judged as a sign of oxidative stress. CONCLUSION: Oxidative stress
      presumably induces damage of proteins and organelles in the oocytes. The EMBs
      might sequester the damaged structures for oocyte survival. Thus, EMBs could
      represent a novel form of autophagy.

PMID- 22965004
TI  - Relevance of the ACTN4 gene in African-Americans with non-diabetic end-stage
      renal disease.
AB  - BACKGROUND: African-Americans (AAs) are predisposed to non-diabetic (non-DM) end
      stage renal disease (ESRD), and studies have shown a genetic component to this
      risk. Rare mutations in ACTN4 (alpha-actinin-4), an actin-binding protein
      expressed in podocytes, cause familial focal segmental glomerulosclerosis.
      METHODS: We assessed the contribution of coding variants in ACTN4 to non-DM ESRD
      risk in AAs. Nineteen exons, 2,800 bases of the promoter and 392 bases of the 3'
      untranslated region of ACTN4 were sequenced in 96 AA non-DM ESRD cases and 96 non
      nephropathy controls (384 chromosomes). Sixty-seven single-nucleotide
      polymorphisms (SNPs) including 51 novel SNPs were identified. The SNPs comprised
      33 intronic, 21 promoter, 12 exonic, and one 3' variant. Sixty-two of the SNPs
      were genotyped in 296 AA non-DM ESRD cases and 358 non-nephropathy controls.
      RESULTS: One SNP, rs10404257, was associated with non-DM ESRD (p < 1.0E-4, odds
      ratio, OR = 0.76; confidence interval, CI = 0.59-0.98; additive model). Forty
      seven SNPs had minor allele frequencies <5%. These SNPs were segregated into risk
      and protective SNPs, and each category was collapsed into a single marker,
      designated by the presence or absence of any rare allele. The presence of any
      rare allele at a risk SNP was significantly associated with non-DM ESRD (p =
      0.001, dominant model). The SNPs with the strongest evidence for association (n =
      20) were genotyped in an independent set of 467 non-DM ESRD cases and 279
      controls. Although rs10404257 was not associated in this replication sample, when
      the samples were combined, rs10404257 was modestly associated (p = 0.032, OR =
      0.78, CI = 0.63-0.98; dominant model). SNPs were tested for interaction with
      markers in the APOL1 gene, previously associated with non-DM ESRD in AAs, and
      rs10404257 was modestly associated (p = 0.0261, additive model). CONCLUSIONS:
      This detailed evaluation of ACTN4 variation revealed limited evidence of
      association with non-DM ESRD in AAs.

PMID- 22965005
TI  - Report on the 10th EMBL conference on transcription and chromatin: August 25-28,
      2012 EMBL advanced training centre, Heidelberg, Germany.
AB  - Over 400 scientists from 38 countries gathered in the marvelous city of
      Heidelberg, Germany to attend the 10th EMBL Conference on Transcription and
      Chromatin. Surrounded by dark-green forest and overlooking a historic city, the
      charming environment of the EMBL as well as an all-star lineup of presenters
      attracted scientists from all over the world to discuss the latest findings and
      the future directions in the field. Superbly organized by Henk Stunnenberg,
      Eileen Furlong, Ali Shilatifard and Marc Timmers, the main topics of the
      conference included DNA, RNA and histone modifications, pluripotency and cellular
      reprogramming, transcriptional regulation, as well as chromatin dynamics and the
      effect of chromatin on gene regulation. In a pleasant summer climate that
      facilitated a stimulating and collaborative atmosphere, over 50 outstanding talks
      and more than 200 posters were presented. I apologize in advance to those
      speakers whose excellent work I have been unable to include in this report due to
      space constraints.

PMID- 22965007
TI  - Melanocortin 1 receptor (MC1R) variants in high melanoma risk patients are
      associated with specific dermoscopic ABCD features.
AB  - Individuals with two red hair colour (RHC)-MC1R genetic variants have light skin
      and blond/reddish hair and, in comparison with those without such alleles, are at
      an increased risk of developing melanoma. Our study investigated the association
      of RHC variants and the Total Dermo-scopy Score (TDS), and the items that make up
      the TDS, in those with atypical naevi and melanomas from high risk melanoma
      patients. Eight hundred and seventy-six atypical naevi and 21 melanomas were
      scored according to the TDS system and MC1R polymorphisms were determined.
      Analyses revealed that several TDS items including pigment network, dark-brown
      colour and streaks were more frequently observed in atypical naevi from
      individuals without RHC variants, while structureless areas were more often
      observed in individuals with two RHC variants. Finally, no significant difference
      in TDS was detected in atypical naevi from individuals with two RHC variants
      compared to those without RHC. Clinicians should be aware of a different
      dermoscopic naevus pheno-type in patients with light blond or RHC MC1R variants.

PMID- 22965006
TI  - Predicting the diagnosis of autism spectrum disorder using gene pathway analysis.
AB  - Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers
      to aid diagnosis. The current investigation interrogated single-nucleotide
      polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource
      Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and
      Genomes (KEGG)-derived pathways to identify affected cellular processes and
      develop a diagnostic test. This test was then applied to two independent samples
      from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust
      1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a
      Central European (CEU) cohort, we created a genetic diagnostic classifier
      consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in
      85.6% of CEU cases. This classifier also predicted 84.3% of cases in an
      ethnically related Tuscan cohort; however, prediction was less accurate (56.4%)
      in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes
      (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting
      as vulnerability SNPs, whereas others were protective. Prediction accuracy
      diminished as the number of SNPs analyzed in the model was decreased. Our
      diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7%
      in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets.
      In conclusion, we have developed an accurate diagnostic test for a genetically
      homogeneous group to aid in early detection of ASD. While SNPs differ across
      ethnic groups, our pathway approach identified cellular processes common to ASD
      across ethnicities. Our results have wide implications for detection,
      intervention and prevention of ASD. 

PMID- 22965008
TI  - Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone
      deacetylase inhibitors in combination with silibinin on non-small cell lung
      cancer cells.
AB  - There is a renewed focus on targeted therapy against epigenetic events that are
      altered during the pathogenesis of lung cancer. However, the use of epigenomic
      modifiers as monotherapy lacks efficacy; thus, there is a need to develop safe
      and effective drug combinatorial regimens, which reverse epigenetic modifications
      and exhibit profound anticancer activity. Based on these perspectives, we
      evaluated, for the first time, the efficacy and associated mechanisms of a novel
      combinatorial regimen of histone deacetylase inhibitors (HDACi)-trichostatin A
      (TSA) and suberoylanilide hydroxamic acid (SAHA)-with silibinin (a flavonolignan
      with established pre-clinical anti-lung cancer efficacy) against non-small cell
      lung cancer (NSCLC). Silibinin inhibited HDAC activity and decreased HDAC1-3
      levels in NSCLC cells, leading to an overall increase in global histone
      acetylation states of histones H3 and H4. Combinations of HDCAi with silibinin
      synergistically augmented the cytotoxic effects of these single agents, which was
      associated with a dramatic increase in p21 (Cdkn1a). Subsequent ChIP assay
      indicated increased acetylated histone H3 and H4 levels on p21 promoter region,
      resulting in its increased transcription. The enhanced p21 levels promoted
      proteasomal degradation of cyclin B1, the limited supply of which halts the
      progression of cells into mitosis. Indeed, the resultant biological effect was a
      significant G 2/M arrest by the combination treatment, followed by apoptotic cell
      death. Similar epigenetic modulations were observed in vivo, together with a
      marked reduction in xenograft growth. These findings are both novel and highly
      significant in establishing that HDACi with silibinin would be safe and effective
      to suppress NSCLC growth.

PMID- 22965009
TI  - Effectiveness of the computed analysis of electroglottographic signals in muscle
      tension dysphonia.
AB  - OBJECTIVE: To investigate the usefulness of electroglottography (EGG) parameters
      in the diagnosis and estimation of efficacy of voice therapy for muscle tension
      dysphonia (MTD). PATIENTS AND METHODS: Nineteen MTD participants, an equivalent
      number of dysphonic ('organic') patients with vocal fold lesions and as many
      normal speakers were enrolled. Acoustic (Ac) and EGG signals during sustained
      phonation were recorded simultaneously. The period and amplitude perturbation
      quotient of both signals, the closed quotient (CQ) of EGG signals (mean CQ) and
      its standard deviation (CQSD) were calculated, and subsequently compared among
      the three groups. These parameters in the MTD group were compared before and
      after voice therapy. RESULTS: The perturbation measures of both signals in the
      MTD group were either as high as or significantly higher than those in the
      organic group or the control group, respectively. Both the Ac and EGG parameters
      after therapy significantly decreased. The CQSD, but not mean CQ, also decreased
      after therapy. CONCLUSION: EGG parameters related to the regularity of vocal fold
      vibration, but not to the degree of vocal fold contact (mean CQ), are useful for
      the diagnosis and estimation of voice therapy outcome in MTD.

PMID- 22965010
TI  - Antifibrotic role of captopril after ureteral injury.
AB  - OBJECTIVES: To evaluate the antifibrotic role of captopril during ureteral
      scarring in a New Zealand rabbit model. MATERIALS AND METHODS: The tissue
      expression and the fluctuation of EGF, TGF-beta, FN, Col Ia1, Col Ia2 and Col III
      of the impaired ureter and the contralateral normal ureter were investigated by
      RT-PCR. The histological changes of the specimens were studied. When the
      sensitive markers had been selected, 10 New Zealand rabbits were randomly
      assigned to a captopril group and a control group. The specimens were harvested 2
      weeks after the injury and then the histological examination and RT-PCR were
      performed. RESULTS: By RT-PCR screening, EGF, TGF-beta, FN, Col Ia1 and Col Ia2
      were found to be significantly related to ureteral scarring (p < 0.05) confirmed
      by histological examination. The peak level of EGF, TGF-beta and Col Ia1 appeared
      at 2 weeks after the injury, while for Fn and Col Ia2 it was at 3 and 4 weeks
      after the injury. An obvious reduction of fibrotic scarring was observed in the
      captopril group. The expression of EGF, Fn and Col Ia2 in the captopril group was
      significantly lower than in the control group (p < 0.05) after the treatment.
      CONCLUSIONS: EGF, TGF-beta, Col Ia1, Col Ia2 and FN seemed to have an important
      role in the ureteral scarring after injury. Captopril might partially inhibit the
      fibrotic process by blocking the EGF, Col Ia2 and FN pathway so that it could be
      a promising treatment after ureteral injury.

PMID- 22965011
TI  - American Joint Committee on Cancer (AJCC) clinical classification predicts
      conjunctival melanoma outcomes.
AB  - PURPOSE: The aim of this study was to evaluate conjunctival melanoma outcomes
      based on American Joint Committee on Cancer classification. The study design
      constituted a nonrandomized interventional case series. METHODS: This was a
      retrospective chart review comprising 343 participants, and the main outcome
      measures were melanoma local recurrence, lymph node metastasis, distant
      metastasis, and death. RESULTS: On the basis of the American Joint Committee on
      Cancer classification (seventh edition), conjunctival melanoma was classified as
      T1 (196 [57%]), T2 (110 [32%]), T3 (37 [11%]), and T4 (0). The mean tumor basal
      diameter increased with tumor staging with 8.5 mm for T1, 12.7 mm for T2 (p =
      0.0003), and 16 mm for T3 (p < 0.0001). The melanoma arose from primary acquired
      melanosis (T1 = 71%; T2 = 84%; T3 = 81%), preexisting nevus (T1 = 8%; T2 = 5%; T3
      = 3%), or de novo (T1 = 21%; T2 = 12%; T3 = 16%). Outcomes at 5 years (Kaplan
      Meier) revealed melanoma local recurrence/new tumor in 44% T1, 78% T2 (p <
      0.0001), and 76% T3 (P=0.0044); regional lymph node metastasis in 17% T1, 52% T2
      (p < 0.0001), and 49% T3 (p = 0.0092); melanoma-related distant metastasis in 11%
      T1, 35% T2 (p < 0.0001), and 42% T3 (p = 0.0018); and melanoma-related death in
      5% T1, 20% T2 (p = 0.0655), and 23% T3 (p = 0.0526). Based on American Joint
      Committee on Cancer classification, factors predictive of melanoma recurrence
      included T2 stage (p < 0.0001), and T3 stage (p = 0.0061). After adjusting for
      tumor origin, factors predictive of regional lymph node metastasis, melanoma
      related distant metastasis, and melanoma-related death included melanoma arising
      de novo (p < 0.0001; p < 0.0001; p < 0.0001), T2 stage (p < 0.0001; p < 0.0001; p
      = 0.007), and T3 stage (p = 0.005; p = 0.0014; p = 0.0342). CONCLUSION: The
      American Joint Committee on Cancer staging predicts prognosis of conjunctival
      melanoma. Melanoma classified as T2 and T3 (compared with T1) showed
      significantly higher rates of local recurrence, regional lymph node metastasis,
      distant metastasis, and death.

PMID- 22965012
TI  - A histopathologic review of undiagnosed neoplasms in 205 evisceration specimens.
AB  - PURPOSE: Evisceration and enucleation are 2 ophthalmic surgeries used to treat
      blind and painful eyes. The benefits of evisceration over enucleation are many
      but this procedure is contraindicated in cases of a suspected intra-ocular mass.
      Given the lack of such studies in the literature, our aim was to review a large
      sample of eviscerated specimens to document the prevalence of unexpected
      neoplasms. METHODS: During the study period (1994-2011), 13,591 human ophthalmic
      specimens were received at the Henry C. Witelson Ophthalmic Pathology Laboratory
      and Registry. Of those, 205 were evisceration specimens. Histopathologic reports
      were reviewed to retrieve relevant clinical information that included clinical
      diagnosis, age, gender, laterality, and final histopathologic diagnosis. RESULTS:
      The total number of unexpected neoplasms was 4 (1.95%) including 2 (0.97%)
      malignancies: necrotic melanoma (1), ciliary body adenoma (1), iris nevus (1),
      and spindle cell melanoma (1). All the other remaining eyes had histopathologic
      findings that were consistent with the underlying diagnosis. CONCLUSIONS: With
      proper pre-operative evaluation, including history, ophthalmologic examination,
      and imaging studies, the rate of unexpected neoplasms in evisceration specimens
      were low. Evisceration is a simpler and cheaper procedure when compared with
      enucleation, and our results corroborate its safety, whenever indicated to treat
      blind and/or painful eyes.

PMID- 22965014
TI  - Making a malleable awl using a Steinmann pin for transnasal medial canthopexy.
AB  - PURPOSE: The authors designed a malleable awl using a Steinmann pin for
      transnasal medial canthopexy. METHODS: A Steinmann pin with a small eye at the
      end (00-0187-001-69, Zimmer Inc., Warsaw, IN, U.S.A.) was prepared, and its
      distal part was bent using pliers (01-9726, Walter Lorenz Surgical Inc.,
      Jacksonville, FL, U.S.A.) to make it a semicircle with the diameter of the circle
      being the intercanthal distance of the patient. RESULTS: Transnasal medial
      canthopexy was performed for 5 patients with telecanthus. All 5 patients had
      satisfactory results. CONCLUSIONS: This malleable awl might allow easy, safe, and
      stable fixation of the tendon, permit a safe approach with minimal bone
      fenestration, and be cost effective.

PMID- 22965013
TI  - Anterior filler displacement following injection of calcium hydroxylapatite gel
      (Radiesse) for anophthalmic orbital volume augmentation.
AB  - OBJECTIVE: To describe the complication of anterior filler displacement following
      injection of calcium hydroxylapatite gel (Radiesse) for anophthalmic enophthalmos
      correction. METHODS: Retrospective case series of patients who experienced
      anterior filler displacement following orbital injection of calcium
      hydroxylapatite. Data includes patient demographics, indication for injection,
      route and volume of injection, description of postinjection complications, and
      final outcome. RESULTS: Four cases of anterior filler displacement and expansion
      following injection of calcium hydroxylapatite were identified. The patients'
      ages ranged from 33 to 64 years old. All 4 patients underwent multiple prior
      orbital surgeries and suffered from anophthalmic enophthalmos. Injectable calcium
      hydroxylapatite was delivered transcutaneously, to the deep extraconal orbital
      space, via 27-gauge, 1.25-inch retrobulbar needles. Each patient received an
      initial 1.3 ml of filler, with 1 patient receiving an additional 0.8 ml. Within 1
      week, all patients experienced prominent, edematous lower eyelids. A CT scan of 1
      patient radiographically documented anterior migration of the filler material.
      Two patients required transconjunctival excision of the filler and infiltrated
      orbital fat. Histopathologic examination of 1 specimen revealed chronic foreign
      body granulomatous inflammation. Two patients were treated medically, with
      resolution of clinical findings over 6 to 9 months. CONCLUSIONS: Anterior filler
      displacement is a potential complication of orbital volume augmentation with
      injectable calcium hydroxylapatite. Patients should be counseled regarding this
      possibility when considering options for the treatment of anophthalmic
      enophthalmos. A history of multiple prior orbital surgeries, with associated
      tissue disruption and scarring, may be a risk factor for filler displacement.

PMID- 22965015
TI  - A modified levine palpebral spring for the treatment of myogenic ptosis.
AB  - PURPOSE: Surgical treatment of myogenic ptosis usually requires a form of
      frontalis suspension. Complications can include entropion, headache, contour
      abnormalities, and poor eyelid excursion. The Levine palpebral spring has been
      used successfully to augment eyelid closure in more than 2,000 patients. The
      authors present a modified Levine spring to correct ptosis in a patient with poor
      levator function. METHODS: Interventional case report. A 55-year-old man with
      profound myogenic ptosis was treated with bilateral modified Levine palpebral
      springs. Eyelid position, contour and excursion, blink reflex, lagophthalmos, and
      ocular surface were evaluated. RESULTS: The Levine palpebral spring functioned
      well to open both eyelids. Margin reflex distance improved from -3 mm to 3 m
      postoperatively. Excellent contour and excursion were observed. Orbicularis
      action, including blink reflex, was preserved, and ocular surface was not
      compromised. CONCLUSION: The modified Levine palpebral spring is an alternative
      to frontalis suspension in treating select patients with eyelid ptosis with poor
      levator function.

PMID- 22965016
TI  - The causative factors or characteristics of the Asian double eyelid: an anatomic
      study.
AB  - PURPOSE: To clarify the causative factor of Asian double eyelid. DESIGN:
      Experimental anatomic study. PARTICIPANTS: Twenty-six upper eyelids (13 right and
      13 left) from 17 Japanese cadavers (9 males and 8 females, mean age at death:
      73.1 years). METHODS: The specimens, obtained from the central part of the upper
      eyelids, were dehydrated, embedded in paraffin, cut into 7-MUm thick slices and
      stained with Masson trichrome. Statistical analysis was based on the Mann-Whitney
      U test. Statistical significance was defined as p < 0.05. MAIN OUTCOME MEASURES:
      Orbicularis oculi muscle thickness and shape, with or without the levator
      extension, orbicularis oculi muscle bundle spacing, thickness of upper eyelid
      skin and subcutaneous tissue, fusional site between the levator aponeurosis and
      the orbital septum, with or without inferior drooping of fat tissue. RESULTS: The
      orbicularis muscle was thinner at the skin crease of a double eyelid than at 10
      mm from the eyelid margin in the single eyelid group (p = 0.029). In 3 specimens
      the skin crease of double eyelid was at the tip of the bending orbicularis
      muscle, which was thick. Although the skin crease in the region of a double
      eyelid was thinner than in other parts of the skin, excluding the simple crease
      regions, other outcome measures were not shown as definite causative factors in
      creating the Asian double eyelid. CONCLUSIONS: The thickness of orbicularis oculi
      muscle or its bending shape, and the thickness of the skin at the skin crease,
      are major causative factors in Asian double eyelid formation.

PMID- 22965017
TI  - A case of secondary ankyloblepharon following bicanalicular silicone tube
      implantation.

PMID- 22965018
TI  - A pioneer in eyelid plastic, reconstructive, and esthetic surgery: Pietro
      Gradenigo.

PMID- 22965019
TI  - Re: "Subperiosteal abscess of the orbit: duration of intravenous antibiotic
      therapy in nonsurgical cases".

PMID- 22965021
TI  - Re: "Two cases of periocular cutaneous angiosarcoma".

PMID- 22965023
TI  - Nanoparticle-electrode impacts: the oxidation of copper nanoparticles has slow
      kinetics.
AB  - The electrochemical oxidation of copper nanoparticles in aqueous solution was
      studied via their electrolysis upon impacting a carbon electrode held at a
      suitable anodic potential. The oxidations were found to be quantitative such that
      complete oxidation of the particle took place allowing their sizing. Experiments
      were performed in 1.0 M HNO(3) and in 1.0 M HNO(3)-0.1 M KCl. In the former case
      a two electron oxidation to Cu(2+) was seen at a formal potential of +0.11 V (vs.
      SCE). In the latter case two separate one-electron oxidations at -0.01 V and
      +0.26 V were seen. In addition, theoretical results were derived for the analysis
      of impact-charge vs. potential data for reversible and irreversible charge
      transfer kinetics for nanoparticle oxidation. This enabled the inference that
      overpotential is required for the oxidations and Butler-Volmer transfer
      coefficients to be determined. The latter are compared with literature data seen
      for macroscopic copper.

PMID- 22965024
TI  - Protective autophagy induced by RBX1/ROC1 knockdown or CRL inactivation via
      modulating the DEPTOR-MTOR axis.
AB  - RBX1/ROC1 is an essential subunit of the largest multiunit Cullin-RING E3 ligase
      (CRL), which controls the degradation of diverse substrates, thereby regulating
      numerous cellular processes. Recently, we reported that RBX1 is overexpressed in
      hepatocellular carcinomas (HCC) and its expression is negatively correlated with
      patient survival. Moreover, siRNA silencing of RBX1 inhibits the proliferation of
      liver cancer cells both in vitro and in vivo by inducing CDKN1A/p21-dependent
      cell senescence. Interestingly, independent of senescence, RBX1 knockdown also
      triggers an autophagy response, due, at least in part, to the accumulation of the
      MTOR-inhibitory protein DEPTOR, a recently identified CRL substrate.
      Biologically, blockage of autophagy significantly enhances the growth-suppressive
      effect of RBX1 knockdown by triggering massive apoptosis, indicating that the
      autophagy response upon RBX1 knockdown serves as a survival signal in liver
      cells. Similar observations were also made in many types of human cancer cells
      upon inhibition of CRL by MLN4924. These findings suggest that RBX1-CRL is a
      promising anti-cancer drug target and provide proof-of-concept evidence for a
      novel drug combination of RBX1-CRL inhibitor and autophagy inhibitor for
      effective treatment of human cancer.

PMID- 22965025
TI  - Development and regeneration potential of the mammalian intervertebral disc.
AB  - At the present time, the normal cell proliferation rate and regeneration
      processes in the intervertebral disc (IVD) are not fully known. Historically, the
      IVD has been considered an organ with little or no regenerative capacity.
      However, several studies have identified the presence of cells expressing
      progenitor/stem cell markers in adult cartilage tissue and recent data suggest
      that adult mammalian IVDs have regenerative capacity, albeit slow. The aim of
      this review is to give an overview of the present knowledge regarding IVD
      development, regeneration and repair mechanisms in mammals, with a special focus
      on human discs. At a time when regenerative medicine is making progress and
      biological treatment options, such as stem cell therapy, are suggested for
      patients with degenerated discs causing chronic low back pain, basic knowledge
      about disc cells and their regenerative capacity form a useful basis for the
      exploration of new treatment options.

PMID- 22965026
TI  - Clinical practice guideline for the diagnosis and management of group A
      streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of
      America.
AB  - The guideline is intended for use by healthcare providers who care for adult and
      pediatric patients with group A streptococcal pharyngitis. The guideline updates
      the 2002 Infectious Diseases Society of America guideline and discusses diagnosis
      and management, and recommendations are provided regarding antibiotic choices and
      dosing. Penicillin or amoxicillin remain the treatments of choice, and
      recommendations are made for the penicillin-allergic patient, which now include
      clindamycin.

PMID- 22965027
TI  - Valley filtering in gapped graphene modulated by an antisymmetric magnetic field
      and an electric barrier.
AB  - We investigate valley-dependent electron transport properties of a gapped
      graphene film modulated by a ferromagnetic metal (FM) stripe with magnetization
      along the current direction. The antisymmetric stray field of the FM stripe alone
      does not generate a valley-polarized current due to an intrinsic symmetry. The
      inclusion of an electric barrier breaks this symmetry. It is shown that highly
      valley-polarized electron transport can be achieved in this magnetic-electric
      barrier structure, which results from a valley-dependent phase mechanism. The
      valley polarization can be tuned by the barrier parameters.

PMID- 22965028
TI  - Will the floodgates open for gene therapy?

PMID- 22965029
TI  - Further confirmation needed.

PMID- 22965030
TI  - First gene therapy nears landmark European market authorization.

PMID- 22965032
TI  - Regulatory fog lifts on obesity drugs.

PMID- 22965034
TI  - Industry cautiously welcomes Supreme Court decision on healthcare overhaul.

PMID- 22965036
TI  - Biotechs opt for alternative floatation strategy.

PMID- 22965039
TI  - GSK buys partner Human Genome Sciences.

PMID- 22965044
TI  - Drug pipeline: Q212.

PMID- 22965045
TI  - Patient power.

PMID- 22965046
TI  - How much risk are you prepared to take?

PMID- 22965047
TI  - To be or not to be transgenic.

PMID- 22965048
TI  - Broad consent in biobanking.

PMID- 22965049
TI  - An accelerated workflow for untargeted metabolomics using the METLIN database.

PMID- 22965050
TI  - Successful suppression of a field mosquito population by sustained release of
      engineered male mosquitoes.

PMID- 22965051
TI  - Teva v. AstraZeneca and secret prior art under 102(g)(2).

PMID- 22965053
TI  - Modulating WNT receptor turnover for tissue repair.

PMID- 22965054
TI  - RNA-mediated programmable DNA cleavage.

PMID- 22965055
TI  - Silicon dreams of cells into symbols.

PMID- 22965061
TI  - Navigating cancer network attractors for tumor-specific therapy.
AB  - Cells employ highly dynamic signaling networks to drive biological decision
      processes. Perturbations to these signaling networks may attract cells to new
      malignant signaling and phenotypic states, termed cancer network attractors, that
      result in cancer development. As different cancer cells reach these malignant
      states by accumulating different molecular alterations, uncovering these
      mechanisms represents a grand challenge in cancer biology. Addressing this
      challenge will require new systems-based strategies that capture the intrinsic
      properties of cancer signaling networks and provide deeper understanding of the
      processes by which genetic lesions perturb these networks and lead to disease
      phenotypes. Network biology will help circumvent fundamental obstacles in cancer
      treatment, such as drug resistance and metastasis, empowering personalized and
      tumor-specific cancer therapies.

PMID- 22965063
TI  - Theory to practice: real-world case-based learning for management degrees.

PMID- 22965062
TI  - Lessons from human teratomas to guide development of safe stem cell therapies.
AB  - The potential for the formation of teratomas or other neoplasms is a major safety
      roadblock to clinical application of pluripotent stem cell therapies. Preclinical
      assessment of the risk of tumor formation in this context poses considerable
      scientific and regulatory challenges, especially because animal xenograft models
      may not properly reflect the long-term tumorigenic potential of human cells. A
      better understanding of the biology of spontaneously occurring teratomas and
      related tumors in humans can help to guide efforts to assess and minimize the
      potential hazards of embryonic stem cell or induced pluripotent stem cell
      therapeutics. Here we review the features of teratomas derived experimentally
      from human pluripotent stem cells and argue that they most closely resemble
      spontaneous benign teratomas that occur early in both mouse and human life. The
      natural history and pathology of these spontaneously occurring teratomas provide
      important clues for preclinical safety assessment and patient monitoring in
      trials of stem cell therapies.

PMID- 22965067
TI  - Hyperglycemia suppresses cardiac stem cell homing to peri-infarcted myocardium
      via regulation of ERK1/2 and p38 MAPK activities.
AB  - Hyperglycemia in the acute phase of myocardial infarction (MI) is a marker of
      worse prognosis in both diabetic and non-diabetic patients; however, the role of
      hyperglycemia in the homing of cardiac stem cells (CSCs) to damaged myocardium
      post-MI and the possible mechanisms involved are not well understood. In this
      study, an MI model was induced in normoglycemic and hyperglycemic rats by left
      coronary artery ligation. Immunofluorescence was used to examine the migration of
      CSCs in vivo by injecting BrdU-labeled CSCs into the atrium-ventricle groove (AV
      groove). Immunohistochemistry, western blot analysis and ELISA were carried out
      to detect the expression of stem cell factor (SCF) protein and RT-PCR was
      conducted for the expression of SCF mRNA. Phosphorylation of ERK1/2 and p38 MAPK
      was detected by western blot analysis. Afterwards, cardiac function was evaluated
      by hemodynamic measurement. On Day 5 post-MI, the accumulation of CSCs
      significantly increased in the peri-infarcted myocardium in normoglycemic rats,
      which led to an improvement in cardiac function 3 weeks after MI. However, the
      accumulation of CSCs markedly decreased in hyperglycemic rats, followed by the
      decline of cardiac function. SCF expression, followed with phosphorylation of
      ERK1/2 and p38 MAPK, were also significantly downregulated in the peri-infarcted
      myocardium in hyperglycemic rats compared to normoglycemic rats. Moreover, SCF
      expression and the migration of CSCs were blocked by either the MEK-specific
      inhibitor PD98059 or the p38 MAPK-selective inhibitor SB203580. The experiments
      in vitro confirmed that hyperglycemia decreased SCF expression via reduction in
      ERK1/2 and p38 MAPK activities and further inhibited the migration of CSCs. The
      results suggest that hyperglycemia suppresses CSC migration towards the ischemic
      area post-MI. This is possibly due to decreased myocardial SCF expression via
      reduction of ERK1/2 and p38 MAPK activities in hyperglycemic rats.

PMID- 22965068
TI  - Standardization of a phonetic-phonological test for European-Portuguese children.
AB  - OBJECTIVE: To develop and standardize a phonetic-phonological test (Teste
      Fonetico-Fonologico-Avaliacao da Linguagem Pre-Escolar, TFF-ALPE) for the
      assessment of European-Portuguese (EP) children's articulation and phonological
      abilities. PATIENTS AND METHODS: In order to standardize TFF-ALPE, 768 children
      aged 3;0-6;11 participated in this study. The standardization, validity and
      reliability of TFF-ALPE were analyzed. RESULTS: TFF-ALPE presents strong cohesion
      and has strong inter- and intrajudge reliability. There was also a strong
      correlation between the TFF-ALPE data and those obtained in other studies. The
      content validity was demonstrated by the description of the test domain and the
      items that comprise TFF-ALPE. CONCLUSION: TFF-ALPE is a valid and reliable
      phonetic-phonological assessment instrument that speech-language pathologists can
      use with EP-speaking children.

PMID- 22965069
TI  - Preoperative hyponatremia: an opportunity for intervention?

PMID- 22965070
TI  - Synergistic effect of pasireotide and teriflunomide in carcinoids in vitro.
AB  - BACKGROUND/AIM: Somatostatin (SST) analogs are mainstay for controlling tumor
      proliferation and hormone secretion in carcinoid patients. Recent data suggest
      that extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation may
      potentiate the anti-tumor effects of SST analogs in carcinoids. Additionally,
      ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in
      carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic
      with SST analogs such as pasireotide (SOM230), which may be more effective than
      others in its class given its elevated receptor affinity and broader binding
      spectrum. Here, we investigate the effects of SOM230 in combination with
      teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. METHODS:
      Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a
      combination. Cell proliferation was measured using a rapid colorimetric assay.
      Western analysis was performed to analyze expression levels of achaete-scute
      complex-like 1 (ASCL1), chromogranin A (CgA), phosphorylated and total ERK1/2,
      and markers for apoptosis. RESULTS: Combination treatment with SOM230 and TFN
      reduced cell growth beyond the additive effect of either drug alone. Combination
      indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs
      as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA
      expression beyond the additive effect of either drug alone. Furthermore, it
      increased levels of phosphorylated ERK1/2, cleaved poly(ADP)-ribose polymerase
      and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated
      phosphorylated ERK1/2 expression following combination therapy may underlie the
      synergistic interaction between the two drugs. CONCLUSION: Since efficacy is
      achieved at lower doses, combination therapy may palliate symptoms at low
      toxicity levels. Because each drug has already been evaluated in clinical trials,
      combinatorial drug trials are warranted.

PMID- 22965071
TI  - CD40-CD40L: linking pancreatic, adipose tissue and vascular inflammation in type
      2 diabetes and its complications.
AB  - Numerous epidemiological studies have consistently demonstrated the strong
      association between type 2 diabetes mellitus (T2DM) and an increased risk to
      develop cardiovascular disease. The pathogenesis of T2DM and its complications
      are characterized by pancreatic, adipose tissue and vascular inflammation. CD40
      and CD40L, members of the tumour necrosis factor (receptor) TNF(R) family, are
      well known for their role in immunity and inflammation. Here we give an overview
      on the role of CD40-CD40L interactions in the pathogenesis of T2DM with a special
      focus on pancreatic, adipose tissue and vascular inflammation. In addition, we
      explore the role of soluble CD40L (sCD40L) as a potential biomarker for the
      development of cardiovascular disease in T2DM subjects. Finally, the therapeutic
      potential of CD40-CD40L inhibition in T2DM is highlighted.

PMID- 22965072
TI  - The single nucleotide polymorphisms in BRAP decrease the risk of metabolic
      syndrome in a Chinese young adult population.
AB  - The single nucleotide polymorphisms (SNPs) in the gene of breast cancer
      suppressor protein (BRCA1)-associated protein (BRAP) are significantly associated
      with coronary artery disease, but the molecular mechanisms are not understood. We
      examined the associations of the SNPs (rs11066001 and rs3782886) in BRAP with
      metabolic syndrome (MetS), which is a strong predictor of cardiovascular disease,
      and potential associations between these SNPs and factors related to
      inflammation. There were significant associations of both the SNPs with MetS
      [rs11066001, odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.96, p =
      0.028; rs3782886, OR 0.69, 95% CI 0.50-0.94, p = 0.020] under a dominant model
      after age and gender adjustment. Both SNPs were significantly associated with
      waist circumference, plasma glucose, glycated haemoglobin, triglycerides and
      nonesterified fatty acid. Our data provide evidence that the SNPs (rs11066001 and
      rs3782886) in BRAP decrease the risk of MetS, and associations of the SNPs with
      various components of MetS are different. Moreover, there are significant
      associations of both the SNPs with nonesterified fatty acid that could be
      involved in the inflammatory activity of electronegative low-density lipoprotein.

PMID- 22965074
TI  - Final state distributions of methyl radical desorption from ketone photooxidation
      on TiO2(110).
AB  - In this work, we report on product energy distributions for methyl radicals
      produced by UV photooxidation of a set of structurally related carbonyl
      molecules, R(CO)CH(3) (R = H, CH(3), C(2)H(5), C(6)H(5)), adsorbed on a
      TiO(2)(110) surface. Specifically, laser pump-probe techniques were used to
      measure the translational energy distributions of methyl radicals resulting from
      alpha-carbon bond cleavage induced by photoexcited charge carriers at the TiO(2)
      surface. Photoreaction requires the presence of co-adsorbed oxygen and/or
      background oxygen during UV laser (pump) exposure, which is consistent with the
      formation of a photoactive oxygen complex, i.e., eta(2)-bonded diolate species
      (R(COO)CH(3)). The methyl translational energy distributions were found to be
      bimodal for all molecules studied, with "slow" and "fast" dissociation channels.
      The "fast" methyl channel is attributed to prompt fragmentation of the diolate
      species following charge transfer at the TiO(2) surface. The average
      translational energies of the "fast" methyl channels are found to vary with R
      substituent and correlate with the mass of the remaining surface fragments,
      RCO(x) (x =1 or 2). By comparison, the average energies of the "slow" methyl
      channels do not show any obvious correlation with R-substituent. The apparent
      correlation of the "fast" methyl translation energies with surface fragment mass
      is consistent with a simple two-body fragmentation event isolated on the diolate
      molecule with little coupling to the surface. These results also suggest that the
      total available energy for methyl fragmentation does not vary significantly with
      changes in R-substituent and is representative of exit barriers leading to "fast"
      methyl fragments.

PMID- 22965073
TI  - Tumor necrosis factor receptors: biology and therapeutic potential in kidney
      diseases.
AB  - The major evolutionary advance represented in the human immune system is a
      mechanism of antigen-directed immunity in which tumor necrosis factor (TNF)-alpha
      and TNF receptors (TNFRs) play essential roles. Binding of TNF-alpha to the 55
      kDa type I TNFR (TNFR1, TNFRSF1A, CD120a, p55) or the 75-kDa type II TNFR (TNFR2,
      TNFRSF1B, CD120b, p75) activates signaling pathways controlling inflammatory,
      immune and stress responses, as well as host defense and apoptosis. Multiple
      studies have investigated the role of TNFRs in the development of early and late
      renal failure (diabetic nephropathy, nephroangiosclerosis, acute kidney
      transplant rejection, renal cell carcinoma, glomerulonephritis, sepsis and
      obstructive renal injury). This article reviews the general characteristics, the
      analytical aspects and the biology of TNFRs in this domain. In addition, the
      potential therapeutic application of specific TNFR blockers is discussed.

PMID- 22965075
TI  - Harvesting the potential of the human umbilical cord: isolation and
      characterisation of four cell types for tissue engineering applications.
AB  - The human umbilical cord (UC) has attracted interest as a source of cells for
      many research applications. UC solid tissues contain four cell types: epithelial,
      stromal, smooth muscle and endothelial cells. We have developed a unique protocol
      for the sequential extraction of all four cell types from a single UC, allowing
      tissue reconstruction using multiple cell types from the same source. By
      combining perfusion, immersion and explant techniques, all four cell types have
      been successfully expanded in monolayer cultures. We have also characterised
      epithelial and Wharton's jelly cells (WJC) by immunolabelling of specific
      proteins. Epithelial cell yields averaged at 2.3 * 10(5) cells per centimetre UC,
      and the cells expressed an unusual combination of keratins typical of simple,
      mucous and stratified epithelia. Stromal cells in the Wharton's jelly expressed
      desmin, alpha-smooth muscle actin, elastin, keratins (K12, K16, K18 and K19),
      vimentin and collagens. Expression patterns in cultured cells resembled those
      found in situ except for basement membrane components and type III collagen.
      These stromal cells featured a sustained proliferation rate up to passage 12
      after thawing. The mesenchymal stem cell (MSC) character of the WJC was confirmed
      by their expression of typical MSC surface markers and by adipogenic and
      osteogenic differentiation assays. To emphasise and demonstrate their potential
      for regenerative medicine, UC cell types were successfully used to produce human
      tissue-engineered constructs. Both bilayered stromal/epithelial and vascular
      substitutes were produced, establishing the versatility and importance of these
      cells for research and therapeutic applications.

PMID- 22965076
TI  - Complete genome sequence of Brucella abortus A13334, a new strain isolated from
      the fetal gastric fluid of dairy cattle.
AB  - Brucella abortus is a major pathogen that infects livestock and humans. A new
      strain of B. abortus (A13334) was isolated from the fetal gastric fluid of a
      dairy cow, with the aim of using it to compare genetic properties, analyze
      virulence factor, and survey the epidemiological relationship to other Brucella
      species. Here, we report the complete and annotated genome sequence of B. abortus
      A13334.

PMID- 22965077
TI  - Draft genome sequence of Fusobacterium nucleatum subsp. fusiforme ATCC 51190T.
AB  - Fusobacterium nucleatum, one of the major causative bacteria of periodontitis, is
      classified into five subspecies (nucleatum, polymorphum, vincentii, animalis, and
      fusiforme) on the basis of the several phenotypic characteristics and DNA
      homology. This is the first report of the draft genome sequence of F. nucleatum
      subsp. fusiforme ATCC 51190(T).

PMID- 22965078
TI  - Draft genome sequence of Yersinia pestis strain 2501, an isolate from the great
      gerbil plague focus in Xinjiang, China.
AB  - We deciphered the genome of Yersinia pestis strain 2501, isolated from the
      Junggar Basin, a newly discovered great gerbil plague focus in Xinjiang, China.
      The total length of assembly was 4,597,322 bp, and 4,265 coding sequences were
      predicted within the genome. It is the first Y. pestis genome from this plague
      focus.

PMID- 22965079
TI  - Draft genome sequence of Pseudomonas sp. strain Ag1, isolated from the midgut of
      the malaria mosquito Anopheles gambiae.
AB  - A Pseudomonas sp. bacterium was isolated from the midguts of Anopheles gambiae
      mosquitoes. Here we present the annotated Pseudomonas sp. draft genome sequence
      as a contribution to the efforts of characterization of the mosquito gut
      microbiome.

PMID- 22965080
TI  - Genomic insights into the emerging human pathogen Mycobacterium massiliense.
AB  - Mycobacterium massiliense (Mycobacterium abscessus group) is an emerging pathogen
      causing pulmonary disease and skin and soft tissue infections. We report the
      genome sequence of the type strain CCUG 48898.

PMID- 22965081
TI  - Genome sequence of Brucella melitensis S66, an isolate of sequence type 8,
      prevalent in China.
AB  - Brucella melitensis is the most-represented Brucella species causing human
      brucellosis in China. Here we report the complete genome sequence of B.
      melitensis strain S66, a representative strain of sequence type 8 (ST8), which is
      prevalent in China, making it possible to compare the genome sequences of
      isolates from different countries.

PMID- 22965082
TI  - Draft genome sequence of Moritella dasanensis strain ArB 0140, a psychrophilic
      bacterium isolated from the Arctic Ocean.
AB  - The psychrophilic bacterium Moritella dasanensis strain ArB 0140 was isolated
      near a glacier in Kongsfjorden, Svalbard Archipelago, Norway. Here we report a
      4.89-Mb draft genome sequence of Moritella dasanensis ArB 0140, which could
      provide comprehensive information on a psychrophilic mechanism in extreme
      environments.

PMID- 22965083
TI  - Complete genome sequence of Klebsiella oxytoca E718, a New Delhi metallo-beta
      lactamase-1-producing nosocomial strain.
AB  - We report the complete genome sequence of Klebsiella oxytoca E718, a New Delhi
      metallo-beta-lactamase-1 (NDM-1)-producing strain isolated from a renal
      transplant patient. The genome contains a 6,097,032-bp chromosome and two
      multidrug resistance plasmids with sizes of 324,906 bp and 110,781 bp.

PMID- 22965084
TI  - Complete genome sequence of Mycobacterium massiliense.
AB  - Mycobacterium massiliense is a rapidly growing bacterium associated with
      opportunistic infections. The genome of a representative isolate (strain GO 06)
      recovered from wound samples from patients who underwent arthroscopic or
      laparoscopic surgery was sequenced. To the best of our knowledge, this is the
      first announcement of the complete genome sequence of an M. massiliense strain.

PMID- 22965085
TI  - Draft genome sequence of Pelosinus fermentans JBW45, isolated during in situ
      stimulation for Cr(VI) reduction.
AB  - Pelosinus fermentans JBW45 is an anaerobic, lactate-fermenting bacterium isolated
      from Cr(VI)-contaminated groundwater at the Hanford Nuclear Reservation 100-H
      site (Washington) that was collected after stimulation with a polylactate
      compound. The genome sequence of this organism will provide insight into the
      metabolic potential of a predominant population during stimulation for metal
      reducing conditions.

PMID- 22965086
TI  - Complete genome sequence of Mycoplasma wenyonii strain Massachusetts.
AB  - Mycoplasma wenyonii is a hemotrophic mycoplasma that causes acute and chronic
      infections in cattle. Here, we announce the first complete genome sequence of
      this organism. The genome is a single circular chromosome with 650,228 bp and
      G+C% of 33.9. Analyses of M. wenyonii genome will provide insights into its
      biology.

PMID- 22965087
TI  - Draft genome sequence of Lactobacillus rossiae DSM 15814(T).
AB  - The draft genome sequence of Lactobacillus rossiae DSM 15814(T) (CS1, ATCC BAA
      88) was determined by a whole-genome shotgun approach. Reads were assembled to a
      2.9-Mb draft version. RAST genome annotation evidenced 2,723 predicted coding
      sequences. Many carbohydrate, amino acid, and amino acid derivative subsystem
      features were found.

PMID- 22965088
TI  - Draft genome sequence of Flavobacterium sp. strain F52, isolated from the
      rhizosphere of bell pepper (Capsicum annuum L. cv. Maccabi).
AB  - Here we report the draft genome sequence of Flavobacterium sp. strain F52,
      isolated from the rhizosphere of bell pepper (Capsicum annuum L. cv. Maccabi).
      Flavobacterium spp. are ubiquitous in the rhizospheres of agricultural crops;
      however, little is known about their physiology. To our knowledge, this is the
      first published genome of a root-associated Flavobacterium strain.

PMID- 22965089
TI  - Draft genome sequence of Citreicella aestuarii strain 357, a member of the
      Roseobacter clade isolated without xenobiotic pressure from a petroleum-polluted
      beach.
AB  - Citreicella aestuarii 357 is a member of the Roseobacter clade that was isolated
      without xenobiotic pressure from an oil-polluted sand sample from the Galician
      coast (Spain). Its genome sequence suggests an organoheterotrophic metabolism,
      including a wide catabolic potential for aromatic hydrocarbons.

PMID- 22965090
TI  - Complete genome sequence of Streptococcus pyogenes M1 476, isolated from a
      patient with streptococcal toxic shock syndrome.
AB  - Here, we report the completely annotated genome sequence of Streptococcus
      pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome
      (STSS) during pregnancy. The genome sequence will provide new insights into the
      mechanisms underlying STSS.

PMID- 22965091
TI  - Genome sequence of the plant growth-promoting rhizobacterium Bacillus sp. strain
      916.
AB  - Bacillus sp. strain 916, isolated from the soil, showed strong activity against
      Rhizoctonia solani. Here, we present the high-quality draft genome sequence of
      Bacillus sp. strain 916. Its 3.9-Mb genome reveals a number of genes whose
      products are possibly involved in promotion of plant growth or antibiosis.

PMID- 22965092
TI  - Genome sequence of Enterobacter radicincitans DSM16656(T), a plant growth
      promoting endophyte.
AB  - Enterobacter radicincitans sp. nov. DSM16656(T) represents a new species of the
      genus Enterobacter which is a biological nitrogen-fixing endophytic bacterium
      with growth-promoting effects on a variety of crop and model plant species. The
      presence of genes for nitrogen fixation, phosphorous mobilization, and
      phytohormone production reflects this microbe's potential plant growth-promoting
      activity.

PMID- 22965093
TI  - Draft genome sequence of butanol-acetone-producing Clostridium beijerinckii
      strain G117.
AB  - A recently discovered wild-type strain, Clostridium beijerinckii G117, is unique
      in producing butanol and acetone but negligible amounts of ethanol, unlike
      previously identified acetone-butanol-ethanol (ABE)-generating microbes. Here we
      report the draft genome sequence of strain G117 (5,806,675 bp; GC content, 29.7%)
      and the novel findings obtained from its genome annotations.

PMID- 22965094
TI  - Genome sequence of Streptomyces auratus strain AGR0001, a phoslactomycin
      producing actinomycete.
AB  - Streptomyces auratus strain AGR0001 produces neophoslactomycin A, a novel analog
      of phoslactomycin that possesses potent activity against some phytopathogenic
      fungi. Here, the draft genome sequence of S. auratus strain AGR0001 is presented,
      which would provide insight into the biosynthetic mechanism of neophoslactomycin
      A.

PMID- 22965095
TI  - Draft genome sequence of the marine Streptomyces sp. strain AA1529, isolated from
      the Yellow Sea.
AB  - Here we report the draft genome sequence of a Streptomyces strain, AA1529,
      isolated from marine sediment from the Yellow Sea. Its genome contains a subset
      of unique genes and gene clusters that encode diverse secondary metabolites,
      suggesting great potential as a source for the discovery of novel gene clusters
      and bioactive compounds.

PMID- 22965096
TI  - Genome sequence of pectin-degrading Alishewanella aestuarii strain B11(T),
      isolated from tidal flat sediment.
AB  - We present the genome sequence of Alishewanella aestuarii B11(T) (=KCTC
      22051(T)=DSM 19476(T)). This species, isolated from tidal flat sediment, was
      reported to be a novel species. A. aestuarii is known to degrade pectin, an
      important component of plant cell wall. The presence of the genes related to
      pectin metabolism in this strain indicates its capability to utilize pectin.

PMID- 22965097
TI  - Genome sequence of Pseudomonas stutzeri strain JM300 (DSM 10701), a soil isolate
      and model organism for natural transformation.
AB  - Pseudomonas stutzeri strain JM300 (DSM 10701) is a denitrifying soil isolate and
      a model organism for natural transformation in bacteria. Here we report the first
      complete genome sequence of JM300, the reference strain of genomovar 8 for the
      species.

PMID- 22965098
TI  - Genome sequence of the rice pathogen Pseudomonas fuscovaginae CB98818.
AB  - Pseudomonas fuscovaginae is a phytopathogenic bacterium causing bacterial sheath
      brown rot of cereal crops. Here, we present the draft genome sequence of P.
      fuscovaginae CB98818, originally isolated from a diseased rice plant in China.
      The draft genome will aid in epidemiological studies, comparative genomics, and
      quarantine of this broad-host-range pathogen.

PMID- 22965099
TI  - Draft genome sequences of Enterobacter sp. isolate Ag1 from the midgut of the
      malaria mosquito Anopheles gambiae.
AB  - An isolate of Enterobacter sp. was obtained from the microbial community within
      the gut of the Anopheles gambiae mosquito, a major malaria vector in Africa. This
      genome was sequenced and annotated. The genome sequences will facilitate
      subsequent efforts to characterize the mosquito gut microbiome.

PMID- 22965100
TI  - Draft genome sequence of Tsukamurella sp. strain 1534.
AB  - A draft genome sequence of Tsukamurella sp., an aerobic bacterium isolated from a
      human sputum specimen, is described here. A new virus or provirus, TPA4, was
      characterized.

PMID- 22965101
TI  - Genome sequence of the thermostable-agarase-producing marine bacterium
      Catenovulum agarivorans YM01(T), which reveals the presence of a series of
      agarase-encoding genes.
AB  - Marine bacterium Catenovulum agarivorans YM01(T) can produce highly thermostable
      agarases. The draft genome of YM01(T) is about 5.36 Mb and harbors approximately
      4,913 genes, including 15 agarase (2 alpha-agarase and 13 beta-agarase)-encoding
      genes, which will provide references to functional characterization of various
      agarases from marine bacteria.

PMID- 22965102
TI  - Genome sequence of Citrobacter sp. strain A1, a dye-degrading bacterium.
AB  - Citrobacter sp. strain A1, isolated from a sewage oxidation pond, is a
      facultative aerobe and mesophilic dye-degrading bacterium. This organism degrades
      azo dyes efficiently via azo reduction and desulfonation, followed by the
      successive biotransformation of dye intermediates under an aerobic environment.
      Here we report the draft genome sequence of Citrobacter sp. A1.

PMID- 22965103
TI  - Complete genome sequence of the hydrogenotrophic, methanogenic archaeon
      Methanoculleus bourgensis strain MS2(T), Isolated from a sewage sludge digester.
AB  - Methanoculleus bourgensis, of the order Methanomicrobiales, is a dominant
      methanogenic archaeon in many biogas-producing reactor systems fed with renewable
      primary products. It is capable of synthesizing methane via the hydrogenotrophic
      pathway utilizing hydrogen and carbon dioxide or formate as the substrates. Here
      we report the complete and finished genome sequence of M. bourgensis strain
      MS2(T), isolated from a sewage sludge digester.

PMID- 22965104
TI  - Genome sequences of Brucella melitensis 16M and its two derivatives 16M1w and
      16M13w, which evolved in vivo.
AB  - Brucella melitensis is an intracellular pathogen that induces chronic infection
      in humans. Here, we report the genome sequences of 16M and its two derivatives,
      16M1w and 16M13w, which were allowed to adapt in vivo for 1 and 13 weeks,
      respectively. Our findings contribute to the investigation of adaptive mutations
      and mechanisms of chronic infection by B. melitensis.

PMID- 22965105
TI  - Complete genome sequence of the porcine isolate Enterococcus faecalis D32.
AB  - The complete and annotated genome sequence of Enterococcus faecalis D32, a
      commensal strain isolated from a Danish pig, suggests putative adaptation to the
      porcine host and absence of distinct virulence-associated traits.

PMID- 22965106
TI  - Whole-genome shotgun sequence of Rhodococcus species strain JVH1.
AB  - Here we present a whole-genome shotgun sequence of Rhodococcus species strain
      JVH1, an organism capable of degrading a variety of organosulfur compounds. In
      particular, JVH1 is able to selectively cleave carbon-sulfur bonds within alkyl
      chains. A large number of oxygenases were identified, consistent with other
      members of the genus.

PMID- 22965107
TI  - Phase II PARAMOUNT trial of LCZ696.

PMID- 22965108
TI  - Comparison of prasugrel and clopidogrel in the setting of ACS without
      revascularization.

PMID- 22965109
TI  - Intra-aortic balloon support for MI and cardiogenic shock--time to change the
      guidelines?

PMID- 22965110
TI  - Identifying silent heart disease.

PMID- 22965111
TI  - FFR-guided revascularization versus medical therapy-the debate goes on.

PMID- 22965113
TI  - Cardiovascular diseases after the Great East Japan Earthquake.

PMID- 22965112
TI  - CLARIFYing the differences between men and women with stable CAD.

PMID- 22965114
TI  - Visible-light-driven photocatalytic carbon-doped porous ZnO nanoarchitectures for
      solar water-splitting.
AB  - C-doped ZnO hierarchically porous nanoarchitectures were synthesized in situ on
      indium tin oxide (ITO) through a counter strategy. The PEC performance of the C
      doped ZnO nanoarchitectures in the splitting of water without sacrificial
      reagents was systematically evaluated for the first time. In comparison to other
      ZnO-based photoanodes in the literature, C-doped ZnO nanoarchitectures exhibit a
      striking photoresponse. Not only do they have a maximum IPCE value of 95%, but
      they also have an IPCE at the monochromatic wavelength of 400 nm as high as
      26.6%, implying that modification by doping with carbon substantially improves
      the light utilization and conversion efficiency in the visible region of interest
      over those obtained using a conventional ZnO structure. This model hybrid
      photoanode will enable us to design high-activity, high-stability visible-light
      driven photoelectrodes in the future.

PMID- 22965115
TI  - Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks.
AB  - NF-E2-related factor 2 (Nrf2) is a key transcription factor that is critical for
      cellular defense against oxidative and xenobiotic insults. Nrf2 heterodimerizes
      with small Maf (sMaf) proteins and binds to antioxidant response elements (AREs)
      to activate a battery of cytoprotective genes. However, it remains unclear to
      what extent the Nrf2-sMaf heterodimers contribute to ARE-dependent gene
      regulation on a genome-wide scale. We performed chromatin immunoprecipitation
      coupled with high-throughput sequencing and identified the binding sites of Nrf2
      and MafG throughout the genome. Compared to sites occupied by Nrf2 alone, many
      sites co-occupied by Nrf2 and MafG exhibit high enrichment and are located in
      species-conserved genomic regions. The ARE motifs were significantly enriched
      among the recovered Nrf2-MafG-binding sites but not among the Nrf2-binding sites
      that did not display MafG binding. The majority of the Nrf2-regulated
      cytoprotective genes were found in the vicinity of Nrf2-MafG-binding sites.
      Additionally, sequences that regulate glucose metabolism and several amino acid
      transporters were identified as Nrf2-MafG target genes, suggesting diverse roles
      for the Nrf2-MafG heterodimer in stress response. These data clearly support the
      notion that Nrf2-sMaf heterodimers are complexes that regulate batteries of genes
      involved in various aspects of cytoprotective and metabolic functions through
      associated AREs.

PMID- 22965116
TI  - Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.
AB  - Piwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in
      transposon silencing in the male germline of fetal and newborn mice. Both are
      also present in adult testes; however, their function here remains a mystery.
      Here, we confirm that most piRNAs in meiotic spermatocytes originate from
      clusters in non-repeat intergenic regions of DNA. The regulation of these piRNA
      clusters, including the processing of the precursor transcripts into individual
      piRNAs, is accomplished through mostly unknown processes. We present a possible
      regulatory mechanism for one such cluster, named cluster 1082B, located on
      chromosome 7 in the mouse genome. The 1082B precursor transcript and its 788
      unique piRNAs are repressed by the Alkbh1 dioxygenase and the testis-specific
      transcription repressor Tzfp. We observe a remarkable >1000-fold upregulation of
      individual piRNAs in pachytene spermatocytes isolated from Alkbh1- and Tzfp
      deficient murine testes. Repression of cluster 1082B is further supported by the
      identification of a 10-bp Tzfp recognition sequence contained within the
      precursor transcript. Downregulation of LINE1 and IAP transcripts in the Alkbh1-
      and Tzfp-deficient mice leads us to propose a potential role for the 1082B
      encoded piRNAs in transposon control.

PMID- 22965117
TI  - Structural mechanism of Staphylococcus aureus Hfq binding to an RNA A-tract.
AB  - Hfq is a post-transcriptional regulator that plays a key role in bacterial gene
      expression by binding AU-rich sequences and A-tracts to facilitate the annealing
      of sRNAs to target mRNAs and to affect RNA stability. To understand how Hfq from
      the Gram-positive bacterium Staphylococcus aureus (Sa) binds A-tract RNA, we
      determined the crystal structure of an Sa Hfq-adenine oligoribonucleotide
      complex. The structure reveals a bipartite RNA-binding motif on the distal face
      that is composed of a purine nucleotide-specificity site (R-site) and a non
      discriminating linker site (L-site). The (R-L)-binding motif, which is also
      utilized by Bacillus subtilis Hfq to bind (AG)(3)A, differs from the (A-R-N)
      tripartite poly(A) RNA-binding motif of Escherichia coli Hfq whereby the Sa Hfq R
      site strongly prefers adenosine, is more aromatic and permits deeper insertion of
      the adenine ring. R-site adenine-stacking residue Phe30, which is conserved among
      Gram-positive bacterial Hfqs, and an altered conformation about beta3 and beta4
      eliminate the adenosine-specificity site (A-site) and create the L-site. Binding
      studies show that Sa Hfq binds (AU)(3)A ~ (AG)(3)A >= (AC)(3)A > (AA)(3)A and L
      site residue Lys33 plays a significant role. The (R-L) motif is likely utilized
      by Hfqs from most Gram-positive bacteria to bind alternating (A-N)(n) RNA.

PMID- 22965119
TI  - The architecture of eukaryotic translation.
AB  - Translation in baker's yeast involves the coordinated interaction of 200,000
      ribosomes, 3,000,000 tRNAs and between 15,000 and 60,000 mRNAs. It is currently
      unknown whether this specific constellation of components has particular
      relevance for the requirements of the yeast proteome, or whether this is simply a
      frozen accident. Our study uses a computational simulation model of the genome
      wide translational apparatus of yeast to explore quantitatively which
      combinations of mRNAs, ribosomes and tRNAs can produce viable proteomes.
      Surprisingly, we find that if we only consider total translational activity over
      time without regard to composition of the proteome, then there are many and
      widely differing combinations that can generate equivalent synthesis yields. In
      contrast, translational activity required for generating specific proteomes can
      only be achieved within a much more constrained parameter space. Furthermore, we
      find that strongly ribosome limited regimes are optimal for cells in that they
      are resource efficient and simplify the dynamics of the system.

PMID- 22965118
TI  - Solitary restriction endonucleases in prokaryotic genomes.
AB  - Prokaryotic restriction-modification (R-M) systems defend the host cell from the
      invasion of a foreign DNA. They comprise two enzymatic activities: specific DNA
      cleavage activity and DNA methylation activity preventing cleavage. Typically,
      these activities are provided by two separate enzymes: a DNA methyltransferase
      (MTase) and a restriction endonuclease (RE). In the absence of a corresponding
      MTase, an RE of Type II R-M system is highly toxic for the cell. Genes of the R-M
      system are linked in the genome in the vast majority of annotated cases. There
      are only a few reported cases in which the genes of MTase and RE from one R-M
      system are not linked. Nevertheless, a few hundreds solitary RE genes are present
      in the Restriction Enzyme Database (http://rebase.neb.com) annotations. Using the
      comparative genomic approach, we analysed 272 solitary RE genes. For 57 solitary
      RE genes we predicted corresponding MTase genes located distantly in a genome. Of
      the 272 solitary RE genes, 99 are likely to be fragments of RE genes. Various
      explanations for the existence of the remaining 116 solitary RE genes are also
      discussed.

PMID- 22965120
TI  - Massive gene acquisitions in Mycobacterium indicus pranii provide a perspective
      on mycobacterial evolution.
AB  - Understanding the evolutionary and genomic mechanisms responsible for turning the
      soil-derived saprophytic mycobacteria into lethal intracellular pathogens is a
      critical step towards the development of strategies for the control of
      mycobacterial diseases. In this context, Mycobacterium indicus pranii (MIP) is of
      specific interest because of its unique immunological and evolutionary
      significance. Evolutionarily, it is the progenitor of opportunistic pathogens
      belonging to M. avium complex and is endowed with features that place it between
      saprophytic and pathogenic species. Herein, we have sequenced the complete MIP
      genome to understand its unique life style, basis of immunomodulation and habitat
      diversification in mycobacteria. As a case of massive gene acquisitions, 50.5% of
      MIP open reading frames (ORFs) are laterally acquired. We show, for the first
      time for Mycobacterium, that MIP genome has mosaic architecture. These gene
      acquisitions have led to the enrichment of selected gene families critical to MIP
      physiology. Comparative genomic analysis indicates a higher antigenic potential
      of MIP imparting it a unique ability for immunomodulation. Besides, it also
      suggests an important role of genomic fluidity in habitat diversification within
      mycobacteria and provides a unique view of evolutionary divergence and putative
      bottlenecks that might have eventually led to intracellular survival and
      pathogenic attributes in mycobacteria.

PMID- 22965121
TI  - An archaeal sRNA targeting cis- and trans-encoded mRNAs via two distinct domains.
AB  - We report on the characterization and target analysis of the small (s)RNA(162) in
      the methanoarchaeon Methanosarcina mazei. Using a combination of genetic
      approaches, transcriptome analysis and computational predictions, the bicistronic
      MM2441-MM2440 mRNA encoding the transcription factor MM2441 and a protein of
      unknown function was identified as a potential target of this sRNA, which due to
      processing accumulates as three stabile 5' fragments in late exponential growth.
      Mobility shift assays using various mutants verified that the non-structured
      single-stranded linker region of sRNA(162) (SLR) base-pairs with the MM2440
      MM2441 mRNA internally, thereby masking the predicted ribosome binding site of
      MM2441. This most likely leads to translational repression of the second cistron
      resulting in dis-coordinated operon expression. Analysis of mutant RNAs in vivo
      confirmed that the SLR of sRNA(162) is crucial for target interactions.
      Furthermore, our results indicate that sRNA(162)-controlled MM2441 is involved in
      regulating the metabolic switch between the carbon sources methanol and
      methylamine. Moreover, biochemical studies demonstrated that the 5' end of
      sRNA(162) targets the 5'-untranslated region of the cis-encoded MM2442 mRNA.
      Overall, this first study of archaeal sRNA/mRNA-target interactions unraveled
      that sRNA(162) acts as an antisense (as)RNA on cis- and trans-encoded mRNAs via
      two distinct domains, indicating that cis-encoded asRNAs can have larger target
      regulons than previously anticipated.

PMID- 22965122
TI  - Oligomerization and DNA binding of Ler, a master regulator of pathogenicity of
      enterohemorrhagic and enteropathogenic Escherichia coli.
AB  - Ler is a DNA-binding, oligomerizable protein that regulates pathogenicity islands
      in enterohemorrhagic and enteropathogenic Escherichia coli strains. Ler
      counteracts the transcriptional silencing effect of H-NS, another oligomerizable
      nucleoid-associated protein. We studied the oligomerization of Ler in the absence
      and presence of DNA by atomic force microscopy. Ler forms compact particles with
      a multimodal size distribution corresponding to multiples of 3-5 units of Ler.
      DNA wraps around Ler particles that contain more than 15-16 Ler monomers. The
      resulting shortening of the DNA contour length is in agreement with previous
      measurements of the length of DNA protected by Ler in footprinting assays. We
      propose that the repetition unit corresponds to the number of monomers per turn
      of a tight helical Ler oligomer. While the repressor (H-NS) and anti-repressor
      (Ler) have similar DNA-binding domains, their oligomerization domains are
      unrelated. We suggest that the different oligomerization behavior of the two
      proteins explains the opposite results of their interaction with the same or
      proximal regions of DNA.

PMID- 22965123
TI  - FadE: whole genome methylation analysis for multiple sequencing platforms.
AB  - DNA methylation plays a central role in genomic regulation and disease. Sodium
      bisulfite treatment (SBT) causes unmethylated cytosines to be sequenced as
      thymine, which allows methylation levels to reflected in the number of 'C'-'C'
      alignments covering reference cytosines. Di-base color reads produced by
      lifetech's SOLiD sequencer provide unreliable results when translated to bases
      because single sequencing errors effect the downstream sequence. We describe
      FadE, an algorithm to accurately determine genome-wide methylation rates directly
      in color or nucleotide space. FadE uses SBT unmethylated and untreated data to
      determine background error rates and incorporate them into a model which uses
      Newton-Raphson optimization to estimate the methylation rate and provide a
      credible interval describing its distribution at every reference cytosine. We
      sequenced two slides of human fibroblast cell-line bisulfite-converted fragment
      library with the SOLiD sequencer to investigate genome-wide methylation levels.
      FadE reported widespread differences in methylation levels across CpG islands and
      a large number of differentially methylated regions adjacent to genes which
      compares favorably to the results of an investigation on the same cell-line using
      nucleotide-space reads at higher coverage levels, suggesting that FadE is an
      accurate method to estimate genome-wide methylation with color or nucleotide
      reads. http://code.google.com/p/fade/.

PMID- 22965124
TI  - A comprehensive comparison of RNA-Seq-based transcriptome analysis from reads to
      differential gene expression and cross-comparison with microarrays: a case study
      in Saccharomyces cerevisiae.
AB  - RNA-seq, has recently become an attractive method of choice in the studies of
      transcriptomes, promising several advantages compared with microarrays. In this
      study, we sought to assess the contribution of the different analytical steps
      involved in the analysis of RNA-seq data generated with the Illumina platform,
      and to perform a cross-platform comparison based on the results obtained through
      Affymetrix microarray. As a case study for our work we, used the Saccharomyces
      cerevisiae strain CEN.PK 113-7D, grown under two different conditions (batch and
      chemostat). Here, we asses the influence of genetic variation on the estimation
      of gene expression level using three different aligners for read-mapping (Gsnap,
      Stampy and TopHat) on S288c genome, the capabilities of five different
      statistical methods to detect differential gene expression (baySeq, Cuffdiff,
      DESeq, edgeR and NOISeq) and we explored the consistency between RNA-seq analysis
      using reference genome and de novo assembly approach. High reproducibility among
      biological replicates (correlation>=0.99) and high consistency between the two
      platforms for analysis of gene expression levels (correlation>=0.91) are
      reported. The results from differential gene expression identification derived
      from the different statistical methods, as well as their integrated analysis
      results based on gene ontology annotation are in good agreement. Overall, our
      study provides a useful and comprehensive comparison between the two platforms
      (RNA-seq and microrrays) for gene expression analysis and addresses the
      contribution of the different steps involved in the analysis of RNA-seq data.

PMID- 22965125
TI  - A dual switch controls bacterial enhancer-dependent transcription.
AB  - Bacterial RNA polymerases (RNAPs) are targets for antibiotics. Myxopyronin binds
      to the RNAP switch regions to block structural rearrangements needed for
      formation of open promoter complexes. Bacterial RNAPs containing the major
      variant sigma(54) factor are activated by enhancer-binding proteins (bEBPs) and
      transcribe genes whose products are needed in pathogenicity and stress responses.
      We show that (i) enhancer-dependent RNAPs help Escherichia coli to survive in the
      presence of myxopyronin, (ii) enhancer-dependent RNAPs partially resist
      inhibition by myxopyronin and (iii) ATP hydrolysis catalysed by bEBPs is
      obligatory for functional interaction of the RNAP switch regions with the
      transcription start site. We demonstrate that enhancer-dependent promoters
      contain two barriers to full DNA opening, allowing tight regulation of
      transcription initiation. bEBPs engage in a dual switch to (i) allow propagation
      of nucleated DNA melting from an upstream DNA fork junction and (ii) complete the
      formation of the transcription bubble and downstream DNA fork junction at the RNA
      synthesis start site, resulting in switch region-dependent RNAP clamp closure and
      open promoter complex formation.

PMID- 22965126
TI  - Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes
      from prion-infected neuronal cells.
AB  - Prion diseases are transmissible neurodegenerative disorders affecting both
      humans and animals. The cellular prion protein, PrP(C), and the abnormal
      infectious form, PrP(Sc), are found associated with exosomes, which are small 50
      130 nm vesicles released from cells. Exosomes also contain microRNAs (miRNAs), a
      class of non-coding RNA, and have been utilized to identify miRNA signatures for
      diagnosis of disease. While some miRNAs are deregulated in prion-infected brain
      tissue, the role of miRNA in circulating exosomes released during prion disease
      is unknown. Here, we investigated the miRNA profile in exosomes released from
      prion-infected neuronal cells. We performed the first small RNA deep sequencing
      study of exosomes and demonstrated that neuronal exosomes contain a diverse range
      of RNA species including retroviral RNA repeat regions, messenger RNA fragments,
      transfer RNA fragments, non-coding RNA, small nuclear RNA, small nucleolar RNA,
      small cytoplasmic RNA, silencing RNA as well as known and novel candidate miRNA.
      Significantly, we show that exosomes released by prion-infected neuronal cells
      have increased let-7b, let-7i, miR-128a, miR-21, miR-222, miR-29b, miR-342-3p and
      miR-424 levels with decreased miR-146 a levels compared to non-infected exosomes.
      Overall, these results demonstrate that circulating exosomes released during
      prion infection have a distinct miRNA signature that can be utilized for
      diagnosis and understanding pathogenic mechanisms in prion disease.

PMID- 22965127
TI  - Base-pairing preferences, physicochemical properties and mutational behaviour of
      the DNA lesion 8-nitroguanine.
AB  - 8-Nitro-2'-deoxyguanosine (8-nitrodG) is a relatively unstable, mutagenic lesion
      of DNA that is increasingly believed to be associated with tissue inflammation.
      Due to the lability of the glycosidic bond, 8-nitrodG cannot be incorporated into
      oligodeoxynucleotides (ODNs) by chemical DNA synthesis and thus very little is
      known about its physicochemical properties and base-pairing preferences. Here we
      describe the synthesis of 8-nitro-2'-O-methylguanosine, a ribonucleoside analogue
      of this lesion, which is sufficiently stable to be incorporated into ODNs.
      Physicochemical studies demonstrated that 8-nitro-2'-O-methylguanosine adopts a
      syn conformation about the glycosidic bond; thermal melting studies and molecular
      modelling suggest a relatively stable syn-8-nitroG.anti-G base pair.
      Interestingly, when this lesion analogue was placed in a primer-template system,
      extension of the primer by either avian myeloblastosis virus reverse
      transcriptase (AMV-RT) or human DNA polymerase beta (pol beta), was significantly
      impaired, but where incorporation opposite 8-nitroguanine did occur, pol beta
      showed a 2:1 preference to insert dA over dC, while AMV-RT incorporated
      predominantly dC. The fact that no 8-nitroG.G base pairing is seen in the primer
      extension products suggests that the polymerases may discriminate against this
      pairing system on the basis of its poor geometric match to a Watson-Crick pair.

PMID- 22965128
TI  - The THO complex cooperates with the nuclear RNA surveillance machinery to control
      small nucleolar RNA expression.
AB  - THO is a multi-protein complex that promotes coupling between transcription and
      mRNA processing. In contrast to its role in mRNA biogenesis, we show here that
      the fission yeast THO complex negatively controls the expression of non-coding
      small nucleolar (sno) RNAs. Accordingly, the deletion of genes encoding subunits
      of the evolutionarily conserved THO complex results in increased levels of mature
      snoRNAs. We also show physical and functional connections between THO and
      components of the TRAMP polyadenylation complex, whose loss of function also
      results in snoRNA accumulation. Consistent with a role in snoRNA expression, we
      demonstrate that THO and TRAMP complexes are recruited to snoRNA genes, and that
      a functional THO complex is required to maintain TRAMP occupancy at sites of
      snoRNA transcription. Our findings suggest that THO promotes exosome-mediated
      degradation of snoRNA precursors by ensuring the presence of the TRAMP complex at
      snoRNA genes. This study unveils an unexpected role for THO in the control of
      snoRNA expression and provides a new link between transcription and nuclear RNA
      decay.

PMID- 22965130
TI  - The Ighmbp2 helicase structure reveals the molecular basis for disease-causing
      mutations in DMSA1.
AB  - Mutations in immunoglobulin u-binding protein 2 (Ighmbp2) cause distal spinal
      muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is
      clinically characterized by distal limb weakness and respiratory distress.
      However, despite extensive studies, the mechanism of disease-causing mutations
      remains elusive. Here we report the crystal structures of the Ighmbp2 helicase
      core with and without bound RNA. The structures show that the overall fold of
      Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense
      mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large
      conformational changes in response to RNA binding, rotating 30 degrees  and 10
      degrees , respectively. The RNA binding and ATPase activities of Ighmbp2 are
      further enhanced by the R3H domain, located just downstream of the helicase core.
      Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure
      provides a molecular basis for understanding the disease-causing consequences of
      Ighmbp2 mutations.

PMID- 22965129
TI  - Regulation of the nucleosome unwrapping rate controls DNA accessibility.
AB  - Eukaryotic genomes are repetitively wrapped into nucleosomes that then regulate
      access of transcription and DNA repair complexes to DNA. The mechanisms that
      regulate extrinsic protein interactions within nucleosomes are unresolved. We
      demonstrate that modulation of the nucleosome unwrapping rate regulates protein
      binding within nucleosomes. Histone H3 acetyl-lysine 56 [H3(K56ac)] and DNA
      sequence within the nucleosome entry-exit region additively influence nucleosomal
      DNA accessibility by increasing the unwrapping rate without impacting rewrapping.
      These combined epigenetic and genetic factors influence transcription factor (TF)
      occupancy within the nucleosome by at least one order of magnitude and enhance
      nucleosome disassembly by the DNA mismatch repair complex, hMSH2-hMSH6. Our
      results combined with the observation that ~30% of Saccharomyces cerevisiae TF
      binding sites reside in the nucleosome entry-exit region suggest that modulation
      of nucleosome unwrapping is a mechanism for regulating transcription and DNA
      repair.

PMID- 22965131
TI  - From next-generation sequencing alignments to accurate comparison and validation
      of single-nucleotide variants: the pibase software.
AB  - Scientists working with single-nucleotide variants (SNVs), inferred by next
      generation sequencing software, often need further information regarding true
      variants, artifacts and sequence coverage gaps. In clinical diagnostics, e.g.
      SNVs must usually be validated by visual inspection or several independent SNV
      callers. We here demonstrate that 0.5-60% of relevant SNVs might not be detected
      due to coverage gaps, or might be misidentified. Even low error rates can
      overwhelm the true biological signal, especially in clinical diagnostics, in
      research comparing healthy with affected cells, in archaeogenetic dating or in
      forensics. For these reasons, we have developed a package called pibase, which is
      applicable to diploid and haploid genome, exome or targeted enrichment data.
      pibase extracts details on nucleotides from alignment files at user-specified
      coordinates and identifies reproducible genotypes, if present. In test cases
      pibase identifies genotypes at 99.98% specificity, 10-fold better than other
      tools. pibase also provides pair-wise comparisons between healthy and affected
      cells using nucleotide signals (10-fold more accurately than a genotype-based
      approach, as we show in our case study of monozygotic twins). This comparison
      tool also solves the problem of detecting allelic imbalance within heterozygous
      SNVs in copy number variation loci, or in heterogeneous tumor sequences.

PMID- 22965132
TI  - Common chaperone activity in the G-domain of trGTPase protects L11-L12
      interaction on the ribosome.
AB  - Translational GTPases (trGTPases) regulate all phases of protein synthesis. An
      early event in the interaction of a trGTPase with the ribosome is the contact of
      the G-domain with the C-terminal domain (CTD) of ribosomal protein L12 (L12-CTD)
      and subsequently interacts with the N-terminal domain of L11 (L11-NTD). However,
      the structural and functional relationships between L12-CTD and L11-NTD remain
      unclear. Here, we performed mutagenesis, biochemical and structural studies to
      identify the interactions between L11-NTD and L12-CTD. Mutagenesis of conserved
      residues in the interaction site revealed their role in the docking of trGTPases.
      During docking, loop62 of L11-NTD protrudes into a cleft in L12-CTD, leading to
      an open conformation of this domain and exposure of hydrophobic core. This
      unfavorable situation for L12-CTD stability is resolved by a chaperone-like
      activity of the contacting G-domain. Our results suggest that all trGTPases
      regardless of their different specific functions-use a common mechanism for
      stabilizing the L11-NTD*L12-CTD interactions.

PMID- 22965133
TI  - RhesusBase: a knowledgebase for the monkey research community.
AB  - Although the rhesus macaque is a unique model for the translational study of
      human diseases, currently its use in biomedical research is still in its infant
      stage due to error-prone gene structures and limited annotations. Here, we
      present RhesusBase for the monkey research community (http://www.rhesusbase.org).
      We performed strand-specific RNA-Seq studies in 10 macaque tissues and generated
      1.2 billion 90-bp paired-end reads, covering >97.4% of the putative exon in
      macaque transcripts annotated by Ensembl. We found that at least 28.7% of the
      macaque transcripts were previously mis-annotated, mainly due to incorrect exon
      intron boundaries, incomplete untranslated regions (UTRs) and missed exons.
      Compared with the previous gene models, the revised transcripts show clearer
      sequence motifs near splicing junctions and the end of UTRs, as well as cleaner
      patterns of exon-intron distribution for expression tags and cross-species
      conservation scores. Strikingly, 1292 exon-intron boundary revisions between
      coding exons corrected the previously mis-annotated open reading frames. The
      revised gene models were experimentally verified in randomly selected cases. We
      further integrated functional genomics annotations from >60 categories of public
      and in-house resources and developed an online accessible database. User-friendly
      interfaces were developed to update, retrieve, visualize and download the
      RhesusBase meta-data, providing a 'one-stop' resource for the monkey research
      community.

PMID- 22965135
TI  - A hybrid G-quadruplex structure formed between RNA and DNA explains the
      extraordinary stability of the mitochondrial R-loop.
AB  - In human mitochondria the transcription machinery generates the RNA primers
      needed for initiation of DNA replication. A critical feature of the leading
      strand origin of mitochondrial DNA replication is a CG-rich element denoted
      conserved sequence block II (CSB II). During transcription of CSB II, a G
      quadruplex structure forms in the nascent RNA, which stimulates transcription
      termination and primer formation. Previous studies have shown that the newly
      synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near
      the leading-strand origin of DNA replication. We here demonstrate that the
      unusual behavior of the RNA primer is explained by the formation of a stable G
      quadruplex structure, involving the CSB II region in both the nascent RNA and the
      non-template DNA strand. Based on our data, we suggest that G-quadruplex
      formation between nascent RNA and the non-template DNA strand may be a regulated
      event, which decides the fate of RNA primers and ultimately the rate of
      initiation of DNA synthesis in human mitochondria.

PMID- 22965134
TI  - Novel insights from hybrid LacI/GalR proteins: family-wide functional attributes
      and biologically significant variation in transcription repression.
AB  - LacI/GalR transcription regulators have extensive, non-conserved interfaces
      between their regulatory domains and the 18 amino acids that serve as 'linkers'
      to their DNA-binding domains. These non-conserved interfaces might contribute to
      functional differences between paralogs. Previously, two chimeras created by
      domain recombination displayed novel functional properties. Here, we present a
      synthetic protein family, which was created by joining the LacI DNA-binding
      domain/linker to seven additional regulatory domains. Despite 'mismatched'
      interfaces, chimeras maintained allosteric response to their cognate effectors.
      Therefore, allostery in many LacI/GalR proteins does not require interfaces with
      precisely matched interactions. Nevertheless, the chimeric interfaces were not
      silent to mutagenesis, and preliminary comparisons suggest that the chimeras
      provide an ideal context for systematically exploring functional contributions of
      non-conserved positions. DNA looping experiments revealed higher order (dimer
      dimer) oligomerization in several chimeras, which might be possible for the
      natural paralogs. Finally, the biological significance of repression differences
      was determined by measuring bacterial growth rates on lactose minimal media.
      Unexpectedly, moderate and strong repressors showed an apparent induction phase,
      even though inducers were not provided; therefore, an unknown mechanism might
      contribute to regulation of the lac operon. Nevertheless, altered growth
      correlated with altered repression, which indicates that observed functional
      modifications are significant.

PMID- 22965136
TI  - Sensitive and selective amplification of methylated DNA sequences using helper
      dependent chain reaction in combination with a methylation-dependent restriction
      enzymes.
AB  - We have developed a novel technique for specific amplification of rare methylated
      DNA fragments in a high background of unmethylated sequences that avoids the need
      of bisulphite conversion. The methylation-dependent restriction enzyme GlaI is
      used to selectively cut methylated DNA. Then targeted fragments are tagged using
      specially designed 'helper' oligonucleotides that are also used to maintain
      selection in subsequent amplification cycles in a process called 'helper
      dependent chain reaction'. The process uses disabled primers called 'drivers'
      that can only prime on each cycle if the helpers recognize specific sequences
      within the target amplicon. In this way, selection for the sequence of interest
      is maintained throughout the amplification, preventing amplification of unwanted
      sequences. Here we show how the method can be applied to methylated Septin 9, a
      promising biomarker for early diagnosis of colorectal cancer. The GlaI digestion
      and subsequent amplification can all be done in a single tube. A detection
      sensitivity of 0.1% methylated DNA in a background of unmethylated DNA was
      achieved, which was similar to the well-established Heavy Methyl method that
      requires bisulphite-treated DNA.

PMID- 22965137
TI  - Periprocedural management of the patient with diabetes mellitus undergoing
      coronary angiography: current practice.

PMID- 22965138
TI  - Extravasation of intravesical chemotherapy for non-muscle-invasive bladder
      cancer.
AB  - PURPOSE: To report our experience with symptomatic extravasation of intravesical
      chemotherapy administered within 24 h after transurethral resection (TUR) over
      the past 10 years. METHODS: We identified all consecutive patients who presented
      with symptomatic extravasation of intravesical chemotherapy following TUR between
      2001 and 2011. We assessed the severity of the postoperative complications using
      the modified Clavien system. RESULTS: We identified 9 patients (mean age 59,
      range 40-76 years) with symptomatic extravasation. One patient had grade II, 2
      had grade IIIa, and 5 patients had grade IIIb complications according to the
      Clavien system. Surgery was needed in 6 of 9 patients. One required ICU
      management (Clavien IV). No patients died in the postoperative course.
      CONCLUSION: Extravasation can cause severe complications and diagnosis is often
      protracted. Considering the growing practice of immediate intravesical
      instillations, the number of patients with symptomatic extravasation is expected
      to rise. An increased awareness of this possible complication is warranted.

PMID- 22965140
TI  - The combination of mycophenolate mofetil with corticosteroids induces remission
      of Henoch-Schonlein purpura nephritis.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is a form of systemic vasculitis that
      can progress to Henoch-Schonlein purpura nephritis (HSPN), and the most effective
      treatment remains controversial. Our aim was to compare the effects of oral
      mycophenolate mofetil (MMF) with low-dose prednisone and the full-dose
      corticosteroids (CS; prednisone) for the induction therapy of HSPN with large
      proteinuria. METHODS: Fifty-three patients with biopsy-proved HSPN with large
      proteinuria (>2.0 g/24 h) were divided into two groups: the MMF group (n = 27)
      who received oral MMF 1.0 g/day (1.5 g/day for patients with a body weight >70
      kg) combined with low-dose prednisone (0.4-0.5 mg/kg/day), and the CS group (n =
      26) who received the full-dose prednisone (0.8-1.0 mg/kg/day). We compared the
      effects of inducing remission at 6-month follow-up and the overall remission rate
      at the end of the follow-up between the two groups. RESULTS: At 6 months, the
      estimated glomerular filtration rate level remained stable, while the urine
      protein decreased significantly in both groups, and the remission rate was 76.9%
      in the CS group and 55.5% in the MMF group (p = 0.101). With a median follow-up
      of 28.8 months in the CS group and 28.2 months in the MMF group, the overall
      remission rate was 80.8% in the CS group and 77.8% in the MMF group (p = 0.788).
      The MMF group had less side effects than the CS group (48.1 vs. 76.9%, p =
      0.031). The relapse was 4/21 (19.0%) in the CS group and 0/21 in the MMF group (p
      = 0.115). CONCLUSION: MMF is useful for inducing remission and maintaining
      remission in Chinese HSPN, and may be used as a steroid-sparing agent in the
      treatment of HSPN.

PMID- 22965141
TI  - Evaluation of changes in the tumor microenvironment after sorafenib therapy by
      sequential histology and 18F-fluoromisonidazole hypoxia imaging in renal cell
      carcinoma.
AB  - The mechanistic dissociation of 'tumor starvation' versus 'vascular
      normalization' following anti-angiogenic therapy is a subject of intense
      controversy in the field of experimental research. In addition, accurately
      evaluating changes of the tumor microenvironment after anti-angiogenic therapy is
      important for optimizing treatment strategy. Sorafenib has considerable anti
      angiogenic effects that lead to tumor starvation and induce tumor hypoxia in the
      highly vascularized renal cell carcinoma (RCC) xenografts. 18F-fluoromisonidazole
      (18F-FMISO) is a proven hypoxia imaging probe. Thus, to clarify early changes in
      the tumor microenvironment following anti-angiogenic therapy and whether 18F
      FMISO imaging can detect those changes, we evaluated early changes in the tumor
      microenvironment after sorafenib treatment in an RCC xenograft by sequential
      histological analysis and 18F-FMISO autoradiography (ARG). A human RCC xenograft
      (A498) was established in nude mice, for histological studies and ARG, and
      further assigned to the control and sorafenib-treated groups (80 mg/kg, per os).
      Mice were sacrificed on Days 1, 2, 3 and 7 in the histological study, and on Days
      3 and 7 in ARG after sorafenib treatment. Tumor volume was measured every day.
      18F-FMISO and pimonidazole were injected intravenously 4 and 2 h before
      sacrifice, respectively. Tumor sections were stained with hematoxylin and eosin
      and immunohistochemically with pimonidazole and CD31. Intratumoral 18F-FMISO
      distribution was quantified in ARG. Tumor volume did not significantly change on
      Day 7 after sorafenib treatment. In the histological study, hypoxic fraction
      significantly increased on Day 2, mean vessel density significantly decreased on
      Day 1 and necrosis area significantly increased on Day 2 after sorafenib
      treatment. Intratumoral 18F-FMISO distribution significantly increased on Days 3
      (10.2-fold, p<0.01) and 7 (4.1-fold, p<0.01) after sorafenib treatment. The
      sequential histological evaluation of the tumor microenvironment clarified tumor
      starvation in A498 xenografts treated with sorafenib. 18F-FMISO hypoxia imaging
      confirmed the tumor starvation. 18F-FMISO PET may contribute to determine an
      optimum treatment protocol after anti-angiogenic therapy.

PMID- 22965142
TI  - Alzheimer disease: a tale of two prions.
AB  - Alzheimer disease (AD) has traditionally been thought to involve the misfolding
      and aggregation of two different factors that contribute in parallel to
      pathogenesis: amyloid-beta (Abeta) peptides, which represent proteolytic
      fragments of the transmembrane amyloid precursor protein, and tau, which normally
      functions as a neuronally enriched, microtubule-associated protein that
      predominantly accumulates in axons. Recent evidence has challenged this model,
      however, by revealing numerous functional interactions between Abeta and tau in
      the context of pathogenic mechanisms for AD. Moreover, the propagation of toxic,
      misfolded Abeta and tau bears a striking resemblance to the propagation of toxic,
      misfolded forms of the canonical prion protein, PrP, and misfolded Abeta has been
      shown to induce tau misfolding in vitro through direct, intermolecular
      interaction. In this review we discuss evidence for the prion-like properties of
      both Abeta and tau individually, as well as the intriguing possibility that
      misfolded Abeta acts as a template for tau misfolding in vivo.

PMID- 22965143
TI  - A critical role for phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac
      exchanger 1 in endothelial junction disruption and vascular hyperpermeability.
AB  - RATIONALE: The small GTPase Rac is critical to vascular endothelial functions,
      yet its regulation in endothelial cells remains unclear. Understanding the
      upstream pathway may delineate Rac activation mechanisms and its role in
      maintaining vascular endothelial barrier integrity. OBJECTIVE: By investigating
      phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 (P-Rex1),
      one of the Rac-specific guanine nucleotide exchange factors previously known for
      G protein-coupled receptor signaling, we sought to determine whether Rac-guanine
      nucleotide exchange factor is nodal for signal integration and potential target
      for drug intervention. METHODS AND RESULTS: Using gene deletion and small
      interference RNA silencing approach, we investigated the role of P-Rex1 in human
      lung microvascular endothelial cells. Tumor necrosis factor alpha (TNF-alpha)
      exposure led to disruption of endothelial junctions, and silencing P-Rex1
      protected junction integrity. TNF-alpha stimulated Rac activation and reactive
      oxygen species production in a P-Rex1-dependent manner. Removal of P-Rex1
      significantly reduced intercellular adhesion molecule-1 expression,
      polymorphonuclear leukocyte transendothelial migration, and leukocyte
      sequestration in TNF-alpha-challenged mouse lungs. The P-Rex1 knockout mice were
      also refractory to lung vascular hyperpermeability and edema in a
      lipopolysaccharide-induced sepsis model. CONCLUSIONS: These results demonstrate
      for the first time that P-Rex1 expressed in endothelial cells is activated
      downstream of TNF-alpha, which is not a G protein-coupled receptor agonist. Our
      data identify P-Rex1 as a critical mediator of vascular barrier disruption.
      Targeting P-Rex1 may effectively protect against TNF-alpha- and
      lipopolysaccharide-induced endothelial junction disruption and vascular
      hyperpermeability.

PMID- 22965145
TI  - GLIDE: GPU-based linear regression for detection of epistasis.
AB  - Due to recent advances in genotyping technologies, mapping phenotypes to single
      loci in the genome has become a standard technique in statistical genetics.
      However, one-locus mapping fails to explain much of the phenotypic variance in
      complex traits. Here, we present GLIDE, which maps phenotypes to pairs of genetic
      loci and systematically searches for the epistatic interactions expected to
      reveal part of this missing heritability. GLIDE makes use of the computational
      power of consumer-grade graphics cards to detect such interactions via linear
      regression. This enabled us to conduct a systematic two-locus mapping study on
      seven disease data sets from the Wellcome Trust Case Control Consortium and on in
      house hippocampal volume data in 6 h per data set, while current single CPU-based
      approaches require more than a year's time to complete the same task.

PMID- 22965144
TI  - Formation of the collateral circulation is regulated by vascular endothelial
      growth factor-A and a disintegrin and metalloprotease family members 10 and 17.
AB  - RATIONALE: The density of native (preexisting) collaterals varies widely and is a
      significant determinant of variation in severity of stroke, myocardial
      infarction, and peripheral artery disease. However, little is known about
      mechanisms responsible for formation of the collateral circulation in healthy
      tissues. OBJECTIVE: We previously found that variation in vascular endothelial
      growth factor (VEGF) expression causes differences in collateral density of
      newborn and adult mice. Herein, we sought to determine mechanisms of
      collaterogenesis in the embryo and the role of VEGF in this process. METHODS AND
      RESULTS: Pial collaterals begin forming between embryonic day 13.5 and 14.5 as
      sprout-like extensions from arterioles of existing cerebral artery trees. Global
      VEGF-A overexpressing mice (Vegf(hi/+)) formed more, and Vegf(lo/+) formed fewer,
      collaterals during embryogenesis, in association with differences in vascular
      patterning. Conditional global reduction of Vegf or Flk1 only during
      collaterogenesis significantly reduced collateral formation, but now without
      affecting vascular patterning, and the effects remained in adulthood. Endothelial
      specific Vegf reduction had no effect on collaterogenesis. Endothelial-specific
      reduction of a disintegrin-and-metalloprotease-domain-10 (Adam10) and inhibition
      of gamma-secretase increased collateral formation, consistent with their roles in
      VEGF-induced Notch1 activation and suppression of prosprouting signals.
      Endothelial-specific knockdown of Adam17 reduced collateral formation, consistent
      with its roles in endothelial cell migration and embryonic vascular
      stabilization, but not in activation of ligand-bound Notch1. These effects also
      remained in adulthood. CONCLUSIONS: Formation of pial collaterals occurs during a
      narrow developmental window via a sprouting angiogenesis-like mechanism, requires
      paracrine VEGF stimulation of fetal liver kinase 1-Notch signaling, and adult
      collateral number is dependent on embryonic collaterogenesis.

PMID- 22965146
TI  - Perceptual market orientation gap and its impact on relationship quality and
      patient loyalty: the role of internal marketing.
AB  - The purpose of this study was to explore the perceptual market orientation gaps
      between physician and patients and its impact on relationship quality and patient
      loyalty, and to verify the critical role of internal marketing on developing
      market orientation. Self-administered questionnaires were then employed to
      collect the data. We used a convenience sample of physicians and patients at a
      medical center in central Taiwan, and 90 usable questionnaires from physicians
      and 450 usable questionnaires from patients were returned. Hierarchical multiple
      regression analyses were used to validate the research hypotheses. Physicians'
      perceptual market orientation had a positive influence on physician-patient
      relationship quality, hospital-patient relationship quality, and patient loyalty,
      but the perceptual market orientation gap between physicians and their patients
      had a direct negative impact on these constructs. Finally, internal marketing was
      found to have an influence on relationship quality and patient loyalty through
      the mediation of market orientation. In order to enhance relationship quality and
      patient loyalty, hospital managers should focus their efforts on improving
      employees' market orientation and reducing patients' perceptual market
      orientation gap. In addition, internal marketing was found to be a useful pathway
      in developing market orientation.

PMID- 22965148
TI  - Breast cancer: Risk of death not increased for patients with dense breasts.

PMID- 22965147
TI  - The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein
      intracellular domain-overexpressing animals from Alzheimer's disease-like
      pathological features.
AB  - BACKGROUND: Amyloid-beta (Abeta) peptides derive from the amyloid precursor
      protein (APP) and play a pivotal role in Alzheimer's disease (AD) pathogenesis.
      Our previous work showed that the APP intracellular domain (AICD), which is
      produced simultaneously with Abeta, also contributes to the development of AD
      like features. Studies show that administration of apolipoprotein E (apoE) and
      apoE-derived small peptide mimetics protect AD mouse models against these AD-like
      features. However, the effects of apoE-mimetic treatment on AICD-mediated AD-like
      pathologies remain to be elucidated. OBJECTIVE: To study the effects of an apoE
      mimetic (COG112) on neuroinflammation, hyperphosphorylation of tau and defects in
      adult neurogenesis in AICD- overexpressing transgenic mice (FeCgamma25 line).
      METHODS: Beginning at 1 month of age, animals were administered subcutaneous
      COG112 3 times per week for 3 months, followed by immunohistochemical analysis
      for neuroinflammation, neurogenesis and phosphorylated tau. RESULTS: Treatment
      with COG112 significantly reduced neuroinflammation in AICD mice and protected
      against impaired adult hippocampal neurogenesis. We also found that COG112
      treatment reduced hyperphosphorylation and somatodendritic accumulation of tau in
      the hippocampus and cerebral cortex of AICD mice. CONCLUSIONS: Reduction of
      neuroinflammation by the apoE-mimetic COG112 protects against impaired
      neurogenesis and tau pathology in AICD transgenic mice. These data suggest that
      neuroinflammation plays an important role in AICD-induced AD-like pathologies.

PMID- 22965150
TI  - Screening: Cervical cancer--should we abandon cytology for screening?

PMID- 22965149
TI  - What are we learning from the cancer genome?
AB  - Massively parallel approaches to nucleic acid sequencing have matured from proof
      of-concept to commercial products during the past 5 years. These technologies are
      now widely accessible, increasingly affordable, and have already exerted a
      transformative influence on the study of human cancer. Here, we review new
      features of cancer genomes that are being revealed by large-scale applications of
      these technologies. We focus on those insights most likely to affect future
      clinical practice. Foremost among these lessons, we summarize the formidable
      genetic heterogeneity within given cancer types that is appreciable with higher
      resolution profiling and larger sample sets. We discuss the inherent challenges
      of defining driving genomic events in a given cancer genome amidst thousands of
      other somatic events. Finally, we explore the organizational, regulatory and
      societal challenges impeding precision cancer medicine based on genomic profiling
      from assuming its place as standard-of-care.

PMID- 22965152
TI  - Breast cancer: Cancer in pregnancy, to treat or not to treat?

PMID- 22965151
TI  - From drug discovery to biomarker-driven clinical trials in lymphoma.
AB  - Over the past three decades, the pathological classification of lymphoma has
      substantially improved. The early Rappaport classification included a handful of
      subtypes that did not reflect the cell of origin and, not surprisingly, resulted
      in diagnostic inaccuracies. The WHO currently classifies lymphoma into 30 major
      distinctive types. While this classification improved the accuracy and
      consistency of the histological diagnosis of lymphoma, it had little impact on
      advancing drug development or improving the cure rate of this disease. One reason
      for this lack of improvement is that recent developments in cancer genomics show
      these histopathological subtypes to be heterogeneous. Basing treatment decisions
      on histopathological subtypes is inefficient as it groups different underlying
      molecular characteristics into one category. Such a strategy exposes many
      patients to potentially toxic drugs without providing benefits. The recent
      approval of two new cancer drugs with companion diagnostics to allow selection
      and treatment of patients with melanoma and non-small-cell lung cancer has raised
      hope that a similar approach may also expedite successful drug development in
      lymphoma. We review the current status of biomarker development in lymphoma, and
      discuss novel biomarker-directed clinical trial designs for lymphoma.

PMID- 22965153
TI  - Pancreatic cancer: Is it time for Dr Whipple's orphans to have a Facebook page?

PMID- 22965155
TI  - Gastrointestinal cancer: New drug shows promise in refractory colorectal cancer.

PMID- 22965156
TI  - Thermoelectric properties of armchair and zigzag silicene nanoribbons.
AB  - Using the nonequilibrium Green's function method and nonequilibrium molecular
      dynamics simulations, we discuss the possibility of using silicene nanoribbons
      (SiNRs) as high performance thermoelectric materials. It is found that SiNRs are
      structurally stable if the edge atoms are passivated by hydrogen, and those with
      armchair edges usually exhibit much better thermoelectric performance than their
      zigzag counterparts. The room temperature ZT value of armchair SiNRs shows a
      width-dependent oscillating decay, while it decreases slowly with increasing
      ribbon width for the zigzag SiNRs. In addition, there is a strong temperature
      dependence of the thermoelectric performance of these SiNRs. Our theoretical
      calculations indicate that by optimizing the doping level and applied
      temperature, the ZT value of SiNRs could be enhanced to as high as 4.9 which
      suggests their very appealing thermoelectric applications.

PMID- 22965154
TI  - Targeted therapy in rare cancers--adopting the orphans.
AB  - Designation of a rare 'orphan' disease is usually conferred by a prevalence of
      one in 1,500 to 2,500 individuals. Increasingly, orphan diseases are also being
      defined by their molecular fingerprints. Rare diseases are uniquely challenging
      from a therapeutic standpoint; it is critical to modify clinical study design of
      treatments for orphan disorders as well as for the increasingly smaller molecular
      subsets within frequently occurring cancers. In spite of the immense challenges
      associated with developing a treatment for a rare disorder, some of the most
      groundbreaking therapeutic discoveries have been made in orphan malignancies.
      This situation may be because a limited number of driver molecular aberrations
      occur in rare disorders, which can be targeted by agents. Here, we describe drug
      class examples of targeted therapies for orphan diseases, with particular
      emphasis on malignancies or tumour-prone nonmalignant conditions, as well as
      potential therapeutic strategies that can be adopted to treat these orphan
      conditions.

PMID- 22965157
TI  - Hepatitis B screening in a US academic primary care practice.

PMID- 22965158
TI  - Parstatin prevents renal injury following ischemia/reperfusion and radiocontrast
      administration.
AB  - BACKGROUND/AIMS: Parstatin is a 41-mer peptide formed by proteolytic cleavage on
      activation of the protease-activated receptor 1. Parstatin was recently found to
      be cardioprotective against myocardial ischemia/reperfusion (IR) injury. In the
      present study, it was hypothesized that parstatin would protect the kidneys in
      acute renal failure. METHODS: We investigated the effects of parstatin on the
      renal dysfunction and injury caused either by renal IR injury or contrast-induced
      nephropathy (CIN) in two animal models. Renal IR injury was induced in rats by
      bilateral occlusion of renal arteries and veins for 45 min followed by 4 h of
      reperfusion, while CIN was induced in rabbits by intravenous injection of the
      radiocontrast medium Iopromide. RESULTS: Treatment with parstatin 15 min before
      or immediately after renal ischemia attenuated the resulting renal dysfunction as
      demonstrated by the improved biochemical indicators (serum creatinine and
      fractional excretion of Na(+)) and scintigraphic analysis. The effect was dose
      depended and provided evidence for a more prominent protection of tubular than
      glomerulal function. Histopathological examination of the kidneys revealed severe
      renal damage, which was significantly suppressed by the parstatin. Similarly,
      administration of a single dose of parstatin before the induction of CIN
      significantly protected against the resulting renal dysfunction and
      histologically evidenced renal tubular injury. CONCLUSION: These results suggest
      that parstatin is able to act as nephroprotective agent and may be useful in
      enhancing the tolerance of the kidney against renal injury associated with
      clinical conditions of acute renal failure. Further investigation on the
      mechanism underlying the nephroprotective properties of parstatin is deemed
      necessary.

PMID- 22965159
TI  - Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to
      avoid early cystectomy?.
AB  - OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high
      recurrence rate after primary transurethral resection. In case of bacillus
      Calmette-Guerin-refractory neoplasms, cystectomy is the gold standard. In this
      study the effects of thermochemotherapy with mitomycin C were evaluated in high
      risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS:
      Between January 2006 and December 2009, 30 patients were enrolled with recurrent
      stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder
      cancer refractory to chemotherapy or immunotherapy and so becoming suitable for
      radical cystectomy. All patients underwent endovesical thermochemotherapy: 16
      patients underwent a prophylactic scheme and 14 patients underwent an ablative
      scheme. RESULTS: All the patients completed the study. The mean follow-up for all
      the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were
      disease free and 17 patients (56.70%) had recurrence. In the prophylactic group,
      7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor
      recurrence; no progression was observed. In the ablative group, 3 patients (17,
      64%) had progression to muscle-invasive disease. Side effects were generally
      mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in
      patients refractory to intravesical therapies before considering early
      cystectomy.

PMID- 22965161
TI  - Identification of metabolic biomarkers for personalized nutrition.

PMID- 22965160
TI  - Consequences of stopping and restarting leptin in an adolescent with
      lipodystrophy.
AB  - BACKGROUND/AIMS: Lipodystrophy encompasses a group of rare disorders
      characterized by deficiency of adipose tissue resulting in hypoleptinemia, and
      metabolic abnormalities including insulin resistance, diabetes, dyslipidemia, and
      nonalcoholic steatohepatitis. Leptin replacement effectively ameliorates these
      metabolic derangements. We report effects of leptin discontinuation and
      resumption in a child with acquired generalized lipodystrophy. METHODS:
      Intermittent treatment with leptin with follow-up over 5 years. RESULTS:
      Pretreatment metabolic abnormalities included insulin resistance,
      hypertriglyceridemia and steatohepatitis. Leptin was started at the age of 10
      years. After 2 years, the family requested discontinuation of leptin due to lack
      of visible physical changes. Nine months later, worsened metabolic abnormalities
      and arrest of pubertal development were observed. Leptin was restarted, followed
      by improvements in metabolic parameters. Laboratory changes (before vs. 6 months
      after restarting leptin) were: fasting glucose from 232 to 85 mg/dl, insulin from
      232 to 38.9 uU/ml, HbA(1c) from 7.5 to 4.8%, triglycerides from 622 to 96 mg/dl,
      ALT from 229 to 61 U/l, AST from 91 to 18 U/l, and urine protein:creatinine ratio
      from 5.4 to 0.3. Progression of puberty was observed 1 year after restarting
      leptin. CONCLUSION: Initial leptin therapy likely prevented progression of
      metabolic abnormalities. Treatment discontinuation led to rapid metabolic
      decomposition and pubertal arrest. Reintroduction of leptin reversed metabolic
      abnormalities and allowed normal pubertal progression.

PMID- 22965162
TI  - Glioblastoma resistance to anti-VEGF therapy is associated with myeloid cell
      infiltration, stem cell accumulation, and a mesenchymal phenotype.
AB  - Vascular endothelial growth factor (VEGF) is a critical regulator of
      angiogenesis. Inhibiting the VEGF-VEGF receptor (R) signal transduction pathway
      in glioblastoma has recently been shown to delay progression, but the relative
      benefit and mechanisms of response and failure of anti-VEGF therapy and VEGFR
      inhibitors are not well understood. The purpose of our study was to evaluate the
      relative effectiveness of VEGF sequestration and/or VEGFR inhibition on
      orthotopic tumor growth and the mechanism(s) of treatment resistance. We
      evaluated, not only, the effects of anti-VEGF therapy (bevacizumab), anti-VEGFR
      therapy (sunitinib), and the combination on the survival of mice bearing
      orthotopic gliomas, but also the differential effects of the treatments on tumor
      vascularity, cellular proliferation, mesenchymal and stem cell markers, and
      myeloid cell infiltration using flow cytometry and immunohistochemistry.
      Bevacizumab significantly prolonged survival compared with the control or
      sunitinib alone. Both antiangiogenic agents initially reduced infiltration of
      macrophages and tumor vascularity. However, multitargeted VEGFR inhibition, but
      not VEGF sequestration, rapidly created a vascular gradient and more rapidly
      induced tumor hypoxia. Re-infiltration of macrophages was associated with the
      induction of hypoxia. Combination treatment with bevacizumab and sunitinib
      improved animal survival compared with bevacizumab therapy alone. However, at the
      time of tumor progression, a significant increase in CD11b(+)/Gr1(+) granulocyte
      infiltration was observed, and tumors developed aggressive mesenchymal features
      and increased stem cell marker expression. Collectively, our results demonstrate
      a more prolonged decrease in tumor vascularity with bevacizumab than with
      sunitinib, associated with a delay in the development of hypoxia and sustained
      reduction of infiltrated myeloid cells.

PMID- 22965165
TI  - Diabetes: unhealthy lifestyle and obesity explain half of socioeconomic
      differences in T2DM.

PMID- 22965166
TI  - Gut microbiota: adding weight to the microbiota's role in obesity--exposure to
      antibiotics early in life can lead to increased adiposity.

PMID- 22965164
TI  - Managing type 1 diabetes mellitus in pregnancy--from planning to breastfeeding.
AB  - Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes
      for mother and offspring. Careful preconception counselling and screening is
      important, with particular focus on glycaemic control, indications for
      antihypertensive therapy, screening for diabetic nephropathy, diabetic
      retinopathy and thyroid dysfunction, as well as review of other medications.
      Supplementation with folic acid should be initiated before conception in order to
      minimize the risk of fetal malformations. Obtaining and maintaining tight control
      of blood glucose and blood pressure before and during pregnancy is crucial for
      optimizing outcomes; however, the risk of severe hypoglycaemia during pregnancy
      is a major obstacle. Although pregnancy does not result in deterioration of
      kidney function in women with diabetic nephropathy and normal serum creatinine
      levels, pregnancy complications such as pre-eclampsia and preterm delivery are
      more frequent in these women than in women with T1DM and normal kidney function.
      Rapid-acting insulin analogues are considered safe to use in pregnancy and
      studies on long-acting insulin analogues have provided reassuring results.
      Immediately after delivery the insulin requirement declines to approximately 60%
      of the prepregnancy dose, and remains 10% lower than before pregnancy during
      breastfeeding.

PMID- 22965163
TI  - Adrenal disorders in pregnancy.
AB  - Pregnancy is marked by alterations in a number of endocrine systems, including
      activation of the renin-angiotensin-aldosterone system and the hypothalamic
      pituitary-adrenal axis. The placenta, the fetal adrenal glands and the liver
      constitute an interactive endocrine entity, known as the fetoplacental unit. In
      the fetoplacental unit, the fetal adrenal glands are the primary source of
      dehydroepiandrosterone sulphate, which is further metabolized by the fetal liver
      and placenta to produce a variety of oestrogens. Several disorders can affect
      both the fetal and maternal adrenal glands during pregnancy. The most common
      fetal adrenal disorder, steroid 21-hydroxylase deficiency, leads to abnormalities
      in sexual development and can be life threatening for the neonate. Although rare,
      maternal adrenal disorders are associated with considerable maternal mortality
      and morbidity if not promptly recognized and treated. However, diagnosis is often
      difficult to establish because of the endocrine changes occurring during normal
      pregnancies and the lack of reference values for the majority of the adrenal
      steroids. This Review provides an overview of adrenal steroid metabolism during
      pregnancy and focuses on diagnosis and treatment of the most common fetal and
      maternal adrenal disorders.

PMID- 22965167
TI  - Ethics: Genetic testing for MEN1--whose responsibility?

PMID- 22965168
TI  - Obesity: health economics of bariatric surgery--benefit versus cost.

PMID- 22965169
TI  - Innate immunity regulates adaptive immune response: lessons learned from studying
      the interplay between NK and CD8+ T cells during MCMV infection.
AB  - Natural killer (NK) cells play a crucial role in early immune response against
      cytomegalovirus infection. A large and mounting body of data indicate that these
      cells are involved in the regulation of the adaptive immune response as well. By
      using mouse cytomegalovirus (MCMV) as a model, several groups provided novel
      insights into the role of NK cells in the development and kinetics of antiviral
      CD8(+) T cell response. Depending on infection conditions, virus strain and the
      genetic background of mice used, NK cells are either positive or negative
      regulators of the CD8(+) T cell response. At present, there is no unique
      explanation for the observed differences between various experimental systems
      used. In this review we discuss the mechanisms involved in the interplay between
      NK and CD8(+) T cells in the early control of MCMV infection.

PMID- 22965170
TI  - Live or let die: manipulation of cellular suicide programs by murine
      cytomegalovirus.
AB  - Cytomegaloviruses (CMVs) are large double-stranded DNA viruses that replicate
      slowly and cause life-long persisting infections in their hosts. To achieve this,
      the CMVs had to evolve numerous countermeasures against innate and adaptive
      immune responses. Induction of programmed cell death is one important host
      defense mechanism against intracellular pathogens such as viruses. For a
      multicellular organism, it is advantageous to let infected cells die in order to
      thwart viral replication and dissemination. For a virus, by contrast, it is
      better to inhibit cell death and keep infected cells alive until the viral
      replication cycle has been completed. As a matter of fact, the CMVs encode a
      number of proteins devoted to interfering with different forms of programmed cell
      death: apoptosis and necroptosis. In this review, we summarize the known
      functions of the four best characterized cell death inhibitors of murine
      cytomegalovirus (MCMV), which are encoded by open reading frames, M36, m38.5,
      m41.1, and M45. The viral proteins interact with key molecules within different
      cell death pathways, namely caspase-8, Bax, Bak, and RIP1/RIP3. In addition, we
      discuss which events during MCMV infection might trigger apoptosis or necrosis
      and how MCMV's countermeasures compare to those of other herpesviruses. Since
      both, MCMV and its natural host, are amenable to genetic manipulation, the mouse
      model for CMV infection provides a particularly suitable system to study
      mechanisms of cell death induction and inhibition.

PMID- 22965171
TI  - Host factors involved in hepatitis B virus maturation, assembly, and egress.
AB  - Hepatitis B virus (HBV) is a major cause of liver disease. Due to the tiny size
      of its genome, HBV depends on the critical interplay between viral and host
      factors for the generation of new viral particles from infected cells. Recent
      work has illuminated a multiplicity of spatially and temporally coordinated virus
      host interactions that accompany HBV particle genesis. These interactions include
      the requirement of cellular chaperones for the maturation of the three viral
      envelope proteins, the cellular factors involved in dynamic modification,
      maturation, and intracellular trafficking of the nucleocapsids, and the host
      components of the multivesicular body (MVB) pathway enabling virion budding at
      intracellular compartments. Beside infectious virions, HBV produces at least two
      other types of particles, subviral empty envelope particles and subviral naked
      capsid particles, likely as a result of the engagement of different host factors
      by the viral structural proteins. Accordingly, HBV exploits distinct cellular
      pathways to release its particle types. Here, I review recent progress in these
      areas of the cell biology of HBV genesis.

PMID- 22965172
TI  - Nucleocytoplasmic shuttling and CRM1-dependent MHC class I peptide presentation
      of human cytomegalovirus pp65.
AB  - The phosphoprotein 65 (pp65) of human cytomegalovirus is a prominent target of
      the antiviral CD8 T lymphocyte response. This study focused on investigating the
      properties of pp65 that render it a privileged antigen. It was found that pp65
      was metabolically stable. The tegument protein was introduced into MHC class I
      presentation following its delivery via non-replicating dense bodies. No
      ubiquitination was found on particle-associated pp65. Proof was obtained that
      pp65 was a nucleocytoplasmic shuttle protein, using heterokaryon analyses. Based
      on this finding, inhibition experiments showed that presentation of particle
      derived pp65 by HLA-A2 was sensitive to the impairment of the CRM1-mediated
      nuclear export pathway. The data support the idea that particle-derived pp65 can
      serve as a nuclear reservoir for proteasomal processing and MHC class I
      presentation, following its CRM1-dependent nuclear export. The presentation of
      pp65-derived peptides was also impaired by CRM1-inhibition following de novo
      synthesis of the tegument protein. However, pp65 protein levels were also reduced
      when blocking CRM1-mediated export after transient expression. This indicated
      that pp65 expression rather than direct interference with its own nuclear export
      was responsible for its reduced presentation in this case. The functionality of
      CRM1-mediated nuclear export is thus important for the presentation of pp65
      derived peptides in the context of MHC class I on organ cells, both after
      exogenous uptake and after de novo synthesis of the tegument protein, but
      different mechanisms may account for either case.

PMID- 22965173
TI  - Malaria and human red blood cells.
AB  - Invasion by the malaria parasite, Plasmodium falciparum, brings about extensive
      changes in the host red cells. These include loss of the normal discoid shape,
      increased rigidity of the membrane, elevated permeability to a wide variety of
      ionic and other species and increased adhesiveness, most notably to endothelial
      surfaces. These effects facilitate survival of the parasite within the host cell
      and tend to increase the virulence of disease that includes cerebral malaria and
      anemia. Numerous proteins secreted by the internalized parasite and interacting
      with red cell membrane proteins are responsible for the changes occurring to the
      host cell. Anemia, a serious clinical manifestation of malaria, is due to
      increased destruction of both infected and uninfected red cells due to membrane
      alterations, as well as ineffective erythropoiesis. There is very good evidence
      that various red cell disorders including hemoglobinopathies and hereditary
      ovalocytosis decrease the virulence of disease following parasite infection. A
      number of mechanism(s) are likely responsible for the protective effect of
      various red cell abnormalities including decreased invasion, impaired
      intraerythrocytic development of the parasites and altered interaction between
      exported parasite proteins and the red cell membrane skeleton.

PMID- 22965174
TI  - The microwave spectrum of neurotransmitter serotonin.
AB  - A laser ablation device in combination with a molecular beam Fourier-transform
      microwave spectrometer has allowed the observation of the rotational spectrum of
      serotonin for the first time. Three conformers of the neurotransmitter have been
      detected and characterized in the 4-10 GHz frequency range. The complicated
      hyperfine structure arising from the presence of two (14)N nuclei has been fully
      resolved for all conformers and used for their identification. Nuclear quadrupole
      coupling constants of the nitrogen atom of the side chain have been used to
      determine the orientation of the amino group probing the existence of N-Hpi
      interactions involving the amino group and the pyrrole unit in the Gauche-Phenyl
      conformer (GPh) or the phenyl unit in the Gauche-Pyrrole (GPy) ones.

PMID- 22965175
TI  - Size- and shape-dependent growth of fluorescent ZnS nanorods and nanowires using
      Ag nanocrystals as seeds.
AB  - High-quality, monodisperse, and size-controlled Ag-ZnS nanorods or nanowires have
      been synthesized successfully using Ag nanocrystals as seeds. Such one
      dimensional colloidal Ag-ZnS nanorods or nanowires having a purposefully
      controlled diameter in the range of 5-9 nm and a length of 18-600 nm were
      obtained by altering the reaction conditions, such as concentration, reaction
      time, reaction temperature, and diameter of Ag nanocrystals. The conjunction
      interface of Ag-ZnS nanorods or nanowires consists of the (200) plane of Ag
      nanocrystal and (101) plane of ZnS rod or wire, the <101> directions of ZnS
      nanorods grow preferentially. Based on the photoluminescence and lifetime of Ag
      ZnS nanorods, it was found that Ag nanocrystals enhanced the radiative rate
      eventually, the fluorescence intensity of Ag-ZnS nanorods can be tuned by
      changing the size of the Ag seeds. The Ag-ZnS nanorods or nanowires showed
      greatly improved optical properties as compared to ZnS nanocrystals, the maximum
      emission was around 402 nm and the photoluminescence quantum yield was up to 30%
      when 5 nm Ag nanocrystals were used as seeds.

PMID- 22965176
TI  - The impact of chronic obstructive pulmonary disease and smoking on mortality and
      kidney transplantation in end-stage kidney disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and tobacco use are
      leading causes of morbidity and mortality. The prevalence and clinical impact of
      COPD on mortality and kidney transplantation among patients who begin dialysis
      therapy is unclear. METHODS: We explored the clinical impact of COPD and
      continued tobacco use on overall mortality and kidney transplantation in a
      national cohort study of US dialysis patients. National data on all dialysis
      patients (n = 769,984), incident between May 1995 and December 2004 and followed
      until October 31, 2006, were analyzed from the United States Renal Data System.
      Prevalence and period trends were determined while multivariable Cox regression
      evaluated relative hazard ratios (RR) for death and kidney transplantation.
      RESULTS: The prevalence of COPD was 7.5% overall and increased from 6.7 to 8.1%
      from 1995-2004. COPD correlated significantly with older age, cardiovascular
      conditions, cancer, malnutrition, poor functional status, and tobacco use.
      Adjusted mortality risks were significantly higher for patients with COPD (RR =
      1.20, 95% CI 1.18-1.21), especially among current smokers (RR = 1.28, 95% CI 1.25
      1.32), and varied inversely with advancing age. In contrast, the adjusted risks
      of kidney transplantation were significantly lower for patients with COPD (RR =
      0.47, 95% CI 0.41-0.54, for smokers and RR = 0.54, 95% CI 0.50-0.58, for non
      smokers) than without COPD [RR = 0.72, 95% CI 0.70-0.75, for smokers and RR =
      1.00 for non-smokers (referent category)]. CONCLUSIONS: Patients with COPD who
      begin dialysis therapy in the US experience higher mortality and lower rates of
      kidney transplantation, outcomes that are far worse among current smokers.

PMID- 22965177
TI  - Visco-hyperelastic law for finite deformations: a frequency analysis.
AB  - Some biological tissues are repeatedly stimulated under cyclic loading, and this
      stimulation can be combined with large pressures, thus leading to large
      deformations. For such applications, visco-hyperelastic models have been proposed
      in the literature and used in finite-element studies. An extensively used quasi
      linear model (QLVH), which assumes linear evolution equations, is compared with a
      nonlinear model (NLVH), which assumes a multiplicative split of the deformation
      gradient. The comparison is made here using sets of simulations covering a large
      frequency range. Lost and stored energies are computed, and the additional
      parameter of the NLVH model is set to two values found in the literature (NLVH-2
      and NLVH-30 models). The predicted behaviour is very similar for all models at
      small strains, with each time constant (and corresponding viscous modulus) being
      associated with a damping peak and a stored-energy increase. When the strain
      amplitude is increased, the ratio of lost to stored energy increases for the QLVH
      model, but decreases for the NLVH models. The NLVH-30 model also displays a shift
      of the peak damping towards higher frequencies. Before reaching a steady state,
      all models display a decay of energy independent of the frequency, and the
      additional parameter of the NLVH model permits the modelling of complex types of
      evolution of the damping. In conclusion, this study compares the behaviour of two
      viscous hyper-elastic laws to allow an informed choice between them. 

PMID- 22965178
TI  - Different mechanisms of intestinal calcium absorption at different life stages:
      therapeutic implications and long-term responses to treatment in patients with
      hereditary vitamin D-resistant rickets.
AB  - BACKGROUND: Intestinal calcium absorption is regulated principally by 1,25
      dihydroxyvitamin D, but other regulators are also involved. CASE REPORT: The 3
      children studied were born with unaffected bones. Two were referred at 21 months
      of age, with clinical features of severe vitamin D-resistant rickets. They were
      treated with intravenous calcium for 12-18 months, following an initial lack of
      response to oral calcium and vitamin D. The third patient, who was exclusively
      breast-fed, was diagnosed at 4 months of age, due to alopecia. His condition was
      successfully managed with high doses of oral calcium and vitamin D. All 3
      patients were homozygous for a mutation in the DNA-binding domain of vitamin D
      receptor. At the most recent evaluation of these patients, currently maintained
      on oral calcium and vitamin D, clinical findings were normal. CONCLUSION: During
      gestation, calcium flux across the placenta is normal, preventing bone diseases
      in affected fetuses. High calcium intake early in life and, perhaps, the
      maintenance of breastfeeding for several months may constitute an effective
      approach to ensuring adequate absorption and preventing severe rickets. During
      childhood, after parenteral calcium treatment to bypass intestinal calcium
      absorption, it is possible to maintain normal bone through long-term oral calcium
      supplementation.

PMID- 22965179
TI  - [Extracorporeal circulation : from last resort to standard procedure].

PMID- 22965180
TI  - [Cerebral oximetry: clinical importance for cardiac surgery patients].
AB  - The determination of cerebral oxygen saturation (S(c)O(2)) by means of near
      infrared spectroscopy allows non-invasive assessment of the cerebral oxygen
      delivery and demand ratio in the frontal cortex region. Studies in cardiac as
      well as non-cardiac patients have shown that maintaining S(c)O(2) in the
      preoperative range reduces the incidence of postoperative cognitive dysfunction
      and general morbidity; however, S(c)O(2) is not only reflective of cerebral but
      also of systemic oxygen balance, is inversely related to cardiopulmonary function
      and has prognostic relevance in cardiac surgery patients. This suggests that
      cerebral oximetry is not only useful for neurological but also for hemodynamic
      monitoring and preoperative risk stratification of cardiac surgery patients.

PMID- 22965181
TI  - [Life-threatening opioid overdose. Decoding the physician pin code of a patient
      controlled anesthesia pump by patients].
AB  - Patient-controlled analgesia (PCA) is an established standard therapy for
      providing postoperative analgesia. To avoid possible abuse by patients each PCA
      pump is secured by a pin code that should be neither known nor accessible to
      patients. The two case reports described illustrate how manipulation of a PCA
      pump led to massive opioid abuse by the patients who decoded the pin code for
      unlimited additional doses. One patient developed withdrawal symptoms after
      switching the therapy and, as a consequence even had to be admitted to the
      intensive care unit (ICU). Easy access to the PCA pump codes on the internet for
      the patients and the impossibility of changing the pin codes by the medical staff
      played an important role in these two cases.

PMID- 22965182
TI  - [Medical further training in anesthesiology. Structuring of curricula and
      financing necessary].

PMID- 22965183
TI  - [Cessation of anesthesia after newly occurring anisocoria without light
      reflexes].
AB  - Anisocoria during general anaesthesia is rare. The combination of anisocoria and
      absence of any reaction to light is highly suspicious of an intracerebral lesion.
      This article reports the case of a patient with known Adie's syndrome where
      anisocoria led to an unnecessary immediate interruption of anesthesia. A
      preoperative examination, including inspection of the pupils, frequent
      perioperative check ups and documentation of diagnostic findings, even if
      negative, has to be standard for every anesthesia.

PMID- 22965184
TI  - [Life-saving air supported avalanche mission at night in high alpine terrain].
AB  - This is a case report about a helicopter emergency medical service (HEMS)
      operation during the night in response to an avalanche accident with two
      completely buried victims. One of the victims was rescued alive after 9.2 h
      presenting with a patent airway and an air pocket and was successfully rewarmed
      with forced air from 23 degrees C core temperature without any neurological
      deficits. After the rescue the patient developed lung edema which resolved
      spontaneously within 2 days. The second victim was found dead presenting with an
      air pocket but solid frozen thorax. The special circumstances of the rescue
      operation and treatment are presented and discussed. The impact of a frozen chest
      on resuscitation decisions is presented and discussed with an emphasis on the
      triage of multiple victims.

PMID- 22965185
TI  - A rare case of isolated kidney cysticercosis.
AB  - A rare case of isolated kidney cysticercosis is presented. Clinical signs and
      diagnostic findings are unspecific. They are discussed and a conservative
      therapeutic approach is suggested.

PMID- 22965187
TI  - Copy number polymorphism of the salivary amylase gene: implications in human
      nutrition research.
AB  - The salivary alpha-amylase is a calcium-binding enzyme that initiates starch
      digestion in the oral cavity. The alpha-amylase genes are located in a cluster on
      the chromosome that includes salivary amylase genes (AMY1), two pancreatic alpha
      amylase genes (AMY2A and AMY2B) and a related pseudogene. The AMY1 genes show
      extensive copy number variation which is directly proportional to the salivary
      alpha-amylase content in saliva. The alpha-amylase amount in saliva is also
      influenced by other factors, such as hydration status, psychosocial stress level,
      and short-term dietary habits. It has been shown that the average copy number of
      AMY1 gene is higher in populations that evolved under high-starch diets versus
      low-starch diets, reflecting an intense positive selection imposed by diet on
      amylase copy number during evolution. In this context, a number of different
      aspects can be considered in evaluating the possible impact of copy number
      variation of the AMY1 gene on nutrition research, such as issues related to human
      diet gene evolution, action on starch digestion, effect on glycemic response
      after starch consumption, modulation of the action of alpha-amylases inhibitors,
      effect on taste perception and satiety, influence on psychosocial stress and
      relation to oral health.

PMID- 22965188
TI  - Altered expression levels of HLA class II and costimulatory molecules on
      circulating monocytes from patients with cervical intraepithelial neoplasia and
      squamous cervical cancer.
AB  - The aim of this study was to investigate the role of the cell surface expression
      levels of HLA class I and II molecules, the costimulatory molecules CD80/B7-1 and
      CD86/B7-2, and the adhesion molecules CD54 and CD58 during cervical
      carcinogenesis. The expression levels of MHC class I and II molecules, the
      costimulatory molecules CD80/B7-1 and CD86/B7-2 and the adhesion molecules CD54
      and CD58 on CD14+ peripheral blood monocytes (PBMs) from 21 cases of cervical
      intraepithelial neoplasia (CIN) II-III, 51 squamous cervical carcinomas (SCCs)
      and 18 healthy controls were analyzed using flow cytometry analysis. We found
      increased expression levels of HLA-DR (p=0.000), HLA-DQ (p=0.000), CD86/B7-2
      (p=0.002) and CD58 (p=0.000) on PBMs from patients with SCC and CIN II-III,
      compared with healthy control subjects, whereas no significant difference existed
      in the expression levels of HLA class I antigens, HLA-DP CD80/B7-1 and CD54.
      Upregulated expression levels of HLA-DR, HLA-DQ, CD86/B7-2 and CD58 were
      associated with disease progression, indicating that an increased expression of
      HLA-DR, HLA-DQ, CD86/B7-2 and CD58 on PBMs may be correlated with the evolution
      of cervical cancer.

PMID- 22965189
TI  - Development of a two-stage feeding strategy based on the kind and level of
      feeding nutrients for improving fed-batch production of L-threonine by
      Escherichia coli.
AB  - Fed-batch fermentation is the predominant method for industrial production of
      amino acids. In this study, we comprehensively investigated the effects of four
      kinds of feeding nutrients and developed an accurate optimization strategy for
      fed-batch production of L-threonine. The production of L-threonine was severely
      inhibited when cell growth ceased in the bath culture. Similarly, L-threonine
      production was also associated with cell growth in the carbon-, phosphate-, and
      sulfate-limited fed-batch cultures, but the accumulation of L-threonine was
      markedly increased because of the extended production time in the growth stage.
      Interestingly, auxotrophic amino acid (L-isoleucine)-limited feeding promoted L
      threonine production over the non-growth phase. Metabolite analysis indicates
      that substantial production of acetate and glutamate and the resulting
      accumulation of ammonium may lead to the inhibition of L-threonine production.
      During the growth phase, the levels of L-isoleucine were accurately optimized by
      balancing cell growth and production with Pontryagin's maximum principle, basing
      on the relationship between the specific growth rate MU and specific production
      rate rho. Furthermore, the depletion of L-isoleucine and phosphate at the end of
      the growth phase favored the synthesis of L-threonine in the subsequent non
      growth phase. Combining the two-stage feeding profiles, the final L-threonine
      concentration and conversion rate were increased by 5.9- and 2.1-fold,
      respectively, compared to batch processes without feeding control. The
      identification of efficient feeding nutrient and the development of accurate
      feeding strategies provide potential guidelines for microbial production of amino
      acids.

PMID- 22965186
TI  - Acupuncture for chronic pain: individual patient data meta-analysis.
AB  - BACKGROUND: Although acupuncture is widely used for chronic pain, there remains
      considerable controversy as to its value. We aimed to determine the effect size
      of acupuncture for 4 chronic pain conditions: back and neck pain, osteoarthritis,
      chronic headache, and shoulder pain. METHODS: We conducted a systematic review to
      identify randomized controlled trials (RCTs) of acupuncture for chronic pain in
      which allocation concealment was determined unambiguously to be adequate.
      Individual patient data meta-analyses were conducted using data from 29 of 31
      eligible RCTs, with a total of 17 922 patients analyzed. RESULTS: In the primary
      analysis, including all eligible RCTs, acupuncture was superior to both sham and
      no-acupuncture control for each pain condition (P < .001 for all comparisons).
      After exclusion of an outlying set of RCTs that strongly favored acupuncture, the
      effect sizes were similar across pain conditions. Patients receiving acupuncture
      had less pain, with scores that were 0.23 (95% CI, 0.13-0.33), 0.16 (95% CI, 0.07
      0.25), and 0.15 (95% CI, 0.07-0.24) SDs lower than sham controls for back and
      neck pain, osteoarthritis, and chronic headache, respectively; the effect sizes
      in comparison to no-acupuncture controls were 0.55 (95% CI, 0.51-0.58), 0.57 (95%
      CI, 0.50-0.64), and 0.42 (95% CI, 0.37-0.46) SDs. These results were robust to a
      variety of sensitivity analyses, including those related to publication bias.
      CONCLUSIONS: Acupuncture is effective for the treatment of chronic pain and is
      therefore a reasonable referral option. Significant differences between true and
      sham acupuncture indicate that acupuncture is more than a placebo. However, these
      differences are relatively modest, suggesting that factors in addition to the
      specific effects of needling are important contributors to the therapeutic
      effects of acupuncture.

PMID- 22965190
TI  - Bioresolution of (R)-glycidyl azide by Aspergillus niger ZJUTZQ208: a new and
      concise synthon for chiral vicinal amino alcohols.
AB  - A newly isolated Aspergillus niger strain containing epoxide hydrolase was used
      to resolve racemic glycidyl azide and four derivatives to the (R)-enantiomers.
      After optimization of the biotransformation conditions, (R)-glycidyl azide was
      produced with good enantioselectivity (e.e.s > 95 %, E > 20). The substrate
      structure, pH, and reaction time were found to have profound influences on the
      catalytic property of A. niger ZJUTZQ208. Enantiopure glycidyl azide was further
      utilized to synthesize linezolid in good yield, indicating it is a new and
      concise synthon for chiral vicinal amino alcohols. Enzyme-substrate docking
      studies were carried out with glycidyl azide to study the selectivity of this
      strain.

PMID- 22965191
TI  - Triple channel responsive Cu2+ probe.
AB  - A simple, selective and sensitive Cu(II) probe is highlighted. It is noteworthy
      that this novel probe induces triple channel (colorimetric, fluorogenic and
      voltammetric) response to Cu(II) ions, which makes it viable for practical
      applications.

PMID- 22965192
TI  - Association between TNFRSF11B gene polymorphisms and history of ischemic stroke
      in Italian diabetic patients.
AB  - Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor
      necrosis factor receptor family and plays a role in atherosclerosis. The present
      study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved
      in ischemic stroke in an Italian population with diabetes. Participants in a
      retrospective case-control study included 364 diabetic patients (180 males, 184
      females) with history of ischemic stroke and 492 diabetic subjects without
      history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C
      polymorphisms of the OPG gene were analyzed by polymerase chain reaction and
      restriction fragment length polymorphism. We found that the T245G, T950C, and
      G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P <
      0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively)
      and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR
      3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We
      also found that these three polymorphisms act synergistically in patients with
      stroke history. The TNFRSF11B gene polymorphisms studied are associated with
      history of ischemic stroke and synergistic effects between these genotypes might
      be potential markers for cerebrovascular disorders.

PMID- 22965193
TI  - Combination of MEK-ERK inhibitor and hyaluronic acid has a synergistic effect on
      anti-hypertrophic and pro-chondrogenic activities in osteoarthritis treatment.
AB  - We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug
      such as hyaluronic acid (HA) given in combination with anti-inflammatory
      signalling agents such as mitogen-activated protein kinase kinase-extracellular
      signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in
      additive or synergistic effects on preventing the degeneration of articular
      cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human
      OA primary cells treated with either HA or U0126, or the combination of HA +
      U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was
      investigated by intra-articular delivery of either HA or U0126, or the
      combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting
      and zymography were performed to assess the expression of cartilage matrix
      proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive
      chondrocytes were significantly higher in OA samples compared with those in
      healthy control suggesting the pathological role of that pathway in OA. It was
      noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte
      hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP
      13), however, increased the levels of chondrogenic markers (COL2) compared to
      untreated or the application of HA or U0126 alone. In agreement with the results
      in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic
      improvement of cartilage in rat MSX OA model compared with untreated or the
      application of HA or U0126 alone. Our study suggests that the combination of HA
      and MEK-ERK inhibition has a synergistic effect on preventing cartilage
      degeneration.

PMID- 22965194
TI  - Endothelin-1 induces the transactivation of vascular endothelial growth factor
      receptor-3 and modulates cell migration and vasculogenic mimicry in melanoma
      cells.
AB  - Endothelin receptor B (ET(B)R) is a G-protein-coupled receptor overexpressed in
      melanoma, blood, and lymphatic endothelial cells. Given that aberrant signal
      transduction can be mediated through cross talk between receptors, here, we
      explore the functional relationship between ET(B)R and the vascular endothelial
      growth factor receptor (VEGFR)-3 system and how this cross talk might influence
      the aggressive behavior of melanoma cells. The expression of VEGFR-3 and its
      ligands, VEGF-C and VEGF-D, significantly increased after activating ET(B)R by ET
      1 in primary and metastatic melanoma cell lines. These effects, similarly to
      those induced by hypoxia, were mediated by hypoxia-inducible factor (HIF)-1alpha
      and HIF-2alpha. ET-1 caused the phosphorylation of VEGFR-3, which was accompanied
      by the activation of the downstream signaling molecules, such as MAPK and AKT.
      Inhibition of c-Src activity or silencing of the scaffold protein beta-arrestin-1
      reduced ET-1-induced VEGFR-3 phosphorylation, demonstrating that, upon ET-1
      stimulus, beta-arrestin-1 is involved with c-Src in the ET(B)R-mediated VEGFR-3
      transactivation. Moreover, ET-1 in combination with VEGF-C further increased
      VEGFR-3, MAPK, and AKT phosphorylation and markedly promoted cell migration and
      vasculogenic mimicry. Dual inhibition of ET(B)R and VEGFR-3 was required for the
      effective inhibition of these effects, as well as for VEGFR-3 phosphorylation,
      demonstrating that ET(B)R cross talk with VEGFR-3 enhances cell plasticity and
      motility. Finally, in melanoma xenografts, ET(B)R antagonist inhibited tumor
      growth and the activation of the VEGF-C/VEGFR-3 axis, indicating that targeting
      ET(B)R may improve melanoma treatment acting directly or indirectly by impairing
      ET(B)R cross talk with VEGFR-3.

PMID- 22965196
TI  - Geometrical stepper-guided navigation system for ProACT implant under transrectal
      ultrasound control: preliminary data.
AB  - PURPOSE: To describe a new geometrical stepper-guided navigation system for
      positioning ProACT(r). METHODS: The sizing of the stepper-guided navigation
      system was calculated using the distance from the ideal position of the device to
      anatomic referral points previously measured by ultrasound. The trocar and
      subsequently the device were maneuvered to the ideal position in accordance with
      the navigation system. MEASUREMENTS: Treatment efficacy was evaluated with daily
      pad count, 1-hour pad test, Incontinence Quality of Life questionnaire (IQoL),
      visual analog scale and overall impression. Complications, balloon volume and
      number of adjustments were reported at 1, 3, 6 and 12 months follow-up visits.
      RESULTS: Mean follow-up was 12 (range 3-19) months. Daily pad count showed 30
      patients (71%) dry and 9 patients (21%) improved. 1 hour pad test showed 28
      patients were dry (66%) and 11 patients improved (26%). IQoL increased from an
      average of 35.3 to 80. Average visual analog scale score was 8. Complications
      requiring device removal occurred in 3 patients (7%). Mean balloon volume was 3.1
      ml. CONCLUSIONS: The stepper-guided navigation system to implant ProACT is
      feasible and extremely reproducible making this procedure more standardized.

PMID- 22965195
TI  - O-1602, an atypical cannabinoid, inhibits tumor growth in colitis-associated
      colon cancer through multiple mechanisms.
AB  - Cannabinoids have antiinflammatory and antitumorigenic properties. Some
      cannabinoids, such as O-1602, have no or only little affinity to classical
      cannabinoid receptors but exert cannabinoid-like antiinflammatory effects during
      experimental colitis. Here, we investigated whether O-1602 shows antitumorigenic
      effects in colon cancer cells and whether it could reduce tumorigenesis in the
      colon in vivo. The colon cancer cell lines HT-29 and SW480 were used to study the
      effect of O-1602 on viability and apoptosis. The effect of O-1602 on tumor growth
      in vivo was studied in a colitis-associated colon cancer mouse model. O-1602
      decreased viability and induced apoptosis in colon cancer cells in a
      concentration-dependent manner (0.1-10 MUM). In the mouse model, treatment with O
      1602 (3 mg/kg, i.p., 12*) reduced tumor area by 50 % and tumor incidence by 30 %.
      Histological scoring revealed a significant decrease in tumor load. In tumor
      tissue, O-1602 decreased levels of proliferating cell nuclear antigen (PCNA),
      activation of oncogenic transcription factors STAT3 and NFkappaB p65, and
      expression of TNF-alpha while levels for proapoptotic markers, such as p53 and
      BAX, increased. The in vivo effects of O-1602 on PCNA, BAX, and p53 were also
      observed in colon cancer cells. The data provide a novel insight into
      antitumorigenic mechanisms of atypical cannabinoids. O-1602 exerts
      antitumorigenic effects by targeting colon cancer cells as well as
      proinflammatory pathways known to promote colitis-associated tumorigenesis. Due
      to its lack of central sedation, O-1602 could be an interesting compound for the
      treatment of colon and possibly other cancers.

PMID- 22965197
TI  - Touch the screen.

PMID- 22965198
TI  - Importance of orthotic subtalar alignment for development and gait of children
      with cerebral palsy.
AB  - PURPOSE: This case report addresses the assumption that ankle and foot orthoses
      assist children with cerebral palsy. KEY POINTS: Outcome research reports are not
      consistent. Clinical observations and research studies suggest that inappropriate
      fit and design of orthoses may contribute to poor outcomes. In particular,
      problems occur when the subtalar joint is out of alignment as children often
      compensate with unwanted movement patterns that affect progress, development, and
      function. Four cases are presented to demonstrate problems that can occur when
      ankle-foot or supramalleolar orthoses are not cast in subtalar neutral.
      CONCLUSION: Physical therapists can use their clinical observation skills to
      evaluate the proper fit and alignment of orthoses for children with cerebral
      palsy.

PMID- 22965199
TI  - Comparison of articulated and rigid ankle-foot orthoses in children with cerebral
      palsy:  a systematic review.
AB  - PURPOSE: The aim of this review was to compare the effects of rigid and
      articulated ankle-foot orthoses on gait in children with cerebral palsy (CP).
      METHOD: A systematic review was carried out in 4 databases. The papers identified
      were evaluated on the basis of the following inclusion criteria: (1) design-
      controlled clinical trial; (2) population--children and adolescents with CP; (3)
      intervention--rigid or articulated ankle-foot orthoses; and (4) outcome--improved
      motor function and gait performance. RESULTS: Seven controlled studies comparing
      the effects of different ankle-foot orthoses were found. Studies achieved PEDro
      scores of 3 and 4 for methodological quality. CONCLUSION: There is evidence
      supporting the use of an articulated ankle-foot orthosis by children with CP,
      because of the improved function this type of orthosis provides. However, other
      studies point out the advantages of a rigid orthosis for children with greater
      impairment related to spasticity and contractures.

PMID- 22965200
TI  - What to measure when determining orthotic needs in children with Down syndrome: a
      pilot study.
AB  - PURPOSE: To compare the effects of off-the-shelf foot orthoses and supramalleolar
      orthoses on the gait of children with Down syndrome (DS), and establish criteria
      for determining orthoses prescription for a child with DS. METHODS: We assessed
      the gait of 6 children (aged 4-7 years) with DS using the GAITRite system, and
      obtained height, weight, leg length, hypermobility, calcaneal eversion, navicular
      drop, and tibial torsion measurements. RESULTS: Supramalleolar orthoses lead to a
      longer cycle time than foot orthoses (P = .05) and barefoot walking (P = .03) and
      a lower cadence than barefoot walking (P = .04). Significant strong correlations
      with gait parameters were obtained for height, leg length, and hypermobility.
      Biomechanical measurements showed no significant correlations with gait
      parameters. CONCLUSIONS: The role of physical examination data, including
      anthropometric and biomechanical measurements in the prescription of orthoses
      requires further investigation.

PMID- 22965201
TI  - Commentary on "What to measure when determining orthotic needs in children with
      Down syndrome: a pilot study".

PMID- 22965202
TI  - The use of TheraTogs versus twister cables in the treatment of in-toeing during
      gait in a child with spina bifida.
AB  - PURPOSE: To present the effects of TheraTogs and twister cables (TCs) on in
      toeing during gait in a child with spina bifida while comparing overall parent
      and patient satisfaction. CASE DESCRIPTION: The participant was a 2-year-old girl
      with L4 spina bifida with bilateral in-toeing during gait. INTERVENTION: The
      child was given a 6-week intervention of TheraTogs followed by 6 weeks of TCs.
      OUTCOMES: Kinematic data indicated optimal foot progression with the use of TCs,
      achieved by the rotation of the lower leg. Gait data for the use of TheraTogs
      indicated improved foot progression with external rotation at the hips. Gait
      characteristics indicated improved gait velocity in TheraTogs, but stride length
      was better with TCs. The parent reported satisfaction and preference for
      TheraTogs. CONCLUSION: As the first step in investigating the 2 interventions,
      both TheraTogs and TCs were effective in management of in-toeing for the child
      but parental preference favored TheraTogs.

PMID- 22965203
TI  - Reference values for the muscle power sprint test in 6- to 12-year-old children.
AB  - PURPOSE: The aims of this study were (1) to develop centile reference values for
      anaerobic performance of Dutch children tested using the Muscle Power Sprint Test
      (MPST) and (2) to examine the test-retest reliability of the MPST. METHODS:
      Children who were developing typically (178 boys and 201 girls) and aged 6 to 12
      years (mean = 8.9 years) were recruited. The MPST was administered to 379
      children, and test-retest reliability was examined in 47 children. MPST scores
      were transformed into centile curves, which were created using generalized
      additive models for location, scale, and shape. RESULTS: Height-related reference
      curves were created for both genders. Excellent (intraclass correlation
      coefficient = 0.98) test-retest reliability was demonstrated. CONCLUSIONS: The
      reference values for the MPST of children who are developing typically and aged 6
      to 12 years can serve as a clinical standard in pediatric physical therapy
      practice. The MPST is a reliable and practical method for determining anaerobic
      performance in children.

PMID- 22965204
TI  - Commentary on "Reference values for the muscle power sprint test in 6- to 12-year
      old children".

PMID- 22965205
TI  - Limb length discrepancies among 8- to 12-year-old children who are developing
      typically.
AB  - PURPOSE: The prevalence of lower extremity limb length discrepancy (LLD) in the
      general pediatric population has not been clearly defined. The goal of this study
      was to identify the prevalence of LLD in children aged 8 to 12 years, who are
      developing typically. METHODS: A convenience sample of 43 girls and 62 boys was
      tested. Participants' gender, age, height, and weight were recorded. Limb length
      measurements were taken from the anterior superior iliac spine to the medial
      malleolus and umbilicus to medial malleolus using the direct method. RESULTS:
      Descriptive statistics revealed an average age of 9.88 years (SD = 1.2), height
      of 55.7 inches (SD = 4.6), and weight of 82.5 pounds (SD = 24.6). Seven of 105
      children demonstrated an LLD of 2 cm or greater. CONCLUSION: Approximately 7% of
      the children present with an LLD of 2 cm or greater. This study contributes to
      the understanding of the prevalence of LLD in prepubescent children.

PMID- 22965206
TI  - Commentary on "Limb length discrepancies among 8- to 12-year-old children who are
      developing typically".

PMID- 22965207
TI  - Pain, balance, activity, and participation in children with hypermobility
      syndrome.
AB  - PURPOSE: To describe hypermobility, balance, pain, activity, and participation in
      children with hypermobility and compare these characteristics with those of a
      control group. METHOD: Twenty children aged 8 to 16 years with hypermobility
      syndrome (HMS) or Ehlers-Danlos syndrome and a control group of 24 children of
      the same age participated in the study. Hypermobility was assessed according to
      the Del Mar scale, balance was assessed with the Bruininks-Oseretsky test of
      motor proficiency, and participation in daily life activities was assessed with
      the frequency of participation questionnaire. Pain and physical activity were
      assessed in a diary. RESULTS: In comparison with the control group, the children
      with hypermobility had significantly more hypermobile joints and more pain and
      scored lower in the balance test, and their activity was affected on a daily
      basis. CONCLUSION: Pain appears to affect activity and participation in children
      with HMS. Balance is decreased in children with HMS compared with healthy
      controls.

PMID- 22965208
TI  - Commentary on "Pain, balance, activity, and participation in children with
      hypermobility syndrome".

PMID- 22965209
TI  - Concurrent validity of the Bayley-III and the Peabody Developmental Motor Scale
      2.
AB  - PURPOSE: To determine concurrent validity of the Bayley Scales of Infant and
      Toddler Development, Third Edition (Bayley-III) and the Peabody Developmental
      Motor Scales, Second Edition (PDMS-2). METHOD: Tests were administered to 48
      children with corrected age ranging from 29 days to 26 months. Concurrent
      validity between age-equivalent (AE) scores and standard scores was assessed for
      4 age groups. RESULTS: Moderate to very high correlation for all groups was found
      between the Bayley-III composite scores and the PDMS-2 Total Motor quotient
      scores. High correlations were found between the Bayley-III composite scores and
      the PDMS-2 Gross and Fine Motor quotients (12-26 months); high correlations were
      found between the Bayley-III and the PDMS-2 Gross Motor quotient (6-12 months)
      and moderate correlations were found for younger age groups. High concurrent
      validity for AE scores was found only above 18 months. CONCLUSIONS: The study
      supports the substitution of the Bayley-III for the PDMS-2 for standard scores or
      AE scores for children aged 19 to 26 months and for standard scores for children
      birth to 18 months.

PMID- 22965210
TI  - Commentary on "Concurrent validity of the Bayley-III and the Peabody
      Developmental Motor Scale-2".

PMID- 22965212
TI  - Commentary on "Weight status and gross motor skill in kindergarten children".

PMID- 22965211
TI  - Weight status and gross motor skill in kindergarten children.
AB  - PURPOSE: Childhood obesity rates are increasing globally. Physical activity is
      one behavioral variable that influences weight status. Participation in physical
      activity requires basic gross motor proficiency in early childhood. The purpose
      of this study was to examine the relationship between gross motor skill level and
      weight status in a large national representative sample of kindergarten-aged
      children. METHODS: Body mass index percentile ranking was calculated for 4650
      children from the Early Childhood Longitudinal Study-Birth Cohort. Children were
      classified into underweight, healthy, overweight, or obese categories according
      to the Centers for Disease Control and Prevention criteria. The Early Screening
      Inventory Revised was used to evaluate gross motor skill level. RESULTS: Children
      with obesity displayed lower gross motor skill levels compared with peers of
      healthy weight. Largest differences were seen in locomotor and balance skills.
      CONCLUSIONS: Clinicians should consider adjusting gross motor expectations for
      locomotor or stability tasks in young children with obesity.

PMID- 22965213
TI  - The psychosocial benefits of an inclusive community-based aquatics program.
AB  - PURPOSE: To examine the psychosocial effect of participation in an inclusive
      community-based aquatics program for children with and without disabilities.
      METHODS: Twenty-three participants completed an 8-week inclusive aquatics
      program. Quality of life, self-concept, and acceptance were measured using the
      PedsQL 4.0, Piers-Harris 2 Children's Self-Concept Scale, and Peer Sociometric
      Nomination Assessment (Friendship Questionnaire). Data were analyzed using a 2 *
      2 analysis of variance with repeated measures. RESULTS: After the 8-week
      intervention, a statistically significant decrease was found on the School
      subsection of the PedsQL 4.0 for the children without disabilities, and in the
      happiness subsection of the Piers-Harris 2 for the children with disabilities.
      The Peer Sociometric Nomination Assessment showed a trend that children with
      disabilities received less negative peer nominations at posttest when compared
      with pretest. CONCLUSION: Participation in an inclusive aquatics program may lead
      to improved acceptance of children with disabilities by their peers without
      disabilities.

PMID- 22965214
TI  - Commentary on "The psychosocial benefits of an inclusive community-based aquatics
      program".

PMID- 22965215
TI  - Helping the pediatric community understand the importance of observing the effect
      of orthoses.

PMID- 22965216
TI  - Up-regulation of ski-interacting protein in rat brain cortex after traumatic
      brain injury.
AB  - SKIP (Ski-interacting protein), is part of nuclear regulatory complexes and
      interacts with factors involved in preinitiation, splicing and polyadenylation,
      potentiates the activity of important transcription factors, involved in an
      increasing number of signaling cascades. However, its distribution and function
      in the central nervous system remains poorly understood. In this study, western
      blot analysis, RT-PCR and immunohistochemistry showed a significant up-regulation
      of SKIP in ipsilateral peritrauma cortex compared with the sham group.
      Immunofluorescent labeling indicated that SKIP was localized striking in the
      neurons, but not astrocytes and oligodendrocytes; co-localization of SKIP and
      active caspase-3 and PCNA in the ipsilateral cortex. In addition, the expression
      patterns of active caspase-3 and PCNA were parallel with that of SKIP. Based on
      our data, we speculated that SKIP might play an important role in neuronal
      apoptosis following TBI; and might provide a basis for the further study on its
      role in cell cycle re-entry in traumatic brain injury.

PMID- 22965217
TI  - Effect of lycopene and tomato products on cholesterol metabolism.
AB  - BACKGROUND/AIMS: Increased ingestion of tomato, containing lycopene, has been
      associated with a decreased risk for atherosclerosis, although the exact
      molecular mechanism is still unknown. Here we review the available evidence for a
      direct regulation of tomato lycopene on cholesterol metabolism using results from
      experimental and human studies. RESULTS: In human macrophages lycopene dose
      dependently reduced intracellular total cholesterol. Such an effect was
      associated with a decrease in cholesterol synthesis through a reduction of 3
      hydroxy-3-methylglutaryl coenzyme A reductase activity and expression, a
      modulation of low- density lipoprotein (LDL) receptor and acyl-coenzyme
      A:cholesterol acyltransferase activity. An increase in cholesterol efflux through
      an enhancement of ABCA1 and caveolin-1 expression was also observed. In animal
      models of atherosclerosis, lycopene and tomato products decreased plasma total
      cholesterol, LDL cholesterol and increased high-density lipoprotein cholesterol.
      In agreement with the experimental results, most human intervention trials
      analyzed show that dietary supplementation with lycopene and/or tomato products
      reduced plasma LDL cholesterol dependently on the dose and the time of
      administration. CONCLUSIONS: Although lycopene and tomato products seem to
      possess direct hypocholesterolemic properties, more experimental studies are
      needed to better understand the mechanisms involved. There is also a need for
      more well-designed human dietary intervention studies to better clarify the role
      of lycopene as a hypocholesterolemic agent.

PMID- 22965218
TI  - Interobserver and intraobserver reproducibility of hallux valgus angular
      measurements and the study of a linear measurement.
AB  - BACKGROUND: The intermetatarsal angle (IMA), the hallux valgus angle (HVA), and
      the lateral sesamoid malalignment in relation to the first metatarsal are among
      the most commonly employed parameters to estimate the severity of the deformity.
      The aim of this study was to compare HV angular measurements and a linear
      measurement among 4 observers to determine its intraobserver and interobserver
      reliability, to find out whether this linear measurement technique is more
      reproducible than those already-described angular measurements. METHODS: The IMA,
      the HVA, and the distance between the lateral cortex of the first metatarsal and
      the lateral cortex of the lateral sesamoid bone were measured from 50 standing,
      nonoperated hallux valgus feet. Radiographs were shuffled and reforwarded to the
      observers at a minimum interval of 30 days for a new measurement. RESULTS: When
      considering 2 degrees  of difference as significant, IMA and HVA measurements
      were not precise, showing low reproducibility for both intraobserver and
      interobserver assessment. Regarding the distance between the first metatarsal
      lateral cortex and the lateral sesamoid lateral cortex, when considering
      differences greater than 2 mm as significant, we observed higher precision and
      higher reproducibility. CONCLUSIONS: Angular measurements of hallux valgus
      deformity in anteroposterior standing radiographs that are manually performed
      with a goniometer are not precise and have low reproducibility. The linear
      measurement of the distance between the lateral cortices of the first metatarsal
      head and the lateral sesamoid demonstrated higher precision and higher
      reproducibility, and may be a cheap form to assess the correct indication of a
      distal osteotomy. LEVELS OF EVIDENCE: Diagnostic, Level II.

PMID- 22965219
TI  - An incidental finding of an intraosseous metallic object within the os calcis.
AB  - The authors present a case of an incidental finding of a metallic foreign body
      located within the calcaneus of a 17-year-old girl. Although the presence of
      foreign material is a common occurrence in the foot, intraosseous metallic bodies
      are rare, especially so when they present as an incidental finding. A literature
      review of PubMed using keywords metallic, foreign body, and calcaneus revealed
      only a single case report, which did not present as an incidental finding. The
      presentation described here is rare and provides a platform for discussion about
      possible management options.

PMID- 22965220
TI  - Foot orthoses.

PMID- 22965221
TI  - Preoperative hyponatremia and perioperative complications.
AB  - BACKGROUND: Although hyponatremia has been linked to increased morbidity and
      mortality in a variety of medical conditions, its association with perioperative
      outcomes remains uncertain. METHODS: To determine whether preoperative
      hyponatremia is a predictor of 30-day perioperative morbidity and mortality, we
      conducted a cohort study using the American College of Surgeons National Surgical
      Quality Improvement Program database to identify 964 263 adults undergoing major
      surgery from more than 200 hospitals (from January 1, 2005, to December 31, 2010)
      and observed them for 30-day perioperative outcomes. We used multivariable
      logistic regression to estimate relative risks for death, major coronary events,
      wound infections, and pneumonia occurring within 30 days of surgery and quantile
      regression to estimate differences in average length of hospital stay. RESULTS: A
      total of 75 423 patients with preoperative hyponatremia (sodium level <135 mEq/L
      [to convert to millimoles per liter, multiply by 1.0]) were compared with 888 840
      patients with normal baseline sodium levels (135-144 mEq/L). Preoperative
      hyponatremia was associated with a higher risk of 30-day mortality (5.2% vs 1.3%;
      adjusted odds ratio [aOR], 1.44; 95% CI, 1.38-1.50), and this finding was
      consistent in all the subgroups. This association was particularly marked in
      patients undergoing nonemergency surgery (aOR, 1.59; 95% CI, 1.50-1.69; P < .001
      for interaction) and American Society of Anesthesiologists class 1 and 2 patients
      (aOR, 1.93; 95% CI, 1.57-2.36; P < .001 for interaction). Furthermore,
      hyponatremia was associated with a greater risk of perioperative major coronary
      events (1.8% vs 0.7%; aOR, 1.21; 95% CI, 1.14-1.29), wound infections (7.4% vs
      4.6%; 1.24; 1.20-1.28), and pneumonia (3.7% vs 1.5%; 1.17; 1.12-1.22) and
      prolonged median lengths of stay by approximately 1 day. CONCLUSION: Preoperative
      hyponatremia is a prognostic marker for perioperative 30-day morbidity and
      mortality.

PMID- 22965222
TI  - Prevalence of drug interactions in hospital healthcare.
AB  - AIM OF THE REVIEW: To study the prevalence of drug interactions in hospital
      healthcare by reviewing literature. METHOD: A review was carried out of studies
      written in Spanish and English on the prevalence of drug interactions in hospital
      care published in Pubmed between January 1990 and September 2008. The search
      strategy combined free text and MeSH terms, using the following keywords: "Drug
      interaction", "prevalence" and "hospital". For each article, we classified
      independent variables (pathology, age of population, whether patients were
      hospitalized or not, geographical location, etc.) and dependent variables (number
      of interactions per 100 patients studied, prevalence of patients with
      interactions, most common drug interactions, and others). RESULTS: The search
      generated 436 articles. Finally, 47 articles were selected for the study, 3
      provided results about drug interactions with real clinical consequences, 42
      about potential interactions, and 2 described both. The prevalence of patients
      with interactions was between 15 and 45 % and the number of interactions per 100
      patients was between 37 and 106, depending on the group of studies analyzed.
      There was a considerable increase in these rates in patients with heart diseases
      and elderly persons. CONCLUSION: There is a large number of studies on the
      prevalence of drug interactions in hospitals but they report widely varying
      results. The prevalence is higher in patients with heart diseases and elderly
      people.

PMID- 22965223
TI  - The alignment of the knee joint in relationship to age and osteoarthritis: the
      Copenhagen Osteoarthritis Study.
AB  - INTRODUCTION: The aim of the present study was to describe the changes in the
      axis of the knee joint in both radiologically osteoarthritic and non
      osteoarthritic knees, on the basis of angles measurable in standardized clinical
      short knee radiographs, in a cross sectional study of an epidemiological cohort.
      DESIGN: From the third inclusion of the Copenhagen City Heart Study, 4,151
      subjects were selected for standardized radiography of the knees. After censuring
      the inclusion, the resulting cohort was comprised of 3,488 individuals. Images
      were analyzed for radiological knee joint osteoarthritis (OA) and the anatomical
      femorotibial axis of the knee joint was measured. RESULTS: The prevalence of knee
      joint OA in males was 27.9% and 27.5%, for the left and right knees respectively.
      In females this was 32.8% and 36.4%. The mean knee joint angles were 4.11 degrees
      in males; and 5.45 degrees  in females. A difference of 1.3 degrees  was found
      between the genders. In non-osteoarthritic knees the increase in valgus
      orientation in relationship to increasing age was found to be 0.03 degrees  and
      0.04 degrees  per year, respectively, for males and females. Likewise, Kellgren
      and Lawrence found that OA was seen to influence a shift towards varus of 0.55
      degrees -0.76 degrees  per level of OA. CONCLUSION: Stratification in accordance
      with morphological severity of OA documented a clear tendency for the axis of the
      diseased knees to depart from the mean, primarily in the direction of varus. In
      knees exhibiting no signs of radiographic osteoarthritis we found a significant
      relationship between increasing age and a shift in the anatomical axis in the
      direction of valgus.

PMID- 22965224
TI  - Protective effects of VEGF treatment on focal cerebral ischemia in rats.
AB  - The aim of this study was to determine the effects of VEGF treatment on focal
      cerebral ischemia in rats. Rats were administered PBS or VEGF at concentrations
      of 10, 20 or 30 ug/ml. The effects of VEGF on the rat infarct volume and
      neurological deficits were investigated. Transmission electron microscopy was
      used to observe the ultrastructure of the cerebral cortex. Treatments with VEGF
      reduced the infarct volume and improved neurological functions. VEGF increased
      microvessel generation and also inhibited apoptosis in the cerebral cortex and
      basal ganglia. For the rats in the 30 ug/ml VEGF group, an even higher number of
      proliferative endothelial cells were observed by electron microscopy. In
      conclusion, VEGF treatment has protective effects on focal cerebral ischemia in
      rats.

PMID- 22965226
TI  - Characterization of a plasma membrane Ca(2+) ATPase expressed in olfactory
      receptor neurons of the moth Spodoptera littoralis.
AB  - The response of insect olfactory receptor neurons (ORNs) involves an increase in
      intracellular Ca(2+) concentration, as in vertebrate ORNs. In order to decipher
      the Ca(2+) clearance mechanisms in insect ORNs, we have investigated the presence
      of a plasma membrane Ca(2+) ATPase (PMCA) in the peripheral olfactory system of
      the moth Spodoptera littoralis. From an analysis of a male antennal expressed
      sequence-tag database combined with a strategy of 5'/3' rapid amplification of
      cDNA ends plus the polymerase chain reaction, we have cloned a full-length cDNA
      encoding a PMCA. In adult males, the PMCA transcript has been found in various
      tissues, including the antennae in which its presence has been detected in the
      sensilla trichodea, and in cultured ORNs. The PMCA gene is slightly expressed at
      the end of the pupal stage, reaches a maximum at emergence and is maintained at a
      high level during the adult period. Taken together, these results provide, for
      the first time, molecular evidence for the putative participation of a PMCA in
      signalling pathways responsible for the establishment and functioning of the
      insect peripheral olfactory system.

PMID- 22965225
TI  - Interstitial cystitis and the overlap with overactive bladder.
AB  - The overlap between interstitial cystitis-painful bladder syndrome and overactive
      bladder can present a diagnostic challenge to the treating practitioner. Both can
      present with similar patient symptoms. Further compounding this dilemma is the
      fact that no gold standard test exists to differentiate one from the other. This
      review will serve to highlight their similarities and distinguishing features.

PMID- 22965227
TI  - Another rare case of a child with de novo terminal 9p deletion and co-existing
      interstitial 9p duplication: clinical findings and molecular cytogenetic study by
      array-CGH.
AB  - Trisomy 9p is the fourth most common chromosome abnormality found in liveborns.
      We report on a rare case of partial trisomy 9p complicated by partial monosomy
      9p. Clinical manifestation included craniofacial abnormalities typical for
      trisomy 9p syndrome, developmental delay, mental retardation and brain anomaly in
      the form of Dandy-Walker malformation. The cytogenetic abnormality was
      investigated with FISH and array-CGH to characterize the breakpoints of the
      complex rearrangement. The patient's karyotype was
      46,XX,der(9)del(9)(p24)dup(9)(p21p24)dn.arr 9p24.3p24.2 (1
      2,414,485)*1,9p24.2p21.3(2,414,485-24,101,280)*3. The cytogenetic rearrangement
      led to a 2.4-Mb deletion of 9p24.2pter and a 21.6-Mb duplication of 9p24.2p21.3.
      The clinical and cytogenetic findings in our and other similar patients are
      compared.

PMID- 22965228
TI  - Cyclin-dependent kinase-1 (Cdk1)/cyclin B1 dictates cell fate after mitotic
      arrest via phosphoregulation of antiapoptotic Bcl-2 proteins.
AB  - The prevailing model suggests that cell fate after mitotic arrest depends on two
      independent and competing networks that control cyclin B1 degradation and the
      generation of death signals. However, recent evidence for Cdk1/cyclin B1-mediated
      phosphorylation and inactivation of antiapoptotic Bcl-2 proteins suggests the
      existence of significant cross-talk and interdependence between these pathways.
      Further, the nature of the mitotic death signals has remained elusive. In this
      study, we sought to test the hypothesis that fate after mitotic arrest is
      dictated by the robustness of Cdk1/cyclin B1 signaling to Bcl-2 proteins and to
      identify signals that may represent a mitotic death signature. We show that when
      treated with Taxol, slippage-resistant HT29 colon carcinoma cells display robust
      Cdk1 activity and extensive Mcl-1/Bcl-x(L) phosphorylation and die in mitosis,
      whereas slippage-prone DLD-1 colon carcinoma cells display weak Cdk1 activity and
      partial and transient Mcl-1/Bcl-x(L) phosphorylation and die in subsequent
      interphase or survive. Furthermore, modulation of this signaling axis, either by
      inhibition of Cdk1 in slippage-resistant HT29 or by enforcing mitotic arrest in
      slippage-prone DLD-1 cells, evokes a switch in fate, indicating that the strength
      of Cdk1 signaling to Bcl-2 proteins is a key determinant of outcome. These
      findings provide novel insight into the pathways that regulate mitotic death,
      suggest that the robustness of these signaling events may be useful as a marker
      to define susceptibility to antimitotic drugs, and encourage a revision in the
      current model describing fate after mitotic arrest.

PMID- 22965229
TI  - A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare
      inherited polyagglutination syndrome.
AB  - Rare polyagglutinable NOR erythrocytes contain three unique globoside (Gb4Cer)
      derivatives, NOR1, NOR(int), and NOR2, in which Gal(alpha1-4), GalNAc(beta1
      3)Gal(alpha1-4), and Gal(alpha1-4)GalNAc(beta1-3)Gal(alpha1-4), respectively, are
      linked to the terminal GalNAc residue of Gb4Cer. NOR1 and NOR2, which both
      terminate with a Gal(alpha1-4)GalNAc- sequence, react with anti-NOR antibodies
      commonly present in human sera. While searching for an enzyme responsible for the
      biosynthesis of Gal(alpha1-4)GalNAc, we identified a mutation in the A4GALT gene
      encoding Gb3/CD77 synthase (alpha1,4-galactosyltransferase). Fourteen NOR
      positive donors were heterozygous for the C>G mutation at position 631 of the
      open reading frame of the A4GALT gene, whereas 495 NOR-negative donors were
      homozygous for C at this position. The enzyme encoded by the mutated gene
      contains glutamic acid instead of glutamine at position 211 (substitution Q211E).
      To determine whether this mutation could change the enzyme specificity, we
      transfected a teratocarcinoma cell line (2102Ep) with vectors encoding the
      consensus Gb3/CD77 synthase and Gb3/CD77 synthase with Glu at position 211. The
      cellular glycolipids produced by these cells were analyzed by flow cytometry,
      high-performance thin-layer chromatography, enzymatic degradation, and MALDI-TOF
      mass spectrometry. Cells transfected with either vector expressed the P1 blood
      group antigen, which was absent from untransfected cells. Cells transfected with
      the vector encoding the Gb3/CD77 synthase with Glu at position 211 expressed both
      P1 and NOR antigens. Collectively, these results suggest that the C631G mutation
      alters the acceptor specificity of Gb3/CD77 synthase, rendering it able to
      catalyze synthesis of the Gal(alpha1-4)Gal and Gal(alpha1-4)GalNAc moieties.

PMID- 22965230
TI  - High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease
      refractory to common resistant mutants.
AB  - Hepatitis C virus (HCV) NS3-4A protease is essential for viral replication. All
      current small molecular weight drugs against NS3-4A are substrate peptidomimetics
      that have a similar binding and resistance profile. We developed inhibitory
      peptides (IPs) capping the active site and binding via a novel "tyrosine" finger
      at an alternative NS3-4A site that is of particular interest for further HCV drug
      development. The peptides are not cleaved due to a combination of geometrical
      constraints and impairment of the oxyanion hole function. Selection and
      optimization through combinatorial phagemid display, protein crystallography, and
      further modifications resulted in a 32-amino acid peptide with a K(i) of 0.53 nm.
      Inhibition of viral replication in cell culture was demonstrated by fusion to a
      cell-penetrating peptide. Negligible susceptibility to known (A156V and R155K)
      resistance mutations of the NS3-4A protease was observed. This work shows for the
      first time that antiviral peptides can target an intracellular site and reveals a
      novel druggable site on the HCV protease.

PMID- 22965231
TI  - The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl
      carrier protein, an essential step in biotin synthesis.
AB  - Recent work implicated the Escherichia coli BioC protein as the initiator of the
      synthetic pathway that forms the pimeloyl moiety of biotin (Lin, S., Hanson, R.
      E., and Cronan, J. E. (2010) Nat. Chem. Biol. 6, 682-688). BioC was believed to
      be an O-methyltransferase that methylated the free carboxyl of either malonyl-CoA
      or malonyl-acyl carrier protein based on the ability of O-methylated (but not
      unmethylated) precursors to bypass the BioC requirement for biotin synthesis both
      in vivo and in vitro. However, only indirect proof of the hypothesized enzymatic
      activity was obtained because the activities of the available BioC preparations
      were too low for direct enzymatic assay. Because E. coli BioC protein was
      extremely recalcitrant to purification in an active form, BioC homologues of
      other bacteria were tested. We report that the native form of Bacillus cereus
      ATCC10987 BioC functionally replaced E. coli BioC in vivo, and the protein could
      be expressed in soluble form and purified to homogeneity. In disagreement with
      prior scenarios that favored malonyl-CoA as the methyl acceptor, malonyl-acyl
      carrier protein was a far better acceptor of methyl groups from S-adenosyl-L
      methionine than was malonyl-CoA. BioC was specific for the malonyl moiety and was
      inhibited by S-adenosyl-L-homocysteine and sinefungin. High level expression of
      B. cereus BioC in E. coli blocked cell growth and fatty acid synthesis.

PMID- 22965232
TI  - Stimulus bias provides evidence for conformational constraints in the structure
      of a G protein-coupled receptor.
AB  - A key characteristic of G protein-coupled receptors (GPCRs) is that they activate
      a plethora of signaling pathways. It is now clear that a GPCR coupling to these
      pathways can be regulated selectively by ligands that differentially drive
      signaling down one pathway in preference to another. This concept, termed
      stimulus bias, is revolutionizing receptor biology and drug discovery by
      providing a means of selectively targeting receptor signaling pathways that have
      therapeutic impact. Herein, we utilized a novel quantitative method that
      determines stimulus bias of synthetic GPCR ligands in a manner that nullifies the
      impact of both the cellular background and the "natural bias" of the endogenous
      ligand. By applying this method to the M(2) muscarinic acetylcholine receptor, a
      prototypical GPCR, we found that mutation of key residues (Tyr-80(2.61) and Trp
      99(3.28)) in an allosteric binding pocket introduces stimulus bias in response to
      the atypical ligands AC-42 (4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1
      butyl)piperidine HCl) and 77-LH-28-1 (1-(3-(4-butyl-1-piperidinyl)propyl)- 3,3
      dihydro-2(1H)-quinolinone). By comparing stimulus bias factors among receptor
      internalization, G protein activation, extracellular-regulated protein kinase 1/2
      (ERK1/2) signaling, and receptor phosphorylation, we provide evidence that Tyr
      80(2.61) and Trp-99(3.28) act either as molecular switches or as gatekeeper
      residues that introduce constraints limiting the active conformation of the M(2)
      muscarinic acetylcholine receptor and thereby regulate stimulus bias.
      Furthermore, we provide evidence that downstream signaling pathways previously
      considered to be related to each other (i.e. receptor phosphorylation,
      internalization, and activation of ERK1/2) can act independently.

PMID- 22965234
TI  - Welcome to Kunming!

PMID- 22965233
TI  - Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other
      tissue defects with impaired nuclear pore function in zebrafish embryos.
AB  - The Nup107-160 multiprotein subcomplex is essential for the assembly of nuclear
      pore complexes. The developmental functions of individual constituents of this
      subcomplex in vertebrates remain elusive. In particular, it is unknown whether
      Nup107 plays an important role in development of vertebrate embryos. Zebrafish
      nup107 is maternally expressed and its zygotic expression becomes prominent in
      the head region and the intestine from 24 h postfertilization (hpf) onward. In
      this study, we generate a zebrafish mutant line, nup107(tsu068Gt), in which the
      nup107 locus is disrupted by an insertion of Tol2 transposon element in the first
      intron and as a result it fails to produce normal transcripts. Homozygous
      nup107(tsu068Gt) mutant embryos exhibit tissue-specific defects after 3 days
      postfertilization (dpf), including loss of the pharyngeal skeletons, degeneration
      of the intestine, absence of the swim bladder, and smaller eyes. These mutants
      die at 5-6 days. Extensive apoptosis occurs in the affected tissues, which is
      partially dependent on p53 apoptotic pathways. In cells of the defective tissues,
      FG-repeat nucleoporins are disturbed and nuclear pore number is reduced, leading
      to impaired translocation of mRNAs from the nucleus to the cytoplasm. Our
      findings shed new light on developmental function of Nup107 in vertebrates.

PMID- 22965235
TI  - Bovine versus porcine acellular dermal matrix for complex abdominal wall
      reconstruction.
AB  - BACKGROUND: Abdominal wall reconstruction with bioprosthetic mesh is associated
      with lower rates of mesh infection, fistula formation, and mesh explantation than
      reconstruction with synthetic mesh. The authors directly compared commonly used
      bioprosthetic meshes in terms of clinical outcomes and complications. METHODS: A
      database of consecutive patients who underwent abdominal wall reconstruction with
      porcine or bovine acellular dermal matrix and midline musculofascial closure at
      their institution between January of 2008 and March of 2011 was reviewed.
      Surgical outcomes were compared. RESULTS: One hundred twenty patients were
      identified who underwent a nonbridged, inlay abdominal wall reconstruction with
      porcine [69 patients (57.5 percent)] or bovine acellular dermal matrix (51
      patients (42.5 percent)]. The mean follow-up time was 21.0 +/- 9.9 months. The
      overall complication rate was 36.6 percent; the porcine matrix group had a
      significantly higher complication rate (44.9 percent) than the bovine matrix
      group (25.5 percent; p = 0.04) and statistically equivalent surgical
      complications (29.2 percent versus 21.6 percent; p = 0.34). There were no
      significant differences in rates of recurrent hernia (2.9 percent versus 3.9
      percent; p = 0.99) or bulge (7.2 percent versus 0 percent; p = 0.07). However,
      the rate of intraoperative adverse events in the porcine matrix group [seven
      events (10.1 percent)] was significantly higher than that in the bovine matrix
      group (0 percent; p = 0.02). CONCLUSIONS: In patients who undergo complex
      abdominal wall reconstruction, both bovine and porcine acellular dermal matrix
      are associated with similar rates of postoperative surgical complications and
      appear to result in similar outcomes. Porcine acellular dermal matrix may be
      prone to intraoperative device failure. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 22965236
TI  - Treatment and outcomes of fingertip injuries at a large metropolitan public
      hospital.
AB  - BACKGROUND: Fingertip injuries are the most common hand injuries presenting for
      acute care. Treatment algorithms have been described based on defect size, bone
      exposure, and injury geometry. The authors hypothesized that despite accepted
      algorithms, many fingertip injuries can be treated conservatively. METHODS: A
      prospectively collected retrospective review of all fingertip injuries presenting
      to Bellevue Hospital between January and May of 2011 was conducted. Patients were
      entered into an electronic database on presentation. Follow-up care was tracked
      through the electronic medical record. Patients lost to follow-up were questioned
      by means of telephone. Patients were analyzed based on age, mechanism of injury,
      handedness, occupation, wound geometry, defect size, bone exposure, emergency
      room procedures performed, need for surgical intervention, and outcome. RESULTS:
      One hundred fingertips were injured. Injuries occurred by crush (46 percent),
      laceration (30 percent), and avulsion (24 percent). Sixty-four percent of
      patients healed without surgery, 18 percent required operative intervention, and
      18 percent were lost to follow-up. Patients requiring operative intervention were
      more likely to have a larger defect (3.28 cm versus 1.75 cm, p < 0.005), volar
      oblique injury (50 percent versus 8.8 percent, p < 0.005), exposed bone (81.3
      percent versus 35.3 percent, p < 0.005), and an associated distal phalanx
      fracture (81.3 percent versus 47.1 percent, p < 0.05). Patients requiring
      surgical intervention had a longer average return to work time when compared with
      those not requiring surgical intervention (4.33 weeks versus 2.98 weeks, p <
      0.001). CONCLUSION: Despite current accepted algorithms, many fingertip injuries
      can be treated nonoperatively to achieve optimal sensation, fine motor control,
      and earlier return to work. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 22965237
TI  - Bilateral orbital dysmorphology in unicoronal synostosis.
AB  - BACKGROUND: Orbital dysmorphology is believed to cause ipsilateral ocular
      abnormalities in unicoronal synostosis. Recently, there has been increasing
      evidence of visual problems in the contralateral eye. The purpose of this study
      was to explore morphology of both the ipsilateral and contralateral unicoronal
      synostosis orbit. METHODS: Demographic data and computed tomographic information
      were recorded. Three-dimensional computed tomographic renderings were created
      digitally and analyzed (SurgiCase). Craniometric analysis was conducted for
      orbital volume, horizontal and vertical orbital cone angle, orbital depth, and
      corneal projection. RESULTS: Twenty-one unicoronal synostosis infants and 10
      matched controls were examined. The orbital volume ratio between ipsilateral and
      contralateral sides was 93.8 +/- 5.3 in unicoronal synostosis infants and 99.3 +/
      2.1 (p = 0.001) in the control group. The horizontal orbital cone angle of the
      contralateral eye was significantly greater than that of both the ipsilateral
      side (p < 0.0001) and the control orbits (p = 0.0011, p = 0.0004). The vertical
      cone angle of the ipsilateral eye was significantly greater than that of the
      ipsilateral (p < 0.0001) and control orbits (p = 0.0326, p = 0.0030). There was
      no difference in orbital depth between ipsilateral and contralateral orbits. The
      ipsilateral globe projected 27 percent farther past the orbital aperture than the
      contralateral side. There was no difference between right and left orbits of a
      control in any analysis. CONCLUSIONS: In addition to ipsilateral orbital
      deformity, the contralateral orbit is highly dysmorphic. As orbital asymmetry may
      underlie visual abnormalities, future reconstructive efforts may necessitate
      bilateral correction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 22965238
TI  - Simultaneous augmentation/mastopexy:  a retrospective 5-year review of 332
      consecutive cases.
AB  - BACKGROUND: Of all mastopexies performed in the authors' facility, approximately
      77 percent of patients have an implant placed simultaneously. The unique
      challenges and safety concerns associated with the simultaneous
      augmentation/mastopexy procedure merit a deeper evaluation of its use and
      associated risks. METHODS: A retrospective analysis of 430 mastopexy operations,
      including 332 simultaneous augmentation mastopexies, was performed. Patient
      demographics, patient selection, and operative approach were evaluated and
      correlated with surgical outcomes. Complications and reoperation rates were
      measured and compared with published reports in the literature. RESULTS: For
      simultaneous augmentation/mastopexy procedures, the overall complication rate was
      22.9 percent (primary cases, 20.4 percent; secondary cases, 28.9 percent). Tissue
      and implant-related complication rates were 15.1 and 7.8 percent, respectively.
      The overall reoperation rate was 23.2 percent (primary cases, 20.0 percent;
      secondary cases, 30.9 percent). Tissue- and implant-related reoperation rates
      were 13.3 and 9.9 percent, respectively. The most common complications were
      capsular contracture (13 of 332), poor scarring (11 of 332), and recurrent ptosis
      (11 of 332). They were also the most common indications for reoperation (11 of
      332 for each one). The mastopexy-only reoperation rate of 10.2 percent was
      comparable to the tissue-related reoperation rate of 13.3 percent. CONCLUSIONS:
      Although the measured reoperation rate (23.2 percent) may be higher than that of
      either procedure performed independently, the revision rate of combining the
      procedures was not more than additive. With appropriate patient selection and a
      carefully planned operative approach, the authors believe a one-stage procedure
      can be safely performed with acceptable complication and reoperation rates.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 22965239
TI  - A systematic review of antibiotic use and infection in breast reconstruction: 
      what is the evidence?
AB  - BACKGROUND: The literature reports overall complication rates in breast
      reconstruction to be as high as 60 percent. Infection rates can exceed 20
      percent, much higher than anticipated in clean elective surgery. There is no
      consensus among surgeons regarding the necessary duration of antibiotic
      prophylaxis, although the Centers for Disease Control and Prevention guidelines
      suggest only 24 hours. This systematic review examines antibiotic regimens and
      associated infection rates in breast reconstruction. METHODS: Systematic
      electronic searches were performed in the PubMed, Ovid, and Cochrane databases
      using Medical Subject Headings terms for studies reporting antibiotic use and
      infection in all forms of breast reconstruction. Studies between 1970 and 2011
      were reviewed. Included publications were required to report an antibiotic
      protocol and infection rate. RESULTS: A total of 834 abstracts were identified,
      81 of which met inclusion criteria and were included in the review. The overall
      reported infection rates in the included studies varied between 0 and 29 percent
      (average, 5.8 percent). When comparing combined patient cohorts receiving no
      antibiotics, less than 24 hours, and greater than 24 hours, the average infection
      rates were 14.4, 5.8, and 5.8 percent, respectively. CONCLUSIONS: There is no
      consensus on the necessary duration of antibiotic prophylaxis following breast
      reconstruction. No benefit was found in patients who received more than 24 hours
      of postoperative antibiotics. Standardized definitions for antibiotic regimens,
      unit of analysis reporting, and a new breast reconstruction surgical-site
      infection grading system are offered to improve standardized outcome
      documentation. Randomized controlled trials are warranted to best determine an
      optimal antibiotic regimen. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 22965240
TI  - The effect of age on human adipose-derived stem cells.
AB  - BACKGROUND: Adipose-derived mesenchymal stem cells are a robust, multipotent cell
      source. They are easily harvested and exhibit promise in a variety of
      regenerative applications. The purpose of this study was to evaluate the aging
      impact on adipose-derived mesenchymal stem cells, relating to morphology,
      senescent properties, growth factor expression, and osteogenesis. METHODS: Cells
      obtained from distinct age groups (infant, adult, and elderly) were cultured.
      Morphology was examined using microscopy, and cell surface markers were
      interrogated using flow cytometry. Telomere length was measured using real-time
      polymerase chain reaction. Expression of pertinent angiogenic and osteogenic
      growth factors was compared. Osteogenic capability was investigated further by
      evaluating induction response, and by quantification of mRNA expression of RUNX-2
      and osteocalcin. RESULTS: The same isolating ratio of mesenchymal stem cells was
      derived from each donor, regardless of age. The infant adipose-derived stem cells
      exhibited elongated spindle morphology and increased telomere length compared
      with older cells. Angiogenic factors were more highly expressed by infant cells,
      whereas osteogenic expression was similar among all ages. Response to osteogenic
      induction was more profound in infant than in older stem cells, as evidenced by
      alkaline phosphatase and alizarin red staining, as was bone-related gene
      expression. CONCLUSIONS: Adipose-derived mesenchymal stem cells are available
      across all age groups. Infant-derived cells are morphologically spindle-shaped,
      with long telomeres, and exhibit enhanced angiogenic and osteogenic capabilities
      compared with older cells. Conversely, all age groups exhibit similar osteogenic
      paracrine activity, and the authors posit that clinical applicability is
      conserved during the adult to elderly period.

PMID- 22965241
TI  - A comprehensive algorithm for oncologic maxillary reconstruction.
AB  - BACKGROUND: Management of maxillary defects is among the most challenging and
      controversial areas of head and neck reconstruction. The authors develop a
      treatment algorithm based on outcomes following free flap reconstruction of
      various maxillary defects. METHODS: A review of 246 maxillary free flap
      reconstructions was performed. RESULTS: The authors' analysis demonstrated that
      the palatoalveolar resection predicted use of soft-tissue (n = 200) versus
      osteocutaneous (n = 46) free flaps, depending on the location and extent of the
      defect. Whether the orbital floor or the entire orbital contents were resected
      also had implications for flap choice and whether bone grafts or alloplasts were
      needed. The perioperative complication rate was 37.8 percent, including a 3.3
      percent incidence of flap loss. The long-term complication rate was 12.1 percent,
      including a 7.5 percent fistula rate. Complications related to orbital floor
      reconstruction were not dependent on the material used (p = 0.18). Greater than
      80 percent speech intelligibility was achieved by 95.1 percent of patients, and
      90.6 percent tolerated an unrestricted or soft diet. CONCLUSIONS: To restore both
      midfacial form and function, the palatoalveolar defect and the status of the
      orbital floor and orbital contents must be addressed. Defects that involve the
      anterior maxilla should be addressed with osteocutaneous free flaps if possible,
      and posterior defects can often be reconstructed with soft-tissue free flaps. The
      orbital floor requires rigid reconstruction, with either bone grafts or
      alloplasts, unless the orbital contents have also been exenterated, in which case
      a soft-tissue free flap should be used to close the orbital cavity.

PMID- 22965243
TI  - Facing the challenges for Europe--research into action: Liverpool European
      Congress of Obesity, May 12-15, 2013.

PMID- 22965242
TI  - The biological activity of auranofin: implications for novel treatment of
      diseases.
AB  - More than 30 years ago, auranofin was developed for the treatment of rheumatoid
      arthritis as a substitution for the injectable gold compounds aurothiomalate and
      aurothioglucose. Both the ease of oral administration over intramuscular
      injections and more potent anti-inflammatory effects in vitro made auranofin seem
      like an excellent substitute for the traditional injectable gold compounds.
      Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis,
      currently, auranofin is seldom used as a treatment for patients with rheumatoid
      arthritis as more novel anti-rheumatic medications have become available. Despite
      the decline in its clinical applications, research on auranofin has continued as
      it shows promise in the treatment of several different diseases. In recent years,
      advances in technology have allowed researchers to use molecular techniques to
      identify novel mechanisms of action of auranofin. Additionally, researchers are
      discovering potential new applications of auranofin. Dual inhibition of
      inflammatory pathways and thiol redox enzymes by auranofin makes it a new
      candidate for cancer therapy and treating microbial infections. This review will
      summarize recently obtained data on the mechanisms of action of auranofin, and
      potential new applications of auranofin in the treatment of various diseases,
      including several types of leukaemia, carcinomas, and parasitic, bacterial, and
      viral infections.

PMID- 22965244
TI  - Local hemodynamics at the rupture point of cerebral aneurysms determined by
      computational fluid dynamics analysis.
AB  - BACKGROUND: Cerebral aneurysms carry a high risk of rupture and so present a
      major threat to the patient's life. Accurate criteria for predicting aneurysm
      rupture are important for therapeutic decision-making, and some clinical and
      morphological factors may help to predict the risk for rupture of unruptured
      aneurysms, such as sex, size and location. Hemodynamic forces are considered to
      be key in the natural history of cerebral aneurysms, but the effect on aneurysm
      rupture is uncertain, and whether low or high wall shear stress (WSS) is the most
      critical in promoting rupture remains extremely controversial. This study
      investigated the local hemodynamic features at the aneurysm rupture point.
      METHODS: Computational models of 6 ruptured middle cerebral artery aneurysms with
      intraoperative confirmation of rupture point were constructed from 3-dimensional
      rotational angiography images. Computational fluid dynamics (CFD) simulations
      were performed under pulsatile flows using patient-specific inlet flow
      conditions. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were
      calculated, and compared at the rupture point and at the aneurysm wall without
      the rupture point. We performed an additional CFD simulation of a bleb-removed
      model for a peculiar case in which bleb formation could be confirmed by magnetic
      resonance angiography. RESULTS: All rupture points were located at the body or
      dome of the aneurysm. The TAWSS at the rupture point was significantly lower than
      that at the aneurysm wall without the rupture point (1.10 vs. 4.96 Pa, p =
      0.031). The OSI at the rupture point tended to be higher than at the aneurysm
      wall without the rupture point, although the difference was not significant
      (0.0148 vs. 0.0059, p = 0.156). In a bleb-removed simulation, the TAWSS at the
      bleb-removed area was 6.31 Pa, which was relatively higher than at the aneurysm
      wall (1.94 Pa). CONCLUSION: The hemodynamics of 6 ruptured cerebral aneurysms of
      the middle cerebral artery were examined using retrospective CFD analysis. We
      could confirm the rupture points in all cases. With those findings, local
      hemodynamics of ruptured aneurysms were quanti-tatively investigated. The rupture
      point is located in a low WSS region of the aneurysm wall. Bleb-removed
      simulation showed increased WSS of the bleb-removed area, associated with the
      flow impaction area. Although the number of subjects in this study was relatively
      small, our findings suggest that the location of the rupture point is related to
      a low WSS at the aneurysm wall. Further investigations will elucidate the
      detailed hemodynamic effects on aneurysm rupture.

PMID- 22965246
TI  - Increase screening for hepatitis B among Asians.

PMID- 22965247
TI  - Diagnosis of infection in the diabetic foot using (18)F-FDG PET/CT: a sweet
      alternative?

PMID- 22965248
TI  - Is chronic nipple piercing associated with hyperprolactinemia?
AB  - Literature on hyperprolactinemia in the setting of a nipple piercing is limited
      to individuals with concomitant breast/chest wall infection. It is unclear if
      chronic nipple stimulation from a piercing alone can cause sustained elevations
      of serum prolactin. Nipple piercing is emerging as a more mainstream societal
      form of body art, and the answer to this clinical question would potentially
      alter patient management. Our aim was to assess serum prolactin levels in
      subjects with nipple piercing. Inclusion criteria were as follows: men and women
      >= 18 years old with nipple piercing(s) present > 6 months. Exclusion criteria
      included: women who are pregnant, lactating or < 6 months postpartum; subjects on
      medications known to increase prolactin levels; chest wall/breast infection at
      the time of phlebotomy or conditions known to be associated with
      hyperprolactinemia. Three men and eight women were enrolled. Median (range) ages
      for men and women were 33 (24-42) and 27 years (23-42), respectively. All except
      one subject had bilateral piercings. The median interval from nipple piercing to
      blood draw was 4.0 (2.0-12.0) years. None of the subjects had hyperprolactinemia.
      Median (range) prolactin levels for men and women were 5.6 ng/mL (3.8-7.4) and
      8.0 ng/mL (2.8-10.9), respectively. Our results suggest that in the absence of
      any concomitant infection, chronic nipple piercing is not associated with
      hyperprolactinemia.

PMID- 22965249
TI  - Glucose-regulated protein 75 overexpression attenuates ionizing radiation
      mediated injury in PC12 cells by inducing the expression of topoisomerase
      IIalpha.
AB  - Glucose-regulated protein 75 (Grp75), also known as mortalin/mthsp70/PBP74, is a
      member of the heat-shock protein 70 (HSP70) family. Grp75 is known to protect
      cells from stress-induced injury. Previous studies have shown that the expression
      of Grp75 is upregulated by a low dose of ionizing radiation (IR). To evaluate the
      protective role of Grp75 on cell proliferation in response to IR, Grp75 was
      overexpressed in a rat adrenal pheochromocytoma cell line (PC12). It was revealed
      that Grp75 overexpression desensitized PC12 cells to IR-mediated cell injury. In
      addition, the expression of topoisomerase IIalpha (Topo IIalpha) was
      downregulated in PC12 cells following gamma-ray IR. The effect of Grp75
      overexpression on Topo IIalpha expression was examined. It was revealed that
      Grp75 overexpression reversed the inhibitory effect of IR on Topo IIalpha
      expression. In conclusion, the data indicated that Grp75 overexpression
      attenuates IR-induced injury in PC12 cells by maintaining the expression of Topo
      IIalpha.

PMID- 22965258
TI  - Validation of the Korean version of the Oxford Knee Score in patients undergoing
      total knee arthroplasty.
AB  - BACKGROUND: Although translated versions of the Oxford Knee Score (OKS) in
      several languages are available, the absence of a Korean version precludes
      comparing data from Korea with that from other countries using the OKS.
      QUESTIONS/PURPOSES: We therefore evaluated the reliability and validity of the
      adapted Korean version of the OKS. METHODS: We first translated the English
      version of the OKS into Korean, then back into English, then held expert
      committee discussions to finalize the Korean version. We then mailed the Korean
      version of the VAS for pain, OKS, and the previously validated SF-36 to 142
      patients who underwent TKAs for knee osteoarthritis. Factor analysis and
      reliability assessment using the kappa statistic of agreement for each item, the
      intraclass correlation coefficient, and Cronbach's alpha were conducted. To
      determine the subscales of the OKS, we used the factor analysis. We also
      evaluated concurrent and construct validity by comparing the responses to the OKS
      with the results of the VAS and SF-36 using Pearson's correlation coefficient.
      RESULTS: All items had a kappa statistic of agreement greater than 0.6. The OKS
      showed test and retest reliability as follows: OKS, 0.848; Factor 1, 0.867; and
      Factor 2, 0.819. Internal consistency of Cronbach's alpha was as follows: OKS,
      0.932; Factor 1, 0.907; Factor 2, 0.867. The OKS correlated (r = 0.692) with the
      VAS. The Korean version of the OKS correlated with the SF-36 total and individual
      domain (physical functioning, role physical, bodily pain) scores. CONCLUSIONS:
      The adapted Korean version of the OKS was translated and showed acceptable
      measurement properties. The data suggest it is suitable for assessing outcomes in
      Korean-speaking patients having TKAs.

PMID- 22965259
TI  - Childhood obesity as a risk factor for lateral condyle fractures over
      supracondylar humerus fractures.
AB  - BACKGROUND: Obese children reportedly have an increased risk of sustaining
      musculoskeletal injuries compared with their normal-weight peers. Obese children
      are at greater risk for sustaining fractures of the forearm, particularly from
      low-energy mechanisms. Furthermore, obesity is a risk factor for sustaining an
      extremity fracture requiring surgery. However, it is unclear what role obesity
      plays in fractures about the distal humerus. QUESTIONS/PURPOSES: We therefore
      asked whether (1) children who sustain lateral condyle (LC) fractures have a
      higher body mass index (BMI) as compared with those with supracondylar (SC)
      humerus fractures; and (2) children with a higher BMI sustain more severe
      fractures regardless of fracture pattern. METHODS: We retrospectively reviewed
      992 patients: 230 with LC injuries and 762 with SC fractures. We determined BMI
      and BMI-for-age percentiles. Fracture types were classified by the systems
      proposed by Weiss et al. (LC fractures) and Wilkins (SC fractures). RESULTS: The
      LC group had both a higher mean BMI and BMI-for-age percentile than the SC group
      as well as had more obese patients (37% versus 19%). Within the LC group,
      children with Type 3 fractures had a higher BMI that those with Type 1 fractures
      (19 versus 17). There was a higher percentage of obese patients with Type 3 LC
      fractures compared with Type 1 and 2 fractures (44% versus 27% and 26%). Among
      patients with SC fractures, there was no difference among the BMI, BMI-for-age
      percentiles, or percentage of obese children when analyzed by fracture subtype.
      CONCLUSIONS: Obesity places a child at greater risk for sustaining a LC fracture
      and when these fractures occur, they are often more severe injuries compared with
      those in nonobese children. LEVEL OF EVIDENCE: Level II, prognostic study. See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 22965260
TI  - Cross-sectional anatomy of the ilium: implications for acetabular component
      placement in total hip arthroplasty.
AB  - BACKGROUND: High hip center reconstructions, used in revision and complex primary
      THAs, rely on pelvic bone stock at least 35 mm above the anatomic teardrop.
      However, the technique does not restore normal hip biomechanics and controversy
      exists regarding acetabular implant survival. Previous reports document a wide
      range of implant positioning above the teardrop. There is no anatomic guidance in
      the literature regarding the amount of bone stock available for initial implant
      stability in this area of the ilium. QUESTIONS/PURPOSES: We therefore determined
      the thickness of the human ilium and related it to acetabulum cup coverage in
      high hip center reconstructions. METHODS: We sectioned 16 cadaveric hips from the
      anterior superior iliac spine to the anatomic teardrop in 5-mm increments, then
      measured the thickness of the ilium for each cross section. RESULTS: The maximum
      thickness of 42 +/- 9 mm occurred at the dome of the acetabulum 35 +/- 3 mm above
      the teardrop. At a distance of 1 cm above the dome, the ilium was reduced by 24%,
      to 32 +/- 6 mm. At 2 cm above the dome, the ilium thickness was 22 +/- 4 mm, a
      48% reduction from its maximum. CONCLUSION: There are substantial anatomic
      limitations to high hip reconstructions 2 cm above the acetabular dome.

PMID- 22965262
TI  - Is posterior synovial plica excision necessary for refractory lateral
      epicondylitis of the elbow?
AB  - BACKGROUND: Arthroscopic treatments for lateral epicondylitis including
      debridement of the extensor carpi radialis brevis (ECRB) origin (Baker technique)
      or resection of the radiocapitellar synovial plica reportedly improve symptoms.
      However the etiology of the disease and the role of the plica remain unclear.
      QUESTIONS/PURPOSES: We asked if posterior radiocapitellar synovial plica excision
      made any additional improvement in pain or function after arthroscopic ECRB
      release. METHODS: We retrospectively reviewed 38 patients who had arthroscopic
      treatment for refractory lateral epicondylitis between November 2003 and October
      2009. Twenty patients (Group A) underwent the Baker technique and 18 patients
      (Group B) underwent a combination of the Baker technique and posterior synovial
      plica excision. The minimum followup was 36 months (mean, 46 months; range, 36-72
      months) for Group A and 25 months (mean, 30 months; range, 25-36 months) for
      Group B. Postoperatively we obtained VAS pain and DASH scores for each group.
      RESULTS: Two years postoperatively, we found no differences in the VAS pain score
      or DASH: the mean VAS pain scores were 0.3 points in Group A and 0.4 points in
      Group B, and the DASH scores were 5.1 points and 6.1 points respectively.
      CONCLUSIONS: The addition of debridement of the posterior synovial fold did not
      appear to enhance either pain relief or function compared with the classic Baker
      technique without decortication.

PMID- 22965263
TI  - Early posttransplantation hyperglycemia in kidney transplant recipients is
      associated with overall long-term graft losses.
AB  - BACKGROUND: The association of early-onset posttransplantation hyperglycemia with
      long-term renal allograft survival is unknown. METHODS: Seventy-one (SD 9) days
      after transplantation, 1410 first-time kidney transplant recipients without
      diabetes underwent an oral glucose tolerance test and were observed until primary
      outcome (graft loss) or December 31, 2008 (median [range], 6.0 years [0.3-13.8
      years]). We used multivariable Cox regression analysis adjusted for age, gender,
      body mass index, creatinine level, donor age, preemptive transplantation,
      deceased donor, early rejection, and early cytomegalovirus infection to estimate
      hazard ratios for overall and death-censored allograft survival. RESULTS: A total
      of 392 (28%) recipients experienced graft failure, and 235 (60%) were induced by
      death. Each 1 mmol/L increase in 2-hr plasma glucose (2hPG) was associated with
      7% and 3% increased risk of unadjusted and adjusted overall graft failure (hazard
      ratio [95% confidence interval], 1.07 [1.04-1.10] and 1.03 [1.00-1.07]). Fasting
      plasma glucose was associated with unadjusted but not adjusted overall graft
      failure (1.09 [1.01-1.18] and 1.07 [0.98-1.17]). Neither 2hPG nor fasting plasma
      glucose was associated with death-censored graft loss (P=0.578 and P=0.896).
      Compared with recipients with normal glucose tolerance, recipients with
      posttransplantation diabetes mellitus showed a tendency toward increased overall
      multiadjusted graft failure (1.30 [0.98-1.73]). This was not observed in patients
      with impaired fasting glucose or impaired glucose tolerance. CONCLUSIONS: In this
      study, 2hPG was associated with overall graft failure but not death-censored
      graft failure. The link between 2hPG and graft failure may be explained by the
      association with mortality.

PMID- 22965265
TI  - Individual lifetime pollen and nectar foraging preferences in bumble bees.
AB  - Foraging specialization plays an important role in the ability of social insects
      to efficiently allocate labor. However, relatively little is known about the
      degree to which individual bumble bees specialize on collecting nectar or pollen,
      when such preferences manifest, and if individuals can alter their foraging
      preferences in response to changes in the colony workforce. Using Bombus
      impatiens, we monitored all foraging visits made by every bee in multiple
      colonies and showed that individual foragers exhibit consistent lifetime foraging
      preferences. Based upon the distribution of foraging preferences, we defined
      three forager types (pollen specialists, nectar specialists, and generalists). In
      unmanipulated colonies, 16-36 % of individuals specialized (>=90 % of visits) on
      nectar or pollen only. On its first day of foraging, an individual's foraging
      choices (nectar only, pollen only, or nectar and pollen) significantly predicted
      its lifetime foraging preferences. Foragers that only collected pollen on their
      first day of foraging made 1.61- to 1.67-fold more lifetime pollen foraging
      visits (as a proportion of total trips) than foragers that only collected nectar
      on their first foraging day. Foragers were significantly larger than bees that
      stayed only in the nest. We also determined the effect of removing pollen
      specialists at early (brood present) or later (brood absent) stages in colony
      life. These results suggest that generalists can alter their foraging preferences
      in response to the loss of a small subset of foragers. Thus, bumble bees exhibit
      individual lifetime foraging preferences that are established early in life, but
      generalists may be able to adapt to colony needs.

PMID- 22965266
TI  - Comparison of molecular subtyping with BluePrint, MammaPrint, and TargetPrint to
      local clinical subtyping in breast cancer patients.
AB  - PURPOSE: To compare breast cancer subtyping with the three centrally assessed
      microarray-based assays BluePrint, MammaPrint, and TargetPrint with locally
      assessed clinical subtyping using immunohistochemistry (IHC) and fluorescence in
      situ hybridization (FISH). METHODS: BluePrint, MammaPrint, and TargetPrint were
      all performed on fresh tumor samples. Microarray analysis was performed at
      Agendia Laboratories, blinded for clinical and pathological data. IHC/FISH
      assessments were performed according to local practice at each institution;
      estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
      factor receptor 2 (HER2) assessments were performed on 132 samples, and Ki-67 on
      79 samples. RESULTS: The concordance between BluePrint and IHC/FISH subtyping was
      94 % for the Luminal-type, 95 % for the HER2-type, and 94 % for the Basal-type
      subgroups. The concordance of BluePrint with subtyping using mRNA single gene
      readout (TargetPrint) was 96 % for the Luminal-type, 97 % for the HER2-type, and
      98 % for the Basal-type subgroups. The concordance for substratification into
      Luminal A and B using MammaPrint and Ki-67 was 68 %. The concordance between
      TargetPrint and IHC/FISH was 97 % for ER, 80 % for PR, and 95 % for HER2.
      CONCLUSIONS: The implementation of multigene assays such as TargetPrint,
      BluePrint, and MammaPrint may improve the clinical management of breast cancer
      patients. High discordance between Luminal A and B substratification based on
      MammaPrint versus locally assessed Ki-67 or grade indicates that chemotherapy
      decisions should not be based on the basis of Ki-67 readout or tumor grade alone.
      TargetPrint serves as a second opinion for those local pathology settings where
      high-quality standardization is harder to maintain.

PMID- 22965267
TI  - Splenic abscess after sleeve gastrectomy: a report of two cases.
AB  - OBJECTIVE: Partial demarcation and infarction of the upper pole of the spleen is
      not a rare occurrence after laparoscopic sleeve gastrectomy (LSG). However,
      development of an abscess in the absence of leakage is extremely rare. CASE
      REPORTS: We present herein two unusual case reports of splenic abscess in
      patients following LSG.

PMID- 22965268
TI  - Nestedness and successional trajectories of macroinvertebrate assemblages in man
      made wetlands.
AB  - Current successional models, primarily those based on floral succession, propose
      several distinct trajectories based on the integration of two key hypotheses from
      succession theory: convergence versus divergence in species composition among
      successional sites, and progression towards versus deviation from a desired
      reference state. We applied this framework to faunal succession, including
      differential colonization between active and passive dispersers, and the nested
      patterns generated as a consequence of this peculiarity. Nine man-made wetlands
      located in three different areas, from 0-3 years from wetland creation, were
      assessed. In addition, 91 wetlands distributed throughout the region were used as
      references for natural macroinvertebrate communities. We predicted the following:
      (1) highly nested structures in pioneering assemblages will decrease to lower mid
      term values due to a shift from active pioneering taxa to passive disperser ones;
      (2) passive idiosyncratic taxa will elicit divergent successional trajectories
      among areas; (3) the divergent trajectories will provoke lower local and higher
      regional diversity values in the mid-term assemblages than in pioneer
      assemblages. Our results were largely congruent with hypotheses (1) and (2),
      diverging from the anticipated patterns only in the case of the temporary
      wetlands area. However, overall diversity trends based on hypothesis (3) did not
      follow the expected pattern. The divergent successional trajectories did not
      compensate for regional biodiversity losses that occurred as a consequence of
      pioneering colonizer decline over time. Consequently, we suggest reconsidering
      wetland construction for mitigation purposes within mid-term time frames (<= 3
      years). Wetlands may not offset, within this temporal scenario, regional
      biodiversity loss because the ecosystem may not support idiosyncratic taxa from
      natural wetlands.

PMID- 22965269
TI  - Short-term general recidivism risk of juvenile sex offenders: validation of the
      Washington State Juvenile Court Prescreen Assessment.
AB  - It is important to examine whether general risk-assessment instruments developed
      for nonsex offenders can also be applied to sex offenders, because juvenile sex
      offenders are much more likely to reoffend with a nonsexual offense than a sexual
      offense. This study examined to what extent the Washington State Juvenile Court
      Prescreen Assessment (WSJCPA) can be used to assess the risk for general
      recidivism among different types of juvenile sex offenders. The predictive
      validity of the WSJCPA was examined separately for the following subgroups: boys
      convicted for a misdemeanor sexual offense against a peer (n = 381), boys
      convicted for a felony sexual offense against a peer (n = 282), boys convicted
      for a sexual offense against a younger child (n = 521), and girls convicted for a
      sexual offense (n = 71) and two comparison groups of male (n = 15,155) and female
      (n = 5,811) juvenile nonsex offenders. The area under the receiver operating
      characteristic curve scores for general recidivism ranged between .64 and .73.
      The WSJCPA proved to be at least equally predictive of general offending among
      juvenile sex and nonsex offenders groups. 

PMID- 22965264
TI  - Parasomnias: an updated review.
AB  - Parasomnias are abnormal behaviors emanating from or associated with sleep.
      Sleepwalking and related disorders result from an incomplete dissociation of
      wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke
      repeated cortical arousals, or promote sleep inertia lead to NREM parasomnias by
      impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a
      biomarker of arousal instability in NREM sleep, are noted in sleepwalking
      disorders. Sleep-related eating disorder (SRED) is characterized by a disruption
      of the nocturnal fast with episodes of feeding after an arousal from sleep. SRED
      is often associated with the use of sedative-hypnotic medications; in particular,
      the widely prescribed benzodiazepine receptor agonists. Recently, compelling
      evidence suggests that nocturnal eating may in some cases be a nonmotor
      manifestation of Restless Legs Syndrome (RLS). rapid eye movement (REM) Sleep
      Behavior Disorder (RBD) is characterized by a loss of REM paralysis leading to
      potentially injurious dream enactment. The loss of atonia in RBD often predates
      the development of Parkinson's disease and other disorders of synuclein
      pathology. Parasomnia behaviors are related to an activation (in NREM
      parasomnias) or a disinhibition (in RBD) of central pattern generators (CPGs).
      Initial management should focus on decreasing the potential for sleep-related
      injury followed by treating comorbid sleep disorders. Clonazepam and melatonin
      appear to be effective therapies in RBD, whereas paroxetine has been reported
      effective in some cases of sleep terrors. At this point, pharmacotherapy for
      other parasomnias is less certain, and further investigations are necessary.

PMID- 22965270
TI  - Youths' views on corruption control in China: politics and social censure.
AB  - It has been asserted that criminal law and common morality are not sufficient
      terms to describe specific behaviors as corruption because those in power have
      the capacity to include or exclude certain behavior as a category in the law.
      Thus, corruption should not be just treated as an objective behavioral category
      but as a form of social censure. This article reports on a quantitative and
      qualitative study that collected the views of Chinese youth on the control of
      corruption in China. It was found that they agreed with the moral-negative
      judgements behind the censure of corruption, and that bureaucratic forces can be
      mobilised to punish the corrupt and degrade their status. Mediation analysis
      discovered that political functions mediate the association between the moral
      negative nature and bureaucratic form of the censure of corruption and status
      degradation of the censured. 

PMID- 22965271
TI  - Reducing bacterial contamination inside fluid catch bag in 25-gauge vitrectomy by
      use of 0.25 % povidone-iodine ocular surface irrigation.
AB  - To examine the bacterial detection rate in infusion fluid collected inside the
      fluid catch bag during 25-gauge (25G) vitrectomy when the ocular surface was
      irrigated with infusion fluid or 0.25 % povidone-iodine. Two groups using
      different fluids for ocular surface irrigation during 25G vitrectomy were
      studied. Fifty-five consecutive eyes received ocular surface irrigation with
      infusion fluid (IF group) and 52 consecutive eyes with 0.25 % povidone-iodine (PI
      group). Samples of ocular surface fluid were collected at the beginning of
      surgery and samples of infusion fluid inside the fluid catch bag were collected
      at the end of surgery for bacteriological cultures. At the beginning of surgery,
      the bacterial detection rates in ocular surface fluid samples were 5.8 % (3 of 52
      eyes) in the IF group and 7.7 % (4 of 52 eyes) in the PI group, with no
      significant difference (P = 0.6955). At the end of surgery, the bacterial
      detection rates in infusion fluid collected inside the fluid catch bag were 23.1
      % (12 of 52 eyes) in the IF group and 3.8 % (2 of 52 eyes) in the PI group, with
      a significant difference (P = 0.0041). No endophthalmitis occurred in either
      group. These results demonstrate the risk of bacterial contamination when
      surgical instruments fall accidentally into the fluid catch bag during
      conventional 25G vitrectomy. Irrigating the ocular surface with 0.25 % povidone
      iodine instead of infusion fluid significantly reduces the bacterial
      contamination rate in the fluid catch bag.

PMID- 22965272
TI  - Intraocular graft unfolding techniques in descemet membrane endothelial
      keratoplasty.
AB  - OBJECTIVE: To define various Descemet graft unfolding techniques in Descemet
      membrane endothelial keratoplasty. METHODS: In a retrospective analysis, the
      surgical videos of 100 consecutive Descemet membrane endothelial keratoplasty
      cases with at least 6 months of follow-up were evaluated and categorized. The
      Descemet graft unfolding methods were categorized into 4 basic techniques and 3
      auxiliary techniques. RESULTS: All Descemet membrane endothelial keratoplasty
      surgical procedures could be completed using (a combination of) 4 Descemet graft
      unfolding techniques: (1) standardized no-touch graft unfolding using a double
      roll, (2) carpet unrolling while fixating 1 graft edge (Dirisamer technique), (3)
      small air bubble-assisted unrolling (Dapena maneuver), (4) the single sliding
      cannula maneuver. Additional maneuvers included turning over the graft when
      oriented upside down (flushing); manual graft centration with a cannula; and
      bubble bumping to unfold peripheral inward folds. In 73% of surgical procedures,
      technique 1 was used, while a combination of techniques was used in 44% and
      auxiliary techniques in 62%. None of the techniques showed a correlation with the
      best-corrected visual acuity, endothelial cell density, or postoperative
      complication rate (P > .10). CONCLUSIONS: Descemet membrane endothelial
      keratoplasty may be further facilitated by using controlled techniques for
      unfolding the Descemet graft inside the recipient anterior chamber, either as
      stand-alone techniques or used in various combinations.

PMID- 22965273
TI  - Serum, urine, and breath-related biomarkers in the diagnosis of obstructive sleep
      apnea in children:  is it for real?
AB  - PURPOSE OF REVIEW: The scarcity of pediatric sleep laboratories has thus far
      precluded timely diagnosis and treatment of pediatric obstructive sleep apnea
      (OSA), thereby increasing the risk for residual OSA-associated morbidities.
      Recent developments in transcriptomics, proteomics, and exhaled condensate
      biomarker discovery will be reviewed in the context of exploring the validity of
      such methods towards development of reliable and validated diagnostic approaches
      for pediatric OSA. RECENT FINDINGS: Gene expression arrays have revealed
      significant and reproducible changes in a restricted number of genes that should
      enable discriminatory ability in the recognition of OSA in children. Similarly, a
      number of urinary proteins have been identified that display outstanding receiver
      operator properties towards the diagnosis of pediatric OSA. The technological
      improvements in both exhaled breath online high-pressure fast chromatography and
      biosensor surfaces with affinity for volatile compounds should also permit
      noninvasive diagnosis of pediatric OSA when combined and integrated with
      computational methods. SUMMARY: It is likely that the modest efforts thus far
      realized in the context of biomarker discovery for the diagnosis and clinical
      monitoring of OSA in children will experience major acceleration in the upcoming
      years and lead to a completely novel paradigm in the screening and diagnosis of
      this disease.

PMID- 22965274
TI  - What physicians need to know about dreams and dreaming.
AB  - PURPOSE OF REVIEW: An overview of the current status of dream science is given,
      designed to provide a basic background of this field for the sleep-interested
      physician. RECENT FINDINGS: No cognitive state has been more extensively studied
      and is yet more misunderstood than dreaming. Much older work is methodologically
      limited by lack of definitions, small sample size, and constraints of theoretical
      perspective, with evidence equivocal as to whether any special relationship
      exists between rapid eye movement (REM) sleep and dreaming. As the relationship
      between dreams and REM sleep is so poorly defined, evidence-based studies of
      dreaming require a dream report. The different aspects of dreaming that can be
      studied include dream and nightmare recall frequency, dream content, dreaming
      effect on waking behaviors, dream/nightmare associated medications, and
      pathophysiology affecting dreaming. SUMMARY: Whether studied from behavioral,
      neuroanatomical, neurochemical, pathophysiological or electrophysiological
      perspectives, dreaming reveals itself to be a complex cognitive state affected by
      a wide variety of medical, psychological, sleep and social variables.

PMID- 22965275
TI  - The cystic fibrosis airway microbiome.
AB  - PURPOSE OF REVIEW: Culture and molecular approaches have established that lower
      airway infections are polymicrobial. We consider how this new perspective in
      cystic fibrosis (CF) may affect treatment choices. RECENT FINDINGS: Standard
      clinical microbiology of CF infection exacerbations often fails to provide
      indications of microbial causes that may drive the onset of exacerbation and the
      anticipated bacteriologic responses to the usual parenteral antibiotics
      prescribed as treatment. Antimicrobial responses by nonclassical members of the
      CF airway microbiome may explain why most patients clinically improve. These
      other organisms contribute to disease either directly as pathogens missed by
      conventional microbiology or through synergy with conventional pathogens. With
      these considerations, therapy may best be guided by directed antibiotic therapy
      to numerically significant isolates. An example is the Streptococcus milleri
      group, which we now believe to represent new pathogens that profile the
      exacerbations of infection in the CF lung and that necessitate specific
      antibiotic therapy to prevent loss of lung function and reduce frequency of
      exacerbations. SUMMARY: A comprehensive understanding of airway infections offers
      the potential for improved disease management in CF patients. Accurate
      quantitative microbiology will be a prerequisite for routine intervention based
      on the polymicrobial perspective of CF infection exacerbations.

PMID- 22965276
TI  - Effects of Aspergillus fumigatus colonization on lung function in cystic
      fibrosis.
AB  - PURPOSE OF REVIEW: Aspergillus fumigatus is frequently isolated from cystic
      fibrosis (CF) patients and is notorious for its role in the debilitating
      condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients
      suffer from perpetual microorganism-related lung disease, it is unclear whether
      A. fumigatus colonization has a role in causing accelerated lung function decline
      and whether intervention is necessary. RECENT FINDINGS: A. fumigatus morbidity
      appears to be related to cystic fibrosis transmembrane conductance regulator
      dependant function of the innate immune system. A. fumigatus-colonized patients
      have a lower lung capacity, more frequent hospitalizations and more prominent
      radiological abnormalities than noncolonized patients. Treatment with antifungal
      agents can be of value but has several drawbacks and a direct effect on lung
      function is yet to be shown. SUMMARY: A. fumigatus appears to have an important
      role in CF lung disease, not exclusive to the context of ABPA. However, a causal
      relationship still needs to be confirmed. Study observations and trends indicate
      a need to further elucidate the mechanisms of A. fumigatus interactions with the
      host innate immune system and its role in CF lung morbidity.

PMID- 22965277
TI  - Benchmarking to improve the quality of cystic fibrosis care.
AB  - PURPOSE OF REVIEW: Benchmarking involves the ascertainment of healthcare programs
      with most favorable outcomes as a means to identify and spread effective
      strategies for delivery of care. The recent interest in the development of
      patient registries for patients with cystic fibrosis (CF) has been fueled in part
      by an interest in using them to facilitate benchmarking. This review summarizes
      reports of how benchmarking has been operationalized in attempts to improve CF
      care. RECENT FINDINGS: Although certain goals of benchmarking can be accomplished
      with an exclusive focus on registry data analysis, benchmarking programs in
      Germany and the United States have supplemented these data analyses with
      exploratory interactions and discussions to better understand successful
      approaches to care and encourage their spread throughout the care network.
      SUMMARY: Benchmarking allows the discovery and facilitates the spread of
      effective approaches to care. It provides a pragmatic alternative to traditional
      research methods such as randomized controlled trials, providing insights into
      methods that optimize delivery of care and allowing judgments about the relative
      effectiveness of different therapeutic approaches.

PMID- 22965278
TI  - Functional characterization of the recombinant HIV-neutralizing monoclonal
      antibody 2F5 produced in maize seeds.
AB  - Monoclonal antibodies (mAbs) that neutralize human immunodeficiency virus (HIV)
      can be used as microbicides to help prevent the spread of HIV in human
      populations. As an industry standard, HIV-neutralizing mAbs are produced as
      recombinant proteins in mammalian cells, but the high manufacturing costs and
      limited capacity reduce the ability of target populations in developing countries
      to gain access to these potentially life-saving medicines. Plants offer a more
      cost-effective and deployable production platform because they can be grown
      inexpensively and on a large scale in the region where the products are required.
      Here we show that the maize-derived HIV-neutralizing mAb 2F5 is assembled
      correctly in planta and binds to its antigen with the same affinity as 2F5
      produced in mammalian cells. Although 2F5 has been produced at high levels in non
      plant platforms, the yield in maize seeds is lower than previously achieved with
      another HIV-neutralizing mAb, 2G12. This suggests that the intrinsic properties
      of the antibody (e.g. sensitivity to specific proteases) and the environment
      provided by the production host (e.g. the relative abundance of different
      proteases, potential transgene silencing) may combine to limit the accumulation
      of some antibodies on a case-by-case basis.

PMID- 22965279
TI  - Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by
      targeting the integrin receptor of tumor cells.
AB  - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      promising candidate for cancer therapeutics that exhibits the ability to
      preferentially induce apoptosis in malignant cells. RGD peptides bind to the
      integrins, alphanubeta3 and alphanubeta5, which are selectively expressed in
      tumor neovasculature and at the surface of certain tumor cells. To enhance the
      antitumor effect, an RGD-TRAIL protein, in which TRAIL was fused with the RGD
      motif-containing cell adhesive sequence, GRGDNP (gly-arg-gly-asp-asn-pro), was
      constructed and evaluated for bioactivity. The soluble TRAIL and RGD-TRAIL
      proteins were expressed in Escherichia coli BL21 (DE3) and purified using a non
      denaturing method. The antitumor effect of the purified RGD-TRAIL on cell
      proliferation was evaluated in vitro using MTT and wound healing assays and cell
      apoptosis was assessed by Hoechst 33342 staining and PARP expression analysis.
      The results revealed that RGD-TRAIL inhibited the proliferation of multiple tumor
      cell lines (A549, NCI-H1299 and HCC827). Western blot analysis demonstrated that
      the treatment of tumor cells with RGD-TRAIL activated the apoptotic pathway by
      the cleavage of PARP, in the same way as wild-type TRAIL (wtTRAIL). These results
      demonstrate that RGD-TRAIL possesses more potent antitumor effects than wtTRAIL
      and, therefore, merits further investigation in preclinical and clinical studies.

PMID- 22965280
TI  - Minimizing back exchange in the hydrogen exchange-mass spectrometry experiment.
AB  - The addition of mass spectrometry (MS) analysis to the hydrogen exchange (HX)
      proteolytic fragmentation experiment extends powerful HX methodology to the study
      of large biologically important proteins. A persistent problem is the degradation
      of HX information due to back exchange of deuterium label during the
      fragmentation-separation process needed to prepare samples for MS measurement.
      This paper reports a systematic analysis of the factors that influence back
      exchange (solution pH, ionic strength, desolvation temperature, LC column
      interaction, flow rates, system volume). The many peptides exhibit a range of
      back exchange due to intrinsic amino acid HX rate differences. Accordingly, large
      back exchange leads to large variability in D-recovery from one residue to
      another as well as one peptide to another that cannot be corrected for by
      reference to any single peptide-level measurement. The usual effort to limit back
      exchange by limiting LC time provides little gain. Shortening the LC elution
      gradient by 3-fold only reduced back exchange by ~2%, while sacrificing S/N and
      peptide count. An unexpected dependence of back exchange on ionic strength as
      well as pH suggests a strategy in which solution conditions are changed during
      sample preparation. Higher salt should be used in the first stage of sample
      preparation (proteolysis and trapping) and lower salt (<20 mM) and pH in the
      second stage before electrospray injection. Adjustment of these and other factors
      together with recent advances in peptide fragment detection yields hundreds of
      peptide fragments with D-label recovery of 90% +/- 5%.

PMID- 22965282
TI  - Needling the status quo.

PMID- 22965281
TI  - Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity
      and pharynx.
AB  - OBJECTIVES: Two million new users will abuse prescription narcotics this year,
      most commonly hydrocodone. The most commonly prescribed form is hydrocodone
      acetaminophen (HA). Many individuals crush the tablets and snort the product to
      take advantage of the rapid transmucosal delivery of narcotics. The resultant
      pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been
      described only in a few case studies. STUDY DESIGN: Retrospective chart review.
      METHODS: Two private and one academic otolaryngology practices in Kentucky
      searched their patient charts for patients with morbidity from intranasal abuse
      of hydrocodone acetaminophen tablets. We identified thirty-five patients who
      presented for treatment between 2004 and 2011. RESULTS: The majority of patients
      will initially deny the behavior, frequently delaying diagnosis. Physical exam
      findings of white powder covering an underlying nasal mucosal necrosis are
      characteristic of this condition during active INHAA. Follow up was limited as
      only 26% returned for follow-up care. Patients commonly presented with orofacial
      nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis
      or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients
      presented with septal perforations, and 26% with palatal perforations. Two cases
      of invasive fungal sinusitis were clearly documented, with one resulting in
      death. CONCLUSIONS: The vast majority of cases presented with characteristic
      physical findings that included acute necrosis of soft tissue, which can progress
      to destroy oronasal structures. In the absence of invasive fungal disease, the
      condition is self-limited after cessation of INHAA and performance of local nasal
      debridement and nasal hygiene.

PMID- 22965283
TI  - Facing stroke, message from Asia. Abstracts of the Asia Pacific Stroke Conference
      2012, the Annual Conference of the Asia Pacific Stroke Organization (APSO).
      Tokyo, Japan. September 10-12, 2012.

PMID- 22965284
TI  - Using HPV prevalence to predict cervical cancer incidence.
AB  - Knowledge of a country's cervical cancer (CC) burden is critical to informing
      decisions about resource allocation to combat the disease; however, many
      countries lack cancer registries to provide such data. We developed a prognostic
      model to estimate CC incidence rates in countries without cancer registries,
      leveraging information on human papilloma virus (HPV) prevalence, screening, and
      other country-level factors. We used multivariate linear regression models to
      identify predictors of CC incidence in 40 countries. We extracted age-specific
      HPV prevalence (10-year age groups) by country from a meta-analysis in women with
      normal cytology (N = 40) and matched to most recent CC incidence rates from
      Cancer Incidence in Five Continents when available (N = 36), or Globocan 2008 (N
      = 4). We evaluated country-level behavioral, economic, and public health
      indicators. CC incidence was significantly associated with age-specific HPV
      prevalence in women aged 35-64 (adjusted R-squared 0.41) ("base model"). Adding
      geographic region to the base model increased the adjusted R-squared to 0.77, but
      the further addition of screening was not statistically significant. Similarly,
      country-level macro-indicators did not improve predictive validity. Age-specific
      HPV prevalence at older ages was found to be a better predictor of CC incidence
      than prevalence in women under 35. However, HPV prevalence could not explain the
      entire CC burden as many factors modify women's risk of progression to cancer.
      Geographic region seemed to serve as a proxy for these country-level indicators.
      Our analysis supports the assertion that conducting a population-based HPV survey
      targeting women over age 35 can be valuable in approximating the CC risk in a
      given country.

PMID- 22965285
TI  - Total airway reconstruction.
AB  - We present a case of obstructive sleep apnea (OSA) that required multilevel
      surgical correction of the airway and literature review and discuss the role
      supraglottic laryngeal collapse can have in OSA. A 34-year-old man presented to a
      tertiary otolaryngology clinic for treatment of OSA. He previously had nasal and
      palate surgeries and a Repose tongue suspension. His residual apnea hypopnea
      index (AHI) was 67. He had a dysphonia associated with a true vocal cord
      paralysis following resection of a benign neck mass in childhood. He also
      complained of inspiratory stridor with exercise and intolerance to continuous
      positive airway pressure. Physical examination revealed craniofacial hypoplasia,
      full base of tongue, and residual nasal airway obstruction. On laryngoscopy, the
      paretic aryepiglottic fold arytenoid complex prolapsed into the laryngeal inlet
      with each breath. This was more pronounced with greater respiratory effort.
      Surgical correction required a series of operations including awake tracheostomy,
      supraglottoplasty, midline glossectomy, genial tubercle advancement,
      maxillomandibular advancement, and reconstructive rhinoplasty. His final AHI was
      1.9. Our patient's supraglottic laryngeal collapse constituted an area of
      obstruction not typically evaluated in OSA surgery. In conjunction with treating
      nasal, palatal, and hypopharyngeal subsites, our patient's supraglottoplasty
      represented a key component of his success. This case illustrates the need to
      evaluate the entire upper airway in a complicated case of OSA.

PMID- 22965286
TI  - Left ventricular noncompaction in patients with beta-thalassemia: uncovering a
      previously unrecognized abnormality.
AB  - Left ventricular noncompaction (LVNC) is a rare cardiomyopathy with potentially
      serious outcomes. It results in multiple and excessive trabeculations, deep
      intertrabecular recesses, and a thickened ventricular myocardium with two
      distinct layers, compacted and noncompacted. The condition is most commonly
      congenital; however, acquired forms have also been described. A recent report of
      LVNC detected in a beta-thalassemia twin suggested an association with cardiac
      siderosis. In a cross-sectional study of 135 transfusion-dependent patients with
      beta-thalassemia (130 major and 5 intermedia, mean age 29.6 +/- 7.7 years, 49.6%
      males) presenting for cardiac iron assessment by magnetic resonance imaging
      (MRI), we evaluated the prevalence and risk factors for LVNC. None of the
      patients had neuromuscular or congenital heart disease. Eighteen patients (13.3%;
      95% confidence interval [CI] = 8.6-20.1) fulfilled the preassigned strict
      criteria for LVNC on cardiac MRI. There were no statistically significant
      differences between patients with and without LVNC with respect to demographics;
      hemoglobin levels; splenectomy status; systemic, hepatic, and cardiac iron
      overload indices; hepatic disease and infection studies; or iron chelator type.
      Patients with LVNC were more likely to have heart failure (adjusted odds ratio =
      1.77; 95% CI = 0.29-10.89); although with high uncertainty. Patients with beta
      thalassemia have a higher prevalence of LVNC than normal individuals. As this
      finding could not be explained by conventional risk factors in this patient
      population, further investigation of the underlying mechanisms of LVNC is
      warranted. This remains crucial for an entity with adverse cardiac outcomes,
      especially in patients with beta-thalassemia where cardiac disease remains a
      primary cause of mortality.

PMID- 22965287
TI  - [Foreword].

PMID- 22965288
TI  - [Integration of integrative concepts -- a survey ].

PMID- 22965289
TI  - [What we do not take as (sufficiently) true].

PMID- 22965290
TI  - [Model projects in integrated oncology].

PMID- 22965291
TI  - [Looking to the future].

PMID- 22965292
TI  - Failure of pentagastrin-stimulated calcitonin testing in early manifestation of
      familial medullary thyroid cancer.
AB  - This case report describes three generations of a family with familial medullary
      thyroid cancer (RET gene mutation L790F). One of the three siblings-all of them
      carrier of the respective mutation-exhibited the absence of pathological basal
      and pentagastrin-stimulated calcitonin levels in spite of multifocal medullary
      thyroid microcancer. This case illustrates the challenge to consider the
      biological diversity of RET gene mutations in the clinical management of affected
      gene carriers.

PMID- 22965294
TI  - The use and efficacy of continuous glucose monitoring in type 1 diabetes treated
      with insulin pump therapy: a randomised controlled trial.
AB  - AIMS/HYPOTHESIS: The aim of this multicentre, randomised, controlled crossover
      study was to determine the efficacy of adding continuous glucose monitoring (CGM)
      to insulin pump therapy (CSII) in type 1 diabetes. METHODS: Children and adults
      (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to
      (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout,
      participants crossed over to the other arm for 6 months. Paediatric and adult
      participants were separately electronically randomised through the case report
      form according to a predefined randomisation sequence in eight secondary and
      tertiary centres. The primary outcome was the difference in HbA(1c) levels
      between arms after 6 months. RESULTS: Seventy-seven participants were randomised
      to the On/Off sequence and 76 to the Off/On sequence; all were included in the
      primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in
      favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol];
      95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of
      glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with
      sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm
      (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the
      Sensor On arm (6.8 +/- 2.5 vs 5.8 +/- 1.9, p < 0.0001), together with the
      frequency of use of the temporary basal rate (0.75 +/- 1.11 vs 0.26 +/- 0.47, p <
      0.0001) and manual insulin suspend (0.91 +/- 1.25 vs 0.70 +/- 0.75, p < 0.018)
      functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On
      and Sensor Off arm, respectively (p = 0.40). CONCLUSIONS/INTERPRETATION:
      Continuous glucose monitoring was associated with decreased HbA(1c) levels and
      time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More
      frequent self-adjustments of insulin therapy may have contributed to these
      effects.

PMID- 22965296
TI  - A photochemical mechanism for homochirogenesis. Part 2.
AB  - A theoretical investigation of the photochemistry of racemic compounds with
      circularly polarized light was undertaken. The exact solutions of the
      differential equations by numerical integration to the approximate solutions used
      in an earlier article were compared. The exact solutions showed that sequential
      reactions yield enhanced optical activities in the products. For irreversible
      reactions, all enantiomeric excesses are lost if the reactions are carried to
      completion, but appreciable resolution occurs in many cases for partial
      conversion. For reversible reactions, significant enantiomeric excesses are found
      at the photostationary state.

PMID- 22965295
TI  - A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets.
AB  - AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly
      produced by the intestinal L cells, with beneficial actions on pancreatic beta
      cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas
      in bioactive form, some observations indicate that GLP-1 may also be produced in
      the islets. We performed comprehensive morphological, functional and molecular
      studies to evaluate the presence and various features of a local GLP-1 system in
      human pancreatic islet cells, including those from type 2 diabetic patients.
      METHODS: The presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2
      was determined in human pancreas by immunohistochemistry with confocal
      microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors.
      GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser
      desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha
      and beta cell suspensions were obtained by enzymatic dissociation and FACS
      sorting. Glucagon and GLP-1 release were measured in response to nutrients.
      RESULTS: Confocal microscopy showed the presence of GLP-1-like and PC1/3
      immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in
      beta cells. The presence of GLP-1 in isolated islets was confirmed by
      immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not
      beta) cell fractions released GLP-1, which was regulated by glucose and arginine.
      PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1
      release was significantly higher from type 2 diabetic than from non-diabetic
      isolated islets. CONCLUSIONS/INTERPRETATION: We have shown the presence of a
      functionally competent GLP-1 system in human pancreatic islets, which resides in
      alpha cells and might be modulated by type 2 diabetes.

PMID- 22965297
TI  - Assessment of need of patients with schizophrenia: a study in Vellore, India.
AB  - BACKGROUND: and aims: There is a dearth of studies investigating the prevalence
      and factors associated with unmet needs in people with schizophrenia from low-
      and middle-income countries. We aimed to study prevalence and risk factors for
      unmet need. METHOD: A case-control study design was employed. One hundred and one
      (101) consecutive patients attending a psychiatric hospital were assessed using
      Camberwell Assessment of Need Short version (CANSAS) and Positive and Negative
      Syndrome Scale (PANSS). Multivariate analysis was employed to adjust for
      confounders. RESULTS: The majority of patients had many unmet needs. These unmet
      needs were significantly associated with lower education, poverty and persistent
      psychopathology on multivariate analysis. CONCLUSION: Unmet needs are associated
      with poverty, lower education and persistent psychopathology. There is a need to
      manage unmet needs, in addition to addressing psychopathology and poverty.

PMID- 22965298
TI  - Preschool based JASPER intervention in minimally verbal children with autism:
      pilot RCT.
AB  - In this pilot study, we tested the effects of a novel intervention (JASPER, Joint
      Attention Symbolic Play Engagement and Regulation) on 3 to 5 year old, minimally
      verbal children with autism who were attending a non-public preschool.
      Participants were randomized to a control group (treatment as usual, 30 h of ABA
      based therapy per week) or a treatment group (substitution of 30 min of JASPER
      treatment, twice weekly during their regular program). A baseline of 12 weeks in
      which no changes were noted in core deficits was followed by 12 weeks of
      intervention for children randomized to the JASPER treatment. Participants in the
      treatment group demonstrated greater play diversity on a standardized assessment.
      Effects also generalized to the classroom, where participants in the treatment
      group initiated more gestures and spent less time unengaged. These results
      provide further support that even brief, targeted interventions on joint
      attention and play can improve core deficits in minimally verbal children with
      ASD.

PMID- 22965299
TI  - Healthcare service use and costs for autism spectrum disorder: a comparison
      between medicaid and private insurance.
AB  - Healthcare costs and service use for autism spectrum disorder (ASD) were compared
      between Medicaid and private insurance, using 2003 insurance claims data in 24
      states. In terms of costs and service use per child with ASD, Medicaid had higher
      total healthcare costs ($22,653 vs. $5,254), higher ASD-specific costs ($7,438
      vs. $928), higher psychotropic medication costs($1,468 vs. $875), more speech
      therapy visits (13.0 vs. 3.6 visits), more occupational/physical therapy visits
      (6.4 vs. 0.9 visits), and more behavior modification/social skills visits (3.8
      vs. 1.1 visits) than private insurance (all p < 0.0001). In multivariate
      analysis, being enrolled in Medicaid had the largest effect on costs, after
      controlling for other variables. The findings emphasize the need for continued
      efforts to improve private insurance coverage of autism.

PMID- 22965300
TI  - Theory of mind, socio-emotional problem-solving, socio-emotional regulation in
      children with intellectual disability and in typically developing children.
AB  - This study has examined the link between social information processing (SIP) and
      socio-emotional regulation (SER) in 45 children with intellectual disability (ID)
      and 45 typically developing (TD) children, matched on their developmental age. A
      Coding Grid of SER, focusing on Emotional Expression, Social Behaviour and
      Behaviours towards Social Rules displayed by children in three dyadic contexts
      (neutral, competitive or cooperative) was applied. Correlational analyses
      highlighted specific "bi-directional" links between some abilities in SIP and in
      SER, presenting between-groups partial similarities and dissimilarities that
      allowed discussing the developmental delay versus difference hypotheses in ID
      children. Cluster cases analyses identified subgroups with variable patterns of
      links. In both groups, the SIP and some categories of SER varied depending on
      developmental age.

PMID- 22965301
TI  - t(11;14)(q23;q32) involving IGH and DDX6 in nodal marginal zone lymphoma.
AB  - Nodal marginal zone lymphoma (NMZL) is a primary nodal B-cell lymphoma that
      shares morphological and immunophenotypic characteristics with extranodal and
      splenic marginal zone lymphoma. Data on altered genes and signaling pathways are
      scarce in this rare tumor entity. To gain further insights into the genetic
      background of NMZL, seven cases were investigated by microarray analysis, G
      banding, and FISH. Chromosomal imbalances were observed in 3/7 cases (43%) with
      gains of chromosome arms 1q, 8q, and 12q being the most frequent findings.
      Furthermore, we identified a translocation t(11;14)(q23;q32) involving IGH and
      DDX6. Chromosomal walking, expression analysis, siRNA-mediated gene knockdown and
      a yeast two hybrid screen were performed for further characterization of the
      translocation in vitro. In siRNA experiments, DDX6 appeared not to be involved in
      NF-kappaB activation as frequently observed for genes promoting lymphomagenesis
      but was found to interfere with the expression of BCL6 and BCL2 in an NF-kappaB
      independent manner. In conclusion, we identified several unbalanced aberrations
      and a t(11;14) involving IGH and DDX6 providing evidence for a contribution of
      DDX6 to lymphomagenesis by deregulation of BCL6 in NMZL.

PMID- 22965302
TI  - Naringin inhibits chemokine production in an LPS-induced RAW 264.7 macrophage
      cell line.
AB  - Naringin has been reported to act as an effective anti-inflammatory compound. In
      a previous study, we demonstrated that the anti-inflammatory effect of naringin
      on lipopolysaccharide (LPS)-induced acute lung injury in mice correlated with the
      inhibition of the nuclear factor-kappaB (NF-kappaB) pathway. However, the effects
      and mechanism of action of naringin on LPS-induced chemokine expression are not
      yet fully understood. This study aimed to evaluate the effect of naringin on
      chemokine expression in LPS-induced RAW 264.7 macrophages and to provide insights
      into the possible underlying mechanisms. We found that the in vitro pre-treatment
      with naringin led to a significant attenuation in the LPS-induced secretion of
      interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and macrophage
      inflammatory protein-1alpha (MIP-1alpha). RT-qPCR demonstrated that naringin
      significantly reduced the LPS-induced upregulation of IL-8, MCP-1 and MIP-1alpha
      mRNA expression in a dose-dependent manner. Additionally, western blot analysis
      revealed that naringin effectively suppressed NF-kappaB activation by inhibiting
      the degradation of IkappaB-alpha and the translocation of p65. Naringin also
      attenuated MAPK activation by inhibiting the phosphorylation of ERK1/2, JNK and
      p38 MAPK. Taken together, these demonstrate that naringin reduces IL-8, MCP-1 and
      MIP-1alpha secretion and mRNA expression, possibly by blocking the activation of
      the NF-kappaB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages.

PMID- 22965303
TI  - Evidence at the point of practice change: lung cancer screening.

PMID- 22965304
TI  - The prevalence of visual impairment in older adults in mainland China: a
      systematic review and meta-analysis.
AB  - PURPOSE: This paper presents estimates of the prevalence of blindness and low
      vision among older adults over 50 years of age in mainland China. METHODS: All
      primary reports of population-based studies that reported the prevalence or
      incidence of visual impairment among older populations in mainland China were
      identified. Twenty-four population-based studies were included in this systematic
      review. Blindness is defined as visual acuity of less than 3/60, or a
      corresponding visual-field loss to less than 10 degrees in the better eye with
      the best possible correction; low vision is defined as visual acuity of less than
      6/18, but equal to or better than 3/60 in the better eye with the best possible
      correction. The pooled prevalence estimates of blindness and low vision were
      calculated assuming a random-effects model. Relative odds with 95% confidence
      intervals (95% CIs) were calculated, stratified by methodological and
      socioeconomic variables. RESULTS: The overall pooled prevalence of blindness was
      1.7% (95% CI 1.4-2.1). The results of the meta-regression showed the significance
      of a predictor variable: geographic region. The blindness rates per 100 older
      adults in various regions were 1.4 (0.9-2.0) in East China, and 1.4 (1.0-2.0) in
      Central China and 2.5 (1.9-3.2) in Western China. The overall pooled prevalence
      of low vision was 4.1% (3.4-5.1) and the independent pooled prevalence rates
      stratified by geographic region were 3.6% (2.6-5.1) in East China, 3.6% (2.4-5.2)
      in Central China and 5.2% (3.6-7.4) in Western China. CONCLUSIONS: Blindness or
      low vision affects approximately 5.8% Chinese adults older than 50 years. The
      prevalence of visual impairment, and especially blindness, vary greatly by the
      developmental status of geographic region.

PMID- 22965305
TI  - Use of transgenic oryzacystatin-I-expressing plants enhances recombinant protein
      production.
AB  - Plants are an effective and inexpensive host for the production of commercially
      interesting heterologous recombinant proteins. The Escherichia coli-derived
      glutathione reductase was transiently expressed as a recombinant model protein in
      the cytosol of tobacco plants using the technique of leaf agro-infiltration.
      Proteolytic cysteine protease activity progressively increased over time when
      glutathione reductase accumulated in leaves. Application of cysteine protease
      promoter-GUS fusions in transgenic tobacco identified a cysteine protease NtCP2
      expressed in mature leaves and being stress responsive to be expressed as a
      consequence of agro-infiltration. Transgenic tobacco plants constitutively
      expressing the rice cysteine protease inhibitor oryzacystatin-I had significantly
      lower cysteine protease activity when compared to non-transgenic tobacco plants.
      Lower cysteine protease activity in transgenic plants was directly related to
      higher glutathione reductase activity and also higher glutathione reductase
      amounts in transgenic plants. Overall, our work has demonstrated as a novel
      aspect that transgenic tobacco plants constitutively expressing an exogenous
      cysteine protease inhibitor have the potential for producing more recombinant
      protein which is very likely due to the reduced activity of endogenous cysteine
      protease.

PMID- 22965306
TI  - Graphene oxide as a matrix for the immobilization of glucose oxidase.
AB  - The adsorption of glucose oxidase (GOD) on graphene oxide (GO) nanoparticles
      without using any cross-linking reagents and/or additional surface modification
      was studied. Results of Fourier-transform infrared and ultraviolet-visible
      absorption spectroscopy confirmed that GOD was successfully immobilized on GO
      surface. The obtained immobilized GOD showed a wide range of pH stability and
      improved thermal and storage stability. In addition, GO exhibited good
      biocompatibility, which has potential advantages for biomedical and clinical
      diagnosis applications.

PMID- 22965308
TI  - Individual phenotypic variances in a family with Thiel-Behnke corneal dystrophy.
AB  - PURPOSE: To diagnose Thiel-Behnke dystrophy, an autosomal dominant disease of the
      anterior basement membrane/Bowman membrane complex and corneal stroma, currently
      relies primarily on the overall clinical presentation of patient complaints,
      inheritance pattern, and physical appearance of the corneal findings on slit-lamp
      examination. Key challenges to accurately identifying the disease are variable
      and often obscured morphology caused from secondary scarring, creating phenotypic
      deviation from the "classical" presentation, and mimicry of characteristics
      typical of other closely related dystrophies. In this report, we demonstrate the
      high degree of phenotypic variability that can be found in this disease. METHODS:
      A well-characterized family with an established diagnosis of Thiel-Behnke
      dystrophy mapped to chromosome 10 was evaluated along with the corresponding
      pedigree. Each individual was examined under slit lamp, and any apparent lesions
      were photographed. RESULTS: In total, 4 generations were represented with 20
      affected members accounted for, ranging from ages 11 to 86 years. We observed 4
      phenotypes in this family: (1) the majority displayed "honeycomb" reticular
      opacities consistent with Thiel-Behnke dystrophy, (2) several subjects showed
      more granular-like deposits in a geographic distribution, (3) younger subjects
      with possible early manifestations of the disease possessed small superficial
      vesicles, and (4) some eyes exhibited an intermediate form with 2 distinct
      disease presentations at different regions within the same cornea. Taken
      together, the pedigree demonstrated a wide continuous spectrum of phenotypes from
      a supposedly singular genetic disorder that may also vary based on the age of
      patient. CONCLUSIONS: These observations show that the clinical phenotypic
      appearance alone can result in a variety of different and conflicting diagnoses.
      With such potential for error, improvement in the diagnostic criteria is
      necessary.

PMID- 22965312
TI  - Role of miR-122 and lipid metabolism in HCV infection.
AB  - Hepatitis C virus (HCV) exhibits a narrow host range and a specific tissue
      tropism. Mice expressing major entry receptors for HCV permit viral entry, and
      therefore the species tropism of HCV infection is considered to be reliant on the
      expression of the entry receptors. However, HCV receptor candidates are expressed
      and replication of HCV-RNA can be detected in several nonhepatic cell lines,
      suggesting that nonhepatic cells are also susceptible to HCV infection. Recently
      it was shown that the exogenous expression of a liver-specific microRNA, miR-122,
      facilitated the efficient replication of HCV not only in hepatic cell lines,
      including Hep3B and HepG2 cells, but also in nonhepatic cell lines, including
      Hec1B and HEK-293T cells, suggesting that miR-122 is required for the efficient
      replication of HCV in cultured cells. However, no infectious particle was
      detected in the nonhepatic cell lines, in spite of the efficient replication of
      HCV-RNA. In the nonhepatic cells, only small numbers of lipid droplets and low
      levels of very-low-density lipoprotein-associated proteins were observed compared
      with findings in the hepatic cell lines, suggesting that functional lipid
      metabolism participates in the assembly of HCV. Taken together, these findings
      indicate that miR-122 and functional lipid metabolism are involved in the tissue
      tropism of HCV infection. In this review, we would like to focus on the role of
      miR-122 and lipid metabolism in the cell tropism of HCV.

PMID- 22965313
TI  - A proteomic approach to the analysis of the components of the phycobilisomes from
      two cyanobacteria with complementary chromatic adaptation: Fremyella diplosiphon
      UTEX B590 and Tolypothrix PCC 7601.
AB  - Tolypothrix PCC 7601 and Fremyella diplosiphon UTEX B590 can produce two
      alternative phycobilisome (PBS) rods. PE-PBSs with one phycocyanin (PC) disk and
      multiple phycoerythrin (PE) disks are found in cells grown under green light
      (GL). PC-PBSs with only PC disks are obtained from cells grown under red light
      (RL). In this manuscript, we show the localization of the linker proteins and
      ferredoxin-NADP(+) oxidoreductase (FNR) in the PC-PBS and of PE-PBS rods using
      visible spectroscopy and mass spectrometry. PE-PBSs with different [PE]/[PC]
      ratios and PC-PBSs with different [PC]/[AP] (AP, allophycocyanin) ratios were
      isolated. CpeC was the primary rod linker protein found in the PBSs with a
      [PE]/[PC] ratio of 1.1, which indicates that this is the rod linker at the
      interphase PC-PE. CpeC and CpeD were identified in the PBSs with a [PE]/[PC]
      ratio of 1.6, which indicates that CpcD is the linker between the first and the
      second PE hexamers. Finally, CpeC, CpeD, and CpeE were found in the PBSs with a
      [PE]/[PC] ratio of 2.9, indicating the position of CpeE between the second and
      third PE moieties. CpcI2 was identified in the two PC-PBSs obtained from cells
      grown under RL, which indicates that CpcI2 is the linker between the first and
      second PC hexamers. CpcH2 was identified only in the PC-PBSs from Tolypothrix
      with a high [PC]/[AP] ratio of 1.92, which indicates that CpcH2 is the linker
      between the second and third PC hexamers. The PC-PBSs contained the rod cap
      protein L(R)(10) (CpcD), but this protein was absent in the PE-PBSs. PE-PBSs
      (lacking L(R)(10)) incorporated exogenous rFNR in a stoichiometry of up to five
      FNRs per PBS. A maximum of two FNRs per PBS were found in PC-PBSs (with
      L(R)(10)). These observations support the hypothesis that FNR binds at the distal
      ends of the PBS rods in the vacant site of CpcD L(R)(10). Finally, the molecular
      mass of the core membrane linker (L(CM)) was determined to be 102 kDa from a mass
      spectrometry analysis.

PMID- 22965314
TI  - Spontaneous in vitro maturation of oocytes prior to ovarian tissue
      cryopreservation in natural cycles of oncologic patients.
AB  - PURPOSE: To evaluate the recovery rate and spontaneous in vitro maturation (IVM)
      of immature oocytes enclosed within or released from follicles during the
      processing of ovarian tissue prior to its cryopreservation. METHODS: Thirty-three
      oncologic patients who had not previously undergone chemo or radiotherapy
      underwent ovarian tissue cryopreservation (OTC) during natural menstrual cycles.
      Immature oocytes, enclosed within follicles or released during ovarian cortex
      processing, were collected and matured spontaneously in vitro for 48 h. Nuclear
      maturation was assessed every 24 h and the ability of the IVM oocytes to display
      a normal activation response following parthenogenetic activation was evaluated.
      The following outcome measures were also evaluated: disease, age, FSH, LH, E2, P4
      and AMH serum levels, menstrual cycle day, recovery and spontaneous IVM and
      parthenogenetic activation rates. RESULTS: Oocytes recovered per patient were 3.3
      +/- 0.7 (1.8-4.7 oocytes, 95CI), regardless of the menstrual phase. The mean
      number of IVM oocytes per patient was 1.3 +/- 0.2 oocytes (95CI: 0.8-1.8),
      regardless of menstrual phase (p = 0.86) and oocyte origin (p = 0.61). Forty-one
      percent of oocytes extruded the second polar body and formed one pronucleus after
      parthenogenetic activation. CONCLUSION: Twenty-one of the 33 women (63.6 %)
      requesting OTC produced at least one mature oocyte.

PMID- 22965315
TI  - Propofol increases u-opioid receptor expression in SH-SY5Y human neuroblastoma
      cells.
AB  - The aim of the present study was to explore the effect of propofol, a intravenous
      sedative-hypnotic agent used widely in inducing and maintaining anesthesia, on u
      opioid receptor (MOR) expression in a human neuronal cell line. SH-SY5Y human
      neuroblastoma cells were treated with various concentrations of propofol (1, 5,
      10 or 20 uM) for different lengths of time (6, 12 or 24 h). Real-time
      quantitative RT-PCR showed that at a concentration range of 1-10 uM, propofol
      increased MOR mRNA levels in a statistically significant dose- and time-dependent
      manner within 12 h of treatment. Western blot analyses demonstrated that propofol
      treatment for 12 h dose-dependently increased the MOR protein levels. In the 12-h
      SH-SY5Y-treated cells, propofol dose-dependently increased MOR density (Bmax) in
      the cell membranes. In addition, in the presence of the transcription inhibitor
      actinomycin D (1 mg/ml), propofol (10 uM) had no significant effect on the MOR
      mRNA levels over time. The results suggested that propofol dose- and time
      dependently enhances MOR expression in SH-SY5Y human neuroblastoma cells at the
      transcriptional level, leading to an increased density of ligand-binding MORs in
      the cell membranes. This study demonstrated for the first time a link between
      propofol and the opioid system, thereby providing new insights into propofol
      mechanism of action and potential for abuse.

PMID- 22965316
TI  - The other side of quality improvement in diabetes for seniors: a proposal for an
      overtreatment glycemic measure.

PMID- 22965317
TI  - Urethral reconstruction in lichen sclerosus.
AB  - PURPOSE OF REVIEW: Lichen sclerosus is a chronic skin disease that shows a
      predilection for the anogenital area and may involve anterior urethra causing
      stenosis. Surgical options in the management of urethral strictures caused by
      lichen sclerosus still represent a challenging issue. RECENT FINDINGS: Depending
      on the length and severity of urethral involvement, surgical management of lichen
      sclerosus urethral strictures can range from a simple meatotomy to a single or
      complex staged long repair using oral mucosa. Skin grafts or flaps are not
      recommended because skin could be involved by the disease. Perineal urethrostomy
      may represent the salvage solution in severe panurethral strictures. SUMMARY: One
      stage or staged repairs using oral mucosa grafts are the most recommended
      procedures for the treatment of lichen sclerosus urethral strictures, but
      derivative perineal urethrostomy may play an important role in severe situations.
      Patients require long-term follow-up and extensive counseling that enables them
      to fully grasp the chronic and progressive nature of the disease and to deal with
      it.

PMID- 22965318
TI  - Varicocelectomy in the treatment of testicular pain:  a review.
AB  - PURPOSE OF REVIEW: Varicoceles are a common finding in adolescent boys and men.
      Most are asymptomatic, although up to 10% may cause testicular pain. This study
      will review the use of varicocelectomy in the treatment of testicular pain in men
      with clinical varicoceles, as well as provide prognostic indicators for
      successful outcome. RECENT FINDINGS: Recent studies that examined the impact of
      varix ligation on preoperative testicular pain were reviewed. Most studies are
      retrospective and uncontrolled; although objective outcome measures were used in
      the majority. Varicocele grade, duration of discomfort, and the quality of pain
      tended to predict outcome but have not been universally supported. SUMMARY: On
      the basis of the majority of the recently published studies, varicocelectomy, in
      the properly chosen patients, results in significant improvement or resolution of
      testicular pain.

PMID- 22965319
TI  - Editorial comment on urethral reconstruction.

PMID- 22965320
TI  - Contemporary issues in varicocele management.

PMID- 22965321
TI  - Visible light photocatalysis of [2+2] styrene cycloadditions by energy transfer.

PMID- 22965322
TI  - Emergency neurological life support: intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a subset of stroke resulting from bleeding
      within the brain parenchyma of the brain. It is potentially lethal, and survival
      depends on ensuring an adequate airway, reversal of coagulopathy, and proper
      diagnosis. ICH was chosen as an emergency neurological life support (ENLS)
      protocol because intervention within the first critical hour may improve outcome,
      and it is helpful to have a protocol to drive care quickly and efficiently.

PMID- 22965323
TI  - Emergency neurological life support: traumatic spine injury.
AB  - Traumatic spine injuries (TSIs) carry significantly high risks of morbidity,
      mortality, and exorbitant health care costs from associated medical needs
      following injury. For these reasons, TSI was chosen as an ENLS protocol. This
      article offers a comprehensive review on the management of spinal column injuries
      using the best available evidence. Though the review focuses primarily on
      cervical spinal column injuries, thoracolumbar injuries are briefly discussed as
      well. The initial emergency department clinical evaluation of possible spinal
      fractures and cord injuries, along with the definitive early management of
      confirmed injuries, are also covered.

PMID- 22965324
TI  - Confounding by indication in retrospective studies of intracerebral hemorrhage:
      antiepileptic treatment and mortality.
AB  - INTRODUCTION: Intracerebral hemorrhage (ICH) is a highly fatal disease with few
      proven treatments. Data to guide clinician decisions for therapies, including
      antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH
      have provided conflicting results. We investigated the effect of AED treatment on
      90-day mortality after ICH in a large prospectively ascertained cohort. METHODS:
      We conducted a retrospective analysis of a prospectively assembled cohort of
      patients with ICH in the supratentorial regions, comparing 90-day mortality and
      modified Rankin Score among 543 patients treated with AED during hospitalization
      and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or
      deep hemispheric. RESULTS: Multivariate analysis demonstrated an association
      between AED treatment and reduced 90-day mortality in supratentorial ICH (OR =
      0.62, 95 % CI 0.42-0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 %
      CI 0.25-0.96, p = 0.04). When analyses were restricted to subjects surviving
      longer than 5 days from ICH, however, no association between AED treatment and a
      90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected,
      despite more than adequate power to detect the originally observed association.
      CONCLUSION: These results suggest that AED treatment in acute ICH is not
      associated with 90-day mortality or outcome and that any detected association
      could arise by confounding by indication, in which the most severely affected
      patients are those in whom AEDs are prescribed. They provide a cautionary example
      of the limitations of drawing conclusions about treatment effects from
      observational data.

PMID- 22965325
TI  - Blood transfusion is an important predictor of hospital mortality among patients
      with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Red blood cell (RBC) transfusion after aneurysmal subarachnoid
      hemorrhage (aSAH) has been associated with increased mortality but prior studies
      have not adequately adjusted for transfusion-indication bias. METHODS: This is a
      retrospective study of consecutive aSAH patients admitted to the intensive care
      units of two academic medical centers over a 7-year period. Data collection
      included demographics, World Federation of Neurosurgical Surgeons score (WFNS),
      modified Fisher score (mFisher), admission and nadir hemoglobin (Hb) level,
      vasospasm, cerebral infarction, acute lung injury, and hospital mortality. The
      association between RBC transfusion and mortality was evaluated using a
      multivariate logistic regression analysis using the propensity for RBC
      transfusion as a covariate. RESULTS: We identified 318 patients. The median age
      was 54 years (46, 65), and 204 (64 %) were females. Hospital mortality was 13 %
      (42/318). Seventy-two (23 %) patients were transfused. Predictors of transfusion
      were admit and nadir Hb levels (p < 0.001), age (p = 0.02), gender (0.008), WFNS
      score (p < 0.001), mFisher score (p = 0.009), surgical versus endovascular
      treatment (p < 0.001) and moderate to severe vasospasm (p = 0.025) were
      predictors of transfusion. After adjustment for probability of receiving RBC
      transfusion, APACHE IV and nadir Hb, transfusion remained independently
      associated with hospital mortality (OR 3.16, 95 % CI = 1.02-9.69, p = 0.047).
      CONCLUSIONS: Among patients with aSAH, RBC transfusion was independently
      associated with an increased mortality after adjustment for the most common
      clinical indications for transfusion.

PMID- 22965326
TI  - Where should critically ill neurologic brain hemorrhage patients go and can
      transfer harm them?

PMID- 22965328
TI  - Procedural learning of unstructured categories.
AB  - Unstructured categories are those in which the stimuli are assigned to each
      contrasting category randomly, and thus there is no rule- or similarity-based
      strategy for determining category membership. Intuition suggests that
      unstructured categories are likely to be learned via explicit memorization that
      is under the control of declarative memory. In contrast to this prediction,
      neuroimaging studies of unstructured-category learning have reported task-related
      activation in the striatum, but typically not in the hippocampus--results that
      seem more consistent with procedural learning than with a declarative-memory
      strategy. This article reports the first known behavioral test of whether
      unstructured-category learning is mediated by explicit strategies or by
      procedural learning. Our results suggest that the feedback-based learning of
      unstructured categories is mediated by procedural memory.

PMID- 22965329
TI  - Effects of ramosetron and dexamethasone on postoperative nausea, vomiting, pain,
      and shivering in female patients undergoing thyroid surgery.
AB  - PURPOSE: Some antiemetics are effective in the treatment of postoperative pain
      and shivering, as well as for postoperative nausea and vomiting (PONV). The aim
      of this study was to investigate the effects of ramosetron and dexamethasone on
      PONV, pain, and shivering and to determine the correlations between nausea, pain,
      and shivering. METHODS: For this study, 123 patients scheduled for thyroid
      surgery were randomly allocated to one of three groups: the control group (group
      C, n = 41), dexamethasone group (group D, n = 41), or the ramosetron group (group
      R, n = 41). The patients were treated intravenously with 2 mL of 0.9 % NaCl, 2 mL
      of 5 mg/mL dexamethasone, or 2 mL of 0.15 mg/mL ramosetron immediately after
      anesthesia. RESULTS: The overall incidence and severity of postoperative nausea
      and the level of antiemetic consumption were significantly lower in group R
      compared with group D, and these parameters were significantly lower in groups R
      and D than in group C. There were significant differences in the incidence and
      severity of shivering, severity of pain, and analgesic consumption between group
      C and group R or D, but the incidence of shivering, pain severity, and analgesic
      consumption did not differ between groups R and D. The severity of shivering was
      significantly lower in group R than in group D. The correlation coefficients for
      shivering and pain, shivering and nausea, and pain and nausea were 0.210 (P =
      0.010), 0.106 (P = 0.198), and 0.190 (P = 0.035), respectively, in group C.
      CONCLUSIONS: Two antiemetic drugs, ramosetron and dexamethasone, significantly
      reduced the incidence and severity of postoperative nausea and the need for
      administration of rescue antiemetic drugs. Furthermore, both drugs effectively
      decreased the severity of pain and shivering. Ramosetron was superior to
      dexamethasone for reducing nausea, antiemetic consumption, and the severity of
      nausea, but not for reducing the incidence of shivering. Further studies are
      required to elucidate the correlations between postoperative nausea, pain, and
      shivering, as a statistically significant but weak correlation was shown in the
      present study.

PMID- 22965330
TI  - A randomized comparison of the i-gel and the ProSeal laryngeal mask airway in
      pediatric patients: performance and fiberoptic findings.
AB  - PURPOSE: We compared the insertion performance of the pediatric size 1.5-3 i-gel
      airway device with that of the ProSeal laryngeal mask airway (PLMA) in
      anesthetized children in a prospective, randomized, controlled manner. METHODS:
      We included 134 children, aged 3 months to 15 years, scheduled for elective
      surgery under general anesthesia. They were randomly divided into the i-gel and
      the PLMA groups according to the airway device used. The primary outcome variable
      was oropharyngeal leak pressure. Other outcome variables were ease of insertion,
      required time for insertion, fiberoptic view, and first-attempt and overall
      success rates. RESULTS: There were no differences in the ease of insertion,
      insertion time, or leak pressure between the devices. Fiberoptic view was
      significantly better with the i-gel than with the PLMA (P = 0.002). The view was
      significantly better with the sizes 2, 2.5, and 3 i-gel than with the size 1.5 i
      gel (P = 0.02, 0.004 and 0.002, respectively), and the view was significantly
      better with the sizes 2.5 and 3 PLMA than with the size 1.5 PLMA (P = 0.02 and
      0.005, respectively). The first-attempt success rates were 94 and 97 % in the i
      gel and the PLMA groups, respectively; the success rates including the second
      attempt were 100 % in both groups. No children developed side effects requiring
      treatment with either device. CONCLUSION: Both the pediatric i-gel and the PLMA
      were successfully inserted in children. The fiberoptic view was better with the i
      gel than with the PLMA.

PMID- 22965331
TI  - Effects of epidural analgesia on labor length, instrumental delivery, and
      neonatal short-term outcome.
AB  - PURPOSE: We aimed to clarify whether the short-term adverse neonatal outcomes
      associated with epidural analgesia are due to the epidural analgesia itself or to
      the instrumental delivery. METHODS: A retrospective case-control study was
      conducted to evaluate the relationship between epidural analgesia, labor length,
      and perinatal outcomes. A total of 350 pregnant women at term who delivered under
      epidural analgesia (cases) were compared with 1400 patients without epidural
      analgesia (controls). RESULTS: Vacuum extraction (6.5 vs. 2.9 %) and cesarean
      section (19.9 vs. 11.1 %) were more frequently performed in the cases than
      controls (p < 0.001). Using a Kaplan-Meier algorithm, it was determined that the
      mean lengths of the 1st and 2nd stages of labor and the overall durations of
      labor and delivery were significantly longer in cases compared with controls. A
      Cox regression analysis showed that the longer labor remained even after
      adjustment for parity. The neonatal variables stratified by mode of delivery were
      not different in cases and controls, except for a slightly lower umbilical
      arterial pH in spontaneous delivery for the cases group. However, the Apgar
      scores and umbilical arterial pH were significantly lower in the neonates
      delivered by vacuum extraction compared with those in the neonates delivered by
      spontaneous delivery or cesarean section, regardless of whether epidural
      analgesia was performed. A multivariable analysis showed that vacuum extraction
      much more consistently affected the arterial pH than the analgesia itself (the
      beta coefficients were -0.036 for epidural analgesia vs. -0.050 for vacuum
      extraction). CONCLUSION: Epidural analgesia was associated with slowly
      progressing labor, thus resulting in an increased rate of instrumental delivery.
      This instrumental delivery appears to adversely affect the neonatal outcomes more
      strongly than the analgesia itself.

PMID- 22965332
TI  - Mechanism of falcipain-2 inhibition by alpha,beta-unsaturated benzo[1,4]diazepin
      2-one methyl ester.
AB  - Falcipain-2 (FP-2) is a papain-family cysteine protease of Plasmodium falciparum
      whose primary function is to degrade the host red cell hemoglobin, within the
      food vacuole, in order to provide free amino acids for parasite protein
      synthesis. Additionally it promotes host cell rupture by cleaving the skeletal
      proteins of the erythrocyte membrane. Therefore, the inhibition of FP-2
      represents a promising target in the search of novel anti-malarial drugs. A
      potent FP-2 inhibitor, characterized by the presence in its structure of the 1,4
      benzodiazepine scaffold and an alpha,beta-unsaturated methyl ester moiety capable
      to react with the Cys42 thiol group located in the active site of FP-2, has been
      recently reported in literature. In order to study in depth the inhibition
      mechanism triggered by this interesting compound, we carried out, through ONIOM
      hybrid calculations, a computational investigation of the processes occurring
      when the inhibitor targets the enzyme and eventually leads to an irreversible
      covalent Michael adduct. Each step of the reaction mechanism has been accurately
      characterized and a detailed description of each possible intermediate and
      transition state along the pathway has been reported.

PMID- 22965333
TI  - Levels of organochlorine pesticides residues in human adipose tissue, data from
      Tabasco, Mexico.
AB  - The objective of this study was to determine the levels of organochlorine
      pesticides HCB, alpha-beta-gamma-HCH, p,p'-DDE, o,p'-DDT and p,p'-DDT in 150
      adipose tissue of inhabitants of Tabasco, Mexico. The following pesticides were
      detected: p,p'-DDE in 100% of samples at mean 1.034 mg/kg; p,p'-DDT in 96.7% at
      mean 0.116 mg/kg; o,p'-DDT in 78.7% at mean 0.022 mg/kg and beta-HCH in 58.0% at
      mean 0.049 mg/kg. The pooled sample was divided according to sex of donors (75
      female and 75 male). Significantly higher levels of all organochlorine pesticides
      in females were found. The sample was divided into three age's ranges (15-28, 29
      45 and 46-84 years). The mean and median levels of beta-HCH, p,p'-DDE and Sigma
      DDT increase significantly (p < 0.05) from the first to the second and third
      group. The presence of organochlorine pesticide residues in Tabasco inhabitants
      is still observed, indicating sources of exposure to the pesticides.

PMID- 22965334
TI  - Assessment of natural radioactivity in phosphate ore, phosphogypsum and soil
      samples around a phosphate fertilizer plant in Nigeria.
AB  - The radionuclides present in phosphate ore, phosphogypsum and soil samples in the
      vicinity of a phosphate fertilizer plants in Nigeria were identified and their
      activity concentration determined to assess the potential radiation impact on the
      environment due to fertilizer production. The mean activity concentration of
      (238)U, (232)Th, and (40)K radionuclides in phosphate ore samples were 616 +/-
      38.6, BDL (Below Detection Level) and 323.7 +/- 57.5 Bq kg(-1) respectively. For
      the phosphogypsum, 334.8 +/- 8.8, 4.0 +/- 1.4, and 199.9 +/- 9.3 Bq kg(-1)
      respectively and for soil samples range from 20.5 +/- 7.3 to 175.7 +/- 10.5 Bq
      kg(-1) for (226)Ra, 15.5 +/- 1.5 to 50.4 +/- 0.6 Bq kg(-1) for (232)Th and 89.5
      +/- 8.1 to 316.1 +/- 41.3 Bq kg(-1) for (40)K respectively. The mean absorbed
      dose rate was 71.4 nGy h(-1). The mean annual effective dose was 86 MUSv.

PMID- 22965335
TI  - Residue and dissipation dynamics of lufenuron in tomato fruit using QuEChERS
      methodology.
AB  - One field experiment was conducted with lufenuron (Match((r)) 5% EC) on tomato
      crop during August 2011. The main objective was to understand the residue and
      dissipation behavior of insecticide lufenuron in tomato fruit samples. The
      dissipation behavior of lufenuron insecticide followed first-order rate kinetics
      at standard recommended dose application. The average initial deposit of
      lufenuron in tomato was observed to be 1.299 mg kg(-1)at single application rate.
      This lufenuron residue dissipated to bellow LOQ of 0.03 mg kg(-1) 21 days after
      the treatment. Lufenuron residues were lost with pre-harvest intervals of 7 days,
      following application at the recommended dose by manufacture.

PMID- 22965336
TI  - 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy
      of cardiac rhythm abnormalities: a report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Practice Guidelines and the
      Heart Rhythm Society. [corrected].

PMID- 22965337
TI  - Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use
      according to time passed after first-time myocardial infarction: a nationwide
      cohort study.
AB  - BACKGROUND: The cardiovascular risk after the first myocardial infarction (MI)
      declines rapidly during the first year. We analyzed whether the cardiovascular
      risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was
      associated with the time elapsed following first-time MI. METHODS AND RESULTS: We
      identified patients aged 30 years or older admitted with first-time MI in 1997 to
      2009 and subsequent NSAID use by individual-level linkage of nationwide
      registries of hospitalization and drug dispensing from pharmacies in Denmark. We
      calculated the incidence rates of death and a composite end point of coronary
      death or nonfatal recurrent MIs associated with NSAID use in 1-year time
      intervals up to 5 years after inclusion and analyzed risk by using multivariable
      adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients
      included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36
      747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5
      years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any
      NSAID in the years following MI was persistently associated with an increased
      risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1
      year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years)
      and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence
      interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28
      1.55]). CONCLUSIONS: The use of NSAIDs is associated with persistently increased
      coronary risk regardless of time elapsed after first-time MI. We advise long-term
      caution in the use of NSAIDs for patients after MI.

PMID- 22965338
TI  - Suramin inhibits the growth of nasopharyngeal carcinoma cells via the
      downregulation of osteopontin.
AB  - Radiotherapy is the principal therapy for nasopharyngeal carcinoma (NPC) at early
      stages. A number of chemotherapeutic methods have been used to inhibit the
      progression of NPC at elevated stages. Suramin has been reported to inhibit the
      growth of certain tumor cells via various pathways. In the present study, we
      aimed to analyze the effects of suramin on the proliferation of NPC cells (CNE
      2). Suramin was proved to demonstrate NPC cell growth-inhibiting effects both in
      a dose- and time-dependent manner. To determine the potential mechanisms of these
      effects, western blotting and flow cytometric analysis were performed. Suramin
      was found to have the potential to induce cell cycle arrest in S-phase CNE-2
      cells. Additionally, we found that the OPN level may decrease in suramin-treated
      CNE-2 cells. The changes of certain apoptosis- and p-AKT-associated proteins
      possibly regulating the OPN expression were measured by western blotting. In
      conclusion, suramin may function as a potential agent for the adjunctive therapy
      of NPC.

PMID- 22965339
TI  - The flip side of performance measures: limiting overtreatment.

PMID- 22965341
TI  - Research news impacting sports medicine:  food for thought or fun to learn.

PMID- 22965343
TI  - The traveling athlete:  from jet leg to jet lag.

PMID- 22965344
TI  - Update on the management of patellar instability.
AB  - Patellar instability is a complex topic that must be treated at the individual
      level. The majority of first-time patellar dislocations occur in sport, and there
      is a high rate of recurrence and ongoing symptoms. Physical examination and
      imaging studies can aid in treatment decisions. Patient symptoms, degree of
      trauma, compliance with therapy, anatomical factors, and desired activity levels
      influence management strategies (both operative and nonoperative). There is
      recent emphasis on the medial patellofemoral ligament and its involvement in
      patellar stability, and various surgical techniques have been studied; however
      there is no clear consensus.

PMID- 22965345
TI  - Greater trochanteric pain syndrome:  more than bursitis and iliotibial tract
      friction.
AB  - Disorders causing lateral hip pain are encountered frequently by physicians.
      Evaluating these problems can be challenging because of the myriad of potential
      causes, the complex anatomy of the peritrochanteric structures, and the
      inconsistently described etiologic factors. Misconceptions about the causes of
      lateral hip pain and tenderness are common, frequently leading to approaches that
      only provide temporary solutions rather than address the underlying pathology.
      Trochanteric bursitis is implicated frequently but is seldom the primary cause of
      pain in chronic cases. It is important to address hip rotator cuff tendinopathy
      and pelvic core instability. Treatment options include therapeutic exercise,
      physical modalities, corticosteroid injections, extracorporeal shock wave
      therapy, and regenerative injection therapies. For recalcitrant cases, surgery
      may be appropriate. By understanding the anatomy of the peritrochanteric
      structures, and the pathologic processes most likely responsible for
      symptomatology and dysfunction, the physician will be prepared to provide
      effective long-term solutions for this common problem.

PMID- 22965346
TI  - Imaging of the shoulder:  a comparison of MRI and ultrasound.
AB  - Magnetic resonance imaging (MRI) is well established as a powerful imaging
      modality for the shoulder. In the last decade, ultrasound has emerged as an
      effective imaging option, alongside MRI, for evaluation of the shoulder. With MRI
      and ultrasound, clinicians now have two viable advanced imaging options for the
      diagnostic evaluation of shoulder pain. This article discusses the advantages and
      disadvantages of ultrasound and MRI for the shoulder. Applications where
      ultrasound is considered the imaging test of choice, those where MRI is more
      advantageous, and those where both ultrasound and MRI are viable alternatives for
      shoulder imaging are discussed.

PMID- 22965347
TI  - Barefoot running:  biomechanics and implications for running injuries.
AB  - Despite the technological developments in modern running footwear, up to 79% of
      runners today get injured in a given year. As we evolved barefoot, examining this
      mode of running is insightful. Barefoot running encourages a forefoot strike
      pattern that is associated with a reduction in impact loading and stride length.
      Studies have shown a reduction in injuries to shod forefoot strikers as compared
      with rearfoot strikers. In addition to a forefoot strike pattern, barefoot
      running also affords the runner increased sensory feedback from the foot-ground
      contact, as well as increased energy storage in the arch. Minimal footwear is
      being used to mimic barefoot running, but it is not clear whether it truly does.
      The purpose of this article is to review current and past research on shod and
      barefoot/minimal footwear running and their implications for running injuries.
      Clearly more research is needed, and areas for future study are suggested.

PMID- 22965348
TI  - Volleyball injuries.
AB  - There has been a significant increase in the numbers of people playing indoor and
      beach volleyball since the early 1980s and, consequently, an increase in
      injuries. Most injuries are related to repetitive jumping and hitting the ball
      overhead. The ankle is the most commonly injured joint, but the knee, shoulder,
      low back, and fingers also are vulnerable. The shoulder in particular is subject
      to extreme torque when hitting and jump serving the ball. Some injuries have a
      predilection for those playing on sand versus those playing in an indoor court.
      The clinician caring for volleyball players should be aware of the types of
      injuries these players sustain and how to help them return to play promptly and
      appropriately. This article reviews the specific injuries that are most common as
      a result of participating in the sport of volleyball.

PMID- 22965349
TI  - Rowing:  sport-specific concerns for the team physician.
AB  - Rowing injuries occur mostly from overuse and are seen primarily in the back,
      rib, knee, and forearm. Many of these have a specific cause owing to the
      mechanics of the rowing stroke, which are discussed, as are sport-specific
      treatment strategies. Also discussed are specific injuries sustained on the
      rowing machine, emergency issues, and special population concerns.

PMID- 22965350
TI  - Caring for umpires, officials, and referees.
AB  - Umpires, referees, and sports officials have not been accorded the same attention
      as athletes by the sports medicine community. The physical and psychological
      demands of their jobs expose them to a unique constellation of medical,
      psychological, and orthopedic problems. Likewise their age, fitness level, and
      disease risk factors may warrant closer scrutiny for them and greater need for
      participation evaluation than the athletes with whom they share the field.
      Limited medical literature is published regarding the care of sports officials,
      even though they have a higher incidence of medical problems, cardiovascular
      risk, and orthopedic injuries than sports participants.

PMID- 22965351
TI  - Injuries and medical issues in softball.
AB  - Softball is enjoyed by millions of female and male athletes of all ages and
      competitive levels. Windmill pitchers are at risk for developing overuse injuries
      in the throwing arm. Improper mechanics and lack of pitch counts may increase the
      risk for developing a pitching-related injury. Softball-related overuse injuries
      include proximal biceps tendinitis, upper extremity stress fractures, and ulnar
      neuritis. Acute injuries commonly occur in the lower extremity and include both
      fractures and ligamentous injuries. Sliding injuries account for a significant
      number of these lower extremity injuries. The addition of breakaway bases and
      mandatory use of protective headgear by defensive players may decrease acute
      injuries commonly seen in softball. Off-season programs should stress proper
      throwing and sliding mechanics, core conditioning, and a lower extremity
      neuromuscular education program.

PMID- 22965352
TI  - Case report: Colonic MALT lymphoma.

PMID- 22965353
TI  - Primary malignant fibrous histiocytoma of Vater's Papilla: first reported case.

PMID- 22965354
TI  - Revising the human mutation rate: implications for understanding human evolution.
AB  - It is now possible to make direct measurements of the mutation rate in modern
      humans using next-generation sequencing. These measurements reveal a value that
      is approximately half of that previously derived from fossil calibration, and
      this has implications for our understanding of demographic events in human
      evolution and other aspects of population genetics. Here, we discuss the
      implications of a lower-than-expected mutation rate in relation to the timescale
      of human evolution.

PMID- 22965355
TI  - Genetic and epigenetic stability of human pluripotent stem cells.
AB  - Studies using high-resolution genome-wide approaches have recently reported that
      genomic and epigenomic alterations frequently accumulate in human pluripotent
      cells. Detailed characterization of these changes is crucial for understanding
      the impact of these alterations on self-renewal and proliferation, and
      particularly on the developmental and malignant potential of the cells. Such
      knowledge is required for the optimized and safe use of pluripotent cells for
      therapeutic purposes, such as regenerative cellular therapies using
      differentiated derivatives of pluripotent cells.In this Review, we summarize the
      current knowledge of the genomic and epigenomic stability of pluripotent human
      cells and the implications for stem cell research.

PMID- 22965357
TI  - Disease genetics: reporting on stability.

PMID- 22965359
TI  - Bonus? No, just an onus.

PMID- 22965356
TI  - The telomere syndromes.
AB  - There has been mounting evidence of a causal role for telomere dysfunction in a
      number of degenerative disorders. Their manifestations encompass common disease
      states such as idiopathic pulmonary fibrosis and bone marrow failure. Although
      these disorders seem to be clinically diverse, collectively they comprise a
      single syndrome spectrum defined by the short telomere defect. Here we review the
      manifestations and unique genetics of telomere syndromes. We also discuss their
      underlying molecular mechanisms and significance for understanding common age
      related disease processes.

PMID- 22965360
TI  - The concept of heart team in cardiac diseases: the patient is back as a priority
      in medical decisions.

PMID- 22965361
TI  - Association between human leukocyte antigens and graft-versus-host disease
      occurrence after allogenic hematopoietic stem cell transplantation.
AB  - CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the
      complications following allogenic stem cell transplantation. This study
      investigated an association between human leukocyte antigen (HLA) and the
      occurrence of acute and chronic GVHD in patients who had received stem cell
      transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective
      study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas
      (Unicamp). METHODS: The participants were 176 patients whose first transplant was
      between 1997 and 2009. HLA genotyping was performed serologically and using the
      polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was
      positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P =
      0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333)
      was more frequent in patients without acute GVHD. Chronic GVHD was positively
      associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2
      (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55
      (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in
      other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24
      (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA
      A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence
      the incidence and severity of acute and chronic GVHD. However, a study with a
      better design and more patients will be needed to confirm these results.

PMID- 22965362
TI  - Prevalence of overweight preschool children in public day care centers: a cross
      sectional study.
AB  - CONTEXT AND OBJECTIVE: Brazil is undergoing a period of epidemiological
      transition associated with demographic and nutritional changes. The prevalence of
      obesity is also increasing in children and is causing numerous health problems
      that are becoming public health issues. The aim here was to evaluate the
      prevalence of overweight among children of two and three years of age. DESIGN AND
      SETTING: Cross-sectional study in municipal day care centers in Taubate, state of
      Sao Paulo, Brazil. METHODS: Weight and height measurements were made on 447
      preschool children forming a probabilistic randomized sample. Their body mass
      index (BMI) was calculated. Their nutritional status was classified using the
      World Health Organization reference cutoff points (2006). Their mean weight,
      height and BMI were compared according to their age and sex. RESULTS: The mean
      values for the final sample (n = 447) were as follows: mean age: 38.6 months (+/-
      3.5) and Z scores for: weight/height (W/H): 0.50 (+/- 1.22); height/age: -0.03
      (+/- 1.07); weight/age (W/A): 0.51 (+/- 1.23); and BMI: 0.51(+/- 1.23). The
      prevalence of overweight children (BMI > 1 z) was 28.86%, while the prevalence of
      underweight children (BMI < -2 z) was 0.89%. There were no differences in mean
      BMI among the two and three-year age groups (P = 0.66). CONCLUSION: A high
      prevalence of overweight was observed in the sample of two and three-year-old
      children, with practically no malnutrition, thus showing that a significant
      nutritional transition may already be occurring, even in medium-sized cities of
      developing countries.

PMID- 22965363
TI  - Epidemiological and serological aspects of hepatitis A among children and
      teenagers in the city of Santos: a cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Viral hepatitis A is still a concern at public health
      level in Brazil and around the world, due both to the number of affected subjects
      and the possibility of complications in the acute forms. The Brazilian Ministry
      of Health estimates that at least 70% of this country's population has already
      had contact with the hepatitis A virus (HAV). The aim here was to discover the
      prevalence of serological markers for the hepatitis A virus among children and
      teenagers at daycare facilities, kindergartens and elementary schools in the city
      of Santos. DESIGN AND SETTING: Cross-sectional study in kindergartens and
      elementary schools within the municipal education network in several regions of
      the city of Santos. METHOD: Students' family members were surveyed using a
      questionnaire and 4,680 finger-prick blood samples were taken and assayed by
      means of the ELISA technique. RESULTS: The general prevalence of anti-HAV IgG was
      9.72% and, of these cases, 74.6% were reactive to anti-HAV IgM. There was higher
      prevalence of anti-HAV IgG among older children, females, children who played in
      streams, those whose homes were not connected to the sewage system, those whose
      parents had low education levels, those with low household income and those who
      did not live along the seashore. The prevalence of anti-HAV IgM peaked in the
      early years and subsequently fell, and it was lower on the hills and in the
      Northwestern Zone. CONCLUSION: The general prevalence of serological markers for
      hepatitis A was low in Santos.

PMID- 22965364
TI  - Cephalometric evaluation of the airway space and hyoid bone in children with
      normal and atypical deglutition: correlation study.
AB  - CONTEXT AND OBJECTIVE: Although there is a close relationship between swallowing
      and breathing, there are no studies evaluating the radiographic anatomy of the
      airway and its possible correlation with the radiographic position of the hyoid
      bone. The aim of this study was to evaluate the possible correlation of the
      radiographic position of the hyoid bone and airway space (PAS) in lateral
      radiographs on children with atypical deglutition, in comparison with those with
      normal swallowing. DESIGN AND SETTING: Cross-sectional analytical study with
      control group in a public university. METHODS: Using cephalometric analysis on
      lateral teleradiographs, the distance from the hyoid bone to the mandibular plane
      (MP-H) and the distance from the hyoid bone to the tuber (T-H) were correlated
      with the PAS measurement (airway) in two groups: 55 teleradiographs in the
      experimental group (with atypical deglutition) and 55 teleradiographs in the
      control group (normal deglutition). Both groups included subjects at the mixed
      dentition stage. RESULTS: The variable T-H presented a statistically significant
      correlation with PAS (0.0286) and the variable MP-H had a significant correlation
      with the variable PAS (0.0053). This positive correlation was significant only in
      the control group and not in the group with atypical swallowing. CONCLUSIONS:
      There was a positive correlation between the MP-H and PAS measurements and
      between the T-H and PAS measurements only in the group with normal swallowing.
      These correlations were not observed in the group with atypical swallowing.

PMID- 22965365
TI  - Association between maternal and fetal weight gain: cohort study.
AB  - CONTEXT AND OBJECTIVE: Excessive gestational weight gain is related to many
      complications (both maternal and fetal), such as macrosomia. The most common
      complications in macrosomic fetuses include: increased risk of intrauterine
      death, need for intensive care, fractures, neonatal hyperbilirubinemia, paralysis
      of the brachial plexus and obesity in childhood and adulthood. The aim of this
      study was to evaluate the association between gestational and fetal weight gain
      and the incidence of macrosomia in two maternity hospitals. DESIGN AND SETTING:
      Cohort study in two public maternity hospitals in Goiania, Brazil. METHODS: This
      was a cohort study on 200 healthy pregnant women with normal body mass index,
      divided into two groups: one with normal weight gain and the other with excessive
      weight gain during pregnancy. RESULTS: The cohorts were similar regarding
      maternal age, per capita income, schooling level and reproductive behavior. The
      fetal weight was greater in the cohort with excessive maternal weight gain
      (3,388.83 g +/- 514.44 g) than in the cohort with normal weight (3,175.86 g +/-
      413.70 g) (P < 0.01). The general incidence of macrosomia was 6.5%: 13.0% (13
      cases) in the cohort with excessive maternal weight gain and 0.0% (0 cases) in
      the cohort with adequate weight gain. CONCLUSION: Excessive maternal weight gain
      was associated with increased fetal birth weight and incidence of macrosomia.

PMID- 22965366
TI  - Molecular characterization of hemoglobin D Punjab traits and clinical
      hematological profile of the patients.
AB  - CONTEXT AND OBJECTIVE: Hemoglobin (Hb) D hemoglobinopathies are widespread
      diseases in northwestern India and usually present with mild hemolytic anemia and
      mild to moderate splenomegaly. The heterozygous form of Hb D is clinically
      silent, but coinheritance of Hb D with Hb S or beta-thalassemia produces
      clinically significant conditions like thalassemia intermedia of moderate
      severity. Under heterozygous conditions with coinheritance of alpha and beta
      thalassemia, patients show a degree of clinical variability. Thus, our aim was to
      molecularly characterize the Hb D trait among individuals who were clinically
      symptomatic because of co-inheritance of alpha deletions or any beta-globin gene
      mutations. DESIGN AND SETTING: This was a cross-sectional study conducted in an
      autonomous tertiary-care hospital. METHODS: Complete blood count and red cell
      indices were measured using an automated cell analyzer. Quantitative assessment
      of hemoglobin Hb F, Hb A, Hb A2 and Hb D was performed by means of high
      performance liquid chromatography (HPLC). DNA extraction was done using the
      phenol-chloroform method. Molecular analyses on common alpha deletions and common
      beta mutations were done using the Gap polymerase chain reaction and
      Amplification Refractory Mutation System, respectively. RESULTS: We evaluated 30
      patients and found clinical variation in the behavior of Hb D traits. In six
      patients, the Hb D traits were clinically symptomatic and behaved like those of
      thalassemia intermedia. Molecular characterization showed that three out of these
      six were IVS-1-5 positive. CONCLUSIONS: HPLC may not be the gold standard for
      diagnosing symptomatic Hb D Punjab traits. Hence, standard confirmation should
      include molecular studies.

PMID- 22965367
TI  - Mentors also need support: a study on their difficulties and resources in medical
      schools.
AB  - CONTEXT AND OBJECTIVE: Mentors have been recognized as important elements in the
      personal and professional development of medical students. However, few
      investigations have sought to understand their development, needs and
      difficulties. Our objective was to investigate the perceptions of a group of
      mentors regarding difficulties experienced over time and the resources used to
      face up to them. DESIGN AND SETTING: Qualitative exploratory study on mentors at
      Faculdade de Medicina da Universidade de Sao Paulo (FMUSP). In the FMUSP
      Mentoring Program, mentors follow and guide students throughout the course, and
      are responsible for heterogeneous group of students, in relation to the academic
      year. METHOD: Semi-structured interviews were conducted with 14 FMUSP mentors.
      RESULTS: For many of the mentors, the difficulties related to initial doubts
      about the role, frustration with the students' attendance and overloading of
      daily tasks. To address such difficulties, these mentors used external resources
      and their own life experience and personal way of dealing with situations. Some
      mentors did not perceive difficulties for themselves or for students.
      CONCLUSIONS: Like in other mentoring programs, many difficulties perceived by
      mentors seem to be derived from the context of medical education itself. However,
      unlike in other experiences, FMUSP mentors do not feel that there is lack of
      support for their role, since this is regularly provided in the structure and
      dynamics of the program. The "difficulty in perceiving difficulties", presented
      by some mentors, demands further investigation for better and greater
      understanding.

PMID- 22965368
TI  - Subacute combined spinal cord degeneration and pancytopenia secondary to severe
      vitamin B12 deficiency.
AB  - CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical
      or hematological abnormalities. Subacute combined spinal cord degeneration and
      pancytopenia are two serious and rarely displayed consequences that appear in
      severe deficits. CASE REPORT: We present the case of a patient with subacute
      combined spinal cord degeneration and pancytopenia secondary to severe and
      sustained vitamin B12 deficiency. Such cases are rare nowadays and have
      potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be
      taken into consideration in the differential diagnosis in cases of blood
      disorders or severe neurological symptoms. Early diagnosis and treatment can
      avoid irreversible consequences.

PMID- 22965369
TI  - Leukocyte adhesion deficiency syndrome: report on the first case in Chile and
      South America.
AB  - CONTEXT: Adhesion molecule deficiency type 1 is a rare disease that should be
      suspected in any patient whose umbilical cord presents delay in falling off, and
      who presents recurrent severe infections. Early diagnostic suspicion and early
      treatment improve the prognosis. CASE REPORT: The case of a four-month-old boy
      with recurrent hospitalizations because of severe bronchopneumonia and several
      episodes of acute otitis media with non-purulent drainage of mucus and positive
      bacterial cultures is presented. His medical history included neonatal sepsis and
      delayed umbilical cord detachment. Laboratory studies showed marked leukocytosis
      with predominance of neutrophils and decreased CD11b and CD18. These were all
      compatible with a diagnosis of leukocyte adhesion deficiency type I [LAD type 1].

PMID- 22965370
TI  - Drugs available through the Farmacia Dose Certa program and Beers criteria: a
      further analysis.

PMID- 22965374
TI  - Sun belt rising: regional population change and the decline in black residential
      segregation, 1970-2009.
AB  - The goal of this study is to examine the extent to which population shifts over
      the post-Great Migration period and divergent trends in segregation across
      regions contributed to the overall decline in black segregation in the United
      States in recent decades. Using data from the 1970 to 2000 decennial censuses and
      the 2005-2009 American Community Survey (ACS), our analysis indicates that black
      dissimilarity and isolation declined more in the South and West than in the
      Northeast and Midwest. Nevertheless, regional population shifts account for only
      a modest amount (8 % to 12 %) of the decline in black-white segregation over the
      period and for an even smaller proportion of the decline in black-nonblack
      segregation, in part because the largest declines in segregation occurred in the
      West while the region with the largest relative increase in the black population
      was the South. Using more refined census divisions rather than census regions
      provided some additional explanatory power (shifts across divisions explained 15
      %-16 % of the decline in black-white segregation): divisions with larger gains in
      their share of the black population tended to have larger declines in black
      segregation. Overall, although the effect of the regional redistribution of the
      black population on declines in segregation was significant, of even greater
      importance were other causes of substantial declines in segregation in a wide
      array of metropolitan areas across the country, and especially in the West, over
      the past 40 years.

PMID- 22965375
TI  - Population trends as a counterweight to central city decline, 1950-2000.
AB  - The share of metropolitan residents living in central cities declined
      dramatically from 1950 to 2000. We argue that cities would have lost even further
      ground if not for demographic trends such as renewed immigration, delayed
      childbearing, and a decline in the share of households headed by veterans. We
      provide causal estimates of the effect of children on residential location using
      the birth of twins. The effect of veteran status is identified from a
      discontinuity in the probability of military service during and after the mass
      mobilization for World War II. Our results suggest that these changes in
      demographic composition were strong enough to bolster city population but not to
      fully counteract socioeconomic factors favoring suburban growth.

PMID- 22965376
TI  - Your place or mine? On the residence choice of young couples in Norway.
AB  - Norwegian registry data are used to investigate the location decisions of a full
      population cohort of young adults as they complete their education, establish
      separate households, and form their own families. We find that the labor market
      opportunities and family ties of both partners affect these location choices.
      Surprisingly, married men live significantly closer to their own parents than do
      married women, even if they have children, and this difference cannot be
      explained by differences in observed characteristics. The principal source of
      excess female distance from parents in this population is the relatively low
      mobility of men without a college degree, particularly in rural areas. Despite
      evidence that intergenerational resource flows, such as childcare and eldercare,
      are particularly important between women and their parents, the family
      connections of husbands appear to dominate the location decisions of less
      educated married couples.

PMID- 22965377
TI  - Beneficial effects of combination therapy of intradialytic parenteral nutrition
      and oral L-carnitine administration.

PMID- 22965379
TI  - Value of routine frozen section analysis of urethral margin in male patients
      undergoing radical cystectomy in predicting prostatic involvement.
AB  - PURPOSE: To prospectively investigate diagnostic value of routine frozen section
      analysis (FSA) of urethral margin for male patients undergoing cystectomy for
      bladder cancer. MATERIALS AND METHODS: One hundred consecutive male patients were
      subjected to radical cystectomy for bladder cancer with routine FSA obtained from
      distal prostatic urethral margin. Definitive pathological condition of the
      specimens was reviewed to diagnose urethral+/-prostatic malignant involvement.
      The diagnostic value of FSA was identified and compared with different clinical
      and pathological predictors. Patients with false-negative results were followed
      for 5 years. RESULTS: Six patients showed evidence of malignancy by FSA of the
      prostatic urethral margin (one patient was false positive), and all were managed
      by urethrectomy. Prostatic +/- urethral involvement was diagnosed in 15 patients
      by definitive histopathology (15%). Sensitivity and specificity of urethral
      margin frozen section were 33.3 and 98.8%, respectively, with overall accuracy of
      89% while positive and negative predictive values were 83.3 and 89.4%,
      respectively. There was no significant correlation identified between tumor site
      or morphology, clinical staging, clinically suspicious prostate, cystoscopic
      involvement of bladder neck, tumor grade, and associated carcinoma in situ or
      nodal involvement with prostatic malignant involvement. Positive intraoperative
      FSA was the only predictor significantly associated with malignant urothelial
      involvement of the prostate. None of the 10 patients with false-negative results
      developed late urethral recurrence at 5 years. CONCLUSION: Intraoperative
      urethral frozen section shows high predictive diagnostic value of malignant
      prostatic involvement. Nevertheless, its impact in preventing late urethral
      recurrence is doubtful.

PMID- 22965378
TI  - Cardiovascular risk biomarkers in CKD: the inflammation link and the road less
      traveled.
AB  - End-stage renal disease patients suffer a syndrome of accelerated aging
      characterized by a 10- to 100-fold increase in cardiovascular and all-cause
      mortality when compared to age-matched controls. No specific therapeutic
      interventions have been shown to improve this dismal outcome. Inflammation,
      chronic kidney disease-mineral and bone disorder (CKD-MBD) and other biomarkers
      predict outcome in observational studies. However, we lack clinical trials that
      address the role of these biomarkers in risk stratification and therapeutic
      decision making. Biomarkers may also provide insights into the pathophysiology of
      disease and identify novel therapeutic targets. Inflammation emerges as a prime
      potential target for intervention. Thus, CKD-MBD biomarkers, asymmetrical
      dimethyl arginine and tri-iodothyronine have a link to inflammation. Interleukin
      6 (IL-6) is one of the inflammation biomarkers with highest predictive value for
      outcome in ESRD. Biologicals targeting IL-6 are approved for the treatment of
      chronic inflammatory conditions such as rheumatoid arthritis. Furthermore, trials
      are underway to test IL-6 targeting potential to decrease cardiovascular injury
      in non-CKD patients. In this regard, targeting IL-1 was recently shown to
      decrease systemic inflammation in hemodialysis patients. The success of these
      trials will likely influence future studies on biomarker targeting in CKD.

PMID- 22965381
TI  - The degree of articular depression as a predictor of soft-tissue injuries in
      tibial plateau fracture.
AB  - PURPOSE: Magnetic resonance imaging (MRI) provides sufficient information with
      regard to specific soft-tissue injuries in the knee, but it is not generally used
      to evaluate acute tibial plateau fractures. The aim of the present study was to
      determine whether the amount of tibial plateau fracture depression on multi
      detector computed tomography (MDCT) scans correlates with the incidence of
      associated soft-tissue injuries on MRI. METHODS: A total of 54 consecutive
      patients with a mean age of 51.2 years (SD = 18.3) were included in this
      retrospective study. All patients were admitted to the emergency department of a
      university clinic with acute tibial plateau fracture. The amount of articular
      depression was assessed from MDCT scans. Magnetic resonance images were evaluated
      for crucial and collateral ligament injury, meniscal tears, and patellar
      retinaculum lesions. RESULTS: Logistic regression revealed a significant impact
      of increasing tibial plateau fracture depression on the incidence of meniscus
      lateralis tears (P = 0.025) and anterior cruciate ligament lesions (P = 0.018).
      Analysis of covariance demonstrated a significant correlation between the amount
      of articular depression and absolute number of soft-tissue injuries (P = 0.001).
      CONCLUSIONS: Articular depression is a potential predictor of specific meniscal
      and ligamentous injuries in acute tibial plateau fracture. Magnetic resonance
      imaging is generally recommended with respect to associated soft-tissue injuries,
      especially in cases with distinct tibial plateau fracture depression on multi
      detector computed tomography scans. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 22965380
TI  - Sagittal alignment of the cervical spine in adolescent idiopathic scoliosis
      treated by posteromedial translation.
AB  - PURPOSE: To analyze postoperative changes in the cervical sagittal alignment
      (CSA) of patients with AIS treated by posteromedial translation. METHODS: 49
      patients with thoracic AIS underwent posterior arthrodesis with hybrid
      constructs, combining lumbar pedicle screws and thoracic universal clamps.
      Posteromedial translation was the main correction technique used. 3D radiological
      parameters were measured from low-dose biplanar radiographs. CSA was assessed
      using the C2C6 angle, and the central hip vertical axis (CHVA) was used as a
      reference axis to evaluate patients' balance. RESULTS: Preoperatively, 58 % of
      patients had thoracic hypokyphosis, and 79 % had a kyphotic CSA. Significant
      correlation was found (r = 0.45, P = 0.01) between thoracic hypokyphosis and
      cervical kyphosis. Increase in T4-T12 thoracic kyphosis (average 14.5 degrees  +/
      10 degrees ) was associated with significant decrease in cervical kyphosis in
      the early postoperative period. The CSA further improved spontaneously during
      follow-up by 7.6 degrees  (P < 0.0001). Significant positive correlation (r =
      0.32, P = 0.03) was found between thoracic and cervical improvements. At latest
      follow-up, 94 % of the patients were normokyphotic and 67 % had a CSA in the
      physiological range. Sagittal balance of the thoracolumbar spine was not
      significantly modified postoperatively. However, the procedure significantly
      changed the position of C2 in regard to the CHVA (C2-CHVA), which reflects
      headposition (P = 0.012). At last follow-up, the patients sagittal imbalance was
      not significantly different from the preoperative imbalance (P = 0.34).
      CONCLUSIONS: Thoracic hypokyphosis and cervical hypolordosis, observed in AIS,
      can be improved postoperatively, when the posteromedial translation technique is
      used for correction. The cervical spine remains adaptable in most patients, but
      the proportion of patients with physiological cervical lordosis at final follow
      up remained low (24.5 %).

PMID- 22965382
TI  - In vitro osteoclast-like and osteoblast cells' response to electrospun calcium
      phosphate biphasic candidate scaffolds for bone tissue engineering.
AB  - Successful long term bone replacement and repair remain a challenge today.
      Nanotechnology has made it possible to alter materials' characteristics and
      therefore possibly improve on the material itself. In this study, biphasic
      hydroxyapatite/beta-tricalcium phosphate nanobioceramic scaffolds were prepared
      by the electrospinning technique in order to mimic the extracellular matrix.
      Scaffolds were characterised by scanning electron microscopy (SEM) and attenuated
      total reflectance-fourier transform infrared. Osteoblasts as well as monocytes
      that were differentiated into osteoclast-like cells, were cultured separately on
      the biphasic bioceramic scaffolds for up to 6 days and the proliferation,
      adhesion and cellular response were determined using lactate dehydrogenase
      cytotoxicity assay, nucleus and cytoskeleton dynamics, analysis of the cell cycle
      progression, measurement of the mitochondrial membrane potential and the
      detection of phosphatidylserine expression. SEM analysis of the biphasic
      bioceramic scaffolds revealed nanofibers spun in a mesh-like scaffold. Results
      indicate that the biphasic bioceramic electrospun scaffolds are biocompatible and
      have no significant negative effects on either osteoblasts or osteoclast-like
      cells in vitro.

PMID- 22965383
TI  - Prosthetic limb salvage surgery for bone and soft tissue tumors around the knee.
AB  - In this study, we analyzed long-term survival, limb function and associated
      complications after prosthetic limb salvage treatment in patients with bone and
      soft tissue tumors around the knee joint. A total of 63 patients treated with
      prosthetic limb salvage surgery around the knee were reviewed. The bone tumors
      involved the distal femur in 45 patients, the proximal tibia in 14 patients and
      the soft tissue tumors of the proximal lower leg in 4 patients. The median follow
      up period after the first operation was 8.0 years. The medical records of the
      patients, surgical reports, radiographs and histological specimens were
      retrospectively reviewed. The 5-year overall survival rate was 63.2% in the
      patients with distal femur tumors and 86.2% in those with tumors of the proximal
      lower leg. The 5-year prosthetic survival rate was 72.8% in the distal femur and
      74.6% in the proximal lower leg. The mean functional score according to the
      scoring system of the Musculoskeletal Tumor Society (MSTS) was 81% in the
      patients with distal femur tumors and 82% in the patients with proximal lower leg
      tumors. Post-operative complications occurred in 27 patients. Limb salvage
      surgery is considered to be an effective treatment option. However, the high
      complication rate is a major concern for prosthetic replacement. Future
      improvements of prostheses are very important.

PMID- 22965390
TI  - Advance care planning of the acutely unwell patient.

PMID- 22965392
TI  - Too sweet to be real?

PMID- 22965394
TI  - Sitting time and all-cause mortality risk.

PMID- 22965395
TI  - It is also what you do when sitting.

PMID- 22965396
TI  - Is sitting harmful to health? It is too early to say.

PMID- 22965398
TI  - Magnetically recyclable nanocatalysts (MRNCs): a versatile integration of high
      catalytic activity and facile recovery.
AB  - Recent advances in wet chemical synthesis of magnetically recyclable
      nanocatalysts (MRNCs), a versatile integration of high catalytic activity and
      facile recovery, have led to a dramatic expansion of their potential
      applications. This review focuses on the recent work in the development of metal
      and metal oxide based MRNCs for catalytic conversion of organic compounds in
      solution phase. This will be discussed in detail, according to the two main
      synthesis methods of MRNCs as classified by us. The two methods are: template
      assisted synthetic strategy and direct synthetic strategy. And the template
      assisted synthesis is further divided into three subcategories, synthetic
      strategies assisted by hard-, soft-, and mixed hard-soft coupling layers. At the
      end, we outline future trends and perspectives in these research areas.

PMID- 22965399
TI  - Cost-effectiveness of laparoscopic vs open resection for colon and rectal cancer.
AB  - BACKGROUND: Whether laparoscopic surgery for colon and rectal cancer is cost
      effective in comparison with open surgery remains unclear, because laparoscopic
      surgery results in shorter hospital stays but is associated with increased
      equipment costs. OBJECTIVE: This study aimed to investigate the cost
      effectiveness of laparoscopic versus open surgery for colon and rectal cancer,
      incorporating factors not included in previous cost-effectiveness studies.
      DESIGN: A decision analysis model was constructed, and extensive sensitivity
      analyses were performed to test the assumptions of the model. SETTING: Data were
      taken from previously published studies; data from large randomized trials were
      used whenever possible as inputs into the model. PATIENTS: Patients enrolled in
      the trials from which data were gathered for the model. INTERVENTIONS: There were
      no interventions. MAIN OUTCOME MEASURES: The primary outcome measured was the
      cost-effectiveness of laparoscopic versus open surgery for colon and rectal
      cancer, expressed as cost per quality-adjusted life-year. RESULTS: Laparoscopic
      resection results in savings of $4283 and essentially no difference in quality
      adjusted life-years (0.001 more quality-adjusted life-years than open resection).
      Sensitivity analyses indicate that laparoscopic surgery is cost-effective at
      <$50,000 per quality-adjusted life-year under almost all conditions. The only
      circumstance that affects the cost-effectiveness of laparoscopic surgery is
      postoperative hernia rates. Because of the additional time off work for hernia
      repair, laparoscopic resection is cost-effective only if it results in a hernia
      rate less than or equal to open surgery. For all other variables, the
      laparoscopic approach remains less costly than the open approach with no
      difference in quality of life. LIMITATIONS: The model relies on data from other
      studies, rather than being an independent trial designed to specifically collect
      these data. CONCLUSIONS: Laparoscopic resection for colon and rectal cancer
      results in decreased costs and equivalent quality of life, making it the
      preferred approach in suitable patients.

PMID- 22965400
TI  - Oncologic outcome after preoperative chemoradiotherapy in patients with
      pathologic T0 (ypT0) rectal cancer.
AB  - BACKGROUND: Little is known about the oncologic outcomes of patients with ypT0
      rectal cancer after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the
      clinicopathologic characteristics and oncologic outcomes of patients with ypT0
      rectal cancer after preoperative chemoradiotherapy and curative radical surgery.
      DESIGN AND SETTINGS: This was a retrospective review of factors influencing
      outcome of patients treated with preoperative chemoradiotherapy for rectal cancer
      at a tertiary care university medical center in Seoul, Korea between 2000 and
      2008. PATIENTS: A total of 830 rectal cancer patients underwent surgery after
      preoperative chemoradiotherapy. Patients were included in the study if they had a
      pretreatment clinical classification of T3-4 or N+ (or T2N0 and preoperative
      chemoradiotherapy for sphincter preservation) and if they were classified on
      pathologic examination as ypT0 after preoperative CRT and curative radical
      surgery. Patients were classified as. MAIN OUTCOME MEASURES: Overall survival and
      disease-free survival were evaluated in relation to ypT0N0 or ypT0N1-2 status and
      other factors that might influence outcome. RESULTS: Of 91 patients included in
      the study, 54 (59.3%) were men; the mean patient age was 55 (SD, 11) years, and
      mean follow-up duration was 44 (SD, 23) months. Surgical procedures included low
      anterior resection in 68 patients, abdominoperineal resection in 21, and
      intersphincteric resection in 2. Mean tumor distance from the anal verge was 4.7
      (SD, 1.8) cm. Of the 91 patients, 85 were classified as ypT0N0 and 6 as ypT0N1-2.
      No patient experienced local recurrence. A total of 11 patients (12.1%) had
      distant metastases, after a mean 11.1 months, including 7 (8.2%) with ypT0N0 and
      4 (66.7%) with ypT0N1-2 tumors. One patient with ypT0N0 and 2 patients with
      ypT0N1-2 tumors died of metastasis. In patients classified as ypT0N0, the 5-year
      disease free survival and overall survival rates were 82.3% and 89.2%,
      respectively. Multivariate analysis showed that ypN1-2 status (p = 0.001) was a
      significant independent risk factor for recurrence (decreased 5-year disease-free
      survival), but no factor was associated with 5-year overall survival.
      LIMITATIONS: The study is limited by its retrospective nature. CONCLUSION:
      Oncologic outcomes in patients with ypT0N0 rectal cancer were excellent. The
      presence of residual cancer cells in mesorectal lymph nodes represents a risk
      factor for distant metastasis.

PMID- 22965401
TI  - Can combined 18F-FDG-PET and dynamic contrast-enhanced MRI predict behavior of
      desmoid tumors in patients with familial adenomatous polyposis?
AB  - BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis show
      variable behavior; about 10% grow relentlessly, resulting in severe morbidity or
      mortality. Investigations that could identify the minority of desmoid tumors that
      behave aggressively would allow these tumors to be treated early and spare the
      majority of patients who have more benign disease from unnecessary intervention.
      OBJECTIVE: The aim of this study was to investigate whether imaging the tumor
      metabolic-vascular phenotype by modern methods predicts growth. DESIGN: This is a
      prospective case series study. SETTINGS: The study was conducted at a tertiary
      center specializing in familial adenomatous polyposis and desmoid disease.
      PATIENTS: Nine patients with familial adenomatous polyposis (4 male, mean age 39
      years) with desmoid tumor underwent 18F-FDG-PET and dynamic contrast-enhanced
      MRI. Standard MRI was repeated a year later to assess tumor growth. MAIN OUTCOME
      MEASURES: The primary outcome measured was the correlation between 18F-FDG-PET
      and dynamic contrast-enhanced MRI parameters and subsequent desmoid growth.
      RESULTS: Failed intravenous access precluded dynamic contrast-enhanced MRI in 1
      female patient. Thirteen desmoid tumors (4 intra-abdominal, 2 extra-abdominal, 7
      abdominal wall; mean area, 68 cm) were analyzed in the remaining 8 patients. Two
      patients died before follow-up MRI. Five tumors decreased in size, 3 increased in
      size, and 3 remained stable after a year. Significant correlation (Spearman rank
      correlation, significance at 5%) existed between maximum standardized uptake
      value and k(ep) (r = -0.56, p = 0.04), but not with other vascular parameters
      (K(trans) (r = -0.47, p = 0.09); v(e) (r = -0.11, p = 0.72); integrated area
      under the gadolinium-time curve at 60 seconds (r = -0.47, p = 0.10)). There was
      no significant difference in the maximum standardized uptake value or dynamic
      contrast-enhanced MRI parameters (K(trans), v(e), k(ep), integrated area under
      the gadolinium-time curve at 60 seconds) between the tumors that grew or
      decreased in size or between the tumor sites. However, vascular metabolic ratio
      (maximum standardized uptake value/K(trans)) was significantly different for
      tumor site (p = 0.001) and size (p = 0.001, 1-way ANOVA). LIMITATIONS: This
      investigation is limited because of its exploratory nature and small patient
      numbers. CONCLUSIONS: Although not predictive for tumor behavior, some
      correlations existed between dynamic contrast-enhanced MRI and 18F-FDG-PET
      parameters. Vascular metabolic ratio may provide further information on tumor
      behavior; however, this needs to be evaluated with further larger studies.

PMID- 22965402
TI  - Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term
      outcome.
AB  - BACKGROUND: Juvenile polyposis syndrome is phentoypically and genotypically
      heterogeneous. It is associated with an increased risk of GI cancers, and
      surveillance is recommended. Few data exist that detail the outcomes of
      surveillance in juvenile polyposis syndrome. OBJECTIVE: The aim of this study was
      to review clinical features, genetic mutations, and long-term outcome data in
      patients with juvenile polyposis syndrome. DESIGN: This study is a retrospective
      review. SETTING: The Polyposis Registry, St Mark's Hospital, was used in the
      performance of this study. PATIENTS: Patients with juvenile polyposis syndrome
      who were followed up at our institution were included. RESULTS: Forty-four
      patients (27 male) from 30 kindreds were included. Fifteen were diagnosed by
      screening, and 29 presented symptomatically. Nineteen patients had SMAD4 mutation
      and 9 had BMPR1A mutation. Five patients (11%) had valvular heart disease.
      Telangiectasia/vascular abnormalities were observed in 4 (9%) patients, and
      macrocephaly was observed in 5 (11%). Six patients (14%) developed cancer; 4 had
      cancer at the time of diagnosis of juvenile polyposis syndrome, 3 developed
      cancer while on surveillance (1 patient had a second primary). All patients with
      advanced upper GI disease had SMAD4 mutations. Where germline mutation was known,
      all patients with telangiectasia had SMAD4 mutation. Seven patients required GI
      surgery at our institution: colectomy and ileorectal anastomosis (1), restorative
      proctocolecotomy (1), anteroposterior excision for rectal cancer (1), gastrectomy
      (2), and laparotomy and intraoperative enteroscopy (1). There were no
      complications of endoscopic surveillance. Colonic polyps predominated; 535 of 767
      (69.8%) of colonic polyps were right sided. One patient had a solitary
      significant small-bowel polyp. Sixty-five juvenile polyps contained dysplasia
      (mild to moderate). Two patients had severe dysplasia or cancer found in
      carpeting polyps. LIMITATIONS: This is a retrospective review. The cohort size,
      although modest, is good for such a rare condition. CONCLUSION: Extraintestinal
      features are common. Gastrointestinal surveillance is safe. Most colonic polyps
      are right sided, and detecting dysplasia is uncommon. Carpeting polyps are of
      particular concern.

PMID- 22965403
TI  - Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for
      colorectal and appendiceal carcinomatosis.
AB  - BACKGROUND: Delayed repeated intraperitoneal chemotherapy after cytoreductive
      surgery for carcinomatosis may be an alternative to intraoperative hyperthermic
      infusion. OBJECTIVE: The aim of this study was to evaluate the safety and
      feasibility of delayed repeated intraperitoneal chemotherapy after cytoreduction
      of colorectal and appendiceal carcinomatosis and pseudomyxoma peritonei. DESIGN:
      This study constitutes a retrospective case series. SETTING: This study was
      conducted at a single institution. PATIENTS: A total of 31 patients with
      peritoneal carcinomatosis (23) and pseudomyxoma peritonei (8) were included.
      INTERVENTIONS: Cytoreduction was followed by placement of an adhesion barrier and
      intraperitoneal catheters. Peritoneal scintigraphy preceded biweekly
      intraperitoneal 5-fluorouracil and systemic combination chemotherapy with
      leucovorin, fluorouracil, and oxaliplatin (FOLFOX). MAIN OUTCOME MEASURES: The
      primary outcomes measured are safety, feasibility, and short-term survival.
      RESULTS: Cytoreduction to a score of 0 to 1 was possible in 25 patients (80%).
      Complications occurred in 16 patients (51.6%) and were confined to grades I to
      III. There were no deaths, and no digestive fistulae occurred. Port malfunction
      or complication resulted in removal in 5 patients (16.1%). Intraperitoneal
      chemotherapy was possible in 83.8% of patients; 55% completed the full course.
      Peritoneal scintigraphy demonstrated free diffusion of tracer in 18 patients
      (58%), 4 (12.9%) had diffusion in each gutter with limited communication, 5
      (16.1%) had limited diffusion around each catheter without communication, and 2
      (6.5%) had no diffusion on scintigraphy. Overall survival for peritoneal
      carcinomatosis was 44.5% at 3 years (95% CI = 23%-65%). LIMITATIONS: The
      nonrandomized nature of this study and the early experience are limitations.
      CONCLUSIONS: Delayed repeated intraperitoneal and systemic chemotherapy after
      cytoreduction is feasible and has acceptable morbidity rates. Delayed
      intraperitoneal chemotherapy is possible in 83% of patients.

PMID- 22965404
TI  - A randomized controlled trial comparing colonic irrigation and oral antibiotics
      administration versus 4% formalin application for treatment of hemorrhagic
      radiation proctitis.
AB  - BACKGROUND: Several treatments have been described for hemorrhagic radiation
      proctitis. The treatment outcomes are variable. Colonic irrigation and oral
      antibiotics for hemorrhagic radiation proctitis have been recently reported to be
      a novel and promising therapeutic approach. However, a comparative study of this
      treatment has never been investigated. OBJECTIVE: This study aimed to compare
      colonic irrigation and oral antibiotics (irrigation group) versus 4% formalin
      application (formalin group) for treatment of hemorrhagic radiation proctitis.
      DESIGN: This was a randomized controlled trial. SETTING: This study was conducted
      in a tertiary care/university-based hospital. PATIENTS: Fifty patients with
      hemorrhagic radiation proctitis were randomly assigned to each treatment group (n
      = 25). INTERVENTIONS: For individuals allocated to the irrigation group, daily
      self-administered colonic irrigation with 1 L of tap water and a 1-week period of
      oral antibiotics (ciprofloxacin and metronidazole) were prescribed. For
      individuals allocated to the formalin group, 4% formalin application for 3
      minutes was performed. MAIN OUTCOME MEASURES: Patients' symptoms and the
      endoscopic findings of each group were collected. Patient satisfaction was
      surveyed. The outcomes were evaluated at 8 weeks after the initiation of
      treatment. RESULTS: There was a significant improvement in rectal bleeding and
      bowel frequency in both treatment groups, but significant improvement in urgency,
      diarrhea, and tenesmus was demonstrated only in the irrigation group. The
      comparative study between 2 treatments revealed greater improvement in rectal
      bleeding, urgency, and diarrhea in the irrigation group. Twenty of 24 patients in
      the irrigation group and 10 of 23 patients in the formalin group were satisfied
      with the treatment. LIMITATIONS: This trial cannot illustrate whether the
      antibiotics and the irrigation were equally important because of the limitation
      of a 2-armed design. CONCLUSIONS: The treatment with colonic irrigation and oral
      antibiotics appears to be more effective than 4% formalin application for
      hemorrhagic radiation proctitis treatment and achieves higher patient
      satisfaction.

PMID- 22965405
TI  - Fecal incontinence decreases sexual quality of life, but does not prevent sexual
      activity in women.
AB  - BACKGROUND: The impact of anal incontinence on women's sexual function is poorly
      understood. OBJECTIVE: The aim of this study was to investigate the relationship
      between anal incontinence and sexual activity and functioning in women. DESIGN:
      This is a cross-sectional study. SETTINGS: This investigation was conducted in a
      community-based integrated health care delivery system. PATIENTS: Included were
      2269 ethnically diverse women aged 40 to 80 years. MAIN OUTCOME MEASURES: Self
      administered questionnaires assessed accidental leakage of gas (flatal
      incontinence) and fluid/mucus/stool (fecal incontinence) in the past 3 months.
      Additional questionnaires assessed sexual activity, desire and satisfaction, as
      well as specific sexual problems (difficulty with arousal, lubrication, orgasm,
      or pain). Multivariable logistic regression models compared sexual function in
      women with 1) isolated flatal incontinence, 2) fecal incontinence (with or
      without flatal incontinence), and 3) no fecal/flatal incontinence, controlling
      for potential confounders. RESULTS: Twenty-four percent of women reported fecal
      incontinence and 43% reported isolated flatal incontinence in the previous 3
      months. The majority were sexually active (62% of women without fecal/flatal
      incontinence, 66% with isolated flatal incontinence, and 60% with fecal
      incontinence; p = 0.06). In comparison with women without fecal/flatal
      incontinence, women with fecal incontinence were more likely to report low sexual
      desire (OR: 1.41 (CI: 1.10-1.82)), low sexual satisfaction (OR: 1.56 (CI: 1.14
      2.12)), and limitation of sexual activity by physical health (OR: 1.65 (CI: 1.19
      2.28)) after adjustment for confounders. Among sexually active women, women with
      fecal incontinence were more likely than women without fecal/flatal incontinence
      to report difficulties with lubrication (OR: 2.66 (CI: 1.76-4.00)), pain (OR:
      2.44 (CI: 1.52-3.91)), and orgasm (OR: 1.68 (CI: 1.12-2.51)). Women with isolated
      flatal incontinence reported sexual functioning similar to women without
      fecal/flatal incontinence. LIMITATIONS: The cross-sectional design prevented
      evaluation of causality. CONCLUSIONS: Although most women with fecal incontinence
      are at high risk for several aspects of sexual dysfunction, the presence of fecal
      incontinence does not prevent women from engaging in sexual activity. This
      indicates that sexual function is important to women with anal incontinence and
      should be prioritized during therapeutic management.

PMID- 22965406
TI  - Transanal irrigation for bowel symptoms in patients with multiple sclerosis.
AB  - BACKGROUND: Constipation and fecal incontinence affect 68% of patients with
      multiple sclerosis, but management is empirical. Transanal irrigation has been
      used successfully in patients with neurogenic bowel dysfunction. OBJECTIVE: The
      aim of this study was to evaluate the effect of transanal irrigation on the bowel
      symptoms and general health status in these patients and the characteristics of
      those that had successful treatment and to obtain data for power calculations
      necessary for future randomized controlled studies. DESIGN: This was a
      prospective observational study in which pre- and posttreatment questionnaires
      (bowel symptoms and health status) were compared. Patients for whom treatment
      resulted in at least 50% improvement in bowel symptoms were considered
      responders. Baseline variables including anorectal physiology tests and rectal
      compliance were compared between responders and nonresponders. SETTINGS: This
      study was conducted at a specialist neurogastroenterology clinic, tertiary
      referral center. PATIENTS: Included were 30 patients who had multiple sclerosis
      and constipation, fecal incontinence, or both. INTERVENTION: Transanal irrigation
      was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the
      Wexner Constipation and Wexner Incontinence scores. The secondary outcomes was
      the SF-36 health survey. All scores were recorded before and after 6 weeks of
      treatment. RESULTS: At 6 weeks posttreatment, the Wexner Constipation score
      significantly improved (12 (8.75/16) pretreatment vs 8 (4/12.5) posttreatment, p
      = 0.001), as well as the Wexner Incontinence score (12 (4.75/16) pretreatment vs
      4 (2/8) posttreatment, p < 0.001). The SF-36 score did not improve significantly
      (51.3 +/- 7.8 pretreatment vs 50.4 +/- 7.8 posttreatment, p = 0.051). Sixteen
      patients were responders and had higher baseline Wexner Incontinence scores (14
      (11/20) responders vs 9 (4/15) nonresponders, p = 0.038) and SF-36 (53.9 +/- 6.3
      responders vs 47.9 +/- 7.8 nonresponders, p = 0.027), as well as greater maximum
      tolerated volume to rectal balloon distension (310 (220/320) mL responders vs 168
      (108/305) mL nonresponders, p = 0.017) and rectal compliance (15.2 (14.5/17.2)
      mL/mmHg responders vs 9.2 (7.2/15.3) mL/mmHg nonresponders, p = 0.019).
      LIMITATIONS: This study was limited by its small sample size and the lack of
      control group with alternative treatment. CONCLUSIONS: Transanal irrigation is
      effective to treat bowel symptoms in patients with multiple sclerosis. Responders
      (53%) had higher baseline incontinence symptoms and better perception of their
      health, as well as a more capacious and compliant rectum.

PMID- 22965407
TI  - The influence of health literacy on comprehension of a colonoscopy preparation
      information leaflet.
AB  - BACKGROUND: Successful bowel preparation is important for safe, efficacious, cost
      effective colonoscopy procedures; however, poor preparation is common. OBJECTIVE:
      We sought to determine whether there was an association between health literacy
      and comprehension of typical written instructions on how to prepare for a
      colonoscopy to enable more targeted interventions in this area. DESIGN: This is a
      cross-sectional observational study. SETTING: This study was performed at primary
      care clinics and federally qualified health centers in Chicago, Illinois.
      PATIENTS: Seven hundred sixty-four participants (mean age, 63 years; SD, 5.42)
      were recruited. The sample was from a mixed sociodemographic background, and
      71.9% of the participants were classified as having adequate health literacy
      scores. INTERVENTION: Seven hundred sixty-four participants were presented with
      an information leaflet outlining the bowel preparatory instructions for
      colonoscopy. MAIN OUTCOME MEASURES: Five questions were used to assess
      participants' comprehension of the instructions in an "open book" test. RESULTS:
      Comprehension scores on the bowel preparation items were low. The mean number of
      items correctly answered was 3.2 (SD, 1.2) of a possible 5. Comprehension scores
      overall and for each individual item differed significantly by health literacy
      level (all p < 0.001). After controlling for sex, age, race, socioeconomic
      status, and previous colonoscopy experience in a multivariable model, health
      literacy was a significant predictor of comprehension (inadequate vs adequate:
      beta = -0.2; p < 0.001; marginal vs adequate: beta = -0.2; p < 0.001).
      LIMITATIONS: The outcome represents a simulated task and not actual comprehension
      of preparation instructions for participants' own recommended behavior.
      CONCLUSIONS: Comprehension of a written colonoscopy preparation leaflet was
      generally low and significantly lower among people with low health literacy. Poor
      comprehension has implications for the safety and economic impact of
      gastroenterological procedures such as colonoscopy. Therefore, future
      interventions should aim to improve comprehension of complex medical information
      by reducing literacy-related barriers.

PMID- 22965408
TI  - Endoscopic and medical therapy for chronic radiation proctopathy:  a systematic
      review.
AB  - BACKGROUND: Chronic radiation proctopathy is associated with significant
      morbidity. The effectiveness of endoscopic and medical therapies has not been
      evaluated. OBJECTIVES: The aim of this study was to conduct a systematic review
      of the effectiveness of endoscopic and comparative medical therapies for chronic
      radiation proctopathy. DATA SOURCES: A comprehensive search Medline and PubMed
      was performed. STUDY SELECTION: A comprehensive literature search was performed
      for studies of endoscopic and medical therapy for clinical and endoscopic
      improvement in chronic radiation proctopathy from January 1990 until December
      2010. The quality of the overall evidence was rated according to the Grading of
      Recommendations, Assessment, Development, and Evaluation Working Group. SETTING:
      Patients in both inpatient and outpatient settings were assessed. PATIENTS:
      Patients experiencing chronic radiation proctopathy were included. INTERVENTIONS:
      Patients had undergone medical or endoscopic treatments for chronic radiation
      proctopathy. MAIN OUTCOME MEASUREMENTS: The primary outcomes measured were the
      resolution or improvement in symptoms. RESULTS: A total of 39 studies were found,
      of which 27 evaluated endoscopic therapy and 12 evaluated medical therapy chronic
      radiation proctopathy. Overall, there is low-level evidence for the effectiveness
      of endoscopic therapy with argon plasma coagulation in reducing short-term (<=6
      weeks) symptoms of chronic radiation proctopathy and insufficient evidence for
      long-term improvement. There is moderate-level evidence for the use of sucralfate
      enemas and low-level evidence for use of short-chain fatty acid enemas and
      hyperbaric oxygen. There is insufficient evidence for other agents: topical
      formalin, 5-aminosalicylic acid compounds, sulfasalazine, vitamin A, and
      pentoxifylline. LIMITATIONS: Individual authors were not contacted, and the
      search was limited to English language journals only. CONCLUSION: Endoscopic
      treatment with argon plasma coagulation appears effective in the short-term
      outcome of chronic radiation proctopathy. There is a moderate level of evidence
      for the use of sucralfate enemas. Large, randomized, placebo-controlled studies
      evaluating endoscopic and medical therapies for chronic radiation proctopathy are
      needed.

PMID- 22965410
TI  - Diversion with neoadjuvant vs surgery with adjuvant treatment for obstructing
      rectal cancer?

PMID- 22965411
TI  - Risk factors for anastomotic complications after resection for Crohn's disease.

PMID- 22965418
TI  - Genetic variation in the lactase gene, dairy product intake and risk for prostate
      cancer in the European prospective investigation into cancer and nutrition.
AB  - High dairy protein intake has been found to be associated with increased prostate
      cancer risk in the European Prospective Investigation into Cancer and Nutrition
      (EPIC). To further examine this possible relationship, we investigated the
      hypothesis that a genetic polymorphism in the lactase (LCT) gene might be
      associated with elevated dairy product intake and increased prostate cancer risk
      in a case-control study nested in EPIC. The C/T-13910 lactase variant (rs4988235)
      was genotyped in 630 men with prostate cancer and 873 matched control
      participants. Dairy product consumption was assessed by diet questionnaire. Odds
      ratios (ORs) for prostate cancer in relation to lactase genotype were estimated
      by conditional logistic regression. Lactase genotype frequency varied
      significantly between countries, with frequencies of the T (lactase persistence)
      allele ranging from 7% in Greece to 79% in Denmark. Intake of milk and total
      dairy products varied significantly by lactase genotype after adjustment for
      recruitment center; adjusted mean intakes of milk were 44.4, 69.8 and 82.3 g/day
      among men with CC, CT and TT genotypes, respectively. The lactase variant was not
      significantly associated with prostate cancer risk, both in our data (adjusted OR
      for TT vs. CC homozygotes: 1.10, 95% CI: 0.76-1.59) and in a meta-analysis of all
      the published data (combined OR for T allele carriers vs. CC homozygotes: 1.12,
      0.96-1.32). These findings show that while variation in the lactase gene is
      associated with milk intake in men, the lactase polymorphism does not have a
      large effect on prostate cancer risk.

PMID- 22965419
TI  - Overexpression of alternative oxidase gene confers aluminum tolerance by altering
      the respiratory capacity and the response to oxidative stress in tobacco cells.
AB  - Aluminum (Al) stress represses mitochondrial respiration and produces reactive
      oxygen species (ROS) in plants. Mitochondrial alternative oxidase (AOX) uncouples
      respiration from mitochondrial ATP production and may improve plant performance
      under Al stress by preventing excess accumulation of ROS. We tested respiratory
      changes and ROS production in isolated mitochondria and whole cell of tobacco
      (SL, ALT 301) under Al stress. Higher capacities of AOX pathways relative to
      cytochrome pathways were observed in both isolated mitochondria and whole cells
      of ALT301 under Al stress. AOX1 when studied showed higher AOX1 expression in ALT
      301 than SL cells under stress. In order to study the function of tobacco AOX
      gene under Al stress, we produced transformed tobacco cell lines by introducing
      NtAOX1 expressed under the control of the cauliflower mosaic virus (CaMV) 35 S
      promoter in sensitive (SL) Nicotiana tabacum L. cell lines. The enhancement of
      endogenous AOX1 expression and AOX protein with or without Al stress was in the
      order of transformed tobacco cell lines > ALT301 > wild type (SL). A decreased
      respiratory inhibition and reduced ROS production with a better growth capability
      were the significant features that characterized AOX1 transformed cell lines
      under Al stress. These results demonstrated that AOX plays a critical role in Al
      stress tolerance with an enhanced respiratory capacity, reducing mitochondrial
      oxidative stress burden and improving the growth capability in tobacco cells.

PMID- 22965420
TI  - First knockdown gene expression in bat (Hipposideros armiger) brain mediated by
      lentivirus.
AB  - Lentivirus-mediated RNA interference (RNAi) is a potent experimental tool for
      investigating gene functions in vitro and in vivo. It has advantages that
      transgenic technology lacks. However, in vivo applications are difficult to apply
      in the central nervous system of non-model organisms due to the lack of a
      standard brain atlas and genetic information. Here, we report the development of
      an in vivo gene delivery system used in bat brain tissue for the first time,
      based on lentivirus (LV) vectors expressing short hairpin RNA (shRNA) targeting
      Hipposideros armiger forkhead box P2 (FoxP2). In vitro transfection into HEK 293T
      cell with the vector bearing the cassettes encoding FoxP2 shRNA verified the
      knockdown efficiency. Pseudovirus particles were administered via stereotactic
      intracerebral microinjection into the anterior cingulate cortex of H. armiger.
      FoxP2 is of major interest because of its role in sensorimotor coordination and
      probably in echolocation. Subsequent in situ hybridization validated the in vivo
      silencing of the target gene. This report demonstrates that LV-mediated
      expression of RNAi could achieve effective gene silencing in bats, a non-model
      organism, and will assist in elucidating the functions of bat genes.

PMID- 22965421
TI  - Systems-level analysis of clinically different phenotypes of juvenile
      nasopharyngeal angiofibromas.
AB  - OBJECTIVES/HYPOTHESIS: To explore the molecular genetic background of juvenile
      nasopharyngeal angiofibromas and to identify biological processes and putative
      factors determining the different growth patterns of these tumors. STUDY DESIGN:
      By comparing copy number and gene expression level changes of two clinically
      different phenotypes of juvenile nasopharyngeal angiofibromas, we aimed to find
      processes essential in the growth and development of these tumors. Based on the
      results and prior knowledge of the proteins significance for growth, we studied
      the expression of tyrosine kinase SYK in 27 tumor samples. METHODS: Comparative
      genomic hybridization and gene expression analyses were performed for the two
      tumor samples, and protein expression of SYK was studied in 27 samples by
      immunohistochemical staining. RESULTS: Between low- and high-stage juvenile
      nasopharyngeal angiofibromas, 1,245 genes showed at least a two-fold change in
      expression. The corresponding proteins of these transcripts were enriched in
      different biological processes. Protein kinase SYK was expressed in all 27
      samples, and its intensity significantly correlated with tumor stage.
      CONCLUSIONS: Because the molecular genetic background of juvenile nasopharyngeal
      angiofibroma is unknown, our aim was to investigate genomic alterations that
      could associate to low- and high-stage tumors. We were able to identify gene
      expression changes that relate to particular biological processes, but assessing
      clinically relevant molecular profiles still requires further characterization.
      Due to the low incidence of juvenile angiofibroma, in the future a combination of
      molecular profiling data from several studies would be useful in understanding
      the molecular background of the disease.

PMID- 22965422
TI  - Diagnosis of type II enteropathy-associated T-cell lymphoma should be limited to
      EBER-cases.

PMID- 22965423
TI  - SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in the United
      States because most patients are diagnosed too late in the course of the disease
      to be treated effectively. Thus, there is a pressing need to more clearly
      understand how gene expression is regulated in cancer cells and to identify new
      biomarkers and therapeutic targets. Translational regulation is thought to occur
      primarily through non-SMAD directed signaling pathways. We tested the hypothesis
      that SMAD4-dependent signaling does play a role in the regulation of mRNA entry
      into polysomes and that novel candidate genes in pancreatic cancer could be
      identified using polysome RNA from the human pancreatic cancer cell line BxPC3
      with or without a functional SMAD4 gene. We found that (i) differentially
      expressed whole cell and cytoplasm RNA levels are both poor predictors of
      polysome RNA levels; (ii) for a majority of RNAs, differential RNA levels are
      regulated independently in the nucleus, cytoplasm, and polysomes; (iii) for most
      of the remaining polysome RNA, levels are regulated via a "tagging" of the RNAs
      in the nucleus for rapid entry into the polysomes; (iv) a SMAD4-dependent pathway
      appears to indeed play a role in regulating mRNA entry into polysomes; and (v) a
      gene list derived from differentially expressed polysome RNA in BxPC3 cells
      generated new candidate genes and cell pathways potentially related to pancreatic
      cancer.

PMID- 22965424
TI  - Downregulation of tropomyosin-1 in squamous cell carcinoma of esophagus, the role
      of Ras signaling and methylation.
AB  - Tropomyosins (TMs) are a family of cytoskeletal proteins that bind to and
      stabilize actin microfilaments. Non-muscle cells express multiple isoforms of TMs
      including three high molecular weight (HMW) isoforms: TM1, TM2, and TM3. While
      reports have indicated downregulation of TMs in transformed cells and several
      human cancers, nevertheless, little is known about the underlying mechanism of
      TMs suppression. In present study the expression of HMW TMs was investigated in
      squamous cell carcinoma of esophagus (SCCE), relative to primary cell cultures of
      normal esophagus by western blotting and real-time RT-PCR. Our results showed
      that TM1, TM2, and TM3 were significantly downregulated in cell line of SCCE.
      Moreover, mRNA level of TPM1 and TPM2 were markedly decreased by 93% and 96%, in
      tumor cell line relative to esophagus normal epithelial cells. Therefore,
      downregulation of TMs could play an important role in tumorigenesis of esophageal
      cancer. To asses the mechanism of TM downregulation in esophageal cancer, the
      role of Ras dependent signaling and promoter hypermethylation were investigated.
      We found that inhibition of two Ras effectory downstream pathways; MEK/ERK and
      PI3K/Akt leads to significant increased expression of TM1 protein and both TPM1
      and TPM2 mRNAs. In addition, methyltransferase inhibition significantly
      upregulated TM1, suggesting the prominent contribution of promoter
      hypermethylation in TM1 downregulation in esophageal cancer. These data indicate
      that downregulation of HMW TMs occurs basically in SCCE and the activation of
      MEK/ERK and PI3K/Akt pathways as well as the epigenetic mechanism of promoter
      hypermethylation play important role in TM1 suppression in SCCE.

PMID- 22965425
TI  - Gut microbiota: Adding weight to the microbiota's role in obesity--exposure to
      antibiotics early in life can lead to increased adiposity.

PMID- 22965427
TI  - Motility: Colonic manometry helps children who deny sensation to defecate.

PMID- 22965430
TI  - Refractory inflammatory bowel disease-could it be an irritable bowel?
AB  - Patients with IBD who are apparently in remission-as indicated by normal blood
      tests, endoscopic findings and ultrasonography results-often continue to
      experience symptoms. Furthermore, despite these negative findings, there is a
      temptation to increase their anti-inflammatory medication in the hope that this
      approach would lead to some improvement. However, this strategy often seems to
      fail and can sometimes lead to adverse events. Consequently, when evidence of
      continuing inflammatory activity is lacking it might be appropriate to consider
      the possibility of co-existent IBS in these patients and to treat them for this
      condition. Dietary manipulation, antispasmodic agents, antidepressants
      (especially of the tricyclic variety) and even behavioural treatments might
      result in a worthwhile improvement of symptoms.

PMID- 22965426
TI  - Regulation of gastrointestinal motility--insights from smooth muscle biology.
AB  - Gastrointestinal motility results from coordinated contractions of the tunica
      muscularis, the muscular layers of the alimentary canal. Throughout most of the
      gastrointestinal tract, smooth muscles are organized into two layers of
      circularly or longitudinally oriented muscle bundles. Smooth muscle cells form
      electrical and mechanical junctions between cells that facilitate coordination of
      contractions. Excitation-contraction coupling occurs by Ca(2+) entry via ion
      channels in the plasma membrane, leading to a rise in intracellular Ca(2+).
      Ca(2+) binding to calmodulin activates myosin light chain kinase; subsequent
      phosphorylation of myosin initiates cross-bridge cycling. Myosin phosphatase
      dephosphorylates myosin to relax muscles, and a process known as Ca(2+)
      sensitization regulates the activity of the phosphatase. Gastrointestinal smooth
      muscles are 'autonomous' and generate spontaneous electrical activity (slow
      waves) that does not depend upon input from nerves. Intrinsic pacemaker activity
      comes from interstitial cells of Cajal, which are electrically coupled to smooth
      muscle cells. Patterns of contractile activity in gastrointestinal muscles are
      determined by inputs from enteric motor neurons that innervate smooth muscle
      cells and interstitial cells. Here we provide an overview of the cells and
      mechanisms that generate smooth muscle contractile behaviour and gastrointestinal
      motility.

PMID- 22965432
TI  - Hepatocellular carcinoma--resection or transplant?
AB  - Resection and liver transplantation are considered effective treatments for early
      stage hepatocellular carcinoma (HCC). As data from randomized trials are lacking,
      the choice of technique is controversial. Retrospective analyses suggest that for
      patients with suboptimal liver function, transplantation is the preferred
      treatment. For patients with preserved liver function and HCC within the Milan
      criteria, the overall survival rate is similar for both techniques; therefore
      resection is the preferred treatment. For tumours beyond the Milan criteria but
      within acceptable expanded criteria, transplantation has a more favourable
      outcome than resection. As liver grafts are in short supply, resection followed
      by transplantation once intrahepatic recurrence is detected would spare patients
      with favourable or very aggressive tumours from transplantation and enable
      patients with moderately aggressive tumours to undergo timely transplantation.
      Currently, resection and transplantation are considered complementary in the
      management of HCC. Expanding the transplantation and resection criteria of HCC
      needs to be investigated.

PMID- 22965434
TI  - Prognosis and quality of life of elderly patients after intensive care.
AB  - Ageing of the world's population raises important questions about the utilisation
      of the health care system. It is not clear how much should be invested in the
      last years of life whereas the costs are known to increase in parallel. Since
      intensive care units (ICU) are costly with highly specialised personnel, it seems
      of paramount importance that they would be used efficiently. Indeed, in the
      present context of predicted shortage of physicians in Switzerland, society and
      politics will need evidence that the care provided by ICUs is appropriate. There
      is no explicit limitation of care in any country according to age and nonagerians
      are admitted nowadays into ICUs with critical illness. This review article will
      address the question of elderly patients in ICU and their outcome. Outcome does
      not imply surviving ICU but only later during the hospital stay and after
      discharge. Furthermore, we emphasise the need of examining not solely the
      hospital survival but the quality of life of the patients when they return to
      their real life. The fundamental questions are actually "Do they go back to
      life?" "What is life for elderly people?" These questions lead to more basic
      questions such as "Are they able to go back home or are they institutionalised?
      How is their quality of life and functional status after ICU?". We tried to
      address these questions through the existing literature and our experience while
      caring for these particular patients. Some clues on the prognostic factors
      related to their outcome are reported.

PMID- 22965437
TI  - TheMedical Insurance for a New Generation: another step towards universal health
      coverage in Mexico.

PMID- 22965435
TI  - Role of circulating MSCs in vocal fold wound healing.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold injury can cause intractable scarring resulting
      in dysphonia. Mesenchymal stem cells (MSCs) have great therapeutic potential in
      wound healing. They continuously circulate in the peripheral blood and migrate
      into wound sites where they induce regenerative effects. However, their roles in
      vocal fold wound healing are poorly understood because few MSCs exist in the
      peripheral blood and there is no specific marker to identify them. The present
      study evaluates how intravenously injected MSCs affect vocal fold wound healing
      using Green Fluorescent Protein (GFP) -labeled MSCs. STUDY DESIGN: Prospective
      study using animal model. METHODS: GFP-labeled MSCs were obtained from femurs of
      GFP transgenic Sprague-Dawley rats and incubated in culture. Sprague-Dawley rats
      underwent intravenous injection of GFP-labeled MSCs (1.0 * 10(6) cells)
      immediately after vocal fold injury. Histological examination was performed.
      RESULTS: Injected MSCs were distributed throughout the vocal fold wound site from
      day 1 up to day 56. These vocal folds showed increased hepatocyte growth factor
      (HGF)-positive cells within the wound and improved wound healing compared with
      sham-treated folds. CONCLUSION: Circulating MSCs can migrate to vocal fold wound
      sites and upregulate the expression of HGF during wound healing; thus, they are
      considered to play a significant role in wound healing within the vocal folds.

PMID- 22965438
TI  - Design of the 2009 evaluation of the Medical Insurance for a New Generation
      program.
AB  - OBJECTIVE: To describe the mixed-method approach to evaluate the Medical
      Insurance for a New Generation (Seguro Medico para una Nueva Generacion, SMNG).
      MATERIALS AND METHODS: The program has been comprehensively evaluated. It has
      four key domains: 1) SMNG design; 2) children's health status and socio
      demographic characteristics; 3) performance by measuring coverage, efficiency and
      productivity; 4) family health expenditure. Quantitative and qualitative research
      approaches have been used. This included reviews of existing databases and
      clinical charts, collection of empirical data through in-depth interviews with
      healthcare providers, and a nation-wide household survey. CONCLUSION: The results
      should serve as baseline data of the health status of SMNG children and the
      current staus of the program.

PMID- 22965439
TI  - Feeding practices and nutritional status of Mexican children affiliated to the
      Medical Insurance for a New Generation.
AB  - OBJECTIVE: To identify feeding practices and nutritional status in children
      affiliated to the Medical Insurance for a New Generation (SMNG). MATERIALS AND
      METHODS: An in-home survey addressed to mothers which included anthropometric
      measures of children; performed in March and April 2009 in Mexican States.
      RESULTS: The prevalence of any form of breastfeeding was (months) 6-11: 67.9%; 12
      17: 43.6%; 18-23: 26.4%; >23: 16.7%; with higher figures in rural children. BF
      duration was eight months. Continued breastfeeding at 1 year of age was 43%. At 1
      year of age, almost all children consumed fruits, vegetables, cereals and
      legumes; however, 13.5%-20.3% did not consume foods of animal origin, but ~84%
      and ~60% consumed fried and sweet foods and soft drinks. Nutrisano (a food
      supplement) was consumed by just 2/3 of the Oportunidades Children. Stunting and
      overweight were the predominant alterations of nutritional status. CONCLUSION:
      Improving the nutritional status of children affiliated to the SMNG requires
      promotion of appropriate healthy dietary practices and the surveillance of infant
      growth.

PMID- 22965440
TI  - Utilization of healthcare services among children members of Medical Insurance
      for a New Generation.
AB  - OBJECTIVE: To describe the utilization and associated factors for preventive and
      curative care utilization among children affiliated to the Medical Insurance for
      a New Generation (SMNG). MATERIALS AND METHODS: Data from the 2009 National
      Survey of SMNG was analyzed. RESULTS: The analysis represented 1,316,867
      children; 25% of urban and 37.5% of rural mothers that took their children to
      well-child visits. Covariates associated with preventive care utilization were
      children <12 months, low-birth weight, history of infectious or other diseases,
      mother >35 years, mother's literacy level of bachelor degree, housewife,
      attendance at >7 antenatal care visits, and living in a rural area. Curative
      care: 12% attended emergency room services, 5.4% were hospitalized and 66%
      received ambulatory care. Covariates associated with curative care utilization:
      child history of frequent diseases, mother living with husband/partner, mother's
      literacy level of bachelor degree, attendance >7 antenatal care visits and having
      paid work. CONCLUSION: It is needed to reinforce the programs encouraging mothers
      to seek preventive care regularly.

PMID- 22965441
TI  - The Medical Insurance for a New Generation: a viable answer for the health needs
      of Mexican children.
AB  - OBJECTIVE: To describe the Medical Insurance for a New Generation (SMNG) as key
      public policy aimed at improving health care services for children under the age
      of five years in Mexico. MATERIALS AND METHODS: This paper analyzes interrelated
      aspects of public policies to provide health care to Mexican children: a) the
      demographic and health status of children, with emphasis on the wide disparities
      between children of varying demographics; b) the relationship of the main
      functions of a health care system: financing, equity, access and quality, with
      the provision of health care for children; c) the architecture of the Medical
      Insurance for a New Generation. CONCLUSION: SMNG is a program that can be
      instrumental in lowering infant mortality and alleviating the burden of families
      to care for sick children by improving access, quality of care and equity.

PMID- 22965442
TI  - Quality of health care of the medical units that provide services for Medical
      Insurance for a New Generation enrollees.
AB  - OBJECTIVE: In this evaluation we assess the quality of the general and clinical
      structure in medical units that deliver health services for the Medical Insurance
      for a New Generation (SMNG) enrollees. MATERIALS AND METHODS: The study
      population included 82 medical units that deliver health services to enrollees of
      the SMNG in 15 states of Mexico, during 2009. Two indexes: the general structure
      index and the clinical structure index were created. RESULTS: It was found an
      unequal quality of the general and clinical structure in the different levels of
      care. The results suggest that the first level of care lacks both important
      general and clinical structural items. They also show on average a regular
      quality in the second level of care and a good quality in the third level of care
      medical units. CONCLUSIONS: Our results support the main conclusion of the work
      of Bulatao, "Improving services requires moving beyond policy reform to
      strengthening implementation of services".

PMID- 22965443
TI  - The use of the tracer methodology to assess the quality of care for patients
      enrolled in Medical Insurance for a New Generation.
AB  - OBJECTIVE: To assess the quality of care provided at medical units that provide
      services to Medical Insurance for a New Generation (SMNG) enrollees. MATERIALS
      AND METHODS: The tracer methodology was used in a sample of 82 medical units
      selected in fifteen states of Mexico and data collected in November 2009.
      RESULTS: Problems were found to locate the minimal number of the 18 medical
      charts requested in three of the tracers. The first level of care on the average
      reports that the quality of the process of care is 6, in a 10 point scale. In the
      second level improves and the third level of care is better qualified.
      CONCLUSIONS: The tracer methodology has enabled us to assess the quality of care.
      There is room for improvement in the medical units of the state health services,
      to that end should be directed the efforts in the health system in Mexico.

PMID- 22965444
TI  - Recommendations to improve healthcare of neonates with respiratory insufficiency
      beneficiaries of Seguro Popular.
AB  - OBJECTIVE: To evaluate the structure and processes of care of neonatal intensive
      care units (NICU) providing health care to neonates with respiratory
      insufficiency, and financed by Seguro Popular. MATERIALS AND METHODS: A cross
      sectional design was used; 21 NICU were included. Information was collected from
      four sources: Seguro Popular database, self-applicable interviews to medical
      staff, structure and processes format, and reviews of clinical charts. VARIABLES:
      structure, processes of care, drug supplies, training, and neonates' clinical
      conditions. RESULTS: The analysis of the database included 9 679 newborns. The
      respiratory disorders were transitory tachypnea, non-specific respiratory
      insufficiency, respiratory distress syndrome, (RDS) perinatal asphyxia, and
      meconium aspiration syndrome. 90% of NICU'S directors considered that drug supply
      was good, whereas only 16% of neonatologist had this opinion. 58.5% of neonates
      with RDS had <37 gestation weeks. 34.2% with RDS were prescribed alveolar
      surfactant; 51% received dosages above recommended standards. CONCLUSIONS:
      Recommendations to improve infrastructure and care processes are issued.

PMID- 22965445
TI  - Family healthcare expenditure on children affiliated to the Medical Insurance for
      a New Generation.
AB  - OBJECTIVE: To analyze household health expenditures on children who are
      beneficiaries of the Medical Insurance for a New Generation (SMNG), program
      created in 2007 to cover healthcare costs of children without social security
      born after December 1st, 2006. MATERIALS AND METHODS: Using the SMNG National
      Survey, out-the-pocket and catastrophic spending on child health were calculated
      using several definitions. Results are presented by socioeconomic level, rural
      and urban areas and for Oportunidades beneficiaries. RESULTS: About 63.3% of
      households spent an average annual amount of 3320 Mexican pesos (MEX$) on
      healthcare for beneficiary children. Between 4.3 and 11.6% of households
      experienced catastrophic spending, depending on the definition adopted. Due to
      economic trouble, 15.5% of households postponed and 10.0% cancelled medical care
      for their child. CONCLUSIONS: Even though children are affiliated to the SMNG,
      the economic burden associated with attending their health is still an issue for
      families.

PMID- 22965446
TI  - Economic evaluation of the use of exogenous pulmonary surfactants in preterm
      newborns in a Mexican population.
AB  - OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue
      treatment of premature infants with respiratory distress syndrome (RDS) who are
      covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A
      cost-effectiveness evaluation was conducted from the third-payer perspective.
      Comparisons were made between the use of bovine surfactant (BS) therapy and
      without BS therapy. A decision tree model with a lifetime horizon was used where
      the measurements of effectiveness were life years gained (LYG) and quality
      adjusted life years (QALYs). A 5% discount rate was considered for costs and
      health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS:
      Incremental cost-effectiveness ratios (ICER) were MXN$136,670 per LYG and
      MXN$125,250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost
      effective strategy in accordance with World Health Organization criteria of three
      per capita gross domestic product (GDP) per QALY in premature infants with RDS in
      Mexico.

PMID- 22965447
TI  - Physical growth and nutritional status of Mexican infants from newborn to two
      years of age.
AB  - OBJECTIVE: To determine the nutritional status of Mexican infants under two years
      of age. MATERIALS AND METHODS: Five nutritional surveys, three being
      representative of the nation, were assessed using several anthropometric
      indicators, with reference to the WHO 2006 growth standard. RESULTS: From
      national surveys, the incidence of low birth weight ranged from 8.9 to 8.1% and
      was higher in rural areas. At two years of age, the prevalences of stunted
      growth, wasting and being overweight ranged from 25.6 to 16.1%, 4.5 to 1.9% and
      6.3 to 10.8%, respectively, between 1988 and 2006. The combination of being
      overweight with stunted growth increased with age, particularly in rural areas.
      Figures presented in non-national surveys compared with national surveys
      demonstrate a lower incidence of low birth weight, similar levels of stunted
      growth, being overweight and obesity, and a little higher for wasting.
      CONCLUSION: Policies are required to be implemented to prevent nutritional
      diseases associated with stunted growth, being overweight and obesity.

PMID- 22965448
TI  - Lessons learned from the first evaluation of the Medical Insurance for a New
      Generation: bridging research and policy.
AB  - The first evaluation of the Medical Insurance for a New Generation program (SMNG)
      was conducted in 2009. A mixed-method approach was used to obtain a comprehensive
      picture of SMNG members and the program itself. The evaluation comprised: 1)
      Program design; 2) Social and health conditions of its members; 3); Evaluation of
      SMNG's performance by measuring coverage, productivity and efficiency; 4)
      Families health expenditures. The lessons learned for the program are that SMNG
      is focused on a vulnerable segment of the population with pervasive unmet health
      needs; prevalence of malnutrition, anemia and other conditions remains high.
      Further efforts are necessary to deploy the program where it is most needed,
      particularly in rural areas; most of its members are urban dwellers. However,
      more needs to be done to educate members about the importance of preventive care
      and to build the capability of health providers to provide high quality care.
      Families are still experiencing hardship to provide medical care to their
      children, so additional efforts are needed to decrease out-of-pocket and
      catastrophic expenditures. The lessons learned for the evaluation allow
      concluding that this first evaluation set the groundwork for better-targeted
      subsequent interventions and evaluations aimed at showing the impact of SMNG to
      bridge existing gaps in equity, access, coverage, and health status of Mexican
      children.

PMID- 22965449
TI  - Sociodemographic characteristics of SMNG affiliates.

PMID- 22965451
TI  - An efficient broadband and omnidirectional light-harvesting scheme employing a
      hierarchical structure based on a ZnO nanorod/Si3N4-coated Si microgroove on 5
      inch single crystalline Si solar cells.
AB  - We employ a ZnO nanorod/Si(3)N(4)-coated Si microgroove-based hierarchical
      structure (HS) for a light-harvesting scheme in 5 inch single crystalline Si
      solar cells. ZnO nanorods and Si microgrooves were fabricated by a simple and
      scalable aqueous process. The excellent light-harvesting characteristics of the
      HS, such as broadband working ranges and omnidirectionality have been
      demonstrated using external quantum efficiencies and reflectance measurements.
      The solar cells with the hierarchical surface exhibit excellent photovoltaic
      characteristics, i.e., a short-circuit current (J(SC)) of 38.45 mA cm(-2), open
      circuit voltage of 609 mV and conversion efficiency of 14.04%. As incident angles
      increase from 0 degrees  to 60 degrees , only 5.3% J(SC) loss is achieved by
      employing the hierarchical surface, demonstrating the enhanced omnidirectional
      photovoltaic performances, also confirmed by the theoretical analysis. A viable
      scheme for broadband and omnidirectional light harvesting using the HS employing
      microscale/nanoscale surface textures on single crystalline Si solar cells has
      been demonstrated.

PMID- 22965450
TI  - Phylogenetic analysis of porcine astrovirus in domestic pigs and wild boars in
      South Korea.
AB  - Porcine astrovirus (PAstV) belongs to genetically divergent lineages within the
      genus Mamastrovirus. In this study, 25/129 (19.4 %) domestic pig and 1/146 (0.7
      %) wild boar fecal samples tested in South Korea were positive for PAstV.
      Positive samples were mainly from pigs under 6 weeks old. Bayesian inference (BI)
      tree analysis for RNA-dependent RNA polymerase (RdRp) and capsid (ORF2) gene
      sequences, including Mamastrovirus and Avastrovirus, revealed a relatively
      geographically divergent lineage. The PAstVs of Hungary and America belong to
      lineage PAstV 4; those of Japan belong to PAstV 1; and those of Canada belong to
      PAstV 1, 2, 3, and 5, but not to 4. This study revealed that the PAstVs of Korea
      belong predominantly to lineage PAstV 4 and secondarily to PAstV 2. It was also
      observed that PAstV infections are widespread in South Korea regardless of the
      disease state in domestic pigs and in wild boars as well.

PMID- 22965453
TI  - Processing of degradable ulvan 3D porous structures for biomedical applications.
AB  - The interest in ulvan within a biomedical framework increases as the knowledge of
      this polysaccharide evolves. Ulvan has been recently proposed as a potential
      biomaterial, and structures based on this polysaccharide are now being studied
      for different biomedical applications. In this work, a novel porous structure
      based on cross-linked ulvan was designed and characterized. Its mechanical
      performance, water-uptake ability and weight loss were assessed, morphology
      analyzed through scanning electron microscopy, and morphometric parameters
      quantified by microcomputed tomography. Cell viability and cell proliferation
      were evaluated in order to estimate the cytotoxicity of these structures and
      respective degradation products. Produced ulvan structures revealed remarkable
      ability to uptake water (up to ~ 2000% of its initial dry weight) and are
      characterized by a highly porous and interconnected structure. Furthermore, these
      ulvan structures underwent nontoxic degradation, and cells remained viable
      through the time of culture. These results position ulvan structures as
      prospective blocks that can be further functionalized in order to acquire the
      desired stability and needed biological interactivity to be used as tissue
      engineered structures. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A, 2013.

PMID- 22965454
TI  - New synthesis: chemical ecology and sustainable food production.

PMID- 22965452
TI  - Estradiol-induced increase in novel object recognition requires hippocampal NR2B
      containing NMDA receptors.
AB  - 17beta-estradiol (E2), at high circulating levels, enhances learning and memory
      in many women, making it a clinical treatment for hormone-related cognitive
      decline in aging. However, the mechanisms stimulated by E2, which are responsible
      for its cognitive enhancing effects, remain incompletely defined. Using an
      ovariectomized rat model, we previously reported that increasing plasma E2
      enhances the magnitude of long-term potentiation (LTP) at hippocampal CA3-CA1
      synapses, which is caused by a selective increase in current mediated by NR2B
      containing NMDARs, leading to an increase in the NMDAR/AMPAR ratio. Whether the
      increase in NR2B current is causally related to the ability of E2 to enhance
      hippocampal dependent learning and memory has yet to be tested. Here, we find
      that E2 enhances performance in the novel object recognition (NOR) task with the
      same time course we previously showed E2 enhances the LTP magnitude, temporally
      linking the increase in LTP to enhanced learning and memory. Furthermore, using
      the selective NR2B subunit antagonist Ro25-6981, we find that the E2-enhanced
      NOR, like the enhanced LTP, requires hippocampal NR2B-containing NMDARs,
      specifically in area CA1. Finally, using whole-cell recordings and the
      phosphatase inhibitor orthovanadate, we investigated whether the E2-induced
      increase in NMDAR current is caused by an increase in the density of synaptic
      NMDARs and/or an increase in NMDAR subunit phosphorylation. We find that both
      mechanisms are responsible for the enhanced NMDAR current in E2-treated rats. Our
      results show that the E2-enhanced NOR requires a functional increase in NR2B
      containing NMDARs, a requirement shared with the E2-enhanced LTP magnitude at CA3
      CA1 synapses, supporting the hypothesis that the increase in LTP likely
      contributes to the enhanced learning and memory following an increase in plasma
      E2 levels.

PMID- 22965455
TI  - Intermolecular oxidative annulation of 2-aminoanthracenes to diazaacenes and
      aza[7]helicenes.

PMID- 22965456
TI  - beta-elemene induces glioma cell apoptosis by downregulating survivin and its
      interaction with hepatitis B X-interacting protein.
AB  - beta-elemene, extracted from the ginger plant, possesses antitumor activity
      against a broad range of cancers clinically. However, the mechanism underlying
      beta-elemene-induced cytotoxicity remains incompletely understood. Here, we show
      that beta-elemene promoted apoptotic cell death in human glioma cells,
      downregulated survivin gene expression, and induced caspase-9, -3 and -7
      activities. Induction of apoptosis was associated with inhibition of survivin
      gene expression, and restoration of survivin levels remarkably attenuated beta
      elemene-induced glioma cell death. Moreover, we found that the interaction
      between surviving and HBXIP, a critical regulator of caspase-9 activity, was
      impaired by beta-elemene treatment. The results, therefore, reveal a caspase
      mediated apoptotic pathway induced by beta-elemene in human glioma cells, which
      is associated with downregulation of survivin itself and the interaction between
      survivin and HBXP.

PMID- 22965457
TI  - Cardioprotective effect of sevoflurane and propofol during anaesthesia and the
      postoperative period in coronary bypass graft surgery:  a double-blind randomised
      study.
AB  - CONTEXT: Volatile anaesthetics may have direct cardioprotective properties due to
      effects similar to ischaemic preconditioning and postconditioning. Clinical
      results in cardiac surgery patients are controversial and may be related to the
      timing of administration of anaesthetics intraoperatively. OBJECTIVE: We
      hypothesised that the cardioprotective effect of sevoflurane in coronary bypass
      graft surgical patients would be greater if administration during anaesthesia
      continued in the ICU for at least 4 h postoperatively until weaning from
      mechanical ventilation. DESIGN: Double-blind, double-dummy, prospective,
      randomised and controlled clinical trial. SETTING: In a single centre between
      June 2006 and June 2007. PATIENTS: Seventy-five adult patients were assigned
      randomly to receive anaesthesia and postoperative sedation either with propofol
      (control, n = 37) or sevoflurane (n = 36). INTERVENTIONS: Myocardial biomarkers
      were measured before surgery, at the time of admission to the intensive care unit
      and at 6, 24, 48 and 72 h. The need for inotropic support, and lengths of stay in
      the intensive care unit and hospital were also recorded. MAIN OUTCOME MEASURES:
      Elevation of myocardial biomarkers was the primary endpoint. The secondary
      endpoints were haemodynamic events and lengths of stay in the intensive care unit
      and hospital. RESULTS: Necrosis biomarkers increased significantly in the
      postoperative period in both groups with no significant differences at any time.
      Inotropic support was needed in 72.7 and 54.3% of patients in the propofol and
      sevoflurane groups, respectively (P = 0.086). There were no significant
      differences in haemodynamic variables, incidence of arrhythmias, myocardial
      ischaemia or and lengths of stay in the ICU and hospital between the two groups.
      CONCLUSION: In patients undergoing coronary bypass graft surgery, continuous
      administration of sevoflurane as a sedative in the ICU for at least 4 h
      postoperatively did not yield significant improvements in the extent and time
      course of myocardial damage biomarkers compared to propofol.

PMID- 22965458
TI  - A randomised comparison of the effects of low-dose spinal or general anaesthesia
      on umbilical cord blood gases during caesarean delivery of growth-restricted
      foetuses with impaired Doppler flow.
AB  - CONTEXT: Hypotension following spinal anaesthesia for caesarean delivery may
      decrease uteroplacental perfusion and produce foetal acidosis. The optimal
      anaesthetic technique for mothers with foetal growth restriction and impaired
      Doppler flow is unclear. OBJECTIVE: To compare the effects of low-dose spinal
      anaesthesia and general anaesthesia on neonatal outcome and maternal
      haemodynamics. DESIGN: Prospective, randomised clinical trial. SETTING: Tertiary
      care hospital. PATIENTS: Forty pregnant women with foetal growth restriction and
      impaired Doppler flow scheduled for elective caesarean delivery. INTERVENTIONS:
      The women were allocated randomly to receive a low-dose spinal anaesthetic (8-mg
      hyperbaric bupivacaine 0.5% with fentanyl 20 MUg) or standard general anaesthesia
      for elective caesarean delivery. SBP was maintained between 80 and 100% of
      baseline using bolus doses of phenylephrine. The total duration of hypotension,
      dose of phenylephrine used and any incidence of hypotension, nausea or vomiting
      were recorded. MAIN OUTCOME MEASURES: The primary outcome variable was arterial
      and venous umbilical cord base deficit. Neonatal outcome and maternal
      haemodynamics were analysed as secondary endpoints. RESULTS: The mean umbilical
      artery pH was significantly lower in the low-dose spinal anaesthesia group than
      in the general anaesthesia group (7.23 +/- 0.06 vs. 7.27 +/- 0.04, P = 0.01).
      Cord base deficit was similar in the two groups. Higher partial pressures of
      oxygen occurred in the general anaesthesia group (20.9 +/- 6.5 kPa) than in the
      low-dose spinal anaesthesia group (13.6 +/- 6.1 kPa, P = 0.001). No difference
      was observed between groups in 1 and 5-min Apgar scores. There appeared to be a
      greater need for immediate resuscitation of neonates in the general anaesthesia
      group, but the difference was not statistically significant (P = 0.51). Low-dose
      spinal anaesthesia was associated with hypotension of short duration (0.7 +/- 1.1
      min). CONCLUSION: In this study, there was no difference in umbilical cord base
      deficit between the groups. Larger studies would be required to assess whether
      the mode of anaesthesia influences the incidence of clinically important neonatal
      acidosis in neonates with foetal growth restriction.

PMID- 22965460
TI  - Etomidate for critically ill patients. Con:  do you really want to weaken the
      frail?
AB  - Etomidate is an imidazole-derived hypnotic agent preferentially used for rapid
      sequence induction of anaesthesia because of its favourable haemodynamic profile.
      However, 11beta-hydroxylase inhibition causes adrenal insufficiency with
      potentially fatal consequences in specific populations. We review the arguments
      against the liberal administration of etomidate in critically ill, and especially
      septic, patients. This review considered only high-quality and prospective
      studies with a low risk of bias. Three major effects have been observed with the
      clinical use of a single dose of etomidate. First, independent of the clinical
      setting, etomidate causes adrenal dysfunction via 11beta-hydroxylase inhibition
      ranging from 12 to 48 h, making the drug unsuitable for use in elective
      interventions. Second, in a systematic review with meta-analyses, including 3715
      septic patients, the relative risk of death with etomidate was 1.22 (95%
      confidence interval 1.11 to 1.35). Based on this statistically significant and
      clinically relevant increase in mortality, a single dose of etomidate has to be
      avoided in patients with septic shock. Third, in small randomised controlled
      trials, a single dose of etomidate in trauma patients was associated with an
      increased incidence of pneumonia (56.7 vs. 25.9% in controls), prolonged
      intensive care stay (6.3 vs. 1.5 days) and prolonged hospital stay (11.6 vs. 6.4
      days). Based on these randomised controlled trials, the use of etomidate should
      be avoided in unstable trauma patients. Midazolam and ketamine are two valid
      alternatives with similar intubation and haemodynamic conditions as etomidate but
      without its adverse effects. Therefore, for safety reasons, etomidate should be
      avoided in the critical conditions of sepsis and trauma.

PMID- 22965459
TI  - Low-dose dexmedetomidine facilitates the carotid body response to low oxygen
      tension in vitro via alpha2-adrenergic receptor activation in rabbits.
AB  - CONTEXT: Some anaesthetics exert an inhibitory effect on the response of the
      carotid body to low oxygen tension. However, the effect of dexmedetomidine on the
      carotid body response has not been reported. OBJECTIVE: To investigate the effect
      of dexmedetomidine on carotid body activity. The hypothesis is that
      dexmedetomidine does not have an inhibitory effect on the response of the carotid
      body to low oxygen tension. DESIGN: Animal experimental study in vitro. Ten
      carotid bodies surgically removed from male New Zealand white rabbits were
      tested. SETTING: Research laboratory of Nippon Medical School, Tokyo, Japan, from
      July 2008 to February 2010. INTERVENTION: The carotid body was perfused with
      three different concentrations of dexmedetomidine (0.1, 1.0 and 10 nmol l). The
      contribution of alpha2-adrenergic receptors was evaluated by addition of 1.0 nmol
      l yohimbine, an alpha2-adrenergic receptor antagonist. MAIN OUTCOME MEASURES: The
      differences in carotid sinus nerve activity between high oxygen tension
      (baseline) and low oxygen tension (peak) were analysed. RESULTS: At all three
      concentrations, dexmedetomidine did not depress the baseline and peak activity of
      the carotid body, whereas 0.1 nmol l dexmedetomidine facilitated the response to
      low oxygen tension stimulation. The differences in carotid sinus nerve activity
      between baseline (pO2 80.4 +/- 9.1 kPa) and peak (pO2 22.1 +/- 2.6 kPa) were 140
      +/- 70 Hz in controls and 266 +/- 116 Hz with 0.1 nM dexmedetomidine (P < 0.05).
      This increase was not shown in the presence of 1.0 nmol l yohimbine. CONCLUSION:
      Dexmedetomidine does not depress the activity of the carotid body under high
      oxygen tension or the response to low oxygen tension, whereas 0.1 nmol l
      dexmedetomidine facilitates this response via alpha2-adrenergic receptor
      activation.

PMID- 22965461
TI  - Does mesenchymal stem cell population in umbilical cord blood vary at different
      gestational periods?
AB  - OBJECTIVE: To identify and quantitatively determine Mesenchymal stem cells (MSCs)
      in the umbilical cord blood (UCB) of neonates born at different gestational
      periods. METHODS: UCB was collected at birth in neonates of three different
      gestational groups. The mononuclear cells (MNCs) were phenotypically analyzed by
      flow cytometer. RESULTS: The yield of total MNCs did not differ much with
      gestation; the average values were 22.6 +/- 6.48 * 106 cells/ml. The MSCs were
      significantly higher in the lower gestation group. These were 0.0219 +/- 0.012 %,
      0.0044 +/- 0.003 % and 0.0022 +/- 0.003 % in 28 to 31 wk, 32 to 35 wk and >36 wk,
      respectively (P = 0.00). There was a significant inverse correlation between the
      gestational age and the presence of MSCs with a correlation co-efficient of -0.54
      (P = 0.0001). CONCLUSIONS: The MSCs population was significantly higher in
      infants born at lesser gestation than those born at term gestation.

PMID- 22965463
TI  - Prevention of gentamicin-induced apoptosis with the mitochondria-targeted
      antioxidant mitoquinone.
AB  - OBJECTIVES/HYPOTHESIS: Antioxidants have been shown to protect against
      aminoglycoside-induced hearing loss. Mitoquinone (MitoQ) is a mitochondria
      targeted derivative of the antioxidant ubiquinone. MitoQ is attached to a
      lipophilic triphenylphosphonium (TPP) cation, which enables its accumulation
      inside the mitochondria several hundred-fold over the untargeted antioxidant. The
      goals of this study were to determine if MitoQ attenuates gentamicin-induced
      activation of caspase-3/7 activity as a marker of apoptosis and to determine if
      MitoQ impacts aminoglycoside antimicrobial efficacy. STUDY DESIGN: Prospective
      and controlled. METHODS: Antibiotic efficacy and minimum inhibitory
      concentrations (MICs) of gentamicin against three strains each of Staphylococcus
      aureus, Haemophilus influenzae, and Pseudomonas aeruginosa were evaluated with
      and without MitoQ using broth dilution methods. Apoptosis was assessed by caspase
      3/7 activity in untreated HEI-OC1 cells and cells exposed to 2 mM gentamicin for
      24 hours, with and without a 24-hour preincubation with 0.5 MUM each of MitoQ,
      idebenone (an untargeted ubiquinone), or decylTPP (positive control). RESULTS:
      Gentamicin MICs for P aeruginosa and H influenzae were not affected by MitoQ at
      pharmacological levels. MICs for S aureus were enhanced by MitoQ. Cell viability
      was significantly lower in the gentamicin-treated cells. A significant increase
      in caspase-3/7 activity was observed in cells treated with gentamicin or with
      idebenone + gentamicin (P = .005). Preincubation with MitoQ decreased the
      gentamicin-induced apoptosis of HEI-OC1 cells to a greater extent compared to
      idebenone (P = .002). CONCLUSIONS: MitoQ attenuates gentamicin-induced apoptosis
      in HEI-OC1 cells and does not compromise gentamicin antibiotic efficacy. MitoQ
      holds promise as a means of preventing aminoglycoside ototoxicity.

PMID- 22965462
TI  - Optical molecular imaging detects changes in extracellular pH with the
      development of head and neck cancer.
AB  - Noninvasive localized measurement of extracellular pH in cancer tissues can have
      a significant impact on the management of cancer. Despite its significance, there
      are limited approaches for rapid and noninvasive measurement of local pH in a
      clinical environment. In this study, we demonstrate the potential of noninvasive
      topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated
      with Alexa Fluor((r))  647) to image changes in extracellular pH associated with
      head and neck squamous cell carcinoma using widefield and high resolution
      imaging. We report a series of preclinical analyses to evaluate the optical
      contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact
      fresh human tissue specimens using widefield and high-resolution fluorescence
      imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered
      throughout the epithelium of intact tissues with a depth exceeding 700 um.
      Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast
      increased four to eight fold higher in clinically abnormal tissues as compared to
      paired clinically normal biopsies. Furthermore, the imaging approach showed
      significant differences in fluorescence contrast between the cancer and the
      normal biopsies across diverse patients and different anatomical sites (unpaired
      comparison). The fluorescence contrast differences between clinically abnormal
      and normal tissues were in agreement with the pathologic evaluation. Topical
      application of fluorescently labeled pHLIP can detect and differentiate normal
      from cancerous tissues using both widefield and high resolution imaging. This
      technology will provide an effective tool to assess tumor margins during surgery
      and improve detection and prognosis of head and neck cancer.

PMID- 22965464
TI  - [Pd(NHC)(PR3)] (NHC = N-heterocyclic carbene) catalysed alcohol oxidation using
      molecular oxygen.
AB  - A series of [Pd(NHC)(PR(3))] complexes quantitatively form [Pd(eta(2)
      O(2))(NHC)(PR(3))] products when submitted to an dioxygen atmosphere. Synthetic
      details and structural features of these Pd-peroxo complexes are described. The
      palladium compounds were found to be efficient catalysts in the oxidation of
      alcohols into corresponding carbonyl compounds using O(2) or air as oxidant.
      Reactions proceed at low catalyst loadings with a wide range of alcohols.

PMID- 22965465
TI  - Bilateral sinonasal polyposis in a patient with unilateral choanal atresia.
AB  - Sinonasal polyposis is a disorder of hyperplastic mucosal inflammation that
      subsequently leads to the development of smooth, pale, non-neoplastic masses. The
      theories on its pathogenesis are diverse and remain debated within the medical
      community. A distinct, widely accepted, and unifying theory is absent, and
      probably unrealistic given the varying possible causes. The case reported here,
      which demonstrates nasal polyp formation within an atretic nasal cavity, suggests
      that nasal airflow or aerodynamics may have little to no effect on its etiology.
      It also seems to provide evidence that at least in some individuals nasal polyps
      appear to be due to an inflammatory disorder independent of inhalant allergen
      challenge.

PMID- 22965466
TI  - Design scheme of new tetragonal Heusler compounds for spin-transfer torque
      applications and its experimental realization.
AB  - Band Jahn-Teller type structural instabilities of cubic Mn(2)YZ Heusler compounds
      causing tetragonal distortions can be predicted by ab initio band-structure
      calculations. This allows for identification of new Heusler materials with
      tunable magnetic and structural properties that can satisfy the demands for
      spintronic applications, such as in spin-transfer torque-based devices.

PMID- 22965467
TI  - Will Switzerland follow Spain? Maybe, if you raise your voice!

PMID- 22965468
TI  - Not all floating-harbor syndrome cases are due to mutations in exon 34 of SRCAP.
AB  - Floating-Harbor syndrome (FHS) is a rare disorder characterized by short stature,
      delayed bone age, speech delay, and dysmorphic facial features. We report here
      the molecular analysis of nine cases, fulfilling the diagnostic criteria for FHS.
      Using exome sequencing, we identified SRCAP as the disease gene in two cases and
      subsequently found SRCAP truncating mutations in 6/9 cases. All mutations
      occurred de novo and were located in exon 34, in accordance with the recent
      report of Hood et al. However, the absence of SRCAP mutations in 3/9 cases
      supported genetic heterogeneity of FH syndrome. Importantly, no major clinical
      differences were observed supporting clinical homogeneity in this series of FHS
      patients.

PMID- 22965469
TI  - Association of the apolipoprotein B/apolipoprotein A-I ratio and low-density
      lipoprotein cholesterol with insulin resistance in a Chinese population with
      abdominal obesity.
AB  - The aim of this study is to assess the relationships among the apolipoprotein
      B/apolipoprotein A-I ratio (apoB/apoA-I ratio), low-density lipoprotein
      cholesterol (LDL-C) and insulin resistance (IR) in a Chinese population with
      abdominal obesity. This is a population-based, cross-sectional study of 3,945 men
      and 2,141 women with abdominal obesity. Individuals were referred to a primary
      health service and recruited for analysis. IR was measured using a homeostasis
      model assessment of insulin resistance (HOMA2-IR) with a HOMA2 calculator.
      Metabolic syndrome (MetS) was diagnosed using International Diabetes Federation
      (IDF) criteria. Comparing the apoB/apoA-I ratio and lipid indices using the HOMA2
      IR showed that the ratio, LDL-C, total cholesterol level (TC) and triglyceride
      level (TG) were higher; and the high-density lipoprotein cholesterol level (HDL
      C) was lower in the fourth than in the first quartile in both sexes (p <= 0.001).
      After adjustment for age, HOMA2-IR was positively correlated with the apoB/apoA-I
      ratio, LDL-C, TC and TG; and negatively correlated with HDL-C in men (all p <
      0.0001). HOMA2-IR was also positively correlated with the apoB/apoA-I ratio, LDL
      C, TC and TG; and negatively correlated with HDL-C in women (all p < 0.01). After
      adjustment for age and LDL-C, HOMA2-IR was found to be correlated with the
      apoB/apoA-I ratio in both men and women (r = 0.066 and 0.116, p < 0.0001). After
      adjustment for age and the apoB/apoA-I ratio, HOMA2-IR was correlated with LDL-C
      in men and women (r = 0.063 and 0.044, p < 0.0001 and p = 0.0431, respectively).
      Gender, age, LDL-C, BMI, HOMA2-IR and apoB/apoA-I were the covariates
      independently associated with presence of the MetS (Odds ratio, OR: 2.183, 1.034,
      1.013, 1.157, 1.726 and 1.570, respectively; all p < 0.05). In conclusion, the
      study showed that the apoB/apoA-I ratio and LDL-C were positively correlated with
      IR. Excluding reciprocal interactions, the apoB/apoA-I ratio and LDL-C were still
      significantly correlated with IR, but the apoB/apoA-I ratio showed a greater
      correlation with IR than LDL-C in women with abdominal obesity, compared with men
      with abdominal obesity. Both LDL-C and apoB/apoA-I were independent risk factors
      of MetS, and the apoB/apoA-I ratio was stronger in this regard than LDL-C for
      this obese population.

PMID- 22965470
TI  - Increased nitric oxide activity compensates for increased oxidative stress to
      maintain endothelial function in rat aorta in early type 1 diabetes.
AB  - Hyperglycaemia and oxidative stress are known to acutely cause endothelial
      dysfunction in vitro, but in the initial stages of diabetes, endothelium
      dependent relaxation is preserved. The aim of this study was to investigate how
      endothelium-dependent relaxation is maintained in the early stages of type 1
      diabetes. Diabetes was induced in Sprague-Dawley rats with a single injection of
      streptozotocin (48 mg/kg, i.v.), and after 6 weeks, endothelium-dependent and
      endothelium-independent relaxations were examined in the thoracic aorta in vitro.
      Lucigenin-enhanced chemiluminescence was used to measure superoxide generation
      from the aorta. Diabetes increased superoxide generation by the aorta (2,180 +/-
      363 vs 986 +/- 163 AU/mg dry tissue weight). Acetylcholine (ACh)-induced
      relaxation was similar in aortae from control (pEC(50) 7.36 +/- 0.09, R (max) 95
      +/- 3 %) and diabetic rats (pEC(50) 7.33 +/- 0.10, R (max) 88 +/- 5 %). The ACh
      induced relaxation was abolished by the combined presence of the nitric oxide
      synthase inhibitor N-nitro-L-arginine (L-NNA, 100 MUM) and an inhibitor of
      soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10
      MUM) in control rats, but under the same conditions, the diabetic aortic rings
      showed significant relaxation to ACh (pEC(50) 6.75 +/- 0.15, R (max) 25 +/- 4 %,
      p < 0.05). In diabetic aortae, the addition of haemoglobin, which inactivates
      nitric oxide, to L-NNA + ODQ abolished the response to ACh. The addition of the
      potassium channel blockers, apamin and TRAM-34, to L-NNA + ODQ also abolished the
      relaxation response to ACh. Diabetes significantly elevated plasma total
      nitrite/nitrate and increased expression of endothelial nitric oxide synthase
      (eNOS) and calmodulin in aortae. These data indicate that after 6 weeks of
      diabetes, despite increased oxidant stress, endothelium-dependent relaxation is
      maintained due to the increased eNOS expression resulting in increased NO
      synthesis. In diabetic arteries, NO acts both through and independently of cGMP
      pathways to cause relaxation.

PMID- 22965471
TI  - Desipramine prevents cardiac gap junction uncoupling.
AB  - BACKGROUND AND PURPOSE: Uncoupling of cardiac gap junction channels is an
      important arrhythmogenic mechanism in ischemia/reperfusion. Antiarrhythmic
      peptide AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH(2)) has been shown to prevent
      acidosis-induced uncoupling and ischemia-related increase in dispersion. Previous
      structure-effect investigations and subsequent computer modeling studies
      indicated that the tricyclic antidepressant desipramine may exert similar effects
      as AAP10. METHODS: We assessed the binding of (14)C-AAP10 to membranes of rabbit
      cardiac ventricles and its displacement with desipramine in a classical
      radioligand binding and competition study. Gap junction currents were measured
      between isolated pairs of human atrial cardiomyocytes under normal and acidotic
      (pH 6.3) conditions with or without 1 MUmol/l desipramine using dual whole-cell
      voltage clamp. The effect of 1 MUmol/l desipramine was assessed in isolated
      rabbit hearts (Langendorff technique) undergoing local ischemia by coronary
      occlusion with 256-channel electrophysiological mapping and subsequent analysis
      of connexin43 (Cx43) expression, phosphorylation (Western blot), and subcellular
      localization (immunohistology). RESULTS: We found saturable (14)C-AAP10 binding
      to cardiac membranes (K (D), 0.29 +/- 0.11 nmol/l; B (max), 42.5 +/- 7.2 pmol/mg)
      which could be displaced by desipramine with a K (D.High) = 0.14 MUmol/l and a K
      (D.Low) = 22 MUmol/l. Acidosis reduced the gap junction conductance in human
      cardiomyocyte pairs from 24.1 +/- 4.7 to 11.5 +/- 2.5 nS, which could be
      significantly reversed by desipramine (26.6 +/- 4.8 nS). In isolated hearts,
      ischemia resulted in significantly increased dispersion of activation-recovery
      intervals, loss of membrane Cx43, and dephosphorylation of Cx43, which all could
      be prevented by desipramine. CONCLUSION: Desipramine seems to prevent the
      uncoupling of cardiac gap junctions and ischemia-related increase in dispersion.

PMID- 22965472
TI  - Protective effects of the beta3-adrenoceptor agonist CL316243 against N-methyl-D
      aspartate-induced retinal neurotoxicity.
AB  - We have previously reported that beta(3)-adrenoceptor agonists dilate retinal
      blood vessels, but their effects on retinal neurons have been unclear. In this
      study, we examined the action of the beta(3)-adrenoceptor agonist CL316243
      against retinal damage induced by intravitreal injection of N-methyl-D-aspartate
      (NMDA) in rats. CL316243 was injected into the vitreous cavity before, with, or
      after intravitreal NMDA injection. Seven days after NMDA injection, cell loss in
      the ganglion cell layer (GCL) and thinning of the inner plexiform layer were
      observed. The reduction in the number of cells in the GCL was diminished by
      injection of CL316243 at 15, 30, 60, or 120 min after NMDA injection, whereas no
      significant protective effect was observed when CL316243 was administered 240 min
      after NMDA injection. Neither preinjection of CL316243 30 min before NMDA nor
      simultaneous injection of CL316243 with NMDA exerted any protective effect. The
      beta(3)-adrenoceptor antagonist L748337 almost completely abolished the
      protection conferred by CL316243 injection 120 min after NMDA injection. The
      number of parvalbumin-positive amacrine cells was decreased in eyes examined 1
      day after NMDA treatment, but this was prevented by CL316243 injection at 120 min
      after NMDA injection. These results suggest that CL316243 exerts protective
      effects against NMDA-induced damage by stimulation of beta(3)-adrenoceptors.
      beta(3)-adrenoceptor agonists may be effective candidates for the treatment of
      retinal diseases associated with glutamate-induced excitotoxicity, including
      glaucoma and diabetic retinopathy.

PMID- 22965473
TI  - Light induced hydrophilicity and osteoblast adhesion promotion on amorphous TiO2.
AB  - We have studied the effect of the UV induced superhydrophilic wetting of TiO(2)
      thin films on the osteoblasts cell adhesion and cytoskeletal organization on its
      surface. To assess any effect of the photo-catalytic removal of adventitious
      carbon as a factor for the enhancement of the osteoblast development, 100 nm
      amorphous TiO(2) thin layers were deposited on polyethylene terephthalate (PET),
      a substrate well known for its poor adhesion and limited wettability and
      biocompatibility. The TiO(2) /PET materials were characterized by X-ray
      photoelectron spectroscopy, and atomic force microscopy and their wetting
      behavior under light illumination studied by the sessile drop method. The
      amorphous TiO(2) thin films showed a very poor photo-catalytic activity even if
      becoming superhydrophilic after illumination. The illuminated samples recovered
      partially its initial hydrophobic state only after their storage in the dark for
      more than 20 days. Osteoblasts (HOB) were seeded both on bare PET and on TiO(2)
      /PET samples immediately after illumination and also after four weeks storage in
      darkness. Cell attachment was much more efficient on the immediately illuminated
      TiO(2)/PET samples, with development of focal adhesions and cell traction forces.
      Although we cannot completely discard some photo-catalytic carbon removal as a
      factor contributing to this cell enhanced attachment, our photodegradation
      experiments on amorphous TiO(2) are conclusive to dismiss this effect as the
      major cause for this behavior.

PMID- 22965475
TI  - Single-molecule visualization of the hybridization and dissociation of
      photoresponsive oligonucleotides and their reversible switching behavior in a DNA
      nanostructure.
AB  - A framed photo of DNA: A pair of photoresponsive oligonucleotides containing
      azobenzene moieties was introduced into double-stranded DNA within the cavity of
      a DNA nanostructure (see scheme). The two dsDNAs, in contact at the center, were
      dissociated using UV irradiation and hybridized with visible light; this was
      directly observed using high-speed atomic force microscopy.

PMID- 22965474
TI  - Isolation of entomopathogenic fungi from Northern Thailand and their production
      in cereal grains.
AB  - Spore productivity in six entomopathogenic fungal strains isolated from insect
      cadavers at four locations in Chiang Mai province was evaluated in five cereal
      grains: white-rice, wheat, rye, corn and sorghum. According to sequence analysis
      of the internal transcribed spacer regions of these isolates, they were closely
      related to Beauveria bassiana (2 isolates), Metarhizium flavoviride (1 isolate),
      Metarhizium anisopliae (1 isolate), Paecilomyces lilacinus (1 isolate) and Isaria
      tenuipes (1 isolate). Among all fungal isolates, the maximum amount of spores
      (530.0 * 10(9) conidia/g) was yielded P. lilacinus CMUCDMT02 on sorghum grain
      followed by white-rice (399.3 * 10(9) conidia/g). Moreover, the highest number of
      spore in M. flavoviride was 102.8 * 10(9) conidia/g sorghum whereas white-rice
      yielded the greatest amount of spore for B. bassiana CMUCDMF03 (141.0 * 10(9)
      conidia/g) after 60 days incubation. The fungal growth rate was found highest in
      corn for all strains and rye showed the lowest with the exception of P. lilacinus
      CMUCDMT02 among the tested grains. Spore viability was over 80 % for all isolates
      that had been inoculated for 60 days. Fungal conidia suspension of P. lilacinus
      obtained highest virulence against Bactrocera spp. at a concentration of 1 *
      10(6) spore/ml. The strains isolated, exhibited good production of conidia
      suggesting a promising strategy for the mass production of inoculum as biocontrol
      agents with low production cost.

PMID- 22965477
TI  - A new entry to the construction of a quaternary carbon center having a fluorine
      atom--S(N)2' reaction of gamma-fluoroallylic alcohol derivatives with various
      cyanocuprates.
AB  - Treatment of gamma-fluoroallylic phosphate with various lower-ordered
      cyanocuprates derived from Grignard reagents, organolithium, and organozincs gave
      the corresponding S(N)2' products having a fluorine atom at a quaternary carbon
      center in excellent yields. This system could be successfully extended to the
      chiral version, enantiomerically pure fluorine-containing materials also being
      obtained in high yield.

PMID- 22965478
TI  - The clinical significance of reduced programmed cell death 5 expression in human
      gastrointestinal stromal tumors.
AB  - Programmed cell death 5 (PDCD5) is a novel apoptosis-related gene with potent
      antitumor effects which can interact with the histone acetyltransferase Tip60 and
      induce DNA damage-induced apoptosis. Reduced PDCD5 expression has been found in a
      few types of human tumors and is also associated with the progression and
      prognosis of the tumors. However, the expression status and clinical significance
      of PDCD5 in gastrointestinal stromal tumors has not yet been analyzed. In our
      study, we examined PDCD5 expression in 63 tumor samples of gastrointestinal
      stroma at both mRNA and protein levels by RT-PCR, western blotting and
      immunohistochemistry. We found that 57% (16/28) of the tumor samples had a
      decreased PDCD5 expression at the mRNA level and 53% (35/66) of the samples were
      found to have decreased PDCD5 expression at the protein level, whereas PDCD5 was
      highly expressed in all adjacent normal gastrointestinal tissues at the mRNA or
      protein level. Moreover, decreased PDCD5 expression was significantly associated
      with clinicopathological characteristics including tumor size and mitosis. Our
      results suggest that PDCD5 expression plays a significant role in the malignant
      progression of human gastrointestinal stromal tumors and may be a key inhibitory
      factor.

PMID- 22965480
TI  - Interpolated subcutaneous fat pedicle melolabial flap for large nasal lining
      defects.
AB  - Full-thickness nasal deformities are a reconstructive challenge. Restoration of a
      reliable internal lining is critical for a successful reconstruction. Septal
      hinge flaps are the workhorse for internal lining defects. However, these and
      other intranasal mucosal flaps are sometimes unavailable due to prior harvest or
      previous oncologic resection. We present the two-stage interpolated subcutaneous
      fat pedicle melolabial flap for lining large defects when traditional intranasal
      flaps are unavailable. This approach is particularly useful when one forehead
      flap has already been expended, preserving the patient's remaining forehead
      tissue for external cover.

PMID- 22965479
TI  - Highly sensitive optical biosensor for thrombin based on structure switching
      aptamer-luminescent silica nanoparticles.
AB  - We describe here the construction of a sensitive and selective optical sensor
      system for the detection of human alpha-thrombin. The surface functionalized
      luminescent [Ru(dpsphen)(3)](4-) (dpsphen-4,7-diphenyl-1,10-phenanthroline
      disulfonate) ion doped silica nanoparticles (SiNPs) with a size ~70 nm have been
      prepared. The DABCYL (2-(4-dimethylaminophenyl)diazenyl-benzoic acid) quencher
      labeled thrombin binding aptamer is conjugated to the surface of SiNPs using
      BS(3) (bis(sulfosuccinimidyl) suberate) as a cross-linker, resulting in the
      conformational change of aptamer to form G-quadruplex structure upon the addition
      of thrombin. The binding event is translated into a change in the luminescence
      intensity of Ru(II) complex via FRET mechanism, due to the close proximity of
      DABCYL quencher with SiNPs. The selective detection of thrombin using the SiNPs
      aptamer system up to 4 nM is confirmed by comparing its sensitivity towards other
      proteins. This work demonstrates the application of simple aptamer-SiNPs
      conjugate as a highly sensitive system for the detection of thrombin and also it
      is highly sensitive towards thrombin in the presence of other proteins and
      complex medium such as BSA.

PMID- 22965481
TI  - Intralesional steroid injection for benign vocal fold disorders: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: Emerging literature had documented the potential usefulness of vocal
      fold steroid injection (VFSI) as an alternative treatment option for benign vocal
      lesions. This study aims to conduct a qualitative synthesis and quantitative meta
      analysis of vocal fold steroid injection STUDY DESIGN: Systematic review and meta
      analysis. METHODS: Electronic databases were searched using relevant keywords.
      Extracted data include author, year of publication, diagnosis, steroid regimen,
      recurrence and side effects. Reported treatment outcomes were clustered into five
      categories, i.e. subjective, perceptual, acoustic, aerodynamic, and stroboscopic.
      Meta-analyses were performed on studies with numerical results using random
      effects model. RESULTS: Six articles were identified with a total of 321
      patients. All the studies reported significant improvements after VFSI in each
      category of outcome measurements. Proposed indications for VFSI include vocal
      nodules, polyp/cyst, Reinke's edema, and scar. Meta-analysis demonstrated a
      significant increase in maximal phonation time after VFSI by 1.82 seconds
      (p<0.001, 95% confidence interval (CI): 0.29 ~ 3.35) and a 27.61 points decrease
      in voice handicap index (p<0.001, 95% CI: 16.49 ~ 38.73). Adverse effects include
      local hematoma, whitish deposition of triamcinolone, and mild vocal fold atrophy,
      which resolve spontaneously within 1 to 2 months. The recurrence rate after VFSI
      was between 4% and 31%. CONCLUSIONS: VFSI is well-tolerated under local
      anesthesia in the office setting. The invasiveness and morbidity of VFSI are low
      and the side effects are self-limited. Meta-analyses demonstrated significant
      improvements from both objective and subjective measurements. Further controlled
      studies with longer follow-up periods may evaluate the effectiveness of VFSI more
      reliably.

PMID- 22965482
TI  - Engineering protein filaments with enhanced thermostability for nanomaterials.
AB  - Self-assembling protein templates have enormous potential as biomaterials for the
      fabrication of multifunctional nanostructures that require precise positioning of
      individual molecules in regular patterns over large surface areas. Furthermore,
      the development of protein templates that are stable under extreme conditions of
      heat or chemical denaturants will expand processing conditions and end-use
      applications for biomaterials that require exceptional stability and robustness.
      In the present work, we characterized the high thermal stability of a filamentous
      protein template, the gamma-prefoldin (gammaPFD) from the hyperthermophile
      Methanocaldococcus jannaschii, and subsequently used rational design to further
      enhance the filament's thermal stability for application as a biotemplate in the
      creation of platinum nanowires. The gammaPFD assembles into long fibers with
      lengths that exceed 2 MUm, which when heated to various temperatures and examined
      by transmission electron microscopy, revealed a T(m)  of 93 degrees C for the
      quaternary filament structure. Subsequently, we increased the hydrophobicity of
      the alpha-helices of the gammaPFD's coiled-coil, which appeared to strengthen the
      filamentous structure, leading to filaments of greater length at elevated
      temperatures. These enhanced filaments functioned as templates for the synthesis
      of platinum nanowires at unprecedented temperatures, and may create new
      opportunities for other applications of nanoscale biotemplates that require
      exceptional thermal stability. See accompanying commentary by Jonathan S. Dordick
      DOI: 10.1002/biot.201200338.

PMID- 22965483
TI  - Characterization of the hypothalamus of Xenopus laevis during development. I. The
      alar regions.
AB  - The patterns of expression of a set of conserved developmental regulatory
      transcription factors and neuronal markers were analyzed in the alar hypothalamus
      of Xenopus laevis throughout development. Combined immunohistochemical and in
      situ hybridization techniques were used for the identification of subdivisions
      and their boundaries. The alar hypothalamus was located rostral to the
      diencephalon in the secondary prosencephalon and represents the rostral
      continuation of the alar territories of the diencephalon and brainstem, according
      to the prosomeric model. It is composed of the supraoptoparaventricular (dorsal)
      and the suprachiasmatic (ventral) regions, and limits dorsally with the preoptic
      region, caudally with the prethalamic eminence and the prethalamus, and ventrally
      with the basal hypothalamus. The supraoptoparaventricular area is defined by the
      orthopedia (Otp) expression and is subdivided into rostral and caudal portions,
      on the basis of the Nkx2.2 expression only in the rostral portion. This region is
      the source of many neuroendocrine cells, primarily located in the rostral
      subdivision. The suprachiasmatic region is characterized by Dll4/Isl1 expression,
      and was also subdivided into rostral and caudal portions, based on the expression
      of Nkx2.1/Nkx2.2 and Lhx1/7 exclusively in the rostral portion. Both alar regions
      are mainly connected with subpallial areas strongly implicated in the limbic
      system and show robust intrahypothalamic connections. Caudally, both regions
      project to brainstem centers and spinal cord. All these data support that in
      terms of topology, molecular specification, and connectivity the subdivisions of
      the anuran alar hypothalamus possess many features shared with their counterparts
      in amniotes, likely controlling similar reflexes, responses, and behaviors.

PMID- 22965484
TI  - The routine use of urinary pneumococcal antigen test in hospitalised patients
      with community acquired pneumonia has limited impact for adjustment of antibiotic
      treatment.
AB  - BACKGROUND: The urinary pneumococcal antigen (PnAG) test is widely used in the
      setting of community acquired pneumonia (CAP). Data regarding the impact of the
      test on antibiotic prescriptions are lacking. METHOD: The study population
      consisted of patients with suspicion of CAP in whom PnAG testing was performed.
      From November 2007 until August 2008, all patients in whom pneumococcal antigen
      testing (Binax Now(r), PnAG) was performed were evaluated. In a second period,
      from September 2008 until March 2009, we stopped PnAG testing in our institution.
      We compared the microbiological verification procedures, antibiotic prescription
      and the final diagnosis of CAP of the first period (n = 139) against the second
      period (n = 147). RESULTS: Only 139/188 patients in whom PnAG was performed had
      CAP. Of these, 22 (15%) were PnAG positive. In 11/22 patients, the diagnosis of
      pneumococcal pneumonia was additionally confirmed by positive blood and/or sputum
      culture. In only 6 of the remaining 11 patients, antibiotic treatment was changed
      as a consequence of the positive PnAG test. In cases of blood culture positive
      and in sputum positive pneumococcal pneumonia, only 8/13 (61%) and 3/15 (20%)
      were PnAG positive, respectively. The costs of the PnAG test were 188 * 42 CHF
      (in total 7,896 CHF) and no cost savings were observed. Neither with empiric nor
      with consequently prescribed antibiotic treatment was a difference found between
      the PnAG and control period. CONCLUSION: In our patient population, the routine
      Binax Now(r) PnAG testing did not lead to cost savings or narrowing of antibiotic
      prescriptions. Thus, PnAG testing should be limited to cases of diagnostic
      uncertainty where blood or sputum cultures are negative or not available.

PMID- 22965485
TI  - Dry lithography of large-area, thin-film organic semiconductors using frozen
      CO(2) resists.
AB  - To address the incompatibility of organic semiconductors with traditional
      photolithography, an inert, frozen CO(2)  resist is demonstrated that forms an in
      situ shadow mask. Contact with a room-temperature micro-featured stamp is used to
      pattern the resist. After thin film deposition, the remaining CO(2)  is sublimed
      to lift off unwanted material. Pixel densities of 325 pixels-per-inch are shown.

PMID- 22965486
TI  - Diffuse gastroduodenitis and enteritis associated with ulcerative colitis and
      concomitant cytomegalovirus reactivation after total colectomy: report of a case.
AB  - We report a rare case of peristomal pyoderma gangrenosum with severe
      gastroduodenal lesions, developing after total colectomy in a patient with
      ulcerative colitis and concomitant cytomegalovirus (CMV) enteritis. A 19-year-old
      man underwent total proctocolectomy with an ileal J-pouch anal anastomosis and
      diverting ileostomy, after 2 years of ineffective medical treatment. On
      postoperative day 6, severe peristomal pyoderma gangrenosum developed and
      progressed rapidly. Maintaining immunosuppressive therapy with corticosteroids
      for 6 days induced melena from the gastroduodenal lesions and enteritis with
      concomitant CMV reactivation. The patient required a jejunostomy, after the
      duodenal and intestinal CMV lesions had caused multiple perforations. Treatment
      with intensive cytapheresis was ineffective against the associated UC lesions,
      which healed with infliximab induction. The CMV reactivation was treated
      effectively with ganciclovir. The patient is being maintained on infliximab every
      8 weeks and there has been no sign of recurrence of the gastroduodenitis
      associated UC and CMV reactivation.

PMID- 22965487
TI  - Flavone potently stimulates an apical transporter for flavonoids in human
      intestinal Caco-2 cells.
AB  - SCOPE: Based on the studies suggesting that active transport mechanisms
      contribute to the absorption of flavonoids into human intestinal Caco-2 cells, we
      here used the structurally similar fluorescent rhodamine 123 to test a possible
      influence of flavonoids on its uptake. METHODS AND RESULTS: Rhodamine absorption
      displayed saturation kinetics with a K(m)  of 1.1 MUM and a pH-optimum of 8.5 and
      was stimulated by flavone four-fold in its V(max) . Ring C of the other 16
      flavonoids tested turned out to be of special importance in order to act as
      potent inhibitors for rhodamine transport, with a positive charge there, as
      present in the anthocyanidins, or a 2,3 double bond together with an aromatic
      ring fused to position 2, as present in flavones and flavonols, being essential
      structural requirements. Flavone-stimulated rhodamine uptake was unaffected by
      classical substrates of organic cation transporters or inhibitors of adenosine
      triphosphate (ATP)-dependent efflux pumps. Also, inhibitors of mitogen-activated
      protein kinases or tyrosine kinases did not influence the transport, whose
      stimulation, however, was essentially dependent on the simultaneous presence of
      flavone. The existence of a flavone-activated apical flavonoid transporter in
      Caco-2 cells was finally associated with the potently diminished transepithelial
      apical to basolateral fluxes of (14) C-kaempferol in the presence of competing
      unlabeled flavonoid substrates. CONCLUSION: In conclusion, flavone activates an
      as yet unidentified transporter for flavonoids in the apical membrane of Caco-2
      cells.

PMID- 22965488
TI  - Study on the interaction between gelatin and polyurethanes derived from fatty
      acids.
AB  - In this study, gelatin was blended to proprietary noncytotoxic polyurethanes (PU)
      derived from vegetable oils with different weight ratios, as material for the
      preparation of novel biomedical products. The PU/gelatin blends were
      characterized for their morphology through scanning electron microscopy.
      Mechanical and thermal properties, chemical interactions between components,
      degradation behavior, surface properties, cell adhesion, and bioactivity were
      investigated as a function of the protein content. Higher blend miscibility was
      observed for the amorphous PUs, derived from oleic acid. Properties of PU/gelatin
      films were strongly influenced by the concentration of gelatin in the films.
      Gelatin enhanced the hydrophilicity, bioactivity, and cell adhesion of PUs.

PMID- 22965489
TI  - Evaluation of new bone formation in normal and osteoporotic rats with a 3-mm
      femur defect: functional assessment with dynamic PET-CT (dPET-CT) using 2-deoxy-2
      [(18)F]fluoro-D-glucose ( (18)F-FDG) and (18)F-fluoride.
AB  - PURPOSE: The aim of the current study was to assess the formation of new bone in
      a 3-mm created defect in the femur and its adjacent bone tissue in osteoporotic
      and normal animals. The assessment is based on bone remodeling and glucose
      metabolism in a rat model with a 3-mm created defct in the femur using (18)F
      fluoride and 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) as tracers for dynamic
      PET-CT (dPET-CT). The (18)F-fluoride PET data were compared with those of (18)F
      FDG. PROCEDURES: Osteoporosis was induced by ovariectomy and a calcium restricted
      diet in each rat (n = 7). Alternatively, a sham operation was performed in the
      control group (n = 8). After 3 months, all rats were operated to create a 3-mm
      defect using an oscillating saw in the distal metaphyseal femur, which was
      internally fixed with a metal plate. Eighteen weeks after osteoporosis induction
      and 6 weeks following femoral surgery, dPET-CT studies scan were performed with
      (18)F-FDG and (18)F-fluoride. Following PET data acquisition, standardized uptake
      values (SUVs) were calculated from the tracer concentration values. Then, a two
      tissue compartmental learning-machine model was applied to the data for the
      calculation of the compartment parameters (K1-k4, VB, Ki). Furthermore, a non
      compartmental model based on the fractal dimension was applied for quantitative
      analysis of both groups and both tracers. Finally, multivariate analysis was
      performed for the statistical analysis of the kinetic data. RESULTS: The values
      for K1 and Ki were higher in the osteoporotic rats than in the control group. Ki
      and K1 of (18)F-fluoride in the adjacent bone tissue differ significantly based
      on the Wilcoxon rank-sum test for the osteoporotic and control group (p < 0.05).
      The sensitivity and the negative predictive value (NPV) based on linear
      discriminant analysis was high with a value of 100 % for both tracers and both
      evaluated regions (defect and adjacent bone tissue) when comparing control and
      osteoporotic rats. The overall accuracy with (18)F-FDG was generally higher than
      that with (18)F-fluoride for both evaluated regions for the control and
      osteoporotic rats based on a multiparameter evaluation. CONCLUSION: In this
      study, the changes in tracer kinetics accurately discriminated differences in the
      created defect in the femur and its adjacent bone tissue between osteoporotic and
      control rats.

PMID- 22965491
TI  - Timing in hip arthroscopy: does surgical timing change clinical results?
AB  - PURPOSE: To our knowledge, there is no report in the orthopaedic literature that
      correlates the duration of hip pain with the results of hip arthroscopic surgery.
      The aim of this study was to compare the modified Harris Hip Score (mHHS) with
      patient satisfaction in a prospective study over a two year period. METHODS: We
      present a prospective single-surgeon series of 525 consecutive patients
      undergoing hip arthroscopy for a labral tear, femoroacetabular impingement (FAI),
      or a chondral lesion. Modified HHS was recorded for all patients at the time of
      surgery and at six weeks, six months and one, two and three years after hip
      arthroscopy. At the time of surgery, patients were divided into three groups
      based on duration of preoperative symptoms: group A, under 6 months; group B, six
      months to three years; group C, over three years. RESULTS: Mean age was 39 years.
      There were significantly better outcomes for patients who underwent surgery
      within six months of symptom onset compared with those who waited longer.
      Patients who had symptoms for over 3 years by the time of surgery had a
      significantly poorer result than those with a shorter symptom duration and a
      higher chance of requiring revision surgery. CONCLUSIONS: We recommend that
      patients with a diagnosis of labral tear, FAI or a chondral lesion should undergo
      hip arthroscopic surgery within six months of symptom onset. Patients with
      persistent symptoms for over three years should be made aware of the poorer
      outcome after hip arthroscopy.

PMID- 22965492
TI  - Synthesis of hexahydroindoles by intramolecular C(sp3)-H alkenylation:
      application to the synthesis of the core of aeruginosins.

PMID- 22965493
TI  - Sanguinarine inhibits growth of human cervical cancer cells through the induction
      of apoptosis.
AB  - Sanguinarine, a natural benzophenanthridine alkaloid, has been shown to possess
      anticancer activity in vitro and in vivo. In the present study, we demonstrated
      that sanguinarine caused a dose-dependent inhibition of growth in HeLa and SiHa
      human cervical cancer cells, i.e., 2.43 umol/l (IC50) in HeLa cells and 3.07
      umol/l in SiHa cells. Cell cycle analysis revealed that sanguinarine
      significantly increased the sub-G1 population, from 1.7 to 59.7% in HeLa cells
      and from 1.7 to 41.7% in SiHa cells. Sanguinarine caused a dose-dependent
      decrease in Bcl-2 and NF-kappaB protein expression and a significant increase in
      Bax protein expression. Our findings indicate that sanguinarine as an effective
      anticancer drug candidate inhibits the growth of cervical cancer cells through
      the induction of apoptosis.

PMID- 22965495
TI  - Effects of alkyl chain length, solvent and tandem Claisen rearrangement on two
      dimensional structures of noncyclic isobutenyl compounds: scanning tunnelling
      microscopic study.
AB  - A series of isobutenyl compounds possessing various alkyl chain lengths (C(n)-1)
      with a carbon number of n = 14-21 were synthesized and their two-dimensional (2D)
      structures were systematically studied using scanning tunnelling microscopy (STM)
      at a highly oriented pyrolytic graphite (HOPG)/solvent interface. Two kinds of
      solvent, such as 1-phenyloctane (PO) and 1-phenylnonane (PN), were selected to
      examine the 2D structures by changing the alkyl chain length of the isobutenyl
      compounds. At the HOPG/PO interface, C(n)-1 molecules with shorter alkyl chains
      (n = 14-17) showed the same zig-zag shaped 2D structure regardless of the alkyl
      chain length, whereas an odd-even effect was recognized in C(n)-1 compounds with
      longer alkyl chains (n = 18-21) displaying the wavy and tripod structures,
      alternately. This odd-even effect was also observed at the HOPG/PN interface
      rather more distinctly. These results suggest that there is a specific alkyl
      chain length range that shows the odd-even effect in the present 2D system. After
      a tandem Claisen rearrangement (TCR), the 2D structures of all the C(n)-2
      compounds formed were converged into the same linear structure, i.e. the odd-even
      effect was cancelled by the conformational limitation induced by the TCR.

PMID- 22965496
TI  - The impact of nimodipine administration combined with nerve-muscle pedicle
      implantation on long-term denervated rat thyroarytenoid muscle.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the impact of nimodipineon reinnervation of
      the long-term denervated rat thyroarytenoid (TA) muscle following nerve-muscle
      pedicle flap (NMP) implantation. STUDY DESIGN: Quantitative histologic and
      physiologic assessments. METHODS: Using 120 Wistar rats, we performed NMP
      implantation at different times after transection of the left recurrent laryngeal
      nerve (RLN). Sixty animals received nimodipine treatment (NIMO [+] group), and
      the remaining 60 animals received no nimodipine treatment (NIMO [-] group). As a
      control, an additional 28 animals were subjected only to transection of the left
      RLN (DNV group). Subgroups were assigned based on the period after RLN
      transection (0 [immediate], 8, 16, and 32 weeks). In the DNV group, we assessed
      histologically the muscle area, axons, neuromuscular junctions (NMJs), and myosin
      heavy chains (MyHC) type IIA and IIB in the TA muscle. In the NIMO (-) and NIMO
      (+) groups, histologic assessments and evoked electromyography were performed on
      the TA muscle at 10 weeks post-NMP implantation. RESULTS: In 8-week interval
      subgroups, the muscle fiber area and the number of NMJs in the NIMO (+) group
      were significantly greater than in the NIMO (-) group (P < 0.05, each). In the 0
      week and 32-week interval subgroups, the muscle fiber subtype changed
      significantly, from IIA to IIB (P < 0.01 and P < 0.05, respectively); and, at all
      time-points the muscle fiber area, number of NMJs, and action potentials in the
      TA muscle tended to be greater in the NIMO (+) group than in the NIMO (-) group.
      CONCLUSIONS: Nimodipine expedited the effects of NMP implantation on
      reinnervation of the long-term denervated TA muscle. Laryngoscope, 2012.

PMID- 22965494
TI  - Inverted low-copy repeats and genome instability--a genome-wide analysis.
AB  - Inverse paralogous low-copy repeats (IP-LCRs) can cause genome instability by
      nonallelic homologous recombination (NAHR)-mediated balanced inversions. When
      disrupting a dosage-sensitive gene(s), balanced inversions can lead to abnormal
      phenotypes. We delineated the genome-wide distribution of IP-LCRs >1 kB in size
      with >95% sequence identity and mapped the genes, potentially intersected by an
      inversion, that overlap at least one of the IP-LCRs. Remarkably, our results show
      that 12.0% of the human genome is potentially susceptible to such inversions and
      942 genes, 99 of which are on the X chromosome, are predicted to be disrupted
      secondary to such an inversion! In addition, IP-LCRs larger than 800 bp with at
      least 98% sequence identity (duplication/triplication facilitating IP-LCRs, DTIP
      LCRs) were recently implicated in the formation of complex genomic rearrangements
      with a duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure
      by a replication-based mechanism involving a template switch between such
      inverted repeats. We identified 1,551 DTIP-LCRs that could facilitate DUP-TRP/INV
      DUP formation. Remarkably, 1,445 disease-associated genes are at risk of
      undergoing copy-number gain as they map to genomic intervals susceptible to the
      formation of DUP-TRP/INV-DUP complex rearrangements. We implicate inverted LCRs
      as a human genome architectural feature that could potentially be responsible for
      genomic instability associated with many human disease traits.

PMID- 22965497
TI  - Scalp as split thickness skin graft donor site for congenital atresia repair.
AB  - OBJECTIVE: Describe the use of the scalp as a donor site for split thickness skin
      grafts in otologic surgery. MATERIALS AND METHODS: Review of the literature with
      detailed description of surgical technique and authors' experience. RESULTS: One
      hundred and forty- four scalp split thickness skin grafts were obtained between
      2007 and 2011. No significant complications were observed with optimal cosmetic
      results. CONCLUSIONS: The scalp is a viable option as a split thickness skin
      graft donor site for otologic and other head and neck surgery. Advantages include
      improved cosmetic results at the donor site, quick healing with low complication
      rates, and easy accessibility in the operative field.

PMID- 22965498
TI  - HIV/AIDS knowledge and attitudes among Chinese college students in the US.
AB  - This study assessed knowledge and attitudes about HIV/AIDS and sources of HIV/STI
      information among Chinese college students living in the USA and explored
      specific factors associated with knowledge levels and types of sources of
      information. We surveyed 133 Chinese students enrolled in three US universities.
      About 41.4 % believed that HIV could be contracted through mosquito bites, and
      22.6 % were unaware that condoms could prevent HIV. Sources of HIV/STI
      information were the mass media. Males were more likely to demonstrate a higher
      HIV/AIDS knowledge level than females. Graduate students were more likely to cite
      television as a source of information, and less likely to mention school
      teachers, than were undergraduate students. These ethnic minority immigrant
      students held misconceptions about HIV transmission and prevention, and possibly
      utilized information of varying quality. Accordingly this study identifies
      specific objectives for education, including basic biology and diversity issues
      from evidence-based sources. 

PMID- 22965499
TI  - A culturally competent approach to exploring barriers in organ donation consent
      among Haitian immigrants: formative focus group findings and implications.
AB  - African Americans consent to donation less often than whites, have fears and
      misconceptions about donation specific to their cultures, and wait longer to
      receive transplants when the need is identified. However, there is less detailed
      empirical data on the transplant needs and barriers for Haitian immigrants. This
      paper describes focus group results designed to identify culturally grounded
      beliefs, attitudes, and barriers to organ donation. Results were used to design
      and implement the "Bay Lavi" (Give Life) campaign designed to raise awareness and
      increase organ donation consent among Haitian Immigrants. 

PMID- 22965500
TI  - Strategies for biological heart valve replacement: stentless xenografts fail to
      evolve into an alternative pulmonary valve substitute in a Ross procedure.
AB  - The Ross operation is a complex procedure for aortic valve replacement in which
      the pulmonary autograft is replaced by a homograft. However, homograft
      availability is becoming limited. This report evaluates the performance of
      porcine stentless prostheses as alternative pulmonary substitutes.
      Echocardiographic results from two patient cohorts were compared at time of
      discharge and 1 year after a Ross procedure. Thirty-three patients (median age 42
      years, range 17-62 years, 76% male) received a stentless prosthesis (median size
      25.6 mm, range 25-29 mm) for right ventricular outflow tract reconstruction.
      Clinical data were not significantly different from 106 patients (median age 47
      years, range 2-68 years, 75% male) who received cryopreserved homografts (median
      size 26 mm, range 20-33 mm). At time of discharge, peak pressure gradients
      (DeltaPmax ) across the stentless valve (median DeltaPmax 13 mmHg, range 2-26
      mmHg) were higher compared to homografts (median DeltaPmax 7 mmHg, range 1-32
      mmHg, p<0.001). At 1 year, gradients increased in both groups, but were
      significantly higher across stentless valves (median DeltaPmax 23 mmHg, range 10
      81 mmHg vs. median DeltaPmax 13 mmHg, range 2-74 mmHg, p<0.001). Eleven patients
      (33%) in the stentless-valve group were classified "at risk" with a DeltaPmax of
      >=30 mmHg. Four of them (12%) had to be re-operated. In conclusion, stentless
      valves showed higher pressure gradients and their performance was inferior to
      cryopreserved homografts. See accompanying commentary by Ulrich Stock DOI:
      10.1002/biot.201200341.

PMID- 22965501
TI  - Irritable bowel syndrome; update on pathophysiology and management.
AB  - The description of the de novo development of irritable bowel syndrome following
      an episode of bacterial gastroenteritis (pos-infectious irritable bowel syndrome)
      illustrated the potential for a luminal factor (a bacterial pathogen) to cause
      this common gastrointestinal ailment. As a consequence of these and other
      observations, as well as results of experiments involving animal models, the
      enteric flora and the immune response that it generates in the host have,
      somewhat surprisingly, come centre-stage in irritable bowel syndrome research,
      given their potential to induce the pathophysiological changes that are
      associated with irritable bowel syndrome. While evidence for immune dysfunction
      both in the mucosa and systemically continues to accumulate, methodological
      limitations have hampered a full delineation of the nature of the microbiota in
      irritable bowel syndrome. The latter is eagerly awaited and may yet provide a
      firm rationale for the use of certain probiotics and antibiotics in irritable
      bowel syndrome, whose benefits have now been described with some consistency.
      Despite its prevalence, there is a striking lack of effective therapeutic options
      for irritable bowel syndrome. While there is reason for optimism in the
      management of irritable bowel syndrome with several promising new agents
      currently undergoing clinical trials, confirmation of the efficacy and safety of
      these agents in wider patient populations is awaited. A clearer understanding of
      the physiopathologic mechanisms underlying irritable bowel syndrome, as well as
      of interrelationships between irritable bowel syndrome and other gastrointestinal
      and non-gastrointestinal disorders, will likely be required before effective drug
      therapies can be found.

PMID- 22965502
TI  - Prevalence and demographic determinants of gastroesophageal reflux disease (GERD)
      in the Turkish general population: a population-based cross-sectional study.
AB  - BACKGROUND/AIMS: We aimed to establish the prevalence and demographic
      determinants of gastroesophageal reflux disease in the Turkish general population
      using the Turkish version of the gastroesophageal reflux disease questionnaire.
      MATERIAL AND METHODS: A total of 8143 volunteers (mean age: 38.5 (13.3) years;
      52.3% males) were included in this cross-sectional questionnaire study conducted
      via face-to-face administration of the questionnaire forms including items on
      sociodemographic features, past history of gastric disorders, gastroesophageal
      reflux disease, the influence of reflux symptoms on patients' lives, physician
      visits, diagnostic tests, and reflux medications. RESULTS: A past history of
      gastric symptoms was reported in half of the population. More female participants
      (p<0.001) had a past history of gastric symptoms that yielded a previous
      diagnosis of gastroesophageal reflux disease in 19.1% of the population. The
      likelihood of gastroesophageal reflux disease was low in the majority (75.3%) of
      the subjects evaluated. Gastroesophageal reflux disease with an inconveniencing
      or disrupting impact on the patient's life was present in 17.9% and 6.8% of the
      population. Total gastroesophageal reflux disease-questionnaire scores and reflux
      prevalence were higher in older age groups (p<0.001). Females were more likely to
      have gastroesophageal reflux disease prevalence based on reflux symptoms. The
      impact of gastroesophageal reflux disease on sleep and psychological/emotional
      well-being was more pronounced in older and female patients, whereas the impact
      on eating/drinking behaviors and physical-social activities was more marked among
      females independent of their age (p<0.001). Reflux prevalence was higher in
      subjects from East Anatolia, Central Anatolia, Mediterranean, and Black Sea
      regions of Turkey (p<0.001 for each). CONCLUSIONS: Prevalence and demographic
      determinants of gastroesophageal reflux disease are compatible with the profile
      of the disease in the other Western populations, with a predilection for females
      and older individuals.

PMID- 22965503
TI  - A study on the protective activity of kefir against gastric ulcer.
AB  - BACKGROUND/AIMS: The effect of kefir on peptic ulcer disease was evaluated in an
      experimental model, with non-steroid anti-inflammatory drugs, together with the
      determination of gastric mucus secretion by quantitative digital histochemistry.
      MATERIALS AND METHODS: The experimental group included 28 male albino Wistar
      rats. After a diet with standard rat bait for 7 days, 14 rats were fed with kefir
      for 7 days while the others were kept on the same diet. At the 14th day,
      indomethacin was injected to 7 of the rats fed on kefir and to 7 of the rats on
      standard rat bait. All the rats were sacrificed after 4 hours. Gastric erosion
      and ulceration were scored histopathologically. Mucosal mucus was quantified by
      image analysis, and periodic acid-Schiff stained area percentage was determined.
      RESULTS: Erosion and ulceration were identified only in cases that received
      indomethacin. In the cases on kefir, erosion was identified in 6 cases (86%) and
      ulceration in 1 case. Rats fed on standard diet had erosion in 4 cases (57%) and
      ulceration in 3 (43%), but the difference was statistically insignificant (Mann
      Whitney test, p=0.25). The stained area percentage for gastric mucus was not
      different between the four groups (Kruskal-Wallis test, p=0.313). CONCLUSIONS:
      These findings suggest that kefir does not change gastric mucus secretion.
      Although statistically insignificant, as there were more cases with ulceration in
      cases on the rat diet, kefir might have a beneficial effect on peptic ulcer
      disease induced by non-steroid anti-inflammatory drug. This requires further
      evaluation in larger series.

PMID- 22965504
TI  - Increased anti-Echinococcus granulosus antibody positivity in Fasciola hepatica
      infection.
AB  - BACKGROUND/AIMS: Parasitic helminths express some antigen, which often accounts
      for serological cross-reactions. The aim of this study was to determine the
      prevalence of anti-Echinococcus granulosus antibody in patients with Fasciola
      hepatica infection using indirect immunofluorescence assay. MATERIALS AND
      METHODS: The study population consisted of the following groups: Fasciola
      hepatica group (n=22), hydatid disease group (n=22) and healthy control group
      (n=24). Indirect immunofluorescence assay for Echinococcus granulosus was
      performed in all groups. RESULTS: Indirect immunofluorescence assay was positive
      in all patients with hydatid disease, in 13 of 22 (59%) patients with
      fascioliasis and in 2 of 24 (8%) healthy subjects. The positivity rate of
      indirect immunofluorescence assay was significantly higher in the hydatid disease
      group compared to the fascioliasis group (p<0.001) and compared to the control
      group (p<0.001), and it was significantly higher in the fascioliasis group
      compared to the control group (p=0.001). Antibody titer was 1/100 in 7 patients,
      1/320 in 12 patients and 1/1000 in 3 patients with hydatid disease. Indirect
      immunofluorescence assay was positive in 10 of 15 patients with hepatic phase and
      in 3 of 7 patients with biliary phase of fascioliasis. The antibody titer was
      1/100 in 6 and 1/320 in 7 patients with fascioliasis. The antibody titer was
      1/100 in both healthy subjects. CONCLUSIONS: Indirect immunofluorescence assay
      for Echinococcus granulosus may be positive in a majority of patients with
      Fasciola hepatica infection and in some healthy subjects.

PMID- 22965505
TI  - Bone marrow mononuclear cell transplant therapy in mice with CCl4-induced acute
      liver failure.
AB  - BACKGROUND/AIMS: Stem cell transplantation has theoretical potential for the
      treatment of certain liver diseases. However, the use of bone marrow mononuclear
      cells as a therapy for liver disease has received little attention. The present
      study was to examine whether bone marrow mononuclear cells might be useful in the
      management of acute liver failure in an animal model. MATERIALS AND METHOTS: Bone
      marrow mononuclear cells were harvested from BALB/c mice and then labeled with
      the fluorescent dye PKH26. The labeled cells were subsequently infused into the
      tail veins of mice in which hepatic injury had been induced by CCl4 toxicity.
      After transplantation, the labeled cells in the liver were studied by fluorescent
      microscopy, and the levels of proliferating cell nuclear antigen and albumin were
      quantified in bone marrow mononuclear cell-treated and untreated groups. Serum
      aminotransferase activity was also monitored at various time points post-liver
      injury. RESULTS: Transplanted bone marrow mononuclear cells labeled with PKH26
      were found to populate the damaged liver around the portal and centrolobular
      regions, and they appeared to differentiate into albumin-producing hepatocyte
      like cells. Animals that received bone marrow mononuclear cells also showed a
      trend toward improved liver enzymes as well enhanced survival rates, relative to
      controls. CONCLUSIONS: These findings suggest that systemically delivered bone
      marrow mononuclear cells may relocate to and be retained by the injured liver;
      transplantation of bone marrow mononuclear cells showed an overall beneficial
      effect in a murine model of acute liver failure.

PMID- 22965506
TI  - AST-platelet ratio index in the prediction of significant fibrosis and cirrhosis
      in patients with chronic hepatitis B.
AB  - BACKGROUND/AIMS: We aimed to evaluate the diagnostic accuracy of AST-platelet
      ratio index in the prediction of significant fibrosis and cirrhosis in chronic
      hepatitis B patients by comparison with liver biopsy. MATERIALS AND METHODS: We
      retrospectively reviewed our computerized data of chronic hepatitis B patients
      who attended the Gastroenterology Clinic from 2004-2009. Treatment-naive chronic
      hepatitis B patients who had undergone liver biopsy were included in this study.
      The degree of fibrosis was scored according to the Ishak staging system.
      Significant fibrosis was defined as F3-6 and cirrhosis as F5-6. AST-platelet
      ratio index was calculated based on the original studies. Tests results were
      compared between the groups F0-2 versus F3-6 and F0-4 versus F5-6. RESULTS: Two
      hundred and fifty consecutive patients with chronic hepatitis B were included in
      this study. The area under the ROC curves of AST-platelet ratio index to predict
      significant fibrosis and cirrhosis were 0.779 and 0.781, respectively. Using cut
      off values <=0.5 and >1.5, significant fibrosis was excluded with a negative
      predictive value of 91.30% and sensitivity of 87.69% and predicted with a
      positive predictive value of 59.52% and specificity of 90.81% in 53.60% of
      patients. Using cut-off values <=1 and >2, cirrhosis was excluded with a negative
      predictive value of 92.09% and sensitivity of 64.10% and predicted with a
      positive predictive value of 33.33% and specificity of 91.47% in 81.60% of
      patients. CONCLUSIONS: AST-platelet ratio index may be a useful noninvasive
      marker in the exclusion of both significant fibrosis and cirrhosis in patients
      with chronic hepatitis B. However, it is not accurate in the prediction of either
      significant fibrosis or cirrhosis.

PMID- 22965507
TI  - Sclerotherapy of simple hepatic cysts by repeated aspiration and alcohol
      instillation.
AB  - BACKGROUND/AIMS: The efficacy and safety of traditional alcohol sclerotherapy
      procedures are controversial in the management of large simple hepatic cysts. In
      this study, we aimed to develop and evaluate a novel alcohol sclerotherapy
      procedure, termed repeated aspiration and alcohol instillation sclerotherapy, for
      the treatment of simple hepatic cysts. MATERIALS AND METHODS: A prospective,
      double-blind, randomized study was performed. Sixty-seven patients with large
      simple hepatic cysts were randomized into two groups to receive either single
      session alcohol retention sclerotherapy (alcohol was instilled into the cyst
      cavity, kept for 20 minutes and aspirated) or repeated aspiration and alcohol
      instillation sclerotherapy (instillation of 30-70 ml of alcohol and immediate
      aspiration with repetition 3 to 6 times until the estimated alcohol concentration
      exceeded 80%). The cyst volume reduction was calculated to compare the efficacy
      of the two procedures. We evaluated the safety of the procedure by monitoring
      side effects and assaying blood alcohol concentrations at 0, 0.5, 1, 2 and 3
      hours after sclerotherapy. RESULTS: The cyst volume reduction in patients
      undergoing repeated aspiration and alcohol instillation sclerotherapy was
      significantly higher than that in those receiving alcohol-retention
      sclerotherapy. The concentration of alcohol in the last aspirated cyst fluid was
      correlated with the mean volume reduction in patients undergoing repeated
      aspiration and alcohol instillation sclerotherapy but not in the alcohol
      retention group. Only minor side effects occurred in both groups. Although
      elevated blood alcohol concentration was noted in all patients, it declined to
      normal levels within 2-3 hours after treatment. There were no significant
      differences in blood alcohol concentration between the two groups. CONCLUSIONS:
      Repeated aspiration and alcohol instillation sclerotherapy is superior to single
      session alcohol-retention sclerotherapy in the management of large simple hepatic
      cysts.

PMID- 22965508
TI  - Documented 2009 H1N1 Influenza A infection in pediatric liver transplant patients
      -description and follow-up of 7 patients.
AB  - BACKGROUND/AIMS: There is a paucity of data regarding pediatric liver transplant
      patients from Turkey and less so globally. We report here 7 pediatric cases with
      documented H1N1 nove Influenza A infection. MATERIAL AND METHODS: 7 pediatric
      liver transplant patients on immunesuppression, tested positive with PCR for 2009
      H1N1 Influenza A, have been analyzed retrospectively. All patients were commenced
      oseltamivir treatment and 6 patients continued to take their immunosuppressive
      treatment. RESULTS: All patients (n=7) survived H1N1 novel Influenza A infection
      without any sequela. 1 patient has been admitted to Intensive Care Unit and has
      been discharged without any sequela. There was no graft dysfunction or loss
      during the infection episode. CONCLUSION: 2009 H1N1 Influenza A infection did not
      cause any mortality among our patients. Oseltamivir treatment may have played a
      role for improving in our patients' condition. Immunosuppression can be continued
      in pediatric liver transplant patients with close monitoring of vital signs and
      graft function.

PMID- 22965509
TI  - Early repeat endoscopic retrograde cholangiopancreatography: predictive factors
      and interventions required.
AB  - BACKGROUND/AIMS: Early repeat endoscopic retrograde cholangiopancreatography may
      be required due to various conditions in patients who underwent planned
      endoscopic retrograde cholangiopancreatography. We aimed to assess the factors
      leading to early repeat endoscopic retrograde cholangiopancreatography and to
      determine the patients who need closer follow-up. MATERIALS AND METHODS: A total
      of 691 patients with a mean age of 60.3+/-16.4 years who had naive papilla on
      endoscopic retrograde cholangiopancreatography were involved in the study. The
      patients who required repeat endoscopic retrograde cholangiopancreatography were
      identified. Presentations, predictive factors, treatment modalities, and outcomes
      of the patients were investigated. RESULTS: Early repeat endoscopic retrograde
      cholangiopancreatography was needed in 19 (2.7%) patients. The most common
      presentation was cholangitis in 10 (52.6%) and unresolved jaundice in 4 (21.1%).
      Multivariate analysis identified biliary stricture (p=0.024), stricture at the
      hilus (p=0.005) and unilateral drainage in the presence of hilar stricture
      (p=0.017) as the independent risk factors for early repeat endoscopic retrograde
      cholangiopancreatography. Stent migration or dysfunction was the most common
      underlying cause. Therapeutic interventions were nasobiliary drainage in 13,
      stent exchange in 4 and stone removal in 2. Additionally, percutaneous drainage
      in 4 patients, drainage of abscess in 2 patients and percutaneous drainage of
      gallbladder in 1 patient were performed. Three patients died due to their
      underlying illness. CONCLUSIONS: Unilateral stenting especially in hilar
      strictures is a predictive factor for early repeat endoscopic retrograde
      cholangiopancreatography with high mortality. These patients should be under
      close follow-up.

PMID- 22965510
TI  - Spontaneous remission of sclerosing mesenteritis.
AB  - Sclerosing mesenteritis is a rare fibroinflammatory disorder mostly affecting the
      small bowel mesentery with unknown etiology. Its clinical presentation varies
      according to the pathologic stages of sclerosing mesenteritis. In the early
      stages, nonspecific abdominal symptoms are usually seen, whereas severe small
      intestinal obstructive symptoms predominate in late stages. Diagnosis is usually
      obtained with the use of imaging techniques like computerized tomography and
      magnetic resonance imaging. Sclerosing mesenteritis is a self-limiting disease,
      and complete remission is seen in most patients. Medical and surgical treatment
      is reserved for symptomatic and complicated cases, respectively. In this paper,
      we describe a case of sclerosing mesenteritis in a 31-year-old male patient who
      presented with abdominal pain and weight loss. He was diagnosed as sclerosing
      mesenteritis with the help of two consecutive computerized tomographys. The mass
      spontaneously and completely disappeared in one month.

PMID- 22965511
TI  - Small bowel leiomyosarcoma: a case report and literature review.
AB  - Small bowel neoplasms are very uncommon, especially leiomyosarcoma of the small
      bowel. Therefore, there is often a delay before small bowel leiomyosarcoma is
      diagnosed and treatment is started. A 60-year-old Caucasian male was admitted to
      our hospital with progressive melena. Gastroscopy and colonoscopy did not reveal
      the cause of the melena, but magnetic resonance imaging showed a jejunal tumor.
      After laparoscopic resection, the tumor appeared to be a grade 2 leiomyosarcoma.
      Small bowel neoplasms can be accurately detected by magnetic resonance
      enterography or wireless capsule endoscopy. Treatment almost always consists of
      resection of the primary tumor and its metastases. The role of chemo- and
      radiotherapy is not yet clear and prognosis remains very poor, with low five-year
      survival rates.

PMID- 22965512
TI  - Plexiform schwannoma of the duodenum accompanying pyloric stenosis: report of a
      case.
AB  - Plexiform schwannoma is a benign peripheral nerve sheath tumor and is composed of
      Schwann cells arranged in a plexiform pattern. Most plexiform schwannomas are
      skin tumors, and there has been no case report of this tumor originating in the
      duodenum. We describe the first known case of plexiform schwannoma of the
      duodenum. A 60-year-old man presented with a short history of food intolerance,
      epigastric discomfort, fullness and bloatedness, sometimes vomiting, and weight
      loss, without any clinical picture of neurofibromatosis. Upper gastrointestinal
      endoscopy revealed pyloric stenosis with normal mucosal lining. The computed
      tomography demonstrated circumferentially and concentrically thickened pylorus up
      to 18 mm with narrowed lumen and limited contrast passage. Antrectomy and
      gastrojejunostomy were performed due to unknown etiology of the obstruction. The
      cut surface of the lesion revealed thickened pylorus up to 15 mm in a
      circumferential manner. It contained a 5 mm tumor consisted of multiple white
      nodules in the submucosal and subserosal layers with overlying duodenal mucosa.
      Microscopic examination revealed nodular structures composed of spindle cells
      within fascicular pattern without any atypia or mitosis. Immunohistochemical
      examination revealed that the cells diffusely and strongly expressed S100
      proteins in a nuclear and cytoplasmic pattern, but not CD117, smooth muscle
      actin, desmin, or CD34, confirming plexiform schwannoma.

PMID- 22965513
TI  - Role of imaging in gastric volvulus: stepwise approach in three cases.
AB  - In this paper, we present three cases of gastric volvulus who were admitted to
      our hospital over one year, focusing on the diagnostic process. By comparing the
      cases, we present diagnostic points and endoscopic findings that should trigger
      suspicion and lead to a prompt diagnosis by computed tomography, thus enabling
      surgery at a time before necrosis of the stomach is present. A literature review
      is also presented.

PMID- 22965514
TI  - Muir-Torre syndrome: a case report and review of the literature.
AB  - Muir-Torre syndrome is a rare autosomal dominant genodermatosis characterized by
      the occurrence of sebaceous gland neoplasm associated with visceral malignancies.
      Most patients present with sebaceous adenomas, but cystic sebaceous neoplasms
      have been reported as specific markers of the syndrome. Gastrointestinal and
      genitourinary cancers are the most common internal malignancies. Colorectal
      cancer is the commonest visceral neoplasm in Muir-Torre syndrome patients. In
      this case report, we describe a rare case of Muir-Torre syndrome associated with
      colon cancer, and we demonstrate the important role of the dermatopathologist in
      alerting the clinician to the possibility of Muir-Torre syndrome when the
      diagnosis of sebaceous neoplasm is made.

PMID- 22965515
TI  - Inflammatory myofibroblastic tumor of the stomach in an adult female--report of a
      rare case and review of the literature.
AB  - Inflammatory myofibroblastic tumor is an uncommon mesenchymal neoplasm presenting
      usually in children and young adults and reported in diverse locations including
      the lung, abdomen, retroperitoneum, pelvis, and trunk. Only a few cases involving
      the stomach have been reported, of which only 12 cases have been reported
      previously in adults. A 35-year-old female presented with complaints of abdominal
      pain, fever, vomiting, and loss of appetite for one month. Radiologically, a mass
      was seen along the greater curvature of the stomach, and was excised. Grossly, a
      well-circumscribed transmural tumor was seen involving the stomach wall.
      Histology showed a spindle cell lesion with myxoid areas and interspersed
      inflammatory cell infiltrate, immunopositive for vimentin and smooth muscle
      actin, and negative for CD34, CD117 and anaplastic lymphoma kinase-1, confirming
      a diagnosis of inflammatory myofibroblastic tumor. Inflammatory myofibroblastic
      tumor forms a rare diagnosis in the stomach and is even rarer in adults. We
      report here an extremely rare case of inflammatory myofibroblastic tumor
      involving the stomach wall in an adult, and discuss the differential diagnoses at
      this site.

PMID- 22965516
TI  - Epidermoid cyst of the cecum: a case report.
AB  - Pure, benign epidermoid cysts of the abdominal viscera are rare. There have been
      only six reports of epidermoid cysts of the cecum in the literature. A 31-year
      old female with a previous cesarean delivery was admitted to our hospital with
      inguinal pain. After admission to the hospital, she was operated with the initial
      diagnosis of adnexal mass. During the operation, no adnexal pathology was
      identified. A heterogeneous mass originated from the posterior surface of the
      cecum was observed. It had no connection with the lumen. The mass was then
      removed with dissection. Macroscopically, the mass was 9x7 cm in diameter and
      wall thickness was 0.1 cm. The inner and outer surfaces were smooth. It was
      filled with a dense yellow, thick-fatty material with no tooth, hair, bone, or
      calcification areas. On microscopic examination, the inner lining was composed of
      mature keratinized stratified squamous epithelium with a granular layer. In view
      of the later findings, the case was reported as epidermoid cyst of the cecum.
      Although epidermoid cysts are rarely seen in visceral organs, this case is the
      seventh case of cecum-originated epidermoid cyst that has been reported in the
      literature. The histogenesis of epidermoid cyst is unknown. These cysts are
      generally accepted to be sequestration cysts that may be either congenital or
      acquired. Acquired epidermoid cysts are believed to be traumatic or iatrogenic.
      The cesarean delivery may have been a cause of this condition in the present
      case. On ultrasonographic examination, these cysts can be misdiagnosed as ovarian
      cysts.

PMID- 22965517
TI  - Gastrointestinal stromal tumor of Meckel's diverticulum: a rare cause of
      intestinal volvulus.
AB  - Meckel's diverticulum is the most common congenital abnormality of the
      gastrointestinal tract. Most cases are asymptomatic; however, when symptomatic,
      it is often misdiagnosed at presentation. Common complications presenting in
      adults include bleeding, obstruction, diverticulitis, and perforation. Tumors
      within a Meckel's diverticulum are rare. Herein, we present a gastrointestinal
      stromal tumor arising from the Meckel's diverticulum that led to intestinal
      obstruction by volvulus.

PMID- 22965518
TI  - The wrong answer to the right question: misinterpretation as "prognostic factor".

PMID- 22965519
TI  - Diffuse circumferential hyperplasia of Brunner's glands causing obstruction in
      the duodenum in a 12-year-old child.

PMID- 22965520
TI  - Celiac disease presenting with intestinal obstruction: report of two cases.

PMID- 22965521
TI  - Pulse granuloma, unusual localization: appendix.

PMID- 22965522
TI  - Is central pontine myelinolysis a sign of pre-symptomatic neurologic form of
      Wilson disease?

PMID- 22965523
TI  - Metastatic liver malignant melanoma of unknown origin.

PMID- 22965524
TI  - Huge congenital epidermoid spleen cyst in an adult.

PMID- 22965525
TI  - Tuberculous peritonitis case at advanced age presenting with chylous ascites.

PMID- 22965526
TI  - Surface chemistry of grafted expanded poly(tetrafluoroethylene) membranes
      modifies the in vitro proinflammatory response in macrophages.
AB  - A series of surface-modified expanded poly(tetrafluoroethylene) membranes showed
      varied levels of in vitro macrophage proinflammatory response. Membranes
      containing a mixture of phosphate and hydroxyl groups (as determined by X-ray
      photoelectron spectroscopy analysis) stimulate greater macrophage activation than
      samples containing a mixture of phosphate and carboxylic acid segments. The types
      of proteins that adsorbed irreversibly from serum onto the two samples with the
      highest and lowest cellular response were investigated using surface-matrix
      assisted laser desorption ionisation time-of-flight mass spectrometry. Distinct
      differences in the number and type of proteins that adsorbed were observed
      between these samples. A correlation was found between the main protein
      components adsorbed onto the surfaces and the resulting in vitro proinflammatory
      response. This study strongly supports the hypothesis that the cellular response
      is not controlled directly by surface properties but is mediated by specific
      protein adsorption events. This in turn highlights the importance of better
      understanding and controlling the properties of intelligent surface-modified
      biomaterials.

PMID- 22965527
TI  - Forces created by mandibular advancement devices in OSAS patients: a pilot study
      during sleep.
AB  - BACKGROUND: The aim of this study was to measure forces created by progressive
      mandibular advancement with an oral device, during natural sleep, in a sample of
      adult patients with obstructive sleep apnea syndrome (OSAS). METHODS: A pressure
      transducer system was placed on the acrylic arms of a two-piece oral appliance
      (Herbst type) used by nine moderate to severe OSAS patients, in addition to all
      captors routinely used for polysomnography. Strains on the left and right sides
      were collected, during stable sleep stages without arousal, for each step of 1 mm
      advancement. RESULTS: The mean force in this sample was 1.18 N/mm and showed an
      almost linear evolution. Measurements showed intra- and inter-individual
      variability. CONCLUSION: The force values recorded in this study may explain the
      occlusal and skeletal side effects associated with long-term use of these oral
      appliances. They illustrate the influence of the extent of mandibular
      advancement, and indicate a possible dose-dependent effect.

PMID- 22965529
TI  - Dual-bioactivity-based liquid chromatography-coupled quadrupole time-of-flight
      mass spectrometry for NF-kappaB inhibitors and beta2AR agonists identification in
      Chinese Medicinal Preparation Qingfei Xiaoyan Wan.
AB  - Traditional Chinese medicine (TCM) preparations have been used as an effective
      multitarget strategy for the treatment of complex diseases; however, their
      bioactive constituents are undefined and difficult to identify. In this study, a
      simple and dual-target method based on ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry combined with dual
      bioactive (NF-kappaB and beta(2)-adrenergic receptor) luciferase reporter assay
      systems was developed for the rapid determination of various bioactive compounds
      of TCM preparations. Qingfei Xiaoyan Wan, a TCM preparation used for the clinical
      therapy of asthma, was analyzed with this method. Potential anti-inflammatory and
      spasmolytic constituents were screened using NF-kappaB and beta(2)-adrenergic
      receptor activity luciferase reporter assay systems and simultaneously identified
      according to the time-of-flight mass spectrometry data. One beta(2)-adrenergic
      receptor agonist (ephedrine) and four structural types of NF-kappaB inhibitors
      (arctigenin derivatives, cholic acid derivatives, chlorogenic acid, and sinapic
      acid) were characterized. Tracheloside was considered a new NF-kappaB inhibitor.
      Further cytokine and chemokine detection confirmed the anti-inflammatory effects
      of the potential NF-kappaB inhibitors. The integration of ultra-performance
      liquid chromatography/quadrupole time-of-flight mass spectrometry and dual
      bioactive human cell functional evaluation systems proved to be a simple and
      effective strategy for the rapid screening of various bioactive compounds in TCM
      preparations used to treat complex diseases.

PMID- 22965528
TI  - Expression of Pannexin1 in the outer plexiform layer of the mouse retina and
      physiological impact of its knockout.
AB  - Pannexin1 (Panx1) belongs to a class of vertebrate proteins that exhibits
      sequence homology to innexins, the invertebrate gap junction proteins, and which
      also shares topological similarities with vertebrate gap junction proteins, the
      connexins. Unlike gap junctional channels, Panx1 forms single-membrane channels,
      whose functional role in neuronal circuits is still unsettled. We therefore
      investigated the subcellular distribution of Panx1 in the mouse retina of
      wildtype and Panx1-null mice by reverse-transcription polymerase chain reaction
      (RT-PCR), immunohistochemistry, and electron microscopy. Use of Panx1-deficient
      mice served as a model to assess the physiological role of Panx1 by
      electroretinographic recordings and also to ensure the specificity of the anti
      Panx1 antibody labeling. Expression of Panx1 was found in type 3a OFF bipolar
      cells and in dendrites and axonal processes of horizontal cells. Panx1 was also
      found in horizontal cell dendrites representing the lateral elements of the triad
      synapse at cone and rod terminals. In vivo electroretinography of Panx1 knockout
      mice indicated an increased a- and b-wave compared to Panx1 wildtype mice under
      scotopic conditions. The effect on the b-wave was confirmed by in vitro
      electroretinograms from the inner retina. These results suggest that Panx1
      channels serve as sinks for extracellular current flow making them possible
      candidates for the mediation of feedback from horizontal cells to photoreceptors.

PMID- 22965530
TI  - UHPLC-DAD method for the determination of neonicotinoid insecticides in single
      bees and its relevance in honeybee colony loss investigations.
AB  - In the understanding of colony loss phenomena, a worldwide crisis of honeybee
      colonies which has serious consequences for both apiculture and bee-pollination
      dependent farm production, analytical chemistry can play an important role. For
      instance, rapid and accurate analytical procedures are currently required to
      better assess the effects of neonicotinoid insecticides on honeybee health. Since
      their introduction in agriculture, neonicotinoid insecticides have been blamed
      for being highly toxic to honeybees, possibly at the nanogram per bee level or
      lower. As a consequence, most of the analytical methods recently optimized have
      focused on the analysis of ultratraces of neonicotinoids using liquid
      chromatography-mass spectrometry techniques to study the effects of sublethal
      doses. However, recent evidences on two novel routes-seedling guttations and seed
      coating particulate, both associated with corn crops-that may expose honeybees to
      huge amounts of neonicotinoids in the field, with instantly lethal effects,
      suggest that selected procedures need optimizing. In the present work, a
      simplified ultra-high-performance liquid chromatography-diode-array detection
      method for the determination of neonicotinoids in single bees has been optimized
      and validated. The method ensures good selectivity, good accuracy, and adequate
      detection limits, which make it suitable for the purpose, while maintaining its
      ability to evaluate exposure variability of individual bees. It has been
      successfully applied to the analysis of bees in free flight over an experimental
      sowing field, with the bees therefore being exposed to seed coating particulate
      released by the pneumatic drilling machine.

PMID- 22965531
TI  - Molecular characterization of dissolved organic matter (DOM): a critical review.
AB  - Advances in water chemistry in the last decade have improved our knowledge about
      the genesis, composition, and structure of dissolved organic matter, and its
      effect on the environment. Improvements in analytical technology, for example
      Fourier-transform ion cyclotron (FT-ICR) mass spectrometry (MS), homo and hetero
      correlated multidimensional nuclear magnetic resonance (NMR) spectroscopy, and
      excitation emission matrix fluorimetry (EEMF) with parallel factor (PARAFAC)
      analysis for UV-fluorescence spectroscopy have resulted in these advances.
      Improved purification methods, for example ultrafiltration and reverse osmosis,
      have enabled facile desalting and concentration of freshly collected DOM samples,
      thereby complementing the analytical process. Although its molecular weight (MW)
      remains undefined, DOM is described as a complex mixture of low-MW substances and
      larger-MW biomolecules, for example proteins, polysaccharides, and exocellular
      macromolecules. There is a general consensus that marine DOM originates from
      terrestrial and marine sources. A combination of diagenetic and microbial
      processes contributes to its origin, resulting in refractory organic matter which
      acts as carbon sink in the ocean. Ocean DOM is derived partially from humified
      products of plants decay dissolved in fresh water and transported to the ocean,
      and partially from proteinaceous and polysaccharide material from phytoplankton
      metabolism, which undergoes in-situ microbial processes, becoming refractory.
      Some of the DOM interacts with radiation and is, therefore, defined as
      chromophoric DOM (CDOM). CDOM is classified as terrestrial, marine,
      anthropogenic, or mixed, depending on its origin. Terrestrial CDOM reaches the
      oceans via estuaries, whereas autochthonous CDOM is formed in sea water by
      microbial activity; anthropogenic CDOM is a result of human activity. CDOM also
      affects the quality of water, by shielding it from solar radiation, and
      constitutes a carbon sink pool. Evidence in support of the hypothesis that part
      of marine DOM is of terrestrial origin, being the result of a long-term carbon
      sedimentation, has been obtained from several studies discussed herein.

PMID- 22965532
TI  - Microextraction techniques combined with capillary electrophoresis in
      bioanalysis.
AB  - Over the past two decades, many environmentally sustainable sample-preparation
      techniques have been proposed, with the objective of reducing the use of toxic
      organic solvents or substituting these with environmentally friendly
      alternatives. Microextraction techniques (MEs), in which only a small amount of
      organic solvent is used, have several advantages, including reduced sample
      volume, analysis time, and operating costs. Thus, MEs are well adapted in
      bioanalysis, in which sample preparation is mandatory because of the complexity
      of a sample that is available in small quantities (mL or even MUL only).
      Capillary electrophoresis (CE) is a powerful and efficient separation technique
      in which no organic solvents are required for analysis. Combination of CE with
      MEs is regarded as a very attractive environmentally sustainable analytical tool,
      and numerous applications have been reported over the last few decades for
      bioanalysis of low-molecular-weight compounds or for peptide analysis. In this
      paper we review the use of MEs combined with CE in bioanalysis. The review is
      divided into two sections: liquid and solid-based MEs. A brief practical and
      theoretical description of each ME is given, and the techniques are illustrated
      by relevant applications.

PMID- 22965533
TI  - Simultaneous control of carriers and localized spins with light in organic
      materials.
AB  - An organic insulating crystal reversibly becomes a magnetic conductor under UV
      irradiation. The rapid and qualitative change in the physical properties is
      wavelength selective and explained by charge transfer between donor and
      photochemically active acceptor molecules. The photochemical redox reaction in
      the crystal produces a partially filled band and localized spins simultaneously.

PMID- 22965534
TI  - Treatment for critical lower limb ischemia in elderly patients.
AB  - BACKGROUND: Critical limb ischemia (CLI) has a poor outcome when left untreated.
      The benefits of revascularization in the very elderly might be limited because of
      co-morbidities and short life expectancy. Therefore, optimal management of CLI in
      the elderly is not straightforward. We analyzed treatment results for elderly
      patients with CLI (Rutherford 4 or 5/6) in our clinic. METHODS: Hospital charts
      of all patients>70 years of age diagnosed with Rutherford stage 4-6 peripheral
      arterial disease between January 2006 and December 2009 were reviewed. We divided
      patients into two age groups (70-79 and >=80 years) to compare treatment results.
      Primary interventions were defined as conservative, endovascular, reconstructive
      surgery, and amputation. Outcome measures were mortality, reintervention, and
      major amputation rates. RESULTS: There were 191 patients [99 (52%) were women],
      median age 78.4 years, range 70-98 years. Altogether, 119 (62%) patients were
      aged 70-79 years, and 72 (38%) were >=80 years. The primary intervention was
      equally divided over the two age groups (p=0.21). Trans-Atlantic Inter-Society
      Consensus Document on Management of Peripheral Arterial Disease (TASC II)
      classifications of aortoiliac lesions were not significantly different regarding
      intervention (p=0.62) or age (p=0.39). TASC II classification of femoropopliteal
      lesions was significantly different relative to intervention (p<0.01) but not
      different between age groups (p=0.68). Mortality rate after reconstructive
      surgery was significant higher in the oldest age group (p<0.01). After
      conservative treatment, endovascular treatment, or amputation, the mortality
      rates were not significantly different between the two age groups (respectively,
      p=0.06, p=0.33, p=0.76). Reintervention rate was 51% in the 70- to 79-year group
      compared to 32% in the >=80-year group. After initial treatment, major
      amputations were performed in 10% in the 70- to 79-year group compared to 13% in
      the >=80-year group. CONCLUSIONS: In patients aged>=80 years, surgical
      revascularization resulted in a significant higher mortality rate in our clinic,
      whereas primary conservative, endovascular treatment and amputation resulted in
      similar mortality in both age groups. When considering surgical revascularization
      in the very elderly, surgeons should focus on careful patient selection.

PMID- 22965535
TI  - Increased resection rates and survival among patients aged 75 years and older
      with esophageal cancer: a Dutch nationwide population-based study.
AB  - BACKGROUND: The incidence of esophageal cancer has grown over the recent decades
      and 30% of esophageal cancer patients are now 75 years or older at the time of
      diagnosis. The aim of this study was to evaluate trends in management and
      survival of patients aged 75 years or older with esophageal cancer. METHODS: In
      the Netherlands cancer registry, we identified all patients aged 75 years or
      older who were diagnosed with esophageal cancer between 1989 and 2008. Trends in
      management and survival were analyzed by time period (1989-2001 vs. 2002-2008),
      TNM stage, and age (75-79, 80-84, and 85+ years). chi2 testing was used to
      analyze time trends in treatment, Kaplan-Meier analysis and log-rank testing to
      estimate survival, and Cox regression model to calculate hazard ratios for death.
      RESULTS: Some 7,253 patients were included in the study. The surgical resection
      rate increased over the 1989-2008 period from 8.9 to 12.6% (p=0.028), especially
      among patients aged 75-79 years (44.6 vs. 55.4%, p<0.001) and patients with TNM
      stage I disease (12.7 vs. 22.0%, p<0.001). The use of definitive
      chemoradiotherapy (CRT) also increased (0.19 vs. 2.20%, p<0.001). Whereas the use
      of chemotherapy as a single-modality treatment more than doubled (0.64 vs. 1.54%,
      p=0.004), that of radiotherapy alone decreased (38.1 vs. 31.6%, p<0.001).
      Although median survival time was marginally higher in the 2002-2008 period than
      in 1989-2001, overall 5 year survival rates remained low at 6 and 5%,
      respectively (p<0.001). Five-year survival rate after surgery increased from 16
      to 30% (p<0.001). CONCLUSIONS: In patients of 75 years or older, surgical
      treatment and use of definitive CRT have increased between 1989 and 2008. Also,
      an increase in the use of chemotherapy as a single modality was noted. Overall 5
      year survival for all cancer patients was stable but remained poor, while
      survival of patients who underwent esophagectomy improved significantly in the
      Netherlands since 1989.

PMID- 22965536
TI  - Assessment of liver stiffness measurement: novel intraoperative blood loss
      predictor?
AB  - BACKGROUND: The risks of massive intraoperative blood loss are of major concern
      during liver surgery. Various predictors of massive intraoperative blood loss
      were reported for identifying patients preoperatively with high risk of suffering
      massive intraoperative blood loss during liver surgery. The assessment of the
      extent of fibrosis may be a way to predict the risk of the intraoperative blood
      loss in patients undergoing liver surgery. Liver stiffness measurement by
      transient elastography is a noninvasive method for assessing liver fibrosis in
      patients with chronic liver disease. The purpose of this retrospective, single
      center study was to assess a correlation between liver stiffness measurement and
      intraoperative blood loss during liver surgery for determining the role of liver
      stiffness measurement as a predictor of intraoperative blood loss. METHODS: A
      total of 45 patients who underwent elective right hepatectomy from August 2007 to
      July 2011 were selected. Liver stiffness measurement, tumor size, intraoperative
      data, and perioperative laboratory data were retrospectively investigated.
      Correlation analysis was used to find the correlations between variables.
      RESULTS: Among the 45 patients enrolled in this study, 43 were ultimately
      investigated. A statistically positive correlation was found between the
      intraoperative blood loss and the median liver stiffness measurements (r = 0.420,
      p = 0.005). CONCLUSIONS: The liver stiffness measurement is a possible predictor
      of intraoperative blood loss through the correlation between liver stiffness
      measurement and the intraoperative blood loss during right hepatectomy.

PMID- 22965537
TI  - Portal venous system thrombosis after pancreatic resection.
AB  - BACKGROUND: Portal venous system thrombosis (PVST) is a rare, potentially fatal
      complication after pancreatic resection. The aim of this study was to assess the
      incidence, presenting symptoms, management, and treatment of PVST in a large
      cohort of patients. METHODS: Prospectively collected data on patients undergoing
      pancreatic resection between 1997 and 2009 were reviewed retrospectively.
      Preoperative and postoperative imaging were analyzed for the presence or absence
      of venous thrombi. All patients received standard thromboprophylaxis with low
      molecular-weight heparin (LMWH). RESULTS: Of 516 pancreatic resections performed,
      18 (3.5 %) were complicated by PVST. The most common clinical presentations were
      abdominal pain (n = 9) and ascites (n = 5) but never any alarm symptoms. Other
      symptoms were vague and nonspecific (e.g., weight loss, fatigue, fever). Total
      pancreatectomy was a risk factor compared to hemipancreatectomy (p < 0.01),
      whereas the underlying disease per se did not make any difference. The median
      interval between surgery and diagnosis of PVST was 105 days (range 1-1,440 days).
      PVST was at least a contributing factor in the postoperative deaths of two
      patients. LMWH therapy did not significantly affect survival. CONCLUSIONS: PVST
      remains a relatively infrequent complication after pancreatic resection. Because
      accurate diagnosis and timely intervention may reduce morbidity and mortality,
      the possibility of PVST should be considered in patients presenting with vague
      symptoms. Whether anticoagulant treatment is needed is still not clear; there
      were no obvious differences in outcome between treated and untreated patients.

PMID- 22965538
TI  - Does hepatic ischemia-reperfusion injury induced by hepatic pedicle clamping
      affect survival after partial hepatectomy for hepatocellular carcinoma?
AB  - BACKGROUND: Liver resection offers a chance of cure for patients with
      hepatocellular carcinoma (HCC). Hepatic pedicle clamping (HPC) is commonly used
      to reduce blood loss during hepatectomy. Hepatic ischemia-reperfusion (I/R)
      injury has recently been reported to be a major factor in accelerated tumor
      growth. We therefore evaluated the effect of intermittent HPC on the prognosis of
      patients after liver resection. METHODS: The clinicopathological features and
      serum/tissue samples of 386 HCC patients who underwent curative liver resection
      were prospectively collected. The patients were divided into the HPC group (over
      30 min) and the non-HPC group. Disease-free survival and overall survival were
      analyzed using multivariate analyses, Kaplan-Meier curves, and log-rank tests.
      Matrix metalloproteinases and E-selectin were measured to study hepatic I/R
      injury. RESULTS: The preoperative clinicopathological data were comparable
      between the HPC group (n = 224) and the non-HPC group (n = 162). During the study
      period, 257 of the 386 patients (66.6 %) developed tumor recurrence. The overall
      tumor recurrence and intrahepatic tumor recurrence rates were not significantly
      different between the two groups. There were no significant differences between
      the two groups with respect to the 1-, 3-, and 5-year disease-free and overall
      survival rates. Similarly, subgroup analyses also showed no marked difference in
      survival rates for patients with cirrhosis in the two groups. The levels of mRNA
      in liver tissues and serum concentrations of MMP-2, MMP-9, and E-selectin showed
      no significant differences between the pre- and post-occlusion periods.
      CONCLUSIONS: Intermittent HPC produced no adverse effect on disease-free and
      overall survival for patients who underwent liver resection for HCC.

PMID- 22965539
TI  - The elusive silyliumylidene [ClSi:]+ and silathionium [ClSi=S]+ cations
      stabilized by bis(iminophosphorane) chelate ligand.

PMID- 22965540
TI  - Effects of extra-embryonic provisioning on larval morphology and histogenesis in
      Boccardia proboscidea (Annelida, Spionidae).
AB  - Morphology is strongly correlated with trophic mode in marine invertebrate
      larvae. We asked if larval morphogenesis is influenced by adelphophagy, a trophic
      mode in which larvae are provisioned with additional yolk in the form of extra
      embryonic nurse eggs, instead of the more common increase in egg size. We used
      histology and scanning electron microscopy to analyze morphogenesis in Boccardia
      proboscidea, a polychaete that produces both small planktotrophic larvae and
      large adelphophagic larvae in a single egg capsule. Results indicate that both
      morphs are similar for histogenesis of ectodermal derivatives, and differ for the
      gut mucosa and coelom which show delayed differentiation in the adelphophagic
      morph. Heterochrony in gut and coelom development suggests that differentiation
      of these organ systems is decoupled from overall development, and that a trade
      off exists between maturation of these tissues and rapid growth. We also looked
      for potential barriers to adelphophagy in planktotrophic larvae that have nurse
      eggs available to them. These planktotrophic larvae appeared morphologically
      equipped for adelphophagy: the gut was differentiated at an early stage, and
      larvae had structures involved in nurse-egg ingestion in the adelphophagic morph
      (e.g., oral cilia and ventral ciliated patches). Planktotrophic larvae were
      additionally capable of ingesting particles (Di-I) while in the egg capsule. Lack
      of adelphophagy in planktotrophic larvae remains enigmatic but these results
      indicate that morphology alone does not account for the arrested development
      shown by these larvae.

PMID- 22965541
TI  - Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR
      122 in rats.
AB  - SCOPE: One major health problem in westernized countries is dysregulated fatty
      acid and cholesterol metabolism that causes pathologies such as metabolic
      syndrome. Previous studies from our group have shown that proanthocyanidins,
      which are the most abundant polyphenols in the human diet, regulate lipid
      metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and
      miR-122, regulate genes that are involved in lipid metabolism. METHODS AND
      RESULTS: Here, we show that grape seed proanthocyanidins rapidly and transiently
      repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in
      vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR
      122 target gene fatty acid synthase were also modulated by proanthocyanidins.
      Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and
      fatty acid synthase mRNA and protein levels were reduced after the miRNA levels
      were altered. CONCLUSION: These results suggest that proanthocyanidin treatment
      increased hepatic cholesterol efflux to produce new HDL particles by repressing
      miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight
      a new mechanism by which grape seed proanthocyanidins produce hypolipidemia
      through their effects on miRNA modulators of lipid metabolism.

PMID- 22965542
TI  - Chronic sinus disease and epidural abscess: Gemella morbillorum as emerging cause
      of central nervous system infections.

PMID- 22965543
TI  - The dissipation of three fungicides in a biobed organic substrate and their
      impact on the structure and activity of the microbial community.
AB  - Biopurification systems (BPS) have been introduced to minimise the risk for point
      source contamination of natural water resources by pesticides. Their depuration
      efficiency relies mostly on the high biodegradation of their packing substrate
      (biomixture). Despite that, little is known regarding the interactions between
      biomixture microflora and pesticides, especially fungicides which are expected to
      have a higher impact on the microbial community. This study reports the
      dissipation of the fungicides azoxystrobin (AZX), fludioxonil (FL) and
      penconazole (PC), commonly used in vineyards, in a biomixture composed of pruning
      residues and straw used in vineyard BPS. The impact of fungicides on the
      microbial community was also studied via microbial biomass carbon, basal
      respiration and phospholipid fatty acid analysis. AZX dissipated faster (t1/2 =
      30.1 days) than PC (t1/2 = 99.0 days) and FL (t1/2 = 115.5 days). Fungicides
      differently affected the microbial community. PC showed the highest adverse
      effect on both the size and the activity of the biomixture microflora. A
      significant change in the structure of the microbial community was noted for PC
      and FL, and it was attributed to a rapid inhibition of the fungal fraction while
      bacteria showed a delayed response which was attributed to indirect effects by
      the late proliferation of fungi. All effects observed were transitory and a full
      recovery of microbial indices was observed 60 days post-application. Overall, no
      clear link between pesticide persistence and microbial responses was observed
      stressing the complex nature of interactions between pesticides in microflora in
      BPS.

PMID- 22965545
TI  - Osteoblasts response to nylon 6,6 blended with single-walled carbon nanohorn.
AB  - Bioactivity is an important aspect that can be appropriately used to tune the
      cellular interactions occurring at the biomaterial-physiological interface. In
      this regard, we explore here the nano- or quantum-size effects of a highly
      dispersible nanostructured carbon present in the void space between the polymers
      chains (Nylon 6,6) in modulating the cellular functions when osteoblasts are
      seeded on biocompatible substrates. The filling-up of void space in polymer
      facilitates filopodia to access the extracellular matrix, enabling integrin
      receptors to bind to the artificial biomedical device, promoting cellular
      interactions. In this regard, the fundamental principles of materials processing
      and cellular biology were combined to elucidate the mechanism of cell-substrate
      interactions and the molecular machinery controlling the cell response. This is
      accomplished by investigating cell attachment, proliferation, and morphology,
      including cytomorphometry evaluation and quantitative assessment of prominent
      proteins, actin, vinculin, and fibronectin that are sensitive to cell-substrate
      interactions.

PMID- 22965544
TI  - Measurement of personal and integrated exposure to particulate matter and co
      pollutant gases: a panel study.
AB  - Personal exposure measurement can serve as an effective tool to understand the
      effect of exposure to air pollutants. Alternatively, exposure assessment using
      pollutant concentrations in different microenvironments and accurate time
      activity information for the subjects can provide good information regarding
      human integrated exposure. A panel of 18 healthy students of Indian Institute of
      Technology (IIT) Kanpur in the age group of 18 to 30 years participated in the
      personal exposure measurements for particulate matter, CO, NO(2) and VOC during
      post-monsoon and pre-monsoon seasons. Overall, 432 h person exposure data was
      collected in this study. The major sources of particulate and gaseous co
      pollutants were identified. These directly obtained personal exposure values were
      then compared to the indirectly estimated integrated exposure values. Personal
      and integrated exposures gave statistically similar results. Through this study,
      we have shown that integrated exposure values could closely estimate the personal
      exposure values for particulate matter that can significantly reduce time and
      cost involved in personal exposure studies. The lung parameters for all the
      subjects measured during the pre-monsoon and post-monsoon seasons showed
      statistically significant reduction during pre-monsoon. This was attributed to
      the high levels of coarse particles during pre-monsoon.

PMID- 22965546
TI  - Morphology of the tongue dorsal surface of gilthead seabream (Sparus aurata).
AB  - The gilthead seabream is a food fish, one of the most frequently used in
      aquaculture. In the species of commercial interest, feeding in captivity is very
      important and this process is strictly related to the morphological
      characteristics of the oral cavity. The aim of this study is, using the standard
      procedures for light and scanning electron microscopy, to analyze the morphology
      of the tongue dorsal surface to show if relationships are present between the
      tongue morphology and the nutritional habits and choices of this farmed species.
      The main characteristic of the gilthead seabream oral cavity floor is the
      presence of an apical pouch, with, probably, a protective role mainly for the
      apical, free part of the tongue. Three zones, like in other teleosts, an apex, a
      body and a root, can be clearly distinguished. In the pouch foliate-like papillae
      were observed, while the whole tongue is characterized by the presence of two
      types of papillae, respectively with a fungiform and cylindroid aspect, both
      randomly distributed throughout the whole dorsal surface of the tongue. Scattered
      and numerous taste buds, with the typical pear-onion shape, together with small
      and numerous taste pores are also present, distributed throughout the tongue
      surface. Our results demonstrate that in the gilthead seabream important mechanic
      and sensory roles are carried out by specific anatomical structures. Our
      anatomical data could give, together with further biochemical and physiological
      data, an important support with the aim of improving the nutrition of aquaculture
      species.

PMID- 22965547
TI  - Quantitative airway analysis during drug-induced sleep endoscopy for evaluation
      of sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To quantitatively measure changes in airway caliber at
      multiple anatomical levels during drug-induced sleep endoscopy (DISE) for
      evaluation of sleep apnea. We hypothesize that patients undergoing DISE will
      show: 1) collapse at multiple upper airway regions (retropalatal, retroglossal,
      and retroepiglottic), with greater collapse in the retropalatal region; and 2)
      greater anterior-posterior dimensional narrowing than the lateral. STUDY DESIGN:
      Case series. METHODS: Patients underwent DISE employing propofol as part of a
      nonrandomized prospective trial assessing candidacy for transoral robotic surgery
      intervention for sleep apnea. Images of the retropalatal, retroglossal, and
      retroepiglottic regions were captured during an initial period of light sedation
      and again in a period of deep sedation. Images were analyzed using software to
      measure the percent change in regional airway measurements as a result of DISE.
      RESULTS: Thirty-seven sleep endoscopy videos were analyzed from patients with
      obstructive sleep apnea (apnea-hypopnea index: 42.9 +/- 27.0 events/hour).
      Analyzable images were in the retropalatal (n = 24), retroglossal (n = 27), and
      retroepiglottic (n = 29) regions. The patients demonstrated mean reductions in
      airway area in the retropalatal (84.1 +/- 18.7%), retroglossal (39.3 +/- 37.5%),
      and retroepiglottic region (44.6 +/- 42.8%). No statistically significant
      differences were found between lateral and anterior-posterior airway dimensional
      changes. CONCLUSIONS: Patients undergoing DISE had significant reductions in
      airway area at multiple regions under deep sedation with propofol. We conclude
      that collapse in the retropalatal region is greater than the hypopharyngeal
      region. This method can be used to quantitatively measure DISE upper airway
      changes, which could potentially be used as a means for understanding surgical
      outcomes in patients with sleep apnea.

PMID- 22965548
TI  - Phytochemical profile and apoptotic activity of Onopordum cynarocephalum.
AB  - A phytochemical investigation of acetone and chloroform extracts of the aerial
      parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to
      the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the
      eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13
      sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by
      spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect
      against three human melanoma cell lines, M14, A375, and A2058, of the different
      extracts and compounds of O. cynarocephalum was also investigated. Among them,
      the chloroform extract exhibited the strongest biological activity, while the
      most active compounds were the lignan arctigenin (1), and the sesquiterpenes,
      compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the
      eudesmane type. Our data also demonstrate that acetone and chloroform extracts
      induce, in the A375 cell line, apoptotic cell death that could be related to an
      overall action of the compounds present, but in particular to the lignans
      arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these
      molecules were able to induce a high DNA fragmentation, correlated to a
      significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis
      appears to be mediated, at least in part, via PTEN activity and the inhibition of
      Hsp70 expression.

PMID- 22965549
TI  - Keeping your balance while balancing a cylinder: interaction between postural and
      voluntary goals.
AB  - The present study investigated whether postural responses are influenced by the
      stability constraint of a voluntary, manual task. We also examined how task
      constraint and first experience (the condition with which the participants
      started the experiment) influence the kinematic strategies used to simultaneously
      accomplish a postural response and a voluntary task. Twelve healthy, older adults
      were perturbed during standing, while holding a tray with a cylinder placed with
      the flat side down (low constraint, LC) or with the rolling, round side down
      (high constraint, HC). Central set changed according to the task constraint, as
      shown by a higher magnitude of both the gastrocnemius and tibialis anterior
      muscle activation bursts in the HC than in the LC condition. This increase in
      muscle activation was not reflected, however, in changes in the center of
      pressure or center of mass displacement. Task constraint influenced the peak
      shoulder flexion for the voluntary tray task but not the peak hip flexion for the
      postural task. In contrast, first experience influenced the peak hip flexion but
      not the peak shoulder flexion. These results suggest an interaction between two
      separate control mechanisms for automatic postural responses and voluntary
      stabilization tasks.

PMID- 22965550
TI  - Dynamics of inter-modality re-weighting during human postural control.
AB  - Flexible and stable postural control requires adaptation to changing
      environmental conditions, a process which requires re-weighting of multisensory
      stimuli. Recent studies, as well as predictions from a computational model, have
      indicated a reciprocal re-weighting relationship between modalities when a
      sensory stimulus changes amplitude. As one modality is down-weighted, another is
      up-weighted to compensate (and vice versa). The purpose of this study was to
      investigate the dynamics of intra- and inter-modality re-weighting process by
      examining postural responses to manipulation of proprioception and visual
      modalities simultaneously. Twenty-two young adults were placed in a visual cave
      and stood on a variable-pitch platform for thirteen trials of 250 s apiece. The
      platform was rotated at constant frequency of 0.4 Hz and amplitudes of 0.3 (low)
      or 1.5 (high) degrees. Platform amplitude was manipulated in two conditions: low
      to-high or high-to-low. The visual stimulus was displayed at constant frequency
      of 0.35 Hz and amplitude of 0.08 degrees. The results showed both fast and slow
      changes in center of mass (CoM) response to the switch in platform amplitude. On
      both timescales, CoM response changed in a reciprocal manner relative to platform
      amplitude. When the platform amplitude increased (low-to-high condition), CoM
      response decreased relative to the platform and increased relative to the visual
      stimulus, indicating both intra-modality and inter-modality sensory re-weighting.
      In the high-to-low condition, however, there was no change in CoM response
      relative to visual stimulus, indicating that re-weighting may also be dependent
      on the absolute level of gain. Sway variability at frequencies other than the
      stimulus frequency also showed a reciprocal relationship with CoM gain relative
      to platform. Overall, these results indicate that dynamics of multisensory re
      weighting is clearly more complicated than the schemes proposed by current
      adaptive models of human postural control.

PMID- 22965551
TI  - Self-enhancement processing in the default network: a single-pulse TMS study.
AB  - Much research has been done on positive self-evaluation and its relationship to
      mental health. However, little is known about its neural underpinnings. Imaging
      studies have suggested that the brain's default network is involved with self
      related processing and that one portion of the default network, medial prefrontal
      cortex (MPFC), is particularly involved with self-evaluation. Here, we used
      transcranial magnetic stimulation (TMS) to causally demonstrate that this
      network, and particularly MPFC, is involved with self-evaluative processing. In a
      first experiment, 27 healthy volunteers judged whether adjectives, evenly divided
      between desirable and undesirable traits, described themselves or their best
      friends, and a robust self-enhancement bias effect was found. In a second
      experiment, single-pulse TMS was applied targeting three locations (MPFC and left
      and right parietal cortex) in a different group of healthy volunteers while they
      performed the adjective task. In each trial, TMS was applied at one of five
      different times relative to onset of the adjective ranging from 0 to 480 ms. TMS
      affected self-enhancement bias in a site- and latency-specific manner: at MPFC,
      the self-enhancement bias actually reversed at 160 ms, with subjects favoring
      their best friend over themselves. TMS may thus be of use in investigating areas
      of mental illness in which self-evaluation is abnormal, potentially as a
      diagnostic tool. In addition, the present study, combined with our previous
      reports (Lou et al., Proc Natl Acad Sci USA 101(17):6827-6832, 2004, Exp Brain
      Res 207:27-38, 2010), causally demonstrates two kinds of self-related processing
      within the default network, one centered in parietal cortex and concerned with
      retrieval of self-related associations, and the other MPFC-centered and involved
      in self-evaluative processing.

PMID- 22965553
TI  - A functional-group-tolerant catalytic trans hydrogenation of alkynes.
AB  - Against the rules: during the hundred years following Sabatier's groundbreaking
      work on catalytic hydrogenation, syn delivery of the H atoms to the pi system of
      a substrate remained the governing stereochemical rule. An exception has now be
      found with the use of cationic [Cp*Ru] templates, which accounts for the first
      practical, functional-group-tolerant, broadly applicable and highly E-selective
      semihydrogenation method for alkynes.

PMID- 22965552
TI  - Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and
      erythroid progenitor in 5q- syndrome and in Diamond-Blackfan anemia.
AB  - Friend leukemia virus integration 1 (Fli1) and erythroid Kruppel-like factor
      (EKLF) participate under experimental conditions in the differentiation of
      megakaryocytic and erythroid progenitor in cooperation with other transcription
      factors, cytokines, cytokine receptors, and microRNAs. Defective erythropoiesis
      with refractory anemia and effective megakaryopoiesis with normal or increased
      platelet count is typical for 5q- syndrome. We decided to evaluate the roles of
      EKLF and Fli1 in the pathogenesis of this syndrome and of another ribosomopathy,
      Diamond-Blackfan anemia (DBA). Fli1 and EKLF mRNA levels were examined in
      mononuclear blood and bone marrow cells from patients with 5q- syndrome, low-risk
      MDS patients with normal chromosome 5, DBA patients, and healthy controls. In 5q-
      syndrome, high Fli1 mRNA levels in the blood and bone marrow mononuclear cells
      were found. In DBA, Fli1 expression did not differ from the controls. EKLF mRNA
      level was significantly decreased in the blood and bone marrow of 5q- syndrome
      and in all DBA patients. We propose that the elevated Fli1 in 5q- syndrome
      protects megakaryocytic cells from ribosomal stress contrary to erythroid cells
      and contributes to effective though dysplastic megakaryopoiesis.

PMID- 22965554
TI  - A novel malate dehydrogenase from Ceratonia siliqua L. seeds with potential
      biotechnological applications.
AB  - A novel malate dehydrogenase (MDH; EC 3.1.1.1.37), hereafter MDHCs, from
      Ceratonia siliqua seeds, commonly known as Carob tree, was purified by using
      ammonium sulphate precipitation, ion exchange chromatography on SteamLine SP and
      gel-filtration. The molecular mass of the native protein, obtained by analytical
      gel-filtration, was about 65 kDa, whereas, by using SDS-PAGE analysis, with and
      without reducing agent, was 34 kDa. The specific activity of purified MDHCs (0.25
      mg/100 g seeds) was estimated to be 188 U/mg. The optimum activity of the enzyme
      is at pH 8.5, showing a decrease in the presence of Ca(2+), Mg(2+) and NaCl. The
      N-terminal sequence of the first 20 amino acids of MDHCs revealed 95 % identity
      with malate dehydrogenase from Medicago sativa L. Finally, the enzymatic activity
      of MDHCs was preserved even after absorption onto a PVDF membrane. To our
      knowledge, this is the first contribution to the characterization of an enzyme
      from Carob tree sources.

PMID- 22965556
TI  - Primary intraocular large B cell lymphoma with plasmacytic differentiation.

PMID- 22965555
TI  - Purification and biological activities of Abelmoschus esculentus seed lectin.
AB  - The Abelmoschus esculentus (Malvaceae) plant originated in Africa and has spread
      across a number of tropic countries, including northeastern Brazil. The plant has
      been used to treat various disorders, such as cancer, microbial infections,
      hypoglycemia, constipation, urine retention and inflammation. The lectin of A.
      esculentus (AEL) was isolated by precipitation with ammonium sulfate at a
      saturation level of 30/60 and purified by ion exchange chromatography (Sephacel
      DEAE). The electrophoresis (SDS-PAGE) profile of the AEL showed two protein bands
      of apparent molecular mass of approximately 15.0 and 21.0 kDa. The homogenity of
      the protein was confirmed by electrospray mass spectrometry (ESI-MS), which
      revealed the presence of a 10.29-kDa monomer and a 20.58-kDa dimer. The AEL
      exhibits agglutinating activity against rabbit (74.41 UH/mP) and human type ABO
      erythrocytes (21.00 UH/mP). This activity does not require the presence of
      divalent cations and is specifically inhibited by lactose, fructose and mannose.
      The intravenous treatment with 0.01, 0.1 and 1 mg/kg of AEL inhibited the paw
      edema elicited by carrageenan by approximately 15, 22 and 44 %, respectively, but
      not that induced by dextran. In addition, treatment with 0.1, 1 and 10 mg/kg of
      AEL also inhibited the abdominal writhing induced by acetic acid by approximately
      52, 57 and 69 %, respectively. In conclusion, AEL is a new lectin with a
      molecular mass of 20.0 kDa, which is -composed of a 10.291-Da monomer and a
      20.582-kDa dimer, that exhibits anti-inflammatory, antinociceptive and
      hemagglutinating activities. In addition, the lectin hemagglutinating property is
      both metallo-independent and associated with the lectin domain.

PMID- 22965557
TI  - Total synthesis of marine eicosanoid (-)-hybridalactone.
AB  - (-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga
      Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13
      membered macrolactone and epoxide ring systems incorporating seven stereogenic
      centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In
      this paper, we report on the total synthesis of (-)-hybridalactone (1). The
      unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically
      active gamma-butyrolactone 2 in a linear sequence comprising 21 steps with an
      overall yield of 21.9%. A key step in the synthesis of (-)-hybridalactone (1) is
      the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis
      cyclopropane-gamma-lactone derivative. This reaction provided an efficient and
      stereoselective access to cis-cyclopropane-gamma-lactone 12. Further elaboration
      of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig
      olefination and Shiina macrolactonization afforded (-)-hybridalactone.

PMID- 22965558
TI  - A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle
      Biopsy.
AB  - Nemaline rods are the pathologic hallmark of nemaline myopathy, but they have
      also been described as a secondary phenomenon in a variety of other disorders.
      Nemaline rods have not been reported in pyruvate carboxylase deficiency before.
      Here we present a patient with pyruvate carboxylase deficiency and nemaline rods
      detected on muscle biopsy. The nemaline rods may be due to cellular energy
      shortage and altered energy metabolism in pyruvate carboxylase deficiency,
      similar to that in the previously reported patients. The mechanism of nemaline
      rod formation may be associated with the role of pyruvate carboxylase in cellular
      energy pathways.

PMID- 22965559
TI  - Unusual Case of Phenylketonuria With Atypical Brain Magnetic Resonance Imaging
      Findings.
AB  - Phenylketonuria is a treatable inborn error of amino acid metabolism caused by
      deficiency of the enzyme phenylalanine hydroxylase, responsible for converting
      phenylalanine to tyrosine. We report a 10-month-old boy with psychomotor
      regression and infantile spasms. He was diagnosed with classic phenylketonuria
      and West syndrome. Treatment was initiated with phenylalanine-restricted diet and
      vigabatrin. After 5 months of treatment, he persists with developmental delay,
      severe hypotonia, swallowing disorder, and drug-resistant epilepsy. Brain
      magnetic resonance imaging showed the typical abnormalities in supratentorial
      white matter and exceptional infratentorial and basal ganglia compromise.
      Severity of white matter abnormalities and neurologic symptoms correlates with
      blood levels of phenylalanine. Infratentorial changes occur in severe cases.
      Other mechanisms could take part in cases like this with atypical neuroimaging
      abnormalities of the basal ganglia.

PMID- 22965560
TI  - Ten Years' Follow-Up of a Family With Myokymia and Muscle Cramps Without Ataxia.
AB  - We report 10 years' follow-up of the previously described family with a novel
      mutation of the KCNA1 gene. The family consisted of 3 affected boys (first seen
      at ages 3, 11, and 12) and their affected mother and asymptomatic father and
      sister. They clinically presented with diffuse myokymia, muscle cramps, and lower
      limb spasticity without ataxia, but episodic ataxia developed later during
      adolescence and early adulthood. Long-term follow-ups of families with known
      KCNA1 gene mutation are rarely mentioned in the literature. Treatment with
      carbamazepine, 600 to 800 mg daily resulted in cessation of muscle cramps and
      marked improvement of lower leg symptoms. In the youngest child, after 2 years
      carbamazepine had to be changed to oxcarbazepine because of side effects.
      Carbamazepine and oxcarbazepine are both effective in treatment of symptoms
      related to KCNA1 gene mutation. Symptoms will reoccur if treatment is stopped and
      there is variability of symptom severity between family members.

PMID- 22965561
TI  - Novel Mutations in FA2H-Associated Neurodegeneration: An Underrecognized
      Condition?
AB  - Hereditary spastic paraplegias and related genetically heterogeneous disorders
      may be difficult to distinguish clinically. The FA2H gene has been associated
      with autosomal recessive neurodegenerative phenotypes encompassing spastic
      paraplegia with or without dystonia, and demyelinating leukodystrophy. To date,
      few individuals with mutations in the FA2H gene have been described. We report a
      5-year-old girl of mixed Filipino and Vietnamese origin who presented with
      progressive lower limb spasticity and periventricular leukomalacia. The clinical
      diagnosis of FA2H-associated neurodegeneration was confirmed on the basis of 2
      novel mutations in compound heterozygosity in the FA2H gene (p.S70L/p.P323L).
      This family highlights that FA2H-associated disorders may be underrecognized in
      children with neurodegeneration of many different ethnicities. Magnetic resonance
      imaging features play an important role as diagnostic clues in this and other
      hereditary spastic paraplegias. The consideration of this diagnosis is essential
      in providing families with important information on prognosis, as well as
      accurate genetic counseling.

PMID- 22965562
TI  - Basal Ganglia Injury With Extrapyramidal Presentation: A Complication of
      Meningococcal Meningitis.
AB  - Basal ganglia injury, accompanied by extrapyramidal signs, has been described in
      the setting of chronic tuberculous meningitis; however, such injury rarely occurs
      in acute bacterial meningitis and has never been reported with meningococcal
      meningitis. We report the case of a boy who developed tongue bradykinesia and
      dysarthria 1 week following presentation with meningococcal meningitis. Magnetic
      resonance imaging revealed bilateral basal ganglia lesions, suspected to result
      from cytotoxic edema secondary to infection. The patient subsequently developed
      general bradykinesia, choreoathetosis, and ataxia, which had improved but not
      completely subsided by the time of discharge, 8 weeks following initial
      presentation. The purpose of this report is to present basal ganglia injury with
      extrapyramidal signs as a possible complication of meningococcal meningitis.
      Furthermore, we emphasize the importance of suspecting parkinsonian signs as
      early indicators of basal ganglia involvement in the setting of meningitis, which
      may later develop into a full-blown movement disorder.

PMID- 22965563
TI  - Dendritic, axonal, and spinal pathology of the Purkinje cells and the neurons of
      the dentate nucleus after long-term phenytoin administration: a case report.
AB  - Phenytoin is a commonly prescribed anticonvulsant drug; however, there is
      evidence that long-term administration is related to cerebellar ataxia,
      cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia
      cells. The aim of the present study was to detect and describe any possible
      alterations of the Purkinje cells, and neurons of the dentate nucleus, as those
      can be seen with the use of silver impregnation techniques, such as Golgi and
      Nauta method. The study was performed on a 7-year-old boy who was under phenytoin
      treatment for more than 3.5 years and had clinical manifestations of cerebellar
      ataxia. Golgi silver impregnation technique revealed substantial loss of
      dendritic spines and tertiary dendritic branches, both on the Purkinje cells and
      the neurons of the dentate nucleus, whereas the Nauta method demonstrated swollen
      and degenerated axons of Purkinje cells. 

PMID- 22965564
TI  - Cerebellar pathway changes following cerebral hemispherectomy.
AB  - Following unilateral cerebral injury, several patterns of cerebellar metabolism
      have been noted on positron emission tomography (PET); these changes have been
      attributed both to the distant diaschisis as well as to reorganizational changes
      within the cerebellum. We used diffusion tensor magnetic resonance imaging (MRI)
      to study 14 children who had undergone cerebral hemispherectomy because of
      intractable epilepsy and compared them with those from 17 controls. In 10
      children who had preoperative and postoperative scans, a paired comparison was
      performed. Our findings showed significantly higher fractional anisotropy values
      in corticopontocerebellar pathways postoperatively compared to preoperatively.
      When compared to controls, we found a higher rate of age-related fractional
      anisotropy changes of corticopontocerebellar pathways in the postoperative scans.
      Our results indicate reorganizational changes in the contralateral (intact)
      corticopontocerebellar pathway and the cerebellar white matter. These changes
      likely contribute to the far better motor outcomes seen in children compared to
      adults sustaining such cortical injuries. 

PMID- 22965565
TI  - Comparative morphology of porpoise (Cetacea: Phocoenidae) pterygoid sinuses:
      phylogenetic and functional implications.
AB  - High-resolution X-ray computed tomographic scans were used to examine pterygoid
      sinus morphology within extant porpoise species and one delphinid (Tursiops
      truncatus), in order to consider: 1) intraspecific and interspecific variation
      among the studied species; 2) the most parsimonious sequence of character
      acquisition; and 3) the potential functional roles of the preorbital lobes of the
      sinuses in sound reflection. Scans revealed that the pterygoid/palatine regions
      are mediolaterally broader in the earliest diverging phocoenid (Neophocaena
      phocaenoides) and Tursiops truncatus than the dorsoventrally elongated sinuses
      observed in other species. Rostrocaudal lengths of the sphenoidal regions of the
      sinuses in all individuals studied are proportionally similar, indicating
      conservatism in this region across species. The neonate Phocoena phocoena has
      shorter preorbital lobes than adults, but they are still proportionally longer
      than Neophocaena phocaenoides and Phocoena spinipinnis. The preorbital lobes
      broaden mediolaterally to varying degrees across species; in particular,
      Phocoenoides dalli has the largest dorsal and lateral expansion of this region.
      Assuming the highest pulse frequency produced by porpoises is 150 kHz, all
      regions of the preorbital lobes are thick enough to reflect the wavelengths
      produced. In addition, the neonate preorbital lobes are not as elongated as they
      are in adults, and the dorsal third of this region may not reflect sound to the
      same extent. This study reinforces the importance of using nondestructive methods
      to quantify variation in endocranial anatomy and the value of CT data for
      recovering phylogenetically useful information, as well as functional roles
      sinuses play in concert with the soft tissue head anatomy for biosonar.

PMID- 22965567
TI  - Cost-effectiveness of treatment strategies for pancreatic head adenocarcinoma and
      potential opportunities for improvement.
AB  - BACKGROUND: Generally dismal outcomes have led to a nihilistic attitude toward
      treating pancreatic cancer, while fiscal constraints have increased scrutiny of
      treatments costs. Our objective was to compare the cost-effectiveness of various
      treatment strategies for resectable pancreatic head adenocarcinoma, and to
      identify opportunities for improved cost effectiveness. METHODS: A decision model
      compared 6 strategies: no treatment, radiotherapy only, chemotherapy only,
      chemotherapy plus radiotherapy, surgery alone, and surgery plus adjuvant therapy.
      Outcomes and probabilities were identified using the National Cancer Data Base,
      the American Cancer Society National Surgical Quality Improvement Program, and
      the literature. Costs were estimated using Medicare payment. Incremental cost
      effectiveness ratios (ICERs) were calculated, and sensitivity analyses were
      performed by varying potentially modifiable parameters of the model. Survival was
      reported in quality-adjusted life-months (QALMs). RESULTS: Surgery plus adjuvant
      therapy, chemotherapy alone, and no treatment were the only viable strategies in
      terms of cost effectiveness. Surgery plus adjuvant therapy versus no treatment
      demonstrated an incremental cost-effectiveness ratio (ICER) of $7,663/QALM.
      Theoretically increasing survival in node-negative, margin-negative patients from
      14 to 22 QALMs produced the largest reduction in the ICER for surgery plus
      adjuvant therapy compared to no treatment ($6,386/QALM), whereas reducing the
      perioperative mortality from 3 to 1 % had only a marginal effect. The ICER was
      significantly lower for high-performing centers ($5,991/QALM) than for low
      performing centers ($9,144/QALM). CONCLUSIONS: Surgery plus adjuvant therapy for
      resectable pancreatic head adenocarcinoma extends survival, but at considerable
      expense. Significant cost reductions could be realized by improving treatment
      outcomes to levels of high-performing centers and development of increasingly
      effective adjuvant therapies.

PMID- 22965566
TI  - Chromatin-linked determinants of zygotic genome activation.
AB  - The merging of the maternal and paternal genomes into a single pronucleus after
      fertilization is accompanied by a remarkable reconfiguration of chromatin in the
      newly formed zygote. The first stages of embryonic chromatin remodeling take
      place in the absence of ongoing transcription, during a species-specific
      developmental time-frame. Once post-fertilization chromatin states are organized,
      zygotic genome activation (ZGA) is initiated, and embryonic transcripts gradually
      take control of development. We review here transitions in chromatin
      modifications associated with the onset of ZGA, and the role of transcription
      factors and DNA motifs in the regulation of ZGA. We propose a model of sequential
      chromatin remodeling events preceding ZGA, leading to the onset of embryonic
      transcription.

PMID- 22965568
TI  - Illness-related distress in women with clinically localized cutaneous melanoma.
AB  - BACKGROUND: Women may experience distress or changes in their quality of life
      following treatment for early-stage melanoma. In order to plan future
      interventions and identify areas of primary concern, we conducted a cross
      sectional survey to describe the experiences of women treated for clinically
      localized melanoma. METHODS: We examined quality of life, levels of distress,
      appearance perceptions, body image, fear of recurrence, and reproductive concerns
      in 100 patients (age 21-90 years, M = 54.34 years). Most (61 %) had melanoma of
      the extremity, with a median depth of 1.1 mm (range, 0-10.5 mm). RESULTS:
      Significant depressive symptomatology occurred in 10 % of patients, and 12 %
      reported a clinically established high level of intrusive thoughts related to
      melanoma. Quality-of-life scores indicated more disruption on psychological,
      compared with social and physical functioning. Also, 64 % of women rated their
      appearance as worse post-treatment; 23 % were unsatisfied with the appearance of
      the surgical site. Recurrence concerns indicated significant worry about health
      and death. Most patients (>85 %) were not concerned about fertility, but 52 %
      worried that future children would have an increased risk of cancer. CONCLUSIONS:
      Some women treated for clinically localized melanoma reported high levels of
      distress associated with their altered body image and fear of recurrence.
      Improvements in patient education prior to surgical intervention may reduce the
      distress associated with the diagnosis and treatment of melanoma.

PMID- 22965569
TI  - Desmoid tumor: analysis of prognostic factors and outcomes in a surgical series.
AB  - BACKGROUND: Desmoid tumors are rare and exhibit a highly unpredictable natural
      history. We sought to analyze prognostic factors associated with recurrence in a
      large single-institution study of patients with desmoid tumors. METHODS: We
      performed a retrospective review of 177 patients with desmoid tumor who underwent
      macroscopically complete surgical resection, with or without the addition of
      radiotherapy (RT) or systemic therapy, from 1970 to 2009. We examined patterns of
      presentation, all known risk factors for recurrence, and their association with
      recurrence-free survival (RFS). RESULTS: Twenty-two patients (12 %) had intra
      abdominal desmoid tumors, and 155 (88 %) had extra-abdominal tumors. Patterns of
      presentation included primary (n = 133, 75 %) and locally recurrent (n = 44, 25
      %) disease. Treatment was surgery alone in 125 patients (71 %), surgery and RT in
      36 (20 %), and surgery and systemic therapy with or without RT in 20 (11 %).
      Median follow-up was 40 months. Overall, the local relapse rate was 29 %, and 10
      year RFS was 60 %. R0 resection status was the only predictor of freedom from
      local recurrence on multivariate analysis (odds ratio 0.32; 95 % confidence
      interval 0.15-0.66; P = 0.002). The selective use of adjuvant RT appeared to
      improve local control in patients with positive margins. CONCLUSIONS: For
      patients with desmoid tumors undergoing surgery, wide excision with negative
      margins should be the goal, but not at the expense of function, as fewer than
      half of patients with positive margins will experience recurrence.

PMID- 22965570
TI  - Inflammatory markers are associated with outcome in patients with unresectable
      hepatocellular carcinoma undergoing transarterial chemoembolization.
AB  - BACKGROUND: The serum neutrophil-lymphocyte ratio (NLR) is associated with
      outcomes in several solid organ cancers, including hepatocellular carcinoma
      (HCC). METHODS: We reviewed our experience in patients with HCC who underwent
      transarterial chemoembolization (TACE) as the initial treatment. Serum complete
      blood counts were used to calculate the NLR before and after TACE. The Kaplan
      Meier method was used to determine survival and significant differences between
      groups by the log-rank test. RESULTS: There were 103 patients identified who
      underwent TACE for HCC. The median age was 60.5 years. Median overall survival
      was 12.6 (95% confidence interval 8.3-17) months. Median survival in patients
      with a high preprocedural NLR was 4.2 months compared to 15 months in those with
      a normal NLR (p = 0.021). In those whose NLR either rose 1 month after treatment
      or remained elevated, survival was worse compared to those who normalized or
      remained normal (18.6 vs. 10.6 months, p = 0.026). The same was true at 6 months
      (21.3 vs. 9.5 months, p = 0.002). An unresponsive NLR was associated with very
      poor outcome (median survival 3.7 months). Multivariate analysis of
      clinicopathologic factors showed that presence of extrahepatic disease and high
      NLR were independent factors associated with worse survival. CONCLUSIONS: Our
      study demonstrates that periprocedural trends of serum NLR are associated with
      outcome in unresectable HCC undergoing TACE. Serum NLR is easy to calculate from
      a routine complete blood count with differential. Along with liver function,
      serum NLR may be helpful to clinicians in providing prognostic information and
      monitoring response to therapy.

PMID- 22965571
TI  - Predicting nipple-areolar involvement using preoperative breast MRI and primary
      tumor characteristics.
AB  - BACKGROUND: Preoperative assessment of the nipple-areolar complex (NAC) is
      invaluable when considering nipple-sparing mastectomy. Our hypothesis is that
      breast magnetic resonance imaging (MRI) may predict involvement of the NAC with
      tumor. METHODS: Clinical, histopathologic, and imaging data were compiled for
      patients who underwent preoperative breast MRI followed by mastectomy or nipple
      sparing mastectomy for malignancy between 2006 and 2009. Blinded rereview of all
      MRI studies was performed by a breast MRI imager and compared to initial MRI
      findings. Multivariate analysis identified variables predicting NAC involvement
      with tumor. RESULTS: Of 77 breasts, 18 (23 %) had tumor involving or within 1 cm
      of the NAC. The sensitivity of detecting histopathologically confirmed NAC
      involvement was 61 % with history and/or physical examination, and 56 % with MRI.
      Univariate analysis identified the following variables as significant for NAC
      involvement: large tumors near the nipple on preoperative MRI, node-positive
      disease, invasive lobular carcinoma, advanced histopathologic T stage, and
      neoadjuvant chemotherapy. On multivariate analysis, only tumor size >2 cm and
      distance from tumor edge to the NAC <2 cm on MRI maintained significance. Pearson
      correlation coefficient for MRI size compared to histopathologic size was 0.53 (P
      < 0.0001). CONCLUSIONS: MRI is not superior to thorough clinical evaluation for
      predicting tumor in or near the NAC. However, MRI-measured tumor size and
      distance from the NAC are correlated with increased risk of NAC involvement. The
      combination of preoperative history and physical examination, tumor
      characteristics, and breast MRI can aid the surgeon in predicting a tumor
      involved nipple more than any single modality alone.

PMID- 22965572
TI  - Palliative venting gastrostomy in patients with malignant bowel obstruction and
      ascites.
AB  - BACKGROUND: Fluoroscopic-guided placement of a percutaneous decompression
      gastrostomy tube (PDGT) is used to palliate patients with malignant bowel
      obstruction (MBO). We report our clinical experience in cases of MBO and ascites
      that were known to be technically difficult and at increased risk for
      complications after PDGT placement. METHODS: Between October 2005 and April 2010,
      a total of 89 consecutive oncology patients with MBO and ascites underwent at
      least one attempt at PDGT placement. We retrospectively reviewed the electronic
      medical record to collect demographic details, procedure information, and
      morbidity and mortality data. Kaplan-Meier curves were used to calculate median
      survival after PDGT. RESULTS: Ninety-three new gastrostomy encounters occurred in
      89 patients. The primary and secondary technical success rates were 72 % (67 of
      93) and 77.4 % (72 of 93), respectively. Inadequate gastric distention was the
      reason for failure in 84.6 % (22 of 26) of the cases in which the initial PDGT
      attempt was unsuccessful. For ascites management, 13 patients underwent
      paracentesis and 78 patients underwent placement of an intraperitoneal catheter.
      The overall complication rate in successful placements was 13.9 %, with a major
      complication rate of 9.7 %. After PDGT, the median overall survival rate was 28.5
      days (95 % confidence interval 20-42). CONCLUSIONS: PDGT is feasible in the
      majority of patients with MBO and ascites, although there is an inherent risk of
      major complications. An intraperitoneal catheter can be used to manage ascites to
      facilitate PDGT.

PMID- 22965573
TI  - Gastrointestinal stromal tumor of the rectum: results of surgical and
      multimodality therapy in the era of imatinib.
AB  - BACKGROUND: The rectum is a rare site of gastrointestinal stromal tumor (GIST),
      and factors determining long-term outcome remain unclear. In a population study,
      we assessed the outcome of rectal GIST patients treated at two referral centers.
      METHODS: A total of 39 patients diagnosed with rectal GIST between January 2002
      and December 2010 were identified in prospective databases. Tumor and patient
      characteristics, treatment details, and outcome were evaluated. Median follow-up
      was 41 (3-110) months. RESULTS: A male predominance was noticed (M/F = 29/10).
      Median age was 53 years (range, 32-80 years). The cohort included, of 39
      patients, 12 low-risk, 26 high-risk, and 1 with M1 disease. Of 38 patients with
      nonmetastatic disease, 36 underwent surgery as transabdominal (15 of 36) or local
      (21 of 36) resection. There were 21 patients who received preoperative and/or
      postoperative imatinib treatment. Patients with preoperative imatinib (16 of 36)
      had a significantly higher rate of R0 resections (p = .02). Five patients
      developed local recurrences. All of them had undergone local tumor excision with
      positive margins and without perioperative imatinib. Also, five patients suffered
      from distant metastases. All belonged to the high-risk group and underwent tumor
      surgery (3 R0, 2 R1) without receiving perioperative imatinib. A total of three
      patients died of disease. Perioperative imatinib was associated with improved
      local disease-free, disease-free, and overall survival (p < .01, p < .01, and p =
      .03, respectively). Local disease-free survival was significantly improved by
      negative resection margins (p < .01). CONCLUSIONS: Complete resection is
      recommended to achieve local disease control. Preoperative imatinib was
      associated with improved surgical margins. Perioperative imatinib was associated
      with improved local disease-free, disease-free, and overall survival.

PMID- 22965574
TI  - Single HCC in cirrhotic patients: liver resection or liver transplantation? Long
      term outcome according to an intention-to-treat basis.
AB  - BACKGROUND: Compensated cirrhotic patients with single hepatocellular carcinoma
      (HCC) <=5 cm may benefit from both liver resection (LR) and liver transplantation
      (LT); however, the better 10-year actuarial survival of the two treatments
      remains unclear. We aimed to assess the long-term outcome of cirrhotic patients
      with single HCC <=5 cm treated either with LR or LT on an intention-to-treat
      basis. METHODS: A total of 217 cirrhotic patients with single HCC <=5 cm were
      evaluated at our department: 95 were treated with LR (LR group), and 122 were
      included on the waiting list for LT (LT group). Patients in the LR group were
      divided into very early HCC (tumor size <=2 cm) and early HCC (tumor size >2 cm).
      Median follow-up was 5.3 (range 0.1-18) years. RESULTS: Tumor recurrence was 72 %
      in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year
      cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18,
      and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the
      LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were
      included on the waiting list for salvage transplantation (very early HCC group)
      versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC
      recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p =
      0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial
      survival between the very early HCC group and the LT group (95, 55, and 50 % vs.
      82, 62, and 50 %). CONCLUSIONS: LR should be the treatment of choice for
      cirrhotic patients with very early HCC.

PMID- 22965575
TI  - Phase II trial of adjuvant chemotherapy with S-1 for colorectal liver metastasis.
AB  - BACKGROUND: This phase II trial was designed to evaluate the safety and efficacy
      of adjuvant chemotherapy with S-1 in patients with curatively resected liver
      metastasis from colorectal cancer. Results of an interim analysis of safety and
      short-term outcomes are reported. METHODS: Patients who underwent curative
      resection of liver metastasis from colorectal cancer received S-1 monotherapy (on
      days 1-28, followed by 14 days' rest, 8 cycles) as adjuvant chemotherapy.
      RESULTS: Among 62 patients enrolled between October 2008 and August 2010, a total
      of 60 patients were eligible for analysis. The most frequent grade 3 or higher
      hematologic toxicity involved neutropenia in three patients (5.0 %).
      Nonhematologic toxicities of grade 3 or higher were fatigue in 6.7 % of patients.
      Grade 4 enteritis occurred in one patient, but resolved promptly after withdrawal
      of S-1 therapy. The completion rate of the eight scheduled cycles of chemotherapy
      was 58.3 %. The most common reasons for withdrawal of treatment was the detection
      of early relapse in 16 patients (64 %). When the 16 patients who had recurrence
      during adjuvant treatment were excluded from analysis, 79.5 % of the remaining 44
      patients completed the scheduled treatment. Early recurrence within 1 year after
      curative liver resection occurred in 21 patients (35 %). The most common site was
      the remnant liver in 14 patients. CONCLUSIONS: Orally administered S-1 after
      curative liver resection has an acceptable toxicity profile and a high rate of
      completion of the therapy. S-1 can be safely used and might be a viable treatment
      option in an adjuvant setting.

PMID- 22965577
TI  - Partial molecular characterization of different proviral strains of bovine
      leukemia virus.
AB  - Bovine leukemia virus (BLV)-infected cattle were classified by their proviral
      load into low and high proviral load profiles (LPL and HPL, respectively). Blood
      from these animals was used to infect sheep to obtain multiple identical copies
      of integrated provirus. An env fragment of BLV was amplified from all infected
      sheep and sequenced. The sequences that were obtained were compared to already
      published BLV genome sequence, resulting in three clusters. Mutations could not
      be attributed to the passage of provirus from cattle to sheep and subsequent
      amplification and sequencing. The description of two different proviral load
      profiles, the association of the BoLA-DRB3.2 0902 allele with the LPL profile,
      the availability of complete BLV sequences, and the comparison of a variable
      region of the env gene from carefully characterized cattle are still not enough
      to explain the presence of animals in every herd that are resistant to BLV
      dissemination.

PMID- 22965578
TI  - Phenotypic and molecular characteristics of plaque-purified MX10 virus, an
      Oriental-Australian genotype of Sindbis virus from Yunnan, China.
AB  - A previous investigation showed that MX10 virus, recently isolated in China,
      belongs to the Oriental-Australian (O/A) genotype of Sindbis virus (SINV) (Wang
      Jinglin, 2011, ATMH). Similar to the MRE16 isolate, the prototype O/A genotype of
      SINV, two derivate viruses with obviously different plaque morphologies were
      derived from MX10 virus, which were accordingly denoted as MX10-LP and MX10-SP.
      MX10-LP virus exhibited higher neurovirulence in neonatal mice than MX10-SP
      virus. Analysis of the complete genome revealed seven nucleotide differences
      between MX10-LP and MX10-SP. Compared with MRE16 virus, MRE16SP virus has a
      deletion of 30 aa in the E2 gene (200-229), which has been shown to be the
      molecular basis for the different plaque morphology. However, the MX10-SP virus
      did not have the 30-amino-acid deletion in the E2 gene. These results demonstrate
      that the molecular basis for the different plaque morphology of MX10 virus, the
      first strain of the O/A genotype of SINV isolated from China, is different from
      that of the prototype MRE16 virus.

PMID- 22965579
TI  - Human papillomavirus type 58 L1 virus-like particles purified by two-step
      chromatography elicit high levels of long-lasting neutralizing antibodies.
AB  - Human papillomavirus (HPV) type 58 is a high-risk type of HPV frequently detected
      in cervical cancers, especially in Eastern Asia. There are still no commercially
      available vaccines against HPV 58 infection. High levels of long-lasting
      neutralizing antibodies are crucial for long-term protection against HPV
      infection. Here, we have developed a two-step chromatography strategy and have
      purified highly pure HPV L1 proteins, which form more homogenous and uniform VLPs
      than those purified by CsCl ultracentrifugation. Low-dosage immunization with HPV
      58 L1 VLPs alone or co-administrated with HPV 16 and HPV 18 L1 VLPs is sufficient
      to induce high levels of long-lasting neutralizing antibodies in mice. Our
      results suggest that the highly immunogenic HPV 58 L1 VLPs are a good candidate
      for use in developing effective vaccines against HPV 58 infection.

PMID- 22965580
TI  - Characterization of a new Anulavirus isolated from Amazon lily plants.
AB  - A quasi-spherical virus was isolated from a cultivated Amazon lily plant
      (Eucharis grandiflora) that could be mechanically transmitted to healthy E.
      grandiflora plants, subsequently producing mild mosaic or mottle symptoms on the
      leaves. The purified virus consisted of three quasi-spherical particles about 20
      nm wide and 70, 40 and 30 nm in length, containing three segmented genomes of
      3,169, 2,507 and 2,530 nucleotides, respectively. Sequence analysis showed that
      the newly isolated virus is related to pelargonium zonate spot virus, a member of
      the genus Anulavirus. We propose that the virus should be designated as Amazon
      lily mild mottle virus (ALiMMV).

PMID- 22965581
TI  - Robust and aligned carbon nanotube/titania core/shell films for flexible TCO-free
      photoelectrodes.
AB  - Carbon nanotube (CNT)/semiconducting oxide hybrids are an ideal architecture for
      light-harvesting devices, in which the CNTs are expected to not only act as a
      scaffold but also provide fast transport paths for photogenerated charges in the
      oxide. However, the current potential of CNTs for charge transport is largely
      suppressed due to the nanotubes not being interconnected but isolated by the low
      conductive oxide coatings. Herein, a flexible and conductive CNT/TiO(2) 
      core/shell heterostructure film is reported, with aligned and interconnected CNTs
      wrapped in a continuous TiO(2)  coating. Without using additional transparent
      conducting oxide (TCO) substrates, this unique feature of the film boosts the
      incident photon-to-electron conversion efficiency to 32%, outperforming TiO(2) 
      nanoparticle electrodes fabricated on TCO substrates. Moreover, the film shows
      high structural stability and can generate a stable photocurrent even after being
      bent hundreds of times.

PMID- 22965582
TI  - Round cell liposarcoma arising in the left foot: MRI and PET findings.
AB  - Liposarcomas are one of the most common soft-tissue sarcomas and commonly arise
      in the deep soft tissues of the extremities and retroperitoneum; however, the
      occurrence of liposarcomas in the foot or ankle is exceedingly rare. In this
      article, we present a 52-year-old man with round cell liposarcoma arising in the
      left foot. This tumor presented unusual manifestations of secondary osseous
      involvement in the metatarsal and tarsal bones of the left foot and solitary
      lymph node metastasis at the para-aortic region. Magnetic resonance imaging (MRI)
      and [(18)F]-fluoro-deoxy-glucose positron emission tomography computed tomography
      (FDG PET-CT) evaluation was considered to be useful for tumor grading and staging
      in this case.

PMID- 22965583
TI  - Nuclear and cellular alignment of primary corneal epithelial cells on topography.
AB  - The basement membrane of the corneal epithelium presents biophysical cues in the
      form of topography and compliance that can modulate cytoskeletal dynamics, which,
      in turn, can result in altering cellular and nuclear morphology and alignment. In
      this study, the effect of topographic patterns of alternating ridges and grooves
      on nuclear and cellular shape and alignment was determined. Primary corneal
      epithelial cells were cultured on either planar or topographically patterned (400
      4000 nm pitch) substrates. Alignment of individual cell body was correlated with
      respective nucleus for the analysis of orientation and elongation. A biphasic
      response in alignment was observed. Cell bodies preferentially aligned
      perpendicular to the 800 nm pitch; and with increasing pitch, cells increasingly
      aligned parallel to the substratum. Nuclear orientation largely followed this
      trend with the exception of those on 400 nm. On this biomimetic size scale, some
      nuclei oriented perpendicular to the topography while their cytoskeleton elements
      aligned parallel. Both nuclei and cell bodies were elongated on topography
      compared to those on flat surfaces. Our data demonstrate that nuclear orientation
      and shape are differentially altered by topographic features that are not
      mandated by alignment of the cell body. This novel finding suggests that nuanced
      differences in alignment of the nucleus versus the cell body exist and that these
      differences could have consequences on gene and protein regulation that
      ultimately regulate cell behaviors. A full understanding of these mechanisms
      could disclose novel pathways that would better inform evolving strategies in
      cell, stem cell, and tissue engineering as well as the design and fabrication of
      improved prosthetic devices.

PMID- 22965584
TI  - Ototopical neomycin exposure in children with nonintact tympanic membranes.
AB  - OBJECTIVES/HYPOTHESIS: Although contraindicated, neomycin otic preparations may
      be administered to children with nonintact tympanic membranes (TMs), such as
      tympanostomy tubes or TM perforations. The goal of this study was to assess the
      magnitude of neomycin exposure in children with nonintact TMs. STUDY DESIGN:
      Retrospective drug utilization study. METHODS: Medicaid claims data (years 1999
      2006) from 28 states for children aged 0 to 18 years were analyzed to identify
      new cases of tube placement or TM perforation. Cases were followed for 12 months
      to determine neomycin otic utilization. RESULTS: Of the 300,470 children with
      nonintact TMs, neomycin otic preparations were prescribed in 43,815 (15%).
      Nontoxic agents (ofloxacin or ciprofloxacin) were used in 48%. In 19%, neomycin
      preparations were prescribed at the day of initial nonintact TM diagnosis, 52%
      and 71% within the first 3 or 6 months, respectively. Neomycin otic utilization
      decreased from 27% in cases diagnosed in 1999 to 7% in 2005 (P < .0001).
      CONCLUSIONS: Many children with nonintact TMs receive exposure to agents with
      potential ototoxicity, despite the availability of safer alternatives. Further
      study is necessary to determine why neomycin otic preparations continue to be
      prescribed in the presence of nonintact TMs and if such exposure is associated
      with ototoxicity.

PMID- 22965586
TI  - Distribution of damage to the entire retinal ganglion cell pathway: quantified
      using spectral-domain optical coherence tomography analysis in patients with
      glaucoma.
AB  - OBJECTIVES To test the hypothesis that the amount and distribution of
      glaucomatous damage along the entire retinal ganglion cell-axonal complex (RGC
      AC) can be quantified and to map the RGC-AC connectivity in early glaucoma using
      automated image analysis of standard spectral-domain optical coherence
      tomography. METHODS Spectral-domain optical coherence tomography volumes were
      obtained from 116 eyes in 58 consecutive patients with glaucoma or suspected
      glaucoma. Layer and optic nerve head (ONH) analysis was performed; the mean
      regional retinal ganglion cell layer thickness (68 regions), nerve fiber layer
      (NFL) thickness (120 regions), and ONH rim area (12 wedge-shaped regions) were
      determined. Maps of RGC-AC connectivity were created using maximum correlation
      between regions' ganglion cell layer thickness, NFL thickness, and ONH rim area;
      for retinal nerve fiber bundle regions, the maximum "thickness correlation paths"
      were determined. RESULTS The mean (SD) NFL thickness and ganglion cell layer
      thickness across all macular regions were 22.5 (7.5) MUm and 33.9 (8.4) MUm,
      respectively. The mean (SD) rim area across all ONH wedge regions was 0.038
      (0.004) mm2. Connectivity maps were obtained successfully and showed typical
      nerve fiber bundle connectivity of the RGC-AC cell body segment to the initial
      NFL axonal segment, of the initial to the final RGC-AC NFL axonal segments, of
      the final RGC-AC NFL axonal to the ONH axonal segment, and of the RGC-AC cell
      body segment to the ONH axonal segment. CONCLUSIONS In early glaucoma, the amount
      and distribution of glaucomatous damage along the entire RGC-AC can be quantified
      and mapped using automated image analysis of standard spectral-domain optical
      coherence tomography. Our findings should contribute to better detection and
      improved management of glaucoma.

PMID- 22965587
TI  - Massive submacular fibrosis after ocular blunt injury.

PMID- 22965588
TI  - Angiofibrotic response to vascular endothelial growth factor inhibition in
      diabetic retinal detachment: report no. 1.
AB  - OBJECTIVES To assess the effect of bevacizumab injection on connective tissue
      growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular
      fluids of patients with diabetic traction retinal detachment, and to determine
      whether intraoperative and postoperative complications are decreased in eyes
      given adjunctive preoperative bevacizumab injection. METHODS Twenty eyes of 19
      patients were randomized to receive intravitreal bevacizumab or sham injection 3
      to 7 days before vitrectomy for severe proliferative diabetic retinopathy. We
      collected aqueous samples before injection and at the time of vitrectomy and
      extracted undiluted vitreous samples. RESULTS Five eyes had decreased
      vascularization of membranes from preinjection to the time of vitrectomy (all in
      the bevacizumab treatment arm). Median visual acuities were 20/400 in control
      eyes at baseline and postoperative month 3 (POM3) and 8/200 in the bevacizumab
      treated group at baseline and 20/100 at POM3 (P= .30 between control and
      bevacizumab-treated groups at POM3). All retinas were attached at POM3. Vitreous
      levels of VEGF were significantly lower in the bevacizumab group than in the
      control group (P= .03). Vitreous levels of CTGF were slightly lower in the
      bevacizumab group compared with the control group, but this difference was not
      statistically significant (P= .38). Levels of CTGF in the aqueous were strongly
      correlated with CTGF levels in the vitreous of controls (Spearman correlation
      coefficient, 0.95 [P< .001]). CONCLUSIONS Intravitreal bevacizumab injection
      reduces vitreous levels of VEGF and produces a clinically observable alteration
      in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not
      significantly affected within the week after VEGF inhibition. Retinal
      reattachment rates and visual acuity are not significantly altered by
      preoperative intravitreal bevacizumab injection at POM3. TRIAL REGISTRATION
      clinicaltrials.gov Identifier: NCT01270542.

PMID- 22965590
TI  - Long-term effects of ranibizumab on diabetic retinopathy severity and
      progression.
AB  - OBJECTIVE: To evaluate effects of intravitreal ranibizumab on diabetic
      retinopathy (DR) severity over time in 2 phase 3 clinical trials (RIDE,
      NCT00473382; RISE, NCT00473330) of ranibizumab for diabetic macular edema.
      METHODS: Participants with diabetic macular edema (n=759) were randomized to
      monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab intravitreal injections.
      Macular laser was available per protocol-specified criteria. Fundus photographs,
      taken at baseline and periodically, were graded by a central reading center;
      clinical examinations were performed monthly. The main outcome measures of this
      report are secondary/exploratory analyses including a 2-step or more and 3-step
      or more change on the Early Treatment Diabetic Retinopathy Study severity scale
      in the study eye and a composite DR progression outcome including photographic
      changes plus clinically important events such as occurrence of vitreous
      hemorrhage or need for panretinal laser. RESULTS: At 2 years, the percentage of
      participants with DR progression (worsening by >= 2 or >= 3 steps) was
      significantly reduced in ranibizumab-treated eyes compared with sham-treated
      eyes, and DR regression (improving by >= 2 or >= 3 steps) was significantly more
      likely. The cumulative probability of clinical progression of DR as measured by
      the composite outcome at 2 years was 33.8% of sham-treated eyes compared with
      11.2% to 11.5% of ranibizumab-treated eyes. CONCLUSIONS: Intravitreal ranibizumab
      reduced the risk of DR progression in eyes with diabetic macular edema, and many
      ranibizumab-treated eyes experienced improvement in DR severity. Because these
      results are exploratory, the use of intravitreal ranibizumab specifically to
      reduce DR progression or cause DR regression requires further study.

PMID- 22965591
TI  - Factors associated with changes in visual acuity and central subfield thickness
      at 1 year after treatment for diabetic macular edema with ranibizumab.
AB  - OBJECTIVE: To identify factors that predict the success or failure of treatment
      with intravitreal ranibizumab for patients with diabetic macular edema. METHODS:
      A total of 37 baseline demographic, systemic, ocular, optical coherence
      tomographic, and fundus photographic variables were assessed for association with
      change in visual acuity or central subfield thickness between baseline and 1 year
      in 361 eyes that were randomly assigned to intravitreal ranibizumab with prompt
      or deferred laser treatment within a trial of ranibizumab, triamcinolone
      acetonide, and laser treatment for center-involved diabetic macular edema. A
      categorical variable describing follow-up anatomic responses to therapy was added
      to the visual acuity outcome model. RESULTS: After adjusting for baseline visual
      acuity, a larger visual acuity treatment benefit was associated with younger age
      (P< .001), less severe diabetic retinopathy on clinical examination (P= .003),
      and absence of surface wrinkling retinopathy (P< .001). The reduction in central
      subfield thickness during the first treatment year also predicted better visual
      acuity outcomes (P< .001). After adjusting for baseline central subfield
      thickness, the presence of hard exudates was associated with more favorable
      improvement on optical coherence tomographic scan (P= .004). Because only 11 eyes
      experienced vision loss and 6 eyes experienced an increase in central subfield
      thickness, factors for poor outcomes could not be evaluated. CONCLUSIONS: A
      review of baseline factors and anatomic responses during the first year of
      ranibizumab therapy for association with visual acuity outcome did not identify
      any features that would preclude ranibizumab treatment. However, baseline central
      subfield thickness is the strongest predictor of anatomic outcome, and reduction
      in central subfield thickness during the first treatment year is associated with
      better visual acuity outcomes.

PMID- 22965592
TI  - The effectiveness of low-vision rehabilitation in 2 cohorts derived from the
      veterans affairs Low-Vision Intervention Trial.
AB  - OBJECTIVE: To evaluate the effectiveness of low-vision rehabilitation in 2
      cohorts derived from the Veterans Affairs Low-Vision Intervention Trial. METHODS:
      In a prospective study, we observed 44 participants randomly assigned to
      outpatient low-vision rehabilitation who did not receive additional treatment
      after the trial ended at 4-month follow-up and 56 participants randomly assigned
      to the waiting-list control group and thereafter to standard therapy. The outcome
      measures included visual ability domains (reading, mobility, visual information
      processing, and visual motor skills) and overall visual ability estimated from
      difficulty ratings using the 48-item Veterans Affairs Low-Vision Visual
      Functioning Questionnaire. Mean visual ability scores for the treatment and
      control groups were compared at baseline, 4 months, and 1 year. A mixed-effects
      model was used to test treatment effects between groups over time. Differences in
      visual ability mean scores from baseline to 1 year were compared between the 2
      groups. Within-group changes in visual ability were compared from baseline to 1
      year, from baseline to 4 months, and from 4 months to 1 year. RESULTS: At
      baseline, there were no significant differences in mean visual ability scores
      between groups. From baseline to 4 months, the treatment effects for all visual
      ability domains and overall visual ability increased to a maximum in the
      treatment group (P< .001), whereas the mean scores (except visual motor skills)
      decreased in the control group (P< .01). From 4 months to 1 year, the differences
      became smaller. There was a loss of visual ability in reading and visual
      information processing (but not in visual motor skills, mobility, or overall
      visual ability) in the treatment group and a gain in all visual ability measures
      in the control group. Interactions of treatment and follow-up time in the mixed
      models showed the trend of treatment effects significantly changed over time from
      baseline to 1 year (P< .001) for all visual ability domains and overall visual
      ability. Both groups demonstrated improvement in visual ability from baseline to
      1 year (P< .001) (except for mobility in the control group). Overall visual
      ability (but not other visual ability domains) improved more in the treatment
      group than in the control group (P= .01). CONCLUSIONS: Visual ability improved
      significantly in both groups from baseline to 1 year. The Low-Vision Intervention
      Trial treatment effect is robust and well maintained for patients with macular
      diseases.

PMID- 22965593
TI  - Effect of the Y402H variant in the complement factor H gene on the incidence and
      progression of age-related macular degeneration: results from multistate models
      applied to the Beaver Dam Eye Study.
AB  - OBJECTIVES: To investigate the effect of age, sex, and the Y402H variant in the
      complement factor H (CFH) gene on the incidence, progression, and regression of
      age-related macular degeneration (AMD) as well as the effect of these factors and
      AMD on mortality, using multistate models. METHODS: Analyses included 4379
      persons aged 43 to 84 years at the time of the census. The status of AMD on a 5
      level severity scale was graded from retinal photographs taken at up to 5 study
      visits between 1988 and 2010. Multistate models in continuous time were used to
      model the effects of age, sex, and CFH genotype on the incidence, progression,
      and regression of AMD and mortality. RESULTS: The CFH Y402H genotype CC was
      associated, relative to genotype TT (reported as hazard ratio; 95% CI), with
      increased incidence of AMD (no to minimally severe early AMD, 1.98; 1.57-2.49),
      progression of AMD (minimally severe early to moderately severe early AMD, 1.73;
      1.29-2.33; moderately severe early to severe early AMD, 1.30; 0.86-1.94; and
      severe early to late AMD, 1.72; 1.01-2.91) but not with regression of AMD or
      mortality. Late AMD was associated with increased mortality (1.37; 1.15-1.62)
      relative to no AMD, but earlier stages of AMD were not. CONCLUSIONS: Using the
      multistate models, we show that the Y402H risk variant is associated with
      lifetime incidence of early AMD and progression of early to late AMD and that
      late AMD is associated with mortality risk.

PMID- 22965594
TI  - Angle closure in the Namil study in central South Korea.
AB  - OBJECTIVE: To assess the prevalence and associated risk factors of angle closure
      in a defined population as part of the Namil Study. METHODS: In this cross
      sectional epidemiologic study for residents aged 40 years or older in Namil-myon,
      a rural area in central South Korea, the examination included slitlamp
      biomicroscopy, applanation tonometry, gonioscopy, autorefraction, fundus
      photography, corneal thickness measurement, visual field test with frequency
      doubling technology, and anterior chamber depth (ACD) and axial length (AL)
      measurements with partial coherence interferometry. Standard automated field test
      and optical coherence tomography or scanning laser polarimetry were performed to
      confirm the glaucomatous visual field/optic disc damage. Angle closure included
      primary angle-closure suspect (PACS), primary angle closure (PAC), and primary
      angle-closure glaucoma (PACG). Definitions of PACS, PAC, and PACG were based on
      the recommendations from the International Society for Geographical
      &Epidemiological Ophthalmology. RESULTS: Among the 1426 individuals enrolled for
      the assessment, with exclusion of cataract surgery, the prevalence rates of PACS,
      PAC, PACG, and overall angle closure in at least 1 eye were 2.0% (95% CI, 1.3%
      2.8%), 0.5% (95% CI, 0.1%-0.9%), 0.7% (95% CI, 0.3%-1.1%), and 3.2% (95% CI, 2.3%
      4.2%), respectively. Multivariate analysis found that older age (odds ratio [OR],
      1.8797; 95% CI, 1.4624-2.4162), shallower ACD (OR, 0.9982; 95% CI, 0.9977
      0.9987), and shorter AL (OR 0.9978; 95% CI, 0.9969-0.9988) (P < .001 for each)
      were significantly associated with angle closure. CONCLUSIONS: The overall
      prevalence of angle closure was 3.2% in the present study. On the basis of these
      findings, increasing age, shallower ACD, and shorter AL appear to be associated
      with angle closure. TRIAL REGISTRATION clinicaltrials.gov Identifier:
      NCT00727168.

PMID- 22965589
TI  - Retinopathy and chronic kidney disease in the Chronic Renal Insufficiency Cohort
      (CRIC) study.
AB  - OBJECTIVE: To investigate the association between retinopathy and chronic kidney
      disease. METHODS: In this observational, cross-sectional study, 2605 patients of
      the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of
      chronic kidney disease, were offered participation. Nonmydriatic fundus
      photographs of the disc and macula in both eyes were obtained in 1936 of these
      subjects. The photographs were reviewed in a masked fashion at a central
      photograph reading center using standard protocols. Presence and severity of
      retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were
      assessed by trained graders and a retinal specialist using protocols developed
      for large epidemiologic studies. Kidney function measurements and information on
      traditional and nontraditional risk factors for decreased kidney function were
      obtained from the CRIC study. RESULTS: Greater severity of retinopathy was
      associated with lower estimated glomerular filtration rate after adjustment for
      traditional and nontraditional risk factors. The presence of vascular
      abnormalities usually associated with hypertension was also associated with lower
      estimated glomerular filtration rate. We found no strong direct relationship
      between estimated glomerular filtration rate and average arteriolar or venular
      calibers. CONCLUSIONS: Our findings show a strong association between severity of
      retinopathy and its features and level of kidney function after adjustment for
      traditional and nontraditional risk factors for chronic kidney disease,
      suggesting that retinovascular pathology reflects renal disease.

PMID- 22965595
TI  - Clinical characteristics of a large choroideremia pedigree carrying a novel CHM
      mutation.
AB  - OBJECTIVE: To describe a large family with a novel mutation in CHM. METHODS:
      Family members were characterized using clinical examination, wide-field fundus
      photography, wide-field autofluorescence, and spectral domain optical coherence
      tomography. The CHM mutation was identified with the National Institutes of
      Health-sponsored eyeGene program. RESULTS: A novel nonsense CHM mutation
      (T1194G), resulting in a premature stop (Y398X) and loss of the final one-third C
      terminal portion of the protein, was identified. A large pedigree was generated
      from information provided by the twice-married proband. Seven men (aged 27-39
      years) and 7 women (aged 22-89 years) were evaluated. Affected men showed
      characteristic peripheral chorioretinal atrophy with islands of macular sparing.
      Female carriers exhibited a wide range of variability, from mild pigmentary
      alterations to significant chorioretinal atrophy with severe vision loss. Older
      women tended to have a more severe phenotype. Autofluorescence demonstrating
      subfoveal loss or absence of retinal pigment epithelium correlated with vision
      loss in both sexes. Spectral domain optical coherence tomography demonstrated
      dynamic changes and remodeling of the outer retina over time, including focal
      thickening, drusenlike deposits, and disruption to photoreceptor inner segment
      and outer segment junctions in young female carriers. CONCLUSIONS: CHM (T1194G)
      is a novel mutation that manifests a wide range of phenotypic variability in a
      single family with a trend toward more severe phenotypes in older female
      carriers. Our findings emphasize the importance of considering X-linked diseases
      by carefully evaluating pedigrees in women with severe manifestations of disease.
      CLINICAL RELEVANCE: These findings demonstrate a novel CHM mutation that
      emphasizes severe posterior pole carrier phenotypes, age-related changes, and
      early choroideremia disease.

PMID- 22965596
TI  - The ophthalmologist of the future.
AB  - Who are the ophthalmologists of the future? How will the new generation practice?
      How will they interact with their professional organizations? What part will
      technology play in their lives and professions? A new paradigm is in place that
      will dramatically affect ophthalmologists' answers to these questions going
      forward. Given the uncertainty of our future professional lives, it is vital that
      we anticipate, contemplate, and formulate a plan. To begin this process, the
      Knapp Symposium at the 2011 Annual Meeting of the American Ophthalmological
      Society was devoted to a discussion of the ophthalmologist of the future.

PMID- 22965597
TI  - The ophthalmic practice of the future.
AB  - How will the ophthalmologist of the future practice? What will be the effect of
      government policy? How will this impact the mix of health care providers
      responsible for the delivery of eye care to patients? What part will health
      record technology play in clinical practice? These topics were discussed at the
      Knapp Symposium of the 2011 Annual Meeting of the American Ophthalmological
      Society. The health care system within which ophthalmology will be practiced will
      be radically different, ruled by changes in collaboration, communication, and
      practice guidelines. Given the coming uncertainty of our professional lives, it
      is vital that we anticipate, contemplate, and plan for our futures.

PMID- 22965598
TI  - An expanded view of infantile esotropia: bottoms up!
AB  - A recent editorial in the Archives assigned the primary pathogenesis of infantile
      esotropia to the visual cortex. This analysis addresses the limitations of this
      timeworn view and advances the perspective that infantile esotropia is a cortico
      mesencephalic-cerebellar disorder wherein binocular cortical maldevelopment
      permits atavistic subcortical visual pathways to remain operational. This
      integrated neuroanatomical model predicts that primary neurodevelopmental
      disorders involving the accessory optic system or its connections to the
      cerebellum can also give rise to infantile esotropia.

PMID- 22965599
TI  - The ophthalmologist and ophthalmic practice of the future.

PMID- 22965600
TI  - Interview with Paul R. Lichter, MD. Interwed by George B Bartley.

PMID- 22965601
TI  - Infectious nontuberculous serpiginous choroiditis.

PMID- 22965602
TI  - Periocular epithelioid hemangioma: response to bevacizumab and vascular
      pathogenesis.

PMID- 22965603
TI  - Whipple disease with crystalline keratopathy and chronic uveitis.

PMID- 22965604
TI  - Utility of large spot binocular indirect laser delivery for peripheral
      photocoagulation therapy in children.
AB  - The purpose of this article is to demonstrate the utility of the large spot size
      (LSS) setting using a binocular laser indirect delivery system for peripheral
      ablation in children. One patient with bilateral retinopathy of prematurity
      received photocoagulation with standard spot size burns placed adjacently to LSS
      burns. Using a pixel analysis program called Image J on the Retcam picture, the
      areas of each retinal spot size were determined in units of pixels, giving a
      standard spot range of 805 to 1294 pixels and LSS range of 1699 to 2311 pixels.
      Additionally, fluence was calculated using theoretical retinal areas produced by
      each spot size: the standard spot setting was 462 mJ/mm2 and the LSS setting was
      104 mJ/mm2. For eyes with retinopathy of prematurity, our study shows that LSS
      laser indirect delivery halves the number of spots required for treatment and
      reduces fluence by almost one-quarter, producing more uniform spots.

PMID- 22965606
TI  - Epibulbar rosai-dorfman disease: novel manifestation and treatment.

PMID- 22965607
TI  - Myopic peripapillary sinkhole: prolapse of retinal nerve fiber layer and
      posterior vitreous into a sclerochoroidal hollow causing peripapillary choroidal
      thickening and cavitation.

PMID- 22965608
TI  - Progression of an acquired vitelliform lesion to a full-thickness macular hole
      documented by eye-tracked spectral-domain optical coherence tomography.

PMID- 22965609
TI  - Paraneoplastic optic neuropathy from cutaneous melanoma detected by positron
      emission tomographic and computed tomographic scanning.

PMID- 22965610
TI  - Leuprolide monotherapy for choroidal metastasis from prostate adenocarcinoma.

PMID- 22965611
TI  - Reduction of vascular endothelial growth factor a in human breast milk after
      intravitreal injection of bevacizumab but not ranibizumab.

PMID- 22965612
TI  - Conjunctival granulomatosis in churg-strauss syndrome.

PMID- 22965613
TI  - Angle involvement and glaucoma in patients with biopsy-proven iris melanoma: a
      response.

PMID- 22965615
TI  - Modification of silicone oil retention sutures in aphakic eyes with iris loss.

PMID- 22965617
TI  - The economics of the initial preventive physical examination in medicare.

PMID- 22965619
TI  - Genotoxic and mutagenic effects of permethrin in mice: micronuclei analysis in
      peripheral blood erythrocytes.
AB  - Pyrethroids such as permethrin are synthetic compounds widely used in the
      agriculture of many countries to combat plagues and in domestic products, such as
      acaricides. Not so long ago these chemicals were characterized as non-toxic for
      non-target organisms; however, recent studies have showed that these compounds
      could present toxic potential for many organisms. In this sense, this study
      presents genotoxic and mutagenic potential of permethrin administered
      intraperitoneally in mice under artificial conditions by the use of micronucleus
      assay in the peripheral blood of these animals. The mice were divided into five
      groups: group I = negative control (distilled water), group II = positive control
      (cyclophosphamide), group III = 30% of permethrin LD(50) (96 mg/kg), group IV =
      50% of permethrin LD(50) (160 mg/kg), and group V = 80% of permethrin LD(50) (256
      mg/kg). The peripheral blood was collected 24, 48, and 72 h after treatment.
      Results showed that all the tested permethrin dosages presented genotoxic and
      mutagenic effects 24 h after treatment, which would contradict the classification
      of this chemical product as moderately toxic, i.e., unable to cause damages to
      the cell DNA.

PMID- 22965620
TI  - Minimally invasive ultrasound-guided carpal tunnel release: a cadaver study.
AB  - BACKGROUND: Carpal tunnel syndrome is a common condition frequently requiring
      surgical intervention. We describe a new minimally invasive surgical technique
      for carpal tunnel release utilizing ultrasound (US) visualization. METHODS: The
      technique was performed on 20 fresh frozen cadaver specimens. A surgical metallic
      probe with a "U"-shaped trough and upward curved distal tip was precisely
      positioned in the carpal tunnel with US guidance followed by division of the
      flexor retinaculum (FR) with a "V"-shaped scalpel. RESULTS: Complete division of
      the FR was confirmed by US. Dissection performed on the specimens confirmed
      complete release of FR and absence of neurovascular injury. The distance from the
      division of the FR to these structures, the "safety margins," was measured.
      CONCLUSIONS: This new technique for carpal tunnel release appears to combine the
      safety and efficacy of open carpal tunnel surgery with the advantages of the
      minimally invasive techniques.

PMID- 22965621
TI  - Absorption by isolated ferric heme nitrosyl cations in vacuo.

PMID- 22965622
TI  - Project heli?dx(w)/Healthy Hearts Across Generations: development and evaluation
      design of a tribally based cardiovascular disease prevention intervention for
      American Indian families.
AB  - American Indian and Alaska Native (AIAN) populations are disproportionately at
      risk for cardiovascular disease (CVD), diabetes, and obesity, compared with the
      general US population. This article describes the heli?dx(w)/Healthy Hearts
      Across Generations project, an AIAN-run, tribally based randomized controlled
      trial (January 2010-June 2012) designed to evaluate a culturally appropriate CVD
      risk prevention program for AI parents residing in the Pacific Northwest of the
      United States. At-risk AIAN adults (n = 135) were randomly assigned to either a
      CVD prevention intervention arm or a comparison arm focusing on increasing family
      cohesiveness, communication, and connectedness. Both year-long conditions
      included 1 month of motivational interviewing counseling followed by personal
      coach contacts and family life-skills classes. Blood chemistry, blood pressure,
      body mass index, food intake, and physical activity were measured at baseline and
      at 4- and 12-month follow-up times.

PMID- 22965624
TI  - Flavone reduces the production of virulence factors, staphyloxanthin and alpha
      hemolysin, in Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading cause of nosocomial infections due to its
      resistance to diverse antibiotics. This bacterium produces a large number of
      extracellular virulence factors that are closely associated with specific
      diseases. In this study, diverse plant flavonoids were investigated to identify a
      novel anti-virulence compound against two S. aureus strains. Flavone, a backbone
      compound of flavonoids, at subinhibitory concentration (50 MUg/mL), markedly
      reduced the production of staphyloxanthin and alpha-hemolysin. This
      staphyloxanthin reduction rendered the S. aureus cells 100 times more vulnerable
      to hydrogen peroxide in the presence of flavone. In addition, flavone
      significantly decreased the hemolysis of human red blood by S. aureus, and the
      transcriptional level of alpha-hemolysin gene hla and a global regulator gene sae
      in S. aureus cells. This finding supported the usefulness of flavone as a
      potential antivirulence agent against antibiotic-resistant S. aureus.

PMID- 22965623
TI  - Quorum sensing circuit and reactive oxygen species resistance in Deinococcus sp.
AB  - Genus Deinococcus is characterized by an increased resistance toward reactive
      oxygen species (ROS). The chromosome of five strains belonging to this genus has
      been sequenced and the presence of a luxS-like gene was deduced from their genome
      sequences. The aim of this study was to assess if a complete QS circuit is
      present in Deinococcus sp. and if this QS is associated with ROS. Primers for
      searching luxS-like gene and the putative receptor gene, namely ai2R, were
      designed. AI-2 signal production was evaluated by luminescence analysis using
      Vibrio harveyi BB170 as reporter strain. AI-2 signal was also evaluated by
      competitive assays using cinnamaldehyde, ascorbic acid, and 3-mercaptopropionic
      acid as interfering molecules. Potassium tellurite and metronidazole were used as
      oxidative stressors. A luxS-like gene as well as an ai2R gene was detected in
      strain UDEC-P1 by PCR. Cell-free supernatant of strain UDEC-P1 culture induced
      luminescence in V. harveyi BB170, and this property was inhibited with the three
      interfering molecules. The oxidative stressors metronidazole and potassium
      tellurite decreased Deinococcus sp. viability, but increased luminescence of the
      reporter strain. The results demonstrate that both a functional luxS-like gene
      and a putative receptor for AI-2 signal are present in Deinococcus sp. strain
      UDEC-P1. This finding also suggests that a complete QS circuit is present in this
      genus, which could be related to oxidative stress.

PMID- 22965625
TI  - Diagnostic performance of vertebral fracture assessment by the lunar iDXA scanner
      compared to conventional radiography.
AB  - The purpose of this study was to evaluate the diagnostic performance of vertebral
      fracture assessment (VFA) using the Lunar iDXA scanner. Conventional spinal
      radiographs and images acquired by dual-energy X-ray absorptiometry (DXA) of 350
      subjects (269 females, 81 males) were evaluated by two different readers. We
      visualized 4,476/4,550 (98.4 %) vertebrae from T4 to L4 on VFA images compared to
      4,535/4,550 (99.7 %) on radiographs. Among the visualized vertebrae, 205/4,535
      (4.5 %) and 190/4,476 (4.2 %) were identified as nonfracture deformities by
      reading of radiographs and VFA, respectively. Vertebral fractures (VFs) were 231
      in 126 patients and 228 in 125 patients by semiquantitative assessment of
      radiographs (SQ-Rx) and by VFA, respectively. There was excellent agreement
      between the two techniques and high diagnostic performance of VFA both on a per
      vertebra basis (k score = 0.984, 95 % CI 0.972-0.996, sensitivity 98.68 %,
      specificity 99.91 %, PPV 98.25 %, NPV 99.93 %) and on a per-patient basis (k
      score = 0.957, 95 % CI 0.925-0.988, sensitivity 96.83 %, specificity 98.66 %, PPV
      97.60 %, NPV 98.22 %). In older patients (>=65 years) affected by moderate or
      severe osteoarthritis, SQ-Rx and VFA identified 96 VFs and 95 versus 90 vertebral
      deformities, respectively. This study demonstrates that most vertebrae are
      evaluable using the iDXA scanner, with improved VFA diagnostic performance even
      in discriminating mild VFs from vertebral deformities. Therefore, VFA may be
      appropriate as an alternative to conventional radiography in patients at high
      risk of VF who are undergoing DXA bone densitometry and in the follow-up of
      osteoporotic patients on treatment.

PMID- 22965626
TI  - Effective absorption modeling in relative bioavailability study risk assessment.
AB  - Absorption modeling is an excellent strategic fit to perform a risk assessment
      for relative bioavailability (RBA) studies as it provides direct input into the
      question that is at the core of the RBA decision, namely, how does the absorption
      of the test drug product compare to the reference and is it likely to be
      different enough to justify an RBA study. The main limitation to absorption
      modeling in risk assessment is the inherent uncertainty associated with modeling.
      The extent to which the absorption modeling is integrated into the risk
      assessment should depend on the level of confidence in the modeling. It is
      difficult, however, to quantify the level of confidence on a case by case basis.
      The effective application of absorption modeling for RBA risk assessment
      therefore requires a general understanding of when modeling is expected to be
      reliable and also how to build reliability directly into the modeling. This paper
      describes a framework for effective modeling in RBA risk assessment that is based
      on four fundamental building blocks: (1) relate severity of drug product change
      and API properties to reliability of modeling, (2) use critical model variables
      to express the critical differences in the drug products, (3) generate a fraction
      absorbed response surface expressed in terms of the critical model variables to
      evaluate the relative performance of the drug products, and (4) tie the first
      three building blocks together by following good model building practices that
      assure the highest quality model is built. The building blocks are demonstrated
      by a simple but common example of a change in solid state from free base to HCl
      salt.

PMID- 22965627
TI  - Self-assembly of nano-sized neutral metal-organic macrocycles from bis(beta
      diketone) ligands.
AB  - It's hip to be square: Self-assembly of bis(beta-diketone) linkers with 90
      degrees  or 120 degrees  angles and square-planer-coordinated divalent copper
      ions gives rise to the formation of nano-sized M(4)L(4)-type neutral metal
      organic supramolecular macrocycles, which show promise towards encapsulating
      solvent or guest molecules.

PMID- 22965628
TI  - [Ultrasonographically guided biopsy procedures: current practice in hospitals
      with established departments of gastroenterology].
AB  - OBJECTIVE: Ultrasonographically guided adominal biopsies are a frequent daily
      procedure in German hospitals. There are, however, few guidelines or
      recommendations for these common procedures. The oive of the current study was to
      assess current practice with respect to ultrasonographically guided biopsy
      procedures in a survey of hospitals with established departments of
      gastroenterology or with over 500 beds. MATERIAL AND METHOD: A questionnaire
      addressing the preparation for, procedure during, and post-interventional
      monitoring following ultrasonographically guided biopsies was mailed to 349
      German hospitals. The response rate was 51 % (n = 177). RESULTS: Establishment of
      an intravenous access is standard in 51.2 % (88/172) of the hospitals. Sedation
      analgesia is standard in 19.1 % (33/173) of the hospitals and is an option in a
      further 60.1 % (104/173). Local anesthesia is performed in 84.8 % (145/171) of
      the hospitals. A dedicated transducer for targeted biopsy is used in 40.6 %
      (81/176) of the hospitals, while 29.5 % (52/176) use a separate biopsy bracket
      attached to the probe. In 80.6 % (141/175) of the hospitals, a minimum platelet
      count of 50,000/uL is required. A minimum of 50 % is used as limit for quick in
      86.5 % (147/170) of the hospitals. A value of 1 - 1.5 for the international
      normalized ratio (INR) is most commonly used in the hospitals. A partial
      thromboplastin time (PTT) between 28 and 50 sec. is used as the upper limit.
      Interruption of anticoagulants is handled in a very heterogeneous manner.
      Postinterventional monitoring following biopsy in ambulatory patients ranges from
      two to 24 hours. CONCLUSION: Our survey shows relevant differences in
      preparation, execution and postinterventional monitoring in ultrasonographically
      guided biopsy procedures as routinely performed in German hospitals. There seems
      to be a need for a guideline standardising ultrasonographically guided biopsy
      procedures.

PMID- 22965629
TI  - Subclinical ascites defines an intermediate stage between compensated and
      decompensated cirrhosis.
AB  - BACKGROUND: Clinical detection of ascites is a sign of decompensation and
      correlates with shorter survival in patients with cirrhosis. However, the
      prognostic relevance of sole detection of ascites by ultrasound (subclinical
      ascites) is not investigated so far. The aim of the study was to investigate the
      prognostic relevance of subclinical ascites detected by ultrasound in comparison
      to absent or clinically detectable ascites in patients with cirrhosis. METHODS:
      Between 11/1995 and 11/2004 a total of 729 patients with cirrhosis underwent
      sonographic and hemodynamic (including measurement of HVPG) evaluation. The mean
      follow up time was 47 months (range: 0.13 - 131). Kaplan-Meier survival curves
      and multivariate analysis were used to investigate differences. RESULTS: 443
      patients were included in the final investigation - 153 patients without ascites,
      38 with subclinical ascites and 252 patients with clinical ascites. Kaplan Meier
      survival curves were significantly different between the three groups (p <
      0.001). Interestingly, patients with subclinical ascites had similar values
      compared to patients with clinical ascites regarding parameters of portal
      hypertension (HVPG) and liver dysfunction (INR), while parameters of systemic and
      renal dysfunction (heart beat, creatinin, serum sodium) were similar to patients
      without ascites. MELD, Child-Pugh score and ascites were independent predictors
      of mortality in the entire group, while Child-Pugh score and HVPG were
      independent factors in the subclinical ascites group. CONCLUSION: Detection of
      subclinical ascites by ultrasound allows the identification of a group of
      cirrhotic patients with intermediary survival compared to patients without or
      with clinical ascites. This group of patients is characterized by severe portal
      hypertension but absence of systemic and renal dysfunction.

PMID- 22965630
TI  - [S3 Guideline on "sedation in gastrointestinal endoscopy": how much does the new
      guideline cost in everyday hospital work? A calculation model and analysis of
      implementation in 2011 among ALGK members].
AB  - BACKGROUND: The introduction of the S3 guideline on "Sedation in Gastrointestinal
      Endoscopy" in 2008 led to substantial organisational, structural, staffing
      related, financial, and legal changes in the everyday work of departments of
      gastrointestinal endoscopy. This study examines the economic effects of this and
      the change in the legal situation. In addition, the extent to which the guideline
      has been implemented was assessed using an electronic questionnaire circulated to
      the members of the Working Group of Head Gastroenterologists in Hospitals (ALGK).
      METHODS: The increased financial burden in the area of staff costs resulting from
      correct compliance with the sedation guideline was calculated using research
      figures from an endoscopy department in a maximum-care non-university hospital,
      dating from 2009. Interpretation of the legal implications of the guideline was
      provided by lawyers familiar with medical legislation. The question of the extent
      to which the guideline has been implemented in everyday clinical practice in
      endoscopy departments in 2011 was investigated using an evaluation questionnaire
      sent to the members of the ALGK. RESULTS: Implementation of the S3 sedation
      guideline leads to a substantial increase in the financial burden in the area of
      staff costs. Assuming 8000 in-patient endoscopy procedures, a conservative
      estimate indicates extra costs amounting to ? 257 462.- per year (gross costs for
      the employer). The analysis of the questionnaire sent to ALGK members on the
      implementation of the S3 guideline 3 years after its publication showed that its
      major points, particularly the deployment of a third staff member for sedation,
      have not been acted on. CONCLUSIONS: The S3 guideline on "Sedation in
      Gastrointestinal Endoscopy" leads to a substantial increase in the financial
      burden in the area of staff costs by requiring the presence of a third person
      exclusively concerned with sedation. This recommendation was issued by the
      authors of the guideline without any evidence being available. In addition, it
      leads to a clear change in the legal situation, which in case of claims arising
      is associated with substantial implications for the physician responsible. The
      questionnaire evaluation among the members of the ALGK showed that the guideline
      has not so far been implemented in in-patient gastroenterology.

PMID- 22965631
TI  - IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma.
AB  - IgG4-related disease has gained increased attention worldwide. While the initial
      focus was on autoimmune pancreatitis which was first described in Asian
      populations and turned out to be of relevance in Western populations too, the
      scope has recently broadened towards a notion of a multi-systemic disease with
      very diverse manifestations such as autoimmune pancreatitis, IgG4-related
      sclerosing cholangitis (IgG4-SC), retroperitoneal fibrosis and tubulointerstitial
      nephritis. IgG4-SC (also known as IgG4-associated cholangitis, IAC) represents a
      rare but clinically challenging differential diagnosis in patients with
      obstructive jaundice and proximal extra- or intrahepatic biliary strictures which
      can be mistaken for cholangiocarcinoma (CC). We present the case of a 79-year-old
      male patient who presented with obstructive jaundice and biliary strictures at
      the hepatic duct bifurcation without any evidence for autoimmune pancreatitis and
      without elevation of serum IgG4-concentrations who underwent hemihepatectomy for
      suspected CC. However, on histological examination of the resection specimen CC
      could not be confirmed. It was only after several episodes of obstructive
      jaundice had reoccurred that the diagnosis of IgG4-SC could be established by
      reexamination of the surgical specimen which showed extensive infiltration with
      IgG4-positive plasma cells. Appropriate medical treatment with steroids and
      azathioprine led to complete remission of the disease. Early recognition of IgG4
      SC can save patients from potential harmful and unnecessary surgical
      interventions. Here we describe the clinical features of this rare case of IgG4
      SC with extensive liver tissue infiltration with IgG4-positive cells but without
      elevated serum IgG4 concentration or evidence of autoimmune pancreatitis. We
      describe diagnostic criteria for IgG4-SC and review recent insights in
      pathophysiology and treatment options.

PMID- 22965632
TI  - [Enteroscopy and imaging in sclerosing mesenteritis].
AB  - Sclerosing mesenteritis is a rare, benign, and chronic fibrosing inflammatory
      disease of the mesenteric fatty tissue. Its aetiology is unknown. In the present
      report we describe a 56-year-old women who presented with postprandial abdominal
      pain, and weight loss. Ultrasound, computed tomography, and magnetic resonance
      imaging revealed a mesenteric mass of 15 cm. The findings were typical for this
      disease. Additionally the patient underwent a single ballon enteroscopy in which
      the mucosa showed a considerable hyperergic reaction. The histological
      examination of the ileum was appropriate to support the suspicion. The patient's
      symptoms responded to a therapy with tamoxifen.

PMID- 22965633
TI  - Treatment of hepatocellular carcinoma with sorafenib - focus on special
      populations and adverse event management.
AB  - Sorafenib, a receptor tyrosine kinase-inhibitor with anti-proliferative and anti
      angiogenic activity, is currently the only approved systemic treatment for
      patients with hepatocellular carcinoma. It inhibits downstream signaling of VEGFR
      2, PDGFR, c-Kit receptors and BRAF. Over the last four years comprehensive
      experience with sorafenib in this indication has been accumulated. In this review
      we discuss the current data on the use of sorafenib in patients with advanced HCC
      including special patient populations such as patients with impaired liver
      function, patients after transplantation, and others. The most frequent side
      effects and practical tips on how to manage them are discussed in detail. In
      addition, we summarize the current experimental data on the use of sorafenib in
      combination treatment, e. g., together with transarterial chemoembolisation or
      other targeted agents.

PMID- 22965634
TI  - The role of bile acids in the neoplastic progression of Barrett's esophagus - a
      short representative overview.
AB  - Barrett's esophagus (BE) is an intestinal metaplasia of the distal esophagus in
      which squamous cells are replaced by a columnar epithelium. It is considered as a
      premalignant lesion, which can lead to esophageal adenocarcinoma, a very
      aggressive type of cancer, and can often be found in patients with gastro
      esophageal reflux disease (GERD). In spite of the widespread use of acid
      suppressing therapy with proton pump inhibitors, the incidence of adenocarcinoma
      has been steadily rising during the last 30 years. So, it can strongly be
      suggested that refluxed material other than acid might contribute to the
      progression of cancer within Barrett's esophagus. Along with gastric acid, bile
      acids enter the esophagus during an episode of reflux, and bile acids may be
      important in carcinogenesis. In their refluxates, patients with GERD and BE show
      high concentrations of the hydrophobic bile salt deoxycholic acid (DCA), which
      has cytotoxic effects and is able to induce DNA damage in different cell types.
      Other bile acids, like the hydrophilic urodeoxycholic acid (UDCA), have been
      therapeutically used to treat cholestatic liver diseases and to prevent colon
      carcinoma. This article reviews the effects of bile acids and points out new
      perceptions in the progression of Barrett's-associated carcinogenesis.

PMID- 22965635
TI  - Disruptive behavior in childhood and socioeconomic position in adulthood: a
      prospective study over 27 years.
AB  - OBJECTIVES: We examined whether childhood disruptive behavior (aggressiveness,
      hyperactivity and social adjustment), predicts adulthood socioeconomic position
      (SEP), i.e., educational level, occupational status and income and social
      mobility. METHODS: Social mobility was defined by comparing the participants'
      adulthood socioeconomic position with that of their parents ("intergenerational
      social mobility"). The subjects were derived from a population-based cohort study
      (N = 3,600) and our sample consisted of 782 participants (403 women) aged 3-9
      years at baseline and were followed until they were aged 30-36. RESULTS: High
      childhood aggression associated with low educational level and occupational
      status suggesting an early beginning negative tracking of aggressive behavior.
      High hyperactivity and poor social adjustment predicted adulthood low
      occupational status proposing a more slow effect on adulthood SEP. No
      associations between disruptive behavior and income-related mobility were found,
      but high hyperactivity associated with educational downward drift, whereas high
      aggression and low social adjustment related with occupational downward drift.
      CONCLUSIONS: Results suggest that childhood disruptive behavior may have long
      lasting negative effects. In order to reduce the adverse effects of disruptive
      behavior, early intervention of problematic behavior becomes salient.

PMID- 22965636
TI  - Comparative efficiency of microbial enzyme preparations versus pancreatin for in
      vitro alimentary protein digestion.
AB  - Utilisation of microbial enzymes may represent an alternative strategy to the use
      of conventional pancreatin obtained from pig pancreas for the treatment of severe
      pancreatic insufficiency. In this study, we focused on the capacity of two
      microbial preparations for their capacity to digest alimentary proteins (caseins
      and soya proteins) in comparison with pancreatin. These microbial enzymatic
      preparations were found to be able to generate small, medium-size and larger
      polypeptides from caseins and soya proteins but were inactivated at pH 3.0. As
      determined by Liquid Chromatography-Mass Spectrometry analysis, microbial enzymes
      generated very different peptides from caseins when compared with peptides
      generated through pancreatin action. These microbial preparations were
      characterised by relatively low trypsin- and low carboxypeptidase-like activities
      but high chymotrypsin-like activities and strong capacity for cleavage of caseins
      at the methionine sites. Although the efficiency of these microbial preparations
      to increase the rate of absorption of nitrogen-containing compounds in severe
      pancreatic insufficiency remains to be tested in vivo, our in vitro data indicate
      proteolytic capacities of such preparations for alimentary protein digestion.

PMID- 22965637
TI  - Transformation of the naturally occurring frog skin peptide, alyteserin-2a into a
      potent, non-toxic anti-cancer agent.
AB  - Alyteserin-2a (ILGKLLSTAAGLLSNL.NH(2)) is a cationic, amphipathic alpha-helical
      cell-penetrating peptide, first isolated from skin secretions of the midwife toad
      Alytes obstetricans. Structure-activity relationships were investigated by
      synthesizing analogs of alyteserin-2a in which amino acids on the hydrophobic
      face of the helix were replaced by L-tryptophan and amino acids on the
      hydrophilic face were replaced by one or more L-lysine or D-lysine residues. The
      Trp-containing peptides display increased cytotoxic activity against non-small
      cell lung adenocarcinoma A549 cells (up to 11-fold), but hemolytic activity
      against human erythrocytes increases in parallel. The potency of the N15K analog
      against A549 cells (LC(50) = 13 MUM) increases sixfold relative to alyteserin-2a
      and the therapeutic index (ratio of LC(50) for erythrocytes and tumor cells)
      increases twofold. Incorporation of a D-Lys(11) residue into the N15K analog
      generates a peptide that retains potency against A549 cells (LC(50) = 15 MUM) but
      whose therapeutic index is 13-fold elevated relative to the native peptide.
      [G11k, N15K] alyteserin-2a is also active against human hepatocarcinoma HepG2
      cells (LC(50) = 26 MUM), breast adenocarcinoma MDA-MB-231 cells (LC(50) = 20
      MUM), and colorectal adenocarcinoma HT-29 cells (LC(50) = 28 MUM). [G11k, N15K]
      alyteserin-2a, in concentrations as low as 1 MUg/mL, significantly (P < 0.05)
      inhibits the release of the immune-suppressive cytokines IL-10 and TGF-beta from
      unstimulated and concanavalin A-stimulated peripheral blood mononuclear cells.
      The data suggest a strategy of increasing the cationicity while reducing the
      helicity of naturally occurring amphipathic alpha-helical peptides to generate
      analogs with improved cytotoxicity against tumor cells but decreased activity
      against non-neoplastic cells.

PMID- 22965638
TI  - Challenges in quantitative analyses for volatile organic compounds bound to
      lipocalins.
AB  - In this communication, I describe the challenges in quantitative analyses for
      volatile organic compounds in mouse urine, which are primarily caused by the
      presence of the major urinary proteins, a lipocalin subfamily, that sequester
      volatile ligands. The analyses of volatile compounds in mouse urine have been
      performed since the late 1970s. However, none of them considered the binding
      interactions of the quantified compounds with the urinary proteins. Some volatile
      ligands are tightly bound to the proteins and may not be extracted completely by
      organic solvents. The amounts of volatile ligands measured by external standard
      calibration represent those of the unbound ligands in the headspace, not the
      total amounts in urine. Addition of internal standards displaces ligands bound to
      the proteins, resulting in a completely different volatile profile. Normalization
      of volatile compounds using relative peak area (or height) ratios may not be used
      in the conditions where displacement of ligands bound to the proteins occurs.
      Because of the unique chemical properties of mouse urine, I have not been able to
      find a good quantification method for the volatile compounds released from mouse
      urine. I hope that the identification of these issues will stimulate others to
      come up with novel approaches.

PMID- 22965639
TI  - Determination of critical parameters in platelet margination.
AB  - An investigation of margination dependence on hematocrit, platelet shape, and
      viscosity ratio of plasma to cytoplasm is presented. Whole blood is modeled as a
      suspension of deformable red blood cells (RBCs) and rigid platelets in a viscous
      liquid. The fluid phase is simulated using the lattice-Boltzmann method, the RBC
      membranes are modeled with a coarse-grained spectrin-link method, and the
      dynamics of rigid particles are updated using Newton's equations of motion for
      axisymmetric shapes. The results emphasize that an increase in hematocrit
      increases the rate of margination. The viscosity ratio between the interior
      cytoplasm and suspending fluid can considerably alter the rate of margination.
      The aspect ratio of surrogate platelet particles influences the rate of
      margination as well. Spherical particles tend to migrate more quickly than disks.
      Highly viscous or rigid RBCs slow down margination.

PMID- 22965640
TI  - A novel left heart simulator for the multi-modality characterization of native
      mitral valve geometry and fluid mechanics.
AB  - Numerical models of the mitral valve have been used to elucidate mitral valve
      function and mechanics. These models have evolved from simple two-dimensional
      approximations to complex three-dimensional fully coupled fluid structure
      interaction models. However, to date these models lack direct one-to-one
      experimental validation. As computational solvers vary considerably, experimental
      benchmark data are critically important to ensure model accuracy. In this study,
      a novel left heart simulator was designed specifically for the validation of
      numerical mitral valve models. Several distinct experimental techniques were
      collectively performed to resolve mitral valve geometry and hemodynamics. In
      particular, micro-computed tomography was used to obtain accurate and high
      resolution (39 MUm voxel) native valvular anatomy, which included the mitral
      leaflets, chordae tendinae, and papillary muscles. Three-dimensional
      echocardiography was used to obtain systolic leaflet geometry. Stereoscopic
      digital particle image velocimetry provided all three components of fluid
      velocity through the mitral valve, resolved every 25 ms in the cardiac cycle. A
      strong central filling jet (V ~ 0.6 m/s) was observed during peak systole with
      minimal out-of-plane velocities. In addition, physiologic hemodynamic boundary
      conditions were defined and all data were synchronously acquired through a
      central trigger. Finally, the simulator is a precisely controlled environment, in
      which flow conditions and geometry can be systematically prescribed and resultant
      valvular function and hemodynamics assessed. Thus, this work represents the first
      comprehensive database of high fidelity experimental data, critical for extensive
      validation of mitral valve fluid structure interaction simulations.

PMID- 22965641
TI  - Analysis of kinetics of dihydroethidium fluorescence with superoxide using
      xanthine oxidase and hypoxanthine assay.
AB  - Superoxide (O(2) (-)) is an important reactive oxygen species (ROS), and has an
      essential role in physiology and pathophysiology. An accurate detection of O(2) (
      ) is needed to better understand numerous vascular pathologies. In this study, we
      performed a mechanistic study by using the xanthine oxidase (XOD)/hypoxanthine
      (HX) assay for O(2) (-) generation and a O(2) (-) sensitive fluorescent dye
      dihydroethidium (DHE) for O(2) (-) measurement. To quantify O(2) (-) and DHE
      interactions, we measured fluorescence using a microplate reader. We conducted a
      detailed reaction kinetic analysis for DHE-O(2) (-) interaction to understand the
      effect of O(2) (-) self-dismutation and to quantify DHE-O(2) (-) reaction rate.
      Fluorescence of DHE and 2-hydroethidium (EOH), a product of DHE and O(2) (-)
      interaction, were dependent on reaction conditions. Kinetic analysis resulted in
      a reaction rate constant of 2.169 +/- 0.059 * 10(3) M(-1) s(-1) for DHE-O(2) (-)
      reaction that is ~100* slower than the reported value of 2.6 +/- 0.6 * 10(5) M(
      1) s(-1). In addition, the O(2) (-) self-dismutation has significant effect on
      DHE-O(2) (-) interaction. A slower reaction rate of DHE with O(2) (-) is more
      reasonable for O(2) (-) measurements. In this manner, the DHE is not competing
      with superoxide dismutase and NO for O(2) (-). Results suggest that an accurate
      measurement of O(2) (-) production rate may be difficult due to competitive
      interference for many factors; however O(2) (-) concentration may be quantified.

PMID- 22965642
TI  - Breast cancer and other neoplasms in women with neurofibromatosis type 1: a
      retrospective review of cases in the Detroit metropolitan area.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common cancer predisposing
      syndromes with an incidence of 1 in 3,500 worldwide. Certain neoplasms or
      malignancies are over-represented in individuals with NF1; however, an increased
      risk of breast cancer has not been widely recognized or accepted. We identified
      76 women with NF1 seen in the Henry Ford Health System (HFHS) from 1990 to 2009,
      and linked them to the Surveillance Epidemiology and End Results (SEER) registry
      covering the metropolitan Detroit area. Fifty-one women (67%) were under age 50
      years at the time of data analysis. Six women developed invasive breast cancer
      before age 50, and three developed invasive breast cancer after age 50. Using
      standardized incidence ratios (SIRs) calculated based on the SEER age-adjusted
      invasive breast cancer incidence rates, our findings demonstrated a statistically
      significant increase of breast cancer incidence occurring in NF1 women (SIR =
      5.2; 95% CI 2.4-9.8), and this relative increase was especially evident among
      those with breast cancer onset under age 50 (SIR = 8.8; 95% CI 3.2-19.2). These
      data are consistent with other reports suggesting an increase in breast cancer
      risk among females with NF1, which indicate that breast cancer screening
      guidelines should be evaluated for this potentially high-risk group.

PMID- 22965643
TI  - The effects of substituents on the geometry of pi-pi interactions.
AB  - We have designed and utilized a simple molecular recognition system to study the
      substituent effects in aromatic interactions. Recently, we showed that 3- and 3,5
      disubstituted benzoyl leucine diethyl amides with aromatic rings of varying
      electronic character organized into homochiral dimers in the solid state through
      a parallel displaced pi-pi interaction and two hydrogen bonds, but no such
      homochiral dimerization was observed for the unsubstituted case. This phenomenon
      supports the hypothesis that substituents stabilize pi-pi interactions regardless
      of their electronic character. To further investigate the origin of substituent
      effects for pi-pi interactions, we synthesized and crystallized a series of 4
      substituted benzoyl leucine diethyl amides. Surprisingly, only two of the 4
      substituted compounds formed homochiral dimers. A comparison among the 4
      substituted compounds that crystallized as homochiral dimers and their 3
      substituted counterparts revealed that there are differences in regard to the
      geometry of the aromatic rings with respect to each other, which depend on the
      electronic nature and location of the substituent. The crystal structures of the
      homochiral dimers that showed evidence of direct, local interactions between the
      substituents on the aromatic rings also displayed nonequivalent dihedral angles
      in the individual monomers. The crystallographic data suggests that such
      "flexing" may be the result of the individual molecules orienting themselves to
      maximize the local dipole interactions on the respective aromatic rings. The
      results presented here can potentially have broad applicability towards the
      development of molecular recognition systems that involve aromatic interactions.

PMID- 22965644
TI  - A new approach to achieve controlled ice nucleation of supercooled solutions
      during the freezing step in freeze-drying.

PMID- 22965645
TI  - Ultrasound imaging of infant sucking dynamics during the establishment of
      lactation.
AB  - BACKGROUND: Infant sucking problems are frequently implicated in early weaning
      during breastfeeding, yet our understanding of early sucking dynamics is limited.
      OBJECTIVE: This study aimed to describe infant sucking patterns during
      breastfeeding at secretory activation and determine whether they changed by the
      time of established lactation. METHODS: Sucking patterns and milk intake of 15
      breastfeeding infants were assessed on day 3.2 +/- 0.8 and later at follow-up,
      16.0 (11.3-22.8) days postpartum. Nipple diameters, tongue movement, nipple
      position, and suck rate during nutritive sucking (NS) and non-nutritive sucking
      (NNS) were measured from ultrasound scans of the intra-oral cavity during
      breastfeeding. Milk intake and LATCH scores were also recorded. RESULTS: As the
      tongue lowered during a suck cycle, the nipple increased in size (P < .001), milk
      flowed into the intra-oral space and the nipple moved closer to the hard-soft
      palate junction (P < .001). During NS, nipple diameters and the mid-tongue
      movement were greater than during NNS (P < .001). As the infant aged, the mid
      tongue lowered further (P = .002), suck rates became faster (P < .001) and milk
      intake increased (P = .004), however, no differences were seen for LATCH scores
      (P = .34). CONCLUSION: Differences in tongue movement between NS and NNS suggest
      that there is an altered sucking action when milk flow is absent. Similar sucking
      patterns at day 3 and during established lactation imply that infants have a
      mature sucking pattern in the early postpartum period.

PMID- 22965646
TI  - Tongue coblation via the ventral approach for obstructive sleep apnea-hypopnea
      syndrome surgery.
AB  - OBJECTIVES/HYPOTHESIS: To determine the safety and efficacy of tongue Coblation
      via the ventral approach in the treatment of hypopharyngeal obstruction for
      patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN:
      Prospective case-control study. METHODS: Tongue Coblation was performed under
      local anesthesia in one session in 40 inpatients diagnosed with OSAHS with
      predominant hypopharyngeal obstruction after failed uvulopalatopharyngoplasty. In
      the ventral approach (n = 20), only one puncture point was applied at the center
      of lingual frenulum, and 12 radiofrequency volumetric tissue reduction (RFVTR)
      lesions were implanted in the tongue. In the dorsal approach (n = 20), eight
      RFVTR lesions were distributed on the tongue. Using portable polysomnography
      (PSG) and the Epworth sleepiness questionnaire (ESQ), we followed 36 patients for
      1 year after the operation. Good outcome was defined as apnea-hypopnea index <20
      or reduction >50%. RESULTS: In the ventral approach, total energy was accumulated
      to 23,000 J in 12 lesions, with postoperative pain 2-3 by visual analog scale
      (VAS). There was only one case of moderate venous bleeding and hematoma. The ESQ
      comparison indicated subjective improvements in patients, and PSG showed a
      curative effect in 11 of 19 (61.11%, eight of 19 success plus three of 19
      responders), with a failure rate of eight of 19. By contrast, in the dorsal
      approach, total energy was 16,000 J, with postoperative pain 3-4 (VAS).
      Complications included mild to moderate tongue venous hematoma, severe infection
      of tongue, and temporary mild glossal deviation. A curative effect was seen in
      six of 17, with a failure rate of 11 of 17. CONCLUSIONS: Tongue Coblation via the
      ventral approach is an effective and safe technique to treat hypopharyngeal
      obstruction in OSAHS surgery.

PMID- 22965647
TI  - The chemical biology of phosphoinositide 3-kinases.
AB  - Since its discovery in the late 1980s, phosphoinositide 3-kinase (PI3K), and its
      isoforms have arguably reached the forefront of signal transduction research.
      Regulation of this lipid kinase, its functions, its effectors, in short its
      entire signaling network, has been extensively studied. PI3K inhibitors are
      frequently used in biochemistry and cell biology. In addition, many
      pharmaceutical companies have launched drug-discovery programs to identify
      modulators of PI3Ks. Despite these efforts and a fairly good knowledge of the
      PI3K signaling network, we still have only a rudimentary picture of the signaling
      dynamics of PI3K and its lipid products in space and time. It is therefore
      essential to create and use novel biological and chemical tools to manipulate the
      phosphoinositide signaling network with spatial and temporal resolution. In this
      review, we discuss the current and potential future tools that are available and
      necessary to unravel the various functions of PI3K and its isoforms.

PMID- 22965648
TI  - Physiologic monitoring practices during pediatric procedural sedation: a report
      from the Pediatric Sedation Research Consortium.
AB  - OBJECTIVES: To describe the frequency of different physiologic monitoring
      modalities and combinations of modalities used during pediatric procedural
      sedation; to describe how physiologic monitoring varies among different classes
      of patients, health care providers (ie, ranging from anesthesiologists to
      emergency medicine physicians to nurse practitioners), procedures, and sedative
      medications employed; and to determine the proportion of sedations meeting
      published guidelines for physiologic monitoring. DESIGN This was a prospective,
      observational study from September 1, 2007, through March 31, 2011. SETTING: Data
      were collected in areas outside of the operating room, such as intensive care
      units, radiology, emergency departments, and clinics. PARTICIPANTS: Thirty-seven
      institutions comprise the Pediatric Sedation Research Consortium that
      prospectively collects data on procedural sedation/anesthesia performed outside
      of the operating room in all children up to age 21 years. MAIN OUTCOME MEASURES:
      Data including demographics, procedure performed, provider level, adverse events,
      medications, and physiologic monitors used are entered into a web-based system.
      RESULTS: Data from 114 855 subjects were collected and analyzed. The frequency of
      use of each physiologic monitoring modality by health care provider type,
      medication used, and procedure performed varied significantly. The largest
      difference in frequency of monitoring use was seen between providers using
      electrocardiography (13%-95%); the smallest overall differences were seen in
      monitoring use based on the American Society of Anesthesiologists classifications
      (1%-10%). Guidelines published by the American Academy of Pediatrics, the
      American College of Emergency Physicians, and the American Society of
      Anesthesiologists for nonanesthesiologists were adhered to for 52% of subjects.
      CONCLUSIONS: A large degree of variability exists in the use of physiologic
      monitoring modalities for pediatric procedural sedation. Differences in
      monitoring are evident between sedation providers, medications, procedures, and
      patient types.

PMID- 22965649
TI  - Financial implications of ventral hernia repair: a hospital cost analysis.
AB  - INTRODUCTION: Complicated ventral hernias are often referred to tertiary care
      centers. Hospital costs associated with these repairs include direct costs (mesh
      materials, supplies, and nonsurgeon labor costs) and indirect costs (facility
      fees, equipment depreciation, and unallocated labor). Operative supplies
      represent a significant component of direct costs, especially in an era of
      proprietary synthetic meshes and biologic grafts. We aim to evaluate the cost
      effectiveness of complex abdominal wall hernia repair at a tertiary care referral
      facility. METHODS: Cost data on all consecutive open ventral hernia repairs (CPT
      codes 49560, 49561, 49565, and 49566) performed between 1 July 2008 and 31 May
      2011 were analyzed. Cases were analyzed based upon hospital status (inpatient vs.
      outpatient) and whether the hernia repair was a primary or secondary procedure.
      We examined median net revenue, direct costs, contribution margin, indirect
      costs, and net profit/loss. Among primary hernia repairs, cost data were further
      analyzed based upon mesh utilization (no mesh, synthetic, or biologic). RESULTS:
      Four-hundred and fifteen patients underwent ventral hernia repair (353 inpatients
      and 62 outpatients); 173 inpatients underwent ventral hernia repair as the
      primary procedure; 180 inpatients underwent hernia repair as a secondary
      procedure. Median net revenue ($17,310 vs. 10,360, p < 0.001) and net losses
      (3,430 vs. 1,700, p < 0.025) were significantly greater for those who underwent
      hernia repair as a secondary procedure. Among inpatients undergoing ventral
      hernia repair as the primary procedure, 46 were repaired without mesh; 79 were
      repaired with synthetic mesh and 48 with biologic mesh. Median direct costs for
      cases performed without mesh were $5,432; median direct costs for those using
      synthetic and biologic mesh were $7,590 and 16,970, respectively (p < .01).
      Median net losses for repairs without mesh were $500. Median net profit of $60
      was observed for synthetic mesh-based repairs. The median contribution margin for
      cases utilizing biologic mesh was -$4,560, and the median net financial loss was
      $8,370. Outpatient ventral hernia repairs, with and without synthetic mesh,
      resulted in median net losses of $1,560 and 230, respectively. CONCLUSIONS:
      Ventral hernia repair is associated with overall financial losses. Inpatient
      synthetic mesh repairs are essentially budget neutral. Outpatient and inpatient
      repairs without mesh result in net financial losses. Inpatient biologic mesh
      repairs result in a negative contribution margin and striking net financial
      losses. Cost-effective strategies for managing ventral hernias in a tertiary care
      environment need to be developed in light of the financial implications of this
      patient population.

PMID- 22965650
TI  - Prior fundoplication does not improve safety or efficacy outcomes of
      radiofrequency ablation: results from the U.S. RFA Registry.
AB  - BACKGROUND: Ongoing gastroesophageal reflux may impair healing and re
      epithelialization after radiofrequency ablation (RFA) of Barrett's esophagus
      (BE). Because prior fundoplication may improve reflux control, our aim was to
      assess the relationship between prior fundoplication and the safety/efficacy of
      RFA. METHODS: We assessed the U.S. RFA Registry, a nationwide registry of BE
      patients receiving RFA at 148 institutions, to compare the safety and efficacy of
      ablation between those with prior fundoplication and those with medical
      management (proton pump inhibition). RESULTS: Among 5,537 patients receiving RFA,
      301 (5.4 %) had prior fundoplication. Of fundoplication subjects, 1.0 % developed
      stricture and 1.0 % were hospitalized after RFA. Rates of stricture, bleeding,
      and hospitalization were not statistically different (p = ns) between patients
      with and without prior fundoplication. Complete eradication of intestinal
      metaplasia and complete eradication of dysplasia were achieved in 71 % and 87 %
      of fundoplication patients, and 73 % and 87 % of patients without fundoplication,
      respectively (p = ns for both). Patients with prior fundoplication needed similar
      numbers of RFA sessions for eradication compared with those without
      fundoplication. CONCLUSIONS: Radiofrequency ablation, with or without prior
      fundoplication, is safe and effective in eradicating BE. Prior fundoplication was
      associated with similar adverse event and efficacy rates when compared with
      medical management.

PMID- 22965652
TI  - Religious/Spiritual Well-being, personality and mental health: a review of
      results and conceptual issues.
AB  - The current paper provides background to the development of the Multidimensional
      Inventory for Religious/Spiritual Well-being and then summarises findings derived
      from its use with other measures of health and personality. There is substantial
      evidence for religiosity/spirituality being positively related to a variety of
      indicators of mental health, including subjective well-being and personality
      dimensions. Furthermore, religiosity/spirituality can play an important role in
      the process of recovering from mental illness as well as providing a protective
      function against addictive or suicidal behaviours. However, further research is
      needed to examine the mechanisms through which religiosity/spirituality have an
      impact on health-related conditions. 

PMID- 22965651
TI  - Medication prescribing in frail older people.
AB  - PURPOSE: While some people remain fit and active as they grow older, others
      experience complex problems: disease, dependency and disability. Frailty is a
      term used to describe this latter group, capturing differences in health status
      among older people. Many frail older people have multiple chronic co-morbidities
      and functional impairments and, according to guidelines for the management of
      individual conditions, should be prescribed long lists of medications. However,
      older people (particularly those who are frail) are often excluded from drug
      trials, and treatment decisions are therefore based on evidence extrapolated from
      more robust patient groups with fewer physiological deficits. The risk of adverse
      drug reactions (ADRs) increases with increasing patient frailty, and polypharmacy
      has negative consequences above and beyond the risks of individual drugs.
      Increasing numbers of medications are associated with a higher likelihood of non
      adherence and a significantly greater risk of ADRs. Older people taking five or
      more medications are at higher risk of delirium and falls, independent of
      medication indications. METHODS: This is a short review of the different
      approaches to defining and measuring frailty. We summarise the factors
      contributing to ADRs in frail older people and describe the pharmacokinetic and
      pharmacodynamics changes associated with ageing and frailty. By considering goals
      of care for frail older people, we explore how the appropriateness of medication
      prescribing for older people could be improved. CONCLUSION: Since all physicians
      are likely to provide care for this group of vulnerable patients, understanding
      the concept of frailty may help to optimise medication prescribing for older
      people. The incorporation of frailty measures into future clinical studies of
      drug effects and pharmacokinetics is important if we are to improve medication
      use and guide drug doses for fit and frail older people.

PMID- 22965653
TI  - Coverage theories for metagenomic DNA sequencing based on a generalization of
      Stevens' theorem.
AB  - Metagenomic project design has relied variously upon speculation, semi-empirical
      and ad hoc heuristic models, and elementary extensions of single-sample Lander
      Waterman expectation theory, all of which are demonstrably inadequate. Here, we
      propose an approach based upon a generalization of Stevens' Theorem for randomly
      covering a domain. We extend this result to account for the presence of multiple
      species, from which are derived useful probabilities for fully recovering a
      particular target microbe of interest and for average contig length. These show
      improved specificities compared to older measures and recommend deeper data
      generation than the levels chosen by some early studies, supporting the view that
      poor assemblies were due at least somewhat to insufficient data. We assess
      predictions empirically by generating roughly 4.5 Gb of sequence from a twelve
      member bacterial community, comparing coverage for two particular members,
      Selenomonas artemidis and Enterococcus faecium, which are the least ([Formula:
      see text]3 %) and most ([Formula: see text]12 %) abundant species, respectively.
      Agreement is reasonable, with differences likely attributable to coverage biases.
      We show that, in some cases, bias is simple in the sense that a small reduction
      in read length to simulate less efficient covering brings data and theory into
      essentially complete accord. Finally, we describe two applications of the theory.
      One plots coverage probability over the relevant parameter space, constructing
      essentially a "metagenomic design map" to enable straightforward analysis and
      design of future projects. The other gives an overview of the data requirements
      for various types of sequencing milestones, including a desired number of contact
      reads and contig length, for detection of a rare viral species. 

PMID- 22965654
TI  - A novel approach to probabilistic biomarker-based classification using functional
      near-infrared spectroscopy.
AB  - Pattern recognition approaches to the analysis of neuroimaging data have brought
      new applications such as the classification of patients and healthy controls
      within reach. In our view, the reliance on expensive neuroimaging techniques
      which are not well tolerated by many patient groups and the inability of most
      current biomarker algorithms to accommodate information about prior class
      frequencies (such as a disorder's prevalence in the general population) are key
      factors limiting practical application. To overcome both limitations, we propose
      a probabilistic pattern recognition approach based on cheap and easy-to-use multi
      channel near-infrared spectroscopy (fNIRS) measurements. We show the validity of
      our method by applying it to data from healthy controls (n = 14) enabling
      differentiation between the conditions of a visual checkerboard task. Second, we
      show that high-accuracy single subject classification of patients with
      schizophrenia (n = 40) and healthy controls (n = 40) is possible based on
      temporal patterns of fNIRS data measured during a working memory task. For
      classification, we integrate spatial and temporal information at each channel to
      estimate overall classification accuracy. This yields an overall accuracy of 76%
      which is comparable to the highest ever achieved in biomarker-based
      classification of patients with schizophrenia. In summary, the proposed algorithm
      in combination with fNIRS measurements enables the analysis of sub-second,
      multivariate temporal patterns of BOLD responses and high-accuracy predictions
      based on low-cost, easy-to-use fNIRS patterns. In addition, our approach can
      easily compensate for variable class priors, which is highly advantageous in
      making predictions in a wide range of clinical neuroimaging applications.

PMID- 22965655
TI  - Intima-medial thickness homogeneity in the common carotid artery: measurement
      method and preliminary clinical study.
AB  - BACKGROUND: To propose and test in a preliminary clinical study a novel method
      for calculating intima-medial thickness (IMT) homogeneity (IMTH). METHODS: IMT
      was measured off-line on every horizontal pixel line along the far wall of the
      common carotid artery, with previously validated software. IMTH was assessed by
      the SD, coefficient of variation, and interval distribution of obtained IMT
      values. This method was applied to 129 individuals (age, 40-60 years), including
      49 healthy control subjects, 44 subjects at high risk of atherosclerosis, and 36
      subjects with known atherosclerosis. Differences with a p value <0.05 were
      considered statistically significant. RESULTS: SD and coefficient of variation
      were higher in the high-risk than in the control group, as well as in high-risk
      and control subgroups with maximal IMT = 0.8 mm or mean IMT = 0.55-0.65 mm. There
      were 85.7, 62.8, and 36% of IMT values in the 0.4- to 0.6-mm range and 0.89,
      13.8, and 21.2% of IMT values in the 0.8- to 1.2-mm range in the control, high
      risk, and atherosclerosis groups, respectively. CONCLUSIONS: IMTH is a promising
      approach for the assessment of atherosclerosis, in addition to conventional IMT
      measurement. Further clinical studies are needed to assess its clinical
      usefulness.

PMID- 22965656
TI  - Population-based case-control study of recreational drug use and testis cancer
      risk confirms an association between marijuana use and nonseminoma risk.
AB  - BACKGROUND: Testicular germ cell tumor (TGCT) incidence increased steadily in
      recent decades, but causes remain elusive. Germ cell function may be influenced
      by cannabinoids, and 2 prior epidemiologic studies reported that the use of
      marijuana may be associated with nonseminomatous TGCT. Here, the authors evaluate
      the relation between TGCTs and exposure to marijuana and other recreational drugs
      using a population-based case-control study. METHODS: In total, 163 patients who
      were diagnosed with TGCT in Los Angeles County from December 1986 to April 1991
      were enrolled, and 292 controls were matched on age, race/ethnicity, and
      neighborhood. Participants were asked about drug use by a structured, in-person
      interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated
      using conditional logistic regression analysis adjusted for history of
      cryptorchidism; education; religiosity; and reported use of marijuana, cocaine,
      and amyl nitrite. RESULTS: Compared with never use, ever use of marijuana had a 2
      fold increased risk (OR, 1.94; 95% CI, 1.02-3.68), whereas ever use of cocaine
      had a negative association with TGCT (OR, 0.54; 95% CI, 0.32-0.91).
      Stratification on tumor histology revealed a specific association of marijuana
      use with nonseminoma and mixed histology tumors (OR, 2.42; 95% CI, 1.08-5.42).
      CONCLUSIONS: A specific association was observed between marijuana use and the
      risk of nonseminoma and mixed tumors. To the authors' knowledge, this is the
      first report of a negative association between cocaine use and TGCT risk. The
      current results warrant mechanistic studies of marijuana's effect on the
      endocannabinoid system and TGCT risk and caution that recreational and
      therapeutic use of cannabinoids by young men may confer malignant potential to
      testicular germ cells.

PMID- 22965657
TI  - Treatment satisfaction and improvement in health-related quality of life with
      onabotulinumtoxinA in patients with urinary incontinence due to neurogenic
      detrusor overactivity.
AB  - AIMS: OnabotulinumtoxinA significantly reduces urinary incontinence (UI) and
      improves bladder management in patients with neurogenic detrusor overactivity
      (NDO). We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes
      (PROs) in patients with UI due to NDO in a double-blind, placebo-controlled
      study. METHODS: Patients with UI due to NDO (from multiple sclerosis or spinal
      cord injury) were randomized to intradetrusor placebo (n = 92) or
      onabotulinumtoxinA 200 U (n = 92) or 300 U (n = 91). PROs included Incontinence
      Quality of Life (I-QOL) Questionnaire to assess health-related quality of life
      (HRQoL), the 16-item modified Overactive Bladder-Patient Satisfaction with
      Treatment Questionnaire (OAB-PSTQ) to assess treatment satisfaction, and Patient
      Global Assessment to assess treatment goal achievement. RESULTS: Mean improvement
      in I-QOL total score at weeks 6 and 12 was significantly greater with both
      onabotulinumtoxinA 200 U and 300 U versus placebo (Delta12.3 for 200 U and
      Delta14.9 for 300 U vs. placebo; P < 0.001), and was clinically meaningful. For
      those patients who completed the OAB-PSTQ, improvement in satisfaction at weeks 6
      and 12 was significantly greater for onabotulinumtoxinA versus placebo (P <
      0.001, all comparisons). At 6 weeks, greater proportions of onabotulinumtoxinA
      treated patients than placebo reported being somewhat or very satisfied (200 U,
      77.5% and 300 U, 67.8% vs. placebo, 39.5%), and significant progress toward or
      complete achievement of primary treatment goal (200 U, 62.9% and 300 U, 61.6% vs.
      placebo, 16.5%). CONCLUSIONS: NDO patients treated with onabotulinumtoxinA 200 or
      300 U had significantly greater improvement in HRQoL and greater treatment
      satisfaction compared with placebo-treated patients, with no clinically relevant
      differences between onabotulinumtoxinA doses.

PMID- 22965658
TI  - Metabolic and proteomic adaptation of Lactobacillus rhamnosus strains during
      growth under cheese-like environmental conditions compared to de Man, Rogosa, and
      Sharpe medium.
AB  - The aim of this study was to demonstrate the metabolic and proteomic adaptation
      of Lactobacillus rhamnosus strains, which were isolated at different stages of
      Parmigiano Reggiano cheese ripening. Compared to de Man, Rogosa, and Sharpe (MRS)
      broth, cultivation under cheese-like conditions (cheese broth, CB) increased the
      number of free amino acids used as carbon sources. Compared with growth on MRS or
      pasteurized and microfiltrated milk, all strains cultivated in CB showed a low
      synthesis of d,l-lactic acid and elevated levels of acetic acid. The proteomic
      maps of the five representative strains, showing different metabolic traits, were
      comparatively determined after growth on MRS and CB media. The amount of
      intracellular and cell-associated proteins was affected by culture conditions and
      diversity between strains, depending on their time of isolation. Protein spots
      showing decreased (62 spots) or increased (59 spot) amounts during growth on CB
      were identified using MALDI-TOF-MS/MS or LC-nano-ESI-MS/MS. Compared with
      cultivation on MRS broth, the L. rhamnosus strains cultivated under cheese-like
      conditions had modified amounts of some proteins responsible for protein
      biosynthesis, nucleotide, and carbohydrate metabolisms, the glycolysis pathway,
      proteolytic activity, cell wall, and exopolysaccharide biosynthesis, cell
      regulation, amino acid, and citrate metabolism, oxidation/reduction processes,
      and stress responses.

PMID- 22965659
TI  - Facile access to silicon-functionalized bis-silylene titanium(II) complexes.
AB  - A series of unprecedented bis-silylene titanium(II) complexes of the type
      [(eta(5)-C(5)H(5))(2)Ti(LSiX)(2)] (L=PhC(NtBu)(2); X=Cl, CH(3), H) has been
      prepared using a phosphane elimination strategy. Treatment of the [(eta(5)
      C(5)H(5))(2)Ti(PMe(3))(2)] precursor (1) with two molar equivalents of the N
      heterocyclic chlorosilylene LSiCl (2), results in [(eta(5)
      C(5)H(5))(2)Ti(LSiCl)(2)] (3) with concomitant PMe(3) elimination. The presence
      of a Si-Cl bond in 3 enabled further functionalization at the silicon(II) center.
      Accordingly, a salt metathesis reaction of 3 with two equivalents of MeLi results
      in [(eta(5)-C(5)H(5))(2)Ti(LSiMe)(2)] (4). Similarly, the reaction of 3 with two
      equivalents of LiBHEt(3) results in [(eta(5)-C(5)H(5))(2)Ti(LSiH)(2)] (5), which
      represents the first example of a bis-(hydridosilylene) metal complex. All
      complexes were fully characterized and the structures of 3 and 4 elucidated by
      single-crystal X-ray diffraction analysis. DFT calculations of complexes 3-5 were
      also carried out to assess the nature of the titanium-silicon bonds. Two sigma
      and one pi-type molecular orbital, delocalized over the Si-Ti-Si framework, are
      observed.

PMID- 22965660
TI  - Evaluation of the performance characteristics of bilayer tablets: Part II. Impact
      of environmental conditions on the strength of bilayer tablets.
AB  - Ambient air humidity and temperature are known to influence the mechanical
      strength of tablets. The objective of this work is to understand the influence of
      processing parameters and environmental conditions (humidity and temperature) on
      the strength of bilayer tablets. As part of this study, bilayer tablets were
      compressed with different layer ratios, dwell times, layer sequences, material
      properties (plastic and brittle), first and second layer forces, and lubricant
      concentrations. Compressed tablets were stored in stability chambers controlled
      at predetermined conditions (40C/45%RH, 40C/75%RH) for 1, 3, and 5 days. The
      axial strength of the stored tablets was measured and a statistical model was
      developed to determine the effects of the aforementioned factors on the strength
      of bilayer tablets. As part of this endeavor, a full 3 * 2(4) factorial design
      was executed. Responses of the experiments were analyzed using PROC GLM of SAS
      (SAS Institute Inc, Cary, North Carolina, USA). A model was fit using all the
      responses to determine the significant interactions (p < 0.05). Results of this
      study indicated that storage conditions and storage time have significant impact
      on the strength of bilayer tablets. For Avicel-lactose and lactose-Avicel
      tablets, tablet strength decreased with the increasing humidity and storage time.
      But for lactose-lactose tablets, due to the formation of solid bridges upon
      storage, an increase in tablet strength was observed. Significant interactions
      were observed between processing parameters and storage conditions on the
      strength of bilayer tablets.

PMID- 22965661
TI  - Product development studies on surface-adsorbed nanoemulsion of olmesartan
      medoxomil as a capsular dosage form.
AB  - The present study aimed at development of capsular dosage form of surface
      adsorbed nanoemulsion (NE) of olmesartan medoxomil (OLM) so as to overcome the
      limitations associated with handling of liquid NEs without affecting their
      pharmaceutical efficacy. Selection of oil, surfactant, and cosurfactant for
      construction of pseudoternary phase diagrams was made on the basis of solubility
      of drug in these excipients. Rationally selected NE formulations were evaluated
      for percentage transmittance, viscosity, refractive index, globule size, zeta
      potential, and polydispersity index (PDI). Formulation (F3) comprising of Capmul
      MCM(r) (10% v/v), Tween 80(r) (11.25% v/v), polyethylene glycol 400 (3.75% v/v),
      and double-distilled water (75% v/v) displayed highest percentage cumulative drug
      release (%CDR; 96.69 +/- 1.841), least globule size (17.51 +/- 5.87 nm), low PDI
      (0.203 +/- 0.032), high zeta potential (-58.93 +/- 0.98 mV), and hence was
      selected as the optimized formulation. F3 was adsorbed over colloidal silicon
      dioxide (2 ml/400 mg) to produce free-flowing solid surface-adsorbed NE that
      presented a ready-to-fill capsule composition. Conversion of NE to surface
      adsorbed NE and its reconstitution to NE did not affect the in vitro release
      profile of OLM as the similarity factor with respect to NE was found to be 66%
      and 73% respectively. The %CDR after 12 h for optimized NE, surface-adsorbed NE,
      and reconstituted NE was found to be 96.69 +/- 0.54, 96.07 +/- 1.76, and 94.78 +/
      1.57, respectively (p > 0.05). The present study established capsulated surface
      adsorbed NE as a viable delivery system with the potential to overcome the
      handling limitations of NE.

PMID- 22965662
TI  - Preparation and evaluation of sustained-release matrix tablets based on
      metoprolol and an acrylic carrier using injection moulding.
AB  - Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by
      injection moulding. The influence of process temperature; matrix composition;
      drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT),
      fumarate (MPF) and succinate (MPS) on ease of processing and drug release were
      evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest
      drug release, substituting part of Eudragit RL by RS resulted in slower drug
      release, all following first-order release kinetics. Drug load only affected drug
      release of matrices composed of Eudragit RS: a higher MPT concentration yielded
      faster release rates. Adding triethyl citrate enhanced the processability, but
      was detrimental to long-term stability. The process temperature and plasticizer
      level had no effect on drug release, whereas metoprolol salt form significantly
      influenced release properties. The moulded tablets had a low porosity and a
      smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit
      RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment,
      thermal analysis and X-ray diffraction demonstrated the formation of a solid
      solution immediately after production, in which H-bonds were formed between
      metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high
      drug loadings of MPS and MPF showed a tendency to recrystallise during storage.
      The in vivo performance of injection-moulded tablets was strongly dependent upon
      drug loading.

PMID- 22965663
TI  - Inhibition of transcription by platinated triplex-forming oligonucleotides.
AB  - Platinated triplex-forming oligonucleotides (TFOs) consisting of 2'
      methoxythymidine and 2'-methoxy-5-methylcytidine and an N-7 platinated
      deoxyguanosine ((Pt)G) at the 5'-((Pt)G-TFO), 3'-(TFO-G(Pt)), or 3'- and 5'
      ((Pt)G-TFO-G(Pt)) ends of the TFO form mono-((Pt)G-TFO and TFO-G(Pt)) and
      interstrand ((Pt)G-TFO-G(Pt)) cross-links with target DNA as a result of reaction
      of the (Pt)G with guanines adjacent to the homopurine TFO binding site in the
      target. The extent of cross-linking is greatest when the (Pt)G is located on the
      3' end of the TFO and the target guanine is on the same strand as the TFO binding
      site. Multiple, contiguous deoxyguanosines in the TFO binding site or a cytosine
      adjacent to the G(Pt) of the TFO significantly reduce cross-linking. DNA reporter
      plasmids in which platinated TFOs were cross-linked at a site in the transcribed
      region between a CMV promoter and a luciferase reporter gene were transfected
      into Chinese hamster ovary cells, and luciferase expression was compared with
      that for the corresponding non-cross-linked plasmid. Luciferase expression was
      inhibited 95 % when TFO-G(Pt) was bound and cross-linked to the transcribed
      strand, demonstrating that the cross-linked TFO was able to block transcription
      elongation. Further inhibition (99 %) was observed in nucleotide excision repair
      (NER) deficient cells, suggesting that NER may repair this lesion. The 3'-G(Pt)
      group of TFO-G(Pt) protects the TFO from degradation by exonucleases found in
      mammalian serum. Taken together, these results suggest that platinated TFOs of
      the type TFO-G(Pt) may find applications as agents for suppressing DNA
      transcription and consequently inhibiting gene expression in mammalian cells.

PMID- 22965665
TI  - Selective pyrophosphate recognition by cyclic peptide receptors in physiological
      saline.
AB  - The anion binding ability of a family of bis(Zn(II)-Dpa) functionalized cyclic
      peptides has been investigated using displacement assays with a fluorescent
      coumarin indicator in water, saline solution, and Krebs buffer. Non-binding side
      chain steric bulk, the relative position of binding sites, and the scaffold size
      were all found to affect the ability of these receptors to discriminate between
      polyphosphate ions. Most receptors showed some selectivity for pyrophosphate over
      ATP and ADP in water and saline, and this selectivity was significantly enhanced
      in the biologically relevant Krebs buffer giving chemosensing ensembles capable
      of selective recognition of pyrophosphate in the presence of excess ATP.

PMID- 22965664
TI  - Beyond Gomez-Lopez-Hernandez syndrome: recurring phenotypic themes in
      rhombencephalosynapsis.
AB  - Rhombencephalosynapsis (RES) is an uncommon cerebellar malformation characterized
      by fusion of the hemispheres without an intervening vermis. Frequently described
      in association with Gomez-Lopez-Hernandez syndrome, RES also occurs in
      conjunction with VACTERL features and with holoprosencephaly (HPE). We sought to
      determine the full phenotypic spectrum of RES in a large cohort of patients.
      Information was obtained through database review, patient questionnaire,
      radiographic, and morphologic assessment, and statistical analysis. We assessed
      53 patients. Thirty-three had alopecia, 3 had trigeminal anesthesia, 14 had
      VACTERL features, and 2 had HPE with aventriculy. Specific craniofacial features
      were seen throughout the cohort, but were more common in patients with alopecia.
      We noted substantial overlap between groups. We conclude that although some
      distinct subgroups can be delineated, the overlapping features seen in our cohort
      suggest an underlying spectrum of RES-associated malformations rather than a
      collection of discrete syndromes.

PMID- 22965666
TI  - Unanticipated reversal of polarity in primary human mammospheres cultured in
      ultra-low attachment plates.

PMID- 22965668
TI  - In response to Late complications of nickel-titanium alloy stent in tracheal
      stenosis.

PMID- 22965667
TI  - A chemically programmed antibody is a long-lasting and potent inhibitor of
      influenza neuraminidase.
AB  - Programming an anti-flu strategy: A new and potent neuraminidase inhibitor that
      maintains long-term systemic exposure of an antibody and the therapeutic activity
      of the neuraminadase inhibitor zanamivir has been created. This strategy could
      provide a promising new class of influenza A drugs for therapy and prophylaxis,
      and validates enzyme inhibitors as programming agents in synthetic immunology.

PMID- 22965669
TI  - Multivariate pattern analysis reveals subtle brain anomalies relevant to the
      cognitive phenotype in neurofibromatosis type 1.
AB  - Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with
      cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits
      is not well understood. Abnormal brain structure, including increased total brain
      volume, white matter (WM) and grey matter (GM) abnormalities have been reported
      in the NF1 brain. These previous studies employed univariate model-driven methods
      preventing detection of subtle and spatially distributed differences in brain
      anatomy. Multivariate pattern analysis allows the combination of information from
      multiple spatial locations yielding a discriminative power beyond that of single
      voxels. Here we investigated for the first time subtle anomalies in the NF1
      brain, using a multivariate data-driven classification approach. We used support
      vector machines (SVM) to classify whole-brain GM and WM segments of structural T1
      -weighted MRI scans from 39 participants with NF1 and 60 non-affected
      individuals, divided in children/adolescents and adults groups. We also employed
      voxel-based morphometry (VBM) as a univariate gold standard to study brain
      structural differences. SVM classifiers correctly classified 94% of cases
      (sensitivity 92%; specificity 96%) revealing the existence of brain structural
      anomalies that discriminate NF1 individuals from controls. Accordingly, VBM
      analysis revealed structural differences in agreement with the SVM weight maps
      representing the most relevant brain regions for group discrimination. These
      included the hippocampus, basal ganglia, thalamus, and visual cortex. This
      multivariate data-driven analysis thus identified subtle anomalies in brain
      structure in the absence of visible pathology. Our results provide further
      insight into the neuroanatomical correlates of known features of the cognitive
      phenotype of NF1.

PMID- 22965670
TI  - ACE inhibitors versus ARBs versus DRIs: a systematic update.

PMID- 22965672
TI  - Tocilizumab for giant cell arteritis: an amazing result.
AB  - Giant cell arteritis (GCA), previously Horton's disease, is a systemic vasculitis
      affecting the middle-sized or large arteries in patients older than 50 years of
      age. The mainstay of the treatment of GCA is glucocorticoid therapy. Herein, we
      present a case with giant cell arteritis resistant to oral and intravenous
      steroid, intravenous cyclophosphamide and mycophenolate mofetil, but successfully
      treated with tocilizumab.

PMID- 22965673
TI  - Is the prevalence of arterial hypertension in rheumatoid arthritis and
      osteoarthritis associated with disease?
AB  - In this study, we compare the prevalence of arterial hypertension (HT) in
      rheumatoid arthritis (RA) and osteoarthritis (OA) patients, exposed to high- and
      low-grade chronic inflammation, respectively, to assess the possible association
      between chronic inflammation and HT. A total of consecutive 627 RA and 352 OA
      patients were enrolled in this multicentric study. HT was defined as a systolic
      blood pressure (BP) >= 140 and/or diastolic BP >= 90 mmHg or current use of any
      antihypertensive drug. Overweight/obesity was defined as body mass index (BMI) >=
      25, and patients >=65 years were considered elderly. The prevalence of HT was
      higher in the OA group than in the RA group [73.3 % (95 % CI, 68.4, 77.7) and
      59.5 % (95 % CI, 55.6, 68.4) P < 0.001, respectively]. When the results were
      adjusted for age and BMI, the HT prevalence was similar in both groups [RA 59 %
      (95 % CI, 55.1, 63.8) OA 60 % (95 % CI, 58.4, 65.0)]. In both groups, the
      prevalence of HT was higher in the elderly and those who were overweight than in
      the younger patients and those with a BMI < 25. Overweight (BMI >= 25) and age
      >=65 were independent predictors of HT in multivariate logistic regression model,
      which showed no association between HT and the disease (RA or OA). The results
      indicate a robust association of age and BMI with HT prevalence in both RA and
      OA. The difference in HT prevalence between RA and OA is due rather to age and
      BMI than to the features of the disease, putting into question specific
      association of HT with RA.

PMID- 22965674
TI  - Heavy alcohol intake and intracerebral hemorrhage: characteristics and effect on
      outcome.
AB  - OBJECTIVES: To identify associated factors and influence on long-term outcome of
      heavy alcohol intake in a large prospective cohort of consecutive patients with a
      spontaneous intracerebral hemorrhage (ICH). METHODS: Between November 2004 and
      March 2009, we prospectively recruited 562 consecutive adults with a spontaneous
      ICH. We excluded patients without information on drinking habit (n = 22). Heavy
      alcohol intake was defined as a regular consumption of more than 300 g
      alcohol/week. We performed bivariate and multivariate analyses (logistic
      regression) based on demographic and radiologic models. Survival analyses were
      performed using Kaplan-Meier statistics. RESULTS: Among 540 patients with ICH,
      137 (25) were heavy alcohol drinkers (median age 60 vs 74 years in nonabusers; p
      < 0.0001). In the multivariate demographic model, heavy alcohol drinkers were
      less likely to be older (odds ratio [OR] 0.97 per 1-year increase, 95% confidence
      interval [CI] 0.95-0.98) and to have a history of ischemic heart disease (OR
      0.34, 95% CI 0.15-0.77) and more likely to be smokers (OR 3.96, 95% CI 2.43
      6.46). In the radiologic model, independent factors were nonlobar location of ICH
      (OR 1.71, 95% CI 1.05-2.77) and less severe leukoaraiosis (OR 0.76 per 1-step
      increase, 95%CI 0.62-0.73). Platelet counts and prothrombin ratio were
      significantly lower among heavy alcohol drinkers (respectively, p = 0.01 and p =
      0.017). Heavy alcohol intake was predictive of 2 years mortality only among
      patients younger than 60 years with nonlobar ICH (hazard ratio 1.96, 95% CI 1.06
      3.63). CONCLUSION: Heavy alcohol intake is associated with the occurrence of ICH
      at a young age. However, the underlying vasculopathy remains unexplored in these
      patients. Indirect markers suggest small-vessel disease at an early stage that
      might be enhanced by moderate hemostatic disorders.

PMID- 22965675
TI  - Associations of welding and manganese exposure with Parkinson disease: review and
      meta-analysis.
AB  - OBJECTIVE: To examine associations of welding and manganese exposure with
      Parkinson disease (PD) using meta-analyses of data from cohort, case-control, and
      mortality studies. METHODS: Epidemiologic studies related to welding or manganese
      exposure and PD were identified in a PubMed search, article references, published
      reviews, and abstracts. Inclusion criteria were 1) cohort, case-control, or
      mortality study with relative risk (RR), odds ratio (OR), or mortality OR (MOR)
      and 95 confidence intervals (95% CI); 2) RR, OR, and MOR matched or adjusted for
      age and sex; 3) valid study design and analysis. When participants of a study
      were a subgroup of those in a larger study, only results of the larger study were
      included to assure independence of datasets. Pooled RR/OR estimates and 95% CIs
      were obtained using random effects models; heterogeneity of study effects were
      evaluated using the Q statistic and I(2) index in fixed effect models. RESULTS:
      Thirteen studies met inclusion criteria for the welding meta-analysis and 3
      studies for the manganese exposure meta-analysis. The pooled RR for the
      association between welding and PD for all study designs was 0.86 (95% CI 0.80
      0.92), with absence of between-study heterogeneity (I(2) = 0.0). Effect measures
      for cohort, case-control, and mortality studies were similar (0.91, 0.82, 0.87).
      For the association between manganese exposure and PD, the pooled OR was 0.76
      (95% CI 0.41-1.42). CONCLUSIONS: Welding and manganese exposure are not
      associated with increased PD risk. Possible explanations for the inverse
      association between welding and PD include confounding by smoking, healthy worker
      effect, and hormesis.

PMID- 22965676
TI  - Extrusion of stent graft from the carotid artery: a major pain in the neck.

PMID- 22965677
TI  - Pearls & oy-sters: ocular ischemic syndrome.

PMID- 22965678
TI  - Right brain: a descriptive account of two patients' experience with and
      adaptations to Balint syndrome.

PMID- 22965679
TI  - Teaching video neuroimages: acute Adie syndrome.

PMID- 22965680
TI  - An additive-multiplicative rates model for recurrent event data with informative
      terminal event.
AB  - In this article, we propose an additive-multiplicative rates model for recurrent
      event data in the presence of a terminal event such as death. The association
      between recurrent and terminal events is nonparametric. For inference on the
      model parameters, estimating equation approaches are developed, and the
      asymptotic properties of the resulting estimators are established. The finite
      sample behavior of the proposed estimators is evaluated through simulation
      studies, and an application to a bladder cancer study is provided.

PMID- 22965681
TI  - Avidity of influenza-specific memory CD8+ T-cell populations decays over time
      compromising antiviral immunity.
AB  - Decline of cell-mediated immunity is often attributed to decaying T-cell numbers
      and their distribution in peripheral organs. This study examined the hypothesis
      that qualitative as well as quantitative changes contribute to the declining
      efficacy of CD8(+)  T-cell memory. Using a model of influenza virus infection,
      where loss of protective CD8(+)  T-cell immunity was observed 6 months
      postinfection, we found no decline in antigen-specific T-cell numbers or
      migration to the site of secondary infection. There was, however, a large
      reduction in antigen-specific CD8(+)  T-cell degranulation, cytokine secretion,
      and polyfunctionality. A profound loss of high-avidity T cells over time
      indicated that failure to confer protective immunity resulted from the inferior
      functional capacity of remaining low avidity cells. These data imply that high
      avidity central memory T cells wane with declining antigen levels, leaving lower
      avidity T cells with reduced functional capabilities.

PMID- 22965682
TI  - Physical activity intensity and cardiometabolic risk in youth.
AB  - OBJECTIVE: To determine the association between physical activity (PA)
      intensities and cardiometabolic risk factors in youth. DESIGN: Cross-sectional
      study using data from the 2008 Healthy Hearts Prospective Cohort Study of
      Physical Activity and Cardiometabolic Health in Youth. SETTING: Rural and urban
      communities in Alberta, Canada. PARTICIPANTS: A convenience sample of 605 youth
      aged 9 to 17 years. Youth were on average aged 12.1 years, 248 were boys (41%),
      and 157 were overweight or obese (26%). MAIN EXPOSURE: Actical accelerometer
      measured PA intensity. MAIN OUTCOMES MEASURES: The primary outcome was body mass
      index (calculated as weight in kilograms divided by height in meters squared) z
      score. Secondary outcome measures included waist circumference, systolic blood
      pressure, and cardiorespiratory fitness (maximal oxygen consumption
      [[Vdot]O2max]). RESULTS: Body mass index z score, waist circumference, and
      systolic blood pressure decreased and [Vdot]O2max increased in a dose-response
      manner across tertiles of vigorous PA (adjusted P < .001). No significant
      differences in cardiometabolic risk factors were seen across tertiles of moderate
      or light PA in multivariable analyses. Achieving more than 7 minutes of vigorous
      PA daily was associated with a reduced adjusted odds ratio of overweight status
      (0.56; 95% CI, 0.33-0.95) and elevated systolic blood pressure (0.36; 95% CI,
      0.16-0.79). The odds of overweight status and elevated blood pressure decreased
      with increasing time and intensity of PA. CONCLUSIONS: Only vigorous PA was
      consistently associated with lower levels of waist circumference, body mass index
      z score, systolic blood pressure, and increased cardiorespiratory fitness in
      youth. These findings underscore the importance of vigorous PA in guidelines for
      children and adolescents.

PMID- 22965683
TI  - MS-based ligand binding assays with speed, sensitivity, and specificity.
AB  - Immunoassays are widely used in biochemical/clinical laboratories owing to their
      simplicity, speed, and sensitivity. We combined self-assembled monolayer-based
      immunoassays with MALDI-TOF MS to show that high-fidelity surface preparations
      with a novel matrix deposition/crystallization technique permits quantitative
      analysis of monolayer-bound antigens at picomolar detection limits. Calibration
      curves for intact proteins are possible over a broad concentration range and
      improved specificity of MS-immunoassays is highlighted by simultaneous label-free
      quantitation of ligand-bound protein complexes.

PMID- 22965684
TI  - Interstitial 3p25.3-p26.1 deletion in a patient with intellectual disability.
AB  - Interstitial deletions of the short arm of chromosome 3 are rare. We report on a
      3-year-old girl with intellectual disability, muscular hypotonia, strabismus, and
      facial anomalies in whom an interstitial 1.24 Mb deletion in 3p25.3-p26.1 was
      detected by SNP array analysis. The deleted region harbors 11 RefSeq genes
      including CAV3 and SRGAP3/MEGAP, which had been associated with muscle disorders
      and intellectual disability, respectively. The deletion overlaps with a slightly
      larger deletion in a girl with a more complex phenotype including congenital
      heart defect and epilepsy, which indicates that haploinsufficiency of one or
      several of the genes in the deleted interval causes intellectual deficits, but
      not heart defects or epilepsy. Thus, the patient broadens our knowledge of the
      phenotypic consequences of deletions in 3p25.3-p26.1 and facilitates genotype
      phenotype correlations for chromosome aberrations of this region.

PMID- 22965685
TI  - Copper-catalyzed nucleophilic trifluoromethylation of allylic halides: a simple
      approach to allylic trifluoromethylation.

PMID- 22965686
TI  - Differences in urodynamic study variables in adult patients with neurogenic
      bladder and myelomeningocele before and after augmentation enterocystoplasty.
AB  - AIMS: To evaluate urodynamic parameters in myelomeningocele patients with native
      bladders and after augmentation, continence rates and check the longevity of
      these parameters after lower urinary tract (LUT) reconstruction. METHODS: A
      retrospective review of adult myelomeningocele patients with UDS. RESULTS: 118
      adult patients with NGB secondary to myelomeningocele were identified. 58/118
      (49.1%) had UDS performed in our clinic: 18/58 (31%) after prior reconstruction
      ("Augment" group) and 40/58 (69%) during annual urologic follow up ("NoSx"
      group). Urodyanmic findings after augmentation included: Pdet@MCC 31.1 (1-95)
      cmH(2)O, MCC 495.9 ml, NDO in 3/18 (16.7%), mean DLPP 54.0 (48-60) cmH(2)O and
      mean ALPP 39.6 (20-110) cmH(2)O in 5/18 with an incompetent sphincter. Patients
      in "NoSx" group had the following findings: Pdet@MCC of 39.6 (1-60) cmH(2)O, MCC
      407.5 ml, 18/40 (45%) had NDO, mean DLPP of 48.1 (15-95) cmH(2)O and mean ALPP =
      51 (17-78) cmH(2)O in 10/40 with incompetent sphincter. In the "NoSx" group,
      19/40 (47.5%) had normal bladder compliance. Mean time from the surgery to UDS
      was 10.4 years. Continent patients in the "NoSx" group had a significantly higher
      MCC than incontinent patients in the same group (475 vs. 352 ml, P = 0.029). 8/17
      (47.1%) continent patients in "NoSx" group had normal UDS. CONCLUSIONS: Most
      patients after augmentation maintain low bladder pressures for more than 10
      years. Close long-term follow up should be maintained, especially in those
      patients that have not had prior augmentation. Urinary incontinence may be
      secondary to poor sphincteric function in patients with and without prior
      augmentation. Moreover, we should continue to follow patients after
      reconstruction as elevated detrusor pressures can still be seen. Strict follow up
      after LUT reconstruction still continues to be important.

PMID- 22965688
TI  - Theoretical studies of the asymmetric binary-acid-catalyzed tert-aminocyclization
      reaction: origins of the C(sp 3)-H activation and stereoselectivity.
AB  - A mechanistic study of the tert-aminocyclization reaction was performed by using
      DFT calculations and labeling experiments. The results showed that the reaction
      proceeded through a rate-limiting-, stereospecific-, and suprafacial 1,5-H
      transfer pathway, followed by a barrier-less C-C bond formation. The mode of
      stereocontrol for facial selection could be ruled out owing to the high
      activation energy of C-N bond rotation. The intrinsic feature of this Lewis acid
      activation was found to be the activation of the LUMO, as well as an intermediate
      stabilization effect. The catalytically active species was believed to be a 1:1
      complex of phosphoric acid and MgCl(2), which was stabilized by a H???Cl hydrogen
      bond. The chiral catalytic complex selectively recognizes and activates one of
      the two helical conformations of substrate A, required for 1,5-suprafacial H
      transfer, which dictates the stereoselectivity of the forming products.

PMID- 22965687
TI  - High ADAM8 expression is associated with poor prognosis in patients with
      hepatocellular carcinoma.
AB  - In this study,we investigated the ADAM8 expression in hepatocellular carcinoma
      (HCC) and its correlation with clinicopathologic features,including the survival
      of patients with HCC. Furthermore,we examined the biological processes regulated
      by ADAM8 during the development of using HepG2 cell line as a model system. We
      used immunohistochemistry to compare ADAM8 protein expression in HCC and normal
      liver tissues and further analyze the ADAM8 protein expression in
      clinicopathologically characterized 105 HCC cases.We stably knocked down the
      endogenous expression level of ADAM8 in HepG2 cells with specific shRNA
      expressing lentiviral vector. Following the successful establishment of stable
      cells,we examined in vitro cell growth by MTT assay,anchorage-independent growth
      by soft-agar colony formation assay and cell migration/invasion by transwell and
      boyden chamber assay. And in addition,we also investigated the in vivo tumor
      growth by xenograft transplantation of HepG2 cells into nude mice. Protein
      expression level of ADAM8 was markedly higher in HCC tissues than that in the
      normal liver tissues (P = 0.0058).In addition,high expression of ADAM8 protein
      was positively correlated with serum AFP elevation,tumor size,histological
      differentiation,tumor recurrence,tumor metastasis,and tumor stage. Patients with
      higher ADAM8 expression showed a significantly shorter overall survival time than
      patients with low ADAM8 expression. Multivariate analysis suggested that ADAM8
      expression might be an independent prognostic indicator (p = 0.016) for the
      survival of patients with HCC. ADAM8-specific shRNA (shADAM8) successfully
      knocked down its endogenous expression in HepG2 cells. Compared to the parental
      and control shRNA-transfected (shCtrl) HepG2 cells,the shADAM8 cells exhibited
      significantly reduced in vitro cell growth,anchorage-independent growth,cell
      migration and invasion (p < 0.05).In vivo,the xenograft transplants from shADAM8
      cells gave rise to much smaller tumors as compared to those from shCtrl cells.
      High ADAM8 expression is associated with poor overall survival in patients with
      HCC. Down-regulation of ADAM8 inhibits the growth,anchorage-independent
      growth,migration and invasion of HepG2 cells. ADAM8 may be a potential target of
      antiangiogenic therapy for HCC.

PMID- 22965690
TI  - Hyponatraemia: Lixivaptan for euvolaemic hyponatraemia.

PMID- 22965689
TI  - The effects of different UV-B radiation intensities on morphological and
      biochemical characteristics in Ocimum basilicum L.
AB  - BACKGROUND: The effects of short-term ultraviolet B (UV-B) irradiation on sweet
      basil (Ocimum basilicum L. cv. Cinnamon) plants at the 3-4 leaf pair and
      flowering stages were examined in controlled environment growth chambers. Plants
      were exposed to 0 (reference), 2 and 4 kJ UV-B m(-2) day(-1) over 7 days.
      RESULTS: Exposure of basil plants to supplementary UV-B light resulted in
      increased assimilating leaf area, fresh biomass and dry biomass. Stimulation of
      physiological functions in young basil plants under either applied UV-B dose
      resulted in increased total chlorophyll content but no marked variation in
      carotenoid content. At the flowering stage the chlorophyll and carotenoid
      contents of basil were affected by supplementary UV-B radiation, decreasing with
      enhanced UV-B exposure. Both total antioxidant activity (2,2-diphenyl-1
      picrylhydrazyl free radical assay) and total phenolic compound content were
      increased by UV-B light supplementation. Young and mature basil plants differed
      in their ascorbic acid content, which was dependent on UV-B dose and plant age.
      UV-B radiation resulted in decreased nitrate content in young basil plants (3-4
      leaf pair stage). CONCLUSION: These results indicate that the application of
      short-exposure UV-B radiation beneficially influenced both growth parameters and
      biochemical constituents in young and mature basil plants.

PMID- 22965691
TI  - Reduced expression of ELAVL4 in male meningioma patients.
AB  - Meningioma is a frequently occurring tumor of the central nervous system. Among
      many genetic alternations, the loss of the short arm of chromosome 1 is the
      second most frequent chromosomal abnormality observed in these tumors. Here, we
      focused on the previously described and well-established minimal deletion regions
      of chromosome 1. In accordance with the Knudson suppressor theory, we designed an
      analysis of putative suppressor genes localized in the described minimal deletion
      regions. The purpose was to determine the molecular background of the gender
      specific occurrence of meningiomas. A total of 149 samples were examined for loss
      of heterozygosity (LOH). In addition, 57 tumor samples were analyzed using real
      time polymerase chain reaction. We examined the association between the
      expression of selected genes and patient age, gender, tumor grade and presence of
      1p loss. Furthermore, we performed an analysis of the most stable internal
      control for real-time analysis in meningiomas. LOH analysis revealed gender
      specific discrepancies in the frequency of 1p aberrations. Moreover, statistical
      correlation between the gene expression level and gender was significant for the
      ELAVL4 gene as we found it to be lower in males than in females. We conclude that
      meningiomas present different features depending on patient gender. We suggest
      that ELAVL4 can be involved in the pathogenesis of meningiomas in male patients. 

PMID- 22965692
TI  - Greater acceptance of routine HIV testing (opt-out) by patients attending an
      infectious disease unit in Spain.
AB  - OBJECTIVE: Our objective was to determine attitudes and opinions of patients seen
      in our ID Unit on conducting HIV testing universally. METHODS: The survey was
      conducted in patients between 18 and 65 years without known HIV infection.
      Requested information about the test was previous embodiment, reasons for
      rejection, opinion on the universal realization, benefits and/or drawbacks,
      possible test performance, and availability of results "test negative stigma."
      RESULTS: We surveyed 91 patients (54.9% males). Surprisingly, up to 18.7% of
      patients mistakenly believed that HIV testing is routinely performed without
      consent. A great majority (98.9%) felt that universal performance on the test
      would benefit mainly in early diagnosing and/or preventing transmission. Patients
      younger than 42 years were significantly more prone to doing the test as a
      routine procedure. Only 4 (4.4%) patients did not participate because they
      believed they were "not infected." A vast majority (80.5%) of respondents would
      prefer to have results within the first 24 hours. In addition, 20.7% would have a
      problem with confidentiality if HIV serology testing was done. CONCLUSIONS: In
      summary, the vast majority (95.6%) of the surveyed patients had a fair opinion
      about universal HIV testing. Only 4 patients (4.4%) would not consent to HIV
      testing (because of low-risk perception). Availability of rapid HIV tests can
      facilitate fast result delivery, facilitating linkage to care. Considering
      favorable patients' opinion, recent opt-out screening recommendations, highest
      HIV prevalence in admitted patients, and cost-effectiveness, studies favor
      universal HIV testing.

PMID- 22965693
TI  - Bridging the digital divide in HIV care: a pilot study of an iPod personal health
      record.
AB  - BACKGROUND: Persons living with HIV (PLWH) need practical tools to self-manage
      their condition. METHODS: We conducted a proof-of-concept study among PLWH to
      assess whether patients could learn to use a personal health record (PHR) on a
      hand-held device (iPod Touch) to manage their condition. We began individual
      trainings and later adapted this to group training. We assessed usability,
      acceptability and also effects on self-efficacy for treatment adherence using the
      HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES). RESULTS: Nine PLWH
      participated in the individual training and 29 participated in the group
      sessions. The participants were largely middle aged, low-income and of
      racial/ethnic minorities. The sessions were well attended and participants fully
      engaged in tasks and shared learning. Most participants stated they intended to
      use the PHR and reported improved self-efficacy in treatment adherence (P = .05)
      particularly on the integration of treatment adherence into one's routine (P <
      .02). CONCLUSIONS: Training PLWH in use of a handheld PHR shows promise.

PMID- 22965694
TI  - A novel method for the labelling of peptides and proteins through a bioorthogonal
      Staudinger reaction by using 2-cyanoethyl phosphoramidites.
AB  - Chemoselective modification of biomolecules: The reaction between 2-cyanoethyl
      phosphoramidites and azides is economical and can be performed in different
      solvents, including aqueous buffers. The course of the reaction with azido
      modified amino acids, peptides or proteins and different label molecules was
      followed by (31)P NMR spectroscopy.

PMID- 22965695
TI  - Planning a multi-site, complex intervention for homeless people with mental
      illness: the relationships between the national team and local sites in Canada's
      At Home/Chez Soi project.
AB  - This research focused on the relationships between a national team and five
      project sites across Canada in planning a complex, community intervention for
      homeless people with mental illness called At Home/Chez Soi, which is based on
      the Housing First model. The research addressed two questions: (a) what are the
      challenges in planning? and (b) what factors that helped or hindered moving
      project planning forward? Using qualitative methods, 149 national, provincial,
      and local stakeholders participated in key informant or focus group interviews.
      We found that planning entails not only intervention and research tasks, but also
      relational processes that occur within an ecology of time, local context, and
      values. More specifically, the relationships between the national team and the
      project sites can be conceptualized as a collaborative process in which national
      and local partners bring different agendas to the planning process and must
      therefore listen to, negotiate, discuss, and compromise with one another. A
      collaborative process that involves power-sharing and having project coordinators
      at each site helped to bridge the differences between these two stakeholder
      groups, to find common ground, and to accomplish planning tasks within a
      compressed time frame. While local context and culture pushed towards unique
      adaptations of Housing First, the principles of the Housing First model provided
      a foundation for a common approach across sites and interventions. The
      implications of the findings for future planning and research of multi-site,
      complex, community interventions are noted.

PMID- 22965696
TI  - Induction and quantification of prefrontal cortical network plasticity using 5 Hz
      rTMS and fMRI.
AB  - Neuronal plasticity is crucial for flexible interaction with a changing
      environment and its disruption is thought to contribute to psychiatric diseases
      like schizophrenia. High-frequency repetitive transcranial magnetic stimulation
      (rTMS) is a noninvasive tool to increase local excitability of neurons and induce
      short-time functional reorganization of cortical networks. While this has been
      shown for the motor system, little is known about the short-term plasticity of
      networks for executive cognition in humans. We examined 12 healthy control
      subjects in a crossover study with fMRI after real and sham 5 Hz rTMS to the
      right dorsolateral prefrontal cortex (DLPFC). During scanning, subjects performed
      an n-back working memory (WM) task and a flanker task engaging cognitive control.
      Reaction times during the n-back task were significantly shorter after rTMS than
      after sham stimulation. RTMS compared with sham stimulation caused no activation
      changes at the stimulation site (right DLPFC) itself, but significantly increased
      connectivity within the WM network during n-back and reduced activation in the
      anterior cingulate cortex during the flanker task. Reduced reaction times after
      real stimulation support an excitatory effect of high-frequency rTMS. Our
      findings identified plastic changes in prefrontally connected networks downstream
      of the stimulation site as the substrate of this behavioral effect. Using a
      multimodal fMRI-rTMS approach, we could demonstrate changes in cortical
      plasticity in humans during executive cognition. In further studies this approach
      could be used to study pharmacological, genetic and disease-related alterations.

PMID- 22965697
TI  - Which research is needed to support clinical decision-making on integrative
      medicine?- Can comparative effectiveness research close the gap?
AB  - In clinical research on complementary and integrative medicine, experts and
      scientists have often pursued a research agenda in spite of an incomplete
      understanding of the needs of end users. Consequently, the majority of previous
      clinical trials have mainly assessed the efficacy of interventions. Scant data is
      available on their effectiveness. Comparative effectiveness research (CER)
      promises to support decision makers by generating evidence that compares the
      benefits and harms of the best care options. This evidence, more generalizable
      than the evidence generated by traditional randomized controlled trials (RCTs),
      is better suited to inform real-world care decisions. An emphasis on CER supports
      the development of the evidence base for clinical and policy decision-making.
      Whereas in most areas of complementary and integrative medicine data on
      comparative effectiveness is scarce, available acupuncture research already
      contributes to CER evidence. This paper will introduce CER and make suggestions
      for future research.

PMID- 22965698
TI  - Establishing Chinese medicine characteristic tumor response evaluation system is
      the key to promote internationalization of Chinese medicine oncology.
AB  - The features and advantages of Chinese medicine (CM) in cancer comprehensive
      treatment have been in the spotlight of experts both at home and abroad. However,
      how to evaluate the effect of CM more objectively, scientifically and
      systematically is still the key problem of clinical trial, and also a limitation
      to the development and internationalization of CM oncology. The change of tumor
      response evaluation system in conventional medicine is gradually consistent with
      the features of CM clinical effect, such as they both focus on a combination of
      soft endpoints (i.e. quality of life, clinical benefit, etc.) and hard endpoints
      (i.e. tumor remission rate, time to progress, etc.). Although experts have
      proposed protocols of CM tumor response evaluation criteria and come to an
      agreement in general, divergences still exist in the importance, quantification
      and CM feature of the potential endpoints. Thus, establishing a CM characteristic
      and wildly accepted tumor response evaluation system is the key to promote
      internationalization of CM oncology, and also provides a more convenient and
      scientific platform for CM international cooperation and communication.

PMID- 22965699
TI  - Clinical study of western medicine combined with Chinese medicine based on
      syndrome differentiation in the patients with polarized hypertension.
AB  - OBJECTIVE: To investigate the effects and safety of Western medicine combined
      with Chinese medicine (CM) based on syndrome differentiation in the treatment of
      elderly polarized hypertension (PHPT), or isolated systolic hypertension with low
      diastolic blood pressure (DBP). METHODS: A total of 125 elderly patients with
      PHPT were randomly assigned to two groups: 59 in the control group treated by
      Western medicine and 66 in the intervention group treated by Western medicine
      combined with CM treatment. Based on syndrome differentiation, the patients in
      the intervention group were further divided into subgroups of yang-qi deficiency
      and yin-qi deficiency. All subjects were treated with Western medicine of
      Amlodipine Besylate Tablets and Irbesartan Tablets (or Irbesartan and
      Hydrochlorothiazide Tablets), to decrease their systolic blood pressure (SBP)
      slowly to 125-135 mm Hg in 2-6 weeks. In the intervention group, Shiyiwei Shenqi
      Capsule was given additionally to the subgroup of yang-qi deficiency at the
      dosage of 3-5 capsules, thrice a day, while Dengzhan Shengmai Capsule was given
      additionally to the subgroup of yin-qi deficiency at the dosage of 2 capsules, 2
      3 times per day. For all subjects, SBP, pulse pressure (PP), and DBP were
      measured before treatment and at the terminal of a 6-week treatment. For subjects
      in the intervention group, left ventricular ejection fraction (LVEF) was also
      recorded. RESULTS: After a 6-week treatment, the SBP in the two groups and the PP
      in the intervention group decreased significantly compared to those before
      treatment (P<0.05), while the PP in the control group showed no significant
      difference between prior and post-treatment (P>0.05). After treatment, the DBP in
      the control group decreased (P>0.05), while the DBP and LVEF in the intervention
      group showed an increase tendency although it had no statistical significance
      (P>0.05). When subjects in the intervention group were classified further by the
      course of disease, the DBP and LVEF of subjects whose course of disease were less
      than 2 years, increased significantly after treatment (P<0.05). CONCLUSION:
      Western medicine combined with CM treatment based on syndrome differentiation was
      safer and more effective than Western medicine alone in the treatment of elderly
      PHPT, because it not only reduced SBP but also improved DBP, which might lower
      the incidence of the cardiovascular and cerebrovascular events.

PMID- 22965700
TI  - Effects of different therapeutic methods and typical recipes of Chinese medicine
      on activation of c-Jun N-terminal kinase in kupffer cells of rats with fatty
      liver disease.
AB  - OBJECTIVE: To observe the effects of different therapeutic methods and the
      recipes of Chinese medicine (CM) on the activation of c-Jun N-terminal kinase
      (JNK) in Kupffer cells of rats with fatty liver disease and to explore the
      mechanisms of these therapeutic methods. METHODS: By using a random number table,
      98 rats were randomly divided into 7 groups: control group, model group, and 5
      treatment groups, including soothing Liver (Gan) recipe group, invigorating
      Spleen (Pi) recipe group, dispelling dampness recipe group, promoting blood
      recipe group, and complex recipe group. Rats in the control group were fed with
      normal food and distilled water by gastric perfusion, while rats in the model
      group were fed with high-fat food and distilled spirits by gastric perfusion.
      Rats in the 5 treatment groups were fed with high-fat food and corresponding
      recipes by gastric perfusion. Twelve weeks later, all rats were sacrificed and
      liver tissues were stained for pathohistological observation. Kupffer cells were
      isolated from livers of rats to evaluate JNK and phospho-JNK expressions by
      Western blotting. RESULTS: The grade of hepatic steatosis was higher in the model
      group than the control group (P<0.05). Compared with the model group, the grade
      of fatty degeneration in soothing Liver recipe group and invigorating Spleen
      recipe group were significantly ameliorated (P<0.05). Expressions of JNK and
      phospho-JNK in Kupffer cells were significantly higher in the model group than
      those in the control group (P<0.05, P<0.01). Compared with the model group,
      expressions of JNK in all treatment groups decreased, especially in invigorating
      Spleen recipe group and promoting blood recipe group (P<0.05). Compared with the
      model group, expressions of phospho-JNK in all treatment groups declined
      significantly (P<0.01), especially in soothing Live recipe group and invigorating
      Spleen recipe group. CONCLUSIONS: The high expressions of JNK and phospho-JNK in
      Kupffer cells might play an important role in the pathogenesis of fatty liver
      disease in rats. The recipes of CM, especially invigorating Spleen recipe and
      soothing Liver recipe, might protect liver against injury by reducing the total
      JNK protein content and inhibiting the activation of JNK protein in Kupffer cells
      of fatty liver model rats, which showed beneficial effects on fatty liver
      disease.

PMID- 22965701
TI  - Variations in the composition of Fructus Evodiae after processing with Radix
      Glycyrrhizae extract.
AB  - OBJECTIVE: To evaluate the changes in the concentrations of five components in
      Fructus Evodiae used in Chinese medicine, including evodiamine and glycyrrhizic
      acid, during processing of Fructus Evodiae with Radix Glycyrrhizae extract by
      using high performance liquid chromatography (HPLC) and to provide a scientific
      basis for different clinical uses of processed and unprocessed Fructus Evodiae.
      METHODS: The concentrations of the Fructus Evodiae components in processed or
      unprocessed Fructus Evodiae were evaluated by HPLC using a YMC J'sphere ODS-H80
      column (4.6 mm*250 mm, 5 MUm) with acetonitrile-water-tetrahydrofuran-acetic acid
      (41:59:1:0.2, v/v/v/v) as the mobile phase. The detection wavelength was 225 nm,
      the column temperature was 35 degrees C, the flow rate was 1.0 mL/min, and the
      injection volume was 10 MUL. The concentrations of the Radix Glycyrrhizae
      components were determined by HPLC with a Kromasil-C18 column (4.6 mm*250 mm, 4
      MUm) and a gradient elution of acetonitrile (A) and 0.05% aqueous phosphoric acid
      (B) as the mobile phase. The detection wavelength was 237 nm, the column
      temperature was 35  degrees C, the flow rate was 1.0 mL/min, and the injection
      volume was 10 MUL. RESULTS: The calibration curves of evodia lactone, evodiamine,
      rutaecarpine, liquiritin, and glycyrrhizin showed good linear relationships
      (r>0.99). The recoveries of evodia lactone, evodiamine, rutaecarpine, liquiritin,
      and glycyrrhizin were 96.59%, 104.18%, 101.91%, 97.75%, and 97.95%, respectively.
      The concentrations of the components in processed Fructus Evodiae were obviously
      different to those in unprocessed Fructus Evodiae. CONCLUSIONS: The developed
      method is rapid and accurate. The results provide a reference for processed
      Fructus Evodiae and the changes that could be expected in its effects compared to
      unprocessed Fructus Evodiae.

PMID- 22965702
TI  - Malignant gastric cancer cured by short-term chemotherapy and long-term use of
      combined chinese medicine: a case report.

PMID- 22965703
TI  - Hematopoietic stem cell transplantation and rhinosinusitis: the utility of
      screening sinus computed tomography.
AB  - OBJECTIVES/HYPOTHESIS: To compare prehematopoietic stem cell transplantation
      (SCT) sinus computed tomography (CT) scans to post-SCT sinus CT scans and to
      evaluate the relationship between pre-SCT sinus CT scans and the incidence of
      otolaryngology consultation after SCT. STUDY DESIGN: Retrospective chart review.
      METHODS: Charts of 228 adult SCT patients from January 2003 to June 2009 with pre
      SCT sinus CT scans were reviewed. Data gathered included diagnosis, type of SCT,
      otolaryngology referral requests, and rhinosinusitis management. Pre- and post
      SCT sinus CT scans were scored using the staging system introduced by Lund and
      Mackay. RESULTS: Two hundred thirty-nine SCTs were performed on the 228 patients
      included in this study. No disease was identified on 25.1% of pre-SCT CT scans,
      mild sinus inflammation was identified on 60.7% of scans, 11.3% had moderate
      inflammation, and 2.9% had severe inflammation. Pre-SCT scans were found to be
      predictive of post-SCT CT scans. A significant proportion of patients
      demonstrated worsening of their Lund-Mackay score post-SCT. Pre-SCT CT scores had
      no predictive ability for otolaryngology consultations. CONCLUSIONS: Pre-SCT CT
      scan scores are associated with post-SCT scan scores; disease severity on CT may
      worsen following SCT and may be useful for stratifying patients into surgical
      versus non-surgical candidates. Further study is needed to outline the benefit of
      sinus surgery in these patients.

PMID- 22965705
TI  - Instrumentation design for hydrodynamic sample injection in microchip
      electrophoresis: a review.
AB  - Reproducible and representative sample injection in microchip electrophoresis has
      been a bottleneck for quantitative analytical applications. Electrokinetic sample
      injection is the most used because it is easy to perform. However, this injection
      method is usually affected by sample composition and the bias effect. On the
      other hand, these drawbacks are overcome by the hydrodynamic (HD) sample
      injection, although this injection mode requires HD flow control. This review
      gives an overview of the basic principles, the instrumentation designs, and the
      performance of HD sample injection systems for microchip electrophoresis.

PMID- 22965706
TI  - Microchip capillary electrophoresis instrumentation for in situ analysis in the
      search for extraterrestrial life.
AB  - The search for signs of life on extraterrestrial planetary bodies is among NASA's
      top priorities in Solar System exploration. The associated pursuit of organics
      and biomolecules as evidence of past or present life demands in situ
      investigations of planetary bodies for which sample return missions are neither
      practical nor affordable. These in situ studies require instrumentation capable
      of sensitive chemical analyses of complex mixtures including a broad range of
      organic molecules. Instrumentation must also be capable of autonomous operation
      aboard a robotically controlled vehicle that collects data and transmits it back
      to Earth. Microchip capillary electrophoresis (MUCE) coupled to laser-induced
      fluorescence (LIF) detection provides this required sensitivity and targets a
      wide range of relevant organics while offering low mass, volume, and power
      requirements. Thus, this technology would be ideally suited for in situ studies
      of astrobiology targets, such as Mars, Europa, Enceladus, and Titan. In this
      review, we introduce the characteristics of these planetary bodies that make them
      compelling destinations for extraterrestrial astrobiological studies, and the
      principal groups of organics of interest associated with each. And although the
      technology we describe here was first developed specifically for proposed studies
      of Mars, by summarizing its evolution over the past decade, we demonstrate how
      MUCE-LIF instrumentation has become an ideal candidate for missions of
      exploration to all of these nearby worlds in our Solar System.

PMID- 22965707
TI  - Microfabricated devices for biomolecule encapsulation.
AB  - Biomolecule encapsulation in droplets is important for miniaturizing biological
      assays to reduce reagent consumption, cost and time of analysis, and can be most
      effectively achieved by using microfabricated devices. Microfabricated fluidic
      devices can generate emulsified drops of uniform size with controlled dimensions
      and contents. Biological and chemical components such as cells, microgels, beads,
      hydrogel precursors, polymer initiators, and other droplets can be encapsulated
      within these drops. Encapsulated emulsions are appealing for a variety of
      applications since drops can be used as tiny reaction vessels to perform high
      throughput reactions at fast rates, consuming minimal sample and solvent amounts
      due to the small size (micron diameters) of the emulsion drops. Facile mixing and
      droplet coalescence allow for a diversity of assays to be performed on-chip with
      tunable parameters. The simplicity of operation and speed of analysis with
      microencapsulated drops lends itself well to an array of quantitative
      biomolecular studies such as directed evolution, single-molecule DNA
      amplification, single-cell encapsulation, high-throughput sequencing, enzyme
      kinetics, and microfluidic cell culture. This review highlights recent advances
      in the field of microfabricated encapsulating devices, emphasizing the
      development of emulsifying encapsulations, device design, and current assays that
      are performed using encapsulating droplets.

PMID- 22965708
TI  - Unmanned platform for long-range remote analysis of volatile compounds in air
      samples.
AB  - This paper describes a long-range remotely controlled CE system built on an all
      terrain vehicle. A four-stroke engine and a set of 12-V batteries were used to
      provide power to a series of subsystems that include drivers, communication,
      computers, and a capillary electrophoresis module. This dedicated instrument
      allows air sampling using a polypropylene porous tube, coupled to a flow system
      that transports the sample to the inlet of a fused-silica capillary. A hybrid
      approach was used for the construction of the analytical subsystem combining a
      conventional fused-silica capillary (used for separation) and a laser machined
      microfluidic block, made of PMMA. A solid-state cooling approach was also
      integrated in the CE module to enable controlling the temperature and therefore
      increasing the useful range of the robot. Although ultimately intended for
      detection of chemical warfare agents, the proposed system was used to analyze a
      series of volatile organic acids. As such, the system allowed the separation and
      detection of formic, acetic, and propionic acids with signal-to-noise ratios of
      414, 150, and 115, respectively, after sampling by only 30 s and performing an
      electrokinetic injection during 2.0 s at 1.0 kV.

PMID- 22965709
TI  - Polyester-toner electrophoresis microchips with improved analytical performance
      and extended lifetime.
AB  - This paper reports the fabrication of polyester-toner (PT) electrophoresis
      microchips with improved analytical performance and extended lifetime. This has
      been achieved with a better understanding about the EOF generation and the
      influence of some parameters including the channel dimensions (width and depth),
      the injection mode, and the addition of organic solvent to the running buffer.
      The analytical performance of the PT devices was investigated using a
      capacitively coupled contactless conductivity detector and inorganic cations as
      model analytes. The proposed devices have exhibited EOF values of (3.4 +/- 0.2) *
      10(-4) cm(2) V(-1) s(-1) with good stability over 25 consecutive runs. It has
      been found that the EOF magnitude depends on the channel dimension, i.e. the
      wider the channel, the higher the EOF value. The separation efficiency for
      inorganic cations ranged from 13 000 to 50 000 plates/m. The LOD found for K(+) ,
      Na(+) , and Li(+) were 4.2, 7.3, and 23 MUM, respectively. In addition, the same
      PT device has been used by three consecutive days. Lately, due to improved
      analytical performance, it was carried out by the first time the detection of
      inorganic cations in real samples such as energetic drinks and pharmaceutical
      formulations.

PMID- 22965710
TI  - Fluid mixing using AC electrothermal flow on meandering electrodes in a
      microchannel.
AB  - The mixing of fluids using AC electrothermal flow (AC-ETF) is presented. A pair
      of coplanar electrodes with a sinusoidal interelectrode gap was used to enhance
      the mixing in a microchannel. To demonstrate the performance of the mixer,
      conventional dilution experiments were conducted using Texas Red-labeled dextran.
      The dependence of mixing on the salt concentration (10(-3) ~ 10(-1) mol dm(-3) )
      of the solutions and frequency (100 kHz ~ 5 MHz) of the applied voltage were
      investigated. AC-ETF was responsible for the mixing at salt concentrations >10(
      2) mol dm(-3) , whereas the effect of AC-EOF was suggested to play a role at
      concentrations <10(-2) mol dm(-3) in the low-frequency region. The fluorogenic
      reaction of human serum albumin (HSA) with SYPRO Red in the mixer was also
      examined, and results showed that enrichment of fluorescence intensity and an
      almost uniform distribution of stained HSA were achieved. The present mixer can
      be employed as a powerful tool to facilitate efficient chemical and biomedical
      analysis on microfluidic devices.

PMID- 22965711
TI  - Thermally responsive phospholipid preparations for fluid steering and separation
      in microfluidics.
AB  - Aqueous phospholipid preparations comprised of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) are
      prevalent materials for biological characterization and become gel-like near
      physiological temperature, but have a low viscosity below 24 degrees C. The
      rheology of 20% phospholipid preparations of [DMPC]/[DHPC] = 2.5 reveals that,
      under conditions utilized for fluid steering, the materials are shear-thinning
      power-law fluids with a power-law index ranging from 0.30 through 0.90.
      Phospholipid preparations are utilized to steer fluids in microfluidic chips and
      support hydrodynamic delivery of sample across a double T injection region in a
      chip. The fact that the phospholipids are fully integrated as a valving material
      as well as a separation medium is demonstrated through the separation of linear
      oligosaccharides labeled with 1-aminopyrene-3,6,8-trisulfonic acid.

PMID- 22965712
TI  - Electrowetting on dielectric actuation of droplets with capillary electrophoretic
      zones for MALDI mass spectrometric analysis.
AB  - An automated fraction collection interface was developed for coupling CE with
      MALDI-MS. This fraction collection approach is based on the electrowetting on
      dielectric (EWOD) phenomenon performed on a digital microfluidic (DMF) board; it
      does not rely on a MALDI spotter. In this study, a four-peptide mixture was used
      as a sample test, and the separations were conducted in a portable CE instrument
      with a 150 MUm o.d. * 50 MUm i.d. capillary and a contactless conductivity
      detector. The CE instrument was interfaced with a robust DMF board. The CE
      fractions were directly deposited onto the DMF board at predetermined locations
      prior to MALDI analysis. The series of experiments determined the lowest
      concentration that produces a measurable MALDI signal. The concentrations were
      0.25, 0.5, 0.05, and 0.05 nmol for bradykinin, angiotensin, ACTH (18-39), and
      insulin, respectively. The contactless conductivity detector limit of detection
      for the same analytes was 2.5 MUmol.

PMID- 22965713
TI  - Development and characterization of a novel semiautomated arrangement for
      electrochemically assisted injection in combination with capillary
      electrophoresis time-of-flight mass spectrometry.
AB  - Electrochemically assisted injection (EAI) is an attractive injection concept for
      CE that enables the separation of neutral analytes via electrochemical generation
      of charged species during the injection process. A new semiautomated EAI
      configuration was developed and applied in conjunction with CE-MS (EAI-CE-MS).
      The EAI cell arrangement consists of an integrated buffer reservoir for CE
      separations and a compartment holding screen-printed electrodes. A drop of sample
      solution (50 MUL) was sufficient to cover the three-electrode structures. A piezo
      motor provided a fast and precise capillary positioning over the screen-printed
      electrode assembly. Using ferrocene methanol as a model system, the EAI
      arrangement was characterized regarding coulometric efficiency, precision, and
      sensitivity of electrospray ionization-time-of-flight-MS. The formation of the
      cationic oxidation product of ferrocene methanol enhanced the sensitivity of CE
      MS determination by two orders of magnitude and the electrochemically formed
      product showed a migration time corresponding to its individual electrophoretic
      mobility. Preliminary studies of EAI-CE-MS in the field of the analysis of
      nitroaromatic compounds were carried out. The formation of corresponding
      hydroxylamines and amines paved the way for selective and sensitive CE-MS
      determinations without the need of adding surfactants to the electrophoresis
      buffer.

PMID- 22965714
TI  - Electrokinetic injection across supported liquid membranes: new sample
      pretreatment technique for online coupling to capillary electrophoresis. Direct
      analysis of perchlorate in biological samples.
AB  - A simple and sensitive method for quantifying perchlorate in biological samples
      using CE and capacitively coupled contactless conductivity detection was
      developed. An online combination of a supported liquid membrane, an inert
      polypropylene membrane impregnated with 1-hexanol, and electrokinetic injection
      of perchlorate across the supported liquid membrane directly into the separation
      capillary reduced the need for laborious sample pretreatment procedures,
      resulting in a cheap and rapid method with low LODs capability. Baseline
      separation of perchlorate and other anions in biological samples was achieved in
      background electrolyte solution consisting of 15 mM nicotinic acid and 1 mM 3
      (N,N-dimethylmyristylammonio)propanesulfonate at pH 3.3. The analytical method
      showed excellent parameters in terms of reproducibility; RSD values for peak
      areas and corrected migration times at a spiked concentration of 100 MUg/L of
      perchlorate were below 10 and 0.4%, respectively. Linear calibration curves were
      obtained for perchlorate in the concentration range 10-1000 MUg/L (r(2) >0.999)
      with LODs between 2 and 5 MUg/L for human urine, breast milk, serum, cow's milk,
      and red wine. Recoveries at 25 MUg/L of perchlorate were between 97 and 106% for
      all biological samples. The low LODs rivaling those of presently used analytical
      methods support the use of this method for quantification of perchlorate in
      biological samples in the future.

PMID- 22965715
TI  - Micellar affinity gradient focusing in a microfluidic chip with integrated
      bilinear temperature gradients.
AB  - Micellar affinity gradient focusing (MAGF) is a microfluidic counterflow gradient
      focusing technique that combines the favorable features of MEKC and temperature
      gradient focusing. MAGF separates analytes on the basis of a combination of
      electrophoretic mobility and partitioning with the micellar phase. A temperature
      gradient is produced along the separation channel containing an analyte/micellar
      system to create a gradient in interaction strength (retention factor) between
      the analytes and micelles. Combined with a bulk counterflow, species concentrate
      at a unique point where their total velocity sums to zero. MAGF can be used in
      scanning mode by varying the bulk flow so that a large number of analytes can be
      sequentially focused and passed by a single detection point. In this work, we
      develop a bilinear temperature gradient along the separation channel that
      improves separation performance over the conventional linear designs. The
      temperature profile along the channel consists of a very sharp gradient used to
      preconcentrate the sample followed by a shallow gradient that increases
      resolution. We fabricated a hybrid PDMS/glass microfluidic chip with integrated
      micro heaters that generate the bilinear profile. Performance is characterized by
      separating several different samples including fluorescent dyes using SDS
      surfactant and pI markers using both SDS and poly-SUS surfactants as the micellar
      phase. The new design shows a nearly two times improvement in peak capacity and
      resolution in comparison to the standard linear temperature gradient.

PMID- 22965716
TI  - Implementation of a genetically tuned neural platform in optimizing fluorescence
      from receptor-ligand binding interactions on microchips.
AB  - This paper describes the use of a genetically tuned neural network platform to
      optimize the fluorescence realized upon binding 5-carboxyfluorescein-D-Ala-D-Ala
      D-Ala (5-FAM-(D-Ala)(3) ) (1) to the antibiotic teicoplanin from Actinoplanes
      teichomyceticus electrostatically attached to a microfluidic channel originally
      modified with 3-aminopropyltriethoxysilane. Here, three parameters: (i) the
      length of time teicoplanin was in the microchannel; (ii) the length of time 1 was
      in the microchannel, thereby, in equilibrium with teicoplanin, and; (iii) the
      amount of time buffer was flushed through the microchannel to wash out any
      unbound 1 remaining in the channel, are examined at a constant concentration of
      1, with neural network methodology applied to optimize fluorescence. Optimal
      neural structure provided a best fit model, both for the training set (r(2) =
      0.985) and testing set (r(2) = 0.967) data. Simulated results were experimentally
      validated demonstrating efficiency of the neural network approach and proved
      superior to the use of multiple linear regression and neural networks using
      standard back propagation.

PMID- 22965717
TI  - High electric field strength two-dimensional peptide separations using a
      microfluidic device.
AB  - New instrumentation has been developed to improve the resolution, efficiency, and
      speed of microfluidic 2D separations using MEKC coupled to high field strength
      CE. Previously published 2D separation instrumentation [Ramsey, J. D. et al.,
      Anal. Chem. 2003, 75, 3758-3764] from our group was limited to a maximum
      potential difference of 8.4 kV, resulting in an electric field strength of only
      approximately 200 V/cm in the first dimension. The circuit described in this
      report has been designed to couple a higher voltage supply with a rapidly
      switching, lower voltage supply to utilize the best features of each. Voltages
      applied in excess of 20 kV lead to high electric field strength separations in
      both dimensions, increasing the separation resolution, efficiency, and peak
      capacity while reducing the required analysis time. Detection rates as high as
      six peptides per second (based on total analysis time) were observed for a model
      protein tryptic digest separation. Additionally, higher applied voltages used in
      conjunction with microfluidic chips with longer length channels maintained higher
      electric field strengths and produced peak capacities of over 4000 for some
      separations. Total separation time in these longer channel devices was comparable
      to that obtained in short channels at low field strength; however, resolving
      power improved approximately threefold.

PMID- 22965718
TI  - A parallel dual-electrode detector for capillary electrophoresis.
AB  - An approach to on-capillary dual-electrode detection for CE using a parallel
      electrode configuration has been developed. The parallel configuration provides
      two operating modes. In the first mode, one working electrode is held at an
      oxidizing potential and the second working electrode is held at a reducing
      potential. This results in redox cycling of analytes between the oxidized and
      reduced forms, enhancing sensitivity compared to single-electrode detection. In
      the second mode, both working electrodes are held at different oxidizing
      potentials. This mode provides electrochemical characterization of
      electrophoretic peaks. In the redox cyclying mode, signal enhancement of up to
      twofold was observed for the dual-electrode detection of phenolic acid standards
      compared to single-electrode detection. Variation in response of less than 10%
      from electrode to electrode was determined (at a concentration of 60 nM)
      indicating reproducible fabrication. LODs were determined to be as low as 5.0 nM
      for dual-electrode configuration. Using the dual-potential mode peak
      identification of targeted phenolic acids in whiskey samples were confirmed based
      on both migration time and current ratios.

PMID- 22965719
TI  - Smart portable electrophoresis instrument based on multipurpose microfluidic
      chips with electrochemical detection.
AB  - A second generation of a battery-powered portable electrophoresis instrument for
      the use of ME with electrochemical detection was developed. As the first
      generation, the main unit of the instrument (150 mm * 165 mm * 95 mm) consists of
      four-outputs high-voltage power supply (HVPS) with maximum voltage of 3 KV and
      acquisition system (bipotentiostat) containing 2-channels for dual
      electrochemical detection. A new reusable microfluidic platform was designed in
      order to incorporate the microchips with the portable instrument. In this case,
      the platform is integrated to the main unit of the instrument so that it is not
      necessary to have any external cable for the interconnection of both parts,
      making the use of the complete system easier. The new platform contains all the
      electrical connections for the HVPS and bipotentiostat, as well as fluidic ports
      for driving the solutions. The microfluidic electrophoresis instrument is
      controlled by means of a user-friendly interface from a computer. The possibility
      of wireless connection (Bluetooth(r)) allows the use of the instrument without
      any external cable improving the portability. Therefore, the second generation
      brings a more compact and integrated electrophoresis instrument for "in situ"
      applications using microfluidic chips in an easy way. The performance of the
      electrophoresis system was initially evaluated using single- and dual-channel SU
      8/Pyrex microchips with different models of integrated electrodes including
      microelectrodes and interdigitated arrays. The method was tested in different
      analytical applications such as separation of neurotransmitters, chlorophenols,
      purine derivatives, vitamins, polyphenolic acids, and flavones.

PMID- 22965720
TI  - Sheath-flow electrochemical detection of amino acids with a copper wire electrode
      in capillary electrophoresis.
AB  - Here, we report the detection of native amino acids using a sheath-flow
      electrochemical detector with a working electrode made of copper wire. A
      separation capillary that was inserted into a platinum tube in the detector acted
      as a grounded electrode for electrophoresis and as a flow channel for sheath
      liquid. Sheath liquid flowed outside the capillary to support the transport of
      the separated analytes to the working electrode for electrochemical detection.
      The copper wire electrode was aligned at the outlet of the capillary in a wall
      jet configuration. Amino acids injected into the capillary were separated
      following elution from the end of the capillary and detection by the copper
      electrode. Three kinds of copper electrodes with different diameters-50, 125, and
      300 MUm-were examined to investigate the effect of the electrode diameter on
      sensitivity. The peak widths of the analytes were independent of the diameter of
      the working electrode, while the 300-MUm electrode led to a decrease in the
      signal-to-noise ratio compared with the 50- and 125-MUm electrodes, which showed
      no significant difference. The flow rate of the sheath liquid was also varied to
      optimize the detection conditions. The limits of detection for amino acids ranged
      from 4.4 to 27 MUM under optimal conditions.

PMID- 22965721
TI  - Desktop near-field thermal-lens microscope for thermo-optical detection in
      microfluidics.
AB  - A new compact near-field desktop-sized diode laser thermal-lens microscope for
      analysis in microfluidics was proposed. A novel beam-alignment and detection
      systems provided high signal stability and, along with reduced number of optical
      elements rendered the instrument portable. The detection of nonfluorescent model
      species (Fe(II)-bathophenanthroline chelate) in water showed good linearity in
      the range of 5 * 10(-9) to 1 * 10(-4) M, and the limit of detection was 3.5 * 10(
      9) M, which corresponded to 3.5 * 10(-7) absorbance units and provided a 20-fold
      enhancement in sensitivity compared with existing schematic.

PMID- 22965722
TI  - Light-emitting diode induced fluorescence (LED-IF) detection design for a pen
      shaped cartridge based single capillary electrophoresis system.
AB  - CGE is a well-established separation technique for the analysis of biologically
      important molecules such as nucleic acids. The inherent high resolving power,
      rapid analysis times, excellent detection sensitivity, and quantification
      capabilities makes this method favorable compared to conventional manual
      polyacrylamide and agarose slab gel electrophoresis techniques. In this paper we
      introduce a novel single-channel capillary gel electrophoresis system with LED
      induced fluorescence detection also utilizing a compact pen-shaped capillary
      cartridge design for automatic analysis of samples from a 96-well plate. To
      evaluate the suitability of the system, 1000 genomic DNA(gDNA) samples were
      analyzed in gel filled capillaries and detected by the microball ended excitation
      and emission optical fiber based LED-induced fluorescence detection system.
      Excellent migration time reproducibility of RSD <0.75% was obtained over the
      course of 1000 runs. The system rapidly distinguished between intact and degraded
      gDNA samples, therefore provided important information if they could be used for
      downstream quantitative PCR processing where high-quality intact gDNA was key. We
      envision that this novel system design will rapidly find new applications in both
      research and clinical diagnostic laboratories as a highly sensitive and easy to
      use bio-analytical approach.

PMID- 22965723
TI  - In situ particle zeta potential evaluation in electroosmotic flows from time
      resolved microPIV measurements.
AB  - A time-resolved microPIV method is presented to measure in an EOF the particles
      zeta potential in situ during the transient start-up of a microdevice. The method
      resolves the electrophoretic velocity of fluoro-spheres used as tracer particles
      in microPIV. This approach exploits the short transient regime of the EOF
      generated after a potential drop is imposed across a microchannel and before
      reaching quasisteady state. During the starting of the transient regime, the
      electrophoretic effect is dominant in the center of the channel and the EOF is
      negligible. By measuring the velocity of the tracer particles with a microPIV
      system during that starting period, their electrophoretic velocity is obtained.
      The technique also resolves the temporal evolution of the EOF with three regions
      identified. The first region occurs before the electroosmotic effect reaches the
      center of the channel, the second region extends until the EOF reaches steady
      state, and thereafter is the third region. The two time constants separating
      these regions are also obtained and compared to the theory. The zeta potential of
      860 nm diameter polystyrene particles is calculated for different solutions
      including borate buffer, sodium chloride, and deionized water. Results show that
      the magnitudes of the electrophoretic and electroosmotic velocities are in the
      range of |300| to |700| MUm/s for these measurements. The zeta potential values
      are compared to the well-established closed cell technique showing improved
      accuracy. The method also resolves the characteristic response time of the EOF,
      showing small but important deviations from current analytical predictions.
      Additionally, the measurements can be performed in situ in microfluidic devices
      under actual working EOF conditions and without the need for calibrations.

PMID- 22965724
TI  - Comparative microRNA detection from precursor-microRNA-transfected hepatocellular
      carcinoma cells by capillary electrophoresis with dual-color laser-induced
      fluorescence.
AB  - A dual-LIF (dLIF) setup combined with CE for microRNA (miRNA) detection is
      proposed in this study. An argon ion laser (488 nm) and a solid state laser (640
      nm) were chosen to excite the fluorescent dye-labeled DNA probe after splinted
      ligation of miRNA. The crosstalk of emission spectrum of Alex Fluor 488 and Alex
      Fluor 647 is minimized with a zero crosstalk matrix for Alex Fluor 647 to 488
      channels. The linear ranges of the device for the fluorescent dye-labeled DNA
      probe were both from 1.0 nM to 0.1 pM. The limits of detection for Alexa Fluor
      488-labeled DNA and Alex Fluor 647-labeled DNA were 9.3 and 31 fM, respectively.
      The detection of specific miRNA has been accomplished by combining splinted
      ligation with the fluorescent dye-labeled oligonucleotides. The linear range for
      the synthetic miRNA is from 1.0 nM to 1.0 pM. Without PCR amplification, CE-dLIF
      was applied to discriminate a pre-miR-10b*-transfected cells (contains precursor
      miR-10b*) from hepatocellular carcinoma cell (control cells). Therefore, this
      result indicates CE-dLIF has great potential to provide a rapid comparative assay
      for miRNAs detection.

PMID- 22965725
TI  - Development and validation of a capillary electrophoresis method with
      capacitively coupled contactless conductivity detection (CE-C(4) D) for the
      analysis of amikacin and its related substances.
AB  - Amikacin is a semisynthetic aminoglycoside antibiotic derived from kanamycin A
      that lacks a strong UV absorbing chromophore or fluorophore. Due to the
      physicochemical properties of amikacin and its related substances, CE in
      combination with capacitively coupled contactless conductivity detection (CE-C(4)
      D) was chosen. The optimized separation method uses a BGE composed of 20 mM MES
      adjusted to pH 6.6 by l-histidine and 0.3 mM CTAB that was added as flow modifier
      in a concentration below the CMC. Ammonium acetate 20 mg.L(-1) was used as
      internal standard. 30 kV was applied in reverse polarity on a fused silica
      capillary (73/48 cm; 75 MUm id). The optimized separation was obtained in less
      than 6 min with good linearity (R(2) = 0.9996) for amikacin base. It shows a good
      precision expressed as RSD on relative peak areas equal to 0.1 and 0.7% for
      intraday and interday, respectively. The LOD and LOQ are 0.5 mg.L(-1) and 1.7
      mg.L(-1) , respectively.

PMID- 22965726
TI  - Selection of bovine catalase aptamers using non-SELEX.
AB  - In this research, we used the non-SELEX method to successfully select an aptamer
      that binds to the protein target (bovine catalase) with a K(D) value in the low
      micro molar range. The time window was determined for the target and aptamer
      library by optimizing the buffer conditions using 3 * Tris-glycine-potassium
      phosphate (TGK) buffer as the run buffer and 1* TGK as the selection buffer to
      give the biggest complex peak. Fractions were collected by multistep
      nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM)-based
      partitioning for three rounds of selection. The fractions from each round were
      enriched using PCR and the progress of selection was monitored using bulk
      affinity analysis. Fraction 2 was determined to have the optimal bulk affinity
      (0.75 MUM) and this enriched library was cloned and sequenced giving four aptamer
      sequences. These sequences were verified using affinity capillary electrophoresis
      (CAT 1 0.237 MUM) and fluorescence intensity measurements (CAT 1 0.430 MUM). The
      specificity of the aptamer was also determined by fluorescence intensity
      measurements. The results showed that the aptamer with the highest binding
      affinity showed at least a 100-fold decrease in affinity toward four other
      proteins (i.e. lysozyme, trypsinogen, chymotrypsinogen A, and myoglobin) tested
      and this confirmed that the aptamer exhibited a distinct specificity toward
      bovine catalase. This aptamer will be useful in biosensing, Western blot, and
      biomarker identification.

PMID- 22965727
TI  - Qualitative and quantitative evaluation of SimonTM, a new CE-based automated
      Western blot system as applied to vaccine development.
AB  - Many CE-based technologies such as imaged capillary IEF, CE-SDS, CZE, and MEKC
      are well established for analyzing proteins, viruses, or other biomolecules such
      as polysaccharides. For example, imaged capillary isoelectric focusing (charge
      based protein separation) and CE-SDS (size-based protein separation) are standard
      replacement methods in biopharmaceutical industries for tedious and labor
      intensive IEF and SDS-PAGE methods, respectively. Another important analytical
      tool for protein characterization is a Western blot, where after size-based
      separation in SDS-PAGE the proteins are transferred to a membrane and blotted
      with specific monoclonal or polyclonal antibodies. Western blotting analysis is
      applied in many areas such as biomarker research, therapeutic target
      identification, and vaccine development. Currently, the procedure is very manual,
      laborious, and time consuming. Here, we evaluate a new technology called Simple
      WesternTM (or SimonTM) for performing automated Western analysis. This new
      technology is based on CE-SDS where the separated proteins are attached to the
      wall of capillary by a proprietary photo activated chemical crosslink. Subsequent
      blotting is done automatically by incubating and washing the capillary with
      primary and secondary antibodies conjugated with horseradish peroxidase and
      detected with chemiluminescence. Typically, Western blots are not quantitative,
      hence we also evaluated the quantitative aspect of this new technology. We
      demonstrate that SimonTM can quantitate specific components in one of our vaccine
      candidates and it provides good reproducibility and intermediate precision with
      CV <10%.

PMID- 22965733
TI  - Trends in contraceptive use among Florida women: implications for policies and
      programs.
AB  - Our study objective was to assess changes in effective contraceptive use among
      women at risk of unintended pregnancy in Florida in 2008 and 2009 compared with
      2002 and 2004. Contraceptive use questions were available from Florida's
      Behavioral Risk Factor Surveillance System (BRFSS) for both periods (n = 4,606).
      Log binomial regression was used with appropriate methods to account for complex
      sampling in the BRFSS. We examined the change in four effective contraceptive use
      groups: sterilization, long-acting reversible contraceptive (LARC), short-acting
      reversible contraceptive (SARC), and barrier methods. Prevalence ratios comparing
      the two time periods were adjusted by demographic characteristics, employment,
      insurance status, children at home, poverty level, health behaviors, and health
      status. No evidence of change was found in sterilization (Adjusted Prevalence
      Ratio APR = 0.96; 95 % CI: 0.84-1.10) or SARC (APR = 1.01; 95 % CI: 0.87-1.18).
      The overall use of LARC increased and use of barrier methods decreased
      significantly over the two periods (APR = 1.68; 95 % CI: 1.09-2.60 and APR =
      0.77; 95 % CI: 0.61-0.98, respectively). Only two population groups experienced
      significant changes in prevalence in the four use groups over this period. Non
      Hispanic White women increased their use of LARC (APR = 2.89; 95 % CI: 1.58-5.29)
      and women who have never been married decreased their use of barrier methods (APR
      = 0.51; 95 % CI: 0.33-0.77). Contraceptive use in Florida continues to be low
      overall with some shift towards more effective long-term methods. New efforts are
      needed to promote and increase family planning practices, which include the use
      of effective contraceptives.

PMID- 22965734
TI  - Cervical cancer screening in the US-Mexico border region: a binational analysis.
AB  - Cervical cancer mortality is high along the US-Mexico border. We describe the
      prevalence of a recent Papanicolaou screening test (Pap) among US and Mexican
      border women. We analyzed 2006 cross-sectional data from Mexico's National Survey
      of Health and Nutrition and the US Behavioral Risk Factor Surveillance System.
      Women aged 20-77 years in 44 US border counties (n = 1,724) and 80 Mexican border
      municipios (n = 1,454) were studied. We computed weighted proportions for a Pap
      within the past year by age, education, employment, marital status, health
      insurance, health status, risk behaviors, and ethnicity and adjusted prevalence
      ratios (APR) for the US, Mexico, and the region overall. Sixty-five percent (95
      %CI 60.3-68.6) of US women and 32 % (95 %CI 28.7-35.2) of Mexican women had a
      recent Pap. US residence (APR = 2.01, 95 %CI 1.74-2.33), marriage (APR = 1.31, 95
      %CI 1.17-1.47) and insurance (APR = 1.38, 95 %CI 1.22-1.56) were positively
      associated with a Pap test. Among US women, insurance and marriage were
      associated (APR = 1.21, 95 %CI 1.05-1.38 and 1.33, 95 %CI 1.10-1.61,
      respectively), and women aged 20-34 years were about 25 % more likely to have
      received a test than older women. Insurance and marriage were also positively
      associated with Pap testing among Mexican women (APR = 1.39, 95 %CI 1.17-1.64 and
      1.50; 95 %CI 1.23-1.82, respectively), as were lower levels of education (<=8th
      grade or 9th-12th grade versus some college) (APR = 1.74; 95 %CI 1.21-2.52 and
      1.60; 95 %CI 1.03-2.49, respectively). Marriage and insurance were associated
      with a recent Pap test on both sides of the border. Binational insurance coverage
      increases and/or cost reductions might bolster testing among unmarried and
      uninsured women, leading to earlier cervical cancer diagnosis and potentially
      lower mortality.

PMID- 22965736
TI  - Proteomic studies highlight outer-membrane proteins related to biofilm
      development in the marine bacterium Pseudoalteromonas sp. D41.
AB  - Bacterial biofilm development is conditioned by complex processes involving
      bacterial attachment to surfaces, growth, mobility, and exoproduct production.
      The marine bacterium Pseudoalteromonas sp. strain D41 is able to attach strongly
      onto a wide variety of substrates, which promotes subsequent biofilm development.
      Study of the outer-membrane and total soluble proteomes showed ten spots with
      significant intensity variations when this bacterium was grown in biofilm
      compared to planktonic cultures. MS/MS de novo sequencing analysis allowed the
      identification of four outer-membrane proteins of particular interest since they
      were strongly induced in biofilms. These proteins are homologous to a TonB
      dependent receptor (TBDR), to the OmpW and OmpA porins, and to a type IV pilus
      biogenesis protein (PilF). Gene expression assays by quantitative RT-PCR showed
      that the four corresponding genes were upregulated during biofilm development on
      hydrophobic and hydrophilic surfaces. The Pseudomonas aeruginosa mutants unable
      to produce any of the OmpW, OmpA, and PilF homologues yielded biofilms with lower
      biovolumes and altered architectures, confirming the involvement of these
      proteins in the biofilm formation process. Our results indicate that
      Pseudoalteromonas sp. D41 shares biofilm formation mechanisms with human
      pathogenic bacteria, but also relies on TBDR, which might be more specific to the
      marine environment.

PMID- 22965735
TI  - Production of interleukin-27 by human neutrophils regulates their function during
      bacterial infection.
AB  - Septicemia is the most severe form of melioidosis caused by the Gram-negative
      bacterium, Burkholderia pseudomallei. Here, we show that levels of IL-27p28
      transcript and protein were both significantly elevated in patients with sepsis,
      particularly melioidosis and in patients with unfavorable disease outcome.
      Moreover, human monocytes/macrophages and neutrophils were the major source of IL
      27 during infection. The addition of exogenous IL-27 in vitro resulted in
      significantly increased bacterial survival, reduced B. pseudomallei-induced
      oxidative burst, and enhanced IL-1beta and TNF-alpha production by purified
      neutrophils from healthy subjects. Finally, blockade of endogenous IL-27 in
      neutrophils using soluble IL-27 receptor antagonist prior to infection led to
      significantly reduced survival of bacteria and decreased IL-1beta, but not TNF
      alpha production. These results indicate a potential role for IL-27 in the
      suppression of anti-bacterial defense mechanisms that might contribute to disease
      severity in sepsis. The targeting of this cytokine may be beneficial in the
      management of human sepsis.

PMID- 22965737
TI  - Prenatal and perinatal risk factors for attention-deficit/hyperactivity disorder.

PMID- 22965738
TI  - Coregulation of multiple signaling mechanisms in pp60v-Src-induced closure of
      Cx43 gap junction channels.
AB  - Attenuation in gap junctional coupling has consistently been associated with
      induction of rapid or synchronous cell division in normal and pathological
      conditions. In the case of the v-src oncogene, gating of Cx43 gap junction
      channels has been linked to both direct phosphorylation of tyrosines (Y247 and
      265) and phosphorylation of the serine targets of Erk1/2 (S255, 279 and 282) on
      the cytoplasmic C-terminal domain of Cx43. However, only the latter has been
      associated with acute, rather than chronic, gating of the channels immediately
      after v-src expression, a process that is mediated through a "ball-and-chain"
      mechanism. In this study we show that, while ERK1/2 is necessary for acute
      closure of gap junction channels, it is not sufficient. Rather, multiple pathways
      converge to regulate Cx43 coupling in response to expression of v-src, including
      parallel signaling through PKC and MEK1/2, with additional positive and negative
      regulatory effects mediated by PI3 kinase, distinguished by the involvement of
      Akt.

PMID- 22965739
TI  - STEP wastewater treatment: a solar thermal electrochemical process for pollutant
      oxidation.
AB  - A solar thermal electrochemical production (STEP) pathway was established to
      utilize solar energy to drive useful chemical processes. In this paper, we use
      experimental chemistry for efficient STEP wastewater treatment, and suggest a
      theory based on the decreasing stability of organic pollutants (hydrocarbon
      oxidation potentials) with increasing temperature. Exemplified by the solar
      thermal electrochemical oxidation of phenol, the fundamental model and
      experimental system components of this process outline a general method for the
      oxidation of environmentally stable organic pollutants into carbon dioxide, which
      is easily removed. Using thermodynamic calculations we show a sharply decreasing
      phenol oxidation potential with increasing temperature. The experimental results
      demonstrate that this increased temperature can be supplied by solar thermal
      heating. In combination this drives electrochemical phenol removal with enhanced
      oxidation efficiency through (i) a thermodynamically driven decrease in the
      energy needed to fuel the process and (ii) improved kinetics to sustain high
      rates of phenol oxidation at low electrochemical overpotential. The STEP
      wastewater treatment process is synergistic in that it is performed with higher
      efficiency than either electrochemical or photovoltaic conversion process acting
      alone. STEP is a green, efficient, safe, and sustainable process for organic
      wastewater treatment driven solely by solar energy.

PMID- 22965741
TI  - Cyclic side-chain phenylazo naphthalene polymers: enhanced fluorescence emission
      and surface relief grating formation.
AB  - Well-defined cyclic-polymers (cyclic-PAzoMMAs), bearing side-chain phenylazo
      naphthalene chromophore, were successfully synthesized by the combination of atom
      transfer radical polymerization (ATRP) and copper(I)-catalyzed azide/alkyne
      cycloaddition "click" reaction, as verified by GPC, (1) H NMR, FTIR, and MALDI
      TOF mass spectrometry. The cyclic-PAzoMMA showed higher glass transition
      temperatures than the linear-PAzoMMA with the same molecular weight.
      Interestingly, the cyclic-PAzoMMA exhibited deeper modulation depth (M.D.)
      induced by SRG, larger value of the photoinduced birefringence, increased
      fluorescence emission, and longer fluorescence lifetime in comparison with its
      linear counterpart.

PMID- 22965740
TI  - Evaluation of genes involved in limb development, angiogenesis, and coagulation
      as risk factors for congenital limb deficiencies.
AB  - We conducted a population-based case-control study of single nucleotide
      polymorphisms (SNPs) in selected genes to find common variants that play a role
      in the etiology of limb deficiencies (LDs). Included in the study were 389
      infants with LDs of unknown cause and 980 unaffected controls selected from all
      births in New York State (NYS) for the years 1998-2005. We used cases identified
      from the NYS Department of Health (DOH) Congenital Malformations Registry.
      Genotypes were obtained for 132 SNPs in genes involved in limb development (SHH,
      WNT7A, FGF4, FGF8, FGF10, TBX3, TBX5, SALL4, GREM1, GDF5, CTNNB1, EN1, CYP26A1,
      CYP26B1), angiogenesis (VEGFA, HIF1A, NOS3), and coagulation (F2, F5, MTHFR).
      Genotype call rates were >97% and SNPs were tested for departure from Hardy
      Weinberg expectations by race/ethnic subgroups. For each SNP, odds ratios (OR)s
      and confidence intervals (CI)s were estimated and corrected for multiple
      comparisons for all LDs combined and for LD subtypes. Among non-Hispanic white
      infants, associations between FGF10 SNPs rs10805683 and rs13170645 and all LDs
      combined were statistically significant following correction for multiple testing
      (OR = 1.99; 95% CI = 1.43-2.77; uncorrected P = 0.000043 for rs10805683
      heterozygous genotype, and OR = 2.37; 95% CI = 1.48-3.78; uncorrected P = 0.00032
      for rs13170645 homozygous minor genotype). We also observed suggestive evidence
      for associations with SNPs in other genes including CYP26B1 and WNT7A. Animal
      studies have shown that FGF10 induces formation of the apical ectodermal ridge
      and is necessary for limb development. Our data suggest that common variants in
      FGF10 increase the risk for a wide range of non-syndromic limb deficiencies.

PMID- 22965742
TI  - Robot-assisted partial nephrectomy for renal tumors larger than 4 cm: results of
      a multicenter, international series.
AB  - BACKGROUNDS: Limited data are available for the use of robot-assisted partial
      nephrectomy (RAPN) in tumors >4 cm. The objectives of this study were to report
      the perioperative outcomes of a series of patients who underwent RAPN for
      suspicious >4 cm renal tumors and to compare these results with those observed in
      a group of patients with <=4 cm tumors. METHODS: We analyzed retrospectively the
      clinical records of 49 patients who underwent RAPN for suspicious of renal cell
      carcinoma (RCC) >4 cm in size at four centers from September 2008 to September
      2010. All patients underwent da Vinci RAPN. The results were compared with those
      observed in a group of patients undergoing RAPN for <=4 cm renal tumors. RESULTS:
      The median warm ischemia time (WIT) was 22 min (Interquartile range [IQR] 18-28).
      The median console time was 145 min (median IQR 112-177). The median blood loss
      was 120 mL (IQR 62-237). In two cases, we observed intraoperative renal vein
      injury (4 %). Postoperative complications were reported in 13 (26.5 %) patients.
      Major complications were observed in 4 (8.2 %) cases. Patients with large tumors
      showed perioperative outcomes worse than those received the RAPN for <=4 cm
      tumors. Conversely, no significant difference was observed in positive surgical
      margin (PSM) rates. CONCLUSIONS: These outcomes support the use of RAPN as
      possible alternative to open PN for the treatment for patients with suspicious
      renal masses >4 cm. Positive surgical margin rates demonstrated RAPN is an
      oncologically safe procedure for tumors >4 cm.

PMID- 22965743
TI  - Sevoflurane exposure in 7-day-old rats affects neurogenesis, neurodegeneration
      and neurocognitive function.
AB  - OBJECTIVE: Sevoflurane is widely used in pediatric anesthesia and former studies
      showed that it causes neurodegeneration in the developing brain. The present
      study was carried out to investigate the effects of sevoflurane on neurogenesis,
      neurodegeneration and behavior. METHODS: We administered 5-bromodeoxyuridine, an
      S-phase marker, before, during, and after 4 h of sevoflurane given to rats on
      postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade
      staining for degeneration. Spatial reference memory was tested 2 and 6 weeks
      after anesthesia. RESULTS: Sevoflurane decreased progenitor proliferation and
      increased cell death until at least 4 days after anesthesia. Spatial reference
      memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane
      administration. CONCLUSION: Sevoflurane reduces neurogenesis and increases the
      death of progenitor cells in developing brain. This might mediate the late-onset
      neurocognitive outcome after sevoflurane application.

PMID- 22965744
TI  - Correlation of continuous electroencephalogram with clinical assessment scores in
      acute stroke patients.
AB  - OBJECTIVE: To compare electroencephalogram (EEG) symmetry values between stroke
      patients with different 28-day outcomes, and to assess correlations between
      clinical characteristics and 28-day outcomes. METHODS: Twenty-two patients
      presenting with acute ischemic stroke and persistent neurological deficits at EEG
      recording were incrementally included. At 28 days after admission, the modified
      Rankin scale (mRS) was used to evaluate the outcomes, based on which the patients
      were divided into two a posteriori groups, mRS = 6 and mRS <6. Student's t-test
      was used to compare these two groups in terms of brain symmetry index (BSI),
      National Institutes of Health stroke scale (NIHSS), Glasgow coma scale (GCS) and
      acute physiology and chronic health evaluation II (APACHE II) assessed at
      admission. Then EEG parameters, NIHSS, GCS and APACHE II were correlated with the
      mRS. RESULTS: There were significant differences in BSI, NIHSS, GCS, and APACHE
      II between the two groups. Survivors had lower BSI, NIHSS and APACHE II, and
      higher GCS values, compared with patients who died within 28 days after
      admission. Besides, BSI at admission had a positive correlation with mRS at 28
      days (r = 0.441, P = 0.040). NIHSS and APACHE II were also correlated with mRS (r
      = 0.736, P <0.000 1; r = 0.667, P = 0.001, respectively). GCS at admission had a
      negative correlation with mRS (r = -0.656, P = 0.001). CONCLUSION: A higher BSI
      predicts a poorer short-term prognosis for stroke patients. Acute EEG monitoring
      may be of prognostic value for 28-day outcomes. The early prediction of
      functional outcomes after stroke may enhance clinical management and minimize
      short-term mortality.

PMID- 22965745
TI  - Traumatic brain injury increases the risk of female urinary incontinence.
AB  - AIMS: According to our knowledge, no study has attempted to explore the risk of
      urinary incontinence (UI) after traumatic brain injury (TBI). This study aimed to
      examine the relationship between TBI in Taiwanese women and their risk of
      developing UI. METHODS: The study was based on 2,416 female patients newly
      diagnosed with TBI together with 12,080 matched enrollees without a history of
      TBI as a comparison group. All patients were tracked for a 1-year period from
      their index date to identify those who developed subsequent UI. The stratified
      Cox proportional hazards models were performed to compute the risk of UI between
      groups. RESULTS: Of 14,496 patients, 104 (4.30%) from the TBI group and 192
      (1.59%) from the comparison group had a diagnosis of UI during the follow-up
      period. The incidence rate of UI was 4.50 (95% CI: 3.69-5.43) per 100 person
      years in patients with TBI and 1.62 (95% CI: 1.40-1.86) per 100 person-years in
      patients without TBI. The stratified Cox proportional analysis showed that after
      adjusting for socioeconomic status, obesity, hypertension, diabetes, and
      hysterectomy, the increased UI risk of patients with TBI persisted at about the
      same level as in the unadjusted analysis (hazard ratio = 2.78; 95% CI = 2.16
      3.53). In addition, although patients with severe and moderate TBI had higher
      incidence rates of UI than patients with mild TBI, the difference did not reach a
      statistically significant level (P = 0.090). CONCLUSIONS: Our results suggest
      that an increased risk of UI exists at the first year follow-up in patients with
      a TBI diagnosis.

PMID- 22965747
TI  - ATAF2, a NAC transcription factor, binds to the promoter and regulates NIT2 gene
      expression involved in auxin biosynthesis.
AB  - The transcription factor ATAF2, one of the plant specific NAC family genes, is
      known as repressor of pathogenesis-related genes and responsive to the diverse
      defense-related hormones, pathogen infection, and wounding stress. Furthermore,
      it is important to consider that tryptophan-dependant IAA biosynthesis pathway
      can be activated by wounding and pathogen. We found that ATAF2pro::GUS reporter
      was induced upon indole-3-acetonitrile (IAN) treatments. And ataf2 mutant showed
      reduced sensitivity to IAN whereas 35S::ATAF2 plants showed hyper-sensitivity to
      IAN. IAN biosynthesis required nitrilase involved in the conversion of IAN to an
      auxin, indole-3-acetic acid (IAA). We found that the NIT2 gene was repressed in
      ataf2 knockout plants. Expression of both ATAF2 and NIT2 genes was induced by IAN
      treatment. Transgenic plants overexpressing ATAF2 showed up-regulated NIT2
      expression. ATAF2 activated promoter of the NIT2 gene in Arabidopsis protoplasts.
      Electrophoretic mobility shift assay revealed that NIT2 promoter region from
      position -117 to -82 contains an ATAF2 binding site where an imperfect palindrome
      sequence was critical to the protein-DNA interaction. These findings indicate
      that ATAF2 regulates NIT2 gene expression via NIT2 promoter binding.

PMID- 22965746
TI  - Overexpression of a LAM domain containing RNA-binding protein LARP1c induces
      precocious leaf senescence in Arabidopsis.
AB  - Leaf senescence is the final stage of leaf life history, and it can be regulated
      by multiple internal and external cues. La-related proteins (LARPs), which
      contain a well-conserved La motif (LAM) domain and normally a canonical RNA
      recognition motif (RRM) or noncanonical RRM-like motif, are widely present in
      eukaryotes. Six LARP genes (LARP1a-1c and LARP6a-6c) are present in Arabidopsis,
      but their biological functions have not been studied previously. In this study,
      we investigated the biological roles of LARP1c from the LARP1 family.
      Constitutive or inducible overexpression of LARP1c caused premature leaf
      senescence. Expression levels of several senescence-associated genes and defense
      related genes were elevated upon overexpression of LARP1c. The LARP1c null mutant
      1c-1 impaired ABA-, SA-, and MeJA-induced leaf senescence in detached leaves.
      Gene expression profiles of LARP1c showed age-dependent expression in rosette
      leaves. Taken together, our results suggest LARP1c is involved in regulation of
      leaf senescence.

PMID- 22965748
TI  - Development of single-nucleotide polymorphism-based phylum-specific PCR
      amplification technique: application to the community analysis using ciliates as
      a reference organism.
AB  - Despite recent advance in mass sequencing technologies such as pyrosequencing,
      assessment of culture-independent microbial eukaryote community structures using
      universal primers remains very difficult due to the tremendous richness and
      complexity of organisms in these communities. Use of a specific PCR marker
      targeting a particular group would provide enhanced sensitivity and more in-depth
      evaluation of microbial eukaryote communities compared to what can be achieved
      with universal primers. We discovered that many phylum- or group-specific single
      nucleotide polymorphisms (SNPs) exist in small subunit ribosomal RNA (SSU rRNA)
      genes from diverse eukaryote groups. By applying this discovery to a known simple
      allele-discriminating (SAP) PCR method, we developed a technique that enables the
      identification of organisms belonging to a specific higher taxonomic group (or
      phylum) among diverse types of eukaryotes. We performed an assay using two
      complementary methods, pyrosequencing and clone library screening. In doing this,
      specificities for the group (ciliates) targeted in this study in bulked
      environmental samples were 94.6% for the clone library and 99.2% for
      pyrosequencing, respectively. In particular, our novel technique showed high
      selectivity for rare species, a feature that may be more important than the
      ability to identify quantitatively predominant species in community structure
      analyses. Additionally, our data revealed that a target-specific library (or
      ciliate-specific one for the present study) can better explain the ecological
      features of a sampling locality than a universal library.

PMID- 22965750
TI  - Improving the capture of CO2 by substituted monoethanolamines: electronic effects
      of fluorine and methyl substituents.
AB  - The influence of electronic and steric effects on the reaction between CO(2) and
      monoethanolamine (MEA) absorbents is investigated using computational methods.
      The pK(a) of the alkanolamine, the reaction enthalpy for carbamate formation, and
      the hydrolytic carbamate stability are important factors for the efficiency of
      CO(2) capture. The steric and electronic effects of CH(3), CH(2)F, CHF(2), CF(3),
      F, dimethyl, difluoro, and bis(2-trifluoromethyl) substituents at the alpha
      carbon of MEA on this reaction are investigated. Density functional theory (DFT)
      (B3LYP, M06-2X, M08-HX and M11-L) and ab initio methods [spin component-scaled
      second-order Moller-Plesset theory (SCS-MP2), G3], each coupled with solvent
      models [conductor-like polarizable continuum model (CPCM) and universal solvation
      models (SM8 and SMD)], are shown to yield accurately calculated pK(a) values of
      the substituted MEAs. Specifically, G3, SCS-MP2, and M11-L methods coupled with
      the SMD and SM8 solvation models perform well with a mean unsigned error (MUE) of
      only 0.15, 0.24 and 0.25 pK(a) units, respectively. SCS-MP2 is used to calculate
      the reaction enthalpy for carbamate formation and the carbamate stability towards
      hydrolysis. With the introduction of beta-fluoro substituents (especially the
      CH(2) F moiety) the reaction enthalpy for the formation of carbamates can be fine
      tuned to be less exothermic than that using the unsubstituted MEA. This implies a
      reduced energy requirement for the solvent-regeneration step in the post
      combustion carbon-capture method, which is currently the energy-limiting step in
      efficient CO(2) capture. beta-Fluoro-substituted MEAs are also shown to form less
      stable carbamates than MEA. Thus, beta-fluoro-substituted MEAs display a great
      potential for the use in the post-combustion carbon-capture process. Finally, a
      clear correlation is observed between the gas-phase basicity and the tendency to
      form carbamates. This allows for the rapid prediction of which species will be
      formed experimentally, and thus the CO(2)-absorbing capacities of alkanolamines
      can be estimated.

PMID- 22965749
TI  - Increased polyamine biosynthesis enhances stress tolerance by preventing the
      accumulation of reactive oxygen species: T-DNA mutational analysis of Oryza
      sativa lysine decarboxylase-like protein 1.
AB  - A highly oxidative stress-tolerant japonica rice line was isolated by T-DNA
      insertion mutation followed by screening in the presence of 50 mM H(2)O(2). The T
      DNA insertion was mapped to locus Os09g0547500, the gene product of which was
      annotated as lysine decarboxylase-like protein (GenBank accession No. AK062595).
      We termed this gene OsLDC-like 1, for Oryza sativa lysine decarboxylase-like 1.
      The insertion site was in the second exon and resulted in a 27 amino acid N
      terminal deletion. Despite this defect in OsLDC-like 1, the mutant line exhibited
      enhanced accumulation of the polyamines (PAs) putrescine, spermidine, and
      spermine under conditions of oxidative stress. The generation of reactive oxygen
      species (ROS) in the mutant line was assessed by qRT-PCR analysis of NADPH
      oxidase (RbohD and RbohF), and by DCFH-DA staining. Cellular levels of ROS in
      osldc-like 1 leaves were significantly lower than those in the wild-type (WT)
      rice after exposure to oxidative, high salt and acid stresses. Exogenously
      applied PAs such as spermidine and spermine significantly inhibited the stress
      induced accumulation of ROS and cell damage in WT leaves. Additionally, the
      activities of ROS-detoxifying enzymes were increased in the homozygous mutant
      line in the presence or absence of H(2)O(2). Thus, mutation of OsLDC-like 1
      conferred an oxidative stress-tolerant phenotype. These results suggest that
      increased cellular PA levels have a physiological role in preventing stress
      induced ROS and ethylene accumulation and the resultant cell damage.

PMID- 22965751
TI  - Effect of growing location, malaxation duration and citric acid treatment on the
      quality of olive oil.
AB  - BACKGROUND: The total phenolic compounds of olive oil exert antiradical activity
      at cellular level and can prevent cardiovascular disease, metabolic syndrome and
      cancer. Increased awareness of its health benefits has increased the consumption
      of olive oil around the world. An alternative processing technique effective in
      increasing the amount of oil extracted while maintaining the oil quality is
      needed to meet the rising global demand for olive oil. RESULTS: Addition of 0.3 g
      mL(-1) citric acid at 1:1000 (v/w) to olive paste followed by a 30 min malaxation
      period significantly increased the oil recovery, concentration of total phenolic
      compounds and antiradical activity by 46.23, 120.27 and 31.48% respectively.
      While there was no significant effect on the acidity, the peroxide value was
      significantly reduced by 63.85%. The organoleptic characteristics of the olive
      oil extracted with citric acid were also comparable to those of the control.
      CONCLUSION: Addition of 0.3 g mL(-1) citric acid (i.e. 30% w/v) at 1:1000 (v/w)
      to olive paste followed by a 30 min malaxation period in a Blixer((r)) 4.0
      blender is the most promising extraction technique to improve the oil recovery,
      concentration of total phenolic compounds and antiradical activity of the
      extracted olive oil without compromising other quality parameters.

PMID- 22965752
TI  - Kinetics of growth and ethanol formation from a mix of glucose/xylose substrate
      by Kluyveromyces marxianus UFV-3.
AB  - The fermentation of both glucose and xylose is important to maximize ethanol
      yield from renewable biomass feedstocks. In this article, we analyze growth,
      sugar consumption, and ethanol formation by the yeast Kluyveromyces marxianus UFV
      3 using various glucose and xylose concentrations and also under conditions of
      reduced respiratory activity. In almost all the conditions analyzed, glucose
      repressed xylose assimilation and xylose consumption began after glucose had been
      exhausted. A remarkable difference was observed when mixtures of 5 g L(-1)
      glucose/20 g L(-1) xylose and 20 g L(-1) glucose/20 g L(-1) xylose were used. In
      the former, the xylose consumption began immediately after the glucose depletion.
      Indeed, there was no striking diauxic phase, as observed in the latter condition,
      in which there was an interval of 30 h between glucose depletion and the
      beginning of xylose consumption. Ethanol production was always higher in a
      mixture of glucose and xylose than in glucose alone. The highest ethanol
      concentration (8.65 g L(-1)) and cell mass concentration (4.42 g L(-1)) were
      achieved after 8 and 74 h, respectively, in a mixture of 20 g L(-1) glucose/20 g
      L(-1) xylose. When inhibitors of respiration were added to the medium, glucose
      repression of xylose consumption was alleviated completely and K. marxianus was
      able to consume xylose and glucose simultaneously.

PMID- 22965753
TI  - The evolution of actinomycetes: papers from the 16th International Symposium on
      the Biology of Actinomycetes.

PMID- 22965754
TI  - Updating the taxonomic toolbox: classification of Alteromonas spp. using
      multilocus phylogenetic analysis and MALDI-TOF mass spectrometry.
AB  - Bacteria of the genus Alteromonas are Gram-negative, strictly aerobic, motile,
      heterotrophic marine bacteria known for their versatile metabolic activities.
      Identification and classification of novel species belonging to the genus
      Alteromonas generally involves DNA-DNA hybridization (DDH) as distinct species
      often fail to be resolved at the 97 % threshold value of the 16S rRNA gene
      sequence similarity. In this study, the applicability of Multilocus Phylogenetic
      Analysis (MLPA) and Matrix-Assisted Laser Desorption Ionization Time-of-Flight
      Mass Spectrometry (MALDI-TOF MS) for the differentiation of Alteromonas species
      has been evaluated. Phylogenetic analysis incorporating five house-keeping genes
      (dnaK, sucC, rpoB, gyrB, and rpoD) revealed a threshold value of 98.9 % that
      could be considered as the species cut-off value for the delineation of
      Alteromonas spp. MALDI-TOF MS data analysis reconfirmed the Alteromonas species
      clustering. MLPA and MALDI-TOF MS both generated data that were comparable to
      that of the 16S rRNA gene sequence analysis and may be considered as useful
      complementary techniques for the description of new Alteromonas species.

PMID- 22965755
TI  - Associations among imaging measures (2): the association between gray matter
      concentration and task-induced activation changes.
AB  - The association between functional activation and gray matter (GM) structure has
      been revealed in clinical studies and studies of aging involving a small number
      of subjects. The purpose of this study was to investigate the association between
      functional activation maps and GM structures in young adults who do not show
      apparent GM atrophy and to investigate in detail the nature of this association
      using a large number of subjects. We used voxel-by-voxel regression analyses to
      investigate voxel-by-voxel associations between GM concentration (GMC) and
      contrast estimate images of brain activity during n-back working memory tasks.
      Associations were assessed for each voxel after regressing out the effects of
      age, sex, and mean signal intensity during functional magnetic resonance imaging
      scanning at each voxel using data from 248 normal, right-handed, young adult
      subjects. In our study, the concept of "the greater the GMC, the greater the task
      related activation increase/task-related activation decrease (or the greater the
      task-related activation change from baseline)" was true for a wide range of
      activated and deactivated areas. However, in some minor regions, the other
      pattern of "the greater the GMC, the smaller the task-related activation
      increase" was observed. The first pattern is often observed at the borders of GM
      structures. These findings may have to be taken into consideration when
      group/individual differences in functional activation are investigated.

PMID- 22965756
TI  - Results after U-shaped pectoralis major myocutaneous flap reconstruction of
      circumferential pharyngeal defects.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate surgical, functional, carcinologic results
      after circumferential pharyngolaryngectomy and reconstruction with U-shaped
      pectoralis major myocutaneous flap. STUDY DESIGN: Retrospective case series.
      METHODS: Forty-one patients included spanning a 6-year period. RESULTS: General
      and local complications occurred in 10% and 22% of patients respectively, without
      early death. Swallowing and vocal functions were satisfactory for 82% and 43% of
      patients respectively, despite 39% of neopharynx stricture and 22% of
      pharyngocutaneous fistula. With a 20-month mean follow-up, cancer recurrence was
      present in 58% of patients. The overall survival rate was 29% at 3 years.
      CONCLUSIONS: This flap is simple, reliable, and allows adequate reconstruction of
      the hypopharynx. However, the neopharynx stricture rate is high and the quality
      of voice rehabilitation is poor when compared with free flaps. This procedure,
      which is an option for the reconstruction of circumferential pharyngeal defects,
      must be considered in selected cases.

PMID- 22965757
TI  - Decreased plasma cholesterol concentrations after PUFA-rich diets are not due to
      reduced cholesterol absorption/synthesis.
AB  - Plasma cholesterol concentrations increase with consumption of high saturated
      fatty acid (SFA) and decrease with high polyunsaturated fatty acid (PUFA) diets,
      leading to shifts in lipid levels consistent with reduction in heart disease
      risk. Direct measurements of cholesterol absorption, one of the key regulators of
      plasma cholesterol levels, have not been performed in humans after consumption of
      high PUFA diets. Thus, cholesterol absorption and fractional synthesis rates
      (FSRs) were measured in 16 healthy adults (8 males and 9 females) using a
      randomized cross-over study with a diet containing high (PUFA/SFA) P/S ratio
      (2:1) and a low P/S ratio (0.5:1). Cholesterol absorption and fractional
      cholesterol synthetic rates were measured using stable isotopes after 20 days of
      dietary intervention. Diet did not affect cholesterol absorption or synthesis.
      There was a significant decrease in plasma cholesterol concentrations (P < 0.02),
      specifically LDL-cholesterol (P < 0.02), without a change in HDL-cholesterol or
      triacylglycerol concentrations. Intraluminal cholesterol solubilization and
      plasma sterol (cholesterol biosynthetic intermediates and plant sterols) levels
      were not affected by diet. Thus, consumption of diets with a high P/S ratio
      reduces plasma total and LDL-cholesterol concentrations independent of shifts in
      cholesterol absorption or synthesis.

PMID- 22965758
TI  - Lipocalin-2 ameliorates granulocyte functionality.
AB  - Attraction of neutrophils to sites of infection or tissue injury is an essential
      prerequisite for an efficient innate immune response. Herein, we provide novel
      evidence that the antimicrobial protein, neutrophil gelatinase associated
      lipocalin (24p3 or lipocalin-2, Lcn2) is a central regulator of this process.
      Lcn2 is produced by several cell types but high amounts are released by
      neutrophils. Using human and murine neutrophils, we found that the addition of
      recombinant Lcn2 significantly stimulated their migration, which was independent
      of IL-8/keratinocyte chemokine formation. Mechanistically, this could be traced
      back to Lcn2-mediated changes of Erk1/2 signaling. Accordingly, the i.p.
      injection of Lcn2 into C57BL/6 mice stimulated the mobilization of neutrophils
      while we found a significantly reduced neutrophil chemotactic activity of cells
      obtained from Lcn2 KO mice. This observation transmitted to a reduced
      accumulation of neutrophils in intra-dermal lesions infected with Salmonella
      typhimurium in Lcn2 KO mice as compared to WT mice. This was not only due to a
      reduced chemotaxis but also to an impaired cellular adhesion of neutrophils in
      the absence of Lcn2. We herein describe a novel role of Lcn2 as an important
      paracrine chemoattractant and an indispensable factor for neutrophil function in
      inflammation.

PMID- 22965759
TI  - Storage-induced changes of the cytosolic red blood cell proteome analyzed by 2D
      DIGE and high-resolution/high-accuracy MS.
AB  - The storage of packed red blood cells (RBCs) is associated with the development
      of morphological and biochemical changes leading to a reduced posttransfusion
      functionality and viability of the cells. Within this study, 2D DIGE and high
      resolution/high-accuracy Orbitrap MS were used to analyze the storage-induced
      changes of the cytosolic RBC proteome and identify characteristic protein
      patterns and potential marker proteins for the assessment of RBC storage lesions.
      Leukodepleted RBC concentrates were stored according to standard blood bank
      conditions for 0, 7, 14, 28, and 42 days and analyzed by using a characterized
      and validated protocol. Following statistical evaluation, a total of 14 protein
      spots were found to be significantly altered after 42 days of ex vivo storage.
      Protein identification was accomplished by tryptic digestion and LC-MS/MS and
      three proteins potentially useful as biomarkers for RBC aging comprising
      transglutaminase 2, beta actin, and copper chaperone for superoxide dismutase
      were selected and validated by western blot analysis. These can serve as a basis
      for the development of a screening assay to detect RBC storage lesions and
      autologous blood doping in sports.

PMID- 22965760
TI  - Stuffer-free multiplex ligation-dependent probe amplification based on
      conformation-sensitive capillary electrophoresis: a novel technology for robust
      multiplex determination of copy number variation.
AB  - Developing diagnostic tools based on the application of known disease/phenotype
      associated copy number variations (CNVs) requires the capacity to measure CNVs in
      a multiplex format with sufficient reliability and methodological simplicity. In
      this study, we developed a reliable and user-friendly multiplex CNV detection
      method, termed stuffer-free MLPA-CE-SSCP, that combines a variation of multiplex
      ligation-dependent probe amplification (MLPA) with CE-SSCP. In this variation,
      MLPA probes were designed without the conventionally required stuffer sequences.
      To separate the similar-sized stuffer-free MLPA products, we adopted CE-SSCP
      rather than length-dependent conventional CE analysis. An examination of the
      genomic DNA from five cell lines known to vary in X-chromosome copy number (1-5)
      revealed that copy number determinations using stuffer-free MLPA-CE-SSCP were
      more accurate than those of conventional MLPA, and the CV of the measured copy
      numbers was significantly lower. Applying our system to measure the CNVs on
      autosomes between two HapMap individuals, we found that all peaks for CNV targets
      showed the expected copy number changes. Taken together, our results indicate
      that this new strategy can overcome the limitations of conventional MLPA, which
      are mainly related to long probe length and difficulties of probe preparation.

PMID- 22965761
TI  - Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones.
AB  - Signal transducers and activators of transcription (STATs) are the final
      "switches" that activate gene expression patterns that lead to human malignancy.
      Extracellular signal-regulated kinases (ERK 1/2) activate STAT 3; four
      cardiovascular hormones inhibit ERK 1/2 kinases, leading to the hypothesis that
      they may also inhibit STATs. These four cardiac hormones, i.e., vessel dilator,
      long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial
      natriuretic peptide (ANP), eliminate human cancers growing in mice. These four
      cardiac hormones' effects on STATs 1 and 3 were examined in human small-cell lung
      cancer and human pancreatic adenocarcinoma cells. Vessel dilator, LANP,
      kaliuretic peptide, and ANP maximally decreased STAT 3 by 88, 54, 55, and 65 %,
      respectively, at their 1 MUM concentrations in human small-cell lung cancer cells
      and STAT 3 by 66, 57, 70, and 77 % in human pancreatic adenocarcinoma cells,
      respectively. The cardiac hormones (except LANP) also significantly decreased
      STAT 3 measured by Western blots. These cardiac hormones did not decrease STAT 1
      in either human small-cell lung cancer or pancreatic adenocarcinoma cells. We
      conclude that these four cardiac hormones are significant inhibitors of STAT 3,
      but not STAT 1, in human small-cell lung cancer and pancreatic adenocarcinoma
      cells, which suggests a specificity for these hormones' anticancer mechanism(s)
      of action enzymology in human cancer cells.

PMID- 22965762
TI  - DNA-based programing of quantum dot properties.
AB  - Nucleic acid molecules can serve as robust ligands for aqueous synthesis of
      semiconductor nanocrystals or quantum dots (QDs). QD properties including size,
      morphology, dispersity, emission maximum, and quantum yield are highly dependent
      on the sequences and structures of nucleic acids used for the synthesis. This
      synthetic strategy provides a novel facile means of constructing compact, stable,
      and biofunctionalized QDs in one step, which is of particular interest for a
      variety of applications such as biosensing, bioimaging, and self-assembly. This
      article summarizes recent advances in nucleic acid-templated QD synthesis with an
      emphasis on the nucleic acids-based programing of quantum dots properties. A
      variety of applications based on DNA-passivated QDs are also discussed.

PMID- 22965763
TI  - Synthesis of Novel Core Cross-Linked Star-Based Polyrotaxane End-Capped via
      "CuAAC" Click Chemistry.
AB  - The first example of core cross-linked star (CCS) polyrotaxane was prepared using
      the poly(epsilon-caprolactone) (PCL) CCS three-dimensional (3D) scaffold. The 3D
      CCS polymer was firstly prepared through the "arm-first" approach. Then, the
      "arms" of the resultant PCL CCS polymer were threaded with alpha-cyclodextrins
      (alpha-CDs). The threaded alpha-CDs were permanently locked by the "click"
      reaction of terminal alkyne functionalities of the star polymers with the azide
      functionalized end caps to afford the CCS polyrotaxanes. All analytical results
      confirm the formation of the CCS polyrotaxanes and reveal their characteristics,
      including fluorescence under UV, a channel-type crystalline structure, a two-step
      thermal decomposition, and a unique core-shell structure in great contrast to the
      polymer precursors. 

PMID- 22965764
TI  - Duplication of OCRL and adjacent genes associated with autism but not Lowe
      syndrome.
AB  - Disturbances in the form of microduplications and microdeletions have been found
      throughout the genome and have been associated with autism, intellectual
      disability, and recognizable malformation syndromes. In our study of 187 probands
      with autism, we have identified a duplication in Xq25 including full gene
      duplication of OCRL and six flanking genes. Activity of the enzyme gene product
      in fibroblasts was elevated to over twice the level in control fibroblasts. The
      boy had no somatic or neurological findings reminiscent of Lowe syndrome.

PMID- 22965765
TI  - Assessment of ventricular functions by tissue Doppler echocardiography in
      children with asthma.
AB  - Patients with asthma develop pulmonary hypertension due to recurrent hypoxia and
      chronic inflammation, leading to right heart enlargement with ventricular
      hypertrophy. Patients with severe asthma can experience cor pulmonale later in
      life, but little is known about ventricular function during the early stages of
      the disease. This study aimed to investigate ventricular functions in
      asymptomatic children with asthma as detected by conventional echocardiography
      and tissue Doppler echocardiography (TDE). Fifty-one pediatric patients (mean age
      10.4 +/- 2.2 years) with asthma and 46 age- and sex-matched healthy children
      (mean age 10.9 +/- 2.4 years) were studied. All subjects were examined by
      conventional echocardiography and TDE, and they had pulmonary function tests on
      spirometry. The right-ventricular (RV) wall was statistically (p = 0.01) thicker
      among asthmatic patients (4.7 +/- 1.5 mm) compared with healthy children (3.6 +/-
      0.4 mm). However, conventional pulsed-Doppler indices of both ventricles did not
      differ significantly between asthmatic patients and healthy children (p > 0.05).
      The results of TDE examining RV diastolic function showed that annular peak
      velocity during early diastole (E'), annular peak velocity during late diastole
      (A') (16.4 +/- 1.8 and 5.1 +/- 1.4 cm/s, respectively), E'/A' ratio (3.2 +/-
      0.7), isovolumetric relaxation time (67.7 +/- 10.2 ms) and myocardial performance
      index (48.1 % +/- 7.0 %) of the lateral tricuspid annulus among asthmatic
      patients differed significantly (p = 0.01) from those of healthy children (13.2
      +/- 2.3, 8.2 +/- 2.0 cm/s, 1.6 +/- 0.5, 46.2 +/- 8.7 ms, and 42.0 % +/- 5.7 %,
      respectively). Only peak expiratory flow (PEF) rate from the pulmonary function
      tests was negatively correlated with the E'/A' ratio of the tricuspid annulus (r
      = -0.38, p = 0.01). This study showed that although the findings of clinical and
      conventional echocardiography were apparently normal in children with asthma, TDE
      showed subclinical dysfunction of the right ventricle, which is negatively
      correlated with PEF. These findings signify the diagnostic value of TDE in the
      early detection and monitoring of such deleterious effects among asthmatic
      patients.

PMID- 22965766
TI  - American Academy of Pediatrics sedation guidelines: are we there yet?

PMID- 22965767
TI  - pH Impedance and high-resolution manometry in laryngopharyngeal reflux disease
      high-dose proton pump inhibitor failures.
AB  - OBJECTIVES/HYPOTHESIS: Laryngopharyngeal reflux disease (LPRD) patients often
      fail empiric treatment with high-dose, twice-daily (BID) proton pump inhibitors
      (PPIs). Further testing is warranted to rule in or out nonacid reflux (NAR) or
      breakthrough acid reflux (BAR) as the etiology of the symptoms. Results of
      coordinated multichannel intraluminal pH impedance (MII) and high-resolution
      esophageal manometry (HRM) testing while patients are on high-dose BID PPIs is
      lacking in the LPRD population. The objective of this study is to evaluate if
      coordinated MII and HRM aid in the management of patients with persistent LPRD
      symptoms despite high dose BID PPIs. STUDY DESIGN: Retrospective case series.
      METHODS: MII and HRM were administered while on medication to 23 persistent LPRD
      subjects who had failed 3 months of high-dose BID PPIs. Number and pH of total
      and proximal reflux episodes, DeMeester score, reflux symptom correlation, and
      motility/physiology findings were recorded. Subjects were grouped into
      significant NAR, BAR, or nonsignificant NAR. RESULTS: Fifty-two percent of
      subjects had significant NAR and 22% had BAR despite high-dose BID PPIs.
      Statistically significant differences were found between groups for the MII
      outcomes of DeMeester score, number of total and proximal reflux events, and
      nonacid reflux events. HRM demonstrated dysmotility in five subjects.
      CONCLUSIONS: For recalcitrant LPRD subjects who fail empiric high-dose BID PPI
      therapy, this study demonstrated significant NAR or BAR in 74% of subjects.
      Evaluation by MII and HRM performed on PPI therapy proved useful for diagnosis
      and further management.

PMID- 22965768
TI  - Addressing sexual problems in HIV primary care: experiences from patients.
AB  - Evidence suggests that sexual problems are common among people living with HIV
      and may be related to sexual risk taking and treatment adherence. This study
      explored the extent to which sexual problems experienced by people with HIV are
      addressed in primary care as well as how primary care responses to sexual
      problems are experienced by patients. Structured interviews were conducted with
      60 patients at an urban HIV clinic. The average age of the participants (37 male,
      23 female) was 45.8 years (SD = 7.9). Sexual problems were common. The most
      common sexual problem experienced in the past year was a lack of interest in sex
      (53.3 % reported) and the least common problem was painful intercourse (reported
      by 20 %). There were no gender differences in reports of sexual problems, except
      that painful intercourse was more frequently reported by women than men.
      Relatively few individuals who experienced sexual problems had discussed them
      with their provider, but these individuals were generally pleased with the
      counseling they had received and could identify several factors that facilitated
      a positive patient-provider interaction. Those who offer primary care services to
      people with HIV should be aware of sexual problems their patients may be
      experiencing and should feel confident in their ability to successfully address
      these problems. Providers may need additional training in order to adequately
      address sexual problems among people with HIV in primary care settings.

PMID- 22965769
TI  - Human finger somatotopy in areas 3b, 1, and 2: a 7T fMRI study using a natural
      stimulus.
AB  - To study the properties of human primary somatosensory (S1) cortex as well as its
      role in cognitive and social processes, it is necessary to noninvasively localize
      the cortical representations of the body. Being arguably the most relevant body
      parts for tactile exploration, cortical representations of fingers are of
      particular interest. The aim of the present study was to investigate the cortical
      representation of individual fingers (D1-D5), using human touch as a stimulus.
      Utilizing the high BOLD sensitivity and spatial resolution at 7T, we found that
      each finger is represented within three subregions of S1 in the postcentral
      gyrus. Within each of these three areas, the fingers are sequentially organized
      (from D1 to D5) in a somatotopic manner. Therefore, these finger representations
      likely reflect distinct activations of BAs 3b, 1, and 2, similar to those
      described in electrophysiological work in non-human primates. Quantitative
      analysis of the local BOLD responses revealed that within BA3b, each finger
      representation is specific to its own stimulation without any cross-finger
      responsiveness. This finger response selectivity was less prominent in BA 1 and
      in BA 2. A test-retest procedure highlighted the reproducibility of the results
      and the robustness of the method for BA 3b. Finally, the representation of the
      thumb was enlarged compared to the other fingers within BAs 1 and 2. These
      findings extend previous human electrophysiological and neuroimaging data but
      also reveal differences in the functional organization of S1 in human and
      nonhuman primates.

PMID- 22965770
TI  - Pulmonary sequestration with haemoptysis and an unsuspected carcinoid tumour.
AB  - We report the case of a fit and healthy 41-year-old man, who presented with
      significant haemoptysis without a history of recurrent infections. His computed
      tomography scan showed a dense lesion in the left lower lobe with a feeding
      vessel arising from the abdominal aorta, characteristic for an intra-pulmonary
      sequestration. To prevent possible further haemoptysis or infections, a left
      lower lobectomy was performed. The histological examination showed the typical
      features of a sequestration. However, within the sequestration, a carcinoid
      tumour without atypical features was found. There was no lymph node involvement.
      Sequestrations are congenital lesions without communication with the bronchial
      tree and with a systemic blood supply. They commonly cause recurrent infection.
      Fatal haemoptysis has also been described, but is rare. There are very few
      reports of neoplastic lesions in sequestrations. This case illustrates two
      unusual aspects of sequestrations. Surgery offers definitive treatment for both
      pathologies, as opposed to embolisation. 

PMID- 22965771
TI  - Spatiotemporal analysis of vocal fold vibrations between children and adults.
AB  - OBJECTIVES/HYPOTHESIS: Aim of the study is to quantify differences in
      spatiotemporal features of vibratory motion in typically developing prepubertal
      children and adults with use of high speed digital imaging. STUDY DESIGN:
      Prospective case-control study. METHODS: Vocal fold oscillations of 31 children
      and 35 adults were analyzed. Endoscopic high-speed imaging was performed during
      sustained phonation at typical pitch and loudness. Quantitative technique of
      Phonovibrogram was used to compute spatiotemporal features. Spatial features are
      represented by opening and closing angles along the anterior and posterior parts
      of the vocal folds, as well as by left-right symmetry ratio. Temporal features
      are represented by the cycle-to-cycle variability of the spatial features. Group
      differences (adult females, adult males, and children) were statistically
      investigated. RESULTS: Statistical differences were more pronounced in the
      temporal behavior compared to the spatial behavior. Children demonstrated greater
      cycle-to-cycle variability in oscillations compared to adults. Most differences
      between children and adults were found for temporal characteristics along the
      anterior parts during closing phase. The spatiotemporal features differed more
      between children and males than between children and females. Both adults and
      children showed equally high left-right symmetry. CONCLUSIONS: Results suggest a
      more unstable phonation in children than in adults, yielding increased
      perturbation in periodicity. Children demonstrated longer phase delay in the
      anterior/posterior and medio-lateral parts during the opening phase compared to
      adults. The data presented may provide the bases for differentiating normal
      vibratory characteristics from the disordered in the pediatric population, and
      eventually assist in aiding the clinical utility of high speed imaging.

PMID- 22965772
TI  - Treatment strategy for intracranial primary pure germinoma.
AB  - OBJECT: This prospective randomized clinical study will address the efficacy of
      radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and
      propose the novel standard treatment strategy for intracranial primary pure
      germinoma. MATERIALS AND METHODS: Between 2005 and 2008, there were 54 patients
      diagnosed with intracranial primary pure germinomas in a single institute. Twenty
      eight patients were enrolled. The mean age of the patients was 16.2 years (range
      6-31 years). There were 19 men and 9 women (men/women ratio = 2.1:1). There were
      21 patients with solitary tumors and 7 with multiple tumors. These patients were
      randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and
      combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by
      response-adapted RT) treatment group. The follow-up period for RT only group has
      a median of 58 months (mean 58.2 months, range 41-82 months), and for combine
      therapy group, the median was 68.5 months (mean 67.8 months, range 41-88 months).
      All 14 patients in the RT-only group showed complete response (CR) and no
      recurrence. Eleven patients in the combined group had CR and three patients had
      partial response after neo-adjuvant CTX. All patients responded to RT as CR
      without recurrence. At the time of analysis, all 28 patients were alive without
      evidence of disease. CONCLUSION: Neo-adjuvant CTX for localized germinomas seems
      to be unnecessary as a method to reduce radiation dose in our RT protocol.
      However, the effective control of multifocal or disseminated germinoma can be
      achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.

PMID- 22965773
TI  - A new nonsense mutation in the NF1 gene with neurofibromatosis-Noonan syndrome
      phenotype.
AB  - PURPOSE: Neurofibromatosis-Noonan syndrome is a rare autosomal dominant disorder
      which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1
      gene mutations are reported in the majority of these patients. METHOD: Sequence
      analysis of the established genes for Noonan syndrome revealed no mutation; a
      heterozygous NF1 point mutation c.7549C>T in exon 51, creating a premature stop
      codon (p.R2517X), had been demonstrated. RESULT: Neurofibromatosis-Noonan
      syndrome recently has been considered a subtype of NF1 and caused by different
      NF1 mutations. CONCLUSION: We report the case of a 14-year-old boy with
      neurofibromatosis type 1 with Noonan-like features, who complained of headache
      with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T
      in exon 51.

PMID- 22965774
TI  - Gabriele Fallopio (1523-1562) and his contributions to the development of
      medicine and anatomy.
AB  - INTRODUCTION: Gabriele Fallopio was one of the greatest anatomists of the
      sixteenth century. He discovered and named numerous parts of the human body. His
      name survives to this day as it is associated with several anatomical structures
      including the Fallopian canal, Fallopian hiatus, Fallopian valve, Fallopian
      muscle, and the Fallopian tube. CONCLUSIONS: Our current knowledge of human
      anatomy is based on giants such as Fallopio. His contributions to neuroanatomy
      laid the foundations for the development of this discipline.

PMID- 22965775
TI  - Penile alterations with severe sperm abnormalities in antiphospholipid syndrome
      associated with systemic lupus erythematosus.
AB  - This study aims to perform global gonadal and sexual function assessments in
      systemic lupus erythematosus-related antiphospholipid syndrome (SLE-APS)
      patients. A cross-sectional study was conducted in ten SLE-APS male patients and
      20 healthy controls. They were assessed by demographic data, clinical features,
      urological examination, sexual function, testicular ultrasound, seminal
      parameters, sperm antibodies, and hormone profile. The median of current age was
      similar in SLE-APS patients and controls with a higher frequency of erectile
      dysfunction in the former group (30 vs. 0 %, p = 0.029). The median penis
      circumference was significantly reduced in SLE-APS patients with erectile
      dysfunction compared to patients without this complication (8.17 vs. 9.14 cm, p =
      0.0397). SLE-APS patients with previous arterial thrombosis had a significantly
      reduced median penis circumference compared to those without this complication
      (7.5 vs. 9.18 cm, p = 0.039). Comparing SLE-APS patients and controls, the former
      had a significant lower median of sperm concentration (41.1 vs. 120.06 *
      10(6)/mL, p = 0.003), percentages of sperm motility (47.25 vs. 65.42 %, p =
      0.047), normal sperm forms by WHO guidelines (11 vs. 23.95 %, p = 0.002), and
      Kruger criteria (2.65 vs. 7.65 %, p = 0.02). Regarding seminal analysis, the
      medians of sperm concentration and total sperm count were significantly lower in
      SLE-APS patients treated with intravenous cyclophosphamide vs. those untreated
      with this drug (p < 0.05). Therefore, we have observed a novel association of
      reduced penile size with erectile dysfunction and previous arterial thrombosis in
      SLE-APS patients. Penis assessment should be routinely done in SLE-APS patients
      with fertility problems. We also identified that intravenous cyclophosphamide
      underlies severe sperm alterations in these patients.

PMID- 22965776
TI  - Health-related quality of life in young adult patients with rheumatoid arthritis
      in Iran: reliability and validity of the Persian translation of the PedsQLTM 4.0
      Generic Core Scales Young Adult Version.
AB  - The objective of the present study was to determine the reliability and validity
      of the Persian translation of the Pediatric Quality of Life Inventory (PedsQLTM)
      4.0 Generic Core Scales Young Adult Version in an Iranian sample of young adult
      patients with rheumatoid arthritis (RA). One hundred ninety-seven young adult
      patients with RA completed the 23-item PedsQLTM and the 36-item Short-Form Health
      Survey (SF-36). Disease activity based on Disease Activity Score 28 was also
      measured. Internal consistency and test-retest reliability, as well as construct,
      discriminant, and convergent validity, were tested. Confirmatory factor analysis
      (CFA) was used to verify the original factor structure of the PedsQLTM. Also,
      responsiveness to change in PedsQLTM scores over time was assessed. Cronbach's
      alpha coefficients ranged from alpha = 0.82 to alpha = 0.91. Test-retest
      reproducibility was satisfactory for all scales and the total scale score. The
      PedsQL proved good convergent validity with the SF-36. The PedsQL distinguished
      well between young adult patients and healthy young adults and also RA groups
      with different comorbidities. The CFA did not confirm the original four-factor
      model, instead, analyses revealed a best-fitting five-factor model for the
      PedsQLTM Young Adult Version. Repeated measures analysis of variance indicated
      that the PedsQL scale scores for young adults increased significantly over time.
      The Persian translation of the PedsQLTM 4.0 Generic Core Scales Young Adult
      Version demonstrated good psychometric properties in young adult patients with RA
      and can be recommended for the use in RA research in Iran.

PMID- 22965777
TI  - Drosophila LSD1-CoREST demethylase complex regulates DPP/TGFbeta signaling during
      wing development.
AB  - The choice and timing of specific developmental pathways in organogenesis are
      determined by tissue-specific temporal and spatial cues that are acted upon to
      impart unique cellular and compartmental identities. A consequence of cellular
      signaling is the rapid transcriptional reprogramming of a wide variety of target
      genes. To overcome intrinsic epigenetic chromatin barriers to transcription
      modulation, histone modifying and remodeling complexes are employed. The
      deposition or erasure of specific covalent histone modifications, including
      acetylation, methylation, and ubiquitination are essential features of gene
      activation and repression. We have found that the activity of a specific class of
      histone demethylation enzymes is required for the specification of vein cell
      fates during Drosophila wing development. Genetic tests revealed that the
      Drosophila LSD1-CoREST complex is required for proper cell specification through
      regulation of the DPP/TGFbeta pathway. An important finding from this analysis is
      that LSD1-CoREST functions through control of rhomboid expression in an EGFR
      independent pathway.

PMID- 22965778
TI  - Optimal timing of noncardiac surgery after stents.

PMID- 22965780
TI  - Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS):
      what have we learned and what will we learn?

PMID- 22965779
TI  - Contraception in patients with heart failure.

PMID- 22965781
TI  - Radiation dermatitis.

PMID- 22965782
TI  - Femoral pseudoaneurysm with a communicating arteriovenous fistula: a complication
      after percutaneous coronary intervention.

PMID- 22965784
TI  - Letter by Fort and Plachetka regarding article, "association of proton pump
      inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor:
      insights from PLATO".

PMID- 22965785
TI  - Influence of congenital human cytomegalovirus infection and the NKG2C genotype on
      NK-cell subset distribution in children.
AB  - Human cytomegalovirus (HCMV) has been reported to reshape the NK-cell receptor
      (NKR) distribution, promoting an expansion of CD94/NKG2C(+) NK and T cells. The
      role of NK cells in congenital HCMV infection is ill-defined. Here we studied the
      expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the
      NKG2C gene deletion in children with past congenital infection, both symptomatic
      (n = 15) and asymptomatic (n = 11), including as controls children with postnatal
      infection (n = 11) and noninfected (n = 20). The expansion of NKG2C(+) NK cells
      in HCMV-infected individuals appeared particularly marked and was associated with
      an increased number of LILRB1(+) NK cells in cases with symptomatic congenital
      infection. Increased numbers of NKG2C(+), NKG2A(+), and CD161(+) T cells were
      also associated to HCMV infection. The NKG2C deletion frequency was comparable in
      children with congenital HCMV infection and controls. Remarkably, the homozygous
      NKG2C(+/+) genotype appeared associated with increased absolute numbers of
      NKG2C(+) NK cells. Moreover, HCMV-infected NKG2C(+/+) children displayed higher
      absolute numbers of NKG2A(+) and total NK cells than NKG2C(+/-) individuals. Our
      study provides novel insights on the impact of HCMV infection on the homeostasis
      of the NK-cell compartment in children, revealing a modulatory influence of NKG2C
      copy number.

PMID- 22965786
TI  - MesoBioNano Explorer--a universal program for multiscale computer simulations of
      complex molecular structure and dynamics.
AB  - We present a multipurpose computer code MesoBioNano Explorer (MBN Explorer). The
      package allows to model molecular systems of varied level of complexity. In
      particular, MBN Explorer is suited to compute system's energy, to optimize
      molecular structure as well as to consider the molecular and random walk
      dynamics. MBN Explorer allows to use a broad variety of interatomic potentials,
      to model different molecular systems, such as atomic clusters, fullerenes,
      nanotubes, polypeptides, proteins, DNA, composite systems, nanofractals, and so
      on. A distinct feature of the program, which makes it significantly different
      from the existing codes, is its universality and applicability to the description
      of a broad range of problems involving different molecular systems. Most of the
      existing codes are developed for particular classes of molecular systems and do
      not permit multiscale approach while MBN Explorer goes beyond these drawbacks. On
      demand, MBN Explorer allows to group particles in the system into rigid
      fragments, thereby significantly reducing the number of dynamical degrees of
      freedom. Despite the universality, the computational efficiency of MBN Explorer
      is comparable (and in some cases even higher) than the computational efficiency
      of other software packages, making MBN Explorer a possible alternative to the
      available codes.

PMID- 22965787
TI  - Smoking and health-related quality of life among U.S. Adolescents.
AB  - OBJECTIVE: Smoking continues to be a public health problem among youth.
      Developmentally, adolescence is a period marked by the vulnerability to initiate
      risk behaviors such as smoking. While studies have documented associations
      between smoking and poor health related quality of life (HRQOL) among adults,
      little is known about the association among adolescents. METHODS: Data on smoking
      and HRQOL from a sample of 4,848 adolescents aged 12-17 years from the 2001-2008
      National Health and Nutrition Examination Surveys were analyzed. Smoking status
      (current, not current, and never) was determined using self-report data and serum
      cotinine levels. HRQOL was assessed based on self-reported physical and mental
      health in the last 30 days, activity limitations in the last 30 days, and general
      self-rated health. RESULTS: Compared with never smokers, adolescents who ever
      smoked reported more recent physically unhealthy days (p < .001), mentally
      unhealthy days (p < .0001), and activity limitation days (p < .01). Compared with
      never smokers, adolescents who ever smoked or who were current smokers were more
      likely to report >= 14 physically unhealthy days, >= 14 mentally unhealthy, >= 14
      activity limitation days, and fair or poor health; not current smokers were also
      more likely than never smokers to report >= 14 days for being both physically
      unhealthy and mentally unhealthy. CONCLUSIONS: Among a nationally representative
      sample of adolescents, this study found strong associations between smoking and
      HRQOL measures. The relationship of smoking to self-reported activity limitations
      warrants attention and further research. The findings underscore the importance
      of addressing smoking and subjective well-being early in the lifespan.

PMID- 22965788
TI  - Young adult smoking in peer groups: an experimental observational study.
AB  - INTRODUCTION: The aim of this experimental observational study is to examine
      whether, in a group setting (same-sex triads), passive peer influence (imitation)
      in the context of homogeneous and heterogeneous (contradictory) behavior of peer
      models affects young adults' smoking behavior. METHODS: An experiment was
      conducted among 48 daily-smoking college and university students aged 17-25.
      Participants had to complete a 30-min music task with two same-sex confederates.
      We tested the following three conditions: (a) neither of the confederates is
      smoking, (b) one confederate is smoking and the other is not, and (c) both
      confederates are smoking. The primary outcome tested was the total number of
      cigarettes smoked during the task. RESULTS: Students in the condition with two
      smoking peer models and in the condition with one smoking peer model and one
      nonsmoking peer model smoked significantly more cigarettes than those in the
      condition with two nonsmoking peer models. However, results for the condition
      with two smoking peer models did not differ significantly from the condition with
      one smoking peer model and one nonsmoking peer model. CONCLUSIONS: Our findings
      show that in a group setting, the impact of the homogeneity of smoking peers on
      young adults' smoking behavior is not greater than the impact of the
      heterogeneity of smoking and nonsmoking peers. This would suggest that the
      smoking peer in the group has a greater impact on the daily-smoking young adult,
      thus reducing or even eliminating the protective effect of the nonsmoking peer
      model.

PMID- 22965790
TI  - Micro-engineered 3D scaffolds for cell culture studies.
AB  - Cells in physiological 3D environments differ considerably in morphology and
      differentiation from those in 2D tissue culture. Naturally derived polymer
      systems are frequently used to study cells in 3D. These 3D matrices are complex
      with respect to their chemical composition, mechanical properties, and geometry.
      Therefore, there is a demand for well-defined 3D scaffolds to systematically
      investigate cell behavior in 3D. Here, fabrication techniques, materials,
      architectures, biochemical functionalizations, and mechanical properties of 3D
      scaffolds are discussed. In particular, work focusing on single cells and small
      cell assemblies grown in tailored synthetic 3D scaffolds fabricated by computer
      based techniques are reviewed and the influence of these environments on cell
      behavior is evaluated.

PMID- 22965789
TI  - Smoking status, physical health-related quality of life, and mortality in middle
      aged and older women.
AB  - INTRODUCTION: Women who smoke, particularly older women, have been relatively
      neglected in smoking research. There is a lack of knowledge concerning the
      relation of level of smoking to quality of life and mortality among middle-aged
      and older women smokers. METHODS: This study examined the relation of smoking
      status to physical health-related quality of life (PHRQL) and total mortality in
      women in the Women's Health Initiative (WHI) Observational Study. Participants
      were 90,849 postmenopausal women, who were an average age of 63.6 years at
      baseline. Analyses used multiple linear and Cox proportional hazards regression
      and controlled for age, educational level, and ethnicity. Never-smokers were the
      reference group. RESULTS: We found that smoking status was significantly related
      to PHRQL cross-sectionally at baseline and prospectively at a 3-year follow-up,
      with those who smoked having lower PHRQL. Heavier smokers showed large,
      clinically meaningful associations with PHRQL and light smokers showed small
      associations. In addition, we found that the smoking status at baseline was
      significantly related to 10-year total mortality. Both light and heavier smoking
      at baseline significantly correlated with higher mortality risk; however, the
      relationship of smoking to mortality was dose dependent. Among former smokers,
      those who had smoked longer showed significantly lower PHRQL and significantly
      increased mortality risk. CONCLUSIONS: Findings suggest that the risks of smoking
      may not be evident to light smokers and that educational interventions targeted
      to middle-aged and older women stressing the consequences of light smoking may be
      particularly beneficial.

PMID- 22965791
TI  - Poly(2-oxazoline)s and related pseudo-polypeptides.

PMID- 22965792
TI  - Neuromuscular fatigue and exercise capacity in fibromyalgia syndrome.
AB  - OBJECTIVE: To assess quadriceps strength and fatigability by using femoral nerve
      magnetic stimulation (FNMS) and their relationship to exercise capacity in
      patients with fibromyalgia syndrome (FMS) and healthy controls. METHODS: Twenty
      two women (11 with FMS, 11 controls) performed a maximal incremental cycling test
      and a quadriceps fatigue test on 2 separate visits. For quadriceps assessment, we
      used FNMS during and after maximum voluntary contraction (MVC) to evaluate
      central and peripheral factors of neuromuscular fatigue. Subjects performed sets
      of 10 intermittent (5 seconds on/5 seconds off) isometric contractions starting
      at 10% MVC, in 10% MVC increments from one set to another until exhaustion.
      Neuromuscular fatigue was assessed with FNMS after each set. RESULTS: FMS
      patients had reduced initial MVC compared to controls (mean +/- SD 102 +/- 18
      versus 120 +/- 24 Nm; P < 0.05) without significant impairment of voluntary
      activation (mean +/- SD 93.5% +/- 3.0% versus 93.1% +/- 3.4%; P = 0.74). During
      the fatigue task, FMS patients exhibited a greater fall in evoked muscular
      responses (mean +/- SD -26% +/- 6% versus -16% +/- 8% at set 50% MVC; P < 0.05),
      but not in MVC (mean +/- SD -24% +/- 7% versus -19% +/- 4% at set 50% MVC; P =
      0.12). During the cycling test, FMS patients had lowered maximal exercise
      capacity and an enhanced rate of perceived exertion (RPE) compared to controls.
      The percent reduction in evoked muscular responses during the quadriceps fatigue
      test correlated with maximum oxygen consumption (r = 0.56, P < 0.05) and RPE at
      submaximal intensity (r = 0.84, P < 0.05) during cycling. CONCLUSION: Greater
      impairment in muscle contractility is associated with enhanced perception of
      exertion and reduced maximal exercise capacity in FMS patients. Neuromuscular
      impairments should be considered as an important factor underlying functional
      limitations in FMS patients.

PMID- 22965793
TI  - Peri-procedural myocardial infarction: time for re-evaluation of its definition
      and use as an endpoint in coronary stent trials.

PMID- 22965794
TI  - Peri-procedural myocardial infarction and troponism: a quick journey through the
      land of confusion.

PMID- 22965795
TI  - Peri-operative myocardial infarction and high sensitive cardiac troponin: a start
      but by no means a finish.

PMID- 22965796
TI  - Almanac 2012--adult cardiac surgery: the national society journals present
      selected research that has driven recent advances in clinical cardiology.
AB  - This review covers the important publications in adult cardiac surgery in the
      last few years, including the current evidence base for surgical
      revascularisation and the use of off-pump surgery, bilateral internal mammary
      arteries and endoscopic vein harvesting. The changes in conventional aortic valve
      surgery are described alongside the outcomes of clinical trials and registries
      for transcatheter aortic valve implantation, and the introduction of less
      invasive and novel approaches of conventional aortic valve replacement surgery.
      Surgery for mitral valve disease is also considered, with particular reference to
      surgery for asymptomatic degenerative mitral regurgitation.

PMID- 22965797
TI  - The burden of inappropriate shocks in young people and how to avoid them.

PMID- 22965799
TI  - Overgrowth with increased proliferation of fibroblast and matrix
      metalloproteinase activity related to reduced TIMP1: a newly recognized syndrome?
AB  - We report on a child with prenatal onset of overgrowth associated with thick,
      excessive wrinkled skin and other abnormalities including cleft palate, Chiari
      malformation and polymicrogyria. His clinical features do not resemble any of the
      known reported overgrowth syndromes. Genetic evaluations, including karyotype,
      oligoarray, methylation-sensitive multiplex ligation-dependent probe
      amplification (MLPA) for 11p11.2 region, CDKN1C sequencing, GPC3 sequencing and
      dosage analysis, and HRAS sequencing, have been un-revealing.
      Immunohistochemistry done on the patient's cultured skin fibroblasts showed
      normally assembled elastic fibers and normal pattern of chondroitin sulfate
      deposition with defective deposition of Collagen I fibers. In addition, there
      were high levels of immuno-detectable metalloproteinase 3 (MMP3) and undetectable
      tissue inhibitor of metalloproteinase 1 (TIMP1). The defective collagen
      deposition in the fibroblast culture could be reversed by the broad spectrum MMP
      inhibitor, doxycycline. We also present evidence that the fibroblasts of this
      patient have an increased rate of cellular proliferation. We propose that this is
      a previously unrecognized overgrowth syndrome associated with increased cellular
      proliferation and defective collagen I deposition due to an imbalance between MMP
      and TIMP in fibroblasts.

PMID- 22965800
TI  - Twist1 as a possible biomarker for metastatic basal cell carcinoma.

PMID- 22965801
TI  - Corchorusin-D directed apoptosis of K562 cells occurs through activation of
      mitochondrial and death receptor pathways and suppression of AKT/PKB pathway.
AB  - Saponins, plant glycosides, have been reported to possess anti-cancer properties.
      Therefore the effect of corchorusin-D (COR-D), a compound isolated from Corchorus
      acutangulus, was studied in the chronic myelogenous leukemic cell line K562,
      using MTT assay, phase contrast and confocal microscopy, annexin V binding, cell
      cycle analysis and western blotting. COR-D inhibited cell growth in K562 cells
      and showed increased number of Annexin V FITC binding cells. Characteristic
      apoptotic changes, seen under phase contrast and confocal microscopes with
      accumulation of cells in the sub-G0 phase. The apoptosis involved drop in Bcl
      2/Bax ratio, loss of mitochondrial membrane potential, release of cytochrome c in
      cytosol followed by activation of caspases 9 and 3, and cleavage of PARP. Down
      regulation of pro-caspase 10 was observed along with formation of death-inducing
      signaling complex between TNF-R1 and TRADD. COR-D suppressed PDK1 and AKT with
      activation of MAP kinase family members ERK1/2, JNK1/2 and p38. Thus it induced
      apoptosis by activating mitochondrial and death receptor pathways and suppressing
      AKT/PKB rather than MAP kinase pathway. Significant enhancement of apoptosis,
      noted using specific inhibitors of ERK1/2, p38 and JNK1/2, suggests that COR-D
      can enhance apoptosis in K562 cells in combination with MAP kinase inhibitors.

PMID- 22965802
TI  - Neurotrophic factor-secreting autologous muscle stem cell therapy for the
      treatment of laryngeal denervation injury.
AB  - OBJECTIVES/HYPOTHESIS: To determine if the spontaneous reinnervation that
      characteristically ensues after recurrent laryngeal nerve (RLN) injury could be
      selectively promoted and directed to certain laryngeal muscles with the use of
      neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while
      antagonistic reinnervation is inhibited with vincristine (VNC). STUDY DESIGN:
      Basic science investigation involving primary cell cultures, gene
      cloning/transfer, and animal experiments. METHODS: MSC survival assays were used
      to test multiple individual NFs in vitro. Motoneuron outgrowth assays assessed
      the trophic effects of identified NF on cranial nerve X (CNX)-derived motoneurons
      in vitro. Therapeutic NF was cloned into a lentiviral vector, and MSCs were
      transduced to secrete NF. Sixty rats underwent left RLN transection injury, and
      at 3 weeks received injections of either MSCs (n = 24), MSCs secreting NF (n =
      24), or saline (n = 12) into the left thyroarytenoid muscle complex; half of the
      animals in the MSC groups simultaneously received left posterior cricoarytenoid
      injections of VNC, whereas half of the animals received saline. RESULTS: Ciliary
      neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in
      culture. The addition of CNTF (50 ng/mL) to CNX motoneuron cultures resulted in
      enhanced neurite outgrowth and branching. In the animal model, the injected MSCs
      fused with the denervated myofibers, immunohistochemistry demonstrated enhanced
      reinnervation based on motor endplate to nerve contact, and reverse transcriptase
      polymerase chain reaction confirmed stable CNTF expression at longest follow-up
      (4 months) in the CNTF-secreting MSC treated groups. CONCLUSIONS: MSC therapy may
      have a future role in selectively promoting and directing laryngeal reinnervation
      after RLN injury.

PMID- 22965804
TI  - Diversity and genetic population structure of fungal pathogens infecting white
      grub larvae in agricultural soils.
AB  - White grub larvae are important soil-dwelling pests in many regions of Mexico as
      they attack many important crops such as maize. The use of synthetic chemicals is
      currently the main control strategy, but they are not always effective; thus,
      other alternatives are needed. Microbial control using entomopathogenic fungi
      represents an important alternative strategy, and species within the genera
      Beauveria and Metarhizium are considered amongst the most promising candidates.
      Seventeen Beauveria spp. and two Metarhizium spp. isolates were obtained in
      surveys of white grub larvae from different regions of Guanajuato, Mexico. All
      isolates were capable of infecting healthy larvae of the white grub Phyllophaga
      polyphilla in laboratory assays, but mortality never exceeded 50 %. Isolates were
      identified using morphological and molecular methods. Based on elongation factor1
      alpha and ITS partial gene sequence data, all Beauveria isolates were identified
      as Beauveria pseudobassiana. Elongation factor1-alpha and beta-tubulin sequence
      data identified the Metarhizium isolates to be Metarhizium pingshaense. In
      contrast, three additional Metarhizium isolates obtained the previous year in the
      same region were identified as M. pingshaense, Metarhizium anisopliae and
      Metarhizium robertsii. Microsatellite genotyping showed that all B.
      pseudobassiana isolates were the same haplotype. Enterobacterial Repetitive
      Intergenic Consensus fingerprinting information confirmed no significant
      variation amongst the B. pseudobassiana isolates. The ecological role of these
      isolates and their impact on white grub larvae populations are discussed.

PMID- 22965803
TI  - Adaptation of the 3H-leucine incorporation technique to measure heterotrophic
      activity associated with biofilm on the blades of the seaweed Sargassum spp.
AB  - The ecological interaction between microorganisms and seaweeds depends on the
      production of secondary compounds that can influence microbial diversity in the
      water column and the composition of reef environments. We adapted the (3)H
      leucine incorporation technique to measure bacterial activity in biofilms
      associated with the blades of the macroalgae Sargassum spp. We evaluated (1) if
      the epiphytic bacteria on the blades were more active in detritus or in the
      biofilm, (2) substrate saturation and linearity of (3)H-leucine incorporation,
      (3) the influence of specific metabolic inhibitors during (3)H-leucine
      incorporation under the presence or absence of natural and artificial light, and
      (4) the efficiency of radiolabeled protein extraction. Scanning electron
      microscopy showed heterogeneous distribution of bacteria, diatoms, and polymeric
      extracellular secretions. Active bacteria were present in both biofilm and
      detritus on the blades. The highest (3)H-leucine incorporation was obtained when
      incubating blades not colonized by macroepibionts. Incubations done under field
      conditions reported higher (3)H-leucine incorporation than in the laboratory.
      Light quality and sampling manipulation seemed to be the main factors behind this
      difference. The use of specific metabolic inhibitors confirmed that bacteria are
      the main group incorporating (3)H-leucine but their association with primary
      production suggested a symbiotic relationship between bacteria, diatoms, and the
      seaweed.

PMID- 22965805
TI  - A selective colorimetric and ratiometric fluorescent probe for hydrogen sulfide.
AB  - A reaction-based colorimetric and ratiometric fluorescent probe based on an ICT
      strategy for selective detection of H(2)S that exploited the H(2)S-mediated
      reduction of nitrocompound to amines was explored. And it displayed high
      selectivity for H(2)S over other relevant reactive sulfur, oxygen, nitrogen
      species and other anions with more than 120 nm blue shift and the change of
      emission intensity ratio inducted by H(2)S was over 4750.

PMID- 22965806
TI  - Covarying alterations in Abeta deposition, glucose metabolism, and gray matter
      volume in cognitively normal elderly.
AB  - beta-Amyloid (Abeta), a feature of Alzheimer's disease (AD) pathology, may
      precede reduced glucose metabolism and gray matter (GM) volume and cognitive
      decline in patients with AD. Accumulation of Abeta, however, has been also
      reported in cognitively intact older people, although it remains unresolved
      whether and how Abeta deposition, glucose metabolism, and GM volume relate to one
      another in cognitively normal elderly. Fifty-two cognitively normal older adults
      underwent Pittsburgh Compound B-positron emission tomography (PIB-PET),
      [(18)F]fluorodeoxyglucose-PET, and structural magnetic resonance imaging to
      measure whole-brain amyloid deposition, glucose metabolism, and GM volume,
      respectively. Covariance patterns of these measures in association with global
      amyloid burden measured by PIB index were extracted using principal component
      analysis-based multivariate methods. Higher global amyloid burden was associated
      with relative increases of amyloid deposition and glucose metabolism and relative
      decreases of GM volume in brain regions collectively known as the default mode
      network including the posterior cingulate/precuneus, lateral parietal cortices,
      and medial frontal cortex. Relative increases of amyloid deposition and glucose
      metabolism were also noted in the lateral prefrontal cortices, and relative
      decreases of GM volume were pronounced in hippocampus. The degree of expression
      of the topographical patterns of the PIB data was further associated with visual
      memory performance when controlling for age, sex, and education. The present
      findings suggest that cognitively normal older adults with greater amyloid
      deposition are relatively hypermetabolic in frontal and parietal brain regions
      while undergoing GM volume loss in overlapping brain regions.

PMID- 22965807
TI  - Culture of primary rat hippocampal neurons: design, analysis, and optimization of
      a microfluidic device for cell seeding, coherent growth, and solute delivery.
AB  - We present the design, analysis, construction, and culture results of a
      microfluidic device for the segregation and chemical stimulation of primary rat
      hippocampal neurons. Our device is designed to achieve spatio-temporal solute
      delivery to discrete sections of neurons with mitigated mechanical stress. We
      implement a geometric guidance technique to direct axonal processes of the
      neurons into specific areas of the device to achieve solute segregation along
      routed cells. Using physicochemical modeling, we predict flows, concentration
      profiles, and mechanical stresses within pertiment sections of the device. We
      demonstrate cell viability and growth within the closed device over a period of
      11 days. Additionally, our modeling methodology may be generalized and applied to
      other device geometries.

PMID- 22965808
TI  - A contactless electrical stimulator: application to fabricate functional skeletal
      muscle tissue.
AB  - Engineered skeletal muscle tissues are ideal candidates for applications in drug
      screening systems, bio-actuators, and as implantable constructs in tissue
      engineering. Electrical field stimulation considerably improves the
      differentiation of muscle cells to muscle myofibers. Currently used electrical
      stimulators often use direct contact of electrodes with tissue constructs or
      their culture medium, which may cause hydrolysis of the culture medium, joule
      heating of the medium, contamination of the culture medium due to products of
      electrodes corrosion, and surface fouling of electrodes. Here, we used an
      interdigitated array of electrodes combined with an isolator coverslip as a
      contactless platform to electrically stimulate engineered muscle tissue, which
      eliminates the aforementioned problems. The effective stimulation of muscle
      myofibers using this device was demonstrated in terms of contractile activity and
      higher maturation as compared to muscle tissues without applying the electrical
      field. Due to the wide array of potential applications of electrical stimulation
      to two- and three-dimensional (2D and 3D) cell and tissue constructs, this device
      could be of great interest for a variety of biological applications as a tool to
      create noninvasive, safe, and highly reproducible electric fields.

PMID- 22965809
TI  - Mechanical analysis of cartilage graft reinforced with PDS plate.
AB  - OBJECTIVES/HYPOTHESIS: This study attempts to characterize the biomechanical
      properties of a PDS-cartilage composite graft for use in septorhinoplasty. STUDY
      DESIGN: Experimental Study. METHODS: This study used a PDS analog, porcine
      cartilage cut to 1 * 5 * 20 mm, and a mechanical testing platform to measure
      flexure of a composite graft. Samples were assessed in four groups based on
      variations in suture pattern and orientation. The platform measured the force
      required to deflect the sample 2 mm in single cantilever beam geometry before and
      after the polymer was affixed to the specimen. Elastic Moduli were calculated
      before and after application of the polydioxanone polymer. RESULTS: The average
      modulus of the cartilage alone was 17 +/- 0.9 MPa. The modulus of the composite
      cartilage-polymer graft with 2 suture fixation was 21.2 +/- 1.5 MPa. The 3-suture
      configuration produced an increase to 25.8 +/- 2.23 MPa. The four-suture
      configuration produced 23.1 +/- 3.19 MPa. The five-suture configuration produced
      25.7 +/- 2.6 MPa. The modulus of the analog alone was 170 +/- 30 MPa. The modulus
      of the 0.5 mm PDS was 692 +/- 37.4 MPa. The modulus of the 0.15 mm perforated PDS
      was 447 +/- 34.8 MPa. CONCLUSIONS: The study found that suturing a polymer plate
      to cartilage resulted in enhanced stiffness of the composite. Under the
      conditions of the study, there was no significant difference in elastic moduli
      between suture configurations, making the two-suture linear configuration optimal
      in the one-plane cantilever deflection model.

PMID- 22965810
TI  - Generation of a germ cell-specific mouse transgenic CHERRY reporter, Sohlh1
      mCherryFlag.
AB  - Visualization of differentiating germ cells is critical to understanding the
      formation of primordial follicles in the ovary, and the commitment of
      spermatogonial stem cells to differentiation. We engineered and generated a BAC
      transgenic mouse line, Sohlh1-mCherryFlag (S1CF), under the direction of the
      native Sohlh1 promoter. Sohlh1 is a germ cell-specific gene that encodes the
      basic helix-loop-helix (bHLH) transcriptional regulator that is essential in
      oogenesis and spermatogenesis. Sohlh1 expression is unique, and is limited to
      perinatal and early follicle oocytes and differentiating spermatogonia. The
      Sohlh1-mCherryFlag transgene was engineered to fuse SOHLH1 to the red fluorescent
      protein CHERRY with 3-tandem-FLAG tags. S1CF animals fluoresce specifically in
      the oocytes of perinatal ovaries and small follicles in adult ovaries, as well as
      in spermatogonia, a pattern that is similar to endogenous SOHLH1. Moreover, S1CF
      rescued germ cell loss and infertility in both male and female Sohlh1(-/-)
      animals. The FLAG-tag on S1CF was effective for immunostaining and
      immunoprecipitation. The Sohlh1-mCherryFlag transgenic mouse provides a unique
      model to study early germ cell differentiation, as well as in vivo imaging and
      purification of differentiating germ cells.

PMID- 22965811
TI  - microRNA-7 down-regulation mediates excessive collagen expression in localized
      scleroderma.
AB  - Localized scleroderma (LSc), a connective tissue disorder restricted to the skin
      and subcutaneous tissue, is characterized by skin fibrosis due to an excessive
      deposition of types I collagen. The mechanism of such fibrosis is still unknown,
      but epigenetics may play some roles in the excessive collagen expression. In the
      present study, we investigated the mechanism of fibrosis seen in LSc, focusing on
      microRNA (miRNA). miRNA expression was determined by PCR array, real-time PCR,
      and in situ hybridization. The function of miRNA was evaluated using specific
      inhibitor. Immunoblotting was performed to detect alpha2(I) collagen protein. PCR
      array analysis using tissue miRNA demonstrated miR-7 level was significantly
      decreased in LSc skin as well as keloid tissue compared to normal skin in vivo.
      In situ hybridization also showed miR-7 expression in dermal fibroblasts was
      decreased in LSc dermis. The transfection of specific inhibitor for miR-7 into
      cultured normal dermal fibroblasts resulted in the up-regulation of alpha2(I)
      collagen protein in vitro. Also, the serum levels of miR-7 were significantly
      decreased in LSc patients compared with healthy controls, but serum miR-29a
      levels not. Systemic or local down-regulation of miR-7 may contribute to the
      pathogenesis of LSc via the overexpression of alpha2(I) collagen, and serum miR-7
      may be useful as a disease marker. Investigation of the regulatory mechanisms of
      LSc by miRNA may lead to new treatments by the transfection into the lesional
      skin of this disease.

PMID- 22965812
TI  - Microsatellite polymorphism in the heme oxygenase-1 gene promoter and the risk of
      psoriasis in Taiwanese.
AB  - Psoriasis is a chronic disease characterized by inflammation of the skin. The
      expression of heme oxygenase-1 (HO-1), the rate-limiting enzyme involved in heme
      degradation, correlates well with the severity of psoriasis, and is a heritable
      trait. This study aimed to assess the role of (GT)(n) dinucleotide repeat
      polymorphisms in the promoter region of the HO-1 gene in Chinese-Taiwanese
      patients with psoriasis. In total, 288 patients with psoriasis and 542 control
      subjects were analyzed for the presence of the HO-1 microsatellite polymorphism
      by using polymerase chain reaction. The alleles were classified as the S and L
      alleles according to the number of (GT)(n) repeats, with the alleles with <=26
      repeats designated as S and alleles with >=27 repeats designated as L alleles.
      The subjects were then classified as having S/S, S/L, or L/L genotypes according
      to each of their HO-1 alleles. No significant difference was observed in either
      the genotype or allele distribution between the patients and healthy controls.
      However, the average number of repeats of both alleles in psoriasis patients with
      late disease onset was lower than that of psoriasis patients with early disease
      onset (26.7 +/- 3.2 vs. 27.5 +/- 3.4; P = 0.043, adjusted for age and sex), but
      the difference was not significant after additional adjustment for body mass
      index, smoking, diabetes, and hypertension (P = 0.189). Our results suggest that
      the HO-1 microsatellite polymorphism may not contribute to the genetic background
      of psoriasis in Chinese-Taiwanese patients.

PMID- 22965813
TI  - Usefulness of three-dimensional angiographic analysis of perigastric vessels
      before laparoscopic gastrectomy.
AB  - BACKGROUND: Recognition of perigastric vessel anatomy is important to safely
      perform gastric surgery, especially in the case of laparoscopic gastrectomy. This
      study was designed to reevaluate the efficacy of preoperative three-dimensional
      (3D) angiography reconstructed from enhanced multidetector-row computed
      tomography (MDCT) data and to classify right gastric artery (RGA) branching
      patterns. METHODS: Perigastric vessel anatomy was preoperatively analyzed using
      MDCT-based 3D angiography reconstructed by computer software in patients
      undergoing laparotomic (n = 75) and laparoscopic (n = 25) gastrectomy. Results
      were compared with intraoperative findings in all cases, and were also compared
      with maximum intensity projection (MIP) imaging, which is similar to conventional
      angiography, in 10 patients. RESULTS: Preoperative diagnoses by 3D angiography
      were identical to intraoperative findings. The rates of branching patterns of the
      celiac artery and left gastric vein were comparable with previous reports. The
      detection rate of the right gastric artery (RGA) was 77.0%. Branching patterns of
      the hepatic artery were classified into four types: right hepatic artery (RHA) +
      left hepatic artery (LHA) type, replaced RHA + LHA type, RHA + replaced LHA type,
      and replaced RHA + replaced LHA type. RGA ramification patterns were classified
      into three types according to hepatic arterial running patterns: distal (68.8%),
      proximal (14.3%), and caudal (16.9%). Because of vessel overlapping, RGA ramified
      points were misdiagnosed under MIP images in two of ten cases (20%). CONCLUSIONS:
      Preoperative 3D angiography is useful for a new system of classifying RGA
      ramification patterns into three types. With this system, surgeons can perform
      laparoscopic gastrectomy with lymph node dissection more safely.

PMID- 22965814
TI  - Day of surgery admission for the elective surgical in-patient: successful
      implementation of the Elective Surgery Programme.
AB  - BACKGROUND AND AIMS: The aim of this prospective cross-sectional study was to
      determine the impact of (1) ring fencing in-patient general surgical beds and (2)
      introducing a pre-operative assessment clinic (PAC) on the day of surgery
      admission (DOSA) rate in a single Irish institution. The secondary aim was to
      analyse the impact of an increased rate of DOSA on cost efficiency and patient
      satisfaction. METHODS: An 18-month period was examined following ring-fencing of
      elective and emergency surgical beds. A PAC was established during the study
      period. Prospectively collected data pertaining to all surgical admissions were
      retrieved using patient administration system software (Powerterm Pro, Eircom
      Software) and a database of performance information from Irish Public Health
      Services (HealthStat). RESULTS: Ring-fencing and PAC establishment was associated
      with a significant increase in the overall DOSA rate from 56 to 85%, surpassing
      the national target rate of DOSA (75%). Data relating specifically to general
      surgery admissions mirrored this increase in DOSA rate from a median of 5
      patients per month, before the advent of ring-fencing and PAC, to 42 patients per
      month (p < 0.0387). 100 patient surveys demonstrated high levels of satisfaction
      with DOSA, with a preference compared to admission one night pre-operatively.
      Cost analysis demonstrated overall savings of 340,370 Euro from this change in
      practice. CONCLUSION: The present study supports the practice of DOSA through the
      introduction of ring-fenced surgical beds and PAC. This has been shown to improve
      hospital resource utilisation and streamline surgical service provision in these
      economically challenging times.

PMID- 22965815
TI  - Targeting EGFR-positive cancer cells with cetuximab-ZZ-PE38: Results of in vitro
      and in vivo studies.
AB  - BACKGROUND: Arming antibody with toxins is a new approach in cancer therapy. We
      evaluated the efficacy of cetuximab-ZZ-PE38 immunocomplex in killing cancer cells
      in vitro and inhibiting tumor growth in nude mice. METHODS: Several cancer cell
      lines and human foreskin fibroblasts were tested for epidermal growth factor
      receptor (EGFR) expression and cetuximab binding using Western blot assay, enzyme
      linked immunosorbent assay (ELISA), and flow cytometry. Cell survival in vitro
      was estimated by XTT assay. Tumor size was measured twice a week. RESULTS:
      Cetuximab-ZZ-PE38 immunocomplex was significantly more effective in killing head
      and neck cancer cells than nonspecific IgG-ZZ-PE38 complex or free ZZ-PE38,
      whereas normal cells were not affected. Tumor treatment with immunocomplex
      resulted in tumor shrinkage. The immunocomplex was safe to mice at a therapeutic
      dosage of 0.25 mg/mL, whereas the dosage of 0.50 mg/mL induced liver toxicity.
      CONCLUSIONS: Cetuximab-ZZ-PE38 immunocomplex is a highly effective agent in
      killing EGFR-positive cancer cells and in tumor shrinkage.

PMID- 22965816
TI  - An analytical method for computing atomic contact areas in biomolecules.
AB  - We propose a new analytical method for detecting and computing contacts between
      atoms in biomolecules. It is based on the alpha shape theory and proceeds in
      three steps. First, we compute the weighted Delaunay triangulation of the union
      of spheres representing the molecule. In the second step, the Delaunay complex is
      filtered to derive the dual complex. Finally, contacts between spheres are
      collected. In this approach, two atoms i and j are defined to be in contact if
      their centers are connected by an edge in the dual complex. The contact areas
      between atom i and its neighbors are computed based on the caps formed by these
      neighbors on the surface of i; the total area of all these caps is partitioned
      according to their spherical Laguerre Voronoi diagram on the surface of i. This
      method is analytical and its implementation in a new program BallContact is fast
      and robust. We have used BallContact to study contacts in a database of 1551 high
      resolution protein structures. We show that with this new definition of atomic
      contacts, we generate realistic representations of the environments of atoms and
      residues within a protein. In particular, we establish the importance of nonpolar
      contact areas that complement the information represented by the accessible
      surface areas. This new method bears similarity to the tessellation methods used
      to quantify atomic volumes and contacts, with the advantage that it does not
      require the presence of explicit solvent molecules if the surface of the protein
      is to be considered. (c) 2012 Wiley Periodicals, Inc.

PMID- 22965817
TI  - Preparation of biomimetic hydrogels with controlled cell adhesive properties and
      topographical features for the study of muscle cell adhesion and proliferation.
AB  - Synthetic substrates with defined chemical and structural characteristics may
      potentially be prepared to mimic the living ECM to regulate cell adhesion and
      growth. Hydrogels with cell-adhesive peptides (0.28 +/- 0.03 nmol peptide cm(-2)
      , TTA-R-0.5; and 0.91 +/- 0.12 nmol peptide cm(-2) , TTA-R-2.0) and/or micro
      scaled topographical patterns (10, 25, and 80 um grooves) are prepared using
      enzymatic polymerization. The adherent morphology and proliferation of C2C12
      skeletal myoblasts and human aortic smooth muscle cells (hAoSM) on the hydrogels
      are studied. The newly developed hydrogels may be useful in investigating the
      roles of cell adhesion and substrate surface properties in the communication of
      adherent cells with the ECM.

PMID- 22965818
TI  - Distinctive features of classic and nonclassic (Th17 derived) human Th1 cells.
AB  - T helper17 (Th17) lymphocytes represent a third arm of the CD4(+)  T-cell
      effector responses, in addition to Th1 and Th2 cells. Th17 cells have been found
      to exhibit high plasticity because they rapidly shift into the Th1 phenotype in
      inflammatory sites. In humans, Th1 cells derived from Th17 cells express CD161,
      whereas classic Th1 cells do not; these Th17-derived Th1 cells have been termed
      nonclassic Th1 cells. In this study, we examined similarities and differences
      between classic and nonclassic human Th1 cells by assessing a panel of T-cell
      clones, as well as CD161(+)  or CD161(-)  CD4(+)  T cells derived ex vivo from
      the circulation of healthy subjects or the synovial fluid of patients with
      juvenile idiopathic arthritis. The results show that nonclassic Th1 cells can be
      identified based on CD161 expression, as well as the consistent expression of
      retinoic acid orphan receptor C, IL-17 receptor E, CCR6, and IL-4-induced gene 1,
      which are all virtually absent in classic Th1 cells. The possibility to
      distinguish these two-cell subsets by using such a panel of markers may allow the
      opportunity to better establish the respective pathogenic roles of classic and
      nonclassic (Th17 derived) Th1 cells in different chronic inflammatory disorders.

PMID- 22965819
TI  - Longitudinal association analysis of quantitative traits.
AB  - Longitudinal genetic studies provide a valuable resource for exploring key
      genetic and environmental factors that affect complex traits over time. Genetic
      analysis of longitudinal data that incorporate temporal variations is important
      for understanding genetic architecture and biological variations of common
      complex diseases. Although they are important, there is a paucity of statistical
      methods to analyze longitudinal human genetic data. In this article, longitudinal
      methods are developed for temporal association mapping to analyze population
      longitudinal data. Both parametric and nonparametric models are proposed. The
      models can be applied to multiple diallelic genetic markers such as single
      nucleotide polymorphisms and multiallelic markers such as microsatellites. By
      analytical formulae, we show that the models take both the linkage disequilibrium
      and temporal trends into account simultaneously. Variance-covariance structure is
      constructed to model the single measurement variation and multiple measurement
      correlations of an individual based on the theory of stochastic processes. Novel
      penalized spline models are used to estimate the time-dependent mean functions
      and regression coefficients. The methods were applied to analyze Framingham Heart
      Study data of Genetic Analysis Workshop (GAW) 13 and GAW 16. The temporal trends
      and genetic effects of the systolic blood pressure are successfully detected by
      the proposed approaches. Simulation studies were performed to find out that the
      nonparametric penalized linear model is the best choice in fitting real data. The
      research sheds light on the important area of longitudinal genetic analysis, and
      it provides a basis for future methodological investigations and practical
      applications. 

PMID- 22965820
TI  - Increased risk of subarachnoid hemorrhage in patients with systemic lupus
      erythematosus: a nationwide population-based study.
AB  - OBJECTIVE: A relatively common occurrence of spontaneous subarachnoid hemorrhage
      (SAH) in patients with systemic lupus erythematosus (SLE) has been noted;
      however, the subsequent studies were conflicting. This nationwide population
      based study aimed to evaluate the risk of SAH in patients with SLE. METHODS: We
      identified 16,967 SLE patients from the Taiwan National Health Insurance (NHI)
      database between 2000 and 2006, and compared the incidence rate of SAH with
      16,967 randomly selected age- and sex-matched non-SLE subjects. A Cox
      multivariable proportional hazards model was used to evaluate the risk factors of
      SAH in the SLE cohort. RESULTS: The SLE cohort had a higher risk of SAH, with an
      incidence rate ratio of 4.84 (P < 0.001). Despite a younger age, the mortality
      rate after SAH was significantly higher in the SLE cohort compared to all of the
      non-SLE SAH patients identified from the 1 million NHI beneficiaries (60.0%
      versus 38.9%; P = 0.007). Age (hazard ratio [HR] 1.03, 95% confidence interval
      [95% CI] 1.01-1.05), platelet transfusion (HR 2.75, 95% CI 1.46-5.17), red blood
      cell transfusion (HR 7.11, 95% CI 2.81-17.97), and a mean daily steroid dose >10
      mg of prednisolone or equivalent (HR 4.36, 95% CI 2.19-8.68) were independent
      risk factors for the new onset of SAH. CONCLUSION: This study demonstrated that
      SAH is a rare but associated complication of SLE with a high mortality rate.
      Other than age, higher mean daily steroid use and a history of platelet or red
      blood cell transfusion were associated with the occurrence of SAH in patients
      with SLE.

PMID- 22965821
TI  - Wisconsin Stillbirth Service Program: analysis of large for gestational age
      cases.
AB  - Since its inception in 1983, the Wisconsin Stillbirth Service Program (WiSSP) has
      reviewed over 2,600 referrals. Among 2,451 with fetal weight and gestational age
      recorded, 186 (7.6%) were large for gestational age (LGA), which is more than
      expected. We reviewed these cases to identify factors causing or contributing to
      fetal death as well as increased fetal size. LGA losses tended to occur later in
      pregnancy than non-LGA losses. The most common cause of death in LGA fetuses was
      fetal (43.5%), followed by placental (22.6%), and maternal (11.2%), which
      contrasts with previous studies involving the same database, but unselected for
      fetal weight, in which 21.5%, 40.0%, and 12.7% had fetal, placental, and maternal
      causes, respectively. The most common fetal cause was hydrops (60 cases/32.4%),
      which was most frequently idiopathic (16/26.6%), followed by cardiac (11/18.3%),
      Turner syndrome (8/13.3%), and twin-twin transfusions (6/10.0%). Placental
      causes, most commonly abruption and infarct, were more frequent in diabetic
      mothers, accounting for 33% versus only 18% in the entire LGA group. In the LGA
      group overall, 21% of mothers were diabetic, and most stillbirths in diabetic
      mothers occurred after 28 weeks. Despite large placentas (>95th centile) in 71.8%
      of the LGA cohort compared to 11% previously reported in the entire database, the
      most extreme LGA cases had a high fetoplacental ratio. We recommend pathologic
      evaluation of placentas from all stillbirths, close follow-up of pregnancies
      complicated by diabetes, and continued research into causes and pathophysiology
      of hydrops.

PMID- 22965822
TI  - Postoperative 125I brachytherapy delivered by digital model obturators for
      recurrent or locally advanced maxillary cancers.
AB  - OBJECTIVES/HYPOTHESIS: We aimed to evaluate the feasibility and effectiveness of
      postoperative (125) I brachytherapy delivered by use of digital model obturators
      for recurrent or locally advanced maxillary cancers. STUDY DESIGN: Retrospective
      study. METHODS: From 2006 to 2008, 12 patients (seven females; median age, 65
      years; range, 22-86 years) with recurrent or locally advanced maxillary cancers
      showing positive margins after surgery underwent (125) I brachytherapy by use of
      digital model obturators and interstitial implants. The radioactivity was 18.5 to
      33.3 MBq per seed, and the prescription dose was 80 to 160 Gy. Functional outcome
      of patients was evaluated by the Performance Status Scale (PSS) for head and neck
      cancer before and after brachytherapy. RESULTS: The (125) I seeds and dosages
      were well distributed in the radiation fields, and all patients had higher PSS
      scores after than before treatment with obturators. During a median follow-up of
      53 months (range, 28-62 months), local control at 3 and 5 years was 83.3% and
      66.7%, respectively, with a mean local control time of 53.5 +/- 3.79 months.
      Overall survival at 3 and 5 years was 91.7% and 71.4%, respectively, with a mean
      survival time of 56.6 +/- 2.99 months. Two patients died due to local recurrence,
      and one patient died due to lung metastasis. No patient had severe complications
      during follow-up. CONCLUSIONS: (125) I brachytherapy delivered by digital model
      obturator is effective in treating maxillary cancers with positive margins after
      maxillectomy for advanced or recurrent cancer. The method may improve the quality
      of life of patients with maxillary defects. Laryngoscope, 2012.

PMID- 22965823
TI  - Linking novelty seeking and harm avoidance personality traits to cerebellar
      volumes.
AB  - Personality traits are multidimensional traits comprising cognitive, emotional,
      and behavioral characteristics, and a wide array of cerebral structures mediate
      individual variability. Differences in personality traits covary with brain
      morphometry in specific brain regions, and neuroimaging studies showed structural
      or functional abnormalities of cerebellum in subjects with personality disorders,
      suggesting a cerebellar role in affective processing and an effect on personality
      characteristics. To test the hypothesis that cerebellar [white matter (WM) and
      cortex] volumes are correlated with scores obtained in the four temperamental
      scales of the Temperament and Character Inventory (TCI) by Cloninger, a total of
      125 healthy participants aged 18-67 years of both genders (males = 52) completed
      the TCI and underwent magnetic resonance imaging. The scores obtained in each
      temperamental scale were associated with the volumes of cerebellar WM and cortex
      of right and left hemispheres separately by using linear regression analyses. In
      line with our hypothesis, novelty seeking (NS) scores were positively associated
      with WM and cortex cerebellar volumes. Harm avoidance (HA) scores were negatively
      associated with WM and cortex cerebellar volumes. The range of individual
      differences in NS and HA scores reflects the range of variances of cerebellar
      volumes. The present data indicating a cerebellar substrate for some personality
      traits extend the relationship between personality and brain areas to a structure
      up to now thought to be involved mainly in motor and cognitive functions, much
      less in emotional processes and even less in personality individual differences.

PMID- 22965824
TI  - Microarray analysis of Dupuytren's disease cells: the profibrogenic role of the
      TGF-beta inducible p38 MAPK pathway.
AB  - BACKGROUND: Dupuytren's disease (DD) is a nodular palmar fibromatosis that causes
      irreversible permanent contracture of fingers and results in the loss of hand
      function. Surgery still remains the only available solution for DD patients but
      cannot permanently cure the disease nor reduce high recurrence rates. With this
      rationale, we designed a study aimed at an improved understanding of the
      molecular mechanisms underlying DD. Our major focus was an analysis of the global
      gene expression profile and signalling pathways in DD cells with the aim of
      identifying novel biomarkers and/or therapeutic targets. METHODS: Primary cells
      were cultured from surgically removed diseased and healthy tissue. Microarray
      expression analysis (HG-U133A array, Affymetrix) and qPCR was performed with
      total RNA isolated from primary DD cells. Mechanistic studies involving
      inhibition of p38 phosphorylation were performed on normal human fibroblasts' and
      primary DD cells' in vitro models. Expression of stem cell markers in primary
      fibroblasts/myofibroblasts was assessed as well. RESULTS: We identified 3 p38MAPK
      signalling pathway regulatory genes, THBS1, GADD45alpha and NUAK1, all involved
      in cellular proliferation and production of the extracellular matrix proteins.
      Inhibition of the p38MAPK signalling pathway induced down-regulation of
      myofibroblast markers, alpha-smooth muscle actin and palladin. A stem-cell like
      subpopulation positive for CD90 marker was identified among primary DD cells.
      CONCLUSION: The study reveals involvement of the p38 MAPK pathway as a possible
      signalling cascade in the pathogenesis of Dupuytren's disease. Moreover, a
      particular stem cell-like CD90(+) subpopulation was identified that might
      contribute to DD development.

PMID- 22965825
TI  - Navigation of a telepresence robot via covert visuospatial attention and real
      time fMRI.
AB  - Brain-computer interfaces (BCIs) allow people with severe neurological impairment
      and without ability to control their muscles to regain some control over their
      environment. The BCI user performs a mental task to regulate brain activity,
      which is measured and translated into commands controlling some external device.
      We here show that healthy participants are capable of navigating a robot by
      covertly shifting their visuospatial attention. Covert Visuospatial Attention
      (COVISA) constitutes a very intuitive brain function for spatial navigation and
      does not depend on presented stimuli or on eye movements. Our robot is equipped
      with motors and a camera that sends visual feedback to the user who can navigate
      it from a remote location. We used an ultrahigh field MRI scanner (7 Tesla) to
      obtain fMRI signals that were decoded in real time using a support vector
      machine. Four healthy subjects with virtually no training succeeded in navigating
      the robot to at least three of four target locations. Our results thus show that
      with COVISA BCI, realtime robot navigation can be achieved. Since the magnitude
      of the fMRI signal has been shown to correlate well with the magnitude of
      spectral power changes in the gamma frequency band in signals measured by
      intracranial electrodes, the COVISA concept may in future translate to
      intracranial application in severely paralyzed people.

PMID- 22965826
TI  - A novel method for reducing the effect of tonic muscle activity on the gamma band
      of the scalp EEG.
AB  - Neural oscillations in the gamma band are of increasing interest, but separating
      them from myogenic electrical activity has proved difficult. A novel algorithm
      has been developed to reduce the effect of tonic scalp and neck muscle activity
      on the gamma band of the EEG. This uses mathematical modelling to fit individual
      muscle spikes and then subtracts them from the data. The method was applied to
      the detection of motor associated gamma in two separate groups of eight subjects
      using different sampling rates. A reproducible increase in high gamma (65-85 Hz)
      magnitude occurred immediately after the motor action in the left central area (p
      = 0.02 and p = 0.0002 for the two cohorts with individually optimized algorithm
      parameters, compared to p = 0.03 and p = 0.16 before correction). Whilst the
      magnitude of this event-related gamma synchronisation was not reduced by the
      application of the EMG reduction algorithm, the baseline left central gamma
      magnitude was significantly reduced by an average of 23 % with a faster sampling
      rate (p < 0.05). In comparison, at left and right temporo-parietal locations the
      gamma amplitude was reduced by 60 and 54 % respectively (p < 0.05). The reduction
      of EMG contamination by fitting and subtraction of individual spikes shows
      promise as a method of improving the signal to noise ratio of high frequency
      neural oscillations in scalp EEG.

PMID- 22965827
TI  - Possible improvement of survival with use of zoledronic acid in patients with
      bone metastases from renal cell carcinoma.
AB  - BACKGROUND: Bisphosphonates play an indisputable role in preventing skeletal
      related events (SREs) secondary to bone metastases, and also have a direct effect
      on tumor cells. However, it remains unclear whether bisphosphonates improve
      overall survival (OS) for renal cell carcinoma (RCC) patients with bone
      metastases. METHODS: Between 1978 and 2010, a total of 45 patients who had RCC
      metastatic to bone and were classified as intermediate risk according to Memorial
      Sloan-Kettering Cancer Center criteria were included in this retrospective study.
      In this cohort, 23 patients received zoledronic acid (ZOL) treatment (ZOL-treated
      group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint
      was OS and the secondary endpoint was the SRE rate defined as the total number of
      SREs divided by the total years under study. RESULTS: For the cohort of 45
      patients, the median OS from diagnosis of bone metastases was 27.2 months.
      Multivariate analysis showed that lower serum calcium (p = 0.0083) and ZOL
      treatment (p = 0.0013) were independent factors predicting longer survival. The
      ZOL-treated group had significantly longer OS than the non-ZOL-treated group (p =
      0.0034). Patients in the ZOL-treated group experienced a lower SRE rate than
      patients in the non-ZOL-treated group (p = 0.0453). In particular, none of the
      patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in
      the non-ZOL-treated group did (p = 0.0479). CONCLUSIONS: The current study
      indicates that ZOL not only reduces SREs but possibly improves OS in these
      patients.

PMID- 22965828
TI  - Confluent and reticulated papillomatosis associated with 15q tetrasomy syndrome.

PMID- 22965829
TI  - Inter- and intramolecular reactions of 1-deoxy-1-thio-1,6-anhydrosugars with
      alpha-diazoesters: synthesis of the tagetitoxin core by photochemical ylide
      rearrangement.
AB  - The one-carbon ring expansion of 1-deoxy-1-thio-1,6-anhydrosugars, mediated by
      metal carbenes and proceeding through the intermediacy of sulfur ylides, has been
      proposed as a route for the synthesis of the tagetitoxin skeleton. Intermolecular
      reactions of such thioanhydrosugars with diazoesters afford a range of undesired
      products derived from the initially formed ylide, whereas use of an
      intramolecular process generates stable ylides which can be converted to the
      tagetitoxin skeleton by photo-Stevens rearrangement. Computational studies using
      density functional theory indicate that the photochemical rearrangement likely
      proceeds through a homolysis-recombination pathway.

PMID- 22965830
TI  - No influence of brain-derived neurotrophic factor (BDNF) polymorphisms on
      treatment response in a naturalistic sample of patients with major depression.
AB  - The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology
      of major depressive disorder (MDD) remains to be elucidated. Recent post hoc
      analyses indicated a potential association of three polymorphisms in the BDNF
      gene with worse treatment outcome in patients with the subtype of melancholic
      depression. We aimed at replicating these findings in a German naturalistic
      multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265
      (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy
      controls. We applied univariate tests and logistic regression models stratifying
      for depression subtype and gender. The three polymorphisms were not associated
      with MDD as diagnosis. Further, no associations were found in univariate tests.
      With logistic regression, we only found a tendency towards an association of the
      rs6265 (Val66Met) polymorphism with overall response to treatment (response
      rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender
      differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment
      outcome stratified for subtypes of depression did not differ significantly
      between the investigated polymorphisms or using haplotype analyses. However,
      results showed a tendency towards significance. At this stage, we cannot support
      an influence of these three polymorphisms. Further studies in larger patient
      samples to increase sample sizes of subgroups are warranted.

PMID- 22965831
TI  - Validation of the Mishel's uncertainty in illness scale-brain tumor form (MUIS
      BT).
AB  - The Mishel uncertainty in illness scale (MUIS) has been used extensively with
      other solid tumors throughout the continuum of illness. Interventions to manage
      uncertainty have been shown to improve mood and symptoms. Patients with primary
      brain tumors (PBT) face uncertainty related to diagnosis, prognosis, symptoms and
      response. Modifying the MUIS to depict uncertainty in PBT patients will help
      define this issue and allow for interventions to improve quality of life.
      Initially, 15 experts reviewed the content validity of the MUIS-brain tumor form
      (MUIS-BT). Patients diagnosed with PBT then participated in the study to test
      validity and reliability. Data was collected at one point in time. Six out of 33
      items in the original MUIS were modified to better describe PBT patients'
      uncertainty. 32 of the 186 patients in the second-stage of the study were newly
      diagnosed with PBT, 85 were on treatment, and 69 were followed-up without active
      treatment. The validity of the MUIS-BT was demonstrated by its correlations with
      mood states (P < 0.01) and symptom severity (P < 0.01) and interference (P <
      0.01). The MUIS-BT measures four constructs: ambiguity/inconsistency,
      unpredictability of disease prognosis, unpredictability of symptoms and other
      triggers, and complexity. Cronbach's alphas of the four subscales were 0.90,
      0.77, 0.75 and 0.65, respectively. The 33-item MUIS-BT demonstrated adequate
      select measures of validity and reliability in PBT patients. Based on this
      initial validation and significant correlations with symptom distress and mood
      states, further understanding of uncertainty and evaluation of measures to help
      manage patients' uncertainty can be evaluated which in turn may improve coping
      and quality of life.

PMID- 22965832
TI  - Association of common genetic variants with breast cancer risk and
      clinicopathological characteristics in a Chinese population.
AB  - Genome-wide association studies (GWAS) have identified various genetic
      susceptibility loci for breast cancer based mainly on European-ancestry
      populations. Differing linkage disequilibrium patterns exist between European and
      Asian populations, and thus GWAS-identified single nucleotide polymorphisms
      (SNPs) in one population may not be of significance in another population. In
      order to explore the role of breast cancer susceptibility variants in a Chinese
      population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast
      cancer cases and 1,534 female controls. Associations between the SNPs and
      clinicopathological features were also investigated. In addition, we evaluated
      the combined effects of associated SNPs by constructing risk models. Eight SNPs
      were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased
      breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 %
      confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor
      (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per
      allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated
      with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14
      1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to
      10q26.13/FGFR2 were associated with increased breast cancer risk via an additive
      model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22
      (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at
      rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and
      rs16886165/MAP3K1 were also associated with increased breast cancer risk, with
      per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01
      1.29), respectively. Five SNPs associated with breast cancer risk predominantly
      among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2,
      rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of
      developing breast cancer increased by 90 % for those with a combination of 6 or
      more risk alleles, compared to patients with <=3 risk alleles.

PMID- 22965833
TI  - Withaferin A causes activation of Notch2 and Notch4 in human breast cancer cells.
AB  - Ayurvedic medicine plants continue to draw attention for the discovery of novel
      anticancer agents. Withaferin A (WA) is one such small-molecule constituent of
      the ayurvedic medicine plant Withania somnifera with efficacy against cultured
      and xenografted human breast cancer cells. However, the mechanism underlying
      anticancer effect of WA is not fully understood. This study was undertaken to
      determine the role of Notch signaling in anticancer effects of WA using human
      breast cancer cells as a model. Notably, Notch signaling is often hyperactive in
      human breast cancers. Exposure of MDA-MB-231 and MCF-7 human breast cancer cells
      to pharmacological concentrations of WA resulted in cleavage (activation) of
      Notch2 as well as Notch4, which was accompanied by transcriptional activation of
      Notch as evidenced by RBP-Jk, HES-1A/B, and HEY-1 luciferase reporter assays. On
      the other hand, WA treatment caused a decrease in levels of both transmembrane
      and cleaved Notch1. The WA-mediated activation of Notch was associated with
      induction of gamma-secretase complex components presenilin1 and/or nicastrin.
      Inhibition of MDA-MB-231 and MDA-MB-468 cell migration resulting from WA exposure
      was significantly augmented by knockdown of Notch2 as well as Notch4 protein.
      Activation of Notch2 was not observed in cells treated with withanone or
      withanolide A, which are structural analogs of WA. The results of this study
      indicate that WA treatment activates Notch2 and Notch4, which impede inhibitory
      effect of WA on breast cancer cell migration.

PMID- 22965834
TI  - Audioprofiles and antioxidant enzyme genotypes in presbycusis.
AB  - OBJECTIVES/HYPOTHESIS: Audiometric patterns have been shown to indirectly provide
      information regarding the pathophysiology of presbycusis and be useful in the
      phenotyping of hereditary deafness. STUDY DESIGN AND METHODS: Hospital-based
      cohort study of adults with presbycusis, comparing the association of audiometric
      patterns and polymorphisms of antioxidant enzymes that have been linked to
      presbycusis: GSTT1, GSTM1 and NAT2. All subjects underwent a clinical evaluation
      and completed questionnaires regarding ototoxicity and noise exposure. Pure-tone
      threshold audiometry was obtained and subjects' audiograms were classified into
      specific patterns. DNA was extracted from blood and the polymorphisms of GSTT1,
      GSTM1, and the NAT2 variants (NAT2* 5A; NAT2* 6A,B) were analyzed by PCR.
      RESULTS: The audiometric patterns that were more prevalent in our cohort were
      "High-Frequency Steeply Sloping" or HFSS (33%), "High-Frequency Gently Sloping"
      or HFGS (31%), and "Flat" (27%), with other patterns being rare. We did not find
      a statistical significant effect of gender, age, hearing level, and ear side on
      the audiometric pattern. Subjects with mutant alleles for GSTT1 were more likely
      to have a HFSS audiogram than subjects with the wild type genotype. CONCLUSIONS:
      In this cohort, there was a similar prevalence for the three audiometric
      configurations HFSS, HFGS, and Flat, with other configurations being rare.
      Subjects with mutant alleles for GSTT1 were more likely to have a HFSS audiogram
      than subjects with the wild type genotype, suggesting that the basal turn of the
      cochlea is susceptible to GSTT1 regulated oxidative stress. However, further
      studies of audioprofiles with larger sample sizes may be needed to establish
      phenotype-genotype correlations in presbycusis.

PMID- 22965835
TI  - Resilient amorphous networks prepared by photo-crosslinking high-molecular-weight
      D,L-lactide and trimethylene carbonate macromers: mechanical properties and shape
      memory behavior.
AB  - Tough networks are prepared by photo-crosslinking high-molecular-weight DLLA and
      TMC macromers. These amorphous networks exhibit tunable thermal and mechanical
      properties and have excellent shape-memory features. Variation of the monomer
      ratio allows adjustment of T(g) between approximately -13 and +51  degrees C. The
      elastic moduli at room temperature can be varied between 4.5 and 2730 MPa. The
      crosslinks allow the networks to return to their original shape after
      deformation. 60:40 DLLA:TMC networks have T(g) values between room temperature
      and body temperature, with mechanical properties at body temperature close to
      soft tissues. Several medical devices are prepared from these networks.

PMID- 22965837
TI  - Structural integrity of the corpus callosum predicts long-term transfer of fluid
      intelligence-related training gains in normal aging.
AB  - Although cognitive training usually improves cognitive test performance, the
      capability to transfer these training gains into respective or functionally
      related cognitive domains varies significantly. Since most studies demonstrate
      rather limited transfer effects in older adults, aging might be an important
      factor in transfer capability differences. This study investigated the transfer
      capability of logical reasoning training gains to a measure of Fluid Intelligence
      (Gf) in relation to age, general intelligence, and brain structural integrity as
      measured by diffusion tensor imaging. In a group of 41 highly educated healthy
      elderly, 71% demonstrated successful transfer immediately after a 4-week training
      session (i.e. short-term transfer). In a subgroup of 22% of subjects transfer
      maintained over a 3-month follow-up period (i.e. long-term transfer). While short
      term transfer was not related to structural integrity, long-term transfer was
      associated with increased structural integrity in corpus and genu of the corpus
      callosum. Since callosal structural integrity was also related to age (in the
      present and foregoing studies), previously observed associations between age and
      transfer might be moderated by the structural integrity. Surprisingly, age was
      not directly associated with transfer in this study which could be explained by
      the multi-dependency of the structural integrity (modulating factors beside age,
      e.g. genetics). In this highly educated sample, general intelligence was not
      related to transfer suggesting that high intelligence is not sufficient for
      transfer in normal aging. Further studies are needed to reveal the interaction of
      transfer, age, and structural integrity and delineate mechanisms of age-dependent
      transfer capabilities.

PMID- 22965836
TI  - Dyslipidemias in the prevention of cardiovascular disease: risks and causality.
AB  - Atherosclerotic cardiovascular disease is now the major global cause of death,
      despite reductions in CVD deaths in developed societies. Dyslipidemias are a
      major contributor, but the mass occurrence of CVD relates to the combined effects
      of hyperlipidemia, hypertension, and smoking. Total blood cholesterol and LDL
      cholesterol relate to CVD risk in an independent and graded manner and fulfill
      the criteria for causality. Therapeutic reduction of these lipid fractions is
      associated with improved outcomes. There is good evidence that HDL-cholesterol,
      triglycerides, and Lp(a) relate to CVD although the evidence for a causal
      relationship is weaker. The HDL association with CVD is largely independent of
      other risk factors whereas triglycerides may be more important as signaling a
      need to look intensively for other measures of risk such as central obesity,
      hypertension, low HDL-cholesterol, and glucose intolerance. Lp(a) is an inherited
      risk marker. The benefit of lowering it is uncertain, but it may be that its
      impact on risk is attenuated if LDL-cholesterol is low.

PMID- 22965838
TI  - Human CD22 cannot fully substitute murine CD22 functions in vivo, as shown in a
      new knockin mouse model.
AB  - CD22, an inhibitory co-receptor of the B-cell receptor, shows a B-cell-specific
      expression pattern and is expressed on most B-cell lymphomas. The anti-CD22
      antibody Epratuzumab is in clinical trials for B-cell non-Hodgkin lymphoma and
      systemic lupus erythematosus, but shows a mostly unknown mode of action. We
      generated a new mouse model that expresses human CD22 instead of murine CD22
      (Huki CD22 mice), in which human CD22 can be targeted. Expression of human CD22
      on the B cells of Huki CD22 mice does not generally interfere with B-cell
      development. However, Huki CD22 mice show a reduction of the population of mature
      recirculating B cells in the bone marrow and reduced transitional and marginal
      zone B cells in the spleen, phenotypes resembling that of CD22-deficient mice.
      Similarly, enhanced BCR-induced Ca(2+)  signalling is observed in Huki CD22 mice,
      which also mount normal immune responses toward different classes of antigens.
      Huki CD22 B cells show a normal anti-hCD22 antibody-mediated endocytosis. In
      conclusion, human CD22 cannot fully substitute for murine CD22 functions,
      possibly due to the changed intracellular tail of the protein or due to lower
      expression levels. Huki CD22 mice are a valuable new model for both antibody- and
      immunotoxin-mediated targeting of human CD22.

PMID- 22965839
TI  - Regulation of protease-activated receptor-1 expression in human buccal
      fibroblasts stimulated with arecoline.
AB  - BACKGROUND: The purpose of this study was to compare the major thrombin receptor
      protease-activated receptor-1 (PAR-1) expression in normal human buccal mucosa
      and oral submucous fibrosis (OSF) specimens and further explore the potential
      mechanisms that may lead to induce PAR-1 expression. METHODS: Thirty OSF and 10
      normal buccal mucosa specimens were examined by immunohistochemistry. Buccal
      mucosal fibroblasts (BMFs) were challenged with arecoline by using Western blot
      analysis. N-acetyl-L-cysteine (NAC), LY294002, herbimycin A, NS-398, and PD98059
      were added to find the possible regulatory mechanisms. RESULTS: PAR-1 expression
      was significantly higher in OSF specimens (p < .05). Arecoline was found to
      elevate PAR-1 expression in a dose-dependent and time-dependent manner (p < .05).
      The addition of NAC, LY294002, herbimycin A, NS398, and PD98059 markedly
      inhibited the arecoline-induced PAR-1 expression (p < .05). CONCLUSION: PAR-1
      expression is significantly upregulated in areca quid chewing-associated OSF.
      Arecoline-induced PAR-1 expression was downregulated by NAC, LY294002, herbimycin
      A, NS398, and PD98059.

PMID- 22965840
TI  - Extranodal natural killer/T-cell lymphoma, nasal type: clinical and computed
      tomography findings in the head and neck region.
AB  - OBJECTIVES/HYPOTHESIS: In patients with nasal natural killer/T-cell lymphoma
      (NKTL), it is commonly without an obvious mass found in the nasal cavity by
      clinical or computed tomography (CT) findings. As a result, it takes longer to
      make a definite diagnosis when compared with other nasal malignancy. This study
      was designed to investigate clinical and CT findings of nasal NKTL. STUDY DESIGN:
      Forty-three patients with nasal NKTL were enrolled. The patients' data were
      collected retrospectively. METHODS: All patients underwent contrast-enhanced CT
      scans and endoscopic examinations. Symptoms were noted and recorded in detail.
      RESULTS: Patients with lymphoma limited to their nasal cavity or paranasal sinus
      (N/PN) presented symptoms similar to chronic rhinosinusitis, such as nasal
      obstruction and purulent nasal discharge. Patients with lymphoma of the
      nasopharynx or oropharynx (NPx/OPx) tended to present more frequently with
      epistaxis or blood-tinged sputum. On CT, NKTL was usually nonenhanced (79.1%),
      homogenous (100%), unilateral (61.9%), infiltrative (67.4%), and without central
      necrosis. Only 30.2% of the patients presented with a prominent mass. One disease
      specific sign, different from patients with chronic rhinosinusitis, was that the
      mucosa of the nasal cavity was thickened without involvement of the mucosa of the
      paranasal sinus (40.6%). CONCLUSIONS: The thickening of the mucosa of the nasal
      cavity without similar involvement of the paranasal sinuses is easily overlooked
      in patients with NKTL. In addition, the imaging findings of thickened mucosa of
      the nasal floor and/or nasal septum near the inferior meatus, a prominent mass,
      and bony destruction should raise suspicion of this diagnosis.

PMID- 22965841
TI  - Infective endocarditis caused by multidrug-resistant Streptococcus mitis in a
      combined immunocompromised patient: an autopsy case report.
AB  - An autopsy case of infective endocarditis caused by multidrug-resistant
      Streptococcus mitis was described in a patient with a combination of factors that
      compromised immune status, including autoimmune hemolytic anemia, post
      splenectomy state, prolonged steroid treatment, and IgA deficiency. The isolated
      S. mitis strain from blood culture was broadly resistant to penicillin,
      cephalosporins, carbapenem, macrolides, and fluoroquinolone. Recurrent episodes
      of bacterial infections and therapeutic use of several antibiotics may underlie
      the development of multidrug resistance for S. mitis. Because clinically isolated
      S. mitis strains from chronically immunocompromised patients have become
      resistant to a wide spectrum of antibiotics, appropriate antibiotic regimens
      should be selected when treating invasive S. mitis infections in these
      compromised patients.

PMID- 22965842
TI  - A case of NDM-1-producing Acinetobacter baumannii transferred from India to
      Japan.
AB  - A 52-year-old male Japanese businessman with massive cerebral bleeding was
      transferred from India to Japan and was admitted to our hospital. Multidrug
      resistant Acinetobacter baumannii was isolated from his sputum. The minimum
      inhibitory concentrations for this strain were as follows: imipenem, 64 MUg/ml;
      meropenem, 32 MUg/ml; ciprofloxacin, 16 MUg/ml; amikacin, 16 MUg/ml; aztreonam,
      16 MUg/ml; colistin, <1 MUg/ml. This A. baumannii strain had both bla NDM-1 and
      bla OXA-23 by polymerase chain reaction analysis. In Japan, NDM-1-producing
      bacteria are extremely rare in clinical specimens. To date, three NDM-1-positive
      cases have been detected in Japan, and this is the first case of A. baumannii
      producing NDM-1 in Japan. Our case suggests that NDM-1-producing bacteria could
      be introduced into our country easily. There is concern that various resistant
      bacteria may be transferred from epidemic countries as a result of international
      medical care.

PMID- 22965843
TI  - Bloodstream infection caused by Campylobacter lari.
AB  - We describe a case of bloodstream infection (BSI) caused by Campylobacter lari in
      a 58-year-old man diagnosed with lumbar pyogenic spondylitis. Anaerobic blood
      cultures, taken on the day of admission and on hospital day 4, were positive
      after 30 h of incubation, although no bacteria were detected by Gram staining.
      After subculture on 5 % sheep blood agar for 2 days at 35  degrees C in a 5 % CO2
      environment, capnophilic, curved, gram-negative bacteria were recovered. The
      bacteria were identified as C. lari using a combination of phenotypic
      identification methods and partial 16S rRNA gene sequencing. The BSI was
      eradicated following combination therapy with intravenous
      tazobactam/piperacillin, oral erythromycin, and sulfamethoxazole/trimethoprim.
      These results suggest that accurate identification, to the species level, is
      important to determine effective treatment of BSI caused by Campylobacter spp.
      and can help us to understand the epidemiology.

PMID- 22965844
TI  - Co-infection with invasive pulmonary aspergillosis and Pneumocystis jirovecii
      pneumonia after corticosteroid therapy.
AB  - A 95-year-old man with chronic obstructive pulmonary disease and chronic
      hepatitis C virus infection was treated for acute lung injury caused by
      Chlamydophila pneumoniae with antibiotics and high-dose corticosteroids. In
      total, 7,500 mg methylprednisolone and 680 mg prednisolone were administered over
      21 days. However, respiratory failure progressed, and chest computed tomography
      (CT) scan showed bilateral ground-glass opacity and cavity-forming consolidation
      in the right upper lobe. Despite intensive therapy, the patient died of multiple
      organ failure on day 7. CT-guided necropsy was performed, and pathological
      examination revealed invasive pulmonary aspergillosis and Pneumocystis jirovecii
      pneumonia. Invasive pulmonary aspergillosis and P. jirovecii pneumonia are both
      life-threatening opportunistic fungal infections. Co-infection of these organisms
      is rare but possible if the patient is in an extremely immunocompromised state.
      Short-term but high-dose systemic corticosteroid therapy was considered to be the
      risk factor in this case. We should pay more attention to immunocompromised hosts
      who might be suffering from co-infection of opportunistic infections. Moreover,
      we need to consider preventive measures in such high-risk cases.

PMID- 22965845
TI  - Power of IRT in GWAS: successful QTL mapping of sum score phenotypes depends on
      interplay between risk allele frequency, variance explained by the risk allele,
      and test characteristics.
AB  - As data from sequencing studies in humans accumulate, rare genetic variants
      influencing liability to disease and disorders are expected to be identified.
      Three simulation studies show that characteristics and properties of diagnostic
      instruments interact with risk allele frequency to affect the power to detect a
      quantitative trait locus (QTL) based on a test score derived from symptom counts
      or questionnaire items. Clinical tests, that is, tests that show a positively
      skewed phenotypic sum score distribution in the general population, are optimal
      to find rare risk alleles of large effect. Tests that show a negatively skewed
      sum score distribution are optimal to find rare protective alleles of large
      effect. For alleles of small effect, tests with normally distributed item
      parameters give best power for a wide range of allele frequencies. The item
      response theory framework can help understand why an existing measurement
      instrument has more power to detect risk alleles with either low or high
      frequency, or both kinds. 

PMID- 22965846
TI  - Association between arterial elasticity indices and coronary artery calcium in a
      healthy multi-ethnic cohort.
AB  - OBJECTIVES: Reduced arterial elasticity is a risk factor for coronary artery
      disease. Our main objective was to evaluate the association between large
      arterial elasticity (LAE) and small arterial elasticity (SAE) with subclinical
      atherosclerosis as reflected by the coronary artery calcium score (CACS).
      METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) includes a multi
      ethnic, population-based cohort (n = 6,814), aged 45-84 years, free from clinical
      cardiovascular disease. We undertook a post hoc analysis of the NHLBI limited
      access data set of MESA subjects (n = 6,278) to evaluate the association between
      LAE and SAE with CACS [divided in to 4 categories: none (reference), 1-99, 100
      299, and >= 300] using multivariable adjusted logistic regression analysis.
      RESULTS: After adjustments for age, sex, systolic blood pressure, anti
      hypertensive medications use, race, smoking, diabetes, high-density lipoprotein
      and total cholesterol, and high-sensitivity C-reactive protein, both LAE
      [adjusted odds ratio (aOR) 0.65; 95% CI 0.49-0.87 for CACS >= 300] and SAE (aOR
      0.68, 95% CI 0.56-0.83 for CACS >= 300) were significantly (p < 0.001 for both)
      associated with a higher CACS. CONCLUSION: Both LAE and SAE, independent of
      traditional risk factors and inflammation, are associated with subclinical
      coronary atherosclerosis.

PMID- 22965847
TI  - Congenital heart disease in Cornelia de Lange syndrome: phenotype and genotype
      analysis.
AB  - Congenital heart disease (CHD) has been reported to occur in 14-70% of
      individuals with Cornelia de Lange syndrome (CdLS, OMIM 122470) and accounts for
      significant morbidity and mortality when present. Charts from a cohort of 479
      patients with CdLS were reviewed for cardiac evaluations, gene testing and
      information to determine phenotypic severity. Two hundred fifty-nine individuals
      had either documented structural defects or minor cardiac findings. The presence
      of CHD was then quantified as a function of mutation status and severity of CdLS:
      mild, moderate, or severe. Different types of CHD were also evaluated by mutation
      status to assess for any genotype-phenotype correlation. NIPBL, SMC1A, and SMC3
      mutation-positive patients were equally likely to have CHD, although the number
      of SMC1A and SMC3 mutation-positive patients were small in comparison. Structural
      CHDs were more likely to be present in individuals with moderate and severe CdLS
      than in the mild phenotype. This study evaluates the trends of CHD seen in the
      CdLS population and correlates these findings with genotype.

PMID- 22965849
TI  - Cutaneous amyloid elastosis revealing multiple myeloma with systemic amyloidosis.

PMID- 22965850
TI  - A global analysis of xylem vessel length in woody plants.
AB  - PREMISE OF THE STUDY: Vessels are the chief conduit for long-distance water
      transport in the majority of flowering plants. Vessel length is a key trait that
      determines plant hydraulic efficiency and safety, yet relatively little is known
      about this xylem feature. * METHODS: We used previously published studies to
      generate a new global data set of vessel length in woody plants. These data were
      used to examine how evolutionary history, plant habit, environment, and growth
      ring porosity influenced vessel length. We also examined the relationship between
      mean vessel length and mean vessel diameter and maximum vessel length. * KEY
      RESULTS: Data on mean vessel length were available for stems of 130 species and
      on maximum vessel length for stems of 91 species. A phylogenetic analysis
      indicated that vessel length did not exhibit significant phylogenetic signal.
      Liana species had longer vessel lengths than in tree or shrub species. Vessel
      diameter was not predictive of mean vessel length, but maximum vessel length
      strongly predicted mean vessel length. Vessel length did not vary between species
      that differed in growth ring porosity. * CONCLUSIONS: Many traits often assumed
      to be linked to vessel length, including growth ring porosity and vessel
      diameter, are not associated with vessel length when compared interspecifically.
      Sampling for vessel length has been nonrandom, e.g., there are virtually no data
      available for roots, and sampling for environment has been confounded with
      sampling for habit. Increased knowledge of vessel length is key to understanding
      the structure and function of the plant hydraulic pathway.

PMID- 22965848
TI  - Raloxifene inhibits growth of RT4 urothelial carcinoma cells via estrogen
      receptor-dependent induction of apoptosis and inhibition of proliferation.
AB  - Bladder cancer is the fifth most common type of cancer in the USA, with over
      70,000 new cases diagnosed each year. Treatment often involves invasive surgical
      therapies, as chemotherapy alone is often ineffective and associated with high
      recurrence rates. Identification of estrogen receptor-beta (ERbeta) in up to 75 %
      of urinary tumors raises the question of whether this receptor could be targeted
      to effectively treat bladder cancer. In this study, a panel of five bladder
      cancer cell lines representing a variety of disease stage and grades were treated
      with the antiestrogens 4-hydroxytamoxifen, raloxifene, or the pure antagonist ICI
      182,780. All cell lines were ERbeta positive while only a few expressed estrogen
      receptor-alpha (ERalpha). Notably, all but the TCCSUP cell line were growth
      inhibited 20-100 % by at least two antiestrogens. Using RT4 cells, we demonstrate
      that growth inhibition by raloxifene is ER dependent and either ERalpha or ERbeta
      can mediate this response. Activation of caspase-3 and its effector poly-ADP
      ribose polymerase (PARP) demonstrate that raloxifene-induced growth inhibition is
      in part the result of increased apoptosis; this PARP cleavage was ER dependent.
      Moreover, changes in the expression of cell cycle genes indicate that cell
      proliferation is also affected. Specifically, raloxifene treatment results in the
      stabilization of p27 protein, likely via the downregulation of S-phase kinase
      associated protein (SKP2). Expression of the negative cell cycle regulator B-cell
      translocation gene (BTG2) is also increased, while cyclin D1 transcription is
      reduced. These results indicate that antiestrogens may be useful therapeutics in
      the treatment of bladder cancer by targeting ER and inhibiting growth via
      multiple mechanisms.

PMID- 22965851
TI  - Reconstructing the origin and elaboration of insect-trapping inflorescences in
      the Araceae.
AB  - PREMISE OF THE STUDY: Floral traps are among the most sophisticated devices that
      have evolved in angiosperms in the context of pollination, but the evolution of
      trap pollination has not yet been studied in a phylogenetic context. We aim to
      determine the evolutionary history of morphological traits that facilitate trap
      pollination and to elucidate the impact of pollinators on the evolution of
      inflorescence traps in the family Araceae. * METHODS: Inflorescence morphology
      was investigated to determine the presence of trapping devices and to classify
      functional types of traps. We inferred phylogenetic relationships in the family
      using maximum likelihood and Bayesian methods. Character evolution of trapping
      devices, trap types, and pollinator types was then assessed with maximum
      parsimony and Bayesian methods. We also tested for an association of trap
      pollination with specific pollinator types. * KEY RESULTS: Inflorescence traps
      have evolved independently at least 10 times within the Araceae. Trapping devices
      were found in 27 genera. On the basis of different combinations of trapping
      devices, six functional types of traps were identified. Trap pollination in
      Araceae is correlated with pollination by flies. * CONCLUSIONS: Trap pollination
      in the Araceae is more common than was previously thought. Preadaptations such as
      papillate cells or elongated sterile flowers facilitated the evolution of
      inflorescence traps. In some clades, imperfect traps served as a precursor for
      the evolution of more elaborate traps. Traps that evolved in association with fly
      pollination were most probably derived from mutualistic ancestors, offering a
      brood-site to their pollinators.

PMID- 22965853
TI  - Morphine exposure during HIV encephalitis in SCID mice.
AB  - HIV encephalitis (HIVE) is often complicated by opiate abuse. Based on human
      pathological, animal and in vitro studies, opiates are thought to exacerbate
      HIVE. To test this hypothesis we exposed 10 week old SCID mice with HIVE to
      morphine and examined histopathological parameters. Mice inoculated
      intracerebrally with either HIV-infected or uninfected (control mice) human
      macrophages were immediately implanted subcutaneously with pellets containing
      saline, morphine or morphine plus naltrexone. They were sacrificed after 10 days.
      Immunostaining for astrocytes (GFAP), mouse mononuclear phagocytes (CD45) and
      neuronal dendrites (MAP2) was analyzed by densitometry. HIVE mice exposed to
      either saline, morphine or morphine plus naltrexone also had brain sections
      counted for HIV+ human macrophages. Typical HIVE pathology was present,
      consistent with previously published studies. Surprisingly, there were no effects
      on astrogliosis, microgliosis and MAP2 decreases in the HIVE, morphine treated
      group. There was also no effect of morphine exposure on numbers of p24+ human
      macrophages. These results emphasize the complexities of modeling opiate effects
      in HIVE and the potential significance of opiate abuse on HIVE in humans.

PMID- 22965852
TI  - Chronic treatment with anti-bipolar drugs causes intracellular alkalinization in
      astrocytes, altering their functions.
AB  - Bipolar disorder I and II are affective disorders with mood changes between
      depressive and manic (bipolar I) or hypomanic (bipolar II) periods. Current
      therapy of these conditions is chronic treatment with one or more of the anti
      bipolar drugs, Li(+) ('lithium'), carbamazepine and valproic acid. The
      pathophysiology of bipolar disorder is multifactorial and far from clear. Recent
      data on the dependence of normal brain function on neuronal-astrocytic
      interactions raise the possibility of astrocytic involvement. We will discuss our
      previously published and new results on effects of chronic treatment of primary
      cultures of normal mouse astrocytes with any of three conventional anti-bipolar
      drugs. The focus will be on several drug-induced events in relation to
      therapeutic effects of the drugs, such as myo-inositol uptake, intracellular pH
      and alkalinization, drug-induced modulation of glutamatergic activity in
      astrocytes and release of astrocytic 'gliotransmitters'. Finally, we will discuss
      the importance of phospholipase A2 (PLA(2)) and arachidonic acid cascade in drug
      treated astrocytes, partly based on Dr. Barneda Cuirana's published thesis. All
      three drugs cause gradual intracellular alkalinization through different
      mechanisms. Alkalinization inhibit myo-inositol uptake, resulting in reduced
      inositolphosphate/phospholipid signaling. Accordingly, transmitter-induced
      increase in free intracellular Ca(2+) ([Ca(2+)](i)) becomes inhibited, aborting
      release of astrocytic 'gliotransmitters'. The reduction of "gliotransmitter"
      effects on neurons may have therapeutic effects in mania. Alkalinization also up
      regulates expression of cPLA(2), an enzyme releasing arachidonic acid, and
      triggered arachidonic acid cascade and production, but perhaps not release, of
      prostaglandins. Whenever tested, identical effects were observed in freshly
      isolated astrocytes, but not neurons, from carbamazepine-treated healthy animals.

PMID- 22965854
TI  - Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice.
AB  - BACKGROUND: Whether systemic inflammation compromises the pulmonary system is
      largely unknown. We tested the hypothesis that chronic low-grade systemic
      inflammation damages alveolar wall cells. METHODS: A chronic low-grade systemic
      inflammatory state was induced in 8-week-old male C57/BL6J mice by administration
      of lipopolysaccharide (LPS, 44.4 MUg/day) for a 90-day period by subcutaneous
      implantation of a delayed-release pellet system. Acute systemic inflammation was
      induced in another group of mice by a single intraperitoneal injection of LPS
      (125 MUg/body). The lungs of mice were examined for histologic changes and
      genetic damage to alveolar wall cells. RESULTS: Chronic LPS exposure for a 30-day
      period or a 90-day period did not cause any obvious architectural changes in the
      lungs except for a mild level of alveolar macrophage infiltration. Despite the
      lack of architectural changes in the lung, immunofluorescence staining for
      gammaH2AX and phosphorylated 53BP1 showed that chronic LPS exposure resulted in
      an almost doubling of the number of DNA double-strand breaks (DSBs) in type 1 and
      type 2 alveolar epithelial cells and in alveolar endothelial cells. Acute LPS
      exposure also resulted in a doubling of the number of DSBs in type 1 and type 2
      alveolar epithelial cells and in alveolar endothelial cells at 24 h, but the
      increased number of DSBs returned to the baseline level by 48 h. CONCLUSIONS:
      These results suggest that chronic systemic low-grade inflammation induces
      persistent DNA damage in alveolar epithelial and endothelial cells before
      architectural changes in the lung become evident.

PMID- 22965855
TI  - Prediction of phenotypes of missense mutations in human proteins from biological
      assemblies.
AB  - Single nucleotide polymorphisms (SNPs) are the most frequent variation in the
      human genome. Nonsynonymous SNPs that lead to missense mutations can be neutral
      or deleterious, and several computational methods have been presented that
      predict the phenotype of human missense mutations. These methods use sequence
      based and structure-based features in various combinations, relying on different
      statistical distributions of these features for deleterious and neutral
      mutations. One structure-based feature that has not been studied significantly is
      the accessible surface area within biologically relevant oligomeric assemblies.
      These assemblies are different from the crystallographic asymmetric unit for more
      than half of X-ray crystal structures. We find that mutations in the core of
      proteins or in the interfaces in biological assemblies are significantly more
      likely to be disease-associated than those on the surface of the biological
      assemblies. For structures with more than one protein in the biological assembly
      (whether the same sequence or different), we find the accessible surface area
      from biological assemblies provides a statistically significant improvement in
      prediction over the accessible surface area of monomers from protein crystal
      structures (P = 6e-5). When adding this information to sequence-based features
      such as the difference between wildtype and mutant position-specific profile
      scores, the improvement from biological assemblies is statistically significant
      but much smaller (P = 0.018). Combining this information with sequence-based
      features in a support vector machine leads to 82% accuracy on a balanced dataset
      of 50% disease-associated mutations from SwissVar and 50% neutral mutations from
      human/primate sequence differences in orthologous proteins.

PMID- 22965856
TI  - Full-time workers with precarious employment face lower protection for receiving
      annual health check-ups.
AB  - BACKGROUND: Precarious employment is one of the social determinants of health. In
      2010, 34.4% of Japanese workers fell into this employment category. The purpose
      of our study was to assess whether the use of annual health check-ups varied by
      worker contract type. METHODS: Using 2007 nationally representative survey data,
      we compared the annual health check-up compliance of permanently employed full
      time workers versus that of precariously employed workers (hourly, dispatched,
      and fixed-term workers). RESULTS: Dispatched workers and hourly workers received
      health check-ups less often compared with permanent workers. Hourly young male
      workers received health check-ups five times less frequently than permanent
      workers. The percentage of workers who consulted a physician after receiving
      advice to do so did not differ by employment types, except in older men.
      CONCLUSIONS: In Japan, workers with precarious employment, most notably hourly
      and dispatched workers, had a lower rate of health check-ups compared with full
      time workers in permanent positions.

PMID- 22965857
TI  - Primary surgical treatment of T3 glottic carcinoma: long-term results and
      decision-making aspects.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the efficacy of
      primary surgical treatment in the management of T3 glottic carcinomas. STUDY
      DESIGN: Retrospective clinical study. METHODS: A retrospective evaluation of the
      records for all patients treated with primary surgery for T3 glottic carcinomas
      at a tertiary referral center between 1980 and 2005 was carried out. Data for the
      5-year disease-specific survival (DSS) were assessed, as well as local control
      rates in relation to vocal cord immobility, N classification, choice of surgical
      modality, and adjuvant therapy. Patients who underwent partial laryngectomy were
      also evaluated in relation to organ preservation and the rate of permanent
      tracheotomies. RESULTS: The 5-year DSS in the 120 patients was 78.3%. Positive
      neck disease was shown to be a significant negative prognostic factor. Organ
      preservation was achieved in 90.1% of the patients who underwent partial
      laryngectomy and in 50% of the overall patient group. The occult metastasis rate
      was 14%. CONCLUSIONS: Primary surgical treatment is an effective modality against
      T3 glottic carcinomas. Partial laryngectomy is a reliable method in carefully
      selected cases. Low complication rates can be expected.

PMID- 22965858
TI  - CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel
      disease.
AB  - Purinergic signaling and associated ectonucleotidases, such as CD39 and CD73,
      have been implicated in the pathogenesis of inflammatory bowel disease (IBD).
      CD39 is known to be a Treg memory cell marker, and here we determine the
      phenotype and function of CD73(+) CD4(+)  T lymphocytes in patients with IBD. We
      describe elevated levels of CD73(+) CD4(+)  T cells in the peripheral blood and
      intestinal lamina propria of patients with active IBD. The functional phenotype
      of these CD73(+) CD4(+)  T cells was further determined by gene expression, ecto
      enzymatic activity, and suppressive assays. Increased numbers of CD73(+) CD4(+) 
      T cells in the periphery and lamina propria were noted during active
      inflammation, which returned to baseline levels following anti-TNF treatment.
      Peripheral CD73(+) CD4(+)  T cells predominantly expressed CD45RO, and were
      enriched with IL-17A(+)  cells. The CD73(+) CD4(+)  cell population expressed
      higher levels of RORC, IL-17A, and TNF, and lower levels of FOXP3 and/or CD25,
      than CD73(-) CD4(+)  T cells. Expression of CD73 by peripheral CD4(+)  T cells
      was increased by TNF, and decreased by an anti-TNF monoclonal antibody
      (infliximab). In vitro, these peripheral CD73(+) CD4(+)  T cells did not suppress
      proliferation of CD25(-)  effector cells, and expressed higher levels of pro
      inflammatory markers. We conclude that the CD73(+) CD4(+)  T-cell population in
      patients with active IBD are enriched with cells with a T-helper type 17
      phenotype, and could be used to monitor disease activity during treatment.

PMID- 22965859
TI  - How reliable are left ventricular ejection fraction cut offs assessed by
      echocardiography for clinical decision making in patients with heart failure?
AB  - We aimed to study the potential influence of the variability in the assessment of
      echocardiographically measured left ventricular ejection fraction (LVEF) on
      indications for the implantation of internal cardioverter defibrillator and/or
      cardiac resynchronization devices in heart failure patients. TIME-CHF was a
      multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged
      >=60 years. Patients had their LVEF assessed at the recruiting centre using
      visual assessment, the area-length or biplane Simpson's method. Echocardiographic
      data were transferred to the study core-lab for re-assessment. Re-assessment in
      the core-lab was done with biplane Simpson's method, and included an appraisal of
      image quality. 413 patients had the LVEF analyzed at the recruiting centre and at
      the core lab. Image quality was optimal in 191 and suboptimal in 222. Overall,
      the correlation between LVEF at the recruiting centres and at the core-lab was
      good, independent of image quality (R2 = 0.62). However, when a LVEF <=30 % or
      >=30 % was used as a cut-off, about 20 % of all patients would have been re
      assigned to having either a LVEF above or below the cut-off, this proportion was
      not significantly influenced by image quality. We conclude that correlation
      between LVEF assessed by different centres based on the same ultrasound data is
      good, regardless of image quality. However, one fifth of patients would have been
      re-assigned to a different category when using the clinically important cut-off
      of 30 %.

PMID- 22965860
TI  - Treating hearing loss in patients with infantile Bartter syndrome.
AB  - OBJECTIVES/HYPOTHESIS: Most existing studies about infantile Bartter syndrome
      (BS) have focused on renal function, and deafness has not been closely studied.
      Our objective was to evaluate the treatment of hearing impairment in children
      with infantile BS and analyze relevant, unexplored issues. STUDY DESIGN:
      Retrospective chart review. METHODS: The present study was conducted in a
      tertiary referral center over a 20-year period involving children with infantile
      BS. Demographic factors, general health status, genetic information, features of
      hearing loss, and the outcome of cochlear implantation as determined mainly by
      the categories of auditory performance (CAP), as well as imaging of the temporal
      bones, were evaluated. RESULTS: Six children with infantile BS were identified,
      four girls and two boys. One child had terminal renal insufficiency and one had
      undergone kidney transplantation; all children had several hospital admissions
      due to renal dysfunction. Sensorineural hearing loss was congenital, bilateral,
      and profound in all children. Five patients were treated with cochlear implants
      resulting in improved speech perception and development without any exceptional
      performance (CAP scores, 4-6), mainly because of the delayed treatment and the
      comorbidities. Anatomic ear anomalies were not observed in any case. CONCLUSIONS:
      Hearing loss in children with infantile BS is congenital and profound but not
      related to inner ear malformations. Although cochlear implantation results in
      certain benefits, general health status and delayed referral to cochlear implant
      centers have a negative impact on speech perception and development.

PMID- 22965861
TI  - Development of protein-cage-based delivery nanoplatforms by polyvalently
      displaying beta-cyclodextrins on the surface of ferritins through copper(I)
      catalyzed azide/alkyne cycloaddition.
AB  - Protein cages are spherical hollow macromolecules that are attractive platforms
      for the construction of nanoscale cargo delivery vehicles. Human heavy-chain
      ferritin (HHFn) is modified genetically to control the number and position of
      functional groups per cage. 24 beta-CDs are conjugated precisely to the modified
      HHFn in specific locations through thiol-maleimide Michael-type addition followed
      by copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC). The resulting human
      ferritins displaying beta-CDs (beta-CD-C90 HHFn) can form inclusion complexes
      with FITC-AD, which can slowly release the guest molecule reversibly in a buffer
      solution via non-covalent beta-CD/AD interactions. beta-CD-C90 HHFn can
      potentially be used as delivery vehicles for insoluble drugs.

PMID- 22965862
TI  - Familial 25.3 Mb inverted duplication of bands q32.1 to q35.1 on chromosome 4
      with psychomotor impairments.

PMID- 22965863
TI  - Family accommodation in pediatric anxiety disorders.
AB  - BACKGROUND: Family accommodation has been studied in obsessive compulsive
      disorder using the Family Accommodation Scale (FAS) and predicts greater symptom
      severity, more impairment, and poorer treatment outcomes. However, family
      accommodation has yet to be systematically studied among families of children
      with other anxiety disorders. We developed the Family Accommodation Scale-Anxiety
      (FASA) that includes modified questions from the FAS to study accommodation
      across childhood anxiety disorders. The objectives of this study were to report
      on the first study of family accommodation across childhood anxiety disorders and
      to test the utility of the FASA for assessing the phenomenon. METHODS:
      Participants were parents (n = 75) of anxious children from two anxiety disorder
      specialty clinics (n = 50) and a general outpatient clinic (n = 25). Measures
      included FASA, structured diagnostic interviews, and measures of anxiety and
      depression. RESULTS: Accommodation was highly prevalent across all anxiety
      disorders and particularly associated with separation anxiety. Most parents
      reported participation in symptoms and modification of family routines as well as
      distress resulting from accommodation and undesirable consequences of not
      accommodating. The FASA displayed good internal consistency and convergent and
      divergent validity. Accommodation correlated significantly with anxious but not
      depressive symptoms, when controlling for the association between anxiety and
      depression. Factor analysis of the FASA pointed to a two-factor solution; one
      relating to modifications, the other to participation in symptoms. CONCLUSIONS:
      Accommodation is common across childhood anxiety disorders and associated with
      severity of anxiety symptoms. The FASA shows promise as a means of assessing
      family accommodation in childhood anxiety disorders.

PMID- 22965864
TI  - Endoscopic trans(naso)orbital management of supraorbital mucoceles with biliary T
      tube stenting.
AB  - The objective of this article is to describe our surgical technique for accessing
      orbital and supraorbital ethmoid sinus mucoceles and the novel application of a
      biliary T-tube to stent and redirect mucociliary flow into the frontal recess. We
      describe in technical terms our surgical approach and the use of an 8-Fr
      pediatric biliary T-tube as a paranasal sinus stent with demonstrative case
      reports. Four patients have been successfully managed employing the endoscopic
      trans(naso)orbital approach to access and marsupialize supraorbital and
      superiorly located orbital mucoceles without egress to the frontal recess.
      Patency of drainage was maintained by utilizing a flexible, pediatric, biliary T
      tube that is inserted via an above (trephination) and below (endoscopic) approach
      in three patients, and without the need for stenting in one patient (median
      follow-up, 14.5 months). The presented surgical strategy is safe and effective in
      accessing and maintaining long-term patency of problematic supraorbital and
      superiorly located intraorbital mucoceles without communication to the frontal
      recess.

PMID- 22965865
TI  - Occupational physicians' perceptions and impact of 2009 GMC consent guidelines.
AB  - BACKGROUND: In 2009, the General Medical Council (GMC) updated its guidance on
      consent, introducing a new statement that employees should be offered the
      opportunity to view reports, before the reports are sent to the employer. AIMS:
      To investigate the effects of this change on the perceptions and practice of
      occupational physicians. METHODS: A cross-sectional survey of UK occupational
      physicians via the Society of Occupational Medicine e-newsletter, seeking their
      opinions of the anticipated and actual effects of the guidance on employers,
      employees, occupational physicians and occupational health services. RESULTS: Two
      hundred and ninety-five completed questionnaires were returned (estimated
      response rate 30%). Respondents included 25% of accredited UK specialists. Some
      reported improved standards and greater transparency, however the change was
      generally perceived as unfavourable, with employee and employer losses: 50%
      reported delay providing timely advice to employers and 35% reported delays in
      employees returning to work. Significant variation in practice and increased
      costs were reported, with variable effects on different services. Difficulties in
      areas such as pensions and health surveillance were reported. Some occupational
      physicians had moved to instant reporting; others had moved away from this to
      allow more care with wording of reports. CONCLUSIONS: We found significant
      variations in practice between occupational physicians and concerns of employee
      and employer losses as a result of changes to the GMC consent guidance. Clearer
      guidance on practical implementation was desired. The background ethical
      reasoning should be stated so that the parameters of the guidance are delineated
      and its reach should be clarified.

PMID- 22965866
TI  - Occupational and individual risk factors for dysphonia in teachers.
AB  - BACKGROUND: In recent decades several groups of researchers have been interested
      in describing and understanding vocal morbidity in teachers in order to explain
      the large number of teachers diagnosed with dysphonia and account for the
      absenteeism attributed to vocal disability. AIMS: To determine the proportion of
      teachers who reported a diagnosis of dysphonia and measure associations between
      individual and contextual factors and the event of interest. METHODS: Teachers
      were recruited from the city of Belo Horizonte and invited to complete a web
      based institutional intranet questionnaire. RESULTS: In total, 649 teachers
      responded; 32% (CI 28.5-35.5) reported that they had received a physician
      diagnosis of dysphonia. This prevalence was significantly higher among female
      teachers (prevalence ratio (PR) 2.33; CI 1.41-3.85), and groups who reported
      limited technical resources and equipment (PR 1.56; CI 1.14-2.15), a diagnosis of
      gastritis (PR 1.59; CI 1.28-1.98), not being summoned for an annual physician
      examination (PR 0.47; CI 0.32-0.68), or absenteeism (PR 1.39; CI 1.06-1.81).
      CONCLUSIONS: The high prevalence of dysphonia in teachers was not associated with
      any individual variables, except for sex and comorbidity (diagnosis of
      gastritis). Limited technical resources and equipment were associated with
      dysphonia and suggests policy change is important in preventing dysphonia.

PMID- 22965867
TI  - Clinical stress assessment using a visual analogue scale.
AB  - BACKGROUND: Clinicians increasingly require short, efficient methods for
      assessing distress, both in applied research and clinical settings. Most of the
      available questionnaires are unsuitable for busy clinical settings. The visual
      analogue scale (VAS) is widely but empirically used to assess perceived stress.
      AIMS: To provide evidence on two of the psychometric properties of the VAS: its
      discriminative sensitivity (capacity to highlight a difference between groups)
      and its interconcept validity (the relationship between VAS stress assessment and
      the assessment of different, but similar concepts). METHODS: Employees attending
      occupational health centres were randomly selected and completed the VAS and also
      either the Perceived Stress Scale (PSS) or the Hospital Anxiety and Depression
      Scale (HADS). Analyses of variance were performed to study group effects (age,
      sex, marital status, parental status, occupational status) on stress scores (PSS
      and VAS). RESULTS: In total, 763 employees participated of whom 501 completed the
      PSS and 262 the HADS. P-values obtained for the effects of sex, age and
      occupational status were lower with the VAS than with the PSS. Correlations
      between the VAS and the anxiety subscale, depression subscale and total score of
      the HADS were 0.66, 0.45 and 0.65, respectively. Other tools used to assess
      aspects of psychological distress are known to have similar correlations.
      CONCLUSIONS: Our findings provide evidence that the VAS is at least as
      discriminating as a questionnaire when it comes to highlighting differences in
      stress levels between two groups, and the observed correlations with related
      constructs support its construct validity.

PMID- 22965868
TI  - Urrets-Zavalia syndrome following penetrating keratoplasty for keratoconus.
AB  - BACKGROUND: Urrets-Zavalia syndrome (UZS) consists of a fixed dilated pupil
      associated with iris atrophy. It is a poorly understood complication following
      penetrating keratoplasty (PKP) for keratoconus (KC). In this work, we aim to
      establish the incidence, visual outcomes, and an understanding of UZS. METHODS:
      This was a retrospective single-center study in a tertiary eye service in the
      United Kingdom of consecutive patients with UZS following PKP for KC in a 10-year
      period. Post-operative complications, including raised intraocular pressure
      (IOP), were recorded. UZS patients and age-matched control patients who had
      undergone PKP for KC without developing UZS attended a comprehensive clinical
      assessment. Anterior segment indocyanine green (ICG) angiography assessed iris
      perfusion. RESULTS: The incidence of UZS was 16.2 %. There was no difference in
      LogMAR VA or Pelli-Robson contrast sensitivity between groups. There was higher
      first-day post-operative IOP in UZS (p = 0.02). UZS patients had increased pupil
      size (p = 0.09) with reduced response to pilocarpine 2 % (p < 0.001). ICG
      angiography revealed delayed/reduced iris vasculature filling in UZS compared
      with normal filling patterns of controls. CONCLUSIONS: Elevated post-operative
      IOP within 24 h was a significant factor in the development of UZS. Visual
      function in UZS patients was unaffected. UZS patients developed longstanding
      mydriasis with reduced reactivity to topical pilocarpine 2 %. ICG angiography
      confirmed iris vessel ischemia; supporting the theory that iris ischemia
      resulting from occlusion of iris root vessels due to elevated IOP causes UZS. We
      advocate rigorous intraoperative management of ocular viscoelastic devices and
      aggressive postoperative IOP control in patients undergoing PKP for KC.

PMID- 22965869
TI  - Global health initiatives of US otolaryngology residency programs: 2011 global
      health initiatives survey results.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this work were to quantify the
      involvement of US otolaryngology residency programs in global health endeavors,
      identify goals and services provided, and determine the participation of
      residents and fellows. STUDY DESIGN: Cross-sectional survey of US otolaryngology
      faculty. METHODS: A 10-point online questionnaire was distributed to 103 US
      otolaryngology residency program directors; all faculty involved in global health
      volunteerism were invited to participate. RESULTS: Twenty-nine global health
      initiatives were represented. Most of the 24 residency programs involved (66%)
      had organized global health offices at their institutions; only 4% actually
      cooperated with these offices. Most often, only one attending (55%) was involved
      at each institution. Residents/fellows participated 65% of the time. Abroad, US
      otolaryngologists worked with freestanding hospitals or clinics (24%), American
      nongovernmental organizations (17%), academic centers (14%), and remote locations
      (14%). Most (96%) provided specialty surgical services, but some provided primary
      care (28%) and general surgical services (14%); 72% trained foreign surgeons.
      Most respondents (79%) reported that the clinical work done abroad was
      substantial enough for Accreditation Council for Graduate Medical Education
      (ACGME) standards. Only one fifth of respondents knew the name of the nearest
      otolaryngology training institution. Humanitarian aid was the most prevalent goal
      (100%), followed by resident/fellow exchange (45%) and faculty exchange (21%).
      CONCLUSIONS: At least a quarter of US otolaryngology residency programs engage in
      global health volunteerism. Most do not utilize institutional global health
      resources and are unaware of otolaryngology training programs abroad. There may
      be a role for global health education within the ACGME competency of systems
      based practice.

PMID- 22965870
TI  - Crystal structure of NirD, the small subunit of the nitrite reductase NirbD from
      Mycobacterium tuberculosis at 2.0 A resolution.
AB  - NirD is part of the nitrite reductase complex NirBD that catalyses the reduction
      of nitrite to NH(3) in nitrate assimilation and anaerobic respiration. The
      crystal structure analysis of NirD from Mycobacterium tuberculosis shows a double
      beta-sandwich fold. NirD is related in three-dimensional structure and sequence
      to the Rieske proteins; however, it does not contain any Fe-S cluster or other
      cofactors that might be involved in electron transfer. A cysteine residue at the
      protein surface, conserved in NirD homologues lacking the iron-sulfur cluster
      might be important for the interaction with NirB and possibly stabilize one of
      the Fe-S centers in this subunit.

PMID- 22965871
TI  - Large trigeminal schwannoma of the infratemporal fossa: evaluation of
      neoangiogenesis in this rare neoplasm.
AB  - BACKGROUND: Trigeminal schwannomas are uncommon intracranial tumors. Extracranial
      trigeminal schwannomas in the infratemporal fossa are rare. METHODS: We present a
      case with a clinical history of facial pain. MRI and CT scans showed a mass
      arising from the infratemporal fossa extending into the intracranial space.
      RESULTS: We performed a combined neurosurgical and maxillofacial approach with
      preoperative endovascular embolization. Complete removal of the parasellar
      component was achieved with a minimal extracranial neoplastic residual. High
      microvessel density, reflecting intense neoangiogenesis, was detected through the
      immunohistochemical staining with endoglin. CONCLUSIONS: Due to the unique
      development pattern of trigeminal schwannoma involving multiple intracranial
      fossae and extracranial compartment, we chose a combined neurosurgical and
      maxillofacial approach with preoperative embolization of the tumor.
      Immunohistochemical findings suggest that the extensive growth observed may be
      related to an intense neoangiogenesis, opening the perspective to novel
      therapeutic options based on the inhibition of neoangiogenesis.

PMID- 22965872
TI  - Co-occurring mental health problems and peer functioning among youth with
      attention-deficit/hyperactivity disorder: a review and recommendations for future
      research.
AB  - It is well established that children and adolescents with attention
      deficit/hyperactivity disorder (ADHD) frequently experience co-occurring mental
      health problems in addition to difficulties in their peer relationships. Although
      substantial research has focused on the extent to which peer functioning
      contributes to subsequent co-occurring mental health problems, much less research
      has considered how co-occurring mental health problems affect peer functioning
      domains. Therefore, the purpose of this review is to examine the effect of co
      occurring mental health problems on the peer functioning of youth with ADHD. The
      impact of co-occurring externalizing (i.e., oppositional defiant disorder,
      conduct disorder) and internalizing (i.e., anxiety, depression) symptoms are
      reviewed, with a focus on whether these co-occurring symptoms exacerbate,
      attenuate, or have no effect across peer domains of social skills/competence,
      peer status, and friendship among youth with ADHD. Drawing from a developmental
      psychopathology framework, this review then draws attention to relevant causal
      processes and developmental cascades (including social-cognitive, affective, and
      family and parenting factors) in offering promising avenues for future work.

PMID- 22965874
TI  - Encapsulation of photosensitizer into multilayer microcapsules by combination of
      spontaneous deposition and heat-induced shrinkage for photodynamic therapy.
AB  - Annealing of PDADMAC/PSS multilayer microcapsules assembled on PSS-doped CaCO(3)
      particles at 80  degrees C for 30 min reduces their size dramatically from 6.9 +/
      0.3 to 3.1 +/- 0.5 um. Methylene blue molecules are encapsulated by spontaneous
      deposition and post-annealing with a concentration of 22 mg . mL(-1), which is
      1000 times higher than the feeding value. The unreleased MB molecules are
      retained stably for a long time, which are then protected by the capsules against
      reductive enzymes and keep their photodynamic activity. The viability of HeLa
      cells incubated with the MB-loaded capsules decreases sharply from ~ 75 (dark
      cytotoxicity) to ~ 20% after irradiation with a laser at 671 nm and 60 J . cm(-2)
      for 75 s.

PMID- 22965873
TI  - Expression of the MAP kinase phosphatase DUSP4 is associated with microsatellite
      instability in colorectal cancer (CRC) and causes increased cell proliferation.
AB  - DUSP4 (MKP-2), a member of the mitogen-activated protein kinase phosphatase (MKP)
      family and potential tumor suppressor, negatively regulates the MAPKs (mitogen
      activated protein kinases) ERK, p38 and JNK. MAPKs play a crucial role in cancer
      development and progression. Previously, using microarray analyses we found a
      conspicuously frequent overexpression of DUSP4 in colorectal cancer (CRC) with
      high frequent microsatellite instability (MSI-H) compared to microsatellite
      stable (MSS) CRC. Here we studied DUSP4 expression on mRNA level in 38 CRC (19
      MSI-H and 19 MSS) compared to matched normal tissue as well as in CRC cell lines
      by RT-qPCR. DUSP4 was overexpressed in all 19 MSI-H tumors and in 14 MSS tumors.
      Median expression levels in MSI-H tumors were significantly higher than in MSS
      tumors (p < 0.001). Consistently, MSI-H CRC cell lines showed 6.8-fold higher
      DUSP4 mRNA levels than MSS cell lines. DUSP4 expression was not regulated by
      promoter methylation since no methylation was found by quantitative methylation
      analysis of DUSP4 promoter in CRC cell lines neither in tumor samples.
      Furthermore, no DUSP4 mutation was found on genomic DNA level in four CRC cell
      lines. DUSP4 overexpression in CRC cell lines through DUSP4 transfection caused
      upregulated expression of MAPK targets CDC25A, CCND1, EGR1, FOS, MYC and CDKN1A
      in HCT116 as well as downregulation of mismatch repair gene MSH2 in SW480.
      Furthermore, DUSP4 overexpression led to increased proliferation in CRC cell
      lines. Our findings suggest that DUSP4 acts as an important regulator of cell
      growth within the MAPK pathway and causes enhanced cell growth in MSI-H CRC.

PMID- 22965875
TI  - Substitutions at residue 211 in the prion protein drive a switch between CJD and
      GSS syndrome, a new mechanism governing inherited neurodegenerative disorders.
AB  - Human prion diseases are a heterogeneous group of fatal neurodegenerative
      disorders, characterized by the deposition of the partially protease-resistant
      prion protein (PrP(res)), astrocytosis, neuronal loss and spongiform change in
      the brain. Among inherited forms that represent 15% of patients, different
      phenotypes have been described depending on the variations detected at different
      positions within the prion protein gene. Here, we report a new mechanism
      governing the phenotypic variability of inherited prion diseases. First, we
      observed that the substitution at residue 211 with either Gln or Asp leads to
      distinct disorders at the clinical, neuropathological and biochemical levels
      (Creutzfeldt-Jakob disease or Gerstmann-Straussler-Scheinker syndrome with
      abundant amyloid plaques and tau neurofibrillar pathology). Then, using molecular
      dynamics simulations and biophysical characterization of mutant proteins and an
      in vitro model of PrP conversion, we found evidence that each substitution
      impacts differently the stability of PrP and its propensity to produce different
      protease resistant fragments that may contribute to the phenotypical switch.
      Thus, subtle differences in the PrP primary structure and stability are
      sufficient to control amyloid plaques formation and tau abnormal phosphorylation
      and fibrillation. This mechanism is unique among neurodegenerative disorders and
      is consistent with the prion hypothesis that proposes a conformational change as
      the key pathological event in prion disorders.

PMID- 22965876
TI  - Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in
      Huntington's disease mice: implications for the ubiquitin-proteasomal and
      autophagy systems.
AB  - We previously demonstrated that the histone deacetylase (HDAC) inhibitor, 4b,
      which preferentially targets HDAC1 and HDAC3, ameliorates Huntington's disease
      (HD)-related phenotypes in different HD model systems. In the current study, we
      investigated extensive behavioral and biological effects of 4b in N171-82Q
      transgenic mice and further explored potential molecular mechanisms of 4b action.
      We found that 4b significantly prevented body weight loss, improved several
      parameters of motor function and ameliorated Huntingtin (Htt)-elicited cognitive
      decline in N171-82Q transgenic mice. Pathways analysis of microarray data from
      the mouse brain revealed gene networks involving post-translational modification,
      including protein phosphorylation and ubiquitination pathways, associated with 4b
      drug treatment. Using real-time qPCR analysis, we validated differential
      regulation of several genes in these pathways by 4b, including Ube2K, Ubqln,
      Ube2e3, Usp28 and Sumo2, as well as several other related genes. Additionally, 4b
      elicited increases in the expression of genes encoding components of the
      inhibitor of kappaB kinase (IKK) complex. IKK activation has been linked to
      phosphorylation, acetylation and clearance of the Htt protein by the proteasome
      and the lysosome, and accordingly, we found elevated levels of phosphorylated
      endogenous wild-type (wt) Htt protein at serine 16 and threonine 3, and increased
      AcK9/pS13/pS16 immunoreactivity in cortical samples from 4b-treated mice. We
      further show that HDAC inhibitors prevent the formation of nuclear Htt aggregates
      in the brains of N171-82Q mice. Our findings suggest that one mechanism of 4b
      action is associated with the modulation of the ubiquitin-proteasomal and
      autophagy pathways, which could affect accumulation, stability and/or clearance
      of important disease-related proteins, such as Htt.

PMID- 22965877
TI  - NUB1 modulation of GSK3beta reduces tau aggregation.
AB  - Abnormal phosphorylation of the microtubule-associated protein tau in
      neurodegenerative disorders, including Alzheimer's disease (AD) and
      frontotemporal lobar degeneration, is associated with disrupted axonal transport
      and synaptic dysfunction ultimately manifesting as histopathological lesions of
      protein aggregates. Glycogen synthase kinase 3beta (GSK3beta) may be critical for
      the pathological hyperphosphorylation of tau. Here, we examined the role of the
      proteasome-associated protein Nedd8 ultimate buster 1 (NUB1) in the
      neuropathogenic phosphorylation and aggregation of tau. We reveal that NUB1
      interacted with both tau and GSK3beta to disrupt their interaction, and abolished
      recruitment of GSK3beta to tau inclusions. Moreover, NUB1 reduced GSK3beta
      mediated phosphorylation of tau and aggregation of tau in intracellular
      inclusions. Strikingly, NUB1 induced GSK3beta degradation. Deletion of the NUB1
      ubiquitin-like (UBL) domain did not impair the interaction with tau and GSK3beta,
      and the ability to suppress the phosphorylation and aggregation of tau was not
      affected. However, the UBL motif was necessary for GSK3beta degradation. Deletion
      of the NUB1 ubiquitin-associated (UBA) domain abrogated the ability of NUB1 to
      interact with and degrade GSK3beta. Moreover, the UBA domain was required to
      suppress the aggregation of tau. Silencing of NUB1 in cells stabilized endogenous
      GSK3beta and exacerbated tau phosphorylation. Thus, we propose that NUB1, by
      regulating GSK3beta levels, modulates tau phosphorylation and aggregation, and is
      a key player in neurodegeneration associated with tau pathology. Moreover, NUB1
      regulation of GSK3beta could modulate numerous signalling pathways in which
      GSK3beta is a centrally important effector.

PMID- 22965878
TI  - Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with
      disordered RhoA signalling, epithelial polarization and cytokinesis.
AB  - Inherited mutations in the folliculin (FLCN) gene cause the Birt-Hogg-Dube
      syndrome of familial hair follicle tumours (fibrofolliculomas), lung cysts and
      kidney tumours. Though folliculin has features of a tumour suppressor, the
      precise function of the FLCN gene product is not well characterized. We
      identified plakophilin-4 (p0071) as a potential novel folliculin interacting
      protein by yeast two-hybrid analysis. We confirmed the interaction of folliculin
      with p0071 by co-immunoprecipitation studies and, in view of previous studies
      linking p0071 to the regulation of rho-signalling, cytokinesis and intercellular
      junction formation, we investigated the effect of cell folliculin status on p0071
      related functions. Folliculin and p0071 partially co-localized at cell junctions
      and in mitotic cells, at the midbody during cytokinesis. Previously, p0071 has
      been reported to regulate RhoA signalling during cytokinesis and we found that
      folliculin deficiency was associated with increased expression and activity of
      RhoA and evidence of disordered cytokinesis. Treatment of folliculin-deficient
      cells with a downstream inhibitor of RhoA signalling (the ROCK inhibitor Y-27632)
      reversed the increased cell migration phenotype observed in folliculin-deficient
      cells. Deficiency of folliculin and of p0071 resulted in tight junction defects
      and mislocalization of E-cadherin in mouse inner medullary collecting duct-3
      renal tubular cells. These findings suggest that aspects of folliculin tumour
      suppressor function are linked to interaction with p0071 and the regulation of
      RhoA signalling.

PMID- 22965879
TI  - MMP1-1607 1G/2G polymorphism and lung cancer risk: a meta-analysis.
AB  - Matrix metalloproteinase-1 (MMP-1) plays an important role in the breakdown of
      extracellular matrix and mediates pathways of apoptosis, angiogenesis, and
      immunity. It has been demonstrated that MMP-1 overexpression is associated with
      tumor initiation, invasion, and metastasis. Many studies have investigated the
      association between MMP1-1607 1G/2G polymorphism and lung cancer risk, but the
      impact of MMP1-1607 1G/2G polymorphism on lung cancer is unclear owing to the
      obvious inconsistence among those studies. This study aimed to quantify the
      strength of the association between MMP1-1607 1G/2G polymorphism and lung cancer
      risk. We searched the PubMed, Embase, and Wanfang databases for studies on the
      association between MMP1-1607 1G/2G polymorphism and risk of lung cancer. We
      estimated summary odds ratio (OR) with its corresponding 95 % confidence interval
      (95%CI) to assess the association. Overall, MMP1-1607 1G/2G polymorphism was
      associated with increased risk of lung cancer under four genetic models (OR(2G
      versus 1G) = 1.21, 95 %CI 1.06-1.37; OR(2G2G versus 1G1G) = 1.36, 95%CI 1.09
      1.70; OR(2G2G versus 2G1G+1G1G) = 1.33, 95 %CI 1.10-1.61; and OR(2G2G+2G1G versus
      1G1G) = 1.15, 95 %CI 1.04-1.27). Meta-analyses of studies with high quality
      showed that MMP1-1607 1G/2G polymorphism was still associated with lung cancer
      risk under those four genetic models. Subgroup analyses by ethnicity and
      sensitivity analyses further identified the significant association in East
      Asians. No evidence of publication bias was observed. Meta-analyses of available
      data show a significant association between MMP1-1607 1G/2G polymorphism and lung
      cancer risk.

PMID- 22965880
TI  - RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of
      colorectal cancer.
AB  - In previous studies, we identified rhomboid domain containing 2 (RHBDD2) gene to
      be markedly overexpressed in breast cancer patients that developed recurrence of
      the disease. In this study, we evaluated for the first time RHBDD2 gene
      expression in colorectal cancer (CRC). Five public available DNA microarray
      studies were compiled in a homogeneous dataset of 906 colorectal samples. The
      statistical analysis of these data showed a significant increase of RHBDD2
      expression in the advanced stages of CRC (p < 0.01). We validated these findings
      by immunohistochemistry on 130 colorectal tissue samples; RHBDD2 protein
      overexpression was also observed in the advanced stages of the disease (p <
      0.001). In addition, we investigated RHBDD2 expression in response to the
      chemotherapy agent 5-fluorouracile (5FU). We detected a significant increase of
      RHBDD2 mRNA and protein after 5FU treatment (20-40 MUM; p < 0.001). Overall,
      these results showed that RHBDD2 overexpression might play a role in colorectal
      cancer progression.

PMID- 22965881
TI  - Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in
      liver cancer patients receiving transarterial chemoembolization therapy.
AB  - Transarterial chemoembolization (TACE) therapy is an effective locoregional
      anticancer treatment for liver cancer patients. Serum biomarkers involved in
      immunogenic cell death may be valuable for early predicting therapy response and
      estimating prognosis. Sera of 50 prospectively and consecutively included
      hepatocellular carcinoma (HCC) patients, undergoing TACE therapy, were taken
      before and 24 h after TACE application. In these samples, soluble biomarkers
      involved in immunogenic cell death, and among them, high-mobility group box 1
      (HMGB1), soluble receptor of advanced glycation end products (sRAGE), and DNase
      activity were measured. They were compared with radiological response to therapy.
      A total of 71 TACE therapies were evaluated, of which 32 were classified as "no
      progression," and 39, as "progression." While HMGB1 levels increased already 24 h
      after TACE, there was an early decrease of sRAGE and DNase activity.
      Pretherapeutic and 24-h values of sRAGE were significantly higher in the no
      progression group than those in the progression group. There was no difference
      with respect to treatment response for DNase and HMGB1. Soluble RAGE is a new
      parameter with predictive relevance in primary liver cancer patients undergoing
      TACE therapy.

PMID- 22965882
TI  - Increased platelet count is an indicator of metastasis in patients with
      nasopharyngeal carcinoma.
AB  - This study aims to evaluate the impact of pretreatment thrombocytosis on survival
      in patients with nasopharyngeal carcinoma (NPC). The data of 1,582 patients with
      NPC, who underwent definitive treatment between 2003 and 2004, were
      retrospectively reviewed. The correlation between the clinicopathological
      variables and the platelet count was analyzed. The prognostic significance of
      thrombocytosis, together with various clinicopathological factors, was evaluated
      by univariate and multivariate analyses. Platelet count showed significant
      correlation with gender, clinical stage, and T stage in univariate analysis.
      There was poorer 5-year disease-specific survival (DSS) in the patients with
      thrombocytosis than in those without thrombocytosis (70 vs. 78 %; p = 0.001) and
      poorer metastases-free survival (MFS) (81 vs. 88 %; p = 0.006). Univariate and
      multivariate analyses showed that thrombocytosis was an independent prognostic
      factor for MFS and DSS. Thrombocytosis is a useful predictor of metastasis and
      poor prognosis in patients with NPC.

PMID- 22965884
TI  - In response to wire grill brush bristle as an unusual foreign body: Report of two
      pediatric cases.

PMID- 22965883
TI  - Three prognostic factors influence clinical outcomes of primary testicular
      lymphoma.
AB  - The standard treatment of primary testicular lymphoma (PTL) has not been well
      established. Our study aimed to evaluate the relationship between the prognostic
      factors and clinical outcomes of PTL. We retrospectively reviewed the clinical
      records of 43 PTL patients and included the 39 patients who were diagnosed with
      primary testicular diffuse large B cell lymphoma (DLBCL) for analysis of
      prognostic factors and assessment of treatment modalities. Cox regression
      analysis showed that poor ECOG performance status (PS, >=2), infiltration of
      adjacent tissues (spermatic cord, epididymis, or scrotum), and bulky disease
      (tumor mass, >9 cm) were independent predictors of worse overall survival (OS)
      for primary testicular DLBCL. According to these three factors, the patients were
      divided into two groups. Rituximab was found to significantly prolong progression
      free survival (PFS) in the low-risk group (P = 0.044) but not in the high-risk
      group (P = 0.748). And the combination therapy for CNS prophylaxis significantly
      prolonged the survival in the high-risk group (P = 0.005 for OS; P = 0.004 for
      PFS), but not in the low-risk group (P = 0.092 for OS; P = 0.191 for PFS). ECOG
      performance status, infiltration of adjacent tissues, and bulky disease are
      practical prognostic factors of survival in patients with primary testicular
      DLBCL. The addition of rituximab is more important for the patients without the
      prognostics factors, and the combination CNS prophylaxis is more significant for
      the patients with the prognostics factors.

PMID- 22965886
TI  - A new dimension in separation science: comprehensive two-dimensional gas
      chromatography.
AB  - The introduction and development of comprehensive two-dimensional gas
      chromatography offers greatly enhanced resolution and identification of organic
      analytes in complex mixtures compared to any one-dimensional separation
      technique. Initially promoted by the need to resolve highly complex petroleum
      samples, the technique's enormous separation power and enhanced ability to gather
      information has rapidly attracted the attention of analysts from all scientific
      fields. In this Minireview, we highlight the fundamental theory, recent advances,
      and future trends in the instrumentation and application of comprehensive two
      dimensional column separation.

PMID- 22965887
TI  - Plasma cytokines in polycythemia vera: phenotypic correlates, prognostic
      relevance, and comparison with myelofibrosis.
AB  - Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates
      with disease phenotype and prognosis. In this study, we show that several plasma
      cytokines are also abnormally expressed in polycythemia vera (PV; n = 65),
      compared to normal controls (n = 35), but with a significantly different pattern
      than that of PMF (n = 127). Direct phenotypic correlation in PV included levels
      of IL-12 with hematocrit; IL-1b, IL-2, IL-7, FGF-b, and HGF with leukocytosis;
      and IFN-alpha and IFN-gamma with thrombocytosis. In univariate analysis, levels
      of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP-1beta
      remained significant on multivariable analysis that included the other cytokines
      as covariates. Increased level of MIP-1beta (P < 0.01), older age (P < 0.01), and
      leukocytosis (P = 0.03) maintained their association with shortened survival, on
      multivariable analysis. This study provides preliminary observations that warrant
      a larger scale study and suggests the value of plasma cytokines as prognostic
      biomarkers in PV.

PMID- 22965888
TI  - Development of ocular vestibular-evoked myogenic potentials in small children.
AB  - OBJECTIVES/HYPOTHESIS: This study investigated the development of otolithic
      ocular reflex in small children (<3 years old) via the ocular vestibular-evoked
      myogenic potential (oVEMP) test. STUDY DESIGN: Prospective study. METHODS: Twenty
      full-term newborns (group A), 15 children aged 1 to 3 years (group B), and 15
      children aged 4 to 13 years (group C) were enrolled in this study. All children
      underwent auditory brainstem response testing or audiometry, and the oVEMP test.
      RESULTS: All subjects had normal hearing. Typical biphasic oVEMP waveforms were
      not observed in the 20 newborns, but were present in six (40%) of 15 children
      aged 1 to 3 years and all (100%) children aged 4 to 13 years, exhibiting a
      significant difference. In group B, except for the nine children aged 12 to 24
      months, the remaining six children, aged 25 to 47 months, had clear oVEMPs, with
      the mean nI latency and nI-pI amplitude resembling those in children aged 4 to 13
      years, indicating that the otolithic-ocular reflex is mature in children aged >2
      years. CONCLUSIONS: Despite the well-developed caloric and cervical VEMP
      responses in early life, oVEMPs are not present in newborns, but are present in
      children aged >2 years who can walk with a gait resembling an adult. Maturation
      of the otolithic-ocular reflex is important to balance control, which is
      necessary in small children for independent gait.

PMID- 22965889
TI  - Early-stage squamous cell carcinoma of the lip: the Australian experience and the
      benefits of radiotherapy in improving outcome in high-risk patients after
      resection.
AB  - BACKGROUND: The purpose of this study was to analyze the outcome of Australian
      patients treated for early lip cancer. METHODS: Data on 217 patients with T1 to
      T2 squamous cell carcinoma (SCC) of the lip and treated with radical intent were
      analyzed. RESULTS: The addition of local adjuvant radiotherapy in patients with a
      close/positive margin was associated with a significant improvement in relapse
      free survival (RFS; p = .008). Tumor thickness (<=4 mm vs >4 mm) was also
      significantly associated with RFS (p = .01). The 5-year RFS was 51% after
      surgery, 87% after radiotherapy, and 92% after adjuvant radiotherapy.
      CONCLUSIONS: Patients with a tumor thickness >4 mm experienced an increased risk
      of recurrence, especially nodal. Compared with patients having any radiotherapy,
      those undergoing surgery experienced a higher rate of locoregional recurrence.
      The addition of adjuvant radiotherapy in patients with inadequate excision
      significantly decreased the risk of recurrence.

PMID- 22965890
TI  - Differences in drug approval processes of 3 regulatory agencies: a case study of
      gemtuzumab ozogamicin.
AB  - Major discrepancies concerning risk-benefit assessments and regulatory actions
      are frequent among regulatory agencies. We explored the differences by
      scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid
      leukaemia (AML). Assessment reports of GO were retrieved form the websites of the
      US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and
      Japanese regulatory agency, and we also reviewed published clinical trials. While
      GO was approved by the US FDA under the accelerated approval program in 2000, it
      was withdrawn from the market in 2010, based on the required post-marketing
      commitment failure. The EMA refused granting marketing authorization for GO in
      2008 on the grounds that there were no randomised controlled trials (RCTs). GO
      was approved as an orphan drug in Japan in 2005, and the Japanese regulatory
      authority decided to continue with the approval in 2010 on the condition that
      post-marketing surveillance is strengthened. Under these situations, promising
      new results of RCTs appeared in 2011, and the role of GO in AML treatment was
      refocused worldwide. The stringent regulation may not be suitable in case of an
      orphan drug of targeted therapy, and more room should be kept to facilitate
      effective developments of new anti-neoplastic agents.

PMID- 22965891
TI  - Loop prediction for a GPCR homology model: algorithms and results.
AB  - We present loop structure prediction results of the intracellular and
      extracellular loops of four G-protein-coupled receptors (GPCRs): bovine rhodopsin
      (bRh), the turkey beta1-adrenergic (beta1Ar), the human beta2-adrenergic
      (beta2Ar) and the human A2a adenosine receptor (A2Ar) in perturbed environments.
      We used the protein local optimization program, which builds thousands of loop
      candidates by sampling rotamer states of the loops' constituent amino acids. The
      candidate loops are discriminated between with our physics-based, all-atom energy
      function, which is based on the OPLS force field with implicit solvent and
      several correction terms. For relevant cases, explicit membrane molecules are
      included to simulate the effect of the membrane on loop structure. We also
      discuss a new sampling algorithm that divides phase space into different regions,
      allowing more thorough sampling of long loops that greatly improves results. In
      the first half of the paper, loop prediction is done with the GPCRs'
      transmembrane domains fixed in their crystallographic positions, while the loops
      are built one-by-one. Side chains near the loops are also in non-native
      conformations. The second half describes a full homology model of beta2Ar using
      beta1Ar as a template. No information about the crystal structure of beta2Ar was
      used to build this homology model. We are able to capture the architecture of
      short loops and the very long second extracellular loop, which is key for ligand
      binding. We believe this the first successful example of an RMSD validated,
      physics-based loop prediction in the context of a GPCR homology model.

PMID- 22965892
TI  - Design of a cellular-uptake-shielding magnetic catcher for cancer cell
      separation.
AB  - Fluorescent-magnetic-biotargeting multifunctional microcapsules (FMBMMs) are
      designed and fabricated via layer-by-layer assembly. It is found that the
      arginine-glycine-aspartate-modified FMBMMs were capable of sensitively detecting
      and efficiently isolating approximately 80% target cancer cells within 20 min.
      More importantly, FMBMMs present a general template for identifying and
      separating multiple types of cancer cells simply by altering the recognition
      motif.

PMID- 22965893
TI  - Declining liver utilization for transplantation in the United States and the
      impact of donation after cardiac death.
AB  - Worsening donor liver quality resulting in decreased organ utilization may be
      contributing to the recent decline in liver transplants nationally. We sought to
      examine trends in donor liver utilization and the relationship between donor
      characteristics and nonuse. We used the United Network for Organ Sharing database
      to review all deceased adult organ donors in the United States from whom at least
      1 solid organ was transplanted into a recipient. Trends in donor characteristics
      were examined. Multivariate logistic regression was used to evaluate the
      association between donor characteristics and liver nonuse between 2004 and 2010.
      Population attributable risk proportions were determined for donor factors
      associated with nonuse. We analyzed 107,259 organ donors. The number of unused
      livers decreased steadily from 1958 (66% of donors) in 1988 to 841 (15%) in 2004
      but then gradually increased to 1345 (21%) in 2010. The donor age, the body mass
      index (BMI), and the prevalence of diabetes and donation after cardiac death
      (DCD) all increased over time, and all 4 factors were independently associated
      with liver nonuse. DCD had the highest adjusted odds ratio (OR) for nonuse, and
      the odds increased nearly 4-fold between 2004 [OR = 5.53, 95% confidence interval
      (CI) = 4.57-6.70] and 2010 (OR = 21.31, 95% CI = 18.30-24.81). The proportion of
      nonuse attributable to DCD increased from 9% in 2004 to 28% in 2010. In
      conclusion, the proportion of donor livers not used has increased since 2004.
      Older donor age, greater BMI, diabetes, and DCD are all independently associated
      with nonuse and are on the rise nationally. Current trends may lead to
      significant declines in liver transplant availability.

PMID- 22965894
TI  - Time series analysis for the estimation of tidal fluctuation effect on different
      aquifers in a small coastal area of Saijo plain, Ehime prefecture, Japan.
AB  - Considering the current poor understanding of the seawater-freshwater (SW-FW)
      interaction pattern at dynamic hydro-geological boundary of coastal aquifers,
      this work strives to study tidal effect on groundwater quality using chemical
      tracers combined with environmental isotopes. In situ measurement data of
      electrical conductivity and groundwater level along with laboratory measurement
      data of hydro-chemical species were compared with tidal level data measured by
      Hydrographic and Oceanographic Department, Saijo City, Japan for time series
      analysis. Result shows that diurnal tides have significant effect on groundwater
      level as well as its chemical characteristics; however, the magnitude of effect
      is different in case of different aquifers. Various scatter diagrams were plotted
      in order to infer mechanisms responsible for water quality change with tidal
      phase, and results show that cations exchange, selective movement and local SW-FW
      mixing were likely to be the main processes responsible for water quality
      changes. It was also found that geological structure of the aquifers is the most
      important factor affecting the intensity of tidal effect on water quality.

PMID- 22965895
TI  - Levels and distribution of trace metals in surface sediments from Kongsfjorden,
      Svalbard, Norwegian Arctic.
AB  - Trace metal contents (Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb and Zn) have been measured
      in 27 surface sediment samples collected from Kongsfjorden, Svalbard, Norwegian
      Arctic. The analyses yielded concentration values (in mg kg(-1)) of 0.13-0.63 for
      Cd, 11.89-21.90 for Co, 48.65-81.84 for Cr, 21.26-36.60 for Cu, 299.59-683.48 for
      Mn, 22.43-35.39 for Ni, 10.68-36.59 for Pb, 50.28-199.07 for Zn and 8.09-65.34
      for Hg (in ng g(-1)), respectively. Relative cumulative frequency method has been
      used to define the baseline values of these metals, which (in mg kg(-1)) were
      0.14 for Cd, 13.56 for Co, 57.86 for Cr, 25.14 for Cu, 364.08 for Mn, 26.22 for
      Ni, 17.46 for Pb, 70.49 for Zn and 9.76 for Hg (in ng g(-1)), respectively. The
      enrichment factor analysis indicated that Hg showed some extent of anthropogenic
      pollution, while Pb, Zn and Cd showed limited anthropogenic contamination in the
      study areas.

PMID- 22965896
TI  - Acute ischemia of the parotid gland and auricle following embolization for
      epistaxis.
AB  - We report a case of ischemia of the auricle and acute parotitis that developed
      following embolization for epistaxis. A 53-year-old male was previously
      conservatively treated for epistaxis with bilateral posterior nasal packing due
      to hypertension. As the bleeding, continued the patient underwent bilateral
      embolization of the internal maxillary arteries. The bleeding was controlled but
      the patient developed acute ischemia of the ipsilateral parotid gland and the
      auricle that regressed with medical treatment.

PMID- 22965897
TI  - Alterations in purine metabolism in middle-aged elite, amateur, and recreational
      runners across a 1-year training cycle.
AB  - Changes in purine derivatives may be considered as signs of training-induced
      metabolic adaptations. The purpose of this study was to assess the effect of a 1
      year training cycle on the response of hypoxanthine (Hx) concentration and Hx
      guanine phosphoribosyltransferase (HGPRT) activity. Three groups of middle-aged
      male runners were examined: 11 elite master runners (EL; 46.0 +/- 3.8 years), 9
      amateur runners (AM; 45.1 +/- 4.7 years), and 10 recreational runners (RE; 45.9
      +/- 6.1 years). Plasma Hx concentration and erythrocyte HGPRT activity were
      measured in three characteristic training phases of the annual cycle. Significant
      differences in post-exercise Hx concentration and resting HGPRT activity were
      demonstrated between the EL, AM, and RE groups across consecutive training
      phases. The EL group showed lowest Hx concentration and highest HGPRT activity
      compared to the AM and RE groups. Analogous differences were observed between the
      AM and RE groups during specific preparation. For the EL group, the changes were
      observed across all examinations and the lowest Hx concentration and highest
      HGPRT activity were found in the competition phase. Significant change was also
      revealed in the AM group between the general and specific preparation, but not in
      the competition phase. No significant changes were found in the RE runners who
      did not use anaerobic exercise in their training. In conclusion, a long-lasting
      endurance training, incorporating high-intensity exercise, results in significant
      changes in purine metabolism, whereas training characterized by constant low
      intensity exercise does not. Plasma Hx concentration and erythrocyte HGPRT
      activity may be sensitive indicators of training adaptation and training status
      in middle-aged athletes.

PMID- 22965898
TI  - Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B
      adenosine receptors.
AB  - OBJECTIVES/HYPOTHESIS: Mucociliary clearance (MCC) is an important mechanism of
      host defense in the upper and lower respiratory tract. Impaired MCC plays a
      critical role in the development and perpetuation of chronic rhinosinusitis
      (CRS). The aim of this investigation was to determine the influence of adenosine
      on nasal MCC, and to determine the receptors mediating this physiology in vivo.
      STUDY DESIGN: Prospective study using an animal model. METHODS: Nasal MCC was
      measured by whole-nose scintigraphic acquisition in vivo. The effects of both
      endogenous and exogenous adenosine were investigated in wild-type and adenosine
      receptor knockout (A(2A)(-/-), A(2B)(-/-), A(2A)(-/-)A(2B)(-/-), and A(1)(-/-
      )A(3)(-/-)) mice. RESULTS: Exogenous adenosine aerosol robustly enhanced nasal
      MCC. The augmentation of MCC by adenosine was abolished in mice lacking both
      A(2A) and A(2B) receptors, but remained robust in mice lacking either A(2A) or
      A(2B) . Likewise, basal nasal MCC was reduced in mice lacking both the A(2A) and
      A(2B) receptors, but was statistically identical among wild-type mice and mice
      lacking either A(2A) or A(2B) . CONCLUSIONS: These findings indicate that
      activation of both G(s) -coupled adenosine receptors can accelerate nasal MCC.
      Targeting these receptors may represent a novel therapeutic approach for
      enhancing MCC in CRS.

PMID- 22965899
TI  - Clinical expression in Pfeiffer syndrome type 2 and 3: surveillance in Japan.
AB  - Pfeiffer syndrome (PS) is a classic type of craniosynostosis syndrome. Severe
      cases usually require emergency care at birth. However, early diagnosis is often
      precluded by the rarity and consequent low awareness of this disease. This study
      aimed to clarify phenotypic expressions useful for the diagnosis of PS. We
      reviewed all cases of PS type 2 or 3 according to Cohen's classification that
      were reported between 1980 and 2011 in Japan. Clinical and genetic information
      were extracted from the patients' medical records. A total of 23 patients with PS
      type 2 or 3 were identified. All 23 patients presented with craniosynostosis,
      midface hypoplasia, proptosis, broad thumbs, and wide great toes. FGFR2 mutations
      were confirmed in all 8 patients in whom genetic analyses were performed. In
      addition to classic symptoms, elbow ankylosis and sacrococcygeal defects were
      present in 70% and 30% of the patients, respectively. During an average follow-up
      of 22 months, 22% of patients died before 1 year of age. Elbow ankylosis and
      sacrococcygeal defects were the phenotypic features recognizable at a glance.
      These defects strongly suggest the presence of PS in newborns with
      craniosynostosis.

PMID- 22965900
TI  - Challenges facing lithium batteries and electrical double-layer capacitors.
AB  - Energy-storage technologies, including electrical double-layer capacitors and
      rechargeable batteries, have attracted significant attention for applications in
      portable electronic devices, electric vehicles, bulk electricity storage at power
      stations, and "load leveling" of renewable sources, such as solar energy and wind
      power. Transforming lithium batteries and electric double-layer capacitors
      requires a step change in the science underpinning these devices, including the
      discovery of new materials, new electrochemistry, and an increased understanding
      of the processes on which the devices depend. The Review will consider some of
      the current scientific issues underpinning lithium batteries and electric double
      layer capacitors.

PMID- 22965901
TI  - Mechanism of the initiation of mRNA decay: role of eRF3 family G proteins.
AB  - mRNA decay is intimately linked to and regulated by translation in eukaryotes.
      However, it has remained unclear exactly how mRNA decay is linked to translation.
      Progress has been made in recent years in understanding the molecular mechanisms
      of the link between translation and mRNA decay. It has become clear that the eRF3
      family of GTP-binding proteins acts as signal transducers that couple translation
      to mRNA decay and plays pivotal roles in the regulation of gene expression and
      mRNA quality control. During translation, the translation termination factor eRF3
      in complex with eRF1 recognizes the termination codon which appears at the A site
      of the terminating ribosome. Depending on whether the termination codon is normal
      (bona fide) or aberrant (premature), deadenylation-dependent decay or nonsense
      mediated mRNA decay (NMD) occurs. mRNA without termination codons and mRNA with
      the propensity to cause the ribosome to stall are recognized as aberrant by other
      members of the eRF3 family during translation, and these translational events
      cause nonstop mRNA decay (NSD) and no-go decay (NGD), respectively. In this
      review, we focus on how mRNA decay is triggered by translational events and
      summarize the initiation mechanism for the decay of both normal and aberrant
      mRNAs.

PMID- 22965902
TI  - Metastatic papillary thyroid cancer with lateral neck disease: pattern of spread
      by level.
AB  - BACKGROUND: Currently, there is no clear consensus on the extent of this lateral
      neck dissection required in papillary thyroid cancer (PTC) with lateral neck
      metastasis. The purpose of this study was to review our experience with
      metastatic PTC, and identify the pattern of lymphatic spread to the lateral neck.
      METHODS: A retrospective medical chart review of PTC patients treated with
      lateral neck dissection (levels II-Vb) at our institution between January 2004
      and 2011. A total of 185 patients underwent 248 selective lateral neck
      dissections. RESULTS: Levels II, III, IV, and Vb were respectively involved in
      49.3%, 76.6%, 61.6%, and 29.2% of cases. CONCLUSION: We advocate for a routine
      excision of levels II, III, IV, and Vb in PTC with metastasize to any lateral
      neck level. Although we have routinely dissected level IIb, it may be appropriate
      to omit its dissection, as well as level Va, when there are no clinical,
      radiologic, or intraoperative evidence of disease involving these sublevels.

PMID- 22965903
TI  - Factors that affect deceased donor liver transplantation rates in the United
      States in addition to the Model for End-stage Liver Disease score.
AB  - Under an ideal implementation of Model for End-Stage Liver Disease (MELD)-based
      liver allocation, the only factors that would predict deceased donor liver
      transplantation (DDLT) rates would be the MELD score, blood type, and donation
      service area (DSA). We aimed to determine whether additional factors are
      associated with DDLT rates in actual practice. Data from the Scientific Registry
      of Transplant Recipients for all adult candidates wait-listed between March 1,
      2002 and December 31, 2008 (n = 57,503) were analyzed. Status 1 candidates were
      excluded. Cox regression was used to model covariate-adjusted DDLT rates, which
      were stratified by the DSA, blood type, liver-intestine policy, and allocation
      MELD score. Inactive time on the wait list was not modeled, so the computed DDLT
      hazard ratios (HRs) were interpreted as active wait-list candidates. Many
      factors, including the candidate's age, sex, diagnosis, hospitalization status,
      and height, prior DDLT, and combined listing for liver-kidney or liver-intestine
      transplantation, were significantly associated with DDLT rates. Factors
      associated with significantly lower covariate-adjusted DDLT rates were a higher
      serum creatinine level (HR = 0.92, P < 0.001), a higher bilirubin level (HR =
      0.99, P = 0.001), and the receipt of dialysis (HR = 0.83, P < 0.001). Mild
      ascites (HR = 1.15, P < 0.001) and hepatic encephalopathy (grade 1 or 2, HR =
      1.05, P = 0.02; grade 3 or 4, HR = 1.10, P = 0.01) were associated with
      significantly higher adjusted DDLT rates. In conclusion, adjusted DDLT rates for
      actively listed candidates are affected by many factors aside from those integral
      to the allocation system; these factors include the components of the MELD score
      itself as well as candidate factors that were considered but were deliberately
      omitted from the MELD score in order to keep it objective. These results raise
      the question whether additional candidate characteristics should be explicitly
      incorporated into the prioritization of wait-list candidates because such factors
      are already systematically affecting DDLT rates under the current allocation
      system.

PMID- 22965905
TI  - DNA polymerase kappa microsatellite synthesis: two distinct mechanisms of
      slippage-mediated errors.
AB  - Microsatellite tandem repeats are frequent sites of strand slippage mutagenesis
      in the human genome. Microsatellite mutations often occur as insertion/deletion
      of a repeat motif (unit-based indels), and increase in frequency with increasing
      repeat length after a threshold is reached. We recently demonstrated that DNA
      polymerase kappa (Pol kappa) produces fewer unit-based indel errors within
      dinucleotide microsatellites than does polymerase delta. Here, we examined human
      Pol kappa's error profile within microsatellite alleles of varying sequence
      composition and length, using an in vitro HSV-tk gap-filling assay. We observed
      that Pol kappa displays relatively accurate synthesis for unit-based indels,
      using di- and tetranucleotide repeat templates longer than the threshold length.
      We observed an abrupt increase in the unit-based indel frequency when the total
      microsatellite length exceeds 28 nucleotides, suggesting that extended Pol kappa
      protein-DNA interactions enhance fidelity of the enzyme when synthesizing these
      microsatellite alleles. In contrast, Pol kappa is error-prone within the HSV-tk
      coding sequence, producing frequent single-base errors in a manner that is highly
      biased with regard to sequence context. Single-nucleotide errors are also created
      by Pol kappa within di- and tetranucleotide repeats, independently of the
      microsatellite allele length and at a frequency per nucleotide similar to the
      frequency of single base errors within the coding sequence. These single-base
      errors represent the mutational signature of Pol kappa, and we propose them a
      mechanism independent of homology-stabilized slippage. Pol kappa's dual fidelity
      nature provides a unique research tool to explore the distinct mechanisms of
      slippage-mediated mutagenesis.

PMID- 22965904
TI  - Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) is a subtype of B-cell Non-Hodgkin's Lymphoma (NHL)
      and accounts for ~6% of all lymphomas. MCL is highly refractory to most
      chemotherapy including newer antibody-based therapeutic approaches, and high
      grade MCL has one of the worst survival rates among NHLs. Therefore, the
      development of new therapeutic strategies to overcome drug resistance of MCL is
      important. In this article, we tested the effects of arsenic trioxide (As(2) O(3)
      , ATO) in bortezomib-resistant MCL. ATO is reported to induce complete remission
      in the patients with relapsed or refractory acute promyelocytic leukemia. Their
      effects in MCL, however, have not been explored. In this report, we show that ATO
      effectively inhibited the growth of MCL cells in vitro. ATO treatment also
      reduced cyclin D1 expression which is a genetic hallmark of MCL and NF-kB
      expression which was reported to have a prosurvival role in some MCL cells. The
      induction of apoptosis in MCL was partially due to reduced levels of cyclin D1
      and increased levels of apoptosis-related molecules. The antiproliferative
      effects of bortezomib on MCL greatly increased when the cells were also treated
      with ATO, indicating ATO can sensitize MCL to bortezomib. Similar results were
      noted in bortezomib-resistant cell lines. In conclusion, ATO may be an
      alternative drug for use in combined adjuvant therapies for MCL, and further
      clinical testing should be performed.

PMID- 22965906
TI  - Videofluoroscopic assessment of pharyngeal stage delay reflects pathophysiology
      after brain infarction.
AB  - OBJECTIVES/HYPOTHESIS: The pathophysiology of dysphagia caused by brain
      infarction varies with the site of the lesion in the brain. Patients with
      suprabulbar lesions have demonstrated delayed triggering of pharyngeal stage
      including delayed laryngeal elevation. Patients with severe pharyngeal stage
      delay have a high risk of intractable aspiration to the lower respiratory tract.
      Despite this, few studies have compared the pharyngeal stage delay with the
      lesion site. We defined a new temporal parameter of the pharyngeal stage delay to
      assess laryngeal elevation delay against the bolus inflow into the pharyngeal
      space. This study aimed to elucidate whether this parameter of pharyngeal stage
      delay is clinically useful to assess the pathophysiology of brain lesions after
      brain infarction. STUDY DESIGN: Case-control study. METHODS: Videofluoroscopic
      assessment of swallowing examinations was performed from January 7, 2000 to March
      29, 2011 at Kyushu University Hospital. We evaluated the pharyngeal stage delay
      using motion analysis on videofluoroscopic swallowing examination in patients
      with normal swallowing and brain infarction patients divided into
      pathophysiologic lesion groups. Laryngeal elevation delay time and pharyngeal
      delay time were analyzed. RESULTS: Significant differences in laryngeal elevation
      delay time were observed between each pathophysiologic lesion group. However,
      pharyngeal delay time remained similar among groups. Brain infarctions of
      corticobulbar tract and basal ganglion were significantly associated with
      laryngeal elevation delay time prolongation. CONCLUSIONS: Laryngeal elevation
      delay time with low-viscosity contrast medium is a recommended parameter to
      discriminate the corticobulbar tract and the basal ganglion lesion.

PMID- 22965907
TI  - Different cyclin types collaborate to reverse the S-phase checkpoint and permit
      prompt mitosis.
AB  - Precise timing coordinates cell proliferation with embryonic morphogenesis. As
      Drosophila melanogaster embryos approach cell cycle 14 and the midblastula
      transition, rapid embryonic cell cycles slow because S phase lengthens, which
      delays mitosis via the S-phase checkpoint. We probed the contributions of each of
      the three mitotic cyclins to this timing of interphase duration. Each pairwise
      RNA interference knockdown of two cyclins lengthened interphase 13 by introducing
      a G2 phase of a distinct duration. In contrast, pairwise cyclin knockdowns failed
      to introduce a G2 in embryos that lacked an S-phase checkpoint. Thus, the single
      remaining cyclin is sufficient to induce early mitotic entry, but reversal of the
      S-phase checkpoint is compromised by pairwise cyclin knockdown. Manipulating
      cyclin levels revealed that the diversity of cyclin types rather than cyclin
      level influenced checkpoint reversal. We conclude that different cyclin types
      have distinct abilities to reverse the checkpoint but that they collaborate to do
      so rapidly.

PMID- 22965908
TI  - Cell confinement controls centrosome positioning and lumen initiation during
      epithelial morphogenesis.
AB  - Epithelial organ morphogenesis involves sequential acquisition of apicobasal
      polarity by epithelial cells and development of a functional lumen. In vivo,
      cells perceive signals from components of the extracellular matrix (ECM), such as
      laminin and collagens, as well as sense physical conditions, such as matrix
      stiffness and cell confinement. Alteration of the mechanical properties of the
      ECM has been shown to promote cell migration and invasion in cancer cells, but
      the effects on epithelial morphogenesis have not been characterized. We analyzed
      the effects of cell confinement on lumen morphogenesis using a novel,
      micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture
      method. We show that cell confinement, by controlling cell spreading, limits
      peripheral actin contractility and promotes centrosome positioning and lumen
      initiation after the first cell division. In addition, peripheral actin
      contractility is mediated by master kinase Par-4/LKB1 via the RhoA-Rho kinase
      myosin II pathway, and inhibition of this pathway restores lumen initiation in
      minimally confined cells. We conclude that cell confinement controls nuclear
      centrosomal orientation and lumen initiation during 3D epithelial morphogenesis.

PMID- 22965909
TI  - Crumbs limits oxidase-dependent signaling to maintain epithelial integrity and
      prevent photoreceptor cell death.
AB  - Drosophila melanogaster Crumbs (Crb) and its mammalian orthologues (CRB1-3) share
      evolutionarily conserved but poorly defined roles in regulating epithelial
      polarity and, in photoreceptor cells, morphogenesis and stability. Elucidating
      the molecular mechanisms of Crb function is vital, as mutations in the human CRB1
      gene cause retinal dystrophies. Here, we report that Crb restricts Rac1-NADPH
      oxidase-dependent superoxide production in epithelia and photoreceptor cells.
      Reduction of superoxide levels rescued epithelial defects in crb mutant embryos,
      demonstrating that limitation of superoxide production is a crucial function of
      Crb and that NADPH oxidase and superoxide contribute to the molecular network
      regulating epithelial tissue organization. We further show that reduction of Rac1
      or NADPH oxidase activity or quenching of reactive oxygen species prevented
      degeneration of Crb-deficient retinas. Thus, Crb fulfills a protective role
      during light exposure by limiting oxidative damage resulting from Rac1-NADPH
      oxidase complex activity. Collectively, our results elucidate an important
      mechanism by which Crb functions in epithelial organization and the prevention of
      retinal degeneration.

PMID- 22965910
TI  - Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry
      and spindle orientation.
AB  - The cytoplasmic dynein motor generates pulling forces to center and orient the
      mitotic spindle within the cell. During this positioning process, dynein
      oscillates from one pole of the cell cortex to the other but only accumulates at
      the pole farthest from the spindle. Here, we show that dynein light chain 1
      (DYNLL1) is required for this asymmetric cortical localization of dynein and has
      a specific function defining spindle orientation. DYNLL1 interacted with a
      spindle-microtubule-associated adaptor formed by CHICA and HMMR via TQT motifs in
      CHICA. In cells depleted of CHICA or HMMR, the mitotic spindle failed to orient
      correctly in relation to the growth surface. Furthermore, CHICA TQT motif mutants
      localized to the mitotic spindle but failed to recruit DYNLL1 to spindle
      microtubules and did not correct the spindle orientation or dynein localization
      defects. These findings support a model where DYNLL1 and CHICA-HMMR form part of
      the regulatory system feeding back spindle position to dynein at the cell cortex.

PMID- 22965913
TI  - Methicillin-resistant and methicillin-sensitive Staphylococcus aureus laryngitis.
AB  - OBJECTIVES/HYPOTHESIS: Despite the fact that a wide variety of head and neck
      methicillin-resistant Staphylococcus aureus (MRSA) infections have been
      described, only four cases of MRSA laryngitis are reported in the literature. Our
      clinical experience suggests that this diagnosis is more common and can be more
      subtle that previously reported. The objective of this study was to identify and
      describe the clinical presentation, diagnosis, treatment, and outcomes of MRSA
      and methicillin-sensitive S aureus (MSSA) laryngitis, highlighting the in-office
      workup of these patients. STUDY DESIGN: Retrospective case series. METHODS: All
      patients with a culture-proven diagnosis of S aureus laryngitis treated within
      the Emory Voice Center, Department of Otolaryngology-Head and Neck Surgery at
      Emory University between 2007 and 2011. Demographic, diagnostic, and treatment
      data were retrospectively collected from the patients' hospital records. RESULTS:
      Three patients with culture-proven MRSA laryngitis were identified. Three further
      cases of MSSA were also identified. Patients ranged in age from 34 to 74 years.
      All three patients with MRSA were diabetics. All six patients in the study were
      current or past users of cigarettes. The most common presenting symptoms were
      vocal roughness, vocal fatigue, and decreased vocal endurance. There were no
      symptoms of airway or swallowing compromise. The duration of symptoms at the time
      of initial assessment ranged from 3 months to 5 years, and most patients had
      undergone numerous previous treatments. Common signs on laryngeal examination
      included thickened vocal fold epithelium, whitish debris or the appearance of
      leukoplakia, edema, and crusting. Signs and symptoms were similar in MRSA and
      MSSA patients. The diagnosis was made in all patients via awake in-office culture
      of the larynx. All patients were treated with a prolonged course of trimethoprim
      sulfamethoxazole (2-4 weeks). Although repeated courses of treatment were
      required, most patients had an excellent response to treatment. CONCLUSIONS: This
      is the largest, single, case series of patients with MRSA laryngitis. Our study
      findings suggest that the diagnosis may be more common than previously
      recognized, and that the presenting signs and symptoms may be subtle and similar
      to MSSA. Diagnosis can be made via in-office laryngeal culture. Clinicians must
      have a high index of suspicion for this diagnosis.

PMID- 22965912
TI  - Emerging facets of plastid division regulation.
AB  - Plastids are complex organelles that are integrated into the plant host cell
      where they differentiate and divide in tune with plant differentiation and
      development. In line with their prokaryotic origin, plastid division involves
      both evolutionary conserved proteins and proteins of eukaryotic origin where the
      host has acquired control over the process. The plastid division apparatus is
      spatially separated between the stromal and the cytosolic space but where clear
      coordination mechanisms exist between the two machineries. Our knowledge of the
      plastid division process has increased dramatically during the past decade and
      recent findings have not only shed light on plastid division enzymology and the
      formation of plastid division complexes but also on the integration of the
      division process into a multicellular context. This review summarises our current
      knowledge of plastid division with an emphasis on biochemical features, the
      functional assembly of protein complexes and regulatory features of the overall
      process.

PMID- 22965914
TI  - A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic
      twins with nephrogenic diabetes insipidus and intellectual disability.
AB  - The clinical features of loss of ARHGAP4 function remain unclear despite several
      reports of different patterns of deletions inactivating different functional
      regions of the protein. The protein encoded by ARHGAP4 is thought to function as
      a Rho GTPase activating protein. Characterization of the genetic defect causing X
      linked nephrogenic diabetes insipidus (NDI) and intellectual disability in two
      dizygotic twin brothers revealed a novel contiguous deletion of 17,905 bp
      encompassing the entire AVPR2 gene and extending into intron 7 of the ARHGAP4
      gene. Examination of their mother showed that she was a carrier of this deletion.
      An attempt was made to distinguish the putative clinical signs of an ARHGAP4
      deletion from the well-defined phenotype of X-linked NDI caused by an AVPR2 gene
      deletion. By reviewing all characterized deletions encompassing ARHGAP4, we
      reconsider the potential role of ARHGAP4 in cognition.

PMID- 22965911
TI  - Translocation of CaMKII to dendritic microtubules supports the plasticity of
      local synapses.
AB  - The processing of excitatory synaptic inputs involves compartmentalized dendritic
      Ca(2+) oscillations. The downstream signaling evoked by these local Ca(2+)
      transients and their impact on local synaptic development and remodeling are
      unknown. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an important
      decoder of Ca(2+) signals and mediator of synaptic plasticity. In addition to its
      known accumulation at spines, we observed with live imaging the dynamic
      recruitment of CaMKII to dendritic subdomains adjacent to activated synapses in
      cultured hippocampal neurons. This localized and transient enrichment of CaMKII
      to dendritic sites coincided spatially and temporally with dendritic Ca(2+)
      transients. We show that it involved an interaction with microtubular elements,
      required activation of the kinase, and led to localized dendritic CaMKII
      autophosphorylation. This process was accompanied by the adjacent remodeling of
      spines and synaptic AMPA receptor insertion. Replacement of endogenous CaMKII
      with a mutant that cannot translocate within dendrites lessened this activity
      dependent synaptic plasticity. Thus, CaMKII could decode compartmental dendritic
      Ca(2+) transients to support remodeling of local synapses.

PMID- 22965915
TI  - The carboxylate twist: hysteretic bistability of a high-spin diiron(II) complex
      identified by Mossbauer spectroscopy.

PMID- 22965916
TI  - Autologous bone marrow stromal cells loaded onto porous gelatin scaffolds
      containing Drynaria fortunei extract for bone repair.
AB  - GGT-GSB composite was prepared by mixing a biodegradable GGT composite containing
      genipin-crosslinked gelatin and beta-tricalcium phosphate with Gu-Sui-Bu extract
      (GSB) (Drynaria fortunei (Kunze) J. Sm.), a traditional Chinese medicine. Then,
      porous GGT and GGT-GSB scaffolds were fabricated using a salt-leaching method.
      The GGT and GGT-GSB scaffolds thus obtained had a macroporous structure and high
      porosity. Rabbit bone marrow stromal cells (BMSCs) were seeded onto GGT and GGT
      GSB scaffolds. The biological response of rabbit calvarial bone to these
      scaffolds was considered to evaluate the potential of the scaffolds for use in
      bone tissue engineering. After 8 weeks of implantation, each scaffold induced new
      bone formation at a cranial bone defect, as was verified by X-ray
      microradiography. The BMSC-seeded GGT-GSB scaffolds induced more new bone
      formation than the BMSC-seeded GGT and acellular scaffolds. These observations
      suggest that an autologous BMSCs-seeded porous GGT-GSB scaffold can be adopted in
      bone engineering in vivo and has great potential for regenerating defective bone
      tissue.

PMID- 22965917
TI  - Squamous cell carcinoma of the oral tongue in a patient with Fanconi anemia
      treated with radiotherapy and concurrent cetuximab: a case report and review of
      the literature.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder
      characterized by bone marrow failure and increased risk of cancers including
      acute myelogenous leukemia and various solid tumors, especially head and neck
      cancer. Management of head and neck cancer in the setting of FA is complicated by
      pancytopenia, poor tolerance of chemotherapy, and potentially increased
      radiosensitivity. There are limited reports on tolerance of radiotherapy (RT) in
      patients with FA. METHODS: We report a case of a patient with FA who presented
      with a small oral tongue cancer that was excised. He rapidly developed extensive
      locoregional recurrence and underwent surgical resection followed by
      postoperative RT with concurrent cetuximab. RESULTS: Both RT and cetuximab were
      well tolerated with manageable toxicities. Unfortunately, the patient died of
      early locoregional disease progression. CONCLUSIONS: RT with concurrent cetuximab
      was well tolerated and may be an appropriate option in patients with FA. However,
      many patients have a poor prognosis due to aggressive disease.

PMID- 22965918
TI  - Haloalkane dehalogenases: biotechnological applications.
AB  - Haloalkane dehalogenases (EC 3.8.1.5, HLDs) are alpha/beta-hydrolases which act
      to cleave carbon-halogen bonds. Due to their unique catalytic mechanism, broad
      substrate specificity and high robustness, the members of this enzyme family have
      been employed in several practical applications: (i) biocatalytic preparation of
      optically pure building-blocks for organic synthesis; (ii) recycling of by
      products from chemical processes; (iii) bioremediation of toxic environmental
      pollutants; (iv) decontamination of warfare agents; (v) biosensing of
      environmental pollutants; and (vi) protein tagging for cell imaging and protein
      analysis. This review discusses the application of HLDs in the context of the
      biochemical properties of individual enzymes. Further extension of HLD uses
      within the field of biotechnology will require currently limiting factors - such
      as low expression, product inhibition, insufficient enzyme selectivity, low
      affinity and catalytic efficiency towards selected substrates, and instability in
      the presence of organic co-solvents - to be overcome. We propose that strategies
      based on protein engineering and isolation of novel HLDs from extremophilic
      microorganisms may offer solutions.

PMID- 22965919
TI  - The differences and correlations of BCR-ABL transcripts between peripheral blood
      and bone marrow assays are associated with the molecular responses in the bone
      marrow for chronic myelogenous leukemia.
AB  - Previous studies concerning BCR-ABL mRNA levels by quantitative real-time RT-PCR
      (Q-PCR) for chronic myelogenous leukemia (CML) have shown a significant
      concordance between peripheral blood (PB) and bone marrow (BM) assays. The
      objective of this study was to determine whether molecular monitoring using PB
      was comparable to using BM for CML. A comparative study was performed that
      analyzed the Q-PCR results of 712 simultaneous PB and BM samples from 330
      patients before and during imatinib therapy. For the 78 paired pretreatment
      samples, the level of BCR-ABL mRNA in PB was lower than that in BM (P = 0.007).
      Although the overall amounts of BCR-ABL mRNA in the PB and BM were comparable (P=
      0.072) and there was a strong correlation (r = 0.839, P < 0.001) with the 634
      paired on-treatment samples, the depth of the molecular response in PB was lower
      than that in BM (P < 0.001). The level of BCR-ABL mRNA in PB was lower than that
      in BM where the BM BCR-ABL mRNA < 1 log reduction (P < 0.001) or >= 1-< 2 log
      reductions (P = 0.008) from the baseline, and higher than that where the BM BCR
      ABL mRNA >= 2 log-reductions (P < 0.001). A strong correlation (r = 0.811, P <
      0.001) was only found where the BM BCR-ABL mRNA < 1 log reduction. We conclude
      that the differences and correlations of BCR-ABL mRNA between PB and BM assays
      depend on the depth of the molecular response in BM for CML during imatinib
      therapy.

PMID- 22965920
TI  - A selenium-based cathode for a high-voltage tandem photoelectrochemical solar
      cell.

PMID- 22965921
TI  - Self-rated right-left confusability and performance on the Money Road-Map Test.
AB  - This study assessed the relationship between self-rated right-left confusability
      and performance on the Money Road-Map Test (MRMT). Eighty-six undergraduate
      university students (44 women and 42 men) rated right-left subjective
      confusability using a questionnaire, and then completed the MRMT. Low- and high
      confusability groups were determined using self-rated confusability scores. The
      high-confusability participants were less accurate and slower than the low
      confusability participants in completing the MRMT. Self-confusability ratings
      significantly correlated with both accuracy scores and completion times on the
      MRMT. Although, women showed a significantly greater inclination than men to
      judge themselves as being more prone to confusion in right-left discrimination,
      the male advantage was not observed in terms of accuracy of response: there was a
      significant difference only in the completion time on the MRMT. 

PMID- 22965922
TI  - DNA polymerase zeta generates clustered mutations during bypass of endogenous DNA
      lesions in Saccharomyces cerevisiae.
AB  - Multiple sequence changes that are simultaneously introduced in a single DNA
      transaction have a higher probability of altering gene function than do single
      base substitutions. DNA polymerase zeta (Pol zeta) has been shown to introduce
      such clustered mutations under specific selective and/or DNA damage-producing
      conditions. In this study, a forward mutation assay was used to determine the
      specificity of spontaneous mutations generated in Saccharomyces cerevisiae when
      either wild-type Pol zeta or a mutator Pol zeta variant (rev3-L979F) bypasses
      endogenous lesions. Mutagenesis in strains proficient for nucleotide excision
      repair (NER) was compared to mutagenesis in NER-deficient strains that retain
      unrepaired endogenous DNA lesions in the genome. Compared to NER-proficient
      strains, NER-deficient rad14Delta strains have elevated mutation rates that
      depend on Pol zeta. Rates are most strongly elevated for tandem base pair
      substitutions and clusters of multiple, closely spaced mutations. Both types of
      mutations depend on Pol zeta, but not on Pol eta. Rates of each are further
      elevated in yeast strains bearing the rev3-979F allele. The results indicate that
      when Pol zeta performs mutagenic bypass of endogenous, helix-distorting lesions,
      it catalyzes a short track of processive, error-prone synthesis. We discuss the
      implications of this unique catalytic property of Pol zeta to its evolutionary
      conservation and possibly to multistage carcinogenesis.

PMID- 22965924
TI  - Giant papillary carcinoma arising in the ectopic buccal thyroid tissue.
AB  - BACKGROUND: Ectopic thyroid tissue very rarely occurs in the buccal region. Even
      more rarely encountered is the papillary carcinoma arising in the ectopic tissue.
      METHODS AND RESULTS: We herein present a 78-year-old female patient admitted with
      a giant, buccal mass that developed within the previous 2 years. Physical
      examination revealed a vegetative mass on the left buccal region without any
      cervical lymphadenopathy. Magnetic resonance imaging scan showed an 8- * 6-cm
      solid mass with cystic components in the left buccal region and thoracic computed
      tomography scanning revealed pulmonary metastasis. A successful surgery including
      lower lip splitting was performed, and the mass was totally excised with its
      surrounding capsule. Histopathologic examination revealed follicular variant of
      papillary carcinoma of the ectopic thyroid tissue. CONCLUSIONS: To our knowledge,
      our case is the first case of papillary carcinoma arising from ectopic thyroid
      tissue in the buccal region in the literature.

PMID- 22965923
TI  - Effects of aging on thyroarytenoid muscle regeneration.
AB  - OBJECTIVES/HYPOTHESIS: Regenerative properties of age-associated changes in the
      intrinsic laryngeal muscles following injury are unclear. The purpose of this
      study was to investigate the regenerative properties of the thyroarytenoid (TA)
      muscle in an aging rat model. The hypothesis was that following myotoxic injury,
      old animals would exhibit a decrease in mitotic activities of muscle satellite
      cells when compared with younger rats, suggesting reduced regenerative potential
      in the aging rat TA muscle. STUDY DESIGN: Animal group comparison. METHODS:
      Regeneration responses following injury to the TA muscle were examined in 18
      young adult, middle-aged, and old Fischer 344/Brown Norway rats. TA muscle fiber
      cross-sectional area (CSA), satellite cell mitosis (number/fiber), and
      regeneration index (CSA injured side/CSA noninjured side) were measured and
      compared across age groups. RESULTS: Young adult animals had a significantly
      higher regeneration index than the middle-aged and old groups. Within the lateral
      region of the TA muscle (LTA), the regeneration index was significantly higher in
      the young adult animals than in the middle-aged and old animals. The regeneration
      index of the medial TA was significantly higher than the LTA across all age
      groups. CONCLUSIONS: The regenerative capacity of the TA muscle is impaired with
      increasing age.

PMID- 22965925
TI  - Protein refolding using chemical refolding additives.
AB  - In laboratories and manufacturing settings, a rapid and inexpensive method for
      the preparation of a target protein is crucial for promoting resesrach in protein
      science and engineering. Inclusion-body-based protein production is a promising
      method because high yields are achieved in the upstream process, although the
      refolding of solubilized, unfolded proteins in downstream processes often leads
      to significantly lower yields. The most challenging problem is that the effective
      condition for refolding is protein dependent and is therefore difficult to select
      in a rational manner. Accordingly, considerable time and expense using trial-and
      error approaches are often needed to increase the final protein yield.
      Furthermore, for certain target proteins, finding suitable conditions to achieve
      an adequate yield cannot be obtained by existing methods. Therefore, to convert
      such a troublesome refolding process into a routine one, a wide array of methods
      based on novel technologies and materials have been developed. These methods
      select refolding conditions where productive refolding dominates over
      unproductive aggregation in competitive refolding reactions. This review focuses
      on synthetic refolding additives and describes the concepts underlying the
      development of reported chemical additives or chemical-additive-based methods
      that contribute to the emergence of a universal refolding method.

PMID- 22965926
TI  - Plasma treatment of electrospun PCL random nanofiber meshes (NFMs) for biological
      property improvement.
AB  - In this article, the plasma surface modification effects on the chemical,
      mechanical, and biological properties of electrospun poly (epsilon-caprolactone)
      (PCL) random nanofiber meshes (NFMs) were investigated by adjusting plasma
      chemistry, that is, using glow discharges of N(2) +H(2), NH(3) +O(2), and Ar+O(2)
      gas mixtures. The surface property changes of electrospun PCL NFMs after those
      plasma treatments were examined by water contact angle measurements and X-ray
      photoelectron spectroscopy. The experimental results showed that the plasma
      treatments introduced polar groups onto the surfaces and thus increased the
      surface hydrophilicity. From tensile test data, plasma treatment had limited
      effect on the mechanical properties of PCL random NFMs. The biological properties
      of the plasma-treated PCL NFMs were examined by cell proliferation assays using
      mouse osteoblast cells (MC3T3-E1). It was found that the plasma-treated PCL NFMs
      gave a higher proliferation rate and improved cell adhesion properties as
      compared with the untreated controls.

PMID- 22965927
TI  - Cleft palate in a multigenerational family with a microdeletion of 20p12.3
      involving BMP2.
AB  - Cleft palate (CP) is a frequent and recognizable birth defect attributed to a
      variety of etiologies including genetic abnormalities and environmental
      exposures. Bone morphogenetic proteins (BMPs) are involved in embryonic signaling
      important for a number of developmental processes including bone formation and
      palate morphogenesis. Recently, haploinsufficiency of BMP2 was associated with
      syndromic forms of CP. Here, we report on a multigenerational family with a
      history of CP as a result of a 2.3 Mb deletion of chromosome 20p12.3, including
      the BMP2 gene. In addition to a submucous CP, the proband's clinical phenotype
      included failure to thrive (FTT), global developmental delays (DD), and
      dysmorphic features. The affected father exhibited an overt CP, with a facial
      gestalt and minor dysmorphic features similar to the proband. The father was
      otherwise healthy with no history of FTT or DD, suggesting high penetrance, yet
      variable expressivity for haploinsufficiency of BMP2. The findings presented here
      provide further evidence for the role of BMP2 in syndromic forms of CP.

PMID- 22965928
TI  - Comparative rates of adverse events with different formulations of intravenous
      iron.
AB  - Oral iron replacement is the standard therapy in iron-deficiency anemia (IDA).
      However, 59% of patients have gastrointestinal toxicity. With impaired iron
      uptake from the gastrointestinal tract (in anemia of chronic disease (ACD) or
      after bariatric surgery), suboptimal responsiveness to exogenous erythropoietin
      (in chronic renal failure), in patients with cancer receiving chemotherapy, or
      when oral iron is poorly tolerated, IV iron therapy is the preferred mode of
      repletion. Although effective in increasing hemoglobin, the relative safety of
      the available IV iron preparations is not well documented. We examined the
      comparative safety of IV iron formulations used at hospitals associated with our
      institution. Among 619 unique patients who received IV iron over a 2-year period,
      we found 32 adverse events (AEs), ranging from urticaria to chest pain. There
      were no serious AEs or anaphylactic-type reactions. In a multivariate model,
      there was no difference in AE rates between low-molecular-weight iron dextran
      (LMWD) and ferric gluconate; however, iron sucrose had significantly higher odds
      ratio of AEs (OR = 5.7; 95% CI = 1.6-21.3). Our data suggest that AE rates with
      IV iron are acceptable. More widespread use of LMWD, in particular, which can be
      given safely as a total dose infusion (TDI), should be considered.

PMID- 22965929
TI  - Enantioselective synthesis of beta,gamma-unsaturated alpha-fluoroesters catalyzed
      by N-heterocyclic carbenes.

PMID- 22965930
TI  - Computed tomography has low yield in the evaluation of idiopathic unilateral true
      vocal fold paresis.
AB  - OBJECTIVE/HYPOTHESIS: To determine the clinical yield of neck and chest computed
      tomography in the initial assessment of patients with idiopathic unilateral true
      vocal fold paresis. STUDY DESIGN: Retrospective chart review. METHODS: A
      retrospective chart review of consecutive adult patients with idiopathic
      unilateral true vocal fold paresis diagnosed by stroboscopy in a tertiary-care
      voice center from 2003 to 2010. RESULTS: There were 176 patients with unilateral
      vocal fold paresis of which 81 subjects had idiopathic unilateral true vocal fold
      paresis. Of these, 60 patients (74.1%) had a computed tomography workup. Fifty
      nine patients (98.3%) had a normal computed tomography while one patient had a
      single mediastinal lymph node that was PET-CT negative. This demonstrates an
      initial 1.7% yield and ultimate 0% yield of the computed tomography workup.
      CONCLUSION: Our results suggest that computed tomography workup has a low yield
      for occult neck and mediastinal pathology in patients with idiopathic unilateral
      true vocal fold paresis. Chest and neck computed tomography may not be clinically
      beneficial provided the patient has good otolaryngologic and medical follow-up.

PMID- 22965931
TI  - Identification of CUX1 as the recurrent chromosomal band 7q22 target gene in
      human uterine leiomyoma.
AB  - Uterine leiomyomas are benign solid tumors of mesenchymal origin which occur with
      an estimated incidence of up to 77% of all women of reproductive age. The
      majority of these tumors remains symptomless, but in about a quarter of cases
      they cause leiomyoma-associated symptoms including chronic pelvic pain,
      menorrhagia-induced anemia, and impaired fertility. As a consequence, they are
      the most common indication for pre-menopausal hysterectomy in the USA and Japan
      and annually translate into a multibillion dollar healthcare problem.
      Approximately 40% of these neoplasms present with recurring structural
      cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24),
      and anomalies affecting 6p21 and/or 10q22. Using positional cloning strategies,
      we and others previously identified HMGA1, HMGA2, RAD51L1, MORF, and, more
      recently, NCOA1 as primary target (fusion) genes associated with tumor initiation
      in four of these distinct cytogenetic subgroups. Despite the fact that the
      del(7)(q22) subgroup is the largest among leiomyomas, and was first described
      more than twenty years ago, the 7q22 leiomyoma target gene still awaits
      unequivocal identification. We here describe a positional cloning effort from two
      independent uterine leiomyomas, containing respectively a pericentric and a
      paracentric chromosomal inversion, both affecting band 7q22. We found that both
      chromosomal inversions target the cut-like homeobox 1 (CUX1) gene on chromosomal
      band 7q22.1 in a way which is functionally equivalent to the more frequently
      observed del(7q) cases, and which is compatible with a mono-allelic knock-out
      scenario, similar as was previously described for the cytogenetic subgroup
      showing chromosome 14q involvement.

PMID- 22965933
TI  - Monitoring and control of microbioreactors: an expert opinion on development
      needs.
AB  - This perspective article is based on an expert panel review on microbioreactor
      applications in biochemical and biomedical engineering that was organized by the
      M3C (measurement, monitoring, modelling and control) Working Group of the
      European Section of Biochemical Engineering Science (ESBES) in the European
      Federation of Biotechnology (EFB). The aim of the panel was to provide an updated
      view on the present status of the subject and to identify critical needs and
      issues for furthering the successful development of microbioreactor monitoring
      and control. This will benefit future bioprocess development and in vitro
      toxicity testing. The article concludes with a set of recommendations for
      extended use and further development of microbioreactors.

PMID- 22965932
TI  - Effects of composition and setting environment on mechanical properties of a
      composite bone filler.
AB  - Large bone defects can be difficult to treat, even with autografts. Bone graft
      substitutes, such as calcium sulfate (CS), calcium phosphate cements, and
      hydroxyapatite, are receiving significant attention because of their
      biocompatibility and potential for incorporation of therapeutic agents. To create
      a bone filler capable of treating irregularly shaped, often infected, bony
      defects, microspheres and a plasticizer were added to CS, resulting in a moldable
      composite capable of being loaded with biomolecules. Different compositions and
      setting environments, such as immersion in saline, a humidified incubator, or
      room temperature air, were investigated to determine their effects on mechanical
      strength and degradation rate of the composites. Addition of any other components
      to the CS, such as plasticizers or microspheres composed of biopolymers (gelatin,
      hyaluronan [HY], cellulose acetate phthalate, and carboxymethylcellulose),
      increased its functionality but reduced mechanical strength. The compressive
      modulus and strength of the composite fillers ranged from 10 to 350 MPa and 5 to
      20 MPa, respectively, depending on the composition. This moldable bone filler
      degraded in 18-20 days when placed in solution and was able to set in harsh
      environments given a composition that did not retain too much water. By combining
      a plasticizing agent, such as HY with CS, a composite material has been developed
      that is moldable, sets in situ, and maintains its mechanical stability. With
      these desirable properties for a bone graft substitute and the potential to be
      loaded with bioactive drugs, this composite material merits further investigation
      for the future treatment of bony defects.

PMID- 22965934
TI  - Talking about suicide: confidentiality and anonymity in qualitative research.
AB  - While it is acknowledged that there is a need for more qualitative research on
      suicide, it is also clear that the ethics of undertaking such research need to be
      addressed. This article uses the case study of the authors' experience of gaining
      ethics approval for a research project that asks people what it is like to feel
      suicidal to (a) analyse the limits of confidentiality and anonymity and (b)
      consider the ways in which the process of ethics review can shape and constrain
      suicide research. This leads to a discussion of the ways in which ethics
      committees assess and monitor qualitative research more generally and some
      preliminary suggestions for how this might be improved.

PMID- 22965935
TI  - Interstitial deletion of 11q-implicating the KIRREL3 gene in the neurocognitive
      delay associated with Jacobsen syndrome.
AB  - Jacobsen syndrome (JS) is a rare contiguous gene disorder characterized by a
      deletion within the distal part of the long arm of chromosome 11 ranging in size
      from 7 to 20 Mb. The clinical findings include characteristic dysmorphic
      features, growth and psychomotor delays and developmental anomalies involving the
      brain, eyes, heart, kidneys, immune, hematologic, endocrine, and gastrointestinal
      systems. The majority of cases are due to a terminal deletion of 11q; however
      interstitial deletions have also been reported. We report on a child with
      clinical manifestations consistent with JS who had a 2.899 Mb interstitial
      deletion at 11q24.2-q24.3 which is the smallest interstitial deletion reported so
      far to our knowledge. This deletion includes the KIRREL3 gene, and given our
      patient's history of neurocognitive delay and autism spectrum disorder, it raises
      the possibility that this gene is a candidate for the social and expressive
      language delay observed in our patient.

PMID- 22965936
TI  - Combining group-based exposure therapy with prolonged exposure to treat U.S.
      Vietnam veterans with PTSD: a case study.
AB  - Group-based exposure therapy (GBET) of 16-week duration was developed to treat
      combat-related posttraumatic stress disorder (PTSD) and decreased PTSD symptoms
      in 3 noncontrolled open trials with low attrition (0%-5%). Group-based exposure
      therapy has not produced as much PTSD symptom reduction as Prolonged Exposure
      (PE) within a U.S. Veterans Affairs PTSD treatment program, although PE had more
      dropouts (20%). This pilot study was of a model that combined key elements of
      GBET with components of PE in an effort to increase the effectiveness of a group
      based treatment while reducing its length and maintaining low attrition. Twice
      per week, 8 Vietnam combat veterans with PTSD were treated for 12 weeks, with an
      intervention that included 2 within-group war trauma presentations per
      participant, 6 PE style individual imaginal exposure (IE) sessions per
      participant, daily listening to recorded IE sessions, and daily in vivo exposure
      exercises. All completed treatment and showed Significant reductions on all
      measures of PTSD with large effect sizes; 7 participants no longer met PTSD
      criteria on treating clinician administered interviews and a self-report measure
      at posttreatment. Significant reductions in depression with large effect sizes
      and moderate reductions in PTSD-related cognitions were also found. Most gains
      were maintained 6 months posttreatment.

PMID- 22965937
TI  - An autonomously self-assembling dendritic DNA nanostructure for target DNA
      detection.
AB  - There is a growing need for sensitive and reliable nucleic acid detection methods
      that are convenient and inexpensive. Responsive and programmable DNA
      nanostructures have shown great promise as chemical detection systems. Here, we
      describe a DNA detection system employing the triggered self-assembly of a novel
      DNA dendritic nanostructure. The detection protocol is executed autonomously
      without external intervention. Detection begins when a specific, single-stranded
      target DNA strand (T) triggers a hybridization chain reaction (HCR) between two,
      distinct DNA hairpins (alpha and beta). Each hairpin opens and hybridizes up to
      two copies of the other. In the absence of T, alpha and beta are stable and
      remain in their poised, closed-hairpin form. In the presence of T, alpha hairpins
      are opened by toe-hold mediated strand-displacement, each of which then opens and
      hybridizes two beta hairpins. Likewise, each opened beta hairpin can open and
      hybridize two alpha hairpins. Hence, each layer of the growing dendritic
      nanostructure can in principle accommodate an exponentially increasing number of
      cognate molecules, generating a high molecular weight nanostructure. This HCR
      system has minimal sequence constraints, allowing reconfiguration for the
      detection of arbitrary target sequences. Here, we demonstrate detection of unique
      sequence identifiers of HIV and Chlamydia pathogens.

PMID- 22965938
TI  - Evaluation of single-cell force spectroscopy and fluorescence microscopy to
      determine cell interactions with femtosecond-laser microstructured titanium
      surfaces.
AB  - One goal in biomaterials research is to limit the formation of connective tissue
      around the implant. Antiwetting surfaces are known to reduce ability of cells to
      adhere. Such surfaces can be achieved by special surface structures (lotus
      effect). Aim of the study was to investigate the feasibility for creating
      antiwetting surface structures on titanium and to characterize their effect on
      initial cell adhesion and proliferation. Titanium microstructures were generated
      using femtosecond- (fs-) laser pulses. Murine fibroblasts served as a model for
      connective tissue cells. Quantitative investigation of initial cell adhesion was
      performed using atomic force microscopy. Fluorescence microscopy was used for the
      characterization of cell-adhesion pattern, cell morphology, and proliferation.
      Water contact angle (WCA) measurements evinced antiwetting properties of laser
      structured surfaces. However, the WCA was decreased in serum-containing medium.
      Initial cell adhesion to microstructured titanium was significantly promoted when
      compared with polished titanium. Microstructures did not influence cell
      proliferation on titanium surfaces. However, on titanium microstructures, cells
      showed a flattened morphology, and the cell orientation was biased according to
      the surface topography. In conclusion, antiwetting properties of surfaces were
      absent in the presence of serum and did not hinder adhesion and proliferation of
      NIH 3T3 fibroblasts.

PMID- 22965939
TI  - Treatment with sunitinib for patients with progressive metastatic
      pheochromocytomas and sympathetic paragangliomas.
AB  - CONTEXT: Patients with progressive metastatic pheochromocytomas (PHEOs) or
      sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic
      therapies are limited. OBJECTIVES: The primary end point was progression-free
      survival determined by RECIST 1.1 criteria or positron emission tomography with
      [(18)F]fluorodeoxyglucose/computed tomography ([(18)F]FDG-PET/CT), in the absence
      of measurable soft tissue targets. Secondary endpoints were tumor response
      according to RECIST criteria version 1.1 or FDG uptake, blood pressure control,
      and safety. DESIGN: We conducted a retrospective review of medical records of
      patients with metastatic PHEO/SPGL treated with sunitinib from December 2007
      through December 2011. An intention-to-treat analysis was performed. PATIENTS AND
      SETTING: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the
      Institut Gustave-Roussy and MD Anderson Cancer Center. INTERVENTIONS: Patients
      treated with sunitinib. RESULTS: According to RECIST 1.1, eight patients
      experienced clinical benefit; three experienced partial response, and five had
      stable disease, including four with predominant skeletal metastases that showed a
      30% or greater reduction in glucose uptake on [(18)F]FDG-PET/CT. Of 14 patients
      who had hypertension, six became normotensive and two discontinued
      antihypertensives. One patient treated with sunitinib and rapamycin experienced a
      durable benefit beyond 36 months. The median overall survival from the time
      sunitinib was initiated was 26.7 months with a progression-free survival of 4.1
      months (95% confidence interval = 1.4-11.0). Most patients who experienced a
      clinical benefit were carriers of SDHB mutations. CONCLUSION: Sunitinib is
      associated with tumor size reduction, decreased [(18)F]FDG-PET/CT uptake, disease
      stabilization, and hypertension improvement in some patients with progressive
      metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed
      to determine the true benefits of sunitinib.

PMID- 22965940
TI  - Let-7a down-regulation plays a role in thyroid neoplasias of follicular histotype
      affecting cell adhesion and migration through its ability to target the FXYD5
      (Dysadherin) gene.
AB  - CONTEXT: Thyroid neoplasias of the follicular histotype include the benign
      follicular adenomas and the malignant follicular carcinomas. Although several
      genetic lesions have already been described in human thyroid follicular
      neoplasias, the mechanisms underlying their development are still far from being
      completely elucidated. MicroRNAs (miRs or miRNAs) have recently emerged as
      important regulators of gene expression, also playing a key role in the process
      of carcinogenesis. OBJECTIVE: The aim of our work has been to identify the miRNAs
      differentially expressed in human thyroid follicular neoplasias and define their
      role in thyroid carcinogenesis. DESIGN: The miRNA expression profile of 10 human
      thyroid follicular adenomas was compared to that of 10 normal thyroid tissues.
      RESULTS: The miRNA expression profiles revealed the down-regulation of let-7a in
      thyroid follicular adenomas compared to normal thyroid. Then, quantitative RT-PCR
      analyses validated the microarray data and showed a significantly higher decrease
      in let-7a expression in follicular carcinomas. Enforced let-7a expression in the
      follicular thyroid carcinoma cell line WRO induces an epithelial-like phenotype,
      increases cell adhesion, and decreases cell migration. Conversely, silencing of
      let-7a in the normal rat thyroid cell line PC Cl 3 has opposite effects. We
      identified dysadherin (FXYD5), a cell membrane glycoprotein, correlated with
      tumor progression and invasiveness, as a target of let-7a. Consistently, an
      inverse correlation between dysadherin and let-7a expression levels was found in
      human thyroid follicular adenomas and carcinomas. CONCLUSIONS: These results
      suggest a role of let-7a down-regulation in the development of thyroid neoplasias
      of the follicular histotype, likely regulating dysadherin protein expression
      levels.

PMID- 22965942
TI  - Pharmacological blocking of the osteoclastic biocorrosion of surgical stainless
      steel in vitro.
AB  - In vitro studies suggest that human osteoclasts (OC) are able to corrode surgical
      stainless steel 316L (SS). The aim of this study was to investigate whether
      osteoclastic biocorrosion can be blocked pharmacologically. Human OCs were
      generated in vitro from peripheral blood monocytic cells (PBMCs) in the presence
      of OC differentiation cytokines. The osteoclastic viability, differentiation, and
      resorptive function (on both bone and SS) were assessed using standard
      colorimetric cell viability assay 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium, inner salt (MTS),
      fluorescence microscopy, tartrate-resistant acid phosphatase expression (flow
      cytometry), and scanning electron microscopy. OCs cultured on SS were exposed to
      nontoxic concentrations of bafilomycin A1, amiloride hydrochloride, or zoledronic
      acid. The extent of biocorrosion was quantified using atomic emission
      spectrometry (to measure the concentration of metal ions released into the
      supernatant) and scanning electron microscopy. PBMCs differentiated into mature
      and functional OC in the presence of all the drugs used. Osteoclastic resorption
      of SS was noted with differences in the resorption pattern for all drug
      treatments. Under the drug treatments, single areas of osteoclastic resorption
      were larger in size but less abundant when compared with positive controls. None
      of the drugs used were able to inhibit osteoclastic biocorrosion of SS.

PMID- 22965943
TI  - Mechanical left ventricular support using a 50 cc 8 Fr fibre-optic intra-aortic
      balloon technology: a case report.
AB  - INTRODUCTION: More than four decades have passed since the first clinical use of
      an (IABP) to improve the clinical scenario for patients with chronic left
      ventricular failure. The original IAB catheter size was 15 French (Fr), requiring
      an open surgical insertion and removal. This therapy has now become the most
      widely used mechanical device for failure of the left ventricle. The introduction
      of an 8 Fr fibre-optic IAB catheter with a 50 cc diastolic blood volume
      displacement has further increased the potential clinical impact of this
      technology. This new catheter can be used for all patients over 162 cm in height,
      allowing a broader spectrum of patients to benefit from increased diastolic blood
      volume displacement and fibre-optic pressure monitoring. The catheter has been
      designed on an 8 Fr shaft platform, potentially reducing the incidence of
      vascular complications. We present our case report on the world's first implant
      of this 50cc 8 Fr IAB catheter. CASE REPORT: Cardiac investigations on a 53-year
      old man showed the patient to have ischaemic dilated cardiomyopathy with a left
      ventricular ejection fraction (LVEF) of 25%. An 8 Fr 50cc Sensation PlusTM IAB
      catheter was inserted pre-operatively, prior to coronary artery bypass grafting.
      RESULTS: The world's first insertion of this 8 Fr 50 cc IAB catheter was a
      complete success, with no complications. The patient's pre-, peri- and post
      operative courses were as we expected and event free, underpinned by IABP
      support. CONCLUSION: This new 50 cc, 8 Fr IAB expands the patient group that can
      benefit from greater diastolic blood volume delivery, improved distal perfusion,
      more accurate monitoring, subsequent better beat-per-beat support and, finally,
      the reduced complication rates associated with an 8 Fr shaft.

PMID- 22965941
TI  - Clinical review: Genome-wide association studies of skeletal phenotypes: what we
      have learned and where we are headed.
AB  - CONTEXT: The primary goals of genome-wide association studies (GWAS) are to
      discover new molecular and biological pathways involved in the regulation of bone
      metabolism that can be leveraged for drug development. In addition, the
      identified genetic determinants may be used to enhance current risk factor
      profiles. EVIDENCE ACQUISITION: There have been more than 40 published GWAS on
      skeletal phenotypes, predominantly focused on dual-energy x-ray absorptiometry
      derived bone mineral density (BMD) of the hip and spine. EVIDENCE SYNTHESIS:
      Sixty-six BMD loci have been replicated across all the published GWAS, confirming
      the highly polygenic nature of BMD variation. Only seven of the 66 previously
      reported genes (LRP5, SOST, ESR1, TNFRSF11B, TNFRSF11A, TNFSF11, PTH) from
      candidate gene association studies have been confirmed by GWAS. Among 59 novel
      BMD GWAS loci that have not been reported by previous candidate gene association
      studies, some have been shown to be involved in key biological pathways involving
      the skeleton, particularly Wnt signaling (AXIN1, LRP5, CTNNB1, DKK1, FOXC2,
      HOXC6, LRP4, MEF2C, PTHLH, RSPO3, SFRP4, TGFBR3, WLS, WNT3, WNT4, WNT5B, WNT16),
      bone development: ossification (CLCN7, CSF1, MEF2C, MEPE, PKDCC, PTHLH, RUNX2,
      SOX6, SOX9, SPP1, SP7), mesenchymal-stem-cell differentiation (FAM3C, MEF2C,
      RUNX2, SOX4, SOX9, SP7), osteoclast differentiation (JAG1, RUNX2), and TGF
      signaling (FOXL1, SPTBN1, TGFBR3). There are still 30 BMD GWAS loci without prior
      molecular or biological evidence of their involvement in skeletal phenotypes.
      Other skeletal phenotypes that either have been or are being studied include hip
      geometry, bone ultrasound, quantitative computed tomography, high-resolution
      peripheral quantitative computed tomography, biochemical markers, and fractures
      such as vertebral, nonvertebral, hip, and forearm. CONCLUSIONS: Although several
      challenges lie ahead as GWAS moves into the next generation, there are prospects
      of new discoveries in skeletal biology. This review integrates findings from
      previous GWAS and provides a roadmap for future directions building on current
      GWAS successes.

PMID- 22965944
TI  - Fiber-optic intra-aortic balloon therapy and its role within cardiac surgery.
AB  - INTRODUCTION: The patient population has changed and the cardiothoracic team are
      now operating on patients with more co-morbidity. One of the significant aspects
      of this increased co-morbidity, which affects both short- and long-term outcomes,
      is compromised left ventricular function. Intra-aortic balloon pump (IABP)
      technology offers these patients and the cardiac team an easily accessible, cost
      effective, mechanical assist device. Arterial pressure monitoring for IABP
      therapy: Fluid-filled transducers used to measure the aortic waveform can be
      unreliable and inconsistent. Fiber-optic manometers located in the very tip of
      the IAB catheters provide accurate and fast, high quality measurements. This, in
      turn, presents the opportunity for the hardware and algorithm to measure key
      markers on the arterial waveform and optimise left ventricular support. It also
      provides the potential for automatic in vivo calibration, further increasing the
      accuracy and quality of the IAB support. The effect of fiber-optic IABP therapy
      on clinical management: A dual centre prospective audit comparing fluid-filled
      versus fiber-optic arterial pressure monitoring showed a 96% reduction in IAB
      related perfusion on-site call-outs (17 vs. 1, respectively) and a 94% reduction
      in sub-optimal timing (55/98 vs. 2/94, respectively). CONCLUSION: The improved
      timing algorithms utilise the pressure information received 50 msecs faster than
      with fluid-filled transducers, measuring key markers on the pressure waveform and
      adjusting inflation and deflation accurately on a beat per beat basis. Fiber
      optic IAB technology and, specifically, these improved algorithms provide better
      beat per beat mechanical support. Given our evolving patient population, this
      technology will not only play an increased role, but will have a significant
      impact on cardiac surgery.

PMID- 22965945
TI  - Self-interest without selfishness: the hedonic benefit of imposed self-interest.
AB  - Despite commonsense appeal, the link between self-interest and happiness remains
      elusive. One reason why individuals may not feel satisfied with self-interest is
      that they feel uneasy about sacrificing the needs of others for their own gain.
      We propose that externally imposing self-interest allows individuals to enjoy
      self-benefiting outcomes that are untainted by self-reproach for failing to help
      others. Study 1 demonstrated that an imposed self-interested option (a reward)
      leads to greater happiness than does choosing between a self-interested option
      and a prosocial option (a charity donation). Study 2 demonstrated that this
      effect is not driven by choice in general; rather, it is the specific trade-off
      between benefiting the self and benefiting others that inhibits happiness gained
      from self-interest. We theorize that the agency inherent in choice reduces the
      hedonic value of self-interest. Results of Study 3 find support for this
      mechanism.

PMID- 22965946
TI  - Dynamics of the lakes in the middle and lower reaches of the Yangtze River basin,
      China, since late nineteenth century.
AB  - The middle and lower reaches of the Yangtze River basin have the most
      representative and largest concentration of freshwater lakes in China. However,
      the size and number of these lakes have changed considerably over the past
      century due to the natural and anthropogenic impact. The lakes, larger than 10
      km(2) in size, were chosen from relief maps and remotely sensed images in 1875,
      1950, 1970, 1990, 2000, and 2008 to study the dynamics of lakes in the middle and
      lower reaches of the Yangtze River basin and to examine the causes and
      consequences of these changes. Results indicated that there was a dramatic
      reduction in lake areas, which decreased by 7,841.2 km(2) (42.64 %) during the
      study period (1875-2008), and the number of lakes in this region changed
      moderately. Meanwhile, a large number of lakes in the middle and lower reaches of
      the Yangtze River basin were directly converted into paddy fields, ponds,
      building lands, or other land-use types over the study period. Therefore, all
      kinds of lake reclamation should be identified as the major driving factors for
      the loss of lake in this region. Furthermore, flooding, soil erosion, and
      sedimentation were also the main factors which triggered lake changes in
      different periods. Some wetland conservation and restoration projects have been
      implemented since the 1970s, but they have not reversed the lake degradation.
      These findings were of great importance to managers involved in making policy for
      the conservation of lake ecosystems and the utilization of lake resources.

PMID- 22965947
TI  - Effects of land use types on surface water quality across an anthropogenic
      disturbance gradient in the upper reach of the Hun River, Northeast China.
AB  - Surface water quality is vulnerable to pollution due to human activities. The
      upper reach of the Hun River is an important water source that supplies 52 % of
      the storage capacity of the Dahuofang Reservoir, the largest reservoir for
      drinking water in Northeast China, which is suffering from various human-induced
      changes in land use, including deforestation, reclamation/farming, urbanization
      and mine exploitation. To investigate the impacts of land use types on surface
      water quality across an anthropogenic disturbance gradient at a local scale, 11
      physicochemical parameters (pH, dissolved oxygen [DO], turbidity, oxygen redox
      potential, conductivity, biochemical oxygen demand [BOD5], chemical oxygen demand
      [COD], total nitrogen [TN], total phosphorus [TP], NO(3)(-)N, and NH(4)(+)-N) of
      water from 12 sampling sites along the upper reach of the Hun River were
      monitored monthly during 2009-2010. The sampling sites were classified into four
      groups (natural, near-natural, more disturbed, and seriously disturbed). The
      water quality exhibited distinct spatial and temporal characteristics;
      conductivity, TN, and NO(3)(-)-N were identified as key parameters indicating the
      water quality variance. The forest and farmland cover types played significant
      roles in determining the surface water quality during the low-flow, high-flow,
      and mean-flow periods based on the results of a stepwise linear regression. These
      results may provide incentive for the local government to consider sustainable
      land use practices for water conservation.

PMID- 22965948
TI  - Sensitivity of isolated eggs of pond snails: a new method for toxicity assays and
      risk assessment.
AB  - The concentration of heavy metals in the environment is normally low. We here
      address whether using the development of isolated pond snail Radix auricularia
      eggs would provide a more sensitive endpoint and whether the gelatinous matrix of
      the egg mass surrounding the eggs indeed protects the snail embryos. In the
      present study, artificial removal of the gelatinous matrix of egg masses greatly
      increased the sensitivity of developing eggs to a heavy metal (cadmium). The
      sensitivity of isolated eggs to cadmium was determined using several convenient
      endpoints, including mortality, hatching rate, and heart rate, with an acute
      toxicity test and a subchronic test. In the acute toxicity test, a 96-h LC(50)
      value of 58.26 MUg/L cadmium was determined. In the subchronic toxicity test,
      sublethal effects in terms of a significant reduction in hatching rate could be
      found in the 25-MUg/L treatment, and a significant decrease of heart rate was
      observed in both treatments (5 and 25 MUg/L). The high sensitivity of isolated
      eggs indicates that such tests can be efficient for toxicity assays and risk
      assessment, although one needs to keep in mind that the ecologically relevant
      measure of toxicity will be how eggs are affected when they are still inside the
      egg mass.

PMID- 22965950
TI  - Long-term results of carotid artery stenting in patients 80 years and older.
AB  - INTRODUCTION: We report our experience about carotid artery stenting (CAS) in
      patients 80 years and older. MATERIALS AND METHODS: Out of 582 patients who
      underwent CAS at our institution from January 1999 to June 2010, 102 patients
      (group A) were 80 years or older. The clinical data of these patients were
      retrospectively reviewed, outcomes analyzed, and compared with those of younger
      patients who underwent CAS during the same period (group B). RESULTS: Outcomes of
      group B were similar to those of group A, both at 30 days and at long term. Male
      gender, symptoms, and not using an embolic protection device were related to long
      term complications in both groups. Occurrence of bradycardia/asystole during CAS
      was a risk factor for long-term myocardial infarction for group A only.
      CONCLUSIONS: CAS can be safely performed in patients 80 years or older, with
      results that compare favorably to those of younger patients.

PMID- 22965951
TI  - Diesel engine exhaust classified as a human lung carcinogen. How will this affect
      occupational exposures?

PMID- 22965949
TI  - Beta-glucan: an ideal immunostimulant in aquaculture (a review).
AB  - The major hindrance in the development and sustainability of aquaculture industry
      is the occurrence of various diseases in the farming systems. Today, preventive
      and management measures are central concern to overcome such outbreak of
      diseases. Immunostimulants are considered as an effective tool for enhancing
      immune status of cultured organisms. Among different immunostimulants used in
      aquaculture practices, beta-glucan is one of the promising immunostimulant, which
      is a homopolysaccharide of glucose molecule linked by the glycoside bond. It
      forms the major constituents of cell wall of some plants, fungi, bacteria,
      mushroom, yeast, and seaweeds. Major attention on beta-glucan was captivated with
      the gain in knowledge on its receptors and the mechanism of action. The receptor
      present inside the animal body recognizes and binds to beta-glucan, which in turn
      renders the animal with high resistance and enhanced immune response. This review
      highlights beta-glucan as an immunostimulant, its effective dosages, and route of
      administration and furthermore provides an outline on role of beta-glucan in
      enhancing growth, survival, and protection against infectious pathogens
      pertaining to fishes and shellfishes. Study also summarizes the effect of beta
      glucan on its receptors, recognition of proteins, immune-related enzymes, immune
      related gene expression and their mechanisms of action.

PMID- 22965952
TI  - Targeting mutant p53 in human tumors.

PMID- 22965953
TI  - Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246
      in refractory hematologic malignancies and prostate cancer.
AB  - PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional
      activity of unfolded wild-type or mutant p53. The main aims of this first-in
      human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting
      toxicities (DLTs), and pharmacokinetics (PK) of APR-246. PATIENTS AND METHODS:
      APR-246 was administered as a 2-hour intravenous infusion once per day for 4
      consecutive days in 22 patients with hematologic malignancies and prostate
      cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the
      most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90
      mg/kg. RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the
      most common adverse effects were fatigue, dizziness, headache, and confusion.
      DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory
      disturbances (n = 2). PK showed little interindividual variation and were neither
      dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed
      cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in
      several patients. Global gene expression analysis revealed changes in genes
      regulating proliferation and cell death. One patient with AML who had a p53 core
      domain mutation showed a reduction of blast percentage from 46% to 26% in the
      bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site
      mutation showed a minor response. CONCLUSION: We conclude that APR-246 is safe at
      predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile,
      and can induce p53-dependent biologic effects in tumor cells in vivo.

PMID- 22965954
TI  - Hepatocellular carcinoma as unusual cause for paraplegia.

PMID- 22965956
TI  - Clarifying the American Society of Clinical Oncology practice guideline for
      chemotherapy dosing for obese adults.

PMID- 22965955
TI  - Comparative analysis of different approaches to measure treatment response in
      acute myeloid leukemia.
AB  - PURPOSE: In acute myeloid leukemia (AML), initial treatment response by
      morphologic analysis of bone marrow predicts long-term outcome. Response can now
      be assessed by minimal residual disease (MRD) monitoring with flow cytometry or
      polymerase chain reaction (PCR). We determined the relation among the results of
      these approaches and their prognostic value. PATIENTS AND METHODS: In the
      multicenter AML02 study, follow-up bone marrow samples from 203 children and
      adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514),
      morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508).
      Results were correlated with treatment outcome. RESULTS: Among 1,215 samples with
      less than 5% leukemic myeloblasts by morphology, 100 (8.2%) were MRD positive (>=
      0.1%) by flow cytometry, whereas 96 (57.5%) of the 167 samples with >= 5% blasts
      were MRD negative. Virtually all (308 of 311; 99.0%) MRD-negative samples by PCR
      were also MRD negative by flow cytometry. However, only 19 (9.6%) of the 197 PCR
      positive samples were flow cytometry positive, with analyses of AML1-ETO and
      CBFbeta-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive
      samples had detectable MRD by flow cytometry. MRD by flow cytometry after
      induction 1 or 2 predicted lower event-free survival and higher relapse rate (P <
      .001) and was an independent prognostic factor in a multivariable analysis;
      prediction was not improved by morphologic information or molecular findings.
      CONCLUSION: In childhood AML, morphologic assessment of treatment response has
      limited value if MRD is measured by flow cytometry. MLL fusion transcripts can
      provide prognostic information in some patients, whereas monitoring of AML1-ETO
      and CBFbeta-MYH11 transcripts is largely uninformative.

PMID- 22965957
TI  - Multiple myeloma with prostate involvement: a case report.

PMID- 22965958
TI  - Tale of two lymphomas: peripheral T-cell lymphoma after allogeneic stem-cell
      transplantation for marginal zone lymphoma.

PMID- 22965959
TI  - Janus reveals another face: the biologic rationale for targeting Janus kinase 2
      in lymphoma.

PMID- 22965960
TI  - Randomized, double-blind, placebo-controlled study to assess the efficacy and
      toxicity of subcutaneous ketamine in the management of cancer pain.
AB  - PURPOSE: The anesthetic ketamine is widely used for pain related to cancer, but
      the evidence to support its use in this setting is weak. This study aimed to
      determine whether ketamine is more effective than placebo when used in
      conjunction with opioids and standard adjuvant therapy in the management of
      chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if
      it provided clinically relevant improvement in pain with limited breakthrough
      analgesia and acceptable toxicity. PATIENTS AND METHODS: In this multisite, dose
      escalation, double-blind, randomized, placebo-controlled phase III trial,
      ketamine or placebo was delivered subcutaneously over 3 to 5 days. RESULTS: In
      all, 185 participants were included in the primary analysis. There was no
      significant difference between the proportion of positive outcomes (0.04; 95% CI,
      -0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27%
      [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a
      predictor of response. There was almost twice the incidence of adverse events
      worse than baseline in the ketamine group after day 1 (incidence rate ratio,
      1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving
      ketamine were more likely to experience a more severe grade of adverse event per
      day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients
      needed to treat for one additional patient to have a positive outcome from
      ketamine was 25 (95% CI, six to infinity). The number needed to harm, because of
      toxicity-related withdrawal, was six (95% CI, four to 13). CONCLUSION: Ketamine
      does not have net clinical benefit when used as an adjunct to opioids and
      standard coanalgesics in cancer pain.

PMID- 22965962
TI  - Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in
      patients with advanced or metastatic non-small-cell lung cancer: a randomized,
      controlled phase III trial.
AB  - PURPOSE: To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant
      human fusion protein targeting the vascular endothelial growth factor (VEGF)
      pathway, with or without docetaxel in platinum-pretreated patients with advanced
      or metastatic nonsquamous non-small-cell lung cancer. PATIENTS AND METHODS: In
      this international, double-blind, placebo-controlled phase III trial, 913
      patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n =
      456) or IV placebo (n = 457), both administered every 3 weeks and in combination
      with docetaxel 75 mg/m(2). The primary end point was overall survival (OS). Other
      efficacy outcomes, safety, and immunogenicity were also assessed. RESULTS:
      Patient characteristics were balanced between arms; 12.3% of patients had
      received prior bevacizumab. (Ziv-)Aflibercept did not improve OS (hazard ratio
      [HR], 1.01; 95% CI, 0.87 to 1.17; stratified log-rank P = .90). The median OS was
      10.1 months (95% CI, 9.2 to 11.6 months) for (ziv-)aflibercept and 10.4 months
      (95% CI, 9.2 to 11.9 months) for placebo. In exploratory analyses, median
      progression-free survival was 5.2 months (95% CI, 4.4 to 5.6 months) for (ziv
      )aflibercept versus 4.1 months (95% CI, 3.5 to 4.3 months) for placebo (HR, 0.82;
      95% CI, 0.72 to 0.94; P = .0035); overall response rate was 23.3% of evaluable
      patients (95% CI, 19.1% to 27.4%) in the (ziv-)aflibercept arm versus 8.9% (95%
      CI, 6.1% to 11.6%; P < .001) in the placebo arm. Grade >= 3 adverse events
      occurring more frequently in the (ziv-)aflibercept arm versus the placebo arm
      were neutropenia (28.0% v 21.1%, respectively), fatigue (11.1% v 4.2%,
      respectively), stomatitis (8.8% v 0.7%, respectively), and hypertension (7.3% v
      0.9%, respectively). CONCLUSION: The addition of (ziv-)aflibercept to standard
      docetaxel therapy did not improve OS. In exploratory analyses, secondary efficacy
      end points did seem to be improved in the (ziv-)aflibercept arm. The study
      regimen was associated with increased toxicities, consistent with known anti-VEGF
      and chemotherapy-induced events.

PMID- 22965961
TI  - Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment
      for patients with advanced colorectal cancer: a double-blind, randomized phase
      III study (HORIZON III).
AB  - PURPOSE: To compare the efficacy of cediranib (a vascular endothelial growth
      factor receptor tyrosine kinase inhibitor [VEGFR TKI]) with that of bevacizumab
      (anti-VEGF-A monoclonal antibody) in combination with chemotherapy as first-line
      treatment for advanced metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:
      HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients
      With Untreated Metastatic Colorectal Cancer] had an adaptive phase II/III design.
      Patients randomly assigned 1:1:1 received mFOLFOX6 [oxaliplatin 85 mg/m(2) and
      leucovorin 400 mg/m(2) intravenously followed by fluorouracil 400 mg/m(2)
      intravenously on day 1 and then continuous infusion of 2,400 mg/m(2) over the
      next 46 hours every 2 weeks] with cediranib (20 or 30 mg per day) or bevacizumab
      (5 mg/kg every 14 days). An independent end-of-phase II analysis concluded that
      mFOLFOX6/cediranib 20 mg met predefined criteria for continuation; subsequent
      patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab (randomly
      assigned 1:1). The primary objective was to compare progression-free survival
      (PFS). RESULTS: In all, 1,422 patients received mFOLFOX6/cediranib 20 mg (n =
      709) or mFOLFOX6/bevacizumab (n = 713). Primary analysis revealed no significant
      difference between arms for PFS (hazard ratio [HR], 1.10; 95% CI, 0.97 to 1.25; P
      = .119), overall survival (OS; HR, 0.95; 95% CI, 0.82 to 1.10; P = .541), or
      overall response rate (46.3% v 47.3%). Median PFS and OS were 9.9 and 22.8 months
      for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab. The PFS
      upper 95% CI was outside the predefined noninferiority limit (HR < 1.2). Common
      adverse events with more than 5% incidence in the cediranib arm included
      diarrhea, neutropenia, and hypertension. Cediranib-treated patients completed
      fewer chemotherapy cycles than bevacizumab-treated patients (median 10 v 12
      cycles). Patient-reported outcomes (PROs) were significantly less favorable in
      cediranib-treated versus bevacizumab-treated patients (P < .001). CONCLUSION:
      Cediranib activity, in terms of PFS and OS, was comparable to that of bevacizumab
      when added to mFOLFOX6; however, the predefined boundary for PFS noninferiority
      was not met. The cediranib safety profile was consistent with previous studies
      but led to less favorable PROs compared with bevacizumab. Investigation of oral
      TKIs in CRC continues.

PMID- 22965963
TI  - Body-surface area-based chemotherapy dosing: appropriate in the 21st century?

PMID- 22965964
TI  - Phase I study of a novel oral Janus kinase 2 inhibitor, SB1518, in patients with
      relapsed lymphoma: evidence of clinical and biologic activity in multiple
      lymphoma subtypes.
AB  - PURPOSE: The Janus kinase 2/signal transducers and activators of transcription
      (JAK2/STAT) pathway plays an important role in the pathogenesis of hematologic
      malignancies. We conducted a phase I dose-finding and
      pharmacokinetic/pharmacodynamic study of SB1518, a potent JAK2 inhibitor, in
      patients with relapsed lymphoma. PATIENTS AND METHODS: Patients with relapsed or
      refractory Hodgkin or non-Hodgkin lymphoma of any type except Burkitt's or CNS
      lymphoma were enrolled. Patient cohorts received escalating doses of SB1518
      orally once daily for 28-day cycles. Response was evaluated after 8 weeks.
      RESULTS: Thirty-four patients received doses of 100 to 600 mg/d. The maximum
      tolerated dose was not reached. Treatment was well tolerated, with mostly grade 1
      and 2 toxicities. Gastrointestinal toxicities were the most common treatment
      related events. Cytopenias were infrequent and modest. Pharmacologically active
      concentrations were achieved at all doses. Dose-related linear increases in area
      under the concentration-time curve were seen on day 1, with no significant
      accumulation on day 15. Mean terminal half-life was 1 to 4 days, and mean time to
      peak concentration ranged from 5 to 9 hours. SB1518 inhibited JAK2 signaling at 4
      hours postdose at all levels. Increases in fms-like tyrosine kinase-3 (FLT-3)
      ligand, reflecting FLT-3 inhibition, were seen in most patients. There were three
      partial responses (>=300 mg/d) and 15 patients with stable disease (SD), with
      most responses lasting longer than 2 months. Seven of 13 SDs had tumor reductions
      of 4% to 46%. CONCLUSION: SB1518 has encouraging activity in relapsed lymphoma,
      providing the first proof-of-principle of the potential therapeutic value of
      targeting the JAK/STAT pathway in lymphoma in the clinical setting.

PMID- 22965965
TI  - Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with
      previously untreated metastatic colorectal cancer: a randomized, double-blind,
      phase III study (HORIZON II).
AB  - PURPOSE: Cediranib is a highly potent inhibitor of vascular endothelial growth
      factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON
      II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus
      Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed
      infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin
      (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated
      metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Eligible patients were
      initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or
      placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib
      studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in
      Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III
      [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With
      Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined
      criteria for continuation. Subsequent patients were randomly assigned 2:1 to the
      cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall
      survival (OS) were coprimary end points. RESULTS: In all, 860 patients received
      cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to
      FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73
      to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for
      placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707;
      median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no
      significant differences in the secondary end points of objective response rate,
      duration of response, or liver resection rate. Median chemotherapy dose-intensity
      was decreased by approximately 10% in patients treated with cediranib. Adverse
      events (AEs) associated with cediranib were manageable. CONCLUSION Addition of
      cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no
      significant difference in OS. The cediranib AE profile was consistent with those
      from previous studies. Because of the lack of improvement in OS, cediranib plus
      an oxaliplatin-based regimen cannot be recommended as a treatment for patients
      with mCRC.

PMID- 22965966
TI  - Cancer of unknown primary: from immunohistochemistry to gene expression
      profiling.

PMID- 22965967
TI  - Acute Myeloid Leukemia (AML): different treatment strategies versus a common
      standard arm--combined prospective analysis by the German AML Intergroup.
AB  - PURPOSE: Identifying true therapeutic progress in patients with acute myeloid
      leukemia (AML) requires a comparison of treatment strategies and results on the
      basis of uniform patient selection. To foster comparability across five clinical
      studies, we introduced a common standard arm combined with a general upfront
      randomization and performed prospective analyses with adjustment for differences
      in prognostic baseline characteristics. PATIENTS AND METHODS: Whereas the
      studies' own regimens differed in chemotherapies, risk adaption, and guidelines
      for allogeneic stem-cell transplantation, the standard arm contained uniform
      cytarabine- and anthracycline-based standard-dose remission induction and high
      dose consolidation courses. RESULTS: Of 2,995 evaluable patients aged 16 to 60
      years, 290 patients were randomly assigned to the common standard arm. Seventy
      percent of the 290 achieved complete remissions (62% with complete recovery, 8%
      with incomplete recovery; 95% CI, 65% to 76%). Five-year survival probabilities
      were 44.3% (95% CI, 37.7% to 50.7%) for overall survival, 44.8% (95% CI, 37.0% to
      52.2%) for relapse-free survival, and 31.5% (95% CI, 25.7% to 37.4%) for event
      free survival. Neither the unadjusted survival probabilities of the Kaplan-Meier
      method nor their adjustment for prognostic variables in multiple Cox regression
      models led to statistically significant different results in the three survival
      end points when the outcomes of each study were compared with the standard arm.
      CONCLUSION: A strictly prospective comparison of different treatment strategies
      in patients with AML did not show clinically relevant outcome differences when
      compared through a common standard treatment arm. The results provide a
      representative basis for further therapeutic approaches.

PMID- 22965968
TI  - American Society of Clinical Oncology guideline on weight-based dosing and its
      impact on trial design.

PMID- 22965969
TI  - Medial regeneration using a biodegradable felt as a scaffold preserves integrity
      and compliance of a canine dissected aorta.
AB  - BACKGROUND: Repair of a dissected aorta involves reattaching the media with
      synthetic glue and/or reinforcement with nonbiodegradable felt. Late
      complications specific to each aspect of this procedure have been reported. We
      attempted to regenerate the media by using biodegradable felt. METHODS AND
      RESULTS: We created a canine model of descending thoracic aortic dissection and
      compared 4 modes of aortic repair: biodegradable polyglycolic acid (PGA) felt in
      the media; PGA with basic fibroblast growth factor (bFGF) in the media; PGA with
      bFGF in the media plus external reinforcement with expanded
      polytetrafluoroethylene; and primary suture closure of the dissected lumen
      (control). Repaired aortic stumps were quantitatively tested for suture pull-out
      strength. Failure force improved 4-fold in all 3 medial reinforcement groups
      compared with controls. Additionally, animals were kept alive for histological
      examination and compliance testing 6 months after repair. Compliance of the
      aortic wall at the anastomotic sites was not essentially affected in the long
      term except in the group with concomitant external reinforcement (55.9 +/- 4.5%
      reduction; P<0.05). In this group, elastic fiber in the media and collagen fiber
      in the adventitia tended to diminish relative to the other groups. Regarding
      vessel density in the repaired false lumen, this external reinforced group had a
      significantly decreased number. Histological derangement was not observed in
      control or medial reinforcement groups. Basic FGF, applied with PGA in the
      dissected lumen, failed to yield additional modifications in this model.
      CONCLUSIONS: Medial reinforcement provides sufficient augmented strength for
      aortic surgical repair. Medial regeneration using biodegradable felt as a
      scaffold preserves histological integrity and compliance in the canine dissected
      aorta.

PMID- 22965970
TI  - The evolution of chemokine release supports a bimodal mechanism of spinal cord
      ischemia and reperfusion injury.
AB  - BACKGROUND: Paraplegia remains a devastating complication of thoracic aortic
      surgery. The mechanism of the antecedent spinal cord ischemia and reperfusion
      injury (IR) remains poorly described. IR involves 2 injuries, an initial ischemic
      insult and subsequent inflammatory amplification of the injury. This mechanism is
      consistent with the clinical phenomenon of delayed onset paraplegia. This study
      sought to characterize the inflammatory response in the spinal cord after IR and
      hypothesized that this would support a bimodal mechanism of injury. METHODS AND
      RESULTS: Male C57Bl/6 mice were subjected to 5 minutes of aortic arch and left
      subclavian occlusion with subsequent reperfusion to generate spinal cord
      ischemia. Functional outcomes were scored at 12-hour intervals. Spinal cords were
      harvested after 0, 6, 12, 18, 24, 36, and 48 hours of reperfusion. Cytokine
      levels were analyzed using a mouse magnetic bead-based multiplex immunoassay.
      Inflammatory chemokine concentrations (interleukin [IL]-1beta, IL-6, keratinocyte
      derived cytokine, macrophage inflammatory protein-1alpha, monocyte chemotactic
      protein-1, RANTES, and tumor necrosis factor-alpha) peaked at 6 hours and 36 to
      48 hours after reperfusion. Functional scores reflected initial gain in function
      with subsequent decline, inversely proportional to cytokine levels.
      Immunofluorescent staining demonstrated microglia activation at 12 and 48 hours.
      CONCLUSIONS: Spinal cord ischemia and reperfusion injury occurs in 2 phases,
      correlating to increases in inflammatory chemokines release and microglial
      activation. These observations chronologically parallel the too-common clinical
      syndrome of delayed-onset paraplegia. Understanding the molecular pathogenesis of
      this injury may allow future intervention to prevent this devastating
      complication.

PMID- 22965971
TI  - Decreased incidence of supravalvar pulmonary stenosis after arterial switch
      operation.
AB  - BACKGROUND: Supravalvar pulmonary stenosis (SVPS) is frequently observed after
      arterial switch. Traditionally the coronary arteries are removed from the
      neopulmonic root by excising the entire sinus of Valsalva. As a result,
      reconstruction of the neopulmonic root requires a pericardial patch encompassing
      two-thirds of the anastomosis between the neopulmonic root and pulmonary artery.
      We present a technique where the coronary arteries are removed as limited buttons
      of sinus tissue, leaving the transected edge of the neopulmonic root intact. We
      hypothesize that maintaining native arterial tissue in the anastomosis between
      the neopulmonic root and the pulmonary artery bifurcation reduces postoperative
      SVPS. METHODS AND RESULTS: We performed a retrospective review of neonates with D
      transposition of the great arteries undergoing arterial switch procedure from
      1996 to 2009. Charts were reviewed, and clinical outcomes recorded for each
      patient. Most recent echocardiograms were evaluated for right ventricular outflow
      tract obstruction. A total of 120 patients received arterial switch using this
      technique. There was 99% survival and no injuries to the coronary arteries
      regardless of anatomy. Total follow-up was 564 patient-years. Mean follow-up at
      last clinical visit was 66 +/- 46 months. Evaluation of the most recent
      outpatient echocardiogram revealed an average peak instantaneous gradient across
      the neopulmonic root of 22.5 +/- 5 mm Hg. Only 7 (5%) patients required
      reintervention (balloon dilation, n=5; surgery, n=2). CONCLUSIONS: Our technique
      of removing the coronary arteries as limited buttons, and anastomosis of the
      pulmonary artery using only native arterial tissue provides excellent midterm
      results with minimal SVPS.

PMID- 22965972
TI  - Hybrid versus Norwood strategies for single-ventricle palliation.
AB  - BACKGROUND: Hybrid and Norwood strategies differ substantially in terms of stage
      II palliative procedures. We sought to compare these strategies with an emphasis
      on survival and reintervention after stage II and subsequent Fontan completion.
      METHODS AND RESULTS: Of 110 neonates with functionally single-ventricle
      physiology who underwent stage I palliation between 2004 and 2010, 75 (69%)
      infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II
      palliation were studied. Survival and reintervention rates after stage II
      palliation, anatomic and physiologic variables at pre-Fontan assessment, and
      Fontan outcomes were compared between the groups. Predictors for reintervention
      were analyzed. Freedom from death/transplant after stage II palliation was
      equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years,
      P=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate
      (P=0.003) and lower Nakata index at pre-Fontan evaluation (P=0.015). Aortic arch
      and atrioventricular valve reinterventions were not different between the groups.
      Ventricular end-diastolic pressure, mean PA pressure, and ventricular function
      were equivalent at pre-Fontan assessment. There were no deaths after Fontan
      completion in either group (Norwood, n=25, hybrid, n=14). CONCLUSIONS: Survival
      after stage II palliation and subsequent Fontan completion is equivalent between
      the groups. The hybrid group had a higher PA reintervention rate and smaller PA
      size. Both strategies achieved adequate physiology for Fontan completion.
      Evolution of the hybrid strategy requires refinement to provide optimal PA
      growth.

PMID- 22965973
TI  - Primary payer status is associated with mortality and resource utilization for
      coronary artery bypass grafting.
AB  - BACKGROUND: Medicaid and uninsured populations are a significant focus of current
      healthcare reform. We hypothesized that outcomes after coronary artery bypass
      grafting (CABG) in the United States is dependent on primary payer status.
      METHODS AND RESULTS: From 2003 to 2007, 1,250,619 isolated CABG operations were
      evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were
      stratified by primary payer status: Medicare, Medicaid, uninsured, and private
      insurance. Hierarchical multiple regression models were applied to assess the
      effect of primary payer status on postoperative outcomes. Unadjusted mortality
      for Medicare (3.3%), Medicaid (2.4%), and uninsured (1.9%) patients were higher
      compared with private insurance patients (1.1%, P<0.001). Unadjusted length of
      stay was longest for Medicaid patients (10.9 +/- 0.04 days) and shortest for
      private insurance patients (8.0 +/- 0.01 days, P<0.001). Medicaid patients
      accrued the highest unadjusted total costs ($113 380 +/- 386, P<0.001).
      Importantly, after controlling for patient risk factors, income, hospital
      features, and operative volume, Medicaid (odds ratio, 1.82; P<0.001) and
      uninsured (odds ratio, 1.62; P<0.001) payer status independently conferred the
      highest adjusted odds of in-hospital mortality. In addition, Medicaid payer
      status was associated with the longest adjusted length of stay and highest
      adjusted total costs (P<0.001). CONCLUSIONS: Medicaid and uninsured payer status
      confers increased risk adjusted in-hospital mortality for patients undergoing
      coronary artery bypass grafting operations. Medicaid was further associated with
      the greatest adjusted length of stay and total costs despite risk factors.
      Possible explanations include delays in access to care or disparate differences
      in health maintenance.

PMID- 22965974
TI  - Radial artery free and T graft patency as coronary artery bypass conduit over a
      15-year period.
AB  - BACKGROUND: The radial artery is often used as the second arterial graft for
      coronary artery bypass grafting. Little is known about the differences in long
      term patency between radial free and T grafts. This study was performed to
      determine long-term radial artery patency over a 15-year period. METHODS AND
      RESULTS: Radial arteries were used as free grafts or T grafts for coronary artery
      bypass grafting over a 15-year period. Patients were contacted to determine if
      postoperative cardiac catheterization was performed and examination of any
      reports and films was performed. Grafts were graded as patent, luminal
      irregularity, or occluded. Each sequential graft was counted separately. Between
      September 1993 and December 2008, 13,926 patients underwent isolated coronary
      artery bypass grafting and 3248 patients had at least one radial artery graft
      used as a conduit. Catheterizations were performed at a mean of 7.4 +/- 3.8 years
      (range, 3 days to 14.4 years) on 372 radial artery grafts (103 free and 269 T) in
      215 patients. Kaplan-Meier freedom from occlusion for radial free and T grafts at
      1 and 10 years was 97.1% and 75.4% and 99.6% and 62.9%, respectively (P=0.146
      free versus T). Kaplan-Meier survival to 15 years was not statistically different
      between free and T graft patients (P=0.5). CONCLUSIONS: In 215 patients with
      postoperative catheterization after coronary artery bypass grafting with a radial
      artery graft, radial free and T grafts had similar and acceptable long-term
      patency to support their use as a coronary artery bypass graft conduit.

PMID- 22965975
TI  - Cost-effectiveness analysis for surgical, angioplasty, or medical therapeutics
      for coronary artery disease: 5-year follow-up of medicine, angioplasty, or
      surgery study (MASS) II trial.
AB  - BACKGROUND: The Second Medicine, Angioplasty, or Surgery Study (MASS II) included
      patients with multivessel coronary artery disease and normal systolic ventricular
      function. Patients underwent coronary artery bypass graft surgery (CABG, n=203),
      percutaneous coronary intervention (PCI, n=205), or medical treatment alone (MT,
      n=203). This investigation compares the economic outcome at 5-year follow-up of
      the 3 therapeutic strategies. METHODS AND RESULTS: We analyzed cumulative costs
      during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment
      was made on the cumulative costs for average event-free time and angina-free
      proportion. Respectively, for event-free survival and event plus angina-free
      survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted
      life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG
      demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were
      $9071.00 for MT; $19,967.00 for PCI; and $18,263.00 for CABG. The paired
      comparison of the event-free costs showed that there was a significant difference
      favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI
      (P=0.01). The event-free plus angina-free costs were $16,553.00, $25,831.00, and
      $24,614.00, respectively. The paired comparison of the event-free plus angina
      free costs showed that there was a significant difference favoring MT versus PCI
      (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI
      (P>0.05). CONCLUSIONS: In the long-term economic analysis, for the prevention of
      a composite primary end point, MT was more cost effective than CABG, and CABG was
      more cost-effective than PCI. CLINICAL TRIAL REGISTRATION INFORMATION:
      www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

PMID- 22965976
TI  - Benefits of off-pump coronary artery bypass grafting in high-risk patients.
AB  - BACKGROUND: The benefits of off-pump coronary artery bypass graft (OPCAB)
      compared with conventional on-pump coronary artery bypass graft (CCAB) remain
      controversial. Thus, it is important to investigate which patient subgroups may
      benefit the most from OPCAB rather than CCAB. METHODS AND RESULTS: Among the
      patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto
      Registry (a registry of first-time percutaneous coronary intervention and
      coronary artery bypass graft patients in Japan), 2468 patients undergoing
      coronary artery bypass graft were entered into the study (mean age, 67 +/- 9
      years). Predicted risk of operative mortality (PROM) of each patient was
      calculated by logistic EuroSCORE. Patients were divided into tertile based on
      their PROM. Mortality rates and the incidences of cardiovascular events were
      compared between CCAB and OPCAB within each PROM tertile using propensity score
      analysis. A total of 1377 patients received CCAB whereas 1091 received OPCAB.
      Adjusted 30-day mortality was not significantly different between CCAB and OPCAB
      patients regardless of their PROM range. However, the odds ratio of 30-day stroke
      in CCAB compared with OPCAB in the high-risk tertile was 8.30 (95% confidence
      interval, 2.25-30.7; P<0.01). Regarding long-term outcomes, hazard ratio of
      stroke in CCAB compared with OPCAB in the high-risk tertile was 1.80 (95%
      confidence interval, 1.07-3.02; P=0.03). Nevertheless, hazard ratio of overall
      mortality in the high-risk tertile was 1.44 (95% confidence interval, 0.98-2.11;
      P=0.06), indicating no statistically significant difference between the 2
      procedures. CONCLUSIONS: OPCAB as opposed to CCAB is associated with short-term
      and long-term benefits in stroke prevention in patients at higher risk as
      estimated by EuroSCORE. No survival benefit of OPCAB was shown regardless of
      preoperative risk level.

PMID- 22965977
TI  - Effect of complete revascularization on 10-year survival of patients with stable
      multivessel coronary artery disease: MASS II trial.
AB  - BACKGROUND: The importance of complete revascularization remains unclear and
      contradictory. This current investigation compares the effect of complete
      revascularization on 10-year survival of patients with stable multivessel
      coronary artery disease (CAD) who were randomly assigned to percutaneous coronary
      intervention (PCI) or coronary artery bypass graft (CABG). METHODS AND RESULTS:
      This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study
      (MASS II), which is a randomized trial comparing treatments in patients with
      stable multivessel CAD, and preserved systolic ventricular function. We analyzed
      patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival
      free of overall mortality of patients who underwent complete (CR) or incomplete
      revascularization (IR) was compared. Of the 408 patients randomly assigned to
      mechanical revascularization, 390 patients (95.6%) underwent the assigned
      treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8%
      of those in the CABG group and 36.2% in the PCI group (P=0.001). The IR group had
      more prior myocardial infarction than the CR group (56.2% * 39.2%, P=0.01).
      During a 10-year follow-up, the survival free of cardiovascular mortality was
      significantly different among patients in the 2 groups (CR, 90.6% versus IR,
      84.4%; P=0.04). This was mainly driven by an increased cardiovascular specific
      mortality in individuals with incomplete revascularization submitted to PCI
      (P=0.05). CONCLUSIONS: Our study suggests that in 10-year follow-up, CR compared
      with IR was associated with reduced cardiovascular mortality, especially due to a
      higher increase in cardiovascular-specific mortality in individuals submitted to
      PCI. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.controlled
      trials.com. REGISTRATION NUMBER: ISRCTN66068876.

PMID- 22965978
TI  - Risks of death and end-stage renal disease after surgical compared with
      percutaneous coronary revascularization in elderly patients with chronic kidney
      disease.
AB  - BACKGROUND AND PURPOSE: Revascularization by coronary artery bypass graft (CABG)
      surgery or percutaneous coronary intervention (PCI) is frequently deferred in
      patients with chronic kidney disease (CKD) to avoid precipitating end-stage renal
      disease (ESRD), but reliable estimates of absolute and relative risks of death
      and ESRD after CABG and PCI are unavailable. METHODS AND RESULTS: CKD patients
      undergoing CABG (n=4547) or PCI (n=8620) were identified and tracked using the 5%
      Medicare sample. The cumulative incidence of ESRD and death were reported for
      observed events. A Cox model with the Fine-Gray method was used to account for
      competing risks in assessing relative hazards of death and ESRD. Three-year
      cumulative incidence of ESRD was lower (CABG, 6.8%; PCI, 5.4%) than death (CABG,
      28.3%; PCI, 32.8%). The adjusted hazard ratio of death was higher during the
      first 3 months after CABG than after PCI (1.25; 95% confidence interval, 1.12
      1.40; P<0.001), but lower from 6 months onward (0.61; 95% confidence interval,
      0.55-0.69). Conversely, risk of ESRD after CABG was higher during the first 3
      months (1.59; 95% confidence interval, 1.27-2.01; P<0.001), but was not
      statistically significant from 3 months onward. The adjusted hazard ratio of
      combined death or ESRD was similar to death. CONCLUSIONS: Among CKD patients
      undergoing coronary revascularization, death is more frequent than ESRD. The
      incidence of ESRD was lower throughout follow-up after PCI, but long-term risks
      of death or combined death and ESRD were lower after CABG. Our data suggest
      better overall clinical outcomes with CABG than with PCI in CKD patients.

PMID- 22965979
TI  - Coronary artery bypass grafting using the radial artery: clinical outcomes,
      patency, and need for reintervention.
AB  - BACKGROUND: Radial artery (RA) grafts are an attractive second arterial conduit
      after the left internal thoracic artery (LITA) for coronary artery bypass graft
      (CABG) surgery. However, long-term outcomes and the need for subsequent
      reintervention have not been defined. METHODS AND RESULTS: We performed a
      retrospective cohort study of our single institution's 16-year experience with
      1851 consecutive patients (average age, 58 years; 82% men, 36% diabetic)
      undergoing primary, isolated CABG with the LITA, RA, and saphenous vein as
      needed. Average grafts per patient were 3.8, with 2.4 arterial grafts per
      patient. Survival was determined using the Social Security Death Index. Grafts
      were nonpatent if they had a >50% stenosis, a string sign, or were occluded. Five
      patients (0.3%) died in hospital and 0.8% had a myocardial infarction, 1.1% a
      stroke, and 0.6% renal failure. Kaplan-Meier-estimated 1-, 5-, 10-, and 15-year
      survival was 99%, 96%, 89%, and 75%, respectively. Of the cohort, 278 symptomatic
      patients underwent cardiac catheterization at our institution an average of 5.0+/
      3.8 years (range, 0.1-12 years) after CABG. Overall RA (n=420 grafts) patency was
      82% and SV (n=364 grafts) patency, 47% (P<0.0001). LITA (n=287 grafts including 9
      sequential grafts) patency was 85% and right internal thoracic artery (n=15
      grafts) patency was 80% (P=0.6). RA patency was not different from LITA patency
      (P=0.3). Overall freedom from catheterization, percutaneous coronary
      intervention, and CABG was 85%, 97%, and 99%, respectively. CONCLUSIONS: RA
      grafting is a highly effective revascularization strategy providing excellent
      short and long-term outcomes with very low rates of reintervention. RA patency is
      similar to LITA patency and is much better than SV patency. RA grafting should be
      more widely utilized in patients undergoing CABG.

PMID- 22965980
TI  - Clampless off-pump versus conventional coronary artery revascularization: a
      propensity score analysis of 788 patients.
AB  - BACKGROUND: This study aimed to assess if clampless off-pump coronary artery
      bypass grafting (CABG) decreases risk-adjusted mortality, stroke rate, and
      morbidity in unselected patients in comparison to conventional CABG. METHODS AND
      RESULTS: Between July 2009 and November 2010, data of 1282 consecutive patients
      undergoing isolated CABG were prospectively recorded. In 30.8% (n=395), clampless
      off-pump revascularization was used, either with the PAS-Port automated central
      venous anastomosis system (n=310) or as total arterial revascularization without
      central anastomoses (n=85). Propensity score (PS) matching was performed based on
      15 preoperative risk variables to correct for selection bias. In-hospital
      mortality and stroke rate as primary end point, as well as major complications
      and follow-up outcome of clampless off-pump (lessOPCAB) and conventional CABG
      (cCABG) were compared in 394 matched patient pairs (total: 788 patients). The
      clampless off-pump technique decreased the in-hospital rate of death (odds ratio,
      0.25; 95% confidence interval, 0.05-1.18, P=0.080) and stroke (odds ratio, 0.36;
      95% confidence interval, 0.13-0.99, P=0.048) significantly. Complications such as
      low cardiac output syndrome, prolonged ventilation and rethoracotomy were also
      reduced by lessOPCAB. Over a 2-year follow-up period overall survival,
      cerebrovascular and major adverse event rate were significantly lower in the
      lessOPCAB group, while the repeat revascularization rate was comparable.
      CONCLUSIONS: In a retrospective PS-matched analysis, clampless off-pump CABG
      lowers mortality, stroke rate and other morbidity in an unselected group of
      patients with coronary artery disease.

PMID- 22965981
TI  - Three-dimensional echocardiographic analysis of mitral annular dynamics:
      implication for annuloplasty selection.
AB  - BACKGROUND: Proponents of flexible annuloplasty rings have hypothesized that such
      devices maintain annular dynamics. This hypothesis is based on the supposition
      that annular motion is relatively normal in patients undergoing mitral valve
      repair. We hypothesized that mitral annular dynamics are impaired in ischemic
      mitral regurgitation and myxomatous mitral regurgitation. METHODS AND RESULTS: A
      Philips iE33 echocardiographic module and X7-2t probe were used to acquire full
      volume real-time 3-dimensional transesophageal echocardiography loops in 11
      normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients
      with myxomatous mitral regurgitation. Image analysis was performed using Tomtec
      Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was
      selected for the initiation of annular tracking using the semiautomated program.
      Continuous parameters were normalized in time to provide for uniform systolic and
      diastolic periods. Both ischemic mitral regurgitation (9.98 +/- 155 cm(2)) and
      myxomatous mitral regurgitation annuli (13.29 +/- 3.05 cm(2)) were larger in area
      than normal annuli (7.95 +/- 1.40 cm(2)) at midsystole. In general, ischemic
      mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral
      regurgitation, annular dynamics were also markedly abnormal with the mitral
      annulus dilating rapidly in early systole in response to rising ventricular
      pressure. CONCLUSIONS: In both ischemic mitral regurgitation and myxomatous
      mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible
      annuloplasty devices used in mitral valve repair are, therefore, unlikely to
      result in either normal annular dynamics or normal anatomy.

PMID- 22965982
TI  - Modulation of transforming growth factor-beta signaling and extracellular matrix
      production in myxomatous mitral valves by angiotensin II receptor blockers.
AB  - BACKGROUND: Little is known about the pathophysiology of myxomatous degeneration
      of the mitral valve, the pathological hallmark of mitral valve prolapse,
      associated with symptomatic mitral regurgitation, heart failure, and death.
      Excess transforming growth factor (TGF)-beta signaling is known to cause mitral
      valve degeneration and regurgitation in a mouse model of Marfan syndrome. We
      examined if TGF-beta signaling is dysregulated in clinical specimens of sporadic
      mitral valve prolapse compared with explanted nondiseased mitral valves and we
      tested the effects of angiotensin II receptor blockers on TGF-beta signaling in
      cultured human mitral valve cells. METHODS AND RESULTS: Operative specimens,
      cultured valve tissues, and cultured valvular interstitial cells were obtained
      from patients with mitral valve prolapse undergoing mitral valve repair or from
      organ donors without mitral valve disease. Increased extracellular matrix in
      diseased valve tissue correlated with an upregulation of TGF-beta expression and
      signaling as evidenced by SMAD2/3 phosphorylation. Both TGF-beta ligand and
      signaling mediators colocalized primarily to valvular interstitial cells
      suggesting autocrine/paracrine activation. In cultured valve tissue, exogenous
      TGF-beta increased basal extracellular matrix production, whereas serological
      neutralization of TGF-beta inhibited disease-driven extracellular matrix
      overproduction. TGF-beta-induced extracellular matrix production in cultured
      valvular interstitial cells was dependent on SMAD2/3 and p38 signaling and was
      inhibited by angiotensin II receptor blockers. CONCLUSIONS: TGF-beta has a
      profibrotic role in the pathogenesis of sporadic mitral valve prolapse.
      Attenuation of TGF-beta signaling by angiotensin II receptor blockers may
      represent a mechanistically based strategy to modulate the pathological
      progression of mitral valve prolapse in patients.

PMID- 22965983
TI  - Long-term clinical and echocardiographic follow-up of the Freestyle stentless
      aortic bioprosthesis.
AB  - BACKGROUND: Stentless aortic bioprostheses were designed to provide enhanced
      hemodynamic performance and potentially greater longevity. The present report
      describes the outcomes of patients with the Freestyle stentless bioprosthesis
      followed for <=18 years. METHODS AND RESULTS: Between 1993 and 2011, 430 patients
      underwent primary aortic valve replacement with a Freestyle bioprosthesis in the
      subcoronary position. Mean age was 68.2 +/- 8.2 years. All of the clinical and
      echocardiographic data were collected prospectively. Mean overall follow-up was
      9.1 +/- 4.4 years and was complete in all of the patients. In-hospital mortality
      was 3.5% (n=15). Overall, 10- and 15-year survival were 60.7% and 35.0%,
      respectively. Fifty-one patients required reoperation during follow-up, including
      27 for structural valve deterioration (SVD). Overall, freedom from reoperation
      was 91.0% and 75.0% at 10 and 15 years, whereas freedom from reoperation for SVD
      was 95.9% and 82.3%, respectively. At 10 and 15 years, freedom from reoperation
      for SVD was 94.0% and 62.6% for patients <60 years of age and 96.3% and 88.4% for
      patients >=60 years of age (P=0.002). The median time to explant for SVD was 10.7
      years. SVD presented mostly as acute, severe aortic insufficiency attributed to
      leaflet tear (77.8%). The independent risk factors for reoperation for SVD were
      age <60 years (P=0.001) and dyslipidemia (P=0.02). CONCLUSIONS: Aortic valve
      replacement with the Freestyle bioprosthesis in a subcoronary position provides
      good long-term clinical and echocardiographic outcomes for patients >60 years of
      age. Severe aortic insufficiency with leaflet tear is the major mode of SVD
      leading to reoperation in these patients.

PMID- 22965985
TI  - Mitral valve repair for medically refractory functional mitral regurgitation in
      patients with end-stage renal disease and advanced heart failure.
AB  - BACKGROUND: Information regarding patient selection for mitral valve repair for
      chronic kidney disease or end-stage renal disease (ESRD) with severe heart
      failure (HF) as well as outcome is limited. METHODS AND RESULTS: We classified
      208 patients with advanced HF symptoms (Stage C/D) undergoing mitral valve repair
      for functional mitral regurgitation into 3 groups: estimated glomerular
      filtration rate >=30 mL/min/1.73 m(2) (control group, n=144); estimated
      glomerular filtration rate <30 mL/min/1.73 m(2), not dependent on hemodialysis
      (late chronic kidney disease group, n=45), and ESRD on hemodialysis (ESRD group,
      n=19; preoperative hemodialysis duration 83 +/- 92 months). Follow-up was
      completed with a mean duration of 49 +/- 25 months. Postoperative (1-month)
      cardiac catheterization showed that left ventricular end-systolic volume index
      decreased from 109 +/- 38 to 79 +/- 41, 103 +/- 31 to 81 +/- 31, and 123 +/- 40
      to 76 +/- 34 mL/m(2), in the control, late chronic kidney disease, and ESRD
      groups, respectively. Left ventricular end-diastolic pressure decreased, whereas
      cardiac index increased in all groups with no intergroup differences for those
      postoperative values. Freedom from mortality and HF readmission at 5 years was
      18% +/- 7% in late chronic kidney disease (P<0.0001 versus control, P=0.01 versus
      ESRD), and 64% +/- 12% in ESRD (P=1 versus control) as compared with 52% +/- 5%
      in the control group (median event-free survival, 26, 67, and 63 months,
      respectively). CONCLUSIONS: Mitral valve repair for medically refractory
      functional mitral regurgitation in patients with advanced HF yielded improvements
      in left ventricular function and hemodynamics irrespective of preoperative renal
      function status. Patients with ESRD showed favorable late outcome in terms of
      freedom from mortality and readmission for HF as compared with those with late
      chronic kidney disease. Further studies are needed to assess the survival
      benefits of mitral valve repair in patients with ESRD and advanced HF.

PMID- 22965984
TI  - Safe genetic modification of cardiac stem cells using a site-specific integration
      technique.
AB  - BACKGROUND: Human cardiac progenitor cells (hCPCs) are a promising cell source
      for regenerative repair after myocardial infarction. Exploitation of their full
      therapeutic potential may require stable genetic modification of the cells ex
      vivo. Safe genetic engineering of stem cells, using facile methods for site
      specific integration of transgenes into known genomic contexts, would
      significantly enhance the overall safety and efficacy of cellular therapy in a
      variety of clinical contexts. METHODS AND RESULTS: We used the phiC31 site
      specific recombinase to achieve targeted integration of a triple fusion reporter
      gene into a known chromosomal context in hCPCs and human endothelial cells.
      Stable expression of the reporter gene from its unique chromosomal integration
      site resulted in no discernible genomic instability or adverse changes in cell
      phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation
      propensity, cellular proliferative rate, and global gene expression profile when
      compared with unaltered control hCPCs. Expression of the triple fusion reporter
      gene enabled multimodal assessment of cell fate in vitro and in vivo using
      fluorescence microscopy, bioluminescence imaging, and positron emission
      tomography. Intramyocardial transplantation of genetically modified hCPCs
      resulted in significant improvement in myocardial function 2 weeks after cell
      delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also
      demonstrated the feasibility and therapeutic efficacy of genetically modifying
      differentiated human endothelial cells, which enhanced hind limb perfusion
      (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging.
      CONCLUSIONS: The phiC31 integrase genomic modification system is a safe,
      efficient tool to enable site-specific integration of reporter transgenes in
      progenitor and differentiated cell types.

PMID- 22965986
TI  - Evidence of a vicious cycle in mitral regurgitation with prolapse: secondary
      tethering attributed to primary prolapse demonstrated by three-dimensional
      echocardiography exacerbates regurgitation.
AB  - BACKGROUND: In patients with mitral valve prolapse, nonprolapsed leaflets are
      often apically tented. We hypothesized that secondary left ventricular dilatation
      attributed to primary mitral regurgitation (MR) causes papillary muscle (PM)
      displacement, resulting in this leaflet tenting/tethering, and that secondary
      tethering further exacerbates malcoaptation and contributes to MR severity.
      METHODS AND RESULTS: Three-dimensional transesophageal echocardiography was
      performed in 25 patients with posterior mitral leaflet prolapse with an intact
      anterior mitral leaflet (AML) and 20 controls. From 3D zoom data sets, 11
      equidistant antero-posterior cut planes of the mitral valve at midsystole were
      obtained. In each plane, tenting area of nonprolapsed leaflet and prolapse area
      of prolapsed leaflet were measured. Prolapse/tenting volume of each region was
      obtained as the product of interslice distance and the prolapse/tenting area. AML
      tenting volume and whole leaflet prolapse/tenting volume were then obtained. The
      PM tethering distance between PM tips and anterior mitral annulus was measured
      from 3D full-volume data sets. The severity of MR was quantified by vena
      contracta area extracted from color 3D transesophageal echocardiography data
      sets. AML tenting volume was significantly larger in patients with posterior
      mitral leaflet prolapse compared with that in controls (1.2 +/- 0.5 versus 0.6 +/
      0.2 mL/m(2); P<0.001). Multivariate regression analysis identified independent
      contribution to AML tenting volume from an increase in PM tethering distance.
      Multivariate regression analysis identified independent contributions to MR
      severity (vena contracta area) from both whole leaflet tenting volume (r=0.44;
      P<0.05) and prolapse volume (r=0.44; P<0.05). AML tenting volume decreased along
      with left ventricular volume and PM tethering distance postrepair (n=8; P<0.01).
      CONCLUSIONS: These results suggest that primary mitral valve prolapse with MR
      causes secondary mitral leaflet tethering with PM displacement by left
      ventricular dilatation, which further exacerbates valve leakage, constituting a
      vicious cycle that would suggest a pathophysiologic rationale for early surgical
      repair.

PMID- 22965987
TI  - Cross-talk between the Toll-like receptor 4 and Notch1 pathways augments the
      inflammatory response in the interstitial cells of stenotic human aortic valves.
AB  - BACKGROUND AND PURPOSE: Calcific aortic stenosis is a chronic inflammatory
      disease, and aortic valve interstitial cells (AVIC) play an important role in
      valvular inflammation. Whereas AVIC from stenotic aortic valves exhibit an
      augmented response to Toll-like receptor 4 (TLR4) stimulation, the underlying
      mechanism is unclear. This study tested the hypothesis that an excessive cross
      talk between the TLR4 and Notch1 pathways is responsible for augmentation of the
      inflammatory response to lipopolysaccharide (LPS) in AVIC of stenotic valves.
      METHODS AND RESULTS: Human AVIC were isolated from normal and stenotic leaflets.
      Nuclear factor kappa-B (NF-kappaB) activation and production of interleukin-8,
      monocyte chemoattactrant protein-1, and intercellular adhesion molecule-1 were
      analyzed after treatment with LPS. The role of Notch1 in the inflammatory
      response was determined using inhibitor, siRNA, and specific ligand. Cells from
      diseased valves produced greater levels of chemokines and intercellular adhesion
      molecule-1 that are associated with enhanced NF-kappaB activation. Interestingly,
      diseased cells exhibited augmented Jagged1 release and Notch1 activation after
      TLR4 stimulation. Inhibition and silencing of Notch1 each resulted in greater
      suppression of the TLR4-induced inflammatory response in diseased cells.
      Conversely, activation of Notch1 with a specific ligand, Jagged1, enhanced the
      LPS-induced inflammatory response in normal AVIC. Further, Notch1 intracellular
      domain was coimmunoprecipited with the inhibitor of NF-kappaB kinase after LPS
      stimulation, and inhibition of Notch1 abrogated the difference in the level of NF
      kappaB activation between diseased and normal cells. CONCLUSION: Notch1 enhances
      the inflammatory response to TLR4 stimulation in human AVIC through modulating NF
      kappaB activation. Excessive cross-talk between the TLR4 and Notch1 pathways is
      responsible for augmentation of the TLR4 response in AVIC of stenotic valves.

PMID- 22965988
TI  - How do annuloplasty rings affect mitral annular strains in the normal beating
      ovine heart?
AB  - BACKGROUND: We hypothesized that annuloplasty ring implantation alters mitral
      annular strains in a normal beating ovine heart preparation. METHODS AND RESULTS:
      Sheep had 16 radiopaque markers sewn equally spaced around the mitral annulus.
      Edwards Cosgrove partial flexible band (COS; n=12), St Jude complete rigid saddle
      shaped annuloplasty ring (RSA; n=10), Carpentier-Edwards Physio (PHY; n=11),
      Edwards IMR ETlogix (ETL; n=11), and GeoForm (GEO; n=12) annuloplasty rings were
      implanted in a releasable fashion. Four-dimensional marker coordinates were
      obtained using biplane videofluoroscopy with the ring inserted (ring) and after
      ring release (control). From marker coordinates, a functional spatio-temporal
      representation of each annulus was generated through a best fit using 16
      piecewise cubic Hermitian splines. Absolute total mitral annular ring strains
      were calculated from the relative change in length of the tangent vector to the
      annular curve as strains occurring from control to ring state at end-systole. In
      addition, average Green-Lagrange strains occurring from control to ring state at
      end-systole along the annulus were calculated. Absolute total mitral annular ring
      strains were smallest for COS and greatest for ETL. Strains for RSA, PHY, and GEO
      were similar. Except for COS in the septal mitral annular segment, all rings
      induced compressive strains along the entire annulus, with greatest values
      occurring at the lateral mitral annular segment. CONCLUSIONS: In healthy, beating
      ovine hearts, annuloplasty rings (COS, RSA, PHY, ETL, and GEO) induce compressive
      strains that are predominate in the lateral annular region, smallest for flexible
      partial bands (COS) and greatest for an asymmetrical rigid ring type with
      intrinsic septal-lateral downsizing (ETL). However, the ring type with the most
      drastic intrinsic septal-lateral downsizing (GEO) introduced strains similar to
      physiologically shaped rings (RSA and PHY), indicating that ring effects on
      annular strain profiles cannot be estimated from the degree of septal-lateral
      downsizing.

PMID- 22965989
TI  - Cerebral microembolization after bioprosthetic aortic valve replacement:
      comparison of warfarin plus aspirin versus aspirin only.
AB  - BACKGROUND: No human physiological data exists on whether aspirin only is as
      effective as warfarin plus aspirin in preventing cerebral microembolization in
      the early postoperative period after bioprosthetic aortic valve replacement
      (bAVR). METHODS AND RESULTS: We prospectively enrolled 56 patients who had no
      other indication for oral anticoagulation, who underwent bAVR and received, in an
      open-label fashion, either daily warfarin (for INR 2.0-3.0) plus 81 mg of aspirin
      (n=28) or 325 mg of aspirin only (n=28). Cerebral microembolization was
      quantified at 4 hours (baseline) and at 1 month postoperatively, by recording 1
      hour bilateral middle cerebral artery (MCA) microembolic signals (MES). Platelet
      function analysis (PFA) of closure times (CT) on collagen was also used as a
      marker of platelet-dependent activation. Follow-up to 1 year was complete.
      Preoperative demographics and baseline platelet function were equivalent in both
      groups. There was no mortality, stroke, or transient ischemic attack at 1 year in
      either group. No significant differences were found in the proportion of patients
      with MES among those receiving warfarin plus aspirin versus aspirin only, at
      baseline (68% versus 82%, respectively; P=0.4) and at 1 month (46% versus 43%;
      P=1.0) after bAVR. The total MES and PFA were also equivalent between groups, at
      baseline and follow-up. CONCLUSIONS: Early after bAVR, the effects of these 2
      antithrombotic regimens on cerebral microembolization and platelet function are
      equivalent. These data bring new mechanistic support to the premise that aspirin
      only may safely be used early after bAVR in patients who have no other indication
      for oral anticoagulation.

PMID- 22965990
TI  - Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem
      cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model.
AB  - BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs)
      are a promising source of cells for regenerating myocardium. However, several
      issues, especially the large-scale preparation of hiPS-CMs and elimination of
      undifferentiated iPS cells, must be resolved before hiPS cells can be used
      clinically. The cell-sheet technique is one of the useful methods for
      transplanting large numbers of cells. We hypothesized that hiPS-CM-sheet
      transplantation would be feasible, safe, and therapeutically effective for the
      treatment of ischemic cardiomyopathy. METHODS AND RESULTS: Human iPS cells were
      established by infecting human dermal fibroblasts with a retrovirus carrying
      Oct3/4, Sox2, Klf4, and c-Myc. Cardiomyogenic differentiation was induced by WNT
      signaling molecules, yielding hiPS-CMs that were almost 90% positive for alpha
      actinin, Nkx2.5, and cardiac troponin T. hiPS-CM sheets were created using
      thermoresponsive dishes and transplanted over the myocardial infarcts in a
      porcine model of ischemic cardiomyopathy induced by ameroid constriction of the
      left anterior descending coronary artery (n=6 for the iPS group receiving sheet
      transplantation and the sham-operated group; both groups received tacrolimus
      daily). Transplantation significantly improved cardiac performance and attenuated
      left ventricular remodeling. hiPS-CMs were detectable 8 weeks after
      transplantation, but very few survived long term. No teratoma formation was
      observed in animals that received hiPS-CM sheets. CONCLUSIONS: The culture system
      used yields a large number of highly pure hiPS-CMs, and hiPS-CM sheets could
      improve cardiac function after ischemic cardiomyopathy. This newly developed
      culture system and the hiPS-CM sheets may provide a basis for the clinical use of
      hiPS cells in cardiac regeneration therapy.

PMID- 22965991
TI  - Survival in patients with severe ischemic cardiomyopathy undergoing
      revascularization versus medical therapy: association with end-systolic volume
      and viability.
AB  - BACKGROUND: The value of assessment of viability as a predictor of surgical
      revascularization benefit in ischemic cardiomyopathy has recently been questioned
      in a large trial. We sought to determine whether the contribution of viability as
      myocardial scar burden (SB) to predict revascularization outcomes could be
      modulated by end-systolic volume index (ESVi). METHODS AND RESULTS: Delayed
      hyperenhancement-MRI was obtained in 450 patients with >=70% stenosis in >=1
      epicardial coronary artery (75% men; median age, 62.8 +/- 10.7 years; mean left
      ventricular ejection fraction, 23 +/- 9%; mean ESVi, 115 +/- 50 mL) from 2002 to
      2006. SB was quantified as scar percentage (infarcted mass/total left ventricular
      mass). Subsequent surgical revascularization was performed in 245 (54%) patients
      and subsequent percutaneous coronary interventions were performed in 28 (6%)
      patients. A propensity score was developed for revascularization. Cox
      proportional hazards models of all-cause mortality were used for risk adjustment.
      Over a mean follow-up of 5.8 +/- 2.7 years, 186 (41%) deaths occurred. After
      adjusting for prior revascularization, sex, diabetes, age, use of cardiac
      resynchronization therapy, implantable cardioverter defibrillator, mitral
      regurgitation, and mitral valve procedures; an interaction between scar
      percentage and ESVi (P=0.016) and an interaction between post-MRI
      revascularization and ESVi (P=0.0017) were independently associated with
      mortality. ESVi demonstrated a significant interaction with revascularization and
      female sex, such that enhanced survival was associated with ESVi. ESVi also
      showed an interaction with SB; better survival was associated with lower volumes
      and less scar. CONCLUSIONS: ESVi and SB provide independent, incremental
      prognostic value in patients with severe ischemic cardiomyopathy. The risk
      associated with SB should not be assessed in isolation.

PMID- 22965992
TI  - Experimental abdominal aortic aneurysm formation is mediated by IL-17 and
      attenuated by mesenchymal stem cell treatment.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) formation is characterized by
      inflammation, smooth muscle activation and matrix degradation. This study tests
      the hypothesis that CD4+ T-cell-produced IL-17 modulates inflammation and smooth
      muscle cell activation, leading to the pathogenesis of AAA and that human
      mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA
      formation. METHODS AND RESULTS: Human aortic tissue demonstrated a significant
      increase in IL-17 and IL-23 expression in AAA patients compared with control
      subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6
      (wild-type; WT), IL-23(-/-) or IL-17(-/-) mice using an elastase-perfusion model.
      Heat-inactivated elastase was used as control. On days 3, 7, and 14 after
      perfusion, abdominal aorta diameter was measured by video micrometry, and aortic
      tissue was analyzed for cytokines, cell counts, and IL-17-producing CD4+ T cells.
      Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-alpha, MIP
      1alpha, and IFN-gamma) was significantly attenuated in elastase-perfused IL-17(-/
      ) and IL-23(-/-) mice compared with WT mice on day 14. Cellular infiltration
      (especially IL-17-producing CD4+ T cells) was significantly attenuated in
      elastase-perfused IL-17(-/-) mice compared with WT mice on day 14. Primary aortic
      smooth muscle cells were significantly activated by elastase or IL-17 treatment.
      Furthermore, MSC treatment significantly attenuated AAA formation and IL-17
      production in elastase-perfused WT mice. CONCLUSIONS: These results demonstrate
      that CD4+ T-cell-produced IL-17 plays a critical role in promoting inflammation
      during AAA formation and that immunomodulation of IL-17 by MSCs can offer
      protection against AAA formation.

PMID- 22965993
TI  - A strong regenerative ability of cardiac stem cells derived from neonatal hearts.
AB  - BACKGROUND: Human cardiac stem cells (CSCs) promote myocardial regeneration in
      adult ischemic myocardium. The regenerative capacity of CSCs in very young
      patients with nonischemic congenital heart defects has not been explored. We
      hypothesized that isolated neonatal-derived CSCs may have a higher regenerative
      ability than adult-derived CSCs and might address the structural deficiencies of
      congenital heart disease. METHODS AND RESULTS: Human specimens were obtained
      during routine cardiac surgical procedures from right atrial appendage tissue
      discarded from 2 age groups: neonates and adults patients. We developed a
      reproducible isolation method that generated cardiosphere-derived cells (CDCs),
      regardless of starting tissue weight or age. Neonatal-derived CDCs demonstrated
      increased number of cardiac progenitor cells expressing c-kit(+), flk-1, and
      Islet-1 by flow cytometry and immunofluorescence. When transplanted into
      infarcted myocardium, neonatal-derived CDCs had a significantly higher ability to
      preserve myocardial function, prevent adverse remodeling, and enhance blood
      vessel preservation and/or formation when compared with adult-derived CDCs. Last,
      neonatal-derived CDCs were more cardiomyogenic than adult-derived CDCs when
      cocultured with neonatal cardiomyocytes and displayed enhanced angiogenic
      function compared with adult-derived CDCs. CONCLUSIONS: Neonatal-derived CDCs
      have a strong regenerative ability when compared with adult-derived CDCs that may
      depend on angiogenic cytokines and an increase prevalence of stem cells. This has
      important implications in the potential use of CDCs in future clinical trials.

PMID- 22965994
TI  - Administration of cardiac stem cells in patients with ischemic cardiomyopathy:
      the SCIPIO trial: surgical aspects and interim analysis of myocardial function
      and viability by magnetic resonance.
AB  - BACKGROUND: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of
      autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of
      ischemic etiology undergoing coronary artery bypass grafting (CABG). In the
      present study, we report the surgical aspects and interim cardiac magnetic
      resonance (CMR) results. METHODS AND RESULTS: A total of 33 patients (20 CSC
      treated and 13 control subjects) met final eligibility criteria and were enrolled
      in SCIPIO. CSCs were isolated from the right atrial appendage harvested and
      processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross
      clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase
      in both LVEF (from 27.5 +/- 1.6% to 35.1 +/- 2.4% [P=0.004, n=8] and 41.2 +/-
      4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and
      regional EF in the CSC-infused territory. Infarct size (late gadolinium
      enhancement) decreased after CSC infusion (by manual delineation: -6.9 +/- 1.5 g
      [-22.7%] at 4 months [P=0.002, n=9] and -9.8 +/- 3.5 g [-30.2%] at 12 months
      [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 +/- 2.5 g [-49.7%]
      at 4 months [P=0.001] and -14.7 +/- 3.9 g [-58.6%] at 12 months [P=0.013]),
      whereas LV viable mass increased (+11.6 +/- 5.1 g at 4 months after CSC infusion
      [P=0.055] and +31.5 +/- 11.0 g at 12 months [P=0.035]). CONCLUSIONS: Isolation of
      CSCs from cardiac tissue obtained in the operating room is feasible and does not
      alter practices during CABG surgery. CMR shows that CSC infusion produces a
      striking improvement in both global and regional LV function, a reduction in
      infarct size, and an increase in viable tissue that persist at least 1 year and
      are consistent with cardiac regeneration. CLINICAL TRIAL REGISTRATION: This study
      is registered with clinicaltrials.gov, trial number NCT00474461.

PMID- 22965995
TI  - Effects of red wine and vodka on collateral-dependent perfusion and
      cardiovascular function in hypercholesterolemic swine.
AB  - BACKGROUND: Moderate consumption of alcohol, particularly red wine, has been
      shown to decrease cardiac risk. We used a hypercholesterolemic swine model of
      chronic ischemia to examine the effects of 2 alcoholic beverages on the heart.
      METHODS AND RESULTS: Yorkshire swine fed a high-cholesterol diet underwent left
      circumflex ameroid constrictor placement to induce chronic ischemia at 8 weeks of
      age. One group (HCC, n=9) continued on the diet alone, the second (HCW, n=8) was
      supplemented with red wine (pinot noir, 12.5% alcohol, 375 mL daily), and the
      third (HCV, n=9) was supplemented with vodka (40% alcohol, 112 mL daily). After 7
      weeks, cardiac function was measured, and ischemic myocardium was harvested for
      analysis of perfusion, myocardial fibrosis, vessel function, protein expression,
      oxidative stress, and capillary density. Platelet function was measured by
      aggregometry. Perfusion to the ischemic territory as measured by microsphere
      injection was significantly increased in both HCW and HCV compared with HCC at
      rest, but in only the HCW group under ventricular pacing. Microvessel relaxation
      response to adenosine 5'-diphosphate was improved in the HCW group alone as was
      regional contractility in the ischemic territory, although myocardial fibrosis
      was decreased in both HCW and HCV. Expression of proangiogenic proteins phospho
      endothelial nitric oxide synthase and vascular endothelial growth factor was
      increased in both HCW and HCV, whereas phospho-mammalian target of rapamycin was
      increased only in the HCV group. Expression of Sirt-1 and downstream antioxidant
      phospho-FoxO1 was increased only in the HCW group. Protein oxidative stress was
      decreased in the HCW group alone, whereas capillary density was increased only in
      the HCV group. There was no significant difference in platelet function between
      groups. CONCLUSION: Moderate consumption of red wine and vodka may reduce
      cardiovascular risk by improving collateral-dependent perfusion through different
      mechanisms. Red wine may offer increased cardioprotection related to its
      antioxidant properties.

PMID- 22965996
TI  - Changes in microvascular reactivity after cardiopulmonary bypass in patients with
      poorly controlled versus controlled diabetes.
AB  - BACKGROUND: We investigated the effects of cardiopulmonary bypass (CPB) on
      peripheral arteriolar reactivity and associated signaling pathways in poorly
      controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients
      undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: Skeletal
      muscle arterioles were harvested before and after CPB from the UDM patients
      (hemoglobin A1c [HbA1c]=9.0 +/- 0.3), the CDM patients (HbA1c=6.3 +/- 0.15), and
      the ND patients (HbA1c=5.2 +/- 0.1) undergoing CABG surgery (n=10/group). In
      vitro relaxation responses of precontracted arterioles to endothelium-dependent
      vasodilators adenosine 5'-diphosphate (ADP) and substance P and the endothelium
      independent vasodilator sodium nitroprusside (SNP) were examined. The baseline
      responses to ADP, substance P, and SNP of arterioles from the UDM patients were
      decreased as compared with microvessels from the ND or CDM patients (P<0.05). The
      post-CPB relaxation responses to ADP and substance P were significantly decreased
      in all 3 groups compared with pre-CPB responses (P<0.05). However, these
      decreases were more pronounced in the UDM group (P<0.05). The post-CPB response
      to SNP was significantly decreased only in the UDM group, not in the other 2
      groups compared with pre-CPB. The expression of protein kinase C (PKC)-alpha, PKC
      beta, protein oxidation, and nitrotyrosine in the skeletal muscle were
      significantly increased in the UDM group as compared with those of ND or CDM
      groups (P<0.05). CONCLUSIONS: Poorly controlled diabetes results in impaired
      arteriolar function before and after CPB. These alterations are associated with
      the increased expression/activation of PKC-alpha and PKC-beta and enhanced
      oxidative and nitrosative stress.

PMID- 22965997
TI  - MicroRNA-145 targeted therapy reduces atherosclerosis.
AB  - BACKGROUND: MicroRNA are essential posttranscriptional modulators of gene
      expression implicated in various chronic diseases. Because microRNA-145 is highly
      expressed in vascular smooth muscle cells (VSMC) and regulates VSMC fate and
      plasticity, we hypothesized that it may be a novel regulator of atherosclerosis
      and plaque stability. METHODS AND RESULTS: Apolipoprotein E knockout mice (ApoE(
      /-)) mice were treated with either a microRNA-145 lentivirus under the control of
      the smooth muscle cell (SMC)-specific promoter SM22alpha or a SM22alpha control
      lentivirus before commencing the Western diet for 12 weeks. The SMC-targeted
      microRNA-145 treatment markedly reduced plaque size in aortic sinuses, ascending
      aortas, and brachiocephalic arteries. It also significantly increased fibrous cap
      area, reduced necrotic core area, and increased plaque collagen content. Cellular
      plaque composition analyses revealed significantly less macrophages in ApoE(-/-)
      mice treated with the SMC-specific microRNA-145. These mice also demonstrated
      marked increases in calponin levels and alpha-smooth muscle actin-positive SMC
      areas in their atherosclerotic lesions. Furthermore, lentiviral delivery of
      microRNA-145 resulted in reduced KLF4 and elevated myocardin expression in aortas
      from ApoE(-/-) mice, consistent with an effect of microRNA-145 to promote a
      contractile phenotype in VSMC. CONCLUSIONS: VSMC-specific overexpression of
      microRNA-145 is a novel in vivo therapeutic target to limit atherosclerotic
      plaque morphology and cellular composition, shifting the balance toward plaque
      stability vs plaque rupture.

PMID- 22965998
TI  - Pre-explant stability of unloading-promoted cardiac improvement predicts outcome
      after weaning from ventricular assist devices.
AB  - BACKGROUND: Detection of cardiac recovery that allows long-term cardiac stability
      after ventricular assist device (VAD) explantation is a major goal. After
      normalization of ventricular diameters during unloading, the pre-explant left
      ventricular ejection fraction (LVEF) allows the detection of patients with the
      potential to remain stable after VAD explantation. However, some patients with
      LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We
      aimed to find out if unstable improvement can be recognized before VAD
      explantation. METHODS AND RESULTS: Among 96 patients weaned from VADs since 1995,
      a relatively homogenous group of 53 patients with nonischemic chronic
      cardiomyopathy (CCM) was selected for the study. The pre-explant stability of
      major parameters of LV function, size, and geometry that were measured by
      echocardiography during serial "off-pump" trials was tested for relationship with
      cardiac stability after VAD explantation. LVEF, systolic peak wall motion
      velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall
      thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were
      selected for evaluation. In postweaning unstable patients, the selected
      parameters showed relevant instability already before VAD explantation during the
      time period between best cardiac improvement and VAD explantation and also during
      the final off-pump trial just before VAD explantation. For all parameters, there
      were significant differences (P<0.05) in pre-explant changes between patients
      with and without postweaning cardiac stability. Using the optimal cutoff values
      obtained from receiver-operating characteristic analysis, we found for our
      selected parameters predictive values for postexplant cardiac stability of >=1
      year, >=3 years, and >=5 years, ranging between 94 and 100, 92, and 100, and 78
      and 100, respectively. Using for all parameter changes the cutoff value of 10, we
      found similar predictive values for cardiac stability of >=1 year, >=3 years, and
      >=5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively.
      CONCLUSIONS: Our results strongly suggest the possibility to improve the
      prediction of postexplant transplant/VAD-free outcome in CCM patients with
      cardiac improvement during VAD support by analyzing the pre-explant stability of
      several LV off-pump echocardiographic parameters during serial off-pump trials.

PMID- 22965999
TI  - Acute aortic intramural hematoma: an analysis from the International Registry of
      Acute Aortic Dissection.
AB  - BACKGROUND: Acute aortic intramural hematoma (IMH) is an important subgroup of
      aortic dissection, and controversy surrounds appropriate management. METHODS AND
      RESULTS: Patients with acute aortic syndromes in the International Registry of
      Acute Aortic Dissection (1996-2011) were evaluated to examine differences between
      patients (based on the initial imaging test) with IMH or classic dissection (AD).
      Of 2830 patients, 178 had IMH (64 type A [42%], 90 type B [58%], and 24 arch).
      Patients with IMH were older and presented with similar symptoms, such as severe
      pain. Patients with type A IMH were less likely to present with aortic
      regurgitation or pulse deficits and were more likely to have periaortic hematoma
      and pericardial effusion. Although type A IMH and AD were managed medically
      infrequently, type B IMH were more frequently treated medically. Overall in
      hospital mortality was not statistically different for type A IMH compared to AD
      (26.6% versus 26.5%; P=0.998); type A IMH managed medically had significant
      mortality (40.0%), although less than classic AD (61.8%; P=0.195). Patients with
      type B IMH had a hospital mortality that was less but did not differ
      significantly (4.4% versus 11.1%; P=0.062) from classic AD. One-year mortality
      was not significantly different between AD and IMH. CONCLUSIONS: Acute IMH has
      similar presentation to classic AD but is more frequently complicated with
      pericardial effusions and periaortic hematoma. Patients with IMH have a mortality
      that does not differ statistically from those with classic AD. A small subgroup
      of type A IMH patients are managed medically and have a significant in-hospital
      mortality.

PMID- 22966000
TI  - Impact of controlled pericardial drainage on critical cardiac tamponade with
      acute type A aortic dissection.
AB  - BACKGROUND: Cardiac tamponade is associated with fatal outcomes for patients with
      acute type A aortic dissection, and the presence of cardiac tamponade should
      prompt urgent aortic repair. However, treatment of the patient with critical
      cardiac tamponade who cannot survive until surgery remains unclear. We analyzed
      our experience of controlled pericardial drainage (CPD) managing critical cardiac
      tamponade. METHODS AND RESULTS: Between September 2003 and May 2011, 175 patients
      with acute type A aortic dissection were treated surgically, including 43 (24.6%)
      who presented with cardiac tamponade on arrival. Eighteen patients, who did not
      respond to intravenous volume resuscitation, underwent CPD in the emergency
      department. An 8F pigtail drainage catheter was inserted percutaneously, and
      drainage volume was controlled by means of several cycles of intermittent
      drainage to maintain blood pressure at ~90 mm Hg. After CPD, all of the patients
      were transferred to the operating room, and immediate aortic repair was
      performed. Systolic blood pressure before CPD was 64.3 +/- 8.2 mm Hg and elevated
      significantly in all of the cases after CPD. Systolic blood pressure after CPD
      was 94.8 +/- 10.5 mm Hg, and increase in systolic pressure was 30.5 +/- 11.7 mm
      Hg. Total volume of aspirated pericardial effusion was 40.1 +/- 30.6 mL, and 10
      patients required only <=30-mL aspiration volume. All of the patients underwent
      aortic repair successfully. In-hospital mortality was 16.7%; however, there was
      no complications or mortality related to CPD. CONCLUSIONS: Preoperative
      pericardial drainage with control of volume is a safe and effective procedure for
      acute type A aortic dissection complicated by critical cardiac tamponade. In our
      patient population, timely controlled pericardial drainage is warranted.

PMID- 22966001
TI  - Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not
      mucosa-generated induced Foxp3+ T reg cells.
AB  - Foxp3 activity is essential for the normal function of the immune system. Two
      types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg
      (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells. These
      cell types have complementary functions. Until now, it has not been possible to
      distinguish iT reg from nT reg cells in vivo based solely on surface markers. We
      report here that Neuropilin 1 (Nrp1) is expressed at high levels by most nT reg
      cells; in contrast, mucosa-generated iT reg and other noninflammatory iT reg
      cells express low levels of Nrp1. We found that Nrp1 expression is under the
      control of TGF-beta. By tracing nT reg and iT reg cells, we could establish that
      some tumors have a very large proportion of infiltrating iT reg cells. iT reg
      cells obtained from highly inflammatory environments, such as the spinal cords of
      mice with spontaneous autoimmune encephalomyelitis (EAE) and the lungs of mice
      with chronic asthma, express Nrp1. In the same animals, iT reg cells in secondary
      lymphoid organs remain Nrp1(low). We also determined that, in spontaneous EAE, iT
      reg cells help to establish a chronic phase of the disease.

PMID- 22966002
TI  - Extrafollicular B cell activation by marginal zone dendritic cells drives T cell
      dependent antibody responses.
AB  - Dendritic cells (DCs) are best known for their ability to activate naive T cells,
      and emerging evidence suggests that distinct DC subsets induce specialized T cell
      responses. However, little is known concerning the role of DC subsets in the
      initiation of B cell responses. We report that antigen (Ag) delivery to DC
      inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)-associated CD8alpha(-)
      DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell
      dependent (TD) Ag. DCIR2(+) DCs induced rapid up-regulation of multiple B cell
      activation markers and changes in chemokine receptor expression, resulting in
      accumulation of Ag-specific B cells within extrafollicular splenic bridging
      channels as early as 24 h after immunization. Ag-specific B cells primed by
      DCIR2(+) DCs were remarkably efficient at driving naive CD4 T cell proliferation,
      yet DCIR2-induced responses failed to form germinal centers or undergo affinity
      maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were
      included at the time of immunization. These results demonstrate DCIR2(+) DCs have
      a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus
      define a novel division of labor among splenic DC subsets for B cell activation
      during humoral immune responses.

PMID- 22966003
TI  - Neuropilin-1 distinguishes natural and inducible regulatory T cells among
      regulatory T cell subsets in vivo.
AB  - Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role
      in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells
      either arise in thymus and are called natural T reg (nT reg) cells or are
      generated in the periphery through induction of Foxp3 and are called inducible T
      reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells
      in peripheral tolerance remain unclear as a result of an inability to separate
      these two subsets of T reg cells. Using a combination of novel TCR transgenic
      mice with a defined self-antigen specificity and conventional mouse models, we
      demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at
      high levels on nT reg cells and can be used to separate nT reg versus iT reg
      cells in certain physiological settings. In addition, iT reg cells generated
      through antigen delivery or converted under homeostatic conditions lack Nrp-1
      expression. Nrp-1(lo) iT reg cells show similar suppressive activity to nT reg
      cells in controlling ongoing autoimmune responses under homeostatic conditions.
      In contrast, their activity might be compromised in certain lymphopenic settings.
      Collectively, our data show that Nrp-1 provides an excellent marker to
      distinguish distinct T reg subsets and will be useful in studying the role of nT
      reg versus iT reg cells in different disease settings.

PMID- 22966005
TI  - Effects of combined drought and heavy metal stresses on xylem structure and
      hydraulic conductivity in red maple (Acer rubrum L.).
AB  - The effects of heavy metal stress, drought stress, and their combination on xylem
      structure in red maple (Acer rubrum) seedlings were investigated in an outdoor
      pot experiment. As metal-contaminated substrate, a mixture of 1.5% slag with sand
      was used, with Ni, Cu, Co, and Cr as the main contaminants. Plants grown on
      contaminated substrate had increased leaf metal concentrations. The two stresses
      reduced plant growth in an additive manner. The effects of metal and drought
      stresses on xylem characteristics were similar to each other, with a reduced
      proportion of xylem tissue, reduced conduit density in stems, and reduced conduit
      size in the roots. This resulted, in both stems and roots, in reductions in
      hydraulic conductance, xylem-specific conductivity, and leaf-specific
      conductivity. The similarity of the responses to the two stresses suggests that
      the plants' response to metals was actually a drought response, probably due to
      the reduced water uptake capacity of the metal-exposed roots. The only plant
      responses specific to metal stress were decreasing trends of stomatal density and
      chlorophyll content. In conclusion, the exposure to metals aggravates water
      stress in an additive manner, making the plants more vulnerable to drought.

PMID- 22966004
TI  - Schistosome-derived omega-1 drives Th2 polarization by suppressing protein
      synthesis following internalization by the mannose receptor.
AB  - Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni
      eggs and abundantly present in soluble egg antigen, has recently been shown to
      condition dendritic cells (DCs) to prime Th2 responses. However, the molecular
      mechanisms underlying this effect remain unknown. We show in this study by site
      directed mutagenesis of omega-1 that both the glycosylation and the RNase
      activity are essential to condition DCs for Th2 polarization. Mechanistically, we
      demonstrate that omega-1 is bound and internalized via its glycans by the mannose
      receptor (MR) and subsequently impairs protein synthesis by degrading both
      ribosomal and messenger RNA. These experiments reveal an unrecognized pathway
      involving MR and interference with protein synthesis that conditions DCs for Th2
      priming.

PMID- 22966007
TI  - Phenotyping the microcirculation with contrast-enhanced ultrasound.

PMID- 22966006
TI  - Role of the transcription factor erythroblastosis virus E26 oncogen homolog-1
      (ETS-1) as mediator of the renal proinflammatory and profibrotic effects of
      angiotensin II.
AB  - Angiotensin II (Ang II) plays a major role in the pathogenesis of end-organ
      injury in hypertension via its diverse hemodynamic and nonhemodynamic effects.
      Erythroblastosis virus E26 oncogen homolog-1 (ETS-1) is an important
      transcription factor recently recognized as an important mediator of cell
      proliferation, inflammation, and fibrosis. In the present studies, we tested the
      hypothesis that ETS-1 is a common mediator of the renal proinflammatory and
      profibrotic effects of Ang II. C57BL6 mice (n=6 per group) were infused with
      vehicle (control), Ang II (1.4 mg/kg per day), Ang II and an ETS-1 dominant
      negative peptide (10 mg/kg per day), or Ang II and an ETS-1 mutant peptide (10
      mg/kg per day) via osmotic minipump for 2 or 4 weeks. The infusion of Ang II
      resulted in significant increases in blood pressure and left ventricular
      hypertrophy, which were not modified by ETS-1 blockade. The administration of ETS
      1 dominant-negative peptide significantly attenuated Ang II-induced renal injury
      as assessed by urinary protein excretion, mesangial matrix expansion, and cell
      proliferation. Furthermore, ETS-1 dominant-negative peptide but not ETS-1 mutant
      peptide significantly reduced Ang II-mediated upregulation of transforming growth
      factor-beta, connective tissue growth factor, and alpha-smooth muscle actin. In
      addition, ETS-1 blockade reduced several proinflammatory effects of Ang II,
      including macrophage infiltration, nitrotyrosine expression, and NOX4 mRNA
      expression. Our studies suggest that ETS-1 is a common mediator of the
      proinflammatory and profibrotic effects of Ang II-induced hypertensive renal
      damage and may result in the development of novel strategies in the treatment and
      prevention of end-organ injury in hypertension.

PMID- 22966008
TI  - Epigenetic regulation of cell adhesion and communication by enhancer of zeste
      homolog 2 in human endothelial cells.
AB  - The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) mediates
      trimethylation of lysine 27 in histone 3, which acts as a repressive epigenetic
      mark. Ezh2 is essential for maintaining pluripotency of stem cells, but
      information on its role in differentiated cells is sparse. Whole-genome mRNA
      expression arrays identified 964 genes that were regulated by >2-fold 72 hours
      after small interfering RNA-mediated silencing of Ezh2 in human umbilical vein
      endothelial cells. Among them, genes associated with the gene ontology terms cell
      communication and cell adhesion were significantly overrepresented, suggesting a
      functional role for Ezh2 in the regulation of angiogenesis. Indeed, adhesion,
      migration, and tube formation assays revealed significantly altered angiogenic
      properties of human umbilical vein endothelial cells after silencing of Ezh2. To
      identify direct target genes of Ezh2, we performed chromatin immunoprecipitation
      experiments followed by whole-genome promoter arrays (chromatin
      immunoprecipitation-on-chip) and identified 5585 genes associated with
      trimethylation of lysine 27 in histone 3. Comparative analysis with our mRNA
      expression data identified 276 genes that met our criteria for putative Ezh2
      target genes, upregulation by >2-fold after Ezh2 silencing and association with
      trimethylation of lysine 27 in histone 3. Notably, we observed a striking
      overrepresentation of genes involved in wingless-type mouse mammary tumor virus
      integration site (WNT) signaling pathways. Epigenetic regulation of several of
      these genes by Ezh2 was specifically confirmed by polymerase chain reaction
      analysis of DNA enrichment after chromatin immunoprecipitation using an antibody
      specific for trimethylation of lysine 27 in histone 3. Combining mRNA expression
      arrays and chromatin immunoprecipitation-on-chip analysis, we identified 276 Ezh2
      target genes in endothelial cells. Ezh2-dependent repression of genes involved in
      cell adhesion and communication contributes to the regulation of angiogenesis.

PMID- 22966010
TI  - The prognostic significance of renal resistive index in essential hypertension.

PMID- 22966009
TI  - Neuropeptide Y promoter polymorphism modifies effects of a weight-loss diet on 2
      year changes of blood pressure: the preventing overweight using novel dietary
      strategies trial.
AB  - Neuropeptide Y (NPY) is implicated in the regulation of blood pressure (BP), and
      NPY pathways in the hypothalamus are sensitive to dietary fat. We evaluated the
      potential effect of a functional variant rs16147 located in the NPY gene promoter
      region on the association between 2-year diet intervention and change in multiple
      BP measures in the randomized Preventing Overweight Using Novel Dietary
      Strategies Trial. The NPY rs16147 was genotyped in 723 obese adults who were
      randomly assigned to 1 of 4 diets differing in the target percentages of energy
      derived from fat, protein, and carbohydrate. The changes of 4 BP phenotypes,
      including systolic BP, diastolic BP, pulse pressure, and mean arterial pressure,
      during 2-year diet intervention were analyzed. In the total participants and
      participants with hypertension, we observed significant and consistent
      interactions between rs16147 genotype and dietary fat intake on changes in
      multiple BP phenotypes at 2 years (all P for interactions <0.05). The risk allele
      (C allele) was associated with a greater reduction of BP phenotypes in response
      to low-fat diet, whereas an opposite genetic effect was observed in response to
      high-fat diet. In addition, the C allele was related to greater changes in 4 BP
      phenotypes in hypertensive compared with nonhypertensive participants. Our data
      suggest that NPY rs16147 may modulate the association between dietary fat intake
      and changes in BP phenotypes, and the C allele exerts a long-term beneficial
      effect on lowering BP in response to low-fat diet in obese and hypertensive
      subjects.

PMID- 22966011
TI  - The application of brachial-ankle pulse wave velocity as a clinical tool for
      cardiovascular risk assessment.

PMID- 22966012
TI  - Patterns of outpatient antihypertensive medication use during pregnancy in a
      Medicaid population.
AB  - Hypertensive disorders occur in approximately 6% to 8% of all pregnancies and are
      a significant source of maternal and fetal morbidity. Little is known about the
      range of agents routinely used in practice. We used Medicaid claims from 2000 to
      2007 to identify completed pregnancies. We included women who were Medicaid
      beneficiaries from at least 3 months prior to last menstrual period to 1 month
      postdelivery, and were successfully linked to infant records. Maternal exposure
      to antihypertensive medications was derived from Medicaid pharmacy claim files,
      and duration of exposure was assigned based on the days' supply dispensed. We
      identified 1,106,757 Medicaid patients in our cohort, of whom 48,453 (4.4%) were
      exposed to antihypertensive medications during pregnancy. The prevalence of
      antihypertensive use increased from 3.5% to 4.9% during the study period.
      Antihypertensive medication users were older than nonusers, more likely to be
      white or black, and more likely to have comorbid diabetes mellitus and renal
      disease. Overall, 1.9% of pregnant women were exposed during the first trimester,
      1.7% during the second trimester, and 3.2% during the third trimester. The range
      of antihypertensive medications to which patients were exposed was highly
      heterogeneous and frequently included agents other than methyldopa or labetalol.
      Angiotensin-converting enzyme inhibitor exposure, which is contraindicated in
      late pregnancy, occurred in 928 (4.9%) antihypertensive medication users in the
      second trimester and 383 (1.1%) in the third trimester. Antihypertensive use
      during pregnancy is relatively common and increasing. The wide range of agents
      used during pregnancy includes medications considered contraindicated during
      pregnancy.

PMID- 22966013
TI  - CFTR: an ion channel with a transporter-type energy-coupling mechanism.

PMID- 22966014
TI  - Nonintegral stoichiometry in CFTR gating revealed by a pore-lining mutation.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of
      the ATP-binding cassette (ABC) protein superfamily. Unlike most other ABC
      proteins that function as active transporters, CFTR is an ATP-gated chloride
      channel. The opening of CFTR's gate is associated with ATP-induced dimerization
      of its two nucleotide-binding domains (NBD1 and NBD2), whereas gate closure is
      facilitated by ATP hydrolysis-triggered partial separation of the NBDs. This
      generally held theme of CFTR gating-a strict coupling between the ATP hydrolysis
      cycle and the gating cycle-is put to the test by our recent finding of a short
      lived, post-hydrolytic state that can bind ATP and reenter the ATP-induced
      original open state. We accidentally found a mutant CFTR channel that exhibits
      two distinct open conductance states, the smaller O1 state and the larger O2
      state. In the presence of ATP, the transition between the two states follows a
      preferred O1->O2 order, a telltale sign of a violation of microscopic
      reversibility, hence demanding an external energy input likely from ATP
      hydrolysis, as such preferred gating transition was abolished in a hydrolysis
      deficient mutant. Interestingly, we also observed a considerable amount of
      opening events that contain more than one O1->O2 transition, indicating that more
      than one ATP molecule may be hydrolyzed within an opening burst. We thus conclude
      a nonintegral stoichiometry between the gating cycle and ATP consumption. Our
      results lead to a six-state gating model conforming to the classical allosteric
      mechanism: both NBDs and transmembrane domains hold a certain degree of autonomy,
      whereas the conformational change in one domain will facilitate the
      conformational change in the other domain.

PMID- 22966016
TI  - Functional, genetic, and epigenetic aspects of base and nucleotide excision
      repair in colorectal carcinomas.
AB  - PURPOSE: DNA repair capacity (DRC) is a determinant not only of cancer
      development but also of individual response to therapy. Previously, altered base
      and nucleotide excision repair (BER and NER) have been described in lymphocytes
      of patients with sporadic colorectal cancer. We, for the first time, evaluate
      both excision repair capacities in human colon biopsies to study their
      participation in colorectal tumorigenesis. EXPERIMENTAL DESIGN: Seventy pairs of
      tumor and adjacent healthy tissues were analyzed for BER- and NER-specific DRC by
      a comet repair assay. Tissue pairs were further compared for expression levels of
      a panel of 25 BER and NER genes complemented by their promoter methylation
      status. RESULTS: We observed a moderate increase of NER-DRC (P = 0.019), but not
      of BER-DRC in tumors. There was a strong correlation between both tissues for all
      investigated parameters (P < 0.001). However, 4 NER (CSB, CCNH, XPA, XPD) and 4
      BER (NEIL1, APEX1, OGG1, PARP1) genes showed a 1.08- to 1.28-fold change
      difference in expression in tumors (P < 0.05). Individual gene expression levels
      did not correlate with overall DRC, and we did not detect any aberrant
      methylation of the investigated genes. CONCLUSIONS: Our complex analysis showed
      that tumor cells are not deficient in BER and NER, but rather follow patterns
      characteristic for each individual and are comparable with adjacent tissue.
      Alteration of excision repair pathways is not a pronounced event in colorectal
      carcinogenesis. This study shows the feasibility of DRC evaluation in human solid
      tissues, representing a complex marker of multigene DNA repair processes.

PMID- 22966015
TI  - Plasmin and chymotrypsin have distinct preferences for channel activating
      cleavage sites in the gamma subunit of the human epithelial sodium channel.
AB  - Proteolytic activation of the epithelial sodium channel (ENaC) involves cleavage
      of its gamma subunit in a critical region targeted by several proteases. Our aim
      was to identify cleavage sites in this region that are functionally important for
      activation of human ENaC by plasmin and chymotrypsin. Sequence alignment revealed
      a putative plasmin cleavage site in human gammaENaC (K189) that corresponds to a
      plasmin cleavage site (K194) in mouse gammaENaC. We mutated this site to alanine
      (K189A) and expressed human wild-type (wt) alphabetagammaENaC and
      alphabetagamma(K189A)ENaC in Xenopus laevis oocytes. The gamma(K189A) mutation
      reduced but did not abolish activation of ENaC whole cell currents by plasmin.
      Mutating a putative prostasin site (gamma(RKRK178AAAA)) had no effect on the
      stimulatory response to plasmin. In contrast, a double mutation
      (gamma(RKRK178AAAA;K189A)) prevented the stimulatory effect of plasmin. We
      conclude that in addition to the preferential plasmin cleavage site K189, the
      putative prostasin cleavage site RKRK178 may serve as an alternative site for
      proteolytic channel activation by plasmin. Interestingly, the double mutation
      delayed but did not abolish ENaC activation by chymotrypsin. The time-dependent
      appearance of cleavage products at the cell surface nicely correlated with the
      stimulatory effect of chymotrypsin on ENaC currents in oocytes expressing wt or
      double mutant ENaC. Delayed proteolytic activation of the double mutant channel
      with a stepwise recruitment of so-called near-silent channels was confirmed in
      single-channel recordings from outside-out patches. Mutating two phenylalanines
      (FF174) in the vicinity of the prostasin cleavage site prevented proteolytic
      activation by chymotrypsin. This indicates that chymotrypsin preferentially
      cleaves at FF174. The close proximity of FF174 to the prostasin site may explain
      why mutating the prostasin site impedes channel activation by chymotrypsin. In
      conclusion, this study supports the concept that different proteases have
      distinct preferences for certain cleavage sites in gammaENaC, which may be
      relevant for tissue-specific proteolytic ENaC activation.

PMID- 22966017
TI  - Quantitative immunofluorescence reveals the signature of active B-cell receptor
      signaling in diffuse large B-cell lymphoma.
AB  - PURPOSE: B-cell receptor (BCR)-mediated signaling is important in the
      pathogenesis of a subset of diffuse large B-cell lymphomas (DLBCL) and the BCR
      associated kinases SYK and BTK have recently emerged as potential therapeutic
      targets. We sought to identify a signature of activated BCR signaling in DLBCL to
      aid the identification of tumors that may be most likely to respond to BCR
      pathway inhibition. EXPERIMENTAL DESIGN: We applied quantitative
      immunofluorescence (qIF) using antibodies to phosphorylated forms of proximal BCR
      signaling kinases LYN, SYK, and BTK and antibody to BCR-associated transcription
      factor FOXO1 on BCR-cross-linked formalin-fixed paraffin-embedded (FFPE) DLBCL
      cell lines as a model system and on two clinical cohorts of FFPE DLBCL specimens
      (n = 154). RESULTS: A robust signature of active BCR signaling was identified and
      validated in BCR-cross-linked DLBCL cell lines and in 71/154 (46%) of the primary
      DLBCL patient specimens. Further analysis of the primary biopsy samples revealed
      increased nuclear exclusion of FOXO1 among DLBCL with qIF evidence of active BCR
      signaling compared with those without (P = 0.004). Nuclear exclusion of FOXO1 was
      also detected in a subset of DLBCL without evidence of proximal BCR signaling
      suggesting that alternative mechanisms for PI3K/AKT activation may mediate FOXO1
      subcellular localization in these cases. CONCLUSION: This study establishes the
      feasibility of detecting BCR activation in primary FFPE biopsy specimens of
      DLBCL. It lays a foundation for future dissection of signal transduction networks
      in DLBCL and provides a potential platform for evaluating individual tumors in
      patients receiving novel therapies targeting the BCR pathway.

PMID- 22966018
TI  - Personalized medicine in a phase I clinical trials program: the MD Anderson
      Cancer Center initiative.
AB  - PURPOSE: We initiated a personalized medicine program in the context of early
      clinical trials, using targeted agents matched with tumor molecular aberrations.
      Herein, we report our observations. PATIENT AND METHODS: Patients with advanced
      cancer were treated in the Clinical Center for Targeted Therapy. Molecular
      analysis was conducted in the MD Anderson Clinical Laboratory Improvement
      Amendments (CLIA)-certified laboratory. Patients whose tumors had an aberration
      were treated with matched targeted therapy, when available. Treatment assignment
      was not randomized. The clinical outcomes of patients with molecular aberrations
      treated with matched targeted therapy were compared with those of consecutive
      patients who were not treated with matched targeted therapy. RESULTS: Of 1,144
      patients analyzed, 460 (40.2%) had 1 or more aberration. In patients with 1
      molecular aberration, matched therapy (n = 175) compared with treatment without
      matching (n = 116) was associated with a higher overall response rate (27% vs.
      5%; P < 0.0001), longer time-to-treatment failure (TTF; median, 5.2 vs. 2.2
      months; P < 0.0001), and longer survival (median, 13.4 vs. 9.0 months; P =
      0.017). Matched targeted therapy was associated with longer TTF compared with
      their prior systemic therapy in patients with 1 mutation (5.2 vs. 3.1 months,
      respectively; P < 0.0001). In multivariate analysis in patients with 1 molecular
      aberration, matched therapy was an independent factor predicting response (P =
      0.001) and TTF (P = 0.0001). CONCLUSION: Keeping in mind that the study was not
      randomized and patients had diverse tumor types and a median of 5 prior
      therapies, our results suggest that identifying specific molecular abnormalities
      and choosing therapy based on these abnormalities is relevant in phase I clinical
      trials.

PMID- 22966019
TI  - Differential gene expression profile associated to apoptosis induced by
      dexamethasone in CLL cells according to IGHV/ZAP-70 status.
AB  - PURPOSE: Glucocorticoids are part of the therapeutic armamentarium of chronic
      lymphocytic leukemia (CLL) where it has been suggested that cells with unmutated
      IGHV genes exhibit higher sensitivity. The mechanisms by which glucocorticoids
      are active in CLL are not well elucidated. We aimed to ascertain the activity of
      dexamethasone in CLL cells according to prognosis and to identify the molecular
      mechanisms that are influencing the response to this drug. EXPERIMENTAL DESIGN:
      Sensitivity to dexamethasone was analyzed ex vivo in 50 CLL and compared
      according to IGHV mutational status and/or ZAP-70 expression. The response was
      further compared by gene expression profiling (GEP) of selected cases. Expression
      of genes of interest was validated by quantitative reverse transcriptase PCR.
      RESULTS: Response to dexamethasone was higher in cases with unmutated IGHV/high
      ZAP-70 expression, and the levels of induction of the pro-apoptotic Bim protein
      correlated with the degree of cell death. GEP analysis showed few genes
      differentially expressed after dexamethasone treatment between mutated and
      unmutated cases. However, functional annotation analysis showed that unmutated
      cases had significant enrichment in terms related to apoptosis. Specific analysis
      of genes of interest conducted in a large series disclosed that in unmutated IGHV
      cells, FKBP5 expression was higher at baseline and after dexamethasone exposure
      and that GILZ was more induced by dexamethasone treatment in these cases.
      CONCLUSIONS: Unmutated IGHV/high ZAP-70 CLL cells exhibit better response to
      dexamethasone treatment, which is accompanied by a differential expression of
      genes involved in the glucocorticoid receptor pathway and by an increased
      induction of genes related to apoptosis.

PMID- 22966020
TI  - Suppression of human glioma xenografts with second-generation IL13R-specific
      chimeric antigen receptor-modified T cells.
AB  - PURPOSE: Glioblastoma multiforme (GBM) remains highly incurable, with frequent
      recurrences after standard therapies of maximal surgical resection, radiation,
      and chemotherapy. To address the need for new treatments, we have undertaken a
      chimeric antigen receptor (CAR) "designer T cell" (dTc) immunotherapeutic
      strategy by exploiting interleukin (IL)13 receptor alpha-2 (IL13Ralpha2) as a GBM
      selective target. EXPERIMENTAL DESIGN: We tested a second-generation IL13
      "zetakine" CAR composed of a mutated IL13 extracellular domain linked to
      intracellular signaling elements of the CD28 costimulatory molecule and CD3zeta.
      The aim of the mutation (IL13.E13K.R109K) was to enhance selectivity of the CAR
      for recognition and killing of IL13Ralpha2(+) GBMs while sparing normal cells
      bearing the composite IL13Ralpha1/IL4Ralpha receptor. RESULTS: Our aim was
      partially realized with improved recognition of tumor and reduced but persisting
      activity against normal tissue IL13Ralpha1(+) cells by the IL13.E13K.R109K CAR.
      We show that these IL13 dTcs were efficient in killing IL13Ralpha2(+) glioma cell
      targets with abundant secretion of cytokines IL2 and IFNgamma, and they displayed
      enhanced tumor-induced expansion versus control unmodified T cells in vitro. In
      an in vivo test with a human glioma xenograft model, single intracranial
      injections of IL13 dTc into tumor sites resulted in marked increases in animal
      survivals. CONCLUSIONS: These data raise the possibility of immune targeting of
      diffusely invasive GBM cells either via dTc infusion into resection cavities to
      prevent GBM recurrence or via direct stereotactic injection of dTcs to suppress
      inoperable or recurrent tumors. Systemic administration of these IL13 dTc could
      be complicated by reaction against normal tissues expressing IL13Ra1.

PMID- 22966021
TI  - Decline in gastroenteritis-related triage calls after rotavirus vaccine
      licensure.
AB  - OBJECTIVE: We sought to determine the impact of rotavirus vaccine implementation
      on gastroenteritis (GE)-related calls to a large telephone triage service in
      Tennessee. METHODS: Total and GE-related calls received by the Vanderbilt
      Telephone Triage Program for children <5 years of age were examined from May 1,
      2004 to April 30, 2010. Time series adapted Poisson regression models were used
      to compare weekly GE-related call proportions between the prevaccine (May 2004 to
      April 2007) and postlicensure (May 2007 to April 2010) periods. Separate models
      compared GE-related call proportions in the historical rotavirus (February to
      April) and nonrotavirus (May to January) seasons. Associations between call data
      and laboratory-confirmed rotavirus detections and regionally reported norovirus
      activity were also assessed. RESULTS: There were 156362 total calls and 19731 GE
      related calls. Annual GE-related call proportions declined by 8% (95% confidence
      interval, 3%-12%) in the postlicensure period; declines ranging from 23% to 31%
      occurred during the historical rotavirus season in all 3 postlicensure years. No
      declines occurred in the nonrotavirus season. After vaccine licensure, reductions
      in laboratory-confirmed rotavirus activity were associated with declines in GE
      related call proportions. Peak GE-related call proportions in the postlicensure
      period occurred earlier than in prevaccine years and were not strongly associated
      with laboratory-confirmed rotavirus but instead showed good correlation with
      norovirus outbreaks. CONCLUSIONS: A decline in GE-related call proportions among
      young children after rotavirus vaccine licensure was documented by using a novel
      surveillance platform that captures mild GE not detected in other surveillance
      systems. Since rotavirus vaccine licensure, peak call proportions correlate with
      regional norovirus activity, highlighting the role of that pathogen in community
      GE.

PMID- 22966022
TI  - Trends of transcutaneous bilirubin in neonates who develop significant
      hyperbilirubinemia.
AB  - OBJECTIVES: To provide data on the natural course of transcutaneous bilirubin
      (TcB) levels in neonates before the development of significant
      hyperbilirubinemia, and to assess the effect of different demographic and
      perinatal factors on the rate of TcB increase. METHODS: We analyzed 2454 TcB
      measurements from 419 neonates before the development of significant
      hyperbilirubinemia. Mean TcB values and TcB percentiles for designated times were
      calculated, and the effect of different risk factors on the rate of TcB increase
      was assessed. TcB percentile curves were plotted for comparison on a population
      based TcB nomogram. RESULTS: Blood incompatibilities and glucose-6-phosphate dehy
      drogenase deficiency were associated with higher rates of TcB in-crease during
      the first 36 to 48 postnatal hours, whereas smaller gestational age, increased
      weight loss, and exclusive breastfeeding had a similar but later effect. Compared
      with general population norms, a different pattern of TcB increase was noted in
      neonates who developed significant hyperbilirubinemia, but with a sub-stantial
      overlap of TcB values during the first 24 to 48 postnatal hours. CONCLUSIONS: We
      provide data on the natural course of TcB levels before the development of
      significant hyperbilirubinemia in a white population of term and near-term
      neonates. Smaller gestational age, blood incompatibilities, glucose-6-phosphate
      dehydrogenase deficiency, increased weight loss, and exclusive breastfeeding
      significantly affected the rate of TcB increase in a time-dependent manner. These
      findings may assist in assessing the risk for significant hyperbilirubinemia and
      planning appropriate follow-up strategies for neonates with borderline bilirubin
      levels.

PMID- 22966023
TI  - Impact of maternal depressive symptoms on growth of preschool- and school-aged
      children.
AB  - OBJECTIVE: The aim of our study was to examine whether maternal depressive
      symptoms at 9 months postpartum adversely affect growth in preschool- and school
      aged children. METHODS: We used data from the US nationally representative Early
      Childhood Longitudinal Study, Birth Cohort. We fit multivariable logistic
      regression models to study maternal depressive symptoms at 9 months postpartum
      (using the Center for Epidemiologic Studies Depression Scale) in relation to
      child growth outcomes, <= 10% height-for-age, <= 10% weight-for-height, and <=
      10% weight-for-age at 4 and 5 years. RESULTS: At 9 months, 24% of mothers
      reported mild depressive symptoms and 17% moderate/severe symptoms. After
      adjustment for household, maternal, and child factors, children of mothers with
      moderate to severe levels of depressive symptoms at 9 months' postpartum had a
      40% increased odds of being <= 10% in height-for-age at age 4 (odds ratio = 1.40,
      95% confidence interval: 1.04-1.89) and 48% increased odds of being <= 10% in
      height-for-age at age 5 (odds ratio = 1.48, 95% confidence interval: 1.03-2.13)
      compared with children of women with few or no depressive symptoms. There was no
      statistically significant association between maternal depressive symptoms and
      children being <= 1 0% in weight-for-height and weight-for-age at 4 or 5 years.
      CONCLUSIONS: Maternal depressive symptoms during infancy may affect physical
      growth in early childhood. Prevention, early detection, and treatment of maternal
      depressive symptoms during the first year postpartum may prevent childhood height
      for-age <= 10th percentile among preschool- and school-aged children.

PMID- 22966025
TI  - Incidence of chronic bilirubin encephalopathy in Canada, 2007-2008.
AB  - BACKGROUND AND OBJECTIVES: Despite the implementation of screening guidelines to
      identify infants at risk for hyperbilirubinemia, chronic bilirubin encephalopathy
      (CBE) continues to be reported worldwide in otherwise healthy infants. The
      incidence of CBE in Canada is unknown. The objectives of this study were to
      establish the incidence of CBE in Canada and identify epidemiological and medical
      risk factors associated with its occurrence. METHODS: Data on infants were
      collected prospectively through the Canadian Pediatric Surveillance Program.
      Infants born between January 1, 2007 and December 31, 2008 were included if they
      either had symptoms of CBE and a history of hyperbilirubinemia, or if they
      presented in the newborn period with severe hyperbilirubinemia and an abnormal
      MRI finding as per the reporting physician. RESULTS: During the study period, 20
      cases were identified; follow-up data were available for 14 of these. The causes
      for the hyperbilirubinemia included glucose-6-phosphate dehydrogenase deficiency
      (n = 5), sepsis (n = 2), ABO incompatibility and other red blood cell antibodies
      (n = 7). Fifteen infants had abnormal brain MRI findings during the neonatal
      period. At follow-up, 5 infants developed classic choreoathetoid cerebral palsy,
      6 had spectrum of neurologic dysfunction and developmental delay (as described by
      the reporting physician), and 3 were healthy. CONCLUSIONS: CBE continues to occur
      in Canada at an incidence that appears to be higher than previously reported.

PMID- 22966024
TI  - Self-reported energy intake by age in overweight and healthy-weight children in
      NHANES, 2001-2008.
AB  - OBJECTIVE: Variation in energy intake by weight status at different ages may
      explain inconsistencies in previous research on energy intake and obesity.
      Therefore, our objective was to determine the relationship between reported daily
      energy intake and categorized weight status across childhood. METHODS: We
      examined dietary reports of children ages 1 to 17 years by using the National
      Health and Nutrition Examination Survey, 2001-2008 (N = 12648). Using measured
      height and weight, we categorized weight status based on weight-for-length
      percentile (age <2 years) or BMI percentile (ages 2-17 years) using current
      recommendations. Dietary intake was reported by using the repeatedly validated
      automated multiple pass method, a detailed 2-day 24-hour recall. We used ordinary
      least squares regression to examine the interactions of age and weight category
      on total energy intake, controlling for gender, race, ethnicity, and income.
      RESULTS: Weight status and age both have positive associations with self-reported
      energy intake. However, the interaction between weight and age demonstrates a
      negative effect throughout childhood, such that young obese/overweight children
      reported consuming significantly more calories and obese/overweight adolescents
      reported consuming fewer calories than their same-age healthy-weight peers.
      CONCLUSIONS: In a nationally representative cross-sectional sample, overweight
      and obese girls older than 7 years and boys older than 10 years reported
      consuming fewer daily calories than their healthy-weight peers. One explanation
      for this would be that increased energy intake in early childhood is related to
      the onset of obesity, but other mechanisms, such as differences in energy
      expenditure, may contribute more to maintaining obese/overweight status through
      adolescence.

PMID- 22966026
TI  - Pediatric residency training director tobacco survey II.
AB  - OBJECTIVE: To assess the current status of pediatric residency training on
      tobacco use and smoke exposure. METHODS: A nationwide survey of all pediatric
      residency training directors in the United States was conducted from November
      2010 to May 2011 via use of surveymonkey.com. The survey assessed training
      director characteristics, attitudes and beliefs about pediatricians' role in
      addressing tobacco control in patients and parents, past training in tobacco use
      and smoke exposure, inclusion of tobacco control in their training curriculum,
      and barriers to inclusion. Data are presented as percentages, with chi(2) tests
      of significance. RESULTS: Sixty-five percent of programs included tobacco control
      in the curriculum, and training directors who received past training in tobacco
      prevention and control were significantly more likely to include tobacco use and
      smoke exposure than those without training. The vast majority of training
      programs focused on health effects as opposed to intervention, failed to employ
      active learning to teach tobacco intervention skills, did not evaluate resident
      tobacco knowledge and skills, and did not encourage use of medications to help
      parents quit smoking. CONCLUSIONS: Pediatric residency training programs must do
      more to prepare residents to address tobacco use and smoke exposure. Given the
      many competing priorities of residency training, there is a need to explore new
      ways of integrating tobacco control into the 3-year curriculum.

PMID- 22966027
TI  - Views of adolescents and parents on pediatric research without the potential for
      clinical benefit.
AB  - OBJECTIVE: Critics argue that pediatric research without the potential for
      clinical benefit is unethical because it treats children as mere means, exposing
      those who cannot consent to risks for the benefit of others. The present survey
      was designed to assess whether this claim is consistent with the views of
      adolescents who actually participate in research, or their parents. METHODS:
      Interviews were conducted with adolescents participating in research at the NIH
      Clinical Center or Seattle Children's Hospital, and their parents, from June 2008
      through April 2010. RESULTS: Interviews were completed with 177 of 186
      adolescent/parent pairs (response rate= 95.2%). Overall, 90% of the adolescents
      and parents were willing to have the adolescent undergo a few extra blood draws,
      and 65% were willing to have the adolescent undergo an extra skin biopsy, for
      research purposes. The vast majority felt that the adolescents were making an
      important contribution to help others, and 80.8% of the adolescents felt proud to
      be doing so. Respondents overall were equally willing to have the adolescent face
      risks to help others in a research study or in a charitable activity.
      CONCLUSIONS: The views and experiences of these respondents do not support the
      claim that pediatric research without the potential for clinical benefit treats
      subjects as mere means. Instead, the findings provide proof of principle for the
      claim that non-beneficial pediatric research involves a type of charitable
      activity which offers children the opportunity to contribute to a valuable
      project to help others.

PMID- 22966028
TI  - Beliefs and expectations of Canadian parents who bring febrile children for
      medical care.
AB  - OBJECTIVES: The purpose of this survey was to study the beliefs, expectations,
      and satisfaction of Canadian parents regarding fever and the treatment of their
      febrile children. METHODS: A survey was developed exploring caregiver beliefs and
      treatment strategies, as well as expectations and satisfaction with medical care.
      Some items were modeled after previous studies to allow comparison. Caregivers
      with febrile children were recruited from 2005 to 2007 at 3 urgent care centers
      and emergency departments in Edmonton, Canada: a pediatric emergency department
      (n = 376), an urban urgent care center (n = 227), and a suburban urgent care
      clinic (n = 173). RESULTS: High and rapidly rising temperature, as well as
      physical symptoms associated with fever, caused concern in most parents surveyed.
      Seventy-four percent of parents felt that the elevated temperature from fever was
      dangerous and 90.3% always try to treat it. Forty degrees Celsius was the most
      commonly sited threshold for danger. Identifying the cause (80.6%) and
      seriousness (87.4%) of fever were the most com-mon stressors identified.
      Caregivers expected to receive information about the child's illness and
      appropriate treatment. The parents most often wanted information about febrile
      seizures and the potential dangers of febrile illness. Only 16.7% of caregivers
      expected anti-biotics. Nearly 92% of subjects were usually satisfied with medical
      care. CONCLUSIONS: Fever phobia continues to be a significant issue for Canadian
      parents. As a result, they treat fever aggressively and often seek medical
      attention. Good communication is important for medical staff caring for febrile
      children and typically leads to satisfied parents.

PMID- 22966029
TI  - Resident work hour changes in children's hospitals: impact on staffing patterns
      and workforce needs.
AB  - BACKGROUND AND OBJECTIVE: Changes to the structure and nature of resident duty
      hour assignments can create compensatory workforce needs in hospital or
      outpatient settings to ensure appropriate patient care. The objective of this
      study was to understand what, if any, adjustments children's hospitals have made
      in staffing and assignments of specific duties during the past 2 years as a
      result of residency duty hour changes, and what changes are anticipated in the
      upcoming 2 years. METHODS: Mail survey to chief executive officers and chief
      operating officers of 114 freestanding children's hospitals or children's
      hospitals within a larger hospital. RESULTS: Response rate was 65.4%. Respondents
      from more than half of hospitals (57%, N = 36) reported increasing the overall
      full-time equivalent (FTE) of hospitalists in response to the 2011 resident work
      hour changes. Forty-eight percent (N = 30) increased the overall FTE of pediatric
      nurse practitioners (PNPs), and 42% (N = 27) increased the FTE of neonatal nurse
      practitioners (NNPs). Most hospitals plan to increase the number of hospitalists
      (69%, N = 44), PNPs (59%, N = 37), or pediatric attending physicians (56%, N =
      35) over the next 2 years. Forty-three percent (N = 27) of hospitals plan to
      increase the number of NNPs over the next 2 years, and a quarter plan to increase
      physician assistants (25%, N = 16) or pediatric house staff (24%, N = 15).
      CONCLUSIONS: Changes in work hours for pediatric residents appear to have an
      impact on workforce planning within pediatric hospitals. Decreases in available
      resident work hours will create an increasing demand, primarily for nonresident
      physicians, PNPs, and NNPs.

PMID- 22966030
TI  - Blood alcohol levels for American Indian mothers and newborns.
AB  - Very little is known about the alcohol elimination rates of newborns who have had
      chronic alcohol exposure in utero. In these case reports, blood alcohol levels
      were taken immediately before delivery, at delivery, and postdelivery for 2
      mothers who drank alcohol during their pregnancies and 3 single-birth newborns.
      Newborn A1 of Mother A had no physical characteristics of fetal alcohol syndrome
      (FAS). The initial blood alcohol level for this newborn was 38.4 mg/dL 129
      minutes after birth, with a subsequent blood alcohol level of 5.5 mg/dL 304
      minutes after delivery, resulting in an alcohol elimination rate of 11.3 mg/dL
      per hour. The blood alcohol level for Mother A was 87.4 mg/dL 66 minutes before
      delivery. Newborn A2 of mother A had FAS. Sixty minutes after delivery, the blood
      alcohol level for this newborn was 39.5 mg/dL, and the alcohol level of the
      mother was 42.1 mg/dL. Newborn B1 of mother B had FAS. At 67 minutes after birth,
      newborn B1 had a blood alcohol level of 246.5 mg/dL, which dropped to 178.7 mg/dL
      302 minutes after birth, resulting in an alcohol elimination rate of 17.3 mg/dL
      per hour. This alcohol elimination rate is within the metabolism range (15-49
      mg/dL per hour) of adults with alcoholism. The maternal blood alcohol level was
      265.9 mg/dL 27 minutes before delivery. Blood alcohol levels drawn on both the
      mother and newborn at delivery and 2 or 3 hourly follow-up levels can provide
      evidence that fetal alcohol dehydrogenase activity is induced by chronic maternal
      alcohol use.

PMID- 22966032
TI  - Recommendations for prevention and control of influenza in children, 2012-2013.
AB  - The purpose of this statement is to update recommendations for routine use of
      trivalent seasonal influenza vaccine and antiviral medications for the prevention
      and treatment of influenza in children. The key points for the upcoming 2012-2013
      season are: (1) this year's trivalent influenza vaccine contains
      A/California/7/2009 (H1N1)-like antigen (derived from influenza A [H1N1] pdm09
      [pH1N1] virus); A/Victoria/361/2011 (H3N2)-like antigen; and B/Wisconsin/1/2010
      like antigen (the influenza A [H3N2] and B antigens differ from those contained
      in the 2010-2011 and 2011-2012 seasonal vaccines); (2) annual universal influenza
      immunization is indicated; and (3) an updated dosing algorithm for administration
      of influenza vaccine to children 6 months through 8 years of age has been
      created. Pediatricians, nurses, and all health care personnel should promote
      influenza vaccine use and infection control measures. In addition, pediatricians
      should promptly identify influenza infections to enable rapid treatment, when
      indicated, to reduce morbidity and mortality.

PMID- 22966031
TI  - Comparison of mortality and morbidity of very low birth weight infants between
      Canada and Japan.
AB  - OBJECTIVE: To compare neonatal outcomes of very low birth weight (VLBW) infants
      admitted to NICUs participating in the Canadian Neonatal Network and the Neonatal
      Research Network of Japan. METHODS: Secondary analyses of VLBW infants in both
      national databases between 2006 and 2008 were conducted. The primary outcome was
      a composite of mortality or any major morbidity defined as severe neurologic
      injury, bronchopulmonary dysplasia, necrotizing enterocolitis, or severe
      retinopathy of prematurity at discharge. Secondary outcomes included individual
      components of primary outcome and late-onset sepsis. Logistic regression
      adjusting for confounders was performed. RESULTS: A total of 5341 infants from
      the Canadian Neonatal Network and 9812 infants from the Neonatal Research Network
      of Japan were compared. There were higher rates of maternal hypertension,
      diabetes mellitus, outborn, prenatal steroid use, and multiples in Canada,
      whereas cesarean deliveries were higher in Japan. Composite primary outcome was
      better in Japan in comparison with Canada (adjusted odds ratio [AOR] 0.87, 95%
      confidence interval [CI] 0.79-0.96). The odds of mortality (AOR 0.40, 95% CI 0.34
      0.47), severe neurologic injury (AOR 0.57, 95% CI 0.49-0.66), necrotizing
      enterocolitis (AOR 0.23, 95% CI 0.19-0.29), and late-onset sepsis (AOR 0.22, 95%
      CI 0.19-0.25) were lower in Japan; however, the odds of bronchopulmonary
      dysplasia (AOR 1.24, 95% CI 1.10-1.42) and severe retinopathy of prematurity (AOR
      1.98, 95%CI 1.69-2.33) were higher in Japan. CONCLUSIONS: Composite outcome of
      mortality or major morbidity was significantly lower in Japan than Canada for
      VLBW infants. However, there were significant differences in various individual
      outcomes identifying areas for improvement for both networks.

PMID- 22966033
TI  - Acute bacterial osteoarticular infections: eight-year analysis of C-reactive
      protein for oral step-down therapy.
AB  - BACKGROUND: One of the most important decisions in the treatment of
      osteoarticular infections is the time at which parenteral therapy can be changed
      to oral therapy. C-reactive protein (CRP) is an acute inflammatory indicator with
      a half-life of 19 hours and thus can be helpful in assessing the adequacy of
      therapy for bacterial infections. At our institution, a combination of CRP and
      clinical findings is used to determine the transition to oral therapy. METHODS: A
      search of 8 years of electronic records identified children with osteoarticular
      infections. Only children with culture-positive acute bacterial arthritis (ABA)
      or acute bacterial osteomyelitis (ABO) were studied further. A primary chart
      review of demographic and clinical data was conducted, and a secondary chart
      review of complicated outcomes was performed. RESULTS: Of 194 total patients,
      complicated outcomes occurred in 40, of which 35 were prolonged therapy. Only 1
      microbiologic failure occurred, presumably due to a retained intra-articular
      fragment of infected bone. CRP was highest initially among patients with
      simultaneous ABO + ABA and among those with complicated outcomes, and was lower
      at the transition to oral therapy in the complicated outcome group (1.5 vs 2.1
      mg/dL; P = .012). CONCLUSIONS: The combination of clinical findings and CRP is a
      useful tool to transition children with osteoarticular infections to oral
      therapy. Complicated outcomes were associated with higher early CRP at diagnosis
      and lower CRP at the end of parenteral therapy, suggesting that clinicians were
      more conservative with prolonged initial parenteral therapy in this group.

PMID- 22966034
TI  - Five-year follow-up of harms and benefits of behavioral infant sleep
      intervention: randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Randomized trials have demonstrated the short- to
      medium-term effectiveness of behavioral infant sleep interventions. However,
      concerns persist that they may harm children's emotional development and
      subsequent mental health. This study aimed to determine long-term harms and/or
      benefits of an infant behavioral sleep program at age 6 years on (1) child, (2)
      child-parent, and (3) maternal outcomes. METHODS: Three hundred twenty-six
      children (173 intervention) with parent-reported sleep problems at age 7 months
      were selected from a population sample of 692 infants recruited from well-child
      centers. The study was a 5-year follow-up of a population-based cluster
      randomized trial. Allocation was concealed and researchers (but not parents) were
      blinded to group allocation. Behavioral techniques were delivered over 1 to 3
      individual nurse consultations at infant age 8 to 10 months, versus usual care.
      The main outcomes measured were (1) child mental health, sleep, psychosocial
      functioning, stress regulation; (2) child-parent relationship; and (3) maternal
      mental health and parenting styles. RESULTS: Two hundred twenty-five families
      (69%) participated. There was no evidence of differences between intervention and
      control families for any outcome, including (1) children's emotional (P = .8) and
      conduct behavior scores (P = .6), sleep problems (9% vs 7%, P = .2), sleep habits
      score (P = .4), parent- (P = .7) and child-reported (P = .8) psychosocial
      functioning, chronic stress (29% vs 22%, P = .4); (2) child-parent closeness (P =
      .1) and conflict (P = .4), global relationship (P = .9), disinhibited attachment
      (P = .3); and (3) parent depression, anxiety, and stress scores (P = .9) or
      authoritative parenting (63% vs 59%, P = .5). CONCLUSIONS: Behavioral sleep
      techniques have no marked long-lasting effects (positive or negative). Parents
      and health professionals can confidently use these techniques to reduce the short
      to medium-term burden of infant sleep problems and maternal depression.

PMID- 22966035
TI  - Defining the phenotype in congenital disorder of glycosylation due to ALG1
      mutations.
AB  - Deficiency of beta-1,4 mannosyltransferase (MT-1) congenital disorder of
      glycosylation (CDG), due to ALG1 gene mutations. Features in 9 patients reported
      previously consisted of prenatal growth retardation, pregnancy-induced maternal
      hypertension and fetal hydrops. Four patients died before 5 years of age, and
      survivors showed a severe psychomotor retardation. We report on 7 patients with
      psychomotor delay, microcephaly, strabismus and coagulation abnormalities,
      seizures and abnormal fat distribution. Four children had a stable clinical
      course, two had visual impairment, and 1 had hearing loss. Thrombotic and
      vascular events led to deterioration of the clinical outcome in 2 patients. Four
      novel ALG1 mutations were identified. Pathogenicity was determined in alg1 yeast
      mutants transformed with hALG1. Functional analyses showed all novel mutations
      representing hypomorphs associated with residual enzyme activity. We extend the
      phenotypic spectrum including the first description of deafness in MT1
      deficiency, and report on mildly affected patients, surviving to adulthood. The
      dysmorphic features, including abnormal fat distribution and strabismus highly
      resemble CDG due to phosphomannomutase-2 deficiency (PMM2-CDG), the most common
      type of CDG. We suggest testing for ALG1 mutations in unsolved CDG patients with
      a type 1 transferrin isoelectric focusing pattern, especially with epilepsy,
      severe visual loss and hemorrhagic/thrombotic events.

PMID- 22966036
TI  - Medical errors in US pediatric inpatients with chronic conditions.
AB  - OBJECTIVE: To investigate the association between chronic conditions and
      iatrogenic medical errors in US pediatric inpatients. METHODS: The 2006 Kids'
      Inpatient Database (KID) was analyzed. Medical errors were defined by using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) codes. Medical error rates per 100 hospital discharges and per 1000
      inpatient days were calculated. Logistic regression models were fitted to study
      the association between number of chronic conditions and medical errors,
      controlling for patient characteristics, hospital characteristics, disease
      severity, and length of stay. RESULTS: In the 2006 KID, 22.3% of pediatric
      inpatients had 1 chronic condition, 9.8% had 2 chronic conditions, and 12.0% had
      >= 3 chronic conditions. The overall medical error rate per 100 discharges was
      3.0 (95% confidence interval [CI]: 2.8-3.3); it was 5.3 (95% CI: 4.9-5.7) in
      children with chronic conditions and 1.3 (95% CI: 1.2-1.3) in children without
      chronic conditions. The medical error rate per 1000 inpatient days was also
      higher in children with chronic conditions. The association between chronic
      conditions and medical errors remained statistically significant in logistic
      regression models adjusting for patient characteristics, hospital
      characteristics, disease severity, and length of stay. In the adjusted model, the
      odds ratio of medical errors for children with 1 chronic condition was 1.40 (95%
      CI: 1.32-1.48); for children with 2 conditions, the OR was 1.55 (95% CI: 1.45
      1.66); and for children with 3 conditions, the OR was 1.66 (95% CI: 1.53-1.81).
      CONCLUSIONS: The number of chronic conditions was significantly associated with
      iatrogenic medical errors in pediatric inpatients.

PMID- 22966039
TI  - Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease
      links numerous treatment rationales.
AB  - The evident limitations of the amyloid theory of the pathogenesis of Alzheimer's
      disease are increasingly putting alternatives in the spotlight. We argue here
      that a number of independently developing approaches to therapy-including
      specific and nonspecific anti-tumor necrosis factor (TNF) agents, apolipoprotein
      E mimetics, leptin, intranasal insulin, the glucagon-like peptide-1 mimetics and
      glycogen synthase kinase-3 (GSK-3) antagonists-are all part of an interlocking
      chain of events. All these approaches inform us that inflammation and thence
      cerebral insulin resistance constitute the pathway on which to focus for a
      successful clinical outcome in treating this disease. The key link in this chain
      presently absent is a recognition by Alzheimer's research community of the long
      neglected history of TNF induction of insulin resistance. When this is
      incorporated into the bigger picture, it becomes evident that the interventions
      we discuss are not competing alternatives but equally valid approaches to
      correcting different parts of the same pathway to Alzheimer's disease. These
      treatments can be expected to be at least additive, and conceivably synergistic,
      in effect. Thus the inflammation, insulin resistance, GSK-3, and mitochondrial
      dysfunction hypotheses are not opposing ideas but stages of the same fundamental,
      overarching, pathway of Alzheimer's disease pathogenesis. The insight this
      provides into progenitor cells, including those involved in adult neurogenesis,
      is a key part of this approach. This pathway also has therapeutic implications
      for other circumstances in which brain TNF is pathologically increased, such as
      stroke, traumatic brain injury, and the infectious disease encephalopathies.

PMID- 22966037
TI  - Molecular basis of electrophilic and oxidative defense: promises and perils of
      Nrf2.
AB  - Induction of drug-metabolizing enzymes through the antioxidant response element
      (ARE)-dependent transcription was initially implicated in chemoprevention against
      cancer by antioxidants. Recent progress in understanding the biology and
      mechanism of induction revealed a critical role of induction in cellular defense
      against electrophilic and oxidative stress. Induction is mediated through a novel
      signaling pathway via two regulatory proteins, the nuclear factor erythroid 2
      related factor 2 (Nrf2) and the Kelch-like erythroid cell-derived protein with
      CNC homology-associated protein 1 (Keap1). Nrf2 binds to Keap1 at a two site
      binding interface and is ubiquitinated by the Keap1/cullin 3/ring box protein-1
      ubiquitin ligase, resulting in a rapid turnover of Nrf2 protein. Electrophiles
      and oxidants modify critical cysteine thiols of Keap1 and Nrf2 to inhibit Nrf2
      ubiquitination, leading to Nrf2 activation and induction. Induction increases
      stress resistance critical for cell survival, because knockout of Nrf2 in mice
      increased susceptibility to a variety of toxicity and disease processes.
      Collateral to diverse functions of Nrf2, genome-wide search has led to the
      identification of a plethora of ARE-dependent genes regulated by Nrf2 in an
      inducer-, tissue-, and disease-dependent manner to control drug metabolism,
      antioxidant defense, stress response, proteasomal degradation, and cell
      proliferation. The protective nature of Nrf2 could also be hijacked in a number
      of pathological conditions by means of somatic mutation, epigenetic alteration,
      and accumulation of disruptor proteins, promoting drug resistance in cancer and
      pathologic liver features in autophagy deficiency. The repertoire of ARE inducers
      has expanded enormously; the therapeutic potential of the inducers has been
      examined beyond cancer prevention. Developing potent and specific ARE inducers
      and Nrf2 inhibitors holds certain new promise for the prevention and therapy
      against cancer, chronic disease, and toxicity.

PMID- 22966040
TI  - Global effect of interleukin-10 on the transcriptional profile induced by
      Neisseria meningitidis in human monocytes.
AB  - In meningococcal septic shock, the dominant inducer of inflammation is
      lipopolysaccharide (LPS) in the outer membrane of Neisseria meningitidis, while
      interleukin-10 (IL-10) is the principal anti-inflammatory cytokine. We have used
      microarrays and Ingenuity Pathway Analysis to study the global effects of IL-10
      on gene expression induced by N. meningitidis, after exposure of human monocytes
      (n = 5) for 3 h to N. meningitidis (10(6) cells/ml), recombinant human IL-10
      (rhIL-10) (25 ng/ml), and N. meningitidis combined with rhIL-10. N. meningitidis
      and IL-10 differentially expressed 3,579 and 648 genes, respectively. IL-10
      downregulated 125 genes which were upregulated by N. meningitidis, including
      NLRP3, the key molecule of the NLRP3 inflammasome. IL-10 also upregulated 270
      genes which were downregulated by N. meningitidis, including members of the
      leukocyte immunuglobulin-like receptor (LIR) family. Fifty-three genes revealed a
      synergistically increased expression when N. meningitidis and IL-10 were
      combined. AIM2 (the principal molecule of the AIM2 inflammasome) was among these
      genes (fold change [FC], 18.3 versus 7.4 and 9.4 after stimulation by N.
      meningitidis and IL-10, respectively). We detected reduced concentrations (92% to
      40%) of six cytokines (IL-1b, IL-6, IL-8, tumor necrosis factor alpha [TNF
      alpha], macrophage inflammatory protein alpha [MIP-alpha], MIP-beta) in the
      presence of IL-10, compared with concentrations with stimulation by N.
      meningitidis alone. Our data analysis of the effects of IL-10 on gene expression
      induced by N. meningitidis suggests that high plasma levels of IL-10 in
      meningococcal septic shock plasma may have a profound effect on a variety of
      functions and cellular processes in human monocytes, including cell-to-cell
      signaling, cellular movement, cellular development, antigen presentation, and
      cell death.

PMID- 22966041
TI  - Kinetics of innate immune response to Yersinia pestis after intradermal infection
      in a mouse model.
AB  - A hallmark of Yersinia pestis infection is a delayed inflammatory response early
      in infection. In this study, we use an intradermal model of infection to study
      early innate immune cell recruitment. Mice were injected intradermally in the ear
      with wild-type (WT) or attenuated Y. pestis lacking the pYV virulence plasmid
      (pYV(-)). The inflammatory responses in ear and draining lymph node samples were
      evaluated by flow cytometry and immunohistochemistry. As measured by flow
      cytometry, total neutrophil and macrophage recruitment to the ear in WT-infected
      mice did not differ from phosphate-buffered saline (PBS) controls or mice
      infected with pYV(-), except for a transient increase in macrophages at 6 h
      compared to the PBS control. Limited inflammation was apparent even in animals
      with high bacterial loads (10(5) to 10(6) CFU). In addition, activation of
      inflammatory cells was significantly reduced in WT-infected mice as measured by
      CD11b and major histocompatibility complex class II (MHC-II) expression. When
      mice infected with WT were injected 12 h later at the same intradermal site with
      purified LPS, Y. pestis did not prevent recruitment of neutrophils. However,
      significant reduction in neutrophil activation remained compared to that of PBS
      and pYV(-) controls. Immunohistochemistry revealed qualitative differences in
      neutrophil recruitment to the skin and draining lymph node, with WT-infected mice
      producing a diffuse inflammatory response. In contrast, focal sites of neutrophil
      recruitment were sustained through 48 h postinfection in pYV(-)-infected mice.
      Thus, an important feature of Y. pestis infection is reduced activation and
      organization of inflammatory cells that is at least partially dependent on the
      pYV virulence plasmid.

PMID- 22966038
TI  - Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of
      applications for prevention and treatment of chronic disease.
AB  - We review the rationale for the use of synthetic oleanane triterpenoids (SOs) for
      prevention and treatment of disease, as well as extensive biological data on this
      topic resulting from both cell culture and in vivo studies. Emphasis is placed on
      understanding mechanisms of action. SOs are noncytotoxic drugs with an excellent
      safety profile. Several hundred SOs have now been synthesized and in vitro have
      been shown to: 1) suppress inflammation and oxidative stress and therefore be
      cytoprotective, especially at low nanomolar doses, 2) induce differentiation, and
      3) block cell proliferation and induce apoptosis at higher micromolar doses.
      Animal data on the use of SOs in neurodegenerative diseases and in diseases of
      the eye, lung, cardiovascular system, liver, gastrointestinal tract, and kidney,
      as well as in cancer and in metabolic and inflammatory/autoimmune disorders, are
      reviewed. The importance of the cytoprotective Kelch-like erythroid cell-derived
      protein with CNC homology-associated protein 1/nuclear factor (erythroid-derived
      2)-like 2/antioxidant response element (Keap1/Nrf2/ARE) pathway as a mechanism of
      action is explained, but interactions with peroxisome proliferator-activated
      receptor gamma (PARPgamma), inhibitor of nuclear factor-kappaB kinase complex
      (IKK), janus tyrosine kinase/signal transducer and activator of transcription
      (JAK/STAT), human epidermal growth factor receptor 2 (HER2)/ErbB2/neu,
      phosphatase and tensin homolog (PTEN), the phosphatidylinositol 3-kinase/protein
      kinase B (PI3K/Akt) pathway, mammalian target of rapamycin (mTOR), and the thiol
      proteome are also described. In these interactions, Michael addition of SOs to
      reactive cysteine residues in specific molecular targets triggers biological
      activity. Ultimately, SOs are multifunctional drugs that regulate the activity of
      entire networks. Recent progress in the earliest clinical trials with 2-cyano
      3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) methyl ester (bardoxolone
      methyl) is also summarized.

PMID- 22966042
TI  - The hydroxamate siderophore rhequichelin is required for virulence of the
      pathogenic actinomycete Rhodococcus equi.
AB  - We previously showed that the facultative intracellular pathogen Rhodococcus equi
      produces a nondiffusible and catecholate-containing siderophore (rhequibactin)
      involved in iron acquisition during saprophytic growth. Here, we provide evidence
      that the rhbABCDE cluster directs the biosynthesis of a hydroxamate siderophore,
      rhequichelin, that plays a key role in virulence. The rhbC gene encodes a
      nonribosomal peptide synthetase that is predicted to produce a tetrapeptide
      consisting of N(5)-formyl-N(5)-hydroxyornithine, serine, N(5)-hydroxyornithine,
      and N(5)-acyl-N(5)-hydroxyornithine. The other rhb genes encode putative
      tailoring enzymes mediating modification of ornithine residues incorporated into
      the hydroxamate product of RhbC. Transcription of rhbC was upregulated during
      growth in iron-depleted medium, suggesting that it plays a role in iron
      acquisition. This was confirmed by deletion of rhbCD, rendering the resulting
      strain R. equi SID2 unable to grow in the presence of the iron chelator 2,2
      dipyridyl. Supernatant of the wild-type strain rescued the phenotype of R. equi
      SID2. The importance of rhequichelin in virulence was highlighted by the rapid
      increase in transcription levels of rhbC following infection and the inability of
      R. equi SID2 to grow within macrophages. Unlike the wild-type strain, R. equi
      SID2 was unable to replicate in vivo and was rapidly cleared from the lungs of
      infected mice. Rhequichelin is thus a key virulence-associated factor, although
      nonpathogenic Rhodococcus species also appear to produce rhequichelin or a
      structurally closely related compound. Rhequichelin biosynthesis may therefore be
      considered an example of cooption of a core actinobacterial trait in the
      evolution of R. equi virulence.

PMID- 22966043
TI  - YbcL of uropathogenic Escherichia coli suppresses transepithelial neutrophil
      migration.
AB  - Uropathogenic Escherichia coli (UPEC) strains suppress the acute inflammatory
      response in the urinary tract to ensure access to the intracellular uroepithelial
      niche that supports the propagation of infection. Our understanding of this
      initial cross talk between host and pathogen is incomplete. Here we report the
      identification of a previously uncharacterized periplasmic protein, YbcL, encoded
      by UPEC that contributes to immune modulation in the urinary tract by suppressing
      acute neutrophil migration. In contrast to wild-type UPEC, an isogenic strain
      lacking ybcL expression (UTI89 DeltaybcL) failed to suppress transepithelial
      polymorphonuclear leukocyte (PMN) migration in vitro, a defect complemented by
      expressing ybcL episomally. YbcL homologs are present in many E. coli genomes;
      expression of the YbcL variant encoded by nonpathogenic E. coli K-12 strain
      MG1655 (YbcL(MG)) failed to complement the UTI89 DeltaybcL defect, whereas
      expression of the UPEC YbcL variant (YbcL(UTI)) in MG1655 conferred the capacity
      for suppressing PMN migration. This phenotypic difference was due to a single
      amino acid difference (V78T) between the two YbcL homologs, and a majority of
      clinical UPEC strains examined were found to encode the suppressive YbcL variant.
      Purified YbcL(UTI) protein suppressed PMN migration in response to live or killed
      MG1655, and YbcL(UTI) was detected in the supernatant during UPEC infection of
      bladder epithelial cells or PMNs. Lastly, early PMN influx to murine bladder
      tissue was augmented upon in vivo infection with UTI89 DeltaybcL compared with
      wild-type UPEC. Our findings demonstrate a role for UPEC YbcL in suppression of
      the innate immune response during urinary tract infection.

PMID- 22966044
TI  - Analysis of the mechanisms that underlie absorption of botulinum toxin by the
      inhalation route.
AB  - Botulinum toxin is a highly potent oral and inhalation poison, which means that
      the toxin must have an efficient mechanism for penetration of epithelial
      barriers. To date, three models for toxin passage across epithelial barriers have
      been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an
      auxiliary protein, HA35, transports toxin from the apical to the basal side of
      epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of
      epithelial cells to disrupt tight junctions, and this permits paracellular flux
      of toxin. These models were evaluated by studying toxin absorption following
      inhalation exposure in mice. Three types of experiments were conducted. In the
      first, the potency of pure neurotoxin was compared with that of progenitor toxin
      complex, which contains HA35. The results showed that the rate and extent of
      toxin absorption, as well as the potency of absorbed toxin, did not depend upon,
      nor were they enhanced by, the presence of HA35. In the second type of
      experiment, the potencies of pure neurotoxin and progenitor toxin complex were
      compared in the absence or presence of antibodies on the apical side of
      epithelial cells. Antibodies directed against the neurotoxin protected against
      challenge, but antibodies against HA35 did not. In the final type of experiment,
      the potency of pure neurotoxin and toxin complex was compared in animals
      pretreated to deliver antibodies to the basal side of epithelial cells. Once
      again, antibodies directed against the neurotoxin provided resistance to
      challenge, but antibodies directed against HA35 did not. Taken collectively, the
      data indicate that the toxin by itself is capable of crossing epithelial
      barriers. The data do not support any hypothesis in which HA35 is essential for
      toxin penetration of epithelial barriers.

PMID- 22966045
TI  - Inflammatory monocyte recruitment is regulated by interleukin-23 during systemic
      bacterial infection.
AB  - Listeria monocytogenes is a gram-positive intracellular pathogen that causes
      meningitis and septicemia in immunocompromised individuals and spontaneous
      abortion in pregnant women. The innate immune response against L. monocytogenes
      is primarily mediated by neutrophils and monocytes. Interleukin-23 (IL-23) is an
      important proinflammatory cytokine well known for its role in neutrophil
      recruitment in various infectious and autoimmune diseases. We have previously
      shown that IL-23 is required for host resistance against L. monocytogenes and for
      neutrophil recruitment to the liver, but not the spleen, during infection.
      Despite efficient neutrophil recruitment to the spleen, IL-23p19 knockout (KO)
      mice have an increased bacterial burden in this organ, suggesting that IL-23 may
      regulate the recruitment/function of another cell type to the spleen. In this
      study, we show that specific depletion of neutrophils abrogated the differences
      in bacterial burdens in the livers but not the spleens of C57BL/6 (B6) and IL
      23p19 KO mice. Interestingly, L. monocytogenes-infected IL-23p19 KO mice had
      fewer monocytes in the spleen than B6 mice, as well as a reduction in the
      monocyte-recruiting chemokines CCL2 and CCL7. Additionally, the overall
      concentrations of tumor necrosis factor alpha (TNF-alpha) and nitric oxide
      (NO(*)), as well as the percentages and total numbers of monocytes producing TNF
      alpha and NO(*), were reduced in IL-23p19 KO mice compared to levels in B6 mice,
      leading to increased bacterial burdens in the spleens of L. monocytogenes
      infected IL-23p19 KO mice. Collectively, our data establish that IL-23 is
      required for the optimal recruitment of TNF-alpha- and NO(*)-producing
      inflammatory monocytes, thus revealing a novel mechanism by which this
      proinflammatory cytokine provides protection against bacterial infection.

PMID- 22966046
TI  - Escherichia coli isolates that carry vat, fyuA, chuA, and yfcV efficiently
      colonize the urinary tract.
AB  - Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens,
      encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While
      several virulence factors are associated with ExPEC, there is no core set of
      virulence factors that can be used to definitively differentiate these
      pathotypes. Here we describe a multiplex of four virulence factor-encoding genes,
      yfcV, vat, fyuA, and chuA, highly associated with uropathogenic E. coli strains
      that can distinguish three groups of E. coli: diarrheagenic and animal-associated
      E. coli strains, human commensal and avian pathogenic E. coli strains, and
      uropathogenic and neonatal meningitis E. coli strains. Furthermore, human
      intestinal isolates that encode all four predictor genes express them during
      exponential growth in human urine and colonize the bladder in the mouse model of
      ascending urinary tract infection in higher numbers than human commensal strains
      that do not encode the four predictor genes (P = 0.02), suggesting that the
      presence of the predictors correlates with uropathogenic potential.

PMID- 22966047
TI  - Campylobacter jejuni outer membrane vesicles play an important role in bacterial
      interactions with human intestinal epithelial cells.
AB  - Campylobacter jejuni is the most prevalent cause of food-borne gastroenteritis in
      the developed world; however, the molecular basis of pathogenesis is unclear.
      Secretion of virulence factors is a key mechanism by which enteric bacterial
      pathogens interact with host cells to enhance survival and/or damage the host.
      However, C. jejuni lacks the virulence-associated secretion systems possessed by
      other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles
      (OMVs) for delivery of virulence factors into host cells. In the absence of
      prototypical virulence-associated secretion systems, OMVs could be an important
      alternative for the coordinated delivery of C. jejuni proteins into host cells.
      Proteomic analysis of C. jejuni 11168H OMVs identified 151 proteins, including
      periplasmic and outer membrane-associated proteins, but also many determinants
      known to be important in survival and pathogenesis, including the cytolethal
      distending toxin (CDT). C. jejuni OMVs contained 16 N-linked glycoproteins,
      indicating a delivery mechanism by which these periplasm-located yet immunogenic
      glycoproteins can interact with host cells. C. jejuni OMVs possess cytotoxic
      activity and induce a host immune response from T84 intestinal epithelial cells
      (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin
      B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta
      cyclodextrin partially blocks OMV-induced host immune responses, indicating a
      role for lipid rafts in host cell plasma membranes during interactions with C.
      jejuni OMVs. OMVs isolated from a C. jejuni 11168H cdtA mutant induced
      interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV
      induction of IL-8 is independent of CDT.

PMID- 22966048
TI  - Virulence phenotypes of Legionella pneumophila associated with noncoding RNA
      lpr0035.
AB  - The Philadelphia-1 strain of Legionella pneumophila, the causative organism of
      Legionnaires' disease, contains a recently discovered noncoding RNA, lpr0035.
      lpr0035 straddles the 5' chromosomal junction of a 45-kbp mobile genetic element,
      pLP45, which can exist as an episome or integrated in the bacterial chromosome. A
      121-bp deletion was introduced in strain JR32, a Philadelphia-1 derivative. The
      deletion inactivated lpr0035, removed the 49-bp direct repeat at the 5' junction
      of pLP45, and locked pLP45 in the chromosome. Intracellular multiplication of the
      deletion mutant was decreased by nearly 3 orders of magnitude in Acanthamoeba
      castellanii amoebae and nearly 2 orders of magnitude in J774 mouse macrophages.
      Entry of the deletion mutant into amoebae and macrophages was decreased by >70%.
      The level of entry in both hosts was restored to that in strain JR32 by plasmid
      copies of two open reading frames immediately downstream of the 5' junction and
      plasmid lpr0035 driven by its endogenous promoter. When induced from a tac
      promoter, plasmid lpr0035 completely reversed the intracellular multiplication
      defect in macrophages but was without effect in amoebae. These data are the first
      evidence of a role for noncoding RNA lpr0035, which has homologs in six other
      Legionella genomes, in entry of L. pneumophila into amoebae and macrophages and
      in host-specific intracellular multiplication. The data also demonstrate that
      deletion of a direct-repeat sequence restricts the mobility of pLP45 and is a
      means of studying the role of pLP45 mobility in Legionella virulence phenotypes.

PMID- 22966049
TI  - Enteropathogenic Escherichia coli and vaccinia virus do not require the family of
      WASP-interacting proteins for pathogen-induced actin assembly.
AB  - The human pathogens enteropathogenic Escherichia coli (EPEC) and vaccinia virus
      trigger actin assembly in host cells by activating the host adaptor Nck and the
      actin nucleation promoter neural Wiskott-Aldrich syndrome protein (N-WASP). EPEC
      translocates effector molecules into host cells via type III secretion, and the
      interaction between the translocated intimin receptor (Tir) and the bacterial
      membrane protein intimin stimulates Nck and N-WASP recruitment, leading to the
      formation of actin pedestals beneath adherent bacteria. Vaccinia virus also
      recruits Nck and N-WASP to generate actin tails that promote cell-to-cell spread
      of the virus. In addition to Nck and N-WASP, WASP-interacting protein (WIP)
      localizes to vaccinia virus tails, and inhibition of actin tail formation upon
      ectopic expression of WIP mutants led to the suggestion that WIP is required for
      this process. Similar studies of WIP mutants, however, did not affect the ability
      of EPEC to form actin pedestals, arguing against an essential role for WIP in
      EPEC-induced actin assembly. In this study, we demonstrate that Nck and N-WASP
      are normally recruited by vaccinia virus and EPEC in the absence of WIP, and
      neither WIP nor the WIP family members CR16 and WIRE/WICH are essential for
      pathogen induced actin assembly. In addition, although Nck binds EPEC Tir
      directly, N-WASP is required for its localization during pedestal formation.
      Overall, these data highlight similar pathogenic strategies shared by EPEC and
      vaccinia virus by demonstrating a requirement for both Nck and N-WASP, but not
      WIP or WIP family members in pathogen-induced actin assembly.

PMID- 22966050
TI  - Antigenic characterization of an intrinsically unstructured protein, Plasmodium
      falciparum merozoite surface protein 2.
AB  - Merozoite surface protein 2 (MSP2) is an abundant glycosylphosphatidylinositol
      (GPI)-anchored protein of Plasmodium falciparum, which is a potential component
      of a malaria vaccine. As all forms of MSP2 can be categorized into two allelic
      families, a vaccine containing two representative forms of MSP2 may overcome the
      problem of diversity in this highly polymorphic protein. Monomeric recombinant
      MSP2 is an intrinsically unstructured protein, but its conformational properties
      on the merozoite surface are unknown. This question is addressed here by
      analyzing the 3D7 and FC27 forms of recombinant and parasite MSP2 using a panel
      of monoclonal antibodies raised against recombinant MSP2. The epitopes of all
      antibodies, mapped using both a peptide array and by nuclear magnetic resonance
      (NMR) spectroscopy on full-length recombinant MSP2, were shown to be linear. The
      antibodies revealed antigenic differences, which indicate that the conserved N-
      and C-terminal regions, but not the central variable region, are less accessible
      in the parasite antigen. This appears to be an intrinsic property of parasite
      MSP2 and is not dependent on interactions with other merozoite surface proteins
      as the loss of some conserved-region epitopes seen using the immunofluorescence
      assay (IFA) on parasite smears was also seen on Western blot analyses of parasite
      lysates. Further studies of the structural basis of these antigenic differences
      are required in order to optimize recombinant MSP2 constructs being evaluated as
      potential vaccine components.

PMID- 22966051
TI  - Cysteine-scanning mutagenesis supports the importance of Clostridium perfringens
      enterotoxin amino acids 80 to 106 for membrane insertion and pore formation.
AB  - Clostridium perfringens enterotoxin (CPE) causes the gastrointestinal symptoms of
      the second most common bacterial food-borne illness. Previous studies suggested
      that a region named TM1, which has amphipathic characteristics and spans from
      amino acids 81 to 106 of the native CPE protein, forms a beta-hairpin involved in
      beta-barrel pore formation. To further explore the potential role of TM1 in pore
      formation, the single Cys naturally present in CPE at residue 186 was first
      altered to alanine by mutagenesis; the resultant rCPE variant, named C186A, was
      shown to retain cytotoxic properties. Cys-scanning mutagenesis was then performed
      in which individual Cys mutations were introduced into each TM1 residue of the
      C186A variant. When those Cys variants were characterized, three variants were
      identified that exhibit reduced cytotoxicity despite possessing binding and
      oligomerization abilities similar to those of the C186A variant from which they
      were derived. Pronase challenge experiments suggested that the reduced
      cytotoxicity of those two Cys variants, i.e., the F91C and F95C variants, which
      model to the tip of the beta-hairpin, was attributable to a lessened ability of
      these variants to insert into membranes after oligomerization. In contrast,
      another Cys variant, i.e., the G103C variant, with impaired cytotoxicity
      apparently inserted into membranes after oligomerization but could not form a
      pore with a fully functional channel. Collectively, these results support the TM1
      region forming a beta-hairpin as an important step in CPE insertion and pore
      formation. Furthermore, this work identifies the first amino acid residues
      specifically involved in those two steps in CPE action.

PMID- 22966053
TI  - Ethnic disparities in influenza vaccination in Canada.

PMID- 22966054
TI  - Influenza vaccination coverage across ethnic groups in Canada.
AB  - BACKGROUND: The success of influenza vaccination campaigns may be suboptimal if
      subgroups of the population face unique barriers or have misconceptions about
      vaccination. We conducted a national study to estimate influenza vaccine coverage
      across 12 ethnic groups in Canada to assess the presence of ethnic disparities.
      METHODS: We pooled responses to the Canadian Community Health Survey between 2003
      and 2009 (n = 437 488). We estimated ethnicity-specific self-reported influenza
      vaccine coverage for the overall population, for people aged 65 years and older,
      and for people aged 12-64 years with and without chronic conditions. We used
      weighted logistic regression models to examine the association between ethnicity
      and influenza vaccination, adjusting for sociodemographic factors and health
      status. RESULTS: Influenza vaccination coverage ranged from 25% to 41% across
      ethnic groups. After adjusting for sociodemographic factors and health status for
      people aged 12 years and older, all ethnic groups were more likely to have
      received a vaccination against influenza than people who self-identified as
      white, with the exception of those who self-identified as black (odds ratio [OR]
      1.01, 95% confidence interval [CI] 0.88-1.15). Compared with white Canadians,
      Canadians of Filipino (OR 2.00, 95% CI 1.67-2.40) and Southeast Asian (OR 1.66,
      95% CI 1.36-2.03) descent had the greatest likelihood of having received
      vaccination against influenza. INTERPRETATION: Influenza vaccine coverage in
      Canada varies by ethnicity. Black and white Canadians have the lowest uptake of
      influenza vaccine of the ethnic groups represented in our study. Further research
      is needed to understand the facilitators, barriers and misconceptions relating to
      vaccination that exist across ethnic groups, and to identify promotional
      strategies that may improve uptake among black and white Canadians.

PMID- 22966055
TI  - Effect of a collaborative interdisciplinary maternity care program on perinatal
      outcomes.
AB  - BACKGROUND: The number of physicians providing maternity care in Canada is
      decreasing, and the rate of cesarean delivery is increasing. We evaluated the
      effect on perinatal outcomes of an interdisciplinary program designed to promote
      physiologic birth and encourage active involvement of women and their families in
      maternity care. METHODS: We conducted a retrospective cohort study involving 1238
      women who attended the South Community Birth Program in Vancouver, Canada, from
      April 2004 to October 2010. The program offers comprehensive, collaborative,
      interdisciplinary care from family physicians, midwives, community health nurses
      and doulas to a multiethnic, low-income population. A comparison group, matched
      for neighbourhood of residence, maternal age, parity and gestational age at
      delivery, comprised 1238 women receiving standard care in community-based family
      physician, obstetrician and midwife practices. The primary outcome was the
      proportion of women who underwent cesarean delivery. RESULTS: Compared with women
      receiving standard care, those in the birth program were more likely to be
      delivered by a midwife (41.9% v. 7.4%, p < 0.001) instead of an obstetrician
      (35.5% v. 69.6%, p < 0.001). The program participants were less likely than the
      matched controls to undergo cesarean delivery (relative risk [RR] 0.76, 95%
      confidence interval [CI] 0.68-0.84) and, among those with a previous cesarean
      delivery, more likely to plan a vaginal birth (RR 3.22, 95% CI 2.25-4.62). Length
      of stay in hospital was shorter in the program group for both the mothers (mean
      +/- standard deviation 50.6 +/- 47.1 v. 72.7 +/- 66.7 h, p < 0.001) and the
      newborns (47.5 +/- 92.6 v. 70.6 +/- 126.7 h, p < 0.001). Women in the birth
      program were more likely than the matched controls to be breastfeeding
      exclusively at discharge (RR 2.10, 95% CI 1.85-2.39). INTERPRETATION: Women
      attending a collaborative program of interdisciplinary maternity care were less
      likely to have a cesarean delivery, had shorter hospital stays on average and
      were more likely to breastfeed exclusively than women receiving standard care.

PMID- 22966056
TI  - The science of pesticide-free potato chips.

PMID- 22966057
TI  - National standards urged for end-of-life care providers and facilities.

PMID- 22966060
TI  - Professionalism: the privilege and burden of self-regulation.

PMID- 22966059
TI  - Applying the 2011 Canadian guidelines for breast cancer screening in practice.

PMID- 22966061
TI  - Most of our prescription drugs are manufactured overseas -- but are they safe?

PMID- 22966062
TI  - Recurrent aphthous stomatitis.

PMID- 22966063
TI  - Ptychoderid hemichordate neurulation without a notochord.
AB  - Enteropneust hemichordates share several characteristics with chordates, such as
      a Hox-specified anterior-posterior axis, pharyngeal gill slits, a dorsal central
      nervous system (CNS), and a juvenile postanal tail. Ptychoderid hemichordates,
      such as the indirect-developer Ptychodera flava, have feeding larvae and a
      remarkable capacity to regenerate their CNS. We compared neurulation of
      ptychoderid hemichordates and chordates using histological analyses, and found
      many similarities in CNS development. In ptychoderid hemichordates, which lack a
      notochord, the proboscis skeleton develops from endoderm after neurulation. The
      position of the proboscis skeleton directly under the nerve cord suggests that it
      serves a structural role similar to the notochord of chordates. These results
      suggest that either the CNS preceded evolution of the notochord or that the
      notochord has been lost in hemichordates. The evolution of the notochord remains
      ambiguous, but it may have evolved from endoderm, not mesoderm.

PMID- 22966064
TI  - Environmental proteomics of the mussel Mytilus: implications for tolerance to
      stress and change in limits of biogeographic ranges in response to climate
      change.
AB  - Climate change will affect temperature extremes and averages, and hyposaline
      conditions in coastal areas due to extreme precipitation events and oceanic pH.
      How climate change will push species close to, or beyond, their physiological
      tolerance limits as well as change the limits of their biogeographic ranges can
      probably be investigated best in species that have already responded to climate
      change and whose distribution ranges are currently in flux. Blue mussels provide
      such a study system, with the invading warm-adapted Mediterranean Mytilus
      galloprovincialis having replaced the native more cold-adapted Mytilus trossulus
      from the southern part of its range in southern California over the past century,
      possibly due to climate change. However, freshwater input may prevent the latter
      species from expanding further north. We used a proteomics approach to
      characterize the responses of the two congeners to acute heat stress, chronic
      thermal acclimation, and hyposaline stress. In addition, we investigated the
      proteomic changes in response to decreasing seawater pH in another bivalve, the
      eastern oyster Crassostrea virginica. The results suggest that reactive oxygen
      species (ROS) are a common costressor during environmental stress, including
      oceanic acidification, and possibly cause modifications of cytoskeletal elements.
      All stressors disrupted protein homeostasis, indicated by the induction of
      molecular chaperones and, in the case of acute heat stress, proteasome isoforms,
      possibly due both to protein denaturation directly by the stressor and to the
      production of ROS. Acute stress by heat and hyposalinity changed several small G
      proteins implicated in cytoskeletal modifications and vesicular transport,
      respectively. Changes in abundance of proteins involved in energy metabolism and
      ROS scavenging further suggest a possible trade-off during acute and chronic
      stress from heat and cold between ROS-generating NADH-producing pathways and ROS
      scavenging NADPH-producing pathways, especially through the reaction of NADPH
      dependent isocitrate dehydrogenase and the pentose-phosphate pathway. Some of the
      proteomic changes may not constitute de novo protein synthesis but rather shifts
      in abundance of isoforms differing in posttranslational modifications,
      specifically acetylation by a NAD-dependent deacetylase (sirtuin). Interspecific
      differences suggest that these processes set physiological tolerance limits and
      thereby contribute to recent biogeographic shifts in range, possibly caused by
      climate change.

PMID- 22966065
TI  - The p35 human invariant chain in transgenic mice restores mature B cells in the
      absence of endogenous CD74.
AB  - The invariant chain (Ii; CD74) has pleiotropic functions and Ii-deficient mice
      show defects in MHC class II (MHC II) transport and B cell maturation. In humans,
      but not in mice, a minor Iip35 isoform of unknown function includes an
      endoplasmic reticulum-retention motif that is masked upon binding of MHC II
      molecules. To gain further insight into the roles of Ii in B cell homeostasis, we
      generated Iip35 transgenic mice (Tgp35) and bred these with mice deficient for Ii
      (Tgp35/mIiKO). Iip35 was shown to compete with mIi for the binding to I-A(b)  .
      In addition, classical endosomal degradation products (p20/p10) and the class II
      associated invariant chain peptide (CLIP) fragment were detected. Moreover, Iip35
      favored the formation of compact peptide-MHC II complexes in the Tgp35/mIiKO
      mice. I-A(b) levels were restored at the plasma membrane of mature B cells but
      Iip35 affected the fine conformation of MHC II molecules as judged by the
      increased reactivity of the AF6-120.1 antibody in permeabilized cells. However,
      the human Iip35 cannot fully replace the endogenous Ii. Indeed, most immature B
      cells in the bone marrow and spleen of transgenic mice had reduced surface
      expression of MHC II molecules, demonstrating a dominant-negative effect of Iip35
      in Tgp35 mice. Interestingly, while maturation to follicular B cells was normal,
      Iip35 expression appeared to reduce the proportions of marginal zone B cells.
      These results emphasize the importance of Ii in  B cell homeostasis and suggest
      that Iip35 could have regulatory functions.

PMID- 22966066
TI  - Radiation exposure from CT scans: how to close our knowledge gaps, monitor and
      safeguard exposure--proceedings and recommendations of the Radiation Dose Summit,
      sponsored by NIBIB, February 24-25, 2011.
AB  - This article summarizes the proceedings of a portion of the Radiation Dose
      Summit, which was organized by the National Institute of Biomedical Imaging and
      Bioengineering and held in Bethesda, Maryland, in February 2011. The current
      understandings of ways to optimize the benefit-risk ratio of computed tomography
      (CT) examinations are summarized and recommendations are made for priority areas
      of research to close existing gaps in our knowledge. The prospects of achieving a
      submillisievert effective dose CT examination routinely are assessed.

PMID- 22966067
TI  - Differential cerebellar functional interactions during an interference task
      across multiple sclerosis phenotypes.
AB  - PURPOSE: To determine whether modification of the connections between cerebellar
      and prefrontal areas might vary among multiple sclerosis (MS) phenotypes and
      might be associated with cognitive failure. MATERIALS AND METHODS: Approval of
      the institutional review boards and written informed consent were obtained from
      each participant. Stroop-related functional magnetic resonance (MR) imaging
      activations and effective connectivity abnormalities between the right cerebellum
      and any other brain regions were assessed by using a psychophysiologic
      interaction (PPI) analysis from 17 patients with relapsing-remitting (RR), 17
      with benign, and 23 with secondary progressive (SP) MS and 18 healthy control
      subjects (P < .05, corrected at cluster level). Correlations with disease
      duration, T2 lesion volume, brain volume, and response times (RTs) during the
      incongruent condition were estimated (P < .001, uncorrected). RESULTS: Activation
      and PPI analyses showed that, compared with the other groups, RR MS group had
      abnormal recruitment of regions of the left frontoparietal lobes, whereas
      compared with RR MS group, SP MS group had abnormal recruitment of the cingulum
      or precuneus. Benign MS group had increased activation of the right prefrontal
      cortex, and increased interaction between these regions and the right cerebellum.
      In healthy controls, RTs inversely correlated with activity of right cerebellum
      and several frontoparietal regions. In MS, RTs inversely correlated with
      bilateral cerebellar activity and directly correlated with right precuneus
      activity. In MS, disease duration inversely correlated with right cerebellar
      activity and directly correlated with left inferior frontal gyrus and right
      precuneus activity. Higher T2 lesion volume and lower brain volumes were related
      to activity in these areas. CONCLUSION: Patients with MS who have various
      clinical phenotypes experience different abnormalities in activation and
      effective connectivity between the right cerebellum and frontoparietal areas,
      which contribute to inefficient cortical reorganization, with increasing
      cognitive load. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120216/-/DC1.

PMID- 22966068
TI  - Coronary in-stent restenosis: assessment with CT coronary angiography.
AB  - PURPOSE: To compare accuracy and radiation exposure of a new computed tomographic
      (CT) scanner with improved spatial resolution (scanner A) with those of a CT
      scanner with standard spatial resolution (scanner B) for evaluation of coronary
      in-stent restenosis (ISR) by using invasive coronary angiography (ICA) and
      intravascular ultrasonography (US) as reference methods. MATERIALS AND METHODS:
      Written informed consent was obtained and study protocol was approved by
      institutional ethics committee. A total of 180 consecutive patients (154 men
      [mean age +/- standard deviation, 66 years+/-12; range, 51-79 years] and 36 women
      [mean age, 70 years+/-12; range, 55-83 years]) scheduled to undergo ICA for
      suspected ISR were enrolled. Ninety patients were studied with scanner A (group
      1: 72 men [mean age, 65 years+/-11; range, 52-79], 18 women [mean age, 68 years+/
      12; range, 55-83 years]) and 90 with scanner B (group 2: 74 men [mean age, 64
      years+/-10; range, 51-77 years], 16 women [mean age, 68 years+/-11; range, 55-82
      years). Examination with the two scanners was compared with ICA and intravascular
      US. Radiation dose exposure was estimated. To compare stent evaluability between
      the two groups, chi2 test was used. RESULTS: Stent evaluability was higher in
      group 1 than in group 2 (99% vs 92%, P=.0021). A significantly lower rate of beam
      hardening artifact was observed in group 1 (two cases) than group 2 (12 cases,
      P<.05). For stent-based analysis, sensitivity, specificity, and accuracy of
      multidetector CT for ISR identification were 96%, 95%, and 96% in group 1 and
      90%, 91%, and 91% in group 2, respectively, without statistically significant
      differences. The correlation between percent ISR evaluated at multidetector CT
      versus intravascular US was higher in group 1 than in group 2 (r=0.89 vs r=0.58;
      P=.019). The correlations of diameter and area measurements at reference site and
      stent maximal lumen narrowing site between multidetector CT and intravascular US
      were higher in group 1 than in group 2. Radiation dose was low in both
      multidetector CT groups (1.9 mSv+/-0.2). CONCLUSION: Scanner A, with improved
      spatial resolution, allowed reliable detection and quantification of coronary ISR
      with low radiation exposure.

PMID- 22966069
TI  - Estrogen treatment after ovariectomy protects against fatty liver and may improve
      pathway-selective insulin resistance.
AB  - Pathway-selective insulin resistance where insulin fails to suppress hepatic
      glucose production but promotes liver fat storage may underlie glucose and lipid
      abnormalities after menopause. We tested the mechanisms by which estrogen
      treatment may alter the impact of a high-fat diet (HFD) when given at the time of
      ovariectomy (OVX) in mice. Female C57BL/6J mice underwent sham operation, OVX, or
      OVX with estradiol (E2) treatment and were fed an HFD. Hyperinsulinemic
      euglycemic clamps were used to assess insulin sensitivity, tracer incorporation
      into hepatic lipids, and liver triglyceride export. OVX mice had increased
      adiposity that was prevented with E2 at the time of OVX. E2 treatment increased
      insulin sensitivity with OVX and HFD. In sham and OVX mice, HFD feeding induced
      fatty liver, and insulin reduced hepatic apoB100 and liver triglyceride export.
      E2 treatment reduced liver lipid deposition and prevented the decrease in liver
      triglyceride export during hyperinsulinemia. In mice lacking the liver estrogen
      receptor alpha, E2 after OVX limited adiposity but failed to improve insulin
      sensitivity, to limit liver lipid deposition, and to prevent insulin suppression
      of liver triglyceride export. In conclusion, estrogen treatment may reverse
      aspects of pathway-selective insulin resistance by promoting insulin action on
      glucose metabolism but limiting hepatic lipid deposition.

PMID- 22966070
TI  - Tub has a key role in insulin and leptin signaling and action in vivo in
      hypothalamic nuclei.
AB  - Mutation of tub gene in mice induces obesity, suggesting that tub could be an
      important regulator of energy balance. In the current study, we investigated
      whether insulin, leptin, and obesity can modulate Tub in vivo in hypothalamic
      nuclei, and we investigated possible consequences on energy balance, neuropeptide
      expression, and hepatic glucose metabolism. Food intake, metabolic
      characteristics, signaling proteins, and neuropeptide expression were measured in
      response to fasting and refeeding, intracerebroventricular insulin and leptin,
      and Tub antisense oligonucleotide (ASO). Tub tyrosine phosphorylation (Tub-p-tyr)
      is modulated by nutritional status. Tub is a substrate of insulin receptor
      tyrosine kinase (IRTK) and leptin receptor (LEPR)-Janus kinase 2 (JAK2) in
      hypothalamic nuclei. After leptin or insulin stimulation, Tub translocates to the
      nucleus. Inhibition of Tub expression in hypothalamus by ASO increased food
      intake, fasting blood glucose, and hepatic glucose output, decreased O(2)
      consumption, and blunted the effect of insulin or leptin on proopiomelanocortin,
      thyroid-releasing hormone, melanin-concentrating hormone, and orexin expression.
      In hypothalamus of mice administered a high-fat diet, there is a reduction in
      leptin and insulin-induced Tub-p-tyr and nuclear translocation, which is reversed
      by reducing protein tyrosine phosphatase 1B expression. These results indicate
      that Tub has a key role in the control of insulin and leptin effects on food
      intake, and the modulation of Tub may contribute to insulin and leptin resistance
      in DIO mice.

PMID- 22966071
TI  - Sterol regulatory element-binding protein-1c mediates increase of postprandial
      stearic acid, a potential target for improving insulin resistance, in
      hyperlipidemia.
AB  - Elevated serum free fatty acids (FFAs) levels play an important role in the
      development of insulin resistance (IR) and diabetes. We investigated the dynamic
      changes and the underlying regulatory mechanism of postprandial FFA profile in
      hyperlipidemia (HLP) and their relation with insulin sensitivity in both humans
      and mice. We found that serum stearic acid (SA) is the only fatty acid that is
      increased dramatically in the postprandial state. The elevation of SA is due to
      increased insulin-stimulated de novo synthesis mediated by sterol regulatory
      element-binding protein-1c (SREBP-1c)/acetyl-CoA carboxylase/fatty acid
      synthase/elongation of long-chain fatty acid family member 6 (ELOVL6) and the
      elongation of palmitic acid (PA) catalyzed by ELOVL6. Downregulation of SREBP-1c
      or ELOVL6 by small interfering RNA can reduce SA synthesis in liver and serum SA
      level, followed by amelioration of IR in HLP mice. However, inhibition of SREBP
      1c is more effective in improving IR than suppression of ELOVL6, which resulted
      in accumulation of PA. In summary, increased postprandial SA is caused by the
      insulin-stimulated SREBP-1c pathway and elongation of PA in HLP. Reduction of
      postprandial SA is a good candidate for improving IR, and SREBP-1c is potentially
      a better target to prevent IR and diabetes by decreasing SA.

PMID- 22966072
TI  - Novel and reversible mechanisms of smoking-induced insulin resistance in humans.
AB  - Smoking is the most common cause of preventable morbidity and mortality in the
      United States, in part because it is an independent risk factor for the
      development of insulin resistance and type 2 diabetes. However, mechanisms
      responsible for smoking-induced insulin resistance are unclear. In this study, we
      found smokers were less insulin sensitive compared with controls, which increased
      after either 1 or 2 weeks of smoking cessation. Improvements in insulin
      sensitivity after smoking cessation occurred with normalization of IRS-1(ser636)
      phosphorylation. In muscle cell culture, nicotine exposure significantly
      increased IRS-1(ser636) phosphorylation and decreased insulin sensitivity,
      recapitulating the phenotype of smoking-induced insulin resistance in humans. The
      two pathways known to stimulate IRS-1(ser636) phosphorylation (p44/42 mitogen
      activated protein kinase [MAPK] and mammalian target of rapamycin [mTOR]) were
      both stimulated by nicotine in culture. Inhibition of mTOR, but not p44/42 MAPK,
      during nicotine exposure prevented IRS-1(ser636) phosphorylation and normalized
      insulin sensitivity. These data indicate nicotine induces insulin resistance in
      skeletal muscle by activating mTOR. Therapeutic agents designed to oppose
      skeletal muscle mTOR activation may prevent insulin resistance in humans who are
      unable to stop smoking or are chronically exposed to secondhand smoke.

PMID- 22966073
TI  - The core cysteines, (C909) of islet antigen-2 and (C945) of islet antigen-2beta,
      are crucial to autoantibody binding in type 1 diabetes.
AB  - Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA
      2) autoantibodies (IA-2A), possibly through disulfide bond formation. We
      therefore investigated which cysteines are critical to IA-2A binding in patients
      with newly diagnosed type 1 diabetes. All 10 cysteines in the intracellular
      domain of IA-2 were modified to serine by site-directed mutagenesis, and the
      effects of these changes on autoantibody binding in comparison with wild-type
      control were investigated by radiobinding assay. Mutation of the protein tyrosine
      phosphatase (PTP) core cysteine (C909) in IA-2 caused large reductions in
      autoantibody binding. In contrast, little or no reduction in binding was seen
      following substitution of the other cysteines. Modification of the core cysteine
      (C945) in IA-2beta also greatly reduced autoantibody binding. Lysine substitution
      of glutamate-836 in IA-2 or glutamate-872 in IA-2beta resulted in modest
      reductions in binding and identified a second epitope region. Binding to IA-2 PTP
      and IA-2beta PTP was almost abolished by mutation of both the core cysteine and
      these glutamates. The core cysteine is key to the major PTP conformational
      epitope, but disulfide bonding contributes little to IA-2A epitope integrity. In
      most patients, at disease onset, >90% of antibodies binding to the PTP domain of
      IA-2 recognize just two epitope regions.

PMID- 22966075
TI  - CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease.
AB  - OBJECTIVE: To evaluate the potential role of CC chemokine receptor 5
      (CCR5)Delta32 polymorphism in the susceptibility to and clinical expression of
      Behcet's disease (BD) in a cohort of Italian patients. METHODS: One hundred and
      ninety-six consecutive Italian patients satisfying the ISG criteria for BD were
      followed up for 8 years, and 180 healthy age- and sex-matched blood donors were
      molecularly genotyped for the CCR5Delta32 polymorphism. A standard
      microlymphocytotoxicity technique was used to serotype HLA-B51. The patients were
      subgrouped on the basis of the presence or absence of clinical manifestations.
      RESULTS: The distribution of the CCR5Delta32 genotype differed between BD
      patients and controls (P = 0.02). The CCR5Delta32 allele was more common in BD
      patients than in controls [P = 0.02, odds ratio (OR) 2.28 (95% CI 1.1, 4.8)].
      Carriers of the CCR5Delta32 allele (Delta32/Delta32 + CCR5/Delta32) were
      significantly more common in BD patients than in controls [P = 0.02, OR 2.37 (95%
      CI 1.1, 5.1)]. Population-attributable risk was 7.1%. In categorizing patients
      according to gender, the association between CCR5Delta32 polymorphism and BD was
      similar in females and males (ORs 2.76 and 2.0, respectively). No significant
      differences were found when the frequencies of clinical manifestations were
      compared between CC5RDelta32 allele carriers and non-carriers. CONCLUSION:
      CCR5Delta32 polymorphism is associated with an increased susceptibility to
      develop BD. Chemokines may have a role in the pathophysiology of BD.

PMID- 22966074
TI  - The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene
      expression and glucose homeostasis.
AB  - The type 2 diabetes risk gene TCF7L2 is the effector of the Wnt signaling
      pathway. We found previously that in gut endocrine L-cell lines, TCF7L2 controls
      transcription of the proglucagon gene (gcg), which encodes the incretin hormone
      glucagon-like peptide-1 (GLP-1). Whereas peripheral GLP-1 stimulates insulin
      secretion, brain GLP-1 controls energy homeostasis through yet-to-be defined
      mechanisms. We aim to determine the metabolic effect of a functional knockdown of
      TCF7L2 by generating transgenic mice that express dominant-negative TCF7L2
      (TCF7L2DN) specifically in gcg-expressing cells. The gcg-TCF7L2DN transgenic mice
      showed reduced gcg expression in their gut and brain, but not in pancreas.
      Defects in glucose homeostasis were observed in these mice, associated with
      attenuated plasma insulin levels in response to glucose challenge. The defect in
      glucose disposal was exacerbated with high-fat diet. Brain Wnt activity and
      feeding-mediated hypothalamic AMP-activated protein kinase (AMPK) repression in
      these mice were impaired. Peripheral injection of the cAMP-promoting agent
      forskolin increased brain beta-cat Ser675 phosphorylation and brain gcg
      expression and restored feeding-mediated hypothalamic AMPK repression. We
      conclude that TCF7L2 and Wnt signaling control gut and brain gcg expression and
      glucose homeostasis and speculate that positive cross-talk between Wnt and GLP
      1/cAMP signaling is an underlying mechanism for brain GLP-1 in exerting its
      metabolic functions.

PMID- 22966077
TI  - Effect of feeding glucose, fructose, and inulin on blood glucose and insulin
      concentrations in normal ponies and those predisposed to laminitis.
AB  - Identification of ponies (Equus caballus) at increased risk of pasture-associated
      laminitis would aid in the prevention of the disease. Insulin resistance has been
      associated with laminitis and could be used to identify susceptible individuals.
      Insulin resistance may be diagnosed by feeding supplementary water-soluble
      carbohydrate (WSC) and measuring blood glucose and insulin concentrations. The
      aim of this study was to assess the glycemic and insulinemic responses of 7
      normal (NP) and 5 previously laminitic (PLP), mixed breed, native UK ponies fed
      glucose, fructose, and inulin [1 g/(kg.d) for 3 d] or no supplementary WSC
      (control) in spring and fall after a 7-d adaptation to a pasture or hay diet.
      Blood samples were taken for 12 h after feeding on each day, and baseline and
      peak concentrations and area under the curve (AUC) for glucose and insulin were
      recorded. Linear mixed models were used for statistical analysis. Differences
      between PLP and NP groups were most marked after glucose feeding with differences
      in peak glucose (P = 0.02) and peak insulin (P = 0.016) concentrations. Season
      and diet adaptation also affected results. Peak concentrations of glucose and
      insulin occurred 2 to 4 h after WSC feeding. Peak insulin concentration was
      greater and more variable in fall, particularly in PLP adapted to fall pasture.
      Baseline glucose and insulin concentrations varied between individuals and with
      season and diet adaptation but were not greater in PLP than NP. Insulin AUC was
      greater in PLP than NP after feeding both glucose and fructose (P = 0.017), but
      there were no differences between PLP and NP in glucose AUC. Glycemic and
      insulinemic changes were less (P <= 0.05) after feeding fructose than glucose,
      although differences between PLP and NP were still evident. Minimal changes in
      glucose and insulin concentrations occurred after inulin feeding. Measurement of
      peak insulin 2 h after feeding of a single dose of glucose (1 g/kg) may be a
      simple and practical way to aid identification of laminitis-prone ponies before
      the onset of clinical disease, particularly when ponies are adapted to eating
      fall pasture.

PMID- 22966078
TI  - Effects of two different dietary sources of long chain omega-3, highly
      unsaturated fatty acids on incorporation into the plasma, red blood cell, and
      skeletal muscle in horses.
AB  - The objective of this study was to examine the effects of different sources of
      dietary omega-3 (n-3) fatty acid supplementation on plasma, red blood cell, and
      skeletal muscle fatty acid compositions in horses. Twenty-one mares were blocked
      by age, BW, and BCS and assigned to 1 of 3 dietary treatments with 7 mares per
      treatment. Dietary treatments were: 1) control or no fatty acid supplement (CON),
      2) 38 g of n-3 long chain, highly unsaturated fatty acid (LCHUFA) supplement/d
      provided by algae and fish oil (MARINE) containing alpha-linolenic acid (ALA),
      eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic
      acid (DPA), and 3) 38 g of n-3 LCHUFA supplement/d provided by a flaxseed meal
      (FLAX) containing ALA. Each supplement was added to a basal diet consisting of
      hay and barley and was fed for 90 d. Blood samples and muscle middle gluteal
      biopsies were taken at d 0, 30, 60 and 90 of supplementation. Plasma, red blood
      cell and skeletal muscle fatty acid profiles were determined via gas
      chromatography. Plasma linoleic acid (LA) and ALA were at least 10 and 60% less
      (P < 0.01), respectively, in the MARINE compared with the FLAX and CON groups.
      Plasma EPA and DHA were only detected in the MARINE group, and EPA increased 40%
      (P < 0.001) from d 30 to 60, and DHA 19% (P < 0.01) from d 30 to 90. Red blood
      cell LA and ALA were not different among treatments. Red blood cell EPA and DHA
      were only detected in the MARINE group, where EPA increased 38% (P < 0.01) from d
      30 to 60, and DHA increased 56% (P < 0.001) between d 30 and 90. Skeletal muscle
      LA was at least 17% less (P < 0.001) in the MARINE group compared with the other
      treatments. Skeletal muscle ALA was 15% less (P = 0.03) in the MARINE group
      compared with FLAX and CON groups. Skeletal muscle EPA was at least 25% greater
      (P < 0.001) in MARINE group compared with other treatments and increased (P <
      0.001) by 71% from d 30 to 60. Skeletal muscle DHA was at least 57% greater (P <
      0.001) in the MARINE group compared with other groups and increased (P < 0.001)
      by 40% between d 30 and 90. As far as the authors are aware, this is the first
      study to demonstrate that dietary fatty acid supplementation will affect muscle
      fatty acid composition in horses. Incorporation of n-3 LCHUFA into blood and
      muscle depends directly on dietary supply of specific fatty acids.

PMID- 22966079
TI  - Organ weight, intestinal morphology, and fasting whole-body oxygen consumption in
      growing pigs fed diets containing distillers dried grains with solubles alone or
      in combination with a multienzyme supplement.
AB  - The effects of adding a multienzyme complex to a diet containing distillers dried
      grains with solubles (DDGS) produced from a 1:1 mixture of corn and wheat on
      visceral organ weight, intestinal morphology, and fasting whole-body oxygen
      consumption (FWBOC) were investigated in growing pigs in a 28-d trial. Twenty
      four pigs (BW = 19.9 +/- 0.5 kg) were individually housed in floor pens and
      randomly assigned to 3 experimental diets (8 pigs per diet). The diets contained
      corn and soybean meal with 0% (control) or 30% DDGS (DDGS diet); the third diet
      was supplemented with a multienzyme complex in addition to the 30% DDGS (DDGS +
      enzyme diet). All diets had similar nutrient concentrations and met the 1998 NRC
      nutrient requirements for growing pigs. Pigs were fed at 4% of their BW once
      daily. On d 15, 4 pigs from each dietary treatment were randomly selected for
      measurement of FWBOC during the 24- to 30-h postprandial period using an open
      circuit indirect calorimeter. At the end of the study, pigs were killed to
      determine visceral organ weights, ileal and cecal digesta viscosity, and
      intestinal morphology. There was no effect (P > 0.05) of dietary treatment on
      final BW, WBFOC, or digesta viscosity. Empty BW of pigs fed the control diet was
      heavier (P = 0.02) than that of pigs fed the DDGS diet, but the empty BW of pigs
      fed the DDGS + enzyme diet was not different (P > 0.05) from that of pigs fed the
      control or DDGS diet. There were no differences (P > 0.05) in empty BW of liver,
      spleen, pancreas, heart, stomach, small intestine, and cecum among dietary
      treatments on a per kilogram basis. However, pigs fed the DDGS diet had heavier
      (P < 0.05) colon plus rectum and portal-drained viscera (PDV) than pigs fed the
      control diet, but weights of colon plus rectum and PDV in pigs fed the DDGS +
      enzyme diet were not different (P > 0.05) from those of pigs fed the control
      diet. Although morphological data showed no differences (P > 0.05) in the
      duodenum, jejunum, and colon segments among dietary treatments, the DDGS diet
      tended to decrease (P < 0.10) villous height and villous height to crypt depth in
      the ileum. The results of this experiment indicated that pigs fed a diet
      containing 30% DDGS have reduced dressing percentage and increased visceral organ
      mass compared with pigs fed a corn-soybean meal diet. However, the addition of a
      multienzyme complex to the DDGS diet resulted in pigs having a dressing
      percentage and visceral organ mass that are not different from those of pigs fed
      a corn-soybean meal diet.

PMID- 22966080
TI  - Behavioral changes in neonatal swine after an 8-hour rest during prolonged
      transportation.
AB  - Long distance transportation of weaned piglets (Sus scrofa) is increasingly
      common in the united states and may result in delayed eating, drinking, or normal
      social behaviors. A potential solution is a mid-journey rest (lairage). The
      objective of this study was to determine if a lairage altered behavior after a 16
      h transport. Pigs that weighed approximately 18 kg each (n = 894) were housed in
      16 pens with 8 pens per treatment. Lairaged pigs were transported for 8 h and
      given an 8-h rest with food and water, whereas control pigs were transported
      continuously for 16 h. The heaviest, the lightest, and 2 average-BW pigs relative
      to the average weight of the pen were observed by video recording for 24 h
      immediately before and after transport, and during d 6 and 13 after transport.
      Postures (lying, sitting, and standing) were recorded using 10-min-interval scan
      sampling, and behavioral categories included inactivity, activities (eating,
      drinking, alert, manipulating pen, rooting, and walking) and social interactions
      (aggression, belly nosing, playing, tail biting, and positive social behaviors).
      In both treatments, sitting occurred most before transport (P < 0.01) than at
      other times, but did not differ between treatments. Standing increased (time
      effect; P < 0.01) for both treatments immediately after transport through d 6,
      but returned to pre-transport values by d 13. In contrast, lying decreased (time
      effect; P < 0.01) after transport, but returned to above pre-transport values by
      d 13. Time effects were evident for activity (P < 0.01), pen manipulation (P =
      0.05), rooting (P < 0.01), initiation of belly-nosing (P = 0.01), and receiving
      belly-nosing (P = 0.03); however, initiation of aggression did not differ for day
      (P = 0.19) or treatment (P = 0.56). Lairaged pigs initiated more (P = 0.05) play
      than continuously transported pigs, but no differences (P = 0.84) were seen in
      receipt of play behavior. Pigs that were to be transported for 16 h continuously
      walked less pre-transport, walked more post-transport (treatment * time
      interaction; P = 0.02), and drank less pre-transport, but drank more on all days
      post-transport compared with the lairage group (treatment * time interaction; P =
      0.001). This study indicated that extended transport without lairage alters some
      swine behaviors relevant to production (water consumption) and demonstrated that
      a long-duration transport, regardless of the mid-journey lairage treatment,
      affects a number of behaviors up to 13 d after transportation.

PMID- 22966081
TI  - Effects of trailer design on animal welfare parameters and carcass and meat
      quality of three Pietrain crosses being transported over a long distance.
AB  - This study aimed at evaluating the effects of trailer design on stress responses
      and meat quality traits of 3 different pig crosses: 50% Pietrain breeding with
      halothane (HAL)(Nn) (50Nn); 50% Pietrain breeding with HAL(NN) (50NN); and 25%
      Pietrain breeding with HAL(NN) genotype (25NN). Over a 6-wk period, pigs (120
      pigs/crossbreed) were transported for 7 h in either a pot-belly (PB) or flat-deck
      (FD) trailer (10 pigs/crossbreed(-1).trailer(-1).wk(-1)). Temperature (T) and
      relative humidity (RH) were monitored in each trailer. Behaviors during loading
      and unloading, time to load and unload, and latency to rest in lairage were
      recorded, whereas a sub-population of pigs (4 pigs/crossbreed(-1).trailer(-1).wk(
      1)) was equipped with gastro-intestinal tract (GIT) temperature monitors. Blood
      samples were collected at exsanguination for measurement of cortisol, creatine
      kinase (CK), lactate, haptoglobin, and Pig-MAP concentrations. Meat quality data
      were collected at 24 h postmortem from the LM and semimembranosus (SM) and
      adductor (AD) muscles of all 360 pigs. Greater T were recorded in the PB trailer
      during transportation (P = 0.006) and unloading (P < 0.001). Delta GIT
      temperature was greater (P = 0.01) in pigs unloaded from the PB. At loading, pigs
      tended to move backwards more (P = 0.06) when loaded on the FD than the PB
      trailer. At unloading, an interaction was found between trailer type and
      crossbreed type, with a greater (P < 0.01) frequency of overlaps in 50NN and 25NN
      pigs and slips/falls in 50Nn and 50NN pigs from the FD than the PB trailer.
      Cortisol concentrations at slaughter were greater (P = 0.02) in pigs transported
      in the PB than FD trailer. Greater lactate concentrations were found in 50Nn and
      50NN pigs (P = 0.003) and greater CK concentrations (P < 0.001) in 50Nn pigs. As
      expected, 50Nn pigs produced leaner (P < 0.001) carcasses, with greater (P =
      0.01) dressing percentages, as well as lower (P < 0.001) ultimate pH values and
      greater (P < 0.001) drip loss percentages in the LM and greater (P = 0.002) drip
      losses and a paler color (greater L* values, P = 0.02) in the SM than 50NN pigs.
      When used for long distance transportation under controlled conditions, the PB
      trailer produced no detrimental effects on animal welfare or pork quality. Pigs
      with 50% Pietrain crossbreeding appear to be more responsive to transport stress,
      having the potential to produce acceptable carcass and pork quality, provided
      pigs are free of the HAL gene.

PMID- 22966082
TI  - Quantification of saleable meat yield using objective measurements captured by
      video image analysis technology.
AB  - Video image analysis (VIA) images from grain-finished beef carcasses [n = 211; of
      which 63 did not receive zilpaterol hydrochloride (ZIL) and 148 received ZIL
      before harvest] were analyzed for indicators of muscle and fat to illustrate the
      ability to improve methodology to predict saleable meat yield of cattle fed and
      not fed ZIL. Carcasses were processed in large commercial beef processing
      facilities and were fabricated into standard subprimals, fat, and bone. Images
      taken by VIA technology were evaluated using computer image analysis software to
      quantify fat and lean parameters which were subsequently used in multiple-linear
      regression models to predict percentage of saleable meat yield for each carcass.
      Prediction models included variables currently quantified by VIA technology such
      as LM area (LMA), subcutaneous (SC) fat thickness at 75% the length of the LM
      (SFT75), and intramuscular fat score (IMF). Additional distance and area measures
      included LM width (LW), LM depth (LD), iliocostalis muscle area (IA), SC fat
      thickness at 25, 50, and 100% the length of the LM (SFT25, SFT50, SFT100), SC fat
      area from 25 to 100% the length of the LM (SCFA), and SC fat area adjacent to the
      75% length of the LM from the spinous processes (SCFA75). Multiple ratio and
      product variables were also created from distance and area measures. For
      carcasses in this investigation, a 6 variable equation (Adj. R(2) = 0.62, MSE =
      0.022) was calculated which included coefficients for ZIL treatment, SCFA75, LW,
      SCFA, SCFA/HCW, and SFT100/HCW. Use of parameters in the U.S. (Adj. R(2) = 0.39,
      MSE = 0.028) and Canadian [Adj. R(2) = 0.10, root mean square error (MSE) =
      0.034] yield grade equations lack the predictability of the newly adapted
      equations developed for ZIL-fed and non-ZIL-fed cattle. Prediction equations
      developed in this study indicate that the use of VIA technology to quantify
      measurements taken at the 12th/13th rib separation could be used to predict
      saleable meat yield more accurately than those currently in use by U.S. and
      Canadian grading systems. Improvement in saleable meat yield prediction has the
      potential to decrease boxed beef variability via more homogeneous classification
      of carcass fabrication yield.

PMID- 22966083
TI  - CD31 exhibits multiple roles in regulating T lymphocyte trafficking in vivo.
AB  - The role of CD31, an Ig-like molecule expressed by leukocytes and endothelial
      cells (ECs), in the regulation of T lymphocyte trafficking remains contentious.
      Using CD31-deficient mice, we show that CD31 regulates both constitutive and
      inflammation-induced T cell migration in vivo. Specifically, T cell:EC
      interactions mediated by CD31 molecules are required for efficient localization
      of naive T lymphocytes to secondary lymphoid tissue and constitutive
      recirculation of primed T cells to nonlymphoid tissues. In inflammatory
      conditions, T cell:EC CD31-mediated interactions facilitate T cell recruitment to
      Ag-rich sites. However, endothelial CD31 also provides a gate-keeping mechanism
      to limit the rate of Ag-driven T cell extravasation. This event contributes to
      the formation of Ag-specific effector T cell infiltrates and is induced by
      recognition of Ag on the endothelium. In this context, CD31 engagement is
      required for restoring endothelial continuity, which is temporarily lost upon MHC
      molecule ligation by migrating cognate T cells. We propose that integrated
      adhesive and signaling functions of CD31 molecules exert a complex regulation of
      T cell trafficking, a process that is differentially adapted depending on cell
      specific expression, the presence of inflammatory conditions and the molecular
      mechanism facilitating T cell extravasation.

PMID- 22966084
TI  - HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia
      virus by favoring the presentation of peptides with longer HLA-DM-mediated half
      lives.
AB  - HLA-DM (DM) is a nonclassical MHC class II (MHC II) protein that acts as a
      peptide editor to mediate the exchange of peptides loaded onto MHC II during Ag
      presentation. Although the ability of DM to promote peptide exchange in vitro and
      in vivo is well established, the role of DM in epitope selection is still
      unclear, especially in human response to infectious disease. In this study, we
      addressed this question in the context of the human CD4 T cell response to
      vaccinia virus. We measured the IC(50), intrinsic dissociation t(1/2), and DM
      mediated dissociation t(1/2) for a large set of peptides derived from the major
      core protein A10L and other known vaccinia epitopes bound to HLA-DR1 and compared
      these properties to the presence and magnitude of peptide-specific CD4(+) T cell
      responses. We found that MHC II-peptide complex kinetic stability in the presence
      of DM distinguishes T cell epitopes from nonrecognized peptides in A10L peptides
      and also in a set of predicted tight binders from the entire vaccinia genome.
      Taken together, these analyses demonstrate that DM-mediated dissociation t(1/2)
      is a strong and independent factor governing peptide immunogenicity by favoring
      the presentation of peptides with greater kinetic stability in the presence of
      DM.

PMID- 22966085
TI  - Mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin
      pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required
      for alternative pathway function.
AB  - The lectin pathway of complement is an important component of innate immunity.
      Its activation has been thought to occur via recognition of pathogens by mannan
      binding lectin (MBL) or ficolins in complex with MBL-associated serine protease
      (MASP)-2, followed by MASP-2 autoactivation and cleavage of C4 and C2 generating
      the C3 convertase. MASP-1 and MASP-3 are related proteases found in similar
      complexes. MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary
      C2 cleavage. In mice, MASP-1 and MASP-3 have been reported to be central also to
      alternative pathway function through activation of profactor D and factor B. In
      this study, we present functional studies based on a patient harboring a nonsense
      mutation in the common part of the MASP1 gene and hence deficient in both MASP-1
      and MASP-3. Surprisingly, we find that the alternative pathway in this patient
      functions normally, and is unaffected by reconstitution with MASP-1 and MASP-3.
      Conversely, we find that the patient has a nonfunctional lectin pathway, which
      can be restored by MASP-1, implying that this component is crucial for complement
      activation. We show that, although MASP-2 is able to autoactivate under
      artificial conditions, MASP-1 dramatically increases lectin pathway activity at
      physiological conditions through direct activation of MASP-2. We further
      demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex, and
      that such cocomplexes are found in serum, providing a scenario for
      transactivation of MASP-2. Hence, in functional terms, it appears that MASP-1 and
      MASP-2 act in a manner analogous to that of C1r and C1s of the classical pathway.

PMID- 22966087
TI  - The essential polysome-associated RNA-binding protein RBP42 targets mRNAs
      involved in Trypanosoma brucei energy metabolism.
AB  - RNA-binding proteins that target mRNA coding regions are emerging as regulators
      of post-transcriptional processes in eukaryotes. Here we describe a newly
      identified RNA-binding protein, RBP42, which targets the coding region of mRNAs
      in the insect form of the African trypanosome, Trypanosoma brucei. RBP42 is an
      essential protein and associates with polysome-bound mRNAs in the cytoplasm. A
      global survey of RBP42-bound mRNAs was performed by applying HITS-CLIP
      technology, which captures protein-RNA interactions in vivo using UV light.
      Specific RBP42-mRNA interactions, as well as mRNA interactions with a known RNA
      binding protein, were purified using specific antibodies. Target RNA sequences
      were identified and quantified using high-throughput RNA sequencing. Analysis
      revealed that RBP42 bound mainly within the coding region of mRNAs that encode
      proteins involved in cellular energy metabolism. Although the mechanism of
      RBP42's function is unclear at present, we speculate that RBP42 plays a critical
      role in modulating T. brucei energy metabolism.

PMID- 22966088
TI  - Angiopoietin-like protein 2 and risk of type 2 diabetes in a general Japanese
      population: the Hisayama study.
AB  - OBJECTIVE: To examine, for the first time, the association between a novel
      inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development
      of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS: A total of 2,164
      community-dwelling Japanese individuals aged 40 to 79 years without diabetes were
      followed up for 7 years. Serum ANGPTL2 levels were divided into quartile
      categories at baseline: <2.15, 2.16-2.71, 2.72-3.40, and >=3.41 ng/mL. During
      follow-up, 221 participants developed T2DM. RESULTS: In multivariate analyses,
      after adjusting for comprehensive risk factors and high-sensitivity C-reactive
      protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in
      the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95%
      CI, 1.14-2.85; P = 0.01). CONCLUSIONS: Elevated serum ANGPTL2 levels were
      positively associated with the development of T2DM in a general population,
      independent of other risk factors including hs-CRP levels.

PMID- 22966086
TI  - Increased memory differentiation is associated with decreased polyfunctionality
      for HIV but not for cytomegalovirus-specific CD8+ T cells.
AB  - The generation of polyfunctional CD8(+) T cells, in response to vaccination or
      natural infection, has been associated with improved protective immunity.
      However, it is unclear whether the maintenance of polyfunctionality is related to
      particular cellular phenotypic characteristics. To determine whether the cytokine
      expression profile is linked to the memory differentiation stage, we analyzed the
      degree of polyfunctionality of HIV-specific CD8(+) T cells within different
      memory subpopulations in 20 antiretroviral therapy-naive HIV-1-infected
      individuals at ~34 wk postinfection. These profiles were compared with CMV
      specific CD8(+) T cell responses in HIV-uninfected control subjects and in
      individuals chronically infected with HIV. Our results showed that the
      polyfunctional abilities of HIV-specific CD8(+) T cells differed according to
      their memory phenotype. Early-differentiated cells (CD45RO(+)CD27(+)) exhibited a
      higher proportion of cells positive for three or four functions (p < 0.001), and
      a lower proportion of monofunctional cells (p < 0.001) compared with terminally
      differentiated (TD; CD45RO(-)CD27(-)) HIV-specific CD8(+) T cells. The majority
      of TD HIV-specific CD8(+) T cells were monofunctional (median 69% [interquartile
      range: 57-83]), producing predominantly CD107a or MIP1beta. Moreover, proportions
      of HIV-specific monofunctional CD8(+) T cells positively associated with
      proportions of TD HIV-specific CD8(+) T cells (p = 0.019, r = 0.54). In contrast,
      CMV-specific CD8(+) T cell polyfunctional capacities were similar across all
      memory subpopulations, with terminally and early-differentiated cells endowed
      with comparable polyfunctionality. Overall, these data show that the
      polyfunctional abilities of HIV-specific CD8(+) T cells are influenced by the
      stage of memory differentiation, which is not the case for CMV-specific
      responses.

PMID- 22966089
TI  - Insulin resistance and truncal obesity as important determinants of the greater
      incidence of diabetes in Indian Asians and African Caribbeans compared with
      Europeans: the Southall And Brent REvisited (SABRE) cohort.
AB  - OBJECTIVE: To determine the extent of, and reasons for, ethnic differences in
      type 2 diabetes incidence in the U.K. RESEARCH DESIGN AND METHODS: Population
      based triethnic cohort. Participants were without diabetes, aged 40-69 at
      baseline (1989-1991), and followed-up for 20 years. Baseline measurements
      included fasting and postglucose bloods, anthropometry, and lifestyle
      questionnaire. Incident diabetes was identified from medical records and
      participant recall. Ethnic differences in diabetes incidence were examined using
      competing risks regression. RESULTS: Incident diabetes was identified in 196 of
      1,354 (14%) Europeans, 282 of 839 (34%) Indian Asians, and 100 of 335 (30%)
      African Caribbeans. All Indian Asians and African Caribbeans were first
      generation migrants. Compared with Europeans, age-adjusted subhazard ratios (SHRs
      [95% CI]) for men and women, respectively, were 2.88 (95%, 2.36-3.53; P < 0.001)
      and 1.91 (1.18-3.10; P = 0.008) in Indian Asians, and 2.23 (1.64-3.03; P < 0.001)
      and 2.51 (1.63-3.87; P < 0.001) in African Caribbeans. Differences in baseline
      insulin resistance and truncal obesity largely attenuated the ethnic minority
      excess in women (adjusted SHRs: Indian Asians 0.77 [0.49-1.42]; P = 0.3; African
      Caribbeans 1.48 [0.89-2.45]; P = 0.13), but not in men (adjusted SHRs: Indian
      Asians 1.98 [1.52-2.58]; P < 0.001 and African Caribbeans, 2.05 [1.46-2.89; P <
      0.001]). CONCLUSIONS: Insulin resistance and truncal obesity account for the
      twofold excess incidence of diabetes in Indian Asian and African Caribbean women,
      but not men. Explanations for the excess diabetes risk in ethnic minority men
      remains unclear. Further study requires more precise measures of conventional
      risk factors and identification of novel risk factors.

PMID- 22966090
TI  - White matter structural differences in young children with type 1 diabetes: a
      diffusion tensor imaging study.
AB  - OBJECTIVE: To detect clinical correlates of cognitive abilities and white matter
      (WM) microstructural changes using diffusion tensor imaging (DTI) in young
      children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Children, ages 3 to
      <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control
      subjects (n = 14) completed neurocognitive testing and DTI scans. RESULTS:
      Compared with healthy controls, children with type 1 diabetes had lower axial
      diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions.
      There were no significant differences between groups in fractional anisotropy and
      radial diffusivity (RD). Within the diabetes group, there was a significant,
      positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher,
      time-weighted HbA(1c) value was significantly correlated with lower overall
      intellectual functioning measured by the full-scale intelligence quotient (P =
      0.03). CONCLUSIONS: Children with type 1 diabetes had significantly different WM
      structure (as measured by AD) when compared with controls. In addition, WM
      structural differences (as measured by RD) were significantly correlated with
      their HbA(1c) values. Additional studies are needed to determine if WM
      microstructural differences in young children with type 1 diabetes predict future
      neurocognitive outcome.

PMID- 22966091
TI  - Does insulin glargine increase the risk of cancer compared with other basal
      insulins?: A French nationwide cohort study based on national administrative
      databases.
AB  - OBJECTIVE: To explore in France the relationship between insulin glargine use and
      overall and specific cancer risks in type 2 diabetic patients compared with other
      basal insulins. RESEARCH DESIGN AND METHODS: Data were extracted from French
      health insurance information system (Systeme National d'Information Inter-Regimes
      de l'Assurance Maladie) linked with data from the French Hospital Discharge
      database (Programme de Medicalisation des Systemes d'Information). Included were
      70,027 patients aged 40-79 years who started a basal insulin in 2007-2009. Cox
      proportional hazards models with age as time-scale were used to calculate
      multivariate-adjusted hazard ratios for associations between type of basal
      insulin and risk of overall cancer, breast cancer, and seven other cancer sites.
      RESULTS: The median follow-up was 2.67 years in patients exposed to insulin
      glargine. Absolute event rates for all cancer in patients exposed to glargine
      versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years,
      respectively. No significant association was observed between glargine exposure
      and overall cancer incidence after adjustment for sex, with a hazard ratio of
      0.97 (95% CI 0.87-1.07), or after additional adjustment for any other
      hypoglycemic agent use and duration of diabetes. No increased risk of breast
      cancer was observed for glargine users compared with other basal insulins users,
      with a fully adjusted hazard ratio of 1.08 (0.72-1.62). CONCLUSIONS: In a large
      cohort of patients newly treated by basal insulin, no increased risk of any
      cancer was observed in insulin glargine users compared with other basal insulin
      users. Because follow-up did not exceed 4 years, longer-term studies are needed.

PMID- 22966092
TI  - Comparative effectiveness of lifestyle intervention efforts in the community:
      results of the Rethinking Eating and ACTivity (REACT) study.
AB  - OBJECTIVE: To determine the comparative effectiveness of three lifestyle
      intervention modalities in decreasing risk for diabetes. RESEARCH DESIGN AND
      METHODS: Five hundred and fifty-five individuals (86.1% female, 95.1% white, and
      55.8% obese) from eight rural communities were screened for BMI >=25 kg/m(2) and
      waist circumference >40 inches in men and >35 inches in women. Communities with
      their eligible participants (n = 493; mean age 51 years, 87.6% female, 94.1%
      Caucasian) were assigned to four Group Lifestyle Balance (GLB) intervention
      groups: face to face (FF) (n = 119), DVD (n = 113), internet (INT) (n = 101), and
      self-selection (SS) (n = 101). SS participants chose the GLB modality. GLB is a
      comprehensive lifestyle behavior-change program. RESULTS: A marked decline was
      observed in weight after the intervention in all groups (FF -12.5 lbs, P = 0.01;
      DVD -12.2 lbs, P < 0.0001; INT -13.7 lbs, P < 0.0001; and SS -14 lbs, P <
      0.0001). Participants in SS experienced the largest average weight loss. Weight
      loss was sustained in >90% of participants in each group at 6 months (FF 90.7%,
      DVD 90.9%, INT 92.1%, and SS 100%). All groups experienced improvements in the
      proportion of participants with CVD risk factors. The proportion of individuals
      with CVD risk factors remained steady between 3 and 6 months in all groups and
      never returned back to baseline. All associations remained after multivariate
      adjustment. CONCLUSIONS: Despite the modality, the GLB intervention was effective
      at decreasing weight and improving CVD risk factor control. SS and FF
      participants experienced greater improvements in outcomes compared with other
      groups, establishing the importance of patient-centered decision making and a
      support network for successful behavior change.

PMID- 22966093
TI  - Change in visceral adiposity independently predicts a greater risk of developing
      type 2 diabetes over 10 years in Japanese Americans.
AB  - OBJECTIVE: Visceral adiposity is an important risk factor for cardiovascular
      disease and type 2 diabetes. We sought to determine whether change in
      intraabdominal fat area (IAF) over time predicts subsequent development of
      diabetes. RESEARCH DESIGN AND METHODS: We followed up 436 nondiabetic Japanese
      American subjects (mean age 51.9 years, mean BMI 24.2 kg/m(2), 54% male) for
      development of diabetes. We fit a logistic regression model to examine the
      association over a 10-year follow-up between change in IAF at 5-year follow-up
      and other fat areas (measured by computed tomography) and development of incident
      diabetes, adjusted for age, sex, family history of diabetes in a first-degree
      relative, second-generation versus third-generation Japanese American (Nisei vs.
      Sansei), baseline IAF, BMI, weight change over time, smoking status, physical
      activity level, and subcutaneous fat (SCF) depot areas. RESULTS: Cumulative
      incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm(2).
      An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds
      of diabetes over 10 years (OR = 1.65, 95% CI 1.21-2.25) after adjusting for the
      above covariates. This association was also independent of changes in thoracic,
      thigh, and abdominal SCF, as well as change in weight. CONCLUSIONS: We conclude
      that baseline IAF and accumulation of fat in this area over time are independent
      predictors of the development of type 2 diabetes in Japanese Americans.

PMID- 22966094
TI  - Benefits of early hypertension control on cardiovascular outcomes in patients
      with diabetes.
AB  - OBJECTIVE: To assess the impact of early hypertension (HT) control on occurrence
      of subsequent major cardiovascular events in those with diabetes and recent-onset
      HT. RESEARCH DESIGN AND METHODS: Study subjects were 15,665 adults with diabetes
      but no diagnosed coronary or cerebrovascular disease at baseline who met standard
      criteria for new-onset HT. Poisson regression models assessed whether adequate
      blood pressure control within 1 year of HT onset predicts subsequent occurrence
      of major cardiovascular events with and without adjustment for baseline
      Framingham Risk Score (FRS) and other covariates. RESULTS: Mean age was 51.5
      years, and mean blood pressure at HT onset was 136.8/80.8 mmHg. In the year after
      HT onset, mean blood pressure decreased to 131.4/78.0 mmHg and was <130/80 mmHg
      in 32.9% of subjects and <140/90 mmHg in 80.2%. Over a mean follow-up of 3.2
      years, age-adjusted rates of major cardiovascular events in those with mean 1
      year blood pressure measurements of <130/80, 130-139/80-89, and >=140/90 mmHg
      were 5.10, 4.27, and 6.94 events/1,000 person-years, respectively (P = 0.004). In
      FRS-adjusted models, rates of major cardiovascular events were significantly
      higher in those with mean blood pressure >=140/90 mmHg in the first year after HT
      onset (rate ratio 1.30 [95% CI 1.01-1.169]; P = 0.04). CONCLUSIONS: Failure to
      adequately control BP within 1 year of HT onset significantly increased the
      likelihood of major cardiovascular events within 3 years. Prompt control of new
      onset HT in patients with diabetes may provide important short-term clinical
      benefits.

PMID- 22966095
TI  - Maternal physical activity and insulin action in pregnancy and their
      relationships with infant body composition.
AB  - OBJECTIVE: We sought to assess the association between maternal gestational
      physical activity and insulin action and body composition in early infancy.
      RESEARCH DESIGN AND METHODS: At 28-32 weeks' gestation, pregnant women
      participating in an observational study in Sweden underwent assessments of
      height, weight, and body composition, an oral glucose tolerance test, and 10 days
      of objective physical activity assessment. Thirty mothers and infants returned at
      11-19 weeks postpartum. Infants underwent assessments of weight, length, and body
      composition. RESULTS: Early insulin response was correlated with total physical
      activity (r = -0.47; P = 0.007). Early insulin response (r = -0.36; P = 0.045)
      and total physical activity (r = 0.52; P = 0.037) were also correlated with
      infant fat-free mass. No maternal variable was significantly correlated with
      infant adiposity. CONCLUSIONS: The relationships between maternal physical
      activity, insulin response, and infant fat-free mass suggest that physical
      activity during pregnancy may affect metabolic outcomes in the mother and her
      offspring.

PMID- 22966096
TI  - Granulation response and partial wound closure predict healing in clinical trials
      on advanced diabetes foot ulcers treated with recombinant human epidermal growth
      factor.
AB  - OBJECTIVE: To determine if partial wound closure surrogate markers proposed for
      neuropathic, small diabetic foot ulcers (DFUs) can be extended to advanced
      lesions and if the development of granulation tissue can be used to predict
      complete healing. RESEARCH DESIGN AND METHODS: Data from two multicenter, double
      blind, randomized clinical trials (one of them placebo controlled) that used
      intralesional recombinant human epidermal growth factor (rhEGF) to promote
      granulation and healing were used. For confirmation in a larger sample from
      common clinical practice, the results of an active postmarketing surveillance of
      rhEGF treatment of DFUs in 60 healthcare units was included. The surrogates
      evaluated were percent area change, log healing rate, ratio of log areas, and
      percent of granulation tissue covering the wound area. The tests used were
      surrogate final end point correlation, receiver operating characteristic curves
      to discriminate healers from nonhealers, validation tests using logistic
      regression models, and the proportion-mediated estimation. RESULTS: Two weeks
      >50% granulation, end of treatment >75% granulation, and 16.1% area change showed
      significant predictive value (>70% correct classification) for final wound
      closure. The granulation-based variables fulfilled the criterion that the effect
      of rhEGF treatment on wound closure was mediated by the surrogate. CONCLUSIONS:
      This work provides the first evidence for the use of granulation tissue
      development as a predictor of wound healing in advanced DFUs. These results can
      be useful for clinical trial design, particularly during the exploratory phase of
      new products.

PMID- 22966097
TI  - Differential effect of glycemia on the incidence of hypertension by sex: the
      epidemiology of diabetes complications study.
AB  - OBJECTIVE: Diabetes Control and Complications Trial/Epidemiology of Diabetes
      Intervention and Complications analyses demonstrated that intensive insulin
      therapy was inversely associated with incident hypertension. We thus sought to
      confirm these observations and, given sex differences in other type 1 diabetes
      complications and risk factors, assessed whether any such associations differ by
      sex. RESEARCH DESIGN AND METHODS: Participants of a prospective cohort of
      childhood-onset type 1 diabetes, free of hypertension at study entry (baseline
      mean age, 28 years; diabetes duration, 19 years), were selected for study (n =
      510). Hypertension incidence was defined as blood pressure >140/90 mmHg or use of
      hypertension medications in two consecutive visits. Intensive insulin therapy was
      defined as three or more injections (or pump) and four or more glucose tests
      daily. Baseline predictors of hypertension were examined using Cox proportional
      hazards models. Models with time-dependent updated means of baseline significant
      variables were also constructed. RESULTS: Hypertension incidence over 18 years of
      follow-up was marginally higher in men than in women (43.2 vs. 35.4%, P = 0.07).
      A significant interaction was noted between sex and HbA(1c), and separate models
      were constructed by sex. Multivariably, elevated HbA(1c) was a significant
      predictor only in men (hazard ratio 1.48 [95% CI 1.28-1.71]). In time-dependent
      models, although a significant effect of HbA(1c) was also seen in women (1.21
      [1.00-1.46]), the effect of glycemic control on hypertension development remained
      stronger in men (1.59 [1.29-1.97], P interaction <0.0001). CONCLUSIONS: Although
      hyperglycemia is a risk factor for hypertension, its effect is stronger in men
      compared with women with type 1 diabetes.

PMID- 22966098
TI  - A population-based study of the risk of diabetic retinopathy in patients with
      type 1 diabetes and celiac disease.
AB  - OBJECTIVE: Celiac disease (CD) is associated with type 1 diabetes (T1D). In the
      current study, we examined whether CD affects the risk of diabetic retinopathy
      (DRP) in patients with T1D. RESEARCH DESIGN AND METHODS: This was a population
      based cohort study. Through the Swedish National Patient Register, we identified
      41,566 patients diagnosed with diabetes in 1964-2009 and who were <=30 years of
      age at diagnosis. CD was defined as having villous atrophy (Marsh stage 3)
      according to small intestinal biopsies performed between 1969 and 2008, with
      biopsy reports obtained from Sweden's 28 pathology departments. During follow-up,
      947 T1D patients had a diagnosis of CD. We used Cox regression analysis with CD
      as a time-dependent covariate to estimate adjusted hazard ratios (aHRs) for DRP
      in patients with T1D and CD and compared them with patients with T1D but no CD.
      RESULTS: Duration of CD correlated with the risk of DRP. When results were
      stratified by time since CD diagnosis, individuals with T1D and CD were at a
      lower risk of DRP in the first 5 years after CD diagnosis (aHR 0.57 [95% CI 0.36
      0.91]), followed by a neutral risk in years 5 to <10 (1.03 [0.68-1.57]). With
      longer follow-up, coexisting CD was a risk factor for DRP (10 to <15 years of
      follow-up, aHR 2.83 [95% CI 1.95-4.11]; >=15 years of follow-up, 3.01 [1.43
      6.32]). CONCLUSIONS: Having a diagnosis of CD for >10 years is a risk factor for
      the development of DRP in T1D. Long-standing CD in patients with T1D merits
      intense monitoring of DRP.

PMID- 22966099
TI  - Second-generation long-acting injectable antipsychotic agents: an overview.
AB  - For over 40 years, antipsychotic drugs have been used as long-term maintenance
      treatment to control symptoms and reduce relapse rates in patients with
      schizophrenia. 'First-generation' oral agents such as haloperidol and
      chlorpromazine are associated with high levels of unwanted neurological effects
      and poor rates of patient adherence.1,2 Long-acting ('depot') injections of
      antipsychotics were developed to try to improve adherence. 'Second-generation'
      antipsychotic agents (also known as atypical antipsychotics) were introduced into
      clinical practice over 16 years ago. Although these agents have a lower
      propensity to cause extrapyramidal side effects, they are associated with a range
      of other unwanted effects (e.g. weight gain and its sequelae).1,3,4 Initially,
      second-generation agents were only available as orally administered medicines.
      Three long-acting injectable formulations of second-generation antipsychotics are
      now available in the UK: olanzapine embonate injection (ZypAdhera), paliperidone
      injection (Xeplion) and risperidone injection (Risperdal Consta). In this article
      we review the evidence for these agents and discuss the practical implications of
      their use.

PMID- 22966100
TI  - Insulin pump therapy.
AB  - Insulin pump therapy makes use of an external device to deliver insulin
      continuously from a refillable storage reservoir by means of a cannula placed
      under the skin. A pump is intended to simulate pancreatic function in that it can
      be programmed to deliver an adjustable basal rate of insulin throughout the day,
      with higher infusion rates triggered by the push of a button at meal times or to
      correct a high blood glucose fluctuation. Insulin pumps have been mainly used in
      patients with type 1 diabetes. There are a number of recent technological
      innovations that support a more sophisticated approach to insulin dosing using
      insulin pumps.3 In this article we provide an overview of the use of such
      therapy.

PMID- 22966101
TI  - Extended office hours and health care expenditures: a national study.
AB  - PURPOSE: A key component of primary care improvement efforts is timely access to
      care; however, little is known regarding the effects of extended (evening and
      weekend) office hours on health care use and outcomes. We examined the
      association between reported access to extended office hours and both health care
      expenditures and mortality. METHODS: We analyzed data from individuals aged 18 to
      90 years responding to the 2000-2008 Medical Expenditure Panel Surveys reporting
      access or no access to extended hours via a usual source of care in 2 successive
      years (year 1 and year 2; N = 30,714). Dependent variables were year 2 total
      health care expenditures and, for those enrolled in 2000-2005, all-cause
      mortality through 2006. Covariates were year 1 sociodemographics and health care
      use, and year 2 health insurance, health status, and chronic conditions. We
      conducted further analyses, progressively adjusting for year 2 use, to explore
      mechanisms. RESULTS: Total expenditures were 10.4% lower (95% confidence
      interval, 7.2%-13.4%) among patients reporting access to extended hours in both
      years vs neither year. Adjustment for year 2 prescription drug expenditures, and
      to a lesser extent, office visit-related expenditures (but not total
      prescriptions or office visits, or emergency and inpatient expenditures)
      attenuated this relationship. Extended-hours access was not statistically
      associated with mortality. CONCLUSIONS: Respondents reporting a usual source of
      care offering evening and weekend office hours had lower total health care
      expenditures than those without extended-hours access, an association related to
      lower prescription drug and office visit-related (eg, testing) expenditures,
      without adverse effects on mortality. Although requiring further study, extended
      office hours may be associated with more judicious use of health care resources.

PMID- 22966102
TI  - Estimating a reasonable patient panel size for primary care physicians with team
      based task delegation.
AB  - PURPOSE Primary care faces the dilemma of excessive patient panel sizes in an
      environment of a primary care physician shortage. We aimed to estimate primary
      care panel sizes under different models of task delegation to nonphysician
      members of the primary care team.  METHODS We used published estimates of the
      time it takes for a primary care physician to provide preventive, chronic, and
      acute care for a panel of 2,500 patients, and modeled how panel sizes would
      change if portions of preventive and chronic care services were delegated to
      nonphysician team members.  RESULTS Using 3 assumptions about the degree of task
      delegation that could be achieved (77%, 60%, and 50% of preventive care, and 47%,
      30%, and 25% of chronic care), we estimated that a primary care team could
      reasonably care for a panel of 1,947, 1,523, or 1,387 patients.  CONCLUSIONS If
      portions of preventive and chronic care services are delegated to nonphysician
      team members, primary care practices can provide recommended preventive and
      chronic care with panel sizes that are achievable with the available primary care
      workforce.

PMID- 22966103
TI  - Influence of primary care on breast cancer outcomes among Medicare beneficiaries.
AB  - PURPOSE: We used the Surveillance Epidemiology and End Results (SEER)-Medicare
      database to explore the association between primary care and breast cancer
      outcomes. METHODS: Using a retrospective cohort study of 105,105 female Medicare
      beneficiaries with a diagnosis of breast cancer in SEER registries during the
      years 1994-2005, we examined the total number of office visits to primary care
      physicians and non-primary care physicians in a 24-month period before cancer
      diagnosis. For women with invasive cancers, we examined the odds of diagnosis of
      late-stage disease, according to the American Joint Commission on Cancer (AJCC)
      (stages III and IV vs stages I and II), and survival (breast cancer specific and
      all cause) using logistic regression and proportional hazards models,
      respectively. We also explored whether including noninvasive cancers, such as
      ductal carcinoma in situ (DCIS), would alter results and whether prior
      mammography was a potential mediator of associations. RESULTS: Primary care
      physician visits were associated with improved breast cancer outcomes, including
      greater use of mammography, reduced odds of late-stage diagnosis, and lower
      breast cancer and overall mortality. Prior mammography (and resultant earlier
      stage diagnosis) mediated these associations in part, but not completely. Similar
      results were seen for non-primary care physician visits. Results were similar
      when women with DCIS were included in the analysis. CONCLUSIONS: Medicare
      beneficiaries with breast cancer had better outcomes if they made greater use of
      a primary care physician's ambulatory services. These findings suggest adequate
      primary medical care may be an important factor in achieving optimal breast
      cancer outcomes.

PMID- 22966104
TI  - Program to improve colorectal cancer screening in a low-income, racially diverse
      population: a randomized controlled trial.
AB  - PURPOSE More effective strategies are needed to improve rates of colorectal
      cancer screening, particularly among the poor, racial and ethnic minorities, and
      individuals with limited English proficiency. We examined whether the direct
      mailing of fecal occult blood testing (FOBT) kits to patients overdue for such
      screening is an effective way to improve screening in this population.  METHODS
      All adults aged 50 to 80 years who did not have documentation of being up to date
      with colorectal cancer screening as of December 31, 2009, and who had had at
      least 2 visits to the community health center in the prior 18 months were
      randomized to the outreach intervention or usual care. Patients in the outreach
      group were mailed a colorectal cancer fact sheet and FOBT kit. Patients in the
      usual care group could be referred for screening during usual clinician visits.
      The primary outcome was completion of colorectal cancer screening (by FOBT,
      sigmoidoscopy, or colonoscopy) 4 months after initiation of the outreach
      protocol. Outcome measures were compared using the Fisher exact test.  RESULTS
      Analyses were based on 104 patients assigned to the outreach intervention and 98
      patients assigned to usual care. In all, 30% of patients in the outreach group
      completed colorectal cancer screening during the study period, compared with 5%
      of patients in the usual care group (P <.001). Nearly all of the screenings were
      by FOBT. The groups did not differ significantly with respect to the percentage
      of patients making a clinician visit or the percentage for whom a clinician
      placed an order for a screening test.  CONCLUSIONS The mailing of FOBT kits
      directly to patients was efficacious for promoting colorectal cancer screening
      among a population with high levels of poverty, limited English proficiency, and
      racial and ethnic diversity. Non-visit-based outreach to patients may be an
      important strategy to address suboptimal rates of colorectal cancer screening
      among populations most at risk for not being screened.

PMID- 22966105
TI  - Adult cancer survivors discuss follow-up in primary care: 'not what i want, but
      maybe what i need'.
AB  - BACKGROUND Nearly one-third of office visits for cancer are handled by primary
      care physicians. Yet, few studies examine patient perspectives on these
      physicians' roles in their cancer follow-up care or their care preferences. 
      METHODS We explored survivor preferences through qualitative, semistructured, in
      depth interviews drawing on patients recruited from 2 National Cancer Institute
      designated comprehensive cancer centers and 6 community hospitals. We recruited a
      purposive sample of early-stage breast and prostate cancer survivors aged 47 to
      80 years, stratified by age, race, and length of time from and location of cancer
      treatment. Survivors were at least 2 years beyond completion of their active
      cancer treatment  RESULTS Forty-two survivors participated in the study. Most
      participants expressed strong preferences to receive follow-up care from their
      cancer specialists (52%). They described the following barriers to the primary
      care physician's engagement in follow-up care: (1) lack of cancer expertise, (2)
      limited or no involvement with original cancer care, and (3) lack of care
      continuity. Only one-third of participants (38%) believed there was a role for
      primary care in cancer follow-up care and suggested the following opportunities:
      (1) performing routine cancer-screening tests, (2) supplementing cancer and
      cancer-related specialist care, and (3) providing follow-up medical care when
      "enough time has passed" or the survivors felt that they could reintegrate into
      the noncancer population.  CONCLUSION Survivors have concerns about seeing their
      primary care physician for cancer-related follow-up care. Research interventions
      to address these issues are necessary to enhance the quality of care received by
      cancer survivors.

PMID- 22966106
TI  - Health care consumers' preferences around health information exchange.
AB  - PURPOSE Consumer buy-in is important for the success of widespread federal
      initiatives to promote the use of health information exchange (HIE). Little is
      known, however, of consumers' preferences around the storing and sharing of
      electronic health information. We conducted a study to better understand consumer
      preferences regarding the privacy and security of HIE.  METHODS In 2008 we
      conducted a cross-sectional, random digit dial telephone survey of residents in
      the Hudson Valley of New York State, a state where patients must affirmatively
      consent to having their data accessed through HIE.  RESULTS There was an 85%
      response rate (N = 170) for the survey. Most consumers would prefer that
      permission be obtained before various parties, including their clinician, could
      view their health information through HIE. Most consumers wanted any method of
      sharing their health information to have safeguards in place to protect against
      unauthorized viewing (86%). They also wanted to be able to see who has viewed
      their information (86%), to stop electronic storage of their data (84%), to stop
      all viewing (83%), and to select which parts of their health information are
      shared (78%). Among the approximately one-third (n = 54) of consumers who were
      uncomfortable with automatic inclusion of their health information in an
      electronic database for HIE, 78% wished to approve all information explicitly,
      and most preferred restricting information by clinician (83%), visit (81%), or
      information type (88%).  CONCLUSION Consumers in a state with an opt-in consent
      policy are interested in having greater control over the privacy and security of
      their electronic health information. These preferences should be considered when
      developing and implementing systems, standards and policies.

PMID- 22966107
TI  - Trajectories of psychological distress after stroke.
AB  - PURPOSE: There has been little exploration of the distinct trajectories of
      psychological distress after stroke and the factors that predict recovery from
      distress. These trajectories may assist primary care physicians by providing
      insight into disease onset, progression, and resolution and may be a useful way
      to conceptualize and understand the pattern of psychological morbidity in stroke
      over time. We undertook a longitudinal qualitative study to explore poststroke
      psychological trajectories METHODS: The primary data collection method was
      semistructured interviews with community-dwelling stroke survivors in
      metropolitan Newcastle, New South Wales, Australia. Our sample included 23
      participants (12 men, 10 women; age range 37 to 94 years) discharged from a
      tertiary referral hospital after a stroke; these participants subsequently
      participated in a total of 106 interviews over 12 months. Qualitative outcomes
      were participants' perceptions at baseline, 3, 6, 9, and 12 months. Thematic
      saturation was achieved. RESULTS: Most participants were male (54%) and had a
      partial anterior circulation infarction stroke subtype (57%). Four different
      longitudinal trajectories were identified: resilience (n = 5); ongoing crisis (n
      = 5), emergent mood disturbance (n = 3), and recovery from mood disturbance (n =
      10). Recovery from mood disturbance was facilitated by gains in independence and
      self-esteem and by having an internal health locus of control. CONCLUSIONS:
      Stroke survivors experienced a variety of psychological trajectories. Identifying
      distinct trajectories of psychological morbidity may help primary care physicians
      develop appropriately timed interventions to promote better mental health.
      Interventions require implementation over a longer duration than the current
      outpatient services that, in Australia, are typically provided in the first few
      months after stroke.

PMID- 22966108
TI  - Validation of a generic measure of continuity of care: when patients encounter
      several clinicians.
AB  - PURPOSE: Patients who regularly see more than one clinician for health problems
      risk discontinuity and fragmented care. Our objective was to develop and validate
      a generic measure of management continuity from the patient perspective. METHODS:
      Themes from 33 qualitative studies of patient experience with care from various
      clinicians were matched to existing instruments to identify potential measures
      and measurement gaps. Adapted and new items were tested cognitively, and the
      instrument was administered to 376 adult patients consulting in primary care for
      a variety of health conditions but seeing clinicians in a variety of settings.
      After initial psychometric analysis, the instrument was modified slightly and
      readministered after 6 months. The analysis identified reliable subscales and
      their association with indicators of continuity. RESULTS: Observed factors
      correspond to 8 intended constructs, with good reliability. Three subscales (12
      items) relate to the principal clinician and cover management and relational
      continuity. Four subscales (13 items) are related to multiple clinicians and
      address team relational continuity and problems with coordination and gaps in
      information transfer. Two (11 items) pertain to the patient's partnership in
      care. Subscales correlate well and in expected directions with indicators of
      discontinuity (wanting to change clinicians, suffering, and sense of being
      abandoned, medical errors) and degree of care organization. CONCLUSION: The
      instrument reliably assesses both positive and negative dimensions of continuity
      of care across the entire system, and the subscales correlate with continuity
      effects. It supports patient-centered and relationship-based care and can be used
      as a whole or in part to assess coordination and continuity in primary care.

PMID- 22966109
TI  - The changing face of chronic illness management in primary care: a qualitative
      study of underlying influences and unintended outcomes.
AB  - PURPOSE: Recently, there has been dramatic increase in the diagnosis and
      pharmaceutical management of common chronic illnesses. Using qualitative data
      collected in primary care clinics, we assessed how these trends play out in
      clinical care. METHODS: This qualitative study focused on management of type 2
      diabetes and hypertension in 44 primary care clinics in Michigan and was based on
      interviews with 58 clinicians and 70 of their patients, and observations of 107
      clinical consultations. We assessed clinicians' treatment strategies and
      discussions of factors influencing treatment decisions, and patients'
      understandings and experiences in managing these illnesses. RESULTS: Clinicians
      focused on helping patients achieve test results recommended by national
      guidelines, and most reported combining 2 or more medications per condition to
      reach targets. Medication selection and management was the central focus of the
      consultations we observed. Polypharmacy was common among patients, with more than
      one-half taking 5 or more medications. Patient interviews indicated that heavy
      reliance on pharmaceuticals presents challenges to patient well-being, including
      financial costs and experiences of adverse health effects. CONCLUSIONS: Factors
      promoting heavy use of pharmaceuticals include lower diagnostic and treatment
      thresholds, clinician-auditing and reward systems, and the prescribing cascade,
      whereby more medications are prescribed to control the effects of already
      prescribed medications. We present a conceptual model, the inverse benefit law,
      to provide insight into the impact of pharmaceutical marketing efforts on the
      observed trends. We make recommendations about limiting the influence of the
      pharmaceutical industry on clinical practice, toward improving the well-being of
      patients with chronic illness.

PMID- 22966111
TI  - STFM collaborates with PAEA to promote interprofessional education.

PMID- 22966110
TI  - Pay-for-performance in the United Kingdom: impact of the quality and outcomes
      framework: a systematic review.
AB  - PURPOSE: Primary care practices in the United Kingdom have received substantial
      financial rewards for achieving standards set out in the Quality and Outcomes
      Framework since April 2004. This article reviews the growing evidence for the
      impact of the framework on the quality of primary medical care. METHODS: Five
      hundred seventy-five articles were identified by searching the MEDLINE, EMBASE,
      and PsycINFO databases, and from the reference lists of published reviews and
      articles. One hundred twenty-four relevant articles were assessed using a
      modified Downs and Black rating scale for 110 observational studies and a
      Critical Appraisal Skills Programme rating scale for 14 qualitative studies.
      Ninety-four studies were included in the review. RESULTS: Quality of care for
      incentivized conditions during the first year of the framework improved at a
      faster rate than the preintervention trend and subsequently returned to prior
      rates of improvement. There were modest cost-effective reductions in mortality
      and hospital admissions in some domains. Differences in performance narrowed in
      deprived areas compared with nondeprived areas. Achievement for conditions
      outside the framework was lower initially and has worsened in relative terms
      since inception. Some doctors reported improved data recording and teamwork, and
      nurses enhanced specialist skills. Both groups believed that the person
      centeredness of consultations and continuity were negatively affected. Patients'
      satisfaction with continuity declined, with little change in other domains of
      patient experience. CONCLUSIONS: Observed improvements in quality of care for
      chronic diseases in the framework were modest, and the impact on costs,
      professional behavior, and patient experience remains uncertain. Further research
      is needed into how to improve quality across different domains, while minimizing
      costs and any unintended adverse effects of payment for performance schemes.
      Health care organizations should remain cautious about the benefits of similar
      schemes.

PMID- 22966112
TI  - ADFM's mission, vision, and goals: foundation of our new 3-year strategic plan.

PMID- 22966113
TI  - Primary care payment reform: the missing link.

PMID- 22966114
TI  - Large data sets in primary care research.

PMID- 22966115
TI  - AAFP position paper opposes mandated cme, other barriers for prescribers of
      opioids.

PMID- 22966116
TI  - The phylogenetic significance of the carpophore in Apiaceae.
AB  - BACKGROUND AND AIMS: Fruit structural characters have traditionally been
      important in the taxonomy of the family Apiaceae. Previous investigations using a
      limited number of taxa have shown that the carpophore may be especially useful in
      helping to circumscribe subfamily Azorelloideae. The present study examines, for
      the first time, carpophore structure in 92 species from 43 genera, representing
      all subfamilies of Apiaceae, and including all genera assigned to subfamily
      Azorelloideae. Phylogenetic interpretations are made for the first time, using
      all available information, and a standard terminology is proposed to describe the
      various character states found in carpophores. METHODS: Carpophore structure was
      studied in detail using light microscopy. KEY RESULTS: Carpophores, when present,
      may be categorized into two main groups (B and C) based mainly on the arrangement
      of the vascular bundles in transverse section, and further divided into six sub
      types according to the length of the carpophore (short in B1 and C1) and whether
      they are entire (B1-B3 and C1) or bifurcate (B4 and C2). Free carpophores are
      absent in subfamily Mackinlayoideae, and in tribes Lichtensteinieae and
      Phlyctidocarpeae, which have two opposite vascular bundles (Group A). Entire
      carpophores with one or two vascular bundles, or bifurcate carpophores with
      lateral vascular bundles (arranged side by side within the commissural plane),
      are the main types characterizing Azorelloideae. The short, hygroscopic
      carpophores found in Choritaenia are unique in Apiaceae and provide additional
      evidence for the exclusion of this genus from Azorelloideae. Carpophore type C2
      is typical for most Apioideae sensu lato (exceptions are, for example, Arctopus
      and Alepidea, which have type B2). CONCLUSIONS: A single carpophore and ventral
      vascular bundles not forming free carpophores are proposed to be the ancestral
      conditions in Apiaceae, while bifurcate carpophores with opposite vascular
      bundles are the derived state, present in most Apioideae. Secondary reductions
      seem to have occurred in several unrelated lineages in all major groups, e.g.
      many Azorelloideae, several protoapioids (including nearly all members of the
      tribe Saniculeae) and 29 euapioid genera (e.g. some Oenantheae).

PMID- 22966117
TI  - Immunological evidence of incipient pulmonary tuberculosis.

PMID- 22966120
TI  - Surfactant protein A blocks recognition of Pseudomonas aeruginosa by CKAP4/P63 on
      airway epithelial cells.
AB  - We used isogenic mutant strains that were deficient or over-expressed capsule to
      study the function of the alginate exopolysaccharide in the interaction of
      Pseudomonas aeruginosa with the human airway epithelial cells (AEC) in the
      presence or absence of surfactant protein A (SP-A). SP-A prevented the invasion
      of AEC by alginate-producing P. aeruginosa strains because of a direct effect on
      the AEC. Monoclonal antibodies to CKAP4/P63, the principal SP-A-binding receptor
      on AEC, or inhibition of its expression using specific siRNA reduced the invasion
      of both highly encapsulated and poorly encapsulated strains, but not the invasion
      of the acapsular mutant. Treatment of AEC with SP-A, monoclonal antibodies to
      CKAP4/P63, or CKAP4/P63-specific siRNA decreased the binding of purified alginate
      exopolysaccharide to AEC. Alginate binding to AEC reduced SP-A release by these
      cells. Because the alginate exopolysaccharide is surface-exposed, levels of SP-A
      may be crucial to modulate the interaction of P. aeruginosa with AEC.

PMID- 22966121
TI  - Mucosal Escherichia coli bactericidal activity and immune mediators are
      associated with HIV-1 seroconversion in women participating in the HPTN 035
      trial.
AB  - The mucosal environment may impact the risk for human immunodeficiency virus type
      1 (HIV-1) acquisition. Immune mediators were measured in vaginal fluid collected
      from HPTN 035 participants who acquired HIV-1 and from those who remained HIV-1
      negative (controls). Mediator concentrations were similar in samples obtained
      before as compared to after HIV-1 acquisition in the 8 seroconverters. Compared
      with controls, seroconverters were more likely to have detectable levels of
      HbetaD-2 (odds ratio [OR], 2.39; P = .005) and greater Escherichia coli
      bactericidal activity (OR, 1.22; P = .01) prior to seroconversion. E. coli
      bactericidal activity remained significant in a multivariable analysis (P = .02)
      and may be a biomarker for HIV-1 acquisition.

PMID- 22966119
TI  - Genetic relatedness of infecting and reinfecting respiratory syncytial virus
      strains identified in a birth cohort from rural Kenya.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) reinfects individuals repeatedly.
      The extent to which this is a consequence of RSV antigenic diversity is unclear.
      METHODS: Six-hundred thirty-five children from rural Kenya were closely monitored
      for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections
      were identified by immunofluorescence testing of nasal washing samples collected
      during acute respiratory illnesses, typed into group A and B, and sequenced in
      the attachment (G) protein. A positive sample separated from a previous positive
      by >=14 days was defined as a reinfection a priori. RESULTS: Phylogenetic
      analysis was undertaken for 325 (80%) of 409 identified infections, including 53
      (64%) of 83 reinfections. Heterologous group reinfections were observed in 28
      episodes, and homologous group reinfections were observed in 25 episodes; 10
      involved homologous genotypes, 5 showed no amino acid changes, and 3 were
      separated by 21-24 days and were potentially persistent infections. The temporal
      distribution of genotypes among reinfections did not differ from that of single
      infections. CONCLUSIONS: The vast majority of infection and reinfection pairs
      differed by group, genotype, or G amino acid sequence (ie, comprised distinct
      viruses). The extent to which this is a consequence of immune memory of infection
      history or prevalent diversity remains unclear.

PMID- 22966122
TI  - Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug
      therapy with subsequent selection and transmission.
AB  - A small proportion (1%-1.5%) of 2009 pandemic influenza A/H1N1 virus strains
      (A[H1N1]pdm09) are oseltamivir resistant, almost exclusively because of a H275Y
      mutation in the neuraminidase protein. However, many individuals infected with
      resistant strains had not received antivirals. Whether drug-resistant viruses are
      initially present as minor variants in untreated individuals before they emerge
      as the dominant strain in a virus population is of great importance for
      predicting the speed at which resistance will arise. To address this issue, we
      used ultra-deep sequencing of viral populations from serial nasopharyngeal
      specimens from an immunocompromised child and from 2 individuals in a household
      outbreak. We observed that the Y275 mutation was present as a minor variant in
      infected hosts before the onset of therapy. We also found evidence for the
      transmission of this drug-resistant variant with drug-susceptible viruses. These
      observations provide important information on the relative fitness of the Y275
      mutation in the absence of oseltamivir treatment.

PMID- 22966123
TI  - Risk factors for efflux pump overexpression in fluoroquinolone-resistant
      Escherichia coli.
AB  - BACKGROUND: We conducted a case-control study to identify risk factors for efflux
      overexpression, an important mechanism of fluoroquinolone resistance, among
      patients with fluoroquinolone-resistant Escherichia coli (FQREC) gastrointestinal
      tract colonization. METHODS: Three annual fecal surveillance surveys were
      performed hospital-wide, and all patients colonized with FQREC (levofloxacin
      minimum inhibitory concentration, >=8 MUg/mL) were included in the study. Cases
      and controls were defined on the basis of overexpression of the AcrAB efflux
      pump, as measured by the organic solvent tolerance (OST) assay. A multivariable
      logistic regression model was developed to identify risk factors for OST
      positivity among patients with FQREC colonization. RESULTS: Eighty-nine patients
      were colonized with FQREC: 44 (49.4%) and 45 (50.6%) patients had isolates that
      were OST-positive and OST-negative, respectively. On multivariable analyses,
      location on the surgical service was significantly associated with recovery of an
      OST-positive isolate (odds ratio, 7.36; 95% confidence interval, 1.82-29.7; P =
      .005). Furthermore, patients who had received a first-generation cephalosporin in
      the 30 days prior to sampling were less likely to have an OST-positive isolate
      (odds ratio, 0.20; 95% confidence interval, .04-.94; P = .04). CONCLUSIONS: Among
      phenotypically identical FQREC isolates, different factors may drive the
      emergence of different resistance mechanisms. Further studies are needed to
      elucidate the relationship between antimicrobial use and specific resistance
      mechanisms.

PMID- 22966124
TI  - Relapses contribute significantly to the risk of Plasmodium vivax infection and
      disease in Papua New Guinean children 1-5 years of age.
AB  - BACKGROUND: Plasmodium vivax forms long-lasting hypnozoites in the liver. How
      much they contribute to the burden of P. vivax malaria in children living in
      highly endemic areas is unknown. METHODS: In this study, 433 Papua New Guinean
      children aged 1-5 years were Randomized to receive artesunate (7 days) plus
      primaquine (14 days), artesunate alone or no treatment and followed up actively
      for recurrent Plasmodium infections and disease for 40 weeks. RESULTS: Treatment
      with artesunate-primaquine reduced the risk of P. vivax episodes by 28% (P =
      .042) and 33% (P = .015) compared with the artesunate and control arms,
      respectively. A significant reduction was observed only in the first 3 months of
      follow-up (artesunate-primaquine vs control, -58% [P = .004]; artesunate
      primaquine vs artesunate, -49% [P = .031]) with little difference thereafter.
      Primaquine treatment also reduced the risk of quantitative real-time polymerase
      chain reaction- and light microscopy-positive P. vivax reinfections by 44% (P <
      .001) and 67% (P < .001), respectively. Whereas primaquine treatment did not
      change the risk of reinfection with Plasmodium falciparum, fewer P. falciparum
      clinical episodes were observed in the artesunate-primaquine arm. CONCLUSIONS:
      Hypnozoites are an important source of P. vivax infection and contribute
      substantially to the high burden of P. vivax disease observed in young Papua New
      Guinean children. Even in highly endemic areas with a high risk of reinfection,
      antihypnozoite treatment should be given to all cases with parasitologically
      confirmed P. vivax infections.

PMID- 22966125
TI  - Young chronic hepatitis B patients with nucleos(t)ide analogue-induced hepatitis
      B e antigen seroconversion have a higher risk of HBV reactivation.
AB  - BACKGROUND: It is unclear whether hepatitis B e antigen (HBeAg) seroconversion
      induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that
      of spontaneous HBeAg seroconversion. METHODS: A total of 148 noncirrhotic NUC
      induced HBeAg seroconverters were consecutively enrolled. A historical control of
      407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared
      the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts.
      RESULTS: There were 1652.8 and 465.2 person-years of follow-up for spontaneous
      and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced
      seroconverters, spontaneous seroconverters were younger when achieving HBeAg
      seroconversion. We thus compared these 2 cohorts according to their age at HBeAg
      seroconversion. In patients achieving HBeAg seroconversion before 30 years of
      age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than
      spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of
      HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using
      multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of
      both endpoints in young HBeAg seroconverters. CONCLUSION: NUC-induced HBeAg
      seroconverters may not have durable response after stopping therapy. For patients
      achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg
      seroreversion and HBV reactivation is higher in NUC-induced seroconverters than
      spontaneous HBeAg seroconverters.

PMID- 22966126
TI  - New insights into acquisition, boosting, and longevity of immunity to malaria in
      pregnant women.
AB  - BACKGROUND: How antimalarial antibodies are acquired and maintained during
      pregnancy and boosted after reinfection with Plasmodium falciparum and Plasmodium
      vivax is unknown. METHODS: A nested case-control study of 467 pregnant women (136
      Plasmodium-infected cases and 331 uninfected control subjects) in northwestern
      Thailand was conducted. Antibody levels to P. falciparum and P. vivax merozoite
      antigens and the pregnancy-specific PfVAR2CSA antigen were determined at
      enrollment (median 10 weeks gestation) and throughout pregnancy until delivery.
      RESULTS: Antibodies to P. falciparum and P. vivax were highly variable over time,
      and maintenance of high levels of antimalarial antibodies involved highly dynamic
      responses resulting from intermittent exposure to infection. There was evidence
      of boosting with each successive infection for P. falciparum responses,
      suggesting the presence of immunological memory. However, the half-lives of
      Plasmodium antibody responses were relatively short, compared with measles (457
      years), and much shorter for merozoite responses (0.8-7.6 years), compared with
      PfVAR2CSA responses (36-157 years). The longer half-life of antibodies to
      PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to
      protect subsequent pregnancies. CONCLUSIONS: These findings may have important
      practical implications for predicting the duration of vaccine-induced responses
      by candidate antigens and supports the development of malaria vaccines to protect
      pregnant women.

PMID- 22966127
TI  - Changes in Anopheles funestus biting behavior following universal coverage of
      long-lasting insecticidal nets in Benin.
AB  - BACKGROUND: Behavioral modification of malaria vectors in response to vector
      control methods is of great concern. We investigated whether full coverage of
      long-lasting insecticide-treated mosquito nets (LLINs) may induce a switch in
      biting behavior in Anopheles funestus, a major malaria vector in Africa. METHODS:
      Human-landing collections were conducted indoor and outdoor in 2 villages
      (Lokohoue and Tokoli) in Benin before and 1 year and 3 years after implementation
      of universal LLIN coverage. Proportion of outdoor biting (POB) and median
      catching times (MCT) were compared. The resistance of A. funestus to deltamethrin
      was monitored using bioassays. RESULTS: MCT of A. funestus switched from 2 AM in
      Lokohoue and 3 AM in Tokoli to 5 AM after 3 years (Mann-Whitney U test, P <
      .0001). In Tokoli, POB increased from 45% to 68.1% (odds ratio = 2.55; 95
      confidence interval = 1.72-3.78; P < .0001) 1 year after the universal coverage,
      whereas POB was unchanged in Lokohoue. In Lokohoue, however, the proportion of A.
      funestus that bites after 6 am was 26%. Bioassays showed no resistance to
      deltamethrin. CONCLUSIONS: This study provides evidence for a switch in malaria
      vectors' biting behavior after the implementation of LLIN at universal coverage.
      These findings might have direct consequences for malaria control in Africa and
      highlighted the need for alternative strategies for better targeting malaria
      vectors.

PMID- 22966128
TI  - Elevated serum interleukin-10 at time of hospital admission is predictive of
      mortality in patients with Staphylococcus aureus bacteremia.
AB  - BACKGROUND: Staphylococcus aureus bacteremia (SaB) carries considerable morbidity
      and mortality. We examined the predictive value of serum concentrations of
      interleukin (IL)-10, proinflammatory cytokines, and terminal complement on
      patient survival and SaB duration. METHODS: Clinical information on consecutive
      patients with SaB at a tertiary medical center were collected prospectively.
      Patient serum samples obtained at the day of clinical presentation were assayed
      for tumor necrosis factor-alpha, IL-1beta, IL-10, and complement membrane attack
      complex C5b-9 concentrations using enzyme-linked immunoassay. Logistic regression
      identified predictors of mortality and duration of bacteremia. RESULTS: In 59
      patients with SaB, 14% died and 17% had prolonged bacteremia (>4 days). Elevated
      IL-10 serum concentrations (>7.8 pg/mL) identified all 8 patients who died,
      whereas there were no deaths in patients with normal IL-10 (P = .016). The lack
      of an IL-1beta response (<=0.45 pg/mL) defined all patients with SaB >4 days. In
      multivariate analysis, patient age (odds ratio [OR], 1.16; P = .022), duration of
      bacteremia (OR, 1.16; P = .031), and serum IL-10 (OR, 1.05; P = .014) were
      identified as independent predictors of patient mortality. CONCLUSIONS: SaB
      mortality was confined strictly to patients with elevated IL-10 concentrations.
      We recommend that future clinical trials of SaB stratify patients according to IL
      10 and IL-1beta serum concentrations in order to better evaluate the impact of
      therapeutic interventions on patient outcome.

PMID- 22966129
TI  - Waning antibody levels and avidity: implications for MMR vaccine-induced
      protection.
AB  - BACKGROUND: The measles-mumps-rubella (MMR) vaccine is effective in eliciting a
      good antibody response. In addition to the amount of antibodies, the avidity of
      these antibodies might be important in protecting against disease. METHODS: The
      amount of circulating antibodies for measles, mumps, and rubella was measured
      with enzyme immunoassays, and the avidity of these antibodies was determined by
      urea dissociation. Three groups of twice-MMR-vaccinated individuals and 1 group
      of naturally infected individuals were studied. One vaccinated group (n = 71) was
      studied 6 months and 20 years after a second MMR vaccination. RESULTS: The
      antibody avidity indexes were high for measles and rubella but low for mumps.
      Twenty years after a second MMR vaccination, antibody levels for all 3 viruses
      waned. Also, the mean avidity index decreased by 8% for measles, 24% for mumps,
      and remained unchanged for rubella. Antibody avidity correlated with antibody
      concentration for measles. There was partial correlation for rubella and no
      correlation for mumps. CONCLUSIONS: Measles and rubella induced high-avidity
      antibodies and mumps induced low-avidity antibodies after both vaccination and
      natural infection. Waning of both the concentration as well as the avidity of
      antibodies might contribute to measles and mumps infections in twice-MMR
      vaccinated individuals.

PMID- 22966131
TI  - The mannose receptor.
AB  - The MR is a highly effective endocytic receptor with a broad binding specificity
      encompassing ligands of microbial and endogenous origin and a poorly
      characterized ability to modulate cellular activation. This review provides an
      update of the latest developments in the field. It discusses how MR biology might
      be affected by glycosylation and proteolytic processing, MR involvement in
      antigen delivery, and the potential contribution of MR to T cell differentiation
      and cellular activation. Further understanding of these areas will, no doubt,
      inform the design of novel, therapeutic tools for improved vaccination, control
      of inflammation, and tumor chemotherapy, which will benefit from exploiting MR
      efficient internalization properties and unique pattern of expression.

PMID- 22966130
TI  - Vaccination with a UV-irradiated genetically attenuated mutant of Staphylococcus
      aureus provides protection against subsequent systemic infection.
AB  - Staphylococcus aureus are gram-positive bacteria that cause clinically
      significant infections in humans. Severe S. aureus infections are particularly
      problematic in hospitalized patients and reoccur despite therapeutic measures.
      The absence of natural protective immune responses and the lack of high
      throughput approaches to identify S. aureus antigens have imposed constraints in
      the development of effective vaccines. Here, we showed that vaccination with the
      genetically attenuated S. aureus mutant, inactivated using UV irradiation rather
      than heat, significantly increased survival and diminished bacterial burden and
      kidney abscesses when mice were challenged with virulent methicillin-sensitive or
      methicillin-resistant S. aureus. Protection conferred by immunization could be
      transferred to the naive host and was not observed in B-cell-deficient mice.
      Using a novel S. aureus whole-proteome microarray, we show that immunoglobulin G
      antibody responses to 83 proteins were observed in the immunized mice. These
      results suggest that protection against S. aureus infections requires antibody
      responses to the wide repertoire of antigens/virulence factors. Vaccination using
      UV-irradiated genetically attenuated S. aureus induces humoral immunity and
      provides a vaccine strategy for pathogens that fail to induce protective
      immunity. We also describe a novel, high-throughput technology to easily identify
      S. aureus antigens for vaccine development.

PMID- 22966132
TI  - Neuroactive steroids, their metabolites, and neuroinflammation.
AB  - Neuroinflammation represents a common feature of many neurodegenerative diseases
      implicated both in their onset and progression. Neuroactive steroids act as
      physiological regulators and protective agents in the nervous system. Therefore,
      the attention of biomedical research has been recently addressed in evaluating
      whether neuroactive steroids, such as progestagens, androgens, and estrogens may
      also affect neuroinflammatory pathways. Observations so far obtained suggest a
      general anti-inflammatory effect with a beneficial relapse on several
      neurodegenerative experimental models, thus confirming the potentiality of a
      neuroprotective strategy based on neuroactive steroids. In this scenario,
      neuroactive steroid metabolism and the sophisticated machinery involved in their
      signaling are becoming especially attractive. In particular, because metabolism
      of neuroactive steroids as well as expression of their receptors is affected
      during the course of neurodegenerative events, a crucial role of progesterone and
      testosterone metabolites in modulating neuroinflammation and neurodegeneration
      may be proposed. In the present review, we will address this issue, providing
      evidence supporting the hypothesis that the efficacy of neuroactive steroids
      could be improved through the use of their metabolites.

PMID- 22966134
TI  - Caffeine occupancy of human cerebral A1 adenosine receptors: in vivo
      quantification with 18F-CPFPX and PET.
AB  - Caffeine is the neuroactive agent in coffee and tea and is a broadly consumed
      stimulant. It is a nonselective antagonist of the neuromodulator adenosine and,
      if applied in commonly consumed doses, evokes its stimulating effects through the
      blockade of adenosine receptors. (18)F-8-cyclopentyl-3-(3-fluoropropyl)-1
      propylxanthine ((18)F-CPFPX) has been established as a highly selective and
      affine PET ligand for the A(1) adenosine receptor (A(1)AR). The objective of the
      present study was to visualize and quantify the in vivo occupancy of the human
      cerebral A(1)AR by caffeine using (18)F-CPFPX and PET. METHODS: Fifteen subjects
      (age range, 24-68 y) underwent a 140-min bolus-plus-constant-infusion PET
      experiment after at least 36 h of caffeine abstinence. Metabolite-corrected blood
      data were used to calculate steady-state distribution volumes (V(T)) during the
      baseline condition of the scan between 70 and 90 min. Subsequently, subjects
      received a 10-min infusion of varying concentrations (0.5-4.3 mg/kg of body
      weight) of caffeine at 90 min. Occupancy V(T) of the A(1)AR was thereafter
      estimated using data acquired between 120 and 140 min. Occupancy levels were
      calculated using the Lassen plot, from which the inhibitory concentrations of 50%
      were derived. Plasma levels of caffeine were determined at regular intervals. One
      subject received an intravenous vehicle as a placebo. RESULTS: Caffeine displaced
      5%-44% of (18)F-CPFPX binding in a concentration-dependent manner. There was no
      change of radioligand binding after the administration of placebo. Half-maximal
      displacement was achieved at a plasma caffeine concentration of 67 MUM, which
      corresponds to 450 mg in a 70-kg subject or approximately 4.5 cups of coffee.
      CONCLUSION: Given a biologic half-life of about 5 h, caffeine might therefore
      occupy up to 50% of the cerebral A(1)AR when caffeinated beverages are repeatedly
      consumed during a day. Furthermore, the present study provides evidence that
      (18)F-CPFPX PET is suitable for studying the cerebral actions of caffeine, the
      most popular neurostimulant worldwide.

PMID- 22966135
TI  - Disease invasion: impacts on biodiversity and human health.
AB  - An introduction to the theme issue that includes papers that identify how, where
      and why infectious diseases in wildlife emerge, while also addressing their
      possible conservation impacts.

PMID- 22966133
TI  - Multiple roles of COUP-TFII in cancer initiation and progression.
AB  - Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an
      orphan nuclear receptor that acts as a transcriptional activator or repressor in
      a cell type-dependent manner. Best characterized for its role in the regulation
      of angiogenesis during mouse development, COUP-TFII also plays important roles in
      glucose metabolism and cancer. Expression of COUP-TFII is altered in various
      endocrine conditions. Cell type-specific functions and the regulation of COUP
      TFII expression result in its varying physiological and pathological actions in
      diverse systems. Evidence will be reviewed for oncogenic and tumor-suppressive
      functions of COUP-TFII, with roles in angiogenesis, metastasis, steroidogenesis,
      and endocrine sensitivity of breast cancer described. The applicability of
      current data to our understanding of the role of COUP-TFII in cancer will be
      discussed.

PMID- 22966136
TI  - Linking community and disease ecology: the impact of biodiversity on pathogen
      transmission.
AB  - The increasing number of zoonotic diseases spilling over from a range of wild
      animal species represents a particular concern for public health, especially in
      light of the current dramatic trend of biodiversity loss. To understand the
      ecology of these multi-host pathogens and their response to environmental
      degradation and species extinctions, it is necessary to develop a theoretical
      framework that takes into account realistic community assemblages. Here, we
      present a multi-host species epidemiological model that includes empirically
      determined patterns of diversity and composition derived from community ecology
      studies. We use this framework to study the interaction between wildlife
      diversity and directly transmitted pathogen dynamics. First, we demonstrate that
      variability in community composition does not affect significantly the intensity
      of pathogen transmission. We also show that the consequences of community
      diversity can differentially impact the prevalence of pathogens and the number of
      infectious individuals. Finally, we show that ecological interactions among host
      species have a weaker influence on pathogen circulation than inter-species
      transmission rates. We conclude that integration of a community perspective to
      study wildlife pathogens is crucial, especially in the context of understanding
      and predicting infectious disease emergence events.

PMID- 22966137
TI  - Biodiversity loss decreases parasite diversity: theory and patterns.
AB  - Past models have suggested host-parasite coextinction could lead to linear, or
      concave down relationships between free-living species richness and parasite
      richness. I explored several models for the relationship between parasite
      richness and biodiversity loss. Life cycle complexity, low generality of
      parasites and sensitivity of hosts reduced the robustness of parasite species to
      the loss of free-living species diversity. Food-web complexity and the ordering
      of extinctions altered these relationships in unpredictable ways. Each
      disassembly of a food web resulted in a unique relationship between parasite
      richness and the richness of free-living species, because the extinction
      trajectory of parasites was sensitive to the order of extinctions of free-living
      species. However, the average of many disassemblies tended to approximate an
      analytical model. Parasites of specialist hosts and hosts higher on food chains
      were more likely to go extinct in food-web models. Furthermore, correlated
      extinctions between hosts and parasites (e.g. if parasites share a host with a
      specialist predator) led to steeper declines in parasite richness with
      biodiversity loss. In empirical food webs with random removals of free-living
      species, the relationship between free-living species richness and parasite
      richness was, on average, quasi-linear, suggesting biodiversity loss reduces
      parasite diversity more than previously thought.

PMID- 22966138
TI  - Disease and the dynamics of extinction.
AB  - Invading infectious diseases can, in theory, lead to the extinction of host
      populations, particularly if reservoir species are present or if disease
      transmission is frequency-dependent. The number of historic or prehistoric
      extinctions that can unequivocally be attributed to infectious disease is
      relatively small, but gathering firm evidence in retrospect is extremely
      difficult. Amphibian chytridiomycosis and Tasmanian devil facial tumour disease
      (DFTD) are two very different infectious diseases that are currently threatening
      to cause extinctions in Australia. These provide an unusual opportunity to
      investigate the processes of disease-induced extinction and possible management
      strategies. Both diseases are apparently recent in origin. Tasmanian DFTD is
      entirely host-specific but potentially able to cause extinction because
      transmission depends weakly, if at all, on host density. Amphibian
      chytridiomycosis has a broad host range but is highly pathogenic only to some
      populations of some species. At present, both diseases can only be managed by
      attempting to isolate individuals or populations from disease. Management options
      to accelerate the process of evolution of host resistance or tolerance are being
      investigated in both cases. Anthropogenic changes including movement of diseases
      and hosts, habitat destruction and fragmentation and climate change are likely to
      increase emerging disease threats to biodiversity and it is critical to further
      develop strategies to manage these threats.

PMID- 22966139
TI  - Parasite invasion following host reintroduction: a case study of Yellowstone's
      wolves.
AB  - Wildlife reintroductions select or treat individuals for good health with the
      expectation that these individuals will fare better than infected animals.
      However, these individuals, new to their environment, may also be particularly
      susceptible to circulating infections and this may result in high morbidity and
      mortality, potentially jeopardizing the goals of recovery. Here, using the
      reintroduction of the grey wolf (Canis lupus) into Yellowstone National Park as a
      case study, we address the question of how parasites invade a reintroduced
      population and consider the impact of these invasions on population performance.
      We find that several viral parasites rapidly invaded the population inside the
      park, likely via spillover from resident canid species, and we contrast these
      with the slower invasion of sarcoptic mange, caused by the mite Sarcoptes
      scabiei. The spatio-temporal patterns of mange invasion were largely consistent
      with patterns of host connectivity and density, and we demonstrate that the area
      of highest resource quality, supporting the greatest density of wolves, is also
      the region that appears most susceptible to repeated disease invasion and
      parasite-induced declines. The success of wolf reintroduction appears not to have
      been jeopardized by infectious disease, but now shows signs of regulation or
      limitation modulated by parasites.

PMID- 22966140
TI  - The emergence and spread of finch trichomonosis in the British Isles.
AB  - Finch trichomonosis, caused by the protozoal parasite Trichomonas gallinae, was
      first recognized as an emerging infectious disease of British passerines in 2005.
      The first year of seasonal epidemic mortality occurred in 2006 with significant
      declines of greenfinch Carduelis chloris and chaffinch Fringilla coelebs
      populations. Here, we demonstrate that large-scale mortality, principally of
      greenfinch, continued in subsequent years, 2007-2009, with a shifting
      geographical distribution across the British Isles over time. Consequent to the
      emergence of finch trichomonosis, the breeding greenfinch population in Great
      Britain has declined from ca 4.3 million to ca 2.8 million birds and the maximum
      mean number of greenfinches (a proxy for flock size) visiting gardens has
      declined by 50 per cent. The annual rate of decline of the breeding greenfinch
      population within England has exceeded 7 per cent since the initial epidemic.
      Although initially chaffinch populations were regionally diminished by the
      disease, this has not continued. Retrospective analyses of disease surveillance
      data showed a rapid, widespread emergence of finch trichomonosis across Great
      Britain in 2005 and we hypothesize that the disease emerged by T. gallinae
      jumping from columbiforms to passeriforms. Further investigation is required to
      determine the continuing impact of finch trichomonosis and to develop our
      understanding of how protozoal diseases jump host species.

PMID- 22966141
TI  - Human viruses: discovery and emergence.
AB  - There are 219 virus species that are known to be able to infect humans. The first
      of these to be discovered was yellow fever virus in 1901, and three to four new
      species are still being found every year. Extrapolation of the discovery curve
      suggests that there is still a substantial pool of undiscovered human virus
      species, although an apparent slow-down in the rate of discovery of species from
      different families may indicate bounds to the potential range of diversity. More
      than two-thirds of human viruses can also infect non-human hosts, mainly mammals,
      and sometimes birds. Many specialist human viruses also have mammalian or avian
      origins. Indeed, a substantial proportion of mammalian viruses may be capable of
      crossing the species barrier into humans, although only around half of these are
      capable of being transmitted by humans and around half again of transmitting well
      enough to cause major outbreaks. A few possible predictors of species jumps can
      be identified, including the use of phylogenetically conserved cell receptors. It
      seems almost inevitable that new human viruses will continue to emerge, mainly
      from other mammals and birds, for the foreseeable future. For this reason, an
      effective global surveillance system for novel viruses is needed.

PMID- 22966142
TI  - Bringing together emerging and endemic zoonoses surveillance: shared challenges
      and a common solution.
AB  - Early detection of disease outbreaks in human and animal populations is crucial
      to the effective surveillance of emerging infectious diseases. However, there are
      marked geographical disparities in capacity for early detection of outbreaks,
      which limit the effectiveness of global surveillance strategies. Linking
      surveillance approaches for emerging and neglected endemic zoonoses, with a
      renewed focus on existing disease problems in developing countries, has the
      potential to overcome several limitations and to achieve additional health
      benefits. Poor reporting is a major constraint to the surveillance of both
      emerging and endemic zoonoses, and several important barriers to reporting can be
      identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of
      capacity to enforce regulations; (iii) poor communication among communities,
      institutions and sectors; and (iv) complexities of the international regulatory
      environment. Redirecting surveillance efforts to focus on endemic zoonoses in
      developing countries offers a pragmatic approach that overcomes some of these
      barriers and provides support in regions where surveillance capacity is currently
      weakest. In addition, this approach addresses immediate health and development
      problems, and provides an equitable and sustainable mechanism for building the
      culture of surveillance and the core capacities that are needed for all zoonotic
      pathogens, including emerging disease threats.

PMID- 22966144
TI  - National and international policies to mitigate disease threats.
AB  - To devise and implement effective health policy, we must define the problem,
      choose the tools, craft the policy, build consensus, set goals and deadlines,
      raise funds and take action. Success or failure depends on the perception of
      risk, the strength of the underlying science, the efficacy of the technology,
      ownership and intellectual property, the conflict between individual and public
      health, the choice of weaker (guidelines) and stronger (law) policy instruments,
      the level of public interest, political opportunity, institutional inertia,
      mechanisms for enforcement and who foots the bill. All these things considered,
      this paper is a brief policy-making guide by example, illustrating some
      achievements and disappointments with reference to cholera, drug-resistant
      tuberculosis, HIV/AIDS and rabies.

PMID- 22966143
TI  - A framework for the study of zoonotic disease emergence and its drivers:
      spillover of bat pathogens as a case study.
AB  - Many serious emerging zoonotic infections have recently arisen from bats,
      including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies
      and rabies-related viruses, consistent with the overall observation that wildlife
      are an important source of emerging zoonoses for the human population. Mechanisms
      underlying the recognized association between ecosystem health and human health
      remain poorly understood and responding appropriately to the ecological, social
      and economic conditions that facilitate disease emergence and transmission
      represents a substantial societal challenge. In the context of disease emergence
      from wildlife, wildlife and habitat should be conserved, which in turn will
      preserve vital ecosystem structure and function, which has broader implications
      for human wellbeing and environmental sustainability, while simultaneously
      minimizing the spillover of pathogens from wild animals into human beings. In
      this review, we propose a novel framework for the holistic and interdisciplinary
      investigation of zoonotic disease emergence and its drivers, using the spillover
      of bat pathogens as a case study. This study has been developed to gain a
      detailed interdisciplinary understanding, and it combines cutting-edge
      perspectives from both natural and social sciences, linked to policy impacts on
      public health, land use and conservation.

PMID- 22966146
TI  - Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist
      AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active
      disease despite treatment with methotrexate or sulphasalazine.
AB  - OBJECTIVES: The P2X(7) purinergic receptor antagonist AZD9056 was evaluated in a
      phase IIa study and subsequently in a phase IIb study to assess the effects of
      orally administered AZD9056 on the signs/symptoms of rheumatoid arthritis (RA),
      with American College of Rheumatology 20% response criteria (ACR20) as the
      primary outcome. METHODS: Both studies were randomised, double-blind, placebo
      controlled, parallel-group studies in patients with RA receiving methotrexate or
      sulphasalazine. Phase IIa was an ascending-dose trial in two cohorts (n=75) using
      AZD9056 administered daily over 4 weeks. Phase IIb included an open-label
      etanercept treatment group. Patients were randomised to receive treatment for 6
      months with 50, 100, 200 or 400 mg AZD9056 (oral, once a day) or matching placebo
      (oral, once a day), or subcutaneous etanercept (50 mg once a week). RESULTS: In
      phase IIa, 65% of AZD9056 recipients at 400 mg/day responded at the ACR20 level
      compared with 27% of placebo-treated patients. A significant reduction in swollen
      and tender joint count was observed in the actively treated group compared with
      placebo, whereas no effect on acute-phase response was observed. Of 385
      randomised patients in the phase IIb study, 383 received treatment. AZD9056 (all
      doses) had no clinically or statistically significant effect on RA relative to
      placebo as measured by the proportion of patients meeting the ACR20 criteria at 6
      months and further supported by secondary end points. In both studies AZD9056 was
      well tolerated up to 400 mg/day. CONCLUSIONS: AZD9056 does not have significant
      efficacy in the treatment of RA, and the P2X(7) receptor does not appear to be a
      therapeutically useful target in RA. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT00520572.

PMID- 22966147
TI  - Paliperidone palmitate for schizophrenia.

PMID- 22966145
TI  - Elevated extracellular glucose and uncontrolled type 1 diabetes enhance NFAT5
      signaling and disrupt the transverse tubular network in mouse skeletal muscle.
AB  - The transcription factor nuclear factor of activated T-cells 5 (NFAT5) is a key
      protector from hypertonic stress in the kidney, but its role in skeletal muscle
      is unexamined. Here, we evaluate the effects of glucose hypertonicity and
      hyperglycemia on endogenous NFAT5 activity, transverse tubular system morphology
      and Ca(2+) signaling in adult murine skeletal muscle fibers. We found that
      exposure to elevated glucose (25-50 mmol/L) increased NFAT5 expression and
      nuclear translocation, and NFAT-driven transcriptional activity. These effects
      were insensitive to the inhibition of calcineurin A, but sensitive to both
      p38alpha mitogen-activated protein kinases and phosphoinositide 3-kinase-related
      kinase inhibition. Fibers exposed to elevated glucose exhibited disrupted
      transverse tubular morphology, characterized by swollen transverse tubules and an
      increase in longitudinal connections between adjacent transverse tubules. Ca(2+)
      transients elicited by a single, brief electric field stimuli were increased in
      amplitude in fibers challenged by elevated glucose. Muscle fibers from type 1
      diabetic mice exhibited increased NFAT5 expression and transverse tubule
      disruptions, but no differences in electrically evoked Ca(2+) transients. Our
      results suggest the hypothesis that these changes in skeletal muscle could play a
      role in the pathophysiology of acute and severe hyperglycemic episodes commonly
      observed in uncontrolled diabetes.

PMID- 22966148
TI  - Decreased birth weight in psychosis: influence of prenatal exposure to
      serologically determined influenza and hypoxia.
AB  - BACKGROUND: Decreased birth weight (BW) is associated with later psychosis, but
      the sources of decreased BW for those at risk for psychosis remain unclear. AIM:
      To determine whether fetal exposure to influenza and/or hypoxia accounts for BW
      decreases among psychotic cases and controls. METHOD: Subjects were 111 cases
      diagnosed with schizophrenia or affective psychosis and 333 matched controls from
      the Collaborative Perinatal Project. Psychiatric diagnoses were ascertained from
      medical records. Influenza and hypoxia were determined from maternal and cord
      sera collected at birth. RESULTS: Cases exposed to severe fetal hypoxia or
      influenza had significantly lower BW compared with unexposed cases and controls,
      regardless of exposure status. No significant differences in BW were observed
      among controls based on exposure status. CONCLUSIONS: Decreased BW appears to be
      a risk factor for psychosis only in the presence of other teratogens. Liability
      to psychosis likely renders fetuses vulnerable to decreased fetal growth in
      response to hypoxia and influenza.

PMID- 22966149
TI  - Exercise reveals the interrelation of physical fitness, inflammatory response,
      psychopathology, and autonomic function in patients with schizophrenia.
AB  - Maintaining and improving fitness are associated with a lower risk of premature
      death from cardiovascular disease. Patients with schizophrenia are known to
      exercise less and have poorer health behaviors than average. Physical fitness and
      physiological regulation during exercise tasks have not been investigated to date
      among patients with schizophrenia. We studied autonomic modulation in a stepwise
      exhaustion protocol in 23 patients with schizophrenia and in matched controls,
      using spirometry and lactate diagnostics. Parameters of physical capacity were
      determined at the aerobic, anaerobic, and vagal thresholds (VT), as well as for
      peak output. VT was correlated with psychopathology, as assessed by the Positive
      and Negative Syndrome Scale, with the inflammatory markers IL-1beta, IL-6, and
      TNF-alpha and with peak output. The MANOVA for heart and breathing rates, as well
      as for vagal modulation and complexity behavior of heart rate, indicated a
      profound lack of vagal modulation at all intensity levels, even after the
      covariate carbon monoxide concentration was introduced as a measure of smoking
      behavior. Significantly decreased physical capacity was demonstrated at the
      aerobic, anaerobic, and VT in patients. After the exercise task, reduced vagal
      modulation in patients correlated negatively with positive symptoms and with
      levels of IL-6 and TNF-alpha. This study shows decreased physical capacity in
      patients with schizophrenia. Upcoming intervention studies need to take into
      account the autonomic imbalance, which might predispose patients to arrhythmias
      during exercise. Results of inflammatory parameters are suggestive of a reduced
      activity of the anti-inflammatory cholinergic pathway in patients, leading to a
      pro-inflammatory state. 

PMID- 22966150
TI  - Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious
      exposure.
AB  - BACKGROUND: Genome-wide association studies (GWAS) implicate single nucleotide
      polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA)
      region, as common risk factors for schizophrenia (SZ). Other studies implicate
      viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on
      SZ risk with and without exposure. METHOD: GWAS-significant SNPs and ancestry
      informative marker SNPs were analyzed among African American patients with SZ (n
      = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1),
      cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific
      antibody assays. RESULTS: Five SNPs were nominally associated with SZ, adjusted
      for population admixture (P < .05, uncorrected for multiple comparisons). These
      SNPs were next analyzed in relation to infectious exposure. Multivariate analysis
      indicated significant association between rs3130297 genotype and HSV-1 exposure;
      the associated allele was different from the SZ risk allele. CONCLUSIONS: We
      propose a model for the genesis of SZ incorporating genomic variation in the HLA
      region and neurotropic viral exposure for testing in additional, independent
      African American samples.

PMID- 22966152
TI  - A twist on the athlete's ankle twist: some ankles are more equal than others.

PMID- 22966153
TI  - Two simple clinical tests for predicting onset of medial tibial stress syndrome:
      shin palpation test and shin oedema test.
AB  - OBJECTIVE: To examine the relationship between two clinical test results and
      future diagnosis of (Medial Tibial Stress Syndrome) MTSS in personnel at a
      military trainee establishment. DESIGN: Data from a preparticipation
      musculoskeletal screening test performed on 384 Australian Defence Force Academy
      Officer Cadets were compared against 693 injuries reported by 326 of the Officer
      Cadets in the following 16 months. Data were held in an Injury Surveillance
      database and analysed using chi2 and Fisher's Exact tests, and Receiver Operating
      Characteristic Curve analysis. MAIN OUTCOME MEASURE: Diagnosis of MTSS, confirmed
      by an independent blinded health practitioner. RESULTS: Both the palpation and
      oedema clinical tests were each found to be significant predictors for later
      onset of MTSS. Specifically: Shin palpation test OR 4.63, 95% CI 2.5 to 8.5,
      Positive Likelihood Ratio 3.38, Negative Likelihood Ratio 0.732, Pearson chi2
      p<0.001; Shin oedema test OR 76.1 95% CI 9.6 to 602.7, Positive Likelihood Ratio
      7.26, Negative Likelihood Ratio 0.095, Fisher's Exact p<0.001; Combined Shin
      Palpation Test and Shin Oedema Test Positive Likelihood Ratio 7.94, Negative
      Likelihood Ratio <0.001, Fisher's Exact p<0.001. Female gender was found to be an
      independent risk factor (OR 2.97, 95% CI 1.66 to 5.31, Positive Likelihood Ratio
      2.09, Negative Likelihood Ratio 0.703, Pearson chi2 p<0.001) for developing MTSS.
      CONCLUSION: The tests for MTSS employed here are components of a normal clinical
      examination used to diagnose MTSS. This paper confirms that these tests and
      female gender can also be confidently applied in predicting those in an
      asymptomatic population who are at greater risk of developing MTSS symptoms with
      activity at some point in the future.

PMID- 22966151
TI  - Current opportunities and challenges in microbial metagenome analysis--a
      bioinformatic perspective.
AB  - Metagenomics has become an indispensable tool for studying the diversity and
      metabolic potential of environmental microbes, whose bulk is as yet non
      cultivable. Continual progress in next-generation sequencing allows for
      generating increasingly large metagenomes and studying multiple metagenomes over
      time or space. Recently, a new type of holistic ecosystem study has emerged that
      seeks to combine metagenomics with biodiversity, meta-expression and contextual
      data. Such 'ecosystems biology' approaches bear the potential to not only advance
      our understanding of environmental microbes to a new level but also impose
      challenges due to increasing data complexities, in particular with respect to
      bioinformatic post-processing. This mini review aims to address selected
      opportunities and challenges of modern metagenomics from a bioinformatics
      perspective and hopefully will serve as a useful resource for microbial
      ecologists and bioinformaticians alike.

PMID- 22966155
TI  - Partial opening and subconductance gating of mechanosensitive ion channels in
      dystrophic skeletal muscle.
AB  - We recorded the activity of single mechanosensitive (MS) ion channels in skeletal
      muscle from the mdx mouse, a deletion mutant that lacks the cytoskeletal protein,
      dystrophin. Experiments were designed to examine the influence of dystrophin, a
      major component of skeletal muscle costameres, on the behaviour of single MS
      channels. In the majority of recordings from cell-attached patches, MS channels
      have a conductance of ~23 pS. Recordings from some patches, however, showed a
      smaller conductance channel of ~7-14 pS. Large and small conductance channels
      were detected in a single patch and showed serial, non-random gating, suggesting
      different opening levels of a single channel. Analysis of the distribution of
      current amplitudes within the open channel showed MS channels fluctuate between
      subconductance levels. MS channels in dystrophic muscle spend ~60% of the time at
      smaller subconductance levels, often failing to reach the fully open level.
      Applying pressure to the membrane of mdx fibres increases in a graded manner
      occupancy of the fully open state, while reducing occupancy of subconductance
      levels. Recordings also show partial openings of MS channels in both wild-type
      and mdx muscle that fail to reach the fully open state. Partial openings occur at
      a higher frequency in mdx muscle and reflect occupancy of subconductance levels
      seen during complete activations. In muscle from mdx/utrn(-/-) double knockout
      mice, MS channels also spend more time at subconductance levels than the fully
      open state. Conductance variability of MS channels may represent gating of a
      heteromeric protein composed of different channel subunits. The results also show
      that partial opening and prolonged burst duration are distinct mechanisms that
      contribute to excess Ca(2+) entry in dystrophic muscle.

PMID- 22966157
TI  - The effects of slow skeletal troponin I expression in the murine myocardium are
      influenced by development-related shifts in myosin heavy chain isoform.
AB  - Troponin I (TnI) and myosin heavy chain (MHC) are two contractile regulatory
      proteins that undergo major shifts in isoform expression as cardiac myocytes
      mature from embryonic to adult stages. To date, many studies have investigated
      individual effects of embryonic vs. cardiac isoforms of either TnI or MHC on
      cardiac muscle function and contractile dynamics. Thus, we sought to determine
      whether concomitant expression of the embryonic isoforms of both TnI and MHC had
      functional effects that were not previously observed. Adult transgenic (TG) mice
      that express the embryonic isoform of TnI, slow skeletal TnI (ssTnI), were
      treated with propylthiouracil (PTU) to revert MHC expression from adult (alpha
      MHC) to embryonic (beta-MHC) isoforms. Cardiac muscle fibres from these mice
      contained ~80% beta-MHC and ~34% ssTnI of total MHC or TnI, respectively,
      allowing us to test the functional effects of ssTnI in the presence of beta-MHC.
      Detergent-skinned cardiac muscle fibre bundles were used to study how the
      interplay between MHC and TnI modulate muscle length-mediated effect on
      crossbridge (XB) recruitment dynamics, Ca(2+)-activated tension, and ATPase
      activity. One major finding was that the model-predicted XB recruitment rate (b)
      was enhanced significantly by ssTnI, and this speeding effect of ssTnI on XB
      recruitment rate was much greater (3.8-fold) when beta-MHC was present. Another
      major finding was that the previously documented ssTnI-mediated increase in
      myofilament Ca(2+) sensitivity (pCa(50)) was blunted when beta-MHC was present.
      ssTnI expression increased pCa(50) by 0.33 in alpha-MHC fibres, whereas ssTnI
      increased pCa(50) by only 0.05 in beta-MHC fibres. Our study provides new
      evidence for significant interplay between MHC and TnI isoforms that is essential
      for tuning cardiac contractile function. Thus, MHC-TnI interplay may provide a
      developmentally dependent mechanism to enhance XB recruitment dynamics at a time
      when Ca(2+)-handling mechanisms are underdeveloped, and to prevent excessive
      ssTnI-dependent inotropy (increased Ca(2+) sensitivity) in the embryonic
      myocardium.

PMID- 22966159
TI  - Characterization of a novel phosphorylation site in the sodium-chloride
      cotransporter, NCC.
AB  - The sodium-chloride cotransporter, NCC, is essential for renal electrolyte
      balance. NCC function can be modulated by protein phosphorylation. In this study,
      we characterized the role and physiological regulation of a novel phosphorylation
      site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124
      NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which
      was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy
      with kidney tubule segment-specific markers localized pS124-NCC to all distal
      convoluted tubule cells. Double immunogold electron microscopy demonstrated that
      pS124-NCC co-localized with total NCC in the apical plasma membrane of distal
      convoluted tubule cells and intracellular vesicles. Acute treatment of Munich
      Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2
      receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with
      no changes in total NCC plasma membrane abundance. pS124-NCC levels also
      increased in abundance in rats after stimulation of the renin-angiotensin
      aldosterone system by dietary low sodium intake. In contrast to other NCC
      phosphorylation sites, the STE20/SPS1-related proline-alanine-rich kinase and
      oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate
      NCC at S124. Protein kinase arrays identified multiple kinases that were able to
      bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin
      D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at
      S124. In oocytes, (36)Cl uptake studies combined with biochemical analysis showed
      decreased activity of plasma membrane-associated NCC when replacing S124 with
      alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell
      lines, S124A and S124D mutants were able to traffic to the plasma membrane
      similarly to wildtype NCC.

PMID- 22966158
TI  - Adult-like action potential properties and abundant GABAergic synaptic responses
      in amygdala neurons from newborn marmosets.
AB  - The amygdala plays an important role in the processing of emotional events. This
      information processing is altered by development, but little is known about the
      development of electrophysiological properties of neurons in the amygdala. We
      studied the postnatal development of electrophysiological properties of neurons
      in the basolateral amygdala (BLA) of the common marmoset (Callithrix jacchus).
      Whole-cell patch-clamp recordings were obtained from BLA pyramidal neurons in
      brain slices prepared from developing and adult marmosets, and
      electrophysiological properties known to change during development in rats were
      analysed. Two passive electrical properties of the neuronal membrane - the input
      resistance (R(in)) and the membrane time constant () - significantly decreased
      with postnatal development. In contrast, the action potential only showed a
      slight decrease in duration during the first month of life, whereas the amplitude
      did not change after birth. Passive electrical properties and action potentials
      in neurons of 4-week-old marmosets were similar to those in neurons of 4-year-old
      marmosets. The development of the action potential duration was not correlated
      with the development of R(in) or , whereas the development of R(in) and was
      correlated with each other. Abundant spontaneous and noradrenaline-induced
      GABAergic currents were present immediately after birth and did not change during
      postnatal development. These results suggest that newborn infant marmoset BLA
      pyramidal neurons possess relatively mature action potentials and receive
      vigorous GABAergic synaptic inputs, and that they acquire adult-like
      electrophysiological properties by the fourth week of life.

PMID- 22966160
TI  - PIP2 hydrolysis stimulates the electrogenic Na+-bicarbonate cotransporter NBCe1-B
      and -C variants expressed in Xenopus laevis oocytes.
AB  - Electrogenic Na(+)-bicarbonate cotransporter NBCe1 variants contribute to pH(i)
      regulation, and promote ion reabsorption or secretion by many epithelia. Most
      Na(+)-coupled bicarbonate transporter (NCBT) families such as NBCe1 contain
      variants with differences primarily at the cytosolic N and/or C termini that are
      likely to impart on the transporters different modes of regulation. For example,
      N-terminal regions of NBCe1 autoregulate activity. Our group previously reported
      that cytosolic phosphatidylinositol 4,5-bisphosphate (PIP(2)) stimulates
      heterologously expressed rat NBCe1-A in inside-out macropatches excised from
      Xenopus laevis oocytes. In the current study on whole oocytes, we used the two
      electrode voltage-clamp technique, as well as pH- and voltage-sensitive
      microelectrodes, to characterize the effect of injecting PIP(2) on the activity
      of heterologously expressed NBCe1-A, -B, or -C. Injecting PIP(2) (10 MUM
      estimated final) into voltage-clamped oocytes stimulated NBC-mediated, HCO(3)(-)
      induced outward currents by >100% for the B and C variants, but not for the A
      variant. The majority of this stimulation involved PIP(2) hydrolysis and
      endoplasmic reticulum (ER) Ca(2+) release. Stimulation by PIP(2) injection was
      mimicked by injecting IP(3), but inhibited by either applying the phospholipase C
      (PLC) inhibitor U73112 or depleting ER Ca(2+) with prolonged thapsigargin/EGTA
      treatment. Stimulating the activity of store-operated Ca(2+) channels (SOCCs) to
      trigger a Ca(2+) influx mimicked the PIP(2)/IP(3) stimulation of the B and C
      variants. Activating the endogenous G(q) protein-coupled receptor in oocytes with
      lysophosphatidic acid (LPA) also stimulated the B and C variants in a Ca(2+)
      dependent manner, although via an increase in surface expression for the B
      variant. In simultaneous voltage-clamp and pH(i) studies on NBCe1-C-expressing
      oocytes, LPA increased the NBC-mediated pH(i)-recovery rate from a CO(2)-induced
      acid load by ~80%. Finally, the general kinase inhibitor staurosporine completely
      inhibited the IP(3)-induced stimulation of NBCe1-C. In summary, injecting PIP(2)
      stimulates the activity of NBCe1-B and -C expressed in oocytes through an
      increase in IP(3)/Ca(2+) that involves a staurosporine-sensitive kinase. In
      conjunction with our previous macropatch findings, PIP(2) regulates NBCe1 through
      a dual pathway involving both a direct stimulatory effect of PIP(2) on at least
      NBCe1-A, as well as an indirect stimulatory effect of IP(3)/Ca(2+) on the B and C
      variants.

PMID- 22966161
TI  - Reduced corticomotor excitability and motor skills development in children born
      preterm.
AB  - The mechanisms underlying the altered neurodevelopment commonly experienced by
      children born preterm, but without brain lesions, remain unknown. While
      individuals born the earliest are at most risk, late preterm children also
      experience significant motor, cognitive and behavioural dysfunction from school
      age, and reduced income and educational attainment in adulthood. We used
      transcranial magnetic stimulation and functional assessments to examine
      corticomotor development in 151 children without cerebral palsy, aged 10-13 years
      and born after gestations of 25-41 completed weeks. We hypothesized that motor
      cortex and corticospinal development are altered in preterm children, which
      underpins at least some of their motor dysfunction. We report for the first time
      that every week of reduced gestation is associated with a reduction in
      corticomotor excitability that remains evident in late childhood. This reduced
      excitability was associated with poorer motor skill development, particularly
      manual dexterity. However, child adiposity, sex and socio-economic factors
      regarding the child's home environment soon after birth were also powerful
      influences on development of motor skills. Preterm birth was also associated with
      reduced left hemisphere lateralization, but without increasing the likelihood of
      being left handed per se. These corticomotor findings have implications for
      normal motor development, but also raise questions regarding possible longer term
      consequences of preterm birth on motor function.

PMID- 22966162
TI  - High blood pressure associates with the remodelling of inward rectifier K+
      channels in mice mesenteric vascular smooth muscle cells.
AB  - The increased vascular tone that defines essential hypertension is associated
      with depolarization of vascular smooth muscle cells (VSMCs) and involves a change
      in the expression profile of ion channels promoting arterial contraction. As a
      major regulator of VSMC resting membrane potential (V(M)), K(+) channel activity
      is an important determinant of vascular tone and vessel diameter. However,
      hypertension-associated changes in the expression and/or modulation of K(+)
      channels are poorly defined, due to their large molecular diversity and their bed
      specific pattern of expression. Moreover, the impact of these changes on the
      integrated vessel function and their contribution to the development of altered
      vascular tone under physiological conditions need to be confirmed. Hypertensive
      (BPH) and normotensive (BPN) mice strains obtained by phenotypic selection were
      used to explore whether changes in the functional expression of VSMC inward
      rectifier K(+) channels contribute to the more depolarized resting V(M) and the
      increased vascular reactivity of hypertensive arteries. We determined the
      expression levels of inward rectifier K(+) channel mRNA in several vascular beds
      from BPN and BPH animals, and their functional contribution to VSMC excitability
      and vascular tone in mesenteric arteries. We found a decrease in the expression
      of Kir2.1, Kir4.1, Kir6.x and SUR2 mRNA in BPH VSMCs, and a decreased functional
      contribution of both K(IR) and K(ATP) channels in isolated BPH VSMCs. However,
      only the effect of K(ATP) channel modulators was impaired when exploring vascular
      tone, suggesting that decreased functional expression of K(ATP) channels may be
      an important element in the remodelling of VSMCs in essential hypertension.

PMID- 22966163
TI  - Acute vagal stimulation attenuates cardiac metabolic response to beta-adrenergic
      stress.
AB  - The effects of vagal stimulation (VS) on cardiac energy substrate metabolism are
      unknown. We tested the hypothesis that acute VS alters the balance between free
      fatty acid (FFA) and carbohydrate oxidation and opposes the metabolic effects of
      beta-adrenergic stimulation. A clinical-type selective stimulator of the vagal
      efferent fibres was connected to the intact right vagus in chronically
      instrumented dogs. VS was set to reduce heart rate by 30 beats min(-1), and the
      confounding effects of bradycardia were then eliminated by pacing the heart at
      165 beats min(-1). [(3)H]Oleate and [(14)C]glucose were infused to measure FFA
      and glucose oxidation. The heart was subjected to beta-adrenergic stress by
      infusing dobutamine at 5, 10 and 15 MUg kg(-1) min(-1) before and during VS. VS
      did not significantly affect baseline cardiac performance, haemodynamics or
      myocardial metabolism. However, at peak dobutamine stress, VS attenuated the
      increase in left ventricular pressure-diameter area from 235.9 +/- 72.8 to 167.3
      +/- 55.8%, and in cardiac oxygen consumption from 173.9 +/- 23.3 to 127.89 +/-
      6.2% (both P < 0.05), and thus mechanical efficiency was not enhanced. The
      increase in glucose oxidation fell from 289.3 +/- 55.5 to 131.1 +/- 20.9% (P <
      0.05), while FFA oxidation was not increased by beta-adrenergic stress and fell
      below baseline during VS only at the lowest dose of dobutamine. The functional
      and in part the metabolic changes were reversed by 0.1 mg kg(-1) atropine i.v.
      Our data show that acute right VS does not affect baseline cardiac metabolism,
      but attenuates myocardial oxygen consumption and glucose oxidation in response to
      adrenergic stress, thus functioning as a cardio-selective antagonist to beta
      adrenergic activation.

PMID- 22966165
TI  - Human plasmacytoid dendritic cells are equipped with antigen-presenting and
      tumoricidal capacities.
AB  - Human plasmacytoid dendritic cells (pDCs) represent a highly specialized
      naturally occurring dendritic-cell subset and are the main producers of type I
      interferons (IFNs) in response to viral infections. We show that human pDCs
      activated by the preventive vaccine FSME specifically up-regulate CD56 on their
      surface, a marker that was thought to be specific for NK cells and associated
      with cytolytic effector functions. We observed that FSME-activated pDCs
      specifically lysed NK target cells and expressed cytotoxic molecules, such as
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and granzyme B.
      Elevated levels of these molecules coincided with the expression of CD56,
      indicative for skewing human pDCs toward an interferon-producing killer DC
      subset. Detailed phenotypical and functional analysis revealed that pDCs attained
      a mature phenotype, secreted proinflammatory cytokines, and had the capacity to
      present antigens and stimulate T cells. Here, we report on the generation of
      CD56(+) human interferon producing killer pDCs with the capacity to present
      antigens. These findings aid in deciphering the role for pDCs in antitumor
      immunity and present a promising prospect of developing antitumor therapy using
      pDCs.

PMID- 22966164
TI  - Lifelong physical activity preserves functional sympatholysis and purinergic
      signalling in the ageing human leg.
AB  - Ageing is associated with an impaired ability to modulate sympathetic
      vasoconstrictor activity (functional sympatholysis) and a reduced exercise
      hyperaemia. The purpose of this study was to investigate whether a physically
      active lifestyle can offset the impaired functional sympatholysis and exercise
      hyperaemia in the leg and whether ATP signalling is altered by ageing and
      physical activity. Leg haemodynamics, interstitial [ATP] and P2Y(2) receptor
      content was determined in eight young (23 +/- 1 years), eight lifelong sedentary
      elderly (66 +/- 2 years) and eight lifelong active elderly (62 +/- 2 years) men
      at rest and during one-legged knee extensions (12 W and 45% maximal workload
      (WL(max))) and arterial infusion of ACh and ATP with and without tyramine. The
      vasodilatory response to ACh was lowest in the sedentary elderly, higher in
      active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP
      induced vasodilatation was lower in the sedentary elderly (P < 0.05). During
      exercise (12 W), leg blood flow, vascular conductance and VO2 was lower and leg
      lactate release higher in the sedentary elderly compared to the young (P < 0.05),
      whereas there was no difference between the active elderly and young.
      Interstitial [ATP] during exercise and P2Y(2) receptor content were higher in the
      active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion
      lowered resting vascular conductance in all groups, but only in the sedentary
      elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator
      response to ATP infusion in any of the three groups. Plasma [noradrenaline]
      increased more during tyramine infusion in both elderly groups compared to young
      (P < 0.05). A lifelong physically active lifestyle can maintain an intact
      functional sympatholysis during exercise and vasodilator response to ATP despite
      a reduction in endothelial nitric oxide function. A physically active lifestyle
      increases interstitial ATP levels and skeletal muscle P2Y(2) receptor content.

PMID- 22966166
TI  - Super-resolution imaging of remodeled synaptic actin reveals different synergies
      between NK cell receptors and integrins.
AB  - Natural killer (NK) cells secrete lytic granules to directly kill virus-infected
      or transformed cells and secrete cytokines to communicate with other cells. Three
      dimensional super-resolved images of F-actin, lytic granules, and IFN-gamma in
      primary human NK cells stimulated through different activating receptors reveal
      that both IFN-gamma and lytic granules accumulated in domains where the
      periodicity of the cortical actin mesh at the synapse opened up to be penetrable.
      Ligation of some activating receptors alone (eg, CD16 or NKG2D) was sufficient to
      increase the periodicity of the actin mesh, but surprisingly, ligation of others
      (eg, NKp46 or CD2) was not sufficient to induce cortical actin remodeling unless
      LFA-1 was coligated. Importantly, influenza virus particles that can be
      recognized by NK cells similarly did not open the actin mesh but could if LFA-1
      was coligated. This leads us to propose that immune cells using germline-encoded
      receptors to directly recognize foreign proteins can use integrin recognition to
      differentiate between free pathogens and pathogen-infected cells that will both
      be present in blood. This distinction would not be required for NK cell
      receptors, such as NKG2D, which recognize host cell-encoded proteins that can
      only be found on diseased cells and not pathogens.

PMID- 22966167
TI  - Mesenchymal stem cells are injured by complement after their contact with serum.
AB  - Despite the potent immunosuppressive activity that mesenchymal stem cells (MSCs)
      display in vitro, recent clinical trial results are disappointing, suggesting
      that MSC viability and/or function are greatly reduced after infusion. In this
      report, we demonstrated that human MSCs activated complement of the innate
      immunity after their contact with serum. Although all 3 known intrinsic cell
      surface complement regulators were present on MSCs, activated complement
      overwhelmed the protection of these regulators and resulted in MSCs cytotoxicity
      and dysfunction. In addition, autologous MSCs suffered less cellular injury than
      allogeneic MSCs after contacting serum. All 3 complement activation pathways were
      involved in generating the membrane attack complex to directly injure MSCs.
      Supplementing an exogenous complement inhibitor, or up-regulating MSC expression
      levels of CD55, one of the cell-surface complement regulators, helped to reduce
      the serum-induced MSC cytotoxicity. Finally, adoptively transferred MSCs in
      complement deficient mice or complement-depleted mice showed reduced cellular
      injury in vivo compared with those in wild type mice. These results indicate that
      complement is integrally involved in recognizing and injuring MSCs after their
      infusion, suggesting that autologous MSCs may have ad-vantages over allogeneic
      MSCs, and that inhibiting complement activation could be a novel strategy to
      improve existing MSC-based therapies.

PMID- 22966168
TI  - VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces
      angiogenesis in transplanted hypoxic tissue.
AB  - Recruitment and retention of leukocytes at a site of blood vessel growth are
      crucial for proper angiogenesis and subsequent tissue perfusion. Although
      critical for many aspects of regenerative medicine, the mechanisms of leukocyte
      recruitment to and actions at sites of angiogenesis are not fully understood. In
      this study, we investigated the signals attracting leukocytes to avascular
      transplanted pancreatic islets and leukocyte actions at the engraftment site.
      Expression of the angiogenic stimulus VEGF-A by mouse pancreatic islets was
      elevated shortly after syngeneic transplantation to muscle. High levels of
      leukocytes, predominantly CD11b(+)/Gr-1(+)/CXCR4(hi) neutrophils, were observed
      at the site of engraftment, whereas VEGF-A-deficient islets recruited only half
      of the amount of leukocytes when transplanted. Acute VEGF-A exposure of muscle
      increased leukocyte extravasation but not the levels of SDF-1alpha. VEGF-A
      recruited neutrophils expressed 10 times higher amounts of MMP-9 than neutrophils
      recruited to an inflammatory stimulus. Revascularization of islets transplanted
      to MMP-9-deficient mice was impaired because blood vessels initially failed to
      penetrate grafts, and after 2 weeks vascularity was still disturbed. This study
      demonstrates that VEGF-A recruits a proangiogenic circulating subset of
      CD11b(+)/Gr-1(+) neutrophils that are CXCR4(hi) and deliver large amounts of the
      effector protein MMP-9, required for islet revascularization and functional
      integration after transplantation.

PMID- 22966169
TI  - t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in
      tumor cell growth.
AB  - Genetic aberrations, including trisomies 3 and 18, and well-defined IGH
      translocations, have been described in marginal zone lymphomas (MZLs); however,
      these known genetic events are present in only a subset of cases. Here, we report
      the cloning of an IGH translocation partner on chromosome X, t(X;14)(p11.4;q32)
      that deregulates expression of an poorly characterized orphan G-protein-coupled
      receptor, GPR34. Elevated GPR34 gene expression was detected independent of the
      translocation in multiple subtypes of non-Hodgkin lymphoma and distinguished a
      unique molecular subtype of MZL. Increased expression of GPR34 was also detected
      in tissue from brain tumors and surface expression of GPR34 was detected on human
      MZL tumor cells and normal immune cells. Overexpression of GPR34 in lymphoma and
      HeLa cells resulted in phosphorylation of ERK, PKC, and CREB; induced CRE, AP1,
      and NF-kappaB-mediated gene transcription; and increased cell proliferation. In
      summary, these results are the first to identify a role for a GPR34 in lymphoma
      cell growth, provide insight into GPR34-mediated signaling, identify a
      genetically unique subset of MZLs that express high levels of GPR34, and suggest
      that MEK inhibitors may be useful for treatment of GPR34-expressing tumors.

PMID- 22966170
TI  - Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence
      of acute chest syndrome among children with sickle cell disease.
AB  - Sickle cell disease is a common hemolytic disorder with a broad range of
      complications, including vaso-occlusive episodes, acute chest syndrome (ACS),
      pain, and stroke. Heme oxygenase-1 (gene HMOX1; protein HO-1) is the inducible,
      rate-limiting enzyme in the catabolism of heme and might attenuate the severity
      of outcomes from vaso-occlusive and hemolytic crises. A (GT)(n) dinucleotide
      repeat located in the promoter region of the HMOX1 gene is highly polymorphic,
      with long repeat lengths linked to decreased activity and inducibility. We
      examined this polymorphism to test the hypothesis that short alleles are
      associated with a decreased risk of adverse outcomes (hospitalization for pain or
      ACS) among a cohort of 942 children with sickle cell disease. Allele lengths
      varied from 13 to 45 repeats and showed a trimodal distribution. Compared with
      children with longer allele lengths, children with 2 shorter alleles (4%; <= 25
      repeats) had lower rates of hospitalization for ACS (incidence rate ratio 0.28,
      95% confidence interval, 0.10-0.81), after adjusting for sex, age, asthma,
      percentage of fetal hemoglobin, and alpha-globin gene deletion. No relationship
      was identified between allele lengths and pain rate. We provide evidence that
      genetic variation in HMOX1 is associated with decreased rates of hospitalization
      for ACS, but not pain. This study is registered at www.clinicaltrials.gov as
      #NCT00072761.

PMID- 22966171
TI  - Platelets increase the proliferation of ovarian cancer cells.
AB  - Platelets promote metastasis and angiogenesis, but their effect on tumor cell
      growth is uncertain. Here we report a direct proliferative effect of platelets on
      cancer cells both in vitro and in vivo. Incubation of platelets with ovarian
      cancer cells from murine (ID8 and 2C6) or human (SKOV3 and OVCAR5) origin
      increased cell proliferation. The proliferative effect of platelets was not
      dependent on direct contact with cancer cells, and preincubation of platelets
      with blocking antibodies against platelet adhesion molecules did not alter their
      effect on cancer cells. The proliferative effect of platelets was reduced by
      fixing platelets with paraformaldehyde, preincubating platelets with a TGF-beta1
      blocking antibody, or reducing expression of TGF-betaR1 receptor on cancer cells
      with siRNA. Infusing platelets into mice with orthotopic ovarian tumors
      significantly increased the proliferation indices in these tumors. Ovarian cancer
      patients with thrombocytosis had higher tumor proliferation indices compared with
      patients with normal platelet counts.

PMID- 22966173
TI  - Reproducibility of image quality for moving objects using respiratory-gated
      computed tomography: a study using a phantom model.
AB  - To investigate the reproducibility of computed tomography (CT) imaging quality in
      respiratory-gated radiation treatment planning is essential in radiotherapy of
      movable tumors. Seven series of regular and six series of irregular respiratory
      motions were performed using a thorax dynamic phantom. For the regular
      respiratory motions, the respiratory cycle was changed from 2.5 to 4 s and the
      amplitude was changed from 4 to 10 mm. For the irregular respiratory motions, a
      cycle of 2.5 to 4 or an amplitude of 4 to 10 mm was added to the base data (i.e.
      3.5-s cycle, 6-mm amplitude) every three cycles. Images of the object were
      acquired six times using respiratory-gated data acquisition. The volume of the
      object was calculated and the reproducibility of the volume was decided based on
      the variety. The registered image of the object was added and the reproducibility
      of the shape was decided based on the degree of overlap of objects. The variety
      in the volumes and shapes differed significantly as the respiratory cycle changed
      according to regular respiratory motions. In irregular respiratory motion, shape
      reproducibility was further inferior, and the percentage of overlap among the six
      images was 35.26% in the 2.5- and 3.5-s cycle mixed group. Amplitude changes did
      not produce significant differences in the variety of the volumes and shapes.
      Respiratory cycle changes reduced the reproducibility of the image quality in
      respiratory-gated CT.

PMID- 22966175
TI  - The UK needs office dermatologists.

PMID- 22966172
TI  - Antigen and substrate withdrawal in the management of autoimmune thrombotic
      disorders.
AB  - Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin
      induced thrombocytopenia, antiphospholipid syndrome and thrombotic
      thrombocytopenic purpura, include immunosuppression and systemic anticoagulation,
      though neither provides optimal outcome for many patients. A different approach
      is suggested by the concurrence of autoantibodies and their antigenic targets in
      the absence of clinical disease, such as platelet factor 4 in heparin-induced
      thrombocytopenia and beta(2)-glycoprotein-I (beta(2)GPI) in antiphospholipid
      syndrome. The presence of autoantibodies in the absence of disease suggests that
      conformational changes or other alterations in endogenous protein autoantigens
      are required for recognition by pathogenic autoantibodies. In thrombotic
      thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by
      autoantibodies likely depends on the balance between residual antigen, that is,
      enzyme activity, and demand imposed by local genesis of ultralarge multimers of
      von Willebrand factor. A corollary of these concepts is that disrupting platelet
      factor 4 and beta(2)GPI conformation (or ultralarge multimer of von Willebrand
      factor oligomerization or function) might provide a disease-targeted approach to
      prevent thrombosis without systemic anticoagulation or immunosuppression.
      Validation of this approach requires a deeper understanding of how seemingly
      normal host proteins become antigenic or undergo changes that increase antibody
      avidity, and how they can be altered to retain adaptive functions while shedding
      epitopes prone to elicit harmful autoimmunity.

PMID- 22966174
TI  - Relative biological effects of neutron mixed-beam irradiation for boron neutron
      capture therapy on cell survival and DNA double-strand breaks in cultured
      mammalian cells.
AB  - Understanding the biological effects of neutron mixed-beam irradiation used for
      boron neutron capture therapy (BNCT) is important in order to improve the
      efficacy of the therapy and to reduce side effects. In the present study, cell
      viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese
      hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80
      deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was
      significantly impaired in the neutron irradiation groups compared to the
      reference gamma-ray irradiation group. The relative biological effectiveness for
      10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There
      were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed
      beam and the gamma-ray groups. In addition, the size of the foci did not differ
      between groups. However, neutron mixed-beam irradiation resulted in foci with
      different spatial distributions. The foci were more proximal to each other in the
      neutron mixed-beam groups than the gamma-ray irradiation groups. These findings
      suggest that neutron beams may induce another type of DNA damage, such as
      clustered DNA-DSBs, as has been indicated for other high-LET irradiation.

PMID- 22966176
TI  - US officials warn 39 countries about risk of hantavirus among travellers to
      Yosemite.

PMID- 22966177
TI  - Uganda launches HPV vaccination programme to fight its commonest cancer.

PMID- 22966178
TI  - NHS needs some "creative destruction" to bring in new ways to deliver care, says
      think tank.

PMID- 22966180
TI  - Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of
      Clostridium difficile infection.
AB  - OBJECTIVES: First-line treatment options for Clostridium difficile infection
      (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the
      treatment of CDI. We compared the responses to NVB302 and vancomycin when used to
      treat simulated CDI in an in vitro gut model. METHODS: We used ceftriaxone to
      elicit simulated CDI in an in vitro gut model primed with human faeces.
      Vancomycin and NVB302 were instilled into separate gut models and the indigenous
      gut microbiota and C. difficile total viable counts, spores and toxin levels were
      monitored throughout. RESULTS: Ceftriaxone instillation promoted C. difficile
      germination and high-level toxin production. Commencement of NVB302 and
      vancomycin instillation reduced C. difficile total viable counts rapidly with
      only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin
      was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302
      instillation commenced in vessel 2 and 3, respectively, and remained undetectable
      for the remainder of the experiments. C. difficile spores were unaffected by the
      presence of vancomycin or NVB302. NVB302 treatment was associated with faster
      resolution of Bacteroides fragilis group. CONCLUSIONS: Both NVB302 and vancomycin
      were effective in treating simulated CDI in an in vitro gut model. C. difficile
      spore recrudescence was not observed following successful treatment with either
      NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the
      treatment of simulated CDI, and had less deleterious effects against B. fragilis
      group. NVB302 warrants further clinical investigation as a potentially novel
      antimicrobial agent for the treatment of CDI.

PMID- 22966181
TI  - The rise of emergency medicine in the sixties: paving a new entrance to the house
      of medicine.
AB  - Emergency medicine evolved into a medical specialty in the 1960s under the
      leadership of physicians in small communities across the country. This paper uses
      three case studies to investigate the political, societal, and local factors that
      propelled emergency medicine along this path. The case studies-Alexandria
      Hospital, Hartford Hospital, and Yale-New Haven Hospital-demonstrate that the
      changes in emergency medicine began at small community hospitals and later spread
      to urban teaching hospitals. These changes were primarily a response to public
      demand. The government, the American public, and the medical community brought
      emergency medical care to the forefront of national attention in the sixties.
      Simultaneously, patients' relationships with their general practitioners
      dissolved. As patients started to use the emergency room for non-urgent health
      problems, emergency visits increased astronomically. In response to rising
      patient loads and mounting criticism, hospital administrators devised strategies
      to improve emergency care. Drawing on hospital archives, oral histories, and
      statistical data, I will argue that small community hospitals' hiring of full
      time emergency physicians sparked the development of a new specialty. Urban
      teaching hospitals, which established triage systems and ambulatory care
      facilities, resisted the idea of emergency medicine and ultimately delayed its
      development. 

PMID- 22966182
TI  - Complete genome sequence of a Peste des petits ruminants virus recovered from
      wild bharal in Tibet, China.
AB  - For the first time, here we announce the complete genome sequence of a field
      isolate of Peste des petits ruminants virus (PPRV) derived from macerated rectal
      tissue of a free living bharal (Pseudois nayaur) that displayed clinical disease
      consistent with severe infection with PPRV. Further, we compare the full genome
      of this isolate, termed PPRV Tibet/Bharal/2008, with previously available PPRV
      genomes, including those of virus isolates from domestic small ruminants local to
      the area where the reported isolate was collected. The current sequence is
      phylogenetically classified as a lineage IV virus, sharing high levels of
      sequence identity with previously described Tibetan PPRV isolates. Indeed, across
      the entire genome, only 26 nucleotide differences (0.16% nucleotide variation)
      and, consequently, 9 amino acid changes were present compared to sequences of
      locally derived viruses.

PMID- 22966183
TI  - Complete genome sequence of a tenth human polyomavirus.
AB  - Nine polyomavirus (PyV) species are known to productively infect humans. The
      circular DNA genomes of PyVs are readily detectable using rolling circle
      amplification (RCA). RCA-based analysis of condyloma specimens from a patient
      with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
      demonstrated the presence of a tenth apparently human-tropic polyomavirus
      species, which we name HPyV10.

PMID- 22966184
TI  - Complete genome sequence of a novel human enterovirus C (HEV-C117) identified in
      a child with community-acquired pneumonia.
AB  - The new enterovirus C-117 strain belongs to the human enterovirus C species in
      the Picornaviridae family. We describe the characterization of the complete
      genome of this strain identified in a respiratory specimen of a child enrolled in
      the Community-Acquired Pneumonia Pediatric Research Initiative (CAP-PRI) study
      evaluating the etiology of community-acquired pneumonia (CAP).

PMID- 22966185
TI  - Complete genome sequence of a street rabies virus isolated from a rabid dog in
      China.
AB  - A rabies virus (RABV) was isolated from a dog in Anhui Province, China, in 2008.
      The virus was designated DRV-AH08. Its entire genome was sequenced and found to
      be closely related to RABV recently isolated in China and other Asian countries
      (homology of 87 to 98%) but distantly related to RABV in the "cosmopolitan" group
      (homology of 84 to 85%) in the clade I of RABV.

PMID- 22966186
TI  - Complete genome sequence of a street rabies virus from Mexico.
AB  - A canine rabies virus (RABV) has been used as a street rabies virus in laboratory
      investigations. Its entire genome was sequenced and found to be closely related
      to that of canine RABV circulating in Mexico. Sequence comparison indicates that
      the virus is closely related to those in the "cosmopolitan" group, with high
      homology (89 to 93%) to clade I of rabies viruses. The virus is now termed dog
      rabies virus-Mexico (DRV-Mexico).

PMID- 22966187
TI  - Complete genome sequence of bacteriophage SSU5 specific for Salmonella enterica
      serovar Typhimurium rough strains.
AB  - Salmonella enterica serovar Typhimurium rough strain-specific phage SSU5 was
      isolated, and its whole genome was sequenced. The 103,229-bp-long double-stranded
      DNA genome of SSU5 encodes 130 open reading frames with one tRNA for asparagine.
      Genomic analysis revealed that SSU5 might be the phylogenetic origin of cryptic
      plasmid pHCM2 harbored by Salmonella Typhi CT18.

PMID- 22966188
TI  - Complete genome sequence of a novel field strain of rearranged porcine circovirus
      type 2 in southern China.
AB  - We report here the complete genomic sequence of a novel porcine circovirus type 2
      (PCV2) strain, which is supposed to be the result of natural genetic
      recombination between the ORF1 gene of genotype PCV2b-1B and the ORF2 gene of
      PCV2b-1C. Further analyses revealed that this novel PCV2 strain arose from
      recombination between PCV2a and PCV2b strains within the ORF2 gene. To our
      knowledge, this is the first report of both inter- and intragenotype PCV2 gene
      rearrangement in the field, and it will help in understanding the epidemiology
      and molecular characteristics of porcine circovirus type 2(PCV2) in southern
      China.

PMID- 22966189
TI  - Complete genome sequence analysis of a recent chicken anemia virus isolate and
      comparison with a chicken anemia virus isolate from human fecal samples in China.
AB  - A new isolate of chicken anemia virus (CAV) was designated GD-1-12. GD-1-12 was
      isolated from a 12-day-old commercial broiler in Guangdong province, China, in
      2012. The GD-1-12 CAV caused high mortality, severe anemia, thymic atrophy, and
      subcutaneous hemorrhage in commercial broilers. Here, we report the complete
      genome sequence of GD-1-12 CAV and comparison with the complete genome sequence
      of another CAV that was isolated from human fecal samples in China (GenBank
      accession no. JQ690762). The genomes of the two CAV isolates shared high
      homology, although a deletion was identified by comparison. The findings from
      this study provide additional insights into the molecular characteristics of the
      CAV genomes and should advance knowledge for continuous monitoring and, perhaps,
      preventing the spread of the virus in chickens as well as in humans.

PMID- 22966190
TI  - Complete genome sequence of a novel porcine Sapelovirus strain YC2011 isolated
      from piglets with diarrhea.
AB  - Sapelovirus is a member of the family Picornaviridae and is emerging as an
      enteric porcine, simian, and avian pathogen. Here, we report the genome sequence
      of a novel porcine sapelovirus strain YC2011 isolated from piglets with severe
      diarrhea. The availability of the genome sequence is helpful to further
      investigations of molecular characteristics and epidemiology of porcine
      sapelovirus.

PMID- 22966191
TI  - Complete genomic sequence of Erwinia amylovora phage PhiEaH2.
AB  - Erwinia amylovora is the causative agent of fire blight, a serious disease of
      some Rosaceae plants. The newly isolated bacteriophage PhiEaH2 is able to lyse E.
      amylovora in the laboratory and has reduced the occurrence of fire blight cases
      in field experiments. This study presents the sequenced complete genome and
      analysis of phage PhiEaH2.

PMID- 22966192
TI  - Complete Genome Sequence of Aeromonas hydrophila Phage CC2.
AB  - Aeromonas hydrophila is one of the major pathogenic bacteria for fish and people.
      To develop an effective antimicrobial agent, we isolated a bacteriophage from
      sewage, named CC2, and sequenced its genome. Comparative genome analysis of phage
      CC2 with its relatives revealed that phage CC2 has higher sequence homology to A.
      salmonicida phage 65 than to A. hydrophila phage Aeh1. Here, we announce the
      complete genome sequence of CC2 and report major findings from the genomic
      analysis.

PMID- 22966193
TI  - Complete genome sequence of a recombinant coxsackievirus B4 from a patient with a
      fatal case of hand, foot, and mouth disease in Guangxi, China.
AB  - The coxsackievirus B4 (CVB4) belongs to human enterovirus B species within the
      family Picornaviridae. Here we report a novel complete genome sequence of a
      recombinant CVB4 strain, CVB4/GX/10, which was isolated from a patient with a
      fatal case of hand, foot, and mouth disease in China. The complete genome
      consists of 7,293 nucleotides, excluding the 3' poly(A) tail, and has an open
      reading frame that maps between nucleotide positions 742 and 7293 and encodes a
      2,183-amino-acid polyprotein. Phylogenetic analysis based on different genome
      regions reveals that CVB4/GX/10 is closest to a CVB4 strain, EPIHFMD-CLOSE
      CONTACT-16, in the 5' half (VP4~2B) of the genome, although it is closer to a
      Chinese CVB5 strain, CVB5/Henan/2010, in the 3' half (2C~3D) of the genome.
      Furthermore, similar bootscan analysis based on the whole genomes demonstrates
      that recombination has possibly occurred within the 2C domain and that CVB4/GX/10
      is a possible progeny of intertypic recombination of the CVB4 strain EPIHFMD
      CLOSE CONTACT-16 and CVB5/Henan/2010 that occurred during their cocirculation and
      evolution, which is a relatively common phenomenon in enteroviruses.

PMID- 22966194
TI  - Complete genome sequences of two Chinese virulent avian coronavirus infectious
      bronchitis virus variants.
AB  - Avian coronavirus infectious bronchitis virus (IBV) is variable, which causes
      many serotypes. Here we reported the complete genome sequences of two virulent
      IBV variants from China, GX-YL5 and GX-YL9, belonging to different serotypes.
      Differences between GX-YL5 and GX-YL9 were found mainly in stem-loop structure I
      in the predicted RNA secondary structure of open reading frame (ORF) 1b and the S
      protein gene fusion region, which will help us understand the molecular
      evolutionary mechanism of IBV and the disconcordance between the genotypes and
      serotypes of coronavirus.

PMID- 22966195
TI  - Complete genome sequences of two novel European clade bovine foamy viruses from
      Germany and Poland.
AB  - Bovine foamy virus (BFV), or bovine spumaretrovirus, is an infectious agent of
      cattle with no obvious disease association but high prevalence in its host. Here,
      we report two complete BFV sequences, BFV-Riems, isolated in 1978 in East
      Germany, and BFV100, isolated in 2005 in Poland. Both new BFV isolates share the
      overall genetic makeup of other foamy viruses (FV). Although isolated almost 25
      years apart and propagated in either bovine (BFV-Riems) or nonbovine (BFV100)
      cells, both viruses are highly related, forming the European BFV clade. Despite
      clear differences, BFV-Riems and BFV100 are still very similar to BFV isolates
      from China and the United States, comprising the non-European BFV clade. The
      genomic sequences presented here confirm the concept of high sequence
      conservation across most of the FV genome. Analyses of cell culture-derived
      genomes reveal that proviral DNA may specifically lack introns in the env-bel
      coding region. The spacing of the splice sites in this region suggests that BFV
      has developed a novel mode to express a secretory but nonfunctional Env protein.

PMID- 22966196
TI  - Complete genome sequence of an avian leukosis virus isolate associated with
      hemangioma and myeloid leukosis in egg-type and meat-type chickens.
AB  - Subgroup J avian leukosis virus (ALV-J) was first isolated from meat-type
      chickens that developed myeloid leukosis (ML). In recent years, field cases of
      hemangioma (HE) or HE and ML, rather than ML alone, have been reported in
      commercial layer flocks exposed to ALV-J with a high incidence in China. Here we
      report the complete genomic sequence of an ALV-J isolate that caused both HE and
      ML in egg-type and meat-type chickens in China. These findings will provide
      additional insights into the molecular characteristics in genomes, host range,
      and pathogenicity of ALV-J.

PMID- 22966197
TI  - Complete genome sequence of a monosense densovirus infecting the cotton bollworm,
      Helicoverpa armigera.
AB  - Densoviruses (DNVs) infecting arthropods are members of the family Parvoviridae.
      Here we report the complete genome sequence of a novel DNV with a monosense
      genome that infects cotton bollworms (Helicoverpa armigera), named HaDNV-1.
      Alignment and phylogenetic analysis revealed that HaDNV-1 showed high identity
      with the genus Iteravirus.

PMID- 22966198
TI  - Complete genome sequence of porcine epidemic diarrhea virus strain AJ1102
      isolated from a suckling piglet with acute diarrhea in China.
AB  - A diarrhea outbreak caused by porcine epidemic diarrhea virus (PEDV) has been
      observed in China since December 2010. We report here the complete genome
      sequence of PEDV strain AJ1102 isolated from a suckling piglet with acute
      diarrhea, which will help toward understanding the molecular and evolutionary
      characteristics of the epidemic PEDV in China.

PMID- 22966199
TI  - Complete genome sequence of avian tembusu-related virus strain WR isolated from
      White Kaiya ducks in Fujian, China.
AB  - Avian tembusu-related virus, which was first identified in China, is an emerging
      virus causing serious economic loss to the Chinese poultry industry. We report
      here the complete genome sequences of avian tembusu-related virus strain WR,
      isolated from a White Kaiya duck with disease characterized by an abrupt decrease
      in egg laying with ovarian hemorrhage, which will help in further understanding
      the molecular and evolutionary characteristics and pathogenesis of avian tembusu
      related virus, the new flavivirus affecting ducks in Southern China.

PMID- 22966200
TI  - The loss of RGS protein-Galpha(i2) interactions results in markedly impaired
      mouse neutrophil trafficking to inflammatory sites.
AB  - Neutrophils are first responders rapidly mobilized to inflammatory sites by a
      tightly regulated, nonredundant hierarchy of chemoattractants. These
      chemoattractants engage neutrophil cell surface receptors triggering
      heterotrimeric G-protein Galpha(i) subunits to exchange GDP for GTP. By limiting
      the duration that Galpha(i) subunits remain GTP bound, RGS proteins modulate
      chemoattractant receptor signaling. Here, we show that neutrophils with a genomic
      knock in of a mutation that disables regulator of G-protein signaling (RGS)
      Galpha(i2) interactions accumulate in the bone marrow and mobilize poorly to
      inflammatory sites. These defects are attributable to enhanced sensitivity to
      background signals, prolonged chemoattractant receptor signaling, and
      inappropriate CXCR2 downregulation. Intravital imaging revealed a failure of the
      mutant neutrophils to accumulate at and stabilize sites of sterile inflammation.
      Furthermore, these mice could not control a nonlethal Staphylococcus aureus
      infection. Neutrophil RGS proteins establish a threshold for Galpha(i)
      activation, helping to coordinate desensitization mechanisms. Their loss renders
      neutrophils functionally incompetent.

PMID- 22966201
TI  - Phosphorylation of the eukaryotic translation initiation factor 4E-transporter
      (4E-T) by c-Jun N-terminal kinase promotes stress-dependent P-body assembly.
AB  - Processing bodies (PBs, or P bodies) are cytoplasmic granules involved in mRNA
      storage and degradation that participate in the regulation of gene expression.
      PBs concentrate nontranslated mRNAs and several factors involved in mRNA decay
      and translational repression, including the eukaryotic translation initiation
      factor 4E-transporter (4E-T). 4E-T is required for PB assembly, but little is
      known about the molecular mechanisms that regulate its function. Here, we
      demonstrate that oxidative stress promotes multisite 4E-T phosphorylation. We
      show that the c-Jun N-terminal kinase (JNK) is targeted to PBs in response to
      oxidative stress and promotes the phosphorylation of 4E-T. Quantitative mass
      spectrometry analysis reveals that JNK phosphorylates 4E-T on six proline
      directed sites that are required for the formation of the 4E-T complex upon
      stress. We have developed an image-based computational method to quantify the
      size, number, and density of PBs in cells, and we find that while 4E-T is
      required for steady-state PB assembly, its phosphorylation facilitates the
      formation of larger PBs upon oxidative stress. Using polysomal mRNA profiling, we
      assessed global and specific mRNA translation but did not find that 4E-T
      phosphorylation impacts translational control. Collectively, these data support a
      model whereby PB assembly is regulated by a two-step mechanism involving a 4E-T
      dependent assembly stage in unstressed cells and a 4E-T phosphorylation-dependent
      aggregation stage in response to stress stimuli.

PMID- 22966202
TI  - Impact of CUX2 on the female mouse liver transcriptome: activation of female
      biased genes and repression of male-biased genes.
AB  - The growth hormone-regulated transcription factors STAT5 and BCL6 coordinately
      regulate sex differences in mouse liver, primarily through effects in male liver,
      where male-biased genes are upregulated and many female-biased genes are actively
      repressed. Here we investigated whether CUX2, a highly female-specific liver
      transcription factor, contributes to an analogous regulatory network in female
      liver. Adenoviral overexpression of CUX2 in male liver induced 36% of female
      biased genes and repressed 35% of male-biased genes. In female liver, CUX2 small
      interfering RNA (siRNA) preferentially induced genes repressed by adenovirus
      expressing CUX2 (adeno-CUX2) in male liver, and it preferentially repressed genes
      induced by adeno-CUX2 in male liver. CUX2 binding in female liver chromatin was
      enriched at sites of male-biased DNase hypersensitivity and at genomic regions
      showing male-enriched STAT5 binding. CUX2 binding was also enriched near genes
      repressed by adeno-CUX2 in male liver or induced by CUX2 siRNA in female liver
      but not at genes induced by adeno-CUX2, indicating that CUX2 binding is
      preferentially associated with gene repression. Nevertheless, direct CUX2 binding
      was seen at several highly female-specific genes that were positively regulated
      by CUX2, including A1bg, Cyp2b9, Cyp3a44, Tox, and Trim24. CUX2 expression and
      chromatin binding were high in immature male liver, where repression of adult
      male-biased genes and expression of adult female-biased genes are common,
      suggesting that the downregulation of CUX2 in male liver at puberty contributes
      to the developmental changes establishing adult patterns of sex-specific gene
      expression.

PMID- 22966203
TI  - Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular
      signals.
AB  - Initiation of transcription of RNA polymerase II (RNAPII)-dependent genes
      requires the participation of a host of basal transcription factors. Among genes
      requiring RNAPII for transcription, small nuclear RNAs (snRNAs) display a further
      requirement for a factor known as snRNA-activating protein complex (SNAPc). The
      scope of the biological function of SNAPc and its requirement for transcription
      of protein-coding genes has not been elucidated. To determine the genome-wide
      occupancy of SNAPc, we performed chromatin immunoprecipitation followed by high
      throughput sequencing using antibodies against SNAPC4 and SNAPC1 subunits.
      Interestingly, while SNAPC4 occupancy was limited to snRNA genes, SNAPC1
      chromatin residence extended beyond snRNA genes to include a large number of
      transcriptionally active protein-coding genes. Notably, SNAPC1 occupancy on
      highly active genes mirrored that of elongating RNAPII extending through the
      bodies and 3' ends of protein-coding genes. Inhibition of transcriptional
      elongation resulted in the loss of SNAPC1 from the 3' ends of genes, reflecting a
      functional association between SNAPC1 and elongating RNAPII. Importantly, while
      depletion of SNAPC1 had a small effect on basal transcription, it diminished the
      transcriptional responsiveness of a large number of genes to two distinct
      extracellular stimuli, epidermal growth factor (EGF) and retinoic acid (RA).
      These results highlight a role for SNAPC1 as a general transcriptional
      coactivator that functions through elongating RNAPII.

PMID- 22966204
TI  - Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3
      dependent control of the Bul arrestin-like adaptors.
AB  - Ubiquitylation of many plasma membrane proteins promotes their endocytosis
      followed by degradation in the lysosome. The yeast general amino acid permease,
      Gap1, is ubiquitylated and downregulated when a good nitrogen source like
      ammonium is provided to cells growing on a poor nitrogen source. This
      ubiquitylation requires the Rsp5 ubiquitin ligase and the redundant arrestin-like
      Bul1 and Bul2 adaptors. Previous studies have shown that Gap1 ubiquitylation
      involves the TORC1 kinase complex, which inhibits the Sit4 phosphatase. This
      causes inactivation of the protein kinase Npr1, which protects Gap1 against
      ubiquitylation. However, the mechanisms inducing Gap1 ubiquitylation after Npr1
      inactivation remain unknown. We here show that on a poor nitrogen source, the Bul
      adaptors are phosphorylated in an Npr1-dependent manner and bound to 14-3-3
      proteins that protect Gap1 against downregulation. After ammonium is added and
      converted to amino acids, the Bul proteins are dephosphorylated, dissociate from
      the 14-3-3 proteins, and undergo ubiquitylation. Furthermore, dephosphorylation
      of Bul requires the Sit4 phosphatase, which is essential to Gap1 downregulation.
      The data support the emerging concept that permease ubiquitylation results from
      activation of the arrestin-like adaptors of the Rsp5 ubiquitin ligase, this
      coinciding with their dephosphorylation, dissociation from the inhibitory 14-3-3
      proteins, and ubiquitylation.

PMID- 22966205
TI  - Distinct roles of DBHS family members in the circadian transcriptional feedback
      loop.
AB  - Factors interacting with core circadian clock components are essential to achieve
      transcriptional feedback necessary for metazoan clocks. Here, we show that all
      three members of the Drosophila behavior human splicing (DBHS) family of RNA
      binding proteins play a role in the mammalian circadian oscillator, abrogating or
      altering clock function when overexpressed or depleted in cells. Although these
      proteins are members of so-called nuclear paraspeckles, depletion of paraspeckles
      themselves via silencing of the structural noncoding RNA (ncRNA) Neat1 did not
      affect overall clock function, suggesting that paraspeckles are not required for
      DBHS-mediated circadian effects. Instead, we show that the proteins bound to
      circadian promoter DNA in a fashion that required the PERIOD (PER) proteins and
      potently repressed E-box-mediated transcription but not cytomegalovirus (CMV)
      promoter-mediated transcription when they were exogenously recruited.
      Nevertheless, mice with one or both copies of these genes deleted show only small
      changes in period length or clock gene expression in vivo. Data from transient
      transfections show that each of these proteins can either repress or activate,
      depending on the context. Taken together, our data suggest that all of the DBHS
      family members serve overlapping or redundant roles as transcriptional cofactors
      at circadian clock-regulated genes.

PMID- 22966207
TI  - Protein kinase C regulates late cell cycle-dependent gene expression.
AB  - The control of the cell cycle in eukaryotes is exerted in part by the coordinated
      action of a series of transcription factor complexes. This is exemplified by the
      Mcm1p-Fkh2p-Ndd1p complex in Saccharomyces cerevisiae, which controls the
      cyclical expression of the CLB2 cluster of genes at the G(2)/M phase transition.
      The activity of this complex is positively controlled by cyclin-dependent kinase
      (CDK) and polo kinases. Here, we demonstrate that the protein kinase Pkc1p works
      in the opposite manner to inhibit the activity of the Mcm1p-Fkh2p-Ndd1p complex
      and the expression of its target genes. In particular, Pkc1p causes
      phosphorylation of the coactivator protein Ndd1p. Reductions in Pkc1p activity
      and the presence of Pkc1p-insensitive Ndd1p mutant proteins lead to changes in
      the timing of CLB2 cluster expression and result in associated late cell cycle
      defects. This study therefore identifies an important role for Pkc1p in
      controlling the correct temporal expression of genes in the cell cycle.

PMID- 22966206
TI  - Upstream stimulatory factor 2 and hypoxia-inducible factor 2alpha (HIF2alpha)
      cooperatively activate HIF2 target genes during hypoxia.
AB  - While the functions of hypoxia-inducible factor 1alpha (HIF1alpha)/aryl
      hydrocarbon receptor nuclear translocator (ARNT) and HIF2alpha/ARNT (HIF2)
      proteins in activating hypoxia-inducible genes are well established, the role of
      other transcription factors in the hypoxic transcriptional response is less
      clear. We report here for the first time that the basic helix-loop-helix-leucine
      zip transcription factor upstream stimulatory factor 2 (USF2) is required for the
      hypoxic transcriptional response, specifically, for hypoxic activation of HIF2
      target genes. We show that inhibiting USF2 activity greatly reduces hypoxic
      induction of HIF2 target genes in cell lines that have USF2 activity, while
      inducing USF2 activity in cells lacking USF2 activity restores hypoxic induction
      of HIF2 target genes. Mechanistically, USF2 activates HIF2 target genes by
      binding to HIF2 target gene promoters, interacting with HIF2alpha protein, and
      recruiting coactivators CBP and p300 to form enhanceosome complexes that contain
      HIF2alpha, USF2, CBP, p300, and RNA polymerase II on HIF2 target gene promoters.
      Functionally, the effect of USF2 knockdown on proliferation, motility, and
      clonogenic survival of HIF2-dependent tumor cells in vitro is phenocopied by
      HIF2alpha knockdown, indicating that USF2 works with HIF2 to activate HIF2 target
      genes and to drive HIF2-depedent tumorigenesis.

PMID- 22966210
TI  - An Information Theory Approach to Nonlinear, Nonequilibrium Thermodynamics.
AB  - Using the problem of ion channel thermodynamics as an example, we illustrate the
      idea of building up complex thermodynamic models by successively adding physical
      information. We present a new formulation of information algebra that generalizes
      methods of both information theory and statistical mechanics. From this
      foundation we derive a theory for ion channel kinetics, identifying a
      nonequilibrium 'process' free energy functional in addition to the well-known
      integrated work functionals. The Gibbs-Maxwell relation for the free energy
      functional is a Green-Kubo relation, applicable arbitrarily far from equilibrium,
      that captures the effect of non-local and time-dependent behavior from transient
      thermal and mechanical driving forces. Comparing the physical significance of the
      Lagrange multipliers to the canonical ensemble suggests definitions of
      nonequilibrium ensembles at constant capacitance or inductance in addition to
      constant resistance. Our result is that statistical mechanical descriptions
      derived from a few primitive algebraic operations on information can be used to
      create experimentally-relevant and computable models. By construction, these
      models may use information from more detailed atomistic simulations. Two
      surprising consequences to be explored in further work are that
      (in)distinguishability factors are automatically predicted from the problem
      formulation and that a direct analogue of the second law for thermodynamic
      entropy production is found by considering information loss in stochastic
      processes. The information loss identifies a novel contribution from the
      instantaneous information entropy that ensures non-negative loss.

PMID- 22966208
TI  - Nonconserved Ca(2+)/calmodulin binding sites in Munc13s differentially control
      synaptic short-term plasticity.
AB  - Munc13s are presynaptic proteins that mediate synaptic vesicle priming and
      thereby control the size of the readily releasable pool of vesicles. During high
      synaptic activity, Munc13-1 and its closely related homolog, ubMunc13-2, bind
      Ca(2+)/calmodulin, resulting in enhanced priming activity and in changes of short
      term synaptic plasticity characteristics. Here, we studied whether bMunc13-2 and
      Munc13-3, two remote isoforms of Munc13-1 with a neuronal subtype-specific
      expression pattern, mediate synaptic vesicle priming and regulate short-term
      synaptic plasticity in a Ca(2+)/calmodulin-dependent manner. We identified a
      single functional Ca(2+)/calmodulin binding site in these isoforms and provide
      structural evidence that all Munc13s employ a common mode of interaction with
      calmodulin despite the lack of sequence homology between their Ca(2+)/calmodulin
      binding sites. Electrophysiological analysis showed that, during high-frequency
      activity, Ca(2+)/calmodulin binding positively regulates the priming activity of
      bMunc13-2 and Munc13-3, resulting in an increase in the size of the readily
      releasable pool of vesicles and subsequently in strong short-term synaptic
      enhancement of neurotransmission. We conclude that Ca(2+)/calmodulin-dependent
      regulation of priming activity is structurally and functionally conserved in all
      Munc13 proteins, and that the composition of Munc13 isoforms in a neuron
      differentially controls its short-term synaptic plasticity characteristics.

PMID- 22966211
TI  - Biocatalytic production of tetrahydroisoquinolines.
AB  - The promiscuity of the enzyme norcoclaurine synthase is described. This
      biocatalyst yielded a diverse array of substituted tetrahydroisoquinolines by
      cyclizing dopamine with various acetaldehydes in a Pictet-Spengler reaction. This
      enzymatic reaction may provide a biocatalytic route to a range of
      tetrahydroisoquinoline alkaloids.

PMID- 22966212
TI  - Glycemic control after total pancreatectomy for intraductal papillary mucinous
      neoplasm: an exploratory study.
AB  - Background. Glycemic control following total pancreatectomy (TP) has been thought
      to be difficult to manage. Diffuse intraductal papillary mucinous neoplasm (IPMN)
      is a potentially curable precursor to pancreatic adenocarcinoma, best treated by
      TP. Objective. Compare glycemic control in patients undergoing TP for IPMN to
      patients with type 1 diabetes mellitus (DM). Design/Setting. Retrospective
      cohort. Outcome Measure. Hemoglobin A1C(HbA1C) at 6, 12, 18, and 24 months after
      TP. In the control group, baseline was defined as 6 months prior to the first
      HbA1c measure. Results. Mean HgbA1C at each point of interest was similar between
      TP and type I DM patients (6 months (7.5% versus 7.7%, P = 0.52), 12 months (7.3%
      versus 8.0%, P = 0.081), 18 months (7.7% and 7.6%, P = 0.64), and at 24 months
      (7.3% versus 7.8%, P = 0.10)). Seven TP patients (50%) experienced a hypoglycemic
      event compared to 65 type 1 DM patients (65%, P = 0.38). Limitations. Small
      number of TP patients, retrospective design, lack of long-termfollowup.
      Conclusion. This suggests that glycemic control following TP for IPMNcan be well
      managed, similar to type 1 DM patients. Fear of DM following TP for IPMN should
      not preclude surgery when TP is indicated.

PMID- 22966213
TI  - Biochemical analysis of pentraxin 3 and fibrinogen levels in experimental
      periodontitis model.
AB  - OBJECTIVE: Pentraxin 3 (PTX3), newly discovered inflammation marker, is a member
      of acute-phase proteins. The hypothesis, synthesis of gingival tissue and serum
      PTX-3 increases in the experimental periodontitis model (with 10-day and 40-day
      periods), was tested by detecting gingival tissue and serum PTX-3 levels in rats
      with experimental periodontitis. METHODS: Thirty rats were randomly divided into
      three groups of ten animals each: ligature-induced experimental periodontitis
      groups (with 10-day (Group1) and 40-day periods (Group2)) and healthy group
      (Group3). At the end of experimental period, rats were sacrificed, and
      radiological and histomorphometric analyses were performed on the mandibles. PTX3
      levels were measured in gingival tissue and serum samples using ELISA. Plasma
      fibrinogen levels were measured according to the nephelometric method. RESULTS:
      Significant alveolar bone resorption and periodontal inflammation were evident in
      periodontitis groups. Levels of PTX3 in gingival tissue were statistically higher
      in Group 1 than those in groups 2 and 3 (P < 0.01). No significant difference was
      found in serum PTX3 levels between experimental periodontitis and control groups
      (P > 0.05). Plasma fibrinogen levels were significantly increased in the
      experimental periodontitis groups (P < 0.001). CONCLUSION: PTX3 seems to be
      associated with tissue destruction in earlier periods of inflammatory periodontal
      disease, contrary to the fibrinogen findings.

PMID- 22966214
TI  - Both acute and chronic placental inflammation are overrepresented in term
      stillbirths: a case-control study.
AB  - OBJECTIVE: To elucidate differences in the frequency and severity of acute
      chorioamnionitis (CAM) and chronic villitis in placentas from stillborns compared
      with liveborns at term and to evaluate other risk factors and placental findings.
      DESIGN: Case-control study. SETTING: All delivery wards in major Stockholm area.
      Population or Sample. Placentas from stillborn/case (n = 126) and
      liveborn/control (n = 273) neonates were prospectively collected between 2002 and
      2005. METHODS: CAM was assessed on a three-grade scale based on the presence and
      distribution of polymorphonuclear leucocytes in the chorion/amnion. The presence
      of vasculitis and funisitis was recorded separately. Chronic villitis was
      diagnosed by the presence of mononuclear cells in the villous stroma. Relevant
      clinical data were collected from a specially constructed, web-based database.
      The statistic analyses were performed using multivariable logistic regression.
      RESULTS: CAM (especially severe, AOR: 7.39 CI: 3.05-17.95), villous immaturity
      (AOR: 7.17 CI: 2.66-19.33), villitis (<1 % AOR: 4.31 CI: 1.16-15.98; >= 1 %, AOR:
      3.87 CI: 1.38-10.83), SGA (AOR: 7.52 CI: 3.06-18.48), and BMI >24.9 (AOR: 2.06
      CI: 1.21-3.51) were all connected to an elevated risk of term stillbirth.
      CONCLUSIONS: We found that CAM, chronic villitis, villous immaturity, SGA, and
      maternal overweight, but not vasculitis or funisitis are independently associated
      with risk for stillbirth at term.

PMID- 22966215
TI  - A systematic review of the recent quality of life studies in adult extremity
      sarcoma survivors.
AB  - Background. Extremity sarcoma represents a heterogeneous group of rare cancers
      that carries a relatively high morbidity with regards to physical function.
      Quality of Life (QoL) as an outcome is an important consideration in this cohort.
      We aimed to identify the correlates of QoL in extremity sarcoma cohorts. Methods.
      A systematic review of the literature on extremity sarcoma in adults from five
      databases over the last ten years was undertaken. Results. Twelve articles were
      chosen and assessed for quality. Physical and social function of extremity
      sarcoma survivors is below that of the general population. Overall QoL scores of
      these patients are comparable to those of the general population. Studies that
      used more recently treated cohorts found that patients who had limb sparing
      surgery displayed superior functional outcomes over those that underwent
      amputations. Pain and perceiving that the cancer negatively influenced
      opportunities was associated with poor outcomes. Conclusion. The available
      literature regarding QoL in extremity sarcoma patients is heterogeneous in terms
      of aims and assessment tools. Results need to be interpreted in light of the
      improved management of extremity sarcoma in more recent patient cohorts.

PMID- 22966216
TI  - Imaging features of superficial and deep fibromatoses in the adult population.
AB  - The fibromatoses are a group of benign fibroblastic proliferations that vary from
      benign to intermediate in biological behavior. This article will discuss imaging
      characteristics and patient demographics of the adult type superficial (fascial)
      and deep (musculoaponeurotic) fibromatoses. The imaging appearance of these
      lesions can be characteristic (particularly when using magnetic resonance
      imaging). Palmar fibromatosis demonstrates multiple nodular or band-like soft
      tissue masses arising from the proximal palmar aponeurosis and extending along
      the subcutaneous tissues of the finger in parallel to the flexor tendons. T1 and
      T2-weighted signal intensity can vary from low (higher collagen) to intermediate
      (higher cellularity), similar to the other fibromatoses. Plantar fibromatosis
      manifests as superficial lesions along the deep plantar aponeurosis, which
      typically blend with the adjacent plantar musculature. Linear tails of extension
      ("fascial tail sign") along the aponeurosis are frequent. Extraabdominal and
      abdominal wall fibromatosis often appear as a heterogeneous lesion with low
      signal intensity bands on all pulse sequences and linear fascial extensions
      ("fascial tail" sign) with MR imaging. Mesenteric fibromatosis usually
      demonstrates a soft tissue density on CT with radiating strands projecting into
      the adjacent mesenteric fat. When imaging is combined with patient demographics,
      a diagnosis can frequently be obtained.

PMID- 22966217
TI  - Extra-abdominal desmoid tumours: a review of the literature.
AB  - Extra-abdominal desmoid lesions, otherwise known as aggressive fibromatosis, are
      slow-growing benign lesions which may be encountered in clinical practice. Recent
      controversies exist regarding their optimal treatment. Given their benign nature,
      is major debulking surgery justified, or is it worth administering chemotherapy
      for a disease process which unusually defies common teaching and responds to such
      medications? We present a literature review of this particular pathology
      discussing the aetiology, clinical presentation, and various current
      controversies in the treatment options.

PMID- 22966218
TI  - SOD-Mimic Cu(II) Dimeric Complexes Involving Kinetin and Its Derivative:
      Preparation and Characterization.
AB  - Two SOD-mimic active dimeric Cu(II) chlorido complexes of the compositions
      [Cu(2)(MU-HL(1))(4)Cl(2)]Cl(2) (1) and [Cu(2)(MU-HL(2))(2)(MU
      Cl)(2)(HL(2))(2)Cl(2)] . 4H(2)O (2) involving the cosmetologically relevant
      cytokinin kinetin (N6-furfuryladenine, HL(1)) and its derivative N6-(5
      methylfurfuryl)adenine (HL(2)) have been synthesized and characterized by
      elemental analysis, infrared, and electronic spectroscopy, ESI+ mass
      spectrometry, conductivity and temperature dependence of magnetic susceptibility
      measurements, and thermogravimetric (TG) and differential thermal (DTA) analyses.
      The results of these methods, particularly the temperature dependence of magnetic
      susceptibility, showed the complexes to be dimeric with a strong
      antiferromagnetic exchange (J = -290 cm(-1) for complex 1 and J = -160 cm(-1) for
      2). The complexes have been identified as auspicious SOD-mimics, as their
      antiradical activity evaluated by the in vitro SOD-mimic assay resulted in the
      IC(50) values equal to 8.13 MUM (1) and 0.71 MUM (2).

PMID- 22966220
TI  - The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils.
AB  - PPARgamma agonists can either enhance or inhibit eosinophil migration, which is a
      sum of directional migration (chemotaxis) and random cell movement
      (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not
      been examined. This study investigates the effects of PPARalpha, delta, and gamma
      agonists on eosinophil migration and chemokinesis. Eosinophils purified from
      blood of atopic donors were preincubated with rosiglitazone (PPARgamma agonist),
      GW9578 (PPARalpha agonist), GW501516 (PPARdelta agonist), or diluent. The effects
      of PPAR agonists were examined on eosinophil chemokinesis, eotaxin-induced
      migration of eosinophils, and migration of IL-5Ralpha+ CD34+ cells. Expressions
      of CCR3, phospho-p38, phospho-ERK, and calcium release were also measured in
      eosinophils after rosiglitazone treatment. Low concentrations of rosiglitazone,
      but not GW9578 or GW501516, increased chemokinesis of eosinophils (P = 0.0038),
      and SDF-1alpha-induced migration of immature eosinophils (P = 0.0538).
      Rosiglitazone had an effect on eosinophil calcium flux but had no effect on
      expression of CCR3 or phosphorylation of p38 or ERK. In contrast, high
      concentrations of rosiglitazone inhibited eosinophil migration (P = 0.0042). The
      effect of rosiglitazone on eosinophil migration and chemokinesis appears to be
      through modification of calcium signaling, which alludes to a novel PPAR-mediated
      mechanism to modulate eosinophil function.

PMID- 22966219
TI  - Arterial Spin Labeling (ASL) fMRI: advantages, theoretical constrains, and
      experimental challenges in neurosciences.
AB  - Cerebral blood flow (CBF) is a well-established correlate of brain function and
      therefore an essential parameter for studying the brain at both normal and
      diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique
      that uses arterial water as an endogenous tracer to measure CBF. ASL provides
      reliable absolute quantification of CBF with higher spatial and temporal
      resolution than other techniques. And yet, the routine application of ASL has
      been somewhat limited. In this review, we start by highlighting theoretical
      complexities and technical challenges of ASL fMRI for basic and clinical
      research. While underscoring the main advantages of ASL versus other techniques
      such as BOLD, we also expound on inherent challenges and confounds in ASL
      perfusion imaging. In closing, we expound on several exciting developments in the
      field that we believe will make ASL reach its full potential in neuroscience
      research.

PMID- 22966221
TI  - PPARs and HCV-Related Hepatocarcinoma: A Mitochondrial Point of View.
AB  - Hepatitis-C-virus-related infective diseases are worldwide spread pathologies
      affecting primarily liver. The infection is often asymptomatic, but when
      chronically persisting can lead to liver scarring and ultimately to cirrhosis,
      which is generally apparent after decades. In some cases, cirrhosis will progress
      to develop liver failure, liver cancer, or life-threatening esophageal and
      gastric varices. HCV-infected cells undergo profound metabolic dysregulation
      whose mechanisms are yet not well understood. An emerging feature in the
      pathogenesis of the HCV-related disease is the setting of a pro-oxidative
      condition caused by dysfunctions of mitochondria which proved to be targets of
      viral proteins. This causes deregulation of mitochondria-dependent catabolic
      pathway including fatty acid oxidation. Nuclear receptors and their ligands are
      fundamental regulators of the liver metabolic homeostasis, which are disrupted
      following HCV infection. In this contest, specific attention has been focused on
      the peroxisome proliferator activated receptors given their role in controlling
      liver lipid metabolism and the availability of specific pharmacological drugs of
      potential therapeutic utilization. However, the reported role of PPARs in HCV
      infection provides conflicting results likely due to different species-specific
      contests. In this paper we summarize the current knowledge on this issue and
      offer a reconciling model based on mitochondria-related features.

PMID- 22966222
TI  - PPARgamma Ligands Regulate Noncontractile and Contractile Functions of Airway
      Smooth Muscle: Implications for Asthma Therapy.
AB  - In asthma, the increase in airway smooth muscle (ASM) can contribute to
      inflammation, airway wall remodeling and airway hyperresponsiveness (AHR).
      Targetting peroxisome proliferator-activated receptor gamma (PPARgamma), a
      receptor upregulated in ASM in asthmatic airways, may provide a novel approach to
      regulate these contributions. This review summarises experimental evidence that
      PPARgamma ligands, such as rosiglitazone (RGZ) and pioglitazone (PGZ), inhibit
      proliferation and inflammatory cytokine production from ASM in vitro. In
      addition, inhaled administration of these ligands reduces inflammatory cell
      infiltration and airway remodelling in mouse models of allergen-induced airways
      disease. PPARgamma ligands can also regulate ASM contractility, with acute
      treatment eliciting relaxation of mouse trachea in vitro through a PPARgamma
      independent mechanism. Chronic treatment can protect against the loss of
      bronchodilator sensitivity to beta(2)-adrenoceptor agonists and inhibit the
      development of AHR associated with exposure to nicotine in utero or following
      allergen challenge. Of particular interest, a small clinical trial has shown that
      oral RGZ treatment improves lung function in smokers with asthma, a group that is
      generally unresponsive to conventional steroid treatment. These combined findings
      support further investigation of the potential for PPARgamma agonists to target
      the noncontractile and contractile functions of ASM to improve outcomes for
      patients with poorly controlled asthma.

PMID- 22966223
TI  - Time-Qualified Patterns of Variation of PPARgamma, DNMT1, and DNMT3B Expression
      in Pancreatic Cancer Cell Lines.
AB  - Carcinogenesis is related to the loss of homeostatic control of cellular
      processes regulated by transcriptional circuits and epigenetic mechanisms. Among
      these, the activities of peroxisome proliferator-activated receptors (PPARs) and
      DNA methyltransferases (DNMTs) are crucial and intertwined. PPARgamma is a key
      regulator of cell fate, linking nutrient sensing to transcription processes, and
      its expression oscillates with circadian rhythmicity. Aim of our study was to
      assess the periodicity of PPARgamma and DNMTs in pancreatic cancer (PC). We
      investigated the time-related patterns of PPARG, DNMT1, and DNMT3B expression
      monitoring their mRNA levels by qRT-PCR at different time points over a 28-hour
      span in BxPC-3, CFPAC-1, PANC-1, and MIAPaCa-2 PC cells after synchronization
      with serum shock. PPARG and DNMT1 expression in PANC-1 cells and PPARG expression
      in MIAPaCa-2 cells were characterized by a 24 h period oscillation, and a
      borderline significant rhythm was observed for the PPARG, DNMT1, and DNMT3B
      expression profiles in the other cell lines. The time-qualified profiles of gene
      expression showed different shapes and phase relationships in the PC cell lines
      examined. In conclusion, PPARG and DNMTs expression is characterized by different
      time-qualified patterns in cell lines derived from human PC, and this
      heterogeneity could influence cell phenotype and human disease behaviour.

PMID- 22966224
TI  - Update on ppargamma and nonalcoholic Fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common initial presentation
      of obesity and insulin resistance. Uninterrupted progression of hepatic lipid
      accumulation often leads to fatty liver disease and eventually cirrhosis. Insulin
      resistance is one of the characteristics of type 2 diabetes. Several types of
      treatment have been employed against type 2 diabetes some of which ameliorate
      NAFLD. The frequent line of treatment to improve insulin sensitivity is the use
      of thiazolidinediones (TZD) which activate the nuclear receptor, peroxisome
      proliferator activated receptor gamma (Ppargamma). Although TZDs are proven to be
      very effective in promoting insulin sensitivity, its actions on Ppargamma have
      been complicated, specifically on NAFLD. According to studies in different
      models, Ppargamma manifests both beneficial and undesirable effects on NAFLD.
      This paper will focus on the current knowledge of Ppargamma and its effect on
      NAFLD.

PMID- 22966226
TI  - Peroxisome Proliferator-Activated Receptor alpha Plays an Important Role in the
      Expression of Monocyte Chemoattractant Protein-1 and Neointimal Hyperplasia after
      Vascular Injury.
AB  - Peroxisome proliferator-activated receptor alpha is a member of the nuclear
      receptor superfamily. It modulates smooth muscle cell proliferation and
      inflammatory cytokines in vitro. In this study, we tested the hypothesis that
      PPARalpha would decrease the expression of monocyte chemoattractant protein-1 and
      tissue factor, and inhibit neointimal formation in a murine double carotid artery
      injury model. Carotid artery injury was performed in the PPARalpha knockout and
      wild type (WT) mice, treated and untreated with Wy14643, a PPARalpha activator.
      Up-regulated MCP-1 and TF expression and more neointimal formation were observed
      in the PPARalpha(-/-) mice compared with WT mice. The activation of PPARalpha
      resulted in further decreased neointimal formation. Our data further suggest that
      the decrease in neointimal formation is due to down-regulation of MCP-1 by
      PPARalpha resulting in decreased leukocyte infiltration and TF expression.

PMID- 22966227
TI  - The Use of Albuterol in Young Infants Hospitalized with Acute RSV Bronchiolitis.
AB  - Objective. To evaluate the effects of albuterol use in young infants admitted
      with respiratory syncytial virus (RSV) bronchiolitis with regards to length of
      time on supplemental oxygen and length of stay (LOS). To consider the possibility
      that albuterol use may increase the need for supplemental oxygen and increase
      LOS. Design, Setting, and Participants. Full-term infants between the ages of 11
      days and 90 days (N = 316) were included in this retrospective study. Infants
      included were hospitalized with a diagnosis of RSV bronchiolitis at a university
      affiliated children's hospital. Results. In 4 of 5 severity groups, patients who
      received albuterol required more time on supplemental oxygen and had longer LOS.
      The differences only reached statistical significance in one of the severity
      groups in regards to LOS. Conclusions. The use of albuterol does not appear to be
      useful in the treatment of young infants with RSV bronchiolitis and may actually
      be harmful, in regards to increased supplemental oxygen need.

PMID- 22966225
TI  - The Key to Unlocking the Chemotherapeutic Potential of PPARgamma Ligands: Having
      the Right Combination.
AB  - Despite extensive preclinical evidence that peroxisome proliferator-activated
      receptor (PPAR)gamma activation protects against tumourigenesis, results from a
      few clinical trials using PPARgamma ligands as monotherapy show modest success.
      In spite of this, several groups reported exciting results with therapeutic
      regimens that combine PPARgamma ligands with other compounds: chemotherapeutic
      agents, retinoid x receptor (RXR)alpha agonists, statins, or cell-to-cell
      signaling molecules in preclinical cancer models and human trials. Here we have
      compiled an extensive review, consolidating the existing literature, which
      overwhelmingly supports a beneficial effect of treating with PPARgamma ligands in
      combination with existing chemotherapies versus their monotherapy in cancer.
      There are many examples in which combination therapy resulted in
      synergistic/additive effects on apoptosis, differentiation, and the ability to
      reduce cell growth and tumour burden. There are also studies that indicate that
      PPARgamma ligand pretreatment overcomes resistance and reduces toxicities.
      Several mechanisms are explored to explain these protective effects. This paper
      highlights each of these studies that, collectively, make a very strong case for
      the use of PPARgamma ligands in combination with other agents in the treatment
      and management of several cancers.

PMID- 22966228
TI  - The Effect of Puberty on Interaction between Vitamin D Status and Insulin
      Resistance in Obese Asian-Indian Children.
AB  - To study the effect of puberty on the relationship between serum 25
      hydroxyvitamin D (25(OH)D) and parameters of insulin kinetics in obese Asian
      Indian children. Material and Methods. The study population included 62 obese
      Asian-Indian children and adolescents in the age group of 6-17 years. Blood
      glucose, serum insulin, and serum 25(OH)D were measured. Total body fat was
      measured by dual energy X-ray absorptiometry. Indices of insulin resistance (HOMA
      IR, AUC for insulin) and sensitivity (WBISI) were calculated after oral glucose
      tolerance test. Result. A total of 62 subjects (35 boys; mean age = 13.0 +/- 3
      years; BMI = 29.3 +/- 4.8 kg/sq M; 19 subjects in Tanner stage 1, 11 in stage 2,
      6 in stage 3, 3 in stage 4, and 23 subjects in Tanner stage 5) were studied. All
      study subjects were vitamin D deficient with a mean serum 25(OH)D of 8.5 +/- 4.2
      ng/mL. No significant relationship was observed between serum 25(OH)D and
      parameters of insulin kinetics in prepubertal children. However, a significant
      inverse correlation was seen between serum 25(OH)D and HOMAIR (r = -0.41, P =
      0.03) in postpubertal subjects. Conclusion. The relationship between vitamin D
      status and parameters of insulin kinetics are affected by puberty.

PMID- 22966229
TI  - An Optimized Adsorbent Sampling Combined to Thermal Desorption GC-MS Method for
      Trimethylsilanol in Industrial Environments.
AB  - Trimethylsilanol (TMSOH) can cause damage to surfaces of scanner lenses in the
      semiconductor industry, and there is a critical need to measure and control
      airborne TMSOH concentrations. This study develops a thermal desorption (TD)-gas
      chromatography (GC)-mass spectrometry (MS) method for measuring trace-level TMSOH
      in occupational indoor air. Laboratory method optimization obtained best
      performance when using dual-bed tube configuration (100 mg of Tenax TA followed
      by 100 mg of Carboxen 569), n-decane as a solvent, and a TD temperature of 300
      degrees C. The optimized method demonstrated high recovery (87%), satisfactory
      precision (<15% for spiked amounts exceeding 1 ng), good linearity (R(2) =
      0.9999), a wide dynamic mass range (up to 500 ng), low method detection limit
      (2.8 ng m(-3) for a 20-L sample), and negligible losses for 3-4-day storage. The
      field study showed performance comparable to that in laboratory and yielded first
      measurements of TMSOH, ranging from 1.02 to 27.30 MUg/m(3), in the semiconductor
      industry. We suggested future development of real-time monitoring techniques for
      TMSOH and other siloxanes for better maintenance and control of scanner lens in
      semiconductor wafer manufacturing.

PMID- 22966231
TI  - Total ossiculoplasty: advantages of two-point stabilization technique.
AB  - Objective. Evaluate a porous polyethylene prosthesis with two-point stabilization
      in total ossiculoplasty. This approach utilizes a lateral as well as a medial
      graft to stabilize a total ossicular prosthesis (TOP). Study Design.
      Retrospective cohort review of total ossiculoplasty. Methods. All patients who
      underwent total ossiculoplasty during the years 2004-2007 were included in the
      study group. Only five patients (10%) had primary surgery whereas 45 (90%)
      underwent revision surgery. Cartilage grafts covering the prosthesis (Sheehy,
      Xomed) laterally were used in all patients with areolar tissue being used for
      medial stabilization at the stapes footplate. Follow-up examination and
      audiometrics were performed a mean of 8.1 months following surgery. Results. The
      percentage of patients closing their ABG to within 10 dB was 44% with 66% closing
      their ABG to within 20 dB. The mean four-frequency hearing gain was 15.7 dB. The
      mean postoperative ABG was 15.7 dB. Conclusion. Audiometric results following
      total ossiculoplasty surgery using two-point stabilization exceeded results from
      the otologic literature. Proper two-point fixation with areolar tissue and
      stabilization utilizing cartilage were the keys to achieving a relatively high
      percentage of success in chronic ear disease in this sample.

PMID- 22966230
TI  - Molecular Regulation of the Mitochondrial F(1)F(o)-ATPsynthase: Physiological and
      Pathological Significance of the Inhibitory Factor 1 (IF(1)).
AB  - In mammals, the mitochondrial F(1)F(o)-ATPsynthase sets out the energy
      homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws
      of thermodynamics command it; however, it is privileged to have a dedicated
      molecular regulator that controls its rotation. This is the so-called ATPase
      Inhibitory Factor 1 (IF(1)) that blocks its reversal to avoid the consumption of
      cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also
      demonstrated that IF(1) may control the alignment of the enzyme along the
      mitochondrial inner membrane, thus increasing the interest for the molecule. We
      conceived this review to outline the fundamental knowledge of the F(1)F(o)
      ATPsynthase and link it to the molecular mechanisms by which IF(1) regulates its
      way of function, with the ultimate goal to highlight this as an important and
      possibly unique means to control this indispensable enzyme in both physiological
      and pathological settings.

PMID- 22966232
TI  - Pathologies Associated with Serum IgG4 Elevation.
AB  - Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an
      increase of serum IgG4 levels. However other conditions have also been associated
      to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our
      hospital over a one-year period were analyzed. When IgG4 level were over 1.35
      g/L, the patient's clinical observation was analyzed and both final diagnosis and
      reason leading to IgG subclasses analysis were recorded. Only polyclonal
      increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass
      analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis
      associated to serum IgG4 increase was very variable. Most patients (25%)
      presented with repeated infections, 13.5% with autoimmune diseases, and 10% with
      IgG4-RD. Other patients presented with cancer, primary immune deficiencies,
      idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic
      vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean
      IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies
      associated to elevated IgG4 levels. Conclusions. Our study confirms that
      elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD
      diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological
      conditions should be excluded.

PMID- 22966233
TI  - Treatment of moyamoya syndrome associated with systemic lupus erythematosus and
      hypothyroidism in an adult by encephaloduroarteriosynangiosis: a case report.
AB  - A 54-year-old woman presented to our hospital with progressive motor weakness of
      the right arm. She had a medical history of systemic lupus erythematosus (SLE)
      and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction
      of the left hemisphere. Cervical echogram indicated severe stenosis of the
      internal carotid artery (ICA) without wall thickening. Cerebral angiography
      indicated left ICA occlusion, development of unilateral moyamoya vessels, and
      leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed
      after cerebral (99) (m)Technetium-ethyl-cysteinate-dimer single-photon emission
      computed tomography indicated a decreased cerebral blood flow, diminished
      cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months
      after surgery. Moyamoya syndrome is a rare complication of both SLE and
      hypothyroidism, and the surgical indication remains controversial. By evaluating
      the decreased cerebral perfusion reserve capacity and the existence of
      leptomeningeal anastomosis, EDAS could be an efficient method for the treatment
      of moyamoya syndrome associated with SLE and hypothyroidism.

PMID- 22966234
TI  - A case of drug reaction with eosinophilia and systemic symptoms.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterized by
      fever, skin rash, hematological abnormalities, and systemic involvement such as
      hepatitis. DRESS usually presents 2-6 weeks after drug initiation. DRESS should
      be suspected on clinical grounds in the setting of the introduction of new drug
      therapy and is most commonly described after the introduction of aromatic
      anticonvulsants, allopurinol, or antiretroviral therapies. We describe here a
      case of DRESS due to phenytoin exposure with complete resolution on drug
      discontinuation. Our patient developed DRESS with a skin rash, lymphadenopathy,
      and markedly abnormal liver enzymes, 4 weeks after drug initiation following
      drainage of a brain abscess. He was initially diagnosed as having a recurrence of
      the abscess or sepsis of another origin. It is important to recognise the
      possibility of DRESS in this setting, as a good outcome depends on the immediate
      withdrawal of the offending drug. A mortality rate of up to 10% has been
      described in unrecognised cases.

PMID- 22966235
TI  - Retinal Pigment Epithelium and Muller Progenitor Cell Interaction Increase Muller
      Progenitor Cell Expression of PDGFRalpha and Ability to Induce Proliferative
      Vitreoretinopathy in a Rabbit Model.
AB  - Purpose. Proliferative vitreoretinopathy (PVR) is a complication of retinal
      detachment characterized by redetachment of the retina as a result of membrane
      formation and contraction. A variety of retinal cells, including retinal pigment
      epithelial (RPE) and Muller glia, and growth factors may be responsible. Platelet
      derived growth factor receptor alpha (PDGFRalpha) is found in large quantities in
      PVR membranes, and is intrinsic to the development of PVR in rabbit models. This
      study explores the expression of PDGFR in cocultures of RPE and Muller cells over
      time to examine how these two cell types may collaborate in the development of
      PVR. We also examine how changes in PDGFRalpha expression alter Muller cell
      pathogenicity. Methods. Human MIO-M1 Muller progenitor (MPC) and ARPE19 cells
      were studied in a transmembrane coculture system. Immunocytochemistry and Western
      blot were used to look at PDGFRalpha, PDGFRbeta, and GFAP expression. A
      transfected MPC line cell line expressing the PDGFRalpha (MIO-M1alpha) was
      generated, and tested in a rabbit model for its ability to induce PVR. Results.
      The expression of PDGFRalpha and PDGFRbeta was upregulated in MIO-M1 MPCs
      cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression
      of PDGFRalpha in the MIO-M1 cell line resulted in increased pathogenicity and
      enhanced ability to induce PVR in a rabbit model. Conclusions. Muller and RPE
      cell interaction can lead to upregulation of PDGFRalpha and increased Muller cell
      pathogenicity. Muller cells may play a more active role than previously thought
      in the development of PVR membranes, particularly when stimulated by an RPE-cell
      rich environment. Additional studies of human samples and in animal models are
      warranted.

PMID- 22966236
TI  - Human embryonic stem cell responses to ionizing radiation exposures: current
      state of knowledge and future challenges.
AB  - Human embryonic stem cells, which are derived from the inner cell mass of the
      blastocyst, have become an object of intense study over the last decade. They
      possess two unique properties that distinguish them from many other cell types:
      (i) the ability to self-renew indefinitely in culture under permissive
      conditions, and (ii) the pluripotency, defined as the capability of giving rise
      to all cell types of embryonic lineage under the guidance of the appropriate
      developmental cues. The focus of many recent efforts has been on the elucidating
      the signaling pathways and molecular networks operating in human embryonic stem
      cells. These cells hold great promise in cell-based regenerative therapies,
      disease modeling, drug screening and testing, assessing genotoxic and mutagenic
      risks associated with exposures to a variety of environmental factors, and so
      forth. Ionizing radiation is ubiquitous in nature, and it is widely used in
      diagnostic and therapeutic procedures in medicine. In this paper, our goal is to
      summarize the recent progress in understanding how human embryonic stem cells
      respond to ionizing radiation exposures, using novel methodologies based on
      "omics" approaches, and to provide a critical discussion of what remains unknown;
      thus proposing a roadmap for the future research in this area.

PMID- 22966237
TI  - Functional multipotency of stem cells: what do we need from them in the heart?
AB  - After more than ten years of human research in the field of cardiac regenerative
      medicine, application of stem cells in different phases of ischemic heart disease
      has come to age. Randomized clinical trials have demonstrated that stem cell
      therapy can improve cardiac recovery after the acute phase of myocardial ischemia
      and in patients with chronic ischemic heart disease, and several efficacy phase
      III trials with clinical endpoints are on their way. Nevertheless, a complete
      knowledge on the mechanisms of action of stem cells still remains elusive. Of the
      three main mechanisms by which stem cells could exert their benefit, paracrine
      signaling from the administered cells and stimulation of endogenous repair are
      nowadays the most plausible ones. However, in this review we will define and
      discuss the concept of stem cell potency and differentiation, will examine the
      evidence available, and will depict future directions of research.

PMID- 22966238
TI  - Periostin as a biomarker of the amniotic membrane.
AB  - Tracing the precise developmental origin of amnion and amnion-derived stem cells
      is still challenging and depends chiefly on analyzing powerful genetic model
      amniotes like mouse. Profound understanding of the fundamental differences in
      amnion development in both the disc-shaped primate and human embryo and the cup
      shaped mouse embryo is pivotal in particular when sampling amniotic membrane from
      nonprimate species for isolating candidate amniotic stem cells. The availability
      of molecular marker genes that are specifically expressed in the amniotic
      membrane and not in other extraembryonic membranes would be instrumental to
      validate unequivocally the starting material under investigation. So far such
      amniotic markers have not been reported. We postulated that bone morphogenetic
      protein (BMP) target genes are putative amniotic membrane markers mainly because
      deficiency in one of several components of the BMP signaling cascade in mice has
      been documented to result in defective development of the early amnion.
      Comparative gene expression analysis of acknowledged target genes for BMP in
      different extraembryonic tissues, combined with in situ hybridization, identified
      Periostin (Postn) mRNA enrichment in amnion throughout gestation. In addition, we
      identify and propose a combination of markers as transcriptional signature for
      the different extraembryonic tissues in mouse.

PMID- 22966239
TI  - Restoration of innate and adaptive immune responses by HCV viral inhibition with
      an induction approach using natural interferon-beta in chronic hepatitis C.
AB  - Chronic hepatitis C (CHC) is a serious medical problem necessitating more
      effective treatment. This study investigated the hypothesis that an induction
      approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin
      (standard of care: SOC) for 48 weeks (novel combination treatment: NCT) would
      increase the initial virologic response rate and restore innate and adaptive
      immune responses in CHC. Seven CHC patients with a high viral load and genotype
      1b were treated with NCT. Serum cytokine and chemokine levels were evaluated
      during NCT. NCT prevented viral escape and breakthrough resulting in persistent
      viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in
      both early virologic responders (EAVRs) and late virologic responders (LAVRs);
      CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (P < 0.05) in EAVR
      but not in LAVR during NCT, and IL-12 increased significantly (P < 0.05) and CXCL
      8 decreased significantly (P < 0.05) after the end of NCT in EAVR but not in
      LAVR. NCT prevented viral breakthrough with viral clearance leading to
      improvement of innate and adaptive immunity resulting in a sustained virologic
      response (SVR). NCT (n = 8) achieved a higher SVR rate than SOC (n = 8) in
      difficult-to-treat CHC patients with genotype 1 and high viral loads.

PMID- 22966240
TI  - Gene expression profile reveals abnormalities of multiple signaling pathways in
      mesenchymal stem cell derived from patients with systemic lupus erythematosus.
AB  - We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs) between
      systemic lupus erythematosus (SLE) and normal controls by means of cDNA
      microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our
      results showed there were a total of 1, 905 genes which were differentially
      expressed by BMMSCs derived from SLE patients, of which, 652 genes were
      upregulated and 1, 253 were downregulated. Gene ontology (GO) analysis showed
      that the majority of these genes were related to cell cycle and protein binding.
      Pathway analysis exhibited that differentially regulated signal pathways involved
      actin cytoskeleton, focal adhesion, tight junction, and TGF-beta pathway. The
      high protein level of BMP-5 and low expression of Id-1 indicated that there might
      be dysregulation in BMP/TGF-beta signaling pathway. The expression of Id-1 in SLE
      BMMSCs was reversely correlated with serum TNF-alpha levels. The protein level of
      cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK
      signaling pathway was activated in BMMSCs from SLE patients via phosphorylation
      of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE
      patients was also found disordered. Our results suggested that there were
      distinguished differences of BMMSCs between SLE patients and normal controls.

PMID- 22966242
TI  - Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin
      Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway.
AB  - The healing activity of gallic acid enriched ethanolic extract (GAE) of
      Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric
      ulceration in mice was investigated. The activity was correlated with the ability
      of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology
      of the stomach tissues revealed maximum ulceration on the 3rd day after
      indomethacin (18 mg/kg, single dose) administration that was associated with
      significant increase in inflammatory factors, namely, mucosal myeloperoxidase
      (MPO) activity and inducible nitric oxide synthase (i-NOS) expression.
      Proangiogenic parameters such as the levels of prostaglandin (PG) E(2), vascular
      endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand
      Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin.
      Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to
      effective healing of the acute ulceration, while GAE could reverse the
      indomethacin-induced proinflammatory changes of the designated biochemical
      parameters. The ulcer healing activity of GAE was, however, compromised by
      coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl
      ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine
      hydrochloride (L-NIL). Taken together, these results suggested that the GAE
      treatment accelerates ulcer healing by inducing PGE(2) synthesis and augmenting e
      NOS/i-NOS ratio.

PMID- 22966243
TI  - Microbiological and Pharmacological Evaluation of the Micropropagated Rubus
      liebmannii Medicinal Plant.
AB  - Rubus liebmannii is an endemic species from Mexico used in traditional medicine
      primarily to treat dysentery and cough. The in vitro activity against Giardia
      lamblia and Entamoeba histolytica that produces the ethanolic extract of the
      aerial parts of the plant led us to expand the pharmacological and phytochemical
      research of this species. Gastrointestinal disorders including amebiasis remain
      one of the health problems that need to be addressed and it is of interest to
      find alternatives that improve their treatment. Also, it is important to
      emphasize that R. liebmannii grows wild in the country and is not found in
      abundance; therefore, alternatives that avoid overexploitation of the natural
      resource are mandatory. Ongoing with the evaluation of the potentialities that R.
      liebmannii possesses for treating infectious gastrointestinal diseases, the aim
      of the present study was to evaluate the biological effects and the chemical
      composition of the micropropagated plant.

PMID- 22966241
TI  - The impact of interferon lambda 3 gene polymorphism on natural course and
      treatment of hepatitis C.
AB  - Host genetic factors may predict the outcome and treatment response in hepatitis
      C virus (HCV) infection. Very recently, three landmark genome-wide association
      studies identified single nucleotide polymorphisms near the interleukin 28B
      (IL28B) region which were more frequent in responders to treatment. IL28B encodes
      interferon (IFN)lambda3, a type III IFN involved in host antiviral immunity.
      Favourable variants of the two most widely studied IL28B polymorphisms,
      rs12979860 and rs8099917, are strong pretreatment predictors of early viral
      clearance and sustained viral response in patients with genotype 1 HCV infection.
      Further investigations have implicated IL28B in the development of chronic HCV
      infection versus spontaneous resolution of acute infection and suggest that IL28B
      may be a key factor involved in host immunity against HCV. This paper presents an
      overview about the biological activity and clinical applications of IL28B,
      summarizing the available data on its impact on HCV infection. Moreover, the
      potential usefulness of IFNlambda in the treatment and natural history of this
      disease is also discussed.

PMID- 22966244
TI  - Antioxidant and Anti-Inflammatory Properties of Longan (Dimocarpus longan Lour.)
      Pericarp.
AB  - This study examined the antioxidant and anti-inflammatory activities of the water
      extract of longan pericarp (WLP). The results showed that WLP exhibited radical
      scavenging, reducing activity and liposome protection activity. In addition, WLP
      also inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in
      macrophages. Further, administration of WLP, in the range of 100-400 mg/kg,
      showed a concentration-dependent inhibition on paw edema development following
      carrageenan (Carr) treatment in mice. The anti-inflammatory effects of WLP may be
      related to NO and tumor necrosis factor (TNF-alpha) suppression and associated
      with the increase in the activities of antioxidant enzymes, including catalase,
      superoxide dismutase, and glutathione peroxidase. Overall, the results showed
      that WLP might serve as a natural antioxidant and inflammatory inhibitor.

PMID- 22966245
TI  - Effects of Eurycoma longifolia on Testosterone Level and Bone Structure in an
      Aged Orchidectomised Rat Model.
AB  - Testosterone replacement is the choice of treatment in androgen-deficient
      osteoporosis. However, long-term use of testosterone is potentially carcinogenic.
      Eurycoma longifolia (EL) has been reported to enhance testosterone level and
      prevent bone calcium loss but there is a paucity of research regarding its effect
      on the bone structural parameters. This study was conducted to explore the bone
      structural changes following EL treatment in normal and androgen-deficient
      osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were
      divided into normal control, normal rat supplemented with EL, sham-operated,
      orchidectomised-control, orchidectomised with testosterone replacement, and
      orchidectomised with EL supplementation groups. Testosterone serum was measured
      both before and after the completion of the treatment. After 6 weeks of the
      treatment, the femora were processed for bone histomorphometry. Testosterone
      replacement was able to raise the testosterone level and restore the bone volume
      of orchidectomised rats. EL supplementation failed to emulate both these
      testosterone actions. The inability of EL to do so may be related to the absence
      of testes in the androgen deficient osteoporosis model for EL to stimulate
      testosterone production.

PMID- 22966246
TI  - Longitudinal anti-mullerian hormone in women with polycystic ovary syndrome: an
      acupuncture randomized clinical trial.
AB  - Others have studied acupuncture treatment for polycystic ovary syndrome (PCOS).
      Anti-mullerian hormone (AMH) is positively correlated with the ovarian follicle
      pool, thus making it a useful ovarian reserve measure. AMH is elevated in women
      with PCOS and has been suggested as a diagnostic tool. This study examined the
      impact of electroacupuncture on AMH concentration in women with PCOS. Seventy-one
      women with PCOS participated in a randomized, double-blind, sham-controlled
      clinical trial of acupuncture. Three longitudinal AMH samples over the 5-month
      protocol were compared with objective ovulation parameters primarily using
      nonparametric statistics. Results indicated that AMH levels in PCOS were higher
      than published norms in women without PCOS. There was no difference between the
      true and sham acupuncture arms in the change in AMH longitudinally. Baseline AMH,
      but not the change in AMH over time, was inversely correlated with ovulation and
      menstrual cycle frequencies in both arms combined (P < 0.001). In conclusion, AMH
      correlated with an increased likelihood of monthly ovulation, as expected from
      the literature on women without PCOS. The lack of difference by intervention in
      AMH was consistent with the underlying clinical trial. AMH may be clinically
      useful to predict which PCOS women are more likely to respond to an intervention.

PMID- 22966248
TI  - The use of zoledronic acid in Japanese men with stage D2 prostate cancer.
AB  - Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy
      benefits over pamidronate in preclinical testing. In addition, ZOL is superior to
      pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the
      first bisphosphonate to demonstrate efficacy in patients with bone metastases
      from solid tumors other than breast cancer, such as prostate cancer. In this
      study, we investigated ZOL treatment in 17 Japanese men with advanced prostate
      cancer, treated at the Aichi Medical University Hospital between August 2006 and
      November 2007. The 17 patients had biopsy-confirmed prostate cancer and were
      found to harbor bone metastasis upon bone scintigraphy. ZOL was administered
      intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated
      with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%)
      developed skin rash. No significant side effects were observed. Subjective
      improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is
      a safe and effective drug that remains an important component of the urologist's
      armamentarium against advanced prostate cancer.

PMID- 22966249
TI  - Clinicopathological study of hepatocellular carcinoma with peliotic change.
AB  - Peliosis hepatis-like blood-filled cavities are frequently observed in the tumors
      of hepatocellular carcinoma (HCC). This finding is generally referred to as
      'peliotic change' in HCC. However, the clinicopathological features of HCC with
      peliotic change (PHCC) are not fully understood. These issues are addressed in
      the present study. Among 294 consecutively surgically resected HCCs, the
      clinicopathological features of PHCC were compared with those of a common type of
      HCC (control). PHCC was observed in 116 (39.5%) of 294 HCCs. The mean tumor
      diameter of 3.4+/-0.9 cm of the PHCC group was significantly larger than that of
      the 2.5+/-0.9 cm of the control, and the incidence of PHCC was related to
      increased tumor diameter. In the 116 PHCCs, the tumors were completely or
      incompletely encapsulated. On ultrasonography, PHCCs showed hyperechoic and/or
      mosaic patterns. The mean diameter of 3.5+/-0.8 cm of PHCCs with a hyperechoic
      and/or mosaic pattern was significantly larger than that of 2.3+/-0.9 cm in the
      control. In conclusion, it is necessary for clinicians and pathologists to
      discern the characteristics of peliotic change as a morphological feature that
      modifies ultrasound findings.

PMID- 22966247
TI  - Treatment options in recurrent cervical cancer (Review).
AB  - The management of recurrent cervical cancer depends mainly on previous treatment
      and on the site and extent of recurrence. Concurrent cisplatin-based chemo
      radiation is the treatment of choice for patients with pelvic failure after
      radical hysterectomy alone. However, the safe delivery of high doses of
      radiotherapy is much more difficult in this clinical setting compared with
      primary radiotherapy. Pelvic exenteration usually represents the only therapeutic
      approach with curative intent for women with central pelvic relapse who have
      previously received irradiation. In a recent series, the 5-year overall survival
      and operative mortality after pelvic exenteration ranged from 21 to 61% and from
      1 to 10%, respectively. Free surgical margins, negative lymph nodes, small tumour
      size and long disease-free interval were associated with a more favourable
      prognosis. Currently, pelvic reconstructive procedures (continent urinary
      conduit, low colorectal anastomosis, vaginal reconstruction with myocutaneous
      flaps) are strongly recommended after exenteration. Concurrent cisplatin-based
      chemo-radiation is the treatment of choice for isolated para-aortic lymph node
      failure, with satisfactory chances of a cure in asymptomatic patients.
      Chemotherapy is administered with palliative intent to women with distant or loco
      regional recurrences not amenable by surgery or radiotherapy. Cisplatin is the
      most widely used drug, with a response rate of 17-38% and a median overall
      survival of 6.1-7.1 months. Cisplatin-based combination chemotherapy achieves
      higher response rates (22-68%) when compared with single-agent cisplatin, but
      median overall survival is usually less than one year. In a recent Gynecologic
      Oncology Group (GOG) trial the combination topotecan + cisplatin obtained a
      significantly longer overall survival than single-agent cisplatin in patients
      with metastatic or recurrent or persistent cervical cancer. A subsequent GOG
      study showed a trend in terms of longer overall survival and better quality of
      life for the doublet cisplatin + paclitaxel vs. the doublets cisplatin +
      topotecan, cisplatin + vinorelbine, and cisplatin + gemcitabine. Molecularly
      targeted therapy may represent a novel therapeutic tool, but its use alone or in
      combination with chemotherapy is still investigational.

PMID- 22966250
TI  - Molecular prognostic factors in rectal cancer treated by preoperative
      chemoradiotherapy.
AB  - The present study evaluated the expression of p53, pRb, hMLH1 and MDM2 prior to
      preoperative chemoradiotherapy (CRT) in patients with rectal cancer, and
      attempted to determine any correlation with treatment outcome. Forty-five
      patients with available pretreatment biopsy tissues and who received preoperative
      CRT were enrolled in this study. Preoperative CRT consisted of a median 50.4 Gy
      and 2 cycles of concurrent administration of 5-fluorouracil + leucovorin. Surgery
      was performed approximately seven weeks after CRT. Protein expression in formalin
      fixed paraffin-embedded biopsy specimens was assessed by immunohistochemistry. A
      positive expression of p53, pRb, hMLH1 and MDM2 was found in 40, 46.7, 40 and
      66.7% of the tissue specimens, respectively. The 5-year overall (OS), disease
      free (DFS) and locoregional recurrence-free survival (LRFS) rates for patients
      included in the study were 71.3, 66.1 and 60.9%, respectively. p53 expression
      presented a significantly different OS (positive vs. negative, 45.8 vs. 86.2%;
      p=0.02). However, the expression of pRb, hMLH1 and MDM2 was not significant for
      OS. The expression of p53 was a borderline significant prognostic factor for DFS
      and for LRFS. Age, p53 and MDM2 expression were significant factors in the
      multivariate analysis performed for OS with 12 covariates, including 8
      clinicopathological parameters and 4 proteins. No significant factor affected DFS
      or LRFS in the multivariate analysis. We suggest that the expression of p53 is a
      potential marker of survival. Determinations of this protein expression may be
      useful for selecting candidates from rectal cancer patients for more tailored
      treatment.

PMID- 22966251
TI  - Reduced expression of ASS is closely related to clinicopathological features and
      post-resectional survival of hepatocellular carcinoma.
AB  - Argininosuccinate synthetase (ASS) has previously been proven to be reductively
      expressed in hepatocellular carcinoma (HCC) and various types of HCC cell lines.
      Arginine, the product of ASS, has been used as a target in HCC by recombinant
      human arginase or arginine deiminase, which is now in the phase II clinical trial
      stage. This study aimed to present the levels of ASS expression in HCCs and its
      correlation with clinicopathological features and prognosis of HCC patients.
      Immunohistochemical detection of ASS was performed on samples from 71 patients
      with HCC. Positive staining was found in 21 HCCs, with a score of 2, as well as
      in normal liver tissues. Reduced ASS staining was found in 70.4% (50/71) of HCC
      tissues, including 21 with a score of 0 and 29 with a score of 1. The staining
      score in cancer tissues was significantly associated with gender, background
      liver, histopathological differentiation, recurrence, TNM staging and portal vein
      invasion (P<0.05), but not with age, viral status, tumor size and serum alpha
      fetoprotein level. Patients with a high ASS expression had significantly poorer
      overall and disease-free survival (P<0.001 and P<0.001, respectively). These data
      showed that ASS was reductively or negatively expressed in a large portion of
      HCC, and that ASS levels in HCCs correlated inversely with prognosis. In
      conclusion, a high expression of ASS may be a novel marker of poor prognosis of
      patients presenting with HCC.

PMID- 22966252
TI  - Differential expression of tetraspanin CD9 in basal cell and squamous cell
      carcinomas of the skin and actinic keratosis.
AB  - Tetraspanins are potentially useful molecular markers that differentiate between
      tumour classes and subtypes, since members of this protein family were often
      found to be altered during malignant conversion and tumour progression. In this
      study, we analysed expression of the tetraspanin CD9 in the frequent cutaneous
      neoplasms basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and actinic
      keratosis (AK), which is considered a precursor lesion (carcinoma in situ) from
      which an invasive SCC can develop. A moderate to strong CD9-specific staining of
      the tumour cells' plasma membranes was uniquely observed in all BCCs, SCCs and
      AKs. All SCCs showed additional intracellular CD9 which was rarely (20%) seen in
      AKs. Semi-quantitative assessment of CD9 present in the plasma membranes of
      tumour cells of BCCs (mean staining intensity 1.91) and SCCs (3.64) reflected the
      different CD9 expression of normal precursor cells from which these tumours most
      likely originate. Although considered an intermediate stage in the development of
      SCCs, AKs did not show intense staining of the plasma membranes typical of normal
      keratinocytes or invasive SCCs (p=0.011) but only moderate intensity (mean 1.63).
      In BCCs, significantly (p=0.0005, n=56) stronger CD9-specific immunoreactivity
      was seen in the inner regions of the tumours than at their sites of expansion. In
      summary, our results point to an important role of CD9 at the front of tumour
      expansion in BCCs and SCCs, and in the pathogenesis of invasive SCCs.

PMID- 22966253
TI  - Original and infiltrating patterns of prostatic carcinoma.
AB  - In order to demonstrate the original and infiltrating patterns of prostatic
      carcinoma, the change of histological characteristics associated with increasing
      total cancer volume was investigated. Tissue specimens from 196 histopathological
      cases, obtained at the Kyushu Cancer Center, were reviewed in embedded whole
      mount antegrade radical prostatectomy specimens with adenocarcinoma. Three groups
      (<0.5 cm(3), <=0.5 cm(3) <1 cm(3) and >=1 cm(3)) of total cancer volume were
      identified and a histological study on each group was conducted based on the 2005
      International Society of Urological Pathology Consensus Conference on Gleason
      Grading of Prostatic Carcinoma. With a cancer volume of <0.5 cm(3), Gleason
      primary patterns 3 and 4 were observed in 64.4 and 26.7% of the tumors,
      respectively, while Gleason secondary patterns 3 and 4 were observed in 53.3 and
      42.2%, respectively. The density of the acini was much higher in comparison with
      that of ambient normal acini. The percentage of acini, including cribriform
      carcinoma classified as Gleason pattern 3, increased significantly with the
      increase of cancer volume (p<0.01). The original pattern of the prostatic
      carcinoma was histologically composed of small acini of Gleason patterns 3 and 4
      without forming a cribriform pattern. In addition, prostatic carcinoma
      infiltrated the surrounding stroma at a very early stage, thus infiltrating not
      only the stroma but also the preexisting ducts and acini, causing an increased
      cancer volume.

PMID- 22966254
TI  - Dose-escalation phase I study in metastatic breast cancer patients with
      combination of paclitaxel and tegafur.uracil.
AB  - The study present the results of the dose-setting study of concomitant weekly
      administration of paclitaxel and tegafur.uracil (UFT) for metastatic breast
      cancer. Eligible patients who entered the study underwent two or more courses of
      weekly paclitaxel + UFT therapy as the protocol therapy. The initial dose (level
      1) was paclitaxel, 80 mg/m(2) and UFT, 400 mg/day. At level 2, paclitaxel
      remained the same, but UFT was increased to 600 mg/day. At level 3, only
      paclitaxel was increased to 90 mg/m(2). Twelve patients were enrolled in this
      study between September 2000 and September 2002. Three patients were assigned to
      level 1. Grade 3 liver dysfunction (increased aspartate aminotransferase and
      alanine aminotransferase) was noted in one patient and grade 4 neutropenia was
      noted in one patient, showing that dose-limiting toxicity was detected in 2/3
      patients. In accordance with the protocol, UFT was fixed at 400 mg/day and
      paclitaxel was decreased to 60 mg/m(2) at level -1, and then increased to 70
      mg/m(2) at level 0. The overall effective rate after completion of two courses
      was 33% (3/9) including one case of complete response and two cases of partial
      responses. The remaining patients presented with stable diseases and no patient
      had progressive disease. In this study, weekly paclitaxel with concomitant UFT
      was administered. The recommended doses of paclitaxel and UFT were determined to
      be 70 mg/m(2) and 400 mg/day, respectively. As the toxicity profile shows, the
      highest toxicity level of this regimen was neutropenia and liver dysfunction, and
      dose-limiting toxicity was neutropenia.

PMID- 22966255
TI  - Treatment results including more than third-line chemotherapy for patients with
      advanced non-small cell lung cancer.
AB  - Recently, third-line chemotherapy for advanced non-small cell lung cancer (NSCLC)
      was accepted as a reasonable therapeutic option in patients with a favorable
      performance status. In practice, however, palliative chemotherapy has been
      performed for patients with a favorable performance status, even after third-line
      chemotherapy. Although multiple cycles of palliative chemotherapy were performed
      for these patients, there are little data of observation for courses of treatment
      from first-line to the last chemotherapy. We reviewed the courses of treatment
      for 82 patients with advanced NSCLC that had been admitted for platinum-based
      chemotherapy as a first-line treatment. Additional cycles of palliative
      chemotherapy were provided as monotherapy, based on the attending physician's
      decision considering patient performance status and toxicity after disease
      progression for previous chemotherapy. The median number of chemotherapy lines
      and cycles were 2 and 7, respectively, from first-line to the last chemotherapy.
      The median overall survival was 24 months in the response group of first-line
      chemotherapy, compared to 15 months for the entire study group. In the response
      group, the median number of chemotherapy cycles was 15 and patients received a
      median of 3 lines of chemotherapy. A total of 33 patients were candidate third
      line chemotherapy or more. The median survival was 23 months for patients treated
      with more than third-line chemotherapy, compared to 7 months for patients treated
      with less than second-line chemotherapy. We conclude that long-standing
      chemotherapy is not beneficial to all NSCLC patients. However, patients with a
      favorable response to first-line chemotherapy tend to receive a higher number and
      more cycles of chemotherapy than the non-response group. Furthermore, multi-line
      chemotherapy appears to increase survival in the response group. Further studies
      will be needed to confirm these results.

PMID- 22966256
TI  - Clinical translation in the treatment of hepatocellular carcinoma following the
      introduction of contrast-enhanced ultrasonography with Sonazoid.
AB  - Some hepatocellular carcinoma (HCC) nodules are detectable with dynamic computed
      tomography, but not by conventional B-mode ultrasonography (US). Contrast
      enhanced US (CEUS) with Sonazoid, a new injectable contrast agent, has been used
      in Japan since January 2007. The primary advantage of this agent is the ability
      to maintain observations continuously in the Kupffer phase. We assessed the
      clinical role of CEUS with Sonazoid for radiofrequency ablation (RFA). From
      January 2005 to December 2008, 1142 patients were treated with surgical
      resection, RFA, percutaneous ethanol injection or transcatheter arterial
      chemoembolization, following the exclusion of those patients treated with
      chemotherapy or supportive care. The patients included in the study were divided
      into the pre-CEUS (n=451, 2005 and 2006) and post-CEUS (n=691, 2007 and 2008)
      groups. Clinical background (e.g., etiology, Child-Pugh classification, tumor
      node metastasis stage, percentage of patients matched with Milan criteria and
      selected therapies) was compared between the two groups. In addition, naive cases
      were compared between the groups. There were 130 naive HCC cases in the pre-CEUS
      group and 171 in the post-CEUS group. Although there were no significant
      differences for clinical background, the percentage of RFA cases increased from
      21 (n=95) to 32% (n=219) and from 32 (n=41) to 52% (n=89) for total and naive
      subjects, respectively, after CEUS was introduced (P<0.01). In naive cases
      treated with RFA, tumor numbers in the post-CEUS group were larger than those of
      the pre-CEUS group (1.15+/-0.48 vs. 1.40+/-0.67; P<0.01). CEUS with Sonazoid,
      therefore, makes it possible to perform RFA in a considerable number of HCC cases
      that would otherwise be invisible by conventional B-mode US.

PMID- 22966257
TI  - A water-soluble extract from cultured medium of Ganoderma lucidum (Reishi)
      mycelia attenuates the small intestinal injury induced by anti-cancer drugs.
AB  - The present study investigated whether a water-soluble extract from the culture
      medium of Ganoderma lucidum (Reishi) mycelia (MAK) is able to protect the small
      intestine against damage induced by anti-cancer drugs. Six-week-old male
      B6C3F1/Crlj mice were fed a basal diet (MF) alone or with various doses of MAK or
      Agarics blazei Murrill (AGA) beginning one week before treatment with the anti
      cancer drugs. Mice were sacrificed 3.5 days after injection of the anti-cancer
      drug, the small intestine was removed and tissue specimens were examined for the
      regeneration of small intestinal crypts. In experiment 1, the number of
      regenerative crypts after the administration of 5-fluorouracil (5FU)
      intravenously (250 mg/kg) or intraperitoneally (250 or 500 mg/kg) was compared
      after treatment with MAK or AGA. MAK protected against 5FU-induced small
      intestinal injury whereas AGA did not. In experiment 2, we investigated the
      protective effect of MAK against small intestinal injury induced by the anti
      cancer drugs: UFT (tegafur with uracil; 1,000 mg/kg, orally), cisplatin (CDDP;
      12.5 and 25 mg/kg, intraperitoneally), cyclophosphamide (CPA; 250 mg/kg, orally)
      and gefitinib (Iressa; 2,000 and 4,000 mg/kg, orally). UFT and CDDP decreased the
      number of regenerative crypts, but treatment with MAK attenuated the extent of
      UFT- or CDDP-induced small intestinal injury. CPA or Iressa plus MAK up-regulated
      crypt regeneration. The present results indicate that MAK ameliorates the small
      intestinal injury caused by several anti-cancer drugs, suggesting that MAK is a
      potential preventive agent against this common adverse effect of chemotherapy.

PMID- 22966258
TI  - In vivo anti-tumor activity of photodynamic therapy with intravenous
      administration of acridine orange, followed by illumination with high-power flash
      wave light in a mouse osteosarcoma model.
AB  - In a recent study, we demonstrated that a high-power flash wave light (FWL) from
      a xenon lamp exerted a stronger cytocidal effect against a mouse osteosarcoma
      cell line than continuous wave light (CWL) in photodynamic therapy with acridine
      orange (AO-PDT). Based on our in vitro results, we investigated the in vivo anti
      tumor activity of AO-PDT using flash wave light from a xenon lamp in a mouse
      osteosarcoma model. Mouse osteosarcoma cells (LM8) were injected into the
      subcutaneous tissue of the back of C3H mice, and tumors that grew to
      approximately 3 mm in diameter were treated by AO-PDT using FWL. AO was
      administered by intravenous injection and 2 h later the entire body of the mouse
      was illuminated with FWL from a xenon lamp. Significant growth inhibition of the
      tumor xenografts was observed as compared with that in the control group,
      suggesting that AO-PDT with FWL may be useful in the treatment of osteosarcoma.
      An immunohistochemical study of the tumors treated by AO-PDT showed that the
      underlying mechanism of the tumor growth inhibition involved both apoptosis and
      necrosis. In conclusion, it appears that following the intravenous administration
      of AO, AO-PDT in combination with FWL exerts strong anti-tumor activity.
      Inhibitory effects against growth of the primary tumor in human patients with
      osteosarcoma as well as other musculoskeletal sarcomas were also observed.

PMID- 22966259
TI  - Oral low-dose dexamethasone for androgen-independent prostate cancer patients.
AB  - We retrospectively evaluated the outcome of oral low-dose dexamethasone (DXM)
      therapy for androgen-independent prostate cancer (AIPC). Between January 1999 and
      April 2006, 99 consecutive patients with AIPC were enrolled in this study. The
      median patient age was 70 years (range 46-86), and the median pretreatment
      prostate-specific antigen (PSA) level was 243 ng/ml (range 8.2-29600). Median
      follow-up was 41.9 months (range 11.4-170.4). Upon biochemical failure, patients
      were treated with oral low-dose DXM. A total of 40 of the 99 cases (40.4%) showed
      a >=50% decrease in serum PSA levels (PSA responders). Twenty-five cases (25.2%)
      showed a <50% decrease in PSA, and the remaining 34 cases (34.3%) had increased
      PSA levels (PSA non-responders). The median PSA progression-free survival was 3.0
      (range 0-27) and 8.0 months (range 2-27) for the entire cohort and PSA
      responders, respectively. The PSA responders had a significantly increased
      survival (median 30.1 months) compared to the non-responders (median 8.8 months,
      P<0.001). Of the 34 patients who were under pain control for bone metastases
      before the administration of DXM, 23 (67.6%) were able to discontinue the regular
      use of analgesics. The PSA responders also showed an increase in hemoglobin
      levels. The change in serum interleukin-6 levels was significantly associated
      with a response to DXM (P=0.0065). Severe adverse events of DXM were rare.
      Clinicopathological factors predicting the PSA response to DXM were age, time
      from initial androgen deprivation therapy to DXM and PSA velocity prior to DXM.
      In conclusion, oral low-dose DXM led to an acceptable PSA response in patients
      with AIPC. Thus, this therapy may be an effective and safe alternative for the
      treatment of AIPC, particularly for patients who are not favourable candidates
      for chemotherapy.

PMID- 22966260
TI  - Multicentre phase II study of leucovorin plus pharmacokinetic modulating
      chemotherapy for metastatic colorectal cancer.
AB  - The optimal administration of 5-fluorouracil (5-FU)/leucovorin (LV) for
      colorectal cancer (CRC) has yet to be fully defined although evidence of the
      combination has already been established. In a multicentre phase II study,
      pharmacokinetic modulating chemotherapy (PMC), which is based on the concept that
      continuous intravenous 5-FU infusion can be enhanced by low-dose oral
      uracil/tegafur, was combined with LV and administered. Thirty-seven patients were
      enrolled. The objective response rate was 31.4% and the tumour stabilization rate
      was 85.7%. The most common toxic effects were neutropenia and hand-foot skin
      reactions although no life-threatening grade 3-4 toxicities were noted. Grade 3
      toxicities such as neutropenia, nausea, diarrhoea and oesophagitis occurred in
      one patient each. We identified the usefulness of a new type of infusional 5-FU
      combined with LV for the treatment of CRC. The combination of PMC and LV is
      active with an acceptable rate of toxicity as a first-line treatment of advanced
      CRC.

PMID- 22966261
TI  - Renal carcinoid tumor: An immunohistochemical and molecular genetic study of four
      cases.
AB  - Few genetic studies of renal carcinoid tumor have been conducted thus far. We
      performed immunohistochemical and genetic examinations on four renal carcinoid
      tumors. Histologically, the tumors consisted of neoplastic cells with round to
      oval nuclei. Various growth patterns such as tightly packed cords and trabeculae,
      ribbon-like, trabecular, sheet-like or solid growth were observed. Nuclear
      chromatin showed a coarse and granular pattern. Immunohistochemically, tumors
      were positive for chromogranin A and synaptophysin. In the fluorescence in situ
      hybridization study, three of four tumors revealed monosomy of chromosome 3
      (D3Z1), but one tumor showed monosomy of chromosome 13 (D13S319/13q34). Using PCR
      amplification and fragment analysis of three microsatellite markers (D3S1300,
      D3S666 and D3S1768) of chromosome arm 3p, one tumor showed loss of heterozygosity
      at D3S1300 and D3S1768, one tumor was not informative and the analysis of two
      tumors failed due to low DNA quality. In three cases, the VHL gene status was
      tested. Two tumors showed wild-type, but the analysis of one tumor failed to
      provide adequate results. In conclusion, we suggest that the abnormality of
      chromosome 3 is involved in the pathogenesis of renal carcinoid tumor.

PMID- 22966262
TI  - Radiofrequency ablation induces dedifferentiation of hepatocellular carcinoma.
AB  - Radiofrequency ablation (RFA) has been reported to be a minimally invasive and
      effective procedure for the treatment of hepatocellular carcinoma (HCC). However,
      the pattern of recurrence and complications following RFA have yet to be fully
      identified. During the period January 2000 to December 2006, we performed HCC
      resections in 15 patients who developed local recurrence after RFA, as well as in
      144 patients without RFA. In patients with local recurrence of HCC after RFA, the
      tumors showed a more invasive growth, more vascular invasion and less
      differentiation compared with tumors of patients without RFA. In 6 of the 15
      patients with recurrence after RFA, needle biopsy of the HCC was performed before
      tumor ablation. In five of these 6 patients, dedifferentiation of the tumor was
      observed. These findings suggest that heat shock due to RFA induces
      dedifferentiation of HCC. Recurrence after RFA may result in an aggressive tumor
      that precludes any possibility of cure. RFA must not be considered a suitable
      alternative to surgery in patients with a low surgical risk. Instead, RFA should
      be performed according to strict indications by skilled operators using the
      latest devices.

PMID- 22966263
TI  - Phase I trial of oxaliplatin plus S-1 chemotherapy in patients with metastatic
      colorectal cancer.
AB  - Advanced colorectal cancer can be effectively treated with S-1, as well as with a
      combination of oxaliplatin, 5-fluorouracil (5FU) and leucovorin (LV). However, S
      1 together with oxaliplatin may provide a more convenient alternative to 5FU/LV.
      To evaluate the performance of S-1 combined with oxaliplatin for patients with
      colorectal cancer, we conducted a Phase I clinical trial in an outpatient
      setting. We administered S-1 to 15 patients with advanced colorectal
      adenocarcinoma for two weeks followed by one week of rest. Oxaliplatin was also
      administered on day 1 of the S-1 cycle. The dose of oxaliplatin was increased
      from 40 to 85 mg/m(2) to define the maximum tolerated dose and recommended dose
      in preparation for a Phase II trial. We administered 102 courses of treatment to
      15 patients. Grade 3 thrombocytopenia developed in only 1 patient at a dose of 85
      mg/m(2) of oxaliplatin plus oral S-1. No other grade 3-4 toxicities developed. No
      dose-limiting toxicity developed at level 4 of our regimen (oxaliplatin 85
      mg/m(2)), and the recommended dose for a Phase II trial was 85 mg/m(2) of
      oxaliplatin in an outpatient setting.

PMID- 22966264
TI  - Sentinel lymph node biopsy in breast cancer patients undergoing skin/nipple
      sparing mastectomy and immediate autologous reconstruction.
AB  - Immediate breast reconstruction following mastectomy is an effective treatment
      for breast cancer patients. Among several implant options, a latissimus dorsi
      myocutaneous (LDM) flap is used mainly due to the ease and minimal invasiveness
      of the procedure. The role of sentinel lymph node (SLN) biopsy with total
      mastectomy is evolving. Since SLN biopsy is not included in health insurance
      coverage in the treatment of patients in Japan, it is not generally performed as
      a separate procedure due to its cost. The present study reviewed the results of
      seven patients who underwent initial-staged SLN biopsy followed by planned
      mastectomy and LDM flap reconstruction. Two patients with positive SLNs showed
      macrometastases and underwent modified radical mastectomy with immediate
      reconstruction. In contrast, cases showing negative results for sentinel lymph
      nodes underwent total mastectomy. There were no false-negative cases among the
      SLN biopsy-negative cases. When an SLN is found to be positive on final
      pathology, the patient with reconstruction by LDM flap generally requires a
      potentially difficult reoperation on the remaining axillary nodes. When initial
      SLN biopsy is generally performed as a separate procedure in Japan, it will be an
      effective method for screening the axilla for patients who wish to undergo LDM
      flap reconstruction.

PMID- 22966265
TI  - Overexpression of neutrophil gelatinase-associated lipocalin and its receptor in
      colorectal carcinoma: Significant correlation with cell differentiation and
      tumour invasion.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin
      family, is related to imflammation and tumour. Recently, a specific cell-surface
      receptor (24p3R/NGALR) for lipocalin 24p3 was reported. However, the
      characteristics of NGALR expression in colorectal carcinoma (CRC) are not known.
      The objectives of this study were to investigate the expression of NGAL and NGALR
      in CRC specimens, and determine any relationship between the expression of these
      proteins and tumour progression. In the present study, CRC specimens of 102
      patients were obtained, and the expression of NGAL, NGALR, ferritin and Ki67 was
      analyzed in paraffin sections by immunohistochemistry. Statistical analyses of
      the data collected were performed with SPSS software. We found that the
      cytoplasmic staining of NGAL, NGALR and ferritin, as well as the nuclear staining
      of Ki67 were significantly up-regulated in CRC tissues compared with normal
      colorectal tissues. Expression of NGAL was related to the deeper invasion of CRC
      (P=0.026), while NGALR was significantly associated with a deeper invasion
      (P=0.018) and a high degree of Tumor, Node and Metastasis stages (P=0.042) in
      CRC. The NGAL/NGALR co-expression was associated with poor cellular
      differentiation (P=0.004). Positive correlations between NGAL and NGALR (r=0.432,
      P<0.01), NGAL and ferritin (r=0.374, P<0.001), NGALR and Ki67 (r=0.228, P<0.05),
      NGAL/NGALR co-expression and ferritin (r=0.349, P<0.001), as well as NGAL/NGALR
      co-expression and Ki67 (r=0.205, P<0.05) were observed. However, the expression
      of NGAL or NGALR was not significantly associated with patient survival. These
      findings detected an elevated expression of NGAL and NGALR resulting in poor
      cellular differentiation and a deeper invasion of CRC. Thus, NGALR may be a novel
      target for the treatment of CRC.

PMID- 22966266
TI  - Arylthioindoles: Promising compounds against cancer cell proliferation.
AB  - Drugs that are able to modulate the microtubule dynamics either by inhibiting
      tubulin polymerization or by blocking microtubule disassembly are of great
      interest in anti-cancer therapy; a number of them are currently applied in
      clinical development. Tubulin polymerization inhibitors, including
      arylthioindoles, are characterized by the presence of an indole nucleus and have
      been obtained from natural sources or prepared by semi-synthesis. We
      characterized the effect of 5-bromo-3-[(3,4,5-trimetoxyphenyl)thio]-1H-indole (RS
      2518) on the metabolism of human cell lines derived from solid tumors. We found
      that this new compound impairs cell adhesion, arrests the cells in the G(2)/M
      cell cycle phase and inhibits cell proliferation, thus leading to apoptosis. The
      described effects of RS 2518 on cancer cells have led to its selection as a lead
      compound for further studies. Some analogues have been developed and tested on a
      panel of cancer cell lines.

PMID- 22966267
TI  - Induction of the differentiation of cultured endometrial carcinoma cells by type
      I collagen: Relevance of sulfolipids.
AB  - This study aimed to promote gland formation in cells derived from endometrial
      cancer, and assess the relevance of sulfolipids by performing culture with type I
      collagen. Tumors were developed in nude mice using cultured cell lines, gland
      formation was induced by culture with type I collagen and the composition of
      tumor cell sulfolipids was analyzed. Results showed that after culturing the
      cells on type I collagen gel, the gel was floated. Another layer of gel was
      placed on top so that the cells were sandwiched between two layers. Using this
      method, it was possible to induce gland formation in cells that formed only
      poorly differentiated tumors in nude mice. Mucous staining and electron
      microscopy demonstrated polarity of the glands. The cell lines that showed gland
      formation expressed sulfolipids, but not cholesterol sulfate. In conclusion, type
      I collagen and sulfolipids are involved in the process of gland formation in
      endometrioid adenocarcinoma.

PMID- 22966268
TI  - Postoperative infections are associated with adverse outcome after resection with
      curative intent for colorectal cancer.
AB  - This study focused on the impact of post-operative infection on patient outcome
      after resection with curative intent for colorectal cancer. Postoperative
      surgical and medical complications have been implicated as a negative predictor
      of long-term outcome in various malignancies. We studied a population of 1083
      patients who underwent resection with curative intent for colorectal cancer.
      These patients were divided into 2 groups based on the occurrence (65 patients,
      6%) or absence (1018 patients, 94%) of postoperative complications due to
      infection. We investigated the demographic and clinicopathological features of
      each patient with and without postoperative infectious complications, as well as
      the impact of postoperative infection on long-term survival. Results showed that
      patients with postoperative infectious complications had diabetes mellitus more
      frequently and also had urgent surgery compared to those without infectious
      complications. In addition, patients with postoperative infectious complications
      had a significantly more unfavorable outcome compared with those without
      postoperative infection in cancer-specific, but not overall survival.
      Multivariate analysis demonstrated that age, rectal cancer and tumor stage
      correlated with overall survival, but not postoperative infectious complications.
      However, postoperative infections, as well as gender, were associated with the
      length of time until the patient succumbed from the recurrence of colorectal
      cancer after resection for curative intent. Thus, postoperative infectious
      complications are predictors of adverse clinical outcome in patients with
      colorectal cancer. However, further immunological study is necessary to confirm
      the biological significance of these findings.

PMID- 22966269
TI  - T regulatory cell markers in oral squamous cell carcinoma: Relationship with
      survival and tumor aggressiveness.
AB  - Tumor-infiltrating lymphocytes (TILs) are a heterogeneous cell family which plays
      an important role in tumor-associated immune response. Of these, T regulatory
      (Treg) cells have also been shown to inhibit anti-tumor response. We aimed to
      evaluate the expression of T regulatory cell markers (CD4, CD25, CTLA-4 and
      FoxP3) in samples of oral cavity squamous cell carcinoma (OCSCC) and lip SCC
      (LSCC) by immunohistochemistry. The relationship of Treg markers with survival
      data and the proliferative index were also evaluated. We observed similar numbers
      of CD4-, CD25- and FoxP3(+) cells in OCSCC and LSCC. On the other hand, numbers
      of CTLA-4(+) cells were significantly lower in OCSCC than in LSCC. OCSCC samples
      with high numbers of CD4 exhibited a high proliferative index, while samples with
      high CTLA-4 counts demonstrated a low tumoral proliferative index. A log-rank
      test showed that patients with OCSCC that presented high counts of CD4 showed a
      significantly decreased survival compared with patients with low cell counts. In
      contrast, high CD25(+) cell counts were associated with increased survival. Our
      results suggest an association of CD4 with poor prognosis, while CD25 expression
      is related with favorable prognosis. These findings result from the heterogeneity
      of TIL subsets that display an antagonistic role in tumor immune cell response.

PMID- 22966270
TI  - Combined use of free vascularised fibula graft and extracorporeally irradiated
      osteochondral graft for osteosarcoma of the proximal ulna.
AB  - The elbow is an uncommon site for malignant bone tumors. Surgical options for the
      reconstruction of the elbow joint are limited and technically challenging. In
      this study, we describe a patient with osteosarcoma of the proximal ulna treated
      by wide resection and reconstruction with a combined use of free vascularised
      fibula graft and extracorporeally irradiated osteochondral graft. Ten years after
      the surgery, the patient is alive, without disease and is able to play golf with
      no lateral instability or pain of the elbow joint. A vascularised fibula,
      combined with extracorporeally irradiated osteochondral graft with ligamentous
      repair is one of the options for the treatment of malignant bone tumor of the
      proximal ulna.

PMID- 22966271
TI  - Tumorigenesis of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), but not
      enhancing effects of concomitant high-fat diet, on lung carcinogenesis in female
      A/J mice.
AB  - It has been reported that 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)
      induces liver tumors and to a lesser extent lung lesions, lymphomas and leukemias
      in CDF(1) mice. Since a number of case control studies have pointed to a positive
      association between fat consumption and lung cancer, we examined the lung
      carcinogenic potential of MeIQx treatment concomitant with a high-fat diet using
      female A/J mice. Groups 1 and 2 were fed a diet supplemented with MeIQx at a
      concentration of 600 ppm. Groups 1 and 3 received a diet containing 20% corn oil
      and group 4 was fed the basal diet alone. After 1 week, 10 mice in each group
      were sacrificed for measurement of cytochrome P450 (CYP)1A2 mRNA in the liver and
      lung. The remaining mice were maintained on their respective diets until
      termination, 32 weeks after the initial MeIQx treatment, when lung proliferative
      lesions were analyzed. The incidences and multiplicities of hyperplasias and
      adenomas in MeIQx-treated groups (groups 1 and 2) were significantly higher than
      in the groups without MeIQx treatment, with a significant increase in the
      incidences and multiplicities of adenomas + carcinomas, as well as hyperplasia +
      adenomas + carcinomas (lung proliferative lesions). Lung carcinomas were observed
      in 1 mouse in each of the MeIQx-treated groups. However, the high-fat diet
      (groups 1 and 3) did not affect the incidences or multiplicities of lung
      proliferative lesions. Expression levels of CYP1A2 mRNA after MeIQx treatment
      significantly increased >3-fold in livers, but no significant change was noted in
      the lungs, where levels were very low at 1/210 and 1/923 the values for livers.
      In conclusion, following a 32-week period, we confirmed the lung tumorigenic
      potential of MeIQx which possibly occurs due to proximate carcinogens activated
      by CYP1A2 in the liver. However, we failed to detect any influence of a high-fat
      diet.

PMID- 22966272
TI  - DNA methyltransferase expression in odontogenic cysts and tumours.
AB  - Epigenetic silencing of gene expression by promoter CpG island hypermethylation
      is promoted by the enzymes, DNA methyltransferases (DNMTs). DNMT3a is mainly
      involved in de novo methylation, whereas DNMT1 acts mainly as a maintenance
      methyltransferase. The purpose of this study was to investigate the
      immunoexpression of DNMT1 and DNMT3a in a set of odontogenic cysts and tumours.
      Formalin-fixed and paraffin-embedded tissue samples of eight radicular cysts, 10
      odontogenic keratocysts (OKC), eight adenomatoid odontogenic tumours (AOT), 16
      ameloblastomas and eight samples of normal mucosae were included in the study.
      The DNMT1 and DNMT3a proteins were identified by using a highly sensitive polymer
      based system. We found that the normal oral mucosa, OKC, AOT, radicular cyst and
      ameloblastomas samples showed a widespread nuclear and cytoplasmic
      immunopositivity for DNMT1. Some radicular cysts, ameloblastomas, AOT and OKC
      samples presented a positive cytoplasmic reaction for DNMT3a, while negative
      staining was observed in the normal oral mucosa. Nuclear positivity was found
      only in the suprabasal cell layers of three OKC samples. Our study shows an
      increased expression of DNMT3a in odontogenic cysts and tumours, confirming that
      epigenetic mechanisms are involved in the development of these tumours.

PMID- 22966273
TI  - Efficacy of S-1 monotherapy for non-small cell lung cancer after the failure of
      two or more prior chemotherapy regimens.
AB  - The efficacy and safety of S-1 monotherapy for patients with advanced or
      recurrent non-small cell lung cancer (NSCLC) after the failure of two or more
      prior chemotherapy regimens were investigated. Records of 36 patients with
      advanced or recurrent NSCLC who received S-1 monotherapy between January 2005 and
      December 2008, following the failure of previous chemotherapy, were reviewed
      retrospectively at two institutions. S-1 was given orally twice daily on days 1
      28 every six weeks; the dose was based on body surface area. The median number of
      prior chemotherapy regimens was three (range 2-5), and that of courses given per
      patient was two (range 1-10). No patient achieved complete response, 4 patients
      (11.1%) achieved partial response, 10 patients (27%) had stable disease and 18
      patients (50%) had progressive disease. The median progression-free survival was
      3 months and the median overall survival was 15.2 months. No grade 4
      hematological toxicity was noted. Grade >=3 non-hematological toxicities were
      observed in 5 patients (13.9%). No deaths related to S-1 monotherapy occurred. S
      1 monotherapy exhibits activity with acceptable toxicity as third-line or
      subsequent chemotherapy for advanced NSCLC.

PMID- 22966274
TI  - The ABCB1 3435 T allele does not increase the risk of paclitaxel-induced
      neurotoxicity.
AB  - Paclitaxel is a frequently used anticancer drug with considerable inter
      individual variability in terms of drug efficiency and toxicity. The reasons for
      this variability have not been fully explained. The purpose of this study was to
      evaluate the possible relationship between paclitaxel-induced neurotoxicity and
      the distribution of genetic variations with reported functional significance in
      the ABCB1, CYP2C8 and CYP3A4 genes that are all implicated in taxol metabolism.
      Women (n=36) experiencing paclitaxel-induced neurotoxicity were included in the
      study, and the ABCB1 G2677A/T and C3435T as well as CYP2C8(*)3 and CYP3A4(*)1b
      allele frequencies were determined using PCR-RFLP and DNA sequence analysis. We
      showed that the ABCB1 3435T allele, previously reported as a risk allele for
      neurotoxicity, did not correlate with the occurrence of neurotoxicity in our
      patient sample (Chi-square test, p=0.61). Furthermore, we showed that neither the
      CYP2C8(*)3 nor CYP3A4(*)1b alleles, that both lead to diminished enzyme activity,
      correlated with paclitaxel-induced neurotoxicity. The occurrence and variation in
      severity of neurotoxicity in our Swedish patient sample could therefore not be
      explained by the reported functional polymorphisms in the ABCB1, CYP2C8 and
      CYP3A4 genes.

PMID- 22966275
TI  - Diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography for
      pancreatic neuroendocrine tumors with reference to the World Health Organization
      classification.
AB  - The 2004 classification of the World Health Organization (WHO) has demonstrated
      an efficacy for prediction of the prognosis of pancreatic neuroendocrine tumors.
      This study aimed to assess the predictive value of preoperative (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in relation to the 2004
      WHO criteria. The histology of 21 pancreatic endocrine tumors resected at our
      hospital was reviewed and the tumors were classified according to the 2004 WHO
      criteria. FDG-PET findings were analyzed by comparing the findings with CT scans.
      FDG uptake was positive in 10 primary endocrine tumors (47%), but no uptake was
      seen in 11 tumors. In relation to the 2004 WHO classification, 1 out of 8 well
      differentiated tumors with benign behavior was positive by PET (12.5%), 4 out of
      7 well-differentiated tumors with uncertain behavior were positive (57%) and 4
      low-grade malignant tumors were positive (100%). According to the WHO criteria,
      the rate of positive FDG uptake increased as the malignant potential increased.
      The metastases of low-grade malignant tumors also showed a positive FDG uptake.
      In conclusion, from our limited experience, FDG-PET appears to be useful for
      identifying pancreatic neuroendocrine tumors with a higher malignant potential.
      In addition, FDG-PET can detect distant metastases and may contribute to better
      staging of advanced disease.

PMID- 22966276
TI  - Changes in bowel mucosal permeability and wound healing after neoadjuvant
      chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is
      a promising approach for locally advanced gastric cancer. We investigated the
      influence of NAC with 5-FU/CDDP on the permeability of intestinal mucosa and
      wound healing. Male Sprague Dawley rats were divided into four groups (n=6).
      Group 1 received saline (control group) and Groups 2-4 were administered
      preoperative 5-FU/CDDP (NAC groups). The NAC consisted of daily intraperitoneal
      administration of 5-FU from day 1 to 5 and from day 8 to 12 and intravenous
      administration of CDDP on days 2 and 9. The rats underwent gastrotomy (1.0 cm)
      with a laparotomy of 3 cm in length, under general anesthesia. Seven days after
      surgery, the rats were orally administered with phenolsulfonphthalein (PSP), and
      the 24-h urinary excretion of PSP was quantified. On postoperative day 8, the
      bursting pressure (BP) of the gastric suture line and the tensile strength of the
      abdominal wound were measured. The hydroxyproline (HP) content in the tissue of
      the abdominal suture line was then measured, and the number of fibroblast cells
      in the tissue of the gastric suture line was calculated by histopathological
      examination. The PSP urinary excretion rate was significantly higher in Group 2
      in comparison with the other groups (P<0.05), while the BP of a selected
      gastrorrhaphy region was significantly lower in Group 2 (P<0.05). No significant
      differences were noted in the HP content. NAC with 5-FU/CDDP disturbs the healing
      of intestinal anastomoses when the interval between chemotherapy and surgery is
      insufficient. Neither HP content nor fibroblast counts were correlated with BP.
      Consequently, NAC appeared to affect the remodeling of collagen fiber. Thus, the
      integrity of the intestine may play a role in intestinal wound healing.

PMID- 22966277
TI  - Effects of chronic vs. intermittent calorie restriction on mammary tumor
      incidence and serum adiponectin and leptin levels in MMTV-TGF-alpha mice at
      different ages.
AB  - Calorie restriction prevents mammary tumor (MT) development in rodents. Usually,
      chronic calorie restriction (CCR) has been implemented. In contrast, intermittent
      calorie restriction (ICR) has been less frequently used. Recent studies indicate
      that when a direct comparison of the same degree of CCR vs. ICR was made using
      MMTV-TGF-alpha mice which develop MTs in the second year of life, ICR provided
      greater protection than CCR in delaying MT detection and reducing tumor
      incidence. Adiponectin and leptin are two adipocytokines secreted from adipose
      tissue which have opposite effects on many physiological functions, including
      proliferation of human breast cancer cells. A recent study indicated that a low
      adiponectin/leptin ratio was associated with breast cancer. We evaluated the
      relationship of adiponectin and leptin to MT development in MMTV-TGF-alpha
      calorie-restricted mice at several ages. Mice were enrolled at 10 weeks of age
      and subjected to 25% caloric reduction implemented either chronically or
      intermittently. Mice were euthanized at designated time points up to 74 weeks of
      age. Serum samples were collected to measure adiponectin and leptin
      concentrations. Both CCR and ICR mice had significantly reduced MT incidence. For
      the groups studied, serum leptin increased over time, while there was a trend for
      an increase in serum adiponectin levels in ad libitum and ICR mice, with no
      change in CCR mice between 10 and 74 weeks of age. The adiponectin/leptin ratio
      was significantly reduced as mice aged, but this ratio in ICR mice was
      significantly higher than that for ad libitum and CCR mice. No correlation was
      noted between serum adiponectin and leptin. These findings demonstrate that
      intermittent calorie restriction delays the early development of MTs. This delay
      was associated with reduced serum leptin levels following the restriction phases
      of the protocol. Additionally, serum leptin levels correlated with body weight
      and body fat in the groups studied.

PMID- 22966278
TI  - Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene
      delivery to cancer cells.
AB  - Peritoneal dissemination of cancer cells is characteristic of advanced stages of
      ovarian, breast and lung cancers, and is associated with poor patient survival.
      The presence of cancer cells in effusions complicates treatment protocols, while
      cell eradication is seriously limited. One of the novel options available is
      cancer gene therapy with recombinant adeno-associated viruses. This combination
      represents the most promising gene delivery vehicles to neoplasmatic cells within
      serosal cavities due to their unique properties that include the ability to
      infect proliferating cells of broad host range, as well as the potential of long
      term expression. Recombinant infectious adeno-associated virus serotype 2
      particles (rAAV2) were produced in a helper-free system using an AAV-293
      packaging cell line, and quantitatively analyzed by real-time PCR. Balb/c mice
      intraperitoneally pre-injected with L1 cancer cells were treated with different
      doses of rAAV2. Subsequently, the mice were sacrificed and intraperitoneal
      effusions were analyzed for rAAV presence and rAAV/beta-galactosidase (LacZ)
      vector efficiency in order to infect cancer cells within the peritoneal cavity.
      We reported an efficient infection of L1 cancer cells disseminated into the
      peritoneal cavity by rAAV2. The expression of reporter genes (GFP and LacZ)
      attributable to the rAAV cell uptake was closely dependent on an applied
      multiplicity of infection ratio (MOI). The highest infection efficiency was
      observed at a MOI of 50 and 200. Our study confirmed the ability of adeno
      associated viruses to facilitate gene transferability to cancer cells
      disseminated in the serosal cavity, as well as the potential usefulness of these
      viruses as a new approach in cancer gene therapy.

PMID- 22966279
TI  - Impact of MAGE-A antigens on taxane response in oral squamous cell carcinoma.
AB  - MAGE-A antigens are a subgroup of cancer/testis antigens that are exclusively
      expressed in malignant cells. Only scarce information on the function of MAGE-A
      antigens is available. There is some evidence that they may influence the
      response to chemotherapeutic drugs. This study aimed to evaluate the impact of
      the MAGE-A antigen subgroups MAGE-A2, -A3, -A4 and -A6 on oral squamous cell
      carcinoma cell lines treated with docetaxel and paclitaxel. Five oral squamous
      cell carcinoma cell lines were characterized for their quantitative expression of
      MAGE-A2, -A3, -A4 and -A6. The cell lines were treated with concentrations
      ranging from 0.025 to 0.8 MUM of docetaxel and paclitaxel. The amount of viable
      cells after 24 and 48 h was measured. The measurements were statistically
      correlated with MAGE-A expression. All cell lines responded to docetaxel and
      paclitaxel. One cell line showed a statistically significant weaker response to
      the taxane treatment. This cell line was the only one that expressed MAGE-A4.
      MAGE-A4 has a statistically significant impact on the tumour response to
      docetaxel and paclitaxel in oral squamous cell carcinoma. This may influence
      treatment options and the course of the disease. Therefore, patients should be
      evaluated for MAGE-A4 expression before treatment with taxanes.

PMID- 22966280
TI  - The Mantle Cell Lymphoma International Prognostic Index: Does it work in routine
      practice?
AB  - The Mantle Cell Lymphoma International Prognostic Index (MIPI) combines four
      factors to differentiate low-, intermediate- and high-risk prognostic groups in
      advanced mantle cell lymphoma using data from patients treated in clinical
      trials. To evaluate its use in routine practice, we applied the simplified index
      retrospectively to 50 consecutive new patients attending our lymphoma service. In
      the log-rank and multiple comparison statistical tests there was favorable
      differentiation between survival curves, and particularly between the high- and
      low-risk groups. We concluded that the MIPI is of value in routine lymphoma
      practice.

PMID- 22966281
TI  - Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant
      chemotherapy for locally advanced rectal cancer.
AB  - The aim of this study was to demonstrate a pathologic complete response (pCR)
      rate of at least 10% with an acceptable toxicity achieved by preoperative
      chemoradiotherapy with 5-fluorouracil (5-FU)/leucovorin in patients with locally
      advanced rectal cancer. Patients were treated by radiotherapy targeting 50 Gy and
      5-FU/leucovorin intravenously during the 1st, 4th and 7th week after start of
      radiotherapy followed by surgery and adjuvant chemotherapy. In 71 evaluable
      patients, the pCR rate was 14.1% (95% CI, 6.0-22.2); the local relapse rate,
      6.1%; the 5-year disease-free survival, 54% and the overall 5-year survival, 68%.
      The most severe adverse events were neutropenia (17%), diarrhoea (17%), infection
      (8%) and fatal cardiovascular function (1%). This therapy yielded a high rate of
      pCR, a low rate of local relapse and a long disease-free and overall survival. To
      increase its feasibility, radiation dose reduction to 45 Gy and administration of
      only two preoperative cycles of chemotherapy is recommended.

PMID- 22966282
TI  - IGF-IR and its inhibitors in gastrointestinal carcinomas (Review).
AB  - The type I insulin-like growth factor receptor (IGF-IR) and its associated
      signaling system play a significant role in tumorigenesis, tumor survival and
      progression, and cancer therapeutic resistance, and thus has provoked great
      interest as a promising target for cancer treatment. In this report we present
      the role of IGF-IR in gastrointestinal carcinomas whose pathology has been
      identified as tightly correlated with an abnormal expression and activation of
      IGF-IR. Reported data from experimental studies suggest the feasibility of
      targeted IGF-IR therapy in gastrointestinal carcinomas. Many types of inhibitors
      against IGF-IR have been developed. Inhibitors with anti-IGF-IR monoclonal
      antibodies and tyrosine kinase inhibitors currently undergoing preclinical and
      clinical evolution are also reviewed.

PMID- 22966283
TI  - Prognostic value of tumour endothelial markers in patients with endometrial
      cancer.
AB  - Endometrial cancer is one of the more frequent and most lethal gynaecological
      cancer types. Since it occurs more frequently in elderly and overweight patients,
      a pre-operative staging method would be beneficial. The growth of solid neoplasms
      is always accompanied by neovascularisation. Tumour endothelial markers (TEMs)
      are a group of recently described endothelial cell surface markers that appear to
      be specific to neoplastic tissue. This study aimed to investigate the potential
      usefulness of TEM assessment in the endometrium by comparing the transcriptional
      expression of TEMs in the normal endometrium with endometroid adenocarcinoma
      tissue. Tissues were lysed and the RNA was extracted, assessed and reverse
      transcribed in one batch. Real-time quantitative PCR was performed for TEM-1, -2,
      -6, -7, -7r and -8. GAPDH, beta-actin and ribosomal protein L13A (RPL13A) were
      used as control genes. TEM-8 showed the highest expression level in all of the
      groups. TEM-1 showed higher expression levels in the normal endometrium than in
      the tumour tissues. For the remaining TEMs, we found a higher expression in the
      cancer samples than in the normal endometria. Statistical significance of this
      difference was achieved for TEM-1, -2 and-7. No clear correlation was noted
      between the tumour stage and the level of TEM-1, -6 and -8 expression. Apart from
      TEM-6, the highest expression in FIGO I cancer stages was noted in the remaining
      TEMs. Our results showed that for most of these tumour endothelial markers, gene
      expression was slightly higher in the endometrial carcinoma tissue samples than
      in the endometrium of normal cycling women. However, with the possible exception
      of TEM-8 and -6, absolute expression levels were generally low, indicating that
      most TEMs may only be specifically expressed in a restricted number of cancer
      types (e.g., colorectal). Therefore, TEMs may not be useful in the context of
      endometrial cancer.

PMID- 22966284
TI  - The use of treosulfan and gemcitabine in the treatment of platinum-resistant
      ovarian cancer.
AB  - The combination of treosulfan and gemcitabine (TG) has been shown to have
      activity in ovarian cancer. These two agents are thought to be synergistic, with
      gemcitabine causing the persistence of treosulfan-induced DNA crosslinks. This
      study aimed to investigate the response rates, survival and toxicity in patients
      with platinum-resistant ovarian cancer treated with TG. A retrospective case note
      review of the patients treated with TG was performed in one cancer centre between
      May 1st, 2000 and November 1st, 2005. Estimates of cumulative survival were
      obtained using the Kaplan-Meier method. Forty-nine patients were identified;
      median age at diagnosis was 55 years (range, 31-72) and the median follow-up was
      45.1 months (range, 12.2-118.3). TG was used as second-, third-, fourth- and
      fifth-line chemotherapy in 15, 19, 13 and 2 patients, respectively. Fifteen
      patients (30.6%) had stable disease; 25 (51%), a partial response; 1 (2%), a
      complete response and 8 (16.3%) had progressive disease. Median survival
      following diagnosis was 45.1 months and the median relapse-free survival was 12
      months. The median survival time from the start of TG was 13.7 months with a
      relapse-free survival of 6.3 months. The median number of cycles given was 7. The
      most common toxicity recorded was myelosuppression. There were no treatment
      related deaths. TG chemotherapy produced favourable response rates in a heavily
      pre-treated group of patients with platinum-resistant epithelial ovarian cancer.
      This doublet warrants further investigation in a phase III trial setting.

PMID- 22966285
TI  - A comparative histopathological study of systemic candidiasis in association with
      experimentally induced breast cancer.
AB  - Systemic candidiasis is a fungal infection which coupled with solid malignancies
      places patients at high risk of succumbing to the disease. Few studies have shown
      evidence of the relationship between systemic candidiasis and malignancy-induced
      immunosuppression disease especially in breast cancer. At present, animal studies
      that exclusively demonstrate this relationship have yet to be conducted. The
      exact causative mechanism of systemic candidiasis is currently under much
      speculation. This study therefore aimed to demonstrate this relationship by
      observing the histopathological changes of organs harvested from female Balb/c
      mice which were experimentally induced with breast cancer and inoculated with
      systemic candidiasis. The mice were randomly assigned to five different groups
      (n=12). The first group (group 1) was injected with phosphate buffer solution,
      the second (group 2) with systemic candidiasis, the third (group 3) with breast
      cancer and the final two groups (groups 4 and 5) had both candidiasis and breast
      cancer at two different doses of candidiasis, respectively. Inoculation of mice
      with systemic candidiasis was performed by an intravenous injection of Candida
      albicans via the tail vein following successful culture methods. Induction of
      mice with breast cancer occurred via injection of 4T1 cancer cells at the right
      axillary mammary fatpad after effective culture methods. The prepared slides with
      organ tissues were stained with hematoxylin and eosin, periodic acidic schiff and
      gomori methenamine silver stains for a histopathological analysis. Grading of
      primary tumour and identification of metastatic deposits, as well as scoring of
      inflammation and congestion in all the respective organs was conducted.
      Statistical tests performed to compare groups 2 and 4 showed that group 4
      exhibited a highly statistically significant increase in organ inflammation and
      congestion (p<0.01). The median severity of candidiasis in the kidneys and liver
      also increased in group 4 as compared to group 2. In conclusion, based on the
      above evidence, systemic candidiasis significantly increased in mice with breast
      cancer.

PMID- 22966286
TI  - Antitumor activity of erlotinib in combination with gemcitabine in in vitro and
      in vivo models of KRAS-mutated pancreatic cancers.
AB  - Erlotinib treatment in combination with gemcitabine is a standard therapy for
      patients with locally advanced pancreatic cancer in many countries, including the
      US and the EU. Since mutations of the K-ras oncogene (KRAS) occur in
      approximately 90% of pancreatic cancers, we examined the antitumor activity of
      erlotinib in combination with gemcitabine in KRAS-mutated pancreatic cancer cell
      lines, HPAC and Capan-1, which have the KRAS mutation G12D and G12V,
      respectively. We analyzed the mode of inhibition of in vitro tumor cell
      proliferation by means of a combination index and found that a combination
      treatment of erlotinib plus gemcitabine had an additive effect in the two cell
      lines. We then examined the effect of erlotinib and gemcitabine on the
      phosphorylation of epidermal growth factor receptor (EGFR). Erlotinib strongly
      suppressed, while gemcitabine augmented the phosphorylation of EGFR, which was
      completely blocked by erlotinib in the two cell lines. An in vivo tumor growth
      inhibition test was then performed using the HPAC tumor xenograft model. The
      combination therapy of erlotinib and gemcitabine resulted in a significant
      inhibition of tumor growth compared with erlotinib or gemcitabine monotherapy. To
      the best of our knowledge, this is the first study to show the combination effect
      of erlotinib and gemcitabine in vivo using a xenograft model of a KRAS-mutated
      pancreatic cancer cell line.

PMID- 22966287
TI  - Adjuvant pegylated interferon alpha-2b therapy for melanoma.
AB  - Although adjuvant high-dose interferon alpha-2b therapy significantly improves
      recurrence-free survival vs. observation in high-risk resected melanoma, the
      overall survival benefit is presently unclear. Pegylation of interferon alpha-2b
      (peginterferon alpha-2b) allows for a reduction in the dosing frequency with
      increased drug exposure. Adjuvant peginterferon alpha-2b therapy has also been
      shown to provide a significant, sustained improvement in recurrence-free survival
      compared with observation in patients with stage III melanoma. We report on the
      use of adjuvant peginterferon alpha-2b (3 MUg/kg/week) in clinical practice in a
      series of 8 patients treated at the Universitatsklinikum Essen in Germany
      following complete resection of primary melanoma at intermediate- and high-risk
      of recurrence (stage II-III). Treatment duration ranged from 2 to 29 months, with
      4 patients receiving long-term therapy (>=24 months). Following treatment, 5
      patients (stage II) remained disease-free at 33, 33, 37, 39 and 43 months from
      the time of diagnosis. In 2 patients, peginterferon alpha-2b was terminated 4 and
      9 months after treatment initiation due to disease progression. Once-weekly
      subcutaneous administration of peginterferon alpha-2b was convenient in all
      patients. In 3 patients experiencing adverse events, dose reductions led to a
      resolution of symptoms and enabled treatment to continue long-term. Three further
      patients discontinued therapy due to adverse events at 2, 8 and 27 months of
      therapy (persistent elevation of gamma-glutamyl transpeptidase, liver
      transaminase elevation and urosepsis); dose modifications were not applicable in
      these patients. Thus, long-term adjuvant peginterferon alpha-2b therapy was
      feasible in the clinical practice setting and was generally well tolerated in
      these intermediate- and high-risk melanoma patients.

PMID- 22966288
TI  - alpha-fetoprotein-producing endometrial adenocarcinoma without an obvious
      hepatoid component.
AB  - Endometrial carcinomas producing alpha-fetoprotein (AFP) are extremely rare. We
      report a case of AFP-producing, Grade 2 endometrioid adenocarcinoma without an
      obvious hepatoid component. A 59-year-old multiparous woman presented with
      abdominal swelling. The serum level of AFP was 1292.8 ng/ml. Magnetic resonance
      images of the pelvis showed a markedly enlarged uterus, with a tumor growing
      exophytically within the endometrial cavity. Total abdominal hysterectomy and
      bilateral salpingo-oophorectomy were performed. The histopathological examination
      demonstrated a Stage IIA, Grade 2 endometrioid adenocarcinoma without an obvious
      hepatoid component. The endometrioid adenocarcinoma cells were partly positive
      for AFP immunoreactivity. The patient received adjuvant chemotherapy and was
      disease-free 60 months after the operation. This case confirms the existence of
      AFP-producing endometrioid adenocarcinomas without hepatoid features.

PMID- 22966289
TI  - Adjuvant pamidronate therapy prevents the development of bone metastases in
      breast cancer patients with four or more positive nodes.
AB  - Bisphosphonates are strongly efficacious in inhibiting osteoclast bone resorption
      and have beneficial effects on bone metastasis. Due to their mechanism of action,
      bisphosphonates are expected to prevent the development of bone metastases in
      breast cancer patients. Pamidronate is a potent inhibitor of osteoclast activity.
      We examined whether pamidronate was able to prevent the development of bone
      metastases in breast cancer patients at high risk for bone metastasis. Between
      1997 and 2001, 90 patients with primary breast cancer with >=4 positive nodes
      were assigned to receive 45 mg pamidronate 4 times every 2 weeks (33 patients) or
      standard follow-up (57 patients) based on patient self-preference. Patients
      underwent surgery and adjuvant therapy. The characteristics of the patients in
      the two groups were well-balanced. The median follow-up period was 5 years. Bone
      metastases were detected in 12.1% of patients in the pamidronate group and 40.4%
      in the control group (p=0.005). Distant metastases (36.4 vs. 56.1%, p=0.071) and
      non-osseous metastases (33.3 vs. 52.6%, p=0.077) were detected at a lower
      frequency in the pamidronate group. Thus, the rate of bone metastasis-free
      survival was significantly higher in the pamidronate group (85.9 vs. 64.0% at 5
      years, p=0.023). Overall and disease-free survival rates did not differ between
      the two groups. In the pamidronate group, the incidence of bone metastases was
      significantly reduced and bone metastasis-free survival was significantly higher.
      Adjuvant pamidronate therapy therefore prevents the development of bone
      metastases in breast cancer patients with >=4 positive nodes.

PMID- 22966290
TI  - Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical
      response and survival in advanced colorectal cancer patients receiving
      bevacizumab with modified FOLFOX6.
AB  - For individualized bevacizumab-based therapy, non-invasive biomarkers are
      necessary. This study assessed the predictive value of plasma vascular
      endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-1 and sVEGFR-2
      levels as biomarkers for clinical response and survival in advanced colorectal
      cancer (CRC) patients treated with bevacizumab and modified FOLFOX6 (mFOLFOX6).
      Forty-six unresectable advanced CRC patients and 20 healthy controls were
      included in this study. CRC patients were treated with bevacizumab and mFOLFOX6.
      Pretreatment plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were measured using the
      multiplex immunoassay. Plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were
      significantly higher in CRC patients than in the healthy subjects. The plasma
      sVEGFR-1 levels in the responder patients [complete response (CR)/partial
      response (PR)] and stable disease (SD) patients were significantly lower than
      those in the progressive disease (PD) patients (CR/PR vs. PD, p=0.025; SD vs. PD,
      p=0.032), while the plasma VEGF-A and sVEGFR-2 levels did not show any
      significant differences between the two groups of patients. Patients with higher
      sVEGFR-1 levels showed a significantly poorer progression-free survival (PFS) and
      overall survival (OS) than those with lower VEGFR-1 levels. In contrast, VEGF-A
      and sVEGFR-2 did not show any significant relationship between PFS and OS
      according to the status of each level. In the multivariate Cox proportional
      hazard regression analysis, sVEGFR-1 levels showed a significant relationship
      between PFS and OS. These results suggest that plasma sVEGFR-1 levels have a
      predictive value for clinical response and survival in advanced CRC patients
      treated with bevacizumab and mFOLFOX6. Larger scale studies are needed to further
      validate our results.

PMID- 22966291
TI  - High expression of thymidine phosphorylase in basal-like breast cancers: Stromal
      expression in EGFR- and/or CK5/6-positive breast cancers.
AB  - Expression of the estrogen receptor (ER), the progesterone receptor (PgR) or the
      human epidermal growth factor receptor-2 (HER2) in tumors is a good prognostic
      marker for breast cancer patients. However, approximately 15-20% of breast cancer
      patients have triple-negative breast cancer (TNBC; negative for ER, PgR and
      HER2), and efficient therapeutic modalities for these patients are under
      investigation. We focused on thymidine phosphorylase (TP), an enzyme metabolizing
      5'-DFUR, an intermediate of capecitabine, to 5-fluorouracil in order to
      investigate the application of well-known therapeutics for TNBC. Results of a
      gene expression analysis showed that TP expression in TNBC and basal-like breast
      cancer (BLBC) was higher than that of other subtypes. Immunohistochemically, the
      high expression of TP in TNBC and BLBC reflected expression in stromal but not
      tumor cells. Notably, a high TP expression was observed in the stromal cells of
      EGFR- and/or CK5/6-positive breast tumors. Our present results showing a high
      expression of TP in BLBC indicate that capecitabine-based chemotherapy would be
      of benefit for patients with TNBC.

PMID- 22966292
TI  - Human papillomavirus genotypes in penile cancers from Japanese patients and HPV
      induced NF-kappaB activation.
AB  - The causal relationship between chronic inflammation and cancer is widely
      accepted. Numerous investigations have identified nuclear factor-kappaB (NF
      kappaB) as an important modulator in driving chronic inflammation to cancer. This
      study aimed to determine the prevalence of human papillomavirus (HPV) in penile
      cancer in Japanese patients and whether NF-kappaB is subsequently overexpressed
      in penile cancer. Thirty-four specimens of penile tissue (16 malignant and 18
      benign cases) were examined to determine the association of HPV infection. An in
      situ hybridization (ISH) method was used to detect and localize HPV-DNA. A
      sensitive HPV polymerase chain reaction (PCR) procedure was used for the
      detection of HPV-DNA, and DNA sequencing was used to identify the HPV genotype.
      HPV-DNA was detected in 37.5 and 75% of cases of penile cancer, using ISH and
      PCR, respectively. Our efforts to detect HPV genotypes were unsuccessful as HPV
      DNA could not be extracted from these materials. Using ISH, a prevalence of 68.2%
      of HPV infection was found in penile cancer in Kenyan patients in east Africa. In
      the present study, all 9 HPV-positive cases, (100%) were NF-kappaB-positive in
      the nucleus and/or cytoplasm. In contrast, of the 25 HPV-negative cases, 15 (60%)
      were NF-kappaB-positive in the nucleus and/or cytoplasm. Therefore, ISH is a
      method which is able to prove infection of a large quantity of HPV more
      effectively when compared with PCR. Thus, a large quantity of HPV infection leads
      to the activity of NF-kappaB. The most prevalent genotype was the HPV-22 found in
      83.3% of the penile cancer cases. In addition, HPV-11 was found in 81.8% of the
      non-cancer cases. For cases with a high level of infection, the activity of NF
      kappaB increased compared with those with a low level of HPV infection.

PMID- 22966293
TI  - Chemoprevention of 1,2-dimethylhydrazine-induced colonic preneoplastic lesions in
      Fischer rats by 6-methylsulfinylhexyl isothiocyanate, a wasabi derivative.
AB  - The preventive effects of dietary exposure to a wasabi derivative 6
      methylsulfinylhexyl isothiocyanate (6-MSITC) during the initiation and post
      initiation phases on the development of 1,2-dimethylhydrazine (DMH)-induced
      colonic aberrant crypt foci (ACF), and beta-catenin-accumulated crypts (BCAC)
      were investigated in male F344 rats. To induce ACF and BCAC, rats were given four
      weekly subcutaneous injections of DMH (40 mg/kg body weight). The rats also
      received diets containing 200 or 400 ppm 6-MSITC during the initiation or post
      initiation phases. The experiment was terminated 12 weeks after the start. DMH
      exposure produced a substantial number of ACF (323.8+/-69.7/colon) and BCAC
      (3.80+/-1.05/cm(2)) at the end of the study. Dietary administration of 6-MSITC at
      a dose of 400 ppm during the initiation phase caused a significant reduction in
      the total number of ACF (52% reduction, P<0.0001), larger ACF (4 or more crypt
      ACF) (58% reduction, P<0.001) and BCAC (76% reduction, P<0.00001). The dietary
      exposure to 6-MSITC significantly reduced the size (crypt multiplicity) of BCAC
      during both initiation and post-initiation treatment when compared to group 1
      treated with DMH alone. Immunohistochemically, 6-MSITC administration lowered the
      proliferating cell nuclear antigen labeling index in ACF and BCAC. In addition,
      protein levels of hepatic cytochrome P-450 isozymes at 24 h after 6-MSITC
      exposure were significantly suppressed (P<0.01). The results indicated that 6
      MSITC exerted chemopreventive effects in the present short-term colon
      carcinogenesis bioassay, through alterations in cell proliferation activity and
      drug metabolizing enzyme levels.

PMID- 22966294
TI  - ATP7B expression is associated with in vitro sensitivity to cisplatin in non
      small cell lung cancer.
AB  - Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly
      associated with platinum drug resistance in various solid tumors. However, the
      impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC)
      remains unclear. We investigated in vitro cisplatin (CDDP) sensitivity using the
      collagen gel-droplet embedded culture drug sensitivity test. The ATP7B mRNA
      expression level in each specimen was also examined using real-time polymerase
      chain reaction. The relationship between ATP7B expression and in vitro CDDP
      sensitivity was then evaluated. The ATP7B mRNA expression levels in CDDP
      resistant tumors were significantly higher than those in the CDDP-sensitive group
      (p=0.015; Mann-Whitney U test). Our results suggested that ATP7B expression is a
      promising chemoresistance marker for cisplatin.

PMID- 22966295
TI  - Methylation of the DLEC1 gene correlates with poor prognosis in Japanese lung
      cancer patients.
AB  - The incidence of chromosome 3p gene alterations is one of the most frequent and
      earliest documented events in lung cancer. This study aimed to investigate
      promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene,
      as well as the p16 and CDH1 genes in Japanese lung cancer cases. The methylation
      status of the promoter regions of DLEC1, p16 and CDH1 was investigated using
      methylation-specific PCR. The findings were compared to the clinicopathological
      features of lung cancer. Methylation-specific PCR showed that the DLEC1 promoter
      region was methylated in 65 out of 116 (56%) lung cancers. Patients with DLEC1
      methylated cancer were associated with a significantly worse prognosis than those
      with unmethylated cancer (p=0.0368; hazard ratio=1.83). The p16 methylation
      status correlated with squamous histology (p=0.03) and smoking status (never
      smoker vs. smoker; p=0.0122). Patients with p16 ummethylated cancer harbored more
      EGFR mutations (p=0.0071). The CDH1 promoter region was hypermethylated in 65 out
      of 118 (55.1%) lung cancer cases. However, the CDH1 methylation status was not
      associated with the clinicopathological characteristics of the lung cancer types.
      p16 and CDH1 methylation status did not correlate with survival in the lung
      cancer patients. Thus, in our Japanese cohort, the methylation status of the
      DLEC1 gene was a marker of poor prognosis independent of stage.

PMID- 22966296
TI  - Down-regulation of IL-6, IL-8, TNF-alpha and IL-1beta by glucosamine in HaCaT
      cells, but not in the presence of TNF-alpha
AB  - There is considerable evidence that glucosamine exerts an inhibitory effect on
      inflammatory cytokine expression in cells. Glucosamine has been recommended as a
      promising anti-inflammatory modulator, which has been applied in clinical trials
      for attenuation of the inflammatory process. However, it is unknown whether
      glucosamine reduces the expression of TNF-alpha-induced inflammatory cytokines in
      HaCaT cells. The anti-inflammatory effects of curcumin in HaCaT cells have been
      extensively investigated in several studies. Thus, in this study we investigated
      the expression of IL-6, IL-8, TNF-alpha and IL-1beta in glucosamine-treated HaCaT
      cells, and the effects of glucosamine were compared to those of curcumin-treated
      HaCaT cells. Our data showed that the expression of IL-6, IL-8, TNF-alpha and IL
      1beta was decreased by glucosamine treatment in the HaCaT cells. In contrast, the
      expression of IL-6, IL-8, TNF-alpha and IL-1beta was not attenuated by
      glucosamine treatment in the TNF-alpha-treated HaCaT cells. Notably, curcumin
      induced an increased expression of IL-8 and IL-1beta in the HaCaT cells, but not
      that of IL-6 and TNF-alpha. On the other hand, curcumin attenuated the expression
      of IL-6 and IL-8 in the TNF-alpha-treated HaCaT cells. Our data indicated that
      glucosamine induced the down-regulation of IL-6, IL-8, TNF-alpha and IL-1beta
      expression in the HaCaT cells. However, the stimulation of TNF-alpha abolished
      the inhibitory effects of glucosamine on the expression of inflammatory cytokines
      in the HaCaT cells. Thus, even though glucosamine induces the down-regulation of
      inflammatory cytokines in HaCaT cells, the anti-inflammatory role of glucosamine
      in TNF-alpha-mediated inflammatory skin diseases should be investigated.

PMID- 22966297
TI  - Diffusion-weighted magnetic resonance imaging for assessment after neoadjuvant
      chemotherapy in breast cancer, based on morphological concepts.
AB  - The study aimed to evaluate the utility of diffusion-weighted imaging (DWI) and
      to assess the response of breast cancer patients to neoadjuvant chemotherapy
      (NAC), based on morphological concepts. This retrospective study included 35
      breast cancer patients (36 lesions) who had conventional magnetic resonance
      imaging (MRI), with DWI acquired before and after NAC. The morphological pattern
      of delayed enhancement on MRI before NAC was classified into two types: focal
      mass (FM), and multiple masses and/or non-mass like (MM/NM), based on Breast
      Imaging Reporting and Data System (BI-RADS). Of the 36 tumors, 26 were classified
      as FM and 10 as MM/NM. Tumors were clearly visualized on the initial DWI although
      one case of suspected MM/NM was not observed on DWI following NAC. A correlation
      was found between changes in the apparent diffusion coefficient and response
      rates to NAC in FM tumors (r=0.608, p<0.001), but not in MM/NM tumors (r=0.141,
      p=0.717). There was agreement between MRI findings after NAC and pathological
      findings in 30 of the 36 tumors (83.3%). Thus, we concluded that DWI is
      potentially useful in assessing the response to NAC for breast cancer for tumors
      diagnosed as FM on the initial conventional MRI.

PMID- 22966298
TI  - Signet ring cell-type adenocarcinoma arising in a mature teratoma of the testis.
AB  - A 48-year-old male who presented with an enlarged right scrotum was diagnosed
      with malignant transformation of testicular teratoma. Physical examination
      revealed a right scrotal mass of hard consistency with no inguinal
      lymphadenopathy. Since prepuberty, his right testis had been larger than the left
      one, with no pain or tenderness. Computed tomography and bone scan revealed
      retroperitoneal lymphadenopathy and multiple bone metastases. Right orchiectomy
      was performed immediately, and a pathological examination revealed a mature
      teratoma associated with adenocarcinoma, showing signet ring cell
      differentiation. Cisplatin-based combination chemotherapy was administered;
      however, the metastatic lesions progressed, and the patient succumbed to the
      disease after 15 months. Only a few cases of primary malignant transformation of
      teratoma in the testis have been reported, and this is the first case report of
      primary malignant transformation of teratoma in the testis with signet ring cell
      type differentiation.

PMID- 22966299
TI  - Hypermethylation of the large tumor suppressor genes in Japanese lung cancer.
AB  - Large tumor suppressor (LATS) 1 and 2 are tumor suppressor genes implicated in
      the regulation of the cell cycle. The methylation statuses of the promoter
      regions of these genes were studied in Japanese lung cancers. The methylation
      statuses of the promoter regions of LATS1 and LATS2 were investigated by
      methylation-specific PCR. The findings were compared to clinicopathological
      features of lung cancer. Methylation-specific PCR showed that the LATS1 promoter
      region was hypermethylated in 95 out of 119 (79.8%) lung cancers. The methylation
      status of LATS1 was significantly associated with squamous histology (p=0.0267)
      and smoking status (never smoker vs. smoker; p=0.0399). LATS1-ummethylated
      patients harbored more EGFR mutations (p=0.0143). The LATS2 promoter region was
      hypermethylated in 160 out of 203 (78.8%) lung cancers. However, the methylation
      status had no association with the clinicopathological characteristics of the
      lung cancers cases. Both the LATS1 and LATS2 methylation statuses did not
      correlate with survival of lung cancer patients. Thus, the EGFR methylation
      status of the LATS genes has limited value in Japanese lung cancers.

PMID- 22966300
TI  - Synthesis and biological evaluation of novel dibenzofluorene derivatives as
      anticancer agents.
AB  - The novel synthesis of dibenzofluorene has been achieved by a cyclodehydration
      method. Several derivatives have also been prepared using this hydrocarbon. These
      compounds have been tested against a number of cancer cell lines in vitro, and
      useful selectivity has been observed.

PMID- 22966301
TI  - A combination of green tea extract, specific nutrient mixture and quercetin: An
      effective intervention treatment for the regression of N-methyl-N-nitrosourea
      (MNU)-induced mammary tumors in Wistar rats.
AB  - Mammary tumors were developed by intraperitoneal injection of N-methyl-N
      nitrosourea (MNU) in 21-day-old, sexually immature female Wistar rats. Injection
      of MNU was repeated 14 weeks after the first one. When palpable tumors were
      evident in all of the rats, various dietary treatments were initiated for a
      period of 8 weeks. The treatments were designed to provide 30 mg green tea
      extract either alone or as a nutrient mixture (E). E was then expanded to include
      either a nutrient supplement (N), quercetin (Q) or both (N+Q). At the end of the
      treatment, tumor size/rat measured in the live rats was significantly lower in
      the groups receiving E, E+Q, E+N and E+N+Q than in the positive control (PC)
      group which did not receive any dietary treatment. Tumor number/rat, tumor
      volume/rat and tumor weight/rat were evaluated after sacrificing the rats on the
      60th day. The rats receiving E+N+Q showed significantly lower values for the
      three parameters as compared to the PC group. The PC group showed 24 carcinomas
      mostly of grade III severity, while the E+N+Q group had only 6 carcinomas, all of
      which were of grade II severity.

PMID- 22966302
TI  - Sonic Hedgehog pathway activity in prostate cancer.
AB  - Abnormal activation of the Sonic hedgehog (Shh) signaling pathway has been
      demonstrated in a number of human tumors, including prostate cancer. The study
      aimed to assess the activity of Shh pathway components (Shh, Gli1, Gli2 and
      Gli3), as well as the proliferation markers FoxA1 and Notch1 during cancer
      progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP). We
      evaluated changes in respective proteins by immunohistochemistry at three time
      points (12, 17 and 21 weeks of age) in the tissue of TRAMP and C57Bl/6 mice.
      Moreover, the expression of mRNA of these proteins was assessed. The present
      study shows a significant age-dependent increase in the number of Shh, Gli1, Gli3
      and FoxA1-positive prostate cells and a decrease in Gli2-positive cells in TRAMP.
      The study also supports the hypothesis that the development of prostate cancer
      and its metastasis is associated with activation of the Shh signaling pathway.

PMID- 22966303
TI  - Serum proteomics and disease-specific biomarkers of patients with advanced
      gastric cancer.
AB  - Gastric cancer is a commonly diagnosed solid tumor which is associated with a
      dismal prognosis making early diagnosis essential. Thus, this study aimed to
      identify novel biomarkers in gastric cancer. Serum of patients with advanced
      gastric cancer was collected according to a predefined schedule: prior to first
      line chemotherapy with epirubicin (50 mg/m(2), day 1), cisplatin (60 mg/m(2), day
      1) and capecitabine (1,000 mg/m(2), twice daily on days 1-14). The serum was
      collected serially before the treatment cycles and then analyzed by SELDI-TOF MS.
      Normal control subjects were matched according to age, gender and serum
      collection. Serum proteomic mass spectrometry data of all subjects were processed
      using the tbimass R-package and compared. We analyzed i) whether proteomic
      profile changes were associated with a response to chemotherapy and survival, and
      ii) whether changes in proteomic profiles occurring during the time period of
      chemotherapy were associated with tumor response. In total, 82 patients with
      adenocarcinoma of the stomach (mean age 57 years, males 69.5%) were treated with
      a mean number of five chemotherapy cycles. The overall tumor response rate,
      complete and partial remission combined, was 37%, median time to progression was
      7 months (95% CI, 6-8) and median overall survival 11 months (95% CI, 9.5-12). By
      comparing 77 serum samples of patients with normal matched controls, we
      identified 32 proteins which discriminated the two groups. By selecting the most
      differentiating proteins, we built a classification model that correctly
      categorized 81% of the gastric cancer patients and 90% of the normal controls.
      Furthermore, we found a statistically significant correlation between the pre
      treatment intensity of serum amyloid-alpha (SAA) and overall survival in gastric
      cancer patients, whereby a low intensity of SAA predicted a longer patient
      survival. A classification model, based on the 32 most discriminating proteins
      differentiating gastric cancer from normal controls, correctly classified
      subjects with relatively high sensitivity and specificity.

PMID- 22966304
TI  - Erlotinib treatment in pretreated patients with non-small cell lung cancer: A
      Phase II study.
AB  - Erlotinib is an oral, small-molecule targeting therapy that inhibits epidermal
      growth factor tyrosine kinase receptors. Erlotinib has been administered for the
      treatment of advanced pancreatic cancer and non-small cell lung cancer. In the
      present trial, erlotinib was administered as second-line monotherapy in
      pretreated patients with advanced non-small cell lung cancer. Our objectives were
      to determine response, survival and toxicity. Fifty-four patients pretreated with
      cisplatin or its analogue-based combinations were evaluated. The disease stage of
      the patients was IIIB and IV. Thirty-eight patients were male, 16 were female,
      the median age was 65 years, and the WHO performance status was 0-2. Twenty-five
      cases were adenocarcinomas, 19 squamous cell carcinomas and 10 were
      undifferentiated. Erlotinib was administered at a dose of 150 mg daily. In case
      of intolerable adverse reactions, the dose was either reduced to 100 mg daily or
      treatment was interrupted for a maximum of two weeks. A partial response was
      observed in 10 (18.52%) and stable disease in 40 (74.07%) patients. The median
      time to disease progression was 3 months (95% CI 1.7-10.3), and the median
      survival was 6 months. Concerning toxicity, 53 patients (98.15%) developed a
      grade 1-2 skin rash, and 1 (1.85%) grade 3. Diarrhea occurred in 9 (16.67%)
      patients, nausea and vomiting in 4 (7.41%) and gastritis in 2 (3.70%). The
      majority of patients tolerated the erlotinib treatment. Of note were the 18.52%
      response rate and 74.07% stable disease.

PMID- 22966305
TI  - Abundance of a distinct cluster of telomere t-stumps in advanced breast cancer
      cell line.
AB  - Breast tumors are the second major cause of cancer-related death in women
      worldwide. These tumors are aggressive, leading to metastatic cancers that are
      heterogeneous in nature, with numerous subtypes. The basal-like tumor subtype
      invariably shows unfavorable prognosis and is often characterized by the lack of
      estrogen, progesterone and HER2 receptors. These cancer types do not respond to
      the current targeted therapies. Therefore, the need for the discovery of novel
      diagnostic markers/therapeutic targets is of paramount importance.
      Immortalization of breast tumor cells leading to advanced stage cancer is one of
      the pivotal steps in breast cancer and telomeres/telomerase play a critical role
      in this process. Using single telomere length analysis, cell lines with a basal
      like phenotype encompassing immortalized/non-tumorigenic MCF10A and
      invasive/metastatic MCF10CA1 along with the MCF-7 cell line were examined for the
      presence of a unique class of telomere t-stumps. Telomerase activity, protein
      levels of telomerase and bulk telomere lengths were assessed in the above
      mentioned cell lines. This is the first study describing the existence of a
      distinct class of extremely short telomeres termed 't-stumps' in breast cancer
      cell lines. The cell lines MCF10A and MCF10CA1 showed distinct telomeric bands in
      the molecular size range of 100-1,000 bp, whereas the MCF-7 cell line showed very
      low levels of t-stumps. Of note is that only the highly invasive/metastatic
      cancer cell line MCF10CA1 exhibited an abundance of a cluster of t-stumps with a
      size distribution range of 500-700 bp. These unique t-stumps observed in the
      advanced breast cancer cell line may serve as a novel diagnostic marker and also
      form a key molecular target for novel anticancer therapy.

PMID- 22966306
TI  - Chemosensitivity of lung cancer: Differences between the primary lesion and lymph
      node metastasis.
AB  - In this study, chemosensitivity tests were performed on both primary lesions
      (PLs) and lymph node metastases (LMs) from surgically resected non-small cell
      lung cancer (NSCLC). Differences between the results obtained were evaluated.
      Operative specimens were obtained from 13 patients with NSCLC [6 with squamous
      cell carcinoma (SQ) and 7 with adenocarcinoma (AD)] whose lymph nodes were
      confirmed to be positive for metastasis. Both the PL and LM from the same patient
      were examined immediately after resection. The collagen gel droplet-embedded
      culture drug sensitivity test (CD-DST) was used as the chemosensitivity test
      against six anticancer drugs [5-fluorouracil (5-FU), cisplatin, gemcitabine,
      docetaxel, vinorelbine and SN-38 (an active metabolite of irinotecan)]. When the
      growth rate, determined by the T/C ratio (T, signal for viable cells in the
      treated group and C, signal in the control) was less than 50%, the tumor cells
      were considered to be sensitive to the drug. Only in 4 cases (2 SQ and 2 AD) was
      the chemosensitivity of the primary lesion identical to that of LM. In the SQ
      cases, chemosensitivity of the primary lesions to 5-FU tended to be consistent
      with that of LMs. In contrast, the primary lesions in 4 of the 7 AD cases were
      negative for chemosensitivity to 5-FU; however, LMs were sensitive. In many
      cases, the chemosensitivity of the PLs to each anticancer drug differed from that
      of the LMs. In conclusion, both primary and metastatic tumors should be examined
      to ensure maximum clinical efficacy of in vitro drug-sensitivity testing for
      adjuvant chemotherapy after complete resection of n1 and n2 NSCLC.

PMID- 22966307
TI  - Influence of 5-fluorouracil on ferredoxin reductase mRNA splice variants in
      colorectal carcinomas.
AB  - 5-Fluorouracil (5-FU) is a frequently used antitumor drug. Recently, it has been
      shown that mRNA and protein levels of the ferredoxin reductase gene (gene, FDXR;
      protein, FR) increase drastically after 5-FU treatment in various cell lines
      including colorectal cancer. The induction is mediated by p53 and enhanced
      reactive oxygen species (ROS)-associated apoptosis. Thus, knowledge about FDXR
      expression in human tissue and expression of the known splice variants is
      critical for understanding this finding. A sensitive and specific reverse
      transcriptase polymerase chain reaction (RT-PCR) assay for quantification of FDXR
      mRNA levels including the splice variants, a biological active variant (-18 bp)
      and an inactive variant (+18 bp), was developed and used to measure mRNAs after 5
      FU chemotherapy in colorectal tissues of 40 cancer patients prior to and after
      treatment with 5-FU for 14 days. Before treatment, the great majority of normal
      tissues expressed the splice variants in a 100:1 ratio in favor of the -18
      variant similar to what has been reported for other tissues. In tumors, the mRNA
      levels of total FDXR and splice variants were approximately 2-fold higher
      compared to the normal tissue. After 5-FU treatment, levels of the +18-variant
      increased 17-fold in tumors and 31-fold in normal tissues, clearly shifting the
      ratio towards the +18-form. 5-FU-mediated -18-variant induction (>1) in normal
      (12/17) and tumor tissues (12/16) was apparently associated with response, while
      a balanced ratio (0.1-2) was associated with 5-FU resistance (n=5) based on the
      histological evaluation of the tissues.

PMID- 22966308
TI  - Evaluation of patients with clinically detected recurrence of rectal carcinoma:
      Current practice patterns of colorectal surgeons.
AB  - The optimal evaluation of patients with clinically suspected recurrence of rectal
      carcinoma following initial treatment has yet to be determined. We documented the
      intensity of the extent-of-disease workup conducted by colorectal surgeons when
      their patients with rectal carcinoma develop clinical evidence of metastases. A
      custom-designed questionnaire was mailed to all 1,795 members of the American
      Society of Colon and Rectal Surgeons. Subjects were asked which laboratory tests
      and imaging studies they would order for one of their own generally healthy
      patients with a suspicious abnormality found during surveillance testing. The
      tests most frequently recommended were computed tomography and serum
      carcinoembryonic antigen level. Few tests were recommended by >90% of
      respondents. There is no consensus among experts in this common situation.

PMID- 22966309
TI  - alpha(1,2)fucosylation in human colorectal carcinoma.
AB  - Lewis(b) and Lewis(y) (Le) antigens are known to be elevated in colorectal
      tumours. Alterations in the catalytic behaviour of GDP-L-fucose:beta-D
      galactoside alpha(1,2)fucosyltransferase [alpha(1,2)FT, EC: 2.4.1.69], the key
      enzyme in their synthesis, have been suggested as being responsible for these
      changes. In particular, an aberrant tumour-specific alpha(1,2)FT activity that
      converts Le(a) and Le(x) to Le(b) and Le(y) determinants, respectively, has been
      reported in colorectal cancer tissues. To clarify the catalytic function of this
      enzyme during colorectal tumorigenesis, we analyzed alpha(1,2)FT activity levels
      in healthy and tumour colon specimens using different acceptor substrates and
      determined the kinetic properties of the enzyme. To complete the study, the
      aberrant Le(a)/Le(x) alpha(1,2)fucosylation was determined in healthy and tumour
      colorectal tissues. A correlation analysis between the activity levels and
      various standard clinicopathological features, such as tumour stage, was also
      carried out to elucidate the role of these activities in tumour progression. The
      results obtained confirm the enhanced alpha(1,2)fucosylation in colorectal
      neoplastic tissues and the importance of the aberrant Le(a)/Le(x) alpha(1,2)FT
      activity in this increase. However, taking into account the high levels of
      Le(a)/Le(x) fucosylation observed in healthy control tissues, we must rule out
      the idea of a colorectal tumour-specific alpha(1,2)FT. On the other hand, no
      significant association was observed between alpha(1,2)FT activity levels and the
      clinicopathological characteristics. Overall, our results suggest that
      alpha(1,2)FT activity plays a critical role in the accumulation of Le(b) and
      Le(y) antigens in human colorectal carcinoma.

PMID- 22966310
TI  - Aggressive osteoblastoma of the sphenoid bone.
AB  - For osteoblastoma, with its predilection for the spinal column and appendicular
      skeleton, the skull is an unusual site, and paranasal sinus involvement is very
      rare. Herein, we report on a case in which the disease was located within the
      sphenoid bone. To the best of our knowledge, this is the 4th reported case of
      osteoblastoma with a sphenoid origin (1). We report an osteoblastoma of the
      sphenoid sinus in a 12-year-old girl who presented with exophthalmos. Computed
      tomography (CT) demonstrated an expansile lesion of the sphenoid which caused the
      orbital contents to be compressed and deviated to the right. In the magnetic
      resonance imaging scan, the lesion was found to invade the cranial base in the
      frontal and temporal region, approximating to the cavernous sinus and internal
      carotid artery on the right. Bilateral fronto-orbital craniotomy was performed.
      Histologically, the lesion was composed of proliferating osteoblasts along with
      vascular stroma. The tumor was described as an aggressive osteoblastoma. In the
      follow-up CT four months later, a pathological mass was observed in the area of
      the nasal septum, and a signal void was present on all sequences in the densely
      sclerotic areas. A second resection was performed. The patient has been disease
      free for 61 months. Herein, we present the diagnosis and management of this
      unusual lesion. The histopathology and the imaging characteristics are shown.

PMID- 22966311
TI  - Biological similarities between murine chemical-induced and natural human bladder
      carcinogenesis.
AB  - The present study investigated the similarities between rodent and human
      urothelial carcinogenesis models using DNA content, p53 and Ki-67
      immunoexpression as surrogate markers of bladder carcinogenesis. Following N
      butyl-N-(4-hydroxybutyl)-nitrosamine exposure, 49 human cystectomy specimens of
      bladder cancer and 53 rat bladder specimens were studied. All of the tumours and
      adjacent mucosa present in each specimen were evaluated. High similarities were
      observed between the rodent urothelium carcinogenesis process and the
      corresponding process in humans, in regards to the histopathological features and
      biological alteration profile: DNA aneuploidy, p53 overexpression and high
      proliferative index measured by Ki-67 immunoexpression. Despite these
      similarities, a higher frequency of alterations was observed in earlier stages in
      the rat chemical-induced carcinogenesis, namely in 5c aneuploid cells, p53
      overexpression and higher Ki-67 labelling index. These results confirm that this
      experimental animal model is a suitable and reproducible model of bladder
      carcinogenesis, particularly in regards to high-risk non-invasive and invasive
      urothelial carcinomas. These features mandate its use in the identification of
      new molecular targets and evaluation of tumour response to new cytotoxic drugs or
      drug combinations in bladder cancer therapeutic intervention.

PMID- 22966312
TI  - (99m)Tc-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant
      chemotherapy in locally advanced breast cancer: A quantitative analysis.
AB  - To evaluate the tumor response to neoadjuvant chemotherapy, (99m)Tc-sestamibi
      breast scintigraphy was proposed as a quantitative method. Fifty-five patients
      with ductal carcinoma were studied. They underwent breast scintigraphy before and
      after neoadjuvant chemotherapy, along with clinical assessment and surgical
      specimen analysis. The regions of interest on the lesion and contralateral breast
      were identified, and the pixel counts were used to evaluate lesion uptake in
      relation to background radiation. The ratio of these counts before to after
      neoadjuvant chemotherapy was assessed. The decrease in uptake rate due to
      chemotherapy characterized the scintigraphy tumor response. The Kruskal-Wallis
      test was used to compare the mean scintigraphic tumor response and histological
      type. Dunn's multiple comparison test was used to detect differences between
      histological types. The Mann-Whitney test was used to compare means between
      quantitative and qualitative variables: scintigraphic tumor response vs. clinical
      response and uptake before chemotherapy vs. scintigraphic tumor response. The
      Spearman's test was used to correlate the quantitative variables of clinical
      reduction in tumor size and scintigraphic tumor response. All of the variables
      compared presented significant differences. The change in (99m)Tc-sestamibi
      uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy,
      may be used as an effective method for evaluating the response to neoadjuvant
      chemotherapy, since this quantification reflects the biological behavior of the
      tumor towards the chemotherapy regimen. Furthermore, additional analysis on the
      uptake rate before chemotherapy may accurately predict treatment response.

PMID- 22966313
TI  - Potential antioxidant and antiproliferative activities of a hot-water extract
      from the root of Tonh khidum.
AB  - In this study, for the first time, the possible antioxidant and antiproliferative
      activities of a hot-water extract (TW100) from the root of Tonh khidum (Actinidia
      kolomikta Maxim) were examined in vitro. Total phenolic compound, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical-scavenging activity and superoxide dismutase (SOD)
      like activity assays were utilized to investigate its antioxidant activity. As a
      result, TW100 showed a strong antioxidant activity. The total phenolic content of
      TW100 was 143 MUg gallic acid equivalents/mg. The SOD-like activity of TW100 was
      666,667 U/g extract, and the DPPH radical-scavenging activity was 129 MUg/ml at
      EC(50) which was one third of vitamin E (40 MUg/ml). The antiproliferative
      effects and ability of the extracts to induce apoptosis were studied in vitro
      using human cervical cancer ME-180 cells. Results showed that TW100 inhibited the
      proliferation of ME-180 cells in a dose- and time-dependent manner except at a
      low concentration (10 MUg/ml) with an EC(50) at 24, 48 and 72 h of 36.28, 30.55
      and 29.78 MUg/ml, respectively. TW100 also induced apoptosis as determined by a
      nuclear fragmentation assay and an analysis of flow cytometry. In conclusion, the
      hot-water extract from the root of Tonh khidum possesses potential antioxidant
      and antiproliferative activities.

PMID- 22966314
TI  - Surgical considerations in regard to Denonvilliers' fascia.
AB  - In this study, the region between the prostate and the rectum was examined. We
      reviewed, macroscopically, the clinical anatomy of the perioperative regions and
      excised specimens. Moreover, using fixed specimens from three cases of total
      pelvic exenteration, we histologically reviewed the regions between the prostate
      and rectum. Following bladder neck transection, the deferent duct was observed in
      connective tissues that continued to Denonvilliers' fascia. When the prostate was
      pulled ventrally, this connective tissue was identified as a sheet of membrane
      that traversed from the anterior prostate to the dorsal rectum. The dorsal
      surface of the specimen appeared to be covered with a thin membrane, and the
      regions that continued from this thin membrane were judged macroscopically as a
      stump. Between the prostate and the rectum, intricate connective tissue was
      present in the fixed specimen that was removed via a total pelvic exenteration.
      This connective tissue continued to the connective tissue surrounding the seminal
      vesicles and prostate. The complex connective tissue was present anatomically
      between the prostate and rectum. As a result of the surgical procedures, this
      connective tissue was identified surgically as Denonvilliers' fascia.

PMID- 22966316
TI  - Gastric carcinoma in China: Current status and future perspectives (Review).
AB  - Gastric cancer is one of the most frequently occurring cancers in China, with an
      estimated 380,000 new cases each year, accounting for more than 40% of the
      worldwide annual cancer incidence. There is geographical clustering of the
      distribution of gastric cancer in China, with most of the high-risk areas being
      rural. D2 resection is the standard lymphadenectomy for curative resection in
      China, but more extensive lymphadenectomy is conducted for selected patients.
      Perioperative chemotherapy, postoperative chemotherapy or chemoradiotherapy can
      be combined with surgery. It remains uncertain which option is best, but if
      surgery is insufficient, adjuvant chemoradiotherapy is recommended. In the
      palliative setting, although there is no standard first-line chemotherapy,
      regimens based on taxane, oxaliplatin or capecitabine, or the epirubicin,
      cisplatin, 5-fluorouracil regimen and its modifications are the most common
      options selected by Chinese oncologists. Several studies to evaluate target
      therapy are ongoing, but it is too early to draw any conclusions. However, the
      development of target therapy is likely to become a milestone in the treatment of
      gastric cancer.

PMID- 22966315
TI  - Melanoma biomarkers: Vox clamantis in deserto (Review).
AB  - Detecting malignant melanoma at an early stage, monitoring therapy, predicting
      recurrence and identifying patients at risk for metastasis continue to be a
      challenging and demanding objective. The last two decades have witnessed
      innovations in the field of melanoma biomarkers. However, global agreement
      concerning monitoring and early detection has yet to be reached. This is a review
      of the current literature regarding melanoma biomarkers including demographic,
      clinical, pathological and molecular biomarkers that are produced by melanoma or
      non-melanoma cells. A number of these biomarkers demonstrate promising results as
      possible methods for early detection, predicting recurrence and monitoring
      therapy. Other biomarkers appear to be promising for identifying patients at risk
      for metastasis. We reviewed the most pertinent information in the field thus far
      and how this knowledge can impact, or not, the management of melanoma patients
      prognostically and therapeutically.

PMID- 22966317
TI  - Primary cutaneous apocrine carcinoma arising within a congenital nevus: Keratins
      and filaggrin expression suggesting differentiation into the secretory cells of
      apocrine glands.
AB  - Primary cutaneous apocrine carcinoma (PCAC) is a rare neoplasm of skin
      appendages. To determine the differentiation of apocrine carcinoma, we studied
      the expression of epithelial keratins and filaggrin immunohistochemically using
      10 anti-keratin antibodies againt keratin (K) 1, 7, 8, 10, 14, 15, 16, 17, 18, 19
      and the anti-filaggrin antibody. PCAC demonstrated strong positivity for K7, K8,
      K18 and K19. These keratins are distributed in secretory cells of normal apocrine
      glands. The tumor cells were negative for K14 and K17. The two keratins exist in
      myoepithelial cells in normal apocrine glands. Results suggest that PCAC shows
      differentiation into secretory cells of apocrine glands, although it does not
      differentiate into myoepithelial cells. K14 is also known as undifferentiated
      keratin, whereas K17 is considered to be a hyperproliferative keratin. Absence of
      the expression of K14 and K17 may reflect an indolent clinical course of PCAC.

PMID- 22966318
TI  - Expression of matrix metalloproteinase-10 in non-metastatic prostate cancer:
      Correlation with an imbalance in cell proliferation and apoptosis.
AB  - Matrix metalloproteinases (MMPs) are associated with cell invasion under various
      physiological and pathological conditions. Among MMPs, MMP-10 is reported to
      correlate with a high pT stage and progression in a variety of cancer types.
      However, the clinical and pathological significance of MMP-10 in human prostate
      cancer tissues remains unclear. This study aimed to clarify the role of MMP-10 in
      non-metastatic prostate cancer. Sixty-three specimens were obtained by radical
      prostatectomy. MMP-10 expression, Ki-67, CD34 and apoptotic cells were examined
      using an immunohistochemical technique and the terminal deoxynucleotidyl
      transferase-mediated nick end-labeling method. The proliferation index (PI),
      apoptotic index (AI), microvessel density (MVD) and cell renewal index
      (CRI=PI/AI) were calculated. The relationship between MMP-10 expression and
      clinicopathological features, as well as PI, AI, MVD and CRI were investigated.
      MMP-10 was mainly detected in cancer cell cytoplasm, and the proportion of MMP-10
      expressing cancer cells (median 13.8%) was significantly higher (P<0.001) than
      non-tumoral gland cells (2.4%). Similarly, the proportion of MMP-10-expressing
      cancer cells was significantly higher (P=0.007) in stage pT3 (median 22.3%) than
      in pT2 (11.3%) tumors and was correlated with blood vessel invasion (P=0.025). In
      addition, its expression level correlated significantly with CRI (r=0.34,
      P=0.001), but not with PI, AI or MVD. Multivariate analysis identified MMP-10
      expression to be closely associated with pT stage (OR 3.76, 95% CI 1.14-12.34,
      P=0.029). Our results suggest that the overexpression of MMP-10 produces an
      imbalance in cancer cell proliferation and apoptosis, thereby contributing to
      cancer cell progression of non-metastatic prostate cancer.

PMID- 22966319
TI  - Irinotecan-based combination chemotherapy for metastatic small intestinal
      adenocarcinoma.
AB  - Metastatic small intestinal adenocarcinoma (SIA) is rare among digestive tract
      malignancies, and a standard therapy has yet to be established. The present study
      described a patient who was treated with irinotecan-based chemotherapy. A 67-year
      old woman with a long history of anemia was diagnosed as having SIA using small
      bowel endoscopy. Tumor invasion of the mesentery and multiple metastases to the
      lungs and peritoneal lymph nodes were detected. Nine courses of chemotherapy,
      each consisting of bolus infusion of 5-fluorouracil at 500 mg/m(2), plus infusion
      of irinotecan at 100 mg/m(2) with l-leucovorin at 20 mg/m(2) on days 1, 8 and 15,
      were administered at 4-weekly intervals postoperatively. After two courses, the
      metastatic nodules in the lungs showed a decrease in number and size, and this
      response continued for over 6 months. Adverse events were manageable during this
      period. The patient succumbed to the disease 12 months after the initial
      diagnosis. The present results therefore suggest that irinotecan-based
      chemotherapy is a potential treatment for metastatic SIA.

PMID- 22966320
TI  - Development of hepatocellular carcinoma in patients with chronic hepatitis C more
      than 10 years after sustained virological response to interferon therapy.
AB  - The risk factors for the development of hepatocellular carcinoma (HCC) in
      patients who have achieved a long-term sustained viral response (SVR) to
      interferon (IFN) are not fully understood. This study aimed to investigate the
      characteristics of patients who developed HCC after 10 years of achieving SVR. We
      retrospectively studied 5 patients with HCC which developed more than 10 years
      after the termination of IFN therapy. The clinical characteristics at the
      induction of IFN therapy were male gender, a mean age of 51.6+/-9.1 years, while
      2 patients were moderate alcohol consumers. None of the 5 patients were positive
      for either HBs Ag or anti-HBc Ab. A histological examination at the initial IFN
      therapy showed the activity scores to be A2 in all cases, and the fibrosis scores
      at least F2. The clinical parameters at the diagnosis of HCC included fluctuating
      transaminase levels in all cases. These levels scarcely fell below the upper
      limits even after SVR was achieved. In 3 patients, liver tissues were obtained at
      the treatment of HCC. These tissues showed marked improvement in both activities
      and fibroses, but severe steatosis in 1 patient. To conclude, chronic hepatitis C
      patients who respond to IFN therapy should undergo long-term follow-up, even
      after the eradication of HCV, with special attention particularly to patients who
      had elevated transaminase levels and steatosis.

PMID- 22966321
TI  - Reduced CD73 expression and its association with altered purine nucleotide
      metabolism in colorectal cancer cells robustly causing liver metastases.
AB  - Liver metastases of colorectal cancers significantly affect the prognoses of
      patients. To further understand the biological aspects of the metastatic
      phenotypes, we established the highly liver-metastatic human colorectal cancer
      cell subline SW48LM2. The subline was established through the serial intrasplenic
      transfer of cells derived from poor but visible hepatic tumor foci formed by
      parental SW48 cells and transferred to NOD/SCID/IL-2Rgammac(null) mice. The
      growth, both under monolayer culture conditions and during the formation of
      subcutaneous tumors, was similar between the two cell lines, although there were
      morphological differences in the in vitro spheroid formation. Of 41 molecules
      reportedly associated positively or negatively with tumor progression, four were
      overexpressed and four were underexpressed in SW48LM2 cells. Notably, this liver
      metastatic cell subline exhibited a strongly reduced expression of the ecto-5'
      nucleotidase CD73 as well as an altered metabolism of purine nucleotides.
      Previous studies showed a positive correlation between CD73 expression and
      metastatic cancer phenotypes. A reduced CD73 expression in tumor cells, however,
      may contribute to obtaining insight into the mechanisms of liver metastases.

PMID- 22966322
TI  - Immunohistochemical study of beta-catenin and functionally related molecular
      markers in tongue squamous cell carcinoma and its correlation with cellular
      proliferation.
AB  - beta-catenin plays an important role in the maintenance of cell adhesion and is a
      key component of the Wnt signaling pathway. However, little is known about its
      prognostic significance or its role in tumor progression in tongue squamous cell
      carcinoma (SCC). This study conducted an immunohistochemical analysis of the
      expression of beta-catenin. Moreover, its possible correlation with clinical
      parameters and with the expression of the functionally related molecular markers
      cyclin D1 and p53 was evaluated in 50 cases of tongue SCC and 10 cases of normal
      tongue epithelium. The ki-67 labeling index (LI) was also examined to evaluate
      cellular proliferation. Our results showed a higher frequency of abnormal beta
      catenin expression, positive cyclin D1 and p53 expression, and a significantly
      higher ki-67 LI in the tongue SCC samples compared with normal tongue epithelium
      (P<0.05). Abnormal beta-catenin and a higher ki-67 expression was significantly
      associated with moderately or poorly differentiated carcinoma (P<0.05). Cyclin D1
      positive immunostaining showed a statistically significant association with lymph
      node metastasis (P<0.05). Furthermore, the abnormal expression of beta-catenin
      significantly correlated with a higher ki-67 LI and p53 expression (P<0.05);
      however, there was no correlation with cyclin D1 expression (P>0.05). Taken
      together, our results suggest that abnormal beta-catenin expression is related to
      the impaired cellular differentiation and proliferation involved in tumor
      progression in tongue SCC.

PMID- 22966323
TI  - BCR translocation to derivative chromosome 2: a new case of chronic myeloid
      leukemia with a complex variant translocation and Philadelphia chromosome.
AB  - The well-known typical fusion gene BCR/ABL is observed in connection with a
      complex translocation event in 5-8% of cases of chronic myeloid leukemia (CML).
      The present study described an exceptional CML case with complex chromosomal
      aberrations not previously observed. Aberrations included a translocated BCR to
      the derivative chromosome 2 [der(2)] that also involved a four-chromosome
      translocation, implying chromosomal regions 1p32 and 2q21, besides 9q34 and
      22q11.2, which were characterized by molecular cytogenetics.

PMID- 22966324
TI  - Chemokine expression in tumor-to-tumor metastasis.
AB  - Chemokines play an important role in cancer metastasis by modulating the
      directional cell movement and migration of tumor cells. The most commonly
      overexpressed chemokine receptor in human cancer is CXCR4. Once activated by its
      ligand CXCL12 (stromal cell-derived factor-1 ligand/SDF1), CXCR4 stimulates
      several key migratory, proliferative and survival signaling cellular pathways.
      CXCR4 is expressed in small-cell lung carcinoma (SCLC) cells and other tumors. To
      further characterize the role of chemokines in tumor-to-tumor metastasis, we
      analyzed the tissue expression of CXCR4 and CXCL12 in the surgical specimen of a
      patient with this phenomenon. We performed immunohistochemical analysis for the
      expression of CXCR4 and CXCL12 in metastatic tumor tissue of a 69-year-old
      Caucasian male with extensive SCLC metastatic to a renal oncocytoma. The
      oncocytoma tissue harboring SCLC showed CXCL12 expression, but not CXCR4. A high
      expression of the two molecules was found in a normal renal parenchymal control.
      Our results suggest that CXCR4 and CXCL12 plays a role in this condition, but
      their expression may be affected by the microenvironment of the harboring
      malignancy. Further characterization of these phenomena is needed to shed light
      on the biological mechanisms of tumor metastasis.

PMID- 22966325
TI  - Role of vascular endothelial growth factor receptor-3/Flt-4 in early-stage
      cervical cancer.
AB  - The present study was designed to investigate the role of vascular endothelial
      growth factor receptor (VEGFR)-3/Flt-4 in the early stages of cervical cancer.
      VEGFR-3/Flt-4 expression, vascular endothelial growth factor (VEGF)-C and VEGF-D
      in the early stages (Ia-IIa) of cervical cancer in 41 patients was examined by
      immunohistochemical analysis. Additionally, the VEGFR-3/Flt-4-marked vascular
      density (MVD) was examined and the relationship of these factors with
      clinicopathological factors was analyzed. VEGFR-3/Flt-4 was found to be expressed
      in lymphatic endothelial cells and, to a certain extent, in vascular endothelial
      cells. The VEGFR-3/Flt-4-positive vessels were largely distributed in the stroma
      surrounding the tumor tissues, and these vessels were morphologically divided
      into blood and lymphatic vessels, respectively. Cancer cells were found to
      express VEGF-C, VEGF-D and VEGFR-3/Flt-4, and their positive expression rate was
      48.7% (20/41), 58.5% (24/41) and 63.4% (26/41), respectively. VEGFR-3/Flt-4
      expression in the cancer cells of the cervical cancer patients in our study was
      found to be correlated to the clinical stage, lymph node metastasis, lymphatic
      invasion and expression of VEGF-C and VEGF-D. However, this expression was
      unrelated to menstrual status, histological grade and histological
      classification. MVD was correlated to the clinical stage and expression of VEGF-C
      and VEGF-D, but was unrelated to menstrual status, histological grade,
      histological classification, lymph node metastasis and lymphatic invasion. In
      conclusion, VEGFR-3/Flt-4 plays an important role in the early stages of cervical
      cancer.

PMID- 22966326
TI  - The human pluripotency gene NANOG/NANOGP8 is expressed in gastric cancer and
      associated with tumor development.
AB  - It is well known that cancer cells exhibit characteristics similar to normal stem
      cells. The majority of tumors frequently overexpress genes commonly found in
      embryonic stem cells. To determine whether the pluripotency gene NANOG and its
      retrogene, NANOGP8, play a role in gastric cancer, we analyzed the NANOG/NANOGP8
      expression profile at the mRNA and protein level in primary gastric tumors. Our
      data demonstrated that overexpression of NANOG/NANOGP8 was consistently detected
      in primary tumors (75%, 30/40) compared to adjacent normal tissues (12.5%, 5/40).
      Furthermore, NANOG/NANOGP8 was highly expressed in the intestinal metaplasia
      (60%, 24/40) and dysplasia tissues (66.7%, 20/30) compared to normal tissues.
      These results suggest that NANOG/NANOGP8 exhibits potential as a biomarker and
      its expression may play an important role in gastric cancer development.

PMID- 22966327
TI  - Diagnostic value of carbohydrate antigens in supernatants and sediments of
      pleural effusions.
AB  - A panel of tumour markers including carcinoembryonic antigen (CEA), carbohydrate
      antigen (Ca)15-3, Ca125 and Ca19-9 were measured in the lysate of sediments and
      in the supernatants of pleural effusions of patients with benign and malignant
      disease. The tumour markers were also measured in the serum of the same patients.
      Of these patients, 32 had benign diseases (12 trasudative effusions associated
      with cirrhosis and 20 with non-malignant exudates: 12 pleuritis and 8 other
      inflammations) and 103 had malignant effusions (37 breast cancers, 29 lung
      cancers, 10 ovary cancers, 6 kidney cancers, 11 mesotheliomas and 10 lymphomas).
      We showed the highest level of CEA in pleural effusions of lung cancer followed
      by that in pleural effusions of breast cancer; whereas Ca15-3 was very high in
      the pleural effusions of breast and lung cancer. Concerning the lysate of
      sediment, CEA was high in the pleural effusions of patients with lung cancer and
      Ca15-3 in those of patients with breast cancer. The other markers are much less
      useful. For the remaining tumours, none of the markers tested appear to aid in
      the diagnosis of disease. In conclusion, our data suggest that the combined
      determination of tumour markers on supernatants and sediments of pleural effusion
      may provide additional information on the nature of pleural effusion, especially
      for cases with negative cytology.

PMID- 22966328
TI  - Hepatic metastasis from bile duct cancer of the ampulla is effectively controlled
      by multidisciplinary treatment including S-1, gemcitabine and bevacizumab: A case
      report.
AB  - The liver is the most common site for recurrent metastases from bile duct cancer
      (BDC) in the ampullary area. However, the optimal chemotherapy regimen for
      recurrent hepatic metastases has not yet been established. An oral combined
      fluoropyrimidine drug, S-1 (tegafur, gimeracil and oteracil), has recently been
      introduced alone or in combination with gemcitabine for BDC. A 67-year-old man
      underwent a pancreaticoduodenectomy (PD) for early stage distal BDC in the
      ampullary area. A small hepatic metastasis developed 8 months after the PD.
      Combined chemotherapy of S-1 (80 mg/m(2)) and gemcitabine (1000 mg/m(2)) was
      started after radiofrequency ablation (RFA) of the hepatic tumor. Although
      complete response was achieved and maintained for 4 months with chemotherapy,
      there was regrowth of the tumor. We performed hepatic segmentectomy for radical
      treatment. Fourteen months after the hepatectomy, metastasis developed again in
      the remnant liver. Bevacizumab was added to the combination chemotherapy with S-1
      and gemcitabine, since the cancer seemed resistant to the chemotherapy alone. The
      patient has been well managed for 3 years by a multidisciplinary treatment with
      surgery, RFA and the combination chemo-therapy on an outpatient basis. This case
      indicates that distal BDC even in an early stage has a more malignant potential
      than anticipated. The multidisciplinary treatment including surgery, RFA and
      combination chemotherapy of S-1, gemcitabine and bevacizumab was effective for
      BDC with hepatic metastasis. This chemotherapy is feasible on an outpatient basis
      and may be one of the treatment options for metastatic BDC.

PMID- 22966329
TI  - Evaluation of contrast-enhanced ultrasonography using perfluorobutane
      (Sonazoid((r))) in patients with small hepatocellular carcinoma: comparison with
      dynamic computed tomography.
AB  - This study aimed to elucidate the efficacy of contrast-enhanced ultrasonography
      (CEUS) with perfluorobutane (Sonazoid((r))) in the diagnosis of hepatocellular
      carcinomas (HCCs), particularly small HCCs, by comparing the results with dynamic
      computed tomography (Dy-CT). Seventy-nine nodules in 69 patients with chronic
      liver disease, suspected as HCCs were studied. The nodules were selected based on
      the results of B-mode ultrasonography and/or Dy-CT conducted between January and
      August 2007. The nodules were divided into two groups: the S-group with tumors
      <=2 cm (49 nodules), and the L-group with tumors >2 cm (30 nodules). Typical HCCs
      were defined, and the nodules were enhanced and shown as defects in the arterial
      and late phase of Dy-CT, respectively. Target lesions were scanned using CEUS,
      and the results were compared with those of Dy-CT. The L-group nodules diagnosed
      as HCCs using Dy-CT were also diagnosed as HCCs using CEUS. In the S-group, the
      diagnostic sensitivity of CEUS was 94.7% and the specificity was 81.8%. We
      diagnosed two liver tumors that were detected by CEUS but not by Dy-CT; biopsies
      revealed one tumor to be a well-differentiated HCC and the other to be an
      atypical adenomatous hyperplasia. The sensitivity and specificity of CEUS against
      HCC were high even in the small-size HCCs. Thus, Sonazoid is useful in the
      screening for small HCCs.

PMID- 22966330
TI  - Resveratrol-induced autophagy in human U373 glioma cells.
AB  - Autophagy is an intracellular protein transport process leading to the
      degradation of organelles and long-lived proteins in eukaryotes. The down
      regulation of autophagy observed in cancer cells has been associated with tumor
      progression. This study investigated autophagy induced by resveratrol, a natural
      compound, in human glioma cells. Glioma cells were exposed to resveratrol, and
      the cell growth and autophagic level were evaluated. Resveratrol inhibited growth
      and induced cell death in U373 glioma cells. When treated with resveratrol,
      glioma cells stably expressing GFP fused to LC3, recruited more GFP-LC3-labeled
      autophagosomes, and the percentage of cells with GFP-LC3-labeled autophagosomes
      increased. Furthermore, in resveratrol-treated glioma cells, pretreatment with
      P38 or ERK1/2 inhibitors reduced the autophagic level, suggesting that
      resveratrol-induced autophagy was positively regulated by P38 and the ERK1/2
      pathway. The Akt/mTOR pathway was not involved in resveratrol-induced autophagy.
      Our results suggest that resveratrol has an anticancer effect on glioma cells by
      inducing autophagy.

PMID- 22966331
TI  - Effect of endothelin-1 on cyclooxygenase-2 expression in human hormone refractory
      prostate cancer cells.
AB  - The present study aimed to explore the effects and possible mechanisms of
      recombinant human endothelin (ET)-1 on cyclooxygenase (COX)-2 expression in human
      hormone refractory prostate cancer PC3 cells. PC3 cells were treated with 100
      nmol/l ET-1 for the indicated times (3, 6, 9, 12 and 24 h) and concentrations
      (0.1, 1, 10 and 100 nmol/l) for 24 h. Moreover, 100 nmol/l ET-1 was used to treat
      PC3 cells alone or in combination with endothelin A receptor (ET(A)R) antagonist
      BQ123 (1 MUmol/l), endothelin B receptor (ET(B)R) antagonist BQ788 (1 MUmol/l),
      MAPK/extracellular signal-regulated kinase kinase (MEK)-selective inhibitor,
      PD98059 (10 MUmol/l), p38 mitogen-activated protein kinase (MAPK) antagonist
      SB203580 (5 MUmol/l) or epidermal growth factor receptor (EGFR) antagonist AG1478
      (0.1 MUmol/l) for 24 h. COX-2 mRNA and protein expression was detected in the PC3
      cells by reverse transcription-polymerase chain reaction and Western blot
      analysis. ET-1 induced a time- and dose-dependent increase in the mRNA and
      protein expression of COX-2 in the PC3 cells. BQ123, LY294002, SC203580 and
      AG1478 prevented the expression of COX-2 in the PC3 cells (P<0.05), while BQ788
      did not. ET-1 induced the up-regulation of COX-2 in the PC3 cells. ET(A)R may be
      involved in the process. Several signaling pathways, including p42/44 MAPK, p38
      MAPK and EGFR, are therefore implicated in the regulation of COX-2 expression.

PMID- 22966332
TI  - Reduced expression of claudin-7 is associated with poor outcome in non-small cell
      lung cancer.
AB  - Claudin-7 is a tight junction protein that plays an important role in
      tumorigenesis, tumor invasion and metastasis. We examined the clinical
      significance of claudin-7 expression in 75 postsurgical non-small cell lung
      cancer (NSCLC) patients. Claudin-7 expression was measured immunohistochemically
      and was found to be high in 25 patients (33.3%) and low in 50 (66.7%). Survival
      was significantly poorer in patients with claudin-7-low than in those with
      claudin-7-high NSCLCs (P=0.024). In particular, survival was significantly poorer
      in patients with claudin-7-low than in those with claudin-7-high squamous cell
      carcinomas (P=0.011). A reduced expression of claudin-7 was associated with poor
      outcome in NSCLCs. Claudin-7 may thus be a useful biomarker and a potential
      therapeutic target in patients with NSCLC.

PMID- 22966333
TI  - Metastasis to gallbladder and adrenal gland of renal cell carcinoma.
AB  - We studied a case of metastasis to the gallbladder and left adrenal gland of
      clear cell-type renal cell carcinoma (RCC) in the right kidney. A polypoid
      gallbladder tumor and left adrenal mass were found 2 years after surgery for
      clear cell-type RCC in a 50-year-old man. The gallbladder tumor and left adrenal
      mass showed hypervascularity on diagnostic imaging. Systemic image screening
      showed no other metastatic lesion. Simple cholecystectomy and left adrenalectomy
      were performed. A histopathological examination showed tumor cells in a
      gallbladder polyp. Furthermore, based on various specific and immunohistochemical
      studies, the patient was pathologically diagnosed to have gallbladder and right
      adrenal gland metastasis of clear cell-type RCC.

PMID- 22966334
TI  - Pharmacokinetics of combination chemotherapy with paclitaxel and carboplatin in a
      patient with advanced epithelial ovarian cancer undergoing hemodialysis.
AB  - Few reports delineate the pharmacokinetics of combination chemotherapy with
      paclitaxel and carboplatin in hemodialysis (HD) patients with epithelial ovarian
      cancer. However, the optimal carboplatin dose and the timing of HD have yet to be
      elucidated. We presented a case of an advanced-stage epithelial ovarian cancer
      patient with chronic renal failure requiring HD. After 4 courses of combination
      chemotherapy consisting of paclitaxel and carboplatin, a partial response was
      obtained; therefore, she underwent interval debulking surgery. Paclitaxel was
      administered for 3 h at a dose of 150 mg/m(2), and carboplatin was administered
      for 1 h at a dose of 4-7 area under the concentration/time curve (AUC), which was
      calculated by the Calvert formula. HD was initiated 24 h after the start of
      administration of carboplatin and performed for a period of 3 h. Pharmacokinetic
      studies showed that the AUCs of free platinum and paclitaxel were 3.48-5.55
      mg.min/ml and 13.5 MUg.h/ml, respectively. Combination chemotherapy consisting of
      paclitaxel and carboplatin is a feasible approach to improving the treatment
      outcome of epithelial ovarian cancer patients with chronic renal failure
      requiring HD. The measurement of free platinum is useful in determining the
      optimal dose of carboplatin in order to obtain an adequate AUC. Determining the
      dose of carboplatin according to the Calvert formula and initiating HD after 24 h
      would ensure a favorable therapeutic effect with limited side effects.

PMID- 22966335
TI  - Phase II study of tri-weekly cisplatin and irinotecan as neoadjuvant chemotherapy
      for locally advanced cervical cancer.
AB  - The present study aimed to assess the antitumor response and safety of a tri
      weekly neoadjuvant chemotherapy regimen consisting of cisplatin and irinotecan
      for the treatment of locally advanced cervical cancer with a bulky mass. Between
      June 2002 and March 2008, 20 patients with locally advanced squamous cell
      carcinoma of the uterine cervix at clinical stage Ib2-IIIb were studied. Two 21
      day cycles consisting of intravenous administration of cisplatin at 70 mg/m(2)
      (Day 1) and irinotecan at 70 mg/m(2) (Days 1 and 8) were performed. Antitumor
      responses, adverse events and the surgery completion rate were investigated. The
      response rate of the 15 stage I-II patients was 86.7%, while that of the 5 stage
      III patients was 20%. Grade 3 or 4 neutropenia was noted in 12 patients, and 4
      patients had grade 3 or 4 anemia. Queasiness and vomiting, as grade 3 or 4 non
      hematotoxic events, occurred in 1 patient, but none of the patients had diarrhea.
      The surgery completion rate was 75%. The present data indicate that the tri
      weekly cisplatin and irinotecan combination neoadjuvant chemotherapy involves
      only controllable toxicity and yields a high response rate, suggesting that this
      combination is a useful therapy regimen.

PMID- 22966336
TI  - Surgical treatments for squamous cell carcinoma of the esophagus reaching to the
      muscularis mucosa or the upper third of the submucosal layer.
AB  - We studied the surgical treatments of patients with either esophageal cancer
      reaching to the muscularis mucosae (m3) or with a slight invasion of the
      submucosa (sm1). We reviewed the records and examined the clinicopathological
      features of 29 patients with m3 or sm1 esophageal squamous cell carcinoma who had
      undergone surgery. Lymph node metastasis was noted in 6.3% (1 patient) of
      patients with m3 cancers and in 38.5% (5 patients) of those with sm1 cancers. The
      incidence of lymph node metastasis was higher in the sm1 than in the m3 group,
      but the difference was not significant. Lymphatic invasion (ly) was noted in
      12.3% (2 patients) of patients with m3 cancers and in 53.8% (7 patients) of those
      with sm1 cancers. The incidence of ly was significantly higher in the sm1 group
      than in the m3 group (P<0.05). In a multivariate analysis of factors for
      predicting lymph node metastasis, the presence of ly was the only significant
      predictor (P<0.05). The preoperative diagnostic accuracies of endoscopic
      ultrasonography (EUS), esophagogastroduodenoscopy (EGD) and an upper
      gastrointestinal series (UGS) for predicting depth of invasion were 27.8, 31.0
      and 41.4%, respectively, with the majority of the misdiagnoses being
      overestimations. In conclusion, we suggested that ly is associated with lymph
      node metastasis in m3 or sm1 esophageal cancer. This association is significant
      for treatment-related decision making.

PMID- 22966337
TI  - Down-regulation of microRNA 10a expression in esophageal squamous cell carcinoma
      cells.
AB  - This study identified significantly down-regulated microRNAs (miRs) specific for
      esophageal squamous cell carcinoma (ESCC) cells. Total RNA was extracted from
      ESCC cell lines (OE21 and TE10) and a non-malignant human esophageal squamous
      cell line (Het1A), and subjected to microarray analysis. Expression levels of
      miRs that showed significant down-regulation in ESCC cells compared to Het1A
      cells based on the comprehensive analysis were analyzed by quantitative reverse
      transcription polymerase chain reaction. Among the significantly down-regulated
      miRs, miR-10a expression levels in the five ESCC cell lines examined were
      significantly lower than in Het1A and the esophageal adenocarcinoma cells. Since
      miR-10a is a specific miR in ESCC, its clinical relevance was examined. Using
      ESCC tumor samples and non-cancerous tissue obtained endoscopically, the
      involvement of miR-10a in the clinicopathological findings was examined. MiR-10a
      expression was comparably down-regulated in the tumors of high-grade
      intraepithelial neoplasm and non-invasive ESCC, while the expression levels were
      elevated in the invasive ESCC tumors. Treatment with a demethylating agent, 5-aza
      2'-deoxycytidine, restored miR-10a expression in OE21 cells. Only a modest
      additive or synergistic effect was observed in the presence of a histone
      deacetylase inhibitor, trichostatin A. These results imply that miR-10a may be
      differentially expressed in ESCC cells and may be involved in ESCC development
      and progression. The unique epigenetic regulation of miR-10a expression can be
      mediated via hypermethylation of the CpG islands proximal to its gene locus, at
      least in certain ESCC cells.

PMID- 22966338
TI  - Pterodon pubescens seed extract induces the cell cycle arrest of leukemic cells
      by deregulating cyclin D1 and E2 mRNA levels.
AB  - Plant-derived compounds are important sources of effective anti-cancer agents.
      Pterodon pubescens is a native Brazilian plant popularly known for its anti
      inflammatory and anti-arthritic effects. The ethanolic extract of its seeds
      (EEPp) is a viscous, brown and fragrant oil containing geranylgeraniol, farnesol,
      naphthalene, dimethyldodecatrienol and vouacapan diterpene derivatives, in
      addition to other compounds. This study investigated the in vitro anti-leukemic
      properties of EEPp using the resistant human leukemia cell line K562. The EEPp
      anti-proliferative effect was demonstrated by the inhibition of DNA synthesis and
      cell growth, and the induction of cell cycle arrest in the G(1) phase.
      Furthermore, cyclin E2 mRNA levels were down-regulated, while those of cyclin D1
      were up-regulated. An EEPp anti-leukemic effect may have also triggered
      apoptosis, as it increased the number of shrunken cells and phosphatidylserine
      cell membrane exposure. These observations suggest that EEPp deregulates cyclin
      D1 and E2 expression, inducing cell cycle arrest and apoptosis of leukemic cells.

PMID- 22966339
TI  - Cyclopentenylcytosine does not enhance cisplatin-induced radiosensitization in
      human lung tumour cells.
AB  - The search for agents that enhance the effect of ionizing radiation has been an
      object of study for decades. In this study, the sensitizing properties of
      cyclopentenylcytosine (CPEC) on radiation and cisplatin-induced
      radiosensitization in human squamous lung carcinoma cells were investigated.
      Human lung tumour SW-1573 cells (SWp, parental; SWg, gemcitabine-resistant) were
      incubated with CPEC and cisplatin and subsequently irradiated with different
      doses of gamma-rays. Clonogenic survival was determined to measure the
      effectiveness of the treatments. CPEC (1 or 2 MUM) treatment for 4 h decreased
      the plating efficiency to 75 and 50% in SWp and SWg cells, respectively. In the
      SWg cells, 0.1 and 1 MUM CPEC for 4 h enhanced the cell killing effect of
      cisplatin. However, an increase was not noted in the SWp cells. Due to the
      moderate toxicity of 1 MUM for 4 h, this CPEC dose was used in the
      radiosensitization experiments. However, CPEC neither radiosensitized the lung
      tumour cells nor enhanced the radiosensitizing effect of cisplatin. A 2-h
      incubation with 4 MUM cisplatin also decreased the plating efficiency to 75-80%
      in the two cell lines. Using this cisplatin dose, radiosensitization was obtained
      in the two cell lines. Although cisplatin treatment clearly radiosensitized the
      lung tumour cells, CPEC treatment did not. Cisplatin-induced radiosensitization
      was also not enhanced by CPEC.

PMID- 22966340
TI  - Aloe-emodin, an anthraquinone, in vitro inhibits proliferation and induces
      apoptosis in human colon carcinoma cells.
AB  - The present study aimed to investigate the anticancer effect of aloe-emodin, an
      anthraquinone compound present in the leaves of Aloe vera, on two human colon
      carcinoma cell lines, DLD-1 and WiDr. Colon carcinoma cells were treated with
      various concentrations of aloe-emodin for different durations. Cell viability was
      measured by sodium 3'-[1-(phenylamino-carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6
      nitro) benzene-sulfonic acid hydrate assay. DNA fragmentation was analyzed by
      agarose gel electrophoresis. Nuclear shrinkage was visualized by Hoechst 33258
      staining. Western blotting was used to indicate the release of apoptosis-inducing
      factor and cytochrome c from mitochondria and the phosphorylation of Bid. Caspase
      3 and casein kinase II activities were measured by the respective assays. Cell
      viability analyses showed that aloe-emodin induced cell death in a dose- and time
      dependent manner. Notably, the WiDr cells were more sensitive to aloe-emodin than
      the DLD-1 cells. Aloe-emodin caused the release of apoptosis-inducing factor and
      cytochrome c from mitochondria, followed by activation of caspase-3 leading to
      DNA fragmentation, nuclear shrinkage and apoptosis. In addition, exposure of
      colon carcinoma cells to aloe-emodin suppressed the casein kinase II activity in
      a time-dependent manner and was accompanied by a reduced phosphorylation of Bid,
      a downstream substrate of casein kinase II and a pro-apoptotic molecule. These
      findings showed that the inhibition of casein kinase II activity, the release of
      apoptosis-inducing factor and cytochrome c, and the caspase-3 activation are
      involved in aloe-emodin-mediated apoptosis in colon carcinoma cells.

PMID- 22966341
TI  - Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in
      Chilean individuals.
AB  - Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire
      carcinogenicity following their activation by xenobiotic-metabolizing enzymes to
      highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to
      the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible
      for its detoxification. CYP1A1 and GSTM1 polymorphisms were evaluated in 124
      Chilean healthy controls and 48 oral cancer patients through PCR-based
      restriction fragment length polymorphism. In the healthy controls, frequencies of
      the CYP1A1 variant alleles for m1 (CYP1A1(*)2A) and the GSTM1null genotype were
      found to be 0.25 and 0.19, respectively. In the oral cancer patients, these
      frequencies were 0.33 and 0.50, respectively. Thus, the GSTM1 and m1 rare alleles
      were significantly more frequent in the oral cancer patients compared to the
      controls. The estimated relative risk for oral cancer associated with the single
      genotype CYP1A1 or GSTM1 was 2.08 for wt/m1, 1.04 for m1/m1 and 4.16 for the
      GSTM1null genotype. For smokers, the estimated relative risk (adjusted by age and
      gender) was higher in the individuals carrying the m1 allele of CYP1A1 [wt/m1:
      odds ratio (OR)=5.68, P=0.0080; m1/m1: OR=7.77, P=0.0420] or GSTM1null genotype
      (OR=20.81, P<0.0001). Combined genotypes CYP1A1 and GSTM1 increased the risk
      significantly (wt/m1/GSTM1null: OR=19.14, P=0.0030; m1/m1/GSTM1null: OR=21.39,
      P=0.0130). Taken together, these findings suggest that Chilean individuals
      carrying single or combined GSTM1 and CYP1A1 polymorphisms may be more
      susceptible to oral cancer induced by environmental tobacco smoking.

PMID- 22966342
TI  - Molecular identification of Helicobacter DNA in human gastric adenocarcinoma
      tissues using Helicobacter species-specific 16S rRNA PCR amplification and
      pyrosequencing analysis.
AB  - Helicobacter pylori (H. pylori) is a microaerophilic gram-negative bacterium
      known to be associated with chronic gastritis, peptic ulcer and gastric
      adenocarcinoma. In the present study, the presence of Helicobacter DNA was
      investigated using a Helicobacter species-specific 16S rRNA PCR amplification and
      pyrosequencing analysis in 51 resected gastric adenocarcinomas. DNA was extracted
      from paraffin-embedded tissues of resected gastric adenocarcinomas. PCR primers
      were designed to amplify the 133-bp PCR fragment in highly conserved regions of
      the 16S rRNA gene. The sequence of the PCR products was analyzed using a PSQ 96
      system with SQA software. The pyrosequencing analysis of 16S rRNA showed that H.
      pylori was present in 47 (92.2%) of the 51 gastric adenocarcinomas. In the 4 H.
      pylori-negative cases, Helicobacter cinaedi (2 cases), Helicobacter mustelae (1
      case) and Campylobacter hyointestinalis (1 case) were detected. Pyrosequencing
      technology was useful in the identification and differentiation of H. pylori from
      other species by analyzing the gene encoding 16S rRNA. Gastric adenocarcinoma
      tissues contain bacteria, and the majority are H. pylori. Helicobacter cinaedi,
      Helicobacter mustelae and Campylobacter hyointestinalis rarely occur. The roles
      of these organisms in the pathogenesis of gastric adenocarcinoma remain unclear.

PMID- 22966343
TI  - Simultaneous detection of expression and gene mutations of HER2/neu in Chinese
      patients with gastric cancer.
AB  - HER2/neu is one of the few identified oncogenes in tumorigenesis. Attention has
      been focused on the potential effect of HER2/neu mutations in the tyrosine kinase
      domain on carcinoma-targeted therapy. However, data concerning HER2/neu mutations
      in Chinese patients with gastric cancer (GC) are limited. This study aimed to
      detect the expression and somatic mutations of HER2/neu in Chinese patients with
      GC. Immunohistochemical staining for HER2/neu was performed on 72 formalin-fixed,
      paraffin-embedded specimens of GC (40 intestinal and 32 diffuse type). The
      correlation between the overexpression of HER2/neu and clinicopathological
      parameters was statistically analyzed. Somatic mutations in the tyrosine kinase
      domain of HER2/neu in the 72 patients were detected by direct sequencing. In the
      GC group, overexpression of HER2/neu was detected in 13 of the 72 GC patients and
      in 4 of the 72 adjacent tissues in the non-tumorous group (18.1 vs. 5.6%,
      P<0.05). Furthermore, the intestinal type of GC exhibited a higher rate of
      HER2/neu overexpression than the diffuse type (29.7 vs. 5.7%, P<0.05). The rate
      of HER2/neu overexpression in stage III-IV (TNM stage) GC cases was significantly
      higher than that in stage I-II (28.2 vs. 6.6%, P<0.05). HER2/neu overexpression
      correlated with a significantly less favorable patient survival (P=0.046). No
      somatic mutations in the tyrosine kinase domain of HER2/neu were detected in
      tumor tissues or the corresponding non-tumorous ones in the specimens obtained
      from the 72 Chinese GC patients. Results suggest that overexpression of HER2/neu
      is a frequent molecular event strongly associated with a poor patient prognosis,
      whereas the incidence of somatic mutations of the HER2/neu kinase domain is more
      likely a low-frequency event in Chinese GC patients.

PMID- 22966344
TI  - MicroRNA-mediated regulation of pancreatic cancer cell proliferation.
AB  - MicroRNAs (miRNAs) comprising 19-25 nucleotides are highly conserved small non
      coding RNAs which regulate normal gene expression during development, cell
      proliferation and apoptosis by targeting mRNAs of protein-coding genes at the
      post-transcriptional level. Prevalent studies suggest that some human miRNAs,
      such as miRNA-16, are deregulated in human cancer and behave as tumor
      suppressors. The overall objective of our investigation was to assess whether
      miRNA-16 (miR-16) is involved in the regulation of critical genes, such as BCL2,
      that control the sensitivity of pancreatic cancer cells to apoptosis. This study
      showed that the ectopic overexpression of miR-16 may be therapeutically
      beneficial as is evidenced by impaired cell survival with concomitant attenuation
      of anti-apoptotic protein Bcl-2. Moreover, the luciferase reporter assay
      suggested that miR-16 post-transcriptionally regulates Bcl-2 expression in
      pancreatic cancer cells through the target sites of the 3' untranslated region of
      this gene.

PMID- 22966345
TI  - Retrospective analysis of Japanese patients with relapse or refractory small-cell
      lung cancer treated with amrubicin hydrochloride.
AB  - Amrubicin (AMR) is one of the most active chemotherapeutic agents for small-cell
      lung cancer (SCLC). Previous phase II studies reported on its effectiveness and
      severe hematological toxicities. However, AMR has yet to be approved outside
      Japan. Subsequently, no extensive evidence of its effects exist. Between January
      2004 and October 2009, 69 patients received AMR for relapsed SCLC at our
      hospital. We reviewed these patients, and analyzed the efficacy and hematological
      toxicities of AMR. There were 27 sensitive relapses (S) and 42 refractory
      relapses (R). Patients received platinum agents, and 43 and 71% of the patients
      received etoposide and irinotecan, respectively. The median number of treatment
      cycles was 3 (range 1-14), and the response rate was 51% (70% in the S and 38% in
      the R cases, respectively). In patients administered with AMR as second-line
      therapy, the response rate was 55% and as third-line therapy, 39%. Median
      progression-free survival time was 3.2 months in the S and 1.9 months in the R
      patients (p=0.1071). Median survival time from the start of AMR was 6.2 months in
      the S and 4.8 months in the R cases (p=0.0045). The frequency of grade >=3
      hematological toxicities was leukopenia (41%), neutropenia (51%), anemia (14%),
      thrombocytopenia (17%) and febrile neutropenia (12%). No treatment-related death
      was observed. Although hematological toxicities, particularly neutropenia, were
      severe, AMR showed excellent anti-tumor activity, not only in the S, but also in
      the R cases, as shown in previous phase II studies. These results warrant further
      evaluation of AMR in the second-line setting, and also in the first-line setting
      in both limited- and extensive-stage disease. We conducted a phase II study to
      assess the efficacy of consolidation chemotherapy with AMR after standard
      chemoradiation in limited-stage SCLC.

PMID- 22966346
TI  - Advances in the research on lymphangiogenesis in carcinoma tissues (Review).
AB  - Metastatic spread of tumors is an important prognostic factor for cancer
      patients. The effect of angiogenesis on cancer cell proliferation and metastatic
      spread has been confirmed. However, less attention has been focused on research
      involving tumor lymphangiogenesis as opposed to research on tumor angiogenesis,
      due to the lack of specific markers for lymphatic vessel endothelial cells
      (LVECs). Recently, the improvement of isolation techniques for LVECs and the
      discovery of specific LVEC markers such as vascular endothelial growth factor
      receptor-3 (VEGFR-3), podoplanin, lymphatic vessel endothelial hyaluronan
      receptor-1 (LYVE-1) and Prox1 have led to advances in research involving
      lymphangiogenesis in carcinoma tissues. New lymphatic vessels in tumor tissues
      may originate from bone marrow endothelial progenitor cells, directly from the
      preexisting lymphatic vessels, and even by cell transformation. Peritumoral
      lymphatic vessels play a more important role in the process of tumor metastasis
      by providing more channels for lymphatic invasion and metastatic spread. The
      molecular mechanism of tumor lymphangiogenesis is complicated, and numerous
      factors such as VEGF-A, platelet-derived growth factors (PDGFs), hepatocyte
      growth factor (HGF), fibroblast growth factor-2 (FGF-2), and angiopoietins (Ang)
      are directly or indirectly involved in the process. However, it has been
      demonstrated that the VEGF-C/VEGF-D/VEGFR-3 signaling pathways are the most
      important mechanism underlying tumor lymphangiogenesis.

PMID- 22966347
TI  - Factors that influence the incidence of breast cancer in Arica, Chile (Review).
AB  - Breast cancer is a common disease estimated to occur in 1 in 9 women over their
      lifetime. Epidemiological research has identified a number of risk factors for
      breast cancer. Racial and ethnic differences in breast cancer mortality rates
      have been difficult to ascertain. The present review reports that there was an
      increase in the incidence of breast cancer in Arica, Chile, from 1997 to 2007,
      particularly in 2005, reaching 55.1% per 100,000 women, while the percentage
      decreased in 2006 and 2007. A greater percentage of breast cancer was found in
      individuals between 46 and 65 years of age when the population was distributed by
      age. The Indian population, Aymara, had only a 13.9% incidence of the disease.
      The incidence for breast cancer for patients with no family background reached
      approximately 88%, with or without Indian ethnicity, and 98.4% of these women did
      not have prior hormonal therapy. When the stage of the disease and the number of
      pregnancies were considered, results showed that there was an increase in the
      progression of the disease from stage I to stage III in women that had 1-3
      pregnancies. Results also showed that 20.9 and 33.2% who received prior tamoxifen
      treatment were in stages I and IIA, respectively. The breast cancer incidence
      reached 42.4% when patients had a sister with the disease. It can be concluded
      that important differences in the risk factors of breast cancer should be
      identified in the future for a comparison with other biological factors, such as
      genetic and molecular factors. This may provide greater insight into breast
      cancer aetiology in different populations.

PMID- 22966348
TI  - Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions
      with iron accumulation in female A/J mice.
AB  - It is crucial to develop therapeutic approaches for malignant mesothelioma, as
      well as to obtain information involving the possible mechanism involved in the
      development of mesothelioma. Subsequently, thoracotomy was performed to infuse
      test particles directly into the thoracic cavity of A/J mice. Fiber-shaped
      particles of potassium octatitanate (TISMO) and granular-shaped micro- and nano
      size order particles of titanium dioxide (TiO(2)) were employed (1.5 mg in 0.2 ml
      saline/mouse). The experiment was terminated after 21 weeks to assess responses.
      Only the fiber-shaped TISMO, morphologically similar to asbestos, induced a
      severe reaction of the pleura. A number of TISMO fibers were observed in the
      alveoli, indicating penetration through the pleura. Following Berlin blue
      staining, positive spots were observed around the TISMO fibers, indicative of
      iron. These positive spots corresponded with cells that immunostained positively
      for calretinin, a marker of mesothelial cells. Similar observations were reported
      for asbestos-induced mesothelioma. The present study showed that only fiber
      shaped TISMO induced severe reactions of the mesothelium in the pleura, and these
      involved iron accumulation derived from endogenous sources. The results indicate
      that the risk of mesothelial cell reaction does not depend on particle size, but
      may depend on shape.

PMID- 22966349
TI  - Diffuse gliomas in an adolescent with multiple enchondromatosis (Ollier's
      disease).
AB  - Ollier's disease is characterized by the hamartomatous proliferation of cartilage
      cells, producing masses termed chondromas. A patient presented with Ollier's
      disease which was found to be associated with diffuse gliomas. Investigating this
      disease is crucial as there is a high risk of sarcomatous transformation of the
      skeletal lesions as well as an increased risk of developing extra-osseous
      malignancies.

PMID- 22966350
TI  - Relationship among human papillomavirus infection, p16(INK4a), p53 and NF-kappaB
      activation in penile cancer from northern Thailand.
AB  - Human papillomavirus (HPV) E6 and E7 oncoproteins are essential factors for HPV
      oncogenesis. These E6 and E7 gene products play a central role in the induction
      of malignant transformation by interacting with several cellular regulatory
      proteins such as p16(INK4a), p53 and nuclear factor kappaB (NF-kappaB). In the
      present study, conducted in northern Thailand, HPV-DNA was detected in penile
      cancer cases using an in situ hybridization procedure and p16(INK4a), p53 and NF
      kappaB were detected by immunohistochemistry. Using the cell cycle regulatory
      proteins p16(INK4a) (61.5%) and p53 (71.8%), it was found that of the 51 cases,
      39 (76.5%) were HPV-DNA-positive in penile cancer. On the other hand, 25%
      p16(INK4a) and 75% p53, respectively, were found in HPV-negative cases.
      Prevalence of HPV infection (76.5%) was shown in penile cancer cases in northern
      Thailand. No difference was found between HPV-positive and HPV-negative cases
      with respect to the presence of the cell cycle regulatory protein p53. On the
      other hand, p16(INK4a) was found to be different between HPV-positive and HPV
      negative cases. Inactivation of tumor suppressor genes, such as p16(INK4a) and
      p53, to genetic instability, cell immortalization, accumulation of mutations and
      cancer formation, with or without HPV and irrespective of HPV infection, is
      therefore suggested. Of the 39 HPV-positive cases, 35 (89.7%) were NF-kappaB
      positive in the nucleus, 29 (74.4%) in the cytoplasm and 37 (94.9%) in the
      nucleus and/or cytoplasm. NF-kappaB was detected in 4 (33.3%) of the 12 HPV
      negative cases. Therefore, we propose that penile cancer cases with HPV infection
      are more likely to activate NF-kappaB than those without HPV infection.

PMID- 22966351
TI  - Unique intense uptake demonstrated by (18)F-FDG positron emission
      tomography/computed tomography in primary pancreatic lymphoma: A case report.
AB  - Patients with primary pancreatic lymphoma (PPL), which is rare, require a
      different therapeutic approach and have a better prognosis than those with
      pancreatic cancer. However, conventional imaging modalities alone are not able to
      differentiate between pancreatic cancer and other rare tumors such as PPL,
      although the accurate diagnosis of PPL is crucial. The development of new
      modalities such as F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission
      tomography combined with computed tomography (PET/CT) contributes to the
      evaluation of lymphoma staging. However, few reports are currently available
      regarding PET/CT findings in PPL. In this study, a 56-year old man with PPL was
      examined using FDG PET/CT imaging, which showed the unique intense uptake of FDG
      in the pancreas with atypical findings of malignancy in the CT scan and magnetic
      resonance images.

PMID- 22966353
TI  - Wilms' tumor 1 gene (WT1) is overexpressed and provides an oncogenic function in
      pediatric nephroblastomas harboring the wild-type WT1.
AB  - Wilms' tumor 1 gene (WT1) is known to be a tumor suppressor gene in the subset of
      nephroblastomas that harbors WT1 mutations. However, its role in nephroblastomas
      without mutations remains unclear. This study aimed to evaluate the expression of
      WT1 and its potential oncogenic role in pediatric nephroblastoma with wild-type
      WT1. A total of 24 nephroblastomas were studied for WT1 mRNA expression by
      quantitative reverse-transcription polymerase chain reaction. The expression
      levels were compared between nephro-blastomas with and without WT1 mutations, as
      well as to normal kidney tissue, other pediatric renal tumors and neuroblastomas.
      Immunohistochemistry was used to evaluate expression patterns at the tissue
      level. Post-transcriptional inhibition of WT1 was performed in primary cultures
      of wild-type nephroblastoma using WT1 siRNA. The average WT1 expression level in
      nephroblastoma tissue was significantly higher than that in normal kidney tissue
      and neuroblastomas. Expression at the mRNA level was not different between
      nephroblastomas with WT1 mutations (4 cases) and those with wild-type WT1 (20
      cases). However, while WT1 immunoreactivity was positive in all of the
      nephroblastoma components in the tumors with wild-type WT1, the protein
      expression was weaker and limited to stromal components in the tumors with
      mutated WT1, where it co-localized with beta-catenin nuclear accumulation. The
      post-transcriptional inhibition of WT1 resulted in growth retardation and a
      significantly increased apoptotic fraction. Our study found overexpression of the
      WT1 gene in pediatric nephroblastomas with wild-type WT1. Moreover, the study
      suggests an oncogenic role of WT1 in this tumor subset.

PMID- 22966352
TI  - p53R2 expression as a prognostic biomarker in early stage non-small cell lung
      cancer.
AB  - p53R2 is a small subunit of ribonucleotide reductase (RR) which has 80% homology
      to hRRM2 and metastasis-suppressing potential. Previous reports suggested that
      the expression of p53R2 is used as a prognostic factor and chemotherapy response
      indicator in several types of cancer. This study aimed to elucidate the
      association of p53R2 expression and the clinicopathological characteristics of
      early stage non-small cell lung cancer (NSCLC). Immunohistochemistry was
      conducted on a tissue array including 92 early stage NSCLC samples. Correlations
      between p53R2 and clinicopathological factors, recurrence/metastasis and outcomes
      were analyzed. The analyses showed that there was no correlation between p53R2
      expression and the clinicopathological factors. Among disease-free patients
      during follow-up, patients with p53R2(+) had a better outcome than those with
      p53R2(-) (P=0.022). By using Cox multivariate regression analysis, p53R2 (risk
      factor 3.801; 95% CI 1.004-9.454; P=0.044) served as a prognostic biomarker in
      the prediction of the survival rate for NSCLC patients. Detection of the RR
      subunit p53R2 may therefore be a useful prognostic marker in early stage NSCLC.

PMID- 22966354
TI  - Maspin protein expression correlates with tumor progression in non-muscle
      invasive bladder cancer.
AB  - Maspin is a 42-kDa protein that belongs to the family of serine protease
      inhibitors. It is involved in various physiological processes. In cancer tissue,
      Maspin was found to influence angiogenesis, tumor growth, metastasis and the
      prognosis of tumor patients. This study was performed to analyze the involvement
      of Maspin in transitional cell carcinoma of the bladder as well as its prognostic
      impact in a large patient cohort. Specimens from 162 non-muscle invasive bladder
      cancer patients (pTa, 91; pT1, 71) treated by transurethral resection with a
      minimum 3-year follow-up (median 58.5 months) were included in the present
      investigation. Tissue microarrays were constructed, and the specimens were
      immunohistochemically stained for Maspin protein expression. Each tissue specimen
      was assessed on a staining scale ranging from 0 (no staining) to 300 (strong
      staining) and correlated with various clinicopathological parameters. Maspin
      protein expression predicted progression with a sensitivity of 95% and a
      specificity of 70% (p<0.001). In predicting recurrence, Maspin staining showed
      52% sensitivity and 67% specificity (p<0.05). Kaplan-Meier analyses were
      performed, and a low Maspin protein expression was correlated with a higher
      incidence of tumor progression (p<0.0001). However, expression levels of Maspin
      protein did not distinguish between pTa and pT1 specimens. Multivariate analyses
      indicated Maspin expression as an independent factor for predicting progression
      (p<0.0001) and recurrence (p<0.05). The present results suggest that the Maspin
      protein expression is an independent prognostic indicator for predicting
      recurrence and progression to muscle invasive disease. This study further
      emphasizes a possible clinical role of this novel tumor suppressor gene in
      transitional cell carcinoma of the bladder.

PMID- 22966355
TI  - Modified grading system for clinical outcome of intracranial non-germinomatous
      malignant germ cell tumors.
AB  - This study investigated the clinical outcome of intracranial non-germinomatous
      malignant germ cell tumors (NGMGCTs). All histologically proven cases of NGMGCTs
      treated in Shanghai Huashan Hospital, Fudan University were reviewed. A total of
      39 cases were analyzed. There were 15 mixed germ cell tumors, 15 immature
      teratomas, 7 embryonal carcinomas and 2 yolk sac tumors. Patients were treated
      surgically first, followed by radiotherapy and/or chemotherapy. Some patients
      also received gamma knife surgery. The common 5-year survival rate was 36.8%.
      According to Matsutani's grading system, the 5-year actuarial survival rate for
      patients in the intermediate and poor prognosis groups were 45.8 and 14.3%,
      respectively. Individual analysis of each type of tumor showed that the median
      survival time of embryonal carcinoma was 27 months, which is very close to that
      of the intermediate group (28 months). We therefore classified embryonal
      carcinoma into the intermediate group where the 5-year actuarial survival rate
      for patients in the new intermediate prognosis group was 42.6%. Further analysis
      of immature teratoma cases found that the 5-year survival rate of patients with
      immature teratoma who received gamma knife surgery is 100%. This rate exhibited a
      significant difference (P=0.0049) compared to that of patients who did not
      undergo gamma knife surgery. In conclusion, we consider surgery as the first
      choice of treatment although for different histologis, the type of the tumor
      should be treated separately.

PMID- 22966356
TI  - Nuclear factor-kappaB expression is predictive of overall survival in patients
      with cutaneous melanoma.
AB  - Nuclear factor (NF)- kappaB is one of the most important transcription factors
      that plays a crucial role in the regulation of a wide spectrum of genes involved
      in modulating the cell cycle, apoptosis, cell growth, angiogenesis, inflammation
      and the tissue invasiveness of highly malignant cells. NF-kappaB activity has
      been found to be constitutively elevated in a number of human tumors from either
      a haematological or solid origin, such as melanomas. In several studies, NF
      kappaB activation was shown to be an adverse prognostic factor, and in melanoma
      it was proposed as an event that promotes tumor progression. This study aimed to
      evaluate whether NF-kappaB activation in tumor tissues, assessed by the
      expression of the NF-kappaB p65 subunit, has an effect on the survival of
      melanoma patients. The expression of NF-kappaB was immunohistochemically
      investigated, and the correlation with survival was analyzed. Furthermore, the
      immunostaining for p53 and survivin was evaluated, and the relationship of these
      apoptotic and anti-apoptotic factors with NF-kappaB expression was analyzed.
      Kaplan-Meier analysis showed that patients with low levels of NF-kappaB in the
      nuclei of tumor cells had a significantly longer survival compared to those with
      high levels. Multivariate analysis confirmed the predictive value of nuclear NF
      kappaB, showing that its expression maintains significance after the model was
      adjusted using clinicopathological factors. The results demonstrate the
      correlation of NF-kappaB p65 nuclear staining with the disease-specific 5-year
      survival of melanoma patients and suggest that nuclear NF-kappaB p65 may be
      promising as an early independent prognostic factor in patients with primary
      cutaneous melanoma.

PMID- 22966357
TI  - Predictive value of Smac, VEGF and Ki-67 in rectal cancer treated with
      neoadjuvant therapy.
AB  - The present study aimed to identify whether second mitochondria-derived activator
      of caspase (Smac), vascular endothelial growth factor (VEGF) and proliferating
      cell nuclear antigen (Ki-67) expression in pre-treatment tumor biopsies are
      useful predictive markers of tumor response in patients with rectal cancer
      undergoing pre-operative chemoradiotherapy (CRT). Paraffin-embedded tissues
      obtained before and after therapy were evaluated by immunohistochemical staining
      for Smac, VEGF and Ki-67. The study evaluated the correlation of Smac, VEGF and
      Ki-67 immunoreactivity in tumor biopsies before treatment of tumor response to
      pre-operative CRT. Regarding Smac, patients with a favorable response to
      neoadjuvant CRT had higher pre-therapy levels (p=0.011). The level of Smac
      expression decreased after neoadjuvant therapy (p=0.044). However, VEGF
      expression was found to be negatively and significantly correlated with a
      favorable tumor response to neoadjuvant CRT (p=0.010). A transient increase in
      VEGF expression was detected in the resected specimens following neoadjuvant
      therapy (p=0.030). In addition, tumors with a low Ki-67 labeling index (Ki-67-LI)
      expression were found to be more sensitive to neoadjuvant therapy than those with
      a high expression of Ki-67-LI (p=0.034). In contrast to VEGF, the Ki-67
      expression level decreased after neoadjuvant therapy. Smac, VEGF and Ki-67
      expression levels, assessed immunohistochemically from pre-treatment tumor
      biopsies, may be useful predictive markers of rectal tumor response to pre
      operative CRT.

PMID- 22966358
TI  - Small-interfering RNA-mediated silencing of the MAPK p42 gene induces dual
      effects in HeLa cells.
AB  - The genesis and progression of cervical cancer involve the mutation or deviant
      expression of numerous genes, including the activation of oncogenes (Ha-ras, C
      myc, C-erbB2 and Bcl-2) and inactivation of tumor-suppressor genes (p53 and Rb).
      Previous studies showed that small-interfering RNAs (siRNAs) targeting the MAPK
      p42 gene partly inhibit proliferation and increase apoptosis in human cervical
      carcinoma HeLa cells. Results of a microarray analysis showed that MAPK p42 siRNA
      inhibited cell growth through the regulation of cell cycle control and apoptosis
      and induced interferon-like response in HeLa cells. In order to confirm the dual
      effects of MAPK p42 siRNA, we compared the roles of siRNA and U0126, an inhibitor
      of MAPK p42, in HeLa cells. Short 21-mer double-stranded/siRNAs were synthesized
      to target MAPK p42 mRNA in HeLa cells. The siRNAs were transfected into HeLa
      cells using Lipofectamine. The cells were treated with siRNA or U0126 at
      different concentrations for a period of 48 h. The biological effect of siRNA and
      U0126 on HeLa cells was measured by MTT and flow cytometry. MAPK1, NUP188, P38,
      STAT1, STAT2, PML and OAS1 were analyzed by real-time quantitative PCR. HeLa cell
      growth was inhibited by siRNA or U0126, and the effect of siRNA inhibition was
      greater than that of U0126. Cell cycle phases were different for siRNA or U0126,
      but HeLa cell growth was arrested at the S phase by siRNA and at G1 phase by
      U0126. A down-regulation in MAPK p42 expression by siRNA and up-regulation by
      U0126 were noted. The results of real-time quantitative PCR showed that P38 was
      up-regulated and NUP188 was down-regulated by siRNA in comparison with the
      control groups, and the results were consistent with those of U0126. Expression
      levels of STAT1, STAT2, PML and OAS1 induced by siRNA differed from those induced
      by U0126. siRNA-mediated silencing and deactivation induced by U0126 in MAPK p42
      led to growth inhibition in the HeLa cells. The effects of siRNA on HeLa cell
      growth were different from those of U0126. Dual effects of MAPK p42 siRNA-2 on
      HeLa cell growth were noted: one consisted of a specific effect induced by siRNA
      mediated p42 MAPK silencing and the other exhibited a non-specific interferon
      like response.

PMID- 22966359
TI  - Role and mechanism of hypoxia-inducible factor-1 in cell growth and apoptosis of
      breast cancer cell line MDA-MB-231.
AB  - The role of hypoxia-inducible factor-1 (HIF-1) in tumor development and
      progression is well-established but its effect on tumor growth remains
      controversial. The present study investigated the effect of HIF-1 on tumor growth
      using the estrogen receptor-negative breast cancer cell line, MDA-MB-231. Using
      Western blotting, we detected a higher level of HIF-1alpha protein in MDA-MB-231
      cells than in any other breast cancer cell lines analyzed, and this was
      accompanied by a more rapid growth pattern. Interruption of HIF-1alpha expression
      using small interference RNA (siRNA) significantly suppressed cell growth and
      increased apoptosis, but the cell cycle was not affected. Activated fragments
      with increased caspase 3 activity and a mobility shift of B cell lymphoma (Bcl-2)
      were also detected in cells treated with HIF-1alpha siRNA. HIF-1 allows breast
      cancer cells to grow under long-term serum deprivation by inactivation of the
      caspase cascade and thus inhibition of apoptosis. Blocking HIF-1alpha protein
      resulted in loss of Bcl-2 function, which may contribute to the activation of the
      caspase cascade.

PMID- 22966360
TI  - Effect of thalidomide and arsenic trioxide on the release of tumor necrosis
      factor-alpha and vascular endothelial growth factor from the KG-1a human acute
      myelogenous leukemia cell line.
AB  - Studies conducted in our lab have indicated that thalidomide cytotoxicity in the
      KG-1a human acute myelogenous leukemia (AML) cell line was enhanced by combining
      it with arsenic trioxide. The current investigation was conducted in order to
      evaluate the effect of thalidomide either alone or in combination with arsenic
      trioxide on the release of tumor necrosis factor-alpha (TNF-alpha) and vascular
      endothelial growth factor (VEGF) from this cell line in an attempt to clarify its
      possible cytotoxic mechanism(s). Human AML cell line KG-1a was used in this
      study. The cells were cultured for 48 h in the presence or absence of thalidomide
      (5 mg/l), and or arsenic trioxide (4 MUM). The levels of TNF-alpha and VEGF in
      the supernatant were determined by ELISA. Results obtained indicate that the
      levels of TNF-alpha in the supernatant of KG-1a cell cultures incubated with
      thalidomide, arsenic trioxide, or combination were statistically lower than those
      observed in the supernatant of control cells (2.89, 5.07, 4.15 and 16.88 pg/ml,
      respectively). However, the levels of VEGF in the supernatant of thalidomide
      treated cells were statistically higher than those in the supernatant of control
      cells (69.61 vs. 11.48 pg/l). Arsenic trioxide, whether alone or in combination
      with thalidomide, did not produce any statistically significant difference in the
      levels of VEGF as compared to the control or thalidomide-treated cell
      supernatant. These findings indicate that thalidomide and the arsenic trioxide
      inhibition of TNF-alpha production by KG-1a cells may play an important role in
      their cytotoxic effect.

PMID- 22966361
TI  - Examination of the clinical usefulness of TS-1 in locally recurrent breast
      cancer.
AB  - This study examined the therapeutic efficacy of TS-1 in the treatment of locally
      recurrent breast cancer. Between August 2006 and May 2009, 7 patients with local
      breast cancer recurrences were selected included in the study. The sites of
      recurrence were the cervical lymph nodes in 4 patients, the axillary lymph nodes
      in 2 and the thoracic wall in 1. Among the 7 patients, 6 were administered TS-1
      as first-line treatment and 1 was administered TS-1 as second-line treatment.
      Complete response (CR) was achieved in 2 patients, 1 achieved partial response, 2
      had stable disease (SD), 1 had long SD and 1 had progressive disease. The overall
      response rate was 43%, and the clinical benefit rate was 57%. A patient with
      recurrence of breast cancer in the thoracic wall 28 years after surgery also
      achieved CR following therapy. The only adverse event observed was a case of hand
      foot syndrome in 1 patient. No patients withdrew from treatment, and favorable
      compliance was achieved in the study. The results indicated that TS-1 has the
      potential to be one of the drugs for first-line treatment of locally recurrent
      breast cancer.

PMID- 22966362
TI  - Octreotide acetate enables the administration of chemoradiotherapy, including the
      oral anticancer drug S-1, in gastric cancer patients with malignant
      gastrointestinal obstruction.
AB  - Advanced gastric cancer frequently results in the inability to ingest food or
      drink orally, a condition called malignant gastrointestinal obstruction (MGO).
      MGO is clinically defined as a gastrointestinal outlet obstruction caused by a
      large tumor, or malignant bowel obstruction with peritoneal dissemination. MGO
      impacts the quality of life by interfering with oral intake and by causing
      gastrointestinal symptoms, such as nausea, vomiting and abdominal pain.
      Octreotide acetate (OA) is an analogue of somatostatin which has been
      increasingly used to relieve gastrointestinal symptoms since it decreases the
      secretion of digestive juices and increases the absorption of water and
      electrolytes. In Japan, the oral anticancer drug S-1 was recently adopted as a
      key chemotherapeutic agent in advanced gastric cancer; however, its oral
      formulation precludes its utility in the MGO setting. This is a pilot study of
      chemoradiotherapy plus OA in gastric cancer with MGO. Patients were initially
      treated with OA to control gastrointestinal symptoms. Following resolution of
      their symptoms, the patients received chemotherapy with S-1 plus low-dose
      cisplatin and radiation. Irradiation was targeted at the primary tumor and
      surrounding lesions, including the lymph nodes. Grade 4 toxicity was observed in
      only 1 patient, and no treatment-related deaths were noted. After treatment, 3
      patients achieved a partial response and 4 achieved stable disease. Of the 9
      patients, 8 were able to tolerate solid food orally and were discharged. The
      outcomes of these cases suggest that OA is a useful adjunctive therapy that
      enables advanced gastric cancer patients with MGO to receive S-1-containing
      chemotherapy.

PMID- 22966363
TI  - Role of conventional salvage multiple-drug chemotherapy in relapsed and
      refractory aggressive non-Hodgkin lymphomas.
AB  - Autologous stem cell transplantation is the standard care for patients with
      relapsed or refractory aggressive non-Hodgkin lymphomas. Of the patients who are
      sensitive to second-line chemotherapy, approximately 40-50% are likely to be
      cured using this approach. The optimal salvage regimen for pre-transplant
      debulking is controversial and these second-line chemotherapies are particularly
      important for patients who cannot undergo transplantation for various reasons
      including age, comorbidity and insufficient stem cell collection. Numerous
      reports regarding this topic are available. This study evaluated reports
      published in the last 5 years, focusing on conventional multiple-drug second-line
      chemotherapies (with or without rituximab), and disregarding single-agent
      investigational phase-II trials. Results are encouraging, particularly when
      considering that the more recent and less toxic combinations appear to be
      equivalent to or even more favourable than previous, more aggressive approaches.
      Previous results obtained using a combination of mitoxantrone, carboplatin,
      cytarabine and methylprednisolone, are further updated and included in this
      study. In conclusion, the most effective conventional chemotherapy currently
      available for patients with relapsed or refractory non-Hodgkin lymphomas obtains
      complete remission rates of up to 50-70%; the achievement of a complete remission
      is the most important factor associated with a better outcome. Although the
      addition of rituximab is beneficial and safe, it is more effective in patients
      who have previously not been exposed to this monoclonal antibody. The addition of
      cycles of salvage chemotherapy to those strictly required for mobilization of
      peripheral blood stem cells ultimately improves the response rate.

PMID- 22966364
TI  - MicroRNA-34b has an oncogenic role in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is a common malignancy and one of the
      more difficult diseases to diagnose in Japan due to its poor prognosis. MicroRNAs
      are small non-coding RNAs of 21-23 nucleotides that regulate gene expression.
      MicroRNA-34b (miR-34b) has been reported to be overexpressed in various types of
      cancer. However, its role in ESCC has yet to be extensively studied. The present
      study investigated the expression of miR-34b in 88 ESCC patients. The miR-34b
      expression in ESCC was significantly higher than that in the corresponding normal
      esophageal mucosa. It was more highly expressed in tumors with more advanced
      stages. However, its expression did not correlate with the p53 status.
      Transfection of anti-miR-34b to the ESCC cells suppressed cell growth in vitro.
      These results suggest an oncogenic role of miR in ESCC.

PMID- 22966365
TI  - Profiling of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases proteins in bladder urothelial carcinoma.
AB  - We investigated the matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinase (TIMPs) proteins in transitional cell carcinoma (TCC) cell
      lines and surgical specimens of the bladder neoplasm. The expression level was
      correlated to the degree of cellular differentiation and invasiveness of bladder
      cancer. Panels of six TCC cell lines with different degrees of differentiation
      were tested with monoclonal antibodies (mAbs) to MMP-1, MMP-2, MMP-3, MMP-9a, MMP
      9b, TIMP-1 and TIMP-2 by immunocytochemistry. Gelatin zymography was also
      conducted on the cell lines for MMP-2 and -9. In addition, immunohistochemistry
      with the mAbs to MMP and TIM molecules was performed on 30 TCC specimens. We
      found that TCC cell lines were stained positively for MMP-1 (6/6), weakly for MMP
      9a (2/6), MMP9b (5/6) and TIMP-1 (3/6), and negatively for MMP-2 (3/6) and MMP-3
      (3/6). Zymographic analysis of the cell lines showed a high level of MMP2 in the
      MGH-U4 cell line. In bladder cancer surgical specimens, all specimens were
      positive for MMP1 (30/30), 19 were positive for MMP-2 (63.3%), 21 positive for
      MMP-9a (70%) and 15 positive for MMP-9b (50%). The expression of MMP-2 was found
      to be positively correlated with higher-grade tumors (p=0.036) and the expression
      of MMP-9a and -9b was found to be positively correlated with tumor stage (p=0.012
      and 0.023, respectively). However, the expression of MMP-1, MMP-3, TIMP-1 and
      TIMP-2 was not correlated with either tumor staging or grading. In conclusion,
      the expression of MMP-2 and -9 was correlated with high-grade or high-stage
      bladder tumors, respectively. However, this correlation was not observed with TCC
      cell lines in which high- and low-grade tumors are included. Immunohistochemical
      results on tumor lesions may have more clinical relevance, since in a given tumor
      microenvironment the interaction among tumor cells in situ and tumor-associated
      cells, such as neutrophils, macrophages, lymphocytes and endothelial cells, as
      well as environmental factors (hypoxia and pH), cytokines and growth factors
      released by these cells may be required for TCC to express selective MMPs and
      TIMPs. The selective expression of these molecules then regulates tumor
      progression.

PMID- 22966366
TI  - Expression of hypoxia-inducible protein 2 in renal cell carcinoma: A promising
      candidate for molecular targeting therapy.
AB  - This study investigated the expression of hypoxia-inducible protein 2 (HIG2), a
      novel renal cell carcinoma (RCC)-associated molecule and an essential growth
      factor for RCC, in kidneys to elucidate its clinical significance in RCC. An
      immunohistochemical study of HIG2 was conducted in 93 surgical samples of RCC
      tissues and 10 samples of normal kidney tissues obtained after nephrectomies for
      localized RCC. HIG2 expression was also correlated with clinicopathological
      characteristics and survival. Only faint or weak immunostaining for HIG2 was
      observed in normal kidney samples. HIG2 expression was found in 86% of RCC
      tissues (80/93). When analyzed by histological type, positive staining for HIG2
      was detected in all papillary (7/7), chromophobe (1/1) and cyst-associated (3/3)
      RCC. In contrast, the HIG2 expression was observed in 85% of clear cell (68/80)
      and 50% of spindle cell (1/2) RCC. Labeling indices were 74.1, 45.4, 39, 24.8 and
      12.1% in papillary, spindle, clear cell, cyst-associated and chromophobe RCC,
      respectively. A significant increase in HIG2 expression was noted in RCC tissues
      obtained from patients with high stage RCC, lymph node metastasis and high
      nuclear grade (p<0.001, p<0.02 and p<0.006, respectively). RCC patients with a
      negative HIG2 staining had prolonged 5-year cancer-specific survival. In
      conclusion, HIG2 expression was extensively observed in RCC tissues and was
      higher in advanced RCC, suggesting that HIG2 is a candidate for the development
      of molecular targeting therapy.

PMID- 22966367
TI  - Prognostic significance of Minichromosome maintenance protein 7 and Geminin
      expression in patients with 109 soft tissue sarcomas.
AB  - Minichromosome maintenance complex (MCM2-7) and Geminin are important in the
      prevention of DNA re-replication in the cell cycle, and are also prognostic
      markers for numerous human malignancies. The present study examined
      Minichromosome maintenance protein 7 (MCM7) and Geminin expression in human soft
      tissue sarcomas (STSs) to clarify their correlation to the clinicopathological
      factors. Immunohistochemistry was performed to detect the expression of MCM7,
      Geminin and Ki-67 on paraffin-embedded sections of 109 STSs. Labeling indices
      (LIs) of the molecules were evaluated in the tumors. Higher LIs of MCM7, Geminin
      and Ki-67 were significantly correlated with distant metastasis (P<0.01),
      histological grade (P<0.01) and poor prognosis (P<0.01), respectively. LIs of
      MCM7 and Geminin were significantly correlated with Ki-67 LIs, (MCM7/Ki-67:
      rs=0.745, P<0.01 and Geminin/Ki-67: rs=0.604, P<0.01). Multivariate analyses
      showed that the higher LIs of Geminin, but not MCM7 and Ki-67, were shown to be
      an independent factor of poorer prognosis (relative risk 2.72, P=0.013). The
      immunohistochemical expression of MCM7 and Geminin may be novel and useful
      markers for evaluating the prognosis in patients with human STS.

PMID- 22966368
TI  - Detection of P53 mutations in different cancer types is improved by cDNA
      sequencing.
AB  - Recently published data show discrepancies between P53 cDNA and DNA sequencing
      results in glioblastoma, colorectal cancer and pleomorphic xanthoastrocytoma. We
      hypothesized that similar discrepancies are observed in other types of human
      cancers. Using DNA and cDNA direct sequencing, we analyzed 40 cases of invasive
      breast duct carcinoma, 23 cases of acute myeloblastic leukaemia, 12 cases of
      astrocytoma and 40 cases of soft tissue sarcoma for P53 mutations. Additionally,
      we used real-time quantitative PCR to estimate the normalized relative P53
      expression. In the comparative study, the P53 mutation was detected more
      frequently when using cDNA sequencing than DNA sequencing in all of the cancer
      types. Furthermore, several samples presented missense P53 mutations, with
      visible wild-type nucleotide on the DNA sequence. In contrast, elimination of the
      wild-type allele or selective overproduction of the mutated allele was observed
      on the cDNA sequence. P53 expression was not significantly different between the
      cases with or without P53 mutations. These results indicate that cDNA sequencing
      improves the detection of P53 mutations in these cancers. We suggest that the
      true incidence of P53 mutations in these cancers is underestimated at the DNA
      level, and evaluation of the alteration should be carried out using cDNA
      analysis.

PMID- 22966369
TI  - Serous microcystic adenoma of the pancreatic head: Report of two cases and review
      of the literature.
AB  - Serous microcystic adenomas (SMAs), also known as glycogen-rich cystadenomas, are
      uncommon exocrine tumors mainly involved in the body and tail of the pancreas. In
      this study, we report two SMA cases of the pancreatic head. In case 1, a 47-year
      old woman was referred to our hospital for abdominal bloating and back pain; in
      case 2, a pancreatic space-occupying lesion was incidentally discovered in an
      asymptomatic 71-year-old female during an ultrasound. In both cases, a computer
      tomography scan showed well-demarcated and multilocular cysts in the head of the
      pancreas, and a central scar and calcifications were noted in case 1. During the
      exploratory laparotomies, the multiple cystic masses were found in the pancreatic
      head. A segmental resection of the pancreas and pancreatic jejunal anastomosis
      were performed. Histologically, the tumors were composed of tiny cysts that were
      filled with clear fluid and lined by a single layer of cuboidal cells with round,
      centrally located nuclei and clear cytoplasm, without cellular atypia.
      Immunohistochemical studies showed that the neoplastic cells were positive for
      cytokeratin 7 and vimentin but negative for synaptophysin and cytokeratin 20. A
      postoperative follow-up indicated no recurrence in the patients. We reviewed the
      literature regarding the etiology, clinical presentation, imaging
      characteristics, features and management of this lesion.

PMID- 22966370
TI  - Activating BRAF gene mutations are uncommon in hormone refractory prostate cancer
      in Caucasian patients.
AB  - Activating mutations in the cytosolic serine/threonine kinase, BRAF, have been
      reported in a variety of neoplasms. BRAF activation may contribute to tumor
      growth via activation of the MAP/ERK kinase pathway, and BRAF represents a
      possible therapeutic target. Activating BRAF mutations were recently reported in
      approximately 10% of prostate cancer cases in Asian patients. In the present
      study, 43 hormone refractory prostate cancers were analyzed for BRAF mutations in
      order to determine whether anti-BRAF therapy is a suitable approach for advanced
      prostate cancer patients. In all of the studied tumors, BRAF exons 11 and 15 were
      PCR-amplified and sequenced, including the backward and forward sequences. BRAF
      mutations were noted only in the positive control tissues, but were not found in
      any of the 43 analyzed prostate cancers. We conclude that BRAF mutations occur
      only rarely in prostate cancers in Caucasian patients and are not associated with
      tumor progression. The application of anti-BRAF therapies may therefore not be
      beneficial for prostate cancer.

PMID- 22966371
TI  - Rituximab purging and maintenance therapy combined with autologous stem cell
      transplantation in patients with diffuse large B-cell lymphoma.
AB  - The aim of this prospective, single-arm study was to test the efficacy and
      tolerability of autologous stem cell transplantation (auto-SCT) combined with in
      vivo rituximab purging and post-transplant rituximab maintenance therapy in
      patients with diffuse large B-cell lymphoma (DLBCL). This study included 12 DLBCL
      patients aged 18-65 years with an International Prognostic Index >=2. The
      patients received 4-6 cycles of induction therapy consisting of rituximab plus
      cyclophosphamide, adriamycin, vincristine and prednisone followed by salvage
      therapy prior to stem cell mobilization. This regimen was followed by rituximab
      maintenance therapy (375 mg/m(2) every three months for two years). Prior to auto
      SCT, six patients (50%) achieved complete remission (CR) and six (50%) achieved
      unconfirmed complete remission (CRu). Three months after transplantation, 11
      patients (91.7%) achieved CR and one achieved CRu. After two cycles of rituximab
      maintenance therapy, all 12 patients achieved CR. Long-term CR was achieved by 10
      patients, while two experienced relapse at 14 and 20 months after the end of
      rituximab maintenance therapy. The median follow-up period was 44 months (range
      35-61). Disease-free survival was noted in 10 patients, while two experienced
      relapse. The three-year overall survival (OS) and progression-free survival (PFS)
      were 100 and 83%, respectively. Prolonged hypogammaglobulinemia occurred in two
      patients, although no increase in major infections was observed. Hepatitis B
      surface antigen was continuously negative in all 12 patients. Our results
      demonstrated that auto-SCT combined with in vivo rituximab purging and post
      transplant rituximab maintenance is safe and effective, and may extend OS and PFS
      in younger high-risk DLBCL patients.

PMID- 22966372
TI  - Plasma VEGF levels in breast cancer patients with and without metastases.
AB  - Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis since
      it stimulates the formation of new blood vessels. Basic fibroblast growth factor
      (bFGF) is related to the promotion of endothelial cells into tube-like
      structures, and it is therefore expected to promote angiogenesis with a greater
      potency than VEGF. VEGF and bFGF are considered to be biomarkers that predict
      treatment effectiveness. Elevated plasma VEGF and bFGF levels have been reported
      in a variety of different malignant tumors, and patients with metastatic disease
      have also been reported to present with higher serum VEGF and bFGF levels. Other
      studies have documented controversial results with respect to the prognostic and
      predictive value of the aforementioned biomarkers. This study aimed to determine
      the plasma VEGF and bFGF levels in breast cancer patients without metastatic
      disease compared with breast cancer patients with advanced metastatic disease.
      The study included 93 patients with breast cancer, 46 without recurrent disease
      (group A) and 47 with metastatic disease (group B), as well as 21 healthy
      individuals. The median age was 58 years (range 34-78) for group A and 59 years
      (range 37-75) for group B. All 93 patients underwent chemotherapy, adjuvant for
      group A, and adjuvant plus chemotherapy for group B patients with advanced
      disease. Plasma VEGF and bFGF levels were determined using a quantitative
      sandwich immunoassay, and samples were tested in triplicate (ELISA). The plasma
      levels of VEGF and bFGF varied greatly, i.e., from extremely low to extremely
      high in the two groups, as well as in the healthy individuals. No statistically
      significant difference was found between the two groups or between the patients
      and healthy individuals. Data of the present study therefore showed that VEGF and
      bFGF levels are not valuable biomarkers for predicting treatment outcome.

PMID- 22966373
TI  - Preliminary trial of adjuvant surgery for advanced gastric cancer.
AB  - In patients with stage IV gastric cancer, systemic chemotherapy is the key
      treatment. Combination chemotherapy (cis-diamminedichloride platinum plus S-1 and
      docetaxel plus S-1) results in long-term survival in clinical practice. In
      selected cases, additional (adjuvant) surgery may result in further long-term
      survival. This study aimed to evaluate the efficacy of adjuvant surgery following
      the response to chemotherapy for advanced gastric cancer. Based on response to
      chemotherapy, the indications for adjuvant surgery (surgery after the response to
      chemotherapy) are that resection is expected to be curative rather than
      palliative, provided that no other distant metastases occur. The study included
      20 advanced gastric cancer patients who had undergone gastrectomies after the
      response to the combination chemotherapy of docetaxel and S-1, between September
      2003 and December 2008 at Hiroshima University Hospital. At a median follow-up of
      980 days, the median overall survival was 855 days. A 2- and 3-year survival was
      observed in 80 and 54.9% of patients, respectively, following macroscopic
      curative surgery. In the palliative group, the median overall survival was 510
      days, but a 3-year survival was not observed. In the partial response group, the
      median overall survival was 865 days and a 3-year survival was observed in 37% of
      patients. One-year survival was not observed in the stable disease group. The
      patient survival in the partial response group was statistically more prolonged
      than in the stable disease group. The median overall survival in patients with
      liver metastasis was 865 days, while that in patients with peritoneal
      dissemination was 510 days. In conclusion, adjuvant surgery may be effective in
      gastric cancer patients diagnosed as stage IV by means of liver or distant lymph
      node metastasis, except in cases of peritoneal dissemination.

PMID- 22966374
TI  - Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic
      breast carcinoma: A phase II study.
AB  - Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active
      anthracycline directly to the tumor site, while exposing the patient to a lesser
      degree of doxorubicin-associated toxicities. Recently, a regimen in which
      paclitaxel is infused weekly over 1 h produced substantial antitumor activity
      with little myelosuppression. We designed a phase II trial to study the efficacy
      and toxicity of 10 mg/m(2) PLD on Days 1, 8 and 15, plus 70 mg/m(2) paclitaxel
      weekly in patients with untreated metastatic breast cancer and a high risk of
      cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for
      efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more
      sites of disease. Overall, 4 complete and 16 partial responses were noted with an
      overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive
      disease. Toxicity was found to be manageable in that the only grade 3-4 side
      effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%;
      leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was
      observed. In conclusion, weekly PLD plus paclitaxel appears to be a well
      tolerated and effective approach for metastatic breast cancer patients with a
      high risk of cardiotoxicity.

PMID- 22966375
TI  - Effect of Fraxiparine, a type of low molecular weight heparin, on the invasion
      and metastasis of lung adenocarcinoma A549 cells.
AB  - Lung cancer is one of the most highly malignant tumors, and a significant threat
      to human health. Lung cancer patients often exhibit tumor cell invasion and
      metastasis, which often render current treatments ineffective. Recently, the
      beneficial effects of low molecular weight heparin (LMWH) on cancer metastasis
      were reported in pre-clinical research studies. LMWH may be a potential drug for
      cancer therapy. However, the mechanism of LMWH on the invasion and metastasis of
      cancer has yet to be determined. This study investigated the effects of
      Fraxiparine on the proliferation, invasion and metastasis of the human lung
      adenocarcinoma A549 cell line. MTT assay and flow cytometry showed that
      Fraxiparine slightly inhibited the cell viability dose- and time-dependently, but
      did not arrest the A549 cells in the G1 phase nor induce early apoptosis. The
      transwell chamber assay showed that Fraxiparine significantly suppressed the
      invasion and migration of the A549 cells in vitro. Fraxiparine also markedly
      inhibited the adhesion of the A549 cells to Matrigel. The RT-PCR assay
      demonstrated that the reduction in invasion and metastasis may be related to the
      up-regulation of nm23-H1 and the down-regulation of the heparanase expression.
      Moreover, the RT-PCR assay and Western blot analysis demonstrated that down
      regulation of the expression of integrin beta1 and beta3, as well as that of
      matrix metalloproteinase-2 and -9 may be responsible for the inhibition of the
      invasion and metastasis of A549 cells by Fraxiparine.

PMID- 22966376
TI  - Surgical outcomes and reevaluation of treatment strategies for thymomas.
AB  - Improved histological typing systems for thymic tumors and advances in induction
      and adjuvant therapy have created the need to reevaluate strategies for the
      management of thymoma. We retrospectively studied 73 patients with completely
      resected thymomas unassociated with myasthenia gravis. The World Health
      Organization (WHO) histologic classification, clinicopathological features and
      surgical outcomes were analyzed. Overall survival was 66.2% at 10 years, and the
      median survival time was 169 months. According to the Masaoka staging system,
      overall survival rates at 10 years were 94.7% in stage I, 76.1% in stage II, 30%
      in stage III and 0% in stage IV. In the WHO classification, overall survival
      rates at 10 years were 91.9% in types A and AB, 50.9% in type B2 and not achieved
      in type B3. The disease-free interval was slightly shorter in patients with B2
      and B3 disease than in those with type A, AB and B1 disease. Advanced thymomas
      were significantly associated with type B2 and B3 (p<0.01). In stage III and IV
      disease, adjuvant or neoadjuvant therapy was associated with better survival as
      compared to no adjuvant therapy (p=0.07). On multivariate analysis, Masaoka stage
      III and IV disease and extended thymectomy indicated significant, negative and
      independent risk factors for survival (p<0.01). Masaoka stage I and II thymomas
      or WHO type A and AB thymomas have favorable prognoses and do not require
      postoperative adjuvant therapy. Patients with stage III and IV thymomas require
      additional therapy after surgery.

PMID- 22966377
TI  - Radiosensitizing effect of the histone acetyltransferase inhibitor anacardic acid
      on various mammalian cell lines.
AB  - Agents that enhance the effectiveness of ionizing radiation have been
      investigated over many decades. A relatively new group of potential
      radiosensitizers consists of agents that inhibit histone acetyltransferases
      (HATs). This study evaluated the radiosensitizing properties of the HAT inhibitor
      anacardic acid (AA), used at a low-toxic concentration of 100 MUM in V79, SW1573
      and U2OS cells. Radiation survival curves were analyzed according to the linear
      quadratic model. Significant radiosensitization by AA was only obtained in U2OS
      cells. AA significantly increased the value of the linear parameter alpha, but
      not of the quadratic parameter beta, indicating fixation of potentially lethal
      damage and an intact repair function of sublethal damage. The increase of the
      alpha value was also observed in SW1573 cells, but was not accompanied by a
      significant radiosensitization. A likely explanation for the enhancement of the
      alpha value may be an increase in the amount of lethal lesions due to the
      compacted chromatin structure. Despite the conflicting results of the
      radiosensitizing effect of AA in the three cell lines tested, the ability of AA
      to increase the alpha value suggests potential advantages for clinical
      application.

PMID- 22966378
TI  - [Gd@C(82)(OH)(22)](n) nanoparticles inhibit the migration and adhesion of
      glioblastoma cells.
AB  - In our previous study, [Gd@C(82)(OH)(22)](n), a fullerene-based nanoparticle,
      exhibited potent anti-tumor effects in mouse tumor-bearing models without
      detectable toxicity. The mechanism involved in the anti-tumor effect exerted by
      [Gd@C(82)(OH)(22)](n) remains to be elucidated. This study found that
      glioblastoma cells treated with [Gd@C(82)(OH)(22)](n) nanoparticles showed a
      significant impairment in migration and adhesion by cell chemotaxis, scratch and
      adhesion assays in vitro. Furthermore, our data showed that the key proteins,
      CD40 and ICAM-1, were involved in the inhibition of adhesion in the
      [Gd@C(82)(OH)(22)](n) nanoparticle-treated glioblastoma cells. Thus, our study
      suggests that the [Gd@C(82)(OH)(22)](n) nanoparticle is a new potential anti
      tumor effector and a therapeutic component for malignant glioblastoma
      infiltration.

PMID- 22966379
TI  - Metastin has potential as a suitable biomarker and novel effective therapy for
      cancer metastasis (Review).
AB  - Cancer metastasis is a leading cause of death in cancer patients and is a
      multistep process involving complex interactions between tumor and host cells. To
      metastasize, tumor cells must invade or migrate from the primary tumor and be
      transported to close or distant secondary sites. A tumor cell should successfully
      accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a
      human metastasis suppressor gene that inhibits metastasis of human melanomas and
      breast carcinomas without affecting tumorigenicity. KiSS-1 encodes a carboxy
      terminally amidated peptide with 54 amino-acid residues. The peptide was isolated
      from human placenta as the endogenous ligand of an orphan G-protein-coupled
      receptor and termed 'metastin'. The literature reports metastin related to human
      carcinoma, such as melanoma, thyroid cancer, esophageal squamous cell carcinoma
      (ESCC), hepatocellular carcinoma, pancreatic carcinoma, as well as breast,
      ovarian, bladder and kidney cancer. These malignancies are difficult to treat
      and, even in early-stage cancer, a number of patients develop metastasis shortly
      after surgery. Studies have suggested that metastin inhibits tumor invasion or
      migration through focal adhesion kinase, paxillin, MAP kinase or Rho A.
      Additionally, metastin may be a biomarker in ESCC, pancreatic carcinoma and
      bladder cancer. Metastin has potential as a suitable biomarker in the
      identification of tumors with high metastatic potential and as a novel effective
      treatment modality for patients with metastasis.

PMID- 22966380
TI  - Platelet 12-lipoxygenase and stem cells in Barrett's esophagus.
AB  - Esophageal adenocarcinoma has shown a significant increase in incidence in recent
      years. It is thought that the development of gastroesophageal reflux disease
      (GERD), followed by columnar-lined esophagus and the development of dysplasia,
      leads to invasive adenocarcinoma. The exact pathogenesis of this process, the
      diagnosis and differentiation of the metaplastic and dysplastic esophageal
      lesions have yet to be determined. The purpose of this immunohistochemical study
      was to investigate the expression of pro-tumorigenic enzyme platelet 12
      lipoxygenase (p12LOX) using two new available antibodies in non-dysplastic and
      dysplastic Barrett's esophagus. The stem cell markers nestin, CD117 and CD44,
      were then evaluated. The comparative group included GERD carditis, gastric
      intestinal metaplasia and colorectal adenoma. The overexpression of p12LOX
      detected by two specific antibodies in the non-dysplastic and dysplastic
      Barrett's mucosa clearly demonstrated that this enzyme plays an important role in
      the development of esophageal adenocarcinoma.

PMID- 22966381
TI  - A rare case of Philadelphia chromosome-positive chronic myelogenous leukemia with
      inversion in chromosome 9 and t(10;17).
AB  - The reciprocal translocation t(9;22)(q34;q11), leading to the formation of two
      fusion genes, BCR/ABL and ABL/BCR, is found in 90-95% of cases with chronic
      myeloid leukemia (CML). ABL-BCR expression does not correlate with prognosis, as
      assessed by cytogenetic response, since the ABL/BCR gene is expressed in only a
      proportion of CML patients. This study examined an exceptional BCR/ABL-positive
      CML case with inversion in 9q22q34 leading to the absence of ABL/BCR. Moreover,
      an unbalanced translocation between chromosomes 10 and 17 which caused deletion
      of the TP53 gene was identified. The TP53 gene plays a potential role in CML
      progression, and loss of TP53 may be regarded as a poor prognostic factor.

PMID- 22966382
TI  - A rare chronic myeloid leukemia case with Philadelphia chromosome, BCR-ABL e13a3
      transcript and complex translocation involving four different chromosomes.
AB  - The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic
      myeloid leukemia (CML) patients. Around 5-10% of these patients show complex
      translocations involving other chromosomes in addition to and/or besides
      chromosomes 9 and 22. CML cases with fusion transcripts, such as e13a3, in which
      ABL exon 3 rather than exon 2 has fused to BCR, are extremely rare. Such reported
      cases with the e13a3 transcript showed the Ph chromosome on karyotype analysis.
      This study reported a rare Ph chromosome-positive CML case with new complex
      chromosomal aberrations and an e13a3 BCR-ABL transcript that has yet to be
      established. A four-chromosome translocation involving chromosomal regions
      12p11.2, 19q13.3, 9q34.1 and 22q11.2, besides a trisomy 8 and a derivative
      chromosome 12, were identified using high resolution multicolor banding. Reverse
      transcription polymerase chain reaction products showed the presence of BCR-ABL
      fusion transcript e13a3, and this signifies the major BCR breakpoint. The
      significance of the observed rearrangements and their possible role in the
      progression of CML was investigated.

PMID- 22966383
TI  - A unique complex translocation involving six different chromosomes in a case of
      childhood acute lymphoblastic leukemia with the Philadelphia chromosome and
      adverse prognosis.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy.
      Approximately 84% of cases of ALL are classified as B-precursor ALL, 14% of cases
      are T-cell and 2% of cases are B-cell (B-)ALL. About one third of B-ALL cases
      show an abnormal karyotype. Combining data obtained by immunophenotyping,
      karyotyping and molecular cytogenetic analyses allows for a better understanding
      of this heterogeneous disease. This study reports an exceptional B-ALL case with
      a poor prognosis and unique complex chromosomal aberrations not previously
      observed, i.e., a translocation involving the six chromosomal regions 1q42, 4q21,
      4q24, 4q35 (twice), 8q22 and 10p15.3 besides 9q34 and 22q11.2.

PMID- 22966384
TI  - Pseudoangiomatous stromal hyperplasia: An observation on its microscopic
      involvement in breast carcinoma and the presence of lymph node metastases.
AB  - The spaces of pseudoangiomatous stromal hyperplasia (PASH) are postulated to be
      important in the intramammary spread of breast carcinoma. The present study aimed
      to note the prevalence of inconspicuous, microscopic foci of PASH (identified as
      CD34+ve, CD31-ve and D2-40-ve spaces containing tumour emboli) involved in breast
      carcinoma and to establish the significance of its relationship to lymph node
      metastases. A total of 80 cases of breast carcinoma were examined for microscopic
      foci of PASH permeated by carcinoma and, of the four cases found to demonstrate
      such involvement, three had lymph node metastases.

PMID- 22966385
TI  - Genetic diagnosis of patients with esophageal cancer using FISH.
AB  - This study aimed to the clarify the diagnostic efficacy of fluorescence in situ
      hybridization (FISH) in Kazakh patients with esophageal cancer (EC). FISH was
      compared with the pathological examination of biopsy specimens with DNA probes.
      We enrolled 20 patients, of which 15 were males and 5 females, with an average
      age of 58.3 years, who had abnormal esophaguses on barium radiological digital
      imaging. Touch preparations were performed on biopsy specimens from all of the
      patients and were examined using FISH for chromosomal abnormalities. We compared
      the FISH results with the pathology slides stained with hematoxylin and eosin.
      Classification, according to pathology, identified 2 cases of class II, 3 cases
      of IIIa, 1 case of IIIb, 2 cases of IV, 12 cases of class V and no cases of class
      I. The cases classified as class IIIb or higher were considered to be positive
      for cancer. Using histopathology, 10 cases were diagnosed with squamous cell
      carcinoma and 5 were diagnosed as adenocarcinoma, with one case being false
      negative. Thus, the sensitivity of the pathological examination was 93% and the
      specificity was 100%. Using FISH, 16 cases showed aberrant copy numbers in either
      chromosome 3 or 17. By comparison, pathology did not reveal any false-positive or
      false-negative cases with a sensitivity and specificity of 100%. The centromeres
      of chromosome 3 copy numbers was significantly higher (p=0.035) than the
      centromeres of chromosome 17. Our study compared FISH to diagnose aneusomic
      esophageal cancer cells with the pathology of biopsied tissue. Our findings
      suggest that FISH is a useful and objective assay for the detection of malignant
      cells of esophageal cancer. In our study, the centromeres of chromosome 3 was the
      more sensitive probe for the diagnosis of esophageal cancer in Kazakh patients.

PMID- 22966386
TI  - Array-based profiling of the differential methylation status of CpG islands in
      hepatocellular carcinoma cell lines.
AB  - Alterations in the DNA methylation status particularly in CpG islands are
      involved in the initiation and progression of many types of human cancer. A
      number of DNA methylation alterations have been reported in hepatocellular
      carcinoma (HCC). However, a systematic analysis is required to elucidate the
      relationship between differential DNA methylation status and the characteristics
      and progression of HCC. In the present study, a global analysis of DNA
      methylation using a human CpG-island 12K array was performed on a number of HCC
      cell lines of different origin and metastatic potential. Based on a standard
      methylation alteration ratio of >=2 or <=0.5, 58 CpG island sites and 66 tumor
      related genes upstream, downstream or within were identified. This study showed a
      series of CpG island methylation alterations in the HCC cell lines. The
      expression of various oncogenes, tumor suppressor genes and other key genes were
      up- or downregulated, respectively, resulting in CpG island hypomethylation or
      hypermethylation accordingly. To conclude, a foundation has been provided for
      screening CpG island methylation profiles as HCC biological markers.

PMID- 22966388
TI  - Limitations of tissue microarrays compared with whole tissue sections in survival
      analysis.
AB  - Tissue microarray (TMA) is a promising technique in the evaluation of
      immunohistochemical markers in tumors and may be used as an alternative for whole
      sections. However, only a few studies have correlated a clinical outcome with
      both TMA and results obtained from whole sections. This study compared
      immunostaining for Ki-67 and p16 in TMA (3 cores from each specimen) and whole
      sections of 171 cases of stage III epithelial ovarian cancer with clinical data.
      A high expression of Ki-67 was identified in 85.0, 85.5, 85.8, 90.5 and 84% of
      cores 1, 2 and 3, TMAs and whole tissue sections, respectively. A high p16
      expression was found in 36.5, 31.4, 30.3, 46.3 and 31.0% of cores 1, 2 and 3,
      TMAs and whole tissue sections, respectively. The high expression of Ki-67 and
      p16 in whole tissue sections significantly correlated with that of Ki-67 and p16
      in core 1 (P<0.0001 and P<0.0001, respectively), core 2 (P<0.0001 and P<0.0001,
      respectively), core 3 (P<0.0001 and P<0.0001, respectively), and TMAs (P<0.0001
      and P<0.0001, respectively). In univariate analysis, a high expression of Ki-67
      and p16 in two of the cores; TMA and the whole tissue sections were significantly
      correlated to disease-related survival (Ki-67: P=0.008, 0.012, 0.012 and 0.0001,
      respectively, and p16: P=0.0007, 0.0005, 0.0008 and 0.005, respectively).
      However, in the multivariate analysis only Ki-67 on whole tissue sections
      retained an independent prognostic significance (P=0.025). We concluded that more
      studies, with a higher number of cores, are necessary to determine the efficacy
      of TMA in reflecting the prognostic value of different antibodies. Morever,
      evaluation of this method is crucial for each type of tumor and each separate
      antigen. It is also essential to confirm the clinical correlations on the whole
      sections before investigating the same parameters on TMA.

PMID- 22966387
TI  - A pilot study on morphology and the mechanism involved in linearly patterned
      programmed cell necrosis in melanoma.
AB  - Accumulating data provide evidence that autophagy contributes to programmed cell
      death (PCD) under certain circumstances. Immunohistochemistry and real-time PCR
      were performed to investigate the correlation the expression of autophagy-related
      proteins LC3 and Atg4B and linearly patterned programmed cell necrosis (LPPCN) in
      melanoma. LPPCN was recently reported to be a special PCD, which is similar to
      neither apoptosis nor conventional necrosis commonly observed in tumoral tissues.
      The mechanism involved in LPPCN remains unclear. Our data showed that the
      expression of LC3 and Atg4B in the LPPCN-positive group was significantly higher
      than that in the LPPCN-negative group regarding protein and mRNA levels (p<0.05).
      Based on morphological observation, immunohistochemistry and real-time PCR
      experiments in this study, it was concluded that autophagy may play a crucial
      role in the process of LPP+CN in melanoma. This study provides novel insights
      into the mechanism that regulates LPPCN in vivo during tumor development. We
      speculated that LPPCN may be an early stage event in tumoral neovascularization
      under hypoxic-microenvironmental conditions. Accordingly, LPPCN can be considered
      a novel target in the process of antiangiogenesis treatment, which can be
      expected to obtain a better clinical outcome in the future.

PMID- 22966389
TI  - Usefulness of (18)F-FDG positron emission tomography/computed tomography for the
      diagnosis of pyothorax-associated lymphoma: A report of three cases.
AB  - Pyothorax-associated lymphoma (PAL) is a unique and rare non-Hodgkin's lymphoma
      developing in the pleural cavity following a long-standing history of chronic
      pyothorax (CP). The development of F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron
      emission tomography combined with computed tomography (PET/CT) has contributed to
      the evaluation of lymphoma staging. However, only a few studies describing FDG
      PET/CT findings in PAL have been published. This study reported three cases of
      PAL; all 3 patients had previously undergone artificial collapse therapy for
      pulmonary tuberculosis. Both the first case (an 84-year-old male) and second case
      (an 83-year-old male) complained of abdominal pain. An ultrasound scan revealed a
      mass shadow in the left chest wall without abnormal findings in the abdomen, and
      the CT and magnetic resonance imaging scans suggested malignant lymphoma of the
      left chest. FDG-PET/CT imaging showed extremely intense FDG uptake only in the
      left pleura and chest wall. Diagnosis was CP in the two patients, showing a high
      maximum standardized uptake value (SUVmax: early, 14.8 and delayed, 19.4 in the
      first case; early, 20.8 and delayed, 27.3 in the second case, respectively).
      Histopathological analysis of the specimens obtained by biopsy of the PET/CT
      positive pleural mass showed non-Hodgkin's, diffuse large B cell lymphoma in the
      two cases. The third case was a 79-year-old male with relapse after right
      pleuropneumonectomy for PAL (diffuse large B cell lymphoma) 4 years earlier.
      PET/CT showed intense FDG uptake (SUVmax: early, 19.9 and delayed, 35.7) in the
      right pleura and chest wall. Diagnosis was CP, suggesting the recurrence of PAL.
      Furthermore, abnormal intense FDG uptake was noted in the hilar, mediastinal and
      supraclavicular lymph nodes, as well as in the spleen. In conclusion, FDG-PET/CT
      imaging is useful in the evaluation of the area of invasion in PAL.

PMID- 22966390
TI  - Association of ATP7A expression and in vitro sensitivity to cisplatin in non
      small cell lung cancer.
AB  - Expression of copper-transporting P-type adenosine triphosphatase A (ATP7A) is
      reportedly associated with platinum drug resistance in various types of solid
      tumors. However, the impact of ATP7A expression on platinum drug resistance in
      non-small cell lung cancer (NSCLC) has yet to be adequately elucidated. In vitro
      cisplatin (CDDP) sensitivity was investigated using the collagen gel-droplet
      embedded culture drug sensitivity test, and the ATP7A mRNA expression levels were
      assessed by real-time polymerase chain reaction in surgically resected specimens
      of NSCLC. The relationship between the ATP7A expression levels and the in vitro
      CDDP sensitivity was then evaluated. The ATP7A mRNA expression levels in the CDDP
      resistant tumors were significantly higher than those in the CDDP-sensitive
      tumors (p=0.0167, Mann-Whitney U test). In conclusion, the results suggest that
      evaluation of ATP7A expression is useful as a marker for cisplatin
      chemoresistance.

PMID- 22966391
TI  - Giant serous microcystic adenoma of the pancreas safely resected after
      preoperative arterial embolization.
AB  - Serous microcystic adenomas are rare and account for 1-2% of all exocrine
      pancreatic tumors and 25% of all pancreatic cystic neoplasms. Recently, with
      advances in imaging techniques, these adenomas have been identified at an
      increasing frequency. A 63-year-old woman visited her doctor in 1999 due to a
      gastric deformity detected by upper gastrointestinal endoscopy. An abdominal
      computed tomography scan revealed a cystic lesion measuring 6.0 cm in diameter,
      resulting in a diagnosis of serous microcystic adenoma of the pancreatic head.
      During follow-up, the tumor increased steadily in size, measuring 6.0 cm in
      diameter in 1999 and 13.0 cm in 2008, while remaining asymptomatic throughout
      this period of time. The risk of malignant transformation appears to be low even
      over the long-term. However, some cases of malignant transformation to serous
      cystadenocarcinoma have recently been reported. In this case, assessment of the
      relationship between the tumor and adjacent vascular structures, such as massive
      drainage vein development on the surface or tumor flow into the portal and
      superior mesenteric veins and the celiac and superior mesenteric arteries, was
      critical for determining tumor resectability. The risk of massive intra-operative
      hemorrhage was felt to be considerable, given the extent of the veins on the
      surface of the tumor, as well as the size and location of the primary pancreatic
      mass. Therefore, preoperative embolization of the tumor-feeding arteries arising
      from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was
      performed. Tumor resection with pancreaticoduodenectomy was performed without a
      blood transfusion, with an estimated blood loss of 570 ml. The final pathology
      confirmed the diagnosis of serous microcystic adenoma. The patient is currently
      alive and disease-free. Preoperative partial embolization of the tumor feeding
      arteries and intra-operative resection of the right gastric and inferior
      pancreatoduodenal arteries, allowed the tumor blood supply to be arrested without
      preoperative tumor necrosis. Subsequently, intraoperative blood loss was reduced.
      Preoperative partial embolization of the feeding arteries is useful for the
      resection of hypervascular large tumors of the pancreas.

PMID- 22966392
TI  - CXCR7 protein expression correlates with elevated mmp-3 secretion in breast
      cancer cells.
AB  - Metastatic breast cancer is the leading cause of cancer-related death in women
      worldwide and, despite recent therapeutic advances, the disease remains
      incurable. A critical step in cancer cell metastasis is the degradation of
      extracellular matrix components by matrix metalloproteinases (MMPs), which
      permits malignant cells to separate from the primary tumor and access circulatory
      conduits for seeding distant organs. This study reports a correlation between the
      elevated secretion of MMP-3 by breast cancer cells and the expression of CCR7
      protein, a recently discovered non-classical chemokine receptor that may play a
      role in metastasis by regulating tumor cell transendothelial migration. MMP-3
      secretion is increased in human mammary tumor cells that overexpress CXCR7, and
      is reduced in mouse breast cancer cells in which the endogenous CXCR7 expression
      has been knocked down via RNAi. The correlation between CXCR7 and MMP-3
      expression in breast cancer may provide additional therapeutic rationale for
      targeting CXCR7 in order to prevent metastatic disease.

PMID- 22966393
TI  - Infectious background of febrile advanced lung cancer patients who received
      chemotherapy.
AB  - The study aimed to determine the diagnostic utility of procalcitonin (PCT) in
      order to discriminate between infective fever and fever due to inflammation in
      febrile advanced lung cancer patients treated with cytotoxic chemotherapy. A
      total of 121 patients with advanced lung cancer, treated with a cytotoxic
      chemotherapy regimen between September 2007 and September 2008 at Kyoto
      University Hospital, were recruited. Blood samples were obtained on the first day
      of the fever. Serum c-reactive protein (CRP) and PCT levels were measured. At
      least two blood cultures were performed, and sputum was taken for Gram staining
      and culture. There were 71 episodes in 61 patients in the 12 months of the study,
      representing 50.4% of our study population. A total of 41 patients (57.7%) were
      diagnosed with pneumonia using imaging modalities, 6 (8.5%) with bacteremia using
      blood culture and 4 (5.6%) with urinary tract infections using urine culture.
      Among the 41 pneumonia cases, culture from sputum revealed pathologic bacteria in
      21 (51.2%) and fungal disease in 14 (34.1%) cases. Among the 71 febrile episodes,
      serum procalcitonin and CRP were measured in 50 episodes. Serum procalcitonin
      positive patients showed poor outcomes on antibiotics therapy (Fisher's exact
      test, p=0.042). Furthermore, serum procalcitonin positivity was able to
      discriminate infective fever from fever due to inflammation (Chi-square test,
      p=0.001). We showed the causative organisms of febrile advanced lung cancer
      patients who received cytotoxic chemotherapy, as well as the possibility of PCT
      to discriminate infective fever from fever due to inflammation.

PMID- 22966394
TI  - Addition of transcatheter arterial chemoembolization decreased local recurrence
      but had no survival benefit to percutaneous ethanol injection therapy for
      patients with small hepatocellular carcinoma: A multicenter randomized control
      study.
AB  - To assess the efficacy of the additional treatment of transcatheter arterial
      chemoembolization (TACE) to percutaneous ethanol injection (PEI) therapy for
      relatively small hepatocellular carcinomas (HCCs), a multicenter randomized
      control study (RCT) was performed. We conducted an RCT and follow-up study during
      the enrollment period from 1997 to 1999. Newly diagnosed patients with one to
      three HCC tumors measuring from 2 to 4 cm (4 cm maximum) in diameter were
      enrolled. A total of 30 patients initially underwent a combination TACE-PEI or
      PEI-alone therapies at eight randomly assigned Japanese hospitals. However, 3
      patients withdrew. Of the 27 remaining patients, 13 were treated with the
      combination TACE-PEI therapy and 14 with PEI therapy alone. The patients were
      observed over several months [median (interquartile range) 33.2 (24.6) months].
      There were no significant differences in the background of the patients between
      the two groups. Among the patients treated with TACE-PEI, the development of a
      local residual tumor was of significantly lower occurence, compared to the group
      receiving PEI alone (7.6 and 42.9%, respectively; P=0.024). However, the mean
      cancer-free time (absence of local or multiple nodule recurrence) or patient
      survival time was not significantly different between the two groups [PEI alone
      vs. TACE-PEI: cancer-free time 16.7 (95% CI 7.3-26.0) vs. 22.9 months (95% CI
      12.4-33.4); survival time 57.2 (95% CI 37.2-77.2) vs. 42.4 months (95% CI 29.2
      55.6)]. Although the combination of TACE and PEI had significant effects on the
      local tumor control, no efficacy of the addition of TACE to PEI was noted in the
      prognosis among patients with relatively small HCC tumors.

PMID- 22966395
TI  - Incidental events of diaphragmatic surgery in 82 patients with advanced ovarian,
      primary peritoneal and fallopian tubal cancer.
AB  - Surgical resections, such as peritoneal stripping (peritonectomy) are performed
      for disseminated diaphragmatic lesions of advanced ovarian cancer. This study
      retrospectively investigated the incidental events of diaphragmatic surgery. The
      records of patients with advanced mullerian carcinomas, including ovarian,
      primary peritoneal and fallopian carcinomas, who underwent diaphragmatic surgery
      were reviewed. Based on our criteria, stripping was performed for surface disease
      on the diaphragm, and full-thickness resection was performed for bulky disease.
      In certain cases, both procedures were performed. We analyzed intra- and post
      operative incidental events in 82 patients. The chi(2) and Fisher's exact tests
      were used in the statistical analysis. There were 82 stage III-IV cases of which
      56 patients underwent stripping, 12 underwent full-thickness resection and 14
      patients underwent both procedures. Unexpected open chest surgery following
      stripping occurred in 1 out of 63 patients (1.6%) in the primary, 4 out of 13
      patients (30.8%) in the interval and 0 out of 6 patients (0.0%) in the secondary
      debulking surgery groups. The incidence of unexpected open chest surgery was high
      in the interval debulking surgery group (p<0.001). Regarding post-operative
      events, accumulation of pleural effusion was identified in 43 patients (52.4%).
      The incidence of pleural effusions was not significantly different between the
      two procedures. No complications were encountered, nor was a chest tube required,
      during unexpected open chest surgery and postoperative pleural effusions.
      Therefore, it was concluded that special attention should be paid during interval
      debulking surgery even though it was possible for surgical resections of
      diaphragmatic lesions to be performed safely.

PMID- 22966396
TI  - Methylated BNIP3 gene in colorectal cancer prognosis.
AB  - The DNA methylation of apoptosis-related genes in various cancers contributes to
      the disruption of the apoptotic pathway and results in resistance to
      chemotherapeutic agents. Irinotecan (CPT-11) is one of the key chemotherapy drugs
      used to treat metastatic colorectal cancer (CRC). However, a number of metastatic
      CRC patients do not benefit from this drug. Thus, the identification of molecular
      genetic parameters associated with the response to CPT-11 is of interest. To
      identify apoptosis-related genes that may contribute to CPT-11 resistance,
      microarray analysis was conducted using colon cancer cells in which 5-aza
      2'deoxycytidine (DAC) enhanced sensitivity to CPT-11. Microarray analysis
      identified 10 apoptosis-related genes that were up-regulated following treatment
      with DAC. Among the genes, Bcl-2/adenovirus E1B 19 kDa protein interacting
      protein 3 (BNIP3), a Bcl-2 family pro-apoptotic protein, was identified as being
      involved in CPT-11 resistance following methylation of its promoter. An analysis
      of 112 primary CRC cases revealed that approximately 58% of cases showed BNIP3
      methylation, and that patients with methylation exhibited a poorer outcome
      compared to those without methylation. In addition, in 30 patients who received
      first-line CPT-11 chemotherapy, patients with methylation exhibited resistance to
      chemotherapy compared to patients with no methylation. The results suggest that
      methylation of BNIP3 is a predictive factor in the prognosis and response to CPT
      11 treatment in CRC patients.

PMID- 22966397
TI  - Nodal metastasis in well-differentiated follicular carcinoma of the thyroid: Its
      incidence and clinical significance.
AB  - The clinical significance of nodal metastasis in well-differentiated follicular
      carcinoma (WD-FC) of the thyroid remains a controversial issue. This study aimed
      to clarify clinical and pathological characteristics of WD-FC with nodal
      metastasis, based on the new WHO classification. We examined 249 WD-FC cases
      diagnosed between 1983 and 2004 in our hospital. Poorly differentiated follicular
      carcinoma was not included in this study. Of the 249 WD-FC cases, 9 (3.6%)
      revealed nodal metastasis. The incidences of nodal metastasis in minimally
      invasive and widely invasive cases were 2.0 and 9.8%, respectively. In four
      patients, nodal metastasis was detected in the ipsilateral lymph nodes during the
      initial surgery. A total of 6 patients presented with nodal metastasis 2-10 years
      after the initial operation, and 3 patients with bilateral and large nodal
      metastases were relatively young. No patients succumbed to the carcinoma. Primary
      lesions of WD-FC with nodal metastasis were microscopically conventional, and
      there were no findings predicting nodal metastasis. We hypothesized that the
      incidence of nodal metastasis in WD-FC, based on the new WHO classification, was
      lower compared with previous reports. Younger individuals may be at a higher risk
      of large bilateral nodal metastasis. The presence of nodal metastasis did not
      affect the long-term outcome of follicular carcinoma.

PMID- 22966398
TI  - Effects of photodynamic therapy for superficial esophageal squamous cell
      carcinoma in vivo and in vitro.
AB  - Photodynamic therapy (PDT) is an ablative treatment leading to intracellular
      photoexcitation and injury. A total of 15 patients with superficial esophageal
      squamous cell carcinoma (ESCC) without metastasis underwent PDT and 48-72 h after
      intravenous Photofrin, the patients were treated with a 630-nm excimer dye laser.
      A total of 13 patients had local tumor recurrence after definitive
      chemoradiotherapy (CRT) consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP).
      Of 6 patients, 5 had submucosal ESCC and were treated with S-1. Complete reponse
      was achieved by 11 patients with initial PDT, but 2 had recurrences. The
      recurrent/residual tumors were successfully treated with repeated PDT. Two
      patients with intramucosal ESCC succumbed due to metastatic disease, but 11
      patients were disease-free. The 5 patients treated with S-1 remained alive
      despite submucosal ESCC. PDT was applied to human ESCC cells in vitro in the
      presence or absence of 5-FU or CDDP. The combination of PDT with 5-FU or CDDP
      resulted in enhanced cytotoxic effects, thereby reducing the effective dosage of
      each drug. PDT is a promising treatment option for selected ESCC cases,
      particularly for local recurrence following CRT. Our experience suggests that PDT
      is more effective when combined with chemotherapy.

PMID- 22966399
TI  - Absence of R140Q mutation of isocitrate dehydrogenase 2 in gliomas and breast
      cancers.
AB  - Somatic mutations of isocitrate dehydrogenase (IDH)-1 and IDH2 proteins have been
      described in gliomas. The mutations target the R132 amino acid residue and the
      R172 residue in IDH1 and IDH2, respectively. The same mutations were observed in
      acute myeloid leukemias with normal karyotype, but a new mutation in IDH2 (R140Q
      substitution) was detected in malignant myeloid diseases and appears to be the
      most frequent IDH mutation in these pathologies. To the best of our knowledge, no
      study thus far has reported the presence of this R140Q mutation in IDH2 in tumors
      of the nervous system and breast cancers. We evaluated IDH1 and IDH2 exon 4 in 48
      low-grade gliomas, 58 primary glioblastomas and 94 breast cancers to evaluate the
      frequency of mutation and investigated the R140Q substitution in IDH2. The
      results were compared to our recently obtained results in hematopoietic diseases.
      The frequency of IDH1 and IDH2 mutations in our panel of gliomas was similar to
      previously reported mutations. No IDH2 R140 mutation was observed. Compared to
      hematopoietic diseases, the IDH2 R172 mutation was also more rare and IDH1
      mutations more prominent in tumors of the nervous system. No IDH1 or IDH2
      mutation was detected in the 94 breast cancer samples. Thus, the IDH2 R140
      mutation appears to be restricted to hematopoietic diseases.

PMID- 22966400
TI  - Synovial sarcoma individual chemotherapy directed by collagen gel droplet
      embedded culture drug sensitivity test: A case report.
AB  - The collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is an
      anticancer drug sensitivity test developed about 10 years ago. This study reports
      the application of this test in the choice of neoadjuvant chemotherapy for the
      treatment of one patient with a large synovial sarcoma in the right shank. A 28
      year old man presented at our hospital with a large mass in his right shank which
      had a hard texture and an obscure boundary. The histopathological diagnosis of
      excisional biopsy specimens was synovial sarcoma with low differentiation.
      Theprubicin/Cisplatin (THP/CDDP) neoadjuvant chemotherapy was selected based on
      the results obtained from the CD-DST. After three courses, a computed tomography
      (CT) scan was performed which indicated that the volume of the tumor had
      decreased significantly. Additionally, tumor necrosis, as well as the clinical
      response, showed complete response. The histopathological diagnosis of wide
      excision specimens indicated a grade III chemotherapy response. The patient was
      alive and without recurrence after a follow-up of 16 months. Our results
      indicated that the CD-DST is a useful tool for selecting neoadjuvant
      chemotherapeutic drugs for patients with synovial sarcoma.

PMID- 22966401
TI  - Medullary thyroid carcinoma relapse reversed with dichloroacetate: A case report.
AB  - A 51-year-old male patient diagnosed with medullary thyroid carcinoma (MTC) in
      2001, with progression to lung metastases following adriamycin therapy, was then
      successfully treated with dimethyltriazenoimidazole carboximide. He remained in
      partial remission for 7 years following numerous chemotherapy attempts to induce
      partial remission. In October 2008, the patient, then 58 years old, relapsed with
      numerous tumors throughout his central body. On December 1, 2008, the tumor
      marker for MTC, calcitonin, was at 38,611 pg/ml, i.e., much higher than the norm
      of <20 pg/ml. Since all other chemotherapy attempts had failed, he was ineligible
      for any new studies. Subsequently, the patient was immediately started on 10
      mg/kg of dichloroacetate (DCA). By April 2009, the calcitonin level was reduced
      to 2,000 pg/ml. In May 2009, a new positron emission tomography showed a dramatic
      reduction in all tumor locations. The patient presently remains in remission and
      continues receiving the same dosage of DCA, with his tumor marker remaining
      stable in laboratory data since November 2009.

PMID- 22966402
TI  - Hypoxia-inducible factor-1alpha enhances the malignant phenotype of multicellular
      spheroid HeLa cells in vitro.
AB  - The purpose of this study was to clarify the direct effect of hypoxia-inducible
      factor-1alpha (HIF-1alpha) on tumor growth, apoptosis and migration in vitro. To
      achieve this aim, a comparison was made of the differences in growth rates,
      apoptotic indices and cell invasive ability in the human cervical cancer cell
      line HeLa and the HIF-1alpha-blocked counterpart in a three-dimensional spheroid
      culture. A significant decrease in cell proliferation and invasion, and an
      increase in cell apoptosis were observed in HIF-1alpha-blocked cells in the three
      dimensional culture. The data indicated that a multicellular spheroid culture is
      an ideal model of hypoxia in vitro and that HIF-1alpha is a significant regulator
      of adaptive processes that promote tumor cell malignant phenotypes, such as
      proliferation, anti-apoptosis and invasive ability.

PMID- 22966403
TI  - Value of napsin A and thyroid transcription factor-1 in the identification of
      primary lung adenocarcinoma.
AB  - Napsin A is a newly discovered functional aspartic proteinase that is expressed
      in normal lung parenchyma in type II pneumocytes and is thought to be associated
      with primary lung adenocarcinoma. Thyroid transcription factor-1 (TTF-1) is a
      widely used relatively restricted marker for lung adenocarcinoma. The present
      study aimed to compare the usefulness of napsin A with TTF-1 for the
      identification of primary lung adenocarcinoma. Immunohistochemical expression of
      napsin A and TTF-1 was analyzed in 351 lung cancer tissues, including 27
      metastases. Napsin A was expressed in 180 of 212 (84.9%) primary lung
      adenocarcinomas, while no expression was noted in all 27 metastatic lung cancer
      specimens, including 19 metastatic adenocarcinomas. In contrast, TTF-1 expression
      was not only noted in 179 of 212 (84.4%) primary lung adenocarcinomas, but also
      in 12 of 18 (66.7%) small-cell carcinomas and some of the squamous carcinomas, as
      well as in one metastatic adenocarcinoma from the thyroid. The sensitivity and
      specificity of napsin A for primary lung adenocarcinoma (84.9 and 93.8%,
      respectively) were higher than the sensitivity and specificity of TTF-1 (84.4 and
      83.9%, respectively). By combining napsin A and TTF-1, sensitivity increased to
      91.0%. Furthermore, the sensitivity and specificity expression was associated
      with gender, smoking history, performance status, pathological type, primary
      tumor size and nodal metastasis. Therefore, napsin A is a useful novel marker in
      the differential diagnosis of primary lung adenocarcinoma.

PMID- 22966404
TI  - Comparison of survival rates between patients treated with transcatheter arterial
      chemoembolization and hepatic resection for solitary hepatocellular carcinoma.
AB  - The present study aimed to retrospectively compare the survival rates between
      patients treated with transcatheter arterial chemoembolization and hepatic
      resection for solitary hepatocellular carcinoma (HCC). According to our database,
      derived from three affiliated hospitals, the inclusion criteria for this study
      were: solitary HCC [Child-Pugh class A and International Union Against Cancer
      (UICC) stage T1-3N0M0] treated between July 1990 and October 2001. Subsequently,
      hepatic resection (149 patients) as well as chemoembolization (102 patients)
      groups were selected. Following stratification according to tumor stage [UICC,
      Cancer of the Liver Italian Program (CLIP) and Milan criteria], survival rates
      were compared between the treatment groups. Survival rates were calculated using
      the Kaplan-Meier method. Age, gender and size of the HCC did not differ
      significantly between the groups. Moreover, no significant difference in the
      survival rates (average hepatic resection, 58.9 months; average
      chemoembolization, 45 months; P=0.1697) was observed between the groups. In the
      subgroup analysis, according to tumor stage, the survival rate was significantly
      higher for the hepatic resection group than for the chemoembolization group in
      the UICC T3N0M0 (P=0.017) subgroup. However, no significant differences in
      survival rates were observed between the hepatic resection and chemoembolization
      groups for UICC T1 (P=0.7329), T2N0M0 (P=0.5741), CLIP0 (P=0.3593), CLIP1-2
      (P=0.3287) and within (>5 cm; P=0.4429) and beyond Milan criteria (<=5 cm;
      P=0.4003) subgroups. Chemoembolization is as effective as hepatic resection in
      treating solitary HCC in subpopulations with UICC T1-2N0M0 or CLIP 0-2 HCC or
      Milan criteria and adequate liver function. In the subgroup with UICC T3N0M0 HCC,
      hepatic resection is superior to chemoembolization.

PMID- 22966405
TI  - Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella
      sativa L., in a rat multi-organ carcinogenesis bioassay.
AB  - Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has
      been widely used for various medicinal and nutritional purposes. Volatile oil
      extracts along with its major constituents, such as thymoquinone, have recently
      attracted considerable attention for their antioxidant, immunoprotective and
      antitumor properties. The present study was conducted to assess the
      chemopreventive potential of crude oils in N. sativa on tumor formation using a
      well-established rat multi-organ carcinogenesis model featuring initial treatment
      with five different carcinogens. Post-initiation administration of 1000 or 4000
      ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks
      significantly reduced malignant and benign colon tumor sizes, incidences and
      multiplicities. The treatment also significantly decreased the incidences and
      multiplicities of tumors in the lungs and in different parts of the alimentary
      canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling
      indices, reflecting cell proliferation were significantly decreased in various
      organs and lesions after treatment with the two doses of N. sativa. The plasma
      levels of insulin growth factor, triglycerides and prostaglandin E2 were also
      altered. The findings show, for the first time, that N. sativa administration
      exerts potent inhibitory effects on rat tumor development and on cellular
      proliferation in multiple organ sites. In particular, the ability to
      significantly inhibit murine colon, lung, esophageal and forestomach tumors was
      demonstrated in the post-initiation phase, with no evidence of clinical side
      effects. The mechanisms are likely to be related to suppression of cell
      proliferation.

PMID- 22966406
TI  - Coexistence of copy number increases of ZNF217 and CYP24A1 in colorectal cancers
      in a Chinese population.
AB  - Evidence suggests that the amplification of chromosome 20q13 is common in
      colorectal cancers (CRCs). Certain candidate oncogenes located in this region are
      reported to be associated with tumorigenesis of the gastrointestinal tract. The
      functional impact of such regions should be extensively investigated in a large
      number of clinical samples. In this study, 145 CRC samples with matched adjacent
      normal tissues were collected from a Chinese population for copy number variation
      (CNV) analysis. Our results showed that both the copy numbers of 25-hydroxy
      vitamin D3 24-hydroxylase (CYP24A1) and zinc-finger protein 217 (ZNF217) were
      amplified in a relatively high percentage of CRC samples (51.1 and 60%,
      respectively). The mRNA expression levels of both CYP24A1 and ZNF217 were found
      to have increased in the collected CRC samples as compared to the matched
      adjacent normal tissues. ZNF217, but not CYP24A1, showed a positive correlation
      between copy number increases and mRNA overexpression. These findings suggest the
      potential role of CNVs of certain oncogenes in CRCs.

PMID- 22966407
TI  - Science to improve care for people affected by unhealthy alcohol and other drug
      use.

PMID- 22966408
TI  - Comment on the case for considering quality of life in addiction research and
      clinical practice.

PMID- 22966409
TI  - Return to drug use and overdose after release from prison: a qualitative study of
      risk and protective factors.
AB  - BACKGROUND: Former inmates are at high risk for death from drug overdose,
      especially in the immediate post-release period. The purpose of the study is to
      understand the drug use experiences, perceptions of overdose risk, and
      experiences with overdose among former prisoners. METHODS: This qualitative study
      included former prison inmates (N=29) who were recruited within two months after
      their release. Interviewers conducted in-person, semi-structured interviews which
      explored participants' experiences and perceptions. Transcripts were analyzed
      utilizing a team-based method of inductive analysis. RESULTS: The following
      themes emerged: 1) Relapse to drugs and alcohol occurred in a context of poor
      social support, medical co-morbidity and inadequate economic resources; 2) former
      inmates experienced ubiquitous exposure to drugs in their living environments; 3)
      intentional overdose was considered "a way out" given situational stressors, and
      accidental overdose was perceived as related to decreased tolerance; and 4)
      protective factors included structured drug treatment programs,
      spirituality/religion, community-based resources (including self-help groups),
      and family. CONCLUSIONS: Former inmates return to environments that strongly
      trigger relapse to drug use and put them at risk for overdose. Interventions to
      prevent overdose after release from prison may benefit from including structured
      treatment with gradual transition to the community, enhanced protective factors,
      and reductions of environmental triggers to use drugs.

PMID- 22966410
TI  - Patient preferences for emergency department-initiated tobacco interventions: a
      multicenter cross-sectional study of current smokers.
AB  - BACKGROUND: The emergency department (ED) visit provides a great opportunity to
      initiate interventions for smoking cessation. However, little is known about ED
      patient preferences for receiving smoking cessation interventions or correlates
      of interest in tobacco counseling. METHODS: ED patients at 10 US medical centers
      were surveyed about preferences for hypothetical smoking cessation interventions
      and specific counseling styles. Multivariable linear regression determined
      correlates of receptivity to bedside counseling. RESULTS: Three hundred seventy
      five patients were enrolled; 46% smoked at least one pack of cigarettes per day,
      and 11% had a smoking-related diagnosis. Most participants (75%) reported
      interest in at least one intervention. Medications were the most popular (e.g.,
      nicotine replacement therapy, 54%), followed by linkages to hotlines or other
      outpatient counseling (33-42%), then counseling during the ED visit (33%).
      Counseling styles rated most favorably involved individualized feedback (54%),
      avoidance skill-building (53%), and emphasis on autonomy (53%). In univariable
      analysis, age (r=0.09), gender (average Likert score=2.75 for men, 2.42 for
      women), education (average Likert score=2.92 for non-high school graduates, 2.44
      for high school graduates), and presence of smoking-related symptoms (r=0.10)
      were significant at the p<0.10 level and thus were retained for the final model.
      In multivariable linear regression, male gender, lower education, and smoking
      related symptoms were independent correlates of increased receptivity to ED-based
      smoking counseling. CONCLUSIONS: In this multicenter study, smokers reported
      receptivity to ED-initiated interventions. However, there was variability in
      individual preferences for intervention type and counseling styles. To be
      effective in reducing smoking among its patients, the ED should offer a range of
      tobacco intervention options.

PMID- 22966411
TI  - Risk of future trauma based on alcohol screening scores: a two-year prospective
      cohort study among US veterans.
AB  - BACKGROUND: Severe alcohol misuse as measured by the Alcohol Use Disorders
      Identification Test-Consumption (AUDIT-C) is associated with increased risk of
      future fractures and trauma-related hospitalizations. This study examined the
      association between AUDIT-C scores and two-year risk of any type of trauma among
      US Veterans Health Administration (VHA) patients and assessed whether risk varied
      by age or gender. METHODS: Outpatients (215, 924 male and 9168 female) who
      returned mailed AUDIT-C questionnaires were followed for 24 months in the medical
      record for any International Statistical Classification of Diseases and Related
      Health Problems (ICD-9) code related to trauma. The two-year prevalence of trauma
      was examined as a function of AUDIT-C scores, with low-level drinking (AUDIT-C 1
      4) as the reference group. Men and women were examined separately, and age
      stratified analyses were performed. RESULTS: Having an AUDIT-C score of 9-12
      (indicating severe alcohol misuse) was associated with increased risk for trauma.
      Mean (SD) ages for men and women were 68.2 (11.5) and 57.2 (15.8), respectively.
      Age-stratified analyses showed that, for men<=50 years, those with AUDIT-C
      scores>=9 had an increased risk for trauma compared with those with AUDIT-C
      scores in the 1-4 range (adjusted prevalence, 25.7% versus 20.8%, respectively;
      OR=1.24; 95% confidence interval [CI], 1.03-1.50). For men>=65 years with average
      comorbidity and education, those with AUDIT-C scores of 5-8 (adjusted prevalence,
      7.9% versus 7.4%; OR=1.16; 95% CI, 1.02-1.31) and 9-12 (adjusted prevalence 11.1%
      versus 7.4%; OR=1.68; 95% CI, 1.30-2.17) were at significantly increased risk for
      trauma compared with men>=65 years in the reference group. Higher AUDIT-C scores
      were not associated with increased risk of trauma among women. CONCLUSIONS: Men
      with severe alcohol misuse (AUDIT-C 9-12) demonstrate an increased risk of
      trauma. Men>=65 showed an increased risk for trauma at all levels of alcohol
      misuse (AUDIT-C 5-8 and 9-12). These findings may be used as part of an evidence
      based brief intervention for alcohol use disorders. More research is needed to
      understand the relationship between AUDIT-C scores and risk of trauma in women.

PMID- 22966412
TI  - Effect of antioxidant mineral elements supplementation in the treatment of
      hypertension in albino rats.
AB  - Oxidative stress has been implicated in various pathologies, including
      hypertension, atherosclerosis, diabetes, and chronic renal disease. The current
      work was designed with the aim of investigating the potentials of antioxidants
      copper, manganese, and zinc in the treatment of hypertension in Wistar rats. The
      rats were fed 8% NaCl diet for 5 weeks and treatment with supplements in the
      presence of the challenging agent for additional 4 weeks. The supplementation
      significantly decreased the blood pressure as compared with hypertensive control.
      The result also indicated significant decreased in the levels of total
      cholesterol, triglyceride, low-density lipoprotein cholesterol and very low
      density lipoprotein cholesterol, malondialdehyde, insulin and increase in the
      high-density lipoprotein cholesterol, total antioxidant activities, and nitric
      oxide of the supplemented groups relative to the hypertensive control. The
      average percentage protection against atherogenesis indicated 47.13 +/- 9.60% for
      all the supplemented groups. The mean arterial blood pressure showed significant
      positive correlation with glucose, total cholesterol, triglyceride, low-density
      lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic
      index, insulin resistance and malondialdehyde while high density lipoprotein
      cholesterol and total antioxidant activities showed negative correlation. The
      result therefore indicated strong relationship between oxidative stress and
      hypertension and underscores the role of antioxidant minerals in reducing
      oxidative stress, dyslipidemia, and insulin resistance associated with
      hypertension.

PMID- 22966413
TI  - Intensification of doxorubicin-related oxidative stress in the heart by
      hypothyroidism is not related to the expression of cytochrome P450 NADPH
      reductase and inducible nitric oxide synthase, as well as activity of xanthine
      oxidase.
AB  - Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine
      oxidase play an important role in the antracycline-related cardiotoxicity. The
      expression of P450R and iNOS is regulated by triiodothyronine. The aim of this
      study was to evaluate the effect of methimazole-induced hypothyreosis on
      oxidative stress secondary to doxorubicin administration. 48 hours after
      methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15
      mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug
      administration. Animals exposed exclusively to doxorubicin or untreated ones were
      also assessed. The hypothyreosis (0.025% of methimazole) significantly increased
      the doxorubicin effect on the cardiac carbonyl group and they may increase the
      glutathione level. An insignificant effect of methimazole was noticed in case of
      the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS
      and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin.
      However, the concentration of P450R was affected by a lower dose of methimazole
      in rats administered with doxorubicin. Since in rats receiving doxorubicin
      changes in oxidative stress caused by methimazole were not accompanied by
      elevation of bioreductive enzymes, it may be concluded that these changes in the
      oxidative stress were not related to the tested enzymes.

PMID- 22966414
TI  - Impact of oral ubiquinol on blood oxidative stress and exercise performance.
AB  - Coenzyme Q10 (CoQ10) plays an important role in bioenergetic processes and has
      antioxidant activity. Fifteen exercise-trained individuals (10 men and 5 women;
      30-65 years) received reduced CoQ10 (Kaneka QH ubiquinol; 300 mg per day) or a
      placebo for four weeks in a random order, double blind, cross-over design (3 week
      washout). After each four-week period, a graded exercise treadmill test and a
      repeated cycle sprint test were performed (separated by 48 hours). Blood samples
      were collected before and immediately following both exercise tests and analyzed
      for lactate, malondialdehyde, and hydrogen peroxide. Resting blood samples were
      analyzed for CoQ10 (ubiquinone and ubiquinol) profile before and after each
      treatment period. Treatment with CoQ10 resulted in a significant increase in
      total blood CoQ10 (138%; P = 0.02) and reduced blood CoQ10 (168%; P = 0.02), but
      did not improve exercise performance (with the exception of selected individuals)
      or impact oxidative stress. The relationship between the percentage change in
      total blood CoQ10 and the cycle sprint total work (R(2) = 0.6009) was noted to be
      moderate to strong. We conclude that treatment with CoQ10 in healthy, exercise
      trained subjects increases total and reduced blood CoQ10, but this increase does
      not translate into improved exercise performance or decreased oxidative stress.

PMID- 22966415
TI  - Riluzole-triggered GSH synthesis via activation of glutamate transporters to
      antagonize methylmercury-induced oxidative stress in rat cerebral cortex.
AB  - OBJECTIVE: This study was to evaluate the effect of riluzole on methylmercury-
      (MeHg-) induced oxidative stress, through promotion of glutathione (GSH)
      synthesis by activating of glutamate transporters (GluTs) in rat cerebral cortex.
      METHODS: Eighty rats were randomly assigned to four groups, control group,
      riluzole alone group, MeHg alone group, and riluzole + MeHg group. The
      neurotoxicity of MeHg was observed by measuring mercury (Hg) absorption,
      pathological changes, and cell apoptosis of cortex. Oxidative stress was
      evaluated via determining reactive oxygen species (ROS), 8-hydroxy-2
      deoxyguanosine (8-OHdG), malondialdehyde (MDAs), carbonyl, sulfydryl, and GSH in
      cortex. Glutamate (Glu) transport was studied by measuring Glu, glutamine (Gln),
      mRNA, and protein of glutamate/aspartate transporter (GLAST) and glutamate
      transporter-1 (GLT-1). RESULT: (1) MeHg induced Hg accumulation, pathological
      injury, and apoptosis of cortex; (2) MeHg increased ROS, 8-OHdG, MDA, and
      carbonyl, and inhibited sulfydryl and GSH; (3) MeHg elevated Glu, decreased Gln,
      and downregulated GLAST and GLT-1 mRNA expression and protein levels; (4)
      riluzole antagonized MeHg-induced downregulation of GLAST and GLT-1 function and
      expression, GSH depletion, oxidative stress, pathological injury, and apoptosis
      obviously. CONCLUSION: Data indicate that MeHg administration induced oxidative
      stress in cortex and that riluzole could antagonize this situation through
      elevation of GSH synthesis by activating of GluTs.

PMID- 22966416
TI  - ROS in aging Caenorhabditis elegans: damage or signaling?
AB  - Many insights into the mechanisms and signaling pathways underlying aging have
      resulted from research on the nematode Caenorhabditis elegans. In this paper, we
      discuss the recent findings that emerged using this model organism concerning the
      role of reactive oxygen species (ROS) in the aging process. The accrual of
      oxidative stress and damage has been the predominant mechanistic explanation for
      the process of aging for many years, but reviewing the recent studies in C.
      elegans calls this theory into question. Thus, it becomes more and more evident
      that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it
      seems more likely that tightly controlled concentrations of ROS and fluctuations
      in redox potential are important mediators of signaling processes. We therefore
      discuss some theories that explain how redox signaling may be involved in aging
      and provide some examples of ROS functions and signaling in C. elegans
      metabolism. To understand the role of ROS and the redox status in physiology,
      stress response, development, and aging, there is a rising need for accurate and
      reversible in vivo detection. Therefore, we comment on some methods of ROS and
      redox detection with emphasis on the implementation of genetically encoded
      biosensors in C. elegans.

PMID- 22966418
TI  - The fate of a normal human cell traversed by a single charged particle.
AB  - The long-term "fate" of normal human cells after single hits of charged particles
      is one of the oldest unsolved issues in radiation protection and cellular
      radiobiology. Using a high-precision heavy-ion microbeam we could target normal
      human fibroblasts with exactly one or five carbon ions and measured the early
      cytogenetic damage and the late behaviour using single-cell cloning. Around 70%
      of the first cycle cells presented visible aberrations in mFISH after a single
      ion traversal, and about 5% of the cells were still able to form colonies. In one
      third of selected high-proliferative colonies we observed clonal (radiation
      induced) aberrations. Terminal differentiation and markers of senescence (PCNA,
      p16) in the descendants of cells traversed by one carbon ion occurred earlier
      than in controls, but no evidence of radiation-induced chromosomal instability
      was found. We conclude that cells surviving single-ion traversal, often carrying
      clonal chromosome aberrations, undergo accelerated senescence but maintain
      chromosomal stability.

PMID- 22966419
TI  - Identifying states of a financial market.
AB  - The understanding of complex systems has become a central issue because such
      systems exist in a wide range of scientific disciplines. We here focus on
      financial markets as an example of a complex system. In particular we analyze
      financial data from the S&P 500 stocks in the 19-year period 1992-2010. We
      propose a definition of state for a financial market and use it to identify
      points of drastic change in the correlation structure. These points are mapped to
      occurrences of financial crises. We find that a wide variety of characteristic
      correlation structure patterns exist in the observation time window, and that
      these characteristic correlation structure patterns can be classified into
      several typical "market states". Using this classification we recognize
      transitions between different market states. A similarity measure we develop thus
      affords means of understanding changes in states and of recognizing developments
      not previously seen.

PMID- 22966420
TI  - Dynamical Autler-Townes control of a phase qubit.
AB  - Routers, switches, and repeaters are essential components of modern information
      processing systems. Similar devices will be needed in future superconducting
      quantum computers. In this work we investigate experimentally the time evolution
      of Autler-Townes splitting in a superconducting phase qubit under the application
      of a control tone resonantly coupled to the second transition. A three-level
      model that includes independently determined parameters for relaxation and
      dephasing gives excellent agreement with the experiment. The results demonstrate
      that the qubit can be used as a ON/OFF switch with 100 ns operating time-scale
      for the reflection/transmission of photons coming from an applied probe microwave
      tone. The ON state is realized when the control tone is sufficiently strong to
      generate an Autler-Townes doublet, suppressing the absorption of the probe tone
      photons and resulting in a maximum of transmission.

PMID- 22966417
TI  - Lung oxidative damage by hypoxia.
AB  - One of the most important functions of lungs is to maintain an adequate
      oxygenation in the organism. This organ can be affected by hypoxia facing both
      physiological and pathological situations. Exposure to this condition favors the
      increase of reactive oxygen species from mitochondria, as from NADPH oxidase,
      xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as
      establishing an inflammatory process. In lungs, hypoxia also modifies the levels
      of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox
      state in lungs induced by hypoxia has been suggested as a participant in the
      changes observed in lung function in the hypoxic context, such as hypoxic
      vasoconstriction and pulmonary edema, in addition to vascular remodeling and
      chronic pulmonary hypertension. In this work, experimental evidence that shows
      the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein,
      studies of cultures of different lung cells and complete isolated lung and tests
      conducted in vivo in the different forms of hypoxia, conducted in both animal
      models and humans, are described.

PMID- 22966421
TI  - Evolution of cooperation driven by zealots.
AB  - Recent experimental results with humans involved in social dilemma games suggest
      that cooperation may be a contagious phenomenon and that the selection pressure
      operating on evolutionary dynamics (i.e., mimicry) is relatively weak. I propose
      an evolutionary dynamics model that links these experimental findings and
      evolution of cooperation. By assuming a small fraction of (imperfect) zealous
      cooperators, I show that a large fraction of cooperation emerges in evolutionary
      dynamics of social dilemma games. Even if defection is more lucrative than
      cooperation for most individuals, they often mimic cooperation of fellows unless
      the selection pressure is very strong. Then, zealous cooperators can transform
      the population to be even fully cooperative under standard evolutionary dynamics.

PMID- 22966422
TI  - Changes in heart rate variability of depressed patients after electroconvulsive
      therapy.
AB  - Objective. As few, small studies have examined the impact of electroconvulsive
      therapy (ECT) upon the heart rate variability of patients with major depressive
      disorder (MDD), we sought to confirm whether ECT-associated improvement in
      depressive symptoms would be associated with increases in HRV linear and
      nonlinear parameters. Methods. After providing consent, depressed study
      participants (n = 21) completed the Beck Depression Index (BDI), and 15-minute
      Holter monitor recordings, prior to their 1st and 6th ECT treatments. Holter
      recordings were analyzed for certain HRV indices: root mean square of successive
      differences (RMSSD), low-frequency component (LF)/high-frequency component (HF)
      and short-(SD1) versus long-term (SD2) HRV ratios. Results. There were no
      significant differences in the HRV indices of RMSDD, LF/HF, and SD1/SD2 between
      the patients who responded, and those who did not, to ECT. Conclusion. In the
      short term, there appear to be no significant improvement in HRV in ECT-treated
      patients whose depressive symptoms respond versus those who do not. Future
      studies will reveal whether diminished depressive symptoms with ECT are reliably
      associated with improved sympathetic/parasympathetic balance over the long-term,
      and whether acute changes in sympathetic/parasympathetic balance predict improved
      mental- and cardiac-related outcomes.

PMID- 22966423
TI  - A two-piece derivative of a group I intron RNA as a platform for designing self
      assembling RNA templates to promote Peptide ligation.
AB  - Multicomponent RNA-peptide complexes are attractive from the viewpoint of
      artificial design of functional biomacromolecular systems. We have developed self
      folding and self-assembling RNAs that serve as templates to assist chemical
      ligation between two reactive peptides with RNA-binding capabilities. The design
      principle of previous templates, however, can be applied only to limited classes
      of RNA-binding peptides. In this study, we employed a two-piece derivative of a
      group I intron RNA from the Tetrahymena large subunit ribosomal RNA (LSU rRNA) as
      a platform for new template RNAs. In this group I intron-based self-assembling
      platform, modules for the recognition of substrate peptides can be installed
      independently from modules holding the platform structure. The new self
      assembling platform allows us to expand the repertoire of substrate peptides in
      template RNA design.

PMID- 22966424
TI  - The Role of M. leprae Hsp65 Protein and Peptides in the Pathogenesis of Uveitis.
AB  - Experimental autoimmune uveitis (EAU) is a well established model for immune
      mediated organ-specific disease. Our group has recently shown that the M. leprae
      Hsp65 aggravated the uveitis in mice; in the present study, we evaluated the
      action of M. leprae  K(409)A mutant protein and the synthetic peptides Leader pep
      and K(409)A pep (covering amino acids residues 352-371 of WT and K(409)A proteins
      of M. leprae Hsp65, resp.) on the pathogenesis of EAU. Mice received the 161-180
      IRBP peptide and B. pertussis toxin followed by the intraperitoneal inoculation
      of K(409)A protein or the Leader pep or K(409)A pep. The Leader pep aggravated
      the disease, but mice receiving the K(409)A pep did not develop the disease and
      presented an increase in IL-10 levels by spleen cells and a decrease in the
      percentage of CD4+ IFN-gamma+ T cells. Moreover, animals receiving the Leader pep
      presented the highest scores of the disease associated with increase percentage
      of CD4+ IFN-gamma+ T cells. These results would contribute to understanding of
      the pathogenesis of EAU and support the concept that immune responses to Hsp are
      of potential importance in exacerbating, perpetuating, or even controlling organ
      restricted autoimmune diseases, and it is discussed the irreversibility of
      autoimmune syndromes.

PMID- 22966425
TI  - Assessing the Association between Leptin and Bone Mineral Density in HIV-Infected
      Men.
AB  - HIV-infected individuals are at risk for decreased bone mineral density (BMD).
      The known risk factors for bone loss do not fully explain the increased risk in
      this population. There is emerging evidence that leptin, a hormone secreted by
      adipocytes, plays an important role in bone metabolism. Several studies have
      assessed the relationship between leptin and bone density in healthy adults, but
      there are few such studies in HIV-infected individuals. Furthermore, HIV infected
      individuals on antiretroviral therapy are at increased risk for altered fat
      distribution, which may impact the relationship between leptin and BMD. In a
      cross-sectional analysis of data in 107 HIV-infected men, we determined whether
      serum leptin levels were associated with whole-body BMD and bone mineral content
      measured by dual-energy X-ray absorptiometry (DEXA), after adjusting for
      confounders including body fat distribution. We found an inverse association
      between leptin and bone density in those with peripheral lipoatrophy, defined
      objectively as <3 kg appendicular fat by DEXA, but no such relationship was seen
      in those with >3 kg appendicular fat. This result suggests that fat distribution
      may modify the relationship between leptin and bone density.

PMID- 22966426
TI  - Rapid Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in HIV-Infected
      Patients. Comparison of LED Fluorescent Microscopy and the GeneXpert MTB/RIF
      Assay in a District Hospital in India.
AB  - HIV-related tuberculosis is difficult to diagnose and is associated with high
      morbidity and mortality. Recently, the World Health Organization has endorsed the
      GeneXpert MTB/RIF (Xpert) assay for the diagnosis of pulmonary tuberculosis in
      HIV-infected patients from developing countries, but information about the use of
      Xpert for the diagnosis of extrapulmonary tuberculosis is scarce. In this study,
      we compared the performance of light-emitting diode (LED) auramine fluorescent
      microscopy and the Xpert assay for the diagnosis of tuberculosis in HIV infected
      patients in a district hospital of India. Although at higher cost, Xpert
      outperformed LED fluorescent microscopy in all type of specimens, especially in
      cerebrospinal fluid where the number of positive results was increased 11 times.
      Pleural fluid, ascitic fluid, pus, and stool specimens also yielded positive
      results with the Xpert assay. When collecting two additional early-morning sputum
      samples, the increase of the number of positive results with the Xpert assay was
      lower than previously reported for HIV infected patients. Rifampicin resistance
      was observed in 2.2% of the cases. The results of this study show that the Xpert
      assay can dramatically improve the rapid diagnosis of tuberculous meningitis and
      other types of extrapulmonary tuberculosis of HIV infected patients.

PMID- 22966427
TI  - Lumbar facet joint compressive injury induces lasting changes in local structure,
      nociceptive scores, and inflammatory mediators in a novel rat model.
AB  - Objective. To develop a novel animal model of persisting lumbar facet joint pain.
      Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6)
      facet joint was exposed and compressed to ~1 mm with modified clamps applied for
      three minutes; sham-operated and naive animals were used as control groups. After
      five days, animals were tested for hind-paw sensitivity using von Frey filaments
      and axial deep tissue sensitivity by algometer on assigned days up to 28 days.
      Animals were sacrificed at selected times for histological and biochemical
      analysis. Results. Histological sections revealed site-specific loss of cartilage
      in model animals only. Tactile hypersensitivity was observed for the ipsi- and
      contralateral paws lasting 28 days. The threshold at which deep tissue pressure
      just elicited vocalization was obtained at three lumbar levels; sensitivity at L1
      > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory
      cytokines, especially TNF-alpha, IL-1alpha, and IL-1beta. Conclusions. These data
      suggest that compression of a facet joint induces a novel model of local
      cartilage loss accompanied by increased sensitivity to mechanical stimuli and by
      increases in inflammatory mediators. This new model may be useful for studies on
      mechanisms and treatment of lumbar facet joint pain and osteoarthritis.

PMID- 22966428
TI  - Parents' initial perceptions of multidisciplinary care for pediatric chronic
      pain.
AB  - Chronic and recurrent pain is experienced by many children and adolescents.
      Treatment of chronic pain using a multidisciplinary approach has been found to be
      effective for treatment of chronic pain. Parent satisfaction with treatment and
      treatment providers highly correlates to children's treatment adherence. Parents
      of children treated at a multidisciplinary chronic pain clinic were interviewed
      following their initial appointment. Parents reported high satisfaction with
      treatment team members and with the treatment plan. Parents also reported
      appreciation of multidisciplinary structure, the high level of expertise of the
      team members, and the team members' genuine interest in treating their children.
      This increase in satisfaction when compared to previous treatment is important
      since increases in satisfaction may correlate with a reduction in experiences of
      chronic pain. Parents reported high satisfaction with interactions with treatment
      team members and with the treatment plan provided for their children. Parents had
      appreciation of multidisciplinary team structure and the high level of expertise
      of the team members. This increase in satisfaction when compared to treatment
      from previous providers is important since increases in satisfaction may
      correlate with an increase in children's treatment adherence and a reduction in
      experiences of chronic pain.

PMID- 22966429
TI  - Novel insights of oligometastases and oligo-recurrence and review of the
      literature.
AB  - Oligometastases and oligo-recurrence are among the most important notions of
      metastatic and recurrent cancer. The concept of oligometastases is related to the
      notion that cancer patients with 1-5 metastatic or recurrent lesions that could
      be treated by local therapy achieve long-term survival or cure, while the concept
      of oligo-recurrence is related to the notion that cancer patients with 1-5
      metastatic or recurrent lesions that could be treated by local therapy have
      controlled primary lesions. Achievement of long-term survival or cure in patients
      with oligometastases and oligo-recurrence is cancer and organ specific. These
      facts rely on the seed and soil theory and multiple steps of cancer progression.
      Oligo-recurrence is considered to have a better prognosis than oligometastases.
      In patients with oligometastases and oligo-recurrence, the oligometastases and
      oligo-recurrence are sometimes cured with only local therapy, which is an example
      of the abscopal effect, previously described in relation to cure of lesions
      outside of the field of radiation therapy without systemic therapy.
      Oligometastases and oligo-recurrence can now be cured by less invasive local
      treatment methods combined with systemic therapy. The mechanisms of
      oligometastases and oligo-recurrence, as well as novel insights into these
      important concepts, are presented in this paper.

PMID- 22966431
TI  - Loss of asthma control in pediatric patients after discontinuation of long-acting
      Beta-agonists.
AB  - Recent asthma recommendations advocate the use of long-acting beta-agonists
      (LABAs) in uncontrolled asthma, but also stress the importance of stepping down
      this therapy once asthma control has been achieved. The objective of this study
      was to evaluate downtitration of LABA therapy in pediatric patients who are well
      controlled on combination-inhaled corticosteroid (ICS)/LABA therapy. Clinical and
      physiologic outcomes were studied in children with moderate-to-severe persistent
      asthma after switching from combination (ICS/LABA) to monotherapy with ICS. Of
      the 54 patients, 34 (63%) were determined to have stable asthma after the switch,
      with a mean followup of 10.7 weeks. Twenty (37%) had loss of asthma control
      leading to addition of leukotriene receptor antagonists, increased ICS, or
      restarting LABA. There were 2 exacerbations requiring treatment with systemic
      steroids. In patients with loss of control, there was a statistically significant
      decline in FEV(1) (-8% versus -1.9%, P = 0.03) and asthma control test (-3.2
      versus -0.5, P = 0.03). This did not approach significance for FEF(25-75%),
      exhaled nitric oxide, lung volumes or airway reactivity. No demographic, asthma
      control measures, or lung function variables predicted loss of control. Pediatric
      patients with moderate-to-severe persistent asthma who discontinue LABA therapy
      have a 37% chance of losing asthma control resulting in augmented maintenance
      therapies. Recent recommendations of discontinuing LABA therapy as soon as
      control is achieved should be evaluated in a prospective long-term study.

PMID- 22966430
TI  - Virus infection-induced bronchial asthma exacerbation.
AB  - Infection with respiratory viruses, including rhinoviruses, influenza virus, and
      respiratory syncytial virus, exacerbates asthma, which is associated with
      processes such as airway inflammation, airway hyperresponsiveness, and mucus
      hypersecretion. In patients with viral infections and with infection-induced
      asthma exacerbation, inflammatory mediators and substances, including
      interleukins (ILs), leukotrienes and histamine, have been identified in the
      airway secretions, serum, plasma, and urine. Viral infections induce an
      accumulation of inflammatory cells in the airway mucosa and submucosa, including
      neutrophils, lymphocytes and eosinophils. Viral infections also enhance the
      production of inflammatory mediators and substances in airway epithelial cells,
      mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF,
      RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect
      the barrier function of the airway epithelial cells and vascular endothelial
      cells. Recent reports have demonstrated augmented viral production mediated by an
      impaired interferon response in the airway epithelial cells of asthma patients.
      Several drugs used for the treatment of bronchial asthma reduce viral and pro
      inflammatory cytokine release from airway epithelial cells infected with viruses.
      Here, I review the literature on the pathogenesis of the viral infection-induced
      exacerbation of asthma and on the modulation of viral infection-induced airway
      inflammation.

PMID- 22966432
TI  - Faulty suppression of irrelevant material in patients with thought disorder
      linked to attenuated frontotemporal activation.
AB  - Formal thought disorder is a feature schizophrenia that manifests as
      disorganized, incoherent speech, and is associated with a poor clinical outcome.
      The neurocognitive basis of this symptom is unclear but it is thought to involve
      an impairment in semantic processing classically described as a loosening of
      meaningful associations. Using a paradigm derived from the n400 event-related,
      potential, we examined the extent to which regional activation during semantic
      processing is altered in schizophrenic patients with formal thought disorder. Ten
      healthy control and 18 schizophrenic participants (9 with and 9 without formal
      thought disorder) performed a semantic decision sentence task during an event
      related functional magnetic resonance imaging experiment. We employed analysis of
      variance to estimate the main effects of semantic congruency and groups on
      activation and specific effects of formal thought disorder were addressed using
      post-hoc comparisons. We found that the frontotemporal network, normally engaged
      by a semantic decision task, was underactivated in schizophrenia, particularly in
      patients with FTD. This network is implicated in the inhibition of automatically
      primed stimuli and impairment of its function interferes with language processing
      and contributes to the production of incoherent speech.

PMID- 22966433
TI  - Long-acting injectable antipsychotics in first-episode schizophrenia.

PMID- 22966434
TI  - Gender differences in service use in a sample of people with schizophrenia and
      other psychoses.
AB  - Objective. The main objective is to analyze the use of mental health services in
      a sample of people with schizophrenia and other psychoses according to gender.
      Method. The sample of this observational and retrospective study (n = 7483)
      consisted of all the persons who visited any mental health service of the Parc
      Sanitari Sant Joan de Deu from 2001 to 2007 with a diagnosis of schizophrenia and
      other psychoses. The main measures analyzed regarding gender were the frequency
      of patients for each diagnosis, their risk of being admitted into hospital, and
      the number and length of hospitalizations for the subsample of inpatient people
      during the study period. Results. Men are more frequent in the total sample
      (58.1%). For diagnosis of schizoaffective or delusional disorder, women have a
      higher frequency than men. Women with diagnosis of schizophrenia have a lower
      risk of being admitted to the hospital (RR = 0.84, 95% CI (0.72, 0.97)). We found
      a higher risk of longer stays for men with schizophrenia of the disorganized type
      (RR = 0.49, 95% CI (0.30, 0.81)), undifferentiated (RR = 0.41, 95% CI (0.27,
      0.61)), or delusional disorder (RR = 0.65, 95% CI (0.49, 0.87)). Conclusion.
      Gender of patients is a relevant variable in mental health service use by
      patients with schizophrenia and other psychoses.

PMID- 22966435
TI  - Treatment adherence with early prescription of long-acting injectable
      antipsychotics in recent-onset schizophrenia.
AB  - Although response to treatment for the first episode of schizophrenia is
      generally favourable, nonadherence with the treatment is the first cause of
      relapse and rehospitalisation within the next few years. Long-acting injectable
      antipsychotics (LAIAs) combine the advantages of the newer antipsychotics and the
      long-acting formulation. The evaluation concerns 25 schizophrenic patients
      hospitalised for the first time, treated with risperidone long-acting injectable
      (RLAI) associated with reintegration methods, and followed up for at least 18
      months. Clinical observation was completed using Clinical Global Impression (CGI)
      scale and Global Assessment of Functioning (GAF). Clinical improvement was
      coupled with a good reintegration rate, very few relapse, or rehospitalisation.
      Bimonthly injection combined with psychosocial methods improved interactive
      followup, and therefore patients' compliance with the treatment. Treating with
      LAIA as early as possible, from the first episode if possible, can reduce
      relapse, number and duration of rehospitalisation, and cognitive symptoms and
      improve the quality of life and prognosis.

PMID- 22966436
TI  - Oral versus Long-Acting Injectable Antipsychotics in the Treatment of
      Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A
      Systematic Review.
AB  - Long-acting injectable antipsychotics (LAIs) should offer better efficacy and
      tolerability, compared to oral antipsychotics due to improved adherence and more
      stable pharmacokinetics. However, data on LAIs has been mixed, with some studies
      finding that they are more effective and tolerable than oral antipsychotics, and
      others finding the contrary. One possibility for the disparate results may be
      that some studies administered different antipsychotics in the oral and
      injectable form. The present systematic review examined the efficacy and
      tolerability of LAIs versus their oral equivalents in randomized and naturalistic
      studies. In addition, it examined the impact of LAIs on special populations such
      as patients with first-episode psychosis, substance use disorders, and a history
      of violence or on involuntary outpatient commitment. Randomized studies suggest
      that not all LAIs are the same; for example, long-acting risperidone may be
      associated with equal or less side effects than oral risperidone, whereas
      fluphenazine decanoate and enanthate may be associated with equal or more side
      effects than oral fluphenazine. They also suggest that LAIs reduce risk of
      relapse versus oral antipsychotics in schizophrenia outpatients when combined
      with quality psychosocial interventions. For their part, naturalistic studies
      point to a larger magnitude of benefit for LAIs, relative to their oral
      equivalents particularly among first-episode patients.

PMID- 22966437
TI  - From semantics to feelings: how do individuals with schizophrenia rate the
      emotional valence of words?
AB  - Schizophrenia is characterized by both emotional and language abnormalities.
      However, in spite of reports of preserved evaluation of valence of affective
      stimuli, such as pictures, it is less clear how individuals with schizophrenia
      assess verbal material with emotional valence, for example, the overall
      unpleasantness/displeasure relative to pleasantness/attraction of a word. This
      study aimed to investigate how schizophrenic individuals rate the emotional
      valence of adjectives, when compared with a group of healthy controls. One
      hundred and eighty-four adjectives differing in valence were presented. These
      adjectives were previously categorized as "neutral," "positive" (pleasant), or
      "negative" (unpleasant) by five judges not participating in the current
      experiment. Adjectives from the three categories were matched on word length,
      frequency, and familiarity. Sixteen individuals with schizophrenia diagnosis and
      seventeen healthy controls were asked to rate the valence of each word, by using
      a computerized version of the Self-Assessment Manikin (Bradley and Lang, 1994).
      Results demonstrated similar ratings of emotional valence of words, suggesting a
      similar representation of affective knowledge in schizophrenia, at least in terms
      of the valence dimension.

PMID- 22966438
TI  - The role of oestrogen and other hormones in the pathophysiology and treatment of
      schizophrenia.
AB  - The theory that many serious mental illnesses, in particular psychoses such as
      schizophrenia, may have a significant hormonal aetiological component is fast
      gaining popularity and the support of scientific evidence. Oestrogen in
      particular has been substantially investigated as a potential mediator of brain
      function in schizophrenia. Epidemiological and life-cycle data point to
      significant differences in the incidence and course of schizophrenia between men
      and women suggests a protective role of oestrogen. In vitro and in vivo
      preclinical research confirms oestradiol's interactions with central
      neurotransmitter systems implicated in the pathogenesis of schizophrenia, while
      results from randomised controlled trials investigating the antipsychotic
      potential of oestrogen have been positive. Research into other neuroactive
      hormones with possible effects on mental state is a rapidly evolving field that
      may hold new promise. Given that schizophrenia and related psychoses are
      pervasive and debilitating conditions for which currently available treatments
      are often only partially effective and entail a high risk of serious side
      effects, novel therapeutic strategies are needed. The literature reviewed in this
      paper suggests that hormones such as oestrogen could be a viable option, and it
      is hoped that with further research and larger trials, the oestrogen hypothesis
      can be translated into effective clinical practice.

PMID- 22966439
TI  - Long-acting injectable antipsychotics for first-episode schizophrenia: the pros
      and cons.
AB  - Clinical and psychosocial deterioration associated with schizophrenia occurs
      within the first few years following the onset of the illness. Therefore, to
      improve the long-term prognosis, it is important to provide schizophrenia
      patients with intensive treatment following their first episode. Relapse is
      highly associated with partial medication adherence or nonadherence in patients
      with first-episode schizophrenia. Recent studies suggest that long-acting
      injectable (LAI) antipsychotics compared with oral antipsychotics are more
      effective for medication adherence and relapse prevention. Moreover, some
      clinical guidelines for the treatment of schizophrenia suggested that LAI
      antipsychotics should be considered when patients are nonadherent "at any stage."
      Decreased compliance is a common cause of relapse during the initial stages of
      the disease. Therefore, LAI antipsychotics should be highly considered when
      treating patients with first-episode schizophrenia. In the present paper,
      clinical trial data and current guidelines on the use of LAI antipsychotics for
      first-episode schizophrenia are discussed as well as the pros and cons of this
      treatment option.

PMID- 22966440
TI  - Gender differences in remission and recovery of schizophrenic and schizoaffective
      patients: preliminary results of a prospective cohort study.
AB  - The aim of the paper was to evaluate rates of clinical remission and recovery
      according to gender in a cohort of chronic outpatients attending a university
      community mental health center who had been diagnosed with schizophrenia and
      schizoaffective disorder according to DSM-IV-TR. A sample of 100 consecutive
      outpatients (70 males and 30 females) underwent comprehensive psychiatric
      evaluation using the Structured Clinical Interview for Diagnosis of Axis I and II
      DSM-IV (SCID-I and SCID-II, Version R) and an assessment of psychopathology,
      social functioning, clinical severity, subjective wellbeing, and quality of life,
      respectively by means of PANSS (Positive and Negative Syndrome Scale), PSP
      (Personal and Social Performance), CGI-SCH (Clinical Global Impression
      Schizophrenia scale), SWN-S (Subjective Well-being under Neuroleptics-scale), and
      WHOQOL (WHO Quality of Life). Rates of clinical remission and recovery according
      to different criteria were calculated by gender. Higher rates of clinical
      remission and recovery were generally observed in females than males, a result
      consistent with literature data. Overall findings from the paper support the
      hypothesis of a better outcome of the disorders in women, even in the very long
      term.

PMID- 22966441
TI  - Where Does Evidence from New Trials for Schizophrenia Fit with the Existing
      Evidence: A Case of the Emperor's New Clothes?
AB  - Advent of "atypical" antipsychotics has spawned new trials in the recent years
      and the number of such trial reports has been increasing exponentially. As
      clinicians we have been led to believe that "atypicals" are better than
      "typicals" despite the odd dissenting voice in academic and clinical circles.
      This has been largely ignored until the publication of two landmark, independent,
      pragmatic trials, Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) and Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study
      (CUtLASS), which proved that thoughtfully chosen "typical" antipsychotics were as
      good as the newer "atypicals." We pooled "leaving the study early data" from
      Cochrane Reviews that existed before CATIE and CUtLASS and added data from CATIE
      and CUtLASS to the pool for a "before and after" comparison. Addition of CATIE
      and CUtLASS data only led to narrowing of the already existing confidence
      intervals, merely increasing precision, and decreasing the risk of Type II error.
      Perhaps surprisingly, CATIE and CUtLASS when pooled with the already existing
      data showed us that we had chosen to turn a blind eye to findings that already
      existed. This leads clinicians to question as to whether, in future, we need to
      feel less guilty about crying out early on that the emperor has no clothes on.

PMID- 22966442
TI  - Psychosis and gender.

PMID- 22966443
TI  - Examining the factors associated with paid employment of clients enrolled in
      first episode of psychosis programs.
AB  - Schizophrenia is one of the most debilitating mental disorders. For a significant
      portion of individuals who suffer from this disorder, onset occurs in young
      adulthood, arresting important social and educational development that is
      necessary for future successful labor force participation. The purpose of this
      paper is to contribute to the literature about clients enrolled in first episode
      psychosis programs and psychosocial outcomes by examining the factors associated
      with paid employment among young adults who have experienced their first
      psychotic episodes. In this paper, we consider the association of socioeconomic
      factors to employment. Our results suggest that in addition to treatment,
      socioeconomic factors such as receipt of public disability benefits and
      educational attainment are associated with employment status. These results can
      help to inform future directions for the enhancement of psychosocial programs in
      FEP models to promote paid employment.

PMID- 22966444
TI  - Role of long-acting injectable second-generation antipsychotics in the treatment
      of first-episode schizophrenia: a clinical perspective.
AB  - Approximately 80% of patients with the first-episode schizophrenia reach
      symptomatic remission after antipsychotic therapy. However, within two years most
      of them relapse, mainly due to low levels of insight into the illness and
      nonadherence to their oral medication. Therefore, although the formal data
      available is limited, many experts recommend prescribing long-acting injectable
      second-generation antipsychotics (mostly risperidone or alternatively
      paliperidone) in the early stages of schizophrenia, particularly in patients who
      have benefited from the original oral molecule in the past and agree to receive
      long-term injectable treatment. Early application of long-acting injectable
      second-generation antipsychotics can significantly reduce the risk of relapse in
      the future and thus improve not only the social and working potential of patients
      with schizophrenia but also their quality of life.

PMID- 22966445
TI  - Hospitalisation Utilisation and Costs in Schizophrenia Patients in Finland before
      and after Initiation of Risperidone Long-Acting Injection.
AB  - Objectives. Quantify changes in hospital resource use in Finland following
      initiation of risperidone long-acting injection (RLAI). Materials and Methods. A
      retrospective multi-center chart review (naturalistic setting) was used to
      compare annual hospital bed-days and hospital episodes for 177 schizophrenia
      patients (mean age 47.1 years, 52% female, 72% hospitalized) before and after
      initiation of RLAI (between January 2004 and June 2005) using the within-patient
      "mirror-image" study design. The base case analytical approach allocated hospital
      episodes overlapping the start date entirely to the preinitiation period. In
      order to investigate the impact of inpatient care ongoing at baseline, the change
      in bed-days was also estimated using an alternative analytical approached related
      to economic modelling. Results. In the conventional analysis, the mean annual
      hospitalisation costs declined by ?11,900 and the number of bed-days was reduced
      by 40%, corresponding to 0.19 fewer hospital episodes per year. The reductions in
      bed-days per patient-year were similar for patients switched to RLAI as
      inpatients and as outpatients. In the modelling-based analysis, an 8% reduction
      in bed-days per year was observed. Conclusion. Despite uncertainty in the choice
      of analytic approach for allocating inpatient episodes that overlapping this
      initiation, consistent reductions in resource use are associated with the
      initiation of RLAI in Finland.

PMID- 22966446
TI  - Intervention to prevent child custody loss in mothers with schizophrenia.
AB  - Depending on jurisdiction, time period studied, and specifics of the population,
      approximately 50 percent of mothers who suffer from schizophrenia lose custody of
      their children. The aim of this paper is to recommend interventions aimed at
      preventing unnecessary custody loss. This paper reviews the social work, nursing,
      psychology, psychiatry, and law literature on mental illness and custody loss,
      2000-2011. Recommendations to mothers are to (a) ensure family health (b) prevent
      psychotic relapse, (c) prepare in advance for crisis, (d) document daily
      parenting activities, (e) take advantage of available parenting resources, and f)
      become knowledgeable about legal issues that pertain to mental health and
      custody. From a policy perspective, child protection and adult mental health
      agencies need to dissolve administrative barriers and collaborate. Access to
      appropriate services will help mothers with schizophrenia to care appropriately
      for their children and allow these children to grow and develop within their
      family and community.

PMID- 22966448
TI  - The PPARalpha Agonist Fenofibrate Reduces Prepulse Inhibition Disruption in a
      Neurodevelopmental Model of Schizophrenia.
AB  - Oxidative stress has been implicated in neurodevelopmental theories of
      schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors alpha
      (PPARalpha) agonist fenofibrate has neuroprotective properties and could reverse
      early preclinical infringements that could trigger the illness. We have evaluated
      the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of
      schizophrenia. The oxidative lesion induced by Kainic Acid (KA) injection at
      postnatal day (PND) 7 has previously been reported to disrupt Prepulse Inhibition
      (PPI) at PND56 but not at PND35. In 4 groups of 15 male rats each, KN (KA-PND7 +
      normal postweaning food), KF (KA-PND7 + fenofibrate 0.2% food), ON (saline-PND7 +
      normal food), and OF (saline + fenofibrate food), PPI was recorded at PND35 and
      PND56. Three levels of prepulse were used: 73 dB, 76 dB, and 82 dB for a pulse at
      120 dB. Four PPI scores were analyzed: PPI73, PPI76, PPI82, and mean PPI (PPIm).
      Two-way ANOVAs were used to evaluate the effects of both factors (KA +
      fenofibrate), and, in case of significant results, intergroup Student's t-tests
      were performed. We notably found a significant difference (P < 0.05) in PPIm
      between groups KN and KF at PND56, which supposes that fenofibrate could be
      worthy of interest for early neuroprotection in schizophrenia.

PMID- 22966449
TI  - Stability of facial affective expressions in schizophrenia.
AB  - Thirty-two videorecorded interviews were conducted by two interviewers with eight
      patients diagnosed with schizophrenia. Each patient was interviewed four times:
      three weekly interviews by the first interviewer and one additional interview by
      the second interviewer. 64 selected sequences where the patients were speaking
      about psychotic experiences were scored for facial affective behaviour with
      Emotion Facial Action Coding System (EMFACS). In accordance with previous
      research, the results show that patients diagnosed with schizophrenia express
      negative facial affectivity. Facial affective behaviour seems not to be dependent
      on temporality, since within-subjects ANOVA revealed no substantial changes in
      the amount of affects displayed across the weekly interview occasions. Whereas
      previous findings found contempt to be the most frequent affect in patients, in
      the present material disgust was as common, but depended on the interviewer. The
      results suggest that facial affectivity in these patients is primarily dominated
      by the negative emotions of disgust and, to a lesser extent, contempt and implies
      that this seems to be a fairly stable feature.

PMID- 22966450
TI  - The psychotomimetic nature of dreams: an experimental study.
AB  - Several theories promote the similarities between dreaming and psychosis, but
      this has rarely been tested empirically. We assessed dreaming and waking reality
      using the Psychotomimetic States Inventory, a measure of psychotic-like
      experience originally designed for drug studies. Twenty participants completed
      the measure in each of two dream conditions and one waking condition. Dreams were
      assessed upon waking naturally and also using a movement-activated (actigraph)
      alarm during the night. Overall, participants reported more quasipsychotic
      characteristics during dreams (in both conditions) than when awake. This was most
      marked for paranoia and delusional thinking, but differences were also seen for
      perceptual abnormalities, mania, and anhedonia. The quality of dream experience
      seems particularly similar to psychosis in sometimes being highly self
      referential and having a paranoid content. Subjective changes to cognition and
      affect are consistent with alterations in prefrontal cortical activity during REM
      sleep that mirror those of schizophrenia.

PMID- 22966447
TI  - Neurocognitive and social cognitive approaches for improving functional outcome
      in early psychosis: theoretical considerations and current state of evidence.
AB  - Improving functional outcome, in addition to alleviating psychotic symptoms, is
      now a major treatment objective in schizophrenia research. Given the large body
      of evidence suggesting pharmacological treatments generally have minimal effects
      on indices of functioning, research has turned to psychosocial rehabilitation
      programs. Among these, neurocognitive and social cognitive interventions are at
      the forefront of this field and are argued to target core deficits inherent to
      the schizophrenia illness. However, to date, research trials have primarily
      focused on chronic schizophrenia populations, neglecting the early psychosis
      groups who are often as severely impaired in social and occupational functioning.
      This theoretical paper will outline the rationale for investigating adjunctive
      cognitive-based interventions in the early phases of psychotic illness,
      critically examine the current approach strategies used in these interventions,
      and assess the evidence supporting certain training programs for improving
      functional outcome in early psychosis. Potential pathways for future research
      will be discussed.

PMID- 22966452
TI  - Progesterone and Cerebral Function during Emotion Processing in Men and Women
      with Schizophrenia.
AB  - Schizophrenia has been associated with disturbed levels of sex-steroid hormones,
      including estrogen and testosterone. In the present study we have examined the
      implication of a less studied hormone progesterone. Forty-three patients with
      schizophrenia (21 women) and 43 control participants (21 women) underwent
      functional MRI while viewing emotionally positive, negative, and neutral images.
      Blood samples were taken prior to the scanning session to evaluate progesterone
      levels. Simple regression analyses between levels of progesterone and brain
      activations associated with emotion processing were performed using SPM5. A
      positive correlation was found between progesterone levels and brain activations
      during processing of emotionally charged images in both healthy and schizophrenia
      men, but no significant relationship was revealed in women. These preliminary
      results indicate that progesterone is significantly associated with brain
      activations during processing of positive and negative affect in healthy and
      schizophrenia men, but not in women. Further investigation is warranted.

PMID- 22966451
TI  - Gender differences in schizophrenia and first-episode psychosis: a comprehensive
      literature review.
AB  - Recent studies have begun to look at gender differences in schizophrenia and
      first-episode psychosis in an attempt to explain the heterogeneity of the
      illness. However, a number of uncertainties remain. This paper tries to summarize
      the most important findings in gender differences in schizophrenia and first
      psychosis episodes. Several studies indicate that the incidence of schizophrenia
      is higher in men. Most of the studies found the age of onset to be earlier in men
      than in women. Findings on symptoms are less conclusive, with some authors
      suggesting that men suffer more negative symptoms while women have more affective
      symptoms. Premorbid functioning and social functioning seem to be better in
      females than males. However, cognitive functioning remains an issue, with lack of
      consensus on differences in neuropsychological profile between women and men.
      Substance abuse is more common in men than women with schizophrenia and first
      episode psychosis. In terms of the disease course, women have better remission
      and lower relapse rates. Lastly, there is no evidence of specific gender
      differences in familial risk and obstetric complications. Overall, gender
      differences have been found in a number of variables, and further study in this
      area could help provide useful information with a view to improving our care of
      these patients.

PMID- 22966453
TI  - Schizophrenia as a disorder of social communication.
AB  - Evidence is reviewed for the existence of a core system for moment-to-moment
      social communication that is based on the perception of dynamic gestures and
      other social perceptual processes in the temporal-parietal occipital junction
      (TPJ), including the posterior superior temporal sulcus (PSTS) and surrounding
      regions. Overactivation of these regions may produce the schizophrenic syndrome.
      The TPJ plays a key role in the perception and production of dynamic social,
      emotional, and attentional gestures for the self and others. These include
      dynamic gestures of the body, face, and eyes as well as audiovisual speech and
      prosody. Many negative symptoms are characterized by deficits in responding
      within these domains. Several properties of this system have been discovered
      through single neuron recording, brain stimulation, neuroimaging, and the study
      of neurological impairment. These properties map onto the schizophrenic syndrome.
      The representation of dynamic gestures is multimodal (auditory, visual, and
      tactile), matching the predominant hallucinatory categories in schizophrenia.
      Inherent in the perceptual signal of gesture representation is a computation of
      intention, agency, and anticipation or expectancy (for the self and others). The
      neurons are also tuned or biased to rapidly detect threat-related emotions. I
      review preliminary evidence that overactivation of this system can result in
      schizophrenia.

PMID- 22966454
TI  - Evaluation of factors affecting continuous performance test identical pairs
      version score of schizophrenic patients in a Japanese clinical sample.
AB  - Aim. Cognitive impairment in schizophrenia strongly relates to social outcome and
      is a good candidate for endophenotypes. When we accurately measure drug efficacy
      or effects of genes or variants relevant to schizophrenia on cognitive
      impairment, clinical factors that can affect scores on cognitive tests, such as
      age and severity of symptoms, should be considered. To elucidate the effect of
      clinical factors, we conducted multiple regression analysis using scores of the
      Continuous Performance Test Identical Pairs Version (CPT-IP), which is often used
      to measure attention/vigilance in schizophrenia. Methods. We conducted the CPT-IP
      (4-4 digit) and examined clinical information (sex, age, education years, onset
      age, duration of illness, chlorpromazine-equivalent dose, and Positive and
      Negative Symptom Scale (PANSS) scores) in 126 schizophrenia patients in Japanese
      population. Multiple regression analysis was used to evaluate the effect of
      clinical factors. Results. Age, chlorpromazine-equivalent dose, and PANSS
      negative symptom score were associated with mean d' score in patients. These
      three clinical factors explained about 28% of the variance in mean d' score.
      Conclusions. As conclusion, CPT-IP score in schizophrenia patients is influenced
      by age, chlorpromazine-equivalent dose and PANSS negative symptom score.

PMID- 22966455
TI  - Association between Urinary N-Acetyl-Beta-D-Glucosaminidase and Microalbuminuria
      in Diabetic Black Africans.
AB  - Diabetes mellitus is the commonest cause of ESRD worldwide and third most common
      cause in Nigeria. Recent reports from Nigeria indicate the prevalence of diabetic
      nephropathy as an aetiology of ESRD is increasing necessitating early diagnosis
      of diabetic nephropathy. We measured the urinary excretion of N-acetyl-beta-D
      glucosaminidase (NAG), NAG/creatinine ratio, urinary protein-creatinine ratio and
      calculated eGFR in 30 recently diagnosed nonhypertensive diabetics and 67
      controls. The age and sex distribution, systolic blood pressure, serum and
      urinary creatinine were similar for both groups. There was higher urinary
      excretion of NAG (304 versus 184 MUmol/h/L, P < 0.001) and NAG/creatinine ratio
      (21.2 versus 15.7 MUmol/h/L/mmolCr, P < 0.001) in the diabetics than controls.
      There was a strong correlation between NAG/creatinine ratio and
      albumin/creatinine ratio (r = 0.74, P < 0.001). A multivariate linear regression
      model showed a significant linear relationship between NAG/creatinine ratio and
      albumin/creatinine ratio after adjusting for the effect of blood pressure, age,
      sex, and serum creatinine. The strong association found between
      albumin/creatinine ratio and NAG/creatinine ratio perhaps indicates the need for
      further investigation of the clinical utility of NAG/creatinine ratio as a
      screening tool for early nephropathy in African diabetics.

PMID- 22966456
TI  - Placement of hemodialysis catheters with a technical, functional, and anatomical
      viewpoint.
AB  - Aims. Vascular access is of prime importance for hemodialysis patients. We aimed
      to study early complications of hemodialysis catheters placed in different
      central veins in patients with acute or chronic renal failure with or without
      ultrasound (US ) guidance. Material and Methods. Patients who were admitted to
      our unit between March 2008 and December 2010 with need for vascular access have
      been included. 908 patients were examined for their demographic parameters,
      primary renal disease, and indication for catheterization, type and location of
      the catheter, implantation technique, and acute complications. Results. The mean
      age of the patients was 60.6 +/- 16.0 years. 643 (70.8 %) of the catheters were
      temporary while 265 (29.2%) were permanent. 684 catheters were inserted to
      internal jugular veins, 213 to femoral, and 11 to subclavian veins. Arterial
      puncture occurred in 88 (9.7%) among which 13 had resultant subcutaneous
      hematoma. No patient had lung trauma and there had been no need for removal of
      the catheter or a surgical intervention for complications. US guidance in jugular
      vein and experience of operator decreased arterial puncture rate. Conclusion. US
      guided replacement of catheter to internal jugular vein would decrease
      complication rate. Referral to invasive nephrologists may decrease use of
      subclavian vein. Experience improves complication rates even under US guidance.

PMID- 22966458
TI  - Neighborhood Influences on Late Life Cognition in the ACTIVE Study.
AB  - Low neighborhood-level socioeconomic status has been associated with poorer
      health, reduced physical activity, increased psychological stress, and less
      neighborhood-based social support. These outcomes are correlates of late life
      cognition, but few studies have specifically investigated the neighborhood as a
      unique source of explanatory variance in cognitive aging. This study supplemented
      baseline cognitive data from the ACTIVE (Advanced Cognitive Training for
      Independent and Vital Elderly) study with neighborhood-level data to investigate
      (1) whether neighborhood socioeconomic position (SEP) predicts cognitive level,
      and if so, whether it differentially predicts performance in general and specific
      domains of cognition and (2) whether neighborhood SEP predicts differences in
      response to short-term cognitive intervention for memory, reasoning, or
      processing speed. Neighborhood SEP positively predicted vocabulary, but did not
      predict other general or specific measures of cognitive level, and did not
      predict individual differences in response to cognitive intervention.

PMID- 22966457
TI  - Systemic vascular function is associated with muscular power in older adults.
AB  - Age-associated loss of muscular strength and muscular power is a critical
      determinant of loss of physical function and progression to disability in older
      adults. In this study, we examined the association of systemic vascular function
      and measures of muscle strength and power in older adults. Measures of vascular
      endothelial function included brachial artery flow-mediated dilation (FMD) and
      the pulse wave amplitude reactive hyperemia index (PWA-RHI). Augmentation index
      (AIx) was taken as a measure of systemic vascular function related to arterial
      stiffness and wave reflection. Measures of muscular strength included one
      repetition maximum (1RM) for a bilateral leg press. Peak muscular power was
      measured during 5 repetitions performed as fast as possible for bilateral leg
      press at 40% 1RM. Muscular power was associated with brachial FMD (r = 0.43, P <
      0.05), PWA-RHI (r = 0.42, P < 0.05), and AIx (r = -0.54, P < 0.05). Muscular
      strength was not associated with any measure of vascular function. In conclusion,
      systemic vascular function is associated with lower-limb muscular power but not
      muscular strength in older adults. Whether loss of muscular power with aging
      contributes to systemic vascular deconditioning or vascular dysfunction
      contributes to decrements in muscular power remains to be determined.

PMID- 22966459
TI  - Falls and physical activity in persons with multiple sclerosis.
AB  - Objectives. To examine the association between fall history and physical activity
      using an objective measure of physical activity (i.e., accelerometry) in persons
      with multiple sclerosis. Design. A community-based sample of 75 ambulatory
      persons with multiple sclerosis volunteered for the investigation. Participants
      self-reported fall history in the last year, underwent a neurological exam to
      determine Expanded Disability Status Scale (EDSS) score, and wore an
      accelerometer around the waist for 7 consecutive days to determine physical
      activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in
      the last year with 28 of the 37 falling more than once. Persons who fell in the
      last year had a significantly lower number of steps/day than nonfallers (3510
      versus 4940 steps/day; P < .05). However, when controlling for disability status
      there was no statistically significant difference between fallers and nonfallers
      (4092 versus 4373 steps/day; P > .05). Conclusions. Collectively, the findings
      suggest that fall history may have little impact on current physical activity
      levels in persons with multiple sclerosis.

PMID- 22966460
TI  - Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.
AB  - Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by
      preventing cytokine transcription and lymphocyte activation. Combining the
      immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant
      tacrolimus (Prograf) may have the potential of additive therapeutic benefit
      through the complementary mechanisms of action of these two therapeutics. In this
      randomized, open-label, multicenter, two-arm pilot study, the authors examined
      the safety and tolerability of the combination of interferon beta-1b and
      tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS)
      multiple sclerosis patients who have failed one or more immunomodulatory
      therapies. Patients (n = 25) received a combination of interferon beta-1b
      subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1
      5 ng/mL, or high blood level tacrolimus, 5-10 ng/mL) for a period of 38 weeks.
      The combination therapy of interferon beta-1b and tacrolimus over the 10-month
      period of the study was shown to be safe and relatively well tolerated. There
      were no unexpected adverse events occurring as the result of the combination
      therapy. Further study of this combination therapy in patients with multiple
      sclerosis unresponsive to conventional therapy is warranted.

PMID- 22966461
TI  - The integration of cognitive remediation therapy into the whole psychosocial
      rehabilitation process: an evidence-based and person-centered approach.
AB  - Cognitive remediation therapies seem to ameliorate cognitive impairments in
      patients with schizophrenia. Interestingly, some improvement in daily functioning
      can also be expected as a result. However, to achieve these results it is
      necessary that cognitive remediation is carried out in the context of broader
      psychosocial rehabilitation involving the learning of other communication,
      social, and self-control skills. Unfortunately, little is known about how to
      integrate these different rehabilitation tools in broader rehabilitation
      programs. Based on both the neurocognitive behavioral approach and the action
      theory framework, a hierarchical flowchart is represented in this paper to
      integrate CRT with other evidence-based psychological therapies in outpatient
      settings. Finally, some evidence is provided in which cognitive abilities need to
      be targeted in remediation programs to improve functioning. In summary, to
      improve daily functioning, according to these studies, cognitive remediation
      needs to include the teaching of some cognitive strategies that target executive
      skills.

PMID- 22966462
TI  - Enhancing work-focused supports for people with severe mental illnesses in
      australia.
AB  - Persons with severe mental illness (SMI) have reduced workforce participation,
      which leads to significant economic and social disadvantage. This theoretical
      review introduces the strategies that have been implemented to address this
      issue. These include Individual Placement and Support (IPS) services, the most
      widely researched form of supported employment, to which cognitive remediation
      has more recently been recognised in the USA, as an intervention to improve
      employment outcomes by addressing the cognitive impairments often experienced by
      people with SMI. The authors review the international literature and discuss
      specifically the Australian context. They suggest that Australia is in a prime
      position to engage clients in such a dual intervention, having had recent success
      with increasing access to supported employment programs and workforce reentry,
      through implementation of the Health Optimisation Program for Employment (HOPE).
      Such programs assist with gaining and maintaining employment. However, they do
      not address the cognitive issues that often prevent persons with SMI from
      effectively participating in work. Thus, optimising current interventions, with
      work-focused cognitive skills development is critical to enhancing employment
      rates that remain low for persons with SMI.

PMID- 22966463
TI  - Hypofractionated Prostate Radiotherapy with or without Conventionally
      Fractionated Nodal Irradiation: Clinical Toxicity Observations and Retrospective
      Daily Dosimetry.
AB  - Purpose. To evaluate toxicity associated with the addition of elective nodal
      irradiation (ENI) to a hypofractionated regimen for the treatment of prostate
      cancer. Methods and Materials. Fifty-seven patients received pelvic image-guided
      IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the
      prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy
      in 28 fractions. Results. Median followup was 41.1 months. Early grade >=2
      urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18
      of 31) for those not (P = 0.61). Early grade >=2 rectal toxicity rates were 40%
      (23 of 57) and 23% (7 of 31), respectively (P = 0.09). The addition of ENI
      resulted in a 21% actuarial rate of late grade >=2 rectal toxicity at 4 years,
      compared to 0% for patients treated to the prostate only (P = 0.02).
      Retrospective daily dosimetry of patients experiencing late rectal toxicity
      revealed an average increase of 2.67% of the rectal volume receiving 70 Gy
      compared to the original plan. Conclusions. The addition of ENI resulted in an
      increased risk of late rectal toxicity. Grade >=2 late rectal toxicity was
      associated with worse daily rectal dosimetry compared to the treatment plan.

PMID- 22966465
TI  - Degenerative cervical spondylosis: natural history, pathogenesis, and current
      management strategies.

PMID- 22966464
TI  - Fungal infections: their diagnosis and treatment in transplant recipients.
AB  - Systemic fungal infections typically occur in individuals who are seriously ill
      with recognized risk factors such as those frequently found in transplant
      recipients. Unfortunately, they are often diagnosed late, when the efficacy of
      the available treatments is low, often less than 50%, and the cost in terms of
      lives lost, hospital length of stay, and total hospital costs is substantially
      increased. The application of antifungal therapies associated with reported
      efficacy rates greater than 50% are those used prophylactically. When used
      prophylactically, these infections are reduced in greater than 95% of the
      expected cases. The choice of a prophylactic agent should be based upon its ease
      of administration, lack of adverse effects, reduced likelihood of potential drug
      interactions, and its efficacy in patients with established risk factors and
      comorbid disease processes that include renal, hepatic, and chronic pulmonary
      disease. The indications for the use of currently available antifungal agents,
      their adverse effects, drug interactions, ease of dosing, and applicability in
      patients with preexisting disease states, and especially in liver transplant
      recipients, are presented in this paper.

PMID- 22966466
TI  - Transcatheter arterial chemoembolization: history for more than 30 years.
AB  - Transcatheter arterial chemoembolization (TACE) is a minimally invasive technique
      to treat liver tumors, particularly hepatocellular carcinoma (HCC). TACE was used
      in early times to treat liver tumor patients with emergencies caused by
      symptomatic humoral hypercalcemia and develops gradually from the procedures of
      diagnostic angiography and transcatheter injection of agents and is in particular
      performed in the treatment of HCC. Since the beginning of this century, TACE has
      been used extensively in the palliative treatment of unresectable HCC. In recent
      years, it is indicated in selected patients with early-stage HCC. This review
      introduces the evolution of TACE for more than 30 years, its role in
      comprehensive treatment of HCC, the tendency of its refinement in future, and the
      combination use of TACE with other local ablative methods for the curative result
      of HCC.

PMID- 22966467
TI  - Pharmacological Evaluation and Docking Studies of 3-Thiadiazolyl- and Thioxo
      1,2,4-triazolylcoumarin Derivatives as Cholinesterase Inhibitors.
AB  - Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is
      considered a promising strategy for the treatment of Alzheimer's disease (AD).
      This research project aims to provide a comprehensive knowledge of newly
      synthesized coumarin analogues with anti-AD potential. In the present work a
      series of 3-thiadiazolyl- and thioxo-1,2,4-triazolylcoumarins derivatives were
      designed, synthesized, and tested as potent inhibitors of cholinesterases. These
      compounds were assayed against AChE from electrophorus electricus and rabbit; and
      BChE from horse serum and rabbit by Ellman's method using neostigmine
      methylsulphate and donepezil as reference drugs. Some of the assayed compounds
      proved to be potent inhibitors of AChE and BChE with K(i) values in the
      micromolar range. 4b was found to be the most active compound with K(i) value
      0.028 +/- 0.002 MUM and higher selectivity for AChE/BChE. The ability of 4b to
      interact with AChE was further confirmed through computational studies, in which
      a primary binding was proved to occur at the active gorge site, and a secondary
      binding was revealed at the peripheral anionic site. Structure activity
      relationships of prepared compounds were also discussed.

PMID- 22966468
TI  - Spontaneous primary intraventricular hemorrhage: clinical features and early
      outcome.
AB  - Purpose. Primary hemorrhage in the ventricular system without a recognizable
      parenchymal component is very rare. This single-center retrospective study aimed
      to further characterize the clinical characteristics and early outcome of this
      stroke subtype. Methods. All patients with primary intraventricular hemorrhage
      included in a prospective hospital-based stroke registry over a 19-year period
      were assessed. A standardized protocol with 161 items, including demographics,
      risk factors, clinical data, neuroimaging findings, and outcome, was used for
      data collection. A comparison was made between the groups of primary
      intraventricular hemorrhage and subcortical intracerebral hemorrhage. Predictors
      of primary intraventricular hemorrhage were identified by logistic regression
      analysis. Results. There were 12 patients with primary intraventricular
      hemorrhage (0.31% of all cases of stroke included in the database) and 133 in the
      cohort of subcortical hemorrhage. Very old age (>=85 years) (odds ratio (OR)
      9.89), atrial fibrillation (OR 8.92), headache (OR 6.89), and altered
      consciousness (OR 4.36) were independent predictors of intraventricular
      hemorrhage. The overall in-hospital mortality rate was 41.7% (5/12) but increased
      to 60% (3/5) in patients aged 85 years or older. Conclusion. Although primary
      intraventricular hemorrhage is uncommon, it is a severe clinical condition with a
      high early mortality. The prognosis is particularly poor in very old patients.

PMID- 22966469
TI  - Duodenal tumor presenting as acquired hemophilia in an 88-year-old woman: a
      clinical case and review of the literature.
AB  - Acquired hemophilia is a rare disease, presenting with severe hemorrhage, we
      present a case caused by a duodenal tumor, the clinical management, ethical
      implications, treatment recommendations, and a review of the literature.

PMID- 22966470
TI  - Two case reports of neuroinvasive west nile virus infection in the critical care
      unit.
AB  - We describe the clinical course of two cases of neuroinvasive West Nile Virus
      (WNV) infection in the critical care unit. The first case is a 70-year-old man
      who presented during summer with mental status changes. Cerebrospinal fluid (CSF)
      analysis revealed pleocytosis with lymphocyte predominance. WNV serology was
      positive in the CSF. His condition worsened with development of left-sided
      weakness and deterioration of mental status requiring intensive care. The patient
      gradually improved and was discharged with residual left-sided weakness and near
      complete improvement in his mental status. The second case is an 81-year-old man
      who presented with mental status changes, fever, lower extremity weakness, and
      difficulty in walking. CSF analysis showed pleocytosis with neutrophil
      predominance. WNV serology was also positive in CSF. During the hospital stay his
      mentation worsened, eventually requiring intubation for airway protection and
      critical care support. The patient gradually improved and was discharged with
      residual upper and lower extremity paresis. Neuroinvasive WNV infection can lead
      to significant morbidity, especially in the elderly. These cases should be
      suspected in patients with antecedent outdoor activities during summer. It is
      important for critical care providers to be aware of and maintain a high clinical
      suspicion of this disease process.

PMID- 22966471
TI  - A challenging case of metastatic intra-abdominal synovial sarcoma with unusual
      immunophenotype and its differential diagnosis.
AB  - The primary and metastatic gastrointestinal synovial sarcoma is rare with a wide
      differential diagnosis. It usually expresses cytokeratins EMA, BCL2 with an
      occasional CD99, and S100 positivity but not desmin. We present a case of
      metastatic synovial sarcoma with unusual immunophenotype causing diagnostic
      challenges. The tumor cells showed focal cytokeratin, EMA, and, unexpectedly,
      desmin positivity. Additional intranuclear TLE-1 positivity and negativity for
      CD34 and DOG-1 were also identified. A diagnosis of monophasic synovial sarcoma
      was confirmed by using FISH break-apart probe. RT-PCR revealed the SYT-SSX1
      fusion gene. Intra-abdominal synovial sarcoma, either primary or metastatic, with
      unusual desmin positivity raises the diagnostic challenge, since a wide range of
      differential diagnoses could show a similar immunophenotype (leiomyosarcoma,
      desmoid tumor, myofibroblastic tumor, and rarely GIST etc.). Typical morphology
      and focal cytokeratin/EMA positivity should alert to this tumor, and FISH and RT
      PCR remain the gold standard for the confirmation.

PMID- 22966472
TI  - ECMO for Cardiac Rescue after Accidental Intravenous Mepivacaine Application.
AB  - Mepivacaine is a potent local anaesthetic and used for infiltration and regional
      anaesthesia in adults and pediatric patients. Intoxications with mepivacaine
      affect mainly the CNS and the cardiovascular system. We present a case of
      accidental intravenous mepivacaine application and intoxication of an infant
      resulting in seizure, broad complex bradyarrhythmia, arterial hypotension and
      finally cardiac arrest. The patient could be rescued by prolonged resuscitations
      and a rapid initiation of ECMO and survived without neurological damage. The
      management strategies of this rare complication including promising other
      treatment options with lipid emulsions are discussed.

PMID- 22966473
TI  - Endolymphatic sac enlargement in a girl with a novel mutation for distal renal
      tubular acidosis and severe deafness.
AB  - Hereditary distal renal tubular acidosis (dRTA) is caused by mutations of genes
      encoding subunits of the H(+)-ATPase (ATP6V0A4 and ATP6V1B1) expressed in alpha
      intercalated cells of the distal renal tubule and in the cochlea. We report on a
      2-year-old girl with distal RTA and profound speech delay which was initially
      misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations
      with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic
      resonance imaging (MRI) revealed bilateral enlargement of the endolymphatic sacs
      of the inner ear. With improved cooperation, audiometric testing showed that
      hearing loss was most profound on the right, where endolymphatic sac enlargement
      was greatest, demonstrating a clear link between the degree of deafness and the
      degree of inner ear abnormality. This case indicates the value of MRI for
      diagnosis of inner ear involvement in very young children with distal RTA.
      Although citrate therapy quickly corrects the acidosis and restores growth, early
      diagnosis of deafness is crucial so that hearing aids can be used to assist
      acquisition of speech and to provide enough auditory nerve stimulation to assure
      the affected infants remain candidates for cochlear implantation.

PMID- 22966474
TI  - Infantile myofibroma eroding into the frontal bone: a case report and review of
      its histopathologic differential diagnosis.
AB  - Infantile myofibroma is a rare and benign tumour of children presenting in the
      head and neck region. Rendering a final diagnosis of infantile myofibroma can be
      challenging in the light of nonspecific clinical, radiological findings and its
      histopathological similarities with a number of neoplasms especially spindle cell
      tumours. In this paper we discuss a case of infantile myofibroma in a 2-month-old
      infant, enumerating the various differential entities that have to be eliminated
      in reaching its specific diagnosis and highlighting the importance of
      immunopositivity to vimentin and smooth muscle actin (SMA) in establishing its
      myofibroblastic differentiation.

PMID- 22966475
TI  - Case report: delayed perforation after definitive treatment of focal intestinal
      perforation with a peritoneal drain.
AB  - Focal intestinal perforation (FIP) has long been described in the pediatric
      literature. Peritoneal drainage (PD) is widely used as treatment for focal
      intestinal perforation. Here we report a premature infant that underwent PD on
      day of life 9 for a FIP. The infant recovered well from this episode and was
      discharged home without known sequelae. Subsequently, the same patient presented
      16 months later with peritonitis. A perforation was discovered at laparotomy
      without evidence of surrounding necrosis. Given this finding, we believe this
      second episode of perforation was at the same site as the initial episode of FIP.
      The finding of FIP has been described without findings of surrounding necrosis.
      However, we believe this to be the first report of delayed perforation greater
      than 1 year from initial presentation after FIP treated definitively with
      peritoneal drain.

PMID- 22966477
TI  - Mitochondrial dynamics and mitophagy in the 6-hydroxydopamine preclinical model
      of Parkinson's disease.
AB  - We discuss the participation of mitochondrial dynamics and autophagy in the 6
      hydroxidopamine-induced Parkinson's disease model. The regulation of dynamic
      mitochondrial processes such as fusion, fission, and mitophagy has been shown to
      be an important mechanism controlling cellular fate. An imbalance in
      mitochondrial dynamics may contribute to both familial and sporadic
      neurodegenerative diseases including Parkinson's disease. With special attention
      we address the role of second messengers as the role of reactive oxygen species
      and the mitochondria as the headquarters of cell death. The role of molecular
      signaling pathways, for instance, the participation of Dynamin-related protein
      1(Drp1), will also be addressed. Furthermore evidence demonstrates the
      therapeutic potential of small-molecule inhibitors of mitochondrial division in
      Parkinson's disease. For instance, pharmacological inhibition of Drp1, through
      treatment with the mitochondrial division inhibitor-1, results in the abrogation
      of mitochondrial fission and in a decrease of the number of autophagic cells.
      Deciphering the signaling cascades that underlie mitophagy triggered by 6-OHDA,
      as well as the mechanisms that determine the selectivity of this response, will
      help to better understand this process and may have impact on human treatment
      strategies of Parkinson's disease.

PMID- 22966478
TI  - Dopamine oxidation and autophagy.
AB  - The molecular mechanisms involved in the neurodegenerative process of Parkinson's
      disease remain unclear. Currently, there is a general agreement that
      mitochondrial dysfunction, alpha-synuclein aggregation, oxidative stress,
      neuroinflammation, and impaired protein degradation are involved in the
      neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's
      disease. Aminochrome has been proposed to play an essential role in the
      degeneration of dopaminergic neurons containing neuromelanin by inducing
      mitochondrial dysfunction, oxidative stress, the formation of neurotoxic alpha
      synuclein protofibrils, and impaired protein degradation. Here, we discuss the
      relationship between the oxidation of dopamine to aminochrome, the precursor of
      neuromelanin, autophagy dysfunction in dopaminergic neurons containing
      neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy
      dysfunction in dopaminergic neurons. Aminochrome induces the following: (i) the
      formation of alpha-synuclein protofibrils that inactivate chaperone-mediated
      autophagy; (ii) the formation of adducts with alpha- and beta-tubulin, which
      induce the aggregation of the microtubules required for the fusion of autophagy
      vacuoles and lysosomes.

PMID- 22966479
TI  - Herd-level risk factors for bovine tuberculosis: a literature review.
AB  - Bovine tuberculosis (TB), caused by Mycobacterium bovis, is one of the most
      challenging endemic diseases currently facing government, the veterinary
      profession, and the farming industry in the United Kingdom and Ireland and in
      several other countries. The disease has a notoriously complex epidemiology; the
      scientific evidence supports both cattle-cattle and wildlife-cattle transmission
      routes. To produce more effective ways of reducing such transmission, it is
      important to understand those risk factors which influence the presence or
      absence of bovine TB in cattle herds. Here we review the literature on herd-level
      risk factor studies. Whilst risk factors operate at different scales and may vary
      across regions, epidemiological studies have identified a number of risk factors
      associated with bovine TB herd breakdowns, including the purchase of cattle, the
      occurrence of bovine TB in contiguous herds, and/or the surrounding area as well
      as herd size. Other factors identified in some studies include farm and herd
      management practices, such as, the spreading of slurry, the use of certain
      housing types, farms having multiple premises, and the use of silage clamps. In
      general, the most consistently identified risk factors are biologically plausible
      and consistent with known transmission routes involving cattle-cattle and
      wildlife-cattle pathways.

PMID- 22966480
TI  - Lactose malabsorption and intolerance: What should be the best clinical
      management?
AB  - Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase
      deficiency, which may occur as a primary disorder or secondary to other
      intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive
      condition resulting from the physiological decline of lactase activity. Different
      methods have been used to diagnose LM. Lactose breath test represents the most
      reliable technique. A recent consensus conference has proposed the more
      physiological dosage of 25 g of lactose and a standardized procedure for breath
      testing. Recently a new genetic test, based on C/T13910 polymorphism, has been
      proposed for the diagnosis of adult-type hypolactasia, complementing the role of
      breath testing. LM represents a well-known cause of abdominal symptoms although
      only some lactose malabsorbers are also intolerants. Diagnosing lactose
      intolerance is not straightforward. Many non-malabsorber subjects diagnose
      themselves as being lactose intolerant. Blind lactose challenge studies should be
      recommended to obtain objective results. Besides several studies indicate that
      subjects with lactose intolerance can ingest up to 15 g of lactose with no or
      minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted
      diet avoiding the nutritional disadvantages of reduced calcium and vitamin
      intake.Various pharmacological options are also available. Unfortunately there is
      insufficient evidence that these therapies are effective. Further double-blind
      studies are needed to demonstrate treatment effectiveness in lactose intolerance.

PMID- 22966481
TI  - Prolonged fever after Infliximab infusion.
AB  - Pharmacologic management for ulcerative colitis (UC) has recently been expanded
      to include anti- tumor necrosis factor (TNF) therapy for severe disease.
      Infliximab, a chimeric monoclonal antibody directed again TNF alpha was first
      tested in patients with Crohn's disease. In addition to serious infections,
      malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like
      reactions, neurological disease, and infusion reactions further complicate the
      use of Infliximab. We report a case of prolonged fever after Infliximab infusion
      to treat steroid refractory UC.

PMID- 22966482
TI  - Prevention of hepatitis C recurrence after liver transplantation: An update.
AB  - Hepatitis C related liver failure and hepatocarcinoma are the most common
      indications for liver transplantation in Western countries. Recurrent hepatitis C
      infection of the allograft is universal and immediate following liver
      transplantation, being associated with accelerated progression to cirrhosis,
      graft loss and death. Graft and patient survival is reduced in liver transplant
      recipients with recurrent Hepatitis C virus (HCV) infection compared to HCV
      negative recipients. Many variables may impact on recurrent HCV liver disease.
      Overall, excess immunosuppression is believed to be a key factor; however, no
      immunosuppressive regimen has been identified to be more beneficial or less
      harmful. Donor age limitations, exclusion of moderately to severely steatotic
      livers and minimization of ischemic times could be a potential strategy to
      minimize the severity of HCV disease in transplanted subjects. After
      transplantation, antiviral therapy based on pegylated IFN alpha with or without
      ribavirin is associated with far less results than that reported for
      immunocompetent HCV-infected patients. New findings in the field of immunotherapy
      and genomic medicine applied to this context are promising.

PMID- 22966484
TI  - Rifaximin therapy and hepatic encephalopathy: Pros and cons.
AB  - Hepatic encephalopathy (HE) is the second most common major complication in
      cirrhotics and it significantly impacts quality of life. Therapeutic approaches
      for HE treatment and prevention mainly continue to rely on ammonia-lowering
      strategies and non-absorbable disaccharides are currently considered the
      cornerstone therapy. Non-absorbable antibiotics, such as neomycin and
      paramomycin, are effective in treatment of acute HE episodes but their prolonged
      use for recurrence prevention is hampered by possible side-effects. To overcome
      these limitations, rifaximin use has been proposed. Rifaximin has been shown to
      be not superior to non-absorbable disaccharides for either HE treatment or
      prevention, with a similar incidence of side-effects. Cirrhosis significantly
      increases rifaximin absorption and this could be a cause for concern. Following
      long-term rifaximin therapy, Clostridium difficile colitis has been observed and
      Candida albicans has been isolated from 20% of patients. In addition, selection
      of resistant mutants of both Gram-negative and -positive bacteria in the
      gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations
      (sodium and potassium) have been reported during rifaximin therapy, a warning for
      its long-term use in cirrhotics. Moreover, a potential interference with vitamin
      K production should be considered which could further impair the already altered
      clotting status of these patients. The therapeutic cost of rifaximin is markedly
      higher than non-absorbable disaccharides. While waiting for further safety data,
      caution should be used to limit the use of rifaximin therapy for a very short
      term period in selected HE cirrhotics not responding to non-absorbable
      disaccharides.

PMID- 22966485
TI  - Helicobacter pylori therapy: Present and future.
AB  - Helicobacter pylori (H. pylori) plays a crucial role in the pathogenesis of
      chronic active gastritis, peptic ulcer and gastric mucosa-associated lymphoid
      tissue-lymphoma, and is also involved in carcinogenesis of the stomach. H. pylori
      treatment still remains a challenge for physicians, since no current first-line
      therapy is able to cure the infection in all treated patients. Several factors
      may help in the eradication of therapy failure. We reviewed both bacterial and
      host factors involved in therapeutic management of the H. pylori infection. In
      addition, we evaluated data on the most successful therapy regimens - sequential
      and concomitant therapies - currently available for H. pylori eradication.

PMID- 22966486
TI  - Introducing cymantrene labels into scattering scanning near-field infrared
      microscopy.
AB  - In this paper we investigate metal-organic compounds as infrared (IR) active
      labels by scattering scanning near-field infrared microscopy (IR s-SNOM, often
      also abbreviated as s-SNIM) with a lateral resolution of 90 * 90 nm(2). Tailor
      made IR spectroscopic probes based on cymantrene (CpMn(CO)(3) with Cp = eta(5)
      C(5)H(5)) conjugated to a cysteine-modified pseudoneurotensin (pNT-Cys-OH)
      peptide were prepared by automated microwave-assisted solid phase peptide
      synthesis (SPPS) and characterized by HPLC, ESI-MS and IR. Well-defined patterned
      self-assembled monolayers on a gold surface were prepared by microcontact
      printing of 1-octadecanethiol (ODT) followed by additional incubation in
      ethanolic solution of the cymantrene-peptide derivative. The self-assembled
      monolayers have been evidenced by infrared reflection absorption spectroscopy
      (IRRAS) and AFM. CO laser source radiation was tuned (1944, 1900, 1798 and 1658
      cm(-1)) for imaging contrast with good matching correlation between spectroscopic
      and topographic patterns at specific characteristic metal carbonyl and amide
      bands (1944 cm(-1) (lambda = 5.14 MUm) and 1658 cm(-1) (lambda = 6.03 MUm)).
      Cymantrene probes provide an attractive method to tag a unique spectroscopic
      feature on any bio(macro)molecule. Introducing such probes into super-resolution
      IR s-SNOM will enable molecular tracking and distribution studies even in complex
      biological systems.

PMID- 22966483
TI  - Liver transplantation in adults: Choosing the appropriate timing.
AB  - Liver transplantation is indicated in patients with acute liver failure,
      decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic
      defects that trigger damage of other organs. Early referral to a transplant
      center is crucial in acute liver failure due to the high mortality with medical
      therapy and its unpredictable evolution. Referral to a transplant center should
      be considered when at least one complication of cirrhosis occurs during its
      natural history. However, because of the shortage of organ donors and the short
      term mortality after liver transplantation on one hand and the possibility of
      managing the complications of cirrhosis with other treatments on the other,
      patients are carefully selected by the transplant center to ensure that
      transplantation is indicated and that there are no medical, surgical and
      psychological contraindications. Patients approved for transplantation are placed
      on the transplant waiting list and prioritized according to disease severity.
      Thus, the appropriate timing of transplantation depends on recipient disease
      severity and, although this is still a matter of debate, also on donor quality.
      These two variables are known to determine the "transplant benefit" (i.e., when
      the expected patient survival is better with, than without, transplantation) and
      should guide donor allocation.

PMID- 22966487
TI  - Signal amplification based on DNA hybridization-dehybridization reaction on the
      surface of magnet submicrobeads for ultrasensitive DNA detection.
AB  - A new signal amplification strategy based on DNA hybridization-dehybridization
      reaction on the surface of magnetic submicrobeads (MSBs) for fluorescence
      detection of ultrasensitive DNA was developed. In this strategy, MSBs modified
      with probe DNA (DNAp-MSBs) were bound to target DNA (t-DNA) (with a ratio of 1 :
      1) captured to a substrate. The DNAp-MSBs were released from the substrate via
      DNA dehybridization and then hybridized with Cy5-labeled detection DNA (Cy5
      DNAd). After the Cy5-DNAd and DNAp-MSBs were separated by dehybridization, the
      Cy5-DNAd was collected. The DNAp-MSBs were then hybridized with other Cy5-DNAd to
      initiate the next hybridization-dehybridization round. This recycling of the
      hybridization-dehybridization process on the surface of the DNAp-MSBs was
      repeated multiple times to accumulate Cy5-DNAd. Finally, fluorescence intensity
      of the collected Cy5-DNAd was measured. Using this strategy, the limit of
      detection for determination of t-DNA was 8.5 * 10(-15) mol L(-1) for 11 cycles.
      The ultrasensitive assay was used to quantify ribosomal protein, large, P2
      (RPLP2) mRNA in human breast cancer cells.

PMID- 22966488
TI  - From individual cognition to populational culture.
AB  - In my response to the commentaries from a collection of esteemed researchers, I
      reassess and eventually find largely intact my claim that human tool use
      evidences higher social and non-social cognitive ability. Nonetheless, I concede
      that my examination of individual-level cognitive traits does not offer a full
      explanation of cumulative culture yet. For that, one needs to incorporate them
      into population-dynamic models of cultural evolution. I briefly describe my
      current and future work on this.

PMID- 22966489
TI  - In brief: Taliglucerase (Elelyso) for Gaucher disease.

PMID- 22966492
TI  - Free drugs for India's poor.

PMID- 22966491
TI  - Vermont attempts single-payer health care.

PMID- 22966493
TI  - Can Canada reckon with its health costs?

PMID- 22966494
TI  - It's about time.

PMID- 22966497
TI  - Revisiting ethics.

PMID- 22966495
TI  - Plant root research: the past, the present and the future.
AB  - This special issue is dedicated to root biologists past and present who have been
      exploring all aspects of root structure and function with an extensive
      publication record going over 100 years. The content of the Special Issue on Root
      Biology covers a wide scale of contributions, spanning interactions of roots with
      microorganisms in the rhizosphere, the anatomy of root cells and tissues, the
      subcellular components of root cells, and aspects of metal accumulation and
      stresses on root function and structure. We have organized the papers into three
      topic categories: (1) root ecology, interactions with microbes, root architecture
      and the rhizosphere; (2) experimental root biology, root structure and
      physiology; and (3) applications of new technology to study root biology.
      Finally, we will speculate on root research for the future.

PMID- 22966498
TI  - Revisiting ethics.

PMID- 22966499
TI  - Is the golden age over?

PMID- 22966500
TI  - Magnesium and the inflammatory response: potential pathophysiological
      implications in the management of patients with aneurysmal subarachnoid
      hemorrhage?
AB  - Cerebral vasospasm and delayed cerebral ischemia remain an unsolved problem in
      patients with aneurysmal subarachnoid hemorrhage (SAH). In theory, high-dose
      magnesium sulfate (MgSO(4)) therapy offers vascular and neuroprotective benefits
      and is therefore currently under evaluation. The intensity of the inflammatory
      response after SAH is associated with the outcome. The aim of the current study
      was to evaluate a possible link between the inflammatory response and MgSO(4)
      therapy, since magnesium (Mg(2+)) has anti-inflammatory properties. In 15
      patients with SAH, inflammatory cytokine levels in the cerebrospinal fluid (CSF)
      and peripheral blood were determined daily using an enzyme-linked immunosorbent
      assay between day 4 and day 12. Eight patients were treated with standard therapy
      alone (group 1) and seven patients were treated with an additional, high-dose of
      MgSO(4) (group 2). Serum Mg(2+) levels in group 2 were significantly higher
      compared to group 1: 1.48 +/- 0.04 mmol/L versus 0.90 +/- 0.01 mmol/L, rho<0.001.
      Interleukin-6 (IL-6) in the CSF was significantly lower in group 2 compared to
      group 1: 6680 +/- 989 vs.11079 +/- 1277 pg/mL, rho = 0.021. A trend towards lower
      systemic IL-6 levels was found in group 2: 58 +/- 7 versus 104 +/- 21 pg/mL, rho
      = 0.052. Systemic IL-1beta levels were significantly lower in group 2: 0.66 +/-
      0.11 and 0.15 +/- 0.01 pg/mL (rho<0.001), while the CSF levels did not differ.
      Tumor necrosis factor-alpha levels did not differ between the two groups.
      Although there were more patients with favorable outcome in group 2, the
      difference was not statistically significant. This was probably due to the small
      sample size. The results indicate a suppression of inflammatory cytokine release,
      in particular IL-6, in patients treated with high-dose MgSO(4). These results
      call for further studies of the effect of Mg(2+) on the inflammatory signaling
      pathway with regard to delayed cerebral ischemia following SAH.

PMID- 22966501
TI  - Medical Area Body Network. Final rule.
AB  - This document expands the Commission's Medical Device Radiocommunications Service
      (MedRadio) rules to permit the development of new Medical Body Area Network
      (MBAN) devices in the 2360-2400 MHz band. The MBAN technology will provide a
      flexible platform for the wireless networking of multiple body transmitters used
      for the purpose of measuring and recording physiological parameters and other
      patient information or for performing diagnostic or therapeutic functions,
      primarily in health care facilities. This platform will enhance patient safety,
      care and comfort by reducing the need to physically connect sensors to essential
      monitoring equipment by cables and wires. This decision is the latest in a series
      of actions to expand the spectrum available for wireless medical use. The
      Commission finds that the risk of increased interference is minimal and is
      greatly outweighed by the benefits of the MBAN rules.

PMID- 22966502
TI  - Recent developments in health law. Isolated DNA patents: incentivizing medical
      research or selling humanidentity?

PMID- 22966503
TI  - Recent developments in health law. Puerto Rico creates legal precedent for
      regulation of aesthetic medicine.

PMID- 22966504
TI  - Recent developments in health law. Compensating victims of forced sterilization.

PMID- 22966505
TI  - Reviving the pinto? Let's hope not.

PMID- 22966506
TI  - ACA 101. Beyond insurance: do you know what else is in the law?

PMID- 22966507
TI  - John Q. Public: an ACO? What's that?

PMID- 22966508
TI  - Level playing field. Ferreting out variation leads to greater efficiencies,
      patient care.

PMID- 22966509
TI  - Bedside delivery. An easier pill to swallow.

PMID- 22966510
TI  - Innovations in patient care delivery.
AB  - Hospitals are striving to become high-value organizations that provide patient
      centered, fiscally prudent care. This foldout includes a CEO checklist, five
      steps to innovation and case studies of two health care systems.

PMID- 22966511
TI  - Your tracking number is ...

PMID- 22966512
TI  - Stars of the field. The AHA awards issue. The rewards of awards.
AB  - These outstanding organizations lead ambitious efforts to improve the well-being
      of their communities, providing important lessons for hospitals everywhere. We
      applaud them.

PMID- 22966514
TI  - AHA NOVA award.

PMID- 22966513
TI  - Quest for Quality award.

PMID- 22966515
TI  - Circle of Life award.

PMID- 22966516
TI  - Giant steps forward in palliative care: Calvary Hospital.

PMID- 22966517
TI  - Dick Davidson award.

PMID- 22966518
TI  - Most Wired Innovator award.

PMID- 22966519
TI  - Lifelong learning: improving patient care and nursing practice.

PMID- 22966520
TI  - Magic mirror neurons: using brain science to create positive work environments.

PMID- 22966521
TI  - Strategies to help initiate and maintain the end-of-life discussion with patients
      and family members.
AB  - Nurses face barriers in the acute care setting regarding the initiation and
      maintenance of end-of-life discussions. Identification of and strategies to
      overcome these barriers are discussed.

PMID- 22966522
TI  - Early recognition and treatment of sepsis in the medical-surgical setting.
AB  - Early recognition and treatment of sepsis reduces mortality (Dellinger et al.,
      2008). Nurses are a critical part of the health care team that provides evidence
      based care to prevent, identify, and promptly treat sepsis in the hospital
      setting.

PMID- 22966523
TI  - Horizontal violence in nursing.
AB  - Horizontal or lateral violence is considered an act of aggression among nursing
      professionals. Horizontal violence creates a negative work environment impairing
      teamwork and compromising patient care. The effects of horizontal violence and
      strategies for prevention and management are addressed.

PMID- 22966524
TI  - Fast track program to prevent postoperative ileus.
AB  - A fast track program was implemented using best practices to prevent
      postoperative ileus. Patients receiving traditional care for bowel surgery were
      compared to patients on the fast track program. The incidence of ileus decreased
      43%, and length of stay decreased 1.352 days.

PMID- 22966525
TI  - Weight management practices among heart and vascular health care providers in an
      ambulatory setting.
AB  - In this study, health care providers' assessment, intervention practices, and
      perceived barriers to weight management approaches in an ambulatory adult heart
      and vascular setting are reported. Their knowledge of the National Institutes of
      Health National Heart, Lung and Blood Institute's The Practical Guide:
      Identification, Evaluation, and Treatment of Overweight and Obesity in Adults are
      also described.

PMID- 22966526
TI  - Involving patient and family advisors in the patient and family-centered care
      model.
AB  - Health care facilities that utilize patient and family advisors are experiencing
      improved outcomes in decreased length of stay, and improved reimbursements and
      patient satisfaction. Patient and family advisors can be strong allies in ongoing
      performance improvement efforts. Perhaps even more importantly, involving
      advisors in health care systems encourages treatment of the whole patient as he
      or she would want to be treated

PMID- 22966527
TI  - The merry-go-round of patient rounding: assure your patients get the brass ring.
AB  - Staff members on a medical-surgical unit in a large community teaching hospital
      adapted the hourly rounding concept to their specific patient population. Lessons
      learned and strategies to assure continuous success with the rounding process are
      addressed.

PMID- 22966528
TI  - Blood pleurodesis: thoracotomy patients and air leaks.

PMID- 22966529
TI  - Ethical challenges in the era of health care reform.

PMID- 22966530
TI  - If Tabatha took over your unit.

PMID- 22966531
TI  - Reporting quality improvement.

PMID- 22966532
TI  - Comparative analysis of electrical detection methods of DNA synthesis.
AB  - The incorporation of a complementary deoxynucleotide (dNTP) into a self-primed
      single-stranded DNA (ssDNA) attached to the surface of a sensor electrode
      generates an H+ charge that can be either trapped on the sensor surface or
      diffused into the surrounding solution. Electrical detection methods of DNA
      synthesis are based on these H+ kinetic mechanisms. The detection method that
      uses ISFET, which is related to the surface trapping mechanism, showed a better
      sensing signal than the induced charge detection method, which is related to the
      diffusion of H+ into the surrounding solution. The trapping reaction should be
      well-controlled, however, so that it would be stable under various surface
      conditions and temperatures. Moreover, the reaction should be reversible, and the
      reaction parameters should be well-sustained in the subsequent synthesis cycles.
      For the induced charge method, the AC current level was too small to be detected
      using an ordinary amplifier circuit with the same sensor size as that of ISFET.
      Consequently, the sensor operation sustainability and signal-to-noise ratio
      characteristics should be addressed carefully in the selection of the proper
      sensor type.

PMID- 22966533
TI  - Gold-coated iron oxide nanoparticles as a T2 contrast agent in magnetic resonance
      imaging.
AB  - Gold-coated iron oxide (Fe3O4) nanoparticles were synthesized for use as a T2
      contrast agent in magnetic resonance imaging (MRI). The coated nanoparticles were
      spherical in shape with an average diameter of 20 nm. The gold shell was about 2
      nm thick. The bonding status of the gold on the nanoparticle surfaces was checked
      using a Fourier transform infrared spectrometer (FTIR). The FTIR spectra
      confirmed the attachment of homocysteine, in the form of thiolates, to the Au
      shell of the Au-Fe3O4 nanoparticles. The relaxivity ratio, R2/R1, for the coated
      nanoparticles was 3-fold higher than that of a commercial contrast agent,
      Resovist, which showed the potential for their use as a T2 contrast agent with
      high efficacy. In animal experiments, the presence of the nanoparticles in rat
      liver resulted in a 71% decrease in signal intensity in T2-weighted MR images,
      indicating that our gold-coated iron oxide nanoparticles are suitable for use as
      a T2 contrast agent in MRI.

PMID- 22966534
TI  - Rapid detection of food pathogens using RNA aptamers-immobilized slide.
AB  - The purpose of this study was to develop a simple and rapid detection system for
      foodborne bacteria, which consisted of an optical microscope and its slide chip
      with artificial antibodies, or RNA aptamers. From an RNA pool, three each RNA
      aptamers were built by the method of SELEX (systematic evolution of ligands by
      exponential enrichment) for components of cell wall, LPS (lipopolysaccharide)
      from E. coli O157:H7, teichoic acid from Staphylococcus aureus and a cell
      membrane protein of OmpC from Salmonella typhimurium, respectively. These
      aptamers were hybridized with thiol-conjugated 16 dT-linker molecules in order to
      be immobilized on silver surface which was, in advance, fabricated on glass
      slide, using a spin-coating method. To confirm that each aptamers retained its
      specific binding activities to their antigenic live bacteria, microscopic view of
      bound cells immobilized on silver film were observed. Furthermore, we observed
      the fluorescence-emitting bacteria-aptamer complex immobilized on silver film
      after adding RNA aptamers hybridized with fluorophore, FAM-conjugated 16 dT
      linker molecules. As a result, the RNA aptamers-immobilized slide system
      developed in this study was a useful new tool to rapidly monitor individual food
      pathogens.

PMID- 22966535
TI  - Cell chip-based monitoring of toxic effects of cosmetic compounds on skin
      fibroblast cells.
AB  - The present study estimated the efficacy of electrochemical detection of
      imidazolidinyl urea-induced cell toxicity in skin human fibroblast cells (HFF
      cells). The gold nanopunct structures were fabricated through a nanoporous
      alumina mask, and the structural formations were confirmed via scanning electron
      microscopy. The HFF cells were allowed to attach to RGD (Arg-Gly-Asp) peptide
      nanopatterned surfaces, and electrochemical tools were applied to skin cells
      attached to the chip surface. The HFF cells evidenced inflammation responses to
      allergens such as imidazolidinyl urea. The cells were subsequently treated with
      different concentrations of imidazolidinyl urea for 24 h in culture, which
      induced a change in the cyclic voltammetry (CV) current peak. Treatment with
      imidazolidinyl urea induced a loss of cell viability and accelerated inflammation
      in a concentration-dependent manner. The expression level of inflammation-related
      proteins such as IL-1 beta were increased in imidazolidinyl urea-treated cells.
      The CV results demonstrated that imidazolidinyl urea significantly reduced the
      current peaks in a dose-dependent manner. The results showed that the current
      peak was reduced in accordance with the increases in imidazolidinyl urea-induced
      inflammation. In conclusion, the results of this study suggest that the
      electrochemical-based chip provides crucial information for improvements to a
      cell chip system for drug screening applications.

PMID- 22966536
TI  - Kidney-specific peptide-conjugated poly(ester amine) for the treatment of kidney
      fibrosis.
AB  - Kidney gene therapy using the hepatocyte growth factor (HGF) gene may offer new
      strategies for the treatment of chronic renal disease such as kidney fibrosis,
      because HGF has the potential to promote tubular repair and to inhibit tissue
      fibrosis. As a non-viral vector for gene delivery, polyethylenimine (PEI)
      exhibits high gene expression due to its buffering capacity with cytotoxicity,
      although its cytotoxicity depends on its molecular weight. In this study, to
      minimize the cytotoxicity of PEI with a high transfection efficiency,
      biodegradable poly(ester amine) (PEA) based on glycerol dimethacrylate (GDM) and
      low molecular weight PEI (LMW PEI) was synthesized and kidney targeting peptide
      was conjugated to the PEA (PEP-PEA) to give it kidney cell specificity. The PEP
      PEA showed good physicochemical properties as a gene delivery carrier, such as
      DNA condensation ability, protection of the DNA in the complexes from enzyme
      degradation, and formation of nanosized complexes with spherical shapes. Higher
      transfection efficiency in 293T cells was achieved with the PEP-PEA than with the
      PEA and the PEI 25 kDa with lower cytotoxicity. Also, the HGF gene that was
      complexed with the PEP-PEA was specifically delivered to the obstructed kidney in
      the unilateral ureteral obstruction (UUO) model rats. The delivered HGF gene
      exhibited potency in recovering renal functions, which indicates the potential of
      the PEP-PEA as a safe and efficient carrier for the treatment of kidney fibrosis.

PMID- 22966537
TI  - Nanogap-based electrical PNA chips for the detection of genetic polymorphism of
      cytochrome P450 2C19.
AB  - PNA chips for the detection of the genetic polymorphism of Cytochrome P450 2C19
      (CYP2C19), a well-known enzyme related to the metabolism of therapeutic drugs,
      were electrically-interfaced with interdigitated nanogap electrodes (INEs). The
      average gap distance and effective length of the INEs were about approximately 70
      nm and approximately 140/m, respectively. Those INEs having the aspect ratio of
      about 2000, were prepared by the combination of the photolithography (for the
      formation of initial electrodes) and the surface-catalyzed chemical deposition
      (for the gap narrowing), without the e-beam lithography. The PNA probes for the
      detection of CYP2C19 were immobilized in the gap region of INEs via Schiff base
      formation. The I-V characteristics clearly showed a sharp increase in the
      conductance between the nanogap electrodes upon the PNA-DNA hybridization,
      followed by the adsoprtion of functionalized Au nanoparticles. Four different
      target DNAs for the diagnosis of CYP2C19 polymorphism were successfully detected
      and discriminated with the INE-based PNA chips.

PMID- 22966538
TI  - 3-D simulation of nanopore structure for DNA sequencing.
AB  - In this paper, we propose a method for simulating nanopore structure by using
      conventional 3-D simulation tool to mimic the I-V behavior of the nanopore
      structure. In the simulation, we use lightly doped silicon for ionic solution
      where some parameters like electron affinity and dielectric constant are fitted
      to consider the ionic solution. By using this method, we can simulate the I-V
      behavior of nanopore structure depending on the location and the size of the
      sphere shaped silicon oxide which is considered to be an indicator of a DNA base.
      In addition, we simulate an Ionic Field Effect Transistor (IFET) which has
      basically the nanopore structure, and show that the simulated curves follow
      sufficiently the I-V behavior of the measurement data. Therefore, we think it is
      reasonable to apply parameter modeling mentioned above to simulate nanopore
      structure. The key idea is to modify electron affinity of silicon which is used
      to mimic the KCl solution to avoid band bending and depletion inside the
      nanopore. We could efficiently utilize conventional 3-D simulation tool to
      simulate the I-V behavior of nanopore structures.

PMID- 22966539
TI  - Evaluation of interaction between histidine binding Cu2+ ion and histidine by
      atomic force microscopy.
AB  - This paper presents a direct interaction force measurement between histidine
      molecules using AFM force-distance curve measurement. AFM force-distance curves
      between the histidine-modified cantilever and substrate in the different
      conditions with or without intercalating Cu2+ ion were measured and interpreted
      via Gaussian curve fitting analyses. The adhesion force between histidine
      molecules was shown to be 110 pN under the presence of Cu2+. The result was
      compareable to the measured adhesion force about 0 pN, which was measured by the
      removal of Cu2+ ion with the addition of EDTA. The result indicated the direct
      histidine-histidie interaction was difficult without the role of the bridigible
      ionic component. From the results, the possibility of direct measurement on
      chemical affinities between biomolecules was suggested by using AFM force
      distance curve analyses. Especially, the current approach showed the possible
      affinity measurement techniques that elucidate the role of bridge ions.

PMID- 22966540
TI  - Study of the primo-vascular system and location-dependent oxygen levels for a
      mouse embryo.
AB  - The two major circulatory systems, the lymph system and the blood vessel system,
      play significant roles in controlling embryonic development. The primo-vascular
      system (PVS) was recently reported as an additional circulatory system in various
      animals. In this paper, the PVS in a mouse embryo was investigated. The
      structural characterization of the PVS in the mouse placenta and umbilical cord,
      which was visualized with the trypan blue staining technique, was focused on. The
      PVS was well_developed in the mouse placenta area. Using a nanopore-based
      amperometric oxygen sensor, the oxygen levels at four different areas of the
      embryonic brain, placenta, blood vessel, and primo-vessel of the PVS were
      measured. The relatively higher oxygen levels that were measured at the primo
      vessels than at the brain and the placenta, while still lower than the oxygen
      level that was measured at the blood vessels, may suggest a role of PVS in oxygen
      transport.

PMID- 22966541
TI  - Immunosensor based on the ZnO nanorod networks for the detection of H1N1 swine
      influenza virus.
AB  - This paper presents an immunosensor fabricated on patterned zinc oxide nanorod
      networks (ZNNs) for detecting the H1N1 swine influenza virus (H1N1 SIV).
      Nanostructured ZnO with a high isoelectric point (IEP, approximately 9.5)
      possesses good absorbability for proteins with low IEPs. Hydrothermally grown
      ZNNs were fabricated on a patterned Au electrode (0.02 cm2) through a lift-off
      process. To detect the H1N1 SIV, the sandwich enzyme-linked immunosorbent assay
      (ELISA) method was employed in the immunosensor. The immunosensor was evaluated
      in an acetate buffer solution containing 3,3',5,5'-tetramethylbenzidine (TMB) via
      cyclic voltammetry at various H1N1 SIV concentrations (1 pg/mL-5 ng/mL). The
      measurement results of the fabricated immunosensor showed that the reduction
      currents of TMB at 0.25 V logarithmically increased from 259.37 to 577.98 nA as
      the H1N1 SIV concentration changed from 1 pg/mL to 5 ng/mL. An H1N1 SIV
      immunosensor, based on the patterned ZNNs, was successfully realized for
      detecting 1 pg/mL-5 ng/mL H1N1 SIV concentrations, with a detection limit of 1
      pg/mL for H1N1 SIV.

PMID- 22966542
TI  - Galactosylation of chitosan-graft-spermine as a gene carrier for hepatocyte
      targeting in vitro and in vivo.
AB  - Polyethyleneimine (PEI) has been described as a highly efficient gene carrier due
      to its efficient proton sponge effect within endosomes. However, many studies
      have demonstrated that PEI is toxic and associated with a lack of cell
      specificity despite high transfection efficiency. In order to minimize the
      toxicity of PEI, we prepared chitosan-graft-spermine (CHI-g-SPE) in a previous
      study. CHI-g-SPE showed low toxicity and high transfection efficiency. However,
      this compound also had limited target cell specificity. In the present study, we
      synthesized galactosylated CHI-g-SPE (GCS) because this modified GCS could be
      delivered specifically into the liver due to hepatocyte-specific galactose
      receptors. The DNA-binding properties of GCS at various copolymer/DNA weight
      ratios were evaluated by a gel retardation assay. The GCS copolymer exhibited
      significant DNA-binding ability and efficiently protected DNA from nuclease
      attack. Using energy-filtered transmission electron microscopy (EF-TEM), we
      observed dense spherical, nano-sized GCS/DNA complexes with a homogenous
      distribution. Most importantly, GCS was associated with remarkably low
      cytotoxicity compared to PEI in HepG2, HeLa, and A549 cells. Moreover, GCS
      carriers specifically delivered the gene-of-interest into hepatocytes in vitro as
      well as in vivo. Our results suggest that the novel GCS described here is a safe
      and highly efficient carrier for hepatocyte-targeted gene delivery.

PMID- 22966544
TI  - Efficient internalization of peptide-conjugated SPIONs in dendritic cells for
      tumor targeting.
AB  - Antigen delivery using nanoparticles becomes useful and novel strategy to develop
      immunotherapeutic approaches against cancer. In the current study, we examined
      the feasibility of SPIONs-mediated delivery of antigenic peptides to local tumor
      for application to cancer immunotherapy. SPIONs carrying murine melanoma
      antigens, hgp100(25-33) were prepared and used to test its efficacy in mouse
      model. Efficient uptake of peptide-conjugated SPIONs by murine dendritic cells
      (DCs) was shown, using NP labeled with the fluorescent dye Furthermore, potential
      targeting effect of SPIONs carrying tumor antigenic peptide was verified in vitro
      and in vivo. Our results demonstrate the feasibility of SPIONs-mediated antigen
      delivery for cancer immunotherapy and highlight the clinical potential of SPIONs
      for future cancer treatment with high efficacy.

PMID- 22966543
TI  - Cell chip to detect effects of graphene oxide nanopellet on human neural stem
      cell.
AB  - The graphene oxide (GO) nanopellet, a potentially useful carbon-based material,
      recently started being applied in cell-based research areas. Its toxicity
      assessment using the neural-stem-cell-based chip has not been thoroughly reported
      yet, though. Herein, a cell chip was fabricated to electrochemically detect the
      toxic effects of GO nanopellets on HBl.F3 cells. The RGD peptide was immobilized
      on the gold electrode surface to enhance the binding affinity of the HBl.F3 cells
      to the electrode surface. A clear redox peak appeared when the HB1.F3 cells were
      analyzed via cyclic voltammetry. The GO nanopellet was analyzed via Raman
      spectroscopy to confirm its distinct structural characteristics that normally
      differ from those of graphite oxide. After GO was added to the HB1.F3 cells,
      differential pulse voltammetry was performed to discover the toxic effects of GO
      nanopellets on HB1.F3 cells. A negative correlation was achieved between the
      concentration of the GO nanopellets and the cell viability, which was verified
      via both MTT assay and a microscopic imaging tool. Thus, these electrochemical
      tools can be usefully applied to the toxicity assessment of various kinds of
      carbon-based materials.

PMID- 22966545
TI  - Scanning electron microscopy study of the effect of the brushing time on the
      human tooth dentin after exposure to acidic softdrinks.
AB  - Scanning electron microscopy (SEM) was used to examine the abrasive and erosive
      potential of the brushing time on the dentin surface eroded by acidic soft drinks
      to suggest an optimized toothbrushing start time after the consumption of cola
      (pH 2.52) in children. Thirty-six non-carious primary central incisors were
      assigned to 12 experimental groups (n = 3) based on the erosive and abrasive
      treatment protocols. Cola exposure was used as the erosive treatment. Three
      brushing durations (5, 15, and 30 sec) and four brushing start times
      (immediately, 30 min, 60 min, and 120 min) after an erosive pre-treatment were
      used for the abrasive treatment. Toothbrushing after exposure to acidic soft
      drinks led to an increase in the open-tubule fraction and microstructural
      changes. Toothbrushing immediately after the erosive pre-treatment showed the
      largest abrasive and erosive potential on the dentin whereas that 60 and 120 min
      after the pre-treatment showed the least abrasive and erosive potential on the
      dentin. Toothbrushing for both 60 and 120 min after the pre-treatment showed
      similar erosive and abrasive potentials on the dentin. The brushing duration
      showed no effect on the erosive and abrasive potential on the dentin. Therefore,
      to achieve the desired tooth surface cleaning and less surface lesion on the
      dentin surface, toothbrushing should be performed at least 1 hour after cola
      consumption. Three-minute brushing after cola consumption is sufficient to
      prevent dental lesions, and prolonged brushing can irritate the gingival tissues.

PMID- 22966546
TI  - In-vivo and in-vitro biocompatibility evaluations of silver nanoparticles with
      antimicrobial activity.
AB  - In this study, the biocompatibility and antimicrobial activity of silver
      nanoparticles (Ag NPs) were evaluated in vitro and in vivo. The cytotoxicity of
      Ag NPs (average diameter: 2-5 nm) against CHO-K1 cells was determined via WST-8
      assay, and their genotoxicity was examined via Salmonella typhimurium reverse
      mutation assay (Ames test). The acute toxicity and intracutaneous reactivity of
      Ag NPs were evaluated using animal models of mice and rabbits, respectively. The
      antibacterial effects of Ag NPs on the Gram (-) bacterial strains of Escherichia
      coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027 and on the Gram (+) bacterial
      strains of Staphylococcus aureus ATCC 6538p and Bacillus subtilius ATCC 6633 were
      determined by measuring the minimum inhibitory concentrations. The Ag NPs were
      highly cytotoxic to the L-929 cells at over 2 ppm but were non-cytotoxic at lower
      than 1 ppm. Moreover, the Ag NPs at 1 ppm or lower did not show genotoxicity,
      acute toxicity and intracutaneous reactivity. It was also found that the Ag NPs
      exerted effective antimicrobial activities on both the Gram (-) and (+) bacterial
      strains within the range from 0.06 to 0.98 ppm for 50% MIC.

PMID- 22966547
TI  - Ophthalmic application of poly(HEMA)s containing nanoparticles and
      dimethylacrylamide.
AB  - High functional ophthalmic lens materials, poly(HEMA-co-MMA)s were prepared by
      the copolymerization of HEMA, MMA, MA, EDGMA, and N,N-dimethylacrylamide in the
      presence of platinum nanoparticles with antimicrobial properties. The hydrophilic
      monomer N,N-dimethylacrylamide has excellent biocompatibility and oxygen
      transmissibility. The combination where platinum nanoparticles were added
      produced a colorless transparent lens. The water contents were in the range of
      36.68-44.08% and the refractive index was measured to be in the range of 1.424
      1.436. Meanwhile, the oxygen transmissibility ranged from 11.13 x 10(-11) to
      17.63 x 10(-11) (cm2/sec) (mlO2/ml x mm Hg) increased with increasing the
      addition ratio of N,N-dimethylacrylamide. The physical properties measurements of
      the produced polymers showed that the nanoparticles did not show significant
      effect on the water content and refractive index of the hydrogel contact lens,
      but the materials effected to reduce oxygen permeability to a certain extent. The
      copolymers have excellent oxygen permeability, indicating that the material can
      be used to fabricate hydrogel contact lenses with high oxygen transmissibility.

PMID- 22966548
TI  - Fabrication of non-enzymatic biosensor based on metallic catalyst-TiO2 hollow
      sphere nanocomposite for determining biomolecules.
AB  - A PtRu@TiO2-hollow nanocomposite for the detection of biomolecules was
      synthesized by chemical reduction. First, poly(styrene-co-vinylphenylboronic
      acid), PSB, was prepared as a template (approximately 250 nm) by surfactant-free
      emulsion polymerization. Second, PSB/TiO2 core-shell spheres were prepared by sol
      gel reaction. Finally, TiO2 hollow spheres (TiO2-H) were then formed after
      removing the PSB template by calcination at 450 degrees C under air atmosphere.
      To prepare the electrocatalyst, PtRu nanoparticles (NPs) were deposited onto the
      TiO2-H surface by chemical reduction. The prepared PtRu@TiO2-H nanocomposite was
      characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD),
      and elemental analysis. A non-enzymatic sensor was fabricated by depositing the
      as-prepared PtRu@TiO2-H nanocomposite on the surface of a glassy carbon electrode
      (GCE), which was prepared by a hand casting method with Nafion solution as a
      binder. The sensor was tested as a biomolecule sensor, especially for the
      detection of glucose and dopamine. The cyclic voltammograms (CV) obtained during
      the oxidation studies revealed that the PtRu@TiO2-H nanocomposite showed better
      catalytic function toward the oxidation of dopamine. The sensing range of the non
      enzymatic sensor for glucose was 5.0-100 mM in a phosphate buffer. The results
      demonstrated the potential usefulness of this bimetallic@TiO2-H bifunctional
      catalyst for biosensor applications.

PMID- 22966549
TI  - Enhanced mobility of neural cells with a transparent electric field stimulator.
AB  - Mobility is one of the important characteristics of living cells. It also plays a
      significant role in therapeutic cell transplantation with target location
      specificity. To enhance cell mobility, a neural cell stimulator was assembled
      with graphenes, which are two-dimensional nanocarbon materials that form a
      transparent electrode over the cover glass in a cell culture dish. This
      transparent stimulator applies electrical field stimulation to the neural cells.
      The advantages of this new transparent electrical field stimulator (TEFS) with a
      graphene electrode include transparency, because few layered graphenes are
      optically transparent, and biocompatibility, because the cover glass is coated
      with laminin. In this paper, it is reported that constant electric field
      stimulation, which is at a specific strength, facilitates the mobility of a
      neural cell and makes the visibility of cellular behavior on the electrode much
      better than that of any other existing cell stimulator that has metal electrodes.
      The strength of the electrical field for stimulating cells varies from 4.5 mV/mm
      to 450 mV/mm. When continuous electric field stimulation was applied for 4 hours
      at the electric field strength of 45 mV/mm, the mobility of the neural cells was
      significantly enhanced compared to the control conditions, wherein there was no
      electric field stimulation. Thus, the feasibility of the TEFS with the
      nanothickness of graphene was tested to modulate the mobility of neural cells in
      vitro. The result suggests that electrical field stimulation could enhance neural
      cell alignment, cell-to-cell coupling, and networks, and may be applied to cell
      transplantation to boost therapeutic effectiveness.

PMID- 22966550
TI  - Electrical impedance simulation and characterization of cell growth using the
      Fricke model.
AB  - For label-free and real-time monitoring of biological cells, electrical impedance
      sensing of the cells attached to the microelectrode has been used. In this
      article, the electrical impedance analysis of the cell growth using the Fricke
      model that consisted of the extracellular resistance parallel to the series
      combination of an intracellular resistance and the membrane-related capacitance
      was investigated. To relate the morphological changes in the cells that
      accompanied the cell growth in the Fricke model parameters, the impedance spectra
      of a cell model were simulated at different cell sizes and cell-cell gaps using
      the finite element method. The simulated results showed that the increase in the
      cell size results in an increment of the extracellular resistance and that the
      decrease in the cell-cell gap leads to an increment of the extracellular
      resistance and a decrement of the capacitance. Based on the theoretical
      relationship between the model parameters and the considered cellular behavior,
      it was shown that the measured impedance spectra of the cells were mostly
      governed by the change in the cell-cell gap at the beginning of the culture time,
      and then by the cell size or the density of the cells that covered the electrode
      surface with a limited area.

PMID- 22966551
TI  - A facile approach to prepare regenerated cellulose/graphene nanoplatelets
      nanocomposite using room-temperature ionic liquid.
AB  - This study presents the preparation of regenerated cellulose (RC)/graphene
      nanoplatelets (GNPs) nanocomposites via room temperature ionic liquid, 1-ethyl-3
      methylimidazolium acetate (EMIMAc) using solution casting method. The thermal
      stability, gas permeability, water absorption and mechanical properties of the
      films were studied. The synthesized nanocomposite films were characterized by
      Fourier transform infrared (FTIR), X-ray diffraction (XRD) and scanning electron
      microscopy (SEM). The T20 decomposition temperature of regenerated cellulose
      improved with the addition of graphene nanoplatelets up to 5 wt%. The tensile
      strength and Young's modulus of RC films improved by 34 and 56%, respectively
      with the addition of 3 wt% GNPs. The nanocomposite films exhibited improved
      oxygen and carbon dioxide gas barrier properties and water absorption resistance
      compared to RC. XRD and SEM results showed good interaction between RC and GNPs
      and well dispersion of graphene nanoplatelets in regenerated cellulose. The FTIR
      spectra showed that the addition of GNPs in RC did not result in any noticeable
      change in its chemical structure.

PMID- 22966552
TI  - Hybrid optical-electrochemical electronic nose system based on Zn-porphyrin and
      multi-walled carbon nanotube composite.
AB  - In this work, we have enhanced the capability of an e-nose system based on
      combined optical and electrochemical transduction within a single gas sensor
      array. The optical part of this e-nose is based on detection of the absorption
      changes of light emitted from eight light emitting diodes (LEDs) as measured by a
      CMOS photo-detector. The electrochemical part works by measuring the change in
      electrical resistivity of the sensing materials upon contact with the sample
      vapor. Zinc-5,10,15,20-tetra-phenyl-21H,23H-porphyrin (ZnTPP) and multi-walled
      carbon nanotube (MWCNT) composite was used as the sensing materials based on its
      good optoelectronic properties. This sensing layer was characterized by UV-Vis
      spectroscopy and atomic force microscope and tested with various VOC vapors.
      Density functional theory (DFT) calculations were performed to investigate the
      electronic properties and interaction energies between ZnTPP and analyte
      molecules. It can be clearly seen that this hybrid optical-electrochemical
      electronic nose system can classify the vapor of different volatile organic
      compounds.

PMID- 22966553
TI  - X Y parallel compliant stage with compact configuration.
AB  - This paper presents a piezo-driven compliant stage for nano positioning with two
      degree-of-freedom parallel linear motions. Nano positioning is one of the most
      important factors in completion of nanotechnologies. It can be accomplished by
      flexure-based compliant stages driven by piezo-actuators. For compact
      configuration, the compliant stage is stacked by two-layered compliant
      mechanisms. The upper layer contains a motion guide mechanism, and the lower
      layer two displacement amplification mechanisms. The motion guide mechanism
      consists of four prismatic-prismatic parallel compliant joint chains for two
      translational motion guides. The displacement amplification mechanism is adopted
      by a flexure-based flextensional amplification mechanism driven by a stack-type
      piezo actuator. Due to the parallel compliant joint chains, the stage has the
      same dynamics in the x and y axes. In this study, through design and analysis,
      the mechanisms were machined via wire electro-discharge machining and are were
      then integrated with two stack-type piezoelectric elements for actuation, and two
      capacitive sensors for ultra-precision displacement measurement. Finally,
      experiments were carried out to demonstrate the performance of the compliant
      stage.

PMID- 22966554
TI  - A wafer-level vacuum package using glass-reflowed silicon through-wafer
      interconnection for nano/micro devices.
AB  - We propose a vacuum wafer-level packaging (WLP) process using glass-reflowed
      silicon via for nano/micro devices (NMDs). A through-wafer interconnection (TWIn)
      substrate with silicon vias and reflowed glass is introduced to accomplish a
      vertical feed-through of device. NMDs are fabricated in the single crystal
      silicon (SCS) layer which is formed on the TWIn substrate by Au eutectic bonding
      including Cr adhesion layer. The WLPof the devices is achieved with the capping
      glass wafer anodically bonded to the SCS layer. In order to demonstrate the
      successful hermetic packaging, we fabricated the micro-Pirani gauge in the SCS
      layer, and packaged it in the wafer-level. The vacuum level inside the packaging
      was measured to be 3.1 Torr with +/- 0.12 Torr uncertainty, and the packaging
      leakage was not detected during 24 hour after the packaging.

PMID- 22966555
TI  - Interface-modified unipolar resistive random access memory (RRAM) structure for
      low-power application.
AB  - An interface-engineered resistive random access memory (RRAM) using bilayer
      transition metal oxide (TMO) is presented for improving unipolar resistive
      switching characteristics. The experiment and simulation data show that better
      resistive switching characteristics and superb uniformity can be realized by
      inserting a thin AIOx insertion layer between the Ir/NiO interface. To elucidate
      the uniformity improvement of our bilayer structure, the conducting-defect
      effects in the resistive cell were also investigated using a random circuit
      breaker (RCB) simulation model. It has been verified that the forming and set
      characteristics are more effectively improved because the conducting-defect ratio
      in the insertion layer region is low, therefore making it more advantageous for a
      filament path controllability. Using the optimal oxygen contents in both the
      insertion layer and the resistive cell, it was confirmed that a significant
      reduction of up to 0.15 mA of the reset current (I(RESET)) is possible compared
      to the conventional cell. These results indicate that new AI insertion has a
      large contribution to the reset and forming processes.

PMID- 22966556
TI  - Dimensional effect of non-polar resistive random access memory (RRAM) for low
      power memory application.
AB  - The relationships between the resistive cell dimension and the related analytical
      parameters such as the forming voltage, set voltage, and reset current were
      investigated to implement high-density and low-power unipolar RRAM. It was shown
      that the formation process in unipolar switching is strongly related to the cell
      dimension in the sub-nm region, not only in terms of its vertical thickness but
      also of its horizontal length, using the numerical simulation method. With the
      optimal cell size having sufficient initial resistance and a low forming voltage,
      the achievement of the greatest feasibility of the high-density low-power RRAM
      will be further accelerated. A numerical simulation was performed using a random
      circuit breaker (RCB) simulation model to investigate the optimal resistive
      switching condition. The on/off resistance ratio increases as the cell area
      decreases at the sub-nm level, and these phenomena are explained in terms of the
      relatively large set resistance change in a very small area due to the conductive
      defect (CD) amount effect in the RCB network model.

PMID- 22966557
TI  - A novel polysilicon field-enhanced nanowire thin-film transistor with the TiN
      hafnia-nitride-vacuum-silicon (THNVAS) structure for nonvolatile memory
      applications.
AB  - A novel poly-Si field-enhanced nanowire (FEN) TFT memory with the TiN-hafnia
      nitride-vacuum-silicon (THNVAS) structure fabricated simply via a sidewall spacer
      formation has been presented. The THNVAS devices with superior memory performance
      were demonstrated by introducing the hafnia as blocking oxide and the vacuum, the
      lowest-k in nature, as tunneling layer. According to the simulation results, the
      memory device with oxide/nitride/vacuum gate dielectric exhibited a higher local
      electric-field of 4.72 x 10(7) V/cm as compared to 2.55 x 10(7) V/cm for the
      conventional oxide/nitride/oxide counterpart. In addition, the electric-field of
      tunneling layer could be further increased to 7.06 x 10(7) V/cm while the
      blocking oxide was substituted for hafnia. The experimental data showed that
      THNVAS possessed a greater threshold voltage shift of 3.75 V in 10 ms at V(GS) =
      12 V, whereas the shift only 2.5 V for THNOS ones. These considerable
      improvements for THNVAS devices could be attributed to the evident field
      enhancement across the vacuum tunneling layer. Furthermore, owing to the empty
      feature of vacuum tunneling layer, the THNVAS demonstrated much-improved
      endurance performance and preferable data retention property. Hence, such
      excellent characteristics of THNVAS will be an attractive nonvolatile memory for
      future system-on-panel and 3-D Flash applications.

PMID- 22966558
TI  - Development of a detection sensor for lethal H2S gas.
AB  - The gas which may be lethal to human body with short-term exposure in common
      industrial fields or workplaces in LAB may paralyze the olfactory sense and
      impose severe damages to central nervous system and lung. This study is concerned
      with the gas sensor which allows individuals to avoid the toxic gas that may be
      generated in the space with residues of organic wastes under 50 degrees C or
      above. This study investigates response and selectivity of the sensor to hydrogen
      sulfide gas with operating temperatures and catalysts. The thick-film
      semiconductor sensor for hydrogen sulfide gas detection was fabricated WO3/SnO2
      prepared by sol-gel and precipitation methods. The nanosized SnO2 powder mixed
      with the various metal oxides (WO3, TiO2, and ZnO) and doped with transition
      metals (Au, Ru, Pd Ag and In). Particle sizes, specific surface areas and phases
      of sensor materials were investigated by SEM, BET and XRD analyses. The metal
      WO3/SnO2 thick films were prepared by screen-printing method. The measured
      response to hydrogen sulfide gas is defined as the ratio (Ra/R,) of the
      resistance of WO3ISnO2 film in air to the resistance of WO3/SnO2 film in a
      hydrogen sulfide gas. It was shown that the highest response and selectivity of
      the sensor for hydrogen sulfide by doping with 1 wt% Ru and 10 wt% WO3 to SnO2 at
      the optimum operating temperature of 200 degrees C.

PMID- 22966559
TI  - Effect of spray process conditions on uniformity of carbon nanotube thin films.
AB  - Industrial use of carbon nanotube (CNT) films is increasing rapidly due to their
      good physical properties and high economic feasibility. Spray coating process is
      one of feasible approaches for large area CNT films. Uniform spray coating is an
      important issue in applications requiring large area conductive films. In the
      present work, we developed a numerical model for the prediction of CNT deposition
      thickness distribution in the spray process and validated the numerical work by
      using experimental data obtained in this study. We investigated the deposition
      thickness distributions according to various process parameters by using the
      numerical model. We found that the pitch of the nozzle path is a key parameter
      affecting the deposition thickness uniformity and that there is optimal pitch
      value for unfirom and productive coating. We also discussed future research
      direction for improved numerical simulation tool. Since the present numerical
      model is also applicable to simulation of spray process on curvy substrate, the
      numerical model could be an imporatnt step toward a powerful simulation tool for
      design and optimization of the nanomaterial spray process.

PMID- 22966560
TI  - Breakdown characteristics of high-side lateral double-diffused metal oxide
      semiconductor devices.
AB  - In this paper, we discuss the breakdown characteristics of an LDMOSFET (Lateral
      Double-diffused Metal Oxide Semiconductor Field Effect Transistor) structure for
      the optimization of engineering parameters such as the gap between the DEEP N
      WELL and the source region and the doping concentration of the N(ADJUST)-layer.
      The fabricated device exhibits the breakdown voltage (BVdss) over 110 V and the
      specific on-resistance as low as 2.20 mOmega cm2. The robust breakdown
      characteristics seem to be due to the migration of the location wherein maximum
      impact ionization occurs from the gate region to the drain side, which was
      confirmed by the numerical simulation which verifies that the maximum impact
      ionization rate of the proposed structure is 2.44 x 10(16) cm(-3) s(-1), while
      that of the conventional structure being 6.69 x 10(19) cm(-3) s(-1).

PMID- 22966561
TI  - Synthesis of TaZnO thin films using combinatorial magnetron sputtering and its
      electrical, structural and optical properties.
AB  - The structural, electrical, and optical properties of tantalium zinc oxide
      (TaZnO) thin films grown using combinatorial magnetron sputtering system were
      investigated. To explore the effects of film thickness and post annealing
      treatment on the properties of the films, we have fabricated TaZnO sample
      libraries having different thicknesses and carried out post annealing treatment.
      Sample libraries fabricated at room temperature showed the resistivity ranged 2.1
      to approximately 7.1 x 10(-3) Omega cm, while the films post annealed at 200
      degrees C under 1 mTorr exhibited the resistivity as low as 1.2 x 10(-3) Omega
      cm. XRD measurements revealed that the film structure was strongly depended on
      the film thickness, showing that the structure was changed from amorphous to
      polycrystalline with increasing the film thickness. Furthermore, it was found
      that figure of merit (0TC), which was determined by T% and Rs of the TaZnO films,
      showed maximum value as the films with a thickness of 230 nm was post-annealed at
      200 degrees C under vacuum of 1 mTorr.

PMID- 22966562
TI  - Fabrication of an inorganic nano structure for a large area via
      electrohydrodynamic lithography (EHL).
AB  - Electrohydrodynamic lithography (EHL) is one of several unusual lithographic
      techniques for fabricating sub-micrometer structures over a large area. EHL uses
      the electrohydrodynamic (EHD) film instability induced by a laterally modulated
      electric field, which allows it to fabricate not only general organic structures
      but also structures of various components, such as diblock copolymers and
      inorganic materials, without contact between the resist and the stamp.
      Furthermore, EHL is a very special lithographic technique in that diverse
      structures are fabricated from one stamp via electric field modulation. The
      electric field is controlled by the replication time, air layer thickness, etc. A
      replicated inorganic structure was demonstrated from a hexagonal hole and line
      arrays. The heat treatment of the replicated pattern was carried out to obtain
      the crystalline phase, after which the samples were characterized via Raman
      spectroscopy. These values were ascertained using field emission scanning
      electron microscopy (FESEM) and atomic force microscopy (AFM). The results will
      be useful in providing a facile route for patterning functional metal oxides over
      a large area. Such a technique can be used to produce photovoltaic cells, memory
      devices, display devices, etc.

PMID- 22966563
TI  - Co-integration of nano-scale vertical- and horizontal-channel metal-oxide
      semiconductor field-effect transistors for low power CMOS technology.
AB  - In order to extend the conventional low power Si CMOS technology beyond the 20-nm
      node without SOI substrates, we propose a novel co-integration scheme to build
      horizontal- and vertical-channel MOSFETs together and verify the idea using TCAD
      simulations. From the fabrication viewpoint, it is highlighted that this scheme
      provides additional vertical devices with good scalability by adding a few steps
      to the conventional CMOS process flow for fin formation. In addition, the
      benefits of the co-integrated vertical devices are investigated using a TCAD
      device simulation. From this study, it is confirmed that the vertical device
      shows improved off-current control and a larger drive current when the body
      dimension is less than 20 nm, due to the electric field coupling effect at the
      double-gated channel. Finally, the benefits from the circuit design viewpoint,
      such as the larger midpoint gain and beta and lower power consumption, are
      confirmed by the mixed-mode circuit simulation study.

PMID- 22966564
TI  - High-performance bottom-gate poly-Si polysilicon-oxide-nitride-oxide-silicon thin
      film transistors crystallized by excimer laser irradiation for two-bit
      nonvolatile memory applications.
AB  - High-performance bottom-gate (BG) poly-Si polysilicon-oxide-nitride-oxide-silicon
      (SONOS) TFTs with single grain boundary perpendicular to the channel direction
      have been demonstrated via simple excimer-laser-crystallization (ELC) method.
      Under an appropriate laser irradiation energy density, the silicon grain growth
      started from the thicker sidewalls intrinsically caused by the bottom-gate
      structure and impinged in the center of the channel. Therefore, the proposed ELC
      BG SONOS TFTs exhibited superior transistor characteristics than the conventional
      solid-phase-crystallized ones, such as higher field effect mobility of 393 cm2/V
      s and steeper subthreshold swing of 0.296 V/dec. Due to the high field effect
      mobility, the electron velocity, impact ionization, and conduction current
      density could be enhanced effectively, thus improving the memory performance.
      Based on this mobility-enhanced scheme, the proposed ELC BG SONOS TFTs exhibited
      better performance in terms of relatively large memory window, high program/erase
      speed, long retention time, and 2-bit operation. Such an ELC BG SONOS TFT with
      single-grain boundary in the channel is compatible with the conventional a-Si TFT
      process and therefore very promising for the embedded memory in the system-on
      panel applications.

PMID- 22966565
TI  - The effect of thermal annealing on pentacene thin film transistor with micro
      contact printing.
AB  - We used micro contact printing (micro-CP) to fabricate inverted coplanar
      pentacene thin film transistors (TFTs) with 1-microm channels. The patterning of
      micro-scale source/drain electrodes without etch process was successfully
      achieved using Polydimethylsiloxane (PDMS) elastomer stamp. We used the Ag nano
      particle ink as an electrode material, and the sheet resistance and surface
      roughness of the Ag electrodes were effectively reduced with the 2-step thermal
      annealing on a hotplate, which improved the mobility, the on-off ratio, and the
      subthreshold slope (SS) of the pentacene TFTs. In addition, the device annealing
      on a hotplate in a N2 atmosphere for 30 sec can enhance the off-current and the
      mobility properties of OTFTs without damaging the pentacene thin films and
      increase the adhesion between pentacene and dielectric layer (SiO2), which was
      investigated with the pentacene films phase change of the XRD spectrum after
      device annealing.

PMID- 22966566
TI  - Characteristics of Al-doped ZnO films grown by atomic layer deposition for
      silicon nanowire photovoltaic device.
AB  - We report the structural, electrical, and optical characteristics of Al-doped ZnO
      (ZnO:Al) films deposited on glass by atomic layer deposition (ALD) with various
      Al2O3 film contents for use as transparent electrodes. Unlike films fabricated by
      a sputtering method, the diffraction peak position of the films deposited by ALD
      progressively moved to a higher angle with increasing Al2O3 film content. This
      indicates that Zn sites were effectively replaced by Al, due to layer-by-layer
      growth mechanism of ALD process which is based on alternate self-limiting surface
      chemical reactions. By adjusting the Al2O3 film content, a ZnO:Al film with low
      electrical resistivity (9.84 x 10(-4) Omega cm) was obtained at an Al2O3 film
      content of 3.17%, where the Al concentration, carrier mobility, optical
      transmittance, and bandgap energy were 2.8 wt%, 11.20 cm2 V(-1) s(-1), 94.23%,
      and 3.6 eV, respectively. Moreover, the estimated figure of merit value of our
      best sample was 8.2 m7Omega(-1). These results suggest that ZnO:Al films
      deposited by ALD could be useful for electronic devices in which especially
      require 3-dimensional conformal deposition of the transparent electrode and
      surface passivation.

PMID- 22966567
TI  - Pattern uniformity in large-area ultraviolet nano-imprinting by a cylindrically
      inflated flexible mold under low pressure.
AB  - This paper shows a novel nano-imprint method with a polydimethylsiloxane (PDMS)
      replica mold that was bonded on a cylindrically inflated polycarbonate (PC) film
      via a low air pressure. The PDMS mold, which was deformed in terms of its
      cylindrical shape, made a line contact with a substrate from the center region
      and the contact region, then expanded gradually to the outside of the substrate
      when the contact force increased. This contact procedure squeezed the resin that
      was dropped on the substrate from the center to the outside, which prevented the
      trapping of air bubbles while the cavities were filled with the patterns on the
      PDMS mold. The main characteristic of the proposed process was that the nano
      imprint can be realized under a low pressure, compared to conventional processes.
      We will show the system that was implemented under the proposed process concept
      and the patterns that were transferred in an ultraviolet curable resin under
      pressure conditions of less than 5 kPa.

PMID- 22966568
TI  - Stress impact of a tensile contact etch stop layer on nanoscale strained NMOSFETs
      embedded with a silicon-carbon alloy stressor.
AB  - For the purpose of enhancing performance in NMOSFETs, inducing an ever increasing
      tensile stress along Si channel direction is beneficial through the use of
      advanced strained engineering. By means of the lattice mismatched SiC with
      different carbon mole fraction, integrated with tensile contact etch stop layer
      (CESL), the obtainment of significant mobility gain is expected. In the present
      research, the stress distribution in NMOSFETs with the combinations of Silicon
      Carbon (SiC) stressor and tensile CESL is systematically studied by using three
      dimensional (3D) finite element analysis (FEA). Width dependency in conjunction
      with different nanoscale gate length is also analyzed. The analysis results
      indicate that the stress impact of SiC stressor resulting from the stress
      component along channel direction on Si region dominates and tensile CESL could
      enhance this effect. Further important is that the vertical stress within
      NMOSFETs, is raised greatly due to tensile CESL through the examined range of
      gate widths, especially for narrower width. Therefore, the predicted results
      reveal excellent mobility gain through such strain engineering.

PMID- 22966490
TI  - Guidelines for the use and interpretation of assays for monitoring autophagy.
AB  - In 2008 we published the first set of guidelines for standardizing research in
      autophagy. Since then, research on this topic has continued to accelerate, and
      many new scientists have entered the field. Our knowledge base and relevant new
      technologies have also been expanding. Accordingly, it is important to update
      these guidelines for monitoring autophagy in different organisms. Various reviews
      have described the range of assays that have been used for this purpose.
      Nevertheless, there continues to be confusion regarding acceptable methods to
      measure autophagy, especially in multicellular eukaryotes. A key point that needs
      to be emphasized is that there is a difference between measurements that monitor
      the numbers or volume of autophagic elements (e.g., autophagosomes or
      autolysosomes) at any stage of the autophagic process vs. those that measure flux
      through the autophagy pathway (i.e., the complete process); thus, a block in
      macroautophagy that results in autophagosome accumulation needs to be
      differentiated from stimuli that result in increased autophagic activity, defined
      as increased autophagy induction coupled with increased delivery to, and
      degradation within, lysosomes (in most higher eukaryotes and some protists such
      as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is
      especially important that investigators new to the field understand that the
      appearance of more autophagosomes does not necessarily equate with more
      autophagy. In fact, in many cases, autophagosomes accumulate because of a block
      in trafficking to lysosomes without a concomitant change in autophagosome
      biogenesis, whereas an increase in autolysosomes may reflect a reduction in
      degradative activity. Here, we present a set of guidelines for the selection and
      interpretation of methods for use by investigators who aim to examine
      macroautophagy and related processes, as well as for reviewers who need to
      provide realistic and reasonable critiques of papers that are focused on these
      processes. These guidelines are not meant to be a formulaic set of rules, because
      the appropriate assays depend in part on the question being asked and the system
      being used. In addition, we emphasize that no individual assay is guaranteed to
      be the most appropriate one in every situation, and we strongly recommend the use
      of multiple assays to monitor autophagy. In these guidelines, we consider these
      various methods of assessing autophagy and what information can, or cannot, be
      obtained from them. Finally, by discussing the merits and limits of particular
      autophagy assays, we hope to encourage technical innovation in the field.

PMID- 22966569
TI  - Novel palladium germanide schottky contact for high performance schottky barrier
      ge MOSFETs and characterization of its leakage current mechanism.
AB  - The leakage current mechanism of Palladium (Pd) germanide Schottky contact on n
      type Ge-on-Si substrate is analyzed in depth. The electric field dependent
      analysis shows that the dominant leakage current mechanism is the Poole-Frenkel
      emission due to the existence of deep level traps in the depletion region of the
      Pd germanide/n-type Ge Schottky diode. The analysis of the dependence of leakage
      current on temperature also shows that the Poole-Frenkel emission and generation
      current are the dominant components below 100 degrees C and that the Schottky
      emission related to thermionic emission of majority carriers over a potential
      barrier is the main cause of this dominance at high temperature region.

PMID- 22966570
TI  - Spray coating of carbon nanotube on polyethylene terephthalate film for touch
      panel application.
AB  - From a technical perspective, the major limiting factors for the wide adoption of
      CNT films are the DC conductivity, uniformity of sheet resistance and good
      adhesion of CNT on film substrate. In this study, the effects of sonificator and
      process time on the zeta potential and sheet resistance of the CNT-PET film show
      that although the dispersing power of horn-type sonificator is stronger than that
      of bath-type, the SWCNT solution obtained with horn-type sonificator agglomerates
      faster. Likewise, it has been noted that the SWCNT solutions with low enough zeta
      potentials exhibit higher sheet resistance after making CNT-PET films due to the
      damage to SWCNTs caused by high dispersion force. Since the spray coating of
      SWCNT solution gives the SWCNT-SDS composite layer on PET film after drying, the
      excess SDS should be washed off. The removal of excess SDS was conducted by
      dipping in the 3 N HNO3 and SOCl2 solution and washing with deionized water
      followed by heat treatment in a 120 degrees C convection oven for 30 min. The
      lift-off of SWCNT-SDS composite layer after 40 min dipping in the 3 N HNO3
      solution appeared to be due to the continued permeation leading to swelling of
      the SDS layer by the 3 N HNO3 aqueous solution. It was found that ten times of
      spray coating cycle gave CNT-PET film the sheet resistance of 310 Omega/[square]
      and transmittance of 81%. The TSP made with CNT-PET film exhibited a performance
      equal to the one made with ITO-PET film.

PMID- 22966571
TI  - TCAD simulations for thin film solar cells with nanoplate structures.
AB  - The novel thin film solar cell with a nanoplate structure that can solve the
      conflict between the light absorption and the carrier transport in amorphous
      silicon thin film solar cell was investigated by TCAD simulations. This new
      structure has n-type amorphous silicon nanoplate array on the substrate, and p
      type amorphous silicon-carbon as window layer and intrinsic amorphous silicon as
      absorption layer are sequentially grown along the surface of each n-type
      amorphous silicon nanoplate. Under AM 1.5 G sunlight illumination, the light is
      absorbed along the vertical direction of nanoplate while the carrier transport is
      along the horizontal direction. Therefore, nanoplate with the larger height can
      absorb most of the sunlight. The advantage of this novel structure is that the
      thickness of the solar cell can be used as thin as possible for effective
      transport of photo-generated carriers in comparison with the planer one.

PMID- 22966572
TI  - TiO2 paste formulation for crack-free mesoporous nanocrystalline film of dye
      sensitized solar cells.
AB  - Using a doctor-blade method, a highly viscous titanium dioxide (TiO2) paste was
      deposited on a glass substrate coated with fluorine doped tin oxide (FTO). The
      paste was mainly composed of commercially available TiO2 nanoparticles (P25) and
      hydroxypropyl cellulose (HPC) as organic filler. Varying the content of HPC in
      the TiO2 paste changed the physical properties of the mesoporous TiO2 layer,
      particularly its porosity and surface area. From the quantification of dyes on
      Ti2, layer and the electrochemical impedance spectroscopy (EIS) study of the dye
      sensitized solar cells (DSSCs), the surface area of the TiO2 film was found to
      have decreased. This came with the increase of HPC content while the porosity of
      the film increased, consistent with the concurrent decrease of short-circuit
      current density (Jsc) and efficiency (eta). The increased porosity greatly
      affected the electron transport through the TiO2 film by decreasing the
      coordination number of the TiO2 particles resulting to a decrease of the electron
      diffusion coefficient.

PMID- 22966574
TI  - Carbon nanotubes on fluorine-doped tin oxide for fabrication of dye-sensitized
      solar cells at low temperature condition.
AB  - The multi-walled carbon nanotubes (MWCNTs), electrophoretically deposited on
      fluorine-doped tin oxide (FTO), were employed as charge-collecting channels in
      the TiO2 photoelectrode of dye-sensitized solar cells (DSSCs) fabricated at 200
      degrees C. The CNT-networks at the conducting substrate increased the charge
      collection efficiency of the porous TiO2 film, while the short circuit current
      increased up to ca. 43% under optimized condition. However, the significant
      decrease in the open-circuit voltage (Voc) up to ca. 132 mV resulted in the
      failure of the overall cell efficiency improvement. Findings reveal that the
      transfer process for the back electron is mainly responsible for the significant
      Voc drop when the MWCNTs were deposited at the electron-collecting substrate of
      the photoelectrode. The study demonstrates that electrophoretic deposition of
      MWCNTs on charge collecting substrate would be applicable to introduce an
      effective charge-collecting channel for the fabrication of flexible DSSCs under
      low temperature sintering condition.

PMID- 22966573
TI  - Catalytic conversion of waste particle board to bio-oil using nanoporous
      catalyst.
AB  - The catalytic pyrolysis of waste wood including the particle board was examined
      by pyrolysis gas chromatography/mass spectrometry (Py-GC/MS) to produce bio-oil.
      Three different catalysts with a nanoporous structure, Al-MCM-48, Meso-MFI, and
      Pt-Meso-MFI, were used and their performances were compared. When MCM-48 was
      used, the quality of the bio-oil product was better than that prepared by non
      catalytic pyrolysis but the improvement was limited due to its weak acid sites.
      On the other hand, Meso-MFI, which has both an MFI structure and strong acid
      sites, exhibited much better cracking ability and higher selectivity for
      aromatics. Moreover, Pt-impregnation on Meso-MFI resulted in an even higher
      selectivity for aromatics and phenolics, which are important raw materials in
      various petroleum chemical processes. KEYWORDS: Catalytic Pyrolysis, Py-GC/MS,
      Waste Particle Board, AI-MCM-48, Meso-MFI,

PMID- 22966576
TI  - Magnesium content ratio effects of MgxZn1-xO seed layers on structural and
      optical properties of ZnO nanorods.
AB  - ZnO nanorods were grown on MgxZn1-xO seed layers with different content ratio
      ranging from 0 to 0.3 by hydrothermal method. Scanning electron microscopy (SEM),
      X-ray diffraction (XRD), and photoluminescence (PL) were carried out to
      investigate the effects of Mg content ratio for the MgxZn1-xO seed layers on the
      structural and optical properties of the ZnO nanorods. The surface morphology and
      structural properties of the MgxZn1-xO seed layers were changed by the Mg
      incorporation. However, the appearance, such as density, diameter, and shape, of
      the ZnO nanorods grown on the MgxZn1-xO seed layers was not changed
      significantly. The highest intensity ratio of the near-band-edge emission (NBE)
      to deep-level emission (DLE) and the narrowest full width at half maximum (FWHM)
      of the NBE peaks, indicating improvement in the crystallinity and luminescent
      properties of the ZnO crystals, were observed in the ZnO nanorods grown on the
      MgxZn1_xO seed layers with the content ratio of the 0.05.

PMID- 22966575
TI  - Evaluation of multi-layered graphene surface plasmon resonance-based transmission
      type fiber optic sensor.
AB  - Graphene is a zero band-gap semi-metal with remarkable electromagnetic and
      mechanical characteristics. This study is the first ever attempt to use graphene
      in the surface plasmon resonance (SPR) sensor as replacement material for
      gold/silver. Graphene, comprised of a single atomic layer of carbon, is a purely
      two-dimensional material and it is an ideal candidate for use as a biosensor
      because of its high surface-to-volume ratio. This sensor is based on the
      resonance occasion of the surface plasmon wave (SPW) according to the dielectric
      constants of each metal film and detected material in gas or aqueous phase.
      Graphene in the SPR sensor is expected to enlarge the range of analyte to bio
      aerosols based on the superior electromagnetic properties of graphene. In this
      study, a SPR-based fiber optic sensor coated with multi-layered graphene is
      described. The multi-layered graphene film synthesized by chemical vapor
      deposition (CVD) on Ni substrate was transferred on the sensing region of an
      optical fiber. The graphene coated SPR sensor is used to analyze the interaction
      between structured DNA biotin and Streptavidin is analyzed. Transmitted light
      after passing through the sensing region is measured by a spectrometer and
      multimeter. As the light source, blue light which of 450 to 460 nm in wavelength
      was used. We observed the SPR phenomena in the sensor and show the contrary
      trends between bare fiber and graphene coated fiber. The fabricated graphene
      based fiber optic sensor shows excellent detection sensitivity of the interaction
      between structured DNA and Streptavidin.

PMID- 22966577
TI  - Phenomenological analysis of random telegraph noise in amorphous TiOx-based
      bipolar resistive switching random access memory devices.
AB  - As dimensions of resistive random access memories (RRAMs) devices continue to
      shrink, the low-frequency noise of nanoscale devices has become increasingly
      important in evaluating the device reliability. Thus, we investigated random
      telegraph noise (RTN) caused by capture and emission of an electron at traps. We
      physically analyzed capture and emission processes through systematic
      measurements of amorphous TiOx (alpha-TiOx)-based bipolar RRAMs. RTNs were
      observed during high-resistance state (HRS) in most devices. However, discrete
      switching behavior was scarcely observed in low-resistance state (LRS) as most of
      traps in the alpha-TiOx were filled with mobile ions such as O2- in LRS. The
      capture and emission processes of an electron at traps are largely divided into
      two groups: (1) both capture and emission processes are mainly affected by
      electric field; and (2) one of the capture and emission processes is only
      influenced by the thermal process. This paper provides fundamental physics
      required to understand the mechanism of RTNs in alpha-TiOx-based bipolar RRAMs.

PMID- 22966578
TI  - Electrochemical fabrication of (TMTSF)2X (X = PF6, BF4, CIO4) nanowires.
AB  - TMTSF-based (TMTSF = tetramethyltetraselenafulvalene = C10H12Se4) charge-transfer
      salt nanowires were fabricated using the galvanostatic deposition technique that
      was assisted by an anodic aluminum oxide (AAO) template. By applying a low
      current density of 1-2 microA/cm2 for more than one month, nanowire arrays with
      diameters of approximately 150 nm and lengths of approximately 6 microm were
      obtained. The length of nanowires can be controlled by the duration of the
      constant current application. Energy-dispersive X-ray spectroscopic (EDX)
      analysis confirmed that selenium is one of the main components of the nanowires.
      The micro-Raman (v3C == C) and FT-IR spectra (v3PF6-, v3BF4-, v3CIO4-) indicated
      that the nanowire arrays had the (TMTSF)2X (X = PF6, BF4, CIO4) phase. The TEM
      images and the selected area electron diffraction (SAED) patterns indicate that
      the nanowires were not single crystals, but the current-voltage characteristic
      that was measured with the four-terminal method showed the conductivity of the
      (TMTSF)2PF6 single crystals (sigmaRT = 1.6 S/cm) at room temperature.

PMID- 22966579
TI  - Strain engineering of nanoscale Si P-type metal-oxide-semiconductor field-effect
      transistor devices with SiGe alloy integrated with contact-etch-stop layer
      stressors.
AB  - Strained-silicon (Si) has been incorporated into a leading nanoscale logic
      technology. By means of silicon-germanium (SiGe) alloy stressor embedded in
      source and drain (S/D) region, the performance of P-type metal-oxide
      semiconductor field-effect transistors (PMOSFETs) is effectively enhanced.
      However, when a compressive contact-etch-stop layer (CESL) is combined, the
      stress interaction and relative impacts of SiGe stressor integrated with CESL on
      mobility enhancement has been little reported. Therefore, the research performs a
      three dimensional (3D) stress simulation evaluation based on finite element
      method (FEM) for PMOSFETs with S/D SiGe stressor and compressive CESL. The
      proposed simulation methodology is validated as compared with other technological
      literatures. In additions, the gate width dependency is systematically discussed
      to explore the stress effects on devices. The analysis results indicate that a 
      2.6 GPa CESL would continue boosting the stress magnitude on Si channel region
      except for a gate width smaller than 50 nm. The results are useful for nanoscale
      transistor while selecting a proper CESL in the manufacturing processes of
      advanced logic technologies.

PMID- 22966580
TI  - Fabrication of white light-emitting diodes based on UV light-emitting diodes with
      conjugated polymers-(CdSe/ZnS) quantum dots as hybrid phosphors.
AB  - White light-emitting diodes (LEDs) were fabricated using GaN-based 380-nm UV LEDs
      precoated with the composite of blue-emitting polymer (poly[(9,9-dihexylfluorenyl
      2,7-diyl)-alt-co-(2-methoxy-5-{2-ethylhexyloxy)-1 ,4-phenylene)]), yellow green
      emitting polymer (poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}
      thiadiazole)]), and 605-nm red-emitting quantum dots (QDs). CdSe cores were
      obtained by solvothermal route using CdO, Se precursors and ZnS shells were
      synthesized by using diethylzinc, and hexamethyldisilathiane precursors. The
      optical properties of CdSe/ZnS QDs were characterized by UV-visible and
      photoluminescence (PL) spectra. The structural data and composition of the QDs
      were transmission electron microscopy (TEM), and EDX technique. The quantum yield
      and size of the QDs were 58.7% and about 6.7 nm, respectively. Three-band white
      light was generated by hybridizing blue (430 nm), green (535 nm), and red (605
      nm) emission. The color-rendering index (CRI) of the device was extremely
      improved by introducing the QDs. The CIE-1931 chromaticity coordinate, color
      temperature, and CRI of a white LED at 20 mA were (0.379, 0.368), 3969 K, and 90,
      respectively.

PMID- 22966581
TI  - Optimization of nafion ionomer content using synthesized Pt/carbon nanofibers
      catalyst in polymer electrolyte membrane fuel cell.
AB  - In this study, carbon nanofiber (CNF) was used as a support in which 47.5 wt%
      Pt/CNFs catalyst was prepared by a modified polyol method. The platinum particle
      size and dispersion on the CNFs are approximately 2-4 nm as determined by X-ray
      diffractometry and transmission electron microscopy. The specific surface area
      was approximated as 55.90 m2/g by BET analysis. Electrodes were prepared by the
      spray method and have a size of 5 cm2. A commercial catalyst (TKK, 46 wt% Pt/C)
      was used as the anode and the cathode was Pt/CNFs. Different amounts of Nafion
      ionomer (Aldrich, 5 wt% solution, in the range of 0-20 wt%) were coated on a
      membrane (Dupont, Nafion 212) with 0.4 mg/cm2 of Pt catalyst at the cathode side.
      The resulting polarization, ohmic and mass transfer resistances changed
      significantly based on the Nafion ionomer content. Optimum Nafion ionomer content
      in the 47.5 wt% Pt/CNFs was 5 wt%. The well-dispersed Nafion ionomer was observed
      on the catalyst surface area using SEM-EDAX analysis. A sufficient triple-phase
      boundary was formed by a small amount of Nation ionomer due to the BET surface
      area of the Pt/CNFs.

PMID- 22966582
TI  - Highly efficient blue- and white-organic light-emitting diode based on dual
      recombination zones with a charge control layer.
AB  - Highly efficient blue phosphorescent organic light-emitting diodes are
      investigated using iridium(Ill) bis[(4,6-di-fluorophenyl)-pyridinato
      N,C2']picolinate doped in N,N'-dicarbazolyl-3,5-benzene (mCP) with a charge
      control layer (CCL) as the dual recombination zone (DRZ) system. DRZ with CCL was
      used to form a broad recombination zone and exciton confinement within each
      emission zone. Holes and electrons can be easily transported through the CCL,
      which were a mixed p-type mCP and n-type 2,2',2"-(1,3,5-benzenetryl) tris(1
      phenyl)-1H-benzimidazol, for controlling the carrier movement. The CCL can play a
      role in triplet exciton blocking as expected from high triplet energy levels as
      well. Additionally, a white organic light-emitting diode was fabricated using a
      new phosphorescent orange emitter: bis[2-(2,4-difluorophenyl)pyridinato]iridium 2
      (2-hydroxyphenyl)benzothia zolate doped in DRZ. The white device showed a maximum
      luminous efficiency of 23.15 cd/A, a maximum external quantum efficiency of
      9.56%, and a maximum power efficiency of 13.37 lm/W. It also showed white
      emission with CIEx,y coordinates of (x = 0.33, y = 0.41) at 8 V.

PMID- 22966583
TI  - The pH sensing characteristics of the extended-gate field-effect transistors of
      multi-walled carbon-nanotube thin film using low-temperature ultrasonic spray
      method.
AB  - A novel, simple and low-temperature ultrasonic spray method was developed to
      fabricate the multi-walled carbon-nanotubes (MWCNTs) based extended-gate field
      effect transistors (EGFETs) as the pH sensor. With an acid-treated process, the
      chemically functionalized two-dimensional MWCNT network could provide plenty of
      functional groups which exhibit hydrophilic property and serve as hydrogen
      sensing sites. For the first time, the EGFET using a MWCNT structure could
      achieve a wide sensing rage from pH = 1 to pH = 13. Furthermore, the pH
      sensitivity and linearity values of the CNT pH-EGFET devices were enhanced to
      51.74 mV/pH and 0.9948 from pH = 1 to pH = 13 while the sprayed deposition
      reached 50 times. The sensing properties of hydrogen and hydroxyl ions show
      significantly dependent on the sprayed deposition times, morphologies,
      crystalline and chemical bonding of acid-treated MWCNT. These results demonstrate
      that the MWCNT-EGFETs are very promising for the applications in the pH and
      biomedical sensors.

PMID- 22966584
TI  - A simulation model considering sidewall deposition for the precise prediction of
      the performance of label-free photonic-crystal biosensors.
AB  - Photonic-crystal (PC) structures are used as biosensors that detect the changes
      in the surrounding refractive index due to biomolecular interactions. In this
      study, a method of modeling a PC structure that considers the sidewall deposition
      effect during high-index layer deposition was proposed to precisely predict the
      performance of a label-free PC biosensor. A PC composed of nanoreplicated grating
      and a TiO2 high-index layer was fabricated. To replicate nanograting, a silicon
      mold with a 450 nm pitch and a 100 nm grating height was fabricated via
      photolithography and reactive ion etching. A mold cavity was coated with a self
      assembled monolayer, and UV replication was performed. To realize the PC
      structure, a TiO2 high-index layer was deposited using the E-beam evaporation
      system. To design the simulation model considering the sidewall deposition
      effect, the cross-sectional surface profile of each PC layer was measured.
      Finally, the changes in the transmission spectrum of the fabricated PC structure
      with different buffer solutions were measured and compared with the simulated
      results obtained from rigorous coupled wave analysis to examine the prediction
      accuracy of the proposed simulation model.

PMID- 22966585
TI  - SnO2 nanoparticles distributed on multi-walled carbon nanotubes and ball-milled
      graphite as anode materials of lithium ion batteries.
AB  - SnO2 nanoparticles were supported on ball-milled graphite (BMG) or carbon
      nanotubes (CNTs) using a chemical reduction method with ethylene glycol, and the
      electrochemical properties of the nanocomposites were evaluated as anode active
      materials of lithium-ion batteries. The BMG and CNTs contributed to an increase
      in both the capacity enhancement and cyclic stability compared to that of
      commercial graphite. In particular, the mixture electrode of SnO2/BMG:SnO2/CNT =
      3:1 (in weight ratio) showed higher performance in the reversible capacity and
      cyclic stability than did the SnO2/BMG and SnO2/CNT electrodes. This might be
      resulted from the network formation for excellent electronic path by CNT
      distributed on SnO2/BMG composites.

PMID- 22966586
TI  - Thin film transistor based on TiOx prepared by DC magnetron sputtering.
AB  - This paper reports on the thin film transistor (TFT) based on TiOx prepared by
      direct current (DC) magnetron sputtering for the application of n-type channel
      transparent TFTs. A ceramic TiOx target was prepared for the sputtering of the
      TiO2 films. The structural, optical, and electrical properties of the TiO2 films
      were investigated after their heat treatment. It is observed from XRD measurement
      that the TiO2 films show anatase structure having (101), (004), and (105) planes
      after heat treatment. The anatase-structure TiO2 films show a band-gap energy of
      approximately 3.20 eV and a transmittance of approximately 91% (@550 nm). The
      bottom-gate TFTs fabricated with the TiO2 film as an n-type channel layer. These
      devices exhibit the on-off ratio, the field-effect mobility, and the threshold
      voltage of about 10(4), 0.002 cm2/Vs, and 6 V, respectively. These results
      indicate the possibility of applying TiO2 films depositied by DC magnetron
      sputtering to TiO2-based opto-electronic devices.

PMID- 22966587
TI  - Flexible top-emitting organic light-emitting diodes using semi-transparent multi
      metal layers.
AB  - In this paper, the improved device performance of top-emitting organic light
      emitting diodes (TEOLEDs) with a thin multi-metal layer stack of
      nickel/silver/nickel (Ni/Ag/Ni) and aluminum/silver/aluminum (Al/Ag/Al) that were
      used as the anode and cathode on a flexible substrate is discussed. In
      particular, Indium-Tin-Oxide (ITO) as an anode electrode has been used recently
      even though it has some problems for flexible devices. Therefore we suggested
      that a thin multi-metal layer electrode as a new anode is fabricated instead of
      ITO anode. It was verified that the ITO-free TEOLEDs showed an enhanced
      probability of the recombination of the electrons and holes through an improved
      electron/hole charge balance. We also analyzed the optical and electrical
      characteristics using the current density, luminance, luminance efficiency,
      external quantum efficiency (EQE), CIE x, y coordinates, and EL spectra of
      flexible TEOLED devices were characterized. ITO-free, flexible, green-emitting
      OLEDs with a low cost and a simple process were demonstrated.

PMID- 22966588
TI  - Resistive-switching memory effect of hybrid structures with polyimide and SnO2
      nanocrystals.
AB  - Hybrid memory devices with polyimide and SnO2 nanocrystals on a flexible
      polyethersulphone substrate have shown a memristor behavior from current-voltage
      (I-V) measurements. The resistive-switching effects with a current bistability
      appeared during cycling voltage sweeping within the range of +/- 4 V. This I-V
      switching effect might have originated from a resistance fluctuation due to the
      charge trapping into the SnO2 nanocrystals as well as the oxygen vacancies of the
      ZnO layer and aluminum oxides that were formed between the polyimide and the
      interface of the Al gate electrode. In the bipolar resistance-switching behavior,
      the ratio of the high- and low-resistance state currents was about 3.7 x 10(4) at
      1 V.

PMID- 22966589
TI  - Field-emission stability of hydrothermally synthesized aluminum-doped zinc oxide
      nanostructures.
AB  - The Al-doped ZnO (AZO) nanostructures field-emission arrays (FEAs) were
      hydrothermally synthesized on AZO/glass substrate. The samples with Al-dosage of
      3 at.% show the morphology as nanowires vertically grown on the substrates and a
      structure of c-axis elongated single-crystalline wurtzite. The good field
      emission (i.e., the large anode current and low fluctuation of 15.9%) can be
      found by AZO nanostructure FEAs with well-designed Al-dosage (i.e., 3 at.%)
      because of the vertical nanowires with the less structural defects and superior
      crystallinity. Moreover, the Full width at half maximum (FWHM) of near band-edge
      emission (NBE) decreased as the increase of annealing temperature, representing
      the compensated structural defects during oxygen ambient annealing. After the
      oxygen annealing at 500 degrees C, the hydrothermal AZO nanostructure FEAs
      revealed the excellent electrical characteristics (i.e., the larger anode current
      and uniform distribution of induced fluorescence) and enhanced field-emission
      stability (i.e., the lowest current fluctuation of 5.97%).

PMID- 22966590
TI  - Characterization of the SnO2 based thin film transistors with Ga, In and Hf
      doping.
AB  - We investigated the effects of doping tin oxide thin film transistors (TFTs) with
      Ga, In, and Hf. The quantity of doping impurities added to the SnO2-TFT channel
      layer was as follows: Ga (6.3-21.4 at.%), In (9.6-55.6 at.%), and Hf (1.2-2.7
      at.%). Hafnium and gallium doping of SnO2 thin film decreased the carrier
      concentration, possibly due to a decrease in field effect mobility, and reduced
      oxygen vacancy-related defects. Indium-doped SnO2-TFTs exhibited high performance
      with a high field-effect mobility of > 20 cm2 V(-1) s(-1). The current on/off
      ratio and the subthreshold swing of In-doped SnO2-TFTs was 1 x 10(9) and 0.5
      V/decade, respectively. These results demonstrate that Ga, In, and Hf doping can
      effectively enhance the performance of SnO2-based TFT devices.

PMID- 22966591
TI  - Magnetic, optical and structural property studies of Mn-doped ZnO nanosheets.
AB  - We report the synthesis of pure and Mn doped ZnO in the form of nanosheets using
      a simple and single step procedure involving a microwave assisted chemical
      method. As prepared Mn-doped ZnO nanosheets were characterized using X-ray
      diffraction (XRD), field emission scanning electron microscopy (FESEM),
      transmission electron microscopy (TEM), ultra violet-visible (UV-Vis), Raman
      spectroscopy and magnetization measurements. The structural studies using XRD and
      TEM revealed the absence of Mn-related secondary phases and showed that Mn-doped
      ZnO comprise a single phase nature with wurtzite structure. FESEM and TEM
      micrographs show that the average diameter of Mn-ZnO assembled nanosheets is
      about approximately 50 nm, and the length of a Mn-doped ZnO nanosheet building
      block which is made up of thin mutilayered sheets is around approximately 300 nm.
      Concerning the Raman scattering spectra, the shift in peak position of E2 (high)
      mode toward low frequencies due to the Mn doping could be explained well by means
      of the spatial correlation model. Magnetic measurements showed that Mn-doped ZnO
      nanosheets exhibit ferromagnetic ordering at or above room temperature.

PMID- 22966592
TI  - Impact of strain engineering on nanoscale strained III-V PMOSFETs.
AB  - Stress distributions in the strained InGaAs PMOSFET with source/drain (S/D)
      stressors for various lengths and widths were studied with 3D stress simulations.
      The resulting mobility improvement was analyzed. Compressive stress along the
      transport direction was found to dominate the hole mobility improvement for the
      wide width devices. Stress along the vertical direction perpendicular to the gate
      oxide was found to affect the mobility the least, while stress along the width
      direction enhanced in the middle wide width region. The impact of channel width
      and length on performance improvements such as the mobility gain was analyzed
      using the Kubo-Greenwood formalism accounting for nonpolar hole-phonon scattering
      (acoustic and optical), surface roughness scattering, polar phonon scattering,
      alloy scattering and remote phonon scattering. The novelty of this paper is
      studying the impact of channel width and length on the performance of InGaAs
      PMOSFET such as mobility and exploring physical insight for scaling the future
      III-V CMOS devices.

PMID- 22966593
TI  - Squeezed mode conversion in hybrid plasmon polariton waveguide using spin-coated
      silver film.
AB  - We designed, fabricated, and characterized a hybrid surface plasmon polariton
      waveguide (SPP_wg) for mode conversion. The 20-nm-thick silver SPP_wg was
      fabricated via spin-coating with an aqueous silver ionic complex solution. The
      structure of the SPP_wg consists of a straight Insulator-Metal-Insulator
      waveguide (IMl_wg), a lateral tapered Insulator-Metal-Insulator-Metal-Insulator
      waveguide (tapered_IMIMI_wg), and a straight IMIMI waveguide (IMIMI_wg). An s0
      mode size of 12.90 microm x 8.08 microm at a 6-microm-wide IMI_wg was excited by
      a butt-coupling method at a wavelength of 1550 nm. The s0 mode was converted into
      an Ss0 mode size of 8.08 microm x 5.65 microm at a 3-microm-wide IMIMI_wg. The
      mode size was squeezed by approximately 2/3 via a 15-microm-long lateral
      tapered_IMIMI_wg with a 500-nm-thick central insulator. The coupling loss for
      mode conversion between the straight IMI_wg and the straight IMIMI_wg was 5.49
      dB. The hybrid SPP_wg for mode conversion has the potential to bridge the gap
      between micron and sub-micron scales in nano plasmonic integrated circuits. In
      addition, the use of the spin coating method is very cost-effective because films
      are formed at a low temperature in a short period of time without the need for a
      vacuum system.

PMID- 22966594
TI  - Novel anti-reflection technology for GaAs single-junction solar cells using
      surface patterning and Au nanoparticles.
AB  - Single-junction GaAs solar cell structures were grown by low-pressure MOCVD on
      GaAs (100) substrates. Micro-rod arrays with diameters of 2 microm, 5 microm, and
      10 microm were fabricated on the surfaces of the GaAs solar cells via
      photolithography and wet chemical etching. The patterned surfaces were coated
      with Au nanoparticles using an Au colloidal solution. Characteristics of the GaAs
      solar cells with and without the micro-rod arrays and Au nanoparticles were
      investigated. The short-circuit current density of the GaAs solar cell with 2
      microm rod arrays and Au nanoparticles increased up to 34.9% compared to that of
      the reference cell without micro-rod arrays and Au nanoparticles. The conversion
      efficiency of the GaAs solar cell that was coated with Au nanoparticles on the
      patterned surface with micro-rod arrays can be improved from 14.1% to 19.9% under
      1 sun AM 1.5G illumination. These results show that micro-rod arrays and Au
      nanoparticle coating can be applied together in surface patterning to achieve a
      novel cost-effective anti-reflection technology.

PMID- 22966595
TI  - Improvement of optical extraction efficiency of organic light-emitting diode
      using a large area nano-pattern.
AB  - In order to improve optical extraction efficiencies, we propose a nano-patterned
      organic light-emitting diode (OLED) which doesn't rely on high precision
      lithography nor rigorous periodicity. The nano-pattern is fabricated by spin
      coating PS (poly-styrene) spheres on the substrate and carrying out reactive ion
      etching and flattening using dielectric material. The verification of the optical
      properties of the nano patterns was carried out by fabricating OLED-like
      structures using quantum dot and distributed Bragg reflector (DBR). As a result,
      the nano-patterned structure showed a 28% increase in optical efficiency compared
      to the non-patterned sample. In addition, the use of a prism sheet on the
      backside of a glass substrate also showed a 23% increase in optical efficiency by
      disturbing the total internal reflection between glass and air. In this way, the
      large area nano-patterns can be fabricated and applied to increasing the optical
      extraction in OLED.

PMID- 22966596
TI  - Replication of a thin polydimethylsiloxane stamp and its application to dual
      nanoimprint lithography for 3D hybrid nano/micropatterns.
AB  - This paper presents the fabrication of a thin and flexible polydimethylsiloxane
      (PDMS) stamp with a thickness of a few tens of um and its application to
      nanoimprint lithography (NIL). The PDMS material generally has a low elastic
      modulus and high adhesive characteristics. Therefore, after being treated, the
      thin PDMS stamp is easily deformed and torn, adhering to itself and other
      materials. This paper introduces the use of a metal ring around the flange of a
      thin PDMS stamp to assist with the handling of this material. A PDMS stamp with a
      motheye pattern in nanometer scale was inserted between a substrate and a
      microstamp with concave patterns in micrometer scale. Subsequently, three
      dimensional (3D) hybrid nano/micropatterns were fabricated by pressing these two
      stamps and curing the resist. The fabricated hybrid patterns were measured and
      verified in both the microscale and nanoscale. The process, termed "dual NIL,"
      can be applied to the fabrication of optical components or bio-sensors that
      require repetitive nanopatterns on micropatterns.

PMID- 22966597
TI  - The effects of radio frequency plasma power on Ai2O3 films deposited at room
      temperature by remote plasma atomic layer deposition.
AB  - Al2O3 films were deposited by a remote plasma atomic layer deposition (RPALD)
      method at room temperature (25 degrees C) in a reactor using alternating
      exposures of Al(CH3)3 and O2 plasma. Oxygen plasma was used as a reactant gas to
      decompose the trimethylaluminum [TMA, Al(CH3)3] precursor at room temperature.
      The RF plasma power was increased to produce enough radicals for the deposition
      of the Al2O3 films at room temperature. Then, changes in the interfacial and bulk
      properties of the deposited Al2O3 films were investigated according to increasing
      RF power. Al2O3 films deposited by RPALD with RF powers over 100 W showed similar
      bulk properties, indicating that radicals over a certain threshold did not have a
      decisive effect on the additional decomposition of precursors for a low impurity
      content in the films. An increase in RF plasma power could improve the
      interfacial stability due to an increase in radicals and ions in the plasma and
      the minimization of plasma-induced substrate damage by adopting remote plasma.

PMID- 22966598
TI  - Fabrication of triple-layered magnetite/hydrogel/quantum dots via the molecular
      linkage of bi-functional diamines.
AB  - A multifunctional biomedical agent with magnetism, pH-sensitive, fluorescent
      properties was fabricated as a triple-layered magnetite/hydrogel/quantum dots.
      First, core-shell magnetic silica nanospheres (Fe3O4@SiO2) were synthesized via
      the sol-gel reaction of magnetite clusters with tetraethyl orthosilicate (TEOS),
      and the resuting magnetic particles were encapsulated with poly(N
      isopropylacrylamide-co-acrylic acid) hydrogels through a free radical
      polymerization. The hydrogel-encapsulated magnetic particles were subsequently
      anchored by quantum dots (QDs) via the molecular linkage of bi-functional
      diamines. Diamine molecules effecrively induced the crosslinking between magnetic
      hydrogels and quantum dots. Among diamine linkers with different chain lengths (C
      4, C-8, and C-12), C-8 diamine (1,8-diaminooctane) produced the maximal PL
      intensity for QD-bound hydrogels, indicating that C-8 diamine was an optimal
      cross-linker between hydrogels and QDs with surface carboxylic acid groups. The
      characteristic properties of the multifunctional nanocomposites were analyzed by
      scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT
      IR), zeta-potential meter, and photoluminescence (PL) spectroscopy.

PMID- 22966599
TI  - High-performance polycrystalline silicon thin-film transistors with two
      dimensional location control of the grain boundary via excimer laser
      crystallization.
AB  - High-performance low-temperature polycrystalline silicon (Poly-Si) thin-film
      transistors (TFTs) have been fabricated with two-dimensional (2-D) location
      controlled grain boundaries using excimer laser crystallization (ELC). By locally
      increased thickness of the amorphous silicon (a-Si) film that was served as the
      seed crystals with a partial-melting crystallization scheme, the cross-shaped
      grain boundary structures were produced between the thicker a-Si grids. The Poly
      Si TFTs with one parallel and one perpendicular grain boundary along the channel
      direction could therefore be fabricated to reach excellent field-effect mobility
      of 530 cm2/V-s while the conventional ones exhibited field-effect mobility of 198
      cm2/V-s. Furthermore, the proposed TFTs achieved not only superior electric
      properties but also improved uniformity as compared with the conventional ones
      owing to the artificially controlled locations of grain boundaries.

PMID- 22966600
TI  - Formation of nano-sized Y2O3 dispersoids in mechanically alloyed Ni-(Cr, Y2O3, Y)
      alloys during heat-treatments.
AB  - In the present work, the evolution of nanoparticles during annealing and hot
      consolidation in mechanically alloyed Ni-22Cr-1.5Y, Ni-22Cr-1.5Y2O3 and Ni-3%
      Y2O3 was examined. The high-energy ball-milling of elemental powders resulted in
      the complete dissolution of the constituent Cr, Y, or Y2O3, forming a Ni-based
      solid solution. During the subsequent annealing, however, oxide particles
      precipitated from the solid solution. In the case of mechanically alloyed Ni-22Cr
      1.5Y2O3, over-grown Cr2O3 precipitated at a temperature as low as above
      approximately 500 degrees C and ternary YCrO3 particles precipitated at 1100
      degrees C. In the case of mechanically alloyed Ni-22Cr-1.5Y, on the other hand,
      the binary Y2O3 phase precipitated at 1100 degrees C during spark plasma
      sintering. The presence of Cr in the alloy composition facilitated the formation
      of Cr2O3 or YCrO3, and the precipitated oxides were highly prone to grain growth
      during hot-consolidation, sometimes reaching several micrometers. In Cr-exempt Ni
      3%Y or Ni-3% Y2O3, however, the growth of nanodispersoids was restrained even at
      temperatures as high as 1000 degrees C and the resulting dispersoid was only nano
      sized Y2O3.

PMID- 22966601
TI  - Surface hardening of Al alloys through controlled ball-milling and sintering.
AB  - One of the drawbacks of aluminum and its alloys is the lack of proper heat
      treatment for surface-hardening. In the present work, a new and simple method of
      hardening the surface of aluminum and its alloys was developed. Low-energy ball
      milling using specific process control agents (PCAs) was employed, using
      subsequent sintering in a controlled atmosphere. The PCAs in the present work
      were very effective both for milling and the formation of hard nanocrystalline
      dispersoids during sintering. The residual oxygen in a sintering atmosphere also
      played an important role in the formation of AIN or Al-O-N dispersoids. Through
      the proper control of the processing atmosphere and PCAs, the hardness and
      thickness of the hardened layers could be adjusted. The results of the wear test
      showed that the present aluminum alloys can be effectively utilized as light
      weight components with a good wear resistance. Furthermore, the present method
      involves a simple forming process of die-compaction and sintering.

PMID- 22966602
TI  - Effects of growth parameters on the structural and optical properties of
      InP/InGaP quantum structures for 808-nm-wavelength emissions.
AB  - InP/InGaP quantum structures with 808-nm-wavelength emissions were grown on semi
      insulating GaAs (100) substrates via migration-enhanced molecular beam epitaxy.
      The effects of the growth conditions on the structural and optical properties of
      the InP/InGaP quantum structures were investigated. The scanning electron
      microscopy and atomic force microscopy images showed that the two-dimensional
      InP/InGaP quantum structures were transited to one-dimensional structures with an
      increasing repetition cycle. The photoluminescence spectra showed that the
      optical properties of the InP/InGaP quantum structures were significantly
      affected by various migration-enhanced epitaxy repetition numbers and growth
      temperatures. These results can help improve understanding of the effects of
      growth parameters on the structural and optical properties of InP/InGaP quantum
      structures for 808-nm-wavelength emissions.

PMID- 22966603
TI  - Microwave assisted hydrothermal synthesis and magnetocaloric properties of
      La0.67Sr0.33MnO3 manganite.
AB  - We report microwave assisted hydrothermal synthesis and magnetocaloric properties
      of La0.67Sr0.33MnO3 manganite. The synthesized La0.67Sr0.33MnO3 nanoparticles was
      characterized using X-ray diffraction (XRD), field emission scanning electron
      microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS) and magnetization
      measurements. The XRD results indicated that La0.67Sr0.33MnO3 nanoparticles have
      polycrystalline nature with monoclinic structure. FE-SEM results suggested that
      La0.67Sr0.33MnO3 nanoparticles are assembled into rod like morphology.
      Magnetization measurements show that La0.67Sr0.33MnO3 nanoparticles exhibit
      transition temperature (Tc) above room temperature. The maximum magnetic entropy
      change (deltaS(M))max was found to be 0.52 J/kg K near Tc approximately 325 K at
      applied magnetc field of 20 kOe. This compound may considered as potential
      material for magnetic refrigeration near room temperature.

PMID- 22966604
TI  - Finite-difference time-domain numerical simulation study on the optical
      properties of silver nanocomposites.
AB  - The effects of the nanoparticle geometry and the host matrix on the optical
      properties of silver (Ag) nanocomposites were investigated. The spatial intensity
      distribution and absorption spectra were obtained by solving Maxwell equations
      using the finite-difference time-domain method. Local enhancement of the optical
      field was produced near the surface of the Ag nanoparticle. As the nanoparticle
      size increased, the plasmon-induced absorption increased and the surface plasmon
      resonance (SPR) wavelength of the Ag nanocomposite was redshifted. As the
      nanoparticle geometry was transformed from a sphere to an ellipsoid, two plasmon
      peaks appeared and their spectral spacing became larger with increasing the
      aspect ratio. The effects of the nanoparticle size and the anisotropic geometry
      on the optical properties of the Ag nanocomposites can be described by the
      Maxwell-Garnett theory and the Drude model. From the absorption spectra of the Ag
      nanocomposites with five different host matrices (SiO2, Al2O3, ZnO, ZrO2, and
      TiO2), it was found that the SPR wavelength of the Ag nanocomposite was
      redshifted with increasing the refractive index of the host matrix.

PMID- 22966605
TI  - Electrical characteristic analysis using low-frequency noise in low-temperature
      polysilicon thin film transistors.
AB  - This study carried out an electrical characteristic analysis using low-frequency
      noise (LFN) in top gate p-type low-temperature polysilicon thin film transistors
      (LTPS TFTs) with different active layer thicknesses between 40 nm and 80 nm. The
      transfer characteristic curves show that the 40-nm device has better electrical
      characteristics compared with the 80-nm device. The carrier number fluctuation,
      with and without correlated mobility fluctuation model in both devices, has
      modeled well the measured noise. On the other hand, the trap density and coulomb
      scattering in the 40-nm device are smaller compared with the 80-nm device. To
      confirm the effectiveness of the LFN noise analysis, the trap densities at a
      grain boundary are extracted using in both devices the similar methods of Proano
      et al. and Levinson et al. That is, coulomb scattering, caused by the trapped
      charges at or near the interface, has a greater effect on the device with
      inferior electrical properties. Based on the LFN and the quantitative analysis of
      the trap density at a grain boundary, the interface traps between the active
      layer and the gate insulator can explain the devices' electrical degradation.

PMID- 22966606
TI  - A molecular keypad lock that uses Cu(II) cations and H2PO4- anions as inputs.
AB  - Molecular keypad lock devices have considerable advantages over simple molecular
      logic gates because the output signals not only depend on the proper combination
      of inputs but also on the sequence of the input signals. Especially, keeping in
      view the role played by transition metal ions, anions and electronic devices in
      day to day life, the development of applications in electronic devices upon
      chemical inputs of these cations or anions in a sequential manner is very
      important. Previously, we designed a 2, 2'-dihydroxyazobenzene (DHAB)-based model
      of a keypad lock system depending on the inputs sequence of Zn(ll) cations and
      H2PO4- anions. In the present work, we studied the properties of 2-((E)-(2-((E)-3
      bromoallyloxy)phenyl)diazenyl)phenol, compound 1, toward anions in the absence
      and presence of Cu(ll) cations, in order to further explore the potential
      applications of DHAB-based sensing systems. We demonstrated that the application
      of compound 1 with the inputs of Cu(ll) cations and H2PO4- anions could be
      realized as a molecular keypad lock which could be of future interest in
      molecular computing.

PMID- 22966607
TI  - Low-power-Consumption metal oxide NO2 gas sensor based on micro-heater and screen
      printing technology.
AB  - An NO2 micro gas sensor was fabricated based on a micro-heater using tin oxide
      nano-powders for effective gas detection and monitoring system with low power
      consumption and high sensitivity. The processes of the fabrication were
      acceptable to the conventional CMOS processes for mass-production. Semiconducting
      SnO2 nano-powders were synthesized via the co-precipitation method; and to
      increase the sensitivity of the NO2 gas rare metal dopants were added. In the
      structure of the micro-heater, the resistances of two semi-circular Pt heaters
      were connected to the spreader for thermal uniformity. The resistance of each
      heater becomes an electrically equal Wheatstone-bridge, which was divided in half
      by the heat spreading structure. Based on the aforementioned design, a low-power
      consumption micro-heater was fabricated using the CMOS-compatible MEMS processes.
      A bridge-type micro-heater based on the Si substrate was fabricated via surface
      micro-machining. The NO2 sensing properties of a screen-printed tin oxide thick
      film device were measured The micro gas sensors showed substantial sensitivity
      down to 0.5 ppm NO2 at a low power consumption (34.2 mW).

PMID- 22966608
TI  - Aptamer-based immunosensor on the ZnO nanorods networks.
AB  - This paper presents the fabrication and characteristics of a new aptamer-based
      electrochemical immunosensor on the patterned zinc oxide nanorod networks (ZNNs)
      for detecting thrombin. Aptamers are single-stranded RNA or DNA sequence that
      binds to target materials with high specificity and affinity. An antibody-antigen
      aptamer sandwich structure was employed to this immunosensor for detecting
      thrombin. First, hydrothermally grown ZNNs were patterned on the patterned 0.02
      cm2 Au/Ti electrodes on a glass substrate by lift-off process. The high
      isoelectric point (IEP, approximately 9.5) of nanostructured ZnO makes it
      suitable for immobilizing proteins with low IEP. Then 5 microL of the 500 nM
      antibody was immobilized on the ZNNs electrode. 5 micro/L of the mixture of 1
      microM aptamer labeled by ferrocene (Fc) and thrombin was dropped on the
      electrode for antibody-antigen binding. The peak oxidation currents of the
      immunosensors at various thrombin concentrations were measured by using cyclic
      voltammetry. The peak oxidation current was observed at 340 mV versus Ag/AgCl
      electrode, and the peak oxidation current increased linearly from 62.26 nA to
      354.13 nA with the logarithmic concentration of thrombin in the range from 100 pM
      to 250 nM. Fabrication of an aptamer-based immunosensor for thrombin detection is
      a new attempt and the characteristics of the fabricated immunosensors showed that
      the fabricated aptamer-baded immunosensor worked electrochemically well and had a
      low detection limit (approximately 91.04 pM) and good selectivity.

PMID- 22966609
TI  - Ohmic contact effect of Ag-nanodots on quantum efficiency of Si solar cell.
AB  - The authors investigated Si solar cell with the inclusion of nano-Ag dots using
      the ink-jet printer. These nano-Ag dots were used for the Ohmic contact layer on
      phospho-silicate glass layer, which was not removed after the formation of Si
      emitter layer by phosphorus diffusion process. The SiNx layer deposited on the
      nano-Ag dots shows the catalyst selective growth and so the layer formed beneath
      of nano-Ag dots. The photoreflectances show that the long wavelength from 360 nm
      to 1200 nm tends to be increased as the density of the nano-Ag is increased. In
      case of short wavelength from 294 nm to 367 nm, it shows the opposite trend,
      indicating the plasmon effect of the nano-Ag. As embedding the nano-Ag dots on
      the phospho-silicate glass layer, the blocked Ohmic contact was opened and the
      quantum efficiency of 14.4% was achieved, which is higher than the reference
      sample of 12.72% without the glass layer. The nano-Ag dots form the good Ohmic
      contact and also enhance the light conversion efficiency with the formation of
      surface plasmon.

PMID- 22966610
TI  - Formation of CuInSe2 absorber layers formed using co-electrodeposition combined
      with selenization.
AB  - Stoichiometric CuInSe2 absorber layers were formed using co-electrodeposition
      coupled with selenization. We investigated the influence of the metal ion ratio,
      supporting electrolyte, and deposition voltages on the structural and chemical
      properties of Cu-In alloys. The increases in deposition voltage and metal ion
      concentration helped to form In-rich Cu-In alloy with dendrite structure composed
      of a long central trunk with secondary branches. In addition, on increasing the
      concentration of the supporting electrolyte, the ratio of In to Cu in the Cu-In
      alloy increased, and surface morphology improved. Finally, based on an optimized
      co-electrodeposition process, the selenization of Cu-In alloys using the
      evaporation of the Se element was employed to form high quality CuInSe2 absorber
      layers.

PMID- 22966611
TI  - Pore control using the nano structured powders on the fabrication of porous
      membrane and its application.
AB  - In this study, a catalytic membrane with controlled pore size and structure was
      fabricated with nano sized particles and used in a steam and dry reforming
      reaction. The catalytic membrane was made using uniaxial-pressing and thermal
      treatment of the mixed powder. Nano sized yttria stabilized ZrO2 added to the
      nickel powder was determined to be a key factor in the preparation of the
      catalytic membrane. The membrane did not show the sintering effect due to the
      hindering of nickel agglomeration when subjected to heat treatment at high
      temperature. The optimum yttria stabilized ZrO2 content was below 1 wt% due to
      its strength and porosity. It was also unnecessary to deposit an additional
      reforming catalyst on the catalytic membrane, since the surface nickel site
      displayed excellent catalytic activity. When a mixture of methane and
      water/carbon dioxide was fed into the YSZ-Ni catalytic membrane reactor, the
      activity trended exceeded the performance of a conventional catalyst reactor,
      because of the difference in the flux of the gases.

PMID- 22966612
TI  - Donor and acceptor dynamics of phosphorous doped ZnO nanorods with stable p-type
      conduction: photoluminescence and junction characteristics.
AB  - We employed temperature-dependent photoluminescence (PL) to explain the donor and
      acceptor dynamics in phosphorus doped stable p-type P:ZnO nanorods. The room
      temperature PL revealed good crystalline and optical quality of P:ZnO nanorods.
      The 10 K PL spectrum exhibited a dominant acceptor bound exciton (A0X) or donor
      bound exciton (D0X) emission corresponding to p- and n-type P:ZnO nanorods,
      respectively. The donor-acceptor-pair (DAP) transitions exhibited different
      thermal dissociation energies for the p- and n-type P:ZnO nanorods, suggesting
      their different quenching channels. The quenching of the DAP transitions of the p
      type ZnO:P nanorods was associated with the thermal dissociation of the DAP into
      free excitons, while the DAP transition of the n-type ZnO:P nanorods was quenched
      through the thermal dissociation of the shallow donor into free electrons. The
      rectifying behavior of a p-n homojunction diode formed by the p-type P:ZnO
      nanorods on n-type ZnO film confirmed the p-type conduction of the P:ZnO
      nanorods.

PMID- 22966613
TI  - Effect of thermal annealing on the efficiency of heterojunction photovoltaic
      cells fabricated using poly(3-hexylthiophene) and methanofullerene, [6,6]-phenyl
      C61-butyric acid methyl ester.
AB  - The effects of thermal annealing on the efficiency of heterojunction photovoltaic
      (PV) cells that were fabricated using poly(3-hexylthiophene) (P3HT) and
      methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester (PCBM) were
      investigated. The absorption spectra showed that the absorption intensity of the
      P3HT:PCBM layer that was annealed for 5 min had the highest value among the
      several samples with different annealing temperatures. The atomic force
      microscopy image showed that the P3HT:PCBM layer that was annealed for 5 min had
      the best surface morphology. The X-ray photoelectron spectroscopy demonstrated
      that the P3HT:PCBM layer that was annealed at 140 degrees C for 10 min enhanced
      the PCBM aggregation on the surface Al layer that was covered by the P3HT:PCBM
      layer. The efficiencies of the PV cells that were annealed at 3, 5, and 10 min
      were approximately 2.7, 4.2, and 3.5%, respectively. Based on the experiment
      results, the variations in the efficiency of the PV cells due their thermal
      treatment were described.

PMID- 22966614
TI  - High efficiency GaN-based light emitting diode with nano-patterned ZnO surface
      fabricated by wet process.
AB  - The improvement of the optical output power of GaN-based light emitting diodes
      (LEDs) was achieved by a novel bi-layer transparent top electrode scheme. The
      proposed bi-layer structure is composed of a Ga-doped ZnO layer with nano
      patterns obtained solely by wet etching process and an Indium Tin Oxide p-type
      transparent conducting electrode layer. We employed various wet-etching
      conditions to maximize light extraction efficiency and it was observed that the
      crystal morphologies of nano-patterns and optoelectronic properties are dependent
      on etching duration. Because of ITO under GZO layer, the current spreading was
      not affected even after formation of nano-patterned surface on the GZO layer by
      wet etching. Consequently, an enhancement of as high as 43.1% in optical output
      power at an injection current of 100 mA for the LED with nano-patterns wet-etched
      by 0.025% HCl for 30 seconds was realized without significant degradation in
      electrical property when compared to a reference LED.

PMID- 22966615
TI  - Electro-optical characteristics of ZrO2 nanoparticle doped liquid crystal on ion
      beam irradiated polyimide layer.
AB  - It is well known that doping liquid crystals (LCs) with nanoparticles can readily
      change the physical and electro-optical properties of LC mixture. In this paper,
      we report on how the electro-optical properties and thermal stability of an LC
      system were enhanced by dispersing zirconia (ZrO2) nanoparticles in nematic LCs
      on ion-beam irradiated polyimide layers. Homogeneous LC alignment was achieved
      and ZrO2/LC mixture was applied in twisted-nematic (TN) mode. The addition of
      ZrO2 nanoparticles contributed to improvement of electro-optical properties in
      the TN LC cell by lowering voltage operation and decreasing response time. The TN
      LC cells with a ZrO2 nanoparticle concentration of 2.0 wt% showed the lowest
      threshold voltage of 2.0 V and the fastest response time of 15.3 ms. This
      enhanced electro-optical performance was likely due to van-der waals interactions
      and the screening effect of the ZrO2 nanoparticles in the LC medium. The thermal
      stability of the ZrO2/LC mixture was also improved compared to a pristine LC
      system.

PMID- 22966616
TI  - A novel fabrication method for the nanoscale tunneling field effect transistor.
AB  - Tunneling Field Effect Transistors (TFETs) are considered as a candidate for low
      power applications. However, most of TFETs have been researched on only for long
      channels due to the misalignment problem that occurs during the source/drain
      doping process in device fabrication. Thus, a new method is proposed for the
      fabrication of TFETs in nanoscale regions. This proposed fabrication process does
      not need an additional mask to define the source/drain regions, and makes it
      possible to form a self-aligned source/drain doping process. In addition, through
      TCAD simulation, the electrical characteristics of a TFET with dopant engineering
      and a rounded gate edge shape for a higher on/off current ratio were
      investigated. As a result, the TFET showed the properties of a larger on-current,
      a lower average subthreshold swing (58.5 mV/dec), and a 30-fold smaller leakage
      current compared to the conventional TFET The TFET with dopant engineering and a
      rounded gate edge shape can also be fabricated simply through the proposed
      fabrication process.

PMID- 22966617
TI  - Effects of Al concentration on microstructural characteristics and electrical
      properties of Al-doped ZnO thin films on Si substrates by atomic layer
      deposition.
AB  - Al-doped ZnO (AZO) thin films with various Al concentrations were synthesized on
      Si(001) substrates with native oxide layers by atomic layer deposition process.
      The effects of the Al concentration on the microstructural characteristics of the
      AZO thin films grown at 250 degrees C and the correlation between their
      microstructural characteristics and electrical properties of the AZO thin films
      were investigated by AFM, XRD, HRTEM and Hall measurements. The XRD and HRTEM
      results revealed that the crystallinity and electrical properties of the undoped
      ZnO thin films were enhanced by 2.48 at% Al doping. However, 12.62 at% Al doping
      induced the deterioration of their crystallinity and electrical properties due to
      the formation of nano-sized metallic Al clusters and randomly oriented ZnO-based
      nano-crystals. To enhance the electrical properties of the AZO thin films while
      maintaining their crystallinity and electrical properties, a moderate Al
      concentration has to be chosen under the solubility limit of Al in ZnO.

PMID- 22966618
TI  - Thin transparent W-doped indium-zinc oxide (WIZO) layer on glass.
AB  - Annealing effect on structural and electrical properties of W-doped IZO (WIZO)
      films for thin film transistors (TFT) was studied under different process
      conditions. Thin WIZO films were deposited on glass substrates by RF magnetron co
      sputtering technique using indium zinc oxide (10 wt.% ZnO-doped In2O3) and WO3
      targets in room temperature. The post annealing temperature was executed from 200
      degrees C to 500 degrees C under various O2/Ar ratios. We could not find any big
      difference from the surface observation of as grown films while it was found that
      the carrier density and sheet resistance of WIZO films were controlled by O2/Ar
      ratio and post annealing temperature. Furthermore, the crystallinity of WIZO film
      was changed as annealing temperature increased, resulting in amorphous structure
      at the annealing temperature of 200 degrees C, while clear In2O3 peak was
      observed for the annealed over 300 degrees C. The transmittance of as-grown films
      over 89% in visible range was obtained. As an active channel layer for TFT, it
      was found that the variation of resistivity, carrier density and mobility
      concentration of WIZO film decreased by annealing process.

PMID- 22966619
TI  - Laser marking on microcrystalline silicon film.
AB  - We present a compact dot marker using a CW laser on a microcrystalline silicon
      (Si) thin film. A laser annealing shows a continuous crystallization
      transformation from nano to a large domain (> 200 nm) of Si nanocrystals. This
      microscale patterning is quite useful since we can manipulate a two-dimentional
      (2-D) process of Si structural forms for better and efficient thin-film
      transistor (TFT) devices as well as for photovoltaic application with uniform
      electron mobility. A Raman scattering microscope is adopted to draw a 2-D mapping
      of crystal Si film with the intensity of optical-phonon mode at 520 cm(-1). At a
      300-nm spatial resolution, the position resolved the Raman scattering spectra
      measurements carried out to observe distribution of various Si species (e.g.,
      large crystalline, polycrystalline and amorphous phase). The population of
      polycrystalline (poly-Si) species in the thin film can be analyzed with the
      frequency shift (delta omega) from the optical-phonon line since poly-Si
      distribution varies widely with conditions, such as an irradiated-laser power.
      Solid-phase crystallization with CW laser irradiation improves conductivity of
      poly-Si with micropatterning to develop the potential of the device application.

PMID- 22966620
TI  - Phosphorescence color tuning of oxadiazole-based iridium(III) complexes for
      organic light emitting diode.
AB  - The new heteroleptic iridium complexes bearing 2-(5-phenyl-1,3,4-oxadiazol-2
      yl)phenolate (ODZ), were synthesized and characterized for application to organic
      light-emitting diodes (OLEDs). As main ligands (C^N), the anions of 2
      phenylpyridine (ppy), 2-phenylquinoline (pq) and 2-(2,4-difluorophenyl)pyridine
      (F2-ppy) were chelated to the iridium center and 2-(5-phenyl-1,3,4-oxadiazol-2
      yl)phenolate (ODZ) was introduced as an ancillary ligand for luminescence
      modulation of their iridium complexes. We expected that the relative energy
      levels of the main and ancillary ligands in the complexes could lead to emission
      color tuning and luminous efficiency improvement by possible inter-ligand energy
      transfer (ILET). The photoabsorption, photoluminescence and electroluminescence
      of the complexes were studied. Ir(F2-ppy)2(ODZ), Ir(ppy)2(ODZ) and Ir(pq)2(ODZ)
      exhibited the photoluminescence maxima between 505-610 nm at room temperature in
      CH2Cl2, depending on both main and ancillary ligands. The longer pi conjugation
      in the cyclometallating pq ligands leads to the bathochromic shift in
      luminescence of their iridium complexes. The electroluminescent properties of the
      complexes were influenced by ILET.

PMID- 22966621
TI  - Inclusion of CdSe quantum dots on the P-doped emitter of Si solar cells.
AB  - We investigated Cadium Selenide quantum dots embedded in the Si solar cell in
      order to improve the efficiency of conventional Si solar cell. CdSe quantum dots
      with 3 to approximately 4 nm size were printed on the phospho-silicate glass
      layer grown over the emitter surface of p-n junction Si solar cells during the
      phosphorous diffusion process. Ohmic contact was formed by the contribution of
      nanoparticles at the Si emitter in spite of the existance of phospho-silicate
      glass layer. The enhanced light absorption due to the quantum dots was ranged
      from 500 to 600 nm where the CdSe nanodots have the corresponding emission
      wavelength of 560 nm. The efficiency of reference solar cell with the glass layer
      was measured to be 1.0% and it was increased to 12.72% for the reference sample
      without the glass layer. Furthermore, the efficiency of CdSe quantum dot sample
      was measured to be 13.6%. This indicates that the quantum dots play the roles of
      both the formation of tunneling channel and the enhancement of the light
      conversion efficiency in the visible spectral range.

PMID- 22966622
TI  - Effect of the annealing ambient on the electrical characteristics of the
      amorphous InGaZnO thin film transistors.
AB  - The influence of the thermal annealing on the amorphous indium gallium zinc oxide
      (a-IGZO) thin-film transistors (TFTs) under different ambient gases has been
      systematically addressed. The chemical bonding states and transfer
      characteristics of a-IGZO TFTs show evident dependence on the annealing ambient
      gas. For the a-IGZO TFTs in the oxygen ambient annealing at 250 degrees C for 30
      mins exhibited a maximum field effect mobility (max muFE) of 9.36 cm2/V x s,
      on/off current ratio of 6.12 x 10(10), and a subthreshold slope (SS) of 0.21
      V/decade. Respectively, the as-deposited ones without annealing possess a max
      muFE of 6.61 cm2/V x s, on/off current ratio of 4.58 x 10(8), and a SS of 0.46
      V/decade. In contrast, the a-IGZO TFTs annealed at 250 degrees C for 30 mins in
      the nitrogen ambient would be degraded to have a max muFE of 0.18 cm2/V x s,
      on/off current ratio of 2.22 x 10(4), and a SS of 7.37 V/decade, corresponding.
      It is attributed to the content of the oxygen vacancies, according the x-ray
      photoelectron spectroscopy (XPS) analyze of the three different samples.

PMID- 22966623
TI  - Thermal stability of atomic layer deposited Ru layer on Si and TaN/Si for barrier
      application of Cu interconnection.
AB  - The thermal stability of thin Ru single layer and Ru/TaN bilayers grown on bare
      Si by plasma enhanced atomic layer deposition (PEALD) have been studied with
      Cu/Ru, Cu/Ru/TaN structures as a function of annealing temperature. To
      investigate the characteristics as a copper diffusion barrier, a 50 nm thick Cu
      film was sputtered on Ru and Ru/TaN layers and each samples subjected to thermal
      annealing under N2 ambient with varied temperature 300, 400, and 500 degrees C,
      respectively. It was found that the single 5 nm thick ALD Ru layer acted as an
      effective Cu diffusion barrier up to 400 degrees C. On the other hand ALD Ru (5
      nm)/TaN (3.2 nm) showed the improved diffusion barrier characteristics even
      though the annealing temperature increased up to 500 degrees C. Based on the
      experimental results, the failure mechanism of diffusion barrier would be related
      to the crystallization of amorphous Ru thin film as temperature raised which
      implies the crystallized Ru grain boundary served as the diffusion path of Cu
      atoms. The combination of ALD Ru incorporated with TaN layer would be a promising
      barrier structure in Cu metallization.

PMID- 22966624
TI  - Concentration and temperature effect on controlling pore size and surface area of
      mesoporous titania by using template of F-68 and F-127 co-polymer in the sol-gel
      process.
AB  - Mesoporous titania with crystalline pore walls and controlled pore sizes was
      fabricated through triblock copolymer (pluronic series) templated sol-gel process
      by changing the copolymer concentration and by adjusting their calcination
      temperature. Compared with mesoprous silicate, the synthetic condition of
      mesoporous titania would be sensitive to calcination temperature. Their pore
      arrangement and pore size depend strongly on the concentration of copolymer used
      as a template. Their arrangement of pores and specific surface area increases
      with the increase of calcination temperature up to critical limit, 320 degrees C.
      Beyond the critical temperature, the orderness of pores and specific surface area
      decreases due to the collapse of the pore walls. The specific surface area, pore
      size and pore orderness can be controlled by optimizing calcination temperature
      as well as polymer concentration. We demonstrate the mechanism of pore formation
      and their collapse in the sol-gel synthesis of mesoporous titania.

PMID- 22966625
TI  - Effect of organic buffer layer in the electrical properties of amorphous-indium
      gallium zinc oxide thin film transistor.
AB  - In this research, we reported on the fabrication of top-contact amorphous-indium
      gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) with an organic buffer
      layer between inorganic gate dielectric and active layer in order to improve the
      electrical properties of devices. By inserting an organic buffer layer, it was
      possible to make an affirmation of the improvements in the electrical
      characteristics of a-IGZO TFTs such as subthreshold slope (SS), on/off current
      ratio (I(ON/OFF)), off-state current, and saturation field-effect mobility
      (muFE). The a-IGZO TFTs with the cross-linked polyvinyl alcohol (c-PVA) buffer
      layer exhibited the pronounced improvements of the muFE (17.4 cm2/Vs), SS (0.9
      V/decade), and I(ON/OFF) (8.9 x 10(6)).

PMID- 22966626
TI  - Hardness variation with indenter sharpness in an Au thin-film.
AB  - The effects of the indenter shape on hardness were studied from thin-film
      nanoindentations. Two Berkovich indenters with different operating histories were
      prepared and their morphologies were measured with an atomic force microscope.
      The curvature radii of both indenters that were measured through an image
      analysis were 58.8 nm and 732.2 nm, respectively. The nanoindentations were
      carried out on a 1.2 microm-thick Au thin-film with a Nanoindenter XP system with
      both indenters. Various nanoindentation data with indenter exchanges were
      surveyed, and they showed that the peak indentation loads under the blunter
      indenter were higher than those of the sharper indenter at the same indentation
      depths. The indenter sharpness parameter was used to correct the raw
      nanoindentation curves. The corrected curves overlapped well and the resulting
      hardness values were consistent regardless of the indenter sharpness. The
      intrinsic hardness values of the Au thin-film from both indenters agreed with
      each other, with only a 0.6% difference. This means the indenter sharpness was
      properly corrected and that the sharpness must be considered when the contact
      properties are measured at shallow indentations.

PMID- 22966627
TI  - Synthesis and characterization of vertically aligned carbon nanotube forest for
      solid state fiber spinning.
AB  - Continuous carbon nanotubes (CNT) fibers were directly spun from a vertically
      aligned CNT forest grown by a plasma-enhanced chemical vapor deposition (PECVD)
      process. The correlation of the CNT structure with Fe catalyst coarsening,
      reaction time, and the CNTs bundling phenomenon was investigated. We controlled
      the diameters and walls of the CNTs and minimized the amorphous carbon deposition
      on the CNTs for favorable bundling and spinning of the CNT fibers. The CNT fibers
      were fabricated with an as-grown vertically aligned CNT forest by a PECVD process
      using nanocatalyst an Al2O3 buffer layer, followed by a dry spinning process.
      Well-aligned CNT fibers were successfully manufactured using a dry spinning
      process and a surface tension-based densification process by ethanol. The
      mechanical properties were characterized for the CNT fibers spun from different
      lengths of a vertically aligned CNT forest. Highly oriented CNT fibers from the
      dry spinning process were characterized with high strength, high modulus, and
      high electrical as well as thermal conductivities for possible application as
      ultralight, highly strong structural materials. Examples of structural materials
      include space elevator cables, artificial muscle, and armor material, while
      multifunctional materials include E-textile, touch panels, biosensors, and super
      capacitors.

PMID- 22966628
TI  - Fast and simple reduction of graphene oxide in various organic solvents using
      microwave irradiation.
AB  - The fabrication of graphene has been widely studied and chemical reduction is
      considered the most suitable approach to achieve large-scale production and
      graphene functionalization due to its versatility of chemical routes. We report
      here a fast and simple reduction of graphene oxide in various organic solvents
      using microwave irradiation. The reduction can be completed in several minutes,
      and the oxygen content and conductivity (10,000 S/m) of the reduced graphene
      oxide were comparable to the previously reported results which reported between 1
      hr and 24 hrs for the reduction. We also found that an amide group containing a
      solvent like NMP or DMF reduced graphene oxide (GO) more effectively than did
      other solvents. Further, free radicals generated from NMP significantly enhanced
      deoxygenation of graphene oxide. Moreover, this approach is a non-toxic and
      environmentally-friendly method to obtain highly conductive reduced GO for a wide
      range of applications including graphene-based composites, batteries, and
      electrodes for super-capacitors.

PMID- 22966629
TI  - Optimizing control of Fe catalysts for carbon nanotube growth.
AB  - One must control the size distribution of catalyst Fe nano-particles (NPs) very
      carefully if one is to have any chance of growing "super-aligned" carbon nanotube
      (CNT) forests which can be spun directly into yarns and pulled directly into long
      sheets. Control of the Fe Nps size is important during all phases, including: the
      catalyst deposition, annealing and forest growth. As a result, it is important to
      understand how NPs are affected by various experimental factors as well as how
      those catalyst NPs then cause the growth of the forests. This paper focuses on
      two key experimental factors: The as-deposited thickness of the Fe catalyst film
      and the use of hydrogen gas (H2) during anneal and growth. We found that the
      sheet resistance (Rs) of as-deposited Fe films is directly related to the average
      film thickness and can be used to estimate whether the films can catalyze the
      growth of super-aligned forests. The height of the CNT forests decrease with
      decreasing Rs, but only slowly. More importantly, CNTs grown on the largest and
      the smallest Rs films are less aligned. Instead, they are more curled and wavy
      due to the Fe NP dynamics. The use of Hydrogen (H2) affects the formation of Fe
      NPs from the as-deposited film as well as their composition during the forest
      growth. We find that the addition of H2 to a CNT forest growth process at 680
      degrees C (C2H2/He [30/600 sccm]) increases the CNT alignment substantially. H2
      can also reduce iron-oxides which otherwise would impede the formation of NPs. As
      a result, H2 has multiple roles: besides its chemical reactivity, H2 is important
      for catalyst reconstruction into NPs having a proper size distribution as well as
      surface density.

PMID- 22966630
TI  - Pt nanoparticle-reduced graphene oxide nanohybrid for proton exchange membrane
      fuel cells.
AB  - A platinum nanoparticle-reduced graphene oxide (Pt-RGO) nanohybrid for proton
      exchange membrane fuel cell (PEMFC) application was successfully prepared. The Pt
      nanoparticles (Pt NPs) were deposited onto chemically converted graphene
      nanosheets via ethylene glycol (EG) reduction. According to the powder X-ray
      diffraction (XRD) pattern and transmission electron microscopy (TEM) analysis,
      the face-centered cubic Pt NPs (3-5 nm in diameter) were homogeneously dispersed
      on the RGO nanosheets. The electrochemically active surface area and PEMFC power
      density of the Pt-RGO nanohybrid were determined to be 33.26 m2/g and 480 mW/cm2
      (maximum values), respectively, at 75 degrees C and at a relative humidity (RH)
      of 100% in a single-cell test experiment.

PMID- 22966631
TI  - Reliability evaluation of nano-bi/silver paste sensor electrode for detecting
      trace metals.
AB  - The reliability of sensor characteristics for a nano-bismuth (Bi)/silver (Ag)
      paste electrode has been investigated by comparison with Hg/Bi film electrodes in
      terms of accuracy and precision. Using Ag paste instead of carbon paste as a
      conducting layer, the sensitivity and detection limit of the sensor electrode
      were more enhanced due to a lower electrical conductivity of Ag. For the
      evaluation of detecting ability, the Zn, Cd, and Pb ion concentrations of the
      prepared standard solutions were experimentally measured on Hg film, Bi film, and
      nano-Bi electrodes using anodic stripping voltammetry. A nano-Bi electrode can
      detect Zn, Cd, and Pb ions at 0.1 ppb with higher precision and accuracy compared
      with Hg film and Bi film electrodes. From the trace analyses of Zn, Cd, and Pb
      ions in commercial drinking water and river water using a nano-Bi electrode and
      inductively coupled plasma (ICP) technique, it was concluded that the nano-Bi
      electrode exhibited excellent sensing characteristics with high reliability, and
      could detect even traces of Zn, Cd, and Pb ions that were not detected by the ICP
      method.

PMID- 22966632
TI  - Size and surface modification effects on the pH response of Si nanowire field
      effect transistors.
AB  - We investigated the effects of Si nanowire (SiNW) dimensions and their surface
      modifications on the pH-dependent electronic transport characteristics of SiNW
      Electrolyte-insulator-Semiconductor Field-Effect Transistors (EISFETs). The
      threshold voltages, Vth's, of all devices were extracted from the Id-Vg
      characteristics with Vg applied to the reference electrode immersed in different
      pH solutions, and their pH-dependences were analyzed for various devices. We
      found that our devices produce the systematic pH-dependence of Vth with respect
      to the SiNW's length and show significant changes in a linear pH region and a pH
      sensitivity upon the Si surface modifications. Particularly in the case of the
      APTES-treated surface, the linear variation was observed in the wide region of pH
      = 2 to approximately 11 with the sensitivity of 54.7 +/- 0.6 mV/pH. Also we
      compared our data to a theoretical result based on the Gouy-Chapmam-Stern-Graham
      model and found a reasonable agreement between them.

PMID- 22966633
TI  - Nano-scale stick-slip friction model for the chatter scratch generated by
      chemical mechanical polishing process.
AB  - Although Chemical Mechanical Planarization (CMP) process is a still promising
      technology for the fabrication of the next generation devices, CMP-induced
      defects tackle further development of CMP process. In particular, even nano-sized
      scratches generated by CMP process kill the device directly. However mechanism of
      scratch formation was not clearly understood yet. CMP-induced scratches are
      classified as razor, chatter mark and skipping scratch. Among them, chatter mark
      scratch (or chatter scratch) is the most critical defect for the device yield
      loss. Chatter scratch has a periodic pattern of scars, which is reminiscent of a
      stick-slip friction pattern. Based on that similarity, stick-slip model was
      proposed in this paper in order to explain how chatter scratch is formed. And
      controlling parameters for chatter scratch are defined. During stick period the
      friction force that exceeds the yield strength of wafer surface makes chatter
      scratch and the distance between chatter marks is determined by slip period.

PMID- 22966634
TI  - Electronic structures and carrier distributions of T-shaped AlxGa1-xAs/AlyGa1-yAs
      quantum wires fabricated by a cleaved-edge overgrowth method.
AB  - The electronic structures and carrier distributions of T-shaped AlxGa1_xAs/AlyGa1
      yAs quantum wire (QWR) consisting of crossed arm and stem wells were numerically
      calculated by using a finite-difference method (FDM). The electronic subband
      energies in the arm and the stem wells were numerically calculated by using the
      FDM taking into account two-band Hamiltonian systems considering with and without
      strain and nonparabolicity effects. The band deformation due to strain and the
      probabilistic electron confinement of T-shaped AlxGa1-xAs/AlyGa1-yAs QWRs were
      also calculated. The transition energy from the ground heavy-hole state (HH1) to
      the ground electron state (E1) was 1.584 eV when the strain was not considered
      and 1.585 eV when the strain effects were included. The excitonic peak energies
      corresponding to the interband transitions (E1-HH1) in the T-shaped QWRs
      determined from the photoluminescence spectra were compared favorably with those
      determined from the FDM calculations.

PMID- 22966635
TI  - A study on the correlation between the grain size and the conversion efficiency
      of Mc-Si solar cells.
AB  - For grain size estimation, a prototype system was developed by integrating a
      vision-acquiring hardware and a vision-assistant-processing module based on the
      platform software package of LabVIEW, to systematically estimate the average
      grain size of solar-grade multicrystalline (mc)-Si wafers. Three groups of 156 x
      156 mm mc-Si wafers were selected to produce the average grain sizes of 3.4 mm
      (Group 1), 3.8 mm (Group II), and 4.6 mm (Group III), and were used for the
      fabrication of mc-Si solar cells by employing the standard mc-Si cell fabrication
      procedure of the 30 MW mass production line. The conversion efficiency including
      Jsc and Pmax, showed a quasi linear dependence on the mean grain size, with a
      correlation factor of 0.525%/mm. By combining the EL image and the grain
      size/position-dependent EQE spectra in a wavelength range of 400-1100 nm, the
      conversion efficiency of uniformly-surface-texturized mc-Si solar cells with
      larger grain sizes can be made much higher as a result of the much-reduced
      spatial density of the nano/microscope grain boundaries acting as recombination
      centers or traps.

PMID- 22966636
TI  - Effect of inorganic nanoparticle addition to the hole-collecting buffer layers in
      polymer solar cells.
AB  - We investigated the influence of nickel oxide (NiO) nanoparticles that are
      incorporated into the hole-collecting buffer layer [poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)] on the performance of
      polymer:fullerene solar cells. To understand the optimum composition of NiO
      nanoparticles, the composition of NiO nanoparticles was varied from 0 wt% to 23
      wt%. Results showed that the optical transmittance was gradually decreased as the
      NiO content increased. However, the device performance (short circuit current
      density, fill factor, series resistance, power conversion efficiency) exhibited a
      two stage trend in a boundary of approximately 9 wt% NiO content. This trend was
      in good agreement with the trend of sheet resistance in the presence of slight
      discrepancy owing to the different charge transport geometry.

PMID- 22966637
TI  - Reflow of phosphorous silicate glass layer formed on textured Si surface in
      crystalline Si solar cells.
AB  - We have investigated the reflow behavior of phosphorus silicate glass (PSG) layer
      formed on textured Si surface using transmission electron microscopy and
      simulation. For conventional wet oxidation process, stress-dependent surface
      reaction and stress-dependent oxidant diffusion led to the oxidation retardation
      in both convex and concave regions of the textured Si surface, respectively.
      However, PSG film formed by POCl3-diffusion underwent reflow, resulting in the
      formations of thinner and thicker PSG films in convex and concave regions,
      respectively. Simulation results showed that the reflow of PSG films causes
      lateral thermal mismatch stresses to increase and decrease in convex and concave
      regions, respectively.

PMID- 22966638
TI  - Amorphous Mn oxide-ordered mesoporous carbon hybrids as a high performance
      electrode material for supercapacitors.
AB  - A supercapacitor has the advantages of both the conventional capacitors and the
      rechargeable batteries. Mn oxide is generally recognized one of the potential
      materials that can be used for a supercapacitor, but its low conductivity is a
      limiting factor for electrode materials. In this study, a hybrid of amorphous Mn
      oxide (AMO) and ordered mesoporous carbon (OMC) was prepared and characterized
      using X-ray diffraction, transmission electron microscopy, N2/77 K sorption
      techniques, and electrochemical analyses. The findings indicate that the
      electrochemical activities of Mn oxide were facilitated when it was in the hybrid
      state because OMC acted as a pathway for both the electrolyte ions and the
      electrons due to the characteristics of the ordered mesoporous structure. The
      ordered mesoporous structure of OMC was well maintained even after hybridization
      with amorphous Mn oxide. The electrochemical-activity tests revealed that the
      AMO/OMC hybrid had a higher specific capacitance and conductivity than pure Mn
      oxide. In the case where the Mn/C weight ratio was 0.75, the composite showed a
      high capacitance of 153 F/g, which was much higher than that for pure Mn oxide,
      due to the structural effects of OMC.

PMID- 22966639
TI  - Novel heteroleptic ruthenium (II) complex with DPBPZ derivative for dye
      sensitized solar cells.
AB  - Herein, as Ru(II) complex for the dye-sensitized solar cells (DSSCs), we designed
      and investigated a novel heteroleptic ruthenium complex [Ru(dcbpy)(dpbpz)(NCS)2]
      with dpbpz derivative to enhance photovoltaic performance. The density functional
      theory (DFT) and time-dependent density functional theory (TD-DFT) calculations
      were used to gain insight into the factors responsible for photovoltaic
      properties as dye sensitizer. Molecular orbitals analysis confirmed that HOMO of
      [Ru(dcbpy)2(NCS)2] and [Ru(dcbpy)(dpbpz)(NCS)2] are delocalized over the
      ruthenium t2g character with sizable contribution from the NCS ligand orbitals.
      The LUMO of [Ru(dcbpy)2(NCS)2] is localized over the dcbpy moiety. However, LUMO
      of [Ru(dcbpy)(dpbpz)(NCS)2] is localized over the dpbpz moiety and LUMO + 1 is
      localized the dcbpy moiety. Overall, the absorption spectrum of the present Ru
      complex was more broad than that of [Ru(dcbpy)2(NCS)2] known as N3 dye.
      Especially, absorption band in the region between 500 nm and 600 nm was red
      shifted. Moreover, the distance between the HOMO of [Ru(dcbpy)(dpbpz)(NCS)2] and
      the anchoring moiety is longer than that of [Ru(dcbpy)2(NCS)2]. This means that
      [Ru(dcbpy)(dpbpz)(NCS)2] have longer charge-separated lifetime than
      [Ru(dcbpy)2(NCS)2. These results are attributed to the extended pi-conjugation of
      dpbpz moiety. Therefore, we suggest that newly designed [Ru(dcbpy)(dpbpz)(NCS)2]
      heteroleptic ruthenium complex would be a good candidate as a dye sensitizer of
      DSSCs, comparable to [Ru(dcbpy)2(NCS)2].

PMID- 22966640
TI  - Effects of mechanical ball milling with active gases on hydrogen adsorption
      behaviors of graphite flakes.
AB  - This study examined the effects of the mechanical milling conditions on the
      hydrogen adsorption behaviors of graphite flakes under different gas streams. A
      ball mill technique with various gas streams during treatments was used to
      introduce oxygen-containing functional groups on the graphite surfaces. The
      structural properties of graphite were evaluated by XRD, and the surface
      properties and textural properties were observed SEM, FT-IR, XPS and N2/77 K
      adsorption isotherms. The hydrogen adsorption behavior of the graphite flakes
      were evaluated using a volumetric method at room temperature and 100 atm. The
      mechanically-milled graphite flakes under an oxygen stream showed a higher
      concentration of oxygen functional groups and greater hydrogen adsorption
      capacity than that of graphite flakes under an argon stream. This suggests that
      oxygen functional groups have good chemical affinity with hydrogen molecules in
      this system.

PMID- 22966641
TI  - Novel DCM-based organic dye with a heteroleptic dual-electron donor for dye
      sensitized solar cells.
AB  - A new DCM-based organic dye with a heteroleptic dual electron donor was designed
      and its electronic and optical properties were investigated theoretically for dye
      sensitized solar cells (DSSCs). In this study, heteroleptic Dab dye was compared
      with other homoleptic dyes (Daa and Dbb). To gain insight into the factors
      responsible for photovoltaic efficiency, density functional theory (DFT) and time
      dependent density functional theory (TDDFT) calculations of these dyes were
      conducted. It showed that Dab dye is available as a photovoltaic device from the
      energy diagram for the TiO2 electrode and the iodide electrolyte. It also showed
      that although Dab dye produces slightly stronger absorption at above 600 nm, Dbb
      dye would show a better overall absorption property. Owing to the strong electron
      density and high proximity of its anchoring carboxylic group to LUMO + 1 and
      LUMO, however, it is expected that Dab dye with a heteroleptic dual donor will
      show a competitive performance compared to other dyes with homoleptic dual donors
      in the conversion efficiency for DSSCs.

PMID- 22966642
TI  - Enhanced performance of SubPC/C60 solar cells by annealing and modifying surface
      morphology.
AB  - The performance effect of organic solar cells with subphthalocyanine
      (SubPC)/fullerene (C60) bilayer was investigated with thermal treatment while
      changing the vacuum deposition rate of SubPC. The thermal annealing at 100
      degrees C increases the optical absorption intensity of SubPC film at the
      spectral range of 550-630 nm. The X-ray diffraction (XRD) patterns indicates that
      the thermally annealed film formed the much-ordered morphology, as compared to
      the non-annealed film. Consequently, thermally treated solar cell exhibited
      almost 10% higher power conversion efficiency (PCE) compared to the non-annealed
      device. The fill factor (FF) and PCE of the devices were increased as the
      deposition rate of SubPC was increased up to 5 A/s and then saturated at higher
      deposition rates (> 5 A/s). The surface roughness of SubPC films, measured with
      an atomic force microscope, increased from 1.1 to 5 nm as the deposition rate
      increased from 1 to 7 A/s. These results imply that rough surface increases the
      interfacial area between SubPC and C60 and thereby improves the separation of
      photogenerated electron and hole pairs at the SubPC/C60 interface.

PMID- 22966643
TI  - Photocurrent characteristics of solution-processed mercury sulfide nanoparticles-
      thin films on plastic substrates.
AB  - In this study, we synthesize mercury sulfide (HgS) nanoparticles (NPs) by the
      colloidal method and investigate the optoelectronic characteristics of the
      resulting HgS NPs-thin films on plastic substrates in air at room temperature.
      The HgS NPs with a size of about 6-nm show quantum confinement effects in the
      absorption and photoluminescence spectra of the HgS NPs-thin film. The flexible
      optoelectronic device is constructed with the HgS NPs-thin film on finger
      pattered Au electrodes. When 325-nm wavelength light is irradiated on the HgS NPs
      thin film, charge carriers are photogenerated and transported by the hopping
      mechanism, thereby giving birth to a photocurrent in the film. The photocurrent
      efficiency at a bias voltage of 5 V is estimated to be 1.6 microA/W x cm2 and the
      photocurrent efficiency in the 1000 cycles-bending test changes by less than one
      order of magnitude compared to its initial value before bending.

PMID- 22966644
TI  - Resistive switching characteristics of Cu/ZnO0.4S0.6/Al devices constructed on
      plastic substrates.
AB  - In this study, Cu/ZnO0.4S0.6Al devices are fabricated on plastic substrates using
      the sputtering method at room temperature. The ratio of O/S in the zinc
      oxysulfide thin film is confirmed to be 0.4/0.6 from the Auger depth profiling.
      The Cu/ZnO0.4S0.6/Al devices show unipolar resistive switching behaviors and the
      ratio of the measured resistance in the low-resistance state (LRS) to that in the
      high-resistance state (HRS) is above 10(4). The conduction mechanism of the LRS
      is governed by Ohm's law. On the other hand, in the HRS, the conduction mechanism
      at low voltages is controlled by Ohm's law, but that at high voltages results
      from the Poole-Frenkel emission mechanism. The Ohmic and Poole-Frenkel conduction
      mechanisms observed in the LRS and HRS support the filament model of unipolar
      resistive switching. The memory characteristics of the Cu/ZnO0.4S0.6/Al devices
      are retained for 10(4) sec without any change.

PMID- 22966645
TI  - Synthesis and characterization of new donor-acceptor type copolymers based on
      fluorene derivatives for photovoltaic solar cells.
AB  - In this paper, we demonstrated the successful synthesis of newly designed
      copolymers, C1 and C2, with donor-acceptor type structure. Both C1 and C2
      copolymers contained 9,9-dioctylfluorene-2,7-bis(trimethyleneboronate) as one
      constructional unit to improve the solubility in common organic solvents. The
      other constructional unit was 2,3-bis(5-bromothiophen-2-yl)acrylonitrile (DTDBAL)
      for C1, while 4,7-dibromobenzo[c][1,2,5]thiadiazole unit, 5,5'-dibromo-2,2'
      bithiophene unit and N1, N1-bis(4-bromophenyl)-N4,N4-bis(4-(2-phenylpropan-2
      yl)phenyl)benzene-1,4-diamine are for C2. We fabricated photovoltaic devices
      based on the C1 and the C2 copolymers with Poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) layer, PC70BM layer,
      TiOx layer, and aluminum (Al) electrode. The bulk heterojuntion photovoltaic
      devices using these copolymers as electron donor and PC70BM as the acceptor
      exhibited good device performances when measured at 100 mW cm-2. The power
      conversion efficiency (PCE) of the C1 device reached 0.45% with Voc, Jsc and FF
      of 0.51, 2.50 and 35%, respectively. The PCE of the C2 device reached 0.34% with
      Voc, Jsc, and FF of 0.56, 2.01 and 30%, respectively.

PMID- 22966646
TI  - Field emission properties of carbon nanotube arrays on the thickness-controlled
      flexible substrate by the pattern transfer process.
AB  - A technigal with the polydimethylsiloxane (PDMS) solution infiltrated into the
      SiOx-coated CNTAs has been utilized to directly transfer the CNTAs away from the
      silicon substrate. The oxide coating layer was utilized to protect the morpholgy
      of as-grown patterned vertical aligmed carbon nanotube (CNTs) arrays. The high
      density plasma reactive ions etching (HDP-RIE) system was used to make the CNTs
      emerge from the surface of the flexible substrate and modify the crystallines of
      CNTs. After the protecting oxide was HDP-RIE-processed for 8 min, the emission
      current properties were enhanced to be 1.03 V/microm and 1.43 V/microm,
      respectively, for the turn-on field and the threshold field, as compared with
      1.25 V/microm and 1.59 V/microm for the as-grown CNTs, accordingly. The Field
      Emission (FE) enhancement after dry etching could be attributed to the open-ended
      structures and better crystalline.

PMID- 22966647
TI  - Enhanced light output from the nano-patterned InP semiconductor substrate through
      the nanoporous alumina mask.
AB  - A significant enhancement in the light output from nano-patterned InP substrate
      covered with a nanoporous alumina mask was observed. A uniform nanohole array on
      an InP semiconductor substrate was fabricated by inductively coupled plasma
      reactive ion etching (ICP-RIE), using the nanoporous alumina mask as a shadow
      mask. The light output property of the semiconductor substrate was investigated
      via photoluminescence (PL) intensity measurement. The InP substrate with a
      nanohole array showed a more enhanced PL intensity compared with the raw InP
      substrate without a nanohole structure. After ICP-RIE etching, the light output
      from the nanoporous InP substrate covered with a nanoporous alumina mask showed
      fourfold enhanced PL intensity compared with the raw InP substrate. These results
      can be used as a prospective method for increasing the light output efficiency of
      optoelectronic devices.

PMID- 22966648
TI  - Enhanced formation of a confined nano-water meniscus using a 780 nm laser with a
      quartz tuning fork-atomic force microscope.
AB  - Demonstrated herein is the optical-field-induced enhancement of the formation of
      a confined nanowater meniscus using a distance-regulated quartz tuning fork
      atomic force microscope (QTF-AFM) with a 780 nm laser. While a pulled optical
      fiber tip approaches the surface, the laser is suddenly turned on and focuses on
      the front spot of the tip by the shape of the pulled optical fiber, which plays
      the role of an objective lens and induces the gathering effect of the water
      molecules directed to the electromagnetic-field gradient in air. This phenomenon
      facilitates a new boundary condition to form a long-range confined nano-scale
      liquid bridge between the tip and the surface. After the pulling of the optical
      fiber, 20-nm-thick gold was sputtered on the apex (diameter: approximately 100
      nm) of the tip to guide and focus the beam on the spot. The critical power of the
      laser to overcome the barrier for the formation of a new boundary is 100 microW
      at the distance of 22 nm from the substrate.

PMID- 22966649
TI  - Finite element method simulation of the molding process for thermal nano-imprint
      lithography.
AB  - We made a numerical study on the deformation of a viscoelastic polymethyl
      methacrylene (PMMA) resist when a rigid SiO2 stamp with a rectangular line
      pattern is imprinted into the PMMA resist for thermal nano-imprint lithography
      (NIL). The stress distribution in the polymer resist during the molding process
      is calculated by a finite element method (FEM). Our simulation results reveal
      that the asymmetric von Mises stress is distributed over the polymer around the
      external line, which seems to be due to the squeezing flow under the flat space.
      The stress seems to be concentrated at the sidewall close to the centerline of
      the whole structure. Our simulation also reveals that a micro gap is formed
      between the replicated structure and the outer wall of the mold.

PMID- 22966650
TI  - Complete phase transfer of hydrophobic magnetic nanocrystals into aqueous phase.
AB  - The effective phase transfer of hydrophobic nanocrystals synthesized in nonpolar
      solvents into polar solvents remains great challenge for their nanomedicinal
      applications. To resolve this issue, the exsiting strategies for phase transfer
      of nanocrystals in organic solvents use amphiphilic compounds or lipids as
      imperative moieties by ligand exchange and encapsulations. Ligand exchange
      involves by exchanging the hydrophobic molecules with bifunctional compounds and
      small size of molecules is coordinated with functional molecules to increase the
      steric repulsion forces between boundary of water and nanoparticles. However, the
      yield of phase transferred nanocrystals from hydrophobic nonpolar to hydrophilic
      polar phase is exceptionally low, and sometime irreversible desorption of
      replaced ligands leads to agglomeration and aggregation. Also, their intrinsic
      physiochemical properties are easily influenced by surrounding ion species or pH
      when the particles are suspended in phosphate saline buffer (PBS). Moreover,
      conjugation of bioactive molecules often leads to colloidal instability in PBS
      because of the hydrodynamic nature of the amphiphilic molecules on the surfaces
      of nanoparticles. Here we report a robust and simple post-synthetic surface
      modification procedure of hydrophobic nanoparticles to remove the original
      surface-bound carboxylic acid and increase the water-solubility for nanomedicinal
      applications.

PMID- 22966651
TI  - Adhesion characteristics of silver tracks screen-printed on polyimide with an
      environmental reliability test.
AB  - Printable and flexible electronics are increasingly being used in numerous
      applications that are miniaturized, multi-functional and lightweight.
      Simultaneously, reliability issues of the printed and flexible electronic devices
      are getting more attention. The adhesion of screen-printed silver (Ag) tracks on
      a polyimide (PI) film was investigated after two kinds of the environmental
      reliability test: a constant-temperature storage test, and a steady-state
      temperature and humidity storage test. Atmospheric-pressure plasma (APP) was
      adopted on the PI film surface to improve the poor adhesion derived from the
      inherent hydrophobicity. The Ag tracks constructed via screen printing were
      sintered at 250 degrees C for 30 min in air using a box-type muffle furnace. Some
      samples were exposed under 85 degrees C and 85% relative humidity (RH) for
      various durations (24, 72, 168 and 500 h), and others were aged at 85 degrees C
      with same durations to compare the influence of moisture on the adhesion. The
      adhesion of the screen-printed Ag tracks was evaluated by a roll-type 90 degrees
      peel test. The peel strength of the screen-printed Ag tracks decreased by 76.74%
      and 69.88% after 500 h run of the 85 degrees C/85% RH test, and the aging test,
      respectively. The weakest adhesion was 4.98 gf/mm after the 500 h run of the 85
      degrees C/85% RH test. To demonstrate these experimental results, the
      microstructural evolution and chemical bonding states of the interfacial surfaces
      were characterized using a field emission scanning electron microscope (FE-SEM),
      and X-ray photoelectron spectroscope (XPS), respectively.

PMID- 22966652
TI  - In/Ga inter-diffusion in InAs quantum dot in InGaAs/GaAs asymmetric quantum well.
AB  - The Photoluminescence spectra (PL), their temperature and power dependence were
      investigated for the ground state in InAs quantum dots (QDs) embedded in InGaAs
      asymmetric quantum well (Asym. QW). In-atom segregation is well known phenomena
      in such structures, which result in altering the inter-atomic distances; as a
      consequence the thermo-dynamical parameters change as well, namely Debye
      temperature. The bigger value of Debye temperature for the studied sample with
      respect to the corresponding bulk value is attributed to In/Ga inter-diffusion
      during growth. The inter-diffusion process causes non-radiative defects in the
      sample. As a consequence, rapid decrease in the QDs integrated emission intensity
      as the temperature increases was occurred.

PMID- 22966653
TI  - Synthesis of MgO granule and its precursors via common ion effect.
AB  - It is well known that the shape and size of inorganic nanostructures have much
      influence on their optical, electrical and physical properties. MgO is a
      promising material with potential applications in a variety of fields such as
      catalyst support, reinforcing reagent and good component in superconductors. In
      this study, flower-like Mg(OH)2 and cubic MgCO3 have been successfully prepared
      via hydrolysis control of magnesium salt and alkaline solution with common ions
      under hydrothermal condition by the formation of nano-platelets assembly.
      Subsequent calcination converts both Mg(OH)2 and MgCO3 into the corresponding MgO
      granules of similar flower-like and cubic morphology and size to each precursor.
      The physical and chemical properties of MgO and its precursors of Mg(OH)2 and
      MgCO3 are investigated by SEM, XRD, FT-IR, and TGA analysis.

PMID- 22966654
TI  - High-performance ZnO thin-film transistors with location-controlled crystal
      grains fabricated by low-temperature hydrothermal method.
AB  - In this paper, high-performance bottom-gate (BG) thin-film transistors (TFTs)
      with zinc oxide (ZnO) artificially location-controlled lateral grain growth have
      been prepared via low-temperature hydrothermal method. For the proper design of
      source/drain structure of ZnO/Ti/Pt thin films, the grains can be laterally grown
      from the under-cut ZnO beneath the Ti/Pt layer. Consequently, the single one
      vertical grain boundary perpendicular to the current flow will be produced in the
      channel region as the grown grains from the source/drain both sides are impinged.
      As compared with the conventional sputtered ZnO BG-TFTs, the proposed location
      controlled hydrothermal ZnO BG-TFTs (W/L = 250 microm/10 microm) demonstrated the
      higher field-effect mobility of 6.09 cm2/V x s, lower threshold voltage of 3.67
      V, higher on/off current ratio above 10(6), and superior current drivability,
      reflecting the high-quality ZnO thin films with less grain boundary effect in the
      channel region.

PMID- 22966655
TI  - Transparent anti-stain coatings with good thermal and mechanical properties based
      on polyimide-silica nanohybrids.
AB  - In this work, we synthesized polyimide/silica hybrid materials via sol-gel method
      using a fluorinated poly(amic acid) silane precursor and a variety of
      perfluorosilane contents. We studied the influence of a hybrid coating film with
      the following characteristics; hydrophobicity, oleophobicity, optical
      transparency, and surface hardness of the coating films. The hybrid coatings with
      the fluorosilane contents up to 10 wt% are optically transparent and present good
      thermal stability with a degradation temperature of > 500 degrees C as well as a
      glass transition of > 300 degrees C. Both water contact angle and oil contact
      angle increase rapidly with introducing small amount of the fluorosilane in the
      hybrids and reaches the maximum of 115 degrees and 61 degrees, respectively. The
      hardness of the hybrid coatings increases up to 5H with an increase of the FTES
      content in the hybrids. These colorless, transparent, and thermally stable hybrid
      materials could be suitable for applications as anti-stain coatings.

PMID- 22966656
TI  - Evaluation of sulfur and multi-walled carbon nanotube composite synthesized by
      dissolution and precipitation for Li/S batteries.
AB  - An elemental sulfur and multi-walled carbon nanotube (S-MWNT) composite was
      synthesized by dissolving sulfur in ammonium sulfides and then precipitating on
      MWNT. Morphology observation by scanning electron microscopy (SEM) confirmed that
      S-MWNT product was successfully prepared by incorporating sulfur into MWNT
      network. Without additional conducting material, the S-MWNT composite cathodes
      were prepared for electrochemical tests. The properties measured in discharge
      charge cycling test showed that the composite had the initial discharge capacity
      of 1024 mAh g(-1), which is about 61% sulfur utilization. However, in the
      subsequent cycling, the capacities faded. To determine the reason of rapid
      capacity drop, S-MWNT composite cathodes were compared in the cycling tests with
      varying three kinds of electrolytes and the cathode was subjected to physical
      force by rolling. The changes in the cycle performances proved that the
      deterioration of S-MWNT composite cathodes was not related to the electrolytes
      but to physical bonding that may not maintain the conducting path between sulfur
      and MWNT.

PMID- 22966657
TI  - Electronic transport of lateral PtSi/n/n+-Si Schottky diodes.
AB  - We investigated the transport properties of a lateral PtSi/n/n(+)-Si Schottky
      diode prepared on an n-type silicon-on-insulator (SOI) wafer with a special
      attention on the bipolar transport and the surface effect. With applying a back
      gate bias changing from +18 V to -18 V, the unipolar transport behavior switched
      over to the bipolar one, where an enhanced surface recombination rate due to a
      high surface-to-volume ratio produced a current density approximately 3 x 10(3)
      A/cm2 for 2 V bias through a 40 nm-thick and 18 microm-long nanoribbon. The
      recombination time was estimated to be approximately 1 micros from independent CV
      measurements, which is much smaller value than that of a bulk. The local Fermi
      energy level for electrons at the channel center was monitored by an additional
      voltage probe during each I(D)-V(D) measurement and it revealed the intricate
      nature of the bipolar transport manifested by the huge asymmetrical hysteretic
      behavior on a drain bias cycle which is attributed to the charge storage effect
      and asymmetrical junction profiles.

PMID- 22966658
TI  - Investigation of the dielectric function of solution-processed InGaZnO films
      using ellipsometry.
AB  - The optical properties of InGaZnO (IGZO) films grown through the sol-gel process
      as a function of sintering time were investigated with spectroscopic ellipsometry
      (SE). The IGZO precursor sol was prepared by mixing In nitrate, Ga nitrate, and
      Zn acetate at a molar ratio of In:Ga:Zn = 3:1:1. The solution was deposited on a
      SiO2/Si substrate via spin coating. Sintering was performed at 400 degrees C for
      1-15 h in an ambient atmosphere. The optical properties were measured over the
      range 1.12-6.52 eV via variable angle SE, at room temperature. The angle of
      incidence was varied from 50 to 70 degrees in 5 degree steps. To extract the pure
      optical properties of IGZO, multilayer-structure calculation with Tauc-Lorentz
      dispersion relation for IGZO was performed. The changes in the dielectric
      function of the IGZO films with varying sintering time were observed. The
      resultant optical properties can be related to the concentration of oxygen
      vacancies in the material, which can be controlled by the sintering time.

PMID- 22966659
TI  - Radiolytic production of Ag-containing nanocomposite colloids in presence of
      lithium ions.
AB  - This research is motivated to prepare homogeneous and less aggregated
      nanostructured composites for potential scintillators. Poly ethylene glycol (PEG)
      protected approximately 5 nm and approximately 29 nm sized Ag nanoparticles and
      Ag-Zn nanocomposites were relatively prepared by electron-beam irradiation on Ag+
      and Zn2+ solutions with the aids of stabilizers and 6Li+ at room temperature
      under atmospheric pressure. Especially the 6Li+, which was used for a neutron
      absorption purpose, played a part the Ag-Zn nanocolloids to less aggregate in the
      aqueous phase by making partial complexes with stabilizers containing Ag-Zn. To
      be a potential scintillator, the Ag-Zn nanocomposites have to show an optical
      response to radiation. Therefore, optical luminescence, which resembles the
      concept of detecting light without the requirement of a neutron absorbent
      (convertor) for a neutron scitillator, of the nanocomposites was tested.

PMID- 22966660
TI  - Electron transfer properties of iodine-doped single-walled carbon nanotubes using
      field effect transistor.
AB  - Single-walled carbon nanotubes (SWNTs) are known to have a p-type charge transfer
      character in the atmosphere. The energy state of SWNTs can be modulated by doping
      with either an electron donor or an acceptor. In this study, iodine molecules are
      chosen for intercalation to SWNTs to predict the charge transfer tendency between
      them. Field-effect transistors (FETs) using iodine intercalated SWNTs (I-SWNTs)
      are fabricated and their electronic properties are investigated to better
      understand the charge transfer between iodine and SWNTs by changing gate
      voltages. Under vacuum, I-SWNT FETs exhibit weak n-type character, indicating
      that electrons are transferred slightly from the iodine to the SWNTs. After
      exposure to O2 gas, n-type characters are reduced; however, they still retain
      their original type.

PMID- 22966661
TI  - Infrared conductivity and carrier mobility of large scale graphene on various
      substrates.
AB  - It is known that low-field mobility of graphene depends largely on the substrate
      material on which it is transferred. We measured Drude optical conductivity of
      graphene on various substrates and determined the carrier density and carrier
      scattering rate. The carrier density varies widely depending on the substrate
      material. However the scattering rate is almost constant, approximately 100 cm(
      1), for 5 different substrates. We calculate carrier mobility of graphene using
      the two quantities, i.e., carrier density and scattering rate, to find that it
      agrees with the mobility measured from dc transport experiment. We conclude that
      substrate-depent mobility of graphene originates from different carrier density
      but not from the scattering rate.

PMID- 22966662
TI  - Morphology and properties of segregated-network chemically converted graphene
      poly(vinyl chloride) composite.
AB  - The poly(vinyl chloride)-chemically converted graphene (PVC-CCG) composite
      prepared using colloidal blending, filtration and drying, and followed by
      compression molding at 175 degrees C, exhibited an electrical percolation
      threshold as low as 0.4 wt% and an electrical conductivity as high as 46.5 S/m
      corresponding to 4.0 wt% of CCG. The high electrical conductivity of the PVC-CCG
      composite was the result of minimizing the amount of surfactant using various
      methods. For example, the PVC latex was prepared using miniemulsion
      polymerization, and the CCG was synthesized via hydrazine reduction of graphene
      oxide at ambient temperature in order to diminish the irreversible agglomeration
      of CCG sheets during reduction. The morphology of the PVC-CCG composite,
      characterized using scanning electron microscopy in charge contrast mode,
      revealed that the CCG sheets created a segregated network in the PVC matrix.

PMID- 22966663
TI  - Very thin spin-coated silver films via transparent silver ink for surface plasmon
      resonance sensor applications.
AB  - We fabricated very thin silver films with thicknesses of 20 nm, 40 nm, and 60 nm
      on a prism using a spin coating method for surface plasmon resonance (SPR) image
      sensor module applications. An aqueous silver ionic complex solution was spin
      coated and then thermally cured for 10 minutes at 150 degrees C in an oven. The
      spin-coated solid silver films possessed silver crystallinity. The prism modules
      with the 20-nm-, 40-nm- and 60-nm-thick thin silver films were applied to an SPR
      image sensor system. The coefficients of determination for the 20-nm-, 40-nm- and
      60-nm-thick silver films were 0.923, 0.990 and 0.989, respectively when standard
      ethanol solutions with 0.1% intervals in the range of 20.0% to 20.5% were
      applied. The correlation is high-performed and the coefficients of determination
      are as close as 1. The spin coating method of very thin silver films for SPR
      image sensor modules is expected to be a very cost-effective solution because the
      films can be formed at a low temperature in a short period of time without
      requiring a vacuum system.

PMID- 22966664
TI  - Parylene-C-Coated indium tin oxide electrodes for the optical- and electrical
      impedance characterization of cells.
AB  - The demand for the label-free and real-time monitoring of biological cells for
      the diagnosis of diseases and the discovery of new drugs is increasing. The
      electrical-impedance characterization of cells has been used to quantify in real
      time the behaviours of biological cells adhered on the gold or platinum
      microelectrodes. In this article, a parylene-C-coated indium tin oxide (ITO)
      electrode, which has better transparency than the conventional electrodes, and
      high biocompatibility, was investigated for the optical- and electrical-impedance
      characterization of the cell growth. The living cells on the fabricated parylene
      C-coated ITO electrode were observed via phase contrast microscopy, which
      produces high-contrast images of the transparent cells without staining. The
      electrical properties of the cellular parameters were extrapolated through
      fitting analysis with the designed equivalent circuit to the measured impedance
      spectra of the cell-covered electrode. From the experimental results, it was
      proven that the fabricated parylene-C-coated ITO electrode is feasible for the
      optical- and electrical-impedance characterization of cell growth.

PMID- 22966665
TI  - Optical and electronic properties of hydrogenated silicon nanoclusters and
      nitrogen passivated silicon nanoclusters: a density functional theory study.
AB  - Silicon nanoclusters have become significant research interest due to their
      potential application to optoelectronic devices in visible range. We investigate
      the electronic and optical properties of hydrogenated and nitrogen-passivated
      silicon nanoclusters using density functional theory calculations. The energy gap
      between the highest occupied molecular orbital (HOMO) and the lowest unoccupied
      molecular orbital (LUMO) of nanoclusters have varying sizes. They are
      systematically studied using the conventional local density approximation, the
      generalized gradient approximation, and the time-dependent density functional
      theory calculations with hybrid functional. The HOMO-LUMO gap is found to
      decrease monotonically as the size of nanocluster increases. Introducing one and
      two nitrogen passivants to a Si29H36 nanocluster, we find that the HOMO-LUMO gap
      decreases as the number of nitrogen passivants increases. It suggests that multi
      nitrogen passivants may enable light emission in visible range from smaller
      clusters.

PMID- 22966666
TI  - Electrical properties of 10-nm-radius n-type gate all around twin Si nanowire
      field effect transistors.
AB  - The electrical properties of 10-nm-radius n-type gate all around (GAA) twin Si
      nanowire field effect transistors (TSNWFETs) and field effect transistors (FETs)
      without nanowires were investigated to understand their device characteristics.
      The electrical characteristics of the GAA TSNWFETs and FETs with bulk boron
      concentrations of 1 x 10(18) and 1 x 10(16) cm(-3) were simulated by using three
      dimensional technology computer-aided design simulation tools of sentaurus taking
      into account quantum effects. The simulation results showed that the on-current
      level of the TSNWFETs was larger than that of FETs, and the subthreshold swing
      and the drain induced barrier lowing of the TSNWFETs were smaller than those of
      FETs. The current density and conduction band edge profiles in the TSNWFETs
      clarified the dominant current paths. The simulation results showed that the on
      current/off-current ratio increased with increasing bulk boron concentration, and
      the stand-by current level decreased.

PMID- 22966667
TI  - Effect of temperature on optical and electronic properties of InGaP/InGaAIP
      multiple quantum wells.
AB  - The optical and electronic properties in an InGaP/InGaAIP multiple quantum well
      (MQW) grown by using molecular-beam epitaxy utilizing the digital alloy technique
      were investigated through temperature-dependent photoluminescence (PL)
      measurements and numerical calculations. The high-resolution transmission
      electron microscopy images showed that the sample clearly displayed the InGaP
      wells and the InGaAIP barriers and separate confinement heterostructure layers.
      The PL measurements at various temperatures were performed to investigate the
      interband transitions of the InGaP/InGaAIP MQW. The electronic subband energies
      and the wavefunctions in the InGaP/InGaAIP MQW at several temperatures were
      determined by using a finite element method employing the standard 8-band k x p
      Lagrangian. The numerical results for optical interband transition energies from
      the ground state electron subband to the ground state heavy-hole subband of the
      InGaP/InGaAIP MQW at various temperatures were in reasonable agreement with the
      excitonic transition energies observed in the PL measurements.

PMID- 22966668
TI  - Synthesis and photoluminescence properties of Ho3+ doped LaAlO3 nanoparticles.
AB  - Nanosized particles with different Ho3+ concentrations were synthesized in LaAlO3
      lattices using a simple Pechini-type sol-gel method. X-ray diffraction
      measurements were used to investigate the structural composition and the effects
      of holmium dopant concentration on LaAlO3:Ho3+ crystal formation. Field-emission
      scanning-electron microscopy images confirm the formation of approximately
      spherical particles with an average size about 100 nm. The photoluminescence
      results yielded optimal holmium ion concentration in LaAlO3 host matrices was
      about 3% in mol equivalent. The mechanism that are responsible for the
      photoluminescence emission processes discussed with the help of Ho3+-ion Dieke
      energy level diagram. Power dependent slope measurements were performed to
      identify up-conversion photoluminescence process involved in LaAlO3:Ho3+.

PMID- 22966669
TI  - Fabrication of organic shell-covered gold nanospheres with near-infrared
      absorption.
AB  - A simple protocol is developed for the fabrication of stable organic shell
      covered gold nanospheres with near-infrared absorption characteristics. The
      designed strategy mainly concentrates on two steps: (i) the polymerization of
      gold nanoparticles (AuNPs) induced by 1,2-ethanedithiol in water/ethanol; (ii)
      conjugation of the polymerized AuNPs with marocyclic compound for the formation
      of the organic shell. In the first step, the 1,2-ethanedithiol containing two
      thiols towards both ends of the chain enables the successful polymerization of
      AuNPs due to the forceful appetency of thiols to AuNPs. In the second step, the
      polymerized AuNPs are covered by the marocyclic compound attributing to the
      hydrogel-bonding effect between NH and SH. Because of the organic shell, the
      stability and dispersibility of the obtained nanospheres are improved. The
      optical properties of the fabricated gold nanospheres (400 nm average diameter)
      are well investigated by the UV-vis absorption spectroscopy which exhibit intense
      near-infrared absorption at 972 nm in acetone. The strategy developed in this
      study is promising in that excellent stability and dispersibility of gold
      nanospheres can be achieved in a facile and economic way.

PMID- 22966670
TI  - Gate insulator effects on the electrical performance of ZnO thin film transistor
      on a polyethersulphone substrate.
AB  - Low temperature processing for fabrication of transistor backplane is a cost
      effective solution while fabrication on a flexible substrate offers a new
      opportunity in display business. Combination of both merits is evaluated in this
      investigation. In this study, the ZnO thin film transistor on a flexible
      Polyethersulphone (PES) substrate is fabricated using RF magnetron sputtering.
      Since the selection and design of compatible gate insulator is another important
      issue to improve the electrical properties of ZnO TFT, we have evaluated three
      gate insulator candidates; SiO2, SiNx and SiO2/SiNx. The SiO2 passivation on both
      sides of PES substrate prior to the deposition of ZnO layer was effective to
      enhance the mechanical and thermal stability. Among the fabricated devices, ZnO
      TFT employing SiNx/SiO2 stacked gate exhibited the best performance. The device
      parameters of interest are extracted and the on/off current ratio, field effect
      mobility, threshold voltage and subthreshold swing are 10(7), 22 cm2/Vs, 1.7 V
      and 0.4 V/decade, respectively.

PMID- 22966671
TI  - Scanning tunneling microscopy study of nano-structured polyatom-substituted
      H4PW11M1O40 Keggin and H7P2W17M1O62 (M = Nb, Ta) Wells-Dawson heteropolyacid
      catalysts.
AB  - Polyatom-substituted H4PW11M1O40 Keggin and H7P2W17M1O62 (M = Nb, Ta) Wells
      Dawson heteropolyacid (HPA) catalysts were investigated by scanning tunneling
      microscopy (STM) and tunneling spectroscopy to elucidate their redox property and
      oxidation catalysis. STM images clearly showed that HPAs formed nano-structured
      monolayer arrays on graphite surface. In tunneling spectroscopy, HPAs exhibited a
      distinctive current-voltage behavior called negative differential resistance
      (NDR). NDR peak voltage of the HPAs was then correlated with reduction potential
      determined by electrochemical method in solution. NDR peak voltage of the HPAs
      appeared at less negative voltage with increasing reduction potential. Vapor
      phase oxidative dehydrogenation of isobutyraldehyde to methacrolein was also
      carried out as a model reaction to probe oxidation catalysis of the HPAs. NDR
      peak voltage of the HPAs appeared at less negative voltage with increasing yield
      for methacrolein. NDR peak voltage could be utilized as a correlating parameter
      for the reduction potential and as a probe of oxidation catalysis in the
      oxidative dehydrogenation of isobutyraldehyde.

PMID- 22966672
TI  - Characterization of carbon nanotube-cdse hybrid nanomaterials.
AB  - MWNT-CdSe hybrid nanomaterials were prepared with carboxylic acid-treated CdSe
      nanoparticles and amino-functionalized MWNTs. The hybridization of MWNT-CdSe
      nanomaterials was performed by the formation of covalent bond between MWNT and
      CdSe. Their covalent bond lengths were varied with changing the linking spacers.
      Amino-functionalized MWNTs were reacted with CdSe nanoparticles which were
      functionalized with carboxylic acid groups. Their detailed structures were
      characterized by FT-IR, XPS, and small angle X-ray scattering. Through small
      angle X-ray scattering experiments, it was found that the structures of CdSe
      nanoparticles were not regular, and their sizes were broadly distributed in
      solution. The longer amino-functionalized MWNTs were thermally decomposed at
      lower temperature. The photoluminescence (PL) of chemically-linked MWNT-CdSe
      hybrid nanomaterials were weaker than that of CdSe nanoparticles. In addition,
      their PL intensities more weakened on the MWNT-CdSe with the longer spacers.

PMID- 22966673
TI  - Synthesis of sea urchin-like carbon nanotubes on nano-diamond powder.
AB  - Carbon nanotubes (CNTs) have unique atomic structure and properties, such as a
      high aspect ratio and high mechanical, electrical and thermal properties. On the
      other hand, the agglomeration and entanglement of CNTs restrict their
      applications. Sea urchin-like multiwalled carbon nanotubes, which have a small
      aspect ratio, can minimize the problem of dispersion. The high hardness, thermal
      conductivity and chemical inertness of the nano-diamond powder make it suitable
      for a wide range of applications in the mechanical and electronic fields. CNTs
      were synthesized on nano-diamond powder by thermal CVD to fabricate a filler with
      suitable mechanical properties and chemical stability. This paper reports the
      growth of CNTs with a sea urchin-like structure on the surface of the nano
      diamond powder. Nano-diamond powders were dispersed in an attritional milling
      system using zirconia beads in ethanol. After the milling process, 3
      aminopropyltrimethoxysilane (APS) was added as a linker. Silanization was
      performed between the nano-diamond particles and the metal catalyst. Iron
      chloride was used as a catalyst for the fabrication of the CNTs. After drying,
      catalyst-attached nano-diamond powders could be achieved. The growth of the
      carbon nanotubes was carried out by CVD. The CNT morphology was examined by
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      The mean diameter and length of the CNTs were 201 nm and 3.25 microm,
      respectively.

PMID- 22966674
TI  - Superparamagnetism of Cu2Se nanoparticles.
AB  - Cu2Se nanoparticles were synthesized using the standard Schlenk line and glove
      box techniques, with the hot-injection method. The X-ray diffraction (XRD)
      analysis showed that the initial nanoparticles were formed in a stoichiometric
      Cu2Se phase with a cubic structure. When the nanoparticles are exposed to air,
      the diffraction peaks shift to higher angles. This suggests that the
      nanoparticles are changed to a nonstoichiometric Cu2-deltaSe phase with copper
      vacancies. The mean size of the nanoparticles was about 7 nm. The magnetic
      results show that the initial nanoparticles were diamagnetic, and after 1-week
      air exposure, they became paramagnetic. This dramatic change from diamagnetic to
      paramagnetic can be explained by the oxidation of Cu+ into Cu2+ at the
      nanoparticle surface. In addition, the superparamagnetic properties were observed
      to have a blocking temperature of 150 K. The coercive field decreased as the
      temperature approached the blocking temperature, and eventually vanished above
      the blocking temperature.

PMID- 22966675
TI  - Preparation of MoO3/MoS2/TiO2 composites for catalytic degradation of methylene
      blue.
AB  - Metastable hexagonal MoO3 microrods were grown from bulk MoS2 and used as support
      materials for MoS2 and TiO2 nanoparticles. The hybrid composites that consisted
      of MoO3, MoS2, and TiO2 were prepared at a low temperature using the one-step
      synthesis method. The crystallinity and morphology of the MoO3/MoS2/TiO2
      composites that were prepared using HNO3 and titanium tetraisopropoxide were
      compared with those of the MoO3/MoS2 composites that were prepared without
      titanium tetraisopropoxide. Titanium isopropoxide facilitated the formation of
      the MoO3 microrods from the oxidation of the bulk MoS2. The desired
      MoO3/MoS2/TiO2 composites were obtained using 0.5 g of bulk MoS2, 3-4 ml of HNO3,
      and 0.367 ml of titanium tetraisopropoxide. The MoO3/MoS2/TiO2 composites that
      were treated with ultrasonic waves showed rapid degradation of the methylene blue
      solution (2 x 10(-4) M) in the dark and good photocatalytic ability under
      ultraviolet light irradiation. The decomposition of methylene blue depended on
      the composition of the composite.

PMID- 22966676
TI  - A novel aqueous phase synthetic route for CuInSe2 nanocrystals.
AB  - A novel aqueous phase synthetic route for CuInSe2 nanoparticles is presented. In
      our synthesis, the Se precursor used was Na2SeSO3 and CuI, while InCl3 were used
      as precursors for copper and indium, respectively. The reaction was performed in
      water under basic condition in the presence of thioglycolic acid (TGA). TGA has a
      crucial effect on the formation of CIS nanocrystals in aqueous media. With less
      amount of TGA compared to the optimum amount, only amorphous CIS was formed while
      larger amount caused the formation of Cu2-xSe crystals because TGA had a lower
      reactivity of In3+ to Se2- ion. The ratio of reagents used optimized the
      structure, while the composition and properties of the nanomaterials obtained
      were studied applying various techniques such as XRD, SEM, TEM, TG/DSC, and XPS.

PMID- 22966678
TI  - Gigacycle fatigue behavior by ultrasonic nanocrystalline surface modification.
AB  - Nanocrystalline surface layer up to 84 microm in thick is produced on a specimen
      made of Al6061-T6 alloy by means of surface treatment called ultrasonic
      nanocrystalline surface modification (UNSM) technique. The refined grain size is
      produced in the top-layer and it is increased with increasing depth from the top
      surface. Vickers microhardness measurement for each nanocrystalline surface layer
      is performed and measurement results showed that the microhardness is increased
      from 116 HV up to 150 HV, respectively. In this study, fatigue behavior of Al6061
      T6 alloy was studied up to 10(7)-10(9) cycles by using a newly developed
      ultrasonic fatigue testing (UFT) rig. The fatigue results of the UNSM-treated
      Al6061-T6 alloy specimens were compared with those of the untreated specimens.
      The microstructure of the untreated and UNSM-treated specimens was characterized
      by means of scanning electron microscopey (SEM) and transmission electron
      microscopey (TEM).

PMID- 22966677
TI  - Formation of metal and dielectric liners using a solution process for deep trench
      capacitors.
AB  - We demonstrated the feasibility of metal and dielectric liners using a solution
      process for deep trench capacitor application. The deep Si trench via with size
      of 10.3 microm and depth of 71 microm were fabricated by Bosch process in deep
      reactive ion etch (DRIE) system. The aspect ratio was about 7. Then, nano-Ag ink
      and poly(4-vinylphenol) (PVPh) were used to form metal and dielectric liners,
      respectively. The thicknesses of the Ag and PVPh liners were about 144 and 830
      nm, respectively. When the curing temperature of Ag film increased from 120 to
      150 degrees C, the sheet resistance decreased rapidly from 2.47 to 0.72 Omega/sq
      and then slightly decreased to 0.6 Omega/sq with further increasing the curing
      temperature beyond 150 degrees C. The proposed liner formation method using
      solution process is a simple and cost effective process for the high capacity of
      deep trench capacitor.

PMID- 22966679
TI  - Preparation of C60(O)n-ZnO nanocomposite under electric furnace and
      photocatalytic degradation of organic dyes.
AB  - Zinc oxide (ZnO) nanoparticles were synthesized sonochemically by applying
      ultrasonic irradiation to a mixed aqueous-alcoholic solution of zinc nitrate with
      sodium hydroxide at room temperature. The morphology and optical properties of
      the ZnO nanoparticles were examined by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and UV-vis
      spectroscopy. The C60(O)n nanoparticles were synthesized by heating a mixture of
      C60 and 3-chloroperoxybenzoic acid in a benzene solvent under the reflux system.
      The heated C60(O)n-ZnO nanocomposite was synthesized in an electric furnace at
      700 degrees C for two hours. The heated C60(O)n-ZnO nanocomposite was
      characterized by XRD, SEM, and TEM, and examined as a catalyst in the
      photocatalytic degradation of organic dyes by UV-vis spectroscopy. The
      photocatalytic effect of the heated C60(O)n-ZnO nanocomposite was evaluated by a
      comparison with that of unheated C60(O)n nanoparticles, heated C60(O)n
      nanoparticles, and unheated C60(O)n-ZnO in organic dyes, such as methylene blue
      (MB), methyl orange (MO), and rhodamine B (RhB) under ultraviolet light at 365
      nm.

PMID- 22966680
TI  - A convenient alcohol sensor using one-pot nanocomposite entrapping alcohol
      oxidase and magnetic nanoparticles as peroxidase mimetics.
AB  - A colorimetric biosensor for convenient quantification of ethanol and methanol is
      described. The biosensor utilizes a 'one-pot' nanocomposite consisting of Fe3O4
      magnetic nanoparticles (MNPs) and alcohol oxidase (Al Ox) simultaneously
      entrapped in large pore sized mesocellular silica. Al Ox immobilized in the
      silica generates H2O2 in the presence of alcohol in a sample, which subsequently
      activates MNPs in the mesopores of the silica to convert a colorimetric substrate
      into a colored product. Using this strategy, a target alcohol was specifically
      detected through a very convenient colorimetric signal resulting from the
      combined reactions. This strategy enabled successful sensing of ethanol and
      methanol in a linear concentration range from 100 to 500 microM with a detection
      limit as low as 25 microM by employing 2,2'-azino-bis(3-ethylbenzo-thiazoline-6
      sulfonic acid) diammonium salt (ABTS) as a peroxidase substrate. Along with
      excellent reusability via simple magnetic capturing, enhanced operational
      stability was achieved by the nanocomposite system. The present nanocomposite
      would serve as a novel platform for rapid and convenient analysis of alcohol.

PMID- 22966681
TI  - Synthesis of magnetite/amphiphilic polymer composite nanoparticles as potential
      theragnostic agents.
AB  - This study describes the synthesis of magnetite/amphiphilic polymer composite
      nanoparticles that can be potentially used simultaneously for cancer diagnosis
      and therapy. The synthesis method was a one-shot process wherein magnetite
      nanoparticles were mixed with core-crosslinked amphiphilic polymer (CCAP)
      nanoparticles, prepared using a copolymer of a urethane acrylate nonionomer (UAN)
      and a urethane acrylate anionomer (UAA). The CCAP nanoparticles had a hydrophobic
      core and a hydrophilic exterior with both PEG segments and carboxylic acid
      groups, wherein the magnetite nanoparticles were coordinated and stabilized.
      According to DLS data, the ratio of UAN to UAA and the ratio of magnetite to
      polymer are keys to controlling the size and thus, the stability of the composite
      nanoparticles. The magnetic measurement indicated that the composite
      nanoparticles had superparamagnetic properties and high saturation magnetization.
      The preliminary magnetic resonance imaging showed that the particles produced an
      enhanced image even when their concentration was as low as 80 microg/ml.

PMID- 22966682
TI  - Analytic modeling of a depletion-mode cylindrical surrounding-gate nanowire field
      effect transistor.
AB  - A compact model for depletion-mode p-type cylindrical surrounding-gate nanowire
      field-effect transistors (SGNWFETs) is proposed. The SGNWFET model consists of
      two back-to-back Schottky diodes for the metal-semiconductor (MS) contacts and
      the intrinsic SGNWFET. Based on the electrostatic method, the intrinsic SGNWFET
      model was derived from current conduction mechanisms attributed to bulk charges
      through the center neutral region, in addition to accumulation charges through
      the surface accumulation region. The authors' previously developed Schottky diode
      model was used for the M-S contacts. The new model was applied to an advanced
      design system (ADS), whereby the intrinsic part of the SGNWFET and the Schottky
      diode were developed using the Verilog-A language. The results of the simulation
      of the newly developed SGNWFET model reproduced the experiment results
      considerably well.

PMID- 22966683
TI  - Synthesis of Pt doped Bi2O3/RuO2 photocatalysts for hydrogen production from
      water splitting using visible light.
AB  - This study was focused on the preparation of modified bismuth oxide
      photocatalysts, including Ru and Pt doped Bi2O3, using sonochemically assisted
      method to enhance their photocatalytic activity. The crystalline phase
      composition and surface structure of Bi2O3 photocatalysts were examined using
      SEM, XRD, UV-visible spectroscopy, and XPS. Optical characterizations have
      indicated that the Bi2O3 presents the photoabsorption properties shifting from UV
      light region into visible light which is approaching towards the edge of 470 nm.
      According to the experimental results, visible-light-driven photocatalysis for
      water splitting with the addition of 0.3 M Na2SO3 and 0.03 M H2C2O4 as
      sacrificing agents demonstrates that Pt/Bi2O3-RuO2 catalyst could increase the
      amount of hydrogen evolution, which is around 11.6 and 14.5 micromol g(-1) h(-1),
      respectively. Plausible formation mechanisms of modified bismuth oxide and
      reaction mechanisms of photocatalytic water splitting have been proposed.

PMID- 22966685
TI  - Catalytic oxidation of benzene with ozone over nanoporous Mn/MCM-48 catalyst.
AB  - The catalytic oxidation of a representative volatile organic compound, benzene,
      with ozone at a low temperature was investigated. A nanoporous MCM-48 material
      with a high specific surface area was used as the support for the catalytic
      oxidation for the first time. Mn, which has high activity at a low temperature,
      was used as the metal catalyst. To examine the effect of the Mn precursor, MCM-48
      was impregnated with two different Mn precursors: Mn acetate and Mn nitrate. The
      characteristics of the synthesized catalysts were analyzed by Brunauer Emmett
      Teller surface area, X-ray diffraction, X-ray photoelectron spectroscopy, and
      temperature-programmed reduction. MCM-48 impregnated with Mn acetate showed
      higher catalytic activity than MCM-48 impregnated with Mn nitrate. This result
      was attributed to the better dispersion within nanoporous MCM-48 and higher
      oxygen mobility of Mn oxides produced by Mn acetate. The catalytic activity was
      also shown to depend closely on the ozone concentration.

PMID- 22966684
TI  - The effects of substrate and annealing on structural and electrochemical
      properties in LiCoO2 thin films prepared by DC magnetron sputtering.
AB  - LiCoO2 thin films were fabricated by direct current magnetron sputtering method
      on STS304 and Ti substrates. The effects of substrate and annealing on their
      structural and electrochemical properties of LiCoO2 thin film cathode were
      studied. Crystal structures and surface morphologies of the deposited films were
      investigated by X-ray diffraction and field emission scanning electron
      microscopy. The as-deposited films on both substrates have amorphous structure.
      The (104) oriented perfect crystallization was obtained by annealing over 600
      degrees C in STS304 substrate. The LiCoO2 thin film deposited on Ti substrate
      shows the (003) texture after annealing at 700 degrees C. The electrochemical
      properties were investigated by the cyclic voltammetry and charge-discharge
      measurement. The 600 degrees C-annealed LiCoO2 film deposited on STS304 substrate
      exhibits the inithial discharge capacity of 22 uAh/cm2 and the 96% capacity
      retention rate at 50th cycles. The electrochemical measurement on annealed films
      over 600 degrees C was impossible due to the formed TiO2 insulator layer using Ti
      substrate. As a result, it was found that the STS304 substrate seems to be more
      suitable material than the Ti substrate in fabricating LiCoO2 thin film cathode.

PMID- 22966686
TI  - Effect of the initial structure on the electrical property of crystalline silicon
      films deposited on glass by hot-wire chemical vapor deposition.
AB  - Crystalline silicon films on an inexpensive glass substrate are currently
      prepared by depositing an amorphous silicon film and then crystallizing it by
      excimer laser annealing, rapid thermal annealing, or metal-induced
      crystallization because crystalline silicon films cannot be directly deposited on
      glass at a low temperature. It was recently shown that by adding HCI gas in the
      hot-wire chemical vapor deposition (HWCVD) process, the crystalline silicon film
      can be directly deposited on a glass substrate without additional annealing. The
      electrical properties of silicon films prepared using a gas mixture of SiH4 and
      HCl in the HWCVD process could be further improved by controlling the initial
      structure, which was achieved by adjusting the delay time in deposition. The size
      of the silicon particles in the initial structure increased with increasing delay
      time, which increased the mobility and decreased the resistivity of the deposited
      films. The 0 and 5 min delay times produced the silicon particle sizes of
      approximately 10 and approximately 28 nm, respectively, in the initial
      microstructure, which produced the final films, after deposition for 300 sec, of
      resistivities of 0.32 and 0.13 Omega-cm, mobilities of 1.06 and 1.48 cm2 V(-1) S(
      1), and relative densities of 0.87 and 0.92, respectively.

PMID- 22966687
TI  - Temperature dependence of indigo light emission from mesoporous ZnO/porous
      silicon nanocomposites.
AB  - Nanocomposites of mesoporous zinc oxide (ZnO) and porous silicon (PS) were
      prepared through a hydrothermal method. Room-temperature (RT) and temperature
      dependent photoluminescence (PL) were performed to investigate the optical
      properties and temperature dependence of the indigo emission peak from the ZnO/PS
      nanocomposites. An indigo emission peak from the nanocomposites and a red
      emission peak from the PS were observed in the case of the mesoporous ZnO/PS
      nanocomposites. At 10 K, the nanocomposites exhibited four emission peaks at
      3.108, 2.929, 2.730, and 2.248 eV, which correspond to the DX, AX, DX-1LO, and DX
      2LO phonon replicas, respectively. With an increase in temperature from 10 to 275
      K, the curves in the intensities of the emission peaks formed an inverted "S"
      shape while their energies remained nearly constant. At 300 K, however, only the
      AX emission peak was observed; the DX and LO phonon replicas disappeared. The
      intensities of the DX and AX emission peaks exhibited anomalous behaviors.

PMID- 22966688
TI  - Formation of the geometrically controlled carbon coils by manipulating the
      additive gas (SF6) flow rate.
AB  - Carbon coils could be synthesized using C2H2/H2 as source gases and SF6 as an
      incorporated additive gas under the thermal chemical vapor deposition system. The
      nickel catalyst layer deposition and then hydrogen plasma pretreatment were
      performed prior to the carbon coils deposition reaction. The flow rate and the
      injection time of SF6 varied according to the different reaction processes.
      Geometries of carbon coils developed from embryos to nanosized coils with
      increasing SF, flow rate from 5 to 35 sccm under the short SF6 flow injection
      time (5 minutes) condition. The gradual development of carbon coils geometries
      from nanosized to microsized types could be observed with increasing SF6 flow
      rate under the full time (90 minutes) SF6 flow injection condition. The flow rate
      of SF6 for the coil-type geometry formation should be more than or at least equal
      to the flow rate of carbon source gas (C2H2). A longer injection time of SF6 flow
      would increase the size of coils diameters from nanometer to micrometer.

PMID- 22966689
TI  - Influences of Ti film thickness on electrochemical properties of Si/Ti/Cu film
      electrodes.
AB  - Si and Si/Ti films were fabricated on a Cu current collector (substrate) using
      the DC sputtering system. The Ti film as a buffer layer was inserted between the
      Si film and the Cu current collector. Their structural and electrochemical
      properties were investigated with various Ti film thicknesses of 20-90 nm. The Si
      and Ti films deposited on a polycrystalline Cu substrate were amorphous. The
      Si/Ti/Cu film electrode exhibited better electrochemical properties than the
      Si/Cu electrode in terms of capacity, charge-discharge efficiency, and
      cycleability. In the Si/Ti/Cu electrode, the film electrode with a 55 nm Ti film
      thickness showed the best electrochemical properties: 367 microA h/cm2 initial
      capacity, 91% efficiency, and 50% capacity retention after 100 cycles. These good
      electrochemical properties are attributed to the enhanced adhesion between the Si
      and Ti films. Additionally, the modified surface morphology of Si film with a
      cluster structure could withstand the lateral volume change during the charge
      discharge process.

PMID- 22966690
TI  - Synthesis and characterization of conductive core-shell polyacrylonitrile
      polypyrrole nanofibers.
AB  - Nonwoven polyacrylonitrile-polypyrrole (PAN-PPy) core-shell nanofiber mats were
      prepared through the growth of PPy layers on electrospun PAN nanofibers via a two
      step vapor-phase polymerization, i.e., the wet-coating of ferric tosylate (FeTos)
      oxidants on PAN nanofibers followed by exposure to pyrrole monomers in the gas
      phase. Under the conditions ([FeTos] = 10 wt%, reaction time = 15 min,
      temperature = 15 degrees C), the PPy polymerization procedure led to both a
      uniform coating over the PAN surface with an average thickness of 18 nm and cross
      linkages among the nanofibers without a noticeable change in the highly porous
      nanofibrous structures. The oxidant concentration and polymerization time were
      found to be key parameters for achieving a good nanostructured core-shell fiber
      mat. FT-IR, XPS, XRD and conductivity measurements confirmed the synthesis of Tos
      doped PPy with some degree of crystallinity and a high conductivity.

PMID- 22966691
TI  - Rheological and mechanical properties of polypropylene prepared with multi-walled
      carbon nanotube masterbatch.
AB  - In this study, the effects of polypropylene-grafted maleic-anhydride-treated
      multi-walled carbon nanotubes (PP-MWNTs) on the viscoelastic behaviors and
      mechanical properties of a polypropylene-(PP)-based composite system were
      examined. The PP-MWNT/PP composites were prepared via melt mixing with a 3:1
      ratio of PP-g-MA and acid-treated MWNTs at 220 degrees C. The surface
      characteristics of the PP-MWNTs were confirmed via Fourier transform infrared
      (FTIR) spectroscopy and transmission electron microscopy (TEM). The viscoelastic
      behavior and mechanical properties of the PP-MWNT/PP composites were confirmed
      using a rheometer and an ultimate testing machine (UTM). The storage and loss
      moduli increased with increasing PP-MWNT content. The critical intensity stress
      factor (K(IC)) of the PP-MWNT/PP composites at high filler loading was also
      higher than that of the MWNT/PP composites. In conclusion, the viscoelastic
      behavior and mechanical properties of MWNT/PP can be improved by grafting MWNTs
      to PP-g-MA.

PMID- 22966692
TI  - Synthesis and characterization of TiO2/poly(methyl methacrylate) nanocomposites
      via surface thiol-lactam initiated radical polymerization.
AB  - An approach to the surface modification of TiO2 nanoparticles was described based
      on the thiol functionalization of TiO2 followed by thiol-lactam initiated radical
      polymerization (TLIRP) of methyl methacrylate (MMA). FT-IR, XRD and XPS analyses
      confirmed the grafting of the polymer on the TiO2 surface. TGA analysis revealed
      superior thermal stability of PMMA-g-TiO2 compared with PMMA. TEM measurements
      and time-dependent phase monitoring suggested much higher colloidal stability of
      PMMA-g-TiO2 than TiO2 in toluene. The controlled nature of the TLIRP of MMA from
      the surface of TiO2 was determined by GPC analysis.

PMID- 22966693
TI  - Electrospray deposition of silver nanowire films for transparent electrodes.
AB  - Silver nanowire (AgNWs) films were fabricated as transparent electrodes by
      electrostatic spray deposition (ESD) at atmospheric pressure and room
      temperature. The effects of solution concentration, spray flow rate, applied high
      voltage, and annealing temperature were characterized to obtain uniform films.
      AgNWs thin film was produced with ca. 20 Omega/[square] sheet resistance and 83%
      transparency in the visible range. Morphologies, optical and electrical
      properties, and stabilities of the films were investigated in this work. A
      maximum ratio of DC to optical conductivity of 288 was achieved in a 120 nm thick
      AgNW thin film. Chemical stability was evaluated in various solvents and we found
      that solvents had little effect on conductivity.

PMID- 22966694
TI  - Can a repulsive potential in graphene have boundstates in a magnetic field?
AB  - We consider Klein tunneling through a repulsive and cylindrical potential with
      range R and strength V. Recently it was found that, in the strong coupling regime
      R/l < 1, the repulsive potential can have bound states peaked inside the
      potential with tails extending over l mean square root of 2(N+1), where N is
      Landau level (LL) index and f is the magnetic length. The presence of these bound
      states is a consequence of a subtle interplay between Klein tunneling and
      quantization effect of magnetic fields. Because of the presence of these bound
      states the effective coupling between the repulsive potential and an electron can
      be attractive. Here we show that this effect is a consequence of singular
      interaction between the repulsive potential and an electron that cannot be
      captured in perturbative approaches.

PMID- 22966695
TI  - Improved thermal properties of graphene oxide-incorporated poly(methyl
      methacrylate) microspheres.
AB  - Graphene, a single layer of carbon atoms in a two-dimensional lattice, has
      attracted considerable attention owing to its unique physical, chemical and
      mechanical properties. In particular, because of its excellent thermal properties
      such as high thermal conductivity and good thermal stability, graphene has been
      regarded as a one of the promising candidates for the reinforcing fillers on the
      polymer composites field. In this study, we prepared the poly(methyl
      methacrylate) (PMMA)/graphene oxide (GO) nanocomposite by a simple solution
      mixing process, and examined the thermal reinforcing effects of GO on a PMMA
      matrix. Using thermogravimetric analysis, differential scanning calorimeter, and
      thermal conductivity meter, we investigated the effects of GO on the thermal
      properties of PMMA/GO nanocomposites. With 3 wt% of GO loading, the glass
      transition temperature (Tg) of the PMMA/GO nanocomposite were increased by more
      than 7 degrees C and the thermal conductivity of which also improved 1.8 times
      compared to pure PMMA.

PMID- 22966696
TI  - Surface modification to improve hydrophobicity of detonation nanodiamond.
AB  - In this work, surface treatment of nanodiamonds (NDs) produced by a detonation
      technique has been conducted using oleic acid and dodecylamine in order to
      achieve a stable dispersion in oil. From Fourier transform infrared spectroscopy
      (FTIR) analyses, it was found that the NDs have various surface functional groups
      such as -NH2, -COOH, -OH, etc. By inducing covalent bonding between the carboxyl
      group of oleic acid and the amine group of the ND surface with high chemical
      reactivity, NDs were well-dispersed in oil for a lengthy period of time. High
      resolution transmission electron microscopy (HRTEM) images indicate that the
      surface treatment with oleic acid is highly effective in breaking down the
      aggregates of NDs into smaller sized particles. The dispersion stabilities of the
      oils containing as-received NDs and surface treated NDs were compared to each
      other using Turbiscan measurement.

PMID- 22966697
TI  - Preparation and characterization of an electrogenerated chemiluminescence sensor
      by electrochemical grafting of 4-nitrophenyl diazonium salts onto a glass carbon
      electrode.
AB  - An ECL sensor was fabricated by immobilization of a tris(2,2'-bipyridyl)ruthenium
      (II) complex (Ru(bpy)3(2+)) to an amine group-modified GC electrode (NH2-GC
      electrode). Here, the NH2-GC electrode was prepared by electrochemical reduction
      of a nitro group-modified GC electrode in 0.1 M KCl ethanol solution under H2
      gas, which was followed by electrochemical grafting of 4-nitrophenyl diazonium
      salts in 0.1 M NBu4BF4 acetonitrile solution onto the GC electrode. The prepared
      ECL sensor was successfully confirmed via cyclic voltammetry, contact angle,
      scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), and ECL
      spectrometry. The contact angle for the surface of the GC electrode, NO2-GC
      electrode, and NH2-GC electrod was 88.4 degrees, 67.4 degrees, and 52.4 degrees,
      respectively. The stability of the ECL sensor was investigated under continuous
      cyclic potential scanning for 55 cycles and the ECL intensity remained at 55%.
      The prepared ECL electrode can be expected to immobilize enzymes for preparation
      of the ECL biosensor to detect target molecules.

PMID- 22966698
TI  - Silver nanoparticles enhanced luminescence of terbium complex in solution for L
      dopa determination.
AB  - Luminescent properties of a terbium (Tb3+)-L-3, 4-dihydroxyphenylalanine (L-dopa)
      complex by binding to colloidal silver nanoparticles (Ag NPs) have been
      presented. Luminescence intensity of the L-dopa complex was dramatically enhanced
      about 6-7 times by introducing Ag NPs. The Ag NPs concentration on the
      luminescent intensity was regarded as a main factor that balancing between an
      enhancing and a quenching effect of the Ag NPs. It was observed that changing the
      concentration of L-dopa causes the change in luminescence intensity. Under the
      optimized condition, the luminescence intensity of the system was linearly
      related to the concentration of L-dopa. Based on this observation, L-dopa-Tb3+
      complex containing Ag NPs has been applied for the determination of L-dopa in
      pharmaceutical formulation. Linear responses of luminescence intensity were
      observed in the concentration range of 0.25 to 1.5 nM (r = 0.9934) of L-dopa with
      limit of detection 0.042 nM. The performance of the system was tested using 1.0 x
      10(-9) M of L-dopa, yielding a precision of 1.21% RSD for nine replicate
      measurements. The present method has been successfully applied to determine L
      dopa in pharmaceutical samples.

PMID- 22966699
TI  - Micromachining of a bimorph Pb(Zr,Ti)O3 (PZT) cantilever using a micro
      electromechanical systems (MEMS) process for energy harvesting application.
AB  - We designed and fabricated a bimorph Pb(Zr,Ti)O3 (PZT) cantilever with an
      integrated Si proof mass to obtain a low resonant frequency for an energy
      harvesting application. The cantilevers were fabricated on the micro
      electromechanical systems (MEMS) scale. A mode of piezoelectric conversions were
      d31 and d33 mode in cantilever vibration Therefore, we designed and fabricated a
      single cantilever with d31 unimorph, d31 bimorph, d33 unimorph, and d33 bimorph
      modes. Finally, we fabricated a device with beam dimensions of about 5,400 microm
      x 480 microm x 14 microm (< +/- 5%), and an integrated Si proof mass with
      dimensions of about 1,481 microm x 988 microm x 450 microm (< +/- 5%). In order
      to measure the d31 and d33 modes, we fabricated top and bottom electrodes. The
      distance between the top electrodes was 50 microm and the resonant frequency was
      89.4 Hz. The average powers of the d31 unimorph, d31 bimorph, d33 unimorph, and
      d33 bimorph modes were 3.90, 9.60, 21.42, and 22.47 nW at 0.8 g (g = 9.8 m/s2)
      and optimal resistance, respectively.

PMID- 22966700
TI  - Characterization of atmospheric particles in Seoul, Korea using SEM-EDX.
AB  - Atmospheric particles in Seoul, Korea were investigated by scanning electron
      microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX). Particles
      were identified and characterized by their morphology and elemental compositions.
      The morphology of particles was closely coupled with elemental compositions,
      which provided information on sources and transport processes of aerosols. There
      were various types of combustion-derived particles identified such as fly ashes,
      soot, organic matters, tar balls, chars, and sulfur-containing particles. These
      anthropogenic particles mainly have spherical shape with nano- to micro-meter
      size. Char was, however, distinguished by irregular shape with varying size up to
      several micrometers. The sulfur-containing aggregates show a wide range of size,
      shape, and elemental composition. In addition, bioaerosol and mineral dust were
      the most abundant particles from natural sources.

PMID- 22966701
TI  - Plasma treatment effect on dye-sensitized solar cell efficiency of hydrothermal
      processed TiO2 nanorods.
AB  - Atmospheric plasma (AP) treatment was carried out on TiO2 nanorods (NRs) that
      were hydrothermally grown on F-doped SnO2 (FTO)/glass. The effects of AP
      treatment on the surface of the TiO2 NRs were investigated, where the treatment
      involved the use of the reactive gases H2, N2, and O2. The surface energy of AP
      treated TiO2 NRs was about 1.5 times higher than that of untreated TiO2 NRs
      (364.3 mJ/m2). After AP treatment, the increase of the peak area ratios of the
      Ti2O3 and TiO2 peaks in the XPS spectra resulted in a decrease in the number of
      oxygen vacancies in the TiO2 NRs. The efficiency of a dye-sensitized solar cell
      (DSSC) based on the N2-plasma-treated TiO2 NRs, which was approximately 1.11%,
      was about 79% higher than that of a DSSC based on the untreated TiO2 NRs.

PMID- 22966702
TI  - Enhancement of photovoltaic performance in dye-sensitized solar cells with the
      spin-coated TiO2 blocking layer.
AB  - The TiO2 thin film layers were introduced with the spin-coating method between
      FTO electrode and TiO2 photoanode in dye sensitized solar cell (DSSC) to prevent
      electron back migration from the FTO electrode to electrolyte. The DSSC containg
      different thickness of TiO2 thin film (10-30, 40-60 and 120-150 nm) were prepared
      and photovoltaic performances were analysed with /-Vcurves and electrochemical
      impedance spectroscopy. The maximum cell performance was observed in DSSC with 10
      30 nm of TiO2 thin film thickness (11.92 mA/cm2, 0.74 V, 64%, and 5.62%) to
      compare with that of pristine DSSC (11.09 mA/cm2, 0.65 V, 62%, and 4.43%). The
      variation of photoelectric conversion efficiency of the DSSCs with different TiO2
      thin film thickness was discussed with the analysis of crystallographic and
      microstructural properties of TiO2 thin films.

PMID- 22966703
TI  - Preparation and characterization of polyaniline-copper composites by electrical
      explosion of wire.
AB  - Polyaniline-copper composites with a polyacrylic acid (PAA) were synthesized by
      electrical explosion of wire. Polyaniline (PANI) and PAA were put into the
      explosion medium, deionized water (DIW) and ethanol, stirred for 24 hrs and
      sonicated for 2 hrs. These solutions were used as base liquids for explosion
      process to fabricate Cu nanoparticle. Optical absorption in the UV-visible region
      of PANI and PANI/PAA-Cu composites was measured in a range of 200-900 nm. X-ray
      diffraction was used to analyze the phase of the composites. XRD pattern showed
      the PANI was amorphous and copper was polycrystalline. Two phases of Cu and Cu2O
      were formed in aqueous solution while single Cu phase was obtained in ethanol
      solution. Field emission scanning electron microscope was used to observe the
      microstructure of the composites. The synthesized composites were extensively
      characterized by Fourier Transform Infrared (FTIR) spectroscopy and electrical
      measurements.

PMID- 22966704
TI  - Structural analysis of vertically-aligned single crystalline ZnO nanorods grown
      on different seed layers with chemical solution deposition.
AB  - We report the structural properties of the vertically-oriented ZnO nanorods
      fabricated on various ZnO seed layers with chemical solution deposition (CSD)
      technique. The ZnO nanorods were prepared using an aqueous solution with Zinc
      nitrate (Zn(NO3)2 x 6H2O, Aldrich) and hexamethylenetetramine (HMT, Aldrich) in a
      convection oven. A-plane sapphire substrates with a deposited ZnO thin film were
      placed upside down in a quartz holder to avoid any micro-crystalline
      contamination. Especially, our hydro-thermal syntheses are automatically
      processed on precision pump drive systems (Masterflex) to accurately control the
      pH of the aqueous solution. The [002] crystal orientation of the ZnO seed layer
      was observed by the X-ray diffraction pattern. Structural features of ZnO
      nanorods were systematically analyzed by scanning electron microscopy and
      tunneling electron microscopy, together with selective area electron diffraction
      patterns. Experimental observations clearly demonstrated the dependence of the
      growth direction of the ZnO nanorods on the crystal structures of the ZnO seed
      layers.

PMID- 22966705
TI  - Characterization of low-k dielectric SiCOH films deposited with
      decamethylcyclopentasiloxane and cyclohexane.
AB  - Ultra low-k dielectric SiCOH films were deposited with
      decamethylcyclopentasiloxane (DMCPSO, C10H30O5Si5) and cyclohexane (C6H12)
      precursors by plasma-enhanced chemical vapor deposition at the deposition
      temperature between 25 and 200 degrees C and their chemical composition and
      deposition kinetics were investigated in this work. Low dielectric constants of
      1.9-2.4 were obtained due to intrinsic nanoscale pores originating from the
      relatively large ring structure of DMCPSO and to the relatively large fraction of
      carbon contents in cyclohexane. Three different deposition regions were
      identified in the temperature range. Deposition rates increased with temperature
      below 40 degrees C and decreased as temperature increased to 75 degrees C with
      apparent activation energies of 56 kJ/mol x K at < 40 degrees C, -26 kJ/mol x K
      at 40-100 degrees C, respectively. In the temperature region of 40-100 degrees C
      hydrocarbon deposition and decomposition process compete each other and
      decomposition becomes dominant, which results in apparent negative activation
      energy. Deposition rates remain relatively unaffected with further increases of
      temperature above 100 degrees C. FTIR analysis and deposition kinetic analysis
      showed that hydrocarbon deposition is the major factor determining chemical
      composition and deposition rate. The hydrocarbon deposition dominates especially
      at lower temperatures below 40 degrees C and Si-O fraction increases above 40
      degrees C. We believe that dielectric constants of low-k films can be controlled
      by manipulating the fraction of deposited hydrocarbon through temperature
      control.

PMID- 22966706
TI  - Oxidative dehydrogenation of n-butane over vanadium magnesium oxide catalysts
      supported on nano-structured MgO and ZrO2: effect of oxygen capacity of the
      catalyst.
AB  - Vanadium-magnesium oxide catalysts supported on nano-structured MgO and ZrO2
      (Mg3(VO4)2/MgO/ZrO2) were prepared by a wet impregnation method with a variation
      of Mg:Zr ratio (8:1, 4:1, 2:1, and 1:1). For comparison, Mg3(VO4)2/MgO and
      Mg3(VO4)2/ZrO2 catalysts were also prepared by a wet impregnation method. The
      prepared catalysts were applied to the oxidative dehydrogenation of n-butane in a
      continuous flow fixed-bed reactor. Mg3(VO4)2/MgO/ZrO2 (Mg:Zr = 4:1, 2:1, and 1:1)
      and Mg3(VO4)2/ZrO2 catalysts showed a stable catalytic activity during the whole
      reaction time, while Mg3(VO4)2/MgO/ZrO2 (8:1) and Mg3(VO4)2/MgO catalysts
      experienced a severe catalyst deactivation. Deactivation of Mg3(VO4)2/MgO/ZrO2
      (8:1) and Mg3(VO4)2/MgO catalysts was due to their low oxygen mobility. Effect of
      oxygen capacity (the amount of oxygen in the catalyst involved in the reaction)
      of the supported Mg3(V04)2 catalysts on the catalytic performance in the
      oxidative dehydrogenation of n-butane was investigated. Experimental results
      revealed that oxygen capacity of the catalyst was closely related to the
      catalytic activity in the oxidative dehydrogenation of n-butane. A large oxygen
      capacity of the catalyst was favorable for obtaining a high catalytic activity in
      this reaction. Among the catalysts tested, Mg3(VO4)2/MgO/ZrO2 (4:1) catalyst with
      the largest oxygen capacity showed the best catalytic performance.

PMID- 22966707
TI  - Hydrogenation of CO to methane over mesoporous nickel-iron-alumina xerogel nano
      catalysts.
AB  - Mesoporous nickel-iron-alumina xerogel ((40-x)Ni(x)FeAX) nano-catalysts with
      different iron content (x = 0, 2.5, 5, 7.5, and 10) were prepared by a single
      step sol-gel method for use in the methane production from carbon monoxide and
      hydrogen. The effect of iron content on the catalytic performance of (40
      x)Ni(x)FeAX catalysts was investigated. In the methanation reaction, yield for
      CH4 decreased in the order of 35Ni5FeAX > 32.5Ni7.5FeAX > 30Ni10FeAX >
      37.5Ni2.5FeAX > 40Ni0FeAX. This indicated that optimal iron content of mesoporous
      nickel-iron-alumina xerogel nano-catalyst was required for maximum production of
      CH4 in the methanation reaction. Experimental results revealed that optimal CO
      dissociation energy and large H2 adsorption ability of the catalyst were
      favorable for methane production. Among the catalysts tested, 35Ni5FeAX catalyst,
      which retained the most optimal CO dissociation energy and the largest H2
      adsorption ability, exhibited the best catalytic performance in terms of
      conversion of CO and yield for CH4 in the methanation reaction. CO dissociation
      energy and H2 adsorption ability of the catalyst played a key role in determining
      the catalytic performance of (40-x)Ni(x)FeAX in the methanation reaction.

PMID- 22966708
TI  - Nano-sized Mn-doped activated carbon aerogel as electrode material for
      electrochemical capacitor: effect of activation conditions.
AB  - Carbon aerogel (CA) was prepared by a sol-gel polymerization of resorcinol and
      formaldehyde, and a series of activated carbon aerogels (ACA-KOH-X, X = 0, 0.3,
      0.7, 1, and 2) were then prepared by a chemical activation using different amount
      of potassium hydroxide (X represented weight ratio of KOH with respect to CA).
      Specific capacitances of activated carbon aerogels were measured by cyclic
      voltammetry and galvanostatic charge/discharge methods in 6 M KOH electrolyte.
      Among the samples prepared, ACA-KOH-0.7 showed the highest specific capacitance
      (149 F/g). In order to combine excellent electrochemical performance of activated
      carbon aerogel with pseudocapacitive property of manganese oxide, 7 wt% Mn was
      doped on activated carbon aerogel (Mn/ACA-KOH-0.7) by an incipient wetness
      impregnation method. For comparison, 7 wt% Mn was also impregnated on carbon
      aerogel (Mn/ACA-KOH-0) by the same method. It was revealed that 7 wt% Mn-doped
      activated carbon aerogel (Mn/ACA-KOH-0.7) showed higher specific capacitance than
      7 wt% Mn-doped carbon aerogel (Mn/ACA-KOH-0) (178 F/g vs. 98 F/g). The enhanced
      capacitance of Mn/ACA-KOH-0.7 was attributed to the outstanding electric
      properties of activated carbon aerogel as well as the faradaic redox reactions of
      manganese oxide.

PMID- 22966709
TI  - Fabrication and photovoltaic properties of heterostructured TiO2 nanowires.
AB  - One-dimensional heterostructured TiO2 nanowires were successfully fabricated by
      an electrospinning technique and modified by hydrolysis. We investigated their
      structure, morphology, chemical composition, and optical properties by using the
      X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and UV-vis
      spectroscopy. In the case of the photovoltaic performance, the short-circuit
      current density and cell efficiency of the DSSCs employing single TiO2 nanowires
      and heterostructured TiO2 nanowires improve from 6.90 to 11.38 mA/cm2 and from
      2.56 to 4.29%, respectively. The results show that the photoconversion efficiency
      of the heterostructured TiO2 nanowires could be improved by more than
      approximately 67% compared to that of the single TiO2 nanowires because of the
      enhanced specific surface area that facilitates dye adsorption.

PMID- 22966710
TI  - Sr0.95Zn0.05Se:Eu2+ and CdSe/ZnS nanocrystals hybrid phosphors for enhancing
      color rendering index of white light emitting diode.
AB  - In this study, the yellow emitting cubic structure of Sr0.95Zn0.05Se:Eu2+
      phosphors were prepared by high temperature solid state reaction. The
      Sr0.95Zn0.05Se:Eu2+ phosphors exhibited strong excitation intensity under 400-460
      nm region, and broad band emission appeared at around 545-600 nm due to the d-f
      transition of Eu2+. To enhance the red emission, HDA/TOP/TOPO capped CdSe/ZnS NCs
      were synthesized via fast nucleation and slow growth method. The narrow emission
      peak was located at 615 nm with 69% of high quantum yield. Bright white emission
      was generated by combining a 460 nm InGaN LED chip with CdSe/ZnS NCs and
      Sr0.95Zn0.05Se:Eu2+ hybrid phosphors. The fabricated white LEDs showed warm white
      light with acceptable CIE chromaticity coordinate variation from (0.343, 0.255)
      at 20 mA to (0.335, 0.250) at 50 mA. The addition of CdSe/ZnS NCs contributed to
      the extension of white light spectrum by supplement of the red region. The color
      rendering index was largely enhanced from 41.7 to 79.7 compared to the
      Sr0.95Zn0.05Se:Eu2+ based phosphors white LED.

PMID- 22966711
TI  - Preparation of highly dispersed tungsten oxide on MCM-41 via atomic layer
      deposition and its application to butanol dehydration.
AB  - Highly dispersed tungsten oxide on MCM-41 was synthesized using a novel atomic
      layer deposition (ALD) method. BET, XRD, XPS, NH3-TPD, and pyridine-IR were used
      to study the physicochemical properties of the supported tungsten oxides. In this
      study, the maximum loading of tungsten oxide on MCM-41 that could be prepared
      using the modified ALD method was 27.0 wt%. It was confirmed that the textural
      properties of the mesoporous silica were maintained after tungsten oxide loading.
      The NH3-TPD and Py-IR results indicated that weak acid sites, mainly Lewis acid
      sites, were produced over the WO3/MCM-41 samples. Moreover, 2-butanol dehydration
      was performed to demonstrate the potential advantages of the WO3/MCM-41
      catalysts. The WO3/MCM-41 catalyst with 27.0 wt% tungsten oxide loading showed
      the highest activity in the dehydration of 2-butanol, which was attributed to the
      highest overall number of acid sites among the WO3/MCM-41 catalysts. The highly
      dispersed tungsten oxide on MCM-41 prepared via ALD can be an effective catalyst
      for producing butenes through 2-butanol dehydration.

PMID- 22966712
TI  - Catalytic effects of ZnO nanorods grown by sonochemical decomposition of zinc
      acetate dihydrate.
AB  - In this study, we prepared ZnO nanorods by a sonochemical method using a zinc
      acetate dihydrate as a new precursor. Well-aligned high-quality ZnO nanorods were
      synthesized on FTO glass by the sonochemical decomposition of zinc acetate
      dihydrate using a ZnO thin-film as the catalytic layer. The ZnO thin-films were
      deposited on the FTO glass by a sputtering method. To investigate their catalytic
      effects on the ZnO nanorods, catalytic ZnO thin-films of 20 nm, 40 nm, and 60 nm
      thickness were prepared by adjusting the sputtering time. The ZnO nanorods grown
      on catalytic layers with different thicknesses were characterized by SEM, XRD,
      and PL. The ZnO nanorods grown on the catalytic layer of 40 nm thickness show the
      best crystal and spatial orientation and as a result display the best optical
      properties. It was found that a catalytic ZnO thin-film of 40 nm in thickness
      yields well-aligned high-quality ZnO nanorods, due to its small surface roughness
      and structural strain.

PMID- 22966713
TI  - Magnetic properties of hydrogen-included TiZrNiPd quasicrystals.
AB  - Quasicrystals prepared by rapid quenching of Pd-added TiZrNi ingots were
      hydrogenated, and effects of hydrogen for magnetic properties were compared with
      the unhydrogenated ones under magnetic fields from -10000 to 10000 Oe. The
      magnetization values obtained from vibrating sample magnetometer (VSM) were
      analyzed with the combination of powder X-ray diffraction (XRD) data. While its
      contribution is larger than that of Pd, hydrogen decreases the magnetic moments
      of both Pd-doped and undoped quasicrystals. As increasing the amount of absorbed
      hydrogen which is represented by H/M (hydrogen to host metal atom ratio) values
      from 0 to 1.19, the magnetization values of Ti53Zr27Ni20 quasicrystals measured
      at 10000 Oe significantly decreased from 0.301 to 0.212 emu/g. A careful analysis
      of XRD data demonstrated that the reduced interactions of magnetic dipole moments
      between Ni atoms, as the product of the expansion of the quasilattice constants
      after hydrogenation, are responsible for the decreased magnetization values in
      hydrogenated TiZrNiPd quasicrystal samples.

PMID- 22966714
TI  - Fatigue characteristics of SAE52100 steel via ultrasonic nanocrystal surface
      modification technology.
AB  - Ultrasonic nanocrystal surface modification (UNSM) technology is a novel surface
      modification technology that can improve the mechanical and tribological
      properties of interacting surfaces in relative motion. UNSM treatment was
      utilized to improve the wear resistance fatigue strength of slim bearing rings
      made of SAE52100 bearing steel without damaging the raceway surfaces. In this
      study, wear and fatigue results that were subjected to different impact loads of
      the UNSM treatment were investigated and compared with those of the untreated
      specimen. The microhardness of the UNSM-treated specimens increased by about 20%,
      higher than that of the untreated specimens. The X-ray diffraction analysis
      showed that a compressive residual stress of more than 1,000 MPa was induced
      after the UNSM treatment. Also, electron backscatter diffraction analysis was
      used to study the surface structure and nanograin refinement. The results showed
      that the rolling contact fatigue life and the rotary bending fatigue strength of
      the UNSM-treated specimens increased by about 80% and 31%, respectively, compared
      to those of the untreated specimen. These results might be attributed to the
      increased microhardness, the induced compressive residual stress, and the
      nanocrystal structure modification after the UNSM treatment. In addition, the
      fracture surface analysis showed that the fish eye crack initiation phenomenon
      was observed after the UNSM treatment.

PMID- 22966715
TI  - The oxides growth during high-temperature oxidation of Si1-xGe(x) nanowires.
AB  - Concerning the oxidation behavior of Si1-xGe(x) (x = 0.15, 0.3) nanowires at high
      temperature, Si1-xGe(x) nanowires were thermally oxidized for various lengths of
      time compared with Si nanowires, Si and Si1-xGe(x) thin films. The structural and
      compositional properties of the oxidized nanowires were characterized using
      several transmission electron microscopy (TEM) techniques including energy
      dispersive X-ray spectroscopy (EDS), which confirm that the oxidation rates of
      Si1-xGe(x) and Si (silicon) nanowires were saturated with increasing oxidation
      time due to retarding behavior, while the oxidation rate of Si1-xGe(x) nanowires
      were faster than that of Si nanowires. In addition, the differences in Ge
      (germanium) content and stress distribution contribute to the observed
      differences in oxidation behavior.

PMID- 22966716
TI  - Effect of gas phase composition cycling on/off modulation numbers of C2H2/SF6
      flows on the formation of geometrically controlled carbon coils.
AB  - Carbon coils can be synthesized using C2H2/H2 as source gases and SF6 as an
      incorporated additive gas under a thermal chemical vapor deposition system. In
      this study, nickel catalyst layer deposition and then hydrogen plasma
      pretreatment were performed prior to the carbon coils deposition reaction. To
      obtain geometrically controlled carbon coils, source gases and SF6 were
      manipulated as the cycling on/off modulation numbers of C2H2/SF6 flows. The
      cycling numbers were varied according to the different reaction processes. The
      increased cycling numbers could develop the wave-like nano-sized carbon coils. By
      further increasing the cycling numbers, however, the nanostructured carbon coils
      seemed to deteriorate. As a result, the maximum formation of geometrically
      controlled carbon coils was achieved by adjusting the cycling numbers. The
      enhanced etching capability of the fluorine-related species in SF6 additive gas
      was considered for the main objective of controlling the geometry of carbon
      coils.

PMID- 22966717
TI  - Mass sensitivity calculation of the protein layer using love wave SAW biosensor.
AB  - Love waves, a variety of surface acoustic waves (SAWs), can be used to detect
      very small biological surface interactions and so have a wide range of potential
      applications. To demonstrate the practicality of a Love wave SAW biosensor, we
      fabricated a 155-MHz Love wave SAW biosensor and compared it with a commercial
      surface Plasmon resonance (SPR) using glycerol-water solution with known
      densities and viscosities to calibrate the response signals of the biosensors.
      And the mass per unit area of anti-mouse IgG bound with protein G onto the
      sensitive layer of the biosensor was calculated on the basis of the calibration
      result. The sensitivity of the Love wave SAW biosensor was the same as or greater
      than that of the SPR biosensor. Furthermore, the Love wave SAW biosensor was
      capable of measuring a much wider range of viscosities than the SPR biosensor.
      Although the operating principle of the Love wave SAW biosensor is completely
      different from that of the SPR biosensor, the subtle changes in the viscoelastic
      properties of the biological layer that accompany biological binding reactions on
      the sensitive layer can be monitored and measured in the same ways as with the
      SPR biosensor.

PMID- 22966718
TI  - Density functional calculations on the mechanical properties of nitrogen or
      oxygen doped crystalline Ge2Sb2Te5.
AB  - The mechanical properties of pure and doped crystalline Ge2Sb2Te5 were
      investigated by using density functional calculations. Nitrogen or oxygen was
      added at either the interstitial or substitutional sites of cubic Ge2Sb2Te5. The
      lattice parameter, elastic stiffness and related moduli were investigated from
      the viewpoint of the doping concentration, dopant species, dopant states and film
      direction. The effect of the doping concentration was more dominant than those of
      the dopant species and their states on the non-directionality properties, such as
      the bulk modulus and lattice parameter. It turned out that Ge2Sb2Te5 became
      slightly more rigid as the doping concentration of nitrogen or oxygen increased.
      On the other hand, the effect of the film direction on the directional
      properties, such as the biaxial modulus of the Ge2Sb2Te5 film, was found to be
      more predominant than that of doping. The biaxial modulus of the (001) oriented
      film was calculated to be much higher than those of the other films, indicating
      that the (001) film is the most vulnerable to thermal stress.

PMID- 22966719
TI  - Characterization of polyacrylonitrile based carbon nanofiber mats via electron
      beam processing.
AB  - The aim of this study was to evaluate the ability of electron beam irradiation to
      drive stabilization reactions within PAN nanofiber mats to obtain carbon
      nanofiber mats. PAN nanofiber mats with fiber diameters of 300-400 nm were
      prepared via an electrospinning method. Electrospun PAN nanofiber mats were
      stabilized by electron beam irradiation with various doses up to 5,000 kGy. Using
      the irradiation-stabilized PAN nanofiber mats, carbon nanofibers were obtained by
      pyrolysis in a tube furnace for 1 h at 1,000 degrees C under an N2 atmosphere. FT
      IR analysis indicated that the transformation of C[triple bond]N groups to C==N
      groups was accelerated by electron beam stabilization. The thermal behavior of
      the PAN nanofiber mats was studied using DSC and TGA. DSC thermograms showed that
      the peak temperatures of the exothermic reactions were found to decrease with
      increasing electron beam irradiation doses. Irradiation-stabilized PAN nanofiber
      mats were not observed to dramatically decrease in weight between 290 degrees C
      and 320 degrees C, an observation presumed to be related to cyclization. The char
      yields of PAN were found to increase with increasing irradiation doses.

PMID- 22966720
TI  - Enhanced luminescence of lanthanide complexes by silver nanoparticles for
      ciprofloxacin determination.
AB  - We present the enhancement of luminescence of europium complex, Eu(3+)
      ciprofloxacin (CIP), in the presence of silver nanoparticles (Ag NPs) for the CIP
      determination. The increment of the luminescence intensity of the Eu(3+)-CIP
      complex with Ag NPs was obtained due to the transfer of resonance energy to the
      fluorophores through the interaction of the excited-state fluorophores and
      surface plasmon electron in the metal nano surface. The luminescence intensity of
      Eu3+ was enhanced by complexation with CIP at 614 nm after excitation at 373 nm
      corresponding to the 5D0-7F2 transitions of Eu3+ ion. Based on the above
      phenomenon, a sensitive and rapid spectrofluorimetric method has been developed
      for the CIP determination. Linearity of the calibration curve was obtained in the
      range of 2.0 x 10(-10)-1.0 x 10(-8) g mL(-1) with correlation coefficient of
      0.9992. The limit of detection of CIP was found to be 1.9 x 10(-11) g mL(-1) with
      the relative standard deviation (RSD) of 1.19% for 5 replicate measurements of
      5.0 x 10(-7) g mL(-1) of CIP. The present method has been successfully applied
      for CIP determination in pharmaceutical and biological samples.

PMID- 22966721
TI  - Comparative physicochemical characterization and bioavailability of nano
      liposomes formed by mixing lipids at different ratios.
AB  - Liposomes are small lipid vesicles that mimic biological membranes and have been
      spotlighted in the clinical field due to their ability to enclose a biologically
      active substance of any structure and to release it into the host's body. This
      study compares the physicochemical properties and biological activity of nano
      liposomes with different compositions to determine the most effective formulation
      for further in vivo application. Nano-scale liposomes composed of different
      ratios of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), dihexadecyl
      phosphate (DCP), and cholesterol (Chol): DMPE, DMPE/DCP, DMPE/Chol, and
      DMPE/DCP/Chol were produced. The thermal phase transition was assessed via
      differential scanning calorimetry (DSC); the particle size, via dynamic light
      scattering (DLS); the colloidal stability, via the zeta potential; the direct
      morphological characterization, via transmission electron microscopy (TEM); and
      the protein encapsulation efficiency. The bioavailability was also investigated
      with respect to the immunological responses via porcine interferon gamma (IFN
      gamma) enzyme-linked immunospot (ELISPOT) assay in peripheral blood mononuclear
      cells (PBMC) of immunocompetent pigs. All the liposomes can be expected to be
      stable in an in vivo physiological temperature, and the liposomes that were
      prepared from DMPE/DCP showed the best efficiency in the in vitro model that
      mimicked the release of a bioactive substance in vivo. In the result of DLS and
      the zeta potential for the investigation of the colloidal stability in the
      system, DMPE/DCP/Chol appeared better than the other formulations. The porcine
      IFN-gamma ELISPOT assay results postulated that DMPE/DCP most potently induced
      the IFN-gamma secretion by PBMC, followed by DMPE/DCP/Chol and DMPE alone, in
      that order.

PMID- 22966722
TI  - Bacterial cellulose nanocrystals-embedded silk nanofibers.
AB  - Nanofibrous Bacterial cellulose nanocrystals (BCNs)-embedded silk fibroin were
      successfully fabricated using electrospinning. The morphology, structure and
      mechanical properties of the silk fibroin nanofibers were investigated at various
      BCNs concentrations from 0 to 7 wt%. SEM, TEM and XRD analyses were conducted to
      confirm the incorporation of the BCNs in the electrospun silk fibroin nanofibers.
      The average diameter of the silk fibroin/BCNs nanofibers increased from 230 to
      430 nm according to the increasing of the BCNs ratio due to the rising solute
      content. The FT-IR spectra confirmed the conformational transition of the silk
      fibroin, from a random coil to a beta-sheet structure, which shows the enhanced
      mechanical properties of silk fibroin based nanofibers even with small amounts of
      the BCNs. Moreover, it was observed that the Young's modulus of the silk
      fibroin/BCNs nanofibers unexpectedly increased with the formation of BCNs with a
      percolation structure at a concentration between 3 and 5 wt%.

PMID- 22966723
TI  - [Primary ciliary dyskinesia: clinical and genetic aspects].
AB  - Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease,
      characterized by ciliary disfunction and impaired mucociliary clearance,
      resulting in a range of clinical manifestations such as chronic bronchitis,
      bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum
      inversus in almost 40-50% of cases and male infertility. The triad situs viscerum
      inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now
      little is known about genetic, diagnostic and therapeutic aspects of primary
      motile ciliary diseases in children: for this reason, diagnosis is generally
      delayed and almost all treatments for PCD are not based on randomized studies but
      extrapolated from cystic fibrosis guidelines. The aim of this review is to
      propose to pediatricians a summary of current clinical and diagnostic evidence to
      obtain better knoledwge of this condition. The earlier diagnosis and the right
      treatment are both crucial to improve the prognosis of PCD.

PMID- 22966724
TI  - Septic arthritis in children.
AB  - Osteoarticular infections are a form of diagnostic and therapeutic emergency in
      infants and children, even if relatively rare. Despite decades of experience with
      different protocols, and multiple clinical trials, today it is still difficult to
      determine what kind of antibiotics is really effective, what kind of associations
      are required, which is the optimal time range of a treatment, when and on which
      subjects to base the transition from a parenteral treatment to an oral one.
      Current philosophy aims more and more at reducing hospitalization and costs, and
      wants to decrease the discomfort in the family. The purpose of these guidelines
      is to promote a reasoned clinical and therapeutic approach, in a context of
      diagnostic probabilities that offer the best chance of success in reducing
      hospitalization with a rapid transition to an oral treatment, and then
      outpatient, and thus educing totally the processing time.

PMID- 22966725
TI  - [Long term efficacy of insulin pump therapy in preschool children with diabetes].

PMID- 22966726
TI  - Cardiocirculatory intraoperative assessment during single-shot caudal anaesthesia
      in children: comparison between levobupivacaine and ropivacaine.
AB  - BACKGROUND: Caudal block with levobupivacaine or ropivacaine is the most commonly
      used regional anaesthesia in children. METHODS: The aim of study was to compare
      the cardiocirculatory profile induced in two matched groups of young patients,
      submitted to caudal anaesthesia with levobupivacaine or ropivacaine for an
      elective subumbilical surgery. Sixty children were enrolled: thirty received
      levopubivacaine 0.25% and thirty ropivacaine 0.2%. Intraoperative heart rate
      (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) were
      monitored at following times: Ta0 (after anaesthesia induction), Tal (after
      caudal anaesthesia), Ta2 (five minutes later), Ta3 (ten minutes later), Ts1 (at
      surgical incision), Ts2, Ts3, Ts4, Ts5 (every 10 minutes during surgery), Taw (at
      the awakening). RESULTS: In both groups the cardiocirculatory trend remained
      within normal ranges at all times considered, demonstrating the safety of the
      method with both drugs. Both groups showed a similar trend at the different
      monitoring times: low decrease in HR, SBP and DBP after caudal block, slight
      increase in parameters after skin incision, slight decrease during surgery,
      increase at awakening. Regarding SBP and DBP, the levobupivacaine group children
      generally showed higher levels compared to the ropivacaine group, especially for
      DBP. CONCLUSIONS: Paediatric caudal anaesthesia is an effective method with an
      very infrequent complication rate. Possible hypotheses for differing haemodynamic
      behaviour could include a stronger vasoconstriction reflex of innervated areas
      during caudal anaesthesia with levobupivacaine and a lower levobupivacaine
      induced block of the sympathetic fibers, related to different pharmacokinetic
      profile of low concentrations of the local anaesthetics used in paediatric
      epidural space.

PMID- 22966727
TI  - [Ovarian cyst in a newborn: a case report].
AB  - The presence of ovarian cysts in the newborn is often a sign of an abnormal
      exacerbation of the physiologic process. In our case a large cyst caused symptoms
      related to gastroesophageal reflux: vomiting, poor weight gain, and respiratory
      disorders. Ultrasound examination enabled a correct diagnosis.

PMID- 22966728
TI  - Acute splenic torsion in children: which is the best treatment? A case report.
AB  - Wandering spleen is a clinical entity which rarely affects children and
      adolescents. This condition can be asymptomatic or responsible of chronic pain,
      but it appears as a surgical emergency when an acute twisting occurs. The risk of
      post-splenectomy sepsis in the pediatric population suggests a conservative
      approach whenever possible, and also in case of acute torsion, most authors
      prefer to preserve the spleen and perform a splenopexy. The Authors describe a
      case of a child with acute splenic torsion, in whom a conservative surgical
      approach was initially adopted. The conservative option has to be balanced with
      the risk of prolonged thrombocytopenia, multiple transfusions and a possible
      second procedure to remove the spleen.

PMID- 22966729
TI  - Dental enamel, fluorosis and amoxicillin.
AB  - INTRODUCTION: Amoxicillin is one of the most used antibiotics among pediatric
      patients for the treatment of upper respiratory tract infections and specially
      for acute otitis media (AOM), a common diseases of infants and childhood. It has
      been speculated that the use of amoxicillin during early childhood could be
      associated with dental enamel fluorosis, also described in literature with the
      term Molar Incisor Hypomineralization (MIH), because they are generally situated
      in one or more 1st permanent molars and less frequently in the incisors. The
      effect ofAmoxicillin seems to be independent of other risk factors such as
      fluoride intake, prematurity, hypoxia, hypocalcaemia, exposure to dioxins,
      chikenpox, otitis media, high fever and could have a significant impact on oral
      health for the wide use of this drug in that period of life. OBJECTIVE: The aim
      of this work was to review the current literature about the association between
      amoxicillin and fluorosis. METHODS AND RESULTS: A literature survey was done by
      applying the Medline database (Entrez PubMed); the Cochrane Library database of
      the Cochrane Collaboration (CENTRAL). The databases were searched using the fol
      lowing strategy and keywords: amoxicillin* AND (dental fluorosis* OR dental
      enamel*) and MIH*. After selecting the studies, only three relevant articles
      published between 1966 and 2011 were included in the review. CONCLUSION: The
      presence of several methodological issues does not allow to draw any evidence
      based conclusions. No evidence of association was detected, therefore, there is a
      need of further well-designed studies to assess the scientific evidence of the
      relationship between amoxicillin and fluorosis and to restrict the prescription
      of this drug for recurrent upper respiratory tract infections especially acute
      otitis media (AOM) during the first two years of life. When it is possible can be
      opportune to use an alternative antibiotic treatment.

PMID- 22966730
TI  - Public health ethical perspectives on the values of the European Commission's
      White Paper "Together for Health".
AB  - BACKGROUND: In 2007 the European Commission issued the White Paper: "Together for
      Health". Considered the EU Health Strategy for the years 2008-2013, it offers the
      cornerstones for setting priorities in EU health actions. OBJECTIVES: The public
      health framework offered in this strategy is explicitly built on shared values-
      including the overarching values of universality, access to good quality care,
      equity and solidarity that reacted to certain health care challenges within the
      EU. This article analyses the Health Strategy via its ethical scope and considers
      implications for future health policy making. METHODS: The Health Strategy and
      related documents are scrutinised to explore how the mentioned values are defined
      and enfolded. Additionally, scientific databases are searched for critical
      discussions of the value base of the Health Strategy. The results are discussed
      and reasoned from a public health ethical perspective. RESULTS: The Health
      Strategy is barely documented and discussed in the scientific literature.
      Furthermore, no attention was given to the value base of the Health Strategy. Our
      analysis shows that the mentioned values are particularly focussed on health care
      in general rather than on public health in particular. Besides this, the given
      values of the Health Strategy are redundant. CONCLUSIONS: An additional
      consideration of consequentialist public health ethics values would normatively
      strengthen a population-based health approach of EU health policy making.

PMID- 22966731
TI  - Dramatic decline of ischaemic heart disease mortality in post communist central
      Europe: recovery from totality.
AB  - After 1970 the preexisting gap in population health between democratic Europe and
      communist countries became even more prominent. While in the democratic Europe
      there was a progressive rise in life expectancy associated with the decline in
      ischaemic heart disease (IHD), the trend on the other side of the iron curtain
      was exactly reverse. After the fall of communism in 1989 population health in the
      post-communist central Europe (CE) rapidly signalled a favourable recovery. This
      biphasic trend in post-communist countries is very remarkable. Most remarkably
      the decline in IHD mortality started soon after the demise of totality, even
      before the modernization of health care (new more effective medications and
      diagnostic technology), public campaign against smoking and improved supply of
      protective nutrients got chance to attain an important role. The decades-long
      psychosocial depression of communism was rapidly replaced with a promise of a
      better future. It is generally accepted that psychosocial factors are powerfool
      tools in the pathogenesis of IHD.

PMID- 22966732
TI  - Validation of a Greek version of PSS-14; a global measure of perceived stress.
AB  - AIM: To evaluate validity of the Greek version of a global measure of perceived
      stress PSS-14 (Perceived Stress Scale - 14 item). MATERIALS AND METHODS: The
      original PSS-14 (theoretical range 0-56) was translated into Greek and then back
      translated. One hundred men and women (39 +/- 10 years old, 40 men) participated
      in the validation process. Firstly, participants completed the Greek PSS-14 and,
      then they were interviewed by a psychologist specializing in stress management.
      Cronbach's alpha (a) evaluated internal consistency of the measurement, whereas
      Kendall's tau-b and Bland & Altman methods assessed consistency with the clinical
      evaluation. Exploratory and Confirmatory Factor analyses were conducted to reveal
      hidden factors within the data and to confirm the two-dimensional character of
      the scale. RESULTS: Mean (SD) PSS-14 score was 25(7.9). Strong internal
      consistency (Cronbach's alpha = 0.847) as well as moderate-to-good concordance
      between clinical assessment and PSS-14 (Kendall's tau-b = 0.43, p < 0.01) were
      observed. Two factors were extracted. Factor one explained 34.7% of variability
      and was heavily laden by positive items, and factor two that explained 10.6% of
      the variability by negative items. Confirmatory factor analysis revealed that the
      model with 2 factors had chi-square equal to 241.23 (p < 0.001), absolute fix
      indexes were good (i.e. GFI = 0.733, AGFI = 0.529), and incremental fix indexes
      were also adequate (i.e. NFI = 0.89 and CFI = 0.92). CONCLUSION: The developed
      Greek version of PSS-14 seems to be a valid instrument for the assessment of
      perceived stress in the Greek adult population living in urban areas; a finding
      that supports its local use in research settings as an evaluation tool measuring
      perceived stress, mainly as a risk factor but without diagnostic properties.

PMID- 22966733
TI  - Volunteering and mutual aid in health and social care in the Czech Republic as an
      example of active citizenship.
AB  - This article informs about recent research findings on voluntary and mutual aid
      in the Czech Republic with a special attention paid to formal volunteering in
      health and social care. The data suggest that public involvement is comparable to
      middle-frequency experienced in European countries. In this respect, volunteering
      is higher in the Czech Republic than in other former Eastern European countries
      and is an evidence of a successful and rapid restoration of the civic sector. New
      patterns of volunteering featured by planning, coordination, and contracting have
      spread out being strongly supported by national and EU policy measures.
      Managerial patterns of volunteering are dominating in health and social care
      institutions. Volunteering in health and social care is firmly motivated by
      emotional altruism; however, reciprocal (instrumental) and normative motivations
      are also present, though to a lesser extent compared to other sectors of
      volunteer activities. In the managerial pattern of volunteering altruism is
      balanced with personal gains and benefits for those who volunteer. Volunteering
      is deeply embedded in a civic, humanitarian paradigm instead of a religious faith
      and duty.

PMID- 22966734
TI  - Pattern of road traffic injuries in Lublin County, Poland.
AB  - BACKGROUND: Road traffic injury patients admitted to 35 hospitals in Lublin
      region. OBJECTIVE: To describe the pattern of road traffic injuries in Lublin
      county, Poland. METHODS: Review of medical records for the period from January
      2004 to December 2005. RESULTS: Pedestrians accounted for the largest share of
      the Road traffic crash (RTC) injury cases (35.8%) and 46.4% of deaths. The
      highest mortality was observed in motorcycle occupants (7.1%) and victims with
      abdominal injuries (9.8%). Vulnerable road users represented 71.4% of all RTC
      deaths, with mortality 5.8%. Early transfers accounted for 82.5% of cases.
      Mortality in early transfers is 4 times higher than in late transfers.
      CONCLUSIONS: Poland ranks as one of the worst European countries in terms of
      severity and fatal outcomes of road traffic injuries. Groups of road users in
      Poland at the highest risk are pedestrians, cyclists, children and young male
      drivers. The highest mortality rate occurs among road users affected by multiple
      trauma and head/vertebral column injuries. Alleviation of consequences of road
      traffic injuries in Poland may be achieved by coordinated efforts and collective
      responsibility of government, central level agencies, rescue team members and
      community groups.

PMID- 22966735
TI  - IARC: diesel engine exhaust carcinogenic.

PMID- 22966736
TI  - Opportunity for healthy ageing: lessening the burden of adult pneumococcal
      disease in Central and Eastern Europe, and Israel.
AB  - The population of the Region (Central Europe, Eastern Europe, and Israel) is
      ageing, necessitating preventative programmes to maintain a healthy and active
      lifestyle in older age groups. Invasive pneumococcal disease (including
      bacteremic pneumonia, bacteremia without a focus, and meningitis) has higher
      incidence, morbidity and mortality in older adults and is a substantial public
      health burden in the ageing population. Surveillance in the Region establishes a
      significant burden in older adults of invasive pneumococcal disease (IPD), which
      still appears to be under-estimated as compared with other countries, and this
      warrants an improvement in surveillance systems. The largest proportion of IPD in
      adults is bacteremic pneumonia. Community-acquired pneumonia (CAP), largely
      attributable to S. pneumoniae, can be bacteremic or non-bacteremic; the non
      bacteremic forms of CAP also represent a significant burden in the Region. The
      burden of pneumococcal disease can be reduced with programmes of effective
      vaccination. Recommendations on pneumococcal vaccination in adults vary widely
      across the Region. The main barrier to implementation of vaccination programmes
      is low awareness among healthcare professionals on serious heatlh consequences of
      adult pneumococcal disease and of vaccination options. The Expert Panel calls on
      healthcare providers in the Region to improve pneumococcal surveillance, optimize
      and disseminate recommendations for adult vaccination, and support awareness and
      education programmes about adult pneumococcal disease.

PMID- 22966737
TI  - Dietary patterns and their changes in early childhood.
AB  - BACKGROUND: Early childhood is a critical period for shaping and influencing
      feeding behaviours which have implications for future health. Understanding the
      food consumption patterns and their shifts over time can provide guidance to
      health care providers and nutrition specialists who provide nutrition counselling
      and develop nutrition messages. OBJECTIVES: To examine feeding patterns of 1-5
      year old children and their changes with age. METHODS: Across-sectional
      questionnaire study designed to obtain information on basic demographic
      indicators and feeding habits was conducted in Prague and all 13 regions of the
      Czech Republic. The carers of 1,130 children aged 1 to 5 years were approached in
      public places. Obtained data were computerized, descriptive statistics and t
      tests for food intake frequency by age, breast-feeding status, sex, maternal
      education, and domicile were calculated. The difference was considered
      significant when P value was < 0.05. RESULTS: The median duration of breast
      feeding of children not breast-fed at the time of the interview was 9 months;
      29.5% one-year olds were still breast-fed at the time of the interview. Median
      number of meals per day was 4 in 1 and 5 year olds and 5 in children 2 to 4 years
      old. The diet of one-year-olds, albeit with lower fruit and vegetable consumption
      and low fish consumption, was close to recommendations. The milk and milk
      products, fruit, vegetable, and poultry intake frequency significantly decreased
      with age. The meat and grains groups, smoked meat and meat products, sweets, and
      fried food intake frequency significantly increased with age. Fish consumption
      remained low. Higher vegetable intake frequency was associated with breast
      feeding, maternal education, and female sex. Higher fruit consumption was
      associated with breast-feeding and living in Prague. Higher meat group intake
      frequency was associated with male sex. CONCLUSIONS: Our data confirm that the
      dietary habits are formed early in the life. Enhancement of multi-channel
      delivery of nutrition messages for feeding of toddlers and pre-schoolers and for
      the improvement of family eating habits are needed.

PMID- 22966738
TI  - New WHO statistics highlight increases in blood pressure and diabetes, other
      noncommunicable risk factors.

PMID- 22966739
TI  - Excess winter mortality of Roma population in Serbia, 1992-2007.
AB  - OBJECTIVES: Seasonal fluctuations in mortality are associated with age, outdoor
      temperature, influenza, health care provision, lifestyle risk factors and
      economic factors. In the Republic of Serbia almost one half of the Roma
      population lives in poverty and their housing conditions are very poor. The aim
      of this paper is to describe and compare excess winter mortality (EWM) in Roma
      and non-Roma population in Serbia from 1992 to 2007. METHODS: Using the national
      mortality database, this study compares EWM index and rates in Roma and general
      populations in Serbia. Mean winter temperature and ethnicity are analysed against
      the results for relative EWM by multiple linear regression adjusted for age.
      RESULTS: Frequency analysis showed that Roma population had significantly higher
      EWM rate per 10,000 (129.2 vs. 76.6) for all causes, all respiratory diseases
      (26.5 vs. 8.0), and chronic lower respiratory diseases (23.0 vs. 5.2) in
      comparison to non-Roma population. Influenza and pneumonia related deaths
      represented a small proportion of EWM in both populations. Cardiovascular EWM
      rate was slightly higher among non-Roma population. Regression analysis
      demonstrates that Roma ethnicity was associated with significant increase of
      respiratory EWM rate (regression coefficient (B) = 1.49; 95% CI: 0.45-2.54).
      There was no relationship between ethnicity and cardiovascular and all causes EWM
      rates. CONCLUSIONS: Although both Roma and non-Roma populations in Serbia suffer
      from very high rates of excess winter mortality, Roma are significantly more
      vulnerable. EWM rate from chronic lower respiratory diseases is more than four
      times higher among Roma people and suggests that they represent one of the most
      important health problems in Roma population in Serbia.

PMID- 22966740
TI  - Human bio-monitoring study--toxic elements in blood of women.
AB  - The article describes bio-monitoring study concerning recent and long-term
      exposure of Czech women to toxic metals. Blood cadmium, mercury and lead levels
      were measured in groups of women with various life styles, etc., to have
      comparable results in the course of a long study period; a strong emphasis was
      laid on the quality control of the whole process during the study. Higher cadmium
      level was found in smokers compared to non-smokers, lower mercury level was found
      in the group of women who never eat fish. A slight increase of blood lead level
      with age was observed. No significant differences were found between localities
      in a given period. Our results do not differ from those gained in other European
      countries.

PMID- 22966741
TI  - A five year retrospective surveillance; monitoring and evaluation for the
      regional tuberculosis control programme in Mersin, Turkey, 2004-2008.
AB  - AIM: The aim of this study is to identify and evaluate problems in regional
      tuberculosis control studies, using an international tuberculosis indicator.
      METHODS: In this retrospective cohort study, the records of a total of 1,776
      patients diagnosed with tuberculosis, followed up and treated from 2004-2008 in
      Mersin were evaluated. Indicators recommended by the World Health Organization
      were used as assessment criteria. Descriptive statistics were used to summarize
      data. The Mantel-Haenszel test was used for calculation of the risk between
      urban/rural, and between male/ female which were in different age groups.
      RESULTS: During the five year period, new case notification rates were reduced
      and tuberculosis risk shifted to advanced age groups in our region. Tuberculosis
      development risk increased two-fold among males (p < 0.001). One-fifth of the
      tuberculosis cases had been diagnosed without sputum smears. Sputum microscopy
      was not done at the end of the initial phase in one-fifth of patients. During the
      five-year follow-up period, tuberculosis treatment success rate increased from
      83% to 91% and cure rate increased from 49% to 67%. The death rate, treatment
      failure rate, default rate, and transmission rate decreased, and the directly
      observed treatment implementation increased. CONCLUSION: Improvements were seen
      in diagnosis and treatment indicators beginning from 2006; the year when the
      directly supervised treatment application started. However, use of sputum smear
      microscopy is inadequate for the diagnosis and treatment of tuberculosis.
      Tuberculosis control studies should be monitored and evaluated using a
      tuberculosis indicator.

PMID- 22966743
TI  - WHO highlights importance of good hand hygiene for patient safety.

PMID- 22966742
TI  - Efficacy of peginterferon alpha-2A and ribavirin combination therapy in treatment
      naive Estonian patients with chronic hepatitis C.
AB  - AIM: The aim of the study was to assess the efficacy of pegylated interferon (Peg
      IFN) alpha-2a and ribavirin (RBV) combination therapy in treatment-naive patients
      with chronic hepatitis C in Estonia. METHODS: Out of 121 outpatients with chronic
      hepatitis C (73 males, 48 females, aged 19-63) enrolled in the study, 76 were
      infected with HCV genotype 1b and 45 with genotype 3a. At baseline, the viral
      load in 75.2% of patients was higher than 600,000 IU/mL. Histologically, 88.4% of
      patients had fibrosis score F0-2. Patients received 180 microg of Peg-IFN alpha
      2a weekly plus daily ribavirin 1,000 or 1,200 mg, depending on body weight, in
      HCV genotype 1b, or 800 mg/day in genotype 3a infection. RESULTS: The overall
      sustained virologic response (SVR) rate in our study was 60.3%, being
      statistically lower for patients with HCV genotype 1b as compared to patients
      with genotype 3a (46.1% vs. 84.4%, p < 0.05). The non-response and relapse rates
      were significantly higher in patients infected with HCV genotype 1b compared with
      patients infected with genotype 3a (19.7% vs. 2.2%, p = 0.01; and 17.1% vs. 4.4%,
      p = 0.04; respectively). The SVR rate was higher in patients younger than 40
      years compared with older patients (76.4% vs. 47.0%, p < 0.01), regardless of the
      genotype. Thirteen patients infected with HCV genotype 1b required dose reduction
      of PegIFN and/or RBV because of adverse side effects. Nine of them achieved SVR.
      CONCLUSION: HCV genotype and age younger than 40 years predetermined SVR rate in
      treatment-naive Estonian patients with chronic hepatitis C treated with Peg-IFN
      alpha-2a plus ribavirin.

PMID- 22966744
TI  - Early detection of influenza like illness through medication sales.
AB  - Monitoring sales of medications is a potential candidate for an early signal of a
      seasonal influenza epidemic. To test this theory, the data from a traditional,
      consultation-oriented influenza surveillance system were compared to medication
      sales and a predictive model was developed. Weekly influenza-like incidence rates
      from the National Influenza Sentinel Surveillance System were compared to sales
      of seven groups of medications (nasal decongestants, medicines for sore throat
      (MST), antitussives, mucolytics, analgo-antipyretics, non-steroidal anti
      inflamatory drugs (NSAIDs), betalactam antibiotics, and macrolide antibiotics) to
      determine the correlation of medication sales with the sentinel surveillance
      system - and therefore their predictive power. Poisson regression and regression
      tree approaches were used in the statistical analyses. The fact that NSAIDs do
      not exhibit any seasonality and that prescription of antibiotics requires a visit
      to the doctor's office makes the two medication groups inappropriate for
      predictive purposes. The influenza-like illness (ILI) curve is the best matched
      by the mucolytics and antitussives sales curves. Distinct seasonality is also
      observed with MST and decongestants. The model including these four medication
      groups performed best in prediction of ILI incidence rate using the Poisson
      regression model. Sales of antitussives proved to be the best single predictive
      variable for regression tree model. Sales of medication groups included in the
      model were demonstrated to have a predictive potential for early detection of
      influenza season. The quantitative information on medication sales proves to be a
      useful supplementary system, complementing the traditional consultation-oriented
      surveillance system.

PMID- 22966745
TI  - Human development central to changing cancer burden.

PMID- 22966746
TI  - 65th World Health Assembly closes with new global health measures.

PMID- 22966748
TI  - Re-sequencing of ankyrin 3 exon 48 and case-control association analysis of rare
      variants in bipolar disorder type I.
AB  - OBJECTIVES: Genome-wide association studies (GWAS) recently identified ankyrin 3
      (ANK3) as a candidate gene for bipolar disorder type I (BPD-I). Because the GWAS
      suggested multiple common haplotypes associated with BPD-I (with odds ratio
      ~1.3), we hypothesized that rare variants within these common haplotypes might
      increase risk for BPD-I. METHODS: We undertook a project in which the serine-rich
      domain-tail domain (SRD-TD)-encoding exon of ANK3 was amplified from genomic DNA
      (gDNA) of 384 BPD-I patients and re-sequenced by next generation sequencing (NGS;
      SOLiDTM). RESULTS: We confirmed 18 novel mis-sense rare variants and one novel
      insertion/deletion variant within the SRD-TD exon, many of which change amino
      acid residues with extremely high evolutionary conservation. We genotyped most of
      these mis-sense variants in >= 1000 BPD-I and >= 1000 control individuals. We
      found no statistically significant association of any of the rare variants
      detected with BPD-I. CONCLUSIONS: Thus, we conclude that rare variants within the
      re-sequenced structural domains of ANK3 exon 48 do not contribute to BPD-I.

PMID- 22966747
TI  - Identification of an additional protein involved in mannan biosynthesis.
AB  - Galactomannans comprise a beta-1,4-mannan backbone substituted with alpha-1,6
      galactosyl residues. Genes encoding the enzymes that are primarily responsible
      for backbone synthesis and side-chain addition of galactomannans were previously
      identified and characterized. To identify additional genes involved in
      galactomannan biosynthesis, we previously performed deep EST profiling of
      fenugreek (Trigonella foenum-graecum L.) seed endosperm, which accumulates large
      quantities of galactomannans as a reserve carbohydrate during seed development.
      One of the candidate genes encodes a protein that is likely to be a
      glycosyltransferase. Because this protein is involved in mannan biosynthesis, we
      named it 'mannan synthesis-related' (MSR). Here, we report the characterization
      of a fenugreek MSR gene (TfMSR) and its two Arabidopsis homologs, AtMSR1 and
      AtMSR2. TfMSR was highly and specifically expressed in the endosperm. TfMSR,
      AtMSR1 and AtMSR2 proteins were all determined to be localized to the Golgi by
      fluorescence confocal microscopy. The level of mannosyl residues in stem
      glucomannans decreased by approximately 40% for Arabidopsis msr1 single T-DNA
      insertion mutants and by more than 50% for msr1 msr2 double mutants, but remained
      unchanged for msr2 single mutants. In addition, in vitro mannan synthase activity
      from the stems of msr1 single and msr1 msr2 double mutants also decreased.
      Expression of AtMSR1 or AtMSR2 in the msr1 msr2 double mutant completely or
      partially restored mannosyl levels. From these results, we conclude that the MSR
      protein is important for mannan biosynthesis, and offer some ideas about its
      role. 

PMID- 22966749
TI  - Chronic periodontitis and the subsequent risk of trigeminal neuralgia: a 5-year
      follow-up study.
AB  - AIM: This study set out to explore the possibility that chronic periodontitis
      (CP) may also be a condition that could potentially result in secondary or
      symptomatic trigeminal neuralgia (TN) by utilizing a population-based dataset and
      cohort study design in Taiwan. MATERIALS AND METHODS: We included 110,104
      subjects with CP in our study cohort, and randomly selected 110,104 subjects
      without a history of CP as a comparison cohort. We individually tracked each
      patient in this study for a 5-year period to identify those who received a
      subsequent diagnosis of TN. RESULTS: The incidence rate of TN during the 5-year
      follow-up period was 4.40 (95% CI = 3.87-4.98) per 10,000 person-years for
      subjects with CP, and 2.60 (95% CI = 2.20-3.05) per 10,000 person-years in
      comparison subjects. Cox proportional analysis revealed that the adjusted hazard
      ratio (HR) of TN during the 5-year follow-up period for subjects with CP was 1.65
      (95% CI = 1.34-2.03) times higher than that of comparison subjects. However, the
      study subjects who had undergone a gingivectomy or periodontal flap operation did
      not have a higher adjusted risk of TN than comparison subjects (HR = 0.93, 95% CI
      = 0.54-1.61). CONCLUSION: Our study detected a greater risk for TN among patients
      with CP than matched comparison subjects.

PMID- 22966750
TI  - No globally consistent effect of ectomycorrhizal status on foliar traits.
AB  - The concept that ectomycorrhizal plants have a particular foliar trait suite
      characterized by low foliar nutrients and high leaf mass per unit area (LMA) is
      widely accepted, but whether this trait suite can be generalized to all
      ectomycorrhizal clades is unclear. We identified 19 evolutionary clades of
      ectomycorrhizal plants and used a global leaf traits dataset comprising 11,466
      samples across c. 3000 species to test whether there were consistent shifts in
      leaf nutrients or LMA with the evolution of ectomycorrhiza. There were no
      consistent effects of ectomycorrhizal status on foliar nutrients or LMA in the 17
      ectomycorrhizal/non-ectomycorrhizal pairs for which we had sufficient data, with
      some ectomycorrhizal groups having higher and other groups lower nutrient status
      than non-ectomycorrhizal contrasts. Controlling for the woodiness of host species
      did not alter the results. Our findings suggest that the concepts of
      ectomycorrhizal plant trait suites should be re-examined to ensure that they are
      broadly reflective of mycorrhizal status across all evolutionary clades, rather
      than reflecting the traits of a few commonly studied groups, such as the Pinaceae
      and Fagales.

PMID- 22966752
TI  - Personal and trip characteristics associated with safety equipment use by injured
      adult bicyclists: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to estimate use of helmets, lights, and
      visible clothing among cyclists and to examine trip and personal characteristics
      associated with their use. METHODS: Using data from a study of transportation
      infrastructure and injuries to 690 adult cyclists in Toronto and Vancouver,
      Canada, we examined the proportion who used bike lights, conspicuous clothing on
      the torso, and helmets on their injury trip. Multiple logistic regression was
      used to examine associations between personal and trip characteristics and each
      type of safety equipment. RESULTS: Bike lights were the least frequently used
      (20% of all trips) although they were used on 77% of trips at night. Conspicuous
      clothing (white, yellow, orange, red) was worn on 33% of trips. Helmets were used
      on 69% of trips, 76% in Vancouver where adult helmet use is required by law and
      59% in Toronto where it is not. Factors positively associated with bike light use
      included night, dawn and dusk trips, poor weather conditions, weekday trips, male
      sex, and helmet use. Factors positively associated with conspicuous clothing use
      included good weather conditions, older age, and more frequent cycling. Factors
      positively associated with helmet use included bike light use, longer trip
      distances, hybrid bike type, not using alcohol in the 6 hours prior to the trip,
      female sex, older age, higher income, and higher education. CONCLUSIONS: In two
      of Canada's largest cities, helmets were the most widely used safety equipment.
      Measures to increase use of visibility aids on both daytime and night-time
      cycling trips may help prevent crashes.

PMID- 22966751
TI  - Short-term responses of unicellular planktonic eukaryotes to increases in
      temperature and UVB radiation.
AB  - BACKGROUND: Small size eukaryotes play a fundamental role in the functioning of
      coastal ecosystems, however, the way in which these micro-organisms respond to
      combined effects of water temperature, UVB radiations (UVBR) and nutrient
      availability is still poorly investigated. RESULTS: We coupled molecular tools
      (18S rRNA gene sequencing and fingerprinting) with microscope-based
      identification and counting to experimentally investigate the short-term
      responses of small eukaryotes (<6 MUm; from a coastal Mediterranean lagoon) to a
      warming treatment (+3 degrees C) and UVB radiation increases (+20%) at two
      different nutrient levels. Interestingly, the increase in temperature resulted in
      higher pigmented eukaryotes abundances and in community structure changes clearly
      illustrated by molecular analyses. For most of the phylogenetic groups, some
      rearrangements occurred at the OTUs level even when their relative proportion
      (microscope counting) did not change significantly. Temperature explained almost
      20% of the total variance of the small eukaryote community structure (while UVB
      explained only 8.4%). However, complex cumulative effects were detected. Some
      antagonistic or non additive effects were detected between temperature and
      nutrients, especially for Dinophyceae and Cryptophyceae. CONCLUSIONS: This
      multifactorial experiment highlights the potential impacts, over short time
      scales, of changing environmental factors on the structure of various functional
      groups like small primary producers, parasites and saprotrophs which, in
      response, can modify energy flow in the planktonic food webs.

PMID- 22966753
TI  - Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early
      stage breast cancer: a cost-effectiveness evaluation in the German setting.
AB  - OBJECTIVE: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health
      Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of
      adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in
      patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was
      to evaluate the cost-effectiveness of using the assay to inform adjuvant
      chemotherapy decisions in Germany. METHODS: A Markov model was developed to make
      long-term projections of distant recurrence, survival, quality-adjusted life
      expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up
      to 3 node-positive early-stage breast cancer. Scenarios using conventional
      diagnostic procedures or the 21-gene assay to inform treatment recommendations
      for adjuvant chemotherapy were modeled based on a prospective, multi-center trial
      in 366 patients. Transition probabilities and risk adjustment were based on
      published landmark trials. Costs (2011 Euros (?)) were estimated from a sick fund
      perspective based on resource use in patients receiving chemotherapy. Future
      costs and clinical benefits were discounted at 3% annually. RESULTS: The 21-gene
      assay was projected to increase mean life expectancy by 0.06 years and quality
      adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared
      with current clinical practice over a 30-year time horizon. Clinical benefits
      were driven by optimized allocation of adjuvant chemotherapy. Costs from a
      healthcare payer perspective were lower with the 21-gene assay by ~?561 vs
      standard of care. Probabilistic sensitivity analysis indicated that there was an
      87% probability that the 21-gene assay would be dominant (cost and life saving)
      to standard of care. LIMITATIONS: Country-specific data on the risk of distant
      recurrence and quality-of-life were not available. CONCLUSIONS: Guiding decision
      making on adjuvant chemotherapy using the 21-gene assay was projected to improve
      survival, quality-adjusted life expectancy, and be cost saving vs the current
      standard of care women with ER+, HER2- early-stage breast cancer.

PMID- 22966754
TI  - Long-term outcomes after high dose therapy and autologous haematopoietic cell
      rescue for refractory/relapsed Hodgkin lymphoma.
AB  - The standard treatment for patients with refractory or relapsed Hodgkin lymphoma
      (HL) is high-dose chemotherapy and/or radiation with autologous haematopoietic
      cell rescue (AHCR). In this study, we assessed quality of life and evaluated the
      risk of late morbidity and mortality for HL patients who underwent AHCR. One
      hundred and fifty-four patients who underwent AHCR at Stanford University from
      1988 to 2002 and survived >=2 years were evaluated. Median follow-up was 10.2
      years. There were 54 deaths, 34 from HL, 20 from other causes. The 10-year
      cumulative incidence of death from HL or other causes was 21.7% and 12.7%,
      respectively. Thirteen deaths were from second malignancies. The risk ratio of
      second malignancies was 8.0 [95% confidence interval (CI), 4.7-12.6] compared
      with the general population, and 3.0 (95% CI, 1.8-4.8) compared with HL patients
      not undergoing AHCR. The risk ratio of second malignancies was 1.5 (95% CI, 0.9
      2.4) compared with HL patients receiving non-AHCR therapy. Overall quality of
      life did not differ from the general population, but AHCR survivors did note
      reduced functioning and some worse symptoms. AHCR survivors may be at increased
      risk of death from HL and other causes compared with the general population, but
      not compared with the HL population as a whole.

PMID- 22966756
TI  - Hand instrumentation.

PMID- 22966759
TI  - Capsid protein expression and adeno-associated virus like particles assembly in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: The budding yeast Saccharomyces cerevisiae supports replication of
      many different RNA or DNA viruses (e.g. Tombusviruses or Papillomaviruses) and
      has provided means for up-scalable, cost- and time-effective production of
      various virus-like particles (e.g. Human Parvovirus B19 or Rotavirus). We have
      recently demonstrated that S. cerevisiae can form single stranded DNA AAV2
      genomes starting from a circular plasmid. In this work, we have investigated the
      possibility to assemble AAV capsids in yeast. RESULTS: To do this, at least two
      out of three AAV structural proteins, VP1 and VP3, have to be simultaneously
      expressed in yeast cells and their intracellular stoichiometry has to resemble
      the one found in the particles derived from mammalian or insect cells. This was
      achieved by stable co-transformation of yeast cells with two plasmids, one
      expressing VP3 from its natural p40 promoter and the other one primarily
      expressing VP1 from a modified AAV2 Cap gene under the control of the inducible
      yeast promoter Gal1. Among various induction strategies we tested, the best one
      to yield the appropriate VP1:VP3 ratio was 4.5 hour induction in the medium
      containing 0.5% glucose and 5% galactose. Following such induction, AAV virus
      like particles (VLPs) were isolated from yeast by two step ultracentrifugation
      procedure. The transmission electron microscopy analysis revealed that their
      morphology is similar to the empty capsids produced in human cells. CONCLUSIONS:
      Taken together, the results show for the first time that yeast can be used to
      assemble AAV capsid and, therefore, as a genetic system to identify novel
      cellular factors involved in AAV biology.

PMID- 22966760
TI  - The relationship between lignin peroxidase and manganese peroxidase production
      capacities and cultivation periods of mushrooms.
AB  - Mushrooms are able to secrete lignin peroxidase (LiP) and manganese peroxidase
      (MnP), and able to use the cellulose as sources of carbon. This article focuses
      on the relation between peroxidase-secreting capacity and cultivation period of
      mushrooms with non-laccase activity. Methylene blue and methyl catechol
      qualitative assay and spectrophotometry quantitative assay show LiP secreting
      unvaryingly accompanies the MnP secreting in mushroom strains. The growth rates
      of hyphae are detected by detecting the dry hyphal mass. We link the peroxidase
      activities to growth rate of mushrooms and then probe into the relationship
      between them. The results show that there are close relationships between LiP-
      and/or MnP-secretory capacities and the cultivation periods of mushrooms. The
      strains with high LiP and MnP activities have short cultivation periods. However,
      those strains have long cultivation periods because of the low levels of secreted
      LiP and/or MnP, even no detectable LiP and/or MnP activity. This study provides
      the first evidence on the imitate relation between the level of secreted LiP and
      MnP activities and cultivation periods of mushrooms with non-laccase activity.
      Our study has significantly increased the understanding of the role of LiP and
      MnP in the growth and development of mushrooms with non-laccase activity.

PMID- 22966761
TI  - Phosphorus-doped ordered mesoporous carbons with different lengths as efficient
      metal-free electrocatalysts for oxygen reduction reaction in alkaline media.
AB  - Phosphorus-doped ordered mesoporous carbons (POMCs) with different lengths were
      synthesized using a metal-free nanocasting method of SBA-15 mesoporous silica
      with different sizes as template and triphenylphosphine and phenol as phosphorus
      and carbon sources, respectively. The resultant POMC with a small amount of P
      doping is demonstrated as a metal-free electrode with excellent electrocatalytic
      activity for oxygen reduction reaction (ORR), coupled with much enhanced
      stability and alcohol tolerance compared to those of platinum via four-electron
      pathway in alkaline medium. Interestingly, the POMC with short channel length is
      found to have superior electrochemical performances compared to those with longer
      sizes.

PMID- 22966762
TI  - Mapping of within-species segregation distortion in Drosophila persimilis and
      hybrid sterility between D. persimilis and D. pseudoobscura.
AB  - In contrast to the prevailing dogma in the 1990s, recent studies have suggested
      that an evolutionary history of segregation distortion within species may
      contribute to sterility in species hybrids. However, this recent work identified
      segregation distortion exclusively in species hybrids that may never have had an
      evolutionary history of segregation distortion in either parent species. We
      expand on previous work using a strain of Drosophila persimilis exhibiting
      segregation distortion within species to generate QTL maps for segregation
      distortion and hybrid sterility in crosses between D. persimilis and D.
      pseudoobscura. The maps localize regions along the XR contributing to both
      phenotypes, and they indicate one region of overlap between the two maps. This
      overlap could provide preliminary evidence for an association between segregation
      distortion within species and hybrid sterility, but the localizations are
      currently too broad to have confidence in this conclusion. This work is a first
      step towards possibly supporting a genetic conflict model of speciation in this
      system.

PMID- 22966763
TI  - Extensive dissemination of CTX-M-1- and CMY-2-producing Escherichia coli in
      poultry farms in Tunisia.
AB  - We characterized 67 Escherichia coli isolates with reduced susceptibility to
      cefotaxime obtained from 136 samples of healthy broilers housed in 36 Tunisian
      farms. All these isolates harboured blaCTX-M-1 and/or blaCMY-2 genes located
      mostly on self-conjugative IncI1 plasmids. qnrS1, qnrA6 and aac(6')-Ib-cr were
      detected in six isolates. Considerable genetic diversity was detected among
      isolates from different farms. To our knowledge, this is the first detailed
      documentation of a high occurrence of blaCTX-M-1 and blaCMY-2 in E. coli at the
      poultry farm level in Tunisia as well as the first description of plasmid
      mediated quinolone resistance in food animals in Tunisia which may contribute to
      the dissemination of these genes throughout Tunisia. 

PMID- 22966764
TI  - Bioengineering human blood vessel mimics for medical device testing using serum
      free conditions and scaffold variations.
AB  - The three-dimensional culture of blood vessel wall cells now permits the
      construction of a human blood vessel mimic (BVM). Previous studies have used the
      human BVM as a tool to perform in vitro testing of medical devices and imaging
      instrumentation. The purpose of the current study was to enhance this technology
      through both the elimination of animal serum and the modification of scaffold
      properties in human BVM preparation. Additionally, BVMs were implanted with
      vascular stents to observe a potential cellular response to the devices in a
      serum-free environment. Serum-free culture of human adipose-derived stromal
      vascular fraction (SVF) cells was accomplished through sequential adaptation from
      a serum-supplemented medium. The adipose-derived SVF serves as a source of both
      human endothelium and human smooth muscle cells. Utilizing established pressure
      sodding technologies, these cells were incorporated into the luminal surface of
      either expanded polytetrafluoroethylene (ePTFE) tubular scaffolds or electrospun
      poly(l-lactide-co-caprolactone) scaffolds, and the resulting constructs were
      cultivated in a perfusion bioreactor using a serum-free medium. Histological
      analysis of BVMs created using ePTFE scaffolds indicated that a complete lining
      of cells had formed on the inner surfaces of the grafts. Vessel mimics were also
      established under serum-free conditions on the highly porous electrospun tubes,
      resulting in cellularization throughout the scaffold wall in addition to inner
      and outer surfaces. Neither endothelial cells nor smooth muscles cells were
      identified among the mesenchymal cells present in each type of BVM. Bare metal
      stents were deployed within the electrospun BVMs, and after bioreactor perfusion,
      scanning electron microscopy and nuclear-specific bisbenzimide staining confirmed
      the presence of cells on stent surfaces. The outcomes of this study support the
      hypothesis that BVMs developed using serum-free conditions are affected by
      scaffold variations and exhibit tissue growth over implanted medical devices.
      Ultimately, employing serum-free methods could lead to controlled, reproducible
      BVM production and interpretable, human-specific results in studies of device
      tissue interaction, toxicity, and other vascular phenomena; however, comparisons
      to in vivo biological responses and incorporation of defined blood vessel cells
      will be critical to validating the serum-free BVM as an appropriate device
      testing alternative.

PMID- 22966765
TI  - Adolescent growth spurt and growth pattern factors related to the short stature
      of Pygmy hunter-gatherers of Southeast Cameroon.
AB  - INTRODUCTION: Many studies have been carried out to reveal the mechanism of the
      short stature of Pygmy hunter-gatherers in the African rainforest. However, due
      to limitations concerning age-estimation, sample collecting and data analysis,
      their complete growth pattern has not yet been clarified. AIMS: This study has
      three aims as below; (1) to develop a smoothed growth curve, (2) to elucidate the
      presence of adolescent growth spurt and (3) to assess the correlation of growth
      pattern factors to their final short stature. SUBJECTS AND METHODS:
      Anthropometric measurements including height and weight were carried out for 626
      Baka children in southeast Cameroon. LMS method and Preece-Baines function were
      adopted to develop a smoothed growth curve and to assess their growth pattern.
      RESULTS: The height velocity curve and acceleration curve derived from the LMS
      method showed the presence of an adolescent growth spurt. Biological parameters
      indicated their spurt was extremely weak and started at nearly the same time as
      published populations. Height gains between take-off and final height were almost
      equal between Baka children and children in published populations. CONCLUSION:
      The presence of a weak adolescent growth spurt is suggested in the growth pattern
      of Pygmy hunter-gatherers. Moreover, their short adult stature is possibly
      related to growth rate before onset of puberty.

PMID- 22966766
TI  - -374 T/A polymorphism in RAGE gene is associated with onset of diabetes mellitus,
      atherosclerosis, and renal dysfunction in patients with hypertension.
AB  - Receptor of advanced glycation end products (RAGE) is reportedly linked with
      chronic inflammatory diseases due to aging or diabetes. The aim of this study was
      to show how -374 T/A RAGE has an impact on systemic vascular damage and renal
      function. The study subjects were a total of 468 essential hypertension patients
      from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study
      cohort. We prospectively examined the association of -374 T/A RAGE with their
      prognoses and investigated the correlation between -374 T/A RAGE and multiple
      clinical parameters. Kaplan-Meier analysis did not show a significant association
      of -374 T/A RAGE with total mortality or the prevalence of cardiovascular events.
      Carriers of the A allele showed a significantly higher prevalence of diabetes
      mellitus (DM) and lower estimated glomerular filtration rate (eGFR) than subjects
      without this allele. In subjects with DM, carriers of the A allele showed a
      significantly lower eGFR. These significant correlations were only seen in male
      subjects. Carriers of the A allele of -374 T/A RAGE show an independent risk of
      atherosclerosis and reduced renal function in male hypertensive patients with DM.

PMID- 22966768
TI  - Effects of coach leadership and coach-athlete relationship on collective
      efficacy.
AB  - The study examined the independent and combined effects of coach leadership and
      coaching relationships on team efficacy. A total of 150 sport performers from
      football teams across a range of competitive levels completed a multisection self
      report instrument to assess their individual perceptions of the level of
      collective efficacy, the type of coach leadership, and the quality of the coach
      athlete relationship. Multiple regression analyses revealed that perceptions of
      both coach leadership and the coach-athlete relationship predicted variance in
      team efficacy. Overall, the findings suggest that the quality of coach-athlete
      relationships added to the prediction of individuals' collective efficacy beyond
      what was predicted by coaches' behaviors of leadership alone. Limitations and
      future research directions are discussed. 

PMID- 22966767
TI  - Association of clinical and radiographic features with perinephric "sticky" fat.
AB  - BACKGROUND AND PURPOSE: The discovery of thick, adherent, perinephric sticky fat
      (PSF) is relatively common during open or laparoscopic retroperitoneal surgery.
      To our knowledge, however, there has been no previous analysis of clinical or
      radiographic features associated with the development of PSF or of perioperative
      outcomes for those patients in whom it is found. Our objective is to analyze
      potential predictive features and determine whether there is any effect on
      clinical or pathologic outcomes for patients with perinephric sticky fat.
      PATIENTS AND METHODS: Patients undergoing partial nephrectomy or laparoscopic
      cryoablation with available preoperative imaging were identified from 2005 to
      2011. Operative records were reviewed to identify patients with and without PSF.
      Preoperative images and medical records were examined to obtain patient data
      regarding potential predictors as well as clinical and pathologic outcomes.
      RESULTS: A total of 29 patients were identified-16 with PSF and 13 controls.
      Statistically significant factors associated with PSF included sex, tumor size,
      presence of perinephric stranding, tumor >50% exophytic, and thickness of
      perinephric fat (P<0.05). Median total operative time for patients with sticky
      fat was nearly 40 minutes longer than the control group (228 min vs 190 min,
      P<0.05). All four (17%) patients with Fuhrman grade 3 or 4 renal-cell carcinoma
      were from the sticky fat group (P=0.09). CONCLUSIONS: Despite the small sample
      size, multiple possible factors associated with perinephric sticky fat were
      identified and may provide guidance for future investigation of this phenomenon.

PMID- 22966769
TI  - 60 years of development of the journal of integrative plant biology.
AB  - In celebration of JIPB's 60(th) anniversary, this paper summarizes and reviews
      the development process of the journal. To start, we offer our heartfelt thanks
      to JIPB's pioneer Editors-in-Chief who helped get the journal off the ground and
      make it successful. Academic achievement is the soul of academic journals, and
      this paper summarizes JIPB's course of academic development by analyzing it in
      four stages: the first two stages are mostly qualitative analyses, and the latter
      two stages are dedicated to quantitative analyses. Most-cited papers were
      statistically analyzed. Improvements in editing, publication, distribution and
      online accessibility--which are detailed in this paper--contribute to JIPB's
      sustainable development. In addition, JIPB's evaluation index and awards are
      provided with accompanying pictures. At the end of the paper, JIPB's milestones
      are listed chronologically. We believe that JIPB's development, from a national
      journal to an international one, parallels the development of the Chinese plant
      sciences.

PMID- 22966770
TI  - Effect of simulation on nursing knowledge and critical thinking in failure to
      rescue events.
AB  - Failure to rescue events are hospital deaths that result from human error and
      unsafe patient conditions. A failure to rescue event implies that the last and
      best chance to avoid tragedy is not acted on in time to avoid a disaster. Patient
      safety is often compromised by nurses who do not perform accurate assessments
      (vigilance), do not detect clinical changes (surveillance), or do not display
      critical thinking (recognition that something is wrong). This project used
      simulation as a teaching strategy to enhance nursing performance. Medical
      surgical nurses took part in a simulated failure to rescue event in which the
      patient's clinical condition deteriorated rapidly. Nursing knowledge and critical
      thinking improved after the simulation and showed the effectiveness of simulation
      as a teaching strategy to address nursing knowledge and critical thinking skills.

PMID- 22966771
TI  - The lived experience of new nurses: importance of the clinical preceptor.
AB  - BACKGROUND: New nurse internships or residency programs represent one evidence
      based strategy to increase new nurse recruitment and readiness for practice. This
      qualitative study examined the phenomenon of being a new nurse in an internship
      program and explored ways that concernful practices (Diekelmann & Diekelmann,
      2009) present themselves in that program. METHODS: Heideggerian phenomenology was
      used to structure the study of seven nurse interns. Transcripts were made from
      audiotaped conversations of each new nurse and the primary investigator.
      Hermeneutic analysis was used to identify study themes across narratives.
      Sequential transcript analysis was used to connect individual excerpts to create
      a converging conversation of new nurses' lived internship experiences. RESULTS:
      Three study themes defined the meaningfulness of the preceptor-new nurse
      relationship. A converging conversation of new nurse stories linked themes,
      concernful practices (patterns), and interpretation of the experience of being a
      new nurse in an internship program. CONCLUSION: This study amplifies the
      importance of the new nurse-preceptor relationship that supports new nurses'
      transition to practice.

PMID- 22966772
TI  - Building partnerships using student role models for neonatal resuscitation
      simulation.
AB  - BACKGROUND: Although the use of simulation in schools of nursing is becoming
      common, its use in clinical practice is still emerging. This project explored how
      students could contribute to the clinical unit by supporting learning among
      experienced registered nurses who are new to simulation. METHODS: This quasi
      experimental pilot study used a convenience sample of all perinatal nurses who
      participated in a neonatal resuscitation program renewal course in the fall
      quarter at a Midwestern U.S. hospital (N = 88). Satisfaction and confidence in
      learning were compared between groups of nurses who watched a simulation DVD with
      either instructors or students as team members before participating in a neonatal
      resuscitation scenario. RESULTS: The participants viewed the simulation as a
      positive experience. There was no significant difference in satisfaction or
      confidence with the simulation between the two groups. CONCLUSION: There may be
      opportunities for student nurses to make positive contributions to staff
      education on clinical units through simulation.

PMID- 22966773
TI  - Nurses' perceived benefits, barriers, and educational recommendations for using
      family pedigrees in clinical practice.
AB  - BACKGROUND: There is growing emphasis on the use of genetics and genomics,
      including family pedigrees, in nursing education. This study explored nurses'
      perceptions of the benefits, barriers, and educational recommendations related to
      family pedigrees. METHODS: A qualitative design using focus group methods was
      used to gather data from a convenience sample of 28 nurses working at a large
      medical center in the Midwestern United States. RESULTS: Nurses believed that
      factors supporting the use of family pedigrees are clearly identified patient
      benefits, an electronic tool initiated in primary care, and use by multiple
      disciplines. Barriers include lack of ongoing support and possible ethical,
      legal, social, and cultural issues. Educational recommendations include
      clinically relevant patient and family decision making regarding care.
      CONCLUSION: These nurses had positive perceptions of the use of family pedigrees
      in clinical nursing practice. They identified a need for education and stressed
      the importance of specialty-specific case examples to maximize relevance.

PMID- 22966774
TI  - "Beam me up, scotty": designing the future of nursing professional development.
AB  - Experts in nursing education, such as Benner, Sutphen, Leonard, and Day (2010),
      as well as the Institute of Medicine report, The Future of Nursing (2011), agree
      that 21st-century nursing education must change. However, the focus is often on
      academic education rather than practice education. Today's nurses deserve
      exceptional practice education that is built on 21st-century learning principles,
      technologies, and methods as they pursue lifelong, behavior-forming learning.
      This requires four key shifts: (1) using synergistic, collaborative, learner
      centered methods; (2) infusing technology into learning and teaching; (3)
      designing professional development rooted in instructional design best practices;
      and (4) performing comprehensive evaluations of professional development. This
      article explores the necessity for change and encourages nursing professional
      development specialists to boldly go where they have never gone before.

PMID- 22966775
TI  - Redox regulation of glutenin subunit assembly in the plant endoplasmic reticulum.
AB  - The glutenin fraction of wheat storage proteins consists of large polymers in
      which high- and low-molecular-weight subunits are connected by inter-chain
      disulfide bonds. We found that assembly of a low-molecular-weight glutenin
      subunit in the endoplasmic reticulum is a rapid process that leads to
      accumulation of various oligomeric forms, and that this assembly is sensitive to
      perturbation of the cellular redox environment. In endoplasmic reticulum-derived
      microsomes, low-molecular-weight glutenin subunits are subjected to hyper
      polymerization, indicating that cytosolic factors play an important role in
      limiting polymer size. Addition of physiological concentrations of reduced
      glutathione is sufficient to maintain the original polymerization pattern of the
      glutenin subunits upon cytosol dilution. Furthermore, we show that a low
      molecular-weight glutenin subunit can be glutathionylated in endoplasmic
      reticulum-derived microsomes, and that it can be directly reduced by glutathione
      in vitro. These results indicate that glutenin polymerization is sensitive to
      changes in the redox state of the cell, and suggest that the presence of a
      reducing cytosolic environment plays an important role in regulating disulfide
      bond formation in the endoplasmic reticulum of plant cells. 

PMID- 22966777
TI  - Real-time in vivo imaging of fungal migration to the central nervous system.
AB  - Recent technical advances have afforded valuable new insights into the
      pathogenesis of fungal infections in the central nervous system (CNS), which
      continue to cause devastating complications, particularly in immunocompromised
      individuals. To cause CNS mycosis, organisms such as Cryptococcus neoformans
      become blood borne and progress through a series of pathogenic checkpoints that
      culminate in fungal replication in the brain. Critical steps include fungal
      arrest in the vasculature of the brain, interaction and signalling of the fungal
      and endothelial cells leading to transmigration with subsequent parenchymal
      invasion and fungal replication in the CNS. Previous studies that made use of in
      vitro and ex vivo approaches contributed greatly to our understanding of brain
      invasion by fungi. However, the knowledge gained from previous studies relied on
      in vitro models that did not account for vascular haemodynamics. For this reason,
      more refined approaches that model blood flow and vascular anatomy are required,
      andultimately studying fungal invasion and dissemination in vivo. Indeed, in vivo
      imaging (also known as intravital imaging) has emerged as a valuable technique to
      probe host-pathogen interactions. In this review, with a focus on C. neoformans,
      we will provide an overview of the applications of the prior techniques and
      recent advances, their strengths and limitations in characterizing the migration
      of fungi into the brain, and unanswered questions that may provide new directions
      for research.

PMID- 22966776
TI  - Metagenomic and geochemical characterization of pockmarked sediments overlaying
      the Troll petroleum reservoir in the North Sea.
AB  - BACKGROUND: Pockmarks (depressions in the seabed) have been discovered throughout
      the world's oceans and are often related to hydrocarbon seepage. Although high
      concentrations of pockmarks are present in the seabed overlaying the Troll oil
      and gas reservoir in the northern North Sea, geological surveys have not detected
      hydrocarbon seepage in this area at the present time. In this study we have used
      metagenomics to characterize the prokaryotic communities inhabiting the surface
      sediments in the Troll area in relation to geochemical parameters, particularly
      related to hydrocarbon presence. We also investigated the possibility of
      increased potential for methane oxidation related to the pockmarks. Five
      metagenomes from pockmarks and plain seabed sediments were sequenced by
      pyrosequencing (Roche/454) technology. In addition, two metagenomes from seabed
      sediments geologically unlikely to be influenced by hydrocarbon seepage (the
      Oslofjord) were included. The taxonomic distribution and metabolic potential of
      the metagenomes were analyzed by multivariate analysis and statistical
      comparisons to reveal variation within and between the two sampling areas.
      RESULTS: The main difference identified between the two sampling areas was an
      overabundance of predominantly autotrophic nitrifiers, especially Nitrosopumilus,
      and oligotrophic marine Gammaproteobacteria in the Troll metagenomes compared to
      the Oslofjord. Increased potential for degradation of hydrocarbons, especially
      aromatic hydrocarbons, was detected in two of the Troll samples: one pockmark
      sample and one from the plain seabed. Although presence of methanotrophic
      organisms was indicated in all samples, no overabundance in pockmark samples
      compared to the Oslofjord samples supports no, or only low level, methane seepage
      in the Troll pockmarks at the present time. CONCLUSIONS: Given the relatively low
      content of total organic carbon and great depths of hydrocarbon containing
      sediments in the Troll area, it is possible that at least part of the carbon
      source available for the predominantly autotrophic nitrifiers thriving in this
      area originates from sequential prokaryotic degradation and oxidation of
      hydrocarbons to CO2. By turning CO2 back into organic carbon this subcommunity
      could play an important environmental role in these dark oligotrophic sediments.
      The oxidation of ammonia to nitrite and nitrate in this process could further
      increase the supply of terminal electron acceptors for hydrocarbon degradation.

PMID- 22966779
TI  - Number of siblings, birth order, and childhood overweight: a population-based
      cross-sectional study in Japan.
AB  - BACKGROUND: Although several studies have investigated the relationship between
      the number of siblings or birth order and childhood overweight, the results are
      inconsistent. In addition, little is known about the impact of having older or
      younger siblings on overweight among elementary schoolchildren. The present
      population-based study investigated the relationship of the number of siblings
      and birth order with childhood overweight and evaluated the impact of having
      younger or older siblings on childhood overweight among elementary schoolchildren
      in Japan. METHODS: Subjects comprised fourth-grade schoolchildren (age, 9-10
      years) in Ina Town during 1999-2009. Information about subjects' sex, age, birth
      weight, birth order, number of siblings, lifestyle, and parents' age, height, and
      weight was collected by a self-administered questionnaire, while measurements of
      subjects' height and weight were done at school. Childhood overweight was defined
      according to age- and sex-specific cut-off points proposed by the International
      Obesity Task Force. A logistic regression model was used to calculate the odds
      ratio (OR) and 95% confidence intervals (95% CI) of "number of siblings" or
      "birth order" for overweight. RESULTS: Data from 4026 children were analyzed.
      Only children (OR: 2.13, 95% CI: 1.45-3.14) and youngest children (1.56, 1.13
      2.16) significantly increased ORs for overweight compared with middle children. A
      larger number of siblings decreased the OR for overweight (P for trend < 0.001).
      Although there was no statistically significant relationship between a larger
      number of older siblings and overweight, a larger number of younger siblings
      resulted in a lower OR for overweight (P for trend < 0.001). CONCLUSIONS: Being
      an only or youngest child was associated with childhood overweight, and having a
      larger number of younger siblings was negatively associated with overweight. The
      present study suggests that public health interventions to prevent childhood
      overweight need to focus on children from these family backgrounds.

PMID- 22966778
TI  - Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine
      despite its wide scale use as ACT partner drug in Zanzibar.
AB  - BACKGROUND: Zanzibar has recently undergone a rapid decline in Plasmodium
      falciparum transmission following combined malaria control interventions with
      artemisinin-based combination therapy (ACT) and integrated vector control.
      Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for
      uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to
      amodiaquine has been associated with the single nucleotide polymorphism (SNP)
      alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP
      alleles in the parasite population over time might threaten ASAQ efficacy.The aim
      of this study was to assess whether prolonged use of ASAQ as first-line anti
      malarial treatment selects for P. falciparum SNPs associated with resistance to
      the ACT partner drug amodiaquine. METHODS: The individual as well as the combined
      SNP allele prevalence were compared in pre-treatment blood samples from patients
      with uncomplicated P. falciparum malaria enrolled in clinical trials conducted
      just prior to the introduction of ASAQ in 2002-2003 (n = 208) and seven years
      after wide scale use of ASAQ in 2010 (n = 122). RESULTS: There was a
      statistically significant decrease of pfcrt 76T (96-63%), pfmdr1 86Y (75-52%),
      184Y (83-72%), 1246Y (28-16%) and the most common haplotypes pfcrt/pfmdr1 TYYD
      (46-26%) and TYYY (17-8%), while an increase of pfcrt/pfmdr1 KNFD (0.4-14%) and
      KNYD (1-12%). CONCLUSIONS: This is the first observation of a decreased
      prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after
      several years of extensive ASAQ use as first-line treatment for uncomplicated
      malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was
      unexpected considering that all these SNPs have previously been associated with
      amodiaquine resistance. The underlying factors of these results are unclear.
      Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de
      selection by artesunate per se and/or an associated fitness cost might represent
      contributing factors. More detailed studies on temporal trends of molecular
      markers associated with amodiaquine resistance are required to improve the
      understanding of this observation.

PMID- 22966780
TI  - Comparative ranking of human chromosomes based on post-genomic data.
AB  - The goal of the Human Proteome Project (HPP) is to fully characterize the 21,000
      human protein-coding genes with respect to the estimated two million proteins
      they encode. As such, the HPP aims to create a comprehensive, detailed resource
      to help elucidate protein functions and to advance medical treatment. Similarly
      to the Human Genome Project (HGP), the HPP chose a chromosome-centric approach,
      assigning different chromosomes to different countries. Here we introduce a
      scoring method for chromosome ranking based on several characteristics, including
      relevance to health problems, existing published knowledge, and current
      transcriptome and proteome coverage. The score of each chromosome was computed as
      a weighted combination of indexes reflecting the aforementioned characteristics.
      The approach is tailored to the chromosome-centric HPP (C-HPP), and is
      advantageous in that it takes into account currently available information. We
      ranked the human chromosomes using the proposed score, and observed that Chr Y,
      Chr 13, and Chr 18 were top-ranked, whereas the scores of Chr 19, Chr 11, and Chr
      17 were comparatively low. For Chr 18, selected for the Russian part of C-HPP,
      about 25% of the encoded genes were associated with diseases, including cancers
      and neurodegenerative and psychiatric diseases, as well as type 1 diabetes and
      essential hypertension. This ranking approach could easily be adapted to
      prioritize research for other sets of genes, such as metabolic pathways and
      functional categories.

PMID- 22966781
TI  - Altered fatty acid metabolism due to rifampicin-resistance conferring mutations
      in the rpoB Gene of Mycobacterium tuberculosis: mapping the potential of pharmaco
      metabolomics for global health and personalized medicine.
AB  - Abstract   We investigated the use of gas chromatography mass spectrometry (GC
      MS) metabolomics to better characterize rifampicin-resistance by comparing the
      fatty acid metabolomes of two rpoB mutant Mycobacterium tuberculosis strains
      (S522L and S531L) to that of a fully susceptible wild-type parent strain. Using
      the generated GC-MS metabolite data, principal component analysis (PCA) showed a
      clear differentiation between all three sample groups analyzed. We subsequently
      identified those metabolites contributing most to the variation in the data using
      PCA and partial least squares discriminant analysis (PLS-DA). The altered
      metabolite markers detected in the rifampicin-resistant mutants indicate a
      decreased synthesis of various 10-methyl branched-chain fatty acids and cell wall
      lipids, and an increased use of the shorter-chain fatty acids as carbon sources.
      Furthermore, the rpoB S531L mutant, previously reported to occur in well over 70%
      of all clinical rifampicin-resistant M. tuberculosis strains, potentially showed
      a better capacity for using these alternative energy sources, compared to the
      less frequently detected rpoB S522L mutant. This study is the first of its kind
      to associate rifampicin resistance, rpoB mutations, and the beta-subunit of RNA
      polymerase in M. tuberculosis, with an altered fatty acid metabolism, thereby
      demonstrating the role that pharmaco-metabolomics can play in identifying new
      markers associated with drug resistance.

PMID- 22966782
TI  - Internal methane transport through Juncus effusus: experimental manipulation of
      morphological barriers to test above- and below-ground diffusion limitation.
AB  - Aerenchymatous plants can transport methane (CH(4) ) from the root zone to the
      atmosphere, bypassing the surface-oxidizing layers of the soil, yet morphological
      and anatomical factors that govern the transport of methane have rarely been
      critically tested in manipulative experiments. Here, we investigated the methane
      transport capacity of hydroponically grown Juncus effusus, in experiments with
      roots submerged in nutrient solutions sparged with methane (1.16 mmol CH(4) l(
      1)). Through a range of manipulations of the above- and below-ground plant parts,
      we tested the contradictory claims in the literature regarding which sites
      provide the greatest resistance to gas transport. Root manipulations had the
      greatest effect on methane transport. Removing root material reduced methane
      transport significantly, and especially the lateral roots and the root tips were
      important. Cutting of the shoots, with or without subsequent sealing, did not
      alter methane transport significantly. We confirm modelling predictions that the
      limiting factor for methane transport in the tussock forming wetland graminoid,
      J. effusus, is the amount of permeable root surface, estimated using the proxy
      measurement of root length. The aerial tissues do not provide any significant
      resistance to methane transport, and the methane is emitted from the lower 50 mm
      of the shoots.

PMID- 22966783
TI  - The prevalence of reoperation and related risk factors among patients with
      congenital esotropia.
AB  - PURPOSE: To determine the prevalence rate and related risk factors of reoperation
      among patients with congenital esotropia. METHODS: One hundred fifty-seven
      children with congenital esotropia were divided into two groups after at least
      one operation: children with deviation within 10 PD (n = 89; success group) and
      those with deviation greater than 10 PD or history of reoperation (n = 68;
      failure group). The relationship of risk factors such as age at first operation
      and primary congenital esotropia of less than 30 or more than 50 PD and
      accompanying factors such as inferior oblique muscle overaction (> +1),
      dissociated vertical deviation, lateral rectus muscle underaction, and A-V
      pattern with reoperation were studied. Final sensory status of children 5 years
      and older was evaluated by Worth 4-dot and Titmus tests. RESULTS: Reoperation was
      indicated in 32.4% of children who had residual esotropia greater than 15 PD
      after 3 months following their first operation. Congenital esotropia greater than
      30 PD (P = .002) and lateral rectus muscle underaction of -1 to -2 (P < .005),
      were statistically different between the two groups. Initial operation at younger
      than 3 years was more likely to achieve gross stereopsis in children 5 years and
      older (P = .032). CONCLUSION: Congenital esotropia greater than 30 PD and lateral
      rectus muscle underaction were found to be risk factors of reoperation.

PMID- 22966784
TI  - Amblyopia and refractive errors among school-aged children with low socioeconomic
      status in southeastern Turkey.
AB  - PURPOSE: To investigate the prevalence of refractive errors and other eye
      diseases, incidence and types of amblyopia in school-aged children, and their
      relation to gender, age, parental education, and socioeconomic factors. METHODS:
      A total of 21,062 children 6 to 14 years old were screened. The examination
      included visual acuity measurements and ocular motility evaluation.
      Autorefraction under cycloplegia and examination of the external eye, anterior
      segment, media, and fundus were performed. RESULTS: There were 11,118 females and
      9,944 males. The average age was 10.56 +/- 3.59 years. When all of the children
      were evaluated, 3.2% had myopia and 5.9% had hyperopia. Astigmatism 0.50 D or
      greater was present in 14.3% of children. Myopia was associated with older age,
      female gender, and higher parental education. Hyperopia was inversely
      proportional with older age. Spectacles were needed in 4,476 (22.7%) children
      with refractive errors, and 10.6% of children were unaware of their spectacle
      needs. Amblyopia was detected in 2.6% of all children. The most common causes of
      amblyopia were anisometropia (1.2%) and strabismus (0.9%). CONCLUSION: Visual
      impairment is a common disorder in school-aged children. Eye health screening
      programs are beneficial in early detection and proper treatment of refractive
      errors.

PMID- 22966785
TI  - Limitations of encapsidation of recombinant self-complementary adeno-associated
      viral genomes in different serotype capsids and their quantitation.
AB  - We previously reported that self-complementary adeno-associated virus (scAAV)
      type 2 genomes of up to 3.3 kb can be successfully encapsidated into AAV2
      serotype capsids. Here we report that such oversized AAV2 genomes fail to undergo
      packaging in other AAV serotype capsids, such as AAV1, AAV3, AAV6, and AAV8, as
      determined by Southern blot analyses of the vector genomes, although
      hybridization signals on quantitative DNA slot-blots could still be obtained.
      Recently, it has been reported that quantitative real-time PCR assays may result
      in substantial differences in determining titers of scAAV vectors depending on
      the distance between the primer sets and the terminal hairpin structure in the
      scAAV genomes. We also observed that the vector titers determined by the standard
      DNA slot-blot assays were highly dependent on the specific probe being used, with
      probes hybridizing to the ends of viral genomes being significantly
      overrepresented compared with the probes hybridizing close to the middle of the
      viral genomes. These differences among various probes were not observed using
      Southern blot assays. This overestimation of titer is a systemic error during
      scAAV genome quantification, regardless of viral genome sequences and capsid
      serotypes. Furthermore, different serotypes capsid and modification of capsid
      sequence may affect the ability of packaging intact, full-length AAV genomes.
      Although the discrepancy is modest with wild-type serotype capsid and short viral
      genomes, the measured titer could be as much as fivefold different with capsid
      mutant vectors and large genomes. Thus, based on our data, we suggest that
      Southern blot analyses should be performed routinely to more accurately determine
      the titers of recombinant AAV vectors. At the very least, the use of
      probes/primers hybridizing close to the mutant inverted terminal repeat in scAAV
      genomes is recommended to avoid possible overestimation of vector titers.

PMID- 22966786
TI  - Comparison of adeno-associated virus serotypes and delivery methods for cardiac
      gene transfer.
AB  - Cardiac gene transfer is a potentially useful strategy for cardiovascular
      diseases. The adeno-associated virus (AAV) is a common vector to obtain transgene
      expression in the heart. Initial studies conducted in rodents used indirect
      intracoronary delivery for cardiac gene transfer. More recently AAV vectors with
      so-called cardiac tropism have enabled significant cardiac transgene expression
      following intravenous injection. However, a direct comparison of intravenous
      versus intracoronary delivery with rigorous quantification of cardiac transgene
      expression has not been conducted. In the present study we tested the hypothesis
      that intracoronary AAV delivery would be superior to intravenous delivery vis-a
      vis cardiac transgene expression. We compared intravenous and intracoronary
      delivery of AAV5, AAV6, and AAV9 (5*10(11) genome copies per mouse). Using
      enhanced green fluorescent protein as a reporter, we quantified transgene
      expression by fluorescence intensity and Western blotting. Quantitative
      polymerase chain reaction (PCR) was also performed to assess vector DNA copies,
      employing primers against common sequences on AAV5, AAV6, and AAV9. Intracoronary
      delivery resulted in 2.6- to 28-fold higher transgene protein expression in the
      heart 3 weeks after AAV injection compared to intravenous delivery depending on
      AAV serotype. The highest level of cardiac gene expression was achieved following
      intracoronary delivery of AAV9. Intracoronary delivery of AAV9 is a preferred
      method for cardiac gene transfer.

PMID- 22966787
TI  - Altered passive eruption diagnosis and treatment: a cone beam computed tomography
      based reappraisal of the condition.
AB  - AIM: To characterize anatomical features of altered passive eruption (APE)
      affected teeth using cone beam computed tomography (CBCT) and to present a novel
      combined surgical approach to its correction. CLINICAL INNOVATION REPORT: Eighty
      four teeth from 14 subjects affected by APE were subjected to CBCT. Periodontal
      variables were recorded before surgery, and anatomical variables were measured on
      CBCTs. Clinical crown length was measured on study casts. Surgical treatment was
      carried out based on the lengths of the anatomical crowns transferred to a
      surgical guide that served as a reference for the incisions. The mean distance
      between the CEJ and the bone crest was on average <1 mm, facial bone thickness
      was >= 1 mm and soft tissue thickness was >1 mm for every tooth analysed; no
      association between the soft and the hard tissue thicknesses was observed.
      CONCLUSION: The CBCT can be used in the diagnosis and treatment planning of APE
      cases. Anatomically, the APE cases described often presented a thick facial bone
      plate.

PMID- 22966790
TI  - Canonical TGF-beta pathway activity is a predictor of SHH-driven medulloblastoma
      survival and delineates putative precursors in cerebellar development.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Very
      little is known about aggressive forms of this disease, such as metastatic or
      recurrent MBs. In order to identify pathways involved in aggressive MB
      pathophysiology, we performed unbiased, whole genome microarrays on MB tumors at
      both the human and murine levels. Primary human MBs were compared,
      transcriptomically, to their patient-matched recurrent or metastatic tumors.
      Expression profiling was also performed on murine tumors from two spontaneously
      developing MB mouse models (Ptch+/- and Smo/Smo) that present with differing
      clinical severities. At both the human and murine levels we identified
      transforming growth factor-beta (TGF-beta) as a potential contributor to MB
      progression/metastasis. Smad3, a major downstream component of the TGF-beta
      pathway, was also evaluated using immunohistochemistry in malignant human tissues
      and was shown to correlate with MB metastasis and survival. Similarly, Smad3
      expression during development identified a subset of cerebellar neuronal
      precursors as putative cells of origin for the Smad3-positive MBs. To our
      knowledge, this is the first study that links TGF-beta to MB pathogenesis. Our
      research suggests that canonical activation of this pathway leads to better
      prognosis for patients.

PMID- 22966789
TI  - Effect of amiloride and spironolactone on renal tubular function and central
      blood pressure in patients with arterial hypertension during baseline conditions
      and after furosemide: a double-blinded, randomized, placebo-controlled crossover
      trial.
AB  - This study demonstrates that the increased potassium content in the body seems to
      change both the blood pressure and renal tubular function. We wanted to test the
      hypotheses that amiloride and spironolactone induced potassium retention reduces
      ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline
      conditions and after furosemide and that the tubular transport via the epithelial
      sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by
      furosemide in arterial hypertension. Each of three 28-day treatment periods
      (placebo, amiloride, and spironolactone) was completed by a 4-day period with
      standardized diet regarding calories and sodium and water intake. At the end of
      each period, we measured pulse wave velocity (PWV), central systolic blood
      pressure (CSBP), central diastolic blood pressure (CDBP), glomerular filtration
      rate (GFR), free water clearance (CH2O), fractional excretion of sodium (FENa)
      and potassium (FEK), urinary excretion of AQP2 (u-AQP2), urinary excretion of
      gamma-fraction of the ENaC (u-ENaCgamma), and plasma concentrations of renin
      (PRC), angiotensin II (p-Ang II), and aldosterone (p-Aldo) at baseline conditions
      and after furosemide bolus. Ambulatory blood pressure and CBP were significantly
      lowered by amiloride and spironolactone. During 24-hour urine collection and at
      baseline, GFR, CH2O, FENa, FEK, u-AQP2 and u-ENaCgamma were the same. After
      furosemide, CH2O, FENa, FEK, u-AQP2, u-ENaCgamma, PRC, p-Ang II, p-Aldo, PWV and
      CDBP increased after all treatments. However, during amiloride treatment, FEK
      increased to a larger extent than after spironolactone and during placebo after
      furosemide, and CSBP was not significantly reduced. The increases in water and
      sodium absorption via AQP2 and ENaC after furosemide most likely are compensatory
      phenomena to antagonize water and sodium depletion. Amiloride is less effective
      than spironolactone to reduce renal potassium excretion. 

PMID- 22966791
TI  - Validation of a near infrared microscopy method for the detection of animal
      products in feedingstuffs: results of a collaborative study.
AB  - The performance characteristics of a near infrared microscopy (NIRM) method, when
      applied to the detection of animal products in feedingstuffs, were determined via
      a collaborative study. The method delivers qualitative results in terms of the
      presence or absence of animal particles in feed and differentiates animal from
      vegetable feed ingredients on the basis of the evaluation of near infrared
      spectra obtained from individual particles present in the sample. The specificity
      ranged from 86% to 100%. The limit of detection obtained on the analysis of the
      sediment fraction, prepared as for the European official method, was 0.1%
      processed animal proteins (PAPs) in feed, since all laboratories correctly
      identified the positive samples. This limit has to be increased up to 2% for the
      analysis of samples which are not sedimented. The required sensitivity for the
      official control is therefore achieved in the analysis of the sediment fraction
      of the samples where the method can be applied for the detection of the presence
      of animal meal. Criteria for the classification of samples, when fewer than five
      spectra are found, as being of animal origin needs to be set up in order to
      harmonise the approach taken by the laboratories when applying NIRM for the
      detection of the presence of animal meal in feed.

PMID- 22966788
TI  - Childhood acute myeloid leukaemia.
AB  - Although acute myeloid leukaemia (AML) has long been recognized for its
      morphological and cytogenetic heterogeneity, recent high-resolution genomic
      profiling has demonstrated a complexity even greater than previously imagined.
      This complexity can be seen in the number and diversity of genetic alterations,
      epigenetic modifications, and characteristics of the leukaemic stem cells. The
      broad range of abnormalities across different AML subtypes suggests that
      improvements in clinical outcome will require the development of targeted
      therapies for each subtype of disease and the design of novel clinical trials to
      test these strategies. It is highly unlikely that further gains in long-term
      survival rates will be possible by mere intensification of conventional
      chemotherapy. In this review, we summarize recent studies that provide new
      insight into the genetics and biology of AML, discuss risk stratification and
      therapy for this disease, and profile some of the therapeutic agents currently
      under investigation.

PMID- 22966792
TI  - Robot-assisted intrafascial simple prostatectomy: novel technique.
AB  - PURPOSE: We describe our initial experience with intrafascial robot-assisted
      simple prostatectomy (IF-RSP). Potential advantages include reduced blood loss,
      elimination of the need for postoperative bladder irrigation, and elimination of
      the risk of residual or future prostate cancer, without interrupting potency or
      continence. PATIENTS AND METHODS: From June 2011 to March 2012, 10 patients with
      symptomatic prostatomegaly on transrectal ultrasonography (TRUS) (mean 81 g)
      underwent IF-RSP. Three patients had acute urinary retention. Demographic
      perioperative and outcome data were recorded up to 1 month follow-up. RESULTS:
      Average age was 71.7 years (range 60-79 years), estimated blood loss was 375 mL
      (range 150-900 mL), operative time was 106 minutes (range 60-180 min), hospital
      stay was 1 day (range 0-3 days), and Foley catheter duration was 8.9 days (range
      6-14 days). The drain was removed at a mean 2.8 days (range 0-8 days). Mean
      prostate volume on preoperative TRUS was 81 cc (range 47-153 cc). Mean specimen
      weight was 81 g (range 50-150 g). Improvement was noted in the International
      Prostate Symptom Score (preoperative vs postoperative 18.8 vs 1.7) and peak flow
      rate (12.4 vs 33.49 mL/min). Sexual Health Inventory for Men score ranged from 12
      to 24. All patients were completely continent within 1 month postoperatively, and
      sexual function was preserved. One patient had urinary tract infection and one
      patient needed blood transfusion postoperatively. CONCLUSIONS: IF-RSP appears to
      be a feasible procedure in large-volume prostatomegaly. The entire prostate
      tissue is removed without compromising continence and potency. Larger series and
      longer-term follow-up are needed to evaluate the proper place of this approach.

PMID- 22966793
TI  - Commentary: predicting survival in hepatocellular carcinoma patients.

PMID- 22966794
TI  - Commentary: comparisons of upper gastrointestinal bleeding mortality by admission
      time.

PMID- 22966796
TI  - Commentary: time to update the ALT cut-off?

PMID- 22966797
TI  - Letter: are we ready to dismiss use of enteral nutrition in cirrhotic patients
      with jaundice?

PMID- 22966799
TI  - Letter: real-life management of new onset ulcerative colitis and proctitis.

PMID- 22966802
TI  - Letter: non-cirrhotic portal hypertension and end-stage liver disease.

PMID- 22966803
TI  - Letter: effects of oxycodone and tapentadol dosage on gastrointestinal function.

PMID- 22966805
TI  - Extracellular proteome of a highly invasive multidrug-resistant clinical strain
      of Acinetobacter baumannii.
AB  - The study of the extracellular proteomes of pathogenic bacteria is essential for
      gaining insights into the mechanisms of pathogenesis and for the identification
      of virulence factors. Through the use of different proteomic approaches, namely
      Nano-LC and 2DE combined with MALDI-TOF/TOF, we have characterized the
      extracellular proteome of a highly invasive, multidrug-resistant strain of A.
      baumannii (clone AbH12O-A2). This study focused on two main protein fractions of
      the extracellular proteome: proteins that are exported by outer membrane vesicles
      (OMVs) and freely soluble extracellular proteins (FSEPs) present in the culture
      medium of A. baumannii. Herein, a total of 179 nonredundant proteins were
      identified in the OMV protein fraction and a total of 148 nonredundant proteins
      were identified in FSEP fraction. Of the OMV proteins, 39 were associated with
      pathogenesis and virulence, including proteins associated with attachment to host
      cells (e.g., CsuE, CsuB, CsuA/B) and specialized secretion systems for delivery
      of virulence factors (e.g., P. pilus assembly and FilF), whereas the FSEP
      fraction possesses extracellular enzymes with degradative activity, such as
      alkaline metalloprotease. Furthermore, among the FSEP we have detected at least
      18 proteins with a known role in oxidative stress response (e.g., catalase,
      thioredoxin, oxidoreductase, superoxide dismutase). Further assays demonstrated
      that in the presence of FSEPs, bacterial cells withstand much higher
      concentrations of H2O2 showing higher survival rate (approximately 2.5 fold)
      against macrophages. In this study we have identified an unprecedented number of
      novel extracellular proteins of A. baumannii and we provide insight into their
      potential role in relevant processes such as oxidative stress response and
      defense against macrophage attack.

PMID- 22966807
TI  - A tunable route for the synthesis of azomethine imines and beta-aminocarbonyl
      compounds from alkenes.
AB  - Cyclic azomethine imines possessing a beta-aminocarbonyl motif are accessed from
      simple alkene and hydrazone starting materials. A thermal, concerted alkene
      aminocarbonylation pathway involving an imino-isocyanate intermediate is proposed
      and supported by DFT calculations. A notable feature of the process is the steric
      shielding present in the dipoles formed, which allows for facile purification of
      the products by chromatography or crystallization. In addition, a fluorenone
      derived reagent is reported, which provides reactivity with several alkene
      classes and allows for mild derivatization of the dipoles into beta-aminoamides,
      beta-aminoesters, and beta-amino acids.

PMID- 22966808
TI  - Health-related quality of life in Colombia: reference values of the EORTC QLQ
      C30.
AB  - There are normative data of the quality of life (QoL) questionnaire EORTC QLQ-C30
      (the European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire) for several European countries and Korea, but not for Latin
      America. The aim of this study was to provide these normative values for the
      general population in Colombia and to assess differences in terms of age and sex.
      For that reason, a sample of 1500 representatively selected individuals of the
      Colombian population completed the EORTC QLQ-C30 form. Results showed that mean
      scores of the Colombian population are similar to those obtained in European
      countries; whereas the mean values from a Korean study were lower (worse QoL).
      Age and sex differences were found in several scales and symptom items. Linear
      regression analyses were calculated to help quantify the influence of age and
      gender on QoL. Men reported better functioning and less symptoms than women on
      all scales, and older individuals reported worse global scores in terms of
      functioning and lower QoL than younger ones. In sum, the normative values
      presented can be used to assess QoL scores of Latin American cancer patients and
      to compare groups of patients with unequal age and sex distributions.

PMID- 22966809
TI  - An intelligent telecardiology system for offline wireless transmission and remote
      analysis of ECG.
AB  - This paper illustrates a wireless system developed for offline ECG transmission
      and its remote processing. At the transmit end, a standalone embedded system
      collects short duration ECG samples from the source, stores them in a RAM and
      then encodes these using a customized bi-phase modulation for offline
      transmission in ISM band. At the receive end, another embedded system extracts
      ECG data from the demodulated output of the wireless receiver and delivers to a
      desktop computer using the serial port. An application software stores these
      samples in a text file. At first, the bit error and packet error are computed
      from the received dataset. Then, computed ECG wave durations and intervals along
      with lead data plot are generated on a Graphical User Interface for preliminary
      level diagnosis. Test results with synthetic ECG from PTB diagnostic ECG database
      (ptb-db) for short range of communication are reported.

PMID- 22966810
TI  - Status of potential PfATP6 molecular markers for artemisinin resistance in
      Suriname.
AB  - BACKGROUND: Polymorphisms within the PfATP6 gene have been indicated as potential
      molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin
      combination therapy (ACT) was introduced as first-line treatment of the
      uncomplicated malaria cases in Suriname. The aim of this research was to
      determine changes in Suriname in the status of the polymorphic markers in the
      PfATP6 gene before and after the adoption of the ACT-regimen, particularly of the
      S769N mutation, which was reported to be associated with in vitro Artemether
      resistance in the neighboring country French Guiana. METHODS: The PfATP6 gene
      from Plasmodium falciparum parasites in Suriname was investigated in 28 samples
      using PCR amplification and restriction enzyme analysis, to assess and determine
      the prevalence of potentially interesting single nucleotide polymorphisms. The
      polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin
      resistant phenotype were characterized in parasites from three endemic regions
      before and after the adoption of the ACT-regimen. In addition, the status of
      these molecular markers was compared in paired P. falciparum isolates from
      patients with recurring malaria after controlled ACT. RESULTS: All the
      investigated samples exhibit the wild-type genotype at all three positions; L263,
      A623, S769. CONCLUSION: All investigated isolates before and after the adoption
      of the ACT-regimen and independent of endemic region harbored the wild-type
      genotype for the three investigated polymorphisms. The study revealed that
      decreased artemisinin susceptibility could occur independent from PfATP6
      mutations, challenging the assumption that artemisinin resistance is associated
      with these mutations in the PfATP6 gene.

PMID- 22966812
TI  - Prostate alpha/beta revisited -- an analysis of clinical results from 14 168
      patients.
AB  - PURPOSE: To determine the dose response parameters and the fractionation
      sensitivity of prostate tumours from clinical results of patients treated with
      external beam radiotherapy. MATERIAL AND METHODS: The study was based on five
      year biochemical results from 14 168 patients treated with external beam
      radiotherapy. Treatment data from 11 330 patients treated with conventional
      fractionation have been corrected for overall treatment time and fitted with a
      logit equation. The results have been used to determine the optimum alpha/beta
      values that minimise differences in predictions from 2838 patients treated with
      hypofractionated schedules. RESULTS: Conventional fractionation data yielded
      logit dose response parameters for all risk groups and for all definitions of
      biochemical failures. The analysis of hypofractionation data led to very low
      alpha/beta values (1-1.7 Gy) in all mentioned cases. Neglecting the correction
      for overall treatment time has little impact on the derivation of alpha/beta
      values for prostate cancers. CONCLUSIONS: These results indicate that the high
      fractionation sensitivity is an intrinsic property of prostate carcinomas and
      they support the use of hypofractionation to increase the therapeutic gain for
      these tumours.

PMID- 22966811
TI  - Illegitimate recombination: an efficient method for random mutagenesis in
      Mycobacterium avium subsp. hominissuis.
AB  - BACKGROUND: The genus Mycobacterium (M.) comprises highly pathogenic bacteria
      such as M. tuberculosis as well as environmental opportunistic bacteria called
      non-tuberculous mycobacteria (NTM). While the incidence of tuberculosis is
      declining in the developed world, infection rates by NTM are increasing. NTM are
      ubiquitous and have been isolated from soil, natural water sources, tap water,
      biofilms, aerosols, dust and sawdust. Lung infections as well as lymphadenitis
      are most often caused by M. avium subsp. hominissuis (MAH), which is considered
      to be among the clinically most important NTM. Only few virulence genes from M.
      avium have been defined among other things due to difficulties in generating M.
      avium mutants. More efforts in developing new methods for mutagenesis of M. avium
      and identification of virulence-associated genes are therefore needed. RESULTS:
      We developed a random mutagenesis method based on illegitimate recombination and
      integration of a Hygromycin-resistance marker. Screening for mutations possibly
      affecting virulence was performed by monitoring of pH resistance, colony
      morphology, cytokine induction in infected macrophages and intracellular
      persistence. Out of 50 randomly chosen Hygromycin-resistant colonies, four
      revealed to be affected in virulence-related traits. The mutated genes were
      MAV_4334 (nitroreductase family protein), MAV_5106 (phosphoenolpyruvate
      carboxykinase), MAV_1778 (GTP-binding protein LepA) and MAV_3128 (lysyl-tRNA
      synthetase LysS). CONCLUSIONS: We established a random mutagenesis method for MAH
      that can be easily carried out and combined it with a set of phenotypic screening
      methods for the identification of virulence-associated mutants. By this method,
      four new MAH genes were identified that may be involved in virulence.

PMID- 22966813
TI  - The Miles operation--extralevator abdominoperineal excision.

PMID- 22966814
TI  - Precision surgery, precision terminology: the origins and meaning of ELAPE.

PMID- 22966818
TI  - High glucose induced differential expression of lysyl oxidase and its isoform in
      ARPE-19 cells.
AB  - PURPOSE: Lysyl oxidase (LOX) stabilizes the extracellular matrix (ECM) by cross
      linking collagen and elastin molecules. In proliferative diabetic retinopathy
      (PDR), there is ECM remodeling with neovascularization and basement membrane
      changes. While protease activities are well reported, the role of LOX in the
      pathogenesis of diabetic retinopathy is less studied. This study was done to see
      the effect of high glucose on the activity and expression of LOX and its isoforms
      in ARPE-19 cells. MATERIALS AND METHODS: ARPE-19 cells were exposed to high
      glucose up to 48 h, and LOX activity was determined by N-acetyl-3,7
      dihydroxyphenoxazine assay. The mRNA expression of LOX and its isoforms was done
      by real-time PCR and the protein expression by ELISA. Immunohistochemistry for
      LOX was done in epiretinal membrane from PDR. RESULTS: With an increase in
      glucose concentration LOX activity and protein was reduced significantly at 30 mM
      glucose at 48 h. mRNA expression of LOX, LOXL1, and LOXL2 varied with time and
      concentration of glucose. Vascular endothelial growth factor (VEGF) increased the
      LOX activity as well as the mRNA expression. Pigment epithelium-derived factor
      (PEDF) downregulated the mRNA expression of LOX, LOXL1, and LOXL2. The matrix
      metalloprotease (MMP) activity increased significantly with the increase in
      glucose concentration. The diabetic neovascular membrane showed increased
      immunostaining of LOX. CONCLUSIONS: This study suggests that although the LOX
      activity, which is composite of all the isoforms, was reduced under high glucose
      conditions, there was a differential mRNA expression with increased LOX and LOXL1
      and decreased LOXL2 expression.

PMID- 22966819
TI  - The long wait for hybrid sterility in flowering plants.

PMID- 22966820
TI  - Oral health status and behaviours of preschool children in Hong Kong.
AB  - BACKGROUND: Dental caries is a major public health problem in many countries.
      Since the last territority-wide dental survey of Hong Kong preschool children was
      conducted in 2001, a survey to update the information is necessary. This study
      aimed to describe the dental caries experience of preschool children in Hong Kong
      and factors affecting their dental caries status. METHODS: A stratified random
      sample of children from seven kindergartens in Hong Kong was surveyed in 2009.
      Ethical approval from IRB and parental consent was obtained. Clinical
      examinations of the children were performed by two calibrated examiners using
      disposable dental mirrors, an intra-oral LED light and ball-ended periodontal
      probes. A questionnaire to investigate possible explanatory factors for caries
      status was completed by the children's parents. Caries experience was recorded
      using the dmft index. Multifactor-ANOVA was used to study the relationship
      between dental caries experience, and the background and oral health-related
      behaviours of the children. RESULTS: Seven hundred children (53% boys), mean age
      5.3 +/- 0.7 years were examined. The mean dmft score of the surveyed children was
      2.2 and 51% of them had no caries experience (dmft = 0). Most (>95%) of the
      decayed teeth were untreated. Statistically significant correlations were found
      between dental caries experience of the children and their oral health-related
      habits, family income, parental education level and parental dental knowledge.
      CONCLUSIONS: Early childhood dental caries was prevalent among the preschool
      children in Hong Kong. Their caries experience was associated with their oral
      health-related behaviours, socio-economic background, and parental education and
      dental knowledge.

PMID- 22966821
TI  - Measuring positive and negative affect and physiological hyperarousal among
      Serbian youth.
AB  - This study extended previous cross-cultural work regarding the tripartite model
      of anxiety and depression by developing Serbian translations of the Positive and
      Negative Affect Scale for Children (PANAS-C), the Physiological Hyperarousal
      Scale for Children (PH-C), and the Affect and Arousal Scale (AFARS).
      Characteristics of the scales were examined using 449 students (M age = 12.61
      years). Applying item retention criteria established in other studies, PH-C,
      PANAS-C, and AFARS translations with psychometric properties similar to English
      language versions were identified. Preliminary validation of the scales was
      conducted using a subset of 194 students (M age = 12.37 years) who also completed
      measures of anxiety and depression. Estimates of reliability, patterns of
      correlations among scales, and age and gender differences were consistent with
      previous studies with English-speaking samples. Findings regarding scale validity
      were mixed, although consistent with existing literature. Serbian translations of
      the PH-C, PANAS-C, and AFARS mirror the original English-language scales in terms
      of both strengths and weaknesses.

PMID- 22966822
TI  - Low prevalence of antiretroviral resistance among HIV type 1-positive prisoners
      in the Southeast United States.
AB  - Drug-resistant HIV complicates management of HIV infection. Although an estimated
      14% of all HIV-positive persons pass through a prison or jail in the United
      States each year, little is known about the overall prevalence of antiretroviral
      (ARV) resistance in incarcerated persons. All genotypic sequence data on HIV
      positive prisoners in the North Carolina (NC) Department of Corrections (DOC)
      were obtained from LabCorp. Screening for major resistance mutations in protease
      (PI) and reverse transcriptase (NRTI and NNRTI) was done using Genosure and the
      Stanford HIV Database. For subjects with multiple genotype reports, each mutation
      was counted only once and considered present on all subsequent genotypes. Between
      October 2006 and February 2010, the NC DOC incarcerated 1,911 HIV(+) individuals
      of whom 19.2% (n=367) had at least one genotype performed. The overall prevalence
      of a major resistance mutation was 28.3% (95% CI 23.7, 33.0). Among prisoners
      ever exposed to an ARV during incarceration (n=329) prevalence of a major
      resistance mutation was 29.8% (95% CI 24.9, 34.7); resistance by class was 20.4%
      (95% CI 16.0, 24.7) for NRTIs, 19.8% (95% CI 15.5, 24.1) for NNRTIs, and 8.8%
      (95% CI 5.8,11.9) for PIs. Single class drug resistance was most prevalent at
      14.2% (10.2,17.7) followed by dual 12.5% (I8.9,16.0) and triple class 3.3%
      (1.4,5.3) resistance. The three most prevalent mutations were K103N 15.8% (12.0,
      20.2), M184V 14.3% (10.7,18.5), and M41L 4.9% (2.8,7.8). In the NC DOC ARV
      resistance prevalence, dual and triple class drug resistance was moderate over
      the study period. Resistance to PIs was lower than NNRTIs and NRTIs, likely
      reflecting higher usage of these two classes or a lower barrier to resistance.

PMID- 22966823
TI  - Transient myeloproliferative disorder in children with Down syndrome: clarity to
      this enigmatic disorder.
AB  - Children with trisomy 21 have a unique predisposition to develop a
      megakaryoblastic proliferative disease of varying severity during their first 3
      months of life. This disorder exists in no other children or adults without the
      presence of trisomy 21 and only occurs in the fetal or neonatal period of life.
      Its spontaneous resolution in most cases further delineates it from otherwise
      indistinguishable neonatal leukaemias. The identification that GATA1 mutations
      are the leukaemogenic source along with three recently reported prospective
      clinical trials now provide a clearer understanding of this haematopoietic
      disorder. These recent advances in this enigmatic disorder, now known as
      Transient Myeloproliferative Disorder, are reviewed here in order to bring
      clarity to the breadth of organ involvement, the range of severity, the risk
      factors for mortality, the therapeutic options for severe manifestations, the
      natural course of spontaneous resolution regardless of therapy, and the
      elucidation of the subsequent risk for myeloid leukaemia.

PMID- 22966824
TI  - Non-surgical periodontal therapy reduces coronary heart disease risk markers: a
      randomized controlled trial.
AB  - AIM: Periodontal disease elevates systemic inflammatory markers strongly
      associated with coronary heart disease (CHD) risk. The aim of this randomized
      controlled trial was to investigate the effect of non-surgical periodontal
      therapy on systemic C-reactive protein (CRP), fibrinogen and white blood cells in
      CHD patients. MATERIALS AND METHODS: Angiographically proven CHD patients with
      periodontitis (n = 317) were randomized to intervention (n = 212) or control
      group (n = 105). Primary outcome was reduction in serum CRP levels; secondary
      outcomes were reductions in fibrinogen and white blood cells. Periodontal
      treatment included scaling, root planing and oral hygiene instructions.
      Periodontal and systemic parameters were assessed at baseline and at 2-month
      follow-up. Intent-to-treat (ITT) analysis was performed. RESULTS: Study was
      completed by 246 subjects (intervention group = 161; control group = 85).
      Significant improvements in periodontal and systemic parameters were observed in
      intervention group. The number of subjects with CRP > 3mg/L in intervention group
      decreased by 38% and in control group increased by 4%. ITT analysis gave a
      significant (chi(2) =4.381, p = 0.036) absolute risk reduction of 12.5%.
      CONCLUSION: In CHD patients with periodontitis, non-surgical mechanical
      periodontal therapy significantly reduced systemic levels of C-reactive protein,
      fibrinogen and white blood cells.

PMID- 22966825
TI  - Acute and long-term clinical outcome after endoscopic pulmonary vein isolation:
      results from the first prospective, multicenter study.
AB  - INTRODUCTION: The acute and long-term outcome of pulmonary vein isolation (PVI)
      using an endoscopic ablation system (EAS) has only been reported in single-center
      studies. The current prospective, multicenter study assessed the acute and 1-year
      outcome following PVI using the EAS. METHODS AND RESULTS: Seventy-two patients
      (34 female, mean age 58 +/- 10 years) with a history (5 +/- 6 years) of drug
      refractory paroxysmal atrial fibrillation (AF) were included. Endoscopic PVI was
      performed in all patients. Follow-up was based on regular telephone interviews,
      Holter ECG, and transtelephonic ECG recordings. Recurrence was defined as a
      symptomatic and/or documented AF episode >30 seconds following a blanking period
      of 3 months. In 72 patients, a total of 281 pulmonary veins (PVs) were targeted
      and 277/281 (98.6%) PVs were isolated successfully using only the EAS. PV
      stenosis, thrombembolic events, pericardial effusion, pericardial tamponade, and
      phrenic nerve palsy occurred in 0 of 72, 0 of 72, 3 of 72 (4.2%), 4 of 72 (5.6%),
      and in 1 of 72 (1.4%) patients, respectively. Sixty-seven of 72 (93.1%) patients
      completed a follow-up of 365 days and 42 of 67 (62.7%) patients remained in
      stable sinus rhythm after a single procedure. A total of 13 of 25 (52%) patients
      suffering from AF recurrence consented to repeat PVI using conventional
      radiofrequency energy 221 +/- 121 days after the index procedure. LA to PV
      reconduction was found in 30 of 45 (67%) previously isolated PVs. CONCLUSIONS: A
      very high rate of acute electrical PVI is achieved using exclusively the EAS. The
      1-year single-procedure success rate in patients with paroxysmal AF is comparable
      to conventional PVI. PV reconduction is the major determinant for AF recurrence. 

PMID- 22966826
TI  - Radiation exposure during continuous and pulsed fluoroscopy.
AB  - Abstract Background and Purpose: Previous studies using pulsed fluoroscopy have
      shown variable effects on radiation exposure because of the ramp and trail effect
      in older C-arm systems. This study compares radiation delivered in pulsed and
      continuous modalities using a modern C-arm system. MATERIALS AND METHODS:
      Thermoluminescent dosimeters (TLDs) positioned in three body locations directly
      measured radiation dose during simulated ureteroscopy. Thirty pedal activations
      were administered using a pulsed or continuous mode to visualize an implanted
      guidewire and a radiopaque stone. TLD absorbed radiation and image quality were
      compared between imaging modes. RESULTS: Pulsed fluoroscopy delivered less
      radiation compared with continuous fluoroscopy at each site: Anterior skin (0.10
      vs 0.26 mGy, P<0.001), kidney (0.15 vs 0.40 mGy, P<0.001), and posterior skin
      (0.92 vs 2.62 mGy, P<0.001). Mean fluoroscopy time differed between continuous
      and pulsed modes (12.5 vs 3.0 seconds; P<0.001). Fluoroscopy time positively
      correlated with radiation exposure at all sites: Anterior skin (0.017 mGy/s,
      R(2)=0.90), left kidney (0.026 mGy/s, R(2)=0.96), and posterior skin (0.18
      mGy/sec, R(2)=0.98). When evaluated by blinded urologists, 100% of reviewers felt
      pulsed images were adequate to identify guidewire position and 90.5% felt pulsed
      images were adequate for stone localization. CONCLUSION: Pulsed fluoroscopy
      reduced fluoroscopy time by 76% and radiation dose by 64% compared with
      continuous fluoroscopy. Pulsed fluoroscopy images were adequate for most tasks of
      ureteroscopy and should be considered for reduction of radiation during
      ureteroscopy.

PMID- 22966827
TI  - Seasonal and geographical variations in levels of polychlorinated biphenyls (PCB)
      and polybrominated diphenyl ethers (PBDE) in Polish butter fat used as an
      indicator of environmental contamination.
AB  - The aim of this study was to evaluate the seasonal variation/geographical
      distribution of environmental concentration of polychlorinated biphenyls (PCBs)
      and polybrominated diphenyl ethers (PBDEs) across Poland using butter fat as an
      indicator of the contaminants. The average concentration of six indicator PCBs
      determined in the studied samples was 1500 pg g(-1) fat. The average
      concentration of 12 dioxin-like PCBs expressed as lower-bound dioxin-equivalent
      toxicity was 0.684 pg TEQ g(-1) fat. The average total concentration of 14
      investigated PBDE congeners was 105 pg g(-1) fat. Statistically significant
      concentration differences between summer and winter samples were found. The
      results of this study indicate also a significant geographical diversification of
      butter contamination reflecting regional differences in environmental
      contamination. The seasonal variation of PBDE profiles evidences transformation
      of PBDE within the environment.

PMID- 22966828
TI  - An improved algorithm for the detection of genomic variation using short
      oligonucleotide expression microarrays.
AB  - High-throughput microarray experiments often generate far more biological
      information than is required to test the experimental hypotheses. Many microarray
      analyses are considered finished after differential expression and additional
      analyses are typically not performed, leaving untapped biological information
      left undiscovered. This is especially true if the microarray experiment is from
      an ecological study of multiple populations. Comparisons across populations may
      also contain important genomic polymorphisms, and a subset of these polymorphisms
      may be identified with microarrays using techniques for the detection of single
      feature polymorphisms (SFP). SFPs are differences in microarray probe level
      intensities caused by genetic polymorphisms such as single-nucleotide
      polymorphisms and small insertions/deletions and not expression differences. In
      this study, we provide a new algorithm for the detection of SFPs, evaluate the
      algorithm using existing data from two publicly available Affymetrix Barley
      (Hordeum vulgare) microarray data sets and compare them to two previously
      published SFP detection algorithms. Results show that our algorithm provides more
      consistent and sensitive calling of SFPs with a lower false discovery rate.
      Simultaneous analysis of SFPs and differential expression is a low-cost method
      for the enhanced analysis of microarray data, enabling additional biological
      inferences to be made.

PMID- 22966829
TI  - The -Cys-X1-X2-Cys- motif of reduced glutaredoxins adopts a consensus structure
      that explains the low pK(a) of its catalytic cysteine.
AB  - The -Cys-X1-X2-Cys- active site motif is central to the function of enzymes of
      the thioredoxin superfamily, including glutaredoxins. Their chemistry depends on
      the lowered pK(a) of the N-terminal thiolate cysteine of the -Cys-X1-X2-Cys-
      sequence; therefore its structure, dynamics, and electrostatics matter. Much
      information about the glutaredoxin structures was obtained by nuclear magnetic
      resonance (NMR), yet these various NMR structures produced heterogeneous and
      discordant views of the -Cys-X1-X2-Cys- motifs. This study addresses these
      inconsistencies by a computational and experimental investigation of three
      diverse reduced -Cys-X1-X2-Cys- motifs, from human glutaredoxin 1 (hGrx1),
      Escherichia coli glutaredoxin 2 (EcGrx2), and T4 virus glutaredoxin (T4Grx). The
      NMR models do not account for the low pK(a) of the N-terminal cysteine. However,
      extensive investigations of the NMR conformers by simulations yielded consensus
      structures for the -Cys-X1-X2-Cys- motif, with well-defined orientations for the
      cysteines. pK(a) calculations indicated that the consensus structure stabilizes
      the thiolate by local hydrogen bonds. The consensus structures of EcGrx2 and
      T4Grx formed the basis for predicting low pK(a) values for their N-terminal
      cysteines. Subsequent experimental titrations showed that these pK(a) values are
      <5, supporting the validity of the consensus structure. The simulations also
      revisited the conformational dynamics of side chains around the -Cys-X1-X2-Cys-
      motif, which allowed reconciliation of calculated and measured pK(a) values for
      important hGrx1 mutants. The conformational spread of these side chains, which
      differs between NMR and molecular dynamics models, is likely to be relevant to
      substrate recognition. The new structural models determined in this work should
      prove to be valuable in future molecular studies of the glutaredoxins.

PMID- 22966830
TI  - Tissue layer image of the photoreceptor layer in central serous chorioretinopathy
      using SD-OCT.
AB  - BACKGROUND AND OBJECTIVE: To investigate the findings of a tissue layer image of
      the photoreceptor layer, or photoreceptor layer map (PLM), using spectral-domain
      optical coherence tomography (SD-OCT) in central serous chorioretinopathy (CSC).
      PATIENTS AND METHODS: Data scanned using SD-OCT in CSC were processed to obtain
      PLMs, which were analyzed and compared with fluorescein angiography and OCT.
      RESULTS: Among 72 eyes of 69 patients, PLMs depicted subretinal fluid as distinct
      hyporeflective areas in 71 eyes (98.6% sensitivity). Attenuated signals at the
      junction of the inner and outer segments of the photoreceptors in OCT were
      depicted as relative hyporeflective areas corresponding to the areas of previous
      subretinal fluid and its recent reduction. After resolution of subretinal fluid,
      foveal reflectivity was correlated with visual acuity (P = .040; r = 0.41).
      CONCLUSION: PLM is a useful adjuvant image for managing CSC because it shows the
      photoreceptor layer and subretinal fluid as a fundus image.

PMID- 22966832
TI  - Mechanism of amination of beta-keto esters by azadicarboxylates catalyzed by an
      axially chiral guanidine: acyclic keto esters react through an E enolate.
AB  - The mechanism of the reaction between di-tert-butyl azadicarboxylate and 1,3
      dicarbonyl compounds catalyzed by an axially chiral guanidine is investigated by
      density functional theory methods. The results show that the catalyst acts
      simultaneously as a Bronsted base and an acid catalyst, and the mechanism is
      similar to that of the related BINOP organocatalysts. Surprisingly, cyclic and
      acyclic beta-keto esters yield opposite enantiomers; the calculations demonstrate
      that this is a consequence of the preferred enolate geometry in the transition
      structures. Literature evidence suggests that other organocatalytic reactions
      show similar behavior.

PMID- 22966834
TI  - Effect of reimbursement reductions on bone mineral density testing for female
      Medicare beneficiaries.
AB  - BACKGROUND: We examined whether the recent reimbursement reductions on the bone
      mineral density (BMD) test affected BMD testing in female Medicare beneficiaries
      with or without supplemental private health insurance. METHODS: Retrospectively
      analyzing hospital administrative and clinical data on female Medicare
      beneficiaries (n=1320), we reviewed whether participants received BMD testing
      before (January 2004-December 2006) or after (January 2007-December 2009)
      reimbursement reductions for BMD testing. After adjusting for demographics and
      clinical characteristics, we performed Cox proportional hazard regression
      analyses of the BMD test including data from all study participants; we then
      performed separate regression analyses using data with or without supplemental
      private health insurance. RESULTS: In those without supplemental private health
      insurance (n=421), less frequent BMD testing occurred after reimbursement
      reductions for BMD testing (hazard ratio [HR] 0.67, 95% confidence intervals [CI]
      0.34-0.98; p=0.03). By contrast, in the overall participants (n=1320) and those
      with supplemental private health insurance (n=899), the number of BMD tests did
      not change significantly after reimbursement reductions for BMD testing.
      CONCLUSIONS: We found a significant association between reimbursement reductions
      and decrease in BMD tests in female Medicare beneficiaries without supplemental
      private health insurance.

PMID- 22966835
TI  - Ventilation distribution in rats: Part 2--A comparison of electrical impedance
      tomography and hyperpolarised helium magnetic resonance imaging.
AB  - BACKGROUND: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables
      imaging of the air distribution within the lungs. This allows accurate
      determination of the ventilation distribution in vivo. The technique has the
      disadvantages of requiring an expensive helium isotope, complex apparatus and
      moving the patient to a compatible MRI scanner. Electrical impedance tomography
      (EIT) a non-invasive bedside technique that allows constant monitoring of lung
      impedance, which is dependent on changes in air space capacity in the lung. We
      have used He3MRI measurements of ventilation distribution as the gold standard
      for assessment of EIT. METHODS: Seven rats were ventilated in supine, prone, left
      and right lateral position with 70% helium/30% oxygen for EIT measurements and
      pure helium for He3 MRI. The same ventilator and settings were used for both
      measurements. Image dimensions, geometric centre and global in homogeneity index
      were calculated. RESULTS: EIT images were smaller and of lower resolution and
      contained less anatomical detail than those from He3 MRI. However, both methods
      could measure positional induced changes in lung ventilation, as assessed by the
      geometric centre. The global in homogeneity index were comparable between the
      techniques. CONCLUSION: EIT is a suitable technique for monitoring ventilation
      distribution and inhomgeneity as assessed by comparison with He3 MRI.

PMID- 22966836
TI  - Photocontrolled molecular structural transition and doping in graphene.
AB  - We studied chemical doping of trans- and cis-azobenzene on graphene by Raman
      spectroscopy. It was found that the molecule induces hole-doping in graphene
      through charge transfer. Moreover, the doping level in graphene can be reversibly
      modulated by a photocontrolled molecular conformation change. As trans-azobenzene
      isomerizes to the cis configuration under UV irradiation, we probe the dynamic
      molecular structural evolution of azobenzene on graphene by Raman spectroscopy.
      Raman analysis indicates the precise orientation of cis-azobenzene on the
      graphene surface, which brings us further comprehension of the effect of
      conformation change on the electronic properties of graphene. In particular, the
      substantial decreases of the doping level and chemical enhancement of the
      molecular signal are attributed to the weakening of hole transfer from molecule
      to graphene, owing to the lifting of the electron-withdrawing group away from the
      graphene. Moreover, the calculation results exhibit the favorable configuration
      of cis-azobenzene, which is in good agreement with Raman spectroscopic analysis.
      Our results highlight an approach for employing graphene as a promising platform
      for probing molecular conformation transition at the submolecular level by Raman
      spectroscopy.

PMID- 22966838
TI  - Interference resolution moderates the impact of rumination and reappraisal on
      affective experiences in daily life.
AB  - Research has shown that cognitive control processes play a central role in
      emotion regulation. While most research has examined whether individual
      differences in such processes are related to the use of these strategies, a
      crucial next step involves examining whether such differences influence their
      impact on people's feelings, especially in normal daily life. The present study
      examined whether impairments in cognitive control (measured using an affective
      interference resolution task) moderate the impact of using rumination and
      reappraisal on affective experiences in everyday life (assessed using experience
      sampling methods). Multilevel analyses revealed that difficulties removing
      previously relevant negative information from working memory were associated with
      a larger increase in negative affect following rumination, and smaller increase
      and decrease in positive and negative affect, respectively, following
      reappraisal. These findings show that impaired interference resolution for
      negative information aggravates the deleterious effects of rumination and curbs
      the benefits of reappraisal in daily life.

PMID- 22966839
TI  - Whole-body vibration for functional constipation: a single-centre, single
      blinded, randomized controlled trial.
AB  - AIM: The aim of this trial was to determine whether whole-body vibration (WBV)
      induced via a noninvasive oscillation platform could improve symptoms and health
      related quality of life (HRQOL) in patients with chronic functional constipation.
      METHOD: A single-blinded, randomized controlled trial was performed in a single
      hospital in Taiwan. Patients diagnosed with chronic functional constipation, as
      per the Rome III diagnostic criteria, were included and randomized to either the
      WBV treatment or no treatment (control) group. The treatment group received six
      15-min sessions of WBV therapy over a 2-week period. Patients received vibrations
      of 2 mm in amplitude at a frequency of 12 Hz. The primary outcome was whether
      constipation symptoms improved, assessed by the constipation severity instrument
      (CSI) and the secondary outcome measure was whether there was an improvement in
      HRQOL. RESULTS: Whole-body vibration therapy over a 2-week period in patients
      with chronic functional constipation (n = 14) significantly reduced the total CSI
      and obstructive defaecation subscale scores compared with control (n = 13).
      However, WBV did not improve the pain and chronic inertia subscale scores of the
      CSI or HRQOL. CONCLUSION: These findings suggest that low-intensity WBV induced
      via a noninvasive oscillation platform may be an effective therapy for reducing
      symptom severity in patients with chronic functional constipation.

PMID- 22966837
TI  - Metabolic and enzymatic changes associated with carbon mobilization, utilization
      and replenishment triggered in grain amaranth (Amaranthus cruentus) in response
      to partial defoliation by mechanical injury or insect herbivory.
AB  - BACKGROUND: Amaranthus cruentus and A. hypochondriacus are crop plants grown for
      grain production in subtropical countries. Recently, the generation of large
      scale transcriptomic data opened the possibility to study representative genes of
      primary metabolism to gain a better understanding of the biochemical mechanisms
      underlying tolerance to defoliation in these species. A multi-level approach was
      followed involving gene expression analysis, enzyme activity and metabolite
      measurements. RESULTS: Defoliation by insect herbivory (HD) or mechanical damage
      (MD) led to a rapid and transient reduction of non-structural carbohydrates (NSC)
      in all tissues examined. This correlated with a short-term induction of foliar
      sucrolytic activity, differential gene expression of a vacuolar invertase and its
      inhibitor, and induction of a sucrose transporter gene. Leaf starch in defoliated
      plants correlated negatively with amylolytic activity and expression of a beta
      amylase-1 gene and positively with a soluble starch synthase gene. Fatty-acid
      accumulation in roots coincided with a high expression of a
      phosphoenolpyruvate/phosphate transporter gene. In all tissues there was a long
      term replenishment of most metabolite pools, which allowed damaged plants to
      maintain unaltered growth and grain yield. Promoter analysis of ADP-glucose
      pyrophosphorylase and vacuolar invertase genes indicated the presence of cis
      regulatory elements that supported their responsiveness to defoliation. HD and MD
      had differential effects on transcripts, enzyme activities and metabolites.
      However, the correlation between transcript abundance and enzymatic activities
      was very limited. A better correlation was found between enzymes, metabolite
      levels and growth and reproductive parameters. CONCLUSIONS: It is concluded that
      a rapid reduction of NSC reserves in leaves, stems and roots followed by their
      long-term recovery underlies tolerance to defoliation in grain amaranth. This
      requires the coordinate action of genes/enzymes that are differentially affected
      by the way leaf damage is performed. Defoliation tolerance in grain is a complex
      process that can't be fully explained at the transcriptomic level only.

PMID- 22966840
TI  - Translation and validation of the Polish version of the EORTC QLQ-OPT30 module
      for the assessment of health-related quality of life in patients with uveal
      melanoma.
AB  - The purpose of this study was to translate into Polish and validate the European
      Organization for Research and Treatment of Cancer (EORTC) Quality of Life
      Questionnaire Ophthalmic Module (QLQ-OPT30). The QLQ-OPT30 was translated and
      pilot-tested according to EORTC guidelines. Patients were qualified based on the
      histological or ophthalmoscopic and ultrasonographic diagnosis of uveal melanoma.
      Each patient filled out the Polish version of the EORTC Quality of Life
      Questionnaire (EORTC QLQ-C30), the QLQ-OPT30 module and a personal questionnaire.
      Patients were divided into three groups according to treatment type, melanoma
      localisation and possible negative outcomes of the disease or treatment.
      Reliability and validity test were performed and patients' comments were
      analysed. Our study included 94 patients--50 women (53.2%) and 44 men (46.8%) in
      the mean age of 58.4 (+/-13) years. Treatment type and melanoma location did not
      influence the health-related quality of life. The QLQ-OPT30, apart from two
      scales, showed positive internal consistency (Cronbach's alpha coefficients
      range: 0.70-0.88). We found the Polish version of the EORTC QLQ-OPT30 module a
      useful tool for measuring health-related quality of life in uveal melanoma
      patients. Although its discriminative validity is somewhat limited it still can
      be recommended for clinical use in the Polish population.

PMID- 22966841
TI  - Factor structure and psychometric properties of the Pathological Narcissism
      Inventory among Chinese university students.
AB  - The Pathological Narcissism Inventory (PNI) is a multidimensional measure of
      narcissistic pathology. This study examined the factor structure and psychometric
      properties of the PNI in a sample of Chinese university students in Hong Kong.
      Eight hundred and thirty-one students completed an online battery of
      questionnaires assessing narcissistic pathology, self-esteem, unstable sense of
      self, and maladaptive self-defense strategies. Results replicated the 7 first
      order factors and the 2 second-order factors of the PNI. Each of the 7 first
      order factors and the 2 second-order factors had good internal consistency.
      Preliminary findings also supported the concurrent validity of the PNI. The PNI
      appeared to be a valid measure of narcissistic pathology among Chinese. Findings
      of this study suggest that the core pathology of pathological narcissism might
      involve an inflated sense of self-importance that is not substantiated by actual
      achievement, and bearing this unsubstantiated sense of self-importance renders
      narcissists highly susceptible to self-deflation when their narcissistic needs
      are not met.

PMID- 22966842
TI  - Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage
      chemoattractant protein-1, and high-sensitivity C-reactive protein in normal
      tension glaucoma.
AB  - PURPOSE: To investigate the roles of vascular dysregulation and inflammation in
      normal-tension glaucoma (NTG), we determined the plasma levels of endothelin-1
      (ET-1), matrix metalloproteinase-9 (MMP-9), macrophage chemoattractant protein-1
      (MCP-1), and high-sensitivity C-reactive protein (hs-CRP). MATERIALS AND METHODS:
      Forty-five patients with NTG and age-matched 35 healthy controls were enrolled in
      this study. Blood samples from all subjects were assayed for ET-1, MMP-9, MCP-1,
      and hs-CRP concentrations and other systemic factors. RESULTS: There were no
      significant differences in hemoglobin, hematocrit, RBC count, WBC count, platelet
      count, fasting glucose, HbA1c, total cholesterol, triglyceride, LDL, and HDL
      between the NTG and control groups. The systemic levels of ET-1 and MCP-1 were
      significantly higher in the NTG group than in the control group (p = 0.05 and
      0.02, respectively). The MMP-9 and hs-CRP levels were not significantly different
      between the NTG and control groups. CONCLUSIONS: After excluding patients with
      cardiovascular and other systemic diseases, plasma ET-1 and MCP-1 levels were
      elevated in patients with NTG. The MMP-9 and hs-CRP levels were not significantly
      different in NTG. Increased ET-1 and MCP-1 levels suggest that
      ischemia/inflammation may play a role in the pathogenesis of NTG.

PMID- 22966843
TI  - Progesterone and CatSper dependency.

PMID- 22966844
TI  - Association of acculturation and country of origin with self-reported
      hypertension and diabetes in a heterogeneous Hispanic population.
AB  - BACKGROUND: Hispanics are the fasting growing population in the U.S. and
      disproportionately suffer from chronic diseases such as hypertension and
      diabetes. Little is known about the complex interplay between acculturation and
      chronic disease prevalence in the growing and increasingly diverse Hispanic
      population. We explored the association between diabetes and hypertension
      prevalence among distinct U.S. Hispanic subgroups by country of origin and by
      degree of acculturation. METHODS: We examined the adult participants in the 2001,
      2003, 2005, and 2007 California Health Interview Survey (CHIS). Using weighted
      logistic regression stratified by nativity, we measured the association between
      country of origin and self-reported hypertension and diabetes adjusting for
      participants' demographics, insurance status, socio-economic status and degree of
      acculturation measured by citizenship, English language proficiency and the
      number of years of residence in the U.S. RESULTS: There were 33,633 self
      identified Hispanics (foreign-born: 19,988; U.S.-born: 13,645). After
      multivariable adjustment, we found significant heterogeneity in self-reported
      hypertension and diabetes prevalence among Hispanic subgroups. Increasing years
      of U.S. residence was associated with increased disease prevalence. Among all
      foreign-born subgroups, only Mexicans reported lower odds of hypertension after
      adjustment for socioeconomic and acculturation factors. Both U.S.-born and
      foreign-born Mexicans had higher rates of diabetes as compared to non-Hispanic
      whites. CONCLUSIONS: We found significant heterogeneity among Hispanics in self
      reported rates of hypertension and diabetes by acculturation and country of
      origin. Our findings highlight the importance of disaggregation of Hispanics by
      country of origin and acculturation factors whenever possible.

PMID- 22966845
TI  - Short communication: atazanavir-based therapy is associated with higher hepatitis
      C viral load in HIV type 1-infected subjects with untreated hepatitis C.
AB  - We assessed the relationship between atazanavir (ATV)-based antiretroviral
      treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of
      HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based
      on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor
      (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir
      (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4
      and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi
      squared test were used to compare continuous and categorical variables,
      respectively. Multivariate analysis consisted of a stepwise linear regression
      analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included.
      HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9
      6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1
      (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4)
      log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non
      CC). The association was not found in patients carrying HCV genotypes 2/3. The
      linear regression model identified the IL28B genotype and ATV use as independent
      factors associated with HCV RNA levels. ATV-based therapy may be associated with
      a higher HCV RNA viral load in HIV/HCV-coinfected patients.

PMID- 22966846
TI  - Factors affecting the content of pentacyclic triterpenes in Centella asiatica raw
      materials.
AB  - CONTEXT: Pentacyclic triterpenes, mainly, asiatic acid, madecassic acid,
      asiaticoside, and madecassoside are the active constituents of Centella asitica
      (L.) Urban. (Apiaceae). These compounds possess various pharmacological
      activities that have been shown to assist with wound healing and brain
      enrichment. OBJECTIVE: Determination of these active pentacyclic triterpenes in
      extracts from the various parts of C. asiatica plants harvested at different
      times of the year and grown in different environments. MATERIALS AND METHODS: The
      separate plant parts selected were leaves, stolons, petioles, flowers, fruits,
      and nodes with roots. Dried powder from each part was extracted with ethanol by
      microwave-assisted extraction and subjected to determination of their content of
      the four pentacyclic triterpenes using a HPLC method. The effects of the places
      of cultivation as well as harvesting periods on the content of the four
      pentacyclic triterpenes in the extracts were also determined. RESULTS AND
      DISCUSSION: Among the various parts of C. asiatica, the leaves contained the
      highest amount of pentacyclic triterpenes with a total content of pentacyclic
      triterpenes of 19.5 mg/g dry powder. However, the contents of the pentacyclic
      triterpenes in C. asiatica varied according to the place of cultivation and the
      harvesting period. C. asiatica collected from Trang, Thailand gave the highest
      content of total pentacyclic triterpenes (37.2 mg/g dry powder) when harvested in
      March, while those collected from Songkhla, Thailand gave the highest value (37.4
      mg/g dry powder) when collected in December. C. asiatica collected from
      Nakornsrithammarat and Ratchaburi, Thailand gave the lowest content of total
      pentacyclic triterpenes in all experimental harvesting periods.

PMID- 22966847
TI  - Lack of negative impact of Philadelphia chromosome in older patients with acute
      lymphoblastic leukaemia in the thyrosine kinase inhibitor era: comparison of two
      prospective parallel protocols.

PMID- 22966848
TI  - MALDI-based identification of stable hazelnut protein derived tryptic marker
      peptides.
AB  - Food allergy is an important health problem especially in industrialised
      countries. Tree nuts, among which are hazelnuts (Corylus avellana), are typically
      causing serious and life-threatening symptoms in sensitive subjects. Hazelnut is
      used as a food ingredient in pastry, confectionary products, ice cream and meat
      products, therefore undeclared hazelnut can be often present as a cross
      contaminant representing a threat for allergic consumers. Mass spectrometric
      techniques are used for the detection of food allergens in processed foods, but
      limited information regarding stable tryptic peptide markers for hazelnut is
      available. The aim of this study was to detect stable peptide markers from
      modified hazelnut protein through the Maillard reaction and oxidation in a
      buffered solution. Peptides 395Gly-Arg403 from Cor a 11 and 209Gln-Arg217, 351Ile
      Arg363, 464Ala-Arg478 and 401Val-Arg417 from Cor a 9 hazelnut allergens proved to
      be the most stable and could be detected and confirmed with high scores in most
      of the modified samples. The identified peptides can be further used as
      analytical targets for the development of more robust quantitative methods for
      hazelnut detection in processed foods.

PMID- 22966850
TI  - Epidemiology of subarachnoid hemorrhage, patterns of management, and outcomes in
      China: a hospital-based multicenter prospective study.
AB  - AIMS: To conduct a large-scale analysis on epidemiology, management, and outcomes
      of spontaneous subarachnoid hemorrhage (SAH), and to investigate the current
      situation of aneurysm obliteration in China. METHODS: A multicenter prospective
      cohort study involving 132 hospitals throughout China from September 2007 to
      August 2008 was conducted. A total of 651 patients with spontaneous SAH were
      evaluated. RESULTS: The most frequent type of SAH was aneurysmal SAH (77.4%),
      followed by uncommon causes (17.5%) and uncertain etiologies (5.1%). For
      aneurysmal SAH, the cumulative mortality at 28 days, 3 months, 6 months, and 12
      months was 16.9%, 21.2%, 23.6%, and 24.6%, respectively. Obliteration of
      aneurysms, age, Hunt and Hess grade, and history of stroke affected the 12-month
      mortality. In multiple regression analysis, the region, type of hospital,
      patient's age, history of hypertension, and nonintraventricular hemorrhage
      impacted aneurysm obliteration. CONCLUSION: Aneurysmal rupture is the most common
      cause of spontaneous SAH in China. The percentage of aneurysm obliteration is
      still low in China that seems to contribute to long-term mortality. With
      continued training of specialists, proper allocation of healthcare resources, and
      establishment of stroke centers, the rate of securing aneurysms is expected to
      rise.

PMID- 22966849
TI  - Hydrophobic contributions to the membrane docking of synaptotagmin 7 C2A domain:
      mechanistic contrast between isoforms 1 and 7.
AB  - Synaptotagmin (Syt) triggers Ca(2+)-dependent membrane fusion via its tandem C2
      domains, C2A and C2B. The 17 known human isoforms are active in different
      secretory cell types, including neurons (Syt1 and others) and pancreatic beta
      cells (Syt7 and others). Here, quantitative fluorescence measurements reveal
      notable differences in the membrane docking mechanisms of Syt1 C2A and Syt7 C2A
      to vesicles comprised of physiological lipid mixtures. In agreement with previous
      studies, the Ca(2+) sensitivity of membrane binding is much higher for Syt7 C2A.
      We report here for the first time that this increased sensitivity is due to the
      slower target membrane dissociation of Syt7 C2A. Association and dissociation
      rate constants for Syt7 C2A are found to be ~2-fold and ~60-fold slower than Syt1
      C2A, respectively. Furthermore, the membrane dissociation of Syt7 C2A but not
      Syt1 C2A is slowed by Na(2)SO(4) and trehalose, solutes that enhance the
      hydrophobic effect. Overall, the simplest model consistent with these findings
      proposes that Syt7 C2A first docks electrostatically to the target membrane
      surface and then inserts into the bilayer via a slow hydrophobic mechanism. In
      contrast, the membrane docking of Syt1 C2A is known to be predominantly
      electrostatic. Thus, these two highly homologous domains exhibit distinct
      mechanisms of membrane binding correlated with their known differences in
      function.

PMID- 22966851
TI  - Endoscopic treatment with self-expanding metal stents for Crohn's disease
      strictures.
AB  - BACKGROUND: Balloon dilation (with or without steroid injection) is the
      endoscopic treatment of choice for short strictures in Crohn's disease (CD). The
      placement of a stent has only rarely been reported in this setting, and it may be
      a good alternative. AIM: To describe the efficacy of temporary placement of a
      self-expanding metallic stent (SEMS) in the endoscopic treatment of symptomatic
      strictures in CD. METHODS: We included 17 CD patients treated with SEMS (4
      partially covered SEMS and 21 fully covered SEMS) for symptomatic strictures
      refractory to medical and/or endoscopic treatment. RESULTS: We placed 25 stents
      in 17 patients with stenosis (<8 cm), in the colon and in the ileocolonic
      anastomosis. In two cases, two stents were placed in the same endoscopic
      procedure. All except three cases had previously been unsuccessfully treated with
      endoscopic dilatation. The stents were maintained for an average of 28 days (1
      112). The treatment was effective in 64.7% of the patients after a mean follow-up
      time of 60 weeks (5-266). In four cases, removal of the stents was technically
      difficult due to stent impaction (moderate adverse events-AEs) and one patient
      had a proximal stent migration requiring delayed surgery (severe AE). CONCLUSION:
      The placement of self-expanding metallic stent in Crohn's disease maintained over
      a period of 4 weeks is a safe, effective treatment for strictures refractory to
      medical treatment and/or balloon dilatation, and might be an alternative
      endoscopic

PMID- 22966852
TI  - Electrical delay in apically positioned left ventricular leads and clinical
      outcome after cardiac resynchronization therapy.
AB  - INTRODUCTION: In recent studies, an anatomical apical left ventricular (LV) lead
      pacing location has been associated with deleterious outcome after cardiac
      resynchronization therapy (CRT). The differential impact of the LV lead
      electrical location in these patients remains unknown. METHODS AND RESULTS:
      Thirty-one consecutive CRT patients (mean age 71.7 +/- 12.7 years, 55% left
      bundle-branch block [LBBB] morphology) with an apical LV lead and LV lead
      electrical delay (LVLED) were studied. Anatomical LV lead location was determined
      via review of coronary venography and chest radiographs. Electrical location was
      assessed through intraprocedural LVLED measurement. Patients were dichotomized
      into either "long" LVLED (LVLED >= 50% of QRS) or "short" LVLED groups (LVLED <
      50%). Patients in the long LVLED group demonstrated significantly greater freedom
      from a primary composite endpoint of all-cause death, heart failure
      hospitalization, and cardiac transplantation at 2 years (81% vs 30%, P = 0.007 vs
      short LVLED patients). Longer LVLED was also associated with more favorable LV
      remodeling (LV end-systolic volume -41.9 +/- 10.3 mL vs -4.3 +/- 17.2 mL; P =
      0.05), and greater improvement in LV ejection fraction (+9.4 +/- 2.9% vs +2.3 +/-
      7.5%; P = 0.04). Even after multivariate adjustment, LVLED remained an
      independent predictor of the primary composite endpoint (HR 0.47, P = 0.031).
      CONCLUSIONS: Electrical lead localization, as estimated by LVLED >= 50%, is
      associated with improved long-term clinical outcome and measures of LV remodeling
      in patients with apical LV leads. Intraprocedural LVLED assessment may provide
      incremental utility in targeting lead placement even in conventionally
      unfavorable anatomical segments.

PMID- 22966854
TI  - Nickel-catalyzed intermolecular [2 + 2] cycloaddition of conjugated enynes with
      alkenes.
AB  - A nickel-catalyzed intermolecular [2 + 2] cycloaddition of conjugated enynes with
      alkenes has been developed. A variety of electron-deficient alkenes as well as
      electronically neutral norbornene and 1-decene were applicable to this reaction.
      The use of conjugated enynes circumvented possible side rections, such as
      oligomerizations and cyclotrimerizations. The isolation of reaction intermediate
      complexes revealed that the eta(3)-butadienyl coordination is the key for the
      selective formation of cyclobutene.

PMID- 22966853
TI  - The origins and structure of quantitative concepts.
AB  - "Number" is the single most influential quantitative dimension in modern human
      society. It is our preferred dimension for keeping track of almost everything,
      including distance, weight, time, temperature, and value. How did "number" become
      psychologically affiliated with all of these different quantitative dimensions?
      Humans and other animals process a broad range of quantitative information across
      many psychophysical dimensions and sensory modalities. The fact that adults can
      rapidly translate one dimension (e.g., loudness) into any other (e.g., handgrip
      pressure) has been long established by psychophysics research (Stevens, 1975 ).
      Recent literature has attempted to account for the development of the
      computational and neural mechanisms that underlie interactions between
      quantitative dimensions. We review evidence that there are fundamental cognitive
      and neural relations among different quantitative dimensions (number, size, time,
      pitch, loudness, and brightness). Then, drawing on theoretical frameworks that
      explain phenomena from cross-modal perception, we outline some possible
      conceptualizations for how different quantitative dimensions could come to be
      related over both ontogenetic and phylogenetic time scales.

PMID- 22966855
TI  - Corneal graft failure following Nd:YAG laser membranotomy for inadvertent
      retained descemet's membrane after penetrating keratoplasty.
AB  - Retained Descemet's membrane (DM) following penetrating keratoplasty (PKP) is a
      rare finding that may reduce visual acuity following opacification or endanger
      the graft endothelium. The association between Nd:YAG laser membranotomy and
      corneal graft failure is reported. Five of 1,350 patients (0.37%) undergoing PKP
      for pseudophakic bullous keratopathy or graft failure between 1986 and 2008
      presented with inadvertent retained DM located close to the graft endothelium.
      The membrane opacified within 3 to 4 months, reducing the patients' vision.
      Nd:YAG laser membranotomy was performed using low energy and few pulses.
      Patients' visual acuity improved from 6/40 to 6/90 before treatment to 6/15(-) to
      6/20 at 2 weeks following membranotomy. However, the corneal graft decompensated
      within 6 to 8 weeks following this procedure, necessitating repeat PKP, with
      removal of the retained DM. Nd:YAG laser membranotomy may lead to corneal graft
      failure due to shockwave damage created by the laser pulses, focused near the
      endothelial surface.

PMID- 22966856
TI  - Comparison of three markers for the determination of bacterial protein in
      terminal ileal digesta in the growing pig.
AB  - The aim of the study was to compare three methods commonly used to determine the
      concentrations of bacterial protein in digesta collected from the terminal ileum
      of growing pigs that had been fed a casein-based diet. The amounts of bacterial
      protein in terminal ileal digesta were determined using three different markers:
      2.6-diaminopimelic acid (DAPA) and the d-amino acids, d-aspartic acid (d-Asp) and
      d-glutamic acid (d-Glu). The effectiveness of each marker was compared against a
      control based on physical fractionation by centrifugation. The total bacterial
      protein concentrations derived from the markers d-Asp and d-Glu were
      significantly different (p = 0.05) to those calculated from DAPA and the control,
      but there was no difference between DAPA and the control. The percentage of
      bacterial nitrogen ranged from 40% to 52% dependent on the marker used. Bacterial
      protein expressed as a percentage of the total protein, ranged from 48% to 62%, a
      substantial proportion of which (12-28%) was derived from lysed bacterial cells.
      Statistical correlations between the estimation methods were low. Such poor
      correlation between the markers may be the result of random errors such as
      variance in the epimerization of the two d-amino acids during protein hydrolysis.
      DAPA was accepted as a reliable marker for determining microbial protein in ileal
      digesta. 

PMID- 22966857
TI  - Plasmon ruler with angstrom length resolution.
AB  - We demonstrate a plasmon nanoruler using a coupled film nanoparticle (film-NP)
      format that is well-suited for investigating the sensitivity extremes of
      plasmonic coupling. Because it is relatively straightforward to functionalize
      bulk surface plasmon supporting films, such as gold, we are able to precisely
      control plasmonic gap dimensions by creating ultrathin molecular spacer layers on
      the gold films, on top of which we immobilize plasmon resonant nanoparticles
      (NPs). Each immobilized NP becomes coupled to the underlying film and functions
      as a plasmon nanoruler, exhibiting a distance-dependent resonance red shift in
      its peak plasmon wavelength as it approaches the film. Due to the uniformity of
      response from the film-NPs to separation distance, we are able to use extinction
      and scattering measurements from ensembles of film-NPs to characterize the
      coupling effect over a series of very short separation distances-ranging from 5
      to 20 A-and combine these measurements with similar data from larger separation
      distances extending out to 27 nm. We find that the film-NP plasmon nanoruler is
      extremely sensitive at very short film-NP separation distances, yielding spectral
      shifts as large as 5 nm for every 1 A change in separation distance. The film-NP
      coupling at extremely small spacings is so uniform and reliable that we are able
      to usefully probe gap dimensions where the classical Drude model of the
      conducting electrons in the metals is no longer descriptive; for gap sizes
      smaller than a few nanometers, either quantum or semiclassical models of the
      carrier response must be employed to predict the observed wavelength shifts. We
      find that, despite the limitations, large field enhancements and extreme
      sensitivity persist down to even the smallest gap sizes.

PMID- 22966859
TI  - Subspecialist emergency management of diverticulitis is associated with reduced
      mortality and fewer stomas.
AB  - AIM: The aim of the study was to compare outcomes for emergency management of
      diverticulitis before and after the creation of a regional subspecialist
      colorectal unit. METHOD: We retrieved data on all emergency admissions for
      diverticulitis from the regional surgical audit database and compared results
      before (January 1998 to August 2002) and after (August 2002 to December 2008)
      establishment of the subspecialist colorectal surgery unit in August 2002.
      Additional data were retrieved from electronic patient records. The primary
      outcome measures were mortality and rate of primary anastomosis following
      resection. RESULTS: There were 879 patients before and 1280 patients after
      subspecialization. Nonoperative management was undertaken in approximately 80% of
      cases. Total mortality fell from 3.3 to 1.5% (P = 0.008), attributable to reduced
      operative mortality (9.6 to 4.2%; P = 0.019). The primary anastomosis rate for
      all left colon resections increased from 50.3 to 77.9%; P < 0.0001. Stoma
      formation of any type fell from 46.6 to 27.7%; P < 0001). CONCLUSION: Emergency
      management of diverticulitis by subspecialist colorectal surgeons is associated
      with low overall and operative mortality whilst safely achieving high rates of
      primary anastomosis.

PMID- 22966858
TI  - The small GTPase RhoG mediates glioblastoma cell invasion.
AB  - BACKGROUND: The invasion of glioblastoma cells into regions of the normal brain
      is a critical factor that limits current therapies for malignant astrocytomas.
      Previous work has identified roles for the Rho family guanine nucleotide exchange
      factors Trio and Vav3 in glioblastoma invasion. Both Trio and Vav3 act on the
      small GTPase RhoG. We therefore examined the role of RhoG in the invasive
      behavior of glioblastoma cells. RESULTS: We found that siRNA-mediated depletion
      of RhoG strongly inhibits invasion of glioblastoma cells through brain slices ex
      vivo. In addition, depletion of RhoG has a marginal effect on glioblastoma cell
      proliferation, but significantly inhibits glioblastoma cell survival in colony
      formation assays. We also observed that RhoG is activated by both HGF and EGF,
      two factors that are thought to be clinically relevant drivers of glioblastoma
      invasive behavior, and that RhoG is overexpressed in human glioblastoma tumors
      versus non-neoplastic brain. In search of a mechanism for the contribution of
      RhoG to the malignant behavior of glioblastoma cells, we found that depletion of
      RhoG strongly inhibits activation of the Rac1 GTPase by both HGF and EGF. In line
      with this observation, we also show that RhoG contributes to the formation of
      lamellipodia and invadopodia, two functions that have been shown to be Rac1
      dependent. CONCLUSIONS: Our functional analysis of RhoG in the context of
      glioblastoma revealed a critical role for RhoG in tumor cell invasion and
      survival. These results suggest that targeting RhoG-mediated signaling presents a
      novel avenue for glioblastoma therapy.

PMID- 22966860
TI  - Superhydrophobic hierarchical honeycomb surfaces.
AB  - Two-dimensional hexagonally ordered honeycomb surfaces have been created by
      solvent casting polybutadiene films under controlled humidity. Subsequent CF(4)
      plasmachemical fluorination introduces cross-linking and surface texturing,
      leading to hierarchical surfaces with roughness on both the 10 MUm (honeycomb)
      and micrometer (texturing) length scales. For microliter droplets, these display
      high water contact angle values (>170 degrees ) in combination with low contact
      angle hysteresis (i.e., superhydrophobicity) while displaying bouncing of
      picoliter water droplets. In the case of picoliter droplets, it is found that
      surfaces which exhibit similar static contact angles can give rise to different
      droplet impact dynamics, governed by the underlying surface topography. These
      studies are of relevance to technological processes such as rapid cooling,
      delayed freezing, crop spraying, and inkjet printing.

PMID- 22966861
TI  - Management of precancerous lesions prior to conception and during pregnancy: a
      narrative review of the literature.
AB  - Special considerations aiming at preserving reproductive function have to be
      implemented when treating young patients with precancerous lesions of the lower
      genital tract. These high-grade lesions may progress into invasive cancer if left
      untreated. Currently, there are limited data on the impact of vulvar and vaginal
      precancerous lesions on fertility and its management during pregnancy. However,
      management and outcomes for cervical lesions have been extensively reported. The
      main approach for vulvar and vaginal lesions are maintaining anatomical function
      and cosmetics; whereas, treatment options for cervical precancerous lesions range
      from observation, cryotherapy or the more aggressive conisation. Gestational age
      is the most important factor in determining expectant management or surgical
      intervention. This narrative review draws attention to the relevant aspects of
      precancerous lesions of the lower genital tract, the potential effects and
      management prior to conception and during pregnancy.

PMID- 22966863
TI  - Study of virulence in field isolates of infectious pancreatic necrosis virus
      obtained from the northern part of Norway.
AB  - In order to study the variety of infectious pancreatic necrosis virus (IPNV)
      strains involved in outbreaks of infectious pancreatic necrosis (IPN) in Atlantic
      salmon fish farms, samples were collected from 19 different outbreaks of IPN in
      the northern part of Norway. The main objective of this study was to examine
      whether IPNV isolates of different virulence were involved in the outbreaks and
      could explain the variable IPN protection observed in vaccinated post-smolts in
      the field. Both the molecular basis of virulence of all field isolates and
      virulence expressed by mortality after bath challenge of unvaccinated post-smolts
      with eight of the isolates were studied. Very little variation among the field
      isolates was detected when the 578-bp variable region encoding the VP2 protein
      known to be involved in virulence was sequenced. The cumulative mortality after
      experimental challenge with field isolates genetically characterized as highly
      virulent was always high (40-56%), while the cumulative mortality of the same
      strains in vaccinated post-smolts during the field outbreaks varied from 1 to
      50%. Although the tested samples came from fish vaccinated with the same vaccine
      product, the protection against IPN varied. These results demonstrate that
      differences in virulence of the isolates were not the main reason for the
      variation in mortality in the field outbreaks. Most of the field isolates were of
      high virulence, which is shown in experimental challenges to be important for
      mortality, but clearly other factors that might affect the susceptibility of IPN
      also play an important role in the outcome of an IPNV infection.

PMID- 22966862
TI  - Influence of time between last myocardial infarction and prophylactic implantable
      defibrillator implant on device detections and therapies. "Routine Practice" data
      from the SEARCH MI registry.
AB  - BACKGROUND: A multicenter European Registry, SEARCH-MI, was instituted in the
      year 2002 in order to assess patients' outcomes and ICD interventions in patients
      with a previous MI and depressed LV function, treated with an ICD according to
      MADIT II results. In this analysis, we evaluate the influence of the time elapsed
      between last myocardial infarction (MI) and prophylactic cardioverter
      defibrillator (ICD) implant on device activations. METHODS: 643 patients with
      left ventricular dysfunction (mean LVEF 26 +/- 5%) and NYHA class I-III were
      prospectively followed for 1.8 +/- 1.2 years in a multicenter registry. The
      population was divided into 3 groups according to the time between last MI and
      ICD implant: [1] from 40 days to less than 1.5 years; [2] from 1.5 to less than 7
      years and [3] at least 7 years. RESULTS: The cumulative incidence of ventricular
      tachyarrhymias and appropriate device therapy (ATP or shock) were higher in
      patients implanted longer time from last MI (Gray's Test p=0.002 and p=0.013
      respectively). No significant differences were seen in all cause mortality
      (Gray's Test p=0.618) or sudden cardiac death across the MI stratification groups
      (Gray's Test p=0.663). CONCLUSIONS: Patients implanted with an ICD longer after
      the MI have a higher chance of presenting ventricular tachyarrhythmias and
      appropriate ICD therapy, while no differences were seen in overall mortality.
      These observations may be important for improving patient targeting in sudden
      death prevention.

PMID- 22966864
TI  - The effect of endogenous estrogen on Doppler-estimated right ventricular systolic
      pressure during exercise.
AB  - We evaluated the effect of endogenous estrogen levels on exercise-related changes
      in right ventricular systolic pressure (RVSP) of healthy, eumenorrheic, sedentary
      women. Volunteers were studied at two separates phases of the menstrual cycle (LO
      and HI estrogen phases), exercised on a semi-supine ergometer with escalating
      workload and monitored continuously by 12-lead ECG and automated blood pressure
      cuff. At each exercise stage, Doppler echocardiography measurements were obtained
      and analyzed to determine RVSP. Fourteen subjects (age 24 +/- 5) were studied.
      Exercise duration was significantly higher on the HI estrogen day, but no
      significant differences in hemodynamic response to exercise were found between
      the two study days. There were also no significant differences with respect to
      heart rate (HR) acceleration during early exercise, as well as resting and peak
      RVSP, HR, blood pressure, and rate pressure product. Doppler-estimated RVSP
      demonstrated a linear relationship to HR at a ratio of 1 mm Hg (1 mm Hg =
      133.3224 Pa) for every 5 bpm (beats per minute) increase in HR. There were no
      differences in the slope of this relationship between HI and LO estrogen phases
      of the menstrual cycle. Our findings did not demonstrate any effect of endogenous
      estrogen levels on the modulation of the pulmonary vascular response to exercise
      in healthy women.

PMID- 22966865
TI  - A trans-disciplinary approach to the evaluation of social determinants of health
      in a Hispanic population.
AB  - BACKGROUND: Individual and community health are adversely impacted by disparities
      in health outcomes among disadvantaged and vulnerable populations. Understanding
      the underlying causes for variations in health outcomes is an essential step
      towards developing effective interventions to ameliorate inequalities and
      subsequently improve overall community health. Working at the neighborhood scale,
      this study examines multiple social determinates that can cause health
      disparities including low neighborhood wealth, weak social networks, inadequate
      public infrastructure, the presence of hazardous materials in or near a
      neighborhood, and the lack of access to primary care services. The goal of this
      research is to develop innovative and replicable strategies to improve community
      health in disadvantaged communities such as newly arrived Hispanic immigrants.
      METHODS/DESIGN: This project is taking place within a primary care practice-based
      research network (PBRN) using key principles of community-based participatory
      research (CBPR). Associations between social determinants and rates of
      hospitalizations, emergency department (ED) use, and ED use for primary care
      treatable or preventable conditions are being examined. Geospatial models are in
      development using both hospital and community level data to identify local areas
      where interventions to improve disparities would have the greatest impact. The
      developed associations between social determinants and health outcomes as well as
      the geospatial models will be validated using community surveys and qualitative
      methods. A rapidly growing and underserved Hispanic immigrant population will be
      the target of an intervention informed by the research process to impact
      utilization of primary care services and designed, deployed, and evaluated using
      the geospatial tools and qualitative research findings. The purpose of this
      intervention will be to reduce health disparities by improving access to, and
      utilization of, primary care and preventative services. DISCUSSION: The results
      of this study will demonstrate the importance of several novel approaches to
      ameliorating health disparities, including the use of CBPR, the effectiveness of
      community-based interventions to influence health outcomes by leveraging social
      networks, and the importance of primary care access in ameliorating health
      disparities.

PMID- 22966866
TI  - Multicultural personality questionnaire: development of a short form.
AB  - This study reports on the development of the Multicultural Personality
      Questionnaire-Short Form among 511 participants. Using a split-sample scale
      validation design, Study 1 (N = 260) employed a principal component analysis and
      rigorous item selection criteria to extract a 40-item short form (MPQ-SF) from
      the original 91-item Multicultural Personality Questionnaire (MPQ; van der Zee &
      van Oudenhoven, 2000, 2001). In Study 2 (N = 251), the MPQ-SF was subjected to
      confirmatory factor analysis and resulted in a reasonably good fit to the data
      (comparative fit index = .94; root mean squared error of approximation = .066).
      Satisfactory coefficient alphas and high correlations with the original scales
      were found. Moreover, relationships with related scales were largely in the
      predicted direction. Specific directions for follow-up research are posited.

PMID- 22966867
TI  - Prospective study of histomorphometry, biochemical bone markers and bone
      densitometric response to pamidronate in beta-thalassaemia presenting with
      osteopenia-osteoporosis syndrome.
AB  - This study aimed to evaluate bone remodelling disorders in thalassaemia by using
      pamidronate (PD) infusion with or without hormone replacement therapy (HRT) as a
      diagnostic-therapeutic tool. In this prospective study, 24 adult thalassaemia
      major (TM) and 10 thalassaemia intermedia (TI) patients received either PD and
      HRT or HRT only (controls) for 3 years. Eugonadal patients with TI had PD only.
      Bone remodelling was assessed by dual energy X ray absorptiometry (DXA scan),
      type 1-collagen biochemical bone markers (BBM) and histomorphometry of iliac
      crest biopsy before and after PD. As a group, thalassaemics had a significant
      improvement in spinal and femoral bone mineral density Z scores following PD (P <
      0.01) compared to the controls. Although BBM were comparable pre-therapy, they
      were significantly lower in the PD cohort (P < 0.001) compared to the control
      group. All patients had osteopenia, diminished osteoid formation and bone volume
      on histomorphometry pre-therapy with high turnover bone disease (HTO) in TM and
      low-turnover disease (LTO) in TI. In TM, bone volume improved significantly,
      whereas TI patients showed little or no response to PD. In conclusion,
      histomorphometry data suggest that TM patients have a distinct pathology of high
      turnover bone disease compared to TI patients, who have low-turnover disease.

PMID- 22966868
TI  - Is there a relationship between fatigue perception and the serum levels of
      thyrotropin and free thyroxine in euthyroid subjects?
AB  - BACKGROUND: Thyrotoxicosis and hypothyroidism are associated with fatigue. Here
      we studied euthyroid subjects to determine if there was a relationship between
      serum thyrotropin (TSH), free thyroxine (FT(4)) and thyroperoxidase antibodies
      and fatigue. METHODS: A total of 5897 participants of the Nijmegen Biomedical
      Study received a questionnaire and serum TSH (normal range 0.4-4.0 mIU/L) and
      FT(4) (normal range 8-22 pmol/L) were measured. Fatigue was evaluated by the RAND
      36 and the shortened fatigue questionnaire (SFQ). RESULTS: Euthyroid subjects
      with a serum TSH level of 0.4-1.0 mIU/L had a lower RAND-36 vitality score (65.2
      vs. 66.8; regression coefficient (RC) -1.6 [95% confidence interval (CI) -2.6 to 
      0.5]; p=0.005) and a higher SFQ score (11.7 vs. 11.0; RC 0.6 [CI 0.2-1.0];
      p=0.004) than those with a TSH of 1.0-2.0 mIU/L. Those with a serum FT(4) of 18.5
      22 pmol/L reported fatigue more often (52.5% vs. 33.3%; relative risk (RR) 1.4
      [CI 1.0-1.9]; p=0.03), had a lower RAND-36 vitality score (61.7 vs. 66.6; RC -4.4
      [CI -8.1 to -0.6]; p=0.02) and a higher SFQ score (13.2 vs. 11.0; RC 1.9 [CI 0.4
      3.3]; p=0.01) than subjects with a FT(4) level of 11.5-15 pmol/L. In comparison
      to euthyroid subjects without known thyroid disease, euthyroid subjects with
      previously known thyroid disease reported fatigue more often (52.3% vs. 34.0%; RR
      1.3 [CI 1.0-1.5]; p=0.025), had a lower RAND-36 vitality score (61.4 vs. 66.3; RC
      -2.9 [CI -5.3 to -0.6]; p=0.015) and a higher SFQ score (13.7 vs. 11.1; RC 1.4
      [CI 0.5-2.3]; p=0.002). CONCLUSION: In euthyroid individuals without a history of
      thyroid disease, there is a modest relationship between thyroid function and
      fatigue with subjects having an apparently higher production of T(4) experiencing
      more fatigue. Subjects with a history of thyroid disease, but with normal TSH and
      FT(4) concentrations, experience more fatigue than the general population. The
      reasons for this are unclear, but subtle abnormalities in the dynamics of thyroid
      hormone secretion should be considered.

PMID- 22966869
TI  - Role of arginine 29 and glutamic acid 81 interactions in the conformational
      stability of human chloride intracellular channel 1.
AB  - The ion channel protein CLIC1 exists in both a soluble conformation in the
      cytoplasm and a membrane-bound conformation. The conformational stability of
      soluble CLIC1 demonstrates pH sensitivity which may be attributable to very
      specific residues that function as pH sensors. These sensors could be histidine
      or glutamate residues with pK(a) values that fall within the physiological pH
      range. The role of Glu81, a member of a topologically conserved buried salt
      bridge in CLIC1, as a pH sensor was investigated here. The mutants E81M, R29M,
      and E81M/R29M were designed to break the salt bridge between Glu81 and Arg29 and
      examine the effect of each member on the stability of the protein. Spectroscopic
      studies and the solved crystal structures indicated that the global structure of
      CLIC1 was not affected by the mutations. Urea-induced equilibrium unfolding
      unexpectedly showed E81M to stabilize CLIC1 at pH 7. This was due to stabilizing
      hydrophobic interactions with Met81 and a water-mediated compensatory H-bond
      between Met81 and Arg29. R29M and E81M/R29M destabilized CLIC1 at pH 7, and the
      unfolding transition changed from two-state to three-state, mimicking the wild
      type at pH 5.5. This observation points out the significance of the salt bridge
      in stabilizing the native state. The total unfolding free energy change of E81M
      CLIC1 does not change with pH, implying that Glu81 forms one of a network of pH
      sensor residues in CLIC1 responsible for destabilization of the native state.
      This allows detachment of the N-domain from the C-domain at low pH.

PMID- 22966870
TI  - The evolution of pigeon paramyxovirus type 1 (PPMV-1) in Great Britain: a
      molecular epidemiological study.
AB  - Newcastle disease (ND), caused by virulent strains of avian paramyxovirus type 1
      (APMV-1), is considered throughout the world as one of the most important animal
      diseases. For over three decades now, there has been a continuing panzootic
      caused by a variant virulent APMV-1 strain, so-called pigeon paramyxovirus type 1
      (PPMV-1), primarily in racing pigeons, which has also spread to wild birds and
      poultry. PPMV-1 isolations have been made in Great Britain every year since 1983.
      In this study, we have completed a comparative phylogenetic analysis based on a
      374 nucleotide section of the fusion protein gene of 63 isolates of PPMV-1 that
      were isolated over a 26-year period; 43 of these were sequenced for this study.
      Phylogenetic analysis of these sequences revealed that all were closely related
      and placed in the genetic sublineage 4b (VIb), subdivision 4biif. 

PMID- 22966872
TI  - AV nodal fat pad stimulation for rate control in atrial fibrillation and heart
      failure: a better solution?

PMID- 22966871
TI  - A perspective on progress and gaps in HIV prevention science.
AB  - In the past few years, the transdisciplinary field of HIV prevention has reached
      several milestones. Topically applied tenofovir gel provided significant
      protection from sexual transmission of HIV in a large-scale clinical trial and
      oral Truvada (emtricitabine/tenofovir disoproxil fumarate) was recently approved
      for preexposure prophylaxis (PrEP) following two successful clinical trials in
      men and women. These achievements are tempered by the disappointing results of
      other clinical trials, which highlight the complexities of prevention research.
      In this perspective, we discuss scientific and developmental gaps for topical
      chemoprophylaxis of the sexual transmission of HIV, which depends on the complex
      interactions between the pharmacokinetics and pharmacodynamics of drugs,
      formulation and delivery systems, anatomic site of transmission, and host mucosal
      immune defenses. Despite the considerable time and resources devoted to
      unraveling the initial steps in sexual transmission of HIV, current knowledge is
      based on animal models and human explanted tissue, which may not fully
      recapitulate what happens clinically. Understanding these events, including the
      role that sex hormones, semen, and mucosal secretions play in transmission, and
      the interplay between innate immunity, the mucosal environment, and drug efficacy
      is paramount. This drives some of the most pressing questions in the field.

PMID- 22966873
TI  - Synthesis of the reported structures for kealiinines B and C.
AB  - Syntheses of the reported structures of kealiinines B and C have been executed.
      An intermolecular electrophile-induced cyclization of a pendant arene on an ene
      guanidine affords the tetracyclic, oxidized naphthimidazole cores.

PMID- 22966874
TI  - New high-temperature Pb-catalyzed synthesis of inorganic nanotubes.
AB  - A new procedure for the synthesis of MoS(2) nanotubes is reported, and
      additionally demonstrated for MoSe(2), WS(2), and WSe(2). Highly concentrated
      sunlight creates continuous high temperatures, strong temperature gradients, and
      extended hot annealing regions, which, together with a metallic (Pb) catalyst,
      are conducive to the formation of different inorganic nanotubes. Structural
      characterization (including atomic resolution images) reveals a three-step
      reaction mechanism. In the first step, MoS(2) platelets react with water-air
      residues, decompose by intense solar irradiation, and are converted to molybdenum
      oxide. Subsequently, the hot annealing environment leads to the growth of Pb
      stabilized MoO(3-x) nanowhiskers. Shortly afterward, the surface of the MoO(3-x)
      starts to react with the sulfur vapor supplied by the decomposition of nearby
      MoS(2) platelets and becomes enveloped by MoS(2) layers. Finally, the molybdenum
      oxide core is gradually transformed into MoS(2) nanotubes. These findings augur
      well for similar syntheses of as yet unattained nanotubes from other metal
      chalcogenides.

PMID- 22966875
TI  - A qualitative analysis of communication between members of a hospital-based
      multidisciplinary lung cancer team.
AB  - The aim of the study was to explore how patient information is communicated
      between health professionals within a multidisciplinary hospital-based lung
      cancer team and to identify mechanisms to improve these communications. A
      qualitative method was employed using semi-structured in-depth interviews with a
      representative sample (n = 22) of members of a multidisciplinary hospital-based
      lung cancer team including medical, nursing and allied health professionals.
      Analysis was undertaken using a thematic grounded theory approach to derive key
      themes to describe communication patterns within the team and how communication
      could be improved. Two themes with sub-themes were identified: (1)
      characteristics of communication between team members including the impact of
      role on direction of communications, and doctors' dominance in communications;
      and (2) channels of communication including, preference for face-to-face and the
      suboptimal roles of the Multidisciplinary Team Meeting and the hospital medical
      record as mediums for communication. Traditional influences of role delineation
      and the dominance of doctors were found to impact on communication within the
      multidisciplinary hospital-based lung cancer team. Existing guidelines on
      implementation of multidisciplinary cancer care fail to address barriers to
      effective team communication. The paper-based medical record does not support
      team communications and alternative electronic solutions need to be used.

PMID- 22966876
TI  - Interaction of atrial natriuretic peptide and ouabain in the myocardium.
AB  - Natriuretic peptides and digitalis-like compounds serve as regulators of
      homeostasis, including control of volume expansion and blood pressure. The aim of
      the present study was to explore possible interactions between atrial natriuretic
      peptide (ANP) and ouabain in the heart. ANP (1 nmol/L) had no effect in papillary
      muscle preparations from guinea pigs. Ouabain (1 umol/L) induced positive
      inotropic effect. The addition of ANP prior to ouabain resulted in a significant
      decrease in the ouabain-induced positive inotropic effect, manifested as an
      attenuated increase in twitch maximal upward force slope and resting muscular
      tension. In addition, ANP caused an increase in Na+-K+-ATPase activity in heart
      microsomal preparations. The effect of ouabain on Na+-K+-ATPase activity was
      shown in a biphasic manner. Ouabain (0.01-1 nmol/L) had a small but significant
      increase on pump activity, but higher doses of ouabain inhibited activity. ANP
      attenuated ouabain-induced Na+-K+-ATPase activity. Furthermore, ouabain (50
      nmol/L) or ANP (10 nmol/L) alone induced Akt activation in cardiomyocytes.
      However, ANP blocked ouabain-induced Akt activation. These results point to the
      existence of interactions between ANP and ouabain on Na+-K+-ATPase signaling and
      function in the heart, which may be mediated by regulation of Na+-K+-ATPase
      activity and (or) signal transduction mechanisms.

PMID- 22966877
TI  - Selection of rituximab dosage in chronic lymphocytic leukemia: where is the
      evidence?
AB  - Rituximab prolongs survival in many CD20-expressing B- lymphoid malignancies. In
      non-Hodgkin lymphoma (NHL), a large number of clinical studies have established
      the 375 mg/m(2) dose of rituximab as standard. In chronic lymphocytic leukemia
      (CLL), response rates to single-agent rituximab at the NHL dose were low, but the
      use of higher doses or more frequent dosing have led to improved response rates,
      suggesting that a higher dose may be required. This led to the empiric decision
      to adopt rituximab at 500 mg/m(2) in combination with fludarabine and
      cyclophosphamide (FC) in phase II and III trials in CLL. The final result was the
      approval of rituximab at 500 mg/m(2) for treatment of CLL, in combination with
      FC. There is, however, preclinical evidence that full saturation of CD20
      molecules may not be required to achieve chemosensitization in cancer cells, and
      it remains possible that the approved dose of 500 mg/m(2) is higher than what is
      required to achieve maximal in vivo synergy. Nevertheless, all of the randomized
      evidence for superiority of rituximab plus chemotherapy over chemotherapy alone
      comes from studies using the 500 mg/m(2) dose.

PMID- 22966879
TI  - Is there clinical utility to IL28B genotype testing in the treatment of chronic
      hepatitis C virus infection?

PMID- 22966878
TI  - Vitamin D intake is negatively associated with promoter methylation of the Wnt
      antagonist gene DKK1 in a large group of colorectal cancer patients.
AB  - Diet and lifestyle influence colorectal cancer (CRC) risk but the molecular
      events that mediate these effects are poorly characterized. Several dietary and
      lifestyle factors can modulate DNA methylation suggesting that they may influence
      CRC risk through epigenetic regulation of cancer-related genes. The Wnt
      regulatory genes DKK1 and Wnt5a are important contributors to colonic
      carcinogenesis and are often silenced by promoter hypermethylation in CRC;
      however, the dietary contributions to these events have not been explored. To
      investigate the link between dietary/lifestyle factors and epigenetic regulation
      of these Wnt signaling genes, we assessed promoter methylation of these genes in
      a large cohort of Canadian CRC patients from Ontario (n = 549) and Newfoundland
      (n = 443) and examined associations to dietary/lifestyle factors implicated in
      CRC risk and/or DNA methylation including intake of vitamins, fats, cholesterol,
      fiber, and alcohol as well as body mass index (BMI), and smoking status. Several
      factors were associated with methylation status including alcohol intake, BMI,
      and cigarette smoking. Most significantly, however, dietary vitamin D intake was
      strongly negatively associated with DKK1 methylation in Newfoundland (P = 0.001)
      and a similar trend was observed in Ontario. These results suggest that vitamin D
      and other dietary/lifestyle factors may alter CRC risk by mediating extracellular
      Wnt inhibition.

PMID- 22966880
TI  - The miRNA-drug resistance connection: a new era of personalized medicine using
      noncoding RNA begins.

PMID- 22966882
TI  - KCNQ1 variants and response to repaglinide treatment in patients with Type 2
      diabetes.

PMID- 22966883
TI  - Institutional profile: pharmacogenomics research at Newcastle University.

PMID- 22966884
TI  - Effects of polymorphisms in six candidate genes on phenytoin maintenance therapy
      in Han Chinese patients.
AB  - AIM: The present study aimed to investigate the associations between variants in
      pharmacokinetic- and pharmacodynamic-related genes with the dosages,
      concentrations and concentration-dose ratios (CDRs) of phenytoin (PHT). METHODS &
      RESULTS: Eleven genetic polymorphisms in the six candidate genes were detected in
      269 epileptic patients under maintenance PHT monotherapy by real-time PCR and PCR
      RFLP. Results of a bivariate analysis demonstrated that among tested
      polymorphisms, carriers of the variant CYP2C9*3 tended to require significantly
      lower maintenance PHT dosages than wild-type carriers (p < 0.0001); on the other
      hand, carriers of the variants CYP2C9*3 or CYP2C19*3 revealed significantly
      higher CDRs than wild-type carriers (p < 0.004). In a further multivariate
      analysis, variants in SCN1A, CYP2C9, CYP2C19 and ABCB1 genes were significantly
      associated with CDRs of PHT under adjustment of age, gender and epilepsy
      classifications (adjusted r(2) = 20.07%). CONCLUSION: The results of present
      study indicated that polygenic analysis may provide useful information in PHT
      therapy optimization.

PMID- 22966885
TI  - Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R:
      a microarray study.
AB  - AIM: The adrenolytic agent mitotane is widely used in the treatment of
      adrenocortical cancer; however, its mechanism of action is poorly elucidated. We
      have studied mitotane-induced mRNA expression changes in the NCI-H295R
      adrenocortical cancer cell line. MATERIALS & METHODS: Cell viability and hormone
      assays were used to select the optimal mitotane concentration effectively
      inhibiting hormone secretion without affecting cell viability. RNA isolated from
      cultures treated for 48 and 72 h was subjected to Agilent 4*44K microarray
      platforms. Microarray results were validated by quantitative reverse
      transcription PCR. RESULTS: Altogether, 117 significantly differentially
      expressed genes were detected at 48 h and 72 h (p < 0.05) in mitotane-treated
      samples relative to controls. Three significantly underexpressed genes involved
      in steroid hormone biosynthesis (HSD3B1, HSD3B2 and CYP21A2) and four
      significantly overexpressed genes (GDF15, ALDH1L2, TRIB3 and SERPINE2) have been
      validated. CONCLUSION: Gene-expression changes might be involved in the adrenal
      action of mitotane and in the inhibition of hormone secretion.

PMID- 22966886
TI  - G894T polymorphism of eNOS gene is a predictor of response to combination of
      inhaled corticosteroids with long-lasting beta2-agonists in asthmatic children.
AB  - AIM: Nitric oxide synthase enzymes have an important role in airway inflammation
      in asthmatic children. In the present study, the association between eNOS gene
      polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting
      beta(2)-agonists (LABAs) was investigated. PATIENTS & METHODS: A total of 81
      asthmatic children treated with ICS plus LABAs and 96 healthy controls were
      genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the
      PCR-RFLP method. RESULTS: G894T and -786T/C polymorphisms were not associated
      with asthma susceptibility. Among asthmatic children, 894TT carriers had higher
      change in forced expiratory volume in 1 s (FEV(1)) in response to ICS plus LABAs
      compared with 894GG carriers (21.9 +/- 3.8 vs 1.6 +/- 1.9%; p < 0.001). In
      responders (FEV(1) change >=7.5%), frequency of 894TT genotype was significantly
      higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C
      polymorphism alone were less clear and in most cases nonsignificant. CONCLUSION:
      The G894T polymorphism was associated with response to ICS and may serve as a
      useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic
      children.

PMID- 22966887
TI  - Epigenetic-dependent regulation of drug transport and metabolism: an update.
AB  - The pharmacokinetics of a drug are subject to large interindividual variability,
      which can result in lack of response or adverse drug reactions. In addition to
      genetic polymorphisms and drug interactions, key genes involved in the metabolism
      and transport of drugs are demonstrated to have epigenetic influences that can
      potentially affect interindividual variability in drug response. Emerging studies
      have focused on the importance of DNA methylation for ADME gene expression and
      for drug action and resistance, particularly in cancer. However, the epigenetic
      and ncRNA-dependent regulation of these genes, as well as the pharmacological
      consequences, is in need of greater attention. In the current review we provide
      an update of epigenetic and ncRNA-dependent regulation of ADME genes.

PMID- 22966889
TI  - Cost-effectiveness of pharmacogenetics in anticoagulation: international
      differences in healthcare systems and costs.
AB  - Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy
      of dosing during the initiation of anticoagulation with vitamin K antagonists
      (coumarin derivatives). The anticipated degree of improvement in the safety of
      anticoagulation with coumarins through genotyping may vary depending on the
      quality of patient care, which varies both with and among countries. The
      management and the cost of anticoagulant care can therefore influence the cost
      effectiveness of genotyping within any given country. In this article, we provide
      an overview of the cost-effectiveness of pharmacogenetics-guided dosing of
      coumarin derivatives. We describe the organization of anticoagulant care in the
      UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided
      dosing algorithm is currently being investigated as part of the EU-PACT trial. We
      also explore the costs of anticoagulant care for the treatment of atrial
      fibrillation in these countries.

PMID- 22966890
TI  - The current and future state of pharmacogenomics medical education in the USA.
AB  - Healthcare professionals (e.g., physicians, physician assistants, pharmacists,
      nurses and genetic counselors) believe pharmacogenomics (PGx) is essential to
      personalized medicine; however, they still lack confidence prescribing, dosing,
      interacting with other healthcare professionals and counseling patients with
      regard to PGx. This is due to the inadequate incorporation of PGx content into
      professional curricula. Compared with other health professions, Doctor of
      Pharmacy programs have integrated more PGx content. Unlike other healthcare
      professionals, pharmacists have extensive training in pharmacology, drug
      selection, drug dosage, drug-drug interactions and are uniquely accessible to
      patients. We suggest pharmacists are the best poised to facilitate incorporating
      PGx into therapeutic decision-making. Based on our experience as undergraduate
      and pharmacy PGx educators, we further reflect on our experience educating future
      healthcare professionals on PGx.

PMID- 22966891
TI  - Association of DHODH haplotype variants and response to leflunomide treatment in
      rheumatoid arthritis.
AB  - AIM: Leflunomide is a disease-modifying antirheumatic drug used in the treatment
      of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has
      potentially serious side effects, targeting only those most likely to benefit
      would address a clinical need. We aimed to determine whether variations in the
      gene encoding DHODH, the molecular target of leflunomide, might include
      biomarkers that could be used to rationalize provision of this drug. MATERIALS &
      METHODS: We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with
      rheumatoid arthritis treated with leflunomide. Clinical response was determined
      by assessing the change in 28 joint disease activity score over the first 3
      months of treatment. RESULTS & CONCLUSION: Carriage of a six-marker DHODH
      haplotype was associated with a reduced treatment response (p = 0.008). This
      suggests that a functional variant in strong linkage disequilibrium with this
      haplotype may predispose to reduced leflunomide efficacy.

PMID- 22966888
TI  - Integrative systems biology approaches in asthma pharmacogenomics.
AB  - In order to improve therapeutic outcomes, there is a tremendous need to identify
      patients who are likely to respond to a given asthma treatment. Pharmacogenomic
      studies have explained a portion of the variability in drug response and provided
      an increasing list of candidate genes and SNPs. However, as phenotypic variation
      arises from a network of complex interactions among genetic and environmental
      factors, rather than individual genes or SNPs, a multidisciplinary, systems-level
      approach is required in order to understand the inter-relationships among these
      factors. Systems biology, which seeks to capture interactions between genetic
      factors and other variables, offers a promising approach to improved therapeutic
      outcomes in asthma. This aritcle will review and update progress in the
      pharmacogenomics of asthma and then discuss the application of systems biology
      approaches to asthma pharmacogenomics.

PMID- 22966893
TI  - Wheezing and asthma are independent risk factors for increased sickle cell
      disease morbidity.
AB  - To assess the associations between a doctor diagnosis of asthma and wheezing
      (independent of a diagnosis of asthma) with sickle cell disease (SCD) morbidity,
      we conducted a retrospective review of Emergency Department (ED) visits to the
      Mount Sinai Medical Center for SCD between 1 January 2007 and 1 January 2011.
      Outcomes were ED visits for pain and acute chest syndrome. The cohort included
      262 individuals, median age 23.8 years, (range: 6 months to 67.5 years). At least
      one episode of wheezing recorded on a physical examination was present in 18.7%
      (49 of 262). Asthma and wheezing did not overlap completely, 53.1% of patients
      with wheezing did not carry a diagnosis of asthma. Wheezing was associated with a
      118% increase in ED visits for pain (95% confidence interval [CI]: 56-205%) and a
      158% increase in ED visits for acute chest syndrome (95% CI: 11-498%). A
      diagnosis of asthma was associated with a 44% increase in ED utilization for pain
      (95% CI: 2-104%) and no increase in ED utilization for acute chest syndrome (rate
      ratio 1.00, 95%CI 0.41-2.47). In conclusion, asthma and wheezing are independent
      risk factors for increased painful episodes in individuals with SCD. Only
      wheezing was associated with more acute chest syndrome.

PMID- 22966894
TI  - Implementation of shared decision making by physician training to optimise
      hypertension treatment. Study protocol of a cluster-RCT.
AB  - BACKGROUND: Hypertension is one of the key factors causing cardiovascular
      diseases which make up the most frequent cause of death in industrialised
      nations. However about 60% of hypertensive patients in Germany treated with
      antihypertensives do not reach the recommended target blood pressure. The
      involvement of patients in medical decision making fulfils not only an ethical
      imperative but, furthermore, has the potential of higher treatment success. One
      concept to enhance the active role of patients is shared decision making. Until
      now there exists little information on the effects of shared decision making
      trainings for general practitioners on patient participation and on lowering
      blood pressure in hypertensive patients. METHODS/DESIGN: In a cluster-randomised
      controlled trial 1800 patients receiving antihypertensives will be screened with
      24 h ambulatory blood pressure monitoring in their general practitioners'
      practices. Only patients who have not reached their blood pressure target
      (approximately 1200) will remain in the study (T1 - T3). General practitioners of
      the intervention group will take part in a shared decision making-training after
      baseline assessment (T0). General practitioners of the control group will treat
      their patients as usual. Primary endpoints are change of systolic blood pressure
      and change of patients' perceived participation. Secondary endpoints are changes
      of diastolic blood pressure, knowledge, medical adherence and cardiovascular
      risk. Data analysis will be performed with mixed effects models. DISCUSSION: The
      hypothesis underlying this study is that shared decision making, realised by a
      shared decision making training for general practitioners, activates patients,
      facilitates patients' empowerment and contributes to a better hypertension
      control. This study is the first one that tests this hypothesis with a (cluster-)
      randomised trial and a large sample size.

PMID- 22966895
TI  - Determining alpha-helical and beta-sheet secondary structures via pulsed electron
      spin resonance spectroscopy.
AB  - A new method has been developed to determine alpha-helical and beta-sheet
      secondary structural components of aqueous and membrane-bound proteins using
      pulsed electron paramagnetic resonance (EPR) spectroscopy. The three-pulse
      electron spin echo envelope modulation (ESEEM) technique was used to detect
      weakly coupled (2)H-labeled nuclei on side chains in the proximity of a
      strategically placed nitroxide spin-label up to 8 A away. Changes in the ESEEM
      spectra for different samples correlate directly to periodic structural
      differences between alpha-helical and beta-sheet motifs. These distinct trends
      were demonstrated with alpha-helical (M2delta subunit of the acetylcholine
      receptor) and beta-sheet (ubiquitin) peptides in biologically relevant sample
      environments.

PMID- 22966896
TI  - Fabrication of carboxylated silicon nitride sensor chips for  detection of
      antigen-antibody reaction using microfluidic reflectometric interference
      spectroscopy.
AB  - In this study, we report label-free detection of alpha-fetoprotein (AFP), which
      has been used as a biomarker for hepatocellular carcinoma, by a microfluidic
      reflectometric interference spectroscopy (RIfS) system adopting a simple halogen
      light source and an inexpensive silicon-based sensor chip. Introduction of
      carboxy groups on a silicon nitride sensor chip to immobilize anti-AFP monoclonal
      antibody (anti-AFP) was carried out simply by immersion in aqueous solution
      containing triethoxysilylpropylmaleamic acid bearing a carboxy group and a
      silanol group. The RIfS system with the anti-AFP-immobilized sensor chip was
      found to give a reversible response through 100 on/off cycles using a
      regeneration buffer with high reproducibility (coefficient of variation (CV) =
      5.7%). The limit of detection (LOD) of AFP was 100 ng mL(-1), and the measurement
      range spanned 3 orders of magnitude. Furthermore, the sensor chip showed no cross
      reactivity with human serum albumin, Immunoglobulin G, transferrin, or fibrinogen
      at 100 MUg mL(-1) without the use of blocking reagents such as bovine serum
      albumin. Consequently, the proposed RIfS system is a potentially effective tool
      for biomarker detection and in vitro diagnostics.

PMID- 22966897
TI  - Molecular autopsy for sudden unexplained death? Time to discuss pros and cons.

PMID- 22966899
TI  - The mean platelet volume is positively correlated with serum thyrotropin
      concentrations in a population of healthy subjects and subjects with unsuspected
      subclinical hypothyroidism.
AB  - BACKGROUND: A possible prothrombotic effect of elevated thyrotropin (TSH) has
      been suggested. The mean platelet volume (MPV), which is used to measure the
      platelet size, can reflect platelet activity. Although limited and inconsistent
      data regarding the effects of thyroid function on the MPV are available from
      small-scale case-control studies, no study has been based on a general
      population, particularly in euthyroid states. The objective of the present study
      was to determine whether there is an association between the MPV and serum TSH
      concentrations in an apparently healthy Korean population without overt thyroid
      disease, but including subjects with unsuspected subclinical hypothyroidism
      (SCH). METHODS: We retrospectively studied 6893 asymptomatic Korean adults who
      were 20 years of age or older and who underwent voluntary regular health check
      ups at the Health Promotion Center of Chosun University Hospital. The subjects
      who met the inclusion and exclusion criteria were subdivided into four groups,
      such as tertile groups for the TSH reference range and an SCH (TSH >=4 MUIU/mL
      with a normal free T4 concentration) group according to the TSH level. We
      compared the mean values of the MPVs among the groups. Multivariate logistic
      regression analyses were used to identify associations between the highest
      tertile of the MPV and the TSH subgroups. RESULTS: The mean level of the MPV in
      all study subjects was 8.12+/-0.75 femtoliters (fL), and the mean value of the
      MPV was significantly different in each group. The mean MPV in SCH was
      significantly higher compared with those of the first tertile (T1) and second
      tertile (T2). Moreover, the mean MPV increased statistical significantly by
      increasing tertiles of the TSH concentration and was highest in SCH (T1, 8.08+/
      0.81 fL; T2, 8.09+/-0.62 fL; T3, 8.13+/-0.77 fL; SCH, 8.21+/-0.81 fL; p for
      trend=0.012). After adjusting for risk factors associated with increasing MPVs
      and platelet counts, SCH was independently associated with the highest tertile of
      the MPV (all subjects, odds radio (OR) 1.58 [95% confidence interval (CI) 1.19
      2.09]; men, OR 1.70 [CI 1.10-2.64]; women, OR 1.55 [CI 1.06-2.26]). CONCLUSIONS:
      The MPV was positively correlated with the TSH level. SCH is an independently
      associated factor with the highest tertile of MPV in a general Korean population.
      We propose that the MPV may contribute to the prothrombotic condition that is
      associated with SCH and perhaps even in putative euthyroid states where the TSH
      level is the higher part of the normal range.

PMID- 22966898
TI  - Biology of mucosally transmitted sexual infection-translating the basic science
      into novel HIV intervention: a workshop summary.
AB  - A group of over 200 international scientists came together on April 15 in Sydney,
      Australia just before the 2012 International Microbicides Conference as a part of
      a workshop to address the basic concepts and factors that modulate HIV infection
      at the mucosal surface. The meeting focused on defining the interaction between
      virus, prevailing host physiology, microbiota, and innate and adaptive immune
      responses and how they combine to impact the outcome at the moment of potential
      viral transmission. Speakers examined the biology of HIV entry during
      transmission, innate and natural antiviral mechanisms at the mucosa, microbicide
      efficacy, pharmacokinetic, and pharmacodynamics, animal models, and opportunities
      for combining HIV prevention strategies. Other viral infection models both in
      vivo and in vitro were considered for the insights they provided into HIV
      transmission events. The workshop raised important questions that we need to
      answer to further our basic understanding of host and viral factors influencing
      HIV transmission to inform the development of novel prevention strategies.

PMID- 22966900
TI  - Utility of urinary aldosterone measurement in quantitating RAAS activation.

PMID- 22966902
TI  - Toward the synthesis of wafer-scale single-crystal graphene on copper foils.
AB  - In this research, we constructed a controlled chamber pressure CVD (CP-CVD)
      system to manipulate graphene's domain sizes and shapes. Using this system, we
      synthesized large (~4.5 mm(2)) single-crystal hexagonal monolayer graphene
      domains on commercial polycrystalline Cu foils (99.8% purity), indicating its
      potential feasibility on a large scale at low cost. The as-synthesized graphene
      had a mobility of positive charge carriers of ~11,000 cm(2) V(-1) s(-1) on a
      SiO(2)/Si substrate at room temperature, suggesting its comparable quality to
      that of exfoliated graphene. The growth mechanism of Cu-based graphene was
      explored by studying the influence of varied growth parameters on graphene domain
      sizes. Cu pretreatments, electrochemical polishing, and high-pressure annealing
      are shown to be critical for suppressing graphene nucleation site density. A
      pressure of 108 Torr was the optimal chamber pressure for the synthesis of large
      single-crystal monolayer graphene. The synthesis of one graphene seed was
      achieved on centimeter-sized Cu foils by optimizing the flow rate ratio of
      H(2)/CH(4). This work should provide clear guidelines for the large-scale
      synthesis of wafer-scale single-crystal graphene, which is essential for the
      optimized graphene device fabrication.

PMID- 22966903
TI  - School environment as predictor of teacher sick leave: data-linked prospective
      cohort study.
AB  - BACKGROUND: Poor indoor air quality (IAQ) and psychosocial problems are common in
      schools worldwide, yet longitudinal research on the issue is scarce. We examined
      whether the level of or a change in pupil-reported school environment (IAQ,
      school satisfaction, and bullying) predicts recorded sick leaves among teachers.
      METHODS: Changes in the school environment were assessed using pupil surveys at
      two time points (2001/02 and 2004/05) in 92 secondary schools in Finland.
      Variables indicating change were based on median values at baseline. We linked
      these data to individual-level records of teachers' (n = 1678) sick leaves in
      2001-02 and in 2004-05. RESULTS: Multilevel multinomial logistic regression
      models adjusted for baseline sick leave and covariates showed a decreased risk
      for short-term (one to three days) sick leaves among teachers working in schools
      with good perceived IAQ at both times (OR = 0.6, 95% CI: 0.5-0.9), and for those
      with a positive change in IAQ (OR = 0.6, 95% CI: 0.4-0.9), compared to teachers
      in schools where IAQ was constantly poor. Negative changes in pupil school
      satisfaction (OR = 1.8, 95% CI: 1.1-2.8) and bullying (OR = 1.5, 95% CI: 1.0-2.3)
      increased the risk for short-term leaves among teachers when compared to teachers
      in schools where the level of satisfaction and bullying had remained stable.
      School environment factors were not associated with long-term sick leaves.
      CONCLUSIONS: Good and improved IAQ are associated with decreased teacher
      absenteeism. While pupil-related psychosocial factors also contribute to sick
      leaves, no effect modification or mediation of psychosocial factors on the
      association between IAQ and sick leave was observed.

PMID- 22966904
TI  - Natural Bagaza virus infection in game birds in southern Spain.
AB  - In late summer 2010 a mosquito born flavivirus not previously reported in Europe
      called Bagaza virus (BAGV) caused high mortality in red-legged partridges
      (Alectoris rufa) and ring-necked pheasants (Phasianus colchicus). We studied
      clinical findings, lesions and viral antigen distribution in naturally BAGV
      infected game birds in order to understand the apparently higher impact on red
      legged partridges. The disease induced neurologic signs in the two galliform
      species and, to a lesser extent, in common wood pigeons (Columba palumbus). In
      red-legged partridges infection by BAGV caused severe haemosiderosis in the liver
      and spleen that was absent in pheasants and less evident in common wood pigeons.
      Also, BAGV antigen was present in vascular endothelium in multiple organs in red
      legged partridges, and in the spleen in common wood pigeons, while in ring-necked
      pheasants it was only detected in neurons and glial cells in the brain. These
      findings indicate tropism of BAGV for endothelial cells and a severe haemolytic
      process in red-legged partridges in addition to the central nervous lesions that
      were found in all three species.

PMID- 22966905
TI  - Three-dimensional power Doppler transanal ultrasonography, to monitor
      haemorrhoidal blood flow after Doppler-guided ALTA sclerosing therapy.
AB  - AIM: The study aimed to use power Doppler imaging (PDI) transanal ultrasonography
      to produce three-dimensional power Doppler angiography images of haemorrhoidal
      tissue and to monitor the effects of Doppler-guided aluminium potassium sulfate
      and tannic acid (DGALTA) sclerotherapy. METHOD: Ninety-six haemorrhoids in 43
      patients were examined using PDI transanal ultrasonography, and DGALTA
      sclerotherapy was performed from April 2011 to April 2012. DGALTA sclerotherapy
      was conducted using a four-step injection process with pulse wave Doppler
      ultrasound under perianal local anaesthesia. RESULTS: A three-dimensional power
      Doppler angiography image of the blood flow in haemorrhoidal tissue was produced
      using PDI transanal ultrasonography. The cross-sectional area of blood flow in
      the haemorrhoidal tissue (PDI area) significantly decreased after DGALTA
      sclerotherapy. The PDI areas in the preoperative state and 1 and 3 months after
      treatment were 0.35+/-0.27, 0.03+/-0.05 and 0.04+/-0.05 cm(2) (P<0.0001).
      CONCLUSION: A three-dimensional power Doppler angiography image of the
      haemorrhoidal tissue was technically possible and showed blood flow in the
      haemorrhoidal tissue to be significantly decreased after DGALTA sclerotherapy.

PMID- 22966906
TI  - Cancer incidence and survival (1997-2006) among adolescents and young adults in
      the north of Portugal.
AB  - Cancer is the first cause of natural death among young subjects. Population-based
      statistics are important to evaluate the burden of disease and the effectiveness
      of healthcare provision. We aimed to describe cancer incidence and survival among
      adolescents (15-19 years) and young adults (20-24 years) in the north of
      Portugal. Data on the cancers diagnosed between 1997 and 2006 were obtained from
      the Portuguese North Region Cancer Registry, and incidence rates were computed.
      Vital status was determined until December 2010. Survival was estimated using the
      Kaplan-Meier survival function. Trends on cancer incidence were assessed using
      the Joinpoint regression analysis. A total of 1223 cases were diagnosed: 441
      among adolescents and 782 among young adults. Overall incidence rate was 198.3
      per million adolescents [95% confidence interval (95% CI): 135.7-260.9] and 306.2
      per million young adults (95% CI: 262.3-350.0). The most frequent tumors were
      Hodgkin lymphoma (adolescents: 21.0%; young adults: 14.8%), thyroid carcinoma
      (adolescents: 11.5%; young adults: 16.2%), and germ cell tumors (adolescents:
      11.1%; young adults: 16.3%). Cancer incidence significantly increased among young
      adults [annual average percent change: 3.6%, (95% CI: 1.7-5.4)], while appears to
      vary randomly among adolescents. Overall five-year observed survival was 77.2%
      (95% CI: 72.9%-80.8%) among adolescents and 81.3% (95% CI: 78.4%-83.9%) among
      young adults, lower in males. In conclusion, cancer incidence among adolescents
      and young adults is higher in the north of Portugal than in other European
      countries, especially of thyroid tumors. Between 1997 and 2006, the incidence
      increased significantly in young adults.

PMID- 22966908
TI  - Meta-analysis: oral bisphosphonates and the risk of oesophageal cancer.
AB  - BACKGROUND: Bisphoshonates, which are used in the treatment and prevention of
      osteoporosis, have recently been implicated in the development of oesophageal
      cancer; however, studies report conflicting data. AIM: To conduct a meta-analysis
      of studies reporting on the association between bisphosphonates and oesophageal
      cancer to quantify the relationship. METHODS: A search was conducted through
      Medline, PubMed, Embase and Current Contents Connect to 2 August 2012. We
      calculated pooled odds ratios and 95% CIs using a random effects model for the
      risk of oesophageal cancer associated with exposure to bisphosphonates, as well
      as for the different periods of exposure. RESULTS: Seven studies, with 19 700
      oesophageal cancer cases, met our inclusion criteria. We found a positive
      relationship between exposure to bisphosphonates and oesophageal cancer, with an
      odds ratio (OR) of 1.74 with a 95% CI of 1.19-2.55. Heterogeneity was observed
      (I(2 ) = 85%, P < 0.001). Publication bias was not present. An increased risk of
      oesophageal cancer was also found in the group exposed to bisphosphonates for a
      longer period of time, compared with the group who experienced a shorter period
      of exposure (OR 2.32; 95% CI 1.57-3.43 vs. OR 1.35; 95% CI 0.77-2.39). An
      increased risk was associated with exposure to Etidronate (OR 1.58; 95% CI 1.12
      2.24), but not to Aledronate. CONCLUSIONS: Exposure to bisphosphonates may be
      associated with an increased risk of oesophageal cancer. More studies are needed
      to confirm the relationship.

PMID- 22966909
TI  - Co-proccessed excipients with enhanced direct compression functionality for
      improved tableting performance.
AB  - It is necessary to have excipients with excellent functional properties to
      compensate for the poor mechanical properties and low aqueous solubility of the
      emerging active ingredients. Therefore, around 80% of the current drugs are not
      suitable for direct compression and more advanced excipients are required.
      Further, conventional grades of excipients cannot accommodate the technologically
      advanced high speed rotary tablet presses which require a powder with excellent
      flow, good compressibility, compactibility, particle size distribution and
      homogeneity of the ingredients. Co-processed excipients have been created to
      enhance the functional properties of the excipients and reduce their drawbacks.
      Co-processing is defined as the combination of two or more excipients by a
      physical process. Co-processed excipients are adequate for direct compression
      since they become multifunctional and thus, their dilution potential is high
      eliminating the need for many excipients in a formulation. In some cases, they
      are able to hold up to 50% of the drug in a formulation rendering compacts of
      good tableting properties. This study describes and discusses the functionality
      enhancement of commercial and investigational excipients through co-processing.

PMID- 22966907
TI  - Integrin alphavbeta3 and CD44 pathways in metastatic prostate cancer cells
      support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-kappaB
      ligand signaling axis.
AB  - BACKGROUND: Bone loss and pathological fractures are common skeletal
      complications associated with androgen deprivation therapy and bone metastases in
      prostate cancer patients. We have previously demonstrated that prostate cancer
      cells secrete receptor activator of NF-kB ligand (RANKL), a protein essential for
      osteoclast differentiation and activation. However, the mechanism(s) by which
      RANKL is produced remains to be determined. The objective of this study is to
      gain insight into the molecular mechanisms controlling RANKL expression in
      metastatic prostate cancer cells. RESULTS: We show here that phosphorylation of
      Smad 5 by integrin alphavbeta3 and RUNX2 by CD44 signaling, respectively,
      regulates RANKL expression in human-derived PC3 prostate cancer cells isolated
      from bone metastasis. We found that RUNX2 intranuclear targeting is mediated by
      phosphorylation of Smad 5. Indeed, Smad5 knock-down via RNA interference and
      inhibition of Smad 5 phosphorylation by an alphav inhibitor reduced RUNX2 nuclear
      localization and RANKL expression. Similarly, knockdown of CD44 or RUNX2
      attenuated the expression of RANKL. As a result, conditioned media from these
      cells failed to support osteoclast differentiation in vitro. Immunohistochemistry
      analysis of tissue microarray sections containing primary prostatic tumor (grade2
      4) detected predominant localization of RUNX2 and phosphorylated Smad 5 in the
      nuclei. Immunoblotting analyses of nuclear lysates from prostate tumor tissue
      corroborate these observations. CONCLUSIONS: Collectively, we show that CD44
      signaling regulates phosphorylation of RUNX2. Localization of RUNX2 in the
      nucleus requires phosphorylation of Smad-5 by integrin alphavbeta3 signaling. Our
      results suggest possible integration of two different pathways in the expression
      of RANKL. These observations imply a novel mechanistic insight into the role of
      these proteins in bone loss associated with bone metastases in patients with
      prostate cancer.

PMID- 22966910
TI  - Creating awareness and facilitating cervical and breast cancer screening uptake
      through the use of a Community Health Worker: a pilot intervention study.
AB  - In South Africa, cervical cancer is the most common female cancer followed by
      breast cancer. Despite the high incidence of these cancers, population-based
      screening is limited to cervical screening available at primary health clinics.
      Cervical screening uptake is, however, low. In 2009 a new cancer prevention
      initiative was launched in a specific resource poor community in Tshwane, South
      Africa. The low cervical screening uptake as well as a potentially low breast
      screening uptake could have resulted in the failure of this initiative. The
      purpose of the study was to develop and pilot test an intervention to address
      this risk. A Community Health Worker was trained and tasked to raise awareness of
      cervical and breast cancer and motivate women to take up screening. The
      intervention was assessed in terms of three outcomes: screening uptake, awareness
      and the value of the Community Health Worker. Despite the fact that the Community
      Health Worker's role was valued, screening uptake was disappointing and the level
      of awareness remained low. Unfortunately this intervention failed and once again
      we are left with the challenge of improving screening uptake.

PMID- 22966911
TI  - Effects of selected phytoestrogens and their mixtures on the function of the
      thyroid hormone and the aryl hydrocarbon receptor.
AB  - Phytoestrogens (PEs) are natural plant components, which can induce biologic
      responses in vertebrates by mimicking or blocking the actions of natural hormones
      or influencing the hormone production in the body. This study investigated the
      effect of different mixtures composed of food-relevant PEs on the thyroid hormone
      (TH) system assessing the proliferation of the 3,3',5-triiodi-L-thryonine (T3)
      dependent rat pituitary GH3 cells using the T-screen assay, and the effect on the
      aryl hydrocarbon receptor (AhR) transactivation using an AhR-luciferase reporter
      gene assay. Most tested PEs and their mixtures showed effect on both the TH and
      AhR system. Single isoflavonoid metabolites and their mixture and coumestrol
      induced GH3 cell growth and AhR transactivity dose-dependently. Isoflavonoid
      metabolites elicited an additive effect on the T3-dependent GH3 cell growth, and
      a synergistic effect on the AhR transactivity. In conclusion, nutrition-relevant
      PEs, alone and in mixture may possess endocrine-disrupting potential by
      interfering with TH and AhR functions, which need to be considered when assessing
      the effects on human health.

PMID- 22966912
TI  - Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid via
      competitive binary/ternary hydrogen-bonded complexes with 4-benzamidoprolinol.
AB  - Circular dichroism (CD) spectral examinations at various host/guest ratios
      revealed that 2-anthracenecarboxylic acid (AC) forms not only 1:1 but also novel
      2:1 hydrogen-bonded/pi-stacked complexes with a chiral 4-benzamidoprolinol
      template (TKS159). The 2:1 complexation is a minor process but causes significant
      CD spectral changes as a consequence of the exciton coupling interaction of two
      AC chromophores and greatly accelerates the head-to-head photocyclodimerization
      to significantly affect the stereochemical outcomes.

PMID- 22966913
TI  - CD30 expression in acute myeloid leukemia is associated with FLT3-internal tandem
      duplication mutation and leukocytosis.

PMID- 22966915
TI  - Children from immigrant families: introduction to the special section.

PMID- 22966916
TI  - Discrimination, ethnic identity, and academic outcomes of Mexican immigrant
      children: the importance of school context.
AB  - This study examined ethnic identity, perceptions of discrimination, and academic
      attitudes and performance of primarily first- and second-generation Mexican
      immigrant children living in a predominantly White community (N=204, 19 schools,
      mean age=9years). The study also examined schools' promotion of multiculturalism
      and teachers' attitudes about the value of diversity in predicting immigrant
      youth's attitudes and experiences. Results indicated that Latino immigrant
      children in this White community held positive and important ethnic identities
      and perceived low overall rates of discrimination. As expected, however, school
      and teacher characteristics were important in predicting children's perceptions
      of discrimination and ethnic identity, and moderated whether perceptions of
      discrimination and ethnic identity were related to attitudes about school and
      academic performance.

PMID- 22966917
TI  - Tridimensional acculturation and adaptation among Jamaican adolescent-mother
      dyads in the United States.
AB  - A bidimensional acculturation framework cannot account for multiple destination
      cultures within contemporary settlement societies. A tridimensional model is
      proposed and tested among Jamaican adolescent-mother dyads in the United States
      compared to Jamaican Islander, European American, African American, and other
      Black and non-Black U.S. immigrant dyads (473 dyads, M adolescent age = 14
      years). Jamaican immigrants evidence tridimensional acculturation, orienting
      toward Jamaican, African American, and European American cultures. Integration is
      favored (70%), particularly tricultural integration; moreover, Jamaican and other
      Black U.S. immigrants are more oriented toward African American than European
      American culture. Jamaican immigrant youth adapt at least as well as nonimmigrant
      peers in Jamaica and the United States. However, assimilated adolescents,
      particularly first generation immigrants, have worse sociocultural adaptation
      than integrated and separated adolescents.

PMID- 22966918
TI  - Health and medical care among the children of immigrants.
AB  - Using data spanning 1996-2009 from multiple panels of the Survey of Income and
      Program Participation, this study investigates children's (average age 8.5 years)
      physical health, dental visits, and doctor contact among low-income children
      (n=46,148) in immigrant versus native households. Immigrant households are
      further distinguished by household citizenship and immigration status. The
      findings show that children residing in households with non-naturalized citizen
      parents, particularly those with a nonpermanent resident parent, experience worse
      health and less access to care even when controlling for important demographic,
      socioeconomic, and health insurance variables.

PMID- 22966919
TI  - Immigrant-native differences in child health: does maternal education narrow or
      widen the gap?
AB  - Abundant U.S. research documents an "immigrant advantage" in children's physical
      health. This article extends consideration to the United Kingdom, permitting
      examination of a broader group of immigrants from disparate regions of the world
      and different socioeconomic backgrounds. Drawing on birth cohort data (ages 0-5)
      from both countries (n=4,139 and n=13,381), the analysis considers whether the
      children of immigrants have a physical and mental health advantage around the
      beginning of elementary school, and whether advantage is more pronounced among
      low-educated populations. Findings indicate that the children of immigrants are
      not uniformly healthier than those in native-born families. Rather, there is
      heterogeneity in the immigrant advantage across outcomes, and evidence of both
      greater advantage and disadvantage among children in low-educated immigrant
      families.

PMID- 22966920
TI  - Family functioning and early learning practices in immigrant homes.
AB  - Poverty-related developmental-risk theories dominate accounts of uneven levels of
      household functioning and effects on children. But immigrant parents may sustain
      norms and practices-stemming from heritage culture, selective migration, and
      social support-that buffer economic exigencies. Comparable levels of social
      emotional functioning in homes of foreign-born Latino mothers were observed
      relative to native-born Whites, despite sharp social-class disparities, but
      learning activities were much weaker, drawing on a national sample of mothers
      with children aging from 9 to 48months (n=5,300). Asian-heritage mothers reported
      weaker social functioning-greater martial conflict and depression-yet stronger
      learning practices. Mothers' migration history, ethnicity, and social support
      helped to explain levels of functioning, after taking into account multiple
      indicators of class and poverty.

PMID- 22966922
TI  - Academic achievement of legal immigrants' children: the roles of parents' pre-
      and postmigration characteristics in origin-group differences.
AB  - Using data from the New Immigrant Survey, a study based on a nationally
      representative sample of legal immigrants, the present study extends prior
      research on the academic outcomes of immigrants' children by examining the roles
      of pre- and postmigration parental characteristics and the home environment. An
      analysis of 2,147 children aged 6-12 shows that parents' premigration education
      is more strongly associated with children's academic achievement than any other
      pre- or postmigration attribute. Premigration parental attributes account for the
      test score disadvantage of Mexican-origin children of legal immigrants, relative
      to their non-Latino counterparts. The findings reveal continuities and
      discontinuities in parental socioeconomic status and demonstrate that what
      parents bring to the United States and their experiences after arrival influence
      children's academic achievement.

PMID- 22966923
TI  - Educational achievement of immigrant adolescents in Spain: do gender and region
      of origin matter?
AB  - This study explores the educational achievement of immigrant youth in Spain
      employing data from 3 waves of the Longitudinal Study of Families and Childhood
      (Panel de Families i Infancia), a representative sample of children in Catalonia
      first interviewed at ages 13-16 in 2006 (N = 2,710). Results suggest consistent
      disadvantage in achievement among first-generation students. Differences in
      achievement between the second and third generations are apparent in bivariate
      analyses, but are explained by observable characteristics in multivariate
      analyses. Gender-specific analyses uncover a large achievement gap between first
      generation girls and their third-generation counterparts, but no equivalent gap
      for boys. Region-of-origin differences are modest, with the exception of Latin
      American adolescents who exhibit the lowest educational outcomes. The
      significance of perceptions about school on achievement are discussed.

PMID- 22966921
TI  - Migration timing and parenting practices: contributions to social development in
      preschoolers with foreign-born and native-born mothers.
AB  - Little is known about how key aspects of parental migration or childrearing
      history affect social development across children from immigrant families.
      Relying on data on approximately 6,400 children from the Early Childhood
      Longitudinal Study-Birth Cohort, analyses assessed the role of mother's age at
      migration on children's social development in the United States (sociability and
      problem behaviors). Consistent with models of divergent adaptation and
      assimilation, the relation between age at arrival and children's social
      development is not linear. Parenting practices, observed when children were
      approximately 24months of age, partially mediated the relation between mother's
      age at arrival and children's social development reported at approximate age
      48months, particularly in the case of mothers who arrived as adults.

PMID- 22966924
TI  - Multiple identities and religious transmission: a study among Moroccan-Dutch
      Muslim adolescents and their parents.
AB  - This study investigates the relation between religious group identification and
      ethnic and national identity among Moroccan-Dutch Muslim adolescents (11-18
      years) and their parents (n=369). Compared to their parents, adolescents showed
      higher national identification and lower religious and ethnic group
      identification. However, for adolescents and their parents, there were similar
      positive relations between Muslim and ethnic identifications, and both
      identifications were negatively related to Dutch identification. For early
      adolescents, parent's religious group identification was strongly related to
      their religious identification and ethnic and national identifications. These
      associations were not significant for middle adolescents. It is concluded that
      research on children from immigrant Muslim families should not only focus on
      ethnicity but on religious identity in particular.

PMID- 22966925
TI  - The development of young children of immigrants in Australia, Canada, the United
      kingdom, and the United States.
AB  - In spite of important differences in some of the resources immigrant parents have
      to invest in their children, and in immigrant selection rules and settlement
      policies, there are significant similarities in the relative positions of 4- and
      5-year-old children of immigrants in Australia, Canada, the United Kingdom, and
      the United States. Children of immigrants underperform their counterparts with
      native-born parents in vocabulary tests, particularly if a language other than
      the official language is spoken at home, but are not generally disadvantaged in
      nonverbal cognitive domains, nor are there notable behavioral differences. These
      findings suggest that the cross-country differences in cognitive outcomes during
      the teen years documented in the existing literature are much less evident during
      the early years.

PMID- 22966926
TI  - New destinations, new trajectories? The educational progress of Hispanic youth in
      North Carolina.
AB  - Since 1990, Latin American immigrants to the United States have dispersed beyond
      traditional gateway regions to a number of "new destinations." Both theory and
      past empirical evidence provide mixed guidance as to whether the children of
      these immigrants are adversely affected by residing in a nontraditional
      destination. This study uses administrative public school data to study over
      2,800 8- to 18-year-old Hispanic youth in one new destination, North Carolina.
      Conditional on third-grade socioeconomic indicators, Hispanic youth who arrive by
      age 9 and remain enrolled in North Carolina public schools close achievement gaps
      with socioeconomically similar White students by sixth grade and exhibit
      significantly lower high school dropout rates. Their performance resembles that
      of first-generation youth in more established immigration gateways.

PMID- 22966927
TI  - Distinct trajectories in the transition to adulthood: are children of immigrants
      advantaged?
AB  - Studies on children of immigrants have generally ignored distinct developmental
      trajectories during adolescence and their role in the transition to adulthood.
      This study identifies distinct trajectories in cognitive, sociobehavioral, and
      psychological domains and estimates their consequences for young adults. Drawing
      data from a nationally representative sample of 10,795 adolescents aged 13-17 who
      were followed up to ages 25-32, the study uses growth mixture modeling to test
      advantages for children of immigrants. The analysis shows a 1.5-generation
      advantage in academic achievement and school engagement, as well as a weaker
      second-generation advantage in academic achievement, but no disadvantage in
      depression for children of immigrants. In addition, these results hold for
      children of Hispanic origin. Theoretical and policy implications are discussed.

PMID- 22966928
TI  - Acculturation or development? Autonomy expectations among ethnic German immigrant
      adolescents and their native German age-mates.
AB  - This longitudinal study compared immigrant and native adolescents' expectations
      concerning the timing of conventional socially acceptable and oppositional less
      socially acceptable forms of autonomy. Based on normative development and a
      collectivist background among immigrants, both developmental and acculturative
      change was expected. The sample consisted of 523 ethnic German immigrants from
      the former Soviet Union and 475 native German adolescents, both groups divided
      into an early (age 12.5years) and a late (age 16years) adolescent group. Results
      revealed more developmental than acculturative change, as immigrants and natives
      mostly showed a similar rate of change in autonomy expectations. Acculturative
      change was found only for oppositional autonomy among late adolescent immigrants,
      whose later expectations approached those of their native age-mates over time.

PMID- 22966929
TI  - Mexican-origin youth's cultural orientations and adjustment: changes from early
      to late adolescence.
AB  - Drawing from developmental and cultural adaptation perspectives and using a
      longitudinal design, this study examined: (a) mean-level changes in Mexican
      origin adolescents' cultural orientations and adjustment from early to late
      adolescence and (b) bidirectional associations between cultural orientations and
      adjustment using a cross-lag panel model. Participants included 246 Mexican
      origin, predominantly immigrant families that participated in home interviews and
      a series of nightly phone calls when target adolescents were 12 and 18years of
      age. Girls exhibited more pronounced declines in traditional gender role
      attitudes than did boys, and all youth declined in familism values, time spent
      with family, and involvement in Mexican culture. Bidirectional relations between
      cultural orientations and adjustment emerged, and some associations were
      moderated by adolescent nativity and gender.

PMID- 22966930
TI  - Resilience and well-being among children of migrant parents in South-East Asia.
AB  - There has been little systematic empirical research on the well-being of children
      in transnational households in South-East Asia-a major sending region for
      contract migrants. This study uses survey data collected in 2008 from children
      aged 9, 10, and 11 and their caregivers in Indonesia, the Philippines, and
      Vietnam (N=1,498). Results indicate that while children of migrant parents,
      especially migrant mothers, are less likely to be happy compared to children in
      nonmigrant households, greater resilience in child well-being is associated to
      longer durations of maternal absence. There is no evidence for a direct parental
      migration effect on school enjoyment and performance. The analyses highlight the
      sensitivity of results to the dimension of child well-being measured and who
      makes the assessment.

PMID- 22966932
TI  - In vitro fertilization pregnancy rates in levothyroxine-treated women with
      hypothyroidism.

PMID- 22966931
TI  - Effect of Ascaris Lumbricoides specific IgE on tuberculin skin test responses in
      children in a high-burden setting: a cross-sectional community-based study.
AB  - BACKGROUND: M.tuberculosis (M.tb) is associated with enhanced T helper cell type
      1 (Th1) immune responses while helminth infection is associated with T helper
      cell type 2 (Th2) immune responses. Our aim was to investigate whether helminth
      infection could influence the ability to generate an appropriate Th1 immune
      response that is characterized by a positive tuberculin skin test (TST), in M.tb
      exposed children. METHODS: We completed a community-based, cross sectional
      household contact tracing study, using matched enrolment of HIV negative children
      with and without documented household M.tb exposure. We documented demographics,
      clinical characteristics, HIV status, M.tb exposure (using a standard contact
      score) and M.tb infection status (TST > = 10 mm). Ascaris lumbricoides-specific
      IgE was used as proxy for Ascaris infection/exposure. RESULTS: Of 271 children
      (median age 4 years (range: 4 months to 15 years)) enrolled, 65 participants
      (24%) were serum positive for Ascaris IgE. There were 168 (62%) children with a
      documented household tuberculosis contact and 107 (40%) were (TST) positive
      overall.A positive TST was associated with increasing age (Odds Ratio (OR) =1.17,
      p < 0.001), increasing M.tb contact score (OR = 1.17, p < 0.001), previous
      tuberculosis treatment (OR = 4.8, p = 0.06) and previous isoniazid preventive
      treatment (OR = 3.16, p = 0.01). A visible bacillus Calmette-Guerin (BCG) scar
      was associated with reduced odds of being TST positive (OR = 0.42, p =
      0.01).Ascaris IgE was not associated with TST status in univariate analysis (OR =
      0.9, p = 0.6), but multivariable logistic regression analysis suggested an
      inverse association between Ascaris IgE status and a positive TST (OR = 0.6, p =
      0.08), when adjusted for age, and M.tb contact score. The addition of an age
      interaction term to the model suggested that the age effect was stronger among
      Ascaris IgE positive children; the effect of being Ascaris IgE positive
      significantly reduced the odds of being TST positive amongst younger children
      while this effect weakened with increasing age. CONCLUSIONS: Our preliminary
      findings highlight a high prevalence of both Ascaris exposure/infection and M.tb
      infection in children in an urban setting. Helminth exposure/infection may reduce
      the immune response following M.tb exposure when controlling for epidemiological
      and clinical covariates. These findings might be relevant to the interpretation
      of immunological tests of M.tb infection in children.

PMID- 22966933
TI  - Our approach to anticoagulation in patients undergoing device implants or
      replacement.

PMID- 22966935
TI  - IR spectroscopy of alpha- and beta-protonated pyrrole via argon complex
      photodissociation.
AB  - Protonated pyrrole cations are produced in a pulsed discharge/supersonic
      expansion source, mass-selected in a time-of-flight spectrometer, and studied
      with infrared photodissociation spectroscopy. Vibrational spectra in both the
      fingerprint and C-H/N-H stretching regions are obtained using the method of
      tagging with argon. Sharp vibrational structure is compared to IR spectra
      predicted by theory for the possible alpha-, beta-, and N-protonated structures.
      The spectral differences among these isomers are much larger than the frequency
      shifts due to argon attachment at alternative sites. Though alpha-protonation
      predominates thermodynamically, the kinetically favored beta-protonated species
      is also observed for the first time (in 3-4 times lower abundance under the
      conditions employed here). Theoretical investigations attribute the greater
      stability of alpha-protonated pyrrole to topological charge stabilization, rather
      than merely to the greater number of resonance contributors. The far-IR pattern
      of protonated pyrrole does not match the interstellar UIR bands.

PMID- 22966934
TI  - NaxD is a deacetylase required for lipid A modification and Francisella
      pathogenesis.
AB  - Modification of specific Gram-negative bacterial cell envelope components, such
      as capsule, O-antigen and lipid A, are often essential for the successful
      establishment of infection. Francisella species express lipid A molecules with
      unique characteristics involved in circumventing host defences, which
      significantly contribute to their virulence. In this study, we show that NaxD, a
      member of the highly conserved YdjC superfamily, is a deacetylase required for an
      important modification of the outer membrane component lipid A in Francisella.
      Mass spectrometry analysis revealed that NaxD is essential for the modification
      of a lipid A phosphate with galactosamine in Francisella novicida, a model
      organism for the study of highly virulent Francisella tularensis. Significantly,
      enzymatic assays confirmed that this protein is necessary for deacetylation of
      its substrate. In addition, NaxD was involved in resistance to the antimicrobial
      peptide polymyxin B and critical for replication in macrophages and in vivo
      virulence. Importantly, this protein is also required for lipid A modification in
      F. tularensis as well as Bordetella bronchiseptica. Since NaxD homologues are
      conserved among many Gram-negative pathogens, this work has broad implications
      for our understanding of host subversion mechanisms of other virulent bacteria.

PMID- 22966936
TI  - The genes of all seven CYP3A isoenzymes identified in the equine genome are
      expressed in the airways of horses.
AB  - In the present study, we examined the gene expression of cytochrome P450 3A
      (CYP3A) isoenzymes in the tracheal and bronchial mucosa and in the lung of
      equines using TaqMan probes. The results show that all seven CYP3A isoforms
      identified in the equine genome, that is, CYP3A89, CYP3A93, CYP3A94, CYP3A95,
      CYP3A96, CYP3A97 and CYP3A129, are expressed in the airways of the investigated
      horses. Though in previous studies, CYP3A129 was found to be absent in equine
      intestinal mucosa and liver, this CYP3A isoform is expressed in the airways of
      horses. The gene expression of the CYP3A isoenzymes varied considerably between
      the individual horses studied. However, in most of the horses CYP3A89, CYP3A93,
      CYP3A96, CYP3A97 and CYP3A129 were expressed to a high extent, while CYP3A94 and
      CYP3A95 were expressed to a low extent in the different parts of the airways. The
      CYP3A isoenzymes present in the airways may play a role in the metabolic
      degradation of inhaled xenobiotics. In some instances, the metabolism may,
      however, result in bioactivation of the xenobiotics and subsequent tissue injury.

PMID- 22966937
TI  - Consumption patterns of sweet drinks in a population of Australian children and
      adolescents (2003-2008).
AB  - BACKGROUND: Intake of sweet drinks has previously been associated with the
      development of overweight and obesity among children and adolescents. The present
      study aimed to assess the consumption pattern of sweet drinks in a population of
      children and adolescents in Victoria, Australia. METHODS: Data on 1,604 children
      and adolescents (4-18 years) from the comparison groups of two quasi-experimental
      intervention studies from Victoria, Australia were analysed. Sweet drink
      consumption (soft drink and fruit juice/cordial) was assessed as one day's intake
      and typical intake over the last week or month at two time points between 2003
      and 2008 (mean time between measurement: 2.2 years). RESULTS: Assessed using
      dietary recalls, more than 70% of the children and adolescents consumed sweet
      drinks, with no difference between age groups (p = 0.28). The median intake among
      consumers was 500 ml and almost a third consumed more than 750 ml per day. More
      children and adolescents consumed fruit juice/cordial (69%) than soft drink (33%)
      (p < 0.0001) and in larger volumes (median intake fruit juice/cordial: 500 ml and
      soft drink: 375 ml). Secular changes in sweet drink consumption were observed
      with a lower proportion of children and adolescents consuming sweet drinks at
      time 2 compared to time 1 (significant for age group 8 to <10 years, p = 0.001).
      CONCLUSION: The proportion of Australian children and adolescents from the state
      of Victoria consuming sweet drinks has been stable or decreasing, although a high
      proportion of this sample consumed sweet drinks, especially fruit juice/cordial
      at both time points.

PMID- 22966938
TI  - cis-4-amino-L-proline residue as a scaffold for the synthesis of cyclic and
      linear endomorphin-2 analogues: part 2.
AB  - Recently, we reported synthesis and activity of a constrained cyclic analogue of
      endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) and related linear models containing
      the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present
      article, the adopted rationale is the possible modulation of the receptor
      affinity of the cAmp containing EM-2 analogues by assigning a different
      stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus,
      eight more analogues with different absolute configuration at the chiral center
      of the aromatic residues in positions 3 and 4 have been synthesized and their
      opioid activity examined. The stereochemical change at the alpha-carbon atoms
      leads to a meaningful enhancement of the affinity and activity toward MU opioid
      receptors with respect to the prototype compound 9: e.g., 9a, K(i)(MU) = 63 nM,
      GPI (IC(50)) = 480 nM; 9b, K(i)(MU) = 38 nM, GPI (IC(50)) = 330 nM.

PMID- 22966939
TI  - Truncated tetrahedron seed crystals initiating stereoaligned growth of FeSi
      nanowires.
AB  - We have synthesized epitaxially grown freestanding FeSi nanowires (NWs) on an m
      Al(2)O(3) substrate by using a catalyst-free chemical vapor transport method.
      FeSi NW growth is initiated from FeSi nanocrystals, formed on a substrate in a
      characteristic shape with a specific orientation. Cross-section TEM analysis of
      seed crystals reveals the crystallographic structure and hidden geometry of the
      seeds. Close correlation of geometrical shapes and orientations of the observed
      nanocrystals with those of as-grown NWs indicates that directional growth of NWs
      is initiated from the epitaxially formed seed crystals. The diameter of NWs can
      be controlled by adjusting the composition of Si in a Si/C mixture. The epitaxial
      growth method for FeSi NWs via seed crystals could be employed to heteroepitaxial
      growth of other compound NWs.

PMID- 22966940
TI  - How safe is it to manage diverticular colovesical fistulation non-operatively?
AB  - AIM: Colovesical fistula (CVF) is an uncommon condition. Diagnosis and management
      varies according to presentation and aetiology. The identification of patients
      suitable for conservative management and their outcome following this approach
      has not been well documented. METHODS: The clinical outcomes of all patients
      diagnosed with a CVF over a 7-year period from an uro-radiological database were
      reviewed. Cases secondary to diverticular disease were analysed with respect to
      the approach by which they were managed: those treated surgically and those
      managed conservatively. RESULTS: Sixty-two patients (32 men) were diagnosed with
      CVF of whom 53 (85%) had diverticular disease. Twenty-seven (mean age 69 years,
      range 42-90) underwent surgery (with a stoma in 59%) with a 30-day mortality of
      15%. Those managed conservatively (n = 26) were older (mean age 76 years, range
      39-87) and frailer (62% American Society of Anesthesiologists Grades III and IV).
      At 1 and 3 years following diagnosis there was no difference in mortality between
      these two groups and only one death was as a consequence of urosepsis.
      CONCLUSION: Many patients with CVF secondary to diverticular disease can be
      safely managed non-operatively.

PMID- 22966941
TI  - Network enrichment analysis: extension of gene-set enrichment analysis to gene
      networks.
AB  - BACKGROUND: Gene-set enrichment analyses (GEA or GSEA) are commonly used for
      biological characterization of an experimental gene-set. This is done by finding
      known functional categories, such as pathways or Gene Ontology terms, that are
      over-represented in the experimental set; the assessment is based on an overlap
      statistic. Rich biological information in terms of gene interaction network is
      now widely available, but this topological information is not used by GEA, so
      there is a need for methods that exploit this type of information in high
      throughput data analysis. RESULTS: We developed a method of network enrichment
      analysis (NEA) that extends the overlap statistic in GEA to network links between
      genes in the experimental set and those in the functional categories. For the
      crucial step in statistical inference, we developed a fast network randomization
      algorithm in order to obtain the distribution of any network statistic under the
      null hypothesis of no association between an experimental gene-set and a
      functional category. We illustrate the NEA method using gene and protein
      expression data from a lung cancer study. CONCLUSIONS: The results indicate that
      the NEA method is more powerful than the traditional GEA, primarily because the
      relationships between gene sets were more strongly captured by network
      connectivity rather than by simple overlaps.

PMID- 22966943
TI  - The late recurrence of ganglioneuroma 21 years after initial presentation with
      neuroblastoma.
AB  - A 3-year-old boy presented with tumors in the adrenal gland and the right orbit,
      and was diagnosed with neuroblastoma. After chemotherapy, the tumors were
      resected and the pathological diagnoses of ganglioneuroblastoma in the adrenal
      gland and ganglioneuroma in the orbit were made. The tumor relapsed at the
      intracranial dura mater 21 years after the initial diagnosis, and was diagnosed
      as ganglioneuroma from a biopsied sample. This case is very unique in that
      ganglioneuroma matured from ganglioneuroblastoma or neuroblastoma had the late
      recurrence with 21 years of tumor dormancy.

PMID- 22966942
TI  - Left ventricular markers of global dyssynchrony predict limited exercise capacity
      in heart failure, but not in patients with preserved ejection fraction.
AB  - BACKGROUND: The aim of this study was to prospectively examine echocardiographic
      parameters that correlate and predict functional capacity assessed by 6 min walk
      test (6-MWT) in patients with heart failure (HF), irrespective of ejection
      fraction (EF). METHODS: In 147 HF patients (mean age 61 +/- 11 years, 50.3%
      male), a 6-MWT and an echo-Doppler study were performed in the same day. Global
      LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in
      s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei
      index (t-IVT/ejection time). Patients were divided into two groups based on the 6
      MWT distance (Group I: <= 300 m and Group II: >300 m), and also in two groups
      according to EF (Group A: LVEF >= 45% and Group B: LVEF < 45%). RESULTS: In the
      cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p <
      0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other
      clinical or echocardiographic parameters. Group I had lower hemoglobin level (p =
      0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker
      interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late
      diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time
      (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients
      cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF
      [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04]
      independently predicted poor 6-MWT performance (<300 m) in multivariate analysis.
      None of the echocardiographic measurements predicted exercise tolerance in HFpEF.
      CONCLUSION: In patients with HF, the limited exercise capacity, assessed by 6
      MWT, is related mostly to severity of global LV dyssynchrony, more than EF or
      raised filling pressures. The lack of exercise predictors in HFpEF reflects its
      multifactorial pathophysiology.

PMID- 22966944
TI  - Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and
      the risk of childhood acute lymphoblastic leukemia.
AB  - Our aim was to address the hypothesis that maternal dietary intake of folate
      during pregnancy is inversely associated with risk of acute lymphoblastic
      leukemia (ALL) in the offspring. Dietary intake of folate, vitamins B6 and B12 in
      the last 6 mo of pregnancy from 333 cases and 695 frequency-matched controls were
      assessed using a food frequency questionnaire. Data were analyzed using
      unconditional logistic regression, adjusting for study matching variables, total
      energy, and potentially confounding variables. Higher levels of dietary folate
      and B12 appeared to be associated with a decreased risk of ALL. Higher levels of
      vitamin B6 were associated with an increased risk. The strongest associations of
      ALL with these variables were seen when mothers consumed alcohol in pregnancy.
      Our findings are consistent with a modest protective effect of higher dietary
      intake of folate and vitamin B12 against ALL in the offspring, more particularly
      among women who drank alcohol during pregnancy. These findings are consistent
      with previous reports of the protective effects of a maternal diet high in fruit,
      vegetables, and nondairy protein sources. The vitamin B6 findings are not
      consistent with evidence that it is a protective factor against other cancers,
      and may be a chance finding.

PMID- 22966945
TI  - Preparation of synthetically challenging nucleotides using cyanoethyl P
      imidazolides and microwaves.
AB  - We describe a general method for the elongation of nucleoside oligophosphate
      chains by means of cyanoethyl (CE) phosphorimidazolides. Though the method
      requires a phosphorylation and subsequent deprotection reaction, both steps could
      be achieved in one pot without isolation/purification of the initial
      phosphorylation product. We have also found that pyrophosphate bond formation by
      this method is significantly accelerated by microwave irradiation.

PMID- 22966946
TI  - Review article: the reversibility of cirrhosis.
AB  - BACKGROUND: Cirrhosis is the end result of many types of chronic liver diseases.
      Recent developments in the understanding of the process of hepatic fibrogenesis
      have revealed that the process is a dynamic one and a capacity for recovery from
      any degree of fibrosis including those associated with cirrhosis is plausible.
      AIM: To review current evidence of histopathological reversibility following drug
      therapy of more common aetiologies of cirrhosis. METHODS: A PubMed search was
      performed and the evidence for histopathological regression of advanced
      fibrosis/cirrhosis following drug therapy was reviewed as of the end of February
      2012. RESULTS: There is abundant clinical evidence in support of the idea of the
      reversibility of cirrhosis in patients with different aetiologies of advanced
      hepatic disease including viral, autoimmune and metabolic/infiltrative liver
      disease. CONCLUSIONS: The concept of cirrhosis has changed from being a form of
      static and irreversible entity to a dynamic and reversible diseases stage. Novel
      therapeutic strategies are under investigation to target specific steps in the
      process of fibrogenesis with the aim of reversing advanced fibrosis/cirrhosis.

PMID- 22966947
TI  - Quality-adjusted life years in cancer: pros, cons, and alternatives.
AB  - High and rising cancer treatment costs have forced a discussion about the use of
      cost-effectiveness analyses and other approaches to assess the value of cancer
      care. Oncologists have traditionally resisted using economic considerations in
      day-to-day medical considerations, though unavoidably their decisions have
      important resource implications, and increasingly economic realities are
      impacting their actions. In this paper, we summarise the use of the quality
      adjusted life years to assess the value of cancer care and suggest potential ways
      to improve upon value measurement in cancer coverage and reimbursement decisions.

PMID- 22966949
TI  - Vapor-deposited parylene photoresist: a multipotent approach toward chemically
      and topographically defined biointerfaces.
AB  - Poly(4-benzoyl-p-xylylene-co-p-xylylene), a biologically compatible photoreactive
      polymer belonging to the parylene family, can be deposited using a chemical vapor
      deposition (CVD) polymerization process on a wide range of substrates. This study
      discovered that the solvent stability of poly(4-benzoyl-p-xylylene-co-p-xylylene)
      in acetone is significantly increased when exposed to approximately 365 nm of UV
      irradiation, because of the cross-linking of benzophenone side chains with
      adjacent molecules. This discovery makes the photodefinable polymer a powerful
      tool for use as a negative photoresist for surface microstructuring and
      biointerface engineering purposes. The polymer is extensively characterized using
      infrared reflection adsorption spectroscopy (IRRAS), scanning electron microscopy
      (SEM), and imaging ellipsometry. Furthermore, the vapor-based polymer coating
      process provides access to substrates with unconventional and complex three
      dimensional (3D) geometries, as compared to conventional spin-coated resists that
      are limited to flat 2D assemblies. Moreover, this photoresist technology is
      seamlessly integrated with other functionalized parylenes including aldehyde-,
      acetylene-, and amine-functionalized parylenes to create unique surface
      microstructures that are chemically and topographically defined. The
      photopatterning and immobilization protocols described in this paper represent an
      approach that avoids contact between harmful substances (such as solvents and
      irradiations) and sensitive biomolecules. Finally, multiple biomolecules on
      planar substrates, as well as on unconventional 3D substrates (e.g., stents), are
      presented.

PMID- 22966948
TI  - Molecular mechanism of action of immune-modulatory drugs thalidomide,
      lenalidomide and pomalidomide in multiple myeloma.
AB  - Although several mechanisms have been proposed to explain the activity of
      thalidomide, lenalidomide and pomalidomide in multiple myeloma (MM), including
      demonstrable anti-angiogenic, anti-proliferative and immunomodulatory effects,
      the precise cellular targets and molecular mechanisms have only recently become
      clear. A landmark study recently identified cereblon (CRBN) as a primary target
      of thalidomide teratogenicity. Subsequently it was demonstrated that CRBN is also
      required for the anti-myeloma activity of thalidomide and related drugs, the so
      called immune-modulatory drugs (IMiDs). Low CRBN expression was found to
      correlate with drug resistance in MM cell lines and primary MM cells. One of the
      downstream targets of CRBN identified is interferon regulatory factor 4 (IRF4),
      which is critical for myeloma cell survival and is down-regulated by IMiD
      treatment. CRBN is also implicated in several effects of IMiDs, such as down
      regulation of tumor necrosis factor-alpha (TNF-alpha) and T cell immunomodulatory
      activity, demonstrating that the pleotropic actions of the IMiDs are initiated by
      binding to CRBN. Future dissection of CRBN downstream signaling will help to
      delineate the underlying mechanisms for IMiD action and eventually lead to
      development of new drugs with more specific anti-myeloma activities. It may also
      provide a biomarker to predict IMiD response and resistance.

PMID- 22966951
TI  - Sudden unexpected death related to enterovirus myocarditis: histopathology,
      immunohistochemistry and molecular pathology diagnosis at post-mortem.
AB  - BACKGROUND: Viral myocarditis is a major cause of sudden unexpected death in
      children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the
      most commonly implicated virus in myocarditis. At present, no standard diagnosis
      is generally accepted due to the insensitivity of traditional diagnostic tests.
      This has prompted health professionals to seek new diagnostic approaches, which
      resulted in the emergence of new molecular pathological tests and a more detailed
      immunohistochemical and histopathological analysis. When supplemented with
      immunohistochemistry and molecular pathology, conventional histopathology may
      provide important clues regarding myocarditis underlying etiology. METHODS: This
      study is based on post-mortem samples from sudden unexpected death victims and
      controls who were investigated prospectively. Immunohistochemical investigations
      for the detection of the enteroviral capsid protein VP1 and the characterization
      and quantification of myocardial inflammatory reactions as well as molecular
      pathological methods for enteroviral genome detection were performed. RESULTS:
      Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37
      cases of unnatural traffic accident victims were studied. Enterovirus was
      detected in 6 sudden unexpected death cases (12.5 %). The control samples were
      completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1
      in the myocardium was detected in enterovirus-positive cases revealed by means of
      reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples,
      immunohistochemical investigations showed a significant presence of T and B
      lymphocytes in sudden unexpected death victims. CONCLUSIONS: Our findings
      demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden
      unexpected death compared to control subjects, suggesting that coxsackie B
      enterovirus may contribute to myocarditis pathogenesis significantly.

PMID- 22966952
TI  - Feasibility of defibrillation and automatic arrhythmia detection using an
      exclusively subcutaneous defibrillator system in canines.
AB  - INTRODUCTION: This study reports the experimental process leading to development
      of an automatic totally subcutaneous implantable cardioverter defibrillator
      (SICD) system engineered for human use. METHODS AND RESULTS: Two studies were
      conducted to test defibrillation and detection feasibility of an SICD system
      located in the left chest. In the first study, 2 pockets were created in 15
      canines for placement of an anterior electrode adjacent to the left edge of the
      sternum and a lateral electrode at the site along the axillary line between the
      4th and 6th intercostal space. Stainless steel flat electrodes with active
      surface areas of 5, 10, 20, and 25 cm(2) or rod electrodes were subsequently
      positioned and the defibrillation threshold (DFT) was measured for multiple
      combinations. In the second study, the ability to induce, detect, and provide
      shock delivery in response to ventricular fibrillation (VF) using an SICD system
      engineered for clinical use was tested in 5 canines. One hundred and three DFT
      tests with 11 different dual electrode combinations were performed. All
      combinations terminated VF with a DFT of 35 +/- 16 J (range: 9-79 J). Nineteen VF
      episodes were induced and recognized by the chronic SICD, leading to automatic
      capacitor charge and shock delivery in all cases. CONCLUSIONS: Subcutaneous
      defibrillation using different electrode combinations with shock energies less
      than 80 J terminated all induced VFs. An automatic SICD proved effective in
      detecting and activating shock delivery in all cases. 

PMID- 22966953
TI  - Hearing difficulties, ear-related diagnoses and sickness absence or disability
      pension--a systematic literature review.
AB  - BACKGROUND: Hearing difficulties is a large public health problem, prognosticated
      to be the ninth leading burden of disease in 2030, and may also involve large
      consequences for work capacity. However, research regarding sickness absence and
      disability pension in relation to hearing difficulties is scarce. The aim was to
      gain knowledge about hearing difficulties or other ear-related diagnoses and
      sickness absence and disability pension through conducting a systematic
      literature review of published studies. METHODS: Studies presenting empirical
      data on hearing difficulties or ear-related diagnoses and sick leave or
      disability pension, published in scientific peer-reviewed journals, were
      included. Studies were sought for in three ways: in literature databases (Pub
      Med, Embase, PsycInfo, SSCI, and Cochrane) through March 2011, through
      scrutinising lists of references, and through contacts. Identified publications
      were assessed for relevance and data was extracted from the studies deemed
      relevant. RESULTS: A total of 18 studies were assessed as relevant and included
      in this review, regardless of scientific quality. Fourteen studies presented
      empirical data on hearing difficulties/ear diagnoses and sick leave and six on
      these conditions and disability pension. Only two studies presented rate ratios
      or odds ratios regarding associations between hearing difficulties and sick
      leave, and only two on hearing difficulties and risk of disability pension. Both
      measures of hearing difficulties and of sick leave varied considerable between
      the studies. CONCLUSIONS: Remarkably few studies on hearing difficulties in
      relation to sickness absence or disability pension were identified. The results
      presented in them cannot provide evidence for direction or magnitude of potential
      associations.

PMID- 22966954
TI  - Photochemical isomerizations of thiosemicarbazide, a matrix isolation study.
AB  - Two thione conformers of monomeric thiosemicarbazide were trapped from the gas
      phase into a low-temperature Ar matrix. A phototransformation converting the less
      stable form of the compound into the most stable conformer was induced by
      irradiation with near-IR (lambda = 1462 nm) or UV (lambda > 320 nm) light. This
      photoeffect allowed separation of the IR spectra of the observed thione forms.
      The structures of both observed isomers were identified by comparison of the
      separated experimental IR spectra with the spectra theoretically predicted for
      two most stable forms of the compound. The population ratio of the two conformers
      in an Ar matrix, prior to any irradiation, was estimated to be equal ~2:1.
      Irradiation of matrix-isolated thiosemicarbazide with shorter-wavelength UV
      (lambda > 270 nm) light induced a phototautomeric reaction generating thiol forms
      of the compound.

PMID- 22966955
TI  - Catalytic deoxyribozyme-modified nanoparticles for RNAi-independent gene
      regulation.
AB  - DNAzymes are catalytic oligonucleotides with important applications in gene
      regulation, DNA computing, responsive soft materials, and ultrasensitive metal
      ion sensing. The most significant challenge for using DNAzymes in vivo pertains
      to nontoxic delivery and maintaining function inside cells. We synthesized
      multivalent deoxyribozyme "10-23" gold nanoparticle (DzNP) conjugates, varying
      DNA density, linker length, enzyme orientation, and linker composition in order
      to study the role of the steric environment and gold surface chemistry on
      catalysis. DNAzyme catalytic efficiency was modulated by steric packing and
      proximity of the active loop to the gold surface. Importantly, the 10-23 DNAzyme
      was asymmetrically sensitive to the gold surface and when anchored through the 5'
      terminus was inhibited 32-fold. This property was used to generate DNAzymes whose
      catalytic activity is triggered by thiol displacement reactions or by
      photoexcitation at lambda = 532 nm. Importantly, cell studies revealed that DzNPs
      are less susceptible to nuclease degradation, readily enter mammalian cells, and
      catalytically down-regulate GDF15 gene expression levels in breast cancer cells,
      thus addressing some of the key limitations in the adoption of DNAzymes for in
      vivo work.

PMID- 22966956
TI  - Incontinence in full-thickness rectal prolapse: low level of improvement after
      laparoscopic rectopexy.
AB  - AIM: The study aimed to quantify incontinence before and after laparoscopic
      rectopexy in patients suffering from rectal prolapse. METHOD: Eighty-five
      patients underwent laparoscopic rectopexy to treat rectal prolapse between 2003
      and 2009. Symptomatic and functional data were collected prospectively before and
      after surgery by self-administered questionnaires including the Cleveland Clinic
      Fecal Incontinence Score (CCIS) and constipation, gastrointestinal quality of
      life and urinary incontinence questionnaires. Incontinence was considered to be
      present when the CCIS remained at >= 5 after surgery. RESULTS: After a mean
      follow-up period of 36 months after surgery, 83% of the patients reported good to
      excellent results. Continence was improved in 58 (68%), with a significant
      decrease in the continence score (-3.4 +/- 5.8, P = 0.001). However, 50 (58.9%)
      patients remained incontinent: 47 (55%) reported urge incontinence and 27 (32%)
      had passive leakage. Incontinence for liquid stool, incontinence for solid stool
      and the need for protection was seen in 43 (51%), 35 (41%) and 43 (51%) patients.
      Manometry, defaecography and ultrasonography were not associated with any
      improvement. In contrast, the patients' average age (60.2 +/- 15.8 vs 46.9 +/-
      15.5 years; P = 0.003), symptom duration before surgery (58.1 +/- 70.1 vs 29.5 +/
      33.3 months; P = 0.011), preoperative urinary incontinence score (10.7 +/- 10.8
      vs 4.2 +/- 5.7; P = 0.0131) and faecal incontinence score (12.9 +/- 4.9 vs 7.1 +/
      6; P < 0.0001) were significantly higher in patients suffering from
      postoperative incontinence. CONCLUSION: Despite some continence improvement in
      two-thirds of patients who underwent surgery for rectal prolapse, the level of
      improvement remained low in more than half of the patients.

PMID- 22966957
TI  - [(99m)Tc]Demomedin C, a radioligand based on human gastrin releasing peptide(18
      27): synthesis and preclinical evaluation in gastrin releasing peptide receptor
      expressing models.
AB  - The synthesis and preclinical evaluation of [(99m)Tc]Demomedin C in GRPR
      expressing models are reported. Demomedin C resulted by coupling a Boc-protected
      N(4)-chelator to neuromedin C (human GRP(18-27)), which, after (99m)Tc-labeling,
      afforded [(99m)Tc]Demomedin C. Demomedin C showed high affinity and selectivity
      for the GRPR during receptor autoradiography on human cancer samples (IC(50) in
      nM: GRPR, 1.4 +/- 0.2; NMBR, 106 +/- 18; and BB(3)R, >1000). It triggered GRPR
      internalization in HEK-GRPR cells and Ca(2+) release in PC-3 cells (EC(50) = 1.3
      nM). [(99m)Tc]Demomedin C rapidly and specifically internalized at 37  degrees C
      in PC-3 cells and was stable in mouse plasma. [(99m)Tc]Demomedin C efficiently
      and specifically localized in human PC-3 implants in mice (9.84 +/- 0.81%ID/g at
      1 h pi; 6.36 +/- 0.85%ID/g at 4 h pi, and 0.41 +/- 0.07%ID/g at 4 h pi block).
      Thus, human GRP-based radioligands, such as [(99m)Tc]Demomedin C, can
      successfully target GRPR-expressing human tumors in vivo while displaying
      attractive biological features--e.g. higher GRPR-selectivity--vs their frog
      homologues.

PMID- 22966958
TI  - The top-scoring 'N' algorithm: a generalized relative expression classification
      method from small numbers of biomolecules.
AB  - BACKGROUND: Relative expression algorithms such as the top-scoring pair (TSP) and
      the top-scoring triplet (TST) have several strengths that distinguish them from
      other classification methods, including resistance to overfitting, invariance to
      most data normalization methods, and biological interpretability. The top-scoring
      'N' (TSN) algorithm is a generalized form of other relative expression algorithms
      which uses generic permutations and a dynamic classifier size to control both the
      permutation and combination space available for classification. RESULTS: TSN was
      tested on nine cancer datasets, showing statistically significant differences in
      classification accuracy between different classifier sizes (choices of N). TSN
      also performed competitively against a wide variety of different classification
      methods, including artificial neural networks, classification trees, discriminant
      analysis, k-Nearest neighbor, naive Bayes, and support vector machines, when
      tested on the Microarray Quality Control II datasets. Furthermore, TSN exhibits
      low levels of overfitting on training data compared to other methods, giving
      confidence that results obtained during cross validation will be more generally
      applicable to external validation sets. CONCLUSIONS: TSN preserves the strengths
      of other relative expression algorithms while allowing a much larger permutation
      and combination space to be explored, potentially improving classification
      accuracies when fewer numbers of measured features are available.

PMID- 22966960
TI  - Mutated Ras-transfected, EBV-transformed lymphoblastoid cell lines as a model
      tumor vaccine for boosting T-cell responses against pancreatic cancer: a pilot
      trial.
AB  - Genetically modified lymphoblastoid cell lines (LCL) have been shown to be an
      attractive alternative source of antigen-presenting cells for cancer vaccination
      in vitro. We tested their application in patients with pancreatic cancer in a
      phase I clinical trial. As a model tumor antigen, we selected the point-mutated
      (codon 12) Ki-Ras p21 oncogene (muRas) frequently (~85%) present in pancreatic
      adenocarcinoma. Autologous LCLs were established in vitro by spontaneous
      outgrowth from peripheral blood lymphocytes of seven pancreatic carcinoma
      patients and were genetically modified with an episomal Epstein-Barr virus (EBV)
      based expression vector to express muRas (muRas-LCL). Weekly vaccinations with
      subcutaneous injection of 5*10(6) muRas-LCL were done. In six of seven patients,
      therapeutic vaccination elicited a T-cell response with an increase in the
      frequency of muRas-specific precursor cytotoxic T lymphocytes in the peripheral
      blood and positive delayed-type hypersensitivity reactions at the injection site.
      Besides local reactions and flu-like symptoms, there were no signs of toxicity
      and no acute EBV infection, onset of EBV-associated lymphoma, or other severe
      complications. A clinical response (stable disease) was observed for a short time
      period (2-4 months) in four of seven patients (57%), mostly in earlier tumor
      stages. Our results indicate that LCL presenting genetically modified antigen
      represent a valuable and easily available tool for in vivo autologous tumor
      vaccination. LCL can be transfected with any known tumor antigen and therefore
      should be further clinically investigated.

PMID- 22966961
TI  - The contribution of platelets to the pathogenesis of Raynaud's phenomenon and
      systemic sclerosis.
AB  - Raynaud's phenomenon (RP) describes the excessive vascular response of the
      digital vessels in response to cold exposure and emotional stress. It is
      typically the earliest manifestation of systemic sclerosis (SSc), a multisystem
      disease of unknown aetiology characterised by vasculopathy, inflammation and
      fibrosis. The biological actions of platelets are known to extend beyond primary
      haemostasis with a growing appreciation of their contribution to vascular
      function, inflammation and wound repair. This has led to a considerable body of
      work evaluating associations between platelet function analysis and RP/SSc. This
      review provides a conceptual framework upon which the potential contribution of
      platelets to vascular dysfunction, autoimmunity and tissue remodelling in RP and
      SSc is considered. We describe the existing evidence to support excessive
      platelet activation in RP and SSc, ranging from the early studies of platelet
      aggregability and circulating platelet-derived mediators, to the important
      findings of the recent work that has begun to explore the potential direct
      pathogenic role of platelets in established murine models of SSc. We shall
      describe and critically appraise the findings of previous therapeutic studies
      evaluating the use of anti-platelet agents in RP and SSc, along with their
      implications for future therapeutic intervention in these conditions. 

PMID- 22966959
TI  - Understanding determinants of nutrition, physical activity and quality of life
      among older adults: the Wellbeing, Eating and Exercise for a Long Life (WELL)
      study.
AB  - BACKGROUND: Nutrition and physical activity are major determinants of health and
      quality of life; however, there exists little research focusing on determinants
      of these behaviours in older adults. This is important, since just as these
      behaviours vary according to subpopulation, it is likely that the determinants
      also vary. An understanding of the modifiable determinants of nutrition and
      physical activity behaviours among older adults to take into account the specific
      life-stage context is required in order to develop effective interventions to
      promote health and well-being and prevent chronic disease and improve quality of
      life. METHODS: The aim of this work is to identify how intrapersonal, social and
      environmental factors influence nutrition and physical activity behaviours among
      older adults living in urban and rural areas. This study is a cohort study of
      adults aged 55-65 years across urban and rural Victoria, Australia. Participants
      completed questionnaires at baseline in 2010 and will complete follow-up
      questionnaires in 2012 and 2014. Self-report questionnaires will be used to
      assess outcomes such as food intake, physical activity and sedentary behaviours,
      anthropometry and quality of life. Explanatory variables include socioeconomic
      position, and measures of the three levels of influence on older adults'
      nutrition and physical activity behaviours (intrapersonal, social and perceived
      environmental influences). DISCUSSION: Obesity and its determinant behaviours,
      physical inactivity and poor diet are major public health concerns and are
      significant determinants of the quality of life among the ageing population.
      There is a critical need for a better understanding of the determinants of
      nutrition and physical activity in this important target group. This research
      will provide evidence for the development of effective policies and programs to
      promote and support increased physical activity and healthy eating behaviours
      among older adults.

PMID- 22966963
TI  - The effects of Oxazyme on oxalate degradation: results and implications of in
      vitro experiments.
AB  - Abstract Background and Purpose: Urinary oxalate excretion influences the
      development of calcium oxalate kidney stones. Urinary oxalate is derived from
      dietary sources and endogenous synthesis. Oxalate decarboxylase metabolizes
      oxalate and, if consumed, could theoretically accomplish this in the
      gastrointestinal tract. This study aimed to determine whether a commercially
      produced form of oxalate decarboxylase (Oxazyme((r))) could degrade oxalate in
      simulated gastric and intestinal environments. MATERIALS AND METHODS: One buffer
      (pH 3.6) simulated the gastric environment, while another (pH 6.5), approximated
      the proximal intestine. Potassium oxalate (soluble form of oxalate) and whole and
      homogenized spinach (a high oxalate containing food) were incubated in the
      different buffered solutions, with or without Oxazyme. Oxalate content, after
      incubation, was measured using established ion chromatographic techniques.
      RESULTS: Oxazyme resulted in complete degradation of oxalate derived from
      potassium oxalate in the intestinal buffer; meanwhile, oxalate derived from
      potassium oxalate in the gastric buffer was profoundly digested by Oxazyme.
      Adding Oxazyme also substantially reduced the oxalate content of both whole and
      homogenized spinach preparations, in either buffer. CONCLUSIONS: These in vitro
      findings demonstrate that Oxazyme can metabolize oxalate in both simulated
      gastric and small intestinal environments.

PMID- 22966964
TI  - Iron-catalyzed cross-coupling of N-heterocyclic chlorides and bromides with
      arylmagnesium reagents.
AB  - A simple, practical iron salt catalyzed procedure allows fast cross-couplings of
      N-heterocyclic chlorides and bromides with various electron-rich and -poor
      arylmagnesium reagents. A solvent mixture of THF and tBuOMe is found to be
      essential for achieving high yields mainly by avoiding homocoupling side
      reactions.

PMID- 22966965
TI  - Epigenetic inheritance: a contributor to species differentiation?
AB  - Multiple epigenetic states can be associated with the same genome, and
      transmitted through the germline for generations, to create the phenomenon of
      epigenetic inheritance. This form of inheritance is mediated by complex and
      highly diverse components of the chromosome that associate with DNA, control its
      transcription, and are inherited alongside it. But, how extensive, and how
      stable, is the information carried in the germline by the epigenome? Several
      known examples of epigenetic inheritance demonstrate that it has the ability to
      create selectable traits, and thus to mediate Darwinian evolution. Here we
      discuss the possibility that epigenetic inheritance is responsible for some
      stable characteristics of species, focusing on a recent comparison of the human
      and chimpanzee methylomes which reveals that somatic methylation states are
      related to methylation states in the germline. Interpretation of this finding
      highlights the potential significance of germline epigenetic states, as well as
      the challenge of investigating a form of inheritance with complex and unfamiliar
      rules.

PMID- 22966966
TI  - Cancer patients and positive sensory impressions in the hospital environment--a
      qualitative interview study.
AB  - This study explores how cancer patients experience the meaning of positive
      sensory impressions in the hospital environment such as architecture, decoration
      and the interior. Data were obtained at a general hospital in Denmark by
      interviewing six cancer patients at two different wards. The analysis process was
      guided by the hermeneutical-phenomenological theory of interpretation as
      presented by the French philosopher Paul Ricoeur. Two main themes were
      identified: to preserve identity and positive thoughts and feelings. The
      participants experienced that positive sensory impressions in the hospital
      environment had a significant impact on their mood, generating positive thoughts
      and feelings. A view to nature also helped them to forget their negative thoughts
      for a while. The possibility of having a view helped some cancer patients to
      connect with good memories and personal life stories that enabled them to recall
      some of their feelings of identity. This paper adds knowledge about how cancer
      patients experience sensory impressions in the hospital environment. An
      environment that provides homeliness and offers a view to nature seems to help
      some patients to preserve their identity. Furthermore, positive sensory
      impressions and the opportunity for recreation through environmental facilities
      strengthen the patient's positive thoughts and feelings.

PMID- 22966967
TI  - Proton pump inhibitors are associated with a high rate of serious infections in
      veterans with decompensated cirrhosis.
AB  - BACKGROUND: There is increasing evidence that proton pump inhibitors (PPIs)
      increase the rate of infections in patients with decompensated cirrhosis. AIMS:
      To estimate the extent to which proton pump inhibitors (PPIs) increase the rate
      of infections among patients with decompensated cirrhosis. METHODS: We conducted
      a retrospective propensity-matched new user design using US Veterans Health
      Administration data. Only decompensated cirrhotic patients from 2001 to 2009 were
      included. New PPI users after decompensation (n = 1268) were 1:1 matched to those
      who did not initiate gastric acid suppression. Serious infections, defined as
      infections associated with a hospitalisation, were the outcomes. These were
      separated into acid suppression-related (SBP, bacteremia, Clostridium difficile
      and pneumonia) and non-acid suppression-related. Time-varying Cox models were
      used to estimate adjusted hazard ratios (HR) and 95% CIs of serious infections.
      Parallel analyses were conducted with H2 receptor antagonists (H2RA). RESULTS:
      More than half of persons with decompensated cirrhosis were new users of gastric
      acid suppressants, with most using PPIs (45.6%) compared with H2RAs (5.9%). In
      the PPI propensity-matched analysis, 25.3% developed serious infections and 25.9%
      developed serious infections in the H2RA analysis. PPI users developed serious
      infections faster than nongastric acid suppression users (adjusted HR: 1.66; 95%
      CI: 1.31-2.12). For acid suppression-related serious infections, PPI users
      developed the outcome at a rate 1.75 times faster than non-users (95% CI: 1.32
      2.34). The H2RA findings were not statistically significant (HR serious
      infections: 1.59; 95% CI: 0.80-3.18; HR acid suppression-related infections:
      0.92; 95% CI: 0.31-2.73). CONCLUSION: Among patients with decompensated
      cirrhosis, proton pump inhibitors but not H2 receptor antagonists increase the
      rate of serious infections.

PMID- 22966969
TI  - Abstracts of the 10th European Congress on Epileptology. London, United Kingdom.
      September 30-October 4, 2012.

PMID- 22966968
TI  - Competitive sorption kinetics of inhibited endo- and exoglucanases on a model
      cellulose substrate.
AB  - For the first time, the competitive adsorption of inhibited cellobiohydrolase I
      (Cel7A, an exoglucanase) and endoglucanase I (Cel7B) from T. longibrachiatum is
      studied on cellulose. Using quartz crystal microgravimetry (QCM), sorption
      histories are measured for individual types of cellulases and their mixtures
      adsorbing to and desorbing from a model cellulose surface. We find that Cel7A has
      a higher adsorptive affinity for cellulose than does Cel7B. The adsorption of
      both cellulases becomes irreversible on time scales of 30-60 min, which are much
      shorter than those typically used for industrial cellulose hydrolysis. A
      multicomponent Langmuir kinetic model including first-order irreversible binding
      is proposed. Although adsorption and desorption rate constants differ between the
      two enzymes, the rate at which each surface enzyme irreversibly binds is
      identical. Because of the higher affinity of Cel7A for the cellulose surface,
      when Cel7A and Cel7B compete for surface sites, a significantly higher bulk
      concentration of Cel7B is required to achieve comparable surface enzyme
      concentrations. Because cellulose deconstruction benefits significantly from the
      cooperative activity of endoglucanases and cellobiohydrolases on the cellulose
      surface, accounting for competitive adsorption is crucial to developing effective
      cellulase mixtures.

PMID- 22966970
TI  - Suboptimal medical care of patients with ST-elevation myocardial infarction and
      renal insufficiency: results from the Korea Acute Myocardial Infarction Registry.
AB  - BACKGROUND: The clinical outcomes of ST-segment elevation myocardial infarction
      (STEMI) are poor in patients with renal insufficiency. This study investigated
      changes in the likelihood that patients received optimal medical care throughout
      the entire process of myocardial infarction management, on the basis of their
      glomerular filtration rate (GFR). METHODS: This study analyzed 7,679 patients
      (age, 63 +/- 13 years; men 73.6%) who had STEMI and were enrolled in the Korea
      Acute Myocardial Infarction Registry (KAMIR) from November 2005 to August 2008.
      The study subjects were divided into 5 groups corresponding to strata used to
      define chronic kidney disease stages. RESULTS: Patients with lower GFR were less
      likely to present with typical chest pain. The average symptom-to-door time, door
      to-balloon time, and symptom-to-balloon time were longer with lower GFR than
      higher GFR. Primary reperfusion therapy was performed less frequently and the
      results of reperfusion therapy were poorer in patients with renal insufficiency;
      these patients were less likely to receive adjunctive medical treatment, such as
      treatment with aspirin, clopidogrel, beta-blocker, angiotensin-converting enzyme
      (ACE) inhibitor/angiotensin-receptor blocker (ARB), or statin, during
      hospitalization and at discharge. Patients who received less intense medical
      therapy had worse clinical outcomes than those who received more intense medical
      therapy. CONCLUSIONS: Patients with STEMI and renal insufficiency had less chance
      of receiving optimal medical care throughout the entire process of MI management,
      which may contribute to worse outcomes in these patients.

PMID- 22966971
TI  - Thermodynamic and kinetic hydricity of ruthenium(II) hydride complexes.
AB  - Despite the fundamental importance of the hydricity of a transition metal hydride
      (DeltaG(H-) degrees (MH) for the reaction M-H -> M+ + H-) in a range of reactions
      important in catalysis and solar energy storage, ours (J. Am. Chem. Soc.2009,
      131, 2794) are the only values reported for water solvent, and there has been no
      basis for comparison of these with the wider range already determined for
      acetonitrile solvent, in particular. Accordingly, we have used a variety of
      approaches to determine hydricity values in acetonitrile of Ru(II) hydride
      complexes previously studied in water. For [Ru(eta(6)-C6Me6)(bpy)H]+ (bpy = 2,2'
      bipyridine), we used a thermodynamic cycle based on evaluation of the acidity of
      [Ru(eta(6)-C6Me6)(bpy)H]+ pKa = 22.5 +/- 0.1 and the [Ru(eta(6)
      C6Me6)(bpy)(NCCH3)(1/0)](2+/0) electrochemical potential (-1.22 V vs Fc+/Fc). For
      [Ru(tpy)(bpy)H]+ (tpy = 2,2':6',2"-terpyridine) we utilized organic hydride ion
      acceptors (A+) of characterized hydricity derived from imidazolium cations and
      pyridinium cations, and determined K for the hydride transfer reaction, S + MH+ +
      A+ -> M(S)2+ + AH (S = CD3CN, MH+ = [Ru(tpy)(bpy)H]+), by 1H NMR measurements.
      Equilibration of initially 7 mM solutions was slow--on the time scale of a day or
      more. When E degrees (H+/H-) is taken as 79.6 kcal/mol vs Fc+/Fc as a reference,
      the hydricities of [Ru(eta(6)-C6Me6)(bpy)H]+ and [Ru(tpy)(bpy)H]+ were estimated
      as 54 +/- 2 and 39 +/- 3 kcal/mol, respectively, in acetonitrile to be compared
      with the values 31 and 22 kcal/mol, respectively, found for aqueous media. The
      pKa estimated for [Ru(tpy)(bpy)H]+ in acetonitrile is 32 +/- 3. UV-vis
      spectroscopic studies of [Ru(eta(6)-C6Me6)(bpy)]0 and [Ru(tpy)(bpy)]0 indicate
      that they contain reduced bpy and tpy ligands, respectively. These conclusions
      are supported by DFT electronic structure results. Comparison of the hydricity
      values for acetonitrile and water reveals a flattening or compression of the
      hydricity range upon transferring the hydride complexes to water.

PMID- 22966972
TI  - CD30 in myeloid malignancies: hitting the bull's-eye with an available dart.

PMID- 22966977
TI  - Endotoxin as a determinant of asthma and wheeze among rural dwelling children and
      adolescents: a case-control study.
AB  - BACKGROUND: The association between endotoxin exposure and asthma is complex and
      has been associated with rural living. We examined the relationship between
      domestic endotoxin and asthma or wheeze among rural school-aged children (6-18
      years) and assessed the interaction between endotoxin and other characteristics
      with these outcomes. METHODS: Between 2005 and 2007 we conducted a case-control
      study of children 6-18 years in the rural region of Humboldt, Canada. Cases (n =
      102) reported doctor-diagnosed asthma or wheeze in the past year. Controls (n =
      208) were randomly selected from children without asthma or wheeze. Data were
      collected to ascertain symptoms, asthma history and indoor environmental
      exposures (questionnaire), endotoxin (dust collection from the play area floor
      and child's mattress), and tobacco smoke exposure (saliva collection).
      Statistical testing was completed using multiple logistic regression to account
      for potential confounders and to assess interaction between risk factors. A
      stratified analysis was also completed to examine the effect of personal history
      of allergy. RESULTS: Among children aged 6-12 years, mattress endotoxin
      concentration (EU/mg) and load (EU/m2) were inversely associated with being a
      case [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.20-0.98; and OR =
      0.38, 95% CI = 0.20-0.75, respectively]. These associations were not observed in
      older children or with play area endotoxin. CONCLUSIONS: Our results suggest that
      endotoxin exposure might be protective for asthma or wheeze. The protective
      effect is found in younger school-aged, non-allergic children. These results may
      help explain the inconsistencies in previous studies and suggest that the
      protective effects of endotoxin in the prevention of atopy and asthma or wheeze
      are most effective earlier in life.

PMID- 22966978
TI  - Comprehensive preoperative evaluation and repair of inguinal hernias at the time
      of open radical retropubic prostatectomy decreases risk of developing post
      prostatectomy hernia.
AB  - What's known on the subject? and What does the study add? Some studies have
      evaluated preoperative and intraoperative examination for inguinal hernias and
      their repair, noting a decrease in the rate of post-prostatectomy hernias.
      However, this did not eradicate post-prostatectomy hernias, indicating that this
      method probably missed subclinical hernias. Other studies looked at prophylactic
      procedures to prevent the formation of inguinal hernias at the time of
      prostatectomy and showed a decrease in the rate of postoperative hernias. To our
      knowledge this is the only series evaluating a multi-modal approach with magnetic
      resonance imaging, ultrasonography and examination to identify all clinical and
      subclinical hernias and repair them at the time of prostatectomy. This approach
      only subjects those patients at risk for symptomatic hernias to an additional
      procedure and decreases the post-prostatectomy hernia rate to <1%. OBJECTIVE: *
      To assess if a comprehensive evaluation to diagnose clinical and subclinical
      hernias and repair of these hernias at the time of open radical retropubic
      prostatectomy (ORRP) decreases the incidence of clinical inguinal hernias (IHs)
      after ORRP. PATIENTS AND METHODS: * Between 1 July 2007 and 31 July 2010, 281
      consecutive men underwent ORRP by a single surgeon. * Of these men, 207 (74%)
      underwent comprehensive preoperative screening for IH, which included physical
      examination, upstanding ultrasonography and magnetic resonance imaging. * Between
      12 and 24 months after ORRP, 178 (86%) of these men completed a questionnaire
      designed to capture development of clinical IHs. RESULTS: * Of the 178 evaluable
      patients, 92 (52%) were diagnosed preoperatively with IH by at least one
      diagnostic modality. * Forty-one and 51 of the men had bilateral or unilateral
      IHs, respectively for a total of 133 IHs. * No preoperative factor was
      significantly associated with the presence of an IH before prostatectomy. * No
      groin subjected to IH repair (IHR) at the time of ORRP developed a clinical IH
      compared with four of the 21 patients with postoperative IHs who did not undergo
      repair of their preoperatively diagnosed IH at the time of ORRP (P= 0.024). *
      Only one (0.4%) clinical IH developed in a groin that had no evidence of IH by
      physical examination, upstanding ultrasonography and magnetic resonance imaging
      before prostatectomy. CONCLUSIONS: * Our comprehensive evaluation increases the
      detection of IHs before ORRP. * Repair of these IHs at the time of ORRP
      significantly decreases the risk of developing post-prostatectomy clinical IHs.

PMID- 22966979
TI  - An unusual case of retrovesical ectopic prostate tissue accompanied by primary
      prostate cancer.
AB  - We report an unusual case of retrovesical ectopic prostate tissue in a 73-year
      old man with primary prostate cancer. The man's prostate-specific antigen was
      24.66 ng/ml.Transabdominal ultrasonography, pelvic computed tomography,and pelvic
      magnetic resonance imaging demonstrated a heterogeneous 8.5 * 8.0 * 7.0 cm mass
      in contact with the posterior wall of the urinary bladder. The patient underwent
      a retropubic radical prostatectomy and resection of tumor. Pathological
      examination of prostate revealed a prostatic adenocarcinoma, Gleason score of 4 +
      5 = 9, and the retrovesical tumor was confirmed to be a benign prostate tissue.

PMID- 22966980
TI  - Protein-DNA docking with a coarse-grained force field.
AB  - BACKGROUND: Protein-DNA interactions are important for many cellular processes,
      however structural knowledge for a large fraction of known and putative complexes
      is still lacking. Computational docking methods aim at the prediction of complex
      architecture given detailed structures of its constituents. They are becoming an
      increasingly important tool in the field of macromolecular assemblies,
      complementing particularly demanding protein-nucleic acids X ray crystallography
      and providing means for the refinement and integration of low resolution data
      coming from rapidly advancing methods such as cryoelectron microscopy. RESULTS:
      We present a new coarse-grained force field suitable for protein-DNA docking. The
      force field is an extension of previously developed parameter sets for protein
      RNA and protein-protein interactions. The docking is based on potential energy
      minimization in translational and orientational degrees of freedom of the binding
      partners. It allows for fast and efficient systematic search for native-like
      complex geometry without any prior knowledge regarding binding site location.
      CONCLUSIONS: We find that the force field gives very good results for bound
      docking. The quality of predictions in the case of unbound docking varies,
      depending on the level of structural deviation from bound geometries. We analyze
      the role of specific protein-DNA interactions on force field performance, both
      with respect to complex structure prediction, and the reproduction of
      experimental binding affinities. We find that such direct, specific interactions
      only partially contribute to protein-DNA recognition, indicating an important
      role of shape complementarity and sequence-dependent DNA internal energy, in line
      with the concept of indirect protein-DNA readout mechanism.

PMID- 22966981
TI  - Design, synthesis, and structure-activity relationship of N-arylnaphthylamine
      derivatives as amyloid aggregation inhibitors.
AB  - Dyes like CR are able to inhibit the aggregation of Abeta fibrils. Thus, a
      screening of a series of dyes including ABBB (1) was performed. Its main
      component 2 tested in an in vitro assay (i.e., ThT assay) showed good potency at
      inhibiting fibrils association. Congeners 4-9 have been designed and synthesized
      as inhibitors of Abeta aggregation. A number of these newly synthesized compounds
      have been found to be active in the ThT assay with IC(50) of 1-57.4 MUM. The most
      potent compound of this series, 4k, showed micromolar activity in this test.
      Another potent derivative 4q (IC(50) = 5.6 MUM) rapidly crossed the blood-brain
      barrier, achieving whole brain concentrations higher than in plasma. So 4q could
      be developed to find novel potent antiaggregating betaA agents useful in
      Alzheimer disease as well as other neurological diseases characterized by
      deposits of amyloid aggregates.

PMID- 22966982
TI  - Molecular organization, biochemical function, cellular role and evolution of
      NfuA, an atypical Fe-S carrier.
AB  - Biosynthesis of iron-sulphur (Fe-S) proteins is catalysed by multi-protein
      systems, ISC and SUF. However, 'non-ISC, non-SUF' Fe-S biosynthesis factors have
      been described, both in prokaryotes and eukaryotes. Here we report in vitro and
      in vivo investigations of such a 'non-ISC, non SUF' component, the Nfu proteins.
      Phylogenomic analysis allowed us to define four subfamilies. Escherichia coli
      NfuA is within subfamily II. Most members of this subfamily have a Nfu domain
      fused to a 'degenerate' A-type carrier domain (ATC*) lacking Fe-S cluster co
      ordinating Cys ligands. The Nfu domain binds a [4Fe-4S] cluster while the ATC*
      domain interacts with NuoG (a complex I subunit) and aconitase B (AcnB). In
      vitro, holo-NfuA promotes maturation of AcnB. In vivo, NfuA is necessary for full
      activity of complex I under aerobic growth conditions, and of AcnB in the
      presence of superoxide. NfuA receives Fe-S clusters from IscU/HscBA and SufBCD
      scaffolds and eventually transfers them to the ATCs IscA and SufA. This study
      provides significant information on one of the Fe-S biogenesis factors that has
      been often used as a building block by ISC and/or SUF synthesizing organisms,
      including bacteria, plants and animals.

PMID- 22966983
TI  - Importance of superior vena cava isolation in successful ablation of persistent
      atrial fibrillation in patient with partial anomalous pulmonary vein.
AB  - Ectopic foci arising from pulmonary veins (PVs) are the predominant sources for
      the initiation and maintenance of atrial fibrillation (AF) in a vast majority of
      cases. However, ectopic foci also exist in the non-PV areas like superior vena
      cava (SVC) in 10-20% of the cases. We report the significance of SVC isolation in
      a patient with persistent AF and anomalous pulmonary venous connection of the
      right superior pulmonary vein into the SVC.

PMID- 22966984
TI  - Magnetic ionic liquids produced by the dispersion of magnetic nanoparticles in 1
      n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2).
AB  - This paper reports on the advancement of magnetic ionic liquids (MILs) as stable
      dispersions of surface-modified gamma-Fe(2)O(3), Fe(3)O(4), and CoFe(2)O(4)
      magnetic nanoparticles (MNPs) in a hydrophobic ionic liquid, 1-n-butyl 3
      methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf(2)). The MNPs were
      obtained via coprecipitation and were characterized using powder X-ray
      diffraction, transmission electron microscopy, Raman spectroscopy and Fourier
      transform near-infrared (FT-NIR) spectroscopy, and magnetic measurements. The
      surface-modified MNPs (SM-MNPs) were obtained via the silanization of the MNPs
      with the aid of 1-butyl-3-[3-(trimethoxysilyl)propyl]imidazolium chloride
      (BMSPI.Cl). The SM-MNPs were characterized by Raman spectroscopy and Fourier
      transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy and by
      magnetic measurements. The FTIR-ATR spectra of the SM-MNPs exhibited
      characteristic absorptions of the imidazolium and those of the Fe-O-Si-C
      moieties, confirming the presence of BMSPI.Cl on the MNP surface.
      Thermogravimetric analysis (TGA) showed that the SM-MNPs were modified by at
      least one BMSPI.Cl monolayer. The MILs were characterized using Raman
      spectroscopy, differential scanning calorimetry (DSC), and magnetic measurements.
      The Raman and DSC results indicated an interaction between the SM-MNPs and the
      IL. This interaction promotes the formation of a supramolecular structure close
      to the MNP surface that mimics the IL structure and is responsible for the
      stability of the MIL. Magnetic measurements of the MILs indicated no hysteresis.
      Superparamagnetic behavior and a saturation magnetization of ~22 emu/g could be
      inferred from the magnetic measurements of a sample containing 50% w/w gamma
      Fe(2)O(3) SM-MNP/BMI.NTf(2).

PMID- 22966985
TI  - IL-6 deficiency exacerbates skin inflammation in a murine model of irritant
      dermatitis.
AB  - Contact dermatitis is the second most reported occupational injury associated
      with workers compensation. Inflammatory cytokines are closely involved with the
      development of dermatitis, and their modulation could exacerbate skin damage,
      thus contributing to increased irritancy. IL-6 is a pro-inflammatory cytokine
      paradoxically associated with both skin healing and inflammation. To determine
      what role this pleiotropic cytokine plays in chemically-induced irritant
      dermatitis, IL-6 deficient (KO), IL-6 over-expressing transgenic (TgIL6), and
      corresponding wild-type (WT) mice were exposed to acetone or the irritants JP-8
      jet fuel or benzalkonium chloride (BKC) daily for 7 days. Histological analysis
      of exposed skin was performed, as was tissue mRNA and protein expression patterns
      of inflammatory cytokines via QPCR and multiplex ELISA. The results indicated
      that, following JP-8 exposure, IL-6KO mice had greatly increased skin IL-1beta,
      TNFalpha, CCL2, CCL3, and CXCL1 mRNA and corresponding product protein expression
      when compared to that of samples from WT counterparts and acetone-exposed control
      mice. BKC treatment induced the expression of all cytokines examined as compared
      to acetone, with CCL2 significantly higher in skin from IL-6KO mice. Histological
      analysis showed that IL-6KO mice displayed significantly more inflammatory cell
      infiltration as compared to WT and TgIL6 mice in response to jet fuel. Analysis
      of mRNA for the M2 macrophage marker CD206 indicated a 4-fold decrease in skin of
      IL-6KO mice treated with either irritant as compared to WT. Taken together, these
      observations suggest that IL-6 acts in an anti-inflammatory manner during
      irritant dermatitis, and these effects are dependent on the chemical nature of
      the irritant.

PMID- 22966986
TI  - Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy
      volunteers: pharmacokinetic/ pharmacodynamic analysis of three phase 1 trials.
AB  - AIM: To characterize quantitatively the relationship between ABT-102, a potent
      and selective TRPV1 antagonist, exposure and its effects on body temperature in
      humans using a population pharmacokinetic/pharmacodynamic modelling approach.
      METHODS: Serial pharmacokinetic and body temperature (oral or core) measurements
      from three double-blind, randomized, placebo-controlled studies [single dose (2,
      6, 18, 30 and 40 mg, solution formulation), multiple dose (2, 4 and 8 mg twice
      daily for 7 days, solution formulation) and multiple-dose (1, 2 and 4 mg twice
      daily for 7 days, solid dispersion formulation)] were analyzed. NONMEM was used
      for model development and the model building steps were guided by pre-specified
      diagnostic and statistical criteria. The final model was qualified using non
      parametric bootstrap and visual predictive check. RESULTS: The developed body
      temperature model included additive components of baseline, circadian rhythm
      (cosine function of time) and ABT-102 effect (Emax function of plasma
      concentration) with tolerance development (decrease in ABT-102 Emax over time).
      Type of body temperature measurement (oral vs. core) was included as a fixed
      effect on baseline, amplitude of circadian rhythm and residual error. The model
      estimates (95% bootstrap confidence interval) were: baseline oral body
      temperature, 36.3 (36.3, 36.4) degrees C; baseline core body temperature, 37.0
      (37.0, 37.1) degrees C; oral circadian amplitude, 0.25 (0.22, 0.28) degrees C;
      core circadian amplitude, 0.31 (0.28, 0.34) degrees C; circadian phase shift, 7.6
      (7.3, 7.9) h; ABT-102 Emax , 2.2 (1.9, 2.7) degrees C; ABT-102 EC50 , 20 (15, 28)
      ng ml(-1) ; tolerance T50 , 28 (20, 43) h. CONCLUSIONS: At exposures predicted to
      exert analgesic activity in humans, the effect of ABT-102 on body temperature is
      estimated to be 0.6 to 0.8 degrees C. This effect attenuates within 2 to 3 days
      of dosing.

PMID- 22966987
TI  - The feasibility of multiparametric magnetic resonance imaging for targeted biopsy
      using novel navigation systems to detect early stage prostate cancer: the
      preliminary experience.
AB  - BACKGROUND AND PURPOSE: The feasibility and diagnostic performance of
      multiparametric magnetic resonance imaging (mp-MRI) has to be proven further. In
      this study, we evaluate the role of mp-MRI for targeted biopsy of early stage
      prostate cancer (PCa). PATIENTS AND METHODS: A total 32 consecutive patients with
      transrectal ultrasonography (TRUS)-guided biopsy-proven PCa meeting low-risk
      criteria and pursuing active surveillance were selected to undergo mp-MRI 3 Tesla
      (3T) with endorectal coil. Patients were divided then into three groups based on
      the method used to target the mp-MRI designated region of interest (ROI): Group 1
      underwent TRUS-guided prostate biopsy using an MRI-based coordinate plan
      (cognitive targeting). Group 2 underwent MRI-targeted TRUS-guided prostate biopsy
      using MyLabTMTwice, which superimposed the archived MRI images onto the real-time
      ultrasonography image allowing targeted biopsy of the ROI (fusion targeting).
      Group 3 included selected patients who had an elevation in prostate-specific
      antigen levels, or patients followed after radiation therapy (two patients) for
      suspicious unifocal MRI lesion recurrence. These patients underwent MRI-guided
      biopsy of the suspicious ROI using the navigation system DynaTRIM. RESULTS: The
      cancer detection rate in group 1 was 33.3% (3 of 10 patients), while in group 2,
      it was significantly higher at 46.2%. The sensitivity and specificity for group 1
      was 45.5% and 33.3%, vs 61.9% and 20.8% in group 2, respectively. The positive
      predictive value in group 1 was 50.0% vs 53.8% in group 2 (P=0.04). In group 3,
      the cancer detection rate was much higher (80%) than in group 2, (P=0.005)
      although the majority of these patients (7 of 10) had a previously diagnosed
      prostate cancer on TRUS-guided 12-core biopsy. CONCLUSION: Our preliminary
      experience of mp-MRI suggests the detection of early stage prostate cancer with
      low-risk features yields potential candidates for active surveillance or focal
      targeted therapy. The MRI-TRUS fusion system increases diagnostic yield compared
      with cognitive MRI-directed TRUS-guided biopsy.

PMID- 22966988
TI  - Port-a-Cath-related complications in 252 patients with solid tissue tumours and
      the first report of heparin-induced delayed hypersensitivity after Port-a-Cath
      heparinisation.
AB  - The use of the subcutaneous Port-a-Catheters (Port-a-Caths) provides an important
      mean of venous access for oncological patients. The aim of our retrospective
      consecutive single-centre study was to investigate Port-a-Cath-related
      complications in 252 cancer patients. Overall period of Port-a-Caths maintenance
      was 25 months. The strategy of our centre is to keep Port-a-Caths in situ up to
      the end of follow-up in adjuvant cancer patients. A total of 22 complications
      were recorded (8.73%). Interventional complications occurred in four patients.
      The main complications during Port-a-Cath use included thrombosis (4 patients,
      1.58%), infections (4 patients, 1.58%), persistent pain or discomfort (3
      patients, 1.19%) and dislocations (2 patients, 0.79%). Median time to the
      occurrence of any type of complications was 4.5 months. Eleven Port-a-Caths were
      removed due to complications (4.36%). Similar rate of Port-a-Cath-related
      thrombosis/infection was seen in adjuvant and advanced cancer patients (no
      statistical significance). Continuous infusion of anticancer therapy via a Port-a
      Cath system is a relatively safe procedure, although major complications might
      occur. We are first to describe heparin-induced delayed hypersensitivity after
      heparinisation of Port-a-Cath. This fact should influence the preference to keep
      the Port-a-Cath after completion of adjuvant anticancer treatment.

PMID- 22966989
TI  - Central poststroke pain: somatosensory abnormalities and the presence of
      associated myofascial pain syndrome.
AB  - BACKGROUND: Central post-stroke pain (CPSP) is a neuropathic pain syndrome
      associated with somatosensory abnormalities due to central nervous system lesion
      following a cerebrovascular insult. Post-stroke pain (PSP) refers to a broader
      range of clinical conditions leading to pain after stroke, but not restricted to
      CPSP, including other types of pain such as myofascial pain syndrome (MPS),
      painful shoulder, lumbar and dorsal pain, complex regional pain syndrome, and
      spasticity-related pain. Despite its recognition as part of the general PSP
      diagnostic possibilities, the prevalence of MPS has never been characterized in
      patients with CPSP patients. We performed a cross-sectional standardized clinical
      and radiological evaluation of patients with definite CPSP in order to assess the
      presence of other non-neuropathic pain syndromes, and in particular, the role of
      myofascial pain syndrome in these patients. METHODS: CPSP patients underwent a
      standardized sensory and motor neurological evaluation, and were classified
      according to stroke mechanism, neurological deficits, presence and profile of
      MPS. The Visual Analogic Scale (VAS), McGill Pain Questionnaire (MPQ), and Beck
      Depression Scale (BDS) were filled out by all participants. RESULTS: Forty CPSP
      patients were included. Thirty-six (90.0%) had one single ischemic stroke. Pain
      presented during the first three months after stroke in 75.0%. Median pain
      intensity was 10 (5 to 10). There was no difference in pain intensity among the
      different lesion site groups. Neuropathic pain was continuous-ongoing in 34
      (85.0%) patients and intermittent in the remainder. Burning was the most common
      descriptor (70%). Main aggravating factors were contact to cold (62.5%). Thermo
      sensory abnormalities were universal. MPS was diagnosed in 27 (67.5%) patients
      and was more common in the supratentorial extra-thalamic group (P <0.001). No
      significant differences were observed among the different stroke location groups
      and pain questionnaires and scales scores. Importantly, CPSP patients with and
      without MPS did not differ in pain intensity (VAS), MPQ or BDS scores.
      CONCLUSIONS: The presence of MPS is not an exception after stroke and may present
      in association with CPSP as a common comorbid condition. Further studies are
      necessary to clarify the role of MPS in CPSP.

PMID- 22966990
TI  - Dynamic spreading of nanofluids on solids. Part I: experimental.
AB  - Nanofluids have enhanced thermophysical properties compared to fluids without
      nanoparticles. Recent experiments have clearly shown that the presence of
      nanoparticles enhances the spreading of nanofluids. We report here the results of
      our experiments on the spreading of nanofluids comprising 5, 10, and 20 vol %
      silica suspensions of 19 nm particles displacing a sessile drop placed on a glass
      surface. The contact line position is observed from both the top and side views
      simultaneously using an advanced optical technique. It is found that the
      nanofluid spreads, forming a thin nanofluid film between the oil drop and the
      solid surface, which is seen as a bright inner contact line distinct from the
      conventional three-phase outer contact line. For the first time, the rate of the
      nanofluidic film spreading is experimentally observed as a function of the
      nanoparticle concentration and the oil drop volume. The speed of the inner
      contact line is seen to increase with an increase in the nanoparticle
      concentration and decrease with a decrease in the drop volume, that is, with an
      increase in the capillary pressure. Interestingly, the formation of the inner
      contact line is not seen in fluids without nanoparticles.

PMID- 22966992
TI  - Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis
      and non-alcoholic steatohepatitis distinct conditions?
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently conceptualised
      as a clinical spectrum that results from a 'multiple-hit' process which begins
      with simple steatosis and subsequently renders the hepatocytes susceptible to a
      variety of insults. Ultimately, more serious liver injuries like non-alcoholic
      steatohepatitis (NASH) and cirrhosis may develop. Although the metabolic syndrome
      is considered the crucial player in the pathogenesis of NAFLD, recent studies
      have highlighted novel pathophysiological mechanisms in this clinical entity.
      AIM: To discuss the pathophysiology of NAFLD based on the hypothesis that simple
      steatosis and NASH are discrete entities rather than two points on a spectrum.
      METHODS: A literature search was conducted in August 2012 on PubMed, Ovid Embase,
      Ovid Medline and Scopus using the following search terms: steatosis, non
      alcoholic steatohepatitis, pathophysiology, fatty liver, natural history and
      genetics. RESULTS: Simple steatosis and NASH appear as two distinct
      pathophysiological entities and progression from pure fatty liver to NASH appears
      to be so rare as to warrant publication. The possible pathogenetic pathways
      specifically related to NASH are highlighted. CONCLUSIONS: Although simple
      steatosis and non-alcoholic steatohepatitis are currently viewed as two
      histological subtypes of the unique spectrum of non-alcoholic fatty liver
      disease, the two conditions are likely distinct not only from a histological but
      also from a pathophysiological standpoint. Efforts to distinguish simple
      steatosis from non-alcoholic steatohepatitis using non-invasive modalities should
      be informed by the current pathophysiology of these two clinical entities.

PMID- 22966991
TI  - Enhanced depolarization-induced pulmonary vasoconstriction following chronic
      hypoxia requires EGFR-dependent activation of NAD(P)H oxidase 2.
AB  - AIMS: Chronic hypoxia (CH) enhances depolarization-induced myofilament Ca(2+)
      sensitization and resultant pulmonary arterial constriction through superoxide
      (O(2)(-))-dependent stimulation of RhoA. Because NAD(P)H oxidase (NOX) has been
      implicated in the development of pulmonary hypertension, we hypothesized that
      vascular smooth muscle (VSM) depolarization increases NOX-derived O(2)(-)
      production leading to myofilament Ca(2+) sensitization and augmented
      vasoconstrictor reactivity following CH. As epidermal growth factor receptor
      (EGFR) mediates Rac1-dependent NOX activation in renal mesangial cells, we
      further sought to examine the role EGFR plays in this response. RESULTS:
      Vasoconstrictor responses to depolarizing concentrations of KCl were greater in
      lungs isolated from CH (4 wk, 0.5 atm) rats compared to normoxic controls, and
      this effect of CH was abolished by the general NOX inhibitor, apocynin. CH
      similarly augmented KCl-induced vasoconstriction and O(2)(-) generation (assessed
      using the fluorescent indicator, dihydroethidium) in Ca(2+)-permeabilized,
      pressurized small pulmonary arteries. These latter responses to CH were prevented
      by general inhibition of NOX isoforms (apocynin, diphenylene iodonium), and by
      selective inhibition of NOX 2 (gp91ds-tat), Rac1 (NSC 23766), and EGFR (AG 1478).
      Consistent with these observations, CH increased KCl-induced EGFR
      phosphorylation, and augmented depolarization-induced Rac1 activation in an EGFR
      dependent manner. INNOVATION: This study establishes a novel signaling axis in
      VSM linking membrane depolarization to contraction that is independent of Ca(2+)
      influx, and which mediates myofilament Ca(2+) sensitization in the hypertensive
      pulmonary circulation. CONCLUSION: CH augments membrane depolarization-induced
      pulmonary VSM Ca(2+) sensitization and vasoconstriction through EGFR-dependent
      stimulation of Rac1 and NOX 2.

PMID- 22966993
TI  - Big lie, small world: what E. Lynn Harris wanted readers to understand about the
      struggle for African American, homosexual males seeking to attain the American
      dream.
AB  - This article will examine the social implications for African American homosexual
      males seeking to achieve the American Dream. Invisible Life and Just as I Am-the
      first two novels in a trilogy by the late E. Lynn Harris writing from a semi
      autobiographical perspective in late-twentieth century America-will serve as the
      texts that drive this research topic. Careful analysis of these works will
      substantiate the assertion that the American Dream, even on the cusp of the new
      millennium, is just beyond the grasp of this specific subpopulation.

PMID- 22966994
TI  - Confronting hate: heterosexuals' responses to anti-gay comments.
AB  - An online diary study was used to examine the individual and situational
      variables that influence non-targets' verbal and nonverbal reactions and
      responses to sexually prejudiced remarks. Results indicated that anti-gay
      comments were extremely prevalent in a college setting and resulted in a range of
      reactions and behaviors. Confrontation of the perpetrator was predicted by the
      perceived offensiveness of the comment, perceived social pressure to confront,
      and the number of close same-sex attracted friends. Additionally, those who
      confronted felt more satisfied with their responses than those who did not
      confront. Implications for future research and prejudice reduction strategies are
      discussed.

PMID- 22966995
TI  - From Chavela to Frida: loving from the margins.
AB  - This article analyzes the portrayal of lesbian desire in the case of two of the
      most renowned icons of contemporary Mexican and Latino popular culture: singer
      Chavela Vargas (1919-2012) and painter Frida Kahlo (1910-1954). This article
      explores the intertextual dialogue between two texts that deal with the
      construction of Kahlo's persona and sexuality: Chavela's memoir, titled Y si
      quieres saber de mi pasado (2002), and the film Frida (2001), directed by Julie
      Taymor. Fundamental to this study is Chavela Vargas' lesbian subject position in
      both texts and the consequences and implications her location has in representing
      lesbian homoerotics and desire.

PMID- 22966996
TI  - Gay officers in their midst: heterosexual police employees' anticipation of the
      consequences for coworkers who come out.
AB  - While fear among gay men and lesbians about being out in a masculinist
      environment is not surprising, this article examines what heterosexuals expect
      will happen when gay men and lesbians come out. We draw on a unique dataset from
      a police department in the southwest United States to examine the consequences
      anticipated by heterosexual police department employees if a gay or lesbian
      officer's sexual orientation became known in the workplace. We test four main
      sets of factors: individual-level demographic characteristics and religious
      background; homophobia; organizational tolerance for discrimination; and
      intergroup contact theory to explain how heterosexuals expect gay and lesbian
      coworkers to be treated. Using ordinary least squares regression, we find that
      characteristics of workplaces, measured by tolerance of discrimination, as well
      as contact with gay men and lesbians on the job are more significant predictors
      of anticipated outcomes than are individual-level traits and homophobic
      attitudes. We conclude by discussing the policy implications of our research.

PMID- 22966997
TI  - Exploring relationships between sexual orientation and satisfaction with faculty
      and staff interactions.
AB  - Lesbian, gay, and bisexual (LGB) students are a unique population within colleges
      and universities, yet, few studies have sought to uncover the distinctive
      environmental influences and background characteristics that foster their
      satisfaction. The purpose of this study was to examine the relationship between
      sexual orientation and a sense of satisfaction with faculty and staff
      interactions among undergraduate students. Analysis of variance results indicated
      that LGB students, on average, reported significantly higher satisfaction with
      faculty and staff interactions than heterosexual students. Using  Astin's (1993 )
      input-environments-outcome model as a conceptual framework, the hierarchical
      regression analysis yielded numerous significant variables as predictors for
      student satisfaction with faculty and staff interactions.

PMID- 22966998
TI  - Measure of internalized sexual stigma for lesbians and gay men: a new scale.
AB  - The goal of this study is to propose a new Measure of Internalized Sexual Stigma
      for Lesbians and Gay Men (MISS-LG) that assesses three dimensions of internalized
      homonegativity: identity, social discomfort, and sexuality. A convenience sample
      of 735 Italian lesbians and gay male participants was used to demonstrate the
      psychometric validity of the scale. Results of confirmatory factor analysis
      supported three identifiable factors reflecting theoretically based constructs of
      the MISS-LG. The correlations with other instruments demonstrate the convergent
      validity: lesbian and gay participants with high internalized sexual stigma
      describe lower levels of self-disclosure and wellbeing. Implications for research
      and practice are discussed.

PMID- 22966999
TI  - Orthogonally functionalized naphthodithiophenes: selective protection and
      borylation.
AB  - Selective functionalization protocols of naphtho[1,2-b;5,6-b']dithiophene (NDT3)
      by combining protection of the thiophene alpha-positions and direct borylation on
      the naphthalene core are described, which allows synthesizing a number of new
      NDT3-based building blocks with various substituents and isomeric NDT3-based
      polymers with different main chain structures. The same protocol is applicable to
      other isomeric naphthodithiophenes (NDTs), which affords a set of key building
      blocks for the development of elaborated functional pi-materials.

PMID- 22967001
TI  - Personality of outpatients with malignant tumors: a cross-sectional study.
AB  - BACKGROUND: There have been scarce large-scale studies investigating the
      personality of patients with malignant tumors. The purpose of this study is to
      determine the characteristic personality in malignant tumors outpatients.
      METHODS: Three thousand and three among 5013 consecutive outpatients who
      consented to answer the Japanese Maudsley Personality Inventory questionnaires
      were divided into two groups. 603 outpatients diagnosed with malignant tumors (M
      group) and the other 2400 outpatients (non-M group) were enrolled in this study.
      We determined three scores such as introversion/extroversion (E-score),
      neuroticism (N-score), and lie detection (L-score). All data were used to compare
      the two groups. RESULTS: Average E-score was slightly higher, and average N-score
      was slightly lower in M group than that in non-M group, and no significant
      differences between the two groups. However, the average L-score in M group was
      significant higher than that in non-M group (p < 0.01). CONCLUSION: Outpatients
      with malignant tumors showed a significantly higher L-score on MPI when compared
      with patients with non-malignant tumors. These results stress the importance of
      taking the mentality of patients with cancer into consideration when conducting
      treatment and care.

PMID- 22967002
TI  - Radiotherapy in orbital lymphoma: optimizing the backbone to build upon.

PMID- 22967000
TI  - Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and
      osteogenesis.
AB  - BACKGROUND: Many growth factors, such as bone morphogenetic protein (BMP)-2, have
      been shown to interact with polymers of sulfated disacharrides known as heparan
      sulfate (HS) glycosaminoglycans (GAGs), which are found on matrix and cell
      surface proteoglycans throughout the body. HS GAGs, and some more highly sulfated
      forms of chondroitin sulfate (CS), regulate cell function by serving as co
      factors, or co-receptors, in GF interactions with their receptors, and HS or CS
      GAGs have been shown to be necessary for inducing signaling and GF activity, even
      in the osteogenic lineage. Unlike recombinant proteins, however, HS and CS GAGs
      are quite heterogenous due, in large part, to post-translational addition, then
      removal, of sulfate groups to various positions along the GAG polymer. We have,
      therefore, investigated whether it would be feasible to deliver a DNA pro-drug to
      generate a soluble HS/CS proteoglycan in situ that would augment the activity of
      growth-factors, including BMP-2, in vivo. RESULTS: Utilizing a purified
      recombinant human perlecan domain 1 (rhPln.D1) expressed from HEK 293 cells with
      HS and CS GAGs, tight binding and dose-enhancement of rhBMP-2 activity was
      demonstrated in vitro. In vitro, the expressed rhPln.D1 was characterized by
      modification with sulfated HS and CS GAGs. Dose-enhancement of rhBMP-2 by a
      pln.D1 expression plasmid delivered together as a lyophilized single-phase on a
      particulate tricalcium phosphate scaffold for 6 or more weeks generated up to 9
      fold more bone volume de novo on the maxillary ridge in a rat model than in
      control sites without the pln.D1 plasmid. Using a significantly lower BMP-2 dose,
      this combination provided more than 5 times as much maxillary ridge augmentation
      and greater density than rhBMP-2 delivered on a collagen sponge (InFuseTM).
      CONCLUSIONS: A recombinant HS/CS PG interacted strongly and functionally with BMP
      2 in binding and cell-based assays, and, in vivo, the pln.247 expression plasmid
      significantly improved the dose-effectiveness of BMP-2 osteogenic activity for in
      vivo de novo bone generation when delivered together on a scaffold as a single
      phase. The use of HS/CS PGs may be useful to augment GF therapeutics, and a
      plasmid-based approach has been shown here to be highly effective.

PMID- 22967003
TI  - Comprehensive preoperative evaluation and repair of inguinal hernias at the time
      of open radical retropubic prostatectomy decreases risk of developing
      postprostatectomy hernia.

PMID- 22967005
TI  - Automated diagnosis of epilepsy using EEG power spectrum.
AB  - Interictal electroencephalography (EEG) has clinically meaningful limitations in
      its sensitivity and specificity in the diagnosis of epilepsy because of its
      dependence on the occurrence of epileptiform discharges. We have developed a
      computer-aided diagnostic (CAD) tool that operates on the absolute spectral
      energy of the routine EEG and has both substantially higher sensitivity and
      negative predictive value than the identification of interictal epileptiform
      discharges. Our approach used a multilayer perceptron to classify 156 patients
      admitted for video-EEG monitoring. The patient population was diagnostically
      diverse; 87 were diagnosed with either generalized or focal seizures. The
      remainder of the patients were diagnosed with nonepileptic seizures. The
      sensitivity was 92% (95% confidence interval [CI] 85-97%) and the negative
      predictive value was 82% (95% CI 67-92%). We discuss how these findings suggest
      that this CAD can be used to supplement event-based analysis by trained
      epileptologists.

PMID- 22967004
TI  - Bacterial modulation of human fetal membrane Toll-like receptor expression.
AB  - PROBLEM: Preterm premature rupture of fetal membranes (pPROM) occurs in 30-40% of
      spontaneous preterm births (PTB) and is associated with intra-amniotic infection
      and inflammation. The membranes may sense and respond to microbes via Toll-like
      receptors (TLRs); however, little is known about their expression and regulation
      in this tissue. The objective of this study was to evaluate the expression of
      TLRs 1-10 in fetal membranes after exposure to pathogens associated with intra
      amniotic infection and PTB. METHOD OF STUDY: Normal human term fetal membrane
      explants were exposed to various bacteria. After 24 hrs, RNA was extracted and
      quantitative RT-PCR performed for TLRs1-10. RESULTS: Treatment of fetal membranes
      with Mycoplasma hominis increased expression of TLR4, TLR6, and TLR8 mRNA.
      Ureaplasma parvum upregulated TLR8 mRNA, and Porphyromonas gingivalis
      significantly increased fetal membrane TLR7 expression. In contrast, treatment
      with Gram-negative Escherichia coli (and its cell wall component
      lipopolysaccharide) downregulated TLR10 mRNA. No effect was detected for
      Ureaplasma urealyticum, Gardnerella vaginalis, or Group B Streptococcus.
      CONCLUSION: These findings demonstrate that different types of bacteria have
      distinct effects on fetal membrane TLR expression patterns. Moreover, these
      findings highlight the disparity of fetal membrane responses to infection and
      thus suggest heterogeneity in the mechanisms by which infection-associated
      pregnancy complications, such as pPROM and PTB, arise.

PMID- 22967006
TI  - Interactions between superficial and deep dorsal horn spinal cord neurons in the
      processing of nociceptive information.
AB  - In acute rat spinal cord slices, the application of capsaicin (5 MUm, 90 s), an
      agonist of transient receptor potential vanilloid 1 receptors expressed by a
      subset of nociceptors that project to laminae I-II of the spinal cord dorsal
      horn, induced an increase in the frequency of spontaneous excitatory and
      spontaneous inhibitory postsynaptic currents in about half of the neurons in
      laminae II, III-IV and V. In the presence of tetrodotoxin, which blocks action
      potential generation and polysynaptic transmission, capsaicin increased the
      frequency of miniature excitatory postsynaptic currents in only 30% of lamina II
      neurons and had no effect on the frequency of miniature excitatory postsynaptic
      currents in laminae III-V or on the frequency of miniature inhibitory
      postsynaptic currents in laminae II-V. When the communication between lamina V
      and more superficial laminae was interrupted by performing a mechanical section
      between laminae IV and V, capsaicin induced an increase in spontaneous excitatory
      postsynaptic current frequency in laminae II-IV and an increase in spontaneous
      inhibitory postsynaptic current frequency in lamina II that were similar to those
      observed in intact slices. However, in laminae III-IV of transected slices, the
      increase in spontaneous inhibitory postsynaptic current frequency was virtually
      abolished. Our results indicate that nociceptive information conveyed by
      transient receptor potential vanilloid 1-expressing nociceptors is transmitted
      from lamina II to deeper laminae essentially by an excitatory pathway and that
      deep laminae exert a 'feedback' control over neurons in laminae III-IV by
      increasing inhibitory synaptic transmission in these laminae. Moreover, we
      provide evidence that laminae III-IV might play an important role in the
      processing of nociceptive information in the dorsal horn.

PMID- 22967007
TI  - Hispolon attenuates balloon-injured neointimal formation and modulates vascular
      smooth muscle cell migration via AKT and ERK phosphorylation.
AB  - The pathological mechanism of restenosis is attributed primarily to excessive
      proliferation and migration of vascular smooth muscle cells (VSMC). The
      preventive effects of hispolon (1) on balloon injury-induced neointimal formation
      were investigated, and 1 showed potent activity in inhibiting fetal bovine serum
      induced VSMC outgrowth. Hispolon (1) significantly inhibited VSMC migration, as
      shown by trans-well assays. Compound 1 decreased the expression and secretion of
      matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The
      expression of the endogenous inhibitors of these proteins, namely, tissue
      inhibitors of MMP (TIMP-1 and TIMP-2), increased. The inhibition by noncytotoxic
      doses of 1 of VSMC migration was through its negative regulatory effects on FAK
      phosphorylation, ERK1/2 phosphorylation, and PI3K/AKT. These results demonstrate
      that 1 can inhibit the migration of VSMC by reduced expression of MMP-9 through
      the suppression of the FAK signaling pathway and of the activity of PI3K/AKT. The
      data obtained suggest that 1 might block balloon injury-induced neointimal
      hyperplasia via the inhibition of VSMC proliferation and migration, without
      inducing apoptosis.

PMID- 22967008
TI  - Visceral pain readouts in experimental medicine.
AB  - Visceral pain is studied at the level of the primary afferent fiber, spinal cord,
      subcortical, and cortical levels electrophysiologically and using brain imaging,
      which provides an objective measure of excitation at each level. However,
      correlation of these with actual perception of pain in conscious animal models
      has been problematic, and we rely on indirect measures in most preclinical
      research. The main method is electromyographic recording of abdominal muscle
      contractions in response to colorectal distension (CRD), which may reflect
      reflexes set up at several levels of the above pathway. Several experimental
      treatments for visceral pain have failed in clinical trials, possibly because of
      failure to translate from preclinical observations on CRD responses in animals to
      perception of spontaneous events in patients. Therefore, we need more objective
      outcomes. In this NGM issue, Hultin et al. show feasibility of routine recordings
      of cortical evoked electrical potentials (CEP) using implanted cranial electrodes
      in response to graded CRD in rats. CEP comprised three temporal components with
      latencies of approximately 20-50 ms, 90-180 ms, and 300 ms, which were
      reproducible and graded in intensity and latency with distension pressure. From
      this basic study it is clear that colorectal evoked potentials can be recorded
      reliably in awake rats and may serve as an objective marker for centrally
      projecting visceral sensory signals in rodents. It remains to be seen how these
      responses are affected by drugs under development for clinical management of
      visceral pain, and if there is improved translation.

PMID- 22967009
TI  - Trends in the treatment of adults with ureteropelvic junction obstruction.
AB  - BACKGROUND AND PURPOSE: Minimally invasive pyeloplasty is an effective treatment
      for patients with ureteropelvic junction obstruction that offers quicker
      convalescence than open pyeloplasty. Technical challenges, however, may have
      limited its dissemination. We examined population trends and determinants of
      surgical options for ureteropelvic junction obstruction. PATIENTS AND METHODS:
      Using the State Inpatient and Ambulatory Surgery Databases for Florida, we
      identified adults who underwent ureteropelvic junction obstruction repair between
      2001 and 2009. After determining the surgical approach (minimally invasive
      pyeloplasty, open pyeloplasty, or endopyelotomy), we estimated annual utilization
      rates and the effects of patient, surgeon, and hospital predictors on surgery
      type, using multilevel multinomial logistic regression. RESULTS: Rates of
      minimally invasive pyeloplasty increased 360% (P for monotonic trend < 0.01),
      while rates of open pyeloplasty decreased 56% (P<0.01). Rates of endopyelotomy
      were substantially higher and remained relatively stable (P=0.27). Compared with
      open pyeloplasty, minimally invasive pyeloplasty was used more commonly among
      patients with private insurance (odds ratio [OR] 1.6; 95% confidence interval
      [CI], 1.2-2.3), those treated at teaching hospitals (OR 1.6; CI 1.0-2.6), and
      those treated by high-volume surgeons (OR 2.9; CI 2.0-4.2). Its use was less
      frequent among patients with multiple comorbidities (OR 0.53; CI 0.37-0.76).
      Similar associations were observed when comparing receipt of minimally invasive
      pyeloplasty with endopyelotomy; however, patients who underwent endopyelotomy
      were older. CONCLUSIONS: The use of minimally invasive pyeloplasty has
      dramatically increased, largely replacing open pyeloplasty, while the use of
      endopyelotomy, albeit significantly more common than the other approaches, has
      remained stable. The surgical approach is influenced by several patient, surgeon,
      and hospital factors.

PMID- 22967010
TI  - How aluminum adjuvants could promote and enhance non-target IgE synthesis in a
      genetically-vulnerable sub-population.
AB  - Aluminum-containing adjuvants increase the effectiveness of vaccination, but
      their ability to augment immune responsiveness also carries the risk of eliciting
      non-target responses, especially in genetically susceptible individuals. This
      study reviews the relevant actions of aluminum adjuvants and sources of genetic
      risk that can combine to adversely affect a vulnerable sub-population. Aluminum
      adjuvants promote oxidative stress and increase inflammasome activity, leading to
      the release of IL-1beta, IL-18, and IL-33, but not the important regulatory
      cytokine IL-12. In addition, they stimulate macrophages to produce PGE2, which
      also has a role in regulating immune responses. This aluminum-induced cytokine
      context leads to a T(H)2 immune response, characterized by the further release of
      IL-3, IL-4, IL-5, IL-9, IL-13, and IgE-potentiating factors such as sCD23.
      Genetic variants in cytokine genes, such as IL-4, IL-13, IL-33, and IL-18
      influence the response to vaccines in children and are also associated with
      atopy. These genetic factors may therefore define a genetically-vulnerable sub
      population, children with a family history of atopy, who may experience an
      exaggerated T(H)2 immune response to aluminum-containing vaccines. IL-4, sCD23,
      and IgE are common factors for both atopy and the immune-stimulating properties
      of aluminum adjuvants. IL-4 is critical in the production of IgE and total IgE up
      regulation. IL-4 has also been reported to induce the production of sCD23 and
      trigger resting sIgM+, sIgD+ B-cells to switch to sIgE+ B-cells, making them
      targets for IgE-potentiating factors. Further, the actions of IgE-potentiating
      factors on sIgE+ B-cells are polyclonal and unrestricted, triggering their
      differentiation into IgE-forming plasma cells. These actions provide a mechanism
      for aluminum-adjuvant promotion and enhancement of non-target IgE in a
      genetically vulnerable sub-population. Identification of these individuals may
      decrease the risk of adverse events associated with the use of aluminum
      containing vaccines.

PMID- 22967012
TI  - Reduced graphene oxide for catalytic oxidation of aqueous organic pollutants.
AB  - We discovered that chemically reduced graphene oxide, with an I(D)/I(G) >1.4
      (defective to graphite) can effectively activate peroxymonosulfate (PMS) to
      produce active sulfate radicals. The produced sulfate radicals (SO(4)(*-)) are
      powerful oxidizing species with a high oxidative potential (2.5-3.1 vs 2.7 V of
      hydroxyl radicals), and can effectively decompose various aqueous contaminants.
      Graphene demonstrated a higher activity than several carbon allotropes, such as
      activated carbon (AC), graphite powder (GP), graphene oxide (GO), and multiwall
      carbon nanotube (MWCNT). Kinetic study of graphene catalyzed activation of PMS
      was carried out. It was shown that graphene catalysis is superior to that on
      transition metal oxide (Co(3)O(4)) in degradation of phenol, 2,4-dichlorophenol
      (DCP) and a dye (methylene blue, MB) in water, therefore providing a novel
      strategy for environmental remediation.

PMID- 22967011
TI  - AbsIDconvert: an absolute approach for converting genetic identifiers at
      different granularities.
AB  - BACKGROUND: High-throughput molecular biology techniques yield vast amounts of
      data, often by detecting small portions of ribonucleotides corresponding to
      specific identifiers. Existing bioinformatic methodologies categorize and compare
      these elements using inferred descriptive annotation given this sequence
      information irrespective of the fact that it may not be representative of the
      identifier as a whole. RESULTS: All annotations, no matter the granularity, can
      be aligned to genomic sequences and therefore annotated by genomic intervals. We
      have developed AbsIDconvert, a methodology for converting between genomic
      identifiers by first mapping them onto a common universal coordinate system using
      an interval tree which is subsequently queried for overlapping identifiers.
      AbsIDconvert has many potential uses, including gene identifier conversion,
      identification of features within a genomic region, and cross-species
      comparisons. The utility is demonstrated in three case studies: 1) comparative
      genomic study mapping plasmodium gene sequences to corresponding human and
      mosquito transcriptional regions; 2) cross-species study of Incyte clone
      sequences; and 3) analysis of human Ensembl transcripts mapped by Affymetrix(r);
      and Agilent microarray probes. AbsIDconvert currently supports ID conversion of
      53 species for a given list of input identifiers, genomic sequence, or genome
      intervals. CONCLUSION: AbsIDconvert provides an efficient and reliable mechanism
      for conversion between identifier domains of interest. The flexibility of this
      tool allows for custom definition identifier domains contingent upon the
      availability and determination of a genomic mapping interval. As the genomes and
      the sequences for genetic elements are further refined, this tool will become
      increasingly useful and accurate. AbsIDconvert is freely available as a web
      application or downloadable as a virtual machine at:
      http://bioinformatics.louisville.edu/abid/.

PMID- 22967013
TI  - 24-hour urine collection in the metabolic evaluation of stone formers: is one
      study adequate?
AB  - Abstract Purpose: To determine whether one vs two 24-hour urine collections is
      optimal in the metabolic evaluation of nephrolithiasis. METHODS: We
      retrospectively reviewed all 24-hour urine collections performed at our tertiary
      stone clinic from July 1997 to February 2012. We identified patients with two 24
      hour urine collections performed <=10 days apart. Samples were analyzed by an
      outside laboratory for the standard urinary parameters. For each parameter,
      pairwise t tests were performed and Pearson correlation coefficients were
      calculated to compare samples 1 and 2. In addition, the number of cases that
      changed from normal to abnormal or vice versa was also evaluated for each
      parameter and the Kappa statistic was calculated. RESULTS: A total of 813
      subjects submitted two 24-hour urine collections <=10 days apart. Mean age was
      53.2 years, and mean body mass index was 28.8 kg/m(2). Based on creatinine 24/kg,
      subset analysis was performed for all properly collected samples (n=236). Using
      pairwise t test, 24-hour urine volume (P=0.0365) and phosphorus (P=0.0387) showed
      a statistically significant difference between samples 1 and 2. None of the other
      urinary parameters demonstrated a statistically significant difference when means
      were compared (pairwise t test, P>0.05), (range 0.061-0.9983). Pearson
      correlation demonstrated a high degree of correlation between two 24-hour urines
      for all variables (r=0.66-0.95, each P<0.0001). Depending on the urinary
      parameter assessed, 5.5% to 44.9% of patients changed from normalcy to
      abnormality, or vice versa. CONCLUSIONS: A single 24-hour urine collection may
      have changed clinical decision making in up to 45% of patients. Therefore, we
      recommend two collections to optimize the diagnostic yield and appropriately
      target stone prevention strategies.

PMID- 22967014
TI  - Uranyl adsorption at the muscovite (mica)/water interface studied by second
      harmonic generation.
AB  - Uranyl adsorption at the muscovite (mica)/water interface was studied by second
      harmonic generation (SHG). Using the nonresonant chi(3) technique and the Gouy
      Chapman model, the initial surface charge density of the mica surface was
      determined to be -0.022(1) C/m(2) at pH 6 and in the presence of dissolved
      carbonate. Under these same conditions, uranyl adsorption isotherms collected
      using nonresonant chi(3) experiments and resonantly enhanced SHG experiments that
      probe the ligand-to-metal charge transfer bands of the uranyl cation yielded a
      uranyl binding constant of 3(1) * 10(7) M(-1), corresponding to a Gibbs free
      energy of adsorption of -52.6(8) kJ/mol, and a maximum surface charge density at
      monolayer uranyl coverage of 0.028(3) C/m(2). These results suggest favorable
      adsorption of uranyl ions to the mica interface through strong ion-dipole or
      hydrogen interactions, with a 1:1 uranyl ion to surface site ratio that is
      indicative of monovalent cations ((UO(2))(3)(OH)(5)(+), (UO(2))(4)(OH)(7)(+),
      UO(2)OH(+), UO(2)Cl(+), UO(2)(CH(3)COO(-))(+)) binding at the interface, in
      addition to neutral uranyl species (UO(2)(OH)(2) and UO(2)CO(3)). This work
      provides benchmark measurements to be used in the improvement of contaminant
      transport modeling.

PMID- 22967016
TI  - Five-year follow-up of survival and relapse in patients who received cryotherapy
      during high-dose chemotherapy for stem cell transplantation shows no safety
      concerns.
AB  - We have previously published a randomised controlled study of the efficacy of
      cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for
      stem cell transplantation. The present study is a 5-year follow-up safety study
      of survival in these patients. In the previously published study oral cryotherapy
      (cooling of the oral cavity) during high-dose chemotherapy significantly reduced
      mucositis grade and opiate use in the treated group. All patients were followed
      up for at least 5 years with regard to relapse and death rates. Baseline data,
      transplant complications and mucositis data were compared. Significantly more
      patients (25/39) who received oral cryotherapy were alive after 5 years compared
      to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only
      baseline difference was a lower proportion of patients in complete remission at
      transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up
      study gave no support for safety concerns with cryotherapy.

PMID- 22967015
TI  - Secondary structure of rhBMP-2 in a protective biopolymeric carrier material.
AB  - Efficient delivery of growth factors is one of the great challenges of tissue
      engineering. Polyelectrolyte multilayer films (PEM) made of biopolymers have
      recently emerged as an interesting carrier for delivering recombinant human bone
      morphogenetic protein 2 (rhBMP-2 noted here BMP-2) to cells in a matrix-bound
      manner. We recently showed that PEM made of poly(l-lysine) and hyaluronan
      (PLL/HA) can retain high and tunable quantities of BMP-2 and can deliver it to
      cells to induce their differentiation in osteoblasts. Here, we investigate
      quantitatively by Fourier transform infrared spectroscopy (FTIR) the secondary
      structure of BMP-2 in solution as well as trapped in a biopolymeric thin film. We
      reveal that the major structural elements of BMP-2 in solution are intramolecular
      beta-sheets and unordered structures as well as alpha-helices. Furthermore, we
      studied the secondary structure of rhBMP-2 trapped in hydrated films and in dry
      films since drying is an important step for future applications of these
      bioactive films onto orthopedic biomaterials. We demonstrate that the structural
      elements were preserved when BMP-2 was trapped in the biopolymeric film in
      hydrated conditions and, to a lesser extent, in dry state. Importantly, its
      bioactivity was maintained after drying of the film. Our results appear highly
      promising for future applications of these films as coatings of biomedical
      materials, to deliver bioactive proteins while preserving their bioactivity upon
      storage in dry state.

PMID- 22967018
TI  - Light-induced switching of surfaces at wetting transitions through
      photoisomerization of polymer monolayers.
AB  - We report on a method to generate surfaces whose wettability can be reversibly
      switched between a superhydrophobic and Wenzel state or a Wenzel and superwetting
      state just by a short UV or VIS irradiation. To achieve this, we generate a
      silicon surface with a nanoscale roughness ("black silicon") and attach a polymer
      monolayer to it. The polymer contains a fluorinated azobenzene moiety which can
      be switched between the cis and trans state depending on the wavelength of the
      light used during illumination. The surface energy of the polymer coating is
      carefully adjusted to the energy value which separates distinct wetting regimes
      of the nanorough surface. This coupling of light induced switching to a
      transition of the wetting regimes can cause changes in the water contact angle as
      high as Deltatheta = 140 degrees  in the advancing CA or more than 175 degrees 
      in the receding CA even when the surface energy is changed only in a rather small
      range. Short irradiation times with UV or VIS light are enough to change the roll
      off angle from <5 degrees  to no roll off at all and back. We discuss the
      requirements necessary so that large changes in the contact angle occur during
      photoswitching processes on rough surfaces.

PMID- 22967017
TI  - Low or undetectable TPO receptor expression in malignant tissue and cell lines
      derived from breast, lung, and ovarian tumors.
AB  - BACKGROUND: Numerous efficacious chemotherapy regimens may cause
      thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag,
      represent a novel approach for the treatment of chemotherapy-induced
      thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte
      precursors, although little is known about its expression on other tissues.
      METHODS: Breast, lung, and ovarian tumor samples were analyzed for MPL expression
      by microarray and/or quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR), and for TPO-R protein expression by immunohistochemistry (IHC). Cell
      line proliferation assays were used to analyze the in vitro effect of eltrombopag
      on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell
      lines were also analyzed for TPO-R protein expression by Western blot. RESULTS:
      MPL mRNA was not detectable in 118 breast tumors and was detectable at only very
      low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR,
      low but detectable levels of MPL mRNA were detectable in some normal (14-43%) and
      malignant (3-17%) breast, lung, and ovarian tissues. A comparison of MPL to EPOR,
      ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those
      of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R
      protein expression in tumor tissues, confirming mRNA analysis. Culture of breast,
      lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a
      decrease in proliferation following incubation with eltrombopag. Western blot
      analyses revealed no detectable TPO-R protein expression in the lung carcinoma
      cell lines. CONCLUSIONS: Multiple analyses of breast, lung, and ovarian tumor
      samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein
      expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian
      tumor cell lines at doses likely to exert their actions on megakaryocytes and
      megakaryocyte precursors.

PMID- 22967019
TI  - Social work in the Veterans Administration hospital system: impact of the work.
AB  - Social workers in the Veterans Administration (VA) hospital system are faced with
      numerous challenges to best address the ongoing health and mental health needs of
      those who serve in the military. Social workers in the VA system serve diverse
      roles on the multidisciplinary medical teams and mental health services and are
      integral to the VA hospital environment. Most social workers feel positive about
      their work and their contributions to the care of the military. Despite positive
      feelings about their work, social workers are also prone to compassion fatigue
      and burnout as the work, especially with returning veterans from
      Afghanistan/Iraq, often extracts a toll. This article details the experience of
      social workers in the VA hospital system; it describes the impact of the work on
      the social workers, noting levels of compassion satisfaction, compassion fatigue,
      and burnout.

PMID- 22967020
TI  - Health education for social workers: a primer.
AB  - Health education, as a discipline and specialization, is often overshadowed by
      other branches of public health (e.g., bio-statistics, epidemiology, and policy
      management). Although social workers have been performing health education for
      decades, social work students may not know the history of health education as a
      practice profession and its uses in a social work context. The purpose of this
      article is to introduce the field of health education to social work students who
      are currently, or anticipate, practicing health education in their careers. We
      conclude with implications for social work education and a discussion about the
      impact of collaborative social work and health education efforts in the reduction
      of health disparities.

PMID- 22967021
TI  - An exploration of women's psychosocial support needs in the context of assisted
      reproduction.
AB  - This article explores the nature of psychosocial support needs and service
      provision in the context of assisted reproduction. Using qualitative data from a
      doctoral research project, the views of non-metropolitan women in Australia are
      presented along with a review of literature and an overview of participants'
      actual sources of, and needs in relation to, formal and informal support. It is
      argued that while social workers and other human service professionals have
      played a consistent role in providing psychosocial support to service users, the
      overarching approach to service provision remains biomedical in focus. This often
      adversely affects the overall quality of service provision. On this basis, social
      workers are urged to maintain their focus on human rights, respect, and
      multidimensional approaches to supporting women and their partners before,
      during, and after reproductive technology service use.

PMID- 22967022
TI  - A toolkit for single-session groups in acute care settings.
AB  - Single-session groups are an effective method for providing mutual aid to
      patients and families experiencing crisis in acute care/emergency settings. This
      toolkit provides health care professionals with practical guidance in
      establishing, recruiting for, and facilitating single-session groups in hospital
      settings. A two-step literature search was conducted to identify all relevant
      articles. The literature was retrieved and reviewed for inclusion. The results of
      this review form the basis of the toolkit. A framework for establishing this type
      of group is explored. Challenges and strategies concerning recruitment are
      discussed. The practice skills relevant to facilitating time-limited groups are
      outlined.

PMID- 22967023
TI  - Experiences of caregiving, satisfaction of life, and social repercussions among
      family caregivers, two years post-stroke.
AB  - Cerebrovascular diseases are a public health and social policy priority in Europe
      due to their high prevalence and the long-term disability they may result in (as
      the principal cause of handicap). Increasingly, family caregivers take over the
      care at home of these patients. Two years post-stroke, our study analyzed the
      feelings of family caregivers from Luxembourg and northeastern Portugal toward
      their experience of caregiving and its repercussions on social and couple
      relationships, life satisfaction, and socioeconomic characteristics.
      Participating hospitals identified survivors and consent was sought by letter.
      Patients (n = 62) and their main caregivers (n = 46 pairs) were interviewed at
      home. The mean life satisfaction of caregivers was similar, but the experience of
      providing care differed in terms of family support, and disruptions of the
      caregivers' family responsibilities. More Portuguese respondents gave activities
      up, found little time for relaxation, and estimated that their health had
      deteriorated; more Luxembourgers felt strong enough to cope. More Portuguese
      spouses reported an impact on their sex lives. Family caregivers represent a
      "population at risk." Social workers can help them by providing domestic
      assistance, undertaking coaching activities, fostering favorable attitudes, and
      offering reassurance. Home-based rehabilitation in Europe involving family care
      must take account of cultural lifestyle issues.

PMID- 22967024
TI  - Symptoms catastrophizing versus social hypervigilance in irritable bowel syndrome
      patients.
AB  - Western studies have revealed that symptoms catastrophizing (SC), a self-focused
      illness coping pattern, mediates poorer health outcomes in irritable bowel
      syndrome (IBS) patients. In light of the collective orientation of Chinese
      culture, an others-focused illness coping pattern named "symptoms-related social
      hypervigilance" (SSH) was constructed and explored together with SC in the
      current study. A cross-sectional questionnaire survey with 309 IBS patients
      recruited by 100% consecutive sampling was conducted. Exploratory factor analysis
      on the SSH scale provided a 9-item 3-factor solution. The three factors were 1)
      Anticipating negative perceptions from others; 2) Hiding symptoms in social
      situations; and 3) Assuming responsibility for total symptoms control. SC showed
      partial mediator properties between IBS symptoms severity and lowered health
      related quality of life. Whereas SSH did not show similar mediating effects, it
      was associated with 'proactive' illness behaviors which, if excessive, can lead
      to relentless pursuit of total symptoms elimination.

PMID- 22967027
TI  - Acute diverticulitis: demographic, clinical and laboratory features associated
      with computed tomography findings in 741 patients.
AB  - BACKGROUND: Computed tomography (CT) demonstrates diverticulitis severity. AIM:
      To assess demographic, clinical and leucocyte features in association with
      severity. METHODS: We reviewed medical records of 741 emergency department cases
      and in-patients with diverticulitis. CT findings were: (i) nondiagnostic; (ii)
      moderate (peri-colic inflammation); and (iii) severe (abscess and/or extra
      luminal gas and/or contrast). RESULTS: Patients with severe vs.
      nondiagnostic/moderate findings had fewer females (42.4% vs. 58.2%, P = .004),
      less lower abdominal pain only (74.7% vs. 83.7%, P = .042) and more constipation
      (24.4% vs. 12.5%, P = .002), fever (52.2% vs. 27.0%, P < .0001), leucocytosis
      (81.5% vs. 55.2%, P < .0001), neutrophilia (86.2% vs. 59.0%, P < .0001),
      'bandemia' (18.5% vs. 5.5%, P < .0001) and the triad of abdominal pain, fever and
      leucocytosis (46.7% vs. 19.9%, P < .0001) respectively. Severe vs.
      nondiagnostic/moderate findings occurred in 4.8% vs. 95.2% without fever or
      leucocytosis, 7.0% vs. 93.0% with fever, 12.3% vs. 87.7% with leucocytosis and
      25.1% vs. 74.9% with fever and leucocytosis respectively (P < .0001). The former
      group (odds ratio [95% CI]) included females less often (0.45 [0.26-0.76]) and
      had less lower abdominal pain only (0.54 [0.29-0.99]) and more constipation (2.32
      [1.27-4.23]), fever (2.13 [1.27-3.57]) and leucocytosis (2.67 [1.43-4.99]).
      CONCLUSIONS: Less than 50% of severe cases have the clinical/laboratory triad of
      abdominal pain, fever and leucocytosis, but only 1 of 20 with pain who lack fever
      and leucocytosis have severe diverticulitis. Male gender, pain not limited to the
      lower abdomen, constipation, fever and leucocytosis are independently associated
      with severe diverticulitis.

PMID- 22967026
TI  - Probing secondary glutaminyl cyclase (QC) inhibitor interactions applying an in
      silico-modeling/site-directed mutagenesis approach: implications for drug
      development.
AB  - Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate-modified
      amyloid peptides deposited in neurodegenerative disorders such as Alzheimer's
      disease. Inhibitors of QC are currently in development as potential therapeutics.
      The crystal structures of the potent inhibitor PBD150 bound to human and murine
      QC (hQC, mQC) have been described recently. The binding modes of a
      dimethoxyphenyl moiety of the inhibitor are significantly different between the
      structures, which contrasts with a similar K(i)  value. We show the conformation
      of PBD150 prone to disturbance by protein-protein interactions within the
      crystals. Semi-empirical calculations of the enzyme-inhibitor interaction within
      the crystal suggest significant differences in the dissociation constants between
      the binding modes. To probe for interactions in solution, a site-directed
      mutagenesis on hQC was performed. The replacement of F325 and I303 by alanine or
      asparagine resulted in a 800-fold lower activity of the inhibitor, whereas the
      exchange of S323 by alanine or valine led to a 20-fold higher activity of PBD150.
      The results provide an example of deciphering the interaction mode between a
      target enzyme and lead substance in solution, if co-crystallization does not
      mirror such interactions properly. Thus, the study might provide implications for
      rapid screening of binding modes also for other drug targets.

PMID- 22967028
TI  - N-Heterocyclic carbene-catalyzed annulation of alpha-cyano-1,4-diketones with
      ynals.
AB  - In this paper, the first stereoselective annulation reaction between alpha-cyano
      1,4-diketones and ynals, mediated by catalytic amounts of a triazolium salt
      precatalyst and cocatalytic amounts of a weak carboxylate base, is disclosed. The
      title transformation proceeds smoothly under mild reaction conditions and
      generates three contiguous stereogenic centers, one of which is a quaternary
      acetal carbon. This reaction tolerates a wide variety of electronically distinct
      substituents on both reaction partners and affords privileged bicyclic scaffolds
      in 61-90% isolated yields and with up to 20:1 diastereomeric preference.

PMID- 22967029
TI  - Diabetes related knowledge among residents and nurses: a multicenter study in
      Karachi, Pakistan.
AB  - BACKGROUND: Assessment of knowledge among resident trainees and nurses is very
      important since majority of patients admitted in hospital have underlying
      diabetes which could lead to adverse clinical outcomes if not managed
      efficiently. Therefore, the purpose of this study was to evaluate and compare the
      knowledge related to the management of diabetes among registered nurses (RN) and
      trainee residents of internal medicine (IMR), family medicine (FMR) and surgery
      (SR) at tertiary care hospitals of Karachi, Pakistan. METHODS: A validated
      questionnaire consisting of 21 open ended questions related to diabetes awareness
      was acquired through a study done at Thomas Jefferson University Hospital,
      Philadelphia with the permission of primary author. RESULTS: 169 IMR, 27 FMR, 86
      SR and 99 RN completed a questionnaire that assessed the knowledge related to
      different aspects of management of diabetes. The results were further stratified
      by participant's specialty and level of training. The percentage of knowledge
      based questions answered correctly was found to be low. The overall mean correct
      percentage among all the participants was 50% +/- 21. There was no statistical
      difference in terms of knowledge between IMR & FMR residents (64% +/- 14 vs. 60%
      +/- 16, p = 0.47) respectively. The total scores of SR and RN were quite low (40%
      +/- 16 & 31% +/- 15 respectively).SR and RN were found to have profound deficit
      in both inpatient and outpatient knowledge of diabetes. We did not observe any
      improvement in level of knowledge of FMR & SR with increase in duration of their
      training (p = 0.47 & 0.80 respectively). In contrast, improvement in the level of
      knowledge of IMR was observed from first to second year of their training (p =
      0.03) with no further improvement thereafter. RN's didn't respond correctly on
      most of the items related to in-patient management of diabetes (Mean score 40% +/
      20). CONCLUSION: As there are no prior studies in our setting evaluating
      knowledge related to diabetes management among residents and nurses, this study
      is of paramount importance. Based on these results, considerable knowledge gaps
      were found among trainee residents and nurses pointing towards need of providing
      additional education to improve the delivery of diabetes care.

PMID- 22967031
TI  - Overexpression of hydroperoxide lyase, peroxygenase and epoxide hydrolase in
      tobacco for the biotechnological production of flavours and polymer precursors.
AB  - Plants produce short-chain aldehydes and hydroxy fatty acids, which are important
      industrial materials, through the lipoxygenase pathway. Based on the information
      that lipoxygenase activity is up-regulated in tobacco leaves upon infection with
      tobacco mosaic virus (TMV), we introduced a melon hydroperoxide lyase (CmHPL)
      gene, a tomato peroxygenase (SlPXG) gene and a potato epoxide hydrolase (StEH)
      into tobacco leaves using a TMV-based viral vector system to afford aldehyde and
      hydroxy fatty acid production. Ten days after infiltration, tobacco leaves
      infiltrated with CmHPL displayed high enzyme activities of 9-LOX and 9-HPL, which
      could efficiently transform linoleic acid into C(9) aldehydes. Protein extracts
      prepared from 1 g of CmHPL-infiltrated tobacco leaves (fresh weight) in
      combination with protein extracts prepared from 1 g of control vector-infiltrated
      tobacco leaves (as an additional 9-LOX source) produced 758 +/- 75 MUg total C(9)
      aldehydes in 30 min. The yield of C(9) aldehydes from linoleic acid was 60%.
      Besides, leaves infiltrated with SlPXG and StEH showed considerable enzyme
      activities of 9-LOX/PXG and 9-LOX/EH, respectively, enabling the production of
      9,12,13-trihydroxy-10(E)-octadecenoic acid from linoleic acid. Protein extracts
      prepared from 1 g of SlPXG-infiltrated tobacco leaves (fresh weight) in
      combination with protein extracts prepared from 1 g of StEH-infiltrated tobacco
      leaves produced 1738 +/- 27 MUg total 9,12,13-trihydroxy-10(E)-octadecenoic acid
      isomers in 30 min. The yield of trihydroxyoctadecenoic acids from linoleic acid
      was 58%. C(9) aldehydes and trihydroxy fatty acids could likely be produced on a
      larger scale using this expression system with many advantages including easy
      handling, time-saving and low production cost.

PMID- 22967032
TI  - Laboratory quality assurance in the Department of Restorative Dentistry at the
      University of Illinois at Chicago, College of Dentistry.
AB  - PURPOSE: The purpose of this study was to evaluate data collected in University
      of Illinois at Chicago College of Dentistry (UIC COD) laboratory quality
      assurance (QA) forms, analyze the collected data, and create a report of the
      findings. The goals of the study were to (1) identify the most common mistakes
      occurring during laboratory and clinical procedures when performing prosthodontic
      treatment, (2) note the incidence and trends of mistakes made by D3, D4, and
      IDDP2 students, and (3) observe any differences in the types of mistakes made by
      D3, D4, and IDDP2. MATERIALS AND METHODS: QA data from June 1, 2007 to May 31,
      2009 were evaluated based on forms gathered from the QA dental laboratory from
      all D3, D4, and IDDP2 students' submissions. All students had graduated from the
      UIC COD at the time of collection. Data were recorded for type of errors made in
      submission of laboratory work (Indirect Restorations [IR], Removable Partial
      Dentures [RPD], Complete Dentures [CD]), year of student in dental school (D3,
      D4, IDDP2), and frequency of rejection for each respective student. The frequency
      of common mistakes were pooled, evaluated, and reported by respective class year.
      RESULTS: The five most common laboratory submission errors for D3, D4, and IDDP2
      students were nearly the same among student years for IR, RPD, and CD. D4
      students had disproportionately higher numbers of work rejections compared to D3
      and IDDP2 students. CONCLUSIONS: D4 students had a higher percentage of
      laboratory submission errors compared to D3 students for all laboratory
      procedures. There were similar types of errors noted between foreign-trained
      students (IDDP2) and domestically trained students (D3, D4).

PMID- 22967030
TI  - Late morfofunctional alterations of the Sertoli cell caused by doxorubicin
      administered to prepubertal rats.
AB  - BACKGROUND: Doxorubicin is a potent chemotherapeutic drug used against a variety
      of cancers. It acts through interaction with polymerases and topoisomerase II and
      free radical production. Doxorubicin activity is not specific to cancer cells and
      can also damage healthy cells, especially those undergoing rapid proliferation,
      such as spermatogonia. In previous studies our group showed that etoposide,
      another topoisomarese II poison, causes irreversible damage to Sertoli cells.
      Thus, the aim of this study was to address the effects of doxorubicin on Sertoli
      cell morphology and function and on the seminiferous epithelium cycle when
      administered to prepubertal rats. METHODS: Prepubertal rats received the dose of
      5 mg/Kg of doxorubicin, which was fractioned in two doses: 3 mg/Kg at 15dpp and 2
      mg/Kg at 22 dpp. The testes were collected at 40, 64 and 127 dpp, fixed in
      Bouin's liquid and submitted to transferrin immunolabeling for Sertoli cell
      function analysis. Sertoli cell morphology and the frequency of the stages of the
      seminiferous epithelium cycle were analyzed in PAS + H-stained sections. RESULTS:
      The rats treated with doxorubicin showed reduction of transferrin labeling in the
      seminiferous epithelium at 40 and 64 dpp, suggesting that Sertoli cell function
      is altered in these rats. All doxorubicin-treated rats showed sloughing and
      morphological alterations of Sertoli cells. The frequency of the stages of the
      seminiferous epithelium cycle was also affected in all doxorubicin-treated rats.
      CONCLUSIONS AND DISCUSSION: These data show that doxorubicin administration
      during prepuberty causes functional and morphological late damage to Sertoli
      cells; such damage is secondary to the germ cell primary injury and contributed
      to enhance the spermatogenic harm caused by this drug. However, additional
      studies are required to clarify if there is also a direct effect of doxorubicin
      on Sertoli cells producing a primary damage on these cells.

PMID- 22967033
TI  - Photoperiod-dependent regulation of carboxypeptidase E affects the selective
      processing of neuropeptides in the seasonal Siberian hamster (Phodopus sungorus).
AB  - The production of bioactive peptides from biologically inactive precursors
      involves extensive post-translational processing, including enzymatic cleavage by
      proteolytic peptidases. Endoproteolytic prohormone-convertases initially cleave
      the precursors of many neuropeptides at specific amino acid sequences to generate
      intermediates with basic amino acid extensions on their C-termini. Subsequently,
      the related exopeptidases, carboxypeptidases D and E (CPD and CPE), are
      responsible for removing these amino acids before the peptides achieve biological
      activity. We investigated the effect of photoperiod on the processing of the
      neuropeptide precursor pro-opiomelanocortin (POMC) and its derived neuropeptides,
      alpha-melanocyte-stimulating hormone (MSH) and beta-endorphin (END), within the
      hypothalamus of the seasonal Siberian hamster (Phodopus sungorus). We thus
      compared hypothalamic distribution of CPD, CPE, alpha-MSH and beta-END using
      immunohistochemistry and measured the enzyme activity of CPE and concentrations
      of C-terminally cleaved alpha-MSH in short-day (SD; 8 : 16 h light/dark) and long
      day (LD; 16 : 8 h light/dark) acclimatised hamsters. Increased immunoreactivity (
      IR) of CPE, as well as higher CPE activity, was observed in SD. This increase was
      accompanied by more beta-END-IR cells and substantially higher levels of C-
      terminally cleaved alpha-MSH, as determined by radioimmunoassay. Our results
      suggest that exoproteolytic cleavage of POMC-derived neuropeptides is tightly
      regulated by photoperiod in the Siberian hamster. Higher levels of biological
      active alpha-MSH- and beta-END in SD are consistent with the hypothesis that post
      translational processing is a key event in the regulation of seasonal energy
      balance.

PMID- 22967034
TI  - Psychological trajectories in the year after a newly diagnosed seizure.
AB  - PURPOSE: Underdiagnosed depression and anxiety are well-recognized issues in
      chronic epilepsy, but the evolution of these symptoms after diagnosis is not well
      understood. We aimed to identify mood trajectories after a first seizure, and to
      examine factors impacting these trajectories. METHODS: Seventy-four patients were
      evaluated at 1, 3, and 12 months with (1) the Hospital Anxiety and Depression
      Scale, and (2) a semistructured interview assessing patients' initial
      psychological reaction to the seizure at 1 month (limited vs. pervasive loss of
      control). The SAS Institute's TRAJ data modelling procedure was employed to
      delineate trajectories. KEY FINDINGS: Two depression and three anxiety
      trajectories were identified, with significant overlap. The majority of patients
      (~ 74%) followed a trajectory with low depression throughout the study, and
      either low or moderate anxiety. A minority followed trajectories with high
      depression and anxiety from diagnosis (~ 16%). Patients with high levels of
      distress were adversely affected by seizure recurrence and antiepileptic drugs
      (AEDs), whereas those with low levels were not. Trajectories were predicted by
      the patient's sense of loss of control early after diagnosis and were weakly
      related to demographic and medical variables (age, gender, education,
      relationship status, psychiatric history, and prior epileptic events).
      SIGNIFICANCE: Methods that account for heterogeneity in patient responses are
      critical for developing a clinically relevant understanding of adjustment after a
      newly diagnosed seizure. Most patients appear to be resilient in the face of
      early seizures, whereas those at risk of longer-term psychological difficulties
      may be evident from diagnosis. Early screening for depression and anxiety is
      warranted.

PMID- 22967035
TI  - Long-term efficacy and safety of safinamide as add-on therapy in early
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Safinamide is an alpha-aminoamide with both dopaminergic
      and non-dopaminergic mechanisms of action in Phase III clinical development as a
      once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease
      (PD). METHODS: Study 017 was a 12-month, randomized, double-blind, placebo
      controlled pre-planned extension study to the previously reported Study 015.
      Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in
      early PD. The primary efficacy endpoint was the time from baseline (Study 015
      randomization) to 'intervention', defined as increase in DA dose; addition of
      another DA, levodopa or other PD treatment; or discontinuation due to lack of
      efficacy. Safinamide groups were pooled for the primary efficacy endpoint
      analysis; post hoc analyses were performed on each separate dose group. RESULTS:
      Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and
      187/227 (82%) patients completed the extension study. Median time to intervention
      was 559 and 466 days in the pooled safinamide and placebo groups, respectively
      (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide
      100 mg/day experienced a significantly lower rate of intervention compared with
      placebo (25% vs. 51%, respectively) and a delay in median time to intervention of
      9 days (P < 0.05; 240- to 540-day analysis). CONCLUSIONS: The pooled data from
      the safinamide groups failed to reach statistical significance for the primary
      endpoint of median time from baseline to additional drug intervention. Post hoc
      analyses indicate that safinamide 100 mg/day may be effective as add-on treatment
      to DA in PD.

PMID- 22967036
TI  - A meta-analysis of randomized clinical trials that compared ultrasonic energy and
      monopolar electrosurgical energy in laparoscopic cholecystectomy.
AB  - BACKGROUND: Currently, monopolar electrical energy is still widely used as the
      main source of energy for laparoscopic cholecystectomy (LC). However, some
      studies have suggested that the use of ultrasonic energy is more advantageous.
      This meta-analysis pooled the currently published randomized controlled trials
      comparing the safety and efficacy of ultrasonic energy and monopolar electrical
      energy in LC. MATERIALS AND METHODS: MEDLINE, EMBASE, Science Citation Index
      Expanded, and the Cochrane Central Register of Controlled Trials for relevant
      articles published between January 1985 to February 2012 by using the search
      terms "laparoscopic cholecystectomy," "electrocoagulation," "electrosurgery,"
      "ultrasonics," "ultrasonic therapy," and "dissection." Intraoperative and
      postoperative measures and complications were evaluated. RESULTS: Eight high
      quality randomized controlled trials with 1056 patients were included.
      Differences in mean operation time, mean blood loss, mean hospital stay,
      gallbladder perforation, and postoperative abdominal pain score at 24 hours were
      statistically significant between the two groups, in favor of the use of
      ultrasonic energy. However, there were no differences in operation conversion,
      bile leakage, intra-abdominal collections, and postoperative nausea at 24 hours.
      CONCLUSIONS: Ultrasonic energy is as safe and effective as electrosurgical energy
      and potentially might be safer in LC. However, the financial implications of this
      technical modality need to be established in cost-effectiveness analysis.

PMID- 22967037
TI  - Extended pelvic lymph node dissection including internal iliac packet should be
      performed during robot-assisted laparoscopic radical prostatectomy for high-risk
      prostate cancer.
AB  - INTRODUCTION: The indication and anatomic limits of pelvic lymph node dissection
      (PLND) have not been clearly defined. Therefore, we assessed whether the extent
      of PLND at robot-assisted laparoscopic radical prostatectomy (RALP) had any
      benefit on lymph node yield, staging accuracy, and biochemical recurrence (BCR)
      in patients with high-risk prostate cancer. PATIENTS AND METHODS: Between July
      2005 and July 2010, a retrospective analysis was performed on 200 patients with
      high-risk prostate cancer stratified by D'Amico classification. The study
      population was divided into different groups: patients in Group 1 had standard
      PLND, and Group 2 had extended PLND (ePLND). The clinicopathologic findings of
      patients and surgical outcomes of PLND with each procedure were measured. Kaplan
      Meier and log rank tests were used to estimate BCR-free survival rates.
      Univariate and multivariate survival analyses were done with the Cox proportional
      hazard regression model. RESULTS: Medians of 15 (interquartile range, 11-19) and
      24 (interquartile range, 18-28) lymph nodes were dissected in Groups 1 and 2,
      respectively (P<.001). The incidences of lymph node metastasis were 5.2% (8/155)
      in Group 1 and 22.2% (10/45) in Group 2. Regardless of the extent of PLND, the
      patients with positive lymph nodes had a significantly lower BCR-free survival
      than those with negative lymph nodes. Twenty-five percent (7/27) of positive
      lymph nodes were in the internal iliac packet and common iliac packet. In
      particular, of the positive internal iliac nodes, 75% (3/4) of nodes were found
      in that location, exclusively. CONCLUSIONS: An ePLND that identifies patients
      with lymph node metastasis including the internal iliac packet during RALP
      provides an accurate pathologic staging and may have survival benefits in high
      risk prostate cancer.

PMID- 22967039
TI  - Impact of robotic technique and surgical volume on the cost of radical
      prostatectomy.
AB  - BACKGROUND AND PURPOSE: Our present understanding of the effect of robotic
      surgery and surgical volume on the cost of radical prostatectomy (RP) is limited.
      Given the increasing pressures placed on healthcare resource utilization, such
      determinations of healthcare value are becoming increasingly important.
      Therefore, we performed a study to define the effect of robotic technology and
      surgical volume on the cost of RP. METHODS: The state of Maryland mandates that
      all acute-care hospitals report encounter-level and hospital discharge data to
      the Health Service Cost Review Commission (HSCRC). The HSCRC was queried for men
      undergoing RP between 2008 and 2011 (the period during which robot-assisted
      laparoscopic radical prostatectomy [RALRP] was coded separately). High-volume
      hospitals were defined as >60 cases per year, and high-volume surgeons were
      defined as >40 cases per year. Multivariate regression analysis was performed to
      evaluate whether robotic technique and high surgical volume impacted the cost of
      RP. RESULTS: There were 1499 patients who underwent RALRP and 2565 who underwent
      radical retropubic prostatectomy (RRP) during the study period. The total cost
      for RALRP was higher than for RRP ($14,000 vs 10,100; P<0.001) based primarily on
      operating room charges and supply charges. Multivariate regression demonstrated
      that RALRP was associated with a significantly higher cost (beta coeff 4.1;
      P<0.001), even within high-volume hospitals (beta coeff 3.3; P<0.001). High
      volume surgeons and high-volume hospitals, however, were associated with a
      significantly lower cost for RP overall. High surgeon volume was associated with
      lower cost for RALRP and RRP, while high institutional volume was associated with
      lower cost for RALRP only. CONCLUSIONS: High surgical volume was associated with
      lower cost of RP. Even at high surgical volume, however, the cost of RALRP still
      exceeded that of RRP. As robotic surgery has come to dominate the healthcare
      marketplace, strategies to increase the role of high-volume providers may be
      needed to improve the cost-effectiveness of prostate cancer surgical therapy.

PMID- 22967038
TI  - After TGN1412: recent developments in cytokine release assays.
AB  - The failure of regulatory science to keep pace with and support the development
      of new biological medicines was very publically highlighted in March 2006 when
      the first-in-man Phase I clinical trial of the immunomodulatory CD28-specific
      monoclonal antibody (mAb) TGN1412 ended in disaster when all six volunteers
      suffered a life-threatening adverse reaction termed a 'Cytokine Storm'. The poor
      predictive value of standard pre-clinical safety tests and animal models applied
      to TGN1412 demonstrated the need for a new generation of immunotoxicity assays
      and animal models that are both sensitive and predictive of clinical outcome in
      man. The non-predictive result obtained from pre-clinical safety testing in
      cynomolgus macaques has now been attributed to a lack of CD28 expression on CD4+
      effector memory T-cells that therefore cannot be stimulated by TGN1412. In
      contrast, high levels of CD28 are expressed on human CD4+ effector memory T
      cells, the source of most TGN1412-stimulated pro-inflammatory cytokines. Standard
      in vitro safety tests with human cells were also non-predictive as they did not
      replicate in vivo presentation of TGN1412. It was subsequently shown that, if an
      immobilized therapeutic mAb-based assay or endothelial cell co-culture assay was
      used to evaluate TGN1412, then these would have predicted a pro-inflammatory
      response in man. New in vitro assays based on these approaches are now being
      applied to emerging therapeutics to hopefully prevent a repeat of the TGN1412
      incident. It has emerged that the mechanism of pro-inflammatory cytokine release
      stimulated by TGN1412 is different to that of other therapeutic mAbs, such that
      standard pro-inflammatory markers such as TNFalpha and IL-8 are not
      discriminatory. Rather, IL-2 release and lymphoproliferation are optimal readouts
      of a TGN1412-like pro-inflammatory response.

PMID- 22967040
TI  - Carvacrol decreases neuronal excitability by inhibition of voltage-gated sodium
      channels.
AB  - The monoterpenoid carvacrol (1) is present in many essential oils of plants and
      has attracted attention because of its beneficial biological activities,
      especially analgesic activity. However, the mechanism of action of 1 remains
      unknown. The present study aimed to explore the mechanisms whereby 1 produces its
      effects on the peripheral nervous system. Carvacrol reversibly blocked the
      excitability of the rat sciatic nerve in a concentration-dependent manner with an
      IC(50) value of 0.50 +/- 0.04 mM. At 0.6 mM, 1 increased the rheobase from 3.30
      +/- 0.06 V to 4.16 +/- 0.14 V and the chronaxy from 59.6 +/- 1.22 MUs to 75.0 +/-
      1.82 MUs. Also, 1 blocked the generation of action potentials (IC(50) 0.36 +/-
      0.14 mM) of the intact dorsal root ganglion (DRG) neurons without altering the
      resting potential and input resistance. Carvacrol reduced the voltage-gated
      sodium current of dissociated DRG neurons (IC(50) 0.37 +/- 0.05 mM). In this
      study it has been demonstrated that 1 blocks neuronal excitability by a direct
      inhibition of the voltage-gated sodium current, which suggests that this compound
      acts as a local anesthetic. The present findings add valuable information to help
      understand the mechanisms implicated in the analgesic activity of carvacrol.

PMID- 22967041
TI  - The impact of obesity on urine composition and nephrolithiasis management.
AB  - BACKGROUND AND PURPOSE: Several studies have reported that obese patients have a
      higher risk of nephrolithiasis. The purpose of this study is to investigate the
      effect of overweight (OW) and obesity on stone composition, type of treatment,
      and urine composition. METHODS: With Institutional Review Board approval, charts
      of adult patients who attended our dedicated stone clinic over a 5-year period
      starting January 2006 were reviewed. Patients were categorized into normal (body
      mass index 18.5-24.9), OW (25-29.9), and obese (>=30). We excluded those who did
      not have at least one 24-hour urine analysis. RESULTS: OW and obese patients were
      more likely to have previous stones, more chance to have uric acid stones, and to
      be treated with shockwave lithotripsy in the community, and with ureteroscopy or
      percutaneous nephrolithotripsy in our center. They needed more thiazide
      diuretics, allopurinol, and dietitian counseling. They had statistically
      significant (P<0.05) higher urine calcium, citrate, supersaturation calcium
      phosphate, uric acid, supersaturation uric acid, sodium, potassium, magnesium,
      phosphorus, chloride, sulfate, urine urea nitrogen, protein catabolic rate, and
      creatinine compared with those with normal weight. CONCLUSION: OW and obese
      patients have different stone composition with increased excretion of stone
      promoters in the urine. Stone prevention measures should be introduced during
      metabolic syndrome evaluation.

PMID- 22967042
TI  - Giant magnetoresistance and anomalous magnetic properties of highly epitaxial
      ferromagnetic LaBaCo2O(5.5+delta) thin films on (001) MgO.
AB  - Ferromagnetic thin films of the A-site nano-ordered double perovskite
      LaBaCo(2)O(5.5+delta) (LBCO) were grown on (001) MgO, and their structural and
      magnetic properties were characterized. The as-grown films have an excellent
      epitaxial behavior with atomically sharp interfaces, with the c-axis of the LBCO
      structure lying in the film plane and the interface relationship given by
      (100)(LBCO)//(001)(MgO) and [001](LBCO)//[100](MgO) or [010](MgO). The as-grown
      LBCO films exhibit a giant magnetoresistance (54% at 40 K under 7 T) and an
      anomalous magnetic hysteresis, depending strongly on the temperature and the
      applied magnetic field scan width.

PMID- 22967043
TI  - Controlled nuclear import of the transcription factor NTL6 reveals a cytoplasmic
      role of SnRK2.8 in the drought-stress response.
AB  - Controlled proteolytic activation of membrane-anchored transcription factors
      provides an adaptation strategy that guarantees rapid transcriptional responses
      to abrupt environmental stresses in both animals and plants. NTL6 is a plant
      specific NAC [NAM/ATAF1/2/CUC2] transcription factor that is expressed as a
      dormant plasma membrane-associated form in Arabidopsis. Proteolytic processing of
      NTL6 is triggered by abiotic stresses and ABA (abscisic acid). In the present
      study, we show that NTL6 is linked directly with SnRK (Snf1-related protein
      kinase) 2.8-mediated signalling in inducing a drought-resistance response.
      SnRK2.8 phosphorylates NTL6 primarily at Thr142. NTL6 phosphorylation by SnRK2.8
      is required for its nuclear import. Accordingly, a mutant NTL6 protein, in which
      Thr142 was mutated to an alanine, was poorly phosphorylated and failed to enter
      the nucleus. In accordance with the role of SnRK2.8 in drought-stress signalling,
      transgenic plants overproducing either NTL6 or its active form 6DeltaC (35S:NTL6
      and 35S:6DeltaC) exhibited enhanced resistance to water-deficit conditions such
      as those overproducing SnRK2.8 (35S:SnRK2.8). In contrast, NTL6 RNAi (RNA
      interference) plants were susceptible to dehydration as observed in the SnRK2.8
      deficient snrk2.8-1 mutant. Furthermore, the dehydration-resistant phenotype of
      35S:NTL6 transgenic plants was compromised in 35S:NTL6 X snrk2.8-1 plants. These
      observations indicate that SnRK2.8-mediated protein phosphorylation, in addition
      to a proteolytic processing event, is important for NTL6 function in inducing a
      drought-resistance response.

PMID- 22967044
TI  - Analysis of induction mechanisms of an insulin-inducible transcription factor
      SHARP-2 gene by (-)-epigallocatechin-3-gallate.
AB  - The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin
      inducible transcription factor. In this study, we examined the mechanism(s)
      involved in the regulation of the rat SHARP-2 gene expression by (-)
      epigallocatechin-3-gallate (EGCG). The induction of SHARP-2 mRNA by EGCG was
      repressed by pretreatments with inhibitors for either phosphoinositide 3-kinase
      (PI3K) or RNA polymerase II. Then, we examined a biological relationship between
      EGCG and transcription factor NF-kappaB interfering with the insulin action. The
      protein levels of the NF-kappaB were rapidly decreased by an EGCG treatment.
      Finally, the mechanism(s) of transcriptional activation of the rat SHARP-2 gene
      by both NF-kappaB and EGCG was analyzed. While overexpression of the NF-kappaB
      p65 protein decreased the promoter activity of the SHARP-2 gene, EGCG did not
      affect it. Thus, we conclude that EGCG induces the expression of the rat SHARP-2
      gene via both the PI3K pathway and degradation of the NF-kappaB p65 protein.

PMID- 22967045
TI  - The impact of workplace factors on evidence-based speech-language pathology
      practice for children with autism spectrum disorders.
AB  - Although researchers have examined barriers to implementing evidence-based
      practice (EBP) at the level of the individual, little is known about the effects
      workplaces have on speech-language pathologists' implementation of EBP. The aim
      of this study was to examine the impact of workplace factors on the use of EBP
      amongst speech-language pathologists who work with children with Autism Spectrum
      Disorder (ASD). This study sought to (a) explore views about EBP amongst speech
      language pathologists who work with children with ASD, (b) identify workplace
      factors which, in the participants' opinions, acted as barriers or enablers to
      their provision of evidence-based speech-language pathology services, and (c)
      examine whether or not speech-language pathologists' responses to workplace
      factors differed based on the type of workplace or their years of experience. A
      total of 105 speech-language pathologists from across Australia completed an
      anonymous online questionnaire. The results indicate that, although the majority
      of speech-language pathologists agreed that EBP is necessary, they experienced
      barriers to their implementation of EBP including workplace culture and support,
      lack of time, cost of EBP, and the availability and accessibility of EBP
      resources. The barriers reported by speech-language pathologists were similar,
      regardless of their workplace (private practice vs organization) and years of
      experience.

PMID- 22967047
TI  - Photochemical behavior of polylactide/ZnO nanocomposite films.
AB  - This study reports the effect of light on PLA/ZnO nanocomposites films produced
      by melt-extrusion. The attention focused on the discrimination between the
      photocatalytic degradation of PLA provoked by ZnO and the UV screening effect of
      the ZnO nanoparticles. The chemical modifications of PLA induced by UV light
      irradiation were analyzed using infrared spectroscopy and completed through the
      analysis of the low-molecular-weight photoproducts using IC and SPME and the
      characterization of chain scissions with SEC. A comprehensive mechanism for the
      photooxidation of PLA was then proposed. The results indicated that the
      photocatalytic activity of ZnO nanoparticles induces the oxidation of PLA.
      Because ZnO limits the penetration of light inside the samples, this effect
      mainly concerns the first micrometers at the surface of the exposed samples.
      Cross-sectional analysis using micro-IR and ATR-IR spectroscopies was performed
      to highlight the degradation profile in the PLA/ZnO nanocomposites.

PMID- 22967048
TI  - Comment on "direct observation of tetrahedrally coordinated Fe(III) in
      ferrihydrite".

PMID- 22967046
TI  - Limited, episodic diversification and contrasting phylogeography in a New Zealand
      cicada radiation.
AB  - BACKGROUND: The New Zealand (NZ) cicada fauna contains two co-distributed
      lineages that independently colonized the isolated continental fragment in the
      Miocene. One extensively studied lineage includes 90% of the extant species
      (Kikihia + Maoricicada + Rhodopsalta; ca 51 spp.), while the other contains just
      four extant species (Amphipsalta - 3 spp. + Notopsalta - 1 sp.) and has been
      little studied. We examined mitochondrial and nuclear-gene phylogenies and
      phylogeography, Bayesian relaxed-clock divergence timing (incorporating
      literature-based uncertainty of molecular clock estimates) and ecological niche
      models of the species from the smaller radiation. RESULTS: Mitochondrial and
      nuclear-gene trees supported the monophyly of Amphipsalta. Most interspecific
      diversification within Amphipsalta-Notopsalta occurred from the mid-Miocene to
      the Pliocene. However, interspecific divergence time estimates had large
      confidence intervals and were highly dependent on the assumed tree prior, and
      comparisons of uncorrected and patristic distances suggested difficulty in
      estimation of branch lengths. In contrast, intraspecific divergence times varied
      little across analyses, and all appear to have occurred during the Pleistocene.
      Two large-bodied forest taxa (A. cingulata, A. zelandica) showed minimal
      phylogeographic structure, with intraspecific diversification dating to ca. 0.16
      and 0.37 Ma, respectively. Mid-Pleistocene-age phylogeographic structure was
      found within two smaller-bodied species (A. strepitans - 1.16 Ma, N. sericea -
      1.36 Ma] inhabiting dry open habitats. Branches separating independently evolving
      species were long compared to intraspecific branches. Ecological niche models
      hindcast to the Last Glacial Maximum (LGM) matched expectations from the genetic
      datasets for A. zelandica and A. strepitans, suggesting that the range of A.
      zelandica was greatly reduced while A. strepitans refugia were more extensive.
      However, no LGM habitat could be reconstructed for A. cingulata and N. sericea,
      suggesting survival in microhabitats not detectable with our downscaled climate
      data. CONCLUSIONS: Unlike the large and continuous diversification exhibited by
      the Kikihia-Maoricicada-Rhodopsalta clade, the contemporaneous Amphipsalta
      Notopsalta lineage contains four comparatively old (early branching) species that
      show only recent diversification. This indicates either a long period of stasis
      with no speciation, or one or more bouts of extinction that have pruned the
      radiation. Within Amphipsalta-Notopsalta, greater population structure is found
      in dry-open-habitat species versus forest specialists. We attribute this
      difference to the fact that NZ lowland forests were repeatedly reduced in extent
      during glacial periods, while steep, open habitats likely became more available
      during late Pleistocene uplift.

PMID- 22967049
TI  - Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9
      signaling pathway.
AB  - BACKGROUND: The prognosis of human glioma is poor, and the highly invasive nature
      of the disease represents a major impediment to current therapeutic modalities.
      The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1
      protein (Bmi-1) has been linked to the development and progression of glioma;
      however, the biological role of Bmi-1 in the invasion of glioma remains unclear.
      METHODS: A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via
      stable transfection or to be silenced for Bmi-1 expression using RNA interfering
      method. Migration and invasiveness of the engineered cells were assessed using
      wound healing assay, Transwell migration assay, Transwell matrix penetration
      assay and 3-D spheroid invasion assay. MMP-9 expression and activity were
      measured using real-time PCR, ELISA and the gelatin zymography methods.
      Expression of NF-kappaB target genes was quantified using real-time PCR. NF
      kappaB transcriptional activity was assessed using an NF-kappaB luciferase
      reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed
      using immunohistochemical assay. RESULTS: Ectopic overexpression of Bmi-1
      dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the
      invasiveness and migration of glioma cells. NF-kappaB transcriptional activity
      and MMP-9 expression and activity were significantly increased in Bmi-1
      overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase
      activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on
      the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB
      signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells.
      Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation
      as well as MMP-9 expression in clinical glioma samples. CONCLUSIONS: Bmi-1 may
      play an important role in the development of aggressive phenotype of glioma via
      activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel
      therapeutic target for glioma.

PMID- 22967050
TI  - Suppression of alpha-amylase genes improves quality of rice grain ripened under
      high temperature.
AB  - High temperature impairs rice (Oryza sativa) grain filling by inhibiting the
      deposition of storage materials such as starch, resulting in mature grains with a
      chalky appearance, currently a major problem for rice farming in Asian countries.
      Such deterioration of grain quality is accompanied by the altered expression of
      starch metabolism-related genes. Here we report the involvement of a starch
      hydrolyzing enzyme, alpha-amylase, in high temperature-triggered grain
      chalkiness. In developing seeds, high temperature induced the expression of alpha
      amylase genes, namely Amy1A, Amy1C, Amy3A, Amy3D and Amy3E, as well as alpha
      amylase activity, while it decreased an alpha-amylase-repressing plant hormone,
      ABA, suggesting starch to be degraded by alpha-amylase in developing grains under
      elevated temperature. Furthermore, RNAi-mediated suppression of alpha-amylase
      genes in ripening seeds resulted in fewer chalky grains under high-temperature
      conditions. As the extent of the decrease in chalky grains was highly correlated
      to decreases in the expression of Amy1A, Amy1C, Amy3A and Amy3B, these genes
      would be involved in the chalkiness through degradation of starch accumulating in
      the developing grains. The results show that activation of alpha-amylase by high
      temperature is a crucial trigger for grain chalkiness and that its suppression is
      a potential strategy for ameliorating grain damage from global warming.

PMID- 22967051
TI  - Community resilience and decision theory challenges for catastrophic events.
AB  - Extreme and catastrophic events pose challenges for normative models of risk
      management decision making. They invite development of new methods and principles
      to complement existing normative decision and risk analysis. Because such events
      are rare, it is difficult to learn about them from experience. They can prompt
      both too little concern before the fact, and too much after. Emotionally charged
      and vivid outcomes promote probability neglect and distort risk perceptions.
      Aversion to acting on uncertain probabilities saps precautionary action; moral
      hazard distorts incentives to take care; imperfect learning and social adaptation
      (e.g., herd-following, group-think) complicate forecasting and coordination of
      individual behaviors and undermine prediction, preparation, and insurance of
      catastrophic events. Such difficulties raise substantial challenges for normative
      decision theories prescribing how catastrophe risks should be managed. This
      article summarizes challenges for catastrophic hazards with uncertain or
      unpredictable frequencies and severities, hard-to-envision and incompletely
      described decision alternatives and consequences, and individual responses that
      influence each other. Conceptual models and examples clarify where and why new
      methods are needed to complement traditional normative decision theories for
      individuals and groups. For example, prospective and retrospective preferences
      for risk management alternatives may conflict; procedures for combining
      individual beliefs or preferences can produce collective decisions that no one
      favors; and individual choices or behaviors in preparing for possible disasters
      may have no equilibrium. Recent ideas for building "disaster-resilient"
      communities can complement traditional normative decision theories, helping to
      meet the practical need for better ways to manage risks of extreme and
      catastrophic events.

PMID- 22967052
TI  - Amine modification of thermally carbonized porous silicon with silane coupling
      chemistry.
AB  - Thermally carbonized porous silicon (TCPSi) microparticles were chemically
      modified with organofunctional alkoxysilane molecules using a silanization
      process. Before the silane coupling, the TCPSi surface was activated by immersion
      in hydrofluoric acid (HF). Instead of regeneration of the silicon hydride
      species, the HF immersion of silicon carbide structure forms a silanol
      termination (Si-OH) on the surface required for silanization. Subsequent
      functionalization with 3-aminopropyltriethoxysilane provides the surface with an
      amine (-NH(2)) termination, while the SiC-type layer significantly stabilizes the
      functionalized structure both mechanically and chemically. The presence of
      terminal amine groups was verified with FTIR, XPS, CHN analysis, and
      electrophoretic mobility measurements. The overall effects of the silanization to
      the morphological properties of the initial TCPSi were analyzed and they were
      found to be very limited, making the treatment effects highly predictable. The
      maximum obtained number of amine groups on the surface was calculated to be 1.6
      groups/nm(2), corresponding to 79% surface coverage. The availability of the
      amine groups for further biofunctionalization was confirmed by successful
      biotinylation. The isoelectric point (IEP) of amine-terminated TCPSi was measured
      to be at pH 7.7, as opposed to pH 2.6 for untreated TCPSi. The effects of the
      surface amine termination on the cell viability of Caco-2 and HT-29 cells and on
      the in vitro fenofibrate release profiles were also assessed. The results
      indicated that the surface modification did not alter the loading of the drug
      inside the pores and also retained the beneficial enhanced dissolution
      characteristics similar to TCPSi. Cellular viability studies also showed that the
      surface modification had only a limited effect on the biocompatibility of the
      PSi.

PMID- 22967053
TI  - Emil Theodor Kocher--valve surgery for epilepsy.
AB  - Emil Theodor Kocher (1841-1917) was a pioneering and versatile Swiss surgeon who
      played a decisive role in the surgical evolution on the threshold to the 20th
      century. Apart from conducting intense research and fostering the development of
      the surgical treatment of thyroid gland diseases (honored with a Nobel Prize in
      1909), he remained a generalist and was active in orthopedic, genitourinary, and
      neurologic surgery. Even today, many surgical techniques and instruments are
      still named after him, thus providing evidence of his great impact. His
      neurosurgical ambitions included, in particular, cerebral and spinal trauma, the
      pathophysiology of elevated intracranial pressure, as well as etiological
      considerations and the operative treatment of epilepsy. This article aims to shed
      light on Kocher's work on epilepsy, published exclusively in German, and
      illustrates the development of his idea on valve surgery for recurrent general
      convulsions.

PMID- 22967054
TI  - The Red flag! risk assessment among medical homeopaths in Norway: a qualitative
      study.
AB  - BACKGROUND: Homeopathy is widely used, and many European physicians practice
      homeopathy in addition to conventional medicine. Adverse effects in homeopathy
      are not expected by homeopaths due to the negligible quantities of active
      substances in a remedy. However, we questioned if homeopathic aggravation, which
      is described as a temporary worsening of existing symptoms following a correct
      homeopathic remedy, should be regarded as adverse effects or ruled out as
      desirable events of the treatment. In order to improve knowledge in an unexplored
      area of patient safety, we explored how medical homeopath discriminate between
      homeopathic aggravations and adverse effects, and how they assessed patient
      safety in medical practice. METHOD: A qualitative approach was employed using
      focus group interviews. Two interviews with seven medical homeopaths were
      performed in Oslo, Norway. The participants practiced homeopathy besides
      conventional medicine. Qualitative content analysis was used to analyze the text
      data. The codes were defined before and during the data analysis. RESULTS:
      According to the medical homeopaths, a feeling of well-being may be a criterion
      to distinguish homeopathic aggravations from adverse effects. There was
      disagreement among the participants whether or not homeopathic treatment produced
      adverse effects. However, they agreed when an incorrect remedy was administrated,
      it may create a disruption or suppressive reaction in the patient. This was not
      perceived as adverse effects but a possibility to prescribe a new remedy as new
      symptoms emerge. This study revealed several advantages for the patients as the
      medical homeopaths looked for dangerous symptoms which may enhance safety. The
      patient was given time and space, which enabled the practitioner to see the
      complete picture. A more comprehensive toolkit gave the medical homeopaths a
      feeling of professionalism. CONCLUSION: This explorative study investigated how
      Medical Homeopaths understood and assessed risk in their clinical practice. A
      feeling of well-being emerging soon after taking the remedy was the most
      important criterion for discriminating between Homeopathic Aggravations and
      Adverse Effects in clinical practice. The Medical Homeopaths used the view of
      both professions and always looked for red flag situations in the consultation
      room. They combined knowledge from two treatment systems which may have
      advantages for the patient. These tentative results deserve further research
      efforts to improve patient safety among users of homeopathy. For further research
      we find it important to improve and develop concepts that are unique to
      homeopathy in order to validate and modernize this medical practice.

PMID- 22967055
TI  - Incidence, prevalence, and hybrid approaches to calculating disability-adjusted
      life years.
AB  - When disability-adjusted life years are used to measure the burden of disease on
      a population in a time interval, they can be calculated in several different
      ways: from an incidence, pure prevalence, or hybrid perspective. I show that
      these calculation methods are not equivalent and discuss some of the formal
      difficulties each method faces. I show that if we don't discount the value of
      future health, there is a sense in which the choice of calculation method is a
      mere question of accounting. Such questions can be important, but they don't
      raise deep theoretical concerns. If we do discount, however, choice of
      calculation method can change the relative burden attributed to different
      conditions over time. I conclude by recommending that studies involving
      disability-adjusted life years be explicit in noting what calculation method is
      being employed and in explaining why that calculation method has been chosen.

PMID- 22967056
TI  - Density variant glycan microarray for evaluating cross-linking of mucin-like
      glycoconjugates by lectins.
AB  - Interactions of mucin glycoproteins with cognate receptors are dictated by the
      structures and spatial organization of glycans that decorate the mucin
      polypeptide backbone. The glycan-binding proteins, or lectins, that interact with
      mucins are often oligomeric receptors with multiple ligand binding domains. In
      this work, we employed a microarray platform comprising synthetic glycopolymers
      that emulate natural mucins arrayed at different surface densities to evaluate
      how glycan valency and spatial separation affect the preferential binding mode of
      a particular lectin. We evaluated a panel of four lectins (Soybean agglutinin
      (SBA), Wisteria floribunda lectin (WFL), Vicia villosa-B-4 agglutinin (VVA), and
      Helix pomatia agglutin (HPA)) with specificity for alpha-N-acetylgalactosamine
      (alpha-GalNAc), an epitope displayed on mucins overexpressed in many
      adenocarcinomas. While these lectins possess the ability to agglutinate A(1)
      blood cells carrying the alpha-GalNAc epitope and cross-link low valency
      glycoconjugates, only SBA showed a tendency to form intermolecular cross-links
      among the arrayed polyvalent mucin mimetics. These results suggest that
      glycopolymer microarrays can reveal discrete higher-order binding preferences
      beyond the recognition of individual glycan epitopes. Our findings indicate that
      glycan valency can set thresholds for cross-linking by lectins. More broadly,
      well-defined synthetic glycopolymers enable the integration of glycoconjugate
      structural and spatial diversity in a single microarray screening platform.

PMID- 22967057
TI  - The role of R.E.N.A.L. nephrometry score in the era of robot-assisted partial
      nephrectomy.
AB  - PURPOSE: We studied the role of the R.E.N.A.L. nephrometry score (NS) in
      predicting surgical outcomes in a series of robot-assisted partial nephrectomy
      (RAPN). PATIENTS AND METHODS: Of 99 cases of minimally invasive partial
      nephrectomy performed by a single surgeon from 2003 to 2011, 83 were performed
      with robotic assistance. A trained physician investigator applied the NS to these
      83 cases using the preoperative CT scans. Forty-two of these were reviewed by a
      urology resident to eliminate interobserver variation. Tumors were categorized
      into noncomplex (NS 4-6) or complex (NS 7-12) tumors, and perioperative outcomes
      were compared. Outcomes were also compared by each component of the NS.
      Perioperative outcomes were analyzed using chi-square tests and Mann
      Whitney/Kruskal-Wallis tests. Univariate regression was used to analyze trends
      between nephrometry and outcomes. RESULTS: Strong correlation was found between
      the two sets of NS (Spearman correlational coefficient 0.814, P<0.001). Comparing
      between noncomplex and complex tumors, statistical differences were found in
      operative time (181 min vs 215 min, P=0.028) and ischemia time (21 min vs 24 min,
      P=0.006). Complication rates, blood loss, conversion rate, and decrease in
      glomerular filtration rate were similar in both groups. On univariate regression
      analysis, only warm ischemia time showed a significant trend with the overall NS
      (P=0.007) and the location score (P=0.031). CONCLUSIONS: A high NS was not
      associated with clinically worse outcomes during RAPN. Such renal tumors can
      still be excised safely with robotic assistance without adverse long-term
      effects.

PMID- 22967058
TI  - Domestication of honey bees was associated with expansion of genetic diversity.
AB  - Humans have been keeping honey bees, Apis mellifera, in artificial hives for over
      7000 years. Long enough, one might imagine, for some genetic changes to have
      occurred in domestic bees that would distinguish them from their wild ancestors.
      Indeed, some have argued that the recent mysterious and widespread losses of
      commercial bee colonies, are due in part to inbreeding. In this issue of
      Molecular Ecology, Harpur et al. (2012) show that the domestication of honey
      bees, rather than reducing genetic variance in the population, has increased it.
      It seems that the commercial honey bees of Canada are a mongrel lot, with far
      more variability than their ancestors in Europe.

PMID- 22967059
TI  - Rice domestication: histories and mysteries.
AB  - Domesticated rice (Oryza sativa) is one of the world's most important food crops,
      culturally, nutritionally and economically (Khush 1997). Thus, it is no surprise
      that there is intense curiosity about its genetic and geographical origins, its
      response to selection under domestication, and the genetic structure of its wild
      relative, Oryza rufipogon. Studies of Oryza attempting to answer these questions
      have accompanied each stage of the development of molecular markers, starting
      with allozymes and continuing to genome sequencing. While many of these studies
      have been restricted to small sample sizes, in terms of either the number of
      markers used or the number and distribution of the accessions, costs are now low
      enough that researchers are including large numbers of molecular markers and
      accessions. How will these studies relate to previous findings and long-held
      assumptions about rice domestication and evolution? If the paper in this issue of
      Molecular Ecology (Huang et al. 2012) is any indication, there will be some
      considerable surprises in store. In this study, a geographically and genomically
      thorough sampling of O. rufipogon and O. sativa revealed two genetically distinct
      groups of wild rice and also indicated that only one of these groups appears to
      be related to domesticated rice. While this fits well with previous studies
      indicating that there are genetic subdivisions within O. rufipogon, it stands in
      contrast to previous findings that the two major varieties of O. sativa (indica
      and japonica) were domesticated from two (or more) subpopulations of wild rice.

PMID- 22967060
TI  - Midterm results of surgery for adults with congenital heart disease centralized
      to a Swedish cardiothoracic center.
AB  - OBJECTIVE: The surgical management of adults with congenital heart disease (ACHD)
      offers a great challenge, with a large number of anomalies with complex
      pathophysiology necessitating specific treatments. Pre- and postoperative
      morbidity has been relatively high, and the influencing factors are not
      completely identified. We sought to evaluate the incidence and predictors of
      postoperative complications following surgery for ACHD centralized to a Swedish
      cardiothoracic center. DESIGN: Between April 2003 and May 2012, 191 consecutive
      patients with ACHD underwent 192 surgical procedures at our department. Pre-,
      intra-, and postoperative data were prospectively entered in a clinical database
      and retrospectively reviewed. Multivariate analysis was used to identify
      determinants of postoperative complications as a composite end point. RESULTS:
      The 30-day mortality was 0.5%. Overall survival was 98.3% +/- 1.0 at 1 year and
      98.3% +/- 1.0 at 5 years postoperatively. Repeat sternotomy had to be performed
      in 94 patients (49%). New onset atrial fibrillation or flutter was the most
      prevalent (13%, n = 17/135) postoperative complication. Independent risk factors
      for major postoperative complications were age (odds ratio [OR] 1.81/10 year
      increment, P = 0.001; 95% confidence interval [CI] 1.29-2.53), reduced (<50%)
      systemic left ventricle ejection fraction (OR 3.61, P = 0.031; 95% CI 1.13-11.6),
      and the duration of cardiopulmonary bypass (OR 3.34/60 minute increase, P <
      0.001; 95% CI 2.03-5.49). CONCLUSIONS: Our present data suggest that surgery in
      ACHD can be performed in centralized units with an excellent early and midterm
      survival. The incidence of postoperative complications was relatively low
      consisting mainly of supraventricular arrhythmias. In our opinion, ACHD surgery
      should be performed in centralized units with experienced surgeons in a dedicated
      multidisciplinary team for optimized postoperative management.

PMID- 22967061
TI  - New insights into pre-mRNA processing factor 19: A multi-faceted protein in
      humans.
AB  - During the dynamic assembly and activation of the spliceosome, human pre-mRNA
      processing factor 19 (hPrp19) plays a major role alone or as a part of a protein
      complex. In addition to participating in post-transcriptional regulation of
      eukaryotic gene, hPrp19 takes part in many physiological events such as ubiquitin
      proteasome system, DNA damage response, proliferation and apoptosis. Increasing
      evidence also indicates a potential role of hPrp19 during oncogenesis, possibly
      owing to its activity of repressing apoptosis. Together, these studies add a new
      dimension to our understanding of hPrp19, and we have reason to believe that
      continuing excavation of this multi-faceted protein may shed light on its roles
      in human diseases, especially in cancer.

PMID- 22967062
TI  - Mice heterozygous for the oxytocin receptor gene (Oxtr(+/-)) show impaired social
      behaviour but not increased aggression or cognitive inflexibility: evidence of a
      selective haploinsufficiency gene effect.
AB  - We characterised the behavioural phenotype of mice heterozygous (Oxtr(+/-)) for
      the oxytocin receptor gene (Oxtr) and compared it with that of Oxtr null mice
      (Oxtr(-/-)), which display autistic-like behaviours, including impaired
      sociability and preference for social novelty, impaired cognitive flexibility,
      and increased aggression. Similar to Oxtr(-/-) mice, the Oxtr(+/-) showed
      impaired sociability and preference for social novelty but, unlike the null
      genotype, their cognitive flexibility and aggression were normal. By
      autoradiography, Oxtr(+/-) mice were found to have approximately 50% fewer
      oxytocin receptors (OXTRs) in all of the examined brain regions. Thus, because a
      partial reduction in Oxtr gene expression is sufficient to compromise social
      behaviour, the Oxtr acts as a haploinsufficient gene. Furthermore, the
      inactivation of the Oxtr gene affects specific behaviours in a dose-dependent
      manner: social behaviour is sensitive to even a partial reduction in Oxtr gene
      expression, whereas defects in aggression and cognitive flexibility require the
      complete inactivation of the Oxtr gene to emerge. We then investigated the rescue
      of the Oxtr(+/-) social deficits by oxytocin (OT) and Thr(4)Gly(7)OT (TGOT)
      administered i.c.v. at different doses. TGOT was more potent than OT in rescuing
      sociability and social novelty in both genotypes. Furthermore, the TGOT doses
      that reverted impaired sociability and preference for social novelty in Oxtr(+/-)
      were lower than those required in Oxtr(-/-), thus suggesting that the rescue
      effect is mediated by OXTR in Oxtr(+/-) and by other receptors (presumably
      vasopressin V1a receptors) in Oxtr(-/-). In line with this, a low dose of the
      selective oxytocin antagonist desGlyDTyrOVT blocks the rescue effect of TGOT only
      in the Oxtr(+/-) genotype, whereas the less selective antagonist SR49059 blocks
      rescue in both genotypes. In conclusion, the Oxtr(+/-) mouse is a unique animal
      model for investigating how partial loss of the Oxtr gene impair social
      interactions, and for designing pharmacological rescue strategies.

PMID- 22967063
TI  - Mitochondrial genome of the Shorthead catfish (Pelteobagrus eupogon).
AB  - The complete mitochondrial genome of Shorthead catfish (Pelteobagrus eupogon) was
      obtained by DNA sequencing based on the PCR fragments. The entire genome was
      16,562 bp in length, with a gene content of 13 protein-coding, 2 ribosomal RNA,
      and 22 transfer RNA genes, and order identical to that observed in most other
      vertebrates. Those genes are arranged compactly with no introns and few
      intergenic nucleotides. Molecular data here presented provide a useful toll for
      evolutionary as well as population genetic studied.

PMID- 22967064
TI  - Immunotoxicity of the organochlorine pesticide methoxychlor in female ICR,
      BALB/c, and C3H/He mice.
AB  - Several types of pesticides, including organochlorines, are known to suppress or
      modulate immune responses. The present study evaluated the immunotoxicity of the
      organochlorine pesticide methoxychlor (MXC) in female BALB/c, C3H/He, and ICR
      mice. Mice were given oral MXC doses of 0, 30, 100, and 300 mg/kg each day for 7
      consecutive days. On day 4, the mice also received an intravenous injection of
      sheep red blood cells (SRBC). The splenic plaque-forming cell (PFC) IgM response
      and the serum anti-SRBC IgM antibody titer were evaluated while splenic
      lymphocytes were counted by flow cytometry and the spleen underwent
      histopathological analysis. Significant decreases in IgM PFC responses were seen
      in BALB/c, C3H/He, and ICR mice that received MXC doses of 100 and 300 mg/kg.
      Similar changes in serum anti-SRBC IgM antibody titers occurred in three strain
      mice. Flow cytometric analysis revealed significantly decreased splenic T-cell
      (CD3+) populations in a dose dependent manner in BALB/c mice, and in the 300
      mg/kg of MXC-treated group of C3H/He mice. Germinal center (GC) B-cell
      (CD19+PNA+) populations were significantly decreased in the 300 mg/kg of MXC
      treated groups of all three mouse strains and in the 30 and 100 mg/kg of MXC
      treated groups of BALB/c and C3H/He strain mice. Histopathological analysis
      revealed decreased cellularity of the periarteriolar lymphoid sheath (PALS; T
      cell area) and decreased GC development in all three strains of mice treated with
      300 mg/kg MXC. These results suggest that MXC has an immune-suppressive effect in
      mice, and that our protocol may be useful for rapidly detecting immunosuppression
      induced by environmental chemicals.

PMID- 22967065
TI  - Urine phthalate concentrations are higher in people with stroke: United States
      National Health and Nutrition Examination Surveys (NHANES), 2001-2004.
AB  - BACKGROUND AND PURPOSE: Associations between plastic-associated chemicals, such
      as bisphenol A, and cardiovascular disease have begun to emerge in the current
      century. However, the relationship between urine phthalates and risk of stroke is
      unclear. It was aimed to study the relationship between urine phthalate
      concentrations and risk of stroke in a national population-based cross-sectional
      study. METHODS: Data were retrieved from United States National Health and
      Nutrition Examination Surveys, 2001-2004, including demographics, self-reported
      medical conditions (stroke status) and urine phthalate concentrations. Analyses
      involved t-test and logistic regression models. RESULTS: Of 13 phthalate
      concentrations, the mean values of mono-n-butyl phthalate (2001-2002: 131.27 +/-
      685.62 and 43.02 +/- 117.70, P=0.0001; 2003-2004: 114.36 +/- 555.41 and 49.48 +/-
      153.53, P=0.008) and mono-(3-carboxypropyl) phthalate (2001-2002: 13.60 +/- 37.05
      and 5.48 +/- 10.55, P<0.001; 2003-2004: 10.56 +/- 38.37 and 5.94 +/- 14.76,
      P=0.038) concentrations were found significantly higher in people with stroke. It
      was also observed that low doses of mono-n-butyl phthalate (OR 1.0009, 95%CI
      0.999-1.003, P=0.266 in 2001-2002, and OR 1.0010, 95%CI 1.0001-1.0019, P=0.028 in
      2003-2004) and mono-(3-carboxypropyl) phthalate (OR 1.03, 95%CI 1.00-1.05,
      P=0.055 in 2001-2002, and OR 1.004, 95% CI 1.00-1.01 P=0.240 in 2003-2004) were
      associated with higher risk of stroke after full adjustments. CONCLUSIONS: Urine
      phthalate concentrations are potentially associated with increased risk of
      stroke, although the causality cannot be established in the current cross
      sectional study design. Future longitudinal cohort studies and/or clinical trials
      are warranted to understand the biological mechanism along the pathway before
      drawing a firm conclusion on the relationship between phthalates and risk of
      stroke in humans.

PMID- 22967066
TI  - Two-piece nasal septum prosthesis for a large nasal septum perforation: a
      clinical report.
AB  - Nasal septum perforation presents with the symptoms of epistaxis and crusting.
      Obturation of the defect will decrease the symptoms and increase patient comfort.
      Prosthetic closure is more predictable and thus the treatment of choice in larger
      defects. This article describes a procedure for construction of a magnet
      retained, heat-processed acrylic nasal septum prosthesis. The two-piece nasal
      septum prosthesis was processed and joined together in situ by magnets. Each
      piece of the septum prosthesis conforms to the remaining medial wall of each
      nostril and forms the missing half of the nasal septum. The prosthesis not only
      alleviates symptoms, but also provides structural support to the saddle-shaped
      nose and improves esthetics.

PMID- 22967067
TI  - Molecular dynamics study of anhydrous lamellar structures of synthetic
      glycolipids: effects of chain branching and disaccharide headgroup.
AB  - Glycolipids form materials of considerable potential for a wide range of
      surfactant and thin film applications. Understanding the effect of glycolipid
      covalent structure on the properties of their thermotropic and lyotropic
      assemblies is a key step toward rational design of new glycolipid-based
      materials. Here, we perform molecular dynamics simulations of anhydrous bilayers
      of dodecyl beta-maltoside, dodecyl beta-cellobioside, dodecyl beta-isomaltoside,
      and a C(12)C(10) branched beta-maltoside. Specifically, we examine the
      consequences of chain branching and headgroup identity on the structure and
      dynamics of the lamellar assemblies. Chain branching of the glycolipid leads to
      measurable differences in the dimensions and interactions of the lamellar
      assembly, as well as a more fluid-like hydrophobic chain region. Substitution of
      the maltosyl headgroup of betaMal-C(12) by an isomaltosyl moiety leads to a
      significant decrease in bilayer spacing as well as a markedly altered pattern of
      inter-headgroup hydrogen bonding. The distinctive simulated structures of the two
      regioisomers provide insight into the difference of ~90  degrees C in their
      observed clearing temperatures. For all four simulated glycolipid systems, with
      the exception of the sn-2 chain of the branched maltoside, the alkyl chains are
      ordered and exhibit a distinct tilt, consistent with recent crystallographic
      analysis of a branched chain Guerbet glycoside. These insights into structure
      property relationships from simulation provide an important molecular basis for
      future design of synthetic glycolipid materials.

PMID- 22967068
TI  - New WS9326A congeners from Streptomyces sp. 9078 inhibiting Brugia malayi
      asparaginyl-tRNA synthetase.
AB  - Lymphatic filariasis is caused by the Brugia malayi parasite. Three new congeners
      of the depsipeptide WS9326A (1), WS9326C (2), WS9326D (3), and WS9326E (4), were
      isolated from Streptomyces sp. 9078 by using a B. malayi asparaginyl-tRNA
      synthetase (BmAsnRS) inhibition assay. WS9326D specifically inhibits the BmAsnRS,
      kills the adult B. malayi parasite, and does not exhibit significant general
      cytotoxicity to human hepatic cells, representing a new lead scaffold for
      antifilarial drug discovery.

PMID- 22967070
TI  - Nanocomposite coatings on biomedical grade stainless steel for improved corrosion
      resistance and biocompatibility.
AB  - The 316 L stainless steel is one of the most commonly available commercial
      implant materials with a few limitations in its ease of biocompatibility and long
      standing performance. Hence, porous TiO(2)/ZrO(2) nanocomposite coated over 316 L
      stainless steels was studied for their enhanced performance in terms of its
      biocompatibility and corrosion resistance, following a sol-gel process via dip
      coating technique. The surface composition and porosity texture was studied to be
      uniform on the substrate. Biocompatibility studies on the TiO(2)/ZrO(2)
      nanocomposite coatings were investigated by placing the coated substrate in a
      simulated body fluid (SBF). The immersion procedure resulted in the complete
      coverage of the TiO(2)/ZrO(2) nanocomposite (coated on the surface of 316 L
      stainless steel) with the growth of a one-dimensional (1D) rod-like carbonate
      containing apatite. The TiO(2)/ZrO(2) nanocomposite coated specimens showed a
      higher corrosion resistance in the SBF solution with an enhanced
      biocompatibility, surpassing the performance of the pure oxide coatings. The cell
      viability of TiO(2)/ZrO(2) nanocomposite coated implant surface was examined
      under human dermal fibroblasts culture, and it was observed that the composite
      coating enhances the proliferation through effective cellular attachment compared
      to pristine 316 L SS surface.

PMID- 22967069
TI  - Autoimmunity to isomerized histone H2B in systemic lupus erythematosus.
AB  - Histone H2B is a common target of autoantibodies in both spontaneous and drug
      induced systemic lupus erythematosus (SLE). Recent studies demonstrate that
      Asp(25) of histone H2B (H2B) spontaneously converts to an isoaspartic acid
      (isoAsp) in vivo. Our laboratory has demonstrated that the posttranslational
      modification of an aspartic acid to an isoaspartic acid within self-peptides
      renders otherwise ignored peptides immunogenic. Analysis of serum from lupus
      prone mice and histone antibody positive SLE patients revealed antibodies
      specific to the Asp and isoAsp H2B(21-35) peptide, and that the expression of
      these antibodies is dependent on TLR9. IsoAsp H2B(21-35) is immunogenic in non
      autoimmune prone mice and mice lacking the ability to repair isoAsp have
      significantly reduced levels of antibodies to H2B. Asp H2B(21-35) incubated at
      physiological temperatures and pH acquires the isoAsp modification, demonstrating
      that H2B(21-35) is prone to spontaneous isoAsp formation in vivo. Autoimmunity to
      isoAsp H2B suggests that this form of the autoantigen may be critical in the
      induction of anti-histone autoantibodies in human SLE and in murine models of
      disease.

PMID- 22967071
TI  - Disrupting cancer cells' biocircuits with interactome-based drugs: is 'clinical'
      innovation realistic?

PMID- 22967072
TI  - Functional '-omics' in intrauterine growth restriction: novel insights into child
      development.

PMID- 22967074
TI  - MultiBac complexomics.
AB  - Recombinant production of multiprotein complexes is an emerging focus in academic
      and pharmaceutical research and is expected to play a key role in addressing
      complex biological questions in health and disease. Here we describe MultiBac, a
      state-of-the-art eukaryotic expression technology utilizing an engineered
      baculovirus to infect insect cells. The robust and flexible concept of MultiBac
      allows for simultaneous expression of multiple proteins in a single cell, which
      can be used to produce protein complexes and to recapitulate metabolic pathways.
      The MultiBac system has been set up as an open-access platform technology at the
      European Molecular Biology Laboratory (EMBL) in Grenoble, France. The performance
      of this platform and its access modalities to the scientific community are
      detailed in this article. The MultiBac system has been instrumental for unlocking
      the function of a number of essential multiprotein complexes and recent examples
      are discussed. This article presents a novel concept for the customized
      production of glycosylated protein targets using SweetBac, a modified MultiBac
      vector system. Finally, this article outlines how MultiBac may further develop in
      the future to serve applications in both academic and industrial research and
      development.

PMID- 22967075
TI  - The human urinary proteome: combinational approaches to comprehensive mapping.
AB  - The development methodologies for the assessment of the protein content of
      biological samples have been in the 'eye of the storm' in proteomics for almost
      two decades. The work of Zerefos et al. is a continuation of this trend, focusing
      on analysis of urinary proteins using a combination of separation methodologies.
      In this work, the authors employ a previously analyzed control urine sample.
      Three different methodologies are presented, involving the combination of
      classical separation approaches, such as SDS-PAGE, preparative electrophoresis
      and liquid chromatography and standard mass spectrometer instrumentation. Several
      hundred proteins were reported following the application of a typical proteomics
      workflow and the use of a data meta-analysis platform to enhance the credibility
      of the final output. This is also established through cross-method (within this
      study) as well as cross-study (comparison of this with other main studies in the
      field) data comparisons. Emphasis is placed on the presentation of experimental
      identifiers as well as information provided at the peptide level.

PMID- 22967076
TI  - Role of mass spectrometry-based proteomics in the study of cellular reprogramming
      and induced pluripotent stem cells.
AB  - The generation of human induced pluripotent stem cells (iPSCs) from
      differentiated cells holds important clinical implications. Human iPSCs represent
      the most promising resource for regenerative medicine by enabling the use of
      patient-specific cells of any lineage without the need for embryonic material.
      However, before therapeutic applications using human iPSCs are carried out,
      extensive analyses are needed to assess molecular differences and similarities
      between human iPSCs and their natural counterparts, human embryonic stem cells.
      The pluralism of mechanisms acting in a biological system can be better
      approached by studying several elements simultaneously in an unbiased manner.
      This review will discuss recent genome-wide analyses of iPSCs (e.g., transcripts
      and epigenetics) and will introduce the huge potential of mass spectrometry-based
      proteomics in decoding the unique mechanisms underlying the reprogramming process
      and the molecular nature of cellular identity.

PMID- 22967077
TI  - Affinity proteomics: the role of specific binding reagents in human proteome
      analysis.
AB  - Affinity proteomics is the field of proteome analysis based on the use of
      antibodies and other binding reagents as protein-specific detection probes. In
      this review, the particular strengths of affinity methods for determination of
      protein localization, functional characterization, biomarker discovery and
      intracellular applications, and their resulting impact in basic and clinical
      research are highlighted. An additional focus is on the requirements for
      systematic binder generation and current large-scale binder projects, including
      bioinformatic frameworks for epitope selection and for documentation of available
      binding reagents and their performance. In addition to current affinity
      proteomics methods and applications, including arrays of proteins, binders,
      lysates and tissues, approaches coupling mass spectrometry-based proteomics and
      affinity proteomics are reviewed.

PMID- 22967078
TI  - Tumor profiling using protein biomarker panels in malignant melanoma: application
      of tissue microarrays and beyond.
AB  - Despite advances in our knowledge of the disease, malignant melanoma remains an
      unpredictable entity. The revolution in molecular biological techniques, such as
      DNA sequencing and gene-expression profiling, has uncovered many potential
      protein targets and biomarkers relevant to melanoma progression. Successful
      clinical application would be aided significantly by downstream proteomic
      validation of those candidate markers using a combination of immunohistochemistry
      and tissue microarrays. Yet, research in this context seems to lag behind the
      output of genomic data relating to melanoma. In this article, we look at the
      strengths and pitfalls of tissue microarrays in malignant melanoma. We will show
      how tissue microarrays have become a vital step in the transition from molecular
      techniques to useful clinical assays and interventions and look at likely future
      developments for advances in this field.

PMID- 22967080
TI  - Potential blood biomarkers for stroke.
AB  - Stroke is one of the most common causes of death worldwide and a major cause of
      acquired disability in adults. Despite advances in research during the last
      decade, prevention and treatment strategies still suffer from significant
      limitations, and therefore new theoretical and technical approaches are required.
      Technological advances in the proteomic and metabolomic areas, during recent
      years, have permitted a more effective search for novel biomarkers and
      therapeutic targets that may allow for effective risk stratification and early
      diagnosis with subsequent rapid treatment. This review provides a comprehensive
      overview of the latest candidate proteins and metabolites proposed as new
      potential biomarkers in stroke.

PMID- 22967081
TI  - Recent advances in platelet proteomics.
AB  - Platelets are the fundamental players in primary hemostasis, but are also
      involved in several pathological conditions. The remarkable advances in proteomic
      methodologies have allowed a better understanding of the basic physiological
      pathways underlying platelet biology. In addition, recent platelet proteomics
      focused on disease conditions, helping to elucidate the molecular mechanisms of
      complex and/or unknown human disorders and to find novel biomarkers for early
      diagnosis and drug targets. The most common and innovative proteomic techniques,
      both gel-based and gel-free, used in platelet proteomics will be reviewed here. A
      particular focus will be given to studies that used a subproteomic strategy to
      analyze specific platelet conditions (resting or activated), compartments
      (membrane, granules and microparticles) or fractions (phosphoproteome or
      glycoproteome). The thousands of platelet proteins and interactions discovered so
      far by these different powerful proteomic approaches represent a precious source
      of information for both basic science and clinical applications in the field of
      platelet biology.

PMID- 22967079
TI  - Protein biomarkers of alcohol abuse.
AB  - Alcohol abuse can lead to a number of health and social issues. Our current
      inability to accurately assess long-term drinking behaviors is an important
      obstacle to its diagnosis and treatment. Biomarkers for chronic alcohol
      consumption have made a number of important advances but have yet to become
      highly accurate and as accepted as objective tests for other diseases. Thus,
      there is a crucial need for the development of more sensitive and specific
      markers of alcohol abuse. Recent advancements in proteomic technologies have
      greatly increased the potential for alcohol abuse biomarker discovery. Here, the
      authors review established and novel protein biomarkers for long-term alcohol
      consumption and the proteomic technologies that have been used in their study.

PMID- 22967082
TI  - Application of one- and two-dimensional NMR spectroscopy for the characterization
      of Protected Designation of Origin Lambrusco wines of Modena.
AB  - Lambrusco is a Protected Designation of Origin (PDO) red wine of Modena (Italy)
      produced according to the production regulation (Decreto Ministeriale (DM) July
      27, 2009; GU no. 184-187-188, 13/08/2009). Here the use of (1)H NMR spectroscopy
      as molecular fingerprints of several PDO Lambrusco wines was proposed to serve as
      indicators of authenticity and quality control. Application of partial least
      squares discriminant analysis (PLS-DA) revealed a good varietal discrimination by
      analyzing the low-frequency spectral region. This model explains 68.8% of the
      variance for the Y vector (classification factor: varietal source). In
      particular, the signals of 2,3-butanediol, lactic, succinic and malic acids, and
      threonine were found to be the most statistically significant variables in the
      model. These findings seem to be very promising in the attempt to extend the
      study to geographical discrimination.

PMID- 22967083
TI  - Protein instability and functional defects caused by mutations of dihydro-orotate
      dehydrogenase in Miller syndrome patients.
AB  - Miller syndrome is a recessive inherited disorder characterized by postaxial
      acrofacial dysostosis. It is caused by dysfunction of the DHODH (dihydroorotate
      dehydrogenase) gene, which encodes a key enzyme in the pyrimidine de novo
      biosynthesis pathway and is localized at mitochondria intermembrane space. We
      investigated the consequence of three missense mutations, G202A, R346W and R135C
      of DHODH, which were previously identified in patients with Miller syndrome.
      First, we established HeLa cell lines stably expressing DHODH with Miller
      syndrome-causative mutations: G202A, R346W and R135C. These three mutant proteins
      retained the proper mitochondrial localization based on immunohistochemistry and
      mitochondrial subfractionation studies. The G202A, R346W DHODH proteins showed
      reduced protein stability. On the other hand, the third one R135C, in which the
      mutation lies at the ubiquinone-binding site, was stable but possessed no
      enzymatic activity. In conclusion, the G202A and R346W mutation causes deficient
      protein stability, and the R135C mutation does not affect stability but impairs
      the substrate-induced enzymatic activity, suggesting that impairment of DHODH
      activity is linked to the Miller syndrome phenotype.

PMID- 22967084
TI  - Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells
      following intracellular uptake of (99m)Tc versus (188)Re.
AB  - PURPOSE: Cellular radionuclide uptake increases the heterogeneity of absorbed
      dose to biological structures. Dose increase depends on uptake yield and emission
      characteristics of radioisotopes. We used an in vitro model to compare the impact
      of cellular uptake of (188)Re-perrhenate and (99m)Tc-pertechnetate on cellular
      survival. MATERIALS AND METHODS: Rat thyroid PC Cl3 cells in culture were
      incubated with (188)Re or (99m)Tc in the presence or absence of perchlorate for 1
      hour. Clonogenic cell survival was measured by colony formation. In addition,
      intracellular radionuclide uptake was quantified. RESULTS: Dose effect curves
      were established for (188)Re and (99m)Tc for various extra- and intracellular
      distributions of the radioactivity. In the presence of perchlorate, no uptake of
      radionuclides was detected and (188)Re reduced cell survival more efficiently
      than (99m)Tc. A(37), the activity that is necessary to yield 37% cell survival
      was 14 MBq/ml for (188)Re and 480 MBq/ml for (99m)Tc. In the absence of
      perchlorate, both radionuclides showed similar uptakes; however, A(37) was
      reduced by 30% for the beta-emitter and by 95% for (99m)Tc. The dose D(37) that
      yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides.
      CONCLUSIONS: Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular
      (99m)Tc yielded a dose increase that was higher compared to (188)Re due to
      emitted Auger and internal conversion-electrons. Up to 5 Gy there was no
      difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy
      intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non
      uniform lognormal radionuclide uptake.

PMID- 22967085
TI  - Albumin is taken up by hippocampal NG2 cells and astrocytes and decreases gap
      junction coupling.
AB  - PURPOSE:   Dysfunction of the blood-brain barrier (BBB) and albumin extravasation
      have been suggested to play a role in the etiology of human epilepsy. In this
      context, dysfunction of glial cells attracts increasing attention. Our study was
      aimed to analyze in the hippocampus (1) which cell types internalize albumin
      injected into the lateral ventricle in vivo, (2) whether internalization into
      astrocytes impacts their coupling and expression of connexin 43 (Cx43), and (3)
      whether expression of Kir4.1, the predominating astrocytic K(+) channel subunit,
      is altered by albumin. METHODS:   The patch-clamp method was combined with single
      cell tracer filling to investigate electrophysiologic properties and gap junction
      coupling (GJC). For cell identification, mice with cell type-specific expression
      of a fluorescent protein (NG2kiEYFP mice) and immunohistochemistry were employed.
      Semiquantitative real time polymerase chain reaction (RT-PCR) allowed analysis of
      Kir4.1 and Cx43 transcript levels. KEY FINDINGS:   We show that fluorescently
      labeled albumin is taken up by astrocytes, NG2 cells, and neurons, with NG2 cells
      standing out in terms of the quantity of uptake. Within 5 days postinjection
      (dpi), intracellular albumin accumulation was largely reduced suggesting rapid
      degradation. Electrophysiologic analysis of astrocytes and NG2 cells revealed no
      changes in their membrane properties at either time point. However, astrocytic
      GJC was significantly decreased at 1 dpi but returned to control levels within 5
      dpi. We found no changes in hippocampal Cx43 transcript expression, suggesting
      that other mechanisms account for the observed changes in coupling. Kir4.1 mRNA
      was regulated oppositely in the CA1 stratum radiatum, with a strong increase at 1
      dpi followed by a decrease at 5 dpi. SIGNIFICANCE:   The present study
      demonstrates that extravasal albumin in the hippocampus induces rapid changes of
      astrocyte function, which can be expected to impair ion and transmitter
      homeostasis and contribute to hyperactivity and epileptogenesis. Therefore,
      astrocytes may represent alternative targets for antiepileptic therapeutic
      approaches.

PMID- 22967086
TI  - Asymmetric gene introgression in two closely related Orchis species: evidence
      from morphometric and genetic analyses.
AB  - BACKGROUND: In food-deceptive orchids of the genera Anacamptis, Neotinea and
      Orchis floral isolation has been shown to be weak, whereas late-acting
      reproductive barriers are mostly strong, often restricting hybridization to the
      F1 generation. Only in a few species hybridization extends beyond the F1
      generation, giving rise to hybrid swarms. However, little is known about the
      abundance of later-generation hybrids and what factors drive their occurrence in
      hybrid populations. In this study, molecular analyses were combined with detailed
      morphological measurements in a hybrid population of two closely related Orchis
      species (Orchis militaris and O. purpurea) to investigate the hypothesis that the
      abundance of later-generation hybrids is driven by changes in floral characters
      after hybridization that exert selective pressures that in turn affect
      hybridization. RESULTS: Both the molecular and morphological data point to
      extensive genetic and morphological homogenization and asymmetric introgression.
      Estimating genomic clines from the multi-locus genotype data and testing for
      deviation from neutrality revealed that 30 out of 113 (27%) AFLP markers
      significantly deviated from neutral expectations. Plants with large floral
      displays or plant with flowers that resembled more O. purpurea had higher female
      fitness than plants with small floral displays or plants with flowers resembling
      more O. militaris, suggesting that directional selection may have contributed to
      the observed patterns of introgression. CONCLUSIONS: These results indicate that
      in closely related orchid species hybridization and gene introgression may be
      partly driven by selection for floral traits of one of the parental types.
      However, because some pure individuals were still present in the studied
      population, the parental species appeared to be sufficiently isolated to survive
      the challenge of sympatry.

PMID- 22967087
TI  - Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is
      associated with recurrent disease.
AB  - BACKGROUND: Ovarian cancer is a heterogeneous disease and prognosis for
      apparently similar cases of ovarian cancer varies. Recurrence of the disease in
      early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is
      comparable to those with recurrent advanced-stage disease. The aim of this study
      was to investigate if there are specific genomic aberrations that may explain
      recurrence and clinical outcome. METHODS: Fifty-one women with early stage serous
      ovarian cancer were included in the study. DNA was extracted from formalin fixed
      samples containing tumor cells from ovarian tumors. Tumor samples from thirty
      seven patients were analysed for allele-specific copy numbers using OncoScan
      single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool
      Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of
      heterozygosity that associated with recurrent disease were identified. RESULTS:
      The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were
      identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19
      genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were
      potential candidate genes associated with clinical outcome. LOH at 19q (51-56
      Mbp) was associated with shorter disease-free survival and was an independent
      prognostic factor for survival in a multivariate Cox regression analysis. In
      particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01)
      associated with loss of TP53 function. CONCLUSIONS: The results of our study
      indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early
      stage serous ovarian cancer is associated with recurrent disease. Further studies
      related to the findings of chromosomes 17 and 19 are needed to elucidate the
      molecular mechanism behind the recurring genomic aberrations and the poor
      clinical outcome.

PMID- 22967089
TI  - Synthesis of silk fibroin-glycopolypeptide conjugates and their recognition with
      lectin.
AB  - Silk fibroin (SF), the natural fibrous protein created by the  Bombyx mori  silk
      worm, is being increasingly explored as a biomaterial for tissue engineering due
      to its excellent mechanical strength, high oxygen/water permeability, and
      biocompatibility. It is also well known that surface modification of SF with
      organic ligands such as the extracellular protein binding Arg-Gly-Asp (RGD)
      peptides help adhesion and proliferation of cells better-a key requirement for it
      to function as extracellular matrices. In this work, we have conjugated synthetic
      glycopolypeptides (GPs) that were synthesized by controlled ring-opening
      polymerization of alpha-manno-lys N-carboxyanhydrides (NCAs) onto SF by using Cu
      catalyzed click reaction to synthesize a new hybrid material (SF-GP), which we
      believe will have both the mechanical properties of native SF and the molecular
      recognition property of the carbohydrates in the GP. By controlling the amount of
      GP grafted onto SF, we have made three SF-GP conjugates that differ in their
      ability to assemble into films. SF-GP conjugates having a very high content of GP
      formed completely water-soluble brush-like polymer that displayed very high
      affinity toward the lectin concanavalin-A (Con-A). Films cast from SF-GP
      conjugates using lower amounts of grafted GP were more stable in water, and the
      stability can be modulated by varying the amount of GP grafted. The water
      insoluble film SF-GP(25) was also found to bind to fluorescently labeled Con-A,
      as was seen by confocal microscopy. Such SF-GP hybrid films may be useful as
      mimics of extracellular matrices for tissue engineering.

PMID- 22967091
TI  - Ab initio time-domain study of the triplet state in a semiconducting carbon
      nanotube: intersystem crossing, phosphorescence time, and line width.
AB  - Motivated by recent experiments (J. Am. Chem. Soc. 2011, 133, 17156), we used
      nonadiabatic (NA) molecular dynamics implemented within ab initio time-domain
      density functional theory to investigate the evolution of the excited electronic
      singlet and triplet states in the (6,4) carbon nanotube (CNT). The simulation
      simultaneously included the NA electron-phonon interaction and the spin-orbit
      (SO) interaction and focused on the intersystem crossing (ISC) from the first
      excited singlet state (S(1)) to the triplet state (T(1)) and subsequent
      relaxation to the ground electronic state (S(0)). For the first time, the state
      of-the-art methodology (Phys. Rev. Lett. 2005, 95, 163001; Phys. Rev. Lett. 2008,
      100, 197402) has been advanced to include triplet states. The S(1)-T(1) ISC was
      calculated to occur within tens of picoseconds, in agreement with the
      experimental data. This time scale is on the same order as the S(1)-S(0)
      nonradiative decay time obtained previously for the (6,4) CNT. The homogeneous
      phosphorescence line width, which can be measured in single-molecule experiments,
      was predicted to be on the order of 10 meV at room temperature. This value is
      similar to the fluorescence line widths of CNTs suspended in air. The NA electron
      phonon and SO couplings were found to be on the order of 1 meV; however, the
      former fluctuates much more than the latter, causing the ISC rate to be limited
      by the SO interaction rather than NA interaction. The electronic energy lost
      nonradiatively during ISC is deposited into high-frequency optical phonons of the
      CNT arising from C-C stretching motions. The calculations indicate that ISC can
      contribute to the nonradiative energy losses and low photoluminescence quantum
      yields observed in semiconducting CNTs.

PMID- 22967090
TI  - Motivations for active commuting: a qualitative investigation of the period of
      home or work relocation.
AB  - BACKGROUND: Promoting walking or cycling to work (active commuting) could help to
      increase population physical activity levels. According to the habit
      discontinuity and residential self-selection hypotheses, moving home or workplace
      is a period when people (re)assess, and may be more likely to change, their
      travel behavior. Research in this area is dominated by the use of quantitative
      research methods, but qualitative approaches can provide in-depth insight into
      the experiences and processes of travel behavior change. This qualitative study
      aimed to explore experiences and motivations regarding travel behavior around the
      period of relocation, in an effort to understand how active commuting might be
      promoted more effectively. METHODS: Participants were recruited from the
      Commuting and Health in Cambridge study cohort in the UK. Commuters who had moved
      home, workplace or both between 2009 and 2010 were identified, and a purposive
      sample was invited to participate in semi-structured interviews regarding their
      experiences of, and travel behavior before and after, relocating. A grounded
      theory approach was taken to analysis. RESULTS: Twenty-six commuters
      participated. Participants were motivated by convenience, speed, cost and
      reliability when selecting modes of travel for commuting. Physical activity was
      not a primary motivation, but incidental increases in physical activity were
      described and valued in association with active commuting, the use of public
      transport and the use of park-and-ride facilities. CONCLUSIONS: Emphasizing and
      improving the relative convenience, cost, speed and reliability of active
      commuting may be a more promising approach to promoting its uptake than
      emphasizing the health benefits, at least around the time of relocation.
      Providing good quality public transport and free car parking within walking or
      cycling distance of major employment sites may encourage the inclusion of active
      travel in the journey to work, particularly for people who live too far from work
      to walk or cycle the entire journey. Contrary to a straightforward interpretation
      of the self-selection hypothesis, people do not necessarily decide how they
      prefer to travel, relocate, and then travel in their expected way; rather, there
      is constant negotiation, reassessment and adjustment of travel behavior following
      relocation which may offer an extended window of opportunity for travel behavior
      change.

PMID- 22967092
TI  - Evaluation of the effects of 80% methanolic leaf extract of Caylusea abyssinica
      (fresen.) fisch. & Mey. on glucose handling in normal, glucose loaded and
      diabetic rodents.
AB  - BACKGROUND: The leaves of Caylusea abyssinica (fresen.) Fisch. & Mey.
      (Resedaceae), a plant widely distributed in East African countries, have been
      used for management of diabetes mellitus in Ethiopian folklore medicine. However,
      its use has not been scientifically validated. The present study was undertaken
      to investigate antidiabetic effects of the hydroalcoholic leaf extract of C.
      abyssinica extract in rodents. MATERIALS AND METHOD: Male Animals were randomly
      divided into five groups for each diabetic, normoglycemic and oral glucose
      tolerance test (OGTT) studies. Group 1 served as controls and administered 2%
      Tween-80 in distilled water, (TW80); Group 2 received 5 mg/kg glibenclamide
      (GL5); Groups 3, 4 and 5 were given 100 (CA100), 200 (CA200) and 300 (CA300)
      mg/kg, respectively, of the hydroalcoholic extract of C. abyssinica. Blood
      samples were then collected at different time points to determine blood glucose
      levels (BGL). Data were analyzed using one way ANOVA followed by Dunnet's post
      hoc test and p < 0.05was considered as statistically significant. RESULTS: In
      normal mice, CA200 and GL5 induced hypoglycemia starting from the 2nd h but the
      hypoglycemic effect of CA300 was delayed and appeared at the 4th h (p < 0.05 in
      all cases). In diabetic mice, BGL was significantly reduced by CA100 (p < 0.05)
      and CA300 (p < 0.01) starting from the 3rd h, whereas CA200 (p < 0.001) and GL5
      (p < 0.05) attained this effect as early as the 2nd h. In OGTT, TW80 (p < 0.01)
      and CA100 (p < 0.01) brought down BGL significantly at 120 min, while CA200 (p <
      0.001) and GL5 (p < 0.001) achieved this effect at 60 min indicating the oral
      glucose load improving activity of the extract. By contrast, CA300 was observed
      to have no effect on OGTT. Acute toxicity study revealed the safety of the
      extract even at a dose of 2000 mg/kg. Preliminary phytochemical study
      demonstrated the presence of various secondary metabolites, including, among
      others, saponins, flavonoids and alkaloids. CONCLUSION: The results indicate that
      C. abyssinica is endowed with antidiabetic and oral glucose tolerance improving
      actions, particularly at the dose of 200 mg/kg in experimental animals. These
      activities of the plant extract may be related to the presence of secondary
      metabolites implicated in antidiabetic activities of plant extracts via different
      hepatic and extra-hepatic mechanisms. These results thus support the traditional
      use of the leaf extract for the management of diabetes mellitus.

PMID- 22967093
TI  - In situ video-STM studies of methyl thiolate surface dynamics and self-assembly
      on Cu(100) electrodes.
AB  - The atomic-scale surface dynamic behavior of adsorbed methyl thiolate on Cu(100)
      electrodes, prepared via the dissociative adsorption of dimethyl disulfide, was
      studied in 0.01 M HCl solution over a wide regime of coverages. Using video-rate
      in situ STM, we directly observed the motion of the adsorbates within the c(2 *
      2) lattice of the chloride coadsorbates with high spatial and temporal
      resolution, revealing complex mutual interactions of the organic adsorbates as
      well as pronounced interactions with Cu adatoms, which significantly affect the
      thiolate self-assembly. Quantitative measurements of the tracer diffusion of
      isolated thiolates reveal a 35 meV lower diffusion barrier as compared to that of
      sulfide adsorbates with a linear potential dependence of 0.5 eV/V. The effective
      intermolecular interactions between the thiolates resemble those between adsorbed
      sulfide and are repulsive at the nearest-neighbor distance of a(0) within the c(2
      * 2) lattice, attractive at the next-nearest-neighbor distance of ?2a(0) and
      again repulsive at a distance of 2a(0). Thiolates at these small spacings are
      found to exhibit characteristic collective properties, which are significant for
      the self-assembly of these species: First, their mobility is greatly enhanced
      relative to that of isolated thiolates. Second, Cu adatoms can be transiently
      trapped in between the two thiolates of a metastable dimer with an intermolecular
      spacing of ?2a(0). With increasing coverage, small, highly mobile molecular
      clusters and subsequently the formation of ordered adlayer domains with a c(2 *
      6) structure are observed. Common structural elements of the clusters and c(2 *
      6) domains are stripes of thiolate dimers, which are oriented in the [011]
      direction, spaced at distances of ?2a(0) and of which a large fraction is
      occupied by Cu adatoms. The c(2 * 6) phase can be rationalized as a close-packed
      arrangement of these dimer stripes. Because of the self-acceleration of the
      thiolate mobility, the ordering and reorganization of the ordered c(2 * 6)
      adlayers occur orders of magnitude faster than the surface diffusion of isolated
      thiolates, illustrating the importance of collective effects in organic self
      organization.

PMID- 22967094
TI  - Phylogeny of moray eels (Anguilliformes: Muraenidae), with a revised
      classification of true eels (Teleostei: Elopomorpha: Anguilliformes).
AB  - The family Muraenidae is one of the largest and most recognizable eel groups.
      Moray eels are key components of marine ecosystems but their relationships remain
      poorly understood. The phylogenetic relationships of the morays are examined
      herein using mitochondrial 12S and 16S sequence data, totaling 1673 bp for 139
      taxa. The results of our analyses found support for a monophyletic family
      Muraenidae that is part of a monophyletic suborder Muraenoidei, which is revised
      to include the anguilliform families Heterenchelyidae and Myrocongridae, and to
      exclude the family Chlopsidae. The muraenids form two monophyletic subfamilies,
      Muraeninae and Uropterygiinae. Of the genera that had multiple species included
      for analysis, only the type genus of the family, Muraena, is found to be
      monophyletic. In the subfamily Uropterygiinae, Uropterygius is not recovered as a
      monophyletic genus. In the subfamily Muraeninae, the species-rich piscivorous
      genera, Enchelycore and Gymnothorax, and the durophagous genus, Echidna, are
      demonstrably not monophyletic. The monotypic Gymnomuraena is the sister group to
      all other muraenine species. The relationships within Muraenidae require much
      additional study and its genera remain in urgent need of revision. The order
      Anguilliformes is revised herein to include four suborders: Anguilloidei,
      Congroidei, Muraenoidei, and Synaphobranchoidei. All four families of the order
      Saccopharyngiformes are nested within Anguilliformes, recovered as part of a
      clade that includes Anguillidae; the saccopharyngiform families are referred to
      the suborder Anguilloidei sensu novum.

PMID- 22967095
TI  - Integrating risk and resilience approaches to catastrophe management in
      engineering systems.
AB  - Recent natural and man-made catastrophes, such as the Fukushima nuclear power
      plant, flooding caused by Hurricane Katrina, the Deepwater Horizon oil spill, the
      Haiti earthquake, and the mortgage derivatives crisis, have renewed interest in
      the concept of resilience, especially as it relates to complex systems vulnerable
      to multiple or cascading failures. Although the meaning of resilience is
      contested in different contexts, in general resilience is understood to mean the
      capacity to adapt to changing conditions without catastrophic loss of form or
      function. In the context of engineering systems, this has sometimes been
      interpreted as the probability that system conditions might exceed an irrevocable
      tipping point. However, we argue that this approach improperly conflates
      resilience and risk perspectives by expressing resilience exclusively in risk
      terms. In contrast, we describe resilience as an emergent property of what an
      engineering system does, rather than a static property the system has. Therefore,
      resilience cannot be measured at the systems scale solely from examination of
      component parts. Instead, resilience is better understood as the outcome of a
      recursive process that includes: sensing, anticipation, learning, and adaptation.
      In this approach, resilience analysis can be understood as differentiable from,
      but complementary to, risk analysis, with important implications for the adaptive
      management of complex, coupled engineering systems. Management of the 2011
      flooding in the Mississippi River Basin is discussed as an example of the
      successes and challenges of resilience-based management of complex natural
      systems that have been extensively altered by engineered structures.

PMID- 22967096
TI  - Detection of total and A1c-glycosylated hemoglobin in human whole blood using
      sandwich immunoassays on polydimethylsiloxane-based antibody microarrays.
AB  - The percentage of glycosylated hemoglobin A1c (%GHbA1c) in human whole blood
      indicates the average plasma glucose concentration over a prolonged period of
      time and is used to diagnose diabetes. However, detecting GHbA1c in the whole
      blood using immunoassays has limited detection sensitivity due to its low
      percentage in total hemoglobin (tHb) and interference from various glycan
      moieties in the sample. We have developed a sandwich immunoassay using an
      antibody microarray on a polydimethylsiloxane (PDMS) substrate modified with
      fluorinated compounds to detect tHb and glycosylated hemoglobin A1c (GHbA1c) in
      human whole blood without sample pretreatment. A polyclonal antibody against
      hemoglobin (Hb) immobilized on PDMS is used as a common capture probe to enrich
      all forms of Hb followed by detection via monoclonal anti-Hb and specific
      monoclonal anti-GHbA1c antibodies for tHb and GHbA1c detection, respectively.
      This method prevents the use of glycan binding molecules and dramatically reduces
      the background interference, yielding a detection limit of 3.58 ng/mL for tHb and
      0.20 ng/mL for GHbA1c. The fluorinated modification on PDMS is superior to the
      glass substrate and eliminates the need for the blocking step which is required
      in commercial enzyme linked immunosorbent assay (ELISA) kits. Moreover, the
      detection sensitivity for GHbA1c is 4-5 orders of magnitude higher, but the
      required sample amount is 25 times less than the commercial method. On the basis
      of patient sample data, a good linear correlation between %GHbA1c values
      determined by our method and the certified high performance liquid chromatography
      (HPLC) standard method is shown with R(2) > 0.98, indicating the great promise of
      the developed method for clinical applications.

PMID- 22967097
TI  - Chironomid egg masses harbour the clinical species Aeromonas taiwanensis and
      Aeromonas sanarellii.
AB  - Bacteria of the genus Aeromonas are found worldwide in aquatic environments and
      may produce human infections. In 2010, two new clinical species, Aeromonas
      sanarellii and Aeromonas taiwanensis, were described on the basis of one strain
      recovered from wounds of hospitalized patients in Taiwan. So far, only four
      environmental isolates of A. sanarellii and one of A. taiwanensis have been
      recorded from waste water in Portugal and an additional clinical strain of A.
      taiwanensis from the faeces of a patient with diarrhoea in Israel. In the present
      study, strains belonging to these two species were identified from chironomid egg
      masses from the same area in Israel by sequencing the rpoD gene. This represents
      a new environmental habitat for these novel species. The first data on the
      virulence genes and antibiotic susceptibility are provided. The isolates of these
      two new species possess multiple virulence genes and are sensitive to amikacin,
      aztreonam, cefepime, cefoxatime, ceftazidime, ciprofloxacin, gentamicin,
      piperacillin-tazobactam, tigecycline, tobramycin, trimethoprim-sulfamethoxazole
      and imipenem. The key phenotypic tests for the differentiation of these new
      species from their closest relative Aeromonas caviae included the utilization of
      citrate, growth at 45  degrees C in sheep blood agar and acid production of
      cellobiose.

PMID- 22967098
TI  - Does IL28B genotyping still have a role in the era of direct-acting antiviral
      therapy for chronic hepatitis C infection?
AB  - IL28B genotype has been shown to be the strongest pretreatment predictor of
      sustained virological response (SVR) in patients with genotype 1 chronic
      hepatitis C infection (CHC) treated with pegylated interferon (peg-IFN) and
      ribavirin (RBV). Patients carrying the good response genotype have a two- to
      threefold higher chance of SVR than those with a poor response genotype, manifest
      as dramatically improved early viral kinetics. However, the treatment paradigm
      for CHC is changing with the introduction of potent direct-acting antivirals
      (DAAs). IL28B genotype remains relevant to both telaprevir and boceprevir
      treatment regimens, although the strength of association with virological
      response is attenuated. The association between IL28B genotype and outcomes of
      treatment regimens that involve peg-IFN plus combination DAA therapy, or IFN-free
      regimens, is currently being evaluated. IL28B genotype may remain relevant to
      individualizing the choice of treatment regimen in the future.

PMID- 22967099
TI  - Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV
      coinfected patients.
AB  - The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases
      (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV)
      mono or HIV- hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian
      adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68
      were HCV-monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B
      coinfection, non-infective liver diseases or HAART adherence <75% were excluded.
      LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs
      (MMP -1,-2,-3,-8,-9,-10 and -13) and their tissue inhibitors (TIMP-1,-2 and -4)
      were measured by ELISA microarrays. Associations with LF were statistically
      analysed. Protease inhibitors, usually administered to patients with advanced LF
      were excluded from the analysis. Increased LF was significantly associated with
      d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001)
      and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P <
      0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of
      lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir
      (P = 0.02) and current CD4(+) T-cells (P < 0.0001), low gain of CD4(+) T-cells
      after HAART (P = 0.01) and higher MMP-2 (P = 0.02) and TIMP-2 serum levels (P =
      0.02). By logistic regression the only variables significantly associated with
      increased LF were: use of ddI (OR 8.77, 95% CI: 2.36-32.26; P = 0.005), male
      gender (OR 7.75, 95% CI: 2.33-25.64, P = 0.0008), HCV viral load (in log) (OR
      3.53, 95% CI: 2.16-5.77; P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09
      1.34, P = 0.0003). We conclude that only higher HCV viral load, older age, male
      gender, and use of ddI associated independently with increased LF in our study.

PMID- 22967100
TI  - Anti-interferon-alpha neutralizing antibody is associated with nonresponse to
      pegylated interferon-alpha plus ribavirin in chronic hepatitis C.
AB  - Pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV) treatment fails
      to achieve a sustained virological response (SVR) in approximately 20-50% of
      patients with chronic hepatitis C virus (HCV) infection. We assessed the
      contribution of an anti-IFN-alpha neutralizing antibody (NAb) on the nonresponse
      to treatment. NAbs were detected using an antiviral assay that assessed the
      neutralizing effects of serum samples against IFN. Serum samples were obtained at
      the end of the treatment and evaluated for the presence of NAbs using recombinant
      IFN-alpha as a standard. We studied 129 PEG-IFN-alpha/RBV-treated patients. In
      the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who
      did not respond, seven (15%) were positive for NAbs. We also examined an
      additional 83 patients who had not responded to PEG-IFN-alpha treatment, and
      detected 12 with NAbs. Patients with good IFN-responsive characteristics,
      including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were
      included in the 19 patients with NAbs. No NAbs interfered with the antiviral
      activity of natural human IFN-beta (nIFN-beta) and re-treatement of patients with
      NAbs with nIFN-beta/RBV achieved SVR. Our analyses revealed that the emergence of
      anti-IFN-alpha NAbs was a candidate causal factor of PEG-IFN-alpha-treatment
      failure. Therefore, these antibodies should be assayed in patients who do not
      respond to PEG-IFN-alpha therapy, and if detected, other effective treatments,
      i.e., medications that are not neutralized by anti-IFN-alpha NAbs, should be
      considered.

PMID- 22967101
TI  - SCCA-IC serum levels are predictive of clinical response in HCV chronic hepatitis
      to antiviral therapy: a multicentric prospective study.
AB  - The combination of pegylated interferon (Peg-IFN) and ribavirin is currently the
      gold standard therapy in patients with HCV chronic infection. The duration of
      therapy, as well as the therapeutic dosage, depend on the genotype.
      Identification of the genotype and rapid virological response (RVR) are widely
      accepted as the most important predictors of clinical outcome during antiviral
      therapy but to optimize cost-benefits and to reduce possible side effects,
      further prognostic factors are needed. Squamous cell carcinoma antigens
      immunocomplex (SCCA-IC) has been reported to be increased in the serum of
      patients with liver cancer. In this multicentric prospective study, we
      investigated the serum levels of SCCA-IC in 103 patients with HCV chronic
      infection. Serum HCV-RNA was detected before the beginning of treatment, after 4,
      12, 24 or 48 weeks, and at week 24 during follow-up. RVR, early virological
      response and sustained virological response (SVR) were assessed following the
      international guidelines. SCCA-IC levels were higher in responders (238 AU,
      interquartile difference 130-556 AU) and decreased significantly to 125 AU (70
      290 AU). The mean baseline value in nonresponders was 149 AU (86.5-306.5 AU), but
      after 4 weeks of treatment the serum levels decreased to 115 AU (80-280 AU): the
      profile of reduction was different between patients with or without a positive
      SVR. Logistic regression with SVR as dependent variable identified as significant
      independent variables: the reduction in SCCA-IC after 1 month (OR = 4.82; 95% CI
      1.39-16.67; P = 0.131) and a genotype other than 1 (OR = 0.094; 95% CI 0.21-0.42;
      P = 0.002); sex and age were also significant factors influencing SVR. SCCA-IC
      seems to be a reliable independent prognostic marker of therapeutic effectiveness
      in anti-HCV positive patients undergoing antiviral therapy.

PMID- 22967102
TI  - Interobserver discrepancy in liver fibrosis using transient elastography.
AB  - Transient elastography is a useful method to assess liver fibrosis, but
      uncertainties still exist regarding reliability and reproducibility of the
      technique. We aimed to improve knowledge on interobserver variability with the
      procedure and tried to find factors associated with such variability. This was a
      cross-sectional study to compare the results of transient elastography performed
      by two different operators, one test made just after the other. We assessed both
      results with correlation tests and with repeated parametric or nonparametric
      tests, as needed. We also carried out a multivariate analysis to find factors
      associated with discrepancy in the results obtained by the two operators. We
      included a total of 333 pairs of transient elastography tests, belonging to 274
      different patients. A total of 325 pairs of tests (97.6%) were valid. Results of
      the first and the second tests were, respectively, median (and interquartile
      range) of direct measurement 6.2 (4.6-10.6) and 6.0 (4.4-10.1) kPa (P = 0.012),
      and mean +/- standard deviation of log(10) of direct measurement 0.892 +/- 0.316
      and 0.871 +/- 0.324 (P = 0.001). In 87 pairs of tests (26.7%), a discrepancy of
      at least 2 kPa between both results was found, and in 15 pairs of tests (4.6%), a
      discrepancy of at least 10 kPa was found. Discordance of at least one stage
      between both measurements was noted in 74 pairs of tests (22.8%). An association
      was found between higher stiffness and discrepancy between both operators (P <
      0.001). Although transient elastography is a very convenient test to assess liver
      fibrosis in clinical practice, interobserver discrepancy in results is common and
      represents a significant problem with the technique. Discrepant results are more
      common in patients with higher values of stiffness.

PMID- 22967103
TI  - Mutations associated with occult hepatitis B virus infection result in decreased
      surface antigen expression in vitro.
AB  - Occult hepatitis B virus (HBV) infection is characterized by the absence of
      detectable hepatitis B surface antigen (HBsAg) in the serum, despite detectable
      HBV DNA. Investigations of the mechanisms underlying the development of occult
      HBV infection are lacking in the current literature, although viral mutations in
      the surface region, resulting in decreased HBsAg expression or secretion,
      represent one potential mechanism. Wild-type HBsAg expression vectors were
      constructed from genotype-matched chronic HBV sequences. Site-directed
      mutagenesis was then utilized to introduce three genotype A mutations - M103I,
      K122R and G145A - associated with occult HBV infection in vivo, alone and in
      combination, into the wild-type HBsAg vectors. Transfection of Huh7 and HepG2
      cell lines was performed, and cell culture supernatants and cell lysates were
      collected over 7 days to assess the effects of these mutations on extracellular
      and intracellular HBsAg levels. The G145A mutation resulted in significantly
      decreased extracellular and intracellular HBsAg expression in vitro. The most
      pronounced reduction in HBsAg expression was observed when all three mutations
      were present. The mutations evaluated in vitro in the current study resulted in
      decreased HBsAg expression and potentially increased hepatic retention and/or
      decreased hepatic secretion of synthesized HBsAg, which could explain the lack of
      HBsAg detection that is characteristic of occult HBV infection in vivo.

PMID- 22967104
TI  - Prediction of response to entecavir therapy in patients with HBeAg-positive
      chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels.
AB  - Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen
      (HBeAg) assays are emerging as effective tools of on-treatment predictors of
      response to antiviral agents, in addition to monitoring serum HBV DNA levels.
      However, the dynamic relationship between quantitative HBsAg, as well as HBeAg
      and HBV DNA, and the predictability of subsequent clinical outcomes during
      entecavir (ETV) therapy remain unclear. Eighty-two patients with HBeAg-positive
      chronic hepatitis B (CHB) received ETV therapy for >=3 years. Virologic response
      (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among
      baseline and on-treatment factors, on-treatment HBV DNA levels performed better
      with respect to the prediction of response than HBsAg and HBeAg levels.
      Especially, the performance of absolute values of HBV DNA with respect to
      response was superior to HBV DNA decline from the baseline. The best predictive
      value was an absolute HBV DNA level of 2.3 log(10) IU/mL at month 6 (areas under
      the curve [AUROC], 0.977; 95% CI, 0.940-1.000; P < 0.001). HBeAg seroconversion
      after 3 years of therapy was achieved in 26 (31.7%) patients. On-treatment HBeAg
      levels performed better with respect to the prediction of seroconversion than
      HBsAg and HBV DNA levels. The best cut-off value for the HBeAg level at month 12
      for the prediction of seroconversion was 0.62 log(10) PEIU/mL. Although the HBsAg
      level at baseline is often used to predict the antiviral potency of entecavir, on
      treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent
      clinical outcomes in HBeAg-positive CHB patients with entecavir treatment.

PMID- 22967105
TI  - Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in
      treatment-naive patients with HBV-related decompensated cirrhosis.
AB  - Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV)
      infection have a high morbidity/mortality rate, and the treatment remains a
      challenge. We studied the safety and efficacy of telbivudine and lamivudine in
      such patients. This noninferiority, double-blind trial randomized 232 treatment
      naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive
      once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary
      composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL,
      normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score
      improvement/stabilization at week 52. Response rates using a post hoc modified
      endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to
      treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018)
      and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine.
      Telbivudine treatment was an independent predictive factor for HBV DNA <300
      copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined
      composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0%
      (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in
      telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was
      associated with a significant improvement in glomerular filtration rate compared
      to lamivudine treatment and was also associated with a trend for improvement in
      survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine
      compared to lamivudine was associated with a higher rate of patients with both
      viral suppression and ALT normalization, a trend towards a higher rate of
      survival and significant improvement in glomerular filtration.

PMID- 22967106
TI  - Large hepatitis delta antigen activates STAT-3 and NF-kappaB via oxidative
      stress.
AB  - Hepatitis delta virus (HDV) coinfection or superinfection in hepatitis B virus
      (HBV)-infected patients results in a more aggressive liver disease, with more
      often fulminant forms and more rapid progression to cirrhosis and hepatocellular
      carcinoma. The mechanism(s) for this pejorative evolution remains unclear. To
      explore a specific HDV pathogenesis, we used a model of transient transfection of
      plasmids expressing the small (sHDAg or p24) or the large (LHDAg or p27) delta
      antigen in hepatocyte cell lines. We found that the production of reactive oxygen
      species was significantly higher in cells expressing p27. Consequently, p27
      activated the signal transducer and activator of transcription-3 (STAT-3) and the
      nuclear factor kappa B (NF-kappaB) via the oxidative stress pathway. Moreover in
      the presence of antioxidants (PDTC, NAC) or calcium inhibitors (TMB-8, BAPTA-AM,
      Ruthenium Red), p27-induced activation of STAT-3 and NF-kappaB was dramatically
      reduced. Similarly, using a mutated form of p27, where the cysteine 211
      isoprenylation residue was replaced by a serine, a significant reduction of STAT
      3 and NF-kappaB activation was seen, suggesting the involvement of isoprenylation
      in this process. Additionally, we show that p27 is able to induce oxidative
      stress through activation of NADPH oxidase-4. These results provide insight into
      the mechanisms by which p27 can alter intracellular events relevant to HDV
      related liver pathogenesis.

PMID- 22967107
TI  - Specific primer sets used to amplify by PCR the hepatitis B virus overlapping
      S/Pol region select different viral variants.
AB  - PCR detection of viral genomes has provided new insights into viral diagnosis.
      Nowadays, it is the most frequently used nucleic acid testing (qualitative and
      quantitative) technique. The aim of this study was to analyse the major
      circulating hepatitis B virus (HBV) variants PCR-amplified by three sets of
      primers in a patient infected with genotype E. The HBV S/Pol overlapping genomic
      region was amplified from the serum of an infected child using three primer sets
      previously described. Sequence analysis corresponding to the HBV S/Pol region
      revealed the presence of different viral populations depending on the set of
      primers used. D144A S-escape mutant was detected with two of the primer sets,
      while the rtL217R mutant within the Pol - conferring resistance to Adefovir -
      could be picked up with a different pair of primer sets. This study undoubtedly
      implies that the description of viral polymorphisms should be stated together
      with the sequence of the primers used for PCR amplification when studies of
      escape and/or antiviral-resistant HBV mutants are carried out.

PMID- 22967108
TI  - Phosphatidylinositol 3-kinase is an upstream regulator of the phosphodiesterase
      3B pathway of leptin signalling that may not involve activation of Akt in the rat
      hypothalamus.
AB  - Leptin, the product of the obese gene, regulates energy homeostasis by acting
      primarily at the level of the hypothalamus. Leptin action through its receptor
      involves various pathways, including the signal transducer and activator of
      transcription (STAT)3, phosphatidylinositol 3-kinase (PI3K), and
      phosphodiesterase 3B (PDE3B)-cAMP signalling in the central nervous system and
      peripheral tissues. In the hypothalamus, leptin stimulates STAT3 activation, and
      induces PI3K and PDE3B activities, among others. We have previously demonstrated
      that PDE3B activation in the hypothalamus is critical for transducing the
      anorectic and body weight reducing effects of leptin. Similarly, PI3K has been
      implicated to play a critical role in leptin signalling in the hypothalamus.
      Although, in the insulin signalling pathway, PI3K is known to be an upstream
      regulator of PDE3B in non-neuronal tissues, it is still unknown whether this is
      also the case for leptin signalling in the hypothalamus. To address this
      possibility, the effect of wortmannin, a specific PI3K inhibitor, was examined on
      leptin-induced PDE3B activity in the hypothalamus of male rats.
      Intracerebroventricular injection of leptin (4 MUg) significantly increased PDE3B
      activity by two-fold in the hypothalamus as expected. However, previous
      administration of wortmannin completely reversed the stimulatory effect of leptin
      on PDE3B activity in the hypothalamus. To investigate whether leptin stimulates
      phospho (p)-Akt levels and that there might be a possible upstream regulator of
      PDE3B, we examined the effects of i.c.v. leptin on p-Akt levels in the
      hypothalamus and compared them with the known stimulatory effect of insulin on p
      Akt. We observed that insulin increased p-Akt levels but leptin failed to do so,
      although it increased p-STAT3 levels, in the rat hypothalamus.
      Immunocytochemistry confirmed the biochemical findings in that leptin failed but
      insulin increased the number of p-Akt positive cells in various hypothalamic
      nuclei. Taken together, these results implicate PI3K but not Akt as an upstream
      regulator of the PDE3B pathway of leptin signalling in the rat hypothalamus.

PMID- 22967109
TI  - Translational immunologic safety evaluation: a perspective.
AB  - Although translational research is a rapidly evolving area of biomedical
      sciences, translational immunologic safety evaluation has so far attracted only
      very limited attention. Assays and animal models have been developed to identify
      immunotoxic hazards related to immunosuppression, but less attention has been
      paid to immunostimulation, hypersensitivity, and autoimmunity. Some of these
      assays and models are recommended by regulatory bodies, even though it is as yet
      unsure to what extent they can predict the potential of, or lack of, new chemical
      entities and drug candidates for inducing significant immunotoxic effects. A
      translational approach should attempt to standardize and validate those models,
      assays, and biomarkers that could be used in regulatory non-clinical safety
      studies as well as clinical studies. Beyond translational immunologic safety,
      immune monitoring during clinical studies is intended to identify and evaluate
      potential immune safety issues not seen in non-clinical studies. Based on this
      overview of the current knowledge, it can be concluded that much remains to be
      done to conduct translational studies helpful to enhance the immunologic safety
      of drugs and chemicals.

PMID- 22967110
TI  - Long-term outcome following pregnancy in women with a systemic right ventricle:
      is the deterioration due to pregnancy or a consequence of time?
AB  - INTRODUCTION: The right ventricle (RV) supports the systemic circulation in
      patients who have had an intraatrial repair of transposition of the great
      arteries or have congenitally corrected transposition. There is concern about the
      ability of a systemic RV to support the additional volume load of pregnancy, and
      previous studies have reported deterioration in RV function following pregnancy.
      However, conditions with a systemic RV are also associated with progressive RV
      dysfunction over time. To date, no study has examined whether the deterioration
      associated with pregnancy is due to the physiological changes of pregnancy
      itself, or is part of the known deterioration that occurs with time in these
      patients. METHODS: Women who had undergone pregnancy under the care of the Adult
      Congenital Heart Disease Unit at the Queen Elizabeth Hospital were
      retrospectively identified and matched to separate male and nulliparous female
      controls. Functional status (New York Health Association [NYHA]), RV function,
      and systemic atrioventricular valve regurgitation were recorded for each group at
      baseline, postpregnancy (or at 1 year for control groups) and at latest follow
      up. RESULTS: Eighteen women had 31 pregnancies (range 1-4) resulting in 32 live
      births. There were no maternal but one neonatal death. At baseline, there was no
      significant difference in NYHA class or RV function between pregnancy and control
      groups. In postpregnancy, there was a significant deterioration in the pregnant
      group alone for both NYHA class (P = 0.004) and RV function (P = 0.02). At latest
      follow-up, there was a significant deterioration in RV function in all three
      groups. There was still a reduction from baseline in NYHA of women who had
      undergone pregnancy (P = 0.014), which again was not seen in the controls groups.
      CONCLUSION: This study suggests that pregnancy is associated with a premature
      deterioration in RV function in women with a systemic RV. These women are also
      more symptomatic, with a greater reduction in functional class compared with
      patients with a systemic RV who do not undergo pregnancy. This study will allow
      this cohort of women to be more accurately counseled as to the potential long
      term risks of pregnancy.

PMID- 22967111
TI  - SNP-array reveals genome-wide patterns of geographical and potential adaptive
      divergence across the natural range of Atlantic salmon (Salmo salar).
AB  - Atlantic salmon (Salmo salar) is one of the most extensively studied fish species
      in the world due to its significance in aquaculture, fisheries and ongoing
      conservation efforts to protect declining populations. Yet, limited genomic
      resources have hampered our understanding of genetic architecture in the species
      and the genetic basis of adaptation to the wide range of natural and artificial
      environments it occupies. In this study, we describe the development of a medium
      density Atlantic salmon single nucleotide polymorphism (SNP) array based on
      expressed sequence tags (ESTs) and genomic sequencing. The array was used in the
      most extensive assessment of population genetic structure performed to date in
      this species. A total of 6176 informative SNPs were successfully genotyped in 38
      anadromous and freshwater wild populations distributed across the species natural
      range. Principal component analysis clearly differentiated European and North
      American populations, and within Europe, three major regional genetic groups were
      identified for the first time in a single analysis. We assessed the potential for
      the array to disentangle neutral and putative adaptive divergence of SNP allele
      frequencies across populations and among regional groups. In Europe, secondary
      contact zones were identified between major clusters where endogenous and
      exogenous barriers could be associated, rendering the interpretation of
      environmental influence on potentially adaptive divergence equivocal. A small
      number of markers highly divergent in allele frequencies (outliers) were observed
      between (multiple) freshwater and anadromous populations, between northern and
      southern latitudes, and when comparing Baltic populations to all others. We also
      discuss the potential future applications of the SNP array for conservation,
      management and aquaculture.

PMID- 22967112
TI  - Efficient multicomponent strategy to pentacyclic pyrazole-fused naphtho[1,8
      fg]isoquinolines through cleavage of two carbon-carbon bonds.
AB  - Multicomponent reactions of acenaphthylene-1,2-dione with diaroylmethanes and
      electron-rich pyrazol-5-amines have been discovered. A series of new and
      polyfunctionalized pentacyclic pyrazole-fused naphtho[1,8-fg]isoquinolines were
      regioselectively synthesized. The reactions were easy to perform simply by mixing
      three common reactants in AcOH. During these reaction processes, the insertion of
      active methylene of diaroylmethane into the sp(2)-sp(2) C-C bond of the cyclohexa
      2,5-dienone ring was readily achieved and two C-C bonds were cleaved under
      transition-metal-free conditions.

PMID- 22967113
TI  - Distribution and variability study of the femur cortical thickness from computer
      tomography.
AB  - In the context of patient-specific 3D bone reconstruction, enhancing the surface
      with cortical thickness (COT) opens a large field of applications for research
      and medicine. This functionality calls for database analysis for better knowledge
      of COT. Our study provides a new approach to reconstruct 3D internal and external
      cortical surfaces from computer tomography (CT) scans and analyses COT
      distribution and variability on a set of asymptomatic femurs. The reconstruction
      method relies on a short (~5 min) initialisation phase based on 3D reconstruction
      from biplanar CT-based virtual X-rays and an automatic optimisation phase based
      on intensity-based cortical structure detection in the CT volume, the COT being
      the distance between internal and external cortical surfaces. Surfaces and COT
      show root mean square reconstruction errors below 1 and 1.3 mm. Descriptions of
      the COT distributions by anatomical regions are provided and principal component
      analysis has been applied. The first mode, 16-50% of the variance, corresponds to
      the variation of the mean COT around its averaged shape; the second mode, 9-28%,
      corresponds to a fine variation of its shape. A femur COT model can, therefore,
      be described as the averaged COT distribution in which the first parameter
      adjusts its mean value and a second parameter adjusts its shape. 

PMID- 22967114
TI  - The neurophysiologist, the neurosurgeon and the trigeminal thermorhizotomy.

PMID- 22967115
TI  - Specific detection of cultivable Helicobacter pylori cells from wastewater
      treatment plants.
AB  - BACKGROUND: Helicobacter pylori is present in surface water and wastewater, and
      biofilms in drinking water systems have been reported as possible reservoirs of
      H. pylori. However, its ability to survive in an infectious state in the
      environment is hindered because it rapidly loses its cultivability. The aim of
      this study was to determine the presence of cultivable and therefore viable H.
      pylori in wastewater treatment plants to understand the role of wastewater in the
      pathogen's transmission. MATERIALS AND METHODS: A modified filter technique was
      used to obtain a positive H. pylori culture, and specific detection of this
      pathogen was achieved with FISH and PCR techniques. RESULTS: A total of six
      positive H. pylori cultures were obtained from the water samples, and molecular
      techniques positively identified H. pylori in 21 culture-negative samples.
      CONCLUSIONS: The combination of a culturing procedure after sample filtration
      followed by the application of a molecular method, such as PCR or FISH, provides
      a specific tool for the detection, identification, and direct visualization of
      cultivable and therefore viable H. pylori cells from complex mixed communities
      such as water samples.

PMID- 22967116
TI  - Influence of Helicobacter pylori infection on gastric acid secretion in pre
      school Bangladeshi children.
AB  - BACKGROUND: The effect of Helicobacter pylori (H. pylori) infection on gastric
      acid secretion (GAS) is poorly defined in children. OBJECTIVE: To determine
      whether H. pylori infection is associated with abnormal GAS in children. METHODS:
      We studied 30 H. pylori-infected children (identified by a positive urea breath
      test) and 30 noninfected children of both sexes, aged 2-5 years. Gastric pH and
      GAS were measured before and 8 weeks after the completion of a 2-week course of
      anti- H. pylori therapy (omeprazole, clarithromycin, and amoxicillin). Gastric
      acid output (GAO) was quantified during a 1-h basal period (GAO-B) (mmol/h) and a
      1-hour stimulated period (GAO-S) (mmol/hour) following subcutaneous
      administration of pentagastrin (6 MUg/kg). RESULTS: A significantly greater
      number of infected children had a high gastric pH (>4.0, p = 0.03) compared with
      the noninfected group. GAO-B and GAO-S in H. pylori-infected children were
      significantly lower, around 50%, compared with children without H. pylori
      infection. H. pylori-eradication therapy resulted in a rise of both the mean GAO
      B (paired t-test before vs. after therapy; 0.28 +/- 0.40 vs. 0.62 +/- 1.0, p =
      0.12) and GAO-S (before vs. after therapy; 2.0 +/- 1.4 vs. 3.4 +/- 2.5, p =
      0.001), with values reaching equivalence to those in the H. pylori-negative
      children (0.71 +/- 0.56 for BAO, 3.3 +/- 2.0 for SAO, p = NS). CONCLUSION: The
      results suggest that the gastric barrier is compromised in children with H.
      pylori infection in Bangladesh. Improvement of GAO following anti- H. pylori
      therapy suggests a causal link between H. pylori infection and depressed GAO in
      this population.

PMID- 22967117
TI  - Association of Malaysian Helicobacter pylori virulence polymorphisms with
      severity of gastritis and patients' ethnicity.
AB  - BACKGROUND AND AIM: Polymorphisms of Helicobacter pylori cagA and vacA genes do
      exist and may contribute to differences in H. pylori infection and gastroduodenal
      diseases among races in the Malaysian population. This study was conducted to
      characterize the polymorphisms in H. pylori cagA and vacA in Malaysian
      population. METHODS: A total of 110 H. pylori isolates were genotyped by PCR and
      sequenced for cagA and PCR-RFLP for vacA. RESULTS: East Asian cagA was
      predominantly detected (64.5%), whereas vacA s1m1 and s1m2 alleles were detected
      in 60.9 and 37.3% of strains, respectively. A statistical association between
      cagA type with patients' ethnicity (p < .0001) and age group >50 years old (p =
      .027) was identified. vacA alleles showed significant association with age group
      >50 years old (p = .017) and increased neutrophil activity in gastric mucosa (p =
      .028 and p = .016 for moderate and marked activity, respectively). Further
      identification of vacA polymorphism revealed that 84% of strains from Malays and
      Indians showed one RFLP pattern (RFLP-1), whereas more than one RFLP patterns
      (RFLP-2, 3, 4, 5, 6, and 8) were predominantly observed in strains from Chinese
      (82%) (p < .0001). Increasing severity of gastric inflammation was observed in
      gastric mucosa infected with strains carrying RFLP-2, 3, 4, 5, and 6 (p = .037).
      About 86.6% of H. pylori strains with East Asian cagA were vacA RFLP-2, 3, 4, 5,
      6, and 8, and 88% of Western cagA strains were vacA RFLP-1 (p < .0001). Chinese
      and Indians are susceptible to different virulence genotypes of H. pylori,
      whereas Malays showed a mixed virulence genotypes. CONCLUSION: Marked differences
      in the polymorphisms of cagA and vacA were observed among strains in Malaysian
      population. This provides a new insight into the pathogenicity of H. pylori in
      multiracial population.

PMID- 22967118
TI  - A potential association between Helicobacter pylori CagA EPIYA and
      multimerization motifs with cytokeratin 18 cleavage rate during early apoptosis.
AB  - BACKGROUND AND AIMS: Helicobacter pylori is a highly diverse pathogen, which
      encounters epithelial cells as the initial defense barrier during its lifelong
      infection. The structure of epithelial cells can be disrupted through cleavage of
      microfilaments. Cytokeratin 18 (CK18) is an intermediate filament, the cleavage
      of which is considered an early event during apoptosis following activation of
      effector caspases. METHODS: Helicobacter pylori strains were isolated from 76
      dyspeptic patients. cagA 3' variable region and CagA protein status were analyzed
      by PCR and western blotting, respectively. Eight hours post-co-culture of AGS
      cells with different H. pylori strains, flow cytometric analysis was performed
      using M30 monoclonal antibody specific to CK18 cleavage-induced neo-epitope.
      RESULTS: Higher rates of CK18 cleavage were detected during co-culture of AGS
      cells with H. pylori strains bearing greater numbers of cagA EPIYA-C and
      multimerization (CM) motifs. On the other hand, H. pylori strains with greater
      numbers of EPIYA-B relative to EPIYA-C demonstrated a decrease in CK18 cleavage
      rate. Thus, H. pylori-mediated cleavage of CK18 appeared proportional to the
      number of CagA EPIYA-C and CM motifs, which seemed to be downplayed in the
      presence of EPIYA-B motifs. CONCLUSIONS: Our observation associating the
      heterogeneity of cagA variants with the potential of H. pylori strains in the
      induction of CK18 cleavage as an early indication of apoptosis in gastric
      epithelial cells supports the fact that apoptosis may be a type-specific trait.
      However, additional cagA-targeted experiments are required to clearly identify
      the role of EPIYA and CM motifs in apoptosis and/or the responsible effector
      molecules.

PMID- 22967119
TI  - Prevalence and clinicopathologic characteristics of gastric cardia cancer in
      South Korea.
AB  - BACKGROUND AND AIM: Western reports have suggested that the prevalence of gastric
      cardia cancer (GCC) has been increasing, and indicated some differences between
      GCC and gastric noncardia cancer (GNCC). However, few studies have been conducted
      in Asia. The aims of this study were to estimate the prevalence of GCC and to
      evaluate differences of clinicopathologic characteristics between GCC and GNCC in
      South Korea. METHODS: This study was single-center case-control study. A total of
      829 patients with gastric cancer and 270 controls were enrolled between 2003 and
      2011. Baseline characteristics, Helicobacter pylori (H. pylori) infection status,
      and histologic characteristics were compared among three groups (GCC, GNCC, and
      control). RESULTS: Sixty cases (7.2%) of gastric cancer were located in cardia.
      Multivariate analysis showed that male odds ratio (OR, 5.72; 95% CI, 1.72-19.07;
      p = .005) and cigarette smoking (OR, 5.38; 95% CI, 1.39-20.90; p = .015) were
      risk factors of GCC in comparison with control group, but H. pylori infection
      rate was not significant. In the case of GNCC, cigarette smoking (OR, 3.87; 95%
      CI, 1.81-8.29; p < .001), past alcohol intake (OR, 2.82; 95% CI, 1.28-6.20; p =
      .010), intestinal metaplasia (OR, 3.22; 95% CI, 2.00-5.17; p < .001), and H.
      pylori infection (OR, 3.06; 95% CI, 1.90-4.93; p < .001) were risk factors of
      GNCC. Gastroesophageal reflux disease symptoms were higher in the GNCC (21.2%)
      than control group (13.5%) (p = .008). However, in the case of GCC, they were
      similar between the GCC (12.7%) and control group (p = .872). According to
      multivariate analysis, history of H. pylori eradication (OR, 0.34; 95% CI, 0.19
      0.61; p < .001) was associated with a protective effect on GNCC. GCC showed
      higher depth of invasion (p = .038) and frequent distant metastasis (p = .012)
      than GNCC. CONCLUSION: In this referral center based study, the prevalence of GCC
      was 7.2% in South Korea. Risk factors and clinicopathologic characteristics for
      GCC and GNCC were different, supporting that the pathophysiology is different in
      the development of GCC and GNCC.

PMID- 22967120
TI  - Gastrointestinal symptoms and Helicobacter pylori infection in school-age
      children residing in Porto Torres, Sardinia, Italy.
AB  - BACKGROUND: Helicobacter pylori infection is typically acquired in childhood, and
      following the acute event, it is thought that most infections remain
      asymptomatic. H. pylori has been suggested to protect against diarrhea in
      childhood. AIM: To examine the role of H. pylori in gastrointestinal symptoms in
      children. MATERIALS AND METHODS: A cross-sectional sero-epidemiologic study was
      conducted in Porto Torres, Sardinia, Italy. Demographic information,
      socioeconomic factors, and the frequency of upper gastrointestinal symptoms
      during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn,
      halitosis, slow digestion, belching, and weight loss) were evaluated by a
      questionnaire. H. pylori status was determined by ELISA. RESULTS: Approximately
      95% (N = 1741) of school children between the age of 6 and 15 years from Porto
      Torres participated. The sero-prevalence of H. pylori infection was 13.3%
      (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting
      (odds ratio (OR) = 2.2 (95% CI = 1.2-5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3
      2.8)) were each significantly associated with H. pylori infection, and these
      associations remained significant after controlling for other study variables.
      There was no significant association between H. pylori and abdominal pain or
      heartburn (p > .25). CONCLUSIONS: The study does not support either a role of H.
      pylori infection in abdominal pain in children or a protective role against
      diarrheal illnesses or nausea/vomiting.

PMID- 22967121
TI  - The efficacy of second-line anti-Helicobacter pylori therapy using an extended 14
      day levofloxacin/amoxicillin/proton-pump inhibitor treatment--a pilot study.
AB  - BACKGROUND: Large meta-analyses of second-line Helicobacter pylori eradication
      with fluoroquinolone triple therapy have shown that neither 7-day nor 10-day
      therapy provides 90% or better treatment success. Reports describing second-line
      H. pylori eradication using 14-day fluoroquinolone-containing triple therapy are
      few. Current study aimed to determine the efficacy of a 14-day
      levofloxacin/amoxicillin/proton-pump inhibitor regimen as second-line therapy and
      the clinical factors influencing the outcome. MATERIALS AND METHODS: One-hundred
      and one patients who failed H. pylori eradication using the standard triple
      therapy for 7 days were randomly assigned to either a
      levofloxacin/amoxicillin/esomeprazole group (levofloxacin 500 mg once daily,
      amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 14 days) or a
      esomeprazole/metronidazole/bismuth salt/tetracycline group (esomeprazole 40 mg
      twice daily, metronidazole 250 mg four times daily, tripotassium dicitrate
      bismuthate 300 mg four times daily, and tetracycline 500 mg four times daily for
      14 days). Follow-up to assess treatment response consisted of either endoscopy or
      a urea breath test, which were carried out 8 weeks later. RESULTS: Eradication
      rates attained by levofloxacin/amoxicillin/esomeprazole and
      esomeprazole/metronidazole/bismuth salt/tetracycline treatments in the per
      protocol analysis were 44/47 (93.6%; 95% CI = 86-99.8) and 43/47 (91.8%; 95% CI =
      83.2-98.5). In the intention-to-treat analysis, these were 43/47 (86.3%; 95% CI =
      76.5-96.1) in the LAE group (four lost to follow-up) and 43/50 (86%; 95% CI = 76
      96) in the EMBT groups. The observed adverse events were 25.5% and 38.5% among
      the two groups. There was 100% drug compliance among the
      levofloxacin/amoxicillin/esomeprazole group. Levofloxacin-resistant strains
      occurred at a frequency of 32.3%. H. pylori eradication rates for the
      levofloxacin-susceptible strains and levofloxacin-resistant strains were 92%
      (11/12) and 33% (1/3) in the per-protocol analysis. CONCLUSIONS: A 14-day
      levofloxacin/amoxicillin/esomeprazole triple therapy approach provides a >90% per
      protocol report card with the caveat that this approach is markedly less
      effective in the presence of fluoroquinolone resistance. Levofloxacin-resistant
      strains are increasing in Taiwan.

PMID- 22967122
TI  - Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori
      therapy: a pilot study in US Hispanics.
AB  - BACKGROUND: A combination capsule of bismuth, metronidazole, and tetracycline
      plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in
      per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole
      resistant Helicobacter pylori. This study aimed to explore whether extending the
      duration to 14 days would improve overall effectiveness per protocol to >=95%
      (Grade A) in a population in which metronidazole resistance was anticipated to
      exist. METHODS: A one-arm, open-label pilot study of H. pylori-infected,
      asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas,
      received a 14-day course of omeprazole, plus the combination capsule. We cultured
      and Gram-stained specimens obtained using a minimally invasive orogastric brush.
      Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more
      weeks post-therapy. RESULTS: Forty-seven subjects (7 men and 40 women, average
      age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95%
      mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated.
      Side effects were mild and self-limited but contributed to nonadherence. Therapy
      taken for <10 days was more likely to result in eradication failure (p < .001).
      Office-based orogastric brushing was well tolerated; positive cultures were
      obtained in 95%. Gram staining showed H. pylori-like forms in all specimens.
      CONCLUSIONS: This pilot study supports the concept that 14-day OBMT therapy is
      likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than
      a 10-day course where metronidazole resistance is suspected. If confirmed, 14
      days should be recommended in populations where metronidazole resistance is
      common.

PMID- 22967123
TI  - Helicobacter pylori breath testing in an open access system has a high rate of
      potentially false negative results due to protocol violations.
AB  - BACKGROUND: Among available tests to detect Helicobacter pylori (H. pylori), urea
      breath test (UBT) is the most accurate when performed correctly in research
      protocols with unknown validity in clinic settings. MATERIAL AND METHODS: A total
      of 595 subjects at a gastroenterology clinic were tested 620 times with UBT.
      Detailed information about three known factors (recent proton-pump inhibitors
      (PPI), antibiotics, or bismuth, H. pylori eradication treatment finished <4 weeks
      ago, and gastric resection) to make UBT unreliable were prospectively recorded
      before each test. RESULTS: Twenty-three percent (120 of 526) of all negative
      tests fell in one or more of the three categories, which had the potential to
      make UBT unreliable. Of those carried out on persons without being treated
      before, the potential false negative rate was 15%. Among those with previous
      eradication treatment, the rate was around 45%. CONCLUSIONS: If a negative UBT
      could be false negative in up to 23% of cases, then it has a serious lack of
      negative predictive value. A negative UBT should be considered false negative
      until potential protocol violations are excluded.

PMID- 22967124
TI  - Observation of gastric mucosa in Bangladesh, the country with the lowest
      incidence of gastric cancer, and Japan, the country with the highest incidence.
AB  - BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection is high,
      but the incidence of gastric cancer is low in natives of Bangladesh. The gastric
      mucosa was observed in Bangladeshi patients to investigate the differences
      between Bangladeshis and Japanese. MATERIALS AND METHODS: The study involved 418
      Bangladeshi and 2356 Japanese patients with abdominal complaints who underwent
      endoscopy examinations and had no history of H. pylori eradication. The
      prevalence of H. pylori infection and the gastric mucosa in H. pylori-positive
      patients were compared between age-, gender-, and endoscopic diagnosis-matched
      Bangladeshi and Japanese subjects. RESULTS: The prevalence of H. pylori infection
      was higher in Bangladeshi than in Japanese subjects (60.2 and 45.1%,
      respectively). All the scores for chronic inflammation, neutrophil activity,
      glandular atrophy, and intestinal metaplasia were significantly lower in H.
      pylori-positive Bangladeshis than in H. pylori-positive Japanese. The ratio of
      the corpus gastritis score (C) to the antrum gastritis score (A) (C/A ratio) was
      <1 (antrum-predominant gastritis) in all age groups of Bangladeshi subjects,
      whereas the C/A ratio changed from <1 to more than 1 (corpus-predominant
      gastritis) with aging in Japanese subjects. CONCLUSIONS: The scores for glandular
      atrophy and intestinal metaplasia in H. pylori-positive Bangladeshis were
      significantly lower than those in Japanese. All age groups of Bangladeshis had
      antrum-predominant gastritis, whereas corpus-predominant gastritis was more
      common than antrum-predominant gastritis in older Japanese age groups. These
      results may explain the low incidence of gastric cancer in Bangladeshis and the
      high incidence in Japanese.

PMID- 22967125
TI  - Helicobacter pylori infection might contribute to esophageal adenocarcinoma
      progress in subpopulations with gastroesophageal reflux disease and Barrett's
      esophagus.

PMID- 22967127
TI  - Linking on-state memory and distributed kinetics in single nanocrystal blinking.
AB  - Memory effects in single nanocrystal fluorescence blinking are investigated as a
      function of the on-state kinetics for CdSe/ZnS quantum dots and CdSe nanorods.
      The on-state duration probability distributions for single nanocrystal blinking
      traces are characterized by an inverse power law, which crosses over to
      exponential decay for long on-state durations. The correlations of subsequent on
      state durations (Rlog,on) are found to decrease for nanocrystals that display
      earlier crossover times and smaller power law coefficients. Specifically, Rlog,on
      increases from 0.14 +/- 0.02 to a saturation value of 0.44 +/- 0.01 for
      nanocrystals with average crossover times of ~100 ms to more than 5.0 s,
      respectively. The results represent the first link between memory effects and
      blinking kinetics and are interpreted in the framework of two competing charge
      trapping mechanisms. A slow fluctuation-based trapping mechanism leads to power
      law-distributed on durations and significant memory effects; however, the
      additional contribution of an ionization-induced trapping pathway is found to
      induce crossover to exponential decay and decreased memory. Monte Carlo
      simulations of nanocrystal blinking based on the two trapping mechanisms
      reproduce the experimental results, suggesting that the power law component and
      the memory effects correlate with a fluctuation-based mechanism. This effect is
      found to be universal, occurring for two nanocrystal morphologies and in blinking
      data measured using a wide range of continuous and pulsed excitation conditions.

PMID- 22967128
TI  - Innate immune genes including a mucin-like gene, mul-1, induced by ionizing
      radiation in Caenorhabditis elegans.
AB  - The effect of radiation on the intestine has been studied for more than one
      hundred years. It remains unclear, however, whether this organ uses specific
      defensive mechanisms against ionizing radiation. The infection with  Pseudomonas
      aeruginosa  (PA14) in  Caenorhabditis elegans  induces up-regulation of innate
      immune response genes. Here, we found that exposure to ionizing radiation also
      induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec
      4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with
      ionizing radiation before seeding on PA14 lawn plate significantly increased
      survival rate in the nematode. We also studied transcription pathway of the mul-1
      in response to ionizing radiation. Induction of mul-1 gene was highly dependent
      on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1
      signal pathway works to enhance induction of this gene. The mul-1 gene showed a
      different induction pattern from the DNA damage response gene, ced-13, which
      implies that the expression of this gene might be triggered as an indirect effect
      of radiation. Silencing of the mul-1 gene led to growth retardation after
      treatment with ionizing radiation. We describe the cross-tolerance between the
      response to radiation exposure and the innate immune system.

PMID- 22967130
TI  - Survey of soy protein flour as a novel dry strength agent for papermaking
      furnishes.
AB  - A series of experiments were conducted on recycled pulp samples for the novel
      purpose of determining the efficacy of employing soy protein flour to increase
      the strength of dry paper. Values of short span compression and tensile strength
      were the prime criteria for comparison based on industrial considerations.
      Various conditions were considered to uncover effective schemes for applying the
      soy proteins under industrial-like papermaking conditions including alkaline
      versus acidic as well as high or low ionic content papermaking conditions. A
      hybrid system of starch, a dry strength additive currently used in paper
      furnishes, and soy protein was considered to study the possible existence of any
      synergistic chemical effects. Results indicated that a 1 part (by mass) soy
      protein to 3 parts cationic starch hybrid system resulted in the highest strength
      increase in comparison to solely either the soy protein or the cationic starch as
      dry strength additives.

PMID- 22967129
TI  - Modeling coding-sequence evolution within the context of residue solvent
      accessibility.
AB  - BACKGROUND: Protein structure mediates site-specific patterns of sequence
      divergence. In particular, residues in the core of a protein (solvent
      inaccessible residues) tend to be more evolutionarily conserved than residues on
      the surface (solvent-accessible residues). RESULTS: Here, we present a model of
      sequence evolution that explicitly accounts for the relative solvent
      accessibility of each residue in a protein. Our model is a variant of the Goldman
      Yang 1994 (GY94) model in which all model parameters can be functions of the
      relative solvent accessibility (RSA) of a residue. We apply this model to a data
      set comprised of nearly 600 yeast genes, and find that an evolutionary-rate ratio
      omega that varies linearly with RSA provides a better model fit than an RSA
      independent omega or an omega that is estimated separately in individual RSA
      bins. We further show that the branch length t and the transition-transverion
      ratio kappa also vary with RSA. The RSA-dependent GY94 model performs better than
      an RSA-dependent Muse-Gaut 1994 (MG94) model in which the synonymous and non
      synonymous rates individually are linear functions of RSA. Finally, protein core
      size affects the slope of the linear relationship between omega and RSA, and gene
      expression level affects both the intercept and the slope. CONCLUSIONS: Structure
      aware models of sequence evolution provide a significantly better fit than
      traditional models that neglect structure. The linear relationship between omega
      and RSA implies that genes are better characterized by their omega slope and
      intercept than by just their mean omega.

PMID- 22967131
TI  - Peri-implantitis versus periodontitis: functional differences indicated by
      transcriptome profiling.
AB  - BACKGROUND: Periodontitis and Periimplantitis are oftentimes discussed as one
      entity, which is reflected by therapeutical as well as by scientific approaches.
      It is unclear, to which extent the similarity of the clinical characteristics is
      attributed to similarities in the underlying disease mechanisms. PURPOSE: The
      main objective of the study is to display if or how different periimplantitis and
      periodontitis are on the mRNA level, representing a high-resolution map of
      disease-associated events. MATERIALS AND METHODS: Aiming to describe the
      pathophysiological mechanisms in vivo, primary gingival tissue from 7
      periimplantitis patients, 7 periodontitis patients and 8 healthy controls was
      employed in order to generate genome wide transcriptome profiles. RESULTS: On the
      basis of quantitative transcriptome analysis, we could show that periimplantitis
      and periodontitis exhibit significantly different mRNA signatures. Additionally
      we present a disease associated mRNA profile, which displays potential
      periimplantitis disease mechanisms. A gene ontology analysis revealed various
      pathways, supporting the hypothesis of periimplantitis being a complex
      inflammatory disorder with a unique pathophysiology. While in periimplantitis
      tissue the regulation of transcripts related to innate immune responses and
      defense responses were dominating, in periodontitis tissues bacterial response
      systems prevailed. CONCLUSIONS: Taken together, our results suggest considering
      periimplantitis and periodontitis as disease entities with shared as well as with
      distinct features, which should be reflected on the therapeutical as well as on
      the scientific level.

PMID- 22967132
TI  - Role of heat shock protein 47 in transdifferentiation of human tenon's
      fibroblasts to myofibroblasts.
AB  - BACKGROUND: Heat shock protein 47 (Hsp47) is a well-known molecular chaperone in
      collagen synthesis and maturation. The aim of this study is to investigate its
      putative role in the transdifferentiation of Tenon's fibroblasts to
      myofibroblasts. METHODS: Primary cultured human Tenon's fibroblasts were exposed
      to transforming growth factor-beta1 (TGF-beta1) for up to 48 hours. The mRNA
      levels of Hsp47 and alpha smooth muscle actin (alphaSMA) were determined by
      quantitative real time RT-PCR. After delivery of small interfering RNA (siRNA)
      molecules targeting Hsp47 into the cells, the expression of Hsp47 and alphaSMA
      proteins was determined by western immunoblotting. RESULTS: TGF-beta1 increased
      the mRNA expressions of both Hsp47 and alphaSMA in human Tenon's fibroblasts, as
      determined by quantitative real time RT-PCR. However, it induced the protein
      expression of only alphaSMA but not Hsp47, as determined by western immunoblots.
      When siRNAs specific for Hsp47 were introduced into those cells, the TGF-beta1
      induced expression of alphaSMA was significantly attenuated on western
      immunoblots; after 48 hours of exposure to TGF-beta1, the relative densities of
      immunobands were 11.58 for the TGF-beta1 only group and 2.75 for the siRNA
      treatment group, compared with the no treatment control group (p < 0.001).
      CONCLUSIONS: Our data suggest that Hsp47 may be related to the TGF-beta1-induced
      transdifferentiation of human Tenon's fibroblasts to myofibroblasts.

PMID- 22967134
TI  - Coordinability and consistency in accident causation and prevention: formal
      system theoretic concepts for safety in multilevel systems.
AB  - Although a "system approach" to accidents in sociotechnical systems has been
      frequently advocated, formal system theoretic concepts remain absent in the
      literature on accident analysis and system safety. To address this gap, we
      introduce the notions of coordinability and consistency from the hierarchical and
      multilevel systems theory literature. We then investigate the applicability and
      the importance of these concepts to accident causation and safety. Using
      illustrative examples, including the worst disaster in aviation history, and
      recent incidents in the United States of aircraft clipping each other on the
      tarmac, we propose that the lack of coordinability is a fundamental failure
      mechanism causing or contributing to accidents in multilevel systems. We make a
      similar case for the lack of consistency. Coordinability and consistency become
      ingredients for accident prevention, and their absence fundamental failure
      mechanisms that can lead to system accidents. Finally, using the concepts
      introduced in this work, we identify several venues for further research,
      including the development of a theory of coordination in multilevel systems, the
      investigation of potential synergies between coordinability, consistency, and the
      high reliability organizations paradigm, and the possibility of reframing the
      view that "sloppy management is the root cause of many industrial accidents" as
      one of lack of coordinability and/or consistency between management and
      operations. By introducing and expanding on the concepts of coordinability and
      consistency, we hope to contribute to the thinking about, and the to language of,
      accident causation, and prevention and to add to the intellectual toolkit of
      safety professionals and academics.

PMID- 22967133
TI  - Genetically encodable design of ligand "bundling" on the surface of
      nanoparticles.
AB  - Polyhistidine peptide dendrimer self-assembles on CdSe/ZnS quantum dots (QDs)
      with very high affinity and stability, a property ascribable to its multivalent
      geometry. Here we designed a fluorescent protein, GCN-mCherry, that exists as an
      oligomeric bundled structure in solution as well as on the surface to imitate the
      structure of a synthetic dendrimer. GCN-mCherry forms a very stable assembly with
      QDs, which can resist displacement by 500 mM imidazole and the dendrimer peptide,
      as measured by the Forster resonance energy transfer from QD to mCherry. Our work
      manifested a prominent stability enhancement of  protein-nanoparticle assembly
      through directional ligand-ligand interaction on the surface.

PMID- 22967135
TI  - Transumbilical single port laparoscopic surgery for the treatment of concomitant
      disease.
AB  - BACKGROUND: We report our experience of transumbilical single port laparoscopic
      surgery (TUSPLS) for multiple concomitant intraabdominal pathologies, and assess
      the feasibility of this technique with several technical tips. METHODS: Various
      combined procedures using TUSPLS were performed since April, 2008. All records of
      concomitant laparoscopic procedures using TUSPLS were searched at three
      hospitals. RESULTS: Forty-one patients underwent 82 combined procedures using
      TUSPLS in a single session. The perioperative outcomes of simultaneously
      performed cholecystectomy and ovarian cystectomy using TUSPLS (n = 14) are
      compared with those of using CLS (n = 11). The operating time was significantly
      longer with the TUSPLS method than with the CLS method. However, postoperative
      convalescent outcomes such as postoperative hospital stay, VAS pain score, and
      required analgesics showed no differences between the two methods. Also, there
      were no significant operative complications associated with the two methods.
      Fewer trocars were used with the TUSPLS method. CONCLUSIONS: Combined
      laparoscopic procedures for various concomitant pathologies in the abdomen can be
      performed using transumbilical single port laparoscopic surgery without
      increasing morbidity or hospital stay in patients with acceptable risk.

PMID- 22967136
TI  - Coronary ostium topography: an implication for transcatheter aortic valve
      implantation?
AB  - OBJECTIVES: Shorter distances from coronary ostia to the calcified aortic valve
      may result in occlusion with potential infarction during transcatheter aortic
      valve implantation. We hypothesized that preoperative CT-scan measurements might
      predict coronary occlusion. METHODS: Distances from the coronary ostia to the
      calcified aortic valve were measured during open heart aortic valve replacement
      in 60 consecutive patients. Distances were compared to preoperative CT-scan
      measurements evaluating distance of the coronary ostia as well (n = 15). RESULTS:
      The distances of the lower lip of the left and the right coronary artery ostia
      measured from the aortic annulus were 14.7 +/- 3.9 mm and 13.4 +/- 4.0 mm,
      respectively. The left, right and noncoronary cusp heights were 13.9 +/- 2.5 mm,
      12.8 +/- 3.0 mm and 13.3 +/- 3.1 mm, respectively. Coronary ostia topography
      indicated variations from the middle to the noncoronary commissure in 40% for the
      left and 63% for the right coronary ostium. CT-scan based measurements resulted
      in a distance of 12.8 +/- 3.5 mm for the left and 13.9 +/- 4.0 mm for the right
      coronary ostium, compared to 14.2 +/- 4.2 mm and 13.5 +/- 4.3 mm measured
      intraoperatively. A mild correlation between both measurements could be observed
      (r = 0.374, P = 0.188, left and r = 0.46, P = 0.09, n = 15). CONCLUSIONS: CT-scan
      based measurements differed from the intraoperative measurements, however
      preoperative CT-scan evaluation may be a useful tool to identify patients with
      short distance of coronaries.

PMID- 22967137
TI  - 320-detector-row computed tomography arteriography using CO2 gas to detect
      malignant liver tumors.
AB  - PURPOSE: We present the initial steps for 320-detector-row computed tomography
      arteriography using CO2 gas (320-MDCT CO2 arteriography) to detect the vascular
      area of malignant liver tumors. MATERIAL AND METHODS: This study was approved by
      the Ethics Committee of our institution. Written prior informed consent was
      obtained from all patients. We studied six patients with primary and metastatic
      liver tumors (n = 26) and allergic reactions to iodinated contrast media or a
      tendency for renal failure. CO2 was injected at 1 ml/sec (volume 8 ml) into the
      common hepatic artery and a CT scan was acquired 12 seconds after the start of
      injection. The detection of the vascular area of the tumor or of intratumor air
      was evaluated with respect to the relationship between the size and location of
      the tumors. Cramer's V statistic was performed to explore the relationship (p <
      0.05). RESULTS: The vascular area was detected in 17 of the 26 tumors (65.4%).
      There was a correlation between the detection of the adjacent vascular area on
      CTA images acquired with the use of CO2 and the tumor site observed on previously
      acquired MRI or CT images. CONCLUSION: 320-MDCT CO2 arteriography with
      microcatheters may be useful for the detection of the vascular area.

PMID- 22967138
TI  - Preparation of cationic nanogels for nucleic acid delivery.
AB  - Cationic nanogels with site-selected functionality were designed for the delivery
      of nucleic acid payloads targeting numerous therapeutic applications. Functional
      cationic nanogels containing quaternized 2-(dimethylamino)ethyl methacrylate and
      a cross-linker with reducible disulfide moieties (qNG) were prepared by
      activators generated by electron transfer (AGET) atom transfer radical
      polymerization (ATRP) in an inverse miniemulsion. Polyplex formation between the
      qNG and nucleic acid exemplified by plasmid DNA (pDNA) and short interfering RNA
      (siRNA duplexes) were evaluated. The delivery of polyplexes was optimized for the
      delivery of pDNA and siRNA to the  Drosophila  Schneider 2 (S2) cell-line. The
      qNG/nucleic acid (i.e., siRNA and pDNA) polyplexes were found to be highly
      effective in their capabilities to deliver their respective payloads.

PMID- 22967139
TI  - NDMA formation by chloramination of ranitidine: kinetics and mechanism.
AB  - The kinetics of decomposition of the pharmaceutical ranitidine (a major precursor
      of NDMA) during chloramination was investigated and some decomposition byproducts
      were identified by using high performance liquid chromatography coupled with mass
      spectrometry (HPLC-MS). The reaction between monochloramine and ranitidine
      followed second order kinetics and was acid-catalyzed. Decomposition of
      ranitidine formed different byproducts depending on the applied monochloramine
      concentration. Most identified products were chlorinated and hydroxylated
      analogues of ranitidine. In excess of monochloramine, nucleophilic substitution
      between ranitidine and monochloramine led to byproducts that are critical
      intermediates involved in the formation of NDMA, for example, a carbocation
      formed from the decomposition of the methylfuran moiety of ranitidine. A complete
      mechanism is proposed to explain the high formation yield of NDMA from
      chloramination of ranitidine. These results are of great importance to understand
      the formation of NDMA by chloramination of tertiary amines.

PMID- 22967140
TI  - Role of oestrogen receptors on the modulation of NADPH-diaphorase-positive cell
      number in supraoptic and paraventricular nuclei of ovariectomised female rats.
AB  - Modulation of the nitric oxide producing system (demonstrated via the NADPH
      diaphorase histochemical reaction) by oestradiol has been established in several
      structures of the rat brain. The present study aimed to explore the possible
      regulation of NADPH-diaphorase activity by oestradiol in neurones of the
      supraoptic (SON) and paraventricular (PVN) nuclei and the role of oestrogen
      receptors (ERalpha and ERbeta) in this regulation. Adult ovariectomised rats were
      divided into six groups and injected either with vehicle or a single dose of
      oestradiol, a selective ERalpha agonist-PPT [4,4',4"-(4-propyl-[1H]-pyrazole
      1,3,5-triyl)trisphenol], a selective ERbeta agonist-DPN [2,3-bis(4-hydroxyphenyl)
      propionitrile], a selective ERalpha antagonist-MPP [1,3-bis(4-hydroxyphenyl)-4
      methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride] or a
      selective ERbeta antagonist-PHTPP (4-[2-phenyl-5,7
      bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol). The number of NADPH
      diaphorase positive elements in the SON and the PVN was modulated by both ERs
      but, depending on the nucleus, ERalpha and ERbeta ligands induced different
      effects. These results suggest that the regulation of nitrergic system by ERs may
      play a role in the control of oestrogen-dependent physiological mechanisms
      regulated by the SON and the PVN.

PMID- 22967141
TI  - High SSR diversity but little differentiation between accessions of Nordic
      timothy (Phleum pratense L.).
AB  - A large collection of genebank accessions of the hexaploid outcrossing forage
      grass species timothy (Phleum pratense L.) was for the first time analysed for
      SSR diversity on individual, population and regional level. Timothy is the most
      important forage grass species in the Nordic countries. Eighty-eight timothy
      accessions from Nordic countries and eight accessions around Europe were analysed
      with recently developed simple sequence repeat (SSR) markers. Timothy proved to
      be very polymorphic: the 13 selected SSRs amplified a total of 499 polymorphic
      alleles, the number of alleles per SSR locus varying from 15 to 74. Taking all
      SSR alleles together, the observed number in each accession ranged from 95 to
      203. Levels of diversity were found to be significantly different between
      countries, vegetation zones and different cultivar types. However, the
      differentiation between accessions was low: most of the variation (94%) in the
      studied timothy material was due to variation within accessions and only 5% was
      between accessions and 1% between countries. Lack of geographical differentiation
      may reflect the outcrossing and hexaploid nature of timothy. Our results showed
      that neutral SSR markers are suitable for demonstrating levels of diversity but
      not alone adequate to resolve population structure in timothy. Nordic timothy
      material seems to be diverse enough for breeding purposes and no decline in the
      level of diversity was observed in varieties compared to wild timothy
      populations. Challenges in analysing SSR marker data in a hexaploid outcrosser
      were discussed.

PMID- 22967142
TI  - Chromosomal evolution in the South American Riodinidae (Lepidoptera:
      Papilionoidea).
AB  - We give the haploid chromosome numbers of 173 species or subspecies of Riodinidae
      as well as of 17 species or subspecies of neotropical Lycaenidae for comparison.
      The chromosome numbers of riodinids have thus far been very poorly known. We find
      that their range of variation extends from n = 9 to n = 110 but numbers above n =
      31 are rare. While lepidopterans in general have stable chromosome numbers, or
      variation is limited at most a subfamily or genus, the entire family Riodinidae
      shows variation within genera, tribes and subfamilies with no single modal
      number. In particular, a stepwise pattern with chromosome numbers that are about
      even multiples is seen in several unrelated genera. We propose that this
      variation is attributable to the small population sizes, fragmented populations
      with little migration, and the behavior of these butterflies. Small and isolated
      riodinid populations would allow for inbreeding to take place. Newly arisen
      chromosomal variants could become fixed and contribute to reproductive isolation
      and speciation. In contrast to the riodinids, the neotropical Lycaenidae
      (Theclinae and Polyommatinae) conform to the modal n = 24 that characterizes the
      family.

PMID- 22967143
TI  - Connection between rod bivalents and incomplete meiotic association at NORs in
      Hordeum marinum Huds.
AB  - The hypothesis of a connection between rod bivalent formation and incomplete
      meiotic association at NORs of SAT-chromosomes of H. marinum is supported. PMCs
      of H. marinum ssp. gussoneanum (2x), two diploid ssp. marinum * ssp. gussoneanum
      (2x) hybrids and two ssp. gussoneanum (4x) * Secale cereale hybrids at metaphase
      I (M-I) were analyzed by in situ hybridization. The probe pTa71 labelled rDNA
      sites at NORs of a single pair of homologous or near-homologous SAT-chromosomes
      of H. marinum in each material. In the three diploids, M-I was regular with ring
      bivalents and one or a few rods (av.13.52 bound arms cell(-1)). More rod
      bivalents than the expected one out of seven, i.e. 30, 67 and 89% included rDNA
      carrying chromosomes. Corresponding bound short arm frequencies were 0.89, 0.72
      and 0.52, while long arms and arms of other chromosomes presented complete or
      near- complete association. The two heterogenomic hybrids had a less regular M-I
      (av. 8.04 bound arms cell(-1)) including 20% rDNA-carrying rods with bound arm
      frequencies of 0.29 in short and 0.87 in long arms. Positions of chromosome
      associations were established in all 150 rDNA-carrying bivalents. In 77 bivalents
      with short arm associations, 4% of these occurred proximally to, none at, and 96%
      distally to rDNA sites, i.e. in satellites. In 143 bivalents with long arm
      associations, 83% occurred at interstitial and 17% at terminal positions. The
      observations combine increased frequency of rDNA-carrying rods with decreased
      frequency of association at NOR regions of SAT-chromosomes. The basis for the
      relationship is discussed.

PMID- 22967144
TI  - Molecular mapping of stripe rust resistance gene YrSN104 in Chinese wheat line
      Shaannong 104.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a serious
      yield-limiting factor for wheat production worldwide. The objective of this study
      was to identify and map a stripe rust resistance gene in wheat line Shaannong 104
      using SSR markers. F(1), F(2) and F(3) populations from Shaannong 104/Mingxian
      169 were inoculated with Chinese Pst race CYR32 in a greenhouse. Shaannong 104
      carried a single dominant gene, YrSN104. Six potential polymorphic SSR markers
      identified in bulk segregant analysis were used to genotype F(2) and F(3)
      families. YrSN104 was closely linked with all six SSR markers on chromosome 1BS
      with genetic distances of 2.0 cM (Xgwm18, Xgwm273, Xbarc187), 2.6 cM (Xgwm11,
      Xbarc137) and 5.9 cM (Xbarc240). Pedigree analysis, pathogenicity tests using 26
      Pst races, haplotyping of associated markers on isogenic lines carrying known
      stripe rust resistance genes, and associations with markers suggested that
      YrSN104 was a new resistance gene or an allele at the Yr24/Yr26 locus on
      chromosome 1BS. Deployment of YrSN104 singly or in combination to elite genotypes
      could play an effective role to lessen yield losses caused by stripe rust.

PMID- 22967145
TI  - Introducing GUt low-density array (GULDA): a validated approach for qPCR-based
      intestinal microbial community analysis.
AB  - Alterations in the human gut microbiota caused, for example, by diet, functional
      foods, antibiotics, or occurring as a function of age are now known to be of
      relevance for host health. Therefore, there is a strong need for methods to
      detect such alterations in a rapid and comprehensive manner. In the present
      study, we developed and validated a high-throughput real-time quantitative PCR
      based analysis platform, termed 'GUt Low-Density Array' (GULDA). The platform was
      designed for simultaneous analysis of the change in the abundance of 31 different
      microbial 16S rRNA gene targets in fecal samples obtained from individuals at
      various points in time. The target genes represent important phyla, genera,
      species, or other taxonomic groups within the five predominant bacterial phyla of
      the gut, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and
      Verrucomicrobia and also Euryarchaeota. To demonstrate the applicability of
      GULDA, analysis of fecal samples obtained from six healthy infants at both 9 and
      18 months of age was performed and showed a significant increase over time of the
      relative abundance of bacteria belonging to Clostridial cluster IV (Clostridia
      leptum group) and Bifidobacterium bifidum and concurrent decrease in the
      abundance of Clostridium butyricum and a tendency for decrease in
      Enterobacteriaceae over the 9-month period.

PMID- 22967146
TI  - Dual-color imaging of magnesium/calcium ion activities with two-photon
      fluorescent probes.
AB  - We report two-photon probes (FMg1 and FMg2) that can selectively detect
      intracellular free Mg(2+) ([Mg(2+)](i)) in live cells and tissues by two-photon
      microscopy. Combined with BCaM, a two-photon probe for near-membrane Ca(2+)
      ([Ca(2+)](m)), FMg2 allows dual-color imaging of Mg(2+)/Ca(2+) activities in live
      cells and [Mg(2+)](i) /[Ca(2+)](m) distributions in live tissues at a depth of
      100-200 MUm.

PMID- 22967147
TI  - The clinical utility of health-related quality of life assessment in pediatric
      cardiology outpatient practice.
AB  - OBJECTIVES: Children with congenital heart disease may experience significant
      psychosocial morbidity related to impaired quality of life (QOL). The aim of this
      study was to evaluate the clinical utility of health-related QOL assessment in a
      pediatric cardiology outpatient clinic. DESIGN: The Pediatric Quality of Life
      Inventory (PedsQL) 4.0 Generic Core Scales were completed by a convenience sample
      of 176 patients, aged 8-18 years, being seen in a pediatric cardiology clinic.
      Three cardiologists enrolled in this study reviewed the completed PedsQL during
      the clinic visit and recorded their responses to items reported to be a problem
      "Often" or "Almost Always." This utilization of the instrument was compared to
      standardized scoring and the practicality and perceived usefulness of the
      practice was evaluated by physician interview. RESULTS: PedsQL responses showed
      38% of patients reporting significant (Often or Almost Always) problems on at
      least one domain (19% Physical Functioning, 18.2% Emotional Functioning, 11.4%
      Social Functioning, and 22.3% School Functioning problems). Using standardized
      scoring, the prevalence of scores below the cutoff score for clinically
      significant impaired QOL in each domain ranged from 10% to 20%, with agreement
      between scoring methods ranging from 89% to 93%, sensitivity 68% to 86%, and
      specificity 89% to 97%. Cardiologists reported interventions in 30.1% of
      patients. They found that the PedsQL was easy to use, did not interfere with
      clinic operations, required minimal time (1-5 minutes), and provided information
      that had an important impact on their practice in some patients. CONCLUSIONS:
      This study demonstrates the clinical utility of health-related QOL assessment
      using the PedsQL in a pediatric cardiology outpatient setting. Identification of
      significant impairments in QOL can impact clinical decision making and may change
      psychosocial outcomes in children with congenital heart disease.

PMID- 22967148
TI  - A multi-scale mechanobiological model of in-stent restenosis: deciphering the
      role of matrix metalloproteinase and extracellular matrix changes.
AB  - Since their first introduction, stents have revolutionised the treatment of
      atherosclerosis; however, the development of in-stent restenosis still remains
      the Achilles' heel of stent deployment procedures. Computational modelling can be
      used as a means to model the biological response of arteries to different stent
      designs using mechanobiological models, whereby the mechanical environment may be
      used to dictate the growth and remodelling of vascular cells. Changes occurring
      within the arterial wall due to stent-induced mechanical injury, specifically
      changes within the extracellular matrix, have been postulated to be a major cause
      of activation of vascular smooth muscle cells and the subsequent development of
      in-stent restenosis. In this study, a mechanistic multi-scale mechanobiological
      model of in-stent restenosis using finite element models and agent-based
      modelling is presented, which allows quantitative evaluation of the collagen
      matrix turnover following stent-induced arterial injury and the subsequent
      development of in-stent restenosis. The model is specifically used to study the
      influence of stent deployment diameter and stent strut thickness on the level of
      in-stent restenosis. The model demonstrates that there exists a direct
      correlation between the stent deployment diameter and the level of in-stent
      restenosis. In addition, investigating the influence of stent strut thickness
      using the mechanobiological model reveals that thicker strut stents induce a
      higher level of in-stent restenosis due to a higher extent of arterial injury.
      The presented mechanobiological modelling framework provides a robust platform
      for testing hypotheses on the mechanisms underlying the development of in-stent
      restenosis and lends itself for use as a tool for optimisation of the mechanical
      parameters involved in stent design. 

PMID- 22967149
TI  - The international assembly of pediatric anesthesiologists.

PMID- 22967150
TI  - Breaking down the borders of patient safety.

PMID- 22967151
TI  - Safe perioperative pediatric care around the world.
AB  - Pediatric anesthesia is no longer a small subspecialty, but an important sector
      where developments in the new century have brought effective and safe management
      to children in the perioperative period. Unfortunately, what is common daily
      practice in the high-income countries with all the guidelines, checklists,
      instruments, and dedicated pediatric anesthesiologists is often only a dream in
      the low- and middle-income countries where the basic anesthesia services for
      improving the high rate of morbidity and mortality still are lacking. Anesthesia
      given by nonphysicians, with no monitoring, lack of elementary supplies, poor
      control of infections and hemorrhage, and no water or electricity are very often
      the 'usual' conditions. The World Health Organization is working hard to offer
      teams, basic equipments, and teaching and what is needed to offer children of
      these countries the same opportunities given in the industrialized countries.
      Other projects such as the Lifebox Project have a similar aim. This paper
      outlines some of what organizations are doing around the world, with different
      strategies all having the same target: safe pediatric anesthesia.

PMID- 22967152
TI  - New technologies in pediatric anesthesia.
AB  - This article reviews potential pediatric applications of 3 new technologies. (1)
      Pulse oximetry-based hemoglobin determination: Hemoglobin determination using
      spectrophotometric methods recently has been introduced in adults with varied
      success. This non-invasive and continuous technology may avoid venipuncture and
      unnecessary transfusion in children undergoing surgery with major blood loss,
      premature infants undergoing unexpected and complicated emergency surgery, and
      children with chronic illness. (2) Continuous cardiac output monitoring: In
      adults, advanced hemodynamic monitoring such as continuous cardiac output
      monitoring has been associated with better surgical outcomes. Although it remains
      unknown whether similar results are applicable to children, current technology
      enables the monitoring of cardiac output non-invasively and continuously in
      pediatric patients. It may be important to integrate the data about cardiac
      output with other information to facilitate therapeutic interventions. (3)
      Anesthesia information management systems: Although perioperative electronic
      anesthesia information management systems are gaining popularity in operating
      rooms, their potential functions may not be fully appreciated. With advances in
      information technology, anesthesia information management systems may facilitate
      bedside clinical decisions, administrative needs, and research in the
      perioperative setting.

PMID- 22967153
TI  - International advocacy for education and safety.
AB  - Surgical safety has emerged as a significant global public health concern with
      reported mortality rates varying tremendously between developing and
      industrialized countries. This manuscript reviews some of the challenges
      encountered in providing safe anesthesia care in the humanitarian space;
      identifies the difficulties with providing high-quality education in developing
      countries; and describes how audits and quality improvement databases enhance our
      understanding of the nature and causes of harm to patients to inform the
      development of strategies for improvement.

PMID- 22967154
TI  - SmartTots: a public-private partnership between the United States Food and Drug
      Administration (FDA) and the International Anesthesia Research Society (IARS).
AB  - A history of the public-private partnership 'SmartTots' between the IARS and FDA
      is presented. In order to raise money for research to better understand the
      relationship between sedative and anesthetic agents and neurotoxicity in the
      developing brain, the FDA approached the IARS in 2008. A partnership was
      developed over the following 2 years, then a Scientific Advisory Board was
      created to develop a research agenda. The IARS contributed $200 000 in 2011 to
      provide initial funding; 33 proposals were submitted in response to a request for
      proposals in late 2011 and resulted in the awarding of two, $100 000 grants in
      2012. An Executive Board was appointed under the leadership of Michael Roizen to
      spearhead additional fund-raising efforts, and a director of development is
      working with Dr. Roizen and the Board to raise funds from individuals and
      organizations. Dr. Roizen has personally committed to a matching grant for
      anesthesiologists, up to $50 000 per year for 20 years ($1 million). Readers of
      the journal are encouraged to go to the website www.smarttots.org in order to
      better understand the issue, to contribute to the research fund themselves, and
      to encourage their own professional organizations to partner with SmartTots in
      fund-raising.

PMID- 22967155
TI  - Anesthetics and the developing brain: time for a change in practice? A pro/con
      debate.

PMID- 22967156
TI  - Is nitrous oxide necessary in the future?

PMID- 22967157
TI  - Simulation in pediatric anesthesiology.
AB  - Simulation-based training, research and quality initiatives are expanding in
      pediatric anesthesiology just as in other medical specialties. Various modalities
      are available, from task trainers to standardized patients, and from computer
      based simulations to mannequins. Computer-controlled mannequins can simulate
      pediatric vital signs with reasonable reliability; however the fidelity of skin
      temperature and color change, airway reflexes and breath and heart sounds remains
      rudimentary. Current pediatric mannequins are utilized in simulation centers,
      throughout hospitals in-situ, at national meetings for continuing medical
      education and in research into individual and team performance. Ongoing efforts
      by pediatric anesthesiologists dedicated to using simulation to improve patient
      care and educational delivery will result in further dissemination of this
      technology. Health care professionals who provide complex, subspecialty care to
      children require a curriculum supported by an active learning environment where
      skills directly relevant to pediatric care can be developed. The approach is not
      only the most effective method to educate adult learners, but meets calls for
      education reform and offers the potential to guide efforts toward evaluating
      competence. Simulation addresses patient safety imperatives by providing a method
      for trainees to develop skills and experience in various management strategies,
      without risk to the health and life of a child. A curriculum that provides
      pediatric anesthesiologists with the range of skills required in clinical
      practice settings must include a relatively broad range of task-training devises
      and electromechanical mannequins. Challenges remain in defining the best
      integration of this modality into training and clinical practice to meet the
      needs of pediatric patients.

PMID- 22967158
TI  - Everyday regional anesthesia in children.
AB  - Regional anesthesia in children is an evolving technique with many advantages in
      perioperative management. Although most regional anesthesia techniques are
      sufficiently described in the literature, the implementation of these techniques
      into daily clinical practice is still lacking. The main problems associated with
      pediatric regional anesthesia (PRA) include the appropriate selection of
      blockade, the management around the block, and how to teach these techniques in
      an optimal manner. This review article provides an overview of these 'hot' topics
      in PRA.

PMID- 22967159
TI  - Ultrasound for vascular access in pediatric patients.
AB  - OBJECTIVES: In pediatric patients vascular access is often more difficult than in
      adults because of the smaller size of the vessels and the inability of the
      patient to cooperate without deep sedation or general anesthesia. Therefore
      Ultrasound has already become an invaluable tool for vascular access, but the
      full potential of ultrasound has yet to be fully realized. Improvements in image
      quality and a better understanding of optimal insertion techniques continue to
      help clinicians safely and efficiently place catheters with fewer complications.
      METHODS AND TECHNIQUE: The probes used for the vascular access are mainly linear
      and convex type. Higher- frequency ultrasound provides a vivid image; however,
      the signals are remarkably attenuated. Therefore, the choice of the probe with
      appropriate frequency is essential. As blood vessels are relatively easily
      identified with ultrasound, ultrasound-guided vascular access does not require as
      sharp images as ultrasound-guided nerve block. For pediatric vascular access, the
      linear probe with 5-15 MHz, 2-5 cm depth is ideal and adequate for almost all
      cases. Ultrasound-guided vascular access has two main approaches: 'long-axis' or
      'in-plane approach' and 'short-axis' or 'transverse approach'. The long-axis
      approach visualizes the vessel along the insertion pathway and is commonly used
      to monitor the entire approach of the needle into the vessel. The short-axis
      approach is easier to show the positional relationship and depth of target
      vessels, but it is much harder to follow the needle tip within the tissues.
      CONCLUSION: The use of 'real-time' ultrasound has been shown to increase first
      insertion success, reduce access time, have a higher overall success, and reduce
      arterial puncture. As the technology continues to improve the use of ultrasound
      will become as ubiquitous as the lines themselves.

PMID- 22967160
TI  - Pediatric airway management: current practices and future directions.
AB  - Management of a pediatric airway can be a challenge, especially for the non
      pediatric anesthesiologists. Structured algorithms for an unexpected difficult
      pediatric airway have been missing so far. A recent step wise algorithm, based on
      the Difficult Airway society (DAS) adult protocol, is a step in the right
      direction. There have been some exciting advances in development of pediatric
      extra-glottic devices for maintaining ventilation, and introduction of pediatric
      versions of new 'non line of sight' laryngoscopes and optical stylets. The exact
      role of these devices in routine and emergent situations is still evolving.
      Recent advances in simulation technology has become a valuable tool in imparting
      psychomotor and procedural skills to trainees and allied healthcare workers.
      Moving toward the goal of eliminating serious adverse events during the
      management of routine and difficult pediatric airway, authors propose that
      institutions develop a dedicated Difficult Airway Service comprising of a team of
      experts in advanced airway management.

PMID- 22967161
TI  - Developing a pediatric pain service.
AB  - Pediatric pain services were first established in larger pediatric centers over
      two decades ago. Children's acute pain was poorly managed at the time owing to
      misconceptions, safety concerns, and variability in practice. While many larger
      pediatric centers now have acute pain services, there remains a need for better
      pain management in facilities and geographic locations with fewer resources.
      Institutional acknowledgement and desire to change, appropriate staffing, and
      funding are major obstacles. Better recognition and assessment as well safer and
      more efficacious treatment of pain are the principal objectives when establishing
      a pain service. It is important to determine whether the proposed service intends
      to treat acute, chronic, procedural, and/or cancer and palliative pain as each
      requires different skills and resources. An ideal and comprehensive pediatric
      pain service should be equipped to diagnose and treat acute, persistent
      (chronic), procedural, and cancer/palliative pain. It is not feasible or
      necessary for every hospital to manage all. Establishing the scope of practice
      (based on case mix and caseload) in any given hospital will determine which
      resources are desired. Country-specific standards, local staffing, and fiscal
      constraints will influence which resources are available.

PMID- 22967162
TI  - Implementing checklists in the operating room.
AB  - Checklists have established themselves as a key safety process in the operating
      room environment. This paper describes the background and context of how
      checklists have evolved in medicine. It also highlights ongoing challenges with
      particular attention to the importance of nontechnical skills or human factors
      training with relation to checklist design, testing and implementation and
      ongoing coaching.

PMID- 22967164
TI  - The influence of the macro-environment on physical activity: a multilevel
      analysis of 38 countries worldwide.
AB  - BACKGROUND: As indicated by the ANGELO framework and similar models, various
      environmental factors influence population levels of physical activity (PA). To
      date attention has focused on the micro-level environment, while evidence on the
      macro-level environment remains scarce and mostly limited to high-income
      countries. This study aims to investigate whether environmental factors at macro
      level are associated with PA among a broader range of countries. METHODS: Data
      from the World Health Survey (WHS) was used to analyze 177,035 adults from 38
      (mostly low and middle income) countries. The International Physical Activity
      Questionnaire-Short Form (IPAQ-S) was used to measure PA. Respondents were
      classified as active or inactive for vigorous PA, moderate PA and walking.
      Multilevel logistic regression was performed to assess associations between macro
      level environmental factors and the prevalence of PA, with control for individual
      level socioeconomic factors. RESULTS: The prevalence of PA varied widely between
      countries and types of PA (5.0%-93.8%). A negative association was found between
      gross domestic product and PA, odds ratios for men were 0.76 (95% CI: 0.65-0.89)
      for moderate PA and 0.79 (95% CI: 0.63-0.98) for walking. A higher temperature
      was associated with less PA (all types) and higher urbanization was associated
      with less vigorous and moderate PA. More gender equality was also associated with
      more walking for women. Governmental functioning and literacy rate were not found
      to be associated with any type of PA. CONCLUSIONS: This exploratory study
      indicates that factors such as climate, economic development and cultural factors
      are determinants of the level of overall PA at national levels. This underlines
      the suggestion that the macro-environment should be regarded as an important
      influence on PA.

PMID- 22967166
TI  - Comparative efficacy of biologics in psoriasis: a review.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated skin disease that also has
      systemic manifestations. Safe and effective long-term treatments are needed.
      Biologic treatments that inhibit the immunopathogenesis of psoriasis have helped
      meet this need. PURPOSE: The purpose of this study was to compare the efficacy of
      biologic therapies used for psoriasis. METHODS: A literature search was performed
      using PubMed and the keywords '(PASI-75 OR efficacy) AND psoriasis AND
      (adalimumab OR alefacept OR etanercept OR infliximab OR ustekinumab).'
      Randomized, double-blind, and placebo-controlled studies on US FDA-approved
      biologics were selected. Studies assessing the proportion of subjects achieving
      75% improvement in Psoriasis Area and Severity Index (PASI-75) within a 12-week
      period were included. Studies on pediatric populations and psoriatic arthritis
      were excluded. The weighted average of PASI-75 for each reported regimen was
      calculated to determine the efficacy of biologic agents used for moderate-to
      severe psoriasis. Tolerance and secondary efficacy measures were also examined
      for the selected studies. RESULTS: FDA-approved regimens of adalimumab,
      infliximab, ustekinumab, and alefacept were effective in treating moderate-to
      severe psoriasis. Weighted average PASI-75 scores for infliximab, ustekinumab,
      adalimumab, etanercept, and alefacept were 78.6%, 72.1%, 70.5%, 48.1%, and 21%,
      respectively. LIMITATIONS: The comparative efficacy of biologic agents data was
      limited to 12 weeks, thus generalizing the results to longer treatment periods
      may not be accurate. CONCLUSIONS: Various biologic agents for psoriasis were
      effective at 12 weeks in placebo-controlled trials. Available data cannot fully
      account for situations in clinical practice, in which combination and longer
      duration of therapy may be required. When choosing the most effective or best
      agent, multiple factors should be considered including patient preference, cost,
      tolerance, adverse effects, dosing schedule, and mode of administration.

PMID- 22967165
TI  - Eurycoma longifolia upregulates osteoprotegerin gene expression in androgen-
      deficient osteoporosis rat model.
AB  - BACKGROUND: Eurycoma longifolia (EL) has been shown recently to protect against
      bone calcium loss in orchidectomised rats, the model for androgen-deficient
      osteoporosis. The mechanism behind this is unclear but it may be related to its
      ability to elevate testosterone levels or it may directly affect bone remodeling.
      The aim of this study is to determine the mechanism involved by investigating the
      effects of EL extract on serum testosterone levels, bone biomarkers,
      biomechanical strength and gene expression of Receptor Activator of Nuclear
      Factor kappa-B ligand (RANKL), Osteoprotegerin (OPG) and Macrophage-Colony
      Stimulating Factor (MCSF) in orchidectomised rats. METHODS: Thirty-two male
      Sprague-Dawley rats were divided into: Sham-operated group (SHAM);
      orchidectomised-control group (ORX); orchidectomised and given 15 mg/kg EL
      extract (ORX + EL) and orchidectomised and given 8 mg/kg testosterone (ORX + T).
      The rats were treated for 6 weeks. The serum levels of testosterone, osteocalcin
      and C-terminal telopeptide of type I collagen (CTX) were measured using the ELISA
      technique. The femoral bones were subjected to biomechanical testing. The tibial
      bone gene expressions of RANKL, OPG and MCSF were measured using the branch DNA
      technique. RESULTS: The post-treatment level of testosterone was found to be
      significantly reduced by orchiectomy (p < 0.05). Both ORX + EL and ORX + T groups
      have significantly higher post-treatment testosterone levels compared to their
      pre-treatment levels (p < 0.05). The bone resorption marker (CTx) was elevated
      after orchiectomy but was suppressed after treatment in the ORX + EL and ORX + T
      groups (p < 0.05). There was no significant finding for the femoral biomechanical
      parameters. The tibial OPG gene expression in the ORX group was significantly
      lower compared to the SHAM and ORX + EL groups (p < 0.05). CONCLUSION:
      Supplementation with EL extract elevated the testosterone levels, reduced the
      bone resorption marker and upregulated OPG gene expression of the orchidectomised
      rats. These actions may be responsible for the protective effects of EL extract
      against bone resorption due to androgen deficiency.

PMID- 22967167
TI  - Mechanism study of the intramolecular anti-Michael addition of N
      alkylfurylacrylacetamides.
AB  - The mechanism of the intramolecular nucleophilic addition of N
      alkylfurylacrylacetamides is investigated by density functional theory
      calculations. Three possible reaction pathways have been considered based on
      possible conformations of the same reactant, which undergoes three stages,
      including hydrogen elimination by the base NaH, followed by the nucleophilic
      addition of N(-) on C(alpha) (C(beta)) via an anti-Michael (Michael) mechanism,
      and then proton transfer affords the final product Pr-5 (Pr-6). The pathway
      corresponding to the reactant with the most stable conformation is found to be
      the most favorable one. The rate-determining step of the intramolecular
      nucleophilic addition is the nucleophilic addition of N(-) on C(alpha) (C(beta))
      featuring a cyclic ring transition state. Solvent effects are considered at the
      B3LYP/6-31G(d,p) level in solvent DMSO, and the results suggest that the relative
      reaction trends are consistent with the gas-phase reaction. Furthermore, the
      difference of the energy barriers explains the origin of the regioselectivity of
      the experiment. Finally, the effects of the substituent on N1 and C(beta) to the
      regioselectivity have been discussed.

PMID- 22967168
TI  - An amphiphilic pillar[5]arene: synthesis, controllable self-assembly in water,
      and application in calcein release and TNT adsorption.
AB  - An amphiphilic pillar[5]arene was made. It could self-assemble to form vesicles
      and multiwalled microtubes in water. Dynamic light scattering, transmission
      electron microscopy, scanning electron microscopy, atomic force microscopy, and
      UV-vis and FTIR spectroscopy were employed to characterize its self-assembly
      process and the resultant assemblies. The vesicles could encapsulate calcein
      within their interiors under neutral conditions and release it in response to a
      decrease in pH. The microtubes, which have primary amine groups on their
      surfaces, could adsorb TNT through donor-acceptor interactions.

PMID- 22967169
TI  - HHS Releases New Strategy for Emergency Medical Countermeasures Enterprise.

PMID- 22967171
TI  - Resonance frequency analysis assessment of implants placed with a simultaneous or
      a delayed approach in grafted and nongrafted sinus sites: a 12-month clinical
      study.
AB  - BACKGROUND: Implant stability is one of the key factors for a successful
      osseointegration. At present, several techniques are available to regenerate bone
      tissue, but it is not clear whether implants placed in grafted bone are as stable
      as implants in native bone over time. PURPOSE: The aim of the present study was
      to compare, by means of resonance frequency analysis (RFA), the stability of
      implants placed in sinus-grafted and -nongrafted sites during 12-month follow-up.
      METHODS: Twenty-five patients received a total of 38 implants. Nineteen implants
      were placed in maxillary native bone (group A) and 19 implants following
      maxillary sinus floor augmentation using anorganic bovine bone and autogenous
      bone (group B) in a 50:50 ratio. Group B was divided into groups B1 and B2
      depending on the timing of implant insertion, that is, B1 simultaneously and B2 6
      months after sinus lift. The implants were inserted according to a two-stage
      procedure. RFA values were collected at baseline, 6 and 12 months after implant
      placement. RESULTS: Between the tested groups, no statistically significant
      difference was found in RFA values of implants placed in sinus-grafted and 
      nongrafted sites after the surgery as well as at 6 and 12 months, while a
      significant difference was recorded in group B1 (p = .0297) when RFA values were
      compared over time. CONCLUSIONS: The results of the present study suggest that
      regenerated bone can offer good stability for dental implants.

PMID- 22967170
TI  - A high-density genetic map of Arachis duranensis, a diploid ancestor of
      cultivated peanut.
AB  - BACKGROUND: Cultivated peanut (Arachis hypogaea) is an allotetraploid species
      whose ancestral genomes are most likely derived from the A-genome species, A.
      duranensis, and the B-genome species, A. ipaensis. The very recent (several
      millennia) evolutionary origin of A. hypogaea has imposed a bottleneck for
      allelic and phenotypic diversity within the cultigen. However, wild diploid
      relatives are a rich source of alleles that could be used for crop improvement
      and their simpler genomes can be more easily analyzed while providing insight
      into the structure of the allotetraploid peanut genome. The objective of this
      research was to establish a high-density genetic map of the diploid species A.
      duranensis based on de novo generated EST databases. Arachis duranensis was
      chosen for mapping because it is the A-genome progenitor of cultivated peanut and
      also in order to circumvent the confounding effects of gene duplication
      associated with allopolyploidy in A. hypogaea. RESULTS: More than one million
      expressed sequence tag (EST) sequences generated from normalized cDNA libraries
      of A. duranensis were assembled into 81,116 unique transcripts. Mining this
      dataset, 1236 EST-SNP markers were developed between two A. duranensis
      accessions, PI 475887 and Grif 15036. An additional 300 SNP markers also were
      developed from genomic sequences representing conserved legume orthologs. Of the
      1536 SNP markers, 1054 were placed on a genetic map. In addition, 598 EST-SSR
      markers identified in A. hypogaea assemblies were included in the map along with
      37 disease resistance gene candidate (RGC) and 35 other previously published
      markers. In total, 1724 markers spanning 1081.3 cM over 10 linkage groups were
      mapped. Gene sequences that provided mapped markers were annotated using
      similarity searches in three different databases, and gene ontology descriptions
      were determined using the Medicago Gene Atlas and TAIR databases. Synteny
      analysis between A. duranensis, Medicago and Glycine revealed significant
      stretches of conserved gene clusters spread across the peanut genome. A higher
      level of colinearity was detected between A. duranensis and Glycine than with
      Medicago. CONCLUSIONS: The first high-density, gene-based linkage map for A.
      duranensis was generated that can serve as a reference map for both wild and
      cultivated Arachis species. The markers developed here are valuable resources for
      the peanut, and more broadly, to the legume research community. The A-genome map
      will have utility for fine mapping in other peanut species and has already had
      application for mapping a nematode resistance gene that was introgressed into A.
      hypogaea from A. cardenasii.

PMID- 22967172
TI  - Genomic and phenotypic architecture of a spruce hybrid zone (Picea sitchensis *
      P. glauca).
AB  - Interspecific hybridization may enhance the capacity of populations to adapt to
      changing environments, and has practical implications for reforestation. We use
      genome-wide estimates of admixture and phenotypic traits for trees in a common
      garden to examine the extent and direction of gene flow across a Picea hybrid
      zone, testing assumptions of the bounded hybrid superiority and tension zone
      models of hybrid zone maintenance. Seeds were collected from the ecological
      transition zone spanning from maritime to continental climates across the Picea
      sitchensis-P. glauca contact zone, and 721 trees were planted in a common garden
      experiment within the hybrid zone. Individuals were genotyped using a panel of
      384 candidate-gene single nucleotide polymorphisms (SNPs) putatively associated
      with adaptive traits in Picea, and phenotyped at age ten for height and autumn
      cold hardiness. Low interspecific heterozygosity in hybrids indicated that
      intrinsic reproductive barriers were too weak to prevent widespread
      recombination, although introgression appeared asymmetric with P. sitchensis
      dominating the zone. Whereas marker-based hybrid index was strongly correlated
      with climate and geography, phenotypic traits exhibited weak or no significant
      clines. Our results indicated that exogenous selection appeared to play a strong
      role in the distribution and structure of this hybrid zone, indicative of an
      environmentally determined bounded hybrid superiority model of hybrid zone
      maintenance, although endogenous mechanisms could not be ruled out. This study
      provides insight into the mechanisms underlying adaptation across ecologically
      transitional hybrid zones that will ultimately provide an additional tool in
      managing these economically important tree species.

PMID- 22967174
TI  - Left-sided pulmonary venous pathway obstruction after Mustard operation.
AB  - OBJECTIVE: Pulmonary venous pathway obstruction (PVPO) is a serious complication
      of the atrial switch procedure for transposition of the great arteries (TGA).
      Redistribution of pulmonary arterial blood flow may make conventional
      echocardiographic measures of unilateral PVPO difficult to interpret. Previous
      studies have demonstrated altered arterial flow patterns using phase-contrast
      magnetic resonance imaging (PC-MRI). The purpose of this study was to investigate
      arterial flow patterns in the setting of unilateral PVPO following the Mustard
      operation. METHODS: We retrospectively reviewed the arterial flow patterns of 12
      patients undergoing magnetic resonance imaging between 2006 and 2011 who had had
      the Mustard operation. RESULTS: Three patients had left PVPO and all showed >65%
      flow distributed to the right pulmonary artery (RPA). One had severe obstruction
      and was the only one to show significant continuous diastolic forward flow in the
      RPA or diastolic flow reversal in the left pulmonary artery. CONCLUSION: RPA/left
      pulmonary artery flow ratio appears to be a sensitive marker for PVPO. In the
      absence of pulmonary regurgitation, reversed diastolic flow in the ipsilateral
      and continuous in the contralateral pulmonary artery appears specific for severe
      obstruction. Branch pulmonary artery phase-contrast magnetic resonance imaging
      (PC-MRI) should be performed routinely for patients who have had an atrial switch
      for transposition of the great arteries.

PMID- 22967175
TI  - Brazilin induces apoptosis and G2/M arrest via inactivation of histone
      deacetylase in multiple myeloma U266 cells.
AB  - Although brazilin [7,11b-dihydrobenz(b)indeno[1,2-d]pyran-3,6a,9,10(6H)-tetrol]
      isolated from  Caesalpinia sappan  was known to have various biological
      activities, including anti-inflammation, antibacteria, and antiplatelet
      aggregation, there is no report yet on its anticancer activity. In the present
      study, the anticancer mechanism of brazilin was elucidated in human multiple
      myeloma U266 cells. We found that brazilin significantly inhibited the activity
      of histone deacetylases (HDACs), transcription factors involved in the regulation
      of apoptosis and cell cycle arrest in U266 cells. Consistently, brazilin enhanced
      acetylation of histone H3 at Lys 23, indicating activation of histone
      acetyltransferase (HAT), and also suppressed the expressions of HDAC1 and HDAC2
      at both protein and mRNA levels. Additionally, brazilin significantly increased
      the number of sub-G1 cell population and terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL)-positive cells undergoing apoptosis and also
      activated caspase-3 and regulated the expression of Bcl-2 family proteins,
      including Bax, Bcl-x(L), and Bcl-2 in U266 cells, indicating that brazilin
      induces apoptosis through the mitochondria-dependent pathway. Interestingly, cell
      cycle analysis revealed that brazilin induced G2/M phase arrest along with
      apoptosis induction. Consistently, brazilin attenuated the expression of cyclin
      dependent kinases (CDKs), such as cyclin D1, cyclin B1, and cyclin E, and also
      activated p21 and p27 in U266 cells. Furthermore, HAT inhibitor anacardic acid
      reversed activation of acetyl-histone H3 and cleavage of PARP induced by
      brazilin, while pan-caspase inhibitor Z-VAD-FMK001 did not affect the expression
      of HDAC induced by brazilin that brazilin mediates apoptosis via inactivation of
      HDAC in U266 cells. Notably, brazilin significantly potentiated the cytotoxic
      effect of standard chemotherapeutic agents, such as bortezomib or doxorubicin, in
      U266 cells. When our findings are taken together, they suggest that brazilin has
      potential as a chemotherapeutic agent alone or in combination with an anticancer
      agent for multiple myeloma treatment.

PMID- 22967176
TI  - DNA base dimers are stabilized by hydrogen-bonding interactions including non
      Watson-Crick pairing near graphite surfaces.
AB  - Single- and double-stranded DNA are increasingly being paired with surfaces and
      nanoparticles for numerous applications, such as sensing, imaging, and drug
      delivery. Unlike the majority of DNA structures in bulk that are stabilized by
      canonical Watson-Crick pairing between Ade-Thy and Gua-Cyt, those adsorbed on
      surfaces are often stabilized by noncanonical base pairing, quartet formation,
      and base-surface stacking. Not much is known about these kinds of interactions.
      To build an understanding of the role of non-Watson-Crick pairing on DNA behavior
      near surfaces, one requires basic information on DNA base pair stacking and
      hydrogen-bonding interactions. All-atom molecular simulations of DNA bases in two
      cases--in bulk water and strongly adsorbed on a graphite surface--are conducted
      to study the relative strengths of stacking and hydrogen bond interactions for
      each of the 10 possible combinations of base pairs. The key information obtained
      from these simulations is the free energy as a function of distance between two
      bases in a pair. We find that stacking interactions exert the dominant influence
      on the stability of DNA base pairs in bulk water as expected. The strength of
      stability for these stacking interactions is found to decrease in the order Gua
      Gua > Ade-Gua > Ade-Ade > Gua-Thy > Gua-Cyt > Ade-Thy > Ade-Cyt > Thy-Thy > Cyt
      Thy > Cyt-Cyt. On the other hand, mutual interactions of surface-adsorbed base
      pairs are stabilized mostly by hydrogen-bonding interactions in the order Gua-Cyt
      > Ade-Gua > Ade-Thy > Ade-Ade > Cyt-Thy > Gua-Gua > Cyt-Cyt > Ade-Cyt > Thy-Thy >
      Gua-Thy. Interestingly, several non-Watson-Crick base pairings, which are
      commonly ignored, have similar stabilization free energies due to interbase
      hydrogen bonding as Watson-Crick pairs. This clearly highlights the importance of
      non-Watson-Crick base pairing in the development of secondary structures of
      oligonucleotides near surfaces.

PMID- 22967177
TI  - Temperature control during regeneration of activated carbon fiber cloth with
      resistance-feedback.
AB  - Electrothermal swing adsorption (ESA) of organic compounds from gas streams with
      activated carbon fiber cloth (ACFC) reduces emissions to the atmosphere and
      recovers feedstock for reuse. Local temperature measurement (e.g., with a
      thermocouple) is typically used to monitor/control adsorbent regeneration cycles.
      Remote electrical resistance measurement is evaluated here as an alternative to
      local temperature measurement. ACFC resistance that was modeled based on its
      physical properties was within 10.5% of the measured resistance values during
      electrothermal heating. Resistance control was developed based on this measured
      relationship and used to control temperature to within 2.3% of regeneration set
      point temperatures. Isobutane-laden adsorbent was then heated with resistance
      control. After 2 min of heating, the temperature of the adsorbent with isobutane
      was 13% less than the adsorbent without isobutane. This difference decreased to
      2.1% after 9 min of heating, showing desorption of isobutane. An ACFC cartridge
      was also heated to 175  degrees C for 900 cycles with its resistance and
      adsorption capacity values remaining within 3% and 2%, respectively. This new
      method to control regeneration power application based on rapid sensing of the
      adsorbent's resistance removes the need for direct-contact temperature sensors
      providing a simple, cost-efficient, and long-term regeneration technique for ESA
      systems.

PMID- 22967178
TI  - Constituents from Salvia species and their biological activities.

PMID- 22967179
TI  - Robot-assisted laparoscopic partial nephrectomy for recurrent renal-cell
      carcinoma in patients previously treated with nephron-sparing surgery.
AB  - BACKGROUND AND PURPOSE: With the advent of robotics, it may be more feasible to
      offer minimally invasive nerve-sparing surgery (NSS), in the form of partial
      nephrectomy (PN), for patients with metachronous recurrence in the ipsilateral
      kidney after previous NSS. We studied the outcomes of patients undergoing robot
      assisted laparoscopic partial nephrectomy (RAPN) after previous ipsilateral open
      or laparoscopic NSS for renal-cell carcinoma. METHODS: In this Institutional
      Review Board approved study, a prospectively maintained PN database was reviewed.
      Of 230 RAPNs performed between 2003 and 2011, five patients underwent RAPN after
      previous ipsilateral NSS. RESULTS: The mean age was 64.2 years, and time between
      the first and second surgery was 27 months (range 9-60 mos). All patients were
      men and previously had open (n=4) or laparoscopic (n=1) NSS for clear-cell (n=2),
      papillary (n=2), and other (n=1) pathology. Average follow-up was 15.6 months
      (range 8-21 mos). There were no conversions to open surgery or radical
      nephrectomy. Total and selective arterial clamping were performed in two and two
      cases, respectively. One RAPN was performed off-clamp. Mean warm ischemia time
      was 14 minutes (range 0-32 min), and mean blood loss was 220 mL (range 50-400
      mL). Average length of stay was 1.4 days (range 1-2 days) with no perioperative
      complications. The glomerular filtration rate decreased by a mean of 10%. There
      were no recurrences detected on cross-sectional imaging at the most recent follow
      up. CONCLUSION: RAPN after previous open or laparoscopic PN is safe and
      efficacious. It offers satisfactory intermediate functional and oncologic
      outcomes with minimal morbidity.

PMID- 22967180
TI  - Construction of a rhythm transfer system that mimics the cellular clock.
AB  - Creation of an artificial oscillating gene expression system is one of the most
      challenging issues in synthetic biology. Here, we constructed a simple system to
      manipulate gene expression patterns to be circadian, reflecting the intrinsic
      cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc
      finger-type DNA binding domain. Circadian rhythmic gene expression was induced
      only when the target gene contained zinc finger-binding sequences. To our
      knowledge, this simple approach is the first to manipulate gene expression
      patterns into circadian rhythms and would be applicable to various endogenous
      genes.

PMID- 22967182
TI  - Toward a predictive model of Alzheimer's disease progression using capillary
      electrophoresis-mass spectrometry metabolomics.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia with an estimated
      worldwide prevalence of over 30 million people, and its incidence is expected to
      increase dramatically with an increasing elderly population. Up until now,
      cerebrospinal fluid (CSF) has been the preferred sample to investigate central
      nervous system (CNS) disorders since its composition is directly related to
      metabolite production in the brain. In this work, a nontargeted metabolomic
      approach based on capillary electrophoresis-mass spectrometry (CE-MS) is
      developed to examine metabolic differences in CSF samples from subjects with
      different cognitive status related to AD progression. To do this, CSF samples
      from 85 subjects were obtained from patients with (i) subjective cognitive
      impairment (SCI, i.e. control group), (ii) mild cognitive impairment (MCI) which
      remained stable after a follow-up period of 2 years, (iii) MCI which progressed
      to AD within a 2-year time after the initial MCI diagnostic and, (iv) diagnosed
      AD. A prediction model for AD progression using multivariate statistical analysis
      based on CE-MS metabolomics of CSF samples was obtained using 73 CSF samples.
      Using our model, we were able to correctly classify 97-100% of the samples in the
      diagnostic groups. The prediction power was confirmed in a blind small test set
      of 12 CSF samples, reaching a 83% of diagnostic accuracy. The obtained predictive
      values were higher than those reported with classical CSF AD biomarkers (Abeta42
      and tau) but need to be confirmed in larger samples cohorts. Choline,
      dimethylarginine, arginine, valine, proline, serine, histidine, creatine,
      carnitine, and suberylglycine were identified as possible disease progression
      biomarkers. Our results suggest that CE-MS metabolomics of CSF samples can be a
      useful tool to predict AD progression.

PMID- 22967181
TI  - Dietary vegetable oils do not alter the intestine transcriptome of gilthead sea
      bream (Sparus aurata), but modulate the transcriptomic response to infection with
      Enteromyxum leei.
AB  - BACKGROUND: Studies conducted with gilthead sea bream (Sparus aurata L.) have
      determined the maximum dietary replacement of fish meal and oil without
      compromising growth or product quality. The present study aimed to analyze the
      effect of the nutritional background on fish health and fish fed plant protein
      based diets with fish oil (FO diet) or a blend of vegetable oils (66VO diet) were
      exposed for 102 days to the intestinal myxosporean parasite Enteromyxum leei, and
      the intestine transcriptome was analyzed with a customized oligo-microarray of
      7,500 annotated genes. RESULTS: Infection prevalence was high and similar in the
      two diet groups, but the outcome of the disease was more pronounced in fish fed
      the 66VO diet. No differences were found in the transcriptome of both diet
      control groups, whereas the number of differentially expressed genes in infected
      groups was considerable. K-means clustering of these differentially expressed
      genes identified four expression patterns that reflected the progression of the
      disease with the magnitude of the fold-change being higher in infected 66VO fish.
      A positive correlation was found between the time of infection and the magnitude
      of the transcriptional change within the 66VO group, being higher in early
      infected animals. Within this diet group, a strong up-regulation of many
      components of the immune specific response was evidenced, whereas other genes
      related to complement response and xenobiotic metabolism were down-regulated.
      CONCLUSIONS: The high replacement of fish oil by vegetable oils in practical fish
      feeds did not modify the intestine transcriptome of gilthead sea bream, but
      important changes were apparent when fish were exposed to the myxosporean E.
      leei. The detected changes were mostly a consequence rather than a cause of the
      different disease progression in the two diet groups. Hence, the developed
      microarray constitutes an excellent diagnostic tool to address changes associated
      with the action of intestinal pathogens, but lacks a prognostic value to predict
      in advance the different susceptibility of growing fish to the current pathogen.

PMID- 22967183
TI  - DNA methyltransferase 1 (Dnmt1) mutation affects Snrpn imprinting in the mouse
      male germ line.
AB  - DNA methylation and DNA methyltransferases are essential for spermatogenesis.
      Mutations in the DNA methyltransferase Dnmt1 gene exert a paternal effect on
      epigenetic states and phenotypes of offspring, suggesting that DNMT1 is important
      for the epigenetic remodeling of the genome that takes place during
      spermatogenesis. However, the specific role of DNMT1 in spermatogenesis and the
      establishment of genomic imprints in the male germ line remains elusive. To
      further characterize the effect of DNMT1 deficiency on the resetting of
      methylation imprints during spermatogenesis, we analyzed the methylation profiles
      of imprinted regions in the spermatozoa of mice that were heterozygous for a
      Dnmt1 loss-of-function mutation. The mutation did not affect the H19 or IG
      differentially methylated regions (DMRs) that are usually highly methylated but
      led to a partial hypermethylation of the Snrpn DMR, a region that should normally
      be unmethylated in mature spermatozoa. This defect does not appear in mouse
      models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific
      for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or
      maintenance in the male germ line.

PMID- 22967184
TI  - Bologna in Medicine Anno 2012: experiences of European medical schools that
      implemented a Bologna two-cycle curriculum--an AMEE-MEDINE2 survey.
AB  - BACKGROUND: The 1999 Bologna Agreement implies a European harmonization of higher
      education using three cycles: bachelor and master before doctorate. Undergraduate
      medical programmes were restructured in only seven of the 47 countries. AIM:
      Given the debate about a two-cycle system in undergraduate medical education,
      providing an overview of experiences in medical schools that applied this
      structure was the purpose of this investigation. METHODS: In 2009, an AMEE
      MEDINE2 survey was carried out among all the 32 medical schools that applied the
      two-cycle system in medicine. At the end of 2011, a member-check validation using
      a draft manuscript was carried out to complete an accurate up-to-date impression.
      RESULTS: All the 32 schools responded initially; 26 schools responded to the
      second round. All schools had implemented the two-cycle system (all but one in a
      3 + 3 year model) with hardly any problems. All reported smaller or larger
      curriculum improvements, often triggered, but not caused, by the two-cycle
      system. No school reported that introducing the system interfered with any
      desired curriculum development, particularly horizontal or vertical integration.
      CONCLUSION: In 32 of the 442 medical schools in Bologna signatory countries,
      introducing a two-cycle model for basic medical education was successfully
      completed. However, harmonization of medical training in Europe requires further
      international collaboration.

PMID- 22967185
TI  - Cultivating grassroots IPE: the Dalhousie University experience.
AB  - A bottom-up and menu-based approach to embedding interprofessional education
      (IPE) into the curricula of more than 20 health profession programs at Dalhousie
      University is described. In addition to adopting an IPE graduation requirement
      and a common time for IPE activities, progress appears to have been facilitated
      by placing responsibility directly with the schools that own the curricula rather
      than with a central office for IPE.

PMID- 22967187
TI  - Pregabalin treatment for peripheral neuropathic pain: a review of safety data
      from randomized controlled trials conducted in Japan and in the west.
AB  - Two well-studied conditions of peripheral neuropathic pain are postherpetic
      neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Several
      pregabalin trials for peripheral neuropathic pain have been conducted in the
      West, but limited data are available for Japan. As ethnicity may influence health
      risks, differences may be evident in safety data from pregabalin trials in Japan
      and in the West. The objectives of this review were to compare large pooled
      safety data from randomized controlled trials evaluating pregabalin for the
      treatment of PHN or DPN in the West with data from two (one PHN, N = 371; one
      DPN, N = 314) similar trials in Japan. Longer-term safety data from Japanese open
      label extension studies were also reviewed in these neuropathic pain populations.
      Published and unpublished Pfizer-supported pregabalin trials were identified and
      sourced from internal Pfizer records. A PubMed search to check for inclusiveness
      was conducted on 2 November 2011 using the following criteria: 'diabetic
      peripheral neuropathy' OR 'postherpetic neuralgia' OR 'neuropathic pain' AND
      'pregabalin', with limits set for clinical and randomized controlled trials
      published in English. Five PHN trials (N = 1250) and nine DPN trials (N = 2554)
      were identified as suitable for inclusion based on methodological comparability.
      Descriptive safety data from the original trials were reviewed and the most
      commonly reported adverse events (AEs; dizziness, somnolence, peripheral oedema
      and weight gain) were identified to be of primary interest. The majority of AEs
      were of mild to moderate severity in Japanese and Western populations. The most
      commonly reported AE data (all-causality) with pregabalin (regardless of dose) in
      Japan (dizziness: PHN = 31.1%; DPN = 24.6%, and somnolence: PHN = 28.6%; DPN =
      25.7%) were compared with pooled data from the Western trials (dizziness: PHN =
      24.9%; DPN = 23.0%, and somnolence: PHN = 15.1%; DPN = 13.4%). Further assessment
      of these pooled AE (all-causality) data showed that dizziness and somnolence
      appeared early in the course of pregabalin treatment, but resolved before the end
      of the treatment in the majority of PHN and DPN patients (maximum duration of
      trials was 13 weeks). The slightly higher incidence of dizziness and somnolence
      in the two Japanese trials than that seen in the Western trials may reflect an
      increased exposure to pregabalin per fixed dose due to the lower mean bodyweight
      of the Japanese versus Western populations (on a mg/kg basis). However, of the
      participants who experienced these AEs (all-causality), the proportion who
      withdrew from the trials in Japan (dizziness: PHN = 23.5%; DPN = 18.2%, and
      somnolence: PHN = 10.3%; DPN = 10.9%) were comparable with the proportion who
      withdrew from trials in the West (dizziness: PHN = 16.0%; DPN = 29.3%, and
      somnolence: PHN = 19.4%; DPN = 34.2%). In Japan, 12.5% (PHN) and 15.1% (DPN) of
      patients experienced peripheral oedema as an AE (all-causality) compared with
      8.8% (PHN) and 10.3% (DPN) in the West. Weight gain as an AE (all-causality) was
      experienced in 11.7% (PHN) and 13.4% (DPN) of patients in Japan compared with
      3.8% (PHN) and 7.0% (DPN) in the West, but stabilized with continued treatment.
      Despite the lower mean bodyweight in Japanese versus Western patients, the PHN
      and DPN patients in Japan had stable blood glucose and HbA(1c) levels throughout
      the trials. The results of this review indicate safety outcomes in pregabalin
      trials are comparable between patients in Japan and those in the West. While
      managing peripheral neuropathic pain with pregabalin treatment, all patients
      should be observed closely for the incidence of dizziness and somnolence,
      especially at the beginning of treatment. These patients should also be monitored
      for evidence of peripheral oedema and weight gain during stable treatment,
      regardless of the source of neuropathic pain.

PMID- 22967188
TI  - Comparing tolerability of olanzapine in schizophrenia and affective disorders: a
      meta-analysis.
AB  - BACKGROUND: Olanzapine is prescribed for a number of psychiatric disorders,
      including schizophrenia, bipolar mania, and unipolar and bipolar depression.
      Olanzapine treatment is associated with tolerability issues such as metabolic
      adverse effects (e.g. weight gain, increase in blood glucose, triglycerides and
      total cholesterol levels), extrapyramidal symptoms [EPS] (e.g. parkinsonism,
      akathisia, tardive dyskinesia) and sedative adverse effects. Metabolic issues
      lead to some long-term consequences, which include cardiovascular diseases (CVD)
      and type 2 diabetes mellitus, and these complications cause high rates of
      mortality and morbidity among patients with severe mental illnesses. The expanded
      indications of olanzapine in psychiatry suggest a need to investigate whether
      there is a difference in the incidence and severity of adverse effects related to
      category diagnosis. Are the adverse effects expressed differently according to
      phenotype? Unfortunately, there are no reported studies that investigated these
      differences in adverse effects associated with olanzapine treatment in
      psychiatric patients with different phenotypes. OBJECTIVE: The aim of the present
      meta-analysis is to separately examine olanzapine-induced cardiometabolic adverse
      effects and EPS in patients with schizophrenia and affective disorders. DATA
      SOURCES: A search of computerized literature databases PsycINFO (1967-2010),
      PubMed (MEDLINE), EMBASE (1980-2010) and the clinicaltrials.gov website for
      randomized clinical trials was conducted. A manual search of reference lists of
      published review articles was carried out to gather further data. STUDY
      SELECTION: Randomized controlled trials were included in our study if (i) they
      assessed olanzapine adverse effects (metabolic or extrapyramidal) in adult
      patients with schizophrenia or affective disorders; and (ii) they administered
      oral olanzapine as monotherapy during study. DATA EXTRACTION: Two reviewers
      independently screened abstracts for choosing articles and one reviewer extracted
      relevant data on the basis of predetermined exclusion and inclusion criteria. It
      should be mentioned that for the affective disorders group we could only find
      articles related to bipolar disorder. DATA SYNTHESIS: Thirty-three studies (4831
      patients) that address olanzapine monotherapy treatment of adults with
      schizophrenia or bipolar disorder were included in the analysis. The primary
      outcomes were metabolic adverse effects (changes in weight, blood glucose, low
      density lipoprotein, total cholesterol and triglyceride levels). The secondary
      outcomes of our study were assessing the incidence of some EPS (parkinsonism,
      akathisia and use of antiparkinson medication). The tolerability outcomes were
      calculated separately for the schizophrenia and bipolar disorder groups and were
      combined in a meta-analysis. Tolerability outcomes show that olanzapine
      contributes to weight gain and elevates blood triglycerides, glucose and total
      cholesterol levels in both schizophrenia and bipolar disorder patients. However,
      olanzapine treatment produced significantly more weight gain in schizophrenia
      patients than in bipolar disorder patients. In addition, increases in blood
      glucose, total cholesterol and triglyceride levels were higher in the
      schizophrenia group compared with the bipolar disorder group, even though these
      differences were not statistically significant. Based on our results, the
      incidence of parkinsonism was significantly higher in the schizophrenia group
      than in the bipolar disorder group. Subgroup analysis and logistic regression
      were used to assess the influence of treatment duration, dose, industry
      sponsorship, age and sex ratio on tolerability outcome. CONCLUSIONS: Our results
      suggest that schizophrenia patients may be more vulnerable to olanzapine-induced
      weight gain. The findings may be explained by considering the fact that in
      addition to genetic disposition for metabolic syndrome in schizophrenia patients,
      they have an especially high incidence of lifestyle risk factors for CVD, such as
      poor diet, lack of exercise, stress and smoking. It might be that an
      antipsychotic induces severity of adverse effect according to the phenotype.

PMID- 22967189
TI  - First French experience of ADR reporting by patients after a mass immunization
      campaign with Influenza A (H1N1) pandemic vaccines: a comparison of reports
      submitted by patients and healthcare professionals.
AB  - BACKGROUND: Available data concerning the contribution of patient adverse drug
      reaction (ADR) reporting in practice are scarce. Few studies have compared
      patients' reports with reports from healthcare professionals (HCPs). During the
      2009-10 mass immunization campaign with A (H1N1)v2009 pandemic influenza
      vaccines, a reinforced pharmacovigilance plan was introduced in France according
      to European Medicines Agency recommendations. For the first time, patients were
      offered the opportunity to report suspected ADRs to pandemic vaccines directly to
      regional pharmacovigilance centres. OBJECTIVE: The aim of the study was to
      compare the characteristics of patient and HCP ADR reports in order to assess the
      qualitative and quantitative contribution of patient reporting to the French
      Pharmacovigilance System. METHODS: All spontaneous ADRs registered into the
      French Pharmacovigilance Database from 21 October 2009 to 15 June 2010, in which
      either one of the most frequently administered pandemic vaccines (i.e. Panenza(r)
      or Pandemrix(r)) was involved, were analysed. ADRs were classified as 'serious',
      'medically serious' and 'non-serious'. This study focused on 'serious' and
      'medically serious' ADRs. An ADR was ranked as 'medically serious' when it
      required medical intervention or hospitalization within less than 24 hours. In
      each level of seriousness, frequency of 'unlabelled' ADRs, ADRs of 'special
      interest', imputability scores and category of ADRs according to Medical
      Dictionary for Regulatory Activitives (MedDRA(r)) primary System Organ Class were
      compared between patient and professional reports. RESULTS: Among the 4746
      reports received during the study period, 1006 (21.2%) originated from patients.
      HCPs reported significantly more 'medically serious' or 'serious' ADRs than
      patients (15.1% [565/3740] vs 8.4% [85/1006], respectively; p < 0.001). No
      difference was found in 'unlabelled, serious' ADRs between patients and HCPs
      (56.5% [n = 13] vs 56.7% [n = 136], respectively). CONCLUSIONS: In this first
      French experience of formal patient participation to ADR reporting, patient
      contribution to the total number of ADRs reached 21.2%. This study revealed no
      major qualitative difference between patient and HCP reports. ADR profiles
      reported by patients appeared to be consistent with those from professionals.
      Further investigations are necessary to assess the intrinsic quality of
      notification forms coming from non-professional reporters. However, this study is
      of particular interest in the context of publication of the first governmental
      decree that will formally integrate patient participation to the current French
      ADR reporting scheme.

PMID- 22967190
TI  - Effect of competition bias in safety signal generation: analysis of a research
      database of spontaneous reports in France.
AB  - BACKGROUND: Automated disproportionality analysis of spontaneous reporting is
      increasingly used routinely. It can theoretically be influenced by a competition
      bias for signal detection owing to the presence of reports related to well
      established drug-event associations. OBJECTIVE: The aim of the study was to
      explore the effects of competition bias on safety signals generated from a large
      spontaneous reporting research database. METHODS: Using the case/non-case
      approach in the French spontaneous reporting research database, which includes
      data of reporting in France from January 1986 to December 2001, the effects of
      the competition bias were explored by generating safety signals associated with
      six events of interest (gastric and oesophageal haemorrhages, central nervous
      system haemorrhage and cerebrovascular accidents, ischaemic coronary disorders,
      migraine headaches, muscle pains, and hepatic enzymes and function abnormalities)
      before and after removing from the database reports relating to drugs known to be
      strongly associated with these events, whether they constituted cases or non
      cases. As this study was performed on a closed database (last data entered 31
      December 2001), potential signals unmasked by removal were considered as real
      signals if no or only incomplete knowledge about the association was available
      from the literature before 1 January 2002. RESULTS: For gastric and oesophageal
      haemorrhages, after removing reports involving antithrombotic agents or NSAIDs,
      three potential signals were unmasked (prednisone, rivastigmine and
      isotretinoin). For central nervous system haemorrhage and cerebrovascular
      accidents, after removing reports involving antithrombotic agents, three
      potential signals were unmasked (ethinylestradiol, interferon-alpha-2B and
      methylprednisolone). For ischaemic coronary disorders, after removing reports
      involving anthracyclines, bleomycine, anti-HIV drugs or triptans, one potential
      signal was unmasked (ondansetron). For migraine headaches, after removing reports
      involving nitrates, calcium channel blockers, opioid analgesics or intravenous
      immunoglobulins, six potential signals were unmasked (ammonium chloride,
      leflunomide, milnacipran, montelukast, proguanil and pyridostigmine). For muscle
      pains, after removing reports involving statins or fibrates, seven potential
      signals were unmasked (hydroxychloroquine, lactulose, levodopa in combination
      with dopadecarboxylase inhibitor, nevirapine, nomegestrol, ritonavir and
      stavudine). Finally, for hepatic enzymes and function abnormalities, after
      removing reports involving NSAIDs, anilides, antituberculosis drugs,
      antiepileptics, ketoconazole, tacrine, or amineptine, two potential signals were
      unmasked (caffeine, metformin). Of all these unmasked potential signals, ten
      appeared non/incompletely documented as at 1 January 2002 and were considered as
      real signals, with three of these later being confirmed by the literature and
      finally considered as true positives (isotretinoin, methylprednisolone and
      milnacipran). CONCLUSION: This study confirms that a competition bias can occur
      when performing safety signal generation in spontaneous reporting databases. The
      minimization of this bias could lead to previously masked signals being revealed.

PMID- 22967192
TI  - A three-dimensional axis for the study of femoral neck orientation.
AB  - A common problem in the quantification of the orientation of the femoral neck is
      the difficulty to determine its true axis; however, this axis is typically
      estimated visually only. Moreover, the orientation of the femoral neck is
      commonly analysed using angles that are dependent on anatomical planes of
      reference and only quantify the orientation in two dimensions. The purpose of
      this study is to establish a method to determine the three-dimensional
      orientation of the femoral neck using a three-dimensional model. An accurate
      determination of the femoral neck axis requires a reconsideration of the complex
      architecture of the proximal femur. The morphology of the femoral neck results
      from both the medial and arcuate trabecular systems, and the asymmetry of the
      cortical bone. Given these considerations, two alternative models, in addition to
      the cylindrical one frequently assumed, were tested. The surface geometry of the
      femoral neck was subsequently used to fit one cylinder, two cylinders and
      successive cross-sectional ellipses. The model based on successive ellipses
      provided a significantly smaller average deviation than the two other models (P <
      0.001) and reduced the observer-induced measurement error. Comparisons with
      traditional measurements and analyses on a sample of 91 femora were also
      performed to assess the validity of the model based on successive ellipses. This
      study provides a semi-automatic and accurate method for the determination of the
      functional three-dimensional femoral neck orientation avoiding the use of a
      reference plane. This innovative method has important implications for future
      studies that aim to document and understand the change in the orientation of the
      femoral neck associated with the acquisition of a bipedal gait in humans.
      Moreover, the precise determination of the three-dimensional orientation has
      implications in current research involved in developing clinical applications in
      diagnosis, hip surgery and rehabilitation.

PMID- 22967193
TI  - On the meaning and use of the risk appetite concept.
AB  - The risk appetite concept has been given considerable attention recently in
      enterprise risk management contexts. A number of definitions exist, most with a
      link to risk acceptability, but also values and goals. The usefulness of the
      concept is, however, disputed; some authors argue that we can in fact do better
      without it. In this article, we provide a thorough discussion of what the risk
      appetite concept is actually trying to express and how it best can be used in the
      relevant decision making. The main purposes of the article are (i) to argue that
      the risk appetite concept, suitably interpreted, has a role to play in risk
      management, (ii) to show that the risk appetite concept is well supported by some
      types of risk perspectives and not by others, and (iii) to show how the risk
      appetite concept is linked to other related concepts, such as risk seeking and
      risk acceptability. The risk perspectives studied range from expected value and
      probability based definitions of risk to views on risk, that are founded on
      uncertainties.

PMID- 22967194
TI  - Exploring the role of asexual multiplication in poplar rust epidemics: impact on
      diversity and genetic structure.
AB  - Fungal plant pathogens, especially rust fungi (Pucciniales), are well known for
      their complex life cycles, which include phases of sexual and asexual
      reproduction. The effect of asexual multiplication on population genetic
      diversity has been investigated in the poplar rust fungus Melampsora larici
      populina using a nested hierarchical sampling scheme. Four hierarchical levels
      were considered: leaf, twig, tree and site. Both cultivated and wild poplar
      stands were sampled at two time points at the start and end of rust epidemics. A
      total of 641 fungal isolates was analysed using nine microsatellite markers. This
      study revealed that the genetic signature of asexual multiplication in the wild
      poplar stand was seen only at lower hierarchical levels (leaf and twig).
      Moreover, we observed an erosion of clonal structure through time, with an
      increase in both gene and genotypic diversity. New genotypes contributed to host
      infection over time, which demonstrates the importance of allo-infection in the
      epidemic process in this host-pathogen system. Compared with the wild stands, the
      nearly lack of detection of clonal structure in the cultivated stands reflects
      the higher infection level on cultivated poplars. More generally, this genetic
      analysis illustrates the utility of population genetics approach for elucidating
      the proportion of asexual reproduction in the multiplication of isolates during
      an epidemic, and for proper quantification of asexual dispersal in plant
      pathogens.

PMID- 22967196
TI  - Intensive care registries and the evolution of the concept of 'quality of care' -
      reflections from the 10-year anniversary symposium of the Swedish Intensive Care
      Registry.

PMID- 22967195
TI  - Explaining the effects of a point-of-purchase nutrition-information intervention
      in university canteens: a structural equation modelling analysis.
AB  - BACKGROUND: The importance of canteen meals in the diet of many university
      students makes the provision of simple point-of-purchase (POP) nutrition
      information in university canteens a potentially effective way to promote
      healthier diets in an important group of young adults. However, modifications to
      environments such as the posting of POP nutrition information in canteens may not
      cause an immediate change in meal choices and nutrient intakes. The present study
      aimed at understanding the process by which the POP nutrition information
      achieved its effects on the meal choice and energy intake, and whether the
      information was more effective in changing the meal choice of subgroups of
      university canteen customers. METHODS: The POP nutrition-information intervention
      used a one-group pretest-posttest design. A sample of 224 customers of two
      university canteens completed the baseline and 6-months follow-up surveys. A
      multi-group structural equation modelling analysis was used to test mediation
      effects of individual difference variables (liking, understanding and use of the
      information, subjective knowledge and attitude) on the energy intake from canteen
      meals, moderated by the objective nutrition knowledge and motivation to change
      diet. RESULTS: Significant relations were identified between liking of the
      information and its use on one hand and a positive effect in attitude towards
      healthy canteen meals on the other hand. Motivation to change diet and sufficient
      objective nutrition knowledge were required to maintain a recommended energy
      intake from canteen meals or to lead to a decrease in energy intake. Participants
      with greater objective nutrition knowledge had a greater understanding of the POP
      nutrition information which also resulted in a more effective use of the
      information. CONCLUSIONS: The results suggest that nutrition-information
      interventions may be more effective when using nutrition information that is
      generally liked by the target population in combination with an educational
      intervention to increase objective nutrition knowledge.

PMID- 22967197
TI  - Monitoring costs in the ICU: a search for a pertinent methodology.
AB  - Attempts to determine costs in the intensive care unit (ICU) were not successful
      until now, as they failed to detect differences of costs between patients. The
      methodology and/or the instruments used might be at the origin of this failure.
      Based on the results of the European ICUs studies and on the descriptions of the
      activities of care in the ICU, we gathered and analysed the relevant literature
      concerning the monitoring of costs in the ICU. The aim was to formulate a
      methodology, from an economic perspective, in which future research may be
      framed. A bottom-up microcosting methodology will enable to distinguish costs
      between patients. The resulting information will at the same time support the
      decision-making of top management and be ready to include in the financial system
      of the hospital. Nursing staff explains about 30% of the total costs. This
      relation remains constant irrespective of the annual nurse/patient ratio. In
      contrast with other scoring instruments, the nursing activities score (NAS)
      covers all nursing activities. (1) NAS is to be chosen for quantifying nursing
      activities; (2) an instrument for measuring the physician's activities is not yet
      available; (3) because the nursing activities have a large impact on total costs,
      the standardisation of the processes of care (following the system approach) will
      contribute to manage costs, making also reproducible the issue of quality of
      care; (4) the quantification of the nursing activities may be the required
      (proxy) input for the automated bottom-up monitoring of costs in the ICU.

PMID- 22967199
TI  - Prepregnancy body mass index and congenital heart defects among offspring: a
      population-based study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the association between
      fetal development of congenital heart defects (CHD) and maternal prepregnancy
      body mass index (BMI, kg/m(2)) in the largest population-based case-control study
      to date. BACKGROUND: Mounting evidence implicates maternal obesity as a risk
      factor for birth defects. However, the association between maternal obesity and
      CHD in offspring has been less completely described. METHODS: We conducted a
      study of CHD using linked birth-hospital discharge records for Washington State
      between 1992-2007. All infants with CHD (n = 14,142) were identified based on
      ICD9-CM discharge diagnosis codes. 141,420 controls, frequency matched on year of
      delivery, were selected at random from among infants without CHD. Maternal BMI
      was calculated from maternal prepregnancy data. Odds ratios (OR) and 95%
      confidence intervals (CI) for the association of CHD relative to maternal BMI
      were calculated, adjusted for gestational diabetes. RESULTS: Infants with CHD
      were more likely to have an obese mother (OR 1.22, 95% CI 1.15-1.30). The
      strength of association increased with increasing BMI (BMI 30-34.9: OR 1.16, 95%
      CI 1.07-1.25; BMI 35-39.9: OR 1.25, 95% CI 1.13-1.39; BMI > = 40: OR 1.49, 95% CI
      1.32-1.69). The association was greatest for left and right ventricular outflow
      tract defects (OR 1.27, 95% CI 1.02-1.59 and OR 1.43, 95% CI 1.20-1.69,
      respectively). Hypoplastic left heart syndrome was markedly associated (OR 1.86,
      95% CI 1.13-3.05). There was no association with conotruncal defects (OR 1.04,
      95% CI: 0.82-1.33). CONCLUSIONS: We confirmed the association between CHD and
      maternal obesity and observed increasing risk with increasing obesity. Outflow
      tract defects appear uniquely associated. A greater risk of CHD among offspring
      is an important outcome of maternal obesity, and suggests a need for targeted
      medical management strategies.

PMID- 22967201
TI  - Short-term tracking of performance and health-related physical fitness in girls:
      the Healthy Growth in Cariri Study.
AB  - The main purpose of this study was to track the performance and health-related
      physical fitness of girls from Brazil's Cariri region. In the "Healthy Growth in
      Cariri Study", 294 girls from public and private schools were divided into four
      age cohorts--8, 10, 12, and 14 years--and followed for three consecutive years,
      with an assessment every 6 months. Shuttle run, hand grip, standing long jump,
      trunk lift, curl-up, 12-min run, and fatness were used to rate physical fitness
      performance and health-related components on each of six occasions. Tracking was
      done in a stepwise manner, using auto-correlation, by modelling the individual
      history of change in performance of each girl, and using Foulkes and Davies'
      gamma-coefficient. SPSS 18.0 and TIMEPATH were used for data analysis. Auto
      correlations evidenced low-to-moderate values in almost all components of
      performance and health-related physical fitness. Intra-individual tracking
      analysis showed large variation in all fitness components as a result of a wide
      spread in individual history of change in fitness performance. Population
      estimates of gamma were low in all tests. Our results show low-to-moderate
      tracking of physical fitness components of girls. A wide range of intra
      individual and inter-variability in fitness development was observed.

PMID- 22967200
TI  - Health numeracy in Japan: measures of basic numeracy account for framing bias in
      a highly numerate population.
AB  - BACKGROUND: Health numeracy is an important factor in how well people make
      decisions based on medical risk information. However, in many countries,
      including Japan, numeracy studies have been limited. METHODS: To fill this gap,
      we evaluated health numeracy levels in a sample of Japanese adults by translating
      two well-known scales that objectively measure basic understanding of math and
      probability: the 3-item numeracy scale developed by Schwartz and colleagues (the
      Schwartz scale) and its expanded version, the 11-item numeracy scale developed by
      Lipkus and colleagues (the Lipkus scale). RESULTS: Participants' performances (n
      = 300) on the scales were much higher than in original studies conducted in the
      United States (80% average item-wise correct response rate for Schwartz-J, and
      87% for Lipkus-J). This high performance resulted in a ceiling effect on the
      distributions of both scores, which made it difficult to apply parametric
      statistical analysis, and limited the interpretation of statistical results.
      Nevertheless, the data provided some evidence for the reliability and validity of
      these scales: The reliability of the Japanese versions (Schwartz-J and Lipkus-J)
      was comparable to the original in terms of their internal consistency (Cronbach's
      alpha = 0.53 for Schwartz-J and 0.72 for Lipkus-J). Convergent validity was
      suggested by positive correlations with an existing Japanese health literacy
      measure (the Test for Ability to Interpret Medical Information developed by
      Takahashi and colleagues) that contains some items relevant to numeracy.
      Furthermore, as shown in the previous studies, health numeracy was still
      associated with framing bias with individuals whose Lipkus-J performance was
      below the median being significantly influenced by how probability was framed
      when they rated surgical risks. A significant association was also found using
      Schwartz-J, which consisted of only three items. CONCLUSIONS: Despite relatively
      high levels of health numeracy according to these scales, numeracy measures are
      still important determinants underlying susceptibility to framing bias. This
      suggests that it is important in Japan to identify individuals with low numeracy
      skills so that risk information can be presented in a way that enables them to
      correctly understand it. Further investigation is required on effective numeracy
      measures for such an intervention in Japan.

PMID- 22967202
TI  - Internet-based self-help treatment for depression in multiple sclerosis: study
      protocol of a randomized controlled trial.
AB  - BACKGROUND: Depression in MS patients is frequent but often not treated
      adequately. An important underlying factor may be physical limitations that
      preclude face-to-face contact. Internet-based treatment showed to be effective
      for depressive symptoms in general and could thus be a promising tool for
      treatment in MS. METHODS/DESIGN: Here, we present a study protocol to investigate
      the effectiveness of a 5 week Internet-based self-help problem solving treatment
      (PST) for depressive symptoms in MS patients in a randomized controlled trial. We
      aim to include 166 MS patients with moderate to severe depressive symptoms who
      will be randomly assigned to an Internet-based intervention (with or without
      supportive text-messages) or waiting list control group. The primary outcome is
      the change in depressive symptoms defined by a change in the sum score on the
      Beck Depression Inventory (BDI-II). Secondary outcomes will include measures of
      anxiety, fatigue, cognitive functioning, physical and psychological impact of MS,
      quality of life, problem solving skills, social support, mastery, satisfaction
      and compliance rate. Assessments will take place at baseline (T0), within a week
      after the intervention (T1), at four months (T2) and at ten months follow-up (T3:
      only the intervention group). The control group will be measured at the same
      moments in time. Analysis will be based on the intention-to-treat principle.
      DISCUSSION: If shown to be effective, Internet-based PST will offer new
      possibilities to reach and treat MS patients with depressive symptoms and to
      improve the quality of care. TRIAL REGISTRATION: The Dutch Cochrane Center,
      NTR2772.

PMID- 22967203
TI  - Avian hepatitis E virus identified in Russian chicken flocks exhibits high
      genetic divergence based on the ORF2 capsid gene.
AB  - A total of 79 liver samples from clinically sick and asymptomatic chickens were
      tested for avian hepatitis E virus (aHEV). Samples were received from 19 farms,
      five of which tested positive with primers targeting the ORF2 capsid gene. The
      phylogenetic analysis of a 242-base-pair fragment demonstrated that the Russian
      aHEV isolates share between 78.2 and 96.2% over the fragment sequenced, whereas
      the nucleotide sequence identities between the Russian isolates and the other
      representatives from GeneBank varied from 76.3 to 96.2%. The homology between the
      studied hepatitis E viruses and swine hepatitis E virus varied between 46.9 to
      48.1%. The most divergent isolate aHEV16050 showed homology of 82.6% as compared
      with the strains in the dendrogram. The three positive hepatitis E virus samples
      (aHEV16279, aHEV16050 and aHEV18196) did not cluster with the European genotype 3
      as expected due to the close location of Russia to Europe, nor did they with the
      other two genotypes, separating to a distinct branch. The aHEV16211 grouped
      together with European and Chinese isolates, and the aHEV18198 with Canadian
      ones.

PMID- 22967204
TI  - Bacteremic nosocomial pneumonia caused by Acinetobacter baumannii and
      Acinetobacter nosocomialis: a single or two distinct clinical entities?
AB  - The phenotypically indistinguishable Acinetobacter baumannii and Acinetobacter
      nosocomialis have become leading pathogens causing nosocomial pneumonia in
      critically ill patients. A. baumannii and A. nosocomialis nosocomial pneumonias
      were grouped as a single clinical entity previously. This study aimed to
      determine whether they are the same or a different clinical entity. A total of
      121 patients with A. baumannii and 131 with A. nosocomialis bacteremic nosocomial
      pneumonia were included during an 8-year period. Despite the similar Charlson co
      morbidity scores at admission, patients with A. baumannii pneumonia were more
      likely to have abnormal haematological findings, lobar pneumonia, significantly
      higher Acute Physiology and Chronic Health Evaluation II scores and higher
      frequency of shock at the onset of bacteraemia than those with A. nosocomialis
      pneumoni. A. baumannii isolates were resistant to more classes of antimicrobials,
      except colistin, and therefore the patients with A. baumannii pneumonia were more
      likely to receive inappropriate antimicrobial therapy. The 14-day mortality was
      significantly higher in patients with A. baumannii pneumonia (34.7% vs. 15.3%, p
      0.001). A. baumannii was an independent risk factor for mortality (OR, 2.03; 95%
      CI, 1.05-3.90; p 0.035) in the overall cohort after adjustment for other risk
      factors for death, including inappropriate antimicrobial therapy. The results
      demonstrated the difference in clinical presentation, microbial characteristics
      and outcomes between A. baumannii and A. nosocomialis nosocomial pneumonia, and
      supported that they are two distinct clinical entities.

PMID- 22967205
TI  - Tuning the viscoelastic properties of bis(urea)-based supramolecular polymer
      solutions by adding cosolutes.
AB  - Polymers formed by the self-assembly of a bis(urea)-based polymer, 2,4-bis(2
      ethylhexylureido)toluene (EHUT), in organic solvents such as octane are promising
      systems with remarkable rheological properties. This is the first self-assembled
      polymer recently reported as a hydrodynamic drag reducer for hydrocarbons. The
      rheology of diluted and semidiluted EHUT solutions can be tuned by specific
      interactions between the chains, modulated by the nature of the solvent and the
      presence of additives. In this article, rheological, thermal and SANS
      measurements were performed in order to investigate the competition between EHUT
      self-assembly and its interaction with specific molecules (benzene, benzyl
      alcohol, and ethanol) that can interact with EHUT unimers via hydrogen bonds and
      pi-pi interactions. No substantial rheological, thermal, or structural effect is
      observed when benzene is added to the systems. However, ethanol and benzyl
      alcohol interact with EHUT unimers through hydrogen bonds, drastically decreasing
      the viscoelasticity of the solutions. In addition, benzyl alcohol can interact
      with EHUT polymers by pi-stacking interactions, playing an important role in
      tuning the rheological properties of the systems.

PMID- 22967206
TI  - Dynamic nuclear polarization NMR spectroscopy of microcrystalline solids.
AB  - Dynamic nuclear polarization (DNP) solid-state NMR has been applied to powdered
      microcrystalline solids to obtain sensitivity enhancements on the order of 100.
      Glucose, sulfathiazole, and paracetamol were impregnated with bis-nitroxide
      biradical (bis-cyclohexyl-TEMPO-bisketal, bCTbK) solutions of organic solvents.
      The organic solvents were carefully chosen to be nonsolvents for the compounds,
      so that DNP-enhanced solid-state NMR spectra of the unaltered solids could be
      acquired. A theoretical model is presented that illustrates that for externally
      doped organic solids characterized by long spin-lattice relaxation times
      (T(1)((1)H) > 200 s), (1)H-(1)H spin diffusion can relay enhanced polarization
      over micrometer length scales yielding substantial DNP enhancements (epsilon).
      epsilon on the order of 60 are obtained for microcrystalline glucose and
      sulfathiazole at 9.4 T and with temperatures of ca. 105 K. The large gain in
      sensitivity enables the rapid acquisition of (13)C-(13)C correlation spectra at
      natural isotopic abundance. It is anticipated that this will be a general method
      for enhancing the sensitivity of solid-state NMR experiments of organic solids.

PMID- 22967207
TI  - A novel gene, ardD, determines antirestriction activity of the non-conjugative
      transposon Tn5053 and is located antisense within the tniA gene.
AB  - The mercury-resistance transposon Tn5053 inhibits restriction activity of the
      type I restriction-modification endonuclease EcoKI in Escherichia coli K12 cells.
      This is the first report of antirestriction activity of a non-conjugative
      transposon. The gene (ardD) coding for the antirestriction protein has been
      cloned. The ardD gene is located within the tniA gene, coding for transposase, on
      the complementary strand. The direction of transcription is opposite to
      transcription of the tniA gene.

PMID- 22967208
TI  - Intravesical ropivacaine as a novel means of analgesia post-robot-assisted
      radical prostatectomy: a randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: This study evaluates the safety and efficacy of intravesical ropivacaine
      as part of a mulitimodal approach to the provision of analgesia after robot
      assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In this double
      blind, placebo-controlled trial, 40 patients who were scheduled to undergo RARP
      for treatment of localized prostate cancer by a single surgeon (SP) were
      randomized 1:1 to receive either alkalinized intravesical ropivacaine or placebo
      (0.9% sodium chloride) at the completion of the vesicourethral anastomosis. A
      standardized general anesthetic was administered in each case. The primary
      outcome was a reduction in postoperative pain as assessed by a visual analogue
      scale (VAS). The need for alternate analgesic agents was recorded. Adverse events
      related to the administration of intravesical ropivacaine were documented
      prospectively. RESULTS: No serious adverse events related to the administration
      of intravesical ropivacaine were identified. In the ropivacaine group, there was
      a significant reduction in the cumulative needed dose of ketoralac relative to
      placebo at 6 hours postoperatively. There was no statistically significant
      difference between the groups with regard to pain scores or narcotic use at any
      time point. CONCLUSIONS: Intravesical administration of ropivacaine may be used
      safely in the context of RARP and is associated with a significant, albeit modest
      reduction in the need for supplementary analgesic agents, but did not result in a
      decrease in postoperative pain scores.

PMID- 22967209
TI  - Methyl [13C]glucopyranosiduronic acids: effect of COOH ionization and exocyclic
      structure on NMR spin-couplings.
AB  - Methyl alpha- and beta-D-glucopyranuronides singly labeled with (13)C at C1-C6
      were prepared from the corresponding (13)C-labeled methyl D-glucopyranosides, and
      multiple NMR J-couplings (J(HH), J(CH), and J(CC)) were measured in their
      protonated and ionized forms in aqueous ((2)H(2)O) solution. Solvated density
      functional theory (DFT) calculations of J-couplings in structurally related model
      compounds were performed to determine how well the calculated J-couplings matched
      the experimental values in saccharides bearing an ionizable substituent.
      Intraring J(HH) values in both uronide anomers, including (3)J(H4,H5), are
      unaffected by solution pD, and COOH ionization exerts little effect on J(CH) and
      J(CC) except for (1)J(C1,H1), (1)J(C4,H4), (1)J(C5,H5), (1)J(C5,C6), and
      (2)J(C3,C5), where changes of up to 5 Hz were observed. Some of these changes are
      associated with changes in bond lengths upon ionization; in general, better
      agreement between theory and experiment was observed for couplings less sensitive
      to exocyclic C-O bond conformation. Titration of (1)H and (13)C chemical shifts,
      and some J-couplings, yielded a COOH pK(a) of 3.0 +/- 0.1 in both anomers. DFT
      calculations suggest that substituents proximal to the exocyclic COOH group
      (i.e., the C4-O4 bond) influence the activation barrier to C5-C6 bond rotation
      due to transient intramolecular H-bonding. A comparison of J-couplings in the
      glucopyranuronides to corresponding J-couplings in the glucopyranosides showed
      that more pervasive changes occur upon conversion from a COOH to a CH(2)OH
      substituent at C6 than from COOH ionization within the uronides. Twelve J
      couplings are affected, with the largest being (1)J(C5,C6) (~18 Hz larger in the
      uronides), followed by (2)J(C6,H5) (~2.5 Hz more negative in the uronides).

PMID- 22967210
TI  - Transversus abdominis block: clinical uses, side effects, and future
      perspectives.
AB  - Poorly controlled acute pain during the postoperative setting after abdominal
      surgery can be detrimental to the patient. Current pain management practices for
      the postoperative abdominal surgery patient rely heavily on opioids, which are
      associated with many unwanted side effects. Recently, interest surrounding
      regional anesthesia has been growing owing to its demonstrated efficacy and
      safety outcomes. More specifically, the transversus abdominis plane (TAP) block
      procedure has attracted attention owing to its ability to successfully block
      peripheral pain signaling in the abdomen, its ease of use, few complications, and
      its greater acceptability. A majority of the studies published has demonstrated
      the successful reduction in pain in many abdominal surgical procedures using
      local anesthetics during the TAP block. However, the short duration of the pain
      block causes the patient to still rely on other analgesics throughout the
      additional postoperative days. Preliminary studies using continuous infusion
      catheters placed in the TAP has been one of the ways to prolong the nerve block
      in the abdomen; however, technical and operational issues currently limit the
      widespread adoption of this method. In this review, current studies will be
      presented and summarized to update the field on the potential benefits of the TAP
      block procedure, in addition to providing insight into the future direction of
      the drugs that could be used for TAP block.

PMID- 22967211
TI  - Comment on "critical review of Pd-based catalytic treatment of priority
      contaminants in water".

PMID- 22967212
TI  - Phenolic compositions of 50 and 30 year sequences of Australian red wines: the
      impact of wine age.
AB  - The phenolic composition of red wine impacts upon the color and mouthfeel and
      thus quality of the wine. Both of these characteristics differ depending on the
      age of a wine, with the purple of young wines changing to brick red and the
      puckering or aggressive astringency softening in older wines. This study
      investigated the color parameters, tannin concentrations and tannin composition
      of a 50 year series of Cabernet Sauvignon wines from a commercial label as well
      as 30 year series of Cabernet Sauvignon and Shiraz wines from a separate
      commercial label to assess the impact of wine age on phenolic composition and
      concentration. The wine color density in wines of 40 to 50 years old was around 5
      AU compared with 16 AU of wine less than 12 months old, which correlated well
      with the concentration of non-bleachable pigments and pigmented polymers.
      Conversely, the anthocyanin concentrations in 10 year old wines were
      substantially lower than that of recently bottled wines (around 100 mg/L compared
      with 627 mg/L, respectively), adding further evidence that non-bleachable
      pigments including pigmented polymers play a much larger role in long-term wine
      color than anthocyanins. No age-related trend was observed for tannin
      concentration, indicating that the widely noted softer astringency of older red
      wines cannot necessarily be directly related to lower concentrations of soluble
      wine tannin and is potentially a consequence of changes in tannin structure. Wine
      tannins from older wines were generally larger than tannins from younger wines
      and showed structural changes consistent with oxidation. 

PMID- 22967213
TI  - Introduction to ultracold molecules: new frontiers in quantum and chemical
      physics.

PMID- 22967214
TI  - Excluded volume effect in the fluorescence energy transfer of single donor
      multiple acceptors in polymer.
AB  - Fluorescence resonance energy transfer (FRET) from a donor to multiple acceptors
      is an interesting subject. Numerous studies using theoretical models and
      simulations have focused on the excluded volume effect, which was not considered
      in Forster's first derivation. In this work, we first present the experimental
      results on the excluded volume effect by employing time-resolved FRET. Coumarin
      334 (C334) was used as the energy donor whereas hemin and cytochrome c (cyt c)
      were used as the energy acceptors. The fluorescence intensity decays were
      measured for C334 surrounded by a number of acceptors in poly(acrylic acid). We
      have observed that the excluded volume effect is markedly pronounced with cyt c
      compared with hemin when the acceptor concentration is high (>5 mM). The results,
      which may be explicitly described by the relative molecular sizes of two
      acceptors, showed that the excluded volume effect should be considered in the
      interpretation of FRET data, especially when bulk chromophores are used.

PMID- 22967215
TI  - 4D electron microscopy: principles and applications.
AB  - The transmission electron microscope (TEM) is a powerful tool enabling the
      visualization of atoms with length scales smaller than the Bohr radius at a
      factor of only 20 larger than the relativistic electron wavelength of 2.5 pm at
      200 keV. The ability to visualize matter at these scales in a TEM is largely due
      to the efforts made in correcting for the imperfections in the lens systems which
      introduce aberrations and ultimately limit the achievable spatial resolution. In
      addition to the progress made in increasing the spatial resolution, the TEM has
      become an all-in-one characterization tool. Indeed, most of the properties of a
      material can be directly mapped in the TEM, including the composition, structure,
      bonding, morphology, and defects. The scope of applications spans essentially all
      of the physical sciences and includes biology.  Until recently, however, high
      resolution visualization of structural changes occurring on sub-millisecond time
      scales was not possible. In order to reach the ultrashort temporal domain within
      which fundamental atomic motions take place, while simultaneously retaining high
      spatial resolution, an entirely new approach from that of millisecond-limited TEM
      cameras had to be conceived. As shown below, the approach is also different from
      that of nanosecond-limited TEM, whose resolution cannot offer the ultrafast
      regimes of dynamics. For this reason "ultrafast electron microscopy" is reserved
      for the field which is concerned with femtosecond to picosecond resolution
      capability of structural dynamics.  In conventional TEMs, electrons are produced
      by heating a source or by applying a strong extraction field. Both methods result
      in the stochastic emission of electrons, with no control over temporal spacing or
      relative arrival time at the specimen. The timing issue can be overcome by
      exploiting the photoelectric effect and using pulsed lasers to generate precisely
      timed electron packets of ultrashort duration. The spatial and temporal
      resolutions achievable with short intense pulses containing a large number of
      electrons, however, are limited to tens of nanometers and nanoseconds,
      respectively. This is because Coulomb repulsion is significant in such a pulse,
      and the electrons spread in space and time, thus limiting the beam coherence. It
      is therefore not possible to image the ultrafast elementary dynamics of complex
      transformations. The challenge was to retain the high spatial resolution of a
      conventional TEM while simultaneously enabling the temporal resolution required
      to visualize atomic-scale motions.  In this Account, we discuss the development
      of four-dimensional ultrafast electron microscopy (4D UEM) and summarize
      techniques and applications that illustrate the power of the approach. In UEM,
      images are obtained either stroboscopically with coherent single-electron packets
      or with a single electron bunch. Coulomb repulsion is absent under the single
      electron condition, thus permitting imaging, diffraction, and spectroscopy, all
      with high spatiotemporal resolution, the atomic scale (sub-nanometer and
      femtosecond). The time resolution is limited only by the laser pulse duration and
      energy carried by the electron packets; the CCD camera has no bearing on the
      temporal resolution. In the regime of single pulses of electrons, the temporal
      resolution of picoseconds can be attained when hundreds of electrons are in the
      bunch.  The applications given here are selected to highlight phenomena of
      different length and time scales, from atomic motions during structural dynamics
      to phase transitions and nanomechanical oscillations. We conclude with a brief
      discussion of emerging methods, which include scanning ultrafast electron
      microscopy (S-UEM), scanning transmission ultrafast electron microscopy (ST-UEM)
      with convergent beams, and time-resolved imaging of biological structures at
      ambient conditions with environmental cells.

PMID- 22967216
TI  - Comparative genomic analysis of Geobacter sulfurreducens KN400, a strain with
      enhanced capacity for extracellular electron transfer and electricity production.
AB  - BACKGROUND: A new strain of Geobacter sulfurreducens, strain KN400, produces more
      electrical current in microbial fuel cells and reduces insoluble Fe(III) oxides
      much faster than the wildtype strain, PCA. The genome of KN400 was compared to
      wildtype with the goal of discovering how the network for extracellular electron
      transfer has changed and how these two strains evolved. RESULTS: Both genomes
      were re-annotated, resulting in 14 fewer genes (net) in the PCA genome; 28 fewer
      (net) in the KN400 genome; and ca. 400 gene start and stop sites moved. 96% of
      genes in KN400 had clear orthologs with conserved synteny in PCA. Most of the
      remaining genes were in regions of genomic mobility and were strain-specific or
      conserved in other Geobacteraceae, indicating that the changes occurred post
      divergence. There were 27,270 single nucleotide polymorphisms (SNP) between the
      genomes. There was significant enrichment for SNP locations in non-coding or
      synonymous amino acid sites, indicating significant selective pressure since the
      divergence. 25% of orthologs had sequence differences, and this set was enriched
      in phosphorylation and ATP-dependent enzymes. Substantial sequence differences
      (at least 12 non-synonymous SNP/kb) were found in 3.6% of the orthologs, and this
      set was enriched in cytochromes and integral membrane proteins. Genes known to be
      involved in electron transport, those used in the metabolic cell model, and those
      that exhibit changes in expression during growth in microbial fuel cells were
      examined in detail. CONCLUSIONS: The improvement in external electron transfer in
      the KN400 strain does not appear to be due to novel gene acquisition, but rather
      to changes in the common metabolic network. The increase in electron transfer
      rate and yield in KN400 may be due to changes in carbon flux towards oxidation
      pathways and to changes in ATP metabolism, both of which indicate that the
      overall energy state of the cell may be different. The electrically conductive
      pili appear to be unchanged, but cytochrome folding, localization, and redox
      potentials may all be affected, which would alter the electrical connection
      between the cell and the substrate.

PMID- 22967217
TI  - High-density arrays of submicron spherical supported lipid bilayers.
AB  - Lipid bilayer membranes found in nature are heterogeneous mixtures of lipids and
      proteins. Model systems, such as supported lipid bilayers (SLBs), are often
      employed to simplify experimental systems while mimicking the properties of
      natural lipid bilayers. Here, we demonstrate a new method to form SLB arrays by
      first forming spherical supported lipid bilayers (SSLBs) on submicrometer
      diameter SiO(2) beads. The SSLBs are then arrayed into microwells using a simple
      physical assembly method that requires no chemical modification of the substrate
      nor modification of the lipid membrane with recognition moieties. The resulting
      arrays have submicrometer SSLBs with 3 MUm periodicity where >75% of the
      microwells are occupied by an individual SSLB. Because the arrays have high
      density, fluorescence from >1000 discrete SSLBs can be acquired with a single
      image capture. We show that 2-component random arrays can be formed, and we also
      use the arrays to determine the equilibrium dissociation constant for cholera
      toxin binding to ganglioside GM1. SSLB arrays are robust and are stable for at
      least one week in buffer.

PMID- 22967218
TI  - Identification and antibacterial characteristics of an endophytic fungus Fusarium
      oxysporum from Lilium lancifolium.
AB  - AIMS: The aim of this study is to isolate and identify an endophytic fungus with
      antibacterial activity from the Asian medicinal and culinary plant Lilium
      lancifolium and to study the characteristics of its major antibacterial
      fractions. METHODS AND RESULTS: After strict sample sterilization, an endophytic
      fungus BH-3 with great antibacterial activity against Leuconostoc mesenteroides
      was isolated from the bulbs of L. lancifolium and was identified as Fusarium
      oxysporum on the basis of internal transcribed spacer (ITS) rDNA sequence and
      morphological traits. After partial purification including superfiltration and
      gel filtration, the major antibacterial fractions were found to be the substances
      with the molecular mass ranging from 35 to 60kDa, mainly 55kDa. The partially
      purified antibacterial fractions were stable at thermal processes, with more than
      80% of activity left at 60 degrees C for 1h, and even 70.75% left at 121 degrees
      C for 15min. 90.33-98.97% of activity was observed in the pH range of 4.0-7.0.
      But the fractions were sensitive to different proteases. CONCLUSIONS: Endophytic
      strain F. oxysporum BH-3 isolated from the bulbs of L. lancifolium produced
      protein-like antibacterial metabolites. The antibacterial assay against Leuc.
      mesenteroides indicated that the fractions were stable at thermal processes and
      wide pH conditions, but sensitive to proteolyses. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides an increasing understanding of endophytic F. oxysporum
      in L. lancifolium and its metabolites, which have a great potential in food
      industry as antibacterial agents.

PMID- 22967219
TI  - One new pyrroline compound from Callistemon viminalis (Sol. Ex Gaertner) G.Don Ex
      Loudon.
AB  - One new compound: 3,4-dihydro-2-(hydroxymethyl)-4-methyl-2H-pyrrol-2-ol (5) was
      isolated from the fruits and bark of Callistemon viminalis along with the known
      compounds lupeol (1), octacosanol (2), beta-sitosterol (3), betulin (4),
      betulinic acid (6), ursolic acid (7), corosolic acid (8), beta-sitosterol-3-O
      beta-D-glucoside (9), methyl gallate (10), gallic acid (11), catechin (12),
      ellagic acid (13) and 3-O-acetylursolic acid (14) (compound 14 was isolated from
      the bark and not detected in the fruits). Structures of these compounds were
      elucidated on the basis of their spectroscopic data (NMR, MS, IR spectra and COSY
      and HR-MS for 5a). The antioxidant activity of the total extracts, petroleum
      ether, CH2Cl2 and EtOAc fractions together with the compounds 6, 7, 9, 10, 11, 12
      and 13 was comparable with that of the standard antioxidant, ascorbic acid. 

PMID- 22967220
TI  - Lifecourse factors and likelihood of rural practice and emigration: a survey of
      Ghanaian medical students.
AB  - INTRODUCTION: Health worker shortages and maldistribution have important
      implications for the capacity of health systems. Ghana has one of the highest
      physician emigration rates in the world, and over 75% of those who remain work in
      Ghana's two largest cities. The aim of this study was to investigate the
      contribution of experiential factors across Ghanaian medical students' lifespans
      on intent to practice in a rural area and intent to emigrate. METHODS: All fourth
      year medical students in Ghana were surveyed on demographics, rural and
      international experience, and future career plans. Key outcomes of interest were
      students' stated likelihood of practicing in a deprived rural area or emigrating
      after graduation. Lifecourse predictors of interest were parental socioeconomic
      status, gender, relationship status, rural and international living experience,
      and school of study. Bivariate and multivariate logistic regression were used to
      estimate associations between predictors and outcomes of interest. RESULTS: Of
      310 eligible students, 307 (99%) participated in the survey. Of these, 228 were
      Ghanaian and the focus of this analysis. It was found that 131 (57.5%) were
      willing to work in a deprived area in Ghana and 148 (64.9%) had considered
      emigrating after graduation. In the multivariate regression models, willingness
      to work in a deprived area was predicted by male gender (OR: 2.31, 95%CI: 1.23
      4.35), having lived in a rural area but never lived abroad (OR: 2.77, 95%CI: 1.08
      7.13), and low parental professional and educational status (OR: 2.33, 95%CI:
      1.23-4.43). Consideration of emigration was predicted by having lived abroad but
      never in a rural area (OR: 3.39, 95%CI: 1.15-9.97). A sub-set of 80 individuals
      (35%) reported that they were willing to work in a deprived area in Ghana but
      also considering emigration. These subjects were more likely to be male.
      CONCLUSIONS: Students with parents of a lower socioeconomic class, those with
      rural experience, and those without international experience are more likely to
      stay in Ghana and are also more likely to work in a deprived area after
      graduation. Selective admissions policies based on lifecourse factors combined
      with exposure to rural practice in medical school may have a role in increasing
      the number of rural physicians.

PMID- 22967221
TI  - Love the one you're with: proximity determines paternity success in the barnacle
      Tetraclita rubescens.
AB  - A species' mating system sets limits on the strength of sexual selection. Sexual
      selection is widespread in dioecious species, but is less well documented in
      hermaphrodites, and may be less important. We used four highly polymorphic
      microsatellite markers to assign paternity to broods of the hermaphroditic
      eastern Pacific volcano barnacle Tetraclita rubescens. These data were used to
      describe the species' mating system and to examine factors affecting male
      reproductive success. Tetraclita can sire broods over distances of 11.2 cm, but
      proximity to the sperm recipient had a highly significant effect on the
      probability of siring success. There was no effect of body size or the mass of
      male reproductive tissues on siring success. Broods showed relatively low
      frequencies of multiple paternity; even at high densities, 75% of broods had only
      one father. High frequencies of single-paternity broods imply either that this
      species does not compete via sperm displacement, or that sperm displacement is
      extremely effective, potentially explaining the lack of a positive relationship
      between male investment and paternity. In addition, there was low variance in
      siring success among individuals, suggesting a lack of strong sexual selection on
      male traits. Low variance among sires and the strong effect of proximity are
      probably driven by the unusual biology of a sessile copulating species.

PMID- 22967222
TI  - Key trends in interprofessional research: a macrosociological analysis from 1970
      to 2010.
AB  - The field of interprofessional research has grown both in size and in importance
      since the 1970s. In this paper, we use a macrosociological approach and a
      Bourdieusian theoretical framework to investigate this growth and the changing
      nature of the field's research. We investigate publication trends at the
      aggregate (field) level, using an original dataset of 100,488 interprofessional
      related articles published between 1970 and 2010 and recorded in the PubMed
      database. Articles were coded using a list of 638 codes that were then analyzed
      thematically and longitudinally. Our results are presented in two main sections.
      Initially, we consider the growth and reach of the interprofessional field.
      Second, we explore the five different trends ("terminological issues", "rising
      management rhetoric", "expansion of psychometrics", "shift from individualism to
      collectivism" and "emerging issues") that emerged out of our thematic analysis of
      publications over time. These findings are discussed in the light of Bourdieu's
      framework to provide an indication of what we argue is a growing legitimacy of
      the field of interprofessional research as a scholarly domain in its own right.

PMID- 22967223
TI  - Inferring an augmented Bayesian network to confront a complex quantitative
      microbial risk assessment model with durability studies: application to Bacillus
      cereus on a courgette puree production chain.
AB  - The Monte Carlo (MC) simulation approach is traditionally used in food safety
      risk assessment to study quantitative microbial risk assessment (QMRA) models.
      When experimental data are available, performing Bayesian inference is a good
      alternative approach that allows backward calculation in a stochastic QMRA model
      to update the experts' knowledge about the microbial dynamics of a given food
      borne pathogen. In this article, we propose a complex example where Bayesian
      inference is applied to a high-dimensional second-order QMRA model. The case
      study is a farm-to-fork QMRA model considering genetic diversity of Bacillus
      cereus in a cooked, pasteurized, and chilled courgette puree. Experimental data
      are Bacillus cereus concentrations measured in packages of courgette purees
      stored at different time-temperature profiles after pasteurization. To perform a
      Bayesian inference, we first built an augmented Bayesian network by linking a
      second-order QMRA model to the available contamination data. We then ran a Markov
      chain Monte Carlo (MCMC) algorithm to update all the unknown concentrations and
      unknown quantities of the augmented model. About 25% of the prior beliefs are
      strongly updated, leading to a reduction in uncertainty. Some updates
      interestingly question the QMRA model.

PMID- 22967224
TI  - Economic evaluation of a weight control program with e-mail and telephone
      counseling among overweight employees: a randomized controlled trial.
AB  - BACKGROUND: Distance lifestyle counseling for weight control is a promising
      public health intervention in the work setting. Information about the cost
      effectiveness of such interventions is lacking, but necessary to make informed
      implementation decisions. The purpose of this study was to perform an economic
      evaluation of a six-month program with lifestyle counseling aimed at weight
      reduction in an overweight working population with a two-year time horizon from a
      societal perspective. METHODS: A randomized controlled trial comparing a program
      with two modes of intervention delivery against self-help. 1386 Employees from
      seven companies participated (67% male, mean age 43 (SD 8.6) years, mean BMI 29.6
      (SD 3.5) kg/m2). All groups received self-directed lifestyle brochures. The two
      intervention groups additionally received a workbook-based program with phone
      counseling (phone; n=462) or a web-based program with e-mail counseling
      (internet; n=464). Body weight was measured at baseline and 24 months after
      baseline. Quality of life (EuroQol-5D) was assessed at baseline, 6, 12, 18 and 24
      months after baseline. Resource use was measured with six-monthly diaries and
      valued with Dutch standard costs. Missing data were multiply imputed. Uncertainty
      around differences in costs and incremental cost-effectiveness ratios was
      estimated by applying non-parametric bootstrapping techniques and graphically
      plotting the results in cost-effectiveness planes and cost-effectiveness
      acceptability curves. RESULTS: At two years the incremental cost-effectiveness
      ratio was ?1009/kg weight loss in the phone group and ?16/kg weight loss in the
      internet group. The cost-utility analysis resulted in ?245,243/quality adjusted
      life year (QALY) and ?1337/QALY, respectively. The results from a complete-case
      analysis were slightly more favorable. However, there was considerable
      uncertainty around all outcomes. CONCLUSIONS: Neither intervention mode was
      proven to be cost-effective compared to self-help.

PMID- 22967225
TI  - Degradation of chlorimuron-ethyl by Aspergillus niger isolated from agricultural
      soil.
AB  - Chlorimuron-ethyl, ethyl-2-[[[[(4-methoxy-6-chloro-pyrimidin-2
      yl)amino]carbonyl]amino] sulfonyl]benzoate, is used as a pre- and postemergence
      herbicide for the control of important broadleaved weeds in soybean and maize.
      Due to its phytotoxicity to rotation crops, concerns regarding chlorimuron
      contamination of soil and water have been raised. Although it is degraded in the
      agricultural environment primarily via pH- and temperature-dependent chemical
      hydrolysis, microbial transformation also has an important role. Fungi such as
      Fusarium and Alternaria are unable to survive in artificial media containing
      chlorimuron-ethyl at 25 mg L(-1) . However, Aspergillus niger survived in minimal
      broth containing chlorimuron at 2 mg mL(-1) . Aspergillus niger degraded the
      herbicide to harvest energy through two major routes of degradation. One route
      involves the cleavage of the sulfonylurea bridge, resulting in the formation of
      two major metabolites, namely ethyl-2-aminosulfonylbenzoate (I) and 4-methoxy-6
      chloro-2-amino-pyrimidine (II). The other route is the cleavage of sulfonylamide
      linkage, which generates the metabolite N-(4-methoxy-6-chloropyrimidin-2-yl) urea
      (III). Two other metabolites, saccharin (IV) and N-methyl saccharin (V), formed
      from metabolite II, were also identified. A metabolic pathway for the degradation
      of chlorimuron-ethyl by A. niger has been proposed.

PMID- 22967227
TI  - Social cognition and metacognition in schizophrenia: evidence of their
      independence and linkage with outcomes.
AB  - OBJECTIVE: Research suggests that many with schizophrenia experience deficits in
      the ability to make discrete judgments about the thoughts and feelings of others
      as well as to form larger integrated representations of themselves and others.
      Little is known about whether these difficulties may be distinguished from one
      another and whether they are linked with different outcomes. METHOD: We
      administered three assessments of social cognition which tapped the ability to
      identify emotions and intentions and two metacognitive tasks which called for the
      formation of more integrated and flexible representations of the self and others.
      We additionally assessed symptoms, social functioning and neurocognition.
      Participants were 95 individuals with a schizophrenia spectrum disorder. RESULTS:
      A principle components analysis followed by a varimax rotation revealed two
      factors which accounted for 62% of the variance. The first factor was comprised
      of the three social cognition tests and the second of two tasks that tapped the
      ability to create representations of oneself and others which integrate more
      discreet information. The first factor was uniquely correlated with negative
      symptoms, and the second was uniquely correlated with social function.
      CONCLUSION: Results suggest that deficits in social cognition and metacognition
      represent different forms of dysfunction in schizophrenia.

PMID- 22967228
TI  - Successful percutaneous recanalization of thrombosed major aortopulmonary
      collateral artery in palliated tetralogy of fallot with pulmonary atresia.
AB  - We report the case of a 25-year-old male with palliated tetralogy of Fallot and
      pulmonary atresia presenting with thrombotic occlusion of a major aortopulmonary
      collateral artery to the right lung. Percutaneous intervention was successful in
      recanalizing this vessel, resulting in symptomatic improvement. 

PMID- 22967226
TI  - Aqueous-based initiator attachment and ATRP grafting of polymer brushes from
      poly(methyl methacrylate) substrates.
AB  - Many polymers, such as PMMA, are very susceptible to swelling or dissolution by
      organic solvents. Growing covalently attached polymer brushes from these surfaces
      by atom-transfer radical polymerization (ATRP) is challenging because of the
      typical requirement of organic solvent for initiator immobilization. We report an
      unprecedented, aqueous-based route to graft poly(N-isopropylacrylamide), PNIPAAm,
      from poly(methyl methacrylate), PMMA, surfaces by ATRP, wherein the underlying
      PMMA is unaffected. Successful attachment of the ATRP initiator, N
      hydroxysuccinimidyl-2-bromo-2-methylpropionate, on amine-bearing PMMA surfaces
      was confirmed by XPS. From this surface-immobilized initiator, thermoresponsive
      PNIPAAm brushes were grown by aqueous ATRP to yield optically transparent PNIPAAm
      grafted PMMA surfaces. This procedure is valuable, as it can be applied for the
      aqueous-based covalent attachment of ATRP initiator on any amine-functionalized
      surface, with subsequent polymerization of a variety of monomers.

PMID- 22967229
TI  - The practicality of nanoceria-PAN-based (68)Ge/(68)Ga generator toward
      preparation of (68)Ga-labeled cyclic RGD dimer as a potential PET radiotracer for
      tumor imaging.
AB  - Cyclic RGD (Arg-Gly-Asp) peptides radiolabeled with (68)Ga have great potential
      for the early tumor detection and noninvasive monitoring of tumor metastasis and
      therapeutic response. Herein, the preparation of (68)Ga-labeled DOTA
      E[c(RGDfK)](2) (DOTA=1,4,7,10-tetraazacylododecane-1,4,7,10-tetracetic acid;
      E=Glutamic acid; R=Arginine; G=Glycine; D=Aspartic acid; f=phenyl alanine;
      K=lysine) using (68)Ga directly eluted from a nanoceria-polyacrylonitrile (CeO(2)
      PAN)-based (68)Ge/(68)Ga generator developed in-house was reported. The (68)Ga
      complex of DOTA-E[c(RGDfK)](2) was synthesized with >98% radiochemical purity by
      incubating 20 MUg of the conjugate with (68)GaCl(3) (74-111 MBq) in acetate
      buffer (pH 3.5-4.0) at 90 degrees C for 10 minutes. The complex exhibited
      excellent in vitro stability in 0.1 M EDTA solution at room temperature upto 1
      hour studied (radiochemical purity: 98.0%). The biological efficacy of the
      radiolabeled conjugate was studied in C57/BL6 mice bearing melanoma tumors. The
      results of the biodistribution studies revealed significant tumor uptake (4.14+/
      0.54%ID/g) within 10 minutes postinjection (p.i.), which increased further to
      4.61+/-0.31%ID/g at 30 minutes p.i. The tumor-to-blood ratio was found to
      increase from 1.75+/-0.42 at 10 minutes p.i. to 2.25+/-0.20 at 60 minutes p.i.,
      whereas the tumor-to-liver and tumor-to-muscle ratio between the same time points
      increased from 2.71+/-0.76 to 3.31+/-0.84 and 5.37+/-1.08 to 8.97+/-1.32,
      respectively. The study successfully demonstrated the preparation of (68)Ga-DOTA
      E[c(RGDfK)](2) as a potential positron-emission tomography radiotracer for
      possible use in tumor imaging by using (68)Ga eluted from a reliable, easy-to
      handle (68)Ge/(68)Ga generator developed in-house, without any postelution
      purification of (68)Ga.

PMID- 22967230
TI  - Using mass-media communications to increase population usage of Australia's Get
      Healthy Information and Coaching Service(r).
AB  - BACKGROUND: Global obesity prevalence is increasing and population health
      programs are required to support changes to modifiable lifestyle risk factors.
      Such interventions benefit from mass-communications to promote their use. The Get
      Healthy Information and Coaching Service (r) (GHS) utilised mass-reach media
      advertising to recruit participants to an Australian state-wide program. METHODS:
      A stand alone population survey collected awareness, knowledge and behavioural
      variables before the first advertising phase, (n = 1,544; August -September
      2010), during (n = 1,500; February - March 2011) and after the advertising period
      (n = 1,500; June-July 2011). GHS usage data (n = 6,375) was collated during July
      2010 - June 2011. RESULTS: The results showed that television-lead mass-media
      significantly increased unprompted awareness (0% to 31.8%, p < 0.001); prompted
      awareness (2.5% to 23.7%, p < 0.001); and understanding (10.2% to 32.2%, p <
      0.001). Mass-media (television, print and mail out information) was more often
      cited as the source of referral by males, those aged 18 - 49 years, employed, and
      from the lowest socio-economic groups. During the weeks when mass-media
      advertising was present, 4 and 2.5 times more information and coaching
      participants respectively registered than when there was no advertising present.
      Participants who cited television and print were less likely to enrol in GHS
      coaching, but this was not the case for mail out information and secondary
      referral sources. CONCLUSIONS: GHS mass-communications campaigns are effective at
      increasing awareness and usage of the GHS, especially among hard-to-reach
      population groups. Television advertising provides universal reach, but should be
      supplemented by health professional referrals and targeted mail-out information
      to recruit participants to the intensive GHS coaching program.

PMID- 22967232
TI  - Durability of running shoes with ethylene vinyl acetate or polyurethane midsoles.
AB  - Ethylene vinyl acetate and polyurethane are widely used materials for shoe
      midsoles. The present study investigated the durability of running shoes made
      from ethylene vinyl acetate and one type of polyurethane (polyurethane-1), which
      have similar hardness and density, and another type of polyurethane (polyurethane
      2), which has high hardness/density. All shoes differed from one another only in
      terms of the midsole material used. Eight male runners participated in the
      present study and used the shoes to run 500 km (10 * 50 km). The cushioning and
      energy return characteristics of each shoe were measured using an impact tester
      before and after each 50-km run. The results showed that as the running distance
      increased, the peak force of midsole materials changed with different patterns.
      Ethylene vinyl acetate and polyurethane-1 showed greater cushioning than
      polyurethane-2 over 500 km (ethylene vinyl acetate, 918.2-968.0 N; polyurethane
      1, 909.6-972.9 N; polyurethane-2, 983.0-1105.6 N). Polyurethane-1 showed greater
      cushioning from 200 km to 300 km compared with 0 km (0 km, 972.9 +/- 66.3 N; 200
      km, 909.6 +/- 61.2 N; 250 km, 921.9 +/- 51.2 N; 300 km, 924.6 +/- 51.9 N). The
      cushioning of ethylene vinyl acetate shoes was diminished after 500 km compared
      with that at 0 km (968.0 +/- 25.9 N vs. 921.1 +/- 20.1 N). Ethylene vinyl acetate
      resulted in greater energy returns than polyurethane. Both foam category and
      hardness/density affected the critical biomechanical properties of running shoes.

PMID- 22967231
TI  - Users' perspectives of key factors to implementing electronic health records in
      Canada: a Delphi study.
AB  - BACKGROUND: Interoperable electronic health record (EHR) solutions are currently
      being implemented in Canada, as in many other countries. Understanding EHR users'
      perspectives is key to the success of EHR implementation projects. This Delphi
      study aimed to assess in the Canadian context the applicability, the importance,
      and the priority of pre-identified factors from a previous mixed-methods
      systematic review of international literature. METHODS: A three-round Delphi
      study was held with representatives of 4 Canadian EHR user groups defined as
      partners of the implementation process who use or are expected to use EHR in
      their everyday activity. These groups are: non-physician healthcare
      professionals, health information professionals, managers, and physicians. Four
      bilingual online questionnaire versions were developed from factors identified by
      the systematic review. Participants were asked to rate the applicability and the
      importance of each factor. The main outcome measures were consensus and priority.
      Consensus was defined a priori as strong (>= 75%) or moderate (>= 60-74%)
      according to user groups' level of agreement on applicability and importance,
      partial (>= 60%) when participants agreed only on applicability or importance, or
      as no consensus (< 60%). Priority for decision-making was defined as factors with
      strong consensus with scores of 4 or 5 on a five-point Likert scale for
      applicability and importance. RESULTS: Three Delphi rounds were completed by 64
      participants. Levels of consensus of 100%, 64%, 64%, and 44% were attained on
      factors submitted to non-physician healthcare professionals, health information
      professionals, managers, and physicians, respectively. While agreement between
      and within user groups varied, key factors were prioritized if they were
      classified as strong (>= 75% from questionnaire answers of user groups), for
      decision-making concerning EHR implementation. The 10 factors that were
      prioritized are perceived usefulness, productivity, motivation, participation of
      end-users in the implementation strategy, patient and health professional
      interaction, lack of time and workload, resources availability, management,
      outcome expectancy, and interoperability. CONCLUSIONS: Amongst all factors
      influencing EHR implementation identified in a previous systematic review, ten
      were prioritized through this Delphi study. The varying levels of agreement
      between and within user groups could mean that users' perspectives of each factor
      are complex and that each user group has unique professional priorities and roles
      in the EHR implementation process. As more EHR implementations in Canada are
      completed it will be possible to corroborate this preliminary result with a
      larger population of EHR users.

PMID- 22967233
TI  - Conductance switching in the photoswitchable protein Dronpa.
AB  - Dronpa, a photoswitchable GFP-like protein, was self-assembled onto gold
      substrates, and its conductance was measured using scanning tunneling microscopy
      (STM) and scanning tunneling spectroscopy (STS).

PMID- 22967235
TI  - Renal volumetric analysis: a new paradigm in renal mass treatment assessment.
AB  - Abstract Background and Purpose: Multiple renal volumetric assessment studies
      have correlated parenchymal volume with the glomerular filtration rate. The
      objective of this study was to compare renal volumes before and after treatment
      of renal masses with either partial nephrectomy or radiofrequency ablation (RFA).
      PATIENTS AND METHODS: We reviewed our prospectively collected database of
      patients with renal masses who were treated between November 2001 and January
      2011 with robot-assisted laparoscopic partial nephrectomy (RALPN), laparoscopic
      RFA (LRFA), or CT-guided percutaneous RFA (CTRFA). Digital Imaging and
      Communications in Medicine CT imaging data were analyzed in an open-source
      viewer. Volumetric calculations were used to measure the normal, enhancing
      bilateral renal parenchyma and tumor volumes. Normal parenchymal volume loss was
      compared among treatments. RESULTS: There were 96 patients (68 men) with an
      average age of 68.0 (36-84) years who met our inclusion criteria. The average
      tumor diameter, tumor volume, and nephrometry score (NS) was 3.5 cm, 32.0 cm(3),
      and 7.1 in RALPN (n=26), 2.6 cm, 9.8 cm(3), and 7.1 in CTRFA (n=47), and 2.9 cm,
      14.3 cm(3), and 7.2 in LRFA (n=23) groups. The percent change in the operated
      kidney volume was similar in RALPN (-12%+/-15), CTRFA (-13%+/-16), and LRFA (
      17%+/-18) groups. NS was the only variable in a multivariate linear regression
      model that correlated with the amount of volume lost in the ipsilateral kidney.
      CONCLUSIONS: Our retrospective volumetric analysis of renal parenchyma before and
      after partial nephrectomy or RFA of renal masses revealed that all treatments
      produce similar volume of collateral damage.

PMID- 22967236
TI  - Borrelidin, a potent antifungal agent: insight into the antifungal mechanism
      against Phytophthora sojae.
AB  - Borrelidin has high and specific antifungal activity against  Phytophthora sojae
      . To explore the antifungal mechanism of borrelidin against  P. sojae , the
      relationship between the antifungal activity of borrelidin and the concentration
      of threonine was evaluated. The results demonstrated that the growth-inhibitory
      effect of borrelidin on the growth of  P. sojae  was antagonized by threonine in
      a dose-dependent manner, suggesting that threonyl-tRNA synthetase (ThrRS) may be
      the potential target of borrelidin. Subsequently, the inhibition of the enzymatic
      activity of ThrRS by borrelidin in vitro was confirmed. Furthermore, the detailed
      interaction between ThrRS and borrelidin was investigated using fluorescence
      spectroscopy and circular dichroism (CD), implying a tight binding of borrelidin
      to ThrRS. Taken together, these results suggest that the antifungal activity of
      borrelidin against  P. sojae  was mediated by inhibition of ThrRS via the
      formation of the ThrRS-borrelidin complex.

PMID- 22967234
TI  - Optimal timing for initiation of highly active antiretroviral therapy in
      treatment-naive human immunodeficiency virus-1-infected individuals presenting
      with AIDS-defining diseases: the experience of the PISCIS Cohort.
AB  - In this prospective, multicentre cohort study, we analysed specific prognostic
      factors and the impact of timing of highly active antiretroviral therapy (HAART)
      on disease progression and death among 625 human immunodeficiency virus (HIV)-1
      infected, treatment-naive patients diagnosed with an AIDS-defining disease. HAART
      was classified as early (<30 days) or late (30-270 days). Deferring HAART was
      significantly associated with faster progression to a new AIDS-defining
      event/death overall (p 0.009) and in patients with Pneumocystis jiroveci
      pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated
      with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio
      1.83; 95% CI 1.25-2.68). Other independent risk factors for poorer outcome were
      baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4(+) count
      (<50 cells/MUL).

PMID- 22967237
TI  - Molecular dynamic simulations of the binary complex of human tissue factor (TF(1
      242) ) and factor VIIa (TF(1-242) /FVIIa) on a 4:1 POPC/POPS lipid bilayer.

PMID- 22967238
TI  - Fate and transformation of an estrogen conjugate and its metabolites in
      agricultural soils.
AB  - In the environment, conjugated estrogens are nontoxic but may hydrolyze to their
      potent unconjugated, 'free' forms. Compared to free estrogens, conjugated
      estrogens would be more mobile in the environment because of their higher water
      solubility. To identify the fate of a conjugated estrogen in natural agricultural
      soils, batch experiments were conducted with a (14)C labeled prototype conjugate,
      17beta-estradiol-3-glucuronide (E2-3G). Initially, aqueous dissipation was
      dominated by biological hydrolysis of E2-3G and its oxidized metabolite, estrone
      glucuronide (E1-3G), both of which were transformed into the free estrogens,
      17beta-estradiol (E2) and estrone (E1), respectively. Following hydrolysis,
      hydrophobic sorption interactions of E2 and E1 dominated. Depending on soil
      organic matter contents, dissolved E2-3G persisted from 1-14 d, which was much
      longer than what others reported for free estrogens (generally <24 h).
      Biodegradation rate constants of E2-3G were smaller in the subsoil (0.01-0.02 h(
      1)) compared to topsoil (0.2-0.4 h(-1)). Field observations supported our
      laboratory findings where significant concentrations (425 ng L(-1)) of intact E2
      3G were detected in groundwater (6.5-8.1 m deep) near a swine (Sus scrofa
      domesticus) farm. This study provides evidence that conjugate estrogens may be a
      significant source of free estrogens to surface water and groundwater.

PMID- 22967240
TI  - From chiral ortho-benzoquinone monoketals to nonracemic indolinocodeines through
      Diels-Alder and Cope reactions.
AB  - The S-dienol (-)-4 containing 10 carbons and one oxygen of the final product was
      prepared in 98.6% ee and 39% yield from cyclohexan-1,3-dione. It was attached to
      the aromatic ring as a monoether of catechol S-(-)-6 and subsequently subjected
      to oxidative ketalization in methanol. The allylated phenanthrofuran obtained was
      selectively oxidized at the terminal double bond. The fifth ring was completed by
      a "one-pot" amidation-cyclization process promoted by palladium acetate. The
      final homochiral indolinocodeine (-)-31 was obtained in 16 steps and 3.6% overall
      yield from cyclohexan-1,3-dione.

PMID- 22967239
TI  - Measuring the grafting density of nanoparticles in solution by analytical
      ultracentrifugation and total organic carbon analysis.
AB  - Many of the solution phase properties of nanoparticles, such as their colloidal
      stability and hydrodynamic diameter, are governed by the number of stabilizing
      groups bound to the particle surface (i.e., grafting density). Here, we show how
      two techniques, analytical ultracentrifugation (AUC) and total organic carbon
      analysis (TOC), can be applied separately to the measurement of this parameter.
      AUC directly measures the density of nanoparticle-polymer conjugates while TOC
      provides the total carbon content of its aqueous dispersions. When these
      techniques are applied to model gold nanoparticles capped with thiolated
      poly(ethylene glycol), the measured grafting densities across a range of polymer
      chain lengths, polymer concentrations, and nanoparticle diameters agree to within
      20%. Moreover, the measured grafting densities correlate well with the polymer
      content determined by thermogravimetric analysis of solid conjugate samples.
      Using these tools, we examine the particle core diameter, polymer chain length,
      and polymer solution concentration dependence of nanoparticle grafting densities
      in a gold nanoparticle-poly(ethylene glycol) conjugate system.

PMID- 22967241
TI  - Self-diffusion and viscosity in electrolyte solutions.
AB  - The effect of salt on the dynamics of water molecules follows the Hofmeister
      series. For some "structure-making" salts, the self-diffusion coefficient of the
      water molecules, D, decreases with increasing salt concentration. For other
      "structure-breaking" salts, D increases with increasing salt concentration. In
      this work, the concentration and temperature dependence of the self-diffusion of
      water in electrolyte solutions is studied using molecular dynamics simulations
      and pulsed-field-gradient NMR experiments; temperature-dependent viscosities are
      also independently measured. Simulations of rigid, nonpolarizable models at room
      temperature show that none of the many models tested can reproduce the
      experimentally observed trend for the concentration dependence of D; that is, the
      models predict that D decreases with increasing salt concentration for both
      structure-breaking and structure-making salts. Predictions of polarizable models
      are not in agreement with experiment either. These results suggest that many
      popular water models do not accurately describe the dynamic nature of the
      hydrogen bond network of water at room temperature. The simulations are in
      qualitative agreement, however, with experimental results for the temperature
      dependence of water dynamics; simulations and experiment show an Arrhenius
      dependence of D with temperature, T, with added salt, that is, ln D ~ 1/T, over a
      range of temperatures above the freezing point of water.

PMID- 22967242
TI  - Microfluidic multifunctional probe array dielectrophoretic force spectroscopy
      with wide loading rates.
AB  - The simultaneous investigation of a large number of events with different types
      of intermolecular interactions, from nonequilibrium high-force pulling assays to
      quasi-equilibrium unbinding events in the same environment, can be very important
      for fully understanding intermolecular bond-rupture mechanisms. Here, we describe
      a novel dielectrophoretic force spectroscopy technique that utilizes microsized
      beads as multifunctional probes for parallel measurement of intermolecular forces
      with an extremely wide range of force rate (10(-4) to 10(4) pN/s) inside a
      microfluidic device. In our experiments, various forces, which broadly form the
      basis of all molecular interactions, were measured across a range of force
      loading rates by multifunctional probes of various diameters with a throughput of
      over 600 events per mm(2), simultaneously and in the same environment.
      Furthermore, the individual bond-rupture forces, the parameters for the
      characterization of entire energy landscapes, and the effective stiffness of the
      force spectroscopy were determined on the basis of the measured results. This
      method of determining intermolecular forces could be very useful for the precise
      and simultaneous examination of various molecular interactions, as it can be
      easily and cost-effectively implemented within a microfluidic device for a range
      of applications including immunoassays, molecular mechanics, chemical and
      biological screening, and mechanobiology.

PMID- 22967243
TI  - Stability of human enteric viruses in seawater samples from mollusc depuration
      tanks coupled with ultraviolet irradiation.
AB  - AIMS: To evaluate the stability in seawater of human adenovirus (HAdV2), murine
      norovirus (MNV-1) and hepatitis A virus (HAV) in a shellfish depuration system
      with and without ultraviolet (UV) treatment. METHODS AND RESULTS: Seawater was
      seeded with viruses and disinfected using a 36 W lamp. Samples were collected at
      24, 48, 72, 96 and 120 h; viruses were concentrated and the viral decay was
      evaluated using molecular and cell culture methods. Based on the molecular
      results, at 120 h of disinfection, there was a reduction of more than 3 log(10)
      for HAdV2 and HAV; MNV-1, a 4.5 log(10) reduction was observed at 72 h.
      Infectious MNV-1 was not detected after 72 h of treatment; while HAdV2 remained
      infectious. Seawater not treated demonstrated a progressive viral reduction for
      the three viruses tested. CONCLUSIONS: The UV reduced the number of viral
      particles, and the results indicate there is natural and gradual decrease of
      viral load and viability in seawater. SIGNIFICANCE AND IMPACT OF THE STUDY: UV
      irradiation is the method of choice for shellfish depuration in many countries;
      this work showed useful information about the viral stability in seawater and
      application of UV to water disinfection to be used in shellfish depuration tanks.

PMID- 22967244
TI  - Characterization of functional mannose receptor in a continuous hybridoma cell
      line.
AB  - BACKGROUND: The mannose receptor is the best described member of the type I
      transmembrane C-type lectins; however much remains unanswered about the biology
      of the receptor. One difficulty has been the inability to consistently express
      high levels of a functional full length mannose receptor cDNA in mammalian cells.
      Another difficulty has been the lack of a human macrophage cell line expressing a
      fully functional receptor. Commonly used human macrophage cell lines such as
      U937, THP-1, Mono-Mac and HL60 do not express the mannose receptor. We have
      developed a macrophage hybridoma cell line (43MR cells) created by fusion of U937
      cells with primary human monocyte-derived macrophages, resulting in a non
      adherent cell line expressing several properties of primary macrophages. The
      purpose of this study was to identify and select mannose receptor-expressing
      cells using fluorescence-activated cell sorting and to characterize the
      expression and function of the receptor. RESULTS: In the current study we show
      that the mannose receptor found on this novel cell has endocytic characteristics
      consistent with and similar to the mannose receptor found on the surface of
      monocyte-derived human macrophages and rat bone marrow-derived macrophages. In
      addition, we demonstrate that these cells engage and internalize pathogen
      particles such as S. aureus and C. albicans. We further establish the
      transfectability of these cells via the introduction of a plasmid expressing
      influenza A hemagglutinin. CONCLUSIONS: The 43MR cell line represents the first
      naturally expressed MR-positive cell line derived from a human macrophage
      background. This cell line provides an important cell model for other researchers
      for the study of human MR biology and host-pathogen interactions.

PMID- 22967246
TI  - Extracellular volume fraction mapping in the myocardium, part 2: initial clinical
      experience.
AB  - BACKGROUND: Diffuse myocardial fibrosis, and to a lesser extent global myocardial
      edema, are important processes in heart disease which are difficult to assess or
      quantify with cardiovascular magnetic resonance (CMR) using conventional late
      gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial
      extracellular volume fraction (ECV) circumvents factors that confound T1-weighted
      images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV
      would be clinically useful for detecting both focal and diffuse myocardial
      abnormalities in a variety of common and uncommon heart diseases. METHODS: A
      total of 156 subjects were imaged including 62 with normal findings, 33 patients
      with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy
      (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute
      myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak
      syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1
      maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally
      elevated ECV was defined as >2SD from the mean ECV in individuals with normal
      findings. In HCM the size of regions of LGE was quantified as the region >2 SD
      from remote. RESULTS: Mean ECV of 62 normal individuals was 25.4 +/- 2.5% (m +/-
      SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial
      infarctions (without MVO) (N=33) measured 68.5 +/- 8.6% (p<0.001 vs normal). In
      HCM, the extent of abnormally elevated ECV correlated to the extent of LGE
      (r=0.72, p<0.001) but had a systematically greater extent by ECV (mean difference
      19 +/- 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients
      with non-ischemic DCM (38.1 +/- 1.9% (p<0.001 vs normal) and LGE in the same
      slice appeared "normal" in 2 of these 4 patients. Mean ECV values in other
      disease entities ranged 32-60% for cardiac amyloidosis (N=4), 40-41% for systemic
      capillary leak syndrome (N=2), and 39-56% within abnormal regions affected by
      myocarditis (N=7). CONCLUSIONS: ECV mapping appears promising to complement LGE
      imaging in cases of more homogenously diffuse disease. The ability to display ECV
      maps in units that are physiologically intuitive and may be interpreted on an
      absolute scale offers the potential for detection of diffuse disease and
      measurement of the extent and severity of abnormal regions.

PMID- 22967247
TI  - Someone to talk to: young mothers' experiences of participating in a young
      parents support programme.
AB  - AIMS: To identify young parents' perceptions and experiences of a parenting
      support programme, run by a non-government organisation, which provided both
      community group-based, and one-on-one home visiting, support. STUDY DESIGN: A
      qualitative descriptive study was conducted in one of the most socio-economically
      disadvantaged areas of Sydney, NSW; this is also an area with one of the highest
      percentage of births among young parents. Young parents were eligible to
      participate whether they attended one of the parenting groups and/or received
      professional home visiting through the young parents programme. Eighteen young
      women were interviewed, and a further ten participated in a focus group. Thematic
      analysis of the focus groups and interviews was undertaken. FINDINGS: Four themes
      were identified in the analysis: 'someone I know and trust', 'we just talk about
      anything and everything', 'doing the personal' and 'getting out and relaxing'.
      These themes were linked through the common thread of relationships; the
      relationships between themselves and other young mothers, and with the workers on
      the programme. The characteristics of the person with whom they had a
      relationship, the type of relationship, the content of their interactions and the
      benefits of these relationships were all important. CONCLUSIONS: This study is
      limited by the small sample size and the 'low risk' status of the young parents
      who engaged in the programme. This study demonstrated not only the importance for
      young parents of all forms of interaction, whether it is one-on-one, in a group
      or social networking; but most importantly, the benefits of having someone to
      talk to.

PMID- 22967248
TI  - Periodontal health and serum, saliva matrix metalloproteinases in patients with
      mild chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: The present case-control study aimed to evaluate
      comparatively the salivary and serum levels of matrix metalloproteinases (MMP)-8
      and- 13 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients
      with mild chronic obstructive pulmonary disease (COPD) and non-COPD controls.
      MATERIAL AND METHODS: Clinical periodontal measurements were recorded before any
      periodontal intervention in 36 patients with mild COPD and 20 non-COPD controls
      admitted to Ege University Department of Chest Diseases COPD outpatient clinic
      (Izmir, Turkey). Salivary and serum levels of MMP-8, MMP-13, and TIMP-1 were
      determined by immunofluorometric assay (IFMA) and enzyme-linked immunosorbent
      assay (ELISA). Data were analyzed with non-parametric statistical tests. RESULTS:
      Patients with COPD were significantly older than the control group (p < 0.05).
      The COPD group showed significantly higher serum levels of MMP-8 IFMA, MMP-8/TIMP
      1 IFMA than the control group (p < 0.005). By ELISA, serum MMP-8, MMP-8/TIMP-1,
      TIMP-1, and MMP-13 levels were similar in both groups (p > 0.05). Salivary MMP-8,
      MMP-13, and TIMP-1 levels were similar in both groups (p > 0.05). CONCLUSIONS:
      The present findings suggest that immunodetection of MMP-8 is dependent on the
      selected techniques and even with mild COPD some systemic inflammatory markers
      such as MMP-8 tend to increase. However, the present clinical periodontal and
      biochemical findings do not provide support for the previously proposed
      interaction between COPD and periodontal diseases.

PMID- 22967249
TI  - Applying sodium profile with or without ultrafiltration profile failed to show
      beneficial effects on the incidence of intradialytic hypotension in susceptible
      hemodilaysis patients.
AB  - INTRODUCTION: Intra-dialytic hypotension (IDH) is a common complication during
      hemodialysis (HD) treatment. Previous studies have reported that modulating
      dialysate sodium concentration combined or not with modulation of ultrafiltration
      (UF) rate may reduce the incidence of IDH. The aim of the present study was to
      evaluate the effect of sodium and UF profiles on the occurrence of intra-dialytic
      complications and dialysis quality. METHODS: From a total of 64 patients, we
      selected 18 patients who suffered from recurrent IDH. Every patient received ten
      HD sessions utilizing each of the following treatments: (1) CONTROL: constant
      sodium concentration and UF rates. (2) Sodium and UF profiles: a linearly
      decreasing sodium concentration combined with a linearly decreasing UF rate. (3)
      Sodium profile: decreasing sodium concentration with constant UF rate. RESULTS:
      Fourteen patients completed the study protocol. The incidence of IDH, mean inter
      dialytic weight gain and the delivered dialysis dose were not different between
      the three treatments. However, symptomatic episodes of IDH were more commonand
      pre-dialysis systolic blood pressure was higher during the second and third
      treatment modalities compared to controls. Isolated sodium profile was associated
      with more malaise and less achievement of target session duration compared to the
      other two treatments. Isolated sodium profile was associated with less
      achievement of target UF while combined sodium and UF profiles were associated
      with more achievement of target UF compared to controls. CONCLUSION: Our results
      indicate that sodium profile with or without UF profile does not have a
      beneficial effect on the incidence of IDH, achievement of target session duration
      or the delivered dialysis dose. Keywords : Sodium Profile; Ultrafiltration;
      Intradialytic Complications.

PMID- 22967250
TI  - Active tuberculous infection among adult Sudanese patients on long term
      peritoneal dialysis.
AB  - INTRODUCTION: The prevalence of tuberculosis in Sudan is 209 cases per 100,000
      populations. There are no reports available regarding the prevalence of
      tuberculosis among the end-stage kidney disease and dialysis populations.
      METHODS: We reviewed the medical records of all adults who were on peritoneal
      dialysis (PD) in the Sudan Peritoneal Dialysis Program, during the period from
      June 2005 to December 2011. Those diagnosed as having active tuberculous
      infections were retrospectively studied regarding their demography, clinical
      presentation and outcomes. RESULTS: Out of 350 patients in our program, 19 were
      diagnosed as having active tuberculosis (5.4%). All patients were diagnosed
      during their first year on peritoneal dialysis, 74% were males; the mean age was
      37 +/- 11 years, extrapulmonary tuberculosis was seen in 16/19 (84%) patients and
      it was abdominal in nine of the 16 (47%) patients. In addition to high clinical
      suspicion, the diagnosis of active tuberculosis was supported by tissue biopsy
      findings in 16%, positive polymerase chain reaction in 26%, exudative ascites
      with suggestive radiological features in 21%, strongly positive tuberculin test
      in 21% and a favourable response to empirical antituberculous therapy in 26% of
      patients. HIV test was negative in all 19 patients and only one patient tested
      positive for hepatitis B viral infection. Antituberculous drugs side effects were
      seen in 68% of patients. Forty seven percent of patients showed complete recovery
      and continued on peritoneal dialysis. Our case fatality was 32%. CONCLUSION:
      Abdominal tuberculosis is common among PD patients and its diagnosis should
      always be considered in suspected patients.

PMID- 22967251
TI  - Prevalence of the metabolic syndrome in renal transplant recipients.
AB  - INTRODUCTION: The cause of the metabolic syndrome (MS) is incompletely understood
      but represents a complex interaction between genetic, environmental, and
      metabolic factors, clearly including diet, and level of physical activity. The
      prevalence of MS is continuously increasing in the general population. Recently
      it has been found that MS is also common in renal transplant recipients (RTRs).
      The aim of this study was to determine the prevalence and characteristics of MS
      in a group of Libyan renal transplant recipients, using two different diagnostic
      criteria. METHODS: This study was conducted at the Nephrology Department of the
      National Heart Center, Tripoli, Libya. We determined the prevalence of MS in a
      group of renal transplant recipients using both the National Cholesterol
      Education Program Adult Treatment Panel III (NCEP-ATP III) criteria and the
      International Diabetes Federation (IDF) criteria. All patients were more than six
      months post transplantation. Patients with Pre-transplant diabetes mellitus were
      excluded from the analysis. RESULTS: By using the NCEP-ATP III criteria 26 out of
      91 patients (28.6%) had the metabolic syndrome. MS was commoner in females than
      males, affecting 12 out of 35 females (34.3%) and 14 out of 56 males (25%). Using
      the IDF criteria the metabolic syndrome was diagnosed in 23 patients (25.3%). In
      this group of patients the most common component of the metabolic syndrome was
      high blood pressure and the least common was impaired glucose tolerance and
      diabetes. CONCLUSIONS: The prevalence of MS in our renal transplant patients is
      high, affecting females more than males. Key words: International Diabetes
      Federation; Metabolic Syndrome; NCEP-ATP III; Renal Transplant Recipients.

PMID- 22967252
TI  - Prevalence of HCV infections among hemodialysis patients in Al Gharbiyah
      Governorate, Egypt.
AB  - INTRODUCTION: Hepatitis C virus (HCV) is a significant problem for patients
      undergoing hemodialysis (HD) treatment. This medical problem has never been
      studied in Al Gharbiyah Governorate; this study was conducted aiming to estimate
      the prevalence of anti-HCV positive patients and the incidence of seroconversion
      in its different HD units. METHODS: All 2351 patients maintained on HD in the
      eight towns of Al Gharbiyah Governorate were interviewed and their anti-HCV
      status was tested by a third-generation enzyme immunoassay. Patients who tested
      negative for anti-HCV at the start of the study were re-assessed monthly for HCV
      seroconversion and at the end of the study all patients were screened for HCV
      antibodies. RESULTS: At the start of our study in March 2011, we found that 824
      out of 2351 patients (35%) were anti-HCV reactive. At the end of study in
      November 2011, we found that HCV seroconversion occurred in 168 out of 1527
      patients (11%) who were HCV free at the start of the study. By the end of the
      study, a total of 42.2% were found to be anti-HCV reactive. CONCLUSION: The study
      demonstrated high prevalence of anti-HCV in HD units in Al Gharbiyah Governorate.
      Similar studies must be conducted in all Egyptian governorates' HD units to
      evaluate this major health problem all over Egypt. We also encourage strict
      application of preventive strategies for HCV infection in all health institutes,
      especially HD units. KEYWORDS: Egypt; HCV; Hemodialysis; Seroconversion.

PMID- 22967253
TI  - Rheumatic heart disease associated with secondary renal amyloidosis.
AB  - INTRODUCTION: Amyloidosis is a disorder of protein folding in which normally
      soluble proteins undergo conformational changes and are deposited in the
      extracellular space in an abnormal fibrillar form. Accumulation of these fibrils
      causes progressive disruption of the structure and function of tissues and
      organs, and the systemic forms of amyloidosis are frequently fatal. The
      conditions that underlie amyloid deposition may be either acquired or hereditary.
      Amyloid-A (AA) amyloidosis is the most common form of systemic amyloidosis
      worldwide, AA amyloidosis occurs in the course of chronic inflammatory diseases,
      hereditary periodic fevers, and with certain neoplasms such as Hodgkin disease
      and renal cell carcinoma. Amyloidosis due to rheumatic heart disease (RHD) is not
      common but can be seen. We report here a patient with RHD and AA renal
      amyloidosis. CASE REPORT: we present a 30 year-old Egyptian male with a history
      of RHD, accidently discovered to have nephrotic range proteinuria and rising
      serum creatinine. Serology studies were negative or normal, including antinuclear
      antibody (ANA) and antineutrophil cytoplasmic antibody (ANCA). C3 and C4
      complement levels were normal. Kidney biopsy revealed AA renal amyloidosis. CT
      chest and abdomen revealed bilateral hilar and mediastinal lymphadenopathy and
      para-aortic lymph nodes. Endobronchial biopsy and bronchoalveolar lavage revealed
      non-specific chronic inflammatory changes. The patient's secondary amyloidosis
      was presumed to be related to the long standing RHD after exclusion of other
      causes of secondary amyloidosis. The patient finally died due to heart failure
      and acute pulmonary edema. CONCLUSION: Long standing RHD can lead to secondary AA
      amyloidosis.

PMID- 22967254
TI  - Scleroderma renal crisis precipitated by steroid treatment in systemic lupus
      erythematosus and scleroderma overlap syndrome.
AB  - INTRODUCTION: Connective tissue disorders can overlap in various ways. Patients
      may present with features of more than one specific disease without satisfying
      the diagnostic criteria and thereafter evolve into a specific disease entity.
      Occasionally, patients may fulfil simultaneously the diagnostic criteria of two
      or more diseases. Several cases of systemic sclerosis (SSc) and systemic lupus
      erythematosus (SLE) overlap syndrome have been reported. SLE patients often
      develop lupus nephritis, the treatment of which is based on immunosuppression
      with corticosteroids (CS) and cytotoxic drugs. However, the use of high dose of
      CS has been associated with scleroderma renal crisis (SRC) in patient with SSc.
      CASE REPORT: a 43-year-old woman presented to the nephrology department of the
      Military hospital in Rabat, Morocco, in August 2011 with progressive dyspnea and
      oliguria. She was diagnosed as SLE and scleroderma overlap syndrome based on
      clinical and serological markers. Renal biopsy showed lupus nephritis.
      Immunosuppression consisting of high-dose steroid and cyclophosphamide pulses was
      given. There was response to treatment but 15 days later the course of the
      disease was complicated by scleroderma renal crisis evidenced by elevated blood
      pressure, deteriorating kidney function, hemolysis and thrombocytopenia. The
      patient was treated with perindopril and rapid reduction of steroid doses. This
      was followed by correction of hemolysis and thrombocytopenia. Two months later,
      the patient was off dialysis, but had chronic renal insufficiency with an
      estimated GFR of 25 ml/minute. CONCLUSION: This report describes the occurrence
      of SRC in a patient with lupus nephritis and SSc/ SLE overlap syndrome who was
      treated by CS and cyclophosphamide.

PMID- 22967255
TI  - Acute renal failure following the Saharan horned viper (Cerastes cerastes) bite.
AB  - INTRODUCTION: The Saharan horned viper (Cerastes cerastes) is a common snake in
      the sandy and rocky regions in the south of Morocco. Although nearly all snakes
      with medical relevance can induce acute renal failure (ARF), it's unusual except
      with bites by some viper species. ARF has very rarely been reported following
      Cerastes cerastes bite. CASE REPORT: A 55-year-old Moroccan man was bitten on his
      right hand by a Saharan horned viper, Cerastes cerastes. He presented 24 hours
      later in a state of confusion, agitation and hypotension with marked swelling of
      his right hand. Investigations revealed evidence of disseminated intravascular
      coagulation (DIC) and rhabdomyolysis. The appropriate antivenom was not
      available. Despite adequate hydration, he developed acute renal failure
      necessitating prolonged hemodialysis. He subsequently improved and was discharged
      from the hospital after four weeks with normal renal function. CONCLUSION:
      Although uncommon, the bite of Cerastes cerastes can result in ARF due to DIC and
      rhabdomyolysis. The appropriate antivenom should be made available in areas where
      this snake is prevalent.

PMID- 22967256
TI  - Posterior reversible encephalopathy syndrome in a child with steroid sensitive
      nephrotic syndrome.
AB  - INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) was described
      in adults more than children. It was reported in cases of nephrotic syndrome
      which were mainly on immunosuppressant medications or had severe hypertension.
      CASE REPORT: We report the case of a 9-years old girl who presented with
      nephrotic syndrome and moderate hypertension. Nine days after the initiation of
      steroid therapy she developed disturbed level of consciousness and generalized
      tonic clonic seizures. Her blood pressure was 145/90 mm Hg and she had normal
      serum creatinine and electrolytes levels. She was treated with furosemide and
      convulsions were controlled. After regaining consciousness, the patient
      complained of loss of vision. Fundal examination was normal. Magnetic resonant
      imaging, axial FLAIR images and diffusion weighted imaging showed hyper-intensity
      signal in the parietooccipital areas. Magnetic resonant arteriography and
      spectroscopy excluded ischemic insults and neoplastic process. She regained full
      consciousness and normal vision and was discharged from the ICU four days later.
      PRES was diagnosed based on the typical pattern of brain imaging and the
      reversibility of symptoms. CONCLUSION: Nephrotic syndrome in children should be
      considered a risk factor for developing PRES even without the use of
      immunosuppressant agents or high doses of steroid.

PMID- 22967257
TI  - A Streptococcus iniae DNA vaccine delivered by a live attenuated Edwardsiella
      tarda via natural infection induces cross-genus protection.
AB  - Edwardsiella tarda and Streptococcus iniae are important fish pathogens. We have
      reported previously a live E. tarda vaccine based on the attenuated strain TX5RM
      and a S. iniae DNA vaccine based on the antigen Sia10. In this study, we examined
      the possibility of constructing a cross-genus vaccine by taking advantage of the
      residual infectivity of TX5RM and using it as a carrier host for the natural
      delivery of a S. iniae DNA vaccine. For this purpose, the recombinant TX5RM,
      TX5RMS10, was created, which harbours and retains stably the DNA vaccine plasmid
      pCS10 that expresses Sia10. When flounder were vaccinated with TX5RMS10 via oral
      and immersion routes, TX5RMS10 was detected in multiple tissues within 12-14days
      postvaccination (p.v.). At 7 and 14 days p.v., expression of the DNA vaccine was
      detected in spleen, kidney and liver. Following E. tarda and S. iniae challenge
      at one and 2months p.v., the vaccinated fish exhibited relative per cent survival
      rates of 69-83%. Immunological analysis indicated that TX5RMS10-vaccinated fish
      produced specific serum antibodies and exhibited enhanced expression of a wide
      range of immune genes.

PMID- 22967258
TI  - Genomic scan for single nucleotide polymorphisms reveals patterns of divergence
      and gene flow between ecologically divergent species.
AB  - Recent advances in population genomics have triggered great interest in the
      genomic landscape of divergence in taxa with 'porous' species boundaries. One
      important obstable of previous studies of this topic was the low genomic coverage
      achieved. This issue can now be overcome by the use of 'next generation' or short
      read DNA-sequencing approaches capable of assaying many thousands of single
      nucleotide polymorphisms (SNPs) in divergent species. We have scanned the
      'porous' genomes of Populus alba and Populus tremula, two ecologically divergent
      hybridizing forest trees, using >38,000 SNPs assayed by restriction site
      associated DNA (RAD) sequencing. Windowed analyses indicate great variation in
      genetic divergence (e.g. the proportion of fixed SNPs) between species, and these
      results are unlikely to be strongly biased by genomic features of the Populus
      trichocarpa reference genome used for SNP calling. Divergence estimates were
      significantly autocorrelated (P < 0.01; Moran's I up to 0.6) along 11 of 19
      chromosomes. Many of these autocorrelations involved low divergence blocks, thus
      suggesting that allele sharing was caused by recurrent gene flow rather than
      shared ancestral polymorphism. A conspicuous low divergence block of three
      megabases was detected on chromosome XIX, recently put forward as an incipient
      sex chromosome in Populus, and was largely congruent with introgression of mapped
      microsatellites in two natural hybrid zones (N > 400). Our results help explain
      the origin of the 'genomic mosaic' seen in these taxa with 'porous' genomes and
      suggest rampant introgression or extensive among-species conservation of an
      incipient plant sex chromosome. RAD sequencing holds great promise for detecting
      patterns of divergence and gene flow in highly divergent hybridizing species.

PMID- 22967259
TI  - High one year mortality in adults with sickle cell disease and end-stage renal
      disease.
AB  - Adequate pre-dialysis care reduces mortality among end-stage renal disease (ESRD)
      patients. We tested the hypothesis that individuals with ESRD due to sickle cell
      disease (SCD-ESRD) receiving pre-ESRD care have lower mortality compared to
      individuals without pre-ESRD care. We examined the association between mortality
      and pre-ESRD care in incident SCD-ESRD patients who started haemodialysis between
      1 June, 2005 and 31 May, 2009 using data provided by the Centers for Medicare and
      Medicaid Services (CMS). SCD-ESRD was reported for 410 (0.1%) of 442 017
      patients. One year after starting dialysis, 108 (26.3%) patients with incident
      ESRD attributed to SCD died; the hazard ratio (HR) for mortality among patients
      with SCD-ESRD compared to those without SCD as the primary cause of renal failure
      was 2.80 (95% confidence interval [CI] 2.31-3.38). Patients with SCD-ESRD
      receiving pre-dialysis nephrology care had a lower death rate than those with SCD
      ESRD who did not receive pre-dialysis nephrology care (HR = 0.67, 95% CI 0.45
      0.99). The one-year mortality rate following an ESRD diagnosis was almost three
      times higher in individuals with SCD when compared to those without SCD but with
      ESRD and could be attenuated by pre-dialysis nephrology care.

PMID- 22967260
TI  - Female sex work and international sport events - no major changes in demand or
      supply of paid sex during the 2010 Soccer World Cup: a cross-sectional study.
AB  - BACKGROUND: Important unanswered questions remain on the impact of international
      sporting events on the sex industry. Speculation about increased demand and
      supply of sex work often generates significant attention, but also additional
      funding for HIV programmes. This study assessed whether changes occurred in the
      demand and supply of paid sex during the 2010 Soccer World Cup in South Africa.
      METHODS: Trained sex worker interviewers conducted face-to-face semi-structured
      interviews among consenting female sex workers during May-September 2010. Using
      bivariate analyses we compared supply, demand, sexual risk-taking, and police and
      health services contact pre-World Cup, to levels during the World Cup and after
      the event. RESULTS: No increases were detected in indicators of sex work supply,
      including the proportion of sex workers newly arrived in the city (< 2.5% in each
      phase) or those recently entering the trade (<= 1.5%). Similarly, demand for sex
      work, indicated by median number of clients (around 12 per week) and amount
      charged per transaction ($13) remained similar in the three study periods. Only a
      third of participants reported observing any change in the sex industry ascribed
      to the World Cup. Self-reported condom-use with clients remained high across all
      samples (> 92.4% in all phases). Health-care utilisation decreased non
      significantly from the pre- to during World Cup period (62.4% to 57.0%; P =
      0.075). Across all periods, about thirty percent of participants had interacted
      with police in the preceding month, two thirds of whom had negative interactions.
      CONCLUSIONS: Contrary to public opinion, no major increases were detected in the
      demand or supply of paid sex during the World Cup. Although the study design
      employed was unable to select population-based samples, these findings do not
      support the public concern and media speculation prior to the event, but rather
      signal a missed opportunity for public health action. Given the media attention
      on sex work, future sporting events offer strategic opportunities to implement
      services for sex workers and their clients, especially as health service
      utilisation might decrease in this period.

PMID- 22967261
TI  - HT-2 toxin 4-glucuronide as new T-2 toxin metabolite: enzymatic synthesis,
      analysis, and species specific formation of T-2 and HT-2 toxin glucuronides by
      rat, mouse, pig, and human liver microsomes.
AB  - Glucuronides of the mycotoxin T-2 toxin and its phase I metabolite HT-2 toxin are
      important phase II metabolites under in vivo and in vitro conditions. Since
      standard substances are essential for the direct quantitation of these
      glucuronides, a method for the enzymatic synthesis of T-2 and HT-2 toxin
      glucuronides employing liver microsomes was optimized. Structure elucidation by
      nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry revealed that
      besides T-2 toxin glucuronide and HT-2 toxin 3-glucuronide also the newly
      identified isomer HT-2 toxin 4-glucuronide was formed. Glucuronidation of T-2 and
      HT-2 toxin in liver microsomes of rat, mouse, pig, and human was compared and
      metabolites were analyzed directly by liquid chromatography coupled with tandem
      mass spectrometry (LC-MS/MS). A distinct, species specific pattern of
      glucuronidation of T-2 and HT-2 toxin was observed with interesting
      interindividual differences. Until recently, glucuronides have frequently been
      analyzed indirectly by quantitation of the aglycone after enzymatic cleavage of
      the glucuronides by beta-glucuronidase. Therefore, the hydrolysis efficiencies of
      T-2 and HT-2 toxin glucuronides using beta-glucuronidases from Helix pomatia,
      bovine liver, and Escherichia coli were compared. 

PMID- 22967263
TI  - Adequate or not? A comparison of 24-hour urine studies for renal stone prevention
      by creatinine to weight ratio.
AB  - PURPOSE: The intent of this study was to compare urine parameters between kidney
      stone formers with low, expected, and high creatinine to weight ratio (Cr/kg) and
      to discuss implications for treatment. PATIENTS AND METHODS: In this
      retrospective study, 381 stone formers (205 females and 176 males) with urine
      collections for nephrolithiasis evaluation were included. Using the first
      collected sample, patients were grouped into low, expected, and high Cr/kg using
      sex appropriate reference ranges (15.0-20.0 mg/kg for females and 18.0-24.0 mg/kg
      for males) and evaluated. RESULTS: Of initial collections, 50.7% were outside the
      Cr/kg reference range. Median age increased as Cr/kg decreased with 13 years age
      difference between low (56) and high (43) groups. Body mass index and weight also
      increased significantly with decreased ratio. No significant difference between
      groups was found for urine volume, total oxalate, oxalate concentration, pH, and
      supersaturations of calcium oxalate and uric acid. Total calcium, sodium,
      citrate, calcium concentration, supersaturation of calcium phosphate, and other
      parameters significantly increased with increased Cr/kg for the cohort.
      CONCLUSIONS: To our knowledge, this is the first study to thoroughly evaluate the
      impact of Cr/kg on urine parameters. Clinicians should be cognizant of
      limitations of Cr/kg for evaluating collection adequacy. It is especially
      important to consider Cr/kg when there is potential for undertreatment or
      overtreatment of patients with abnormal Cr/kg. Studies demonstrating
      hypercalciuria and high Cr/kg may need to be repeated before starting thiazide
      diuretics. Further studies are needed to determine how to better interpret urine
      components that vary with Cr/kg ratio.

PMID- 22967262
TI  - A dual-column solid phase extraction strategy for online collection and
      preparation of continuously flowing effluent streams for mass spectrometry.
AB  - Current desalination techniques for mass spectrometry-based protocols are
      problematic for performing temporal response studies where increased temporal
      resolution requires small samples and faster sampling frequencies, which greatly
      increases the number of samples and sample preparation time. These challenges are
      pertinent to cellular dynamics experiments, where it is important to sample the
      biological system frequently and with as little sample waste as possible. To
      address these needs, we present a dual-column online solid phase extraction (SPE)
      approach capable of preconcentrating and preparing a constantly perfusing sample
      stream, with minimal to no sample loss. This strategy is evaluated for use in
      microfluidic bioreactor studies specifically aimed at characterizing suitable
      sample flow rates, temporal resolving power, and analyte concentrations. In this
      work, we demonstrate that this strategy may be used for flow rates as low as 500
      nL/min, with temporal resolving power on the order of 3 min, with analyte
      loadings ranging from femtomoles to picomoles for metabolites. Under these
      conditions, recoveries of ca. 80% are obtained even at femtomole loadings.

PMID- 22967264
TI  - Hypertension: development of a prediction model to adjust self-reported
      hypertension prevalence at the community level.
AB  - BACKGROUND: Accurate estimates of hypertension prevalence are critical for
      assessment of population health and for planning and implementing prevention and
      health care programs. While self-reported data is often more economically
      feasible and readily available compared to clinically measured HBP, these reports
      may underestimate clinical prevalence to varying degrees. Understanding the
      accuracy of self-reported data and developing prediction models that correct for
      underreporting of hypertension in self-reported data can be critical tools in the
      development of more accurate population level estimates, and in planning
      population-based interventions to reduce the risk of, or more effectively treat,
      hypertension. This study examines the accuracy of self-reported survey data in
      describing prevalence of clinically measured hypertension in two racially and
      ethnically diverse urban samples, and evaluates a mechanism to correct self
      reported data in order to more accurately reflect clinical hypertension
      prevalence. METHODS: We analyze data from the Detroit Healthy Environments
      Partnership (HEP) Survey conducted in 2002 and the National Health and Nutrition
      Examination (NHANES) 2001-2002 restricted to urban areas and participants 25
      years and older. We re-calibrate measures of agreement within the HEP sample
      drawing upon parameter estimates derived from the NHANES urban sample, and assess
      the quality of the adjustment proposed within the HEP sample. RESULTS: Both self
      reported and clinically assessed prevalence of hypertension were higher in the
      HEP sample (29.7 and 40.1, respectively) compared to the NHANES urban sample
      (25.7 and 33.8, respectively). In both urban samples, self-reported and
      clinically assessed prevalence is higher than that reported in the full NHANES
      sample in the same year (22.9 and 30.4, respectively). Sensitivity, specificity
      and accuracy between clinical and self-reported hypertension prevalence were
      'moderate to good' within the HEP sample and 'good to excellent' within the
      NHANES sample. Agreement between clinical and self-reported hypertension
      prevalence was 'moderate to good' within the HEP sample (kappa =0.65; 95% CI =
      0.63-0.67), and 'good to excellent' within the NHANES sample (kappa = 0.75; 95%CI
      = 0.73-0.80). Application of a 'correction' rule based on prediction models for
      clinical hypertension using the national sample (NHANES) allowed us to re
      calibrate sensitivity and specificity estimates for the HEP sample. The adjusted
      estimates of hypertension in the HEP sample based on two different correction
      models, 38.1% and 40.5%, were much closer to the observed hypertension prevalence
      of 40.1%. CONCLUSIONS: Application of a simple prediction model derived from
      national NHANES data to self-reported data from the HEP (Detroit based) sample
      resulted in estimates that more closely approximated clinically measured
      hypertension prevalence in this urban community. Similar correction models may be
      useful in obtaining more accurate estimates of hypertension prevalence in other
      studies that rely on self-reported hypertension.

PMID- 22967265
TI  - Synthesis of indolylquinolines, indolylacridines, and
      indolylcyclopenta[b]quinolines from the Baylis-Hillman adducts: an in situ [1,3]
      sigmatropic rearrangement of an indole nucleus to access indolylacridines and
      indolylcyclopenta[b]quinolines.
AB  - A simple and easy route to the synthesis of a variety of structurally diverse
      indolylquinolines, indolylacridines, and indolylcyclopenta[b]quinoline
      derivatives via the reductive cyclization of C-alkylated indole derivatives,
      derived from acyclic as well as cyclic Baylis-Hillman adducts with indoles, is
      described. An unusual in situ [1,3]-sigmatropic rearrangement of the indole
      nucleus was observed during the reductive cyclicization of alpha-regioselective B
      H adducts containing indoles to produce indolylacridines and
      indolylcyclopenta[b]quinoline derivatives.

PMID- 22967266
TI  - Impact of central venous pressure on cardiorenal interactions in adult patients
      with congenital heart disease after biventricular repair.
AB  - BACKGROUND: Cardiorenal interactions adversely impact the prognosis in heart
      failure patients an effect which crucially involves increased central venous
      pressure (CVP). However, it is unclear whether the same pathophysiology operates
      in adults with congenital heart disease (CHD). PURPOSE: The present study was
      designed to assess cardiorenal interactions in adults with CHD after
      biventricular repair. METHODS AND RESULTS: We measured the kidney length (KL,
      cm/m) and renal resistive index (RI) in 77 consecutive patients and 30 controls.
      We also measured hemodynamics, plasma B-type natriuretic peptide level, 24-hour
      creatinine clearance, and peak oxygen uptake in each patient. The CVP correlated
      with the KL (r = 0.44, P <.001) and the RI was greater in the patients (P
      <.0001). The high RI was independently determined by the CVP, aortic pressure,
      and cardiac index (P <.05-.001), and correlated with the 24-hour creatinine
      clearance (r = -0.30, P <.05). The RI correlated closely with the neurohumoral
      activations and peak oxygen uptake (|r| = 0.45-0.50, P <.0001), and the patients
      with a traditional criteria of high RI (>=0.70) had a higher incidence of
      cardiovascular events that required unscheduled hospitalization (hazard ratio =
      2.78, 95% confidence interval 1.26-6.10, P <.05). Multivariate Cox model with the
      cutoff values of KL >=68 cm/m and RI >=0.74 revealed that a greater KL (hazard
      ratio = 4.03, 95% confidence interval 1.46-11.1, P <.01) as well as B-type
      natriuretic peptide (P <.001) independently predicted the events. CONCLUSIONS:
      Hemodynamics, especially a high CVP, independently predicted the enlarged kidney
      and abnormal intrarenal flow dynamics that are closely associated with heart
      failure severity and cardiovascular events in adults with CHD after biventricular
      repair.

PMID- 22967267
TI  - Self-assembly of gemini surfactants: a computer simulation study.
AB  - The self-assembly behavior of gemini (dimeric or twin-tail) dicarboxylate
      disodium surfactants is studied using molecular dynamics simulations. A united
      atom model is employed for the surfactants with fully atomistic counterions and
      water. This gemini architecture, in which two single tailed surfactants are
      joined through a flexible hydrophobic linker, has been shown to exhibit
      concentration-dependent aqueous self-assembly into lyotropic phases including
      hexagonal, gyroid, and lamellar morphologies. Our simulations reproduce the
      experimentally observed phases at similar amphiphile concentrations in water,
      including the unusual ability of these surfactants to form gyroid phases over
      unprecedentedly large amphiphile concentration windows. We demonstrate
      quantitative agreement between the predicted and experimentally observed domain
      spacings of these nanostructured materials. Through careful conformation analyses
      of the surfactant molecules, we show that the gyroid phase is electrostatically
      stabilized related to the lamellar phase. By starting with a lamellar phase, we
      show that use of a bulkier N(CH(3))(4)(+) counterion in place of Na(+) drives the
      formation of a gyroid phase. Decreasing the charge on the surfactant headgroups
      by carboxylate protonation decreases the degree of order in the lamellar phase.
      Using our models, we show that the translational diffusion of water and the Na(+)
      counterions is decreased by several orders of magnitude over the studied
      concentration range, and we attribute these effects to strong correlations
      between the mobile species and the surfactant headgroups.

PMID- 22967268
TI  - A new direction in dye-sensitized solar cells redox mediator development: in situ
      fine-tuning of the cobalt(II)/(III) redox potential through Lewis base
      interactions.
AB  - Dye-sensitized solar cells (DSCs) are an attractive renewable energy technology
      currently under intense investigation. In recent years, one area of major
      interest has been the exploration of alternatives to the classical
      iodide/triiodide redox shuttle, with particular attention focused on cobalt
      complexes with the general formula [Co(L)(n)](2+/3+). We introduce a new approach
      to designing redox mediators that involves the application of
      [Co(PY5Me(2))(MeCN)](2+/3+) complexes, where PY5Me(2) is the pentadentate ligand,
      2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine. It is shown, by X-ray crystallography,
      that the axial acetonitrile (MeCN) ligand can be replaced by more strongly
      coordinating Lewis bases (B) to give complexes with the general formula
      [Co(PY5Me(2))(B)](2+/3+), where B = 4-tert-butylpyridine (tBP) or N
      methylbenzimidazole (NMBI). These commonly applied DSC electrolyte components are
      used for the first time to fine-tune the potential of the redox couple to the
      requirements of the dye through coordinative interactions with the Co(II/III)
      centers. Application of electrolytes based on the [Co(PY5Me(2))(NMBI)](2+/3+)
      complex in combination with a commercially available organic sensitizer has
      enabled us to attain DSC efficiencies of 8.4% and 9.2% at a simulated light
      intensity of 100% sun (1000 W m(-2) AM1.5 G) and at 10% sun, respectively, higher
      than analogous devices applying the [Co(bpy)(3)](2+/3+) redox couple, and an open
      circuit voltage (V(oc)) of almost 1.0 V at 100% sun for devices constructed with
      the tBP complex.

PMID- 22967269
TI  - Isothermal microcalorimetry provides new insights into biofilm variability and
      dynamics.
AB  - The purpose of this study was to investigate a three-species in vitro biofilm
      with peri-implantitis-related bacteria for its variability and metabolic
      activity. Streptococcus sanguinis, Fusobacterium nucleatum, and Porphyromonas
      gingivalis were suspended in simulated body fluid containing 0.2% glucose to form
      biofilms on polished, protein-coated implant-grade titanium disks over 72 h using
      a flow chamber system. Thereafter, biofilm-coated disks were characterized by
      scanning electron microscopy and fluorescence in situ hybridization/confocal
      laser scanning microscopy. To assess metabolic activity within the biofilms,
      their heat flow was recorded for 480 h at 37  degrees C by IMC. The microscopic
      methods revealed that the total number of bacteria in the biofilms varied
      slightly among specimens (2.59 * 10(4)  +/- 0.67 * 10(4)  cells mm(-2) ), whereas
      all three species were found constantly with unchanged proportions (S. sanguinis
      41.3 +/- 4.8%, F. nucleatum 17.7 +/- 2.1%, and P. gingivalis 41.0 +/- 4.9%). IMC
      revealed minor differences in time-to-peak heat flow (20.6 +/- 4.5 h), a trend
      consistent with the small variation in bacterial species proportions as shown by
      microscopy. Peak heat flow (35.8 +/- 42.6 MUW), mean heat flow (13.1 +/- 22.0
      MUW), and total heat over 480 h (23.5 +/- 37.2 J) showed very high variation.
      These IMC results may be attributed to differences in the initial cell counts and
      relative proportions of the three species, their distribution and embedment in
      exopolysaccharide matrix on the test specimens. The present results provide new
      insights into variability and dynamics of biofilms on titanium disks, aspects
      that should be explored in future studies of dental surfaces.

PMID- 22967271
TI  - Q fever endocarditis associated with a cardiovascular implantable electronic
      device.
AB  - Cardiovascular implantable electronic devices (CIEDs) are frequently related to
      endocarditis. Most cases of intravascular CIED infections are usually related to
      skin flora, but a few cases may occur with negative blood culture. Coxiella
      burnetii is one of the main causes of blood culture-negative endocarditis in
      native and prosthetic valves, but to date no cases related to CIED have been
      published. Herein we report two cases of Q fever endocarditis related to these
      non-valvular cardiovascular devices.

PMID- 22967270
TI  - Inhibition of Nogo-66 receptor 1 enhances recovery of cognitive function after
      traumatic brain injury in mice.
AB  - Central nervous system (CNS) axons recover poorly following injury because of the
      expression of myelin-derived inhibitors of axonal outgrowth such as Nogo, myelin
      associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp),
      all of which bind to the Nogo-66 receptor 1 (NgR1). Herein we examine the role of
      NgR1 in the recovery of motor and cognitive function after traumatic brain injury
      (TBI) using a controlled cortical impact (CCI) model in NgR1 knockout (KO) and
      wild-type (WT) mice. Four weeks post-injury, scores on the Novel Object
      Recognition test were significantly increased in NgR1 KO mice compared with WT
      mice (p<0.05), but motor behavior test scores did not differ significantly
      between the two groups. Nissl staining showed that NgR1 KO mice had less brain
      injury volume 2 weeks after CCI (p<0.05). Histological analysis revealed more
      doublecortin (DCX+) cells (p<0.01) and more Ki-67+ cells in the contralateral
      dentate gyrus (DG) (p<0.05) 2 weeks after CCI in NgR1 KO mice than in WT.
      Furthermore, DCX+ cells still retained their longer processes in KO mice (p<0.01)
      4 weeks following trauma. The number of bromodeoxyuridine (BrdU)+ cells did not
      differ between the two groups at 4 weeks post-trauma, but KO mice had higher
      numbers of cells that co-stained with NeuN, a marker of mature neurons. Increased
      transcription of growth-associated protein (GAP)-43 in both the injured and
      contralateral sides of the hippocampus (both p<0.05) was detected in NgR1 KO mice
      relative to WT. These data suggest that NgR1 negatively influences plasticity and
      cognitive recovery after TBI.

PMID- 22967272
TI  - Assessment of the endothelial functions in monocrotaline-induced pulmonary
      hypertension.
AB  - Pulmonary hypertension (PH) is a life-threatening disease that causes endothelial
      dysfunction in the pulmonary vascular bed. Systemic endothelial dysfunction has
      also been reported in PH. This study compared the systemic and pulmonary vascular
      responses and some blood biomarkers of endothelial function in monocrotaline
      (MCT)-induced PH of rats. It also investigated the effect of sildenafil and
      iloprost treatment. MCT application induced elevation in the right ventricular
      pressures of the rat heart that had been reversed by sildenafil and iloprost
      treatment. Acetylcholine-induced endothelium-dependent relaxations of the
      isolated pulmonary artery were decreased in the PH group and this failure was
      reversed by sildenafil and iloprost treatment. Acetylcholine-induced endothelium
      dependent relaxations of the isolated thoracic aorta were similar in all groups.
      Serotonin-induced contractions of the pulmonary artery were augmented by PH. In
      the isolated aorta, serotonin-stimulated contraction was not different in the
      control and MCT groups, but sildenafil and iloprost treatment decreased serotonin
      responses. The nitric oxide (NO) level in systemic circulation was not
      significantly changed by PH. However, sildenafil and iloprost treatments caused a
      decrease in the plasma level of NO. Asymmetric dimethylarginine levels in plasma
      were significantly decreased after MCT application and were not recovered by
      sildenafil and iloprost treatment. Total antioxidant capacity and H2S level of
      plasma were similar in all groups. Results of this study showed that MCT-induced
      PH caused specific toxic effects on pulmonary vasculature without any functional
      effects on the aorta. In addition, it was also demonstrated that sildenafil and
      iloprost treatments were effective in the MCT-induced PH.

PMID- 22967273
TI  - Complete gallbladder torsion diagnosed with sequential computed tomography scans:
      a case report.
AB  - INTRODUCTION: Torsion of the gallbladder is an extremely rare cause of acute
      abdomen, which commonly affects thin elderly women. A prompt surgical approach is
      necessary to avoid fatal complications associated with gangrene and perforation
      of the gallbladder. However, it is difficult to make a preoperative diagnosis
      using ordinary imaging modalities. CASE PRESENTATION: An 84-year-old Japanese
      woman was admitted to our hospital due to left lower abdominal pain. Her pain
      shifted suddenly to the right upper abdomen a half day after admission. Although
      her enlarged and wall-thickened gallbladder had been already seen at admission,
      it rotated approximately 180 degrees and deviated to the midline of her abdomen
      on the second computed tomography scan, which helped us to make a correct
      diagnosis of gallbladder torsion. The patient underwent an emergency operation
      (detorsion and cholecystectomy) and recovered without any complications. The
      gallbladder had necrosis due to torsion. CONCLUSION: Sequential diagnostic
      imaging might be helpful to make a preoperative diagnosis of gallbladder torsion
      when the gallbladder is enlarged and wall thickened but the patient does not
      present with typical clinical symptoms.

PMID- 22967274
TI  - Sr2Mn3Sb2O2 type oxyselenides: structures, magnetism, and electronic properties
      of Sr2AO2M2Se2 (A=Co, Mn; M=Cu, Ag).
AB  - Four new oxyselenides with nominal formula Sr(2)AO(2)M(2)Se(2) (A=Co, Mn; M=Cu,
      Ag) have been synthesized. They all crystallize in an I4/mmm space group and
      consist of alternating perovskite-like (Sr(2)AO(2))(2+) blocks and antiflourie
      (M(2)Se(2))(2-) layers, which are relatively rare layered oxyselenides reported
      so far that are isostructural to Sr(2)Mn(3)Sb(2)O(2). From powder X-ray
      diffraction data, compounds Sr(2)CoO(2)Cu(2)Se(2) and Sr(2)CoO(2)Ag(2)Se(2) are
      found near stoichiometric, whereas Sr(2)MnO(2)Cu(2-delta)Se(2) and
      Sr(2)MnO(2)Ag(2-delta)Se(2) possess substantial copper or silver vacancies
      (delta~0.5), consistent with their oxysulfide analogues. X-ray photoelectron
      spectroscopy measurements indicate the readily oxidization of Mn(2+) ions should
      be responsible for the occurrence of Cu/Ag vacancies. The rigid (Sr(2)AO(2))(2+)
      blocks within these compounds constrain the basal lattice parameters in the ab
      plane and result in largely deformed tetrahedral sites for the large silver ions.
      Magnetic susceptibility measurements of Sr(2)CoO(2)M(2)Se(2) (M=Cu, Ag) show
      complex antiferromagnetic transitions, while Sr(2)MnO(2)M(2-delta)Se(2) (M=Cu,
      Ag) show high-temperature Curie-Weiss behavior, followed by low-temperature
      antiferromagnetic transitions at 54 K and 67 K, respectively. Except for
      Sr(2)MnO(2)Ag(2-delta)Se(2), the other three compounds exhibit p-type
      semiconducting transport properties, with the measured resistivities several
      orders lower than their oxysulfide analogues. Hall measurement reveals high
      mobilities of Sr(2)CoO(2)M(2)Se(2) (M=Cu, Ag) compounds at room temperature. The
      unusually small optical band gaps (~0.07 eV) of Sr(2)CoO(2)Cu(2)Se(2),
      Sr(2)CoO(2)Ag(2)Se(2), and Sr(2)MnO(2)Cu(2-delta)Se(2) are also reported.

PMID- 22967275
TI  - Daily associations of alcohol use with sexual behaviour and condom use during
      spring break.
AB  - INTRODUCTION AND AIMS: Spring Break is associated with high levels of alcohol use
      and related consequences, and with risky sexual behaviour, among North American
      college students. However, the extent to which Spring Break drinking and sexual
      behaviours are related has not been well documented. DESIGN AND METHODS:
      Undergraduate students (n = 263) were surveyed prior to and immediately after
      Spring Break, including retrospective reports of daily behaviour for each day of
      Spring Break. RESULTS: Hierarchical linear modelling was used to predict
      penetrative sex and condom use. Binge drinking on a day was associated with a
      greater likelihood of penetrative sex and of condom use, moderated by
      relationship status. Binge drinking led to a greater increase in penetrative sex
      among single students. Single students were more likely to use condoms after
      drinking; those in a relationship were less likely to use condoms after drinking.
      DISCUSSION AND CONCLUSIONS: Single college students are more likely to have sex
      after binge drinking on Spring Break, but also more likely to use condoms after
      drinking, compared to students in a relationship. Intervention efforts may need
      to acknowledge relationship status.

PMID- 22967276
TI  - Relationship between mobility, violence and HIV/STI among female sex workers in
      Andhra Pradesh, India.
AB  - BACKGROUND: Violence and mobility have been identified as critical factors
      contributing to the spread of HIV worldwide. This study aimed to assess the
      independent and combined associations of mobility and violence with sexual risk
      behaviors and HIV, STI prevalence among female sex workers (FSWs) in India.
      METHODS: Data were drawn from a cross-sectional, bio-behavioral survey conducted
      among 2042 FSWs across five districts of southern India in 2005-06. Regression
      models were used to estimate odds ratios and 95% confidence intervals (CIs) for
      sexual risk behaviors and HIV infection based on experience of violence and
      mobility after adjusting for socio-demographic and sex work related
      characteristics. RESULTS: One-fifth of FSWs (19%) reported experiencing violence;
      68% reported travelling outside their current place of residence at least once in
      the past year and practicing sex work during their visit. Mobile FSWs were more
      likely to report violence compared to their counterparts (23% vs. 10%, p <
      0.001). Approximately 1 in 5 tested positive for HIV. In adjusted models, FSWs
      reporting both mobility and violence as compared to their counterparts were more
      likely to be infected with HIV (Adjusted odds ratio (adjusted OR): 2.07, 95% CI:
      1.42-3.03) and to report unprotected sex with occasional (adjusted OR: 2.86, 95%
      CI: 1.76-4.65) and regular clients (adjusted OR: 2.07, 95% CI: 1.40-3.06).
      CONCLUSIONS: The findings indicate that mobility and violence were independently
      associated with HIV infection. Notably, the combined effect of mobility and
      violence posed greater HIV risk than their independent effect. These results
      point to the need for the provision of an enabling environment and safe spaces
      for FSWs who are mobile, to augment existing efforts to reduce the spread of
      HIV/AIDS.

PMID- 22967277
TI  - Choosing a survey sample when data on the population are limited: a method using
      Global Positioning Systems and aerial and satellite photographs.
AB  - BACKGROUND: Various methods have been proposed for sampling when data on the
      population are limited. However, these methods are often biased. We propose a new
      method to draw a population sample using Global Positioning Systems and aerial or
      satellite photographs. RESULTS: We randomly sampled Global Positioning System
      locations in designated areas. A circle was drawn around each location with
      radius representing 20 m. Buildings in the circle were identified from satellite
      photographs; one was randomly chosen. Interviewers selected one household from
      the building, and interviews were conducted with eligible household members.
      CONCLUSIONS: Participants had known selection probabilities, allowing proper
      estimation of parameters of interest and their variances. The approach was made
      possible by recent technological developments and access to satellite
      photographs.

PMID- 22967278
TI  - Interleukin-22 predicts severity and death in advanced liver cirrhosis: a
      prospective cohort study.
AB  - BACKGROUND: Interleukin-22 (IL-22), recently identified as a crucial parameter of
      pathology in experimental liver damage, may determine survival in clinical end
      stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity
      and mortality of patients with advanced liver cirrhosis has not been performed so
      far. METHODS: This is a prospective cohort study including 120 liver cirrhosis
      patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to
      survival and hepatic complications. RESULTS: A total of 71% of patients displayed
      liver cirrhosis-related complications at study inclusion. A total of 23% of the
      patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was
      detectable in 74% of patients but only in 10% of healthy donors (P < 0.001).
      Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal
      syndrome (P < 0.0001), and spontaneous bacterial peritonitis (P = 0.001).
      Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced
      survival compared to patients with regular (<=18 pg/ml) levels of IL-22 (321 days
      versus 526 days, P = 0.003). Other factors associated with reduced overall
      survival were high CRP (>=2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314,
      confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05,
      HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P =
      0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD)
      score >=20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR
      0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards
      analysis identified elevated systemic IL-22 levels as independent predictors of
      reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). CONCLUSIONS: In
      patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for
      reduced survival independently from age, liver-related complications, CRP,
      creatinine and the MELD score. Thus, processes that lead to a rise in systemic
      interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.

PMID- 22967279
TI  - Effect of acute acupuncture treatment on exercise performance and postexercise
      recovery: a systematic review.
AB  - BACKGROUND: Preliminary evidence suggests that acupuncture applied proximally
      during a single bout of exercise can enhance exercise performance and/or expedite
      postexercise recovery. The purpose of this investigation was to review trials,
      systematically and critically, that have investigated such hypotheses and
      delineate areas for future research. METHOD: A systematic review using
      computerized databases was performed. RESULTS: Four trials were found: Three
      involved within-subjects designs and one used a parallel group design. Few
      participants were enrolled (n=10-20). Fourteen acupuncture sites were used across
      the four trials: DU 20, LI 15, LI 13, PC 6, ST 36, SP 6, PC 5, LU 7, LI 4, GB 37,
      GB 39, GB 34, and LI 11, and LR 3. PC 6, and ST 36 were the most commonly used
      sites. Three trials evaluated the effect of acupuncture on exercise performance.
      One of these trials noted that electroacupuncture stimulation of either PC 5 and
      PC 6 or LU 7 and LI4 significantly increased peak power output, blood pressure,
      and rate pressure product (RPP) versus control. However, two trials documented no
      effect of acupuncture on exercise performance using point combinations of either
      DU 20, LI 15, LI 13, PC 6, ST 36, and SP 6 or DU 20, ST 36, GB 34, LI 11, LR 3.
      One trial evaluated the effect of acupuncture on postexercise recovery and found
      that heart rate, oxygen consumption, and blood lactate were significantly reduced
      secondary to acupuncturing of PC 6 and ST 36 versus control and placebo
      conditions at 30 or 60 minutes postexercise. CONCLUSIONS: There is preliminary
      support for the use of acupuncture as a means to enhance exercise performance and
      postexercise recovery, but many limitations exist within this body of literature.
      Adequately powered, RCTs with thorough and standardized reporting of research
      methods (e.g., acupuncture and exercise interventions) and results are required
      to determine more adequately the effect of acupuncture methods on exercise
      performance and postexercise recovery. Future investigations should involve
      appropriate placebo methods and blinding of both participants and investigators.

PMID- 22967280
TI  - Tension Tamer: delivering meditation with objective heart rate acquisition for
      adherence monitoring using a smart phone platform.
AB  - OBJECTIVES: This brief report demonstrates the proof of concept of the Tension
      Tamer (TT) smartphone application, which integrates photoplethysmograph
      capabilities with breathing awareness meditation (BAM), to reduce stress and
      measure heart rate and adherence. DESIGN: Methods for objectively measuring heart
      rate and adherence to BAM were developed as part of a future randomized
      controlled trial. SETTING/LOCATION: The study was conducted at Jerry Zucker
      Middle School of Science and the Medical University of South Carolina,
      Charleston. SUBJECTS: The subjects were three prehypertensive male teachers.
      INTERVENTION: The method used was smartphone delivered BAM. OUTCOME MEASURES:
      Objective measures included heart rate, adherence, and ambulatory blood pressure
      (BP). RESULTS: Adherence data was successfully collected by the TT application.
      Increased adherence to TT coincided with increased improvements in ambulatory BP
      over a 3-month period. CONCLUSIONS: TT shows promise as a simple inexpensive
      program for administering BAM and capturing adherence data in future clinical
      trials.

PMID- 22967281
TI  - Evaluation of the effect of progressive relaxation exercises on fatigue and sleep
      quality in patients with multiple sclerosis.
AB  - BACKGROUND AND OBJECTIVES: Fatigue and sleep problems are very commonly observed
      in patients with multiple sclerosis (MS). The Progressive Muscle Relaxation
      Technique (PMRT), used as one of the alternative methods in recent years, is
      reported to have benefits such as facilitating sleep and reducing sensitivity
      against fatigue. This research was conducted to investigate the effect of PMRT on
      fatigue and sleep quality in patients with MS. SETTING AND DESIGN: This research
      was performed as a single-group pretest/post-test pretrial model. The research
      was conducted between March 2008 and December 2009 in the neurology polyclinic.
      MATERIALS AND METHODS: The study was conducted with 32 patients who met the
      research criteria and agreed to participate in the study. A Personal Information
      Form was used as a data collection tool, Fatigue Severity Scale was used for
      measuring fatigue, and the Pittsburgh Sleep Quality Index was used for evaluating
      the sleep quality. PMRT was applied to the sample group once a day for 6 weeks.
      STATISTICAL ANALYSIS: Percentage, paired t-test, and Pearson's correlation
      analysis were used in the assessment of data. RESULTS: It was determined that
      PMRT decreased patients' fatigue level and improved their sleep quality, and this
      difference was observed to be statistically significant. Moreover, patients'
      fatigue level increased as their sleep quality decreased. CONCLUSIONS: This study
      supports the effect of PMRT on fatigue and sleep quality in patients with MS, and
      it is recommended that further studies be conducted on this subject in the
      future.

PMID- 22967282
TI  - Adverse events following acupuncture: a systematic review of the Chinese
      literature for the years 1956-2010.
AB  - OBJECTIVES: The objective of this study was to make non-Chinese readers better
      informed about the current safety situation of acupuncture in China. METHODS:
      Four (4) major Chinese comprehensive databases were searched: Chinese Journal
      Full-text Database (1949-2010), China Biomedical Literature Database (1978-2010),
      Chinese Technology Journal Database (1989-2010), and Wanfang (1998-2010). Case
      reports of adverse events related to acupuncture therapy were included.
      Literature reviews, case-control study, translations, duplicate literatures in
      various databases, and duplicate published articles with duplicate data were
      excluded. RESULTS: One hundred and sixty-seven (167) articles were included with
      1038 cases, among which 35 patients died. The most frequent adverse events were
      syncope (468 cases), pneumothorax (307 cases), and subarachnoid hemorrhage (64
      cases). CONCLUSIONS: Acupuncture-related adverse events were mainly caused by
      mental tension of the patient, improper operation by the doctor, and
      incompleteness of sterilization. Most of them can be avoided by standardizing
      teaching and clinical practices. Making the corresponding safety standards can
      greatly lower the risk of adverse events and protect patient safety to the
      greatest extent.

PMID- 22967283
TI  - A novel Fe(II)/alpha-ketoglutarate-dependent dioxygenase from Burkholderia
      ambifaria has beta-hydroxylating activity of N-succinyl l-leucine.
AB  - An Fe(II)/alpha-ketoglutarate-dependent dioxygenase, SadA, was obtained from
      Burkholderia ambifaria AMMD and heterologously expressed in Escherichia coli.
      Purified recombinant SadA had catalytic activity towards several N-substituted l
      amino acids, which was especially strong with N-succinyl l-leucine. With the NMR
      and LC-MS analysis, SadA converted N-succinyl l-leucine into N-succinyl l-threo
      beta-hydroxyleucine with >99% diastereoselectivity. SadA is the first enzyme
      catalysing beta-hydroxylation of aliphatic amino acid-related substances and a
      potent biocatalyst for the preparation of optically active beta-hydroxy amino
      acids. 

PMID- 22967284
TI  - Robot-assisted ureteroneocystostomy: technique and comparative outcomes.
AB  - BACKGROUND AND PURPOSE: Ureteroneocystostomy can be used for the treatment of
      patients with a wide variety of ureteral pathology. Over the last decade, robot
      assisted surgery has become more commonly used as a minimally invasive approach
      for reconstructive upper urinary tract procedures. The aim of this study is to
      present our experience with robot-assisted ureteroneocystosctomy (RUNC) with a
      comparison with that of open ureteroneocystostomy (OUNC). PATIENTS AND METHODS:
      Medical records of 25 patients who underwent RUNC and 41 patients who underwent
      OUNC or at our institution between 2000 and 2010 were retrospectively analyzed.
      Perioperative and postoperative data including demographics, surgical outcomes,
      and clinical and radiographic findings at postoperative follow-up were considered
      in the comparative analysis. Descriptive statistics were used to present the
      data. The significance of the difference between variables was evaluated using
      the Wilcoxon rank sum test for continuous and Fisher exact test for categorical
      variables. RESULTS: No significant differences were detected in terms of baseline
      patient characteristics between the two groups. The OUNC procedures were
      performed with a shorter median operative time (200 vs 279 min., P=0.0008),
      whereas RUNC patients had a shorter hospital stay (median 3 vs 5 days, P=0.0004),
      less narcotic pain requirement (morphine equivalent, mg 104.6 vs 290, P=0.0001),
      and less estimated blood loss (100 vs 150 mL, P=<0.0002). There as no significant
      difference in the rate of reoperation between groups: RUNC 2/25 (7.6 %) vs OUNC
      4/41 (9.7%) P=0.8. Limitations include the retrospective nature of the study and
      the difference in indications for surgery. CONCLUSION: RUNC provides excellent
      outcomes with shorter hospital stay, less narcotic pain requirement, and
      decreased blood loss when compared with the open procedure. Advantages of the
      robotic platform for dissection and suturing can be useful for complex minimally
      invasive urologic reconstructive procedures.

PMID- 22967285
TI  - Relatively high frequency of non-synonymous GLI2 variants in patients with
      congenital hypopituitarism without holoprosencephaly.
AB  - OBJECTIVE: GLI2 is a downstream transcription factor in Sonic Hedgehog
      signalling, acting early in ventral forebrain and pituitary development.
      Heterozygous nonsense GLI2 mutations have been reported in patients with isolated
      or combined pituitary hormone deficiency (CPHD), with or without
      holoprosencephaly. The aim of this study was to screen for GLI2 mutations in a
      large cohort of patients with congenital GH deficiency. DESIGN AND PATIENTS: The
      GLI2 coding region of 41 patients with severe isolated GH deficiency (IGHD) and
      136 patients with CPHD was amplified by PCR using intronic primers and sequenced.
      The frequency of GLI2 variants was verified in up to 155 Brazilian controls and
      in the 1000 Genomes database. The consequences of allelic variants were analysed
      by the Polyphen, SIFT, Mutationtaster and SNAP prediction sites. RESULTS:
      Eighteen different heterozygous non-synonymous GLI2 variants were identified in
      24 patients. Twenty-three patients had CPHD and one had IGHD. Two patients had
      additional diabetes insipidus, indicating deficiencies of anterior and posterior
      pituitary lobes. The posterior pituitary lobe on MRI was ectopic in 16, not
      visible in 4, normally placed in 2 and imaging was not available in two patients,
      but there were no signs of holoprosencephaly. Sixteen GLI2 variants were
      considered deleterious in at least one of the prediction sites. CONCLUSIONS: A
      relatively high frequency of non-synonymous GLI2 variants was identified in
      patients with congenital GH deficiency without other brain defects, and most of
      these patients presented with CPHD and an ectopic posterior pituitary lobe. In
      vitro functional assays may contribute to ascertain the deleterious consequences
      of these variants.

PMID- 22967286
TI  - Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in
      lithium-responders one month after treatment initiation.
AB  - BACKGROUND: Lithium is considered by many as the gold standard medication in the
      management of bipolar disorder (BD). However, the clinical response to lithium is
      heterogeneous, and the molecular basis for this difference in response is
      unknown. In the present study, we sought to determine how the peripheral blood
      gene expression profiles of patients with bipolar disorder (BD) changed over time
      following intitiation of treatment with lithium, and whether differences in those
      profiles over time were related to the clinical response. METHODS: Illumina
      Sentrix Beadchip (Human-6v2) microarrays containing > 48,000 transcript probes
      were used to measure levels of expression of gene-expression in peripheral blood
      from 20 depressed subjects with BD prior to and every two weeks during 8 weeks of
      open-label treatment with lithium.Changes in gene-expression were compared
      between treatment responders (defined as a decrease in the Hamilton Depression
      Rating Scale of 50% or more) and non-responders. Pathway analysis was conducted
      using GeneGO Metacore software. RESULTS: 127 genes showed a differential response
      in responders vs. non-responders. Pathway analysis showed that regulation of
      apoptosis was the most significantly affected pathway among these genes. Closer
      examination of the time-course of changes among BCL2 related genes showed that in
      lithium-responders, one month after starting treatment with lithium, several anti
      apoptotic genes including Bcl2 and insulin receptor substrate 2 (IRS2) were up
      regulated, while pro-apoptotic genes, including BCL2-antagonist/killer 1 (BAK1)
      and BCL2-associated agonist of cell death (BAD), were down-regulated. In
      contrast, in lithium non-responders, BCL2 and IRS2 were down-regulated, while
      BAK1 and BAD up-regulated at the one-month time-point. CONCLUSIONS: These results
      suggest that differential changes in the balance of pro- and anti- apoptotic gene
      expression following treatment with lithium may explain some of the heterogeneity
      in clinical response in BD patients.

PMID- 22967287
TI  - RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and
      diagnosis.
AB  - The integrin alpha(v)beta(3) plays an important role in angiogenesis. It is
      expressed on tumoral endothelial cells as well as on some tumor cells. RGD
      peptides are well-known to bind preferentially to the alpha(v)beta(3) integrin.
      In this context, targeting tumor cells or tumor vasculature by RGD-based
      strategies is a promising approach for delivering anticancer drugs or contrast
      agents for cancer therapy and diagnosis. RGD-based strategies include antagonist
      drugs (peptidic or peptidomimetic) of the RGD sequence, RGD-conjugates, and the
      grafting of the RGD peptide or peptidomimetic, as targeting ligand, at the
      surface of nanocarriers. Although all strategies are overviewed, this review aims
      to particularly highlight the position of RGD-based nanoparticles in cancer
      therapy and imaging. This review is divided into three parts: the first one
      describes the context of angiogenesis, the role of the integrin alpha(v)beta(3),
      and the binding of the RGD peptide to this integrin; the second one focuses on
      RGD-based strategies in cancer therapy; while the third one focuses on RGD-based
      strategies in cancer diagnosis.

PMID- 22967288
TI  - Comparative analysis of mitochondrial genomes of Rhizophagus irregularis - syn.
      Glomus irregulare - reveals a polymorphism induced by variability generating
      elements.
AB  - Arbuscular mycorrhizal (AM) fungi are involved in one of the most widespread
      plant-fungus interactions. A number of studies on the population dynamics of AM
      fungi have used mitochondrial (mt) DNA sequences, and yet mt AM fungus genomes
      are poorly known. To date, four mt genomes of three species of AM fungi are
      available, among which are two from Rhizophagus irregularis. In order to study
      intra- and interstrain mt genome variability of R. irregularis, we sequenced and
      de novo assembled four additional mt genomes of this species. We used 454
      pyrosequencing and Illumina technologies to directly sequence mt genomes from
      total genomic DNA. The mt genomes are unique within each strain. Interstrain
      divergences in genome size, as a result of highly polymorphic intergenic and
      intronic sequences, were observed. The polymorphism is brought about by three
      types of variability generating element (VGE): homing endonucleases, DNA
      polymerase domain-containing open reading frames and small inverted repeats.
      Based on VGE positioning, mt sequences and nuclear markers, two subclades of R.
      irregularis were characterized. The discovery of VGEs highlights the great
      intraspecific plasticity of the R. irregularis mt genome. VGEs allow the design
      of powerful mt markers for the typing and monitoring of R. irregularis strains in
      genetic and population studies.

PMID- 22967290
TI  - Knowledge gaps in nursing leadership - focusing on health care systems
      organisation.

PMID- 22967289
TI  - Dynamics of catalytic resolution of 2-lithio-N-Boc-piperidine by ligand exchange.
AB  - The dynamics of the racemization and catalytic and stoichiometric dynamic
      resolution of 2-lithio-N-Boc-piperidine (7) have been investigated. The kinetic
      order in tetramethylethylenediamine (TMEDA) for both racemization and resolution
      of the title compound and the kinetic orders in two resolving ligands have been
      determined. The catalytic dynamic resolution is second order in TMEDA and 0.5 and
      0.265 order in chiral ligands 8 and 10, respectively. The X-ray crystal structure
      of ligand 10 shows it to be an octamer. Dynamic NMR studies of the resolution
      process were carried out. Some of the requirements for a successful catalytic
      dynamic resolution by ligand exchange have been identified.

PMID- 22967291
TI  - Adverse risk: a 'dynamic interaction model of patient moving and handling'.
AB  - AIM: The aim of the present study was to examine patient adverse events
      associated with sub-optimal patient moving and handling. BACKGROUND: Few studies
      have examined the patient's perspective on adverse risk during manual handling
      episodes. EVALUATION: A narrative review was undertaken to develop the 'Dynamic
      Interaction Model of Patient Moving and Handling' in an orthopaedic
      rehabilitation setting, using peer-reviewed publications published in English
      between 1992 and 2010. KEY ISSUES: Five predominant themes emerged from the
      narrative review: 'patient's need to know about analgesics prior to
      movement/ambulation'; 'comfort care'; 'mastery of and acceptance of mobility
      aids/equipment'; 'psychological adjustment to fear of falling'; and 'the need for
      movement to prevent tissue pressure damage'. CONCLUSION: Prevalence of
      discomfort, pain, falls, pressure sores together with a specific Direct
      Instrument Nursing Observation (DINO) tool enable back care advisers to measure
      quality of patient manual handling. Evaluation of patients' use of mobility aids
      together with fear of falling may be important in determining patients' recovery
      trajectory. IMPLICATIONS FOR NURSING MANAGEMENT: Clinical governance places a
      responsibility on nurse managers to consider quality of care for their service
      users. 'Dynamic Interaction Model of Nurse-Patient Moving and Handling' provides
      back care advisers, clinical risk managers and occupational health managers with
      an alternative perspective to clinical risk and occupational risk.

PMID- 22967292
TI  - First-line managers' experiences of alternative modes of funding in elderly care
      in Sweden.
AB  - AIM: The aim of this study was to describe first-line managers' experiences of
      alternative modes of funding elderly care in two communities in western Sweden.
      BACKGROUND: A growing elderly population demands alternative modes of funding
      elderly care for better outcomes for patients and better efficiency as it is
      publicly funded through taxation. METHODS: The study comprised a total of eight
      semi-structured interviews with first-line managers working within elderly care.
      The interviews were analysed using manifest qualitative content analysis. Respect
      for the individuals was a main concern in the study. RESULTS: One category,
      quality improvement, and four subcategories freedom of choice, organisational
      structure, quality awareness and market forces effects were identified to
      describe first-line managers' experiences of the operation of elderly care.
      CONCLUSIONS: Quality improvement was an important factor to deal with when
      elderly care was operated in different organisational perspectives, either
      private or public. The first-line manager is a key person for developing a
      learning organisation that encourages both staff, clients and their relatives to
      improve the organisation. Moreover, person-centred care strengthens the client's
      role in the organisation, which is in line with the government's goal for the
      quality improvement of elderly care. However, further research is needed on how
      quality improvement could be developed when different caregivers operate in the
      same market in order to improve care from the elderly perspective. IMPLICATIONS
      FOR NURSING MANAGEMENT: This study highlights alternative modes of funding
      elderly care. The economical perspectives should not dominate without taking care
      of quality improvement when the operation of elderly care is planned and
      implemented. Strategies such as a learning organisational structure built on
      person-centred care could create quality improvement in elderly care.

PMID- 22967293
TI  - The impact of concordant communication in outpatient care planning - nurses'
      perspective.
AB  - AIM: To elucidate registered nurses' experiences of coordinated care planning in
      outpatient care. BACKGROUND: Coordinated care planning has been studied from the
      perspectives of both patients and nurses in inpatient care, but it is deficient
      in outpatient care. METHOD: Qualitative content analysis of interviews with 10
      registered nurses participating in two focus groups. RESULTS: An overall theme
      was identified: creating concordant communication in relation to patient and
      health-care providers. The result is based on four categories and nine
      subcategories. CONCLUSIONS: Nurses need extraordinary communication skills to
      reach concordance in outpatient care planning. In addition to involving and
      supporting the patients and next of kin in the decision-making process, the
      outcome of the nursing process must be understood by colleagues and members of
      other professions and health-care providers (non-nursing). IMPLICATIONS FOR
      NURSING MANAGEMENT: An effective outpatient care-planning process requires that
      care managers understand the impact of communicating, transferring information
      and reaching consensus with other health-care providers, actively supporting
      employees in the outpatient care-planning process and contributing to the
      development of common goals and policy documents across organisational
      boundaries.

PMID- 22967294
TI  - Registered nurses' perceptions of conditions for patient education - focusing on
      organisational, environmental and professional cooperation aspects.
AB  - AIM: To describe nurses' perceptions of conditions for patient education,
      focusing on organisational, environmental and professional cooperation aspects,
      and to determine any differences between primary, municipal and hospital care.
      BACKGROUND: Although patient education is an important part of daily nursing
      practice, the conditions for this work are unclear and require clarification.
      METHOD: A stratified random sample of 701 (83%) nurses working in primary,
      municipal and hospital care completed a 60-item questionnaire. The study is part
      of a larger project. The study items relating to organisation, environment and
      professional cooperation were analysed using descriptive statistics, non
      parametric tests and content analysis. RESULTS: Conditions for patient education
      differ. Nurses in primary care had better conditions and more managerial support,
      for example in the allocation of undisturbed time. CONCLUSIONS: Conditions
      related to organisation, environment and cooperation need to be developed
      further. In this process, managerial support is important, and nurses must ask
      for better conditions in order to carry through patient education. IMPLICATIONS
      FOR NURSING MANAGEMENT: Managerial support for the development of visible patient
      education routines (e.g. allocation of time, place and guidelines) is required.
      One recommendation is to designate a person to oversee educational work.

PMID- 22967296
TI  - The effectiveness of clinical supervision for a group of ward managers based in a
      district general hospital: an evaluative study.
AB  - AIM: To present an evaluative audit assessing the effectiveness of clinical
      supervision for ward managers. BACKGROUND: A year-long project to introduce
      clinical supervision to ward managers was implemented and evaluated. The
      objectives were to evaluate staff perceptions of implementing clinical
      supervision and determine its outcomes. METHOD: An audit evaluation process was
      used. RESULTS: Findings are presented against perceptions, implementation and
      reported outcomes of clinical supervision. Insights were gained into its
      relevance and importance to nurses and the organisation. Findings show that
      clinical supervision was perceived to be effective and helped improve patient
      care, but some feared it becoming a form of managerial control. CONCLUSIONS: Ward
      managers perceived advantages for personal and professional development from
      adopting this process. IMPLICATIONS FOR NURSING MANAGEMENT: There is a need for
      greater understanding of clinical supervision before Trusts implement it. The
      introduction of a resource pack for clinical areas would also be of value.
      Finally, there needs to be a named person who has a special knowledge of clinical
      supervision to act as a champion and change agent in effecting implementation at
      both the executive level and within each clinical area.

PMID- 22967295
TI  - Nursing students' perspectives on the patient and the impact of the nursing
      culture: a meta-synthesis.
AB  - AIM: To explore and interpret how nursing students develop their understanding of
      the patient as a human being. BACKGROUND: Understanding the patient is the main
      characteristic of good, caring performance. In addition, nurse leaders play an
      active role in creating a culture in which nursing students can flourish and
      improve. METHOD: This meta-synthesis was based on Noblit and Hare's meta
      ethnography. RESULTS: The overarching metaphor was interpreted as the nursing
      students' capacity for compassion. Two central metaphors were revealed, based on
      how nursing students developed their understanding of the patient as a human
      being. These central metaphors were labelled 'The open door', comprising seven
      key metaphors and 'The closed door' based on two key metaphors. CONCLUSION:
      During practical training, the students observed both virtuous and unkind nurses.
      Virtue is a skill that can be taught, but not all students were able to learn it.
      Some students acquired the ability to reflect on ethical issues, while others did
      not. Therefore, good role models are of major importance. IMPLICATION FOR NURSING
      MANAGEMENT: The nurse leader should function as a facilitator in the students'
      efforts to gain the capacity to face the suffering patient and to develop an
      understanding of the patient's situation.

PMID- 22967297
TI  - Patient safety culture in home care: experiences of home-care nurses.
AB  - AIM: To explore home-care nurses' experiences of patient safety in their delivery
      of home care to older clients. BACKGROUND: High-risk organisations, such as the
      airline industry and the petroleum industry, have long been preoccupied with
      safety. Only recently has this also become a central theme in health care.
      METHOD: Four focus group interviews with 20 nurses who work in home care. A
      qualitative thematic analysis was performed. RESULTS: One main theme was
      identified: struggling with responsibility in different situations. It comprises
      five subthemes: poor work morale and work ethic; documentation; lack of
      functional leadership; competence; and lack of updated routines and guidelines.
      CONCLUSIONS: Patient safety culture is compromised by a lack of leadership, lack
      of responsibility among leadership, lack of routines, failure to update
      procedures, and a lack of knowledge and education among health-care workers.
      IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers need to be made more aware of
      the dilemmas faced by nurses, how they struggle with their responsibilities, how
      they experience powerlessness in certain situations, and the lack of support they
      receive in decision-making.

PMID- 22967298
TI  - Evaluation of self-management interventions for chronic obstructive pulmonary
      disease.
AB  - AIM: To evaluate the benefits of self-management interventions on the quality of
      life of patients with chronic obstructive pulmonary disease. BACKGROUND: Chronic
      obstructive pulmonary disease is one of the most widespread chronic conditions
      worldwide, and it is predicted to increase over the next decade. Although
      previous review studies have demonstrated the benefits of self-management
      interventions on health-care utilisation, their benefits on quality of life are
      still unclear. METHOD: In this systematic review, we examined four randomised
      controlled trials undertaken between 2000 and 2011 to evaluate the benefits of
      chronic obstructive pulmonary disease self-management interventions on patient
      quality of life. RESULTS: The main theme that emerged was that self-management
      interventions improved patient well-being, with three minor themes: reducing the
      burden on patients, improved patient activity and improved total patient health.
      CONCLUSION: Self-management interventions tend to improve the quality of life of
      patients with chronic obstructive pulmonary disease. Further randomised
      controlled trials are recommended to evaluate self-management interventions in
      chronic obstructive pulmonary disease to confirm these benefits. IMPLICATIONS FOR
      NURSING MANAGEMENT: Nursing management in health services is involved in caring
      for patients with chronic obstructive pulmonary disease and is responsible for
      liaising with other members of the health-care team. We recommend that nursing
      management be engaged in health-care services to develop and implement self
      management interventions for chronic obstructive pulmonary disease patients to
      improve their quality of life.

PMID- 22967299
TI  - Clinical nurses' attitudes towards research, management and organisational
      resources in a university hospital: part 1.
AB  - AIM: The aim of this study was to determine clinical nurses' interest in and
      motivation for research. An additional aim was to identify management and
      organisational resources in order to improve nurses' research capacity in
      practice. BACKGROUND: Clinical nurses find conducting research challenging, which
      accords with observations of the continuing research-practice gap. METHODS: This
      descriptive cross-sectional survey sampled 364 clinical nurses from a university
      hospital on the west coast of Norway. RESULTS: The response rate was 61%. An
      increasingly positive attitude towards research emerged (40%), despite the fact
      that few were engaged in research-based activities. Clinical nurses emphasised
      that lack of designated time (60%), interest (31%) and knowledge (31%)
      constituted important research barriers, as did lack of research supervision and
      support (25%). Research supervision was one of the most significant needs to
      enhance clinical nurses' research skills, management and organisation of research
      activities (30%). CONCLUSION: Conscious efforts strategically built on clinical
      and academic collaborative networks are required to promote and sustain clinical
      nurses' research capacity. IMPLICATION FOR NURSING MANAGEMENT: The findings of
      this survey should be useful in the building of clinical nurses' research
      capacity.

PMID- 22967300
TI  - Clinical nurses' research capacity in a Norwegian university hospital: part 2.
AB  - AIM: To examine clinical nurses' research capacity and investigate related
      factors (i.e. the different phases of the research process). BACKGROUND: Research
      capacity includes research-related activities, being informed and applying
      research. METHODS: A descriptive-correlational design was used and data were
      collected by means of a structured questionnaire (59-items). A total of 364
      registered nurses from a University Hospital participated. The response rate was
      61%. A majority reported that their research capacity was acceptable or weak
      (77.7%), while 7.6% who were involved in research rated it good or excellent;
      19.6% evaluated their level of research competence as fairly good and 4.1% wanted
      to increase their research involvement. RESULTS: The result demonstrated high
      statistical correlation, indicating that nurses are aware of the areas involved
      in research-related activities. Areas of perceived low competence were associated
      with reliability, sensitivity and specificity, control of confounding variables,
      sources of funding and computerised statistical packages. Areas of capacity
      reported were access to literature, data collection, such as interviews and field
      notes, as well as research ethics. CONCLUSION: Enhanced research supervision is
      central for improving registered nurses' research capacity. IMPLICATIONS FOR
      NURSING MANAGEMENT: The findings from this survey should be useful for
      professional development.

PMID- 22967301
TI  - Molecular dynamics simulation of Autotaxin: roles of the nuclease-like domain and
      the glycan modification.
AB  - Autotaxin (ATX) is a secreted lysophospholipase D that produces lysophosphatidic
      acid, a lipid mediator that activates G protein-coupled receptors to evoke
      various cellular responses. The nuclease-like domain of ATX and the Asn524-linked
      glycan are reportedly critical for the catalytic activity. Recently, the crystal
      structures of ATX were determined, but the means by which the nuclease-like
      domain and the N-glycosylation participate in the catalytic activity still remain
      undetermined. To address this question, we conducted molecular dynamics
      simulations of ATX. The simulation trajectories starting from the full-length
      structure and from structures lacking the nuclease-like domain and/or the glycan
      were compared. The results suggested that an allosteric interaction pathway,
      formed by the catalytic domain, including the two insertion regions, the
      essential glycan modification, and the nuclease-like domain, may stabilize the
      proper location of the catalytic threonine residue. The results complement those
      from previous biochemical experiments.

PMID- 22967302
TI  - Occupational competence and its relationship to emotional health in injured
      workers in return to work programs: a Malaysian study.
AB  - Workers with musculoskeletal disorders undertaking Malaysia's return to work
      (RTW) programmes may experience challenges in occupational competence (OC) and
      negative emotional states (NES). This study aimed to measure and examines the OC
      and NES of the workers by comparing specific comparison groups and groups of
      different phases. A total of 76 participants were recruited from a national RTW
      programme and categorized into three groups based on different RTW phases: off
      work (n = 22), re-entry (n = 31), and maintenance (n = 23). Self-report
      questionnaires consisted of the Occupational Self Assessment version 2.2 and the
      Depression, Anxiety and Stress Scale-21. Results showed that injured workers
      exhibited significantly lower OC in comparison with an international group with
      various disabilities. In contrast, there was significantly higher NES when
      compared with Malaysia's general population. Significant differences in OC and
      NES were also found between workers in the three RTW phases. In particular, OC
      and NES in the off-work and re-entry phases were significantly lower (OC) and
      higher (NES) than in the maintenance phase. Furthermore, there was a moderate,
      negative correlation between OC and NES in the off-work and re-entry phase
      groups. This indicated that low levels of perceived OC were associated with
      higher levels of NES.

PMID- 22967303
TI  - Taste ability in hospitalised older people compared with healthy, age-matched
      controls.
AB  - OBJECTIVE: To investigate whether taste ability is reduced in acutely
      hospitalised older people compared with healthy, age-matched, non- hospitalised
      controls. BACKGROUND: Proper gustatory function in older people is important for
      quality of life and enjoyment of food. Impaired taste may contribute to weight
      loss in elderly. MATERIAL AND METHODS: Cross- sectional study. The participants
      comprised two groups with age >= 70 years. Older people hospitalised for acute
      disease, home-living prior to hospital admission and with adequate cognitive
      function (n = 174 with mean age = 84 years). The controls (n = 63, mean age 82
      years) were home-living, and healthy by their own judgement. Whole mouth
      gustatory function was assessed with taste strips impregnated with sweet, sour,
      bitter and salty taste solutions in four different concentrations each. Correct
      identifications were summarized, and maximum total score was 16. RESULTS: Total
      taste score was reduced in the hospitalised group compared with the control group
      (p = 0.035). The difference was mainly due to reduced ability to detect sour and
      bitter taste qualities (p < 0.001 and p = 0.003). CONCLUSION: Acutely
      hospitalised older people had significantly reduced taste ability compared with
      non-hospitalised controls. Sour and bitter taste qualities were mostly affected.
      Hospital staff should pay attention to these findings when preparing food for
      hospitalised older people.

PMID- 22967305
TI  - Low testosterone levels induce apoptosis via active 3-caspase dependent signaling
      in the bladder wall of male rats.
AB  - OBJECTIVE: The bladder can be considered a target organ for testosterone action,
      and low testosterone levels possibly cause damage to bladder cells. We set out to
      study whether hypoandrogenism influences bladder wall cell damage in castrated
      and senile male rats. METHODS: Thirty male Wistar rats were divided into three
      groups of 10 animals each: group I (3 months old), sham animals; group II (27
      months old), senile animals; group III (3 months old), subjected to bilateral
      orchiectomy, and sacrificed 8 weeks after the procedure. Bladders were excised,
      weighed and sent for analysis. Stereological assays on collagen fibers and
      immunohistochemical analysis with active 3-caspase were performed on bladder
      cells. RESULTS: Bladder weights were greater in the senile group than in the
      others. Stereological collagen fiber analysis demonstrated higher density in
      group III than in groups I and II (p < 0.05). The absolute density was 4.15 mm(3)
      in group I, 22.3 mm(3) in group II and 19.3 mm(3) in group III. Semiquantitative
      active 3-caspase analysis showed greater percentages in the senile group II than
      in groups I and III. CONCLUSIONS: We can state that low plasma testosterone
      levels are related to higher collagen fiber density and active 3-caspase
      percentages in the bladder walls of orchiectomized and senile rats, respectively.

PMID- 22967304
TI  - Lactobacillus plantarum possesses the capability for wall teichoic acid backbone
      alditol switching.
AB  - BACKGROUND: Specific strains of Lactobacillus plantarum are marketed as health
      promoting probiotics. The role and interplay of cell-wall compounds like wall-
      and lipo-teichoic acids (WTA and LTA) in bacterial physiology and probiotic-host
      interactions remain obscure. L. plantarum WCFS1 harbors the genetic potential to
      switch WTA backbone alditol, providing an opportunity to study the impact of WTA
      backbone modifications in an isogenic background. RESULTS: Through genome mining
      and mutagenesis we constructed derivatives that synthesize alternative WTA
      variants. The mutants were shown to completely lack WTA, or produce WTA and LTA
      that lack D-Ala substitution, or ribitol-backbone WTA instead of the wild-type
      glycerol-containing backbone. DNA micro-array experiments established that the
      tarIJKL gene cluster is required for the biosynthesis of this alternative WTA
      backbone, and suggest ribose and arabinose are precursors thereof. Increased
      tarIJKL expression was not observed in any of our previously performed DNA
      microarray experiments, nor in qRT-PCR analyses of L. plantarum grown on various
      carbon sources, leaving the natural conditions leading to WTA backbone alditol
      switching, if any, to be identified. Human embryonic kidney NF-kappaB reporter
      cells expressing Toll like receptor (TLR)-2/6 were exposed to purified WTAs
      and/or the TA mutants, indicating that WTA is not directly involved in TLR-2/6
      signaling, but attenuates this signaling in a backbone independent manner, likely
      by affecting the release and exposure of immunomodulatory compounds such as LTA.
      Moreover, human dendritic cells did not secrete any cytokines when purified WTAs
      were applied, whereas they secreted drastically decreased levels of the pro
      inflammatory cytokines IL-12p70 and TNF-alpha after stimulation with the WTA
      mutants as compared to the wild-type. CONCLUSIONS: The study presented here
      correlates structural differences in WTA to their functional characteristics,
      thereby providing important information aiding to improve our understanding of
      molecular host-microbe interactions and probiotic functionality.

PMID- 22967306
TI  - A new gorgostane derivative from the Egyptian Red Sea soft coral Heteroxenia
      ghardaqensis.
AB  - Chemical investigation of the chloroform extract of the Egyptian Red Sea soft
      coral, Heteroxenia ghardaqensis (Family Xeniidae), led to the isolation of three
      gorgostane derivatives, namely gorgosten-5(E)-3beta-ol (1), gorgostan
      3beta,5alpha,6beta, 11alpha-tetraol (sarcoaldosterol A) (2) and gorgostan
      3beta,5alpha,6beta-triol-11alpha-acetate (3). To our knowledge, sterol 3 is
      reported in this article for the first time. The structure elucidation of these
      compounds was deduced by 1-D and 2-D NMR as well as ESIMS. Sterol 1 showed
      moderate activity as growth inhibitor of human colon tumour cell lines. 

PMID- 22967308
TI  - Successful treatment of methemoglobinemia in an elderly couple with severe
      cyanosis: two case reports.
AB  - INTRODUCTION: Methemoglobinemia should be considered in all cyanotic patients who
      remain unresponsive to oxygen therapy. Rapid diagnosis is very important in
      emergency cases. Here, we present the cases of two patients, a married couple,
      admitted to our hospital with methemoglobinemia after exposure to sodium nitrite.
      CASE PRESENTATION: Two patients, a married couple, presented with
      methemoglobinemia. The 72-year-old Taiwanese man and 68-year-old Taiwanese woman
      were referred to our hospital with dizziness and tachypnea. On examination, their
      mucous membranes were cyanotic, and their blood samples showed the classic
      'chocolate brown' appearance. The man also reported having experienced twitching
      of his right arm for a few minutes before arrival at the hospital. The symptoms
      of both patients failed to improve in response to supplemental oxygen delivered
      via oxygen masks, although the arterial blood gas data of these patients were
      normal and their pulse oximetry showed oxyhemoglobin levels of approximately 85%.
      A carbon monoxide-oximeter showed that the man's methemoglobin concentration was
      48.3%, and the woman's was 36.4%. Methylene blue (100mg) was administered
      intravenously to both patients, and their symptoms improved dramatically. They
      were admitted to the intensive care unit and discharged three days later, without
      neurological sequelae. CONCLUSION: Severe methemoglobinemia is a life-threatening
      condition and, if untreated, may result in death. Early diagnosis and appropriate
      antidotal treatment are crucial in treating this emergency situation.

PMID- 22967309
TI  - Molecular characterization of Echinococcus granulosus in south-eastern Romania:
      evidence of G1-G3 and G6-G10 complexes in humans.
AB  - Clin Microbiol Infect ABSTRACT: Echinococcus granulosus is the aetiological agent
      of cystic echinococcosis (CE), which is a public health problem in many eastern
      European countries, particularly in Romania, where the infection causes a high
      number of human and animal cases. To shed light on the transmission patterns of
      the parasite, we performed a genotyping analysis on 60 cyst samples obtained from
      patients who live in south-eastern Romania and who underwent surgery for liver or
      lung CE. DNA was extracted from the endocysts or the cyst fluids, and fragments
      of cytochrome c oxidase subunit 1 and NADH dehydrogenase subunit 1 mitochondrial
      genes (cox1 and nd1, respectively) were amplified by PCR and sequenced. We found
      that most of the samples analysed (59/60) belonged to the G1-G3 complex (E.
      granulosus sensu stricto), which contains the most widespread and infective
      strains of the parasite. We also identified the first human patient infected by a
      non-G1-G3 genotype of E. granulosus in this country. As the DNA sequence of this
      cyst sample showed maximum homology with the G6-G10 complex (Echinococcus
      canadensis), this is, in all likelihood, a G7 genotype, which is often found in
      pigs and dogs in most countries of eastern and south-eastern Europe.

PMID- 22967310
TI  - Denosumab: mechanism of action and clinical outcomes.
AB  - AIMS: To describe the mechanisms of action of denosumab, a novel antiresorptive
      agent, contrasting it with other antiresorptive and anabolic osteoporosis
      treatments. METHODS: Published papers related to the mechanism of action of
      approved osteoporosis treatments were sought through MEDLINE searches. FINDINGS:
      Osteoporotic fractures carry a substantial burden of morbidity and mortality, but
      pharmacotherapy can prevent such fractures in high-risk individuals.
      Antiresorptive drugs (e.g. bisphosphonates, oestrogen, denosumab) reduce bone
      turnover by distinct mechanisms. Denosumab, a recently approved therapy, is a
      fully human monoclonal antibody that binds the cytokine RANKL (receptor activator
      of NFkappaB ligand), an essential factor initiating bone turnover. RANKL
      inhibition blocks osteoclast maturation, function and survival, thus reducing
      bone resorption. In contrast, bisphosphonates bind bone mineral, where they are
      absorbed by mature osteoclasts, inducing osteoclast apoptosis and suppressing
      resorption. These differences in mechanism influence both the onset and
      reversibility of treatment. DISCUSSION: Effective pharmacotherapy is necessary
      for patients at high risk of fracture. Among the treatment options for
      postmenopausal osteoporosis, there are significant differences in mechanism and
      dosing. Denosumab acts by a novel mechanism and is administered twice yearly by
      subcutaneous injection. Identified by Osteoporosis Canada Clinical Practice
      Guidelines as a first-line agent for treatment of postmenopausal osteoporosis,
      denosumab represents an important addition to our treatment options.

PMID- 22967311
TI  - Viral metagenomic analysis of bushpigs (Potamochoerus larvatus) in Uganda
      identifies novel variants of Porcine parvovirus 4 and Torque teno sus virus 1 and
      2.
AB  - BACKGROUND: As a result of rapidly growing human populations, intensification of
      livestock production and increasing exploitation of wildlife habitats for animal
      agriculture, the interface between wildlife, livestock and humans is expanding,
      with potential impacts on both domestic animal and human health. Wild animals
      serve as reservoirs for many viruses, which may occasionally result in novel
      infections of domestic animals and/or the human population. Given this
      background, we used metagenomics to investigate the presence of viral pathogens
      in sera collected from bushpigs (Potamochoerus larvatus), a nocturnal species of
      wild Suid known to move between national parks and farmland, in Uganda. RESULTS:
      Application of 454 pyrosequencing demonstrated the presence of Torque teno sus
      virus (TTSuV), porcine parvovirus 4 (PPV4), porcine endogenous retrovirus (PERV),
      a GB Hepatitis C-like virus, and a Sclerotinia hypovirulence-associated-like
      virus in sera from the bushpigs. PCR assays for each specific virus combined with
      Sanger sequencing revealed two TTSuV-1 variants, one TTSuV-2 variant as well as
      PPV4 in the serum samples and thereby confirming the findings from the 454
      sequencing. CONCLUSIONS: Using a viral metagenomic approach we have made an
      initial analysis of viruses present in bushpig sera and demonstrated for the
      first time the presence of PPV4 in a wild African Suid. In addition we identified
      novel variants of TTSuV-1 and 2 in bushpigs.

PMID- 22967312
TI  - MYB103 is required for FERULATE-5-HYDROXYLASE expression and syringyl lignin
      biosynthesis in Arabidopsis stems.
AB  - The transcription factor MYB103 was previously identified as a member of the
      transcriptional network regulating secondary wall biosynthesis in xylem tissues
      of Arabidopsis, and was proposed to act on cellulose biosynthesis. It is a direct
      transcriptional target of the transcription factor SECONDARY WALL ASSOCIATED NAC
      DOMAIN PROTEIN 1 (SND1), and 35S-driven dominant repression or over-expression of
      MYB103 modifies secondary wall thickness. We identified two myb103 T-DNA
      insertion mutants and chemically characterized their lignocellulose by
      pyrolysis/GC/MS, 2D NMR, FT-IR microspectroscopy and wet chemistry. The mutants
      developed normally but exhibited a 70-75% decrease in syringyl (S) lignin. The
      level of guaiacyl (G) lignin was co-ordinately increased, so that total Klason
      lignin was not affected. The transcript abundance of FERULATE-5-HYDROXYLASE
      (F5H), the key gene in biosynthesis of S lignin, was strongly decreased in the
      myb103 mutants, and the metabolomes of the myb103 mutant and an F5H null mutant
      were very similar. Other than modification of the lignin S to G ratio, there were
      only very minor changes in the composition of secondary cell-wall polymers in the
      inflorescence stem. In conclusion, we demonstrate that F5H expression and hence
      biosynthesis of S lignin are dependent on MYB103. 

PMID- 22967314
TI  - Molecular structure and metabolic characteristics of the proteins and energy in
      triticale grains and dried distillers grains with solubles for dairy cattle.
AB  - To our knowledge, there is no research on the molecular structure of triticale
      grain in comparison with other types of cereal grains and metabolic
      characteristics of the protein and energy in this grain and its coproducts,
      called dried distillers grains with solubles (DDGS), for dairy cattle. The
      objective of this study was to identify differences in molecular structures of
      proteins among grains and their DDGS using a molecular spectroscopy technique,
      namely, DRIFT, and to determine the nutrient profile and supply to dairy cattle.
      The protein molecular structure studies showed a difference (P < 0.01) in the
      amide I to amide II ratio and the alpha-helix to beta-sheet ratio between grains
      and their DDGS. The energy content was similar for triticale grain and DDGS.
      There were differences in the protein and carbohydrate subfractions (P < 0.05)
      and the ruminal degradability of DM, CP, and NDF (P < 0.01) between triticale
      grain and DDGS. Triticale grain and DDGS had similar intestinal digestibility of
      rumen undegraded CP. However, triticale DDGS had higher (P < 0.01) predicted
      total metabolizable protein and degraded protein balance than triticale,
      indicating that triticale DDGS is a superior protein source for dairy cattle as
      compared with triticale grain. Bioethanol processing induced changes in the
      protein molecular structure. 

PMID- 22967313
TI  - Microbial community structure and dynamics in anaerobic fluidized-bed and
      granular sludge-bed reactors: influence of operational temperature and reactor
      configuration.
AB  - Methanogenic community structure and dynamics were investigated in two different,
      replicated anaerobic wastewater treatment reactor configurations [inverted
      fluidized bed (IFB) and expanded granular sludge bed (EGSB)] treating synthetic
      dairy wastewater, during operating temperature transitions from 37 degrees C to
      25 degrees C, and from 25 degrees C to 15 degrees C, over a 430-day trial. Non
      metric multidimensional scaling (NMS) and moving-window analyses, based on
      quantitative real-time PCR data, along with denaturing gradient gel
      electrophoresis (DGGE) profiling, demonstrated that the methanogenic communities
      developed in a different manner in these reactor configurations. A comparable
      level of performance was recorded for both systems at 37 degrees C and 25 degrees
      C, but a more dynamic and diverse microbial community in the IFB reactors
      supported better stability and adaptative capacity towards low temperature
      operation. The emergence and maintenance of particular bacterial genotypes
      (phylum Firmicutes and Bacteroidetes) was associated with efficient protein
      hydrolysis in the IFB, while protein hydrolysis was inefficient in the EGSB. A
      significant community shift from a Methanobacteriales and Methanosaetaceae
      towards a Methanomicrobiales-predominated community was demonstrated during
      operation at 15 degrees C in both reactor configurations.

PMID- 22967315
TI  - In silico-aided design of a glycan ligand of sialoadhesin for in vivo targeting
      of macrophages.
AB  - Cell-specific delivery of therapeutic agents using ligand targeting is gaining
      interest because of its potential for increased efficacy and reduced side
      effects. The challenge is to develop a suitable ligand for a cell-surface
      receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn,
      Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec)
      expressed on subsets of resident and inflammatory macrophages, is an attractive
      target for the development of a ligand-targeted delivery system. Here we report
      the development of a high-affinity and selective ligand for Sn that is an
      analogue of the natural ligand and is capable of targeting liposomal
      nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a
      library of ~8400 carboxylic acids was the key to identifying novel 9-N-acyl
      substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead
      compounds. A small panel of targets were selected from the screen and synthesized
      to evaluate their affinities and selectivities. The most potent of these Sn
      ligands, 9-N-(4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Acalpha2-3Galbeta1
      4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal
      nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac
      liposomes were found to target liposomes selectively to cells expressing either
      murine or human Sn in vitro, and when administered to mice, they exhibited in
      vivo targeting to Sn-positive macrophages.

PMID- 22967316
TI  - Characterization of insulin resistance in young adult survivors of childhood
      acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
AB  - INTRODUCTION: An increased prevalence of metabolic disorders and cardiovascular
      (CV) disease has been reported in childhood acute lymphoblastic leukaemia
      (ALL)/non-Hodgkin lymphoma (NHL) cancer survivors. OBJECTIVE: To characterize the
      determinants of insulin resistance (IR) observed in this population, according to
      the treatment received. METHODS: Ninety one patients (45 men, mean age: 24 +/- 5
      years; mean follow-up: 15 +/- 5 years) previously treated for a childhood ALL (n
      = 76) or NHL (n = 15) were grouped according to their previous treatment:
      chemotherapy only (Group I; n = 43), chemotherapy + cranial irradiation (CI)
      (Group II; n = 32) and chemotherapy + bone marrow transplant (BMT)/total body
      irradiation (TBI) (Group III, n = 16). RESULTS: A high prevalence of IR (HOMA-S <
      60%) was observed in the BMT/TBI group (88%) compared to groups I (9%) and II
      (16%). The IR patients from groups [I+II] (12% of these groups) showed higher
      BMI, fat mass (FM) and visceral fat when compared with the non-IR patients. In
      contrast, the IR patients from group III had mean BMI and total FM similar to
      those of non-IR patients but showed a reduction of lean body mass and an increase
      in the relative proportion of trunk FM similar to the IR patients from groups [I
      + II]. This was associated with an altered lipid profile, high TNF-alpha and IL-6
      levels, and reduced adiponectin levels compared to IR patients from group [I +
      II] and non-IR patients. CONCLUSION: Childhood ALL/NHL survivors treated by
      BMT/TBI frequently develop severe insulin resistance associated with peripheral
      to-central fat redistribution, rather than increased total FM, and low
      adiponectin levels which may contribute to their increased CV risk.

PMID- 22967317
TI  - Novel screening assay for in vivo selection of Klebsiella pneumoniae genes
      promoting gastrointestinal colonisation.
AB  - BACKGROUND: Klebsiella pneumoniae is an important opportunistic pathogen causing
      pneumonia, sepsis and urinary tract infections. Colonisation of the
      gastrointestinal (GI) tract is a key step in the development of infections; yet
      the specific factors important for K. pneumoniae to colonize and reside in the GI
      tract of the host are largely unknown. To identify K. pneumoniae genes promoting
      GI colonisation, a novel genomic-library-based approach was employed. RESULTS:
      Screening of a K. pneumoniae C3091 genomic library, expressed in E. coli strain
      EPI100, in a mouse model of GI colonisation led to the positive selection of five
      clones containing genes promoting persistent colonisation of the mouse GI tract.
      These included genes encoding the global response regulator ArcA; GalET of the
      galactose operon; and a cluster of two putative membrane-associated proteins of
      unknown function. Both ArcA and GalET are known to be involved in metabolic
      pathways in Klebsiella but may have additional biological actions beneficial to
      the pathogen. In support of this, GalET was found to confer decreased bile salt
      sensitivity to EPI100. CONCLUSIONS: The present work establishes the use of
      genomic-library-based in vivo screening assays as a valuable tool for
      identification and characterization of virulence factors in K. pneumoniae and
      other bacterial pathogens.

PMID- 22967318
TI  - Multiple metal binding to the 9-methyladenine model nucleobase involving N1, N6,
      and N7: discrete di- and trinuclear species with different combinations of
      monofunctional Pd(II) and Pt(II) entities.
AB  - Several di- and trinuclear metal complexes consisting of the model nucleobase 9
      methyladenine (9-MeA) or its mono-deprotonated form (9-MeA(-)) and monofunctional
      (dien)Pd(II), (dien)Pt(II), (NH(3))(3)Pt(II), or (trpy)Pd(II) in different
      combinations have been prepared and/or studied in solution by NMR spectroscopy:
      [{Pd(dien)}(3)(9-MeA(-)-N1,N6,N7)]Cl(3.5)(PF(6))(1.5).3H(2)O (1), [(dien)Pd(N1-9
      MeA-N7)Pt(NH(3))(3)](ClO(4))(4).9.33H(2)O (2), [(dien)Pt(N1-9-MeA
      N7)Pt(NH(3))(3)](ClO(4))(4).H(2)O (3), and [{(trpy)Pd}(2)(N1,N6-9-MeA(-)
      N7)Pt(NH(3))(3)](ClO(4))(5).3H(2)O (4). A migration product of 3, [(dien)Pt(N6-9
      MeA(-)-N7)Pt(NH(3))(3)](3+) (3a), has been identified in solution. Unlike Pt
      adenine bonds, Pd-adenine bonds are substantially labile, and consequently all Pd
      containing complexes discussed here (1, 2, 4) exist in aqueous solution in
      equilibria of slowly interconverting species, which give rise to individual
      resonances in the (1)H NMR spectra. For example, 1 exists in an equilibrium of
      five adenine-containing species when dissolved in D(2)O, 2 undergoes dissociation
      to [Pt(NH(3))(3)(9-MeA-N7)](2+) or forms the migration product [(dien)Pd(N6-9
      MeA(-)-N7)Pt(NH(3))(3)](3+) (2a), depending on pD, and 4 loses both (trpy)Pd(II)
      entities as the pD is increased. In no case is Pd binding to N3 of the adenine
      ring observed. A comparison of the solid-state structures of the two trinuclear
      complexes 1 and 4 reveals distinct differences between the Pd atoms bonded to N1
      and N6 in that these are substantially out of the nucleobase plane in 1, by ca.
      0.6 A and -1.0 A, respectively, whereas they are coplanar with the 9-MeA(-) plane
      in 4. These out-of-plane movements of the two (dien)Pd(II) units in 1 are not
      accompanied by changes in hybridization states of the N1 and N6 atoms.

PMID- 22967319
TI  - Hierarchical super-structure identified by polarized light microscopy, electron
      microscopy and nanoindentation: Implications for the limits of biological control
      over the growth mode of abalone sea shells.
AB  - BACKGROUND: Mollusc shells are commonly investigated using high-resolution
      imaging techniques based on  cryo-fixation. Less detailed information is
      available regarding the light-optical properties. Sea shells of Haliotis
      pulcherina were embedded for polishing in defined orientations in order to
      investigate the interface between prismatic calcite and nacreous aragonite by
      standard materialographic methods. A polished thin section of the interface was
      prepared with a defined thickness of 60 MUm for quantitative birefringence
      analysis using polarized light and LC-PolScope microscopy. Scanning electron
      microscopy images were obtained for comparison. In order to study structural
      mechanical relationships, nanoindentation experiments were performed. RESULTS:
      Incident light microscopy revealed a super-structure in semi-transparent regions
      of the polished cross-section under a defined angle. This super-structure is not
      visible in transmitted birefringence analysis due to the blurred polarization of
      small nacre platelets and numerous organic interfaces. The relative orientation
      and homogeneity of calcite prisms was directly identified, some of them with
      their optical axes exactly normal to the imaging plane. Co-oriented "prism
      colonies" were identified by polarized light analyses. The nacreous super
      structure was also visualized by secondary electron imaging under defined angles.
      The domains of the super-structure were interpreted to consist of
      crystallographically aligned platelet stacks. Nanoindentation experiments showed
      that mechanical properties changed with the same periodicity as the domain size.
      CONCLUSIONS: In this study, we have demonstrated that insights into the growth
      mechanisms of nacre can be obtained by conventional light-optical methods. For
      example, we observed super-structures formed by co-oriented nacre platelets as
      previously identified using X-ray Photo-electron Emission Microscopy (X-PEEM)
      [Gilbert et al., Journal of the American Chemical Society 2008, 130:17519-17527].
      Polarized optical microscopy revealed unprecedented super-structures in the
      calcitic shell part. This bears, in principle, the potential for in vivo studies,
      which might be useful for investigating the growth modes of nacre and other shell
      types.

PMID- 22967322
TI  - Role of "non-cardiac" voltage-gated sodium channels in cardiac cells.

PMID- 22967323
TI  - [Emphasize the transformation of epidemiological research findings].

PMID- 22967324
TI  - [A case-control study on risk factors that associated with severe hand-foot-mouth
      disease in Shanghai].
AB  - OBJECTIVE: To explore the factors associated with severe hand-food-mouth disease
      (HFMD) case in Shanghai. METHODS: A total of 105 severe HFMD cases diagnosed from
      May to July, 2011 in Shanghai were enrolled as case group while another 210 mild
      HFMD cases were randomly selected as control group in the same period. All
      subject's parents or babysitters were asked to fill in the questionnaire in which
      including demography, ways of babysitting, behavior and the like. All HFMD cases
      were diagnosed by both clinical symptom and nuclear acid testing. Data was
      processed by EpiData (V3.0) and analyzed by SPSS (V17.0). RESULTS: Factors as
      age, gender, Diaspora pattern, migrant, size of house, numbers of family member,
      numbers of children, frequency of seeing doctor, dishware that sharing with
      babysitter, food chewed by babysitter, dirty hand, EV71 virus type and diagnosis
      on HFMD in the fist visit to hospital were found associated with severe HFMD by
      univariate analysis. RESULTS: through multivariate logistic regression showed
      that factors including: being the only male kid, more than 3 children in the
      family, dirty hands, unable to be diagnosed as HFMD in the first visit to the
      hospital, visiting doctor during the past 6 months for 2 and 3 times etc. could
      be kept in the model with statistical threshold of 0.05. Adjusted ORs and
      confidence intervals of them were 2.431 (1.317 - 4.487), 2.661 (1.332 - 5.315),
      3.403 (1.871 - 6.191), 6.607 (3.011 - 14.500), 2.431 (1.111 - 5.321), 2.628
      (1.137 - 6.071) respectively. Being Infected by EV71 was also found a very
      important risk factor compared with CoxA16 or other enteroviruses, and its
      adjusted OR was 5.614 (2.409 - 13.082). CONCLUSION: It was necessary to implement
      molecular diagnosis for identifying the virus type of HFMD, together with
      improvement on the capacity of clinical diagnosis in order to diagnose the HFMD
      cases earlier. More attention should be paid to these HFMD cases with EV71
      infection as well as prompting frequent visits to hospitals on those families
      with more children.

PMID- 22967325
TI  - [Risk related to the transmission of H5N1 subtype avian influenza virus in the
      environment of poultry markets in Changsha, China].
AB  - OBJECTIVE: To investigate the risk of H5N1 subtype avian influenza virus (AIV)
      transmission in the poultry market environment in Changsha city. H5N1 antibody
      levels among the groups related occupational exposure and AIV nucleic acid in the
      environment of poultry markets were detected. The characteristics of
      haemagglutinin (HA) genes of H5N1 AIV in the environment were analyzed. METHODS:
      One district and one county from Changsha city were selected randomly and two
      poultry markets at inner city or township levels were selected in the same
      district or county respectively. H5N1 antibody of the occupational exposure
      groups in the poultry market was tested and AIV nucleic acid in the poultry
      market environment monitored. One hundred and two blood samples of the
      occupational exposure groups were tested for H5N1 antibody with single
      radioimmunoassay diffusion hemolysis (SRH) while 160 environment samples (from
      sewage, birds stools, feathers and smearing samples of poultry cages) in the
      poultry market were also detected for AIV nucleic acid with real-time PCR method.
      Four sewage samples of H5N1 subtype AIV were collected from poultry markets in
      Changsha, and the HA genes of H5N1 subtype AIV amplified by RT-PCR and then
      sequenced with TA cloning. Amino acid sequence alignment and phylogenetic tree
      analysis were conducted by Lasergene and Mega 5.0 software. RESULTS: The results
      through H5N1 antibody monitoring program showed that H5N1 antibody positive rates
      from workers were 25.5% (26/102), 50.0% (9/18) and 25.4% (17/67) respectively in
      the poultry markets of township and inner cities. H5N1 antibody positive rate in
      the township poultry markets was higher than in the inner cities poultry markets.
      RESULTS: from the surveillance on AIV nucleic acid showed that the overall H5
      subtype positive rate in Changsha poultry markets was 31.3% (50/160), and the
      positive rate of townships poultry markets was 37.3% (31/83), which were both
      higher than those from the inner cities poultry markets (24.7%, 19/77). H5
      subtype AIV positive rate was different in the tested specimens, with ranking of
      positive rates were sewage (50.0%, 24/48), feathers (44.5%, 4/9), birds stools
      (29.8%, 14/47) and smearing samples of poultry cages (14.3%, 8/56), with
      statistically significant differences (P < 0.01). Four H5N1 HA genes TA cloning
      were successfully constructed and identified as Eurasian branch, similar to
      viruses isolated in mainland China and Hong Kong in the same group, according to
      genetic analysis. Sequence data of the four HA genes showed the same feature of
      high pathogenicity, compared to the H5N1 AIV from mainland China of human origin.
      The receptor specificities were still with avian influenza origin (QSG) and the
      connecting peptide between HA1 and HA2 possessing the polybasic motif (RERRRKK or
      RERRGKK). CONCLUSION: One of the reasons for H5N1 antibody positive rate of 25.5%
      among poultry markets workers was that there were large numbers of H5N1 subtype
      AIV detected in the environment of poultry markets and HA genes of H5N1 subtype
      AIV in the poultry markets environment carried molecular characteristics of
      highly pathogenic which could increase the risk for H5N1 subtype AIV transmission
      in the environment of poultry markets.

PMID- 22967326
TI  - [Correlation between obesity index and blood pressure in Kazak childhood from
      Yili, Xinjiang].
AB  - OBJECTIVE: To investigate the correlations between obesity index such as waist
      circumference, hip circumference, skin-fold thickness, body mass index, waist to
      hip ratio, waist to height ratio etc, and blood pressure among Kazak children
      living in Yili of Xinjiang. METHODS: In May-June 2009, 2438 Kazak children aged 7
      to 14 at primary schools in Yili of Xinjiang, were investigated. Waist
      circumference, hip circumference, skin-fold thickness, systolic and diastolic
      blood pressure were measured to calculate the body mass index, waist to hip ratio
      and waist to height ratio. Analysis on the differences in age and gender, blood
      pressure (BP) between hypertensive or normal BP group under the standard set for
      children. SPSS 17.0 software was used for statistical analysis on its
      correlation. RESULTS: The total prevalence of hypertension was 5.7% in Kazak
      ethnic school-age children in Yili, with 4.4% in the boys and 7.0% in girls. Data
      from waist circumference, hip circumference, waist-height-ratio, waist-hip ratio,
      systolic and diastolic blood pressure showed gender and age differences (P =
      0.000). Average systolic blood pressure was correlated to waist circumference,
      hip circumference, skin-fold thickness, body mass index and waist to hip ratio (P
      = 0.000), with hip circumference the most (man: r = 0.618, female: r = 0.655).
      The average diastolic blood pressure was correlated to waist circumference, hip
      circumference, skin-fold thickness, body mass index and waist to hip ratio (P =
      0.000), with hip having the strongest relation (r = 0.489 for male and r = 0.548
      for females). Significant differences were seen between Hypertension group and
      normal blood pressure group on waist circumference, hip circumference, skin-fold
      thickness, body mass index and waist-hip ratio (P < 0.05). CONCLUSION: In Yili of
      Xinjiang, the prevalence of hypertension was at the low level in Kazak ethnic
      school-aged children when comparing to data from national and foreign standards.
      Indicators related to obesity as waist circumference, hip circumference, body
      mass index and waist to hip ratio were positively correlated with blood pressure,
      with hip in particular.

PMID- 22967327
TI  - [Psychological factors of adopting and maintaining physical activity for
      individuals with hypertension in a community].
AB  - OBJECTIVE: To examine the impact of psychosocial factors on physical activity, so
      as to provide guidance for the development of an effective physical activity
      intervention program for individuals with hypertension. METHODS: This study used
      a baseline data from an intervention study on regular physical activity among
      hypertensive individuals. A multi-stage, stratified random sampling was utilized
      and finally 12 communities from 6 urban districts were chosen. Questionnaires
      were administrated through face-to-face interviews. A total of 586 participants
      were recruited and finally 559 completed the interviews with the response rate as
      95.4%. Descriptive statistics and Cronbach's alpha coefficients were used to test
      the reliability. General Linear Model analysis was used to analyze the
      relationship between stages of physical activity and psychological factors.
      RESULTS: Psychosocial measures on physical activity demonstrated good reliability
      with Cronbach alpha coefficient from 0.7 to 0.9. The scores for each
      psychological measures increased by increasing the scores of stages of physical
      activity. General Linear Model analysis revealed self-efficacy (beta = 0.379)
      while enjoyment of physical activity (beta = 0.234) was significantly correlated
      with physical activity (P < 0.05). The behavioral processes and family support
      marginally increased the physically activity (beta = 0.069 for behavioral
      processes and beta = 0.163 for family support, P < 0.10). CONCLUSION: Our
      findings were informative for the development of community-based intervention
      programs on physical activity among hypertensive individuals. It indicated that
      physical activity intervention programs should be psychosocial theory-based,
      especially increasing their self-confidence and enjoyment, as well as with family
      support, in order to adopt and maintain the physical activities.

PMID- 22967328
TI  - [Results of a screening program on high incidence area of esophageal cancer in
      Yanting Sichuan from 2006 to 2011].
AB  - OBJECTIVE: To study the prevalence of esophageal cancer and various lesions of
      esophagus in high risk areas through a screening program for early diagnosis and
      treatment. METHODS: Random cluster sampling method was used to select some
      portions of a natural village as screening object in the high risk areas of
      esophageal cancer, from 2006 to 2011. Endoscope iodine staining and index biopsy
      screening methods were used on people with high risk and followed by pathological
      exams for confirmation. RESULTS: The detection rates regarding mild esophageal
      hyperplasia, moderate and severe esophageal hyperplasia were 5.33% (803/15 065),
      1.28% (193/15 065), 0.68% (102/15 065) respectively while the detection rates on
      carcinoma in situ, intramucosal carcinoma and invasive cancer were 0.15% (22/15
      065), 0.06% (9/15 065), 0.29% (43/15 065) respectively. The detection rate in
      male esophageal hyperplasia was higher than in female. People younger than 65
      years old, the detection rates on mild, moderate or severe esophageal hyperplasia
      and invasive cancer showed an increase with age, with the 60-year-olds group
      reaching the highest. The detection rates on the above said diseases were 7.72%
      (198/2565), 2.07% (53/2565), 1.29% (33/2565), 0.51% (13/2565) respectively. The
      detection rates on mild, moderate or severe esophageal hyperplasia varied in
      different years and with statistically significant differences (P < 0.001) but
      did not show any obvious trend of changing. Geographical distribution of mild
      esophageal hyperplasia, moderate esophageal hyperplasia, severe esophageal
      hyperplasia also significantly varied in different villages (P < 0.001). The
      highest detection rate in the mountainous villages was seen the highest while the
      detection rate of village from hilly areas was the lowest. CONCLUSION: There were
      considerable numbers of patients with precancerous lesions in the general
      population from the high risk areas. The detection rate of esophageal cancer in
      the mountain residents was higher than the rate in the hilly areas. Men and the
      elderly were the key populations calling for esophageal cancer prevention
      programs to be carried out.

PMID- 22967329
TI  - [Related factors on patients with depression related to Alzheimer's disease based
      on the improved cumulative logistic regression].
AB  - OBJECTIVE: To explore the determinants of Alzheimer's disease (AD) patients with
      depression. METHODS: The degree of depression on AD patients was assessed by the
      geriatric depression scale. Improved cumulative logistic regression (ICLR) was
      used to analyze the determinants of AD patients with depression. RESULTS: 196 AD
      patients were investigated. Among the 196 AD patients, there were 60 (30.6%)
      males and 136 (69.4%) females, at 58 - 89 years of age (72.3 +/- 6.0). Physical
      activity, diabetes, MoCA, hearing, economic sources and alcohol were related to
      the degree of depression of AD patients (P < 0.10). The difference between
      "normal" and "mild depression" was smaller than difference between "mild
      depression" and "severe depression". CONCLUSION: AD patients with mild depression
      were the target population for prevention and they were influenced by several
      factors listed above.

PMID- 22967330
TI  - [Relationship between factors as sensation seeking, general self-efficacy and
      deviant peers with refusal skills among middle school students].
AB  - OBJECTIVE: To explore the relationship of sensation seeking, self-efficacy,
      deviant peers and refusal skills related to strategy on drugs among middle school
      students. METHODS: A total of 502 students from two high schools and two
      vocational schools in Baise city were recruited with age distribution between 14
      and 20 years. The study objects were asked to fill the sensation seeking scale,
      the general self-efficacy scale questionnaire on drug refusal strategies and
      behavior among peers. RESULTS: (1) Adolescents were more likely to use the Refuse
      (78.29%) and Leave strategy (77.89%) for initial drug offers and follow-up drug
      offers; (2) The general self-efficacy was negatively associated with the Explain
      and Leave strategies for initial drug offers and Explain strategy for follow-up
      drug offers. Sensation seeking was negatively related to the strategies on
      Explain and Leave for initial drug offers and follow-up drug offers. Peer
      influence was positively associated with both Refuse and Leave strategies for
      initial drug offers and follow-up drug offers; (3) RESULTS: from the logistic
      regression analysis showed that self-efficacy and sensation seeking were
      significant variables that could predict the results from the use of Explain
      strategy (beta = -0.055 and -0.029) for both initial drug refusals and follow-up
      drug refusals and the use of Leave strategy (beta = -0.057 and -0.041) for
      initial drug refusals. CONCLUSION: There were significant effects of sensation
      seeking and self-efficacy in predicting Explain or Leave strategies for drug
      refusals among middle students.

PMID- 22967332
TI  - [Investigation on the prevalence of high risk human papillomavirus and cervical
      cancer among adult women, in Shenzhen].
AB  - OBJECTIVE: To investigate the prevalence of high risk human papillomavirus (HPV)
      genital infection and cervical cancer in adult women from Shenzhen. METHODS:
      Cluster sampling was used to investigate the prevalence of HPV infection and
      cervical cancer from women aged 20 - 59 years old living in Luohu, Futian,
      Nanshan, Longgang and Baoan districts in Shenzhen from April 2006 to April 2010.
      All women were detected for liquid-based cytology test (LCT) or Thinprep
      cytologic test (TCT) and high-risk HPV-DNA test with hybrid capture II (HC-II).
      All women with >= ASC-US by cytology and/or a positive HC-II test were asked to
      return for colposcopy and four-quadrant biopsy. Endocervical curettage was
      performed. Pathological finding were used as the gold standard of the diagnosis
      of cervical intraepithelial neoplasia. RESULTS: 10 210 women were involved in the
      study and 10 017 of them having completed data. The overall positive rate of high
      risk HPV-DNA was 16.29%. HPV positive rates in 20-, 30-, 35-, 40-, 45-, 50-59 age
      groups were 17.37%, 15.59%, 16.33%, 14.74%, 17.16% and 17.98%, respectively. The
      curve of HPV infection rates in different age groups appeared a 'W' shape. HPV
      infection rates in the 25-years-olds and 50-59 year-olds groups were
      significantly higher than the other age groups (chi(2) = 4.50, P = 0.03). The
      overall prevalence rate of cervical intraepithelial lesions (CIN) was 7.52%, of
      which the prevalence rates of low-grade cervical intraepithelial lesions (CIN I)
      was 5.32% high-grade cervical intraepithelial lesions (CIN II/III) was 2.21%,
      cervical cancer was 0.12%. The prevalence of CIN I was significantly higher than
      the CIN II/III (chi(2) = 134.15, P < 0.001). The prevalence of cervical cancer in
      45-age group was 0.12%, the highest. HPV infection rates increased with the
      grades of cervical lesions including women without CIN as 44.31%, in CINI as
      70.73%, in CINII as 86.73%, and in CIN III as 96.75% and in cancer as 100.00%.
      The HPV infection rates were different in districts (chi(2) = 17.81, P = 0.03),
      with Futian and Luohu higher than those of Nanshan, Longgang and Baoan district.
      The prevalence rate of CIN in Baoan was lower than other districts. The CIN
      prevalence rates were not significantly different among the other districts of
      Shenzhen (chi(2) = 4.84, P = 0.18). CONCLUSION: The prevalence of cervical cancer
      was low in adult women living in Shenzhen, with cervical lesions still in the
      early stage. Prevention of HPV infection and treatment of CIN were the key points
      for the prevention of cervical cancer.

PMID- 22967331
TI  - [Prevalence and risk factors on the resistance related to second-line drugs among
      multi-drug resistant tuberculosis cases in Shanghai, China].
AB  - OBJECTIVE: To determine the prevalence and risk factors on second-line drug
      resistance in patients with multidrug resistant tuberculosis (MDR-TB) in
      Shanghai, China. METHODS: All pulmonary TB patients with sputum culture
      positivity detected in Shanghai during January to December, 2009, were enrolled.
      All of the pretreatment sputum-positive cultures samples were tested for routine
      specimen identification and routine drug susceptibility testing for first-line
      drugs (Isoniazid, Rifampin, Ethambutol and Streptomycin). Drug susceptibility
      testing on second-line anti-TB drugs (Ofloxacin, Amikacin, Kanamycin,
      Capreomycin, P-aminosalicylic acid and Prothionamide) was routinely performed on
      isolates of Mycobacterium (M.) TB with MDR. Logistic regression analysis was
      conducted to determine the risk factors regarding second-line drug resistance.
      RESULTS: A total of 1867 patients infected with M. TB isolates were diagnosed at
      the TB hospitals/clinics in Shanghai during the study period, of whom 112 (6.0%)
      were MDR-TB, in which 58 cases (51.8%) showed resistant to at least one of the
      second-line drugs tested and 10 cases belonged to extensively drug-resistant. In
      the multivariate analyses, MDR-TB patients who were aged 45 - 59 years (aOR =
      4.76, P = 0.001), with sputum smear positivity (aOR = 6.51, P = 0.026) were
      significantly more likely to show resistance to second-line drugs. CONCLUSION:
      The prevalence of second-line drug resistance among MDR-TB patients was high in
      Shanghai. MDR-TB patients who were under age of 45 - 59 years and with sputum
      smear positivity would represent important common risk factors for the resistance
      to second-line drugs.

PMID- 22967333
TI  - [Application of SF-36 scale among patients with advanced-schistosomiasis in
      Jiangsu province].
AB  - OBJECTIVE: To understand the reliability and validity on SF-36 scale and the
      quality of life (QoL) among patients with advanced-schistosomiasis in Jiangsu
      province. METHODS: Cluster sampling method was used to choose 586 advanced
      schistosomiasis patients who were registered in Jiangsu province. Questionnaire
      including SF-36 module, was used for face to face interview on the patients.
      Statistical analyses were made to assess the results, including correlation
      analysis, reliability analysis, factor analysis, t-test and one-way ANOVA.
      RESULTS: The split-half reliability coefficient was 0.92, P < 0.001 and the
      internal consistency reliability was 0.90, with the range of Cronbach' alpha
      coefficient on each dimension was from 0.69 to 0.98. Through principal component
      analysis, two factors were identified, with the accumulative contribution rate as
      67.37%. SF-36 showed certain discriminant validity to distinguish groups in
      different economic levels. Compared with the domestic norm data, the scores of SF
      36 on those patients were generally lows. CONCLUSION: SF-36 had good reliability
      and good criterion validity, with a certain degree of discriminant validity, but
      with poor constructs validity. Level of QoL of patients with advanced
      schistosomiasis in Jiangsu was low because of being chronically ill, that called
      for more strategies to improve the QoL of patients.

PMID- 22967334
TI  - [Spatial clustering and changing trend of hand-foot-mouth disease during 2008
      2011 in China].
AB  - OBJECTIVE: The purpose of this study was to explore the spatial clustering,
      specific clustering areas, as well as changing trend of clustering areas of hand
      foot-mouth disease (HFMD). METHODS: Exploratory spatial data analysis (ESDA) was
      used to conduct spatial statistical analyses for the HFMD using 2008 - 2011 data
      at both provincial and county/district levels. RESULTS: The Global Moran's I
      coefficients appeared to be 0.3336, 0.6074, 0.3372, 0.4620 and 0.4367 for 2008 -
      2011 and for the combined 4 years, respectively. The corresponding P-values were
      0.002, 0.001, 0.004, 0.001 and 0.001 respectively, when using the Monte Carlo
      tests with all the P-values less than 0.05. Moran's I coefficients ranged between
      0.3 and 0.7, showing the appearance of moderate or higher clustering nature.
      Based on the results from nationwide analyses on clustering areas at the
      county/district levels between 2008 and 2011 (Moran's I = 0.5198, P = 0.001), it
      appeared a moderate clustering nature. When local autocorrelation analysis was
      applied at the provincial level, 3 hot spot areas in Beijing, Tianjin and
      Shanghai cities in 2008; 7 hot spot areas in Beijing, Tianjin, Hebei, Shanxi,
      Shanghai, Jiangsu and Shandong in 2009; four hot spot areas: Beijing, Tianjin,
      Guangdong and Guangxi; five hot spot areas: Fujian, Jiangxi, Hunan, Guangdong and
      Guangxi in 2011, were discovered. 390 hot-spot counties/districts were found
      through local autocorrelation analyses using the three-year data of 2008 to 2010.
      CONCLUSION: Spatial clustering nature of HFMD incidence between 2008 and 2011 in
      China appeared to be moderate or high, with the clustered areas a north to south
      shifting trend. However, further investigation was in need to address this
      changing trend.

PMID- 22967335
TI  - [Epidemiological characteristics and temporal-spatial clustering analysis on hand
      foot-mouth disease in Jiangsu province, 2009 - 2011].
AB  - OBJECTIVE: To analyze the epidemic characteristics of hand-foot-mouth disease
      (HFMD) in Jiangsu province. METHODS: We downloaded the case-data of HFMD in
      Jiangsu province during 2009 - 2011 from the Chinese National Notifiable
      Infectious Disease Reporting System, and made a comprehensive analysis on the
      epidemiological features of it with descriptive epidemiological methods and
      retrospective space-time permutation scan statistics. RESULTS: A total of 285 414
      cases were reported in Jiangsu, from 2009 to 2011, with an annual incidence of
      122.66 per 100 000. There were 3686 severe cases in the 3 years a cumulatively,
      accounting for 1.29% of the total. Proportion of the cases being 5 years old or
      even younger was 93.64%. Scatteredly living children accounted for 64.08% of the
      total cases and 78.65% of the severe cases, respectively. The epidemics of HFMD
      were visible in each city of Jiangsu province, with a lowest annual incidence
      rate of 44.02 per 100 000 and a highest one up to 202.90 per 100 000. Regions as
      Suzhou, Nanjing, Wuxi had the highest incidence in the province, with cases in
      these three areas occupying almost 40% of all. The numbers of severe cases in
      Suqian and in Yancheng cities increased by 339.22% and 328.33% in 2011 compared
      to in 2010, respectively, and the rates of increase in these two cities were much
      higher than those in the other regions. Two peaks of incidence were observed
      every year, with the highest occurring between April and June and the second
      occurring in November. The spatial-temporal distribution of HFMD was not random
      in Jiangsu province, from 2009 to 2011. Clusters for general cases in August and
      7 clusters for severe cases were detected, respectively. 12 359 cases of HFMD
      were laboratory confirmed in the said 3 years, including 10 414 common cases and
      1945 severe cases. EV71 and CoxA16 accounted for 43.49% and 37.07% of common
      cases, respectively. In terms of the severe cases, the ratios were 80.82% and
      5.96%, respectively. CONCLUSION: HFMD was highly endemic in Jiangsu province, and
      the situation of prevention and control for it is still grim. Scatteredly living
      children of 5 years old or younger were the major population at risk, and the
      epidemic in different regions and seasons was different. EV71 and CoxA16 were the
      major etiologic agents, but the etiologic constitute showed seasonal changes.

PMID- 22967336
TI  - [Ecological-geographic landscapes of natural plague foci in China VI. Biological
      characteristics of natural vectors of Yesinia pestis].
AB  - OBJECTIVE: To characterize the biological characteristics of natural vectors of
      Yersinia (Y.) pestis in China. METHODS: Species and genera of natural vectors of
      Y. pestis in China and their faunal distribution were characterized with modern
      insect taxonomic techniques. The ecological roles of natural vectors of Y. pestis
      in natural plague foci were determined according to insect ecological
      experiments. RESULTS: There were 63 species of natural vectors of Y. pestis
      including 28 major reservoirs and 35 secondary ones. CONCLUSION: The biology
      characteristics of major vectors on Y. pestis and their roles in natural plague
      foci were defined.

PMID- 22967337
TI  - [Identification of snail habitats in the Poyang Lake region, based on the
      application of indices on joint normalized difference vegetation and water].
AB  - OBJECTIVE: With Landsat TM remote sensing images, snail habitats in Poyang Lake
      region were identified, using two indices: the modified normalized difference
      water index (MNDWI) and the normalized difference vegetation index (NDVI).
      METHODS: Two Remote sensing images of both wet and drought seasons in Poyang Lake
      region were obtained. MNDWI and NDVI were extracted from the images respectively,
      to present the regions of "water in summer and land in winter" and the coverage
      of vegetation. By overlaying those two regions, the areas of potential snail
      habitats were drawn. Finally, sensitivities and specificities of the recommended
      methods were assessed and compared to that of the traditional methods for the
      sake of extracting the areas of snail habitats. RESULTS: The threshold values of
      MNDWI for the wet and drought seasons were 0.34 and 0.58, respectively and the
      threshold value for NDVI of the drought season was 0.02. Sensitivity and
      specificity of our method were 95% and 100%, respectively, higher than the
      conventional approach (se. = 75%, sp. = 100%). CONCLUSION: Joint application of
      MNDWI and NDVI seemed a better method to detect the snail habitats and could be
      used for the quantitative and automatic surveillance program on snails.

PMID- 22967338
TI  - [Genetic analysis on S segment of hantaviruses in rodent hosts from Wuhan area,
      Hubei province].
AB  - OBJECTIVE: To investigate the infection and genotype of hantaviruses in rodents
      from Wuhan area, Hubei province. METHODS: Rodents were trapped in fields and
      residential areas of Xinzhou and Jiangxia districts of Wuhan in autumn and winter
      seasons, from 2000 to 2003 and from 2009 to 2011. Trapped rodents were
      identified, and hantavirus antigens were detected in the lung tissues with
      indirect immunofluorescence assay (IFA). Partial S segment sequences were
      amplified with RT-PCR in hantavirus antigen positive samples and then sequenced.
      Phylogenetic tree was constructed to analyze the genetic characteristics of
      hantaviruses. RESULTS: From 2000 to 2003, 437 rodents were trapped, with 24
      (5.49%) lung tissues showed hantavirus antigen positive. From 2009 to 2011, 173
      rodents were trapped and 7 (4.05%) were hantavirus antigen positive. Rattus
      norvegicus were the dominant species of rodents. Partial S segment sequences were
      amplified from 22 samples with Hantaan and Seoul viruses specific primers and
      sequenced. Partial S segments of Seoul viruses (nucleotide 588 - 1147) were
      amplified from 17 rodents (13 R. norvegicus and 4 Apodemus agrarius). Seven of
      these sequences belonged to 3 genetic lineage, while two novel genetic lineages
      were formed by 9 and 1 sequences, respectively. Partial S segments of Hantaan
      viruses (nucleotide 615 - 1141) were amplified from 5 A. agrarius. One of these
      sequences belonged to 7 genetic lineages, and 4 sequences formed one novel
      genetic subtype. CONCLUSION: Hantaan and Seoul viruses co-circulated in Wuhan
      area, Hubei province. Novel genetic lineages were identified in this study and
      Seoul virus might have caused spillover infection in A. agrarius.

PMID- 22967339
TI  - [Genetic characteristics of hantaviruses carried by Microtus maximowixzii in
      Yakeshi of Inner Mongolia, China].
AB  - OBJECTIVE: To analyze the viral genetic characteristics of hantaviruses carried
      by Microtus maximowixzii in Yakeshi of Inner Mongolia Autonomous Region and its
      relationship with Hantaan virus (HTNV) and Seoul virus (SEOV) viruses as well as
      to identify the natural host of Khabarovsk virus (KHAV). METHODS: HV specific
      RNAs were detected by RT-PCR. Complete S and M segment were amplified from the
      RNA-positive samples. Phylogenetic analysis were performed to estimate the
      genetic characterization and the relationship with other hantaviruses. RESULTS:
      Fifty two Microtus maximowixzii voles were captured in Yakeshi areas. Of those
      voles, hantaviral RNA was tested positive in 5 samples (9.62%). Complete S and M
      segments sequences were obtained from 5 and 2 lung samples, respectively. The
      complete S segment was consisted of 1848 to 1861 bp, and the M segment consisted
      of 3662 bp. These viruses were closely related to each other with 92.5% - 96.4%
      for the S segment sequences and 88.9% - 95.4% for the M segment sequences. They
      shared a higher identity with KHAV found previously in Yakeshi and KHAV of
      Russia. However, they were obviously different from the other hantavirus species.
      The 5 strains had the consistent secondary structure of nucleocapsid protein (NP)
      and glycoprotein (GP). When further comparing their secondary structures with
      those of HTNV and SEOV, our results indicated that there were no obvious
      differences in NP between KHAV and both HNTV, SEOV but with obvious difference in
      GP. Based on the S and M segment sequences, phylogenetic analyses revealed that
      these 5 strains clustered together with KHAV and formed a distinct lineage.
      Furthermore, all known KHAV strains could be divided into two small branches with
      a nucleotide divergence more than 5.3%. CONCLUSION: Our research data revealed
      that KHAV was highly endemic among Microtus maximowixzii in Yakeshi area which
      supported the notion that Microtus maximowixzii had been the natural host of KHAV
      in the area.

PMID- 22967340
TI  - [HIV-1 subtype and the distribution in Yunnan province].
AB  - OBJECTIVE: To understanding the genetic subtype and its population and regional
      distribution of HIV-1 strains circulating in Yunnan province. METHODS: 788 plasma
      specimens collected in 2008-2009 from 15 distracts of Yunnan, were enrolled.
      Viral RNA were extracted and subjected to RT-PCR. 1584 bp full length gag gene,
      3147 bp full length pol gene and 558 bp env (C2V3) fragment were amplified and
      directly sequenced. Full length gag and pol genes were connected together as a
      complete genetic region (location on HXB2: 790 - 5096) for genotyping. RESULTS:
      Of the 788 plasma specimens, a total number of 1728 genomic sequences including
      599 gag, 564 pol and 525 env (C2V3) were successfully amplified and sequenced,
      with genotype of 617 samples identified. The subtypes of HIV-1 strains circulated
      in Yunnan were with the order of constituent ratio CRF08_BC (50.2%), CRF01_AE
      (25.0%), unknown recombinant forms (10.2%), CRF07_BC (9.2%), subtype C (2.9%) and
      subtype B (B') (2.4%). The distributions of subtypes showed significant regional
      differences and could be roughly divided into two forms:the CRF08_BC predominant
      areas represented by Lincang and Kunming, and the areas with CRF08_BC together
      with CRF01_AE coexistence, represented by Dehong and Xishuangbanna. The unknown
      recombinant forms accounted for more HIV infection in ethnic minorities (17.0%)
      than in ethnic Han (6.7%, P < 0.01). The distribution of subtypes varied
      significantly in the two primary routes of transmission for those infected
      through heterosexual contact. CRF08_BC and CRF01_AE were the dominant subtypes,
      accounting for 52.7% and 29.1% respectively. However, in IDUs, CRF08_BC strains
      accounted for half of the infection, while only 4.5% of the infections were
      caused by CRF01_AE, CRF07_BC while the unique recombinant forms were responsible
      for 15.5% infections. Of the 63 unknown recombinant forms, most (74.6%) were B
      (B') recombinant with C, while 25% were mosaic B and/or C fragments on the bases
      of CRF01_AE genome. CONCLUSION: The subtypes of HIV-1 strains circulated in
      Yunnan were complicated under the significant differences of regions, ethnics or
      routes of transmission.

PMID- 22967341
TI  - [Association between serum bisphenol-A and recurrent spontaneous abortion: a 1:2
      case-control study, China].
AB  - OBJECTIVE: This study was to investigate the association between serum Bisphenol
      A (BPA) and unexplained recurrent spontaneous abortion (RSA). METHODS: A hospital
      based 1:2 matched case-control study was conducted.Sixty-two patients with
      unexplained recurrent abortion were included and matched with 2 normal controls
      by factors as age (+/- 2 years), living in the same district and the same
      gestational age.The levels of BPA in serum for 62 cases and 108 controls were
      detected under high performance liquid chromatography after fluorescent
      derivatization. Levels of serum BPA in each case was compared with that in
      control of age, BMI, education levels, occupation, exposure for passive smoking.
      RESULTS: The values of serum BPA in cases and controls were (0.009 +/- 0.002) and
      (0.004 +/- 0.012) ug/ml, respectively. The levels of serum BPA in cases was
      significantly higher than in controls (Z = 3.506, P = 0.0005). After adjusted by
      age, BMI, education levels, occupation, passive smoking history and other
      factors, when compared to BPA below 0.004 ug/ml. The adjusted ORs were 4.39 (1.15
      - 16.71) for BPA levels between 0.004 ug/ml and 0.012 ug/ml, and 4.95 (1.77 -
      13.82) for BPA over 0.012 ug/ml. The risk of unexplained recurrent spontaneous
      abortion increased progressively with the growth of serum BPA levels (chi(2) =
      9.179, trend test P = 0.0024). There were significant differences on BPA among
      controls that with histories of two, three or more abortions (the levels were
      0.004, 0.008, 0.018 ug/ml, respectively, F = 8.92, P = 0.0002). CONCLUSION: High
      BPA level might be associated with unexplained recurrent spontaneous abortion.

PMID- 22967342
TI  - [Relations between serum homocysteinemia and carotid artery plaques].
AB  - OBJECTIVE: To explore the relation between homocysteinemia (HCY) and carotid
      artery plaque. METHODS: Subjects were derived from a cohort of Kailuan study,
      which was a community-based and cross-sectional. From June 2010 to June 2011, a
      total of 5852 subjects were selected from 101 510 working or retired employees at
      the Tangshan Kailuan Company in 2006 - 2007. Data was extracted from the results
      of health examination on the employees. Selecting process was carried out by
      those staff working on the clinical trials on stroke and from the research center
      of Tiantan Hospital, Capital Medical University. Subjects who were beyond 40
      years of age but without histories as previous stroke, transient ischemic attack
      (TIA) or myocardial infarction were included and identified, to take part in the
      study through stratified random sampling. Finally, 5440 eligible subjects were
      enrolled and data from 5377 subjects were analyzed. All the information was
      obtained through unified questionnaire, blood tests and carotid artery
      ultrasonography. Multivariate logistic regression was used to analyze the factors
      related to carotid artery plagues. RESULTS: (1) The baseline results showed that
      the average age of the subjects (n = 5377) was 55.18 +/- 11.78 years old with
      3215 as males. All the subjects were divided into three groups by tertiles of
      HCY, with 1771 subjects in the first quartile group (HCY < 11.00 umol/L), 1814 in
      the second quartile group (11.00-16.98 umol/L) and 1792 in the third quartile
      group (>= 16.98 umol/L). 2300 subjects were identified as having carotid artery
      plaques. (2) The prevalence rates of carotid artery plaques in the three groups
      were 29.9%, 43.3% and 55.0% respectively. (3) After multivariable adjustment, the
      third quartile HCY was still serving as a risk factor, affecting the formation of
      carotid artery plaques, with the OR values as 1.344 (95%CI: 1.134 - 1.594).
      CONCLUSION: High HCY was related to the increased prevalence of carotid artery
      plaque and thus served as a risk factor for carotid artery plaque.

PMID- 22967343
TI  - [Clinical and histo-pathological characteristics of 2874 cases with chronic
      kidney diseases in Southern parts of Hebei province].
AB  - OBJECTIVE: The aim of this study was to analyze the characteristics of patients
      with chronic kidney disease (CKD) in Southern parts of Hebei province. METHODS:
      Records of 2874 CKD patients during January, 2008 to May, 2011 were
      retrospectively reviewed. Demographic, clinical and histo-pathological data were
      analyzed and compared to ones from the past five years. RESULTS: The age
      distribution of the groups was between 16 and 84 years old, with 62.39% of them
      between 20 and 50. All patients underwent renal biopsy that with primary
      glomerulonephritis occurring in 1966 cases (68.41%), secondary glomerulonephritis
      in 826 cases (28.74%). The frequently seen pathological patterns were IgA
      nephropathy (IgAN), membranous nephropathy (MN) and minimal change disease (MCD)
      in proper order in the former group while Henoch-Schonlein purpura nephritis
      (HSPN) and lupus nephritis (LN) were seen in the latter group. Comparing to data
      of the past five years, the incidence rates of MN, MCD and HBV-GN increased to
      16.84%, 15.73% and 4.41% respectively, but all IgAN, HSPN and LN had respectively
      decreased to 24.70%, 5.50% and 6.65%. MN, IgAN, MCD were commonly appeared in
      histo-pathological patterns among patients over 50 years of age. CONCLUSION: IgAN
      was still the most commonly seen renal disease. Compared to data of the past five
      years, the incidence rates of MN, MCD and HBV-GN showed an increase at different
      levels. Epidemiological and pathological pattern of patients with CKD in Southern
      Hebei province had only mild changes over the last 3 years.

PMID- 22967344
TI  - [Improvement in blood glucose fluctuations of insulin-treated type 1 diabetic
      patients with additional use of acarbose and assessed by continuous blood glucose
      monitoring program].
AB  - OBJECTIVE: To investigate the effect of combined use of insulin and acarbose on
      glucose excursion in type 1 diabetic patients. METHODS: 120 cases were randomly
      divided into control group and observation group. The control group received
      preprandial ultra-short effect insulin and long-acting insulin before bedtime
      while the observation group received acarbose 50 mg added to the medicine taken
      by the control group. Continuous Glucose Monitoring System (CGMS) was used to
      watch the blood glucose fluctuations. Data related to blood glucose level,
      glucose excursions after meals and hypoglycemia at night were compared between
      patients in the two groups. RESULTS: The average blood glucose (9.37 +/- 1.70)
      mmol/L, the largest amplitude of glycemic excursions (LAGE) (11.42 +/- 2.73)
      mmol/L, hyperglycemia-area under curve 0.89 +/- 0.54, mean amplitude of glycemic
      excursions (MAGE) (5.13 +/- 2.23) mmol/L, M-value (18.93 +/- 11.43) mmol/L and
      insulin dosage (42.11 +/- 14.42) U/day of observation group were significantly
      lower than in the control group (P < 0.05). Glucose excursions after meals and
      the times (0.33 +/- 0.50)/day, the maintenance time (43.75 +/- 43.50)/min and low
      glycemic index (LBGI) (0.005 +/- 0.002) mmol/L of hypoglycemia at night were also
      significantly lower than in the control group, with statistically significant (P
      < 0.05) differences. CONCLUSION: The blood glucose fluctuation was significantly
      improved, with the decrease of insulin dosage while both glucose excursions and
      hypoglycemia at night reduced in patients with type1 diabetes mellitus after the
      acarbose treatment.We suggested that this program deserve further observation.

PMID- 22967345
TI  - [A Meta-analysis on tea drinking and the risk of lung cancer in Chinese
      population].
AB  - OBJECTIVE: To examine the association between tea drinking and the risk of lung
      cancer in Chinese population. METHODS: All relevant published articles in Chinese
      and English literature database were identified. Meta-analysis was conducted.
      Combined odds ratio (OR) and 95% confidence interval (CI) were calculated to
      estimate the associations and dose-response relationship between tea drinking and
      the risk of lung cancer. RESULTS: Twelve studies were included. An inverse
      association with lung cancer was observed on tea drinkers when compared to non
      tea drinkers (OR = 0.66, 95%CI: 0.49 - 0.89). CONCLUSION: Tea drinking might
      serve as a protective factor on lung cancer in the Chinese population.

PMID- 22967346
TI  - [Cost-utility analysis on universal childhood hepatitis A vaccination in regions
      with different anti-HAV prevalence rates of China].
AB  - OBJECTIVE: To explore the inputs and outputs of areas with different anti-HAV
      prevalence rates on universal childhood vaccination, and to provide a scientific
      basis for the formulation of the immunization strategy. METHODS: Since hepatitis
      A vaccination was scheduled at 12 and 18 months of age for all the healthy
      children, a single cohort including 1 000 000 individuals was formed in 2009,
      using the Chinese inactivated vaccine. Decision analysis was used to build Markov
      decision tree model. The universal childhood hepatitis A vaccination was compared
      with non-vaccination group to evaluate the number of symptomatic infection,
      hospitalization, death, quality-adjusted life years (QALYs) lost, and the
      incremental cost-utility from the health system and the societal perspectives.
      Outcomes of the vaccination for the next 70 years were also predicted. The
      process of analysis was run separately in five regions defined by the anti-HAV
      prevalence rates (around 50%, 50% - 69%, 70% - 79%, 80% - 89% and > 90%).
      Sensitivity analysis was performed to test the stability or reliability of the
      results, and to identify sensitive variables. RESULTS: The study projected that,
      in the lowest, lower, and intermediate infection regions, the cost and output
      indicators of universal childhood hepatitis A vaccination were all lower than non
      vaccinated group. Universal vaccination could gain QALYs and save both costs from
      the health system or the society. In the regions with higher infection rate, the
      output indicators of universal childhood hepatitis A vaccination were lower than
      in those non-vaccinated groups, except for the number of death due to hepatitis
      A, which had a 20 cases of increase. The model also predicted that in the highest
      infected region, universal vaccination would increase 4 560 814 and 5 840 430 RMB
      Yuan in the total costs from both the health system and the societies,
      respectively, when compared to the non-vaccination groups. Universal vaccination
      would also decrease the numbers of symptomatic infection, hospitalization, and
      QALYs lost, but would increase 51 deaths due to hepatitis A, and 1507, 1929 more
      RMB Yuan for each QALY gained from the health system and societal respectively,
      in the regions with highest infection rate. Sensitivity analyses discovered that
      the infection rate among those susceptible population and the proportion of those
      who initially under protection but subsequently lost their immunity every year,
      were the two main sensitive variables in the model. CONCLUSION: Our research
      discovered that the universal vaccination strategy should be based on the
      protective period of the vaccine and the anti-HAV prevalence in different endemic
      areas.

PMID- 22967347
TI  - [Progress on the research regarding the epidemiology of hepatitis C].

PMID- 22967348
TI  - Kabiramide L, a new antiplasmodial trisoxazole macrolide from the sponge
      Pachastrissa nux.
AB  - An extensive search for the trisoxazole macrolides in the Thai specimen of the
      sponge Pachastrissa nux led to the isolation of a new kabiramide derivative,
      kabiramide L (1) and the previously reported kabiramide I (2). Both macrolides
      had a moderate antiplasmodial activity against Plasmodium falciparum K1 with
      IC50s of 2.6 and 4.5 uM, respectively. To date, P. nux has been the only known
      source of the trisoxazole macrolides bearing the 30-enone moiety. Both compounds
      were also added to the list of chemicals postulated to play a defensive role in
      the P. nux sponge.

PMID- 22967349
TI  - Conformational analyses of bacillomycin D, a natural antimicrobial lipopeptide,
      alone or in interaction with lipid monolayers at the air-water interface.
AB  - Bacillomycin D is a natural antimicrobial lipopeptide belonging to the iturin
      family. It is produced by Bacillus subtilis strains. Bacillomycin D is
      characterized by its strong antifungal and hemolytic properties, due to its
      interaction with the plasma membrane of sensitive cells. Until now, only few
      limited analyses were conducted to understand the biological activities of
      bacillomycin D at the molecular level. Our purpose was to analyze the
      conformation of bacillomycin D using IR spectroscopy and to model its
      interactions with cytoplasmic membranes using Langmuir interfacial monolayers.
      Our findings indicate that bacillomycin D contains turns and allow to model its
      three-dimensional structure. Bacillomycin D formed a monolayer film at the air
      water interface and kept its turn conformation, as shown by polarization
      modulation infrared reflection absorption spectroscopy (PM-IRRAS). To identify
      the membrane lipid target of bacillomycin D, its interactions with pure lipid
      monolayers were analyzed and an original behavior of the lipopeptide toward
      cholesterol-containing monolayers was shown. This original behavior was lost when
      bacillomycin D was interacting with pure cholesteryl acetate monolayers,
      suggesting the involvement of the alcohol group of cholesterol in the lipopeptide
      cholesterol interaction.

PMID- 22967350
TI  - Preparation of poly(methyl methacrylate) microcapsules by in situ polymerization
      on the surface of calcium carbonate particles.
AB  - Poly(methyl methacrylate) (PMMA) microcapsules were prepared by the in situ
      polymerization of methyl methacrylate (MMA) and N,N'-methylenebisacrylamide on
      the surface of calcium carbonate (CaCO(3)) particles, followed by the dissolution
      of the CaCO(3) core in ethylenediaminetetraacetic acid solution. The
      microcapsules were characterized using fluorescence microscopy, atomic force
      microscopy, scanning electron microscopy, and Fourier transform infrared
      spectroscopy. The average sizes of the CaCO(3) particles and PMMA capsules were
      3.8+/-0.6 and 4.0+/-0.6 MUm, respectively. A copolymer consisting of MMA and
      rhodamine B-bearing MMA was also used to prepare microcapsules for fluorescent
      microscopy observations. Fluorescein isothiocyanate-labeled bovine serum albumin
      was enclosed in the PMMA microcapsules and its release properties were studied.

PMID- 22967351
TI  - Impact of cerebrospinal-fluid oligoclonal immunoglobulin bands and HLA-DRB1 risk
      alleles on brain magnetic-resonance-imaging lesion load in Swedish multiple
      sclerosis patients.
AB  - Approximately 95% of Nordic multiple sclerosis (MS) patients display oligoclonal
      immunoglobulin G bands (OCB) in the cerebrospinal fluid. From a cohort of 2094 MS
      patients we retrieved well-characterized data from 40 OCB-negative and 60 OCB
      positive patients, in an effort to determine whether lesion load on brain
      magnetic resonance imaging is affected by OCB status and carriage of HLA-DRB1*15
      or HLA-DRB1*04. Positivity for OCB did not increase the risk of belonging to
      higher-lesion-load groups; nor did carrying HLA-DRB1*15 or HLA-DRB1*04. A trend
      was seen, however, whereby OCB positivity conferred a two-fold risk of displaying
      higher lesion loads infratentorially.

PMID- 22967352
TI  - Theiler's murine encephalomyelitis virus induced phenotype switch of microglia in
      vitro.
AB  - The present in vitro study aimed to define the involvement of astrocytes and
      microglia in the initial inflammatory response of Theiler's murine
      encephalomyelitis (TME), a virus-induced mouse model of multiple sclerosis, and
      whether intralesional microglia exert pro- (M1) or anti-inflammatory (M2) effects
      following TME virus (TMEV) infection. Therefore astrocytes and microglia were
      purified from neonatal murine brains and inoculated either with TMEV or mock
      solution. Gene expression of IL-1, IL-2, IL-10, IL-12, TNF, TNF receptors (TNFR1,
      TNFR2), TGFbeta1, IFNgamma and transcription factors NF-kappaB (p50, p65) and AP
      1 (c-jun, c-fos) were quantified using RT-qPCR at 6, 48, and 240h post infection
      (hpi). In addition, IL-1, IL-10, IL-12, TNF and TGFbeta1 mRNA transcripts were
      investigated at 168 hpi in TMEV- and mock-infected SJL/J mice. Overall in vitro
      astrocytes showed a significant higher amount of viral RNA compared to microglia.
      In addition, TMEV-infected astrocytes showed higher numbers of IL-1, IL-12 and
      TNF transcripts at 48 hpi. In microglia high IL-10 and low IL-12 mRNA levels were
      detected at 48 hpi, while the opposite was the case at 240 hpi. In addition, TNF
      mRNA was increased in microglia at 240 hpi. In addition, the observed up
      regulation of IL-1, IL-12 and IL-10 in the early phase of TME in vivo
      substantiates the relevance of these cytokines during the disease induction.
      Summarized data indicate that TMEV infection of microglia induces a switch from
      the anti-inflammatory (M2) during the early phase to the pro-inflammatory (M1)
      phenotype in the later phase of the infection. The simultaneous expression of TNF
      and its receptors by both cell types might generate autocrine feedback loops
      possibly associated with pro-inflammatory actions of astrocytes via TNFR1.

PMID- 22967353
TI  - Possible transmission of human immunodeficiency virus-1 infection from an elite
      controller to a patient who progressed to acquired immunodeficiency syndrome: a
      case report.
AB  - INTRODUCTION: Most individuals infected with human immunodeficiency virus-1, in
      the absence of antiretroviral therapy, exhibit persistent virus replication and
      declining CD4+ cell numbers, and progress to acquired immunodeficiency syndrome
      within 10 years of infection. Elite controllers are rare individuals with human
      immunodeficiency virus-1 infection who can maintain undetectable plasma virus
      levels and remain asymptomatic without antiretroviral therapy. It has been
      proposed that elite controllers benefit from being infected with attenuated human
      immunodeficiency virus-1 variants. CASE PRESENTATION: A 31-year-old African woman
      presented with human immunodeficiency virus-1 infection during pregnancy and was
      diagnosed with acquired immunodeficiency syndrome. Subsequently, her husband, a
      31-year-old African man, was tested and found to be seropositive for human
      immunodeficiency virus-1. His plasma human immunodeficiency virus-1 ribonucleic
      acid level was found to be below the limit of detection of the clinical assay.
      CONCLUSION: This report provides evidence for the first described case of human
      immunodeficiency virus-1 infection possibly transmitted from an elite controller
      to a patient who progressed to acquired immunodeficiency syndrome. This
      observation strengthens the case against avirulence as a mechanism that protects
      elite controllers.

PMID- 22967355
TI  - Is retinoic acid-related orphan receptor-alpha (RORA) a target for gene
      environment interactions contributing to autism?
AB  - It is becoming increasingly clear that gene-environment interactions are risk
      factors for autism. However, there is limited information regarding the
      susceptibility of specific autism candidate genes to dysregulation by
      environmental factors, and even less information on the types of environmental
      agents that may lead to increased risk for autism. Based on our published
      studies, I propose that the demonstrated responsiveness of RORA to sex hormones
      makes it a prime target for disruption by endocrine disrupting compounds.

PMID- 22967356
TI  - Atypical scabies presenting as annular patches.
AB  - Scabies is a common parasitic disease that can be recognized by the development
      of itchy lesions and a predilection for certain places on the body. It may
      infrequently present with patchy lesions. We report a patient with well-defined
      annular patches. Histopathology showed an egg of the scabies mite in the
      epidermis. Treatment with permethrin cream resulted in complete resolution of her
      disease. 

PMID- 22967357
TI  - Microsatellite instability in Marek's disease virus infected primary chicken
      embryo fibroblasts.
AB  - BACKGROUND: Marek's disease virus (MDV), an oncogenic alpha-herpes virus, causes
      a devastating disease in chickens characterized by development of lymphoblastoid
      tumors in multiple organs. Microsatellite instability (MSI), a symptom of defect
      in DNA mismatch repair function, is a form of genomic instability frequently
      detected in many types of tumors. However, the involvement of MSI in MDV-infected
      cells has not been investigated. In this study, we determined the presence and
      frequency of MSI in primary chicken embryo fibroblasts infected with or without
      MDV strain in vitro. RESULTS: 118 distinct microsatellite markers were analyzed
      by polymerase chain reaction (PCR) in 21 samples. MSI was found in 91 of 118
      markers, and 12 out of 118 demonstrated frequency of MSI at >= 40%. 27 of 118
      microsatellite loci did not show microsatellite instability. CONCLUSIONS: These
      findings showed that MSI was a real event occurring in primary chicken embryo
      fibroblasts infected with MDV in vitro as evidenced by the high frequency of MSI,
      and may be specifically associated with genome alteration of host cells during
      MDV infected.

PMID- 22967359
TI  - Varicella zoster central nervous system vasculitis after allogeneic hematopoietic
      stem cell transplant successfully treated with cyclophosphamide.
AB  - We report the first case of varicella zoster central nervous system vasculitis,
      to our knowledge, which responded to intravenous pulses of cyclophosphamide in an
      immunocompromised child with severe and progressive disease, without sequelae.

PMID- 22967360
TI  - Synthesis of backbone P-functionalized imidazol-2-ylidene complexes: en route to
      novel functional ionic liquids.
AB  - 1-Alkyl-3-methyl-4-diphenylphosphoryl-imidazolium hydrogensulfate (4a,b) (a: R(1)
      = R(2) = Me; b: R(1) = (i)Pr, R(2) = Me) and 1-alkyl-3-methyl-4,5
      bis(diphenylphosphoryl)imidazolium hydrogensulfate (6a,c) (c: R(1) = (n)Bu, R(2)
      = Me) were obtained selectively and in good yields by oxidative desulfurization
      of 1-alkyl-3-methyl-4-diphenylphosphino-imidazole-2-thiones (2a,b) and 1-n-butyl
      3-methyl-4,5-bis(diphenylphosphoryl)imidazole-2-thione (3c) or 1,3-dimethyl-4
      diphenylthiophosphoryl-5-diphenylphosphino-imidazole-2-thione (5a), respectively,
      with hydrogen peroxide. Synthesis of phosphoryl functionalized imidazol-2-ylidene
      complexes of group VI metal pentacarbonyls (7a-9a) and (10b-12b) and
      bis(phosphoryl) functionalized imidazol-2-ylidene complexes of group VI metal
      pentacarbonyls (13c-15c) and (16a) with low steric demand (methyl, isopropyl, n
      butyl) at both N-centers was achieved through deprotonation of imidazolium salts
      (4a,b) and (6a,c), respectively,-having HSO(4)(-) as a counterion-with potassium
      tert-butoxide followed by rapid addition of metal pentacarbonyl acetonitrile
      complexes [M(CO)(5)(CH(3)CN)] (M = Cr, Mo, W). The products were unambiguously
      characterized by elemental analyses, spectroscopic and spectrometric methods, and
      in addition, by single-crystal X-ray structure studies in the cases of 4b, 8a,
      15c, and 16a; the latter two reveal imidazole ring bond distance alternation in
      contrast to 8a.

PMID- 22967354
TI  - Therapeutic approaches to preventing cell death in Huntington disease.
AB  - Neurodegenerative diseases affect the lives of millions of patients and their
      families. Due to the complexity of these diseases and our limited understanding
      of their pathogenesis, the design of therapeutic agents that can effectively
      treat these diseases has been challenging. Huntington disease (HD) is one of
      several neurological disorders with few therapeutic options. HD, like numerous
      other neurodegenerative diseases, involves extensive neuronal cell loss. One
      potential strategy to combat HD and other neurodegenerative disorders is to
      intervene in the execution of neuronal cell death. Inhibiting neuronal cell death
      pathways may slow the development of neurodegeneration. However, discovering
      small molecule inhibitors of neuronal cell death remains a significant challenge.
      Here, we review candidate therapeutic targets controlling cell death mechanisms
      that have been the focus of research in HD, as well as an emerging strategy that
      has been applied to developing small molecule inhibitors-fragment-based drug
      discovery (FBDD). FBDD has been successfully used in both industry and academia
      to identify selective and potent small molecule inhibitors, with a focus on
      challenging proteins that are not amenable to traditional high-throughput
      screening approaches. FBDD has been used to generate potent leads, pre-clinical
      candidates, and has led to the development of an FDA approved drug. This approach
      can be valuable for identifying modulators of cell-death-regulating proteins;
      such compounds may prove to be the key to halting the progression of HD and other
      neurodegenerative disorders.

PMID- 22967361
TI  - The critical role of training in protecting workers.

PMID- 22967362
TI  - Learning to take action: the goals of health and safety training.
AB  - Worker health and safety training is an important part of occupational health and
      safety programs. In the United States, governments, unions, employers, university
      programs, and health and safety advocacy organizations make training available.
      This article considers training effectiveness research conducted and supported by
      the National Institute for Occupational Safety and Health (NIOSH), and some done
      in collaboration with the Institute for Work and Health (Canada). Differing
      perspectives regarding the purpose of worker health and safety training are
      reviewed and critiqued. We assert that a focus on changing the working behaviors
      of workers exposed to hazardous conditions is less appropriate and scientifically
      rigorous than a focus on helping workers establish the power to reduce and
      eliminate workplace hazards. For training to lead to a decrease in morbidities
      and fatalities related to hazardous exposures, it needs to be integrated with
      workers' attainment of such power.

PMID- 22967363
TI  - Being on the web of unions: an interview with D'Arcy Martin, Toronto, Ontario,
      Canada.
AB  - D'Arcy Martin is a labor educator in Toronto. He started his career in adult
      education and made the transition to labor educator. He has been the Canadian
      education director for Steelworkers, Communications Workers, and the merged
      Communications, Energy and Paperworkers Union. He is also coordinator of the
      Centre for the Study of Education and Work at the University of Toronto, which
      brings together academics and unionists to research the informal learning of
      workers. In the following interview, D'Arcy talked about his experiences as a
      Canadian labor educator, how being an internationalist has influenced his views,
      and how the dynamics of power influence not only workers and their unions, but
      educators, too. D'Arcy described his work as "being on the web ... to go
      sideways, that is, to draw connections, including international ones, amongst
      people of like mind and to build collective power by inviting people to learn
      together."

PMID- 22967364
TI  - Creative mistrust.
AB  - Based on six years spent investigating worker health and safety conditions at
      U.S. Department of Energy sites that were formerly engaged in the production of
      nuclear weapons, the authors report on a set of common themes that emerged in
      their interviews with workers. The initial focus of the authors was on behavior
      based safety programs and their investigation revealed deep-seated mistrust of
      management by workers. The authors discuss the importance of trust issues for
      worker training and suggest that "creative mistrust" should be cultivated in
      training programs.

PMID- 22967365
TI  - From agricultural fields to urban asphalt: the role of worker education to
      promote California's heat illness prevention standard.
AB  - This article describes an innovative approach to reach and educate workers and
      worker advocates about California's outdoor heat illness prevention standard. In
      2010, Cal/OSHA initiated a statewide education campaign to reduce heat-related
      illnesses and fatalities and increase awareness of the standard's requirements.
      In Southern California, the UCLA Labor Occupational Safety and Health Program
      (LOSH) focused on three principal strategies of community-based outreach, popular
      education, and organizational capacity building. Central to the LOSH approach was
      the integration of health promotores into core program planning and training
      activities and the expansion of campaign activities to a wide variety of rural
      and urban workers. We describe each of these strategies and analyze the
      possibilities and constraints of worker education to support implementation of
      this standard, particularly given the vulnerabilities of the impacted workforce,
      the often precarious nature of employment arrangements for these workers, and the
      resource limitations of Cal/OSHA.

PMID- 22967366
TI  - Using hazard maps to identify and eliminate workplace hazards: a union-led health
      and safety training program.
AB  - The Institute for Sustainable Work and Environment and the Utility Workers Union
      of America worked with a professional evaluator to design, implement, and
      evaluate the results of a union-led system of safety-based hazard identification
      program that trained workers to use hazard maps to identify workplace hazards and
      target them for elimination. The evaluation documented program implementation and
      impact using data collected from both qualitative interviews and an on-line
      survey from worker trainers, plant managers, and health and safety staff.
      Managers and workers reported that not only were many dangerous hazards
      eliminated as a result of hazard mapping, some of which were long-standing,
      difficult-to-resolve issues, but the evaluation also documented improved
      communication between union members and management that both workers and managers
      agreed resulted in better, more sustainable hazard elimination.

PMID- 22967368
TI  - Beyond the classroom: a case study of immigrant safety liaisons in residential
      construction.
AB  - Latino day laborers often work at dangerous construction sites with little power
      to change conditions. We describe the development, implementation, and early
      stage results of a program to train immigrant day laborers as safety liaisons.
      These are construction workers prepared to recognize and respond to health and
      safety hazards. Based in Newark, NJ, the project involves collaboration between
      New Labor, a membership-based worker center, and university researchers and labor
      educators. Safety liaisons undergo training and receive ongoing support for their
      roles. Both qualitative and quantitative data are collected to monitor progress.
      Although lacking in formal authority, safety liaisons have prompted improvements
      at specific sites, filed OSHA complaints, and developed a local worker council.
      Participatory training methods, opportunities for leadership outside the
      classroom, and participation in project planning have strengthened liaisons'
      effectiveness, leadership skills, and commitment. The safety liaison approach
      could be adapted by worker centers and their partner organizations.

PMID- 22967367
TI  - Triangle of prevention: a union's experience promoting a systems-of-safety health
      and safety program.
AB  - After years of watching company health and safety programs fail to prevent major
      incidents, injuries, illness, and death in industrial workplaces, union health
      and safety staff and rank and file activists took up the challenge of creating a
      union-run alternative program. Named the Triangle of Prevention (TOP), the
      program successfully engages both local unions and management in incident and
      near-miss reporting and investigation, root cause analysis, recommending and
      tracking solutions, and learning and sharing lessons. In all phases, TOP uses a
      hierarchical, systems-of-safety-based approach to hazard identification,
      reporting, prevention and control while aiming to engage the union, its members,
      and all other employees of a worksite. This article explains the foundations and
      workings of this program, the role of an expansive worker-to-worker training
      regimen, and the ways in which the program has transformed workplaces.

PMID- 22967371
TI  - Championing of dementia in England.
AB  - Dementia is starting to attract attention following decades of comparative
      neglect relative to other disease areas. England has been at the forefront of
      this sea change as one of the first countries in the world to develop a National
      Dementia Strategy (in 2009). Events leading up to the publication of this
      strategy and since will be examined here together with a glimpse at the
      international landscape. 

PMID- 22967369
TI  - Novel approaches to development, delivery and evaluation of a peer-led
      occupational safety training for Latino day laborers.
AB  - Latino day laborers experience high rates of work-related injuries and are a hard
      to-reach group for safety interventions. This study describes the creation and
      implementation of safety training based in empowerment theory and its evaluation
      to address three levels in empowerment's hierarchy of change. Pictographic pre-
      and post-tests were used to assess knowledge level changes. Individual and large
      group interviews were conducted to address attitudes and behavior-level changes.
      Results indicate that day laborers learn and apply lessons from this type of
      safety training. Findings also offer insight into challenges that day laborers
      encounter when trying to work safely as well as ideas for future training
      interventions.

PMID- 22967372
TI  - Effect of normobaric hypoxia on the testis in a murine model.
AB  - High-altitude hypoxia generates spermiogram impairment due to germinal
      epithelium, Leydig cells, sperm and seminal plasma alterations, but precise
      mechanisms involved are unknown. The objective of this work was to analyse the
      effect of normobaric hypoxia on the morphology of testicular interstitium and
      some associated molecular and hormonal factors. Twenty-four mice were exposed to
      normobaric hypoxia (8.1% inspired oxygen fraction) during 20 days. The effects on
      body weight, testicular weight, vascularisation, testosterone, HIF1-alpha and
      VEGF were analysed at different periods of exposure and compared to controls.
      Hypoxic mice had lower body weight than mice kept in normoxia. Testicular weight
      raised significantly the 1st day, but remained normal during the rest of
      experiment. Number of blood vessels per field and mean diameter of vessels were
      higher in hypoxic mice. Plasmatic and testicular testosterone raised during first
      24 h of hypoxia, but decreased on the 5th day. Vascular/interstitial ratio
      (proportion of interstice occupied by blood vessels) duplicated at the end of the
      experiment. Most substantial early effects of hypoxia were testicular oedema,
      increase in number and diameter of blood vessels and elevation of plasmatic and
      testicular testosterone. Normobaric hypoxia generates similar effects to those
      induced by hypobaric hypoxia.

PMID- 22967373
TI  - Development of ecotoxicity QSAR models based on partial charge descriptors for
      acrylate and related compounds.
AB  - Using Gasteiger's partial equalization of orbital electronegativity (PEOE)
      method, we constructed ecotoxicity prediction equations based on two-dimensional
      descriptors for alpha,beta-unsaturated carbonyl compounds. After examining
      electrostatic effects on the calculated ecotoxicities of 10 alpha,beta
      unsaturated ketones and aldehydes (A-group compounds) by using the Mulliken
      atomic charges on the carbonyl oxygen atoms, we investigated the efficacy of the
      PEOE descriptors for the same 10 compounds and the correlation between the PEOE
      descriptors and the Mulliken charge. We then constructed QSAR models for acute
      fish and Daphnia toxicities by using the PEOE descriptors for acrylic acids and
      compounds with acrylate-like substructures (CH-group compounds). In the
      constructed models, the adjusted squared correlation coefficients between
      measured and calculated toxicities with the lowest Akaike information criterion
      were 0.77 and 0.79, respectively. The applicability of the constructed models was
      then evaluated for various methacrylates and similar compounds (CH(3)-group
      compounds). Both the fish and the Daphnia toxicities of some of the CH(3)-group
      compounds were underestimated by these models. Nevertheless, we concluded that
      the QSAR models based on the PEOE descriptors were practical for predicting acute
      toxicity, especially for alpha,beta-unsaturated carbonyl compounds with an alpha
      hydrogen. Combining hydrophobicity and PEOE descriptors led to accurate
      predictions for fish toxicity.

PMID- 22967374
TI  - [Establishment of human homoharringtonine-resistant SKM-1 cell line and its
      biological characteristics].
AB  - OBJECTIVE: To establish a homoharringtonine (HHT)-resistant SKM-1 cell line and
      explore its biologic characteristics and mechanisms for drug resistance. METHODS:
      The HHT-resistant SKM-1 cell line was established by repeatedly exposing the
      cells to comparatively large doses of HHT with a short-time duration, and
      gradually elevating the drug concentration to an endurable level. The morphology
      of the resistant and parental cell lines was observed through optical microscope.
      The MTT assay was used to determine the doubling time and the resistance index to
      draw growth curve. The immunophenotype, cell cycle distribution and DNR
      accumulation between SKM-1 and SKM-1/HHT were analyzed by flow cytometry, and the
      karyotypes by R-banding. Semi-quantitative real-time PCR was performed to
      evaluate the expression levels of mdr1, MRP and topo-IIa. RESULTS: The HHT
      resistant cell line SKM-1/HHT was eventually established following 7-month drug
      induction. Both the resistant and the parental cell lines were similar with
      regard to morphology and immunophenotype. The karyotypes of the former was more
      complicated with differences located in chromosome 20, X, 4, 5, 9 and 11. The
      resistant cell line had more G(1) phase cells (64.04% vs 41.91%), less S phase
      cells (34.92% vs 53.53%), and less G(2) phase cells (1.04% vs 4.56%) compared
      with the parental cell line. The SKM-1/HHT cell line showed significant drug
      resistance to HHT, VCR, DNR and etoposide, the resistance indices of HHT, VCR,
      DNR and etoposide were 17.94, 8.75, 5.99 and 13.76 respectively. DNR accumulation
      was impaired in SKM-1/HHT cell line as less fluorescence of DNR (698 +/- 36 vs
      858 +/- 54). The expression of mdr1 increased dramatically in the resistant cell
      line, its 2(-DeltaCt) value was 20.1 higher than that of the parental cell line
      ?[(3.42 +/- 0.46)*10(-2) vs (0.17 +/- 0.01)*10(-2), P < 0.05?], while MRP also
      increased in the resistant by 3.56 folds ?[(4.77 +/- 0.87)*10(-3) vs (1.34 +/-
      0.56)*10(-3), P < 0.05?]; However there was a slightly decrease of topo-IIa, the
      ratio of the resistant to the parental calculated by their 2(-DeltaCt) values was
      0.619:1 ?[(1.91 +/- 0.30)*10(-4) vs (3.08 +/- 0.21)*10(-4), P < 0.05?].
      CONCLUSION: A HHT-resistant cell line SKM-1/HHT was established. The prominent
      overexpression of mdr1 may be the main cause for multidrug resistance.

PMID- 22967375
TI  - [Anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia cell SUP
      B15].
AB  - OBJECTIVE: To investigate the anti-leukemia effect of oridonin on Ph(+) acute
      lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: Human Ph(+) ALL cell
      line was cultured in vitro. The 50% inhibition concentration (IC(50)) of oridonin
      against SUP-B15 cell line was examined using modified MTT assay. The cellular
      morphologic changes were observed using a light microscope. The percent of
      apoptosis of SUP-B15 cell line after drug treatment was evaluated by flow
      cytometric analysis. The active levels of ABL kinase and its downstream Akt/mTOR,
      Raf/MEK/ERK, STAT5 signaling pathways and the expression levels of Bcl-2 and BAX
      were examined by Western blot. RESULTS: Oridonin inhibited the growth of SUP-B15
      cell line in both time- and dose-dependent manner with the IC(50) of oridonin as
      (7.08 +/- 1.21) umol/L after 72 h treatment. The cellular membrane of SUP-B15
      cell line treated with oridonin became unsharp, some of them disintegrated.
      Oridonin induced apoptosis in SUP-B15 cell line with the apoptosis rates
      following 0, 5, 10 umol/L oridonin treatment for 24 h were (6.67 +/- 0.83)%,
      (18.30 +/- 1.79)% and (37.63 +/- 7.12)%, respectively. Oridonin inhibited
      activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5
      signaling pathways, which were constitutively activated in SUP-B15 cell line,
      down-regulated the level of anti- apoptotic protein Bcl-2 and up-regulated the
      expression of pro-apoptotic protein Bax. CONCLUSION: Oridonin exerted anti
      leukemia effect in Ph(+)ALL cell line SUP-B15 by inhibiting the activation of ABL
      kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways,
      down-regulating the expression of Bcl-2 and up-regulating the expression of BAX.

PMID- 22967376
TI  - [A case of myasthenia gravis combined with acquired hemophilia A].

PMID- 22967377
TI  - [NKG2D-mediated natural killer cell cytotoxicity against myeloid leukemia cells
      OUN-1].
AB  - OBJECTIVE: To investigate NK cell cytotoxicity to leukemic cell by NKG2D
      receptors and NKG2D ligands interaction upregulated by hydroxyurea (HU). METHODS:
      Leukemic cell lines OUN-1 and primary leukemic cells were cultured for 24 hours
      in the presence of HU, then the NKG2D ligands expressions were analyzed by flow
      cytometry (FCM). Isolated NK cells from healthy individual cultured for 72 hours
      in presence of IL-2 were used as effect cell, and leukemic cell line OUN-1
      treated with HU was used as target cell, NK cell cytotoxicity against leukemic
      cell line was assessed using chromium-51 release assay. RESULTS: Leukemic cell
      lines showed upregulation of MIC A/B (MFI: 8.9 +/- 0.9 vs 23.5 +/- 3.4, P = 0.01)
      and ULBP2 (MFI: 14.5 +/- 0.6 vs 33.5 +/- 4.8, P = 0.03) following incubation with
      HU. HU also upregulated the NKG2DLs on primary leukemia cells from patients with
      acute myeloid leukemia. Treatment of OUN-1 with HU significantly increased the
      cytotoxicity of NK cells isolated from healthy individual ?[(62.0 +/- 5.6)% vs
      (76.0 +/- 5.3)%, P = 0.02?], and the enhancing effect of HU was partly blocked by
      anti-NKG2D Abs ?[(76.0 +/- 5.3)% vs (46.0 +/- 4.5)%, P = 0.00?]. CONCLUSION: HU
      selectively upregulated NKG2D ligand expression on leukemic cell lines, and
      enhanced NK cell cytotoxicity against leukemic cells through NKG2D receptors and
      NKG2D ligands interaction.

PMID- 22967378
TI  - [The effects of lentivirus-mediated RNA interference silencing HMGA2 on
      proliferation and expressions of cyclin B2 and cyclin A2 in HL-60 cells].
AB  - OBJECTIVE: To explore the effects of lentivirus-mediated RNA interference
      silencing HMGA2 on proliferation and expressions of cyclin B2 and cyclin A2 in HL
      60 cell line. METHODS: The protein and mRNA expressions of HMGA2 in HL-60 cells
      transduced by recombinant lentivirus producing HMGA2 gene short hairpin (shRNA)
      were examined by Western-blot and reverse transcription-polymerase chain reaction
      (RT-PCR) analysis; The effects of the lentivirus on cell proliferation inhibiting
      rate, the ability of cell proliferation and cell cycle were analyzed by soft agar
      colony formation assay and FCM, respectively; The protein and mRNA expressions of
      cyclin B2 and cyclin A2 were also examined by Western-blot and RT-PCR. RESULTS:
      Recombinant lentivirus producing HMGA2 shRNA was successfully constructed, which
      was identified by PCR and sequencing; Stable HMGA2-deficient HL-60 cell line was
      established by puromycin, its mRNA and protein expression inhibition rates were
      (80.66 +/- 7.98)% and (76.35 +/- 12.72)%, respectively. Silencing of endogenous
      HMGA2 resulted in efficient inhibition of the cellular proliferative activity,
      low and flat of the cell growth curve and the lack of typical character of
      exponential growth. FCM revealed significant more cell cycle G(2)/M arrest
      ?[(30.00 +/- 5.78)%?] in HL-60 cell line transfected specific shRNA than control
      group ?[(13.90 +/- 4.07)%?] (P < 0.05). The cyclin B2 mRNA and protein expression
      inhibition rates in stable HMGA2-deficient HL-60 cell line were (67.55 +/- 7.69)%
      and (51.77 +/- 4.81)%, respectively, while the expression of cyclin A2 had no
      significant change compared with control group. CONCLUSION: RNAi silencing of
      HMGA2 down-regulated cyclinB2, significantly inhibited the proliferation of HL-60
      cells and induced the accumulation of HL-60 cells in the G(2)/M phase. Thus,
      HMGA2 may be an important target for anti-leukemia therapy.

PMID- 22967379
TI  - [The effect of knockdown of transcription factor SCL/TAL-1 gene on the erythroid
      differentiation in EPO-induced K562 cell line].
AB  - OBJECTIVE: To investigate the role of transcript factor SCL/TAL-1 gene in the
      erythroid differentiation through the knockdown of SCL/TAL-1 mRNA by RNA
      interference. METHODS: The plasmid of pTRIP-dU3-RNAiTALh-EF1a-GFP with SCL/TAL1
      shRNA was transfected into EPO-induced K562 cell line with erythroid
      differentiation via lentiviral vector system and the expression of SCL/TAL-1 mRNA
      decreased. The plasmid pTRIP-dU3- RNAiluc-EF1-GFP expressing EGFP gene was as
      control. The mRNA levels of SCL/TAL-1 and erythroid related RhD, GPA, CD47 in the
      cell lines were detected by RT-PCR, and erythroid antigen CD71, CD235a were
      examined by flow cytometry. RESULTS: (1) After 48 h of transfect, more than 95%
      of K562 cells were GFP positive, indicating the infection rate of the plasmids in
      the K562 cells more than 95%. (2) The results of RT-PCR showed SCL/TAL-1 mRNA
      expression in the K562 cell line of knockdown of SCL/TAL-1 was significantly
      lower than that in the control (P < 0.05). The mRNA levels of CD47 and RhD were
      also significantly lower, however, GPA decreased slightly in comparison with the
      control. (3) The expressions of CD71 and CD235a markedly reduced in the K562 cell
      line of knockdown of SCL/TAL-1 with positive rates as 10.4% and 76.5%, while the
      positive rates in the control as 94.3% and 83.6%. CONCLUSION: Our findings
      suggested that transcription factor SCL/TAL-1 might play an positive role in
      erythroid differentiation.

PMID- 22967380
TI  - [Anti-angiogenesis effect of metronomic chemotherapy in multiple myeloma
      patients].
AB  - OBJECTIVE: To investigate effects of low-dose cyclophosphamide and prednisone
      (CP) metronomic chemotherapy on microvessel density of bone marrow, serum
      vascular endothelial growth factor (VEGF) and platelet derived growth factor BB
      (PDGF-BB)in multiple myeloma (MM) patients. METHODS: 54 refractory or relapsed MM
      patients were treated with CP metronomic chemotherapy consisted of oral
      cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and
      peripheral blood of each patient were collected before and 2, 4, 6 months after
      treatment. Among the 37 assessable patients, 30 cases were responsive with the
      response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or
      failure to obtain serum samples or lost to follow-up. Microvessel density of bone
      marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was
      analyzed by ELISA in the 37 assessable patients. RESULTS: 2, 4, 6 months
      following CP metronomic chemotherapy, microvessel densities of bone marrow in the
      responders were 33.1 +/- 4.8/HP, 24.8 +/- 3.7/HP, 19.7 +/- 2.1/HP respectively;
      the expressions of VEGF were (394 +/- 57) ng/L, (268 +/- 32) ng/L and (217 +/-
      20) ng/L respectively; the expressions of PDGF-BB were (304 +/- 31) ng/L, (274 +/
      31) ng/L and (196 +/- 22) ng/L respectively. After CP metronomic chemotherapy,
      there were significantly lower of microvessel density, VEGF and PDGF-BB levels
      than pretreatment ?[MVD 48.5 +/- 5.9/HP, VEGF (517 +/- 60) ng/L, PDGF-BB (484 +/-
      60) ng/L?]in the responders (P < 0.01). While in the non-responders, after
      treated by CP metronomic chemotherapy for 2 months, microvessel density, the
      expression of VEGF and the expression of PDGF-BB were 32.5 +/- 4.7/HP, 512 +/- 39
      ng/L and (452 +/- 39) ng/L respectively. There were no significant changes of
      MVD, VEGF and PDGF-BB levels compared with pretreatment ?[MVD 33.2 +/-
      5.6/HP,VEGF (498 +/- 55) ng/L, PDGF-BB (488 +/- 44) ng/L?] (P > 0.05).
      CONCLUSIONS: Our findings suggested that continuous low-dose CP metronomic
      chemotherapy could decrease microvessel density of bone marrow in MM patients.
      Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its
      anti-angiogenesis in MM.

PMID- 22967381
TI  - [The role of third-party tolerogenic dendritic cells in the prevention of acute
      graft-versus-host-disease following allogeneic bone marrow transplantation in
      mice].
AB  - OBJECTIVE: To explore the biological characteristic of third-party-derived
      tolerogenic DC(tDC) and the influence of third-party-derived tDC on acute graft
      versus-host-disease (aGVHD) following allogeneic bone marrow transplantation
      (allo-BMT) in mice. METHODS: tDC from bone marrow cells of D1 mice was cultured
      with low doses of GM-CSF, IL-10 and TGF-beta1D1. The phenotype, expression of
      cytokines and function associated molecules were identified with FACS and RT-PCR.
      Mixed lymphocyte reaction was applied to analyze the influence of third-party
      derived tDC on allo-CD4(+)T cells proliferation in vitro. Different doses of D1
      tDC were adoptive transferred in the aGVHD model in allogeneic BMT which B6 mice
      as donors and D2 mice as recipients. Survival time, clinical GVHD score and the
      levels of Th1/2 cytokines in serum were monitored after allo-BMT using the aGVHD
      model as control. RESULTS: tDC expressed lower levels of MHC II and co
      stimulatory molecules, such as CD80, CD86 and CD40, even when stimulated by LPS.
      The results by RT-PCR indicated that tDC expressed low levels of IL-12p40 and
      high levels of immunosuppressive molecules, such as IL-10, TGF-beta, Fas Ligand,
      indoleamine 2, 3-dioxygenase (IDO) and arginase. In the allogeneic MLR, third
      party tDC suppressed allo-CD4(+)T cells proliferation, which was relative to the
      dose of tDC. In the B6->D2 mouse model, all aGVHD mice died within 18 days.
      Remarkably, if 10(4) third-party tDC were transferred, 60% mice survived at least
      60 days. When the doses of tDC were reduced to 10(3) cells, only 20% of mice
      survived day 60, and when increased tDC to 10(5), all of the mice died within day
      37 after allo-BMT. The cytokine levels in serum indicated that 10(4) tDC-treated
      mice secreted in vivo high level of IL-10 21d after BMT (P < 0.05), the levels of
      IL-10 in 10(3), 10(4) and 10(5) tDC-treated mice were (114.23 +/- 7.78), (646.18
      +/- 212.02), (121.97 +/- 10.47) ng/L, respectively. CONCLUSION: Third-party tDC
      could suppress allo-CD4(+)T cells proliferation in vitro and prevent aGVHD in
      allogeneic BMT mode, which may be mediated by modulating tolerogenic cytokines
      secretion, such as IL-10. And this effect was associated with the dose of tDC.
      Adoptive therapy by transfusing third-party tDC cultured with low doses of GM
      CSF, IL-10 and TGF-beta1 could significantly prolong the survival of recipients
      and prevent aGVHD in allogeneic BMT.

PMID- 22967382
TI  - [Salvaged allogeneic hematopoietic stem cell transplantation for
      refractory/recurrent acute myeloid leukemia].
AB  - OBJECTIVE: To evaluate the efficacy of salvaged allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) for refractory/recurrent acute myeloid leukemia
      (AML). METHODS: A total of 45 patients with refractory/recurrent AML were
      enrolled from September 2006 to April 2010. The median blasts in bone marrow (BM)
      were 36% (20% to 92%) before conditioning. The donors were identical siblings (6)
      or unrelated ones (9) or haploidentical family members (30). Conditioning
      regiments were individualized according to patients' status, the regimen with
      high-dose cytarabine plus BuCy/CY was mostly used (20). The patients with
      impaired organ function received above regimen except using fludarabine instead
      of cyclophosphamide (16). FLAG followed by reduced-intensified BuCy was employed
      for the recipients with more than 40% blasts in BM (6) to reduce leukemia burden.
      TBI/CY or TBI/Fludarabine was used for the recipients with extramedullary
      infiltration of leukemia or multidrug resistant leukemia. G-CSF, MTX, NVT, Vm26,
      Acla or Thaltipa was added into conditioning regiments according to leukemia
      character. RESULTS: All but 2 patients attained durable engraftment. The
      incidence of grade II to IV aGVHD and cGVHD were 34%, 59.1%, respectively. With
      median follow-up 30 (0.5 - 57) months, the relapse rate was 29.2%. Twenty-nine of
      45 (60.2%) patients remained in complete remission since salvaged HSCT. Three
      years disease-free survival and overall survival were 60.2% and 62.6%,
      respectively. CONCLUSION: Our results indicated that the combination of salvaged
      HSCT with prophylactic immunotherapy might be a promising modality for treatment
      of refractory/recurrent AML, even with high leukemia burden.

PMID- 22967383
TI  - [Clinical features of 76 Chinese patients with paroxysmal nocturnal
      haemoglobinuria].
AB  - OBJECTIVE: To further analyse the relationship between the new technology and
      clinical characteristics in paroxysmal nocturnal haemoglobinuria (PNH) patients,
      and summarize the data of PNH during the past 15 years in China. METHODS: 76
      consecutive patients with PNH diagnosed in Peking Union Medical Colleague
      Hospital from 1997 - 2011 retrospectively. RESULTS: Most of the patients were
      diagnosed based on flow cytometric data. There were 46 male and 30 female
      patients. The median age at diagnosis was 40 (10 - 74). 46 (60.5%) patients
      presented with classical PNH, 16 (21.1%) pancytopenia, and 14 (18.4%) thrombosis.
      Anatomic locations of first thrombosis were intra abdominal in 7 patients, lower
      extremities in 3 patients, intracerebral in 2 patients, and pulmonary thrombosis
      in 2 patients. The size of PNH clone at first determination (shown by CD55 and
      CD59 negative percentage) was (61.23 +/- 27.47)% and (60.24 +/- 25.59)% on
      neutrophils; (34.24 +/- 25.50)% and (32.22 +/- 23.12)% on erythrocytes,
      respectively. The mean LDH level was (1199.2 +/- 893.5) U/L. In our cohort,
      13(17.0%) patients suffered from renal deficiency, 12 (15.8%) patients
      cholecystolithiasis, 10 (13.2%) patients hemorrhage and 9 (11.8%) patients
      infections. In a median of 7-year (range 0.5 - 20 years) follow-up (68 patients),
      2 (2.9%) patients developed into myelodysplastic syndromes/ acute myeloid
      leukemia, 1(1.5%) patient ovary cancer, 11(14.5%) patients died. Patients with
      thrombosis had higher percentage of CD59 negative neutrophils ?[(73.45 +/-
      22.32)%?] compared with those without thrombosis ?[(58.3 +/- 20.2)%?] (P < 0.05).
      CONCLUSIONS: The cohort had higher percentage of classical hemolysis, thrombosis
      and renal dysfunction compared with previous reports in China. Patients with
      thrombotic events had higher percentages of CD55 and CD59 negative neutrophils.

PMID- 22967384
TI  - [A case of non-Hodgkin lymphoma combined with primary renal cell carcinoma].

PMID- 22967385
TI  - [Genotype and function analyses of four inherited dysfibrinogenemia pedigree
      caused by Arg16 amino acid substitution in fibrinogen Aalpha chain].
AB  - OBJECTIVE: To analyze the phenotype, genotype and function in four Chinese
      pedigrees with inherited dysfibrinogenemia. METHODS: Routing tests including
      activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin
      time (TT), reptilase time (RT), the activities of antithrombin (AT), protein C
      (PC) and protein S (PS) were detected in four pedigrees. The activity and antigen
      of plasma fibrinogen were analyzed by Clauss and immunoturbidimetry methods,
      respectively. The molecular weight of fibrinogen of four probands was assessed by
      Western blot. The function of abnormal fibrinogen was evaluated by fibrinogen
      clottability, fibrinogen dynamic polymerization and fibrinolysis velocity,
      respectively. The sequences of all the exons and exon-intron boundaries of the
      three fibrinogen genes were amplified by PCR and analyzed by direct sequencing.
      RESULTS: Four probands had prolonged TT and RT, reduced plasma fibrinogen
      activity levels and normal antigen levels. The assays of Western blot showed no
      abnormal molecular weight of fibrinogen. Function tests revealed reduced
      fibrinogen clottability, delayed and decreased fibrinogen dynamic polymerization
      and reduced fibrinolysis velocity. Aalpha chain Arg16His and Arg16Cys mutations
      were identified in the four probands, respectively. CONCLUSION: The four probands
      with dysfibrinogenemia were caused by the mutations of Aalpha chain Arg16His or
      Arg16Cys. Mutation of the fibrinogen induced dysfunction of plasma fibrinogen.

PMID- 22967386
TI  - [STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the
      patients with myelodysplastic syndrome].
AB  - OBJECTIVE: To investigate the expressions of STAT5 phosphorylation in
      CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic
      syndromes (MDS), and then evaluate the level of activation of STAT5 associated
      with cell proliferation in MDS clone cells. METHODS: The bone marrow mononuclear
      cells (BMMNC) were extracted from 36 MDS patients and 14 normal controls. The
      mean fluorescence intensities (MFI) of phosphorylated STAT5(P-STAT5) in
      CD34(+)CD38(-)CD123(+) and CD34(+)CD38(-)CD123(-)cells, with or without the
      stimulation of 10 U/ml EPO, were examined by flow cytometry (FCM). RESULTS:
      Without stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high
      risk MDS patients was 113.71 +/- 67.22/173.05 +/- 102.78, which was significantly
      higher than that of CD34(+)CD38(-)CD123(-) cells (58.84 +/- 27.51/68.99 +/-
      50.42, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells
      (63.06 +/- 21.06, P < 0.05), there was no significant difference between the
      CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(
      )CD123(-) cells; With the EPO stimulation, the P-STAT5 MFI in CD34(+)CD38(
      )CD123(+) cells of low/high risk MDS patients was 144.04 +/- 58.11/239.45 +/-
      152.05, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells
      (68.41 +/- 25, 10/64.21 +/- 23.43, P < 0.01) and the normal controls CD34(+)CD38(
      )CD123(-) cells (75.21 +/- 27.02, P < 0.01), there was no significant difference
      between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control
      CD34(+)CD38(-)CD123(-) cells; The P-STAT5 MFI in the CD34(+)CD38(-)CD123(+) cells
      of low/high risk MDS patients with or without EPO stimulation were 21.80/28.86,
      which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells
      (7.42/5.50, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-)
      cells (6.39, P < 0.05), there was no significant difference between the
      CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal controls CD34(+)CD38(
      )CD123(-) cells; There was no significant difference of P-STAT5 MFI with or
      without EPO stimulation and the increased P-STAT5 MFI between the CD34(+)CD38(
      )CD123(+) cells of low and high risk MDS. CONCLUSION: STAT5 associated with cell
      proliferation was activated in CD34(+)CD38(-)CD123(+) bone marrow cells in MDS,
      which had more significant reactions to EPO than CD34(+)CD38(-)CD123(-) cells,
      indicating that CD34(+)CD38(-)CD123(+) bone marrow cells might be the real
      malignant MDS clone cells in MDS.

PMID- 22967387
TI  - [Comparative evaluation of CHAG and CAG priming regimen for treatment of
      refractory and relapsed acute myeloid leukemia].

PMID- 22967388
TI  - [Effect of proliferation inhibition and PTEN gene expression induced by
      decitabine combined with daunorubicin on HL-60 cell line].

PMID- 22967389
TI  - [Study on the proapoptotic effect of human par-4 gene in K562 cells].

PMID- 22967390
TI  - [Effect of splenectomy on thrombocytopenia in a case of thrombotic
      microangiopathy after stem cell transplantation].

PMID- 22967391
TI  - [Hydroa vacciniforme-like cutaneous T cell lymphoma: two cases report and
      literature review].

PMID- 22967392
TI  - [Evaluation of nutritional status and the time of engraftment in patients
      undergoing hematopoietic stem cell transplantation].

PMID- 22967393
TI  - [Clinical application of bleeding scoring system in immune thrombocytopenia].

PMID- 22967394
TI  - [Advances in grey platelet syndrome].

PMID- 22967395
TI  - Exuberant accessory mitral valve tissue with possible true parachute mitral
      valve: a case report.
AB  - INTRODUCTION: A parachute mitral valve is defined as a unifocal attachment of
      mitral valve chordae tendineae independent of the number of papillary muscles.
      Data from the literature suggests that the valve can be distinguished on the
      basis of morphological features as either a parachute-like asymmetrical mitral
      valve or a true parachute mitral valve. A parachute-like asymmetrical mitral
      valve has two papillary muscles; one is elongated and located higher in the left
      ventricle. A true parachute mitral valve has a single papillary muscle that
      receives all chordae, as was present in our patient. Patients with parachute
      mitral valves during childhood have multilevel left-side heart obstructions, with
      poor outcomes without operative treatment. The finding of a parachute mitral
      valve in an adult patient is extremely rare, especially as an isolated lesion. In
      adults, the unifocal attachment of the chordae results in a slightly restricted
      valve opening and, more frequently, valvular regurgitation. CASE PRESENTATION: A
      40-year-old Caucasian female patient was admitted to a primary care physician due
      to her recent symptoms of heart palpitation and chest discomfort on effort.
      Transthoracic echocardiography showed chordae tendineae which were elongated and
      formed an unusual net shape penetrating into left ventricle cavity. The
      parasternal short axis view of her left ventricle showed a single papillary
      muscle positioned on one side in the posteromedial commissure receiving all
      chordae. Her mitral valve orifice was slightly eccentric and the chordae were
      converting into a single papillary muscle. Mitral regurgitation was present and
      it was graded as moderate to severe. Her left atrium was enlarged. There were no
      signs of mitral stenosis or a subvalvular ring. She did not have a bicuspid
      aortic valve or coarctation of the ascending aorta. The dimensions and systolic
      function of her left ventricle were normal. Our patient had a normal body
      habitus, without signs of heart failure. Her functional status was graded as
      class I according to the New York Heart Association grading. CONCLUSIONS: A
      recently published review found that, in the last several decades, there have
      been only nine adult patients with parachute mitral valve disease reported, of
      which five had the same morphological characteristics as our patient. This case
      presentation should encourage doctors, especially those involved in
      echocardiography, to contribute their own experience, knowledge and research in
      parachute mitral valve disease to enrich statistical and epidemiologic databases
      and aid clinicians in getting acquainted with this rare disease.

PMID- 22967397
TI  - Homochiral helical metal-organic frameworks of potassium.
AB  - Two trifunctional ligands built from enantiopure amino acids and containing a 1,8
      naphthalimide group have been used to prepare two new complexes of potassium that
      have extended structures based on homochiral-rod secondary building units. One
      structure is a three-dimensional metal-organic framework (MOF), while the other
      is a two-dimensional solid that is organized into a supramolecular MOF by strong
      pi...pi-stacking interactions of the naphthalimide groups in the third dimension.

PMID- 22967396
TI  - Oncogenic human papillomavirus genital infection in southern Iranian women:
      population-based study versus clinic-based data.
AB  - BACKGROUND: Epidemiological studies on genital human papilloma viruses infection
      (HPVs) in general population are crucial for the implementation of health policy
      guidelines for developing the strategies to prevent the primary and secondary
      cervical cancer. In different parts of Iran, there is a lack of population-based
      studies to determine the prevalence of HPV in the general population. The aim of
      this population-based study is to compare the prevalence rate of genital HPV
      infection among reproductive women with our previous clinic-based data, which
      showed a prevalence rate of 5% in women in southern Iran. RESULTS: Using general
      primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%,
      95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV
      genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic,
      or "high risk genotypes" and one genotype (HPV-66) was "probably carcinogenic."
      CONCLUSIONS: In a population-based study, the prevalence of HPV infection among
      southern Iranian women was lower than that observed worldwide. However, our
      gynaecological clinic-based study on the prevalence of HPV infection showed
      results comparable with other studies in the Middle East and Persian Gulf
      countries. Since gynaecological clinic-based data may generally overestimate HPV
      prevalence, estimates of prevalence according to clinic-based data should be
      adjusted downward by the population-based survey estimates.

PMID- 22967399
TI  - Estradiol supplementation in intracytoplasmic sperm injection cycles with thin
      endometrium.
AB  - OBJECTIVE: To evaluate the efficacy of estradiol supplementation starting on the
      day of human chorionic gonadotrophin (hCG) in patients with thin endometrium in
      intracytoplasmic sperm injection (ICSI) cycles. METHODS: A total of 117
      consecutive patients with the endometrial thickness on the hCG day <= 8 mm were
      reviewed. Estradiol supplementation was given in 57 patients and the remaining 60
      patients were accepted as control group. Estradiol supplemented (ES) group
      received estradiol hemihydrate 4 mg/day started on the day of hCG. Luteal phase
      was supported using the vaginal progesterone gel in both groups. Clinical
      pregnancy rate, implantation rate, miscarriage rate, endometrial thickness on the
      day of oocyte pick-up and on the day of embryo transferred were accepted as main
      outcome measures. RESULTS: There were no statistical differences in terms of
      clinical pregnancy rate (28.1% vs. 23.3%), implantation rate (16% vs. 10.4%),
      miscarriage rate (21% vs. 31.6%), endometrial thickness on the oocyte pick-up day
      (8.5 +/- 1.8 vs. 8.4 +/- 1.4, mm) and embryo transferred day (9.6 +/- 2.9 vs.
      10.3 +/- 2.4, mm) in the ES group vs. control group. CONCLUSION: Estradiol
      supplementation starting on the hCG day for the patients with thin endometrium
      does not provide any benefit on the pregnancy outcome in ICSI cycles.

PMID- 22967400
TI  - [Further improvement of diagnosis and treatment of patients with myelodysplastic
      syndromes in China].

PMID- 22967401
TI  - [Systemic light chain amyloidosis with acquired factor X deficiency: a case
      report].

PMID- 22967398
TI  - Matrilin-3 induction of IL-1 receptor antagonist is required for up-regulating
      collagen II and aggrecan and down-regulating ADAMTS-5 gene expression.
AB  - INTRODUCTION: Deletion or mutation of the gene encoding the cartilage
      extracellular matrix (ECM) protein matrilin-3 (MATN3) results in the early onset
      of osteoarthritis (OA), suggesting chondroprotective properties of MATN3. To
      understand the mechanisms underlying these properties, we determined the effects
      of MATN3 protein on the expression of several key anabolic and catabolic genes
      involved in chondrocyte homeostasis, and the dependence of such regulation on the
      anti-inflammatory cytokine: IL-1 receptor antagonist (IL-1Ra). METHODS: The
      effects of recombinant human (rh) MATN3 protein were examined in C28/I2
      immortalized human chondrocytes, primary human chondrocytes (PHCs), and primary
      mouse chondrocytes (PMCs). Messenger RNA levels of IL-1Ra, COL2A1, ACAN, MMP-13,
      and ADAMTS-4 and -5 were determined using real-time RT-PCR. Knocking down IL-1Ra
      was achieved by siRNA gene silencing. IL-1Ra protein levels were quantified by
      ELISA and the Bio-Plex Suspension Array System. COL2A1 protein level was
      quantified using Western blot analysis. Statistic analysis was done using the two
      tailed t-test or one-way ANOVA. RESULTS: rhMATN3 protein induced gene expression
      of IL-1Ra in C28/I2 cells, PHCs, and PMCs in a dose- and time-dependent manner.
      Treatment of C28/I2 cells and PHCs with MATN3 protein stimulated gene expression
      of COL2A1 and ACAN. Conversely, mRNA levels of COL2A1 and ACAN were decreased in
      MATN3 KO mice. MATN3 protein treatment inhibited IL-1beta-induced MMP-13, ADAMTS
      4 and ADAMTS-5 in C28/I2 cells and PHCs. Knocking down IL-1Ra abolished the MATN3
      mediated stimulation of COL2A1 and ACAN and inhibition of ADAMTS-5, but had no
      effect on MATN3 inhibition of MMP-13 mRNA. CONCLUSION: Our findings point to a
      novel regulatory role of MATN3 in cartilage homeostasis due to its capacity to
      induce IL-1Ra, to upregulate gene expression of the major cartilage matrix
      components, and to downregulate the expression of OA-associated matrix-degrading
      proteinases in chondrocytes. The chondroprotective properties of endogenous MATN3
      depend partly on its induction of IL-1Ra. Our findings raise a possibility to use
      rhMATN3 protein for anti-inflammatory and chondroprotective therapy.

PMID- 22967403
TI  - [Management options of patients with intermediate and high risk myelodysplastic
      syndromes].

PMID- 22967402
TI  - [Standards in the diagnosis and classification of myelodysplastic syndromes].

PMID- 22967404
TI  - [Management of patients with lower risk myelodysplastic syndromes].

PMID- 22967405
TI  - [Hematopoietic stem cell transplantation for myelodysplastic syndromes].

PMID- 22967406
TI  - [Prognosis prediction for myelodysplastic syndromes].

PMID- 22967407
TI  - [Basic studies for demethylating agent-based therapy in myelodysplastic
      syndromes].

PMID- 22967408
TI  - [Some clinical issues for epigenetic therapy in myelodysplastic syndromes].

PMID- 22967409
TI  - [Analysis of in vitro characteristics of colony-forming cells in myelodysplastic
      syndrome and comparison with that in non-severe aplastic anemia].
AB  - OBJECTIVE: To investigate in vitro characteristics of colony-forming cells (CFC)
      in patients with myelodysplastic syndrome (MDS) and to compare that in patients
      with non-severe aplastic anemia (NSAA). METHODS: Data of in vitro CFC and
      correlation with other related laboratory tests in 155 newly diagnosed MDS
      patients were analyzed retrospectively, and to compare with data of in vitro CFC
      in 122 newly diagnosed NSAA patients. RESULTS: Median number of burst-forming
      units-erythroid (BFU-E) was 9 (0 - 157)/10(5) bone marrow mononuclear cells
      (BMMNC), colony forming unit-erythroid (CFU-E) 30 (0 - 425)/10(5)BMMNC and colony
      forming unit-granulocytes/macrophages (CFU-GM) 14 (0 - 125)/10(5)BMMNC in
      patients with MDS, being significantly lower than those in healthy control;
      number of BFU-E and/or CFU-E was lower than the lower limit of normal control in
      66 cases (42.6%), CFU-GM lower in 3 cases (1.9%) and BFU-E and/or CFU-E with CFU
      GM lower in 70 cases (45.2%). Cluster/CFU-GM ratio was significantly lower in low
      blast group (MDS < 5% blast in bone marrow smear) than that in high blast group
      (MDS >= 5% blast) (0.65 vs 1.0, P = 0.049). In all MDS patients, cluster had
      positive correlation with each type of CFC (r = 0.415, 0.338, 0.642 for BFU-E,
      CFU-E, CFU-GM, respectively, P = 0.000), but had negative correlation with
      neutrophil alkaline phosphatase (N-ALP) positive rate and scores (r(rate) = 
      0.315, P = 0.001 and r(scores) = -0.257, P = 0.006). The median number of each
      type of CFC was significantly higher in MDS group than that in NSAA group (BFU-E
      9 vs 5/10(5)BMMNC, P = 0.017; CFU-E 30 vs 19.5/10(5)BMMNC, P = 0.023; CFU-GM 14
      vs 10/10(5)BMMNC, P = 0.003, respectively). Positive correlation between BFU-E
      and CFU-E were revealed in both MDS and NSAA group (r(MDS) = 0.712, P = 0.000 and
      r(NSAA) = 0.757, P = 0.000), with a lower correlation coefficient in MDS (P <
      0.05). CONCLUSIONS: Early onset MDS present markedly decreased hematopoietic
      progenitor cells (HPC), and particularly in erythroid progenitors extensively and
      severely. The number of BFU-E, CFU-E and CFU-GM can reflect HPC number in vivo
      but not stand for normal hematopoietic clones, the number of clusters represent
      pathologic HPC clones but not exactly leukemic blasts.

PMID- 22967410
TI  - [Significance of interplay between Rap1 and cadherin to the development of
      myelodysplastic syndrome].
AB  - OBJECTIVE: To explore the hematopoietic pathophysiology of myelodysplastic
      syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression
      profiles associated with hematopoiesis. METHODS: The differentially expressed
      genes which were involved in the hematopoiesis were screened by microarray using
      CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the
      screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype.
      The linkages with hematopoiesis among these validated genes were analyzed.
      RESULTS: Among the differentially expressed genes in CD34(+) cells of MDS-RA
      patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can
      interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated
      significantly (P < 0.01). beta-catenin, a downstream effector of cadherins, was
      highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down
      regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P <
      0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated
      with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA
      patients (P < 0.01). CONCLUSION: The abnormal expression of cadherin, beta
      catenin and c-myc associated genes were closely related to the dysplastic
      hematopoiesis of MDS. The down regulation of cadherin was associated with the
      positive feedback mechanism between Rap1 and cadherin. The aberrant expression of
      Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.

PMID- 22967411
TI  - [Clinical features and survival analysis in primary myelodysplastic syndromes
      patients with immunological abnormalities].
AB  - OBJECTIVE: To analyze the clinical features and survival time in primary
      myelodysplastic syndromes (MDS) patients accompanied with immunological
      abnormalities. METHODS: The clinical information, laboratory findings and
      survival time in 194 untreated primary MDS patients with complete immunological
      laboratory tests or a past history of autoimmune disease were analyzed
      retrospectively. RESULTS: There were 37/194 cases (19.07%) with autoimmune
      abnormalities, including 16/194 (8.25%) with autoimmune disease and 21/194
      asymptomatic cases (10.82%) with serologic immunological abnormalities only.
      There was significant differences in the distribution of age < 60 years old,
      female, CD4(+)T-cell/CD8(+)T-cell ration < 1 and trisomy 8 (P < 0.05) between the
      cases with autoimmune disease and without autoimmune abnormalities. The former
      had a higher 2-year OS, but there was no significance (P = 0.065). There was no
      significant differences in the distribution of age, MDS-subtype, IPSS risk
      groups, haemoglobin, absolute neutrophil count, platelets count, the severity of
      anemia and neutropenia, high level of serologic TNF, chromosomal abnormalities,
      cytogenetic risk groups and bone marrow cellularity (P > 0.05). CONCLUSION: MDS
      patients with autoimmune disease are mainly female and younger than 60 years old,
      with high proportion of trisomy 8 and better prognosis.

PMID- 22967412
TI  - [A preliminary study of prognostic value of thrombocytopenia in patients with
      primary myelodysplastic syndromes].
AB  - OBJECTIVE: To investigate the prognostic value of thrombocytopenia in patients
      with primary myelodysplastic syndromes (MDS). METHODS: Four hundred and nineteen
      primary MDS patients were retrospectively analyzed. Kaplan-Meier method, Log-rank
      test and COX regression model were used to evaluate factors that influence the
      prognosis. RESULTS: Two hundred and fifty-six cases (61.1%) had thrombocytopenia
      (PLT < 100*10(9)/L), one hundred and three cases (24.6%) had severe
      thrombocytopenia (PLT < 30*10(9)/L). Overall survival (OS) tended to shorten
      along with the decreasing of platelet count. Univariate analysis indicated that
      PL < 30*10(9)/L, MCV <= 95 fl, LDH >= 300 U/L, lymphocyte-like
      micromegakaryocyte, nucleated RBC PAS positive, IPSS cytogenetic intermediate-
      and poor-risk were all related with poor prognosis. Moreover, the prognosis of
      patients with RCMD, RAEB-Ior RAEB-IIwas poorer than that of the other subgroups.
      Among these parameters, PLT < 30*10(9)/L, MCV <= 95 fl, IPSS cytogenetic
      intermediate- and poor-risk group and RCMD, RAEB-I and RAEB-II had independent
      prognostic significance in multivariate analysis. Modified WPSS prognostic model
      was proposed by adopting PLT, MCV, chromosomal karyotype and WHO classification.
      The OS of patients with low risk, intermediate-1 risk, intermediate-2 risk and
      high risk were 59, 28, 14 and 4 months, respectively, and there was a
      statistically significant difference between the groups (P < 0.05). CONCLUSION:
      Severe thrombocytopenia indicated unfavorable prognosis, in combination with MCV,
      chromosomal karyotype and WHO classification, a modified WPSS prognostic model
      was proposed and worked well for prognostic indication in patients with MDS.

PMID- 22967413
TI  - [Clinical significance of the Wilms' tumor 1 mRNA expression in childhood
      myelodysplastic syndrome].
AB  - OBJECTIVE: To investigate the expression of the Wilms' tumor 1 (WT1) mRNA in
      childhood myelodysplastic syndrome (MDS), and to evaluate WT1 as a tool to
      differentiate MDS from aplastic anemia(AA). METHODS: The quantitative expression
      of WT1 transcript by using real-time quantitative polymerase chain reaction (RQ
      PCR) was performed in the bone marrow samples of 36 childhood MDS and 49
      childhood AA, the samples were collected from September 2008 to December 2011.
      RESULTS: (1) The positive rate of WT1 in severe AA (SAA) was 0, 14.3% in chronic
      AA (CAA), 58.6% in refractory cytopenia (RC), 100% in refractory anemia with
      excessive blast (RAEB) and 97.5% in acute myeloid leukemia (AML). The mean level
      of WT1 in SAA, CAA, RC, RAEB and AML was 0.041%, 0.357%, 7.037%, 12.680% and
      24.210%, respectively. The positive rate of WT1 in RC patients was higher than
      that of SAA (P = 0.000) and CAA (P = 0.001). (2) The positive rate of WT1 in
      patients with hypoplastic MDS was 66.7% and was higher than that of SAA (P =
      0.000) and CAA (P = 0.001). The mean level of WT1 in patients with hypoplastic
      MDS was (3.022 +/- 5.040)% and higher than that of SAA ?[(0.041 +/- 0.047)%, P =
      0.000?] and CAA?[(0.351 +/- 0.479)%, P = 0.002?]. CONCLUSIONS: The level of WT1
      in childhood MDS was higher than that of childhood AA. The degree of WT1
      expression in MDS increased during disease progression. WT1 is a useful tool for
      differentiating the childhood hypoplastic MDS from AA.

PMID- 22967414
TI  - [Screening and expression of CD34(+) cell-specific microRNA in acute myelogenous
      leukemia].
AB  - OBJECTIVE: To screen and analyze CD34(+) cell specific microRNAs (miRNAs) from
      the patients with acute myelogenous leukemia (AML) and their expression. METHODS:
      CD34(+) cells were sorted from AML patients or the mobilized peripheral blood of
      the donors of hematopoietic stem cell transplantation (normal control subjects)
      and followed by the extraction of the cell total RNAs. The differentially
      expressed microRNAs (miRNAs, miR) were selected after hybridizing with miRNA
      microarray, real time polymerase chain reaction (real-time PCR) was subsequently
      applied to confirm the expression of the selected miRs, and PCR products were
      further cloned and sequenced to check their specificity. RESULTS: Of the
      differentially expressed miRNAs, 191 were found to be at least one-fold change in
      the CD34(+) cells between the AML patients and the normal control subjects. Of
      the 191 miRNAs, the expression difference of 94 was significant (P < 0.05). Among
      these 94 miRNAs, the expression of 44 miRNAs was increased and the other 50
      miRNAs was decreased in the CD34(+) cells from the bone marrow of AML patients
      compared with the CD34(+) cells from the mobilized peripheral blood of the normal
      control subjects. Real time PCR verified that the expression level of miR-10a and
      miR-220c in the CD34(+) cells from the bone marrow of AML patients was 19.6% and
      19.0% of that of CD34(+) cells from mobilized peripheral blood of the normal
      control subjects. DNA sequencing and BLAST DNA database searching results
      indicated that the PCR products were really miR-10a and miR-220c. CONCLUSION: A
      variety of differentially expressed-miRNAs are existed between AML and normal
      control subjects CD34(+) cells, the expression of miR-10a and miR-220c was
      significantly down-regulated in the CD34(+) cells from the bone marrow of AML
      patients.

PMID- 22967415
TI  - [microRNAs expression profile in acute promyelocytic leukemia cell
      differentiation induced by all-trans retinoic acid and arsenic trioxide].
AB  - OBJECTIVE: To study the expression profile of microRNAs in acute promyelocytic
      leukemia (APL) cells during differentiation. METHODS: Differentiation of APL cell
      line NB4 cells was induced by all-trans retinoic acid (ATRA) and arsenic trioxide
      (As2O3). Morphological and immunological assay was performed by Wright-Giemsa
      staining and flow-cytometric analysis of CD11b surface expression. During in
      vitro NB4 differentiation induced by ATRA and As2O3, microRNA expression profiles
      (miR-15b, miR-16, miR-34a, miR-107, miR-124a, miR-146, miR-155, miR-181a, miR
      223, miR-342, let7c) were detected by real time RT-PCR, and the relative
      expression level of microRNAs were quantitatively analyzed by using 2(
      DeltaDeltaCt), and compared with that of control group. Meanwhile, the microRNA
      expression profiles were also detected in 15 newly diagnosed APL patients and 15
      complete remission (CR) APL cases by real time RT-PCR, and the relative
      expression level of microRNA was quantitated by using 2(-DeltaCt), and compared
      with that of control group (newly diagnosed APL as control group). These data
      were expressed as x(-) +/- s, and differences between groups were examined using
      t test. P < 0.05 was considered statistically significant. RESULTS: The
      expression levels of miR-15b, miR-16, miR-107, miR-223 and miR-342 in NB4
      differentiation group were obviously up-regulated (3.40, 4.22, 5.41, 20.03 and
      5.29 folds higher in ATRA treated NB4 cells than that of control group
      respectively, and 3.62, 2.49, 2.58, 4.27 and 1.94 folds higher in AS2O3 treated
      NB4 cells than that of control group respectively), except for miR-15b, the
      expression levels of miR-16, miR-107, miR-223 and miR-342 in ATRA treated group
      was significantly higher than that in As2O3 treated group. The relative
      expression levels of miR-15b, miR-16, miR-107, miR-181a, miR-223 and miR-342 were
      0.4137, 0.6367, 0.1260, 0.0522, 0.6611, 0.0280 in APL CR group, and 0.0751,
      0.2022, 0.0425, 0.3064, 0.1733, 0.0090 in newly diagnosed APL group,
      respectively. The expression level of miR-15b, miR-16, miR-107, miR-223 and miR
      342 in APL CR group were significantly upregulated compared with that of newly
      diagnosed APL groups (P < 0.05), while the expression level of miR-181a was
      significantly downregulated (P < 0.05). CONCLUSION: Specific expression of
      microRNA profiles is a key contributing factor in the differentiation of APL.

PMID- 22967416
TI  - [Clinical features and gene analyses of six patients with MYH9-related disease].
AB  - OBJECTIVE: To investigate clinical features and to identify gene mutations in six
      patients with nonmuscle myosin heavy chain 9 gene (MYH9)-related disease.
      METHODS: The platelet counts were measured using automated complete blood cell
      counter and manual manner. The size of platelets and inclusion bodies were
      observed under light microscopy. All the 40 exons and exon-intron boundaries of
      MYH9 gene were amplified by PCR and then DNA sequencing was performed.
      Restriction endonuclease analysis and polyacrylamide gel electrophoresis (PAGE)
      were used for polymorphism analysis. RESULTS: Six patients all shared the common
      features of thrombocytopenia with giant platelets and granulocyte inclusions.
      Four MYH9 gene mutations were found in the six patients: T97C (W33R) in exon 1,
      4335Insert CAGAAGAAG (1445InsQKK) and G4269A (D1424N) in exon 30 and G5833T
      (E1945Stop) in exon 40. The former two were novel mutations which have not been
      reported in the literature. The results of restriction endonuclease analysis and
      PAGE could exclude the possibility of nucleotide polymorphisms. CONCLUSIONS: The
      MYH9 gene mutations were identified in six patients with MYH9 related disorders,
      and T97C (W33R) and 4335InsCAGAAGAAG (1445InsQKK) were novel mutations. MYH9
      related disease should be considered in individuals with persistent
      thrombocytopenia which is non-responsive to corticosteroids and immuno-repressive
      agents.

PMID- 22967417
TI  - [Expression of SOX11 mRNA in mantle cell lymphoma and its clinical significance].
AB  - OBJECTIVE: To investigate the expression level of SOX11 mRNA in mantle cell
      lymphoma (MCL) and other B-cell non-Hodgkin lymphoma (B-NHL) and its prognostic
      value in MCL. METHODS: The expression level of SOX11 mRNA in 80 B-NHL patients
      were determined by real-time quantitative RT-PCR, GAPDH was used as internal
      control. The dispersion of SOX11 expression ratio of groups with different
      prognostic factors was described by Mann-Whitney U test. RESULTS: The SOX11 mRNA
      expression level was 2.90 (0.75 - 4.63) in 80 B-NHL patients, and the expression
      level was significantly higher in MCL than that in other B-NHL (P = 0.014). The
      SOX11 expression level was statistically lower in the group of MCL with
      hyperleukocytosis, 12 trisomy, MYC amplification and therapeutic effect < PR (P =
      0.042, 0.013, 0.028, 0.009) than that of MCL in other group. But SOX11 expression
      was not associated with MCL international prognostic index (MIPI) (P = 0.333),
      lactate dehydrogenase (LDH) (P = 0.790), ATM mutation (P = 0.865) and P53
      deletion (P = 0.116). The progression free survival (PFS) and overall survival
      (OS) were significantly longer in the MCL patients with high level of SOX11 than
      that of other MCL patients. CONCLUSION: There was statistically significant
      differences in SOX11 mRNA expression between MCL with other B-NHL. SOX11 maybe a
      good prognostic factor in MCL.

PMID- 22967418
TI  - [Discussion on the clinical indications for blood transfusion in anemia of
      prematurity].
AB  - OBJECTIVE: To compare the effect of different indications of blood transfusion on
      the treatment and complications in anemia of prematurity, and to investigate the
      suitable and reasonable indication of blood transfusion for our country. METHODS:
      Ninety six hospitalized premature infants with birth weight less than 1500g and
      stay in hospital equal or more than 2 weeks were enrolled in the retrospective
      study and divided into two groups according to different indications of blood
      transfusion. There are 54 cases in observation group 1 (with strict indications
      for transfusion) and 42 cases in observation group 2 (with loose indications for
      transfusion). RESULTS: In the observation group 1, the total amount of blood
      transfusion ?[M(P25, P75):71.0(43.25, 107.25) ml?] and the times of blood
      transfusion ?[3.00 (2.00, 4.00) times?] are both higher than those of the
      observation group 2 ?[36.0 (29.50, 56.25) ml and 1.50 (1.00, 2.25) times,
      respectively, P = 0.00 1?]. The days of mechanical ventilation and the days of
      continuous positive airway pressure were more in the observation group 1, but
      oxygen supplement in the two groups had no significant difference. In observation
      group 1, the incidence of intracranial hemorrhage, fungal infection rate and
      mortality were higher than those of the observation group 2 (P < 0.05).
      CONCLUSIONS: Anemia of prematurity easily led to the complications, and had
      obvious influence on the survival of premature infants. Clinician should consider
      concrete conditions of every patient before blood transfusion. It has positive
      significance on the survival of premature infants to loosen the indication
      properly and make the use of blood scientifically and rationally.

PMID- 22967419
TI  - [ALK positive large B-cell lymphoma: a case report].

PMID- 22967420
TI  - [Clinical features and antimicrobial resistance of Gram positive bacterial blood
      stream infection in patients with hematologic diseases].
AB  - OBJECTIVE: To study the clinical characteristics and antimicrobial resistance of
      bloodstream infections caused by Gram positive bacteria, so as to provide
      reference for the rational use of antimicrobial agent. METHODS: One hundred and
      eight patients with bloodstream infections of Gram positive bacteria in our
      hospital from January 2009 to December 2009 were retrospectively reviewed. The
      clinical manifestations, pathogen types and antimicrobial susceptibility results
      of pathogens isolated from bloodstream were analyzed. RESULTS: All patients had
      fever and 31.89% with rigor, 22.41% of the patients had no local infection
      lesions, 77.59% had clear infection lesions, including oral infections,
      respiratory tract infections and soft tissue infections. The pathogen testing
      showed that 12.82% were staphylococci aureus, 50.42% coagulase-negative
      staphylococci, 24.8% streptococci, 9.4% enterococci and 2.56% Listeria
      monocytogenes. Antibiotics resistance of staphylococcus and enterococci in our
      hospital was severe. The percentage of methicillin-resistant staphylococcus
      aureus in this investigation was 68.92%. The resistant rates of methicillin
      resistant coagulase-negative staphylococci (MRCNS) to the most antimicrobial
      agents were higher than that methicillin-sensitive coagulase-negative
      staphylococci. One strain of MRCNS was found resistant to teicoplanin and
      linezolid, and 1 strain of enterococci resistant to teicoplanin and linezolid.
      CONCLUSION: Gram positive bacteria shows serious drug resistance, but still keeps
      highly sensitive to vancomycin, linezolid, teicoplanin and
      quinupristin/dalfopristin.

PMID- 22967421
TI  - [Effect of Gli1 gene silencing on proliferation of K562 cells and its
      mechanisms].
AB  - OBJECTIVE: To investigate the effect of Gli1 gene silencing by RNA interference
      (RNAi) on proliferation of K562 cells and its mechanisms. METHODS: The small
      interference RNA (siRNA) was synthesized in vitro. K562 cells were transfected
      with Gli1 siRNA by the way of lipofection (lipofectamine 2000). Non-specific
      siRNA transfected cells were used as control. Transfection efficiencies of
      different siRNA concentrations were detected by flow cytometry and the best siRNA
      concentration was selected. The silencing effect of siRNA was demonstrated by
      real time PCR and Westem blot analysis. Cell proliferation was measured by MTT
      method, cell cycle by PI assay, c-myc and p21 mRNA level was detected by real
      time PCR analysis. RESULTS: Transfection efficiency of siRNA was increased in a
      dose-dependent manner when siRNA concentration was below 200 pmol, and the
      highest transfection efficiency reached (80.11 +/- 5.63)%. Both the mRNA and
      protein level of Gli1 was down-regulated in Gli1 specific siRNA group, the mRNA
      level was (52.60 +/- 3.57)% of that of control group after 24 h (t = 20.33, P <
      0.01) and the protein level was (79.31 +/- 5.58)% of that of control group after
      48 h (t = 6.54, P < 0.01). The cell proliferation rate in Gli1 siRNA group was
      (94.41 +/- 3.58)% (t = 2.40, P = 0.05) and (90.22 +/- 3.34)% (t = 4.37, P < 0.01)
      of that of control group after 24 h and 48 h, respectively. G(2)/M cell cycle
      arrest was observed, the mRNA level of c-myc was down-regulated while p21 was up
      regulated in Gli1 siRNA group after 24 h and 48 h (P < 0.05). CONCLUSIONS:
      Targeted silencing of Gli1 gene by RNAi inhibits the proliferation of K562 cells,
      which acts through the down-regulation of c-myc and up-regulation of p21
      expression.

PMID- 22967422
TI  - [Effective treatment of myelodysplastic syndromes-refractory anemia with excess
      blasts type II by decitabine: a case report].

PMID- 22967423
TI  - [Impact analysis of comorbidities on prognosis of myelodysplastic syndromes
      patients].

PMID- 22967424
TI  - [Study on circulating follicular T helper cell number in the patients with low
      and intermediate- I risk myelodysplastic syndromes].

PMID- 22967425
TI  - [Detection and analysis of IDH, JAK2, FLT3, NPM1 and c-KIT genes mutations in
      myelodysplastic syndromes].

PMID- 22967426
TI  - [Analysis on the plasma level of alpha2 -antiplasmin and Arg6Trp C/T gene
      polymorphism in 102 venous thromboembolism patients].

PMID- 22967427
TI  - [Heparin-induced thrombocytopenia and crossreactivity study between anti
      heparin/platelet factor 4 -antibody and low molecular weight heparin].

PMID- 22967428
TI  - [Analysis of phenotype and genotype in a Chinese pedigree with inherited
      prothrombin deficiency resulted from a homozygous mutation Tyr510Asp].

PMID- 22967429
TI  - [The clinical features, therapeutic effects and prognostic factors analysis for
      follicular lymphoma].

PMID- 22967430
TI  - [The evolutionary cellular entity, epigenetic alteration and microenvironment of
      myelodysplastic syndrome].

PMID- 22967431
TI  - [Research focus on multiple myeloma at the 53rd American Society of Hematology
      meeting].

PMID- 22967433
TI  - A crisis resolution and home treatment team in Norway: a longitudinal survey
      study Part 3. Changes in morbidity and clinical problems from admission to
      discharge.
AB  - BACKGROUND: Crisis resolution and home treatment (CRHT) is an emerging mode of
      delivering acute mental health care in the community. There is a paucity of
      knowledge regarding the workings of CRHT in the literature. This is the third
      paper in a series of three from the longitudinal survey of patients of a CRHT
      team in Norway, which was aimed at describing the characteristics of patients
      served, professional services provided, and clinical outcomes. This report
      focuses on the changes in morbidity and clinical problems from admission to
      discharge and the length of service. METHODS: The study was a descriptive,
      quantitative study based on the patient data from a longitudinal survey of one
      CRHT team in Norway. The participants of the survey, a total of 363 patients,
      were the complete registration of patients of this team in the period from
      February 2008 to July 2009. RESULTS: The findings indicate that the patients'
      mental health status improved from admission to discharge, although many patients
      were discharged with the same mental health symptoms as those present at
      admission. However, one third of the patients were discharged with no clinically
      significant mental health problems. The majority of the patients of the CRHT team
      on the other hand seemed to be those with long-standing mental health problems,
      who were likely to be in need of continuing mental health care even after the
      resolution of mental health crises. There is a need for a coordinated system of
      community-based mental health services for patients with long-standing mental
      health problems, within which CRHT teams can play a pivotal role in making
      connections between the crisis-care and the recovery-oriented care. The mean
      length of service was around 15 days with variations by the clinical problem
      types, with the patients in the psychosis group having the shortest duration and
      the patients in the depression group having the longest duration.

PMID- 22967434
TI  - Isolation and characterization of a variant porcine epidemic diarrhea virus in
      China.
AB  - An outbreak of diarrhea in pigs started in Guangdong, South China in January
      2011. Cases were characterized by watery diarrhea, dehydration and vomiting, with
      80-100% morbidity and 50-90% mortality in suckling piglets. The causative agent
      of the diarrhea was ultimately identified as porcine epidemic diarrhea virus
      (PEDV). In this study, we isolated a PEDV strain designated CHGD-01 from piglet
      intestines using Vero cell cultures, and its specific cytopathic effects were
      confirmed in susceptible cells by direct immunofluorescence testing and electron
      microscopy. The complete genome of CHGD-01 was shown to be 28,035 nucleotides in
      length, with a similar structure to that of PEDV reference strains. Phylogenetic
      analyses based on the whole genome revealed that CHGD-01 shared nucleotide
      sequence identities of 98.2-98.4% with two other Chinese isolates reported in the
      same year, thus constituting a new cluster. Amino acid sequence analysis based on
      individual virus genes indicated a close relationship between the spike protein
      gene of CHGD-01 and the field strain KNU0802 in Korea. Its ORF3 and nucleoprotein
      genes, however, were divergent from all other sequenced PEDV isolate clusters and
      therefore formed a new group, suggesting a new variant PEDV isolate in China.
      Further studies will be required to determine the immunogenicity and
      pathogenicity of this new variant.

PMID- 22967436
TI  - Catalytic mechanism in artificial metalloenzyme: QM/MM study of phenylacetylene
      polymerization by rhodium complex encapsulated in apo-Ferritin.
AB  - Artificial metalloenzyme, composed of metal complex(es) and a host protein, is a
      promising way to mimic enzyme catalytic functions or develop novel enzyme-like
      catalysis. However, it is highly challenging to unveil the active site and exact
      reaction mechanism inside artificial metalloenzyme, which is the bottleneck in
      its rational design. We present a QM/MM study of the complicated reaction
      mechanism for the recently developed artificial metalloenzyme system,
      (Rh(nbd).apo-Fr) (nbd = norbornadiene), which is composed of a rhodium complex
      [Rh(nbd)Cl](2) and the recombinant horse L-chain apo-Ferritin. We found that
      binding sites suggested by the X-ray crystal structure, i.e., sites A, B, and C,
      are only precursors/intermediates, not true active sites for polymerization of
      phenylacetylene (PA). A new hydrophobic site, which we name D, is suggested to be
      the most plausible active site for polymerization. Active site D is generated
      after coordination of first monomer PA by extrusion of the Rh(I)(PA) complex to a
      hydrophobic pocket near site B. Polymerization occurs in site D via a Rh(I)
      insertion mechanism. A specific "hydrophobic region" composed by the hydrophobic
      active site D, the nonpolar 4-fold channel, and other hydrophobic residues nearby
      is found to facilitate accumulation, coordination, and insertion of PA for
      polymerization. Our results also demonstrate that the hydrophobic active site D
      can retain the native regio- and stereoselectivity of the Rh-catalyzed
      polymerization of PA without protein. This study highlights the importance of
      theoretical study in mechanistic elucidation and rational design of artificial
      metalloenzymes, indicating that even with X-ray crystal structures at hand we may
      still be far from fully understanding the active site and catalytic mechanism of
      artificial metalloenzymes.

PMID- 22967437
TI  - Cognitive function in association with sex hormones in postmenopausal women.
AB  - Several studies have suggested gender differences in cognitive function, but data
      on the association between sex hormones and cognitive function are contradictory.
      The aim of our randomized double-blind study was to explore the possible
      relations between cognitive function and serum levels of sex hormones, oxytocin
      and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred
      healthy postmenopausal women were randomly assigned to receive estrogen,
      testosterone or placebo treatment for 1 month. The associations of spatial
      ability, verbal fluency and verbal memory with serum levels of estradiol,
      testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I
      were analyzed. Spatial ability showed a negative correlation with serum
      estradiol, estradiol/testosterone ratio, oxytocin levels and a positive
      association with androstanediol levels. Verbal fluency displayed a negative
      relationship with serum levels of testosterone, IGF-I and a positive with
      estradiol/testosterone ratio. Verbal memory displayed a positive correlation to
      androstanediol. Data suggest that not only absolute levels of sex hormones but
      also the balance between estrogen and testosterone and their metabolites may be
      important for cognitive function in women.

PMID- 22967435
TI  - High TWIST1 mRNA expression is associated with poor prognosis in lymph node
      negative and estrogen receptor-positive human breast cancer and is co-expressed
      with stromal as well as ECM related genes.
AB  - INTRODUCTION: The TWIST homolog 1 (TWIST1) is a transcription factor that induces
      epithelial to mesenchymal transition (EMT), a key process in metastasis. The
      purpose of this study was to investigate whether TWIST1 expression predicts
      disease progression in a large breast cancer cohort with long-term clinical
      follow-up, and to reveal the biology related to TWIST1 mediated disease
      progression. METHODS: TWIST1 mRNA expression level was analyzed by quantitative
      real-time reverse polymerase chain reaction (RT-PCR) in 1,427 primary breast
      cancers. In uni- and multivariate analysis using Cox regression, TWIST1 mRNA
      expression level was associated with metastasis-free survival (MFS), disease-free
      survival (DFS) and overall survival (OS). Separate analyses in lymph node
      negative patients (LNN, n = 778) who did not receive adjuvant systemic therapy,
      before and after stratification into estrogen receptor (ER)-positive (n = 552)
      and ER-negative (n = 226) disease, were also performed. The association of TWIST1
      mRNA with survival endpoints was assessed using Kaplan-Meier analysis. Using gene
      expression arrays, genes showing a significant Spearman rank correlation with
      TWIST1 were used to identify overrepresented Gene Ontology (GO) terms and Kyoto
      Encyclopedia of Genes and Genomes (KEGG)-annotated biological pathways. RESULTS:
      Increased mRNA expression level of TWIST1 analyzed as a continuous variable in
      both uni- and multivariate analysis was associated with shorter MFS in all
      patients (hazard ratio (HR): 1.17, 95% confidence interval, (95% CI):1.09 to
      1.26; and HR: 1.17, 95% CI: 1.08 to 1.26; respectively), in LNN patients (HR:
      1.22, 95% CI: 1.09 to 1.36; and HR: 1.21, 95% CI: 1.07 to 1.36; respectively) and
      in the ER-positive subgroup of LNN patients (HR: 1.34, 95% CI: 1.17 to 1.53; and
      HR: 1.32, 95% CI: 1.14 to 1.53; respectively). Similarly, high TWIST1 expression
      was associated with shorter DFS and OS in all patients and in the LNN/ER-positive
      subgroup. In contrast, no association of TWIST1 mRNA expression with MFS, DFS or
      OS was observed in ER-negative patients. Genes highly correlated with TWIST1 were
      significantly enriched for cell adhesion and ECM-related signaling pathways.
      Furthermore, TWIST1 mRNA was highly expressed in tumor stroma and positively
      related to tumor stromal content (P <0.001). CONCLUSIONS: TWIST1 mRNA expression
      is an independent prognostic factor for poor prognosis in LNN/ER-positive breast
      cancer. The biological associations suggest an involvement of the tumor
      microenvironment in TWIST1's adverse role in breast cancer.

PMID- 22967438
TI  - [Relation of micro-RNA and carcinogenesis].

PMID- 22967439
TI  - [Association between Slit/Robo signal pathway and the genesis, progression,
      invasion and metastasis of malignant tumors].

PMID- 22967440
TI  - [Isolation, purification and characterization of endothelial cells from
      endometrial cancer and normal endometrial tissue].
AB  - OBJECTIVE: To immunopurify human endometrial endothelial cells (HEEC) from fresh
      surgical specimens of endometrial cancers and normal endometrial tissues, and
      investigate their biological characteristics. METHODS: Endothelial cells of
      endometrial cancers and normal endometrial tissues were isolated using anti-CD31
      conjugated magnetic microbeads. The isolated endothelial cells were cultured in
      vitro and their origins were identified. Their angiogenic characteristics were
      observed by MTT, wound healing, Transwell cell invasion and tube formation
      assays. RESULTS: Flow cytometry revealed that the immunopurification technique
      yielded endothelial cell purity of > 95% in all samples. All purified HEEC were
      characterized as endothelial cells on the basis of expression of the classical
      endothelial markers vWF and CD31 as shown by immunofluorescence examination.
      Although the tumor-associated HEEC didn't show more rapid proliferation than
      normal HEEC, they exhibited enhanced migration ability (P = 0.006), potent
      invasiveness (P = 0.033), and elevated tube formation in vitro (P = 0.029).
      CONCLUSIONS: Human endometrial endothelial cells can be efficiently isolated from
      endometrial cancer and normal endometrial tissues by immunomagnetic methods.
      Tumor-associated HEEC exhibit enhanced migratory ability, potent invasiveness,
      and elevated tube formation in vitro.

PMID- 22967441
TI  - [Role of autophagy in quercetin-induced apoptosis in human bladder carcinoma BIU
      87 cells].
AB  - OBJECTIVE: To explore the role of autophagy in quercetin (Que)-induced apoptosis
      in human bladder carcinoma BIU-87 cells in vitro. METHODS: To determine the
      proliferative inhibition by MTT colorimetric assay after treating BIU-87 cells
      with quercetin at various concentrations. To identify autophagy and apoptosis in
      the BIU-87 cells after Que treatment by monodansylcadaverin (MDC) and Hoechst
      33258 fluorescent staining, respectively. To examine the cytotoxic effect of Que
      and influence of autophagy on apoptosis by studying LDH leakage rate and flow
      cytometry, after blocking the autophagy with 3-methlyadenine (3-MA), a specific
      autophagy inhibitor. RESULTS: There was an obvious inhibitory effect of Que on
      the proliferation of BIU-87 cells in a time- and dose-dependent manner. The
      inhibition rate of BIU-87 cells after 200 umol/L Que treatment for 72 hours was
      89.2%. Autophagy and apoptosis were induced and detected in Que-treated BIU-87
      cells and autophagy occurred earlier than apoptosis. The apoptosis peak became
      much higher after the autophagy was blocked. Whenever the autophagy was blocked
      before or after Que treatment, the Que-induced cytotoxicity in BIU-87 cells was
      enhanced. CONCLUSIONS: Quercetin significantly inhibits the proliferation of BIU
      87 cells, and the autophagy is induced earlier than apoptosis. In the process of
      Que-induced apoptosis of BIU-87 cells, autophagy may play a protective role at
      the initiation phase, delay apoptosis and reduce the Que-induced death of BIU-87
      cells.

PMID- 22967442
TI  - [Sensitivity to chemotherapeutic drugs of polyploid tumor cells induced by a
      spindle poison nocodazole].
AB  - OBJECTIVE: To investigate the changes of drug sensitivity of spindle poison
      induced polyploid tumor cells to chemotherapeutic agents and its possible
      mechanism. METHODS: Nocodazole in a dose of 100 ng/ml was used to induce
      polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid
      cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and
      proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells.
      The cell growth inhibition was assessed by MTT assay. The cells were treated with
      paclitaxel, docetaxel, vincristine, epirubicin, 5-Fu, VP16 and oxaliplatin,
      respectively. Those cells were labeled with annexin V-FITC/PI and analyzed by
      flow cytometry. Bcl-2 was knocked down in T-MDA-MB-231 cells using SiRNA and
      their growth inhibition was evaluated by MTT assay to evaluate the reversing
      effect of Bcl-2-silencing on drug resistance. RESULTS: The polyploid T-MDA-MB-231
      cells grew in vitro continuously and maintained constant DNA content. They had a
      larger cell size, and grew more slowly than MDA-MB-231 cells. The IC(50(s)) of T
      MDA-MB-231 cells were significantly higher than that of the MDA-MB-231 cells:
      paclitaxel: (6.37 +/- 0.07) vs. (2.05 +/- 0.83) umol/L; docetaxel: (32.98 +/-
      1.48) vs. (11.95 +/- 0.98) umol/L; vincristine: (35.28 +/- 1.66) vs. (14.58 +/-
      0.94) umol/L; oxaliplatin: (19.07 +/- 0.45) vs. (9.75 +/- 1.05) umol/L; 5-Fu:
      (85.49 +/- 3.21) vs. (31.35 +/- 1.51) umol/L; and epirubicin: (0.53 +/- 0.06) vs.
      (0.15 +/- 0.01) umol/L, (all P < 0.05). The IC(50(s)) of VP16 in T-MDA-MB-231
      cells was (2.85 +/- 0.50)umol/L, significantly lower than the (12.20 +/- 1.55)
      umol/L in MDA-MB-231 cells (P < 0.05), and that of T-MDA-MB-231 cells after Bcl-2
      knocked down by siRNA was (19.59 +/- 0.48) umol/L, significantly higher than the
      (12.20 +/- 1.55) umol/L in the MDA-MB-231 cells (P < 0.05). The IC(50(s)) of
      docetaxel of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (21.52 +/-
      0.68) umol/L, significantly decreased and lower than that before Bcl-2 silencing
      (32.98 +/- 1.48) umol/L. CONCLUSIONS: Our results indicate that polyploid tumor
      cells induced by spindle poison Nocodazole are more resistant to most of
      chemotherapeutic drugs. Downregulation of Bcl-2 increases the sensitivity of
      polyploid cells to docetaxel. The high expression of Bcl-2 may be one of the drug
      resistance mechanisms of polyploid tumor cells. The polyploid tumor cells are
      relatively sensitive to VP16, suggesting that VP16 might be an effective
      candidate drug for treatment of chemoresistant polyploid tumors.

PMID- 22967443
TI  - [DADLE suppresses the proliferation of human liver cancer HepG2 cells by
      activation of PKC pathway and elevates the sensitivity to cis-diammine
      dichloridoplatium].
AB  - OBJECTIVE: To investigate the effect of DADLE, a delta-opioid receptor agonist,
      on the proliferation of human liver cancer HepG2 cells and explore the mechanism
      involving PKC pathway. METHODS: HepG2 cells were treated with DADLE at different
      doses (0.01, 0.1, 1.0 and 10 umol/L). Cell viability was determined using methyl
      thiazolyl terazolium (MTT) assay. The expression of PKC mRNA and p-PKC protein
      were examined by RT-PCR and Western blot assay. After treated separately with
      DADLE plusing NAL or PMA, the cell cycle of HepG2 cells was analyzed by flow
      cytometer. MTT was used to detect their proliferation capacity and Western blot
      was used to examine the p-PKC expression. The growth inhibitory rate of HepG2
      cells treated with DADLE and cis-diammine dichloridoplatinum (CDDP) was analyzed.
      RESULTS: DADLE at different concentrations showed an inhibitory effect on the
      proliferation of HepG2 cells though inhibiting the expression of PKC mRNA and p
      PKC protein. The results of flow cytometry showed that compared with the control
      group, the percentage of S + G(2)/M cells in DADLE-treated group was lowered by
      3.94% (P < 0.01). Meanwhile, after treated with NAL and PMA, the percentage was
      elevated by 3.22% and 3.63%, respectively (P < 0.01). The MTT and Western blot
      assays showed that compared with the control group, the values of A570 and p-PKC
      protein levels in the HepG2 cells of DADLE-treated group were significantly
      decreased (P < 0.01). After treatment with NAL and PMA, the values of A570 and p
      PKC protein levels were elevated significantly (P < 0.01). The growth inhibitory
      rate of DADLE + CDDP group was 79.9%, significantly lower than 25.2% and 43.2% of
      the DADLE and CDDP groups, respectively. CONCLUSIONS: Activation of delta-opioid
      receptor by DADLE inhibits the apoptosis of human liver cancer HepG2 cells. The
      underlying mechanism may be correlated with PKC pathway. DADLE can enhance the
      chemosensitivity of HepG2 cells to CDDP.

PMID- 22967444
TI  - [Effects of downregulation of HDAC6 expression on cell cycle, proliferation and
      migration of laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To detect the expression of histone deacetylase 6 (HDAC6) in laryngeal
      squamous cell carcinoma, and to analyze the effects of downregulation of HDAC6
      expression on cell cycle, proliferation and migration of laryngeal squamous cell
      carcinoma cell line Hep-2 cells, and to explore their possible molecular
      mechanisms. METHODS: Immunohistochemistry was used to detect the expression of
      HDAC6 protein in 55 cases of laryngeal squamous cell carcinoma and 20 cases of
      normal laryngeal mucosa. HDAC6 siRNA and control siRNA were transfected into Hep
      2 cells via lipofectamine 2000, and the interfering effect was analyzed using
      Western blotting. The effects of downregulation of HDAC6 expression on cell
      cycle, proliferation and migration were determined by cell counting kit-8 (CCK
      8), flow cytometry and Boyden chamber, respectively. Finally, Western blotting
      was used to detect the expressions of cell cycle, proliferation and migration
      related proteins. RESULTS: There was a high level expression of HDAC6 protein in
      laryngeal squamous cell carcinoma, and its expression was not related to age and
      sex of the patients (P > 0.05), but closely associated with the degree of
      histological differentiation, TNM staging and lymph node metastasis (P < 0.05).
      HDAC6 siRNA effectively down-regulated the expression of HDAC6 protein in
      laryngeal squamous cell carcinoma cell line Hep-2 cells, and downregulation of
      its expression obviously inhibited cell proliferation, arrested cell cycle at
      G(0)/G(1) phase and decreased cell migration ability in Hep-2 cells.
      Additionally, the downregulation of HDAC6 protein expression markedly decreased
      the expressions of cyclin D1, cyclin E, cdk2 and MMP-9 proteins, but increased
      the expressions of p21 and E-cadherin proteins. CONCLUSIONS: HDAC6 may play a
      pivotal role in the carcinogenesis and development of laryngeal squamous cell
      carcinoma. The downregulation of HDAC6 expression-mediated cell proliferation
      inhibition, cell cycle arrest and decreased cell migration ability may be closely
      associated with the decrease of cyclin D1, cyclin E, cdk2 and MMP-9 proteins and
      increase of p21 and E-cadherin proteins.

PMID- 22967445
TI  - [Expression of ezrin in human non-small cell lung cancer and its relationship
      with metastasis and prognosis].
AB  - OBJECTIVE: To explore the expression of ezrin protein in human non-small cell
      lung cancer (NSCLC) tissues and lung cancer cell lines, and the association
      between the expression of ezrin protein and the expression of E-cadherin and
      CD44V6 proteins. METHODS: The expression of ezrin protein and mRNA in lung cancer
      cell lines was detected by RT-PCR and Western blotting. Ezrin, E-cadherin and
      CD44V6 were detected by immunohistochemical SP staining in tumor tissues from 150
      lung cancer cases and in adjacent normal lung tissues from 30 patients.
      Furthermore, the expression of ezrin in 30 freshly-taken NSCLC tissues was also
      detected by Western blot. RESULTS: The expression of ezrin protein and mRNA was
      up-regulated in highly metastatic human lung cancer. The positive rate of ezrin,
      E-cadherin and CD44V6 expression in the lung cancer was 61.3%, 54.0% and 58.7%,
      respectively. The up-regulation of ezrin expression was significantly correlated
      with lymph node metastasis, but not correlated with age, sex, tumor size,
      histological type, clinical TNM system and pathological grade. Western blot
      analysis showed that the level of ezrin in the NSCLC tissues was significantly
      higher than that in the normal tissues (t = 5.013, P < 0.01). Survival analysis
      showed that the 5-year survival rate of patients with negative ezrin expression
      was 29.3%, significantly higher than that of patients with positive ezrin
      expression (15.2%, chi(2) = 4.128, P = 0.042). Multivariate Cox regression
      analysis showed that ezrin expression (RR = 3.012, P = 0.047) and lymph node
      metastasis (RR = 4.827, P = 0.035) were significantly independent prognostic
      factors for patients with lung cancer. Furthermore, a negative correlation was
      observed between the expressions of ezrin and E-cadherin in lung cancer, and a
      positive correlation between the expressions of ezrin and CD44V6 in lung cancer.
      CONCLUSIONS: Ezrin, E-cadherin and CD44V6 play an important role in the
      regulation of growth and meastasis of lung cancer. Combined detection of ezrin, E
      cadherin and CD44V6 expression is helpful in evaluating the metastasis and
      prognosis of non-small cell lung cancer.

PMID- 22967446
TI  - [DNA methylation status of RARbeta2 and p16(INK4alpha) in peripheral blood and
      tumor tissue in patients with esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To study the methylation status of retinoic acid receptor beta2
      (RARbeta2) and p16(INK4alpha) genes in peripheral blood and tumor tissues and the
      perioperative dynamic changes of free RARbeta2 and p16(INK4alpha) in the
      peripheral blood, and to investigate the relationship between RARbeta2 and
      p16(INK4alpha) methylation in peripheral blood and clinicopathological
      characteristics of esophageal squamous cell carcinoma (ESCC) and their value in
      evaluating the completeness of surgical resection. METHODS: Real-time methylation
      specific polymerase chain reaction (real-time MSP) technique was used to detect
      the methylation status of RARbeta2 and p16(INK4alpha) in tumor tissue, adjacent
      normal tissue and peripheral blood perioperatively in 76 cases of ESCC. Sixty age
      matched healthy volunteers were randomly selected as a control. RESULTS: RARbeta2
      and p16(INK4alpha) hypermethylation presented in both tumor tissue [72.4% (55/76)
      and 86.8% (66/76)] and peripheral blood [63.2% (48/76) and 71.1% (54/76)] in the
      ESCC patients, showing a good agreement between them. RARbeta2 and p16(INK4alpha)
      hypermethylation was significantly related with pathological stage, lymph node
      metastasis, and invasion of nerves and vessels (P < 0.05). The DNA methylation
      rate in peripheral blood was increasing first and then decreasing in the
      preoperative, intraoperative and postoperative periods. Moreover, the RARbeta2
      methylation in peripheral blood was shown to be significantly associated with
      family history of cancer (P = 0.023). CONCLUSION: RARbeta2 and p16(INK4alpha)
      methylation in the peripheral blood in ESCC patients may reflect the tumor
      bearing status in the body, and may serve as a valuable marker in assessment of
      the degree of completeness of surgical resection in ESCC patients.

PMID- 22967447
TI  - [Exploration of the association of H. pylori and EBV infection with cardiac and
      distal gastric adenocarcinoma among residents in Cixian County, a high-risk area
      of esophgeal cancer in Hebei province].
AB  - OBJECTIVE: To evaluate the H. pylori and Epstein-Barr virus infection in cardiac
      and distal gastric adenocarcinoma tissues in residents in Cixian county, a high
      risk area of esophageal cancer in Hebei province, and to explore the putative
      role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of
      adenocarcinoma at different subsites of stomach. METHODS: H. pylori and Epstein
      Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were
      determined by Elivision(TM) plus immunohistochemical staining in 190 gastric
      adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases
      of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein
      Barr virus infection and the subsite, Lauren type as well as other
      clinicopathological features of gastric adenocarcinoma were analyzed. RESULTS: No
      significant difference was found between the H. pylori detection rates in cardiac
      and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate
      of H. pylori in intestinal type was significantly higher than that in the diffuse
      type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive
      expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study.
      CONCLUSIONS: No significant differences in H. pylori and EBV-LMP1 infections were
      found between cardiac and distal gastric adenocarcinomas in Cixian county. H.
      pylori infection is related with the intestinal type of distal gastric
      adenocarcinoma.

PMID- 22967449
TI  - [Influence of the number of removed axillary lymph nodes on the prognosis of node
      negative primary breast cancer].
AB  - OBJECTIVE: To analyze the relationship between the number of removed axillary
      lymph nodes and prognosis of axillary node-negative breast cancer. METHODS: The
      clinicopathological data of 655 patients with breast cancer were analyzed
      retrospectively. The disease-free survival curves were generated according to the
      number of removed axillary lymph nodes using Kaplan-Meier plots. The correlation
      between the co-variables and rate of breast cancer-related events was analyzed
      using Cox model. RESULTS: The overall five year-disease free survival rate of the
      655 cases was 94.4%. The rate of patients with lymph node number <= 12 was 90.3%,
      and that of lymph node number > 12 was 96.5%, with a statistically significant
      difference (P = 0.009). Significantly less breast cancer-related events were
      observed in patients with lymph node number > 12 (15/426, 3.5%) than that in
      patients with lymph node number <= 12 (22/229, 9.6%) (P = 0.009). CONCLUSIONS:
      When axillary node dissection is indicated, dissection of lymph nodes >12 leads
      to much less breast cancer-related events than that in patients with dissected
      lymph node <= 12. The more lymph nodes are dissected, the more accurate prognosis
      can be estimated.

PMID- 22967448
TI  - [Analysis of clinicopathological features of intestinal neuroendocrine
      neoplasms].
AB  - OBJECTIVE: To analyze the clinicopathological features of intestinal
      neuroendocrine neoplasms. METHODS: The clinicopathological features of 114
      patients with intestinal neuroendocrine neoplasms treated in our hospital from
      April 1999 to March 2011 were retrospectively reviewed, including tumor location,
      histological classification, muscle invasion, metastasis and clinical data.
      Immunohistochemical SP staining was applied to examine the expression of 15
      markers in the tumor specimens. RESULTS: The male:female ratio of the patients
      was 1.33, and most of the tumors were located in the rectum of polypoid type. The
      positive rate of immunohistochemical staining of Syn expression was 97.4%, NSE
      95.6%, PGP9.5 84.2%, CD56 75.4%, CD57 72.8%, CgA 43.0%, S100 36.0%, Syn combined
      with CgA 99.1%, and the two marker Syn and CgA combined with any one of CD56,
      CD57 or PGP9.5 reached to 100%. The 5-years survival rates of G1, G2 were 98.9%
      and 76.9%, respectively, and the overall 5-year survival rate of intestinal
      neuroendocrine neoplasms was 92.9%. Two of the 7 cases of poor differentiated
      neuroendocrine carcinoma died after operation, another 2 of them lost to follow
      up. Others were still alive during the follow-up. Among the 3 patients with small
      cell carcinoma, two survived for 8 to 24 months after operation, and one lost to
      follow up. Two cases of mixed adenoneuroendocrine carcinoma (MANEC) were still
      surviving during the follow-up. Different histological types of intestinal
      neuroendocrine neoplasms were significantly different in sex, primary tumor site,
      pathological type, tumor size, types of combined tumors, pT stage, aggressive
      nervous and vascular invasion, and metastasis (all P < 0.05). Single factor
      analysis of the intestinal neuroendocrine neoplasms indicated that tumor size (Z
      = -6.334, P < 0.001), histological classification (chi(2) = 31.175, P < 0.001)
      and muscle invasion (chi(2) = 63.567, P < 0.001) were associated with metastasis
      of intestinal neuroendocrine neoplasms. Logistic analysis showed that muscle
      invasion was the main behavior risk factor of this tumor (OR = 1.827, P < 0.05).
      CONCLUSIONS: Intestinal neuroendocrine neoplasms usually occur in males, and the
      most common involved organ is the rectum. Their histological types are related to
      the prognosis, and the depth of invasion is an important metastasis factor of
      intestinal neuroendocrine neoplasms. Of the neuroendocrine makers, the
      combination of CgA and Syn shows a higher diagnostic sensitivity.

PMID- 22967450
TI  - [Preliminary experience of clinical applications of the 7th UICC-AJCC TNM staging
      system of esophageal carcinoma].
AB  - OBJECTIVE: To compare the instructive value of the 6th and 7th editions of the
      UICC-AJCC staging system in prognosis of esophageal cancer (EC) patients.
      METHODS: The staging and prognosis of 1397 esophageal carcinoma patients
      undergoing curative resection from Jan. 2003 to Dec. 2006 in our hospital were
      retrospectively reviewed and analyzed according to the 6th AJCC staging system
      and the 7th UICC-AJCC staging system. RESULTS: The 5-year overall survival (OS)
      of EC patients with curative resection was 38.5% (481/1250 cases), with a follow
      up rate of 89.5% (1250/1397 case). In overall terms, both the editions were
      statistically significant discriminators of OS (P < 0.05). The 5-year OS of
      stages I, II and III patients were 64.9%, 43.5%, 25.2% according to the 6th
      edition, and 63.5%, 44.5%, 23.5% according to the 7th edition, respectively.
      Distinct differences in survival were present among patients categorized as stage
      Ia and Ib according to the 7th edition (P < 0.05), with a 5-year OS of 80.0% and
      58.3%, respectively. Similarly, according to the 7th edition, the 5-year overall
      survivals (OS) of the stages IIIa, IIIb and IIIc patients were 28.2%, 18.4% and
      16.7%, respectively, showing that the prognoses were significantly different (P <
      0.05). In addition, according to the 7th edition, the prognoses of patients in
      stages N0, N1, N2 and N3 were also significantly different (P < 0.01), and the 5
      year OS were 50.0%, 31.5%, 18.7% and 16.7%, respectively. CONCLUSIONS: Both the
      6th and 7th editions of UICC-AJCC staging system are significant discriminators
      for survival of esophageal cancer patients. The 7th edition is proved to be more
      accurate in prognosis. The number of lymph node metastases is an important
      predictor of prognosis.

PMID- 22967451
TI  - [Docetaxel plus carboplatin versus EC-T as adjuvant chemotherapy for triple
      negative breast cancer: safety data from a phase III randomized open-label
      trial].
AB  - OBJECTIVE: Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)
      /HER2-] breast cancer (TNBC) accounts for ~ 15% of overall breast cancer and
      associated with a poor prognosis. There is a short of standard adjuvant
      chemotherapy regimens for TNBC. A number of studies have shown that TNBC might be
      sensitive to cisplatin and carboplatin on the basis that dysfunction of BRCA1 and
      its pathway is associated with a specific DNA-repair defect, but data of adjuvant
      setting about this is limited. METHODS: From January 2010 to September 2011, 95
      early triple-negative breast cancer patients confirmed by pathology were randomly
      assigned to receive TP (docetaxel 75 mg/m2, carboplatin AUC = 5, day 1, 21 days a
      cycle for 6 cycles) or EC-T (epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2, d1,
      21 days a cycle for 4 cycles, followed by docetaxel 80 mg/m2, d1, 21 days a cycle
      for 4 cycles) chemotherapy. Adjuvant radiation therapy was given selectively
      after chemotherapy. Here we report a preliminary safety analysis with the chi
      square test. RESULTS: Seventy-six out of the 95 patients had completed the
      chemotherapy and could be assessed for the safety profiles of the regimens.
      Thirty-seven of them were in the EC-T group with a median age of 47 years, and 21
      out of these 37 patients were premenopausal (56.8%). Another 39 patients came
      from the TP group with a median age of 46 years, and 22 out of these 39 patients
      were premenopausal (56.4%). All of the 37 patients in EC-T group completed the
      planned treatment whereas 2 patients of the 39 cases in TP group did not because
      of bone marrow suppression. During the treatments, 9 patients had dose adjustment
      in each group. Adverse events of grade 1/2 were common. Specific incidence of
      adverse events with grade 3/4 in each group was as follows: alopecia, 29.7% vs.
      10.3% (P = 0.033), vomiting 21.6% vs. 7.7% (P = 0.085), leukopenia 54.1% vs.25.6%
      (P = 0.011) and neutropenia 51.4% vs. 35.9% (P = 0.174). Other grade 3/4
      toxicities were rare. All the adverse events (except peripheral neuropathy and
      pigmentation) recovered within 1 month after the chemotherapy. CONCLUSION: Both
      EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the
      treatment of triple-negative breast cancer patients, while the TP regimen has
      advantages with less grade III/IV alopecia and leukopenia.

PMID- 22967452
TI  - [Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients
      after autologous hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the effect of recombinant human interleukin 11 (rhIL-11)
      on hematological recovery after autologous hematopoietic stem cell
      transplantation (AHSCT) in patients with lymphoma. METHODS: A retrospective study
      was carried out on 73 patients with lymphoma after AHSCT. The patients were
      divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily
      from the fifth day after AHSCT to the day when platelets recovering to
      80.0*109/L. The control group (n = 38) did not receive rhIL-11 after AHSCT.
      RESULTS: All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our
      department. Thirty-five patients received rhIL-11 and 38 patients did not. In the
      rhIL-11 group and control group, the nadir of platelet was (18.9 +/- 5.0)*109/L
      and (21.5 +/- 6.0)*109/L, respectively, with a significant difference (P = 0.04).
      The median time of platelet recovering to 50.0*109/L was (14.3 +/- 5.5) d and
      (13.2 +/- 4.5) d (P = 0.37) in the two groups. There was no significant
      difference (P = 0.82) in the median numbers of platelet transfusion in the two
      groups. The curves of the mean of daily absolute platelet counts of the two
      groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found
      in the rhIL-11 group. CONCLUSION: The results of this study do not show obviously
      accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients
      after AHSCT and obvious increase of adverse events after rhIL-11 administration.

PMID- 22967453
TI  - [Long-term outcome of CO2 laser microlaryngoscopic treatment for laryngeal
      cancer].
AB  - OBJECTIVE: To investigate the long-term outcome of CO2 laser microsurgery for
      laryngeal cancer. METHODS: Seventy patients with laryngeal cancer were treated
      with CO2 laser microsurgery. All patients were followed up for at least 36 months
      (36 - 108 months). RESULTS: During the 36-108 months follow-up, 64 patients were
      alive, and 6 patients died of recurrence. The total 5-year survival rate was
      91.4%, 5-year local control rate was 81.4%, 5-year local recurrence rate was
      18.6%, and the neck metastasis rate was 4.3%. All survivals had normal breathing
      and good phonation. CONCLUSIONS: The long-term outcomes of CO2 laser microsurgery
      for laryngeal cancer are good, with rapid recovery and few complications, well
      protected laryngeal function and quite good quality of life. Laser surgery should
      be the priority of treatment for early stage laryngeal cancer. However, laser
      surgery for advanced laryngeal cancers and supraglottic laryngeal cancers should
      be carefully chosen.

PMID- 22967454
TI  - [Application of Qu single abdominal aorta clamping for bloodless hepatectomy and
      Pringle hepatectomy in 118 cases of liver tumors].
AB  - OBJECTIVE: To compare the results of application of Qu single abdominal aorta
      clamping for bloodless hepatectomy and Pringle hepatectomy in 118 cases of liver
      tumors. METHODS: The clinical data of 118 patients, including 59 patients
      undergoing Qu single abdominal aorta clamping for bloodless hepatectomy (Group
      QG) and 59 patients undergone Pringle first hepatic portal clamping hepatectomy
      (Group PG) since March 2009 in the Ningbo Tumor Hospital and Jiangxi Provincial
      Hospital were retrospectively reviewed. The changes of blood pressure, oxygen
      saturation, urine volume, intravenous fluid volume, amount of bleeding, time of
      abdominal aorta (or first hepatic portal) clamping, duration of operation and
      anesthesia, and other intraoperative indexes of the two groups were compared, and
      the changes of peritoneal drainage, blood tests, liver functions, etc. before
      operation and 1, 3, 7, 14 days after the hepatectomy in the two groups were also
      analyzed. RESULTS: After taking appropriate measures for intraoperative blood
      pressure control, only small fluctuations of blood pressure, which could be
      safely adjusted and controlled with stable vital signs, was observed in the group
      QG. The amount of intraoperative bleeding in the group QG was (96.25 +/- 18.45)
      ml, significantly less than (536.25 +/- 35.65) ml in the group PG (P < 0.05). In
      the group QG, both the duration of operation time [(227.58 +/- 28.20) min] and
      duration of anesthesia [(249.48 +/- 31.35) min] were significantly shorter than
      that [(261.46 +/- 32.12) min and (286.58 +/- 35.62) min, respectively] in the
      group PG (both P < 0.05). The postoperative liver dysfunction in the group QG was
      also milder than that in the group PG (P < 0.05). CONCLUSIONS: For liver tumor
      patients, Qu single abdominal aorta clamping for bloodless hepatectomy can
      basically achieve the goal of bloodless hepatectomy. This surgical operation is
      simple and safe, worthy of recommendation to skillful liver surgeons in hospitals
      there are some difficulties of blood supply.

PMID- 22967455
TI  - The role of surface chemistry-induced cell characteristics on nonviral gene
      delivery to mouse fibroblasts.
AB  - BACKGROUND: Gene delivery approaches serve as a platform to modify gene
      expression of a cell population with applications including functional genomics,
      tissue engineering, and gene therapy. The delivery of exogenous genetic material
      via nonviral vectors has proven to be less toxic and to cause less of an immune
      response in comparison to viral vectors, but with decreased efficiency of gene
      transfer. Attempts have been made to improve nonviral gene transfer efficiency by
      modifying physicochemical properties of gene delivery vectors as well as
      developing new delivery techniques. In order to further improve and understand
      nonviral gene delivery, our approach focuses on the cell-material interface,
      since materials are known to modulate cell behavior, potentially rendering cells
      more responsive to nonviral gene transfer. In this study, self-assembled
      monolayers of alkanethiols on gold were employed as model biomaterial interfaces
      with varying surface chemistries. NIH/3T3 mouse fibroblasts were seeded on the
      modified surfaces and transfected using either lipid- or polymer- based
      complexing agents. RESULTS: Transfection was increased in cells on charged
      hydrophilic surfaces presenting carboxylic acid terminal functional groups, while
      cells on uncharged hydrophobic surfaces presenting methyl terminations
      demonstrated reduced transfection for both complexing agents. Surface-induced
      cellular characteristics that were hypothesized to affect nonviral gene transfer
      were subsequently investigated. Cells on charged hydrophilic surfaces presented
      higher cell densities, more cell spreading, more cells with ellipsoid
      morphologies, and increased quantities of focal adhesions and cytoskeleton
      features within cells, in contrast to cell on uncharged hydrophobic surfaces, and
      these cell behaviors were subsequently correlated to transfection
      characteristics. CONCLUSIONS: Extracellular influences on nonviral gene delivery
      were investigated by evaluating the upregulation and downregulation of transgene
      expression as a function of the cell behaviors induced by changes in the cells'
      microenvronments. This study demonstrates that simple surface modifications can
      lead to changes in the efficiency of nonviral gene delivery. In addition,
      statistically significant differences in various surface-induced cell
      characteristics were statistically correlated to transfection trends in
      fibroblasts using both lipid and polymer mediated DNA delivery approaches. The
      correlations between the evaluated complexing agents and cell behaviors (cell
      density, spreading, shape, cytoskeleton, focal adhesions, and viability) suggest
      that polymer-mediated transfection is correlated to cell morphological traits
      while lipid-mediated transfection correlates to proliferative characteristics.

PMID- 22967456
TI  - Early postnatal low-protein nutrition, metabolic programming and the autonomic
      nervous system in adult life.
AB  - Protein restriction during lactation has been used as a rat model of metabolic
      programming to study the impact of perinatal malnutrition on adult metabolism. In
      contrast to protein restriction during fetal life, protein restriction during
      lactation did not appear to cause either obesity or the hallmarks of metabolic
      syndrome, such as hyperinsulinemia, when individuals reached adulthood. However,
      protein restriction provokes body underweight and hypoinsulinemia. This review is
      focused on the regulation of insulin secretion and the influence of the autonomic
      nervous system (ANS) in adult rats that were protein-malnourished during
      lactation. The data available on the topic suggest that the perinatal phase of
      lactation, when insulted by protein deficit, imprints the adult metabolism and
      thereby alters the glycemic control. Although hypoinsulinemia programs adult rats
      to maintain normoglycemia, pancreatic beta-cells are less sensitive to secretion
      stimuli, such as glucose and cholinergic agents. These pancreatic dysfunctions
      may be attributed to an imbalance of ANS activity recorded in adult rats that
      experienced maternal protein restriction.

PMID- 22967457
TI  - Fatigue, general health, and ischemic heart disease in older adults.
AB  - BACKGROUNDS: Fatigue has been shown to predict ischemic heart disease (IHD) and
      mortality in nonsmoking middle-aged men free of cardiovascular disease. The aim
      of this study was to investigate the predictive value of fatigue for IHD and
      general health in nondisabled individuals free of cardiovascular disease and
      older than 70 years. METHODS: The study population was drawn from The
      Longitudinal Study of Aging Danish Twins. In total, 1,696 participants were
      followed up for 2-10 years by questionnaires and 10-16 years through registries.
      Kaplan Meier, Cox Proportional Hazard and logistic regression were used to
      analyze data. Fatigue was measured with the mobility-tiredness scale, and
      multivariable-adjusted models included age, sex, socioeconomic position, life
      style factors, and depression symptomatology. Good general health was defined as
      no hospitalization due to IHD, no self-reported IHD-related diagnoses, no use of
      heart medication, sustained good mobility, and participation at follow-up. IHD
      was defined as first hospitalization due to IHD (ICD10: I20-I25) or death due to
      IHD as primary cause. RESULTS: Participants without fatigue had higher chances of
      a sustained good general health at 2 (odds ratio [OR] = 1.45 confidence interval
      [CI] 95%: 1.08-1.93) and 4 years of follow-up (OR = 1.55 CI 95%: 1.11-2.16),
      compared with participants with fatigue. Further, participants with fatigue had a
      significantly higher hazard of IHD during the 10-16 years of follow-up (hazard
      ratio [HR] = 1.47 CI 95%: 1.08-2.00) compared with participants without fatigue.
      CONCLUSION: We concluded that fatigue in nondisabled older adults free of
      cardiovascular disease is an early predictor for development of subsequent poor
      general health and IHD.

PMID- 22967458
TI  - Functional status of older nursing home residents can affect the efficacy of
      influenza vaccination.
AB  - BACKGROUND: The efficacy of influenza vaccination in older nursing home residents
      is frequently overestimated due to frailty selection bias. Limited data exist to
      examine this issue. METHODS: We conducted a prospective cohort study from
      December 2009 to November 2010 to evaluate the efficacy of influenza vaccination
      in old nursing home residents with respect to their functional status.
      Participants were stratified according to the Barthel Index (BI) into good
      functioning (GF; BI > 60), intermediate functioning (IF; BI = 5-60), and poor
      functioning (PF; BI = 0). Participants were vaccinated by monovalent H1N1 2009
      and trivalent seasonal influenza vaccinations (H1N1-TIV), TIV alone, or remained
      unvaccinated by choice. The associations between all-cause mortality, vaccination
      efficacy, and functional status were examined. RESULTS: A total of 711 older
      nursing home residents were enrolled (GF group: N = 230; IF group: N = 246; PF
      group: N = 235). At 12 months, H1N1-TIV recipients had the lowest all-cause
      mortality, whereas unvaccinated residents had the highest all-cause mortality in
      all three functional status groups. In the comparison between H1N1-TIV recipients
      and TIV alone recipients, the hazard ratios (HRs) of all-cause mortality were
      lower in the GF group and higher in the PF group (GF group: HR 0.30 [0.07-0.95],
      p < .05; IF group: HR 0.40 [0.18-0.86], p < .05; PF group: HR 0.53 [0.28-0.99], p
      < .05). The same observation was found in comparison between other vaccination
      statuses (H1N1-TIV vs unvaccinated and TIV alone vs unvaccinated). CONCLUSIONS:
      Influenza vaccination was associated with reduced all-cause mortality in older
      nursing home residents with different functional statuses. Vaccine efficacy in
      reducing mortality declined with increasingly impaired functional status.

PMID- 22967459
TI  - Association between indicators of disability burden and subsequent depression
      among older persons.
AB  - BACKGROUND: Disability is associated with depression in older persons, yet the
      effect of disability burden on the likelihood of being depressed is uncertain.
      METHODS: A total of 754 community-living persons, aged >=70, underwent monthly
      assessments in four essential activities of daily living and assessments of
      depression (yes/no) every 18 months for up to 108 months. Within each 18-month
      person-interval, participants' disability burden was operationalized as none or
      any, and according to severity (none, mild, or severe) and chronicity (none,
      nonchronic, or chronic) given the highest level of severity or chronicity
      experienced during a given 18-month interval, respectively. A variable combining
      severity and chronicity (none, nonchronic mild, nonchronic severe, chronic-mild,
      or chronic-severe) was also created. Using generalized estimating equations, we
      evaluated the association between each indicator of disability burden and
      subsequent depression. RESULTS: Participants who had any versus no disability
      during the previous 18 months were 65% more likely to experience subsequent
      depression (OR = 1.65; 95% confidence interval [CI] 1.34, 2.02). Quantifying
      severity (mild disability vs. none, OR = 1.43; 95% CI: 1.15, 1.79; severe
      disability vs. none, OR = 2.07; 95% CI 1.56, 2.74) and chronicity (nonchronic
      disability vs. none, OR = 1.44; 95% CI 1.13, 1.83; chronic disability vs. none,
      OR = 1.96; 95% CI 1.50, 2.55) indicated increasingly stronger associations with
      subsequent depression, with the highest likelihood of subsequent depression (OR =
      2.42; 95% CI 1.78, 3.30) observed among participants with chronic-severe
      disability. CONCLUSIONS: Quantifying the magnitude of disability burden,
      particularly on the basis of severity and chronicity, provides additional
      information regarding the likelihood of experiencing subsequent depression among
      older persons.

PMID- 22967460
TI  - Clinical review: Serious adverse events associated with the use of rituximab - a
      critical care perspective.
AB  - The advent of biologic agents has provided a more specific and targeted approach
      to the treatment of various hematological malignancies and other autoimmune
      disorders. Such biologic agents have been relatively well tolerated with fewer
      adverse events reported as compared with many other chemotherapeutic agents.
      Rituximab is a monoclonal antibody to the B-cell marker CD20 and is a common
      biologic agent widely used for the treatment of B-cell lymphoma,
      lymphoproliferative disorders, and inflammatory conditions that are refractory to
      conventional treatment, including rheumatoid arthritis and some vasculitides.
      However, through randomized controlled trials and post-marketing surveillance, an
      increasing number of serious adverse events are being associated with the use of
      rituximab, often leading to or complicating an intensive care unit admission. The
      purpose of this review is to focus on the severe complications that are
      associated with the use of rituximab and that require critical care. Management
      and prevention strategies for the most common complications along with some
      examples of its uses within the critical care setting are also discussed. 

PMID- 22967461
TI  - Enantioselective synthesis of alpha-oxy amides via Umpolung amide synthesis.
AB  - alpha-Oxy amides are prepared through enantioselective synthesis using a sequence
      beginning with a Henry addition of bromonitromethane to aldehydes and finishing
      with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding
      that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline)
      catalyst deliver both diastereomers of the Henry adduct with high enantiomeric
      excess, homochiral at the oxygen-bearing carbon. Overall, this approach to alpha
      oxy amides provides an innovative complement to alternatives that focus almost
      entirely on the enantioselective synthesis of alpha-oxy carboxylic acids.

PMID- 22967462
TI  - [To make great effort to strengthen cancer prevention and research publication].

PMID- 22967463
TI  - [Strategy and perspective of population-based cancer prevention and control in
      China].

PMID- 22967464
TI  - [Establishment of a syngeneic mouse model of liver tumor stably expressing
      hepatitis B virus antigens].
AB  - OBJECTIVE: To establish a syngeneic mouse model of liver tumor stably expressing
      hepatitis B virus (HBV) antigens. METHODS: Melanoma cell line B16 cells were
      transfected with pLXSN-2HBV. Cells (named B16/HBV) stably and persistently
      expressing HBV surface (HBsAg) and core (HBcAg) antigens were identified. The
      cells were injected into the hepatic subcapsular space of fifteen C57BL/6J mice.
      The mice were divided into 3 groups, receiving 100, 1000 or 5000 cells in a total
      volume of 5 ul per mouse, respectively, five mice in each group. Two weeks after
      the tumor cell inoculation, serum samples from the mice were collected weekly and
      the serum concentration of HBsAg and anti-HBs was quantified by ELISA. The tumor
      growth in the mouse liver was monitored by a high-resolution ultrasound system.
      Expression of HBsAg and HBcAg in the tumor tissues was determined by
      immunohistochemistry. RESULTS: Liver tumors were formed in all the mice receiving
      1000 and 5000 B16/HBV cells per mouse, and in 80% of the mice receiving 100
      B16/HBV cells. HBsAg and anti-HBs were detectable in their sera from 2 weeks
      after tumor cell inoculation. The mice receiving 100 cells per mouse began to die
      4 weeks, those receiving 1000 cells per mouse began to die 3 - 4 weeks and those
      receiving 5000 cells began to die 2 - 3 weeks after the cell inoculation. All the
      tumor cells expressed HBsAg and HBcAg. CONCLUSIONS: The B16/HBV cells stably and
      persistently express HBV antigens both in vitro and in vivo. A mouse model of
      transplanted liver tumor stably expressing HBV antigens has been successfully
      established by inoculation of those cells into the hepatic subcapsular space.

PMID- 22967465
TI  - [Effect of trichostatin A and paclitaxel on the growth and apoptosis of lung
      adenocarcinoma cell lines].
AB  - OBJECTIVE: To investigate the effect of trichostatin A (TSA)/paclitaxel on the
      growth and apoptosis in human lung adenocarcinoma cell line A549 cells. METHODS:
      Human lung adenocarcinoma A549 cells were cultured in DMEM in the presence of
      paclitaxel and the histone deacetylase inhibitor trichostatin A, and the growth
      curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was
      assessed using Hoechst 33258 staining and flow cytometry, and cell cycle was
      detected by flow cytometry analysis. The proteins of PARP, caspase-3, survivin
      and tubulin acetylation were detected by Western blotting. RESULTS: Significant
      growth reduction was observed in the A549 cells following treatment with
      paclitaxel or the histone deacetylase inhibitor TSA. The combined treatment with
      TSA/paclitaxel caused the highest inhibition of cell growth. The apoptosis rate
      of A549 cells treated with TSA or paclitaxel for 24 hours was (17.6 +/- 1.8)% and
      (39.2 +/- 3.7)%, respectively, but a significantly higher apoptosis rate was
      (64.2 +/- 4.2)% was induced by combined treatment with TSA and paclitaxel. In
      contrast with the control group, the cell cycle was markedly arrested at G2/M
      phase in the TSA and paclitaxel group (P < 0.05). The Western blot analysis
      demonstrated that treatment with TSA/paclitaxel led to a synergistic increase of
      acetylated tubulin, PARP and caspase-3, and reduced the expression of survivin.
      CONCLUSION: TSA or paclitaxel alone can inhibit the cell growth and induce
      apoptosis, and the combination of TSA and paclitaxel exerts a synergistic effect
      on the growth and apoptosis in lung adenocarcinoma cells.

PMID- 22967467
TI  - [Relationship between single nucleotide polymorphism in repair gene XPD751 and
      prognosis in colorectal carcinoma patients].
AB  - OBJECTIVE: To investigate whether single nucleotide polymorphism (SNP) in DNA
      repair gene XPD751 is associated with sensitivity and time to progression (TTP)
      for platinum-containing combination chemotherapy in advanced colorectal
      carcinoma. METHODS: A total of 98 patients pathologically diagnosed as advanced
      colorectal cancer were treated with FOLFOX chemotherapy. TheDNA of peripheral
      blood-leukocytes was obtained before treatment, and XPD genetype was detected by
      PCR-RFLP analysis. RESULTS: The frequency of XPD751 Lys/lys was 76 cases (77.6%),
      lys/Gln 17 cases (17.4%), and Gln/Gln genetype 5 cases (5.1%). The effective rate
      of FOLFOX chemotherapy among patients with XPD751 Lys/lys was 50.0%, lys/Gln
      29.4%, and Gln/Gln genetypes 20.0%. The difference between Lys/lys and lys/Gln
      was statistically significant, chi(2) = 4.04, P < 0.05. The results indicated
      that the failure of chemotherapy in patients with Lys/Lys genetype was 3.8-fold
      to those with Lys/Gln, by adjusting of gender, age, and tumor metastasis (OR =
      3.800). The MTTP of the 98 patients was 10.1 months. The MTTP was 11.3 months for
      patients with Lys/Lys genotypes of XPD751 gene and 2.9 months for patients with
      Lys/Gln and Gln/Gln genotypes of XPD751 gene, the difference between Lys/Lys and
      at least one Gln was significant (P < 0.05). CONCLUSIONS: Single nucleotide
      polymorphism of XPD751 correlates with the clinical response to FOLFOX
      chemotherapy. XPD751 genetic polymorphisms may be associated with TTP of advanced
      colorectal carcinoma patients treated with oxaliplatin as the first line
      chemotherapy. XPD751 genotype detected by the PCR-RFLP method may be a predictor
      of prognosis for FOLFOX chemotherapy.

PMID- 22967466
TI  - [Expression of PRUNE2 mRNA and its positive correlation with non-coding RNA PCA3
      in leiomyosarcoma].
AB  - OBJECTIVE: Our previous study shows that PURNE2 mRNA plays an important role in
      the differential diagnosis of leiomyosarcoma and gastrointestinal stromal tumor
      (GIST). Non-coding RNA PCA3 locates in the intron of PRUNE2 and may play a role
      in PRUNE2 expression. The aim of this study was to explore the expression of PCA3
      mRNA and PRUNE2 in leiomyosarcoma and their correlation. METHODS: The expression
      of PRUNE2 mRNA was analyzed by agilent gene expression microarray CHIP in 31
      leiomyosarcomas and 37 GISTs, and the correlation of the PRUNE2 expression and
      prognosis of leiomyosarcoma was predicted. Real-Time PCR assay was used to detect
      the mRNA levels of PCA3 and PRUNE2 in 13 leiomyosarcomas and to investigate their
      correlation. Seven prostate cancer tissues were used as control of PCA3. RESULTS:
      The level of PRUNE2 mRNA expression was significantly higher in the 31
      leiomyosarcomas than that in the 37 GISTs, and the level of PRUNE2 mRNA
      expression was correlated with survival of the leiomyosarcoma patients. Compared
      with prostate cancer, the non-coding RNA PCA3 expression level was significantly
      lower in leiomyosarcoma, and it had no correlation with the prognosis of
      leiomyosarcoma. Most importantly, the PRUNE2 and PCA3 mRNA expressions were both
      upregulated in leiomyosarcoma and showed a significant positive correlation.
      CONCLUSIONS: Our findings demonstrate for the first time that PRUNE2 expression
      is correlated with the survival of leiomyosarcoma patients. Furthermore, non
      coding RNA PCA3, which locates in the intron of PRUNE2, has a significant
      positive correlation with PRUNE2 and may play an important role in the
      pathogenesis of leiomyosarcoma.

PMID- 22967468
TI  - [Prognostic value of lymph node ratio in survival of patients with stage III
      rectal cancer].
AB  - OBJECTIVE: To assess the prognostic value of lymph node ratio (LNR) in patients
      with stage III rectal cancer after curative resection. METHODS: A retrospective
      review of the clinicopathological data was performed in 161 patients with stage
      III rectal cancer who received curative surgical excision in our hospital from
      June 2005 to June 2010. The variables including LNR, age, gender, T stage, N
      stage, total number of dissected lymph nodes, number of metastatic lymph nodes,
      and positive rate of lymph node metastasis were studied through univariate and
      multivariate analyses, and the survival analysis was performed using Kaplan-Meier
      method and Log rank test. RESULTS: Multivariate analysis revealed that LNR, but
      not number of positive nodes or number of harvested lymph nodes, had independent
      prognostic value for overall survival and disease-free survival for patients with
      stage III rectal cancer. The overall survival in the LNR < 0.43 and LNR >= 0.43
      groups was 75.8% and 41.3%, respectively (P < 0.01), while the disease-free
      survival was 68.8% and 40.3%, respectively (P = 0.001). CONCLUSIONS: The LNR is
      an independent prognostic factor for survival of patients with stage III rectal
      cancer, and is more efficient than the number of positive nodes and total number
      of dissected lymph nodes in the survival prediction.

PMID- 22967469
TI  - [Analysis of clinicopathological features and prognosis in 68 patients with
      chromophobe renal cell carcinoma].
AB  - OBJECTIVE: To investigate the clinicopathological features and prognosis of
      chromophobe renal cell carcinoma (ChRCC). METHODS: The clinical data of 68 ChRCC
      cases treated in our department between January 2003 and September 2010 were
      collected and retrospectively analyzed. The prognostic factors were evaluated by
      Log-rank test. Kaplan-Meier survival curve was used to estimate the survival
      rate. RESULTS: Fifty cases were treated with radical nephrectomy and 18 with
      partial nephrectomy. The mean tumor size was 5.7 cm (1.5 - 16.0 cm). The TNM
      stages were as follows: pT1aN0M0 in 25, pT1bN0M0 in 22, pT2aN0M0 in 9, pT2bN0M0
      in 5, and pT3aN0M0 in 7. According to the Fuhrman grading system, 8 patients were
      classified as grade I, 42 cases were grade II, 14 cases were grade III, and 4
      cases were grade IV. The 3-year and 5-year survival rates were 93.0% and 90.0%,
      respectively. The log-rank test showed that tumor size (> 7 cm vs. <= 7 cm) (P =
      0.004), TNM stage (T1-2 vs. T3-4) (P = 0.008) and urinary collecting system
      invasion (P = 0.024) were associated with survival time. The multivariable Cox
      regression model revealed that tumor size (> 7 cm vs. <= 7 cm) was an independent
      predictor of aggressive ChRCC (P = 0.038). CONCLUSIONS: ChRCC is a distinct type
      of renal cell carcinoma exhibiting a low degree of malignancy. Most tumors are
      larger, but predominantly with a favorable prognosis. Fuhrman nuclear grading is
      not suitable for ChRCC. Tumor size (> 7 cm vs. <= 7 cm) is an independent
      predictor of prognosis of ChRCC.

PMID- 22967470
TI  - [Surgical treatment of sternal tumors: resection of the tumors and reconstruction
      of the chest wall defects].
AB  - OBJECTIVE: To investigate the efficacy of surgical treatment of sternal tumors
      and repairing methods of the chest wall defects. METHODS: Fifteen patients with
      sternal tumors were diagnosed and underwent resection of the sternal tumors
      according to the en-bolck principle and repair of the chest wall defects using
      various materials from January 1968 to December 2010 in our hospital. RESULTS: Of
      6 patients with sternal manubrim tumors, one patient had reconstruction only with
      steel wire, other 5 patients healed completely after repair with soft materials.
      Of 7 patients with sternal body tumors, one patient recovered quickly without
      reconstruction because he had only partial resection; four patients had chest
      wall repair with soft materials, but they breathed hardly; and two patients had
      chest wall reconstruction with rigid materials. One patient had ventilatory
      support, another patient recovered quickly. Ventilatory support was needed in two
      patients treated by subtotal sternectomy because they had chest wall repair with
      soft materials. CONCLUSIONS: In surgical treatment of sternal tumors by manubrim
      sternetomy, the chest wall defects can be constructed with soft materials. After
      resection of sternal body tumors and subtotal sternectomy, the thoracic wall
      defects need to be reconstructed with rigid materials.

PMID- 22967471
TI  - [Trend analysis and projection of cancer incidence in China between 1989 and
      2008].
AB  - OBJECTIVE: Nationwide cancer incidence data were used to analyze the trends of
      cancer incidence in China in order to provide basic information for making cancer
      control strategy. METHODS: We retrieved and re-sorted valid cancer incidence data
      from the National Central Cancer Registry Database over the 20 year-period 1989
      2008. Crude incidence rate and age-standardized incidence rate were calculated
      for analysis. Annual percent changes in incidence for all cancers combined were
      estimated using Joinpoint software. RESULTS: The cancer incidence rate in cancer
      registration areas was increased from 184.81/10(5) in 1989 to 286.69/10(5) in
      2008 (from 209.33/10(5) to 307.04/10(5) in urban and from 176.10/10(5) to
      269.57/10(5) in rural areas). Uptrends of crude cancer incidence were shown in
      both male and female in urban and rural areas over the 20 year-period. After
      standardized by age, overall incidence rate kept stable with 0.5% annual increase
      in urban and no change in rural areas. Since 2000, the cancer incidences in both
      sexes and areas were significantly increased. The incidence increased for most
      major cancers, especially lung cancer, colorectal cancer, female breast cancer
      and cervical cancer. CONCLUSIONS: Over the 20 year-period 1989-2008, cancer
      incidence of most cancers has been increasing by time. The incidences of gastric
      cancer, liver cancer and esophageal cancer still keep gradually increasing. The
      incidences of lung cancer, female breast cancer, colorectal cancer and cervical
      cancer are markedly going up, so that cancer prevention and control should be
      enhanced. Cancer registration will play an important role on cancer control in
      China along with the number of registries increasing and data quality improving.

PMID- 22967472
TI  - [Trend analysis of cancer mortality in China between 1989 and 2008].
AB  - OBJECTIVE: Cancer is one of the leading causes of death in China. The study aimed
      to examine the temporal trend of cancer mortality rate during 1989-2008 in urban
      and rural areas of China. METHODS: The mortality data of all cancers from 1989 to
      2008 from National Cancer Registry database were sorted and checked. Age
      standardized mortality rates were calculated by the direct methods using the
      China population of 1982 and World Segi's population. Joinpoint regression was
      performed to obtain the annual percentage changes (APC) in mortality rates. The
      top ten cancer sites were calculated and analyzed. The mortality rates were
      compared with statistics of the United States. RESULTS: From 1989 to 2008, the
      trend of crude cancer mortality increased with an annual percentage change (APC)
      of 1.0%. After age standardization, the mortality rate was significantly
      decreased, with an APC of -1.2%. In urban areas, lung cancer was the most common
      cancer of death, whereas in rural areas, stomach cancer and esophageal cancer
      remained top cancers of death. Especially, in both urban and rural areas, the
      mortality of lung cancer was on increase. The mortality rates of stomach and
      esophageal cancers showed a decrease in urban areas. Compared with the cancer
      mortality rates of the United States, the Chinese cancer mortality rate in males
      remained highest. The decreasing trend of cancer mortality in females of China
      was less obvious than that of the United States. CONCLUSIONS: The crude mortality
      rates of cancer in China show an increase whereas the age standardized mortality
      raters has declined between 1989 and 2008. Cancer is still a major public health
      issue threatening people's life in China. Effective intervention for cancer
      control and prevention is needed in the future.

PMID- 22967473
TI  - [Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty
      years].
AB  - OBJECTIVE: To describe and analyze the charecteristics and trends of liver cancer
      mortality during the past fifty years in Qidong, China. METHODS: Retrospective
      mortality survey was conducted to get the data on liver cancer death in the
      period of 1958-1971, and the data from 1972 to 2007 were obtained from the
      records of cancer registration in Qidong. The crude mortality rate (CR) of liver
      cancer, and age-standardized rate by Chinese population (CASR) and by world
      population (WASR) were calculated and analyzed. The total percent changes (PC)
      and annual percent changes (APC) were used for evaluating the increasing trends
      of the mortality. The sex-specific rate, age-specific rate, truncated rate of the
      age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period
      rate, and the rate for age-birth cohort were compared. RESULTS: The natural death
      rate in Qidong residents for the past five-decade period experienced a wave
      interval of 8.620/00 in 1958 down to 5.370/00 in 1979, and up to 7.750/00 in
      2007. The mortality rate for all-site cancers was increased from 56.69 per 100,
      000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per
      100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per
      100, 000 in 2007. According to the registration data of 1972 - 2007, the death
      from liver cancer was accounted for 34.88% of all deaths due to cancers, with a
      CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100,
      000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100,
      000, and the cumulative rate for the age group 0-74 and the cumulative risk were
      5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for
      females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of
      1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing
      variation tendency. The APCs for CASR and WASR, however, were decreasing, with a
      percentage of -1.11%, and -0.84%, respectively. The age-specific mortality rates
      by period showed a decreasing trend for those under age of 44. Moreover, age
      birth cohort analysis showed a more rapid lowering mortality in the age groups 35
      , 30-, 25-, and 15-, that is, those born after 1950's. CONCLUSIONS: Liver cancer
      remains the leading death cause due to cancers in Qidong, with a continuing
      higher crude mortality rate. Yet the age-standardized mortality rate has
      presented a declining posture. The liver cancer mortality in young people in
      Qidong demonstrates a continuously falling trend. The campaign for the control of
      liver cancer in Qidong has achieved initial success.

PMID- 22967474
TI  - [Population-based gastric cancer screening in Zhuanghe, Liaoning, from 1997 to
      2011].
AB  - OBJECTIVE: To investigate the feasibility of gastric cancer screening for the
      susceptible population in the high-risk areas of China and to optimize the
      screening programme. METHODS: By using the two-round screening method i.e. serum
      pepsinogen test combined with gastric mucosa biopsy, large-scale population
      screening programs were carried out in Zhuanghe, Liaoning province. All adults or
      residents above 35 years old with a positive family history of gastric cancer or
      gastrointestinal symptoms were targeted. RESULTS: Three large-scale population
      screenings were developed over the past 15 years. All together, 13078
      participants accepted the two-round screening, and 108 gastric cancer cases were
      detected. Among them, the detection rate of early gastric cancer was 56.82%,
      51.22% and 82.61%, respectively. The pathologically confirmed gastric cancer
      cases were immediately arranged to have early surgical treatment, and meanwhile,
      the follow-up files for the patients were established. With a consecutive and
      regular 10-year postoperative follow-up, the 5-year survival rate for these early
      gastric cancer patients reached 90.48%. Effectiveness and health economic
      evaluation confirmed that there are good specificity and sensitivity for the two
      round screening programs. It is cost-effective. As the primary screening method
      serum PG test can improve the screening examination rate and concentrate the
      gastric cancer risk populations. CONCLUSIONS: It is feasible to develop the
      gastric cancer screening program among the susceptible population in high-risk
      areas in our country, and the two-round screening method is of practical value.
      Research for early detection of gastric cancer should be further enhanced, and
      multidisciplinary and multicenter cooperation should be organized. It is
      necessary to extend the implementation the gastric cancer screening and to
      further improve the early detection programme, in order to make a breakthrough
      based on the present practice.

PMID- 22967475
TI  - [Evaluation of cobas 4800 high-risk HPV test as a tool in cervical cancer
      screening and cytology triage].
AB  - OBJECTIVE: To evaluate the feasibility and reliability of cobas 4800 HPV test for
      cervical cancer screening and cytology referral. METHODS: cobas 4800 HPV test and
      hybrid capture 2 (HC-2) were used to detect high risk HPV DNA in 670 specimens of
      liquid-based cytology collected from three hospitals. The agreement between cobas
      and HC-2 tests was assessed. HPV PCR detection (HybriBio) and gene sequencing
      were used for genotyping, and the agreement of HPV16 and 18 genotyped by cobas
      and HybriBio was evaluated. Histological diagnosis was considered as a gold
      standard to estimate the sensitivity and specificity of cobas vs. HC-2 in
      detecting CIN2(+) in cervical lesions. RESULTS: The crude agreement between cobas
      and HC-2 tests was 89.40%, the Kappa value was 0.778, the positive concordance
      rate was 86.42%, and the negative concordance rate was 91.36%. The crude
      agreement rates between cobas and HybriBio on HPV16 and 18 were 88.89% and
      94.94%, the Kappa values were 0.777 and 0.753, the positive concordance rates
      were 98.91% and 100.00%, and the negative concordance rates were 78.41% and
      94.44%, respectively. HPV PCR detection (HybriBio) and gene sequencing were
      considered as adjusted standard: the high risk HPV positive concordance rate was
      100%, negative coincidence rate was 94.42%, HPV16 and 18 positive concordance
      rates were both 100%, and negative concordance rates were 82.35% and 94.44%,
      respectively. Regarding the detection of CIN2(+), the sensitivity and specificity
      were 91.07% and 70.97% for cobas, and 93.75% and 71.33% for HC-2, with a non
      significant difference between the results of the two tests (P > 0.05).
      CONCLUSIONS: cobas4800 HPV test has good screening sensitivity and specificity in
      correct detection of HPV16 and 18 and other high-risk HPV virus types.

PMID- 22967476
TI  - [Cost-effectiveness evaluation of seven screening strategies for nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To evaluate the cost-effectiveness of different screening strategies
      for nasopharyngeal carcinoma (NPC) and recommend a preferable NPC screening
      strategy. METHODS: A Markov simulation model was constructed based on the natural
      history of NPC. Seven strategies (A. Annual screening; B. Annual screening for
      (Epstein-Barr virus, EBV) EBV-seropositive subjects, triennial screening for
      seronegative subjects; C. Biennial screening; D. Triennial screening; E. 4-year
      screening; F. 5-year screening; G. 6-year screening) were evaluated. The NPC
      pickup rate, cost, quality-adjusted life-years (QALYs) and incremental cost
      effectiveness ratio (ICER) were calculated. RESULTS: The ICERs of the 7
      strategies were 83 111.6, 47 768.9, 50 164.7, 40 016.2, 34 272.8, 32 215.6, and
      32 248.0 Yuan/QALY, respectively. The discounted QALYs of the strategies were 23
      079.9, 22 955.6, 22 810.4, 22 636.5, 22 522.7, 22 445.0, and 22 361.9 years,
      respectively. The ICERs of the strategies were less than three times of the
      average per capita gross domestic product (89 976 Yuan) in China in 2010. The
      strategy A achieved a highest NPC pick-up rate (81.7%), a highest discounted QALY
      and a smallest number of NPC death (681), but a highest discounted cost and a
      greatest ICER. Compared with the strategy A, the strategy B achieved a little
      smaller NPC pick-up rate (73.1%), a little smaller number of NPC death (707),
      however, the ICER of the strategy B decreased by 38.2%. CONCLUSION: The strategy
      B (annual screening for EB virus seropositive subjects and triennial screening
      for seronegative subjects) is a preferable option for NPC screening.

PMID- 22967477
TI  - [Some problems should be paid attention to in research on cancer prevention and
      epidemiology].

PMID- 22967478
TI  - ERP differences between processing of physical characteristics and personality
      attributes.
AB  - BACKGROUND: Limited data from behavioral and brain-imaging studies indicate that
      personality traits and physical characteristics are processed differently by the
      brain. Additionally, electrophysiological results of studies comparing the
      processing of positive and negative words have produced mixed results. It is
      therefore not clear how physical and personality attributes with emotional
      valence (i.e., positive and negative valence) are processed. Thus, this study
      aimed to examine the neural activity associated with words describing personality
      traits and physical characteristics with positive or negative emotional valence
      using Event Related Potentials (ERPs). METHODS: A sample of 15 healthy adults (7
      men, 8 women) participated in a computerized word categorization task.
      Participants were asked to categorize visual word stimuli as physical
      characteristics or personality traits, while ERPs were recorded synchronously.
      RESULTS: Behavioral reaction times to negative physical stimuli were shorter
      compared to negative personality words, however reaction times did not
      significantly differ for positive stimuli. Electrophysiological results showed
      that personality stimuli elicited larger P2 and LPC (Late Positive Component)
      amplitudes compared to physical stimuli, regardless of negative or positive
      valence. Moreover, negative as compared with positive stimuli elicited larger P2
      and LPC amplitudes. CONCLUSION: Personality and physical stimuli were processed
      differently regardless of positive or negative valence. These findings suggest
      that personality traits and physical characteristics are differentially
      classified and are associated with different motivational significance.

PMID- 22967479
TI  - Improved ethanol yield and reduced minimum ethanol selling price (MESP) by
      modifying low severity dilute acid pretreatment with deacetylation and mechanical
      refining: 2) Techno-economic analysis.
AB  - BACKGROUND: Our companion paper discussed the yield benefits achieved by
      integrating deacetylation, mechanical refining, and washing with low acid and low
      temperature pretreatment. To evaluate the impact of the modified process on the
      economic feasibility, a techno-economic analysis (TEA) was performed based on the
      experimental data presented in the companion paper. RESULTS: The cost benefits of
      dilute acid pretreatment technology combined with the process alternatives of
      deacetylation, mechanical refining, and pretreated solids washing were evaluated
      using cost benefit analysis within a conceptual modeling framework. Control cases
      were pretreated at much lower acid loadings and temperatures than used those in
      the NREL 2011 design case, resulting in much lower annual ethanol production.
      Therefore, the minimum ethanol selling prices (MESP) of the control cases were
      $0.41-$0.77 higher than the $2.15/gallon MESP of the design case. This increment
      is highly dependent on the carbohydrate content in the corn stover. However, if
      pretreatment was employed with either deacetylation or mechanical refining, the
      MESPs were reduced by $0.23-$0.30/gallon. Combing both steps could lower the MESP
      further by $0.44 ~ $0.54. Washing of the pretreated solids could also greatly
      improve the final ethanol yields. However, the large capital cost of the solid
      liquid separation unit negatively influences the process economics. Finally,
      sensitivity analysis was performed to study the effect of the cost of the
      pretreatment reactor and the energy input for mechanical refining. A 50% cost
      reduction in the pretreatment reactor cost reduced the MESP of the entire
      conversion process by $0.11-$0.14/gallon, while a 10-fold increase in energy
      input for mechanical refining will increase the MESP by $0.07/gallon. CONCLUSION:
      Deacetylation and mechanical refining process options combined with low acid, low
      severity pretreatments show improvements in ethanol yields and calculated MESP
      for cellulosic ethanol production.

PMID- 22967480
TI  - Neuroprotective and anti-ageing role of leptin.
AB  - Leptin (Lep), an adipose-derived hormone, exerts very important functions in the
      body mainly on energy storage and availability. The physiological effects of Lep
      controlling the body weight and suppressing appetite are mediated by the long
      form of Lep receptor in the hypothalamus. Lep receptor activates several
      downstream molecules involved in key pathways related to cell survival such as
      STAT3, PI3K, MAPK, AMPK, CDK5 and GSK3beta. Collectively, these pathways act in a
      coordinated manner and form a network that is fully involved in Lep physiological
      response. Although the major interest in Lep is related to its role in the
      regulation of energy balance, and since resistance to Lep affects is the primary
      risk factor for obesity, the interest on their effects on brain cognition and
      neuroprotection is increasing. Thus, Lep and Lep mimetic compounds now await and
      deserve systematic exploration as the orchestrator of protective responses in the
      nervous system. Moreover, Lep might promote the activation of a cognitive process
      that may retard or even partially reverse selected aspects of Alzheimer's disease
      or ageing memory loss.

PMID- 22967481
TI  - The progesterone-responsive gene 14-3-3tau enhances the transcriptional activity
      of progesterone receptor in uterine cells.
AB  - Members of the 14-3-3 family are intracellular dimeric phosphoserine-binding
      proteins that can associate with and modulate the activities of many proteins. In
      our efforts to isolate the genes regulated by progesterone (P(4)) using
      suppressive subtractive hybridization, we previously found that 14-3-3tau is one
      of the genes upregulated by P(4). In this study, we demonstrated by quantitative
      RT-PCR (qRT-PCR), western blot analyses, and immunohistochemistry that 14-3-3tau
      mRNA and protein levels were increased in the rat uterus after P(4) treatment.
      Furthermore, qRT-PCR indicated that P(4) increased 14-3-3tau mRNA levels in human
      endometrial epithelial cells and endometrial stromal cells (ESCs). Western blot
      and qRT-PCR analyses revealed that in vitro decidualization using cAMP and
      medroxyprogesterone 17-acetate increased levels of 14-3-3tau mRNA and protein in
      ESCs. We have shown by qRT-PCR and western blot analyses that P(4) increased the
      mRNA and protein levels of 14-3-3tau in Ishikawa cells that stably express P(4)
      receptor-B (PR-B). Immunocytochemistry revealed that 14-3-3tau colocalizes with
      PR and translocates from the cytoplasm to the nucleus in response to P(4).
      Moreover, by luciferase reporter assay, we demonstrated that 14-3-3tau enhances
      the transcriptional activity of PR-B. Taken together, we propose that 14-3-3tau
      is a P(4)-responsive gene in uterine cells that modulates P(4) signaling.

PMID- 22967484
TI  - Surgical training models: a new vision. Broad-based general surgery and rural
      general surgery training.

PMID- 22967485
TI  - Clinical trials with endothelin receptor antagonists: what went wrong and where
      can we improve?
AB  - In the early 1990s, within three years of cloning of endothelin receptors, orally
      active endothelin receptor antagonists (ERAs) were tested in humans and the first
      clinical trial of ERA therapy in humans was published in 1995. ERAs were
      subsequently tested in clinical trials involving heart failure, pulmonary
      arterial hypertension, resistant arterial hypertension, stroke/subarachnoid
      hemorrhage and various forms of cancer. The results of most of these trials -
      except those for pulmonary arterial hypertension and scleroderma-related digital
      ulcers - were either negative or neutral. Problems with study design, patient
      selection, drug toxicity, and drug dosing have been used to explain or excuse
      failures. Currently, a number of pharmaceutical companies who had developed ERAs
      as drug candidates have discontinued clinical trials or further drug development.
      Given the problems with using ERAs in clinical medicine, at the Twelfth
      International Conference on Endothelin in Cambridge, UK, a panel discussion was
      held by clinicians actively involved in clinical development of ERA therapy in
      renal disease, systemic and pulmonary arterial hypertension, heart failure, and
      cancer. This article provides summaries from the panel discussion as well as
      personal perspectives of the panelists on how to proceed with further clinical
      testing of ERAs and guidance for researchers and decision makers in clinical drug
      development on where future research efforts might best be focused.

PMID- 22967487
TI  - Small-scale purification and mass spectrometry analysis reveal a third aquaporin
      4 protein isoform of 36 kDa in rat brain.
AB  - Aquaporin-4 (AQP4) is known to have two main isoforms M1 and M23 in the brain.
      Immunoblot analyses have provided evidence of additional AQP4 immunopositive
      bands, suggesting that the repertoire of AQP4 isoforms is broader than previously
      assumed. As isoforms beyond M1 and M23 are not observed in recombinant systems,
      investigation of novel isoforms requires the use of a native source. Here we
      report purification of AQP4 to three silver-stained proteins on SDS-PAGE. This
      was achieved by organelle separation, alkaline stripping of cellular membranes,
      detergent solubilization and multiple chromatographic steps. The three proteins
      that co-purified were identified as AQP4 by mass spectrometry. These results
      represent the first purification of AQP4 from a native source and demonstrate by
      mass spectrometry the presence of a third AQP4 isoform of 36 kDa in the rat
      brain. Immunoblots revealed that the same isoform is present in the mouse, pig,
      and human brain.

PMID- 22967486
TI  - Screen of FDA-approved drug library reveals compounds that protect hair cells
      from aminoglycosides and cisplatin.
AB  - Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss
      and balance disorders. Several beneficial pharmaceutical drugs cause hair cell
      death as a side effect. These include aminoglycoside antibiotics, such as
      neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such
      as cisplatin. Discovering new compounds that protect mammalian hair cells from
      toxic insults is experimentally difficult because of the inaccessibility of the
      inner ear. We used the zebrafish lateral line sensory system as an in vivo
      screening platform to survey a library of FDA-approved pharmaceuticals for
      compounds that protect hair cells from neomycin, gentamicin, kanamycin and
      cisplatin. Ten compounds were identified that provide protection from at least
      two of the four toxins. The resulting compounds fall into several drug classes,
      including serotonin and dopamine-modulating drugs, adrenergic receptor ligands,
      and estrogen receptor modulators. The protective compounds show different effects
      against the different toxins, supporting the idea that each toxin causes hair
      cell death by distinct, but partially overlapping, mechanisms. Furthermore, some
      compounds from the same drug classes had different protective properties,
      suggesting that they might not prevent hair cell death by their known target
      mechanisms. Some protective compounds blocked gentamicin uptake into hair cells,
      suggesting that they may block mechanotransduction or other routes of entry. The
      protective compounds identified in our screen will provide a starting point for
      studies in mammals as well as further research discovering the cellular signaling
      pathways that trigger hair cell death.

PMID- 22967488
TI  - Evaluation of transcranial Doppler flow velocity changes in intracerebral
      hemorrhage rats using ultrasonography.
AB  - This study investigated the blood flow velocity changes in seven major arteries
      in rat brain before and after intracerebral hemorrhage (ICH) using high frequency
      transcranial Doppler (TCD) ultrasonography (13-4 MHz). Eighteen adult Sprague
      Dawley rats received either the collagenase-injection surgery (ICH, n=12) or the
      saline-injection surgery (control, n=6) after baseline TCD flow velocity values
      were recorded. The TCD flow velocity changes were measured at 0.5h after the
      surgery and daily for the following 8 days in seven major cerebral arteries,
      including bilateral internal carotid arteries, bilateral middle cerebral arteries
      (MCAs), bilateral posterior cerebral arteries (PCAs), and basilar artery. The
      results showed a significant decrease of TCD flow velocity in the right MCA at
      0.5 h and 24 h after the collagenase-injection surgery, and in the right PCA at
      0.5 h in the ICH group rats. The TCD flow velocities in these two arteries
      gradually increased and then returned to the baseline values in the following
      days. The control group rats did not show significant changes in TCD flow
      velocity in all monitored arteries. This study demonstrates the feasibility and
      reliability of monitoring TCD flow velocity in cerebral arteries using
      ultrasonography technique in a rat ICH model. The results of this study extend
      our knowledge in the cerebrovascular changes during intracranial hemorrhage and
      suggest a possibility of clinical application of TCD ultrasonography in studying
      the dynamic cerebral circulation after strokes. Moreover, this method could be
      extensively applied in further studies using potential neuroprotective treatments
      that affect the cerebral dynamics in the intracerebral hemorrhage.

PMID- 22967489
TI  - Metal-enhanced upconversion luminescence tunable through metal nanoparticle
      nanophosphor separation.
AB  - We have demonstrated amplification of luminescence in upconversion nanophosphors
      (UCNPs) of hexagonal phase NaYF(4) (beta-NaYF(4)) doped with the lanthanide
      dopants Yb(3+), Er(3+) or Yb(3+), Tm(3+) by close proximity to metal
      nanoparticles (NPs). We present a configuration in which close-packed monolayers
      of UCNPs are separated from a dense multilayer of metal NPs (Au or Ag) by a
      nanometer-scale oxide grown by atomic layer deposition. Luminescence enhancements
      were found to be dependent on the thickness of the oxide spacer layer and the
      type of metal NP with enhancements of up to 5.2-fold proximal to Au NPs and of up
      to 45-fold proximal to Ag NPs. Concomitant shortening of the UCNP luminescence
      decay time and rise time is indicative of the enhancement of the UCNP
      luminescence induced by resonant plasmonic coupling and nonresonant near-field
      enhancement from the metal NP layer, respectively.

PMID- 22967490
TI  - A docetaxel-carboxymethylcellulose nanoparticle outperforms the approved taxane
      nanoformulation, Abraxane, in mouse tumor models with significant control of
      metastases.
AB  - Cellax is a PEGylated carboxymethylcellulose conjugate of docetaxel (DTX) which
      condenses into a 120-nm nanoparticle, and was compared against the approved
      clinical taxane nanoformulation (Abraxane(r)) in mouse models. Cellax increased
      the systemic exposure of taxanes by 37* compared to Abraxane, and improved the
      delivery specificity: Cellax uptake was selective to the tumor, liver and spleen,
      with a 203* increase in tumor accumulation compared to Abraxane. The
      concentration of released DTX in Cellax treated tumors was well above the IC50
      for at least 10 d, while paclitaxel released from Abraxane was undetectable after
      24h. In s.c. PC3 (prostate) and B16F10 (melanoma) models, Cellax exhibited
      enhanced efficacy and was better tolerated compared to Abraxane. In an orthotopic
      4T1 breast tumor model, Cellax reduced the incidence of lung metastasis to 40%
      with no metastasic incidence in other tissues. Mice treated with Abraxane
      displayed increased lung metastasic incidence (>85%) with metastases detected in
      the bone, liver, spleen and kidney. These results confirm that Cellax is a more
      effective drug delivery strategy compared to the approved taxane nanomedicine.

PMID- 22967491
TI  - A simple method to derive speed for the endurance shuttle walk test.
AB  - BACKGROUND: The original method for determining endurance shuttle walk test
      (ESWT) speed involves components that are time consuming for clinicians. We
      sought to determine: (i) whether components described in the original method for
      determining ESWT speed held true and; (ii) the agreement between speeds derived
      using the original method and that equivalent to 85% of the peak speed achieved
      during the incremental shuttle walk test (ISWT). METHODS: Patients with chronic
      obstructive pulmonary disease (COPD) performed two ISWTs and one ESWT on separate
      days, wearing a calibrated portable gas analysis unit. A retrospective analysis
      of these data allowed us to determine whether: (i) the peak rate of oxygen uptake
      (VO2peak) can be accurately estimated from the incremental shuttle walk distance
      (ISWD) and; (ii) ESWTs performed at a speed derived using the original method
      elicited 85% of VO2peak. Agreement between walks speeds was determined using
      Bland-Altman analysis. RESULTS: Twenty-two participants (FEV1 48 +/- 13%
      predicted, age 66 +/- 8 yr) completed the study. The VO2peak estimated from the
      ISWD was less than that measured during the ISWT (mean difference -4.4; 95%
      confidence interval (CI), -6.0 to -2.9 ml. kg-1.min-1). The ESWT and ISWT
      elicited similar VO2peak (mean difference -0.2; 95% CI, -1.5 to 1.2 ml.kg-1.min
      1). The mean difference (+/-limits of agreement) between ESWT speeds was 0.15 (+/
      0.34) km.h-1. CONCLUSIONS: Components of the original method for determining the
      ESWT speed did not hold true in our sample. ESWT speed can be derived by
      calculating 85% of the peak speed achieved during the ISWT.

PMID- 22967492
TI  - Fertilizer induced nitrous oxide emissions from Vertisols and Alfisols during
      sweet sorghum cultivation in the Indian semi-arid tropics.
AB  - Nitrous oxide (N(2)O) emissions from Vertisols and Alfisols during sweet sorghum
      cultivation in the Indian semi-arid tropics were determined using a closed
      chamber technique during the rainy season (June-October) of 2010. The study
      included two treatments, nitrogen (N) at a rate of 90 kg/ha and a control without
      N fertilizer application. The N(2)O emissions strongly coincided with N
      fertilization and rainfall events. The cumulative N(2)O-N emission from Alfisols
      was 1.81 N(2)O-N kg/ha for 90 N treatment and 0.15 N(2)O-N kg/ha for the 0 N
      treatment. Similarly, the N(2)O-N emission from Vertisols was 0.70 N(2)O-N kg/ha
      for 90 N treatment and 0.09 N(2)O-N kg/ha for the 0 N treatment. The mean N(2)O-N
      emission factor for fertilizer induced emissions from the Alfisols was 0.90% as
      compared to 0.32% for Vertisols. Our results suggest that the N(2)O emissions are
      dependent on the soil properties. Therefore, the monitoring of N(2)O emissions
      from different agro-ecological regions, having different soil types, rainfall
      characteristics, cropping systems and crop management practices are necessary to
      develop comprehensive and accurate green house gas inventories.

PMID- 22967493
TI  - Monitoring release of pharmaceutical compounds: occurrence and environmental risk
      assessment of two WWTP effluents and their receiving bodies in the Po Valley,
      Italy.
AB  - This study describes an investigation on the occurrence of 27 pharmaceutical
      compounds, belonging to different classes, in the effluent from two wastewater
      treatment plants (WWTPs) and their receiving water bodies in the sensitive area
      of the Po Valley (northern Italy). These canals were monitored upstream and
      downstream of the effluent discharge points in order to evaluate the effluent
      impact on the quality of surface waters, commonly used for irrigation. An
      environmental risk assessment was also conducted by calculating the risk
      quotient, i.e. the ratio between measured concentration and predicted no effect
      concentration. Collected data show that, although average values of the selected
      compounds were in general higher in the effluent than in the surface waters, some
      compounds not detected in the WWTP effluent were detected in the receiving water
      (upstream as well as downstream), indicating that sources other than treated
      effluents are present as contaminations during extraction and analysis have to be
      excluded. The most critical compounds for the environment were found to be the
      antibiotics sulfamethoxazole, clarithromycin and azithromycin. The study shows
      that the potential toxicological effects of persistent micropollutants can be
      mitigated to some extent by a high dilution capacity, i.e. a high average flow
      rate in the receiving water body with respect to the effluent.

PMID- 22967494
TI  - Adsorption of norfloxacin onto titanium oxide: effect of drug carrier and
      dissolved humic acid.
AB  - Titanium dioxide is widely used as an effective catalyst in wastewater treatment.
      The effects of drug carriers (cyclodextrins, 100MUM) or dissolved humic acids (0
      50mg/L) or pH (3.0-11.0) on adsorption of norfloxacin to two TiO(2) (Hombikat UV
      100 and Anatase TiO(2)) surfaces were systematically studied. Norfloxacin shows
      high adsorption affinity to TiO(2) surface. Specific surface area of TiO(2) shows
      great influence on norfloxacin adsorption especially in acidic solutions. The
      effect of pH on norfloxacin adsorption originates from the changes of TiO(2)'s
      surface charge and speciation of norfloxacin. The presence of humic acids
      (50mg/L) suppresses the adsorption of norfloxacin onto Hombikat UV-100 and
      Anatase TiO(2) prominently. The co-effect of heptakis(2,6-di-O-methyl)-beta
      cyclodextrin (methyl-beta-CD) and humic acid is similar to the solo effect of
      humic acid on the adsorption of norfloxacin onto Hombikat UV-100, while the co
      effect shows a more retardation effect on the adsorption of norfloxacin onto
      Anatase TiO(2). Humic acid and beta-CD show a synergetic depressed effect on the
      adsorption of norfloxacin onto both TiO(2) surfaces. These results show that both
      aquatic solution chemistry and drug carrier are important to norfloxacin
      adsorption on TiO(2), which could alter the environmental fate and transport of
      norfloxacin.

PMID- 22967495
TI  - Environmental fate model for ultra-low-volume insecticide applications used for 
      adult mosquito management.
AB  - One of the more effective ways of managing high densities of adult mosquitoes
      that vector human and animal pathogens is ultra-low-volume (ULV) aerosol
      applications of insecticides. The U.S. Environmental Protection Agency uses
      models that are not validated for ULV insecticide applications and exposure
      assumptions to perform their human and ecological risk assessments. Currently,
      there is no validated model that can accurately predict deposition of
      insecticides applied using ULV technology for adult mosquito management. In
      addition, little is known about the deposition and drift of small droplets like
      those used under conditions encountered during ULV applications. The objective of
      this study was to perform field studies to measure environmental concentrations
      of insecticides and to develop a validated model to predict the deposition of ULV
      insecticides. The final regression model was selected by minimizing the Bayesian
      Information Criterion and its prediction performance was evaluated using k-fold
      cross validation. Density of the formulation and the density and CMD interaction
      coefficients were the largest in the model. The results showed that as density of
      the formulation decreases, deposition increases. The interaction of density and
      CMD showed that higher density formulations and larger droplets resulted in
      greater deposition. These results are supported by the aerosol physics
      literature. A k-fold cross validation demonstrated that the mean square error of
      the selected regression model is not biased, and the mean square error and mean
      square prediction error indicated good predictive ability.

PMID- 22967496
TI  - Identification and quantification of newly synthesized proteins translationally
      regulated by YB-1 using a novel Click-SILAC approach.
AB  - Messenger RNA-binding translational regulatory proteins determine in large part
      the spectrum of transcripts that are translated under specific cellular contexts.
      Y-box binding protein-1 (YB-1) is a conserved eukaryotic translational regulator
      that is implicated in cancer progression. To identify specific proteins that are
      translationally regulated by YB-1, we established a pulse-labelling approach
      combining Click chemistry and stable isotope labelling by amino acids in cell
      culture (SILAC). The proteome of TC32 human Ewing sarcoma cells, which robustly
      express YB-1, was compared with or without YB-1 siRNA knockdown. Cells labelled
      with light or heavy isotopologs of Arg and Lys were then cotranslationally pulsed
      with the methionine derivative, azidohomoalanine (AHA). Cells were lysed and
      newly synthesized proteins were selectively derivatized via a Click (3+2
      cycloaddition) reaction to add an alkyne biotin tag. They were then affinity
      purified and subjected to liquid chromatography-tandem mass spectrometry. This
      combined Click-SILAC approach enabled us to catalog and quantify newly
      synthesized proteins regulated by YB-1 after only 45 min of labelling.
      Bioinformatic analysis revealed that YB-1 regulated proteins are involved in
      diverse biological pathways. We anticipate that this Click-SILAC strategy will be
      useful for studying short-term protein synthesis in different cell culture
      systems and under diverse biological contexts.

PMID- 22967497
TI  - Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial
      fibrillation--a protocol of a single center, randomized, double-blind, placebo
      controlled study (the AnPAF Study).
AB  - BACKGROUND: Rapid conversion of atrial fibrillation (AF) to sinus rhythm may be
      achieved by the administration of class IA, IC and III antiarrhythmic drugs or
      vernakalant hydrochloride. However, that treatment may be related to potential
      pro-arrhythmia, lack of efficacy or the exceptionally high cost of a compound
      used. Antazoline is a first generation antihistaminic agent with chinidin-like
      properties. When administered intravenously, antazoline exerts a strong
      antiarrhythmic effect on supraventricular arrhythmia, especially on AF,
      facilitating rapid conversion to sinus rhythm. Despite a relative lack of
      published data antazoline has been marketed in Poland and widely used in
      cardiology wards and emergency rooms for many years due to its efficacy, safety
      and rapid onset of action within minutes of administration. METHODS/DESIGN: A
      randomized, double blind, placebo-controlled, superiority clinical trial was
      designed to assess clinical efficacy of antazoline in rapid conversion of AF to
      sinus rhythm. Eligible patients will present AF lasting less than 43 hours, will
      be in stable cardio-pulmonary condition and will have no prior history of
      advanced heart failure or significant valvular disease. Long-term antiarrhythmic
      therapy is not considered an exclusion criterion. Subjects who fulfill selection
      criteria will be randomly assigned to receive intravenously either antazoline or
      placebo in divided doses and observed for 1.5 hours after conversion to sinus
      rhythm or after the last i.v. bolus. Primary end point will be the conversion of
      AF to sinus rhythm confirmed in an electrocardiogram (ECG) during the observation
      period. Secondary end points will be comprised of time to conversion and return
      of AF during the observation period. Special consideration will be given to the
      observation of any adverse events. A sample size of 80 patients was calculated
      based on the following assumptions: two-tailed test, a type I error of 0.01, a
      power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out
      rate to fulfill the criteria of intention-to-treat analysis. Due to the presumed
      lack of statistical power, the secondary end points and safety endpoints will be
      considered exploratory. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov,
      NCT01527279.

PMID- 22967498
TI  - PET imaging reveals distinctive roles for different regional adipose tissue
      depots in systemic glucose metabolism in nonobese humans.
AB  - Excess amounts of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue
      (AT) are associated with insulin resistance, even in normal-weight subjects. In
      contrast, gluteal-femoral AT (GFAT) is hypothesized to offer protection against
      insulin resistance. Dynamic PET imaging studies were undertaken to examine the
      contributions of both metabolic activity and size (volume) of these depots in
      systemic glucose metabolism. Nonobese, healthy volunteers (n = 15) underwent
      dynamic PET imaging uptake of [18F]FDG at a steady-state (20 mU.m-2.min-1)
      insulin infusion. PET images of tissue [18F]FDG activity were coregistered with
      MRI to derive K values for insulin-stimulated rates of fractional glucose uptake
      within tissue. Adipose tissue volume was calculated from DEXA and MRI. VAT had
      significantly higher rates of fractional glucose uptake per volume than SAT (P <
      0.05) or GFAT (P < 0.01). K(GFAT) correlated positively (r = 0.67, P < 0.01) with
      systemic insulin sensitivity [glucose disappearance rate (R(d))] and negatively
      with insulin-suppressed FFA (r = -0.71, P < 0.01). SAT (r = -0.70, P < 0.01) and
      VAT mass (r = -0.55, P < 0.05) correlated negatively with R(d), but GFAT mass did
      not. We conclude that rates of fractional glucose uptake within GFAT and VAT are
      significantly and positively associated with systemic insulin sensitivity in
      nonobese subjects. Furthermore, whereas SAT and VAT amounts are confirmed to
      relate to systemic insulin resistance, GFAT amount is not associated with insulin
      resistance. These dynamic PET imaging studies indicate that both quantity and
      quality of specific AT depots have distinct roles in systemic insulin resistance
      and may help explain the metabolically obese but normal-weight phenotype.

PMID- 22967499
TI  - Leucine supplementation increases SIRT1 expression and prevents mitochondrial
      dysfunction and metabolic disorders in high-fat diet-induced obese mice.
AB  - Leucine supplementation has been shown to prevent high-fat diet (HFD)-induced
      obesity, hyperglycemia, and dyslipidemia in animal models, but the underlying
      mechanisms are not fully understood. Recent studies suggest that activation of
      Sirtuin 1 (SIRT1) is an important mechanism to maintain energy and metabolic
      homeostasis. We therefore examined the involvement of SIRT1 in leucine
      supplementation-prevented obesity and insulin resistance. To accomplish this
      goal, male C57BL/6J mice were fed normal diet or HFD, supplemented with or
      without leucine. After 2 mo of treatment, alterations in SIRT1 expression,
      insulin signaling, and energy metabolism were analyzed. Eight weeks of HFD
      induced obesity, fatty liver, mitochondrial dysfunction, hyperglycemia, and
      insulin resistance in mice. Addition of leucine to HFD correlated with increased
      expression of SIRT1 and NAMPT (nicotinamide phosphoribosyltransferase) as well as
      higher intracellular NAD(+) levels, which decreased acetylation of peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) and forkhead
      box O1 (FoxO1). The deacetylation of PGC1alpha may contribute to upregulation of
      genes controlling mitochondrial biogenesis and fatty acid oxidation, thereby
      improving mitochondrial function and preventing HFD-induced obesity in mice.
      Moreover, decreased acetylation of FoxO1 was accompanied by decreased expression
      of pseudokinase tribble 3 (TRB3) and reduced the association between TRB3 and
      Akt, which enhanced insulin sensitivity and improved glucose metabolism. Finally,
      transfection of dominant negative AMPK prevented activation of SIRT1 signaling in
      HFD-Leu mice. These data suggest that increased expression of SIRT1 after leucine
      supplementation may lead to reduced acetylation of PGC1alpha and FoxO1, which is
      associated with attenuation of HFD-induced mitochondrial dysfunction, insulin
      resistance, and obesity.

PMID- 22967500
TI  - Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis,
      and ATP production in human skeletal muscle without amino acid replacement.
AB  - Systemic insulin administration causes hypoaminoacidemia by inhibiting protein
      degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin
      enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is
      prevented by exogenous amino acid (AA) replacement. We determined whether insulin
      would stimulate mitochondrial PS and ATP production in the absence of AA
      replacement. Using l-[1,2-13C]leucine as a tracer, we measured the fractional
      synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins
      in 18 participants during sustained (7-h) insulin or saline infusion (n = 9
      each). We also measured muscle ATP production, mitochondrial enzyme activities,
      mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins
      regulating protein synthesis. The concentration of circulating essential AA
      decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle
      PS rates were also lower during insulin (2-7 h) than during saline infusions
      despite increased mRNA levels of selected mitochondrial genes. Under these
      conditions, insulin did not alter mitochondrial enzyme activities and ATP
      production. These effects were associated with enhanced phosphorylation of Akt
      but not of protein synthesis activators mTOR, p70(S6K), and 4EBP1. In conclusion,
      sustained physiological hyperinsulinemia without AA replacement did not stimulate
      PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial
      ATP production in healthy humans. These results support that insulin and AA act
      in conjunction to stimulate muscle mitochondrial function and mitochondrial
      protein synthesis.

PMID- 22967501
TI  - Responses of skeletal muscle lipid metabolism in rat gastrocnemius to
      hypothyroidism and iodothyronine administration: a putative role for FAT/CD36.
AB  - Iodothyronines such as triiodothyronine (T(3)) and 3,5-diiodothyronine (T(2))
      influence energy expenditure and lipid metabolism. Skeletal muscle contributes
      significantly to energy homeostasis, and the above iodothyronines are known to
      act on this tissue. However, little is known about the cellular/molecular events
      underlying the effects of T(3) and T(2) on skeletal muscle lipid handling. Since
      FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle,
      specifically in their import into that tissue and presumably their oxidation at
      the mitochondrial level, we hypothesized that related changes in lipid handling
      and in FAT/CD36 expression and subcellular redistribution would occur due to
      hypothyroidism and to T(3) or T(2) administration to hypothyroid rats. In
      gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated
      (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels).
      Administration of either T(3) or T(2) to hypothyroid rats resulted in 1) little
      or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level,
      and 3) further increases in FAT/CD36 protein level in sarcolemma and
      mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at
      the level of FAT/CD36 cellular distribution. The effect of further increases in
      FAT/CD36 protein level in sarcolemma and mitochondria was already evident at 1 h
      after iodothyronine administration. Each iodothyronine increased the
      mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their
      rapid effects seem to differ; T(2) and T(3) each induce FAT/CD36 translocation to
      mitochondria, but only T(2) induces increases in carnitine palmitoyl transferase
      system activity and in the mitochondrial substrate oxidation rate.

PMID- 22967502
TI  - The Wnt signaling pathway effector TCF7L2 is upregulated by insulin and represses
      hepatic gluconeogenesis.
AB  - Certain single nucleotide polymorphisms (SNPs) in transcription factor 7-like 2
      (TCF7L2) are strongly associated with the risk of type 2 diabetes. TCF7L2 and
      beta-catenin (beta-cat) form the bipartite transcription factor cat/TCF in
      stimulating Wnt target gene expression. cat/TCF may also mediate the effect of
      other signaling cascades, including that of cAMP and insulin in cell-type
      specific manners. As carriers of TCF7L2 type 2 diabetes risk SNPs demonstrated
      increased hepatic glucose production, we aimed to determine whether TCF7L2
      expression is regulated by nutrient availability and whether TCF7L2 and Wnt
      regulate hepatic gluconeogenesis. We examined hepatic Wnt activity in the TOPGAL
      transgenic mouse, assessed hepatic TCF7L2 expression in mice upon feeding,
      determined the effect of insulin on TCF7L2 expression and beta-cat Ser675
      phosphorylation, and investigated the effect of Wnt activation and TCF7L2
      knockdown on gluconeogenic gene expression and glucose production in hepatocytes.
      Wnt activity was observed in pericentral hepatocytes in the TOPGAL mouse, whereas
      TCF7L2 expression was detected in human and mouse hepatocytes. Insulin and
      feeding stimulated hepatic TCF7L2 expression in vitro and in vivo, respectively.
      In addition, insulin activated beta-cat Ser675 phosphorylation. Wnt activation by
      intraperitoneal lithium injection repressed hepatic gluconeogenic gene expression
      in vivo, whereas lithium or Wnt-3a reduced gluconeogenic gene expression and
      glucose production in hepatic cells in vitro. Small interfering RNA-mediated
      TCF7L2 knockdown increased glucose production and gluconeogenic gene expression
      in cultured hepatocytes. These observations suggest that Wnt signaling and TCF7L2
      are negative regulators of hepatic gluconeogenesis, and TCF7L2 is among the
      downstream effectors of insulin in hepatocytes.

PMID- 22967503
TI  - Optimising vitrification of human oocytes using multiple cryoprotectants and
      morphological and functional assessment.
AB  - Oocyte vitrification is a clinical practice that allows preservation of fertility
      potential in women. Vitrification involves quick cooling using high
      concentrations of cryoprotectants to minimise freezing injuries. However, high
      concentrations of cryoprotectants have detrimental effects on oocyte quality and
      eventually the offspring. In addition, current assessment of oocyte quality after
      vitrification is commonly based only on the morphological appearance of the
      oocyte, raising concerns regarding its efficiency. Using both morphological and
      functional assessments, the present study investigated whether combinations of
      cryoprotectants at lower individual concentrations result in better cryosurvival
      rates than single cryoprotectants at higher concentrations. Surplus oocytes from
      IVF patients were vitrified within 24h after retrieval using the Cryotop method
      with several cryoprotectants, either individually or in combination. The
      morphological and functional quality of the vitrified oocytes was investigated
      using light microscopy and computer-based quantification of mitochondrial
      integrity, respectively. Oocyte quality was significantly higher using a
      combination of cryoprotectants than vitrification with individual
      cryoprotectants. In addition, the quality of vitrified oocyte varied depending on
      the cryoprotectants and type of combination used. The results of the present
      study indicate that observations based purely on the morphological appearance of
      the oocyte to assess the cryosurvival rate are insufficient and sometimes
      misleading. The outcome will have a significant implication in the area of human
      oocyte cryopreservation as an important approach for fertility preservation. 

PMID- 22967504
TI  - Interventions in Wnt signaling as a novel therapeutic approach to improve
      myocardial infarct healing.
AB  - Following myocardial infarction, wound healing takes place in the infarct area
      where the non-viable cardiac tissue is replaced by a scar. Inadequate wound
      healing or insufficient maintenance of the extracellular matrix in the scar can
      lead to excessive dilatation of the ventricles, one of the hallmarks of
      congestive heart failure. Therefore, it is important to better understand the
      wound-healing process in the heart and to develop new therapeutic agents that
      target the infarct area in order to maintain an adequate cardiac function. One of
      these potential novel therapeutic targets is Wnt signaling. Wnt signaling plays
      an important role in embryonic myocardial development but in the adult heart the
      pathway is thought to be silent. However, there is increasing evidence that
      components of the Wnt pathway are re-expressed during cardiac repair, implying a
      regulatory role. Recently, several studies have been published where the effect
      of interventions in Wnt signaling on infarct healing has been studied. In this
      review, we will summarize the results of these studies and discuss the effects of
      these interventions on the different cell types that are involved in the wound
      healing process.

PMID- 22967505
TI  - Trajectories of combined laboratory- and real world-based speed of processing in
      community-dwelling older adults.
AB  - OBJECTIVES: To characterize the trajectories of laboratory- and real world-based
      speed of processing (SOP) over 5 years using finite latent growth mixture
      modeling, and to explore associated baseline individual-level predictors and
      functional outcomes in 2,802 community-dwelling older adults from the Advanced
      Cognitive Training for Independent and Vital Elderly cohort. METHOD: Laboratory-
      and real world-based SOP and functional outcomes were assessed over 5 years, and
      candidate individual-level predictors were collected at baseline. RESULTS: After
      controlling for intervention assignment and demographic information, 4 distinct
      trajectories were identified: 4.6% of older adults had poor laboratory-based SOP
      and very poor real world-based SOP that both declined substantially over time;
      17.9% had poor laboratory- and real world-based SOP that declined moderately;
      38.7% had neutral laboratory- and real world-based SOP that maintained stable;
      and 37.9% had good laboratory- and real world-based SOP that declined slightly.
      Non-White, depression, subjective memory complaints, and vascular factors
      predicted the trajectories. The trajectories significantly differed in the rate
      of decline in basic activities of daily living, instrumental activities of daily
      living, and grip strength over time. DISCUSSION: Heterogeneous trajectories of
      SOP exist in old age. Future interventions addressing SOP should target the
      vulnerable group with poor SOP over time.

PMID- 22967506
TI  - Who knows who is wise? Self and peer ratings of wisdom.
AB  - OBJECTIVES: This study investigated relationships between three measures of
      wisdom: self-ratings, peer ratings, and a self-report scale. We expected to find
      a zero or negative correlation between the self-rating and the average peer
      rating and low positive correlations of both to the self-report scale. We also
      tested whether there would be more convergence among measures in the top scorers.
      METHOD: A total of 179 members of 17 university departments were rated by their
      department colleagues with respect to wisdom; about half of them also rated
      themselves and filled out a wisdom self-report scale (Three-Dimensional Wisdom
      Scale [3D-WS]; Ardelt, M. (2003)). RESULTS: There were no significant
      relationships among the three measures of wisdom, neither in the total sample nor
      among the top scorers. DISCUSSION: Depending on the focus of research, peer
      ratings may be a more suitable measure of wisdom than self-report scales or
      performance measures.

PMID- 22967507
TI  - Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines
      their toxicity.
AB  - Neurodegenerative diseases constitute a class of illnesses marked by pathological
      protein aggregation in the brains of affected individuals. Although these
      disorders are invariably characterized by the degeneration of highly specific
      subpopulations of neurons, protein aggregation occurs in all cells, which
      indicates that toxicity arises only in particular cell biological contexts.
      Aggregation-associated disorders are unified by a common cell biological feature:
      the deposition of the culprit proteins in inclusion bodies. The precise function
      of these inclusions remains unclear. The starting point for uncovering the
      origins of disease pathology must therefore be a thorough understanding of the
      general cell biological function of inclusions and their potential role in
      modulating the consequences of aggregation. Here, we show that in human cells
      certain aggregate inclusions are active compartments. We find that toxic
      aggregates localize to one of these compartments, the juxtanuclear quality
      control compartment (JUNQ), and interfere with its quality control function. The
      accumulation of SOD1G93A aggregates sequesters Hsp70, preventing the delivery of
      misfolded proteins to the proteasome. Preventing the accumulation of SOD1G93A in
      the JUNQ by enhancing its sequestration in an insoluble inclusion reduces the
      harmful effects of aggregation on cell viability.

PMID- 22967508
TI  - Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and
      metastasis.
AB  - Interplay between various lymphangiogenic factors in promoting lymphangiogenesis
      and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and
      VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and
      lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary
      and lymph-node metastases. Coimplantation of dual factors in the mouse cornea
      resulted in additive angiogenesis and lymphangiogenesis. At the molecular level,
      we showed that FGFR-1 expressed in lymphatic endothelial cells is a crucial
      receptor that mediates the FGF-2-induced lymphangiogenesis. Intriguingly, the
      VEGFR-3-mediated signaling was required for the lymphatic tip cell formation in
      both FGF-2- and VEGF-C-induced lymphangiogenesis. Consequently, a VEGFR-3
      specific neutralizing antibody markedly inhibited FGF-2-induced
      lymphangiogenesis. Thus, the VEGFR-3-induced lymphatic endothelial cell tip cell
      formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor
      microenvironment, the reciprocal interplay between FGF-2 and VEGF-C
      collaboratively stimulated tumor growth, angiogenesis, intratumoral
      lymphangiogenesis, and metastasis. Thus, intervention and targeting of the FGF-2-
      and VEGF-C-induced angiogenic and lymphangiogenic synergism could be potentially
      important approaches for cancer therapy and prevention of metastasis.

PMID- 22967509
TI  - Microbial oceanography of anoxic oxygen minimum zones.
AB  - Vast expanses of oxygen-deficient and nitrite-rich water define the major oxygen
      minimum zones (OMZs) of the global ocean. They support diverse microbial
      communities that influence the nitrogen economy of the oceans, contributing to
      major losses of fixed nitrogen as dinitrogen (N(2)) and nitrous oxide (N(2)O)
      gases. Anaerobic microbial processes, including the two pathways of N(2)
      production, denitrification and anaerobic ammonium oxidation, are oxygen
      sensitive, with some occurring only under strictly anoxic conditions. The
      detection limit of the usual method (Winkler titrations) for measuring dissolved
      oxygen in seawater, however, is much too high to distinguish low oxygen
      conditions from true anoxia. However, new analytical technologies are revealing
      vanishingly low oxygen concentrations in nitrite-rich OMZs, indicating that these
      OMZs are essentially anoxic marine zones (AMZs). Autonomous monitoring platforms
      also reveal previously unrecognized episodic intrusions of oxygen into the AMZ
      core, which could periodically support aerobic metabolisms in a typically anoxic
      environment. Although nitrogen cycling is considered to dominate the microbial
      ecology and biogeochemistry of AMZs, recent environmental genomics and
      geochemical studies show the presence of other relevant processes, particularly
      those associated with the sulfur and carbon cycles. AMZs correspond to an
      intermediate state between two "end points" represented by fully oxic systems and
      fully sulfidic systems. Modern and ancient AMZs and sulfidic basins are
      chemically and functionally related. Global change is affecting the magnitude of
      biogeochemical fluxes and ocean chemical inventories, leading to shifts in AMZ
      chemistry and biology that are likely to continue well into the future.

PMID- 22967510
TI  - Rhythmic ring-ring stacking drives the circadian oscillator clockwise.
AB  - The oscillator of the circadian clock of cyanobacteria is composed of three
      proteins, KaiA, KaiB, and KaiC, which together generate a self-sustained ~24-h
      rhythm of phosphorylation of KaiC. The mechanism propelling this oscillator has
      remained elusive, however. We show that stacking interactions between the CI and
      CII rings of KaiC drive the transition from the phosphorylation-specific KaiC
      KaiA interaction to the dephosphorylation-specific KaiC-KaiB interaction. We have
      identified the KaiB-binding site, which is on the CI domain. This site is hidden
      when CI domains are associated as a hexameric ring. However, stacking of the CI
      and CII rings exposes the KaiB-binding site. Because the clock output protein
      SasA also binds to CI and competes with KaiB for binding, ring stacking likely
      regulates clock output. We demonstrate that ADP can expose the KaiB-binding site
      in the absence of ring stacking, providing an explanation for how it can reset
      the clock.

PMID- 22967511
TI  - Silurian horseshoe crab illuminates the evolution of arthropod limbs.
AB  - The basic arrangement of limbs in euarthropods consists of a uniramous head
      appendage followed by a series of biramous appendages. The body is divided into
      functional units or tagmata which are usually distinguished by further
      differentiation of the limbs. The living horseshoe crabs are remnants of a much
      larger diversity of aquatic chelicerates. The limbs of the anterior and posterior
      divisions of the body of living horseshoe crabs differ in the loss of the outer
      and inner ramus, respectively, of an ancestral biramous limb. Here we report a
      new fossil horseshoe crab from the mid-Silurian Lagerstatte in Herefordshire,
      United Kingdom (approximately 425 Myr B.P.), a site that has yielded a remarkably
      preserved assemblage of soft-bodied fossils. The limbs of the new form can be
      homologized with those of living Limulus, but retain an ancestral biramous
      morphology. Remarkably, however, the two limb branches originate separately,
      providing fossil evidence to suggest that repression or loss of gene expression
      might have given rise to the appendage morphology of Limulus. Both branches of
      the prosomal limbs of this new fossil are robust and segmented in contrast to
      their morphology in Cambrian arthropods, revealing that a true biramous limb was
      once present in chelicerates as well as in the mandibulates.

PMID- 22967512
TI  - Parameter-free model discrimination criterion based on steady-state coplanarity.
AB  - We introduce a procedure for deciding when a mass-action model is incompatible
      with observed steady-state data that does not require any parameter estimation.
      Thus, we avoid the difficulties of nonlinear optimization typically associated
      with methods based on parameter fitting. Instead, we borrow ideas from algebraic
      geometry to construct a transformation of the model variables such that any set
      of steady states of the model under that transformation lies on a common plane,
      irrespective of the values of the model parameters. Model rejection can then be
      performed by assessing the degree to which the transformed data deviate from
      coplanarity. We demonstrate our method by applying it to models of multisite
      phosphorylation and cell death signaling. Our framework offers a parameter-free
      perspective on the statistical model selection problem, which can complement
      conventional statistical methods in certain classes of problems where inference
      has to be based on steady-state data and the model structures allow for suitable
      algebraic relationships among the steady-state solutions.

PMID- 22967513
TI  - Regulation and dysregulation of glucose transport in cardiomyocytes.
AB  - The ability of the heart muscle to derive energy from a wide variety of
      substrates provides the myocardium with remarkable capacity to adapt to the ever
      changing metabolic environment depending on factors including nutritional state
      and physical activity. There is increasing evidence that loss of metabolic
      flexibility of the myocardium contributes to cardiac dysfunction in disease
      conditions such as diabetes, ischemic heart disease and heart failure. At the
      level of glucose metabolism reduced metabolic adaptation in most cases is
      characterized by impaired stimulation of transarcolemmal glucose transport in the
      cardiomyocytes in response to insulin, referred to as insulin resistance, or to
      other stimuli such as energy deficiency. This review discusses cellular
      mechanisms involved in the regulation of glucose uptake in cardiomyocytes and
      their potential implication in impairment of stimulation of glucose transport
      under disease conditions. This article is part of a Special Issue entitled:
      Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and
      Contraction.

PMID- 22967514
TI  - An overview of liquid phase microextraction approaches combined with UV-Vis
      spectrophotometry.
AB  - Ultraviolet and visible spectrophotometer has become a popular analytical
      instrument in the modern day laboratories. However, the low concentrations of
      many analytes in samples make it difficult to directly measure them by UV-Vis
      spectrophotometry. This overview focuses on the combinations of microvolume UV
      Vis spectrophotometry with miniaturized approaches to sample preparation, namely,
      single drop microextraction (SDME), dispersive liquid-liquid microextraction
      (DLLME), cold induced aggregation microextraction (CIAME), in situ solvent
      formation microextraction (ISSFME), ultrasound assisted emulsification
      microextraction (USAEME), solidified floating organic drop microextraction
      (SFODME), and hollow fiber based liquid phase microextraction (HF-LPME) to
      improve both the selectivity and sensitivity. Integration of these techniques
      provides unique advantages which include availability, simplicity of operation,
      low cost, speed, precision and accuracy; hence making them a powerful tool in
      chemical analysis.

PMID- 22967515
TI  - Multi-response optimization of magnetic solid phase extraction based on carbon
      coated Fe3O4 nanoparticles using desirability function approach for the
      determination of the organophosphorus pesticides in aquatic samples by HPLC-UV.
AB  - The present study investigates the application of carbon coated Fe(3)O(4)
      (Fe(3)O(4)/C) magnetic nanoparticles as an adsorbent for magnetic solid phase
      extraction (MSPE) of trace amounts of organophosphorus pesticides (OPPs) from
      environmental water samples and their determination using high performance liquid
      chromatography with ultraviolet detection (HPLC-UV). The Fe(3)O(4)/C magnetic
      nanoparticles were synthesized by a simple hydrothermal reaction and the
      resultant material was characterized by X-ray powder diffraction, field emission
      scanning electron microscopy and Fourier transform infrared. Central composite
      design combined with desirability function (DF) was applied to find the
      experimental conditions providing the highest global extraction efficiency. These
      conditions were found in correspondence with a solution pH of 9.16, 97.4 mg
      Fe(3)O(4)/C and 10 mmol L(-1) NaCl added to samples. Under the optimal
      conditions, the proposed method was evaluated, and applied to the analysis of
      OPPs in water samples. The results demonstrated that our proposed method had wide
      dynamic linear range (0.05-400 ng mL(-1)) with a good linearity (R(2)>0.9949) and
      low detection limits (4.3-47.4 pg mL(-1)). High enrichment factors were achieved
      ranging from 330-1200. The established MSPE-HPLC-UV method has been successfully
      applied for the determination of the OPPs in spiked water samples (well, tap,
      river and mineral). Satisfactory recovery results showed that the matrices under
      consideration do not significantly affect the extraction process.

PMID- 22967516
TI  - Mediatorless amperometric glucose biosensing using 3-aminopropyltriethoxysilane
      functionalized graphene.
AB  - A mediatorless glucose biosensor was developed by the immobilization of glucose
      oxidase (GOx) to graphene-functionalized glassy carbon electrode (GCE). The
      surface of GCE was functionalized with graphene by incubating it with graphene
      dispersed in 3-aminopropyltriethoxysilane (APTES), which acted both as a
      dispersion agent for graphene and as an amine surface modification agent for GCE
      and graphene. This was followed by the covalent binding of GOx to graphene
      functionalized GCE using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide
      hydrochloride (EDC) based crosslinking. Graphene provided signal enhancement by
      providing greater surface area for GOx binding, while APTES-functionalization led
      to a higher GOx immobilization density by providing free amino groups for
      crosslinking. The developed biosensor used a redox potential of -0.45 V (vs.
      Ag/AgCl) for detecting glucose in the diabetic pathophysiological range 0.5-32
      mM. There was no interference from endogenous electroactive substances and drug
      metabolites. The developed biosensor was further validated for detecting blood
      glucose in commercial artificial blood glucose linearity standards in the range
      1.4-27.9 mM. Therefore, it is ideal for diabetic blood glucose monitoring. The
      developed bioanalytical procedure for preparation of GOx-bound graphene
      functionalized GCEs had high production reproducibility and high storage
      stability, which is appropriate for the commercial mass production of enzyme
      bound electrodes.

PMID- 22967517
TI  - Pneumatically assisted electrospray-ion mobility spectrometry for quantitative
      analysis of intact proteins.
AB  - In this work, quantitative analysis of intact proteins using ion mobility
      spectrometry (IMS) is introduced. For this purpose a pneumatically assisted
      electrospray ionization source with a new design was constructed. Liquid and
      nebulizer gas flow rates were optimized to achieve the highest response. The
      pneumatically assisted electrospray-IMS was used for quantitative analysis of
      insulin, bovine serum albumin (BSA) and human serum albumin (HSA). The analysis
      of proteins demonstrated that sensitivity of the pneumatically assisted
      electrospray-IMS is two to three times higher than that of conventional
      electrospray ionization (ESI) coupled to IMS. The linear dynamic ranges for
      insulin, BSA and HSA were found to be 1-75, 5-100 and 2-100 MUg mL(-1) with
      detection limits of 0.3, 1 and 0.6 MUg mL(-1), respectively. The relative
      standard deviations (RSD) for five replicate measurements of insulin, BSA, and
      HSA at 25 MUg mL(-1) were recorded as 3, 4 and 1.5%, respectively. The proposed
      method can be considered as an alternative way for quantitative protein analysis.

PMID- 22967518
TI  - A simple strategy to monitor lipase activity using liquid crystal-based sensors.
AB  - In this study, we developed a simple label-free technique for monitoring the
      enzymatic activity of lipase using liquid crystal (LC)-based sensors. The optical
      response of LCs changed from a bright to dark appearance when an aqueous solution
      of lipase was in contact with a nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), that
      was doped with glyceryl trioleate, which is a glyceride that can be enzymatically
      hydrolyzed by lipase. Since the oleic acid released from the enzymatic reaction
      could spontaneously form a self-assembled monolayer at the aqueous/LC interface
      due to its amphiphilic property, the orientation of the LCs transited from a
      planar to homeotropic state, which induced a change in the optical response of
      the LCs. We did not observe a bright-to-dark shift in the optical appearance of
      LCs when pure 5CB was immersed into the lipase solution. Moreover, we further
      confirmed the specificity of the enzymatic reaction by transferring an aqueous
      buffer solution not containing an analyte, or with bovine serum albumin (BSA) or
      trypsin onto the interface of aqueous solutions and the glyceryl trioleate-doped
      5CB, which did not produce any distinctive contrast in the optical appearance.
      These results suggest the feasibility of measuring the enzymatic activity of
      lipase using the LC-based sensing technique. Furthermore, our strategy could also
      be used for the preparation of a self-assembled monolayer of carboxylates at the
      aqueous/LC interface.

PMID- 22967519
TI  - L-histidine functionalized multi-walled carbon nanotubes for on-line affinity
      separation and purification of immunoglobulin G in serum.
AB  - In this work, the multi-walled carbon nanotubes were covalently functionalized
      with L-histidine (His-MWNTs) as online pseudospecific affinity adsorbent for
      immunoglobulin G (IgG) separation and purification with a simple surface
      modification method, using 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide
      hydrochloride (EDC) and N-hydroxysuccinimde (NHS). The affinity of the His-MWNTs
      toward IgG was investigated in a microcolumn incorporated into a sequential
      injection system, which also involves an UV spectrometer with a flow cell for
      online real-time detection. The incorporation of histidine as affinity groups
      noticeably increased the selectivity and binding capacity of MWNTs for IgG and
      the His-MWNTs exhibited high retention and recovery rate of nearly 100% under
      optimized conditions. This separation and enrichment process made it possible to
      determine a lower concentration range of IgG in serum from 1.0-33 MUg/mL with a
      detection limit of 0.3 MUg/mL with a sampling volume of 4.0 mL. The static and
      dynamic adsorption capacities obtained were 267 mg of IgG/g His-MWNTs and 35 mg/g
      in aqueous solution, respectively, which are among the highest reported results
      in literatures employing affinity separation methods. Desorption of IgG from His
      MWNTs could be accomplished by lowering the pH to 1.5 with glycine-HCl buffer.
      The practical application of His-MWNTs for separation of IgG in serum was
      evaluated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis which
      confirmed that the purity of recovered IgG from human serum was over 85% and
      better than a commercial product.

PMID- 22967520
TI  - A swelling-based chemiresistor for a biogenic odour.
AB  - Escherichia coli bacteria release 1-decanol as a byproduct of their metabolism.
      We demonstrate the detection of 1-decanol odour at a partial pressure in the
      order 100 ppb by the resistance change of a swelling-based sensor, consisting of
      Langmuir-Schafer deposited Au core/organic ligand shell nanoparticle films. This
      is an exceptionally low limit of detection for swelling-based sensors, and relies
      firstly, in the careful matching of the CSNPs ligands to the targeted odour, and
      secondly, in the very low volatility of this odour. Sensor response can be
      substantially increased further when films are cooled below the freezing point of
      1-decanol. We observe unexpected quantitative behaviour of our sensors: response
      is only weakly dependent on the odour's partial pressure, and scales differently
      with temperature than the response of other Au-CSNP odours to more volatile
      odours. This may be related to their unusually strong thermal resistance drift,
      the difficulties in delivering very low partial pressure odour atmospheres, and
      the proximity to the analyte's freezing point.

PMID- 22967521
TI  - Application of three phase hollow fiber based liquid phase microextraction (HF
      LPME) for the simultaneous HPLC determination of phenol substituting compounds
      (alkyl-, chloro- and nitrophenols).
AB  - This work proposes for the first time the use of a three phase hollow fiber
      liquid phase microextraction (HF-LPME) procedure for the simultaneous extraction,
      and the later HPLC determination, of some phenol substituting compounds (alkyl-,
      chloro- and nitrophenols) that are considered as highly toxic compounds and/or
      endocrine disrupting ones. The substances studied include four chlorophenols
      (CPs): 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,6
      dichlorophenol (2,6-DCP) and pentachlorophenol (PCP), three nitrophenols (NPs):
      2,4-dinitrophenol (2,4-DNP), 2,5-dinitrophenol (2,5-DNP) and 2,6-dinitriphenol
      (2,6-DNP) and two alkylphenols (APs): tert butylphenol (TBP) and sec butylphenol
      (SBP). The extraction was carried out through a dihexyl ether liquid membrane
      supported on an Accurel((r)) Q3/2 polypropylene hollow fiber. Optimum pH for
      donor and acceptor phases and extraction time were established. The enrichment
      (preconcentration) factors obtained were between 30 and 700 that allows detection
      limits between 140 and 290 pg mL(-1). The method was successfully applied to the
      determination of the compounds in environmental water samples, including urban
      wastewaters.

PMID- 22967522
TI  - Dispersive micro-solid phase extraction of ortho-phosphate ions onto magnetite
      nanoparticles and determination as its molybdenum blue complex.
AB  - A direct microextraction method, employing dispersive micro-solid phase
      extraction (MU-SPE) of ortho-phosphate (o-PO(4)(3-)) anions onto ferromagnetic
      nanoparticles (MNPs) is described in this work for the first time. The method
      exploits the complexation of phosphate ions on the surface of positively charged
      magnetite nanoparticles through the formation of an inner sphere complex, which
      are separated from the bulk aqueous phase with the application of an adscititious
      magnetic field. Phosphates are eluted with sodium bicarbonate and determined
      spectrophotometrically as their phosphomolybdenum blue complex. The method is
      generally free from common interferences, likely to affect the measurement of
      phosphate, since it alleviates their presence already from the extraction step,
      thus they are absent during detection. The detection limits are as low as 0.01
      MUM with very satisfactory precision ranging from 3.68% (intra-day) to 8.5%
      (inter-day) and accuracy between 91.5% and 104.8%.

PMID- 22967523
TI  - Highly sensitive synchronous fluorescence determination of mercury (II) based on
      the denatured ovalbumin coated CdTe QDs.
AB  - Chemically denatured ovalbumin (dOB) was used to modify the surface of 3
      mercaptopropionic acid (MPA) stabilized CdTe quantum dots (QDs), which resulted
      in a great enhancement of the synchronous fluorescence intensity. Moreover, dOB
      shell layer can effectively prevent the binding of other cations onto the QDs
      core and enhance the selective binding ability of Hg(2+) to dOB coated CdTe QDs
      (CdTe-dOB QDs). A simple method with high sensitivity and selectivity was
      developed for the determination of Hg(2+) with the CdTe-dOB QDs as fluorescence
      probe based on the merits of synchronous fluorescence spectroscopy (SFS). When
      scanning with excitation and emission wavelengths of 250 nm and 470 nm
      (Deltalambda=lambda(em)-lambda(ex)=220 nm), respectively, the maximum synchronous
      fluorescence peak of the CdTe-dOB QDs was located at 328 nm. Under optimal
      conditions, the change of the synchronous fluorescence intensity was in good
      linear relationship with the Hg(2+) concentration in the range of 0.08*10(-7) to
      30.0*10(-7) mol L(-1) and the detection limit was 4.2*10(-9) mol L(-1) (S/N=3).
      The relative standard deviation of seven replicate measurements for the
      concentration of 2.0*10(-7) mol L(-1) and 20.0*10(-7) mol L(-1) were 2.8% and
      2.3%, respectively. Compared with general fluorescence methods, the proposed
      method, which combined the advantages of high sensitivity of synchronous
      fluorescence and specific response of Hg(2+) to CdTe-dOB, had a wider linear
      range and higher sensitivity. Furthermore, the proposed method was applied to the
      determination of trace Hg(2+) in water samples with satisfactory results.

PMID- 22967524
TI  - Determination of 16 polycyclic aromatic hydrocarbons in seawater using
      molecularly imprinted solid-phase extraction coupled with gas chromatography-mass
      spectrometry.
AB  - A method of solid-phase extraction (SPE) using molecularly imprinted polymers
      (MIPs) as adsorbent coupled with gas chromatography-mass spectrometry (GC-MS) was
      developed for the determination of 16 types of polycyclic aromatic hydrocarbons
      (PAHs) in seawater samples. The MIPs were prepared through non-covalent
      polymerization by using the 16 PAHs mixture as a template based on sol-gel
      surface imprinting. Compared with the non-imprinted polymers (NIPs), the MIPs
      exhibited excellent affinity towards 16 PAHs with binding capacity of 111.0-195.0
      MUg g(-1), and imprinting factor of 1.50-3.12. The significant binding
      specificity towards PAHs even in the presence of environmental parameters such as
      dissolved organic matter and various metal ions, suggested that this new
      imprinting material was capable of removing 93.2% PAHs in natural seawater. High
      sensitivity was attained, with the low limits of detection for 16 PAHs in natural
      seawater ranging from 5.2-12.6 ng L(-1). The application of MIPs with high
      affinity and excellent stereo-selectivity toward PAHs in SPE might offer a more
      attractive alternative to conventional sorbents for extraction and abatement of
      PAH-contaminated seawater.

PMID- 22967525
TI  - Preparation of Cr(VI) and Cr(III) isotopic spike solutions from 50Cr and 53Cr
      enriched oxides without the use of oxidizing and/or reducing agents.
AB  - The use of enriched stable isotopes as tracers in speciation procedures by ion
      exchange chromatography coupled to ICP-MS enables to follow the oxidation
      reduction processes of Cr. The most commonly available Cr stable isotopes are
      (50)Cr and (53)Cr enriched oxides or metallic Cr. For application of Cr enriched
      stable isotopes, adequate preparation of isotopic spike solutions is necessary.
      To ensure that Cr species present in the sample investigated are not compromised,
      no excess of the reducing neither oxidizing agents should remain in the isotopic
      spike solutions. Cr(VI) isotopic solutions are mostly prepared by dissolving of
      Cr oxide in HClO(4), followed by the addition of ammonia and H(2)O(2) to
      quantitatively oxidize Cr, while the excess of H(2)O(2) is removed by boiling or
      UV irradiation. If traces of H(2)O(2) still remains, such isotopic spike solution
      may cause artefacts in Cr speciation in the sample investigated. In the present
      work, new procedure based on alkaline melting of (50)Cr enriched oxide for
      preparation of pure (50)Cr(VI) spike solution was developed. Cr(III) was
      quantitatively oxidized to Cr(VI) with air oxygen without use of other oxidizing
      agents. Moreover, the microwave assisted digestion procedure of (53)Cr enriched
      oxide was applied for preparation of (53)Cr(III) spike solution without use of
      reducing agents. The purity of (50)Cr(VI) and (53)Cr(III) isotopic spike
      solutions was verified by the speciation analysis applying hyphenation of anion
      exchange FPLC to ICP-MS. Speciation analysis demonstrated suitability of the
      proposed procedures for preparation of Cr isotopic spike solutions. In addition,
      the artefacts in Cr speciation, which may be initiated by traces of oxidizing
      and/or reducing agents present in Cr spike solutions, were demonstrated. The
      outcomes of our investigation highlighted the importance of the adequate
      preparation of spike solutions of Cr isotopes that may be used as reliable
      tracers in the investigations of the oxidation-reduction processes of Cr in wide
      range of environmentally relevant pH values.

PMID- 22967526
TI  - Preparation and characterization of neutral poly(ethylene glycol) methacrylate
      based monolith for normal phase liquid chromatography.
AB  - A novel porous poly(ethylene glycol) methacrylate-based monolithic column for
      normal phase liquid chromatography was prepared by thermally initiated
      polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and
      ethylene dimethacrylate (EDMA) in the presence of selected porogens. The monolith
      was macroscopically homogeneous, had low flow resistance, and did not swell or
      shrink significantly in solvents of different polarities. Inverse size-exclusion
      data indicate that the monolith had a total porosity of 79.2%, including an
      external porosity of 69.3% and an internal porosity of 9.9%. Due to its mild
      polarity (hydrophilicity), the PEG-functionalized monolith could perform
      traditional normal phase chromatography using non-polar solvents The van Deemter
      plot demonstrated that the column efficiency of 33,600-34,320 theoretical
      plates/m could be achieved at a linear flow velocity of 0.9-1.5mm/s. The dual
      retention capability (both weak hydrophilic and hydrophobic interactions)
      investigated in this paper explains well why the PEG-functionalized monolith
      could operate in various chromatographic modes.

PMID- 22967527
TI  - Certified reference material of bioethanol for metrological traceability in
      electrochemical parameters analyses.
AB  - Bioethanol has become an important biofuel because it is a source of renewable
      energy and can help to decrease global warming. However, the quality of
      bioethanol needs to be guaranteed so that it can be trusted and accepted in
      international trade. The Brazilian Metrology Institute (Inmetro) has been
      developing a certified reference material (CRM) for bioethanol to ensure quality
      control for measurement in the bioethanol matrix. Inmetro has certified 11
      quality parameters. Using these, the CRM of bioethanol will contribute to
      guaranteeing metrological traceability and reliable measurement results. These
      factors can be used to compare different bioethanols produced to comply with
      legislation in different countries in order to avoid technical barriers and thus
      increase the international trade in Brazilian bioethanol. The aim of this paper
      is to present the results of certification studies using three important
      electrochemical quality parameters in the CRM of bioethanol-total acid number,
      pHe and electrolytic conductivity-which are crucial in protecting the metallic
      parts of a vehicle from corrosion. The certified results obtained for total acid
      number, pHe and electrolytic conductivity parameters were (16.2+/-1.7)mg L(-1),
      6.07+/-0.30, and (1.03+/-0.11)MUS cm(-1), respectively. The uncertainties for all
      parameters were the expanded uncertainty obtained by multiplying the combined
      standard uncertainty by a coverage factor of k=2, which represents an
      approximately 95% confidence level.

PMID- 22967528
TI  - Application of the extraction induced by emulsion breaking for the determination
      of chromium and manganese in edible oils by electrothermal atomic absorption
      spectrometry.
AB  - This work reports the optimization of a method, based on the extraction induced
      by emulsion breaking, for the determination of trace concentrations of Cr and Mn
      in edible oils by electrothermal atomic absorption spectrometry (ETAAS). In the
      method, a water-in-oil emulsion was prepared by mixing the oil sample with an
      acid solution (HNO(3)) of Triton X-114 to allow the intense contact between the
      sample and the extractant acid solution. Afterwards, the emulsion was broken by
      heating and the acid aqueous phase deposited in the bottom of the flask was
      collected for the determination of the metals of interest. The method was
      optimized by studying the influence of several parameters such as the
      concentration of HNO(3) and the emulsifier agent (Triton X-100 and Triton X-114)
      in the extractant solution. The best results were verified when the procedure was
      performed with 5 mL of the sample and 1 mL of the extractant solution containing
      15%m/v of Triton X-114 and 2.8 mol L(-1) of HNO(3). Also, the fastest emulsion
      breaking was verified when the emulsions were heated at 90 degrees C. In these
      conditions, the emulsions were broken in approximately 10 min. The quantification
      of Cr and Mn in the extracts was carried out by external calibration with aqueous
      standard solutions, which simplified the procedure. The limits of detection for
      the determination of Cr and Mn in the oil samples were 66 and 36 ng L(-1),
      respectively, and the limits of quantification were 219 and 120 ng L(-1),
      respectively. The developed method was applied in the determination of Cr and Mn
      in twelve samples of edible oils produced with different oleaginous. Recovery
      tests were performed to attest the accuracy of the method, being observed
      recovery percentages in the range of 86-115%.

PMID- 22967529
TI  - Novel surface plasmon resonance sensor for the detection of heme at biological
      levels via highly selective recognition by apo-hemoglobin.
AB  - We have developed a novel surface plasmon resonance (SPR) biosensor for heme
      detection that utilizes the reconstitution of the heme cofactor with
      apohemoglobin (apoHb), hemoglobin from which the heme has been removed, as the
      sensing mechanism. The binding is highly specific, efficient and generated very
      strong SPR signals. This is the first report that uses immobilization of the
      apoprotein in a hydrophilic polymer matrix and senses the corresponding cofactor
      by SPR. This is also the first report of high sensitivity heme detection in real
      time by SPR and the sensing surface is re-generated many times without loss of
      sensitivity or selectivity. The sensing surface was fabricated by covalent
      immobilization of hemoglobin in a polyacrylic acid matrix in situ, which allowed
      for a high concentration of protein to be located in the plasmon detection range
      on the Au chip. Removal of the heme from the hemoglobin-polymer conjugate (Hb
      PAA) resulted in a surface anchored apoHb-polymer conjugate. The limit of
      detection was approximately 2 MUM or 1.30 MUg/mL, which is relevant for
      biological heme levels (1-50 MUM for hemolytic pathological conditions). This
      apoHb-polyacrylic acid system demonstrates a new concept in SPR detection with
      the use of protein cofactor binding pockets for analyte detection. The
      methodology that we developed here may be extended for the detection of a number
      of other cofactor molecules with high sensitivity, selectivity and low detection
      limits. In future, such sensors could be useful for the development of point-of
      care devices to detect biologically important small molecules.

PMID- 22967530
TI  - Nafion-mercury coated film electrode for the adsorptive stripping voltammetric
      determination of lead and cadmium in the presence of pyrogallol red.
AB  - An adsorptive stripping voltammetric (AdSV) method is presented for the
      simultaneous determination of Pb(II) and Cd(II) at trace levels in natural
      waters, based on metal complexation with pyrogallol red (PR) and subsequent
      adsorptive deposition on a Nafion-mercury coated glassy carbon electrode (NHgFE).
      Pyrogallol red forms complexes with a metal:ligand stoichiometry of 1:1 with
      Pb(II) and of 1:2 with Cd(II). Optimal analytical conditions were pH 4.0 (acetate
      buffer); C(PR)=2.8 MUmol L(-1); E(ads)=-0.40 V vs. Ag/AgCl; t(ads)=100 s. The
      linear calibration curves ranged from 1.0 MUg L(-1) to 16.0 MUg L(-1) for Pb(II)
      and from 1.0 MUg L(-1) to 13.0 MUg L(-1) for Cd(II). The detection limits (S/N=3)
      were 0.05 MUg L(-1) for Pb(II) and 0.01 MUg L(-1) for Cd(II). The relative
      standard deviation was 1.0% and 2.0% (n=7), respectively, for a solution
      containing 5.0 MUg L(-1) Pb(II) and Cd(II). The method was validated by
      determining Pb(II) and Cd(II) in certified reference waste water (SPS-WW1).
      Finally, the method was applied to the determination of Pb(II) and Cd(II) in
      commercial mineral water samples after UV digestion.

PMID- 22967531
TI  - Development of a polyclonal antibody-based enzyme-linked immunosorbent assay
      (ELISA) for detection of Sunset Yellow FCF in food samples.
AB  - Sunset Yellow FCF is widely used as food additives to make foods more attractive.
      Due to its abuse and potential risk to human health, Sunset Yellow FCF is
      precisely limited to use in food. To monitor the illegal use of Sunset Yellow
      FCF, a polyclonal antibody-based indirect competitive enzyme-linked immunosorbent
      assay (ic-ELISA) with satisfactory sensitivity and specificity was developed. A
      carboxyl group was introduced to Sunset Yellow FCF, then the modified hapten was
      coupled with carrier proteins to synthesize the immunogen and coating antigen.
      The IC(50) value of 0.52 ng mL(-1) and detection limit of 25 pg mL(-1) (in
      buffer) were achieved by this method. The cross-reactivity values of the
      antibodies with six structurally related colorants were less than 1.5%,
      indicating the high selectivity. Three kinds of food samples (beverage, dried
      beancurd, braised pork) and serum were chosen to evaluate the application of the
      immunoassay in real systems. The limits of detection (LOD) in the above three
      food samples were 0.12, 0.04 and 1.11, respectively (mean+3SD). The recovery (94%
      106%), intra-assay (<5%) and inter-assay (<12%) coefficients of variation in
      foods and serum samples were also acceptable. The results suggest that this ELISA
      method is a specific, sensitive and simple method for the determination of Sunset
      Yellow FCF additives.

PMID- 22967532
TI  - Synthesis and characterization of magnetic metal-organic framework (MOF) as a
      novel sorbent, and its optimization by experimental design methodology for
      determination of palladium in environmental samples.
AB  - This paper describes the synthesis and application of novel magnetic metal
      organic framework (MOF) [(Fe(3)O(4)-Pyridine)/Cu(3)(BTC)(2)] for preconcentration
      of Pd(II) and its determination by flame atomic absorption spectrometry (FAAS). A
      Box-Behnken design was used to find the optimum conditions for the
      preconcentration procedure through response surface methodology. Three variables
      including amount of magnetic MOF, extraction time, and pH of extraction were
      selected as factors for adsorption step, and in desorption step, four parameters
      including type, volume, and concentration of eluent, and desorption time were
      selected in the optimization study. These values were 30 mg, 6 min, 6.9,
      K(2)SO(4)+NaOH, 6 mL, 9.5 (w/v %)+0.01 mol L(-1), 15.5 min, for amount of MOF,
      extraction time, pH of extraction, type, volume, and concentration of the eluent,
      and desorption time, respectively. The preconcentration factor (PF), relative
      standard deviation (RSD), limit of detection (LOD), and adsorption capacity of
      the method were found to be 208, 2.1%, 0.37 ng mL(-1), and 105.1 mg g(-1),
      respectively. It was found that the magnetic MOF has more capacity compared to
      Fe(3)O(4)-Py. Finally, the magnetic MOF was successfully applied for rapid
      extraction of trace amounts of Pd (II) ions in fish, sediment, soil, and water
      samples.

PMID- 22967534
TI  - Analysis of N-nitrosamines in water by isotope dilution gas chromatography
      electron ionisation tandem mass spectrometry.
AB  - A method has been developed for the determination of eight N-nitrosamines in
      drinking water and treated municipal effluent. The method uses solid phase
      extraction (SPE), gas chromatography (GC) and analysis by tandem mass
      spectrometry (MS-MS) with electron ionization (EI). The target compounds are N
      nitrosodimethylamine (NDMA), N-nitrosomethyethylamine (NMEA), N
      nitrosodiethylamine NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodi-n
      butylamine (NDBuA), N-nitrosodiphenylamine (NDPhA), N-nitrosopyrrolidine (NPyr),
      N-nitrosopiperidine (NPip), N-nitrosomorpholine (NMorph). The use of direct
      isotope analogues for isotope dilution analysis of all analytes ensures accurate
      quantification, accounting for analytical variabilities that may occur during
      sample processing, extraction and instrumental analysis. Method detection levels
      (MDLs) were determined to describe analyte concentrations sufficient to provide a
      signal with 99% certainty of detection. The established MDLs for all analytes
      were 0.4-4 ng L(-1) in a variety of aqueous matrices. Sample matrices were
      observed to have only a minor impact on MDLs and the method validation confirmed
      satisfactory method stability over intra-day and inter-day analyses of tap water
      and tertiary treated effluent samples.

PMID- 22967533
TI  - Laser spectrochemical characterization of semen.
AB  - The overall objective of this paper is to use a fast, more sensitive and less
      costly spectrochemical analysis laser techniques for estimation of seasonal
      variation of elements present in seminal plasma as well as for semen sperm count.
      For these two tasks we used Laser Induced-Breakdown Spectroscopy (LIBS) as an
      elemental analysis technique and Laser Induced Fluorescence (LIF) as a molecular
      analysis technique for sperm count estimation. The samples investigated via both
      techniques were buffalo semen from the artificial insemination center at the
      faculty of agriculture. The obtained LIBS data helped to assess indirectly the
      semen quality, sperm motility and spermatozoa count, relevant to the studied
      elements in different seasons. In addition it has been demonstrated that LIF can
      be adopted directly in centers of artificial insemination as a simple and fast
      method for the essential step of semen counting instead of the lengthy and
      inaccurate conventional techniques.

PMID- 22967536
TI  - Multiple testing of food contact materials: a predictive algorithm for assessing
      the global migration from silicone moulds.
AB  - For reasons of food safety, packaging and food contact materials must be
      submitted to migration tests. Testing of silicone moulds is often very laborious,
      since three replicate tests are required to decide about their compliancy. This
      paper presents a general modelling framework to predict the sample's compliance
      or non-compliance using results of the first two migration tests. It compares the
      outcomes of models with multiple continuous predictors with a class of models
      involving latent and dummy variables. The model's prediction ability was tested
      using cross and external validations, i.e. model revalidation each time a new
      measurement set became available. At the overall migration limit of 10 mg dm(-2),
      the relative uncertainty on a prediction was estimated to be ~10%. Taking the
      default values for alpha and beta equal to 0.05, the maximum value that can be
      predicted for sample compliance was therefore 7 mg dm(-2). Beyond this limit the
      risk for false compliant results increases significantly, and a third migration
      test should be performed. The result of this latter test defines the sample's
      compliance or non-compliance. Propositions for compliancy control inspired by the
      current dioxin control strategy are discussed.

PMID- 22967535
TI  - Greatly extended storage stability of electrochemical DNA biosensors using
      ternary thiolated self-assembled monolayers.
AB  - While high storage stability of sequence-selective DNA biosensors is crucial
      towards their routine applications, commonly used electrochemical hybridization
      biosensors are characterized with limited storage stability. In this article we
      demonstrate that recently developed ternary thiolated monolayers impart dramatic
      improvement in the storage stability of DNA electrochemical biosensors. In
      particular, highly stable multicomponent interfaces are prepared by co
      immobilizing the thiolated capture probe (SHCP) with 1,6-hexanedithiol (HDT) on
      gold substrates, followed by the incorporation of 6-mercapto-1-hexanol (MCH)
      diluent. The resulting (SHCP/HDT+MCH) DNA hybridization recognition platform
      offers substantially higher storage stability compared to conventional binary
      (SHCP+MCH) monolayers. The (SHCP/HDT+MCH) ternary monolayers maintain their
      initial signal (S)-to-noise (N) ratio (S/N) over a prolonged 3 months period upon
      storage at 4  degrees C, compared to the rapid sensitivity loss observed using
      the common binary interfaces. This attractive stability performance promises the
      convenient usage of pre-prepared electrodes after prolonged time storage without
      any treatment. Such dramatic improvements in the storage stability have been
      achieved through a rational optimization of the concentration ratio of the SHCP
      and the other components of the ternary SAM. The improved storage stability of
      SHCP/HDT+MCH interfaces observed at higher concentrations of SHCP is attributed
      to a hindered displacement of SHCP by MCH in the resulting compact layers. The
      ability to design highly stable nucleic acid interfaces using common chemicals
      obviates the need of using specialized expensive reagents.

PMID- 22967537
TI  - Determination of bisphenol-type endocrine disrupting compounds in food-contact
      recycled-paper materials by focused ultrasonic solid-liquid extraction and ultra
      performance liquid chromatography-high resolution mass spectrometry.
AB  - Focused ultrasonic solid-liquid extraction (FUSLE) and reverse-phase ultra
      performance liquid chromatography (UPLC) coupled to a quadrupole-time of flight
      mass spectrometer (Q-TOF-MS) was applied to the determination of bisphenol-type
      endocrine disrupting compounds (EDCs) in food-contact recycled-paper materials.
      Recycled paper is a potential source of EDCs. Bisphenol A (BPA), bisphenol F
      (BPF) and their derivatives bisphenol A diglycidyl ether (BADGE) and bisphenol F
      diglycidyl ether (BFDGE) are used for the production of epoxy resins employed in
      the formulation of printing inks. The FUSLE of bisphenol-type EDCs from packaging
      is reported for the first time. First, different extraction solvents were studied
      and methanol was selected. Then, the main FUSLE factors affecting the extraction
      efficiency (solvent volume, extraction time and ultrasonic irradiation power)
      were studied by means of a central composite design. The FUSLE conditions
      selected for further experiments were 20 ml of methanol at ultrasonic amplitude
      of 100% for 5s. Finally, the number of extraction cycles necessary for complete
      extraction was established in two. The analysis of the FUSLE extracts was carried
      out by UPLC-Q-TOF-MS with electrospray ionization and the determination of the
      four analytes took place in only 4 min. The FUSLE and UPLC-ESI-QTOF-MS method was
      validated and applied to the analysis of different food-contact recycled-paper
      based materials and packaging. The proposed method provided recoveries from 72%
      to 97%, repeatability and intermediate precision under 9% and 14%, respectively,
      and detection limits of 0.33, 0.16, 0.65 and 0.40 MUg/g for BPA, BPF, BADGE and
      BFDGE, respectively. The analysis of paper and cardboard samples confirmed the
      presence of EDCs in these packaging.

PMID- 22967539
TI  - Portable mercury sensor for tap water using surface plasmon resonance of
      immobilized gold nanorods.
AB  - The surface plasmon resonance of surface immobilized gold nanorods (Au NRs) was
      used to quantify mercury in tap water. Glass substrates were chemically
      functionalized with (3-mercaptopropyl)trimethoxysilane, which chemically bound
      the nanorods to produce a portable and sensitive mercury sensor. The analytical
      capabilities of the sensor were measured using micromolar mercury concentrations.
      Since the analytical response was dependent upon number of nanorods present, the
      limit of detection was 2.28*10(-19) M mercury per nanorod. The possibility to
      using glass substrates with immobilized Au NRs is a significant step towards the
      analysis of mercury in tap water flows at this low concentration level.

PMID- 22967538
TI  - Detection of addition of barley to coffee using near infrared spectroscopy and
      chemometric techniques.
AB  - The current study presents an application of near infrared spectroscopy for
      identification and quantification of the fraudulent addition of barley in roasted
      and ground coffee samples. Nine different types of coffee including pure Arabica,
      Robusta and mixtures of them at different roasting degrees were blended with four
      types of barley. The blending degrees were between 2 and 20 wt% of barley. D
      optimal design was applied to select 100 and 30 experiments to be used as
      calibration and test set, respectively. Partial least squares regression (PLS)
      was employed to build the models aimed at predicting the amounts of barley in
      coffee samples. In order to obtain simplified models, taking into account only
      informative regions of the spectral profiles, a genetic algorithm (GA) was
      applied. A completely independent external set was also used to test the model
      performances. The models showed excellent predictive ability with root mean
      square errors (RMSE) for the test and external set equal to 1.4% w/w and 0.8%
      w/w, respectively.

PMID- 22967540
TI  - Synthesis and application of a Sec2-containing oligopeptide for method evaluation
      purposes in selenium speciation.
AB  - Sec(2)-containing oligopeptide was synthesized directly from Sec(2) with the
      traditional liquid phase peptide synthesis without addressing the usually applied
      and complex solid phase (SPPS) protocol driving through a protected Sec residue
      and site-oriented oxidation into a diselenide bridge. Effective solubilization of
      Sec(2) in dimethylformamide and its pH-controlled access to pentachlorophenol
      activated peptides to couple with were of crucial importance to achieve good
      yield (>50%) of synthesis, monitored by HPLC-UV, SEC-ICP-MS and HPLC-ESI-MS
      techniques. To demonstrate the possible application of the new compound, (Boc
      GGFG)-Sec(2)-(Boc-GGFG) (m/z 1173.3, [M+H](+)), it was utilized to compare the
      effect of the two most addressed sample preparation techniques, i.e.,
      methanesulphonic acid (MSA) based digestion and proteolytic digestion with
      protease XIV, on the Sec residue. The study revealed that the use of MSA resulted
      in the decomposition of Sec even after derivatization with iodoacetamide.

PMID- 22967541
TI  - New fluorescent pH sensors based on covalently linkable PET rhodamines.
AB  - A new class of rhodamines for the application as indicator dyes in fluorescent pH
      sensors is presented. Their pH-sensitivity derives from photoinduced electron
      transfer between non-protonated amino groups and the excited chromophore which
      results in effective fluorescence quenching at increasing pH. The new indicator
      class carries a pentafluorophenyl group at the 9-position of the xanthene core
      where other rhodamines bear 2-carboxyphenyl substituents instead. The
      pentafluorophenyl group is used for covalent coupling to sensor matrices by
      "click" reaction with mercapto groups. Photophysical properties are similar to
      "classical" rhodamines carrying 2'-carboxy groups. pH sensors have been prepared
      with two different matrix materials, silica gel and poly(2
      hydroxyethylmethacrylate). Both sensors show high luminescence brightness
      (absolute fluorescence quantum yield Phi(F)~0.6) and high pH-sensitivity at pH 5
      7 which makes them suitable for monitoring biotechnological samples. To underline
      practical applicability, a dually lifetime referenced sensor containing Cr(III)
      doped Al(2)O(3) as reference material is presented.

PMID- 22967542
TI  - Application of a new capillary electrophoretic method for the determination of
      carbohydrates in forensic, pharmaceutical, and beverage samples.
AB  - A new capillary electrophoresis method dedicated to the analysis of neutral
      underivatized carbohydrates was recently developed by our group. It involved a
      background electrolyte composed of 98 mM NaOH and 120 mM NaCl, and direct UV
      detection via the formation of an absorbing intermediate in the detection window
      by photooxidation. This article focuses on the validation of this method for the
      determination of fructose, glucose, lactose, and sucrose in forensic,
      pharmaceutical, and beverage samples. Intermediate precisions were about 2.3% for
      normalized corrected peak areas and 1.8% for normalized migration times using
      naphthalenesulfonate as internal standard. Limits of detection varying from 5 MUM
      for sucrose and lactose to 7 MUM for glucose and 10 MUM for fructose were
      obtained. Potential matrix effects were statistically studied for soil, cloth,
      plastic, cotton, red wine, and with simulated iron, calcium, and sucrose-based
      matrices, containing various inorganic anions and cations, sometimes at high
      levels. No significant matrix effect was observed. Finally, analyses of real post
      explosion residues, smoke device, cough syrup, red wine, and apple juice were
      successfully performed.

PMID- 22967543
TI  - Analysis of twenty five impurities in uranium matrix by ICP-MS with iron
      measurement optimized by using reaction collision cell, cold plasma or medium
      resolution.
AB  - An analytical procedure was developed to determine the concentration of 25
      impurities (Li, Be, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Zr, Mo, Ag, Cd, In, Sm,
      Eu, Gd, Dy, W, Pb, Bi and Th) in a uranium matrix using the quadrupole
      inductively coupled plasma mass spectrometry (Q-ICP-MS). The dissolution of
      U(3)O(8) powder was made with a mixture of hydrochloric acid and nitric acid.
      Then, a selective separation of uranium using the UTEVA column was used before
      measurement by Q-ICP-MS. The procedure developed was verified using the Certified
      Reference Material "Morille". The analytical results agree well except for 5
      elements where values are underestimated (Li, Be, In, Pb and Bi). Among the list
      of impurities, iron was particularly investigated because it is well known that
      this element possesses a polyatomic interference that increases the detection
      limit. A comparison between iron detection limits obtained with different methods
      was performed. Iron polyatomic interference was at least reduced, or at best
      entirely resolved in some cases, by using the cold plasma or the
      collision/reaction cell with several gases (He, NH(3) and CH(4)). High-resolution
      ICP-MS was used to compare the results obtained. A detection limit as low as 8 ng
      L(-1) was achieved.

PMID- 22967544
TI  - On line characterization of 58 phenolic compounds in Citrus fruit juices from
      Spanish cultivars by high-performance liquid chromatography with photodiode-array
      detection coupled to electrospray ionization triple quadrupole mass spectrometry.
AB  - Polyphenol profile of Citrus juices of sweet orange, tangerine, lemon and
      grapefruit from Spanish cultivars was obtained by High-Performance Liquid
      Chromatography with Diode Array Detection coupled to Electrospray ionization and
      Triple Quadrupole Mass Spectrometry. Fifty eight phenolic compounds of five
      different classes were identified in these Citrus juices. Flavanone: O-dihexoside
      of naringenin; flavones: apigenin-7-O-rutinoside-4'-O-glucoside, luteolin-7-O
      neohesperidoside-4'-O-glucoside, luteolin-6-C-glucoside, 6,8-di-C-acylhexosides
      of chrysoeriol and diosmetin, 6C- and 8C-glucoside-O-pentoside of apigenin,
      apigenin-6-C-hexoside-O-hexoside and apigenin-8-C-hexoside-O-acylrhamnoside;
      flavonols: 7-O-rutinosides of quercetin, kaempferol, isorhamnetin and
      tamarixetin, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside-7-O
      glucoside, tamarixetin-3-O-rutinoside-7-O-glucoside, isorhamnetin-3-O-hexoside-7
      O-rhamnosylhexoside, 3-O-rhamnoside-7-O-rhamnosylhexoside of quercetin and
      isorhamnetin and kaempferol-3-O-rhamnosylhexoside-7-O-rhamnoside; hydroxycinnamic
      acids: O-hexoside of ferulic and sinapic acid; and, coumarins: O-hexoside and O
      rhamnosylhexoside of scopoletin, had not previously been reported in Citrus
      juices to our knowledge. Structures have been assigned on the basis of the
      complementary information obtained from retention time, UV-visible spectra, scan
      mode MS spectra, and fragmentation patterns in MS(2) spectra obtained using
      different collision energies. A structure diagnosis scheme is provided for the
      identification of different phenolic compounds.

PMID- 22967545
TI  - 3-Methyl-2-butene-1-thiol: identification, analysis, occurrence and sensory role
      of an uncommon thiol in wine.
AB  - A highly uncommon odorant, 3-methyl-2-butene-1-thiol was detected by using Gas
      Chromatography-Olfactometry (GC-O) and unequivocally identified for the first
      time in wine. A purge and trap sampling technique which provides highly
      representative extracts for olfactometric analysis was used for the extraction of
      the volatile fraction of a Spanish red wine made from Prieto Picudo grapes. The
      identification of the odorant was achieved by multidimensional gas chromatography
      analysis of the same purge and trap extract. Mass spectrum and retention indices
      in both polar and non-polar columns allowed knowing unequivocally the identity.
      To obtain quantitative data a method was validated for the analysis of the
      compound at ng L(-1) level with acceptable precision. This powerful odorant
      presented an odor threshold in wine of 0.5-1 ng L(-1) and it has been detected in
      several Prieto Picudo wines at concentrations slightly above the odor threshold.

PMID- 22967546
TI  - Automated flow-through amperometric immunosensor for highly sensitive and on-line
      detection of okadaic acid in mussel sample.
AB  - An electrochemical immunosensor for okadaic acid (OA) detection has been
      developed, and used in an indirect competitive immunoassay format under automated
      flow conditions. The biosensor was fabricated by injecting OA modified magnetic
      beads onto screen printed carbon electrode (SPCE) in the flow system. The OA
      present in the sample competed with the immobilized OA to bind with anti-okadaic
      acid monoclonal antibody (anti-OA-MAb). The secondary alkaline phosphatase
      labeled antibody was used to perform electrochemical detection. The current
      response obtained from the labeled alkaline phosphatase to 1-naphthyl phosphate
      decreased proportionally to the concentration of free OA in the sample. The
      calculated limit of detection (LOD) was 0.15 MUg/L with a linear range of 0.19-25
      MUg/L. The good recoveries percentages validated the immunosensor application for
      real mussel samples. The developed system automatically controlled the
      incubation, washing and current measurement steps, showing its potential use for
      OA determination in field analysis.

PMID- 22967547
TI  - Analysis of trenbolone acetate metabolites and melengestrol in environmental
      matrices using gas chromatography-tandem mass spectrometry.
AB  - Studies demonstrate that exposure to steroid hormones in receiving waters can
      adversely impact reproduction of aquatic organisms. In particular, exogenous
      steroid hormones widely used as growth promoters in animal agriculture are of
      high concern, yet no gas chromatography-tandem mass spectrometry (GC/MS/MS)
      analytical methods for the detection of these compounds in complex environmental
      matrices is described in the literature. This study utilizes analytical methods
      based upon N-methyl-N-(trimethylsilyl)trifluoro-acetamide-iodine (MSTFA-I(2))
      derivatization for the analysis of metabolites of trenbolone acetate (TBA),
      including 17alpha-trenbolone, 17beta-trenbolone, and trendione, and melengestrol
      acetate in receiving waters and surface soils associated with animal agriculture.
      Results suggest method detection levels of 0.5-1 ng/L for the trenbolone
      metabolites, while detection of melengestrol is qualitative only. Isotope
      dilution methods employing d3-17beta-trenbolone were used to improve steroid
      quantification. Method recoveries in spiked samples collected from a variety of
      representative receiving waters generally ranged from 80-120% with consistent and
      low standard deviation (generally<10%) for replicate analysis. Analysis of a
      storm water runoff sample from a commercial confined animal feeding operation
      (CAFO) that used TBA implants detected 17beta-trenbolone and trendione at
      concentrations of 31 and 52 ng/L, respectively. Analysis of surface soils at a
      commercial CAFO using TBA implants detected 17alpha-trenbolone at concentrations
      between 4-6 ng/g dry weight. Method development efforts suggested that the
      concentration of I(2) in MSTFA, the removal of I(2) from sample extracts after
      derivatization, and the use of Florisil clean-up to reduce organic matter matrix
      were vital aspects of steroid hormone quantification at low (<30ng/L)
      concentrations in complex environmental matrices.

PMID- 22967548
TI  - Carbamazepine in municipal wastewater and wastewater sludge: ultrafast
      quantification by laser diode thermal desorption-atmospheric pressure chemical
      ionization coupled with tandem mass spectrometry.
AB  - In this study, the distribution of the anti-epileptic drug carbamazepine (CBZ) in
      wastewater (WW) and aqueous and solid phases of wastewater sludge (WWS) was
      carried out. A rapid and reliable method enabling high-throughput sample analysis
      for quicker data generation, detection, and monitoring of CBZ in WW and WWS was
      developed and validated. The ultrafast method (15s per sample) is based on the
      laser diode thermal desorption-atmospheric pressure chemical ionization (LDTD
      APCI) coupled to tandem mass spectrometry (MS/MS). The optimization of
      instrumental parameters and method application for environmental analysis are
      presented. The performance of the novel method was evaluated by estimation of
      extraction recovery, linearity, precision and detection limit. The method
      detection limits was 12 ng L(-1) in WW and 3.4 ng g(-1) in WWS. The intra- and
      inter-day precisions were 8% and 11% in WW and 6% and 9% in WWS, respectively.
      Furthermore, three extraction methods, ultrasonic extraction (USE), microwave
      assisted extraction (MAE) and accelerated solvent extraction (ASE) with three
      different solvent condition such as methanol, acetone and acetonitrile:ethyle
      acetate (5:1, v/v) were compared on the basis of procedural blank and method
      recovery. Overall, ASE showed the best extraction efficiency with methanol as
      compared to USE and MAE. Furthermore, the quantification of CBZ in WW and WWS
      samples showed the presence of contaminant in all stages of the treatment plant.

PMID- 22967549
TI  - Nanocomposites of palladium nanoparticle-loaded mesoporous carbon nanospheres for
      the electrochemical determination of hydrogen peroxide.
AB  - Palladium nanoparticles (Pd NPs) were loaded in situ on novel mesoporous carbon
      nanospheres (MCNs), which possess high specific surface area and large pore
      volume. The resulting Pd/MCNs hybrid nanocomposites were characterized by X-ray
      diffraction (XRD) and transmission electron microscopy (TEM). By using Pd/MCNs as
      the catalyst matrices to modify the surface of glassy carbon electrode, a
      nonenzymatic sensor was developed for the determination of hydrogen peroxide
      (H(2)O(2)). Cyclic voltammetry (CV) and amperometry (at an applied potential of 
      0.30 V versus SCE) were used to study and optimize the performance of the
      electrochemical sensor. It was demonstrated that the sensor not only exhibits
      good electrocatalytic activity toward the reduction of H(2)O(2) but also has high
      sensitivity (307.5 MUA mM(-1) cm(-2)), low detection limit of 1.0 MUM, and wide
      linear response range from 7.5 MUM to 10 mM. Moreover, the sensor shows excellent
      stability and anti-interference capability for the detection of H(2)O(2).

PMID- 22967550
TI  - Characterization of diesel fuel by chemical separation combined with capillary
      gas chromatography (GC) isotope ratio mass spectrometry (IRMS).
AB  - The purpose of this study was to perform a preliminary investigation of compound
      specific isotope analysis (CSIA) of diesel fuels to evaluate whether the
      technique could distinguish diesel samples from different sources/locations. The
      ability to differentiate or correlate diesel samples could be valuable for
      discovering fuel tax evasion schemes or for environmental forensic studies. Two
      urea adduction-based techniques were used to isolate the n-alkanes from the fuel.
      Both carbon isotope ratio (delta(13)C) and hydrogen isotope ratio (deltaD) values
      for the n-alkanes were then determined by CSIA in each sample. The samples
      investigated had delta(13)C values that ranged from -30.10/00 to -26.80/00,
      whereas deltaD values ranged from -830/00 to -1560/00. Plots of deltaD versus
      delta(13)C with sample n-alkane points connected in order of increasing carbon
      number gave well-separated clusters with characteristic shapes for each sample.
      Principal components analysis (PCA) with delta(13)C, deltaD, or combined
      delta(13)C and deltaD data was applied to extract the maximum information
      content. PCA scores plots could clearly differentiate the samples, thereby
      demonstrating the potential of this approach for distinguishing (e.g.,
      fingerprinting) fuel samples using delta(13)C and deltaD values.

PMID- 22967551
TI  - Molecularly imprinted solid phase microextraction fiber for trace analysis of
      catecholamines in urine and serum samples by capillary electrophoresis.
AB  - A selective and flexible monolithic moleculary imprinted polymer (MIP) fiber was
      developed in batch for solid phase microextraction (SPME) of catecholamines
      (CAs), i.e., dopamine (DA), epinephrine (E) and norepinephrine (NE), and coupled
      with capillary electrophoresis (CE) for trace analysis of urine and serum
      samples. The polymer fiber was synthesized in-situ simply using a flexible
      capillary as a mold and the polymerization protocols and SPME experimental
      conditions were examined in detail. The reproducibility of fiber to fiber
      fabrication (n=5) was in range of 5.9-9.8% for three CAs. The fiber also shows
      high stability without any deterioration of extraction performance after 30 times
      use. Under the established optimum conditions, the limits of detection for DA, E,
      and NE were 7.4, 4.8, and 7.1 nmol L(-1), respectively, with the enhancement
      factor over 100 after MIP-SPME. The specific selectivity to three CAs was
      discovered with the developed MIP fibers compared with non-imprinted polymer
      (NIP) fiber. Finally, the MIP fibers were successfully applied for selective
      extraction of CAs in urine and serum samples with the relative recoveries ranging
      from 85% to 103%. The fabricated MIP-fibers were promising in preparation of
      biological samples in batch followed by CE-UV detection.

PMID- 22967552
TI  - Photoelectrocatalytic oxidation of formaldehyde using a Ti/TiO2 foil electrode.
      Application for its novel and simple photoelectrochemical determination.
AB  - It was firstly described, that a TiO(2) film modified titanium foil electrode
      (Ti/TiO(2)) shows an efficient photoelectrocatalytic activity towards
      formaldehyde oxidation in a phosphate buffer solution. Ti/TiO(2) foil electrode
      was prepared by anodizing Ti foil in aqueous solution. Also, this electrode was
      applied for the hydrodynamic photoamperometry measurement of formaldehyde in the
      optimum conditions (pH 7.0 as biological pH and bias potential 0.8 V vs.
      reference electrode). The photoelectrocatalytic oxidation photocurrent of the
      photoelectrode determined by photoamperometry method was linearly dependent on
      the formaldehyde concentration and the linearity range obtained was 6.70*10(-4)
      1.48*10(-2) mol L(-1). Detection limit was found to be 3.09*10(-4) mol L(-1)
      (2sigma).

PMID- 22967553
TI  - Fabrication of a tunable glucose biosensor based on zinc oxide/chitosan-graft
      poly(vinyl alcohol) core-shell nanocomposite.
AB  - A potentiometrically tuned-glucose biosensor was fabricated using core-shell
      nanocomposite based on zinc oxide encapsulated chitosan-graft-poly(vinyl alcohol)
      (ZnO/CHIT-g-PVAL). In a typical experiment, ZnO/CHIT-g-PVAL core-shell
      nanocomposite containing <20 nm ZnO nanoparticles was synthesized using wet
      chemical method. The glucose responsive bio-electrode, i.e., glucose
      oxidase/ZnO/chitosan-graft-poly(vinyl alcohol) (GOD/ZnO/CHIT-g-PVAL/ITO) was
      obtained by immobilization of glucose oxidase (GOD) onto the electrode made of
      resulting ZnO core-shell nanocomposite coated on the indium-tin oxide (ITO) glass
      substrate. The ZnO/CHIT-g-PVAL/ITO and GOD/ZnO/CHIT-g-PVAL electrodes were
      characterized with Fourier transform infrared spectroscopy (FTIR) and scanning
      electron microscopy (SEM), whereas ZnO/CHIT-g-PVAL size of core-shell
      nanoparticles were measured using transmission electron microscopy (TEM). The
      electrostatic interaction between GOD and ZnO/CHIT-g-PVAL provided the resulting
      tuned enzyme electrode with a high degree of enzyme immobilization and excellent
      lifetime stability. The response studies were carried out as a function of
      glucose concentration with potentiometric measurement. The GOD/ZnO/CHIT-g
      PVAL/ITO bioelectrode has showed a linear potential response to the glucose
      concentration ranging from 2 MUM to 1.2mM. The glucose biosensor exhibited a fast
      surface-controlled redox biochemistry with a detection limit of 0.2 MUM, a
      sensitivity of >0.04 V/MUM and a response time of three sec. ZnO/CHIT-g-PVAL core
      shell nanocomposite could be a promising nanomaterials for a range of enzymic
      biosensors.

PMID- 22967554
TI  - Enhanced host-guest electrochemical recognition of herbicide MCPA using a beta
      cyclodextrin carbon nanotube sensor.
AB  - An electrochemical sensor for the determination of the chlorophenoxy herbicide
      MCPA has been developed, based on a combination of multi-walled carbon nanotubes
      with incorporated beta-cyclodextrin and a polyaniline film modified glassy carbon
      electrode. The proposed molecular host-guest recognition based sensor has a high
      electrochemical sensitivity for the determination of MCPA. The electrochemical
      behaviour of MCPA at the chemically modified electrode was investigated in detail
      by cyclic voltammetry. The results indicate that the beta-CD/MWCNT modified
      glassy carbon electrode exhibits efficient electrocatalytic oxidation of MCPA
      with high sensitivity, stability and lifetime. The analytical characteristics of
      this film were used for the quantitative determination of MCPA in natural waters.
      Cyclic voltammetry in phosphate buffer solution at pH 6.0, allowed the
      development of a method to determine MCPA, without any previous steps of
      extraction, clean-up, or derivatization, in the range of 10-100 MUmol L(-1), with
      a detection limit of 0.99 MUmol L(-1) in water. The results were statistically
      compared with those obtained through an established high-performance liquid
      chromatography technique, no significant differences having been found between
      the two methods.

PMID- 22967555
TI  - Effective enrichment of cholangiocarcinoma secretomes using the hollow fiber
      bioreactor culture system.
AB  - The Northeastern region of Thailand is well known to have high incidence of bile
      duct cancer known as cholangiocarcinoma. So there is a continued need to improve
      diagnosis and treatment, and discovery of biomarkers for early detection of bile
      duct cancer should greatly improve treatment outcome for these patients. The
      secretome, a collection of proteins secreted from cells, is a useful source for
      identifying circulating biomarkers in blood secreted from cancer cells. Here a
      Hollow Fiber Bioreactor culture system was used for enrichment of
      cholangiocarcinoma secretomes, since this culture system mimics the dense three
      dimensional microenvironment of the tumor found in vivo. Two-dimensional
      fluorescence difference gel electrophoresis using a sensitive Fluor saturation
      dye staining, followed by LC/MS/MS, was used to compare protein expression in the
      secretomes of cells cultured in the Hollow Fiber system and cells cultured in the
      monolayer culture system. For the first time, the 2D-patterns of
      cholangiocarcinoma secretomes from the two culture systems could be compared. The
      Hollow Fiber system improved the quality and quantity of cholangiocarcinoma
      secreted proteins compared to conventional monolayer system, showing less
      interference by cytoplasmic proteins and yielding more secreted proteins.
      Overall, 75 spots were analyzed by LC/MS/MS and 106 secreted proteins were
      identified. Two novel secreted proteins (C19orf10 and cystatin B) were found only
      in the Hollow Fiber system and were absent from the traditional monolayer culture
      system. Among the highly expressed proteins, 22 secreted soluble proteins were
      enriched by 5 fold in Hollow Fiber system compared to monolayer culture system.
      The Hollow Fiber system is therefore useful for preparing a wide range of
      proteins from low-abundance cell secretomes.

PMID- 22967556
TI  - An amperometric bienzymatic cholesterol biosensor based on functionalized
      graphene modified electrode and its electrocatalytic activity towards total
      cholesterol determination.
AB  - Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently
      immobilized onto functionalized graphene (FG) modified graphite electrode.
      Enzymes modified electrodes were characterized using cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). FG accelerates the electron
      transfer from electrode surface to the immobilized ChOx, achieving the direct
      electrochemistry of ChOx. A well defined redox peak was observed, corresponding
      to the direct electron transfer of the FAD/FADH(2) of ChOx. The electron transfer
      coefficient (alpha) and electron transfer rate constant (K(s)) were calculated
      and their values are found to be 0.31 and 0.78 s(-1), respectively. For the free
      cholesterol determination, ChOx-FG/Gr electrode exhibits a sensitive response
      from 50 to 350 MUM (R=-0.9972) with a detection limit of 5 MUM. For total
      cholesterol determination, co-immobilization of ChEt and ChOx on modified
      electrode, i.e. (ChEt/ChOx)-FG/Gr electrode showed linear range from 50 to 300
      MUM (R=-0.9982) with a detection limit of 15 MUM. Some common interferents like
      glucose, ascorbic acid and uric acid did not cause any interference, due to the
      use of a low operating potential. The FG/Gr electrode exhibits good
      electrocatalytic activity towards hydrogen peroxide (H(2)O(2)). A wide linear
      response to H(2)O(2) ranging from 0.5 to 7 mM (R=-0.9967) with a sensitivity of
      443.25 MUA mM(-1) cm(-2) has been obtained.

PMID- 22967557
TI  - Identification of degradation products of phenylarsonic acid and o-arsanilic acid
      in contact with suspensions of soils of volcanic origin.
AB  - A set of organoarsenicals were identified in aqueous phenylarsonic acid (PA) and
      o-arsanilic acid (AA) solutions treated with soil of volcanic origin in batch
      systems. The transformation products were separated by liquid chromatography (RP
      LC) and identified with element selective inductively coupled plasma-mass
      spectrometry (ICP-MS) as well as molecular selective electrospray ionization-mass
      spectrometry (ESI-MS) detection after their HPLC separation. The identification
      of the main degradation products by means of ESI-MS, ESI-MS/MS and ESI-TOF-MS
      showed the occurrence of nitrophenylarsonic acid and methylphenylarsinic acid in
      the solutions containing AA and PA in contact with soils, respectively. Using
      irradiation of PA solution with visible light, new compounds related from PA
      appeared with increasing irradiation times which were identified as 4
      hydroxyphenylarsonic acid, 3-hydroxyphenylarsonic acid and 2-hydroxyphenylarsonic
      acid. Additionally, a dihydroxyphenylarsonic compound was identified as impurity
      of PA.

PMID- 22967558
TI  - Optimization of focused ultrasonic extraction of propellant components determined
      by gas chromatography/mass spectrometry.
AB  - A method for focused ultrasonic extraction of nitroglycerin, triphenyl amine and
      acetyl tributyl citrate presented in double-base propellant samples following by
      the gas chromatography/mass spectrometry analysis was developed. A face-centered
      central composite design of the experiments and response surface modeling was
      used for optimization of the time, amplitude and sample amount. The
      dichloromethane was used as the extractant solvent. The optimal extraction
      conditions with respect to the maximum yield of the lowest abundant compound
      triphenyl amine were found at the 20 min extraction time, 35% amplitude of
      ultrasonic waves and 2.5 g of the propellant sample. The results obtained under
      optimal conditions were compared with the results achieved with validated Soxhlet
      extraction method, which is typically used for isolation and pre-concentration of
      compounds from the samples of explosives. The extraction yields for acetyl
      tributyl citrate using both extraction methods were comparable; however, the
      yield of ultrasonic extraction of nitroglycerin and triphenyl amine was lower
      than using Soxhlet extraction. The possible sources of different extraction
      yields are estimated and discussed.

PMID- 22967559
TI  - Study of the heat stability of sunflower oil enriched in natural antioxidants by
      different analytical techniques and front-face fluorescence spectroscopy combined
      with Independent Components Analysis.
AB  - The aim of this study was to find objective analytical methods to study the
      degradation of edible oils during heating and thus to suggest solutions to
      improve their stability. The efficiency of Nigella seed extract as natural
      antioxidant was compared with butylated hydroxytoluene (BHT) during accelerated
      oxidation of edible vegetable oils at 120 and 140  degrees C. The modifications
      during heating were monitored by 3D-front-face fluorescence spectroscopy along
      with Independent Components Analysis (ICA), (1)H NMR spectroscopy and classical
      physico-chemical methods such as anisidine value and viscosity. The results of
      the study clearly indicate that the natural seed extract at a level of 800 ppm
      exhibited antioxidant effects similar to those of the synthetic antioxidant BHT
      at a level of 200 ppm and thus contributes to an increase in the oxidative
      stability of the oil.

PMID- 22967560
TI  - Development of a new aerosol phase extraction method for metal determination
      through inductively coupled plasma atomic emission spectrometry.
AB  - In this work, a new extraction method termed aerosol phase extraction has been
      developed for the first time. The new method was based on the nebulisation of the
      sample onto the extracting solution to maximize the contact surface. The
      influential parameters are: agitation time, chelating agent concentration and
      inorganic acid concentration. The method has been applied to the extraction of
      molybdenum with organophosphorus chelating agents such as tributyl phosphate
      (TBP) and bis(2-Ethylhexyl) phosphoric acid (D2EHPA) dissolved in n-hexane from
      aqueous hydrochloric and phosphoric acid solutions. In order to test the
      efficiency of the method, the aqueous phase has been analyzed by means of
      Inductively Coupled Plasma Atomic Emission Spectrometry. The extraction of
      molybdenum under aerosol phase was found to be faster than the conventional
      extraction method. Equilibrium time was shortened under aerosol phase extraction
      and molybdenum extraction yields were comparable, or better as compared to the
      conventional method.

PMID- 22967561
TI  - In-situ differential pulse anodic stripping voltammetry combined with hollow
      fiber-based liquid-three phase micro extraction for determination of mercury
      using Au-nanoparticles sol-gel modified Pt-wire.
AB  - A new method has been proposed based on hollow fiber-based liquid three-phase
      micro extraction and in-situ differential pulse anodic stripping voltammetry
      (DPASV) for the micro extraction and quantification of mercury(II) ions.
      Different factors affecting the liquid-three phases micro extraction, including
      organic solvent, pH of the donor and acceptor phases, concentration of the
      complexing agent, extraction time, and stirring rate were investigated and the
      optimal extraction conditions were established. Three microelectrodes designed
      and constructed for this study were inserted into the two ends of a hollow fiber
      inside the acceptor solution, and then voltammetric analysis was performed in
      situ during the extraction time. After 1600 s, final stable signal was used for
      the analytical applications. Under the optimized conditions, an enrichment factor
      of 277 was achieved and the relative standard deviation (R.S.D.) of the method
      was 6.2% (n=5). The calibration curve was obtained in the range of 0.2-30.0 nmol
      L(-1) Hg(II) with a reasonable linearity (R(2)>0.9880) and a limit of detection
      of 0.06 nmol L(-1). Finally, the applicability of the proposed method was
      evaluated by extraction and determination of mercury in real samples such as fish
      and rice.

PMID- 22967562
TI  - Absolute quantification for benzoic acid in processed foods using quantitative
      proton nuclear magnetic resonance spectroscopy.
AB  - The absolute quantification method of benzoic acid (BA) in processed foods using
      solvent extraction and quantitative proton nuclear magnetic resonance
      spectroscopy was developed and validated. BA levels were determined using proton
      signals (delta(H) 7.53 and 7.98) referenced to 2-dimethyl-2-silapentane-5
      sulfonate-d(6) sodium salt (DSS-d(6)) after simple solvent extraction from
      processed foods. All recoveries from several kinds of processed foods, spiked at
      their specified maximum Japanese usage levels (0.6-2.5 g kg(-1)) and at 0.13 g
      kg(-1) and 0.063 g kg(-1), were greater than 80%. The limit of quantification was
      confirmed as 0.063 g kg(-1) in processed foods, which was sufficiently low for
      the purposes of monitoring BA. The accuracy of the proposed method is equivalent
      to the conventional method using steam-distillation extraction and high
      performance liquid chromatography. The proposed method was both rapid and simple.
      Moreover, it provided International System of Units traceability without the need
      for authentic analyte standards. Therefore, the proposed method is a useful and
      practical tool for determining BA levels in processed foods.

PMID- 22967563
TI  - Automatic determination of copper by in-syringe dispersive liquid-liquid
      microextraction of its bathocuproine-complex using long path-length
      spectrophotometric detection.
AB  - The recently proposed concept of automatic in-syringe dispersive liquid-liquid
      microextraction was successfully applied to the determination of copper in
      environmental water samples. Bathocuproine was added to the organic phase as a
      selective reagent, resulting in the formation of a complex with copper.
      Dispersion was achieved by aspiration of the organic phase and then the watery
      phase into the syringe as rapidly as possible. After aggregation of the solvent
      droplets at the head of the syringe, the organic phase was pushed into a liquid
      waveguide capillary cell for highly sensitive spectrophotometric detection. The
      entire analytical procedure was carried out automatically on a multisyringe flow
      injection analysis platform and a copper determination was accomplished in less
      than 220 s. A limit of detection of 5 nmol L(-1) was achieved at an extraction
      efficiency >90% and a preconcentration factor of 30. A linear working range for
      concentrations of up to 500 nmol L(-1) and an average standard deviation of 7% in
      peak height were found. The method proved to be well-suited for the determination
      of copper in water samples, with an average analyte recovery of 100.6%.

PMID- 22967564
TI  - Development and validation of an enzyme-linked immunosorbent assay for the
      quantification of cytochrome 3A4 in human liver microsomes.
AB  - Little is known about the influence of hepatic pathologies on cytochrome P450
      (CYP) mediated drug metabolism in children. The determination of the abundance of
      the different isoforms in pediatric microsomes may provide valuable information
      on the mechanisms of possible changes in activity. Until now, western blotting
      was mostly used for abundance measurements, but this technique only provides semi
      quantitative data. Therefore, this study aimed to develop and validate an
      indirect ELISA for the quantification of the most important CYP isoform, CYP3A4,
      in human liver microsomes, using commercially available reagents. Samples,
      calibrators and validation samples were diluted to a final concentration of 10
      MUg microsomal protein/ml. A polyclonal antibody raised against the full length
      human protein was used as primary antibody; horseradish peroxidase conjugated
      secondary antibodies for detection. The assay was validated for sensitivity,
      working range and calibration, accuracy and precision. Amounts of CYP3A4 between
      2 and 300 pmol/mg microsomal protein could be quantified with a 5-parameter
      logistics function with 1/x weighting factor. Coefficients of variation of intra
      and inter assay variability were between 9.54 and 13.98% (16.34% at LLOQ), and
      between 10.51 and 14.55% (19.44% at LLOQ), respectively. The relative error (%RE)
      varied between -5.96 and 6.68% (11.53% at LLOQ), and the total error between
      11.93 and 21.23% (30.97% at LLOQ). The cross-reactivity of the method with human
      CYP2E1 showed to have no significant effect on the accuracy of the results.
      Successful analysis of five samples from an ongoing study demonstrated the
      usefulness of the method.

PMID- 22967565
TI  - Development and validation of a simple thermo-desorption technique for mercury
      speciation in soils and sediments.
AB  - An innovative technique for rapid identification and quantification of mercury
      (Hg) species in soils and sediments was developed using a direct mercury
      analyser. Speciation was performed by the continuous thermal-desorption of
      mercury species (temperature range 76-770  degrees C), in combination with atomic
      absorption spectrophotometry detection. Standard materials HgCl(2), Hg bound to
      humic acids and HgS were characterized; thermo-desorption curves of each material
      showed a well-resolved peak at specific temperature intervals: 125-225  degrees
      C, 100-250  degrees C and 225-325  degrees C, respectively. Certified reference
      materials (CRM) BCR((r)) 142R, RTC((r)) CRM 021, NRC((r)) MESS-3 and PACS-2 were
      tested. Although the CRM were not certified for Hg species, the sum of Hg species
      obtained was compared to the certified value for total Hg; recoveries were 92%,
      100%, 97%, and 95%, respectively. One sediment and three soil samples from
      mercury contaminated areas (total Hg concentrations 0.067-126 mg kg(-1)) were
      analysed as well. It was possible to compare peaks of thermo-desorption curves
      from the samples with those from standard materials and thereby distinguish
      different Hg species in solid samples. Generally, Hg was present as bound to
      chloride or humic substances. The precision was satisfactory, as reflected by the
      relative standard deviations determined for standards and certified reference
      materials (<11%; n=10).

PMID- 22967566
TI  - Analysis of rare earth elements in seawater by inductively coupled plasma mass
      spectrometry after pre-concentration using TSKTM-HD-MW-CNTs (highly dispersive
      multi-walled carbon nanotubes).
AB  - This study aimed to identify easy-to-use multi-walled carbon nanotubes (MW-CNTs)
      having a high capacity to adsorb metals and thereby expand the usability of these
      materials as a solid-phase adsorbent for the analysis of trace metals in
      seawater. High-dispersion-type MW-CNTs had the highest metal binding capacity
      (70.8+/-5.1 mg/g for La) after a strong acid oxidation procedure, possibly
      because the high dispersibility resulted in a more complete reaction than with
      highly crystalline types. Because the high-dispersion-type MW-CNTs leaked from a
      conventional column, they were attached to polymer beads (TSKTM) (pore diameter
      about 20 MUm). Flow rate, pH, and volume of the seawater sample, as well as
      eluent type and volume, were optimized to obtain 0.01-0.16 pg/mL detection limits
      for rare earth elements (REEs). In addition, normalized patterns for samples
      collected from the East Sea showed characteristic features of REEs in seawater,
      i.e., a negative Ce anomaly, low atomic number REE (LREE) depletion, and high
      atomic number REE (HREE) enrichment.

PMID- 22967567
TI  - MicroRNA detection using lateral flow nucleic acid strips with gold
      nanoparticles.
AB  - In this study, the tested microRNA and the detection probe perfectly match with
      the capture probe instead of the traditional sandwich methods in which the tested
      oligonucleotide matches with the detection and capture probes. To avoid non
      specific signals, mung-bean nuclease, a single-strand-specific nuclease,
      catalyzes the degradation of the capture probe if there is no tested miRNA in the
      samples. The gold nanoparticles conjugate the thiol-DNA as the detection probe
      and the biotin-single strand DNA serves as the capture probe. The avidin-biotin
      Au-sample complex is captured by the anti-avidin antibody immobilized on a flow
      strip. The detection and quantification of the gold nanoparticle signal indicate
      the existence and quantity of the target miRNA. One fmol and five amol of the
      synthetic microRNA were detected without and with the silver enhancement,
      respectively. This highly sensitive and specific assay takes about 70 min after
      the RNA purification and preparation. It is simple, convenient, fast, and
      suitable for point-of-care.

PMID- 22967568
TI  - Simultaneous determination of pesticides and 5-hydroxymethylfurfural in honey by
      the modified QuEChERS method and liquid chromatography coupled to tandem mass
      spectrometry.
AB  - Nowadays, bee products are being produced in an environment polluted by different
      sources of contamination, such as pesticides, which can be transported by honey
      bees to the hive and incorporated into honey. In addition, the increasing
      consumption of honey has demanded efficient quality control for this product. In
      this study, the determination of the pesticides fipronil, imidacloprid,
      thiamethoxam, dimethoate, carbendazin, tebuconazole, amitraz, tau-fluvalinate and
      5-hydroxymethylfurfural (HMF) which are used as indicators of honey quality, was
      carried out simultaneously. For the sample preparation, the optimized QuEChERS
      method was used and the determinations were done by LC-APCI-MS/MS. The LOQs of
      the method ranged between 0.005 and 1.0 mg kg(-1). For the recovery calculations
      and method evaluation a working curve was drawn. All the analytical curves showed
      r values higher than 0.99. The recoveries ranged between 70% and 112%, with RSD
      lower than 20% for all compounds. The matrix effect was evaluated, and most of
      the compounds showed signal enrichment. The applicability of the method for honey
      from different flowers was verified, and the method showed robustness and
      recoveries in the range 70-120% established for all compounds in samples
      belonging to different blossoms. HMF was detected in all samples, with
      concentrations ranging between 4.6 and 51.7 mg kg(-1); it was below the maximum
      concentration allowed by the legislation.

PMID- 22967569
TI  - Near infrared dye indocyanine green doped silica nanoparticles for biological
      imaging.
AB  - Indocyanine green (ICG) is an FDA-approved near infrared (NIR) fluorescent dye
      used in clinical imaging. However, its applications remain limited due to its
      short half-life, nonspecific plasma binding, optical instability, and poor
      aqueous stability. Dye doped silica nanoparticles provide an effective barrier in
      keeping the dye away from the surrounding environment, but ICG cannot be
      encapsulated into silica easily by conventional methods. In this study, ICG
      molecules ion-paired with a cationic polymer polyethylenimine (PEI) were
      successfully encapsulated into a silica matrix to form ICG doped silica
      nanoparticles by using the Stober method. Pairing with PEI reduced self-quenching
      of fluorescence by preventing the aggregation of ICG molecules in silica
      nanoparticles. Dye leakage was also reduced to the level of 3-6% loss in 5 days.
      NIR fluorescence images of ICG doped silica NPs below a 2.0 cm thick porcine
      muscle sample illuminated by NIR light were obtained.

PMID- 22967570
TI  - Modification of coral-like SnO2 nanostructures with dense TiO2 nanoparticles for
      a self-cleaning gas sensor.
AB  - A coral-like SnO(2) nanostructure densely-modified with TiO(2) nanoparticles was
      reported for developing a self-cleaning gas sensor. The density of the TiO(2)
      nanoparticles in the TiO(2)/SnO(2) nanocomposites can be greatly improved via a
      plasma-based modification (PM) on SnO(2)/carbonaceous precursors before
      introducing Ti sources. In gas-sensing measurements, benzene and toluene were
      employed as target analytes. The results show that the gas sensor based on the
      TiO(2)/SnO(2) nanostructures with PM exhibits a remarkably improved stability
      after detecting for many cycles compared with the ones based on TiO(2)/SnO(2)
      without PM and pure SnO(2) nanostructures. The mechanism for the stable
      performance has been demonstrated from the self-cleaning degradation of TiO(2)
      nanoparticles towards the adsorbed organic species. Furthermore, the recognizable
      ability towards targets was also investigated by using some algorithmic
      recognition methods including principal component analysis (PCA) and nonnegative
      matrix factorization (NMF). The fascinating gas-sensing properties including
      enhanced stability, sensitivity, and recognizable ability enable the presented
      TiO(2)/SnO(2) nanocomposites to be a promising candidate for fabricating self
      cleaning gas sensor which can be applied for detecting environmental gas
      contaminants.

PMID- 22967571
TI  - Sensitive determination of chromium (VI) based on the inner filter effect of
      upconversion luminescent nanoparticles (NaYF4:Yb3+, Er3+).
AB  - A new method was developed for selective and sensitive determination of trace
      chromium (VI) based on the inner filter effect (IFE) of upconversion luminescent
      nanoparticles (NaYF(4):Yb(3+), Er(3+)) as fluorescence probes. In this study,
      water-soluble and well dispersible upconversion luminescent nanoparticles
      (NaYF(4):Yb(3+), Er(3+)) were firstly synthesized by hydrothermal method, and
      characterized by transmission electron microscopy (TEM) and luminescence
      spectroscopy. And then, the IFE method was established for determination of
      chromium (VI). The principle of this assay is based on the complementary overlap
      of the green emission band of nanoparticles (NaYF(4):Yb(3+), Er(3+)) with the
      absorption spectrum of a pink chelate complex (Cr(III)-diphenylcarbazone), which
      was generated by the quantitative reaction between diphenylcarbazide (DPC) and
      Cr(VI) in mineral acid solution. Under the optimal condition, the decrease in the
      upconversion luminescent nanoparticles was proportional to the concentration of
      chromium (VI) due to IFE. The linear range is 0.070-10.0*10(-6) mol L(-1) Cr(VI),
      and the limit of detection (3sigma) is 2.40*10(-8) mol L(-1) Cr(VI). The method
      described here is sensitive than the method of spectrophotometry. This assay was
      used in the determination of Cr(VI) in water samples.

PMID- 22967572
TI  - A novel beta-Cyclodextrin-QDs optical biosensor for the determination of
      amantadine and its application in cell imaging.
AB  - In this paper, a novel optical biosensor for amantadine (AD) determination has
      been constructed successfully based on the fluorescence resonance energy transfer
      (FRET) between water-soluble beta-Cyclodextrin (beta-CD)-functionalized CdTe
      quantum dots (QDs) and Rhodamine B (RB). RB could enter the cavity of beta-CD by
      hydrophobic interaction, and the process of FRET between QDs and RB occurred.
      However, the process of FRET was switched off with the addition of AD, due to its
      larger hydrophobic association constant with beta-CD than that of RB. The
      fluorescence intensity of CdTe QDs (donor) would increase gradually with the
      increasing concentration of AD, which shown a good linear relationship in the
      range of 1*10(-5)-1.6*10(-4) mol/L with a correlation coefficient R(2)=0.998. We
      also obtained a satisfactory result using this spectrophotometric method for the
      determination of AD in pharmaceutical formulation. Furthermore, beta-CD
      functionalized CdTe QDs with AD in the cavity were incubated with target HepG2
      cells and could be observed in the cytoplasm of cells. The beta-CD-functionalized
      CdTe QDs could act as a visible biomarker for AD in cancer cells fluorescence
      imaging, which presents a potential application in biomedical field.

PMID- 22967573
TI  - High-throughput Ru(III) analysis using the hydrothermal flow reactor-mediated FIA
      by the extreme acceleration of Ru(III) complexation with 1,10-phenanthroline.
AB  - A new type of flow injection analysis (FIA) combined with a high-temperature
      reactor maintained at 100-400  degrees C, namely hydrothermal flow injection
      analysis (HT-FIA), has been successfully applied to high throughput determination
      of Ru(III) on the basis of a conventional chromogenic reaction with 1,10
      phenothroline (phen). Although this classical chromogenic reaction using phen is
      sensitive and selective for Ru(III), the complex formation of Ru(phen)(3)
      requires 2 h. The acceleration using HT-FIA is extraordinary high so that the
      determination reaction of Ru(III) was successfully shortened to 5 s at 150 
      degrees C, where the analytical procedure was accelerated more than 1000-fold.
      This enabled a high-throughput analysis of Ru(III) with 100 MUL sample, of which
      at least 10 samples can be analyzed within 10 min. The detection limit of Ru(III)
      determined on the basis of 3 times of standard deviation was 5.3*10(-7) M (53
      pmol or 5.4 ng Ru in 100 MUL sample). The present study emphasizes the importance
      of the revival of classical chromogenic reactions, which are potentially valuable
      but not regarded anymore as useful because they are time-consuming and tedious,
      to fit for the demand for environmentally harmless analytical techniques.

PMID- 22967574
TI  - A new derivatization approach for the rapid and sensitive analysis of
      brassinosteroids by using ultra high performance liquid chromatography
      electrospray ionization triple quadrupole mass spectrometry.
AB  - In this work, a new labeling reagent, 2-bromopyridine-5-boronic acid (BPBA), was
      introduced to derivatize brassinosteroids (BRs). The BPBA not only provided a
      very simple and rapid labeling procedure, but also remarkably increased the
      detection sensitivity of BRs. Based on this new labeling reaction, a rapid and
      sensitive method for BRs' analysis in Arabidopsis thaliana was established by
      using the ultra high performance liquid chromatography-electrospray ionization
      triple quadrupole mass spectrometry (UHPLC-ESI-QqQ-MS). The extraction and
      purification procedure of the plant sample was also simplified and improved in
      this work. Good linearities were obtained for three BRs with the determination
      coefficients (R(2)) about 0.9999. The limits of detection (S/N=3) for three BRs
      were found to be 2.00-8.00 ng/L while the limits of quantification (S/N=10) were
      6.00-23.0 ng/L. The RSD % for all three samples are lower than 8.67% (n=5). The
      recoveries of three BRs spiked in A. thaliana samples were from 76.9% to 86.1%.
      Using this method, the endogenous 0.055 ng/g fresh weight (FW) 24-epiBR and 0.070
      ng/g (FW) 28-epihomoBR were successfully detected from only 2g A. thaliana
      plants.

PMID- 22967575
TI  - Confirmation of brand identity of a Trappist beer by mid-infrared spectroscopy
      coupled with multivariate data analysis.
AB  - Authentication of foods is of importance both to consumers and producers for e.g.
      confidence in label descriptions and brand protection, respectively. The
      authentication of beers has received limited attention and in most cases only
      small data sets were analysed. In this study, Fourier-transform infrared
      attenuated total reflectance (FT-IR ATR) spectroscopy was applied to a set of 267
      beers (53 different brands) to confirm claimed identity for samples of a single
      beer brand based on their spectral profiles. Skewness-adjusted robust principal
      component analysis (ROBPCA) was deployed to detect outliers in the data.
      Subsequently, extended canonical variates analysis (ECVA) was used to reduce the
      dimensionality of the data while simultaneously achieving maximum class
      separation. Finally, the reduced data were used as inputs to various linear and
      non-linear classifiers. Work focused on the specific identification of Rochefort
      8 degrees  (a Trappist beer) and both direct and indirect (using an hierarchical
      approach) identification strategies were studied. For the classification problems
      Rochefort vs. non-Rochefort, Rochefort 8 degrees  vs. non-Rochefort 8 degrees 
      and Rochefort 8 degrees  vs. Rochefort 6 degrees  and 10 degrees , correct
      prediction abilities of 93.8%, 93.3% and 97.3%, respectively were achieved.

PMID- 22967576
TI  - A fiber-optic sensor to detect volatile organic compounds based on a porous
      silica xerogel film.
AB  - Fiber-optic sensors are increasingly used for the determination of volatile
      organic compounds (VOCs) in air matrices. This paper provides experimental
      results on the sensitivity of a fiber-optic sensor that uses a film of a porous
      silica xerogel as the sensing element. This film was synthesized by the sol-gel
      process and affixed to the end of the optical fiber by the dip-coating technique.
      This intrinsic sensor works in reflection mode, and the transduction takes place
      in the light that travels through the core of the fiber. The VOCs included in
      this research cover a wide range of compounds with different functional groups
      and polarities. The highest sensitivity was for 2-propanol (13.1+/-1.4 M(-1) nm(
      1)), followed by toluene (11.4+/-1.4 M(-1) nm(-1)), and 1-butylamine (9.5+/-0.4
      M(-1) nm(-1)). Acetone and cyclohexane had the lowest sensitivity of all studied
      VOCs. Limits of detection varied between 9.1*10(-5) M for 1-butylamine and
      1.6*10(-3) M for ethanol. Silanol groups on the xerogel surface act as weak acids
      and interact strongly with molecules that contain OH groups like alcohols, pi
      electrons like toluene, or a lone pair of electrons like toluene. Stronger
      interaction of methanol and ethanol with the silanol groups on the film led to
      some irreversible adsorption of these analytes at room temperature.

PMID- 22967577
TI  - Characterization and application of molecular binary mixed molecular micelles of
      sodium 10-undecenyl sulfate and sodium N-undecenyl leucinate as pseudostationary
      phases in micellar electrokinetic chromatography.
AB  - Poly (sodium 10-undecenyl sulfate) (poly SUS), poly (sodium 10-undecenyl
      leucinate) (poly SUL), and their five molecular binary mixed micelles with varied
      SUS:SUL composition were prepared. The purity of these molecular micelles was
      confirmed by elemental analysis. Their partial specific volume, aggregation
      number, methylene selectivity, polarity, phase ratio, mobility, and elution
      window values were determined using a variety of analytical techniques. These
      molecular micelles were then evaluated as pseudostationary phases in micellar
      electrokinetic chromatography (MEKC) for separation of benzene derivatives with a
      wide range of chemical properties. Elemental analysis results reveal that the
      ratio of the two surfactants in the binary mixture does not change significantly
      during the polymerization process. Poly SUS was found to have the lowest partial
      specific volume and it increases gradually with an increase of SUL mole fraction.
      Poly SUL was found to provide the most hydrophobic environment for test solutes.
      Based on the retention results, the strength of interaction between the molecular
      micelles and the analytes was found to follow the following order: NHB>HBA>HBD.
      This order indicates that the hydrophobic interaction plays a major role in
      retention of benzene derivatives.

PMID- 22967578
TI  - Fast determination of cations in honey by capillary electrophoresis: a possible
      method for geographic origin discrimination.
AB  - This study reports the development and validation of a fast capillary
      electrophoresis method for cation determination in honey samples and the
      classification of honey by geographical origin using Principal Components
      Analysis (PCA). The background electrolyte (BGE) was optimized using the
      Peakmaster((r)) software, which evaluates the tendency of the analytes to undergo
      electromigration dispersion and the BGE buffer capacity and conductivity. The
      final BGE composition was defined as 30 mmol L(-1) imidazole, 300 mmol L(-1)
      acetic acid and 140 mmol L(-1) Lactic acid, at pH 3,0, and the separation of
      K(+), Na(+), Ca(2+), Mg(2+) and Mn(2+) using Ba(2+) as the internal standard was
      achieved in less than 2 min. The method showed satisfactory results in terms of
      linearity (R(2)>0.999), the detection limits ranged from 0.27-3.17 mg L(-1) and
      the quantification limits ranged from 0.91-10.55 mg L(-1). Precision measurements
      within 0.55 and 4.64%RSD were achieved and recovery values for the analytes in
      the honey samples ranged from 93.6%-108.6%. Forty honey samples were analyzed to
      test the proposed method. These samples were dissolved in deionized water and
      filtered before injection. The CE-UV reliability in the cation analysis in the
      real sample was compared statistically with ICP-MS methodology. No significant
      differences were found, with a 95% confidence interval between the methodologies.
      The PCA showed that the cumulative variance for the first two principal
      components explain more than 85% of the variability of the data. The analytical
      data suggest a significant influence of the geographical origin on the mineral
      composition.

PMID- 22967579
TI  - Characterizing natural colloidal/particulate-protein interactions using
      fluorescence-based techniques and principal component analysis.
AB  - Characterization of the interactions between natural colloidal/particulate- and
      protein-like matter is important for understanding their contribution to
      different physiochemical phenomena like membrane fouling, adsorption of bacteria
      onto surfaces and various applications of nanoparticles in nanomedicine and
      nanotoxicology. Precise interpretation of the extent of such interactions is
      however hindered due to the limitations of most characterization methods to allow
      rapid, sensitive and accurate measurements. Here we report on a fluorescence
      based excitation-emission matrix (EEM) approach in combination with principal
      component analysis (PCA) to extract information related to the interaction
      between natural colloidal/particulate- and protein-like matter. Surface plasmon
      resonance (SPR) analysis and fiber-optic probe based surface fluorescence
      measurements were used to confirm that the proposed approach can be used to
      characterize colloidal/particulate-protein interactions at the physical level.
      This method has potential to be a fundamental measurement of these interactions
      with the advantage that it can be performed rapidly and with high sensitivity.

PMID- 22967580
TI  - A novel molecular probe sensing polynuclear hydrolyzed aluminum by chelation
      enhanced fluorescence.
AB  - A novel molecular probe (P2) sensing polynuclear hydrolyzed aluminum by chelation
      enhanced fluorescence was described, which was prepared from 1,1'-(1,4
      phenylene)bis(7-methyl-1,3,5-octanetrione) and 2-aminomethylpyridine. P2 showed a
      strong fluorescence response to Al(III) when excited by the optimized wavelength
      of 400 nm and the lambda(max,em) at 505 nm indicated a hypsochromic shift of 11
      nm to that of free P2, but Cu(II) was observed to quench the fluorescence
      intensity to nearly zero. The P2-Al(III) complex indicated the best fluorescence
      response at a pH near 7 and there might be a relevance to the amphoteric property
      of the aluminum hydroxide. The emission intensity at 505 nm continued to increase
      until the mole ratio of [Al(III)]/[P2] reached a value of 13 and no stoichiometry
      was observed during the process, which implied that the sensing target of the P2
      probe was not the free aluminum ion but the polynuclear hydrolyzed aluminum. The
      binuclear hydrolyzed aluminum compounds were selected as model target molecules
      to simulate the energy-minimized structure of the P2-Al(III) complex to confirm
      the CHEF mechanism. The enhanced fluorescent images of HeLa cells incubated with
      1 MUM P2 and 5 MUM Al(III) were obtained.

PMID- 22967581
TI  - Carbon nanodots sensitized chemiluminescence on peroxomonosulfate-sulfite
      hydrochloric acid system and its analytical applications.
AB  - In the present work, new water-soluble fluorescent carbon nanodots (C-dots) were
      prepared in a facile microwave pyrolysis approach in minutes by combining glycine
      and polyethylene glycol 200 (PEG 200). Transmission electron microscopy (TEM)
      measurements showed that the resulting C-dots had diameters of about 3 nm. (13)C
      NMR spectra further confirmed the presence of carbons (sp(2) and sp(3))
      indicating a nanocrystalline core of the resulting C-dots with hydroxyl of PEG
      200 covered outside. It was discovered that the prepared C-dots could
      dramatically enhance the chemiluminescence (CL) intensity of potassium
      peroxomonosulfate-sodium sulfite-hydrochloric acid (PSHA) reactions. UV-vis
      absorption and photoluminescence (PL) spectra indicated that the C-dots
      sensitized enhancements originated from their energy transfer and electron
      transfer annihilation effects on the CL system. When the concentration of C-dots
      was 4*10(-5) M, and those of KHSO(5), Na(2)SO(3) and HCl were 1*10(-2) M, an
      excellent performance was obtained. The C-dots sensitized CL system was
      successfully applied to the determination of aliphatic primary amines in real
      water samples with satisfactory results.

PMID- 22967582
TI  - Amperometric sensors based on sawdust film modified electrodes: application to
      the electroanalysis of paraquat.
AB  - Natural or sodium hydroxide treated Ayous sawdusts were used to prepare thin film
      electrodes (denoted respectively as PSTFE and SSTFE). The sensors obtained
      exhibit good mechanical stability and a wide electrochemical potential range.
      Their electrochemical characterization revealed that they present a good capacity
      to accumulate cations, but are not useful for the electroanalysis of anions. In
      all cases, the signals were more intense and well defined on SSTFE compared to
      PSTFE. When applied to the electroanalysis of paraquat, a significant improvement
      of the current intensities was obtained on these electrodes compared to the bare
      glassy carbon electrode. The diffusion of this compound through the film which is
      the main process governing the electrochemical reaction at the electrode surface,
      is 2.2 times more important with SSTFE compared to PSTFE. After the optimization
      of the detection parameters, calibration curves were obtained in the
      concentration range 0.1-0.725 MUmol L(-1) for PSTFE and 0.05-0.6 MUmol L(-1) for
      SSTFE. The detection limits determined for a signal/noise ratio=3 are 5.49*10(-9)
      mol L(-1) for PSTFE and 3.02*10(-9) mol L(-1) for SSTFE.

PMID- 22967583
TI  - Electrochemical determination of NADH based on MPECVD carbon nanosheets.
AB  - Characterization and application of carbon nanosheets (CNSs) grown by microwave
      plasma enhanced chemical vapor deposition (MPECVD) have been investigated for the
      electrochemical biosensor. The as-grown CNS films possess a porous structure with
      a large amount of graphene edges which most of them are less than 2 nm in
      thickness, as confirmed by scanning and transmission electron microscopes.
      "Surface-sensitive" probe, Fe(CN)(6)(3-/4-), exhibits that the original CNSs have
      faster electron transfer than glassy carbon electrode, owing to much more edge
      plane sites on the original CNS surface. "Oxygen-sensitive" probe, Fe(3+/2+) also
      confirmed that the oxygen species in the CNS film can improve its electrochemical
      activity. The modified electrode by MPECVD CNS films has been used to detect NADH
      for the first time. The CNSs with many graphene edges efficiently catalyse the
      oxidation of NADH at 0.336 V. The biosensor linearly responds to NADH in the
      range of 0-500 MUM (R=0.99665), the sensitivity of the electrode is 85.8 mA M(-1)
      or 715 mA M(-1) cm(-2), and the detection limit of NADH is about 0.44 MUM
      (S/N=3). The biosensor also displays excellent stability for NADH detection and
      good selectivity in the interference from ascorbic acid.

PMID- 22967584
TI  - Application of a column classification method in a selectivity study involving
      caffeine and its related impurities.
AB  - In this paper a comparative study of RP-LC column selectivity as obtained by the
      classification method of the Katholieke Universiteit Leuven (KUL method) and the
      selectivity obtained in real pharmaceutical analysis is reported. The separation
      of caffeine and its respective impurities was performed on 35 brands of
      stationary phases in accordance with the method prescribed in the European
      Pharmacopoeia (Ph. Eur.). Evaluation concerned the probability of appropriate
      column selection related to the selection of two different stationary phases for
      reference. The comparison was based on the traditional correlation of the F
      values with the results of a system suitability test (SST) for the columns, as
      well as an application of a factor analysis (FA) for graphical visualisation of
      the differences and similarities between the stationary phases established
      against four test chromatographic parameters provided by the KUL method and the
      retention parameters of the compounds of interest describing the column
      performance test. The obtained results confirmed that the class of the stationary
      phases selected according to the chromatographic test parameters gave comparable
      separation for caffeine and its impurities.

PMID- 22967585
TI  - Pleurotus eryngii immobilized Amberlite XAD-16 as a solid-phase biosorbent for
      preconcentrations of Cd2+ and Co2+ and their determination by ICP-OES.
AB  - This article reports a method that is used for the preconcentration and
      determination of Cd(2+) and Co(2+) in vegetables, using Pleurotus eryngii
      immobilized Amberlite XAD-16 as a solid-phase biosorbent. The concentrations of
      metals were determined by inductively coupled plasma-optical spectrometry (ICP
      OES). Critical parameters, such as the pH of the solution, flow rate, the amount
      of biosorbent, type and volume of eluent, and the sample volume, that affect the
      solid-phase extraction (SPE) procedure were optimized. The optimum extraction
      conditions were determined as being a pH of 6.0 for Cd(2+) and of 5.0 for Co(2+);
      a sample flow rate of 2.0 mL min(-1); 200.0mg of biosorbent; and 5.0 mL of 1.0
      mol L(-1) HCl as eluent. The capacities of the biosorbent for metal uptake were
      found to be 11.3 and 9.8 mg g(-1) for Cd(2+) and Co(2+) ions, respectively. Limit
      of quantitations (LOQs) were found to be 0.67 and 0.82 ng mL(-1), respectively,
      for Cd(2+) and Co(2+). The linear working curves were observed to be in the
      linear range from 1.0 to 50.0 ng mL(-1), and possessed high correlation
      coefficients. The use of the SPE method showed 50.7- and 35.7-fold improvements
      in the sensitivities of ICP-OES. The developed method was successfully applied to
      NCS ZC-73014 (a certified reference tea sample). Relative standard deviations
      (RSD) were lower than 5.0%. The Cd(2+) and Co(2+) concentrations in the different
      parts (leave, root, stem, and fruit) of purslane, onion, rocket, okra, and
      aubergine were determined after microwave digestion and solid-phase extraction by
      P. eryngii immobilized on Amberlite XAD-16.

PMID- 22967586
TI  - Multi-walled carbon nanotube modified with 1-buthyl 3-methyl imidazolium
      hexaflouro phosphate supported on sawdust as a selective adsorbent for solid
      phase extraction of Bi(III).
AB  - Multi-walled carbon nanotube (MWCNT) was dispersed and loaded with 1-buthyl 3
      methyl imidazolium hexaflouro phosphate ([BMIM]PF(6)), supported on sawdust and
      used as a new adsorbent for preconcentration of trace amount of bismuth. In this
      method, Bi(III) ions are retained by the adsorbent in a column after formation of
      negative complex with iodide. BiI(4)(-) complexes are retained on MWCNT
      [BMIM]PF(6) through the electrostatic interactions with positive charge of
      imidazolium ion. The adsorbed complex is eluted from the column with a solution
      of nitric acid and determined by flame atomic absorption spectrometry (FAAS). The
      effect of various parameters, such as pH, sample volume, concentration and volume
      of nitric acid as eluent, iodide concentration in sample solution, and
      interfering ions was investigated in order to achieve highest sensitivity. The
      calibration graph was linear in the range of 4-300 ng mL(-1) for Bi(III) in the
      initial solution. The limit of detection based on 3S(b) was 2.3 ng mL(-1) for
      Bi(III). The relative standard deviation for ten replicate measurements of 20 and
      80 ng mL(-1) was 2.3 and 0.98%, respectively. The method was applied to the
      determination of Bi(III) ions in river water, tap water and drug samples.

PMID- 22967587
TI  - Magnetic graphene nanosheets based electrochemiluminescence immunoassay of cancer
      biomarker using CdTe quantum dots coated silica nanospheres as labels.
AB  - A highly sensitive electrochemiluminescence (ECL) immunosensor for the detection
      of prostate specific antigen (PSA) was designed using biofunctionalized magnetic
      graphene nanosheets (G@Fe(3)O(4)) as immunosensing probes and CdTe quantum dots
      coated silica nanospheres (Si/QDs) as signal amplification labels. In this work,
      a sandwich-type immunosensor was fabricated, which was assembled on the surface
      of indium tin oxide glass (ITO). The analyte was detected in a home-made flow
      injection ECL (FI-ECL) cell through the immunosensor. Owing to the signal
      amplification of G@Fe(3)O(4) composite and Si/QDs, the ECL measurement showed a
      great increase in detection signals compared with the unamplified method. Under
      optimal conditions, a wide detection range (0.003-50 ng mL(-1)) and a low
      detection limit (0.72 pg mL(-1)) were obtained through the sandwich-type
      immunosensor. The proposed strategy successfully demonstrated a reproducible,
      specific, and potent method that can be expanded to detect other proteins.

PMID- 22967588
TI  - A new approach to determine salicylic acid in human urine and blood plasma based
      on negative electrospray ion mobility spectrometry after selective separation
      using a molecular imprinted polymer.
AB  - This paper deals with a method based on negative electrospray ionization ion
      mobility spectrometry (ESI-IMS) as a detection technique. The method was used to
      determine the salicylic acid in human urine and plasma after selective separation
      of salicylic acid (SA) via molecular imprinted polymer (MIP). The ion mobility
      spectrum of salicylic acid in negative mode and the reduced mobility value for
      its ion peak is reported in this paper for the first time. In order to combine
      the technique with negative ESI-IMS, suitable experimental conditions related to
      MIP (e.g., Soxhlet extraction) were selected. The method was exhaustively
      validated in terms of sensitivity, imprinting factor, enrichment factor, and
      sorption capacity. The linear dynamic range of 0.02-2.00 MUg mL(-1) and the
      relative standard deviation (RSD) below 6% were obtained for the analysis of SA
      through this method. The average recovery was calculated about 92% for the
      analyzed drug. Finally, human urine and plasma were analyzed and the feasibility
      of the proposed method was successfully verified by the efficient clean-up of the
      samples using MIP separation before the analysis by ESI-IMS.

PMID- 22967589
TI  - Fast simultaneous determination of BHA and TBHQ antioxidants in biodiesel by
      batch injection analysis using pulsed-amperometric detection.
AB  - We report the first amperometric method for the simultaneous determination of
      butylated hydroxyanisole (BHA) and tert-butylhydroquinone (TBHQ) in biodiesel
      using batch-injection analysis (BIA) coupled to pulsed-amperometry. A sequence of
      potential pulses was selected in order to detect TBHQ and BHA separately in a
      single injection step at a glassy-carbon electrode. Samples were diluted in 50%
      v/v hydroethanolic solution with 0.1 mol L(-1) HClO(4) (supporting electrolyte)
      before injection using an electronic pipette. The method is highly precise
      (RSD<1%, n=10), fast (170 injections h(-1)), accurate (recovery between 100 and
      110%), presents low detection limits (73 and 75 nmol L(-1) BHA and TBHQ,
      respectively), and can be easily adapted for on-site determinations.

PMID- 22967590
TI  - Urine iodide determination by ion-pair reversed-phase high performance liquid
      chromatography and pulsed amperometric detection.
AB  - A sensitive and specific ion-pair reversed-phase high performance liquid
      chromatography (HPLC) method for urinary iodine analysis is described. This
      method is based on pulsed amperometric detection (PAD) using a silver working
      electrode (HPLC-PAD), which improves peak shape, electrode stability as well as
      linearity and reproducibility. A two-step extraction process consisting of solid
      phase extraction (SPE) and liquid-liquid extraction with dichloromethane was
      added in order to improve sample purification which is essential with the use of
      PAD. Treated samples were eluted on a C18 column, using a phosphate buffer
      containing ion-pairing reagent tetrabutylammonium and 5% MeOH. The calibration
      standard curves were linear up to 500 MUg/L and within-run and between-run
      coefficients of variation (CVs) were <6% with the quantification limit fixed at 6
      MUg/L. Accuracy, expressed as recovery, ranged from 94% to 104%. Comparison with
      the Technicon AutoAnalyzer acid digestion (AA) method resulted in a high
      correlation (r=0.9916). Due to a low quantification limit and high sample
      throughput, the proposed technique appears suitable for both epidemiological and
      clinical follow-up studies.

PMID- 22967591
TI  - Gold nanoparticle-biotinylated liposome hybrids as analytical reagents for biotin
      determination using a competitive assay and resonance light scattering detection.
AB  - The preparation of hybrid nanostructures formed by gold nanoparticles (AuNPs)
      into biotinylated liposomes and their analytical application are presented. The
      surface of negatively charged AuNPs was modified with 1-dodecanethiol and the NPs
      were encapsulated into biotinylated liposomes using the rapid solvent evaporation
      method. Liposomes were resized by both mechanical shaking and ultrasound
      treatments and filled liposomes were separated from empty liposomes using sucrose
      density gradient centrifugation. The analytical usefulness of AuNP-liposome
      hybrids as amplification probes for biotin determination was checked using the
      competitive affinity reaction based on the avidin-biotin interaction and
      biotilynated phospholipids for the synthesis of the liposome hybrids. The method
      was automatized using a flow system and measuring the resonance light scattering
      signal. The dynamic range of the calibration graph was 0.001-20 MUg mL(-1),
      (r(2)=0.9998, n=14), with a detection limit of 0.3 ng mL(-1). The precision,
      expressed as relative standard deviation (RSD%), was lower than 5% and the
      sampling frequency was 9 h(-1). The approach has been applied to the
      determination of biotin in food samples, with recovery values ranging between
      88.2 and 105.2%.

PMID- 22967592
TI  - BioElectronic Tongue for the quantification of total polyphenol content in wine.
AB  - This work reports the application of a BioElectronic Tongue (BioET) in the
      estimation of polyphenol content in wine. The approach used an array of enzyme
      biosensors capable of giving a wide and complete response of the analyzed
      species, plus a chemometric processing tool able to interpret the chemical
      signals and extract meaningful data from the complex readings. In our case, the
      proposed BioET was formed by an array of four voltammetric enzymatic biosensors
      based on epoxy-graphite composites, one blank electrode and the other three bulk
      modified with tyrosinase and laccase on one side, and copper nanoparticles on the
      other; these modifiers were used in order to incorporate differentiated or
      catalytic response to different polyphenols present in wine and aimed to the
      determination of its total polyphenol content value. The obtained voltammetric
      responses were pre-processed employing the Fast Fourier Transform (FFT); this was
      used to compress the relevant information whereas the obtained coefficients fed
      an Artificial Neural Network (ANN) model that accomplished the quantification of
      total polyphenol content. For comparison purposes, obtained polyphenol content
      was compared against the one assessed by two different reference methods: Folin
      Ciocalteu and UV polyphenol index (I(280)); good prediction ability was attained
      with correlation coefficients higher than 0.949 when comparing against reference
      methods. Qualitative discrimination of individual polyphenols found in wine was
      also assessed by means of Principal Component Analysis which allowed the
      discrimination of the individual polyphenols under study.

PMID- 22967593
TI  - Simple silver nanoparticle colorimetric sensing for copper by paper-based
      devices.
AB  - The first investigation of silver nanoparticle (AgNP) colorimetric sensing of
      Cu(2+) by paper-based analytical devices (PADs) is reported here. AgNP
      colorimetric sensing for the detection of Cu(2+) was first characterized by UV
      visible spectroscopy. The -SH groups on homocysteine (Hcy) and dithiothreitol
      (DTT) were used to modify the AgNP surface whereas the -COOH and -NH(2)
      functional groups have strong affinity to Cu(2+) relative to other ions in
      solution. The plasmon resonance absorption peak intensity at 404 nm decreased and
      a new red-shifted band at 502 nm occurred in the presence of Cu(2+). Paper
      devices coated with the modified AgNP solution changed from yellow to orange and
      green-brown color after the addition of Cu(2+) due to nanoparticle aggregation.
      The color intensity change as a function of Cu(2+) concentration gave a linear
      response in the range of 7.8-62.8 MUM (R(2)=0.992). The limit of naked-eye
      detection is 7.8 nM or 0.5 MUg L(-1). A color change observed by the naked eye
      with the addition of Cu(2+) can be clearly differentiated from the other metals
      (As(3+), Cd(2+), Co(2+), Hg(2+), Ni(2+), Pb(2+), Zn(2+), Mg(2+), Mn(2+), Ca(2+),
      Fe(3+), Na(+), and K(+)) at 15.7 MUM. The use of different flow directions in the
      PADs and MUPADs for Cu(2+) detection was also demonstrated. Levels of Cu(2+) in
      real water samples were measured using the paper devices to be 2.9+/-0.24 MUM
      (tap water) and 3.2+/-0.30 MUM (pond water), respectively, and were within error
      of the values measured using an atomic absorption spectrometer (2.8+/-0.08 MUM in
      tap water, and 3.4+/-0.04 MUM in pond water). Thus, this work shows the
      successful integration of paper devices and AgNP colorimetric sensing as a
      simple, rapid, easy-to-use, inexpensive and portable alternative point-of
      measurement monitoring.

PMID- 22967594
TI  - Prediction of Zamorano cheese quality by near-infrared spectroscopy assessing
      false non-compliance and false compliance at minimum permitted limits stated by
      designation of origin regulations.
AB  - Near-infrared transmittance (NIT) spectroscopy was used to predict the percentage
      in weight of the fat, dry matter, protein and fat/dry matter contents in Zamorano
      cheeses, protected with a Designation of Origin by the European Union. A total of
      42 cheeses submitted to official control were analysed by reference methods.
      Samples were scanned (850-1050 nm) and predictive equations were developed using
      Partial Least Squares regression with a cross-validation step. Eight
      pretreatments independent from the remaining calibration samples were first
      considered. The most adequate one was that performing the second derivative
      (using a Savitzky-Golay method with a nine-point window and a second-order
      polynomial) followed by the standard normal variate transformation. Percentages
      of the root mean square error in cross-validation, the coefficient of
      determination and the mean of the absolute value of relative errors found were,
      respectively, for fat (0.62; 96.16; 1.05), dry matter (0.76; 96.03; 0.83),
      protein (0.41; 97.82; 0.81) and the fat/dry matter ratio (0.61; 92.51; 0.66). At
      a 99% confidence level, the trueness of the NIT+PLS methods for fat, dry matter
      and protein was verified. The official regulation for Zamorano cheese demands
      minimum permitted limits on the percentages in weight for protein (25%), dry
      matter (55%) and the ratio of fat to dry matter (45%). The adaptation of both the
      decision limit and the detection capability to the case of a minimum permitted
      limit (CDalpha and CDbeta, respectively) when a Partial Least Squares calibration
      is used has been applied for the first time for a food product protected by a
      Designation of Origin. The values of CDalpha with a probability of false non
      compliance equal to 0.05 and of CDbeta when, in addition, the probability of
      false compliance was equal to or less than 0.05, both provided by the
      corresponding NIT+PLS-based method, were, respectively, for protein (24.78%;
      24.57%), dry matter (54.14%; 53.28%) and the fat/dry matter ratio (44.39%;
      43.78%).

PMID- 22967595
TI  - A rapid method for the differentiation of yeast cells grown under carbon and
      nitrogen-limited conditions by means of partial least squares discriminant
      analysis employing infrared micro-spectroscopic data of entire yeast cells.
AB  - This paper shows the ease of application and usefulness of mid-IR measurements
      for the investigation of orthogonal cell states on the example of the analysis of
      Pichia pastoris cells. A rapid method for the discrimination of entire yeast
      cells grown under carbon and nitrogen-limited conditions based on the direct
      acquisition of mid-IR spectra and partial least squares discriminant analysis
      (PLS-DA) is described. The obtained PLS-DA model was extensively validated
      employing two different validation strategies: (i) statistical validation
      employing a method based on permutation testing and (ii) external validation
      splitting the available data into two independent sub-sets. The Variable
      Importance in Projection scores of the PLS-DA model provided deeper insight into
      the differences between the two investigated states. Hence, we demonstrate the
      feasibility of a method which uses IR spectra from intact cells that may be
      employed in a second step as an in-line tool in process development and process
      control along Quality by Design principles.

PMID- 22967596
TI  - Thiolated DAB dendrimer/ZnSe nanoparticles for C-reactive protein recognition in
      human serum.
AB  - A nanocomposite obtained by a thiol DAB-dendrimer (generation 5), coated with
      fluorescent ZnSe quantum dots, was successfully synthesized for the selective
      recognition of C-reactive protein. The procedure presented was carried out by a
      novel, cheap and non-toxic bottom up synthesis. The nanocomposite showed an
      excitation at 180 nm, with two emission bands at 411 and 465 nm, with a full
      width at half-maximum of 336 nm. The Stokes shift was influenced by the presence
      of coating molecules and the intensity was dependent on pH due to the presence of
      a charge transfer process. The transmission electron microscopy images
      demonstrated that the spherical nanoparticles obtained displayed a regular shape
      of 30 nm size. The fluorescence intensity was markedly quenched by the presence
      of C-reactive protein, with a dynamic Stern-Volmer constant of 0.036 M(-1). The
      quenching profile shows that about 51% of the ZnSe QDs are located in the
      external layer of the thiol dendrimer accessible to the quencher. The precision
      of the method obtained as relative standard deviation was 3.76% (4 mg L(-1),
      n=3). This water soluble fluorescent nanocomposite showed a set of favorable
      properties to be used as a sensor for the C-reactive protein in serum samples, at
      concentrations of risk levels.

PMID- 22967597
TI  - Non-covalent functionalisation of monolithic silica for the development of carbon
      nanotube HPLC stationary phases.
AB  - In this paper, an effective and simple method was used for the immobilization of
      single wall carbon nanotubes (SWCNTs) on a monolithic HPLC material containing 2
      MUm macropore sizes and 13 nm mesopore sizes. The chromatographic support was
      coated with ultra short SWCNTs in a noncovalent way to preserve the sp(2)
      nanotube structure and thus their physico-chemical properties. It was
      demonstrated that the amino-surface of the monolith stabilized with 1-methyl-2
      pyrrolidinone efficiently and stably adsorbed SWCNTs onto the chromatographic
      support. It was shown that this novel stationary phase was very useful for the
      HPLC isocratic mode separation of a series of small aromatic compounds in a very
      short analysis time. The comparison with a classical equivalent C18 monolithic
      column showed that the SWCNT column presented the best efficiency in similar
      chromatographic conditions.

PMID- 22967598
TI  - Separation and analysis of lanthanides by isotachophoresis coupled with
      inductively coupled plasma mass spectrometry.
AB  - This study is a large project initiated by the French Nuclear Agency, and
      concerns the development of a new electrolyte system for the separation of
      lanthanides by isotachophoresis. This new system is based on a leading
      electrolyte that incorporates 2-hydroxy-2-methylbutyric acid as complexing agent.
      The optimization of separation conditions (complexing agent concentration, pH,
      capillary dimensions, injection conditions, and current intensity) performed by
      experiments on a commercial capillary instrument with contactless conductivity
      detection, which allows to improve the separation of 13 lanthanides (La to Lu,
      except Pm and Ho). We have also directly coupled the isotachophoresis to an
      inductively coupled plasma mass spectrometer to visualize the mono-elementary
      elution bands and demonstrate the potentiality of the method for isotope ratio
      measurements. The application to a simulated solution representative of a
      fraction of fission products present in a MOX spent fuel is presented in this
      paper to demonstrate the possible application in future on nuclear fuel samples.

PMID- 22967599
TI  - Microwave assisted EDTA extraction-determination of pseudo total contents of
      distinct trace elements in solid environmental matrices.
AB  - Quantitative determination of metals in environmental matrices became important
      in the past few decades because of increasing pollutant concentrations in aquatic
      and terrestrial ecosystems. The extraction phase in the process of determining
      metals is crucial but very time-consuming. Consequently, new extraction
      techniques for extractable metals have been developed which probably will
      substitute conventional procedures in the future. The aim of this study was to
      improve a closed vessel microwave assisted extraction (MAE) by using EDTA as an
      exclusive extraction agent (MAE-EDTA) for the determination of pseudo total metal
      contents in solid environmental samples. For this purpose, a large set of soil
      and compost samples were analyzed. MAE-EDTA was compared with both closed vessel
      microwave assisted aqua regia extraction (MAE-AR) and a conventional aqua regia
      extraction (AR) method for the determination of pseudo total Cd, Cu, Mn, and Pb
      contents of soil and compost samples. Certified reference materials were used for
      comparison of recovery rates from different extraction protocols. Metal
      concentrations in soil and compost extracts were determined by ICP-OES. MAE-AR
      which was considered as a reference MAE method for further steps of the study,
      showed the same extraction yields in the determination of pseudo total metal
      contents of the investigated elements (As, Ba, Be, Cd, Co, Cr, Cu, Mn, Ni, Pb, V,
      Zn) in soil and compost samples as the conventional AR. MAE-EDTA gave similar
      values as the reference methods in the determination of Cd, Cu, and Pb amounts in
      soil samples and Cd, Mn, and Pb amounts in compost samples. The recovery rates
      ranged between 89.0-117.1% for soil samples and 93.5-104.0% for compost samples.
      MAE-EDTA provides fast processing of the samples that is less than one hour,
      including time for cooling of the samples. Apart from significantly less
      processing time, minimal consumption of sample and reagent chemicals is a
      strategic characteristic of MAE-EDTA procedure which has advantages including
      accuracy and reduction of contamination. The drawback of MAE-EDTA was that the
      optimized conditions for the metals Cd, Cu, Mn and Pb may not be generally
      applicable for the other metals. Therefore, the analytical parameters available
      in MAE-EDTA should be further investigated for the metals of interest.

PMID- 22967600
TI  - Simultaneous measurement of protein-bound 3-chlorotyrosine and homocitrulline by
      LC-MS/MS after hydrolysis assisted by microwave: application to the study of
      myeloperoxidase activity during hemodialysis.
AB  - A high degree of uremia is common in patients with end-stage renal disease and
      has been linked to the development of chronic inflammation and cardiovascular
      diseases. In conditions where transplantation is not possible, uremia can be
      reduced by hemodialysis although the repeated interventions have been implicated
      in loss of renal function, partially as a result of chronic inflammation and/or
      oxidative stress processes. In this context, it has been suggested that
      myeloperoxidase (MPO) can contribute to the oxidative stress during hemodialysis
      and to the cardiovascular risk. Protein damages due to MPO activity have never
      been assessed during hemodialysis although two of its reaction products, 3
      chlorotyrosine and homocitrulline, are of interest. Indeed, the first one is a
      specific product of MPO activity and the formation of the second one could be
      catalyzed by MPO. In order to analyze these products in plasma proteins, a total
      hydrolysis method followed by liquid chromatography mass spectrometry analysis
      was developed. Different conditions of hydrolysis were tested and the optimized
      procedure was assessed for complete hydrolysis and artifactual chlorination.
      Finally, the method was used for analyzing 3-chlorotyrosine and homocitrulline in
      plasma proteins during a hemodialysis session in fifteen patients and data were
      related to measurements of MPO concentration and activity. Both increases in MPO
      activity and protein-bound 3-chlorotyrosine were observed, highlighting the
      involvement of MPO in oxidative stress during hemodialysis and further
      demonstrating the link between hemodialysis and cardiovascular diseases.

PMID- 22967601
TI  - A reaction based turn-on type fluorogenic and chromogenic probe for the detection
      of trace amount of nitrite in water.
AB  - A turn-on fluorescent probe for the detection of nitrite ion in water is
      developed based on diazotization reaction of the amino group of the probe in an
      acidic solution (pH 1). The probe responds selectively to nitrite ion over
      various other anions with a turn-on type fluorogenic change from colorless to
      orange by the formation of rhodamine B via an analyte triggered fragmentation
      process. The fluorescence titration is complete within 1h with 1 equivalent of
      nitrite ion. The probe is highly efficient, cost-effective and shows a detection
      limit of 4.6 ppb.

PMID- 22967602
TI  - Multiclass analysis of antibacterial residues in milk using RP-liquid
      chromatography with photodiode array and fluorescence detection and tandem mass
      spectrometer confirmation.
AB  - A simplified procedure for simultaneous quantification of ceftiofur (CEF),
      fluoroquinolone (FQ) and sulfonamide (SA) antibacterials in bovine milk was
      developed. The reverse-phase liquid chromatography (RP-LC) multiclass method for
      analysis of eleven distinct compounds, from three antibacterial classes, was
      validated in line with Commission Decision 2002/657/EC. Confirmation of the
      analytes identities was performed by electrospray mass spectrometry detection.
      The analytes were extracted from milk matrix by liquid-liquid extraction with
      acidified ultrapure water and directly analyzed in the chromatograph. The SA
      compounds were pre-column derivatized with fluorescamine for fluorescence
      detection. The method provided good results regarding the analytical parameters
      of linearity, selectivity, sensitivity, precision, recovery, decision limit
      (CCalpha), detection capability (CCbeta), limit of detection (LOD), limit of
      quantification (LOQ), stability and robustness. Analytes were extracted by liquid
      liquid extraction in the fortified matrix and the compounds identity was
      confirmed by their precursor ion and fragments through tandem mass spectrometry
      analysis. Additionally, milk samples from two state capitals in the South Region
      of Brazil were analyzed by both the quantitative and confirmatory methods. The
      validation process showed correlation coefficients (r(2)) greater than 0.98 for
      all the analytes, with recovery rates up to 98% for all the studied drugs. LOD
      and LOQ limits ranged from 8.0 to 20.0 ng mL(-1) and 10.0 to 32.0 ng mL(-1),
      demonstrating good specificity of the method. The intra-day and inter-day
      precisions for all the analytes were below or equal to 7.40 and 10.13,
      respectively. The studied antibacterials were not detected in milk samples. The
      developed method represents an efficient alternative for multi-residue analysis
      in milk, being suitable and especially viable for monitoring in developing
      countries.

PMID- 22967603
TI  - Detection of DNA damage by using hairpin molecular beacon probes and graphene
      oxide.
AB  - A hairpin molecular beacon tagged with carboxyfluorescein in combination with
      graphene oxide as a quencher reagent was used to detect the DNA damage by
      chemical reagents. The fluorescence of molecular beacon was quenched sharply by
      graphene oxide; while in the presence of its complementary DNA the quenching
      efficiency decreased because their hybridization prevented the strong
      adsorbability of molecular beacon on graphene oxide. If the complementary DNA was
      damaged by a chemical reagent and could not form intact duplex structure with
      molecular beacon, more molecular beacon would adsorb on graphene oxide increasing
      the quenching efficiency. Thus, damaged DNA could be detected based on different
      quenching efficiencies afforded by damaged and intact complementary DNA. The
      damage effects of chlorpyrifos-methyl and three metabolites of styrene such as
      mandelieaeids, phenylglyoxylieaeids and epoxystyrene on DNA were studied as
      models. The method for detection of DNA damage was reliable, rapid and simple
      compared to the biological methods.

PMID- 22967604
TI  - Speciation analysis of mercury in sediments using vortex-assisted liquid-liquid
      microextraction coupled to high-performance liquid chromatography-cold vapor
      atomic fluorescence spectrometry.
AB  - A simple and fast solvent microextraction method termed vortex-assisted liquid
      liquid microextraction (VALLME) coupled with high-performance liquid
      chromatography-vapor generation atomic fluorescence spectrometry (HPLC-CVAFS) has
      been developed for the trace analysis of methylmercury (MeHg(+)), ethylmercury
      (EtHg(+)) and inorganic mercury (Hg(2+)) in sediment samples. Carbon
      tetrachloride was used as collecting solvent for the extraction of mercury
      species from sediment by a vortex-assisted extraction. In VALLME, 100 MUL 1%
      (m/v) l-Cysteine were used as extraction solvent and were injected into 4 mL
      carbon tetrachloride. The extraction solvent dispersed into carbon tetrachloride
      under vigorously shaking by a vortex agitator. The fine droplets could extract
      mercury species within few minutes because of the shorter diffusion distance and
      larger specific surface area. After centrifugation, the floating extractant phase
      restored its initial single microdrop shape and was used for HPLC-CVAFS analysis.
      The parameters affecting the extraction efficiency of the proposed VALLME such as
      extraction solvent, vortex time, volumes of extraction solvent and salt addition
      etc. were investigated. Under the optimum conditions, linearity was found in the
      concentration range from 0.1 to 25 ng g(-1) for MeHg(+), 0.2 to 65 ng g(-1) for
      EtHg(+), and 0.1 to 30 ng g(-1) for Hg(2+). Coefficients of determination (R(2))
      ranged from 0.9938 to 0.9972. The limits of detection (LODs, signal-to-noise
      ratio (S/N)=3) were 0.028 ng g(-1) for MeHg(+), 0.057 ng g(-1) for EtHg(+), and
      0.029 ng g(-1) for Hg(2+). Reproducibility and recoveries were assessed by
      testing a series of 6 sediment samples, which were spiked with different
      concentration levels. Finally, the proposed method was successfully applied in
      analyses of real nature sediment samples. In this work, VALLME was applied to the
      extraction of mercury species in sediment samples for the first time. Using l-Cys
      as extraction solvent, the extraction process is sensitive and environmentally
      friendly and could be achieved within 3 min.

PMID- 22967605
TI  - Simple and sensitive aptasensor based on quantum dot-coated silica nanospheres
      and the gold screen-printed electrode.
AB  - A novel electrochemical aptasensor involving quantum dots-coated silica
      nanospheres (QDs/Si) and the screen-printed gold electrodes (SPGE) was developed
      for the detection of thrombin. The screen-printed electrodes with several
      advantages, including low cost, versatility, miniaturization, and mechanical
      regeneration after each measurement cycle, were employed. On the other hand, the
      gold nanoparticles (AuNPs) were electrodeposited on the surface of SPGE to obtain
      AuNPs/SPGE. And this sandwich format (Apt/thrombin/Apt-QDs/Si) was fixed on the
      AuNPs/SPGE to fabricate the electrochemical aptasensor. The bound CdTe QDs were
      dissolved in an acid-dissolution step and were detected by electrochemical
      stripping analysis. The proposed aptasensor has excellent performance such as
      high sensitivity, good selectivity and analytical application in real samples.
      The combination of nanoparticles with the screen-printed electrode is favorable
      for amplifying electrochemical signals, and useful for large-scale fabrication of
      the electrochemical aptasensors, which would lay a potential foundation for the
      development of the electrochemical aptasensor.

PMID- 22967606
TI  - Enhanced chemiluminescence of the luminol-hydrogen peroxide system by colloidal
      cupric oxide nanoparticles as peroxidase mimic.
AB  - As a peroxidase mimic, cupric oxide nanoparticles were found to enhance the
      chemiluminescence (CL) of luminol-H(2)O(2) system up to 400 folds. The CL spectra
      and radical scavengers were conducted to investigate the possible CL enhancement
      mechanism. It was suggested that the enhanced CL could be attributed to the
      peroxidase-like activity of CuO nanoparticles, which effectively catalyzed the
      decomposition of hydrogen peroxide into hydroxyl radicals. The effects of the
      reactant concentrations and some organic compounds were also investigated. The
      proposed method could be used as a sensitive detection tool for hydrogen peroxide
      and glucose.

PMID- 22967607
TI  - A rapid UPLC-MS/MS method for simultaneous determination of flunitrazepam, 7
      aminoflunitrazepam, methadone and EDDP in human, rat and rabbit plasma.
AB  - A simple, high-throughput, sensitive LC-ESI-MS/MS method is presented for the
      simultaneous determination of methadone (MET), flunitrazepam (FNZ) and their
      major metabolites, EDDP (2-ethilidene-1,5-dimethyl-3,3-diphenylpyrrolidone) and 7
      aminoflunitrazepam (7-AFNZ), respectively, in human, rat and rabbit plasma. The
      isolation of the selected compounds involved a liquid-liquid extraction with
      ethyl acetate at a basic pH. Good chromatographic separation was achieved on a
      HSS T3 column (1.8 MUm particle size), with a 3 min gradient elution using a
      mixture of acetonitrile with 0.1% formic acid (solvent A) and 5mM ammonium
      acetate (solvent B) as the mobile phase. The tandem mass spectrometric detection
      was performed in multiple reaction monitoring (MRM) mode with ionization of the
      analytes in positive mode. The assay was fully validated according to current
      acceptance criteria for bioanalytical methods validation. It was proved to be
      linear in the range of 0.5-250 ng/mL, with adequate accuracy and precision over
      this range. Based on accuracy and CV% values the LOQ and ULOQ values were set at
      0.509 ng/mL and 2036 ng/mL for MET, 0.520 ng/mL and 2080 ng/mL for EDDP, 0.524
      ng/mL and 2096 ng/mL for FNZ and 0.528 ng/mL and 2114 ng/mL for 7-AFNZ,
      respectively. The method was tested for potential matrix effects, without
      observing significant ion suppression. The investigated compounds stability was
      examined in plasma at room temperature and after three freeze-thaw cycles and in
      the final extract when maintained at 4  degrees C in the autosampler. Potential
      stability issues were observed only for FNZ at room temperature. The method was
      successfully applied to quantify the selected compounds in human, rat and rabbit
      plasma samples, after exposure to FNZ or simultaneous exposure to FNZ and MET.

PMID- 22967608
TI  - An infrared spectroscopic tool for process monitoring: sugar contents during the
      production of a depilatory formulation.
AB  - A fast, reliable and economical methodology has been developed to control the
      production process of sugar-based depilatories. The method is based on the use of
      attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy
      in combination with multivariate data analysis. A very simple sample preparation
      process involving the dissolution of samples in water was applied. Employing a
      multivariate calibration model established from data of 15 well characterized
      samples, prediction errors equal or below 3.04 mg mL(-1) for the quantitative
      determination of fructose, glucose, sucrose, maltose and maltotriose were
      obtained. Results found in this preliminary study indicate a great potential for
      the development of at-line ATR-FTIR-PLS methods based on a careful selection of
      variables from IR spectra, delivering fast and reliable results. As a reference
      method, a liquid chromatography (LC)-IR method was adapted for sample
      characterization.

PMID- 22967609
TI  - Developing improved immunoassays for paralytic shellfish toxins: the need for
      multiple, superior antibodies.
AB  - Paralytic shellfish toxins (PSTs) are a risk to humans upon consumption of
      contaminated seafood. The PST family is comprised of more than twenty congeners,
      with each form having a different potency. In order to adequately protect
      consumers yet reduce unnecessary closures of non-contaminated harvesting areas, a
      rapid method that allows for analysis of sample toxicity is needed. While a
      number of PST immunoassays exist, the outstanding challenge is linking
      quantitative response to sample toxicity, as no single antibody reacts to the PST
      congeners in a manner that correlates with potency. A novel approach, then, is to
      combine multiple antibodies of varying reactivity to create a screening assay.
      This research details our investigation of three currently available antibodies
      for their reactivity profiles determined using a surface plasmon resonance
      biosensor assay. While our study shows challenges with detection of the R1
      hydroxylated PSTs, results indicate that using multiple antibodies may provide
      more confidence in determining overall toxicity and the toxin profile. A
      multiplexed approach would not only improve biosensor assays but could also be
      applied to lateral flow immuno-chromatographic platforms, and such a theoretical
      device incorporating the three antibodies is presented. These improved assays
      could reduce the number of animal bioassays and confirmatory analyses (e.g.,
      LC/MS), thereby improving food safety and economic use of shellfish resources.

PMID- 22967610
TI  - Ultra trace determination of bromate in mineral water and table salt by liquid
      chromatography-tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed
      in order to determine the bromate in mineral water and table salt. The following
      optimum conditions for the LC-MS/MS detection were established: derivatization
      reagent (300 mg/L of 2,6-dimethylaniline), acidity (0.2M HCl), reaction
      temperature (30  degrees C) and heating time (20 min). The formed derivative was
      directly injected in the LC system without extraction or purification procedures.
      In the established conditions, the method was used to detect bromate in mineral
      water and table salt. The limit of detection and limit of quantification of
      bromate in mineral water were 0.02 MUg/L and 0.07 MUg/L, respectively, and those
      of table salt were 0.07 MUg/kg and 0.23 MUg/kg, respectively. The 17 common ions
      did not interfere even when present in 1,000-fold excess over the bromated ion of
      10.0 MUg/L. The accuracy was in a range of 92-104% and the assay precision was
      less than 9% in the table salt. The method was successfully applied to determine
      bromate in mineral water and table salt.

PMID- 22967611
TI  - Monitoring the subcellular localization of doxorubicin in CHO-K1 using MEKC-LIF:
      liposomal carrier for enhanced drug delivery.
AB  - Doxorubicin (DOX) is an extensively used anthracycline that has proven to be
      effective against a variety of human malignant tumors, such as ovarian or breast
      cancer. While DOX was administered into cultured cancer cell targets (such as CHO
      K1) in either free drug form or in drug carrier-associated form (i.e., DOX
      encapsulated in the drug delivery carrier), various action of mechanisms for DOX
      were initiated, among which, it has been long believed that DOX enters the
      nucleus, interacts with DNA in numerous ways, and finally halts cell
      proliferation. Aside from its therapeutic effect, regrettably DOX treatment may
      be accompanied by the occurrence of cardiac and liver toxicity and drug
      resistance that are attributed from cellular processes involving the parent drug
      or its metabolites. Liposomal formulation of DOX, known to be capable of
      attenuating direct uptake of reticuloendothelial system (RES) and prolonging the
      circulation time in blood, demonstrated reduced toxic side-effects. We herein
      report the development of a modified MEKC-LIF (Micellar electrokinetic
      chromatography-Laser-induced fluorescence) method suitable for analyzing DOX in
      biological samples. The MEKC migration buffer, consisting of 10 mM borate, 100 mM
      sodium dodecyl sulfate (SDS) (pH 9.3), was found to provide an efficient and
      stable electrophoretic separation and analysis for DOX. Responses were linear in
      the range of 11.3-725 ng/mL; the limit of quantitation (LOQ) was found to be 43.1
      ng/mL (S/N=10) (equivalent to 74.3 nM) and limit of detection (LOD) was
      calculated as 6.36 ng/mL (S/N=3) (equivalent to 11.0 nM). This approach was
      subsequently employed to compare the intracellular accumulation in three
      subcellular fractions of DOX-treated CHO-K1 cells. These fractions form a pellet
      at <1400 g, 1400-14000 g, and >14000 g and are enriched in nuclei, organelles
      (mitochondria and lysosomes), and cytosole components, respectively, resulting
      from treatment of CHO-K1 cells with 25 MUM (equivalent to 14.5 MUg/mL) of two DOX
      formats (in free drug form or liposomal form synthesized in current study) for
      different periods of time. Our results indicated that the most abundant DOX was
      found in the nuclear-enriched fraction of cells treated for 12 h and 6 h with
      free and liposomal DOX, respectively, providing direct evidence to confirm the
      enhanced efficiency of liposomal carriers in delivering DOX into the nucleus. The
      observations presented herein suggest that subcellular fractionation followed by
      liquid-liquid extraction and MEKC-LIF could be a powerful diagnostic tool for
      monitoring intracellular DOX distribution, which is highly relevant to
      cytotoxicity studies of anthracycline-type anticancer drugs.

PMID- 22967612
TI  - Novel spectroscopic sensor for the hydroxyl radical scavenging activity
      measurement of biological samples.
AB  - A novel spectroscopic sensor was developed and validated for hydroxyl radical
      scavenging (HRS) activity estimation using terephthalate (TP) as probe. This
      sensor was designed by electrostatic immobilization of the chromogenic oxidizing
      agent of the CUPric Reducing Antioxidant Capacity (CUPRAC) method, Cu(II)
      Neocuproine (Cu(II)-Nc) complex, on a Nafion cation-exchange membrane, and the
      spectrophotometric assay developed in aqueous-alcoholic solutions was integrated
      to the CUPRAC sensor. Hydroxyl radicals ((*)OH) generated from an equivalent
      mixture of Fe(II)+EDTA with hydrogen peroxide attacked both the probe and the
      (*)OH scavengers in 37  degrees C-incubated solutions for 1/2h. The HRS activity
      was measured using the decrease in CUPRAC absorbance at 450 nm - arising from the
      reduction of Cu(II)-Nc reagent to the Cu(I)-neocuproine chelate - of the
      hydroxylated probe (TP) undergoing radical attack in the presence of (*)OH
      scavengers. The HRS activity was evaluated as the second-order rate constants of
      biologically active compounds for (*)OH scavenging and also as the percentage
      scavenging of a measured compound or sample relative to a reference compound.
      Using this reaction, a kinetic approach was adopted to assess the HRS activity of
      amino acids, plasma- and thiol-antioxidants. This assay, applicable to small
      molecule antioxidants and tissue homogenates, proved to be efficient for serine
      and albumin for which the widely used TBARS (thiobarbituric acid-reactive
      substances) test is nonresponsive. Under optimal conditions, about half of the
      probe (TP) was converted into 2-hydroxyterephthalate (hTP), and this
      monohydroxylated derivative, being the only product of hydroxylation, was a more
      specific marker of (*)OH than the non-specific malondialdehyde end-product of the
      TBARS test. The sensor gave a linear response to scavenger concentration in the
      competition kinetic equation.

PMID- 22967613
TI  - Enzyme biosensor for androsterone based on 3alpha-hydroxysteroid dehydrogenase
      immobilized onto a carbon nanotubes/ionic liquid/NAD+ composite electrode.
AB  - A 3alpha-hydrosteroid biosensor for androsterone determination has been prepared
      by immobilizing the enzyme 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) in a
      composite electrode platform constituted of a mixture of multi-walled carbon
      nanotubes (MWCNTs), octylpyridinium hexafluorophosphate (OPPF(6)) ionic liquid
      and NAD(+) cofactor. This configuration allowed the fast, sensitive and stable
      electrochemical detection of the NADH generated in the enzyme reaction. All the
      experimental variables involved in the preparation and performance of the enzyme
      biosensor were optimized. Amperometry in stirred solutions at +400 mV provided a
      linear calibration plot for androsterone in the 0.5-10 MUM concentration range
      with a slope value more than 200-times higher than that previously reported. The
      detection limit achieved was 0.15 MUM and a low value of the apparent Michaelis
      Menten constant (K(app)(M)), 36.0 MUM, similar to that reported for the enzyme in
      solution, was calculated. The 3alpha-HSD/MWCNTs/OPPF(6)/NAD(+) biosensor provided
      good results in the determination of androsterone in spiked human serum samples.

PMID- 22967614
TI  - Determination of copper in liquid and solid insulation for large electrical
      equipment by ICP-OES. Application to copper contamination assessment in power
      transformers.
AB  - Copper is one of the main constituents of the components in power transformers
      and its presence both in liquid (mineral oil) and in solid (Kraft paper)
      insulators can lead to enhanced dielectric losses and to the subsequent
      deterioration of their insulating properties. Recently the latter have been
      correlated to plant failures which in turn may have severe impact on the
      environment. This paper describes the direct analysis of copper in insulating
      mineral oil by ICP-OES and how it was first optimized compared to the official
      American Society for Testing and Materials (ASTM) D7151 method. Detection and
      quantification limits of 8.8 MUg kg(-1) and 29.3 MUg kg(-1) were obtained.
      Secondly, copper determination was improved by coupling a microwave assisted
      dissolution procedure of the mineral oil which avoided the problems, in the real
      samples, due to the presence of solid species of copper which cannot be nebulized
      following traditional methods described in literature. Sixteen mineral insulating
      oils sampled from transformers in service were analyzed before and after
      dissolution. In order to evaluate copper speciation, size fractionation was
      performed by filtration on PTFE filters (0.45, 1 and 5 MUm). This test was
      performed on all the oil samples. Finally, because of the key role of the solid
      insulator in failed transformers, the Authors applied the developed method to
      study the copper deposition tendency onto the insulating Kraft paper tapes
      exerted by two unused oils (a corrosive and a non-corrosive one) under defined
      ageing conditions.

PMID- 22967615
TI  - Analysis of mycotoxins in barley using ultra high liquid chromatography high
      resolution mass spectrometry: comparison of efficiency and efficacy of different
      extraction procedures.
AB  - The effectiveness of four extraction methods (modified QuEChERS, matrix solid
      phase dispersion (MSPD), solid-liquid extraction (SLE) and solid-phase extraction
      (SPE) clean-up) were evaluated for simultaneous determination of 32 mycotoxins
      produced by the genus Fusarium, Claviceps, Aspergillus, Penicillium and
      Alternaria in barley by ultra high pressure liquid chromatography coupled to
      ultra-high resolution mass spectrometry (UHPLC-Orbitrap((r)) MS). The efficiency
      and efficacy of extraction methods were evaluated and compared in number of
      extracted mycotoxins and obtained recoveries. From the one point of view,
      QuEChERS procedure was fast and easy, as well as it was able to successfully
      extract all selected mycotoxins. On the other hand, SLE method, MSPD and SPE
      clean-up method did not extract adequately all selected mycotoxins and recoveries
      were not suitable enough. Thereby, method employing QuEChERS extraction connected
      with UHPLC-Orbitrap((r)) MS was developed to quantify 32 mycotoxins in barley
      within this study. Analytical method was validated and recoveries ranged from 72%
      to 101% for selected mycotoxins with only one exception nivalenol (NIV) and
      deoxynivalenol-3-glucoside (D3G), which were lower than 67%. Relative standard
      deviations (RSD) were lower than 17.4% for all target mycotoxins. The lowest
      calibration levels (LCLs) ranged from 1 to 100 MUg/kg. Validated method was
      finally used for monitoring mycotoxins in a total of 15 Czech barley samples,
      when only Fusarium toxins representatives were detected in 53% of samples and the
      mycotoxins with the highest incidence were enniatins.

PMID- 22967616
TI  - Improvement of uptake rate equations depending on meteorological conditions for
      25 volatile organic compounds.
AB  - Stainless steel passive (diffusive) sampling tubes manufactured by Gradko
      International Ltd. (UK) were filled with Chromosorb 106 (Supelco) and evaluated
      to determine the uptake rates of 31 VOCs over six months under different
      meteorological conditions in a suburban area of Ankara, Turkey. The URs have been
      calculated, and dependence on such meteorological parameters as temperature,
      relative humidity and wind speed has been established for the 31 VOCs. The URs of
      the 31 VOCs measured in this study showed a statistically significant decreasing
      trend with rising temperature; and weaker, but again statistically significant,
      increasing trends with increasing relative humidity and wind speed. This study
      has demonstrated that the URs of VOCs are affected by meteorological parameters,
      and this dependence should be taken into account when attempting to generate
      reliable data through passive sampling. A multiple linear regression equation in
      which temperature, relative humidity and wind speed were used as independent
      variables was generated for 25 of the 31 tested VOCs.

PMID- 22967617
TI  - Sensitive determination of chromium (VI) in paint samples using a membrane optode
      coupled to a multisyringe flow injection system.
AB  - In this work, the potential of a membrane optode coupled to a multisyringe flow
      injection system (MSFIA) was assessed for determining the Cr(VI) concentration in
      paint samples. The detection is based on the color obtained from the reaction of
      Cr(VI) with 1,5-diphenylcarbazide in the presence of sulfuric acid (H(2)SO(4)).
      The redox product was immobilized on a poly(styrene-divinylbenzene) (SDB-XC)
      membrane optode. The analyte in the sample was then directly quantified at the
      surface of the disk by measuring the intensity of reflected incident light using
      a bifurcated optical fiber at 540 nm. Experimental parameters (concentration of
      reagents, sample volume, flow rate of sample solutions, eluent concentration, and
      effect of diverse ions) were studied in detail. The overall time required for the
      complete procedure was 4 min and only required 0.2 mL of the sample volume. The
      dynamic working response of Cr(VI) was found within the concentration range of
      2.4-1000 MUg L(-1) with a limit of detection (LOD) of 0.7 MUg L(-1), while the
      relative standard deviation (RSD) for 400 MUg L(-1) Cr(VI) was lower than 2%
      (n=6). This developed method was used to determine Cr(VI) concentrations in the
      paint samples, for which an alkaline extraction procedure was proposed. The
      extraction procedure was based on the use of a 7.5% Na(2)CO(3)/5% NaOH solution
      at 90  degrees C for 30 min. Under optimal conditions, the recoveries ranged from
      99% to 101%. The complete method was validated using a certified reference
      material (ERA-QC540, soil sample) and by comparing the results with those
      obtained using atomic absorption spectrometry (AAS).

PMID- 22967618
TI  - Thick-film voltammetric pH-sensors with internal indicator and reference species.
AB  - The following paper describes the development of a screen-printed voltammetric pH
      sensor based on graphite electrodes incorporating both internal indicator (i.e.,
      phenanthraquinone) and reference species (i.e., dimethylferrocene). The key
      advantages of this type of system stem from its simplicity, low cost and ease of
      fabrication. More importantly, as opposed to conventional voltammetric systems
      where the height of the voltammetric peaks is taken into account to quantify the
      amount of a species of interest, here, the difference between the peak potential
      of the indicator species and the peak potential of the reference species is used.
      Thus, this measurement principle makes the electrochemical system presented here
      less dependent on the potential of the reference electrode (RE), as is often the
      case in other electrochemical systems. The developed system displays very
      promising performances, with a reproducible Super Nernstian response to pH
      changes and a lifetime of at least nine days.

PMID- 22967619
TI  - A rapid online estimation method for radiostrontium in soil samples using crown
      ether and supercritical fluid extraction.
AB  - Crown ethers dissolved in suitable medium are well known to promote the
      extraction of alkali (M(+)) and alkaline-earth (M(2+)) cations from aqueous to
      organic phases. Di-tert-butyl-cyclohexano18crown6 (DTBDCH18C6) has been
      identified as an effective and selective extractant for Sr(II) from nitric acid
      medium. An attempt was made to evaluate the feasibility of (85,89)Sr recovery
      from synthetic soil samples (0.5 g; particle size: <100 MUm) by SFE route
      (pressure: 200 kg/cm(2); T: 40  degrees C) employing DTBDCH18C6 dissolved in
      methanol/nitric acid medium as phase modifier. The effect of various experimental
      parameters such as (i) dynamic/static mode of extraction, (ii) time of
      equilibration (15-150 min during static mode of extraction using 3 mL of
      modifier), (iii) nitric acid concentration (1-6M), (iv) picrate as counter-anion,
      and (v) crown ether concentration in the modifier phase (2*10(-4)-2*10(-3) M) on
      Sr(II) extraction was studied. Based on these studies, 2*10(-4) M DTBDCH18C6
      dissolved in methanol/4M HNO(3) was chosen as modifier and 30 min as
      equilibration time for batch mode employing 3 mL modifier solution in the static
      mode. Three successive batches employing 3 mL modifier solution (after each
      extraction stage) showed near quantitative recovery (>95%) of (85,89)Sr from soil
      samples. Dynamic mode extraction using 2*10(-4) M DTBDCH18C6 dissolved in
      methanol/4M HNO(3) as modifier suggested that near quantitative recovery (>95%)
      of (85,89)Sr could be achieved within 1h. By contrast, ~10% (137)Cs extraction
      was observed from soil samples under identical experimental conditions. These
      studies demonstrate the potential of the SFE technique for the analysis of (90)Sr
      in different environmental samples.

PMID- 22967620
TI  - Determination of gold in geological materials by carbon slurry sampling graphite
      furnace atomic absorption spectrometry.
AB  - A simple and cost effective preconcentration method on modified activated carbons
      is described for the determination of traces of gold (Au) in geological samples
      by carbon slurry sampling graphite furnace atomic absorption spectrometry
      (GFAAS). The basic parameters affecting the adsorption capacity of Au(III) ions
      on modified activated carbons were studied in detail and the effect of activated
      carbons modification has been determined by studying the initial runs of
      adsorption isotherms. The influence of chlorides and nitrates on adsorption
      ability of Au(III) ions onto the modified activated carbons for diluted aqueous
      solution was also studied in detail in respect to the determination of gold in
      solid materials after digestion steps in the analytical procedure, which usually
      involves the application of aqua regia. SEM-EDX and XPS studies confirmed that
      the surface reduction of Au(III) ions to Au(0) is the main gold adsorption
      mechanism on the activated carbon. Determination of gold after its
      preconcentration on the modified activated carbon was validated by applying
      certified reference materials. The experimental results are in good agreement
      with the certified values. The proposed method has been successfully applied for
      the determination of Au in real samples using aqueous standards.

PMID- 22967621
TI  - Preconcentration and speciation of trace amounts of chromium in saline samples
      using temperature-controlled microextraction based on ionic liquid as extraction
      solvent and determination by electrothermal atomic absorption spectrometry.
AB  - A sensitive and selective method for the preconcentration and speciation of sub
      ng L(-1) levels of chromium species in aqueous solutions with high salt contents
      is described. The developed method is based on temperature-controlled
      microextraction of chromium species using the 1-hexyl-3-methylimidazolium
      hexafluorophosphate ([HMIM][PF(6)]) ionic liquid as an extractant followed by
      electrothermal atomic absorption spectrometry (ETAAS) determination. The
      extraction of chromium species from aqueous solution into the fine droplets of
      [HMIM][PF(6)] was performed with ammonium pyrrolidine dithiocarbamate (APDC) as
      the chelating agent. Some predominant factors affecting the preconcentration and
      speciation of both Cr(III) and Cr(VI) species were evaluated and optimized. Under
      the optimum conditions, the calibration graphs were linear over the concentration
      ranges from 50 to 200 ng L(-1) for Cr(III) and from 25 to 150 ng L(-1) for
      Cr(VI). The limits of detection (LOD) of the developed method were 5.40 ng L(-1)
      and 2.45 ng L(-1) for Cr(III) and Cr(VI) ions, respectively. The enrichment
      factor for chromium species was found to be 42. The relative standard deviations
      for six replicate determinations of 100 ng L(-1) of either Cr(VI) or Cr(III) were
      4.24% and 3.05%, respectively. The developed method was successfully applied to
      the speciation and determination of chromium species in water and urine samples.

PMID- 22967622
TI  - SPR evaluation of binding kinetics and affinity study of modified RNA aptamers
      towards small molecules.
AB  - Establishing an efficient method for evaluating the affinity changes after post
      SELEX modification of aptamers is essential for broadening the application of
      these oligonucleotides in biosensing. This is especially challenging when the
      ligand is a small molecule. Changes in affinity upon partial or total replacement
      of 2'-OH with 2'-OMe groups in the ribose moieties of a tobramycin binding RNA
      aptamer are described. The kinetic profile and binding properties of the
      different anti-tobramycin aptamers were measured by surface plasmon resonance
      (SPR) experiments through a real-time binding assay with the antibiotic
      covalently coupled to the gold sensor. This configuration maximizes the changes
      associated to the recognition event, which is otherwise undetectable. The results
      indicated that the modification slightly affects the binding characteristics of
      the parent RNA, while conferring biological stability to the aptamers against
      nucleases.

PMID- 22967623
TI  - Label-free fluorescence turn on detection of tiopronin with tunable dynamic range
      based on the ensemble of Alizarin Red S/copper ion.
AB  - In this study, a new type of rapid, label-free fluorescence turn-on assay for
      detection of tiopronin using Alizarin Red S (ARS)/copper ion ensemble is
      developed. ARS is high fluorescence in BR buffer solution. But, the fluorescence
      of ARS can be significantly quenched by copper ions due to ground-state
      complexation. However, in the presence of tiopronin, copper ions were released
      from the ARS and thus restored the fluorescence of ARS. The assay has several
      important features. First, the system is simple in design, fast in operation and
      is more convenient and promising than other methods. Second, the proposed assay
      eliminated the separation process and sophisticated instrumentations. Third, the
      detection process can be seen with the naked eye and can be easily adapted to
      automated high-throughput screening. At last, the assay has high sensitivity and
      selectivity for tiopronin and the detection limit is 0.8 ng/mL which is lower
      than or at least comparable to the previous methods. Moreover, the dynamic range
      of the sensor can be tuned simply by adjusting the concentration of copper ions.
      Importantly, the protocol offers high selectivity for the determination of
      tiopronin in pharmaceutical tablets, injection and biological samples with
      satisfactory results. Thus, the assay shows great potential applications in the
      fields of pharmaceuticals and clinical analysis.

PMID- 22967624
TI  - Evaluation of matrix effect in determination of some bioflavonoids in food
      samples by LC-MS/MS method.
AB  - In the present work the LC-MS/MS method with solid phase extraction for
      simultaneous determination of bioflavonoids rutin, quercetin, hesperidin,
      hesperetin and kaempferol in some food samples (red onion, orange peel and honey)
      was developed and the matrix effect accompanying this determination was
      quantified. The matrix effect evaluated using a postextraction addition method
      was found to be negative in the range -44 to -0.5%, indicating ionization
      suppression and strongly depended on bioflavonoid concentration. The observed
      matrix effect was explained taking into account the co-elution of phenolic acids,
      in terms of their acid-base and hydrophilic properties. The efficacy of
      extraction expressed as the absolute recoveries of flavonoids were 88-96%,
      indicating very good efficiency of extraction. The extracts of food samples
      obtained either by Soxhlet or ultrasonic extraction were analyzed for
      bioflavonoid content by the LC-MS/MS method in selected reaction monitoring mode
      using a triple quadrupole detector and standard addition method, which was found
      to be the most suitable calibration approach for these samples. The optimized
      separation was achieved on a Phenomenex Gemini C18 column with gradient elution
      and mobile phase composition A: 2% acetic acid in water and B: acetonitrile. R(s)
      values were in the range from 1.3 to 3.1, indicating good selectivity of the
      method. The obtained results (mg/100g fresh weight) for different bioflavonids
      were for rutin 0.16, for quercetin in the range 0.65-56, for hesperidin 0.016-24,
      for hesperetin 0.0068-36.4 and for kaempferol 0.14-1.63 and generally show good
      agreement with published data. Low detection limits (0.014-0.063 MUg/mL) were
      obtained with acceptable recoveries (86-114%). Total time of analysis was less
      than 40 min, therefore the proposed method represents significant improvement
      over existing methods.

PMID- 22967625
TI  - Rapid detection of illicit drugs in neat saliva using desorption/ionization on
      porous silicon.
AB  - The ability to detect illicit drugs directly in oral fluids is of major interest
      for roadside, workplace and athlete drug testing. For example, roadside testing
      for popular drugs of abuse is being rolled out by law enforcement agencies
      following the introduction of legislation in several countries all over the
      world. This paper reports on the direct analysis of methamphetamine, cocaine and
      3,4-methylenedioxymethamphetamine in oral fluids using a hydrophobic porous
      silicon array as a combined drug extraction and concentration medium. Analysis by
      laser desorption/ionization time-of-flight mass spectrometry (MS) identified
      these drugs with a sensitivity in line with the suggested confirmatory cut-off
      concentrations, and 300 times faster. In addition, MS imaging demonstrated good
      spot-to-spot reproducibility of the signal. Our analytical approach is compatible
      with multiplexing and is therefore suitable for high-throughput analysis of
      samples obtained from drug testing in the field. Furthermore, the application of
      this analytical technology is not limited to illicit drugs or oral fluids.
      Indeed, we believe that this platform technology could be applied to the high
      throughput analysis of diverse metabolites in body fluids.

PMID- 22967626
TI  - Characterizing the gas phase ion chemistry of an ion trap mobility spectrometry
      based explosive trace detector using a tandem mass spectrometer.
AB  - A commercial-off-the-shelf (COTS) ion trap mobility spectrometry (ITMS) based
      explosive trace detector (ETD) has been interfaced to a triple quadrupole mass
      spectrometer (MS/MS) for the purpose of characterizing the gas phase ion
      chemistry intrinsic to the ITMS instrument. The overall objective of the research
      is to develop a fundamental understanding of the gas phase ionization processes
      in the ITMS based ETD to facilitate the advancement of its operational
      effectiveness as well as guide the development of next generation ETDs. Product
      ion masses, daughter ion masses, and reduced mobility values measured by the
      ITMS/MS/MS configuration for a suite of nitro, nitrate, and peroxide containing
      explosives are reported. Molecular formulas, molecular structures, and ionization
      pathways for the various product ions are inferred using the mass and mobility
      data in conjunction with density functional theory. The predominant product ions
      are identified as follows: [TNT-H](-) for trinitrotoluene (TNT), [RDX+Cl](-) for
      cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), [NO(3)](-) for ethylene glycol
      dinitrate (EGDN), [NG+NO(3)](-) for nitroglycerine (NG), [PETN+NO(3)](-) for
      pentaerythritol tetranitrate (PETN), [HNO(3)+NO(3)](-) for ammonium nitrate
      (NH(4)NO(3)), [HMTD-NC(3)H(6)O(3)+H+Cl](-) for hexamethylene triperoxide diamine
      (HMTD), and [(CH(3))(2)CNH(2)](+) for triacetone triperoxide (TATP). The
      predominant ionization pathways for the formation of the various product ions are
      determined to include proton abstraction, ion-molecule attachment,
      autoionization, first-order and multi-order thermolysis, and nucleophilic
      substitution. The ion trapping scheme in the reaction region of the ITMS
      instrument is shown to increase predominant ion intensities relative to the
      secondary ion intensities when compared to non-ion trap operation.

PMID- 22967627
TI  - An amperometric sensor for the determination of benzophenone in food packaging
      materials based on the electropolymerized molecularly imprinted poly-o
      phenylenediamine film.
AB  - Benzophenone is one of the most commonly used photoinitiators of UV-cured inks on
      food packaging materials and can migrate into foodstuffs. In this study, an
      amperometric benzophenone sensor based on molecularly imprinted polymer (MIP) was
      successfully constructed for the first time. The sensor was prepared by
      electropolymerizing o-phenylenediamine (o-PD) on a glassy carbon electrode (GCE)
      in the presence of template benzophenone, and then removing the template by
      immersing the poly-o-phenylenediamine film-modified GCE in ethanol. The
      molecularly imprinted sensor was tested in the presence or absence of
      benzophenone by cyclic voltammetry and linear sweep voltammetry to verify the
      changes in the redox peak currents of potassium ferricyanide. The sensor
      responded sensitively to benzophenone over a linear range of 0.05-5 MUM with a
      detection limit of 10 nM. The imprinted sensor showed high recognition ability
      for benzophenone and was successfully applied to the determination of
      benzophenone in food packaging material samples.

PMID- 22967628
TI  - Synthesis of water-compatible imprinted polymers of in situ produced fructosazine
      and 2,5-deoxyfructosazine.
AB  - Fructosazine and 2,5-deoxyfructosazine are two natural chemicals with various
      applications as flavoring agents in food and tobacco industry; the 2,5
      deoxyfructosazine has also anti-diabetic and anti-inflammatory activities. In
      order to quantify these compounds in natural samples such as plant or food, we
      have developed a selective technique based on a water-compatible molecularly
      imprinted polymer (MIP). MIPs are prepared with a covalent approach from 2,5
      deoxyfructosazine as template formed in situ by the self-condensation of
      glucosamine with vinylphenyl boronic acid, taken as catalyst and covalent monomer
      during the pre-complexation step. Acrylamide and polyethylene glycol diacrylate
      are used as supplementary non-covalent functional monomer and cross-linker,
      respectively. For the first time, a highly cross-linked but highly polar
      imprinted polymer of fructosazine and deoxyfructosazine is obtained as a solid
      material and not a gel. Amount of monomers is optimized to obtain high
      selectivity for both molecules. Results show that the MIPs prepared have a
      significant imprinting effect with a resulting imprinting factor of 3 for both
      templates. Molecularly imprinted solid-phase extraction is then performed and
      could be used in routine analysis to extract 2,5-deoxyfructosazine and
      fructosazine from soy sauce.

PMID- 22967629
TI  - Fully automated ionic liquid-based headspace single drop microextraction coupled
      to GC-MS/MS to determine musk fragrances in environmental water samples.
AB  - A fully automated ionic liquid-based headspace single drop microextraction (IL-HS
      SDME) procedure has been developed for the first time to preconcentrate trace
      amounts of ten musk fragrances extensively used in personal care products (six
      polycyclic musks, three nitro musks and one polycyclic musk degradation product)
      from wastewater samples prior to analysis by gas chromatography and ion trap
      tandem mass spectrometry (GC-IT-MS/MS). Due to the low volatility of the ILs, a
      large internal diameter liner (3.4 mm i.d.) was used to improve the ILs
      evaporation. Furthermore, a piece of glass wool was introduced into the liner to
      avoid the entrance of the ILs in the GC column and a guard column was used to
      prevent analytical column damages. The main factors influencing the IL-HS-SDME
      were optimized. For all species, the highest enrichments factors were achieved
      using 1 MUL of 1-octyl-3-methylimidazolium hexafluorophosphate ([OMIM][PF(6)])
      ionic liquid exposed in the headspace of 10 mL water samples containing 300 g L(
      1) of NaCl and stirred at 750 rpm and 60  degrees C for 45 min. All compounds
      were determined by direct injection GC-IT-MS/MS with a chromatographic time of 19
      min. Method detection limits were found in the low ng mL(-1) range between 0.010
      ng mL(-1) and 0.030 ng mL(-1) depending on the target analytes. Also, under
      optimized conditions, the method gave good levels of intra-day and inter-day
      repeatabilities in wastewater samples with relative standard deviations varying
      between 3% and 6% and 5% and 11%, respectively (n=3, 1 ng mL(-1)). The
      applicability of the method was tested with different wastewater samples from
      influent and effluent urban wastewater treatment plants (WWTPs) and one potable
      treatment plant (PTP). The analysis of influent urban wastewater revealed the
      presence of galaxolide and tonalide at concentrations of between 2.10 ng mL(-1)
      and 0.29 ng mL(-1) and 0.32 ng mL(-1) and <MQL (Method Quantification Limit),
      respectively; while the remaining polycyclic musks concentrations were below the
      method quantification limits and two of the nitro musks (musk xylene and musk
      moskene) were not detected. The analysis of effluent urban wastewater showed a
      decrease in galaxolide and tonalide concentrations while the other target
      analytes were not detected. In waters from PTP only galaxolide was found at a
      concentration higher than MQL.

PMID- 22967630
TI  - Molecular imprinting technology for specific recognition of heparan sulfate like
      disaccharides.
AB  - Iinteractions of biologically active proteins with sulfated glycans, particularly
      heparan sulfates (HS), are dependent on factors involving amounts and positions
      of the sulfate groups in the sugars chains. Although the importance of knowing
      the exact positions of the sulfate groups in particular HS sequences is well
      recognized, at present, approaches in this area are complex and still considered
      as a challenge. Here, we investigated the applicability of the 'Molecular
      Imprinting Technology' for the generation of imprinted polymers able to
      specifically recognize a model HS-like disaccharide. In order to advance on the
      applicability of this technology to the recognition of these complex sugars, we
      prepared a library of imprinted polymers to investigate the impact of the
      polymerization reaction conditions and stoichiometry on the generation of binding
      sites able to specifically recognize the model sulfated sugar. Our results show
      that imprinted polymers able to specifically bind HS-like saccharide can readily
      be obtained. This constitutes a suitable option for developing novel strategies
      directed to study fine sulfated sugars structures.

PMID- 22967631
TI  - A highly sensitive and automated method for the determination of hypoxanthine
      based on lab-on-valve approach using Fe3O4/MWCNTs/beta-CD modified electrode.
AB  - A Fe(3)O(4)/multiwall carbon nanotubes/beta-cyclodextrin (Fe(3)O(4)/MWCNTs/beta
      CD) modified electrode, for highly sensitive and automated hypoxanthine
      measurements, was developed in a sequential injection lab-on-valve system. The
      electrochemical oxidation behavior of hypoxanthine was investigated in phosphate
      buffer solution by cyclic voltammetry and linear sweep voltammetry. The
      Fe(3)O(4)/MWCNTs/beta-CD modified electrode exhibits preferably analytical
      characteristics in electrocatalytic activity towards the oxidation of
      hypoxanthine. Under optimized conditions, the log oxidation peak current
      intensity was proportional to log hypoxanthine concentration covering the range
      from 5.0*10(-8) to 1.0*10(-5) mol L(-1) with a correlation coefficient of 0.9965.
      A detection limit of 0.3*10(-8) mol L(-1) was achieved along with a sampling
      frequency of 20 h(-1). This hyphenated system offers some advantages in terms of
      rapidness, sensitivity and ease of manipulation. Its further applications were
      utilized for the determination of hypoxanthine in meat samples.

PMID- 22967632
TI  - Dispersive liquid-liquid microextraction with non-halogenated extractants for
      trihalomethanes determination in tap and swimming pool water.
AB  - An effective, low solvent consumption, reduced cost and high throughput sample
      preparation method for the determination of four trihalomethanes (THMs) in tap
      and swimming pool water samples is presented. THMs extraction and concentration
      were performed by dispersive liquid-liquid microextraction (DLLME), based on the
      use of non-halogenated and low volatile solvents as extractants. Analytes were
      further determined by gas chromatography with micro-electron capture detection
      (GC-microECD). Under optimized conditions, the proposed method uses 18 mL volume
      samples, 0.7 mL of acetone (dispersant) and 0.05 mL of 1-undecanol (extractant).
      Achieved enrichment factors (EFs) varied from 67 to 104 times, the limits of
      quantification (LOQs) stayed between 0.05 and 1.3 ng mL(-1), and an excellent
      linearity was noticed up to 100 ng mL(-1). Relative recoveries, measured for
      spiked aliquots of tap and swimming pool water samples, remained between 79% and
      113%, with associated standard deviations below 12%. The applicability of the
      developed methodology was demonstrated with chlorinated water samples analysis.
      As regards tap water samples, the sum of THMs concentrations remained under the
      limit fixed by the European Union (100 ng mL(-1)); however, some samples
      contained levels close to 80 ng mL(-1), the maximum allowable concentration
      established by the United States Environmental Protection Agency (EPA).

PMID- 22967633
TI  - Multi-element determination of Pt, Pd and Ir traces in environmental samples by
      ICP-MS after pre-concentration.
AB  - An automated flow analysis method with on-line column pre-concentration/
      inductively coupled plasma mass spectrometry (ICP-MS) was developed for the
      simultaneous determination of Pt, Pd and Ir in environmental samples. The system
      is based on retention of the analytes onto a column filled with 1,5-bis (2
      pyridyl)-3-sulphophenyl methylene thiocarbonohydrazide immobilized on an
      aminopropyl-controlled pore glass (PSTH-cpg) placed in the injection valve of a
      simple flow manifold. The retained platinum group metals (PGMs) were subsequently
      eluted with a mixture of HNO(3) and thiourea. The effects of chemicals and flow
      variables were investigated. The optimized operating conditions were: sample pH
      3.2, sample flow rate: 1.1 mL min(-1); eluent flow rate: 2.1 mL min(-1) and
      eluent 0.03% m/v thiourea solution in 3.2% (v/v) HNO(3). The detection limits
      obtained were 78.5 ng L(-1) for Pt, 55.5 ng L(-1) for Pd and 0.1 ng L(-1) for Ir.
      The enrichment factors were 18, 2.3 and 43 for Pt, Pd and Ir, respectively. The
      accuracy of the method was checked by the analysis of certified reference
      materials and by determining the analytes content in spiked environmental
      samples. Recovery was found to be in the range 93-107% in all cases.

PMID- 22967634
TI  - Mercury speciation analysis in terrestrial animal tissues.
AB  - No previous analytical procedures are available and validated for mercury
      speciation analysis in terrestrial animal tissues. This analysis is a difficult
      task both because the expected concentrations are low, since important
      accumulation process are not likely to occur, and also because there are not
      commercially available certified reference material. Thus, an analytical
      methodology has been developed and validated for mercury speciation for the
      specific case of terrestrial animal tissues. The proposed method is based on the
      quantitative extraction of the species by closed-vessel microwave assisted
      heating with an alkaline reagent, followed by ethylation. The ethylated
      derivatives were then submitted to head-space solid phase microextraction with a
      100 MUm polidimethylsiloxane-coated fiber, and desorbed onto a gas chromatograph
      coupled to atomic fluorescence detection via pyrolysis unit (HS-SPME-GC-pyro
      AFS). Procedural detection limits were 31.8 ng g(-1) and 52.5 ng g(-1) for
      CH(3)Hg(+) and Hg(2+), respectively, for liver and 35.3 ng g(-1) and 58.1 ng g(
      1) for CH(3)Hg(+) and Hg(2+), respectively, for kidney. These limits of detection
      are 5.5 and 6 times better than the obtained without solid phase microextraction
      for CH(3)Hg(+) and Hg(2+), respectively. The methodology was found linear up to
      120 MUg L(-1) and reproducible from one day to the following. It was validated
      with certified reference materials NCS ZC 71001 (beef liver) and BCR No 186 (pig
      kidney) for total mercury, calculated as the sum of species, and with spiked red
      deer liver and kidney for speciation. Finally, it was applied to the analysis of
      samples of red deer liver, red deer kidney and wild boar kidney coming from the
      Almaden's mercury mining area (Ciudad Real, Spain), the longest and largest
      producer of mercury in the world until its closure in 2002.

PMID- 22967636
TI  - Feasibility for quantitative determination of deoxyribonucleic acid by using near
      infrared diffuse reflectance spectroscopy.
AB  - A method for quantitative determination of fish sperm deoxyribonucleic acid
      (fsDNA) in solutions was developed by using adsorption preconcentration and near
      infrared diffuse reflectance spectroscopy (NIRDRS). A high capacity adsorbent of
      amino-modified silica particle (AMSP) was prepared for preconcentration of fsDNA
      in solutions. Under the optimized conditions, the adsorption rate can be above
      90% within 3 min. After adsorbing the DNA onto the adsorbent, near-infrared (NIR)
      spectra in diffuse reflectance mode were measured and partial least squares (PLS)
      model was established for fast quantitative prediction. The results show that the
      correlation coefficient (R) between the predicted and the reference concentration
      is 0.9894 and the recoveries are in the range of 92.9-123.4% for the validation
      samples in the concentration range of 3.00-29.38 mg L(-1). Therefore, the
      feasibility for quantitative analysis of DNA in solutions by NIRDRS is proved.
      This may provide an alternative way for fast determination of DNA in solutions.

PMID- 22967635
TI  - High performance of hydrogen peroxide detection using Pt nanoparticles-dispersed
      carbon electrode prepared by pulsed arc plasma deposition.
AB  - We propose novel electrodes with platinum nanoparticles dispersed on a glassy
      carbon (Pt-NPs/GC) prepared using a pulsed arc plasma deposition (APD) method.
      The method could coat Pt-NPs on a base material directly with a single-step
      process in a very short deposition time. The characteristics of the electrodes
      were discussed in detail. The detection of hydrogen peroxide was performed as an
      example for application of the electrodes. The distribution of nanoparticles was
      controlled easily by the number of pulse. The surface morphology changed with the
      pulse number and the annealing except for the sample prepared by 5 pulses
      deposition (APD(5)), implying that the APD(5) remained as NPs after the
      annealing. Average particle size was 2.7 nm on the Pt-NPs/GC. Catalyst activity
      for oxidizing hydrogen peroxide per Pt loading was excellent on the Pt-NPs/GC.
      When the Pt-NPs/GC was used as a detector for hydrogen peroxide on a flow
      injection analysis, the Pt-NPs/GC showed high sensitivity without deterioration.
      Oxidation current increased linearly with the concentration of hydrogen peroxide
      from 10nM to 100 MUM. This fast and easily prepared electrode showed the
      capability to replace a conventional bulk metal electrode.

PMID- 22967637
TI  - Ultrasound-assisted ionic liquid/ionic liquid-dispersive liquid-liquid
      microextraction for the determination of sulfonamides in infant formula milk
      powder using high-performance liquid chromatography.
AB  - Ultrasound-assisted ionic liquid/ionic liquid-dispersive liquid-liquid
      microextraction (UA-IL/IL-DLLME) high-performance liquid chromatography was
      developed and applied to the extraction, separation and determination of
      sulfonamides in infant formula milk powder samples. The hydrophobic IL and
      hydrophilic IL were used as extraction solvent and dispersion solvent,
      respectively. The extraction procedure was induced by the formation of cloudy
      solution, which was composed of fine drops of [C(6)MIM][PF(6)] dispersed entirely
      into sample solution with help of [C(4)MIM][BF(4)]. The purification of sample
      and concentration of target analytes were performed simultaneously. The
      introduction of ion-pairing agent (NH(4)PF(6)) was beneficial to the improvement
      of recoveries for IL phase and analytes. The experimental parameters of the UA
      IL/IL-DLLME, including concentration of [C(6)MIM][PF(6)] and [C(4)MIM][BF(4)] in
      sample solution, ultrasound extraction time, pH value of sample solution and
      amount of ion-pairing agent (NH(4)PF(6)), were evaluated. The limits of detection
      for sulfamerazine, sulfamethizole, sulfachlorpyridazine, sulfamonomethoxine,
      sulfmethoxazole and sulfisoxazole were 2.94, 9.26, 16.7, 5.28, 3.35 and 6.66 MUg
      kg(-1), respectively. When the present method was applied to the analysis of
      infant formula milk powder samples, the recoveries of the analytes ranged from
      90.4% to 114.8% and relative standard deviations were lower than 7.5%. The
      proposed method was compared with the ionic liquid-homogeneous liquid-liquid
      microextraction, ionic liquid-ultrasound-assisted emulsification-microextraction
      and ionic liquid-temperature-controlled-DLLME. The results indicated that the
      proposed method is effective for the extraction of the sulfonamides in milk
      powder samples.

PMID- 22967638
TI  - Flow injection simultaneous determination of synthetic colorants in food using
      multiple pulse amperometric detection with a boron-doped diamond electrode.
AB  - A single-line flow injection system and multiple pulse amperometric detection
      using a boron-doped diamond electrode were employed to develop and optimize a
      simple, low-cost, and rapid method for the simultaneous determination of two
      pairs of food colorants: tartrazine and sunset yellow (TT-SY) or brilliant blue
      and SY (BB-SY). A dual-potential waveform was used: E(det.1)=-150 mV (400 ms
      duration) and E(det.2)=-450 mV (100 ms duration) vs. Ag/AgCl (3.0 mol L(-1) KCl).
      Polarization at E(det.1) or E(det.2) causes reduction of SY or the respective
      pair of colorants, TT-SY or BB-SY; hence, with proper current correction, both
      colorants in each pair can be determined. The obtained linear response ranges
      (detection limits) were 5.0-60.0 (2.5) and 1.0-50.0 (0.80) MUmol L(-1), for TT
      and SY, or 5.0-60.0 (3.5) and 1.0-50.0 (0.85) MUmol L(-1), for BB and SY,
      respectively. Investigation of possible interferents (other food colorants or
      additives) showed no significant interference with the methods here proposed,
      which were then used to simultaneously determine the pairs of colorants in
      industrialized food samples, with results that showed good agreement with those
      obtained using a comparative HPLC method.

PMID- 22967639
TI  - A stable and reproducible nanosilver-aggregation-4-mercaptopyridine surface
      enhanced Raman scattering probe for rapid determination of trace Hg2+.
AB  - A stable nanosilver solution was prepared, using PEG10000 as stabilizer and
      NaBH(4) as reducer. In pH 6.6 Na(2)HPO(4)-NaH(2)PO(4) buffer solution containing
      PEG10000 and NaCl, the nanosilvers (AgNPs) were aggregated to form the stable
      nanosilver-aggregation (AgNPA) that could conjugate with 4-mercaptopyridine (MPy)
      to obtain an AgNPA-MPy surface-enhanced Raman scattering (SERS) probe with a
      strong SERS peak at 1097 cm(-1). When Hg(2+) concentration increased, the SERS
      intensity at 1097 cm(-1) decreased linearly as the stable complex of
      [Hg(MPy)(2)](2+) was formed and the AgNPA particles precipitate to the bottom.
      The decreased SERS intensity was linear to Hg(2+) concentration in the range of
      50-3000 nmol/L. Based on this, a new sensitive SERS method has been proposed for
      the determination of trace Hg(2+) in the water sample, with satisfactory results.

PMID- 22967640
TI  - Selective extraction and determination of catecholamines in urine samples by
      using a dopamine magnetic molecularly imprinted polymer and capillary
      electrophoresis.
AB  - A rapid and selective method for the extraction and determination of
      catecholamines (CLs) from urine samples has been successfully developed using a
      magnetic molecularly imprinted polymer (MMIP) as a sorbent material. The MMIP has
      been prepared using dopamine hydrochloride (DA) as template molecule, methacrylic
      acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EDMA) as cross
      linking agent and Fe(3)O(4) magnetite as magnetic component. The extraction was
      carried out by stirring urine samples with the magnetic polymer. When the
      extraction was completed, the MMIP, together with the captured analytes, was
      easily separated from the sample matrix by an adscititious magnet. The analytes
      desorbed from the MMIP were determined by capillary electrophoresis (CE). It was
      shown that the MMIP had high affinity and selectivity toward DA and other
      structurally related CLs such as 3-methoxytyramine hydrochloride (MT), DL
      normetanephrine hydrochloride (NME), DL-norephinephrine hydrochloride (NE) and
      (+/-) epinephrine (E). Different parameters affecting the extraction efficiency
      were evaluated in order to achieve the optimal pre-concentration of the analytes
      and to reduce non-specific interactions. Under the optimal conditions, the CL
      limits of detection were at the 0.04-0.06 MUM range. The relative standard
      deviations of migration time and response ranged from 0.7% to 1.4% and from 2.9%
      to 5.5%, respectively. The proposed method was successfully applied to determine
      CLs, including MT, NME, DA, NE and E in human urine samples.

PMID- 22967641
TI  - Following butter flavour deterioration with an acoustic wave sensor.
AB  - Off-flavours develop naturally in butter and the process is accelerated by heat.
      An acoustic wave sensor was used to detect the aroma compounds evolved from
      heated butter and the results have shown that registered marked changes were
      coincident to odour changes detected by sensory analysis. The flavour compounds
      have also been analysed by GC/MS for identification. The response of the sensor
      was fully characterized in terms of the sensitivity to each of the identified
      compounds, and sensitivities of the system SPME/sensor were compared with the
      sensitivities of the system SPME/GC/MS. It was found that the sensor analytical
      system was more sensitive to methylketones than to fatty acids. The SPME/GC/MS
      system also showed the highest sensitivity to 2-heptanone, followed by 2
      nonanone, but third place was occupied by undecanone and butanoic acid, to which
      the sensor showed moderate sensitivity. 2-heptanone was found to be an
      appropriate model compound to follow odour changes till the 500 h, and the lower
      sensitivity of the sensor to butanoic acid showed to be a positive
      characteristic, as saturation was prevented, and other more subtle changes in the
      flavour could be perceived.

PMID- 22967642
TI  - Characterization of CMPO and its radiolysis products by direct infusion ESI-MS.
AB  - Direct infusion electrospray ionization mass spectrometry (ESI-MS) approaches
      were developed for rapid identification of impurity compounds formed from
      octylphenyl-(N,N-(diisobutyl)carbamoylmethyl) phosphine oxide (CMPO) during alpha
      and gamma irradiation experiments of this compound in dodecane. CMPO is an
      aggressive Lewis base, and produces extremely abundant metal complex ions in the
      ESI-MS analysis that make identification of low abundance compounds that are less
      nucleophilic challenging. Radiolysis products were identified using several
      approaches including restricting ion trapping so as to exclude the abundant
      natiated CMPO ions, extraction of acidic products using aqueous NaOH, and
      extraction of basic products using HNO(3). These approaches generated protonated,
      natiated and deprotonated species derived from CMPO degradation products formed
      via radiolytic cleavages of several different bonds. Cleavages of the amide and
      methylene-phosphoryl bonds appear to be favored by both alpha and gamma
      irradiation, while alpha irradiation also appears to induce cleavage of the
      methylene-carbonyl bond. The degradation products observed are formed from
      recombination of the initially formed radicals with hydrogen, methyl, isopropyl
      and hydroxyl radicals that are derived either from CMPO, contacted aqueous nitric
      acid, or the dodecane solvent.

PMID- 22967643
TI  - Carbon nanotubes as a solid sorbent for the preconcentration of Cr, Mn, Fe, Co,
      Ni, Cu, Zn and Pb prior to wavelength-dispersive X-ray fluorescence spectrometry.
AB  - The preconcentration of trace elements on multiwalled carbon nanotubes (MWCNTs)
      followed by a wavelength-dispersive X-ray fluorescence analysis (WDXRF) has been
      investigated. The proposed preconcentration procedure is based on the sorption of
      trace elements on MWCNTs dispersed in analyzed solution. After sorption, the
      MWCNTs with the metal ions were collected onto the filter, and then the
      preconcentrated elements were determined directly by WDXRF. The preconcentration
      method was optimized, and in consequence, in order to obtain satisfactory
      recoveries using 100 mL of samples, the sorption process was performed with 1mg
      of MWCNTs within 5 min. Some conditions of the preconcentration process such as
      the pH of analyte solution, amounts of MWCNTs, the volume of the sample, the
      contact time between analytes and MWCNTs (stirring time), and the effects of
      foreign metals are discussed in detail in the paper. Adsorption onto raw and
      oxidized MWCNTs was also studied. The proposed procedure allows obtaining the
      detection limits of 0.6, 0.6, 1.0, 0.7, 0.6, 0.5, 0.9 and 1.9 ng mL(-1) for
      Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Pb(II),
      respectively. The recoveries of determined elements were about 100%. Because the
      analytes are not eluted from the sorbent before WDXRF analysis, the risk of
      contamination and loss of analytes is reduced to minimum. Moreover, because the
      samples are analyzed as a thin layer, the matrix effects can be neglected. The
      proposed preconcentration method using MWCNTs coupled with WDXRF spectrometry was
      successfully applied to determine trace elements in natural water samples.

PMID- 22967644
TI  - Electrochemical determination of olmesartan medoxomil using hydrothermally
      prepared nanoparticles composed SnO2-Co3O4 nanocubes in tablet dosage forms.
AB  - Low-dimensional nanoparticles composed SnO(2)-Co(3)O(4) nanocubes (NCs) were
      prepared by a hydrothermal method using reducing agents. The doped nanomaterials
      were investigated by UV/vis, powder X-ray diffraction, FT-IR, energy-dispersive X
      ray spectroscopy (EDS), and Raman spectroscopy, and field-emission scanning
      electron microscopy. They were deposited on a silver electrode (AgE, surface
      area, 0.0216 cm(2)) to give a drug sensor with a fast response towards Olmesartan
      medoxomil (OSM) in 0.1 mol L(-1) phosphate buffer-phases. The sensor also
      exhibits higher sensitivity, long-term stability, and enhanced electrochemical
      response. The calibration plot is linear (r(2)=0.9948) over the 0.28 nmol L(-1)
      1.4 MUM OSM concentration range. The sensitivity is ~2.083 MUA cm(-2) mmol L(-1)
      and the detection limit is 0.17 nmol L(-1) (at an SNR of 3). We discuss the
      possible potential uses of this nanoparticles doped semiconductor NCs in terms of
      drug sensing, which could also be employed for the determination of drugs in
      quality control of formulation.

PMID- 22967645
TI  - Microwave-assisted extraction in combination with capillary electrophoresis for
      rapid determination of isoquinoline alkaloids in Chelidonium majus L.
AB  - A simple and rapid method based on microwave-assisted extraction (MAE) followed
      by capillary electrophoresis (CE) was developed for the quantification of eight
      isoquinoline alkaloids in Chelidonium majus L. (Ch. majus). The key parameters
      affecting CE separation and MAE extraction were investigated and optimized.
      Complete separation of eight alkaloids was achieved within only 9 min using a 500
      mM Tris-H(3)PO(4) buffer (pH 2.5) containing 50% (v/v) methanol and 2mM HP-beta
      cyclodextrin. The optimal MAE extraction was performed at 60  degrees C for 5 min
      with methanol-water-HCl (90:10:0.5, v/v/v) as the extracting solvent, which gave
      much higher extraction efficiency in significantly shorter time than conventional
      heat reflux extraction (HRE) and ultrasonic extraction (USE) methods. Good
      linearities were obtained for all the alkaloids investigated with correlation
      coefficients above 0.9994. The repeatability and intermediate precision were less
      than 4.11% and the recoveries ranged from 98.0% to 103.9%. The developed method
      was successfully applied to 14 Ch. majus samples obtained from different regions
      of China. Compared with previously reported methods, the present method offers a
      dramatic savings in overall analysis time and considerable reduction in solvent
      consumption.

PMID- 22967646
TI  - Quantum dot-Eu3+ conjugate as a luminescence turn-on sensor for ultrasensitive
      detection of nucleoside triphosphates.
AB  - We report a conjugate of thioglycolic acid (TGA) capped CdTe quantum dot and
      Eu(3+) ion (TGA-CdTe QD-Eu(3+)) that can be used as an ultrasensitive
      luminescence turn-on sensor for nucleoside triphosphates (NTPs). The TGA-CdTe QD
      Eu(3+) conjugate is a weakly luminescent species as a result of the strong
      quenching effect of Eu(3+) ion on the luminescence of TGA-CdTe QDs. The
      conjugate's luminescence can be readily restored by its reaction with adenosine
      triphosphate (ATP) and other NTPs, and thus gives an ultrasensitive detection of
      NTPs, with a detection limit of 2 nM. The sensing mechanism has also been
      explored, and the effective quenching of TGA-CdTe QDs emission by Eu(3+) ions has
      been attributed to photoinduced electron transfer (PET). ATP, as the
      representative of NTPs, can remove Eu(3+) from the surface of TGA-CdTe QDs,
      leading to restoration of the TGA-CdTe QDs luminescence.

PMID- 22967647
TI  - Evaluation of isostructural metal-organic frameworks coated capillary columns for
      the gas chromatographic separation of alkane isomers.
AB  - Isostructural metal-organic frameworks (MOFs) MIL-100(Fe) and MIL-100(Cr), which
      have identical organic linker and Mobil Thirty-Nine zeolitic type, but different
      metal ions, were exploited as stationary phases for capillary gas chromatographic
      separation of alkane isomers. MIL-100(Fe) coated capillary column showed great
      capability and high efficiency for the gas chromatographic separation of alkane
      isomers without the need of temperature-programming, while MIL-100(Cr) coated
      capillary column gave poor performance for the separation. The separation
      performance of MIL-100(Fe) coated capillary column was even better than
      commercial HP-5MS and GS-GasPro capillary columns. The determined McReynolds
      constants, adsorption enthalpies and entropies showed that MIL-100(Fe) coated
      capillary column gave relatively weaker interaction with alkane isomers than MIL
      100(Cr) coated capillary column. The relative standard deviations of
      repeatability for C7 alkane isomers on MIL-100(Fe) coated capillary column were
      0.06-0.16%, 1.1-1.5%, 2.8-3.0% and 2.1-2.4% for retention time, half peak width,
      peak height and peak area, respectively.

PMID- 22967648
TI  - Development of a novel europium(III) complex-based luminescence probe for time
      resolved luminescence imaging of the nitric oxide production in neuron cells.
AB  - Nitric oxide (NO) is a signaling molecule, and plays an important role in some
      human neuroses. In this work, a novel europium(III) complex, [4'-(3-methylamino-4
      aminophenoxy)-2,2':6',2''-terpyridine-6,6''-diyl] bis(methylenenitrilo)
      tetrakis(acetate)-Eu(3+) (MATTA-Eu(3+)), has been designed and synthesized as a
      luminescent probe for the time-resolved luminescence detection of NO. The complex
      itself is weakly luminescent, but can specifically react with NO under the
      aerobic conditions to form its triazole derivative, [4'-(3-methyl-4-benzotriazol
      6-yl-oxy)-2,2':6',2''-terpyridine-6,6''-diyl] bis(methylenenitrilo)
      tetrakis(acetate)-Eu(3+) (MBTTA-Eu(3+)), accompanied by a remarkable luminescence
      enhancement with a long luminescence lifetime. The luminescence response of the
      complex to NO is rapid, highly selective and sensitive, and pH-insensitive in
      aqueous solutions. These properties enable MATTA-Eu(3+) to be used as a turn-on
      luminescent probe for the selective recognition and sensitive time-resolved
      luminescence detection of NO in a wider pH range. The probe-loaded PC12 cells
      were prepared, and used for the time-resolved luminescence imaging detection of
      the glutamate-induced NO production in the cells. The result demonstrated the
      practical utility of the probe for imaging the NO production in neuron cells.

PMID- 22967649
TI  - Molecularly imprinted polymers based on multi-walled carbon nanotubes for
      selective solid-phase extraction of oleanolic acid from the roots of kiwi fruit
      samples.
AB  - This study describes the synthesis of novel molecularly imprinted polymers based
      on multi-walled carbon nanotubes (MWNTs@MIPs) using oleanolic acid as the
      template, 4-vinylpyridine as the functional monomer and divinylbenzene as the
      cross-linker by heat-induced polymerization. The MWNTs@MIPs were characterized
      with Fourier transform infrared (FT-IR) spectrometry and scanning electron
      microscopy (SEM). The adsorption process of the MWNTs@MIPs towards oleanolic acid
      was investigated in detail. The properties of MWNTs@MIPs for solid-phase
      extraction (SPE) were also evaluated. The results demonstrated the good
      imprinting effect and the comparable selectivity of MWNTs@MIPs. The optimized
      molecularly imprinted solid-phase extraction (MISPE) procedure was applied to
      extract oleanolic acid from the extracts of the roots of kiwi fruit samples. The
      recoveries of spiked oleanolic acid in kiwi fruit samples were in the range of 84
      92.6% with relative standard deviations below 5%, and its limit of detection
      reached 2.56 MUg L(-1).

PMID- 22967650
TI  - "Induced fit" recognition of proteins by surface imprinted silica with "soft"
      recognition sites.
AB  - Molecular imprinting is a useful method to make enzyme mimics for protein
      recognition. Classic protein imprinting involves entrapping proteins within
      polysiloxane or polyacrylamide, but due to the rigidity of the recognition sites
      and the limited interaction between proteins and small molecule monomers, they
      often have unsatisfactory capacity, poor reproducibility and low specificity. In
      this report, "soft" and flexible recognition sites that can allow "induced fit"
      of the target proteins were created by a novel surface imprinting technique. When
      about 25% of the template proteins were removed, the unremoved proteins created
      "soft" and flexible loops that can lock into place upon protein rebinding, which
      provides additional favorable interactions between the rebind proteins and the
      imprinted sites. The adsorption capacity of the surface imprinted silica is
      24.8*10(-7) mol/g. The "soft" recognition sites can distinguish target hemoglobin
      from other proteins such as bovine serum albumin, Cytochrome C and RNase A.

PMID- 22967651
TI  - An in-situ extraction-preconcentration method using ionic liquid-based
      surfactants for the determination of organic contaminants contained in marine
      sediments.
AB  - The determination of a group of organic contaminants from marine sediments
      samples including three polycyclic aromatic hydrocarbons, five alkylphenols
      (i.e., bisphenol-A or nonylphenol) and one paraben has been carried out using an
      extraction/preconcentration strategy with ionic liquid-based surfactants and high
      performance liquid chromatography (HPLC) with diode array detection (DAD).
      Sediments are first extracted using two IL-based surfactants, specifically 1
      hexadecyl-3-methyl imidazolium bromide (C(16)MIm-Br) and 1-hexadecyl-3-butyl
      imidazolium bromide (C(16)C(4)Im-Br), as the extraction media in a microwave
      assisted extraction (MAE) procedure, followed by a novel in situ preconcentration
      method. The optimized MAE method requires 0.1 g of sediment and 5 mL of 40 mM
      C(16)MIm-Br IL solution. The extracts are then centrifuged and filtered. The
      subsequent preconcentration in situ approach consists of the insolubilization of
      an IL-based surfactant formed by a metathesis reaction using the anion-exchange
      reagent lithium bis[(trifluoromethane)sulfonyl]imide (LiNTf(2)), which produces
      an analyte enriched IL microdroplet. The optimized in situ approach utilizes 4 mL
      of the filtered extract, which are mixed with acetonitrile and 92 MUL of LiNTf(2)
      solution (0.5 g mL(-1)), heated, vortexed and centrifuged. The formed IL
      microdroplet is then simply diluted with acetonitrile (~100 MUL) and injected in
      the chromatograph without any further clean-up steps. The overall
      extraction/preconcentration method requires approximately 25 min in spite of
      dealing with complex solid samples, is nearly free of organic solvent (requires
      ~900 MUL of acetonitrile per sample), and produces high preconcentration factors
      and quantification limits down to 0.04 mg kg(-1) using HPLC-DAD.

PMID- 22967652
TI  - A novel and simple strategy for simultaneous determination of dopamine, uric acid
      and ascorbic acid based on the stacked graphene platelet nanofibers/ionic
      liquids/chitosan modified electrode.
AB  - A promising electrochemical sensor for simultaneous determination of dopamine
      (DA), uric acid (UA) and ascorbic acid (AA) was fabricated based on the stacked
      graphene platelet nanofibers (SGNF)/ionic liquid (IL)/chitosan (CS) modified
      electrode. The SGNF/IL/CS modified electrode possessed excellent electrocatalytic
      activity towards the oxidation of DA, UA and AA with obvious reduction of over
      potential and increased peak current, and the separations of oxidation peak
      potentials of DA-UA, DA-AA, and UA-AA were of 151, 213 and 364 mV, respectively.
      Under the optimum conditions, the linear range for the detection of DA, UA and AA
      were 0.05-240, 0.12-260, and 30-350 MUM with the lowest detection limits of 0.05,
      0.10 and 14.8 MUM for DA, UA and AA, respectively. In addition, the
      electrochemical sensor showed high sensitivity, excellent selectivity,
      reproducibility and long-term stability.

PMID- 22967653
TI  - Evaluation of a silver-based electrocatalyst for the determination of hydrogen
      peroxide formed via enzymatic oxidation.
AB  - Silver paste electrodes modified with lyotropic phases formed from dodecyl
      benzenesulphonic acid and KCl were used as the reductant in the determination of
      the hydrogen peroxide released from the enzymatic reaction of glucose oxidase
      with glucose and oxygen. The response of the modified electrode to hydrogen
      peroxide reduction (-0.1 V vs. Ag/AgCl) was shown to suffer from interference
      resulting from co-localization of enzyme and substrate at the electrode surface.
      This interference was eradicated by the introduction of a perm-selective membrane
      in the form of cellulose acetate. This further facilitated immobilization of the
      enzyme while allowing diffusion of the generated peroxide to the electrode. The
      resulting configuration was shown to be capable of the analytical determination
      of glucose.

PMID- 22967654
TI  - "From safe source to safe sink" development of colorimetric assay for gabapentin
      in bulk drug and capsules using naturally derived genipin.
AB  - A novel colorimetric assay for gabapentin in bulk drug and capsules has been
      developed via a safety-and-sustainability concerning concept. The method relied
      on the reaction of primary amino group of drug with non-toxic and eco-friendly
      genipin in totally aqueous medium to form the blue product which was subsequently
      measured by visible spectrophotometry at 590 nm. Under the optimized conditions,
      Beer's law was obeyed in the concentration range of 0.15-0.50 mM (r(2)=0.9998).
      It was accurate, precise and insensitive to the interferences from all related
      compounds specified in the United States Pharmacopeia as well as commonly used
      excipients. Furthermore, it gave the assay results in agreement with the
      pharmacopeial chromatographic method. Owing to the environmental concern and
      responsibility, a fast and facile method was also proposed for the treatment of
      waste generated from the assay based on the decoloration by using gypsum as a
      cheap and commonly available adsorbent. After the treatment, more than 95% of the
      initial blue product was removed from the waste solution and the treated waste
      was proven to be safe for aquatic organisms, as studied in brine shrimp and guppy
      fishes. Therefore, this work not only reports for the first time the application
      of naturally derived genipin to drug analysis, but also presents a new and
      contemporary paradigm that illustrates the fully benign-by-design development of
      the analytical methodologies in the era of Green Chemistry, starting from the
      safe source of reagents toward the safe sink when waste is released into the
      environment.

PMID- 22967655
TI  - Simultaneous derivatization and dispersive liquid-liquid microextraction of
      anilines in different samples followed by gas chromatography-flame ionization
      detection.
AB  - A new method based on simultaneous derivatization and dispersive liquid-liquid
      microextraction in one step is developed for determination of five anilines in
      different aqueous samples. In this method, acetonitrile containing microlitre
      level of butylchloroformate was rapidly injected into aqueous sample by a
      syringe. After centrifugation of the cloudy solution, the fine droplets of the
      butylchloroformate containing the derivatized analytes were sedimented in the
      bottom of the conical test tube. Then, 0.5 MUL of the settled phase was injected
      into gas chromatography-flame ionization detector. Under optimum conditions the
      enrichment factors, extraction recoveries and enhancement factors were high and
      ranged between 197 and 298, 47 and 69%, and 4.7 and 6.2, respectively. Linearity
      was observed in the range of 10-10,000 MUg L(-1) (except for 4-chloroaniline),
      and the relative standard deviations (RSD %) were lower than 5.2% (n=6). The
      limits of detection of the six anilines ranged from 1 to 3 MUg L(-1). Different
      aqueous samples including tap, river and well waters as well as wastewaters were
      successfully analyzed. In this method the extraction solvent and derivatization
      agent are the same and the derivatization reaction was carried out under mild
      conditions. This method has several advantages over other reported techniques,
      being very simple, rapid and less hazardous for the environment.

PMID- 22967656
TI  - Multi-class determination of personal care products and pharmaceuticals in
      environmental and wastewater samples by ultra-high performance liquid
      chromatography-tandem mass spectrometry.
AB  - In this work, a multi-class method for the simultaneous determination of 17
      emerging contaminants, including pharmaceuticals and personal care products, has
      been developed. Target analytes were two anti-inflammatories, a lipid regulator
      agent, two angiotensin II antagonists, two antiepileptic drugs and a diuretic.
      Among personal care products, four preservatives and five UV filters were
      included. The method is based on solid-phase extraction (SPE) using Oasis HLB
      cartridges followed by ultra-high performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS). Up to three simultaneous transitions per compound
      were acquired to assure a reliable identification. A detailed study of the
      extraction process efficiency and matrix effects was carried out in surface water
      and effluent wastewater. The use of isotope-labeled internal standards (ILIS) was
      tested to compensate both potential SPE losses during sample extraction and
      signal suppression/enhancement observed, especially in EWW. Satisfactory
      correction in all water samples was only ensured when the own analyte ILIS was
      used. The use of analogues ILIS was a rather useful approach for correction in
      the majority of the samples tested when analyte ILIS was unavailable. The method
      was successfully validated in five different surface water (SW) samples and five
      effluent wastewater (EWW) samples spiked at two concentration levels (0.05 and
      0.5 MUg/L in SW; 0.1 and 0.5 MUg/L in EWW). The developed method was applied to
      the analysis of 22 samples (SW and EWW) from the Spanish Mediterranean area and
      51 reservoir water samples from Colombia. Personal care products were frequently
      detected, with the highest concentrations corresponding to benzophenone and
      benzophenone-4 (samples from Spain), and methylparaben (samples from Colombia).
      Several pharmaceuticals were detected in the Spanish samples, where irbesartan
      and valsartan - two Angiotensin II antagonists that are not commonly monitored in
      the aquatic environment - were the compounds most frequently detected.

PMID- 22967657
TI  - Voltammetric determination of beta-carotene in raw vegetables and berries in
      Triton X100 media.
AB  - Electrochemical behavior of beta-carotene in polar organic media and solubilized
      systems has been investigated. beta-Carotene is irreversibly oxidized at 500 and
      920 mV on glassy carbon electrode in 0.1 M LiClO(4) ethanol containing 10% of
      CH(2)Cl(2). Effect of surfactants (cationic, nonionic and anionic) on
      voltammetric characteristics of beta-carotene oxidation has been evaluated. High
      concentrations of surfactants facilitate the electrooxidation of beta-carotene
      independently of surfactant type. The increase of oxidation current by 7-11% has
      been obtained in the presence of nonionic surfactant. The best results have been
      observed in 10 mM Triton X100 media. The peak current showed a linear dependence
      with the beta-carotene concentration over the range 10-380 MUM. The calculated
      detection limit was 2.5 MUM and the quantification limit was 8.3 MUM. Liquid
      extraction of beta-carotene with dichloromethane from raw vegetables and berries
      has been developed. Quantitative determination of beta-carotene in real samples
      using cyclic voltammetry in Triton X100 media combined with preliminary
      extraction has been carried out. The results obtained are in good agreement with
      data of nutrient database for standard references.

PMID- 22967658
TI  - Wide-range quantification of human thyroid-stimulating hormone using gold
      nanopatterned single-molecule sandwich immunoassay chip.
AB  - We performed wide-range quantification of human thyroid-stimulating hormone
      (hTSH) using a gold nano-patterned sandwich immunoassay chip. Objective-type
      total internal reflection fluorescence microscopy (TIRFM) was used to detect hTSH
      at the single-molecule level. A gold spot with a diameter of 100 nm on a 10-mm
      square glass substrate was fabricated by electron beam nanolithography. When hTSH
      bound to antibodies conjugated to each 100-nm gold spot, there was an increase in
      the relative fluorescent intensity (RFI). The detection limit of this "TSH
      nanoarray chip" was 360 zM (equivalent to five molecules), which demonstrated
      that a TSH-nanoarray chip could be used for detection at the single-molecule
      level. A linear response was observed over a wide dynamic range (from 360 zM to
      36 pM, R=0.9812) without a fluorescence quenching effect. A significant
      enhancement in the sensitivity (~12,000-fold) was achieved with the 100-nm gold
      nano-patterned chip compared with results obtained using a traditional
      chemiluminescence immunoassay for the evaluation of TSH in human serum.

PMID- 22967659
TI  - Comparison of IRMS and NMR spectrometry for the determination of intramolecular
      13C isotope composition: application to ethanol.
AB  - Isotopic (13)C NMR is a relatively recent technique which allows the
      determination of intramolecular (13)C isotope composition at natural abundance.
      It has been used in various scientific fields such as authentication,
      counterfeiting or plant metabolism. Although its precision has already been
      evaluated, the determination of its trueness remains still challenging. To deal
      with that issue, a comparison with another normalized technique must be achieved.
      In this work, we compare the intramolecular (13)C isotope distribution of ethanol
      from different origins obtained using both Isotope Ratio Mass Spectrometry (IRMS)
      and Nuclear Magnetic Resonance (NMR) spectrometry techniques. The IRMS approach
      consists of the oxidation of ethanol to acetic acid followed by the degradation
      of the latter for the analysis of each fragments formed. We show here that the
      oxidation of ethanol to acetic acid does not bring any significant error on the
      determination of the site-specific delta(13)C (delta(13)C(i)) of ethanol using
      the IRMS approach. The difference between the data obtained for 16 samples from
      different origins using IRMS and NMR approaches is not statistically significant
      and remains below 0.30/00. These results are encouraging for the future studies
      using isotopic NMR, especially in combination with the IRMS approach.

PMID- 22967660
TI  - Automated on-line preconcentration of trace aqueous mercury with gold trap
      focusing for cold vapor atomic absorption spectrometry.
AB  - A fully automated system for the determination of trace mercury in water by cold
      vapor atomic absorption spectrometry (CVAAS) is reported. The system uses
      preconcentration on a novel sorbent followed by liberation of the mercury and
      focusing by a gold trap. Mercury ions were extracted from water samples by
      passage through a solid phase sorbent column containing 2-(3-(2
      aminoethylthio)propylthio)ethanamine modified silica gel. The captured mercury is
      released by thiourea and then elemental Hg is liberated by sodium borohydride.
      The vapor phase Hg is recaptured on a gold-plated tungsten filament. This is
      liberated as a sharp pulse (half-width<2 s) by directly electrically heating the
      tungsten filament in a dry argon stream. The mercury is measured by CVAAS; no
      moisture removal is needed. The effects of chloride and selected interfering ions
      were studied. The sample loading flow rate and argon flow rates for solution
      purging and filament sweeping were optimized. An overall 50-fold improvement in
      the limit of detection was observed relative to direct measurement by CVAAS. With
      a relatively modest multi-user instrument we attained a limit of detection of 35
      ng L(-1) with 12% RSD at 0.20 MUg L(-1) Hg level. The method was successfully
      applied to accurately determine sub-MUg L(-1) level Hg in standard reference
      water samples.

PMID- 22967661
TI  - Real-time and in-situ cell imaging of thiol compounds in living cells using
      maleimide BODIPY labeling.
AB  - In this paper, a simple analytical method for the visualization of thiol
      compounds including glutathione (GSH), N-acetylcysteine (NAC), cysteine (Cys) and
      coenzyme A (CoA) in living cells is developed based on 1,3,5,7-tetramethyl-8
      phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o-M) labeling. By using
      of this fluorogenic reagent, in-situ imaging of thiol compounds in cells could be
      achieved in only 90 s, which is much faster than that mentioned in other reports.
      The fluorescence of derivative products in living cells could be stable for
      atleast 15 min under irradiation, and can be quantified by HPLC easily in only 6
      min.

PMID- 22967663
TI  - The stable and water-soluble neodymium-doped lanthanide fluoride nanoparticles
      for near infrared probing of copper ion.
AB  - Neodymium (Nd(3+)) doped nanomaterials exhibited the unique near infrared (NIR)
      luminescence properties. However, the application of Nd-doped nanomaterials to
      chemosensors was rarely explored. Herein, the water-soluble 2-aminoethyl
      dihydrogen phosphate stabilized Nd-doped LaF(3) (ADP-Nd-LaF(3)) nanoparticles
      were explored as the NIR probe for chemosensors. The NIR emission intensity at
      1061 nm of ADP-Nd-LaF(3) nanoparticles kept stable in the aqueous solution of
      various pH and coexisting of most common metal ions except copper ion,
      consequently, the ADP-Nd-LaF(3) nanoparticles were developed as a high selective
      NIR probe for Cu(II). The NIR emission of ADP-Nd-LaF(3) exhibits a linear
      quenching response to Cu(II) in the range 5-100 MUM, with a detection limit of
      0.8 MUM. The precision of eleven replicate detections of 5 MUM Cu(II) was 0.5%
      (RSD). The recovery of spiked Cu(II) in human urine and waste water samples
      ranged from 102 to 109%. The possible mechanism of Cu(II)-induced fluorescence
      quenching of ADP-Nd-LaF(3) nanoparticles was also discussed.

PMID- 22967662
TI  - Chemiluminescence detection of amino acids and related compounds using acidic
      potassium permanganate, manganese(IV) or tris(2,2'-bipyridine)ruthenium(III).
AB  - We have explored the chemiluminescence response of amino acids and related
      compounds (including the tripeptide glutathione, and disulfides: cystine,
      homocystine and glutathione disulfide) with several new adaptations of the
      permanganate and tris(2,2'-bipyridine)ruthenium(III) ([Ru(bipy)(3)](3+)) reagents
      and a recently developed colloidal manganese(IV) system. The selectivity of the
      permanganate reagent can be directed towards tyrosine or thiol compounds like
      cysteine, homocysteine and glutathione by manipulating reaction conditions
      (providing limits of detection of 4 nM tyrosine and 5 nM glutathione). Colloidal
      Mn(IV) produced measureable responses with all analytes, but was most suitable
      for tryptophan, tyrosine, thiols and disulfides, including alpha-lipoic acid and
      dihydrolipoic acid, for which the limits of detection were 30 nM and 20 nM,
      respectively. A stabilised form of [Ru(bipy)(3)](3+), prepared by oxidising
      [Ru(bipy)(3)](ClO(4))(2) in acetonitrile, exhibited similar selectivity to that
      of the conventional aqueous reagent. The [Ru(bipy)(3)](3+) reagent was effective
      for the detection of secondary amino acids such as proline and hydroxyproline, as
      well as the disulfide, homocystine.

PMID- 22967664
TI  - Nonenzymatic electrochemical glucose sensor based on novel Pt-Pd nanoflakes.
AB  - The sluggish kinetic-controlled glucose oxidation reaction on Pt electrodes is
      well recognized as the most critical issue that blocks the development and
      commercialization of enzyme-free glucose sensors, and increasing attention is
      being focused on improving the analytical performances of these nonenzymatic
      sensors through exploring new Pt-based catalysts. In the present research, we
      synthesized novel Pt-Pd nanoflakes (Pt-Pd NFs) with three-dimensional
      architectures on a homemade screen-printed gold film electrode (SPGFE) substrate
      using a facile electrochemical deposition without any template, and further
      investigated the properties of the as-fabricated Pt-Pd NFs/SPGFE for enzymeless
      glucose detection. The results reveal that the proposed Pt-Pd nanostructure can
      provide preeminent electrocatalytic activity and excellent selectivity for enzyme
      free glucose sensing under simulative physiological conditions, mainly
      attributing to its attractive structure, large active surface and appropriate
      applied potential. The resulting Pt-Pd NFs/SPGFE offers linear current responses
      for glucose with the concentration upper limit to 16 mM. The obtained sensitivity
      is calculated to be as high as 48.0 MUA cm(-2) mM(-1) in the presence of 0.15 M
      chlorides ions, and practical applications for blood sample analysis are also
      demonstrated. The proposed Pt-Pd structure is considered as a great potential
      building block for the fabrication of nonenzymatic electrochemical glucose
      sensors.

PMID- 22967665
TI  - The rate of melanoma transection with various biopsy techniques and the influence
      of tumor transection on patient survival.
AB  - BACKGROUND: Depth of melanoma invasion is critical because it dictates patient
      treatment and prognosis. Recent reports indicate melanoma transection with
      initial biopsy does not impact patient survival; however, tumor transection can
      lead to misdiagnosis and inaccurate staging. OBJECTIVE: This study assessed the
      rate of melanoma transection with various biopsy techniques and the impact of
      tumor transection on patient survival. METHODS: We conducted a retrospective
      review of all melanoma cases at our institution between 2000 and 2008. Of the 490
      melanoma cases identified, 479 met inclusion criteria for the study. The
      transection rates of biopsy techniques were determined. Cases of transected
      tumors were matched with nontransected cases in a retrospective case-control
      fashion to evaluate survival. RESULTS: The rate of melanoma transection was 1.5%
      for excisional biopsies, 4.1% for punch biopsies, and 9.0% for saucerization
      biopsies. The means of disease-free survival for the control and transected
      groups were 911 days and 832.7 days, respectively (P value .67). Overall survival
      for the control group was 1073.7 days versus 1012.4 days for the transected group
      (P value .72). LIMITATIONS: The study used a select population. The sample size
      of transected biopsies was limited, in turn limiting the power of the study.
      Residents performed the majority of biopsies. CONCLUSION: Punch and saucerization
      biopsies were more likely to transect tumors than excisional biopsies. The
      transection of melanoma did not affect overall disease-free survival or mortality
      in the population studied.

PMID- 22967666
TI  - Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia
      (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Methyl helicterate is a triterpenoid isolated
      from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional
      Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively
      proved. AIM OF THE STUDY: The purpose of this study was to investigate the effect
      of methyl helicterate (MH) on liver fibrosis in rats induced by carbon
      tetrachloride (CCl(4)) and to explore its underlying mechanism. MATERIALS AND
      METHODS: Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by
      intragastric administration with 2 ml/kg CCl(4) (mixed 1:1 in peanut oil) twice a
      week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90 mg/kg) on
      hepatic fibrosis, liver function, histological study and hepatic fibrosis
      evaluation were performed. Liver function was assessed by determining the serum
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb)
      and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic
      acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the
      evaluation of hepatic fibrosis. The underlying mechanism was investigated by
      measuring oxidative stress level and detecting the expression of TGF-beta1 mRNA
      and Smad3 protein. RESULTS: MH (33.45, 66.90 mg/kg) treatment significantly
      inhibited the loss of body weight and the increase of liver index in rats induced
      by CCl(4). MH also improved the liver function as indicated by decreasing serum
      enzymatic activities of ALT, AST, TP and Alb (P<0.05). Histological results
      indicated that MH alleviated liver damage and reduced the formation of fibrous
      septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05).
      Research on mechanism showed that MH could markedly reduce liver malondialdehyde
      (MDA) concentration, increase activities of liver superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-beta1 mRNA and
      Smad3 protein (P<0.05). CONCLUSIONS: Our findings indicated that MH can inhibit
      CCl(4)-induced hepatic fibrosis, which may be ascribed to its radical scavenging
      action, antioxidant activity, and modulation of TGF-beta-Smad3 signaling pathway.

PMID- 22967667
TI  - Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in
      hyperuricemic mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ramulus Mori, the branch of Morus alba, is widely
      used in traditional Chinese medicine prescriptions to treat gout and
      hyperuricemia. AIM OF THIS STUDY: To evaluate the uricosuric and nephroprotective
      effects of ethanol extract of Ramulus Mori (ERM) and explore its possible
      mechanisms in hyperuricemic mice. MATERIALS AND METHODS: HPLC analysis was
      employed to determine the main constituents. Hyperuricemia was induced by
      potassium oxonate (250 mg/kg) in male mice. ERM (10, 20 and 40 mg/kg) was orally
      administered to hyperuricemic and normal mice for 7 days. Serum and urine levels
      of uric acid, creatinine and blood urea nitrogen (BUN) were measured.
      Simultaneously, renal mRNA and protein levels of mouse urate transporter 1
      (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and
      organic cation/carnitine transporters (mOCT1/2, mOCTN1/2) were analyzed by RT-PCR
      and Western blotting methods. RESULTS: ERM mainly contained mulberroside A,
      oxyresveratrol, 4-hydroxycinnamic acid, resveratrol, 7-hydroxycumarin and morin.
      ERM significantly reduced serum urate levels and increased 24h-urine urate
      excretion and fractional excretion of uric acid in hyperuricemic mice. It
      effectively restored oxonate-induced expression alteration of renal mURAT1,
      mGLUT9 and mOAT1, resulting in urate excretion enhancement. Moreover, ERM
      decreased serum creatinine and BUN levels and increased creatinine clearance, and
      up-regulated expression of mOCT1/2 and mOCTN1/2, contributing to kidney function
      improvement in this model. CONCLUSION: These results suggest that ERM exerts the
      uricosuric and nephroprotective actions by the regulation of these renal organic
      ion transporters in hyperuricemic mice, and provide scientific support for the
      empirical use of Ramulus Mori.

PMID- 22967670
TI  - Abstracts of the Australian Gastroenterology Week 2012. October 16-19, 2012.
      Adelaide, South Australia, Australia.

PMID- 22967668
TI  - Genomic structure, organization and localization of the acetylcholinesterase
      locus of the olive fruit fly, Bactrocera oleae.
AB  - Acetylcholinesterase (AChE), encoded by the ace gene, is a key enzyme of
      cholinergic neurotransmission. Insensitive acetylcholinesterase (AChE) has been
      shown to be responsible for resistance to OPs and CBs in a number of arthropod
      species, including the most important pest of olives trees, the olive fruit fly
      Bactrocera oleae. In this paper, the organization of the B. oleae ace locus, as
      well as the structural and functional features of the enzyme, are determined. The
      organization of the gene was deduced by comparison to the ace cDNA sequence of B.
      oleae and the organization of the locus in Drosophila melanogaster. A similar
      structure between insect ace gene has been found, with conserved exon-intron
      positions and junction sequences. The B. oleae ace locus extends for at least 75
      kb, consists of ten exons with nine introns and is mapped to division 34 of the
      chromosome arm IIL. Moreover, according to bioinformatic analysis, the Bo AChE
      exhibits all the common features of the insect AChE. Such structural and
      functional similarity among closely related AChE enzymes may implicate
      similarities in insecticide resistance mechanisms.

PMID- 22967671
TI  - Intracellular zinc is required for intestinal cell survival signals triggered by
      the inflammatory cytokine TNFalpha.
AB  - The essential micronutrient zinc has long been known to be a functional component
      of diverse structural proteins and enzymes. More recently, important roles for
      free or loosely bound intracellular zinc as a signaling factor have been
      reported. Insufficient zinc intake was shown to exacerbate symptoms in mouse
      models of inflammation such as experimental colitis, while zinc supplementation
      was found to improve intestinal barrier function. Herein, we provide evidence
      that intracellular zinc is essential for maintaining intestinal epithelial
      integrity when cells are exposed to the inflammatory cytokine Tumor Necrosis
      Factor (TNF)alpha. Using the human intestinal Caco-2/TC7 cell line as an in vitro
      model, we demonstrate that depletion of intracellular zinc affects TNFalpha
      triggered signaling by shifting intestinal cell fate from survival to death. The
      mechanism underlying this effect was investigated. We show that TNFalpha promotes
      a zinc-dependent survival pathway that includes modulation of gene expression of
      transcription factors and signaling proteins. We have identified multiple
      regulatory steps regulated by zinc availability which include the induction of
      cellular Inhibitor of APoptosis (cIAP2) mRNA, possibly through activation of
      Nuclear Factor-Kappa B (NF-kappaB), as both nuclear translocation of the p65
      subunit of NF-kappaB and up-regulation of cIAP2 mRNA were impaired following zinc
      depletion. Moreover, X-linked inhibitor of apoptosis protein level was profoundly
      reduced by zinc depletion. Our results provide a possible molecular explanation
      for the clinical observation that zinc supplements ameliorate Crohn's disease
      symptoms and decrease intestinal permeability in experimental colitis.

PMID- 22967672
TI  - The C-terminal domain of the heavy chain of tetanus toxin given by intramuscular
      injection causes neuroprotection and improves the motor behavior in rats treated
      with 6-hydroxydopamine.
AB  - We have previously shown that the intrastriatal injection of the C-terminal
      domain of tetanus toxin (Hc-TeTx) protects the nigrostriatal-dopaminergic
      pathways and improves motor behavior in hemiparkinsonism-rat models caused by
      MPP(+) (1-methyl-4-phenylpyridinium). Here we have investigated the protective
      effects of the intramuscular application of the Hc-TeTx on motor asymmetry and
      neurodegeneration in the striatum of 6-hydroxydopamine (6-OHDA)-treated rats.
      Adult male rats were intramuscularly injected with the recombinant Hc-TeTx
      protein (0.1-20MUg/kg, daily) 3days before the stereotaxic injection of 6-OHDA
      into the left striatum. Our results showed that the motor-improvement functions
      were extended for 4weeks in all Hc-TeTx-treated groups, obtaining the maximum
      performance with the highest dose of Hc-TeTx (20MUg/kg). The improvements found
      were 97%, 87%, and 70% in the turning behavior, stepping test, and cylinder test,
      respectively. The striatal levels of dopamine and its metabolites did not vary
      compared to the control group. Moreover, the peripheral treatment with Hc-TeTx in
      rats prevents, for 30days, the neurodegeneration in the striatum caused by the
      toxicity of the 6-OHDA. Our results lead us to believe that the Hc-TeTx could be
      a potential therapeutic agent in pathologies caused by impairment of dopaminergic
      innervations such as Parkinson's disease.

PMID- 22967673
TI  - Targeted delivery of therapeutics to bone and connective tissues.

PMID- 22967674
TI  - Augmented visual feedback of movement performance to enhance walking recovery
      after stroke: study protocol for a pilot randomised controlled trial.
AB  - BACKGROUND: Increasing evidence suggests that use of augmented visual feedback
      could be a useful approach to stroke rehabilitation. In current clinical
      practice, visual feedback of movement performance is often limited to the use of
      mirrors or video. However, neither approach is optimal since cognitive and self
      image issues can distract or distress patients and their movement can be obscured
      by clothing or limited viewpoints. Three-dimensional motion capture has the
      potential to provide accurate kinematic data required for objective assessment
      and feedback in the clinical environment. However, such data are currently
      presented in numerical or graphical format, which is often impractical in a
      clinical setting. Our hypothesis is that presenting this kinematic data using
      bespoke visualisation software, which is tailored for gait rehabilitation after
      stroke, will provide a means whereby feedback of movement performance can be
      communicated in a more meaningful way to patients. This will result in increased
      patient understanding of their rehabilitation and will enable progress to be
      tracked in a more accessible way. METHODS: The hypothesis will be assessed using
      an exploratory (phase II) randomised controlled trial. Stroke survivors eligible
      for this trial will be in the subacute stage of stroke and have impaired walking
      ability (Functional Ambulation Classification of 1 or more). Participants (n =
      45) will be randomised into three groups to compare the use of the visualisation
      software during overground physical therapy gait training against an intensity
      matched and attention-matched placebo group and a usual care control group. The
      primary outcome measure will be walking speed. Secondary measures will be
      Functional Ambulation Category, Timed Up and Go, Rivermead Visual Gait
      Assessment, Stroke Impact Scale-16 and spatiotemporal parameters associated with
      walking. Additional qualitative measures will be used to assess the participant's
      experience of the visual feedback provided in the study. DISCUSSION: Results from
      the trial will explore whether the early provision of visual feedback of
      biomechanical movement performance during gait rehabilitation demonstrates
      improved mobility outcomes after stroke and increased patient understanding of
      their rehabilitation. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN79005974.

PMID- 22967675
TI  - Performance characteristics of monoclonal antibodies as recyclable binders to
      cardiac troponin I.
AB  - Acute myocardial infarction is a typical disorder that requires continuous
      monitoring for early detection of potential life-threatening situations. To this
      end, we used different methods to screen for rapidly reversible antibodies, among
      22 hybridoma clones, against cardiac troponin I (cTnI), which is a specific
      marker indicating the disease. The dissociation rates of antibodies were
      underestimated by up to a factor of 1000 because of bivalent binding when tested
      with the antigen immobilized on solid surfaces. This effect was also observed in
      a sandwich immunoassay, in which the detection antibody cross-linked with various
      antigen molecules already bound to the capture antibody. Although multiple
      binding events contributed to enhanced detection capability, it was difficult to
      recycle the immunosensor. We then devised a screening system by arranging the
      test antibody for the capture binder immobilized on a label-free sensor. This
      enabled us to select fast reactive antibodies of which one (clone 24) was shown
      to be recyclable, even in serum-containing medium. Using this antibody,
      repetitive detection of cTnI with a rapid response time (half-life of
      dissociation: about 4min on average) and high detection capability (0.1ng/ml) was
      achieved, which is very important for detection in a clinical setting.

PMID- 22967676
TI  - An early venous abnormality: a potential cause of arteriovenous malformation
      recurrence.
AB  - In adults, complete surgical resection of arteriovenous malformations (AVMs) is
      generally curative. Recurrence of AVMs is extremely rare and most often delayed
      over many years. The authors report the case of a man in his 20s with rapid AVM
      recurrence and dual blood supply from the dura and intracerebral vessels. Early
      recurrence of the AVM allowed documentation of the early events associated with
      this recurrence. This was evidenced by the first appearance of an early vein
      without any signs of abnormal vasculature, suggesting that abnormality of the
      venous drainage system might be an inciting event in the recurrence and perhaps
      genesis of AVMs.

PMID- 22967677
TI  - A new treatment protocol using photobiomodulation and muscle/bone/joint recovery
      techniques having a dramatic effect on a stroke patient's recovery: a new weapon
      for clinicians.
AB  - The subject of this case study is a 29-year-old woman who suffered a brainstem
      stroke. She remained severely dizzy, had a non-functional left hand secondary to
      weakness, severe spasticity in the right hand, a right lateral sixth nerve palsy
      and was unable to ambulate on presentation. The stroke occurred 2 years before
      presentation. The subject had been treated for 21 months at two different stroke
      rehabilitation centres before presentation. Our stroke protocol includes
      photobiomodulation administered with the XR3T-1 device and
      'muscle/bone/joint/soft tissue' recovery techniques. The patient was seen once a
      week for 8 weeks and treatment sessions lasted approximately 60 min. The results
      were dramatic: after 8 weeks of implementation of our protocol, the patient
      demonstrated positive change in every area of her deficits as determined by
      improvements in physical examination findings. The gains achieved at 8 weeks have
      been maintained to this day and she continues to be treated once every 4 weeks.

PMID- 22967678
TI  - Molar pregnancy in postmenopausal women: a rare phenomenon.
AB  - Benign gestational trophoblastic disease generally occurs in women of the
      reproductive age group and is extremely rare in postmenopausal women. We describe
      a case of complete hydatidiform mole in a 60-year-old postmenopausal woman who
      was referred with diagnosis of suspected malignancy/myoma resulting in delay in
      management. This case highlights the fact that gestational trophoblastic disease
      can occur in menopausal woman and this should be included in the differential
      diagnosis of perimenopausal and postmenopausal haemorrhage to prevent delay in
      diagnosis and treatment.

PMID- 22967679
TI  - Tension pneumothorax at anaesthetic induction in an ex-premature infant with
      bronchopulmonary dysplasia.
AB  - ME, a 12-week-old premature infant with a history of complicated ventilatory
      support at birth, was referred to as a large tertiary centre for urgent retinal
      laser photocoagulation for retinopathy of prematurity. Following routine
      induction by a consultant paediatric anaesthetist, immediate ventilation
      difficulties were encountered, associated with a distended abdomen. Rapid
      assessment and escalation of the situation occurred, including assistance from
      several consultants. ME was diagnosed as having a pneumothorax. Rapid
      intervention, including needle decompression and insertion of a chest drain
      stabilised the patient. The procedure was cancelled, and the patient returned to
      intensive care. Over the next few days the patient gradually improved, and was
      gradually stepped down. The patient continued to improve, successfully overcoming
      the pneumothorax, pneumonia and insertion of a ventriculoperitoneal shunt, and
      eventually was discharged back to the referring hospital.

PMID- 22967680
TI  - An unusual presentation of an epidermoid brain tumour: a tale of two specialties.
AB  - A 33-year-old right-handed lady was referred to the psychiatry and neurology
      services by her general practitioner. Previously, she was under psychiatric care
      for bipolar affective disorder. Recently, her mood had deteriorated prompting the
      re-referral to the psychiatrists. In addition she had strange attacks. These
      strange attacks seemed to her like 'sensory overload' or that the 'brain just
      stops'. Other sensations throughout the attacks included feeling like she is in a
      'fish bowl' and surrounding sights and sounds were distorted. She could not
      speak. After the attack she was hot and flustered, suffered memory loss and was
      tearful. Both the psychiatrist and the neurologist considered the possibility of
      these attacks being psychiatric in aetiology. However, the alternative
      possibility of a coexistence to epilepsy and depression was investigated and MRI
      demonstrated an epidermoid tumour with the supratentorial portion displacing the
      left temporal lobe.

PMID- 22967681
TI  - Three-dimensional spectral domain optical coherence tomography of retina in
      choroidal metastasis due to uterine endometrial carcinoma.
AB  - Spectral domain optical coherence tomography (SD-OCT) three-dimensional (3D)
      imaging in choroidal metastasis, due to uterine endometrial carcinoma, is
      reported for the first time. SD-OCT revealed a dome-shaped elevation of the
      retina. Neurosensory detachment with splitting of the retinal layers, at some
      places, was observed. 3D SD-OCT allows evaluation of secondary retinal pigment
      epithelial and intraretinal changes due to metastatic choroidal lesion.

PMID- 22967682
TI  - Dyke-Davidoff-Masson syndrome-like picture in a case of Takayasu arteritis: an
      enigma.
AB  - Authors describe the case of a 16-year-old girl who presented with fever, tonic
      clonic seizures, unequal arm blood pressures and pulselessness in the left upper
      limb. On examination, there was a systolic bruit over umbilical region, a
      pansystolic murmur of mitral regurgitation was found. Neurological examination
      was normal except for an asymmetry in brain hemicircumference one side compared
      with the other. She has borderline intelligence (IQ 70) according to Wechsler
      Adult Performance Intelligence Scale. Magnetic resonance imaging (MRI) of brain
      revealed atrophic of left cerebral hemisphere with mildly ventricular dilatation,
      prominent paranasal and mastoid air cells, suggestive of Dyke-Davidoff-Masson
      syndrome (DDMS). Conventional angiography showed narrowed left internal carotid
      artery. There was also stenosed brachial artery, absent left renal artery with
      narrowed infrarenal abdominal aorta. The patient was put on antihypertensive
      drugs. We hypothesise that Takayasu arteritis and related vascular occlusion is
      the cause of her acquired cerebral changes.

PMID- 22967683
TI  - Vein of Galen malformation.

PMID- 22967684
TI  - Well recognised but still overlooked: norepinephrine extravasation.

PMID- 22967685
TI  - Bilateral hypogeusia caused by a small lesion in the lower midbrain tegmentum.
AB  - We report a case with multiple sclerosis which showed bilateral hypogeusia due to
      a small lesion in the lower midbrain tegmentum. Sweet taste was diminished only
      on the contralateral side in the territory of the chorda tympani, and salty, sour
      and bitter tastes were diminished bilaterally. All taste modalities were
      preserved in the territory of the greater petrosal nerve. The findings in our
      patient and in the literature suggest that the second gustatory fibres
      ipsilaterally ascend from the nucleus of the solitary tract to the midbrain and
      partially cross at the inferior border of the midbrain. The features of
      hypogeusia in our case suggest segregated channels in the gustatory pathway
      conveying taste perception of distinct taste modalities and from distinct
      innervation territories.

PMID- 22967686
TI  - Bochdalek hernia in pregnancy.
AB  - Asymptomatic diaphragmatic hernias in reproductive-aged women are rare but pose
      significant morbidity for pregnancy. This is a case of a woman at 29 weeks'
      gestation with abdominal pain and shortness of breath. Five years prior she had
      been incidentally diagnosed with a small congenital diaphragmatic hernia of
      Bochdalek. Following preconception care, she opted against repair of the hernia
      prior to pregnancy due to lack of symptoms and no clear recommendation for repair
      from the surgeon. Imaging studies on emergency room presentation demonstrated a
      large herniation of viscera into her chest occupying her entire left chest with
      slight cardiac displacement. Through a multidisciplinary approach, she was
      stabilised and eventually delivered at 31 weeks due to worsening pulmonary
      function. The hernia was repaired postpartum. We recommend repair of any
      diaphragmatic hernia prior to conception to prevent significant maternal and
      fetal morbidity or mortality. A multidisciplinary approach allows for planning.

PMID- 22967687
TI  - Under pressure: an ocular complication of oral corticosteroid therapy.
AB  - We describe the case of a patient with steroid sensitive nephrotic syndrome who
      is admitted with headaches, eye pain and reduced visual acuity. Despite thorough
      investigation no cause for the pain is identified. On a subsequent admission for
      recurrence of her symptoms her intraocular pressures are measured, which are
      markedly raised. Immediate medical treatment, as well as prompt weaning of her
      steroid therapy avoided the need for trabeculectomy surgery. We review this case
      and the literature surrounding this condition in children.

PMID- 22967688
TI  - Caustic skin burn caused by sodium hydroxide.

PMID- 22967689
TI  - Spontaneous intraperitoneal haemorrhage during pregnancy.
AB  - This is a case report of spontaneous haemoperitoneum caused by ruptured utero
      ovarian vessels during the third trimester of pregnancy. The patient presented
      with acute abdominal pain and hypotension twice to the emergency room. The
      initial diagnosis was placental abruptio and the patient had emergency caesarean
      section. There was utero-ovarian plexus laceration and suture-ligation was
      performed. The maternal outcome was good. The infant had birth asphyxia and was
      extubated on the third day. Both mother and infant were discharged in good
      condition.

PMID- 22967690
TI  - Two supratentorial meningiomas: are they different?

PMID- 22967692
TI  - Sepsis update: management of severe sepsis and septic shock in the emergency
      department after the withdrawal of Xigris.

PMID- 22967691
TI  - Paediatric palliative home care in areas of Germany with low population density
      and long distances: a questionnaire survey with general paediatricians.
AB  - BACKGROUND: In 2007, the patient's right to specialised palliative home care
      became law in Germany. However, childhood palliative care in territorial states
      with low patient numbers and long distances requires adapted models to ensure an
      area-wide maintenance. Actually, general paediatricians are the basic care
      providers for children and adolescents. They also provide home care. The aim of
      this study was to improve the knowledge about general paediatrician's involvement
      in and contribution to palliative care in children. FINDINGS: To evaluate the
      current status of palliative home care provided by general paediatricians and
      their cooperation with other paediatric palliative care providers, a
      questionnaire survey was disseminated to general paediatricians in Lower Saxony,
      a German federal state with nearly eight million inhabitants and a predominantly
      rural infrastructure. Data analysis was descriptive.One hundred forty one of 157
      included general paediatricians completed the questionnaire (response rate:
      89.8%). A total of 792 children and adolescents suffering from life-limiting
      conditions were cared for by these general paediatricians in 2008. Severe
      cerebral palsy was the most prevalent diagnosis. Eighty-nine per cent of the
      general paediatricians stated that they had professional experience with
      paediatric palliative care.Collaboration of general paediatricians and other
      palliative care providers was stated as not well developed. The support by a
      specialised team including 24-hour on-call duty and the intensification of
      educational programs were emphasised. CONCLUSIONS: The current regional
      infrastructure of palliative home care in Lower Saxony can benefit from the
      establishment of a coordinated network of palliative home care providers.

PMID- 22967694
TI  - Adrenal inhibition following a single dose of etomidate in intubated traumatic
      brain injury victims.
AB  - BACKGROUND: Etomidate is frequently used to intubate traumatic brain injury (TBI)
      victims, even though it has been linked to adrenal insufficiency (AI) in some
      populations. Few studies have explored the risk of prolonged etomidate-induced AI
      among TBI victims. OBJECTIVE: To determine the risk and the length of AI induced
      by etomidate in patients intubated for moderate and severe TBI. METHODS:
      Participants in this observational study were moderate to severe intubated TBI
      victims aged >= 16 years. The anesthetic used (etomidate versus others) was
      determined solely by the treating emergency physician. Adrenocorticotropic
      hormone (ACTH) stimulation tests (250 MUg) were performed 24, 48, and 168 hours
      after intubation. AI was defined as an increase in serum cortisol 1 hour post
      ACTH test (delta cortisol) of less than 248.4 nmol/L. RESULTS: Forty subjects
      (participation 42.6%) underwent ACTH testing. Fifteen received etomidate, and 25
      received another anesthetic. There were no statistically significant differences
      between groups as to the cumulative incidence of AI at any measurement time.
      However, at 24 hours, exploratory post hoc analyses showed a significant decrease
      in delta cortisol (adjusted means: etomidate group: 305.1 nmol/L, 95% CI 214.7
      384.8 versus other anesthetics: 500.5 nmol/L, 95% CI 441.8-565.7). This decrease
      was not present at 48 and 168 hours. CONCLUSION: In TBI victims, although a
      single dose of etomidate does not increase the cumulative incidence of AI as
      defined, it seems to decrease the adrenal response to an ACTH test for 24 hours.
      The clinical impacts of this finding remain to be determined.

PMID- 22967695
TI  - The safety of ethanol infusions for the treatment of methanol or ethylene glycol
      intoxication: an observational study.
AB  - BACKGROUND: Methanol or ethylene glycol ingestion may result in significant
      morbidity or death without prompt treatment. Despite traditional and widespread
      use of intravenous ethanol as an antidote, its safety is not well described. An
      evaluation of the safety and ease of titrating ethanol infusions is necessary
      given the availability of an alternative antidote. OBJECTIVE: To evaluate the
      safety and ease of titrating ethanol infusions for the treatment of methanol or
      ethylene glycol ingestion. METHODS: We reviewed the hospital records of adults
      treated with ethanol at The Ottawa Hospital for methanol or ethylene glycol
      ingestion over a 9-year period. Using a standardized case report form, a single
      reviewer identified prespecified adverse events that developed after the start of
      ethanol therapy and classified dose adjustments during ethanol therapy as
      appropriate or inappropriate based on a priori criteria. RESULTS: Forty-nine
      cases of methanol or ethylene glycol ingestion treated with ethanol were included
      in the analysis, of which 45 underwent hemodialysis, 38 were admitted to the
      intensive care unit, and 4 died. At least one adverse event was identified in 45
      (92%) cases, including 35 (71%) with agitation requiring chemical or physical
      restraints and 10 (20%) with a depressed level of consciousness treated with
      intubation. The median number of ethanol concentration measurements per treatment
      course was 6 (range 0-24), of which only 27% were within the target range of 22
      to 30 mmol/L and 47% were below. When measured concentrations were outside the
      target, the adjustment in ethanol dosing (or lack thereof) was deemed
      inappropriate 59% of the time, including 69% of the time during hemodialysis.
      CONCLUSION: Based on actual practice in a large academic centre, adverse events
      occur frequently with intravenous ethanol infusions, and ethanol titration is
      inefficient. The safety profile and therapeutic drug monitoring considerations
      for ethanol should be considered when choosing an antidote for methanol or
      ethylene glycol ingestion.

PMID- 22967696
TI  - Impaired driving charges in injured impaired drivers requiring treatment in an
      emergency department.
AB  - OBJECTIVE: To determine the percentage of injured impaired drivers brought to the
      only trauma centre in Nova Scotia who were charged with impaired driving.
      METHODS: This retrospective observational study identified alcohol impaired
      drivers involved in a motor vehicle crash (MVC) brought to the emergency
      department (ED). Patients were selected based on blood alcohol concentrations
      (BACs) found to be above the legal limit. Medical records were examined to
      determine if the patient was the driver in an MVC. Patient records were then
      cross-referenced with a police database to determine the percentage of injured
      impaired drivers who were charged with impaired driving. RESULTS: Between April
      1, 2006, and April 1, 2008, 1,102 patients brought to the QEII Health Sciences
      Centre (QEII HSC) ED were found to have BACs over the legal limit. Of these
      patients, only 57 (5.2%) were found to have been the driver in an MVC. The
      majority of patients were male (49; 86%), with an average age of 32 years. Most
      injuries (51; 89.5%) were the result of a single-vehicle crash. The mean Glasgow
      Coma Scale score was 12.6, and the mean Injury Severity Score was 14.4. Cross
      referencing with police records showed that only 22.8% (13 of 57) of injured
      drivers were charged with impaired driving. Those drivers not charged with
      impaired driving had a significantly lower median BAC and median age. CONCLUSION:
      During the study, the majority of alcohol-impaired drivers injured in an MVC who
      were brought to the QEII HSC ED for assessment of their injuries were not charged
      with impaired driving.

PMID- 22967698
TI  - Frequent users of an inner-city emergency department.
AB  - BACKGROUND: Within the emergency department (ED) patient population there is a
      subset of patients who make frequent visits. This chart review sought to
      characterize this population and identify strategies to reduce frequent ED
      visits. METHODS: Frequent use at an urban tertiary care centre was defined as 15
      or more visits over 1 year. The details of each visit-demographics, entrance
      complaint, discharge diagnosis, arrival method, Canadian Triage and Acuity Scale
      (CTAS) score, and length of stay-were analyzed and compared to data from the
      entire ED population for the same period. RESULTS: Ninety-two patients generated
      2,390 ED visits (of 25,523 patients and 44,204 visits). This population was
      predominantly male (66%) and middle-aged (median 42 years), with no fixed address
      (27.2%). Patients arrived by ambulance in 59.3% of visits with less acute CTAS
      scores than the general population. Substance use accounted for 26.9% of entrance
      complaints. Increased lengths of stay were associated with female gender and
      abnormal vital signs, whereas shorter stays were associated with no fixed address
      and substance use (. < 0.05). Admissions were lower than the general population,
      and women were twice as likely as men to be admitted (. < 0.05). Patients left
      without being seen in 15.8% of visits. CONCLUSIONS: High-frequency ED users are
      more likely to be male, younger, and marginally housed and to present secondary
      to substance use. Although admissions among this population are low, the costs
      associated with these presentations are high. Interventions designed to decrease
      visits and improve the health of this population appear warranted.

PMID- 22967697
TI  - Antibiotic resistance in isolates recovered from women with community-acquired
      urinary tract infections presenting to a tertiary care emergency department.
AB  - INTRODUCTION: We sought to determine the antibiotic susceptibility of organisms
      causing community-acquired urinary tract infections (UTIs) in adult females
      attending an urban emergency department (ED) and to identify risk factors for
      antibiotic resistance. METHODS: We reviewed the ED charts of all nonpregnant,
      nonlactating adult females with positive urine cultures for 2008 and recorded
      demographics, diagnosis, complicating factors, organism susceptibility, and risk
      factors for antibiotic resistance. Odds ratios (ORs) and 95% confidence intervals
      (CIs) for potential risk factors were calculated. RESULTS: Our final sample
      comprised 327 UTIs: 218 were cystitis, of which 22 were complicated cases and 109
      were pyelonephritis, including 22 complicated cases. Escherichia coli accounted
      for 82.3% of all UTIs, whereas Staphylococcus saprophyticus accounted for 5.2%.
      In uncomplicated cystitis, 9.5% of all isolates were resistant to ciprofloxacin
      and 24.0% to trimethoprim-sulfamethoxazole (TMP-SMX). In uncomplicated
      pyelonephritis, 19.5% of isolates were resistant to ciprofloxacin and 36.8% to
      TMP-SMX. In UTI (all types combined), any antibiotic use within the previous 3
      months was a significant risk factor for resistance to both ciprofloxacin (OR
      3.34, 95% CI 1.16-9.62) and TMP-SMX (OR 4.02, 95% CI 1.48-10.92). Being 65 years
      of age or older and having had a history of UTI in the previous year were risk
      factors only for ciprofloxacin resistance. CONCLUSIONS: E. coli was the
      predominant urinary pathogen in this series. Resistance to ciprofloxacin and TMP
      SMX was high, highlighting the importance of relevant, local antibiograms. Any
      recent antibiotic use was a risk factor for both ciprofloxacin and TMP-SMX
      resistance in UTI. Our findings should be confirmed with a larger prospective
      study.

PMID- 22967700
TI  - A telltale heart: an unusual chest radiograph in a trauma patient. Cardiac
      torsion.

PMID- 22967701
TI  - Locked-in syndrome: a critical and time-dependent diagnosis.
AB  - Locked-in syndrome (LIS) is the combination of quadriplegia and anarthria
      (inability to speak), with the preservation of consciousness. The majority of
      cases are caused by basilar artery occlusion leading to brainstem infarction in
      the ventral pons, yet numerous other etiologies have been described. The
      diagnosis of LIS is completely dependent on the physician's ability to know that
      these manifestations originate in the brainstem and the posterior circulation
      that supplies it. This knowledge hinges on the ability of the examining physician
      to conduct a rapid, yet appropriately thorough neurologic examination. With
      recent advances in interventional neuroradiology leading to improved patient
      outcomes, LIS has evolved into a critical, time-dependent diagnosis. Herein, we
      present the case of a male patient who initially presented to the emergency
      department of a community hospital with coma of unknown cause. By presenting this
      case and focusing on the importance of the occulomotor exam, we hope to help in
      the rapid identification and treatment of patients with LIS in the emergency room
      and avoid outcomes similar to that of our patient.

PMID- 22967702
TI  - Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult
      bilateral peripheral facial nerve palsy due to Lyme disease.
AB  - Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem
      disorder characterized by three clinical stages: dermatologic, neurologic, and
      rheumatologic. The number of known Lyme disease-endemic areas in Canada is
      increasing as the range of the vector Ixodes scapularis expands into the eastern
      and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New
      Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in
      Canada. The use of field surveillance to map risk and endemic regions suggests
      that these geographic areas are growing, in part due to the effects of climate
      warming. Peripheral facial nerve palsy is the most common neurologic abnormality
      in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic
      peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a
      case of occult bilateral facial nerve palsy due to Lyme disease initially
      diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients
      presenting with unilateral or bilateral peripheral facial nerve palsy should be
      evaluated for Lyme disease with serologic testing to avoid misdiagnosis.
      Serologic testing should not delay initiation of appropriate treatment for
      presumed Bell palsy.

PMID- 22967704
TI  - DNA methylation inhibitors in cancer: recent and future approaches.
AB  - This review presents the different human DNA methyltransferases (DNMTs), their
      biological roles, their mechanisms of action and their role in cancer. The
      description of assays for detecting DNMT inhibitors (DNMTi) follows. The
      different known DNMTi are reported along with their advantages, drawbacks and
      clinical trials. A discussion on the features of the future DNMT inhibitors will
      conclude this review.

PMID- 22967703
TI  - An integrated approach to identify causal network modules of complex diseases
      with application to colorectal cancer.
AB  - BACKGROUND: Many methods have been developed to identify disease genes and
      further module biomarkers of complex diseases based on gene expression data. It
      is generally difficult to distinguish whether the variations in gene expression
      are causative or merely the effect of a disease. The limitation of relying on
      gene expression data alone highlights the need to develop new approaches that can
      explore various data to reflect the casual relationship between network modules
      and disease traits. METHODS: In this work, we developed a novel network-based
      approach to identify putative causal module biomarkers of complex diseases by
      integrating heterogeneous information, for example, epigenomic data, gene
      expression data, and protein-protein interaction network. We first formulated the
      identification of modules as a mathematical programming problem, which can be
      solved efficiently and effectively in an accurate manner. Then, we applied our
      approach to colorectal cancer (CRC) and identified several network modules that
      can serve as potential module biomarkers for characterizing CRC. Further
      validations using three additional gene expression datasets verified their
      candidate biomarker properties and the effectiveness of the method. Functional
      enrichment analysis also revealed that the identified modules are strongly
      related to hallmarks of cancer, and the enriched functions, such as inflammatory
      response, receptor and signaling pathways, are specific to CRC. RESULTS: Through
      constructing a transcription factor (TF)-module network, we found that aberrant
      DNA methylation of genes encoding TF considerably contributes to the activity
      change of some genes, which may function as causal genes of CRC, and that can
      also be exploited to develop efficient therapies or effective drugs. CONCLUSION:
      Our method can potentially be extended to the study of other complex diseases and
      the multiclassification problem.

PMID- 22967705
TI  - Identification of potential biomarkers to distinguish Mycobacterium colombiense
      from other mycobacterial species.
AB  - Mycobacterium avium complex (MAC) consists of 9 species of slow-growing
      mycobacteria with differing degrees of pathogenicity, host preference and
      environmental distribution. Mycobacterium colombiense is a novel member of MAC
      that is responsible for disseminated infections in HIV-infected patients in
      Colombia and lymphadenopathy cases in Europe. At present, methods to easily
      differentiate novel members of MAC are lacking. In this study, we identified
      possible biomarkers that are potentially useful for the detection of M.
      colombiense by PCR or chromatography. The Randomly Amplified Polymorphic DNA
      (RAPD) technique was used to amplify genomic fragments of M. colombiense CECT
      3035 that were subsequently used in the development of a direct colony-specific
      PCR assay using specific primers. The designed primers amplified a 634-bp
      fragment of DNA from M. colombiense, which included a 450-bp genomic region that
      encodes a hypothetical protein of 149 amino acids that is exclusive to M.
      colombiense. Bioinformatic analyses revealed that this hypothetical protein had
      no signal peptide, active sites or functional domains to aid its identification
      or classification. In addition, using thin-layer chromatography, we identified a
      different profile of mycolates for M. colombiense strains. The test developed in
      this study has potential applications in the routine identification of M.
      colombiense and in molecular assays designed for the surveillance of MAC strains.

PMID- 22967706
TI  - The lymph node ratio has limited prognostic significance in melanoma.
AB  - BACKGROUND: The importance of the lymph node ratio (LNR) after regional
      lymphadenectomy for cutaneous melanoma is unknown. MATERIALS AND METHODS: A post
      hoc analysis was performed for patients after the completion of lymphadenectomy
      for cutaneous melanoma. LNR was calculated as the number of tumor-positive nodes
      divided by the total number of lymph nodes. Comparison of disease-free survival
      (DFS) and overall survival (OS) and univariate and multivariate analyses with
      regard to LNR was performed. Comparison of the performance of LNR to other
      measurements of lymph node disease was performed. RESULTS: A LNR of 0.10 was a
      significant cutoff point for determining DFS and OS. On multivariate analysis,
      LNR >0.10 was an independent predictor of DFS and OS without other measures of
      lymph node disease burden. Patients with LNR >0.10 had worse DFS and OS. Absolute
      counts of tumor-positive lymph nodes differentiated survival differences better
      than LNR. LNR was not a significant predictor of survival in patients with neck
      or axillary dissections but was for inguinal dissections. In multivariate
      analysis of alternative nodal measures, LNR was an inferior prognostic factor.
      CONCLUSIONS: A LNR >0.10 has a negative prognostic significance when it is the
      only measurement of lymph node disease considered but is an inferior prognostic
      factor to alternative measures of lymph node disease.

PMID- 22967707
TI  - Effect of cyclin [corrected] D1 (CCND1) gene polymorphism on tumor formation and
      behavior in patients with prolactinoma.
AB  - The objective of this study was to investigate the effect of G870A gene
      polymorphism of CCND1 on the formation and behavioral features of prolactinomas.
      One hundred and thirteen patients with prolactinoma and 108 age and gender
      matched control were included in the study. The patients were divided into two
      groups as noninvasive and invasive tumors. CCND1 G870A gene polymorphism was
      compared in patients/control and invasive/noninvasive groups. A and G allele
      frequencies were found as 41.7% and 58.3% in the controls, and 61.1% and 38.9% in
      the patients (p<0.01). Rates of G/G, G/A and A/A genotypes were found as 11.8%,
      55.9% and 32.4% in the noninvasive group, and 15.6%, 44.4% and 40.0% in the
      invasive group, respectively. Differences between patient and control groups were
      significant but were not between invasive and noninvasive groups in terms of the
      allele frequencies and genotype distribution. Mean tumor size and serum levels of
      prolactin at the time of diagnosis and change in these values after the treatment
      were not found statistically significant in genotype subgroups. CCND1 G870A gene
      polymorphism may be an important factor in the early stages of the tumor
      formation. However, it did not affect the features of the tumor.

PMID- 22967708
TI  - Functional variants of 5S rRNA in the ribosomes of common sea urchin
      Paracentrotus lividus.
AB  - We have previously reported a molecular and cytogenetic characterization of three
      different 5S rDNA clusters in the sea urchin Paracentrotus lividus; this study,
      performed at DNA level only, lends itself as starting point to verify that these
      clusters could contain transcribed genes, then, to demonstrate the presence of
      heterogeneity at functional RNA level, also. In the present work we report in P.
      lividus ribosomes the existence of several transcribed variants of the 5S rRNA
      and we associate all transcribed variants to the cluster to which belong. Our
      finding is the first demonstration of the presence of high heterogeneity in
      functional 5S rRNA molecules in animal ribosomes, a feature that had been
      considered a peculiarity of some plants.

PMID- 22967709
TI  - 1alpha,25-dihydroxyvitamin D3 and rosiglitazone synergistically enhance
      osteoblast-mediated mineralization.
AB  - Both vitamin D receptor (VDR) and peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) are ligand-activated nuclear transcription factors that are
      instrumental for bone health. While 1alpha,25-dihydroxyvitamin D3 (1,25D3), the
      ligand for VDR, is essential for the development and maintenance of healthy bone,
      PPAR-gamma agonists cause detrimental skeletal effects. Recent studies have
      revealed evidence for a cross-talk between 1,25D3- and PPAR-alpha/-delta ligand
      mediated signaling but there is a current lack of knowledge regarding cross-talk
      between signaling of 1,25D3 and the PPAR-gamma ligand mediated signaling. In this
      study, we investigated the cross-talk between 1,25D3- and PPAR-gamma agonist
      rosiglitazone-mediated signaling in human osteoblasts. 1,25D3 slightly but
      significantly induced expression of the primary PPAR-gamma target gene ANGPTL4
      but did not influence FABP4. 1,25D3 did not change rosiglitazone regulation of
      ANGPTL4 and FABP4. The other way around, rosiglitazone reduced CYP24A1 gene
      expression but this did not change CYP24A1 induction by 1,25D3. The findings
      regarding CYP24A1 gene expression are in line with the observation that 1,25D3
      levels in medium were not affected by rosiglitazone. Furthermore, rosiglitazone
      significantly inhibited 1,25D3-induction of BGLAP while rosiglitazone alone did
      not change BGLAP. Additionally, 1,25D3 and rosiglitazone increase osteoblast
      alkaline phosphatase activity and synergistically stimulated extracellular matrix
      mineralization. In conclusion, these data provide evidence for a cross-talk
      between rosiglitazone- and 1,25D3-mediated signaling leading to an acceleration
      of extracellular matrix mineralization. The data suggest that the reduction of
      the mineralization inhibitor BGLAP and the increased differentiation status
      underlie the increased mineralization.

PMID- 22967711
TI  - Computational prediction of the polyQ and CAG repeat spinocerebellar ataxia
      network based on sequence identity to untranslated regions.
AB  - Computational prediction of biological networks would be a tremendous asset to
      systems biology and personalized medicine. In this paper, we use a moving window
      bioinformatic screen to identify transcripts with partial identity to the 5' and
      3'UTRs of the polyQ spinocerebellar ataxia (SCA) genes ATXN1, ATXN2, ATXN3,
      ATXN7, TBP and CACNA1A and the CAG repeat expansion gene PPP2R2B. We find that
      the bioinformatic screen enriches for transcripts that encode proteins that
      interact and that have functions relevant to polyQ SCA. Transcription control and
      RNA binding are the primary functional groups represented in the proteins from
      the combined screens. The insulin growth factor pathway, the WNT pathway, long
      term potentiation, melanogenesis and ATM mediated DNA repair pathways were
      identified as important pathways. UGUUU repeats were identified as an abundant
      motif in the SCA network and PAXIP1, CELF2, CREBBP, EBF1, PLEKHG4, SRSF4,
      C5orf42, NFIA, STK24, and YWHAG were identified as statistically significant
      proteins in the polyQ and PPP2R2B network.

PMID- 22967710
TI  - Comparison of genome diversity of Brucella spp. field isolates using Universal
      Bio-signature Detection Array and whole genome sequencing reveals limitations of
      current diagnostic methods.
AB  - The detection and identification of bio-threat agents and the study of host
      pathogen interactions require a high-resolution detection platform capable of
      discerning closely related species. Diverse analysis methods are used to identify
      pathogens, specifically Brucella species or biovars. In this study, we compared
      four diagnostic approaches including serology-based biochemical test, PCR assay,
      microarray analysis using a Universal Bio-signature Detection Array (UBDA) and
      whole genome "deep" sequencing for Brucella organisms including a number of field
      isolates. We found that although there was frequent agreement among the different
      tests, some tests gave compound/contradictory results that were a consequence of
      species diversity due to mixed infections or minor contaminants as measured by
      UBDA and validated from whole genome sequence. By comparing these analysis
      techniques, we demonstrate that standard diagnostics used in the field are
      limited in their ability to identify genomic DNA contaminants in field isolates
      while UBDA and sequencing analysis are highly sensitive in tracing genomic
      differences among the isolates.

PMID- 22967712
TI  - Association of three SNPs in interleukin-28B with graft hepatic  dysfunction
      after liver  transplantation in Chinese Han population.
AB  - BACKGROUND: Recurrent graft infection limited the effect of LT, early recognition
      and prophylaxis of HBV recurrence are very important, and interleukin 28B (IL
      28B) gene was reported to be associated with HBV infection. AIMS: To explore the
      association between IL-28B single-nucleotide polymorphisms (SNPs) and graft re
      infection after liver transplantation(LT). METHODS: 21 recipients with hepatitis
      B virus(HBV) recurrence and 157 recipients without HBV recurrence were included.
      We studied three SNPs in the promoter region of IL-28B gene at the positions
      rs12979860,rs12980275 and rs8099917 by HRM analysis (high-resolution melting
      curve analysis). RESULTS: Hepatic allograft dysfunction was more likely to be
      associated with IL-28B SNPs. However, there was no significant difference in the
      frequencies of IL-28B gene distribution in recipients with or without HBV
      recurrence. CONCLUSION: IL-28B gene polymorphism may be associated with the
      prognosis of LT recipients but it needs more experiments.

PMID- 22967713
TI  - Orbital myositis as manifestation of systemic lupus erythematosus--a case report.

PMID- 22967714
TI  - Enzyme-coupled assays for simultaneous detection of nanomolar ATP, ADP, AMP,
      adenosine, inosine and pyrophosphate concentrations in extracellular fluids.
AB  - Purinergic signaling cascade includes the release of endogenous ATP and other
      agonists by chemical and mechanical stimuli, modulation of diverse cellular
      functions and subsequent ectoenzymatic inactivation. Basal release of
      extracellular purines and its physiological relevance remain controversial. Here
      we employed a combination of enzyme-coupled approaches for simultaneous
      bioluminescent (ATP, ADP, PP(i)) and fluorometric (AMP), adenosine, inosine,
      hypoxanthine) measurements of ATP and its metabolites without additional
      manipulations or derivatization of sampled biological fluids. By using these
      sensing techniques, extracellular purines were determined in various cells and
      tissues both at resting and pro-inflammatory conditions. The results obtained
      revealed the ability of endothelial, lymphoid and tumor cells to maintain
      extracellular ATP, ADP and adenosine at certain characteristic nanomolar levels.
      By quantifying the amounts of endogenously released and/or exogenously applied
      purines and their metabolites, these sensing techniques may be applied for
      evaluating purine-converting pathways on the cell surfaces and also for ex vivo
      analysis of purine homeostasis in the intact tissues. Furthermore, we provide
      novel insight into the mechanisms underlying tumorigenic effects of ATP by
      demonstrating the ability of metastatic prostate carcinoma PC3 and breast cancer
      MDA-MB-231 cells to maintain PP(i), which derives from extracellular ATP in the
      course of nucleotide pyrophosphatase/phosphodiesterase reaction. Collectively,
      the results imply a complex pattern of nucleotide turnover where extracellular
      ATP, ADP and adenosine are maintained at steady-state levels via conunterbalanced
      release and inactivation of ATP and other purines, and further suggest the
      importance of basal agonist release for continuous activation and/or
      desensitization of purinergic receptors.

PMID- 22967715
TI  - Compression garments do not alter cerebrovascular responses to orthostatic stress
      after mild passive heating.
AB  - Whole-body heating increases the likelihood of syncope, whereas utilizing lower
      body compression garments may reduce syncope risk. We hypothesized that graded
      compression garments would reduce the typically observed large postural
      reductions in arterial blood pressure and middle cerebral artery velocity, in
      normothermia and especially once passively heat stressed. Fifteen men (age: 27 +/
      4 years, aerobic fitness range: 30-75 mL/kg(/) min) completed a supine-to-stand
      orthostatic challenge for 3 min at normothermia and after passive heating
      (esophageal temperature, +0.5  degrees C from baseline) on two occasions (> 7
      days): once wearing commercially available compression trousers and once wearing
      low-compression placebo trousers (randomized order). Blood flow velocity in the
      middle cerebral artery (transcranial Doppler), mean arterial blood pressure (mean
      BP: Finometer) and end-tidal carbon dioxide pressure were measured continuously.
      During normothermia, compression, garments did not alter the magnitude of the
      postural changes in mean BP or middle cerebral artery velocity. After passive
      heating, although the magnitudes of these changes were exaggerated, they were not
      significantly affected by compression garments. Compression garments did not
      attenuate the initial or sustained orthostatic hypotension associated with
      posture change, either during normothermia or following passive heat stress.

PMID- 22967716
TI  - Efficacy of brief alcohol screening intervention for college students (BASICS): a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Many studies reported that brief interventions are effective in
      reducing excessive drinking. This study aimed to assess the efficacy of a
      protocol of brief intervention for college students (BASICS), delivered face-to
      face, to reduce risky alcohol consumption and negative consequences. METHODS: A
      systematic review with meta-analysis was performed by searching for randomized
      controlled trials (RCTs) in Medline, PsycInfo, Web of Science and Cochrane
      Library databases. A quality assessment of RCTs was made by using a validated
      scale. Combined mean effect sizes, using meta-analysis random-effects models,
      were calculated. RESULTS: 18 studies were included in the review. The sample
      sizes ranged from 54 to 1275 (median=212). All studies presented a good
      evaluation of methodological quality and four were found to have excellent
      quality. After approximately 12 months of follow-up, students receiving BASICS
      showed a significant reduction in alcohol consumption (difference between means=
      1.50 drinks per week, 95% CI: -3.24 to -0.29) and alcohol-related problems
      (difference between means=-0.87, 95% CI: -1.58 to -0.20) compared to controls.
      CONCLUSIONS: Overall, BASICS lowered both alcohol consumption and negative
      consequences in college students. Gender and peer factors seem to play an
      important role as moderators of behavior change in college drinking.
      Characteristics of BASICS procedure have been evaluated as more favorable and
      acceptable by students in comparison with others interventions or control
      conditions. Considerations for future researches were discussed.

PMID- 22967717
TI  - Reconstruction for planned ventral hernia after surgery for generalised
      peritonitis: de-epithelialisation of split-thickness skin graft and
      transplantation of pedicled anterolateral thigh flap.

PMID- 22967718
TI  - A branching pattern of the facial nerve trunk with six initial branches: possible
      implications for parotid surgery?

PMID- 22967719
TI  - Early cosmetic outcomes with the use of skin adhesives: meta-analysis of
      randomized controlled trials.

PMID- 22967720
TI  - Return to work after stroke: the role of cognitive deficits.

PMID- 22967721
TI  - Logopenic progressive aphasia beyond Alzheimer's--an evolution towards dementia
      with Lewy bodies.

PMID- 22967722
TI  - Anti-obesity effects of glabridin-rich supercritical carbon dioxide extract of
      licorice in high-fat-fed obese mice.
AB  - Licorice (Glycyrrhiza glabra Linne) is a well-known medicinal plant and glabridin
      is an isoflavan isolated from licorice. In this study, we investigated the anti
      obesity effect of glabridin and glabridin-rich supercritical fluid extract of
      licorice (LSC). Glabridin effectively inhibited adipogenesis in 3T3-L1 cells.
      Moreover, LSC showed inhibitory effect on adipogenesis in a dose-dependent
      manner. The inhibitory effect of LSC resulted from inhibiting the induction of
      the transcriptional factors CCAAT enhancer binding protein alpha and peroxisome
      proliferator-activated receptor gamma. Then we fed mice with high-fat diet
      containing none, 0.1% and 0.25% LSC for 8weeks to explore the anti-obesity effect
      of LSC in vivo. LSC significantly reduced weight gain by high-fat diet in a dose
      dependent manner. The reductions of the hypertrophy of white adipose tissue and
      of fat cell size were also observed. In the liver, LSC supplementation
      effectively inhibited high-fat diet-induced hepatic steatosis through
      downregulation of gluconeogenesis related phosphoenolpyruvate carboxykinase and
      glucose 6-phosphatase and upregulation of the beta-oxidation related carnitine
      palmitoyltransferase 1. Taken together, our results suggest that glabridin and
      glabridin-rich licorice extract would be effective anti-obesity agents.

PMID- 22967723
TI  - 2,5-hexanedione altered the degradation of low-molecular-weight neurofilament in
      rat nerve tissues.
AB  - Occupational exposure to n-hexane produces a central-peripheral distal
      axonopathy, which is characterized by giant axonal swellings filled with
      neurofilaments (NFs). To investigate the change of NFs degradation and their
      possible role in n-hexane neuropathy, adult male Wistar rats were administered
      intraperitoneally at a dosage of 400 mg/kg/day 2,5-hexanedione (2,5-HD) for 4
      weeks. The time course of low-molecular-weight neurofilament (NF-L) degradation
      and autophagy-related protein in rat sciatic nerves and spinal cords was
      determined by Western blotting. The results demonstrated that the administration
      of 2,5-HD inhibited NF-L degradation to an undetectable level in sciatic nerves.
      Furthermore, a significant reduction of NF-L degradation in spinal cords was
      observed in the early stage of 2,5-HD exposure. In the meantime, 2,5-HD
      significantly decreased the level of Beclin-1, a key autophagy-regulated protein
      in sciatic nerves of rats while increased the level of P62, a selective substrate
      of autophagy degrading pathway, which indicated a dysfunctional autophagy in rat
      nerve tissues. Collectively, our findings suggested that the inhibition of
      autophagy by 2,5-HD might be responsible for the reduction of NF-L degradation in
      rat sciatic nerves, and involved in the pathogenesis of 2,5-HD-induced
      axonopathy.

PMID- 22967724
TI  - Cystic echinococcosis in slaughtered domestic ruminants from Tunisia.
AB  - A total of 10,818 domestic ruminants (3913 cattle, 2722 sheep, 3779 goats, 404
      dromedaries) slaughtered in various abattoirs in Tunisia between 2003 and 2010
      were examined for the presence of Echinococcus granulosus hydatid cysts. The
      prevalence of cystic echinococcosis (CE) was 16.42% in sheep, 8.56% in cattle,
      5.94% in dromedaries and 2.88% in goats. CE prevalence increased with age
      according to an asymptotic model and there was evidence of variation in infection
      pressure depending on the region of Tunisia where the animals were slaughtered.
      Cattle appeared to have the highest infection pressure of the species examined.
      The mean intensity of hepatic cysts was higher than that of pulmonary cysts in
      all species. The highest mean intensity of infection with E. granulosus larvae
      was observed in cattle (18.14) followed by sheep (9.58), goats (2.31) and
      dromedaries (2.12). The abundance of infection increased in a linear fashion with
      age in all animal species. Cyst abundance varied with species of animal and
      district of Tunisia. Cysts from dromedaries were more fertile (44.44%) than those
      from sheep (30.25%), goats (30.32%) and cattle (0.95%). The viability of the
      protoscoleces from fertile cysts from cattle (78.45%) was higher than those from
      sheep (70.71%) and camels (69.57%). The lowest protoscolex viability was recorded
      for hydatid cysts from goats (20.21%). This epidemiological study confirms the
      importance of CE in all domestic ruminant species, particularly in sheep,
      throughout Tunisia and emphasizes the need to interrupt parasite transmission by
      preventive integrated approaches in a CE control programme. 

PMID- 22967727
TI  - Minimal excess mortality for long-term colon cancer survivors in the Netherlands
      1989-2008.
AB  - We determined conditional 5-year relative survival rates for colon cancer
      patients, according to age, gender and tumour stage for each additional year of
      survival up to 15 years after diagnosis. All 89,451 patients diagnosed in the
      Netherlands with colon cancer stage I-III in 1989-2008 aged 15-89 years were
      selected from the Netherlands Cancer Registry. Conditional 5-year relative
      survival was computed for every additional year of survival up to 15 years. There
      was minimal excess mortality (conditional 5-year relative survival >95%) 1-4
      years after diagnosis of stage I patients and 4-7 years after diagnosis of stage
      II patients, with patients aged 45-74 years reaching this point later compared to
      both younger and elderly patients. For stage III patients, minimal excess
      mortality was observed 5 years after diagnosis for those aged 75-89 years, but it
      remained elevated up to 13 years after diagnosis for those aged 15-44 years.
      Initial differences in relative survival at diagnosis between age and stage
      groups largely disappeared with increasing number of years survived. The
      prognosis for colon cancer survivors improved with each additional year survived.
      In the first years after diagnosis conditional survival improved largely for all
      colon cancer patients, especially for stage III patients. There was minimal
      excess mortality for colon cancer patients stage I-III at some point within 15
      years of diagnosis, being later for more advanced stages. Quantitative insight
      into conditional survival for cancer patients is useful for caregivers to help
      plan optimal cancer surveillance and inform patients about their prognosis.

PMID- 22967726
TI  - Localised angiosarcomas: the identification of prognostic factors and analysis of
      treatment impact. A retrospective analysis from the French Sarcoma Group
      (GSF/GETO).
AB  - BACKGROUND: Angiosarcomas represent less than 2% of all adult soft tissue
      sarcomas. Prognostic factors and the role of (neo-) adjuvant treatments in the
      management of localised angiosarcomas require further investigation. METHODS: We
      have conducted a retrospective multicenter study (June 1980 to October 2009) of
      107 patients with localised angiosarcomas. All of the cases were centrally
      reviewed by a certified pathologist. Univariate and multivariate analyses were
      conducted to identify independent poor prognostic factors (PF). Overall survival
      (OS) and Local Recurrence-Free Survival (LRFS) were estimated using the Kaplan
      Meier method. The effect of treatments was explored using the Cox model after
      adjusting for the PF. RESULTS: The median age was 71 years. 22.4% and 62.6%
      developed an angiosarcoma in pre-existing lymphoedema and within irradiated
      tissue respectively. The median OS, LRFS and Disease Recurrence-Free Survival
      (DRFS) were 38.8, 27 and 36.1 months, respectively. In multivariate analysis, the
      following parameters influenced the OS: lymphoedema (Hazard ratio (HR)=2.0) and
      size >5cm (HR=1.5). After adjustment to these PF, R0 margins was the only
      treatment parameter that improving the OS (HR=0.2). In the multivariate analysis,
      the LRFS was influenced by an age >70 (HR=1.8) and pre-existing lymphoedema
      (HR=2.0). After adjustment for these PF, R0 margins (HR=0.5) and adjuvant
      radiotherapy (HR=0.3) improved the LRFS. CONCLUSIONS: Our results suggest the
      following points: (i) pre-existing lymphoedema, tumour size and age >70 are
      probably the major prognostic factors in patients with localised angiosarcomas;
      (ii) the achievement of R0 margins is probably of major importance for improving
      the patient outcome and (iii) adjuvant radiotherapy probably decreased the risk
      of local recurrence.

PMID- 22967725
TI  - Nod2-induced autocrine interleukin-1 alters signaling by ERK and p38 to
      differentially regulate secretion of inflammatory cytokines.
AB  - BACKGROUND & AIMS: Stimulation of nucleotide-binding oligomerization domain
      containing (Nod)2 and other pattern recognition receptors (PRR) in human monocyte
      derived macrophages induces interleukin (IL)-1, which increases mitogen-activated
      protein kinase (MAPK) activation and cytokine secretion. Activation of MAPK by
      PRR has varied effects on inflammatory cytokine secretion. We investigated
      whether different levels of autocrine IL-1 mediate these varied effects. METHODS:
      Macrophage responses to PRR ligands were analyzed by enzyme-linked immunosorbent
      assay and flow cytometry. We overexpressed or reduced MAPK levels (using small
      inhibitory RNA). RESULTS: Nod2 and other PRR activated signaling via
      extracellular signal-related kinase (ERK) and p38 that inhibited inflammatory
      cytokine production by human monocyte-derived macrophages; autocrine IL-1
      production prevented this inhibition. ERK and p38 inhibited inflammatory cytokine
      production by human macrophages that produce low levels of IL-1 (such as M2,
      endotoxin-tolerant, and intestinal macrophages); adding exogenous IL-1 caused ERK
      and p38 to stimulate production of inflammatory cytokines in these cells. In
      mouse macrophages, which do not produce IL-1 in response to PRR stimulation
      alone, addition of exogenous IL-1 reversed the ERK-mediated inhibition of IL
      12p40. Increasing activation of c-Jun N-terminal kinase in Nod2-stimulated human
      monocyte-derived macrophages, in the absence of autocrine IL-1 signaling, caused
      ERK and p38 to stimulate inflammatory cytokines secretion. Importantly, infection
      of human intestinal macrophages with pathogens that induce IL-1 production
      reversed the inhibition of inflammatory cytokine production by ERK and p38.
      CONCLUSIONS: In response to PRR stimulation of macrophages, the level of MAPK
      signaling is regulated by autocrine IL-1 and determines whether production of
      inflammatory cytokines is inhibited or stimulated. This mechanism could account
      for reported differences in MAPK regulation of inflammatory cytokines and
      propagate the inflammatory response to pathogens.

PMID- 22967728
TI  - The explanatory models of depression and anxiety in primary care: a qualitative
      study from India.
AB  - BACKGROUND: The biggest barrier to treatment of common mental disorders in
      primary care settings is low recognition among health care providers. This study
      attempts to explore the explanatory models of common mental disorders (CMD) with
      the goal of identifying how they could help in improving the recognition, leading
      to effective treatment in primary care. RESULTS: The paper describes findings of
      a cross sectional qualitative study nested within a large randomized controlled
      trial (the Manas trial). Semi structured interviews were conducted with 117
      primary health care attendees (30 males and 87 females) suffering from CMD. Main
      findings of the study are that somatic phenomena were by far the most frequent
      presenting problems; however, psychological phenomena were relatively easily
      elicited on probing. Somatic phenomena were located within a biopsychosocial
      framework, and a substantial proportion of informants used the psychological
      construct of 'tension' or 'worry' to label their illness, but did not consider
      themselves as suffering from a 'mental disorder'. Very few gender differences
      were observed in the descriptions of symptoms but at the same time the pattern of
      adverse life events and social difficulties varied across gender. CONCLUSION: Our
      study demonstrates how people present their illness through somatic complaints
      but clearly link their illness to their psychosocial world. However they do not
      associate their illness to a 'mental disorder' and this is an important
      phenomenon that needs to be recognized in management of CMD in primary settings.
      Our study also elicits important gender differences in the experience of CMD.

PMID- 22967729
TI  - Illicit drug use in cluster headache patients and in the general population: a
      comparative cross-sectional survey.
AB  - BACKGROUND: The rate of illicit drug use in cluster headache (CH) patients is
      unknown. METHODS: Two hundred and ten CH patients (162 males and 48 females)
      attending two headache clinics provided information about their lifetime use
      (once or more in their lifetime, LTU), recent use (once or more in the past year,
      RU), and current use (once or more in the past 30 days, CU) of illicit drugs.
      General population data (IPSAD(r)Italia2007-2008) served as the control group.
      RESULTS: LTU of each illicit drug but hallucinogens, RU of cannabis, cocaine,
      amphetamines and ecstasy, and CU of cannabis and cocaine were significantly
      higher in the male CH patients than in the general population, whereas no
      difference was found between the CH women and the controls. In the CH group,
      28.5% of patients reported having used illicit drugs for the first time after CH
      onset and 71.5% before CH onset. Compared with the controls, the male CH group
      showed a greater prevalence both of lifetime sustained intensive use of any
      illicit drug and of current intensive use of cannabis. CONCLUSION: The results of
      this study indicate that male CH patients are prone to overindulge in illicit
      drug use. This finding possibly reflects a common biological susceptibility that
      predisposes these subjects to CH and to addictive behaviour.

PMID- 22967730
TI  - Acute effects of deltamethrin on swimming velocity and biomarkers of the common
      prawn Palaemon serratus.
AB  - The main purpose of the present study was to investigate the effects of
      deltamethrin on biomarkers and behavior of Palaemon serratus (common prawn),
      since this attempt to link different levels of biological organization will allow
      determining which biomarkers might be ecologically relevant and will be useful to
      complement the information about the effects of pesticides by using behavioral
      parameters. Therefore, parameters of liver antioxidant status, energy metabolism
      and neurotransmission were determined in different tissues of the common prawn
      and used to assess the effects at sub-individual level, whereas swimming velocity
      was used to assess the effects at the individual level. It was also investigated
      if the swimming velocity can be used as an endpoint in ecotoxicology bioassays
      and if it can be as sensitive as biomarker endpoints. Swimming velocity was
      significantly reduced in prawns exposed to deltamethrin, showing a lowest
      observed effect (LOEC) of 0.6 ng L(-1). Eye acetylcholinesterase (AChE) activity
      was significantly increased in prawns exposed to 0.6, 1.2 and 2.4 ng L(-1)
      deltamethrin, whereas muscle cholinesterase (ChE) activity was significantly
      increased in prawns exposed to 19 and 39 ng L(-1). On the other hand, lactate
      dehydrogenase (LDH) activity was significantly increased in muscle of prawns
      exposed to 0.6, 1.2, 2.4, 4.9 ng L(-1) deltamethrin, showing that organisms were
      requiring additional energy, but probably using it for detoxification processes
      rather than locomotion, since swimming velocity was inhibited. Glutathione S
      transferase (GST) activity was significantly increased in the digestive gland of
      common prawn exposed to 19 and 39 ng L(-1) deltamethrin. Catalase (CAT) activity
      was significantly increased in digestive gland of prawn exposed to 19 ng L(-1)
      deltamethrin. However, CAT activity decreased in digestive gland of prawn exposed
      to 39 ng L(-1), suggesting an antioxidant defense system failure concomitant with
      high levels of lipid peroxidation. Thus, global results showed that decreased
      swimming velocity was not associated with cholinesterase inhibition. In fact, the
      impairment of swimming velocity may be due to allocation of energy for
      detoxification and antioxidant protection instead of swimming activity. The
      present study showed that swimming velocity could be used as an ecologically
      relevant tool and a sensitive endpoint to assess and complement the study of
      pesticide effects on marine organisms.

PMID- 22967732
TI  - The usefulness of bedside testing in assessments of peripheral vestibular system
      function.

PMID- 22967733
TI  - Working memory capacity may influence perceived effort during aided speech
      recognition in noise.
AB  - BACKGROUND: Recently there has been interest in using subjective ratings as a
      measure of perceived effort during speech recognition in noise. Perceived effort
      may be an indicator of cognitive load. Thus, subjective effort ratings during
      speech recognition in noise may covary both with signal-to-noise ratio (SNR) and
      individual cognitive capacity. PURPOSE: The present study investigated the
      relation between subjective ratings of the effort involved in listening to speech
      in noise, speech recognition performance, and individual working memory (WM)
      capacity in hearing impaired hearing aid users. RESEARCH DESIGN: In two
      experiments, participants with hearing loss rated perceived effort during aided
      speech perception in noise. Noise type and SNR were manipulated in both
      experiments, and in the second experiment hearing aid compression release
      settings were also manipulated. Speech recognition performance was measured along
      with WM capacity. STUDY SAMPLE: There were 46 participants in all with bilateral
      mild to moderate sloping hearing loss. In Experiment 1 there were 16 native
      Danish speakers (eight women and eight men) with a mean age of 63.5 yr (SD =
      12.1) and average pure tone (PT) threshold of 47. 6 dB (SD = 9.8). In Experiment
      2 there were 30 native Swedish speakers (19 women and 11 men) with a mean age of
      70 yr (SD = 7.8) and average PT threshold of 45.8 dB (SD = 6.6). DATA COLLECTION
      AND ANALYSIS: A visual analog scale (VAS) was used for effort rating in both
      experiments. In Experiment 1, effort was rated at individually adapted SNRs while
      in Experiment 2 it was rated at fixed SNRs. Speech recognition in noise
      performance was measured using adaptive procedures in both experiments with
      Dantale II sentences in Experiment 1 and Hagerman sentences in Experiment 2. WM
      capacity was measured using a letter-monitoring task in Experiment 1 and the
      reading span task in Experiment 2. RESULTS: In both experiments, there was a
      strong and significant relation between rated effort and SNR that was independent
      of individual WM capacity, whereas the relation between rated effort and noise
      type seemed to be influenced by individual WM capacity. Experiment 2 showed that
      hearing aid compression setting influenced rated effort. CONCLUSIONS: Subjective
      ratings of the effort involved in speech recognition in noise reflect SNRs, and
      individual cognitive capacity seems to influence relative rating of noise type.

PMID- 22967731
TI  - Neural similarity between encoding and retrieval is related to memory via
      hippocampal interactions.
AB  - A fundamental principle in memory research is that memory is a function of the
      similarity between encoding and retrieval operations. Consistent with this
      principle, many neurobiological models of declarative memory assume that memory
      traces are stored in cortical regions, and the hippocampus facilitates the
      reactivation of these traces during retrieval. The present investigation tested
      the novel prediction that encoding-retrieval similarity can be observed and
      related to memory at the level of individual items. Multivariate representational
      similarity analysis was applied to functional magnetic resonance imaging data
      collected during encoding and retrieval of emotional and neutral scenes. Memory
      success tracked fluctuations in encoding-retrieval similarity across frontal and
      posterior cortices. Importantly, memory effects in posterior regions reflected
      increased similarity between item-specific representations during successful
      recognition. Mediation analyses revealed that the hippocampus mediated the link
      between cortical similarity and memory success, providing crucial evidence for
      hippocampal-cortical interactions during retrieval. Finally, because emotional
      arousal is known to modulate both perceptual and memory processes, similarity
      effects were compared for emotional and neutral scenes. Emotional arousal was
      associated with enhanced similarity between encoding and retrieval patterns.
      These findings speak to the promise of pattern similarity measures for evaluating
      memory representations and hippocampal-cortical interactions. 

PMID- 22967734
TI  - The Revised Speech Perception in Noise Test (R-SPIN) in a multiple signal-to
      noise ratio paradigm.
AB  - BACKGROUND: The Revised Speech Perception in Noise Test (R-SPIN; Bilger, 1984b)
      is composed of 200 target words distributed as the last words in 200 low
      predictability (LP) and 200 high-predictability (HP) sentences. Four list pairs,
      each consisting of two 50-sentence lists, were constructed with the target word
      in a LP and HP sentence. Traditionally the R-SPIN is presented at a signal-to
      noise ratio (SNR, S/N) of 8 dB with the listener task to repeat the last word in
      the sentence. PURPOSE: The purpose was to determine the practicality of altering
      the R-SPIN format from a single SNR paradigm into a multiple SNR paradigm from
      which the 50% points for the HP and LP sentences can be calculated. RESEARCH
      DESIGN: Three repeated measures experiments were conducted. STUDY SAMPLE: Forty
      listeners with normal hearing and 184 older listeners with pure-tone hearing loss
      participated in the sequence of experiments. DATA COLLECTION AND ANALYSIS: The R
      SPIN sentences were edited digitally (1) to maintain the temporal relation
      between the sentences and babble, (2) to establish the SNRs, and (3) to mix the
      speech and noise signals to obtain SNRs between -1 and 23 dB. All materials were
      recorded on CD and were presented through an earphone with the responses recorded
      and analyzed at the token level. For reference purposes the Words-in-Noise Test
      (WIN) was included in the first experiment. RESULTS: In Experiment 1, recognition
      performances by listeners with normal hearing were better than performances by
      listeners with hearing loss. For both groups, performances on the HP materials
      were better than performances on the LP materials. Performances on the LP
      materials and on the WIN were similar. Performances at 8 dB S/N were the same
      with the traditional fixed level presentation and the descending presentation
      level paradigms. The results from Experiment 2 demonstrated that the four list
      pairs of R-SPIN materials produced good first approximation psychometric
      functions over the -4 to 23 dB S/N range, but there were irregularities. The data
      from Experiment 2 were used in Experiment 3 to guide the selection of the words
      to be used at the various SNRs that would provide homogeneous performances at
      each SNR and would produce systematic psychometric functions. In Experiment 3,
      the 50% points were in good agreement for the LP and HP conditions within both
      groups of listeners. The psychometric functions for List Pairs 1 and 2, 3 and 4,
      and 5 and 6 had similar characteristics and maintained reasonable separations
      between the HP and LP functions, whereas the HP and LP functions for List Pair 7
      and 8 bisected one another at the lower SNRs. CONCLUSIONS: This study indicates
      that the R-SPIN can be configured into a multiple SNR paradigm. A more in-depth
      study with the R-SPIN materials is needed to develop lists that are systematic
      and reasonably equivalent for use on listeners with hearing loss. The approach
      should be based on the psychometric characteristics of the 200 HP and 200 LP
      sentences with the current R-SPIN lists discarded. Of importance is maintaining
      the synchrony between the sentences and their accompanying babble.

PMID- 22967735
TI  - Evaluation of a transient noise reduction strategy for hearing AIDS.
AB  - BACKGROUND: Transient noise can be disruptive for people wearing hearing aids.
      Ideally, the transient noise should be detected and controlled by the signal
      processor without disrupting speech and other intended input signals. A
      technology for detecting and controlling transient noises in hearing aids was
      evaluated in this study. PURPOSE: The purpose of this study was to evaluate the
      effectiveness of a transient noise reduction strategy on various transient noises
      and to determine whether the strategy has a negative impact on sound quality of
      intended speech inputs. RESEARCH DESIGN: This was a quasi-experimental study. The
      study involved 24 hearing aid users. Each participant was asked to rate the
      parameters of speech clarity, transient noise loudness, and overall impression
      for speech stimuli under the algorithm-on and algorithm-off conditions. During
      the evaluation, three types of stimuli were used: transient noises, speech, and
      background noises. The transient noises included "knife on a ceramic board," "mug
      on a tabletop," "office door slamming," "car door slamming," and "pen tapping on
      countertop." The speech sentences used for the test were presented by a male
      speaker in Mandarin. The background noises included "party noise" and "traffic
      noise." All of these sounds were combined into five listening situations: (1)
      speech only, (2) transient noise only, (3) speech and transient noise, (4)
      background noise and transient noise, and (5) speech and background noise and
      transient noise. RESULTS: There was no significant difference on the ratings of
      speech clarity between the algorithm-on and algorithm-off (t-test, p = 0.103).
      Further analysis revealed that speech clarity was significant better at 70 dB SLP
      than 55 dB SPL (p < 0.001). For transient noise loudness: under the algorithm-off
      condition, the percentages of subjects rating the transient noise to be somewhat
      soft, appropriate, somewhat loud, and too loud were 0.2, 47.1, 29.6, and 23.1%,
      respectively. The corresponding percentages under the algorithm-on were 3.0,
      72.6, 22.9, and 1.4%, respectively. A significant difference on the ratings of
      the transient noise loudness was found between the algorithm-on and algorithm-off
      (t-test, p < 0.001). For overall impression for speech stimuli: under the
      algorithm-off condition, the percentage of subjects rating the algorithm to be
      not helpful at all, somewhat helpful, helpful, and very helpful for speech
      stimuli were 36.5, 20.8, 33.9, and 8.9%, respectively. Under the algorithm-on
      condition, the corresponding percentages were 35.0, 19.3, 30.7, and 15.0%,
      respectively. Statistical analysis revealed there was a significant difference on
      the ratings of overall impression on speech stimuli. The ratings under the
      algorithm-on condition were significantly more helpful for speech understanding
      than the ratings under algorithm-off (t-test, p < 0.001). CONCLUSIONS: The
      transient noise reduction strategy appropriately controlled the loudness for most
      of the transient noises and did not affect the sound quality, which could be
      beneficial to hearing aid wearers.

PMID- 22967736
TI  - Performance of Fukuda Stepping Test as a function of the severity of caloric
      weakness in chronic dizzy patients.
AB  - BACKGROUND: The purpose of the Fukuda Stepping Test (FST) is to measure
      asymmetrical vestibulospinal reflex tone resulting from labyrinthine dysfunction.
      The FST is a low cost evaluation for dizzy patients; however, when compared with
      gold standard caloric irrigation unilateral weakness (UW) value >=25%, the FST
      has not been shown to be a sensitive tool for identifying unilateral vestibular
      hypofunction. PURPOSE: The purpose of this technical report is to further
      evaluate the clinical utility of FST with and without headshake as a function of
      increased caloric asymmetry for individuals with unilateral peripheral vestibular
      pathology. RESEARCH DESIGN: Retrospective review of FST results with and without
      head shaking component as compared to gold standard, caloric irrigation UW
      outcome values at four severity levels: 0-24% UW (normal caloric value); 25-50%
      UW (mild caloric UW); 51-75% UW (moderate caloric UW); 76-100% UW (severe caloric
      UW). STUDY SAMPLE: 736 chronic (>=8 wk symptom complaints) dizzy patients.
      RESULTS: Standard FST and FST following a head shake task are insensitive to
      detecting mild to moderate peripheral vestibular paresis. Increased test
      performance was observed for patients with severe canal paresis (>76% UW);
      however, continued inconsistencies were found in turn direction toward the severe
      unilateral vestibular dysfunction. CONCLUSIONS: Overall, the FST provides little
      benefit to clinicians when used in the vestibular bedside examination.

PMID- 22967737
TI  - Using patient perceptions of relative benefit and enjoyment to assess auditory
      training.
AB  - BACKGROUND: Patients seeking treatment for hearing-related communication
      difficulties are often disappointed with the eventual outcomes, even after they
      receive a hearing aid or a cochlear implant. One approach that audiologists have
      used to improve communication outcomes is to provide auditory training (AT), but
      compliance rates for completing AT programs are notoriously low. PURPOSE: The
      primary purpose of the investigation was to conduct a patient-based evaluation of
      the benefits of an AT program, I Hear What You Mean, in order to determine how
      the AT experience might be improved. A secondary purpose was to examine whether
      patient perceptions of the AT experience varied depending on whether they were
      trained with a single talker's voice or heard training materials from multiple
      talkers. RESEARCH DESIGN: Participants completed a 6 wk auditory training program
      and were asked to respond to a posttraining questionnaire. Half of the
      participants heard the training materials spoken by six different talkers, and
      half heard the materials produced by only one of the six talkers. STUDY SAMPLE:
      Participants included 78 adult hearing-aid users and 15 cochlear-implant users
      for a total of 93 participants who completed the study, ages 18 to 89 yr (M = 66
      yr, SD = 16.67 yr). Forty-three females and 50 males participated. The mean
      better ear pure-tone average for the participants was 56 dB HL (SD = 25 dB).
      INTERVENTION: Participants completed the single- or multiple-talker version of
      the 6 wk computerized AT program, I Hear What You Mean, followed by completion of
      a posttraining questionnaire in order to rate the benefits of overall training
      and the training activities and to describe what they liked best and what they
      liked least. DATA COLLECTION AND ANALYSIS: After completing a 6 wk computerized
      AT program, participants completed a posttraining questionnaire. Seven-point
      Likert scaled responses to whether understanding spoken language had improved
      were converted to individualized z scores and analyzed for changes due to AT.
      Written responses were coded and categorized to consider both positive and
      negative subjective opinions of the AT program. Regression analyses were
      conducted to examine the relationship between perceived effort and perceived
      benefit and to identify factors that predict overall program enjoyment. RESULTS:
      Participants reported improvements in their abilities to recognize spoken
      language and in their self-confidence as a result of participating in AT. Few
      differences were observed between reports from those trained with one versus six
      different talkers. Correlations between perceived benefit and enjoyment were not
      significant, and only participant age added unique variance to predicting program
      enjoyment. CONCLUSIONS: Participants perceived AT to be beneficial. Perceived
      benefit did not correlate with perceived enjoyment. Compliance with computerized
      AT programs might be enhanced if patients have regular contact with a hearing
      professional and train with meaning-based materials. An unheralded benefit of AT
      may be an increased sense of control over the hearing loss. In future efforts, we
      might aim to make training more engaging and entertaining, and less tedious.

PMID- 22967739
TI  - Peripheral arterial disease affects the frequency response of ground reaction
      forces during walking.
AB  - BACKGROUND: Walking is problematic for patients with peripheral arterial disease.
      The purpose of this study was to investigate the frequency domain of the ground
      reaction forces during walking to further elucidate the ambulatory impairment of
      these patients. METHODS: Nineteen bilateral peripheral arterial disease patients
      and nineteen controls were included in this study. Subjects were matched for age
      and gait speed. Participants walked over a force plate sampling at 600 Hz. PAD
      patients were tested before (pain-free condition) after the onset of claudication
      symptoms (pain). We calculated median frequency, frequency bandwidth, and
      frequency containing 99.5% of the signal for the vertical and anterior-posterior
      ground reaction forces. FINDINGS: Our results showed reduced median frequency in
      the vertical and anterior-posterior components of the ground reaction forces
      between the control group and both peripheral arterial disease conditions. We
      found reduced frequency bandwidth in the anterior-posterior direction between
      controls and the peripheral arterial disease pain-free condition. There were no
      differences in median frequency or bandwidth between peripheral arterial disease
      pain-free and pain conditions, but an increase in the frequency content for 99.5%
      of the signal was observed in the pain condition. INTERPRETATION: Reduced
      frequency phenomena during gait in peripheral arterial disease patients compared
      to velocity-matched controls suggests more sluggish activity within the
      neuromotor system. Increased frequency phenomena due to pain in these patients
      suggest a more erratic application of propulsive forces when walking. Frequency
      domain analysis thus offers new insights into the gait impairments associated
      with this patient population.

PMID- 22967738
TI  - Central presbycusis: a review and evaluation of the evidence.
AB  - BACKGROUND: The authors reviewed the evidence regarding the existence of age
      related declines in central auditory processes and the consequences of any such
      declines for everyday communication. PURPOSE: This report summarizes the review
      process and presents its findings. DATA COLLECTION AND ANALYSIS: The authors
      reviewed 165 articles germane to central presbycusis. Of the 165 articles, 132
      articles with a focus on human behavioral measures for either speech or nonspeech
      stimuli were selected for further analysis. RESULTS: For 76 smaller-scale studies
      of speech understanding in older adults reviewed, the following findings emerged:
      (1) the three most commonly studied behavioral measures were speech in
      competition, temporally distorted speech, and binaural speech perception
      (especially dichotic listening); (2) for speech in competition and temporally
      degraded speech, hearing loss proved to have a significant negative effect on
      performance in most of the laboratory studies; (3) significant negative effects
      of age, unconfounded by hearing loss, were observed in most of the studies of
      speech in competing speech, time-compressed speech, and binaural speech
      perception; and (4) the influence of cognitive processing on speech understanding
      has been examined much less frequently, but when included, significant positive
      associations with speech understanding were observed. For 36 smaller-scale
      studies of the perception of nonspeech stimuli by older adults reviewed, the
      following findings emerged: (1) the three most frequently studied behavioral
      measures were gap detection, temporal discrimination, and temporal-order
      discrimination or identification; (2) hearing loss was seldom a significant
      factor; and (3) negative effects of age were almost always observed. For 18
      studies reviewed that made use of test batteries and medium-to-large sample
      sizes, the following findings emerged: (1) all studies included speech-based
      measures of auditory processing; (2) 4 of the 18 studies included nonspeech
      stimuli; (3) for the speech-based measures, monaural speech in a competing-speech
      background, dichotic speech, and monaural time-compressed speech were
      investigated most frequently; (4) the most frequently used tests were the
      Synthetic Sentence Identification (SSI) test with Ipsilateral Competing Message
      (ICM), the Dichotic Sentence Identification (DSI) test, and time-compressed
      speech; (5) many of these studies using speech-based measures reported
      significant effects of age, but most of these studies were confounded by declines
      in hearing, cognition, or both; (6) for nonspeech auditory-processing measures,
      the focus was on measures of temporal processing in all four studies; (7) effects
      of cognition on nonspeech measures of auditory processing have been studied less
      frequently, with mixed results, whereas the effects of hearing loss on
      performance were minimal due to judicious selection of stimuli; and (8) there is
      a paucity of observational studies using test batteries and longitudinal designs.
      CONCLUSIONS: Based on this review of the scientific literature, there is
      insufficient evidence to confirm the existence of central presbycusis as an
      isolated entity. On the other hand, recent evidence has been accumulating in
      support of the existence of central presbycusis as a multifactorial condition
      that involves age- and/or disease-related changes in the auditory system and in
      the brain. Moreover, there is a clear need for additional research in this area.

PMID- 22967740
TI  - Tolerance of the lumbar spine to shear: a review and recommended exposure limits.
AB  - BACKGROUND: The lumbar spine may experience significant shear forces during
      occupational tasks due to the force of gravity acting on the upper body when
      bending the trunk forward, or when performing tasks involving pushing or pulling.
      Shear force limits of 1000 N and 500 N have been recommended by previous authors
      for maximum permissible limit and action limit, respectively. METHODS: The
      present paper reviews literature in terms of shear tolerance (ultimate shear
      stress and fatigue life in shear stress) of the lumbar spine and develops
      recommended limits based on results of studies examining shear loading of human
      motion segments. Weibull analysis was used to assess fatigue failure data to
      estimate distributions of failure at different percentages of ultimate shear
      stress. FINDINGS: Based on Weibull analysis of fatigue failure data from the best
      available data, a 1000 N shear limit would appear acceptable for occasional
      exposure to shear loading (<= 100 loadings/day); however, a 700 N limit would
      appear appropriate for repetitive shear loading (100-1000 loadings/day) for most
      workers. INTERPRETATION: Results of the current analysis support the 1000 N limit
      for shear stress, but for a rather limited number of cycles (<100 per day). Due
      to the logarithmic nature of the fatigue failure curve, a 700 N shear limit would
      appear to be acceptable for frequent shear loadings (100-1000 per day). This
      value is slightly higher than the action limit of 500 N previously recommended.

PMID- 22967741
TI  - Spatial and temporal expressions of prune reveal a role in Muller gliogenesis
      during Xenopus retinal development.
AB  - The development of stratified retinal cell architecture is highly conserved in
      all vertebrates, implying that a common fundamental molecular mechanism is
      involved in the generation of the organized retina. However, the detailed
      molecular mechanisms of retinal development are not fully understood. Here we
      have identified the Xenopus ortholog of prune and show that it is expressed in
      both differentiating and differentiated retinal domains during development.
      Interestingly, these spatial and temporal expression patterns coincide with the
      expression of prune binding partners, the NM23 family members. Overexpression of
      prune in retinal precursor cells significantly increases the ratio of Muller
      glial cells as observed by modulation of NM23 activity (Mochizuki et al., 2009).
      However, a mutated form of prune that has replacement of four aspartate (D)
      residues (D'Angelo et al., 2004), essential for phosphodiesterase activity, does
      not exhibit gliogenic activity. Our observations suggest that Xenopus prune may
      regulate Muller gliogenesis through phosphodiesterase-mediated regulation of NM23
      family members.

PMID- 22967743
TI  - Alterations of neocortical development and maturation in autism: insight from
      valproic acid exposure and animal models of autism.
AB  - Autism spectrum disorder (ASD) is a behaviourally defined brain disorder
      affecting approximately 1 in 88 children. Many pathological studies have shown
      that ASD is frequently associated with grey and white matter changes that can be
      described by their deviations from the normal trajectory of cortical maturation.
      For example, during the early (i.e. <2 years) postnatal period there is marked
      and selective tissue overgrowth in the higher-order temporal and frontal networks
      involved in emotional, social, and communication functions. In this focused
      review we first summarize some basic principles of neocortical neural
      organization and how they are disrupted in ASD. We will then highlight some of
      the potential mechanisms by which the normal developmental trajectory and
      organization of neocortical networks can be altered based on animal studies of
      valproic acid, a teratogen widely used in animal models of ASD. We argue that the
      trajectory of postnatal cerebral neocortex development may be influenced by
      several cellular and molecular mechanisms that may all converge to produce a
      neuropathology characterized by premature or accelerated neuronal growth.

PMID- 22967742
TI  - Reproductive and hormonal factors in relation to incidence of sarcoidosis in US
      Black women: The Black Women's Health Study.
AB  - The authors assessed the relation of hormonal and pregnancy-related factors to
      the incidence of sarcoidosis in the Black Women's Health Study. On biennial
      questionnaires, participants (US black women aged 21-69 years at baseline)
      reported data on diagnoses of sarcoidosis, reproductive history, and medication
      use. Cox regression models, adjusted for age, education, geographic region,
      smoking, and body mass index, were used to estimate incidence rate ratios and 95%
      confidence intervals. During 694,818 person-years of follow-up from 1995 through
      2009, 452 incident cases of sarcoidosis were identified. The incidence of
      sarcoidosis decreased as age at menopause increased (P-trend = 0.03). Both later
      age at first full-term birth and having a more recent birth were associated with
      a reduced incidence of sarcoidosis. In models that included both factors, the
      incidence rate ratios were 0.60 (95% confidence interval: 0.37, 0.97) for age at
      first birth >=30 years versus <20 years (P-trend = 0.05) and 0.73 (95% confidence
      interval: 0.43, 1.24) for <5 years since last birth versus >=15 years (P-trend =
      0.15). No significant associations were observed with age at menarche, parity,
      lactation, oral contraceptive use, or female hormone use. These results suggest
      that later full-term pregnancy and longer exposure to endogenous female hormones
      may be related to a reduced risk of sarcoidosis.

PMID- 22967744
TI  - Transcriptional responses in rat brain associated with sub-chronic toluene
      inhalation are not predicted by effects of acute toluene inhalation.
AB  - A primary public health concern regarding environmental chemicals is the
      potential for persistent effects from long-term exposure, and approaches to
      estimate these effects from short-term exposures are needed. Toluene, a
      ubiquitous air pollutant, exerts well-documented acute and persistent CNS
      mediated effects from a variety of exposure scenarios, and so provides a useful
      case for determining whether its persistent effects can be predicted from its
      acute effects on the CNS. We recently reported that acute inhalation of toluene
      produced transcriptional effects in rat brain 18 h following a single, acute 6-h
      exposure to toluene. The goal of the present study was to determine whether these
      acute effects are also evident after long-term (sub-chronic) exposure to toluene,
      and thereby provide a mechanistic basis for predicting its persistent effects
      from short-term exposures. Male Long-Evans rats were exposed to toluene via
      inhalation (0, 10, 100, 1000 ppm, n=5/dose), 6h/day for 64 days, excluding
      weekends. The day following the final exposure, total mRNA was extracted from the
      cerebral cortex and striatum, and gene expression evaluated using Affymetrix
      arrays. Principal component analysis using all samples showed a clear
      discrimination of tissues, with striatum having more within-group variance than
      cortex. Differentially-expressed genes (DEGs) whose expression was altered by
      toluene were identified in each tissue by ANOVA followed by mapping to pathways.
      Analysis of striatum revealed 22, 57, and 94 significant DEGs for the 10 ppm, 100
      ppm, and 1000 ppm doses, respectively, far fewer than the 3352 DEGS previously
      observed after acute exposure. In addition, the direction of change in the 57
      DEGs common to both exposures differed between acute and sub-chronic exposure
      scenarios. Thus, relative to acute toluene exposure, sub-chronic exposure yielded
      both quantitative and qualitative differences in transcriptional response. Based
      on the current data, long-term gene expression changes after toluene inhalation
      cannot be readily predicted by acute responses.

PMID- 22967745
TI  - Late and early onset dementia: what is the role of vascular factors? A
      retrospective study.
AB  - BACKGROUND: Neuropathology of Alzheimer's disease (AD) demonstrates that the
      common occurrence of vascular lesions and vascular factors is suggested to
      contribute significantly to the clinical progression of the disease. This study
      has assessed the presence of vascular brain lesions and risk factors in subjects
      with diagnosis of AD and their influence on the disease course both in Late Onset
      Dementia (LOD) and in Early Onset Dementia (EOD). METHODS: MRI scans of 374 LOD
      and of 67 EOD patients were evaluated for the presence of vascular associated
      lesions and rated according to the age-related white matter changes (ARWMC) scale
      as "pure degenerative", "mixed" and "vascular" cases of dementia. Vascular risk
      factors burden (hypertension, diabetes, dyslipidemia, myocardial infarction) and
      disease progression were also assessed. RESULTS: 44% of LOD cases and 46% of EOD
      were classified as "mixed dementia cases". The vascular risk factors burden
      showed an increase from the pure degenerative to the pure vascular forms. Disease
      progression, calculated in two years using the Mini Mental State Evaluation
      (MMSE), Activities of Daily Living (ADL) and Instrumental Activities of Daily
      Living (IADL) scores, did not reveal differences among the three different
      classes of dementias. CONCLUSIONS: Vascular lesions are found in the majority of
      LOD cases and in about one half of EOD. This observation is consistent with the
      hypothesis of a synergistic effect of the degenerative and vascular factors on
      the development of cognitive dysfunction. The linear increase of the vascular
      burden supports the idea of a continuum spectrum between the pure degenerative
      and the pure vascular forms of adult-onset dementia disorders.

PMID- 22967746
TI  - Familial paroxysmal nonkinesigenic dyskinesia: clinical and genetic analysis of a
      Taiwanese family.
AB  - Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder in autosomal
      dominant inheritance. The clinical features and genetic findings of PNKD, rarely
      described in the Asians, were mostly delineated from European families. The
      present study characterized the clinical and genetic findings of a Taiwanese PNKD
      family. The clinical features of our five patients in successive three
      generations included onset age less than 10 years, attack duration between 3 min
      and 4h, and a variety of aura symptoms. The attacks were provoked not by sudden
      action but by emotional stress, caffeine, fatigue, heavy exercise and sleep
      deprivation. Sleep could abolish or diminish the attack and the attacks responded
      well to clonazepam. Sequencing the whole coding region of PNKD/MR-1 gene
      identified a heterozygous c.20 C>T (p.Ala7Val) mutation which was clearly
      segregated in the five affected patients. Comparing our patients with previously
      reported 18 families with PNKD/MR-1 mutations, the majority of the patients
      exhibited quite similar manifestations in attack patterns and precipitating
      factors. The recurrent conservative mutations in different ethnicities indicate
      importance in the pathogenesis of PNKD.

PMID- 22967747
TI  - Regional differences in cortical benzodiazepine receptors of Alzheimer, vascular,
      and mixed dementia patients.
AB  - OBJECTIVE: We examined regional benzodiazepine receptors (rBZR) using single
      photon emission CT (SPECT) in patients with Alzheimer disease (AD), vascular
      dementia (VaD), and mixed AD/VaD dementia (MD) and compared the changes in the
      availability of rBZR with those of regional cerebral blood flow (rCBF). METHODS:
      A total of 7 patients with AD, 6 with MD, and 9 with VaD underwent SPECT studies
      with N-isopropyl-p-[(123)I] iodoamphetamine and (123)I-iomazenil to measure rCBF
      and rBZR. The ratios of rCBF and rBZR uptake in brain subregions to the average
      global activity were compared among these diseases. In addition, we acquired z
      score maps using 3-dimensional stereotactic surface projections of SPECT data.
      RESULTS: Compared with AD, VaD and MD showed rCBF and rBZR reduction
      predominantly in the frontal lobe, but rBZR images revealed more extensive and
      severe defects than rCBF images. In contrast, AD showed rCBF and rBZR reduction
      predominantly in the parietotemporal lobe compared with VaD and MD, but rCBF
      images revealed more extensive defects than rBZR images. CONCLUSION: rCBF imaging
      can detect parietotemporal abnormalities in AD, while rBZR imaging may enable the
      demonstration of underlying pathophysiological differences in the frontal lobe
      between VaD, MD and AD, reflecting neuronal integrity in the cerebral cortex.

PMID- 22967748
TI  - Soluble thrombomodulin levels in plasma of multiple sclerosis patients and their
      implication.
AB  - Thrombomodulin (TM) on the cell-surface of cerebrovascular endothelial cells
      (CECs) is released into blood upon CEC damage. TM promotes activation of protein
      C (APC), an anticoagulant, anti-inflammatory, neuroprotective molecule that
      protects CECs and impedes inflammatory cell migration across the blood-brain
      barrier (BBB). Multiple sclerosis (MS) is associated with CEC damage and BBB
      dysfunction. We evaluated soluble TM (sTM) levels as a biomarker of BBB integrity
      and whether glatiramer acetate (GA) influenced sTM levels in MS patients. sTM
      levels quantified by 2-site ELISA from sera of healthy controls and systemic
      lupus erythematosus (SLE) patients (CEC-damage positive control) were compared
      with levels from patients with relapsing-remitting (RRMS) or secondary
      progressive MS (SPMS), stratified as: RRMS/GA/no relapse, RRMS/GA/in relapse,
      RRMS no GA/no relapse, RRMS/no GA/in relapse; and SPMS/no GA. Additionally,
      soluble endothelial protein C receptor (sEPCR) levels were assessed in the non
      stratified MS group, SLE patients, and controls. sTM levels were highest in RRMS
      patients taking GA with or without relapse, followed in decreasing order by SLE,
      RRMS/no GA/in relapse, SPMS, RRMS/no GA/no relapse, healthy controls. sEPCR
      levels were highest in MS patients, then SLE, then controls. sTM may be a useful
      biomarker of BBB integrity in RRMS patients. Further evaluation of sEPCR is
      needed. The finding that the highest sTM levels were in RRMS patients taking GA
      is interesting and warrants further investigation.

PMID- 22967749
TI  - Association of prion protein with cognitive functioning in humans.
AB  - OBJECTIVES: Recent animal studies have suggested a key role for cellular prion
      protein (PrPc) in the pathological consequences of amyloid plaque formation, the
      hallmark of Alzheimer's disease. This epidemiological study investigated whether
      serum concentrations of PrPc are associated with cognitive functioning in humans.
      DESIGN, SETTING, PARTICIPANTS: Cross-sectional study of 1,322 participants from
      the elderly general population in Germany, aged 65+ years at baseline (2000
      2002). MEASUREMENTS: Cognitive functioning was assessed by the COGTEL phone
      interview 5years after baseline. Serum PrPc was determined by a commercial
      immunoassay. RESULTS: In multiple linear regression adjusted for important
      confounders, subjects in higher PrPc quintiles appeared to have lower cognitive
      functioning scores than those in the lowest PrPc quintile. Spline regression
      suggested pronounced non-linearity with an inverse association between PrPc and
      cognitive functioning levelling off beyond median PrPc. Cognitive subdomain
      specific models produced somewhat heterogeneous results. CONCLUSION: The findings
      are suggestive of an independent association of PrPc with cognitive functioning
      in humans. Confirmatory and longitudinal studies are needed to elucidate the
      potential of PrPc for applications in early risk stratification for cognitive
      impairment.

PMID- 22967750
TI  - Development of brucine-loaded microsphere/thermally responsive hydrogel
      combination system for intra-articular administration.
AB  - Intra-articular drug delivery system could directly deliver a drug to an affected
      joint and offer the possibility of reaching high drug concentrations at the site
      of action with limited systemic toxicity. However, depending on their chemical
      structure, some active compounds were rapidly cleared from the joint, thus
      requiring numerous injections, which could cause infection or joint disability.
      To control the release behavior for prolonged time periods, a novel biologically
      based drug delivery vehicle was designed for intra-articular using
      microsphere/thermally responsive hydrogel combination system in this paper. And
      brucine was the test drug. The system was constructed by dispersing the brucine
      microspheres which was prepared by using a spray-drying method in a thermally
      responsive biopolymer hydrogel contained with chitosan-glycerol-borax. The
      microspheres were spherical as evidenced by the scanning electron microscopy
      (SEM) photographs. And the entrapment rate was 98.60% w/w with an average size
      range of 0.9-4.5 MUm. Fourier transforms infrared (FT-IR) spectroscopy and X-ray
      diffraction (XRD) revealed the absence of drug-polymer interaction and amorphous
      nature of an entrapped drug. From the in vitro drug release study we could see
      that there was a burst release of microsphere, which was obviously retarded when
      dispersed in hydrogel. And the studies of biocompatibility with synovium showed
      that no apparent thickening or hyperplasia of the synovium, a small quality of
      phlogocyte imbibitions was observed. The results of FX imaging in rats showed
      that by intra-articular injection the BMH could stay in articular for over 7 days
      were consistent with our in vitro release. And the results of pharmacodynamics
      revealed the BMH could benefit OA joint by suppressing the levels of TNF-alpha
      and IL-1beta, protect the damaged joint from degradation. The novel
      microsphere/thermoresponsive hydrogel combination system could be a promising
      treatment option for OA and RA. In conclusion, the system appears to be generally
      biocompatible with synovium and could control the drug release for several days;
      hence it might be suitable for the development of treatment strategies for
      rheumatic diseases.

PMID- 22967752
TI  - Low levels of vitamin D are common in patients with ileal pouches irrespective of
      pouch inflammation.
AB  - BACKGROUND: Vitamin D (25(OH) D3) levels in pouch patients are not well defined.
      AIM: To evaluate the frequency and factors associated with low 25(OH) D3 levels
      in pouch patients with underlying inflammatory bowel disease (IBD). METHODS: A
      consecutive of 157 pouch patients was identified from our Pouchitis Registry. A
      sample of 155 ulcerative colitis (UC) patients without IPAA served as controls.
      RESULTS: The mean age of the cohort was 37.5 +/- 14.2 years, with 86 (54.8%)
      being female. Low 25(OH)D3 levels (<31 ng/mL) were detected in 69.4% of patients
      (N=109). 34 (21.7%) of the 157 patients examined were 25(OH)D3 deficient (<20
      ng/mL). This was higher than the frequency of vitamin D insufficiency or
      deficiency in a sample of UC patients without IPAA. Between patients with and
      without normal 25(OH) D3 levels (>31 ng/mL), no differences were identified in
      terms of demographic, pouch, and medication variables. A low hemoglobin level was
      found to be associated with low 25(OH) D3 levels in both univariate (p=0.02) and
      multivariate analyses (odds ratio [OR]=3.37; 95% confidence interval [CI]: 1.41
      8.06; p=0.01). Low levels of 25(OH)D3 was not related to markers of pouch
      inflammation, in particular there was no relation to pouchitis (OR=1.20; 95% CI:
      0.41-3.52; p=0.74). CONCLUSION: Low 25(OH)D3 level was common in this cohort,
      irrespective of inflammation of the pouch, possibly suggesting a strategy of
      routine testing in this population. Anemia was found to be associated with a low
      25(OH)D3 level.

PMID- 22967751
TI  - Proliferative cell nuclear antigen (PCNA) expression in the intestine of Salmo
      trutta trutta naturally infected with an acanthocephalan.
AB  - BACKGROUND: Changes in the production of proliferating cell nuclear antigen
      (PCNA), a 36 kd protein involved in protein synthesis, within intestinal
      epithelia can provide an early indication of deviations to normal functioning.
      Inhibition or stimulation of cell proliferation and PCNA can be determined
      through immunohistochemical staining of intestinal tissue. Changes in the
      expression of PCNA act as an early warning system of changes to the gut and this
      application has not been applied to the fields of aquatic parasitology and fish
      health. The current study set out to determine whether a population of wild brown
      trout, Salmo trutta trutta (L.) harbouring an infection of the acanthocephalan
      Dentitruncus truttae Sinzar, 1955 collected from Lake Piediluco in Central Italy
      also effected changes in the expression of PCNA. METHODS: A total of 29 brown
      trout were investigated, 19 of which (i.e. 65.5%) were found to harbour
      acanthocephalans (5-320 worms fish-1). Histological sections of both uninfected
      and infected intestinal material were immunostained for PCNA. RESULTS: The
      expression of PCNA was observed in the epithelial cells in the intestinal crypts
      and within the mast cells and fibroblasts in the submucosa layer which is
      consistent with its role in cell proliferation and DNA synthesis. The number of
      PCNA-positive cells in both the intestinal epithelium and the submucosa layer in
      regions close to the point of parasite attachment were significantly higher than
      the number observed in uninfected individuals and in infected individuals in
      zones at least 0.7 cm from the point of parasite attachment (ANOVA, p < 0.05).
      CONCLUSIONS: An infection of the acanthocephalan D. truttae within the intestinal
      tract of S. t. trutta effected a significant increase in the number of PCNA
      positive cells (mast cells and fibroblasts) at the site of parasite attachment
      when compared to the number of positive cells found in uninfected conspecifics
      and in tissue zones away from the point of parasite attachment.

PMID- 22967754
TI  - Eccentric hip abductor weakness in patients with symptomatic external snapping
      hip.
AB  - Symptomatic external snapping hip can be a long-standing condition affecting
      physical function in younger people between 15-40 years. Gluteal weakness has
      been suggested to be associated with the condition. The aim of this study was to
      investigate whether eccentric hip abduction strength is decreased in patients
      with external snapping hip compared with healthy matched controls, and to examine
      isometric hip abduction, adduction, extension, flexion, internal rotation, and
      external rotation in patients with external snapping hip and matched controls.
      Thirteen patients with external snapping hip were compared with 13 healthy
      matched controls in a cross-sectional study design. The mean age of the patients
      was 25.5 +/- 3.4 years and the mean age of the controls was 25.6 +/- 2.6 years.
      Eccentric and isometric strength were assessed with a handheld dynamometer, using
      reliable test procedures. Eccentric hip abduction strength was 16% lower in
      patients with external snapping hip compared with healthy matched controls (1.50
      +/- 0.47 Nm/kg versus 1.82 +/- 0.48 Nm/kg, P = 0.01). No other strength
      differences were measured between patients and controls (P > 0.05). Eccentric hip
      abductor weakness was present in patients with symptomatic external snapping hip
      compared with healthy matched controls.

PMID- 22967753
TI  - Genetic variation of Gongylonema pulchrum from wild animals and cattle in Japan
      based on ribosomal RNA and mitochondrial cytochrome c oxidase subunit I genes.
AB  - The gullet worm (Gongylonema pulchrum) has been recorded from a variety of
      mammals worldwide, including monkeys and humans. Due to its wide host range, it
      has been suggested that the worm may be transmitted locally to any mammalian host
      by chance. To investigate this notion, the ribosomal RNA gene (rDNA), mainly
      regions of the internal transcribed spacers (ITS) 1 and 2, and a cytochrome c
      oxidase subunit I (COI) region of mitochondrial DNA of G. pulchrum were
      characterized using parasites from the following hosts located in Japan: cattle,
      sika deer, wild boars, Japanese macaques, a feral Reeves's muntjac and captive
      squirrel monkeys. The rDNA nucleotide sequences of G. pulchrum were generally
      well conserved regardless of their host origin. However, a few
      insertions/deletions of nucleotides along with a few base substitutions in the
      ITS1 and ITS2 regions were observed in G. pulchrum from sika deer, wild boars and
      Japanese macaques, and those differed from G. pulchrum in cattle, the feral
      Reeves's muntjac and captive squirrel monkeys. The COI sequences of G. pulchrum
      were further divided into multiple haplotypes and two groups of haplotypes, i.e.
      those from a majority of sika deer, wild boars and Japanese macaques and those
      from cattle and zoo animals, were clearly differentiated. Our findings indicate
      that domestic and sylvatic transmission cycles of the gullet worm are currently
      present, at least in Japan. 

PMID- 22967755
TI  - Transcriptomic profiling of the reproductive mode switch in the pea aphid in
      response to natural autumnal photoperiod.
AB  - Aphids are among the rare organisms that can change their reproductive mode
      across their life cycle. During spring and summer they reproduce clonally and
      efficiently by parthenogenesis. At the end of summer aphids perceive the
      shortening of day length which triggers the production of sexual individuals -
      males and oviparous females - that will mate and lay overwintering cold-resistant
      eggs. Recent large scale transcriptomic studies allowed the discovery of
      transcripts and functions such as nervous and hormonal signaling involved in the
      early steps of detection and transduction of the photoperiodic signal.
      Nevertheless these experiments were performed under controlled conditions when
      the photoperiod was the only varying parameter. To characterize the response of
      aphids under natural conditions, aphids were reared outdoor both in summer and
      autumn and material was collected to compare their transcriptomic profile using a
      cDNA microarray containing around 7000 transcripts. Statistical analyses revealed
      that close to 5% of these transcripts (367) were differentially expressed at two
      developmental stages of the process in response to the autumnal environmental
      conditions. Functional classification of regulated transcripts confirmed the
      putative contribution of the neuro-endocrine system in the process. Furthermore,
      these experiments revealed the regulation of transcripts involved in juvenile
      hormone synthesis and signaling pathway, confirming the key role played by these
      molecules in the reproductive mode switch. Aphids placed under outdoor conditions
      were confronted to a range of abiotic factors such as temperature fluctuations
      which was confirmed by the differential expression of an important proportion of
      heat shock protein transcripts between the two seasons. Finally, this original
      approach completed the understanding of genetic programs involved in aphid
      phenotypic plasticity.

PMID- 22967757
TI  - Hematopoietic stem cell niche: an interplay among a repertoire of multiple
      functional niches.
AB  - BACKGROUND: Hematopoietic stem cell (HSC) niche of the BM provides a specialized
      microenvironment for the regulation of HSCs. The strict control of HSCs by the
      niche coordinates the balance between the proliferation and the differentiation
      of HSCs for the homeostasis of the blood system in steady states and during
      stress hematopoiesis. The osteoblastic and vascular niches are the classically
      identified constituents of the BM niche. SCOPE OF REVIEW: Recent research
      broadens our understanding of the BM niche as an assembly of multiple niche cells
      within the BM. We provide an overview of the HSC niche aiming to delineate the
      defined and possible niche cell interactions which collectively modulate the HSC
      integrity. MAJOR CONCLUSIONS: Multiple cells in the BM, including osteoblasts,
      vascular endothelia, perivascular mesenchymal cells and HSC progeny cells,
      function conjunctively as niche cells to regulate HSCs. GENERAL SIGNIFICANCE: The
      study of HSC niche cells and their functions provides insights into stem cell
      biology and also may be extrapolated into the study of cancer stem cells. This
      article is part of a Special Issue entitled Biochemistry of Stem Cells.

PMID- 22967756
TI  - Learning curves, taking instructions, and patient safety: using a theoretical
      domains framework in an interview study to investigate prescribing errors among
      trainee doctors.
AB  - BACKGROUND: Prescribing errors are a major source of morbidity and mortality and
      represent a significant patient safety concern. Evidence suggests that trainee
      doctors are responsible for most prescribing errors. Understanding the factors
      that influence prescribing behavior may lead to effective interventions to reduce
      errors. Existing investigations of prescribing errors have been based on Human
      Error Theory but not on other relevant behavioral theories. The aim of this study
      was to apply a broad theory-based approach using the Theoretical Domains
      Framework (TDF) to investigate prescribing in the hospital context among a sample
      of trainee doctors. METHOD: Semistructured interviews, based on 12 theoretical
      domains, were conducted with 22 trainee doctors to explore views, opinions, and
      experiences of prescribing and prescribing errors. Content analysis was
      conducted, followed by applying relevance criteria and a novel stage of critical
      appraisal, to identify which theoretical domains could be targeted in
      interventions to improve prescribing. RESULTS: Seven theoretical domains met the
      criteria of relevance: "social professional role and identity," "environmental
      context and resources," "social influences," "knowledge," "skills," "memory,
      attention, and decision making," and "behavioral regulation." From critical
      appraisal of the interview data, "beliefs about consequences" and "beliefs about
      capabilities" were also identified as potentially important domains.
      Interrelationships between domains were evident. Additionally, the data supported
      theoretical elaboration of the domain behavioral regulation. CONCLUSIONS: In this
      investigation of hospital-based prescribing, participants' attributions about
      causes of errors were used to identify domains that could be targeted in
      interventions to improve prescribing. In a departure from previous TDF practice,
      critical appraisal was used to identify additional domains that should also be
      targeted, despite participants' perceptions that they were not relevant to
      prescribing errors. These were beliefs about consequences and beliefs about
      capabilities. Specifically, in the light of the documented high error rate,
      beliefs that prescribing errors were not likely to have consequences for patients
      and that trainee doctors are capable of prescribing without error should also be
      targeted in an intervention. This study is the first to suggest critical
      appraisal for domain identification and to use interview data to propose
      theoretical elaborations and interrelationships between domains.

PMID- 22967758
TI  - Synergistic effect of conjugated linolenic acid isomers against induced oxidative
      stress, inflammation and erythrocyte membrane disintegrity in rat model.
AB  - BACKGROUND: alpha-Eleostearic acid and punicic acid, two typical conjugated
      linolenic acid (CLnA) isomers present in bitter gourd and snake gourd oil
      respectively, exhibit contrasting cis-trans configuration which made them
      biologically important. METHODS: Rats were divided into six groups. Group 1 was
      control and group 2 was treated control. Rats in the groups 3 and 4 were treated
      with mixture of alpha-eleostearic acid and punicic acid (1:1) (0.5% and 1.0%
      respectively) while rats in the groups 5 and 6 were treated with 0.5% of alpha
      eleostearic acid and 0.5% of punicic acid respectively along with sodium arsenite
      by oral gavage once per day. RESULTS: Results showed that increase in nitric
      oxide synthase (NOS) activity, inflammatory markers expression, platelet
      aggregation, lipid peroxidation, protein oxidation, DNA damage and altered
      expression of liver X receptor-alpha (LXR-alpha) after arsenite treatment were
      restored with the supplementation of oils containing CLnA isomers. Altered
      activities of different antioxidant enzymes such as superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase and ferric reducing
      ability of plasma (FRAP) also restored after oil supplementation. Altered
      morphology and fluidity of erythrocyte membrane studied by atomic force and
      scanning electron microscopy, after stress induction were significantly improved
      due to amelioration in cholesterol/phospholipid ratio and fatty acid profile of
      membrane. Oils treatment also improved morphology of liver and fatty acid
      composition of hepatic lipid. CONCLUSIONS: Overall two isomers showed synergistic
      antioxidant and anti-inflammatory effect against induced perturbations and
      membrane disintegrity. GENERAL SIGNIFICANCE: Synergistic antioxidant and anti
      inflammatory role of these CLnA isomers were established by this study.

PMID- 22967759
TI  - Entamoeba histolytica thioredoxin reductase: molecular and functional
      characterization of its atypical properties.
AB  - BACKGROUND: Entamoeba histolytica, an intestinal protozoan that is the causative
      agent of amoebiasis, is exposed to elevated amounts of highly toxic reactive
      oxygen and nitrogen species during tissue invasion. Thioredoxin reductase
      catalyzes the reversible transfer of reducing equivalents between NADPH and
      thioredoxin, a small protein that plays key metabolic functions in maintaining
      the intracellular redox balance. METHODS: The present work deals with in vitro
      steady state kinetic studies aimed to reach a better understanding of the kinetic
      and structural properties of thioredoxin reductase from E. histolytica (EhTRXR).
      RESULTS: Our results support that native EhTRXR is a homodimeric covalent protein
      that is able to catalyze the NAD(P)H-dependent reduction of amoebic thioredoxins
      and S-nitrosothiols. In addition, the enzyme exhibited NAD(P)H dependent oxidase
      activity, which generates hydrogen peroxide from molecular oxygen. The enzyme can
      reduce compounds like methylene blue, quinones, ferricyanide or nitro
      derivatives; all alternative substrates displaying a relative high capacity to
      inhibit disulfide reductase activity of EhTRXR. CONCLUSIONS AND GENERAL
      SIGNIFICANCE: Interestingly, EhTRXR exhibited kinetic and structural properties
      that differ from other low molecular weight TRXR. The TRX system could play an
      important role in the parasite defense against reactive species. The latter
      should be critical during the extra intestinal phase of the amoebic infection. So
      far we know, this is the first in depth characterization of EhTRXR activity and
      functionality.

PMID- 22967760
TI  - The TGFbeta superfamily in stem cell biology and early mammalian embryonic
      development.
AB  - BACKGROUND: Members of the Transforming Growth Factor-beta (TGFbeta) superfamily
      of cytokines are essential for early embryonic development and play crucial roles
      in pluripotency and differentiation of embryonic stem cells in vitro. SCOPE OF
      REVIEW: In this review, we discuss how TGFbeta family signals are read by cells
      and how they are modulated by the cellular context. Furthermore, we review recent
      advances in our understanding of TGFbeta function in embryonic stem cells and
      point out hot topics at the intersection of TGFbeta signaling and stem cell
      biology fields. MAJOR CONCLUSION: TGFbeta family signals are essential for early
      mammalian development and the importance of this pathway is reflected in
      pluripotent stem cells derived from the mammalian embryo. GENERAL SIGNIFICANCE:
      Understanding signaling pathways underlying pluripotency and cell fate
      specification holds promises for the advent of personalized regenerative
      medicine. This article is part of a Special Issue entitled Biochemistry of Stem
      Cells.

PMID- 22967762
TI  - Characterization of O-GlcNAc cycling and proteomic identification of
      differentially O-GlcNAcylated proteins during G1/S transition.
AB  - BACKGROUND: DNA replication represents a critical step of the cell cycle which
      requires highly controlled and ordered regulatory mechanisms to ensure the
      integrity of genome duplication. Among a plethora of elements, post-translational
      modifications (PTMs) ensure the spatiotemporal regulation of pivotal proteins
      orchestrating cell division. Despite increasing evidences showing that O
      GlcNAcylation regulates mitotic events, the impact of this PTM in the early steps
      of the cell cycle remains poorly understood. METHODS AND RESULTS: Quiescent MCF7
      cells were stimulated by serum mitogens and cell cycle progression was determined
      by flow cytometry. The levels of O-GlcNAc modified proteins, O-GlcNAc Transferase
      (OGT) and O-GlcNAcase (OGA) were examined by Western blotting and OGA activity
      was measured during the progression of cells towards S phase. A global decrease
      in O-GlcNAcylation was observed at S phase entry, concomitantly to an increase in
      the activity of OGA. A combination of two-dimensional electrophoresis, Western
      blotting and mass spectrometry was then used to detect and identify cell cycle
      dependent putative O-GlcNAcylated proteins. 58 cytoplasmic and nuclear proteins
      differentially O-GlcNAcylated through G1/S transition were identified and the O
      GlcNAc variations of Cytokeratin 8, hnRNP K, Caprin-1, Minichromosome Maintenance
      proteins MCM3, MCM6 and MCM7 were validated by immunoprecipitation. CONCLUSIONS:
      The dynamics of O-GlcNAc is regulated during G1/S transition and observed on key
      proteins involved in the cytoskeleton networks, mRNA processing, translation,
      protein folding and DNA replication. GENERAL SIGNIFICANCE: Our results led us to
      propose that O-GlcNAcylation joins the PTMs that take part in the regulation of
      DNA replication initiation.

PMID- 22967763
TI  - Signaling pathways regulating innate immune responses in shrimp.
AB  - The first line of defense against microbial infections in animals is innate
      immune response which triggers diverse humoral and cellular activities via signal
      transduction pathways. Toll, IMD and JAK/STAT pathways are regarded as the main
      pathways regulating the immune response of invertebrates. This paper reviews the
      main progress of the investigation on the immune response to pathogen's infection
      in shrimp and supposes that these three signal pathways exist in shrimp. Most of
      the components (proteins or genes) involved in Toll pathway of Drosophila have
      been cloned also in shrimp which suggested the existence of Toll pathway in
      shrimp. The data update shows that the Toll pathway of shrimp is responsive not
      only to Gram-positive bacteria, Gram-negative bacteria, but also to WSSV.
      Challenge of WSSV can lead to the variation of transcription level of all
      identified components in shrimp Toll pathway, which supported that Toll pathway
      in shrimp played important roles during WSSV infection. Two major homologs to the
      components of IMD pathway of Drosophila, IMD and Relish, have been identified in
      shrimp, which indicated that IMD pathway should be existed in shrimp and might
      play important roles in regulating the immune response of shrimp to bacteria and
      virus infection. Relish in IMD pathway and dorsal in Toll pathway of shrimp were
      both involved in the immune response of shrimp to bacteria and virus infection,
      which implied that these two pathways are not completely separated during the
      immune response of shrimp. The transcription of STAT in shrimp was modulated
      after WSSV infection, which suggested that a putative JAK/STAT pathway might
      exist in shrimp and be very important to virus infection. Study on the signaling
      pathway regulating the immune response in shrimp could help us to understand the
      innate immune system, and would provide instructions to shrimp disease control.
      Obviously, to get more clear ideas about the innate immunological pathways in
      shrimp, more solid functional studies should be done in the future.

PMID- 22967761
TI  - Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid
      hormone signaling.
AB  - BACKGROUND: Thyroid hormone signaling is critical for development, growth and
      metabolic control in vertebrates. Although serum concentration of thyroid hormone
      is remarkable stable, deiodinases modulate thyroid hormone signaling on a time-
      and cell-specific fashion by controlling the activation and inactivation of
      thyroid hormone. SCOPE OF THE REVIEW: This review covers the recent advances in
      D2 biology, a member of the iodothyronine deiodinase family, thioredoxin fold
      containing selenoenzymes that modify thyroid hormone signaling in a time- and
      cell-specific manner. MAJOR CONCLUSIONS: D2-catalyzed T3 production increases
      thyroid hormone signaling whereas blocking D2 activity or disruption of the Dio2
      gene leads to a state of localized hypothyroidism. D2 expression is regulated by
      different developmental, metabolic or environmental cues such as the hedgehog
      pathway, the adrenergic- and the TGR5-activated cAMP pathway, by xenobiotic
      molecules such as flavonols and by stress in the endoplasmic reticulum, which
      specifically reduces de novo synthesis of D2 via an eIF2a-mediated mechanism.
      Thus, D2 plays a central role in important physiological processes such as
      determining T3 content in developing tissues and in the adult brain, and
      promoting adaptive thermogenesis in brown adipose tissue. Notably, D2 is critical
      in the T4-mediated negative feed-back at the pituitary and hypothalamic levels,
      whereby T4 inhibits TSH and TRH expression, respectively. Notably, ubiquitination
      is a major step in the control of D2 activity, whereby T4 binding to and/or T4
      catalysis triggers D2 inactivation by ubiquitination that is mediated by the E3
      ubiquitin ligases WSB-1 and/or TEB4. Ubiquitinated D2 can be either targeted to
      proteasomal degradation or reactivated by deubiquitination, a process that is
      mediated by the deubiquitinases USP20/33 and is important in adaptive
      thermogenesis. GENERAL SIGNIFICANCE: Here we review the recent advances in the
      understanding of D2 biology focusing on the mechanisms that regulate its
      expression and their biological significance in metabolically relevant tissues.
      This article is part of a Special Issue entitled Thyroid hormone signalling.

PMID- 22967764
TI  - Synthesis of quinoline derivatives for fluorescent imaging certain bacteria.
AB  - Highly fluorescent quinoline derivatives were synthesized using Sc(OTf)(3)
      catalyzed imino Diels-Alder reaction. Both the aromatic and their analogous
      tetradehydroquinoline derivatives were explored for the detection of bacteria
      using fluorescent imaging studies. Surprisingly the aromatic quinoline
      derivatives show a remarkable fluorescent response that can be useful in the
      detection of both gram positive and gram negative bacteria even at a
      concentration in the range of 0.078 mM.

PMID- 22967766
TI  - Induced production of mycotoxins in an endophytic fungus from the medicinal plant
      Datura stramonium L.
AB  - Epigenetic modifiers, including DNA methyltransferase (DNMT) or histone
      deacetylase (HDAC) inhibitors, are useful to induce the expression of otherwise
      dormant biosynthetic genes under standard laboratory conditions. We isolated
      several endophytic fungi from the medicinal plant Datura stramonium L., which
      produces pharmaceutically important tropane alkaloids, including scopolamine and
      hyoscyamine. Although none of the endophytic fungi produced the tropane
      alkaloids, supplementation of a DNMT inhibitor, 5-azacytidine, and/or a HDAC
      inhibitor, suberoylanilide hydroxamic acid, to the culture medium induced the
      production of mycotoxins, including alternariol, alternariol-5-O-methyl ether, 3'
      hydroxyalternariol-5-O-methyl ether, altenusin, tenuazonic acid, and altertoxin
      II, by the endophytic fungus Alternaria sp. This is the first report of a
      mycotoxin-producing endophytic fungus from the medicinal plant D. stramonium L.
      This work demonstrates that treatments with epigenetic modifiers induce the
      production of mycotoxins, thus providing a useful tool to explore the
      biosynthetic potential of the microorganisms.

PMID- 22967765
TI  - Synthesis and evaluation of novel 1,3,4-oxadiazole derivatives of marine
      bromopyrrole alkaloids as antimicrobial agent.
AB  - In an attempt to identify new potential lead as antimicrobial agent, twenty
      hybrids of marine bromopyrrole alkaloids with 1,3,4-oxadiazole were designed
      based on molecular hybridization technique and synthesized. Synthesized molecules
      were evaluated for their antibacterial, antifungal and antitubercular activities.
      Hybrids 5d, 5i, 5j and 5k exhibited equivalent antibacterial activity (MIC of
      1.56 MUg/mL) compared with standard drug ciprofloxacin against Staphylococcus
      aureus and Escherichia coli. Equal antifungal activity (MIC of 1.56 MUg/mL) was
      shown by of hybrids 5j, 5k and 7d compared with standard Amphotericin-B. The
      inhibition of Mycobacterium tuberculosis at concentrations as low as 1.6 and 1.5
      MUg/mL by compounds 5f and 7d respectively indicates that these compounds can act
      as leads for development of newer anti-TB compounds.

PMID- 22967768
TI  - Cardiac transapical approach: a new solution for the treatment of complex
      thoracic aortic disease.

PMID- 22967767
TI  - Allylic thiocyanates as a new class of antitubercular agents.
AB  - TB is a global public health emergency in which new drugs are desperately needed.
      Herein we report on the synthesis of a diverse panel of 41 aryl allylic azides,
      thiocyanates, isothiouronium salts, and N,N'-diacetylisothioureas that were
      evaluated for their in vitro activity against replicating and non-replicating
      Mycobacterium tuberculosis (Mtb) H(37)Rv and toxicity to VERO cells. We found a
      selective group of new and promising compounds having good (micromolar) to
      excellent (sub-micromolar) potency against replicating Mtb H(37)Rv. Allylic
      thiocyanates bearing halophenyl (halo=2-Br, 4-Br, 4-Cl, 4-F), 4-methylphenyl and
      2-naphthyl moieties were the most active as antitubercular agents. In particular,
      the 2-bromophenyl-substituted thiocyanate showed MIC=0.25 MUM against replicating
      Mtb, MIC=8.0 MUM against non-replicating Mtb and IC(50)=32 MUM in the VERO
      cellular toxicity assay.

PMID- 22967769
TI  - Discussion.

PMID- 22967770
TI  - Selective antegrade cerebral perfusion and mild (28 degrees C-30 degrees C)
      systemic hypothermic circulatory arrest for aortic arch replacement: results from
      1002 patients.
AB  - OBJECTIVES: The use of selective antegrade cerebral perfusion (ACP) makes deep
      hypothermia nonessential for aortic arch replacement. Consequently, a growing
      tendency to increase the body temperature during circulatory arrest with ACP has
      recently been reported from various institutions. However, very little is known
      about the clinical effect of different modes of ACP (unilateral vs bilateral) on
      neurologic morbidity. Also, the safe limits of this approach for spinal chord and
      visceral organ protection are yet to be defined. METHODS: Between January 2000
      and January 2011, 1002 consecutive patients underwent aortic arch repair during
      ACP (unilateral, 673; bilateral, 329) with mild systemic hypothermia (30 degrees
      C +/- 2 degrees C; range, 26 degrees -34 degrees C) at 2 centers in Germany. The
      mean patient age was 62 +/- 14 years, 663 patients (66%) were men, and 347
      patients (35%) had acute type A dissection. Hemiarch replacement was performed in
      684 patients (68%), and 318 (32%) underwent total arch replacement. RESULTS: The
      cardiopulmonary bypass time accounted for 158 +/- 56 minutes and the myocardial
      ischemic time, 101 +/- 41 minutes. Isolated ACP was performed for 36 +/- 19
      minutes (range, 9-135). We observed new postoperative permanent neurologic
      deficits in 28 patients (3%; stroke in 25 and paraplegia in 3) and transient
      neurologic deficits in 42 patients (4%). All 3 cases of paraplegia occurred in
      patients with acute type A dissection and a broad range of ACP times (24, 41, and
      127 minutes). A trend was seen toward a reduced permanent neurologic deficit rate
      after unilateral ACP (P = .06), but no difference was seen in the occurrence of
      transient neurologic deficits (P = .6). Overall, the early mortality rate was 5%
      (n = 52). Temporary dialysis was necessary primarily after surgery in 38 patients
      (4%). When corrected for the unequal distribution of type A dissection,
      neurologic morbidity, early mortality, and the need for temporary dialysis were
      independent of the duration of ACP and were not affected by unilateral versus
      bilateral ACP. CONCLUSIONS: Current data suggest that ACP and mild systemic
      hypothermic circulatory arrest can be safely applied to complex aortic arch
      surgery even in a subgroup of patients with up to 90 minutes of ACP. Unilateral
      ACP offers at least equal brain and visceral organ protection as bilateral ACP
      and might be advantageous in that it reduces the incidence of embolism arising
      from surgical manipulation on the arch vessels.

PMID- 22967771
TI  - Delayed presentation of aortic laceration from seventh rib fracture: an uncommon
      complication.

PMID- 22967772
TI  - Pharmacogenomic associations with weight gain in olanzapine treatment of patients
      without schizophrenia.
AB  - OBJECTIVE: Pharmacogenomic analyses of weight gain during treatment with second
      generation antipsychotics have resulted in a number of associations with variants
      in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor
      (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed
      subjects with schizophrenia who had prior antipsychotic exposure that may have
      influenced the amount of weight gained from subsequent therapies. We assessed the
      relationships between single-nucleotide polymorphisms (SNPs) in these genes with
      weight gain during treatment with olanzapine in a predominantly antipsychotic
      naive population. METHOD: The association between 5 ANKK1, 54 DRD2, and 11 HTR2C
      SNPs and weight change during 8 weeks of olanzapine treatment was assessed in 4
      pooled studies of 205 white patients with diagnoses other than schizophrenia who
      were generally likely to have had limited previous antipsychotic exposure.
      RESULTS: The A allele of DRD2 rs2440390(A/G) was associated with greater weight
      gain in the entire study sample (P = .0473). Three HTR2C SNPs in strong linkage
      disequilibrium, rs6318, rs2497538, and rs1414334, were associated with greater
      weight gain in women but not in men (P = .0032, .0012, and .0031, respectively).
      A significant association with weight gain for 2 HTR2C SNPs previously reported
      associated with weight gain, -759C/T (rs3813929) and -697G/C (rs518147), was not
      found. CONCLUSIONS: Associations between weight gain and HTR2C and DRD2 variants
      in whites newly exposed to olanzapine may present opportunities for the
      individualization of medication selection and development based on differences in
      adverse events observed across genotype groups.

PMID- 22967773
TI  - Risk of injurious road traffic crash after prescription of antidepressants.
AB  - OBJECTIVE: To estimate the risk of road traffic crash associated with
      prescription of antidepressants. METHOD: Data were extracted and matched from 3
      French national databases: the national health care insurance database, police
      reports, and the national police database of injurious crashes. A case-control
      analysis comparing 34,896 responsible versus 37,789 nonresponsible drivers was
      conducted. Case-crossover analysis was performed to investigate the acute effect
      of medicine exposure. RESULTS: 72,685 drivers, identified by their national
      health care number, involved in an injurious crash in France from July 2005 to
      May 2008 were included. 2,936 drivers (4.0%) were exposed to at least 1
      antidepressant on the day of the crash. The results showed a significant
      association between the risk of being responsible for a crash and prescription of
      antidepressants (odds ratio [OR] = 1.34; 95% CI, 1.22-1.47). The case-crossover
      analysis showed no association with treatment prescription, but the risk of road
      traffic crash increased after an initiation of antidepressant treatment (OR =
      1.49; 95% CI, 1.24-1.79) and after a change in antidepressant treatment (OR =
      1.32; 95% CI, 1.09-1.60). CONCLUSIONS: Patients and prescribers should be warned
      about the risk of crash during periods of treatment with antidepressant
      medication and about particularly high vulnerability periods such as those when a
      treatment is initiated or modified.

PMID- 22967774
TI  - "Bath salts"-induced psychosis and serotonin toxicity.

PMID- 22967775
TI  - "Bath salts" and the return of serotonin syndrome.

PMID- 22967777
TI  - Can women have it all? Psychiatry and the gender gap.

PMID- 22967776
TI  - Interferon-induced depression in chronic hepatitis C: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To carry out a systematic review of the risk factors for, and
      incidence of, major depressive episode (MDE) related to antiviral therapy for
      chronic hepatitis C. DATA SOURCES: The MEDLINE, PsycINFO, and Cochrane databases
      were searched to locate articles published from the earliest available online
      year until June 2011 using the keywords hepatitis C, interferon-alpha,
      peginterferon, pegylated interferon, depression, and mood and Boolean operators.
      Articles written in English, Spanish, and French were included. STUDY SELECTION:
      Prospective studies reporting incidence of interferon-alpha-induced MDE were
      included. At baseline, patients did not present a DSM-IV/ICD depressive episode,
      and evaluation was performed by a trained clinician. Twenty-six observational
      studies met the inclusion criteria. DATA EXTRACTION: Extracted data included
      authors, year of publication, design, characteristics of the population, viral
      coinfection, adjunctive psychopharmacology, instruments to assess depression,
      dose and type of interferon-alpha, adjunctive ribavirin treatment, and follow-up
      time. Outcome of incidence of MDE (primary outcome measure) was abstracted, as
      were potential predictive variables. DATA SYNTHESIS: A full review was performed.
      Meta-analysis of the cumulative incidence of induced MDE as a function of time
      was carried out. Odds ratios (ORs) and mean differences were used to estimate the
      strength of association of variables. RESULTS: Overall cumulative incidence of
      depression was 0.25 (95% CI, 0.16 to 0.35) and 0.28 (95% CI, 0.17 to 0.42) at 24
      and 48 weeks of treatment, respectively. According to our analysis, high baseline
      levels of interleukin 6 (mean difference = 1.81; 95% CI, 1.09 to 2.52), female
      gender (OR = 1.40; 95% CI, 1.02 to 1.91), history of MDE (OR = 3.96; 95% CI, 2.52
      to 6.21), history of psychiatric disorder (OR = 3.18; 95% CI, 1.60 to 6.32),
      subthreshold depressive symptoms (mean difference = 0.96; 95% CI, 0.31 to 1.61),
      and low educational level (mean difference = -0.99; 95% CI, -1.59 to -0.39) were
      predictive variables of MDE during antiviral treatment. CONCLUSIONS: One in 4
      chronic hepatitis C patients who start interferon and ribavirin treatment will
      develop an induced major depressive episode. Clinicians should attempt a full
      evaluation of patients before starting antiviral treatment in order to identify
      those at risk of developing interferon-induced depression.

PMID- 22967778
TI  - The differential roles of trauma, posttraumatic stress disorder, and comorbid
      depressive disorders on suicidal ideation in the elderly population.
AB  - OBJECTIVE: Although depression is the strongest predictor for the full spectrum
      of suicidal ideation, several other mental disorders, eg, posttraumatic stress
      disorder (PTSD), are associated with suicidal ideation too. This study
      investigates whether suicidal ideation is specifically associated with PTSD or if
      this association is fully or partially mediated by comorbid depressive disorders.
      METHOD: A representative sample of 1,659 people aged 60-85 years from the German
      general population was examined by using self-rating instruments for PTSD,
      depression, and suicidal ideation in May and June 2008 in a cross-sectional
      study. Participants were diagnosed with PTSD when they met criteria A, B, C, and
      D for PTSD according to DSM-IV-TR. Suicidal ideation was used as the primary
      outcome measure. RESULTS: In our sample, 7.3% of subjects reported suicidal
      ideation within the last 2 weeks. Suicidal ideation was associated with a higher
      number of traumatic experiences (mean = 1.13 vs 0.78; t = -3.20; P <= .001) and
      prevalence of PTSD (12.4% vs 3.4%, chi2 = 23.39, P < .001) than in subjects
      without suicidal ideation. In logistic regression analyses including age and sex,
      traumatic experiences were associated with suicidal ideation (OR = 1.16, P =
      .011). After including PTSD in the model, this association was fully explained by
      PTSD. Moreover, PTSD was associated with suicidal ideation (OR = 3.33, P < .001),
      but after including depression in the model, the association of PTSD and suicidal
      ideation was fully mediated by depression (OR = 1.61, P < .001). CONCLUSIONS: The
      results of our study indicate that PTSD is associated with suicidal ideation, but
      this association was fully explained by comorbid depressive symptoms in the
      elderly general population. Thus, screening for depressive symptoms as well as
      administering an appropriate therapy seems the best way to prevent suicide
      attempts in the elderly, even in those patients with traumatic experiences and/or
      PTSD.

PMID- 22967780
TI  - Does varenicline worsen psychiatric symptoms in patients with schizophrenia or
      schizoaffective disorder? A review of published studies.
AB  - OBJECTIVE: To review published cases and prospective studies describing the use
      of varenicline in patients with schizophrenia and schizoaffective disorder. DATA
      SOURCES: PubMed, PsychINFO, and the Cochrane Database were searched in July 2011
      using the key words schizophrenia, schizoaffective disorder, psychosis, positive
      symptoms, negative symptoms, aggression, hostility, suicidal ideation AND
      varenicline to identify reports published between January 2006 and July 2011 in
      English. STUDY SELECTION: Five case reports, 1 case series, 1 retrospective
      study, 10 prospective studies (17 publications), and 1 meeting abstract
      describing the use of varenicline in patients with schizophrenia or
      schizoaffective disorder were identified. Review articles and articles describing
      findings other than the use of varenicline in patients with schizophrenia or
      schizoaffective disorder were excluded. Thirteen reports were included in the
      final analysis. DATA EXTRACTION: Information on each study's patient population,
      age, diagnosis, medication treatment, tobacco use history, adverse effects, and
      outcome was collected from the published reports. RESULTS: Of the 260 patients
      with schizophrenia or schizoaffective disorder who received varenicline in these
      published reports, 13 patients (5%) experienced the onset or worsening of any
      psychiatric symptom, although 3 of the 13 patients experienced a very brief
      negative effect after 1 dose. No patients experienced suicidal ideation or
      suicidal behaviors. CONCLUSIONS: Published reports suggest that, in most stable,
      closely monitored patients with schizophrenia or schizoaffective disorder,
      varenicline treatment is not associated with worsening of psychiatric symptoms.
      Current, prospective studies are assessing effectiveness and further assessing
      safety in this population.

PMID- 22967779
TI  - A cross-sectional study of plasma risperidone levels with risperidone long-acting
      injectable: implications for dopamine D2 receptor occupancy during maintenance
      treatment in schizophrenia.
AB  - OBJECTIVE: While 65%-80% occupancy of dopamine D2 receptors with antipsychotics
      has been proposed to achieve optimal therapeutic response during acute treatment
      of schizophrenia, it remains unclear as to whether it is also necessary to
      maintain D2 receptor occupancy within this "safe" window for ongoing maintenance
      treatment. The data are especially scarce for long-acting antipsychotic
      formulations. METHOD: Clinically stable patients with schizophrenia (DSM-IV)
      receiving a stable dose of risperidone long-acting injectable (LAI) as
      antipsychotic monotherapy for at least 3 months and free of any psychiatric
      hospitalization over the past 6 months were included. Dopamine D2 receptor
      occupancy levels at trough were estimated from plasma concentrations of
      risperidone plus 9-hydroxyrisperidone immediately before the intramuscular
      injection of risperidone LAI, using a 1-site binding model derived from our
      previous positron emission tomography data. This study was conducted from October
      to December 2011. RESULTS: 36 patients were included in this study (mean +/- SD
      age, 49.3 +/- 14.0 years; mean +/- SD dose and interval of injections, 38.2 +/-
      11.6 mg and 16.5 +/- 14.0 days, respectively). Mean +/- SD D2 receptor occupancy
      was 62.1% +/- 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an
      occupancy of >= 65%. On the other hand, 13.9% (n = 5) showed a D2 occupancy as
      high as over 80% at the estimated trough. CONCLUSIONS: More than half of patients
      taking risperidone LAI maintained clinical stability without achieving continuous
      blockade of dopamine D2 receptors >= 65% in real-world clinical settings. Results
      suggest that sustained dopamine D2 receptor occupancy levels of >= 65% may not be
      necessary for maintenance treatment with risperidone LAI in schizophrenia.

PMID- 22967781
TI  - Predictors of long-term return to work and symptom remission in sick-listed
      patients with major depression.
AB  - OBJECTIVE: Although major depressive disorder (MDD) has substantial negative
      effects on work outcomes, little is known regarding how to promote a return to
      work (RTW) after MDD-related sickness absence. The present study aimed to examine
      predictors across multiple domains for long-term RTW in patients who are sick
      listed because of their MDD, and to compare these with predictors for long-term
      symptom remission. METHOD: Participants (n = 117) were diagnosed with MDD
      according to DSM-IV criteria, absent from work for at least 25% of their contract
      hours, and referred by occupational physicians to outpatient treatment. Long-term
      full RTW (working the full number of contract hours for at least 4 weeks) and
      long-term symptom remission (Hamilton Depression Rating Scale score <= 7) were
      examined during the 18-month follow-up. Potential predictors (diagnostic,
      sociodemographic, personality, and work-related) were assessed at baseline. Data
      were collected from December 2007 to March 2011. RESULTS: Stepwise logistic
      regression analyses with backward elimination (P <= .05) resulted in a final
      prediction model including depression severity (odds ratio [OR] = 0.92; 95% CI,
      0.87-0.97; P = .003), comorbid anxiety (OR = 0.21; 95% CI, 0.05-0.84; P = .028),
      work motivation (OR = 1.87; 95% CI, 1.18-2.96; P = .008), and conscientiousness
      (OR = 1.10; 95% CI, 1.02-1.18; P = .012) as predictors of long-term RTW. Long
      term symptom remission was only predicted by depression severity (OR = 0.93; 95%
      CI, 0.89-0.98; P = .005). CONCLUSIONS: Whereas long-term symptom remission is
      only predicted by diagnostic factors, long-term RTW is also predicted by personal
      and work-related factors. These findings provide suggestions for the development
      of new interventions to improve both symptom remission and long-term RTW in sick
      listed patients with MDD.

PMID- 22967783
TI  - Modafinil and armodafinil in schizophrenia.

PMID- 22967782
TI  - Risk-taking propensity as a predictor of induction onto naltrexone treatment for
      opioid dependence.
AB  - OBJECTIVE: Heroin addiction is a chronic relapsing disorder that has devastating
      social, medical, and economic consequences. Naltrexone is an antagonist that
      blocks opioid effects and could be an effective medication for the treatment of
      opioid dependence. However, its clinical utility has been limited partly because
      of poor adherence and acceptability. Given the importance of compliance to
      naltrexone treatment for opioid dependence, the goal of the current study was to
      examine predictors involved in successful induction onto naltrexone treatment.
      METHOD: Parametric and nonparametric statistical tests were performed on data
      from a sample of 64 individuals entering treatment who met DSM-IV criteria for
      opioid dependence. The relationship between naltrexone induction (ie, inducted vs
      not inducted onto naltrexone) and risk-taking propensity, as indexed by riskiness
      on the Balloon Analogue Risk Task (BART), was examined. Participants were
      recruited from local detoxification programs, inpatient drug treatment, and other
      Baltimore programs that provided services to opioid-dependent adults (eg,
      Baltimore Needle Exchange Program) during the period from August 2007 to
      September 2008. RESULTS: Positive association was shown between risk-taking
      propensity and odds of naltrexone induction. Specifically, each 5-point increase
      in the total BART score was associated with a 25% decrease in odds of naltrexone
      induction (OR = 0.76; 95% CI, 0.58-0.99; P = .041). This association remained
      statistically significant, even after adjusting for potential confounds,
      including injection drug use and cocaine positive urine results (P = .05). After
      adjusting for the covariates, each 5-point increase in BART score was associated
      with 28% decrease in the odds of achieving the maintenance dose (adjusted OR =
      0.73; 95% CI, 0.54-0.99; P = .046). CONCLUSIONS: Risk-taking propensity was
      predictive of induction onto naltrexone treatment, above and beyond injection
      drug use and cocaine-positive urine samples.

PMID- 22967784
TI  - Shift work disorder case studies: applying management principles in clinical
      practice.
AB  - Shift work disorder (SWD) is a circadian rhythm sleep disorder characterized by
      insomnia and excessive sleepiness. SWD, which is estimated to affect 10% of
      people who work night or rotating shifts, can have serious consequences such as
      accidents, loss of productivity, and depression. By enlisting the support of
      family, identifying and treating comorbid sleep disorders, and appropriately
      timing light and dark exposure (supplemented by melatonin), clinicians can help
      many shift workers improve their ability to sleep, maintain wakefulness, and
      possibly decrease other adverse effects of shift work. More aggressive treatment
      strategies and referral to a sleep specialist should be considered for patients
      who do not respond to these simple measures.

PMID- 22967785
TI  - The appropriate use of opiates in chronic pain.
AB  - Chronic pain is a common but undertreated health problem in the United States.
      Opioids are effective for moderate-to-severe chronic pain, but these drugs must
      be used with care due to the risks for overdose and addiction. When initiating
      opioid treatment, physicians should perform a complete patient history, physical
      exam, and other appropriate testing and also assess the patient's risk for
      substance misuse, abuse, or addiction. Patients should be monitored regularly for
      both improvement of function and for aberrant drug behaviors. With proper
      monitoring and risk management, patients with chronic pain can be treated
      effectively and safely with opioids.

PMID- 22967788
TI  - Engineering of recombinant human Fcgamma receptor I by directed evolution.
AB  - Human FcgammaRI is a high-affinity receptor for human IgG. On the basis of its
      binding activity, recombinant human FcgammaRI (rhFcgammaRI) has several possible
      applications, including as a therapeutic reagent to treat immune complex-mediated
      disease and as a ligand in affinity chromatography for purification of human IgG.
      As the stability and production rate of rhFcgammaRI are low, it would need to be
      engineered for use in such applications. In this study, we demonstrated
      engineering of rhFcgammaRI by directed evolution through random mutagenesis and
      integration of mutations. Engineered rhFcgammaRI was expressed by Escherichia
      coli. Screening identified 19 amino acid mutations contributing to the thermal
      stability and production rate of rhFcgammaRI. By integration of these mutations,
      engineered rhFcgammaRI containing all 19 amino acid mutations (enFcRd) was
      constructed and showed markedly enhanced thermal stability (transition midpoint
      temperature [Tm] = 65.6 degrees C) and production rate (3.27 mg L-medium(-1)
      OD(600)(-1)) compared with wild-type rhFcgammaRI (Tm = 48.5 degrees C; production
      rate, 0.07 mg L-medium(-1) OD(600)(-1)) without a change in the specificities of
      binding to human IgG subclasses. Moreover, the binding affinity of enFcRd for
      human IgG1/k (equilibrium dissociation constant [K(D)] = 0.80 * 10(-10) M) was
      higher than that of wild-type rhFcgammaRI (K(D) = 1.23 * 10(-10) M). Our study
      showed that substantial engineering of rhFcgammaRI is possible.

PMID- 22967787
TI  - Comparison of outcomes after use of biphasic or monophasic defibrillators among
      out-of-hospital cardiac arrest patients: a nationwide population-based
      observational study.
AB  - BACKGROUND: The use and popularity of the biphasic waveform defibrillator as a
      replacement for the monophasic waveform defibrillator are increasing, but it is
      unclear whether this can improve the rate of survival among out-of-hospital
      cardiac arrest patients. This study aimed to verify the hypothesis that the
      outcome of out-of-hospital cardiac arrest patients who received defibrillation
      shock with the biphasic waveform defibrillator was better than that of patients
      who received defibrillation shock with the monophasic defibrillator. METHODS AND
      RESULTS: This prospective, nationwide, population-based, observational study
      included 21 172 out-of-hospital cardiac arrest patients with initial ventricular
      fibrillation or pulseless ventricular tachycardia from January 1, 2005, through
      December 31, 2007. Defibrillation shock was performed by monophasic defibrillator
      on 8224 (39%) patients and by biphasic defibrillator on 12 948 (61%) patients.
      The rate of survival at 1 month with minimal neurological impairment was 11.6%
      (951/8192) in the monophasic defibrillator group and 12.8% (1653/12 928) in the
      biphasic defibrillator group. Hierarchical logistic regression analysis using a
      generalized estimation equation showed no significant difference between the
      biphasic and monophasic groups in 1-month survival with minimal neurological
      impairment (adjusted odds ratio, 1.07; 95% confidence interval, 0.91-1.26;
      P=0.42). Confirmatory propensity score analyses showed similar results.
      CONCLUSIONS: Although monophasic defibrillators are being replaced by biphasic
      defibrillators, our nationwide population-based observational study failed to
      demonstrate a statistically significant association between defibrillation
      waveform and 1-month survival rate with minimal neurological impairment.

PMID- 22967789
TI  - Growth hormone treatment in boys with Duchenne muscular dystrophy and
      glucocorticoid-induced growth failure.
AB  - This study evaluated efficacy and safety of growth hormone treatment in Duchenne
      muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed
      39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth
      hormone for 1 year during a four-year period. Boys were on long-term daily
      deflazacort or prednisone (mean duration 5 +/- 2.2 years; dosing regimen
      prednisone 0.75 mg/kg/day equivalent). Primary outcomes were growth velocity and
      height-for-age z-scores (height SD) at 1 year. Height velocity increased from 1.3
      +/- 0.2 to 5.2 +/- 0.4 cm/year on growth hormone (p<0.0001). Pre-growth hormone
      decline in height SD (-0.5 +/- 0.2SD/year) stabilized at height SD -2.9 +/- 0.2
      on growth hormone (p<0.0001). The rate of weight gain was unchanged, at 2.8 +/-
      0.6 kg/year pre-growth hormone and 2.6 +/- 0.7 kg/year at 1 year. Motor function
      decline was similar pre-growth hormone and at 1 year. Cardiopulmonary function
      was unchanged. Three experienced side effects. In this first comprehensive report
      of growth hormone in Duchenne muscular dystrophy, growth hormone improved growth
      at 1 year, without detrimental effects observed on neuromuscular and
      cardiopulmonary function.

PMID- 22967790
TI  - Clinical impact of persistent hyperCKemia in a Norwegian general population: a
      case-control study.
AB  - In this case-control study we assessed the clinical impact of persistent
      hyperCKemia in a Norwegian general population. HyperCKemia was defined according
      to the NORIP- references (women 35-210 U/L, men <50 years 50-400 U/L, and men
      >=50 years 40-280 U/L). We compared the frequency of muscular symptoms and
      function, neuromuscular diseases and risk factors between 120 cases with
      persistent hyperCKemia and 130 age- and sex-matched controls with normal CK
      values, all recruited from the single-centre, population-based prospective Tromso
      Study. The participants underwent a standardized interview assessing muscle
      symptoms, physical activity, use of statins and presence of other CK risk
      factors, prior to clinical neurological and neurophysiological examination. Knee
      extensor muscle strength (Cybex NORM dynamometer) and dominant hand grip strength
      (Martin Vigorimeter) was assessed. A total of 85 cases (71%) reported either
      muscle pain, muscle stiffness or cramps, compared to 70 controls (54%) (p=0.017)
      There were no differences in muscle strength between the groups. In men, weight,
      Body Mass Index and muscle symptoms were significantly higher in the group with
      persistent hyperCKemia. In women, no differences between the groups were
      detected. Use of statins was similar in cases and controls. We diagnosed 3 women
      with previously unknown myopathy, all in the group with persistent hyperCKemia.
      This study support that CK may be used as a marker of muscular symptoms in the
      general population.

PMID- 22967791
TI  - In vitro salicylate does not further impair aging-induced brain mitochondrial
      dysfunction.
AB  - Aging and drug-induced side effects may contribute to the deterioration of
      mitochondrial bioenergetics in the brain. One hypothesis is that the combination
      of both deleterious stimuli accelerates the process of mitochondrial degradation,
      leading to progressive bioenergetic disruption. The hypothesis was tested by
      analyzing the isolated and combined effect of aging and salicylate, a vastly used
      anti-inflammatory drug, on isolated brain fractions in rats. Male Wistar rats
      were divided according to age in two groups: adult (n=8, 19 weeks of age) and
      aged (n=8, 106 weeks of age). In vitro endpoints of brain mitochondrial function
      including oxygen consumption and transmembrane electric potential (DeltaPsi) were
      evaluated in the absence and in the presence of salicylate (0.5mM). Brain
      mitochondrial susceptibility to calcium-induced permeability transition pore
      (MPTP) was also assessed. Mitochondrial oxidative stress was determined by
      measuring aconitase and manganese-superoxide dismutase (SOD) activity, and
      content in sulfhydryl groups (SH) and malondialdehyde (MDA). Mitochondrial
      content in apoptotic-related proteins Bax, Bcl-2 and cyclophilin D was determined
      by Western Blotting. Under basal, untreated, conditions, aging affected brain
      mitochondrial state 3 respiration, maximal DeltaPsi developed, ADP
      phosphorylation lag phase and calcium-induced MPTP. Interestingly, MDA decreased
      and Mn-SOD activity increased in the aged group. Brain mitochondrial Bcl-2
      content decreased and Bax/Bcl-2 ratio increased in aged group. Salicylate
      incubation for 20min increased lipid peroxidation in the aged group only and
      stimulated respiration during state 2, accompanied by decreased DeltaPsi,
      although both effects were independent of the animal age. We confirmed that both
      aging and salicylate per se impaired brain mitochondrial bioenergetics, although
      the combination of both does not seem to worsen the mitochondrial end-points
      studied.

PMID- 22967792
TI  - In vivo neurochemical characterization of clothianidin induced striatal dopamine
      release.
AB  - Clothianidin (CLO) is a neonicotinoid insecticide with selective action on
      nicotinic acetylcholine receptors. The aim of this study was to determine the
      neurochemical basis for CLO-induced striatal dopamine release using the
      microdialysis technique in freely moving and conscious rats. Intrastriatal
      administration of CLO (3.5mM), produced an increase in both spontaneous (2462 +/-
      627% with respect to basal values) and KCl-evoked (4672 +/- 706% with respect to
      basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium,
      and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin
      (TTX). To investigate the involvement of dopamine transporter (DAT), the effect
      of CLO was observed in presence of nomifensine. The coadministration of CLO and
      nomifensine produced an additive effect on striatal dopamine release. The results
      suggest that the effect of CLO on striatal dopamine release is predominantly
      mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not
      by a mechanism mediated by dopamine transporter.

PMID- 22967793
TI  - Screening of probiotic lactobacilli for inhibition of Shigella sonnei and the
      macromolecules involved in inhibition.
AB  - A total of 91 lactobacilli were screened for antimicrobial activity against
      Shigella sonnei. Agar-well assay showed that 16 lactobacilli displayed strong
      antibacterial activity against S. sonnei. The nature of these antimicrobial
      agents were investigated and shown to be dependent on their production of organic
      acids. Adhesion tests showed that 6 lactobacilli demonstrated good adherence to
      HT-29 cells, of these Lactobacillus johnsonii F0421 were selected for acid and
      bile salt tolerance properties. We further research on L. johnsonii F0421
      inhibition of S. sonnei adhesion to HT-29 cells. The result showed that L.
      johnsonii F0421 exhibited significant inhibitory activity and excluded, competed
      and displaced adhered S. sonnei by 48%, 38% and 33%, respectively. In order to
      elucidate the inhibitory functions of macromolecules involved in L. johnsonii
      F0421, the cells were treated with 5 M LiCl, 0.05 M sodium metaperiodate and
      heating and assayed for inhibition activity. The results suggested a role of S
      layer proteins on L. johnsonii F0421 cells in inhibition of the adhesion process,
      but carbohydrates do not seem to be involved. SDS-PAGE analysis confirmed the
      presence of S-layer proteins with dominant bands of approximately 40 kDa. In
      addition, 100 MUg/well of S-layer proteins from L. johnsonii F0421 cells were
      effective in inhibiting adhesion of S. sonnei to HT-29 cells. These findings
      suggest that L. johnsonii F0421 possesses the capacity for inhibition of S.
      sonnei activity as well as probiotic properties, which could serve as a potential
      novel and effective probiotic strain for use in the food industry.

PMID- 22967794
TI  - The release of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from human
      erythrocyte membranes lysed by hemolysin of Prevotella oris.
AB  - We found that a 38-kDa protein was released from erythrocyte membranes lysed by
      hemolysin of Prevotella oris, although hypotonic hemolysis did not show such a
      phenomenon. The 38-kDa protein was identified as glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) by N-terminal amino acid sequencing. This study discusses
      the relationship between GAPDH and hemolysis.

PMID- 22967795
TI  - Improved variation calling via an iterative backbone remapping and local assembly
      method for bacterial genomes.
AB  - Sequencing data analysis remains limiting and problematic, especially for low
      complexity repeat sequences and transposon elements due to inherent sequencing
      errors and short sequence read lengths. We have developed a program, ReviSeq,
      which uses a hybrid method composed of iterative remapping and local assembly
      upon a bacterial sequence backbone. Application of this method to six Brucella
      suis field isolates compared to the newly revised B. suis 1330 reference genome
      identified on average 13, 15, 19 and 9 more variants per sample than
      STAMPY/SAMtools, BWA/SAMtools, iCORN and BWA/PINDEL pipelines, and excluded on
      average 4, 2, 3 and 19 variants per sample, respectively. In total, using this
      iterative approach, we identified on average 87 variants including SNVs, short
      INDELs and long INDELs per strain when compared to the reference. Our program
      outperforms other methods especially for long INDEL calling. The program is
      available at http://reviseq.sourceforge.net.

PMID- 22967796
TI  - Enhanced cellular uptake and in vitro antitumor activity of short-chain fatty
      acid acylated daunorubicin-GnRH-III bioconjugates.
AB  - Here we report on the synthesis and biochemical characterization (enzymatic
      stability, cellular uptake, in vitro antitumor activity, membrane interaction and
      GnRH-receptor binding affinity) of novel short-chain fatty acid (SCFA) acylated
      daunorubicin-GnRH-III bioconjugates, which may serve as drug delivery systems for
      targeted cancer chemotherapy. Ser in position 4 of GnRH-III was replaced by Lys,
      followed by the acylation of its epsilon-amino group with various fatty acids.
      SCFAs are potentially chemoprotective agents by suppressing the growth of cancer
      cells and therefore may enhance the antitumor activity of the bioconjugates. We
      found that all synthesized bioconjugates had high cytostatic effect in vitro,
      were stable in cell culture medium for 6 h and degraded in the presence of rat
      liver lysosomal homogenate leading to the formation of an oxime bond-linked
      daunorubicin-Lys as the smallest active metabolite. In the presence of alpha
      chymotrypsin, all compounds were digested, the degradation rate strongly
      depending on the type of fatty acid. The bioconjugate containing Lys(nBu) in
      position 4 was taken up most efficiently by the cancer cells and exerted higher
      in vitro cytostatic effect than the previously developed GnRH-III((4)Lys(Ac),
      (8)Lys(Dau = Aoa)) or the parent GnRH-III(Dau = Aoa) bioconjugate. Our results
      could be explained by the increased binding affinity of the newly developed
      compound containing Lys(nBu) to the GnRH receptors.

PMID- 22967797
TI  - The evolution of catalytic residues and enzyme mechanism within the bacterial
      nucleoside phosphorylase superfamily 1.
AB  - Nucleoside phosphorylases are essential for the salvage and catabolism of
      nucleotides in bacteria and other organisms, and members of this enzyme
      superfamily have been of interest for the development of antimicrobial and cancer
      therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of
      different enzymes which share a general superfold and catalytic mechanism, while
      they differ in the nature of the nucleophiles used and in the nature of
      characteristic active site residues. Recently, one subfamily, the uridine
      phosphorylases, has been subdivided into two types which differ with respect to
      the mechanism of transition state stabilization, as dictated by differences in
      critical amino acid residues. Little is known about the phylogenetic distribution
      and relationship of the two different types, as well as the relationship to other
      NP-1 superfamily members. Here comparative genomic analysis illustrates that UP
      1s and UP-2s fall into monophyletic groups and are biased with respect to species
      representation. UP-1 evolved in Gram negative bacteria, while Gram positive
      species tend to predominantly contain UP-2. PNP (a sister clade to all UPs)
      contains both Gram positive and Gram negative species. The findings imply that
      the nucleoside phosphorylase superfamily 1 evolved through a series of three
      important duplications, leading to the separate, monophyletic enzyme families,
      coupled to individual lateral transfer events. Extensive horizontal transfer
      explains the occurrence of unexpected uridine phosphorylases in some genomes.
      This study provides a basis for understanding the evolution of uridine and purine
      nucleoside phosphorylases with respect to DNA/RNA metabolism and with potential
      utility in the design of antimicrobial and anti-tumor drugs.

PMID- 22967798
TI  - Effects of larval rearing temperature on immature development and West Nile virus
      vector competence of Culex tarsalis.
AB  - BACKGROUND: Temperature is known to induce changes in mosquito physiology,
      development, ecology, and in some species, vector competence for arboviruses.
      Since colonized mosquitoes are reared under laboratory conditions that can be
      significantly different from their field counterparts, laboratory vector
      competence experiments may not accurately reflect natural vector-virus
      interactions. METHODS: We evaluated the effects of larval rearing temperature on
      immature development parameters and vector competence of two Culex tarsalis
      strains for West Nile virus (WNV). RESULTS: Rearing temperature had a significant
      effect on mosquito developmental parameters, including shorter time to pupation
      and emergence and smaller female body size as temperature increased. However,
      infection, dissemination, and transmission rates for WNV at 5, 7, and 14 days
      post infectious feeding were not consistently affected. CONCLUSIONS: These
      results suggest that varying constant larval rearing temperature does not
      significantly affect laboratory estimates of vector competence for WNV in Culex
      tarsalis mosquitoes.

PMID- 22967799
TI  - Human epididymis protein 4 (HE4) and ovarian cancer prognosis.
AB  - OBJECTIVE: A cohort study was conducted to evaluate whether preoperative plasma
      HE4 levels could predict the occurrence of death (primary endpoint) and
      progression (secondary endpoint) in women with ovarian cancer (OC). METHODS:
      Between 1998 and 2006, we recruited 136 women newly diagnosed with OC of any FIGO
      stage at the University Hospital, CHUQ-L'Hotel-Dieu de Quebec, Canada. HE4 was
      measured using the Abbott's ARCHITECT HE4 assay. Dates of death were obtained by
      record linkage with the Quebec mortality files. Progression was evaluated using
      the CA-125 or the RECIST criteria, as recommended by the Gynecology Cancer
      Intergroup. Adjusted hazard ratios (HR) of death and progression, as well as
      their 95% confidence intervals (CI), were estimated using the Cox proportional
      hazard regression model. RESULTS: Preoperative levels of HE4 were strongly
      associated with all OC standard prognostic factors. HE4 levels increased
      significantly with age (p=0.02), FIGO stage (p<0.0001), grade (p=0.005),
      preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels
      above the median value (394 pmol/L) were significantly associated with mortality
      (HR=2.17; 95% CI: 1.42-3.32) and progression (HR=1.81; 95% CI: 1.21-2.72). After
      adjustment for the FIGO stage, which was the only factor significantly associated
      with prognosis in multivariate analyses, the association of HE4 with death
      remained statistically significant (HR=1.67; 95% CI: 1.08-2.59). However, the
      association with progression was no longer significant (HR=1.32; 95% CI: 0.87
      1.99). CONCLUSION: These results show that preoperative the plasma level of HE4
      is a marker of OC aggressiveness and a predictor of death.

PMID- 22967800
TI  - mTOR inhibitors in breast cancer: a systematic review.
AB  - PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt
      pathway is heavily deregulated in breast cancer, the application of mTOR
      inhibitors in breast cancer patients seems warranted. This is the first
      systematic review according to PRISMA guidelines to synthesize all available data
      of mTOR inhibitors in all subcategories of breast cancer. The search strategy
      retrieved 16 studies evaluating everolimus (1492 patients), seven studies
      examining temsirolimus (1245 patients), one study evaluating sirolimus (400
      patients) and two studies evaluating MKC-1 (60 patients). The Breast Cancer
      Trials of Oral Everolimus-2 (BOLERO-2) study has marked a turning point in the
      evaluation of everolimus in the treatment of estrogen receptor positive breast
      cancer. Given the positive results, everolimus has entered NCCN 2012 guidelines,
      and its approval of its combination with exemestane by FDA and EMA is imminent.
      In addition, the promising antitumor activity and long-term disease control
      further suggest that mTOR inhibition with everolimus may provide an avenue for
      achieving long-lasting benefit from trastuzumab-based therapy in HER2-positive
      patients. Regarding temsirolimus, it seems that the agent may play, in the
      future, a role in the treatment of metastatic breast cancer; importantly,
      however, there is an unmet need to find its optimal target subpopulation.

PMID- 22967801
TI  - Intestinal helminth fauna of the South American sea lion Otaria flavescens and
      fur seal Arctocephalus australis from northern Patagonia, Argentina.
AB  - We report on the intestinal helminth fauna of 56 South American sea lions, Otaria
      flavescens, and 5 South American fur seals, Arctocephalus australis, from
      northern Patagonia, Argentina. A total of 97,325 helminth specimens were
      collected from sea lions. Gravid individuals were represented by 6 species of
      parasites: 1 digenean (Ascocotyle (Ascocotyle) patagoniensis), 1 cestode
      (Diphyllobothrium spp.), 3 nematodes (Uncinaria hamiltoni, Contracaecum ogmorhini
      s.s., Pseudoterranova cattani) and 1 acanthocephalan (Corynosoma australe). In
      addition, third-stage larvae of 2 nematodes (Contracaecum sp. and Anisakis sp.
      type I) and 3 juvenile acanthocephalans (Andracantha sp., Profilicollis
      chasmagnathi and Corynosoma cetaceum) were also collected. Andracantha sp., C.
      ogmorhini s.s. and P. chasmagnathi represent new host records. A total of 1516
      helminth specimens were collected from fur seals. Gravid individuals were
      represented by three species of parasites, namely, Diphyllobothrium spp., C.
      ogmorhini s.s. and C. australe. In addition, larvae of Contracaecum sp. and P.
      cattani, juveniles of C. cetaceum and immature cestodes (Tetrabothriidae gen.
      sp.) were also collected. Corynosoma australe was the most prevalent and abundant
      parasite in both hosts, accounting for >90% of all specimens. Sea lions and furs
      seals from northern Patagonia harbour the intestinal helminth communities that
      could be predicted for otariids, i.e. the combination of species of the genera
      Corynosoma, Diphyllobothrium, Pseudoterranova, Contracaecum and, in pups,
      Uncinaria. Additionally, both species of otariid are apparently unsuitable hosts
      (i.e. non-hosts) for as many as five parasite taxa. The inclusion or exclusion of
      these species affects estimation of species richness at both component community
      (11 versus 6 species in sea lions; 7 versus 3 species in fur seals) and
      infracommunity (mean: 3.1 versus 2.6 in sea lions; 2.2 versus 1.7 species)
      levels. Information about the reproductive status of helminth species is often
      lacking in parasitological surveys on otariids and other marine vertebrates, but
      it is of significance to improve precision in parascript studies or ecological
      meta-analyses. 

PMID- 22967803
TI  - Rethink the war on cancer - directional metastasis driven by survival advantage
      gradient.

PMID- 22967802
TI  - Preclinical evaluation of sunitinib, a multi-tyrosine kinase inhibitor, as a
      radiosensitizer for human prostate cancer.
AB  - BACKGROUND: Many prostate cancers demonstrate an increased expression of growth
      factor receptors such as vascular endothelial growth factor receptor (VEGFR) and
      platelet derived growth factor receptor (PDGFR) which have been correlated with
      increased resistance to radiotherapy and poor prognosis in other tumors.
      Therefore, response to radiation could potentially be improved by using
      inhibitors of these abnormally activated pathways. We have investigated the
      radiosensitizing effects of sunitinib, a potent, multi-tyrosine kinase inhibitor
      of the VEGFR and PDGFR receptors, on human prostate cancer cells. METHODS: The
      radiosensitizing effects of sunitinib were assessed on human prostate cancer cell
      lines DU145, PC3 and LNCaP by clonogenic assay. Sunitinib's ability to inhibit
      the activities of its key targets was determined by immunoblot analysis. The
      radiosensitizing effects of sunitinib in vivo were tested on human tumor
      xenografts growing in nude mice where response was assessed by tumor growth
      delay. RESULTS: Clonogenic survival curve assays for both DU145 and PC3 cells
      showed that the surviving fraction at 2 Gy was reduced from 0.70 and 0.52 in
      controls to 0.44 and 0.38, respectively, by a 24 hr pretreatment with 100 nM
      sunitinib. LNCaP cells were not radiosensitized by sunitinib. Dose dependent
      decreases in VEGFR and PDGFR activation were also observed following sunitinib in
      both DU145 and PC3 cells. We assessed the ability of sunitinib to radiosensitize
      PC3 xenograft tumors growing in the hind limb of nude mice. Sunitinib given
      concurrently with radiation did not prolong tumor growth delay. However, when
      animals were treated with sunitinib commencing the day after fractionated
      radiation was complete, tumor growth delay was enhanced compared to radiation
      alone. CONCLUSIONS: We conclude, based on the in vivo results, that sunitinib and
      radiation do not interact directly to radiosensitize the PC3 tumor cells in vivo
      as they did in vitro. The fact that tumor growth delay was enhanced when
      sunitinib was given after radiotherapy was completed suggests that sunitinib may
      be acting on the irradiated tumor stroma and suppressing its ability to sustain
      regrowth of the irradiated tumor. Based on these preclinical findings, we suggest
      that the combination of sunitinib and radiation for the treatment of prostate
      cancer deserves further development.

PMID- 22967804
TI  - Combined therapeutic application of mTOR inhibitor and vitamin D(3) for
      inflammatory bone destruction of rheumatoid arthritis.
AB  - Inflammatory bone destruction is a prominent feature and a cause of substantial
      morbidity in several inflammatory diseases, including rheumatoid arthritis (RA),
      periodontitis, and peri-prosthetic loosening. Osteoclasts are unique,
      multinucleated giant cells that effectively resorb bone and thus are directly
      responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR
      pathway has been well known to play important roles in regulating adaptive and
      innate immune cell function. In addition to play roles in immune responses,
      several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for
      osteoclast differentiation and survival. These results suggest that inhibition of
      PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory
      diseases, including RA. However, the clinical use of mTOR inhibitors may be
      hampered due to limited clinical efficacy and frequent toxic side effects. In the
      treatment of RA, combination therapy with various disease-modifying antirheumatic
      drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit
      the side effects. In this report, we show several experimental evidences that
      vitamin D(3) modulates mTOR pathway, and present a hypothesis that the
      combination of mTOR inhibitor and vitamin D(3) can effectively inhibit osteoclast
      differentiation and function in chronic inflammatory condition such as RA,
      therefore this combination will be a powerful therapeutic regimen in preventing
      the inflammation-induced bone destruction in RA.

PMID- 22967805
TI  - RADAR reference adult, pediatric, and pregnant female phantom series for internal
      and external dosimetry.
AB  - A new generation of reference computational phantoms, based on image-based models
      tied to the reference masses defined by the International Commission on
      Radiological Protection (ICRP) for dose calculations, is presented. METHODS:
      Anatomic models based on nonuniform rational b-spline modeling techniques were
      used to define reference male and female adults, 15-y-olds, 10-y-olds, 5-y-olds,
      1-y-olds, newborns, and pregnant women at 3 stages of gestation, using the
      defined reference organ masses in ICRP publication 89. Absorbed fractions and
      specific absorbed fractions for internal emitters were derived using standard
      Monte Carlo radiation transport simulation codes. RESULTS: Differences were
      notable between many pairs of organs in specific absorbed fractions because of
      the improved realism of the models, with adjacent organs usually closer and
      sometimes touching. Final estimates of absorbed dose for radiopharmaceuticals,
      for example, were only slightly different overall, as many of the differences
      were small and most pronounced at low radiation energies. Some new important
      organs were defined (salivary glands, prostate, eyes, and esophagus), and the
      identity of a few gastrointestinal tract organs changed. CONCLUSION: A new
      generation of reference models for standardized internal and external dose
      calculations has been defined. The models will be implemented in standardized
      software for internal dose calculations and be used to produce new standardized
      dose estimates for radiopharmaceuticals and other applications.

PMID- 22967806
TI  - Whole-body distribution and radiation dosimetry of 11C-(+)-PHNO, a D2/3 agonist
      ligand.
AB  - Using PET, we measured the whole-body distribution of (11)C-(+)-PHNO ((11)C-(+)-4
      propyl-9-hydroxynaphthoxazine), a D(2/3) agonist, as a function of time in adult
      subjects in order to determine the internal radiation dose. METHODS: PET whole
      body data were acquired after the injection of (11)C-(+)-PHNO (~360 MBq) in 6
      healthy subjects (3 male and 3 female). The PET acquisition duration was a
      maximum of 112.5 min, and 9 discrete time frames were obtained. After
      reconstruction of the emission data, 6 organs were identified in the images as
      exhibiting uptake above background levels. Regions of interest were delineated on
      these organs, and time-activity curves were generated. The time-activity curve
      data were corrected for the injected activity, specific organ density, and
      volume, from which normalized accumulated activities (previously known as
      residence times) were calculated. The normalized accumulated activities were then
      used with the software code OLINDA/EXM 1.1 to calculate the internal doses for
      the standard adult male and female models. RESULTS: The mean effective dose was
      estimated to be 4.5 +/- 0.3 MUSv/MBq when all subjects were included and the male
      model was applied for the dosimetry calculation, and the mean effective dose was
      estimated to be 5.2 +/- 0.2 MUSv/MBq when the females were considered separately
      and the female model was applied for the calculation. The organ receiving the
      highest dose was the liver (17.9 +/- 3.9 MUSv/MBq), followed by the kidneys (14.3
      +/- 3.6 MUSv/MBq) and the urinary bladder wall (13.5 +/- 3.7 MUSv/MBq).
      CONCLUSION: The estimated radiation doses for (11)C-(+)-PHNO are similar to those
      reported for other radiotracers labeled with (11)C. (11)C-(+)-PHNO may be used
      for multiple PET scans in the same subject and remain within regulatory
      guidelines.

PMID- 22967808
TI  - Type III membranoproliferative glomerulonephritis in a patient with primary
      Sjogren's syndrome.
AB  - Renal involvement in the form of glomerulonephritis in Sjogren's syndrome (SS) is
      less common and usually a latent sequel in the course of the disease. We report a
      patient with Type III membarnoproliferative glomerulonephritis (MPGN) with
      hypothyroidism, which precedes the onset of the clinical manifestation of SS. She
      received immunosuppressions consisting of i.v. cyclophosphamide and high-dose
      corticosteroid and subsequently oral corticosteroid resulting in complete
      remission of nephrotic syndrome. To our knowledge, this is the first report of
      successfully treated Type III MPGN associated with SS.

PMID- 22967807
TI  - Genome editing of human embryonic stem cells and induced pluripotent stem cells
      with zinc finger nucleases for cellular imaging.
AB  - RATIONALE: Molecular imaging has proven to be a vital tool in the
      characterization of stem cell behavior in vivo. However, the integration of
      reporter genes has typically relied on random integration, a method that is
      associated with unwanted insertional mutagenesis and positional effects on
      transgene expression. OBJECTIVE: To address this barrier, we used genome editing
      with zinc finger nuclease (ZFN) technology to integrate reporter genes into a
      safe harbor gene locus (PPP1R12C, also known as AAVS1) in the genome of human
      embryonic stem cells and human induced pluripotent stem cells for molecular
      imaging. METHODS AND RESULTS: We used ZFN technology to integrate a construct
      containing monomeric red fluorescent protein, firefly luciferase, and herpes
      simplex virus thymidine kinase reporter genes driven by a constitutive ubiquitin
      promoter into a safe harbor locus for fluorescence imaging, bioluminescence
      imaging, and positron emission tomography imaging, respectively. High efficiency
      of ZFN-mediated targeted integration was achieved in both human embryonic stem
      cells and induced pluripotent stem cells. ZFN-edited cells maintained both
      pluripotency and long-term reporter gene expression. Functionally, we
      successfully tracked the survival of ZFN-edited human embryonic stem cells and
      their differentiated cardiomyocytes and endothelial cells in murine models,
      demonstrating the use of ZFN-edited cells for preclinical studies in regenerative
      medicine. CONCLUSION: Our study demonstrates a novel application of ZFN
      technology to the targeted genetic engineering of human pluripotent stem cells
      and their progeny for molecular imaging in vitro and in vivo.

PMID- 22967809
TI  - Honouring patient's resuscitation wishes: a multiphased effort to improve
      identification and documentation.
AB  - BACKGROUND: Do Not Resuscitate (DNR) orders are intended to safeguard patients'
      autonomy and prevent unwanted resuscitative care. However, DNR orders may be
      miscommunicated between health care providers, leading to errors honoring patient
      wishes during cardiac arrest events. This project focused on improving accuracy
      of DNR ordering processes for an academic, tertiary care hospital. INTERVENTION:
      We describe a performance improvement process and outcomes for implementation of
      an inpatient electronic ordering system that included an automated, decentralized
      printing process for resuscitation status armbands. Specific phases of this
      project involved: (a) identification of common factors contributing to errors
      honoring patients' resuscitation wishes, (b) design of an electronic ordering
      process, (c) design and integration of a new DNR armband and (d) evaluation of
      the impact of changes on communication accuracy. The primary outcome was
      percentage of patients with incorrect designation of resuscitation status on
      armbands compared to the active resuscitation order in the electronic medical
      record. RESULTS: After implementation of an electronic ordering process we
      identified that 37/196 (19%) patients had an armband that did not reflect their
      documented wishes versus 2/103 (2%) after integration of automated armband
      printing into the process (p<0.001). No armband discrepancies were found after
      the first two weeks of post-implementation audits. CONCLUSIONS: Design and
      implementation of an electronic ordering and armband labeling process reduced
      discrepancies between patient wishes and the armband labeling of the patient's
      desired DNR status. It is anticipated that these improvements will reduce the
      risk of adverse outcomes, and better align clinical processes with patient
      wishes.

PMID- 22967810
TI  - Synthesis of quinolinomorphinan derivatives as highly selective delta opioid
      receptor ligands.
AB  - We have reported previously the novel delta opioid agonist KNT-127 which showed
      high affinity and selectivity for the delta receptor. Moreover, the analgesic
      effect of subcutaneously administered KNT-127 was more potent than that of a
      prototypical delta agonist (-)-TAN-67 in the acetic acid writhing test. This
      study of the structure-activity relationship of KNT-127 derivatives focused on
      the introduction of substituents onto the 5'-, 6'-, 7'- or 8'-position of the
      quinoline ring and revealed that many derivatives with 5'- or 8'-substituents
      showed high affinities and selectivities for the delta receptor. Especially, SYK
      153 with an 8'-OH group showed the highest affinity and the most balanced and
      highest selectivity for the delta receptor among the synthesized compounds.

PMID- 22967811
TI  - Design, synthesis and evaluation of novel metalloproteinase inhibitors based on L
      tyrosine scaffold.
AB  - A series of novel L-tyrosine derivatives were designed, synthesized and assayed
      for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and histone
      deacetylase 8 (HDAC-8). The results showed that these L-tyrosine derivatives
      exhibited inhibitory profiles against MMP-2 and HDAC-8. The compounds 6h
      (IC(50)=0.013 +/- 0.001 MUM) and 6j (IC(50)=0.017 +/- 0.001 MUM) were equal
      potent MMP-2 inhibitors to the positive control NNGH (IC(50)=0.014 +/- 0.001
      MUM). As for HDAC-8 inhibition, some of the hydroxamate compounds, such as 6d
      (IC(50)=3.6 +/- 0.2 MUM) and 6c (IC(50)=5.8 +/- 0.5 MUM), were equal potent to
      the positive control SAHA (IC(50)=1.6 +/- 0.1 MUM). Structure-activity
      relationships were also briefly discussed.

PMID- 22967812
TI  - The association of retinol-binding protein 4 with metabolic syndrome and obesity
      in adolescents: the effects of gender and sex hormones.
AB  - OBJECTIVES: Retinol-binding protein 4 (RBP4) has a role in the development of
      insulin resistance (IR), type 2 diabetes, obesity, and metabolic syndrome among
      adults. However, data among adolescents are limited, and the effects of gender
      and sex hormones on RBP4 are not well defined. MATERIALS/METHODS: A total of 1082
      adolescents were enrolled and categorized based on their body mass index. Blood
      samples were collected, and biochemical characteristics, sex hormones, RBP4
      concentrations, and IR were determined. RESULTS: Testosterone and estradiol were
      not directly correlated with RBP4 concentrations in both genders. Multivariate
      regression analysis revealed that fasting plasma glucose (FPG), triglyceride
      (TG), and testosterone levels were independently associated with RBP4
      concentrations in boys; also, there was a trend of increasing RBP4 levels with
      the severity of obesity. CONCLUSION: Plasma RBP4 concentrations correlated with
      obesity and cardiovascular risk factors, predominantly evident in boys.
      Testosterone, FPG, and TG levels were independent predictors of RBP4
      concentrations.

PMID- 22967813
TI  - Home safety practices in an urban low-income population: level of agreement
      between parental self-report and observed behaviors.
AB  - Home-related injuries are overrepresented in children from low-income households.
      The objectives of this study were to determine frequencies of home safety
      behaviors and the level of agreement between parental self-report and observed
      safety practices in low-income homes. In a prospective, interventional home
      injury prevention study of 49 low-income families with children <5 years old, a
      trained home visitor administered baseline parental home safety behavior
      questionnaires and assessments. There was high agreement between caregiver self
      report and home visitor observation for lack of cabinet latch (99%, 95%
      confidence interval [CI] = 88%-99%) and stair gate use (100%, 95% CI = 88-100%).
      There was lower agreement for the safe storage of cleaning supplies (62%, 95% CI
      = 46%-75%), sharps (74%, 95% CI = 59%-85%), and medicines/vitamins (83%, 95% CI =
      69%-92%) because of the overreporting of safe practices. Self-reports of some
      home safety behaviors are relatively accurate, but certain practices may need to
      be verified by direct assessment.

PMID- 22967814
TI  - Chymotrypsin-like serine proteinases are involved in the maintenance of cell
      viability.
AB  - An increasing number of studies have implicated serine proteinases in the
      development of apoptosis. In this study, we assessed the ability of a set of
      highly specific irreversible inhibitors (activity probes), incorporating an alpha
      amino alkane diphenyl phosphonate moiety, to modulate cell death. In an initial
      assessment of the cellular toxicity of these activity probes, we discovered that
      one example, N-alpha-tetramethylrhodamine phenylalanine diphenylphosphonate {TMR
      Phe(P)(OPh)(2)} caused a concentration-dependent decrease in the viability of
      HeLa and U251 mg cells. This reduced cell viability was associated with a time
      dependent increase in caspase-3 activity, PARP cleavage and phosphatidylserine
      translocation, establishing apoptosis as the mechanism of cell death. SDS-PAGE
      analysis of cell lysates prepared from the HeLa cells treated with TMR
      Phe(P)(OPh)(2), revealed the presence of a fluorescent band of molecular weight
      58 kDa. Given that we have previously reported on the use of this type of
      activity probe to reveal active proteolytic species, we believe that we have
      identified a chymotrypsin-like serine proteinase activity integral to the
      maintenance of cell viability.

PMID- 22967815
TI  - NMR-based metabolomics study of canine bladder cancer.
AB  - Bladder cancer is one of the leading lethal cancers worldwide. With the high risk
      of recurrence for bladder cancer following the initial diagnoses, lifelong
      monitoring of patients is necessary. The lack of adequate sensitivity and
      specificity of current noninvasive monitoring approaches including urine
      cytology, other urine tests, and imaging, underlines the importance of studies
      that focus on the detection of more reliable biomarkers for this cancer. The
      emerging area of metabolomics, which deals with the analysis of a large number of
      small molecules in a single step, promises immense potential for discovering
      metabolite markers for screening and monitoring treatment response and recurrence
      in patients with bladder cancer. Since naturally-occurring canine transitional
      cell carcinoma of the urinary bladder is very similar to human invasive bladder
      cancer, spontaneous canine transitional cell carcinoma has been applied as a
      relevant animal model of human invasive transitional cell carcinoma. In this
      study, we have focused on profiling the metabolites in urine from dogs with
      transitional cell carcinoma and healthy control dogs combining nuclear magnetic
      resonance spectroscopy and statistical analysis methods. (1)H NMR-based
      metabolite profiling analysis was shown to be an effective approach for
      differentiating samples from dogs with transitional cell carcinoma and healthy
      controls based on a partial least square-discriminant analysis of the NMR
      spectra. In addition, there were significant differences in the levels of six
      individual metabolites between samples from dogs with transitional cell carcinoma
      and the control group based on the Student's t-test. These metabolites were
      selected to build a separate partial least square-discriminant analysis model
      that was then used to test the classification accuracy. The result showed good
      classification between transitional cell carcinoma and control groups with the
      area under the receiver operating characteristic curve of 0.85. The sensitivity
      and specificity of the model were 86% and 78%, respectively. These results
      suggest that urine metabolic profiling may have potential for early detection of
      bladder cancer and of bladder cancer recurrence following treatment, and may
      enhance our understanding of the mechanisms involved.

PMID- 22967816
TI  - Associative and occasion-setting properties of contextual cues in flavor-nutrient
      learning in rats.
AB  - This article studied the role of contextual cues, present at the time flavor
      conditioning occurs, on intake behavior in rats. In three experiments animals
      were given flavor-sucrose pairings in one distinctive context (Context A) whereas
      the flavor was presented unreinforced in an alternative context (Context B).
      Experiments 1 and 2 used a simple Pavlovian discrimination procedure (A: X+, B: X
      ) and tested consumption of flavor X in each context. Consumption of the flavor
      was higher in Context A than in Context B. In Experiment 2 rats were given a
      treatment (exposure to water in the context) designed to extinguish associations
      between the context and the reinforcer. This procedure did not affect the ability
      of the context to control intake of flavor X. Experiment 3 used a biconditional
      discrimination procedure (A: X+, Y-; B: X-, Y+; where X and Y were different
      flavors) in which no single context or flavor predicted reinforcement. The rats
      learned this discrimination, consuming more of each flavor in the context in
      which it had previously been reinforced. The results are interpreted in terms
      both of the effects of direct associations between context and events presented
      in them, and in terms of the modulatory or occasion-setting properties of the
      context.

PMID- 22967817
TI  - Reproducibility of the measurement of sweet taste preferences.
AB  - Developing interventions to prevent and treat obesity are medical and public
      health imperatives. Taste is a major determinant of food intake and reliable
      methods to measure taste preferences need to be established. This study aimed to
      establish the short-term reproducibility of sweet taste preference measurements
      using 5-level sucrose concentrations in healthy adult volunteers. We defined
      sweet taste preference as the geometric mean of the preferred sucrose
      concentration determined from two series of two-alternative, forced-choice
      staircase procedures administered 10min apart on a single day. We repeated the
      same procedures at a second visit 3-7days later. Twenty-six adults (13 men and 13
      women, age 33.2+/-12.2years) completed the measurements. The median number of
      pairs presented for each series was three (25th and 75th percentiles: 3, 4). The
      intraclass correlation coefficients between the measurements was 0.82 (95%
      confidence interval [CI]: 0.63-0.92) within a few days. This study showed high
      short-term reproducibility of a simple, 5-level procedure for measuring sweet
      taste preferences. This method may be useful for assessing sweet taste
      preferences and the risks resulting from those preferences.

PMID- 22967818
TI  - Defining, regulating and using saccharin at the outset of the industrial food era
      (1888-1914).
AB  - This paper focuses on the in-depth debates on saccharin that took place around
      1900. In numerous discussions among chemists and physicians the sweetener was
      defined and redefined in a complex way and with a clear lack of agreement among
      experts. Nevertheless, this fact did not hinder the search for an international
      agreement on the regulation of saccharin in the food market. This paper analyses
      these discussions by building on the new trends in material culture studies, and
      estimates the real impact of medical and chemical expertise on international
      agreements.

PMID- 22967819
TI  - Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro:
      implications in understanding asthma.
AB  - Asthma is a chronic obstructive airway disease characterised by airway
      hyperresponsiveness (AHR) and airway wall remodelling. The effector of airway
      narrowing is the contraction of airway smooth muscle (ASM), yet the question of
      whether an inherent or acquired dysfunction in ASM contractile function plays a
      significant role in the disease pathophysiology remains contentious. The
      difficulty in determining the role of ASM lies in limitations with the models
      used to assess contraction. In vivo models provide a fully integrated
      physiological response but ASM contraction cannot be directly measured. Ex vivo
      and in vitro models can provide more direct assessment of ASM contraction but the
      loss of factors that may modulate ASM responsiveness and AHR, including
      interaction between multiple cell types and disruption of the mechanical
      environment, precludes a complete understanding of the disease process. In this
      review we detail key advantages of common in vivo, ex vivo and in vitro models of
      ASM contraction, as well as emerging tissue engineered models of ASM and whole
      airways. We also highlight important findings from each model with respect to the
      pathophysiology of asthma.

PMID- 22967820
TI  - Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of
      Parkinson disease--resemblance to the effect of amphetamine drugs of abuse.
AB  - Parkinson disease (PD) is a chronic and progressive neurological disease
      associated with a loss of dopaminergic neurons. In most cases the disease is
      sporadic but genetically inherited cases also exist. One of the major
      pathological features of PD is the presence of aggregates that localize in
      neuronal cytoplasm as Lewy bodies, mainly composed of alpha-synuclein (alpha-syn)
      and ubiquitin. The selective degeneration of dopaminergic neurons suggests that
      dopamine itself may contribute to the neurodegenerative process in PD.
      Furthermore, mitochondrial dysfunction and oxidative stress constitute key
      pathogenic events of this disorder. Thus, in this review we give an actual
      perspective to classical pathways involving these two mechanisms of
      neurodegeneration, including the role of dopamine in sporadic and familial PD, as
      well as in the case of abuse of amphetamine-type drugs. Mutations in genes
      related to familial PD causing autosomal dominant or recessive forms may also
      have crucial effects on mitochondrial morphology, function, and oxidative stress.
      Environmental factors, such as MPTP and rotenone, have been reported to induce
      selective degeneration of the nigrostriatal pathways leading to alpha-syn
      positive inclusions, possibly by inhibiting mitochondrial complex I of the
      respiratory chain and subsequently increasing oxidative stress. Recently,
      increased risk for PD was found in amphetamine users. Amphetamine drugs have
      effects similar to those of other environmental factors for PD, because long-term
      exposure to these drugs leads to dopamine depletion. Moreover, amphetamine
      neurotoxicity involves alpha-syn aggregation, mitochondrial dysfunction, and
      oxidative stress. Therefore, dopamine and related oxidative stress, as well as
      mitochondrial dysfunction, seem to be common links between PD and amphetamine
      neurotoxicity.

PMID- 22967821
TI  - Does invasive Chondrostoma nasus shift the parasite community structure of
      endemic Parachondrostoma toxostoma in sympatric zones?
AB  - BACKGROUND: The composition of parasite communities in two cyprinid species in
      southern France - native and threatened Parachondrostoma toxostoma and introduced
      Chondrostoma nasus - was investigated. In sympatry, these two species form two
      hybrid zones in the Durance and Ardeche Rivers. Due to their different feeding
      preference and habitat positions in allopatry, we supposed a difference in
      parasite communities between fish species. We expected more similar parasite
      communities in sympatric zones associated with habitat overlap (facilitating the
      transmission of ectoparasites) and similar feeding (more generalist behaviour
      when compared to allopatry, facilitating the transmission of endoparasites) in
      both fish species. Finally, we investigated whether P. toxostoma x C. nasus
      hybrids are less parasitized then parental species. METHODS: One allopatric
      population of each fish species plus two sympatric zones were sampled. Fish were
      identified using cytochrome b gene and 41 microsatellites loci and examined for
      all metazoan parasites. RESULTS: A high Monogenea abundance was found in both
      allopatric and sympatric populations of C. nasus. Trematoda was the dominant
      group in parasite communities of P. toxostoma from the allopatric population. In
      contrast, the populations of P. toxostoma in sympatric zones were parasitized by
      Dactylogyrus species found in C. nasus populations, but their abundance in
      endemic species was low. Consequently, the similarity based on parasite
      presence/absence between the sympatric populations of P. toxostoma and C. nasus
      was high. Sympatric populations of P. toxostoma were more similar than allopatric
      and sympatric populations of this species. No difference in ectoparasite
      infection was found between P. toxostoma and hybrids, whilst C. nasus was more
      parasitized by Monogenea. CONCLUSIONS: The differences in endoparasites between
      P. toxostoma and C. nasus in allopatry are probably linked to different feeding
      or habitat conditions, but host-parasite evolutionary associations also play an
      important role in determining the presence of Chondrostoma-specific monogeneans.
      Our findings suggest that Dactylogyrus expanded with the source host C. nasus
      into introduced areas and that P. toxostoma became infected after contact with C.
      nasus. Although the genotype of P. toxostoma and recombinant genotypes of hybrids
      are susceptible to Dactylogyrus transmitted from C. nasus, the intensity of
      infection is low in these genotypes.

PMID- 22967822
TI  - Evaluating the demand for carbon sequestration in olive grove soils as a strategy
      toward mitigating climate change.
AB  - In this paper we present an estimate of the economic value of carbon
      sequestration in olive grove soils derived from the implementation of different
      agricultural management systems. Carbon sequestration is considered jointly with
      other environmental co-benefits, such as enhanced erosion prevention and
      increased biodiversity. The estimates have been obtained using choice experiments
      and show that there is a significant demand from society for these environmental
      services. From a policy perspective, an agri-environmental scheme that delivers
      the highest level of each environmental service would be valued by society at 121
      Euros per hectare. If we focus on carbon sequestration, each ton of CO(2) would
      be valued at 17 Euros. These results show that there is scope to include
      agricultural soil carbon sequestration in climate change mitigation strategies
      and to provide guidance for setting payments for agri-environmental schemes
      promoting soil management changes.

PMID- 22967823
TI  - Evaluating the effectiveness of water restrictions: a case study from Southeast
      Florida.
AB  - One of the most commonly employed water conservation strategies is to restrict
      lawn watering to limited times on specified days. Water managers typically assume
      that limiting the frequency and duration of lawn watering will reduce water use.
      Consequently, the effectiveness of water restrictions is often evaluated based on
      observed compliance to the specified schedule, whether or not actual reductions
      in water use are achieved. This assessment approach is more practical than
      quantifying the reduction in water use brought about by restrictions because
      quantification of lawn water use is hampered by difficulties in disaggregating
      the various components of residential water use. Dual meters to separately meter
      the portion of public supply devoted to lawn water use are rare, and for
      households that withdraw water from private wells, canals, or ponds for lawn
      watering, there is no record of such water use at all. As a consequence of this
      gap in water use data, compliance to a prescribed frequency of watering is often
      equated with effectiveness. In this paper we develop an alternative metric for
      evaluating the effectiveness of water restrictions and present a case study in a
      suburban area in Southeast Florida that illustrates some of the challenges of
      quantifying lawn water use and explores some of the limitations of day of the
      week water restrictions as a conservation strategy.

PMID- 22967824
TI  - Kinematics analysis of ankle inversion ligamentous sprain injuries in sports:
      five cases from televised tennis competitions.
AB  - BACKGROUND: Ankle ligamentous sprain is common in sports. The most direct way to
      study the mechanism quantitatively is to study real injury cases; however, it is
      unethical and impractical to produce an injury in the laboratory. A recently
      developed, model-based image-matching motion analysis technique allows
      quantitative analysis of real injury incidents captured in televised events and
      gives important knowledge for the development of injury prevention protocols and
      equipment. To date, there have been only 4 reported cases, and there is a need to
      conduct more studies for a better understanding of the mechanism of ankle
      ligamentous sprain injury. PURPOSE: This study presents 5 cases in tennis and a
      comparison with 4 previous cases for a better understanding of the mechanism of
      ankle ligamentous sprain injury. STUDY DESIGN: Case series; level of evidence, 4.
      METHODS: Five sets of videos showing ankle sprain injuries in televised tennis
      competition with 2 camera views were collected. The videos were transformed,
      synchronized, and rendered to a 3-dimensional animation software. The dimensions
      of the tennis court in each case were obtained to build a virtual environment,
      and a skeleton model scaled to the injured athlete's height was used for the
      skeleton matching. Foot strike was determined visually, and the profiles of the
      ankle joint kinematics were individually presented. RESULTS: There was a pattern
      of sudden inversion and internal rotation at the ankle joint, with the peak
      values ranging from 48 degrees -126 degrees  and 35 degrees -99 degrees ,
      respectively. In the sagittal plane, the ankle joint fluctuated between plantar
      flexion and dorsiflexion within the first 0.50 seconds after foot strike. The
      peak inversion velocity ranged from 509 to 1488 deg/sec. CONCLUSION: Internal
      rotation at the ankle joint could be one of the causes of ankle inversion sprain
      injury, with a slightly inverted ankle joint orientation at landing as the
      inciting event. To prevent the foot from rolling over the edge to cause a sprain
      injury, tennis players who do lots of sideward cutting motions should try to land
      with a neutral ankle orientation and keep the center of pressure from shifting
      laterally.

PMID- 22967825
TI  - The function of the acromioclavicular and coracoclavicular ligaments in shoulder
      motion: a whole-cadaver study.
AB  - BACKGROUND: Scapulothoracic dyskinesis is an important consequence of
      acromioclavicular joint dislocations. However, no reports have described changes
      in 3-dimensional motions of the scapula and clavicle with respect to the thorax
      caused by acromioclavicular joint dislocation. HYPOTHESIS: Sectioning of the
      acromioclavicular (AC) and coracoclavicular (CC) ligaments affects scapular and
      clavicular motion in a whole-cadaver model. STUDY DESIGN: Controlled laboratory
      study. METHODS: We evaluated shoulder girdle motion (scapula, clavicle, and
      humerus) relative to the thorax of 14 shoulders from 8 whole cadavers after
      sequential sectioning of the AC and CC ligaments (trapezoid and conoid
      ligaments). An electromagnetic tracking device measured 3-dimensional kinematics
      of the scapula and clavicle during humerothoracic elevation in the coronal and
      sagittal planes and adduction in the horizontal plane. RESULTS: Sectioning of the
      AC ligament increased clavicular retraction during sagittal plane elevation and
      horizontal plane adduction. Sectioning of the trapezoid ligament decreased
      scapular external rotation during sagittal plane elevation and horizontal plane
      adduction. Sectioning of the conoid ligament decreased scapular posterior tilting
      during sagittal plane elevation and horizontal plane adduction. Acromioclavicular
      and CC ligament sectioning also delayed clavicular posterior rotation and
      increased clavicular upward rotation during coronal plane elevation. CONCLUSION:
      Our study revealed that AC and CC ligament disruption affected in vitro shoulder
      girdle kinematics in the whole-cadaver model. CLINICAL RELEVANCE: The results of
      this cadaveric study revealed that AC and CC ligament disruption could cause
      dyskinesis of the scapula and clavicle. The kinematic changes could be a
      potential source of pain and dysfunction in the shoulder with AC joint
      dislocation, and therefore surgical reconstruction may be indicated in certain
      patients.

PMID- 22967827
TI  - Microfracture for osteochondral lesions of the talus: a systematic review of
      reporting of outcome data.
AB  - BACKGROUND: Microfracture is recognized as a primary treatment strategy for
      osteochondral lesions of the talus up to 15 mm in size. The ability of
      fibrocartilage to withstand the mechanical loading of the joint over time is
      unknown. PURPOSE: The purpose of this study was to systematically review studies
      of microfracture for OLT and descriptively analyze the outcome data reported to
      determine whether it is consistent from one study to another and able to be
      pooled for systematic review. METHODS: A systematic electronic search was
      performed using the MEDLINE and EMBASE databases. Studies that were published
      between January 1966 and June 2011 were included in the review. Only studies that
      reported data specifically on microfracture for treatment of osteochondral
      lesions of the talus and written in English were included in this review.
      RESULTS: Twenty-four studies were included in this systematic review. The
      categories of general demographics and study design were generally well reported
      (each over 80% of studies). Patient history and patient-reported outcome data
      were reported less (55%-66%). Clinical variables (48%) and imaging data (39%)
      were the least reported in studies. CONCLUSION: There were gross inconsistencies
      and an underreporting of data between studies such that pooling was deemed
      impossible. A concerted effort must be made by investigators to ensure that there
      is adequate reporting of data in studies of microfracture treatment for OLT. A
      set of guidelines to assist surgeons in reporting data may be useful for future
      research.

PMID- 22967826
TI  - Longitudinal documentation of serum cartilage oligomeric matrix protein and
      patient-reported outcomes in collegiate soccer athletes over the course of an
      athletic season.
AB  - BACKGROUND: Serum cartilage oligomeric matrix protein (sCOMP) is a biomarker for
      cartilage degradation. Patient-reported outcomes (PRO) are used to document
      postinjury recovery and may be used to prospectively identify changes in the
      course of a season. It is unknown what effect intense, continuous physical
      activity has on sCOMP levels and PRO values in athletes over the duration of a
      soccer season. Hypothesis/ PURPOSE: The purpose of this study was to
      longitudinally document sCOMP levels and to determine whether changes in PROs
      occur in collegiate soccer athletes during a season. The hypotheses tested were
      that sCOMP levels and PRO scores would remain stable over the duration of the
      spring soccer season. STUDY DESIGN: Case series; level of evidence, 4. METHODS:
      Twenty-nine National Collegiate Athletic Association Division-I soccer athletes
      (18 men, 11 women; age, 19.6 +/- 1.2 years; height, 177.8 +/- 7.4 cm; mass, 73.8
      +/- 10.2 kg) participated in 3 (pre-[T(1)], mid-[T(2)], and postseason [T(3)])
      data collection sessions. Subjects were included if they were participants in the
      spring soccer season and were free of severe knee injury at the time of data
      collection. At each session, subjects completed PROs (Lysholm, International Knee
      Documentation Committee scores) before serum collection. RESULTS: For sCOMP
      (ng/mL), there was a significant effect for time, with significant increases at
      T(2) (1723.5 +/- 257.9, P < .001) and T(3) (1624.7 +/- 231.6, P = .002) when
      compared with T(1)(1482.9 +/- 217.9). For each of the PROs, there was a
      significant effect for time from T(1)-T(3), and at T(2)-T(3) for the IKDC.
      CONCLUSION: These data indicate sCOMP levels increased as athletes reported an
      increased level of function over time. However, the differences in sCOMP levels
      did not reach the calculated minimal detectable change (MDC) value and the
      differences in PRO scores did not reach previously calculated MDC values. It is
      unclear whether these increases in sCOMP levels were caused by an increase in
      cartilage matrix breakdown or turnover. Even though these elevations may not be
      clinically meaningful, this biomarker may have the potential to be used for
      future research studies investigating the effects of exercise on overall joint
      health in longitudinal studies. In addition, these results indicate fluctuations
      in sCOMP occur during a competitive season and must be taken into consideration
      for future biomarker studies.

PMID- 22967829
TI  - Transfer of suicide risk versus looking at suicides outside hospital in general.

PMID- 22967828
TI  - Ultrabithorax confers spatial identity in a context-specific manner in the
      Drosophila postembryonic ventral nervous system.
AB  - BACKGROUND: In holometabolous insects such as Drosophila melanogaster,
      neuroblasts produce an initial population of diverse neurons during embryogenesis
      and a much larger set of adult-specific neurons during larval life. In the
      ventral CNS, many of these secondary neuronal lineages differ significantly from
      one body segment to another, suggesting a role for anteroposterior patterning
      genes. RESULTS: Here we systematically characterize the expression pattern and
      function of the Hox gene Ultrabithorax (Ubx) in all 25 postembryonic lineages. We
      find that Ubx is expressed in a segment-, lineage-, and hemilineage-specific
      manner in the thoracic and anterior abdominal segments. When Ubx is removed from
      neuroblasts via mitotic recombination, neurons in these segments exhibit the
      morphologies and survival patterns of their anterior thoracic counterparts.
      Conversely, when Ubx is ectopically expressed in anterior thoracic segments,
      neurons exhibit complementary posterior transformation phenotypes. CONCLUSION:
      Our findings demonstrate that Ubx plays a critical role in conferring segment
      appropriate morphology and survival on individual neurons in the adult-specific
      ventral CNS. Moreover, while always conferring spatial identity in some sense,
      Ubx has been co-opted during evolution for distinct and even opposite functions
      in different neuronal hemilineages.

PMID- 22967830
TI  - Blue flags.

PMID- 22967831
TI  - Field studies using fish biomarker--how many fish are enough?
AB  - Significant efforts are invested in field studies using fish, and it is important
      to optimize the number of organisms collected to evaluate the possible impacts of
      contamination. This paper provides ecotoxicologists with the approximate numbers
      of fish needed to identify statistically significant differences among samples
      using physiological indices and biochemical markers of fish health. The numbers
      of fish to collect are reported for ethoxyresorufin-o-deethylase (EROD);
      ethoxycoumarin-o-deethylase (ECOD), serum sorbitol dehydrogenase (sSDH), stress
      proteins, gonadosomatic index, liver somatic index, condition factor, and biliary
      metabolites of polycyclic aromatic hydrocarbons. The number of fish to collect
      was as few as four for ECOD activity (with a power of 80%), but as high as 106
      for CF (with a power of 95%). Achieving statistical significance between sites
      does not help in the interpretation of the biological significance of a
      parameter, but well-planned field samplings will maximize the chances of
      correctly identifying areas of concern.

PMID- 22967833
TI  - Pharmacology and placental transport of 17-hydroxyprogesterone caproate in
      singleton gestation.
AB  - OBJECTIVE: The purpose of this study was to estimate pharmacokinetic parameters
      and to evaluate placental transport of 17-hydroxyprogesterone caproate (17-OHPC)
      in singleton gestation. STUDY DESIGN: Sixty-one women who received weekly
      injections of 17-OHPC underwent 2 pharmacokinetic studies at 20 + 0 to 24 + 6
      weeks' gestation (study 1) and 31 + 0 to 34 + 6 weeks' gestation (study 2); daily
      blood samples were obtained between injections. In 18 women, blood samples were
      obtained over a 28-day period beyond the last injection (extended study).
      Maternal and/or cord blood were obtained at delivery. RESULTS: The half-life
      (median +/- SD) of 17-OHPC was 16.2 +/- 6 days. Concentrations of 17-OHPC were
      higher during study 2 than during study 1. Body mass index affected maternal 17
      OHPC concentrations. Cord:maternal 17-OHPC concentration ratios averaged 0.2; 17
      OHPC was detectible in cord plasma 44 days after the last maternal injection.
      CONCLUSION: The apparent half-life of 17-OHPC is long, and pharmacokinetic
      parameters vary widely between subjects and are affected by maternal body mass
      index. The drug crosses the placental barrier.

PMID- 22967834
TI  - Proteases are associated with a minor fucoxanthin chlorophyll a/c-binding protein
      from the diatom, Chaetoceros gracilis.
AB  - We previously showed that most subunits in the oxygen-evolving photosystem II
      (PSII) preparation from the diatom Chaetoceros gracilis are proteolytically
      unstable. Here, we focused on identifying the proteases that cleave PSII subunits
      in thylakoid membranes. Major PSII subunits and fucoxanthin chlorophyll (Chl) a/c
      binding proteins (FCPs) were specifically degraded in thylakoid membranes. The
      PSI subunits, PsaA and PsaB, were slowly degraded, and cytochrome f was barely
      degraded. Using zymography, proteolytic activities for three metalloproteases
      (116, 83, and 75kDa) and one serine protease (156kDa) were detected in thylakoid
      membranes. Two FCP fractions (FCP-A and FCP-B/C) and a photosystem fraction were
      separated by sucrose gradient centrifugation using dodecyl maltoside-solubilized
      thylakoids. The FCP-A fraction featured enriched Chl c compared with the bulk of
      FCP-B/C. Zymography revealed that 116, 83, and 94kDa metalloproteases were mostly
      in the FCP-A fraction along with the 156kDa serine protease. When solubilized
      thylakoids were separated with clear-native PAGE, zymography detected only the
      83kDa metalloprotease in the FCP-A band. Because FCP-A is selectively associated
      with PSII, these FCP-A-associated metalloproteases and serine protease may be
      responsible for the proteolytic degradation of FCPs and PSII in thylakoid
      membranes.

PMID- 22967832
TI  - Deep brain stimulation induces BOLD activation in motor and non-motor networks:
      an fMRI comparison study of STN and EN/GPi DBS in large animals.
AB  - The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a
      powerful means of tracing brain circuitry and testing the modulatory effects of
      electrical stimulation on a neuronal network in vivo. The goal of this study was
      to trace DBS-induced global neuronal network activation in a large animal model
      by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We
      conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus
      (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analog of the
      primate globus pallidus interna (n=4). Using a normalized functional activation
      map for group analysis and the application of general linear modeling across
      subjects, we found that both STN and EN/GPi DBS significantly increased BOLD
      activation in the ipsilateral sensorimotor network (FDR<0.001). In addition, we
      found differential, target-specific, non-motor network effects. In each group the
      activated brain areas showed a distinctive correlation pattern forming a group of
      network connections. Results suggest that the scope of DBS extends beyond an
      ablation-like effect and that it may have modulatory effects not only on circuits
      that facilitate motor function but also on those involved in higher cognitive and
      emotional processing. Taken together, our results show that the swine model for
      DBS fMRI, which conforms to human implanted DBS electrode configurations and
      human neuroanatomy, may be a useful platform for translational studies
      investigating the global neuromodulatory effects of DBS.

PMID- 22967835
TI  - Vertebral strains during high speed, low amplitude cervical spinal manipulation.
      J Electromyogr Kinesiol (2012) http://dx.doi.org/10.1016/j.elekin.2012.03.005.

PMID- 22967836
TI  - Myoelectric activity along human gastrocnemius medialis: different spatial
      distributions of postural and electrically elicited surface potentials.
AB  - It has recently been shown that motor units in human medial gastrocnemius (MG),
      activated during standing, occupy relatively small territories along the muscle's
      longitudinal axis. Such organisation provides potential for different motor tasks
      to produce differing regional patterns of activity. Here, we investigate whether
      postural control and nerve electrical stimulation produce equal longitudinal
      activation patterns in MG. Myoelectric activity, at different proximal-distal
      locations of MG, was recorded using a linear electrode array. To ensure
      differences in signal amplitude between channels did not result from local,
      morphological factors two experimental protocols were completed: (i) quiet
      standing; (ii) electrical stimulation of the tibial nerve. Averaged, rectified
      values (ARVs) were calculated for each channel in each condition. The
      distribution of signals along electrode channels was described using linear
      regression and differences between protocols at each channel determined as the
      ratio between mean ARV from standing: stimulation protocols. Ratio values changed
      systematically across electrode channels in seven (of eight) participants, with
      larger values in distal channels. The distribution of ARV along MG therefore
      differed between experimental conditions. Compared to fibres of units activated
      during MG nerve stimulation, units activated during standing may have a tendency
      to be more highly represented in the distal muscle portion.

PMID- 22967837
TI  - Epidemiology of adolescent Salvia divinorum use in Canada.
AB  - BACKGROUND: Salvia divinorum is a potent, naturally occurring hallucinogen
      gaining popularity as a recreational drug in North America. To date, detailed
      epidemiologic information about the use of this substance among adolescents
      living outside the United States has been limited. This study provides
      information on the prevalence and correlates of Salvia divinorum use among
      adolesecents in Canada using a nationally representative sample. METHODS: Data
      were obtained from a representative sample of 42,179 Canadian adolescents aged 12
      17 years living across all 10 provinces who completed the Youth Smoking Survey in
      2008-09. RESULTS: Overall, 3.8% of adolescents reported using Salvia in the past
      year and 6.2% had used the substance in their lifetime. A conservative estimate
      suggests 23.2% of youth were repeat users. Salvia use was highest among youth in
      British Columbia and Quebec. Comparatively, the prevalence of 12-month Salvia use
      was higher than 12-month cocaine and amphetamine use but lower than 12-month
      ecstasy, cannabis, and other hallucinogen use. Correlates of Salvia use included
      older age, male gender, high available spending money, binge drinking, illicit
      drug use and smoking in fully adjusted models. Findings suggest low self-esteem
      may be an important correlate specific to the use of this substance among youth.
      CONCLUSIONS: Salvia divinorum use is prevalent among Canadian adolescents. Salvia
      may be a significant public health issue in Canada given it is readily available,
      under limited regulation, and little is known about the abuse liability of the
      substance, interactions with other substances, and potential complications from
      use.

PMID- 22967838
TI  - From the stressed adolescent to the anxious and depressed adult: investigations
      in rodent models.
AB  - Anxiety and depression are the most prevalent of the psychiatric disorders. The
      average age of onset of these disorders is in adolescence, and stressful
      experiences are recognized as an important pathway to such dysfunction. Until
      recently, however, most animal models of these disorders involved adult males. We
      provide a brief overview of anxiety and depression and the extent to which
      adolescent rodents are a valid model for their investigation, and briefly review
      the main measures of anxiety-like and depressive behaviour in rodents. The focus
      of the review is investigations in which adolescent rodents were exposed to
      chronic stressors, describing our research using social instability stress and
      that of other researchers using various social and non-social stressors. The
      evidence to date suggests stress in adolescence alters the trajectory of brain
      development, and particularly that of the hippocampus, increasing anxiety and
      depressive behaviour in adulthood. 

PMID- 22967839
TI  - Muller glia express rhodopsin in a mouse model of inherited retinal degeneration.
AB  - The Muller glial cells exhibit stem cell properties and express neuronal markers
      following experimentally induced retinal injury. However, it is not known whether
      Muller glia respond similarly to degenerative neuronal loss caused by genetic
      mutation. Here, we asked whether Muller cells dedifferentiate and express
      neuronal proteins in rd1 mouse, a naturally occurring mutant model of inherited
      retinal degeneration. Using immunohistochemistry and Western blotting, we studied
      expression patterns of glial fibrillary acidic protein (GFAP), nestin, rhodopsin,
      protein kinase C alpha (PKCalpha), beta-III-tubulin and recoverin in Muller glia.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to
      detect any rhodopsin mRNA in the rd1 mouse retina. We found that Muller cell
      processes in rd1 mouse hypertrophied and overexpressed GFAP as early as postnatal
      day (P)-14, features that were maintained throughout development and in the adult
      stage. Furthermore, Muller cells continued to express nestin, a progenitor cell
      marker, up to 6 months of age, raising the possibility that they remain
      undifferentiated for several months in rd1 mouse. We did not find nestin
      expression in Muller cells in 1-year-old rd1 mouse. Interestingly, Muller cell
      processes in rd1 mouse also expressed rhodopsin, a rod-specific protein. The
      rhodopsin expression in Muller cells was evident at P-21, and remained so up to
      at least 1 year of age. The expression of rhodopsin by Muller cells was further
      supported by our finding of the rhodopsin transcript in the 9-month-old rd1 mouse
      retina. We did not find the expression of PKCalpha, beta-III-tubulin or recoverin
      in Muller cells in adult rd1 mouse. These results suggested that Muller cells in
      rd1 mouse express proteins specific to retinal neurons that are the primary
      targets of the mutation in this mouse. Although the functional significance of
      rhodopsin expression by Muller cells is unclear, these results have implications
      for novel therapeutic strategies for retinal degeneration.

PMID- 22967840
TI  - Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to
      hippocampal structural and functional plasticity.
AB  - Glucocorticoids serve as key stress response hormones that facilitate stress
      coping. However, sustained glucocorticoid exposure is associated with adverse
      consequences on the brain, in particular within the hippocampus. Chronic
      glucocorticoid exposure evokes neuronal cell damage and dendritic atrophy,
      reduces hippocampal neurogenesis and impairs synaptic plasticity. Glucocorticoids
      also alter expression and signaling of the neurotrophin, brain-derived
      neurotrophic factor (BDNF). Since BDNF is known to promote neuroplasticity,
      enhance cell survival, increase hippocampal neurogenesis and cellular
      excitability, it has been hypothesized that specific adverse effects of
      glucocorticoids may be mediated by attenuating BDNF expression and signaling. The
      purpose of this review is to summarize the current state of literature examining
      the influence of glucocorticoids on BDNF, and to address whether specific effects
      of glucocorticoids arise through perturbation of BDNF signaling. We integrate
      evidence of glucocorticoid regulation of BDNF at multiple levels, spanning from
      the well-documented glucocorticoid-induced changes in BDNF mRNA to studies
      examining alterations in BDNF receptor-mediated signaling. Further, we delineate
      potential lines of future investigation to address hitherto unexplored aspects of
      the influence of glucocorticoids on BDNF. Finally, we discuss the current
      understanding of the contribution of BDNF to the modulation of structural and
      functional plasticity by glucocorticoids, in particular in the context of the
      hippocampus. Understanding the mechanistic crosstalk between glucocorticoids and
      BDNF holds promise for the identification of potential therapeutic targets for
      disorders associated with the dysfunction of stress hormone pathways.

PMID- 22967842
TI  - Effects of species differences on oocyte regulation of granulosa cell function.
AB  - The aims were to investigate whether oocyte-secreted growth factors from a high
      (i.e. rat) and low (i.e. sheep) ovulation rate species could stimulate (3)H
      thymidine incorporation in granulosa cells (GC) from antral follicles from the
      same or across species. Denuded oocytes (DO) were co-incubated with GC with or
      without specific antibodies to growth differentiating factor 9 (GDF9) or bone
      morphogenetic protein 15 (BMP15). Co-incubations of DO-GC from the same or across
      species significantly increased thymidine incorporation in GC with increasing
      numbers of DO. GDF9 immuno-neutralisation reduced thymidine incorporation in rat
      GC co-incubated with either rat or ovine DO and in ovine GC co-incubated with
      ovine or rat DO. BMP15 immuno-neutralisation only reduced thymidine incorporation
      when ovine DO were co-incubated with either ovine or rat GC. Western blotting of
      oocytes co-incubated with GC identified GDF9 and BMP15 proteins for sheep and
      GDF9 protein for rats in oocyte lysates and incubation media. With respect to rat
      BMP15, a promature protein was identified in the oocyte lysate but not in media.
      Expression levels of GDF9 relative to BMP15 mRNA in DO co-incubated with GC were
      highly correlated (R (2)=0.99) within both species. However, the expression
      ratios were markedly different for the rat and sheep (4.3 vs 1.0 respectively).
      We conclude that during follicular development, rat oocytes secrete little, if
      any, BMP15 and that GDF9 without BMP15 can stimulate proliferation of rat and
      ovine GC. In contrast, ovine oocytes secrete both BMP15 and GDF9, and both were
      found to stimulate proliferation in ovine and rat GC.

PMID- 22967841
TI  - Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial
      contractile dysfunction and apoptosis.
AB  - Alcohol intake is associated with myocardial contractile dysfunction and
      apoptosis although the precise mechanism is unclear. This study was designed to
      examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol
      induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair
      fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice
      started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for
      the remaining feeding duration. Cardiac function was assessed using
      echocardiographic and IonOptix systems. Western blot analysis was used to
      evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+)
      regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+)
      exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun
      NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1).
      Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased
      levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular
      Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis
      accompanied with increased phosphorylation of JNK and ASK-1, the effects were
      significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK
      1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced
      cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1
      signaling in ethanol-induced myocardial injury. Taken together, these findings
      suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis
      of alcoholic cardiomyopathy including myocardial contractile dysfunction,
      oxidative stress and apoptosis, possibly through activation of JNK and ASK-1
      signaling.

PMID- 22967843
TI  - Dynamic, but not static, pain sensitivity predicts exercise-induced muscle pain:
      covariation of temporal sensory summation and pain intensity.
AB  - Cross-section studies suggest that measures of pain sensitivity, derived from
      quantitative sensory testing (QST), are elevated in persons with chronic pain
      conditions. However, little is known about whether development of chronic pain is
      preceded by elevated pain sensitivity or pain sensitivity increases as a result
      of prolonged experience of pain. Here we used QST to test static (single
      suprathreshold stimuli) and dynamic (temporal sensory summation) pain processing
      of thermal stimuli. Muscle pain was induced using high-intensity exercise (DOMS).
      Multi-level modeling approaches determined the daily covariation among static and
      dynamic QST measures and pain intensity. Variation in responses to static pain
      sensitivity was not associated with pain intensity from DOMS while, in contrast,
      variation in dynamic pain sensitivity was positively associated with variation in
      pain intensity from DOMS. This finding supports the use of TSS as a marker of the
      central pain state and potentially as an appropriate measure for treatment
      monitoring.

PMID- 22967844
TI  - LRP1 expression in cerebral cortex, choroid plexus and meningeal blood vessels:
      relationship to cerebral amyloid angiopathy and APOE status.
AB  - APOE genotype is a risk factor for Alzheimer's disease (AD) and cerebral amyloid
      angiopathy (CAA). The risk and severity of CAA increase with possession of APOE
      epsilon4, whereas APOE epsilon2 increases the risk of vessel rupture. Uptake of
      Abeta by cerebrovascular smooth muscle cells (CVSMCs) is mediated by low-density
      lipoprotein receptor-related protein-1 (LRP1). To determine whether APOE
      influences CAA by altering LRP1 expression, particularly by CVSMCs, we analysed
      APOE genotype, CAA severity, and LRP1 levels in post-mortem cerebral cortex,
      choroid plexus and meningeal vessels. LRP1 mRNA and protein were not related to
      CAA severity and presence. LRP1 mRNA was increased in meningeal vessels, but not
      cortex or choroid plexus, in AD and in association with APOE epsilon4, and was
      decreased in association with APOE epsilon3. In brains with CAA, APOE epsilon2
      was associated with decreased LRP1 protein in meningeal vessels, and epsilon3
      with increased LRP1 in choroid plexus. These findings suggest that APOE may
      influence the severity of CAA through altered expression of LRP1.

PMID- 22967845
TI  - Neuropeptide complexity in the crustacean central olfactory pathway:
      immunolocalization of A-type allatostatins and RFamide-like peptides in the brain
      of a terrestrial hermit crab.
AB  - BACKGROUND: In the olfactory system of malacostracan crustaceans, axonal input
      from olfactory receptor neurons associated with aesthetascs on the animal's first
      pair of antennae target primary processing centers in the median brain, the
      olfactory lobes. The olfactory lobes are divided into cone-shaped synaptic areas,
      the olfactory glomeruli where afferents interact with local olfactory
      interneurons and olfactory projection neurons. The local olfactory interneurons
      display a large diversity of neurotransmitter phenotypes including biogenic
      amines and neuropeptides. Furthermore, the malacostracan olfactory glomeruli are
      regionalized into cap, subcap, and base regions and these compartments are
      defined by the projection patterns of the afferent olfactory receptor neurons,
      the local olfactory interneurons, and the olfactory projection neurons. We wanted
      to know how neurons expressing A-type allatostatins (A-ASTs; synonym dip
      allatostatins) integrate into this system, a large family of neuropeptides that
      share the C-terminal motif -YXFGLamide. RESULTS: We used an antiserum that was
      raised against the A-type Diploptera punctata (Dip)-allatostatin I to analyse the
      distribution of this peptide in the brain of a terrestrial hermit crab, Coenobita
      clypeatus (Anomura, Coenobitidae). Allatostatin A-like immunoreactivity (ASTir)
      was widely distributed in the animal's brain, including the visual system,
      central complex and olfactory system. We focussed our analysis on the central
      olfactory pathway in which ASTir was abundant in the primary processing centers,
      the olfactory lobes, and also in the secondary centers, the hemiellipsoid bodies.
      In the olfactory lobes, we further explored the spatial relationship of olfactory
      interneurons with ASTir to interneurons that synthesize RFamide-like peptides. We
      found that these two peptides are present in distinct populations of local
      olfactory interneurons and that their synaptic fields within the olfactory
      glomeruli are also mostly distinct. CONCLUSIONS: We discuss our findings against
      the background of the known neurotransmitter complexity in the crustacean
      olfactory pathway and summarize what is now about the neuronal connectivity in
      the olfactory glomeruli. A-type allatostatins, in addition to their localization
      in protocerebral brain areas, seem to be involved in modulating the olfactory
      signal at the level of the deutocerebrum. They contribute to the complex local
      circuits within the crustacean olfactory glomeruli the connectivity within which
      as yet is completely unclear. Because the glomeruli of C. clypeatus display a
      distinct pattern of regionalization, their olfactory systems form an ideal model
      to explore the functional relevance of glomerular compartments and diversity of
      local olfactory interneurons for olfactory processing in crustaceans.

PMID- 22967847
TI  - [Not Available].

PMID- 22967846
TI  - Antagonists of GPR35 display high species ortholog selectivity and varying modes
      of action.
AB  - Variation in pharmacology and function of ligands at species orthologs can be a
      confounding feature in understanding the biology and role of poorly characterized
      receptors. Substantial selectivity in potency of a number of GPR35 agonists has
      previously been demonstrated between human and rat orthologs of this G protein
      coupled receptor. Via a bioluminescence resonance energy transfer-based assay of
      induced interactions between GPR35 and beta-arrestin-2, addition of the mouse
      ortholog to such studies indicated that, as for the rat ortholog, murine GPR35
      displayed very low potency for pamoate, whereas potency for the reference GPR35
      agonist zaprinast was intermediate between the rat and human orthologs. This
      pattern was replicated in receptor internalization and G protein activation
      assays. The effectiveness and mode of action of two recently reported GPR35
      antagonists, methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4
      difluorophenyl)pyrazole-4-carboxylate (CID-2745687) and 2-hydroxy-4-[4-(5Z)-5
      [(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3
      yl]butanoylamino)benzoic acid (ML-145), were investigated. Both CID-2745687 and
      ML-145 competitively inhibited the effects at human GPR35 of cromolyn disodium
      and zaprinast, two agonists that share an overlapping binding site. By contrast,
      although ML-145 also competitively antagonized the effects of pamoate, CID
      2745687 acted in a noncompetitive fashion. Neither ML-145 nor CID-2745687 was
      able to effectively antagonize the agonist effects of either zaprinast or
      cromolyn disodium at either rodent ortholog of GPR35. These studies demonstrate
      that marked species selectivity of ligands at GPR35 is not restricted to agonists
      and considerable care is required to select appropriate ligands to explore the
      function of GPR35 in nonhuman cells and tissues.

PMID- 22967848
TI  - Basic consensus document on late-onset hypogonadism.
AB  - One of the most important elements in men's live is the ability to engage in
      normal sexual activity; loss of this activity has always been considered
      especially important. The relationship between sexual activity, as well as other
      masculine characteristics, and the testicles has been well known since ancient
      times and has been related to the slow decrease in testosterone secretion with
      advanced age. Male hypogonadism is one of the most frequent and under-diagnosed
      endocrine diseases. Several terms have been proposed to refer to clinical
      situations caused by the age-related decline in male gonadal function; currently,
      the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a
      clinical and biochemical syndrome associated with advanced age (in men),
      characterized by typical symptoms and reduced serum testosterone concentrations,
      which can affect multiple organs and systems and reduce quality of life. This
      syndrome can be treated and the alterations produced can be reversed. To achieve
      this, a diagnostic protocol that approaches the multiple factors related to the
      risks and benefits of treatment is required.

PMID- 22967849
TI  - Clinical practice guideline for hypotalamic-pituitary disturbances in pregnancy
      and the postpartum period.
AB  - During pregnancy, the body undergoes a major adaptation process as a result of
      the interaction between mother, placenta and fetus. Major anatomical and
      histological changes are produced in the pituitary, with an increase of up to 40%
      in the size of the gland. There are wide variations in the function of the
      hypothalamus-pituitary-thyroid axis that effect iodine balance, the overall
      activity of the gland, as well as transport of thyroid hormones in plasma and
      peripheral metabolism of thyroid hormones. The incidence of goiter and thyroid
      nodules increases throughout pregnancy. The management of differentiated thyroid
      carcinoma should be individually tailored according to tumoral type and pregnancy
      stage. Given the effects of hypothyroidism on fetal development, both the
      diagnosis and appropriate therapeutic management of thyroid hypofunction are
      essential. The most important modification to the hypothalamus-pituitary-adrenal
      axis during pregnancy is the rise in serum cortisol levels due to an increase in
      cortisol-binding proteins. Although Cushing's syndrome during pregnancy is
      infrequent, both diagnosis and treatment of this disorder are especially
      difficult. Adrenal insufficiency during pregnancy does not substantially differ
      from that occurring outside pregnancy. However, postpartum pituitary necrosis
      (Sheehan's syndrome) is a well-known complication that occurs after delivery and,
      together with lymphocytic hypophysitis, constitutes the most frequent cause of
      adrenal insufficiency. The management of prolactinoma during pregnancy requires
      suppression of dopaminergic agonists and their reintroduction if there is tumoral
      growth. Notable among the neuropituitary disorders that can occur throughout
      pregnancy is diabetes insipidus, which occurs as a consequence of increased
      vasopressinase activity.

PMID- 22967850
TI  - Clinical practice guideline for the diagnosis and treatment of hypophysitis.
AB  - Hypophysitis are a group of inflammatory lesions affecting the pituitary gland
      and pituitary stalk. These lesions should be included in the differential
      diagnosis of sellar masses. There are three types of primary hypophysitis:
      lymphocytic, granulomatous and xanthomatous. Lymphocytic hypophysitis is the most
      frequent form of chronic pituitary inflammation and is believed to have an
      autoimmune origin. This form characteristically affects women during the
      peripartum, with diverse types of pituitary deficiency, especially ACTH
      deficiency, and frequently there are other associated autoimmune processes.
      Lymphocytic hypophysitis can affect the anterior pituitary only, the infundibular
      stalk and posterior lobe of the pituitary (infundibuloneurohypophysitis), or the
      entire pituitary (panhypophysitis). Clinically, lymphocytic hypophysitis can
      manifest with compression symptoms, hypopituitarism, diabetes insipidus or
      hyperprolactinemia. The imaging technique of choice is magnetic resonance
      imaging, which helps to characterize the sellar lesion. Treatment includes
      replacement of the functional pituitary deficiency and the use of
      corticosteroids, generally at high doses. Surgical treatment is reserved for
      patients unresponsive to conservative therapy. Granulomatous hypophysitis can be
      of known etiology, whether infectious (currently highly infrequent) or non
      infectious (ruptured Rathke's cyst, etc.). Granulomatous hypophysitis of unknown
      etiology is manifested by the presence of idiopathic granulomas. Xanthomatous
      hypophysitis is characterized by a histiocytic infiltrate with cystic
      characteristics on imaging. Secondary hypophysitis is due to pituitary
      inflammation caused by surrounding lesions or can form part of systemic diseases.

PMID- 22967851
TI  - Current situation of hospital-based endocrinology and clinical nutrition in
      Spain.
AB  - In 2006, the Healthcare Commission of Spanish Society of Endocrinology and
      Nutrition did a survey in order to know the actual situation of endocrinology and
      clinical nutrition healthcare in Public Sanitary Systems in Spain. The survey has
      been more extensive than the last and it has taken up number and geographical
      distribution of specialists in Spain in addition to data about clinical
      assistance. The mean of public hospitals with endocrinologist participation has
      been 50%.

PMID- 22967852
TI  - Prospective study of restless legs syndrome and coronary heart disease among
      women.
AB  - BACKGROUND: Previous cross-sectional studies suggested a positive association
      between restless legs syndrome (RLS) and coronary heart disease (CHD). This
      observation was not confirmed by subsequent prospective studies. However, these
      prospective studies did not take into account the duration of RLS symptoms.
      Therefore, we prospectively examined whether RLS was associated with an increased
      risk of CHD in women who participated in the Nurses' Health Study, taking into
      account the duration of RLS symptoms. METHODS AND RESULTS: A total of 70 977
      women (mean age, 67 years) who were free of CHD and stroke at baseline (2002)
      were followed up until 2008. Physician-diagnosed RLS was collected via
      questionnaire. CHD was defined as nonfatal myocardial infarction or fatal CHD.
      Women with RLS at baseline had a marginally higher risk of developing CHD
      (multivariable-adjusted hazard ratio, 1.46; 95% confidence interval, 0.97-2.18)
      compared with women without RLS. The risk was dependent on duration of symptoms:
      0.98 (95% confidence interval, 0.44-2.19) for women with RLS for <3 years and
      1.72 (95% confidence interval, 1.09-2.73) for women with RLS for >=3 years (P
      trend=0.03). The multivariable-adjusted hazard ratios of women with RLS for >=3
      years were 1.80 (95% confidence interval, 1.07-3.01) for nonfatal myocardial
      infarction and 1.49 (95% confidence interval, 0.55-4.04) for fatal CHD relative
      to women without RLS. CONCLUSIONS: We observed that women with RLS for at least 3
      years had an elevated risk of CHD. These results suggest that RLS or RLS
      associated conditions may contribute to the origin of cardiovascular disease.

PMID- 22967853
TI  - Efficacy of temporary positive expiratory pressure (TPEP) in patients with lung
      diseases and chronic mucus hypersecretion. The UNIKO(r) project: a multicentre
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether temporary positive expiratory pressure provides
      benefit in patients with lung diseases and chronic hypersecretion. DESIGN: Single
      blind multicentre randomized trial. SETTING: Five Italian rehabilitation centres.
      PARTICIPANTS: Ninety-eight patients with chronic obstructive pulmonary disease
      and/or chronic bronchitis (n=78), or bronchiectasis (n=20), with a peak cough
      expiratory flow >150 l/min and sputum production >30 ml/day, randomly included
      into two treatment groups. INTERVENTIONS: For 10 consecutive days, the active
      group performed twice a day 20-minute cycles of manually assisted breathing
      techniques in sequence with the addition of 15 minutes of temporary positive
      expiratory pressure, while the control group was treated by manually assisted
      breathing techniques alone. MEASURES: Within and between group changes of
      arterial oxygenation index, lung volumes and respiratory muscles strength were
      recorded at enrolment and after 3 and 10 treatment sessions. Pre-to-post
      treatment change of sputum volume and bronchial encumbrance (Delta-visual analog
      scale), sputum density and purulence were compared daily within the study period.
      RESULTS: No significant changes were recorded for the oxygenation index, while
      dynamic lung volumes and respiratory muscle strength significantly (P <0.05)
      improved in the active group. The group comparison analysis of the pre-to-post
      change showed that inspiratory capacity was significantly higher in the active
      than in the control group (+19.5% and +2.2%, P=0.044) at day 10. A greater
      improvement in Delta-visual analog scale was recorded in the active group at day
      3 and 8. CONCLUSIONS: These preliminary data suggest that temporary positive
      expiratory pressure improves lung volumes and speeds up the improvement of
      bronchial encumbrance in patients with lung diseases and hypersecretion.

PMID- 22967854
TI  - Computational modeling of apoptotic signaling pathways induced by cisplatin.
AB  - BACKGROUND: Apoptosis is an essential property of all higher organisms that
      involves extremely complex signaling pathways. Mathematical modeling provides a
      rigorous integrative approach for analyzing and understanding such intricate
      biological systems. RESULTS: Here, we constructed a large-scale, literature-based
      model of apoptosis pathways responding to an external stimulus, cisplatin. Our
      model includes the key elements of three apoptotic pathways induced by cisplatin:
      death receptor-mediated, mitochondrial, and endoplasmic reticulum-stress
      pathways. We showed that cisplatin-induced apoptosis had dose- and time-dependent
      characteristics, and the level of apoptosis was saturated at higher
      concentrations of cisplatin. Simulated results demonstrated that the effect of
      the mitochondrial pathway on apoptosis was the strongest of the three pathways.
      The cross-talk effect among pathways accounted for approximately 25% of the total
      apoptosis level. CONCLUSIONS: Using this model, we revealed a novel mechanism by
      which cisplatin induces dose-dependent cell death. Our finding that the level of
      apoptosis was affected by not only cisplatin concentration, but also by cross
      talk among pathways provides in silico evidence for a functional impact of system
      level characteristics of signaling pathways on apoptosis.

PMID- 22967855
TI  - Effect of common metal ions on the rate of degradation of 4-nitrophenol by a
      laccase-Cu2+ synergistic system.
AB  - Various metal ions are present in industrial wastewater. In this study, the role
      of Cu(2+) in pollutant degradation by laccase and the effect of common metal ions
      such as Na(+), K(+), Ca(2+), Mg(2+), Zn(2+), Hg(2+), Mn(2+), Fe(2+), Co(2+),
      Ni(2+), Fe(3+), and Al(3+) on the degradation velocity of the laccase-Cu(2+)
      synergistic system using 4-nitrophenol as the target pollutant were investigated.
      The results show that the laccase-Cu(2+) system achieved a higher degradation
      velocity than the system without Cu(2+). The activity of the laccase-Cu(2+)
      synergistic system was inhibited when a monovalent metal ion (Na(+) or K(+)) was
      added into the system regardless of the concentration. The addition of relatively
      low concentrations of any divalent metal ions also resulted in inhibition of the
      activity. However, increasing concentrations of Ca(2+) or Fe(2+) increased the
      rate of degradation of 4-nitrophenol by the laccase-Cu(2+) system, whereas
      increasing concentrations of other divalent metal ions suppressed the system. The
      inhibition effect of the added trivalent metal ions (Al(3+) or Fe(3+)) was
      significant during the entire process, indicating that these trivalent metal ions
      can be a serious obstacle to the activity of the laccase-Cu(2+) synergistic
      system.

PMID- 22967856
TI  - Seed storage at elevated partial pressure of oxygen, a fast method for analysing
      seed ageing under dry conditions.
AB  - BACKGROUND AND AIMS: Despite differences in physiology between dry and relative
      moist seeds, seed ageing tests most often use a temperature and seed moisture
      level that are higher than during dry storage used in commercial practice and
      gene banks. This study aimed to test whether seed ageing under dry conditions can
      be accelerated by storing under high-pressure oxygen. methods: Dry barley
      (Hordeum vulgare), cabbage (Brassica oleracea), lettuce (Lactuca sativa) and
      soybean (Glycine max) seeds were stored between 2 and 7 weeks in steel tanks
      under 18 MPa partial pressure of oxygen. Storage under high-pressure nitrogen gas
      or under ambient air pressure served as controls. The method was compared with
      storage at 45  degrees C after equilibration at 85 % relative humidity and long
      term storage at the laboratory bench. Germination behaviour, seedling morphology
      and tocopherol levels were assessed. KEY RESULTS: The ageing of the dry seeds was
      indeed accelerated by storing under high-pressure oxygen. The morphological
      ageing symptoms of the stored seeds resembled those observed after ageing under
      long-term dry storage conditions. Barley appeared more tolerant of this storage
      treatment compared with lettuce and soybean. Less-mature harvested cabbage seeds
      were more sensitive, as was the case for primed compared with non-primed lettuce
      seeds. Under high-pressure oxygen storage the tocopherol levels of dry seeds
      decreased, in a linear way with the decline in seed germination, but remained
      unchanged in seeds deteriorated during storage at 45  degrees C after
      equilibration at 85 % RH. CONCLUSIONS: Seed storage under high-pressure oxygen
      offers a novel and relatively fast method to study the physiology and
      biochemistry of seed ageing at different seed moisture levels and temperatures,
      including those that are representative of the dry storage conditions as used in
      gene banks and commercial practice.

PMID- 22967857
TI  - Predictive significance of the overvaluation of shape/weight in obese patients
      with binge eating disorder: findings from a randomized controlled trial with 12
      month follow-up.
AB  - BACKGROUND: Undue influence of body shape or weight on self-evaluation - referred
      to as overvaluation - is considered a core feature across eating disorders, but
      is not a diagnostic requirement for binge eating disorder (BED). This study
      examined the concurrent and predictive significance of overvaluation of
      shape/weight in obese patients with BED participating in a randomized clinical
      trial testing cognitive behavioral therapy (CBT) and behavioral weight loss
      (BWL). Method A total of 90 participants were randomly assigned to 6-month group
      treatments of CBT or BWL. Assessments were performed at baseline, throughout- and
      post-treatment, and at 6- and 12-month follow-ups after completing treatments
      with reliably administered semi-structured interviews and established measures.
      RESULTS: Participants categorized with overvaluation (n = 52, 58%) versus without
      overvaluation (n = 38, 42%) did not differ significantly in demographic features
      (age, gender and ethnicity), psychiatric co-morbidity, body mass index or binge
      eating frequency. The overvaluation group had significantly greater levels of
      eating disorder psychopathology and poorer psychological functioning (higher
      depression and lower self-esteem) than the non-overvaluation group. Overvaluation
      of shape/weight significantly predicted non-remission from binge eating and
      higher frequency of binge eating at the 12-month follow-up, even after adjusting
      for group differences in depression and self-esteem levels. CONCLUSIONS: Our
      findings suggest that overvaluation does not simply reflect concern commensurate
      with being obese or more frequent binge eating, but also is strongly associated
      with heightened eating-related psychopathology and psychological distress, and
      has negative prognostic significance for longer-term treatment outcomes.
      Overvaluation of shape/weight warrants consideration as a diagnostic specifier
      for BED as it provides important information about severity and treatment
      outcome.

PMID- 22967858
TI  - Non-human primate FOG develops with advanced parkinsonism induced by MPTP
      Treatment.
AB  - Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and
      other forms of parkinsonism. The anatomical or pathophysiological correlates are
      poorly understood largely due to the lack of a well-established animal model.
      Here we studied whether FOG is reproduced in the non-human primate (NHP) model of
      PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus
      Macaca, n=29) were examined for the development of FOG, and the leg movements
      were recorded with accelerometry. The relationships between developing FOG and
      the animals' characteristics, the MPTP treatments, and the modeled outcomes were
      determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting
      similar characteristics to those seen in PD patients. In addition, FOG episodes
      in the monkey were accompanied by leg trembling with the typical duration (2-10s)
      and frequency (~7 Hz). The development of NHP FOG was significantly associated
      with the severity of parkinsonism, as shown by high motor disability scores (>=
      20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively).
      Differences in demographics and MPTP treatments (doses, treatment duration, etc.)
      had no influence on NHP FOG occurrence, with the exception of gender that showed
      FOG predominance in males (p=0.03). The unique features of FOG in PD can be
      replicated in severely parkinsonian macaques, and this represents the first
      description of a FOG animal model.

PMID- 22967860
TI  - Grand rounds and a visiting professorship program in a department of radiology:
      how we do it.
AB  - We discuss the benefits of maintaining an active, rigorous, and highly structured
      grand rounds (GR) program in an academic radiology department. These benefits
      include education for faculty (continuing medical education), fellows, and
      residents and a venue for building collaboration and camaraderie within the
      department and institution, while also allowing for building ties with the
      radiology community at large. In addition, we illustrate how to build and sustain
      a dynamic GR program based on our collective 6-year experience in running such a
      program at our institution that has offered more than 180 GR and hosted more than
      90 visiting professors during this period. Maintaining such a program requires
      infrastructure, financial support, careful planning, and considerable effort. We
      believe that this article can serve as a "how-to" guide or framework to initiate
      and maintain such a program.

PMID- 22967859
TI  - Molecular cloning, recombinant expression and antibacterial activity analysis of
      hepcidin from Simensis crocodile (Crocodylus siamensis).
AB  - Hepcidin, a cysteine-rich cationic antibacterial peptide, plays an important role
      in human defense against pathogen infection. However, its role in reptile immune
      response and whether it is involved in antibacterial immune have not yet been
      proven. In order to study the antibacterial activity of Crocodylus siamensis
      hepcidin (Cshepc), a common reptile which lives in topic region of Southeast
      Asia, a cDNA sequence of Cshepc was cloned, which included an open reading frame
      (ORF) of 300 bp encoding a 99 amino acid preprohepcidin. Cshepc has eight
      cysteines formed four conserved disulfide bridges, similarly to that of human's.
      Sequence analysis showed that Cshepc mature peptide was more conserved than that
      of preprohepcidin. Tissue expression analysis indicated that Cshepc transcripts
      were highly expressed in the liver, muscle and heart of C. siamensis. Recombinant
      expressed hepcidin could significantly inhibit the growth of the Gram-negative
      bacteria Escherichia coli and Aeromonas sobria as well as the Gram-positive
      bacterium Staphylococcus aureus, and Bacillus subtilis in vitro, suggesting that
      Cshepc, like human hepcidin could play a role in the antibacterial function in
      hosts innate immune response.

PMID- 22967862
TI  - Foveal microstructure and functional parameters in lamellar macular hole.
AB  - PURPOSE: To evaluate the morphologic features of the photoreceptor layer (by
      spectral-domain optical coherence tomography) and functional parameters in
      patients with a lamellar macular hole. DESIGN: Prospective, multicenter,
      observational case series. METHODS: Fifty-four patients with lamellar macular
      hole were enrolled in the study. All patients underwent a complete ophthalmologic
      examination, including best-corrected visual acuity (BCVA) testing, MP1
      microperimetry, and spectral-domain optical coherence tomography. For each
      patient, 2 experienced masked observers evaluated the integrity of photoreceptor
      inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM)
      line. RESULTS: Spectral-domain optical coherence tomography analysis showed
      complete integrity of the IS/OS junction and ELM line in 40 eyes (group A),
      partial or complete disruption of the IS/OS junction with an intact ELM line in 8
      eyes (group B), and an alteration of both IS/OS junction and ELM line in 6 eyes
      (group C). Mean BCVA, total retinal sensitivity, and fixation stability were
      significantly better in groups A and B than in group C (both P < .05, Tukey
      Kramer test), whereas there was no significant difference between groups A and B.
      Mean central retinal sensitivity was significantly different among all 3 groups
      (all P < .05, Tukey-Kramer test). The grade of integrity of the foveal
      photoreceptor layer was correlated significantly with mean BCVA (r = -0.57; P <
      .001), mean central retinal sensitivity (r = 0.52; P < .001), and total retinal
      sensitivity (r = 0.44; P < .001). CONCLUSIONS: In lamellar macular hole, the
      morphologic features of the foveal photoreceptor layer consistently are
      correlated with BCVA and central retinal sensitivity. Preservation of the ELM is
      related to the maintenance of visual acuity.

PMID- 22967861
TI  - Molecular details of membrane fluidity changes during apoptosis and relationship
      to phospholipase A(2) activity.
AB  - Secretory phospholipase A(2) exhibits much greater activity toward apoptotic
      versus healthy cells. Various plasma membrane changes responsible for this
      phenomenon have been proposed, including biophysical alterations described as
      "membrane fluidity" and "order." Understanding of these membrane perturbations
      was refined by applying studies with model membranes to fluorescence measurements
      during thapsigargin-induced apoptosis of S49 cells using probes specific for the
      plasma membrane: Patman and trimethylammonium-diphenylhexatriene. Alterations in
      emission properties of these probes corresponded with enhanced susceptibility of
      the cells to hydrolysis by secretory phospholipase A(2). By applying a
      quantitative model, additional information was extracted from the kinetics of
      Patman equilibration with the membrane. Taken together, these data suggested that
      the phospholipids of apoptotic membranes display greater spacing between adjacent
      headgroups, reduced interactions between neighboring lipid tails, and increased
      penetration of water among the heads. The phase transition of artificial bilayers
      was used to calibrate quantitatively the relationship between probe fluorescence
      and the energy of interlipid interactions. This analysis was applied to results
      from apoptotic cells to estimate the frequency with which phospholipids protrude
      sufficiently at the membrane surface to enter the enzyme's active site. The data
      suggested that this frequency increases 50-100-fold as membranes become
      susceptible to hydrolysis during apoptosis.

PMID- 22967863
TI  - Minocycline controls clinical outcomes and inflammatory cytokines in moderate and
      severe meibomian gland dysfunction.
AB  - PURPOSE: To assess clinical outcomes and tear cytokine levels in patients with
      moderate and severe meibomian gland dysfunction (MGD) after treatment with oral
      minocycline and artificial tears versus artificial tears only. DESIGN:
      Prospective, randomized clinical trial. METHODS: Sixty eyes of 60 patients with
      stage 3 or 4 meibomian gland dysfunction were enrolled. We evaluated the tear
      film break-up time, Schirmer test results, corneal and conjunctival fluorescein
      staining results, biomicroscopic examination results of lid margins and meibomian
      glands, and tear cytokine levels before and after 1 month and 2 months of oral
      minocycline and artificial tears (group 1) or artificial tears only (group 2).
      Tear samples were collected and analyzed using a BD Cytometric Bead Array (BD
      Bioscience, San Jose, California, USA) for detection of interleukin (IL)-1beta,
      IL-6, IL-7, IL-8, IL-12p70, IL-17alpha, interferon-gamma, tumor necrosis factor
      alpha, and monocyte chemotactic protein-1. The Wilcoxon signed-rank test, Mann
      Whitney U test, generalized linear model, and linear mixed model were performed.
      RESULTS: Patients in group 1 showed statistically significant improvement in all
      clinical signs and symptoms after 1 month and 2 months of treatment. Patients of
      group 1 showed more significant improvement compared with those in group 2.
      Patients in group 1 also showed statistically significant reductions in IL-6, IL
      1beta, IL-17alpha, tumor necrosis factor-alpha, and IL-12p70 after 2 months of
      treatment. CONCLUSIONS: Oral minocycline can provide clinical benefits in
      treating moderate and severe meibomian gland dysfunction by reducing inflammatory
      cytokine levels.

PMID- 22967864
TI  - Reproducibility of optical coherence tomography measurements in children.
AB  - PURPOSE: To determine the interobserver and intraobserver reproducibility of a
      Fourier-domain optical coherence tomography device (Cirrus HD OCT; Carl Zeiss
      Meditec, Dublin, California, USA) in normal pediatric eyes. DESIGN: Prospective
      cross-sectional study. METHODS: One hundred healthy children were recruited
      prospectively and consecutively. Only 1 randomly chosen eye per subject was
      included in the study. The eye underwent 3 scans centered on the optic disc and
      another 3 scans centered on the macula that were acquired by a single operator. A
      fourth examination was performed by a second operator. Interobserver and
      intraobserver reproducibility were described by intraclass correlation
      coefficients (ICCs) and coefficients of variation (COVs). RESULTS: The mean age
      was 9.15 years (range, 6.22 to 11.31 years; standard deviation, 1.05 years). Mean
      retinal nerve fiber layer thickness was 99.53 MUm (standard deviation, 10.10
      MUm), and mean macular thickness was 282.91 MUm (standard deviation, 11.83 MUm).
      All the parameters evaluated were highly reproducible. Intraobserver COVs of the
      retinal nerve fiber layer measurements ranged from 2.24% to 5.52%, and the COV of
      macular thickness was 0.97%. The intraclass correlation coefficient was greater
      than 0.8 for all the parameters. The interobserver COV ranged from 2.23% to
      5.18%, and the COV of macular thickness was 0.82%. In all the evaluated
      parameters, the intraclass correlation coefficient was more than 0.75.
      Repeatability was slightly better in children older than 10 years than in
      children younger than 9 years. CONCLUSIONS: Retinal nerve fiber layer and macular
      measurements obtained by Fourier-domain optical coherence tomography showed good
      repeatability for healthy eyes in the pediatric population. Cirrus HD OCT
      examinations of the retina are reliable in children.

PMID- 22967865
TI  - Clinical outcomes of phototherapeutic keratectomy in eyes with Thiel-Behnke
      corneal dystrophy.
AB  - PURPOSE: To investigate the functional and morphologic midterm outcome of
      phototherapeutic keratectomy (PTK) for Thiel-Behnke corneal dystrophy diagnosed
      by gene-mutation analysis. DESIGN: Retrospective, single-center clinical study.
      METHODS: Between July 2001 and May 2010, 10 consecutive PTKs were performed in 10
      eyes of 5 patients (2 male, 3 female; mean age: 55 +/- 13 years) with
      superficially accentuated opacities caused by Thiel-Behnke corneal dystrophy and
      were followed up for at least 12 months (range: 12-108 months). Main outcome
      measures included (1) best-corrected visual acuity (BCVA), (2) uncorrected visual
      acuity (UCVA), (3) spherical equivalent, and (4) recurrence rate. The probability
      of recurrence of Thiel-Behnke corneal dystrophy after PTK was calculated using
      the Kaplan-Meier method for survival analysis. RESULTS: The p.Arg555Gln mutation
      was found within the TGFBI gene in all 5 patients. Average logarithm of minimal
      angle of resolution (logMAR) BCVA change was -0.55 +/- 0.26. Average logarithm
      UCVA change was -0.54 +/- 0.31. In 5 of the 10 eyes, recurrence of central
      superficial opacification was clinically identified during the follow-up periods,
      and in 4 of those 5 eyes, the level of the recurrence was so significant that the
      visual acuity was reduced more than 2 lines. The maximum follow-up period of the
      1 eye without significant post-PTK recurrence was 108 months. CONCLUSIONS: PTK is
      a successful therapy for Thiel-Behnke corneal dystrophy, and results in midterm
      stable visual acuity and corneal transparency. Unlike in Reis-Bucklers corneal
      dystrophy cases, PTK delays the need for more invasive surgical intervention in
      Thiel-Behnke corneal dystrophy.

PMID- 22967866
TI  - Comparative cost-effectiveness analysis of descemet stripping automated
      endothelial keratoplasty versus penetrating keratoplasty in the United States.
AB  - PURPOSE: To perform a comparative cost-effectiveness analysis of Descemet
      stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty
      (PK) for corneal endothelial disease. DESIGN: Retrospective cost-effectiveness
      analysis. METHODS: This cost-effectiveness analysis was performed from a third
      party payer perspective with a 5-year time horizon. Probabilities of outcomes and
      complications of each of the procedures were calculated based on review of the
      published literature. A model was constructed to compare the costs and utilities
      associated with DSAEK and PK. Costs of donor tissue preparation, surgery, follow
      up, postoperative complications, and procedures were considered. Utility values
      were based on quality-adjusted life years associated with visual acuity outcomes.
      Both costs and utilities were discounted at 3% per year. Sensitivity analyses
      were performed on key model inputs. RESULTS: Base case analysis found DSAEK to be
      less costly compared with PK ($9362 vs $10 239), with greater utility (3.15 vs
      2.47 quality-adjusted life years). Sensitivity analyses revealed that even at
      graft failure rates for DSAEK approaching the rates for PK, DSAEK would still
      reduce costs. Varying the dislocation rate in our model showed that even at
      dislocation rates approaching 50%, DSAEK remained less costly. Further, with
      DSAEK rejection rates as high as 28%, DSAEK would remain a dominant procedure
      over PK. CONCLUSIONS: Comparative cost-effectiveness analysis of DSAEK versus PK
      indicates favorable cost and utility outcomes associated with DSAEK for treatment
      of corneal endothelial disease. Longer follow-up of DSAEK outcomes will provide
      more accurate information regarding long-term cost-effectiveness of the
      procedure.

PMID- 22967867
TI  - An updated study of the use of bevacizumab in the treatment of patients with
      prethreshold retinopathy of prematurity in taiwan.
AB  - PURPOSE: To investigate the effectiveness and complications associated with the
      use of bevacizumab, an anti-vascular endothelial growth factor agent, in the
      treatment of prethreshold retinopathy of prematurity (ROP). DESIGN: A
      multicenter, retrospective case series. METHODS: Data from patients who had
      received intravitreal bevacizumab (IVB) injections for the treatment of ROP were
      collected from 4 medical centers in Taiwan. The main outcome measures were the
      regression of ROP and the complications that were associated with the IVB
      injections. RESULTS: In total, 162 eyes from 85 patients were included in the
      study. After receiving IVB injections, 143 eyes (88%) exhibited ROP regression.
      Fourteen eyes (9%) required additional laser treatment for ROP regression after
      the absence of a positive response to the IVB injections. Three eyes (2%)
      progressed to stage 4 ROP and required vitrectomies to reattach the retinas. Two
      eyes (1%) received 1 additional IVB injection to decrease persistent plus
      disease. All of the eyes (100%) had attached retinas after the various treatments
      that they received. The major ocular complications that were associated with IVB
      injections included vitreous or preretinal hemorrhage in 2 eyes (1%); cataract in
      1 eye (1%); and exotropia in 1 eye (1%). No notable systemic complications
      related to the IVB injections were observed. CONCLUSIONS: IVB injection seems to
      be an effective and well-tolerated method of treating prethreshold ROP. Laser
      therapy may still be required as a backup treatment for patients who do not
      respond to an IVB injection or for those in whom ROP worsens after an IVB
      injection.

PMID- 22967868
TI  - Short-term topical bevacizumab in the treatment of stable corneal
      neovascularization.
AB  - PURPOSE: To evaluate the safety and efficacy of topical bevacizumab in the
      treatment of corneal neovascularization. DESIGN: Prospective, nonrandomized,
      interventional case series. METHODS: setting: Institutional, multicenter clinical
      trial. study population: Twenty eyes from 20 patients with stable corneal
      neovascularization. intervention procedures: Patients were treated with topical
      1.0% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. main
      outcome measures: Primary outcome measures included: neovascular area, defined as
      the area of the corneal vessels themselves; vessel caliber, defined as the mean
      corneal vessel diameter; and invasion area, defined as the fraction of the total
      cornea into which the vessels extended. The occurrence of ocular and systemic
      adverse events was monitored closely. RESULTS: As compared with the baseline
      visit, patients exhibited a statistically significant improvement in neovascular
      area by week 6 (P = .007) and in vessel caliber by week 12 (P = .006). At the
      final visit, neovascular area, vessel caliber, and invasion area were reduced by
      47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel
      caliber were statistically significant (P < .001 and P = .003, respectively);
      however, the reduction in invasion area did not reach statistical significance (P
      = .06). There were no significant changes in the secondary outcomes, and there
      were no adverse events. CONCLUSIONS: Short-term topical bevacizumab treatment
      reduced the extent of stable corneal neovascularization as measured by
      neovascular area and vessel caliber with no associated adverse events.
      Interestingly, the degree of treatment efficacy was inversely proportional to the
      baseline invasion area.

PMID- 22967870
TI  - Treatment of infantile capillary hemangioma of the eyelid with systemic
      propranolol.
AB  - PURPOSE: To assess the efficacy and safety of systemic propranolol for infantile
      capillary hemangiomas of the eyelid. DESIGN: Prospective, interventional cases
      series. METHODS: All patients with eyelid infantile capillary hemangiomas at risk
      of developing amblyopia seen between January 2009 and January 2012 at the
      University Federico II, Naples, Italy, were treated with systemic propranolol (2
      mg/kg body weight per day). Maximum length of treatment was 4 months, and
      propranolol was suspended when complete regression of lesions was obtained or in
      case of collateral effects. Minimum follow-up was 6 months. RESULTS: Of 17
      patients with eyelid infantile capillary hemangiomas, 3 were excluded for asthma
      and 14 (7 males, 7 females; mean age, 20.85 +/- 29.7 months; range, 1 to 72
      months) underwent treatment with systemic propranolol. Capillary hemangiomas
      involved the upper eyelid in 10 cases and the lower eyelid in 4 cases.
      Propranolol was stopped in 1 case for hypotension and in 1 case for allergy.
      Treatment was administered over a mean of 2.5 +/- 1.3 months (range, 1 to 4
      months); the mean follow-up was 10.64 +/- 8.7 months (range, 6 to 39 months). Ten
      patients were younger than 1 year and demonstrated complete regression. Two
      patients older than 5 years also benefited from treatment. In 4 cases,
      amblyogenic astigmatism was present and decreased from 1.25 +/- 0.5 diopters
      before treatment to 0.25 +/- 0.2 diopters after treatment. No regrowth was
      observed. CONCLUSIONS: Four months of treatment with oral propranolol for eyelid
      infantile capillary hemangiomas led to complete regression of the lesion in
      patients younger than 1 year. No major collateral effects were observed.
      Treatment also may be considered in patients older than 5 years to reduce
      astigmatism and for aesthetic purposes.

PMID- 22967869
TI  - Initiation of anti-TNF therapy and the risk of optic neuritis: from the safety
      assessment of biologic ThERapy (SABER) Study.
AB  - PURPOSE: To evaluate the incidence of optic neuritis (ON) in patients using anti
      tumor necrosis factor (TNF) alpha therapy. DESIGN: Retrospective, population
      based cohort study. METHODS: We identified new users of anti-TNF therapy
      (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying
      antirheumatic drugs (DMARDs) during 2000-2007 from the following data sources:
      Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the
      Elderly, Tennessee Medicaid, and National Medicaid/Medicare. Within this cohort,
      we used validated algorithms to identify ON cases occurring after onset of new
      drug exposure. We then calculated and compared ON incidence rates between
      exposure groups. RESULTS: We identified 61 227 eligible inflammatory disease
      patients with either new anti-TNF or new nonbiologic DMARD use. Among this
      cohort, we found 3 ON cases among anti-TNF new users, occurring a median of 123
      days (range, 37-221 days) after anti-TNF start. The crude incidence rate of ON
      across all disease indications among anti-TNF new users was 10.4 (95% CI 3.3
      32.2) cases per 100 000 person-years. In a sensitivity analysis considering
      current or past anti-TNF or DMARD use, we identified a total of 6 ON cases: 3
      among anti-TNF users and 3 among DMARD users. Crude ON rates were similar among
      anti-TNF and DMARD groups: 4.5 (95% CI 1.4-13.8) and 5.4 (95% CI 1.7-16.6) per
      100 000 person-years, respectively. CONCLUSION: Optic neuritis is rare among
      those who initiate anti-TNF therapy and occurs with similar frequency among those
      with nonbiologic DMARD exposure.

PMID- 22967871
TI  - World marrow donor association crisis response, business continuity, and disaster
      recovery guidelines.
AB  - Multiple institutions, such as donor registries, donor centers, transplantation
      centers, collection centers, and courier companies, are involved in the
      international exchange of hematopoietic stem cells. The ability to safely and
      efficiently ensure continued operation of a donor registry relies on an
      organization's resiliency in the face of an incident that could impede donor
      search, donor selection, stem cell collection, or transportation. The Quality
      Assurance Working Group of the World Marrow Donor Association has developed
      guidelines on how to establish an organizational resiliency program intended for
      donor registries initiating an emergency preparedness process. These guidelines
      cover the minimal requirements of preparedness in prevention and mitigation,
      crisis response, business continuity, and disaster recovery, and the need for
      continued maintenance and revision. Issues of international cooperation are
      addressed as well.

PMID- 22967873
TI  - Isolation of microsatellite markers for Pelophylax nigromaculata and a tentative
      application in detecting interspecific introgression.
AB  - Twenty-seven microsatellite markers were obtained from the black-spotted frog,
      Pelophylax nigromaculata,using the FIASCO (Fast Isolation by AFLP of Sequences
      containing repeats) protocol. Genotyping of 60 individuals showed that the number
      of alleles ranged from 4 to 25 with an average of 12.78 alleles per locus. The
      observed and expected heterozygosities ranged from 0.137 to 0.956 and 0.594 to
      0.948, with averages of 0.531 and 0.809, respectively. Many of these loci were
      successfully cross-amplified in five other ranid species. The introgression
      between P. nigromaculata and Pelophylax plancyi was assessed using 5
      microsatellite loci on 159 individuals collected from Liaoning, northeast China.
      Two distinct genetic clusters (pure species) as well as seven unassigned
      individuals were identified by factorial correspondence analysis (FCA), New
      Hybrids and Structure. The unassigned individuals, which are likely the product
      of interspecific hybridization, indicate the usefulness of these microsatellite
      loci for future studies of hybridization and introgression between these two
      ranid species.

PMID- 22967872
TI  - Genomic profiling using array comparative genomic hybridization define distinct
      subtypes of diffuse large B-cell lymphoma: a review of the literature.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin
      Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL
      represents a diverse set of lymphomas, defined as diffuse proliferation of large
      B lymphoid cells. Numerous cytogenetic studies including karyotypes and
      fluorescent in situ hybridization (FISH), as well as morphological, biological,
      clinical, microarray and sequencing technologies have attempted to categorize
      DLBCL into morphological variants, molecular and immunophenotypic subgroups, as
      well as distinct disease entities. Despite such efforts, most lymphoma remains
      undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The
      advent of microarray-based studies (chromosome, RNA, gene expression, etc) has
      provided a plethora of high-resolution data that could potentially facilitate the
      finer classification of DLBCL. This review covers the microarray data currently
      published for DLBCL. We will focus on these types of data; 1) array based CGH; 2)
      classical CGH; and 3) gene expression profiling studies. The aims of this review
      were three-fold: (1) to catalog chromosome loci that are present in at least 20%
      or more of distinct DLBCL subtypes; a detailed list of gains and losses for
      different subtypes was generated in a table form to illustrate specific
      chromosome loci affected in selected subtypes; (2) to determine common and
      distinct copy number alterations among the different subtypes and based on this
      information, characteristic and similar chromosome loci for the different
      subtypes were depicted in two separate chromosome ideograms; and, (3) to list re
      classified subtypes and those that remained indistinguishable after review of the
      microarray data. To the best of our knowledge, this is the first effort to
      compile and review available literatures on microarray analysis data and their
      practical utility in classifying DLBCL subtypes.Although conventional cytogenetic
      methods such as Karyotypes and FISH have played a major role in classification
      schemes of lymphomas, better classification models are clearly needed to further
      understanding the biology, disease outcome and therapeutic management of DLBCL.
      In summary, microarray data reviewed here can provide better subtype specific
      classifications models for DLBCL.

PMID- 22967874
TI  - Assessment of changes in DNA methylation by methylation-sensitive amplification
      polymorphism in Jatropha curcas L. subjected to salinity stress.
AB  - The present study assesses the changes in DNA methylation in leaf and root
      tissues of Jatropha curcas L., induced by salinity stress using methylation
      sensitive amplification polymorphism (MSAP) markers. Seedlings of 21 days (d)
      grown under controlled conditions were subjected to 0-100 mM salinity treatment
      for 24 h (1 d). Immediate changes in DNA methylation and polymorphism in
      methylated DNA in whole genome of both leaves and roots were assessed using 10
      selective combinations of MSAP primers. In root and leaves 70.06% and 57.89%
      methylation was observed respectively. Similarly 67.22% and 71.21% polymorphism
      was observed in methylated DNA from root and leaf tissues respectively. Compared
      with control, the percentage of methylation and methylation polymorphism in roots
      of plants under different dosages of salinity was found in the order of 50 mM <
      25 mM = 100 mM < 75 mM and 75 mM < 25 mM < 50 mM < 100 mM respectively. Similarly
      percentage of methylation and methylation polymorphism in leaves of plants
      treated with different levels of salinity was found in order of 75 mM < 25 mM <
      50 mM < 100 mM and 50 mM < 25 mM < 100 mM < 75 mM respectively. The MSAP analysis
      showed that under salt stress homologous nucleotide sequences in genome from
      control and salt treated plants of J. curcas showed different patterns of
      methylation; which suggest that these fragments probably play an important role
      to induce immediate adaptive responses in Jatropha under salinity stress.

PMID- 22967875
TI  - [Not Available].

PMID- 22967876
TI  - Evaluation of two highly sensitive assays for serum IGF-1 and GH determination
      following oral glucose tolerance test in healthy controls.
AB  - OBJECTIVE: To evaluate 2 highly sensitive assays for serum insulin-like growth
      factor-1 (IGF-1) and growth hormone (GH) determination following an oral glucose
      tolerance test (OGTT) in healthy controls. METHODS: Nineteen healthy adults
      underwent a standard 75g OGTT and GH and IGF-1 were measured. Serum GH and IGF-1
      levels were assayed by a sensitive immunoradiometric assay (IRMA) and a highly
      sensitive chemiluminescent immunometric assay (CLIA). RESULTS: The mean IGF-1
      concentration was 153+/-65ng/ml measured by IRMA and 144+/-56ng/ml measured by
      CLIA. The median (interquartile range) basal GH concentrations by IRMAvs CLIA
      were 0.8 (0.5-3) MUg/l vs 0.5 (0.1-2.4) MUg/l. The median nadir GH measured by
      IRMA in these subjects was 0.4 (0.3-0.5) MUg/l, and the mean nadir GH by CLIA was
      0.08 (0.01-0.22) MUg/I. When a ratio of basal IRMA/CLIA GH was calculated in each
      subject, the median ratio of basal IRMA/CLIA GH concentrations in subjects
      overall was 1.68. Similarly, the median ratio of nadir IRMA/CLIA GH values was
      4.44. One of the subjects did not achieve GH suppression into the established
      normal range, with a GH nadir of 1.2 MUg/l by IRMA and 1 MUg/l by CLIA,
      overlapping with the traditional cut-off defining acromegaly when GH suppression
      was measured by IRMA. CONCLUSIONS: Highly sensitive chemiluminescent immunometric
      assays should be used to assess the GH/IGF-1 axis. In our opinion, there is no
      need for a lower GH suppression cut-off for diagnosing acromegaly. We found no
      significant gender-, BMI- or age-related differences in nadir GH levels and thus
      our results do not support different OGTT criteria for screening of acromegaly in
      men and women, or in younger and older subjects.

PMID- 22967877
TI  - Utility of a low-iodide diet in (131)I whole body scanning of patients with
      differentiated thyroid cancer.
AB  - INTRODUCTION: (131)I whole body scanning (WBS) is useful in the follow-up of
      patients with differentiated thyroid carcinoma (DTC). The need to follow a low
      iodide diet (LID) to optimize WBS is widely recognized but there are few reports
      that justify this practice. The aim of this study was to assess levels of urinary
      iodide in patients who underwent WBS in our service and the possible impact of
      some changes to the diet on these levels. PATIENTS AND METHOD: Between January
      2004 and December 2005, we measured iodide levels in 12-h urine samples by paired
      ion-reversed-phase HPLC with electrochemical detection (sensitivity, 0.1 MUg/dl)
      in 371 patients with DTC referred to our service for ablation or follow-up. The
      patients were divided into 2 groups: patients on hormone withdrawal and strict
      LID (group A) and those on hormone withdrawal and generic LID (group B). Urinary
      iodide excretion below 10 MUg/dl was considered low. Data were analyzed by ANOVA
      and chi(2) tests. RESULTS: The mean+/-standard deviation urinary iodide excretion
      was 4.3+/-3 MUg/dl in group A and 5.8+/-3.2 MUg/dl in group B. The mean urinary
      iodide excretion in A group was significantly lower than that in group B
      (p<0.05). CONCLUSIONS: Following a strict LID significantly decreased urinary
      iodide excretion in patients undergoing WBS.

PMID- 22967878
TI  - Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in
      patients with Graves' hyperthyroidism.
AB  - OBJECTIVE: The relapse rate of Graves' hyperthyroidism after finishing an
      antithyroid cicle is high. The objective of this work was to prospectively
      investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with
      maintenance of a low dose of antithyroid drug (ATD) therapy. PATIENTS AND METHOD:
      From March 1997, all patients with GH consecutively attending the same center who
      remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole:
      2.5-5mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in
      this study. Instead of withdrawing ATD, the aim was to continue with this low
      dose for a 5-year period (group M: 53 patients). From March 1997, data were also
      collected from patients with GH who were consecutively followed-up and who,
      meeting the criteria for inclusion in group M, had stopped receiving ATD before
      the start of the study (March 1997) (group R: 31 patients). MAIN OUTCOME: GH
      relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients
      in group R (77.42%) (p<0.000). CONCLUSIONS: The GH relapse rate was significantly
      lower with long-term maintenance of a low dose of ATD than with therapy
      withdrawal.

PMID- 22967879
TI  - Genetic bases of benign thyroid processes.
AB  - The advances made in the last decade in gene analysis techniques have greatly
      simplified the study of the genetic bases of disease, hastening identification of
      the genes causing or involved in disease development. Rapid and low-cost genome
      sequencing in all individuals may become a reality. The genetic bases of defects
      in thyroid hormone formation have been well defined, and those of defects in
      thyroid ontogeny have been partially defined; in the last 4 years, the genes
      responsible for 2 new syndromes causing reduced sensitivity of the action of
      thyroid hormone and affecting thyroid hormone transport (MCT8 mutations) and
      intracellular metabolism (SECISBP2 mutations) have been discovered. The genetic
      bases of toxic adenomas and toxic multinodular goiters have been determined and
      several genes involved in the development of follicular thyroid adenomas have
      been identified. However, not all the genes involved in thyroid ontogeny have
      been identified and the genetic bases of multinodular hyperplastic goiter, highly
      prevalent in some regions of Spain, as well as those of most autoimmune thyroid
      disorders, are unknown. Major challenges remain in the characterization of the
      genetic bases of benign thyroid processes, which, together with their high
      prevalence and the current and future potential of technology, suggest a
      promising and exciting future in this field of research.

PMID- 22967880
TI  - Giant adrenal myelolipoma: case report and literature review.
AB  - Adrenal myelolipomas are rare benign tumors comprising mature adipose tissue and
      diverse hematopoietic elements. These neoplasms are usually incidental findings,
      although bulky masses can generate abdominal pain as well as other symptoms
      related to compression of adjacent organs. Diagnosis is usually provided by
      ultrasonography or computed tomography. Asymptomatic patients with tumors with a
      maximum diameter of less than 6cm can benefit from periodic surveillance, whereas
      local compression symptoms and size larger than 6cm are indications for surgical
      treatment. We present a case of giant adrenal myelolipoma and provide a review of
      the literature.

PMID- 22967881
TI  - Neonatal diabetes: genetic implications in treatment.
AB  - A 2-month-old newborn was diagnosed with diabetes mellitus presenting with
      ketoacidosis and negative islet antibodies. Genetic study revealed the R201C
      mutation of the KCNJ11 gene. In the last few years, the heterozygous activating
      mutation in KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive potassium
      (K(ATP)) channel has been shown to cause permanent neonatal diabetes. Diabetes
      results from impaired insulin secretion caused by failure of the beta cell-K(ATP)
      channel to close in response to increased intracellular ATP. Recent studies have
      demonstrated the effectiveness of oral sulfonylurea in the treatment of this
      disease. Sulfonylurea closes the K(ATP) channel by an ATP-independent route.
      Treatment with sulfonylurea in permanent neonatal diabetes has not yet been
      approved due to the lack of long-term studies in infants. However, the present
      case illustrates the importance of genetics to identify patients who may benefit
      from treatment.

PMID- 22967882
TI  - (123)I-mibg scintigraphy uptake in a hepatic lesion.
AB  - Pheochromocytoma is a tumor derived from the chromaffin cells of the adrenal
      medulla. When this type of tumor involves the sympathetic ganglia it is called
      paraganglioma. Although infrequent, paraganglioma should be considered in the
      evaluation of hypertension, arrhythmias, and panic disorder. We report the case
      of a woman with bladder pheochromocytoma and a hepatic lesion. MIBG scintigraphy
      showed non-physiological uptake, which was interpreted as a false positive
      result.

PMID- 22967883
TI  - Unilateral adrenal incidentaloma as a presentation of adrenal tuberculosis.
AB  - Adrenal incidentalomas are adrenal masses detected during radiologic examination
      performed for an indication otherthan evaluation of adrenal disease. Diagnosis of
      these masses has increased due to the widespread use of ultrasonography, computed
      tomography (CT) and magnetic resonance imaging. We report the case of a 69-year
      old woman with a left adrenal incidentaloma simulating a non-functioning adenoma
      and right adrenal atrophy. The results of contrast-enhanced CT and subsequent
      histopathological study confirmed the diagnosis of adrenal tuberculosis. Hormonal
      study revealed partial adrenal insufficiency as a result of bilateral involvement
      of the adrenal tuberculosis.

PMID- 22967884
TI  - [Not Available].

PMID- 22967885
TI  - Interactions between photodegradation components.
AB  - BACKGROUND: The interactions of p-cresol photocatalytic degradation components
      were studied by response surface methodology. The study was designed by central
      composite design using the irradiation time, pH, the amount of photocatalyst and
      the p-cresol concentration as variables. The design was performed to obtain
      photodegradation % as actual responses. The actual responses were fitted with
      linear, two factor interactions, cubic and quadratic model to select an
      appropriate model. The selected model was validated by analysis of variance which
      provided evidences such as high F-value (845.09), very low P-value (<.0.0001),
      non-significant lack of fit, the coefficient of R-squared (R2 = 0.999), adjusted
      R-squared (Radj2 = 0.998), predicted R-squared (Rpred2 = 0.994) and the adequate
      precision (95.94). RESULTS: From the validated model demonstrated that the
      component had interaction with irradiation time under 180 min of the time while
      the interaction with pH was above pH 9. Moreover, photocatalyst and p-cresol had
      interaction at minimal amount of photocatalyst (< 0.8 g/L) and 100 mg/L p-cresol.
      CONCLUSION: These variables are interdependent and should be simultaneously
      considered during the photodegradation process, which is one of the advantages of
      the response surface methodology over the traditional laboratory method.

PMID- 22967886
TI  - Development of high-pressure and high-field ESR system using SQUID magnetometer.
AB  - We have developed a high-pressure and high-field electron spin resonance (ESR)
      system using the combination of a commercially available superconducting quantum
      interference device (SQUID) magnetometer and a clamp-type piston cylinder
      pressure cell. The magnetic field range is up to 5 T, and the maximum pressure
      reaches 1.5 GPa. The most characteristic feature of this system is its easy
      handling as compared with other high-pressure ESR systems. Moreover, the
      macroscopic magnetization measurement can be performed simultaneously with the
      microscopic ESR measurement. In addition to these features, the well-established
      pressure calibration method utilizing the change of superconducting transition
      temperature of tin can be applied to this system. By using this system, we
      obtained pressure dependence of the single ion magnetic anisotropy parameter D of
      NiSnCl(6).6H(2)O up to 1.5 GPa precisely, and the magnetization behavior of this
      material under pressure was explained well by its pressure dependence of the D
      value.

PMID- 22967887
TI  - Optical lever for monitoring of the magic angle.
AB  - Setting the magic angle and accurately maintaining it over a full range of
      experimental conditions can be a frustrating experience. We present a simple
      optical device for immediate indication of the stator angle, free of mechanical
      uncertainties present in typical adjustment mechanisms.

PMID- 22967888
TI  - Preparation of RNA samples with narrow line widths for solid state NMR
      investigations.
AB  - Solid state NMR can provide detailed structural and dynamic information on
      biological systems that cannot be studied under solution conditions, and can
      investigate motions which occur with rates that cannot be fully studied by
      solution NMR. This approach has successfully been used to study proteins, but the
      application of multidimensional solid state NMR to RNA has been limited because
      reported line widths have been too broad to execute most multidimensional
      experiments successfully. A reliable method to generate spectra with narrow line
      widths is necessary to apply the full range of solid state NMR spectroscopic
      approaches to RNA. Using the HIV-1 transactivation response (TAR) RNA as a model,
      we present an approach based on precipitation with polyethylene glycol that
      improves the line width of (13)C signals in TAR from >6 ppm to about 1 ppm,
      making solid state 2D NMR studies of selectively enriched RNAs feasible at
      ambient temperature.

PMID- 22967889
TI  - Field dependence of the relaxation of 79Br in KBr and its use as a temperature
      calibrant.
AB  - The longitudinal relaxation time of (79)Br nuclei in KBr is field independent,
      between 4.7 T and 14.1 T. The results suggest that inconsistencies in the
      literature are due to differences in the experimental set-ups. The limitations of
      KBr as temperature calibrant are discussed.

PMID- 22967890
TI  - Low rf power high resolution 1H-13C-14N separated local field spectroscopy in
      lyotropic mesophases.
AB  - Efficiency of the proton detected (encoded) (1)H-(13)C-(14)N local field
      spectroscopy technique at low radiofrequency power is examined when applied to
      concentrated ionic lyotropic mesophases exhibiting heteronuclear and homonuclear
      dipolar couplings in kHz range. We demonstrate that highly resolved heteronuclear
      dipolar spectra can be obtained with limited radiofrequency power corresponding
      to decoupling B(1) field of 20 kHz and with superior spectral resolution and
      sensitivity provided by standard solution state probes. To maintain sufficiently
      large spectral window in indirect dimension, power level alternation scheme for
      homonuclear decoupling was introduced. In anisotropic mesophases of an ionic
      surfactant, pair-wise coupling constants in the three-spin system (1)H-(13)C
      (14)N were accurately determined. Relative signs of heteronuclear dipolar
      couplings to nitrogen were obtained employing frequency selective decoupling.

PMID- 22967891
TI  - Corrections for sinusoidal background and non-orthogonality of signal channels in
      sinusoidal rapid magnetic field scans.
AB  - The rapidly-changing magnetic field of sinusoidal rapid scans creates background
      signals that are dominated by oscillations at the scan frequency. The background
      oscillations can be removed without acquiring off-resonance data. For data
      acquired in quadrature, up-field and down-field scan signals can be separated in
      the frequency domain. For each scan direction, the background oscillation can be
      calculated by fitting to the half cycle that does not contain the EPR signal. The
      extrapolated fit function is then subtracted from the half cycle that contains
      the EPR signal. By zeroing the array for the half cycles that do not contain the
      EPR signal, the signal-to-noise is improved and the data are corrected for non
      orthogonality of the quadrature channels.

PMID- 22967892
TI  - Velocity field measurements in sedimentary rock cores by magnetization prepared
      3D SPRITE.
AB  - A time-efficient MRI method suitable for quantitative mapping of 3-D velocity
      fields in sedimentary rock cores, and granular samples is discussed. The method
      combines the 13-interval Alternating-Pulsed-Gradient Stimulated-Echo (APGSTE)
      scheme and three-dimensional Single Point Ramped Imaging with T(1) Enhancement
      (SPRITE). Collecting a few samples near the q-space origin and employing
      restricted k-space sampling dramatically improves the performance of the imaging
      method. The APGSTE-SPRITE method is illustrated through mapping of 3-D velocity
      field in a macroscopic bead pack and heterogeneous sandstone and limestone core
      plugs. The observed flow patterns are consistent with a general trend for
      permeability to increase with the porosity. Domains of low permeability obstruct
      the flow within the core volume. Water tends to flow along macroscopic zones of
      higher porosity and across zones of lower porosity.

PMID- 22967894
TI  - Dual functions of Arabidopsis sulfiredoxin: acting as a redox-dependent sulfinic
      acid reductase and as a redox-independent nuclease enzyme.
AB  - Based on the fact that the amino acid sequence of sulfiredoxin (Srx), already
      known as a redox-dependent sulfinic acid reductase, showed a high sequence
      homology with that of ParB, a nuclease enzyme, we examined the nucleic acid
      binding and hydrolyzing activity of the recombinant Srx in Arabidopsis (AtSrx).
      We found that AtSrx functions as a nuclease enzyme that can use single-stranded
      and double-stranded DNAs as substrates. The nuclease activity was enhanced by
      divalent cations. Particularly, by point-mutating the active site of sulfinate
      reductase, Cys (72) to Ser (AtSrx-C72S), we demonstrate that the active site of
      the reductase function of AtSrx is not involved in its nuclease function.

PMID- 22967893
TI  - Measuring intermolecular rupture forces with a combined TIRF-optical trap
      microscope and DNA curtains.
AB  - We report a new approach to probing DNA-protein interactions by combining optical
      tweezers with a high-throughput DNA curtains technique. Here we determine the
      forces required to remove the individual lipid-anchored DNA molecules from the
      bilayer. We demonstrate that DNA anchored to the bilayer through a single biotin
      streptavidin linkage withstands ~20pN before being pulled free from the bilayer,
      whereas molecules anchored to the bilayer through multiple attachment points can
      withstand ?65pN; access to this higher force regime is sufficient to probe the
      responses of protein-DNA interactions to force changes. As a proof-of-principle,
      we concurrently visualized DNA-bound fluorescently-tagged RNA polymerase while
      simultaneously stretching the DNA molecules. This work presents a step towards a
      powerful experimental platform that will enable concurrent visualization of DNA
      curtains while applying defined forces through optical tweezers.

PMID- 22967896
TI  - Clarification of the C-terminal proteolytic processing site of human
      Amphiregulin.
AB  - Amphiregulin, like other ErbB ligands, is synthesized as a pro-protein which
      requires cleavage at the cell surface to release the active signaling domain.
      Prior studies using a variety of approaches have not yielded a consensus about
      the precise cleavage site. Here we report the purification and protein sequencing
      of the cell-associated human Amphiregulin stalk which remains following cleavage
      of the signaling domain. These data indicate that human Amphiregulin is cleaved
      at Lysine 187, a site homologous to the cleavage site reported in the mouse
      protein and distinct from the Lysine 184 site previously reported for the human
      protein.

PMID- 22967895
TI  - Structure of the GcpE (IspG)-MEcPP complex from Thermus thermophilus.
AB  - Isoprenoid precursor biosynthesis occurs through the mevalonate or the
      methylerythritol phosphate (MEP) pathway, used i.e., by humans and by many human
      pathogens, respectively. In the MEP pathway, 2-C-methyl-D-erythritol-2,4-cyclo
      diphosphate (MEcPP) is converted to (E)-1-hydroxy-2-methyl-but-2-enyl-4
      diphosphate (HMBPP) by the iron-sulfur cluster enzyme HMBPP synthase (GcpE). The
      presented X-ray structure of the GcpE-MEcPP complex from Thermus thermophilus at
      1.55A resolution provides valuable information about the catalytic mechanism and
      for rational inhibitor design. MEcPP binding inside the TIM-barrel funnel induces
      a 60 degrees  rotation of the [4Fe-4S] cluster containing domain onto the TIM
      barrel entrance. The apical iron of the [4Fe-4S] cluster ligates with the C3
      oxygen atom of MEcPP.

PMID- 22967897
TI  - MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2.
AB  - MicroRNAs have the capacity to coordinately repress multiple target genes and
      interfere with biological functions of the cell, such as proliferation and
      apoptosis. Here we report that miR-136 is downregulated in human glioma, and that
      the miRNA promotes apoptosis of glioma cells induced by chemotherapy. Two anti
      apoptotic genes, AEG-1 and Bcl-2, are identified as targets of miR-136, and
      restoration of AEG-1 or Bcl-2 expression suppresses miR-136-enhanced apoptosis.
      Therefore, miR-136 might play a tumor-suppressive role in human glioma and
      thereby might represent a potential therapeutic strategy.

PMID- 22967898
TI  - Determination of cathepsin V activity and intracellular trafficking by N
      glycosylation.
AB  - Cathepsin V (L2), a lysosomal cysteine protease, is a member of cathepsin family,
      relating to cancer invasion and metastasis. Cathepsin V contains two predicted N
      glycosylation sites, but it has not been reported whether cathepsin V is
      glycosylated or not. In this study, we clarified the role of N-glycosylation of
      cathepsin V for its functions. We demonstrated that cathepsin V is N-glycosylated
      at both Asn(221) and Asn(292) using mass spectrometry and site-directed
      mutagenesis. N-glycosylation of cathepsin V was important for transportation to
      lysosome, secretion, and activity in HT1080 cells. These data demonstrated that
      functions of cathepsin V are controlled by N-glycosylation.

PMID- 22967899
TI  - TPCK inhibits AGC kinases by direct activation loop adduction at phenylalanine
      directed cysteine residues.
AB  - N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) has anti-tumorigenic
      properties, but its direct cellular targets are unknown. Previously, we showed
      TPCK inhibited the PDKl-dependent AGC kinases RSK, Akt and S6K1 without
      inhibiting PKA, ERK1/2, PI3K, and PDK1 itself. Here we show TPCK-inhibition of
      the RSK-related kinases MSK1 and 2, which can be activated independently of PDK1.
      Mass spectrometry analysis of RSK1, Aktl, S6K1 and MSK1 immunopurified from TPCK
      treated cells identified TPCK adducts on cysteines located in conserved
      activation loop Phenylalanine-Cysteine (Phe-Cys) motifs. Mutational analysis of
      the Phe-Cys residues conferred partial TPCK resistance. These studies elucidate a
      primary mechanism by which TPCK inhibits several AGC kinases, inviting
      consideration of TPCK-like compounds in chemotherapy given their potential for
      broad control of cellular growth, proliferation and survival.

PMID- 22967900
TI  - Progranulin compensates for blocked IGF-1 signaling to promote myotube
      hypertrophy in C2C12 myoblasts via the PI3K/Akt/mTOR pathway.
AB  - It is well known that growth hormone (GH)-induced IGF-1 signaling plays a
      dominant role in postnatal muscle growth. Our previous studies have identified a
      growth factor, progranulin (PGRN), that is co-induced with IGF-1 upon GH
      administration. This result prompted us to explore the function of PGRN and its
      association with IGF-1. In the present study, we demonstrated that, similar to
      IGF-1, PGRN can promote C2C12 myotube hypertrophy via the PI(3)K/Akt/mTOR
      pathway. Moreover, PGRN can rescue the muscle atrophy phenotypes in C2C12 myotube
      when IGF-1 signaling is blocked. This result shows that PGRN can substitute for
      IGF-1 signaling in the regulation of muscle growth. Our findings provide new
      insights into IGF-1-modulated complicated networks that regulate muscle growth.

PMID- 22967902
TI  - Friendship Characteristics of Children With ADHD.
AB  - OBJECTIVE: This study explored the friendship characteristics of 8 to 12 year old
      children with and without Attention-Deficit/Hyperactivity Disorder (ADHD).
      Friendship characteristics included number of nominated and corroborated friends,
      duration of friendships, amount of contact with friends, and the proportion of
      friends with learning and behavioral problems. METHOD: The sample comprised 92
      children, 50 with a diagnosis of ADHD and 42 comparison children. RESULT: While
      children with ADHD did not differ from comparison children in the number of
      friends they nominated, parents and teachers of children with ADHD were less
      likely to corroborate that these friendships existed. The friendships of children
      with ADHD were also shorter in duration. While children with ADHD were
      indistinguishable from comparison children with regards to the amount of
      telephone contact with friends, they spent less time with friends outside of
      school than comparison children. Children with ADHD had a higher proportion of
      friends with learning and behavior problems. CONCLUSION: While children with ADHD
      differ from comparison children in the above friendship characteristics, it is
      promising that they still fall within the average range for the number of
      corroborated friendships and they demonstrate adequate stability in their
      friendships.

PMID- 22967903
TI  - Occurrence and distribution of psychoactive compounds and their metabolites in
      the urban water cycle of Berlin (Germany).
AB  - The occurrence and distribution of six psychoactive compounds (primidone,
      phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a
      metabolite of primidone (phenylethylmalonamide) were investigated in wastewater
      treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration
      site, raw and final drinking water, and in groundwater affected by former sewage
      irrigation. Primidone and its metabolite phenylethylmalonamide were found to be
      ubiquitous in environmental water samples in Berlin. Maximum concentrations of
      0.87 and 0.42 MUg/L, respectively, were encountered in WWTP effluents. Both
      compounds are apparently not removed when passaging through the different
      compartments of the water cycle and concentrations are only reduced by dilution.
      Phenobarbital was present at nearly every stage of the Berlin water cycle with
      the exception of raw and final drinking water. The highest concentrations of
      phenobarbital (up to 0.96 MUg/L) were measured in groundwater influenced by
      former sewage irrigation. Oxazepam was only present in WWTP effluents and surface
      waters (up to 0.18 MUg/L), while diazepam was not detected in any matrix. Due to
      their withdrawal from the German market years ago, the pharmaceuticals
      meprobamate and pyrithyldione were only found in sewage farm groundwater (up to
      0.50 and 0.04 MUg/L, respectively) and, in case of meprobamate, also in decade
      old bank filtrate (0.03 MUg/L). Our results indicate a high persistence of some
      of the investigated compounds in the aquatic system. As a consequence, these
      pollutants may potentially reach drinking water resources via bank filtration if
      present in WWTP effluents and/or surface waters in partly closed water cycles
      such as Berlin's.

PMID- 22967904
TI  - Delay influences outcome after lower limb major amputation.
AB  - AIM: To investigate if a relationship exists between hospital waiting time to
      major amputation and outcome. METHOD: All patients undergoing major lower limb
      amputation in England between April 2002 and March 2006 were identified from the
      Hospital Episodes Statistics (HES) data. Amputations related to trauma or
      malignancy were excluded. The length of wait (LOW), from date of admission to
      date of major amputation was calculated. A two-level regression model was used to
      investigate if LOW had a significant effect on recovery time and in-hospital
      mortality. Results were adjusted for age, sex, Charlson score, Social
      Deprivation, mode of intervention (bypass/angioplasty/no intervention) and mode
      of admission (emergency/elective). RESULTS: 14,168 major amputations were
      identified. 12,884 (90.9%) had no intervention prior to amputation on that
      admission. Length of Wait (LOW) significantly prolonged recovery in men
      (Exponential Estimate 1.01 1.01-1.02 p < 0.0001) and women (EE 1.02 1.01-1.02 p <
      0.0001) and increased in-hospital mortality in men (OR 1.02 1.02-1.03 p <
      0.0001). Risk of in-hospital death increased by 2% for each day waited.
      CONCLUSION: Delays in decision making or in getting a patient into the operating
      theatre have a negative effect on patient outcome in terms of overall length of
      stay and mortality after major lower limb amputation.

PMID- 22967905
TI  - 'No-touch' saphenous vein harvesting improves graft performance in patients
      undergoing coronary artery bypass surgery: a journey from bedside to bench.
AB  - The saphenous vein is the most commonly used conduit in patients undergoing
      coronary artery bypass surgery yet its patency is inferior to the internal
      thoracic artery. Vascular damage inflicted to the vein when using conventional
      harvesting techniques affects its structure. Endothelial denudation is associated
      with early vein graft failure while damage of the outermost vessel layers has
      adverse long-term effects on graft performance. While many in vitro and in vivo
      experimental studies aimed at improving vein graft patency have been performed to
      date no significant 'bench to bedside' advances have been made. Among
      experimental strategies employed is the use of pharmacological agents, gene
      targeting and external stents. A 'no-touch' technique, where the saphenous vein
      is removed with minimal trauma and normal architecture preserved, produces a
      superior graft with long term patency comparable to the internal thoracic artery.
      Interestingly, many experimental studies are aimed at repairing or replacing
      those regions of the saphenous vein damaged when harvesting conventionally. 'No
      touch' harvesting is superior in coronary artery bypass patients with long-term
      data published 5years ago. Here we describe a 'bedside to bench' situation where
      the mechanisms underlying the improved performance of 'no touch' saphenous vein
      grafts in patients have been studied in the laboratory.

PMID- 22967906
TI  - Transcriptional biomarkers--high throughput screening, quantitative verification,
      and bioinformatical validation methods.
AB  - Molecular biomarkers found their way into many research fields, especially in
      molecular medicine, medical diagnostics, disease prognosis, risk assessment but
      also in other areas like food safety. Different definitions for the term
      biomarker exist, but on the whole biomarkers are measureable biological molecules
      that are characteristic for a specific physiological status including drug
      intervention, normal or pathological processes. There are various examples for
      molecular biomarkers that are already successfully used in clinical diagnostics,
      especially as prognostic or diagnostic tool for diseases. Molecular biomarkers
      can be identified on different molecular levels, namely the genome, the
      epigenome, the transcriptome, the proteome, the metabolome and the lipidome. With
      special "omic" technologies, nowadays often high throughput technologies, these
      molecular biomarkers can be identified and quantitatively measured. This article
      describes the different molecular levels on which biomarker research is possible
      including some biomarker candidates that have already been identified. Hereby the
      transcriptomic approach will be described in detail including available high
      throughput methods, molecular levels, quantitative verification, and
      biostatistical requirements for transcriptional biomarker identification and
      validation.

PMID- 22967909
TI  - Getting the balance right: qualitative evaluation of a holistic weight management
      intervention to address childhood obesity.
AB  - BACKGROUND: Childhood obesity is linked to a range of health and social problems.
      Solutions include the delivery of appropriate weight management interventions for
      those aged 16 and under. The 'Balance It! Getting the Balance Right' programme
      appears to be effective for those who complete the intervention, but the non
      completion rate remains high. A qualitative evaluation was undertaken to explore
      the views of key stakeholders in the programme and identify possible reasons for
      non-completion. METHODS: Semi-structured interviews were conducted with a
      purposive sample of 16 NHS and local authority staff, and with 20 children (aged
      4-16 years) and their families. A mosaic methodology was used, involving visual
      and verbal techniques employed to enable children of all ages to take an active
      role in expressing their opinions. RESULTS: Key themes included the challenges of
      approaching overweight children; positive outcomes for some families; and issues
      relating to communication and coordination. Participants spoke positively about
      the multi-disciplinary approach of 'Balance It!', but felt it could better meet
      the needs of its target population. CONCLUSIONS: Structured interventions help to
      ensure consistency and coherence in terms of approaches to childhood overweight
      and obesity. Whole family approaches may be most effective in enhancing the user
      experience.

PMID- 22967908
TI  - Quality of routine hospital birth records and the feasibility of their use for
      creating birth cohorts.
AB  - BACKGROUND: Linkage between routinely collected hospital birth and other records
      offers the potential for epidemiological and public health research by developing
      population-level birth cohorts with cradle-to-grave follow-up. Data from births
      in English National Health Service hospitals are collected in the Hospital
      Episode Statistics (HES) database but are of uncertain quality. METHODS: We
      examined the range and completeness of birth information recorded in HES and
      tested an approach for minimizing the effect of hospital-level variations by
      selecting hospitals with high completeness of recording (>= 90%) for key fields.
      We discuss important methodological considerations when using routine healthcare
      data to develop a birth cohort. RESULTS: The proportion of missing data in key
      birth record fields has been decreasing annually, such as gestational age and
      birth weight (from 46.2 and 43.9% in 2005/06 to 18.1 and 16.9% in 2009/10,
      respectively). We compared the important characteristics such as size and access
      to specialist neonatal care between 71 high-coding and 85 low-coding hospitals
      and found no significant differences, suggesting hospitals with high birth record
      completeness may be generalizable and representative of all hospitals.
      CONCLUSIONS: The completeness of recording of hospital birth information varies
      greatly between hospitals in England but is improving. It may be preferable and
      valid to construct cohorts from only hospitals with high completeness of
      recording.

PMID- 22967907
TI  - Mechanisms involved in PGE2-induced transactivation of the epidermal growth
      factor receptor in MH1C1 hepatocarcinoma cells.
AB  - BACKGROUND: It is important to understand the mechanisms by which the cells
      integrate signals from different receptors. Several lines of evidence implicate
      epidermal growth factor (EGF) receptor (EGFR) in the pathophysiology of
      hepatocarcinomas. Data also suggest a role of prostaglandins in some of these
      tumours, through their receptors of the G protein-coupled receptor (GPCR) family.
      In this study we have investigated mechanisms of interaction between signalling
      from prostaglandin receptors and EGFR in hepatocarcinoma cells. METHODS: The rat
      hepatocarcinoma cell line MH1C1 and normal rat hepatocytes in primary culture
      were stimulated with EGF or prostaglandin E2 (PGE2) and in some experiments also
      PGF2alpha. DNA synthesis was determined by incorporation of radiolabelled
      thymidine into DNA, phosphorylation of proteins in signalling pathways was
      assessed by Western blotting, mRNA expression of prostaglandin receptors was
      determined using qRT-PCR, accumulation of inositol phosphates was measured by
      incorporation of radiolabelled inositol, and cAMP was determined by
      radioimmunoassay. RESULTS: In the MH1C1 hepatocarcinoma cells, stimulation with
      PGE2 or PGF2alpha caused phosphorylation of the EGFR, Akt, and ERK, which could
      be blocked by the EGFR tyrosine kinase inhibitor gefitinib. This did not occur in
      primary hepatocytes. qRT-PCR revealed expression of EP1, EP4, and FP receptor
      mRNA in MH1C1 cells. PGE2 stimulated accumulation of inositol phosphates but not
      cAMP in these cells, suggesting signalling via PLCbeta. While pretreatment with
      EP1 and EP4 receptor antagonists did not inhibit the effect of PGE2, pretreatment
      with an FP receptor antagonist blocked the phosphorylation of EGFR, Akt and ERK.
      Further studies suggested that the PGE2-induced signal was mediated via Ca2+
      release and not PKC activation, and that it proceeded through Src and shedding of
      membrane-bound EGFR ligand precursors by proteinases of the ADAM family.
      CONCLUSION: The results indicate that in MH1C1 cells, unlike normal hepatocytes,
      PGE2 activates the MEK/ERK and PI3K/Akt pathways by transactivation of the EGFR,
      thus diversifying the GPCR-mediated signal. The data also suggest that the
      underlying mechanisms in these cells involve FP receptors, PLCbeta, Ca2+, Src,
      and proteinase-mediated release of membrane-associated EGFR ligand(s).

PMID- 22967910
TI  - A nanomaterial-based breath test for short-term follow-up after lung tumor
      resection.
AB  - In this case study, we demonstrate the feasibility of nanomaterial-based sensors
      for identifying the breath-print of early-stage lung cancer (LC) and for short
      term follow-up after LC-resection. Breath samples were collected from a small
      patient cohort prior to and after lung resection. Gas-chromatography/mass
      spectrometry showed that five volatile organic compounds were significantly
      reduced after LC surgery. A nanomaterial-based sensor-array distinguished between
      pre-surgery and post-surgery LC states, as well as between pre-surgery LC and
      benign states. In contrast, the same sensor-array could neither distinguish
      between pre-surgery and post-surgery benign states, nor between LC and benign
      states after surgery. This indicates that the observed pattern is associated with
      the presence of malignant lung tumors. The proof-of-concept presented here has
      initiated a large-scale clinical study for post-surgery follow-up of LC patients.
      FROM THE CLINICAL EDITOR: Monitoring for tumor recurrence remains very
      challenging due to post-surgical and radiation therapy induced changes in target
      organs, which often renders standard radiological identification of recurrent
      malignancies inaccurate. In this paper a novel nanotechnology-based sensor array
      is used for identification of volatile organic compounds in exhaled air that
      enable identification of benign vs. malignant states.

PMID- 22967912
TI  - [Not Available].

PMID- 22967911
TI  - Metabolic stress response implicated in diabetic retinopathy: the role of
      calpain, and the therapeutic impact of calpain inhibitor.
AB  - To describe how a high fat diet (HFD) and hyperglycemia initiate a sequence of
      calpain activation and oxidative stress associated with neuro-degenerative
      changes in diabetic retinopathy (DR), hyperglycemia was induced with
      streptozotocin in mice lacking the gene for calpastatin (CAST KO), and in mice
      lacking the gene for the transcription factor NF-E2 related factor 2 (Nrf2 KO).
      All animals were fed a HFD. Retinal ganglion cell (RGC) density was estimated by
      labeling with fluorogold and immunohistochemistry. A potent calpain inhibitor,
      SNJ-1945, was administered daily until the animals were sacrificed. In vitro,
      oxidative stress-induced RGC loss was evaluated in a high glucose culture medium
      with and without SNJ-1945. Retinal mRNA of calpain-1 and calpain-2 was measured
      by quantitative RT-PCR. Pre-apoptotic substrates of cleaved alpha-fodrin and
      synaptophysin protein were quantified by immunoblot analysis. Axonal damage was
      examined in transverse sections of the optic nerve. A HFD and hyperglycemia
      significantly increased RGC and axonal degeneration 3 weeks into the experiment.
      Levels of cleaved alpha-fodrin were increased. In the CAST KO mice, the
      neurotoxicity was augmented significantly. Gene manipulation of CAST and orally
      administered SNJ-1945 successfully modified calpain levels in the retina and
      prevented RGC death. In vitro, a high-glucose culture of retinal cells without
      antioxidants showed more RGC death than that with antioxidant treatment. The
      expression of synaptophysin was significantly suppressed by SNJ-1945 treatment.
      These results suggest that calpain plays a crucial role in metabolic-induced RGC
      degeneration caused by hyperglycemia and oxidative stress. Antioxidant and
      calpain inhibition offers important opportunities for future neuroprotective
      treatment against RGC death in various metabolic stress-induced diseases
      including DR.

PMID- 22967913
TI  - Thyroid disorders and iodine nutritional status in the first trimester of
      pregnancy.
AB  - BACKGROUND AND OBJECTIVES: Thyroid alterations are frequent during pregnancy and
      can be harmful to the development of the newborn. The objective of this study was
      to assess the prevalence of thyroid disorders as well as iodine nutritional
      status in pregnant women in the first trimester of pregnancy. PATIENTS AND
      METHOD: We performed a descriptive observational survey in a health area of
      Toledo (Spain). Participants consisted of pregnant women in this area and a
      control group of non-pregnant women of similar age. Both groups underwent thyroid
      ultrasonography and urinary iodine concentration test. Thyrotropin, free T4 and
      anti-thyroid peroxidase antibodies (anti-TPO Ab) levels were also measured in
      pregnant women. RESULTS: A total of 199 expectant women and a control group of
      169 non-pregnant women participated. The median urinary iodine concentration was
      135 MUg/l (IR, 240-65) in pregnant women and 150MUg/l (IR, 200-90) in the control
      group. The mean values for TSH and free T4 in pregnant women were 1.95+/-1.62 and
      1.03+/-0.15MUU/ml, respectively. The prevalence of hypothyroidism in expectant
      women was 9.5% (95% CI, 6.0-14.7). Thyroid volume was larger in pregnant women
      (12.2+/-5.6mL) than in controls (10.7+/-4.0mL) (p=0.005). Thyroid nodules were
      found in 38.5% of the women in the control group and in 33.2% of pregnant women
      (p = 0.290). CONCLUSIONS: Iodine status was deficient in our group of pregnant
      women. In agreement with the results of other studies performed in Spain, the
      prevalence of hypothyroidism was high. Thyroid hormones and anti-TPO Ab tests
      should be evaluated in the first prenatal visit. The prevalence of nodules was
      similar in pregnant women in the first trimester of pregnancy and in controls.
      Thyroid ultrasonography should be performed in pregnant women whenever a goiter
      and/or thyroid nodules are detected during clinical examination.

PMID- 22967914
TI  - Pheochromocytoma: diagnostic and therapeutic update.
AB  - Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin
      cells of the sympathetic nervous system. In 80-85% of cases, these tumors are
      located in the adrenal medulla while the remainder is located in extra-adrenal
      chromaffin tissues (paragangliomas). Pheochromocytomas account for 6.5% of
      incidentally discovered adrenal tumors. These tumors may be sporadic or the
      result of several genetic diseases: multiple endocrine neoplasia type 2, von
      Hippel-Lindau syndrome, neurofibromatosis type 1, and familial paraganglioma
      associated with mutations in succinate dehydrogenase subunits. Diagnosis of
      pheochromocytoma should first be established biochemically by measuring plasma
      free metanephrines and urinary fractionated metanephrines. The radiological
      imaging tests of choice are computed tomography (CT) or magnetic resonance
      imaging (MRI). The first-line specific functional imaging test is scintigraphy
      with (123)I-metaiodobenzylguanidine (MIBG); if this test is unavailable,
      scintigraphy with (131)I-MIBG is the second choice. Positron emission tomography
      (PET) with (18)F-F-fluorodopamine (F-DA) is useful in metastatic disease. The
      treatment of choice is laparoscopic surgery after adequate alpha adrenergic
      blockade. Approximately 10% of tumors are malignant. Chemotherapy is used for
      inoperable disease. Prognosis is good except in malignant disease, in which 5
      year survival is less than 50%. The identification of the genes causing
      hereditary pheochromocytoma has led to changes in the recommendation for genetic
      testing.

PMID- 22967915
TI  - Zucker rats as an experimental model for the study of various diseases.
AB  - Zucker fatty rats are the best known animal model of genetic obesity. Obesity in
      these animals is inherited as an autosomal recessive trait. Affected rats have a
      mutation in the leptin receptor and show hyperphagia and other alterations
      similar to those that appear in human metabolic syndrome. These animals have
      hyperinsulinemia and can also be considered a model of insulin resistance.
      Nevertheless, the usefulness of Zucker fatty rats as a model of type 2 diabetes
      is questionable, since these animals have only mild glucose intolerance. The
      lipid profile in these animals is also altered. These rats show an increase in
      both very low density lipoproteins (VLDL) and high density lipoproteins (HDL) but
      no increase in LDL cholesterol and these animals cannot be used as a model for
      atherogenesis. Zucker obese rats are not a model for hypertension either, even
      though they show high systolic blood pressure values after 28 weeks of life.

PMID- 22967916
TI  - Severe protein-calorie malnutrition after gastric bypass.
AB  - Bariatric surgery achieves lasting weight loss and improves the comorbidities
      associated with morbid obesity. After surgery, patients can develop
      complications, mainly mild nutritional alterations. However, in some patients,
      complications can be serious and lifethreatening. We present the case of a 50
      year-old woman who developed severe protein-calorie malnutrition after bariatric
      surgery, which required surgical reversion. The factors leading to malnutrition
      in this patient and the treatment options are discussed.

PMID- 22967917
TI  - Diabetes and diarrhea in an elderly woman.
AB  - Between 5 and 10% of adults initially diagnosed with type 2 diabetes
      mellitus.(DM) actually have adult-onset autoimmune diabetes. Given the large
      number of patients diagnosed with DM type 2, the entity called latent autoimmune
      diabetes in adults (LADA) by some authors could represent half of all diabetics
      with type 1A diabetes. We report the case of a 75-year-old woman, with a history
      of brittle diabetes and irritable bowel syndrome, who was finally diagnosed with
      autoimmune diabetes and celiac disease.

PMID- 22967918
TI  - Hepatic involvement in a teenager with type 1 diabetes and poor metabolic
      control.
AB  - There are several manifestations of hepaticinvolvement in diabetes but the most
      frequent is non-alcoholic steatohepatitis. Acquired hepatic glycogenosis is
      characterized by intrahepatocyte glycogen accumulation in poorly controlled type
      1 diabetes under treatment with high doses of insulin. We report the case of a
      diabetic teenager with progressive elevation of liver enzymes associated with
      poor metabolic control. After ruling out other causes of hepatic derangement, we
      made a clinical diagnosis of secondary hepatic glycogenosis without performing
      liver biopsy, as all parameters improved after better glycemic control was
      achieved. Secondary hepatic glycogenosis is probably more frequent than
      previously reported. This process is reversible and has a benign clinical course
      that depends on good metabolic control. Diagnosis can be made clinically. Liver
      biopsy should be reserved for patients with no improvement in liver tests after
      good metabolic control has been achieved.

PMID- 22967919
TI  - Dyspnea and stridor due to multinodular goiter in an obese woman.
AB  - Substernal multinodular goiter is a common entity that may cause life threatening
      pressure symptoms. We report the case of a patient with tracheal stenosis due to
      multinodular goiter and discuss various treatment options.

PMID- 22967920
TI  - Antibacterial activity of silver bionanocomposites synthesized by chemical
      reduction route.
AB  - BACKGROUND: The aim of this study is to investigate the functions of polymers
      and size of nanoparticles on the antibacterial activity of silver
      bionanocomposites (Ag BNCs). In this research, silver nanoparticles (Ag NPs) were
      incorporated into biodegradable polymers that are chitosan, gelatin and both
      polymers via chemical reduction method in solvent in order to produce Ag BNCs.
      Silver nitrate and sodium borohydride were employed as a metal precursor and
      reducing agent respectively. On the other hand, chitosan and gelatin were added
      as a polymeric matrix and stabilizer. The antibacterial activity of different
      sizes of silver nanoparticles was investigated against Gram-positive and Gram
      negative bacteria by the disk diffusion method using Mueller-Hinton Agar.
      RESULTS: The properties of Ag BNCs were studied as a function of the polymer
      weight ratio in relation to the use of chitosan and gelatin. The morphology of
      the Ag BNCs films and the distribution of the Ag NPs were also characterized. The
      diameters of the Ag NPs were measured and their size is less than 20 nm. The
      antibacterial trait of silver/chitosan/gelatin bionanocomposites was
      investigated. The silver ions released from the Ag BNCs and their antibacterial
      activities were scrutinized. The antibacterial activities of the Ag BNC films
      were examined against Gram-negative bacteria (E. coli and P. aeruginosa) and Gram
      positive (S. aureus and M. luteus) by diffusion method using Muller-Hinton agar.
      CONCLUSIONS: The antibacterial activity of Ag NPs with size less than 20 nm was
      demonstrated and showed positive results against Gram-negative and Gram-positive
      bacteria. The Ag NPs stabilized well in the polymers matrix.

PMID- 22967921
TI  - Predictors of exaggerated exercise-induced systolic blood pressures in young
      patients after coarctation repair.
AB  - BACKGROUND: In normotensive subjects, an exaggerated blood pressure response to
      exercise is associated with the development of resting hypertension. We sought to
      determine the prevalence of elevated blood pressures during exercise in post
      operative coarctation patients with normal resting blood pressure, and
      investigate associations with exercise-induced hypertension in this population.
      METHODS: A total of 38 patients were enrolled after end-to-end anastomosis repair
      and resting normotension. All patients underwent anthropometric and blood
      pressure measurements, echocardiographic evaluation of function, arterial
      stiffness assessment by pulse wave velocity, and a graded exercise test. An
      abnormal response was defined as a maximum systolic blood pressure greater than
      the 95th percentile of published normal values. Correlation analyses and stepwise
      regression analyses were performed. RESULTS: The mean age was 12.7 years,
      including 79% male patients. The mean resting systolic blood pressure was 111.3
      millimetres of mercury and the mean exercise systolic blood pressure was 178.1
      millimetres of mercury. The prevalence of a systolic blood pressure greater than
      the 95th percentile was 16.7%. In multivariate analysis, the exercise systolic
      blood pressure index was associated with body mass index, age, aortic valve
      annulus, shortening fraction, and pulse wave velocity (R2 equal to 0.79, p equal
      to 0.0009). Estimates of ventricular filling and indexed left ventricular mass
      were elevated. CONCLUSIONS: There is a risk of elevated systolic blood pressure
      during exercise in normotensive patients after coarctation repair. Resting blood
      pressures are useful but not sufficient. Echocardiography demonstrated
      abnormalities suggestive of a chronic cardiac burden despite resting
      normotension. Regular imaging may be necessary to improve long-term outcomes. New
      paradigms for the continued follow-up of these patients are necessary.

PMID- 22967922
TI  - Projections from melanin-concentrating hormone (MCH) neurons to the dorsal raphe
      or the nuclear core of the locus coeruleus in the rat.
AB  - Brainstem aminergic and cholinergic nuclei are essential components of reticular
      activating system which are under the control of hypothalamic sleep/arousal
      centers. In contrast to well-known role of hypocretin (Hcrt) as a potent wake
      promoting substance, only recent reports stated that melanin-concentrating
      hormone (MCH) plays a role in the maintenance of rapid eye movement (REM) sleep.
      As the sequel to our report concerning the MCH/Hcrt projection to the brainstem
      cholinergic nuclei (Hong et al., 2011), in the present study we examined the
      differential projection from MCH/Hcrt neurons in medial and lateral subdivisions
      of the lateral hypothalamus (LH) to the dorsal raphe (DR) or the nuclear core of
      the locus coeruleus (LC) of the rat. Following the injection of Red Retrobeads
      into the LC core (n=6), the proportions of retrogradely labeled (retro-) MCH
      neurons over the total retro-cells were 4.4% +/- 0.5% (medial subdivision) and
      7.4% +/-0 .6% (lateral one), whereas those of retro-Hcrt cells over the total
      retro-cells were 69.4% +/- 3.6% (medial) and 64.4% +/- 5.2% (lateral). Following
      midline-DR injections (n=6), the proportions of retro-MCH neurons over the total
      retro-cells were 14.3% +/- 2.9% (medial) and 12.3% +/- 1.6% (lateral), while
      those of retro-Hcrt cells over the total retro-cells were 46.5% +/- 6.2% (medial)
      and 51.3% +/- 9.5% (lateral). Following lateral wing-DR injections (n=3), the
      proportions of retro-MCH neurons over the total retro-cells were 15.5% +/- 1.2%
      (medial) and 11.9% +/- 3.1% (lateral), while those of retro-Hcrt cells over the
      total retro-cells were 48.5% +/- 2.7% (medial) and 52.8% +/- 2.3% (lateral). The
      statistical analysis showed that MCH neurons projecting to the LC core or DR were
      outnumbered by Hcrt cells (P<0.01) and that retro-MCH cells exhibited lateral
      predominance in LC injection cases (P<0.05). Based on our present as well as
      previous (Hong et al., 2011) observations, we suggested that MCH and Hcrt neurons
      in the LH provide preferential projections to the brainstem cholinergic and
      aminergic nuclei, respectively and that MCH projections to the nuclear core of
      the LC exhibit differential distribution within LH subdivisions.

PMID- 22967923
TI  - Whole-cell MALDI-TOF MS: a new tool to assess the multifaceted activation of
      macrophages.
AB  - Whole-cell MALDI-TOF MS is routinely used to identify bacterial species in
      clinical samples. This technique has also proven to allow identification of
      intact mammalian cells, including macrophages. Here, we wondered whether this
      approach enabled the assessment human macrophages plasticity. The whole-cell
      MALDI-TOF spectra of macrophages stimulated with IFN-gamma and IL-4, two inducers
      of M1 and M2 macrophage polarisation, consisted of peaks ranging from 2 to 12
      kDa. The spectra of unstimulated and stimulated macrophages were clearly
      different. The fingerprints induced by the M1 agonists, IFN-gamma, TNF, LPS and
      LPS+IFN-gamma, and the M2 agonists, IL-4, TGF-beta1 and IL-10, were specific and
      readily identifiable. Thus, whole-cell MALDI-TOF MS was able to characterise M1
      and M2 macrophage subtypes. In addition, the fingerprints induced by
      extracellular (group B Streptococcus, Staphylococcus aureus) or intracellular
      (BCG, Orientia tsutsugamushi, Coxiella burnetii) bacteria were bacterium
      specific. The whole-cell MALDI-TOF MS fingerprints therefore revealed the
      multifaceted activation of human macrophages. This approach opened a new avenue
      of studies to assess the immune response in the clinical setting, by monitoring
      the various activation patterns of immune cells in pathological conditions.

PMID- 22967924
TI  - Lymphocyte proliferation specific for recall, CMV and HIV antigens in
      miniaturized and automated format.
AB  - Lymphoproliferation assay (LPA) is used to test specific T-cell responses. LPA is
      performed in 96-well plates with 2-5*105 PBMC/well. In order to test numerous
      antigens, as in the case of epitope mapping or screening of antigenic panels from
      relevant pathogens, PBMC numbers may not be sufficient. We developed a
      miniaturized and automated procedure to perform LPA in 384- and 1536-well plates
      with one fourth to one twentieth of PBMC numbers used for standard assays. Here,
      we demonstrate that the procedure is reliable and robust using recall antigens
      and protein and peptide antigens from CMV and HIV. By using HIV specific T-cell
      lines, we also demonstrate that sensitivity ranges overlap with those of standard
      LPA and that as few as 3 specific cells/well provide a positive signal. This
      procedure is consistent with our policy to miniaturize assays for specific T-cell
      immunity, as we have already established for cytokine secretion assays.

PMID- 22967925
TI  - Impact of maternally-derived antibodies against Salmonella enterica serovar
      Typhimurium on the bacterial load in suckling piglets.
AB  - The significance of maternal immunity against non-typhoid Salmonella spp.
      acquired by piglets via colostrum and milk was evaluated in a Salmonella enterica
      serovar Typhimurium challenge experiment. Piglets from sows vaccinated with an
      experimental inactivated vaccine exhibited high levels of serum immunoglobulins G
      and A against S. Typhimurium 4 days after birth, just prior to experimental oral
      challenge. The S. Typhimurium load in the ileal and caecal wall of piglets 3 days
      after experimental inoculation was lower by a 2-log magnitude compared to
      unvaccinated controls. Such a vaccine, delivering colostral/lactogenic immunity
      to piglets thus has the potential to reduce the prevalence non-typhoid Salmonella
      spp. infection.

PMID- 22967926
TI  - Antimicrobial resistance changes in enteric Escherichia coli of horses during
      hospitalisation: resistance profiling of isolates.
AB  - The aim of this study was to determine whether hospitalisation of horses leads to
      increased antimicrobial resistance in equine faecal Escherichia coli isolates. E.
      coli were cultured from faecal samples of horses on admission and after 7 days of
      hospitalisation; antimicrobial susceptibility was determined for eight
      antimicrobial agents. Resistance profiles of E. coli isolates were grouped into
      clusters, which were analysed to determine resistance patterns. Resistance to 7/8
      antimicrobial agents and multi-drug resistance (MDR; resistance to >=3
      antimicrobial classes) were significantly higher after 7 days of hospitalisation.
      Forty-eight resistance profiles were identified; 15/48 were present on day 0
      only, 16/48 on day 7 only and 17/48 at both times of sampling. There was a
      significant association between day 7 profiles and resistance detected to an
      increased number of antimicrobial agents. Hospitalisation of horses for 7 days
      resulted in alterations in equine faecal E. coli antimicrobial resistance
      profiles.

PMID- 22967927
TI  - The prevalence and clinical relevance of hyperkalaemia in calves with neonatal
      diarrhoea.
AB  - One hundred and twenty-four calves with neonatal diarrhoea were investigated in
      order to assess the prevalence of hyperkalaemia and the associated clinical
      signs. Hyperkalaemia (potassium concentration >5.8mmol/L) was recognized in 42
      (34%) calves and was more closely associated with dehydration than with decreases
      in base excess or venous blood pH. In 75 calves with normal blood concentrations
      of D-lactate (i.e. ?3.96mmol/L), K concentrations were moderately correlated with
      base excess values (r=-0.48, P<0.001). In contrast, no significant correlation
      was observed in 49 calves with elevated D-lactate. Only three hyperkalaemic
      calves had bradycardia and a weak positive correlation was found between heart
      rate and K concentrations (r=0.22, P=0.014). Ten of the 124 calves had cardiac
      arrhythmia and of these seven had hyperkalaemia indicating that cardiac
      arrhythmia had a low sensitivity (17%) but a high specificity (96%) as a
      predictor of hyperkalaemia. In a subset of 34 calves with base excess values ?
      5mmol/L and D-lactate concentrations <5mmol/L (of which 22 had hyperkalaemia),
      changes in posture/ability to stand could be mainly explained by elevations of K
      concentrations (P<0.001) and to a lesser extent by increases in L-lactate
      concentrations (P=0.024). Skeletal muscle weakness due to hyperkalaemia alongside
      hypovolaemia may produce a clinical picture that is similar to that in calves
      with marked D-lactic acidosis. However, since reductions in the strength of the
      palpebral reflex are closely correlated with D-lactate concentrations, a prompt
      palpebral reflex can assist the clinical prediction of hyperkalaemia in calves
      presenting with a distinct impairment in their ability to stand (specificity 99%,
      sensitivity 29%).

PMID- 22967928
TI  - The effect of environmentally relevant conditions on PVP stabilised gold
      nanoparticles.
AB  - Nanoparticles are a major product from the nanotechnology industry and have been
      shown to have a potentially large environmental exposure and hazard. In this
      study, sterically stabilised polyvinyl pyrrolidone (PVP) 7 nm gold nanoparticles
      (NPs) were produced and characterised as prepared by surface plasmon resonance
      (SPR), size and aggregation, morphology and surface charge. Changes in these
      properties with changes in environmentally relevant conditions (pH, ionic
      strength, Ca concentration and fulvic acid presence) were quantified. These
      sterically stabilised NPs showed no aggregation with changes in pH or inorganic
      ions, even under high (0.1 M) Ca concentrations. In addition, the presence of
      fulvic acid resulted in no observable changes in SPR, size, aggregation or
      surface chemistry, suggesting limited interaction between the PVP stabilised
      nanoparticles and fulvic acid. Due to the lack of aggregation and interaction,
      these NPs are expected to be highly mobile and potentially bioavailable in the
      environment.

PMID- 22967929
TI  - Chemometric interpretation of vertical profiles of radionuclides in soils near a
      Spanish coal-fired power plant.
AB  - The study of the vertical distribution of seven radionuclides in soils around a
      coal fired power plant in a mountain region in the north of Spain has been
      performed, in order to know if some deposition and migration of these
      radionuclides has taken place. Thirteen profiles of 30 cm depth have been
      selected, and every fraction of 5 cm has been analyzed until of a total of 72
      soil samples. The activity concentration of (238)U, (226)Ra, (210)Pb, (232)Th,
      (224)Ra, (40)K and (137)Cs has been measured by gamma-ray spectrometry. The data
      were analyzed using multivariate statistical techniques, founding the best result
      when using a simple two-factor model, which can explain the 81.1% of the total
      variance. Additionally, on the basis of the significant differences found in the
      concentration of lead in the soil top and deep layers, the evaluation of excess
      of (210)Pb and the K-parameter was done. A good correlation between the excess of
      (210)Pb and the concentration of anthropogenic radionuclide (137)Cs in surface
      soil was found. These results confirm the atmospheric deposition of lead as a
      decay product of exhaled Rn.

PMID- 22967931
TI  - The primary biodegradation of dispersed crude oil in the sea.
AB  - Dispersants are important tools for stimulating the biodegradation of large oil
      spills. They are essentially a bioremediation tool - aiming to stimulate the
      natural process of aerobic oil biodegradation by dispersing oil into micron-sized
      droplets that become so dilute in the water column that the natural levels of
      biologically available nitrogen, phosphorus and oxygen are sufficient for
      microbial growth. Many studies demonstrate the efficacy of dispersants in getting
      oil off the water surface. Here we show that biodegradation of dispersed oil is
      prompt and extensive when oil is present at the ppm levels expected from a
      successful application of dispersants - more than 80% of the hydrocarbons of
      lightly weathered Alaska North Slope crude oil were degraded in 60 d at 8 
      degrees C in unamended New Jersey (USA) seawater when the oil was present at 2.5
      ppm by volume. The apparent halftime of the biodegradation of the hydrocarbons
      was 13.8 d in the absence of dispersant, and 11 d in the presence of Corexit 9500
      - similar to rates extrapolated from the field in the Deepwater Horizon response.

PMID- 22967930
TI  - Bioaccumulation and uptake routes of perfluoroalkyl acids in Daphnia magna.
AB  - Perfluoroalkyl acids (PFAs), one kind of emerging contaminants, have attracted
      great attentions in recent years. However, the study about their bioaccumulation
      mechanism remains scarce. In this research, the bioaccumulation of six kinds of
      PFAs in water flea Daphnia magna was studied. The uptake rates of PFAs in D.
      magna ranged from 178 to 1338 L kg(-1) d(-1), and they increased with increasing
      perfluoroalkyl chain length; the elimination rates ranged from 0.98 to 2.82 d(
      1). The bioaccumulation factors (BAFs) of PFAs ranged from 91 to 380 L kg(-1) in
      wet weight after 25 d exposure; they increased with increasing perfluoroalkyl
      chain length and had a significant positive correlation with the n-octanol/water
      partition coefficients (logK(ow)) of PFAs (p<0.05). This indicated that the
      hydrophobicity of PFAs plays an important role in their bioaccumulation. The BAFs
      almost kept constant when the PFA concentrations in aqueous phase increased from
      1 to 10 MUg L(-1). Scenedesmus subspicatus, as the food of D. magna, did not
      significantly affect the bioaccumulation of PFAs by D. magna. Furthermore, the
      body burden of PFAs in the dead D. magna was 1.08-2.52 times higher than that in
      the living ones, inferring that the body surface sorption is a main uptake route
      of PFAs in D. magna. This study suggested that the bioaccumulation of PFAs in D.
      magna is mainly controlled by their partition between organisms and water;
      further research should be conducted to study the intrinsic mechanisms,
      especially the roles of protein and lipid in organisms.

PMID- 22967932
TI  - Opening/blocking actions of pyruvate kinase antibodies on neuronal and muscular
      KATP channels.
AB  - ATP-sensitive-K(+) (KATP) channels couple metabolism to the electrical activity
      of the cells. This channel is associated with glycolytic enzymes to form
      complexes regulating the channel activity in various tissues. The pyruvate-kinase
      (PK) enzyme is an antigen in the Paediatric Autoimmune Neuropsychiatric Disorders
      Associated Streptococcal infection known as PANDAS which is characterized by an
      abnormal production of auto-antibodies against PK. Here, the effects of the anti
      pyruvate kinase antibody (anti-PK-ab) on the muscle and neuronal KATP channels
      were investigated in native rat skeletal muscle fibres and human neuroblastoma
      cell-line (SH-SY5Y), respectively. Furthermore, the interaction of PK with the
      inwardly rectifier potassium channel (Kir6.1/Kir6.2) subunits of the KATP
      channels was investigated by co-immunoprecipitation experiments in mouse brain
      using the anti-PK-ab. Patch-clamp experiments showed that the short-term
      incubation (1h) of the fibres with the anti-PK-ab at the dilutions of 1:500 and
      1:300 enhanced the KATP current of 19.6% and 33.5%, respectively. As opposite,
      the long-term incubation (24h) of the fibres with the anti-PK-ab at the dilutions
      of 1:500 and 1:300 reduced the KATP current of 16% and 24%, respectively,
      reducing the diameter with atrophy. The direct application of the anti-PK-ab to
      the excised patches in the absence of intracellular ATP caused channel block,
      while in the presence of nucleotide channel opened. In neuronal cell line, in the
      short-term the anti-PK-ab potentiated KATP currents without affecting survival,
      while in the long-term the anti-PK-ab reduced KATP currents inducing neuronal
      death. Opening/blocking actions of the anti-PK antibodies on the KATP channels
      were observed, the blocking action causes fibre atrophy and neuronal death. We
      demonstrated that PK and Kir subunits are physically/functionally coupled in
      neurons. The KATP/PK complex can be proposed a novel target in the autoimmune
      diseases associated with anti-PK production as in PANDAS.

PMID- 22967933
TI  - The relationship between body weight, frailty, and the disablement process.
AB  - OBJECTIVES: To prospectively examine the relationship between body weight,
      frailty, and the disablement process. METHOD: Longitudinal data from the Health
      and Retirement Study (1998-2006) were used to examine the relationship between
      being underweight, overweight, or obese (compared with normal weight) and the
      onset and progression of functional limitations and disabilities in instrumental
      activities of daily living (IADL) and activities of daily living (ADL) among a
      nationally representative sample of community-dwelling older adults (aged 50 and
      older) with characteristics of frailty (n= 11,491). Nonlinear multilevel models
      additionally adjusted for demographic characteristics and intra-individual
      changes in body weight, socioeconomic status, health behaviors, and health
      conditions over the course of 8 years. RESULTS: Compared with their nonfrail
      normal weight counterparts, prefrail obese respondents have a 16% (p <= 0.001)
      reduction in the expected functional limitations rate and frail overweight and
      obese respondents have a 10% (p <= 0.01) and 36% (p <= 0.001) reduction in the
      expected functional limitations rate, respectively. In addition, frail obese
      respondents have a 27% (p <= 0.05) reduction in the expected ADL disability rate.
      DISCUSSION: This study's findings suggest that underweight, overweight, and obese
      status differentially affect the risk for functional limitations and disabilities
      in IADL and ADL. Among prefrail and frail adults, some excess body weight in
      later life may be beneficial, reducing the rate of functional limitations and
      disability.

PMID- 22967939
TI  - Supporting a psychiatric hospital culture of safety.
AB  - BACKGROUND: Concerns for patient safety have risen to the forefront of health
      care, including mental health care. Safe patient care depends, to a large extent,
      on high functioning teams, yet team training is lacking in basic professional
      training programs. To address the need for team training, one psychiatric
      hospital adopted the Team Strategies and Tools to Enhance Performance and Patient
      Safety program (TeamSTEPPS). OBJECTIVES: To describe the implementation of
      TeamSTEPPS throughout the organization and to describe the differences in team
      attributes prior to and following implementation of TeamSTEPPS. DESIGN: Quality
      improvement project using a pre-post survey design. RESULTS: TeamSTEPPS was
      successfully implemented, and changes in all team attributes trended in a
      positive direction with 5 of 7 subscales reaching significance (p <= .01).
      CONCLUSIONS: TeamSTEPPS provided a practical approach for our hospital to
      systematically weave safety throughout the culture and improve team functioning
      and other attributes of highly effective teams.

PMID- 22967940
TI  - Quantitative analysis of spin exchange interactions to identify beta strand and
      turn regions in Ure2 prion domain fibrils with site-directed spin labeling.
AB  - Amyloid formation is associated with a range of debilitating human disorders
      including Alzheimer's and prion diseases. The amyloid structure is essential for
      understanding the role of amyloids in these diseases. Amyloid formation of Ure2
      protein underlies the yeast prion [URE3]. Here we use site-directed spin labeling
      and electron paramagnetic resonance (EPR) spectroscopy to investigate the
      structure of amyloid fibrils formed by the Ure2 prion domain. The Ure2 prion
      domain under study contains a Sup35M domain at C-terminus as a solubilization
      element. We introduced spin labels at every residue from positions 2-15, and
      every 5th residue from positions 20-80 in Ure2 prion domain. EPR spectra at most
      labeling sites show strong spin exchange interactions, suggesting a parallel in
      register beta structure. With quantitative analysis of spin exchange
      interactions, we show that residues 8-12 form the first beta strand, followed by
      a turn at residues 13-14, and then the second beta strand from residue 15 to at
      least residue 20. Comparison of the spin exchange frequency for the fibrils
      formed under quiescent and agitated conditions also revealed differences in the
      fibril structures. Currently there is a lack of techniques for in-depth
      structural studies of amyloid fibrils. Detailed structural information is
      obtained almost exclusively from solid-state NMR. The identification of beta
      strand and turn regions in this work suggests that quantitative analysis of spin
      exchange interactions in spin-labeled amyloid fibrils is a powerful approach for
      identifying the beta-strand and turn/loop residues and for studying structural
      differences of different fibril polymorphs.

PMID- 22967942
TI  - Dissolution patterns of biocompatible glasses in 2-amino-2-hydroxymethyl-propane
      1,3-diol (Tris) buffer.
AB  - A continuous flow measurement system with sensitive on-line ion analysis has been
      applied to study the initial dissolution behaviour of biocompatible glasses in
      Tris. Altogether 16 glasses with widely varying compositions were studied. The
      measurement system allowed for quantitative determination of the time-dependent
      rates of dissolution of sodium, potassium, calcium, magnesium, silicon and
      phosphorus during the first 10-15 min in contact with Tris solution. The
      dissolution rates of the different ions showed significant glass to glass
      variations, but all glasses studied showed one of four distinct dissolution
      patterns. The ion dissolution rates after an exposure of 1000 s, expressed as the
      normalized surface-specific mass loss rates, were compared with the in vitro and
      in vivo reactivity of the glasses as predicted by models in the literature. The
      results showed a clear correlation between the dissolution rates of the glasses
      in Tris and their reactivity as measured by other different methods.
      Consequently, the measured short-term dissolution patterns could be used to
      determine which glasses are suitable as bioactive, biodegradable, or inert
      biomaterials for medical devices.

PMID- 22967941
TI  - Knockdown of clusterin sensitizes pancreatic cancer cells to gemcitabine
      chemotherapy by ERK1/2 inactivation.
AB  - OBJECTIVES: To study the hypothesis that gemcitabine treatment augments the
      chemoresistance to gemcitabine by clusterin (sCLU) upregulation. Clusterin
      inhibition could augment the chemosensitivity of human pancreatic cancer cells by
      inhibition of clusterin-dependent pERK1/2 activation. METHODS: Clusterin was
      silenced by serial concentration of OGX-011 transfection in pancreatic cancer
      MIAPaCa-2 and BxPC-3 cell lines, then treated with serial concentration of
      gemcitabine. After the cells were treated with OGX-011 for 8 h, the cells were
      then treated with 5 MUM ERK inhibitor PD98059 for 18 h or transfected with a wt
      pERK-expressing plasmid into these cells for 24 h, after which the cells were
      treated with 1.0 uM gemcitabine for 24-72 h. Cell proliferation was determined by
      MTT. Apoptosis was quantified by flow cytometry,.sCLU and pERK1/2 production was
      analyzed by western blot, and sCLU mRNA was analyzed by RT-PCR. Xenograft of
      established tumors was used to evaluate primary tumor growth and apoptosis after
      treatment with gemcitabine alone or in combination with OGX-011. Phosphorylated
      ERK1/2 and sCLU levels in tumor tissues were measured by TUNEL analysis. RESULTS:
      As detected by MTT and FACS assay, a combination of gemcitabine + OGX-011
      reflected the chemotherapeutic sensitivity and increased the gemcitabine -induced
      apoptosis in MIAPaCa-2 and BxPC-3 cells. Western blotting and RT-PCR analysis
      revealed that the expression of clusterin was higher in gemcitabine -resistant
      MIAPaCa-2 cells, however, decreased significantly after pretreatment with OGX
      011. Furthermore, the OGX-011 or combination of gemcitabine + OGX-011 decreased
      the gemcitabine -induced activation of pERK1/2. wt-pERK-re-expression decreased
      OGX-011+ gemcitabine -induced apoptosis. Finally, OGX-011 in combination with
      gemcitabine substantially decreased the in vivo tumor growth and promoted
      apoptosis. Taken together, clusterin confers gmcitabine resistance in pancreatic
      cancer cells. CONCLUSIONS: Knockdown of clusterin by OGX-011 transfection
      sensitizes pancreatic cancer cells to gemcitabine by inhibition of gemcitabine 
      induced clusterin-pERK1/2 activation.

PMID- 22967943
TI  - Enhanced adolescent learning and hippocampal axonal projections following
      preadolescent spatial exposure to a water or dry maze.
AB  - The present work sought to determine whether preadolescent exposure to a
      different task in the same spatial environment would lead to enhancement of water
      maze performance and changes in hippocampal connectivity. Separate groups of
      preadolescent (p16-p26) Long Evans rats (LER) were exposed to the same room and
      arena using either a water-maze (WM) or a dry-maze (DM), while a third group
      received no exposure to the spatial cues (NT) but were handled. Three weeks
      later, rats were tested on the WM or DM task in the same room where preadolescent
      exposure took place. This set up conditions where the DM/WM and WM/DM groups were
      exposed to the same spatial cues during the preadolescent and adolescent (p40
      p44) phases but performed different tests allowing for the dissociation of
      spatial cue exposure and task familiarity on adolescent performance. When animals
      experienced similar preadolescent and adolescent conditions (WM/WM or DM/DM),
      there was improved performance over animals with no preadolescent spatial
      exposure (NT/WM or NT/DM). In group DM/WM, there was enhanced adolescent
      performance compared to group NT/WM. In contrast, group WM/DM did not show
      enhanced adolescent performance. Compared to groups with no preadolescent spatial
      exposure, groups with both preadolescent and adolescent spatial exposure showed
      elevated synaptophysin staining in the hippocampal CA3 region indicating an
      expanded axonal projection in this region. These data suggest the possibility
      that exposure to spatial cues during the preadolescent period, independent from
      task-specific requirements, contributes to enhanced adolescent spatial
      performance on the WM. This appears to be linked with the reorganization of
      axonal inputs to the CA3 region.

PMID- 22967944
TI  - Heritability of ambulatory and beat-to-beat office blood pressure in large
      multigenerational Arab pedigrees: the 'Oman Family study'.
AB  - OBJECTIVE: To estimate the heritability of ambulatory blood pressure (BP), heart
      rate (HR), and beat-to-beat office BP and HR in an isolated, environmentally and
      genetically homogeneous Omani Arab population. METHODS: Ambulatory BP
      measurements were recorded in 1,124 subjects with a mean age of 33.8 +/- 16.2
      years, using the auscultatory mode of the validated Schiller ambulatory BP
      Monitor. Beat-to-beat BP and HR were recorded by the Task Force Monitor.
      Heritability was estimated using quantitative genetic analysis. This was achieved
      by applying the maximum-likelihood-based variance decomposition method
      implemented in SOLAR software. RESULTS: We detected statistically significant
      heritability estimates for office beat-to-beat, 24-hour, daytime, and sleep HR of
      0.31, 0.21, 0.20, and 0.07, respectively. Heritability estimates in the above
      mentioned conditions for systolic BP (SBP)/diastolic BP (DBP)/mean BP (MBP)were
      all significant and estimated at 0.19/0.19/0.19, 0.30/0.44/0.41, 0.28/0.38/0.39,
      and 0.21/0.18/0.20,respectively. Heritability estimates for 24-hour and daytime
      ambulatory SBP, DBP, and MBP ranged from 0.28 to 0.44, and were higher than the
      heritability estimates for beat-to-beat recordings and sleep periods,which were
      estimated within a narrow range of 0.18-0.21. CONCLUSION: In this cohort, because
      shared environments are common to all, the environmental influence that occurs is
      primarily due to the variation in non-shared environment that is unique to the
      individual. We demonstrated significant heritability estimates for both beat-to
      beat office and ambulatory BP and HR recordings, but 24-hour and daytime
      ambulatory heritabilities are higher than those from beat-to-beat resting levels
      and ambulatory night-time recordings.

PMID- 22967947
TI  - A clinical analysis of nine new pediatric and adolescent cases of benign minor
      salivary gland neoplasms and a review of the literature.
AB  - INTRODUCTION: Minor salivary gland neoplasms of epithelial origin are rare in
      children and adolescents and most are not well documented, except for a few small
      series and case reports. This study represents a retrospective clinical analysis
      of nine cases of benign epithelial salivary gland neoplasms accessioned over a 35
      year period at the Louisiana State University School of Dentistry and combines
      the data with well-documented cases from the English-language literature.
      METHODS: A retrospective clinical analysis of nine cases of benign epithelial
      salivary gland neoplasms was performed over a 35-year period at the Louisiana
      State University School of Dentistry and combined with data of well-documented
      cases from the English-language literature. RESULTS: The nine benign salivary
      gland neoplasms in patients aged 19 months to 18 years accounted for 2.3% of the
      Louisiana State University School of Dentistry accessioned salivary gland tumors.
      These nine cases comprised eight pleomorphic adenomas and one cystadenoma. There
      were 40 cases in the literature, of which 34 were pleomorphic adenomas. Combining
      the data for the 42 pleomorphic adenomas resulted in a mean age of 12 years with
      a 2.8:1 female predilection. The hard palate and/or soft palate were the most
      common site (69.1%). The average duration and size was 2.1 years and 2.4cm,
      respectively. Bone involvement occurred in seven cases. Wide local excision was
      the treatment most often employed. Cases followed for two years or more had a
      recurrence rate of 13.0%. The remaining seven neoplasms in the combined data
      comprised myoepithelioma, cystadenoma and sialadenoma papilliferum. CONCLUSIONS:
      A relatively long duration (2 years) of a submucosal mass in a minor salivary
      gland-bearing area with or without bone involvement occurring in a child or
      adolescent should raise the question of a possible salivary gland neoplasm. A
      pleomorphic adenoma is the most common benign salivary gland neoplasm in the
      first and second decade of life. Complete surgical excision affords the best
      chance of preventing recurrence for pleomorphic adenomas. The recurrence rate of
      pleomorphic adenomas with two or more years follow-up is 13.0%. Other types of
      minor salivary gland neoplasms are exceedingly rare and therefore data is sparse,
      precluding any valid conclusions.

PMID- 22967948
TI  - Chimerism analysis in transplant patients: a hypothesis-free approach in the
      absence of reference genotypes.
AB  - INTRODUCTION: During routine analysis of chimerism in bone marrow transplant
      patients pre-transplant genotype of the recipient or the donor might lack. We
      aimed to develop a new method to analyze DNA results suitable when reference
      genotypes are not available. METHODS: The method was based on the balance between
      heterozygotes. It was implemented in a standard computer spreadsheet, and
      considered the hypothetical donor-recipient genotype combinations. Hypotheses
      with peak height ratios and allele sharing tendency above a critical threshold
      were accepted. The results were compared with those obtained with prior knowledge
      of reference genotypes. RESULTS: The algorithm predicted correctly the proportion
      of donor/recipient chimerism, even in the absence of reference genotypes. In
      fact, the predicted values were closely correlated (r(2)>0.98) and free of
      systematic bias (slope 0.98-1.04), in comparison with the reference values
      obtained with prior knowledge of the donor and recipient genetic profiles.
      CONCLUSIONS: This study constitutes a proof-of-concept of the application of the
      heterozygote balance for the quantitative study of chimerism. The algorithm
      computes post-transplant chimerism in an easy and time-efficient way, even when
      the donor and recipient reference genotypes are unavailable. Therefore, it can be
      a useful tool for laboratories involved in chimerism analysis.

PMID- 22967949
TI  - Detection of thromboembolism with 99mTc-labeled F(ab)2 fragment of anti
      glycoprotein IIIa chimeric monoclonal antibody in beagle canines.
AB  - INTRODUCTION: Rapid and timely diagnosis of pulmonary embolism (PE) and deep
      venous thrombosis (DVT) is important to improve patient outcome. The goal of this
      study was using (99m)Tc-chSZ21-F(ab)(2), F(ab)(2) fragment of anti-glycoprotein
      IIIa chimeric monoclonal antibody, to image experimental thromboembolism (DVT and
      PE) in dogs. MATERIALS AND METHODS: Flow cytometry assay and adenosine
      diphosphate (ADP) stimulated platelet aggregation was performed to determine the
      specificity and affinity of chSZ21-F(ab)(2) to the GPIIb/IIIa receptor on human
      or canine platelets. Both PE and DVT were induced in 12 beagle canines by
      catheter under X-ray direction. After (99m)Tc-chSZ21-F(ab)(2) injection,animals
      were imaged for up to 3 hours then heparinized and sacrificed. RESULTS: Specific
      binding of chSZ21-F (ab)(2) to GPIIb/IIIa on human or canine platelets was
      verified by flow cytometry assay. chSZ21-F (ab)(2) inhibited ADP induced platelet
      aggregation with a dose-dependent manner, the concentration required to inhibit
      50% (IC(50)) of platelet aggregation was 11.6 +/- 7.9 nM and 24.9 +/- 18.8 nM for
      human and canine, respectively. In vivo, focal uptake was observed in planar
      images as early as 30 min (DVT) and 60 min (PE), and became clearer within 3
      hours after injection. Lesion-to-background ratio averaged 12.8 (PE-to-lung), 7.2
      (DVT-to-blood), and 117.0(DVT-to-muscle), respectively. CONCLUSIONS: These
      results suggested that (99m)Tc-chSZ21-F(ab)(2) with high DVT and PE uptake is a
      promising agent for imaging vascular thrombosis.

PMID- 22967950
TI  - The effects of externally applied pressure on the ultrasonic degradation of
      Rhodamine B.
AB  - The present manuscript compares the ultrasonic degradation of Rhodamine B dye
      under atmospheric (1 bar) and elevated pressures (1.6 and 2 bar). The degradation
      was studied as a function of the bulk liquid temperature and initial dye
      concentration at two different values of mechanical amplitudes (ultrasonic
      intensities). Results indicate that at the low amplitude an increase in the
      applied pressure increases the dye removal rate, whereas at the high amplitude,
      the same increase in the pressure has a minimal effect on the degradation of the
      dye. Furthermore, at low amplitudes an increase in the bulk liquid temperature
      from 5 to 35  degrees C increases the dye degradation by 10%. At higher
      intensities, the same increase in temperature has negative or no effect on the
      dye removal. An increase in the initial dye concentration by one order of
      magnitude significantly lowers the dye degradation rate regardless of the applied
      amplitude. Though these results are caused by numerous physical and chemical
      processes taking place during ultrasonic cavitation, the number of cavitation
      sites, bubble temperature and consequently, the amount of oxidative species
      inside the bubble seem to be the most important ones in determining the extent of
      the degradation of molecules in the bulk liquid.

PMID- 22967951
TI  - Peptide methionine sulfoxide reductase A (MsrA): direct electrochemical oxidation
      on carbon electrodes.
AB  - The direct electrochemical behaviour of peptide methionine sulfoxide reductase A
      (MsrA) adsorbed on glassy carbon and boron doped diamond electrodes surface, was
      studied over a wide pH range by cyclic and differential pulse voltammetry. MsrA
      oxidation mechanism occurs in three consecutive, pH dependent steps,
      corresponding to the oxidation of tyrosine, tryptophan and histidine amino acid
      residues. At the glassy carbon electrode, the first step corresponds to the
      oxidation of tyrosine and tryptophan residues and occurs for the same potential.
      The advantage of boron doped diamond electrode was to enable the separation of
      tyrosine and tryptophan oxidation peaks. On the second step occurs the histidine
      oxidation, and on the third, at higher potentials, the second tryptophan
      oxidation. MsrA adsorbs on the hydrophobic carbon electrode surface
      preferentially through the three hydrophobic domains, C1, C2 and C3, which
      contain the tyrosine, tryptophan and histidine residues, and tryptophan exists
      only in these regions, and undergo electrochemical oxidation.

PMID- 22967952
TI  - Ranking Gene Ontology terms for predicting non-classical secretory proteins in
      eukaryotes and prokaryotes.
AB  - Protein secretion is an important biological process for both eukaryotes and
      prokaryotes. Several sequence-based methods mainly rely on utilizing various
      types of complementary features to design accurate classifiers for predicting non
      classical secretory proteins. Gene Ontology (GO) terms are increasing informative
      in predicting protein functions. However, the number of used GO terms is often
      very large. For example, there are 60,020 GO terms used in the prediction method
      Euk-mPLoc 2.0 for subcellular localization. This study proposes a novel approach
      to identify a small set of m top-ranked GO terms served as the only type of input
      features to design a support vector machine (SVM) based method Sec-GO to predict
      non-classical secretory proteins in both eukaryotes and prokaryotes. To evaluate
      the Sec-GO method, two existing methods and their used datasets are adopted for
      performance comparisons. The Sec-GO method using m=436 GO terms yields an
      independent test accuracy of 96.7% on mammalian proteins, much better than the
      existing method SPRED (82.2%) which uses frequencies of tri-peptides and short
      peptides, secondary structure, and physicochemical properties as input features
      of a random forest classifier. Furthermore, when applying to Gram-positive
      bacterial proteins, the Sec-GO with m=158 GO terms has a test accuracy of 94.5%,
      superior to NClassG+ (90.0%) which uses SVM with several feature types,
      comprising amino acid composition, di-peptides, physicochemical properties and
      the position specific weighting matrix. Analysis of the distribution of secretory
      proteins in a GO database indicates the percentage of the non-classical secretory
      proteins annotated by GO is larger than that of classical secretory proteins in
      both eukaryotes and prokaryotes. Of the m top-ranked GO features, the top-four GO
      terms are all annotated by such subcellular locations as GO:0005576
      (Extracellular region). Additionally, the method Sec-GO is easily implemented and
      its web tool of prediction is available at iclab.life.nctu.edu.tw/secgo.

PMID- 22967953
TI  - The different proteomes of Chlamydomonas reinhardtii.
AB  - Protein identification and proteome mapping mostly rely on the combination of
      tandem mass spectrometry and sequence database searching. Despite constant
      improvements achieved in instrumentation, search algorithms, and genome
      annotations, little effort has been invested in estimating the impact of
      different genome annotation releases on the final results of a proteome study. We
      have used a large dataset of mass spectra obtained using an Orbitrap LTQ XL
      instrument, covering different growth situations of the model species
      Chlamydomonas reinhardtii. More than one million spectra were analyzed employing
      the SEQUEST algorithm and four different databases corresponding to the major
      Chlamydomonas genome assemblies. In total more than 3000 proteins and about
      11,000 peptides were identified. 238 proteins were exclusively detected in
      assembly 3.0 in contrast to 1222 missing proteins only detectable in other
      databases. The comparison of the results demonstrates that the database selection
      affects not only the number of identified proteins but also label free
      quantitation and the biological interpretation of the results. Lists of protein
      accessions exclusively assigned to individual C. reinhardtii genome assemblies
      and annotations are provided as a resource for proteogenomic studies.

PMID- 22967954
TI  - Immune competence of the Ciona intestinalis pharynx: complement system-mediated
      activity.
AB  - In the tunicate Ciona intestinalis, the ciliated pharynx, which connects the
      external environment to a highly developed and compartmentalized gastrointestinal
      system, represents the natural portal of entry for a vast and diverse,
      potentially pathogenic microbial community. To address the role of the pharynx in
      immune surveillance in Ciona, we asked whether C3, the key component of the
      complement system, was expressed in this organ and whether the encoded protein
      was functionally active. We found by real-time PCR that C3, constitutively
      expressed in the pharynx, is up-regulated by LPS injection. Using two specific
      anti-CiC3 and anti-CiC3a polyclonal antibodies in immunohistochemical staining of
      pharynx sections, we found that the gene product was localized to hemocytes of
      the pharyngeal bars (identified as granular amoebocytes) and in stigmata ciliated
      cells. Use of the same antibodies in Western blot analysis indicated that CiC3
      and its activation products CiC3b and CiC3a are present in pharynx homogenates.
      Our observation that the amount of the bioactive fragment CiC3a increased in the
      pharynx of LPS-treated animals provides the first molecular and functional
      evidence for complement-mediated immunological activity in the tunicate pharynx.

PMID- 22967955
TI  - Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo
      probe.
AB  - BACKGROUND: A new thromboembolic animal model showed beneficial effects of t-PA
      with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal
      experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in
      this mouse strain and measured infarct volume and vascular recanalisation in-vivo
      by using high-field 9.4 T MRI and a 1H surface cryo coil. METHODS: Clot formation
      was triggered by microinjection of murine thrombin into the right middle cerebral
      artery (MCA). Animals (n = 28) were treated with 10 mg/kg, 5 mg/kg or no tissue
      plasminogen activator (t-PA) 40 min after MCA occlusion. For MR-imaging a Bruker
      9.4 T animal system with a 1H surface cryo probe was used and a T2-weighted RARE
      sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated
      gradient echo TOF angiography were performed. RESULTS: The infarct volume in
      animals treated with t-PA was significantly reduced (0.67 +/- 1.38 mm3 for 10
      mg/kg and 10.9 +/- 8.79 mm3 for 5 mg/kg vs. 19.76 +/- 2.72 mm3 ; p < 0.001)
      compared to untreated mice. An additional group was reperfused with t-PA inside
      the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow
      was re-established in the right MCA. However, signal intensity was lower than in
      the contralateral MCA. This reduction in cerebral blood flow was attenuated
      during the first 60 minutes after reperfusion. 24 h after MCA occlusion and
      reperfusion, no difference in signal intensity of the contralateral and
      ipsilateral MCAs was observed. CONCLUSIONS: We confirm a t-Pa effect using this
      stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence
      MRI imaging after t-PA using a 1H surface cryo coil in a 9.4 T MRI. This setting
      will allow testing of new thrombolytic strategies for stroke treatment in-vivo in
      C57BL76 knock-out mice.

PMID- 22967956
TI  - Predicting first episode psychosis in those at high risk for genetic or cognitive
      reasons.
AB  - Structural and functional magnetic resonance imaging (MRI) of patients with
      psychosis has advanced to the point where there are clear abnormalities at a
      group level between patients and groups of healthy controls, and suggestions of
      different patterns of abnormalities between groups of patients. A major area of
      research endeavour is being able to translate these group differences into
      clinically relevant predictions at an individual patient level. Here, we briefly
      summarize our main findings in cohorts at high risk of psychosis because they
      come from families in which several members have schizophrenia or bipolar
      disorder, or have educational impairments. We highlight consistent predictors of
      psychosis in those at high risk of schizophrenia for genetic or cognitive
      reasons, as compared with quite distinct profiles between those at genetic high
      risk of schizophrenia v. bipolar disorder on functional MRI during an executive
      language task. We also consider future research directions and ethical issues in
      the early diagnostic testing of people at high risk of psychosis.

PMID- 22967957
TI  - Hesperetin ameliorates hyperglycemia induced retinal vasculopathy via anti
      angiogenic effects in experimental diabetic rats.
AB  - The purpose of the study was to evaluate vasculoprotective effects of Hesperetin
      (Hsp) in Streptozotocin induced diabetic rats. The study was carried out for a
      period of 24weeks and evaluated for angiogenic parameters (VEGF and PKC-beta),
      retinal vascular leakage by fluorescein angiography and, vessel (arteriolar and
      venular) diameters and any morphological abnormality through fundus photographs.
      Apart from this, transmission electron microscopy (TEM) was done to determine
      capillary basement membrane (BM) thickness. The results of the present study
      showed a significant increase in the expression of VEGF and PKC-beta in diabetic
      retinae as compared to normal retinae. On the other hand, Hsp-treated retinae
      showed marked inhibition in the expression of VEGF and PKC-beta. In the present
      study, diabetic retinae showed increase vascular permeability and leakage as
      compared to normal retinae. However, Hsp-treated retinae have not shown any such
      vascular dysfunctions. Moreover, there was significant increase in vessel caliber
      recorded in diabetic retinae compared to normal retinae, on the contrary Hsp
      treated retinae showed lesser dilated vessels. Further, TEM study showed
      thickened BM in diabetic group as compared to normal group. However, Hsp-treated
      retinae showed marked prevention in BM thickness. In conclusion, it can be sated
      that Hsp has potential vasoprotective effects and can be useful in preventing
      diabetes induced vasculopathy.

PMID- 22967958
TI  - Anatomy of the kisspeptin systems in teleosts.
AB  - Kisspeptin and its cognate receptor, GPR54 (kisspeptin receptor, Kiss-R) have
      recently been recognized potent regulators of reproduction in vertebrates. In non
      mammalian vertebrates, kisspeptin-Kiss-R homologous and paralogous genes have
      been identified with their conserved functions in reproduction. Teleosts possess
      two paralogous genes encoding kisspeptin (kiss1 and kiss2) and Kiss-R (kissr1 and
      kissr2). Identification of the location and the distribution of the kisspeptin
      Kiss-R systems as well as their connectivity with other neural system in the
      brain is important to elucidate the role of kisspeptin in neuroendocrine
      functions. This review focuses on the comparative aspects of neuroanatomical
      distribution of two kisspeptin-Kiss-R systems in the brain of teleosts and their
      potential roles in reproductive and non-reproductive functions. Finally, based on
      the association of kisspeptin types with tachykinin peptides, their potential
      neuromodulatory roles in the brain of teleost will be discussed. The existence of
      two kisspeptin systems suggests their independent functions in the brain of
      teleosts. Understanding of teleosts Kiss1 and Kiss2 systems will provide insight
      into the physiological and evolutional significance of multiple kisspeptin
      systems in the vertebrate brain.

PMID- 22967959
TI  - Reproductive cycle of free-living male Saharan sand vipers, Cerastes vipera
      (Viperidae) in the Negev desert, Israel.
AB  - The Saharan sand viper, Cerastes vipera (Linnaeus, 1758), is distributed in all
      Saharan countries, being confined to sand and dune systems. This relatively small
      snake, up to 35 cm, is nocturnal, is active from spring to autumn (April to
      October) and hibernates during the winter (November to March). We predicted that
      C. vipera would have peak plasma testosterone concentration at mating and that
      the vas deferens would contain abundant spermatozoa at that time. To test our
      predictions, we collected information on the time of mating and measured monthly
      testosterone concentration, testes size and testicular activity in free-living
      male C. vipera during its active period from April to October. Mating occurred
      only during spring. The pattern of plasma testosterone concentration, testes
      volume, seminiferous tubule diameter and spermatogenesis all followed the general
      pattern of high values in autumn and spring and low values in early summer. Our
      predictions were partially supported. There was a high plasma testosterone
      concentration at mating in spring and the vas deferens contained abundant
      spermatozoa, as predicted, but there was also a high plasma testosterone
      concentration in autumn without mating. We concluded that: (1) males are both
      aestival in that they produce spermatozoa in autumn, which they store over the
      winter hibernation period, and vernal in that they produce spermatozoa in spring
      prior to mating; (2) matings are associated with spermatogenesis; and (3) the
      high plasma testosterone concentration is concomitant with both matings and
      spermatogenesis in spring and with spermatogenesis in autumn. We propose that C.
      vipera has a single peak of testicular activity and plasma testosterone
      concentration which start in autumn and end in spring. We also propose that
      spermatogenesis is prior to spring mating and, consequently, is prenuptial.

PMID- 22967961
TI  - The option of delayed reconstructive surgery following mastectomy for invasive
      breast cancer: why do so few patients embrace this offer?
AB  - BACKGROUND: Only a minority of patients who had undergone mastectomy for invasive
      breast cancer (BC) chose the option for delayed breast reconstruction (BR). We
      hypothesized that this might partly be (a) due to a lack of information, or (b)
      because many women cope well with their altered body. METHODS: A cross-sectional
      survey was completed by 101 early-stage BC survivors who had primary mastectomy.
      Twenty-six patients had delayed BR. The survey included measures to attitudes to
      BR and experiences/expectations about information related to BR. RESULTS: The
      percentage of patients who was informed regarding BR was high (97%). For 39.5%
      such information was not considered important, neither before mastectomy, nor
      during follow-up; advanced age was an important factor for the disinterest in
      information (odds ratio 1.81; 95% CI: 1.04-3.16; p = 0.033). For women without
      BR, the perception that mastectomy caused a serious damage to their body image
      changed over time to perceiving the operation as an acceptable alteration of the
      body (-1.10; 95% CI, -1.52, -0.64; p < 0.001); this process was similar to that
      in patients who had BR (paired t-test: -2.12; 95% CI, -2.82, -1.41; p > 0.001).
      From 63 patients who reported no intention to have a BR in the future, 28 (44.4%)
      responded with answers that showed a high satisfaction with their mastectomies
      without BR; 30 patients (47.6%) reported reasons, which might potentially be
      dispelled by information by an experienced reconstructive surgeon. CONCLUSIONS:
      We did not find any evidence that the low number of patients who chose delayed BR
      results from a lack of information regarding this procedure. The majority of
      patients overcome negative attitudes towards their mastectomy quickly and are
      uninterested in BR. Patients who are ambivalent must be identified; these women
      require particular attention and should receive intensive counseling.

PMID- 22967960
TI  - Proliferation in the normal FTE is a hallmark of the follicular phase, not BRCA
      mutation status.
AB  - PURPOSE: Women who have inherited germline mutations of BRCA1/BRCA2 are at
      increased risk of developing high-grade serous carcinoma, and many of these
      cancers arise in the distal fimbriated end of the fallopian tube. We have
      previously shown that the fallopian tube epithelia of BRCA1 mutation carriers
      (FTE-BRCA) have altered signaling pathways compared to nonmutation carriers. In
      this study, we sought to determine whether these differences result in a
      proliferative advantage to the epithelia in this high-risk patient population and
      to investigate whether the postovulation environment of the FTE-BRCA compared to
      FTE from nonmutation carriers experiences a differential abundance of immune
      cells. METHOD: Immunohistochemistry for Ki67, CD3, CD8, CD20, and CD68 was
      performed on histologically normal tubal epithelium (ampulla, n = 83), fimbria (n
      = 18) with known ovarian cycle status and germline mutation status and for Ki67
      on fimbrial epithelium from women (n = 144) with and without BRCA1 or BRCA2
      mutations who underwent risk-reducing salpingo-oophorectomy (RRSO). Serous tubal
      intraepithelial carcinomas (STIC) with concomitant cancer (n = 15) were also
      analyzed for presence of immune infiltrates. All slides were digitized and
      analyzed using automated image analysis software. RESULTS: There was no
      significant difference in the proliferative index in histologically normal FTE
      between BRCA1/BRCA2 and non-BRCA, in 144 fimbriae and 83 ampullae. The FTE-BRCA1
      epithelia did not exhibit a differential presence of lymphocytes or macrophages,
      however more macrophages were present in the luteal phase compared to the
      follicular phase epithelia. In STICs macrophages were more abundant than
      lymphocytes with an incremental increase noted with disease progression.
      CONCLUSIONS: BRCA1/2 mutation carriers exhibited no significant increase in
      proliferation in the fallopian tube epithelial cells either in the ampulla or
      fimbriated ends of the tube. Rather, a significant proliferative increase was
      defined in the cases determined to be in the follicular, or proliferative,
      preovulatory phase of the ovarian cycle. Finally, we also show an incremental
      increase in leukocytes invading the STICs and HGSC, implicating a possible role
      of the leukocytes early in the progression or inhibition of tumor formation,
      which is independent of ovarian cycle status.

PMID- 22967962
TI  - Age-related Epstein-Barr virus-positive cutaneous ulcer arising after a self
      limited subcutaneous abscess: a case report.
AB  - INTRODUCTION: Epstein-Barr virus-positive mucocutaneous ulcer is a newly
      recognized clinicopathologic entity in the spectrum of Epstein-Barr virus
      positive lymphoproliferative disorders. This entity is characterized by a self
      limited, indolent course. CASE PRESENTATION: We report the case of a 74-year-old,
      type 2 diabetic man who presented with an ulceroinfiltrative skin lesion on the
      left side of his neck. Histological examination showed that the lesion consisted
      of large atypical cells, some with Hodgkin-Reed-Sternberg-like morphology, in the
      midst of reactive lymphocytes, plasma cells, eosinophils and histiocytes. The
      atypical cells were partially positive for CD45, CD20, CD79a, CD30, B-cell
      lymphoma 2 and latent membrane protein 1 (CS.1-4), and negative for CD15, B-cell
      lymphoma 6 and CD10. In situ hybridization for Epstein-Barr virus-encoded
      ribonucleic acid was positive. Two years before, the patient had been diagnosed
      with a self-limited subcutaneous abscess in the same anatomic area that healed
      after antibiotic therapy. CONCLUSION: Older patients with positive Epstein-Barr
      virus serology may develop B-cell lymphoproliferations due to age-related immune
      suppression. Epstein-Barr virus-encoded ribonucleic acid testing and clonality
      analysis, eventually complemented with close clinical follow-up, should be
      performed for suspicious inflammatory lesions in older patients.

PMID- 22967963
TI  - A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on
      incidence of vertebral fractures, either directly or through non-linear changes
      in bone mass density.
AB  - BACKGROUND/AIMS: Bone mass density values have been related with risk of
      vertebral fractures in post-menopausal women. However, bone mass density is not
      perfectly accurate in predicting risk of fracture, which decreases its usefulness
      as a surrogate in clinical trials. We propose a modeling framework with three
      interconnected parts to improve the evaluation of bone mass density accuracy in
      forecasting fractures after treatment. METHODS: The modeling framework includes:
      (1) a piecewise regression to describe non-linear temporal BMD changes more
      accurately than crude percent changes, (2) a structural equation model to analyze
      interdependencies among vertebral fractures and their potential risk factors in
      preference to regression techniques that consider only directional associations,
      and (3) a counterfactual causal interpretation of the direct and indirect
      relationships between treatment and occurrence of vertebral fractures. We apply
      the methods to BMD repeated measurements from a study of the effect of
      bazedoxifene acetate on incident vertebral fractures in three different
      geographical regions. RESULTS: We made four observations: (1) bone mass density
      changes varied largely across participants, (2) baseline age and body mass index
      influenced baseline bone mass density that, in turn, had an effect on prevalent
      fractures, (3) direct and/or indirect effects of bazedoxifene acetate on incident
      fractures were different across regions, and (4) estimates of indirect effects
      were sensible to the presence of post-treatment unmeasured confounders. In one
      region, around 40% of the bazedoxifene acetate effect on the occurrence of
      fracture is explained by its effect on bone mass density. Under the
      counterfactual approach, these 40% represent the average difference in the
      occurrence of fracture observed for untreated individuals when their bone mass
      density values are set at the value under bazedoxifene acetate versus under
      placebo. CONCLUSIONS: Computational methods are available to evaluate and
      interpret the surrogacytic capability of a biomarker of a primary outcome.

PMID- 22967964
TI  - 2-Methylbutyrylglycine induces lipid oxidative damage and decreases the
      antioxidant defenses in rat brain.
AB  - Short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency is an autosomal
      recessive disorder of isoleucine metabolism biochemically characterized by
      accumulation of 2-methylbutyrylglycine (2MBG) and 2-methylbutyric acid (2MB).
      Affected patients present predominantly neurological symptoms, whose
      pathophysiology is not yet established. In the present study, we investigated the
      in vitro effects of 2MBG and 2MB on important parameters of oxidative stress in
      cerebral cortex of young rats and C6 glioma cells. 2MBG increased thiobarbituric
      acid-reactive species (TBA-RS), indicating an increase of lipid oxidation. 2MBG
      induced sulfhydryl oxidation in cortical supernatants and decreased glutathione
      (GSH) in these brain preparations, as well as in C6 cells, indicating a reduction
      of nonenzymatic brain antioxidant defenses. In contrast, 2MB did not alter any of
      these parameters and 2MBG and 2MB did not affect carbonyl formation (protein
      damage). In addition, 2MBG-induced increase of TBA-RS levels and decrease of GSH
      were prevented by free radical scavengers, implying that reactive species were
      involved in these effects. Furthermore, the decrease of GSH levels caused by 2MBG
      was not due to a direct oxidative action since this metabolite did not alter
      sulfhydryl content from a commercial solution of GSH. Nitric oxide production was
      not altered by 2MBG and 2MB, suggesting that reactive oxygen species possibly
      underlie 2MBG effects. Finally, we verified that 2MBG did not induce cell death
      in C6 cells. The present data show that 2MBG induces lipid oxidative damage and
      reduces the antioxidant defenses in rat brain. Therefore, it may be postulated
      that oxidative stress induced by 2MBG is involved, at least in part, in the
      pathophysiology of the brain damage found in SBCAD deficiency.

PMID- 22967965
TI  - Outcome of patients with early stage oral cancer managed by an observation
      strategy towards the N0 neck using ultrasound guided fine needle aspiration
      cytology: No survival difference as compared to elective neck dissection.
AB  - OBJECTIVES: Management of the clinically N0 neck in oral cancer patients remains
      controversial. We describe the outcome of patients with T1-T2 oral cancer and N0
      neck based on ultrasound guided fine needle aspiration cytology (USgFNAC) who
      were treated by transoral excision and followed by a 'wait and scan' policy
      (W&S). PATIENTS AND METHODS: This retrospective analysis included 285 consecutive
      patients of whom 234 were followed by W&S and 51 underwent elective neck
      dissection (END). Survival rates were compared between groups and correction for
      confounding factors was performed. RESULTS: Of W&S patients, the 5-year disease
      specific (DSS) and overall survival (OS) were 94.2% and 81.6% respectively.
      During follow-up 72.2% remained free of lymph node metastases and 27.8% developed
      delayed metastases. W&S patients with delayed metastases had a 5-year DSS and OS
      of 80.0% and 62.8%, respectively. In patients with positive END these rates were
      81.3% and 64.2%, respectively. Between the groups, survival rates were not
      significantly different. Of the W&S patients with delayed metastases, 90.6%
      needed adjuvant radiotherapy versus 55.0% of patients with positive END.
      CONCLUSION: With regard to survival, in patients with early stage oral cancer and
      cN0 neck a 'wait and scan' policy using strict USgFNAC surveillance is justified
      as survival is not negatively influenced. Using a 'wait and scan' follow-up
      strategy instead of elective neck treatment, unnecessary neck dissection and its
      accompanying morbidity can be avoided in 72.2% of patients. However, for the
      small proportion of patients with delayed metastases, more extensive treatment
      with adjuvant radiotherapy is needed.

PMID- 22967966
TI  - Effects of the propeptide of group X secreted phospholipase A(2) on substrate
      specificity and interfacial activity on phospholipid monolayers.
AB  - Group X secreted phospholipase A(2) (GX sPLA(2)) plays important physiological
      roles in the gastrointestinal tract, in immune and sperm cells and is involved in
      several types of inflammatory diseases. It is secreted either as a mature enzyme
      or as a mixture of proenzyme (with a basic 11 amino acid propeptide) and mature
      enzyme. The role of the propeptide in the repression of sPLA(2) activity has been
      studied extensively using liposomes and micelles as model interfaces. These
      substrates are however not always suitable for detecting some fine tuning of
      lipolytic enzymes. In the present study, the monolayer technique is used to
      compare PLA(2) activity of recombinant mouse GX sPLA(2) (mGX) and its pro-form
      (PromGX) on monomolecular films of dilauroyl-phosphatidyl-ethanolamine (DLPE), 
      choline (DLPC) and -glycerol (DLPG). The PLA(2) activity and substrate
      specificity of mGX (PE ~ PG > PC) were found to be surface pressure-dependent.
      mGX displayed a high activity on DLPE and DLPG but not on DLPC monolayers up to
      surface pressures corresponding to the lateral pressure of biological membranes
      (30-35 mN/m). Overall, the propeptide impaired the enzyme activity, particularly
      on DLPE whatever the surface pressure. However some conditions could be found
      where the propeptide had little effects on the repression of PLA(2) activity. In
      particular, both PromGX and mGX had similar activities on DLPG at a surface
      pressure of 30 mN/m. These findings show that PromGX can be potentially active
      depending on the presentation of the substrate (i.e., lipid packing) and one
      cannot exclude such an activity in a physiological context. A structural model of
      PromGX was built to investigate how the propeptide controls the activity of GX
      sPLA(2). This model shows that the propeptide is located within the interfacial
      binding site (i-face) and could disrupt both the interfacial binding of the
      enzyme and the access to the active site by steric hindrance.

PMID- 22967967
TI  - Electron-phonon relaxation and excited electron distribution in zinc oxide and
      anatase.
AB  - We propose a first-principles method for evaluations of the time-dependent
      electron distribution function of excited electrons in the conduction band of
      semiconductors. The method takes into account the excitations of electrons by an
      external source and the relaxation to the bottom of the conduction band via
      electron-phonon coupling. The methods permit calculations of the non-equilibrium
      electron distribution function, the quasi-stationary distribution function with a
      steady-in-time source of light, the time of setting of the quasi-stationary
      distribution and the time of energy loss via relaxation to the bottom of the
      conduction band. The actual calculations have been performed for titanium dioxide
      in the anatase structure and zinc oxide in the wurtzite structure. We find that
      the quasi-stationary electron distribution function has a peak near the bottom of
      the conduction band and a tail whose maximum energy rises linearly with
      increasing energy of excitation. The calculations demonstrate that the relaxation
      of excited electrons and the setting of the quasi-stationary distribution occur
      within a time of no more than 500 fs for ZnO and 100 fs for anatase. We also
      discuss the applicability of the effective phonon model to energy-independent
      electron-phonon transition probability. We find that the model only reproduces
      the trends in the change of the characteristic times whereas the precision of
      such calculations is not high. The rate of energy transfer to phonons at the
      quasi-stationary electron distribution also have been evaluated and the effect of
      this transfer on the photocatalysis has been discussed. We found that for ZnO
      this rate is about five times less than in anatase.

PMID- 22967968
TI  - [Lay emphasis on the treatment of massive burn casualties in conflagration].
AB  - Burn surgery belongs to disaster medicine. Burn is a common trauma that occurs in
      social activities of human beings in all ages, either in the time of peace or
      war. During the development of human medicine in modern times, the summary of
      experience in treating massive burn casualties due to severe fire accidents has
      effectively promoted the renovation of treating technology and theory of burns
      and the development of burn surgery. The results of treatment of burn injury in
      casualties occurred in the fire of Cocoanut Grove night club in Boston in 1942,
      and the high-rise apartment house fire in Shanghai in 2010 were summarized and
      analyzed in this article, emphasizing the correlating issues of inhalation
      injury.

PMID- 22967969
TI  - [Comparative study on the effect of restrictive fluid management strategy on the
      early pulmonary function of patients with severe burn].
AB  - OBJECTIVE: To retrospectively analyze the effect of restrictive fluid management
      strategy (RFMS) on the early pulmonary function and the prognosis of patients
      with extremely severe and extensive burn. METHODS: Thirteen patients with
      extremely severe burn hospitalized from June 2010 to November 2011, being treated
      with RFMS in the fluid reabsorption stage, were enrolled as treatment group.
      Twenty-six patients with extremely severe burn hospitalized from March 2008 to
      November 2011, being treated with normal fluid therapy in the fluid reabsorption
      stage, were enrolled as control group. The match proportion between treatment
      group and control group was 1:2. Fluid intake, fluid output, fluid balance (the
      difference between fluid intake and output), and plasma albumin level from post
      burn day (PBD) 3 to 10, pulmonary oxygenation index on PBD 3, 5, 7, 10, and 14,
      occurrence of lung and blood stream infections from PBD 7 to 14, and occurrence
      of acute respiratory distress syndrome (ARDS), occurrence of other organ
      complications, and mortality within 2 weeks post burn (PBW) were recorded and
      compared. Measurement data were processed with t test and randomized blocks
      analysis of variance, enumeration data were processed with Fisher's exact test.
      RESULTS: Daily fluid intake of patients showed a tendency of decrease in both
      groups from PBD 3 to 10. Except for that of PBD 4, there was no statistically
      significant difference between two groups in fluid intake (with F values from
      0.072 to 1.939, P values all above 0.05). Daily fluid output of patients showed a
      tendency of increase in both groups from PBD 3 to 10. It peaked on PBD 10 in
      control group and PBD 6 in treatment group. The mean daily fluid output was
      higher in treatment group than in control group from PBD 4 to 9, but without
      statistically significant difference (with F values from 0.001 to 3.026, P values
      all above 0.05). Fluid balance lowered in both groups, and it was the lowest on
      PBD 10 in control group and PBD 6 in treatment group. Fluid balance was lower in
      treatment group than in control group from PBD 3 to 7, and it showed
      statistically significant differences on PBD 4, 5, and 6 (with F values from
      4.799 to 8.031, P values below 0.05). Plasma albumin level was higher in
      treatment group than in control group from PBD 3 to 10, with statistically
      significant differences observed on PBD 4, 9, and 10 (with F values from 5.691 to
      10.551, P < 0.05 or P < 0.01). Pulmonary oxygenation index was higher in
      treatment group than in control group from PBD 3 to 14, with statistically
      significant differences observed on PBD 7 (respectively 372 +/- 78 in treatment
      group and 291 +/- 92 in control group, F = 5.184, P < 0.05) and 14 (respectively
      354 +/- 39 in treatment group and 283 +/- 72 in control group, F = 8.683, P <
      0.05). Lung infection and blood stream infection were respectively observed in 1
      and 4 patient (s) in treatment group, and 9 and 11 patients in control group from
      PBD 7 to 14. Occurrence of ARDS, occurrence of other organ complications, and
      mortality were fewer in treatment group than in control group within PBW 2,
      though the differences were not statistically significant (P values all above
      0.05). CONCLUSIONS: RFMS is a useful strategy in improving early pulmonary
      oxygenation of patients with extremely severe and extensive burn by promoting the
      process of fluid reabsorption and rebalance. This strategy may be also beneficial
      for the prevention of organ complications as well as a better prognosis in
      severely burned patients.

PMID- 22967971
TI  - [Influence of high-voltage electric burn on the microcirculation of heart in
      rabbit].
AB  - OBJECTIVE: To study the influence of high-voltage electric burn on the
      microcirculation of heart in rabbit. METHODS: One-hundred and twenty New Zealand
      rabbits of clean grade were divided into control group (C) and electric burn
      group (EB) according to the random number table, with 60 rabbits in each group.
      Rabbits in EB group were subjected to high-voltage electric burn (the electrical
      current flow into the left foreleg at the lateral side of proximal end and out
      from the corresponding site of the right hind leg) with voltage regulator and
      experimental transformer. Rabbits in C group were sham injured with the same
      devices without electrification. At 15 minutes before injury, and 5 minutes, 1,
      2, 4, 8 hour (s) post injury (PIM or PIH), ten rabbits in each group were chosen
      to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser
      Doppler hemoperfusion image instrument. The morphologic changes of microvessels
      of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits
      collected at above-mentioned time points were observed with light microscope and
      transmission electron microscope. Auricular vein blood of rabbit was harvested at
      above-mentioned time points for the determination of aspartate amino transferase
      (AST), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH),
      creatine kinase (CK), and creatine kinase isozyme MB (CK-MB) by full-automatic
      biochemical analyzer. Data were processed with two-factor analysis of variance
      and LSD test. RESULTS: (1) The differences between C group and EB group in
      detection results were statistically significant, with F values from 425.991 to
      3046.834, P values all below 0.01. Only the data within EB group were comparable.
      (2) At PIM 5, the CAMH value of rabbits in EB group was (1.96 +/- 0.09) V, which
      was lower than that at 15 minutes before injury [(4.34 +/- 0.35) V, P < 0.01].
      The CAMH value of rabbits in EB group was increased at PIH 1 [(3.43 +/- 0.30) V],
      and then it showed a tendency of decrease. (3) Bleeding and microthrombus
      formation were observed in venule and capillary vessel of rabbits in EB group at
      PIH 8. Breakage of basement membrane of capillary endothelial cells,
      mitochondrial swelling, and severe degranulation from damaged endoplasmic
      reticulum were observed in rabbits of EB group at PIH 8. (4) Levels of AST, LDH,
      HBDH, CK, and CK-MB in rabbits of EB group were significantly higher at PIH 1, 2,
      4, 8 than at 15 minutes before injury (with P values all below 0.01). The AST
      level peaked at PIH 2 [(164 +/- 39) U/L]. Levels of LDH and HBDH peaked at PIH 4,
      which were respectively (1016 +/- 246) U/L and (487 +/- 54) U/L. The CK level
      peaked at PIH 8 [(7799 +/- 738) U/L]. The CK-MB level peaked at PIH 2 [(1848 +/-
      65) U/L]. CONCLUSIONS: High-voltage electric burn can bring damage to the
      microvessels of heart in rabbits and change blood flow of microcirculation, which
      should be given adequate attention during the treatment.

PMID- 22967972
TI  - [Application of Narcotrend-assisted anesthesia in-depth monitor during
      escharectomy and skin transplantation in burn patients with target-controlled
      infusion of remifentanil hydrochloride and propofol].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of Narcotrend (NT) monitor in
      monitoring the depth of anesthesia in severely burned patients with target
      controlled infusion (TCI) of remifentanil hydrochloride and propofol during
      perioperative period. METHODS: Eighty patients with severe burn hospitalized from
      February to November 2011, to whom eschar excision was performed within one week
      after injury, were enrolled. They were classified into II to III grade according
      to the American Society of Anesthetists classification, and their total burn area
      ranged from 31% to 50%TBSA, or full-thickness burn area from 11% to 20% TBSA.
      Patients were divided into trial group (monitoring depth of anesthesia with
      routine method and NT monitor) and control group (monitoring depth of anesthesia
      with routine method) according to the random number table, with 40 cases in each
      group. All patients received TCI of remifentanil hydrochloride and propofol to
      induce and maintain anesthesia. During the operation, the anesthesia level of NT
      monitor used in the trial group was maintained from grade D1 to E0, while the
      fluctuation of mean arterial pressure (MAP) and heart rate of patients in control
      group was maintained around the basic values within a range of 20%, and on the
      basis of which, concentrations of two narcotics were adjusted. Concentrations of
      remifentanil hydrochloride and propofol during maintenance of anesthesia were
      recorded. The duration from drug withdrawal to waking from anesthesia (including
      the duration from drug withdrawal to eye opening by calling and the duration from
      drug withdrawal to orientation recovery) of patients was recorded. Values of MAP
      and heart rate at admission into the operation room, loss of consciousness, 2 min
      after intubation, before operation, 2, 15, and 30 min after the beginning of
      operation, and the end of operation were recorded. The prediction probability
      (P(k)) of NT stage (NTS) and NT index (NTI) in trial group, and that of MAP and
      heart rate in control group for two durations from drug withdrawal to waking form
      anesthesia were recorded. The administration of vasoactive drugs and
      intraoperative awareness of patients in two groups were recorded. Data were
      processed with t test, analysis of variance, and chi-square test, and the
      relationship between NTS, NTI, MAP, heart rate and their corresponding P(k) for
      the duration from drug withdrawal to orientation recovery was processed with
      Spearman correlation analysis. RESULTS: Maintained target effect-site
      concentration of remifentanil hydrochloride and target plasma concentration of
      propofol of patients were obviously lower in trial group [(2.62 +/- 0.35) ng/mL,
      (3.84 +/- 0.22) ug/mL] than in control group [(2.95 +/- 0.21) ng/mL, (4.16 +/-
      0.31) ug/mL, with t values respectively -5.113 and -5.324, P values all below
      0.01]. The duration from drug withdrawal to eye opening by calling and the
      duration from drug withdrawal to orientation recovery were obviously shorter in
      trial group [(10.2 +/- 0.7) min, (11.1 +/- 1.0) min] than in control group [(11.3
      +/- 1.0) min, (13.1 +/- 0.7) min, with t values respectively -5.740 and -10.806,
      P values all below 0.01]. The MAP (except for 2 min after intubation) and the
      heart rate of patients in both groups were lower at the time points from loss of
      consciousness to the end of operation than at the time of entering operation room
      (with F values respectively 12.074, 36.425, P values all below 0.01 in trial
      group and F values respectively 21.776, 35.759, P values all below 0.01 in
      control group). The statistically significant difference between two groups in
      MAP level was only observed at the time of loss of consciousness (t = 3.985, P <
      0.01). MAP level was close in two groups at other time points. Heart rates of
      patients in two groups were close during perioperative period. P(k) values of NTS
      and NTI for the duration from drug withdrawal to eye opening by calling (0.937 +/
      0.025, 0.899 +/- 0.049) were obviously higher than those of MAP and heart rate
      for this duration (0.579 +/- 0.057, 0.536 +/- 0.039, F = 900.337, P < 0.01). P(k)
      values of NTS and NTI for the duration from drug withdrawal to the orientation
      recovery (0.901 +/- 0.031, 0.868 +/- 0.046) were significantly higher than those
      of MAP and heart rate for this duration (0.532 +/- 0.060, 0.483 +/- 0.044, F =
      890.895, P < 0.01). NTS, NTI, MAP, and heart rate were respectively negative,
      positive, positive and positive in correlation with their P(k) values for the
      duration from drug withdrawal to the orientation recovery (with r values from 
      0.734 to 0.682, P values all below 0.01). There was no statistically significant
      difference between two groups in administration of vasoactive drugs. No
      intraoperative awareness occurred. CONCLUSIONS: Application of Narcotrend monitor
      in monitoring the depth of anesthesia in severely burned patients during
      perioperative period with TCI of remifentanil hydrochloride and propofol is
      beneficial to reducing dosage of narcotics and shortening duration of recovery
      from anesthesia, and it can accurately predict the level of consciousness of
      patients at the time of withdrawal of anesthesia.

PMID- 22967970
TI  - [Effect of salvia miltiorrhiza and Ligustrazine injection on the early myocardial
      damage of patients with severe burn].
AB  - OBJECTIVE: To observe the effect of salvia miltiorrhiza and ligustrazine
      injection on the early myocardial damage of severely burned patients. METHODS:
      Twenty severely burned patients hospitalized from January 2010 to August 2011,
      with burn area equal to or more than 50% TBSA, were divided into two groups
      following hospitalization sequence, with odd number patients entering treatment
      group (T, n = 10) and even number patients entering control group (C, n = 10).
      Patients in C group were treated with routine methods, including fluid
      resuscitation based on the Third Military Medical University formula, anti
      infection treatment, support treatment, and organ-protection treatment, etc. In
      addition to routine treatment methods, patients in T group received intravenous
      infusion of 250 mL glucose injection (50 g/L) containing 10 mL salvia
      miltiorrhiza and ligustrazine concoction, once a day, and continued for three
      days. Venous blood of patients was drawn at post burn hour (PBH) 12, 24, 48, and
      72 to determine the plasma levels of cardiac troponin I (cTnI), creatine kinase
      isozyme MB (CK-MB), and atrial natriuretic peptide (ANP). Data were processed
      with t test. RESULTS: At each time point, levels of cTnI, CK-MB, and ANP were
      lower in T group than in C group. Differences in contents of these parameters
      between two groups were statistically significant at most time points, with t
      values from 2.136 to 2.918, P < 0.05 or P < 0.01. Plasma levels of cTnI, CK-MB,
      and ANP in both groups peaked at PBH 12, which were respectively (28 +/- 10)
      ng/mL, (76 +/- 13) U/L, (430 +/- 87) pg/mL in T group, and (38 +/- 11) ng/mL, (87
      +/- 10) U/L, (453 +/- 91) pg/mL in C group. From PBH 24 to 72, contents of above
      mentioned parameters decreased gradually in both groups. CONCLUSIONS: Early use
      of salvia miltiorrhiza and ligustrazine injection in severely burned patients can
      effectively reduce myocardial damage, thus protect the myocardium from injury.

PMID- 22967973
TI  - [Advancement in the research of mechanism of endogenous cellular injury in
      visceral complications as complications after severe burn].
AB  - It is of great importance to know the endogenous mechanism in burn-induced organ
      injuries, not only for the understanding of pathophysiological processes after
      burn, but also for guiding the clinical treatment. Recent studies have widened
      and deepened our scope and understanding of secondary injuries to various organs.
      However, a unanimous understanding of molecular pathway involved in all burn
      induced organ injuries has not been attained. Relatively, the mechanism of
      endogenous cellular injuries as a result of burn injury could be regarded as a
      common one to explain the causation of cellular injury, and to guide the
      prevention and treatment for the burn-induced complications using cytoprotection
      strategy. This review summarized four aspects of the mechanism of endogenous
      cellular injuries, including cellular injuries induced by ischemic/hypoxic
      oxidative stress, excessive inflammatory factors released by inflammatory cells,
      immunosuppression caused by suppression of function of adaptive immune cells, and
      dysfunction of important supportive cells of various organs.

PMID- 22967974
TI  - [Wound information management system: a standardized scheme for acquisition,
      storage and management of wound information].
AB  - OBJECTIVE: To form a wound information management scheme with objectivity,
      standardization, and convenience by means of wound information management system.
      METHODS: A wound information management system was set up with the acquisition
      terminal, the defined wound description, the data bank, and related softwares.
      The efficacy of this system was evaluated in clinical practice. RESULTS: The
      acquisition terminal was composed of the third generation mobile phone and the
      software. It was feasible to get access to the wound information, including
      description, image, and therapeutic plan from the data bank by mobile phone.
      During 4 months, a collection of a total of 232 wound treatment information was
      entered, and accordingly standardized data of 38 patients were formed
      automatically. CONCLUSIONS: This system can provide standardized wound
      information management by standardized techniques of acquisition, transmission,
      and storage of wound information. It can be used widely in hospitals, especially
      primary medical institutions. Data resource of the system makes it possible for
      epidemiological study with large sample size in future.

PMID- 22967975
TI  - [Experimental study on the recycling of denatured acellular dermal matrix after
      burn].
AB  - OBJECTIVE: To explore the feasibility of burn denatured acellular dermal matrix
      (DADM) as dermal substitute in repairing wounds. METHODS: (1) Nine Wistar rats
      received a deep partial-thickness scald on the back. Full-thickness wounded skin
      was collected on post scald day (PBD) 1, 2, and 3 (with 3 rats at each time
      point), and it was treated with 2.5 g/L trypsin/0.5% Triton X-100 to remove cells
      to prepare DADM, respectively called DADM-1 d, DADM-2 d, and DADM-3 d. Another 3
      rats without scald injury were treated with the same method as above to prepare
      acellular dermal matrix (ADM) to serve as control. Gross and histological
      observations and microbiological and biomechanical tests, including ultimate
      tensile strength, maximum tension, stretched length at breaking, stress-strain
      relationship, were conducted for the resulting ADM and DADM. (2) Another 64 rats
      were divided into ADM group and DADM-1 d, DADM-2 d, and DADM-3 d groups according
      to the random number table, with 16 rats in each group. A skin flap in size of
      2.0 cm*1.8 cm was raised on the back of each rat. The above-mentioned ADM, DADM-1
      d, DADM-2 d, and DADM-3 d were cut into pieces in the size of 1.8 cm*1.5 cm, and
      they were respectively implanted under the skin flaps of rats in corresponding
      group. At post surgery week (PSW) 1, 3, 5, or 9, 4 rats in each group were used
      to observe wound healing condition and change in implants with naked eye, and
      histological observation of the implants was conducted. Data were processed with
      one-way analysis of variance and t test. RESULTS: (1) The freshly prepared DADM
      was milky white, soft in texture with flexibility, but poor in elasticity as
      compared with ADM. No epithelial structure or cellular component was observed in
      ADM or DADM under light microscope. Collagen fibers of DADM were seen to be
      thickened unevenly and arranged in disorder and eosinophilic. All microbiological
      results of DADM were negative. There was no statistically significant difference
      among DADM-1 d, DADM-2 d, and DADM-3 d in levels of ultimate tensile strength,
      maximum tension, stretched length at breaking, and stress-strain relationship
      (with F values from 0.088 to 3.591, P values all above 0.05). Values of the above
      mentioned four indexes were the highest in DADM-3 d, they were respectively (13.0
      +/- 2.4) MPa, (61 +/- 4) N, (173 +/- 7)%, (45.7 +/- 2.0)%. Values of the four
      indexes of ADM were respectively (19.0 +/- 2.6) MPa, (95 +/- 4) N, (201 +/- 5)%,
      (62.5 +/- 2.2)%, which were higher than those of DADM-1 d, DADM-2 d, and DADM-3 d
      (with t values from 6.424 to 17.125, P values all below 0.01). (2) No exudate or
      swelling in the wounds of rats, and no contraction or curling of implants were
      observed in every group at PSW 1, but inflammatory cells infiltration and Fbs
      inward migration were observed in the wound. At PSW 3, the growth of hair was
      normal in the wound in DADM-1 d, DADM-2 d, and ADM groups, but few and scattered
      hair grew in DADM-3 d group. The inflammatory cells decreased, while Fbs
      increased, and new capillaries were found to grow inwardly in each group. The
      decrease in inflammatory cells was slightly delayed in DADM-3 d group. At PSW 5,
      hair growth became normal, and implants shrank and thinned with fiber membrane
      wrapped densely and bundles of ingrowing large caliber blood vessels in all
      groups. The dermal matrix in each group merged with the surrounding normal
      tissue. At PSW 9, ADM and DADM became white, thin, and soft tissue sheet which
      was closely connected with the inner side of the flap. There was no infiltration
      of inflammatory cells in implants in either group. The collagen fibers arranged
      regularly and densely, and they were integrated with normal collagen tissue.
      CONCLUSIONS: The burned DADM does not have obvious immunogenicity, but with good
      biocompatibility. It is prospective to become as a dermal substitute in repairing
      wounds.

PMID- 22967976
TI  - [Influence of histatin 1 on the proliferation and migration of HaCaT cells].
AB  - OBJECTIVE: To study the influence of histatin 1 (Hst1) on the proliferation and
      migration of human epidermal cell line HaCaT. METHODS: (1) HaCaT cells were
      routinely cultured and divided into control group, 100, 30, and 3 ug/mL Hst1
      groups, 10 ng/mL recombinant human epidermal growth factor (rhEGF) group, and 30
      ug/mL Hst1 + 10 ng/mL rhEGF group, according to the random number table (the same
      dividing method used for following grouping), with 27 samples in each group. NO
      stimulating factor was added in control group, while Hst1 and(or) rhEGF in
      corresponding concentration(s) was (were) added in the latter 5 groups. Cell
      proliferation was assayed by cell counting method at post culture hour (PCH) 24,
      48, and 72. (2) HaCaT cells were divided into control group and 100, 30, and 3
      ug/mL Hst1 groups, with 27 samples in each group. NO stimulating factor was added
      in control group, while Hst1 in corresponding concentration was added in the
      latter 3 groups. Cell cycle was assayed with flow cytometry at PCH 24, 48, and
      72, and PI was calculated. (3) HaCaT cells were divided into control group, 30
      ug/mL Hst1 group, 10 ng/mL rhEGF group, 30 ug/mL Hst1 + 10 ng/mL rhEGF group, 15
      ug/mL Hst1 + 5 ng/mL rhEGF group, and 15 ug/mL Hst1 + 10 ng/mL rhEGF group, with
      10 samples in each group. NO stimulating factor was added in control group, while
      Hst1 and(or) rhEGF in corresponding concentration(s) was (were) added in the
      latter 5 groups. Cells in each group were divided into two portions: cells in one
      portion were treated by mitomycin C for 2 hours, while cells in the other portion
      were not. Scratching assay was conducted in both portions of cells. Cell
      migration was measured at post scratching hour (PSH) 0, 16, and 24, and the wound
      area healing rate was calculated. Data were processed with analysis of variance,
      and LSD- t test or Dunnett t test was applied in paired comparison among groups.
      RESULTS: (1) At PCH 24, the cell numbers in 10 ng/mL rhEGF group and 30 ug/mL
      Hst1 + 10 ng/mL rhEGF group were significantly higher than that in control group
      (with t values respectively 3.813, 5.410, P < 0.05 or P < 0.01). Except for cell
      numbers in 30 ug/mL Hst1 group and 3 ug/mL Hst1 group at PCH 48, cell numbers in
      the other groups as treated by Hst1 and (or) rhEGF were significantly higher than
      those in control group at PCH 48 and 72 (with t values from 7.754 to 24.979, P
      values all below 0.01). At PCH 72, the cell number was obviously higher in 100
      ug/mL Hst1 group [(19.21 +/- 0.59)*104] than in 30 ug/mL Hst1 group [(16.19 +/-
      0.53)*104)] and 3 ug/mL Hst1 group [(15.38 +/- 0.13)*104], with t values
      respectively 11.391, 19.017, P values all below 0.01. The cell number was higher
      in 30 ug/mL Hst1 + 10 ng/mL rhEGF group than in 30 ug/mL Hst1 group, 3 ug/mL Hst1
      group, and 10 ng/mL rhEGF group (with t values from 4.579 to 34.884, P < 0.05 or
      P < 0.01). Cell numbers in all groups increased with prolongation of time. (2)
      Compared with those in control group at PCH 24 and 48, the percentage of cells in
      G0/G1 phase was decreased, the percentage of cells in S phase was increased
      (except for cell percentage of 30 ug/mL Hst1 group at PCH 24), and PI value was
      significantly increased in 100 ug/mL Hst1 group and 30 ug/mL Hst1 group (with t
      values from 4.752 to 16.104, P values all below 0.01). The PI value in 3 ug/mL
      Hst1 group was obviously higher than that in control group only at PCH 48 (t =
      4.609, P < 0.01). At PCH 72, only the PI value in 100 ug/mL Hst1 group was higher
      than that in control group (t = 8.005, P < 0.01). Compared among the groups
      treated by Hst1, the percentage of cells in G0/G1 phase showed an elevating
      trend, and the percentage of cells in S phase and the PI value showed a declining
      trend along with the decrease in Hst1 concentration at each time point. Compared
      within each group treated by Hst1, the percentage of cells in G0/G1 phase
      declined first and then elevated, while the percentage of cells in S phase and
      the PI value elevated first and then declined along with prolongation of time.
      (3) Without treatment of mitomycin C, the wound-area healing rate in 30 ug/mL
      Hst1 group (75.9 +/- 3.9)% at PSH 16 was significantly higher than those in
      control group and 10 ng/mL rhEGF group [(53.0 +/- 3.5)%, (61.7 +/- 2.5)%, with t
      values respectively 12.241, 7.598, P values all below 0.01], but lower than those
      in 30 ug/mL Hst1 + 10 ng/mL rhEGF group, 15 ug/mL Hst1 + 5 ng/mL rhEGF group, and
      15 ug/mL Hst1 + 10 ng/mL rhEGF group [(95.0 +/- 4.1)%, (97.0 +/- 3.7)%, (80.5 +/-
      5.9)%, with t values from -11.324 to -2.502, P < 0.05 or P < 0.01]. After being
      treated by mitomycin C, the wound-area healing rate in 30 ug/mL Hst1 group at PSH
      16 [(54.1 +/- 4.5)%] was higher than that in control group [(35.8 +/- 5.7)%, t =
      7.790, P < 0.01], but lower than that in the same Hst1 concentration but without
      mitomycin C treatment group (t = -10.863, P < 0.01). There was no statistically
      significant difference in the wound-area healing rate between 30 ug/mL Hst1 group
      and other groups treated by Hst1 and rhEGF at PSH 16 (with t values from 0.061 to
      2.030, P values all above 0.05). Compared within each group with or without
      treatment of mitomycin C, the wound-area healing rate at PSH 16 was not
      significantly different from that at PSH 24 (with F values from 0.856 to 3.062, P
      values all above 0.05). CONCLUSIONS: Hst1 can promote the proliferation and
      migration of HaCaT cells. It has synergic effect with rhEGF on the promotion of
      cell proliferation, but their synergic effect on cell migration is not obvious.

PMID- 22967977
TI  - [Effects of P 311 on the migration of epidermal stem cells in mice with
      superficial partial-thickness burn and injured cell model in vitro].
AB  - OBJECTIVE: To study effects of P311 on the migration of epidermal stem cells
      (ESCs) in mice with superficial partial-thickness burn and injured cell model in
      vitro and to explore the mechanism. METHODS: (1) Eighteen male C(57) BL/6 mice
      were used. Fifteen of them were inflicted with superficial partial-thickness burn
      on the back. In three injured mice wound tissue and skin of wound edge were
      obtained at post burn hour (PBH) 6, 12, 24, 48, 72 respectively. The rest three
      mice were used as normal control, and samples were harvested with the same method
      as above. The expressions of P311 in harvested samples were assessed with biotin
      streptavidin-peroxidase (SP) staining. (2) Six newly born C(57) BL/6 mice were
      intraperitoneally injected with 50 ug/g BrdU (two times a day) for three days for
      ESCs-labelling. Seven weeks later, the mice were inflicted with superficial
      partial-thickness burn on the back. Serial slices of burn wound tissue were
      prepared at PBH 72 and immunohistochemically stained with SP for observation of
      the co-localization of BrdU-positive ESCs and P311-positive cells. (3) The empty
      vector pAdEasy-enhanced green fluorescence protein (EGFP) and the adenovirus P311
      expressing vector named pAdEasy-EGFP-P311 were constructed and packed. Human ESCs
      were isolated by the method of rapid adhesion to collagen IV. After being divided
      into P311 high-expressing group (n = 3) and EGFP control group (n = 3), the ESCs
      in two groups were respectively infected by pAdEasy-EGFP-P311 and pAdEasy-EGFP.
      Scratching assay was performed on ESCs in both groups after they were treated by
      mitomycin C for 2 hours. The remaining area within the fixed range was measured
      at post scratching hour (PSH) 0, 24, 48, and 72, and the wound-area healing rate
      was calculated. Data were processed with independent samples t test. RESULTS: (1)
      Expression amount of P311 was different in different parts of wound at different
      time points after burn. Expression amount of P311 in the newly formed epidermis
      and hair follicle of wound increased along with prolongation of time. Expression
      amount of P311 in the epidermis and hair follicle of wound edge peaked at PBH 12
      and then decreased to normal levels at PBH 72. (2) Co-localization of BrdU
      positive ESCs and P311-positive cells was observed in the new epidermal layer of
      wound tissue of mice, where ESCs were labeled by BrdU. (3) At PSH 48 and 72,
      wound-area healing rate was obviously higher in P311 high-expressing group [(69
      +/- 31)%, (89 +/- 26)%] than in EGFP control group [(35 +/- 12)%, (46 +/- 31)%,
      with t values respectively -2.336, -2.611, P values all below 0.05]. CONCLUSIONS:
      P311 may promote the migration of ESCs both in rats with superficial partial
      thickness burns and in injured cell model in vitro, and it may play an important
      role in wound healing.

PMID- 22967978
TI  - Reconstruction of the 1918 influenza virus: unexpected rewards from the past.
AB  - The influenza pandemic of 1918-1919 killed approximately 50 million people. The
      unusually severe morbidity and mortality associated with the pandemic spurred
      physicians and scientists to isolate the etiologic agent, but the virus was not
      isolated in 1918. In 1996, it became possible to recover and sequence highly
      degraded fragments of influenza viral RNA retained in preserved tissues from
      several 1918 victims. These viral RNA sequences eventually permitted
      reconstruction of the complete 1918 virus, which has yielded, almost a century
      after the deaths of its victims, novel insights into influenza virus biology and
      pathogenesis and has provided important information about how to prevent and
      control future pandemics.

PMID- 22967979
TI  - "Listening in" on how a bacterium takes over the plant vascular system.
AB  - Bacteria that infect the plant vascular system are among the most destructive
      kind of plant pathogens because pathogen proliferation in the vascular system
      will sooner or later shut down the plant's water and nutrient supply and
      necessarily lead to wilting and, in the worst case, death of the entire plant.
      How bacterial plant pathogens adapted to life in the plant vascular system is
      still poorly understood. As described in a recent article, Caitilyn Allen and her
      group studied the archetypical vascular pathogen Ralstonia solanacearum, the
      causative agent of bacterial wilt disease in almost 200 crop and ornamental plant
      species, and they have described the results of a microarray analysis that
      allowed them to "listen in" on the pathogen's sabotaging activity inside the
      plant [J. M. Jacobs et al., mBio 3(4):e00114-12, 2012]. Besides gaining for the
      first time an almost complete picture of R. solanacearum gene expression during
      infection, this approach allowed revision of a wrong assumption about the
      activity of the pathogen's type III secretion system during infection and
      uncovered the importance of sucrose as an energy source for vascular pathogens
      like R. solanacearum.

PMID- 22967980
TI  - Genetic control of translesion synthesis on leading and lagging DNA strands in
      plasmids derived from Epstein-Barr virus in human cells.
AB  - DNA lesions in the template strand block synthesis by replicative DNA polymerases
      (Pols). Eukaryotic cells possess a number of specialized translesion synthesis
      (TLS) Pols with the ability to replicate through DNA lesions. The Epstein-Barr
      virus (EBV), a member of the herpesvirus family, infects human B cells and is
      maintained there as an extrachromosomal replicon, replicating once per cycle
      during S phase. Except for the requirement of the virus-encoded origin-binding
      protein EBNA1, replication of plasmids containing the EBV origin of replication
      (oriP) is controlled by the same cellular processes that govern chromosomal
      replication. Since replication of EBV plasmid closely mimics that of human
      chromosomal DNA, in this study we examined the genetic control of TLS in a duplex
      plasmid in which bidirectional replication initiates from an EBV oriP origin and
      a UV-induced cis-syn TT dimer is placed on the leading- or the lagging-strand DNA
      template. Here we show that TLS occurs equally frequently on both the DNA strands
      of EBV plasmid and that the requirements of TLS Pols are the same regardless of
      which DNA strand carries the lesion. We discuss the implications of these
      observations for TLS mechanisms that operate on the two DNA strands during
      chromosomal replication and conclude that the same genetic mechanisms govern TLS
      during the replication of the leading and the lagging DNA strands in human cells.
      IMPORTANCE: Since replication of EBV (Epstein-Barr virus) origin-based plasmids
      appropriates the cellular machinery for all the steps of replication, our
      observations that the same genetic mechanisms govern translesion synthesis (TLS)
      on the two DNA strands of EBV plasmids imply that the requirements of TLS Pols
      are not affected by any of the differences in the replicative Pols or in other
      proteins that may be used for the replication of the two DNA strands in human
      cells. These findings also have important implications for evaluating the
      significance of results of TLS studies with the SV40 origin-based plasmids that
      we have reported previously, in which we showed that TLS occurs similarly on the
      two DNA strands. Since the genetic control of TLS in SV40 plasmids resembles that
      in EBV plasmids, we conclude that TLS studies with the SV40 plasmids are as
      informative of TLS mechanisms that operate during cellular replication as those
      with the EBV plasmids.

PMID- 22967981
TI  - Repression by cyclic AMP receptor protein at a distance.
AB  - In a previous study of promoters dependent on the Escherichia coli cyclic AMP
      receptor protein (CRP), carrying tandem DNA sites for CRP, we found that the
      upstream-bound CRP could either enhance or repress transcription, depending on
      its location. Here, we have analyzed the interactions between CRP and the C
      terminal domains of the RNA polymerase alpha subunits at some of these promoters.
      We report that the upstream-bound CRP interacts with these domains irrespective
      of whether it up- or downregulates promoter activity. Hence, disruption of this
      interaction can lead to either down- or upregulation, depending on its location.
      IMPORTANCE: Many bacterial promoters carry multiple DNA sites for transcription
      factors. While most factors that downregulate promoter activity bind to targets
      that overlap or are downstream of the transcription start and -10 element, very
      few cases of repression from upstream locations have been reported. Since more
      Escherichia coli promoters are regulated by cyclic AMP receptor protein (CRP)
      than by any other transcription factor, and since multiple DNA sites for CRP are
      commonplace at promoters, our results suggest that promoter downregulation by
      transcription factors may be more prevalent than hitherto thought, and this will
      have implications for the annotation of promoters from new bacterial genome
      sequences.

PMID- 22967982
TI  - Management of massive and submassive pulmonary embolism.
AB  - Massive pulmonary embolism has a high mortality rate despite advances in
      diagnosis and therapy. This article attempts to review the evidence-based risk
      stratification, diagnosis, initial stabilization, and management of massive and
      submassive pulmonary embolism. 

PMID- 22967983
TI  - HDL cholesterol: all hope is not lost after the torcetrapib setback--emerging
      therapeutic strategies on the horizon.
AB  - Lowering low-density lipoprotein cholesterol (LDL) has been definitely shown to
      reduce cardiovascular events and improve clinical outcomes in the literature. As
      a result, LDL lowering has become the cornerstone of therapeutic approaches to
      cardiovascular disease prevention. Recently, there has been a focus on targeting
      other lipid fractions to improve the clinical risk profile of patients. Raising
      high-density lipoprotein (HDL) has received considerable attention. Low HDL
      levels are often seen in combination with elevated triglyceride levels. New
      therapeutic modalities are being developed to increase HDL levels. Recent failure
      of agents such as cholesteryl ester transferase protein inhibitor torcetrapib has
      highlighted the importance of measuring functionality of HDL particles and not
      just focus quantitatively on HDL-C levels. The heterogeneity of HDL within the
      systemic circulation results from constant remodeling of particles in response to
      several factors. Established dyslipidemia therapies such as stains, fibrates, and
      niacin have already been well known in the literature to have a substantial
      benefit. Lifestyle changes such as smoking cessation and moderate alcohol
      consumption have also shown to have some benefit. Several novel HDL therapies are
      currently being developed, but only the cholesteryl ester transferase protein
      inhibitors have received considerable attention. Although torcetrapib has
      received some negative attention due to adverse effects, this overall class of
      therapeutic agents still holds a lot of promise. Newer agents without the
      concerned toxicities are currently being developed. ApoA-1-related peptides,
      peroxisome proliferator-activated receptor agonists, endothelial lipase
      inhibitors, and liver X receptor agonists are some of the other novel agents
      currently in various stages of development. 

PMID- 22967984
TI  - Effects of anthocyanins on active avoidance test of rats exposed to disruption of
      diurnal rhythm.
AB  - The present study was undertaken to assess the effects of the natural antioxidant
      anthocyanins on learning and memory of rats in experimental model of oxidative
      stress. Our preliminary experiments demonstrated that disruption of diurnal
      rhythm via exposition of rats to constant light for 14 days caused excessive
      generation of free radicals in their brains. It is known that free radicals
      impair cognitive functions. This study investigated the effects of anthocyanins
      on cognitive functions of rats in a shuttle-box active avoidance test. In the
      shuttle-box, stressed rats showed significantly increased latency time and
      decreased number of avoidances and escapes in the learning sessions. Rats treated
      with anthocyanins had increased number of avoidances and escapes and
      significantly decreased latency time during the learning sessions. Our results
      demonstrated that this model of oxidative stress impaired learning and memory of
      experimental rats. Moreover, chronic administration of anthocyanins (200 mg/kg
      orally) improved brain functions of the rats. Our data suggest that anthocyanins
      have a protective role on rat brain and improve cognitive functions in this model
      of oxidative stress.

PMID- 22967985
TI  - A mechanistic derivation of the DeAngelis-Beddington functional response.
AB  - We give a derivation of the DeAngelis-Beddington functional response in terms of
      mechanisms at the individual level, and for the first time involving prey refuges
      instead of the usual interference between predators.

PMID- 22967986
TI  - Effectiveness of cyclooxygenase-2 inhibition in limiting abdominal aortic
      aneurysm progression in mice correlates with a differentiated smooth muscle cell
      phenotype.
AB  - Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress
      over years to produce a weakened aorta with increased susceptibility for rupture,
      and currently, there are no pharmacological treatments available to slow disease
      progression. AAA development has been characterized by increased expression of
      cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation
      reduces AAA incidence in a mouse model of the disease. The current study
      determined the effectiveness of COX-2 inhibition on AAA progression when
      treatment was begun after initiation of the disease. COX-2 inhibitor treatment
      with celecoxib was initiated after angiotensin II-induced AAA formation in a
      strain of nonhyperlipidemic mice that we have previously identified as highly
      susceptible to AAA development. When analyzed at different time points during
      progression of the disease, celecoxib treatment significantly reduced the
      incidence and severity of AAAs. The celecoxib treatment also protected the mice
      from aortic rupture and death. The aneurysmal lesion displayed an altered smooth
      muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with
      increased expression of differentiated SMC markers and reduced dedifferentiation
      marker expression during AAA progression. Maintenance of a differentiated SMC
      phenotype is associated with the effectiveness of COX-2 inhibition for limiting
      AAA progression in nonhyperlipidemic mice.

PMID- 22967987
TI  - Vascular oxidative stress induced by diesel exhaust microparticles:  synergism
      with hypertension.
AB  - BACKGROUND: Epidemiological and clinical studies have shown that traffic-related
      air pollution and, particularly, diesel exhaust particles (DEP) are strongly
      linked to cardiovascular mortality. METHODS: Vascular toxicity was studied by
      assessing vasomotor responses of aortas isolated from normotensive Wistar rats
      exposed in vitro to DEP (DEP suspension and aqueous DEP extract). In vivo
      experiments were performed on Wistar rats and spontaneously hypertensive rats
      (SHRs) exposed for 4 weeks via intratracheal instillation to either DEP or saline
      vehicle. After killing, vascular responses to acetylcholine (ACh) or sodium
      nitroprusside were assessed in vitro and the expression of p22phox, a major
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit, was studied
      by real-time quantitative polymerase chain reaction. RESULTS: In aortas from
      Wistar rats, in vitro DEP incubation (both preparations) markedly inhibited the
      relaxations to ACh and slightly to sodium nitroprusside; this effect was reversed
      in the presence of superoxide dismutase. In contrast, in aortas from in vivo
      exposed animals, ACh-induced relaxations were only significantly impaired in the
      SHR group, accompanied with a significant upregulation of p22phox and no change
      in systolic blood pressure. CONCLUSIONS: Although in vitro exposure to DEP
      produces a vascular oxidative stress, repeated in vivo exposures to DEP only
      impair vascular function in SHR, via an upregulation of p22phox. This suggests a
      synergistic effect on endothelial dysfunction between particulate air pollution
      and hypertension.

PMID- 22967988
TI  - Xanthine oxidase contributes to mitochondrial ROS generation in an experimental
      model of cocaine-induced diastolic dysfunction.
AB  - Recent studies have shown that long-term cocaine use induces diastolic impairment
      and a myocardial oxidative stress. Recently, we have reported that cocaine
      induced cardiac dysfunction may be due to a mitochondrial reactive oxygen species
      (ROS) overproduction, which occurs at the same time as xanthine oxidase (XO)
      activation. In this work, we hypothesized that XO activation contributes to
      mitochondrial ROS overproduction, which in turn contributes to diastolic
      dysfunction. To test this, we used a well-established in vivo model of cocaine
      induced diastolic dysfunction. In this experimental model treated with or without
      allopurinol, an inhibitor of XO, we measured mitochondrial ROS production and
      function. Mitochondrial alterations were characterized by an increase in oxygen
      consumption through complexes I and III, a reduction in ATP production, and an
      increased ROS production specifically in isolated interfibrillar mitochondria.
      Allopurinol treatment prevented the rise in mitochondrial ROS levels and the
      decrease in ATP production. In the same way, allopurinol treatment improved
      ventricular relaxation with a decrease in Tau, an index of left ventricle
      relaxation and of end-diastolic pressure volume relation. These results confirmed
      the critical role of XO in the sequence of events leading to cocaine-induced
      cardiac dysfunction.

PMID- 22967989
TI  - Vascular remodeling-associated hypertension leads to left ventricular hypertrophy
      and contractile dysfunction in profilin-1 transgenic mice.
AB  - Hypertension is a major health problem and a main risk factor for cardiovascular
      diseases. We have shown that overexpression of profilin-1 in blood vessels of
      transgenic mice generates mechanical tone and led to vascular
      remodeling/hypertension. However, little is known whether cardiac contractile
      performance in these mice is compromised. We investigated the in vivo contractile
      function and in vitro contractile performance using isolated papillary muscles
      from both right ventricle and left ventricle of profilin-1 mice at older age. Our
      results showed mild left ventricular hypertrophy and moderate systolic
      dysfunction in profilin-1 mice as evident by increased heart/body weight ratio
      and echocardiography analysis. Under near physiological conditions, right
      ventricle papillary muscles of profilin-1 mice maintained their peak isometric
      active developed tension, and the rate of force development over the entire
      frequency range of 4-14 Hz. Positive inotropic responses to increasing Ca and
      beta-adrenergic stimulation were also maintained. Conversely, left ventricular
      papillary muscles of profilin-1 mice exhibited depressed peak isometric, peak
      isometric active developed tension and rate of force development, and depressed
      positive inotropic responses to increasing Ca and beta-adrenergic stimulation. We
      here provide functional evidence that a significant contractile dysfunction in
      profilin-1 mice exists. Targeting vascular profilin-1 signaling could represent a
      promising therapeutic approach in hypertensive patients.

PMID- 22967990
TI  - Double-dissociation of D1 and opioid receptor antagonism effects on the
      acquisition of sucrose-conditioned flavor preferences in BALB/c and SWR mice.
AB  - Sugar appetite is influenced by unlearned attractions to sweet taste and learned
      responses to sugars' taste and post-ingestive actions. In rats, sugar-conditioned
      flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not
      by opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c
      and SWR inbred mice that differ in their suppressive effects of SCH and NTX on
      sucrose intake. The present study examined whether SCH and NTX altered expression
      of previously learned sucrose-CFP and acquisition (learning) of sucrose-CFP in
      these strains. In Experiment 1, food-restricted mice were trained (10 one-bottle
      sessions) to drink a more-preferred flavored (e.g., cherry) 16% sucrose solution
      (CS+/Sucrose) on odd-numbered days, and a less-preferred flavored (e.g., grape)
      0.05% saccharin solution (CS-/Saccharin) on even-numbered days. Two-bottle tests
      with the flavors mixed in 0.2% saccharin occurred 30 min following vehicle (Veh),
      SCH (50-800 nmol/kg) or NTX (1-5mg/kg) assessing preference expression. CS+
      preference expression in BALB/c and SWR mice following Veh were significantly
      reduced by SCH and NTX. In Experiment 2, separate groups of BALB/c and SWR mice
      received Veh, SCH (50 nmol/kg) or NTX (1mg/kg) injections 30 min prior to daily
      one-bottle training sessions with the CS+/Sucrose and CS-/Saccharin solutions
      assessing preference acquisition. Subsequent two-bottle tests with the CS+ vs. CS
      solutions were conducted without injections. CS+/Sucrose training intakes were
      reduced by SCH in both strains and by NTX in BALB/c mice. In the initial two
      bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%),
      but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In
      contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but
      not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid
      receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice
      with significant strain differences observed.

PMID- 22967991
TI  - A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based
      on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome.
AB  - BACKGROUND: Aggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing
      features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL)
      (intermediate BL/DLBCL) but deviating with respect to one or more characteristics
      are increasingly recognized. The limited knowledge about these biologically
      heterogeneous lymphomas hampers their assignment to a known entity, raising
      incertitude about optimal treatment approaches. We therefore searched for
      discriminative, prognostic, and predictive factors for their better
      characterization. PATIENTS AND METHODS: We analyzed 242 cytogenetically defined
      aggressive mature BCL for differential protein expression. Marker selection was
      based on recent gene-expression profile studies. Predictive models for diagnosis
      were established and validated by a different set of lymphomas. RESULTS: CSE1L-
      and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the
      diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL
      (P<0.001 for all markers). All three markers were associated with patient outcome
      in DLBCL. A new algorithm discriminating BL from DLBCL emerged, including the
      expression of CSE1L, STAT3, and MYC translocation. This 'new classifier' enabled
      the identification of patients with intermediate BL/DLBCL who benefited from
      intensive chemotherapy regimens. CONCLUSION: The proposed algorithm, which is
      based on markers with reliable staining properties for routine diagnostics,
      represents a novel valid tool in separating BL from DLBCL. Most interestingly, it
      allows segregating intermediate BL/DLBCL into groups with different treatment
      requirements.

PMID- 22967992
TI  - ADAM-17: a novel therapeutic target for triple negative breast cancer.
AB  - BACKGROUND: Validated targeted therapy is currently unavailable for patients with
      invasive breast cancer negative for oestrogen receptors, progesterone receptors
      and HER2 [i.e., those with triple-negative (TN) disease]. ADAM-17 is a protease
      involved in the activations of several ligands that bind to and promotes
      intracellular signalling from the EGFR/HER family of receptors. PATIENTS AND
      METHODS: Expression of ADAM-17 was measured in 86 triple-negative and 96 non
      triple-negative breast cancers. The ADAM-17 specific inhibitor, PF-5480090 (TMI
      002, Pfizer) was tested in a panel of breast cancer cell lines for effects on
      functional outputs. RESULTS: In this study we show using both Western blotting
      and immunohistochemistry that ADAM-17 is expressed at significantly higher levels
      in TN than non-TN breast cancers. Using a panel of breast cancer cell lines in
      culture, PF-5480090 was found to decrease release of the EGFR ligand, TGF-alpha,
      decrease levels of phosphorylated EGFR and block cell proliferation in a cell
      type-dependent manner. Potentially important was the finding of a significant and
      moderately strong correlation between ADAM-17 activity and extent of
      proliferation inhibition by PF-5480090 (r = 0.809; p = 0.003; n = 11).
      Pretreatment of cell lines with PF-5480090 enhanced response to several different
      cytotoxic and anti-EGFR/HER agents. CONCLUSION: It is concluded that inhibition
      of ADAM-17, especially in combination with chemotherapy or anti-EGFR/HER
      inhibitors, may be a new approach for treating breast cancer, including patients
      with TN disease.

PMID- 22967993
TI  - Dietary patterns and upper aerodigestive tract cancers: an overview and review.
AB  - BACKGROUND: The relationship between diet and cancers of the upper aerodigestive
      tract (UADT) has been investigated through dietary patterns. DESIGN: Published
      studies on the relationship between a priori and a posteriori dietary patterns
      and UADT cancers were selected through a Medline search. RESULTS: Twenty-four
      case-control studies were identified. Most of them identified a posteriori
      dietary patterns, mainly using principal component factor analysis, and a few
      used a priori dietary patterns, based on the available evidence on known effects
      of dietary habits on UADT cancers. In one study, no association was found between
      the identified patterns and UADT cancers. All the remaining 23 papers reported at
      least one favorable or unfavorable dietary pattern related to UADT cancers. The
      most consistent findings are the beneficial role of a dietary pattern based on
      fruit and vegetables or nutrients mostly contained in such foods, and the
      unfavorable role of an alcohol drinker pattern. A possible unfavorable role of
      patterns based on meats and animal products emerged as well. CONCLUSION: The
      consistency of results among populations indicates that diets rich in fruit and
      vegetables, and poor in alcohol and animal products are favorable for UADT
      cancers.

PMID- 22967994
TI  - Predictive and prognostic factors for treatment and survival in 305 patients with
      advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC
      study.
AB  - BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI
      NEC) are limited, we reviewed clinical data to identify predictive and prognostic
      markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI
      NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic
      hospitals. RESULTS: The median survival was 11 months in 252 patients given
      palliative chemotherapy and 1 month in 53 patients receiving best supportive care
      (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had
      stable disease. Ki-67<55% was by receiver operating characteristic analysis the
      best cut-off value concerning correlation to the response rate. Patients with Ki
      67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival
      than patients with Ki-67>=55% (14 versus 10 months, P<0.001). Platinum schedule
      did not affect the response rate or survival. The most important negative
      prognostic factors for survival were poor performance status (PS), primary
      colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels.
      CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy
      treatment without delay.PS, colorectal primary and elevated platelets and LDH
      levels were prognostic factors for survival. Patients with Ki-67<55% were less
      responsive to platinum-based chemotherapy, but had a longer survival. Our data
      indicate that it may not be correct to consider all GI-NEC as one single disease
      entity.

PMID- 22967995
TI  - Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of
      InterLymph case-control studies.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and
      follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over
      60 years; DLBCL is more common in men and diagnosed at older ages than FL, which
      occurs more among women. This analysis of postmenopausal women examines the
      relationship between postmenopausal hormone therapy and NHL. DESIGN: Self
      reported use of postmenopausal hormone therapy from 2094 postmenopausal women
      with NHL and 2731 without were pooled across nine case-control studies (1983
      2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and
      95% confidence intervals (CI) estimated using logistic regression were pooled
      using random-effects meta-analyses. RESULTS: Postmenopausal women who used
      hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69
      0.90). Risks were reduced when the age of starting was 50 years or older. There
      was no clear trend with number of years of use. Current users were at decreased
      risk while those stopping over 2 years before diagnosis were not. Having a
      hysterectomy or not did not affect the risk. Favourable effects were present for
      DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66
      1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to
      menopause, is associated with a decreased risk of NHL.

PMID- 22967996
TI  - Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of
      patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2
      therapy.
AB  - BACKGROUND: Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase
      inhibitor with clinical activity in patients with ErbB2/HER2-positive breast
      cancer. PATIENTS AND METHODS: Phase I of this open-label, phase I/II study
      investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240
      mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in
      patients with solid tumors. Phase II assessed the safety, clinical activity, and
      pharmacokinetics of the combination in patients with HER2-positive metastatic
      breast cancer; the primary efficacy end point was objective response (OR).
      RESULTS: In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was
      established as the MTD. In phase II, 79 patients with HER2-positive metastatic
      breast cancer were treated at the MTD. The most common treatment-related adverse
      events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients
      discontinued treatment due to diarrhea. No clinically important skin side-effects
      were observed. The OR rate in assessable phase II patients was 41% (no prior
      lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic
      interaction between neratinib and vinorelbine. CONCLUSION: Neratinib plus
      vinorelbine showed promising antitumor activity and no unexpected toxic effects
      in HER2-positive metastatic breast cancer patients. Trial registration
      ClinicalTrials.gov #NCT00706030.

PMID- 22967997
TI  - Updated overall survival results from a randomized phase III trial comparing
      gefitinib with carboplatin-paclitaxel for chemo-naive non-small cell lung cancer
      with sensitive EGFR gene mutations (NEJ002).
AB  - BACKGROUND: NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and
      paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell
      lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR)
      mutation, previously reported superiority of gefitinib over CBDCA/PTX on
      progression-free survival (PFS). Subsequent analysis was carried out mainly
      regarding overall survival (OS). MATERIALS AND METHODS: For all 228 patients in
      NEJ002, survival data were updated in December, 2010. Detailed information
      regarding subsequent chemotherapy after the protocol treatment was also assessed
      retrospectively and the impact of some key drugs on OS was evaluated. RESULTS:
      The median survival time (MST) was 27.7 months for the gefitinib group, and was
      26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who
      received platinum throughout their treatment (n=186) was not statistically
      different from that of patients who never received platinum (n=40). The MST of
      patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel
      (DOC, Taxotere; n=76) was around 3 years. CONCLUSIONS: No significant difference
      in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably
      due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the
      many benefits and the risk of missing an opportunity to use the most effective
      agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.

PMID- 22967999
TI  - Advances in neonatal care. Guest editorial.

PMID- 22967998
TI  - Placental PPARgamma regulates spatiotemporally diverse genes and a unique
      metabolic network.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is essential for placental development. For insights into its functions in the
      placenta, we screened for PPARgamma-regulated genes by integrating expression
      profiles of Pparg-null and Rxra-null placentas with those of WT and Pparg-null
      trophoblast stem cells differentiated in the presence or absence of a PPARgamma
      agonist. Intersection of these paradigms identified high-probability PPARgamma
      target genes. A few of these genes were previously reported as PPARgamma targets
      in other tissues, but most are new in the context of either PPARgamma or
      placental biology. Transcriptional profiling demonstrated a widespread role for
      the coactivator NCOA6/AIB3, but not MED1/PBP, in PPARgamma-dependent placental
      gene expression. Spatial and temporal expression analyses revealed that PPARgamma
      impacts genes in diverse trophoblast lineages and during different stages of
      differentiation. We further validated the Ldhb gene, which encodes the H isoform
      of lactate dehydrogenase, as a robust PPARgamma target in trophoblasts, and
      propose a hypothetical model that integrates it with a network of PPARgamma
      regulated genes into a novel pathway of placental fuel metabolism. These findings
      offer insights not only into the placental functions of PPARgamma, but also into
      unique, previously unsuspected biosynthetic functions of trophoblasts.

PMID- 22968000
TI  - Application of the M Technique in hospitalized very preterm infants: a
      feasibility study.
AB  - PURPOSE: To explore the application of a novel relaxation method (the M
      Technique) in hospitalized very preterm infants in a level IIIC neonatal
      intensive care unit. DESIGN: A feasibility, observational intervention study.
      SUBJECTS: Ten very preterm infants were enrolled to receive the treatment
      intervention. Eligible infants born less than 30 weeks' gestation received the
      intervention at 30 weeks' postmenstrual age. METHODS: Based on infant readiness,
      each infant received the M Technique for 5 minutes. Physiologic parameters (heart
      rate, respiratory rate, and oxygen saturations), behavioral variables (stress and
      relaxation cues), and infant behavioral state were measured 5 minutes before,
      during, and up to 10 minutes after the intervention, continuously. RESULTS:
      Descriptive analysis revealed that baseline physiologic, behavioral state, and
      behavioral cue parameters changed during and after the application of the M
      Technique. A decrease in heart rate and respiratory rate occurred during the M
      Technique (P = .006, P > .001 respectively) and a decrease in heart rate occurred
      at the end of the M Technique session (P = .02). In addition, an increase in SaO2
      occurred during and at 5 minutes following the M Technique session (P = .04, P =
      .02, respectively). State scores decreased from baseline (mean = 5.1; range, 3-9)
      to after the intervention (mean = 2.0, range 1-4). As the intervention was
      delivered, more positive than negative behavioral cues were observed throughout,
      at the end, and after the M Technique session. CONCLUSION: In this feasibility
      study, the M Technique can be delivered without adverse effects to very preterm
      infants who are 30 weeks' postmenstrual age. Additional research is needed with a
      larger, randomized design to determine short- and long-term effects specifically
      related to neurologic outcomes.

PMID- 22968002
TI  - Epigenetics and family-centered developmental care for the preterm infant.
AB  - Adverse experiences early in life have the potential to disrupt normal brain
      development and create stress response channels in preterm infants that are
      different from those observed in term infants. Animal models show that epigenetic
      modifications mediate the effects of maternal separation and environmental stress
      on susceptibility to disease and psychobehavioral problems later in life.
      Epigenetic research has the potential to lead to the identification of biological
      markers, gene expression profiles, and profile changes that occur overtime in
      response to early-life experiences. Combined with knowledge gained through the
      use of advanced technologies, epigenetic studies have the promise to refine our
      understanding about how the brain matures and functions from multiple
      perspectives including the effect of the environment on brain growth and
      maturation. Such an understanding will pave the way for care practices that will
      allow the premature brain to develop to its full capacity and will lead to the
      best possible outcomes. Neonatal epigenetic research is emerging and rapidly
      advancing. As scientists overcome biological, technical, and cost-related
      challenges, such research has a great potential in determining key environmental
      factors that affect the preterm genome, allowing for targeted interventions. The
      purpose of this article is to explore existing literature related to epigenetic
      mechanisms that potentially mediate the effects of the environment on preterm
      infant brain development.

PMID- 22968001
TI  - The effects of environmental noise and infant position on cerebral oxygenation.
AB  - PURPOSE: To assess how different infant positions and peak sound levels affected
      cerebral oxygen saturation over time. SUBJECTS: Twenty-four premature infants who
      were born less than 32 weeks' gestational age without congenital cardiac,
      neurologic, and gastrointestinal anomalies. DESIGN: Repeated-measures design with
      the first observation between 2 and 48 hours of life; once again between 49 and
      96 hours of life; on day of life 7; and every 7 days thereafter until discharge
      home, transfer to another hospital, or 40 weeks postmenstrual age, whichever came
      first. METHODS: Continuous sound levels (decibels) were obtained and 2 infant
      positions were performed while measuring cerebral oxygen saturation during 40
      minute observation periods. MAIN OUTCOME MEASURES: Effect of peak sound and
      differences in infant position on cerebral oxygen saturation. RESULTS: Peak sound
      levels 5 dB above the average ambient sound level did not significantly change
      cerebral oxygen saturation values. Differences in cerebral oxygenation were
      significantly less when infants were changed from a supine, head midline position
      to a right lateral, 15 degrees  head elevation compared with a left lateral, 0
      degrees  elevation position. CONCLUSIONS: Aspects of the current neonatal
      intensive care unit environment do not appear to affect cerebral oxygen
      saturation.

PMID- 22968003
TI  - A developmental care framework for a cardiac intensive care unit: a paradigm
      shift.
AB  - Within the past several decades, medical and surgical advancements have
      dramatically decreased mortality rates in neonates and infants with congenital
      heart disease. Although patients are surviving in greater numbers, little
      research is reported on issues related to newborn care for these at-risk infants.
      A developmental care model was introduced to the nursing staff at the Children's
      Hospital of Philadelphia, which included 5 core measures to support evidence
      based developmental care practices: (1) sleep, pain, and stress assessment; (2)
      management of daily living; (3) positioning, feeding, and skin care; (4) family
      centered care; and (5) a healing environment. The care practices were adapted to
      the specific issues of the late preterm and full-term infant who has experienced
      neonatal cardiac surgery. The purpose of this article is to review the process of
      implementing a development model of care in a cardiac intensive care unit.

PMID- 22968006
TI  - Three-year results of a multicenter prospective study of transoral incisionless
      fundoplication.
AB  - BACKGROUND: To date, there are no long-term data on the use of transoral
      incisionless fundoplication (TIF) for the treatment of chronic gastroesophageal
      reflux disease (GERD). We sought to prospectively evaluate the long-term safety
      and durability of TIF in a multi-center setting. METHODS: A longitudinal per
      protocol (PP) and a modified intention-to-treat (mITT) analysis at 1 and 3 years
      consisted of symptom evaluation using the GERD health-related quality of life
      (GERD-HRQL) questionnaire, medication use, upper gastrointestinal endoscopy, and
      pH-metry. RESULTS: Of 79 patients previously reported at 1 year, 12 were lost to
      follow-up, and 1 died from an unrelated cause. The remaining 66 patients were
      followed up and analyzed (mITT). Of 66 patients, 12 underwent revisional
      procedures, leaving 54 patients for PP analysis at a median of 3.1 years (range =
      2.9-3.6). No adverse events related to TIF were reported at 2- or 3-year follow
      up. On PP analysis, median GERD-HRQL score off proton pump inhibitors (PPIs)
      improved significantly to 4 (range 0-32) from both off (25 [13-38], P < .0001)
      and on (9 [0-22], P < .0001) PPIs. Discontinuation of daily PPIs was sustained in
      61% (mITT) and 74% (PP) of patients. Of 11 patients with pH data at 3 years (PP),
      9 (82%) remained normal. Based on mITT analysis, 9/23 (39%) remained normal at 3
      years. CONCLUSIONS: The clinical outcomes at 3 years following TIF, patient
      satisfaction, healing of erosive esophagitis, and cessation of PPI medication
      support long-term safety and durability of the TIF procedure for those with
      initial treatment success. Although complete normalization of pH studies occurred
      in a minority of patients, successful cases showed long-term durability.

PMID- 22968005
TI  - Effects of nitrous oxide sedation on resting electroencephalogram topography.
AB  - OBJECTIVE: To quantify the effects of nitrous oxide (N(2)O) gas on
      electroencephalogram (EEG) topography in healthy male participants. METHODS:
      Healthy male participants were administered 20% (n=8) or 40% (n=8) N(2)O while
      having high-density (modified 10-20) noise minimized EEG recordings. RESULTS:
      Nitrous oxide was found to produce clear reductions in resting total power,
      particularly at frontal-vertex sites. These reductions were found to principally
      reflect reductions in band-limited delta power. Following the termination of
      N(2)O inhalation, during N(2)O washout, selective increases in frontal theta
      power were observed that increased above baseline values. CONCLUSIONS: Nitrous
      oxide does not produce the classical anteriorization of slow wave activity
      typically seen during anesthetic induction. Instead N(2)O reduces frontal slow
      wave (delta) activity, which during gas washout produces a withdrawal response of
      enhanced frontal slow wave (theta) activity. SIGNIFICANCE: Attempts to
      characterize a unitary mechanism of loss of consciousness during anesthesia on
      the basis of the topographic electroencephalographic changes is challenged by the
      distinct EEG effects that N(2)O has when compared to other well known anesthetic
      agents that include propofol and sevoflurane.

PMID- 22968007
TI  - Fenton's reagent-tuned DNA-templated fluorescent silver nanoclusters as a
      versatile fluorescence probe and logic device.
AB  - A label-free strategy based on the Fenton reaction with DNA-templated silver
      nanoclusters (DNA-Ag NCs) as a probe is demonstrated for the sequential detection
      of Cu(2+), ascorbic acid (AA) and H(2)O(2). Cu(2+) causes a structural change of
      the DNA template in DNA-Ag NCs to resist the environmental quenching and emit
      stronger fluorescence. The addition of AA in the presence of Cu(2+) results in a
      further fluorescence increase of the DNA-Ag NCs. Interestingly, an even higher
      fluorescence enhancement is recorded by introducing Cu(2+) into the DNA-Ag NCs-AA
      probing system. The fluorescence turn-on probe offers detection limits of 3 nM
      for Cu(2+) and 7 nM for AA. Thereafter, the addition of H(2)O(2) generates
      hydroxyl radicals from the Fenton reaction, which induces cleavage of the DNA
      template, leading to fluorescence quenching of the DNA-Ag NCs. This facilitates
      H(2)O(2) detection. Moreover, based on the DNA-templated fluorescent silver
      nanoclusters and Fenton reaction, a multiple logic gate system, including AND and
      a three-input logic gate, is constructed, with Cu(2+), AA and H(2)O(2) as inputs,
      and the fluorescence intensity of the DNA-Ag NCs probe as output.

PMID- 22968008
TI  - [Prevalence rates and risk factors on stroke among 50 - 79 years-olds in Beijing,
      2011].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of stroke among
      population aged 50 - 79 in Beijing, 2011. METHODS: 38 532 subjects were randomly
      selected with cluster sampling method, under the proportion to the population
      size (PPS). Each participant was invited to receive face to face standardized
      questionnaire interview, physical examination and neck ultrasonography. RESULTS:
      The standardized prevalence of stroke was 9.3%, with 11.5% and 8.1% for males and
      females respectively. The prevalence rate increased with age and was higher in
      males, in suburb areas and people with poor education. Ischemic stroke accounted
      for 80.8% of all the stroke cases, with 16.6% of the patients had one recur. The
      standardized prevalence rates of hypertension, dyslipidemia, obesity, diabetes
      mellitus were 80.7%, 29.6%, 22.9%, 16.9%, respectively. The prevalence rates of
      hypertension, dyslipidemia, obesity, diabetes mellitus, migraine, heart disease,
      carotid stenosis, sleep apnea, peripheral cascular disease, ischemic eye disease,
      high homocysteine level (HHE) and sickle cell anemia among stroke patients were
      89.3%, 39.7%, 25.4%, 25.4%, 21.4%, 23.7%, 13.2%, 6.4%, 6.5%, 5.9%, 0.3%, 0.3%,
      respectively, all higher than those without the disease. 47.9 percent of the
      stroke patients had 3 or more chronic diseases with more risk factors.
      CONCLUSION: People who were 50 to 79 years old and living in Beijing had both
      higher prevalence and recurrence rate of stroke, with the main type as ischemic
      stroke. Compared with urban area, the situation in suburb was more serious.
      Stroke patients had more risk factors. The top four relevant chronic diseases of
      stroke patients were hypertension, dyslipidemia, obesity and diabetes mellitus.
      In order to reduce or delay the occurrence or recurrence of stroke, lifestyle
      intervention programs should be adopted to control related chronic diseases at
      their early stages.

PMID- 22968009
TI  - [Association between glucose level and carotid plaque among 50 - 79 year olds
      from the communities].
AB  - OBJECTIVE: To investigate the association between fasting blood glucose levels
      and the prevalence of carotid plaque in a community-based population of Beijing
      and to further explore the association between fasting glucose levels concomitant
      wand other cardiovascular risk factors as well as the prevalence of carotid
      plaque. METHODS: This study was a part of the Chinese Multi-provincial Cohort
      Study conducted in the communities of Beijing University in 2007. All the members
      aged 50 - 79 years from the community were recruited, with 1046 of them qualified
      as without missing data. Case of diabetes was defined if the fasting glucose
      level was greater than 7.0 mmol/L or on anti-diabetic drugs. RESULTS: The mean
      level of fasting glucose was 5.89 mmol/L, and the prevalence of carotid plaque
      was 56.3%. For the reference on normal levels of fasting glucose, the risk on
      carotid plaque had an increase along with the increase of fasting glucose levels
      only under the univariate and multivariate analyses, after adjusting for age.
      However, the risk on carotid plaque in women was increased when there was an
      increase on the levels of fasting glucose. Specifically, for the reference on
      normal levels of fasting glucose, after adjusting for other cardiovascular risk
      factors, the odds of developing a carotid plaque was more than two folds in
      diabetic women. When combining the groups of risk factors (normal and abnormal)
      among the three groups of fasting glucose and assigning the normal level of risk
      factors concomitant with normal fasting glucose as a reference for both genders,
      the risk of developing a carotid plaque in diabetic women with abnormal level of
      risk factors ranked the highest, with statistical significance. When the diabetic
      patients combined with a decreased levels of HDL but increased levels of LDL,
      blood pressure, waist circumference, there appeared 2.8-(P = 0.014), 2.7-(P =
      0.010), 2.4-(P = 0.013) and 2.1-times (P = 0.031) higher risks of developing
      carotid plaque than those in the reference group, respectively. CONCLUSION: In
      this study, the prevalence of carotid plaque driven by increased fasting glucose
      was different on gender but the difference was only statistically significant in
      women. There also appeared a joint association of fasting glucose combined with
      other cardiovascular risk factors on the risk of developing a carotid plaque.

PMID- 22968010
TI  - [Status of plasma folate in the third trimester of pregnant women and newborn
      babies in the northern rural areas of China].
AB  - OBJECTIVE: To study the plasma folate concentrations in the third trimester of
      pregnant women and newborn babies so as to assess the association between them.
      METHODS: Pregnant women in Yuanshi and Laoting counties in Hebei province from
      May to June in 2009 were recruited with related information collected at
      enrollment. Those pregnant women being enrolled were followed up until delivery.
      Maternal blood was collected before delivery, and cord blood was collected after
      the expulsion of the placenta. Data from 437 pairs of women and newborns were
      analyzed. Plasma folate concentration was measured by Microbiological assay, with
      maternal plasma folate concentration < 6.8 nmol/L defined as folate deficiency.
      Neonatal plasma folate concentration below 10% was defined as relative
      deficiency. Student t-test and ANOVA were used to compare the plasma folate
      concentrations between the groups and chi(2) test was used to compare the
      situation of folate deficiency. In order to assess the association between
      maternal and newborn folate levels, logistic regression analysis was used to
      estimate the odds ratio of the neonatal plasma folate relative deficiency between
      the maternal folate deficient and normal groups after adjusting factors as age,
      BMI, region, career and education. Linear regression was used to test the trend
      by quintiles of maternal plasma folate concentration. Pearson's test was used to
      test the relationship between the ratio of neonatal and maternal plasma folate
      level and the level of maternal plasma folate. RESULTS: The geometric mean of
      maternal plasma folate concentration was 8.0 (95%CI: 7.6 - 8.5) nmol/L and the
      deficiency was 29.3%, but in newborn babies, they were 24.0 (95%CI: 23.1 - 25.0)
      nmol/L and 0.9% respectively. The plasma folate level in newborn babies was 3.0
      times as high as in maternal (t = 32.519, P < 0.01) but the neonatal plasma
      folate deficiency status was higher than in maternal (chi(2) = 137.2, P < 0.01).
      When compared with the normal plasma folate level group, the risk on neonatal
      plasma folate relative deficiency in the maternal folate deficiency group was
      significantly higher after adjusted for confounders (OR = 1.96, 95%CI: 1.02 -
      3.80). The neonatal plasma folate level significantly increased along with the
      maternal plasma folate level (P(trend) < 0.05). The ratio of neonatal and
      maternal plasma folate level was significantly inversely correlated with the
      maternal folate level (r = -0.810, P < 0.001). CONCLUSION: Folate status in
      newborns was much better than in their mothers', in the northern rural areas of
      China. The maternal folate status was positively correlated with their
      offspring's. Active placental transport for folate was significantly increasing
      when the maternal plasma folate level decreased.

PMID- 22968011
TI  - [A retrospective cohort study on the natural history of AIDS caused by blood
      transfusion].
AB  - OBJECTIVE: To study the natural history of AIDS, caused by blood transfusion.
      METHODS: All HIV infections and AIDS patients were from Hebei province, including
      those infected through blood transfusion around 1995, that were identified as
      through general census of former commercial plasma donors (FCPDs). Among those
      objects being observed during the incubation period, 354 had HIV infections
      (including 142 cases infected via plasmapheresis and 212 cases caused by
      transfusion) but had not been treated by HAART before the onset of disease.
      Objects being observed during the survival period, 141 were AIDS patients
      (including 57 cases infected via plasmapheresis and 84 cases causes by
      transfusion) but had not been treated by HAART before and after the onset of
      disease. All infectors and AIDS patients were under follow-up on the progress of
      illness or death, respectively. RESULTS: By December 31, 2010, the cumulative
      incidence among HIV infections was 88.70% (314/354), with the incidence density
      as 9.14/100 person-years (314/3435.75) and the median incubation period was 113
      months. Of 142 HIV infections in the blood donation group and 212 infections in
      the blood transfusion group, the incubation periods were 112 months and 115
      months, respectively. All of the 141 patients died 34 months after the onset,
      with the death-strength as 204.70/100 person-years (141/68.88) and the period of
      survival was 4 months. Among those 57 FCPDs infections, they were all died 24
      months after the onset, with the death-strength as 250.66/100 person-years
      (57/22.74) and the survival was 3 months. The other 84 infections who were blood
      recipients, all died 34 months after the onset, with the death-strength as
      182.05/100 person-years (84/ 46.14) and the survival was 4 months. CONCLUSION:
      Through this study, we noticed that the natural history of all the AIDS patients
      was caused by blood transmission. It was important to evaluate the natural
      history of HIV epidemics among both FCPDs and blood recipients, occurred before
      and after 1995.

PMID- 22968012
TI  - [Study on the incidence of HIV and associated risk factors through a prospective
      cohort among men who have sex with men in Beijing, China].
AB  - OBJECTIVE: To investigate the dynamic change and associated risk factors of HIV
      sero-conversion rate in Beijing. METHODS: 809 sero-negative men who have sex with
      men (MSM) were recruited in the cohort from August to December in 2009. HIV sero
      antibody, medicinal examination and behavior questionnaire interview were carried
      out every six months. RESULTS: 962 MSM with overall baseline prevalence of HIV
      infection as 6.34% (61/962) together with 809 sero-negative MSM, were enrolled in
      the cohort. Of the 809 sero-negative participants, 95.1% (769/ 809), 85.5%
      (692/809) and 71.0% (574/809) of them were retained in the 6-month, 12-month and
      18-month follow-up visits, with 19, 29 and 17 of them became HIV sero-conversion
      at 6-month, 12-month, and 18-month follow-up visits and the HIV incidence rates
      appeared to be 5.47, 12.37 and 6.86 per 100 person-years respectively. The HIV
      incidence was 7.59 per 100 person-years in the 18 months follow-up visit. Factors
      including: younger than 25-years old (HR = 2.32, 95%CI: 1.39 - 3.87), having more
      than 8 MSM partners (HR = 2.50, 95%CI: 1.49 - 4.20), less than 2000Y every month
      income (HR = 1.76, 95%CI: 1.05 - 2.95), having more than 4 homosexual partners in
      the last six months (HR = 3.50, 95%CI: 2.11 - 5.81), showing phimosis and
      redundant prepuce (HR = 2.47, 95%CI: 1.50 - 4.07) as well as positive syphilis
      test (HR = 2.62, 95%CI: 1.53 - 4.49) etc., were significantly associated with HIV
      incidence. CONCLUSION: High HIV incidence was shown among MSM in Beijing and had
      spread fast in this population, calling for more favorable prevention measures to
      be taken.

PMID- 22968014
TI  - [Behavior and knowledge on physical activity among urban junior students in
      Hangzhou].
AB  - OBJECTIVE: To study the status of physical activity (PA) and sedentary behaviors
      and relevant knowledge to it among junior students. METHODS: In a cross-sectional
      study, a self-administered questionnaire was used to assess the PA, sedentary
      behaviors and relevant knowledge on 4549 eligible urban junior students. RESULTS:
      Among the 4549 junior students, only 7.50% engaged in >= 60 minutes of PA, per
      day. Those junior students spending 2 hours on weekdays, 3 hours on weekends in
      doing homework and those spending >= 30 min on weekdays, 2 hours on weekends in
      doing other sedentary activities, accounted for the highest proportion of the
      subjects respectively. The awareness rate of spending at least 60 minutes each
      day on PA to stay fit and healthy was 24.63%. Differences in gender and grade at
      school were significantly on 'understanding of health benefits regarding PA' (P <
      0.05). CONCLUSION: Urban junior students were lack of awareness and appropriate
      behavior on physical activities so the related intervention should be taken
      actively to improve the current situation among the adolescents at school.

PMID- 22968013
TI  - [Study on the infectious risk model of AIDS among men who have sex with men in
      Guangzhou].
AB  - OBJECTIVE: To develop a human immune deficiency virus (HIV) infection risk
      appraisal model suitable for men who has sex with men (MSM) in Guangzhou, and to
      provide tools for follow-up the outcomes on health education and behavior
      intervention. METHODS: A cros-sectional study was conducted in Guangzhou from
      2008 to 2010. Based on the HIV surveillance data, the main risk factors of HIV
      infection among MSM were screened by means of logistic regression. Degree on
      relative risk was transformed into risk scores by adopting the statistics models.
      Individual risk scores, group risk scores and individual infection risk in
      comparison with usual MSM groups could then be calculated according to the rate
      of exposure on those risk factors appeared in data from the surveillance
      programs. RESULTS: Risk factors related to HIV infection among MSM and the
      quantitative assessment standard (risk scores and risk scores table of population
      groups) for those factors were set up by multiple logistic regression, including
      age, location of registered residence, monthly income, major location for finding
      their sexual partners, HIV testing in the past year, age when having the first
      sexual intercourse, rate of condom use in the past six months, symptoms related
      to sexually transmitted diseases (STDs) and syphilis in particular. The average
      risk score of population was 6.06, with risk scores for HIV positive and negative
      as 3.10 and 18.08 respectively (P < 0.001). The rates of HIV infection for
      different score groups were 0.9%, 2.0%, 7.0%, 14.4% and 33.3%, respectively. The
      sensitivity and specificity on the prediction of scores were 54.4% and 75.4%
      respectively, with the accuracy rate as 74.2%. CONCLUSION: HIV infection risk
      model could be used to quantify and classify the individual's infectious status
      and related factors among MSM more directly and effectively, so as to help the
      individuals to identify their high-risk behaviors as well as lifestyles. We felt
      that it could also serve as an important tool used for personalized HIV health
      education and behavior intervention programs.

PMID- 22968015
TI  - [Study on the status of cigarette smoking in youths from three cities of China].
AB  - OBJECTIVE: To understand the smoking status and related factors in middle school
      students from Hangzhou, Taiyuan and Guiyang cites. METHODS: A cross-sectional
      survey was adopted with 11 171 students randomly selected through a stratified
      cluster sampling method. A self-administrated questionnaire survey was employed,
      which including the information of respondents' background characteristics,
      cigarette smoking, exposure to tobacco advertisement, recognition on indirect
      tobacco advertisement, exposure to second-hand smoke, related knowledge, attitude
      and perceptions towards tobacco use etc. Data was weighted by the amount of male
      and female students in junior high, senior high and vocational middle schools in
      the above said three cities and was analyzed by complex sampling analysis methods
      of SPSS 15.0. Confidence Intervals of each indicator were used to evaluate for
      difference between groups. Logistic regression was used to explore the potential
      factors associated with smoking in youths. RESULTS: The overall attempted smoking
      rate of the three cities was 26.2% (95%CI: 23.6 - 29.1), with male as 39.9% and
      female 12.5% respectively. The current smoking rate was 12.5% (95%CI: 11.1 -
      14.2) with boys as 21.9% and girls as 3.2%. The smoking rate were different among
      three kinds of schools, with vocational school was the highest (25.8%), followed
      by senior high (7.9%) and junior high (6.3%). The rate of smoking was different
      among cities, lower with better economic situation. The average age of debut was
      11.9 years old. Nearly half of the students who smoked had no intention to quit.
      Factors that associated with smoking would include: having or wishing to have
      tobacco promotion products, having friends or families who smoke, their friends'
      attitude towards smoking behavior, and misconceptions about smoking such as
      underestimate the harm of smoking and the difficulty of quitting, realizing that
      smoking was an important way for social contact, and to be seen as being matured
      etc. CONCLUSION: Boys are much more likely than girls to smoke cigarette. Smoking
      prevalence is much higher in low-income cities. Additianally, it should be
      concerned that girls has higher smoking rate than female adults. It is urgent for
      tobacco control among adolescents, especially in low-income area in China.

PMID- 22968016
TI  - [Analysis on physical and mental health and related influential factors among
      those 'left behind' adolescents in Anhui province].
AB  - OBJECTIVE: To explore the physical and mental health status on the 'left behind'
      students in Anhui province and the related influential factors. METHODS:
      Stratified cluster sampling method was used to investigate the 682 out of 3421
      students from 7 middle schools in both south and north Anhui province, using
      multidimensional sub-health questionnaire of adolescents (MSQA) and mental health
      test (MHT), for assessment of the general condition, physical and mental health
      status. RESULTS: 14.22% of the 'left behind' students were in sub-health
      condition compared to 11.28% among the normal students, and the mental sub-health
      status represented 13.64% for the former and 10.84% for the latter. In addition,
      the 'left behind' students appeared less content with their life than those of
      staying with their parents (P < 0.05). MHT scores in the subjects were positively
      correlated with the scores on MSQA and showed significant difference (P < 0.01).
      RESULTS: from the multiple linear regression analysis showed that the mental
      health condition among the left behind students was in linear regression
      relationship with the decreased physical activity (beta = 1.456, P = 0.001),
      emotional problems (beta = 1.096, P = 0.000) and problems of social adaptation
      (beta = 1.011, P = 0.006). The status of physical sub-health in the Anhui
      province showed that there was no significant difference in each of the study
      group (P > 0.05). CONCLUSION: Decreased physical activity and emotion aporia as
      well as difficult social adaptation were major factors leading to degenerated
      mental health levels in the 'left-behind' adolescents. The findings suggested
      that the mental health status could be improved in this population through better
      management on their body-health condition.

PMID- 22968017
TI  - [The current epidemic situation and surveillance regarding hemorrhagic fever with
      renal syndrome in China, 2010].
AB  - OBJECTIVE: To analyze the surveillance data on hemorrhagic fever with renal
      syndrome (HFRS) including the epidemiological characteristics and trend of the
      disease, in 2010. METHODS: Descriptive methods were conducted to analyze the
      surveillance data in 2010 which were collected from the internet-based National
      Notifiable Disease Reporting System and 40 HFRS sentinels in China. RESULTS:
      There were 9526 cases of HFRS reported in 2010 in the country with an annual
      morbidity of 0.71/10(5), which was higher than that reported in 2009. And the
      case fatality rate in 2010 was 1.24%. During the year 2010, most cases were
      reported in spring and autumn-winter season, with November as the peak month. The
      proportion of cases reported in autumn-winter season was higher than that in
      spring. The number of cases reported in males was higher than that in females
      among all the age groups, and similar pattern of mortality could be seen in most
      of the age groups. The percentage of cases over 60 years old had increased in
      recent years. Farmers were still under the highest risk. Density and the virus
      carrying rate of animal hosts, as well as the infection rate were relatively
      stable and similar to the previous findings. As to the prevailing species,
      Apodemus agrarius and Rattus norvegicus were still the most common and leading
      animal hosts. However, the dominant species in sentinel of Yunnan were Rattus
      flavipectus and Eothenomys miletus respectively, and a new hantavirus called LUXV
      was found, namely Eothenomys miletus. CONCLUSION: HFRS cases were widely
      distributed in most provinces of China, but cases mainly focus on certain areas
      and present the nature of aggregation. The risk of outbreak could not be ruled
      out for variety of factors. Population characteristics and seasonal fluctuation
      had been changing.

PMID- 22968018
TI  - [Eco-geographic landscapes of natural plague foci in China v. biological
      characteristics of major natural reservoirs of Yesinia pestis].
AB  - OBJECTIVE: To study the biological characteristics of natural reservoirs of
      Yesinia (Y.) pestis in China. METHODS: Species and genera of natural reservoirs
      of Y. pestis in China and their faunal distribution were characterized with
      modern taxonomic techniques. The ecological roles of natural reservoirs of Y.
      pestis in the natural plague foci were determined according to the animal
      ecological experiments. RESULTS: There were 86 species of natural reservoirs of
      Y. pestis including 14 major reservoirs and 72 kinds of the secondary or
      occasional reservoirs. CONCLUSION: The biological characteristics of major
      reservoirs of Y. pestis and their roles in natural plague foci were defined.

PMID- 22968019
TI  - [Study on the characteristics of temporal distribution and the epidemic trend of
      autumn-winter type scrub typhus under time series analysis].
AB  - OBJECTIVE: To explore the characteristics of temporal distribution and epidemic
      trend of autumn-winter type scrub typhus using the time series analysis. METHODS:
      Based on the data of scrub typhus collected from Shandong Diseases Reporting
      Information System from 2006 to 2011, both spectral analysis and moving average
      analysis were used to analyze the annual data of scrub typhus while scrub typhus
      incidence in 2012 - 2014 was forecasted. Seasonal decomposition analysis was
      applied to analyze the monthly data from January of 2006 to October of 2011,
      followed by Autoregressive Integrated Moving Average Model (ARIMA) which was
      constructed to forecast case number in November and December of 2011 and compared
      to the actual incidence. RESULTS: The results of spectral analysis showed that
      the prevalence of autumn-winter type scrub typhus had a feature of '3-year
      periodicity'. A long-term up-trend was confirmed by method of moving average
      analysis, with annually case numbers of 310, 337 and another number of 366
      forecasted for 2012 to 2014, respectively, with the annual increase rate as 9%
      per-year. Data from analysis of monthly data of scrub typhus showed that through
      multiple seasonal decomposition analysis, the results indicated that the
      prevalence of this disease possessed a typical autumn-winter type. The
      seasonality indexes for scrub typhus in October and November were 8.454 and
      2.230, respectively, while others were less than 1.000. The ARIMA(0,1,1)
      (0,1,0)(12) model of (1-B)(1-B(12))X(t) = (1-0.811B)u(t) that was used to
      forecast the prevalence of autumn-winter type scrub typhus and was constructed
      with the residual error of 16 lags as white noise. The Box-Jenkins test statistic
      for the model was 3.116, giving a P value of 0.999. The model fitted the data
      well. Good accordance was achieved between the observed values and the forecasted
      values of scrub typhus in November and December of 2011 which was produced by the
      ARIMA model, and all observed values were within the forecasted 95%CI.
      CONCLUSION: The prevalence of autumn-winter type scrub typhus showed a 3-year
      periodicity, with a long-term up-trend, and the case numbers of 2012 to 2014 were
      forecasted, rising on the end with an increasing rate of 9% per year, which
      occurred seasonally with October as the peak time in every year. The ARIMA(0,1,1)
      (0,1,0)(12) model seemed to be quite appropriate in predicting the autumn-winter
      type scrub typhus.

PMID- 22968020
TI  - [Study on spatial-temporal variation of infected snail in bottomland areas after
      an integrated control strategy at village level in the marshland and lake regions
      based on geographic information system].
AB  - OBJECTIVE: To evaluate the effect of an integrated control strategy and to
      quantify the spatial-temporal variation of infected snails in the bottomland
      areas after the strategy was implemented. METHODS: Based on the geographic
      database of infected snail distribution at the village level during 2004 - 2010
      in Anxiang county, Hunan province, spatial autocorrelation analysis and spatial
      scan statistics were applied to analyze the spatial-temporal characteristics on
      the distribution of infected snails. RESULTS: The number of embankments with
      infected snails in Anxiang county decreased from 23 in 2004 to 10 in 2010, while
      the rate of frame with infected snail in embankments decreased from 4.320/00 in
      2004 to 0.120/00 in 2010. The spatial distribution of infected snails was
      nonrandom, only in 2004 and 2005 with Moran's I = 0.21 (P < 0.10) and Moran's I =
      0.13 (P < 0.10) respectively. Data from the local spatial auto-correlation
      analysis showed that the number of villages with H-H types of auto-correlation
      model had been gradually decreasing. The results of SaTScan statistics appeared
      the same as from the local spatial auto-correlation analysis, showing that the
      number of areas with increased risk was decreasing. CONCLUSION: The comprehensive
      measures with emphasis on infectious source control seemed effective for
      schistosomiasis control program. The current distribution characteristics
      provided us with evidence that the resource assignment could be more reasonably
      implemented so as to control schistosomiasis in a more effective way.

PMID- 22968021
TI  - [A comprehensive surveillance on HIV among 1,237 men who have sex with men in
      thirteen cities of Yunnan].
AB  - OBJECTIVE: To understand the knowledge, risk behaviors and HIV prevalence in men
      who have sex with men (MSM) in thirteen cities. METHODS: Target samples were
      chosen using the snowball-rolling method, with transverse KABP and HIV-antibody
      testing developed for those MSM in thirteen cities of Yunnan. RESULTS: A total of
      1237 valid questionnaires and 1129 blood samples were collected. Basic knowledge
      on HIV and the rate of the response was 93.2%. 81.1% of the respondents had anal
      sex with male partners in the last six months, of them 49.7% could persistently
      using condoms in each anal sex episode. 29.0% of the respondents had sex with
      female partners in the last six months. The HIV prevalence among the studied MSM
      was 8.2% and the prevalence of syphilis among them was 3.9%. Most risky factors
      of those MSM infected by HIV would include: not persistently use condom when
      having sex and co-infection of syphilis. CONCLUSION: Both rates of HIV infection
      associated risk behaviors and HIV prevalence were high in MSM under study that
      called for more work on HIV prevention and control MSM in Yunnan.

PMID- 22968022
TI  - [A case-crossover study on the association between heat waves and daily deaths
      caused by acute myocardial infarction].
AB  - OBJECTIVE: To explore the effects of heat wave on daily deaths caused by acute
      myocardial infarction (AMI) in Beijing. METHODS: A case-crossover design was used
      to study the impact of 5 heat waves on the daily number of AMI deaths from Jan.
      1, 1999 to Jun. 30, 2000. The effect of heat wave on death in different gender or
      age groups was also compared. The 7th day before and after death occurred was
      chosen as its own bi-directional self-control. The OR value and its corresponding
      risk period was used to reflect the impact of heat wave on daily number of AMI
      deaths, lag days and duration. RESULTS: There were five heat waves during the
      study period. The first heat wave sustained 9 days and the maximum temperature
      was 38.8 degrees C with average humidity as 46.7%. The OR value for the AMI death
      was 1.437 (95%CI: 1.066 - 1.937). The second heat wave lasted 3 days, with the
      maximum temperature of 36.8 degrees C and average humidity of 61.0%. The OR value
      for the AMI death was 1.846 (95%CI: 0.671 - 5.076). The third heat wave continued
      7 days, with the maximum temperature of 41.5 degrees C with average humidity of
      58.5%. The OR value for the daily death counts caused by AMI was 2.427 (95%CI:
      1.825 - 3.229). The fourth lasted for 3 days, with the maximum temperature of
      39.6 degrees C and average humidity as 31.9%. The OR value for the AMI deaths was
      2.857 (95%CI: 1.088 - 7.506). The fifth heat wave lasted for 4 days, with the
      maximum temperature as 37.4 degrees C, and average humidity as 42.0% during this
      period. The OR value for daily death counts caused by AMI was 1.500 (95%CI: 0.632
      - 3.560). The OR value of the first heat wave for daily death counts of men and
      women caused by AMI were 1.153 (95%CI: 0.756 - 1.758) and 1.818 (95%CI: 1.185 -
      2.790) respectively. The OR value for daily death counts of under 65 age was
      1.200 (95%CI: 0.669 - 2.153), with the OR value for the older than 64 age group
      was 1.534 (95%CI: 1.083 - 2.173). The OR value for daily death counts of older
      than 64 age women was 1.818 (95%CI: 1.109 - 2.981). The OR values of the third
      heat wave for daily death counts of men and women caused by AMI were 2.392
      (95%CI: 1.649 - 3.470) and 2.514 (95%CI: 1.613 - 3.919) respectively. The OR
      value for daily death counts of under 65 age group was 2.000 (95%CI: 1.149-3.482)
      and the OR value for the older than 64 age group was 2.623 (95%CI: 1.880 -
      3.660). The OR value for daily death counts of older than 64 age group women was
      2.800 (95%CI: 1.676 - 4.678). CONCLUSION: (1) Significant increase for daily
      death counts of AMI in Beijing was noticed during the heat wave and usually
      causing hysteretic effect. The lag phase was 0 - 2 days in general. (2) The
      increase of maximum temperature was greater at the beginning day when the heat
      wave occurred in the previous day, with shorter lag time and greater risk of AMI
      death. (3) The risk of AMI death in women was greater than in men during the heat
      wave period. (4) The risk of AMI death among those older than 64 age group was
      greater than the under 65 year olds. (5) The impact of heat wave to the elderly
      female was greater.

PMID- 22968023
TI  - [Study on growth of height among students during their adolescence in Zhongshan,
      Guangdong].
AB  - OBJECTIVE: To discuss characteristics of height growth such as Peak Height
      Velocity (PHV) and Age at Peak Height Velocity (PHA) during adolescence, and to
      compare the results with other research findings. METHODS: Primary and middle
      school students' annual physical examination data of Zhongshan in 2005 - 2010 was
      used. The height velocity by age, PHV, PHA, height velocity by PHA were
      calculated. RESULTS: The average peak height velocity boys was (10.03 +/- 1.67)
      cm/yr. and that of the girls was (8.39 +/- 1.05) cm/yr. Both findings were close
      to the results from previous similar findings. The average age at which peak
      height velocity reached 12.28 +/- 1.30 years for boys and 10.78 +/- 1.04 years
      for girls, both lower than the previous findings. The correlation coefficients,
      between height level and PHA were -0.357 (P < 0.001) for boys and -0.338 (P <
      0.001) for girls. CONCLUSION: The height levels were positively related to the
      height velocity before PHA. The Zhongshan students' PHA was lower than the
      Beijing, Shanghai and Shenyang students, also lower than American and Britain
      students', but their PHVs were similar.

PMID- 22968024
TI  - [Sero-prevalence and associated risk factors on hepatitis C in Maqiao township,
      Henan province of China].
AB  - OBJECTIVE: To describe the prevalence and risk factors of hepatitis C virus (HCV)
      occurred in Henan province, at the end of 2011. METHODS: Five villages round
      Maqiao township, including 5187 residents, were selected for the study. Five
      milliliter-blood was drawn from every one of the interviewee. Clinical data
      including age, gender and anti-HCV antibody was recorded. Patients with positive
      antibodies against HCV were tested for HCV RNA. RESULTS: A total number of 5187
      people from five villages were studied, with age span from 1 to 97. The average
      age was 48 years and the sex ratio was 1:1.34. The anti-HCV result showed that
      the prevalence was 2.27%, with 1-9 age group the lowest (1.55%) and the >= 50
      year-olds the highest (4.93%). Different villages seemed to have significant
      differences on the prevalence of HCV, with the highest as 8.68% and the lowest as
      0.55%. Under risk factors analysis and distance-infection rates linear regression
      analysis, data showed that the prevalence might have correlated to the behavior
      of a certain family-run clinic. RESULTS: from multivariate analysis indicated
      that factors as intravenous dropping, intravenous injection and the use of
      surgery/endoscope were associated with the HCV infection in this village.
      CONCLUSION: Although the public health care system had been developed for more
      than ten years, iatrogenic infection was yet responsible for the infection of HCV
      patients in the rural areas of China that called for further attention paid to
      the system.

PMID- 22968025
TI  - [Study on the Fast Testing Strategy for identifying the wild poliovirus I].
AB  - OBJECTIVE: To explore the Fast Testing Sstrategy (FTS) for wild poliovirus I
      (WP1). METHODS: Epidemiological investigations were carried out on 671 students
      from WP1 epidemic areas in China. A set of real time RT-PCR assays, including
      panenterovirus testings (PE) assay, poliovirus serotypings (PS) assay and the
      assay distinguishing wild strain from vaccine strain of poliovirus I (DWV) were
      introduced into the screening program for WPV1 to replace the conventional RT
      PCR, recommended by the China National Polio Laboratory (GNPL). Additionally,
      sensitivities of all the assays were assessed by poliovirus type I to III (Sabin
      stain) and the isolated WPV1. RESULTS: (1) 33 non-poliovirus enterovirus (NPEV)
      cases were detected, with 16 polio vaccine-related cases including 5 polio I, 1
      polio II, 3 polio III, 1 polio I + II, 4 polio I + III and 2 polio I + II + III.
      Three WPV1 cases were also detected in this study and confirmed by CNPL. (2) For
      polio virus vaccine strain, sensitivities of the set of real time RT-PCR assays
      ranged from 1 to 100 times than that of the in-house RT-PCR assay. The
      sensitivities of PE and PS assays for the detection of polio II were 100 times
      than that of the RT-PCR assay and the sensitivity of DWV assay used for the
      detection of polio I were 10 times than that of the RT-PCR assay. For WPV1, the
      sensitivity of three real time RT-PCR was 10 times hight than that of the RT-PCR
      assay. CONCLUSION: The novel FTS for WPV1 suggested by this study would include
      PE, PS and DWV. It not only could greatly shorten the testing time but also more
      sensitive than the RT-PCR and suited for emergency detection for WPV1.

PMID- 22968026
TI  - [Genetic association between interleukin-10 promoter microsatellite polymorphisms
      and hepatitis B virus infection in Yi, Yao and Han ethnic populations of Guizhou
      province].
AB  - OBJECTIVE: To investigate the association between interleukin-10 (IL-10) gene
      promoter microsatellite polymorphisms and the susceptibility to hepatitis B virus
      infection in Han, Yi and Yao ethnicities in GuiZhou province. METHODS: 500
      volunteers were selected from Guizhou province. Allelic frequency of IL-10.G and
      IL-10.R loci was identified by short tandom repeat polymerase chain reaction. The
      relativity between allelic frequency and HBV infection was analyzed. RESULTS:
      Genotype data from H-W analysis on all the IL-10 polymorphisms indicated that it
      was a random distribution. Very high HBV infection rates were found in the native
      ethnic minorities of Guizhou province. The overall HBV infection rate among the
      total population was 67.00%, with the HBV infection rates of Yi nationality in
      Weining, Yi nationality in Qianxi, Yao nationality in Libo and Han nationality in
      Libo as 51.85%, 42.86%, 79.52% and 84.30%, respectively. The polymorphisms
      distribution of IL-10.G and IL-10.R were statistically different among the ethnic
      groups (P < 0.05). The polymorphisms distribution of IL-10.R had no significant
      difference between HBV infection group and non-infection group, as well as among
      HBV natural removal group and non-infected group in all the ethnic groups. The
      frequency of IL-10.G 459 bp (19CA) was significantly higher in non-infection
      group than in the infected group (P < 0.05). The frequency of IL-10.G 471 bp
      (25CA) was significantly higher in the non-infection group than in the HBV
      natural removal group (P < 0.05). The polymorphisms distribution of IL-10.G did
      not show significant difference between the HBV infection group and the HBV
      natural removal group in all the ethnic groups. We did not find any differences
      in allelic and genotypic frequencies of IL-10.G between infection group and non
      infection group in Yi nationality in Weining, and Yao nationality in Libo (P >
      0.05), as well as HBV natural removal group and non-infected group (P > 0.05).
      CONCLUSION: The polymorphisms distribution of IL-10.R and IL-10.G did not show
      significant difference in Yi, Yao and Han ethnics population living in Guizhou
      province. IL-10.G seemed to influence the susceptibility of HBV infection in Han,
      Yao and Yi ethnics population of Guizhou province.

PMID- 22968027
TI  - [Association between the methylenetetrahydrofolate reductase gene polymorphisms
      and haplotype with toxicity response of high dose methotrexate chemotherapy].
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphisms
      (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with
      high dose methotrexate (HDMTX)-induced toxicity in children with acute
      lymphoblastic leukemia (ALL). METHODS: HDMTX-treated children with ALL (1.2 to 14
      years old) were selected from inpatient and followed for a retrospective study.
      The toxicity response of HDMTX chemotherapy was evaluated using WHO common
      toxicity criteria. Sixty-one patients with therapy-related toxicity and 36
      patients without therapy-related toxicity were genotyped for 2 SNP (677C > T and
      1298A > C) of the MTHFR gene by polymerase chain reaction-restriction fragment
      length polymorphism. Frequency of haplotypes and linkage disequilibrium of MTHFR
      gene were analyzed by SHEsis program. RESULTS: The distribution of MTHFR gene
      677C > T polymorphism did not appeare different between groups with or without
      toxicity response (chi(2) = 4.609, P = 0.100), but the 1298A > C polymorphism was
      significantly different (chi(2) = 10.192, P = 0.006). Individuals who carried C
      allele (AC + CC genotype) had a decreased risk of toxicity response compared to
      AA genotype (OR = 0.245, 95%CI: 0.099 - 0.607, P = 0.002). 677C > T and 1298A > C
      polymorphisms showed strong linkage disequilibrium (D' = 0.895). The CC haplotype
      was significantly associated with decreased risk of toxicity response (OR =
      0.338, 95%CI: 0.155 - 0.738, P = 0.005), while the TA haplotype was significantly
      associated with the increased risk of toxicity response (OR = 1.907, 95%CI: 1.045
      - 3.482, P = 0.035). CONCLUSION: MTHFR gene 1298C allele and CC haplotype might
      serve as protective factors while TA haplotype as a risk factor for the
      susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.

PMID- 22968028
TI  - [Association of both peroxisome proliferator-activated receptor, gene-gene
      interactions and the body mass index].
AB  - OBJECTIVE: To investigate the association of ten single nucleotide polymorphisms
      (SNPs) in the peroxisome proliferator-activated receptor (alpha, delta, gamma)
      with obesity and the additional role of a gene-gene interaction among 10 SNPs.
      METHODS: Participants were recruited within the framework of the PMMJS
      (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu
      Province)-cohort-population-survey in the urban community of Jiangsu province,
      China. 820 subjects (513 non obese subjects, 307 obese subjects) were randomly
      selected and no individuals were related to each other. Ten SNPs (rs135539,
      rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158,
      rs3856806, rs4684847) were selected from the HapMap database, which covered
      PPARalpha, PPARdelta and PPARgamma. Logistic regression model was used to examine
      the association between ten SNPs in the PPARs and obesity. Odds ratios (OR) and
      95% confident interval (95%CI) were calculated. Interactions were explored by
      using the Generalized Multifactor Dimensionality Reduction (GMDR). RESULTS: A
      group of 820 participants (mean age was 50.05+/- 9.41) was involved. The
      frequency of the mutant alleles of rs2016520 in obese populations was less than
      that in non-obese populations (26% vs. 33%, P < 0.01). The frequency of the
      mutant alleles of rs10865710 in obese populations was more than that in non-obese
      populations (37% vs. 31%, P = 0.01). C allele carriers had a significantly lower
      obesity occurrence than TT homozygotes [OR (95%CI) = 0.63 (0.47 - 0.84)] for
      rs2016520 but no significant association was observed between other SNP and
      incident obesity. GMDR analysis showed a significant gene-gene interaction among
      rs2016520, rs9794 and rs10865170 for the three-dimension models (P = 0.0010), in
      which prediction accuracy was 0.5834 and cross-validation consistency was 9/10.
      It also showed a significant gene-gene interactions between rs2016520 and
      rs10865170 in all the two-dimensional models (P = 0.0010), in which predictive
      accuracy was 0.5746 and cross-validation consistency was 9/10. CONCLUSION: Our
      data showed that rs2016520 was associated with lower obesity risk, as well as
      interactions among rs2016520, rs9794 and rs10865170 on incident obesity.

PMID- 22968029
TI  - [Association between serum nitric oxide level and microalbuminuria: a 1:2 matched
      case-control study].
AB  - OBJECTIVE: To investigate the association between serum nitric oxide and
      microalbuminuria. METHODS: Based on a community survey in Jinchang district
      Suzhou city, a 1:2 matched case-control study was performed. A total of 208 cases
      with microalbuminuria were recruited. The controls were selected from the same
      community, with the same level of income. After matched with age, gender, waist
      circumference and fast plasma glucose, a total of 416 controls were selected.
      Values of serum nitric oxide were tested for all eligible participants. The
      association between serum nitric oxide level and microalbuminuria were analyzed
      by using the multivariate conditional logistic regression models. RESULTS: The
      mean level of serum nitric oxide was slightly lower for individuals with
      microalbuminuria (median, interquartile range: 27.75, 14.48 - 42.15 umol/L) than
      those without (28.25, 17.40 - 43.45 umol/L). However, the difference was not
      statistically significant (P = 0.316). RESULTS: from the multivariable
      conditional logistic regression model showed that serum nitric oxide level was
      not associated with microalbuminuria, after adjustment for all the confounders.
      Compared with the highest level of serum nitric oxide, the odds ratios of
      microalbuminuria for individuals in the 1(st), 2(nd)and 3(rd) quartiles were not
      significantly different, after adjustment for confounders. In pairs with
      hypertension, the odds of microalbuminuria were 85% higher for individuals with
      the lowest level of serum nitric oxide than those with the highest level (OR =
      1.85, 95%CI: 0.96 - 3.57). Additionally, in pairs without hypertension, the odds
      of microalbuminuria was just 40% higher for individuals with the lowest level of
      serum nitric oxide than those with the highest level (OR = 1.40, 95%CI: 0.58 -
      3.40). CONCLUSION: There was no significant correlation between serum nitric
      oxide and microalbuminuria in the general population in our study.

PMID- 22968030
TI  - [A cross sectional survey on the relationship between intolerance to eggs and
      body mass index in Beijing, China].
AB  - OBJECTIVE: To explore the prevalence of intolerance to eggs and its relationship
      with body mass index in Beijing, China. METHODS: A cross sectional survey which
      included 12 766 adults from health sciences center of general hospital of the
      Chinese People's Liberation Army from August, 2008 to July, 2009 was carried out.
      Data was entered computer and organized by EpiData 3.0 software for
      epidemiological analysis. Nonconditional logistic regression model was used for
      odd ratio (OR) and 95%CI calculation, and statistics analysis was carried out by
      SPSS 13.0 software. RESULTS: Positive rate of intolerance to eggs in the cohort
      was 28.5%. Grades of intolerance to eggs were associated with sex (P < 0.05).
      Positive rate of intolerance to eggs in females (36.5%) was higher than those in
      males (24.9%). Data from multiple regression analysis showed that intolerance to
      eggs was associated with sex and body mass index. Compared with males, the OR
      (95%CI) of female was 1.732 (1.590 - 1.887). Compared with normal weights, the OR
      (95%CI) of low weights was 1.443 (1.018 - 2.045). CONCLUSION: Sex and body mass
      index mignt be associated with intolerance to eggs.

PMID- 22968031
TI  - Aberrant DNA replication in cancer.
AB  - Genomic instability plays an important role in cancer susceptibility, though the
      mechanics of its development remain unclear. An often-stated hypothesis is that
      error-prone phenotypes in DNA replication or aberrations in translesion DNA
      synthesis lead to genomic instability and cancer. Mutations in core DNA
      replication proteins have been identified in human cancer, although DNA
      replication is essential for cell proliferation and most mutations eliminating
      this function are deleterious. With recent developments in this field we review
      and discuss the possible involvement of DNA replication proteins in
      carcinogenesis.

PMID- 22968032
TI  - GRP78 expression and immunohistochemical localization in the female reproductive
      tract of mice.
AB  - The 78-kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum
      chaperone, with multiple functional roles in protein processing and provision of
      cellular protection. However, the physiological role of GRP78 in embryo
      development is not clear. Localization of GRP78 and expression of its mRNA in the
      reproductive organs throughout the estrous cycle in mice were investigated by
      immunohistochemistry and real-time polymerase chain reaction, respectively.
      Whereas there was intense staining for GRP78 in the oviduct at estrus, the
      ciliated cells of isthmus had better staining than those of infundibulum and
      ampulla at all phases of the cycle. Furthermore, GRP78 was located in the uterine
      luminal and glandular epithelial cells throughout the estrous cycle, particularly
      during the estrus phase. However, levels of GRP78 mRNA in the oviduct and uterus
      varied during the cycle, with peaks at estrus. In conclusion, GRP78 expression
      varied with the phase of the murine estrous cycle; this might be related to
      gamete transport, fertilization and early development of the zygote/embryo.

PMID- 22968033
TI  - Effect of presynchronization strategy before Ovsynch on fertility at first
      service in lactating dairy cows.
AB  - The aim of this study was to evaluate the effect of presynchronization with or
      without the detection of estrus on first service pregnancy per artificial
      insemination (P/AI) and on Ovsynch outcome in lactating dairy cows. A total of
      511 cows were divided randomly but unevenly into 3 treatment groups at 44 to 50
      days in milk (DIM). Ovsynch was started at the same time (69 to 75 DIM) in all
      three groups. Cows in the Ovsynch group (CON, N = 126) received no
      presynchronization before Ovsynch, and all cows were bred by timed AI (TAI). Cows
      in the presynchronization with estrus detection (PED) and the presynchronization
      with only TAI (PTAI) groups received two doses of prostaglandin F(2alpha) (PGF)
      14 days apart, starting at 44 to 50 DIM. Ovsynch was initiated 11 days after the
      second PGF treatment. Cows in the PED group (N = 267) received AI if estrus was
      detected after either PGF injection. Cows that were not determined to be in
      estrus after PGF injection received Ovsynch and TAI. Cows in the PTAI group (N =
      118) were not inseminated to estrus, with all cows receiving TAI after Ovsynch.
      The ovulatory response to the first GnRH injection administered as part of
      Ovsynch differed (P = 0.002) among treatment groups (83.1% in PTAI, 72.6% in PED,
      and 62.7% in CON). However, the ovulatory response to the second injection of
      GnRH during Ovsynch did not differ among treatment groups. Of the 267 PED cows, a
      total of 132 (49.4%) exhibited estrus and were inseminated. The P/AI at the 31
      day pregnancy diagnosis was similar between the cows in the PED group with AI
      after estrus detection (37.9%; 50/132) and those bred with TAI (34.1%; 46/135).
      The P/AI in the CON group (46.8%; 59/126) was greater (P < 0.05) than that in the
      PED group (36.0%; 96/267). In addition, the P/AI in the CON group was greater (P
      = 0.04) than that in the PED cows receiving TAI (34.1%; 46/135) but less than
      that in the PED cows bred to estrus (37.9%; 50/132) (P = 0.16). At the 31-day
      pregnancy diagnosis, the cows in the PTAI group had greater P/AI (55.9%; 66/118)
      than both those in the PED group (P < 0.01; either estrus or TAI) and those in
      the CON group (P = 0.08). Thus, presynchronization with PGF (PTAI) increased the
      ovulatory response to Ovsynch and improved P/AI in dairy cows. Interestingly, the
      breeding of cows to estrus during presynchronization reduced fertility to the TAI
      and overall fertility, including cows bred to estrus and TAI. These results
      indicate that maximal fertility is obtained when all cows receive TAI after the
      presynchronization protocol.

PMID- 22968034
TI  - A chronologic review of mature oocyte vitrification research in cattle, pigs, and
      sheep.
AB  - Vitrification as a means of cryopreservation has become a standard approach for
      oocytes from livestock. This paradigm shift occurred primarily as a result of the
      demonstration in 1996 that bovine oocytes are extremely susceptible to chilling
      injury. Since that early work, numerous devices have been used as supports for
      oocytes during so-called "ultra-rapid cooling", and occasionally, trials
      involving the deposition of small volumes of media containing oocytes directly
      into liquid nitrogen to facilitate cooling have been reported. Results reporting
      blastocyst development exceeding 10% are common, but variability remains high,
      and a standard method for bovine oocytes remains to be established. Oocytes from
      pigs are particularly difficult to cryopreserve, even with the use of ultrarapid
      cooling approaches. Few reports have demonstrated blastocyst development
      exceeding 5%. The application of hydrostatic pressure before vitrification
      appears to impart stress tolerance to porcine oocytes, as the results of some
      treatments have shown development to blastocysts at proportions >10%. Work on
      sheep oocyte vitrification is relatively new, and a few articles have reported
      blastocyst development at 10% or more. Messenger RNA levels are reportedly
      altered in sheep oocytes as a result of vitrification, and damage to the
      cytoskeleton is common across species.

PMID- 22968035
TI  - Effect of sequence of insemination after simultaneous thawing of multiple semen
      straws on conception rate to timed AI in suckled multiparous Nelore cows.
AB  - The objective was to determine the effect of sequence of insemination after
      simultaneous thawing of multiple 0.5 mL semen straws on conception rate in
      suckled multiparous Nelore cows. The effect of this thawing procedure on in vitro
      sperm characteristics was also evaluated. All cows (N = 944) received the same
      timed AI protocol. Ten straws (0.5 mL) of frozen semen from the same batch were
      simultaneously thawed at 36  degrees C, for a minimum of 30 sec. One straw per
      cow was used for timed AI. Frozen semen from three Angus bulls was used. Timed AI
      records included sequence of insemination (first to tenth) and time of semen
      removal from thawing bath. For laboratory analyses, the same semen batches used
      in the field experiment were evaluated. Ten frozen straws from the same batch
      were thawed simultaneously in a thawing unit identical to that used in the field
      experiment. The following sperm characteristics were analyzed: sperm motility
      parameters, sperm thermal resistance, plasma and acrosomal membrane integrity,
      lipid peroxidation, chromatin structure, and sperm morphometry. Based on logistic
      regression, there were no significant effects of breeding group, body condition
      score, AI technician, and sire on conception rate, but there was an interaction
      between sire and straw group (P = 0.002). Semen from only one bull had decreased
      (P < 0.05) field fertility for the group of straws associated with the longest
      interval from thawing to AI. However, the results of the laboratory experiment
      were unable to explain the findings of the field experiment. Sperm width:length
      ratio of morphometric analysis was the single sperm characteristic with a
      significant interaction between sire and straw group (P = 0.02). It was concluded
      that sequence of insemination after simultaneous thawing of 10 semen straws can
      differently affect conception rates at timed AI, depending on the sire used.
      Nevertheless, the effects of this thawing environment on in vitro sperm
      characteristics, remain to be further investigated.

PMID- 22968039
TI  - Engineering NGF receptors to bind Grb2 directly uncovers differences in signaling
      ability between Grb2- and ShcA-binding sites.
AB  - Grb2 and ShcA are two phosphotyrosine-binding proteins that link receptor protein
      tyrosine kinases to activation of the Ras-Erk pathway. While some receptors bind
      Grb2 directly, others bind ShcA, which provides a binding site for Grb2. In order
      to compare signal transduction through a Grb2-binding site with signal
      transduction through a ShcA-binding site, we replaced the ShcA-binding site in
      the NGF receptor with a Grb2-binding site. Our results show that the Grb2- and
      ShcA-binding sites have similar abilities to activate the Ras-Erk and PI 3-kinase
      Akt pathways. In contrast, they displayed dramatic differences in their ability
      to activate DNA synthesis.

PMID- 22968036
TI  - Reduced face identity aftereffects in relatives of children with autism.
AB  - Autism is a pervasive developmental condition with complex aetiology. To aid the
      discovery of genetic mechanisms, researchers have turned towards identifying
      potential endophenotypes - subtle neurobiological or neurocognitive traits
      present in individuals with autism and their "unaffected" relatives. Previous
      research has shown that relatives of individuals with autism exhibit face
      processing atypicalities, which are similar in nature albeit of lesser degree, to
      those found in children and adults with autism. Yet very few studies have
      examined the underlying mechanisms responsible for such atypicalities. Here, we
      investigated whether atypicalities in adaptive norm-based coding of faces are
      present in relatives of children with autism, similar to those previously
      reported in children with autism. To test this possibility, we administered a
      face identity aftereffect task in which adaptation to a particular face biases
      perception towards the opposite identity, so that a previously neutral face
      (i.e., the average face) takes on the computationally opposite identity. Parents
      and siblings of individuals with autism showed smaller aftereffects compared to
      parents and siblings of typically developing children, especially so when the
      adapting stimuli were located further away from the average face. In addition,
      both groups showed stronger aftereffects for adaptors far from the average than
      for adaptors closer to the average. These results suggest that, in relatives of
      children with autism, face-coding mechanism are similar (i.e., norm-based) but
      less efficient than in relatives of typical children. This finding points towards
      the possibility that diminished adaptive mechanisms might represent a
      neurocognitive endophenotype for autism.

PMID- 22968040
TI  - Direct reprogramming of terminally differentiated B cells into erythroid lineage.
AB  - Hematopoietic progenitors have been shown to retain plasticity and switch
      lineages by appropriate stimuli. However, mature blood cells hardly showed such
      differentiation plasticity. In this paper, we tried to reprogram mature B cells
      into erythroid lineage by expressing various hematopoietic transcription factors.
      Among various factors, GATA-1, SCL together with CCAAT/enhancer binding protein
      (C/EBP) alpha turned out to be a minimal set of factors that efficiently
      reprogrammed terminally differentiated mature B cells into erythroid lineage, as
      evidenced by colony forming assays and erythroid-specific gene expressions. This
      study sets an avenue to generate autologous erythrocytes from peripheral B cells.

PMID- 22968042
TI  - Orchidopexy patterns in Austria from 1993 to 2009.
AB  - OBJECTIVE: To evaluate orchidopexy patterns in Austria. MATERIAL AND METHODS: All
      boys with cryptorchidism who underwent orchidopexy (n = 19.998) in Austria
      between 1993 and 2009 were analyzed using the database Austrian Health
      Information System at the Austrian Federal Research and Planning Institute for
      Health Care. Regression models were constructed to examine associations between
      the probability of orchidopexy before 24 months of life and the following
      parameters: year of birth, federal state of residence, character of area of
      living (rural/urban) and hospital type. RESULTS: Average age at operation dropped
      from 6 to 4.3 years (mean 5.2 years, SD 3.8 years). Total incidence of
      orchidopexy was continuously rising throughout the study period (p < 0.0001),
      with an OR of 1.007 (95% C.I.: 1.004; 1.0100) per year. The rate of operations
      between 0 and 2 years (p < 0.001) and 3-7 years (p < 0.001) increased, while the
      rate in boys older than 7 years decreased (p < 0.001). Year of birth (p < 0.0001)
      and place of residence (p < 0.0001 and p < 0.024) are significant predictors for
      having early orchidopexy. CONCLUSION: In Austria the total incidence of
      orchidopexy is significantly rising. Moreover, the incidence of orchidopexies
      performed before 24 months of life is constantly rising with significant
      geographic differences.

PMID- 22968041
TI  - Thiocyanate: a potentially useful therapeutic agent with host defense and
      antioxidant properties.
AB  - Thiocyanate (SCN) functions in host defense as part of the secreted
      lactoperoxidase (LPO) microbicidal pathway. SCN is the preferred substrate for
      LPO-driven catalytic reduction of hydrogen peroxide (H(2)O(2)) forming
      hypothiocyanous acid (HOSCN). HOSCN is selectively generated by many peroxidase
      enzymes that can utilize SCN including: eosinophil peroxidase (EPO), gastric
      peroxidase (GPO), myeloperoxidase (MPO), salivary peroxidase (SPO), and thyroid
      peroxidase (TPO). These enzymes generate HOSCN through a two-electron
      halogenation reaction. HOSCN is a potent microbicidal agent that kills or
      nullifies invading pathogens but is better tolerated by host tissue. Some
      controversy exists as to whether physiologic levels of HOSCN are non-toxic to
      host tissue, but the disagreement appears to be based on results of enzymatic
      generation (yielding moderate steady-state exposure) versus direct high level
      acute exposure in mammalian cell lines. This apparent duality is also true of
      other endogenous oxidants such as hydrogen peroxide and relates to the difference
      between physiologically relevant oxidant production versus supra-physiologic
      bolus dosing approaches. SCN has antioxidant properties that include the ability
      to protect cells against oxidizing agents such as hypochlorous acid (HOCl) and
      repair protein chloramines. SCN is an important endogenous molecule that has the
      potential to interact in complex and elegant ways with its host environment and
      foreign organisms. SCN's diverse properties as both host defense and antioxidant
      agent make it a potentially useful therapeutic.

PMID- 22968043
TI  - High-dose Ibuprofen therapy for patent ductus arteriosus in extremely preterm
      neonates: do we have a final answer?

PMID- 22968045
TI  - Security printing of covert quick response codes using upconverting nanoparticle
      inks.
AB  - Counterfeiting costs governments and private industries billions of dollars
      annually due to loss of value in currency and other printed items. This research
      involves using lanthanide doped beta-NaYF(4) nanoparticles for security printing
      applications. Inks comprised of Yb(3+)/Er(3+) and Yb(3+)/Tm(3+) doped beta
      NaYF(4) nanoparticles with oleic acid as the capping agent in toluene and methyl
      benzoate with poly(methyl methacrylate) (PMMA) as the binding agent were used to
      print quick response (QR) codes. The QR codes were made using an AutoCAD file and
      printed with Optomec direct-write aerosol jetting((r)). The printed QR codes are
      invisible under ambient lighting conditions, but are readable using a near-IR
      laser, and were successfully scanned using a smart phone. This research
      demonstrates that QR codes, which have been used primarily for information
      sharing applications, can also be used for security purposes. Higher levels of
      security were achieved by printing both green and blue upconverting inks, based
      on combinations of Er(3+)/Yb(3+) and Tm(3+)/Yb(3+), respectively, in a single QR
      code. The near-infrared (NIR)-to-visible upconversion luminescence properties of
      the two-ink QR codes were analyzed, including the influence of NIR excitation
      power density on perceived color, in term of the CIE 1931 chromaticity index. It
      was also shown that this security ink can be optimized for line width, thickness
      and stability on different substrates.

PMID- 22968046
TI  - Health benefits in 2012: moderate premium increases for employer-sponsored plans;
      young adults gained coverage under ACA.
AB  - Health care premiums rose moderately for single and family employer-sponsored
      coverage this year, the 2012 annual Kaiser Family Foundation/Health Research and
      Educational Trust (HRET) Survey of Employer Health Benefits found. Even with the
      lingering effects of the recession, cost-sharing levels remained relatively
      stable in 2012. Also remaining stable was the rate at which employers offered
      coverage, according to the survey, which was based on telephone interviews with
      2,121 public and private employers contacted from January through May 2012. The
      average annual premiums in 2012 were $5,615 for single coverage and $15,745 for
      family coverage, an increase of 3 and 4 percent, respectively, from 2011. The
      percentage of firms offering health benefits, 61 percent, was similar to last
      year's, as was the percentage of workers at offering firms who were covered by
      their firm's health benefits, 62 percent. One noteworthy change, because of a
      provision of the Affordable Care Act, is that 2.9 million young adults who would
      not otherwise have been enrolled in a parent's employer-sponsored health
      insurance were covered by that insurance in 2012.

PMID- 22968044
TI  - Semi-mechanistic population pharmacokinetic model of multivalent trastuzumab
      emtansine in patients with metastatic breast cancer.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of
      multiple molecules of the antimicrotubule agent DM1 linked to trastuzumab, a
      humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal
      antibody. Pharmacokinetics data from phase I (n = 52) and phase II (n = 111)
      studies in HER2-positive metastatic breast cancer patients show a shorter
      terminal half-life for T-DM1 than for total trastuzumab (TTmAb). In this work, we
      translated prior preclinical modeling in monkeys to develop a semi-mechanistic
      population pharmacokinetics model to characterize T-DM1 and TTmAb concentration
      profiles. A series of transit compartments with the same disposition parameters
      was used to describe the deconjugation process from higher to lower drug-to
      antibody ratios (DARs). The structure could explain the shorter terminal half
      life of T-DM1 relative to TTmab. The final model integrates prior knowledge of T
      DM1 DARs from preclinical studies and could provide a platform for understanding
      and characterizing the pharmacokinetics of other ADC systems.

PMID- 22968047
TI  - Dissociating neural correlates of meaningful emblems from meaningless gestures in
      deaf signers and hearing non-signers.
AB  - Emblems are meaningful, culturally-specific hand gestures that are analogous to
      words. In this fMRI study, we contrasted the processing of emblematic gestures
      with meaningless gestures by pre-lingually Deaf and hearing participants. Deaf
      participants, who used American Sign Language, activated bilateral auditory
      processing and associative areas in the temporal cortex to a greater extent than
      the hearing participants while processing both types of gestures relative to
      rest. The hearing non-signers activated a diverse set of regions, including those
      implicated in the mirror neuron system, such as premotor cortex (BA 6) and
      inferior parietal lobule (BA 40) for the same contrast. Further, when contrasting
      the processing of meaningful to meaningless gestures (both relative to rest), the
      Deaf participants, but not the hearing, showed greater response in the left
      angular and supramarginal gyri, regions that play important roles in linguistic
      processing. These results suggest that whereas the signers interpreted emblems to
      be comparable to words, the non-signers treated emblems as similar to pictorial
      descriptions of the world and engaged the mirror neuron system.

PMID- 22968048
TI  - Impact of maternal aging on the molecular signature of human cumulus cells.
AB  - OBJECTIVE: To investigate the impact of maternal aging on the molecular signature
      of cumulus cells. DESIGN: Experimental study. SETTING: Research laboratory.
      PATIENT(S): Patients, young fertile oocyte donors (n = 40) and infertile women of
      advanced maternal age (40-45 years; n = 48), donated, with Institutional Review
      Board consent, cumulus cells during routine infertility treatment.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proteomic and gene expression
      profiles of cumulus cells. RESULT(S): Proteomic analysis identified a total of
      1,423 cumulus cell proteins. Statistical analysis revealed 110 (7.7%) proteins to
      be differentially expressed in relation to female aging (>1.5-fold change).
      Pathway annotation revealed significant involvement in metabolism (ACAT2,
      HSD17B4, ALDH9A1, MVK, CYP11A1, and FDFT1), oxidative phosphorylation (OP;
      NDUFA1, UQCRC1, MT-ATP6, ATP5I, and MT-ATP8), and post-transcriptional mechanisms
      (KHSRP, SFPQ, DDX46, SNRPF, ADAR, NHPL1, and U2AF2) relative to advanced maternal
      age. Gene expression analysis also revealed altered profiles in cumulus cells
      from women in their early to mid-40s. CONCLUSION(S): This novel study reveals
      that the cumulus cell molecular signature, at both the gene and protein level, is
      impacted by advanced maternal aging. A compromised follicular environment is
      evident with altered energy metabolism and post-transcriptional processes.

PMID- 22968049
TI  - Klinefelter syndrome: an argument for early aggressive hormonal and fertility
      management.

PMID- 22968052
TI  - Detection rates of trichomonas vaginalis, in different age groups, using real
      time polymerase chain reaction.
AB  - OBJECTIVE: The study aimed to compare the overall detection rate of Trichomonas
      vaginalis to Chlamydia trachomatis and Neiserria gonorrhea and report detection
      rates by age groups. MATERIALS AND METHODS: Real-time polymerase chain reaction
      was used to detect the presence of T. vaginalis, C. trachomatis, and N. gonorrhea
      in cervical samples obtained from patients during gynecological examinations. A
      total of 78,428, 119,451, and 117,494 samples from women age 12 to 75 years were
      retrospectively analyzed for the presence of T. vaginalis, C. trachomatis, and N.
      gonorrhea, respectively. T. vaginalis and C. trachomatis detection rates in
      Florida, New Jersey, and Texas were calculated in different age groups. RESULTS:
      The overall detection rate was 4.3% for T. vaginalis, 3.8% for C. trachomatis,
      and 0.6% for N. gonorrhea. The overall detection rate of T. vaginalis in Florida
      was 4.7% (n = 22,504), in New Jersey was 3.6% (n = 22,249), and in Texas was 4.5%
      (n = 33,675). Calculation of infection rates with T. vaginalis revealed
      differences between selected age groups with the highest detection rates in all 3
      states found in age group 46 to 55 years (6.2%), which was higher than the
      overall detection rates in other age groups (p < .05 for all states). For C.
      trachomatis, the highest detection rate was found in age group 12 to 25 years
      (7.3%). CONCLUSIONS: The overall infection rates of T. vaginalis were higher
      compared with those of C. trachomatis and N. gonorrhea. Detection rates of T.
      vaginalis were found to be highest among women age 46 to 55 years and may be due
      to T. vaginalis infiltrating the subepithelial glands and being detected only
      during hormone-induced or antibiotic-induced changes in the vaginal flora.

PMID- 22968053
TI  - Lichen sclerosus and immunobullous disease.
AB  - We report 3 patients with long-standing lichen sclerosus who subsequently
      developed new onset erosive disease in affected sites. Repeated biopsies were
      performed which, although not diagnostic, showed some features of bullous
      pemphigoid for 1 patient and nonspecific findings for the 2 others. Direct
      immunofluorescence showed the characteristic findings of bullous pemphigoid in
      the first and pemphigus vulgaris in the others. All 3 patients were treated with
      immunosuppressive agents, and their condition improved dramatically.

PMID- 22968054
TI  - Anal intraepithelial lesions in women with human papillomavirus-related disease.
AB  - OBJECTIVE: This study aimed to determine the prevalence of anal intraepithelial
      lesions in women with histologic diagnosis of intraepithelial lesions of the
      lower genital tract. MATERIALS AND METHODS: This was a cross-sectional study
      conducted at the Lower Genital Tract and Colposcopy Unit of Hospital de Clinicas
      "Jose de San Martin," University of Buenos Aires, Argentina. A total of 481 women
      with histologically confirmed low-grade and high-grade cervical, vaginal, or
      vulvar intraepithelial lesions were evaluated between 2005 and 2011. They were
      referred for cytologic samples and examination with high-resolution anoscopy. We
      obtained biopsy specimens of any suspicious colposcopic images. RESULTS: Of a
      total of 481 patients, 404 (84%) were immunocompetent, 31 (6.4%) were HIV+, and
      46 (9.6%) had other causes of immunosuppression. Moreover, of the 481 patients,
      134 (27.86%) had anal intraepithelial neoplasia (AIN); 28 (5.82%) had high-grade
      AIN and 106 (22%) had low-grade AIN. Women with high-grade cervical
      intraepithelial neoplasia (CIN 2, 3) had 2 times the odds of developing AIN
      compared with women with low-grade CIN (CIN 1) (odds ratio = 1.91, 95% confidence
      interval = 1.1-3.6). Regarding localization, we found statistically significant
      difference between the frequency of vulvar and anal lesions. Women with vulvar
      condylomata and vulvar intraepithelial neoplasia (VIN) may be more likely to
      develop AIN. CONCLUSIONS: Immunocompetent women with CIN, vaginal intraepithelial
      neoplasia, or VIN may also present high-grade or low-grade anal intraepithelial
      lesions so we should consider AIN as part of multicentric disease of the lower
      genital tract. Cervical intraepithelial neoplasia, VIN, condyloma accuminatta,
      and vaginal intraepithelial neoplasia could be warning signs of anal
      intraepithelial lesions.

PMID- 22968055
TI  - Experience of symptoms, sexual function, and attitudes toward counseling of women
      newly diagnosed with vulvodynia.
AB  - OBJECTIVE: This study aimed to assess health beliefs and behaviors, experience of
      pain, coping mechanisms, sexual function, and attitudes toward counseling of
      patients newly diagnosed with vulvodynia. MATERIALS AND METHODS: Participants
      were enrolled from all newly diagnosed vulvodynia patients seen at the University
      of Michigan Vulvar Disease Clinic at Chelsea. Participants completed a
      questionnaire assessing perceptions and beliefs about their vulvodynia, coping
      ability, sexual function, and interest in counseling. RESULTS: Thirty-one women
      were enrolled, ranging in age from 21 to 81 years; 68% had current partners. On a
      scale of 1 to 10 (low to high), participants rated their symptoms as severe-(mean
      [SD] = 7.42 [1.50]), perceived little control over symptoms (2.61 [2.64]); were
      very concerned about symptoms (8.77 [1.73]); and were very emotionally affected
      by their disorder (7.00 [2.82]). During the previous 4 weeks, 52% reported low to
      no sexual desire; 71% reported being dissatisfied with their overall sex life;
      26% were not comfortable saying no to partner sex; 23% to 36% did not attempt
      penetration; and for 36%, their pain was rated as high or very high. Sixty-one
      percent of women indicated that they would consider counseling for coping with
      vulvar pain. In addition, 29% (9/31) said they "would" and 48% (15/31) said they
      "maybe would" consider seeing a sex therapist for their vulvar pain. CONCLUSIONS:
      Women with newly diagnosed vulvodynia report substantial impact of vulvar pain
      but feel little control over symptoms. Sexual desire and sexual satisfaction are
      low. Most of the respondents would consider counseling to help address these
      issues.

PMID- 22968056
TI  - Unprovoked vestibular burning in late estrogen-deprived menopause:  a case
      series.
AB  - OBJECTIVE: This study aimed to document cases of severe menopausal vulvar burning
      localized to the vestibule. MATERIALS AND METHODS: Seven postmenopausal women
      presented to a vulvar clinic between 2007 and 2011 complaining of debilitating
      constant vulvar burning pain. They were treated according to the vulvar findings.
      Statistical tools were descriptive. RESULTS: The women's ages ranged from 56 to
      79 years (mean age = 67 years). Pain had begun 1 to 4 years before presentation
      (mean = 1.8 years) and was vestibular. Five had contraindications to estrogen
      supplements. Only 1 patient was using estrogen; the mean number of years from
      menopause to onset of burning was 16 years (range = 4-27 years). Three patients
      developed pain during or after aromatase inhibitor therapy for breast cancer.
      Pelvic floor myalgia was present in 3 patients. Of the patients, 3 improved on
      systemic estrogen, 3 improved using topical vestibular estrogen therapy, and 1
      was managed with reassurance alone. Vestibulodynia regressed in those using
      estrogen supplementation. One patient noted resolution after localized removal of
      vestibular mucosa. CONCLUSIONS: Severe unprovoked vestibulodynia can present as
      unprovoked generalized pain in late menopause, and topical lidocaine can aid the
      diagnosis. Constant pain can arise after years of only provoked pain or in
      association with further lowering of estrogen from antiestrogen therapy for
      breast cancer. Therapy to the vestibule can provide relief. Lidocaine and local
      application of estrogen cream to the vestibule are effective therapies, and
      physical therapy can be important. With encouragement to avoid estrogen during
      menopause and with the increasing use of aromatase inhibitors for breast cancer,
      menopausal unprovoked vestibulodynia may be increasing and can be challenging to
      diagnose and treat.

PMID- 22968057
TI  - Quantification of normal vaginal constituents using a new wet preparation
      technique.
AB  - OBJECTIVE: This study aimed to evaluate a new method for preparing vaginal wet
      preparations to enable quantification of cells and lactobacilli. The current
      nonstandardized technique allows for a variable amount of vaginal fluid
      collected, diluted by a variable amount of saline/KOH, and no quantification of
      constituents. MATERIALS: The vaginal fluids from 100 randomly selected women
      without vulvovaginitis symptoms presenting to the author's practice at Mayo
      Clinic underwent analysis by the quantification technique. Women were excluded if
      they were younger than 18 years, had antibiotics within the past 2 months,
      currently on their period, had placed anything in the vagina for the past 24
      hours, used Depo-Provera, or were lactating. METHODS: All the wet preparations
      were made by mixing the natural vaginal fluids with 3 mL of sterile normal
      saline. Spinal diluting fluid was added to the saline preparation. The saline and
      KOH mixtures were injected into separate wells of KOVA Glasstic Grid Slide and
      analyzed with a phase-contrast microscope at 40* and 60*. The concentration of
      leukocytes, lactobacilli, and squamous cells and the degree of maturation of the
      majority (>50%) of squamous cells were assessed, and it was determined whether
      there was excessive non-lactobacilli bacteria (EB) as evident by clumps of
      bacteria in the background fluid and speckling on the squamous cells. RESULTS:
      The 3 most common patterns to occur were as follows: First, 51% (95% confidence
      interval [CI] = 41%-60%) of the total specimens had abundant lactobacilli, no
      leukocytes, more than 50% fully maturated squamous cells, and no EB. Second, 22%
      (95% CI = 14%-32%) of the total specimens had low lactobacilli counts, no
      leukocytes, more than 50% undermaturated squamous cells, and no EB. Third, 12%
      (95% CI = 6%-20%) of the total specimens had abundant lactobacilli, leukocytes,
      more than 50% fully maturated squamous cells, and no EB. CONCLUSIONS: It is
      imperative to be able to objectively quantify normal vaginal secretion
      constituents so that (1) the abnormal patterns can be demarcated and (2)
      treatment targets of what constitutes healthy vaginal conditions can be provided.

PMID- 22968058
TI  - Cream with cutaneous fibroblast lysate for the treatment of provoked
      vestibulodynia:  a double-blind randomized placebo-controlled crossover study.
AB  - OBJECTIVE: Is treatment of provoked localized vulvodynia with cutaneous lysate
      skin cream containing human cytokines effective? METHODS: This is a double-blind
      placebo-controlled randomized crossover trial with a study and a placebo cream
      applied twice daily for 3 months, 1-week washout, followed by a 3-month crossover
      medication in 30 patients experiencing provoked localized vulvodynia with visible
      vulvar erythema. Tolerability of the product, sexual functioning, and clinical
      findings were the main outcomes. A linear model for repeated measures was used
      for all visits. Effect after 4 weeks of treatment, effect after 12 weeks of
      treatment, and, finally, carryover effects of first and second order were
      estimated. A Wilcoxon signed rank test was used to evaluate 4- and 12-week
      changes within a group, and Mann-Whitney U test was used to evaluate 4- and 12
      week changes between groups. RESULTS: Tolerability of the cream was excellent and
      not different from that of placebo. During the first 12 weeks, use of the active
      cream resulted in a significant reduction in pain during sexual activity after 4
      and 12 weeks (p < .05); however, use of the placebo cream did not. When analyzing
      the entire pain data with the statistical model for crossover clinical study
      design, the active cream resulted in a decrease of 1.1 points (95% confidence
      interval = -0.6 to 2.8, p = .20) and 1.3 points (95% confidence interval = 0.1 to
      2.5, p = .037) in the visual analog scale score compared with that of placebo
      after 4 and 12 weeks of treatment, respectively. There was evidence for a second
      order carryover effect (p = .024). The pain reduction was most evident for women
      with secondary dyspareunia. Erythema was reduced after use of the cream at 4 (p =
      .03) and 12 (p = .01) weeks but not after placebo. CONCLUSIONS: As opposed to
      placebo, use of cutaneous lysate cream was more effective in reducing focal
      redness and pain while having intercourse in patients with provoked localized
      vulvodynia with erythema.

PMID- 22968059
TI  - Vulvar psoriasis in adults and children:  a clinical audit of 194 cases and
      review of the literature.
AB  - OBJECTIVE: There are limited data on psoriasis as it affects the vulva in the
      medical literature. This observational study aimed to describe the symptoms,
      signs, and management of vulvar psoriasis in adults and children in a private
      vulvar disease referral practice. MATERIALS AND METHODS: A review of the existing
      literature on vulvar psoriasis was used to generate inclusion criteria of a
      chronic noninfective erythematous vulvitis without vaginal involvement. Between
      January 2009 and October 2011, 201 patients presenting with these criteria were
      coded as having psoriasis in a computerized database where standardized data were
      collected. In 194 of these patients, adequate data were available to include in
      the study. RESULTS: Only 12.3% of the patients presented with psoriasis as a
      provisional diagnosis with a mean symptom duration of 4.5 years (range = 6 weeks
      to 35 years). The most common presentation was a pruritic, bilaterally
      symmetrical, erythematous, nonscaly, well-demarcated macular eruption or slightly
      raised plaque (82.5%). Of the remaining patients, 9.2% presented with only
      diffuse symptomatic erythema, whereas 8.2% were symptomatic without erythema. In
      64.9% of the patients, evidence of psoriasis was found on other parts of the
      skin. Initial induction treatment with potent topical corticosteroid followed by
      a maintenance treatment with less potent topical steroids and other psoriasis
      specific treatment such as tar creams and calcipotriol resulted in a suppression
      of disease in 93.8% of the patients during a mean follow-up duration of 8.9
      months (range = 1 month to 7.25 years). CONCLUSIONS: Vulvar psoriasis is a
      difficult diagnosis that should be considered in patients presenting with a
      chronic erythematous vulvitis without vaginitis. It is a chronic relapsing skin
      condition that requires long-term management.

PMID- 22968060
TI  - Tuning the breathing behaviour of MIL-53 by cation mixing.
AB  - A mixed cation MIL-53(Cr-Fe) MOF has been obtained by direct synthesis. Multiple
      experimental techniques have demonstrated the presence of a genuine mixed phase,
      leading to a breathing behaviour different from either of the single cation
      analogues.

PMID- 22968061
TI  - Lithium oxides precipitation in nonaqueous Li-air batteries.
AB  - Lithium-air/oxygen battery is a rising star in the field of electrochemical
      energy storage as a promising alternative to lithium ion batteries. Nevertheless,
      this alluring system is still at its infant stage, and the breakthrough of
      lithium-air batteries into the energy market is currently constrained by a
      combination of scientific and technical challenges. Targeting at the air
      electrode in nonaqueous lithium-air batteries, this review attempts to summarize
      the knowledge about the fundamentals related to lithium oxides precipitation,
      which has been one of the vital and attractive aspects of the research
      communities of science and technology.

PMID- 22968063
TI  - Update on the comparative safety of colloids:  was this review really systematic?

PMID- 22968062
TI  - Adjuvant chemotherapy with FOLFOX for primary colorectal cancer is associated
      with increased somatic gene mutations and inferior survival in patients
      undergoing hepatectomy for metachronous liver metastases.
AB  - OBJECTIVE: We hypothesized that metachronous colorectal liver metastases (CLM)
      have different biology after failure of oxaliplatin (FOLFOX) compared to 5
      fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal
      cancer (CRC). BACKGROUND: It is unclear whether patients treated with liver
      resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes
      than those who received 5-FU or no chemotherapy. METHODS: We identified 341
      patients who underwent hepatectomy for metachronous CLM (disease-free interval
      >=12 months, 1993-2010). Mass-spectroscopy genotyping for somatic gene mutations
      in CLM was performed in a subset of 129 patients. RESULTS: Adjuvant treatment for
      primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy
      in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but
      lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was
      smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy
      (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization,
      metastases number, and carcinoembryonic antigen levels were similar. Disease-free
      survival (DFS) and overall survival (OS) rates after hepatectomy were worse in
      patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45%
      (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate
      analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P <
      0.0001). Mutation analysis revealed >=1 mutations in 57% of patients (27/47)
      after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P =
      0.011). CONCLUSIONS: Adjuvant FOLFOX for primary CRC is associated with a high
      rate of somatic mutations in liver metastases and inferior outcomes after
      hepatectomy for metachronous CLM.

PMID- 22968065
TI  - Surgeon knowledge contributes to the relationship between surgeon volume and
      patient outcomes in rectal cancer.
AB  - OBJECTIVE: To determine whether surgeon knowledge contributes to the relationship
      between surgeon procedure volume and patient outcomes in rectal cancer.
      BACKGROUND: Although previous research has shown that treatment by high-volume
      surgeons is associated with improved outcomes among patients with rectal cancer,
      the mechanisms for such an association are not well understood. METHODS: In 2009,
      a mail survey with 8 questions pertaining to rectal cancer care was created,
      modified for content validity, and sent to all general surgeons in Nova Scotia,
      Canada. Patients with rectal cancer, who were treated by the survey respondents
      between July 1, 2002, and June 30, 2006, were identified retrospectively, and a
      comprehensive standardized review of medical records was used to collect outcome
      data for this population-based cohort. The association between surgeon survey
      score (dichotomized into high- and low-score groups on the basis of the median
      score), surgeon procedure volume, and patient outcomes was examined. RESULTS: Of
      521 patients who underwent treatment with curative intent from July 1, 2002, to
      June 30, 2006, 377 patients (72%) were treated by 25 surgeons who responded to
      the survey. After controlling for patient and tumor factors, patients treated by
      high-volume surgeons were more likely to receive a total mesorectal excision
      (TME) [odds ratio (OR) = 3.89; 95% confidence interval (CI), 2.20-5.83], more
      likely to undergo an adequate lymph node harvest (OR = 3.67; 95%CI, 2.36-5.70),
      less likely to have a permanent colostomy (OR = 0.53; 95%CI, 0.30-0.93), and less
      likely to develop local recurrence (HR = 0.54; 95%CI, 0.29-0.99). When surgeon
      survey score was included in the multivariate regression models, the relationship
      between surgeon procedure volume and permanent colostomy was diminished. There
      was a significant interaction between surgeon survey score and surgeon volume for
      the outcomes of use of TME (P < 0.01) and local recurrence (P = 0.01).
      CONCLUSIONS: These data suggest that surgeon knowledge may, at least in part,
      explain surgeon volume-associated differences in rectal cancer outcomes.

PMID- 22968066
TI  - Laparoscopic segmentectomy of the liver: from segment I to VIII.
AB  - OBJECTIVE: To evaluate the surgical techniques necessary to complete total
      laparoscopic segmentectomy (LS) of all liver segments (I-VIII). BACKGROUND: When
      compared to open surgery, preservation of functional hepatic volume may be more
      difficult during laparoscopic hepatectomy. LS is a possible alternative to
      hemihepatectomy, but laparoscopic surgical techniques to complete anatomically
      accurate segmentectomy have not yet been well established. METHODS: Data of a
      total of 342 consecutive patients who underwent laparoscopic hepatectomy were
      reviewed. LS was defined as complete removal of the Couinaud's segment, in which
      the corresponding hepatic veins are exposed on the raw surface. The laparoscopic
      approach was facilitated by using intraoperative ultrasonography for each segment
      and by placing intercostal trocars to expose the root of the right hepatic vein
      for segmentectomy VII and VIII. RESULTS: LS was completed in 62 patients: 36
      segmentectomies (from I-VIII), 16 bisegmentectomies of the right lobe, and 10
      subsegmentectomies were performed. Conversion to open surgery was required in 3
      patients (IVa, VI, and VII). When 26 LS of the superior/posterior hepatic
      (sub)segments (I, IVa, VII, and VIII) were compared with the remaining 36 LS, the
      former group required a longer operation time (240 [132-390] minutes vs 155 [90
      360]) minutes, P < 0.01) and showed an increased amount of blood loss (350 [20
      1500] mL vs 100 [10-1100] mL, P = 0.02). CONCLUSIONS: LS is feasible and has
      become an essential surgical technique that can minimize the loss of functional
      liver volume without reducing curability, although further technical advancements
      are needed to enhance the accuracy of the resection, especially for the
      superior/posterior segments.

PMID- 22968067
TI  - Proposal for a multifactorial prognostic score that accurately classifies 3
      groups of gastric carcinoma patients with different outcomes after neoadjuvant
      chemotherapy and surgery.
AB  - OBJECTIVE: We have developed a multifactorial histopathological prognostic score
      (PRSC) for patients with gastric cancer treated with neoadjuvant chemotherapy
      before surgery for the accurate discrimination of patient subgroups with
      differing outcomes. BACKGROUND: For patients with gastric cancer who undergo
      multimodal treatment, the postoperative staging classifications used for
      nontreated tumors may not accurately predict patient prognosis. METHODS: We
      evaluated 428 gastric carcinoma specimens after a cisplatin-based chemotherapy.
      The factors for the Union for International Cancer Control/American Joint
      Committee on Cancer (UICC/AJCC) ypT-category, ypN-category, and histopathological
      tumor regression were assigned a value from 1 to 3 as follows: ypT0 to 2 = 1
      point; ypT3 = 2 points; ypT4 = 3 points; ypN0 = 1 point; ypN1 to 2 = 2 points;
      ypN3a to 3b = 3 points; less than 10% residual tumor per tumor bed = 1 point; 10%
      to 50% residual tumor per tumor bed = 2 points; and greater than 50% residual
      tumor per tumor bed = 3 points. A 3-tiered PRSC based on the sum value was
      established (group A: 3-4 points; group B: 5-7 points; group C: 8-9 points) and
      was found to correlate with patient prognosis. RESULTS: The PRSC showed a clear
      discrimination of 3 significantly different prognostic groups (group A: 76
      patients; group B: 210 patients; group C: 142 patients; P < 0.001). In
      multivariate analyses, including the completeness of resection, tumor diameter,
      lymphatic vessel invasion, tumor grading, and Lauren classification, the PRSC was
      the only independent prognostic factor for overall survival (hazard ratio [HR] =
      2.03; 95% confidence intervals [CI], 1.49-2.78; P < 0.001). It was slightly
      superior to the UICC/AJCC staging system (HR = 1.66; 95% CI, 1.20-2.27; P =
      0.002) when analyzed with tumor regression as an additional independent factor
      (HR = 1.27; 95% CI, 1.01-1.62; P = 0.044) included in the analysis. CONCLUSIONS:
      The proposed PRSC reveals the most accurate prediction of survival for patients
      with gastric carcinoma after neoadjuvant chemotherapy followed by surgery. The
      PRSC clearly identifies 3 subgroups with different prognoses and may be helpful
      for therapeutic decisions.

PMID- 22968068
TI  - Identifying important predictors for anastomotic leak after colon and rectal
      resection: prospective study on 616 patients.
AB  - OBJECTIVE: The purpose of this study was to identify patient, clinical, and
      surgical factors that may predispose patients to anastomotic leak (AL) after
      large bowel surgery. BACKGROUND: Anastomotic leak is still one of the most
      devastating complications following colorectal surgery. Knowledge about factors
      predisposing patients to AL is vital to its early detection, decision making for
      surgical time, managing preoperative risk factors, and postoperative
      complications. METHODS: This was a prospective observational, quality improvement
      study in a cohort of 616 patients undergoing colorectal resection in a single
      institution with the main outcome being AL within 30 days postoperatively. Some
      of the predictor variables were age, sex, Charlson Comorbidity Index (CCI),
      radiation and chemotherapy, immunomodulator medications, albumin, preoperative
      diagnoses, surgical procedure(s), surgical technique (laparoscopic vs open),
      anastomotic technique (staple vs handsewn), number of major arteries ligated at
      surgery, surgeon's experience, presence of infectious condition at surgery,
      intraoperative adverse events, and functional status using 36-Item Short Form
      General Health Survey. RESULTS: Of the 616 patients, 53.4% were female. The
      median age of the patients was 63 years and the mean body mass index was 25.9
      kg/m. Of them, 80.3% patients had laparoscopic surgery and 19.5% had open
      surgery. AL occurred in 5.7% (35) patients. In multivariate analysis, significant
      independent predictors for leak were anastomoses less than 10 cm from the anal
      verge, CCI of 3 or more, high inferior mesenteric artery ligation (above left
      colic artery), intraoperative complications, and being of the male sex.
      CONCLUSIONS: Multiple risk factors exist that predispose patients to ALs. These
      risk factors should be considered before and during the surgical care of
      colorectal patients.

PMID- 22968069
TI  - Volume-based parameters of (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography improve outcome prediction in early-stage non
      small cell lung cancer after surgical resection.
AB  - OBJECTIVE: To evaluate the prognostic significance and predictive performance of
      volume-based parameters of F-fluorodeoxyglucose positron emission
      tomography/computed tomography (F-FDG PET/CT) in early-stage non-small cell lung
      cancer (NSCLC). BACKGROUND: Although surgical resection remains the optimal
      treatment for early-stage NSCLC, approximately 40% of patients with stage I and
      60% of patients with stage II NSCLC relapse and die within 5 years after curative
      resection. Therefore, identification of additional prognostic biomarkers is
      needed to develop risk-adapted treatment strategies. METHODS: We retrospectively
      reviewed 529 consecutive patients with pathologically proven early-stage NSCLC
      who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value
      (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the
      primary tumors were measured. Overall survival (OS) and disease-free survival
      (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of
      PET parameters and other clinicopathological variables was assessed by Cox
      proportional hazards regression analysis. To evaluate and compare the predictive
      performance of PET parameters, time-dependent receiver operating characteristic
      (ROC) curve analysis was used. RESULTS: In the multivariate analyses, volume
      based parameters of PET (MTV and TLG) that were analyzed as continuous variables
      were significantly associated with an increased risk of recurrence (P = 0.001 for
      MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after
      adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax
      analyzed as a continuous variable was not a significant prognostic factor for
      both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve
      analysis, the volume-based parameter of PET showed better predictive performance
      than SUVmax (P < 0.001). CONCLUSIONS: The volume-based parameter of PET is an
      independent prognostic factor for survival in addition to pathological tumor-node
      metastasis stage and a promising tool for better prediction of outcome in
      patients with early-stage NSCLC.

PMID- 22968070
TI  - Single-port donor nephrectomy provides improved patient satisfaction and
      equivalent outcomes.
AB  - OBJECTIVE: Minimally invasive techniques have expanded the donor pool for living
      kidney donation. We changed our approach to single-port donor nephrectomy in 2009
      and have compared outcomes with traditional multiple-port laparoscopic donor
      nephrectomy. BACKGROUND: The development of minimally invasive surgical
      techniques to procure kidneys from living donors has allowed expansion of living
      donor renal transplantation to account for one third of all renal transplants.
      Recent technical advancement allows for the entire surgical procedure to be done
      through a single incision contained within the umbilicus. METHODS: We compared
      outcomes from 135 single-port donor nephrectomies with an immediately preceding
      cohort of 100 multiple-port laparoscopic donor nephrectomies. Survey data were
      collected from both groups to compare outcomes. Additional comparisons were made
      to total center experience with 1300 laparoscopic donor nephrectomies. RESULTS: A
      total of 135 patients completed successful single-port donor nephrectomy without
      major complication or open conversion. Another 16 patients required additional
      port placement because of excessive intra-abdominal fat or limited abdominal
      domain. Compared with multiple-port donor nephrectomy, single-port patients had
      similar operative times to cross clamp (2.8 vs 2.6 hours; P = 0.11) that
      normalized after a learning curve of approximately 50 cases. Recipient creatinine
      levels were similar at 1 week and 1 month posttransplant. Although 36-Item Short
      Form Health Surveys demonstrated no significant differences, additional survey
      data revealed that single-port patients were more satisfied with cosmetic
      outcomes (P < 0.01) and the overall donation process (P = 0.01). Single-port
      approach had similar outcomes compared with all previous laparoscopic donor
      nephrectomies. CONCLUSIONS: Single-port donor nephrectomy can be integrated as a
      standardized approach for renal donation without additional donor risk, and with
      benefits of improved patient satisfaction with cosmetic and overall outcomes.
      Although the primary benefit is cosmetic, (a single incision predominantly
      contained within the umbilicus) outcomes justify application for kidney donors in
      experienced centers and may motivate additional living kidney donation.

PMID- 22968071
TI  - Symbiotic or parasitic? A review of the literature on the impact of fellowships
      on surgical residents.
AB  - OBJECTIVE: We conducted a systematic review of published literature to gain a
      better understanding of the impact of advanced fellowships on surgical resident
      training and education. BACKGROUND: As fellowship opportunities rise, resident
      training may be adversely impacted. METHODS: PubMed, MEDLINE, Scopus, BIOSIS, Web
      of Science, and a manual search of article bibliographies. Of the 139 citations
      identified through the initial electronic search and screened for possible
      inclusion, 23 articles were retained and accepted for this review. Data were
      extracted regarding surgical specialty, methodology, sample population, outcomes
      measured, and results. RESULTS: Eight studies retrospectively compared the eras
      before and after the introduction of a fellowship or trended data over time.
      Approximately half used data from a single institution, whereas the other half
      used some form of national data or survey. Only 3 studies used national case
      data. Fourteen studies looked at general surgery, 6 at obstetrics-gynecology, 2
      at urology, and 1 at otolaryngology. Only one study concluded that fellowships
      have a generally positive impact on resident education, whereas 9 others found a
      negative impact. The remaining 13 studies found mixed results (n = 6) or minimal
      to no impact (n = 7). CONCLUSIONS: The overall impact of advanced surgical
      fellowships on surgical resident education and training remains unclear, as most
      studies rely on limited data of questionable generalizability. A careful study of
      the national database of surgery resident case logs is essential to better
      understand how early surgical specialization and fellowships will impact the
      future of general surgery education.

PMID- 22968072
TI  - Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on
      type 2 diabetes mellitus in morbidly obese subjects.
AB  - OBJECTIVE: To identify the rates and the predictors of long-term remission and
      the recurrence of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass
      (RYGBP) or sleeve gastrectomy (SG). BACKGROUND: The durability of the improvement
      of T2DM after bariatric surgery is not well characterized. METHODS: One hundred
      fifty-three subjects with T2DM (RYGBP: n = 98; SG: n = 55) were evaluated for
      remission and recurrence of the disease throughout 35.4 +/- 13.5 months' follow
      up. The type of surgery, demographic, anthropometric, and biochemical parameters
      were ascertained as predictors of T2DM outcomes. Glucagon-like peptide 1 (GLP-1)
      responses after a standard mixed liquid meal were compared between patients
      presenting with T2DM remission after RYGBP or SG. RESULTS: 75.2% of subjects
      presented with remission of T2DM lasting at least 12 months. However, in 12.1% of
      subjects, T2DM recurred. Regression analysis showed a longer duration of T2DM (P
      = 0.006), a higher presurgical glycated hemoglobin level (P = 0.019), insulin
      treatment at baseline (P = 0.001), and a lower excess weight loss at last follow
      up visit (P < 0.001) as independent predictors for the lack of T2DM remission.
      Insulin use before surgery (P = 0.005), an older age (P = 0.05), and weight
      regain after remission (P = 0.021) predicted recurrence of the disease. Long-term
      remission of T2DM after SG or RYGBP was associated with a comparably enlarged GLP
      1 response to a standard mixed liquid meal challenge. CONCLUSIONS: Roux-en-Y
      gastric bypass and SG are associated with comparable remission rates of T2DM.
      However, insufficient weight loss or weight regain in those with a more advanced
      disease may hamper the benefits of these surgical techniques on T2DM.

PMID- 22968073
TI  - Pancreatic ductal adenocarcinoma: is there a survival difference for R1
      resections versus locally advanced unresectable tumors? What is a "true" R0
      resection?
AB  - OBJECTIVE: Patients who undergo an R0 resection of their pancreatic ductal
      adenocarcinoma (PDAC) have an improved survival compared with patients who
      undergo an R1 resection. It is unclear whether an R1 resection confers a survival
      benefit over locally advanced (LA) unresectable tumors. Our aim was to compare
      the survival of patients undergoing an R1 resection with those having LA tumors
      and to explore the prognostic significance of a 1-mm surgical margin. METHODS:
      Clinicopathologic data from a pancreatic cancer database between January 1993 and
      July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic
      disease at exploration. RESULTS: A total of 1705 patients were evaluated for PDAC
      in the Department of Surgery. Of the 1084 (64%) patients who were surgically
      explored, 530 (49%) were considered unresectable (286 locally unresectable, 244
      with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had
      an R1 resection. Patients undergoing an R1 resection had a slightly longer
      survival compared with those who had locally advanced unresectable cancers (14 vs
      11 months; P < 0.001). Patients with R0 resections had a favorable survival
      compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival
      after resections with 1-mm margin or less (R0-close) were similar to R1
      resections: both groups had a significantly shorter median survival than patients
      with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months,
      respectively; P < 0.001). CONCLUSIONS: Patients undergoing an R1 resection still
      have an improved survival compared with patients with locally advanced
      unresectable pancreatic adenocarcinoma. R0 resections have an improved survival
      compared with R1 resections, but this survival benefit is lost when the tumor is
      within 1 mm of the resection margin.

PMID- 22968074
TI  - A systematic review of the effectiveness, compliance, and critical factors for
      implementation of safety checklists in surgery.
AB  - OBJECTIVE: A systematic literature review was conducted to assess the
      effectiveness of, compliance with, and critical factors for the implementation of
      safety checklists in surgery. BACKGROUND: With the aim of increasing patient
      safety, checklists have gained growing attention. Information about
      effectiveness, compliance, and critical factors for implementation is crucial for
      whether and which of the available instruments to use. DATA SOURCES: Medline
      including Premedline (OvidSP), Embase, and Cochrane Collaboration Library, hand
      search, a search of reference lists of key articles, and tables of content. STUDY
      SELECTION: Electronic databases returned 4997 citations, of which 84 articles
      were chosen for full-text review. Finally, 22 articles were included in this
      review. DATA EXTRACTION: Data relating to care setting, study methods and design,
      sample population, survey response rate, type of checklist, aim, effectiveness,
      compliance, attitudes, and critical factors were extracted from the studies. A
      random effects meta-analysis of effectiveness data was conducted if 2 or more
      studies reported a specified outcome. RESULTS: With the use of checklists, the
      relative risk for mortality is 0.57 [95% confidence interval (CI): 0.42-0.76] and
      for any complications 0.63 (95% CI: 0.58-0.67). The overall compliance rate
      ranged from 12% to 100% (mean: 75%) and for the Time Out from 70% to 100% (mean:
      91%). CONCLUSIONS: Checklists are effective and economic tools that decrease
      mortality and morbidity. Compliance of surgical staff with checklists was good
      overall. Further research in particular relating to implementation is needed.

PMID- 22968075
TI  - Prognostic impact of N staging in 715 medullary thyroid cancer patients: proposal
      for a revised staging system.
AB  - OBJECTIVE: This institutional study aimed at quantifying a medullary thyroid
      cancer (MTC) patient's risk of lung, liver, or bone metastasis. BACKGROUND:
      Without quantitative information regarding risk factors for lung, liver, and bone
      metastasis, risk stratification is liable to be haphazard, resulting in poor cost
      effectiveness of screening programs. METHODS: Included in this study were 715
      patients with MTC for whom histopathologic information was available for each
      lymph node removed. RESULTS: Seventy-two patients (10.1%) were diagnosed with
      lung metastasis, 58 patients (8.1%) with liver metastasis, and 34 patients (4.8%)
      with bone metastasis. Multivariate analyses were limited to patients revealing no
      more than 1 type of distant metastasis to avoid confounding by other distant
      metastasis. Extrathyroidal extension and 1 to 10 involved nodes indicated a small
      risk of lung metastasis [3%-4%; odds ratio (OR) 3-4], tumors greater than 40 mm
      and 11 to 20 involved nodes implied an intermediate risk (13%; OR 6), and more
      than 20 involved nodes entailed a high risk (26%-30%; OR 14-16). In the
      multivariate logistic regressions on liver and bone metastasis, in which the
      number of involved nodes was omitted on statistic grounds, extrathyroidal
      extension signified a strong risk of liver metastasis (19%, OR 23), whereas no
      clinical-pathologic variables were significantly associated with bone metastasis.
      Cumulative rates of lung, liver, and bone metastasis, plotted against the number
      of lymph node metastases, were similar. DISCUSSION: N categories encompassing 1
      to 10 (N1), 11 to 20 (N2), and more than 20 (N3) lymph node metastases are
      important prognostic classifiers that should be incorporated into MTC staging
      systems for better risk stratification.

PMID- 22968076
TI  - Scheduled surgery admissions and occupancy at a children's hospital: variation we
      can control to improve efficiency and value in health care delivery.
AB  - OBJECTIVE: Describe variability in admission, discharge, and occupancy patterns
      for surgical patients at a large children's hospital and assess the relationship
      between scheduled admissions and occupancy. BACKGROUND: High hospital occupancy
      degrades quality of care and access, whereas low levels of occupancy use hospital
      resources inefficiently. Variability in scheduling patients for surgical
      procedures may affect occupancy and be amenable to alteration. METHODS: This is a
      retrospective administrative data analysis that took place at 1 urban, tertiary
      care children's hospital. A total of 8552 surgical patients hospitalized from
      July 1, 2009, to June 30, 2010, were included in the analysis, and admission
      discharge-transfer data for 1 fiscal year were abstracted for analysis of
      admission and occupancy patterns. RESULTS: Among 6257 surgical admissions for non
      intensive care unit (ICU) patients, 49% were emergent and 51% were scheduled.
      Variation in admission volume by day of week was more than 3 times higher for
      scheduled admissions than for emergent admissions. For non-ICU surgical patients
      with length of stay 7 days or less (97%), Mondays and Tuesdays generated 42% of
      scheduled patient occupancy time. Thursdays and Fridays often had high occupancy
      of surgical patients (>90% of designated beds filled), whereas Saturdays,
      Sundays, and Mondays were often at low occupancy for those beds (<80% filled).
      Only 20% of all days in the year had designated non-ICU surgery beds with
      occupancy between 80% and 95%. CONCLUSIONS: Scheduled admissions contribute
      significantly to variability in occupancy. Predictable patterns of admissions
      lead to high occupancy on some days and unused capacity on others, with few days
      being at an optimal level of occupancy. These predictable patterns suggest
      opportunities to improve hospital operations with changes in scheduled admission
      patterns, which present a different problem than random demand.

PMID- 22968077
TI  - Lc3 over-expression improves survival and attenuates lung injury through
      increasing autophagosomal clearance in septic mice.
AB  - OBJECTIVE: To clarify the role of autophagy in sepsis-induced lung injury.
      BACKGROUND: The role of autophagy as a protective or maladaptive response in lung
      cells during sepsis has not yet been determined. The lack of specificity of the
      autophagic process has driven the development of new approaches that assess
      autophagosomes from formation to fusion with lysosomes. METHODS: Sepsis was
      induced by cecal ligation and puncture (CLP). The autophagic process was
      manipulated using the pharmacological inhibitors of the autophagy pathway. Green
      fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3)
      transgenic mice were further used to determine the role of autophagy. RESULTS:
      The formation of autophagosomal protein LC3-II progressively accumulated in the
      lungs over 24 hours after CLP, with the Lc3 gene expression returning to baseline
      levels at 24 hours. Autophagosome-lysosome fusion, however, gradually decreased
      from 8 to 24 hours after CLP, suggesting impaired clearance of autophagosomes
      rather than upregulation of autophagy in the septic lung. In contrast, transgenic
      mice overexpressing the Lc3 gene exhibited increased clearance of autophagosomes
      and improved survival after CLP. This protective effect was also seen in
      decreased cell death, inflammatory responses, neutrophil accumulation, albumin
      leakage, and edema formation. However, blockade of autophagosome-lysosome fusion
      with bafilomycin A1 abolished the protective effects in transgenic mice. This
      indicates that Lc3 transgene attenuates lung injury/inflammation in sepsis,
      possibly through increasing the clearance of autophagosomes. CONCLUSIONS:
      Autophagy in the septic lung represents a protective response. However,
      autophagy, by virtue of excessive autophagosome accumulation, may play a
      maladaptive role in the late stage of sepsis, leading to acute lung injury.

PMID- 22968078
TI  - Should the portal vein be routinely resected during pancreaticoduodenectomy for
      adenocarcinoma?
AB  - INTRODUCTION: In pancreatic adenocarcinoma (PA), a margin negative resection (R0)
      is critical for long-term survival. BACKGROUND: Although pancreaticoduodenectomy
      (PD) with en-bloc portal vein/superior mesenteric vein (PV/SMV) resection is used
      in patients with venous involvement by tumor, its utility in patients with no
      venous involvement is unknown. This study examines survival in patients with no
      venous involvement who had PD with PV/SMV resection. METHODS: From 2000 to 2010,
      34 patients had PD with PV/SMV resection for resectable PA on preoperative
      staging. Fifteen patients (44%) had histological venous involvement and 19 (56%)
      had no histological involvement (-PV/SMV group). We matched 1:1 the -PV/SMV group
      (n = 19) with 19 contemporaneous PA patients who had a standard PD (control
      group) for age, tumor stage, tumor size, lymph node invasion, lymph node ratio,
      perineural invasion, margins status, and carbohydrate antigen 19-9 (CA 19-9)
      levels. RESULTS: No differences were noted between the -PV/SMV group (n = 19) and
      the matched control group (n = 19) in morbidity, mortality, reoperation rate, or
      length of hospital stay. Median survival (42 months vs. 22 months, P = 0.02) and
      overall 3-year survival (60% vs. 31%, P = 0.03) were significantly longer in the 
      PV/SMV group compared with the control group. CONCLUSIONS: Patients with PA and
      no venous involvement who had PD with PV/SMV resection had a significantly longer
      overall survival than patients in a matched control group who had PD without
      venous resection.

PMID- 22968079
TI  - Predictors of surgery in patients with severe acute pancreatitis managed by the
      step-up approach.
AB  - BACKGROUND: Initial management of severe acute pancreatitis (SAP) is
      conservative. As a step-up approach, percutaneous catheter drainage (PCD) with
      saline irrigation is reported to be effective. Factors leading to surgery are
      unclear. METHODS: In this ongoing prospective study, 70 consecutive patients with
      SAP were recruited. As a step-up approach, all patients initially received
      medical management and later underwent PCD and surgery as per the indication.
      RESULTS: Of the 70 consecutive patients with SAP, 14 were managed medically, 29
      managed with PCD alone, whereas 27 required surgery after initial PCD. Sepsis
      reversal was achieved with PCD alone in 62.5%. The curative efficacy of PCD alone
      was in 27 patients (48%). Overall mortality in the whole group was 24%. On
      univariate analysis, factors significantly affecting surgical intervention
      included initial acute physiology and chronic health evaluation (APACHE) II
      score, APACHE II score at first intervention, sepsis reversal by PCD within a
      week, number of organs failed, organ failure within a week of the onset of
      disease, number of bacteria isolated per patient, renal failure, respiratory
      failure, Escherichia coli, computerized tomography severity index score at
      admission, parenteral nutrition requirement before or after radiological
      intervention, maximum extent of necrosis of more than 50% of the pancreas, and
      extrapancreatic necrosis. On multivariate analysis, renal failure (P = -0.03),
      APACHE II score at first intervention (P = -0.006), and the number of bacteria
      isolated per patient (P = -0.01) remained independent predictors of surgery. An
      APACHE II score of more than 7.5 at first intervention (PCD) had the ability to
      predict surgery with a sensitivity of 88.9% and a specificity of 69%.
      CONCLUSIONS: PCD reversed sepsis in 62% and avoided surgery in 48% of the
      patients. Reversal of sepsis within a week of PCD, APACHE II score at first
      intervention (PCD), and organ failure within a week of the onset of disease could
      predict the need for surgery in the early course of disease.

PMID- 22968080
TI  - Breast cancer molecular phenotype and the use of HER2-targeted agents influence
      the accuracy of breast MRI after neoadjuvant chemotherapy.
AB  - OBJECTIVE: To investigate whether the accuracy of magnetic resonance imaging
      (MRI) after neoadjuvant systemic therapy (NST) is affected by molecular features
      of primary breast cancer and the use of human epidermal growth factor receptor 2
      (HER2)-targeted agents. BACKGROUND: Improved understanding of factors affecting
      the accuracy of breast MRI after NST can lead to more tailored use of MRI in
      deciding surgical extent after NST. METHODS: We analyzed the imaging and
      clinicopathological data of 463 patients who underwent NST. We aimed to
      investigate whether the molecular subtypes, and the use of targeted therapies,
      were associated with changes in the accuracy of MRI predicting residual tumor
      extent. RESULTS: The accuracy of MRI predicting the residual tumor extent was
      most accurate in triple-negative breast cancer and was least accurate in Luminal
      A subtype (Pearson correlation coefficient of 0.754 and 0.531, respectively).
      Multivariate analysis suggested estrogen receptor (ER) status as an independent
      factor influencing the MRI accuracy. In HER2-amplified tumors, the use of HER2
      targeted agents was associated with a less accurate MRI prediction. CONCLUSIONS:
      The accuracy of MRI in predicting residual tumor extent was lowest in ER-positive
      tumors treated with NST. In HER2-positive tumors, the use of HER2-targeted agents
      resulted in a less accurate MRI after NST. These factors should be considered for
      deciding the extent of breast conservation after neoadjuvant chemotherapy.

PMID- 22968081
TI  - High risk of rectal cancer and of metachronous colorectal cancer in probands of
      families fulfilling the Amsterdam criteria.
AB  - OBJECTIVE: To investigate the risk of metachronous colorectal cancer (CRC), its
      impact on survival, and the risk of rectal cancer in a cohort of probands meeting
      the Amsterdam criteria. BACKGROUND: Several determinants of decision-making for
      the management of CRC in patients with a putative diagnosis of Lynch syndrome are
      scarcely defined, and many of them undergo segmental bowel resection instead of
      the advised total colectomy. METHODS: A retrospective cohort study was conducted
      on 65 probands of the Amsterdam-positive families who had surgery for primary CRC
      and at least 5-year surveillance thereafter. The rates of metachronous CRC and of
      rectal cancer were evaluated, together with their association with preoperatively
      available clinical predictors. Differences in overall survival between patients
      with and without metachronous CRC were evaluated using a time-dependent Cox
      model. RESULTS: Seventeen patients (26.2%) had metachronous CRC. No clinical
      feature was associated with an increased risk of its development. The risk of
      death in patients with metachronous CRC was 6-fold increased. Neither a 2-year
      interval endoscopic surveillance after surgery, nor total colectomy was
      associated with a significant reduction in metachronous CRC. Eighteen patients
      (23.7%) had rectal cancer at first presentation, 5 patients of the remainder
      (10.6%) developed rectal cancer after primary colon resection. Two patients
      undergoing total colectomy developed a metachronous rectal cancer (18.2%). A
      first-degree family history of rectal cancer was associated with an increased
      risk of rectal cancer. CONCLUSIONS: Probands of families fulfilling the Amsterdam
      criteria carry a high risk of rectal cancer and of metachronous CRC. Total
      proctocolectomy, or total colectomy and a 1-year interval of proctoscopic
      surveillance should be advised when a high risk of rectal cancer can be
      predicted.

PMID- 22968083
TI  - Microwave-assisted one-step extraction-derivatization for rapid analysis of fatty
      acids profile in herbal medicine by gas chromatography-mass spectrometry.
AB  - A rapid and practical microwave-assisted one-step extraction-derivatization
      (MAED) method was developed for gas chromatography-mass spectrometry analysis of
      fatty acids profile in herbal medicine. Several critical experimental parameters
      for MAED, including reaction temperature, microwave power and the amount of
      derivatization reagent (methanol), were optimized with response surface
      methodology. The results showed that the chromatographic peak areas of total
      fatty acids and total unsaturated fatty acids content obtained with MAED were
      markedly higher than those obtained by the conventional Soxhlet or microwave
      extraction and then derivatization method. The investigation of kinetics and
      thermodynamics of the derivatization reaction revealed that microwave assistance
      could reduce activation energy and increase the Arrhenius pre-exponential factor.
      The MAED method simplified the sample preparation procedure, shortened the
      reaction time, but improved the extraction and derivatization efficiency of
      lipids and reduced ingredient losses, especially for the oxidization and
      isomerization of unsaturated fatty acids. The simplicity, speed and practicality
      of this method indicates great potential for high throughput analysis of fatty
      acids in natural medicinal samples.

PMID- 22968084
TI  - Development of a novel plasmid as a shuttle vector for heterologous gene
      expression in Mycoplasma yeatsii.
AB  - A circular plasmid, pMyBK1, was detected in Mycoplasma yeatsii strain GIH(T).
      Analysis of the sequence of the 3432-bp replicon identified two predicted open
      reading frames (ORFs), one with sequence similarity to multiple plasmid
      mobilization proteins and one that matches only to hypothetical ORFs encoded by
      integrated chromosomal elements in the sequenced genomes of two Mycoplasma
      species. Shuttle vectors were constructed in Escherichia coli which could be
      introduced into M. yeatsii at high efficiency (10(4)-10(5) per MUg DNA) by
      electroporation. Independent deletion analysis of the two ORFs disclosed that
      whereas mob was dispensable, orf2 was necessary for plasmid replication or
      maintenance. The absence of plasmid-encoded database matches for ORF2 indicates
      that pMyBK1 represents a novel plasmid family. One shuttle vector was used to
      demonstrate heterologous expression of the Mycoplasma fermentans malp gene and
      was stable during multiple passages. The host-plasmid system described has
      potential application for genetic manipulation in a genus for which few
      replicative vectors are available.

PMID- 22968082
TI  - Influence of stimulant-induced hyperactivity on social approach in the BTBR mouse
      model of autism.
AB  - Translational research is needed to discover pharmacological targets and
      treatments for the diagnostic behavioral domains of autism spectrum disorders.
      Animal models with phenotypic relevance to diagnostic criteria offer clear
      experimental strategies to test the efficacy and safety of novel treatments.
      Antagonists of mGluR5 receptors are in clinical trials for Fragile X syndrome and
      under investigation for the treatment of autism spectrum disorders. However, in
      preclinical studies of mGluR5 compounds tested in our laboratory and others,
      increased locomotion following mGluR5 modulation has been observed. Understanding
      the influence of general activity on sociability and repetitive behaviors will
      increase the accuracy of interpretations of positive outcomes measured from
      pharmacological treatment that produces locomotor activating or sedating effects.
      In the present studies, dose-response curves for d-amphetamine (AMPH)-induced
      hyperlocomotion were similar in standard B6 mice and in the BTBR mouse model of
      autism. AMPH produced significant, robust reductions in the high level of
      repetitive self-grooming that characterizes BTBR, and also reduced the low
      baseline grooming in B6, indicating that AMPH-induced hyperlocomotion competes
      with time spent engaged in self-grooming. We then tested AMPH in B6 and BTBR on
      the 3-chambered social approach task. One component of sociability, the time
      spent in the chamber with the novel mouse, in B6 mice was reduced, while the
      sniffing time component of sociability in BTBR mice was enhanced. This finding
      replicated across multiple cohorts treated with AMPH and saline vehicle. In-depth
      analysis revealed that AMPH increased the number and decreased the duration of
      sniffing bouts in BTBR, suggesting BTBR treated with AMPH mostly engaged in brief
      sniffs rather than true social interactions with the novel mouse during the
      social approach task. Our data suggest that compounds with stimulant properties
      may have some direct benefits on reducing repetitive behaviors in autism spectrum
      disorders, particularly in the subset of autistic individuals with hyperactivity.
      This article is part of the Special Issue entitled 'Neurodevelopmental
      Disorders'.

PMID- 22968085
TI  - Estimating glomerular filtration rate (GFR) in diabetes: the performance of MDRD
      and CKD-EPI equations in patients with various degrees of albuminuria.
AB  - OBJECTIVES: The aim of this study was to compare the performance of Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in
      Renal Disease Study (MDRD) equations in estimating GFR in a large cohort of
      diabetic patients with various degrees of albuminuria. DESIGN AND METHODS: In a
      group of 842 diabetic patients GFR was estimated from standardized creatinine,
      with MDRD-Study and CKD-EPI equations, and their performance evaluated regarding
      clinical stages of albuminuria and chronic kidney disease (CKD). RESULTS:
      Patients with normoalbuminuria had higher eGFR when calculated by CKD-EPI, than
      MDRD-Study equation [median (IQR): 103 (91-115) vs 97 (85-113)mL/min/1.73 m(2),
      P=0.006, n=364], which significantly influenced the prevalence of stage 1 CKD
      [eGFR>90 mL/min/1.73 m(2): 76.7% (CKD-EPI) vs. 65.1% (MDRD-Study), P=0.005].
      There were no differences between the eGFR values derived by two equations in
      patients with micro- and macroalbuminuria, and more advanced staging of CKD.
      CONCLUSION: CKD-EPI equation might be a superior surrogate marker of GFR in
      patients with normoalbuminuria and hyperfiltration and could be used as a
      screening tool for early renal impairment in diabetes. It's validity as a marker
      of progression of diabetic nephropathy merits further investigation.

PMID- 22968087
TI  - Polymorphisms of the T-cell immunoglobulin and mucin domain molecule-3 are not
      associated with autoimmune Graves' disease in a Chinese Han Population.
AB  - OBJECTIVES: This study aimed to investigate the association between polymorphisms
      of T-cell immunoglobulin and mucin domain molecule-3 (TIM-3) and Graves' disease
      (GD) in a Chinese population. DESIGN AND METHODS: Genomic DNA was extracted from
      peripheral blood cells of the 182 GD patients and 150 control subjects. The TIM-3
      gene polymorphic sites were genotyped. We also analyzed the relationships between
      the genotypes of each SNP and serum specific clinical variables. To detect
      whether the variants were associated with the TIM-3 expression, we further
      studied 40 patients by using the method of real-time quantitative reverse
      transcription polymerase chain reaction (real-time RT-PCR). RESULTS: The genotype
      and allele frequency of each polymorphic site were not significantly different
      between GD and control individuals. Furthermore, it also showed no relationship
      between the variants and TIM-3 mRNA expression. CONCLUSIONS: Our results
      demonstrated that the polymorphisms of TIM-3 gene may not contribute to GD
      susceptibility in the Chinese Han population.

PMID- 22968086
TI  - Effectiveness of practices to reduce blood sample hemolysis in EDs: a laboratory
      medicine best practices systematic review and meta-analysis.
AB  - OBJECTIVE: To complete a systematic review of emergency department (ED) practices
      for reducing hemolysis in blood samples sent to the clinical laboratory for
      testing. RESULTS: A total of 16 studies met the review inclusion criteria (12
      published and 4 unpublished). All 11 studies comparing new straight needle
      venipuncture with IV starts found a reduction in hemolysis rates, [average risk
      ratio of 0.16 (95% CI=0.11-0.24)]. Four studies on the effect of venipuncture
      location showed reduced hemolysis rates for the antecubital site [average risk
      ratio of 0.45 (95% CI=0.35-0.57]. CONCLUSIONS: Use of new straight needle
      venipuncture instead of IV starts is effective at reducing hemolysis rates in
      EDs, and is recommended as an evidence-based best practice. The overall strength
      of evidence rating is high and the effect size is substantial. Unpublished
      studies made an important contribution to the body of evidence. When IV starts
      must be used, observed rates of hemolysis may be substantially reduced by placing
      the IV at the antecubital site.

PMID- 22968088
TI  - A tet(S/M) hybrid from CTn6000 and CTn916 recombination.

PMID- 22968090
TI  - Use of endovascular therapy for peripheral arterial lesions: an analysis of the
      National Trauma Data Bank from 2007 to 2009.
AB  - BACKGROUND: An endovascular approach is increasingly used for the treatment of
      peripheral arterial trauma (PAT), but evidence supporting this approach is
      lacking. The objective of our study was to assess outcomes for endovascular
      repair (ER) versus operative repair (OR) in PAT. METHODS: We used the National
      Trauma Data Bank from 2007 to 2009 for our analysis, comparing in-hospital
      morbidity and mortality for all adult patients undergoing ER versus OR for PAT of
      the upper and lower extremities. Unadjusted and risk-adjusted generalized linear
      models were performed, with multiple imputation techniques being used to replace
      missing values. RESULTS: Of 8,977 patients, 531 (5.9%) underwent ER. Most
      patients were male (77.1%) and Caucasian (42.6%), with a mean age of 34.7 years
      (standard deviation: 14.8). ER was performed more commonly for lower- (n = 370,
      10.4%) than upper-extremity lesions (n = 161, 3.0%, P < 0.001). Risk-adjusted
      analysis showed that ER patients had significantly greater injury severity scores
      (P < 0.001), were more likely to suffer a blunt (vs. penetrating) mechanism of
      injury (P < 0.001), and were more likely to have multiple comorbid illnesses (P <
      0.001) than OR patients. Overall, risk-adjusted complications were less frequent
      after ER than OR (risk-adjusted OR: 0.79, P = 0.05), whereas in-hospital
      mortality between the two groups did not differ (risk-adjusted OR: 1.10, P =
      0.59). Length of hospital stay was shorter among ER patients (adjusted mean
      difference: 0.78 days, P < 0.001), whereas length of intensive care unit stay did
      not differ between the two groups (P = 0.44). CONCLUSIONS: ER appears to be a
      viable option for patients with PAT. Further research is needed to identify
      potential subgroups of PAT patients in whom ER may be superior to OR.

PMID- 22968092
TI  - Interaction between dorsal and ventral processing streams: where, when and how?
AB  - The execution of complex visual, auditory, and linguistic behaviors requires a
      dynamic interplay between spatial ('where/how') and non-spatial ('what')
      information processed along the dorsal and ventral processing streams. However,
      while it is acknowledged that there must be some degree of interaction between
      the two processing networks, how they interact, both anatomically and
      functionally, is a question which remains little explored. The current review
      examines the anatomical, temporal, and behavioral evidence regarding three
      potential models of dual stream interaction: (1) computations along the two
      pathways proceed independently and in parallel, reintegrating within shared
      target brain regions; (2) processing along the separate pathways is modulated by
      the existence of recurrent feedback loops; and (3) information is transferred
      directly between the two pathways at multiple stages and locations along their
      trajectories. 

PMID- 22968089
TI  - Effects of metabotropic glutamate receptor ligands on male sexual behavior in
      rats.
AB  - Metabotropic glutamate receptors (mGluRs), particularly mGluR2/3, mGluR5 and
      mGluR7, have received much attention in medication development for the treatment
      of drug addiction and other neuropsychiatric diseases. However, little is known
      as to whether mGluR ligands also alter natural sexual behavior, a possible
      unwanted effect when used in humans. In the present study, we used classical
      copulatory behaviors to evaluate the effects of LY379268 (a selective mGluR2/3
      agonist), MPEP (a selective mGluR5 antagonist) and AMN082 (a selective mGluR7
      agonist), on male sexual performance in rats. We found that systemic
      administration of LY379268 (1, 3 mg/kg, i.p.) had no effect, while MPEP (20
      mg/kg, but not 10 mg/kg, i.p.) and AMN082 (10, 20 mg/kg, but not 3 mg/kg)
      produced a significant and dose-dependent reduction in both sex-seeking and sex
      performance behaviors, manifested as an increase in mount or intromission latency
      and time required for ejaculation, and a reduction in mount or intromission
      frequency. This inhibition lasted for about 30-60 min. These findings suggest
      that compounds that target mGluR5 or mGluR7, but not mGluR2/3, may have short
      term inhibitory effects on male sexual performance. This article is part of a
      Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22968093
TI  - Synthesis and characteristics of Ag/Pt bimetallic nanocomposites by arc-discharge
      solution plasma processing.
AB  - Arc discharge in solution, generated by applying a high voltage of unipolar
      pulsed dc to electrodes of Ag and Pt, was used as a method to form Ag/Pt
      bimetallic nanocomposites via electrode erosion by the effects of the electric
      arc at the cathode (Ag rod) and the sputtering at the anode (Pt rod). Ag/Pt
      bimetallic nanocomposites were formed as colloidal particles dispersed in
      solution via the reduction of hydrogen radicals generated during discharge
      without the addition of chemical precursor or reducing agent. At a discharge time
      of 30 s, the fine bimetallic nanoparticles with a mean particle size of
      approximately 5 nm were observed by transmission electron microscopy (TEM). With
      increasing discharge time, the bimetallic nanoparticle size tended to increase by
      forming an agglomeration. The presence of the relatively small amount of Pt
      dispersed in the Ag matrix could be observed by the analytical mapping mode of
      energy-dispersive x-ray spectroscopy and high-resolution TEM. This demonstrated
      that the synthesized particle was in the form of a nanocomposite. No
      contamination of other chemical substances was detected by x-ray photoelectron
      spectroscopy. Hence, solution plasma could be a clean and simple process to
      effectively synthesize Ag/Pt bimetallic nanocomposites and it is expected to be
      widely applicable in the preparation of several types of nanoparticle.

PMID- 22968094
TI  - Poor discriminatory function for endoscopic skills on a computer-based simulator.
AB  - BACKGROUND: Computer-based endoscopy simulators may enable trainees to learn and
      develop technical skills before performing on patients. Simulators require
      validation as adequate models of live endoscopy before being used for training or
      assessment purposes. OBJECTIVE: To evaluate content and criterion validity of the
      CAE EndoscopyVR Simulator colonoscopy and EGD modules as predictors of clinical
      endoscopic skills. DESIGN: Prospective, observational, non-randomized, parallel
      cohort study. SETTING: Single academic center with accredited gastroenterology
      training program. PARTICIPANTS: Five novice first-year gastroenterology fellows
      and 6 expert gastroenterology attending physicians. INTERVENTION: Participants
      performed 18 simulated colonoscopies and 6 simulated EGDs. The simulator recorded
      objective performance parameters. Participants then completed feedback surveys.
      MAIN OUTCOME MEASUREMENTS: The 57 objective performance parameters measured by
      the endoscopy simulator were compared between the two study groups. Novice and
      expert survey responses were analyzed. RESULTS: Significant differences between
      novice and expert performance were detected in only 19 of 57 (33%) performance
      metrics. Eight of these 19 (42%) were time-related metrics, such as total
      procedure time, time to anatomic landmarks, and time spent in contact with GI
      mucosa. Of 49 non-time related measures, the few additional statistically
      significant differences between novices and experts involved air insufflation,
      sedation management, endoscope force, and patient comfort. These findings are of
      uncertain clinical significance. Survey data found multiple aspects of the
      simulation to be unrealistic compared with human endoscopy. LIMITATIONS: Small
      sample size. CONCLUSION: The CAE EndoscopyVR Simulator displays poor content and
      criterion validity and is thereby incapable of predicting skill during in vivo
      endoscopy.

PMID- 22968095
TI  - Use of an endobronchial US endoscope in a nearly obstructing esophageal tumor.

PMID- 22968096
TI  - Ectopic spleen presenting as a gastric submucosal tumor.

PMID- 22968098
TI  - Cytoskeleton: actin regulator substitution.

PMID- 22968100
TI  - Effects of two different types of fast food on postprandial metabolism in normal
      and overweight subjects.
AB  - BACKGROUND/OBJECTIVES: The aim was to investigate the effects of a conventional
      and an unconventional fast-food meal on postprandial metabolism in normal and in
      overweight subjects. SUBJECTS/METHODS: Twenty-five healthy normal (n = 12) and
      overweight (n = 13) volunteers (21-39 years) participated in this randomized,
      dietary cross-over study and received two test meals (matched in energy and
      energy giving nutrients) after an overnight fast with 1 week between test days.
      The conventional fast-food meal was a hamburger meal (hamburger, bacon, cola
      drink, calculated glycemic load = 48.7), the unconventional fast food was a
      salmonburger meal (fiber-rich sourdough rye bread, salad with vinegar, orange
      juice, glycemic load = 46.0). Blood samples were taken before and after the meal
      and analyzed for glucose (before 20, 40, 60 and 80 min) and insulin (before 1, 2
      and 3 h). RESULTS: Postprandial increases in glucose and insulin were 44% lower
      after the unconventional meal (P<0.001 and P = 0.003, respectively). The
      difference between meals in insulin response (that is, conventional meal higher
      than unconventional) correlated with body mass index (BMI) (r = 0.538, P =
      0.006). CONCLUSIONS: Unconventional fast food can have less effect on blood
      insulin and glucose postprandially compared with conventional fast food matched
      in energy and energy giving nutrients. The difference between meals in insulin
      response is associated with higher BMI. Thus, improvement in food quality might
      help to control postprandial increases in blood glucose and blood insulin.

PMID- 22968099
TI  - INSIG2 variants, dietary patterns and metabolic risk in Samoa.
AB  - BACKGROUND/OBJECTIVES: Association of insulin-induced gene 2 (INSIG2) variants
      with obesity has been confirmed in several but not all follow-up studies.
      Differences in environmental factors across populations may mask some genetic
      associations and therefore gene-environment interactions should be explored. We
      hypothesized that the association between dietary patterns and components of the
      metabolic syndrome could be modified by INSIG2 variants. SUBJECTS/METHODS: We
      conducted a longitudinal study of adiposity and cardiovascular disease risk among
      427 and 290 adults from Samoa and American Samoa (1990-1995). Principal component
      analysis on food items from a validated food frequency questionnaire was used to
      identify neotraditional and modern dietary patterns. We explored gene-dietary
      pattern interactions with the INSIG2 variants rs9308762 and rs7566605. RESULTS:
      Results for American Samoans were mostly nonsignificant. In Samoa, the
      neotraditional dietary pattern was associated with lower triglycerides, body mass
      index (BMI), waist circumference, systolic and diastolic blood pressure and
      fasting glucose (all P-for-trend<0.05). The modern pattern was significantly
      associated with higher triglycerides, BMI, waist circumference and lower high
      density lipoprotein-cholesterol (all P-for-trend<0.05). A significant interaction
      for triglycerides was found between the modern pattern and the rs9308762
      polymorphism (P=0.04). Those from Samoa consuming the modern pattern have higher
      triglycerides if they are homozygous for the rs9308762 C allele. CONCLUSIONS: The
      common INSIG2 variant rs9308762 was associated with poorer metabolic control and
      a greater sensitivity of trigylcerides to a modern dietary pattern. Environmental
      factors need to be taken into account when assessing genetic associations across
      and within populations.

PMID- 22968101
TI  - Is the food frequency consumption essential as covariate to estimate usual intake
      of episodically consumed foods?
AB  - BACKGROUNDS/OBJECTIVES: The aim of this paper is to verify the performance of the
      frequency of consumption as variable for prediction of the usual intakes of
      foods. SUBJECTS/METHODS: In total, 725 individuals who answered two
      nonconsecutive 24-h recall and one food frequency questionnaire (FFQ) in the
      'Healthy Survey-Sao Paulo-Brazil'. An additional indicator variable indicating if
      one is usual consumer was created before analyzing. The Multiple Source Method
      and National Cancer Institute method were used to estimate usual intake of
      selected food considering different models of prediction: with no covariates;
      with FFQ; with FFQ plus indicator variable; and with only indicator variable.
      RESULTS: For foods that are consumed every day or almost every day, the inclusion
      of the FFQ and/or the indicator variable as covariates resulted in similar
      percentiles of consumption when compared with the model with no covariates. For
      episodically consumed foods, the models with FFQ plus indicator variable and with
      only indicator variable estimated similar percentiles of intake. CONCLUSIONS: The
      use of the indicator variable instead the FFQ appears as a good alternative to
      estimate usual intake of episodically consumed foods.

PMID- 22968102
TI  - Anti-TNF treatment blocks the induction of T cell-dependent humoral responses.
AB  - OBJECTIVE: Experimental and human data suggest that tumour necrosis factor (TNF)
      blockade may affect B cell responses, in particular the induction of T cell
      dependent (TD) humoral immunity. This study aimed to assess this hypothesis
      directly in patients with arthritis by analysing longitudinally the effect of TNF
      blockade on B cell activation and the maturation of humoral responses against TD
      and T cell-independent vaccines. MATERIALS AND METHODS: Peripheral blood samples
      were obtained from 56 spondyloarthritis patients before and after treatment with
      either non-steroidal anti-inflammatory drug (NSAID) alone or TNF blockers and
      analysed for B cell activation, plasma cell differentiation, germinal centre
      versus extra-follicular B cell maturation, and somatic hypermutation. Vaccine
      responses to hepatitis B and Streptococcus pneumoniae were measured by ELISA.
      RESULTS: TNF blockade augmented B cell activation as reflected by the expression
      of early activation markers, CD40, and costimulatory molecules, without affecting
      differentiation towards plasmablasts. This was associated with a specific
      increase of the unswitched fraction of circulating memory B cells and a decreased
      level of somatic hypermutation in anti-TNF treated patients, indicating an
      impairment of the germinal centre-dependent B cell maturation. In agreement with
      these findings, TNF blockade profoundly suppressed the response to the TD
      vaccination against hepatitis B, whereas the T cell-independent response against
      pneumococcal polysaccharides was only modestly affected. CONCLUSIONS: These data
      indicate that TNF blockade severely impedes the induction of primary TD humoral
      responses, probably by interfering with the germinal centre reaction.

PMID- 22968103
TI  - Effect of cimetidine on pentamidine induced hyperglycemia in rats.
AB  - The antiprotozoal agent pentamidine, used for the treatment of Pneumocystis
      jirovecii pneumonia (PCP), is known to cause abnormalities in blood glucose
      homeostasis, such as hypoglycemia and hyperglycemia. Pentamidine has been
      reported to be a substrate of organic cation transporter 1 (OCT1). We
      investigated the combination effects of cimetidine, an OCT1 inhibitor, on the
      pharmacokinetics of pentamidine and on pentamidine-induced hyperglycemia.
      Pentamidine was infused intravenously to rats for 20 min at a dose of 7.5 or 15
      mg/kg and serum samples were obtained periodically. The serum concentration of
      glucose did not change significantly after pentamidine infusion at 7.5mg/kg,
      while it increased with pentamidine at 15 mg/kg, and the maximal concentration of
      glucose was 167 +/- 36 mg/dl, 30 min after the start of pentamidine infusion.
      Cimetidine (50mg/kg) enhanced the pentamidine-induced elevation of glucose
      concentration and the maximal concentration of glucose was 208 +/- 33 mg/dl in
      the pentamidine 15 mg/kg treated group. Cimetidine combination significantly
      reduced total body clearance of pentamidine and increased pentamidine
      concentrations in the liver, kidneys, and lungs. A significant correlation was
      found between changes in serum glucose concentrations and serum concentrations of
      pentamidine 30 min after the start of pentamidine infusion. These results suggest
      that the hyperglycemic effect of pentamidine is dependent on the concentration of
      pentamidine and can be enhanced by cimetidine combination.

PMID- 22968104
TI  - Characterizing antibody cross-reactivity for immunoaffinity purification of
      analytes prior to multiplexed liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Immunoassays for 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)(2)D]
      lack analytical specificity. We characterized the cross-reactivity of an anti
      1alpha,25(OH)(2)D antibody with purified vitamin D metabolites and used these
      data to map the chemical features of 1alpha,25(OH)(2)D that are important for
      antibody binding. Additionally, we hypothesized that when combined with isotope
      dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS), antibody
      cross-reactivity could be used to semiselectively enrich for structurally similar
      metabolites of vitamin D in a multiplexed assay. METHODS: Sample preparation
      consisted of immunoaffinity enrichment with a solid-phase anti-1alpha,25(OH)(2)D
      antibody and derivatization. Analytes were quantified with LC-MS/MS.
      Supplementation and recovery studies were performed for 11 vitamin D metabolites.
      We developed a method for simultaneously quantifying 25(OH)D(2), 25(OH)D(3),
      24,25(OH)(2)D(3), 1alpha,25(OH)(2)D(2), and 1alpha,25(OH)(2)D(3) that included
      deuterated internal standards for each analyte. RESULTS: The important chemical
      features of vitamin D metabolites for binding to the antibody were (a) native
      orientation of the hydroxyl group on carbon C3 in the A ring, (b) the lack of
      substitution at carbon C4 in the A ring, and (c) the overall polarity of the
      vitamin D metabolite. The multiplexed method had lower limits of quantification
      (20% CV) of 0.2 ng/mL, 1.0 ng/mL, 0.06 ng/mL, 3.4 pg/mL, and 2.8 pg/mL for
      25(OH)D(2), 25(OH)D(3), 24,25(OH)(2)D(3), 1alpha,25(OH)(2)D(2), and
      1alpha,25(OH)(2)D(3), respectively. Method comparisons to 3 other LC-MS/MS
      methods yielded an r(2) value >0.9, an intercept less than the lower limit of
      quantification, and a slope statistically indistinguishable from 1.0.
      CONCLUSIONS: LC-MS/MS can be used to characterize antibody cross-reactivity, a
      conclusion supported by our multiplexed assay for 5 vitamin D metabolites with
      immunoenrichment in a targeted metabolomic assay.

PMID- 22968105
TI  - The evolving threat of influenza viruses of animal origin and the challenges in
      developing appropriate diagnostics.
AB  - BACKGROUND: An H1N1 subtype of swine origin caused the first influenza pandemic
      in this century. This pandemic strain was a reassortant of avian, swine, and
      human influenza viruses. Many diagnostic laboratories were overwhelmed by the
      testing demands related to this pandemic. Nevertheless, there remains the threat
      of other animal influenza viruses, such as highly pathogenic H5N1. As a part of
      pandemic preparedness, it is essential to identify the diagnostic challenges that
      will accompany the next pandemic. CONTENT: We discuss the natural reservoir of
      influenza viruses and the possible role of livestock in the emergence of pandemic
      strains. The current commonly used molecular tests for influenza diagnosis or
      surveillance are also briefly reviewed. Some of these approaches are also used to
      detect animal viruses. Unfortunately, owing to a lack of systematic surveillance
      of animal influenza viruses, established tests may not be able to detect pandemic
      strains that have yet to emerge from the animal reservoir. Thus, multiple
      strategies need to be developed for better identification of influenza viruses.
      In addition, molecular assays for detection of mutations associated with
      antiviral resistance and for viral segment reassortments should also be
      encouraged. SUMMARY: Influenza viruses are highly dynamic viruses. Regular and
      systematic influenza surveillance in both humans and animals is essential to
      provide a more comprehensive picture of the prevalent influenza viruses. To
      better prepare for the next pandemic, we should develop some simple and easy-to
      use tests for characterizing newly emerging influenza viruses.

PMID- 22968106
TI  - Clinical implications of a recent adjustment to the high-sensitivity cardiac
      troponin T assay: user beware.

PMID- 22968107
TI  - Excessive blood pressure elevation upon awakening involves an exaggerated cardiac
      response to slight physical activity:  a possible mechanism underlying the risk
      of 'morning surge'.
AB  - OBJECTIVE: An exaggerated elevation in blood pressure around waking potentially
      increases the risk of cardiovascular events, even in individuals with normal
      blood pressure at other-fold of day. The impact of such a transient blood
      pressure elevation is disproportionate to its short duration, and the reason has
      not been elucidated. We hypothesize that individuals with such a blood pressure
      abnormality receive a cardiovascular overload, even from slight physical
      activities that are frequently undertaken in daily life. METHODS: A total of 16
      patients with essential hypertension (52 +/- 15 years) staying at hospital for
      lifestyle education participated in this study. Morning blood pressure elevation
      was assessed with 24 h ambulatory blood pressure monitoring. Cardiovascular
      responses to unloaded pedaling, including blood pressure changes, were assessed
      in a limited maximum exercise test using an electronically braked bicycle
      ergometer. RESULTS: Changes in the systolic blood pressure caused by unloaded
      pedaling correlated positively with the elevation in systolic blood pressure
      around waking (r = 0.52, P = 0.05). Moreover, waking elevation of the systolic
      blood pressure correlated with changes in all of the following cardiovascular
      variables during unloaded pedaling: heart rate (r = 0.69, P = 0.003), oxygen
      consumption (r = 0.73, P = 0.001), oxygen pulse (r = 0.62, P = 0.001), and rate
      pressure product (r = 0.64, P = 0.008), respectively. CONCLUSION: These
      observations indicate that individuals with prominent blood pressure elevation
      upon awakening also experience cardiovascular overload from slight physical
      activities.

PMID- 22968108
TI  - Validation of the Rossmax S150 wrist blood pressure monitor for home blood
      pressure monitoring according to the European Society of Hypertension
      International Protocol revision 2010.
AB  - OBJECTIVE: The present study aimed to evaluate the accuracy of the automated
      oscillometric wrist blood pressure monitor Rossmax S150 for home blood pressure
      monitoring according to the International Protocol of the European Society of
      Hypertension revision 2010. METHODS: Systolic and diastolic blood pressures were
      sequentially measured in 33 adult Chinese (16 women, mean age of 54 years) using
      a mercury sphygmomanometer (two observers) and the Rossmax S150 device (one
      supervisor). Ninety-nine pairs of comparisons were obtained from 33 participants
      for judgments in two parts with three grading phases. Data analysis was carried
      out using the ESHIP analyzer. RESULTS: The Rossmax S150 device achieved the
      targets in part 1 of the validation study. The number of absolute differences
      between device and observers within 5, 10, and 15 mmHg was 70/99, 90/99, and
      97/99, respectively, for systolic blood pressure, and 84/99, 98/99, and 99/99,
      respectively, for diastolic blood pressure. The device also achieved the criteria
      in part 2 of the validation study. Twenty-six and 29 participants for systolic
      and diastolic blood pressure, respectively, had at least two of the three device
      observers differences within 5 mmHg (required >= 24). Three and two participants
      for systolic and diastolic blood pressure, respectively, had all three device
      observers comparisons greater than 5 mmHg. CONCLUSION: The Rossmax wrist blood
      pressure monitor S150 has passed the requirements of the International Protocol
      revision 2010, and hence can be recommended for home use in adults.

PMID- 22968109
TI  - Validation of the Nihon Kohden PVM-2701/Impulse-1 automated device by both AAMI
      (2002) and ISO standards testing.
AB  - OBJECTIVES: We evaluated a new algorithm, the Nihon Kohden PVM-2701/Impulse-1, in
      an automated sphygmomanometer against the requirements of both the Association
      for the Advancement of Medical Instrumentation (AAMI) SP10 and International
      Standards Organization (ISO) standards. The Impulse-1 algorithm primarily
      utilizes a 1 pulse/step deflation. The advantage of the system is to reduce the
      time of deflation and improve patient comfort. METHODS: We tested 110
      participants (41 children) to fulfill the Standards requirements. We used the
      more up-to-date statistical analyses in the ISO standard. RESULTS: The mean +/-
      SD for method 1 analyses for systolic blood pressure was 0.3 +/- 6.5 mmHg. For
      diastolic blood pressure the value was -0.3 +/- 7.7 mmHg. Method 2 analyses gave
      values of 0.3 +/- 5.2 mmHg for systolic blood pressure and -0.3 +/- 6.7 mmHg for
      diastolic blood pressure. All of the data were within the Standards requirements
      to pass testing. There was no trend for overestimation or underestimation of BP
      at either low or high BP levels. CONCLUSION: The Impulse-1 algorithm passed both
      the AAMI and ISO standards testing in children and adults. The novelties of the 1
      pulse/step deflation algorithm are the significant reduction in deflation time
      and the manufacturer's claim concerning artifact rejection for both dysrhythmia
      and motion.

PMID- 22968110
TI  - Ambulatory blood pressure monitoring in acute stroke:  the importance of time
      rate of blood pressure variation.

PMID- 22968113
TI  - Mammary epithelial-restricted expression of activated c-src rescues the block to
      mammary gland morphogenesis due to the deletion of the C-terminus of Patched-1.
AB  - Mesenchymal dysplasia (mes) mice expressing a C-terminally truncated version of
      the Hedgehog (Hh)-ligand receptor, Patched-1 (Ptch1), exhibit a limited spectrum
      of developmental defects including blocked ductal morphogenesis of the mammary
      gland during puberty. Given that the Hh-ligands can stimulate signalling cascades
      distinct from the canonical pathway involving Smo and the Gli-family proteins and
      that Ptch1 binds to factors harbouring SH3-domains, we determined whether the mes
      mammary gland defect could be rescued by activating non-canonical signalling
      pathways downstream of Ptch1. We demonstrate here that expression of
      constitutively active c-src (c-src(Act)) in mammary epithelial cells overcomes
      the block to mammary epithelial morphogenesis in mes mice. Specifically, MMTV
      directed expression of c-src(Act) rescued blocked ductal morphogenesis in mes
      mice, albeit only after animals were more than 15 weeks of age. The overall
      morphology resembled wild type mice expressing c-src(Act) although 40% of
      mes/MMTV-c-src(Act) mice exhibited terminal end buds at 24 weeks of age. C
      src(Act) restored the proliferative capacity of mes epithelial cells, self
      renewal capacity of mammary progenitor cells and increased the expression of
      Esr1, Ptch1 and Gli1. These data reveal the cooperative interactions between
      signalling cascades involving c-src and Ptch1 and suggest that Hh-signalling may
      be permissive for c-src/Esr1-dependent mammary gland morphogenesis.

PMID- 22968114
TI  - The new standard: single family room design.
AB  - Nurse leaders influence decisions related to single patient rooms or
      multioccupancy room designs. The purpose of this facility design article is to
      expand nurse leaders' knowledge and competency in health facility design enabling
      them to lead design efforts and the transition to new facilities and models of
      care. This article describes the new standard of all-private rooms for adult and
      neonatal ICU care and defines the benefits of the single family room design on
      patients, families, and providers.

PMID- 22968115
TI  - The evolution of a manual revision.
AB  - This month, the director of the Magnet Recognition Program(r) provides an in
      depth overview of the Magnet Recognition Program's Application Manual revision
      process. The history of the 2005 Manual revision, an evidence-based review of the
      literature, and revisions to the 2008 Manual are key elements of this article.

PMID- 22968116
TI  - Graduate practicums in nursing administration programs: current approaches and
      recommendations.

PMID- 22968117
TI  - A strategy to improve nurses speaking up and collaborating for patient safety.

PMID- 22968118
TI  - Nurturing charge nurses for future leadership roles.
AB  - Charge nurses are untapped leadership resources that can be groomed for future
      advanced leadership positions in healthcare organizations. The purpose of this
      study was to understand the development needs for the charge nurse role. This
      study demonstrates they receive little or no training for assuming positions of
      leadership and offers suggestions for enhancement of preparation.

PMID- 22968119
TI  - A leadership challenge: staff nurse perceptions after an organizational
      TeamSTEPPS initiative.
AB  - The purpose of this study was to measure RNs' perceptions of teamwork skills and
      behaviors in their work environment during a multiphase multisite nursing
      organizational teamwork development initiative. Teamwork is essential for patient
      safety in healthcare organizations and nursing teams. Organizational development
      supporting effective teamwork should include a just culture, engaged leadership,
      and teamwork training. A cross-sectional survey study of bedside RNs was
      conducted in one 5-hospital healthcare system after a TeamSTEPPS teamwork
      training initiative. TeamSTEPPS teamwork training related to improved RN
      perceptions of leadership. Initiatives to align the perspectives and teamwork
      efforts of leaders and bedside nurses are indicated and should involve charge
      nurses in the design.

PMID- 22968120
TI  - Congruence of perceptions among nursing leaders and staff regarding missed
      nursing care and teamwork.
AB  - The objective of this study was to test the congruence of the perceptions of unit
      based nurse leaders (managers, advanced practice nurses) and nursing staff
      members (registered nurses, nursing assistants, unit secretaries) in acute care
      hospitals as to the extent and type of missed nursing care and nursing teamwork.
      Based on the leader-member exchange congruence framework (LMX), nursing staff and
      nursing leaders completed the MISSCARE Survey, and a segment of the participants
      completed the Nursing Teamwork Survey. The findings of this study show a lack of
      LMX congruence between leaders and nursing staff members. Nursing staff report
      less missed care and lower teamwork than do leaders, and nursing staff list more
      problems with having adequate material and labor resources than do leaders. LMX
      congruence has been associated with positive organizational outcomes.

PMID- 22968121
TI  - Incorporating quality and safety education into a nursing administration
      curriculum.
AB  - The Quality and Safety Education for Nursing initiative is aimed at developing
      student competences in quality and safety. Because practicing nurses have not
      been exposed to this initiative, nurse leaders must be aware of these
      competencies to develop these competencies in existing staff members. This
      article provides a roadmap to curriculum development in a nursing administration
      graduate program focused on quality and safety.

PMID- 22968122
TI  - The degree of horizontal violence in RNs practicing in New York State.
AB  - This study examined the degree of horizontal violence (HV) among RNs practicing
      in New York State (NYS). The objective was to determine the knowledge of HV and
      the degree of being a victim among practicing RNs. A descriptive survey using
      Briles' Sabotage Savvy Questionnaire, measuring occurrences of HV and nurses'
      knowledge of HV, was conducted among 2659 RNs in NYS hospitals. Findings
      demonstrate a significantly greater (P < .05) degree of HV in union versus
      nonunion cultures and less HV in Magnet(r) organizations. Gender and RN education
      significantly impacted HV. Developing organizational, leadership, and individual
      interventions to address HV helps create a culture of safety.

PMID- 22968124
TI  - Sedentary behavior: understanding and influencing adults' prolonged sitting time.
AB  - Too much sitting is now understood to be a health risk that is additional to, and
      distinct from, too little exercise. There is a rapidly-accumulating evidence on
      relationships of prolonged sedentary time and patterns of sedentary time with
      cardio-metabolic risk biomarkers and health outcomes. There is, however, the need
      to gather dose-response evidence and develop a broader understanding of the set
      of mechanisms linking sedentary behavior to health outcomes. In addition to the
      further understanding of the associated health risks, there is a new health
      behavior, and epidemiological and experimental research agenda to be pursued,
      which include measurement studies; understanding the relevant determinants
      particularly environmental determinants of sedentary behavior; and, developing
      effective interventions. A broad-based body of evidence is needed to inform the
      research-translation agenda-identifying and developing the future public health
      initiatives, environmental and policy changes and clinical guidelines that may be
      required.

PMID- 22968125
TI  - Electronic structure and chemical bonding of a graphene oxide-sulfur
      nanocomposite for use in superior performance lithium-sulfur cells.
AB  - We have investigated the chemical bonding and electronic structure of a graphene
      oxide-sulfur (GO-S) nanocomposite by X-ray Photoelectron Spectroscopy (XPS), Near
      edge X-ray Absorption Fine Structure (NEXAFS), and X-ray Emission Spectroscopy
      (XES). The nanocomposite, synthesized by a chemical reaction-deposition approach
      followed by low temperature thermal treatment, is composed of a thin and uniform
      sulfur film anchored on a graphene oxide (GO) sheet. The GO is partially reduced
      during the chemical synthesis process, resulting in the appearance of a C-H bond
      and an increase in the ordering of GO sheets. The moderate chemical interactions
      between sulfur and GO can preserve the intrinsic electronic structure of GO, and
      on the other hand, immobilize the sulfur on the GO sheets, which should be
      responsible for the excellent electrochemical performance of the lithium-sulfur
      cells by using the GO-S nanocomposite as the cathode material.

PMID- 22968126
TI  - Genome-wide biochemical analysis of Arabidopsis protein phosphatase using a wheat
      cell-free system.
AB  - Plant genome possesses over 100 protein phosphatase (PPase) genes that are key
      regulators of signal transduction via phosphorylation/dephosphorylation event.
      Here we report a comprehensive functional analysis of protein serine/threonine,
      dual-specificity and tyrosine phosphatases using recombinant PPases produced by
      wheat cell-free protein synthesis system. Eighty-two recombinant PPases were
      successfully produced using Arabidopsis full-length cDNA as templates. In vitro
      PPase assay was performed using phosphorylated myelin basic protein as substrate.
      Among the AtPPases examined, 26 serine/threonine, three dual-specificity and one
      tyrosine PPases exhibited catalytic activity, including 20 serine/threonine and
      one dual-specificity PPases that showed in vitro activities for the first time.
      Our study demonstrates genome-wide biochemical analysis of AtPPases using wheat
      cell-free system, and provides new information and insights on enzyme activities.

PMID- 22968127
TI  - The MeTeOR trial (Meniscal Tear in Osteoarthritis Research): rationale and design
      features.
AB  - This paper presents the rationale and design features of the MeTeOR Trial
      (Meniscal Tear in Osteoarthritis Research; Clinical Trials.gov NCT00597012).
      MeTeOR is an NIH-funded seven-center prospective randomized controlled trial
      (RCT) designed to establish the efficacy of arthroscopic partial meniscectomy
      combined with a standardized physical therapy program as compared with a
      standardized physical therapy program alone in patients with a symptomatic
      meniscal tear in the setting of mild to moderate knee osteoarthritic change (OA).
      The design and execution of a trial that compares surgery with a nonoperative
      treatment strategy presents distinctive challenges. The goal of this paper is to
      provide the clinical rationale for MeTeOR and to highlight salient design
      features, with particular attention to those that present clinical and
      methodologic challenges.

PMID- 22968128
TI  - Role of P2X7 receptor-mediated IL-18/IL-18R signaling in morphine tolerance:
      multiple glial-neuronal dialogues in the rat spinal cord.
AB  - The glial function in morphine tolerance has been explored, but its mechanisms
      remain unclear. Our previous study has showed that microglia-expressed P2X7
      receptors (P2X7R) contribute to the induction of tolerance to morphine analgesia
      in rats. This study further explored the potential downstream mechanisms of P2X7R
      underlying morphine tolerance. The results revealed that the blockade of P2X7
      receptor by P2X7R antagonist or targeting small interfering RNA (siRNA) reduced
      tolerance to morphine analgesia in the pain behavioral test and spinal
      extracellular recordings in vivo and whole-cell recording of the spinal cord
      slice in vitro. Chronic morphine treatment induced an increase in the expression
      of interleukin (IL)-18 by microglia, IL-18 receptor (IL-18R) by astrocytes, and
      protein kinase Cgamma (PKCgamma) by neurons in the spinal dorsal horn,
      respectively, which was blocked by a P2X7R antagonist or targeting siRNA. Chronic
      morphine treatment also induced an increased release of D-serine from the spinal
      astrocytes. Further, both D-amino acid oxygenase (DAAO), a degrading enzyme of D
      serine, and bisindolylmaleimide alpha (BIM), a PKC inhibitor, attenuated morphine
      tolerance. The present study demonstrated a spinal mechanism underlying morphine
      tolerance, in which chronic morphine triggered multiple dialogues between glial
      and neuronal cells in the spinal cord via a cascade involving a P2X7R-IL-18-D
      serine-N-methyl-D-aspartate receptor (NMDAR)-PKCgamma-mediated signaling pathway.
      PERSPECTIVE: The present study shows that glia-neuron interaction via a cascade
      (P2X7R-IL-18-D-serine-NMDAR-PKCgamma) in the spinal cord plays an important role
      in morphine tolerance. This article may represent potential new therapeutic
      targets for preventing morphine analgesic tolerance in clinical management of
      chronic pain.

PMID- 22968129
TI  - Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and
      dissections and patent ductus arteriosus.
AB  - Thoracic aortic aneurysms and dissections (TAAD) is a serious condition with high
      morbidity and mortality. It is estimated that 20% of non-syndromic TAAD cases are
      inherited in an autosomal-dominant pattern with variable expression and reduced
      penetrance. Mutations in myosin heavy chain 11 (MYH11), one of several identified
      TAAD genes, were shown to simultaneously cause TAAD and patent ductus arteriosus
      (PDA). We identified two large Dutch families with TAAD/PDA and detected two
      different novel heterozygote MYH11 variants in the probands. These variants, a
      heterozygote missense variant and a heterozygote in-frame deletion, were
      predicted to have damaging effects on protein structure and function. However,
      these novel alterations did not segregate with the TAAD/PDA in 3 out of 11 cases
      in family TAAD01 and in 2 out of 6 cases of family TAAD02. No mutation was
      detected in other known TAAD genes. Thus, it is expected that within these
      families other genetic factors contribute to the disease either by themselves or
      by interacting with the MYH11 variants. Such an oligogenic model for TAAD would
      explain the variable onset and progression of the disorder and its reduced
      penetrance in general. We conclude that in familial TAAD/PDA with an MYH11
      variant in the index case caution should be exercised upon counseling family
      members. Specialized surveillance should still be offered to the non-carriers to
      prevent catastrophic aortic dissections or ruptures. Furthermore, our study
      underscores that segregation analysis remains very important in clinical
      genetics. Prediction programs and mutation evaluation algorithms need to be
      interpreted with caution.

PMID- 22968130
TI  - Next-generation sequencing (NGS) as a diagnostic tool for retinal degeneration
      reveals a much higher detection rate in early-onset disease.
AB  - Inherited retinal degeneration (IRD) is a common cause of visual impairment
      (prevalence ~1/3500). There is considerable phenotype and genotype heterogeneity,
      making a specific diagnosis very difficult without molecular testing. We
      investigated targeted capture combined with next-generation sequencing using
      Nimblegen 12plex arrays and the Roche 454 sequencing platform to explore its
      potential for clinical diagnostics in two common types of IRD, retinitis
      pigmentosa and cone-rod dystrophy. 50 patients (36 unknowns and 14 positive
      controls) were screened, and pathogenic mutations were identified in 25% of
      patients in the unknown, with 53% in the early-onset cases. All patients with new
      mutations detected had an age of onset <21 years and 44% had a family history.
      Thirty-one percent of mutations detected were novel. A de novo mutation in
      rhodopsin was identified in one early-onset case without a family history.
      Bioinformatic pipelines were developed to identify likely pathogenic mutations
      and stringent criteria were used for assignment of pathogenicity. Analysis of
      sequencing metrics revealed significant variability in capture efficiency and
      depth of coverage. We conclude that targeted capture and next-generation
      sequencing are likely to be very useful in a diagnostic setting, but patients
      with earlier onset of disease are more likely to benefit from using this
      strategy. The mutation-detection rate suggests that many patients are likely to
      have mutations in novel genes.

PMID- 22968131
TI  - Contemporary paternal genetic landscape of Polish and German populations: from
      early medieval Slavic expansion to post-World War II resettlements.
AB  - Homogeneous Proto-Slavic genetic substrate and/or extensive mixing after World
      War II were suggested to explain homogeneity of contemporary Polish paternal
      lineages. Alternatively, Polish local populations might have displayed pre-war
      genetic heterogeneity owing to genetic drift and/or gene flow with neighbouring
      populations. Although sharp genetic discontinuity along the political border
      between Poland and Germany indisputably results from war-mediated resettlements
      and homogenisation, it remained unknown whether Y-chromosomal diversity in
      ethnically/linguistically defined populations was clinal or discontinuous before
      the war. In order to answer these questions and elucidate early Slavic
      migrations, 1156 individuals from several Slavic and German populations were
      analysed, including Polish pre-war regional populations and an autochthonous
      Slavic population from Germany. Y chromosomes were assigned to 39 haplogroups and
      genotyped for 19 STRs. Genetic distances revealed similar degree of
      differentiation of Slavic-speaking pre-war populations from German populations
      irrespective of duration and intensity of contacts with German speakers.
      Admixture estimates showed minor Slavic paternal ancestry (~20%) in modern
      eastern Germans and hardly detectable German paternal ancestry in Slavs
      neighbouring German populations for centuries. BATWING analysis of isolated
      Slavic populations revealed that their divergence was preceded by rapid
      demographic growth, undermining theory that Slavic expansion was primarily
      linguistic rather than population spread. Polish pre-war regional populations
      showed within-group heterogeneity and lower STR variation within R-M17 subclades
      compared with modern populations, which might have been homogenised by war
      resettlements. Our results suggest that genetic studies on early human history in
      the Vistula and Oder basins should rely on reconstructed pre-war rather than
      modern populations.

PMID- 22968132
TI  - 14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett
      syndrome-like phenotype.
AB  - Rett syndrome is a clinically defined neurodevelopmental disorder almost
      exclusively affecting females. Usually sporadic, Rett syndrome is caused by
      mutations in the X-linked MECP2 gene in ~90-95% of classic cases and 40-60% of
      individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been
      associated with the early-onset seizure variant of Rett syndrome and mutations in
      FOXG1 have been associated with the congenital Rett syndrome variant. We report
      the clinical features and array CGH findings of three atypical Rett syndrome
      patients who had severe intellectual impairment, early-onset developmental delay,
      postnatal microcephaly and hypotonia. In addition, the females had a seizure
      disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were
      found to have an interstitial deletion of 14q12. The deleted region in common
      included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis
      suggested a decrease in FOXG1 levels in two of the patients. Screening of 32
      atypical Rett syndrome patients did not identify any pathogenic mutations in the
      PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1
      (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett
      syndrome variant. There is phenotypic overlap between congenital Rett syndrome
      variants with FOXG1 mutations and the clinical presentation of our three patients
      with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that
      the primary defect in these patients is misregulation of the FOXG1 gene rather
      than a primary abnormality of PRKD1.

PMID- 22968133
TI  - Public support and consent preference for biomedical research and biobanking in
      Jordan.
AB  - The success of any biobank depends on a number of factors including public's view
      of research and the extent to which it is willing to participate in research. As
      a prototype of surrounding countries, public interest in research and biobanking
      in addition to the influence and type of informed consent for biobanking were
      investigated in Jordan. Data were collected as part of a national survey of 3196
      individuals representing the Jordanian population. The majority of respondents
      (88.6%) had a positive perception of the level of research in Jordan and they
      overwhelmingly (98.2%) agreed to the concept of investing as a country in
      research. When respondents were asked if the presence of an informed consent
      would influence their decision to participate in biobanking, more individuals
      (19.8%) considered having an informed consent mechanism as a positive factor than
      those who considered it to have negative connotations (13.1%). However, a
      substantial portion (65%) did not feel it affected their decision. The majority
      of survey participants (64%) expressed willingness to participate in biobanking
      and over 90% of them preferred an opt-in consent form whether general (75.2%) or
      specific for disease or treatment (16.9%). These results indicate a promising
      ground for research and biobanking in Jordan. Educational programs or mass
      awareness campaigns to promote participation in biobanking and increase awareness
      about informed consent and individual rights in research will benefit both the
      scientific community as well as the public.

PMID- 22968134
TI  - Clinical utility gene card for: pseudohypoparathyroidism.

PMID- 22968135
TI  - Low-density lipoprotein receptor mutations generate synthetic genome-wide
      associations.
AB  - Genome-wide association (GWA) studies have discovered multiple common genetic
      risk variants related to common diseases. It has been proposed that a number of
      these signals of common polymorphisms are based on synthetic associations that
      are generated by rare causative variants. We investigated if mutations in the low
      density lipoprotein receptor (LDLR) gene causing familial hypercholesterolemia
      (FH, OMIM #143890) produce such signals. We genotyped 480 254 polymorphisms in
      464 FH patients and in 5945 subjects from the general population. A total of 28
      polymorphisms located up to 2.4 Mb from the LDLR gene were genome-wide
      significantly associated with FH (P<10(-8)). We replicated the 10 top signals in
      2189 patients with a clinical diagnosis of FH and in 2157 subjects of a second
      sample of the general population (P<0.000087). Our findings confirm that rare
      variants are able to cause synthetic genome-wide significant associations, and
      that they exert this effect at relatively large distances from the causal
      mutation.

PMID- 22968137
TI  - Fuzzy Synchronization Likelihood-wavelet methodology for diagnosis of autism
      spectrum disorder.
AB  - This paper presents a methodology for investigation of functional connectivity in
      patients with autism spectrum disorder (ASD) using Fuzzy Synchronization
      Likelihood (Fuzzy SL). Fuzzy SLs between and within brain regions are calculated
      in all EEG sub-bands produced by the wavelet decomposition as well as in the full
      band EEG. Then, discriminative Fuzzy SLs between and within different regions and
      different EEG sub-bands or full-band EEG for distinguishing autistic children
      from healthy control children are determined based on Analysis of Variation
      (ANOVA). Finally, the selected features are used as input to an Enhanced
      Probabilistic Neural Network classifier to make an accurate diagnosis of ASD
      based on the detected differences in the regional functional connectivity of
      autistic and healthy EEGs. The methodology is validated using EEG data obtained
      from 9 autistic and 9 healthy children. The ANOVA test showed high ability of the
      regional Fuzzy SLs in low frequency bands, delta and theta, as well as alpha band
      for discriminating the two groups. A high classification accuracy of 95.5% was
      achieved for distinguishing autistic EEGs from healthy EEGs. It is concluded that
      the methodology presented in this paper can be used as an effective tool for
      diagnosis of the autism. Further, the regional Fuzzy SLs discovered in this
      research can be used as reliable markers in neurofeedback treatments to improve
      neuronal plasticity and connectivity in autistic patients.

PMID- 22968136
TI  - Expanding the MTM1 mutational spectrum: novel variants including the first multi
      exonic duplication and development of a locus-specific database.
AB  - Myotubular myopathy (MIM#310400), the X-linked form of Centronuclear myopathy
      (CNM) is mainly characterized by neonatal hypotonia and inability to maintain
      unassisted respiration. The MTM1 gene, responsible for this disease, encodes
      myotubularin - a lipidic phosphatase involved in vesicle trafficking regulation
      and maturation. Recently, it was shown that myotubularin interacts with desmin,
      being a major regulator of intermediate filaments. We report the development of a
      locus-specific database for MTM1 using the Leiden Open Variation database
      software (http://www.lovd.nl/MTM1), with data collated for 474 mutations
      identified in 472 patients (by June 2012). Among the entries are a total of 25
      new mutations, including a large deletion encompassing introns 2-15. During
      database implementation it was noticed that no large duplications had been
      reported. We tested a group of eight uncharacterized CNM patients for this
      specific type of mutation, by multiple ligation-dependent probe amplification
      (MLPA) analysis. A large duplication spanning exons 1-5 was identified in a boy
      with a mild phenotype, with results pointing toward possible somatic mosaicism.
      Further characterization revealed that this duplication causes an in-frame
      deletion at the mRNA level (r.343_444del). Results obtained with a next
      generation sequencing approach suggested that the duplication extends into the
      neighboring MAMLD1 gene and subsequent cDNA analysis detected the presence of a
      MTM1/MAMLD1 fusion transcript. A complex rearrangement involving the duplication
      of exon 10 has since been reported, with detection also enabled by MLPA analysis.
      It is thus conceivable that large duplications in MTM1 may account for a number
      of CNM cases that have remained genetically unresolved.

PMID- 22968138
TI  - LV wall segmentation using the variational level set method (LSM) with additional
      shape constraint for oedema quantification.
AB  - In this paper an automatic algorithm for the left ventricle (LV) wall
      segmentation and oedema quantification from T2-weighted cardiac magnetic
      resonance (CMR) images is presented. The extent of myocardial oedema delineates
      the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can
      be used to estimate the amount of salvageable myocardial post-MI, oedema imaging
      has potential clinical utility in the management of acute MI patients. This paper
      presents a new scheme based on the variational level set method (LSM) with
      additional shape constraint for the segmentation of T2-weighted CMR image. In our
      approach, shape information of the myocardial wall is utilized to introduce a
      shape feature of the myocardial wall into the variational level set formulation.
      The performance of the method is tested using real CMR images (12 patients) and
      the results of the automatic system are compared to manual segmentation. The mean
      perpendicular distances between the automatic and manual LV wall boundaries are
      in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is
      no consistent bias as a function of LV wall area, with a mean bias of -121 mm(2)
      between individual investigator one (IV1) and LSM, and -122 mm(2) between
      individual investigator two (IV2) and LSM when compared to two investigators.
      Furthermore, the oedema quantification demonstrates good correlation when
      compared to an expert with an average error of 9.3% for 69 slices of short axis
      CMR image from 12 patients.

PMID- 22968139
TI  - Misoprostol for preventing and treating postpartum hemorrhage in the community: a
      closer look at the evidence.
AB  - The lack of clear interpretation of clinical and operational evidence on
      misoprostol use for postpartum hemorrhage (PPH) in the community may jeopardize
      the realization of its full potential for improving women's survival. This paper
      highlights the usefulness of misoprostol in addressing PPH in the community
      within the limits of available research evidence. There is now substantial
      evidence to support the beneficial effects of 600 MUg of oral misoprostol for PPH
      prevention in the community, with a trend toward better protection against severe
      PPH morbidity, and particularly when administered by less skilled or lay
      caregivers. Although there is tangible evidence to show that 800 MUg of
      sublingual misoprostol has important benefits for PPH treatment where there is no
      access to oxytocin, there is presently no direct evidence to indicate that less
      skilled or lay caregivers can safely use it to treat PPH in the community.
      Operational research evidence indicates that advance community distribution of
      misoprostol to pregnant women for postpartum self-use is a feasible strategy to
      ensure availability of the drug at the time of birth. The evidence is, however,
      limited by its quality to establish whether the benefits of such a strategy truly
      outweigh the potential harms. It is time for the international community to focus
      on improving PPH-related outcomes by scaling up what is currently guided by hard
      evidence and join forces to address unanswered questions through high-quality
      research.

PMID- 22968140
TI  - Morphologic changes in the placentas of HIV-positive women and their association
      with degree of immune suppression.
AB  - OBJECTIVE: To provide baseline information regarding a possible association
      between specific histopathologic features of the placentas of HIV-positive women
      and the degree of immune suppression. METHODS: A prospective single-blinded
      laboratory-based pilot study was conducted at Tygerberg Hospital, South Africa.
      The macroscopic and microscopic features of placentas from HIV-positive (n=91)
      and HIV-negative women (n=89) were compared and recorded using a standard
      template. Investigators were blinded to the participants' HIV status and CD4
      positive cell count. RESULTS: Placentas from the HIV-positive group were
      characterized by decreased weight and increased number of marginal infarcts
      relative to the HIV-negative group. The most important microscopic finding was
      the increased presence of villitis of unknown etiology (VUE) among the group of
      untreated HIV-positive women with CD4 cell counts of 200 cells/mm(3) or below.
      CONCLUSION: Both macroscopic and microscopic differences relating to the degree
      of immune suppression were identified, which seemingly contradicts previous
      reports. Larger studies are warranted to define the function of antiretroviral
      therapy and VUE in the mechanism of mother-to-fetus transmission of HIV.
      Furthermore, the potential role of VUE in the pathophysiology of the compromised
      immune response observed among HIV-exposed but uninfected infants should be
      investigated.

PMID- 22968141
TI  - Pseudoaneurysm of the internal iliac artery following vaginal hysterectomy.

PMID- 22968142
TI  - Rasch analysis reveals problems with multiplicative scoring in the macular
      disease quality of life questionnaire.
AB  - PURPOSE: To evaluate validity and psychometric characteristics of the Macular
      Disease Quality of Life questionnaire (MacDQoL), a multiplicative rating scale
      designed to measure vision-related quality of life (VRQoL) in macular diseases
      and age-related macular degeneration (AMD). DESIGN: Cross-sectional study.
      PARTICIPANTS: We included 108 patients with neovascular AMD at baseline before
      ranibizumab treatment. METHODS: The psychometric properties of the MacDQoL were
      assessed using Rasch analysis, exploring key indices such as response category
      functioning, instrument unidimensionality, discriminant ability, and targeting of
      item difficulty to patient ability. MAIN OUTCOME MEASURES: Measurement
      characteristics of the MacDQoL. RESULTS: In the MacDQoL's native form, the
      majority of response categories were underutilized and thresholds disordered.
      This could not be remedied without eliminating the importance ratings owing to
      the ambiguous nature of the response categories. Scaling problems were resolved
      by using the impairment rating scale only and collapsing response categories to
      4. However, the MacDQoL was multidimensional, necessitating the omission of a
      number of items and splitting it into an activity limitation and mobility and a
      socioemotional well-being scale. This improved the psychometric parameters of the
      revised MacDQoL, although no correlation with clinical measures such as visual
      acuity was found. CONCLUSIONS: The multiplicative rating scale of the MacDQoL is
      flawed and does not provide scientific measurement of VRQoL. Measurement can be
      restored with a series of revisions to the instrument. This study reinforces the
      importance of considering rating scale design when choosing patient reported
      outcomes instruments for healthcare research.

PMID- 22968143
TI  - A highly sensitive method for molecular diagnosis of fungal keratitis: a dot
      hybridization assay.
AB  - PURPOSE: Fungal keratitis (FK) is an important cause of ocular morbidity,
      especially for people living in the agricultural communities of the developing
      world. Current diagnostic methods may lack sensitivity (direct microscopy) or are
      time consuming (culture). The aim of this study was to develop a dot
      hybridization assay for sensitive and rapid diagnosis of FK. DESIGN: Evaluation
      of diagnostic test or technology. PARTICIPANTS AND CONTROLS: Fifty corneal
      scrapes (49 patients) from consecutive cases of clinically suspected microbial
      keratitis were analyzed prospectively. METHODS: Molecular detection of fungi in
      the scrapes was performed by amplification of the internal transcribed spacer
      region (ITS) that contained the target gene (5.8S rRNA gene) by polymerase chain
      reaction (PCR), followed by hybridization of the PCR product to a fungus-specific
      oligonucleotide probe immobilized on a nylon membrane. The results were compared
      with those obtained by gram-stain microscopy, culture, and gel electrophoresis of
      the PCR products. Discrepant results were resolved by cloning and resequencing of
      the amplified ITS fragments. MAIN OUTCOME MEASURES: Performance of the dot
      hybridization assay, including sensitivity, specificity, and positive and
      negative predictive values, was evaluated. RESULTS: Ten scrapes demonstrated
      positive results by both the dot hybridization assay and culture. However, 11
      scrapes demonstrated positive results by the dot hybridization assay, but
      demonstrated negative results by culture, and 10 of the 11 samples were
      considered to be positive for FK by cloning and resequencing of the amplified ITS
      fragment and by a pathologic examination or clinical course review. The
      sensitivities for diagnosis of FK by the dot hybridization assay and culture were
      100% and 50%, respectively, whereas the specificities were 96.7% and 100%,
      respectively. CONCLUSIONS: The dot hybridization assay is a highly sensitive and
      specific diagnostic tool for FK. The method provides a much higher sensitivity
      than that of culture (100% vs. 50%; P<0.001). The hybridization procedure can be
      finished within a working day. It is expected that the method can have an impact
      on the diagnosis and treatment of FK in the future. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 22968144
TI  - Determinants and two-year change in anterior chamber angle width in a Chinese
      population.
AB  - OBJECTIVE: To study the population distribution and longitudinal changes in
      anterior chamber angle width and its determinants among Chinese adults. DESIGN:
      Prospective cohort, population-based study. PARTICIPANTS: Persons aged 35 years
      or more residing in Guangzhou, China, who had not previously undergone incisional
      or laser eye surgery. METHODS: In December 2008 and December 2010, all subjects
      underwent automated keratometry, and a random 50% sample had anterior segment
      optical coherence tomography with measurement of angle-opening distance at 500
      MUm (AOD500), angle recess area (ARA), iris thickness at 750 MUm (IT750), iris
      curvature, pupil diameter, corneal thickness, anterior chamber width (ACW), lens
      vault (LV), and lens thickness (LT) and measurement of axial length (AL) and
      anterior chamber depth (ACD) by partial coherence laser interferometry. MAIN
      OUTCOME MEASURES: Baseline and 2-year change in AOD500 and ARA in the right eye.
      RESULTS: A total of 745 subjects were present for full biometric testing in both
      2008 and 2010 (mean age at baseline, 52.2 years; standard deviation [SD], 11.5
      years; 53.7% were female). Test completion rates in 2010 varied from 77.3%
      (AOD500: 576/745) to 100% (AL). Mean AOD500 decreased from 0.25 mm (SD, 0.13 mm)
      in 2008 to 0.21 mm (SD, 13 mm) in 2010 (difference, -0.04; 95% confidence
      interval [CI], -0.05 to -0.03). The ARA decreased from 21.5 +/- 3.73 10(-2) mm(2)
      to 21.0 +/- 3.64 10(-2) mm(2) (difference, -0.46; 95% CI, -0.52 to -0.41). The
      decrease in both was most pronounced among younger subjects and those with
      baseline AOD500 in the widest quartile at baseline. The following baseline
      variables were significantly associated with a greater 2-year decrease in both
      AOD500 and ARA: deeper ACD, steeper iris curvature, smaller LV, greater ARA, and
      greater AOD500. By using simple regression models, we could explain 52% to 58%
      and 93% of variation in baseline AOD500 and ARA, respectively, but only 27% and
      16% of variation in 2-year change in AOD500 and ARA, respectively. CONCLUSIONS:
      Younger persons and those with the least crowded anterior chambers at baseline
      have the largest 2-year decreases in AOD500 and ARA. The ability to predict
      change in angle width based on demographic and biometric factors is relatively
      poor, which may have implications for screening. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 22968146
TI  - Metformin affects the circadian clock and metabolic rhythms in a tissue-specific
      manner.
AB  - Metformin is a commonly-used treatment for type 2 diabetes, whose mechanism of
      action has been linked, in part, to activation of AMP-activated protein kinase
      (AMPK). However, little is known regarding its effect on circadian rhythms. Our
      aim was to evaluate the effect of metformin administration on metabolism,
      locomotor activity and circadian rhythms. We tested the effect of metformin
      treatment in the liver and muscle of young lean, healthy mice, as obesity and
      diabetes disrupt circadian rhythms. Metformin led to increased leptin and
      decreased glucagon levels. The effect of metformin on liver and muscle metabolism
      was similar leading to AMPK activation either by liver kinase B1 (LKB1) and/or
      other kinases in the muscle. AMPK activation resulted in the inhibition of acetyl
      CoA carboxylase (ACC), the rate limiting enzyme in fatty acid synthesis.
      Metformin also led to the activation of liver casein kinase I alpha (CKIalpha)
      and muscle CKIepsilon, known modulators of the positive loop of the circadian
      clock. This effect was mainly of phase advances in the liver and phase delays in
      the muscle in clock and metabolic genes and/or protein expression. In conclusion,
      our results demonstrate the differential effects of metformin in the liver and
      muscle and the critical role the circadian clock has in orchestrating metabolic
      processes.

PMID- 22968145
TI  - Spectral-domain optical coherence tomography characteristics of intermediate age
      related macular degeneration.
AB  - PURPOSE: Describe qualitative spectral-domain optical coherence tomography (SD
      OCT) characteristics of eyes classified as intermediate age-related macular
      degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2)
      color fundus photography (CFP) grading. DESIGN: Prospective cross-sectional
      study. PARTICIPANTS: We included 345 AREDS2 participants from 4 study centers and
      122 control participants who lack CFP features of intermediate AMD. METHODS: Both
      eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded
      for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In
      all, 314 AREDS2 participants with >=1 category-3 AMD eye and all controls each
      had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test
      reproducibility. MAIN OUTCOME MEASURES: We assessed SD-OCT characteristics at
      baseline. RESULTS: In 98% of AMD eyes, SD-OCT grading of all characteristics was
      successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE)
      atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or
      under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics
      of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD
      OCT. Vision loss was not correlated with foveal drusen alone, but with foveal
      drusen that were associated with other foveal pathology and with overlying focal
      hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper-
      or hyporeflectivity of drusen were also associated with RPE atrophy. CONCLUSIONS:
      Macular pathologies in AMD can be qualitatively and reproducibly evaluated with
      SD-OCT, identifying pathologic features that are associated with vision loss, RPE
      atrophy, and even possibly the presence of advanced AMD not apparent on CFP.
      Qualitative and detailed SD-OCT analysis can contribute to the anatomic
      characterization of AMD in clinical studies of vision loss and disease
      progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be
      found after the references.

PMID- 22968150
TI  - Axon growth: Separating growth from regrowth.

PMID- 22968147
TI  - Activation of SIRT1 protects pancreatic beta-cells against palmitate-induced
      dysfunction.
AB  - Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone
      deacetylase, is an important regulator of energy homeostasis in response to
      nutrient availability. In pancreatic beta-cells, SIRT1 has been shown to up
      regulate insulin secretion in response to glucose stimulation. However, the
      potential roles of SIRT1 in islet beta-cells against lipotoxicity remain poorly
      understood. Here, we demonstrated that SIRT1 mRNA and protein expressions were
      markedly reduced in the islets isolated from rats infused with 20% Intralipid for
      24h. Long-term exposure to 0.4mmol/L palmitate also decreased SIRT1 expression in
      cultured INS-1 cells and isolated rat islets, which was prevented by 10MUmol/L
      resveratrol, a SIRT1 agonist. In addition, resveratrol improved glucose
      stimulated insulin secretion decreased by palmitate, which was abrogated by
      EX527, a specific SIRT1 inhibitor. Furthermore, inhibition of SIRT1 activity by
      EX527 or a knockdown of SIRT1 suppressed insulin promoter activity, along with
      decreased insulin, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A
      (MafA), and NK6 homeodomain 1 (NKX6.1) mRNA expressions. Activation of SIRT1 by
      resveratrol or overexpression of SIRT1 antagonized palmitate-inhibited insulin
      transcriptional activity. SIRT1 overexpression exerted an additive effect on
      pancreatic and duodenal homeobox 1 (PDX1)-stimulated insulin promoter activity
      and abolished forkhead box O1 protein (FOXO1)-decreased insulin transcriptional
      activity. Resveratrol reversed FOXO1 nuclear translocation induced by palmitate.
      Our findings indicate that SIRT1 protects against palmitate-induced beta-cell
      dysfunction.

PMID- 22968152
TI  - Attention: The focus of attention.

PMID- 22968155
TI  - A general intramolecular Friedel-Crafts approach to functionalized pyrrolo[3,2,1
      ij]quinolin-4-ones.
AB  - An indium(III)-catalyzed intramolecular Friedel-Crafts annulation for the
      efficient synthesis of pyrrolo[3,2,1-ij]quinolin-4-ones is described. The
      products are formed in good to excellent yields (51-97%) with
      diastereoselectivities up to >99 : 1 dr.

PMID- 22968156
TI  - The relationship between ACL injuries and physical fitness in young competitive
      ski racers: a 10-year longitudinal study.
AB  - BACKGROUND: Epidemiological studies have shown a high incidence of anterior
      cruciate ligament (ACL) injuries among competitive alpine skiers. Little is known
      regarding modifiable risk factors in young skiers. There are still uncertainties
      in gender-related risk factors. OBJECTIVE: The purpose of this study was to
      determine the relationship between ACL injuries and internal risk factors.
      METHODS: Retrospective data analyses were performed based on a group of 175
      female and 195 male alpine ski racers between the ages of 14 and 19 years. The
      athletes underwent physical testing annually from 1996 to 2006. Z score
      transformations normalised the age groups. Multivariate binary logistic
      regressions were calculated for men and women separately to detect significant
      predictors of ACL ruptures. t Tests were computed to reveal the differences in
      test scores between injured and non-injured athletes. RESULTS: A total of 57
      (15%) ACL injuries occurred. The female-male risk ratio (RR) was higher in
      females (2.3, 95% CI 1.3 to 4.2). Z scores for relative leg force, ratio of
      absolute core flexion to extension force, relative core strength and reactive
      strength index were predictive variables for men. Z scores of all of these
      predictive variables except relative leg force were higher in the non-injured
      group. The ratios of absolute flexion to extension force and absolute core
      strength were predictive covariates for women. Z scores for absolute core
      strength were higher in the non-injured group. CONCLUSIONS: The risk of ACL
      injury was greater in female athletes. The findings suggest that core strength is
      a predominant critical factor for ACL injuries in young ski racers.

PMID- 22968153
TI  - Mind-altering microorganisms: the impact of the gut microbiota on brain and
      behaviour.
AB  - Recent years have witnessed the rise of the gut microbiota as a major topic of
      research interest in biology. Studies are revealing how variations and changes in
      the composition of the gut microbiota influence normal physiology and contribute
      to diseases ranging from inflammation to obesity. Accumulating data now indicate
      that the gut microbiota also communicates with the CNS--possibly through neural,
      endocrine and immune pathways--and thereby influences brain function and
      behaviour. Studies in germ-free animals and in animals exposed to pathogenic
      bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for
      the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus,
      the emerging concept of a microbiota-gut-brain axis suggests that modulation of
      the gut microbiota may be a tractable strategy for developing novel therapeutics
      for complex CNS disorders.

PMID- 22968157
TI  - HEMA inhibits interfacial nano-layering of the functional monomer MDP.
AB  - Previous research showed that the functional monomer 10-methacryloxydecyl
      dihydrogen phosphate (MDP) ionically bonds to hydroxyapatite (HAp) and forms a
      nano-layered structure at the interface with HAp-based substrates. Such
      hydrophobic nano-layering is considered to contribute to the long-term durability
      of the bond to tooth tissue. However, dental adhesives are complex mixtures
      usually containing different monomers. This study investigated the effect of the
      monomer 2-hydroxyethylmethacrylate (HEMA) on the chemical interaction of MDP with
      HAp by x-ray diffraction (XRD), nuclear magnetic resonance (NMR), and quartz
      crystal microbalance (QCM). We examined the chemical interaction of 5
      experimental MDP solutions with increasing concentrations of HEMA. XRD revealed
      that addition of HEMA inhibits nano-layering at the interface, while NMR
      confirmed that MDP remained adsorbed onto the HAp surface. QCM confirmed this
      adsorption of MDP to HAp, as well as revealed that the demineralization rate of
      HAp by MDP was reduced by HEMA. It was concluded that even though the adsorption
      of MDP to HAp was not hindered, addition of HEMA inhibited interfacial nano
      layering. Potential consequences with regard to bond durability necessitate
      further research.

PMID- 22968158
TI  - Evolutionary analysis suggests that AMTN is enamel-specific and a candidate for
      AI.
AB  - Molecular evolutionary analysis is an efficient method to predict and/or validate
      amino acid substitutions that could lead to a genetic disease and to highlight
      residues and motifs that could play an important role in the protein structure
      and/or function. We have applied such analysis to amelotin (AMTN), a recently
      identified enamel protein in the rat, mouse, and humans. An in silico search for
      AMTN provided 42 new mammalian sequences that were added to the 3 published
      sequences with which we performed the analysis using a dataset representative of
      all lineages (circa 220 million years of evolution), including 2 enamel-less
      species, sloth and armadillo. During evolution, of the 209 residues of human
      AMTN, 17 were unchanged and 34 had conserved their chemical properties.
      Substituting these important residues could lead to amelogenesis imperfecta (AI).
      Also, AMTN possesses a well-conserved signal peptide, 2 conserved motifs whose
      function is certainly important but unknown, and a putative phosphorylation site
      (SXE). In addition, the sequences of the 2 enamel-less species display mutations
      revealing that AMTN underwent pseudogenization, which suggests that AMTN is an
      enamel-specific protein.

PMID- 22968159
TI  - Nebulized hypertonic saline containing hyaluronic acid improves tolerability in
      patients with cystic fibrosis and lung disease compared with nebulized hypertonic
      saline alone: a prospective, randomized, double-blind, controlled study.
AB  - BACKGROUND: Hypertonic saline inhalation has been shown to be effective in
      patients with cystic fibrosis and lung disease. However, adverse events including
      marked airway narrowing are reported and a bronchodilator must be given before
      the administration of the product. METHODS: We carried out a prospective,
      randomized, double-blind, parallel-group, controlled study of a hypertonic saline
      solution containing hyaluronic acid (Hyaneb) versus standard hypertonic saline
      therapy to assess whether the presence of hyaluronic acid would improve the
      tolerability of hypertonic saline. RESULTS AND CONCLUSIONS: The results showed
      that nebulized Hyaneb was more effective in reducing the need for beta(2)
      bronchodilators and caused a significant reduction in the incidence of adverse
      effects compared with nebulized hypertonic saline solution alone. Its safety
      profile indicates that Hyaneb can be used for the treatment of lung disease in
      cystic fibrosis.

PMID- 22968161
TI  - The association between severe obesity and characteristics of failed fertilized
      oocytes.
AB  - STUDY QUESTION: Is the cytoskeletal and chromosomal organization of failed
      fertilized oocytes from severely obese patients (BMI >= 35 kg/m2) altered
      compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m2)? SUMMARY
      ANSWER: Compared with normal BMI patients, severe obesity was associated with a
      greater prevalence of spindle anomalies and non-aligned chromosomes in failed
      fertilized oocytes. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Obesity is associated
      with poor reproductive outcomes, but little is known regarding the underlying
      mechanisms. To address potential mechanisms, our study compared the cytoskeletal
      and chromosome organization in failed fertilized oocytes from severely obese and
      normal BMI patients. DESIGN: The study population was drawn from IVF patients
      treated in a hospital-based infertility clinic between February 2010 and July
      2011. The prevalence of meiotic spindle and chromosome alignment anomalies in
      failed fertilized oocytes from patients with severe obesity (i.e. Class II and
      III; BMI 35.0-50.1 kg/m2) was compared with those from patients with normal BMI
      (BMI 18.5-24.9 kg/m2). Oocytes were fixed and then labeled for tubulin, actin and
      chromatin. Spindle number and integrity, as well as chromosome alignment, were
      assessed using immunofluorescence microscopy and, in some cases, confocal
      microscopy. Generalized estimating equations were applied, which account for the
      correlation among oocytes from the same patient to estimate odds ratio (OR), 95%
      confidence intervals (CIs) and two-sided Wald P-values. Models were adjusted for
      continuous age at cycle start, cycle type (IVF or ICSI) and polycystic ovarian
      syndrome (PCOS) a priori. PARTICIPANTS AND SETTING: University-affiliated
      infertility clinic. A total of 276 oocytes that failed to fertilize from 137
      patients were evaluated: 105 oocytes from severely obese women (n = 47) and 171
      oocytes from normal BMI patients (n = 90). MAIN RESULTS AND THE ROLE OF CHANCE:
      (i) Significantly more oocytes from the severely obese group exhibited two
      spindles compared with those from the normal BMI group (58.9 versus 35.1%; OR =
      2.68, CI = 1.39-5.15, P-value = 0.003). (ii) Among oocytes with a single spindle,
      those from severely obese patients showed a significantly higher prevalence of
      disarranged spindles with non-aligned chromosomes compared with those from normal
      BMI patients (28.6 versus 8.6%; OR = 4.58, CI = 1.05-19.86, P-value = 0.04).
      BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Inclusion of only failed
      fertilized oocytes, small sample size, unknown factors such as non-PCOS
      comorbidity. GENERALIZABILITY TO OTHER POPULATIONS: For this study, by design, it
      is unclear whether the findings are generalizable to successfully fertilized
      oocytes, and whether this oocyte-level influence of obesity is generalizable to
      infertile women who do not undergo stimulation or, more broadly, to spontaneous
      conceptions in fertile women. STUDY FUNDING/COMPETING INTEREST(S): none. TRIAL
      REGISTRATION NUMBER: n/a.

PMID- 22968160
TI  - Fluoroquinolones in the treatment of bronchopulmonary disease in cystic fibrosis.
AB  - Fluoroquinolones are commonly used to treat lung infections in patients with
      cystic fibrosis. These patients are susceptible to lung infection with common
      bacteria such as Staphylococcus aureus and Haemophilus influenzae, but are also
      prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa.
      The good oral bioavailability and broad antimicrobial spectrum of activity,
      including antipseudomonal properties, make this class of antimicrobial
      attractive. We review the evidence assessing the use of fluoroquinolones in the
      context of preventing and eradicating early lung infection and in managing
      chronic lung infection and pulmonary exacerbations. The safety of
      fluoroquinolones and the use of newer agents in the class are also discussed.

PMID- 22968163
TI  - Independent determinants of ascending aortic dilatation in hypertensive patients:
      smoking, endothelial dysfunction, and increased epicardial adipose tissue.
AB  - BACKGROUND: Ascending aortic aneurysm is an uncommon condition with lethal
      consequences. Lately, epicardial adipose tissue (EAT) is acknowledged as an organ
      with important effects on the vascular system. In this study, we aimed to
      investigate whether EAT, cardiovascular risk factors, and vascular structure and
      functions are independently related to ascending aortic dilatation. METHODS AND
      RESULTS: Vascular structure and functions were determined by carotid intima-media
      thickness, pulse wave velocity, and brachial artery flow-mediated dilation. Study
      parameters were compared between 46 patients with a dilated ascending aorta
      (diameter >= 37 mm) and 58 individuals with a normal aortic diameter of <37 mm.
      Ascending aortic diameter significantly correlated with age (r=0.420, P<0.001),
      waist circumference (r=0.235, P=0.032), EAT (r=0.507, P<0.001), mean carotid
      intima-media thickness (r=0.354, P<0.001), flow-mediated dilation (r=-0.513,
      P<0.001), and diastolic blood pressure (r=0.365, P<0.001). Although C-reactive
      protein was related to BMI (r=0.485, P<0.001), waist circumference (r=0.368,
      P=0.001), and EAT (r=0.315, P=0.003), it was not correlated with ascending aortic
      diameter (r=0.092, P=0.403). Linear regression analysis revealed EAT thickness
      (beta: 0.483, P<0.001), smoking (beta: 0.366, P=0.002), and flow-mediated
      dilation (beta: -0.332, P=0.007) as the determinants of ascending aortic
      dilatation. CONCLUSION: On the basis of our findings, smoking, endothelial
      dysfunction, and increased EAT may be suggested as risk factors for ascending
      aortic dilation due to local or systemic effects in hypertensive patients.

PMID- 22968164
TI  - Primaquine toxicity forestalls effective therapeutic management of the endemic
      malarias.
AB  - Treatment of acutely ill patients, informed by a diagnosis of the species of
      Plasmodium involved, has long dominated strategic thinking in malaria
      chemotherapeutics. This bias for both acute illness and access to diagnosis
      resulted in therapeutic strategies poorly suited to malaria as it occurs in
      endemic zones. Most of those malarias do not provoke illness and occur beyond
      diagnostic reach for technical or practical reasons. Therapies effective against
      all species and stages would likely prove more practical in endemic zones,
      especially if safely administered without laboratory screening for
      contraindications. The primary impediment to such therapies is the mild to severe
      hemolytic toxicity of primaquine in patients with glucose-6-phosphate
      dehydrogenase deficiency. Primaquine is the only treatment licensed for therapy
      against relapse caused by dormant liver stages occurring in some species, and
      against the sexual blood stages responsible for transmission to mosquitoes in all
      species. Despite being licensed over 50 years ago, no alternative drugs have been
      developed, and safer dosing regimens of primaquine have not been explored. These
      failures forestalled the emergence of therapies practical for use in endemic
      zones, especially in the context of eliminating transmission.

PMID- 22968165
TI  - Wellness coaching and health-related quality of life: a case-control difference
      in-differences analysis.
AB  - OBJECTIVES: Association between wellness coaching and changes in health-related
      quality of life over 1 year and 2 years was assessed. METHODS: Difference-in
      differences analysis of covariance assessed association between coaching and
      change in 8-item short-form health survey (SF-8) summary scores. Ordered logistic
      models assessed coaching and change in SF-8 individual domain scores. This was a
      case-control study. RESULTS: Participants in at least one coaching program were
      more likely to have increases in social functioning after 1 year and less likely
      to have increases in role physical after 2 years. Participants in nutrition
      coaching had more positive change in mental component summary scores after 1
      year. Participants in stress management had more negative change in mental
      component summary scores after 1 year and after 2 years and had more negative
      change in physical component summary scores after 2 years. CONCLUSIONS: Findings
      were mixed regarding association between coaching and change in health-related
      quality of life.

PMID- 22968166
TI  - Unusual structural motif in a zwitterionic Fe(II) complex of a tetradentate
      phosphine.
AB  - The reaction of meso-DPPEPM (DPPEPM = bis(diphenylphosphino
      ethylphenylphosphino)methane) with one equivalent of FeBr(2) in tetrahydrofuran
      generates a zwitterionic compound [FeBr(kappa(2)-DPPEPM)(kappa(3)-DPPEPM
      FeBr(3))] (1). Compound 1 exhibits an unusual bonding arrangement with two meso
      DPPEPM ligands and one bromide coordinated to a single Fe(II) center. One of the
      DPPEPM ligands binds to iron in a kappa(2) mode via two central phosphorus atoms,
      leaving the terminal phosphines dangling. The second DPPEPM binds through three
      phosphines, whereas the fourth one coordinates to the iron center of an external
      FeBr(3)(-) unit. A 1 : 2 reaction of FeBr(2) and meso-DPPEPM in tetrahydrofuran
      generates [FeBr(kappa(2)-DPPEPM)(kappa(3)-DPPEPM)]Br ([2]Br) in which the
      positive charge on the pseudo-octahedral unit is balanced by free Br(-) as
      opposed to the phosphine-bound FeBr(3)(-) in 1. The compound [2]PF(6) was
      obtained from [2]Br and TlPF(6). Solution structures for 1, [2]Br and [2]PF(6)
      were assigned on the basis of (31)P NMR. For all three compounds the data are
      consistent with five phosphorus atoms bound to the metal.

PMID- 22968167
TI  - A hybridized graphene carrier highway for enhanced thermoelectric power
      generation.
AB  - The decoupling and enhancement of both Seebeck coefficient and electrical
      conductivity were achieved by constructing the c-axis preferentially oriented
      nanoscale Sb(2)Te(3) film on monolayer graphene. The external graphene layer
      provided a highway for charge carriers, which were stored in the thicker binary
      telluride film, due to the extremely high mobility.

PMID- 22968169
TI  - Artichoke and Cynar liqueur: two (not quite) entangled proteomes.
AB  - Combinatorial peptide ligand libraries (CPLLs) have been adopted to investigate
      the proteome of artichoke extracts, of a home-made alcoholic infusion and of the
      Italian Cynar liqueur. The aim of study was not only to perform the deepest
      investigation so far of the artichoke proteome but also to assess the genuineness
      of the commercial aperitif via a three-pronged attack. First, different
      extraction techniques have been used for the characterization of the artichoke's
      proteome, secondly a home-made infusion has been analyzed and finally the
      proteome of the commercial drink was checked. The artichoke proteome has been
      evaluated via prior capture with CPLLs at four different pH (2.2, 4.0, 7.2 and
      9.3) values. Via mass spectrometry analysis of the recovered fractions, after
      elution of the captured populations in 4% boiling SDS, we could identify a total
      of 876 unique gene products in the artichoke extracts, 18 in the home-made
      infusion and no proteins at all in the Italian Cynar liqueur, casting severe
      doubts on the procedure stated by the manufacturer (that should be made by an
      infusion of artichoke leaves plus thirteen different herbs). This could be the
      starting point for investigating the genuineness and natural origin of commercial
      drinks in order to protect consumers from adulterated products.

PMID- 22968170
TI  - Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear
      import of FUS.
AB  - Fused in sarcoma (FUS) is a nuclear protein that carries a proline-tyrosine
      nuclear localization signal (PY-NLS) and is imported into the nucleus via
      Transportin (TRN). Defects in nuclear import of FUS have been implicated in
      neurodegeneration, since mutations in the PY-NLS of FUS cause amyotrophic lateral
      sclerosis (ALS). Moreover, FUS is deposited in the cytosol in a subset of
      frontotemporal lobar degeneration (FTLD) patients. Here, we show that arginine
      methylation modulates nuclear import of FUS via a novel TRN-binding epitope.
      Chemical or genetic inhibition of arginine methylation restores TRN-mediated
      nuclear import of ALS-associated FUS mutants. The unmethylated arginine-glycine
      glycine domain preceding the PY-NLS interacts with TRN and arginine methylation
      in this domain reduces TRN binding. Inclusions in ALS-FUS patients contain
      methylated FUS, while inclusions in FTLD-FUS patients are not methylated.
      Together with recent findings that FUS co-aggregates with two related proteins of
      the FET family and TRN in FTLD-FUS but not in ALS-FUS, our study provides
      evidence that these two diseases may be initiated by distinct pathomechanisms and
      implicates alterations in arginine methylation in pathogenesis.

PMID- 22968171
TI  - A complex immunodeficiency is based on U1 snRNP-mediated poly(A) site
      suppression.
AB  - Biallelic mutations in the untranslated regions (UTRs) of mRNAs are rare causes
      for monogenetic diseases whose mechanisms remain poorly understood. We
      investigated a 3'UTR mutation resulting in a complex immunodeficiency syndrome
      caused by decreased mRNA levels of p14/robld3 by a previously unknown mechanism.
      Here, we show that the mutation creates a functional 5' splice site (SS) and that
      its recognition by the spliceosomal component U1 snRNP causes p14 mRNA
      suppression in the absence of splicing. Histone processing signals are able to
      rescue p14 expression. Therefore, the mutation interferes only with canonical
      poly(A)-site 3' end processing. Our data suggest that U1 snRNP inhibits cleavage
      or poly(A) site recognition. This is the first description of a 3'UTR mutation
      that creates a functional 5'SS causative of a monogenetic disease. Moreover, our
      data endorse the recently described role of U1 snRNP in suppression of intronic
      poly(A) sites, which is here deleterious for p14 mRNA biogenesis.

PMID- 22968172
TI  - Determination of optical properties in heterogeneous turbid media using a
      cylindrical diffusing fiber.
AB  - For interstitial photodynamic therapy (PDT), cylindrical diffusing fibers (CDFs)
      are often used to deliver light. This study examines the feasibility and accuracy
      of using CDFs to characterize the absorption (MU(a)) and reduced scattering
      (MU'(s)) coefficients of heterogeneous turbid media. Measurements were performed
      in tissue-simulating phantoms with MU(a) between 0.1 and 1 cm(-1) and MU'(s)
      between 3 and 10 cm(-1) with CDFs 2 to 4 cm in length. Optical properties were
      determined by fitting the measured light fluence rate profiles at a fixed
      distance from the CDF axis using a heterogeneous kernel model in which the
      cylindrical diffusing fiber is treated as a series of point sources. The
      resulting optical properties were compared with independent measurement using a
      point source method. In a homogenous medium, we are able to determine the
      absorption coefficient MU(a) using a value of MU'(s) determined a priori (uniform
      fit) or MU'(s) obtained by fitting (variable fit) with standard (maximum)
      deviations of 6% (18%) and 18% (44%), respectively. However, the CDF method is
      found to be insensitive to variations in MU'(s), thus requiring a complementary
      method such as using a point source for determination of MU'(s). The error for
      determining MU(a) decreases in very heterogeneous turbid media because of the
      local absorption extremes. The data acquisition time for obtaining the one
      dimensional optical properties distribution is less than 8 s. This method can
      result in dramatically improved accuracy of light fluence rate calculation for
      CDFs for prostate PDT in vivo when the same model and geometry is used for
      forward calculations using the extrapolated tissue optical properties.

PMID- 22968173
TI  - Inhibitory effect of the recombinant Phoneutria nigriventer Tx1 toxin on voltage
      gated sodium channels.
AB  - Phoneutria nigriventer toxin Tx1 (PnTx1, also referred to in the literature as
      Tx1) exerts inhibitory effect on neuronal (Na(V)1.2) sodium channels in a way
      dependent on the holding potential, and competes with MU-conotoxins but not with
      tetrodotoxin for their binding sites. In the present study we investigated the
      electrophysiological properties of the recombinant toxin (rPnTx1), which has the
      complete amino acid sequence of the natural toxin with 3 additional residues: AM
      on the N-terminal and G on the C-terminal. At the concentration of 1.5 MUM, the
      recombinant toxin inhibits Na(+) currents of dorsal root ganglia neurons (38.4 +/
      6.1% inhibition at -80 mV holding potential) and tetrodotoxin-resistant Na(+)
      currents (26.2 +/- 4.9% at the same holding potential). At -50 mV holding
      potential the inhibition of the total current reached 71.3 +/- 2.3% with 1.5 MUM
      rPnTx1. The selectivity of rPnTx1 was investigated on ten different isoforms of
      voltage-gated sodium channels expressed in Xenopus oocytes. The order of potency
      for rPnTx1 was: rNa(V)1.2 > rNa(V)1.7 ~ rNa(V)1.4 >= rNa(V)1.3 > mNa(V)1.6 >=
      hNa(V)1.8. No effect was seen on hNa(V)1.5 and on the arthropods isoforms
      (DmNa(V)1, BGNa(V)1.1a and VdNa(V)1). The IC(50) for Na(V)1.2 was 33.7 +/- 2.9 nM
      with a maximum inhibition of 83.3 +/- 1.9%. The toxin did not alter the voltage
      dependence of channel gating and was effective on Na(V)1.2 channels devoid of
      inactivation. It was ineffective on neuronal calcium channels. We conclude that
      rPnTx1 has a promising selectivity, and that it may be a valuable model to
      achieve pharmacological activities of interest for the treatment of
      channelopathies and neuropathic pain.

PMID- 22968174
TI  - A novel pro-apoptotic effector lactaptin inhibits tumor growth in mice models.
AB  - Lactaptin, a human milk-derived protein, induces apoptosis in cultured tumor
      cells. We designed a recombinant analog of lactaptin (RL2) and tested its
      antitumor activity. The sensitivity of hepatocarcinoma A-1 (HA-1), Lewis lung
      carcinoma, and Ehrlich carcinoma to RL2 were tested to determine the most
      reliable in vitro animal model. HA-1 cells, which had the highest sensitivity to
      RL2, were transplanted into A/Sn mice to investigate RL2 antitumor activity in
      vivo. Investigation of the molecular effects of RL2 shows that RL2 induces
      apoptotic transformation of HA-1 cells in vitro: phosphatidylserine translocation
      from inner side of the lipid bilayer to the outer one and dissipation of the
      mitochondrial membrane potential. Repetitive injections of RL2 (5-50 mg/kg) for 3
      5 days effectively inhibited ascites and solid tumor transplant growth when
      administered intravenously or intraperitoneally, without obvious side effects.
      The solid tumor inhibitory effect of RL2 (5 i.v. injections, cumulative dose 125
      mg/kg) was comparable with that of cyclophosphamide at a therapeutic dose (5 i.v.
      injections, cumulative dose 150 mg/kg). In combination therapy with
      cyclophosphamide, RL2 had an additive antitumor effect for ascites-producing
      tumors. Histomorphometric analysis indicated a three-fold reduction of
      spontaneous metastases in the liver of RL2-treated mice with solid tumor
      transplants in comparison with control animals. Repeated RL2 treatment
      substantially prolonged the lifespan of mice with intravenously injected tumor
      cells. Recombinant analog of lactaptin effectively induced apoptosis of tumor
      cells in vitro and suppressed the growth of sensitive tumors and metastases in
      vivo.

PMID- 22968176
TI  - Large-scale synthesis of Cu2SnS3 and Cu(1.8)S hierarchical microspheres as
      efficient counter electrode materials for quantum dot sensitized solar cells.
AB  - Exploration of new catalytic semiconductors with novel structures as counter
      electrode materials is a promising approach to improve performances of quantum
      dot sensitized solar cells (QDSSCs). In this work, nearly mono-disperse
      tetragonal Cu(2)SnS(3) (CTS) and rhombohedral Cu(1.8)S hierarchical microspheres
      with nanometer-to-micrometer dimensions have been synthesized respectively via a
      simple solvothermal approach. These microspheres are also demonstrated as
      efficient counter electrode materials in solar cells using ZnO/ZnSe/CdSe
      nanocables as photoanode and polysulfide (S(n)(2-)/S(2-)) solution as
      electrolyte. While copper sulfide is regarded as one of the most effective
      counter electrode materials in QDSSCs, we demonstrate the CTS microspheres to
      show higher electrocatalytic activity for the reduction of polysulfide
      electrolyte than the Cu(1.8)S microspheres. This contributes to obvious
      enhancement of photocurrent density (J(SC)) and fill factor (FF). Power
      conversion efficiency (PCE) is significantly enhanced from 0.25% for the cell
      using a pure FTO (SnO(2):F) glass as counter electrode, to 3.65 and 4.06% for the
      cells using counter electrodes of FTO glasses coated respectively with Cu(1.8)S
      and CTS microspheres.

PMID- 22968175
TI  - Frequency distribution analysis of activation times and regional fibrosis in
      murine Scn5a+/- hearts: the effects of ageing and sex.
AB  - Both Brugada Syndrome (BrS) and progressive cardiac conduction defect (PCCD) are
      associated respectively with diffuse and discrete alterations in conduction
      pathways affected by ageing and sex. This study assessed for contributions of
      such processes to the mechanism of conduction changes in Scn5a(+/-) and WT hearts
      stratified by age (3 and 12 months) and sex. In vivo electrocardiographic chest
      lead assessment demonstrated greater incidences of bundle branch block in all
      Scn5a(+/-) mice compared to WT. Frequency analysis of right ventricular (RV)
      epicardial activation obtained from a 64-channel multi-electrode array
      demonstrated greater prominence of late conducting components in Scn5a(+/-)
      compared to WT male, and in male compared to female Scn5a(+/-) following
      stratification by genotype and sex. Similar differences were observed between old
      male Scn5a(+/-) and young male Scn5a(+/-), old female Scn5a(+/-), and old male
      WT, following stratification by genotype, age and sex. These findings directly
      correlated with histomorphometric assessment of regional fibrosis in both septa
      and free walls preferentially involving the RV. We demonstrate complex
      alterations in conduction distributions suggesting a conversion of normal to slow
      conducting tissue, modulated by ageing and sex, coupled with fibrosis in Scn5a(+/
      ) hearts. These features suggest an overlap between pathophysiological processes
      related to BrS and PCCD in Scn5a(+/-) hearts.

PMID- 22968177
TI  - GRADE guidelines-an introduction to the 10th-13th articles in the series.

PMID- 22968178
TI  - There are some circumstances where the stepped-wedge cluster randomized trial is
      preferable to the alternative: no randomized trial at all. Response to the
      commentary by Kotz and colleagues.

PMID- 22968179
TI  - Vascular and heart diseases in the incumbent presidents and vice presidents of
      the United States of america: a medical-historical perspective.
AB  - Vascular diseases have been the major cause of death and disability in presidents
      and vice presidents of the United States. Untreated hypertension and cigarette
      smoking have contributed greatly to this increased morbidity and mortality risk,
      which has impacted on historical events, especially in the 20th century. In this
      article, the medical histories of those incumbent Presidents and Vice Presidents
      who suffered from coronary artery and cerebrovascular diseases will be reviewed.
      A discussion of how atrial fibrillation has affected the Presidents is also
      included.

PMID- 22968180
TI  - Saphenous vein graft disease:  review of pathophysiology, prevention, and
      treatment.
AB  - Saphenous vein graft (SVG) disease after coronary artery bypass grafting (CABG)
      occurs in three phases: thrombosis, intimal hyperplasia, and atherosclerosis.
      Within the first month, thrombosis plays a major role. From month 1 to month 12,
      intimal hyperplasia occurs. Beyond 12 months, atherosclerosis becomes the primary
      cause for late graft failure. Endothelial damage has been shown to be the major
      underlying pathophysiology of SVG disease. Many factors contribute to endothelial
      damage from the moment the vein is harvested to when the vein is grafted into an
      arterial environment. To address this disease process, various therapeutic
      modalities, from surgical methods to medical treatment, have been evaluated.
      Surgically, the technical method of harvesting the vein has been shown to affect
      SVG patency. From a pharmacologic perspective, only two guideline class I
      recommended medications, aspirin and statins, have been shown to improve short-
      and long-term SVG patency after CABG. Despite these surgical and medical
      advances, SVG disease remains a significant problem with 1-year patency rates of
      89% dropping to 61% after 10 years. This review discusses the pathogenesis of SVG
      disease, predictors of SVG failure, and current surgical and pharmacologic
      therapies to address SVG disease, including possible future treatment.

PMID- 22968181
TI  - Second-hand tobacco smoke and cardiovascular disease risk: an epidemiological
      review.
AB  - In this review, we have sought to examine the epidemiological, basic science, and
      public health data regarding the association between second-hand smoke (SHS)
      exposure and the development of coronary heart disease (CHD). SHS increases the
      risk of CHD by 25-30% according to multiple cohort, case-control, and meta
      analytical studies. Physiologic and basic science research suggest that the
      mechanisms by which SHS affects the cardiovascular system are multiple and
      include increased thrombogenesis and low-density lipoprotein oxidation, decreased
      exercise tolerance, dysfunctional flow-mediated vasodilatation, and activation of
      inflammatory pathways with concomitant oxidative damage and impaired vascular
      repair. As a result, chronic exposure promotes atherogenesis and the development
      of cardiovascular disease, increasing the risk of having an acute coronary
      syndrome (ACS). With the implementation of statewide and nationwide public smoke
      free legislation across the United States and Europe, respectively, over the last
      10-15 years, there has been a significant and reciprocal decline in the incidence
      of emergency admissions for ACS by an average 17% despite persistent attempts on
      the part of the tobacco industry to diminish the correlation between SHS exposure
      and CHD. These findings underscore the importance of the effects of smoking
      legislation on community health.

PMID- 22968182
TI  - Bu4NI-catalyzed benzylic acyloxylation of alkylarenes with aromatic aldehydes.
AB  - An nBu(4)NI-catalyzed benzylic C-H acyloxylation of alkylarenes with readily
      available aromatic aldehydes has been developed. These reactions occur under mild
      and clean reaction conditions using tert-butyl hydroperoxide as the green
      terminal oxidant.

PMID- 22968184
TI  - Everolimus and erlotinib as second- or third-line therapy in patients with
      advanced non-small-cell lung cancer.
AB  - INTRODUCTION: The epidermal growth factor receptor inhibitor erlotinib is an
      approved treatment for chemotherapy-refractory advanced non-small-cell lung
      cancer (NSCLC). Because activated epidermal growth factor receptor signals
      through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin
      (mTOR) pathway, adding the oral mTOR inhibitor everolimus to erlotinib may
      improve efficacy by blocking multiple components of the same pathway. We
      conducted a phase I study to determine feasible dosages of combination therapy
      with erlotinib and everolimus for previously treated metastatic or unresectable
      NSCLC. METHODS: Participants had advanced NSCLC progressing after two or less
      previous chemotherapy regimens. Feasibility of daily/weekly everolimus plus daily
      erlotinib was determined using a 6 + 6 dose-escalation design based on the rate
      of dose-limiting toxicities. Antitumor activity was assessed by the Response
      Evaluation Criteria In Solid Tumors study. RESULTS: Of the 94 patients enrolled,
      90% had stage IV NSCLC, 19% never smoked, and 15% were current smokers. Eighty
      nine patients experienced one or more adverse events possibly related to any
      study medication. The most common dose-limiting toxicities were stomatitis (n =
      5), rash (n = 4), and diarrhea (n = 3). Maximum tolerated doses were everolimus 5
      mg per day or 50 mg per week plus erlotinib 150 mg per day. In daily everolimus
      cohorts (n = 74), nine patients achieved a complete/partial response and 28 had
      stable disease (median duration disease control, 9.3 months). In weekly
      everolimus cohorts (n = 20), no tumor response was observed; seven patients had
      stable disease (median duration, 9.6 months). CONCLUSIONS: Combination therapy
      with everolimus 5 mg per day or 50 mg per week and erlotinib 150 mg per day
      provided acceptable tolerability and disease control. A randomized phase II study
      evaluating this combination in comparison with erlotinib alone is complete and is
      being analyzed.

PMID- 22968185
TI  - Long-term surveillance of ground-glass nodules: evidence from the MILD trial.
AB  - INTRODUCTION: The purpose of this study was to evaluate the natural evolution of
      ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD)
      trial, which adopted a nonsurgical approach to this subset of lesions. METHODS:
      From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs
      were identified from 1866 individuals who underwent baseline low-dose computed
      tomography. The features of GGNs were assessed and compared with the
      corresponding repeat low-dose computed tomographies after a mean time of 50.26 +/
      7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs.
      The average of the maximum and the minimum diameters for both pGGNs and psGGNs
      and the maximum diameter of the solid portion of psGGNs were manually measured.
      At follow-up, GGNs were classified as follows: resolved, decreased, stable, or
      progressed (according to three defined growth patterns). RESULTS: A total of 15
      of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%)
      remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid
      component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained
      stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid
      component larger than 5 mm remained stable, and the other decreased in size. Four
      lung cancers were detected among the GGN subjects, but only one arose from a
      psGGN, and was resected in stage Ia. CONCLUSIONS: The progression rate of the
      GGNs toward clinically relevant disease was extremely low in the MILD trial and
      supports an active surveillance attitude.

PMID- 22968187
TI  - Pancreatic steatosis and its relationship to beta-cell dysfunction in humans:
      racial and ethnic variations.
AB  - OBJECTIVE: To evaluate racial/ethnic differences in pancreatic triglyceride (TG)
      levels and their relationship to beta-cell dysfunction in humans. RESEARCH DESIGN
      AND METHODS: We studied black, Hispanic, and white adults who completed three
      research visits: screening and an oral glucose tolerance test; frequently sampled
      intravenous glucose tolerance tests for evaluation of beta-cell function and
      insulin resistance; and proton magnetic resonance spectroscopy for evaluation of
      pancreatic and hepatic TG levels. RESULTS: Pancreatic TG levels were higher in
      Hispanics and whites than in blacks (P = 0.006). Hepatic TG levels were highest
      in Hispanics (P = 0.004). Compensatory insulin secretion and disposition index
      were higher in blacks (P = 0.003 and P = 0.024, respectively). Insulin
      sensitivity was comparable between Hispanics and blacks and was lower than in
      whites (P = 0.005). In blacks, compensatory insulin secretion increased steeply
      with small increments in pancreatic TG levels (R(2) = 0.45, slope = 247). In
      whites, the range of pancreatic TG levels was higher, and the slope was less
      steep than in blacks (R(2) = 0.27, slope = 27). In Hispanics, pancreatic TG
      levels were similar to those of whites, but compensatory insulin secretion was
      described by a combination of pancreatic and hepatic TG levels and visceral fat
      mass ( R(2) = 0.32). CONCLUSIONS: In a multiethnic sample of adults with mild
      obesity and without diabetes, we found striking ethnic differences in the levels
      of pancreatic TGs and in the relationship between pancreatic TGs and beta-cell
      dysfunction. Our data implicate pancreatic TG content measured by proton magnetic
      resonance spectroscopy as a noninvasive novel biomarker for pancreatic beta-cell
      dysfunction, especially in the Hispanic population.

PMID- 22968189
TI  - Pre-clinical studies of toxin-specific nanobodies: evidence of in vivo efficacy
      to prevent fatal disturbances provoked by scorpion envenoming.
AB  - Scorpions represent a significant threat to humans and animals in various
      countries throughout the world. Recently, we introduced Nanobodies (Nbs) to
      combat more efficiently scorpion envenoming and demonstrated the performance of
      NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis
      hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is
      far more protective than the classic Fab'(2) based therapy and is the most
      efficient antivenom therapy against scorpion sting in preclinical studies. Now we
      investigate the biodistribution and pharmacokinetics of (99m)Tc labeled Nbs by in
      vivo imaging in rodents and compared these data with those of the Fab'(2) product
      (PAS). The pharmacodynamics of the Nbs was investigated in rats by in vivo
      echocardiography and it is shown that NbF12-10 prevents effectively the
      hemodynamic disturbances induced by a lethal dose of venom. Moreover, even a late
      injection of NbF12-10 restores the heart rate and brings the blood pressure to
      baseline values. Histology confirms that NbF12-10 prevents lung and heart lesions
      of treated mice after envenoming. In conjunction, in this preclinical study, we
      provide proof of concept that NbF12-10 prevents effectively the fatal
      disturbances induced by Androctonus venom, and that the Nanobody based
      therapeutic has a potential to substitute the classic Fab'(2) based product as
      immunotherapeutic in scorpion envenoming. Further clinical study using larger
      cohorts of animals should be considered to confirm the full protecting potential
      of our NbF12-10.

PMID- 22968190
TI  - Melanin, a promising radioprotector: mechanisms of actions in a mice model.
AB  - The radioprotective effect of extracellular melanin, a naturally occurring
      pigment, isolated from the fungus Gliocephalotrichum simplex was examined in
      BALB/C mice, and the probable mechanism of action was established. At an
      effective dose of 50mg/kg body weight, melanin exhibited both prophylactic and
      mitigative activities, increasing the 30-day survival of mice by 100% and 60%,
      respectively, after exposure to radiation (7Gy, whole body irradiation (WBI)).
      The protective activity of melanin was primarily due to inhibition of radiation
      induced hematopoietic damages as evidenced by improvement in spleen parameters
      such as index, total cellularity, endogenous colony forming units, and
      maintenance of circulatory white blood cells and platelet counts. Melanin also
      reversed the radiation-induced decrease in ERK phosphorylation in splenic tissue,
      which may be the key feature in its radioprotective action. Additionally, our
      results indicated that the sustained activation of AKT, JNK and P38 proteins in
      splenic tissue of melanin pre-treated group may also play a secondary role. This
      was also supported by the fact that melanin could prevent apoptosis in splenic
      tissue by decreasing BAX/Bcl-XL ratio, and increasing the expressions of the
      proliferation markers (PCNA and Cyclin D1), compared to the radiation control
      group. Melanin also reduced the oxidative stress in hepatic tissue and abrogated
      immune imbalance by reducing the production of pro-inflammatory cytokines (IL6
      and TNFalpha). In conclusion, our results confirmed that fungal melanin is a very
      effective radioprotector against WBI and the probable mechanisms of
      radioprotection are due to modulation in pro-survival (ERK) signaling, prevention
      of oxidative stress and immunomodulation.

PMID- 22968191
TI  - Assessment of radiation-induced second cancer risks in proton therapy and IMRT
      for organs inside the primary radiation field.
AB  - There is clinical evidence that second malignancies in radiation therapy occur
      mainly within the beam path, i.e. in the medium or high-dose region. The purpose
      of this study was to assess the risk for developing a radiation-induced tumor
      within the treated volume and to compare this risk for proton therapy and
      intensity-modulated photon therapy (IMRT). Instead of using data for specific
      patients we have created a representative scenario. Fully contoured age- and
      gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a
      treatment planning system and tumor volumes were contoured based on patients
      treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for
      IMRT and proton therapy treatments were generated. Lifetime attributable risks
      (LARs) for developing a second malignancy were calculated using a risk model
      considering cell kill, mutation, repopulation, as well as inhomogeneous organ
      doses. For standard fractionation schemes, the LAR for developing a second
      malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year
      old optic glioma patient treated with IMRT considering a soft-tissue carcinoma
      risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14
      year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma
      cases the risks based on a sarcoma model were typically higher than the carcinoma
      risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from
      proton therapy turned out to be lower by at least a factor of 2 and up to a
      factor of 10. This is mainly due to lower total energy deposited in the patient
      when using proton beams. However, the comparison of a three-field and four-field
      proton plan also shows that the distribution of the dose, i.e. the particular
      treatment plan, plays a role. When using different fractionation schemes, the
      estimated risks roughly scale with the total dose difference in%. In conclusion,
      proton therapy can significantly reduce the risk for developing an in-field
      second malignancy. The risk depends on treatment planning parameters, i.e. an
      analysis based on our formalism could be applied within treatment planning
      programs to guide treatment plans for pediatric patients.

PMID- 22968192
TI  - The role of pitch and temporal diversity in the perception and production of
      musical sequences.
AB  - In two experiments we explored how the dimensions of pitch and time contribute to
      the perception and production of musical sequences. We tested how dimensional
      diversity (the number of unique categories in each dimension) affects how pitch
      and time combine. In Experiment 1, 18 musically trained participants rated the
      complexity of sequences varying only in their diversity in pitch or time; a
      separate group of 18 pianists reproduced these sequences after listening to them
      without practice. Overall, sequences with more diversity were perceived as more
      complex, but pitch diversity influenced ratings more strongly than temporal
      diversity. Further, although participants perceived sequences with high levels of
      pitch diversity as more complex, errors were more common in the sequences with
      higher diversity in time. Sequences in Experiment 2 exhibited diversity in both
      pitch and time; diversity levels were a subset of those tested in Experiment 1.
      Again diversity affected complexity ratings and errors, but there were no
      statistical interactions between dimensions. Nonetheless, pitch diversity was the
      primary factor in determining perceived complexity, and again temporal errors
      occurred more often than pitch errors. Additionally, diversity in one dimension
      influenced error rates in the other dimension in that both error types were more
      frequent relative to Experiment 1. These results suggest that although pitch and
      time do not interact directly, they are nevertheless not processed in an
      informationally encapsulated manner. The findings also align with a dimensional
      salience hypothesis, in which pitch is prioritised in the processing of typical
      Western musical sequences.

PMID- 22968193
TI  - Does how I look at what you're doing depend on what I'm doing?
AB  - Previous studies showed that people proactively gaze at the target of another's
      action by taking advantage of their own motor representation of that action. But
      just how selectively is one's own motor representation implicated in another's
      action processing? If people observe another's action while performing a
      compatible or an incompatible action themselves, will this impact on their gaze
      behaviour? We recorded proactive eye movements while participants observed an
      actor grasping small or large objects. The participants' right hand either freely
      rested on the table or held with a suitable grip a large or a small object,
      respectively. Proactivity of gaze behaviour significantly decreased when
      participants observed the actor reaching her target with a grip that was
      incompatible with respect to that used by them to hold the object in their own
      hand. This indicates that effective observation of action may depend on what one
      is actually doing, being actions observed best when the suitable motor
      representations may be readily recruited.

PMID- 22968194
TI  - Sensory-based mechanism for delayed motor intention.
AB  - Prospective motor learning (PML) can be defined as learning an action to be
      performed in the future. The privileged retrieval mechanism behind this delayed
      motor performance remains unknown. From a motor control and learning perspective,
      we may conceive of two forms of retrieval: a stimulus- and an intention-based
      control. Retrieval from intention-based control is based on the anticipation of
      intended sensory effects related to an action in order to select and control the
      appropriate motor procedure (i.e., the ideomotor mechanism). In contrast, in a
      stimulus-based control a connection between stimuli-features and their related
      action-features is stored in the memory and serves as the retrieval mechanism. In
      this view, action retrieval from external stimuli is based on the detection of
      events in the environment to perform the intended behaviour (i.e., the
      sensorimotor mechanism). In this study, we report an advantage in the action
      retrieval for participants who use an intention-based mode of control in
      comparison to a stimulus-based control. Furthermore, a control task reveals that
      the intention-based advantage is specific to PML. Our findings show that PML is
      benefited by mental anticipation of a sensory effect that is efficiently
      processed through an ideomotor mechanism to fulfil delayed motor intentions.

PMID- 22968195
TI  - Effects of deviant trials on precue-based versus memory-based switching among two
      or four tasks.
AB  - In two experiments, the effects of an introduction of deviant trials on precue
      based and memory-based task switching were investigated. Deviant trials were
      trials that deviated from task foreknowledge as induced either by precues or
      memory of the task sequence. The experiments differed with respect to the number
      of tasks to be switched among (two in Experiment 1, four in Experiment 2). In
      Experiment 1, the introduction of deviant trials had a detrimental effect on
      precue-based task preparation, but had little impact on memory-based preparation.
      The latter observation was due to the fact that there was little evidence for
      memory-based preparation at the outset. In Experiment 2, introducing deviant
      trials had little effect on either precue-based or memory-based preparation. In
      contrast to Experiment 1, in Experiment 2 memory-based preparation was as
      effective as precue-based preparation.

PMID- 22968196
TI  - Enhanced Li+ ion transport in LiNi0.5Mn1.5O4 through control of site disorder.
AB  - High voltage spinel LiNi(0.5)Mn(1.5)O(4) is a very promising cathode material for
      lithium ion batteries that can be used to power hybrid electrical vehicles
      (HEVs). Through careful control of the cooling rate after high temperature
      calcination, LiNi(0.5)Mn(1.5)O(4) spinels with different disordered phase and/or
      Mn(3+) contents have been synthesized. It is revealed that during the slow
      cooling process (<3  degrees C min(-1)), oxygen deficiency is reduced by the
      oxygen intake, thus the residual Mn(3+) amount is also decreased in the spinel
      due to charge neutrality. In situ X-ray diffraction (XRD) demonstrates that the
      existence of a disordered phase fundamentally changes the spinel phase transition
      pathways during the electrochemical charge-discharge process. The presence of an
      appropriate amount of oxygen deficiency and/or Mn(3+) is critical to accelerate
      the Li(+) ion transport within the crystalline structure, which is beneficial to
      enhance the electrochemical performance of LiNi(0.5)Mn(1.5)O(4).
      LiNi(0.5)Mn(1.5)O(4) with an appropriate amount of disordered phase offers high
      rate capability (96 mAh g(-1) at 10  degrees C) and excellent cycling performance
      with 94.8% capacity retention after 300 cycles. The fundamental findings in this
      work can be widely applied to guide the synthesis of other mixed oxides or
      spinels as high performance electrode materials for lithium ion batteries.

PMID- 22968197
TI  - A bioresponsive controlled-release biosensor using Au nanocages capped with an
      aptamer-based molecular gate and its application in living cells.
AB  - A novel bioresponsive controlled-release biosensor using Au nanocages capped with
      an aptamer-based molecular gate was reported for the first time. The use of
      aptamers as caps has proven to be a suitable method for the preparation of "bio
      gated" delivery systems that can be selectively opened in the presence of target
      biomolecules.

PMID- 22968198
TI  - Emerging photoluminescence in azo-pyridine intercalated graphene oxide layers.
AB  - Inspite of being a potential material for electronic applications graphene
      possesses very poor optical properties, which need to be modified to make it
      suitable for optoelectronic devices. To achieve superior optical properties,
      graphene oxide (GO) sheets are functionalized with azo-pyridine to form a new
      intercalated structure with an interlayer separation of 0.9 nm. These azo
      pyridine intercalated GO sheets show superior optical properties with bright blue
      emission via excited state intra-molecular proton transfer (ESIPT) which have
      potential applications in graphene based optoelectronic devices.

PMID- 22968199
TI  - Ocular thelaziosis due to Thelazia callipaeda in a cat from northeastern
      Portugal.
AB  - Cases of feline thelaziosis have seldom been published in the scientific
      literature. We report the first autochthonous case of feline ocular thelaziosis
      in Portugal caused by Thelazia callipaeda and suggest that this infestation
      should be included among differential diagnoses of ocular diseases in cats from
      this country.

PMID- 22968200
TI  - A case of scapular avulsion with concomitant scapular fracture in a cat.
AB  - An 11-year-old cat was referred following vehicular trauma for evaluation and
      treatment of right thoracic limb lameness which was non-responsive to
      conservative management. Gait assessment revealed a severe weight-bearing right
      thoracic limb lameness, soft tissue swelling over the dorsal border of the
      scapula, crepitus upon direct palpation over the scapula and lateralisation of
      the scapula upon adduction of the distal limb allowing a diagnosis of scapular
      avulsion to be made. Computed tomography (CT) demonstrated a comminuted fracture
      of the right scapula and a tear of the serratus ventralis muscle. The scapular
      fractures involved the caudal scapular angle and therefore a circumcostal suture
      was not placed. Stabilisation was achieved through reattachment of the scapula to
      the serratus ventralis muscle with sutures placed through small holes in the
      dorsal and cranial borders of the scapula. Follow-up revealed resolution of
      lameness at 14 weeks postoperatively but non-union of the scapular fractures as
      evidenced by repeat CT. This case report details the medium-term outcome
      following this very unusual injury and contributes to the sparse literature
      regarding the progression of conservatively managed scapular fractures. It
      demonstrates that full return to function can occur following this injury even
      when radiographic union of the fracture is not achieved. To our knowledge this is
      the first report of this specific combination of injuries detailed with medium
      term and advanced imaging follow-up.

PMID- 22968201
TI  - An integrated MULED optrode for optogenetic stimulation and electrical recording.
AB  - In this letter, we developed an integrated neural probe prototype for optogenetic
      stimulation by microscale light-emitting diode (MULED) and simultaneous recording
      of neural activities with microelectrodes on a single-polyimide platform.
      Optogenetics stimulates in vivo neural circuits with high-cellular specificity
      achieved by genetic targeting and precise temporal resolution by interaction of
      light-gated ion channels with optical beam. In our newly developed optrode probe,
      during optogenetic stimulation of neurons, continuous sensing of neuronal
      activities in vicinity of the activation site can provide feedback to stimulation
      or examine local responses in signal pathways. In the device, focusing the light
      from the MULED was achieved with an integrated photo-polymerized lens. The
      efficacy of the optrode for cortical stimulation and recording was tested on mice
      visual cortex neurons expressing channelrhodopsin-2. Stimulation intensity and
      frequency-dependent spiking activities of visual cortex were recorded. Our device
      has shown advantages over fiber-coupled laser-based optrode in terms of closed
      loop integration, single-implant compactness and lower electrical power
      requirements, which would be clinically applicable for future prosthetic
      applications in personalized medicine.

PMID- 22968202
TI  - Group-sparse representation with dictionary learning for medical image denoising
      and fusion.
AB  - Recently, sparse representation has attracted a lot of interest in various areas.
      However, the standard sparse representation does not consider the intrinsic
      structure, i.e., the nonzero elements occur in clusters, called group sparsity.
      Furthermore, there is no dictionary learning method for group sparse
      representation considering the geometrical structure of space spanned by atoms.
      In this paper, we propose a novel dictionary learning method, called Dictionary
      Learning with Group Sparsity and Graph Regularization (DL-GSGR). First, the
      geometrical structure of atoms is modeled as the graph regularization. Then,
      combining group sparsity and graph regularization, the DL-GSGR is presented,
      which is solved by alternating the group sparse coding and dictionary updating.
      In this way, the group coherence of learned dictionary can be enforced small
      enough such that any signal can be group sparse coded effectively. Finally, group
      sparse representation with DL-GSGR is applied to 3-D medical image denoising and
      image fusion. Specifically, in 3-D medical image denoising, a 3-D processing
      mechanism (using the similarity among nearby slices) and temporal regularization
      (to perverse the correlations across nearby slices) are exploited. The
      experimental results on 3-D image denoising and image fusion demonstrate the
      superiority of our proposed denoising and fusion approaches.

PMID- 22968203
TI  - A novel algorithm for Bluetooth ECG.
AB  - In wireless transmission of ECG, data latency will be significant when battery
      power level and data transmission distance are not maintained. In applications
      like home monitoring or personalized care, to overcome the joint effect of
      previous issues of wireless transmission and other ECG measurement noises, a
      novel filtering strategy is required. Here, a novel algorithm, identified as peak
      rejection adaptive sampling modified moving average (PRASMMA) algorithm for
      wireless ECG is introduced. This algorithm first removes error in bit pattern of
      received data if occurred in wireless transmission and then removes baseline
      drift. Afterward, a modified moving average is implemented except in the region
      of each QRS complexes. The algorithm also sets its filtering parameters according
      to different sampling rate selected for acquisition of signals. To demonstrate
      the work, a prototyped Bluetooth-based ECG module is used to capture ECG with
      different sampling rate and in different position of patient. This module
      transmits ECG wirelessly to Bluetooth-enabled devices where the PRASMMA algorithm
      is applied on captured ECG. The performance of PRASMMA algorithm is compared with
      moving average and S-Golay algorithms visually as well as numerically. The
      results show that the PRASMMA algorithm can significantly improve the ECG
      reconstruction by efficiently removing the noise and its use can be extended to
      any parameters where peaks are importance for diagnostic purpose.

PMID- 22968204
TI  - A new 3-D tool for planning plastic surgery.
AB  - Face plastic surgery (PS) plays a major role in today medicine. Both for
      reconstructive and cosmetic surgery, achieving harmony of facial features is an
      important, if not the major goal. Several systems have been proposed for
      presenting to patient and surgeon possible outcomes of the surgical procedure. In
      this paper, we present a new 3-D system able to automatically suggest, for
      selected facial features as nose, chin, etc., shapes that aesthetically match the
      patient's face. The basic idea is suggesting shape changes aimed to approach
      similar but more harmonious faces. To this goal, our system compares the 3-D scan
      of the patient with a database of scans of harmonious faces, excluding the
      feature to be corrected. Then, the corresponding features of the  k most similar
      harmonious faces, as well as their average, are suitably pasted onto the
      patient's face, producing k+1 aesthetically effective surgery simulations. The
      system has been fully implemented and tested. To demonstrate the system, a 3-D
      database of harmonious faces has been collected and a number of PS treatments
      have been simulated. The ratings of the outcomes of the simulations, provided by
      panels of human judges, show that the system and the underlying idea are
      effective.

PMID- 22968205
TI  - A wearable cardiac monitor for long-term data acquisition and analysis.
AB  - A low-power wearable ECG monitoring system has been developed entirely from
      discrete electronic components and a custom PCB. This device removes all loose
      wires from the system and minimizes the footprint on the user. The monitor
      consists of five electrodes, which allow a cardiologist to choose from a variety
      of possible projections. Clinical tests to compare our wearable monitor with a
      commercial clinical ECG recorder are conducted on ten healthy adults under
      different ambulatory conditions, with nine of the datasets used for analysis.
      Data from both monitors were synchronized and annotated with PhysioNet's waveform
      viewer WAVE (physionet.org) [1]. All gold standard annotations are compared to
      the results of the WQRS detection algorithm [2] provided by PhysioNet. QRS
      sensitivity and QRS positive predictability are extracted from both monitors to
      validate the wearable monitor.

PMID- 22968206
TI  - Compressed sensing of EEG for wireless telemonitoring with low energy consumption
      and inexpensive hardware.
AB  - Telemonitoring of electroencephalogram (EEG) through wireless body-area networks
      is an evolving direction in personalized medicine. Among various constraints in
      designing such a system, three important constraints are energy consumption, data
      compression, and device cost. Conventional data compression methodologies,
      although effective in data compression, consumes significant energy and cannot
      reduce device cost. Compressed sensing (CS), as an emerging data compression
      methodology, is promising in catering to these constraints. However, EEG is
      nonsparse in the time domain and also nonsparse in transformed domains (such as
      the wavelet domain). Therefore, it is extremely difficult for current CS
      algorithms to recover EEG with the quality that satisfies the requirements of
      clinical diagnosis and engineering applications. Recently, block sparse Bayesian
      learning (BSBL) was proposed as a new method to the CS problem. This study
      introduces the technique to the telemonitoring of EEG. Experimental results show
      that its recovery quality is better than state-of-the-art CS algorithms, and
      sufficient for practical use. These results suggest that BSBL is very promising
      for telemonitoring of EEG and other nonsparse physiological signals.

PMID- 22968207
TI  - Cognition-emotion interactions are modulated by working memory capacity in
      individuals with schizophrenia.
AB  - Prior research provides evidence for aberrant cognition-emotion interactions in
      schizophrenia. In the current study, we aimed to extend these findings by
      administering the "distractor devaluation" task to 40 individuals with
      schizophrenia and 32 demographically matched healthy controls. The task consisted
      of a simple visual search task for neutral faces, followed by an evaluative
      response made for one of the search items (or a novel item) to determine whether
      prior attentional selection results in a devaluation of a previously unattended
      stimulus. We also manipulated working memory demands by preceding the search
      array with a memory array that required subjects to hold 0, 1, or 2 items in
      working memory while performing the search array and devaluation task, to
      determine whether the normative process by which attentional states influence
      evaluative response is limited by working memory capacity. Results indicated that
      individuals with schizophrenia demonstrated the typical distractor devaluation
      effect at working memory load 0, suggesting intact evaluative response. However,
      the devaluation effect was absent at working memory loads of 1 and 2, suggesting
      that normal evaluative responses can be abolished in people with schizophrenia
      when working memory capacity is exceeded. Thus, findings provide further evidence
      for normal evaluative response in schizophrenia, but clarify that these normal
      experiences may not hold when working memory demands are too high.

PMID- 22968208
TI  - Mercury-induced chromosomal damage in wild fish (Dicentrarchus labrax L.)
      reflecting aquatic contamination in contrasting seasons.
AB  - Ria de Aveiro (mainly Laranjo basin, Portugal) has been subjected to mercury
      contamination from a chlor-alkali plant, currently presenting a well-described
      mercury gradient. This study aimed to assess mercury genotoxicity in this area by
      measuring the frequency of erythrocytic nuclear abnormalities (ENA) in the
      European sea bass (Dicentrarchus labrax), addressing the relation with total
      mercury concentration in the blood and the modulatory role of seasonal variables.
      Fish were collected, in warm and cold periods, at three locations differing in
      their distances to the main mercury source: reference (R), moderately (M), and
      highly (H) contaminated sites. Genotoxicity was detected in both degrees of
      contamination (M and H) and in both periods of the year (warm and cold), which is
      in line with the greater levels of mercury measured in fish blood. No significant
      seasonal variations were observed for mercury bioaccumulation or ENA frequency.
      The apparent low imperviousness of ENA frequency to seasonal factors reinforced
      its consistency as a genotoxicity biomarker, thus enabling a clearer
      identification of cause-and-effect relationships. Overall, the results reflected
      a serious environmental risk to native ichthyofauna at Laranjo basin due to
      mercury contamination, showing a potential of mercury to induce genetic damage in
      fish blood cells through clastogenic and/or aneugenic actions.

PMID- 22968209
TI  - Early neurologic complications and long-term sequelae of childhood bacterial
      meningitis in a limited-resource country (Kosovo).
AB  - PURPOSE: Since neurologic complications of childhood bacterial meningitis are
      encountered frequently despite antibiotic treatments, the purpose of this study
      was to analyze early neurologic complications and long-term sequelae of bacterial
      meningitis in children in a limited-resource country (Kosovo) METHODS: This study
      uses a retrospective chart review of children treated for bacterial meningitis in
      two study periods: 277 treated during years 1997-2002 and 77 children treated
      during years 2009-2010. RESULTS: Of the 277 vs 77 children treated for bacterial
      meningitis, 60 (22%) vs 33 (43%) patients developed early neurologic
      complications, while there were 15 (5.4%) vs 2 (2.6%) deaths. The most frequent
      early neurologic complications were the following: subdural effusions (13 vs
      29%), recurrent seizures (11 vs 8%), and hydrocephalus (3 vs 3%). The relative
      risk (95% confidence interval) for neurologic complications was the highest in
      infants (3.56 (2.17-5.92) vs 2.69 (1.62-4.59)) and in cases caused by Haemophilus
      influenzae 1.94 (1.09-3.18) vs Streptococcus pneumoniae 2.57(1.26-4.47). Long
      term sequelae were observed in 10 vs 12% of children, predominantly in infants.
      The most frequent long-term sequelae were late seizures 9 vs 1%,
      neuropsychological impairment 1 vs 5%, and deafness 1 vs 3%. CONCLUSIONS: In both
      study periods, the most frequent early neurologic complications of childhood
      bacterial meningitis were subdural effusions. Long-term sequelae were observed in
      10% of children, with late seizures, neuropsychological impairment, and deafness
      being the most common one. Age prior to 12 months was risk factor for both early
      neurologic complications and long-term sequelae of bacterial meningitis in
      children.

PMID- 22968210
TI  - Wind instruments and headaches.
AB  - The authors illustrate the cases of two children with headaches, one diagnosed
      with Chiari type 1 malformation and the other with hydrocephalus, who played wind
      instruments. Both patients manifested that their headaches worsened with the
      efforts made during playing their musical instruments. We briefly comment on the
      probable role played by this activity on the patients' intracranial pressure and
      hypothesize that the headaches might be influenced by increases in their
      intracranial pressure related to Valsalva maneuvers. We had serious doubts on if
      we should advise our young patients about giving up playing their music
      instruments.

PMID- 22968212
TI  - Anisotropic interpolation of sparse generalized image samples.
AB  - Practical image-acquisition systems are often modeled as a continuous-domain
      prefilter followed by an ideal sampler, where generalized samples are obtained
      after convolution with the impulse response of the device. In this paper, our
      goal is to interpolate images from a given subset of such samples. We express our
      solution in the continuous domain, considering consistent resampling as a data
      fidelity constraint. To make the problem well posed and ensure edge-preserving
      solutions, we develop an efficient anisotropic regularization approach that is
      based on an improved version of the edge-enhancing anisotropic diffusion
      equation. Following variational principles, our reconstruction algorithm
      minimizes successive quadratic cost functionals. To ensure fast convergence, we
      solve the corresponding sequence of linear problems by using multigrid iterations
      that are specifically tailored to their sparse structure. We conduct illustrative
      experiments and discuss the potential of our approach both in terms of
      algorithmic design and reconstruction quality. In particular, we present results
      that use as little as 2% of the image samples.

PMID- 22968211
TI  - Relaxation in x-space magnetic particle imaging.
AB  - Magnetic particle imaging (MPI) is a new imaging modality that noninvasively
      images the spatial distribution of superparamagnetic iron oxide nanoparticles
      (SPIOs). MPI has demonstrated high contrast and zero attenuation with depth, and
      MPI promises superior safety compared to current angiography methods, X-ray,
      computed tomography, and magnetic resonance imaging angiography. Nanoparticle
      relaxation can delay the SPIO magnetization, and in this work we investigate the
      open problem of the role relaxation plays in MPI scanning and its effect on the
      image. We begin by amending the x-space theory of MPI to include nanoparticle
      relaxation effects. We then validate the amended theory with experiments from a
      Berkeley x-space relaxometer and a Berkeley x-space projection MPI scanner. Our
      theory and experimental data indicate that relaxation reduces SNR and
      asymmetrically blurs the image in the scanning direction. While relaxation
      effects can have deleterious effects on the MPI scan, we show theoretically and
      experimentally that x-space reconstruction remains robust in the presence of
      relaxation. Furthermore, the role of relaxation in x-space theory provides
      guidance as we develop methods to minimize relaxation-induced blurring. This will
      be an important future area of research for the MPI community.

PMID- 22968213
TI  - Therapeutic effects of neuregulin-1 gene transduction in rats with myocardial
      infarction.
AB  - AIM: In this study, we investigated whether lentivirus-mediated gene transduction
      improves the cardiac function in rats with myocardial infarction and the
      mechanisms involved. METHODS AND RESULTS: Briefly, lentivirus carrying human
      neuregulin-1 (hNRG-1) gene was injected into infarcted myocardium of rats. Four
      weeks later, lentivirus-mediated gene transduction promoted hNRG-1 gene and
      protein expression. Overexpression of hNRG-1 increased the number of microvessels
      in the ischemic myocardium and decreased the number of terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL)-stained positive cells.
      Furthermore, qRT-PCR assay showed that hNRG-1 was capable of increasing the
      expression of bcl-2 and VEGF-A while decreasing the expression of bax. Western
      blot analysis suggested that overexpression of hNRG-1 activated the PI3K/Akt
      pathway and increased the phosphorylation of Akt and eNOS. CONCLUSION: These
      findings suggest that NRG-1 gene transduction can improve cardiac function by
      promoting angiogenesis and preventing apoptosis.

PMID- 22968214
TI  - Delayed versus immediate stenting for the treatment of ST-elevation acute
      myocardial infarction with a high thrombus burden.
AB  - OBJECTIVES: High thrombus burden (HTB) is an independent predictor of no flow or
      low reflow during a primary percutaneous coronary intervention. This study aimed
      to compare immediate versus delayed stenting in ST-elevation myocardial
      infarction (STEMI) patients with HTB. METHODS: In this retrospective,
      nonrandomized study, a total of 103 consecutive STEMI patients with HTB (thrombus
      burden score, TBS>=3) were assigned to immediate stenting (IS group, n=50) or
      delayed stenting (DS group, n=53), a decision that was made at the discretion of
      the operators. The IS group received stent placement immediately, whereas the DS
      group was given enhanced antithrombotic therapies and deferred for stenting at
      least 7 days later. Thrombolysis in myocardial infarction (TIMI) flow score
      (TIMIs) and myocardial blush grade (MBG) were assessed angiographically and the
      left ventricular ejection fraction (LVEF) was measured echocardiographically. The
      major adverse cardiac event (MACE) was the composite of cardiac death,
      reinfarction, target vessel revascularization, heart failure, and major bleeding.
      RESULTS: The DS group had better immediate MBG (P<0.001), higher LVEF at 6 months
      (P=0.044), and lower MACE rate at 1 year (log-rank P=0.008). Multiple logistic
      regression identified immediate stenting (odds ratio 7.4, 95% confidence interval
      2.1-26.6; P=0.002) and high TBS (odds ratio 2.6, 95% confidence interval 1.1-6.5,
      P=0.034) as the independent predictors of poor myocardial perfusion. Delayed
      stenting benefited the male patients, those who were of a younger age, and those
      who had a larger infarction-related artery, higher TBS, or lower TIMIs in terms
      of MBG or MACE. Delayed stenting avoided stent implantation of the infarct
      related artery in 12/53 (22.6%) patients particularly in the younger patients.
      CONCLUSION: For STEMI patients with HTB who have undergone initial thrombectomy,
      delayed stenting is safe and feasible, and may be associated with better
      immediate myocardial perfusion, more LV function recovery, and less occurrence of
      MACE at the 1-year follow-up.

PMID- 22968215
TI  - SYNTAX score:  an independent predictor of long-term cardiac mortality in
      patients with acute ST-elevation myocardial infarction.
AB  - INTRODUCTION: This observational study aimed to determine whether the SYNergy
      between percutaneous coronary intervention (PCI) with TAXUS drug-eluting stent
      and the cardiac surgery (SYNTAX) score can act as an independent predictor for
      cardiac death on long-term follow-up in patients with acute ST-elevation
      myocardial infarction (STEMI). METHODS: One hundred and fifty-three patients
      admitted to the Chang Gung Memorial Hospital in Linkou because of acute STEMI
      from 1 January 2008 to 31 December 2009, who subsequently underwent a primary
      PCI, were included in this study. SYNTAX scores were calculated immediately after
      the primary PCI; and the prognostic value of the SYNTAX score in relation to
      cardiovascular events, which were defined as low-risk (SYNTAX score 0-22) and
      intermediate-risk to high-risk (SYNTAX score>22), was determined. Long-term
      follow-up was available in 141 patients (92%, mean follow-up duration of 30+/-11
      months). RESULTS: By Kaplan-Meier estimates, cardiac death-free survival was
      99.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group
      at 42 months of follow-up (P<0.001). For all-cause death, the survival rate was
      93.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group
      at 42 months of follow-up (P=0.002). Multivariate Cox-regression analysis showed
      that independent predictors of cardiac death were the SYNTAX score (odds ratio
      15.90; 95% confidence interval 1.04-244.21) and symptom to onset-to-therapy
      interval (odds ratio 25.57; 95% confidence interval 1.00-655.96). CONCLUSION: The
      SYNTAX score is a strong independent predictor of cardiac death in intermediate
      risk to high-risk patients with acute STEMI.

PMID- 22968216
TI  - Severity and prognostic localization of critical coronary artery stenoses: 
      correlation with clinical control of major traditional risk factors.
AB  - PURPOSE: To evaluate the association between the severity and angiographic
      localization of coronary artery stenoses and clinical control of major
      traditional risk factors (RF). METHODS: We analyzed 500 patients without known
      cardiovascular disease, undergoing coronary angiography for the diagnosis of
      coronary artery disease (CAD), with one or more major traditional RF, all in
      optimal clinical control. For the quantitative evaluation of CAD, we used a
      vessel and stenosis score to evaluate the severity of CAD. Moreover, we defined
      the prognostic localization of CAD as a critical stenosis (>=50%) of the left
      main (LM) and/or the proximal segment of the left anterior descending coronary
      artery (LAD). RESULTS: The presence of RF was as follows: one in 14.2%, two in
      40.6%, three in 35%, and more than three in 10.2% of the patients. Prognostic
      localization of critical stenosis on the proximal segment of LAD and/or LM was
      found in 174 patients (34.8%). The severity of CAD and prognostic localization of
      critical stenosis was not correlated with all of the conventional RF evaluated or
      their association (P>0.05). CONCLUSION: In this population with optimally
      controlled traditional RF, the severity of CAD or prognostic localization on LM
      and/or proximal LAD was not correlated with the major RF analyzed.

PMID- 22968217
TI  - Understanding and managing interferon-alpha-related fatigue in patients with
      melanoma.
AB  - Fatigue is the most common toxicity associated with adjuvant interferon-alpha
      treatment of melanoma, with an incidence ranging from 80 to 90%. It may be dose
      limiting and may lead to treatment discontinuation in a large proportion of
      patients. Fatigue is commonly diagnosed by self-report, does not have a precise
      definition, and has a high degree of overlap with symptoms of depression.
      Specific fatigue scales have been developed over the past few years, assessing
      fatigue either one-dimensionally or multi-dimensionally. However, the
      characteristics that define an accurate and efficient fatigue scale have not been
      established. Despite the debilitating effects of fatigue resulting from
      interferon treatment, a large proportion of patients place a higher value on the
      relapse-free survival benefits of treatment compared with quality-of-life
      deterioration. Pharmacologic interventions to treat and manage fatigue are not
      well established, although psychostimulants are sometimes used. We recommend
      incorporating structure and routine into day-to-day activities to cope with
      fatigue. In our experience, participating in moderate physical activities and
      drinking sufficient fluids are key factors to ensuring efficient fatigue
      management. A multidisciplinary team is necessary to translate the fatigue
      management recommendations into practice. Clinical trials using appropriate
      fatigue assessment tools to investigate interventional therapies are warranted.
      We recommend the use of the cross-culturally European Organisation for Research
      and Treatment of Cancer quality-of-life questionnaire Fatigue Module FA13 for
      clinical trials as well as in day-to-day clinical trials.

PMID- 22968218
TI  - Hispanic acculturation, psychosocial functioning, and routine support for
      diabetes self-management.
AB  - PURPOSE: The purpose of this study was to describe the relationship between
      Spanish language-based acculturation, psychosocial coping with diabetes, and
      perceptions of social support obtainment for the daily management of diabetes.
      METHODS: Adults (N = 209) were surveyed by telephone about Hispanic ethnicity,
      depressed mood (PHQ-8), anxiety and worry over diabetes, social burden due to
      diabetes, diabetes control, and physical function (Diabetes-39), and Spanish
      language-based acculturation (n = 101, Hispanic only). RESULTS: Significant
      associations revealed a relationship between less language-based acculturation
      with other contextual factors (gender, family demands, disease severity), and
      depressed mood and social burden of disease. Acculturation alone explained little
      about psychosocial coping. Individuals with poor psychosocial coping were more
      likely to have routine daily help with diabetes self- management, with
      acculturation explaining little about who obtains help. CONCLUSIONS: Hispanic
      values such as placing a priority on providing help to friends and family likely
      have more to do with psychosocial coping with diabetes than does language
      preference or proficiency. Individuals with poor psychosocial functioning may
      benefit from external social support when family support is not present to help
      with the routine management of diabetes.

PMID- 22968219
TI  - En Balance: the effects of Spanish diabetes education on physical activity
      changes and diabetes control.
AB  - PURPOSE: This study was designed to assess the feasibility of culturally and
      language-sensitive diabetes education as a way to increase physical activity and
      to improve health/diabetes management in a group of Spanish-speaking Hispanics in
      the Inland Empire region of Southern California. METHODS: En Balance is a
      culturally sensitive diabetes education program designed for Spanish-speaking
      Hispanic adults. The 3-month educational intervention assessed 16 males and 23
      females living in Riverside and San Bernardino counties of Southern California.
      Baseline and 3-month evaluations of physical activity were assessed using the
      validated Arizona Activity Frequency Questionnaire. RESULTS: After 3 months on
      the En Balance program, there was a significant increase in moderate intensity
      physical activity energy expenditure (M = 368 +/- 894 kcal/day, P < 0.01) and
      high intensity physical activity energy expenditure (M = 405 +/- 2569 kcal/day, P
      = 0.05) compared to baseline and significant reductions in A1C (-0.90%, P =
      0.01), total cholesterol (-13.44 mg/dl, P = 0.01), LDL cholesterol (-10.28 mg/dl,
      P = 0.03), and waist circumference (-1.52 cm, P = 0.04). CONCLUSION: En Balance
      program resulted in significant mean increases in both moderate and high
      intensity physical activity energy expenditure among this group of Hispanic
      diabetic participants, indicating that despite a general pattern of low physical
      activity in this group, an intervention that stresses both nutrition and exercise
      in culturally sensitive ways can positively impact participant's physical
      activity levels as well as impact nutritional changes.

PMID- 22968220
TI  - Two-year results of translating the diabetes prevention program into an urban,
      underserved community.
AB  - PURPOSE: The purpose of the study was to examine the long-term effect of a Group
      Lifestyle Balance (GLB) program on weight, impaired fasting glucose,
      hypertension, and hyperlipidemia in an urban, medically underserved community.
      METHODS: This study was a single-arm prospective intervention study that was
      designed to test the effectiveness of a community-based GLB intervention. In sum,
      638 residents from 11 targeted neighborhoods were screened for body mass index >=
      25 kg/m(2) and metabolic syndrome. Eligible individuals took part in a 12-week
      GLB intervention (n = 105) that addressed weight loss and physical activity.
      Subjects were followed for 24 months. RESULTS: The probability of being at risk
      for diabetes and cardiovascular disease was significantly reduced by 25.7% over
      the long-term follow-up. Of the participants who lost at least 5% of their body
      weight following the intervention, 52.6% maintained the 5% weight loss at their
      last follow-up time, weighing about 20 lb less than they did at baseline.
      CONCLUSION: Risk reduction and weight loss maintenance are possible following a
      GLB intervention and have substantial potential for future public health impact.

PMID- 22968221
TI  - A graphene-based multifunctional affinity probe for selective capture and
      sequential identification of different biomarkers from biosamples.
AB  - A novel multifunctional graphene-based affinity probe has been explored for
      selective capture of two different types of peptides from the biosamples for
      sequential detection.

PMID- 22968222
TI  - Indirect genetic effects and the genetic bases of social dominance: evidence from
      cattle.
AB  - Genetic studies of social behaviour have currently received new impetus from
      models including indirect genetic effects (IGEs) of social partners. This study
      aimed at investigating the contribution of conspecifics in social dominance,
      considered as response of dyadic interaction that is, winning (dominant
      individual) or losing (subordinate). A genetic correlation of -1 is expected
      between the attitude to win and the attitude to loose, and because a population
      always accounts for half winners and half losers, the heritability of the
      dominant status should be close to zero. Specifically, social dominance was
      studied in Aosta Chestnut and Aosta Black Pied (Bos taurus) breeds, alpine rustic
      cattle famous for traditional tournaments where pairs of cows assess dominant
      status in bloodless fights. The outcomes of 25,590 dyadic interactions performed
      by 8159 individuals in 11 years were analysed by applying a classical
      quantitative model and models including indirect effects. Data were analysed via
      Bayesian approach on a threshold trait. The assessment of variances revealed a
      genetic correlation of -0.976 between direct and indirect genetic components. The
      heritability measured on a liability scale was 0.122 for direct phenotype, but
      decreased to 0.014 when the total heritable variance (TBV) was considered. The
      trend of estimated breeding values showed that the total TBV was constant over
      the years, even though its direct component increased and the indirect part
      decreased. This result confirms the relevance of IGEs on social behaviour and the
      assumption that the mean individual social dominance cannot evolve within a
      population, due to the evolutionary constraints imposed by the 'social
      environment'.

PMID- 22968223
TI  - Solute-solvent hydrogen-bonding in room temperature ionic liquids studied by
      Raman spectroscopy.
AB  - The vibrational frequencies of the C=O + C=C band of diphenylcyclopropenone and
      the NH(2) stretching band of p-aminobenzonitrile were determined in various room
      temperature ionic liquids (RTILs). The vibrational frequency shifts of the C=O +
      C=C stretching mode were compared with Kamlet alpha values, and frequency shifts
      of the NH(2) stretching mode were compared with Kamlet beta values. A nearly
      linear relationship was obtained for both parameters, although the solvatochromic
      parameters were more sensitive to changes of the cation species. Vibrational
      frequency calculations of a 1 : 1 cluster of p-aminobenzonitrile with the RTIL
      anions using DFT theory reproduced the observed frequency shifts of the NH(2)
      stretching mode fairly well. The frequency shifts of the CN stretching mode were
      well reproduced by the linear combination of dipolarity parameters, the hydrogen
      bond donating and accepting parameters determined by the Raman shift of the
      solute molecule.

PMID- 22968224
TI  - MARS: a mouse atlas registration system based on a planar x-ray projector and an
      optical camera.
AB  - This paper introduces a mouse atlas registration system (MARS), composed of a
      stationary top-view x-ray projector and a side-view optical camera, coupled to a
      mouse atlas registration algorithm. This system uses the x-ray and optical images
      to guide a fully automatic co-registration of a mouse atlas with each subject, in
      order to provide anatomical reference for small animal molecular imaging systems
      such as positron emission tomography (PET). To facilitate the registration, a
      statistical atlas that accounts for inter-subject anatomical variations was
      constructed based on 83 organ-labeled mouse micro-computed tomography (CT)
      images. The statistical shape model and conditional Gaussian model techniques
      were used to register the atlas with the x-ray image and optical photo. The
      accuracy of the atlas registration was evaluated by comparing the registered
      atlas with the organ-labeled micro-CT images of the test subjects. The results
      showed excellent registration accuracy of the whole-body region, and good
      accuracy for the brain, liver, heart, lungs and kidneys. In its implementation,
      the MARS was integrated with a preclinical PET scanner to deliver combined
      PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical
      PET images.

PMID- 22968225
TI  - Investigation of energy gene expressions and community structures of free and
      attached acidophilic bacteria in chalcopyrite bioleaching.
AB  - In order to better understand the bioleaching mechanism, expression of genes
      involved in energy conservation and community structure of free and attached
      acidophilic bacteria in chalcopyrite bioleaching were investigated. Using
      quantitative real-time PCR, we studied the expression of genes involved in energy
      conservation in free and attached Acidithiobacillus ferrooxidans during
      bioleaching of chalcopyrite. Sulfur oxidation genes of attached A. ferrooxidans
      were up-regulated while ferrous iron oxidation genes were down-regulated compared
      with free A. ferrooxidans in the solution. The up-regulation may be induced by
      elemental sulfur on the mineral surface. This conclusion was supported by the
      results of HPLC analysis. Sulfur-oxidizing Acidithiobacillus thiooxidans and
      ferrous-oxidizing Leptospirillum ferrooxidans were the members of the mixed
      culture in chalcopyrite bioleaching. Study of the community structure of free and
      attached bacteria showed that A. thiooxidans dominated the attached bacteria
      while L. ferrooxidans dominated the free bacteria. With respect to available
      energy sources during bioleaching of chalcopyrite, sulfur-oxidizers tend to be on
      the mineral surfaces whereas ferrous iron-oxidizers tend to be suspended in the
      aqueous phase. Taken together, these results indicate that the main role of
      attached acidophilic bacteria was to oxidize elemental sulfur and dissolution of
      chalcopyrite involved chiefly an indirect bioleaching mechanism.

PMID- 22968227
TI  - A longitudinal pilot proton MRS investigation of the manic and euthymic states of
      bipolar disorder.
AB  - Several lines of evidence implicate dysfunction in brain energy production as a
      key component of bipolar disorder. In particular, elevated brain lactate levels
      observed in this condition suggest a shift from aerobic to anaerobic metabolism,
      possibly as a result of mitochondrial abnormalities. Most prior imaging studies
      of brain metabolites were performed in either euthymic or depressed bipolar
      patients or compared different populations in different mood states. We sought to
      measure brain metabolite concentrations in the same patients in both manic and
      euthymic states. Given the dramatic changes in clinical state of bipolar disorder
      patients, we hypothesized that previously observed abnormalities in lactate
      concentrations in bipolar disorder might show state dependent changes. In this
      study 15 patients (mean age 36.1 years) diagnosed with bipolar I disorder
      underwent proton magnetic resonance spectroscopy of the anterior cingulate cortex
      and parieto-occipital cortex during hospitalization for acute mania (mean Young
      Mania Rating Scale (YMRS) 22.1). Seven of these subjects returned (mean interval
      21.16 months) to have imaging repeated while euthymic (mean YMRS 2.0). A group of
      age- and gender-matched control participants (N=6) were scanned as well. We
      report that during mania, bipolar disorder subjects had lactate levels comparable
      to healthy control subjects but during euthymia these levels were significantly
      reduced. No significant change was observed for other metabolites. These results
      implicate mood dependent alterations in energy metabolism in the biology of
      bipolar disorder. Additionally, this finding has potential use as a biomarker for
      both evaluating novel treatments as well as diagnostic clarification between mood
      disorders.

PMID- 22968228
TI  - Cation exchange on the nanoscale: an emerging technique for new material
      synthesis, device fabrication, and chemical sensing.
AB  - Cation exchange is an age-old technique for the chemical conversion of liquids or
      extended solids by place-exchanging the cations in an ionic material with a
      different set of cations. The technique is undergoing a major revival with the
      advent of high-quality nanocrystals: researchers are now able to overcome the
      limitations in bulk systems and fully exploit cation exchange for materials
      synthesis and discovery via rapid, low-temperature transformations in the solid
      state. In this tutorial review, we discuss cation exchange as a promising
      materials synthesis and discovery tool. Exchange on the nanoscale exhibits some
      unique attributes: rapid kinetics at room temperature (orders of magnitude faster
      than in the bulk) and the tuning of reactivity via control of nanocrystal size,
      shape, and surface faceting. These features make cation exchange a convenient
      tool for accessing nanocrystal compositions and morphologies for which
      conventional synthesis may not be established. A simple exchange reaction allows
      extension of nanochemistry to a larger part of the periodic table, beyond the
      typical gamut of II-VI, IV-VI, and III-V materials. Cation exchange
      transformations in nanocrystals can be topotactic and size- and shape-conserving,
      allowing nanocrystals synthesized by conventional methods to be used as templates
      for production of compositionally novel, multicomponent, or doped nanocrystals.
      Since phases and compositions resulting from an exchange reaction can be
      kinetically controlled, rather than governed by the phase diagram, nanocrystals
      of metastable and hitherto inaccessible compositions are attainable. Outside of
      materials synthesis, applications for cation exchange exist in water
      purification, chemical staining, and sensing. Since nanoscale cation exchange
      occurs rapidly at room temperature, it can be integrated with sensitive
      environments such as those in biological systems. Cation exchange is already
      allowing access to a variety of new materials and processes. With better
      mechanistic understanding and control, researchers may be able to advance the
      field to a stage where a custom nanostructure of arbitrary complexity would be
      achievable by simple cation exchange chemistry and a basic understanding of the
      periodic table.

PMID- 22968229
TI  - Correlation between lead levels in drinking water and mothers' breast milk:
      Dakahlia, Egypt.
AB  - This study was performed on fifty-two drinking tap water samples (surface and
      groundwater) collected from different districts of Dakahlia Governorate and fifty
      two breast milk samples from lactating mothers hosted in Dakahlia Governorate
      hospitals. All these samples were subjected to lead analysis. Lead level in
      drinking groundwater showed higher levels than in drinking surface water. Also,
      an elevation of lead levels in breast milk of mothers drinking groundwater was
      noticed when compared with that of mothers drinking surface water. The comparison
      between mean lead levels in drinking water and mothers' breast milk samples
      showed positive relationship. Lead concentrations in breast milk of the studied
      samples were elevated by exposure to smoking. We conclude that prolonged contact
      with lead plumbing can increase the lead content in tap water with subsequent
      increase in lead burden in infant fed formula and infant blood. Also, we
      recommend that chemical analyses must be carried out periodically for the surface
      and groundwater to ensure the water suitability for drinking purposes. Passive
      exposure to smoking during lactation should be avoided. Capsule: Prolonged
      contact with lead plumbing can increase the lead content in tap water with
      subsequent increase in lead burden in infant fed formula and infant blood.

PMID- 22968230
TI  - Synthesis of highly active Pt-CeO2 hybrids with tunable secondary nanostructures
      for the catalytic hydrolysis of ammonia borane.
AB  - We demonstrate a fast and facile ultrasound-assisted method to fabricate Pt
      CeO(2) hybrids with tunable secondary nanostructures. The influence of hybrid
      structures towards their catalytic properties has been studied in depth. As a
      result the Pt-CeO(2) nanonecklace shows better catalytic performance than the
      nanoflower and the nanosatellite.

PMID- 22968231
TI  - Festival foods in the immigrant diet.
AB  - Dietary acculturation for immigrant groups has largely been attributed to the
      "Westernization" of indigenous diets, as characterized by an increased
      consumption of unhealthy American foods (i.e., fast foods, hamburgers). However,
      acculturation and adoption of western dietary habits may not fully explain new
      dietary patterns among racial/ethnic minority immigrants. The immigrant diet may
      change in such a way that it elaborates on specific ethnic traditions in addition
      to the incorporation of Western food habits. In this paper, we explore the role
      that festival foods, those foods that were once eaten a few times a year and on
      special occasions, play in the regular diet of immigrants to the US. This paper
      will focus on the overconsumption of ethnic festival foods, which are often high
      in carbohydrates, animal protein, sugar and fat, as opposed to Western "junk"
      food, as an explanation for the increased risk of cardiometabolic disorders among
      new immigrant groups. 

PMID- 22968234
TI  - Facile bottom-up synthesis of graphene nanofragments and nanoribbons by thermal
      polymerization of pentacenes.
AB  - To prepare nanosized graphene-like molecules of a defined structure (defined
      width graphene nanoribbons or nanofragments) by a simple bottom-up method,
      thermal polymerization reactions of pentacenes were investigated. By optimizing
      heat treatment temperature and initial precursor weight, long-length fused
      pentacene molecules were successfully obtained at least up to octamer (n = 8).
      Here, the degree of polymerization was much larger than that of previously known
      polymerized pentacene systems (n = 2, 3). The structural and physical properties
      of the obtained fused pentacenes were characterized by Raman spectroscopy, X-ray
      diffraction, and photoluminescent spectroscopy. The fused pentacene system,
      examined using density functional theory calculations, was found to have unique
      electronic and magnetic structures originating from its characteristic size and
      edge structure. In addition, we performed detailed mass spectroscopic analysis
      that examined the fusing mechanism.

PMID- 22968235
TI  - Safe surgery--a cornestone of quality.

PMID- 22968232
TI  - Outcome of pregnancy in patients with structural or ischaemic heart disease:
      results of a registry of the European Society of Cardiology.
AB  - AIMS: To describe the outcome of pregnancy in patients with structural or
      ischaemic heart disease. METHODS AND RESULTS: In 2007, the European Registry on
      Pregnancy and Heart disease was initiated by the European Society of Cardiology.
      Consecutive patients with valvular heart disease, congenital heart disease,
      ischaemic heart disease (IHD), or cardiomyopathy (CMP) presenting with pregnancy
      were enrolled. Data for the normal population were derived from the literature.
      Sixty hospitals in 28 countries enrolled 1321 pregnant women between 2007 and
      2011. Median maternal age was 30 years (range 16-53). Most patients were in NYHA
      class I (72%). Congenital heart disease (66%) was most prevalent, followed by
      valvular heart disease 25%, CMP 7%, and IHD in 2%. Maternal death occurred in 1%,
      compared with 0.007% in the normal population. Highest maternal mortality was
      found in patients with CMP. During pregnancy, 338 patients (26%) were
      hospitalized, 133 for heart failure. Caesarean section was performed in 41%.
      Foetal mortality occurred in 1.7% and neonatal mortality in 0.6%, both higher
      than in the normal population. Median duration of pregnancy was 38 weeks (range
      24-42) and median birth weight 3010 g (range 300-4850). In centres of developing
      countries, maternal and foetal mortality was higher than in centres of developed
      countries (3.9 vs. 0.6%, P < 0.001 and 6.5 vs. 0.9% P < 0.001) CONCLUSION: The
      vast majority of patients can go safely through pregnancy and delivery as long as
      adequate pre-pregnancy evaluation and specialized high-quality care during
      pregnancy and delivery are available. Pregnancy outcomes were markedly worse in
      patients with CMP and in developing countries.

PMID- 22968233
TI  - Viral-bacterial interactions in acute otitis media.
AB  - Acute otitis media (AOM) is a polymicrobial disease, which usually occurs as a
      complication of viral upper respiratory tract infection (URI). While respiratory
      viruses alone may cause viral AOM, they increase the risk of bacterial middle ear
      infection and worsen clinical outcomes of bacterial AOM. URI viruses alter
      Eustachian tube (ET) function via decreased mucociliary action, altered mucus
      secretion and increased expression of inflammatory mediators among other
      mechanisms. Transient reduction in protective functions of the ET allows
      colonizing bacteria of the nasopharynx to ascend into the middle ear and cause
      AOM. Advances in research help us to better understand the host responses to
      viral URI, the mechanisms of viral-bacterial interactions in the nasopharynx and
      the development of AOM. In this review, we present current knowledge regarding
      viral-bacterial interactions in the pathogenesis and clinical course of AOM. We
      focus on the common respiratory viruses and their established role in AOM.

PMID- 22968236
TI  - Nasoenteric tube complications.
AB  - The use of nasoenteric tubes (NETs) is ubiquitous, and clinicians often take
      their placement, function, and maintenance for granted. NETs are used for
      gastrointestinal decompression, enteral feeding, medication administration, naso
      biliary drainage, and specialized indications such as upper gastrointestinal
      bleeding. Morbidity associated with NETs is common, but frequently subtle,
      mandating high index of suspicion, clinical vigilance, and patient safety
      protocols. Common complications include sinusitis, sore throat and epistaxis.
      More serious complications include luminal perforation, pulmonary injury,
      aspiration, and intracranial placement. Frequent monitoring and continual re
      review of the indications for continued use of any NET is prudent, including
      consideration of changing goals of care. This manuscript reviews NET-related
      complications and associated topics.

PMID- 22968237
TI  - Distal pancreatectomy using a no-touch isolation technique.
AB  - BACKGROUND AND AIMS: Distal pancreatectomy is the only effective treatment for
      cancers of the pancreatic body and tail. The recurrence rate after DP has
      remained high. In an effort to over-come this problem, we developed a no-touch
      surgical technique for DP. This is a pilot study to see if distal pancreatectomy
      can be technically done using a no-touch surgical technique with-out
      deteriorating the post-operative prognosis. PATIENTS AND METHODS: From November
      2000 through May 2011, 16 pancreatic ductal adeno-carcinoma patients have been
      operated on using a no-touch technique by a single operator. We described the
      surgical technique, and we reported our preliminary experience. During the
      procedure, the pancreatic body and tail is neither grasped nor squeezed by the
      surgeon. And all drainage vessels from the pancreatic body and tail are ligated
      and divided during the early phase of the operation. Furthermore, for improved
      dissection of the retroperitoneal tissue (rightward and posterior margins), we
      use a hanging and clamping maneuver and dissection behind Gerota's fascia.
      RESULTS: In the current series, the posterior and rightward resection margins
      were free in all patients, although seven were positive for anterior serosal
      invasion. The post-operative prognosis was not deteriorated with this technique.
      CONCLUSION: No-touch distal pancreatectomy technique may have some theoretical
      advantages, which merit future investigation in randomized controlled trials.

PMID- 22968238
TI  - Synchronous pulmonary metastases from renal cell carcinoma--a whole nation study
      on prevalence and potential resectability.
AB  - BACKGROUND: At the time of diagnosis, almost one third of patients with renal
      cell carcinoma (RCC) have metastasis. We studied the prevalence, survival, and
      potential resectability of synchronous pulmonary metastases (SPMs) in a well
      defined cohort of RCC patients. MATERIAL AND METHODS: A retrospective whole
      nation study including RCC patients with SPM diagnosed 1970-2005 in Iceland.
      Imaging studies and histology were reviewed, the TNM system used for staging the
      primary tumors, and disease-specific survival estimated. Eligibility for SPM
      removal was evaluated using different criteria from the literature on surgical
      management of SPM, including solitary SPM and SPMs confined to one lung. RESULTS:
      Altogether, 154 patients (16.9%) had SPMs. In 55 of these patients (35.7%) the
      lungs were the only site, with detailed information available in 46 cases. Of
      these 46 patients with SPMs, 15 were unilateral, and of those 11 were solitary.
      All of these 11 patients were in good physical condition and were deemed eligible
      for surgical resection; however, only one of them was operated with
      metastasectomy. Disease-specific survival at five years for patients with
      solitary SPM was 27.2%, as compared to 12.7%, 7.1%, and 12.0% for patients with
      unilateral SPMs, all patients with SPMs, and patients with extrapulmonal
      metastases, respectively (p = 0.33). CONCLUSION: At the time of diagnosis, 16.9%
      of RCC patients had SPM. In one in three of these SPM patients metastases were
      confined to the lungs, while one in five had solitary pulmonary metastases.
      Although the benefit of pulmonary metastasectomy in RCC is still debated and
      criteria for resection are not well defined, it appears that many RCC patients
      with SPM are potentially eligible for pulmonary metastasectomy.

PMID- 22968239
TI  - Incidence and outcomes of surgical resection for giant pulmonary bullae--a
      population-based study.
AB  - BACKGROUND: Giant pulmonary bullae (GPB) are rare and there is little information
      on incidence, long-term prognosis, and outcome of treatment. OBJECTIVES: To
      assess the incidence of GPB in the Icelandic population and to evaluate the
      outcome of surgical treatment. METHODS: Twelve consecutive patients (11 males;
      mean age 60 +/- 15.7 years) underwent resection for GPB in Iceland between 1992
      and 2009. All were heavy smokers and had bullae occupying > 30% of the involved
      lung. There were 8 bilateral and 3 unilateral bullectomies and one lobectomy.
      Pulmonary function tests were performed preoperatively, and at one month and 5.4
      years postoperatively. Age-standardized incidence rate (ASR) was calculated,
      complications and operative mortality were registered, and overall survival was
      estimated. Mean follow-up time was 8.2 years. RESULTS: The ASR for GPB was 0.40
      and 0.03 per 100,000 per year for men and women, respectively. There was no
      operative mortality, but prolonged air leakage (75%) and pneumonia (17%) were the
      most common postoperative complications. One month postoperatively, mean FEV1
      increased from 1.0 +/- 0.48 L (33% predicted) to 1.75 +/- 0.75 L (57.5%
      predicted) (p < 0.01), but FVC remained unchanged. RV decreased from 3.9 +/- 0.8
      L (177% predicted) to 3.0 +/- 1.0 L (128% predicted) (p < 0.05), but TLC and DLCO
      did not change after operation. At long-term follow-up the FEV1 and FVC had
      declined to near-baseline values. Five-year and 10-year survival were 100% and
      60%, respectively. CONCLUSIONS: The ASR of GPB in Iceland was 0.21 per 100,000
      per year. In this small series, bullectomy was found to be a safe procedure that
      significantly improved pulmonary function. The functional improvement then
      declined over time. Prolonged air leakage was a common postoperative complication
      that prolonged hospital stay.

PMID- 22968240
TI  - Predictors of failure of endovascular revascularization for critical limb
      ischemia.
AB  - BACKGROUND AND AIMS: To characterize predictors of failure when treating critical
      limb ischemia (CLI) patients with an endovascular intervention as the first-line
      strategy. PATIENTS AND METHODS: This retrospective, registry-based study included
      217 consecutive patients with 240 chronic critically ischemic limbs treated with
      infrainguinal percutaneous trans-luminal angioplasty (PTA) during 2006-2007 at
      Helsinki University Central Hospital, Finland. The primary outcome measures were
      death, major (above-ankle) amputation, and the need for surgical re-intervention
      within 6 months after the primary procedure. The secondary out-come measures were
      overall major amputation and survival rates as well as the overall need for
      surgical or any other (surgical or endovascular) type of re-intervention.
      Predictors of outcome endpoints were identified with a univariate screen, and a
      Cox regression model was used in the multivariate analysis. RESULTS: Compared to
      ulcer, gangrene was significantly more strongly associated with amputation within
      6 months post-procedurally as well as during the whole follow-up period (p <=
      0.028). The patient's inability to walk upon hospital arrival was a significant
      predictor of death, amputation and surgical re-intervention. Mediasclerotic ankle
      brachial index (ABI) was an independent predictor of amputation as well as
      endovascular re-interventions. CONCLUSIONS: The strong predictors of poor outcome
      after endovascular revascularization for patients with CLI are cardiac morbidity,
      the inability to ambulate upon hospital arrival, and gangrene as a manifestation
      of CLI. The risk of amputation seems to be significantly higher for gangrene than
      for ulcer and this matter should be taken into account in the clinical
      classifications for CLI.

PMID- 22968241
TI  - Gender differences in outcome after stent treatment of lesions in the
      femoropopliteal segment.
AB  - BACKGROUND AND AIMS: Although endovascular stent treatment is increasingly used
      in infrainguinal atherosclerotic occlusive disease, outcome with focus on gender
      differences has not been reported in detail. MATERIAL AND METHODS: One hundred
      and twelve consecutive patients (67 [60%]) women, undergoing endovascular nitinol
      stent treatment of atherosclerotic lesions in the femoropopliteal segment were
      analysed concerning improvement in ankle brachial index (ABI), reinterventions,
      complications, amputation and survival rates up to 12 months after intervention.
      Risk factors for amputation and death were analyzed with logistic regression.
      RESULTS: At presentation, women showed critical limb ischemia (CLI) more often
      than men (87% vs. 58 %; P = 0.001). After 12 months ABI had improved (from 0.40
      +/- 0.26 at baseline to 0.86 +/- 0.22 after 12 months, P < 0.001), but 16
      patients (15%) had been amputated and 27 patients (24 %) had died. After
      adjustment for age, diabetes mellitus and smoking, female gender was an
      independent risk factor for amputation (OR 9.0; 95% CI 1.1-76.5; P = 0.045).
      CONCLUSIONS: Stent treatment of lesions in the femoropopliteal segment had
      favourable effects on ABI and limb salvage. Treated women more often had CLI and
      ran a higher risk for amputation within 12 months than men. This might reflect
      failure of clinicians to adequately appreciate symptoms of atherosclerotic leg
      artery disease in women.

PMID- 22968242
TI  - Perioperative morbidity, mortality and early outcome of the first 360 gastric
      bypass operations performed in a district hospital.
AB  - BACKGROUND AND AIMS: We report the results for the first consecutive 360 Roux-en
      Y gastric by-pass (RYGB) operations performed in a district hospital in Finland.
      MATERIAL AND METHODS: Demographic data, perioperative characteristics, and follow
      up data were entered prospectively in the hospital's database for bariatric
      patients. RESULTS: We performed 325 primary laparoscopic Roux-en-Y gastric bypass
      (LRYGB) operations, one open RYGB, and 34 revisions. Mean BMI before the
      operations was 47.5 +/- 7.8 kg/m2 (31.5-91.0 kg/m2). The percentage of patients
      with type 2 diabetes mellitus (T2DM) was high; 52.3% (170 patients). The mean
      operative time decreased from 110 minutes during the first 108 operations to 82
      minutes for the second 108 operations, and to 74 minutes for the last 109
      operations (P < 0.001). Postoperative hospital stay was significantly reduced (P
      < 0.001) for the last 109 patients compared to the first and second group of
      patients. Overall morbidity averaged 19.1% (62/325). Severe complications were
      detected in 15 patients (4.6%). There was a tendency to more serious
      complications in the first group of patients. There was one death (mortality
      0.3%). With a follow-up rate of 97% at 3 months T2DM had resolved in 48.2%, and
      had resolved or improved in a minimum of 92.9% of the diabetic patients. Weight
      loss (WL) and excess weight loss (EWL) averaged 20% and 46% respectively.
      CONCLUSIONS: Operative time and postoperative hospital stay decrease
      significantly with increasing experience. The first one hundred patients may be
      at higher risk for complications. LRYGB operations may have an important impact
      on the resolution of T2DM in the operated population.

PMID- 22968243
TI  - Budget impact analysis of surgical treatment for obesity in Sweden.
AB  - BACKGROUND: The recent substantial increase in the number of obese surgeries
      performed in Sweden has raised concerns about the budget impact. OBJECTIVE: Our
      aim in this paper is to present an assessment of the budgetary impact of
      different policies for surgical intervention for obese and overweight subjects
      from a healthcare perspective in Sweden. METHODS: The model simulates the annual
      expected treatment costs of obesity related diseases and surgery in patients of
      different sex, age and Body Mass Index (BMI). Costs evaluated are costs of
      surgery plus the excess treatment costs that an obese patient has over and above
      the treatment costs of a normal-weight patient. The diagnoses that are included
      for costs assessment are diabetes and cardiovascular disease since these
      diagnoses are the principal diagnoses associated with obesity. Four different
      scenarios over the number of surgical operations performed each year are
      simulated and compared: (1) no surgical operation, (2) 3 000 surgical operations
      in persons with BMI > 40, (3) 4 000 (BMI > 40), and (4) 5 000 (expanded to BMI >
      38). RESULTS: Comparing Scenario 2 with Scenario 1 results in a net budget impact
      of on average SEK 121 million per annum or SEK 40 000 per patient. This implies
      that 55 percent of the cost of surgery, set equal to SEK 90 000 for each patient,
      has been offset by a reduction in the excess treatment costs of obesity related
      diseases. Expanding annual surgery from 3000 to 4000 the cost-offset increased to
      58%. By expanding annual surgery further from 4000 to 5000 and at the same time
      expanding the indication for surgery from BMI > 40 to BMI > 38, no cost-offset is
      obtained. CONCLUSION: A cost-minimization strategy for bariatric surgery in
      Sweden should not expand indication, but rather increase the number of surgeries
      within the currently accepted indication.

PMID- 22968244
TI  - Obesity has a negative impact on clinical outcome after total knee arthroplasty.
AB  - BACKGROUND AND AIMS: Obesity has been linked to the development of osteoarthritis
      of the knee and since the incidence of obesity is increasing, the need for total
      knee arthroplasty (TKA) is likely to increase. Conflicting findings have been
      reported concerning the relationship between obesity and TKA. It has been shown
      in several studies, that obese patients have poorer clinical results after
      operation. On the other hand it has also been reported similar results for obese
      and non-obese patients. The purpose of this study was to analyze clinically and
      radiologically the results of total knee artrhoplasty in obese patients. MATERIAL
      AND METHODS: The study consisted of 48 patients who had a TKA. The patients were
      divided in two groups according their body mass index. Patients of BMI over 30
      were regarded as obese. RESULTS: The obese patients had poorer clinical success
      at the final follow-up, their WOMAC scores were significantly higher compared to
      non-obese (pain 20.7 vs. 11.6; p = 0.021, stiffness 26.9 vs. 13.4; p = 0.006,
      physical function 26.5 vs. 14.4; p = 0.003). Differences were also found in the
      Knee (KS) and Function (FS) scores and a long-term postoperative ROM and (KS:
      83.6 vs. 88.9; p = 0.01, FS: 63.6/76.3; p = 0.051, ROM: 104.6 vs. 109.6; p =
      0.016). Non-obese patients reached better percentage improvement in the KSS
      compared to obese patients (KS change + 194.5% vs. + 59.5%, p = 0.03; FS change +
      51.5% vs. + 14.9%, p = 0.19). CONCLUSIONS: Obesity has a negative impact on the
      outcome of TKA, assessed by patients' clinical function and satisfaction level.

PMID- 22968245
TI  - Increased energy intake in hip fracture patients affects nutritional biochemical
      markers.
AB  - BACKGROUND AND AIMS: We have previously shown that nutritional guidelines
      decreased the incidence of pressure ulcers in hip fracture patients. In the
      present study, we evaluate whether the nutritional biochemical markers S-IGF-1
      (Insulin-like Growth Factor 1), S-Transthyretin and S-Albumin are affected by
      patients' energy intake, and whether the markers are useful as predictors of
      postoperative complications. MATERIAL AND METHODS: Quasi-experimental design,
      with one intervention and one control group, as well as pre- and post-study
      measurements. Eighty-eight hip fracture patients were included: 42 in the control
      group and 46 in the intervention group. The control group received regular
      nutritional support pre- and postoperatively, while the intervention group
      received nutritional support that followed new, improved clinical guidelines from
      admission to five days postoperatively. S-Albumin, S-Transthyretin, C-Reactive
      Protein (S-CRP) and S-IGF-1 were analysed at admission and five days
      postoperatively as well as complications like pressure ulcer and infection.
      RESULTS: The intervention group had a significantly higher energy intake; for
      example, 1636 kcal versus 852 kcal postoperative day 1. S-IGF-1 levels decreased
      significantly in the control group, while no decrease in the intervention group.
      S-Albumin and S-Transthyretin decreased and S-CRP increased significantly in both
      groups, indicating that those markers were not affected short-term by a high
      energy intake. There was no correlation between short-term post-operative
      complications and S-IGF-1, S-Transthyretin or S-Albumin at admission. CONCLUSION:
      The results of our study showed that S-IGF-1 can be used as a short-term
      nutritional biochemical marker, as it was affected by a five-day high-energy
      regimen. However, neither S-IGF-1, S-Transthyretin or S-Albumin were useful in
      predicting postoperative complications within five days postoperatively.

PMID- 22968246
TI  - Femoral neck bone mineral density after resurfacing hip arthroplasty.
AB  - INTRODUCTION: Resurfacing hip arthroplasty (RHA) has been suggested to provide an
      alternative to conventional total hip arthroplasty in younger, active patients.
      It seems to have an ability to conserve the bone mass on the femoral side. Some
      controversy exists regarding to the possible disadvantages of RHA and some of
      them are connected to poor femoral bone quality after surgery. Hence we wanted to
      study the bone mineral density changes 3 and 12 months after RHA. MATERIALS AND
      METHODS: A total of 26 patients (22 men and 4 women, 28 hips) underwent a hip
      resurfacing arthroplasty. The mean age of the patients was 55,2 (range 38-69)
      years. Bone mineral density (BMD) of the proximal femur was measured by using the
      dual-energy X-ray absorptiometry (DXA) postoperatively and within 3 and 12 months
      from surgery. For analysis, we divided the femoral neck area into four equal
      sized regions of interest ranging from the prosthesis to the trochanter level.
      RESULTS: At three months follow-up the BMD changes varied between -5.1% (ROI C)
      and + 1.9% (ROI A), as compared with the immediate postoperative values. After
      one year follow-up the BMD changes were + 1.1% in the ROI A, + 5.4% in the ROI B,
      -3.9% in the ROI C and + 1.3% in the ROI D. The changes in BMD were not
      statistically significant. DISCUSSION: While there is still much debate and room
      for additional research in this topic, the results suggest that BMD is conserved
      in the femoral neck one year after hip resurfacing arthroplasty.

PMID- 22968247
TI  - A critical analysis of postoperative complications of antebrachium TEN-nailing in
      35 children.
AB  - BACKGROUND: Unstable antebrachium diaphyseal fractures in children are nowadays
      increasingly treated operatively by elastic intramedullary nailing. AIM: Aim of
      the study was to critically assess both radiological and functional outcome of
      antebrachium fractures treated by titanium elastic nail (TEN) in a pediatric
      cohort. MATERIAL AND METHODS: This retrospective study investigated 75
      consecutive children, who were treated for antebrachium shaft fractures at
      Tampere University Hospital during the time period from January 2001 to December
      2005. All the fractures were classified according to OTA. Thirty-five children
      (mean age 12.3 years) were treated by TEN-nailing. Twenty four of the forearm
      fractures were instable, five were open, five were re-fractures and one had ulnar
      nerve deficit. In all but one patient both forearm bones were fractured. Twelve
      (34%) operations were managed by closed reduction, open reduction was needed in
      23 (66%) patients. In 29 cases both bones were fixed with TEN-nail. In the four
      patients with re-fracture in both ulna and radius only the radius was TEN-nailed.
      In one case radius was fixed with TEN-nail and ulna with K-wire and in another
      case radius was fixed with TEN-nail and ulna with plate. Fracture pattern, mode
      of reduction, surgical approach, short- and long-term complications and outcome
      were recorded. RESULTS: Twenty three (66%) patients achieved healing of the
      fractures without any limitation in range of motion. Twelve patients with
      postoperative complication were followed up 31-74 (median of 54) months. Eleven
      (31%) patients had minor postoperative complications and one (0,3%) patient had a
      Volkmann's ischemic contracture. Five of complicated patients had more than one
      problem. Immediate post-operative problems were noted in these five patients. At
      follow-up visits four patients complained of ulnar nail discomfort, two had
      neural symptoms. Additionally, three children suffered from re-fractures.
      DISCUSSION: Despite various minor complications, TEN-nailing is considered
      suitable treatment for unstable forearm shaft fractures. Most of the problems
      were related to poor technical performance in nailing.

PMID- 22968248
TI  - Successful femoral reconstruction with a fluted and tapered modular distal
      fixation stem in revision total hip arthroplasty.
AB  - BACKGROUND AND AIMS: Early results of fluted and tapered distal fixation stems
      used in reconstruction of deficient femora in femoral revision arthroplasty have
      been successful in small series. We evaluated the survival of the LINK MP
      Reconstruction Hip Stem and factors associated with survival using data from a
      nation-wide arthroplasty register. MATERIALS AND METHODS: 408 femoral revisions
      using LINK MP Reconstruction Hip Stem were performed during 1994 to 2007. The
      mean age of the patients was 72.5 (range: 36-93) years and 63% were performed in
      women. Kaplan-Meier analysis and the Cox regression model were used for the
      survival analysis. The effects of age, sex and diagnoses were also studied.
      RESULTS: The 9-year overall survivorship for the LINK MP Reconstruction Hip Stem
      was 75% (95% CI 70-80). Aseptic loosening was rare; the 9-year revision rate for
      aseptic loosening was only 3%, which coincides with earlier reports with shorter
      folllow-up. The most common reason for re-revision was dislocation of the
      prosthesis with or without malposition of the socket (67%). Indication for
      revision strongly affected the survival rate with revisions for dislocation
      having an over 3-fold and revisions for infection a 3-fold relative risk for re
      revision compared to revisions for aseptic loosening. Increasing age slightly
      decreased the risk of re-revision but sex did not affect the survival.
      DISCUSSION: Based on our findings, we conclude LINK MP Reconstruction Hip Stem,
      as an example of a fluted and tapered distal fixation stem, appears to solve many
      problems with implant fixation in femoral revisions. High number of dislocations
      suggests that special attention should be paid to correct center of rotation, to
      correct implant positioning and to need of constrained implants in case of
      deficient abductor mechanism.

PMID- 22968249
TI  - Development and evaluation of theory-based diabetes support services.
AB  - Technology-enabled support services for diabetes can fulfill patient demand to
      care for diabetes independently. Patients benefit from such services after
      greater adoption of the services in healthcare systems. Unfortunately,
      conventional service development fails to thoroughly understand patient care
      support, making it difficult to achieve the desired design, and posing
      substantial challenges in adopting these services. Thus, previously developed
      services in many cases are not as patients expected, as evidenced by their low
      acceptance among patients. To solve this problem, adequate strategies must be
      developed by incorporating theoretical knowledge as a solid foundation in order
      to improve service design. This study develops technology-enabled diabetes
      support services based on the self-care theory. A set of self-care service
      scenarios is also established and combined with theoretical concepts. The
      developed services consist of a nurse-led consultation service and a mobile
      application service. Additionally, user acceptance is confirmed by assessing
      patient perceptions of the diabetes support services in a group of patients with
      diabetes (N=27). Results of analysis reveal that patients respond favorably
      toward the services. Patient preference and perceived ease of use attest to their
      intention to use the services. Greater adoption of the services can be
      anticipated, owing to a higher levels of preference and higher perceived ease of
      use. This study demonstrated that the self-care theory can be linked to nursing
      informatics research and chronic care clinical practices.

PMID- 22968250
TI  - Successful teriparatide treatment of atypical fracture after long-term use of
      alendronate without surgical procedure in a postmenopausal woman:  a case report.
AB  - OBJECTIVE: Bisphosphonates are used as first-line therapy for postmenopausal
      osteoporosis owing to their potent inhibition of bone resorption. Long-term use
      of bisphosphonates may lead to low-energy femoral subtrochanteric or shaft
      fractures in a very few patients. The aim of this study was to describe the
      clinical course of a patient treated with alendronate for 3 years who developed
      an atypical femoral fracture and to hypothesize the beneficial effects of
      teriparatide on the healing of the patient's atypical femoral fracture. METHODS:
      A 63-year-old Asian woman had a lumbar osteoporotic fracture and received 70 mg
      of alendronate for 3 years. Pain and soreness in the thigh presented initially
      and exacerbated thereafter. X-ray revealed a right femoral diaphysis stress
      fracture. She then received teriparatide for the treatment of osteoporosis and
      the femoral atypical fracture. RESULTS: Pain and tenderness improved remarkably
      after teriparatide treatment for 1 month, and these symptoms disappeared after
      teriparatide treatment for 9 months. The patient also received raloxifen as
      further therapy, and the fracture line had completely disappeared by 15 months
      after treatment. CONCLUSIONS: Even though a previous study has reported that
      teriparatide healed stress fractures in a rat model and even with the time course
      of fracture healing in our patient, we are still not certain that teriparatide
      played a primary role in the positive response to therapy. Vitamin D therapy,
      calcium, and alendronate discontinuation may have played secondary roles. This
      case report may serve to introduce a direction for future research into the
      pharmacological treatment of atypical femoral fractures. Surgical treatment of
      incomplete atypical femoral fractures may be a safer method.

PMID- 22968251
TI  - Role of antimullerian hormone as a biomarker of the menopausal transition.
AB  - OBJECTIVE: The objectives of this study were to clarify changes in antimullerian
      hormone (AMH) concentrations during the menopausal transition and to determine
      whether AMH may serve as a marker to predict the onset of menopause. METHODS:
      Blood samples were collected annually for 6 years from 595 women living in Iwaki,
      Japan. We selected 44 women according to strict criteria: those older than 40
      years at first participation; those who had their regular menstruation; those
      whose menstrual cycle had changed from regular to irregular or those who met the
      final menstrual period; and those who did not take medication that may affect the
      menstrual cycle. Serum AMH concentrations were determined by the newly developed
      AMH Gen II assay kit. Stage of the menopausal transition was defined according to
      the Stages of Reproductive Aging Workshop. RESULTS: Among the 44 women who
      participated in the study, 29 experienced menopause during the study (group A),
      whereas the remainder developed irregular menstrual cycles (group B). AMH was
      consistently found to be undetectable for 3 years before menopause, suggesting
      that AMH is a sensitive marker for predicting the onset of menopause. In
      addition, serum AMH was detectable at low levels in women from group B until
      menstrual cycles became irregular, suggesting that AMH serves as a marker for
      diagnosing the menopausal transition. CONCLUSIONS: When AMH levels fall below
      detectable levels, women at the menopausal transition will progress to menopause
      within 3 years.

PMID- 22968252
TI  - Impact of energy restriction with or without resistance training on energy
      metabolism in overweight and obese postmenopausal women:  a Montreal Ottawa New
      Emerging Team group study.
AB  - OBJECTIVE: The present study measured the impact of adding resistance training to
      an energy-restricted diet on the components of energy expenditure in overweight
      or obese postmenopausal women. METHODS: Participants (n = 137) were randomly
      divided into two groups: (1) a diet and resistance training (DRT) group and (2) a
      diet-only (DO) group. Women followed a 6-month energy-restricted diet consisting
      of 2,100 to 3,360 kJ less than daily needs. The DRT group also followed a
      resistance training program (three times a week). Resting energy expenditure
      (REE) was measured by indirect calorimetry. Total energy expenditure was measured
      with doubly labeled water. Body composition was measured by dual-energy x-ray
      absorptiometry. RESULTS: Eighty nine women were included in the analyses for this
      study (DRT, n = 21; DO, n = 68). REE in both groups was significantly lower after
      the intervention (mean difference +/- SD: DO, -0.26 +/- 0.4 MJ d; DRT, -0.33 +/-
      0.4 MJ d; P <= 0.05). Relative REE, expressed per kilogram of lean body mass
      corrected for fat mass change, remained stable in both groups. Physical activity
      energy expenditure remained stable in both groups (mean difference +/- SD: DO,
      0.02 +/- 1 MJ d, P = 0.91; DRT, -0.14 +/- 1 MJ d, P = 0.64). CONCLUSIONS: Adding
      resistance training to an energy-restricted diet does not significantly alter any
      compartment of energy expenditure. REE is lower owing to reduction in body
      composition compartments, but relative REE is not significantly altered.

PMID- 22968253
TI  - Relationship of body mass index and body fat distribution with postural balance
      and risk of falls in Spanish postmenopausal women.
AB  - OBJECTIVE: Menopause status has been associated with weight gain and increased
      central adiposity. Obesity and postural instability are related to an increased
      risk of falls. The purpose of our study was to analyze the association of body
      weight and body fat distribution with postural balance and their correlation with
      falls in postmenopausal women. METHODS: A cross-sectional, observational study
      was conducted on 100 postmenopausal women aged 50 to 65 years with at least 12
      months of amenorrhea. The participants were divided into obese, overweight, and
      normal-weight groups according to their body mass index (BMI) and into android,
      uniform, and gynoid body fat distribution types according to waist-to-hip ratio.
      Postural stability was assessed with force platforms. chi and Kruskal-Wallis
      tests were used for statistical analysis. RESULTS: A total of 18 participants
      reported falls in the previous 12 months. The obese group had significantly
      higher values for the root-mean-square amplitude of the center of pressure in the
      posteroanterior direction under both eyes-open and eyes-closed conditions (P =
      0.005 and P = 0.007, respectively), as well as for the velocity of center-of
      pressure displacements (P = 0.032). In the android group, most stabilometric
      parameters under the condition "eyes open and standing on a foam surface" were
      significantly higher, whereas greater values were observed in the uniform-type
      group with eyes closed. A BMI of 25 kg/m or higher (odds ratio, 3.58; 95% CI,
      1.07-11.9; P = 0.038) and android body fat distribution (odds ratio, 5.35; 95%
      CI, 1.75-16.39; P = 0.003) were correlated with the risk of falling. CONCLUSIONS:
      Postural instability is associated with obesity and uniform and android body fat
      distribution types (waist-to-hip ratio > 0.76) in Spanish postmenopausal women
      aged 50 to 65 years. Our results also suggest that a BMI of 25 kg/m or higher and
      android body fat distribution can be considered as independent risk factors for
      falls.

PMID- 22968254
TI  - Baseline hysteroscopic assessment of endometrium in asymptomatic postmenopausal
      women with estrogen receptor-positive breast cancer.
AB  - OBJECTIVE: The goal of this study was to evaluate the true prevalence of
      endometrial pathology in asymptomatic postmenopausal estrogen receptor-positive
      (ER-positive) breast cancer patients and to know whether some patients are
      particularly at risk. METHODS: A preliminary cross-sectional study was carried
      out with 130 postmenopausal ER-positive breast cancer patients. Before any
      treatment, diagnostic hysteroscopy and endometrial biopsy were performed in all
      women. Histopathological findings were considered the gold standard in estimating
      the prevalence of endometrial disease, which was analyzed according to different
      risk factors. RESULTS: Hysteroscopic evaluation was possible in 118 patients
      (90.7%). Of these patients, 68.6% were older than 60 years, and 51.4% were obese.
      Endometrial polyps were found in 35 patients (29.6%; 1 polyp with simple
      hyperplasia), and simple endometrial hyperplasia was found in 1 patient (0.8%),
      with an overall morbidity of the endometrium of 31.3%. Among all the well
      established individual risk factors for endometrial pathology, only patient age,
      body mass index, and time since menopause were significant predictors of
      endometrial pathology and/or polyps. There was no statistical difference in the
      thicknesses of the endometrial lining, but many patients with an endometrial
      lining of less than 4 mm had polyps of less than 5 mm. CONCLUSIONS: Asymptomatic
      postmenopausal women with ER-positive breast cancer have a very high prevalence
      of baseline subclinical endometrial abnormalities. Therefore, endometrial
      screening before tamoxifen treatment may be useful in all of these patients, and
      we believe that it should be performed by hysteroscopy in patients at high risk
      (obese and older women).

PMID- 22968255
TI  - Platelet reactivity and thrombogenicity in postmenopausal women.
AB  - OBJECTIVE: Age-adjusted incidence of cardiovascular disease, including myocardial
      infarction, is significantly lower in premenopausal women than in men, which is
      thought to be caused by the cardioprotective effects of estrogen. However, there
      is a consistent increase in the incidence of coronary artery disease in
      postmenopausal women in comparison with premenopausal women. The protective
      benefit of hormone therapy has not been observed in postmenopausal women. It is
      unknown whether measures of platelet reactivity and clot strength contribute to
      the disproportionate incidence of cardiovascular disease between premenopausal
      and postmenopausal women. METHODS: Fifty healthy volunteers, including 25
      premenopausal women and 25 postmenopausal women, aged between 40 and 65 years
      were enrolled. Total estradiol and follicle-stimulating hormone levels were
      measured for confirmation of menopausal state and comparison testing. Platelet
      reactivity was assessed using light transmission aggregometry and P-selectin, and
      glycoprotein IIb/IIIa receptor expression was assessed using flow cytometry.
      Thrombelastography was used to measure clot strength, clotting time, and
      fibrinogen activity. Serum cholesterol, C-reactive protein, complete blood count,
      and comprehensive metabolic panel were also measured. RESULTS: Platelet
      reactivity did not differ among menopausal states or hormone levels. Clotting
      time was increased in postmenopausal women (6.6 +/- 2.0 vs. 7.8 +/- 1.2 min, P =
      0.013) and significantly correlated with estradiol levels (r = 0.68, P < 0.001).
      A significantly higher low-density lipoprotein cholesterol level was observed in
      postmenopausal women (P = 0.05). Mean C-reactive protein levels were numerically
      higher in the postmenopausal group. CONCLUSIONS: The thrombotic risk profile
      between premenopausal and postmenopausal women is similar. However, improved
      management of cholesterol may be of clinical benefit. Large-scale studies are
      required to validate these findings.

PMID- 22968256
TI  - Effect of low-dose alendronate treatment on bone mineral density and bone
      turnover markers in Chinese postmenopausal women with osteopenia and
      osteoporosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of low-dose
      alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover
      markers in Chinese postmenopausal women with osteopenia and osteoporosis.
      METHODS: This study was a large-sample, randomized, open-label, prospective,
      multicenter, clinical trial with a 12-month follow-up. A total of 639
      postmenopausal women (aged 62.2 +/- 7.0 y) with osteopenia or osteoporosis were
      randomized into two groups: low-dose ALN (70 mg every two weeks) and standard
      dose ALN (70 mg weekly). All patients were also supplemented with calcium (600
      mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray
      absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers
      (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation
      marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12
      months of treatment. BMD and bone turnover markers were compared between the
      baseline and the end of treatment, and the changes in BMD and bone turnover
      markers were also compared between the low-dose ALN group and the standard-dose
      ALN group. RESULTS: No significant differences in age, years since menopause,
      body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers
      were found at baseline between the two dose groups. A total of 558 (87.3%) and
      540 (84.5%) women completed the treatment at the 6th and 12th months,
      respectively. After the 12-month treatment, lumbar spine and hip BMD increased
      and serum bone turnover markers decreased significantly in both of the treatment
      groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar
      spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%,
      and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%,
      respectively; P > 0.05). However, levels of serum alkaline phosphatase and
      carboxy-telopeptide of type I collagen in the standard-dose group decreased
      moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The
      women tolerated the two doses of ALN quite well. Adverse effects were similar in
      the two groups. CONCLUSIONS: Treatment with low-dose ALN (70 mg every two weeks)
      in women with postmenopausal osteopenia or osteoporosis effectively increases
      lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose
      ALN may be a cost-effective and safe protocol for treating osteopenia or
      osteoporosis in Chinese women.

PMID- 22968257
TI  - Is there a link between premature ovarian failure and serum concentrations of
      vitamin D, zinc, and copper?
AB  - OBJECTIVE: The risk of primary ovarian insufficiency (POI) increases in
      association with autoimmune conditions. Adequate intake of vitamin D (vit D) and
      trace elements is required for the immune system to function efficiently. The aim
      of this study was to evaluate vit D, zinc, and copper blood levels in women with
      POI who had given birth to at least one child and in women with normal menstrual
      cycles. METHODS: This was a cross-sectional, case-control study involving 63
      participants divided into two groups: the study group, which is composed of 35
      women with POI, and the control group, which is composed of 28 women with normal
      menstrual cycles. Serum concentrations of zinc, vit D, and copper were determined
      for each participant. RESULTS: Women with POI had significantly higher serum
      copper levels and copper-to-zinc ratio but significantly lower serum vit D and
      zinc levels when compared with the healthy control group. Serum follicle
      stimulating hormone levels were inversely correlated with zinc and vit D levels
      and positively correlated with the copper-to-zinc ratio and copper levels. Vit D
      levels were inversely correlated with follicle-stimulating hormone levels, copper
      to-zinc ratio, and copper levels and positively correlated with zinc levels.
      CONCLUSIONS: Most women with POI are deficient in vit D. Zinc, copper, and vit D
      seem to correlate with hormonal status in the participants. The present study may
      generate hypotheses for future studies that will investigate the possible
      mechanisms behind alterations in trace elements and vit D deficiency in women
      with POI and whether these changes could be used to screen for the risk of
      developing POI.

PMID- 22968259
TI  - Facile synthesis of electrophilic vinyl boranes: reactions of alkynyl-borates and
      diazonium salts.
AB  - Reactions of alkynylborate salts, easily derived from reaction of frustrated
      Lewis pairs with terminal alkynes, with diazonium salts to induce 1,1
      carboboration affording a facile and efficient route to substituted electrophilic
      vinyl boranes.

PMID- 22968260
TI  - Migration and chemical reaction of H+ in protonated beta-galactose.
AB  - Equilibrium structures for a proton on beta-D-galactose and transition states for
      proton hopping are computed. Also, Ab Initio Molecular Dynamics (AIMD)
      simulations are carried out. All calculations used B3LYP potentials with
      dispersion. At 40 K, proton hopping between sites is of near microsecond
      timescale. At 300 K, the proton migrates across the sugar on a sub-picosecond
      timescale. At 500 K, the proton reacts with the sugar to produce H(2)O.
      Implications for sugar chemistry are discussed.

PMID- 22968263
TI  - Laser differential confocal radius measurement system.
AB  - A laser differential confocal radius measurement system with high measurement
      accuracy is developed for optical manufacturing and metrology. The system uses
      the zero-crossing point of the differential confocal intensity curve to precisely
      identify the cat's-eye and confocal positions and uses an interferometer to
      measure the distance between these two positions, thereby achieving a high
      precision measurement for the radius of curvature. The coaxial measuring optical
      path reduces the Abbe error, and the air-bearing slider reduces the motion error.
      The error analysis indicates the theoretical accuracy of the system is up to 2
      ppm, and the experiment shows that the system has high focusing sensitivity and
      is little affected by environmental fluctuations; the measuring repeatability is
      between 4 and 12 ppm.

PMID- 22968264
TI  - Distributed liquid level sensors using self-heated optical fibers for cryogenic
      liquid management.
AB  - We present a continuous liquid level sensing system for both room temperature and
      cryogenic fluids with millimeter spatial resolution. Change of in-fiber Rayleigh
      backscattering signal from the distinct thermal response of the heated sensing
      fiber in liquid and in air were interrogated and spatially resolved using the
      optical frequency domain reflectometry. Both electrical and optical heating
      techniques were investigated for cryogenic liquid applications at 4 K, 77 K, and
      the room temperature. The successful combination of self-heated fiber and
      wavelength-swept Rayleigh scattering interferometry provides, for the first time
      to our best knowledge, a truly distributed fuel gauge with high spatial
      resolution for cryogenic fuel storage, transportation, and management on ground
      and in space.

PMID- 22968265
TI  - Theoretical considerations for anticipating of function analysis on a gradient
      index-lens fabrication through double ion-exchange process.
AB  - Based on precise and detailed theoretical examination of diffusion equation
      analysis, two-step Ag(+)-Na(+) and Na(+)-Ag(+) ion-exchange parameters were
      optimized in order to fabricate a gradient index (GRIN) lens in the BK7 glass
      rod. Using the diffusion equation, the impact of the concentration ratio of the
      exchanged ion during the first and second steps was examined in detail. Then,
      based on the calculated effective parameters such as concentration ratio and
      immersion time, a fabrication process was proposed. We managed to get the optimum
      parameters (the bath stop time, temperature, and length) to make a quarter pitch
      lens. As a result, some samples of the GRIN lens were fabricated and tested
      successfully. Theoretical considerations and experimental results are presented.

PMID- 22968266
TI  - Slow-light element for tunable time delay based on optical microcoil resonator.
AB  - We propose a simple and compact slow-light element by use of an optical microcoil
      resonator (OMR) constituted by two microfiber coils. Based on the matrix
      exponential method, we solve the coupled-wave equations of the OMR with n turns
      of microfiber coils and obtain a general solution. Simulations indicate that a
      tunable slow-light propagation can be obtained by controlling the coupling
      coefficient between the two adjacent microfiber coils by means of regulating the
      voltage applied to the ferroelectric crystal. A slow-light time delay up to 62 ps
      with a bandwidth of 0.4 nm is performed at the wavelength around 1.5 MUm.

PMID- 22968267
TI  - Coherent backscattering cone shape depends on the beam size.
AB  - Coherent backscattering (CBS) is a beautiful physical phenomenon that takes place
      in a highly scattering medium, which has potential application in noninvasive
      optical property measurement. The current model that explains the CBS cone shape,
      however, assumes the incoming beam diameter is infinitely large compared to the
      transport length. In this paper, we evaluate the effect of a finite scalar light
      illumination area on the CBS cone, both theoretically and experimentally. The
      quantitative relationship between laser beam size and the CBS cone shape is
      established by using two different finite beam models (uniform top hat and
      Gaussian distribution). A series of experimental data with varying beam diameters
      is obtained for comparison with the theory. Our study shows the CBS cone shape
      begins to show distortion when beam size becomes submillimeter, and this effect
      should not be ignored in general. In biological tissue where a normal large beam
      CBS cone is too narrow for detection, this small beam CBS may be more
      advantageous for more accurate and higher resolution tissue characterization.

PMID- 22968268
TI  - Intensity invariant complex encoded color correlation.
AB  - Optical correlation has traditionally processed monochromatic gray-scale images.
      This paper develops a new encoding mechanism that uses the chromaticity of the
      input signal. It is then not only possible to detect different colored objects,
      but the system is also invariant to changes in the brightness of the lighting,
      including variations across the object.

PMID- 22968269
TI  - Super-resolving random-Gaussian apodized photon sieve.
AB  - A novel apodized photon sieve is presented in which random dense Gaussian
      distribution is implemented to modulate the pinhole density in each zone. The
      random distribution in dense Gaussian distribution causes intrazone
      discontinuities. Also, the dense Gaussian distribution generates a substantial
      number of pinholes in order to form a large degree of overlap between the holes
      in a few innermost zones of the photon sieve; thereby, clear zones are formed.
      The role of the discontinuities on the focusing properties of the photon sieve is
      examined as well. Analysis shows that secondary maxima have evidently been
      suppressed, transmission has increased enormously, and the central maxima width
      is approximately unchanged in comparison to the dense Gaussian distribution.
      Theoretical results have been completely verified by experiment.

PMID- 22968270
TI  - Correction of error motion in a line-scanning tomographic optical microscope.
AB  - A line-scanning tomographic optical microscope system requires precise rotation
      of the scanning line. Center of rotation error introduced by both the imprecision
      of optical and mechanical components is studied experimentally and via
      simulations. It was shown that a practical tolerance limit can be chosen where
      the influence of the investigated error on the reconstructed image quality
      remains insignificant. An effective and simply practical solution was presented
      to keep the center of rotation error below this tolerance limit and the spatial
      resolution of the reconstructed image close to the diffraction limit.

PMID- 22968271
TI  - Propagation of polarized light through textile material.
AB  - In this paper a detailed investigation, based on simulations and experiments of
      polarized light propagation through textile material, is presented. The fibers in
      textile material are generally anisotropic with axisymmetric structure. The
      formalism of anisotropic fiber scattering (AFS) at oblique incidence is first
      deduced and then, based on this formalism and considered multiscattering, a
      polarization-dependent Monte Carlo method is employed to simulate the propagation
      of polarized light in textile material. Taking cotton fiber assemblies as
      samples, the forward-scattering Mueller matrices are calculated theoretically
      through the AFS-based simulations and measured experimentally by an improved
      Mueller matrix polarimeter. Their variations according to sample thickness are
      discussed primarily. With these matrices polar-decomposed, a further discussion
      on the optical polarization properties of cotton fiber assemblies (i.e.,
      depolarization Delta, diattenuation D, optical rotation psi and linear retardance
      delta) versus the thickness is held. Simultaneously, a meaningful comparison of
      both the matrices and their polar decomposition, generated from the simulations
      based on isotropic fiber scattering (IFS), with those simulated based on AFS is
      made. Results show that the IFS-derived values are strikingly different from
      those that are AFS-derived due to ignoring the fiber anisotropy. Furthermore, all
      the AFS-derived results are perfectly consistent with those obtained
      experimentally, which suggests that the Monte Carlo simulation based on AFS has
      potential applications for light scattering and propagation in textile material.

PMID- 22968272
TI  - Optimized compressive sampling for passive millimeter-wave imaging.
AB  - In this paper, we briefly describe a single detector passive millimeter-wave
      imaging system, which has been previously presented. The system uses a cyclic
      sensing matrix to acquire incoherent measurements of the observed scene and then
      reconstructs the image using a Bayesian approach. The cyclic nature of the
      sensing matrix allows for the design of a single unified and compact mask that
      provides all the required random masks in a convenient way, such that no
      mechanical mask exchange is needed. Based on this setup, we primarily propose the
      optimal adaptive selection of sampling submasks out of the full cyclic mask to
      obtain improved reconstruction results. The reconstructed images show the
      feasibility of the imaging system as well as its improved performance through the
      proposed sampling scheme.

PMID- 22968273
TI  - Modeling of fiber-optic fluorescence probes for strongly absorbing samples.
AB  - The dynamic range of fiber-optic fluorescent probes such as single fibers and
      fiber bundles is calculated for strongly absorbing samples, such as process
      liquids, foodstuffs, and lubricants. The model assumes an excitation beam profile
      based on a Lambertian light source and uses analytical forms of the collection
      efficiency, followed by an Abel transformation and numerical integration. It is
      found that the effect of primary absorption of the excitation light and secondary
      absorption of the fluorescence is profound. For fiber bundles and bifurcated
      fiber probes, the upper accessible concentration limit is roughly given by the
      absorption length of the primary and secondary absorption. Fluorescence detectors
      that are placed at right angles to the excitation beam axis or collinear to the
      beam axis are equally strongly affected by secondary absorption. A probe in which
      the same fiber is used for excitation and for collection of the fluorescence
      emerges as the fiber probe with the largest accessible concentration range.

PMID- 22968274
TI  - Generation of microstripe cylindrical and toroidal mirrors by localized laser
      evaporation of fused silica.
AB  - We report a new technique for the rapid fabrication of microstripe cylindrical
      and toroidal mirrors with a high ratio (>10) of the two principal radii of
      curvature (RoC(1)/RoC(2)), and demonstrate their effectiveness as mode-selecting
      resonator mirrors for high-power planar waveguide lasers. In this process, the
      larger radius of curvature (RoC(1)) is determined by the planar or cylindrical
      shape of the fused silica substrate selected for laser processing, whilst the
      other (RoC(2)) is produced by controlled CO(2) laser-induced vaporization of the
      glass. The narrow stripe mirror aperture is achieved by applying a set of
      partially overlapped laser scans, with the incident laser power, the number of
      laser scans, and their spacing being used to control the curvature produced by
      laser evaporation. In this work, a 1 mm diameter laser spot is used to produce
      grooves of cylindrical/toroidal shape with 240 MUm width and 16 mm length. After
      high reflectance coating, these grooves are found to provide excellent mode
      selectivity as resonator mirrors for a 150 MUm core Yb:YAG planar waveguide
      laser, producing high brightness output at more than 300 W. The results show
      clearly that the laser-generated microstripe mirrors can improve the optical
      performance of high-power planar waveguide lasers when applied in a low-loss mode
      selective resonator configuration.

PMID- 22968275
TI  - Temperature sensor based on surface plasmon resonance within selectively coated
      photonic crystal fiber.
AB  - We demonstrate a temperature sensor based on surface plasmon resonances supported
      by photonic crystal fibers (PCFs). Within the PCF, to enhance the sensitivity of
      the sensor, the air holes of the second layer are filled with a large thermo
      optic coefficient liquid and some of those air holes are selectively coated with
      metal. Temperature variations will induce changes of coupling efficiencies
      between the fundamental core mode and the plasmonic mode, thus leading to
      different loss spectra that will be recorded. In this paper, variations of the
      dielectric constants of all components, including the metal, the filled liquid,
      and the fused silica, are considered. We conduct numerical calculations to
      analyze the mode profile and evaluate the power loss, demonstrating a temperature
      sensitivity as high as 720 pm/ degrees C.

PMID- 22968276
TI  - Programmable color tuning of a multiline laser by means of a twisted nematic
      liquid crystal display.
AB  - An optical system useful to tune in a controlled way the color of a triline argon
      krypton (Ar-Kr) laser by means of a twisted nematic liquid crystal display
      (TNLCD) is presented. The optical setup employs a 4f system and two blazed
      gratings to first separate and then recombine the spectrum of the light beam. The
      TNLCD is included in the intermediate focal plane operating in the amplitude
      modulation mode to control the relative transmission of each spectral line. The
      resulting color is accurately predicted by using a previously developed physical
      model of the spectral and voltage dependence of the TNLCD birefringence. By
      simply changing the gray level image addressed to the display, the Ar-Kr laser is
      color modulated at a video rate, thus becoming an interesting, reconfigurable,
      coherent light source for applications such as multicolor holography or color
      inspection.

PMID- 22968277
TI  - Energy transportation in a subwavelength waveguide composed of a pair of comb
      shape nanorod chains.
AB  - A subwavelength plasmonic waveguide composed of a pair of comb-shape nanorod
      chains is proposed. The electromagnetic energy can be transported in the
      waveguide via the interaction strength of magnetoinductive coupling as well as
      conduction current exchange. Finite Element Method simulation results reveal that
      for such a waveguide composed of 50 pairs of 400 nm-long-nanorods, a passband
      ranging from zero to cutoff frequency 156.2 THz, and an effective propagation
      length of 20.87 MUm can be achieved simultaneously. The proposed mechanism of
      energy transport in the nanoscale has potential applications in subwavelength
      transmission lines for a wide range of integrated optical devices.

PMID- 22968278
TI  - Design of ultrahigh brightness solar-pumped disk laser.
AB  - To significantly improve the solar-pumped laser beam brightness, a multi-Fresnel
      lens scheme is proposed for side-pumping either a single-crystal Nd:YAG or a core
      doped ceramic Sm(3+) Nd:YAG disk. Optimum laser system parameters are found
      through ZEMAX and LASCAD numerical analysis. An ultrahigh laser beam figure of
      merit B of 53 W is numerically calculated, corresponding to a significant
      enhancement of more than 180 times over the previous record. 17.7 W/m(2)
      collection efficiency is also numerically attained. The strong thermal effects
      that have hampered present-day rod-type solar-pumped lasers can also be largely
      alleviated.

PMID- 22968279
TI  - A way to super resolution by a sampling method using the spectral properties of
      one-dimensional multilayer systems.
AB  - A way to perform sampling of the evanescent spectrum of an object is considered
      by using a photonic bandgap (PBG). The coupling between the scattered field from
      the object and the PBG is discussed, showing a connection of the guide modes with
      selected spectral components of the scattering object in free space. Some useful
      examples have been discussed, showing good agreement between numerical results
      and theoretical previsions.

PMID- 22968280
TI  - Rotation of nanowires with radially higher-order Laguerre-Gaussian beams produced
      by computer-generated holograms.
AB  - In this paper, the influence of radially higher index p of Laguerre-Gaussian (LG)
      beams on the rotation of nanowires is studied. Radially higher-order LG beams are
      produced by computer-generated holograms, which are displayed on a spatial light
      modulator. A series of experiments on manipulating ZnO nanowires was performed on
      our holographic optical tweezers platform. The experiments demonstrated that
      radially higher-order LG beams could effectively rotate nanowires along the
      innermost bright ring of themselves. Compared with radially low-order LG beams,
      they have larger torques exerted on nanowires and can make nanowires rotate more
      quickly.

PMID- 22968281
TI  - Sub-10-fs deep-ultraviolet light source with stable power and spectrum.
AB  - In some applications of ultrafast spectroscopy that employ sub-10-fs pulses, the
      pulse spectrum and power need to be stable for several tens of minutes. In this
      study, we generate sub-10-fs deep-ultraviolet (DUV) pulses with such stabilities
      by chirped-pulse four-wave mixing. A power fluctuation of less than 3% rms was
      realized by employing stabilization schemes that employ a power stabilizer. The
      pulses generated in this study have been applied to transient absorption
      spectroscopy in the DUV with a sub-10-fs time resolution [Phys. Chem. Chem.
      Phys.14, 6200 (2012).10.1039/c2cp23649d]. This sub-10-fs DUV source has a similar
      performance to widely used noncollinear optical parametric amplifiers.

PMID- 22968282
TI  - Optical model and optimal output coupler for a continuous wave Yb:YAG thin-disk
      laser with multiple-disk configuration.
AB  - This article presents the fundamental principles of operational performance of a
      continuous wave (cw) thin-disk laser with multiple disks in one resonator. Based
      on the model of an end-pumped Yb:YAG thin-disk laser with nonuniform temperature
      distribution, the effect of the multiple disks in one resonator is considered.
      The analytic expressions are derived to analyze the laser output intensity, laser
      intensity in the resonator, threshold intensity, and the optical efficiency of a
      thin-disk laser with multiple disks arranged in series. The dependence of output
      coupler reflectivity and the number of thin disks on various parameters are
      investigated, which are useful to determine the optimal output coupler
      reflectivity of the thin-disk lasers and control the laser intensity in the
      resonator.

PMID- 22968283
TI  - Two-step camera calibration method based on the SPGD algorithm.
AB  - Given the rapid convergence characteristic of the stochastic parallel gradient
      descent (SPGD) algorithm, this study proposes a method that applies the algorithm
      to a two-step camera calibration method to resolve the frequent iteration and
      long calibration time deficiencies that exist under the traditional two-step
      camera calibration method, thereby achieving rapid calibration. The method first
      uses image coordinates obtained with subpixel positioning technology as initial
      values of control variables, in addition to positive disturbances produced on a
      two-dimensional plane, then uses two-step theory to calculate the average value
      of aberrations. Based on the same rationale, negative disturbances are then
      produced and the average value of the aberrations is calculated. Finally if,
      after assessing whether to continue with further iterations based on the
      difference in these values, continued iterations confirm new control variables
      based on the SPGD algorithm iteration formula, a new cycle is started until the
      results satisfy requirements. Theoretical analysis and experimental results show
      that the proposed rapid calibration method using the SPGD algorithm in the two
      step camera calibration method is 3-4 times faster than the traditional two-step
      calibration method, and that it has significant potential value for use in
      certain time-constrained projects.

PMID- 22968284
TI  - Improved collimation testing technique.
AB  - Laser collimation is an essential part of many experimental setups including
      optical coherent processors, image transformers, Fourier transform generators,
      and 4f-based optical systems. A device is required to test the collimation of
      lasers in such experiments. We are proposing a modification in the existing two
      lens-system (TLS)-based collimation testing technique in which a combination of a
      convex and a concave lens is placed in space between the collimating lens and the
      first grating of the conventional setup. In the proposed method, we change the
      position of the second TLS component, placing it between the two gratings. The
      proposed idea not only reduces the size of the system but also gives improved
      results. Theoretical modeling and simulated and experimental results are
      presented to support our idea.

PMID- 22968285
TI  - Jahn-Teller distortions in transition metal compounds, and their importance in
      functional molecular and inorganic materials.
AB  - This tutorial review discusses the structural and electronic consequences of the
      Jahn-Teller effect in transition metal complexes, focussing on copper(ii)
      compounds which tend to be the most studied. The nature of a Jahn-Teller
      distortion in molecular complexes and extended lattices can be manipulated by
      application of pressure or temperature, by doping a molecule into a host lattice,
      or simply by molecular design. Many of these results have been achieved using
      compounds with a trans-[CuX(4)Y(2)] coordination sphere, which seems to afford
      copper centres that are particularly sensitive to their environment. Jahn-Teller
      distortions lead to some unusual phenomena in molecular magnetism, and are
      important to the functionality of important classes of conducting and
      superconducting ceramics.

PMID- 22968286
TI  - Use of animal models of human disease for nonclinical safety assessment of novel
      pharmaceuticals.
AB  - Animal models of human disease are commonly utilized to gain insight into the
      potential efficacy and mode of action of novel pharmaceuticals. However,
      conventional (healthy) rodent and nonrodent models are generally utilized in
      nonclinical safety testing. Animal models of human disease may be helpful in
      understanding safety risks of compounds in nonclinical or clinical development,
      with their greatest value being in targeted or hypothesis-driven studies to help
      understand the mechanism of a particular toxicity. Limitations of animal models
      of disease in nonclinical safety testing include a lack of historical control,
      heterogeneity in disease expression, a limited life span, and confounding effects
      of the disease. In most instances, animal models of human disease should not be
      utilized to supplant testing in conventional animal models. While of potential
      benefit, testing in an animal model of human disease should only be taken after
      adequate consideration of relevance along with benefits and limitations of the
      proposed model.

PMID- 22968287
TI  - Atypical Leydig cell hyperplasia in adult rats with low T and high LH induced by
      prenatal Di(n-butyl) phthalate exposure.
AB  - The present study describes atypical Leydig cell (LC) hyperplasia in 20-week-old
      Sprague-Dawley rats with low testosterone and high luteinizing hormone levels
      after prenatal administration of 100 mg/kg/day di(n-butyl) phthalate on days 12
      to 21 postconception. Light microscopy revealed LC hyperplasia surrounded by
      severely degenerated seminiferous tubules. Aggregated LCs had large ovoid nuclei
      with nucleoli and abundant eosinophilic cytoplasm. Immunohistochemical analysis
      showed expression of proliferating cell nuclear antigen and vimentin in many
      hyperplastic LCs. Electron microscopy revealed atypical nuclei, abundant free
      ribosomes, stripped rough endoplasmic reticulum, intermediate-size filaments,
      elongated cytoplasmic filopodia, atypical tight junctions, and cilia formations,
      but smooth endoplasmic reticulum was scarcely observed.

PMID- 22968288
TI  - Mechanical properties of atomic layer deposition-reinforced nanoparticle thin
      films.
AB  - Nanoparticle thin films (NTFs) exhibit multifunctionality, making them useful for
      numerous advanced applications including energy storage and conversion,
      biosensing and photonics. Poor mechanical reliability and durability of NTFs,
      however, limit their industrial and commercial applications. Atomic layer
      deposition (ALD) represents a unique opportunity to enhance the mechanical
      properties of NTFs at a relatively low temperature without drastically changing
      their original structure and functionality. In this work, we study how ALD of
      different materials, Al(2)O(3), TiO(2), and SiO(2), affects the mechanical
      properties of TiO(2) and SiO(2) NTFs. Our results demonstrate that the mechanical
      properties of ALD-reinforced NTFs are dominantly influenced by the mechanical
      properties of the ALD materials rather than by the compositional matching between
      ALD and nanoparticle materials. Among the three ALD materials, Al(2)O(3) ALD
      provides the best enhancement in the modulus and hardness of the NTFs.
      Interestingly, Al(2)O(3) ALD is able to enhance not only the modulus and hardness
      but also the toughness of NTFs. Our study presents an additional benefit of
      depositing nanometer scale ALD layers in NTFs; that is, we find that the hardness
      and modulus of ultrathin ALD layers (<5 nm) can be estimated from the mechanical
      properties of ALD-reinforced NTFs using a simple mixing rule. This investigation
      also provides insight into the use of nanoindentation for testing the mechanical
      properties of ultrathin ALD-reinforced NTFs.

PMID- 22968290
TI  - Is CDT truly a biomarker of disease activity in RA?

PMID- 22968289
TI  - Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the
      Bionectriaceae.
AB  - Bioactivity-directed fractionation of the organic extracts of two filamentous
      fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the
      Mycosynthetix library, led to the isolation of a new dimeric
      epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related
      analogs, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5),
      11'-deoxyverticillin A (6) and gliocladicillin A (7). The structures of compounds
      1-7 were determined by extensive NMR and HRMS analyses, as well as by comparisons
      to the literature. All compounds (1-7) were evaluated for cytotoxicity against a
      panel of human cancer cell lines, displaying IC(50) values ranging from 1.2 MUM
      to 10 nM. Compounds 1-5 were examined for activity in the NF-kappaB assay, where
      compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally,
      compounds 1, 3 and 4 were tested for EGFR inhibition using an enzymatic assay,
      while compound 3 was examined against an overexpressing EGFR(+ve) cancer cell
      line.

PMID- 22968291
TI  - Right subclavian artery aneurysm in an adolescent with a bicuspid aortic valve.
AB  - Bicuspic aortic valve is the most common congenital cardiac anomaly (Fedak et al.
      106:900-904, 2002), and it is associated with other structural anomalies of the
      aorta, such as coarctation, suggesting a common embryologic developmental
      mechanism (Mergan et al. 104:118-119, 2004). In more than a half of patients, it
      is associated with progressive dilation and aneurysm formation of the aorta
      (Warnes 89:965-966, 2003) despite normally functioning bicuspid aortic valves. In
      this context, aneurysms of the right subclavian artery are extremely rare, and
      even more so when associated with a right-sided aortic arch that has a left
      aberrant subclavian artery with a Kommerell diverticulum, as found in the
      reported case. These aneurysms represent a significant risk for thromboembolism
      and rupture, and elective surgical management should be advised, even for
      asymptomatic cases.

PMID- 22968292
TI  - Estimating global arthropod species richness: refining probabilistic models using
      probability bounds analysis.
AB  - A key challenge in the estimation of tropical arthropod species richness is the
      appropriate management of the large uncertainties associated with any model. Such
      uncertainties had largely been ignored until recently, when we attempted to
      account for uncertainty associated with model variables, using Monte Carlo
      analysis. This model is restricted by various assumptions. Here, we use a
      technique known as probability bounds analysis to assess the influence of
      assumptions about (1) distributional form and (2) dependencies between variables,
      and to construct probability bounds around the original model prediction
      distribution. The original Monte Carlo model yielded a median estimate of 6.1
      million species, with a 90 % confidence interval of [3.6, 11.4]. Here we found
      that the probability bounds (p-bounds) surrounding this cumulative distribution
      were very broad, owing to uncertainties in distributional form and dependencies
      between variables. Replacing the implicit assumption of pure statistical
      independence between variables in the model with no dependency assumptions
      resulted in lower and upper p-bounds at 0.5 cumulative probability (i.e., at the
      median estimate) of 2.9-12.7 million. From here, replacing probability
      distributions with probability boxes, which represent classes of distributions,
      led to even wider bounds (2.4-20.0 million at 0.5 cumulative probability). Even
      the 100th percentile of the uppermost bound produced (i.e., the absolutely most
      conservative scenario) did not encompass the well-known hyper-estimate of 30
      million species of tropical arthropods. This supports the lower estimates made by
      several authors over the last two decades.

PMID- 22968293
TI  - Negative mutation screening of the NOG, BMPR1B, GDF5, and FGF9 genes indicates
      further genetic heterogeneity of the facioaudiosymphalangism syndrome.
AB  - We report on a patient with a clinical phenotype showing all the features of the
      multiple synostoses syndrome or the facioaudiosymphalangism syndrome, including
      symphalangism, condunction deafness, and the typical facies. Previously, it was
      shown that this condition is genetically heterogeneous with initially mutations
      described in the NOG gene, coding for Noggin, an extracellular antagonist of bone
      morphogenetic proteins. Noggin also interacts with growth differentiation factor
      5 (GDF5), in which mutations have also been described in families with
      symphalangism. The latter is also the case for the BMP receptor BMPR1B to which
      GDF5 binds. Finally, a mutation in another growth factor, fibroblast growth
      factor 9, was found in a family with multiple synostoses syndrome. In our
      patient, we could, however, not show a causative mutation in any of these genes,
      providing evidence for further genetic heterogeneity of this syndrome.

PMID- 22968294
TI  - Novel automated screening of age-related macular degeneration.
AB  - PURPOSE: To determine the objective and quantitative hyperspectral parameters for
      distinguishing between age-related macular degeneration (AMD) and a normal
      macula. METHODS: Near-infrared hyperspectral images were taken of 71 eyes of 62
      AMD patients with exudative AMD and 21 eyes of 12 control subjects without AMD.
      The spatial information included a 480 * 321-pixel image in a 50 degrees  field
      located at the ocular fundus and a 720-950-nm-per-pixel reflectance spectrum.
      Macular vectors were determined as the average spectrum for each macula, and
      reference vectors were used as average macular vectors for healthy volunteers.
      Variations in vector length and angle were calculated based on comparison with
      the reference vector. The AMD differentiation index was a parameter that
      minimized the plot overlap between AMD patients and controls. RESULTS:
      Statistically significant differences between the AMD patients and controls were
      noted. Receiver-operating characteristic curve analysis revealed an area under
      the curve of 0.888. The appropriate threshold values were attained for the
      proposed discrimination index, including 68 % sensitivity, 95 % specificity and
      74 % accuracy. CONCLUSIONS: This study presents a simplified diagnostic index for
      the determination of age-related macular degeneration based on near-infrared
      spectra.

PMID- 22968295
TI  - Effect of citric acid on metals mobility in pruning wastes and biosolids compost
      and metals uptake in Atriplex halimus and Rosmarinus officinalis.
AB  - To assess metal mobility in pruning waste and biosolids compost (pH 6.9 and total
      concentration of metals in milligram per kilogram of Cd 1.9, Cu 132, Fe 8,513, Mn
      192, Pb 81, and Zn 313), shrubs species Atriplex halimus and Rosmarinus
      officinalis were transplanted in this substrate and irrigated with citric acid (4
      g L(-1), pH 2.9) and nutrient solution daily for 60 days. Citric acid
      significantly increased the concentrations of soluble Mn and Fe in the nutrient
      substrate solution measured by suction probes, while other metals did not vary in
      concentration (Cu and Zn) or were not observed at detectable levels (Cd and Pb).
      In plants, citric acid significantly increased the concentrations of Cu (2.7 +/-
      0.1-3.3 +/- 0.1 mg kg(-1)), Fe (49.2 +/- 5.2-76.8 +/- 6.8 mg kg(-1)), and Mn (7.2
      +/- 1.1-11.4 +/- 0.7 mg kg(-1)) in leaves of R. officinalis, whereas the
      concentration of only Mn (25.4 +/- 0.3-42.2 +/- 2.9 mg kg(-1)) was increased in
      A. halimus. Increasing Fe and Mn solubility by citric acid addition indicates the
      possibility of using it to improve plant nutrition. The mobility of metals in
      this substrate was influenced for the concentration of the metal, the degree of
      humification of organic matter and its high Fe content.

PMID- 22968296
TI  - Bosentan ameliorates the expression of fibrotic related growth factors and
      collagen-1 in diabetic mice.
AB  - OBJECTIVE: To investigate the potential beneficial effect of bosentan in
      ameliorating fibrotic agents in diabetic mice. METHODS: Male 6-week old C57BL/6
      mice were divided into 3 groups (N=20): Control group, diabetes mellitus (DM)
      group and DM-B group (diabetes with bosentan group). Streptozotocin (STZ) was
      injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting
      blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm
      that diabetes was induced in the mice. Bosentan (100mg/Kg) and placebo was given
      i.g. (intragastric administration) once a day immediately after STZ injection for
      18 weeks. The mRNA expression of tissue growth factor beta (TGF-b), connective
      tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and
      collagen-1 were evaluated by RT-PCR and real-time PCR. Differences in the data
      between the groups were compared by Student t-test for independent samples.
      RESULTS: After 18 weeks of diabetic situation, FBG of DM-B mice was significantly
      higher than that of control mice and was similar with that of DM mice (DM mice
      vs. control mice, p<0.001; DM-B vs. control mice, p<0.001; DM mice vs. DM-B mice,
      p>0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice
      was significantly higher than DM mice (p<0.01). The heart of DM-B mice also
      showed lower expression of fibrotic genes (TGF-b, CTGF and collagen-1) than DM
      mice (p<0.01). CONCLUSION: These findings indicate the potential usefulness of an
      ET receptor antagonist bosentan in the amelioration of fibrotic agents, which may
      promote tissue fibrosis. This may provide a promising therapeutical strategy for
      diabetic cardiac fibrosis.

PMID- 22968297
TI  - Clinical biomarkers of high-density lipoprotein dysfunction among middle-aged
      Turks.
AB  - OBJECTIVE: Impaired function of high-density lipoprotein (HDL) particles
      generates cardiometabolic disorders in people prone to impaired glucose tolerance
      for which clinical biomarkers need delineation. STUDY DESIGN: Prospective
      population-based study. METHODS: Totally, data of 2725 adults followed-up over
      7.3 +/- 3.0 years were analyzed by Cox regression analysis. C-reactive protein
      (CRP), complement C3 (C3), triglycerides (Trg) and HDL-cholesterol were tested to
      predict risk for incident diabetes or coronary heart disease (CHD). RESULTS:
      Beyond atherogenic dyslipidemia, high-Trg/normal HDL-cholesterol category was
      associated with elevated CRP and diabetes risk in women. Normotriglyceridemic men
      with normal HDL-cholesterol showed higher apolipoprotein A-I levels and higher
      diabetes risk than men having low HDL-cholesterol. Diabetes risk doubled in
      hypertriglyceridemic women regardless of HDL-cholesterol. Trg/HDL-C>2 in men and
      Trg>1.7 mmol/L in women were best predictors of diabetes. C3>1.3 g/L served
      additively in women alone. Regarding CHD risk, not CRP, but C3 contributed
      independently to Trg/HDL>2 in men [RR 2.46 (95% CI 1.33; 4.53)]; a high ratio was
      merely additive to elevated CRP in women. Among five cut-off values, predictive
      values for diabetes were highest for CRP >2.5 mg/L in men, Trg>1.7 mmol/L and
      C3>1.3 g/dL in women. CONCLUSION: Trg/HDL-C ratio >2 and/or CRP >2.5 mg/L in men
      and Trg>1.7 mmol/L+C3>1.3 g/dL in women are most appropriate markers regarding
      impaired antiinflammatory or atheroprotective HDL function. In
      normotriglyceridemic men with normal HDL-cholesterol levels, diabetes risk may be
      elevated due to presumably dysfunctional apolipoprotein A-I.

PMID- 22968298
TI  - Coronary artery ectasia is associated with atrial electrical and mechanical
      dysfunction: an observational study.
AB  - OBJECTIVE: The aim of our study was to investigate total atrial conduction time
      and left atrial (LA) mechanical function in patients with isolated coronary
      artery ectasia (ICAE). METHODS: Sixty patients with ICAE without any visible
      coronary stenosis were enrolled to this cross-sectional observational study. The
      control group consisted of 40 age- and gender-matched patients. Left atrial
      mechanical functions were measured by the method of discs in the apical-four
      chamber echocardiographic view. LA mechanical function parameters were
      calculated. P wave dispersion was measured on electrocardiography (ECG). The
      total atrial conduction time (PA-tissue Doppler imaging (TDI) duration) was
      assessed by measuring the time interval between the beginning of the P wave on
      the surface ECG and point of the peak A wave on TDI from LA lateral wall just
      over the mitral annulus. Student t, Mann-Whitney U, Pearson's, and Spearman's
      correlation analysis and multiple regression analysis were used for statistical
      analysis. RESULTS: The clinical and laboratory characteristics were similar in
      two groups. Both groups were similar in terms of Vmax and LA total emptying
      volume (29.0 +/- 7.3 vs. 31.9 +/- 6.5 mL/m2, p=0.082 and 19.9 +/- 5.1 vs. 20.0 +/
      5.2 mL/m2, p=0.821). However, LA passive emptying volume and LA passive emptying
      fraction were significantly decreased with ICAE patients (11.1 +/- 3.2 vs. 13.5
      +/- 3.8 ml/m2, p=0.005 and 35.2 +/- 7.2 vs. 47.8 +/- 9.4 mL/m2, p<0.001). But LA
      active emptying volume and LA active emptying fraction were significantly
      increased in ICAE patients (9.1 +/- 2.6 vs. 6.4 +/- 3.0 mL/m2, p<0.001 and 45.3
      +/- 8.1 vs. 40.7 +/- 6.7 mL/m2, p=0.002). PA-TDI duration was measured
      significantly higher in patients with ICAE than control group (131.8 +/- 5.7 vs.
      114.4 +/- 9.1 ms, p<0.001). Multiple linear regression analyses showed that
      ectatic segment number was an independent factor of PA-TDI duration (beta=0.581,
      95% CI=4.046-6.295, p<0.001). CONCLUSION: Our study demonstrated presence of LA
      electrical and mechanical dysfunction in patients with ICAE. LA dysfunction may
      be associated with cardiac pathologies as arrhythmias, decrease in cardiac output
      and congestive failure.

PMID- 22968299
TI  - Prevalence and clinical features of atrial fibrillation in diabetic neuropathy: a
      cross-sectional, observational study.
AB  - OBJECTIVE: This cross-sectional, observational study investigated prevalence and
      clinical features of atrial fibrillation (AF) in diabetic patient groups with or
      without autonomic neuropathy. METHODS: One hundred and fourteen consecutive
      patients with pharmacologically treated type-II diabetes mellitus were enrolled
      for this study in our institution between January 2010 and December 2010. All
      patients underwent 12-lead electrocardiography on the day of enrollment for AF
      detection. All diabetic patients underwent neurologic examination for the
      presence of diabetic autonomic neuropathy (DAN). Following clinical evaluation,
      sympathetic skin responses (SSR) and RR interval variability (RRIV) analysis were
      used for the detection of autonomic neurologic involvement. Patients were divided
      into two groups according to presence (Group 1) or absence (Group 2) of DAN.
      Patient groups with or without DAN were compared for AF occurrence. Continuous
      and categorical data were compared with independent samples t- test and Chi
      square statistical tests respectively. RESULTS: Atrial fibrillation prevalence
      was 24% (n=29) in study population. Diabetic autonomic neuropathy was diagnosed
      in 47 (39%) patients. Basal characteristics of patients with or without DAN were
      comparable except glycosylated hemoglobin A (HbA1c) levels. HbA1c levels were
      found significantly higher in patients with DAN. Atrial fibrillation was
      diagnosed in 14 patients in Group 1 and in 15 patients in Group 2. Significantly
      increased AF prevalence (31.9% vs. 20.8%, p=0.014, in groups with and without DAN
      respectively) was observed in patient group with diabetic autonomic neuropathy.
      CONCLUSION: The results of this study demonstrated an increased prevalence of AF
      in patients with diabetic autonomic neuropathy compared with non-neuropathic,
      diabetic patients. Further investigation of this relation with prospective
      studies is needed to demonstrate a causal relationship between diabetic autonomic
      neuropathy and AF.

PMID- 22968300
TI  - Increased gamma-glutamyl transferase level is associated with absence of coronary
      collateral vessels in patients with acute coronary syndrome: an observational
      study.
AB  - OBJECTIVE: Elevated serum gamma-glutamyl transferase (GGT) level has been
      proposed as a risk factor for coronary artery disease and is associated with poor
      clinical outcome in acute coronary syndrome (ACS). We aimed to evaluate the
      relationship between GGT level and presence of coronary collateral vessels (CCV)
      patients with ACS. METHODS: We evaluated 178 patients with ACS in this cross
      sectional-observational study. Traditional laboratory and clinical parameters and
      serum GGT levels were measured. All patients underwent coronary angiography on
      the first day after admission and patients who had >80% stenosis of coronary
      artery were included in the study. The CCVs graded according to the Rentrop
      scoring system and Rentrop 0, 1, 2 and 3 were determined in respectively 76
      (42.7%), 32 (18.0%), 33 (18.5%), and 37 (20.8%) patients. Rentrop grade 0 was
      accepted as no CCV development (Group 1), Rentrop grades 1-2-3 were accepted as
      presence of CCV development (Group 2). Statistical analysis was performed using
      independent-samples t , Mann-Whitney U and Chi-squared tests, logistic regression
      and receiver operator curve analyses. RESULTS: Mean age was 62 +/- 10 years and
      134 (75.3%) of patients were male. Group 1 consisted of 76 (42.7%) patients and
      Group 2 consisted of 102 (57.3%) patients. The median and minimum-maximum values
      of serum GGT were 33.5 (8-128) U/L for Group 1 and 23 (2-83) U/L for Group 2.
      Absence of CCV was significantly associated with high levels of GGT (p<0.001),
      alanine-aminotransferase (p=0.001), glucose (p=0.011) and low levels of total
      protein (p=0.020). At multivariate analysis, high levels of GGT were independent
      predictors of absence of CCV (OR=0.953, 95%CI 0.912-0.996, p=0.031). CONCLUSION:
      High levels of GGT on admission were associated with absence of CCV in patients
      with ACS.

PMID- 22968301
TI  - Relationship between cardiac troponin-T and right ventricular Tei index in
      patients with hemodynamically stable pulmonary embolism: an observational study.
AB  - OBJECTIVE: The role of increased troponin level in risk stratification of acute
      pulmonary embolism (PE) is well documented. However, relation between right
      ventricular (RV) myocardial performance (Tei) index and cardiac troponin-T (cTn
      T) has not been well investigated. The purpose of this observational prospective
      study was to assess the relationship between the RV Tei index and cTn-T in
      patients with acute normotensive PE. METHODS: Thirty-eight patients with acute PE
      diagnosed by computed spiral tomography pulmonary angiography were enrolled to
      this prospective observational study. All study population underwent a
      comprehensive echocardiographic study including tissue Doppler imaging within
      first 12 hours of admission. cTn-T levels were measured on admission. Follow-up
      echocardiography was performed routinely at the 7th day of hospitalization.
      Echocardiographic evaluation was repeated at 90 days in patients with
      insufficient improvement of RV Tei index. The difference between the baseline and
      follow-up data was analyzed using the paired sample t-test or Wilcoxon test
      according to normality of distribution. RESULTS: The mean of the RV Tei index was
      0.46 +/- 0.14 and the mean systolic pulmonary artery pressure (sPAP) was 40 +/-
      20 mmHg. Increased cTn-T level was detected in 37% of the patients (normal value
      0.01< ng/mL). Significant correlations were observed between RV Tei index and
      sPAP with cTn-T levels (r=0.467 and r=0.468, p<0.001, respectively). In logistic
      regression analysis, RV Tei index was associated with positive cTn-T values (OR
      136, 95% CI: 1.3-14657, p=0.039). After the anticoagulant treatment, RV Tei index
      and sPAP were significantly improved. CONCLUSION: RV Tei index is frequently
      impaired in patients with acute PE and a significant recovery is seen after the
      treatment. Therefore, RV Tei index may be used both the diagnosis of RV
      dysfunction and the assessment of treatment effectiveness. RV Tei index is may
      predict myocardial injury in PE.

PMID- 22968302
TI  - Cardiac responses to long duration and high magnitude +Gz exposure in pilots: an
      observational study.
AB  - OBJECTIVE: In military aviation, high performance aircraft pilots are exposed to
      +Gz acceleration at longer durations and higher magnitude than
      transport/helicopter pilots. The purpose of this study was to reveal the negative
      or positive cardiac responses to this occupational high +Gz exposure. METHODS:
      Our study design was cross-sectional and observational. We have evaluated 21
      echocardiographic parameters of 63 pilots who applied for aircrew periodic
      medical examination. Of 63 pilots, 33 were grouped as high performance aircraft
      pilots group (Group A) and 30 were grouped as control group (Group B) whose
      aircraft type was transport or helicopter. Means of demographic and
      echocardiography parameters between two groups were compared statistically with
      Student's t-test, Mann- Whitney U or Chi-square test as appropriate. RESULTS:
      Among all echocardiographic parameters, mean TV A (tricuspid valve peak velocity
      during late diastolic filling) was significantly higher and TV E (peak velocity
      during early diastolic filling)/ A ratio was significantly lower for Group A
      pilots (p<0.05). In Group A pilots, mean TV A and TV E/A ratio were (52.12 +/-
      13.85) and (1.36 +/- 0.30) respectively. In Group B pilots, mean TV A and TV E/A
      ratio were (42.61 +/- 6.42) and (1.53 +/- 0.20) respectively (p=0.001 for TVA and
      p=0.005 for TV E/A). Mean pulmonary artery pressure (PAP) of Group A pilots
      (32.04 +/- 9.09) was higher than Group B pilots (28.76 +/- 7.9) but it was not
      statistically significant (p>0.05). CONCLUSION: We conclude that according to the
      results of our study, long term +Gz exposure has no effects on cardiac
      morphologic and systolic functions but has effects on right ventricular diastolic
      functions. We have considered that these effects may be a result of chronic +Gz
      adaptation or high PAP levels.

PMID- 22968303
TI  - Psychometric properties of the Persian version of the Duke University Religion
      Index (DUREL): a study on Muslims.
AB  - The aim of this study was translation and validation of the Duke University
      Religion Index in Iranian Muslims. The study was performed in two stages. In the
      first stage, 1,762 college students from Qazvin city with an average age of 21.2
      years participated in the study. In the second phase, 796 college students with
      an average age of 23.7 were recruited from Tehran. A demographic questionnaire,
      Santa Clara Strength Faith questionnaire (SCSORF), and Duke Religion Index
      (DUREL) were administered. Cultural adaptation of these measures was performed by
      a forward-backward translation technique. Test-retest reliability and intraclass
      correlation coefficients (ICC) were used for assessing reliability. Convergent
      validity was measured by Spearman correlation between DUREL and SCSORF.
      Explanatory and confirmatory factor analyses (EFA and CFA) evaluated the factor
      structure. Results showed that the scale is reliable. Cronbach's alpha ranged
      from 0.866 to 0.921 and ICC ranged from 0.937 to 0.991. Correlations between
      DUREL and SCSORF were also strong (ranging from 0.62 to 0.79). Results obtained
      from CFA and EFA confirmed one-dimension for the DUREL. Thus, the DUREL appears
      to be a proper measure for assessing religiosity among Iranian Muslims. Further
      testing of the scale among minorities and those with special health-related
      conditions is suggested.

PMID- 22968305
TI  - Association of physical activity, fitness, and race: NHANES 1999-2004.
AB  - PURPOSE: Regular physical activity (PA) can be used to improve cardiorespiratory
      fitness (CRF). Previous research has shown differences in CRF (VO2max) among
      racial groups, but it is unclear how much of these differences can be explained
      by PA. Thus, we sought to examine the association between PA and CRF in different
      racial groups. METHODS: As a part of the National Health and Nutrition
      Examination Survey (1999-2004), 3115 adults (18-49 yr) completed a submaximal
      graded treadmill exercise test to estimate VO2max. Independent variables were
      demographics (race, education, sex, partner status, and waist circumference),
      behavioral measures (smoking and alcohol consumption), self-reported PA from
      three domains (leisure-time, domestic, and transportational PA (MET x min x wk(
      1)), and the proportion of PA at a vigorous intensity (VMET). CRF was the
      dependent variable. Multiple linear regression was performed using SUDAAN
      statistical software. RESULTS: Results indicated that VO2max was significantly
      higher for Mexican Americans (40.9 T 0.5 mL x kg(-1) x min(-1)) and non-Hispanic
      whites (40.2 +/- 0.3 mL x kg(-1) x min(-1)) compared with non-Hispanic blacks
      (37.9 +/- 0.6 mL x kg(-1) x min(-1)) (P = 0.01). Demographics including race
      explained 18.5% of the variance in VO2max, with race being significant (P < 0.01)
      in the model. When PA was added to the model, the explained variance in VO2max
      increased to 19.3% (P = 0.001). VMET was more predictive of VO2max than total PA,
      and the model including VMET explained 20.4% of the variance in VO2max. Race
      remained a significant, independent predictor of VO2max after VMET and overall PA
      were added to the model. CONCLUSION: Race, PA, and exercise intensity are
      important factors in explaining differences in CRF. After accounting for
      demographics, PA, and VMET, a large proportion of the variance in CRF remains
      unexplained. Thus, other factors should also be considered when examining
      racial/ethnic differences in CRF.

PMID- 22968306
TI  - Protein supplementation during resistance-type exercise training in the elderly.
AB  - INTRODUCTION: Resistance training has been well established as an effective
      treatment strategy to increase skeletal muscle mass and strength in the elderly.
      We assessed whether dietary protein supplementation can further augment the
      adaptive response to prolonged resistance-type exercise training in healthy
      elderly men and women. METHODS: Healthy elderly men (n = 31, 70 +/- 1 yr) and
      women (n = 29, 70 +/- 1 yr) were randomly assigned to a progressive, 24-wk
      resistance-type exercise training program with or without additional protein
      supplementation (15 g.d-1). Muscle hypertrophy was assessed on a whole-body Dual
      energy X-ray absorptiometry (DXA), limb (computed tomography), and muscle fiber
      (biopsy) level. Strength was assessed regularly by 1-repetition maximum (RM)
      strength testing. Functional capacity was assessed with a sit-to-stand and
      handgrip test. RESULTS: One-RM strength increased by 45% +/- 6% versus 40% +/- 3%
      (women) and 41% +/- 4% versus 44% +/- 3% (men) in the placebo versus protein
      group, respectively (P < 0.001), with no differences between groups. Leg muscle
      mass (women, 4% +/- 1% vs 3% +/- 1%; men, 3% +/- 1% vs 3% +/- 1%) and quadriceps
      cross-sectional area (women, 9% +/- 1% vs 9% +/- 1%; men, 9% +/- 1% vs 10% +/-
      1%) increased similarly in the placebo versus protein groups (P < 0.001). Type II
      muscle fiber size increased over time in both placebo and protein groups (25% +/-
      13% vs 30% +/- 9% and 23% +/- 12% vs 22% +/- 10% in the women and men,
      respectively). Sit-to-stand improved by 18% +/- 2% and 19% +/- 2% in women and
      men, respectively (P < 0.001). CONCLUSION: Prolonged resistance-type exercise
      training increases skeletal muscle mass and strength, augments functional
      capacity, improves glycemia and lipidemia, and reduces blood pressure in healthy
      elderly men and women. Additional protein supplementation (15 g.d-1) does not
      further increase muscle mass, strength, and/or functional capacity.

PMID- 22968307
TI  - Effect of an antipronation foot orthosis on ankle and subtalar kinematics.
AB  - INTRODUCTION/PURPOSE: The aim of this study was to describe the effect of an
      antipronation foot orthosis on motion of the heel relative to the leg and explore
      the individual contributions of the ankle and subtalar joints to this effect.
      METHODS: Five subjects were investigated using invasive intracortical pins to
      track the movement of the tibia, talus, and calcaneus during walking with and
      without a foot orthosis. RESULTS: The antipronation foot orthosis produced small
      and unsystematic reductions in eversion and abduction of the heel relative to the
      leg at various times during stance. Changes in calcaneus-tibia motion were
      comparable with those described in the literature (1 degrees -3 degrees ).
      Changes at both the ankle and subtalar joints contributed to this orthotic
      effect. However, the nature and scale of changes were highly variable between
      subjects. Peak angular position, range of motion, and angular velocity in frontal
      and transverse planes were affected to different degrees in different subjects.
      In some cases, changes occurred mainly at the ankle; in other cases, changes
      occurred mainly at the subtalar joint. CONCLUSION: The changes in ankle and
      subtalar kinematics in response to the foot orthosis contradict existing orthotic
      paradigms that assume that changes occur only at the subtalar joint. The
      kinematic changes due to the orthosis are indicative of a strong interaction
      between the often common function of the ankle and subtalar joints.

PMID- 22968308
TI  - Eccentric exercise increases satellite cell content in type II muscle fibers.
AB  - INTRODUCTION: Satellite cells (SCs) are of key importance in skeletal muscle
      tissue growth, repair, and regeneration. A single bout of high-force eccentric
      exercise has been demonstrated to increase mixed muscle SC content after 1-7 d of
      postexercise recovery. However, little is known about fiber type-specific changes
      in SC content and their activation status within 24 h of postexercise recovery.
      METHODS: Nine recreationally active young men (23 +/- 1 yr) performed 300
      eccentric actions of the knee extensors on an isokinetic dynamometer. Skeletal
      muscle biopsies from the vastus lateralis were collected preexercise and 24 h
      postexercise. Muscle fiber type-specific SC content and the number of activated
      SCs were determined by immunohistochemical analyses. RESULTS: There was no
      difference between Type I and Type II muscle fiber SC content before exercise. SC
      content significantly increased 24 h postexercise in Type II muscle fibers (from
      0.085 +/- 0.012 to 0.133 +/- 0.016 SCs per fiber, respectively; P < 0.05),
      whereas there was no change in Type I fibers. In accordance, activation status
      increased from preexercise to 24 h postexercise as demonstrated by the increase
      in the number of DLK1+ SCs in Type II muscle fibers (from 0.027 +/- 0.008 to
      0.070 +/- 0.017 SCs per muscle fiber P < 0.05). Although no significant changes
      were observed in the number of Ki-67+ SCs, we did observe an increase in the
      number of proliferating cell nuclear antigen-positive SCs after 24 h of
      postexercise recovery. CONCLUSION: A single bout of high-force eccentric exercise
      increases muscle fiber SC content and activation status in Type II but not Type I
      muscle fibers.

PMID- 22968304
TI  - Virtual screening for LPA2-specific agonists identifies a nonlipid compound with
      antiapoptotic actions.
AB  - Lysophosphatidic acid (LPA) is a highly potent endogenous lipid mediator that
      protects and rescues cells from programmed cell death. Earlier work identified
      the LPA2 G protein-coupled receptor subtype as an important molecular target of
      LPA mediating antiapoptotic signaling. Here we describe the results of a virtual
      screen using single-reference similarity searching that yielded compounds 2-((9
      oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (NSC12404), 2-((3-(1,3-dioxo-1H
      benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), 4,5-dichloro
      2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (H2L5547924), and 2-((9,10-dioxo
      9,10-dihydroanthracen-2-yl)carbamoyl) benzoic acid (H2L5828102), novel nonlipid
      and drug-like compounds that are specific for the LPA2 receptor subtype. We
      characterized the antiapoptotic action of one of these compounds, GRI977143,
      which was effective in reducing activation of caspases 3, 7, 8, and 9 and
      inhibited poly(ADP-ribose)polymerase 1 cleavage and DNA fragmentation in
      different extrinsic and intrinsic models of apoptosis in vitro. Furthermore,
      GRI977143 promoted carcinoma cell invasion of human umbilical vein endothelial
      cell monolayers and fibroblast proliferation. The antiapoptotic cellular
      signaling responses were present selectively in mouse embryonic fibroblast cells
      derived from LPA(1&2) double-knockout mice reconstituted with the LPA2 receptor
      and were absent in vector-transduced control cells. GRI977143 was an effective
      stimulator of extracellular signal-regulated kinase 1/2 activation and promoted
      the assembly of a macromolecular signaling complex consisting of LPA2, Na+ - H+
      exchange regulatory factor 2, and thyroid receptor interacting protein 6, which
      has been shown previously to be a required step in LPA-induced antiapoptotic
      signaling. The present findings indicate that nonlipid LPA2-specific agonists
      represent an excellent starting point for development of lead compounds with
      potential therapeutic utility for preventing the programmed cell death involved
      in many types of degenerative and inflammatory diseases.

PMID- 22968309
TI  - Curvilinear dose-response relationship of carbohydrate (0-120 g.h(-1)) and
      performance.
AB  - BACKGROUND: There is a lack of consensus regarding the optimal range of
      carbohydrate (CHO) ingestion rates recommended for endurance athletes. PURPOSE:
      This study investigated the relationship between CHO dose and cycling time trial
      performance to identify an optimal range of CHO ingestion rates for endurance
      performance. METHODS: Fifty-one cyclists and triathletes (28 +/- 7 yr, mean +/-
      SD) across four research sites completed four trials. Each trial consisted of a 2
      h constant load ride at 95% of the workload that elicited a 4-mmol.L(-1) blood
      lactate concentration immediately followed by a computer-simulated 20-km time
      trial, which subjects were asked to complete as quickly as possible. Twelve CHO
      electrolyte (18 mmol.L(-1) Na, 3 mmol.L(-1) K, and 11 mmol.L(-1) Cl) beverages
      (three at each site) were tested in a double-blind manner, providing subjects 10,
      20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 g CHO (1:1:1 glucose-fructose
      maltodextrin) per hour during the 2-h constant load ride at a fluid intake rate
      of 1 L.h(-1). All subjects also consumed a noncaloric placebo on one
      counterbalanced test occasion. Data were natural log transformed, subjected to a
      mixed-model analysis, and are reported as adjusted treatment means. RESULTS: We
      estimate incremental performance improvements of 1.0%, 2.0%, 3.0%, 4.0%, and 4.7%
      at 9, 19, 31, 48, and 78 g.h, respectively, with diminishing performance
      enhancement seen at CHO levels >78 g.h(-1). CONCLUSIONS: CHO beverage ingestion
      and endurance (~160 min) performance appear to be related in a curvilinear dose
      response manner, with the best performance occurring with a CHO (1:1:1 glucose
      fructose-maltodextrin) ingestion rate of 78 g.h(-1).

PMID- 22968310
TI  - Effect of spatial and temporal cues on athletic pacing in schoolchildren.
AB  - PURPOSE: To compare pacing and performance of schoolchildren between running
      tasks where the end point was defined in units of either distance or time.
      METHODS: Thirty-eight schoolchildren (age = 12.6 +/- 0.5 yr, mass = 46.2 +/- 7.5
      kg, stature = 150 +/- 7 cm) first performed a best-effort 750-m running task on a
      150-m running track. The schoolchildren were split into two groups, matched for
      sex, age, and running performance, before completing the second running trial.
      One group repeated the 750-m running task (distance-distance group), whereas the
      other completed a running task to a time that had been matched to their previous
      750-m performance (distance-time group). Pace was measured every 10% segment
      throughout each run. RESULTS: No difference between trials in average running
      speed was found among the distance-distance group (13.64 +/- 1.59 vs. 13.68 +/-
      1.62 km.h(-1), P > 0.05); however, the distance-time group were slower during the
      time task compared with during the distance task (13.84 +/- 1.61 vs. 13.37 +/-
      1.57 km.h(-1), P < 0.005). There was no difference in pacing pattern between
      trials among the distance-distance group (P > 0.05), but the distance-time group
      exhibited a slower overall slower pace with no end spurt (P < 0.0001). During the
      time task, children looked at their watches more frequently the nearer they got
      to the end point (rho = 0.933, P < 0.0001). CONCLUSIONS: Schoolchildren find it
      easier to use spatial cues during a pacing task compared with temporal cues.
      Running pace in all trials followed a classic U-shaped pattern; however, lap-by
      lap oscillations in pacing substrategies were also evident, which may be a
      psychological coping strategy.

PMID- 22968311
TI  - Peak oxygen uptake and physical activity in 13- to 18-year-olds: the Young-HUNT
      study.
AB  - PURPOSE: The present study describes the distribution of cardiorespiratory
      fitness (VO2peak) in a large sample of healthy adolescents and the associations
      between VO2peak, self-reported physical activity, and a selection of conventional
      markers for future cardiovascular health. METHODS: In a substudy of the Young
      HUNT study in Norway, 570 adolescents (289 girls and 281 boys) 13-18 yr. old were
      tested for directly measured VO2peak. Blood pressure, resting heart rate, height,
      weight, and waist circumference was measured by standardized procedures. Data
      about physical activity and pubertal development were obtained using self
      administered questionnaires. General linear modeling and ANOVA were used to
      examine the relationships between VO2peak and age, physical activity, and
      cardiovascular risk factors. RESULTS: The mean T SD VO2peak was 183.9 +/- 24.6 mL
      x kg(-0.67) x min(-1) (49.2 mL x kg(-0.67) x min(-1)) in girls and 235.1 +/- 35.3
      mL x kg(-0.67) x min(-1) (59.5 mL x kg(-0.67) x min(-1)) in boys. Absolute
      VO2peak (L x min(-1)) was consistently higher in older age groups in both sexes
      (P trend < 0.001). VO2peak allometrically scaled to body mass (mL x kg(-0.67) x
      min(-1)) was similar across the age groups in girls (i.e., difference between 13-
      to 14-yr-olds and 17- to 18-yr-olds = -3.2 mL x kg(-0.67) x min(-1), 95%
      confidence interval = 3.8 to -10.1) and slightly higher in the older age groups
      in boys (i.e., difference between 13- to 14-yr-olds and 15- to 16-yr-olds = -31.0
      mL x kg(-0.67) x min(-1), 95% confidence interval = -22.0 to -40.1). Physical
      activity was positively associated with VO2peak in all sex and age groups.
      Quartiles of VO2peak were inversely associated with resting heart rate (P trend =
      0.004) in both sexes and body mass index (P trend = 0.004) and waist
      circumference (P trend = 0.006) in boys. CONCLUSION: Although VO2peak was
      generally high across the age groups, VO2peak was higher in physically active
      adolescents of both sexes and physical activity in accordance with the
      recommended level may be sufficient to maintain or even increase VO2peak through
      adolescence.

PMID- 22968312
TI  - Association of low aerobic fitness with hyperfiltration and albuminuria in men.
AB  - PURPOSE: The purpose of this study was to evaluate the association of low aerobic
      fitness (AF), a quantitative phenotype primarily modified by physical activity,
      with the earlier markers of chronic kidney disease (CKD). METHODS: Maximum oxygen
      uptake (VO2max), the best index of AF, was estimated in an apparently healthy
      population of 34,769 adults without known history of diabetes and/or
      hypertension, and its association with renal function and albuminuria was
      analyzed retrospectively. VO2max was estimated using a cycle ergometer.
      Glomerular filtration rate was estimated with the Modification of Diet in Renal
      Disease Study equation. Glomerular hyperfiltration was defined as estimated
      glomerular filtration rate above the age- and sex-specific 97.5th percentile.
      Albuminuria was detected with dipstick urinalysis on fast morning urine and
      defined as >=1+. RESULTS: VO2max levels were negatively correlated with the odds
      ratios of glomerular hyperfiltration in men (Ptrend = 0.039), not in women.
      VO2max was associated with glomerular hyperfiltration in young men (<= the median
      age; Ptrend < 0.001), but not in old men. VO2max levels were negatively
      correlated with the odds ratio of albuminuria in men (Ptrend < 0.001), but not in
      women. These findings suggest that low AF may be associated with earlier markers
      of CKD in men. This association was not observed in women. CONCLUSION: From the
      results of this study, it can be concluded that low AF may be a possible
      independent, modifiable risk factor for CKD in men.

PMID- 22968313
TI  - Step count targets corresponding to new physical activity guidelines for the
      early years.
AB  - PURPOSE: New physical activity guidelines recommend that children age 3-4 yr
      should accumulate at least 180 min of physical activity at any intensity spread
      throughout the day, including progression toward at least 60 min of energetic
      play by 5 yr of age. Step count targets corresponding to these recommendations
      will help practitioners and researchers monitor physical activity. METHODS: One
      hundred thirty-three preschoolers were instructed to wear accelerometers for
      seven consecutive days. Activity and step count data were recorded in 3-s epochs.
      Step count targets equivalent to physical activity recommendations were derived
      using prediction equations from regression analyses. Receiver operating curve
      analyses were conducted to compare the sensitivity and specificity of the derived
      thresholds as well as a range of other targets. RESULTS: The daily step count
      target derived for 180 min of physical activity of any intensity was 6013 +/- 88,
      whereas the target for 180 min of physical activity of any intensity including at
      least 60 min of moderate-to-vigorous physical activity was 6191 +/- 103. The
      smallest discrepancy between days meeting physical activity guidelines and step
      count targets was found with a 6000-step-per-day target. Receiver operating
      curves confirmed a balanced sensitivity and specificity of this target.
      CONCLUSIONS: On the basis of our data, we suggest that a new step count target of
      6000 steps per day should be used to determine whether 3- to 5-yr-old children
      are meeting physical activity recommendations.

PMID- 22968314
TI  - Processing of atmospheric polycyclic aromatic hydrocarbons by fog in an urban
      environment.
AB  - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants in the
      atmosphere, predominantly known for their toxicity. Although there has been
      substantial work on the atmospheric degradation of PAH, little is known about how
      the presence of atmospheric droplets (e.g., a fog cloud) affects the fate of PAH.
      In order to assess the processing of PAH and their corresponding oxidation
      products during a fog event, two field-sampling campaigns in Fresno, CA and
      Davis, CA were conducted. The simultaneous evaluation of concentrations of the
      PAH and oxygenated polycyclic aromatic compounds (OPAC) in the gas phase,
      particulate matter and fog water droplets before, during and after fog allows for
      the characterization of transformative and transport processes in a fog cloud. By
      tracking the ratio of OPAC to PAH in the individual atmospheric phases, two major
      polycyclic aromatic compounds-processing pathways can be identified: (i) the
      dissolution of OPAC from particulate matter and (ii) the uptake and oxidation of
      PAH in the fog water droplets. Wet deposition steadily decreases the pollutant
      concentration in the fog cloud droplets during a fog event; however, uptake and
      concentration via evaporative water loss upon the dissipation of a fog cloud
      cause an increase in the atmospheric pollutant concentration.

PMID- 22968316
TI  - Contrasting preferences of N and P substituted heteroaromatics towards metal
      binding: probing the regioselectivity of Li+ and Mg2+ binding to (CH)(6-m
      n)N(m)P(n).
AB  - High level ab initio and hybrid DFT methods have been employed to investigate the
      interactions of metal ions (Li(+) and Mg(2+)) with N and P substituted six
      membered heteroaromatics (CH)(6-m-n)N(m)P(n). The binding energy (BE) of metal
      ions with the N and P substituted heteroaromatics has been computed at the
      CCSD(T)/cc-pVTZ//MP2/cc-pVTZ level with counterpoise correction. In the present
      study we systematically examined the preferential modes of binding of metal ions
      to the heteroaromatics. N-Substituted heteroaromatics show a strong preference
      for cation-sigma mode of binding whereas the P-substituted heteroaromatics prefer
      cation-pi mode of binding with the metal ions. Energy decomposition analysis
      (EDA) using the DFT-SAPT scheme has been carried out to analyse the contribution
      of various energy components to the BE. The results illustrate that for the
      cation-pi complexes, the contribution of the induction term is more whereas in
      the case of cation-sigma there is a competition between induction and
      electrostatic terms in the interaction energy.

PMID- 22968315
TI  - Arsenic exposure and cardiovascular disease: an updated systematic review.
AB  - In epidemiologic studies, high-chronic arsenic exposure has been associated with
      cardiovascular disease, despite methodological limitations. At low-moderate
      arsenic levels, the evidence was inconclusive. Here, we update a previous
      systematic review (Am J Epidemiol 2005;162:1037-49) examining the association
      between arsenic exposure and cardiovascular disease. Eighteen studies published
      since 2005 were combined with 13 studies from the previous review. We calculated
      pooled relative risks by comparing the highest versus the lowest exposure
      category across studies. For high exposure (arsenic in drinking water > 50
      MUg/L), the pooled relative risks (95 % confidence interval) for cardiovascular
      disease, coronary heart disease, stroke, and peripheral arterial disease were
      1.32 (95 % CI:1.05-1.67), 1.89 (95 % CI:1.33-2.69), 1.08 (95 % CI:0.98-1.19), and
      2.17 (95 % CI:1.47-3.20), respectively. At low-moderate arsenic levels, the
      evidence was inconclusive. Our review strengthens the evidence for a causal
      association between high-chronic arsenic exposure and clinical cardiovascular
      endpoints. Additional high quality studies are needed at low-moderate arsenic
      levels.

PMID- 22968317
TI  - A simple route to synthesis of branched and cross-linked polymers with clickable
      moieties by photopolymerization.
AB  - Lightly branched, hyperbranched and cross-linked polymers with clickable sites
      were synthesized via a modified version of self-condensing photoinitiated
      copolymerization of methyl acrylate (MA) with propargyl acrylate (PA). The method
      is based on the use of a PA monomer containing two polymerizable groups, namely
      acrylate and propargyl groups with different reactivities in photoinitiated free
      radical copolymerization with MA.

PMID- 22968318
TI  - Alterations in cerebral oxygen metabolism after traumatic brain injury in
      children.
AB  - Traumatic brain injury (TBI) is the most common cause of acquired disability in
      children. Metabolic defects, and in particular mitochondrial dysfunction, are
      important contributors to brain injury after TBI. Studies of metabolic
      dysfunction are limited, but magnetic resonance methods suitable for use in
      children are overcoming this limitation. We performed noninvasive measurements of
      cerebral blood flow and oxygen metabolic index (OMI) to assess metabolic
      dysfunction in children with severe TBI. Cerebral blood flow is variable after
      TBI but hypoperfusion and low OMI are predominant, supporting metabolic
      dysfunction. This finding is consistent with preclinical and adult clinical
      studies of brain metabolism and mitochondrial dysfunction after TBI.

PMID- 22968319
TI  - A genetic polymorphism for translocator protein 18 kDa affects both in vitro and
      in vivo radioligand binding in human brain to this putative biomarker of
      neuroinflammation.
AB  - Second-generation radioligands for translocator protein (TSPO), an inflammation
      marker, are confounded by the codominant rs6971 polymorphism that affects binding
      affinity. The resulting three groups are homozygous for high-affinity state (HH),
      homozygous for low-affinity state (LL), or heterozygous (HL). We tested if in
      vitro binding to leukocytes distinguished TSPO genotypes and if genotype could
      affect clinical studies using the TSPO radioligand [(11)C]PBR28. In vitro binding
      to leukocytes and [(11)C]PBR28 brain imaging were performed in 27 human subjects
      with known TSPO genotype. Specific [(3)H]PBR28 binding was measured in prefrontal
      cortex of 45 schizophrenia patients and 47 controls. Leukocyte binding to PBR28
      predicted genotype in all subjects. Brain uptake was ~40% higher in HH than HL
      subjects. Specific [(3)H]PBR28 binding in LL controls was negligible, while HH
      controls had ~80% higher binding than HL controls. After excluding LL subjects,
      specific binding was 16% greater in schizophrenia patients than controls. This
      difference was insignificant by itself (P=0.085), but was significant after
      correcting for TSPO genotype (P=0.011). Our results show that TSPO genotype
      influences PBR28 binding in vitro and in vivo. Correcting for this genotype
      increased statistical power in our postmortem study and is recommended for in
      vivo positron emission tomography studies.

PMID- 22968320
TI  - Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate
      inflammation after intracerebral hemorrhage.
AB  - The inflammatory response plays a pivotal role in propagating injury of
      intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with
      antidiabetic effect and may also have antiinflammatory properties. Despite
      consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP
      1R), mechanisms in the brain remain unclear. We investigated the effect of a long
      acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from
      dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary
      outcomes were cerebral edema formation, neurobehavior, and inflammatory
      parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated
      protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were
      administered to examine the mechanisms of action. Liraglutide suppressed
      neuroinflammation, prevented brain edema and neurologic deficit following ICH,
      which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation
      inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R
      inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed
      salutary effects on primary outcomes that were reversed by AMPK phosphorylation
      inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co
      administration reversed liraglutide-mediated AMPK phosphorylation and
      antiinflammatory effects. Liraglutide exerted duals actions and the
      antiinflammatory effects are partially mediated by its metabolite in a
      phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation
      may weaken the metabolite-mediated effects.

PMID- 22968321
TI  - Regulatory T cells accumulate and proliferate in the ischemic hemisphere for up
      to 30 days after MCAO.
AB  - Local and peripheral immune responses are activated after ischemic stroke. In our
      present study, we investigated the temporal distribution, location, induction,
      and function of regulatory T cells (Tregs) and the possible involvement of
      microglia, macrophages, and dendritic cells after middle cerebral artery
      occlusion (MCAO). C57BL/6J and Foxp3(EGFP) transgenic mice were subjected to 30
      minutes MCAO. On days 7, 14, and 30 after MCAO, Tregs and antigen presenting
      cells were analyzed using fluorescence activated cell sorting multicolor staining
      and immunohistochemistry. A strong accumulation of Tregs was observed on days 14
      and 30 in the ischemic hemisphere accompanied by the elevated presence and
      activation of microglia. Dendritic cells and macrophages were found on each
      analyzed day. About 60% of Foxp3(+) Tregs in ischemic hemispheres were positive
      for the proliferation marker Ki-67 on days 7 and 14 after MCAO. The transfer of
      naive CD4(+) cells depleted of Foxp3(+) Tregs into RAG1(-/-) mice 1 day before
      MCAO did not lead to a de novo generation of Tregs 14 days after surgery. After
      depletion of CD25(+) Tregs, no changes regarding neurologic outcome were
      detected. The sustained presence of Tregs in the brain after MCAO indicates a
      long-lasting immunological alteration and involvement of brain cells in
      immunoregulatory mechanisms.

PMID- 22968322
TI  - Glucose modulation of spreading depression susceptibility.
AB  - Spreading depression of Leao is an intense spreading depolarization (SD) wave
      associated with massive transmembrane ionic, water, and neurotransmitter shifts.
      Spreading depolarization underlies migraine aura, and occurs in brain injury,
      making it a potential therapeutic target. While susceptibility to SD can be
      modulated pharmacologically, much less is known about modulation by systemic
      physiological factors, such as the glycemic state. In this study, we
      systematically examined modulation of SD susceptibility by blood glucose in
      anesthetized rats under full physiological monitoring. Hyperglycemia and
      hypoglycemia were induced by insulin or dextrose infusion (blood glucose ~40 and
      400 mg/dL, respectively). Spreading depolarizations were evoked by direct
      cortical electrical stimulation to determine the intensity threshold, or by
      continuous topical KCl application to determine SD frequency. Hyperglycemia
      elevated the electrical SD threshold and reduced the frequency of KCl-induced
      SDs, without significantly affecting other SD properties. In contrast,
      hypoglycemia significantly prolonged individual and cumulative SD durations, but
      did not alter the electrical SD threshold, or SD frequency, amplitude or
      propagation speed. These data show that increased cerebral glucose availability
      makes the tissue resistant to SD.

PMID- 22968323
TI  - Feedback-controlled bolus plus infusion (FC-B/I) method for quantitative drug
      assessment in living brain with PET.
AB  - We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for
      monitoring the interaction between positron emission tomography (PET) ligands and
      their specific target molecules with PET. The usefulness of the FC-B/I method was
      evaluated by the direct interaction between [(11)C]raclopride, a dopamine D(2)
      receptor (D(2)R) ligand, and cold raclopride (10 and 100 MUg/kg) in the brains of
      conscious monkeys. The present results demonstrated that the FC-B/I method could
      achieve the equilibrium state of [(11)C]raclopride in the striatum of monkey
      brain, and also that the cold raclopride-induced reduction of [(11)C]raclopride
      binding to D(2)R was observed in a dose-dependent manner. Good correlations of
      distribution volume ratio of the striatum to cerebellum between the conventional
      bolus plus infusion (B/I) method and the FC-B/I method as well as between the
      conventional bolus injection method and the FC-B/I method were observed. These
      results indicated that the system could be a useful tool for the evaluation of
      interaction between drug candidates and their target molecules like enzymes,
      receptors, and transporters by using of their specific PET ligands.

PMID- 22968324
TI  - Vitamin D status and oxidative stress markers in the elderly with impaired
      fasting glucose and type 2 diabetes mellitus.
AB  - BACKGROUND AND AIMS: Vitamin D deficiency has been identified in the elderly as a
      potential risk factor for cardiovascular disease development, possibly through
      its association with other risk factors, such as type 2 diabetes mellitus (T2DM),
      hypercholesterolemia and hypertension. The aim of this cross-sectional study was
      to evaluate the vitamin D status in elderly subjects with impaired fasting
      glucose (IFG) or T2DM, and to examine its relationships to systemic oxidative
      stress and biochemical markers of endothelial dysfunction. METHODS: Serum 25
      hydroxyvitamin D [25(OH)D], fasting glucose, insulin, lipid profile, advanced
      glycation end products (AGEs), advanced oxidation protein products (AOPPs), low
      density lipoprotein susceptibility to oxidation (oxLDL) and nitric oxide
      metabolic pathway products (NOx) were analyzed in elderly subjects with IFG
      (n=30) and T2DM (n=35) compared with aged-matched controls (n=25). RESULTS:
      25(OH)D levels in the IFG and T2DM groups were significantly lower than in
      controls (31.9+/-1.9 and 28.5+/-1.9 vs 39.4+/-2.4 ng/mL, p<0.001), and associated
      with significantly (p<0.001) higher levels of the oxidative stress parameters
      AGEs, AOPPs, oxLDL and NOx. Hypovitaminosis D [25(OH)D)<30 ng/ml] markedly
      enhanced the oxidative stress and cardiovascular risk in hyperglycemic subjects
      compared with sufficient vitamin D [25(OH)D)>=30 ng/mL] status subjects. In
      subjects with IFG and T2DM (n=65), the vitamin D status was significantly
      inversely correlated both with oxLDL (r=-0.413, p=0.001) and AOPPs (r=-0.475,
      p<0.001), and strongly positively associated with highdensity lipoprotein
      cholesterol (r=0.609, p<0.001). CONCLUSIONS: In the elderly with impaired glucose
      metabolism the vitamin D status is inversely associated with levels of
      circulating markers of oxidative stress and endothelial dysfunction, especially
      in subjects with hypovitaminosis D.

PMID- 22968325
TI  - Improved microbial electrocatalysis with osmium polymer modified electrodes.
AB  - Using the well-known exoelectrogen Shewanella oneidensis MR-1, an osmium redox
      polymer modified anode exhibited ca. 4-fold increase in current generation.
      Additionally, a significant decrease in the start-up time for electrocatalysis
      was observed. The findings suggest that the inherent extracellular electron
      transfer capabilities of electrogens coupled with such polymers could enhance
      electrocatalysis.

PMID- 22968326
TI  - Solvothermal synthesis and characterization of two inorganic-organic hybrid
      materials based on barium.
AB  - Two metal-organic frameworks containing barium were synthesized hydrothermally
      and investigated for their catalytic properties. Ba(2)F(2)[O(3)SC(2)H(4)SO(3)]
      has barium fluoride layers linked by organic 1,2-ethanedisulfonate molecules.
      Ba[O(3)SC(2)H(4)SO(3)] has discrete barium centers arranged in layers and
      connected covalently by ethanedisulfonate bridges. Thermogravimetric analysis
      showed that Ba(2)F(2)[O(3)SC(2)H(4)SO(3)] is stable to ca. 325  degrees C and
      Ba[O(3)SC(2)H(4)SO(3)] to ca. 375  degrees C. These materials expand the metal
      organic frameworks available for group II metals bound to organodisulfonate
      linkers and are potentially useful for a range of heterogeneous acid catalysis
      reactions.

PMID- 22968327
TI  - Arcellacea (testate lobose amoebae) as pH indicators in a pyrite mine-acidified
      lake, Northeastern Ontario, Canada.
AB  - Arcellacea (testate lobose amoebae) were examined in 24 sediment-water interface
      samples collected over two late August field seasons in 2010 and 2011, from James
      and Granite lakes, Temagami Region, Northeastern Ontario. The work was carried
      out to quantitatively test species-environment relationships in a lake system
      known to be characterized by a significant pH gradient, partially the result of
      contamination from the early twentieth century Northland Pyrite Mine Co., located
      on the shoreline in the southern basin of James Lake. Redundancy analysis
      confirmed that arcellacean assemblage structure was most strongly controlled by
      pH, explaining 14.06 % (p < 0.002) of the total variance. Q- and R-mode cluster
      analysis supported by detrended correspondence analysis yielded two major faunal
      assemblages. The Oligotrophic Assemblage (1) had a Shannon Diversity Index (SDI)
      ranging up to 2.45, typical of healthy boreal lakes. This assemblage
      characterized samples collected from higher pH stations within James and Granite
      lakes away from the immediate area of the mine site, while the Low pH Assemblage
      2010 (2a) and Low pH Assemblage 2011 (2b) groupings were from the very low pH
      environments of James Lake adjacent to the former mine site. Both low diversity
      assemblages (SDI ranging from 0.62 to 1.22) were characterized by Arcella
      vulgaris, a species known to thrive in hostile lacustrine environments. Differing
      depositional conditions during August 2010, a probable result of different
      prevailing wind patterns that summer, led to allochthonous specimens of the
      seasonally planktic Cucurbitella tricuspis dominating the Low pH Assemblage 2010
      (2a) fauna.

PMID- 22968328
TI  - Pyrosequencing analysis of the salivary microbiota of healthy Chinese children
      and adults.
AB  - Describing the biogeography of bacterial communities within the human body is
      critical for establishing healthy baselines from which to detect differences
      associated with diseases. Little is known, however, about the baseline of normal
      salivary microbiota from healthy Chinese children and adults. With parallel
      barcoded 454 pyrosequencing, the bacterial diversity and richness of saliva were
      thoroughly investigated from ten healthy Chinese children and adults. The overall
      taxonomic distribution of our metagenomic data demonstrated that the diversity of
      salivary microbiota from children was more complex than adults, while the
      composition and richness of salivary microbiota were similar in children and
      adults, especially for predominant bacteria. A large number of bacterial
      phylotypes were shared by healthy children and adults, indicating the existence
      of a core salivary microbiome. In children and adults, the vast majority of
      sequences in salivary microbiota belonged to Streptococcus, Prevotella,
      Neisseria, Haemophilus, Porphyromonas, Gemella, Rothia, Granulicatella,
      Fusobacterium, Actinomyces, Veillonella, and Aggregatibacter, which constituted
      the major components of normal salivary microbiota. With the exception of
      Actinomyces, the other seven non-predominant bacteria including Moraxella,
      Leptotrichia, Peptostreptococcus, Eubacterium, and members of Neisseriaceae,
      Flavobacteriaceae, and SR1 showed significant differences between children and
      adults (p < 0.05). We first established the framework of normal salivary
      microbiota from healthy Chinese children and adults. Our data represent a
      critical step for determining the diversity of healthy microbiota in Chinese
      children and adults, and our data established a platform for additional large
      scale studies focusing on the interactions between health and diseases in the
      future.

PMID- 22968329
TI  - Aldo Leopold's land health from a resilience point of view: self-renewal capacity
      of social-ecological systems.
AB  - Health approaches to ecology have a strong basis in Aldo Leopold's thinking, and
      contemporary ecohealth in turn has a strong philosophical basis in Leopold. To
      commemorate the 125th anniversary of Leopold's birth (1887-1948), we revisit his
      ideas, specifically the notions of stewardship (land ethic), productive use of
      ecosystems (land), and ecosystem renewal. We focus on Leopold's perspective on
      the self-renewal capacity of the land, as understood in terms of integrity and
      land health, from the contemporary perspective of resilience theory and
      ecological theory more generally. Using a broad range of literature, we explore
      insights and implications of Leopold's work for today's human-environment
      relationships (integrated social-ecological systems), concerns for biodiversity,
      the development of agency with respect to stewardship, and key challenges of his
      time and of ours. Leopold's seminal concept of land health can be seen as a
      triangulation of productive use, self-renewal, and stewardship, and it can be
      reinterpreted through the resilience lens as the health of social-ecological
      systems. In contemporary language, this involves the maintenance of biodiversity
      and ecosystem services, and the ability to exercise agency both for conservation
      and for environmental justice.

PMID- 22968330
TI  - Effects of shear stress on germ lineage specification of embryonic stem cells.
AB  - Mechanobiology to date has focused on differentiated cells or progenitors, yet
      the effects of mechanical forces on early differentiation of pluripotent stem
      cells are still largely unknown. To study the effects of cellular deformation, we
      utilize a fluid flow bioreactor to apply steady laminar shear stress to mouse
      embryonic stem cells (ESCs) cultured on a two dimensional surface. Shear stress
      was found to affect pluripotency, as well as germ specification to the
      mesodermal, endodermal, and ectodermal lineages, as indicated by gene expression
      of OCT4, T-BRACHY, AFP, and NES, respectively. The ectodermal and mesodermal
      response to shear stress was dependent on stress magnitude (ranging from 1.5 to
      15 dynes cm(-2)). Furthermore, increasing the duration from one to four days
      resulted in a sustained increase in T-BRACHY and a marked suppression of AFP.
      These changes in differentiation occurred concurrently with the activation of Wnt
      and estrogen pathways, as determined by PCR arrays for signalling molecules.
      Together these studies show that the mechanical microenvironment may be an
      important regulator during early differentiation events, including gastrulation.
      This insight furthers understanding of normal and pathological events during
      development, as well as facilitates strategies for scale up production of stem
      cells for clinical therapies.

PMID- 22968331
TI  - Assessment of adult formulas for glomerular filtration rate estimation in
      children.
AB  - BACKGROUND: Estimated glomerular filtration rate (eGFR) is an important
      diagnostic instrument in clinical practice. The National Kidney Foundation-Kidney
      Disease Quality Initiative (NKF-KDOQI) guidelines do not recommend using formulas
      developed for adults to estimate GFR in children; however, studies confirming
      these recommendations are scarce. The aim of our study was to evaluate the
      accuracy of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      formula, the Modification of Diet in Renal Disease (MDRD) formula, and the
      Cockcroft-Gault formula in children with various stages of chronic kidney disease
      (CKD). METHODS: A total of 550 inulin clearance (iGFR) measurements for 391
      children were analyzed. The cohort was divided into three groups: group 1, with
      iGFR >90 ml/min/1.73 m(2); group 2, with iGFR between 60 and 90 ml/min/1.73 m(2);
      group 3, with iGFR of <60 ml/min/1.73 m(2). RESULTS: All formulas overestimate
      iGFR with a significant bias (p < 0.001), present poor accuracies, and have poor
      Spearman correlations. For an accuracy of 10 %, only 11, 6, and 27 % of the eGFRs
      are accurate when using the MDRD, CKD-EPI, and Cockcroft-Gault formulas,
      respectively. For an accuracy of 30 %, these formulas do not reach the NKF-KDOQI
      guidelines for validation, with only 25, 20, and 70 % of the eGFRs, respectively,
      being accurate. CONCLUSIONS: Based on our results, the performances of all of
      these formulas are unreliable for eGFR in children across all CKD stages and
      cannot therefore be applied in the pediatric population group.

PMID- 22968333
TI  - Nanowires as semi-rigid substrates for growth of thick, In(x)Ga(1-x)N (x > 0.4)
      epi-layers without phase segregation for photoelectrochemical water splitting.
AB  - Here, we show that GaN nanowires (diameter <30 nm) can be used as strain relaxing
      substrates for the heteroepitaxial growth of stable In(x)Ga(1-x)N alloys of
      controlled composition and thickness. Thinner nanowires with their smaller
      interfacial area reduce the heteroepitaxial stress. Also, the limited adatom
      diffusion length scales on the thinner nanowires aid in reducing the kinetic
      segregation effects. In addition to being single crystal templates for
      heteroepitaxial growth, these thick single crystal overlayers on nanowire
      substrates can provide suitable architectures for photoelectrochemical
      applications. The stability and crystallinity of the In(x)Ga(1-x)N layers are
      preserved by the nanowires acting as compliant substrates. Photoelectrochemical
      water splitting requires In(x)Ga(1-x)N alloys with a 2.2-1.6 eV band gap (i.e.
      0.45 < x < 0.65) and 150-200 nm film thickness for efficient light absorption and
      carrier generation. At such compositions, the In(x)Ga(1-x)N alloys are inherently
      unstable, the thickness-dependent stress builds up during the commonly employed
      heteroepitaxial growth methods, and adds to the instability causing phase
      segregation and property degradation. A dependence of the growth morphology on
      the GaN nanowire growth orientation was observed and a growth mechanism is
      presented for the observed orientation dependent growth on a-plane and c-plane
      GaN nanowires. Photoactivity of GaN and In(x)Ga(1-x)N films on GaN nanowires is
      also investigated which shows a distinct difference attributable to GaN and
      In(x)Ga(1-x)N, demonstrating the advantages of using nanowires as strain relaxing
      substrates.

PMID- 22968332
TI  - Sleep disturbance and depressive symptoms in adolescence: the role of
      catastrophic worry.
AB  - Depression is a common and debilitating disorder in adolescence. Sleep
      disturbances and depression often co-occur with sleep disturbances frequently
      preceding depression. The current study investigated whether catastrophic worry,
      a potential cognitive vulnerability, mediates the relationship between adolescent
      sleep disturbances and depressive symptoms, as well as whether there are gender
      differences in this relationship. High school students, ages 16-18, n = 1,760,
      49% girls, completed annual health surveys including reports of sleep
      disturbance, catastrophic worry, and depressive symptoms. Sleep disturbances
      predicted depressive symptoms 1-year later. Catastrophic worry partially mediated
      the relationship. Girls reported more sleep disturbances, depressive symptoms,
      and catastrophic worry relative to boys. The results, however, were similar
      regardless of gender. Sleep disturbances and catastrophic worry may provide
      school nurses, psychologists, teachers, and parents with non-gender specific
      early indicators of risk for depression. Several potentially important practical
      implications, including suggestions for intervention and prevention programs, are
      highlighted.

PMID- 22968334
TI  - Molecular and cellular mechanisms of macrophage survival in atherosclerosis.
AB  - Macrophages play a key role in the initiation and progression of atherosclerotic
      plaques. Although a significant number of macrophages undergoes cell death during
      plaque development as a result of atherogenic stressors, advanced plaques are
      characterized by a large macrophage content. Macrophage accumulation is mediated
      by continuous recruitment of monocytes, reduced emigration of macrophages and
      poor phagocytosis of dead cells which may trigger secondary necrosis and
      amplification of plaque inflammation. Moreover, an increasing body of evidence
      indicates that macrophages have developed several strategies to survive and to
      proliferate in the adverse environment of an advanced atherosclerotic plaque.
      Macrophages contain organic molecules or enzymes that provide enhanced
      antioxidant protection. In addition, synthesis of anti-apoptotic proteins is
      upregulated and several cellular protection mechanisms such as the unfolded
      protein response and autophagy are activated in macrophages to promote cellular
      survival. In this review, we discuss these macrophage survival mechanisms that
      allow growth and destabilization of advanced atherosclerotic plaques.

PMID- 22968335
TI  - Estimation of dietary intake and patterns of polyphenol consumption in Polish
      adult population.
AB  - PURPOSE: Polyphenols play an important role in the prevention of degenerative
      diseases, particularly cardiovascular diseases and cancers. The purpose was to
      estimate dietary polyphenol intake in Polish adults, using own database of food
      polyphenols, and to establish main dietary sources of polyphenols. MATERIAL AND
      METHODS: Polish men and women (6661) aged 20-74 years were randomly selected from
      the Polish National Multicenter Health Survey (WOBASZ). Subjects' daily food
      consumption was estimated by the 24-hour recall method and was continued for 3
      years. It was determined on this basis, that 96 plant foods and plant food
      products were consumed. The own dietary database of polyphenol contents in food
      was used to calculate polyphenol intakes in the subjects. The daily total
      polyphenol intakes were calculated for both genders in individual age categories:
      20-40 years, 41-60 years and 61-74 years. RESULTS: The average polyphenol
      consumption for the men was 1172 mg/day, and for the women it made 1031 mg/day.
      Plant food categories such as beverages, vegetables, fruits and cereals were
      found to be significant sources of polyphenols, of which tea, coffee, potatoes,
      apples and white bread were the main contributors. CONCLUSIONS: The amount of
      polyphenol consumption in Polish adult population is similar to the polyphenol
      intake in other countries populations, accounting roughly for 1g of polyphenols
      for both genders and different age groups. Patterns of polyphenol consumption,
      however, vary for genders and age groups. Polyphenols are characterized by a
      spectrum of antioxidant capabilities, therefore future studies should focus on
      dietary intakes of individual polyphenols.

PMID- 22968336
TI  - Pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients
      after the first intravenous administration of 400 mg.
AB  - PURPOSE: To investigate the pharmacokinetics and pharmacodynamics of
      ciprofloxacin in critically ill patients after the first intravenous
      administration of 400 mg. MATERIAL/METHODS: Plasma concentrations were measured
      in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3
      [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples
      were drawn at the following time points 0, 0.5, 6 , 8 hours after infusion.
      Ciprofloxacin concentrations were determined by high-performance liquid
      chromatography. RESULTS: In the cases where ciprofloxacin was applied in targeted
      antibiotic therapy the minimum inhibitory concentrations (MIC) were <=0.5 mg/l.
      The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58
      7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic
      parameters for ciprofloxacin in the analyzed patients were as follows: k(el),
      0.21 h-1; t(1/2kel), 3.37 h; AUC(0-inf), 10.10 mg*h/l; AUMC(0-last), 15.36
      mg*h(2)/l; MRT, 1.71 h; V(d), 214.8 l; Cl, 39.70 l/h. Considering the maximum
      value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values
      of the PK/PD indexes AUIC>125 and C(max) /MIC>10, respectively. CONCLUSIONS: The
      target plasma concentrations after the first dose of ciprofloxacin were reached
      only in a few critically ill patients. Considerable inter-subject variability for
      PK/PD parameters in ICU patients requires systematic monitoring.

PMID- 22968337
TI  - Diversity of Babesia in Ixodes ricinus ticks in Poland.
AB  - PURPOSE: The aims of this study were: (1) to estimate Babesia prevalence in the
      most common species of tick in Poland, Ixodes ricinus, in two recreational areas
      (Urwitalt in the Mazury Lake District and Bielanski Forest in Warsaw), and (2) to
      evaluate the molecular diversity of Babesia isolates in questing I. ricinus in
      Poland. MATERIAL AND METHODS: Questing ticks were collected from vegetation in
      forest areas in Urwitalt near Mikolajki and in Bielanski Forest (Warsaw).
      Purified genomic DNA was used with specific primers to amplify a fragment of the
      Babesia spp. 18S rRNA gene. RESULTS: Tick-drag indices for I. ricinus were high
      in both study areas, reaching somewhat higher values in Urwitalt than in
      Bielanski Forest. The overall prevalence of Babesia spp. in examined ticks was
      1.6%. In Urwitalt, two strains of B. microti were identified using rRNA
      sequences: the enzootic Munich strain and an isolate close to the zoonotic Jena
      strain. The proportion of infections due to these two strains in questing ticks
      reversed over a six-year period. During 3 years of study in Bielanski Forest, all
      Babesia isolates obtained from I. ricinus were identical to Babesia sp. EU1 (B.
      venatorum), previously recognized as an agent of human babesiosis. CONCLUSIONS:
      This study has confirmed the presence of enzoonotic and zoonotic Babesia
      species/strains in the abundant human-biting tick I. ricinus in recreational
      areas in Poland. It has also shown that the distribution of different genotypes
      has changed over time, however the reasons for these fluctuations still remain to
      be investigated.

PMID- 22968338
TI  - Mast cells and eosinophils are involved in activation of ulcerative colitis.
AB  - PURPOSE: The intestinal mucosal immune cells such as the mast cells and
      eosinophils play an important role in the pathogenesis of ulcerative colitis
      (UC). The aim of present study was to compare the number of mast cells and
      eosinophils in patients with active and non-active ulcerative colitis. Another
      purpose was to found whether the number of eosinophils could correlate with
      number of mast cells in both tested groups. MATERIAL AND METHODS: The twenty-five
      of formalin-fixed, paraffin-embedded tissue specimens of active ulcerative
      colitis, the twenty of non-active ulcerative colitis and the ten of controls were
      retrieved from archival material. Tryptase and chymase immunopositive cells were
      detected using immunohistochemical method. Additionally, the number of mast cells
      and eosinophils were detected using the most common histochemical methods.
      RESULTS: The number of eosinophils and toluidine blue stained and tryptase
      immunopositive mast cells was significantly increased in active UC compared to
      non-active UC. In active stage of UC positive correlation between the number of
      mast cells stained with toluidine blue and the number of chymase and tryptase
      immunopositive mast cells were observed. Moreover, the number of eosinophils was
      significantly correlated with number of mast cells stained with toluidine blue
      and number of tryptase- and chymase immunopositive mast cells. In non-active
      stage of UC positive correlation was observed only between the number of mast
      cells stained with toluidine blue and chymase immunopositive cells and
      eosinophils. CONCLUSIONS: In conclusion, our findings confirmed that mast cells
      and eosinophils are functionally involved in the course of UC.

PMID- 22968339
TI  - Probiotic-induced apoptosis and its potential relevance to mucosal inflammation
      of gastrointestinal tract.
AB  - In this short review we attempt to establish and/or strengthen connections
      between probiotics administration and apoptotic pathway in gastrointestinal
      tract. The disturbance of apoptosis is mainly deliberated in the framework of
      insufficient removal of immuno-effector cells that may cause autoimmunity. In the
      context of the inflammatory bowel disease (IBD) and necrotizing enterocolitis
      (NEC), the commensal bacteria and their products effect on gut and immune cell
      survival are illustrated. The multitude of mechanisms of probiotics to induce
      cell death is shortly summarized and some aspects of it are being discussed in
      greater detail. The mechanism of intestinal cell death induced by probiotic
      administration and its influence on the immune system and potential benefits of
      apoptosis induction during probiotic therapy is indicated.

PMID- 22968341
TI  - The usefulness of glycated hemoglobin A1c (HbA1c) for identifying dysglycemic
      states in individuals without previously diagnosed diabetes.
AB  - PURPOSE: We investigated HbA1c's validity as a screening parameter for excluding
      dysglycemic states in the studied population. MATERIAL/METHODS: Sensitivity and
      specificity of HbA1c in some cut-off points were compared with diagnoses based on
      the oral glucose tolerance test (OGTT) in individuals diagnosed between 2009
      2010. Receiver operating characteristic (ROC) analysis for HbA1c was conducted.
      HbA1c and OGGT measures were done in 441 people (253 women, 187 men, average age
      40.1 years (18-79 years)). Based on the OGGT test 37 individuals were diagnosed
      as diabetic, 28 as impaired glucose tolerant (IGT) and 63 as having impaired
      fasting glycemia (IFG). RESULTS: A cut-off value of 6.5% HbA1c classifies
      diabetic subjects with a sensitivity of 45.9% and specificity of 97.5%. In the
      investigated population the best cut-off point (the highest sum of the
      sensitivity and specificity) was 5.9% HbA1c (sensitivity 86.6%, specificity 73%).
      HbA1c values excluding the risk of dysglycemic states have shown false negative
      rate in 31.9% when HbA1c was 5.5% and 10.6% when HbA1c was 5.0%. CONCLUSIONS: Our
      results indicate that in the investigated population the evaluation of the
      prevalence of type 2 diabetes using HbA1c values proposed by the American
      Diabetes Association (ADA) has unsatisfactory sensitivity and detects less than a
      half of cases of diabetes based on the OGTT diagnoses. HbA1c 5.7% does not have
      sufficient specificity to identify individuals not being at risk of any disorder
      of glucose metabolism.

PMID- 22968340
TI  - Variability of hepatitis C virus hypervariable region 1 (HVR-1) during the early
      phase of pegylated interferon and ribavirin therapy.
AB  - PURPOSE: Genetic variability of hepatitis C virus (HCV) is considered to be an
      important factor defining viral pathogenesis, persistence and resistance to
      treatment. The aim of the present study was to characterize HCV genetic
      heterogeneity within a hypervariable region 1 (HVR-1) before and during the early
      period of pegylated interferon alfa (PEG-IFN-alpha) and ribavirin treatment in
      correlation with treatment outcome. MATERIAL AND METHODS: The study involved 24
      patients treated with PEG-IFN-alpha and ribavirin whose sera were collected
      before (baseline) and at 7, 14, 21 28 and 56 day of treatment. HCV HVR-1 region
      was amplified by nested RT- PCR and subjected to SSCP (single strand
      conformational polymorphism) analysis. SSCP changes of HCV HVR-1 over time in
      each patient were compared to treatment outcome results. RESULTS: In 2/11 (18%)
      SVR+ and 8/13 (62%) SVR- treated patients, HVR-1 genetic changes manifested by
      new SSCP bands (new genetic variants) and were significantly more frequent in
      nonresponders (P <0.05). CONCLUSIONS: Our results indicate that HCV HVR-1
      variability during the early phase of PEG-IFN-alpha and ribavirin therapy may be
      predictive of treatment outcome.

PMID- 22968343
TI  - Cyclin-dependent kinase 5 immunoreactivity for granulovacuolar degeneration.
AB  - In addition to senile plaque and neurofibrillary tangles, granulovacuolar
      degeneration is a hallmark of Alzheimer's disease. A number of tau kinases, such
      as c-jun N-terminal kinase (JNK), glycogen-synthase kinase-3beta (GSK3beta), and
      casein kinase 1 (CK1), have been reported to be markers of granulovacuolar
      degeneration. In addition, cyclin-dependent kinase 5 (CDK5), which phosphorylates
      tau, has been shown to be abundantly expressed in neurofibrillary tangles in the
      hippocampus. CDK5 has a unique staining pattern, and therefore, has the potential
      to be a novel marker for granulovacuolar degeneration. In this study, we
      investigated the ability of CDK5 to be a marker for granulovacuolar degeneration
      using immunohistochemical analysis. Four Alzheimer's disease cases, three
      myotonic dystrophy (MyD) cases, and three control cases were subjected to
      immunohistochemistry and immunofluorescent techniques using anti-CDK5, anti
      charged multivesicular body protein 2B (CHMP2B), anti-pSmad2/3, anti-ubiquitin
      (Ub), anti-phospho-TDP-43 and AT8 antibodies. Some CDK5-positive granules were
      morphologically similar to granulovacuolar degeneration intraluminal granules,
      and these granules overlapped with those immunopositive for pSmad2/3, Ub and
      phospho-TDP-43 established granulovacuolar degeneration markers. Moreover, CDK5
      positive granulovacuolar degeneration and phosphorylated tau colocalized in
      pyramidal neurons in Alzheimer's disease and MyD cases. The numbers of CDK5
      positive granules showed an inverse relationship with the degree of mature
      neurofibrillary tangles in each cell, as was the case with CHMP2B-positive
      granulovacuolar degeneration granules and neurofibrillary tangles. The presence
      of tau kinases including CDK5 in granulovacuolar degeneration might implicate
      that granulovacuolar degeneration is structurally involved in tau modification.

PMID- 22968345
TI  - Dietary lysine requirement of fingerling Catla catla (Hamilton) based on growth,
      protein deposition, lysine retention efficiency, RNA/DNA ratio and carcass
      composition.
AB  - A 12-week experiment was conducted to quantify dietary lysine requirement of
      fingerling Catla catla (3.65 +/- 0.05 cm; 0.58 +/- 0.02 g) by feeding casein
      gelatine-based diets (33.0 % crude protein; 14.3 kJ/g digestible energy) with six
      levels of L-lysine (1.25, 1.50, 1.75, 2.00, 2.25 and 2.50 % dry diet). The
      experiment was conducted in eighteen 70-L indoor polyvinyl circular troughs
      provided with a water flow-through system (1-1.5 L/min). Live weight gain (LWG),
      feed conversion ratio (FCR), protein deposition (PD), lysine retention efficiency
      (LRE%) and RNA/DNA ratio were used as the response criteria. Second-degree
      polynomial regression analysis at 95 % maximum and minimum response of LWG and
      FCR data exhibited the lysine requirement between 1.8 and 1.9 % dry diet,
      corresponding to 5.5-5.7 % dietary protein. Regression analysis of PD, LRE and
      RNA/DNA ratio yielded the requirement between 1.7 and 1.8 % dry diet,
      corresponding to 5.2-5.5 % dietary protein. Since live weight gain and protein
      deposition are the key parameters for estimating nutrient requirement, these
      tools were used to recommend the lysine requirement of fingerling C. catla which
      ranges between 1.7 and 1.8 % dry diet. Data generated during this study will be
      useful to formulate lysine-balanced feed for intensive culture of this fish.

PMID- 22968346
TI  - The role of hydroxylation in the step stability and in the interaction between
      steps: a first-principles study of vicinal MgO surfaces.
AB  - Atomic structure and thermodynamic stability of vicinal MgO surfaces showing
      monoatomic steps are studied using density functional theory. We extend the
      general definition of step energy to the case of ledges that are covered by
      adsorbates. Using this definition, we consider the effect of hydroxylation on the
      thermodynamic stability of steps, either polar or non-polar, on (001) or (011)
      terraces. Clean non-polar steps along [100] on MgO(001) are the most stable ones.
      Upon water adsorption, the free energy of all hydroxylated ledges, almost
      independently of their orientation, is significantly reduced and approaches
      thermal energies for increasing water pressure, favoring the formation of
      hydroxylated steps on MgO surfaces. Furthermore, we show that interaction between
      polar steps can be either repulsive or attractive. This quite unusual behavior is
      described in terms of electrostatic interactions between ledges.

PMID- 22968342
TI  - Multiple functions of tristetraprolin/TIS11 RNA-binding proteins in the
      regulation of mRNA biogenesis and degradation.
AB  - Members of the tristetraprolin (TTP/TIS11) family are important RNA-binding
      proteins initially characterized as mediators of mRNA degradation. They act via
      their interaction with AU-rich elements present in the 3'UTR of regulated
      transcripts. However, it is progressively appearing that the different steps of
      mRNA processing and fate including transcription, splicing, polyadenylation,
      translation, and degradation are coordinately regulated by multifunctional
      integrator proteins that possess a larger panel of functions than originally
      anticipated. Tristetraprolin and related proteins are very good examples of such
      integrators. This review gathers the present knowledge on the functions of this
      family of RNA-binding proteins, including their role in AU-rich element-mediated
      mRNA decay and focuses on recent advances that support the concept of their
      broader involvement in distinct steps of mRNA biogenesis and degradation.

PMID- 22968344
TI  - The dementia of cardiac disease.
AB  - Cardiovascular disease and dementia are common in the elderly and are major
      causes of disability in the general population. The public health burden of
      dementia is projected to increase as life expectancy increases in the United
      States and elsewhere. Epidemiological studies suggest that these once believed
      unrelated conditions, heart disease and dementia, may be linked by shared common
      risks and pathogenic elements. These observations have sparked the notion that
      prevention or modification of certain vascular risk factors and proper management
      of cardiovascular disease may prevent the development or progression of dementia
      including Alzheimer's disease. In this article, the authors discuss the
      association between cognitive impairment and atrial fibrillation, coronary artery
      disease, congestive heart failure, and cardiovascular procedures.

PMID- 22968347
TI  - Complications related to femoral artery access for transcatheter procedures.
AB  - Percutaneous-based procedures continue to increase as endovascular techniques
      improve and provide a less morbid approach than the open vascular procedures. The
      most common complications associated with either cardiac interventions or
      peripheral interventions involve the access point of the procedure. The
      retrograde femoral access has and is currently the most frequently used arterial
      access. Vascular surgeons have been responsible for management of complications
      following femoral-based procedures and now are a significant contributor to
      catheter-based diagnostic and interventional procedures. This review provides in
      depth review of the literature on specific complications encountered during
      percutaneous femoral artery puncture. This review includes access complications
      related to the method of obtaining access (ie, best pulse fluoroscopic guided),
      direction of access either retrograde or antegrade, risk factors and incidence of
      complications based on best literature sources, and management strategies for
      specific complications.

PMID- 22968348
TI  - Exposure to cooking oil fumes and oxidative damages: a longitudinal study in
      Chinese military cooks.
AB  - Cooking oil fumes (COF) contain polycyclic aromatic hydrocarbons (PAHs),
      heterocyclic aromatic amines, benzene, and formaldehyde, which may cause
      oxidative damages to DNA and lipids. We assessed the relations between exposure
      to COF and subsequent oxidative DNA damage and lipid peroxidation among military
      cooks and office-based soldiers. The study population, including 61 Taiwanese
      male military cooks and a reference group of 37 office soldiers, collected urine
      samples pre-shift of the first weekday and post-shift of the fifth workday. We
      measured airborne particulate PAHs in military kitchens and offices and
      concentrations of urinary 1-OHP, a biomarker of PAH exposure, urinary 8
      hydroxydeoxyguanosine (8-OHdG), a biomarkers of oxidative DNA damage, and urinary
      isoprostane (Isop). Airborne particulate PAHs levels in kitchens significantly
      exceeded those in office areas. The concentrations of urinary 1-OHP among
      military cooks increased significantly after 5 days of exposure to COF. Using
      generalized estimating equation analysis adjusting for confounding, a change in
      log(8-OHdG) and log(Isop) were statistically significantly related to a unit
      change in log(1-OHP) (regression coefficient (beta), beta=0.06, 95% CI 0.001
      0.12) and (beta=0.07, 95% CI 0.001-0.13), respectively. Exposure to PAHs, or
      other compounds in cooking oil fumes, may cause both oxidative DNA damage and
      lipid peroxidation.

PMID- 22968350
TI  - Evaluation of individual-based and group-based exposure estimation of microbial
      agents in health effects associated with a damp building.
AB  - We evaluated attenuation in linear associations between microbial exposure and
      respiratory symptoms occurring when individual measurements of microbial agents
      were used for estimating employees' exposure compared with group means. Symptoms,
      which improved when away from the building (building-related, BR), and
      measurements of culturable fungi, ergosterol, and endotoxin in floor dust were
      obtained between 2001 and 2007 from four cross-sectional studies on occupants of
      a water-damaged building. We compared odds ratios from longitudinal health effect
      models using individual measurements at employees' workstations with those using
      floor (group) means. Estimated odds for BR respiratory symptoms in group-based
      analyses increased by 2 to 5 times compared with those from individual-based
      analyses for culturable fungi and ergosterol, although they were less precise.
      For endotoxin, we found substantially increased and significant odds in group
      based analyses, while we found no associations in individual-based analyses for
      various symptoms. Our study suggested that the building floor was useful in
      constructing exposure groups for microbial agents in this water-damaged building
      for epidemiologic analysis. Our study showed that group-average exposure
      estimation provides less attenuated associations between exposures to microbial
      agents and health in damp indoor environments where measurement error and
      intrinsic temporal variability are often large.

PMID- 22968349
TI  - Thyroid hormones and thyroid disease in relation to perchlorate dose and
      residence near a superfund site.
AB  - Perchlorate is a widely occurring contaminant, which can competitively inhibit
      iodide uptake and thus thyroid hormone production. The health effects of chronic
      low dose perchlorate exposure are largely unknown. In a community-based study, we
      compared thyroid function and disease in women with differing likelihoods of
      prior and current perchlorate exposure. Residential blocks were randomly selected
      from areas: (1) with potential perchlorate exposure via drinking water; (2) with
      potential exposure to environmental contaminants; and (3) neighboring but without
      such exposures. Eligibility included having lived in the area for >=6 months and
      aged 20-50 years during 1988-1996 (during documented drinking water well
      contamination). We interviewed 814 women and collected blood samples (assayed for
      thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily
      urine samples were assayed for perchlorate and iodide for 178 premenopausal women
      with blood samples. We performed multivariable regression analyses comparing
      thyroid function and disease by residential area and by urinary perchlorate dose
      adjusted for urinary iodide levels. Residential location and current perchlorate
      dose were not associated with thyroid function or disease. No persistent effect
      of perchlorate on thyroid function or disease was found several years after
      contaminated wells were capped.

PMID- 22968351
TI  - Accounting for the impact of short-term variations in the levels of
      trihalomethane in drinking water on exposure assessment for epidemiological
      purposes. Part II: biological aspects.
AB  - The variability of trihalomethane (THM) levels in drinking water raises the
      question of whether or not short-term variations (within-day) should be accounted
      for when assessing exposure to contaminants suspected of being carcinogenic and
      reprotoxic agents. The purpose of this study was to determine the magnitude of
      the impact on predicted biological levels of THMs (internal doses) exerted by
      within-day variations of THMs in drinking water. A database extracted from a
      campaign in the Quebec City distribution system served to produce 81, 79 and 64
      concentration profiles for the three most abundant THMs, namely chloroform (TCM),
      dichlorobromomethane (DCBM) and chlorodibromomethane (CDBM), respectively. Using
      a physiologically based toxicokinetic modeling approach, we simulated exposures
      (1.5 l water per day and a 10-min shower) based on each of these profiles and
      predicted, for 2000 individuals (Monte-Carlo simulations), maximum blood
      concentrations (Cmax), areas under the time versus blood concentrations curve (24
      h-AUCcv) and total absorbed doses (ADs). Three different hypotheses were tested:
      [A] assuming a constant THM concentration in water (e.g., mean value of a day);
      [B] accounting for within-day variations in THM levels; and [C] a worst-case
      scenario assuming within-day variations and showering while THM levels were
      maximal. For each exposure profile, exposure indicator and individual, we
      calculated the ratios of values obtained according to each hypothesis (e.g.,
      CmaxB/CmaxA and CmaxC/CmaxA) and the values corresponding to the 5th and 95th
      percentiles of these ratios. The closer these percentiles are to the value of 1,
      the smaller the error associated with assuming constant THM concentrations rather
      than their actual variability. Results showed that the minimal gap between these
      percentiles was TCM-AD(B)/TCM-AD(A) (5th=0.91; 95th=1.09), whereas the maximal
      gap was CDBM-Cmax(C)/CDBM-Cmax(A) (5th=0.50; 95th=3.40). Overall, TCM and ADs
      were the less affected (TCM<DCBM<CDBM and AD<AUCcv<Cmax) when accounting for
      within-day variations in water levels.

PMID- 22968352
TI  - Cardiac abnormalities in HIV-positive patients: results from an observational
      study in India.
AB  - BACKGROUND: The clinical presentation of cardiac abnormalities in HIV-infected
      patients may be atypical or masked by concurrent illnesses that lead to
      misdiagnosis or they remain undiagnosed; therefore, this study was aimed to
      determine the frequency of cardiac abnormalities in HIV-infected patients.
      MATERIAL AND METHODS: Consecutive HIV-infected patients of age >13 years were
      studied for 3 months, after obtaining their consent. After clinical assessment,
      chest x-ray, electrocardiogram, 2-dimensional echocardiography and serum Troponin
      T levels were done. RESULTS: A total of 100 patients were studied, cardiomegaly
      was observed in the x-ray of 15% of them, abnormal electrocardiogram was seen in
      18%, 2-dimensional echocardiography was abnormal in 67%; and diastolic
      dysfunction (42.8%) was the commonest abnormality followed by dilated
      cardiomyopathy (17.6%). Serum troponin T was elevated in 8%. The variables,
      opportunistic infections (OIs), antiretroviral therapy (ART), stage of HIV
      disease, and CD4 counts, did not affect the frequency of diastolic dysfunction.
      CONCLUSION: The diastolic dysfunction is the most common cardiac abnormality
      observed in HIV-infected patients.

PMID- 22968353
TI  - Development and field testing of an HIV medication touch screen computer patient
      adherence tool with telephone-based, targeted adherence counseling.
AB  - BACKGROUND: HIV medication nonadherence is a major problem, yet many providers
      lack the time and training to carefully ask patients about their adherence.
      OBJECTIVE: To design and pilot a technology-assisted intervention, for use in
      clinical settings, to identify nonadherent patients. METHODS: The intervention
      uses audio computer-assisted self-interview (ACASI) to improve the assessment of
      adherence and medication-related problems. Patients completed a touch screen
      computer ACASI which generated graphic clinician and patient reports for
      discussion during the clinical encounter. RESULTS: 72 patients and 11 providers
      participated in this study. The patients easily completed the ACASI. Adherence
      was 63% (3-day) and 47% (30-day). Using the ACASI, 22% of patients identified
      themselves as nonadherent, when their providers perceived them as adherent.
      CONCLUSIONS: This ACASI-based intervention is easy to use and helps identify
      nonadherence. The pilot test engendered enhancements including the addition of
      phone-based adherence counseling. A larger trial is underway to evaluate whether
      the intervention leads to improved HIV-related outcomes.

PMID- 22968354
TI  - Prolongation of electrode lifetime in biofuel cells by periodic enzyme renewal.
AB  - Enzymatically catalyzed biofuel cells show unique specificity and promise high
      power densities, but suffer from a limited lifetime due to enzyme deactivation.
      In the present work, we demonstrate a novel concept to extend the lifetime of a
      laccase-catalyzed oxygen reduction cathode in which we decouple the electrode
      lifetime from the limited enzyme lifetime by a regular resupply of fresh enzymes.
      Thereto, the adsorption behavior of laccase from Trametes versicolor to
      buckypaper electrode material, as well as its time-dependent deactivation
      characteristics, has been investigated. Laccase shows a Langmuir-type adsorption
      to the carbon nanotube-based buckypaper electrodes, with a mean residence time of
      2 days per molecule. In a citrate buffer of pH 5, laccase does not show any
      deactivation at room temperature for 2 days and exhibits a half-life of 9 days.
      In a long-term experiment, the laccase electrodes were operated at a constant
      galvanostatic load. The laccase-containing catholyte was periodically exchanged
      against a freshly prepared one every second day to provide sufficient active
      enzymes in the catholyte for the replacement of desorbed inactive enzymes.
      Compared to a corresponding control experiment without catholyte exchange, this
      procedure resulted in a 2.5 times longer cathode lifetime of 19 +/- 9 days in
      which the electrode showed a potential above 0.744 V vs. normal hydrogen
      electrode at 110 MUA cm(-2). This clearly indicates the successful exchange of
      molecules by desorption and re-adsorption and is a first step toward the
      realization of a self-regenerating enzymatic biofuel cell in which enzyme
      producing microorganisms are integrated into the electrode to continuously
      resupply fresh enzymes.

PMID- 22968355
TI  - Do low preoperative vitamin D levels reduce the accuracy of quick parathyroid
      hormone in predicting postthyroidectomy hypocalcemia?
AB  - BACKGROUND: Although some studies have suggested that low preoperative 25
      hydroxyvitamin D (25-OHD) levels may increase the risk of hypocalcemia and
      decrease the accuracy of single quick parathyroid hormone in predicting
      hypocalcemia after total thyroidectomy, the literature remains scarce and
      inconsistent. Our study aimed to address these issues. METHODS: Of the 281
      consecutive patients who underwent a total/completion total thyroidectomy, 244
      (86.8%) did not require any oral calcium and/or calcitriol supplements (group 1),
      while 37 (13.2%) did (group 2) at hospital discharge. 25-OHD level was checked 1
      day before surgery, and postoperative quick parathyroid hormone (PTH) was checked
      at skin closure (PTH-SC). Postoperative serum calcium was checked regularly.
      Hypocalcemia was defined by the presence of symptoms or adjusted calcium of <1.90
      mmol/L. Significant factors for hypocalcemia were determined by univariate and
      multivariate analyses. The accuracy of PTH-SC in predicting hypocalcemia was
      measured by area under a receiver operating characteristic curve (AUC), and the
      AUC of PTH-SC was compared between patients with preoperative 25-OHD <15 and >=15
      ng/mL via bootstrapping. RESULTS: Preoperative 25-OHD level was not significantly
      different between groups 1 and 2 (13.1 vs. 12.5 ng/mL, p = 0.175). After
      adjusting for other significant factors, PTH-SC (odds ratio 2.49, 95% confidence
      interval 1.52-4.07, p < 0.001) and parathyroid autotransplantation (odds ratio
      3.23, 95% confidence interval 1.22-8.60, p = 0.019) were the two independent
      factors for hypocalcemia. The AUC of PTH-SC was similar between those with 25-OHD
      <15 and >=15 ng/mL (0.880 vs. 0.850, p = 0.61) CONCLUSIONS: Low 25-OHD was not a
      significant factor for hypocalcemia and did not lower the accuracy of quick PTH
      in predicting postthyroidectomy hypocalcemia.

PMID- 22968356
TI  - A study of host corneal endothelial cells after non-Descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To determine the short-term fate of the host endothelium and Descemet
      membrane after non-Descemet stripping automated endothelial keratoplasty
      (nDSAEK). METHODS: Eight unilateral DSAEK (n = 4) or nDSAEK (n = 4) surgeries
      were performed in the right eyes of 8 rabbits. Corneal transparency and thickness
      were followed-up by slit-lamp microscopy, and 2 weeks postoperatively, corneas
      were evaluated by immunohistochemistry and transmission electron microscopy.
      RESULTS: Corneas remained clear after both DSAEK and nDSAEK. One week after
      DSAEK, the stroma-to-stroma surgical interface was identifiable as a zone of
      fibrotic tissue a few microns thick, whereas in the nDSAEK group, the recipient
      corneal endothelium and Descemet membrane were clearly visible at the graft-host
      interface. The retained endothelial cells were positive for Na/K-ATPase but
      assumed a markedly different morphology from healthy endothelial cells, with cell
      processes extending into the graft stroma or engulfing strands of irregularly
      dissected grafted stromal tissue where they occasionally appeared to
      compartmentalize the transplanted matrix and became detached from the underlying
      Descemet membrane. CONCLUSIONS: Host endothelial cells 2 weeks after nDSAEK
      express markers of pump function, but appear to be morphologically altered,
      occasionally detaching from the adjacent Descemet membrane, extending into the
      graft stroma or engulfing strands of the grafted stroma at the interface. The
      short-term persistence and subsequent phenotypical alternation of residual
      endothelial cells, aligned to structural changes to Descemet membrane, might
      influence graft adherence after nDSAEK.

PMID- 22968357
TI  - Removal of lymphangiectasis using high-frequency radio wave electrosurgery.
AB  - PURPOSE: To describe a novel technique using high-frequency radio wave
      electrosurgery (Ellman Surgitron Dual Frequency RF; Ellman International, Inc)
      for the management of lymphangiectasis. METHODS: Ablations were performed at the
      lowest power setting of 1 (of 100) in the cutting mode, producing the least
      amount of lateral heat. To prevent conjunctival hemorrhage, ablation was
      initiated immediately before introducing the tip of a needle electrode into the
      subconjunctival tissue under the target area. After the tip of the electrode
      reached the target area, ablation was maintained for 1 to 2 seconds on the
      surrounding area and for a longer time on the dilated lymphatic vessels, until
      the target conjunctiva blanched. These ablations were performed cautiously with
      the fine electrode to avoid thermal injury to the adjacent scleral tissue.
      RESULTS: Persistent lymphangiectasis accompanied by accumulated fluid was
      successively treated with high-frequency radio wave electrosurgery. Surgical time
      was less than 5 minutes. There were no intraoperative complications. Fourier
      domain optical coherence tomography revealed resolution of the accumulated fluid
      and a decrease of dilated lymphatic vessels. Postoperatively, no notable
      complications, such as charring, scarring of Tenon capsule, or symblepharon
      resulting from excessive cauterization, were observed. CONCLUSION: High-frequency
      radio wave electrosurgery may be a safe, quick, and effective modality for the
      treatment of symptomatic lymphangiectasis patients.

PMID- 22968358
TI  - Cytostatic and cytotoxic effects of 5-fluorouracil on human corneal epithelial
      cells and keratocytes.
AB  - PURPOSE: To investigate the effects of various 5-fluorouracil (5-FU)
      concentrations, exposure times, and application techniques on in vitro-cultured
      human corneal cells. METHODS: Human corneal epithelial cell (HCEC) and human
      corneal keratocyte (HCK) cultures were exposed to different 5-FU concentrations
      (0.025%-1%) and incubation durations (5 minutes to 2 hours). The cytostatic
      effect was evaluated as the percentage of inhibition of migration relative to the
      control. The evaluation of cytotoxic effect included both phase contrast
      microscopic observations and viability measures performed using an MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] colorimetric assay. The
      results are expressed as ratio of optical density (OD) reduction 24 hours after
      exposure. RESULTS: The cytostatic effect was time and dose dependent. The 50%
      inhibiting dose was 0.55% after 1 hour of incubation for HCECs and was 0.5% after
      2 hours of incubation for HCKs. A 100% inhibitory effect was never observed at
      any concentration or incubation duration. No cytotoxic changes were observed
      using an 5-FU concentration of <1%; 1% 5-FU showed time-dependent cytotoxic
      changes in HCEC cultures only. MTT analysis showed no OD reduction at 5-FU
      concentrations of <1%, whereas 1% 5-FU showed OD reduction <50% at any tested
      exposure time. HCECs showed higher reduction in OD than HCKs. CONCLUSIONS: 5-FU
      formulations topically used in clinical practice showed limited toxicity in
      normal cultured corneal epithelial cells and keratocytes.

PMID- 22968359
TI  - Internal view of the effects of the big-bubble technique during experimental deep
      anterior lamellar keratoplasty.
AB  - PURPOSE: To determine how the air bubble dissects Descemet membrane from the
      inside during experimental deep lamellar anterior keratoplasty. METHODS: In this
      experimental study, 4 corneas from enucleated human eyes were dissected and
      placed in an artificial anterior chamber. Air was injected through a 27-gauge
      needle into the midperiphery without previous trephination until a big bubble
      formed. The results were photographed from the inside. RESULTS: The edge of the
      air dissection was viewed clearly. The dissection was not uniform; one side was
      dissected more than the other. Descemet membrane and the stroma may still have
      been attached. The results provided a clue about why perforation frequently
      occurs when dissecting the anterior lamella in the periphery. CONCLUSION: As much
      air as possible should be injected. Premature cessation of the injection of air
      can result in irregular dissection by all edges of the bubble or an incomplete
      bubble.

PMID- 22968360
TI  - Risk factors for donor cornea contamination:  retrospective analysis of 4546
      procured corneas in a single eye bank.
AB  - PURPOSE: Microbiological contamination is a common cause for elimination of organ
      cultured donor corneas. The aims of the present study were to analyze
      contamination rates and identify risk factors for contamination. METHODS:
      Retrospectively, the contamination rates of 4546 organ-cultured corneas and the
      causative species were studied. The impact of sex, age, death-to-explantation
      interval, explantation technique, cause of death, and mean monthly temperature on
      contamination rate was analyzed. RESULTS: The median annual contamination rate
      was 5.3% (range: 3%-19%). Most contaminations were of fungal origin (61.9%), with
      Candida species (45%) being predominant. Bacterial contaminations (34.4%) were
      dominated by Staphylococcus species (12.8%). Sex, donor age, and mean monthly
      temperature had no statistically significant influence on the contamination rate.
      The median death-to-explantation interval of contaminated corneas (44 hours) was
      longer than that of sterile corneas (39 hours; P < 0.001; n = 4437).
      Cardiopulmonary failure was associated with the highest contamination rate
      (13.6%) of all death causes. The switch from whole globe to in situ excision was
      followed by a temporary increase in contamination rate (12.5%-19.4%).
      CONCLUSIONS: Although the genesis of donor cornea contamination seems to be
      multifactorial, resident species from physiological skin flora are the main
      contaminants indicating that the donor corpses could be the main source of
      microbiological contamination. A change in the explantation technique was
      followed by an increase in the contamination rate.

PMID- 22968361
TI  - Correlation between signs and symptoms of ocular surface dysfunction and tear
      osmolarity with ambient levels of air pollution in a large metropolitan area.
AB  - PURPOSE: To evaluate the effect of high levels of environmental air pollution on
      tear osmolarity and its possible correlation with clinical signs and symptoms.
      METHODS: This was a panel study involving 71 taxi drivers and traffic controllers
      from Sao Paulo, Brazil. Mean individual levels of 24-hour exposure to nitrogen
      dioxide (NO2) and particulate matter smaller than 2.5 MUm (PM2.5) were assessed
      on 4 different occasions. On the first and third visits, subjects were submitted
      to clinical evaluations including the administration of the Ocular Surface
      Disease Index questionnaire, slit-lamp examination, estimation of tear breakup
      time (BUT), the Schirmer test, and vital staining of the cornea and conjunctiva.
      On the second and fourth visits, tear samples were collected for osmolarity
      assays. Statistical analysis was performed using generalized estimating
      equations. RESULTS: Although the taxi drivers and traffic controllers in our
      sample were exposed to high levels of NO2 and PM2.5, few symptoms were reported
      on the Ocular Surface Disease Index questionnaire. BUT values were reduced,
      whereas vital staining and Schirmer test mean results were within normal limits,
      despite considerable variability. A significant and negative correlation was
      found between PM2.5 levels and tear film osmolarity levels (P < 0.05). An
      increase of 10 MUg/m(3) in PM2.5 was associated with a 10.9 mOsm/kg decrease in
      tear osmolarity. There also was a negative correlation, although not
      statistically significant, between NO2 and tear osmolarity. CONCLUSIONS: Exposure
      to air pollution reduces tear film stability and influences tear film osmolarity.
      Combining clinical examination with the assessment of tear osmolarity may help
      understand ocular surface response to high levels of air pollution.

PMID- 22968362
TI  - Beveled femtosecond laser astigmatic keratotomy for the treatment of high
      astigmatism post-penetrating keratoplasty.
AB  - PURPOSE: To use beveled femtosecond laser astigmatic keratotomy (FLAK) incisions
      to treat high astigmatism after penetrating keratoplasty. METHODS: Paired FLAK
      incisions at a bevel angle of 135 degrees, 65% to 75% depth, and arc lengths of
      60 to 90 degrees were performed using a femtosecond laser. One case of
      perpendicular FLAK was presented for comparison. Vector analysis was used to
      calculate the changes in astigmatism. Fourier domain optical coherence tomography
      was used to examine incision morphology. RESULTS: Wound gaping requiring suturing
      was observed in the case of perpendicular FLAK. Six consecutive cases of beveled
      FLAK were analyzed. Fourier domain optical coherence tomography showed that
      beveled FLAK caused a mean forward shift of Bowman layer anterior to the
      incisions of 126 +/- 38 MUm, with no wound gaping. The mean magnitude of
      preoperative keratometric astigmatism was 9.8 +/- 2.9 diopters (D), and
      postoperatively it was 4.5 +/- 3.2 D (P < 0.05). Uncorrected visual acuity
      improved from 1.24 +/- 0.13 logarithm of the minimum angle of resolution
      preoperatively to 0.76 +/- 0.38 postoperatively (P < 0.05). Best spectacle
      corrected visual acuity improved from 0.43 +/- 0.33 logarithm of the minimum
      angle of resolution preoperatively to 0.27 +/- 0.24 postoperatively (P = 0.22).
      Visual results were reduced in 2 patients by cataract progression. Between 1 and
      3 months after beveled FLAK, the keratometric cylinder was stable (<1 D change)
      in 5 of 6 patients, and regressed in 1 patient. No complications occurred.
      CONCLUSIONS: Beveled FLAK incisions at varied depth are effective in the
      management of postkeratoplasty astigmatism. Early postoperative changes
      stabilized within 1 month in most patients. Further studies are needed to assess
      long-term outcomes.

PMID- 22968363
TI  - Indications, visual outcome, and ectasia in clear corneal transplants 20 years
      old or more.
AB  - PURPOSE: To report the indications, visual outcome, and development of ectasia in
      clear corneal transplants at least 20 years or more after penetrating
      keratoplasty (PK). METHODS: A computer search of all post-PK patients in the
      electronic medical records of the Cornea Service was done. Only patients with
      clear primary grafts aged 20 years or more were included. Main outcome measures
      noted were indications for surgery, final visual outcome, and postoperative
      complications. A subset of patients who developed ectasia clinically was also
      analyzed. RESULTS: One hundred forty-nine eyes of 109 patients were identified.
      The most common indication was keratoconus (76.5%). After average follow-up of 27
      years, the mean postoperative best-corrected visual acuity was 0.29 +/- 0.38
      logarithm of the minimum angle of resolution (Snellen equivalent 20/39).
      Postoperative complications included rejection (29.5%), cataract formation
      (26.2%), and steroid-induced elevated intraocular pressure (15.4%). Peripheral
      thinning and ectasia diagnosed by slit lamp were noted in 59 eyes (39.6%), most
      of which were mild (54.2%), inferiorly located (66.1%), and involved the graft
      host junction (81.4%). Most of the grafts that developed ectasia had a
      preoperative diagnosis of keratoconus (91.5%). Mean postoperative visual acuity
      of ectatic grafts with rigid gas permeable contact lens and/or glasses was 0.24
      +/- 0.25 logarithm of the minimum angle of resolution (Snellen equivalent 20/34).
      CONCLUSION: PK grafts can remain clear for 20 years or more and have excellent
      visual outcome. Most of the 20-year-old grafts in our study were in patients with
      keratoconus. Rejection and graft-host ectasia are problems to be encountered in
      long-surviving grafts. Ectatic grafts can still attain good vision with properly
      fitted contact lenses and glasses.

PMID- 22968364
TI  - Ruthenium complexes containing 2,6-bis(benzimidazolyl)pyridine derivatives induce
      cancer cell apoptosis by triggering DNA damage-mediated p53 phosphorylation.
AB  - DNA has been identified as a primary target for anticancer drug design and
      remains one of the most promising biological receptors for the development of
      chemotherapeutic agents. We have previously demonstrated that ruthenium complex
      [Ru(bmbp)(phen)Cl]ClO(4) (RuBmP; bmbp = 2,6-bis(4-methylbenzimidazol-2
      yl)pyridine) is a novel apoptosis-inducer by triggering mitochondria-mediated ROS
      overproduction in cancer cells. In the present work, the underlying mechanisms of
      the anticancer action of RuBmP were further elucidated by evaluating its DNA
      interaction properties and the regulating signalling pathways. Our results showed
      that RuBmP could effectively activate DNA strand breaks in A375 cells in a dose
      dependent manner after cellular internalization. Phosphorylation of a DNA damage
      marker Histone H2A.X (Ser139) was thus up-regulated in treated cells. DNA damage
      subsequently activated p53 phosphorylation and inhibited the expression of Bcl
      xL, resulting in activation of caspase-3, -8 and -9, and cleavage of poly(ADP
      ribose) polymerase (PARP). The interactions between the complexes and cancer cell
      chromosomal and calf thymus DNA were characterized by UV-vis absorption,
      fluorescence intensity and viscosity measurements, which clearly demonstrated the
      intercalative binding of the complexes to DNA. Taken together, these results
      suggest that RuBmP, as a promising anticancer agent, induces cancer cell
      apoptosis by triggering DNA damage-mediated p53 phosphorylation.

PMID- 22968365
TI  - [Treatment of nausea and vomiting with prokinetics and neuroleptics in palliative
      care patients : a review].
AB  - BACKGROUND: Many recommendations concerning the treatment of nausea and vomiting
      in palliative care patients exist but what is the evidence for this? Most studies
      dealing with this topic have focused on cancer patients under chemotherapy and/or
      radiation therapy or on patients with postoperative nausea. Cancer patients
      without chemotherapy or radiation therapy, patients without postoperative nausea,
      and patients having other diseases with palliative care aspects, such as acquired
      immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease (COPD),
      progressive heart failure, amyotrophic lateral sclerosis (ALS) and multiple
      sclerosis (MS) have been underrepresented in studies on nausea and vomiting so
      far. OBJECTIVES: The aim of this review was to determine the level of evidence
      for the treatment of nausea and vomiting with prokinetics and neuroleptics in
      palliative care patients suffering from far advanced cancer and no longer being
      treated with chemotherapy or radiation therapy, AIDS, COPD, progressive heart
      failure, ALS or MS. METHODS: Two different electronic databases (PubMed und
      Embase) were used to identify studies. Furthermore, a hand search for related
      articles was performed. No restriction was made concerning study types. Studies
      with patients undergoing chemotherapy radiation therapy or suffering from
      postoperative nausea, pediatric studies and studies published neither in English
      nor in German were excluded. RESULTS: A total of 30 studies fulfilling the
      inclusion criteria were found. All studies focused on cancer patients. Despite
      intensive research studies in patients with AIDS, COPD, heart failure, ALS or MS
      were not detected. Metoclopramide is seen as an effective drug in many studies
      whereas the evidence for it is moderate at best. Within the group of
      neuroleptics, levosupiride and levomepromazine seem to have good antiemetic
      potential but the evidence level is low. CONCLUSION: In patients with advanced
      cancer not being treated with chemotherapy or radiation therapy, metoclopramide
      can be used to reduce nausea and vomiting. Neuroleptics, such as levosulpiride or
      levomepromazine are alternatives but their adverse effects have to be considered
      carefully. The evidence level for prokinetics and neuroleptics is moderate to
      low. Concerning palliative care of patients with diseases other than cancer no
      studies exist. More well designed studies in palliative care patients are needed
      in order to facilitate evidence based antiemetic therapy. The English full text
      version of this article will be available in SpringerLink as of November 2012
      (under "Supplemental").

PMID- 22968366
TI  - [Antidepressants for treatment of depression in palliative patients : a
      systematic literature review].
AB  - BACKGROUND: Treatment of depression in palliative care must take into account
      expected benefits and risks of antidepressants in patients with potentially
      limited life expectancy, poor medical condition, advanced age and higher risk to
      suffer from side effects and drug interactions. This systematic review assesses
      evidence of the efficacy and safety of different classes of antidepressants
      depending on the type and severity of the physical illness. METHODS: A systematic
      database search (Medline, EMBASE) for clinical studies was carried out and
      references of identified literature were checked. To be included in the review
      studies had to be performed in illnesses that were part of in the search
      strategy, such as multiple sclerosis, Parkinson's disease, Alzheimer's disease,
      HIV/AIDS, cancer, COPD and heart failure. Considered were controlled studies
      comparing the efficacy of antidepressants to placebo, other classes of
      antidepressants, benzodiazepines, psychostimulants or psychotherapy. In a first
      step only studies with patients meeting established diagnostic criteria of
      depression and where depression was a primary endpoint were included. In a second
      step, additional studies were included that did not meet both of the latter
      criteria but were performed in patients at the end of life. RESULTS: A total of
      40 trials (mostly using SSRI or NSMRI) were included, 16 studies were performed
      in neurological, 24 in general medical conditions and 9 studies were performed in
      patients at the end of life or in advanced disease stages. Due to heterogeneous
      study designs no conclusions can be drawn if efficacy or tolerability is
      dependent on disease severity. In most cases, studies might have been too small
      to detect limited treatment effects. As a lack of efficacy was predominantly
      shown in larger trials, publication bias might have been present. In most of the
      reviewed general medical conditions study results were heterogeneous. In contrast
      to the popularity of the treatment approach, results suggest that SSRIs are not
      effective in Alzheimer's disease. In Parkinson's disease, negative studies are
      too small to prove lack of efficacy of SSRIs as present in the majority of
      trials. CONCLUSIONS: This review of the evidence allows only limited conclusions
      concerning the use of antidepressants in physical illness disorders at the end of
      life. The reviewed evidence does not allow direct conclusions to be drawn
      concerning the use of antidepressants in different disease severities and its
      benefits compared to other treatment options (psychotherapy, benzodiazepines
      etc.). The English full text version of this article will be available in
      SpringerLink as of November 2012 (under "Supplemental").

PMID- 22968368
TI  - Primary knee replacement for primary osteoarthritis in the aged: gender
      differences in epidemiology and preoperative clinical state.
AB  - BACKGROUND AND AIMS: The purpose of this study was to calculate the incidence of
      primary knee replacements for osteoarthritis (OA) and to compare preoperative
      clinical situation between men and women aged >=80 years. Patients aged 75-79
      formed a comparison group. METHODS: We retrospectively reviewed a population
      based series of 1396 primary knee replacements performed due to primary OA in a
      joint replacement hospital between 2002 and 2008. Preoperative clinical data were
      recorded prospectively into a joint replacement database. Data on preoperative
      clinical situation (e.g. deformities, mobility level and clinical knee scores)
      was compared between the age groups, and between genders within both age groups.
      RESULTS: The incidence of primary knee replacements performed due to OA in
      patients aged >=80 years increased from 553/100,000 in 2003 to 785/100,000 in
      2007. After adjustment for age, gender, anesthesiological risk score and
      laterality of OA, both age of >=80 years and female gender were associated with
      higher probability of using walking aids and inability to climb stairs. Age but
      not gender was associated with walking distance and presence of severe axial
      deformity and severe antero-posterior instability. Female gender but not age
      showed association with pain, medio-lateral instability and poor preoperative
      clinical knee scores. CONCLUSIONS: Patients aged >=80 years and particularly
      women present with higher mobility restriction and more progressed OA at the time
      of primary knee replacement. Barriers restricting access to surgery should be
      identified and removed to improve the care of older patients with severe knee OA.

PMID- 22968367
TI  - [Drug therapy of anxiety and fear in palliative care patients with cancer or
      other illnesses : a systematic review].
AB  - BACKGROUND: Pharmacological treatment of anxiety is an important part of drug
      treatment in palliative care. In this review we searched for the current evidence
      of pharmacological treatment of anxiety in palliative care. MATERIALS AND
      METHODS: A systematic search of PubMed, Embase, PsycLIT, PsycINFO, CINAHL for
      studies of anxiety in palliative care was carried out in January 2012.
      Furthermore we searched the Cochrane Library, references of literature and
      leading textbooks. Studies were identified and information was filled in a
      standardized extraction sheet. Studies have been categorized and anxiety as an
      endpoint determined. RESULTS: A total of four controlled studies, three
      uncontrolled studies, two retrospective studies, one case report, two surveys,
      one systematic Cochrane review and one unsystematic review were analyzed and
      included in this review. This indicates an overall low number of studies for the
      pharmacological treatment of anxiety in palliative care. According to our
      results, benzodiazepines are the most commonly used drugs in palliative care.
      However, based on our review, there is no evidence-based recommendation for the
      therapeutic use in palliative care. CONCLUSIONS: With the existing evidence no
      general recommendations for pharmacological treatment of anxiety in palliative
      care can be given. Even for the commonly used benzodiazepines, neuroleptics,
      antidepressants, antihistamines and beta blockers for the treatment of anxiety no
      evidence based recommendations can be made. However, these medications are
      commonly used to treat anxiety in other patient populations and can also be used
      in palliative care patients. According to our review we cannot recommend a single
      drug or give recommendations regarding the dosage of drugs. There is a strong
      need for randomized controlled trials to evaluate the effect of drug treatment of
      anxiety in palliative care patients. The English full text version of this
      article will be available in SpringerLink as of November 2012 (under
      "Supplemental").

PMID- 22968370
TI  - Anatase TiO2 pillar-nanoparticle composite fabricated by layer-by-layer assembly
      for high-efficiency dye-sensitized solar cells.
AB  - The anatase TiO(2) pillar (PL)-TiO(2) nanoparticle (NP) composite is fabricated
      via layer-by-layer assembly. The composition of the nanostructures (i.e. the
      pillar-to-nanoparticle ratio) can be conveniently tuned by controlling the
      experimental conditions of the layer-by-layer assembly. It has been used to
      fabricate photoelectrodes for high-efficiency dye-sensitized solar cells (DSSCs),
      which combine the advantages of the rapid electron transport in PLs with the high
      surface area of NPs. It was found that, with optimum preparation conditions,
      DSSCs with the composite photoelectrode show a better photoelectrical conversion
      efficiency (8.06%) than those with either the naked PL photoelectrode or the
      mechanically mixed PL-NP photoelectrode. This is explained by the photoelectron
      injection drive force and the interfacial electron transport of the DSSCs, which
      are quantitatively characterized using the surface photovoltage spectra and
      electrochemical impedance spectroscopy measurements. It is evident that the DSSC
      with the optimal PL/NP ratio displays the largest photoelectron injection drive
      force and the fastest interfacial electron transfer.

PMID- 22968371
TI  - Dissecting paracrine effectors for mesenchymal stem cells.
AB  - There has been increasing interest in the application of mesenchymal stem cells
      (MSCs) in regenerative medicine in recent years. In this context, the beneficial
      effects of MSCs have been ascribed mainly to a paracrine action rather than to
      direct replacement of the injured tissue. Indeed, MSCs produce a great variety of
      trophic and immunomodulatory factors. In this chapter, we provide an overview of
      growth factors and chemokines involved in stimulation of cell proliferation,
      inhibition of apoptosis, enhancement of angiogenesis, and suppression of
      inflammatory and immune response. In addition, we discuss the emerging role of
      the extracellular vesicles released from MSCs as possible paracrine mediators.

PMID- 22968369
TI  - Neuropathologically defined subtypes of Alzheimer's disease differ significantly
      from neurofibrillary tangle-predominant dementia.
AB  - Alzheimer's disease (AD) can be classified based on the relative density of
      neurofibrillary tangles (NFTs) in the hippocampus and association cortices into
      three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic
      predominant AD (LP AD). AD subtypes not only have pathologic, but also
      demographic, clinical, and genetic differences. Neurofibrillary tangle
      predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic
      structures, shares this feature with LP AD raising the possibility that NFTD is a
      variant of AD. The objective criteria for pathologic diagnosis of NFTD are not
      available. A goal of this study was to design a mathematical algorithm that could
      diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and
      association cortices, analogous to that used to subtype AD. Moreover, we aimed to
      compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18)
      with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and
      HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho
      tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT
      densities and showed expected patterns across AD subtypes. HpSp AD had the
      highest and LP AD had the lowest burden of cortical CP13 and Ab39
      immunoreactivity. On the other hand, cortical beta-amyloid burden did not
      significantly differ between AD subtypes. Semi-quantitative assessment of SPs in
      the basal ganglia did show HpSp AD to have significantly more frequent presence
      of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP
      AD, NFTD had an older age at disease onset and shorter disease duration, as well
      as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as
      well as CP13, Ab39, and Abeta immunoreactivities were very low in the frontal
      cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1
      genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD,
      while APOE epsilon4 carrier state was low in NFTD. While it shares clinical
      similarities with regard to female sex predominance, onset in advanced age, and a
      slow cognitive decline, NFTD has significant pathologic differences from LP AD,
      suggesting that it may not merely be a variant of AD.

PMID- 22968372
TI  - Surface modification of the TiO2 nanoparticle surface enables fluorescence
      monitoring of aggregation and enhanced photoreactivity.
AB  - Chemically and biologically modified nanoparticles are increasingly considered as
      viable and multifunctional tools to be used in cancer theranostics. Herein, we
      demonstrate that coordination of alizarin blue black B (ABBB) to the TiO(2)
      nanoparticle surface enhances the resulting nanoparticles by (1) creating
      distinct fluorescence emission spectra that differentiate smaller TiO(2)
      nanoparticles from larger TiO(2) nanoparticle aggregates (both in vitro and
      intracellular) and (2) enhancing visible light activation of TiO(2) nanoparticles
      above previously described methods to induce in vitro and intracellular damage to
      DNA and other targets. ABBB-TiO(2) nanoparticles are characterized through
      sedimentation, spectral absorbance, and gel electrophoresis. The possible
      coordination modes of ABBB to the TiO(2) nanoparticle surface are modeled by
      computational methods. Fluorescence emission spectroscopy studies indicate that
      ABBB coordination on TiO(2) nanoparticles enables discernment between
      nanoparticles and nanoparticle aggregates both in vitro and intracellular through
      fluorescence confocal microscopy. Visible light activated ABBB-TiO(2)
      nanoparticles are capable of inflicting increased DNA cleavage through localized
      production of reactive oxygen species as visualized by plasmid DNA damage
      detected through gel electrophoresis and atomic force microscopy. Finally,
      visible light excited ABBB-TiO(2) nanoparticles are capable of inflicting damage
      upon HeLa (cervical cancer) cells by inducing alterations in DNA structure and
      membrane associated proteins. The multifunctional abilities of these ABBB-TiO(2)
      nanoparticles to visualize and monitor aggregation in real time, as well as
      inflict visible light triggered damage upon cancer targets will enhance the use
      of TiO(2) nanoparticles in cancer theranostics.

PMID- 22968373
TI  - Functional properties of some New Zealand fruit extracts towards selected
      probiotic and pathogenic bacteria.
AB  - The functional properties of aqueous extracts of four fruits commonly consumed in
      New Zealand, namely blueberry, strawberry, green kiwifruit and feijoa, towards
      the growth of probiotic and pathogenic bacteria were investigated in this study.
      A concentration range of 0.1-30.0 g/l was evaluated in a high-throughput assay to
      determine their effects. In general, the four fruit extracts exerted growth
      stimulating effects on the probiotic bacteria, except with Bifidobacterium
      longum, whereas they were found to inhibit all pathogens tested. Feijoa extract
      inhibited Listeria monocytogenes and Bacillus cereus even at the lowest
      concentrations tested. Selected combinations of extracts (blueberry/feijoa and
      strawberry/kiwifruit) exerted effects that were less than additive compared to
      the individual extracts. These results are relevant for potential application of
      fruit extracts not only as functional ingredients in food but also for
      controlling growth of pathogens and for propagation of probiotic bacteria during
      food production and storage.

PMID- 22968376
TI  - Celebrating Orthopaedic Nurses Day.

PMID- 22968374
TI  - Gram-negative bacteria account for main differences between faecal microbiota
      from patients with ulcerative colitis and healthy controls.
AB  - Detailed knowledge about the composition of the intestinal microbiota may be
      critical to unravel the pathogenesis of ulcerative colitis (UC), a human chronic
      inflammatory bowel disease, since the intestinal microbes are expected to
      influence some of the key mechanisms involved in the inflammatory process of the
      gut mucosa. The aim of this study was to investigate the faecal microbiota in
      patients either with UC in remission (n=6) or with active disease (n=6), and in
      healthy controls (n=6). The composition of Gram-negative bacteria and Gram
      positive bacteria was examined. Antigenic structures of Gram-negative bacteria
      such as lipopolysaccharides have been related to the inflammatory responses and
      pathogenesis of inflammatory bowel disease. Dice cluster analysis and principal
      component analysis of faecal microbiota profiles obtained by denaturing gradient
      gel electrophoresis and quantitative PCR, respectively, revealed that the
      composition of faecal bacteria from UC patients with active disease differed from
      the healthy controls and that this difference should be ascribed to Gram-negative
      bacteria. The analysis did not show any clear grouping of UC patients in
      remission. Even with the relatively low number of subjects in each group, we were
      able to detect a statistically significant underrepresentation of Lactobacillus
      spp. and Akkermansia muciniphila in UC patients with clinically active disease
      compared to the healthy controls. In line with previous communications, we have
      shown that the microbiota in UC patients with active disease differ from that in
      healthy controls. Our findings indicate that alterations in the composition of
      the Gram-negative bacterial population, as well as reduced numbers of
      lactobacilli and A. muciniphila may play a role in UC.

PMID- 22968375
TI  - Cholangiocarcinoma treatment.
AB  - Cholangiocarcinoma (CCA) is a tumor of the bile ducts that usually presents with
      biliary obstruction and has a poor prognosis. The treatment of CCA is challenging
      as the tumor is usually diagnosed late and the treatments are not very effective
      except when complete surgical resection is possible. In carefully selected
      patients, liver transplant can be a curative therapy. In the majority of cases,
      complete surgical resection is not possible and palliation is the mainstay of
      treatment. Stenting, using plastic or metallic stents, allows for biliary
      drainage. Photodynamic therapy plays a role in palliation and might play a role
      in adjuvant or neoadjuvant therapy. While radiation and chemotherapy can be
      beneficial, newer ablative techniques and targeted chemotherapies are promising.

PMID- 22968378
TI  - Developing a progressive mobility activity protocol.
AB  - Orthopaedic nurses specialize in preventing musculoskeletal disorders and
      complications in postoperative patients through early mobility. A review of the
      literature reveals recent studies that discuss the benefits of early mobility in
      intensive care patients. Early progressive mobility programs use a systematic
      progression of activity to prevent deconditioning and its complications in
      critically ill patients. Increasing patient mobility in the intensive care unit
      can help the orthopaedic nurse continue the promotion of wellness and self-care
      and the prevention of injury in the care of individuals with musculoskeletal
      disorders. This article includes a description of the development of an
      innovative progressive mobility activity protocol for intensive care unit
      patients in a community hospital, using a detailed, methodical approach to
      identify the need for practice change and to create a plan for achieving this
      change.

PMID- 22968380
TI  - Understanding the new emerging oral anticoagulants for venous thromboembolism
      prophylaxis.
AB  - Patients who have major orthopaedic surgery are at high risk for developing
      venous thromboembolism (VTE). Assessment of risk and treatment to prevent VTE are
      considered standard of care due to its significant morbidity, potential
      mortality, and clinical burden and cost. Guidelines are available aiding
      orthopaedic surgeons to choose the best methods of VTE prophylaxis. Optimal VTE
      prevention has not been achieved. Recent advances in the understanding of the
      coagulation cascade have evolved because of a novel understanding of the
      molecular influences on the coagulation pathway. Subsequently, new anticoagulants
      have been developed that target specific factors within the coagulation cascade
      that are contrasted to the currently used agents that have a broad effect on the
      coagulation pathway. Multiple clinical trials have tested the new anticoagulants
      within the orthopaedic total knee and total hip arthroplasty arena. In addition,
      research to find new ways to prevent VTE was driven by limitations of the
      currently available agents. The new oral anticoagulants extensively trialed in
      orthopaedics are dabigatran, rivaroxaban, and apixaban. Clinical trials indicate
      that the new oral agents have the potential to impact VTE prophylaxis in regard
      to efficacy, predictability and consistency, clinical monitoring, adherence as to
      use and duration, and convenience. Concerns persist regarding issues of bleeding
      complications, liver enzyme elevation, patients with renal disease, and drug-to
      drug interactions. The new oral agents do not have an antidote to reverse
      bleeding effect and have no reliable assay to measure effect. Nurses need to be
      aware of these new VTE prophylactic choices and their implications in order to
      provide the best outcomes for their patients.

PMID- 22968382
TI  - Preoperative care management of patients with hip fractures during the wait time
      between emergency department discharge and operating room admission for surgical
      repair.
AB  - BACKGROUND: Recognizing a patient's needs during the emergency department to
      operating room interval is crucial to identify areas for improvement. A review of
      the literature provided no pertinent research regarding this phase of the
      preoperative experience. PURPOSE: This descriptive study examined the
      preoperative care management of patients with hip fractures during the wait time
      between emergency department discharge and operating room admission. METHOD: Data
      were collected through a systematic retrospective chart review. Demographic
      variables included gender, age, and comorbidities. Preoperative patient variables
      included type of analgesia, level of pain, antiembolism interventions, fluid
      intake, sensory perception/cognition, mobility, and nutritional intake. Subjects
      were patients cared for at 3 sites in a large multihospital system. A total of
      137 charts were reviewed. FINDINGS: Although findings were not statistically
      significant, opportunities to improve care were identified. More attention is
      needed to evaluate patients effectively for pain, particularly where there are
      cognitive deficits. Designing and implementing a program for increased bed
      mobility and protocols that closely monitor and manage fluid intake may offset
      postoperative complications.

PMID- 22968383
TI  - Bone up your program: certification process for the total knee replacement and
      total hip replacement center.
AB  - Knee and hip osteoarthritis, combined with the increased aging population,
      obesity, and other health-related risk factors, has led to a great need for joint
      replacement procedures. Joint replacement programs have been developed within
      hospitals to meet this demand. Joint replacement programs have been designed to
      provide an efficient and structured delivery of care. Facilities can demonstrate,
      to those seeking care, their quality programs by applying for and obtaining
      certification. Joint replacement certifications can guide facilities in providing
      a solid structure of improved care, quality, and superior outcomes. This article
      describes the steps that a community hospital took to attain the Blue Distinction
      Centers for Knee and Hip Replacement as well as The Joint Commission Disease
      Specific Care Certification in Total Knee Replacement and Total Hip Replacement.

PMID- 22968385
TI  - The American Joint Replacement Registry.
AB  - The cost of healthcare procedures is continuously rising and more emphasis is
      being placed on increasing the quality and effectiveness of healthcare services.
      A combined total of 711,000 hip and knee arthroplasties are performed yearly.
      This figure is expected to increase to 4 million by the year 2030. The American
      Joint Replacement Registry has been developed to monitor the performance of
      devices, determine the cost-effectiveness of procedures, and increase patient
      safety for individuals in need of hip and knee replacement procedures.

PMID- 22968388
TI  - Postoperative psychological distress in patients having total hip or knee
      replacements: an exploratory panel study.
AB  - PURPOSE: The purpose of this study was to describe postoperative anxiety and
      depression in patients undergoing total hip or knee replacement, describe and
      identify preexisting factors known during hospitalization and postdischarge, and
      detect associations with symptoms of anxiety and depression at home at least 4
      weeks posthospital discharge. METHODS: Patients from 2 sites in Iceland answered
      self-administered questionnaires at the hospital and at home. The questionnaires
      included questions about anxiety, depression, pain, family and social situations,
      and hospital and illness experience. FINDINGS: Patients exhibited few symptoms of
      anxiety and depression. Significant associations between symptoms of anxiety and
      depression at the hospital with anxiety and depression at home, as well as
      between general postoperative symptoms and quality of sleep, were found.
      Postoperative anxiety was predicted by depression at the time of admission to the
      hospital. Postoperative depression was predicted by depression at the hospital
      and presence of pain at home. Most patients found that the operation was as
      successful as expected; 29.6% stated that they had recovered very well and 33.6%
      wanted more information about the time it takes to recover.

PMID- 22968391
TI  - Population structure in a wheat core collection and genomic loci associated with
      yield under contrasting environments.
AB  - A set of 96 winter wheat accessions sampled from a variety of geographic origins,
      including cultivars and breeding lines, were characterized with 46 genome-wide
      SSR loci for genetic diversity and population structure. The genetic diversity
      within these accessions was examined using a genetic distance-based and a model
      based clustering method. The model-based analysis identified an underlying
      population structure comprising of four distinct sub-populations which
      corresponded well with distance-based groupings. Information on the population
      structure is taken into account in an association mapping study of grain yield
      from a 3-years field trial incorporating fully irrigated, rainfed and drought
      stress treatments. A total of 21 marker-grain yield associations (P < 0.01) were
      identified with nine SSR markers. Most associations were detected only in one to
      three environments (treatment/year combination), with an average R ( 2 ) value
      around 13 %. However, marker gwm484 (on chromosome 2D) was associated with yield
      in six environments, including irrigated, rainfed and drought stress treatments,
      suggesting it could be used to improve grain yield across a range of
      environments. Variation in grain yield at this locus was associated with
      earliness, early vigour, kernels per spikelet and harvest index. Microsatellite
      locus psp3200 (on chromosome 6D) was associated with yield in dry and hot
      environments, which was related to earliness, early vigour, productive tillering
      and total biomass per plant. Partial least squares regression, with nine
      environmental factors, showed that precipitation from tillering to maturity was
      the main environmental factor causing marker * environment associations for grain
      yield.

PMID- 22968392
TI  - The photophysics of porous silicon: technological and biomedical implications.
AB  - Although porous silicon (pSi) was first obtained in the mid-20th century,
      considerable interest in this material arose much later, due to the discovery of
      its room-temperature photoluminescence (PL). In the 1990s, most studies on pSi
      were focused on the analysis and explanation of its photoluminescent and
      electroluminescent characteristics and their potential practical applications.
      The latest advances in pSi research are related to its biocompatibility and
      biomedical applications. The discovery of singlet oxygen generation by pSi
      through nonradiative transfer of photoexcitation energy has opened new prospects
      for photodynamic therapy in vivo, and the discovery of laser
      desorption/ionization on pSi has paved the way for advanced approaches in mass
      spectrometry. In this study, the main photophysical properties of pSi are
      reviewed, and a wide range of photo-processes characteristic of pSi and their
      practical implications are analyzed in terms of the general principles of energy
      and charge transfer. Special attention is paid to the possible applications of
      pSi and pSi-based nanocomposites in photonics, biophysics, medicine, and
      analytical chemistry.

PMID- 22968394
TI  - [When the resting membrane potential becomes restless. Acute hyperkalemia in the
      perioperative phase].
AB  - Acute hyperkalemia is a life-threatening event and often occurs abruptly and
      without warning in the perioperative field. Risk factors are found on multiple
      levels as they can derive from a patients pre-existing condition or result from
      the surgical intervention or management of anesthesia. The therapy of
      hyperkalemia depends on the dimensions of electrolyte disturbance and a
      distinction can be made between therapeutic measures with a rapid and those with
      a long-term effect.

PMID- 22968393
TI  - Expression of tyrosine kinase receptors in cultured dorsal root ganglion neurons
      in the presence of monosialoganglioside and skeletal muscle cells.
AB  - The neurotrophic factor-like activity of monosialoganglioside (GM1) has been
      shown to activate tyrosine kinase receptors (Trk). Targets of neuronal
      innervation play a vital role in regulating the survival and differentiation of
      innervating neurotrophin-responsive neurons. Both GM1 and target skeletal muscle
      (SKM) cells are essential for the maintenance of the function of neurons.
      However, much less is known about the effects of GM1 or/and target SKM cells on
      the expression of Trk receptors in dorsal root ganglion (DRG) neurons. Here we
      have tested what extent to the expression of TrkA, TrkB, and TrkC receptors in
      primary cultured of DRG neurons in absence or presence of GM1 or/and SKM cells.
      In this experiment, we found that: (1) GM1 promoted expression of TrkA and TrkB
      but not TrkC in primary cultured DRG neurons; (2) target SKM cells promoted
      expression of TrkC but not TrkA and TrkB in neuromuscular cocultures without GM1
      treatment; and (3) GM1 and target SKM cells had additional effects on expression
      of these three Trk receptors. The results of the present study offered new clues
      for a better understanding of the association of GM1 and target SKM on the
      expression of Trk receptors.

PMID- 22968395
TI  - Frequencies of BCL2 and BCL6 translocations in representative Chinese follicular
      lymphoma patients: morphologic, immunohistochemical, and FISH analyses.
AB  - The most common genetic aberration in follicular lymphoma (FL) is the
      t(14;18)(q32;q21) translocation that juxtaposes the antiapoptotic BCL2 gene with
      the promoter of the immunoglobulin heavy-chain (IgH) gene, which is the molecular
      hallmark of FL, whereas a subset of cases harbor translocations involving the
      BCL6 gene locus. To date, there has been no integrated analysis based on grade,
      phenotype, and genotype from large numbers of FL cases in a representative
      Chinese population. In this study, we graded 98 FL cases; fluorescence in situ
      hybridization was used to determine the BCL2 and BCL6 translocation statuses, and
      these were compared with morphologic and immunohistochemical parameters. The
      expressions of the 4 antigens were B-cell leukemia/lymphoma (BCL)-2(88.8%), BCL
      6(80.6%), CD10(62.2%), and Ki67(50.0%), respectively. The frequencies of BCL2 and
      BCL6 translocations were 58.5% and 16.3%. In conclusion, the incidence of
      IgH/BCL2-positive FL in Chinese patients is relatively lower compared with that
      in western countries. BCL2 translocation strongly correlated with CD10 and Ki67
      expression. Our data confirm the presence of a relationship between the
      translocation status and the FL histologic grade. All BCL6 translocations
      occurred in high-grade FL, and this suggests that FL carrying BCL6 translocation
      probably constitute a special biological subtype.

PMID- 22968396
TI  - Determinants of risky sexual behavior among injecting drug users (IDUs) in
      Georgia.
AB  - Injection risk practices and risky sexual behaviors place injection drug users
      (IDUs) and their sexual partners particularly vulnerable to HIV. The purpose of
      the study was to describe and understand determinants of high-risk sexual
      behavior among IDUs in Georgia. A cross-sectional, anonymous survey assessed
      knowledge, behavior and HIV status in IDUs in five Georgian cities (Tbilisi,
      Gori, Telavi, Zugdidi, Batumi) in 2009. The study enrolled in total 1,127 (1,112
      males, 15 females) IDUs. Results indicate that occasional sexual relationships
      are common among male IDUs, including married ones. A subsample of 661 male IDUs
      who reported having occasional and paid sex partners during the last 12 months
      was analyzed. Multivariate analysis shows that not having a regular partner in
      the last 12 month (adjusted odds ratio (aOR) 1.57, 95 % CI 1.04 2.37), and using
      previously used needles/syringes at last injecting (aOR 2.37, 95 % I 1.10-5.11)
      are independent correlates of inconsistent condom use with occasional and paid
      sexual partners among IDUs. Buprenorphine injectors have lower odds of
      inconsistent condom use with occasional and paid sexual partners compared to
      heroin injectors (aOR 0.47, 95 % CI 0.27-0.80), and IDUs who live in Telavi are
      twice more likely to engage in such risky sexual behavior than capital city
      residents (aOR 2.55, 95 % CI 1.46-4.48). More effective programs focused on
      sexual risk behavior reduction strategies should be designed and implemented.

PMID- 22968397
TI  - Acceptability and uptake of neonatal male circumcision in Lusaka, Zambia.
AB  - Neonatal male circumcision (NMC) is an uncommon procedure in Southern Africa, but
      is being scaled up in Zambia for long-term HIV prevention. We conducted a cross
      sectional survey on NMC with a convenience sample of mothers of newborn boys at
      two public clinics in Lusaka. Following the survey, mothers received information
      on availability of NMC, and uptake of the service was tracked. Predictors of
      uptake were assessed using bivariate and multivariate logistic regression. Of the
      1,249 eligible mothers approached, 1000 (80%) agreed to participate. Although 97%
      of surveyed mothers said they definitely or probably planned to have their
      newborn son circumcised, only 11% of participants brought their newborn sons for
      NMC. Significant predictors of uptake in adjusted models included: Older maternal
      age (AOR 3.77, 95% CI 1.48-9.63 for age 36 and above compared to mothers age 25
      and below), having attended antenatal care at an NMC site (AOR 2.13, 95% CI 1.32
      3.44), older paternal age (AOR 4.36, 95% CI 1.28-14.91 for age 26-35 compared to
      fathers age 25 and below), and the infant's father being circumcised (AOR 2.21,
      95% CI 1.35-3.62). While acceptability studies in Southern Africa have suggested
      strong support for MC among parents for having their sons circumcised, this may
      not translate to high uptake of newly-introduced NMC services.

PMID- 22968398
TI  - HIV prevalence and sexual risk behaviors associated with awareness of HIV status
      among men who have sex with men in Paris, France.
AB  - A cross-sectional survey, using self-sampled finger-prick blood on blotting paper
      and anonymous behavioral self-administrated questionnaires was conducted in Paris
      in 2009 among MSM attending gay venues. Paired biological results and
      questionnaires were available for 886 participants. HIV seroprevalence was 17.7 %
      (95 % CI: 15.3-20.4). Four groups were identified according to their knowledge of
      their HIV biological status. Among the 157 found to be seropositive, 31 (19.7 %)
      were unaware of their status and reported high levels of sexual risk behaviors
      and frequent HIV testing in the previous 12 months. Among the 729 MSM diagnosed
      HIV-negative, 183 were no longer sure whether they were still HIV-negative, or
      had never been tested despite the fact that they engaged in at-risk sexual
      behaviors. This study provides the first estimate of HIV seroprevalence among MSM
      in Paris and underlines the specific need for combined prevention of HIV
      infection in this MSM population.

PMID- 22968399
TI  - Memory-based strategies for antiretroviral medication management: an evaluation
      of clinical predictors, adherence behavior awareness, and effectiveness.
AB  - "Forgetting" is the most commonly endorsed reason for missing an antiretroviral
      therapy (ART) dose, yet little is known about the prevalence, predictors, and
      effectiveness of the mnemonic strategies to support ART adherence. The current
      study assessed 28 self-reported memory-based medication strategies in 233 HIV
      infected individuals with 30-day ART adherence measured via the medication event
      monitoring system. Participants endorsed using multiple (8.7 +/- 5.6) strategies
      with the most common being internally-driven. More frequent strategy use was
      uniquely associated with affective distress, dependent daily functioning, higher
      non-ART pill burden, and poorer ART adherence. Individuals who used strategies
      frequently, but perceived them as minimally effective, had more affective,
      physical, and functional distress. More frequent strategy use was associated with
      worse ART adherence and was unrelated to perceived effectiveness. Primary
      reliance on internally-based mnemonic strategies may reflect a lack of awareness
      of adherence behaviors and may be insufficient to support optimal ART adherence
      in vulnerable populations.

PMID- 22968400
TI  - The age of reason for FDG PET image-derived indices.

PMID- 22968401
TI  - The preoperative SUVmax is superior to ADCmin of the primary tumour as a
      predictor of disease recurrence and survival in patients with endometrial cancer.
AB  - PURPOSE: The purpose of this study was to investigate the prognostic value of the
      minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted
      MR imaging and of the maximum standardized uptake value (SUVmax) derived from
      PET/CT imaging of the primary tumour in patients with endometrial cancer.
      METHODS: SUVmax reflects the highest tumour metabolism rate and ADCmin reflects
      the highest cellularity, and both parameters have been used for tumour grading
      and prediction of prognosis. The correlations between prognosis and SUVmax and
      ADCmin of the primary tumour were determined in 131 patients with endometrial
      cancer. The patients were divided into groups based on ADCmin and SUVmax cut-off
      values to predict recurrence and survival, which were derived from receiver
      operating characteristic curves. Disease-free survival (DFS) and overall survival
      (OS) of the groups were analysed using the Kaplan-Meier method, and differences
      between survival curves were evaluated using the log-rank test. RESULTS: The
      median DFS and OS times of all patients were 19.2 and 20.5 months (follow-up
      periods 1-70 months for both DFS and OS), respectively. Patients with high SUVmax
      had significantly lower DFS (P < 0.0001) and OS (P = 0.0092) than patients with
      low SUVmax. Multivariate analysis showed that high SUVmax was an independent
      prognostic factor for both DFS (P = 0.0161) and OS (P = 0.0232). CONCLUSION: The
      SUVmax of the primary tumour derived from PET/CT imaging could be an important
      prognostic indicator of recurrence and survival in patients with endometrial
      cancer.

PMID- 22968402
TI  - T-regulatory cells in severe atopic dermatitis: alterations related to cytokines
      and other lymphocyte subpopulations.
AB  - The changes in lymphocyte subpopulations in atopic dermatitis (AD) concern also T
      regulatory cells. We investigated the expression of various surface receptors on
      CD3(+)CD4(+)CD25(high)FoxP3(+) T-regulatory cells and the activation CD28(+)
      receptor and the inhibitory CD152(+) receptor on helper/inducer as well as
      cytotoxic/suppressor T cells. Peripheral blood lymphocytes of 15 AD patients and
      20 healthy subjects were analyzed by flow cytometry using monoclonal antibodies.
      The concentrations of IL-6, IL-10 and TGF-beta were determined in the serum and
      the supernatant of ConA-stimulated CD4(+) lymphocytes. In AD patients the
      percentage of CD4(+)CD25(high)FoxP3(+) as well as CD3(+)CD8(+) cells increased,
      which positively correlated with SCORAD index (r = 0.55, p = 0.03). The
      concentrations of IL-10 in the CD4(+) lymphocyte culture supernatants and the
      concentrations of TGF-beta in the sera and the supernatant negatively correlated
      with the severity of AD (p < 0.01, r = -0.63; p < 0.02, r = -0.64 and p < 0.03, r
      = -0.58, respectively), whereas the serum concentration of IL-6 correlated
      positively (p < 0.003, r = 0.71). The regulatory cells expressed more CD62L and
      CD134 surface markers but less CD95. Reduced expression of the apoptotic CD95
      receptor suggests that survival time of these cells is prolonged. Since CD62L and
      CD134 were upregulated, the enhanced modulatory effect of
      CD4(+)CD25(high)FoxP3(+) cells seemed to be suggested, which may result in
      increased co-expression of CD28/CD152 on both CD4(+) and CD8(+) subpopulations.

PMID- 22968403
TI  - Comparing new onset heart failure with reduced ejection fraction and new onset
      heart failure with preserved ejection fraction: an epidemiologic perspective.
AB  - The incidence and prevalence of heart failure is increasing, especially heart
      failure with preserved ejection fraction (HFpEF) relative to heart failure with
      reduced ejection fraction (HFrEF). For both HFrEF and HFpEF, there is need to
      shift our focus from secondary to primary prevention. Detailed epidemiologic data
      on both HFpEF and HFrEF are needed to allow early identification of at-risk
      subjects. Current cohorts with new onset heart failure lack uniformity with
      respect to diagnosis, follow-up, and population characteristics, but most
      important, fail to distinguish between HFpEF and HFrEF. Studies on prevalent
      heart failure show ischemic heart disease as the predominant risk factor for
      HFrEF, while hypertension, atrial fibrillation, and diabetes are risk factors for
      HFpEF. As it becomes increasingly clear that both subtypes of heart failure are
      different syndromes, new cohorts and trials are necessary to obtain separate data
      on both subtypes of heart failure.

PMID- 22968405
TI  - Floral rewards in the tribe Sisyrinchieae (Iridaceae): oil as an alternative to
      pollen and nectar?
AB  - Iridaceae is one of the few families in which floral oils are produced and
      collected by pollinators as a resource. Perigonal nectaries and trichomal
      elaiophores are highly unusual within the tribe Sisyrinchieae. Both structures
      occur mainly on the staminal column, while they are usually distributed on the
      tepals in the other tribes of the subfamily Iridoideae. Sisyrinchieae is the
      largest tribe of Iridaceae present on the American continent, and the diversity
      observed may be related to the exceptional development of trichomal elaiophores
      within the genus Sisyrinchium, but knowledge concerning the other types of
      nuptial glandular structures within the tribe is still limited, preventing us
      from estimating their implication for species diversity. Structural observations
      and histochemical tests were performed to identify and characterize glandular
      structures and pollen rewards within the flowers of the genera Orthrosanthus,
      Sisyrinchium and Solenomelus. Perigonal nectaries were detected only in
      Solenomelus segethi, and trichomal elaiophores were characterized only within
      Sisyrinchium. All species showed large amounts of additional resources available
      for pollinators in the form of pollenkitt and polysaccharides present in the
      cytoplasm of the pollen grains. The results are discussed in a phylogenetic
      context, with regard to pollinators and floral rewards reported for the tribe
      Sisyrinchieae.

PMID- 22968404
TI  - Alterations in mitochondrial function in cardiac hypertrophy and heart failure.
AB  - Normal cardiac function requires high and continuous supply with ATP. As
      mitochondria are the major source of ATP production, it is apparent that
      mitochondrial function and cardiac function need to be closely related to each
      other. When subjected to overload, the heart hypertrophies. Initially, the
      development of hypertrophy is a compensatory mechanism, and contractile function
      is maintained. However, when the heart is excessively and/or persistently
      stressed, cardiac function may deteriorate, leading to the onset of heart
      failure. There is considerable evidence that alterations in mitochondrial
      function are involved in the decompensation of cardiac hypertrophy. Here, we
      review metabolic changes occurring at the mitochondrial level during the
      development of cardiac hypertrophy and the transition to heart failure. We will
      focus on changes in mitochondrial substrate metabolism, the electron transport
      chain and the role of oxidative stress. We will demonstrate that, with respect to
      mitochondrial adaptations, a clear distinction between hypertrophy and heart
      failure cannot be made because most of the findings present in overt heart
      failure can already be found in the various stages of hypertrophy.

PMID- 22968407
TI  - Lactobacillus species causing obesity in humans: where is the evidence?
AB  - By definition, probiotics are to provide health benefits and are expected not to
      cause any adverse effects in the general population. Recently, it has been
      suggested that probiotics and in particular lactobacilli are contributing to
      human obesity. Here, we critically review the data available on this topic. The
      main misconception in this hypothesis is that growth in livestock and children
      equals with obesity in adults. The former two are expected to grow and probiotics
      may, by reducing disease risk, contribute to an improved growth. It is not
      correct to extrapolate this growth (of all tissues) to body weight gain (growth
      of adipose tissue) in adults. Furthermore, when looking at animal models of
      obesity, it even appears the lactobacilli may potentially contribute to a
      reduction in body weight. Epidemiological studies lend strength to this. We
      therefore conclude that there is no evidence that consumption of lactobacilli or
      probiotics in general would contribute to obesity in humans.

PMID- 22968406
TI  - Comparative proteomic analyses reveal the changes of metabolic features in
      soybean (Glycine max) pistils upon pollination.
AB  - Siphonogamy is a critical process in plant reproductive growth, during which
      numerous cell-cell interaction events occur between pistil and pollen. Previous
      studies in Solanaceae, Papaveraceae, and Brassicaceae focusing on pollen-stigma
      recognition in self-incompatible systems have provided many important views. In
      this study, we profiled the proteome in soybean mature pistils before and after
      pollination. Comparative analyses of two-dimensional gel electrophoresis maps
      from un-pollinated and pollinated pistils were conducted. The results showed that
      22 proteins were increased and 36 proteins decreased after pollination.
      Functional categorization showed that most of them were metabolism- and redox
      related proteins. The enhancement of primary metabolism, biosynthesis of pollen
      tube guidance compounds, and adjustment of redox homeostasis system might be
      helpful for a successful pollination. Quantitative reverse transcript-polymerase
      chain reaction analysis implied that the regulation of gene expression might
      happen at both transcriptional and posttranscriptional levels during pollination.
      This study will enhance our understanding of pollen-stigma interaction in plant
      sexual reproductive growth.

PMID- 22968408
TI  - Protection of probiotic bacteria in a synbiotic matrix following aerobic storage
      at 4  degrees C.
AB  - The survival of single strains of Bifidobacterium breve, Bifidobacterium longum,
      Lactobacillus acidophilus, and Lactobacillus reuteri was investigated in
      synbiotics that included 10 mg/ml of fructo-oligosaccharides, inulin and pectic
      oligosaccharides in an alginate matrix under refrigerated (4  degrees C) aerobic
      storage conditions. When the matrices were cross-linked with calcium (45 mM), 102
      103 cfu/ml of L. acidophilus and L. reuteri, and 0-103 cfu/ml of B. breve and B.
      longum survived refrigerated aerobic storage for 28 days. Following refrigerated
      storage, acetic (3-9 mM), butyric (0-2 mM), propionic (5-16 mM) and lactic acids
      (1-48 mM) were produced during the growth of probiotics in BHI broth at 37 
      degrees C, suggesting their metabolic activity after storage was stressed. When
      calcium cross-linking was not used in synbiotics, the matrix remained more gel
      like after inoculation when compared to the calcium cross-linked matrix. At least
      107 cfu/ml of probiotic bacteria survived after 21 days of storage within these
      gel-like alginate matrices. Significantly higher levels of B. breve, L.
      acidophilus and L. reuteri were obtained from the synbiotic matrices supplemented
      with fructo-oligosaccharides, inulin and pectic-oligosaccharides compared to
      alginate alone. B. longum survival was the same (~7 logs) in all gel-like
      synbiotic matrices. These results show that synbiotics protected probiotic
      bacteria and extended their shelf-life under refrigerated aerobic conditions.
      Synbiotics represent a viable delivery vehicle for health-promoting bacteria.

PMID- 22968409
TI  - Differential cytokine expression in T-cell subsets of chicken caecal tonsils co
      cultured with three species of Lactobacillus.
AB  - Members of the intestinal microbiota play an important role in the development of
      T-cells. Little is known about responses of intestinal T-cell subsets of chickens
      to commensal bacteria. Therefore, we set out to characterise cytokine responses
      in T-cells after exposure to lactobacilli. Caecal tonsil mononuclear cells were
      isolated and co-cultured with Lactobacillus acidophilus, Lactobacillus reuteri
      and Lactobacillus salivarius for 12 hours. Subsequently the CD4+ and CD8+ cells
      were fractionated by flow cytometry and the expression of pro- and anti
      inflammatory cytokines as well as Toll-like receptor 21 (TLR21) was determined.
      The results demonstrated that chicken CD4+ and CD8+ T-cells express TLR21 and
      that the various isolates of lactobacilli differentially induces the expression
      of interleukin 10, interferon-gamma and transforming growth factor beta. Our
      results demonstrate that different Lactobacillus species have the capacity to
      regulate intestinal T-cell responses and that these responses may be important to
      intestinal homeostasis.

PMID- 22968410
TI  - Growth advantage of Streptococcus thermophilus over Lactobacillus bulgaricus in
      vitro and in the gastrointestinal tract of gnotobiotic rats.
AB  - The yoghurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii
      ssp. bulgaricus, are alleged to have beneficial effects on human health. The
      objective of this study was to characterise growth, biochemical activity and
      competitive behaviour of these two bacteria in vitro and in vivo. S. thermophilus
      LMD-9 and L. bulgaricus ATCC 11842 growth and lactate production were monitored
      in different media and in the gastrointestinal tract (GIT) of germ-free rats. In
      vitro, particularly in milk, S. thermophilus had a selective growth advantage
      over L. bulgaricus. The GIT of germ-free rats not supplemented with lactose was
      colonised by S. thermophilus but not by L. bulgaricus. Both bacteria were able to
      colonise the GIT of germ-free rats supplemented with 45 g/l lactose in their
      drinking water. However, if germ-free rats were inoculated with a mixture of the
      two bacteria and were supplemented with lactose, S. thermophilus rapidly and
      extensively colonised the GIT (1010 cfu/g faeces) at the expense of L.
      bulgaricus, which remained in most cases at levels <102 cfu/g faeces. S.
      thermophilus specifically produced L-lactate, while L. bulgaricus produced only D
      lactate, both in vitro and in vivo. S. thermophilus showed competitive and growth
      advantage over L. bulgaricus in vitro as well as in vivo in the GIT of germ-free
      rats and, accordingly, L-lactate was the main lactate isomer produced.

PMID- 22968411
TI  - Dietary sugar utilisation by putative oral probiotics.
AB  - Probiotic consumption and repeated probiotic intake have shown promising results
      as adjunct therapies in prevention and alleviation of some chronic disease
      conditions in the gastrointestinal tract. Recent evidence suggests that
      probiotics may also be beneficial in preventing oral diseases. An efficient
      probiotic candidate in the mouth, however, should not impose any risk to oral
      tissues, such as acid demineralisation of tooth enamel because of sugar
      fermentation. The aim of the present in vitro study was to evaluate the
      utilisation of some sugars and sugar alcohols by yogurt starter Lactobacillus
      delbrueckii subsp. bulgaricus strains and to assess the influence of these
      carbohydrate sources on cell surface properties. For comparsion, a commercially
      available probiotic, Lactobacillus rhamnosus GG, was used. The results showed
      that lactose, glucose and fructose were readily metabolised by all strains
      tested. However, strain-specific metabolic patterns were observed when other
      sugars and sugar alcohols were used as sole carbohydrate source in the growth
      medium. Surface properties of the bacteria such as hydrophobicity and surface
      associated proteins appeared to vary with the carbohydrate content of the growth
      medium. Based on these results it can be concluded that among the L. delbrueckii
      subsp. bulgaricus strains probiotic candidate strains are available that warrant
      further studies due to their inability to ferment sugars with pronounced
      cariogenic properties.

PMID- 22968412
TI  - Influence of Bacillus subtilis C-3102 on microbiota in a dynamic in vitro model
      of the gastrointestinal tract simulating human conditions.
AB  - Survival and germination rate of Bacillus subtilis C-3102 spores were
      investigated in a stomach and small intestine model (TIM-1), while the impact of
      C-3102 cells that had passed through TIM-1 on human colon microbiota was
      evaluated in a model of the large intestine (TIM-2). The survival of C-3102
      spores in TIM-1 was 99%; 8% of the spores had germinated. Effluent of TIM-1 was
      subsequently introduced into TIM-2 and a micro-array platform was employed to
      assess changes in the microbiota composition. The effluent, which contained
      germinated C-3102 cells, increased some Bifidobacterium species and decreased
      some Clostridium groups. These changes were greater compared to those obtained by
      adding C-3102 spores directly to TIM-2. The present study suggests that oral
      doses of B. subtilis C-3102 spores have the potential to modulate the human colon
      microbiota. This effect may be caused by germination of the spores in the
      gastrointestinal tract.

PMID- 22968413
TI  - Effect of pre- and probiotics on liver regeneration after resection: a
      randomised, double-blind pilot study.
AB  - Liver regeneration is a prerequisite for extended liver surgery. Several studies
      have shown that the bacterial gut flora is able to modulate liver function.
      Previously we observed that synbiotics could partly reverse the impaired mitosis
      rate of hepatocytes in a rat model of synchronous liver resection and colon
      anastomosis. The effect of synbiotics on liver function after hepatic resection
      has not been analysed yet. A prospective randomised double-blind pilot trial was
      undertaken in 19 patients scheduled for right hepatectomy. All patients received
      enteral nutrition immediately post-operatively. Comparison was made between a
      group receiving a combination of four probiotics and four fibres and a placebo
      group receiving the fibres only starting the day before surgery and continuing
      for 10 days. Primary study endpoint was the liver function capacity measured by
      13C-methacetin breath test and indocyanine green plasma disappearance rate.
      Portal vein flow, liver volumetry, laboratory parameters for liver function,
      length of hospital stay, post-operative complications and side effects of
      synbiotic therapy were recorded. Liver function capacity was comparable in both
      groups. Complications had a negative impact on liver function. Because
      complications were more severe in the verum group, a sub-analysis was performed.
      In case of an uncomplicated course, liver function capacity was better in the
      patients with synbiotics. No severe side effects occurred. Synbiotics might be
      able to increase liver function capacity in patients after liver resection, but
      patient numbers were too small and the clinical courses too heterogeneous to draw
      any definite conclusions.

PMID- 22968415
TI  - Frequency and consequences of violence in community pharmacies in Ireland.
AB  - BACKGROUND: Violence in community pharmacies in Ireland is thought to be common
      but underreported. The frequency and consequences of violence has not been
      studied previously. AIMS: To establish the frequency and nature of violence in
      community pharmacies over 12 months, and to investigate the impact of violence on
      employees and possible consequence for the industry. METHODS: A two-part survey
      was distributed to community pharmacies in Ireland in 2011 (n = 200). The first
      part related to pharmacy demographics, the frequency of various violent events
      (verbal abuse, threats etc.), the respondents' worry regarding violence and its
      impact on their co-workers. The second part concerned individual employees'
      subjective response to a violent event, using the Impact of Event Scale-Revised
      (IES-R). RESULTS: Fifty-seven per cent of the pharmacies responded, with 77%
      reporting some violent event (verbal or physical), over the past year. Eighteen
      per cent reported physical assault, and 63% were worried about workplace
      violence. There was no association between late night opening hours or pharmacy
      size and violence frequency. Positive statistically significant correlations were
      present between all types of violence and absenteeism and employee fear levels.
      An IES-R score could be calculated for 75 respondents; the median IES-R score was
      8 with 19% reporting clinically significant scores. CONCLUSIONS: Violence is
      common in Irish community pharmacies and impacts on employees and the industry.

PMID- 22968417
TI  - How are small endohedral silicon clusters stabilized?
AB  - Clusters in the (Be, B, C)@Si(n)((0,1,2+)) (n = 6-10) series, isoelectronic to
      Si(n)(2-), present multiple symmetric structures, including rings, cages and open
      structures, which the doping atom stabilizes using contrasting bonding
      mechanisms. The most striking feature of these clusters is the absence of
      electron transfer (for Be) or even the inversion (for B and C) in comparison to
      classic endohedral metallofullerenes (e.g. from the outer frameworks towards the
      enclosed atom). The relatively small cavity of the highly symmetric Si(8) cubic
      cage benefits more strongly from the encapsulation of a boron atom than from the
      insertion of a too large beryllium atom. Overall, the maximization of multicenter
      type bonding, as visualized by the Localized Orbital Locator (LOL), is the key to
      the stabilization of the small Si(n) cages. Boron offers the best balance between
      size, electronegativity and delocalized bonding pattern when compared to
      beryllium and carbon.

PMID- 22968416
TI  - Spatiotemporally controlled delivery of soluble factors for stem cell
      differentiation.
AB  - Despite the fact that cells in vivo are largely affected by the spatial
      heterogeneity in their surroundings, in vitro experimental procedures for stem
      cell differentiation have been relying on spatially uniform culture environments
      so far. Here, we present a method to form spatiotemporally non-uniform culture
      environments for stem cell differentiation using a membrane-based microfluidic
      device. By adopting a porous membrane with relatively large pores, patterned
      delivery of soluble factors is maintained stably over a period of time long
      enough for cell differentiation. We report that spatial patterns of mouse induced
      pluripotent stem cells (miPSCs) differentiation can be controlled by the present
      method. Furthermore, it is shown that the cell fate decision of miPSCs is
      determined by time-dependent switching of the delivery pattern. The present
      technique could be of relevance to the detailed analyses of the characteristics
      of stem cell differentiation in time and space, opening up a new insight into
      regenerative biology.

PMID- 22968418
TI  - Colorimetric detection of single-nucleotide polymorphisms with a real-time PCR
      like sensitivity.
AB  - Coupling gold nanoparticle-based ligation to a ligation chain reaction enables
      colorimetric detection of single-nucleotide polymorphisms with a real-time PCR
      like sensitivity. One mutant in 2000 copies of a wild-type gene can be detected
      in 20-100 pg of PCR-amplified genomic DNA samples.

PMID- 22968419
TI  - High-throughput secondary screening at the single-cell level.
AB  - We have developed an automated system for drug screening using a single-cell
      multiple functional response technology. The approach uses a semiautomated
      preparatory system, high-speed sample collection, and a unique analytical tool
      that provides instantaneous results for compound dilutions using 384-well plates.
      The combination of automation and rapid robotic sampling increases quality
      control and robustness. High-speed flow cytometry is used to collect single-cell
      results together with a newly defined analytical tool for extraction of IC(50)
      curves for multiple assays per cell. The principal advantage is the extreme speed
      of sample collection, with results from a 384-well plate being completed for both
      collection and data processing in less than 10 min. Using this approach, it is
      possible to extract detailed drug response information in a highly controlled
      fashion. The data are based on single-cell results, not populations. With
      simultaneous assays for different functions, it is possible to gain a more
      detailed understanding of each drug/compound interaction. Combined with
      integrated advanced data processing directly from raw data files, the process
      from sampling to analytical results is highly intuitive. Direct PubMed links
      allow review of drug structure and comparisons with similar compounds.

PMID- 22968420
TI  - Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human
      papillomavirus-associated genital-tumor regression in mice.
AB  - Human papillomaviruses (HPV)-related cervical cancer is the second leading cause
      of cancer death in women worldwide. Despite active development, HPV E6/E7
      oncogene-specific therapeutic vaccines have had limited clinical efficacy to
      date. Here, we report that intravaginal (IVAG) instillation of CpG-ODN (TLR9
      agonist) or poly-(I:C) (TLR3 agonist) after subcutaneous E7 vaccination increased
      ~fivefold the number of vaccine-specific interferon-gamma-secreting CD8 T cells
      in the genital mucosa (GM) of mice, without affecting the E7-specific systemic
      response. The IVAG treatment locally increased both E7-specific and total CD8 T
      cells, but not CD4 T cells. This previously unreported selective recruitment of
      CD8 T cells from the periphery by IVAG CpG-ODN or poly-(I:C) was mediated by TLR9
      and TLR3/melanoma differentiation-associated gene 5 signaling pathways,
      respectively. For CpG, this recruitment was associated with a higher proportion
      of GM-localized CD8 T cells expressing both CCR5 and CXCR3 chemokine receptors
      and E-selectin ligands. Most interestingly, IVAG CpG-ODN following vaccination
      led to complete regression of large genital HPV tumors in 75% of mice, instead of
      20% with vaccination alone. These findings suggest that mucosal application of
      immunostimulatory molecules might substantially increase the effectiveness of
      parenterally administered vaccines.

PMID- 22968421
TI  - Myeloid hypoxia-inducible factor 1alpha prevents airway allergy in mice through
      macrophage-mediated immunoregulation.
AB  - Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory
      and bactericidal functions in myeloid cells. Conditional genetic ablation of its
      major subunit Hif1alpha in the myeloid lineage consequently results in decreased
      inflammatory responses in classical models of acute inflammation in mice. By
      contrast, we report here that mice conditionally deficient for Hif1alpha in
      myeloid cells display enhanced sensitivity to the development of airway allergy
      to experimental allergens and house-dust mite antigens. We support that upon
      allergen exposure, MyD88-dependent upregulation of Hif1alpha boosts the
      expression of the immunosuppressive cytokine interleukin (IL)-10 by lung
      interstitial macrophages (IMs). Hif1alpha-dependent IL-10 secretion is required
      for IMs to block allergen-induced dendritic cell activation and consequently for
      preventing the development of allergen-specific T-helper cell responses upon
      allergen exposure. Thus, this study supports that, in addition to its known pro
      inflammatory activities, myeloid Hif1alpha possesses immunoregulatory functions
      implicated in the prevention of airway allergy.

PMID- 22968423
TI  - [Demands on dialysis access from the nephrologists point of view].
AB  - Vascular access is the lifeline of hemodialysis patients. The superiority of
      autogenous arteriovenous fistulas compared to prostethic arteriovenous grafts or
      a central venous catheter is well established. Fistulas have a far lower risk of
      failure and a reduced requirement for revision compared to prosthetic grafts.
      Alternative vascular access can be achieved via a prosthetic graft or permanent
      central venous catheter but the risk of infection is increased. The most
      important complications are shunt thrombosis, stenosis, aneurysms or steal
      syndrome. Signs of these complications should be recognized by the dialysis team
      and early surgical intervention can avoid major complications. In many cases a
      complex shunt is necessary if the patient has been on dialysis for a long time.
      Interaction between the dialysis team, nephrologists, surgeons and interventional
      radiologists can improve the prognosis of dialysis patient.

PMID- 22968422
TI  - A bacterial glycan core linked to surface (S)-layer proteins modulates host
      immunity through Th17 suppression.
AB  - Tannerella forsythia is a pathogen implicated in periodontitis, an inflammatory
      disease of the tooth-supporting tissues often leading to tooth loss. This key
      periodontal pathogen is decorated with a unique glycan core O-glycosidically
      linked to the bacterium's proteinaceous surface (S)-layer lattice and other
      glycoproteins. Herein, we show that the terminal motif of this glycan core acts
      to modulate dendritic cell effector functions to suppress T-helper (Th)17
      responses. In contrast to the wild-type bacterial strain, infection with a mutant
      strain lacking the complete S-layer glycan core induced robust Th17 and reduced
      periodontal bone loss in mice. Our findings demonstrate that surface
      glycosylation of this pathogen may act to ensure its persistence in the host
      likely through suppression of Th17 responses. In addition, our data suggest that
      the bacterium then induces the Toll-like receptor 2-Th2 inflammatory axis that
      has previously been shown to cause bone destruction. Our study provides a
      biological basis for pathogenesis and opens opportunities in exploiting bacterial
      glycans as therapeutic targets against periodontitis and a range of other
      infectious diseases.

PMID- 22968424
TI  - [Rejection of unilateral parathyroidectomy for primary hyperparathyroidism?].

PMID- 22968426
TI  - Influence of the individual DPOAE growth behavior on DPOAE level variations
      caused by conductive hearing loss and elevated intracranial pressure.
AB  - OBJECTIVES: Minor conductive hearing loss (CHL) can compromise the evaluation of
      the inner ear function with distortion product otoacoustic emissions (DPOAE).
      Elevation of the intracranial pressure (ICP) is also expected to alter the middle
      ear (ME) sound transmission. An impaired ME sound transmission leads to an
      attenuation of the DPOAE primary tone levels (L1 and L2) during forward
      transmission and of DPOAE levels (LDP) during backward transmission. The effect
      of the attenuation of L1 and L2 is complex and might have unexpected effects on
      DPOAE levels. In this work, CHL- and ICP-induced alterations of LDP versus L1
      growth functions (constant L2 and increasing L1) are investigated. The first aim
      of this study is to explain how alterations of ME sound transmission can affect
      DPOAEs and to characterize the dependency of DPOAE level alterations on L2,L1
      combinations and on the individual shape of LDP versus L1 growth functions. The
      second aim is to identify analogies between CHL- and ICP-induced alterations of
      DPOAEs and to discuss implications for a potential noninvasive ICP monitoring.
      DESIGN: This study focuses on general theoretical considerations, supported by
      selected experimental observations in different species and simulations. DPOAEs
      were measured in guinea pigs before and after induction of a CHL (1 ear) and
      during increased ICP (1 ear), and in humans during changes of the postural
      position to alter the ICP (4 ears). RESULTS: In both CHL and elevated ICP, DPOAE
      levels are not only reduced, but LDP versus L1 growth functions exhibit a shift
      to higher L1. The absolute DPOAE level alterations strongly depend on the L2,L1
      combinations and the individual shape of the LDP versus L1 growth functions. In
      steeper LDP versus L1 growth functions, the DPOAE level alterations exhibit a
      larger variation. DPOAE levels can even increase. The largest variation can be
      found in ears with a nonmonotonic DPOAE growth behavior. An example of a guinea
      pig ear is presented with a nonmonotonic DPOAE growth behavior and a CHL of 4 dB,
      where the DPOAE level alterations varied between -32 and +9 dB depending on L1.
      CONCLUSIONS: The data enable a more comprehensive view of DPOAE level alterations
      during CHL and elevated ICP. The observations also explain the problem that DPOAE
      and ICP alterations do not correlate linearly. An evaluation of the shift of the
      LDP versus L1 growth function along the L1 axis provides a potential tool to
      improve both the assessment of the inner ear function in the presence of a CHL
      and noninvasive ICP monitoring with DPOAEs.

PMID- 22968425
TI  - [Keloid and hypertrophic scar treatment modalities. An update].
AB  - Over the past two decades the treatment of hypertrophic scars and keloids has
      seen substantial changes due to the evolution of current and establishment of new
      conservative and surgical methods. This review gives an overview of the current
      research with respect to the multifactorial etiology and pathophysiology of
      keloids and hypertrophic scars, discusses conservative surgical treatment options
      and provides an outlook on novel treatment strategies.

PMID- 22968428
TI  - Low cellular P-quota and poor metabolic adaptations of the freshwater
      cyanobacterium Anabaena fertilissima Rao during Pi-limitation.
AB  - Anabaena fertilissima is a filamentous freshwater N(2)-fixing cyanobacterium,
      isolated from a paddy field. Growth of the cyanobacterium was limited by the non
      availability of inorganic phosphate (Pi) in the growth medium and was found to be
      directly related to the cellular P quota, which declined rapidly in Pi-deficient
      cells. To overcome Pi-deficiency, cells induced both cell-bound and cell-free
      alkaline phosphatase activities (APase). The activity of cell-bound APase was
      rapid and 5-6 times higher than that of the cell-free APase activity. Native gel
      electrophoresis revealed the presence of two APase activity bands for both the
      cell bound and cell-free APase (Mr ~42 and 34 kDa). For Pi-deficient cells, APase
      activity was inversely related to cellular P-quota. In A. fertilissima phosphate
      uptake was facilitated by single high-affinity phosphate transporter (K ( s ),
      4.54 MUM; V(max), 4.84 MUmol mg protein(-1) min(-1)). Pi-deficiency severely
      reduced the photosynthetic rate, respiration rate and nitrate uptake, as well as
      the activities of nitrate reductase, nitrite reductase and nitrogenase enzymes.
      In photosynthesis, PSII activity was maximally inhibited, followed by PSI and
      whole chain activities. Transcript levels of five key glycolytic enzymes showed
      the poor adaptability of the cyanobacterium to switch its metabolic activity to
      PPi-dependent enzyme variants, which has rather constant cellular concentrations.

PMID- 22968427
TI  - Binaural benefit with and without a bilateral spectral mismatch in acoustic
      simulations of cochlear implant processing.
AB  - OBJECTIVES: This study investigated whether a spectral mismatch across ears
      influences the benefit of redundancy, squelch, and head shadow differently in
      speech perception using acoustic simulation of bilateral cochlear implant (CI)
      processing. DESIGN: Ten normal-hearing subjects participated in the study, and
      acoustic simulations of CIs were used to test these subjects. Sentence
      recognition, presented unilaterally and bilaterally, was measured at +5 dB and
      +10 dB signal-to-noise ratios (SNRs) with bilaterally matched and mismatched
      conditions. Unilateral and bilateral CIs were simulated using 8-channel sine wave
      vocoders. Binaural spectral mismatch was introduced by changing the relative
      simulated insertion depths across ears. Subjects were tested while listening with
      headphones; head-related transfer functions were applied before the vocoder
      processing to preserve natural interaural level and time differences. RESULTS:
      For both SNRs, greater and more consistent binaural benefit of squelch and
      redundancy occurred for the matched condition whereas binaural interference of
      squelch and redundancy occurred for the mismatched condition. However,
      significant binaural benefit of head shadow existed irrespective of spectral
      mismatches and SNRs. CONCLUSIONS: The results suggest that bilateral spectral
      mismatch may have a negative impact on the binaural benefit of squelch and
      redundancy for bilateral CI users. The results also suggest that clinical mapping
      should be carefully administrated for bilateral CI users to minimize the
      difference in spectral patterns between the two CIs.

PMID- 22968429
TI  - Vascular pancreatic lesions: spectrum of imaging findings of malignant masses and
      mimics with pathologic correlation.
AB  - The differential diagnosis of hypervascular pancreatic lesions is complex, and
      includes endocrine and exocrine tumors of the pancreas, metastases to the
      pancreas, and masses, or mass-like lesions, arising from the neurovascular
      networks traversing the pancreas. In this manuscript, we will discuss salient
      imaging findings of these masses, pertinent differential diagnoses, as well as
      review clinical symptomatology that may aid in the diagnosis of some of these
      lesions. 

PMID- 22968430
TI  - miRNA-218 contributes to the regulation of D-glucuronyl C5-epimerase expression
      in normal and tumor breast tissues.
AB  - microRNAs (miRNAs) are key posttranscriptional regulators of gene expression. In
      the present study, regulation of tumor-suppressor gene D-glucuronyl C5-epimerase
      (GLCE) by miRNA-218 was investigated. Significant downregulation of miRNA-218
      expression was shown in primary breast tumors. Exogenous miRNA-218/anti-miRNA-218
      did not affect GLCE mRNA but regulated GLCE protein level in MCF7 breast
      carcinoma cells in vitro. Comparative analysis showed a positive correlation
      between miRNA-218 and GLCE mRNA, and negative correlation between miRNA-218 and
      GLCE protein levels in breast tissues and primary tumors in vivo, supporting a
      direct involvement of miRNA-218 in posttranscriptional regulation of GLCE in
      human breast tissue. A common scheme for the regulation of GLCE expression in
      normal and tumor breast tissues is suggested.

PMID- 22968432
TI  - Housing status and the health of people living with HIV/AIDS.
AB  - Individuals who are homeless or living in marginal conditions have an elevated
      burden of infection with HIV. Existing research suggests the HIV/AIDS pandemic in
      resource-rich settings is increasingly concentrated among members of vulnerable
      and marginalized populations, including homeless/marginally-housed individuals,
      who have yet to benefit fully from recent advances in highly-active
      antiretroviral therapy (HAART). We reviewed the scientific evidence investigating
      the relationships between inferior housing and the health status, HAART access
      and adherence and HIV treatment outcomes of people living with HIV/AIDS (PLWHA.)
      Studies indicate being homeless/marginally-housed is common among PLWHA and
      associated with poorer levels of HAART access and sub-optimal treatment outcomes.
      Among homeless/marginally-housed PLWHA, determinants of poorer HAART
      access/adherence or treatment outcomes include depression, illicit drug use, and
      medication insurance status. Future research should consider possible social- and
      structural-level determinants of HAART access and HV treatment outcomes that have
      been shown to increase vulnerability to HIV infection among homeless/marginally
      housed individuals. As evidence indicates homeless/marginally-housed PLWHA with
      adequate levels of adherence can benefit from HAART at similar rates to housed
      PLWHA, and given the individual and community benefits of expanding HAART use,
      interventions to identify HIV-seropositive homeless/marginally-housed
      individuals, and engage them in HIV care including comprehensive support for
      HAART adherence are urgently needed.

PMID- 22968431
TI  - Limited contribution of common genetic variants to risk for liver injury due to a
      variety of drugs.
AB  - BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a serious adverse drug
      event that is suspected to have a heritable component. We carried out a genome
      wide association study of 783 individuals of European ancestry who experienced
      DILI due to more than 200 implicated drugs. METHODS: DILI patients from the US
      based Drug-Induced Liver Injury Network (n=401) and three international
      registries (n=382) were genotyped with the Illumina 1Mduo BeadChip and compared
      with population controls (n=3001). Potential associations were tested in 307
      independent Drug-Induced Liver Injury Network cases. RESULTS: After accounting
      for known major histocompatibility complex risk alleles for flucloxacillin-DILI
      and amoxicillin/clavulanate-DILI, there were no genome-wide significant
      associations, including in the major histocompatibility complex region.
      Stratification of DILI cases according to clinical phenotypes (injury type,
      latency, age of onset) also did not show significant associations. An analysis of
      hepatocellular DILI (n=285) restricted to 193 single-nucleotide polymorphisms
      previously associated with autoimmune disease showed a trend association for
      rs7574865, in the vicinity of signal transducer and activator of transcription 4
      (STAT4) (P=4.5*10(-4)). This association was replicated in an independent cohort
      of 168 hepatocellular DILI cases (P=0.011 and 1.5*10(-5) for combined cohorts).
      No significant associations were found with stratification by other clinical or
      demographic variables. CONCLUSION: Although not significant at the genome-wide
      level, the association between hepatocellular DILI and STAT4 is consistent with
      the emerging role of the immune system in DILI. However, the lack of genome-wide
      association study findings supports the idea that strong genetic determinants of
      DILI may be largely drug-specific or may reflect rare genetic variations, which
      were not assessed in our study.

PMID- 22968433
TI  - Stevioside protects LPS-induced acute lung injury in mice.
AB  - Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known
      to exhibit anti-inflammatory properties. To evaluate the effect and the possible
      mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury,
      male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before
      intranasal instillation of LPS. Seven hours later, tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were
      measured by using enzyme-linked immunosorbent assay. The number of total cells,
      neutrophils, and macrophages in the BALF were also determined. The right lung was
      excised for histological examination and analysis of myeloperoxidase activity and
      nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS),
      nuclear factor-kappa B (NF-kappaB), inhibitory kappa B protein were detected by
      western blot. The results showed that stevioside markedly attenuated the LPS
      induced histological alterations in the lung. Stevioside inhibited the production
      of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by
      LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue
      significantly decreased, the number of total cells, neutrophils, and macrophages
      in the BALF were also significantly reduced after treatment with stevioside.
      Moreover, western blotting showed that stevioside inhibited the phosphorylation
      of IkappaB-alpha and NF-kappaB caused by LPS. Taken together, our results suggest
      that anti-inflammatory effect of stevioside against the LPS-induced acute lung
      injury may be due to its ability of inhibition of the NF-kappaB signaling
      pathway. Stevioside may be a promising potential therapeutic reagent for acute
      lung injury treatment.

PMID- 22968435
TI  - The relationship between the location of thyroglossal duct cysts and the
      epithelial lining.
AB  - Thyroglossal duct cysts (TDCs) with ambiguous epithelial lining are the most
      common midline cervical anomaly encountered in children. To histopathologically
      study the epithelial lining of 32 thyroglossal duct cysts in relation to their
      locations. A total of 32 cases of thyroglossal duct cysts were collected for this
      study. The samples were classified into 3 groups as follows: (1) above the hyoid
      bone; (2) at the level of hyoid bone; (3) below the hyoid bone. All samples were
      H&E stained. Seventeen TDCs (53 %) were found above the hyoid bone, 6 (18.8 %)
      were found at the level of hyoid bone and 9 (28.1 %) were found below the hyoid
      bone. Of the 32 total cases, 6 (18.8 %) were lined with stratified squamous
      epithelium (SSE), 17 (53 %) were lined with pseudostratified ciliated epithelium
      (PSCE), 3 (9.4 %) were lined with stratified cuboidal epithelium (SCE), and 6
      (18.8 %) exhibited both SSE and PSCE. Pseudostratified ciliated epithelium was
      dominant in the region superior to the hyoid bone, whereas SCE was detected only
      in TDCs at the level of hyoid bone. These differences were statistically
      significant (P = 0.0001). Different types of epithelial lining were detected in
      the study samples of TDCs. A statistically significant correlation was found
      between the type of epithelium detected and the location of the TDC at the time
      of diagnosis.

PMID- 22968434
TI  - Human-specific CpG "beacons" identify loci associated with human-specific traits
      and disease.
AB  - Regulatory change has long been hypothesized to drive the delineation of the
      human phenotype from other closely related primates. Here we provide evidence
      that CpG dinucleotides play a special role in this process. CpGs enable epigenome
      variability via DNA methylation, and this epigenetic mark functions as a
      regulatory mechanism. Therefore, species-specific CpGs may influence species
      specific regulation. We report non-polymorphic species-specific CpG dinucleotides
      (termed "CpG beacons") as a distinct genomic feature associated with CpG island
      (CGI) evolution, human traits and disease. Using an inter-primate comparison, we
      identified 21 extreme CpG beacon clusters (>= 20/kb peaks, empirical p < 1.0 *
      10(-3)) in humans, which include associations with four monogenic developmental
      and neurological disease related genes (Benjamini-Hochberg corrected p = 6.03 *
      10(-3)). We also demonstrate that beacon-mediated CpG density gain in CGIs
      correlates with reduced methylation in these species in orthologous CGIs over
      time, via human, chimpanzee and macaque MeDIP-seq. Therefore mapping into both
      the genomic and epigenomic space the identified CpG beacon clusters define points
      of intersection where a substantial two-way interaction between genetic sequence
      and epigenetic state has occurred. Taken together, our data support a model for
      CpG beacons to contribute to CGI evolution from genesis to tissue-specific to
      constitutively active CGIs.

PMID- 22968436
TI  - Shifting the treatment model: impact on engagement in outpatient therapy.
AB  - Attrition in youth outpatient mental health clinics ranges from 30 to 70 % and
      often occurs early in treatment. We implemented specific treatment planning
      strategies designed to reduce early attrition. Following implementation, 14.3 %
      of clients dropped out during the first five sessions compared to 26.1 % in the
      historical control (p < 0.001). During treatment, 33.6 % of clients dropped out
      in the intervention compared to 55.5 % in the historical control (p < 0.001).
      Engagement is central to the therapeutic process and may be particularly relevant
      early in treatment. Implementing evidence-based strategies to promote a
      collaborative relationship between the family and the clinician may increase
      engagement and decrease attrition. 

PMID- 22968438
TI  - A low-cost, label-free DNA detection method in lab-on-chip format based on
      electrohydrodynamic instabilities, with application to long-range PCR.
AB  - In order to evolve from a "chip in the lab" to a "lab on a chip" paradigm, there
      is still a strong demand for low-cost, portable detection technologies, notably
      for analytes at low concentrations. Here we report a new label-free DNA detection
      method with direct electronic read, and apply it to long-range PCR. This method
      uses a nonlinear electrohydrodynamic phenomenon: when subjected to high electric
      fields (typically above 100 V cm(-1)), suspensions of large polyelectrolytes,
      such as long DNA molecules, create "giant" dynamic concentration fluctuations.
      These fluctuations are associated with large conductivity inhomogeneities, and we
      use here a contact-mode local conductivity detector to detect these fluctuations.
      In order to decouple the detection electronics from the high voltage excitation
      one, an original "doubly symmetric" floating mode battery-operated detection
      scheme was developed. A wavelet analysis was then applied, to unravel from the
      chaotic character of the electohydrodynamic instabilities a scalar signal
      robustly reflecting the amplification of DNA. As a first proof of concept, we
      measured the products of the off-chip amplification of 10 kbp DNA from lambda
      phage DNA, achieving a sensitivity better than 100 fg DNA in the original 50 MUl
      sample. This corresponds to the amplification products of less than 100 initial
      copies of target DNA. The companion enabling technologies developed to implement
      this new concept, i.e. the doubly symmetric contact conductivity detection and
      wavelet analysis, may also find various other applications in lab-on-chips.

PMID- 22968439
TI  - Respiratory viral infections in pediatric solid organ and hematopoietic stem cell
      transplantation.
AB  - Respiratory viruses are common in children, including pediatric recipients of
      both solid organ transplantation and hematopoietic stem cell transplantation. The
      prevalence and risk factors in each of these groups are reviewed. Furthermore,
      associated morbidity and mortality in pediatric transplant recipients with
      respiratory viral infections are addressed. The literature on specific prevention
      and treatment options for respiratory syncytial virus, adenovirus, influenza, and
      other respiratory viruses in pediatric solid organ and hematopoietic stem cell
      transplant recipients is reported.

PMID- 22968440
TI  - Single-bundle versus double-bundle anterior cruciate ligament reconstruction: an
      up-to-date meta-analysis.
AB  - PURPOSE: The aim of this meta-analysis was to compare the results of arthroscopic
      single-bundle and double-bundle anterior cruciate ligament (ACL) reconstruction.
      METHODS: We systematically searched electronic databases to identify randomised
      controlled trials (RCTs) in which arthroscopic single-bundle was compared with
      double-bundle for ACL reconstruction. The search strategy followed the
      requirements of the Cochrane Library Handbook. The outcomes of these studies were
      analysed in terms of graft failures, Lysholm score, negative pivot-shift test,
      KT1000 arthrometer measurements, knee extensor and flexor peak torques, knee
      extension and flexion deficit, and subjective and objective International Knee
      Documentation Committee (IKDC) final score. Methodological quality was assessed
      and data were extracted independently. Standard mean difference (SMD) or odds
      ratio (OR) with 95 % confidence interval (CI) was calculated by a fixed effects
      or random effects model. Heterogeneity across the studies was assessed with the I
      square and chi-square statistic. Forest plots were also generated. RESULTS: We
      identified 17 RCTs comprising 1,381 patients who were treated by arthroscopic
      single-bundle versus double-bundle ACL reconstruction. The results of meta
      analysis of these studies showed that arthroscopic double-bundle reconstruction
      was associated with a lower risk of graft failures (P=0.002) and a lower rate of
      positive pivot-shift test (P<0.0001). Compared with single-bundle reconstruction,
      double-bundle reconstruction had a lower KT1000 arthrometer measurement
      (P<0.00001), a lower knee extension deficit (P=0.006) and a higher subjective
      IKDC score (P=0.03). There was no statistically significant difference between
      single-bundle and double-bundle reconstruction in Lysholm score (P=0.91), knee
      extensor peak torques (P=0.97), knee flexor peak torques (P=0.96), knee flexion
      deficit (P=0.30) and objective IKDC score (P=0.18). CONCLUSIONS: Considering the
      more favourable outcomes of graft failures, knee joint stability and knee joint
      function in double-bundle reconstruction, we concluded that arthroscopic double
      bundle reconstruction should be considered as the primary treatment in ACL
      reconstruction.

PMID- 22968441
TI  - SH3GL2 is frequently deleted in non-small cell lung cancer and downregulates
      tumor growth by modulating EGFR signaling.
AB  - The purpose of this study was to identify key genetic pathways involved in non
      small cell lung cancer (NSCLC) and understand their role in tumor progression. We
      performed a genome wide scanning using paired tumors and corresponding 16 mucosal
      biopsies from four follow-up lung cancer patients on Affymetrix 250K-NSpI array
      platform. We found that a single gene SH3GL2 located on human chromosome 9p22 was
      most frequently deleted in all the tumors and corresponding mucosal biopsies. We
      further validated the alteration pattern of SH3GL2 in a substantial number of
      primary NSCLC tumors at DNA and protein level. We also overexpressed wild-type
      SH3GL2 in three NSCLC cell lines to understand its role in NSCLC progression.
      Validation in 116 primary NSCLC tumors confirmed frequent loss of heterozygosity
      of SH3GL2 in overall 51 % (49/97) of the informative cases. We found
      significantly low (p = 0.0015) SH3GL2 protein expression in 71 % (43/60) primary
      tumors. Forced overexpression of wild-type (wt) SH3GL2 in three NSCLC cell lines
      resulted in a marked reduction of active epidermal growth factor receptor (EGFR)
      expression and an increase in EGFR internalization and degradation. Significantly
      decreased in vitro (p = 0.0015-0.030) and in vivo (p = 0.016) cellular growth,
      invasion (p = 0.029-0.049), and colony formation (p = 0.023-0.039) were also
      evident in the wt-SH3GL2-transfected cells accompanied by markedly low expression
      of activated AKT(Ser(473)), STAT3 (Tyr(705)), and PI3K. Downregulation of SH3GL2
      interactor USP9X and activated beta-catenin was also evident in the SH3GL2
      transfected cells. Our results indicate that SH3GL2 is frequently deleted in
      NSCLC and regulates cellular growth and invasion by modulating EGFR function.

PMID- 22968442
TI  - Global analysis of genome, transcriptome and proteome reveals the response to
      aneuploidy in human cells.
AB  - Extra chromosome copies markedly alter the physiology of eukaryotic cells, but
      the underlying reasons are not well understood. We created human trisomic and
      tetrasomic cell lines and determined the quantitative changes in their
      transcriptome and proteome in comparison with their diploid counterparts. We
      found that whereas transcription levels reflect the chromosome copy number
      changes, the abundance of some proteins, such as subunits of protein complexes
      and protein kinases, is reduced toward diploid levels. Furthermore, using the
      quantitative data we investigated the changes of cellular pathways in response to
      aneuploidy. This analysis revealed specific and uniform alterations in pathway
      regulation in cells with extra chromosomes. For example, the DNA and RNA
      metabolism pathways were downregulated, whereas several pathways such as energy
      metabolism, membrane metabolism and lysosomal pathways were upregulated. In
      particular, we found that the p62-dependent selective autophagy is activated in
      the human trisomic and tetrasomic cells. Our data present the first broad
      proteomic analysis of human cells with abnormal karyotypes and suggest a uniform
      cellular response to the presence of an extra chromosome.

PMID- 22968443
TI  - A feel for systems.

PMID- 22968444
TI  - Gene location and DNA density determine transcription factor distributions in
      Escherichia coli.
AB  - The diffusion coefficient of the transcription factor LacI within living
      Escherichia coli has been measured directly by in vivo tracking to be D = 0.4
      MUm(2)/s. At this rate, simple models of diffusion lead to the expectation that
      LacI and other proteins will rapidly homogenize throughout the cell. Here, we
      test this expectation of spatial homogeneity by single-molecule visualization of
      LacI molecules non-specifically bound to DNA in fixed cells. Contrary to
      expectation, we find that the distribution depends on the spatial location of its
      encoding gene. We demonstrate that the spatial distribution of LacI is also
      determined by the local state of DNA compaction, and that E. coli can dynamically
      redistribute proteins by modifying the state of its nucleoid. Finally, we show
      that LacI inhomogeneity increases the strength with which targets located
      proximally to the LacI gene are regulated. We propose a model for intranucleoid
      diffusion that can reconcile these results with previous measurements of LacI
      diffusion, and we discuss the implications of these findings for gene regulation
      in bacteria and eukaryotes.

PMID- 22968446
TI  - The changing privacy landscape in the era of big data.

PMID- 22968445
TI  - Extensive quantitative remodeling of the proteome between normal colon tissue and
      adenocarcinoma.
AB  - We report a proteomic analysis of microdissected material from formalin-fixed and
      paraffin-embedded colorectal cancer, quantifying > 7500 proteins between patient
      matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels
      of 1808 proteins changed significantly between normal and cancer tissues, a much
      larger fraction than that reported in transcript-based studies. Tumor cells
      exhibit extensive alterations in the cell-surface and nuclear proteomes.
      Functionally similar changes in the proteome were observed comparing rapidly
      growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic
      remodeling between primary cancer and metastases, suggesting that no drastic
      proteome changes are necessary for the tumor to propagate in a different tissue
      context. Additionally, we introduce a new way to determine protein copy numbers
      per cell without protein standards. Copy numbers estimated in enterocytes and
      cancer cells are in good agreement with CaCo-2 and HeLa cells and with the
      literature data. Our proteomic data set furthermore allows mapping quantitative
      changes of functional protein classes, enabling novel insights into the biology
      of colon cancer.

PMID- 22968447
TI  - A ladder type iron(II) coordination polymer with cooperative spin transition.
AB  - Ladder type 1D coordination polymers were synthesised with the aim to improve the
      spin crossover properties of the iron(II) complexes following the concepts of
      crystal engineering. A wide hysteresis loop (34 K) was observed if rigid linkers
      were used. The first X-ray structure for a 1D iron(II) ladder is reported.

PMID- 22968448
TI  - Competing risks with missing covariates: effect of haplotypematch on
      hematopoietic cell transplant patients.
AB  - In this paper we consider a problem from hematopoietic cell transplant (HCT)
      studies where there is interest on assessing the effect of haplotype match for
      donor and patient on the cumulative incidence function for a right censored
      competing risks data. For the HCT study, donor's and patient's genotype are fully
      observed and matched but their haplotypes are missing. In this paper we describe
      how to deal with missing covariates of each individual for competing risks data.
      We suggest a procedure for estimating the cumulative incidence functions for a
      flexible class of regression models when there are missing data, and establish
      the large sample properties. Small sample properties are investigated using
      simulations in a setting that mimics the motivating haplotype matching problem.
      The proposed approach is then applied to the HCT study.

PMID- 22968449
TI  - Facile determination of formal transfer potentials for hydrophilic alkali metal
      ions at water|ionic liquid microinterfaces.
AB  - The formal transfer potentials of hydrophilic alkali metal ions Li(+), Na(+),
      K(+), Rb(+), and Cs(+) were determined at water|room temperature ionic liquid
      (w|RTIL) interfaces. A working curve for an interface held at the tip of a
      micropipette (25 MUm in diameter) was developed through simulated cyclic
      voltammograms (CVs) via finite element analysis with Comsol Multiphysics
      software. This methodology takes advantage of the symmetric diffusion regime
      experienced at the w|RTIL micropipette interface between two immiscible
      electrolytic solutions (micro-ITIES) which generates peak-shaped waves in the
      forward and reverse scans similar to those in CVs obtained at large (centimeter
      scale) ITIES. Through the simulation a profile of IT was generated in order to
      construct the working curve from which, in conjunction with experimentally
      obtained CVs, the formal transfer potentials were extrapolated. The unique
      characteristics of diffusion at an interface utilizing a pulled capillary make
      this approach possible. Additionally, within the simulation the geometry can be
      tailored to approximate closely the actual physical and experimental conditions.
      In this way the formal transfer potentials of Li(+), Na(+), K(+), Rb(+), and
      Cs(+) were found to be 0.565, 0.548, 0.521, 0.531, and 518 V, respectively, at
      the interface between water and our extremely hydrophobic ionic liquid,
      trihexyltetradecylphosphonium tetrakis(pentafluorophenyl)borate. The implications
      of these constants towards the evaluation of metal ion extractions will also be
      discussed.

PMID- 22968451
TI  - Antibodies to the C-terminus of laminin gamma1 are present in a distinct subgroup
      of patients with systemic and cutaneous lupus erythematosus.

PMID- 22968450
TI  - Recent trends of cancer mortality in Romanian adults: mortality is still
      increasing, although young adults do better than the middle-aged and elderly
      population.
AB  - We analysed the mortality trends (1986-2009) for all cancers combined and
      selected cancers in adult Romanians by three age groups (15-49, 50-69 and older
      than 70 years of age) in comparison with 11 other European countries. We
      extracted mortality data from the WHO database and grouped the countries into
      four regions: central and eastern Europe (Romania, Bulgaria, the Czech Republic,
      Hungary), Baltic countries (Estonia, Latvia and Lithuania), western and northern
      Europe (Austria, the Netherlands and Finland), and southern Europe (Croatia and
      Slovenia). Mortality rates were age-standardized against the standard European
      population. Significant changes in mortality trends were identified by Joinpoint
      regression and annual percentage changes (APCs) were calculated for periods with
      uniform trends. Cancer mortality in Romania was among the lowest in Europe in
      1986, but was higher than most countries by 2009. Despite the declining mortality
      (APC) in younger Romanians for all cancers combined (men-1.5% from 1997, women
      1.2% 1997-2004 and -3.8% 2004-2009), male lung cancer (-2.8% from 1997), female
      breast (-3.5% from 1999) and cervical (-5.4% from 2004) cancers, mortality has
      increased in middle-aged and elderly patients for most cancers analysed. The
      exception was declining stomach cancer mortality in most Romanians, except
      elderly men. For most cancers analysed, mortality declined in the Baltic
      countries in young and middle-aged patients, and in western and northern
      countries for all ages. Lung cancer mortality in women increased in all countries
      except Latvia. We urge immediate steps to reverse the alarming increase in cancer
      mortality among middle-aged and elderly Romanians.

PMID- 22968452
TI  - Opposite chirality of alpha-carotene in unusual cyanobacteria with unique
      chlorophylls, Acaryochloris and Prochlorococcus.
AB  - Among all photosynthetic and non-photosynthetic prokaryotes, only cyanobacterial
      species belonging to the genera Acaryochloris and Prochlorococcus have been
      reported to synthesize alpha-carotene. We reviewed the carotenoids, including
      their chirality, in unusual cyanobacteria containing diverse Chls. Predominantly
      Chl d-containing Acaryochloris (two strains) and divinyl-Chl a and divinyl-Chl b
      containing Prochlorococcus (three strains) contained beta-carotene and zeaxanthin
      as well as alpha-carotene, whereas Chl b-containing Prochlorothrix (one strain)
      and Prochloron (three isolates) contained only beta-carotene and zeaxanthin but
      no alpha-carotene as in other cyanobacteria. Thus, the capability to synthesize
      alpha-carotene seemed to have been acquired only by Acaryochloris and
      Prochlorococcus. In addition, we unexpectedly found that alpha-carotene in both
      cyanobacteria had the opposite chirality at C-6': (6'S)-chirality in
      Acaryochloris and normal (6'R)-chirality in Prochlorococcus, as reported in some
      green algae and land plants. The results represent the first evidence for the
      natural occurrence and biosynthesis of (6'S)-alpha-carotene. All the zeaxanthins
      in these species were of the usual (3R,3'R)-chirality. Therefore, based on the
      identification of the carotenoids and genome sequence data, we propose a
      biosynthetic pathway for the carotenoids, particularly alpha-carotene, including
      the participating genes and enzymes.

PMID- 22968453
TI  - Gene therapy for adenosine deaminase-deficient severe combined immune deficiency:
      clinical comparison of retroviral vectors and treatment plans.
AB  - We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)
      deficient severe combined immunodeficiency using 2 slightly different retroviral
      vectors for the transduction of patients' bone marrow CD34(+) cells. Four
      subjects were treated without pretransplantation cytoreduction and remained on
      ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient
      (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older
      subjects (15 and 20 years of age), whereas some gene marking of PBMC has
      persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six
      additional subjects were treated using the same gene transfer protocol, but after
      withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three
      of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene
      marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the
      normal range. Two subjects were restarted on ERT because of poor gene marking and
      immune recovery, and one had a subsequent allogeneic hematopoietic stem cell
      transplantation. These studies directly demonstrate the importance of providing
      nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits
      with gene therapy for ADA-deficient severe combined immunodeficiency.

PMID- 22968454
TI  - Role of the microenvironment in mantle cell lymphoma: IL-6 is an important
      survival factor for the tumor cells.
AB  - Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma
      frequently involved in the lymph nodes, bone marrow, spleen, and gastrointestinal
      tract. We examined the role of IL-6 in MCL. Human MCL cells expressed the
      membrane gp130 and soluble gp80, and some of them also secreted IL-6.
      Neutralizing autocrine IL-6 and/or blocking IL-6 receptors in IL-6(+)/gp80(+) MCL
      cells inhibited cell growth, enhanced the rate of spontaneous apoptosis, and
      increased sensitivity to chemotherapy drugs. For IL-6(-) or gp80(low) MCL cells,
      paracrine or exogenous IL-6 or gp80 protected the cells from stress-induced
      death. Knockdown of gp80 in gp80(high) MCL cells rendered the cells more
      sensitive to chemotherapy drugs, even in the presence of exogenous IL-6. In
      contrast, overexpression of gp80 in gp80(low)/IL-6(+) MCL cells protected the
      cells from chemotherapy drug-induced apoptosis in vitro and compromised the
      therapeutic effect of chemotherapy in vivo. IL-6 activated the Jak2/STAT3 and
      PI3K/Akt pathways in MCL, and the inhibition of these pathways completely or
      partially abrogated IL-6-mediated protection of MCL cells. Hence, our study
      identifies IL-6 as a key cytokine for MCL growth and survival and suggests that
      targeting the IL-6 pathway may be a novel way to improve the efficacy of
      chemotherapy in MCL patients.

PMID- 22968455
TI  - CD8 T cells express randomly selected KIRs with distinct specificities compared
      with NK cells.
AB  - Epistatic interactions between killer cell immunoglobulin-like receptors (KIRs)
      and their cognate HLA class I ligands have important implications for
      reproductive success, antiviral immunity, susceptibility to autoimmune conditions
      and cancer, as well as for graft-versus-leukemia reactions in settings of
      allogeneic stem cell transplantation. Although CD8 T cells are known to acquire
      KIRs when maturing from naive to terminally differentiated cells, little
      information is available about the constitution of KIR repertoires on human CD8 T
      cells. Here, we have performed a high-resolution analysis of KIR expression on
      CD8 T cells. The results show that most CD8 T cells possess a restricted KIR
      expression pattern, often dominated by a single activating or inhibitory KIR.
      Furthermore, the expression of KIR, and its modulation of CD8 T-cell function,
      was independent of expression of self-HLA class I ligands. Finally, despite
      similarities in the stochastic regulation of KIRs by the bidirectional proximal
      promoter, the specificity of inhibitory KIRs on CD8 T cells was often distinct
      from that of natural killer cells in the same individual. The results provide new
      insight into the formation of KIR repertoires on human T cells.

PMID- 22968456
TI  - A tissue-specific chromatin loop activates the erythroid ankyrin-1 promoter.
AB  - The human ankyrin-1 gene (ANK1) contains 3 tissue-specific alternative promoters.
      We have shown previously that the erythroid-specific ankyrin 1 (ANK1E) core
      promoter contains a 5' DNase I hypersensitive site (HS) with barrier insulator
      function that prevents gene silencing in vitro and in vivo. Mutations in the
      ANK1E barrier region lead to decreased ANK1 mRNA levels and hereditary
      spherocytosis. In this report, we demonstrate a second ANK1E regulatory element
      located in an adjacent pair of DNase I HS located 5.6 kb 3' of the ANK1E promoter
      at the 3' boundary of an erythroid-specific DNase I-sensitive chromatin domain.
      The 3' regulatory element exhibits enhancer activity in vitro and in transgenic
      mice, and it has the histone modifications associated with an enhancer element.
      One of the ANK1E 3'HS contains an NF-E2 binding site that is required for
      enhancer function. We show that a chromatin loop brings the 3' enhancer and NF-E2
      into proximity with the 5' barrier region including the ANK1E core promoter.
      These observations demonstrate a model for the tissue-specific activation of
      alternative promoters that may be applicable to the ~ 30% of mammalian genes with
      alternative promoters that exhibit distinct expression patterns.

PMID- 22968457
TI  - A novel conditioning regimen improves outcomes in beta-thalassemia major patients
      using unrelated donor peripheral blood stem cell transplantation.
AB  - We used a novel NF-08-TM transplant protocol based on intravenous busulfan,
      cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with beta
      thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell
      transplantation (PBSCT) from unrelated donors (UDs) with well-matched human
      leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT)
      from matched sibling donors (MSDs). The median age at transplantation was 6.0
      years (range, 0.6-15.0 years), and the ratio of male-to-female patients was
      56:26. The median follow-up time was 24 months (range, 12-39 months). The
      estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in
      the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative
      incidences of graft rejection and grades III-IV acute graft-versus-host disease
      were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%,
      respectively, in the MSD-HSCT group. The cumulative incidence of transplant
      related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group.
      In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar
      results to MSD-HSCTs and can be used to treat beta-thalassemia patients in the
      absence of MSDs.

PMID- 22968458
TI  - Inhibition of polyphosphate as a novel strategy for preventing thrombosis and
      inflammation.
AB  - Inorganic polyphosphates are linear polymers of orthophosphate that modulate
      blood clotting and inflammation. Polyphosphate accumulates in infectious
      microorganisms and is secreted by activated platelets; long-chain polyphosphate
      in particular is an extremely potent initiator of the contact pathway, a limb of
      the clotting cascade important for thrombosis but dispensable for hemostasis.
      Polyphosphate inhibitors therefore might act as novel antithrombotic/anti
      inflammatory agents with reduced bleeding side effects. Antipolyphosphate
      antibodies are unlikely because of polyphosphate's ubiquity and simple structure;
      and although phosphatases such as alkaline phosphatase can digest polyphosphate,
      they take time and may degrade other biologically active molecules. We now
      identify a panel of polyphosphate inhibitors, including cationic proteins,
      polymers, and small molecules, and report their effectiveness in vitro and in
      vivo. We also compare their effectiveness against the procoagulant activity of
      RNA. Polyphosphate inhibitors were antithrombotic in mouse models of venous and
      arterial thrombosis and blocked the inflammatory effect of polyphosphate injected
      intradermally in mice. This study provides proof of principle for polyphosphate
      inhibitors as antithrombotic/anti-inflammatory agents in vitro and in vivo, with
      a novel mode of action compared with conventional anticoagulants.

PMID- 22968459
TI  - IL-36 signaling amplifies Th1 responses by enhancing proliferation and Th1
      polarization of naive CD4+ T cells.
AB  - The interleukin-1 (IL-1) superfamily of cytokines comprises a set of pivotal
      mediators of inflammation. Among them, the action of IL-36 cytokines in immune
      responses has remained elusive. In a recent study, we demonstrated a direct
      effect of IL-36 on immune cells. Here we show that, among T cells, the IL-36
      receptor is predominantly expressed on naive CD4(+) T cells and that IL-36
      cytokines act directly on naive T cells by enhancing both cell proliferation and
      IL-2 secretion. IL-36beta acts in synergy with IL-12 to promote Th1 polarization
      and IL-36 signaling is also involved in mediating Th1 immune responses to
      Bacillus Calmette-Guerin infection in vivo. Our findings point toward a critical
      function of IL-36 in the priming of Th1 cell responses in vitro, and in adaptive
      immunity in a model of mycobacterial infection in vivo.

PMID- 22968460
TI  - Prothrombin activation in blood coagulation: the erythrocyte contribution to
      thrombin generation.
AB  - Prothrombin activation can proceed through the intermediates meizothrombin or
      prethrombin-2. To assess the contributions that these 2 intermediates make to
      prothrombin activation in tissue factor (Tf)-activated blood, immunoassays were
      developed that measure the meizothrombin antithrombin (mTAT) and alpha-thrombin
      antithrombin (alphaTAT) complexes. We determined that Tf-activated blood produced
      both alphaTAT and mTAT. The presence of mTAT suggested that nonplatelet surfaces
      were contributing to approximately 35% of prothrombin activation. Corn trypsin
      inhibitor-treated blood was fractionated to yield red blood cells (RBCs),
      platelet-rich plasma (PRP), platelet-poor plasma (PPP), and buffy coat. Compared
      with blood, PRP reconstituted with PPP to a physiologic platelet concentration
      showed a 2-fold prolongation in the initiation phase and a marked decrease in the
      rate and extent of alphaTAT formation. Only the addition of RBCs to PRP was
      capable of normalizing alphaTAT generation. FACS on glycophorin A-positive cells
      showed that approximately 0.6% of the RBC population expresses phosphatidylserine
      and binds prothrombinase (FITC Xa.factor Va). These data indicate that RBCs
      participate in thrombin generation in Tf-activated blood, producing a membrane
      that supports prothrombin activation through the meizothrombin pathway.

PMID- 22968461
TI  - How I treat HHV8/KSHV-related diseases in posttransplant patients.
AB  - Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV)
      primary infection and/or reactivations are associated with uncommon and sometimes
      fatal, neoplastic, and non-neoplastic diseases. HHV8-related clinical
      manifestations notably range from Kaposi sarcoma (KS) to either primary effusion
      lymphoma or multicentric Castleman disease B-cell malignancies, and from
      polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow
      failure and peripheral cytopenias, associated or not with hemophagocytic
      syndromes, and to acute hepatitis syndromes. We reviewed the patient series
      reported in the literature and summarized clinical management aspects, in terms
      of diagnosis, follow-up, and treatment. We described typical clinical
      presentations and histopathologic diagnostic features of these diseases, and we
      discussed the role of HHV8-specific serologic, molecular, and immunologic assays,
      particularly focusing on recent data from HHV8-specific T-cell monitoring in
      posttransplantation KS patients. We finally discussed actual therapeutic options,
      namely, the reduction or discontinuation of immunosuppressive therapy or the
      switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to
      antineoplastic chemotherapy, along with the use of antiherpesvirus agents as
      prophylactic or therapeutic measures, and treatment with rituximab in posttrans
      plantation multicentric Castleman disease patients and non-neoplastic HHV8
      associated syndromes.

PMID- 22968462
TI  - Regulating type 1 IFN effects in CD8 T cells during viral infections: changing
      STAT4 and STAT1 expression for function.
AB  - Type 1 IFNs can conditionally activate all of the signal transducers and
      activators of transcription molecules (STATs), including STAT4. The best
      characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of
      cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally
      stimulate STAT1- and STAT4-dependent effects in CD8 T cells, but that CD8 T cells
      responding to infections of mice with lymphocytic choriomenigitis virus have
      elevated STAT4 and lower STAT1 expression with significant consequences for
      modifying the effects of type 1 IFN exposure. The phenotype was associated with
      preferential type 1 IFN activation of STAT4 compared with STAT1. Stimulation
      through the TCR induced elevated STAT4 expression, and STAT4 was required for
      peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance
      to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is
      discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells,
      with STAT4 acting as a key molecule in driving optimal antigen-specific responses
      and overcoming STAT1-dependent inhibition of proliferation.

PMID- 22968464
TI  - SRSF2 mutations in primary myelofibrosis: significant clustering with IDH
      mutations and independent association with inferior overall and leukemia-free
      survival.
AB  - Among spliceosome component mutations, those involving SF3B1 are most frequent in
      myelodysplastic syndromes with ring sideroblasts (MDS-RS; ~ 75% incidence) and
      SRSF2 in chronic myelomonocytic leukemia (~ 28% incidence). We recently reported
      on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and
      primary myelofibrosis (PMF). In the current study, we examined the prevalence and
      prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32
      (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant
      associations were demonstrated between SRSF2 mutations and advanced age (P <
      .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03).
      SRSF2 mutations were associated with shortened overall (P < .01) and leukemia
      free (P < .01) survival; the adverse effect on survival was independent of DIPSS
      plus (P = .01; HR = 1.9; 95% CI, 1.1-3.0) and IDH mutations (P < .01; HR = 2.3;
      95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF,
      cluster with IDH mutations, and are independently predictive of poor outcome.

PMID- 22968463
TI  - Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for
      survival.
AB  - We have analyzed the role of the REL family members in Hodgkin lymphoma (HL).
      shRNA targeting of each REL member showed that HL was uniquely dependent on relB,
      in contrast to several other B-cell lymphomas. In addition, relA and c-rel shRNA
      expression also decreased HL cell viability. In exploring relB activation
      further, we found stable NF-kappaB inducing kinase (NIK) protein in several HL
      cell lines and that NIK shRNA also affected HL cell line viability. More
      importantly, 49 of 50 HL patient biopsies showed stable NIK protein, indicating
      that NIK and the noncanonical pathway are very prevalent in HL. Lastly, we have
      used a NIK inhibitor that reduced HL but not other B-cell lymphoma cell
      viability. These data show that HL is uniquely dependent on relB and that the
      noncanonical pathway can be a therapeutic target for HL. Furthermore, these
      results show that multiple REL family members participate in the maintenance of a
      HL phenotype.

PMID- 22968465
TI  - Relationship between asian dust and ischemic stroke: a time-stratified case
      crossover study.
AB  - BACKGROUND AND PURPOSE: Particulate matter is increasingly recognized as a cause
      of human diseases, including cardiovascular diseases. However, the association
      between Asian dust (AD), a windblown sand dust originating from mineral soil in
      the deserts of China and Mongolia, and the incidence of cardiovascular diseases
      is unclear. The aim of the present study was to elucidate whether AD is
      associated with the incidence of ischemic stroke. METHODS: This study
      investigated the onset time of 7429 consecutive patients with ischemic stroke who
      were admitted to seven stroke centers in Fukuoka, Japan, between June 1999 and
      March 2010. Meteorologic variables and air pollutants, including AD and suspended
      particulate matters, were investigated during the identical period. A time
      stratified case-crossover study was conducted to assess the association between
      AD and stroke incidence using a conditional logistic regression analysis.
      RESULTS: Although AD was not significantly associated with the overall incidence
      of ischemic stroke, there was a relationship specific to the stroke subtypes. AD
      was significantly associated with the incidence of atherothrombotic brain
      infarction after adjusting for expected confounders, including meteorologic
      variables and other air pollutants. No association was detected in other types of
      ischemic stroke. CONCLUSION: These data suggest that AD does not increase the
      overall incidence of ischemic stroke, but it is specifically associated with the
      risk of atherothrombotic brain infarction.

PMID- 22968466
TI  - Smartphone teleradiology application is successfully incorporated into a
      telestroke network environment.
AB  - BACKGROUND AND PURPOSE: ResolutionMD mobile application runs on a Smartphone and
      affords vascular neurologists access to radiological images of patients with
      stroke from remote sites in the context of a telemedicine evaluation. Although
      reliability studies using this technology have been conducted in a controlled
      environment, this study is the first to incorporate it into a real-world hub and
      spoke telestroke network. The study objective was to assess the level of
      agreement of brain CT scan interpretation in a telestroke network between hub
      vascular neurologists using ResolutionMD, spoke radiologists using a Picture
      Archiving and Communications System, and independent adjudicators. METHODS: Fifty
      three patients with stroke at the spoke hospital consented to receive a
      telemedicine consultation and participate in a registry. Each CT was evaluated by
      a hub vascular neurologist, a spoke radiologist, and by blinded telestroke
      adjudicators, and agreement over clinically important radiological features was
      calculated. RESULTS: Agreement (kappa and 95% CI) between hub vascular
      neurologists using ResolutionMD and (1) the spoke radiologist; and (2)
      independent adjudicators, respectively, were: identification of intracranial
      hemorrhage 1.0 (0.92-1.0), 1.0 (0.93-1.0), neoplasm 1.0 (0.92-1.0), 1.0 (0.93
      1.0), any radiological contraindication to thrombolysis 1.0 (0.92-1.0), 0.85
      (0.65-1.0), early ischemic changes 0.62 (0.28-0.96), 0.58 (0.30-0.86), and
      hyperdense artery sign 0.40 (0.01-0.80), 0.44 (0.06-0.81). CONCLUSIONS: CT head
      interpretations of telestroke network patients by vascular neurologists using
      ResolutionMD on Smartphones were in excellent agreement with interpretations by
      spoke radiologists using a Picture Archiving and Communications System and those
      of independent telestroke adjudicators using a desktop viewer. CLINICAL TRIAL
      REGISTRATION INFORMATION: www.clinicaltrials.gov unique identifier NCT00829361.

PMID- 22968467
TI  - National trends in utilization and outcomes of endovascular treatment of acute
      ischemic stroke patients in the mechanical thrombectomy era.
AB  - BACKGROUND AND PURPOSE: Because several new devices for mechanical thrombectomy
      have become available, the outcomes of patients undergoing endovascular treatment
      for acute ischemic stroke are expected to improve in the United States. We
      performed this analysis to evaluate trends in utilization of endovascular
      treatment and associated rates of death and disability among acute ischemic
      stroke patients over a 6-year period, including further assessment within age
      strata. METHODS: We obtained data for patients admitted to hospitals in the
      United States from 2004 to 2009 with a primary diagnosis of ischemic stroke using
      a large national database. We determined the rate and pattern of utilization, and
      associated in-hospital outcomes of endovascular treatment among ischemic stroke
      patients and further analyzed trends within age strata. Outcomes were classified
      as minimal disability, moderate to severe disability, and death based on
      discharge disposition and compared between 2 time periods: 2004 to 2007 (post
      MERCI) and 2008 to 2009 (post-Penumbra) approvals RESULTS: Of the 3,292,842
      patients admitted with ischemic stroke, 72,342 (2.2%) received intravenous
      thrombolytic treatment and 13 799 (0.4%) underwent endovascular treatment. There
      was a 6-fold increase in patients who underwent endovascular treatment (0.1% of
      ischemic strokes in 2004 vs 0.6% in 2009; P<0.001), with the patients aged>=85
      years having the lowest rate of utilization (0.2%). The rates of intracranial
      hemorrhage remained unchanged throughout the 6 years. In multivariate logistic
      regression analysis, after adjusting for age, gender, presence of hypertension,
      congestive heart failure, renal failure, and secondary intracranial hemorrhages,
      there was no difference in the rate of minimal disability between the 2 study
      intervals (2004-2007 vs 2008-2009; odds ratio, 0.8; 95% confidence interval, 0.7
      1.04; P=0.11). Mortality decreased while moderate to severe disability increased
      for patients treated during 2008 to 2009 (odds ratio, 0.7; 95% confidence
      interval, 0.6-0.9; P=0.007; and odds ratio, 1.4; 95% confidence interval, 1.2
      1.7; P=0.0002). CONCLUSIONS: There has been a significant increase in the
      proportion of acute ischemic stroke patients receiving endovascular treatment
      over the 6 years and reduction in in-hospital mortality. Our results highlight
      the need to implement endovascular techniques in a balanced manner across various
      age groups that also results in the reduction of disability in addition to
      mortality.

PMID- 22968468
TI  - Cranial irradiation increases risk of stroke in pediatric brain tumor survivors.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to determine the
      incidence of neurovascular events as late complications in pediatric patients
      with brain tumor and to evaluate radiation as a risk factor. METHODS: Patients
      were ascertained using the tumor database of a pediatric tertiary care center.
      Included patients had a primary brain tumor, age birth to 21 years, initial
      treatment January 1, 1993, to December 31, 2002, and at least 2 visits with neuro
      oncology. Radiation exposure included: whole brain, whole brain plus a focal
      boost, or focal brain. The primary outcome was stroke or transient ischemic
      attack. RESULTS: Of 431 subjects, 14 had 19 events of stroke or transient
      ischemic attack over a median follow-up of 6.3 years. The incidence rate was
      548/100 000 person-years. Overall, 61.5% of subjects received radiation,
      including 13 of 14 subjects with events. Median time from first radiation to
      first event was 4.9 years. The stroke/transient ischemic attack hazard ratio for
      any brain irradiation was 8.0 (95% CI, 1.05-62; P=0.045); for the circle of
      Willis, radiation was 9.0 (95% CI, 1.2-70; P=0.035); and for focal noncircle of
      Willis, radiation was 3.4 (95% CI, 0.21-55; P=0.38). CONCLUSIONS: The incidence
      of neurovascular events in this population is 100-fold higher than in the general
      pediatric population and cranial irradiation is an important risk factor. By
      defining the incidence of this late effect, physicians are better able to counsel
      parents regarding treatment, monitor patients at risk, and target a population
      for primary stroke prevention in future studies.

PMID- 22968469
TI  - Tick control practices in Burkina Faso and acaricide resistance survey in
      Rhipicephalus (Boophilus) geigyi (Acari: Ixodidae).
AB  - Traditional systems account for 95 % of the livestock produced in Burkina Faso.
      Tick infestation hampers livestock productivity in this area. However, little
      information exists on tick-control practices used by livestock farmers. We
      interviewed 60 stockbreeders working in traditional farming systems to obtain the
      first data on tick-control practices. Sixteen farmers (27 %) did not use
      conventional practices: seven removed ticks by hand or plastered cattle with dung
      or engine oil; nine farmers treated cattle with crop pesticides. Forty-four
      farmers (73 %) used mainly synthetic pyrethroids (SP; either alphacypermethrin or
      deltamethrin in 20 and 18 farms, respectively) and occasionally amitraz (N = 6).
      Intervals between treatments varied significantly depending on the chemical used:
      most farmers using crop pesticides (100 %), amitraz (100 %) or alphacypermethrin
      (80 %) adjusted tick-control to tick-burden, whereas farmers using deltamethrin
      tended more to follow a tick-control schedule. Perception of tick-control
      effectiveness significantly varied among practices: tick-control failures were
      more frequently reported by farmers using alphacypermethrin (55 %) than by those
      using either other conventional acaricides (17 %) or crop pesticides (0 %). We
      investigated whether this could indicate actual development of SP-resistance in
      cattle ticks. First, using the larval packet test technique, we confirmed that
      the computation of LC50 and LC90 was repeatable and remained stable across
      generations of the Rhipicephalus (Boophilus) geigyi Hounde laboratory strain. We
      then collected from the field fully-engorged female R. geigyi to evaluate the SP
      resistance relative to the Hounde reference strain. We did not detect any case of
      SP-resistance in the field-derived R. geigyi ticks.

PMID- 22968470
TI  - Effects of transjugular intrahepatic portosystemic shunt on changes in the small
      bowel mucosa of cirrhotic patients with portal hypertension.
AB  - BACKGROUND: The introduction of capsule endoscopy (CE) has facilitated the
      detection of mucosal changes in the small bowel, and such mucosal changes have
      been noted in cirrhotic patients with portal hypertension; these changes are
      described as portal hypertensive enteropathy. The aim of this study was to assess
      the effects of transjugular intrahepatic portosystemic shunt (TIPS) on the small
      bowel mucosal changes detected by CE in cirrhotic patients with portal
      hypertension. METHODS: TIPS was performed in fifteen cirrhotic patients with
      portal hypertension. All patients underwent CE before and 2 weeks after TIPS. The
      small bowel mucosal changes were defined as edema, angiodysplasia-like lesions,
      red spots, and small bowel varices. Changes in the portosystemic pressure
      gradient (PSG) and CE findings were evaluated. RESULTS: Before TIPS, small bowel
      edema was detected in all 15 patients, angiodysplasia-like lesions in 7, and red
      spots in 14 patients. The PSG decreased significantly, from 21.2 +/- 2.6 before
      TIPS to 8.9 +/- 3.3 mmHg (p < 0.001) after the procedure. After TIPS, the small
      bowel edema was attenuated in 8 of the 15 patients. In two patients with
      angiodysplasia-like lesions and 4 with red spots, these lesions were attenuated
      after TIPS. The average score for small bowel edema and the grade of red spots
      were reduced significantly after TIPS (2.3 +/- 0.7-1.8 +/- 0.6, p < 0.005 and 1.6
      +/- 0.9-1.3 +/- 0.7, p < 0.05, respectively). Small bowel varices were seen in 4
      patients before TIPS and all these varices disappeared after TIPS. CONCLUSIONS:
      In cirrhotic patients with portal hypertension, small bowel edema, red spots, and
      small bowel varices were attenuated after TIPS. Portal hypertension may be an
      important factor in the development of small bowel mucosal changes.

PMID- 22968472
TI  - Semi-autonomous liquid handling via on-chip pneumatic digital logic.
AB  - This report presents a liquid-handling chip capable of executing metering,
      mixing, incubation, and wash procedures largely under the control of on-board
      pneumatic circuitry. The only required inputs are four static selection lines to
      choose between the four machine states, and one additional line for power. State
      selection is simple: constant application of vacuum to an input causes the device
      to execute one of its four liquid handling operations. Programmed control of 31
      valves, including fast coordinated cycling for peristaltic pumping, is
      accomplished by pneumatic digital logic circuits built out of microfluidic valves
      and channels rather than electronics, eliminating the need for the off-chip
      control machinery that is typically required for integrated microfluidics.

PMID- 22968471
TI  - Polymorphisms in XPC provide prognostic information in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the most common type of adult leukemia for which
      cytosine arabinoside-based chemotherapy is the main treatment. Single nucleotide
      polymorphisms within the nucleotide excision repair pathway may alter the
      susceptibility of leukemia cells to chemotherapy. We investigated the roles of
      six single nucleotide polymorphisms (ERCC5rs76871136, ERCC5rs77569659,
      ERCC5rs873601, XPCrs2228000, XPCrs2228001, and XPCrs1870134) in the nucleotide
      excision repair pathway in influencing the outcome of patients with AML treated
      with cytosine arabinoside-based chemotherapy. One hundred fifty-one patients with
      AML in a Chinese population were enrolled in this study. Genotypes were
      determined by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. We found that the distribution of three genotypes of XPCrs1870134
      significantly differed in the cytogenetic risk groups (P = 0.04). A statistically
      significant correlation between polymorphisms of XPCrs2228001 and gender was
      found among the gender groups (P = 0.03). Moreover, patients carrying at least
      one variant allele (XPCrs2228001AA+CC) were more likely to respond better than
      those who did not carry a variant. However, no significant association was
      detected between polymorphisms in ERCC5 and treatment response. These findings
      suggest that XPC polymorphisms are important markers for the outcome of patients
      with AML in the Chinese population.

PMID- 22968473
TI  - Complementary and alternative approaches to the treatment of tension-type
      headache.
AB  - While pharmacotherapy with nonsteroidal anti-inflammatories (NSAIDs) and
      tricyclic antidepressants comprises the traditional treatment of tension-type
      headaches (TTH), the use of other therapeutic approaches in combination with
      medications can increase the success of treatment. Patients with comorbid mood
      disorders and frequent headaches may particularly benefit from some
      nonpharmacologic approaches. This review focuses on complementary and alternative
      approaches to tension-type headache treatment, including psychological therapies,
      acupuncture, and physical treatments. The current evidence indicates that EMG
      biofeedback (BFB) is effective in the treatment of TTH, and cognitive behavioral
      therapy and relaxation training may also be beneficial. Physical therapy and
      acupuncture may be considered in patients with frequent TTH, but the scientific
      basis is limited.

PMID- 22968474
TI  - Synthesis of a new series of pyridine and fused pyridine derivatives.
AB  - The reaction of 4-methyl-2-phenyl-1,2-dihydro-6-oxo-5-pyridine- carbonitrile (1)
      with arylidene malononitrile afforded isoquinoline derivatives 2a,b. 6-Chloro-4
      methyl-2-phenyl-5-pyridinecarbonitile (3) obtained by chlorination of compound 1
      with phosphoryl chloride was converted into 6-amino-4-methyl-2-phenyl-5
      pyridinecarbonitrile (4) and 6-hydrazido-4-methyl-2-phenyl-5-pyridinecarbonitrile
      (5) in good yield, through reactions with ammonium acetate and hydrazine hydrate,
      respectively. Treatment of 4 with ethyl acetoacetate, acetic anhydride, formic
      acid, urea and thiourea gave the corresponding pyrido [2,3-d] pyrimidine
      derivatives 7-10a,b. A new series of 6-substituted-4-methyl-2-phenyl-5-pyridine
      carbonitriles 11-13 has been synthesized via reaction of 4 with phenyl
      isothiocyanate, benzenesulphonyl chloride and acetic anhydride. Treatment of 4
      with malononitrile gave 1,8-naphthyridine derivative 14. The reactivity of
      hydrazide 5 towards acetic acid, phenylisothiocyanate and methylacrylate to give
      pyrazolo-[3,4-b]-pyridine derivatives 15-17 was studied. Treatment of 5 with
      acetic anhydride, phthalic anhydride and carbon disulphide gave pyridine
      derivatives 18,19 and 1,2,4-triazolo-[3,4-a]-pyridine derivative 20.

PMID- 22968475
TI  - Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by
      ethanolic extract of Gracilaria tenuistipitata.
AB  - The water extract of Gracilaria tenuistipitata have been found to be protective
      against oxidative stress-induced cellular DNA damage, but the biological function
      of the ethanolic extracts of G. tenuistipitata (EEGT) is still unknown. In this
      study, the effect of EEGT on oral squamous cell cancer (OSCC) Ca9-22 cell line
      was examined in terms of the cell proliferation and oxidative stress responses.
      The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose
      response manner (p < 0.0001). The annexin V intensity and pan-caspase activity of
      EEGT-treated OSCC cells were significantly increased in a dose-response manner (p
      < 0.05 to 0.0001). EEGT significantly increased the reactive oxygen species (ROS)
      level (p < 0.0001) and decreased the glutathione (GSH) level (p < 0.01) in a dose
      response manner. The mitochondrial membrane potential (MMP) of EEGT-treated OSCC
      cells was significantly decreased in a dose-response manner (p < 0.005). In
      conclusion, we have demonstrated that EEGT induced the growth inhibition and
      apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion,
      caspase activation, and mitochondrial depolarization. Therefore, EEGT may have
      potent antitumor effect against oral cancer cells.

PMID- 22968476
TI  - Thiolate-assisted cation exchange reaction for the synthesis of near-infrared
      photoluminescent Hg(x)Cd(1-x)Te nanocrystals.
AB  - In this paper, we report the synthesis of dot- and branch-shaped Hg(x)Cd(1-x)Te
      nanocrystals (NCs) with good stability and a high quantum yield of about 30%
      through an elaborate cation exchange reaction at room temperature. The large red
      shifts in both absorption spectra and photoluminescence (PL) spectra confirmed
      the substitution of mercury ions for cadmium ions and the formation of Hg(x)Cd(1
      x)Te NCs. Interesting periodical XRD peaks observed in as-obtained Hg(x)Cd(1-x)Te
      NCs indicated the formation of layered metal thiolates, which not only played a
      key role in introducing mercury ions during the cation exchange process, but also
      acted as ligands to maintain the emission stability of newly formed Hg(x)Cd(1
      x)Te NCs. The results indicate that the red-shift in PL emission has close
      correlation with several parameters (such as the amounts of thiols and mercury
      ions, the sample store time, etc.).

PMID- 22968477
TI  - 'Been there done that': disentangling option value effects from user
      heterogeneity when valuing natural resources with a use component.
AB  - Endogeneity bias arises in contingent valuation studies when the error term in
      the willingness to pay (WTP) equation is correlated with explanatory variables
      because observable and unobservable characteristics of the respondents affect
      both their WTP and the value of those variables. We correct for the endogeneity
      of variables that capture previous experience with the resource valued, humpback
      whales, and with the geographic area of study. We consider several endogenous
      behavioral variables. Therefore, we apply a multivariate Probit approach to
      jointly model them with WTP. In this case, correcting for endogeneity increases
      econometric efficiency and substantially corrects the bias affecting the
      estimated coefficients of the experience variables, by isolating the decreasing
      effect on option value caused by having already experienced the resource. Stark
      differences are unveiled between the marginal effects on WTP of previous
      experience of the resource in an alternative location versus experience in the
      location studied, Newfoundland and Labrador (Canada).

PMID- 22968478
TI  - Displaying high-affinity ligands on adeno-associated viral vectors enables tumor
      cell-specific and safe gene transfer.
AB  - Gene transfer vectors derived from the adeno-associated virus (AAV) have recently
      received increasing attention due to substantial therapeutic benefit in several
      clinical trials. Nevertheless, their great potential for in vivo gene therapy can
      only be partially exploited owing to their broad tropism. Current cell surface
      targeting strategies expanded vector tropism towards transduction of cell types
      that are inefficiently infected naturally, but failed to restrict or fully re
      direct AAV's tropism. Hypothesizing that this limitation can be overcome by
      equipping natural receptor-blinded AAV vectors with high-affinity ligands, we
      displayed designed ankyrin repeat proteins (DARPin) as VP2 fusion proteins on AAV
      capsids ablated for natural primary receptor binding. These second generation
      targeting vectors demonstrated an as of yet unachieved efficiency to discriminate
      between target and non-target cells in mono- and mixed cultures. Moreover, DARPin
      AAV vectors delivered a suicide gene precisely to tumor tissue and substantially
      reduced tumor growth without causing fatal liver toxicity. The latter caused
      death in animals treated with conventional AAV vectors with unmodified capsids,
      which accumulated in liver tissue and failed to affect tumor growth. This novel
      targeting platform will be key to translational approaches requiring restricted
      and cell type-specific in vivo gene delivery.

PMID- 22968479
TI  - Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7
      exon skipping.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting
      from lesions of the gene encoding dystrophin. These usually consist of large
      genomic deletions, the extents of which are not correlated with the severity of
      the phenotype. Out-of-frame deletions give rise to dystrophin deficiency and
      severe DMD phenotypes, while internal deletions that produce in-frame mRNAs
      encoding truncated proteins can lead to a milder myopathy known as Becker
      muscular dystrophy (BMD). Widespread restoration of dystrophin expression via
      adeno-associated virus (AAV)-mediated exon skipping has been successfully
      demonstrated in the mdx mouse model and in cardiac muscle after percutaneous
      transendocardial delivery in the golden retriever muscular dystrophy dog (GRMD)
      model. Here, a set of optimized U7snRNAs carrying antisense sequences designed to
      rescue dystrophin were delivered into GRMD skeletal muscles by AAV1 gene transfer
      using intramuscular injection or forelimb perfusion. We show sustained correction
      of the dystrophic phenotype in extended muscle areas and partial recovery of
      muscle strength. Muscle architecture was improved and fibers displayed the
      hallmarks of mature and functional units. A 5-year follow-up ruled out immune
      rejection drawbacks but showed a progressive decline in the number of corrected
      muscle fibers, likely due to the persistence of a mild dystrophic process such as
      occurs in BMD phenotypes. Although AAV-mediated exon skipping was shown safe and
      efficient to rescue a truncated dystrophin, it appears that recurrent treatments
      would be required to maintain therapeutic benefit ahead of the progression of the
      disease.

PMID- 22968480
TI  - CD166(pos) subpopulation from differentiated human ES and iPS cells support
      repair of acute lung injury.
AB  - Previous efforts to derive lung progenitor cells from human embryonic stem (hES)
      cells using embryoid body formation or stromal feeder cocultures had been limited
      by low efficiencies. Here, we report a step-wise differentiation method to drive
      both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our
      data demonstrated a 30% efficiency in generating lung epithelial cells (LECs)
      that expresses various distal lung markers. Further enrichment of lung progenitor
      cells using a stem cell marker, CD166 before transplantation into bleomycin
      injured NOD/SCID mice resulted in enhanced survivability of mice and improved
      lung pulmonary functions. Immunohistochemistry of lung sections from surviving
      mice further confirmed the specific engraftment of transplanted cells in the
      damaged lung. These cells were shown to express surfactant protein C, a specific
      marker for distal lung progenitor in the alveoli. Our study has therefore
      demonstrated the proof-of-concept of using iPS cells for the repair of acute lung
      injury, demonstrating the potential usefulness of using patient's own iPS cells
      to prevent immune rejection which arise from allogenic transplantation.

PMID- 22968481
TI  - Exon 45 skipping through U1-snRNA antisense molecules recovers the Dys-nNOS
      pathway and muscle differentiation in human DMD myoblasts.
AB  - Exon skipping has been demonstrated to be a successful strategy for the gene
      therapy of Duchenne muscular dystrophy (DMD): the rational being to convert
      severe Duchenne forms into milder Becker ones. Here, we show the selection of U1
      snRNA-antisense constructs able to confer effective rescue of dystrophin
      synthesis in a Delta44 Duchenne genetic background, through skipping of exon 45;
      moreover, we demonstrate that the resulting dystrophin is able to recover timing
      of myogenic marker expression, to relocalize neuronal nitric oxide synthase
      (nNOS) and to rescue expression of miRNAs previously shown to be sensitive to the
      Dystrophin-nNOS-HDAC2 pathway. Becker mutations display different phenotypes,
      likely depending on whether the shorter protein is able to reconstitute the wide
      range of wild-type functions. Among them, efficient assembly of the dystrophin
      associated protein complex (DAPC) and nNOS localization are important. Comparing
      different Becker deletions we demonstrate the correlation between the ability of
      the mutant dystrophin to relocalize nNOS and the expression levels of two miRNAs,
      miR-1 and miR29c, known to be involved in muscle homeostasis and to be controlled
      by the Dys-nNOS-HDAC2 pathway.

PMID- 22968482
TI  - Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in
      cerebellum, striatum and hippocampus of juvenile rats.
AB  - The use of psychostimulant methylphenidate has increased in recent years for the
      treatment of attention-deficit hyperactivity disorder in children and
      adolescents. However, the behavioral and neurochemical changes promoted by its
      use are not yet fully understood, particularly when used for a prolonged period
      during stages of brain development. Thus, the aim of this study was to determine
      some parameters of oxidative stress in encephalic structures of juvenile rats
      subjected to chronic methylphenidate treatment. Wistar rats received
      intraperitoneal injections of methylphenidate (2.0 mg/kg) once a day, from the
      15th to the 45th day of age or an equivalent volume of 0.9% saline solution
      (controls). Two hours after the last injection, animals were euthanized and the
      encephalic structures obtained for determination of oxidative stress parameters.
      Results showed that methylphenidate administration increased the activities of
      superoxide dismutase and catalase, but did not alter the levels of reactive
      species, thiobarbituric acid reactive substances levels and sulfhydryl group in
      cerebellum of rats. In striatum and hippocampus, the methylphenidate-treated rats
      presented a decrease in the levels of reactive species and thiobarbituric acid
      reactive substances, but did not present changes in the sulfhydryl groups levels.
      In prefrontal cortex, methylphenidate promoted an increase in reactive species
      formation, SOD/CAT ratio, and increased the lipid peroxidation and protein
      damage. These findings suggest that the encephalic structures respond differently
      to methylphenidate treatment, at least, when administered chronically to young
      rats. Notably, the prefrontal cortex of juvenile rats showed greater sensitivity
      to oxidative effects promoted by methylphenidate in relation to other encephalic
      structures analyzed.

PMID- 22968484
TI  - Prevalence of thoracic vertebral fractures in hospitalized elderly patients with
      heart failure.
AB  - OBJECTIVE: Heart failure (HF) has been associated with increased risk of
      fragility fractures. Indeed, most literature data on fractures were based on an
      historical and clinical approach focused on the identification of peripheral
      fractures, whereas the risk of vertebral fractures in this clinical setting is
      still unclear. DESIGN: Cross-sectional study. AIM: To evaluate the prevalence and
      determinants of radiological thoracic vertebral fractures in patients with HF.
      METHODS: The study includes 1031 elderly hospitalized patients (491 females and
      540 males; median age, 75 years; range, 65-90; 430 patients with HF) who were
      evaluated for the presence of thoracic vertebral fractures by quantitative
      morphometric analysis, using chest X-ray routinely performed in the diagnostic
      work-up of HF. RESULTS: Vertebral fractures were found in 166 patients (16.1%),
      the prevalence being significantly higher in patients with HF as compared with
      those without HF, both in females (30.9 vs 15.8%; P<0.001) and in males (16.4 vs
      7.4%; P=0.001). The association between HF and vertebral fractures remained
      statistically significant (odds ratio, 2.14; 95% CI, 1.25-3.66; P=0.01) even
      after adjustment for age, sex, loop diuretic therapy, anticoagulant therapy,
      proton pump therapy, coexistent chronic obstructive pulmonary disease, diabetes
      mellitus, renal insufficiency, and chronic liver diseases. In patients with HF,
      vertebral fractures were positively correlated with female sex, duration of HF,
      ischemic heart disease, cigarette smoking, and treatment with anti-osteoporotic
      drugs, and inversely correlated with left ventricular ejection fraction.
      CONCLUSIONS: Hospitalized patients suffering from HF are at higher risk of
      vertebral fractures than patients without HF in the same clinical context.

PMID- 22968483
TI  - Genotypes in relation to phenotypic appearance and exposure to environmental
      factors in Graves' hyperthyroidism.
AB  - BACKGROUND: Genetic polymorphisms and environmental factors are both involved in
      the pathogenesis of Graves' disease, but their interaction and effect on Graves'
      phenotypes have scarcely been investigated. OBJECTIVE: To test the hypothesis
      that subjects with susceptibility genotypes develop more severe Graves'
      hyperthyroidism at a younger age and after less exposure to environmental
      factors, with attention to gender differences. STUDY DESIGN: A prospective
      observational multicenter study in 205 adult Caucasian patients with untreated
      first episode of Graves' hyperthyroidism. METHODS: Evaluation of genotypes (HLA
      DRB1*03, DQA1*05, DQB1*02; CTLA4 49A/G, CT60 A/G; PTPN22 C/T) in relation to
      phenotypes (age, sex, severity (clinical, biochemical, and immunological)) of
      hyperthyroidism and environmental factors (smoking, stress questionnaires).
      RESULTS: G-alleles in CTLA4 single nucleotide polymorphisms were dose-dependently
      associated with younger age at the time of diagnosis and less exposure to daily
      hassles. In gender-specific analysis, this association is enhanced in men and
      attenuated in women. Males (but not females) in HLA linkage disequilibrium had
      more severe (biochemical and immunological) hyperthyroidism and a tendency to
      younger age at diagnosis, compared with those not in linkage disequilibrium.
      CONCLUSION: Graves' hyperthyroidism occurs at a younger age with less exposure to
      environmental factors in subjects carrying susceptibility genotypes. The impact
      of genotypes seems to be greater in males than in females.

PMID- 22968485
TI  - Muscle inflammatory signaling in response to 9 days of physical inactivity in
      young men with low compared with normal birth weight.
AB  - OBJECTIVE: The molecular mechanisms linking physical inactivity and muscle
      insulin resistance in humans have been suggested to include increased muscle
      inflammation, possibly associated with impaired oxidative metabolism. We employed
      a human bed rest study including 20 young males with normal birth weight (NBW)
      and 20 with low birth weight (LBW) and increased risk of diabetes. METHODOLOGY:
      The subjects were studied before and after 9 days of bed rest using the
      euglycemic-hyperinsulinemic clamp and muscle biopsy excision. Muscle inflammatory
      status was assessed as nuclear factor-kappaB (NF-kappaB) activity and mRNA
      expression of the pro-inflammatory MCP1 (CCL2) and IL6 and the macrophage marker
      CD68. Furthermore, mRNA expression of genes central to oxidative phosphorylation
      (OXPHOS) was measured including ATP5O, COX7A1, NDUFB6, and UQCRB. RESULTS: At
      baseline, muscle inflammatory status was similar in NBW and LBW individuals.
      After bed rest, CD68 expression was increased in LBW (P=0.03) but not in NBW
      individuals. Furthermore, expression levels of all OXPHOS genes were reduced
      after bed rest in LBW (P <= 0.05) but not in NBW subjects and were negatively
      correlated with CD68 expression in LBW subjects (P <= 0.03 for all correlations).
      MCP1 expression and NF-kappaB activity were unaffected by bed rest, and IL6
      expression was too low for accurate measurements. None of the inflammatory
      markers correlated with insulin sensitivity. CONCLUSIONS: Although LBW subjects
      exhibit disproportionately elevated CD68 mRNA expression suggesting macrophage
      infiltration and reduced OXPHOS gene expression when exposed to bed rest, our
      data altogether do not support the notion that bed rest-induced (9 days) insulin
      resistance is caused by increased muscle inflammation.

PMID- 22968486
TI  - Serum myostatin levels are negatively associated with abdominal aortic
      calcification in older men: the STRAMBO study.
AB  - OBJECTIVE: To assess the association between abdominal aortic calcification (AAC)
      and serum levels of myostatin, a negative regulator of skeletal muscle mass,
      which has been implicated in the development of atherosclerotic lesions in mice.
      DESIGN AND PATIENTS: We assessed AAC semiquantitatively from the lateral spine
      scans obtained using dual energy X-ray absorptiometry in 1071 men aged 20-87
      years. Serum myostatin levels were measured by an immunoassay that detects all
      myostatin forms. RESULTS: Total myostatin serum levels did not differ between men
      with or without self-reported ischemic heart disease, hypertension, or diabetes
      mellitus. Total serum myostatin levels were higher in men with higher serum
      calcium levels and lower in men with higher serum concentrations of highly
      sensitive C-reactive protein. Men with AAC had lower myostatin levels compared
      with men without AAC. Prevalence of AAC (AAC score > 0) was lower in the highest
      myostatin quartile compared with the three lower quartiles (P < 0.05). After
      adjustment for confounders, odds of AAC (AAC score > 0) were lower (OR=0.62; 95%
      confidence interval (95% CI), 0.45-0.85; P< 0.005) for the fourth myostatin
      quartile vs the three lower quartiles combined. In the sub-analysis of 745 men
      aged 60 years, the results were similar: AAC prevalence was lower in the highest
      myostatin quartile compared with the three lower quartiles combined (OR=0.54; 95%
      CI, 0.38-0.78; P<0.001). CONCLUSIONS: In older men, total myostatin serum levels
      are inversely correlated with AAC. Further studies are needed to investigate
      mechanisms underlying this association and to assess utility of myostatin as a
      cardiovascular marker.

PMID- 22968487
TI  - Delayed diagnosis of adrenal insufficiency in a patient with severe penoscrotal
      hypospadias due to two novel P450 side-change cleavage enzyme (CYP11A1) mutations
      (p.R360W; p.R405X).
AB  - CONTEXT: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first
      and rate-limiting step of steroidogenesis, the conversion of cholesterol to
      pregnenolone. CYP11A1 deficiency is commonly associated with adrenal
      insufficiency, and in 46,XY individuals, with variable degrees of disorder of sex
      development (DSD). PATIENT AND METHODS: The patient was born with
      hyperpigmentation, micropenis, penoscrotal hypospadias, and mild cryptorchidism.
      Biochemical and hormonal findings were normal except for low testosterone and low
      borderline cortisol. However, no short synacthen test was undertaken. Development
      was unremarkable apart from an episode labeled as sepsis with documented
      hyperkalemia and elevated C-reactive protein at age 15 days. Diagnosis of 46,XY
      DSD was made at age 2.5 months. Progression of hyperpigmentation prompted further
      investigations and the diagnosis of adrenal insufficiency was established at 2
      years with raised ACTH, normal renin activity, and failure of cortisol to respond
      to short synacthen test. Genetic analyses were performed. The novel CYP11A1
      mutations were characterized in vitro and in silico. RESULTS: The patient was
      compound heterozygous for two novel CYP11A1 mutations, p.R360W and p.R405X.
      p.R360W retained 30-40% of wild-type activity. In silico analyses confirmed these
      findings and indicated that p.R405X is severe. CONCLUSIONS: This study
      demonstrates the pathogenicity of two novel CYP11A1 mutations found in a patient
      with delayed diagnosis of CYP11A1 deficiency. Patients with partial deficiencies
      of steroidogenic enzymes are at risk to be misdiagnosed if adrenal function is
      not assessed. The adrenocortical function should be routinely assessed in all
      patients with DSD including severe hypospadias of unknown origin to prevent life
      threatening adrenal crises.

PMID- 22968488
TI  - The prevalence and risk factors of hepatitis B virus infection in an adult
      population in Romania:  a nationwide survey.
AB  - AIM: The prevalence and risk factors of hepatitis B virus (HBV) infection in the
      general population in Romania are still largely unknown. METHODS: A nationwide
      cross-sectional survey among a Romanian adult population (18-69 years) was
      conducted during 2006-2008 using a stratified, multistage sampling design. A
      total of 17 600 individuals were enrolled randomly into the study; the prevalence
      of chronic HBV infection (HBsAg-positive and anti-HBcAb-positive samples) was
      assessed on 13 127 individuals (74.6%) and a history of previous HBV infection
      (anti-HBcAb-positive, but HBsAg-negative samples) was assessed on 12 470
      individuals (70.5%). A questionnaire was used to collect information on the
      sociodemographic characteristics of the participants and the potential risk
      factors for HBV transmission. RESULTS: The overall prevalence rate of HBV chronic
      infection among all the participants tested was 4.4% (confidence interval: 4.0
      4.8%), with significant differences (P=0.0001) between participants from the main
      geographical regions of residence (Moldavia 4.5%, Muntenia and Dobrogea 5.4%, and
      Transylvania and Banat 3.1%). The total prevalence of previous HBV infection of
      all participants was 27.0% (confidence interval: 26.2-27.8%). The proportion of
      individuals with previous HBV infection, as well as with chronic HBV infection,
      showed a statistically significant increasing trend with age. The personal
      history of blood or blood product transfusion, surgical interventions, tattooing,
      and alcohol consumption greater than 60 g/day were risk factors associated with
      both anti-HBcAb and HBsAg seropositivity. CONCLUSION: A prevalence rate of 4.4
      and 27.0% for HBsAg and anti-HBcAb, respectively, represents a high figure within
      the European Union and a strong motivation for developing adequate strategies for
      prevention, active detection, and treatment of HBV infection in Romania.

PMID- 22968489
TI  - The nature of the different environmental sensitivity of symmetrical and
      unsymmetrical cyanine dyes: an experimental and theoretical study.
AB  - Symmetrical and unsymmetrical cyanine dyes are used in different applications due
      to their different fluorogenic behaviors toward bio-macromolecules and micro
      environments. In the present paper, computational studies on these dyes reveal
      that the potential energy of the electronic excited state is controlled by C-C
      bond rotational motion, which causes mainly nonradiative deactivation, according
      to the activation energies for the rotation. The rotations of different C-C bonds
      in the molecules have quite different rotational activation energies. Symmetrical
      dyes (Cy) possess an obviously higher rotating energy barrier as well as a larger
      energy gap compared to unsymmetrical dyes (TO). The C-C bond rotation close to
      the quinoline moiety of unsymmetrical thiazole orange (TO) allows the dye to
      possess the lowest energy barrier and also the lowest energy gap. This rotation
      plays a major role in reducing fluorescence quantum yields and providing a low
      fluorescent background in the free states of the unsymmetrical cyanine dyes. The
      results might provide a foundation for the interpretation of the behavior of the
      dyes and are useful for the future design of new cyanine fluorophores.

PMID- 22968490
TI  - In vivo two-photon fluorescent imaging of fluoride with a desilylation-based
      reactive probe.
AB  - A two-photon excitable molecular probe for fluoride, developed based on a
      fluoride-specific desilylation reaction, is demonstrated to be useful for
      fluorescent imaging of fluoride ions in live zebrafish by one-photon as well as
      two-photon microscopy for the first time.

PMID- 22968492
TI  - Sperm freezing in transsexual women.

PMID- 22968491
TI  - Examining the validity of cyclothymic disorder in a youth sample: replication and
      extension.
AB  - DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II,
      cyclothymic disorder and bipolar not otherwise specified (NOS). However,
      cyclothymic disorder in children is rarely researched, or often subsumed in an
      "NOS" category. The present study tests the replicability of findings from an
      earlier study, and expands on the criterion validity of cyclothymic disorder in
      youth. Using the Robins and Guze (1970) framework we examined the validity of
      cyclothymic disorder as a subtype of BP. Using a youth (ages 5-17) outpatient
      clinical sample (N = 894), participants with cyclothymic disorder (n = 53) were
      compared to participants with other BP spectrum disorders (n = 399) and to
      participants with non-bipolar disorders (n = 442). Analyses tested differences in
      youth with cyclothymic disorder and bipolar disorder not otherwise specified who
      do, and those who do not, have a parent with BP. Compared to youth with non
      bipolar disorders, youth with cyclothymic disorder had higher irritability (p <
      0.001), more comorbidity (p < 0.001), greater sleep disturbance (p < 0.005), and
      were more likely to have a family history of BP (p < 0.001). Cyclothymic disorder
      was associated with a younger age of onset compared to depression (p < 0.001) and
      bipolar II (p = 0.05). Parental BP status was not significantly associated with
      any variables. Results support that cyclothymic disorder belongs on the bipolar
      spectrum. Epidemiological studies indicate that cyclothymic disorder is not
      uncommon and involves significant impairment. Failing to differentiate between
      cyclothymic disorder and bipolar NOS limits our knowledge about a significant
      proportion of cases of bipolarity.

PMID- 22968493
TI  - Sample size policy for qualitative studies using in-depth interviews.

PMID- 22968494
TI  - Updates on treatment of attention-deficit/hyperactivity disorder: facts,
      comments, and ethical considerations.
AB  - OPINION STATEMENT: Within the last 2 years the bulk of information on evidence
      based treatments in ADHD was reviewed quite intensively and new empirical studies
      could be added. This update reports comprehensively about actual and essential
      facts in the field related to brain development and sensitive periods, predictors
      of treatment, safety of medication, value of naturalistic studies, new drugs and
      complementary medicine, behavioral interventions including neurofeedback and
      psychosocial treatment, treatment of comorbidity, and ethical considerations
      including preventive aspects. The updated combination of well selected evidence
      based treatments (ie, pharma plus non-pharma) seems to be clinically and
      ethically recommended as also suggested by the European and American guidelines
      on ADHD.

PMID- 22968495
TI  - A microfluidic platform for rapid, stress-induced antibiotic susceptibility
      testing of Staphylococcus aureus.
AB  - The emergence and spread of bacterial resistance to ever increasing classes of
      antibiotics intensifies the need for fast phenotype-based clinical tests for
      determining antibiotic susceptibility. Standard susceptibility testing relies on
      the passive observation of bacterial growth inhibition in the presence of
      antibiotics. In this paper, we present a novel microfluidic platform for
      antibiotic susceptibility testing based on stress-activation of biosynthetic
      pathways that are the primary targets of antibiotics. We chose Staphylococcus
      aureus (S. aureus) as a model system due to its clinical importance, and we
      selected bacterial cell wall biosynthesis as the primary target of both stress
      and antibiotic. Enzymatic and mechanical stresses were used to damage the
      bacterial cell wall, and a beta-lactam antibiotic interfered with the repair
      process, resulting in rapid cell death of strains that harbor no resistance
      mechanism. In contrast, resistant bacteria remained viable under the assay
      conditions. Bacteria, covalently-bound to the bottom of the microfluidic channel,
      were subjected to mechanical shear stress created by flowing culture media
      through the microfluidic channel and to enzymatic stress with sub-inhibitory
      concentrations of the bactericidal agent lysostaphin. Bacterial cell death was
      monitored via fluorescence using the Sytox Green dead cell stain, and rates of
      killing were measured for the bacterial samples in the presence and absence of
      oxacillin. Using model susceptible (Sanger 476) and resistant (MW2) S. aureus
      strains, a metric was established to separate susceptible and resistant
      staphylococci based on normalized fluorescence values after 60 min of exposure to
      stress and antibiotic. Because this ground-breaking approach is not based on
      standard methodology, it circumvents the need for minimum inhibitory
      concentration (MIC) measurements and long wait times. We demonstrate the
      successful development of a rapid microfluidic-based and stress-activated
      antibiotic susceptibility test by correctly designating the phenotypes of 16
      additional clinically relevant S. aureus strains in a blinded study. In addition
      to future clinical utility, this method has great potential for studying the
      effects of various stresses on bacteria and their antibiotic susceptibility.

PMID- 22968497
TI  - [The evolution of surgical and functional operability in thoracic oncology].
AB  - The authors own the experience of 4157 operations on the reason of malignant lung
      tumors, of them 429 (10.3%) operations were combined. The extracorporeal membrane
      oxygenation is considered to be reasonable by extended thoracic resections.
      Surgical lung volume reduction by emphysema shows good functional results, which
      allows to use its principles in oncologic patients with low functional repiratory
      reserves. The overall multidisciplinary approach in thoracic oncology allows
      better treatment results and gives hope to the earlier inoperable patients.

PMID- 22968496
TI  - Semi-mechanistic modeling of the interaction between the central and peripheral
      effects in the antinociceptive response to lumiracoxib in rats.
AB  - The model-based approach was undertaken to characterize the interaction between
      the peripheral and central antinociceptive effects exerted by lumiracoxib. The
      effects of intraplantar and intrathecal administrations and of fixed ratio
      combinations of lumiracoxib simultaneously administered by these two routes were
      evaluated using the formalin test in rats. Pain-related behavior data, quantified
      as the number of flinches of the injected paw, were analyzed using a population
      approach with NONMEM 7. The pain response during the first phase of the formalin
      test, which was insensitive to lumiracoxib, was modeled using a monoexponential
      decay. The second phase, which was sensitive to lumiracoxib, was described
      incorporating synthesis and degradation processes of pain mediators that were
      recruited locally after tissue injury. Upregulation at the local level and in the
      central nervous system (CNS) was set to be proportional to the predicted levels
      of pain mediators in the local (injured) compartment. Results suggest a greater
      role of upregulated COX-2(Local) in generating the pain response compared to COX
      2(CNS). Drug effects were described as inhibition of upregulated COX-2. The model
      adequately described the time course of nociception after formalin injection in
      the absence or presence of lumiracoxib administered locally and/or spinally. Data
      suggest that the overall response is the additive outcome of drug effects at the
      peripheral and central compartments, with predominance of peripheral mechanisms.
      Application of modeling opens new perspectives for understanding the overall
      mechanism of action of analgesic drugs.

PMID- 22968498
TI  - [The surgical treatment of hydatid disease of liver and lungs: the state of art].
AB  - Results of surgical treatment of 65 patients with the combined hydatid disease
      were analyzed. Lung invasion was combind with liver cysts in 57 patients, spleen 
      - in 2 patients, soft tissues of the thorax - in 2 patients and retroperitoneal
      cysts were found in 3 patients. Lung echinococcectomy with the use of
      minithoracotomy proved to be a method of choice. The access permits early
      recovery and shorter rehabilitation period, allowing to perform the second liver
      surgery on the 3--7th day after the first operation.

PMID- 22968499
TI  - [The surgical treatment of patients with lung cancer and severe cardiovascular
      disorders].
AB  - During the period of 1991--2010 yy 51 patients with lung cancrs were operated on
      the severe cardiovascular diseases (IHD -- 90%; critical carotid stenosis -- 6%;
      tricuspidal valve failure -- 2% and the combination of the IHD and aortic valve
      failure -- 2%). Lung cancer steged I in 17 (33.3%) patients, II in 15 (29.4%);
      III - in 16 (31.4%) and IV in 3 (5.9%) patients. 33 patients of 51 were radically
      operated on lung cancer, palliative resections were performed in 3; trial
      thoracotomies were performed in 2 patients. 8 (15.7%) patients were operated on
      simultaneously. The complicated postoperative period was registered in 22 (57.9%)
      patients of 38 with exitus lethalis in 2 cases. The complication rate after
      simultaneous operation was 62.5% with lethality of 12.5%, whereas by the
      consecutive operations the complication rate was 56.7% with lethality of 3.3%,
      Nevertheless, surgical correction of the severe concurrent cardiovascular
      pathology flares the range of operable patients with lung cancer.

PMID- 22968500
TI  - [The mechanoreceptor tactile diagnostics of thoracic diseases].
AB  - The novel system of tactile analysis was used in the mechanoreceptor device. The
      local pressure measurement is carried out in in cameras, divided by the elastic
      membrane from the analyzed organ. The devise allows fast and adequate real-time
      measurement of tissue density and elasticity. The results, acquired with the use
      of the mechanoreceptor device were checked microscopically. The study showed high
      compatibility and adequacy of the novel mechanoreceptor.

PMID- 22968501
TI  - [Treatment of bronchiectasis in children].
AB  - The thoracoscopic and traditional thoracotomic surgical access for bronchiectesis
      treatment in children were compared. The first (thoracoscopic) group included 18
      children. The control (thoracotomic) group included 26 patients. The mean
      operative time in the 1st group was 78.3+/-31 min; pleural draining lasted for
      1.3 days and postoperative hospital stay was 9.93+/-2.08 days. The mean operative
      time in the 2nd group was 81.7+/-35.1 min; pleural draining lasted for 3.3 days
      and postoperative hospital stay was 14.4+/-3.4 days. Conversion was needed in 4
      cases. Therefor, the thoracoscopic surgery proved to be much more preferable in
      children because of its' minimal invasiveness.

PMID- 22968502
TI  - [The surgical treatment of varicocele in children and adolescents in the
      outpatient setting].
AB  - The first group included 45 patients with varicocele stage I--II; the second
      group included 20 patients with varicocele stage III. The ambulatory treatment
      complex permitted the inmprovement of of ultrasound indexes in scrotal veins in
      29 (64%) patients of the 1st group, whereas nobody of the 2nd group showed any
      isignificant improvement. The proper use of the worked out complex allows the
      pathogenetic and correct treatment of varicocele in adolescents.

PMID- 22968503
TI  - [The paraaortic lymphadenectomy with the lower mesenteric artery sceletonization
      for the sigmoid cancer treatment].
AB  - 43 patients with sigmoid cancer stage I--III were operated on. The mean operative
      time was 206.2+/-73.0 min, considering the sceletonization of the lower
      mesenteric artery together with the paraaortic lymphadenectomy took 28+/-9 min.
      The long-term follow-up was performed in all the patients. The median follow-up
      time was 39.35+/-13.1 months. 4 patients had died, 3 of them because of the
      cancer progression. The paraaortic lymphadenectomy with the lower mesenteric
      artery sceletonization is now considered to be the method of choice in treatment
      of sigmoid cancer. The operation is reasonably safe considering the rate of intra
      and postoperative complication rate.

PMID- 22968504
TI  - [The efficacy of the acute pancreatitis' surgical treatment].
AB  - The comparative analysis of blood levels of leukocytes, lymphocytes, the
      leukocytic intoxication index, amylase, lipase, lactatdehydrogenase and
      creatinphosphokinase, measured in operated patients with the acute pancreatitis,
      demonstrated the general positive dynamics of the patients condition. The higher
      blood levels of the substances in died patients demonstrate the important
      prognostic value of them. The higher levels of amylase, lipase,
      lactatdehydrogenase and creatinphosphokinase by the end of the clinical treatment
      together with the normalization of the rest laboratory data may witness the
      higher risk of the chronisation of the pancreatitis.

PMID- 22968505
TI  - [The videoendoscopic sanation of the abdominal cavity by the diffuse septic
      peritonitis].
AB  - The 1st group consisted of 68 patients with the diffuse peritonitis, who were
      treated with the use of traditional approach, i.e., laparotomy, elimination of
      the peritonitis source, nasointestinal intubation, abdominal cavity sanation and
      drainage. Within 24--48 hours all these patients had videoendoscopic abdominal
      sanation with the injection of 200 ml 0.03% water solution of sodium
      hypochlorite. The 2nd group, consisted of 41 patients. The first treatment stage
      was the same, but during the videoendoscopic stage the pulsing stream of the
      antiseptic was used and the procedure ended with intraabdominal injection of 200
      ml 0.03% water solution of sodium hypochlorite immobilized in gel. All patients
      of the 2nd group showed better recovery results.

PMID- 22968506
TI  - [Diagnostics and treatment of the ischemic and reperfusion disorders by the
      intraabdominal ischemic syndrome].
AB  - Ethiology, pathogenesis, treatment and prevention of reperfusion disorders in
      emergency abdominal surgery are highlighted in the article. The thorough analysis
      of reperfusional disorders' pathogenesis by the abdominal compartment syndrome
      was carried out.

PMID- 22968507
TI  - [The comparative characteristics of manual and apparate
      esophagoenteroanastomosis].
AB  - The early and long-term results of 225 gastrectomies, performed on the reason of
      gastric cancer, were analyzed. The comparative analysis of early and long-term
      results showed the statistically significant differences in complication and
      lethality rates between apparate and manual esophagoenteroanastomoses, especially
      considering the rate of reflux-esophagitis.

PMID- 22968508
TI  - [The kidney transplantation from the ABO-incompatible donors].
AB  - The experience of 28 allotransplantations of ABO-incompatible kidneys was
      compared with the treatment results of 38 ABO-compatible renal transplantations.
      The transplanted kidney function, morphological changes of the transplanted
      kidney and the comparative analysis of actuary survival in both groups showed no
      significant difference. The results of the study prove the validity of the kidney
      transplantation from the ABO-incompatible donors.

PMID- 22968509
TI  - [Treatment of the benign obstructive jaundice].

PMID- 22968510
TI  - [The burst of the hydatid cyst into the biliary tree, complicated by the
      choledochduodenal fistula].

PMID- 22968511
TI  - [The spontaneous rupture of the esophagus (the Burhave syndrome)].

PMID- 22968512
TI  - QTLs associated with root traits increase yield in upland rice when transferred
      through marker-assisted selection.
AB  - Altering root morphology of rice (Oryza sativa L.) cultivars could improve yields
      in drought-prone upland ecosystems. Marker-assisted backcross breeding was used
      to introgress four QTLs for root traits into an upland rice cultivar. The QTLs
      had previously been identified under experimental conditions in a different
      genetic background. The introgressed lines and the recurrent parent were grown
      for 6 years by resource-poor farmers in upland sites in Eastern India and yields
      recorded. In combination the QTLs significantly increased yield by 1 t ha(-1)
      under relatively favourable field conditions. In less favourable trials, the QTL
      effects were not detected due to greater heterogeneity in soil-water availability
      in very low yielding environments and consequent yield variability. Root studies
      under controlled conditions showed that lines with the introgressions had longer
      roots throughout tillering than the recurrent parent (14 cm longer 2 weeks after
      sowing). Therefore, both improved roots and increased yield can be attributed to
      the introgression of QTLs. This is the first demonstration that marker-assisted
      backcross breeding (MABC) to introgress multiple root QTLs identified under
      controlled conditions is an effective strategy to improve farmers' yields of
      upland rice. The strategy was used to breed a novel upland rice cultivar that has
      been released in India as Birsa Vikas Dhan 111.

PMID- 22968513
TI  - DNA methylation at differentially methylated regions of imprinted genes is
      resistant to developmental programming by maternal nutrition.
AB  - The nutritional environment in which the mammalian fetus or infant develop is
      recognized as influencing the risk of chronic diseases, such as type 2 diabetes
      and hypertension, in a phenomenon that has become known as developmental
      programming. The late onset of such diseases in response to earlier transient
      experiences has led to the suggestion that developmental programming may have an
      epigenetic component, because epigenetic marks such as DNA methylation or histone
      tail modifications could provide a persistent memory of earlier nutritional
      states. One class of genes that has been considered a potential target or
      mediator of programming events is imprinted genes, because these genes critically
      depend upon epigenetic modifications for correct expression and because many
      imprinted genes have roles in controlling fetal growth as well as neonatal and
      adult metabolism. In this study, we have used an established model of
      developmental programming-isocaloric protein restriction to female mice during
      gestation or lactation-to examine whether there are effects on expression and DNA
      methylation of imprinted genes in the offspring. We find that although expression
      of some imprinted genes in liver of offspring is robustly and sustainably
      changed, methylation of the differentially methylated regions (DMRs) that control
      their monoallelic expression remains largely unaltered. We conclude that
      deregulation of imprinting through a general effect on DMR methylation is
      unlikely to be a common factor in developmental programming.

PMID- 22968514
TI  - Sperm head vacuolization affects clinical outcome in ICSI cycle. A proposal of a
      cut-off value.
AB  - OBJECTIVE: To evaluate the relationship between sperm nuclear vacuoles and sperm
      morphology and to investigate the influence of the rate of spermatozoa with head
      vacuolization (SVR) in a seminal sample on the clinical outcomes in couples
      undergoing intracytoplasmic sperm injection. MATERIALS: 26 patients undergoing
      infertility investigations were included and were divided in two groups according
      to an SVR <= 20,28 % (Group A) or > 20,28 % (Group B), and were investigated to
      verify the influence of SVR on the fertilization rate, embryo quality, pregnancy
      and implantation rates. RESULTS: Abnormal spermatozoa with nuclear vacuoles were
      significantly higher (p < 0.001) than the percentage of normal spermatozoa with
      nuclear vacuoles. Patients in group A had a percentage of abnormal sperm with
      nuclear vacuole significantly lower compared to group B (p < 0,001), but there
      was no difference in the percentage of normal sperm with nuclear vacuoles.
      Fertilization rates and the number of top quality embryos did not differ between
      the two groups. The pregnancy and implantation rates were significantly higher in
      Group A compared to Group B (respectively p < 0,05 and p < 0.001). CONCLUSIONS:
      For the first time, we propose a cut off value in the proportion of sperms with
      nuclear vacuolization on the total of sperm in seminal samples, and demonstrate a
      relationship between SNV and clinical outcomes after ICSI. The SNV rate could be
      introduced as an easy diagnostic evaluation prior to perform an ICSI cycle.

PMID- 22968515
TI  - The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid
      profile in cumulus cells.
AB  - PURPOSE: This research proposed to study the changes in lipid composition in
      cumulus cells (CCs) from women who achieved pregnancy compared with women who did
      not, after in vitro fertilization treatment. This approach has the potential to
      provide novel information on the lipid metabolism of the CCs and as an additional
      method to predict pregnancy. METHOD: Fifty-four samples from couples with tubal
      and male factor infertility and where the female partner was age 35 or younger
      were divided in two groups according to their level of hCG 14 days after embryo
      transfer as follows: (1) 23 samples in pregnant group and (2) 31 samples in non
      pregnant group. Lipid extraction was performed by the Bligh-Dyer protocol, and
      lipid profiles were obtained by MALDI-TOF MS. Mass spectra data were processed
      with MassLynx, and statistical analysis was performed using MarkerLynx extended
      statistic. OPLS-DA model was built. RESULTS: S-plot Analysis revealed three ions
      as potential markers in the pregnant group, and five ions in the non-pregnant
      group. These ions were identified in the human metabolome database (HMDB) as
      phosphatidylcholine in the pregnant group and as phosphatidylethanolamine,
      phosphatidylserine and phosphatidylinositol species in the non-pregnant group.
      These lipids might be involved in cell proliferation and differentiation,
      apoptosis and GAP junction regulation. CONCLUSION: We conclude that MALDI-TOF MS
      can be used as an informative and fast analytical strategy to obtain and study
      the lipid profile of cumulus cells and can potentially be used as a supporting
      tool to predict pregnancy based on the metabolic state of the CCs.

PMID- 22968517
TI  - Preoperative identification of synchronous ovarian and endometrial cancers: the
      importance of appropriate workup.
AB  - OBJECTIVE: For treatment of patients with both endometrial and ovarian cancer, it
      is important to discriminate between 2 primary tumors and metastatic disease.
      Currently, criteria are based on postoperative findings. The aim of this study
      was to determine whether clinical parameters can discriminate between these
      groups preoperatively and whether a practical guideline could improve appropriate
      workup and treatment. METHODS: A total of 45 patients with a diagnosis of both
      endometrium and ovarian cancer between 1998 and 2009 and were included for
      analysis. Clinical and pathological data were obtained, and initial CA-125 was
      registered; patients had a diagnosis of 2 primary tumors or tumors with
      metastasis. All patients were reclassified according to workup and treatment.
      RESULTS: Patients with synchronous primary tumors were significantly younger,
      presented more often with abnormal uterine bleeding, and had a lower initial CA
      125 than both metastatic groups (P < 0.05). With age and CA-125 included in a
      polytomic logistic regression model, 83.3% of diagnoses could be classified
      correctly. In 15 of 17 patients presented with adnexal mass, workup was
      incomplete owing to lack on information of the endometrial status. In patients
      presenting with abnormal uterine bleeding, 13 of 21 patients had an incomplete
      workup leading to staging laparotomy secondary to initial surgical treatment in 2
      patients. CONCLUSIONS: Patients with synchronous endometrial and ovarian cancers
      are young, often present with abnormal uterine bleeding and have a low initial CA
      125. Adequate workup with attention to both ovarian and endometrial status,
      especially in young patients with a wish to preserve fertility, is important to
      make the right decision for treatment.

PMID- 22968518
TI  - Relationship between high density of peritumoral lymphatic vessels and biological
      behavior of cervical cancer.
AB  - OBJECTIVE: To investigate the relationship between lymphangiogenesis and
      lymphatic metastasis in cervical squamous carcinoma. METHODS: Eighty cases of
      invasive cervical squamous cancer were selected as objects of our study. Double
      immunohistochemical staining with antibodies against lymphatic vessel endothelial
      hyaluronan receptor 1 and Ki-67 was used to label the lymphatic vessels and mark
      the proliferative lymphatic vessels in cervical squamous cancer. The peritumoral
      lymphatic vessel density and intratumoral lymphatic vessel density was assessed.
      The lymphatic vessels proliferation index was evaluated by calculating Ki-67
      proliferation index (PI) to reflect the lymphangiogenesis of cervical squamous
      cancer. Then the correlation between lymphangiogenesis and clinicopathologic
      features of cervical squamous cancer was analyzed. RESULTS: The LVD of cervical
      cancer (15.23 +/- 3.6) was clearly higher than that of the adjacent normal
      cervical subepithelial tissues (9.9 +/- 2.5, P < 0.001). The peritumoral
      lymphatic vessel density of cervical cancer (18.75 +/- 4.3) was significantly
      higher than the intratumoral lymphatic vessel density of cervical cancer (11.71
      +/- 4.9, P < 0.001). Lymphatic PI (LPI) of cervical cancer (0.258 +/- 0.07) was
      higher than that of the adjacent normal cervical subepithelial tissues (0.068 +/-
      0.08, P < 0.001). The peritumoral lymphatic vessel PI of cervical cancer (0.324
      +/- 0.06) was notably higher than the intratumoral lymphatic vessel PI of
      cervical cancer (0.232 +/- 0.06, P < 0.001). Peritumoral lymphatic vessel density
      and peritumoral lymphatic vessel were clearly associated with the lymph node
      metastasis (P = 0.001 and P = 0.002, respectively) and lymphovascular space
      invasion (P = 0.024 and P = 0.01, respectively). CONCLUSIONS: The high density of
      peritumoral lymphatic vessels is a potential predictor of more aggressive
      phenotype of cervical squamous cancer.

PMID- 22968516
TI  - CaCl(2) as a bifunctional reusable catalyst: diversity-oriented synthesis of 4H
      pyran library under ultrasonic irradiation.
AB  - CaCl(2) is applied as an efficient reusable and eco-friendly bifunctional
      catalyst for the one-pot three-component synthesis of 4H-pyrans under ultrasonic
      irradiation. A broad range of substrates including the aromatic and
      heteroaromatic aldehydes, indoline-2,3-dione (isatin) derivatives, acenaphthylene
      1,2-dione (acenaphthenequinone) and 2, 2-dihydroxy-2H-indene-1,3-dione
      (ninhydrin) were condensed with carbonyl compounds possessing a reactive alpha
      methylene group and alkylmalonates. All reactions are completed in short times,
      and the products are obtained in good to excellent yields. The catalyst could be
      recycled and reused several times without any loss of efficiency.

PMID- 22968519
TI  - Rare-earth cation effects on three-dimensional metal-organic rotaxane framework
      (MORF) self assembly.
AB  - A set of metal-organic rotaxane frameworks (MORFs) are constructed with the use
      of a tetraimidazolium macrocycle, the terephthalate dianion, and the trivalent
      lanthanide metal cations Nd(III), Sm(III), Eu(III) or Tb(III) and are reported
      herein. The specific choice of the metal cation allows for control of the
      structure and luminescent properties of the resulting molecular frameworks.

PMID- 22968520
TI  - Ultrafast exciton dynamics in InAs/ZnSe nanocrystal quantum dots.
AB  - Colloidal nanocrystal quantum dots with a band gap in the near infra-red have
      potential application as the emitters for telecommunications or in vivo imaging,
      or as the photo-absorbing species in next generation solar cells or
      photodetectors. However, electro- and photoluminescence yields and the efficiency
      with which photo-generated charges can be extracted from quantum dots depend on
      the total rate of recombination, which can be dominated by surface-mediated
      processes. In this study, we use ultrafast transient absorption spectroscopy to
      characterise the recombination dynamics of photo-generated charges in InAs/ZnSe
      nanocrystal quantum dots. We find that recombination is dominated by rapid, sub
      nanosecond transfer of conduction band electrons to surface states. For the size
      of dots studied, we also find no evidence of significant multiple exciton
      generation for photon energies up to 3.2 times the band gap, in agreement with
      our theoretical modelling.

PMID- 22968521
TI  - Teplizumab for treatment of type 1 diabetes mellitus.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of
      teplizumab and evaluate relevant clinical trial data. DATA SOURCES: Searches of
      MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, American
      Diabetes Association scientific posters, and Google Scholar (1966-May 2012) were
      conducted using the key words teplizumab, anti-CD3 monoclonal antibody, MGA031,
      and hOKT3gamma1 (Ala-Ala). Searches were limited to articles published in
      English. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating
      teplizumab for type 1 diabetes mellitus (T1DM) published in English were selected
      from the data sources. All published relevant abstracts were included. References
      cited in identified articles were used for additional citations. DATA SYNTHESIS:
      T1DM accounts for up to 10% of all cases of diabetes mellitus. T1DM is
      characterized as a chronic and progressive autoimmune disease leading to the
      destruction of insulin-producing beta-cells of the pancreas. Teplizumab is a
      humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of the
      T-lymphocytes that mediate the destruction of the insulin-producing beta-cells.
      While clinical data are limited, both Phase 2 and Phase 3 studies have
      demonstrated preserved C-peptide response as a measure of insulin production,
      decreased exogenous insulin use, and improved glycemic control following a 12- to
      14-day teplizumab infusion in patients diagnosed with T1DM within the previous 6
      weeks. However, 1 Phase 3 trial failed to find the same benefits in those
      diagnosed with T1DM within the previous 12 weeks when a lower cumulative
      teplizumab dose was used. Initial studies indicated that teplizumab is well
      tolerated, with a self-limiting rash as the most commonly reported adverse
      effect. CONCLUSIONS: Teplizumab is an anti-CD3 human monoclonal antibody with
      promising activity in treatment of patients with T1DM. Results from Phase 3
      trials are needed to further determine safety, efficacy, and dosing frequency.

PMID- 22968522
TI  - Romidepsin: a histone deacetylase inhibitor for refractory cutaneous T-cell
      lymphoma.
AB  - OBJECTIVE: To evaluate the efficacy and safety of romidepsin in refractory
      cutaneous T-cell lymphoma (CTCL). DATA SOURCES: An English-language literature
      search of PubMed and MEDLINE (Nov 2011-April 2012) was performed using the terms
      romidepsin, CTCL, and depsipeptide (FK228). The National Comprehensive Cancer
      Network guidelines, American Society of Clinical Oncology abstracts, American
      Society of Hematology abstracts, clinical trial registry, and prescribing
      information from the manufacturer were reviewed for additional information. STUDY
      SELECTION AND DATA EXTRACTION: Phase 1 and 2 trials evaluating the efficacy and
      safety of romidepsin were reviewed with a specific focus on its use in cutaneous
      T-cell lymphoma. All peer-reviewed articles with clinically relevant information
      were evaluated for inclusion. DATA SYNTHESIS: In advanced stage CTCL, single or
      combination chemotherapy regimen responses are variable and lack durability.
      Romidepsin is a histone deacetylase inhibitor approved for refractory cutaneous T
      cell lymphoma. Romidepsin has shown an improvement in duration of response and
      pruritus over traditional therapy. In 2 independent Phase 2 trials, romidepsin
      showed an overall response rate of 34% and durable response of 13-15 months in
      patients with refractory CTCL. The most frequent toxicities of romidepsin include
      nausea, vomiting, fatigue, or myelosuppression. Clinically insignificant QT
      interval changes have been observed but did not correlate with a decrease in left
      ventricular ejection fraction, or elevated laboratory markers of myocardial
      damage. CONCLUSIONS: Romidepsin is an effective, durable, and well-tolerated
      single-agent therapy in patients with refractory CTCL and should be considered
      for formulary addition in this population.

PMID- 22968523
TI  - Iron indices and intravenous ferumoxytol: time to steady-state.
AB  - BACKGROUND: The ongoing nature of iron loss in patients receiving hemodialysis
      makes it difficult to maintain adequate iron stores without supplementation. The
      effects of ferumoxytol on iron indices have been measured 35 days after baseline,
      but no study has assessed indices at earlier points in time. OBJECTIVE: To
      evaluate the time to transferrin saturation (TSAT) and ferritin stabilization,
      the point at which TSAT and serum ferritin levels can be accurately measured
      during a 13-treatment period following a loading dose of ferumoxytol. METHODS:
      Ferumoxytol was administered according to the package insert to 15 adults
      undergoing hemodialysis. Vital signs were recorded before treatment, 30 and 60
      minutes after receiving ferumoxytol, and at the end of treatment to monitor for
      adverse reactions and hemodynamic instability. Monitoring continued for a 13
      treatment period (30 days) after drug administration. Blood was collected
      throughout the study to measure TSAT, ferritin, hemoglobin (Hb), and C-reactive
      protein (CRP). RESULTS: TSAT values at 14, 21, and 28 days after drug
      administration were not significantly different from those at 7 days, signifying
      that TSAT values stabilized by day 7. Serum ferritin values at day 14 were
      significantly lower than those 7 days after drug administration (p = 0.028).
      Although serum ferritin values at days 21 and 28 tended to decrease relative to
      values at day 14, the differences were not statistically significant. Therefore,
      it appears that serum ferritin stabilized by day 14 after drug administration.
      Mean (SD) Hb values at screening and at end of the study were 11.7 (1.0) g/dL and
      12.0 (0.9) g/dL, respectively (p = NS). CRP also did not change significantly
      throughout the study period. CONCLUSIONS: Dialysis patients achieve stable iron
      indices quickly. TSAT stabilized by day 7 and ferritin stabilized 14 days after a
      loading dose of ferumoxytol 1 g. Adverse effects were minimal and did not
      necessitate discontinuation of ferumoxytol.

PMID- 22968524
TI  - Effect of dissolved LiCl on the ionic liquid-Au(111) electrical double layer
      structure.
AB  - The electrical double layer at ionic liquid (IL)-Au(111) interfaces is composed
      of alternating ion layers. Interfacial layering is markedly weaker when small
      amounts of LiCl are dissolved in the IL for all potential between -2.0 V and +2.0
      V (vs. Pt). This means that models developed for pure IL electrical double layers
      may not be valid when solutes are present.

PMID- 22968525
TI  - Use of three-dimensional speckle tracking to assess left ventricular myocardial
      mechanics: inter-vendor consistency and reproducibility of strain measurements.
AB  - AIMS: Since there is insufficient data available about the inter-vendor
      consistency of three-dimensional (3D) speckle-tracking (STE) measurements, we
      undertook this study to (i) assess the inter-vendor consistency of 3D LV global
      strain values obtained using two different scanners; (ii) identify the sources of
      inter-vendor inconsistencies, if any; and (iii) compare their respective
      intrinsic variability. METHODS AND RESULTS: Sixty patients (38 +/- 12 years, 64%
      males) with a wide range of LV end-diastolic volumes (from 74 to 205 ml) and
      ejection fractions (from 17 to 70%) underwent two 3D LV data set acquisitions
      using VividE9 and Artida ultrasound systems. Global longitudinal (Lepsilon),
      radial (Repsilon), circumferential (Cepsilon) and area (Aepsilon) strain values
      were obtained offline using the corresponding 3D STE softwares. Despite being
      significantly different, Lepsilon showed the closest values between the two
      platforms (bias = 1.5%, limits of agreement (LOA) from -2.9 to -5.9%, P < 0.05).
      Artida produced significantly higher values of both Cepsilon and Aepsilon than
      VividE9 (bias = 6.6, LOA: -14.1 to 0.9%, and bias = 6.0, LOA = -28.2-8.6%,
      respectively, P < 0.001). Conversely, Repsilon values obtained with Artida were
      significantly lower than those measured using VividE9 platform (bias = -24.2,
      LOA: 1.5-49.9, P < 0.001). All strain components showed good reproducibility
      (intra-class correlation coefficients: 0.82-0.98), except for Repsilon by Artida,
      which showed only a moderate reproducibility. CONCLUSION: Apart from Lepsilon,
      the inter-vendor agreement of Repsilon, Cepsilon and Aepsilon measured with
      Artida and VividE9 was poor. Reference values should be specific for each system
      and baseline and follow-up data in longitudinal studies should be obtained using
      the same 3D STE platform.

PMID- 22968526
TI  - An unexpected quadricuspid aortic valve revealed by multislice computed
      tomography.

PMID- 22968528
TI  - Are the causes of obesity primarily environmental? Yes.

PMID- 22968527
TI  - Effect of tranexamic acid on mortality in patients with traumatic bleeding:
      prespecified analysis of data from randomised controlled trial.
AB  - OBJECTIVES: To examine whether the effect of tranexamic acid on the risk of death
      and thrombotic events in patients with traumatic bleeding varies according to
      baseline risk of death. To assess the extent to which current protocols for
      treatment with tranexamic acid maximise benefits to patients. DESIGN:
      Prespecified stratified analysis of data from an international multicentre
      randomised controlled trial (the CRASH-2 trial) with an estimation of the
      proportion of premature deaths that could potentially be averted through the
      administration of tranexamic acid. PARTICIPANTS: 13,273 trauma patients in the
      CRASH-2 trial who were treated with tranexamic acid or placebo within three hours
      of injury and trauma patients enrolled in UK Trauma and Audit Research Network,
      stratified by risk of death at baseline (<6%, 6-20%, 21-50%, >50%). INTERVENTION:
      Tranexamic acid (1 g over 10 minutes followed by 1 g over eight hours) or
      matching placebo. MAIN OUTCOME MEASURE: Odds ratios and 95% confidence intervals
      for death in hospital within four weeks of injury, deaths from bleeding, and
      fatal and non-fatal thrombotic events associated with the use of tranexamic acid
      according to baseline risk of death. Unless there was strong evidence against the
      null hypothesis of homogeneity of effects (P<0.001), the overall odds ratio was
      used as the most reliable guide to the odds ratios in all strata. RESULTS:
      Tranexamic acid was associated with a significant reduction in all cause
      mortality and deaths from bleeding. In each stratum of baseline risk, there were
      fewer deaths among patients treated with tranexamic acid. There was no evidence
      of heterogeneity in the effect of tranexamic acid on all cause mortality (P=0.96
      for interaction) or deaths from bleeding (P=0.98) by baseline risk of death. In
      those treated with tranexamic acid there was a significant reduction in the odds
      of fatal and non-fatal thrombotic events (odds ratio 0.69, 95% confidence
      interval 0.53 to 0.89; P=0.005) and a significant reduction in arterial
      thrombotic events (0.58, 0.40 to 0.83; P=0.003) but no significant reduction in
      venous thrombotic events (0.83, 0.59 to 1.17; P=0.295). There was no evidence of
      heterogeneity in the effect of tranexamic acid on the risk of thrombotic events
      (P=0.74). If the effect of tranexamic acid is assumed to be the same in all risk
      strata (<6%, 6-20%, 21-50%, >50% risk of death at baseline), the percentage of
      deaths that could be averted by administration of tranexamic acid within three
      hours of injury in each group is 17%, 36%, 30%, and 17%, respectively.
      CONCLUSIONS: Tranexamic acid can be administered safely to a wide spectrum of
      patients with traumatic bleeding and should not be restricted to the most
      severely injured. TRIAL REGISTRATION: ISRCTN86750102.

PMID- 22968529
TI  - Are the causes of obesity primarily environmental? No.

PMID- 22968530
TI  - Using the CUSUM test to control the proportion of inadequate open biopsies of
      musculoskeletal tumors.
AB  - BACKGROUND: Biopsies of musculoskeletal tumors lead to alterations in treatment
      in almost 20% of cases. Control charts are useful to ensure that a process is
      operating at a predetermined level of performance, although their use has not
      been demonstrated in assessing the adequacy of musculoskeletal biopsies.
      QUESTIONS/PURPOSES: We therefore (1) assessed the incidence of and the reasons
      for inadequate musculoskeletal biopsies when following guidelines for performing
      the procedure; and (2) implemented a process control chart, the CUSUM test, to
      monitor the proportion of inadequate biopsies. METHODS: We prospectively studied
      116 incisional biopsies. The biopsy was performed according to 10 rules to (1)
      minimize contamination in the tissues surrounding the tumor; and (2) improve
      accuracy. A frozen section was systematically performed to confirm that a
      representative specimen was obtained. Procedures were considered inadequate if:
      (1) another biopsy was necessary; (2) the biopsy tract was not appropriately
      placed; and (3) the treatment provided based on the diagnosis from the biopsy was
      not appropriate. RESULTS: Five (4.3%) of the 116 incisional biopsy procedures
      were considered failures. Three patients required a second repeat open biopsy and
      two were considered to receive inappropriate treatment. No alarm was raised by
      the control chart and the performance was deemed adequate over the monitoring
      period. CONCLUSIONS: The proportion of inadequate musculoskeletal open biopsies
      performed at a referral center was low. Using a statistical process control
      method to monitor the failures provided a continuous measure of the performance.

PMID- 22968531
TI  - Adult soft tissue sarcoma local recurrence after adjuvant treatment without
      resection of core needle biopsy tract.
AB  - BACKGROUND: Core needle biopsies of sarcomas allow a diagnosis in a high
      percentage of patients with few complications. However, it is unclear whether the
      tract needs to be excised to prevent recurrences. QUESTIONS/PURPOSES: We
      therefore determined the rates of recurrence and metastases in patients with
      Stage III extremity sarcomas, who underwent wide local resection without excision
      of the needle tract and also received adjuvant treatment. METHODS: We
      retrospectively reviewed 59 adult patients with deep, larger than 5 cm, high
      grade soft tissue sarcomas of the upper or lower extremity treated between
      January 1999 and April 2009. All the patients underwent a core needle biopsy.
      Resection was performed with wide margins. The biopsy tract was not resected
      during the definitive surgery. Fifty-seven patients (97%) received preoperative
      and/or postoperative radiation, whereas 49 patients (83%) received chemotherapy.
      Local recurrence and distant recurrence rates were determined. The minimum
      followup was 24 months (median, 56 months; range, 24-122 months). RESULTS: The
      local recurrence rate was 9%. Fifteen patients (25%) developed metastasis after
      diagnosis. Seven of the 59 patients (12%) had microscopic positive margins at
      resection. CONCLUSIONS: Our data demonstrate no increase in local recurrence
      rates or rates of metastatic disease compared with previously published studies
      when resection of the core biopsy tract was not performed. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22968532
TI  - Orthopaedic case of the month: Painless right knee mass in 32-year-old man.

PMID- 22968534
TI  - Predictors of range of motion in patients undergoing manipulation after TKA.
AB  - BACKGROUND: Knee stiffness or limited range of motion (ROM) after total knee
      arthroplasty (TKA) may compromise patient function. Patients with stiffness are
      usually managed with manipulation under anesthesia (MUA) to improve ROM. However,
      the final ROM obtained is multifactorial and may depend on factors such as
      comorbidities, implant type, or the timing of MUA. QUESTIONS/PURPOSES: We asked
      whether diabetes mellitus, implant type, and the interval between TKA and MUA
      influenced post-MUA ROM. METHODS: From a group of 2462 patients with 3224 TKAs
      performed between 1999 and 2007 we retrospectively reviewed 96 patients with 119
      TKAs (4.3%) who underwent MUA. We determined the presence of diabetes mellitus,
      implant type, and the interval between TKA and MUA. RESULTS: The average increase
      in ROM after MUA was 34 degrees . Patients with diabetes mellitus experienced
      lower final ROM after MUA (87.5 degrees  versus 100.3 degrees ) as did patients
      with cruciate-retaining (CR) prostheses versus posterior-stabilized (92.3 degrees
      versus 101.6 degrees ). The interval between TKA and MUA inversely correlated
      with final ROM with a decrease after 75 days. CONCLUSIONS: Most patients
      experience improvements in ROM after MUA. Patients with diabetes mellitus or CR
      prostheses are at risk for lower final ROM after MUA. Manipulation within 75 days
      of TKA is associated with better ROM.

PMID- 22968535
TI  - When do readmissions for infection occur after spine and total joint procedures?
AB  - BACKGROUND: The episode-of-care concept promulgated by the federal government
      requires hospitals to assume the cost burden for all care rendered up to 30 days
      after discharge, including all readmissions occurring in that time. Although
      surgical site infections (SSIs) are a leading cause of readmission after total
      joint arthroplasties (TJA) and spine surgery, it is unclear whether these
      readmissions occur relative to the 30-day period. QUESTIONS/PURPOSES: We
      determined whether (1) most readmissions for SSIs occurred in 30 days, (2) the
      type of procedure performed affected the timing of readmission, and (3) the type
      of infecting organism influenced the timing of readmission. METHODS: From our
      hospital database we identified 91 patients treated with elective TJAs and spine
      surgery from 2007 through 2010 who were readmitted with SSIs. Of the 91 patients,
      46 had undergone spine surgery and 45 had TJAs. For each of these readmissions,
      we determined the type of surgery, the length of time from initial discharge to
      readmission, and the type of infecting organism. RESULTS: Readmissions after
      spine surgery were more likely to occur within 30 days of discharge (80.4% for
      spine, 58.3% for TJAs). In the TJA cohort, there was a trend toward readmissions
      occurring within 30 days of discharge more often in the THA subset. We identified
      no correlation between type of infecting organism and timing of readmission.
      CONCLUSIONS: With the episode-of-care model, SSIs pose a substantial cost burden
      for hospitals since the majority would be included in the 30-day period included
      in the bundled reimbursement.

PMID- 22968536
TI  - Effects of graft quality on non-urgent liver retransplantation survival: should
      we avoid high-risk donors?
AB  - BACKGROUND: Few studies have studied the effects of graft quality on non-urgent
      liver retransplantation (ReLT) outcomes. We aimed to analyze graft
      characteristics and survival in non-urgent ReLT and the effect of using grafts
      with extended criteria on survival. METHODS: Eighty non-urgent ReLT were
      performed from June 1988 to June 2010. The whole series was divided by identical
      time periods to study time-related effects. We assessed graft quality with donor
      risk index (DRI) and Briceno scores and recipient status with the Model for End
      stage Liver Diseases and Rosen scores. Low and high-risk grafts were defined by a
      DRI cutoff of 1.8. RESULTS: Graft survival was similar in both periods (1-, 5-,
      and 10-year graft survivals: 73.5, 46.9, and 40.8 versus 71, 47.7, and 47.7%,
      p=0.935) although donor quality was worse in the second period (DRI: 1.35+/-0.32
      vs. 1.66+/-0.34, p<0.001). In the first period high-risk grafts did worse than
      low-risk grafts (5-year survival: 0 vs. 54.5%, p=0.002) while in the second
      period outcomes were similar (5-year survival: 48.6 vs. 56.7%, p=0.660). Donor
      age was the only independent donor factor for graft survival, with lower survival
      when using grafts from donors over 60-years-old. CONCLUSIONS: Graft quality in
      ReLT has worsened with time mainly because of older donors but nowadays the use
      of high-risk grafts in non-urgent ReLT is not associated with worse graft
      survival because of better perioperative management. Moreover of being selective
      on recipient conditions, care should be taken when using grafts from donors over
      60-years-old for non-urgent ReLT.

PMID- 22968538
TI  - Indians fit the Asian trauma model.

PMID- 22968537
TI  - Incidence and localization of ectopic parathyroid adenomas in previously
      unexplored patients.
AB  - BACKGROUND: Parathyroidectomy has a success rate of >95 % for cure of primary
      hyperparathyroidism. In about 6-16 % of cases, one or more hyperfunctioning
      parathyroid gland(s) are found in an ectopic location. Accurate preoperative
      imaging can aid in detecting these ectopically located glands and allow a focused
      surgical approach with an even higher success rate. The objective of this study
      was to assess the utility of ultrasonography (US) and technetium-99m-sestamibi
      (MIBI) scans in locating ectopic parathyroid glands in previously unexplored
      patients who presented with primary hyperparathyroidism. METHODS: We analyzed a
      total of 1,562 patients who underwent surgery for hyperparathyroidism at our
      institution from 2000 to 2010. Ectopic parathyroid adenomas were identified in
      346 of the patients (22 %). Of the 346 patients, we excluded 144 who underwent
      reoperations, had four-gland hyperplasia or were missing imaging details. We
      carefully reviewed the data, including demographics, laboratory values,
      preoperative localizing imaging details, and operative findings. Preoperative US
      and MIBI results were compared to the intraoperative findings. RESULTS: We
      analyzed 202 patients with ectopic glands for accuracy of preoperative
      localization. Of these 202 patients, a single adenoma was the most common (89 %)
      followed by double adenoma (11 %). The ectopic parathyroid glands were
      predominantly located in the thymus (38 %) followed by 31 % in the
      retroesophageal region; 18 % were intrathyroidal. Preoperative MIBI scans had a
      sensitivity of 89 % (161/197), whereas US had a sensitivity of 59 % (35/63) for
      detecting ectopic glands. Overall, both imaging modalities had a positive
      predictive value of 90 %, with MIBI correctly predicting ectopic glands best in
      the thymus, mediastinum, or the retroesophageal space, and US was most accurate
      at detecting intrathyroidal glands. CONCLUSIONS: Based on the data available at
      our institution, MIBI has a higher sensitivity than US in correctly localizing
      ectopic parathyroid adenomas, but the accuracy of detection varies based on
      location. Both imaging techniques have a high PPV for detecting an ectopic gland.
      Therefore, imaging with MIBI and US can be complementary, and positive
      localization of an ectopic gland with either modality is highly accurate and can
      facilitate a more focused surgical approach.

PMID- 22968539
TI  - Automated generation of libraries of nL droplets.
AB  - We demonstrate an integrated system for rapid and automated generation of
      multiple, chemically distinct populations of ~10(3)-10(4) sub-nanoliter droplets.
      Generation of these 'libraries of droplets' proceeds in the following automated
      steps: i) generation of a sequence of micro-liter droplets of individually
      predetermined composition, ii) injection of these 'parental' droplets onto a
      chip, iii) transition from a mm- to a MUm-scale of the channels and splitting
      each of the parental drops with a flow-focusing module into thousands of tightly
      monodisperse daughter drops and iv) separation of such formed homogeneous
      populations with plugs of a third immiscible fluid. This method is compatible
      both with aspiration of microliter portions of liquid from a 96-well plate with a
      robotic station and with automated microfluidic systems that generate (~MUL)
      droplets of preprogrammed compositions. The system that we present bridges the
      techniques that provide elasticity of protocols executed on microliter droplets
      with the techniques for high-throughput screening of small (~pL, ~nL) droplet
      libraries. The method that we describe can be useful in exploiting the synergy
      between the ability to rapidly screen distinct chemical environments and to
      perform high-throughput studies of single cells or molecules and in digital
      droplet PCR systems.

PMID- 22968540
TI  - Posterior only treatment of adult thoracic kyphosis with multiple Ponte
      osteotomies and pedicle screw instrumentation.

PMID- 22968541
TI  - Revisiting the clinical anatomy of the alar ligaments.
AB  - PURPOSE: The morphology of the alar ligaments has been inconsistently described,
      particularly with regard to the existence of an atlantal portion. Despite these
      inconsistencies, these descriptions have been used to develop physical tests for
      the integrity of these ligaments in patients with cervical spine problems. The
      purpose of this study was to describe the detailed macrostructure of the alar
      ligaments. METHODS: The alar ligaments of 11 cervical spine specimens from
      embalmed adult cadavers were examined by fine dissection. A detailed description
      of the macrostructure of these ligaments and their attachment sites was recorded.
      Measurements were performed with respect to ligament dimensions and relations
      with selected bony landmarks. RESULTS: No atlantal portion of the alar ligament
      was viewed in any specimen. The attachment of the ligaments on the odontoid
      process occurred on its lateral and posterolateral aspects, frequently below the
      level of the apex. The occipital attachment was on the medial surface of the
      occipital condyles in close proximity to the atlanto-occipital joints. The
      orientation of the ligaments was primarily horizontal. The presence of transverse
      bands extending occiput to occiput with minimal or no attachment to the odontoid
      process was a common variant. CONCLUSIONS: The absence of findings with respect
      to the atlantal portion of the alar ligament suggests that it may be considered
      an anatomical variant, not an essential component for stability of the
      craniocervical complex. These findings may inform the use and interpretation of
      clinical tests for alar ligament integrity.

PMID- 22968542
TI  - Commentary on 'disability outcome measures in multiple sclerosis clinical
      trials'.
AB  - In order to fully understand and explore the effectiveness of any intervention
      for the management of multiple sclerosis (MS), it is important to have robust,
      valid, reliable, and universally applied measures. The recent article,
      'Disability outcome measures in multiple sclerosis clinical trials' by Cohen,
      Reingold, Polman and Wolinsky (2012), explores this issue in regards to the
      effective measurement of MS-related disability, and the utilisation of patient
      reported outcome measures, whilst highlighting the need for collaboration between
      the academic and clinical communities. Although it is important to examine
      disability measures, it is also equally important to recognise that physical
      function is only one aspect of a person's experience; for example, quality of
      life and psychological well-being are also important aspects to assess. The
      application of e-health technologies and patient registers could be a useful
      method of gaining additional information, using patient-reported outcomes. This
      commentary explores these issues in relation to points raised by the Cohen et al.
      paper.

PMID- 22968543
TI  - Iron content of the pulvinar nucleus of the thalamus is increased in adolescent
      multiple sclerosis.
AB  - OBJECTIVE: The objective of this paper is to assess abnormal phase values,
      indicative of increased iron content, using susceptibility-weighted imaging (SWI)
      filtered phase of the subcortical deep gray matter (SDGM) in adolescent multiple
      sclerosis (MS) and other neurological disorders (OND) patients, and in healthy
      controls (HC). METHODS: Twenty adolescent MS and eight adolescent OND patients
      and 21 age- and sex-matched HC were scanned on a 3T GE scanner. Mean phase of
      abnormal phase tissue (MP-APT), MP-APT volume, normal phase tissue volume (NPTV)
      and normalized volume measurements were obtained for total SDGM, as well as
      specific structures separately. RESULTS: Significantly increased MP-APT (28.2%,
      p<.001) and MP-APT volume (82.7%, p<.001), and decreased NPTV (-23.3%, p<.001)
      and normalized volume (-15.5%, p<.001) in the pulvinar nucleus of the thalamus
      was found in MS patients compared to HC. MP-APT in MS patients was also increased
      in total SDGM (p=.012) and thalamus (p=.044). Compared to OND patients, MS
      patients had increased MP-APT volume in the pulvinar nucleus of the thalamus
      (p=.044) and caudate (p=.045). Increased MP-APT of the SDGM structures were
      associated with increased T2 and T1 lesion burden and brain atrophy in MS
      patients. CONCLUSION: Adolescent MS patients showed increased iron content in the
      SDGM compared to OND patients and HC.

PMID- 22968544
TI  - Efficacy and safety of beta-interferon in Thai patients with demyelinating
      diseases.
AB  - BACKGROUND: The efficacy of beta-interferon (IFN-beta) treatment in Thai patients
      with demyelinating diseases has not been reported. OBJECTIVES: To evaluate the
      efficacy and any adverse drug reactions of IFN-beta therapy in Thai patients, for
      each group of demyelinating diseases. METHODS: We retrospectively reviewed data
      of Thai patients with multiple sclerosis (MS), neuromyelitis optica (NMO) and NMO
      spectrum disorders (NMOSDs) who attended the MS Clinic at Siriraj Hospital,
      Thailand from March 2000 to October 2011. We reviewed those 73 patients who
      received IFN-beta. We evaluated the drug's efficacy over 2 years and any adverse
      drug reactions among these patients. RESULTS: Of the 40 MS patients who received
      IFN-beta, 26 adhered to the medication for at least 2 years. In addition, 27
      NMO/NMOSDs patients who had been diagnosed with MS were treated as such with IFN
      beta. In the true MS group, the pre- and post-treatment annualized relapse rates
      (ARR) were 1.25 and 0.59, respectively, so there was a reduction of 52.8% (p =
      0.004). In addition, in 69.2% of the patients, IFN-beta also showed beneficial
      effects by prolonging the time to first relapse to 15.9 months and stabilizing or
      decreasing progression of the disease. In contrast, no significant benefit was
      seen in the NMO/NMOSDs group. On the contrary, an increase in EDSS was seen in
      53.3 % of them. The most common side effects seen were local skin reactions and
      flu-like symptoms. CONCLUSIONS: Treatment with IFN-beta was effective in reducing
      both ARR and disability progression in Thai patients with MS. In contrast, we
      observed that giving IFN-beta treatment to NMO/NMOSDs patients may lead to a
      worsening of symptoms.

PMID- 22968545
TI  - Prevalence, demographics and clinical characteristics of multiple sclerosis in
      Qatar.
AB  - No published epidemiologic data on multiple sclerosis (MS) in Qatar exist. Our
      objectives were to determine the prevalence, demographics and clinical
      characteristics of MS in the Middle Eastern country of Qatar. We analyzed data
      for Qatari MS patients fulfilling the McDonald diagnostic criteria. A total of
      154 patients fulfilled the inclusion criteria. On 31 April 2010, the crude
      prevalence of MS in Qatar was 64.57 per 100,000 inhabitants (95% CI: 58.31
      70.37). The female-to-male ratio was 1.33:1. A positive family history was found
      in 10.4% of included MS patients. We conclude that Qatar is now a medium-to-high
      risk area for MS, with some important differences in clinical characteristics as
      compared to other countries in the region.

PMID- 22968547
TI  - Miniaturized transfer models to predict the precipitation of poorly soluble weak
      bases upon entry into the small intestine.
AB  - For poorly soluble weak bases, the possibility of drug precipitation upon entry
      into the small intestine may affect the amount of drug available for uptake
      through the intestinal mucosa. A few years ago, a transfer model was introduced
      which has been developed to simulate the transfer of a dissolved drug out of the
      stomach into the small intestine. However, this setup requires the use of
      clinically relevant doses of the drug, which are typically not available in the
      early stages of formulation development. The present series of tests was
      performed to check whether it is possible to create a miniaturized but
      physiologically relevant transfer model that can be applied in the early
      formulation development. Experiments were performed with two miniaturized setups:
      a 96-well plate model and a mini-paddle transfer system. Itraconazole and
      tamoxifen were used as model drugs. An appropriate amount of each drug
      formulation was dissolved in simulated gastric fluid and then transferred into an
      acceptor phase consisting of fasted/fed state simulated small intestinal fluid.
      The amount of drug dissolved in the acceptor phase was monitored over a period of
      4 h. Results from both setups were very similar. The tamoxifen preformulation did
      not precipitate, whereas the itraconazole formulation precipitated to the same
      extent in both setups. Due to the possibility of generating physiologically
      relevant results but using smaller sample sizes and smaller volumes of media,
      both miniaturized transfer systems offer various advantages in terms of substance
      and analytical and material cost savings when evaluating the precipitation
      potential of poorly soluble weakly basic drug candidates.

PMID- 22968546
TI  - Enhanced dissolution and stability of lansoprazole by cyclodextrin inclusion
      complexation: preparation, characterization, and molecular modeling.
AB  - In this study, lansoprazole (LSP)/cyclodextrin (CD) inclusion complexes were
      prepared using a fluid bed coating technique, with beta-cyclodextrin (beta-CD)
      and 2-hydroxypropyl-beta-cyclodextrin (HPCD) as the host molecules, respectively,
      to simultaneously improve the dissolution and stability of LSP. The dissolution
      rate and stability of LSP was dramatically enhanced by inclusion complexation
      regardless of CD type. LSP/HPCD inclusion complex was more stable under
      illumination than LSP/beta-CD inclusion complex. Differential scanning
      calorimetry and powder X-ray diffractometry proved the absence of crystallinity
      in both LSP/CD inclusion complexes. Fourier transform infrared spectroscopy
      together with molecular modeling indicated that the benzimidazole of LSP was
      included in the cavity of both CDs, while LSP was more deeply included in HPCD
      than beta-CD. The enhanced photostability was due to the inclusion of the
      sulfinyl moiety into the HPCD cavity. CD inclusion complexation could improve the
      dissolution and stability of LSP.

PMID- 22968548
TI  - A novel structural rearrangement reaction of dialkylated derivatives of [Pt2(MU
      S)2(PPh3)4] involving Pt-C bond formation.
AB  - Reaction of [Pt(2)(MU-S)(2)(PPh(3))(4)] with the dialkylating agents
      ClCH(2)C(O)CH(2)Cl or ClCH(2)C(=NNHC(O)NH(2))CH(2)Cl gives the dicationic di-MU
      thiolate complexes [Pt(2){MU-SCH(2)C(O)CH(2)S)(PPh(3))(4)](2+) or [Pt(2){MU
      SCH(2)C(=NNHC(O)NH(2))CH(2)S}(PPh(3))(4)](2+), isolated as BPh(4)(-) salts and
      characterised by ESI mass spectrometry, NMR spectroscopy and single-crystal X-ray
      crystallography. Treatment of the complex [Pt(2){MU
      SCH(2)C(O)CH(2)S)(PPh(3))(4)](2+), which contains a [6.6.4] bicyclic system, with
      hydroxide ions results in deprotonation of a CH(2) group and rearrangement of the
      resulting monocation, giving [Pt(2)(MU-SCH(2)C(O)CHS}(PPh(3))(4)](+), isolated as
      its PF(6)(-) salt. An X-ray structure determination shows the complex to have a
      novel rearranged [6.5.5] bicyclic system containing a Pt-S-Pt-S-C five-membered
      ring with a Pt-C bond. The alkyl ligand has a high trans-influence, manifest in a
      long trans Pt-P bond and small (1)J(PtP) coupling constant to the trans PPh(3)
      ligand. Reaction of [Pt(2)(MU-S)(2)(PPh(3))(4)] with the 2,4
      dinitrophenylhydrazone derivative of 1,3-dichloroacetone leads to the closely
      related complex [Pt(2){MU-SCH(2)C(=NNHAr)CHS}(PPh(3))(3)Cl] [Ar =
      C(6)H(3)(NO(2))(2)] in which a PPh(3) ligand is substituted by a chloride.

PMID- 22968550
TI  - [The microsurgical tissue autotransplantation as a way of local radiation skin
      injuries' treatment].
AB  - The experience of 127 microsurgical autotransplantations of skin-muscular flaps
      in 93 patients with severe radiation skin injuries was analyzed. As free
      revascularized flaps the greater omentum, the skin-muscular thoracodorsal flap,
      the scapular, the radial flap, including flaps with a part of the radial bone,
      the deltoideus, the rotated skin-muscular flap of the abdominal rectus muscle,
      the scapular and/or serratus anterior fascia were used. The transplants'
      acception was registered in all cases. 31 patients demonstrated the development
      of late radiation ulcers during the long term follow up period, requiring further
      dissection and replantation.

PMID- 22968549
TI  - Information filtering by synchronous spikes in a neural population.
AB  - Information about time-dependent sensory stimuli is encoded by the spike trains
      of neurons. Here we consider a population of uncoupled but noisy neurons (each
      subject to some intrinsic noise) that are driven by a common broadband signal. We
      ask specifically how much information is encoded in the synchronous activity of
      the population and how this information transfer is distributed with respect to
      frequency bands. In order to obtain some insight into the mechanism of
      information filtering effects found previously in the literature, we develop a
      mathematical framework to calculate the coherence of the synchronous output with
      the common stimulus for populations of simple neuron models. Within this frame,
      the synchronous activity is treated as the product of filtered versions of the
      spike trains of a subset of neurons. We compare our results for the simple cases
      of (1) a Poisson neuron with a rate modulation and (2) an LIF neuron with
      intrinsic white current noise and a current stimulus. For the Poisson neuron,
      formulas are particularly simple but show only a low-pass behavior of the
      coherence of synchronous activity. For the LIF model, in contrast, the coherence
      function of the synchronous activity shows a clear peak at high frequencies,
      comparable to recent experimental findings. We uncover the mechanism for this
      shift in the maximum of the coherence and discuss some biological implications of
      our findings.

PMID- 22968552
TI  - [Videothoracoscopic treatment of postoperative bleedings and its' complications
      by thoracic traumas].
AB  - 35 patients, operated on the thoracic trauma (ISS - 9+/-3), had videothoracoscopy
      on the reason of the continued bleeding (n=6), clotted hemothorax (n=27) or
      pleura empyem (n=2). The best results were obtained in case of the clotted
      hemothorax thoracoscopic evacuation within 3 days after bleeding. Even the late
      use of videothoracoscopic procedures for the treatment of postoperative
      complications shortens the hospital stay in comparison with the traditional
      methods. The video-assisted thoracoscopic surgery is an accurate and safe method
      for the postoperative bleeding complications in hemodynamically stable patients.

PMID- 22968551
TI  - [The transplantation of revascularized thyroid-trachea-lung complex: the
      experimental study].
AB  - The osteoplastic tracheobronchopathy affects the trachea, main, lobar and smaller
      bronchi, causing their stenosis. Nowadays the mainstay of the treatment of such
      patients is the cryodestruction, laser destruction and the endoscopic buginage of
      the trachea and bronchi. The palliative nature and low efficacy of these
      procedures forces to search new ways of treatment. The traditional lung
      transplantation or separate trachea and lung transplantation is inappropriate
      because of the complex affection of both trachea and bronchi. The experimental
      study aimed the possibility of thyreotracheolung revascularized donor complex
      transplantation.

PMID- 22968553
TI  - [The single-stage surgical treatment of the complicated colon cancer].
AB  - The results of the single-stage surgical treatment of 54 patients with the
      complicated forms of colon cancer were analyzed. All patients had radical
      operations with the formation of primary intestinal anastomosis. For the
      improvement of the results we have optimized the algorithm of the diagnostics and
      treatment of such patients, including the endoscopic colon decompression with its
      recanalization and colic stasis liquidation. The approach to the colon cancer,
      complicated with the intestinal bleeding was also optimized by the use of
      intensive hemostatic and substitutional therapy. The optimal use of the described
      above methods allowed the single-stage radical endosurgical treatment of the
      patients.

PMID- 22968554
TI  - [Surgical treatment of rectocele with the use of mesh implants by the obstructive
      defecation syndrome].
AB  - The aim of current study was to evaluate in complex the effectiveness of
      transvaginal mesh implants in women with obstructed defecation (OD) syndrome
      based on the comparison of preoperative and postoperative results of objective
      diagnostic tools and quality of life parameters. METHODS: from prospectively
      collected database of patients treated in our department those who were treated
      for OD by means of transvaginally placed mesh implants were chosen. The
      comparison of pre- and postoperative results of objective evaluation (prolapse
      stage according to POP-Q system, X-ray defecography - XR-DG and MRI defecography 
      MRI-DG) as well quality of life parameters (Wexner constipation score and
      validated Russian version of King's Health Questionnaire) was undertaken.
      Treatment effectiveness was evaluated using Slinical Global Impression -
      Improvement (CGI-I) i Patient Global Impression - Improvement (PGI-I) scales.
      RESULTS: In 2007-2011 40 women (mean age 51.8+/-10.7 years) underwent
      transvaginal pelvic floor reconstruction with mesh implants. All of them had <=3
      stage pelvic prolapse (POP-Q) and rectocele. Preoperative XR-DG and MRI-DG helped
      reveal rectocele >4 cm in 85 and 43% of women respectively, 68% of patients had
      cystocele and 18% - genital prolapse. In 21 case mesh implants for posterior
      pelvic floor reinforcement were used, in other cases mesh implants for total
      pelvic floor repair were placed. At a mean of 19 months after the operation
      manual examination revealed that 90% of women had 1 stage posterior pelvic
      proplapse, at XR-DG and MRI-DG significant reduction of rectocele size and depth
      of pelvic floor descent was noted. Besides that significant decrease in mean
      values of Wexner constipation score and King's health questionnaire was
      demonstrated. Though mean values of global treatment effectiveness assessment on
      CGI-I and PGI-I scales didn't significantly differ (2.13+/-0.85 i 2.68+/-1.42,
      r=0.06), the rate of agreement between these scales measured at each single case
      was very low (kappa-0.154), this reflects that clinician has more positive
      perception of disease dynamics due to treatment than the patient. When mean
      values of dynamics in different indexes of King's health questionnaire were
      compared it was demonstrated that the index of quality of life influence (3.53+/
      0.96) was significantly higher than the indexes of OD influence (2.63+/-1.08) and
      mechanical symptoms (2.58+/-1.04), this suggests that while the manifestations of
      OD syndrome are significantly improved patient quality of life doesn't change
      substantially. CONCLUSIONS: XR-DG is more specific than MRI-DG in evaluating the
      size of rectocele and the depth of pelvic floor descent; the use of mesh implants
      in surgical treatment of OD syndrome results in significant reduction of
      rectocele and prolapse stage in 90% of patients; clinical evaluation of treatment
      effectiveness based on objective examination is more optimistic than subjective
      perception of treatment results by the patient, this indicates that anatomic
      correction does not always lead to quality of life improvement.

PMID- 22968555
TI  - [The manually assisted laparoscopic surgery of colon cancer].
AB  - The experience of 193 manually assisted laparoscopic operations on the reason of
      colon cancer was analyzed. The mean age of the patients was 63.6+/-11.3 years.
      Men were 85 (44%), women - 108 (56%). The majority of patients had tumor of 2nd
      or 3rd stage. The mean body mass index was 27.6+/-4.6 kg/m2. The conversion was
      needed in 8 (4.1%) cases. There were no intraoperative complications. The
      duration of the manually assisted laparoscopic colon resection was 168+/-45min.
      11 (5.7%) patients had postoperative complications. The thorough analysis of the
      results allow to recommend the method for the treatment of patients with colon
      cancer.

PMID- 22968556
TI  - [The use of Octreotide-depo for the pancreatitis' prophylaxis after radical
      surgery of gastric cancer with lymphadenectomy].
AB  - The efficacy of the medicamentous prophylaxis of the acute postoperative
      pancreatitis (APP) was estimated in 594 patients. They all were divided into 3
      groups: 1st was treated with octreotide, 2nd - with octreotide-depo, 3rd - with 5
      ftoruracil and dalargin. Patients of the 3rd group showed the highest levels of
      alpha-amylase in both blood and drainage fluid during the early postoperative
      period. The frequency and severity of postoperative complication rates were the
      lowest in those patients, who received octreotide-depo and was 3,06%; whereas
      among patients of the 2nd group it was 16,8% and among those, who were treated
      with 5-ftoruracil and dalargin, it was 22,4%. The destructive forms of
      pancreatitis were registered in 2nd and 3rd groups in 1 and 3 patients,
      respectively. Intraabdominal abscesses were registered in 1 patient of the 1st
      and 6 patients of the 3rd group, respectively. The lethality rate was 0.9% in the
      1st group; 1.02% in the 2nd and 1.8% in the 3rd group. The use of somatostatine
      analogues in the prophylaxis of postoperative complications proved to decrease
      overall complications' rate and, first of all, the rate of postoperative
      destructive pancreatitis. The use of the prolonged forms of somatostatine
      analogues, i.e., octreotide depo 10 mg is considered to be highly effective.

PMID- 22968557
TI  - [The requirement for the CT-scan protocol for the proper assessment of pancreatic
      tumors resectability].
AB  - The study aims the determination of the CT-scan protocol for the proper
      assessment of pancreatic tumors respectability. The goal of the CT-scan is a
      proper visualization of the tumor spread onto the surgically important vessels of
      the hepatopancreatobiliary zone and remote metastases verification. The
      diagnostic algorithm of the pancreatic cancer is based on the analysis of the
      variety of cases and diagnostic means.

PMID- 22968558
TI  - [The diagnostics and treatment of the gastrointestinal tract foreign bodies ].
AB  - We have analyzed the results of treatment of 542 patients with the foreign bodies
      of the gastrointestinal tract. 359 of patients were hospitalized. All patients
      were somatically healthy. The majority of the foreign bodies (502 (92.6%)) were
      radio-opaque. 423 (78%) patients had swallowed single foreign body, the rest
      demonstrated multiple substances. In 285 (52.6%) cases the foreign bodies left
      the organism naturally within 7 days. 230 (24%) cases required the endoscopic
      removal. The surgical removal of the foreign body was performed in 25 (4.6%)
      cases.

PMID- 22968559
TI  - [Spleen removal in hematological patients with splenomegaly].
AB  - By large and giant volume of the spleen the mainstay of the surgery remains the
      open splenectomy. Splenomegaly stipulates certain difficulties and dangers of the
      procedure, mainly because the lack of the free space in the abdominal cavity. The
      maximally wide access, preliminary preparation and ligation of the splenic artery
      in situ and thorough separation of the spleen and pancreatic tail provide the
      safety and success of the operation. 374 splenectomies on the reason of the
      splenomegaly were analyzed. The standardization of the technique allowed the 2.5
      times reduction of the postoperative complication rate (from 26.9 to 10.8%); the
      1.8 times reduction of the intraoperative complication rate and the 17% reduction
      of the intraoperative blood loss. The postoperative pancreatitis was registered 4
      times rare; the intraabdominal bleeding - 2 times rare and the frequency of the
      subphrenic abscess was 1.5 times lesser.

PMID- 22968560
TI  - [Treatment of forearm bones pseudarthrosis by the Ilizarov's method].
AB  - The use of the external Ilizarov's ostheosynthesis method with the separate
      control of the radial and ulnar bones allowed the successful consolidation of the
      dysarthrosis and the forearm lengths reconstruction. The method was used in 42
      patients, aged 16-72 years. The long-term follow-up results were obtained in 34
      patients. The excellent results were registered in 24 cases, satisfactory - in 7;
      unsatisfactory - in 3 patients.

PMID- 22968561
TI  - [The influence of Reamberin on the oxidative homeostasis in patients with the
      acute destructive cholecystitis].

PMID- 22968562
TI  - [Influence of new pathogenetic reasonable scheme of complex treatment of
      widespread purulent peritonitis on the course of inflammatory process].
AB  - Efficiency of combined application in complex treatment of widespread purulent
      peritonitis of the metabolic preparation, containing amber acid, inosine,
      riboflavin and nicotineamide, Citoflavin, a preparation of recombinant
      interleukin-2 with intracutaneous way of introduction and a preparation for a
      parenteral nutrition on a basis an omega-3-fat of acids is studied. It is
      established that the usage of the given scheme promotes authentic decrease in the
      maintenance in blood acute phase proteins (CRP, CRP-ultra), inhibitors of tissue
      proteases (alpha1-ATT), markers of endogenous intoxication (midmolecular
      peptides, nitrogen oxide), growth of general phospholipids', thereby reducing
      activity of inflammatory process and stopping it for 5th day of the postoperative
      period.

PMID- 22968563
TI  - [The arrosive bleeding after the closure of the left ventricle wound].

PMID- 22968564
TI  - [The two-stage surgical treatment of the chronic pancreatits, complicated by the
      upper mesenteric artery false aneurism and the recurrent intestinal bleeding].

PMID- 22968565
TI  - [The first experience of the thoracoscopic bronchoplasty on the reason of the
      intermediate bronchus' stenosis in a child].

PMID- 22968566
TI  - Organocatalytic oxidation of aldehydes to mixed anhydrides.
AB  - TEMPO catalyzes the direct oxidation of aldehydes to mixed anhydrides in the
      presence of a carboxylic acid. The anhydrides can be converted in situ to esters,
      secondary, tertiary or Weinreb amides in high yield. Oxidation of the aldehyde
      directly to 2-propyl esters is also possible using only catalytic amounts of
      acid. The oxidation reactions are rapid and take place under mild conditions.

PMID- 22968567
TI  - Effectiveness of implant surface decontamination using a high-pressure sodium
      bicarbonate protocol:  an in vitro study.
AB  - OBJECTIVES: To evaluate the effectiveness of a high-pressure sodium bicarbonate
      spray protocol to decontaminate implant surfaces intentionally inoculated with
      bacteria. MATERIALS AND METHODS: Twenty commercially pure titanium implants, 10
      with machined surfaces and 10 with rough surfaces, were inoculated with
      Streptococcus sanguis and then submitted to a decontamination protocol using a
      high-pressure sodium bicarbonate spray device for 1 minute under aseptic
      conditions. RESULTS: After the application of the decontamination protocol, all
      bacterial cells were removed from the tested implants, regardless of surface
      roughness. CONCLUSION: The results suggest that regardless of the implant surface
      roughness, the protocol using high-pressure sodium bicarbonate spray for 1
      minute, under aseptic conditions, was effective in removing all the viable
      bacterial cells.

PMID- 22968568
TI  - Efficacy of resonance frequency analysis in the diagnosis of compromised bone
      implant interface.
AB  - PURPOSE: To investigate the sensitivity level of resonance frequency analysis
      (RFA) in the identification of contact loss at compromised bone-implant
      interfaces. METHODS: Twelve cylindrical acrylic experimental models housing a
      perpendicularly positioned dental implant were generated. Two different
      compromised bone-implant interfaces to simulate the loss of bone-to-implant
      contact were created in 8 models, whereas the resting 4 simulated the intact
      relationship between implant and bone. Each implant received RFA and subjected to
      serial sectioning to evaluate bone-acrylic interface microscopically. Implant
      stability quotient values were statistically compared among groups. Correlation
      level between the implant stability quotient values and bone-acrylic interface
      conditions was assessed. RESULTS: RFA was not sensitive to recognize the lack of
      horizontal contact (approximately 0.276 mm), but it was able be to discriminate
      the additional loss of approximately 0.1 mm at the bone-implant interface.
      CONCLUSION: RFA is not a reliable method in the assessment of the initial contact
      loss at bone-implant interface.

PMID- 22968569
TI  - Statins, glucocorticoids, and nonsteroidal anti-inflammatory drugs:  their
      influence on implant healing.
AB  - This article aimed at exploring the effects of common systemic medications used
      in the United States and their effects on periimplant bone healing. An electronic
      search for articles evaluating the influence of systemic medications on
      periimplant bone healing was conducted using the PubMed (MEDLINE) database.
      Statins, when administered locally or systemically, were found to increase bone
      formation and density. A reduction in bone turnover and bone-to-implant contact
      was observed in animal models examining the effect of glucocorticoids on
      periimplant bone healing. Continued use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) during or after implant placement was associated with reduced bone-to
      implant contact, bone area, and bone density. Evidence seems to suggest that
      statins improve implant osseointegration. However, glucocorticoids and NSAIDs
      showed conflicting results. Therefore, more randomized clinical trials are needed
      to validate the effect of glucocorticoids and NSAIDs on periimplant bone healing.

PMID- 22968570
TI  - Brisk, pulsatile bleeding from the anterior mandibular incisive canal during
      implant surgery:  a case report and use of an active hemostatic matrix to
      terminate acute bleeding.
AB  - Dental implant surgery in the anterior mandible is considered a relatively
      routine and safe procedure with minimal morbidity. A case of brisk, pulsatile
      bleeding from the anterior mandibular incisive canal and its management using an
      active hemostatic matrix is presented. In addition, a review of the literature
      regarding the anatomy of this region of the mandible and hemostatic strategy to
      achieve hemostasis will be discussed.

PMID- 22968571
TI  - Rehabilitation of the edentulous posterior maxilla after sinus floor elevation
      using deproteinized bovine bone:  a 9-year clinical study.
AB  - OBJECTIVES: To evaluate the long-term survival rate of rough-surfaced implants
      placed in maxillary sinuses augmented with deproteinized bovine bone (Bio-Oss;
      Geistlich Pharma AG, Wolhusen, Switzerland). MATERIALS AND METHODS: Thirteen
      maxillary sinuses were augmented in 10 patients with Bio-Oss. After an average
      healing period of 13.8 months, 24 implants were placed. In 4 cases, biopsies were
      performed and submitted to histological analysis. Clinical and radiographic
      evaluation was performed 9 years after implant placement and minimum 8 years
      after functional loading. RESULTS: At the 9-year control, all the 24 implants
      were still functional. Thus, the implant survival rate was 100%. CONCLUSIONS: Bio
      Oss is an acceptable substitute to the autogenous bone, and it can be used as a
      unique material for sinus floor elevation. Rough-surfaced implants placed in 100%
      Bio-Oss grafts showed a high survival rate (100%) on the long term. Larger
      clinical trials are necessary to confirm our results.

PMID- 22968572
TI  - Predictive factors for maxillary sinus augmentation outcomes:  a case series
      analysis.
AB  - AIM: To determine the influence of different local and systemic factors on
      histologic, histomorphometric, and radiographic outcomes after maxillary sinus
      augmentation. MATERIALS AND METHODS: Fifty-two sinus augmentation procedures were
      performed. Grafting material consisted of a mixture of anorganic bovine bone
      (ABB) and autogenous bone. After 6 months, bone core biopsies were harvested from
      implant sites for histologic and histomorphometric analyses. Data regarding age,
      gender, type of edentulism, alcohol consumption, smoking habits, and history of
      periodontal disease were recorded and statistically analyzed. RESULTS:
      Histomorphometric analyses revealed the presence of 35.75% +/- 16.42% of vital
      bone, 40.56% +/- 16.23% of nonmineralized tissue, and 23.69% +/- 18.23% of
      residual ABB particles. Radiographic vertical bone resorption inversely
      correlated with residual ABB. A significant difference in bone resorption
      patterns was observed for completely edentulous patients and for those with a
      history of periodontitis. Tobacco and alcohol negatively influenced vital bone
      formation after sinus augmentation. Implant and prostheses survival after 2 years
      of functional loading was not directly affected by patient's individual habits.
      CONCLUSION: Certain patient-related variables such as history of periodontitis,
      type of edentulism, or smoking/drinking habits play an important role in bone
      graft maturation after maxillary sinus floor elevation.

PMID- 22968573
TI  - Evaluation of patients' perceptions of alterations after chin bone graft
      harvesting.
AB  - OBJECTIVE: To evaluate patients' perceptions of alterations occurring after chin
      bone harvesting. MATERIALS AND METHODS: Thirty patients were evaluated
      subjectively by visual analog scale-related sensitivity, facial aesthetics,
      eating, speaking, and lower lip movement, during 12 months. Objective analysis
      used the static light touch neurosensorial test. The statistical analysis was
      executed with Friedman test with P < 0.05 for both samples. RESULTS: Subjective
      analysis revealed no alterations (1) to facial aesthetics, eating, speaking or
      lower lip movement but sensitivity of the mental region went from a lot of
      alteration initially (5) to little at the end of the study (3). Objective
      analysis results showed normal sensitivity (1) in the region after 12 months.
      CONCLUSION: The discrepancy between subjective and objective analyses may be
      indicative of the limited precision of clinical testing for subjective
      impressions assessment.

PMID- 22968574
TI  - The biological aging of titanium implants.
AB  - Despite the substantial contribution of titanium implants in the field of dental
      and orthopedic reconstructive therapy, there is a crucial unaddressed question of
      why bone-implant contact does not reach the ideal 100%. This review article
      introduces the recently reported time-dependent reduction in osteoconductivity
      and other biological capabilities of titanium since processing. This phenomenon
      is defined as the biological aging of titanium and provides insight to
      significantly advance the understanding of osseointegration and to further
      improve implant surfaces in the future.

PMID- 22968575
TI  - Sinus bone grafting technique using special reamers and microelevators.
AB  - When residual bone height is insufficient in the maxillary posterior area, the
      maxillary sinus elevation and implant placement with lateral approach are
      oftentimes used. However, the risk of sinus membrane perforation, or tearing, is
      high for this procedure. This article introduces a technique that uses a special
      reamer and a microelevator to minimize sinus membrane injury.

PMID- 22968577
TI  - Planarized B-phenylborataanthracene anions: structural and electronic impacts of
      coplanar constraint.
AB  - Potassium and lithium salts of anionic B-phenylborataanthracenes, whose phenyl
      groups were fixed in a coplanar fashion, were synthesized. These compounds
      exhibited solvent-separated ion pair structures both in the crystalline state and
      in solution. Planarization of the phenyl moiety had a remarkable impact on the
      photophysical properties, such as the red-shifted absorption and intense
      fluorescence.

PMID- 22968576
TI  - Parenting stress in Chinese mothers of children with autism spectrum disorders.
AB  - OBJECTIVE: Elevated parenting stress has been observed among mothers of children
      with autism spectrum disorders (ASDs) in western countries, but little is known
      about mothers of Han Chinese children. The aim of the current study was to
      further the knowledge about stress experienced by Chinese mothers of children
      with ASD by examining maternal parenting stress in Heilongjiang province of
      China. METHODS: In this cross-sectional study, data about participants'
      demographic characteristics, parenting stress, anxiety, depression, child's
      behavioral problems, coping strategies, and social support were collected though
      a questionnaire survey. The participants included 150 families with ASD children,
      who were consecutively admitted to the clinics of the Children Development and
      Behavior Research Center in Harbin Medical University, Heilongjiang Disabled
      Persons Federation, and Mudanjiang Child Welfare Home. RESULTS: The participants
      reported elevated parenting stress. Mothers' parenting stress was associated with
      levels of depression and anxiety, and child's behavioral symptoms. Child's
      behavioral symptoms, maternal anxiety, maternal depressive symptoms, and lack of
      governmental financial support were associated with overall parenting stress.
      CONCLUSIONS: Government support may play an important role in reducing parenting
      stress in this population.

PMID- 22968579
TI  - Graphene on metallic surfaces: problems and perspectives.
AB  - The present manuscript summarizes the modern view on the problem of the graphene
      metal interaction. Presently, the close-packed surfaces of d metals are used as
      templates for the preparation of highly-ordered graphene layers. Different
      classifications can be introduced for these systems: graphene on lattice-matched
      and graphene on lattice-mismatched surfaces where the interaction with the
      metallic substrate can be either "strong" or "weak". Here these classifications,
      with the focus on the specific features in the electronic structure in all cases,
      are considered on the basis of large amount of experimental and theoretical data,
      summarized and discussed. The perspectives of the graphene-metal interfaces in
      fundamental and applied physics and chemistry are pointed out.

PMID- 22968578
TI  - Fetal fibronectin (Quick Check fFN test((r))) for detection of premature rupture
      of fetal membranes.
AB  - OBJECTIVES: This study was designed to detect the accuracy of the fetal
      fibronectin (Quick Check fFN test((r))) in diagnosing premature rupture of fetal
      membranes. STUDY DESIGN: This comparative prospective study was carried out over
      1 year in Ahmadi Kuwait Oil Company (KOC) Hospital, Kuwait from March 2011 till
      March 2012. PATIENTS AND METHODS: Two hundred and twenty (220) pregnant women >34
      and <37 weeks gestation were included in this study and divided into two groups
      according to presence or absence of PROM; 110 patients with PROM were included in
      group I, and 110 patients without PROM were included in group II as controls.
      Patients with multiple pregnancies or >37 weeks gestation or not sure of dates or
      fetal distress or vaginal bleeding or preterm labor or chorioamnionitis were
      excluded from this study. The diagnosis of PROM was based on patient's history of
      sudden gush of water, pooling of amniotic fluid, positive ferning pattern,
      positive nitrazine test, confirmed by visualization of fluid passing from the
      cervical canal during sterile speculum examination and Trans-abdominal ultrasound
      to measure the amniotic fluid index (AFI <= 5 cm in PROM). The gestational age
      was calculate from the first day of LMP and confirmed by early ultrasound scan
      (done before 20 weeks gestation). Patients included in this study were subjected
      to standard examination, trans-abdominal ultrasound and sterile speculum
      examination to detect amniotic fluid pooling through the cervical canal and for
      collection of samples on admission. Some laboratory investigations were done to
      exclude chorioamnionitis (maternal fever, maternal tachycardia, fetal
      tachycardia, maternal leucocytosis, CRP). RESULTS: In this study, the sensitivity
      and the specificity of fetal fibronectin in diagnosing PROM were 94.5 and 89.1 %,
      respectively, as compared with 84.5 % sensitivity and 78.2 % specificity for
      Ferning test, respectively, and 87.3 % sensitivity and 80.9 % specificity for
      Nitrazine test, respectively. The PPV and NPV of fetal fibronectin were 89.7 and
      94.2 %, respectively, as compared with 79.5 % PPV and 83.5 % NPV for Ferning
      test, respectively, and 82.1 % PPV and 86.4 % NPV for Nitrazine test,
      respectively. Fetal fibronectin was more accurate (91.8 %) for detection of PROM
      than Ferning (81.4 %) or Nitrazine (84.1 %) tests. CONCLUSION: The Quick Check
      fFN test((r)) for detection of the fetal fibronectin in the vaginal fluid is a
      simple bedside test, more sensitive, and specific than Ferning and Nitrazine
      tests, it can be used as complimentary test to confirm the clinical diagnosis of
      premature rupture of fetal membranes.

PMID- 22968580
TI  - Greater risk of parkinsonism associated with non-N370S GBA1 mutations.
AB  - Mutations in beta-glucosidase (GBA1) are the most common genetic risk factor for
      Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1)
      in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations
      and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study
      aimed to determine the comparative risk of parkinsonism in individuals who are
      affected or carriers of Gaucher disease (GD) and to ascertain the influence of
      different GBA1 mutations on risk/clinical expression. We conducted a secondary
      analysis of cross-sectional data assessing the prevalence of parkinsonism in a
      population of GD1 patients and their heterozygote and non-carrier family members.
      Two logistic regression models, both employing a family-specific random effect,
      were used to assess (1) the association between GBA1 mutation (N370S or non
      N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between
      GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81),
      8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those
      greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1
      (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14).
      Among GBA1 heterozygotes, non-N370S mutations were associated with a
      significantly increased risk of parkinsonism compared to N370S (OR = 22.5; p =
      0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was
      associated with a non-significant two-fold increased risk of parkinsonism. GBA1
      heterozygotes with non-N370S mutations associated with Gaucher disease have an
      increased risk of parkinsonism compared to those with N370S mutations.

PMID- 22968583
TI  - New insights into creatine transporter deficiency: the importance of recycling
      creatine in the brain.

PMID- 22968582
TI  - Heparan sulfate derived disaccharides in plasma and total urinary excretion of
      glycosaminoglycans correlate with disease severity in Sanfilippo disease.
AB  - BACKGROUND: Sanfilippo disease (Mucopolysaccharidosis III) is a neurodegenerative
      lysosomal disorder characterized by accumulation of the glycosaminoglycan heparan
      sulfate (HS). MPS III has a large phenotypic variability and early assessment of
      disease severity is difficult. We investigated the correlation between disease
      severity and the plasma concentration of HS (pHS, defined by the sum of the
      heparan sulfate derived disaccharides obtained after enzymatic digestion) and
      urinary total GAGs level (uGAGs, measured by the dimethylene blue test) in a
      cross-sectional cohort of 44 MPS III patients. METHODS: Disease severity was
      established on the basis of the age of complete loss of independent walking and
      of full loss of speech in all patients. Hazard ratios (HR) were obtained with cox
      regression analysis. In order to allow prediction of a severe phenotype based on
      a cut-off value for pHS, patients were divided in two groups (severely affected
      and less severely affected) based on predictive mutations or on the age of full
      loss of speech. Receiver operator characteristics (ROC) were obtained for pHS.
      RESULTS: pHS and uGAGs were independently and linearly associated with an
      increased risk of speech loss with a HR of 1.8 (95 % CI 1.3-2.7) per 500 ng/ml
      increase of HS in plasma (p = 0.002), and a HR of 2.7 (95 % CI 1.6-4.4) per 10
      mg/mmol creatinine increase of uGAGs (p < 0.001). pHS and uGAGS were less
      strongly associated with loss of walking. The area under the ROC curve for pHS
      was 0.85, indicating good discrimination. CONCLUSION: pHS and uGAGs may be useful
      biomarkers for prediction of severity in MPS III.

PMID- 22968581
TI  - Comparative binding, endocytosis, and biodistribution of antibodies and antibody
      coated carriers for targeted delivery of lysosomal enzymes to ICAM-1 versus
      transferrin receptor.
AB  - Targeting lysosomal enzymes to receptors involved in transport into and across
      cells holds promise to enhance peripheral and brain delivery of enzyme
      replacement therapies (ERTs) for lysosomal storage disorders. Receptors being
      explored include those associated with clathrin-mediated pathways, yet other
      pathways seem also viable. Well characterized examples are that of transferrin
      receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1), involved in iron
      transport and leukocyte extravasation, respectively. TfR and ICAM-1 support ERT
      delivery via clathrin- vs. cell adhesion molecule-mediated mechanisms, displaying
      different valency and size restrictions. To comparatively assess this, we used
      antibodies vs. larger multivalent antibody-coated carriers and evaluated TfR vs.
      ICAM-1 binding and endocytosis in endothelial cells, as well as in vivo
      biodistribution and delivery of a model lysosomal enzyme required in peripheral
      organs and brain: acid sphingomyelinase (ASM), deficient in types A-B Niemann
      Pick disease. We found similar binding of antibodies to both receptors under
      control conditions, with enhanced binding to activated endothelium for ICAM-1,
      yet only anti-TfR induced endocytosis efficiently. Contrarily, antibody-coated
      carriers showed enhanced binding, engulfment, and endocytosis for ICAM-1. In
      mice, anti-TfR enhanced brain targeting over anti-ICAM, with an opposite outcome
      in the lungs, while carriers enhanced ICAM-1 targeting over TfR in both organs.
      Both targeted carriers enhanced ASM delivery to the brain and lungs vs. free ASM,
      with greater enhancement for anti-ICAM carriers. Therefore, targeting TfR or ICAM
      1 improves lysosomal enzyme delivery. Yet, TfR targeting may be more efficient
      for smaller conjugates or fusion proteins, while ICAM-1 targeting seems superior
      for multivalent carrier formulations.

PMID- 22968584
TI  - Synthesis, structure and molecular modelling of anionic carbosilane dendrimers.
AB  - Anionic carbosilane dendrimers of generations 1-3 have been synthesized
      containing carboxylate G(n)X(C(2)H(4)CO(2)Na)(m) and sulfonate
      G(n)X(C(2)H(4)SO(3)Na)(m) peripheral groups and derived from two different cores,
      1,3,5-(HO)(3)C(6)H(3) (X = O(3)) and Si(C(3)H(5))(4) (X = Si). The peripheral
      anionic groups make these dendrimers water soluble, despite their highly
      hydrophobic framework. These dendrimers present a net negative charge in water,
      which was influenced by the pH of the medium. This characteristic was studied by
      pH titration. Also molecular modeling calculations have been performed to study
      differences in an aqueous medium between carboxylate and sulfonate dendrimers of
      different cores. The results obtained were also compared with those obtained from
      DOSY NMR experiments and zeta-potential measurements.

PMID- 22968585
TI  - Kinetic modeling of solvent-free lipase-catalyzed partial hydrolysis of palm oil.
AB  - This work reports the experimental data and kinetic modeling of diacylglycerol
      (DAG) production from palm oil using a commercial immobilized lipase (Lipozyme RM
      IM) in a solvent-free medium. The experiments were performed in batch mode, at 55
      degrees C and 400 rpm, and the effects of enzyme concentration (0.68-2.04 wt%
      related to the mass of substrates), initial water concentration (5-15 wt% related
      to the mass of oil), and reaction time were evaluated. A novel kinetic model is
      presented based on the ordered-sequential bi-bi mechanism considering hydrolysis
      and esterification steps, in which a correlation between water-in-oil solubility
      and surfactant molecules concentration in the oil allowed the model to describe
      the induction period in the beginning of the hydrolysis reaction. Moreover, mass
      transfer limitations related to the enzyme concentration in the system were also
      taken into account. The proposed model presented a very satisfactory agreement
      with the experimental data, thus allowing a better understanding of the reaction
      kinetics. The best conditions obtained for the product (partially hydrolyzed palm
      oil) in terms of DAG yield (35.91 wt%) were 2.87 wt% enzyme/substrate, 2.10 wt%
      water/oil, and 72 h of reaction.

PMID- 22968586
TI  - Lipase-catalyzed synthesis of cocoa butter equivalent from palm olein and
      saturated fatty acid distillate from palm oil physical refinery.
AB  - Cocoa butter equivalent was prepared by enzymatic acidolysis reaction of
      substrate consisting of refined palm olein oil and palmitic-stearic fatty acid
      mixture. The reactions were performed in a batch reactor at a temperature of 60 
      degrees C in an orbital shaker operated at 160 RPM. Different mass ratios of
      substrates were explored and the compositions of the five major triacylglycerol
      (TAG) of the structured lipids were identified and quantified using cocoa butter
      certified reference material IRMM-801. The reaction resulted in production of
      cococa butter equivent with TAG compostion (POP 26.6 %, POS 42.1, POO 7.5, SOS
      18.0 %, and SOO 5.8 %) and melting temperature between 34.7 and 39.6  degrees C
      which is close to that of the cocoa butter. The result of this research
      demonstrated the potential use of saturated fatty acid distillate (palmitic and
      stearic fatty acids) obtained from palm oil physical refining process into a
      value-added product.

PMID- 22968587
TI  - Synthesis and preliminary in vitro biological evaluation of 5-chloro-2
      (substituted phenyl)benzo[d]thiazole derivatives designed as novel
      antimelanogenesis agents.
AB  - We describe the design, synthesis, and biological activities of 5-chloro-2
      (substituted phenyl)benzo[d]thiazole derivatives as novel tyrosinase inhibitors.
      Among them, 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol
      (MHY884) and 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl)phenol (MHY966) showed
      inhibitory activity higher than or similar to kojic acid, against mushroom
      tyrosinase. Therefore, we carried out kinetic studies on the two compounds with
      potent tyrosinase inhibitory effects. Kinetic analysis of tyrosinase inhibition
      revealed that all of these compounds are competitive inhibitors. MHY884 and
      MHY966 effectively inhibited tyrosinase activity and reduced melanin levels in
      B16 cells treated with alpha-melanocyte stimulating hormone (alpha-MSH). These
      data strongly suggest that the newly synthesized compounds MHY884 and MHY966
      could suppress production of melanin via inhibition of tyrosinase activity.

PMID- 22968588
TI  - Chicken egg yolk antibody (IgY) controls Solobacterium moorei under in vitro and
      in vivo conditions.
AB  - Solobacterium moorei is a causative agent in diseases such as oral halitosis,
      bacteremia, and necrobacillosis-associated thrombophlebitis. The objective of
      this study was to determine the effectiveness of chicken egg yolk antibody (IgY)
      in controlling S. moorei. Intact S. moorei cells were used as an immunogen to
      immunize four White Leghorn laying hens. IgY, extracted from egg yolks obtained
      from these immunized hens, was purified using water dilution, two-step salt
      precipitation, and ultrafiltration. The purity of the IgY obtained was
      approximately 87.3 %. The antibody titer of the IgY was determined by enzyme
      linked immunosorbent assay. The antibody titer peaked at 10,000 following the
      third immunization. In order to evaluate the inhibitory effects of the specific
      IgY, the growth of S. moorei in liquid media was measured every 12 h using a
      microplate reader at 600 nm. Biofilm formation of S. moorei was quantified by
      staining with crystal violet. The specific binding ability of IgY was further
      confirmed by the use of immunofluorescence and immunoelectron microscopy. Growth
      and biofilm formation of S. moorei were significantly (P<0.05) inhibited by 20
      and 40 mg/ml specific IgY compared with the control. The specific IgY also
      decreased the bacterial level in the oral cavity of mice after infection with S.
      moorei. This study demonstrates that the growth and biofilm formation of S.
      moorei can be effectively inhibited by specific IgY. As a result, IgY technology
      may have application in the control of diseases caused by S. moorei.

PMID- 22968589
TI  - Effects of SPORL and dilute acid pretreatment on substrate morphology, cell
      physical and chemical wall structures, and subsequent enzymatic hydrolysis of
      lodgepole pine.
AB  - The effects of pretreatment by dilute acid and sulfite pretreatment to overcome
      recalcitrance of lignocellulose (SPORL) on substrate morphology, cell wall
      physical and chemical structures, along with the subsequent enzymatic hydrolysis
      of lodgepole pine substrate were investigated. FE-SEM and TEM images of substrate
      structural morphological changes showed that SPORL pretreatment resulted in fiber
      separation, where SPORL high pH (4.2) pretreatment exhibited better fiber
      separation than SPORL low pH (1.9) pretreatment. Dilute acid pretreatment
      produced very poor fiber separation, consisting mostly of fiber bundles. The
      removal of almost all hemicelluloses in the dilute acid pretreated substrate did
      not overcome recalcitrance to achieve a high cellulose conversion when lignin
      removal was limited. SPORL high pH pretreatment removed more lignin but less
      hemicellulose, while SPORL low pH pretreatment removed about the same amount of
      lignin and hemicelluloses in lodgepole pine substrates when compared with dilute
      acid pretreatment. Substrates pretreated with either SPORL process had a much
      higher cellulose conversion than those produced with dilute acid pretreatment.
      Lignin removal in addition to removal of hemicellulose in SPORL pretreatment
      plays an important role in improving the cellulose hydrolysis of the substrate.

PMID- 22968590
TI  - Flocculating property of extracellular polymeric substances produced by a biofilm
      forming bacterium Acinetobacter junii BB1A.
AB  - Extracellular polymeric substances (EPS) produced by a biofilm-producing
      bacterium Acinetobacter junii BB1A were characterized. Purified EPS on analysis
      revealed neutral sugar (73.21 %), uronic acid (10.12 %), amino sugars (0.23 %),
      alpha- amino acids (11.13 %), and aromatic amino acids (1.23 %). Infrared
      spectrometry revealed the presence of hydroxyl, carboxyl, and amide groups. The
      average molecular weight of the polysaccharide (PS) fraction of EPS was ~2*10(5).
      Gas liquid chromatography analysis of PS revealed the presence of three main
      sugar residues, namely, mannose, galactose, and arabinose (molar ratio of 3:1:1).
      Cation-independent flocculation above 90 % was observed in the pH range of 4-5
      with EPS dosage of 30 mgl(-1) at 20  degrees C. The emulsifying activity of EPS
      was 66.6 % with toluene, 60 % with n-hexadecane, 53.3 % with olive oil, and least
      activity of 13.3 % with kerosene. Proteinase K- and trichloroacetic acid-treated
      EPS showed reduction in flocculation and emulsification, suggesting the
      significant role of protein component. Energy dispersive X-ray spectroscopy was
      used to provide direct evidence of biosorption of Co(II), Cd(II), and Hg(II) by
      EPS.

PMID- 22968591
TI  - An efficient and reproducible method for in vitro clonal multiplication of
      Rauvolfia tetraphylla L. and evaluation of genetic stability using DNA-based
      markers.
AB  - An efficient protocol is described for the rapid in vitro clonal propagation of
      an endangered medicinal plant, Rauvolfia tetraphylla L., through high frequency
      shoot induction from nodal explants collected from young shoots of a field grown
      plant. Effects of growth regulators [6-benzyladenine (BA), kinetin (Kin) 2iP, or
      alpha-naphthalene acetic acid (NAA)], carbohydrates, different medium [Murashige
      and Skoog (MS), Woody Plant Medium (WPM), Gamborg medium (B5), Linsmier and Skoog
      medium (LS)], and various pH levels on in vitro morphogenesis were investigated.
      The highest frequency of shoot regeneration (90 %) and maximum number of shoot
      (35.4 +/- 2.3) per explant were observed on WPM medium supplemented with 7.5 MUM
      BA, 2.5 MUM NAA, and 30 g/l sucrose at pH 5.8. Well-developed shoots, 4-5 cm in
      length, were successfully rooted ex vitro at 90 % by a 30-min pulse treatment
      with 150 MUM IBA prior to their transfer in planting substrates. The survival
      rate of transplantation reached 90 % when transferred to field condition. Genetic
      stability of micropropagated plantlets was assessed and compared with mother
      plant using Random Amplified Polymorphic DNA and Inter Simple Sequence Repeats
      markers. No variation was observed in DNA fingerprinting patterns among the
      micropropagated plants, which were similar to that of the donor plant
      illustrating their genetic uniformity and clonal fidelity. This confirms that
      clonal propagation of this plant using axillary shoot buds can be used for
      commercial exploitation of the selected genotype where a high degree of fidelity
      is an essential prerequisite. The work contributed to a better in vitro
      regeneration and clonal mass multiplication of R. tetraphylla and to develop a
      strategy for the germplasm conservation of this endangered medicinal plant.

PMID- 22968592
TI  - Expanding 3D geometry for enhanced on-chip microbubble production and single step
      formation of liposome modified microbubbles.
AB  - Micron sized, lipid stabilized bubbles of gas are of interest as contrast agents
      for ultra-sound (US) imaging and increasingly as delivery vehicles for targeted,
      triggered, therapeutic delivery. Microfluidics provides a reproducible means for
      microbubble production and surface functionalisation. In this study, microbubbles
      are generated on chip using flow-focussing microfluidic devices that combine
      streams of gas and liquid through a nozzle a few microns wide and then subjecting
      the two phases to a downstream pressure drop. While microfluidics has
      successfully demonstrated the generation of monodisperse bubble populations,
      these approaches inherently produce low bubble counts. We introduce a new micro
      spray flow regime that generates consistently high bubble concentrations that are
      more clinically relevant compared to traditional monodisperse bubble populations.
      Final bubble concentrations produced by the micro-spray regime were up to 10(10)
      bubbles mL(-1). The technique is shown to be highly reproducible and by using
      multiplexed chip arrays, the time taken to produce one millilitre of sample
      containing 10(10) bubbles mL(-1) was ~10 min. Further, we also demonstrate that
      it is possible to attach liposomes, loaded with quantum dots (QDs) or
      fluorescein, in a single step during MBs formation.

PMID- 22968593
TI  - Novel glycine-dependent inactivation of NMDA receptors in cultured hippocampal
      neurons.
AB  - OBJECTIVE: Glycine acts as a co-agonist for the activation of N-methyl-D
      aspartate receptors (NMDARs) by binding to glycine sites, thus potentiating
      glutamate-elicited responses and inhibiting NMDAR desensitization in a dose
      dependent manner. The present study aimed to characterize the glycine-dependent
      inactivation of NMDARs and to explore its pathophysiological significance.
      METHODS: Primary hippocampal cell cultures from embryonic days 17-18 rats were
      treated with NMDA or NMDA plus glycine. Patch-clamp recording and intracellular
      Ca(2+) imaging were performed to test the effects of glycine on NMDA-activated
      currents and increase of intracellular free Ca(2+) respectively.
      Immunofluorescence staining was conducted to examine NR1 internalization. Cell
      damage was tested with MTT method and lactate dehydrogenase leakage. RESULTS:
      Glycine reduced the peak current and Ca(2+) influx elicited by NMDA application
      at concentrations >= 300 MUmol/L. This is a novel suppressive influence of
      glycine on NMDAR function, since it occurs via the NMDAR glycine-binding site, in
      contrast to the classic suppression, which occurs through the binding of glycine
      to glycine receptors. The level of membrane NMDARs was measured to evaluate
      whether internalization was involved. Immunohistochemical labeling showed that
      incubation with high concentrations of NMDA plus glycine did not change the
      expression of NMDARs on the cell surface when compared to the expression without
      glycine; hence the possibility of NMDAR internalization primed by glycine binding
      was excluded. CONCLUSION: In summary, the novel suppressive effect of glycine on
      NMDARs was mediated via binding to the glycine site of the NMDAR and not by
      activation of the strychnine-sensitive glycine-receptor-gated chloride channel or
      by the internalization of NMDARs. The inhibitory influence of glycine on NMDARs
      adds a new insight to our knowledge of the complexity of synaptic transmission.

PMID- 22968594
TI  - Neuronal autophagy in cerebral ischemia.
AB  - Autophagy has evolved as a conserved process for the bulk degradation and
      recycling of cytosolic components, such as long-lived proteins and organelles. In
      neurons, autophagy is important for homeostasis and protein quality control and
      is maintained at relatively low levels under normal conditions, while it is
      upregulated in response to pathophysiological conditions, such as cerebral
      ischemic injury. However, the role of autophagy is more complex. It depends on
      age or brain maturity, region, severity of insult, and the stage of ischemia.
      Whether autophagy plays a beneficial or a detrimental role in cerebral ischemia
      depends on various pathological conditions. In this review, we elucidate the role
      of neuronal autophagy in cerebral ischemia.

PMID- 22968596
TI  - Microwave ablation of pulmonary malignancies using a novel high-energy antenna
      system.
AB  - PURPOSE: To evaluate the technical success, safety, and imaging follow-up of
      malignant pulmonary nodules treated with a novel high-energy percutaneous
      microwave ablation (MWA) system. METHODS: Between July 2010 and September 2011, a
      total of 23 patients, 12 men, mean age 68 (range 30-87) years with 29 pulmonary
      malignancies of median diameter 19 (range 8-57) mm, underwent computed tomography
      (CT)-guided MWA with a 16G microwave needle antenna enabling power up to 180 W.
      Technical success was defined as needle placement in the intended lesion without
      death or serious injury. Adequacy of ablation was assessed at 24 h on contrast
      enhanced CT. Circumferential solid or ground glass opacification >5 mm was used
      to define an ideal ablation. Local tumor recurrence was assessed at 1, 3, and 6
      months after ablation on contrast-enhanced CT. RESULTS: MWA was technically
      successful in 93 % (n = 27). Mean ablation duration was 3.6 (range 1-9) min. Ten
      patients (43 %) developed a pneumothorax as a result of the MWA; only 3 (13 %)
      required placement of a chest drain. Thirty-day mortality rate was 0 %. The mean
      hospital stay was 1.5 (range 1-7) days. A total of 22 lesions (75 %) were
      surrounded by >=5 mm ground glass or solid opacification after the procedure. At
      a median follow-up of 6 months, local recurrence was identified in 3 out of 26
      lesions, giving a local control rate of 88 %. CONCLUSION: MWA using a high-power
      antenna of pulmonary malignancies is safe, technically achievable, and enables
      fast ablation times.

PMID- 22968595
TI  - Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The
      pathology of AD includes amyloid-beta (Abeta) deposits in neuritic plaques and
      neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal
      loss in specific brain regions. Increasing epidemiological and functional
      neuroimaging evidence indicates that global and regional disruptions in brain
      metabolism are involved in the pathogenesis of this disease. Abeta precursor
      protein is cleaved to produce both extracellular and intracellular Abeta,
      accumulation of which might interfere with the homeostasis of cellular
      metabolism. Mitochondria are highly dynamic organelles that not only supply the
      main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction
      might contribute to Abeta neurotoxicity. In this review, we summarize the
      pathways of Abeta generation and its potential neurotoxic effects on cellular
      metabolism and mitochondrial dysfunction.

PMID- 22968597
TI  - Determining early adhesion of cells on polysaccharides/PCL surfaces by a quartz
      crystal microbalance.
AB  - The early adhesions of cells to various biopolymers are important to their
      growths and proliferations. Here, the adhesion of cells (e.g., fibroblasts) on
      the electrode of a quartz crystal microbalance (QCM) that was coated by PCL or
      PEG/PCL and further adsorbed by chitosan (CS) or CS/hyaluronic acid (HA) layers,
      was examined by cell-counting technique, QCM method and MTS assay under a serum
      free condition for 3 h. The surfaces on electrodes of the QCM were confirmed to
      have been modified by measuring their contact angles, FT-IR spectra and the
      weights of biopolymers affected the frequency shifts of the QCM. Among tested
      surfaces on electrodes, the adhesion of fibroblasts on a HA/CS/PCL surface was
      the most (e.g., 3.08 * 10(5) cells/cm(2)) while that on a PEG/PCL surface was the
      least (e.g., 0.7 * 10(5) cells/cm(2)), as determined by cell-counting technique.
      The frequency shift and the mass of adhering fibroblasts on HA/CS/PCL electrodes
      were -3,537 +/- 770 Hz and 3.78 +/- 0.22 MUg (n = 3), respectively, that were
      significantly exceeded those on other electrodes (-393 +/- 58 Hz and 0.32 +/-
      0.06 MUg, n = 3, respectively, for PEG/PCL electrodes). These results were
      consistent with cell-counting technique. Although MTS assay yielded similar
      results, it was less sensitive than the two aforementioned methods. In
      conclusion, modified electrodes of a QCM provide a convenient and sensitive
      method for examining the early adhesion of cells (e.g., 3 h) to biopolymer
      surfaces.

PMID- 22968598
TI  - The posterior medial cortex is involved in visual but not in verbal memory
      encoding processing: an intracerebral recording study.
AB  - The objective is to study the involvement of the posterior medial cortex (PMC) in
      encoding and retrieval by visual and auditory memory processing. Intracerebral
      recordings were studied in two epilepsy-surgery candidates with depth electrodes
      implanted in the retrosplenial cingulate, precuneus, cuneus, lingual gyrus and
      hippocampus. We recorded the event-related potentials (ERP) evoked by visual and
      auditory memory encoding-retrieval tasks. In the hippocampus, ERP were elicited
      in the encoding and retrieval phases in the two modalities. In the PMC, ERP were
      recorded in both the encoding and the retrieval visual tasks; in the auditory
      modality, they were recorded in the retrieval task, but not in the encoding task.
      In conclusion, the PMC is modality dependent in memory processing. ERP is
      elicited by memory retrieval, but it is not elicited by auditory encoding memory
      processing in the PMC. The PMC appears to be involved not only in higher-order
      top-down cognitive activities but also in more basic, rather than bottom-up
      activities.

PMID- 22968600
TI  - Multinuclear palladium(II) complexes from P-C and P-Cl bond cleavage in
      (R(P),R(P)/S(P),S(P))-[PdCl2{1,2-(P(t)BuCl)2C2B10H10}].
AB  - Two multinuclear palladium(II) complexes have been isolated as decomposition
      products resulting from P-Cl and P-C bond cleavage in (R(P),R(P)/S(P),S(P))
      [PdCl(2){1,2-(P(t)BuCl)(2)C(2)B(10)H(10)}] in dichloromethane.

PMID- 22968601
TI  - Nacnac(Bn)CuOiPr: a strained geometry resulting in very high lactide
      polymerization activity.
AB  - N,N'-Dibenzyl diketiminate copper isopropanolate, (nacnac(Bn)CuOiPr)(2),
      polymerizes rac- and S,S-lactide in the presence or absence of isopropanol as a
      chain-transfer reagent with very high activity (k(2) = 32 M(-1) s(-1)), narrow
      polydispersities and without evidence of side reactions such as
      transesterification, epimerization or catalyst decomposition.

PMID- 22968599
TI  - Rasagiline and selegiline, inhibitors of type B monoamine oxidase, induce type A
      monoamine oxidase in human SH-SY5Y cells.
AB  - Type B monoamine oxidase (MAO-B) is proposed to be involved in the pathogenesis
      of neurodegenerative disorders, such as Parkinson's disease, through oxidative
      stress and synthesis of neurotoxins. MAO-B inhibitors, rasagiline and selegiline
      [(-)deprenyl], protect neuronal cells by direct intervention in mitochondrial
      death signaling and induction of pro-survival Bcl-2 and neurotrophic factors.
      Recently, type A MAO (MAO-A) was found to mediate the induction of anti-apoptotic
      Bcl-2 by rasagiline, whereas MAO-A increases in neuronal death and also serves as
      a target of neurotoxins. These controversial results suggest that MAO-A may play
      a decisive role in neuronal survival and death. This paper reports that
      rasagiline and selegiline increased the mRNA, protein and catalytic activity of
      MAO-A in SH-SY5Y cells. Silencing MAO-A expression with small interfering (si)RNA
      suppressed rasagiline-dependent MAO-A expression, but MAO-B overexpression in SH
      SY5Y cells did not affect, suggesting that MAO-A, not MAO-B, might be associated
      with MAO-A upregulation. Rasagiline reduced R1, a MAO-A specific repressor, but
      selegiline did not. Mithramycin-A, an inhibitor of Sp1 binding, and actinomycin
      D, a transcriptional inhibitor, reduced the rasagiline-dependent upregulation of
      MAO-A mRNA, indicating that rasagiline induced MAO-A transcriptionally through R1
      Sp1 pathway, whereas selegiline by another non-defined pathway. These results are
      discussed in relation to the role of MAO-A and these MAO-B inhibitors in neuronal
      death and neuroprotection.

PMID- 22968602
TI  - [State of lower alveolar and mental nerves by mandible fractures healing under
      transbone osteosynthesis].
AB  - Fracture of mandibular body at the level of P3-P4 with symphysis rupture was
      modeled, reposition and transosseous osteosynthesis with a specially developed
      device were performed under anesthesia in the operating room in 17 adult mongrel
      dogs in order to specify the pathogenesis and the dynamics of injury and jaw
      nerve regeneration. It has been established, that the arrangement of the
      neurovascular bundle in medullary canal predetermines the development of acute
      and chronic compression-and-ischemic neuropathy even if accurate reposition of
      bone fragments takes place. The histological signs of nerve fiber regeneration,
      the loss of the quantity of myelin-free nerve conductors and the retrograde
      spreading of degenerative changes in myelinized nerve conductors, including
      regenerating ones, have been found beginning from 4 weeks after injury. It has
      been concluded, that spontaneous nerve regeneration in case of mandibular
      fractures should be actively supported by neuroprotective, anti-edematous and
      anti-inflammatory therapy.

PMID- 22968603
TI  - [Mandible reparative regeneration and adaptive remodeling by multiply fracture
      treatment by means of transbone osteosynthesis].
AB  - Mandibular injuries are the most common pathology of the facial skeleton. The aim
      of the study was to substantiate the effectiveness of treatment of this pathology
      using transosseous osteosynthesis method from the experimental and morphological
      point of view. The bone union of mandibular fragments has been confirmed
      experimentally in 27 adult mongrel dogs after a month of fixation by the device
      and within a month after its demounting. The functionally adequate fibrous and
      connective union has been formed in the zone of mandibular junction rupture in
      the same periods.

PMID- 22968604
TI  - [Ultramicroscopic evaluation of teeth enamel de- and remineralization].
AB  - The paper presents the results of scanning electronic microscopy evaluation of
      teeth enamel surface. The method allows studying objects at huge magnification
      and without preliminary preparation. Research was conducted in vitro on extracted
      teeth. Morphological features of tooth enamel were studied, as well as changes of
      enamel surface after application of remineralization agent.

PMID- 22968605
TI  - [Enamel structure of atypically formed human teeth].
AB  - Using light and scanning electron microscopy thin epoxide processed sections of
      12 impacted third molars, one molar developed in odontogenic follicular cyst and
      one tooth-like teratoma were studied. It was established that the 4 impacted
      teeth and the tooth developed in odontogenic follicular cyst had obvious signs of
      enamel damage in the form of erosion in the crown fissures. The features of
      enamel alteration make it possible to interpret the changes as carious process
      which apparently has endogenous origin. Tooth-like teratoma extracted from
      ovarian dermoid cyst looked like canine and incisor "hybrid" coronal portion of
      which is covered with thin enamel layer, marked by obvious signs of multiple
      erosive lesions of endogenous nature. But unlike alterations in impacted teeth it
      resembles either fluorosis or enamel hypoplasia.

PMID- 22968606
TI  - [In vitro comparison of antibacterial properties of antiseptics used in
      periodontology].
AB  - Antibacterial properties of antiseptics most commonly used in periodontology were
      examined in vitro showing al agents containing chlorhexidine to be the most
      effective against gram-negative (E. coli), gram-positive (staphylococcus,
      streptococcus, enterococcus) germs as well as a C. albicans.

PMID- 22968607
TI  - [Dental services in bronchial asthma patients and the ways to improve them].
AB  - The study was conducted in 783 bronchial asthma patients which have been
      established to need treatment of caries and its complications in 95.4+/-0.84% of
      cases. The received data suggest that it is possible to achieve a highly
      efficient treatment of caries and its complications in patients suffering from
      bronchial asthma in out-patient clinical conditions.

PMID- 22968608
TI  - [Halitosis in certain somatic diseases].
AB  - The structure of exhaled air at various somatopathies is evaluated in the study.
      Presence and concentration of hydrogen sulfide, dimethilsulfide, putrescine,
      cadaverine in patients with otolaryngological, endocrine pathology, diseases of
      gastrointestinal tract and oral diseases. The obtained data is of great
      importance for halitosis causes diagnostics.

PMID- 22968609
TI  - [Treatment of halitosis with mouth rinsing agents containing essential oils].
AB  - The main reason for halitosis is the enhanced evaporable amount of sulphur
      compounds in the exhalation, which originates in the oral cavity due to local
      protein fission. Oral bacteria hydrolyze proteins and further degrade amino
      acids, which leads to halitosis. In an alkaline environment, many bacterial
      species found in the oral cavity with their enzymes participate in the
      degradation of proteins and formation of evaporable sulphur compounds. The
      presence of bacteria in the oral cavity is associated with different chronic
      inflammations in the soft tissues of the oral cavity. Mouth rinsing agents, which
      contain essential oils, ensure the renewal of a normal microbiota in the oral
      cavity, decreases the quantitative amount of bacteria and products released by
      proteolytic bacteria. Bad breath was confirmed by measurements made by a portable
      sulphide monitor or halimeter (Interscan Corporation, Model RH-17E USA). The
      halimeter quantifies breath measurements in parts-per-billion (ppb) of sulphur
      compounds. Halimeter measurements of patients showed increased levels of sulphur
      compounds. Oral mouthwashes containing essential oils possess a typical
      antimicrobial activity, apparently, they do not form resistant microorganism
      strains, and they do not cause allergic reactions.

PMID- 22968610
TI  - [Oral fluid bacteriocidal activity in complex diagnostics of oral disbiosis].
AB  - The possibility of examination of oral fluid bacteriocidal activity in complex
      diagnostics of oral mucosa disbiosis was evaluated. Thirty-seven patients were
      included in complex clinical and laboratory studies. The patients were divided in
      two groups: main group (30 patients exhibiting various grades of oral mucosa
      disbiosis) and control group (7 patients with no signs of oral disbiosis). The
      oral fluid bacteriocidal activity was examined by means of laser flow cytometry.
      Study results proved oral fluid bacteriocidal activity increase to correlate with
      the grade of oral mucosa disbiosis thus confirming the usefulness of the method
      in complex diagnostics of oral disbiosis.

PMID- 22968611
TI  - [Clinical evaluation of the effectiveness of manual toothbrushes with different
      brush field characteristics].
AB  - Nowadays an individual selection of personal care depending on the dental and
      hygiene human status is of great importance. The present study examines the
      clinical efficacy of toothbrushes with different characteristics of the brush
      field. The cleaning efficiency of toothbrushes with horizontal slant bristle and
      smooth cutting of the brush field is 75%, toothbrushes with a horizontal slant
      bristle and multilevel cutting of the brush field - 79%, toothbrushes with power
      bulge - 70% and toothbrushes with a flat brush field - 56%.

PMID- 22968612
TI  - [Treatment method of patients with chronic recurred mandibular dislocation].
AB  - Original method treatment of patients with chronic recurred mandibular
      dislocation is offered. Limitation of oral opening within the bounds of
      physiology was made with nailon ligature which jointed mandible with malar bone.
      The operation is effective, simple and may be done in out-patient conditions
      under local anesthesia.

PMID- 22968613
TI  - [Fundoscopic vessel examination in patients with severe maxillofacial phlegmons].
AB  - Using the fundoscopic vessels examination in patients with odontogenic phlegmon
      it was found out that in severe infectious disease of maxillofacial area the
      vascular figure is significantly changed. These changes confirm the growing brain
      swelling with intracranial hypertension as a result of heavy CNS intoxication.

PMID- 22968614
TI  - [Incidence and mortality of dental diseases in patients with hematological
      disorders].
AB  - The study was conducted in 102 patients with hematological disorders admitted to
      the Research Center of Hematology. It was concluded that more than 50% of them
      needed oral surgery procedures requiring multidisciplinary approach.

PMID- 22968615
TI  - [Clinical efficiency of cytokines in prophylactics and treatment of infectious
      and inflammatory complications after oral surgery procedures].
AB  - The study presents the results of prevention and treatment of infectious and
      inflammatory complications after oral surgery procedures. Combined therapy with
      antibiotics and superlimf promotes a more rapid reduction in the duration of
      clinical symptoms and duration of treatment than monotherapy with antibiotics.
      Results of the study substantiate the feasibility of using superlimf in
      outpatient oral surgical procedures for infectious and inflammatory complications
      treatment.

PMID- 22968616
TI  - [Tongue structure, position and function in cleft lip and palate children
      assessed by ultrasound examination].
AB  - The aim of the study was to examine the position and function of the tongue in
      cleft lip and palate (CLP) patients and to reveal their impact on alveolar bone
      development. Two hundred and fifty-eight CLP children and 50 healthy children as
      control group were included in the study. Tongue function and position were
      assessed by ultrasound examination. In CLP patients the dorsum of the tongue was
      deformed and the asymmetry of some tongue structures was also found out (mainly
      the massive of the tongue muscles). Low tip and high dorsum position were
      specific for CLP children as well as discoordinated tongue movements. Both in
      static and dynamic condition the tongue was pressed to the lower alveolar bone
      thus disturbing its development. The obtained data showed tongue position and
      function to be one of the causes for lower promacrognathy and lingual inclination
      of incisors in CLP patients. The absence of tongue impact on the upper alveolar
      bone should be seen as one of the factors for upper retromicrognathy.

PMID- 22968617
TI  - [Changes of gingival groove microbiosis by orthodontic treatment].
AB  - Gingival groove and dental plaque microbiosis was studied for 6 months in
      patients receiving orthodontic treatment. The patients were divided in two groups
      according to the type of used toothbrushes (manual or electric). After fixation
      of orthodontic appliances the increase of S. epidermidis by simultaneous decrease
      of E. faecium was observed in both groups. This shift was overcome one month
      later. Electric toothbrush showed better effectiveness for dental hygiene in
      patients with fixed orthodontic appliances.

PMID- 22968618
TI  - [The theoretical substantiation of myofunctional correction of sagittal occlusion
      abnormalities and temporomandibular joint dysfunction].
AB  - Simulation in 3D-model of skeletal forms of sagittal malocclusion revealed
      tendency in tonus' modification of muscles of mastication in formation of distal
      and mesial occlusion. It's shown that distal occlusion is characterized by
      hypotonic condition of muscles of mastication, except posterior fibers of
      temporal muscle. Mesial occlusion is characterized by complex combination of
      muscle tone with prevalence of hypotonic condition of anterior fibers of temporal
      muscle, superficial portion of masseter muscle and medial pterygoid muscle. We
      have detected that using of myofunctional devices in treatment of sagittal
      malocclusion, temporomandibular joint dysfunction promotes of tone increasing of
      muscles of mastication.

PMID- 22968619
TI  - Initiator-lightened polymers: preparation of end-functionalized polymers by ATRP
      and their intramolecular charge transfer and aggregation-induced emission.
AB  - A simple strategy to prepare AIE polymers is invented using an AIE initiator for
      atom transfer radical polymerization. The dual photoresponse by intramolecular
      charge-transfer and luminogen aggregation of the initiator is well-realized and
      even enlarged after polymerization, due to the linkage of polymer chains.

PMID- 22968620
TI  - The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and
      ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and
      abscisic acid receptor gene activities.
AB  - Plants perceiving drought activate multiple responses to improve survival,
      including large-scale alterations in gene expression. This article reports on the
      roles in the drought response of two Arabidopsis thaliana homeodomain-leucine
      zipper class I genes; ATHB7 and ATHB12, both strongly induced by water-deficit
      and abscisic acid (ABA). ABA-mediated transcriptional regulation of both genes is
      shown to depend on the activity of protein phosphatases type 2C (PP2C). ATHB7 and
      ATHB12 are, thus, targets of the ABA signalling mechanism defined by the PP2Cs
      and the PYR/PYL family of ABA receptors, with which the PP2C proteins interact.
      Our results from chromatin immunoprecipitation and gene expression analyses
      demonstrate that ATHB7 and ATHB12 act as positive transcriptional regulators of
      PP2C genes, and thereby as negative regulators of abscisic acid signalling. In
      support of this notion, our results also show that ATHB7 and ATHB12 act to
      repress the transcription of genes encoding the ABA receptors PYL5 and PYL8 in
      response to an ABA stimulus. In summary, we demonstrate that ATHB7 and ATHB12
      have essential functions in the primary response to drought, as mediators of a
      negative feedback effect on ABA signalling in the plant response to water
      deficit.

PMID- 22968622
TI  - Geometrical requirements for transition-metal-centered aromatic boron wheels: the
      case of VB10(-).
AB  - A class of transition-metal-centered aromatic boron wheels (D(nh)-M(c)B(n)(q-))
      have been recently produced and characterized according to an electronic design
      principle. Here we investigate the interplay between electronic and geometric
      requirements for the molecular wheels using the case of VB(10)(-), which is
      isoelectronic to the decacoordinated molecular wheels, Ta(c)B(10)(-) and
      Nb(c)B(10)(-). Photoelectron spectra of VB(10)(-) are observed to be broad and
      complicated with relatively low electron binding energies, in contrast to the
      simple and high electron binding energies observed for the molecular wheels of
      its heavier congeners. An unbiased global minimum search found the most stable
      isomer of VB(10)(-) to be a singlet "boat"-like structure (C(2)), in which the V
      atom is coordinated to a quasi-planar B(10) unit. A similar triplet C(2v) boat
      like isomer is found to be almost degenerate to the C(2) structure, whereas the
      beautiful molecular wheel structure, D(10h)-V(c)B(10)(-), is significantly higher
      in energy on the potential energy surface. Therefore, even though the VB(10)(-)
      system fulfills the electronic requirement to form a D(10h)-M(c)B(10)(-) aromatic
      molecular wheel, the V atom is too small to stabilize the ten-membered boron
      ring.

PMID- 22968621
TI  - Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor
      AU-rich mRNA-binding protein.
AB  - Tristetraprolin (TTP) is a RNA-binding protein that inhibits the expression of
      pro-inflammatory cytokines and invasiveness-associated genes. TTP levels are
      decreased in many different cancer types and it has been proposed that this
      protein could be used as a prognostic factor in breast cancer. Here, using
      publicly available DNA microarray datasets, "serial analysis of gene expression"
      libraries and qRT-PCR analysis, we determined that TTP mRNA is present in normal
      breast cells and its levels are significantly decreased in all breast cancer
      subtypes. In addition, by immunostaining, we found that TTP expression is higher
      in normal breast tissue and benign lesions than in infiltrating carcinomas. Among
      these, lower grade tumors showed increased TTP expression compared to higher
      grade cancers. Therefore, these data indicate that TTP protein levels would
      provide a better negative correlation with breast cancer invasiveness than TTP
      transcript levels. In mice, we found that TTP mRNA and protein expression is also
      diminished in mammary tumors. Interestingly, a strong positive association of TTP
      expression and mammary differentiation was identified in normal and tumor cells.
      In fact, TTP expression is highly increased during lactation, showing good
      correlation with various mammary differentiation factors. TTP expression was also
      induced in mammary HC11 cells treated with lactogenic hormones, mainly by
      prolactin, through Stat5A activation. The effect of this hormone was highly
      dependent on mammary differentiation status, as prolactin was unable to elicit a
      similar response in proliferating or neoplastic mammary cells. In summary, these
      studies show that TTP expression is strongly linked to the mammary
      differentiation program in human and mice, suggesting that this protein might
      play specific and relevant roles in the normal physiology of the gland.

PMID- 22968623
TI  - Injury incidence in a sports school during a 3-year follow-up.
AB  - PURPOSE: This study prospectively analysed sports injury incidence over 3 seasons
      in a regional sports school within an injury surveillance project, involving 372
      athletes (12-19 years) from 16 different disciplines. METHODS: A personal sports
      diary was used to record all sporting activities daily for every athlete.
      Injuries (time-loss definition) were registered via a standardized questionnaire.
      RESULTS: Sports injury incidence (injuries/1,000 h) evolved from 3.9 in the first
      year to 4.8 in the second (p < 0.01) and down to 2.8 in the third (p < 0.001,
      compared to the preceding periods). Significant decreases of injury incidence in
      the third year were also observed when classifying injuries as traumatic or
      overuse, and as new or recurrent. The proportion of recurrent injuries was lower
      in the third period (11 %) when compared to the first (19.5 %, p < 0.05) and the
      second one (26.3 %, p < 0.05). Injury incidence was lowest during the third
      period for all severity categories. The same was found when considering injuries
      within racket, team and individual sports. CONCLUSIONS: Implementing an injury
      surveillance system in this setting was associated with a lower injury incidence
      in the third observation period. This project may have influenced stakeholders'
      awareness and attitude towards the sports injury problematic.

PMID- 22968624
TI  - Biomechanical evaluation of the side-cutting manoeuvre associated with ACL injury
      in young female handball players.
AB  - PURPOSE: The purpose of the study was to investigate the biomechanics of the knee
      and hip joint during handball-specific side-cutting on the dominant and non
      dominant leg. Understanding the sports-specific biomechanics may improve
      prevention measures and post-injury treatment. METHODS: Twenty-four young female
      elite handball players performed 5 handball side-cutting manoeuvres on the
      dominant and non-dominant legs. The local maxima of the joint moments in each
      plane, during the initial 100 ms following foot contact, were collected. RESULTS:
      External knee moments of flexion, outward rotation and valgus-along with external
      hip moments of extension, abduction and internal rotation-were observed,
      coincidentally 30-40 ms after foot contact. No side-to-side asymmetries were
      found. The external moments observed support the injury mechanisms previously
      described in case studies of handball injuries. CONCLUSION: The results underline
      the importance of implementing preventive exercises that increase activity of
      medial hamstrings, to match the external outward rotating knee moments and knee
      valgus moments, and increase activity of hip external rotators to match the
      external hip inward-rotating moment. Furthermore, the results may yield further
      information to the graft selection decision before ACL surgery. LEVEL OF
      EVIDENCE: Diagnostic studies, Level II.

PMID- 22968625
TI  - Effects of mineral supplementation on liver cirrhotic/cancer male patients.
AB  - The aim of the present study was to compare the levels of essential trace and
      toxic elements in biological samples (blood and serum) of male liver
      cirrhotic/cancer patients (n = 144), of age groups 30-50 years, before and after
      60 days treatment with mineral supplementation. For comparison purposes, the same
      biological samples were also collected from healthy male subjects (n = 120) of
      the same age groups. The biological samples were oxidized by 65 % HNO3/30 % H2O2
      (2:1) in a microwave oven. The digests of all biological samples were analyzed
      for arsenic (As), cadmium (Cd), selenium (Se), and zinc (Zn) by electrothermal
      atomic absorption spectrometry. The levels of Se and Zn were lower in liver
      cirrhotic/cancer patients as compared to healthy individuals (p < 0.001). The
      patients with liver cirrhosis/cancer have twofold higher As and Cd levels in
      biological samples as compared to age-matched referents. Moreover, a negative
      correlation was observed between essential and toxic elements. The pathogenesis
      of liver cirrhosis/cancer has been associated with changes in the balance of
      certain essential trace and toxic elements. The study confirms that oral
      supplements of Se and Zn produce metabolic effects in patients with liver
      cirrhosis/cancer. It was observed that the status of essential trace elements, Se
      and Zn, was improved in biological samples of all patients after 60 days of
      treatment with mineral supplementation.

PMID- 22968626
TI  - Phase III randomized trial of toremifene versus tamoxifen for Japanese
      postmenopausal patients with early breast cancer.
AB  - BACKGROUND: Toremifene, a selective estrogen receptor modulator, is used as
      adjuvant therapy for postmenopausal patients with breast cancer in Japan. For
      Japanese patients, however, only limited data are available on the efficacy and
      safety profile of toremifene. To establish the long term efficacy and safety of
      toremifene for Japanese patients, we conducted a prospective, multicenter,
      randomized phase III trial comparing toremifene and tamoxifen. PATIENTS AND
      METHODS: The subjects were postmenopausal Japanese patients who had undergone
      surgery for node-negative breast cancer. Toremifene or tamoxifen was administered
      for 2 years. The primary endpoint was demonstration of the non-inferiority of
      toremifene compared with tamoxifen in respect of 5-year survival. Secondary
      endpoints were cumulative overall survival, cumulative disease-free survival,
      effects on lipid profiles, and adverse events. RESULTS: A total of 253 patients
      were enrolled. The baseline characteristics of the two treatment groups were well
      balanced. Median follow-up was 66.5 months. Five-year survival was similar for
      toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1),
      indicating that toremifene is not inferior to tamoxifen for postmenopausal
      Japanese patients with early breast cancer. Cumulative overall survival and
      cumulative disease-free survival were also very similar for toremifene and
      tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank
      test P = 0.3359, respectively). Adverse events in both groups were similar and
      mostly mild or moderate. Thus, both are equally effective and well tolerated.
      CONCLUSION: Our results suggest that the efficacy and safety of toremifene and
      tamoxifen are equivalent for postmenopausal Japanese patients with early breast
      cancer.

PMID- 22968627
TI  - Two cases of primary small cell carcinoma of the breast showing non-mass-like
      pattern on diagnostic imaging and histopathology.
AB  - Primary small cell carcinoma of the breast is a rare breast cancer. We report two
      cases of this entity showing a non-mass-like pattern on multimodality images and
      histopathology. Both women presented with a breast mass, and one had axillary
      lymphadenopathy. Both cases revealed fine calcification on mammography (MMG) and
      an irregularly shaped, hypoechoic lesion on ultrasonography. Computed tomography
      (CT) and magnetic resonance imaging (MRI) showed non-mass-like enhancement in
      both cases. Dynamic MRI showed medium initial enhancement followed by persistent
      delayed enhancement in one patient, whereas rapid initial enhancement with
      plateau delayed enhancement was observed in the other. The breast lesions showed
      very high signal intensity on diffusion-weighted MRI. Positron emission
      tomography showed moderate accumulation of 2-fluoro-2-deoxyglucose in the breast
      tumor and lymph node metastasis. The non-mass-like enhancement on CT and MRI and
      the segmental fine calcification on MMG indicate the abundance of components of
      ductal carcinoma in situ and the breast origin of the small cell carcinoma.

PMID- 22968628
TI  - High survivin mRNA expression is a predictor of poor prognosis in breast cancer:
      a comparative study at the mRNA and protein level.
AB  - BACKGROUND: Survivin plays a key role in the initiation and progression of breast
      cancer. However, its prognostic relevance to breast cancer patients has long been
      a matter of debate. The purpose of this study was to examine the expression of
      survivin and its role in predicting clinical outcome in a series of human breast
      cancer cases both at the mRNA and protein level. METHODS: Formalin-fixed paraffin
      embedded tumor tissues from 245 female patients with invasive breast cancer and
      13 patients with ductal carcinoma in situ were examined for survivin mRNA by
      quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with
      invasive breast cancer were available for immunohistochemistry (IHC). The
      relationship between survivin status and clinicopathological characteristics and
      prognosis was evaluated. RESULTS: RT-qPCR revealed that high levels of survivin
      mRNA were strongly associated with high nuclear grade, positive axillary lymph
      nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67
      labeling index, and presence of vascular invasion. In the Cox proportional
      regression model analysis, survivin mRNA was shown to be a significant univariate
      parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS),
      and breast cancer-specific survival (BCSS) as well as a significant multivariate
      parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2
      negative subtype cases, survivin mRNA expression was also an independent
      predictor in terms of DRFS. Immunohistochemically, positive staining was seen in
      the cytoplasm and/or nucleus of cancer cells, although this did not correlate
      with the mRNA level, and harbored no prognostic value. CONCLUSIONS: High mRNA
      expression of survivin was an independent marker of poor prognosis both in the
      entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein
      expression of survivin was not. These findings suggest that RT-qPCR can provide
      more reliable data than IHC in validating the prognostic significance of survivin
      for breast cancer patients.

PMID- 22968629
TI  - Comparison of hypofractionated and conventionally fractionated whole-breast
      irradiation for early breast cancer patients: a single-institute study of 1,098
      patients.
AB  - PURPOSE: To evaluate the efficacy and safety of hypofractionated whole-breast
      irradiation (HF-WBI) compared with conventionally fractionated (CF) WBI.
      MATERIALS AND METHODS: Patients with early breast cancer (stages 0-II and <3
      positive lymph nodes) who had undergone breast-conserving surgery were eligible
      for the HF-WBI study. HF-WBI was administered at 43.2 Gy in 16 fractions over 3.2
      weeks to the whole breast with an additional tumor-bed boost of 8.1 Gy in 3
      fractions over 3 days for positive surgical margins or those <5 mm. CF-WBI was
      administered at 50 Gy in 25 fractions over 5 weeks to the whole breast with an
      additional tumor-bed boost of 16 Gy in 8 fractions over 1.4 weeks to 6 Gy in 3
      fractions over 3 days, depending on margin status. RESULTS: From April 1, 2006,
      to December 31, 2010, 717 patients were registered and 734 breasts were treated
      by HF-WBI. In the same period, 381 patients and 393 breasts who matched the study
      criteria chose CF-WBI, so the total number of patients in this comparison was
      1,098. Grade 2 acute skin reactions were observed for 24 patients (3 %) in the HF
      WBI group and 53 patients (14 %) in the CF-WBI (p < 0.001) group. The median
      follow-up period was 27 months. Two cases of intrabreast tumor recurrence were
      observed in each treatment group. Regional lymph node recurrence was observed in
      1 HF-WBI patient and 2 CF-WBI patients. CONCLUSION: HF-WBI is superior to CF-WBI
      in terms of acute skin reaction and has the same short-term efficacy.

PMID- 22968631
TI  - Controlling gas/liquid exchange using microfluidics for real-time monitoring of
      flagellar length in living Chlamydomonas at the single-cell level.
AB  - Chlamydomonas reinhardtii is widely used for studying cilia/flagella, organelles
      important for human health and disease. In situ monitoring of flagellar
      assembly/disassembly kinetics in single living cells has been difficult with
      conventional methods because of time-consuming media exchange and the requirement
      of whole cell fixation. Here, we develop a PDMS/glass hybrid microfluidic device
      for real-time tracking of flagellar length in single living cells of
      Chlamydomonas. Media exchange is precisely controlled by sequential gas-liquid
      plugs and complete medium replacement occurs within seconds. Rapid medium
      exchange allows the capture of transient flagellar dynamics. We show that
      Chlamydomonas cells respond to acidic medium exchange and deflagellate. However,
      the two flagella may shed asynchronously. After subsequent medium exchange, cells
      regenerate full-length flagella. Cells are also induced to shorten their flagella
      after being exposed to extracellular stimuli. The long-term kinetics of flagellar
      regeneration and disassembly for the whole cell population on the chip are
      comparable to those from conventional methods; however, individual cells display
      non-uniform response kinetics. We also find that flagellar growth rate is
      dependent on flagellar length. This device provides a potential platform to
      continuously monitor molecular activities associated with changes in flagellar
      length and to capture transient molecular changes upon flagellar loss, and
      initiation of flagellar assembly/disassembly.

PMID- 22968630
TI  - NYGGF4 (PID1) effects on insulin resistance are reversed by metformin in 3T3-L1
      adipocytes.
AB  - NYGGF4 (also called PID1) is a recently discovered gene that is involved in
      obesity-related insulin resistance (IR). We aimed in the present study to further
      elucidate the effects of NYGGF4 on IR and the underlying mechanisms through using
      metformin treatment in 3T3-L1 adipocytes. Our data showed that the metformin
      pretreatment strikingly enhanced insulin-stimulated glucose uptake through
      increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes.
      NYGGF4 overexpression resulted in significant inhibition of tyrosine
      phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation
      with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4
      overexpression adipocytes. The reactive oxygen species (ROS) levels in NYGGF4
      overexpression adipocytes were strikingly enhanced, which could be decreased by
      the metformin pretreatment. Our data also showed that metformin increased the
      expressions of PGC1-alpha, NRF-1, and TFAM, which were reduced in the NYGGF4
      overexpression adipocytes. These results suggest that NYGGF4 plays a role in IR
      and its effects on IR could be reversed by metformin through activating IRS
      1/PI3K/Akt and AMPK-PGC1-alpha pathways.

PMID- 22968632
TI  - Glutathione-responsive nano-transporter-mediated siRNA delivery: silencing the
      mRNA expression of Ras.
AB  - Gene therapy through antisense technology via intracellular delivery of a gene
      silencing element is a promising approach to treat critical diseases like
      cancers. Ras acts as molecular switch, considered as one of the proto-oncogenes
      whose modification or mutation may promote tumor formation. The recent trends of
      nano-carrier-based drug delivery have gained superiority and proved to be 100
      times more potent in drug delivery compared to standard therapies. The nano-based
      drug delivery has provided the basis of achieving successful target-specific drug
      delivery. Glutathione (GSH) is considered as one of the best and ubiquitous
      internal stimulus for swift destabilization of nano-transporters inside cells to
      accomplish proficient intracellular drug release. This concept has given a new
      hope to oncologists of modifying the existing drugs to be delivered to their
      desired destination. RNA interference is a primary tool in functional genomics to
      selectively silence messenger RNA (mRNA) expression, which can be exploited
      quickly to develop novel drugs against lethal disease target. Silencing of mRNA
      molecules using siRNA has also come of age to become one of the latest weapons
      developed in the concept of gene therapy. However, this strategy has severely
      failed to achieve target specificity especially to a tumor cell. In this context,
      we have proposed the incorporation of an antisense siRNA packed inside a GSH
      responsive nano-transporter to be delivered specifically to a tumor cell against
      the sense mRNA of the Ras protein. It will limit the Ras-mediated activation of
      other proteins and transcription factors. Thus, it will knock down several
      differential gene expressions being regulated by Ras-activated pathways like
      enzyme-linked receptor kinase pathway. Henceforth, gene silencing technology
      through nano-drug delivery can be combined as a single weapon to terminate
      malignancy.

PMID- 22968633
TI  - Anatomical landmarks for locating the sphenoid ostium during endoscopic endonasal
      approach: a cadaveric study.
AB  - PURPOSE: The sphenoid ostium (SO) provides a natural portal for entering the
      sphenoid sinus and beyond up to the skull base. It is not always easy to locate
      the ostium during the endoscopic approach. The present study was designed to
      establish readily identifiable anatomical landmarks for locating the sphenoid
      ostium. METHODS: Cadaveric dissection was performed in 30 hemisections of head
      and neck and various measurements were taken from fixed anatomical landmarks in
      the nasal cavity to the sphenoid ostium. The size, shape and position of sphenoid
      ostium were determined in relation to the anterior wall of the sphenoid sinus and
      the superior turbinate. RESULTS: The mean distance from the supero-lateral angle
      of the posterior choana to the SO was found to be 21.21 +/- 6.02 mm. The mean
      distance of the SO from the midline was 4.85 +/- 2.89 mm. In all the specimens,
      the SO was situated within 1 cm of the midline. The mean distance between the
      inferior end of the SO and the postero-inferior edge of the superior turbinate
      was 8.03 +/- 3.52 mm. The SO was present on an average distance of 55.1 +/- 3.54
      mm from the limen nasi. In 93.3 % of the specimens, the SO was situated between 5
      and 6 cm of the inferior end of the limen nasi. The angle between the anterior
      nasal spine and the SO was found to be remarkably constant. In 93.3 % of the
      specimens, it was from 25 degrees  to 30 degrees . CONCLUSIONS: The sphenoid
      ostium could be localized medial to the superior turbinate between 1.5 and 3 cm
      above the supero-lateral angle of the posterior choana, within 1 cm of the
      midline and within 1 cm of the postero-inferior edge of the superior turbinate.

PMID- 22968634
TI  - Ring formation of the internal iliac artery.
AB  - We observed an arterial ring communicating the superior and inferior gluteal
      arteries in the left half of the pelvis of an 88-year-old male. Although many
      previous studies have shown variations in the internal iliac artery, there has
      been no literature describing the fenestration. Therapeutic embolization is
      commonly performed for intractable bleeding in pelvic region. Surgeons should be
      aware of the arterial ring formation because of possible danger in the
      intravascular treatments. In patients with similar arterial rings, embolization
      of the anterior trunk of the internal iliac artery could be insufficient when
      blood runs through the circle of the arterial ring.

PMID- 22968636
TI  - Ortho-substituent induced triradical-containing tetranuclear oxo-vanadium(IV)
      cluster formation via ligand C-N bond breaking and C-O bond making.
AB  - Substituent having weak-coordination character, and attached at the ortho-carbon
      atom to the aniline moiety of 2-anilino-4,6-di-tert-butylphenol, provided a
      triradical-containing tetranuclear vanadium(IV) complex via ligand C-N bond
      breaking and C-O bond making.

PMID- 22968637
TI  - Microarray and proteomic analysis of the cardioprotective effects of cold blood
      cardioplegia in the mature and aged male and female.
AB  - Recently we have shown that the cardioprotection afforded by cardioplegia is
      modulated by age and gender and is significantly decreased in the aged female. In
      this report we use microarray and proteomic analyses to identify transcriptomic
      and proteomic alterations affecting cardioprotection using cold blood
      cardioplegia in the mature and aged male and female heart. Mature and aged male
      and female New Zealand White rabbits were used for in situ blood perfused
      cardiopulmonary bypass. Control hearts received 30 min sham ischemia and 120 min
      sham reperfusion. Global ischemia (GI) hearts received 30 min of GI achieved by
      cross-clamping of the aorta. Cardioplegia (CP) hearts received cold blood
      cardioplegia prior to GI. Following 30 min of GI the hearts were reperfused for
      120 min and then used for RNA and protein isolation. Microarray and proteomic
      analyses were performed. Functional enrichment analysis showed that mitochondrial
      dysfunction, oxidative phosphorylation and calcium signaling pathways were
      significantly enriched in all experimental groups. Glycolysis/gluconeogenesis and
      the pentose phosphate pathway were significantly changed in the aged male only (P
      < 0.05), while glyoxylate/dicarboxylate metabolism was significant in the aged
      female only (P < 0.05). Our data show that specific pathways associated with the
      mitochondrion modulate cardioprotection with CP in the aged and specifically in
      the aged female. The alteration of these pathways significantly contributes to
      decreased myocardial functional recovery and myonecrosis following ischemia and
      may be modulated to allow for enhanced cardioprotection in the aged and
      specifically in the aged female.

PMID- 22968638
TI  - MiR-351 transiently increases during muscle regeneration and promotes progenitor
      cell proliferation and survival upon differentiation.
AB  - MicroRNAs (miRNAs) regulate many biological processes including muscle
      development. However, little is known regarding miRNA regulation of muscle
      regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin
      induced injury and used for global miRNA expression analysis. From day 1 through
      day 21 following injury, 298 miRNAs were significantly changed at least at one
      time point, including 86 miRNAs that were altered >10-fold compared with
      uninjured skeletal muscle. Temporal miRNA expression patterns included
      inflammation-related miRNAs (miR-223 and -147) that increased immediately after
      injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, 
      133a, and -499) that abruptly decreased following injury followed by upregulation
      in later regenerative events. Another cluster of miRNAs were transiently
      increased in the early days of muscle regeneration including miR-351, a miRNA
      that was also transiently expressed during myogenic progenitor cell (MPC)
      differentiation in vitro. Based on computational predictions, further studies
      demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown
      of miR-351 expression inhibited MPC proliferation and promoted apoptosis during
      MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis
      during differentiation. Collectively, these observations suggest that miR-351 is
      involved in both the maintenance of MPC proliferation and the transition into
      differentiated myotubes. Thus, a novel, time-dependent sequence of molecular
      events during muscle regeneration has been identified; miR-351 inhibits E2f3
      expression, a key regulator of cell cycle progression and proliferation, and
      promotes MPC proliferation and protects early differentiating MPC from apoptosis,
      important events in the hostile tissue environment after acute muscle injury.

PMID- 22968639
TI  - Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits.
AB  - Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] * ZUC-Lepr (faSte)
      (ZUC)} * ZUC identified a male-specific quantitative trait locus (QTL) for
      urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42
      D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb
      from chromosome 1 on the ZUC background. We observed threefold higher urinary
      albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males
      than in same sex and age congenic animals when both strains are also homozygous
      for the ZUC leptin receptor fatty mutation (Lepr (faSte)) (P < 0.0001). We then
      linkage mapped within the donor region without confounded effects from other
      chromosomes. Phenotypes were collected in 248 F2 male rats in a population made
      by crossing parents heterozygous for both the BN donor region and ZUC Lepr
      (faSte). Significant interactions were observed between the Lepr genotype and
      chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR,
      right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR,
      exhibit a second peak at the distal end of the chromosome. Hydronephrosis
      exhibited one or two QTLs contingent on adjustment for body weight. The results
      now demonstrate at least two sets of coincident traits with different
      correlations to kidney function.

PMID- 22968640
TI  - Neural hijacking: action of high-frequency electrical stimulation on cortical
      circuits.
AB  - Electrical stimulation of the brain was one of the first experimental methods
      applied to understanding brain organization and function and it continues as a
      highly useful method both in research and clinical applications. Intracortical
      microstimulation (ICMS) involves applying electrical stimuli through a
      microelectrode suitable for recording the action potentials of single neurons.
      ICMS can be categorized into single-pulse stimulation; high-frequency, short
      duration stimulation; and high-frequency, long-duration stimulation. For clinical
      and experimental reasons, considerable interest focuses on the mechanism of
      neural activation by electrical stimuli. In this article, we discuss recent
      results suggesting that action potentials evoked in cortical neurons by high
      frequency electrical stimulation do not sum with the natural, behaviorally
      related background activity; rather, high-frequency stimulation eliminates and
      replaces natural activity. We refer to this as neural hijacking. We propose that
      a major component of the mechanism underlying neural hijacking is excitation of
      axons by ICMS and elimination of natural spikes by antidromic collision with
      stimulus-driven spikes evoked at high frequency. Evidence also supports neural
      hijacking as an important mechanism underlying the action of deep brain
      stimulation in the subthalamic nucleus and its therapeutic effect in treating
      Parkinson's disease. 

PMID- 22968641
TI  - Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic
      Barrett's esophagus.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) of early
      gastrointestinal tumors has been shown to achieve complete resection rates
      superior to endoscopic mucosal resection (EMR), but at the cost of higher risk.
      The aim of this study was to prospectively assess the feasibility and oncological
      results of ESD in patients with neoplastic Barrett's esophagus in conjunction
      with subsequent radiofrequency ablation (RFA). METHODS: Patients with Barrett's
      esophagus who had visible lesions containing high grade intraepithelial neoplasia
      (HGIN) or mucosal adenocarcinoma (MAC) up to 3 cm in diameter were included in
      the study. ESD was performed using a new waterjet-assisted system (WESD) with a
      HybridKnife (Erbe Elektromedizin GmbH, Tubingen, Germany). Primary outcome was
      the rate of complete tumor resection. RFA of residual intestinal metaplasia was
      offered to all patients with at least two negative follow-up endoscopies.
      RESULTS: Of 30 patients (m:f = 21:9; median age 60 years) with biopsy-proven MAC
      (n = 24) or HGIN (n = 6) with a median diameter of 2 cm, complete resection of
      the targeted area was achieved in 29 patients (96.7 %; 95 % confidence interval
      [CI] 82 % - 99 %); en bloc resection was achieved in 27 of these patients (90.0
      %; 95 %CI 74 % - 97 %). Minor delayed bleedings occurred in two patients. One
      patient died due to a sudden cardiac death 7 days after an uneventful WESD.
      Specimen histology (n = 29) revealed no neoplasia in 3 patients, HGIN in 2, MAC
      in 21, and submucosal cancer in 3; complete resection was histologically
      confirmed in only 10 of the 26 patients with HGIN or adenocarcinoma (38.5 %; 95
      %CI 22 % - 57 %). However, endoscopic follow-up (median 17 months) showed
      complete remission of neoplasia in 27 /28 (96.4 %; 95 %CI 81 % - 99 %) patients
      who underwent successful WESD and were alive at 30 days. One patient underwent
      EMR of residual tumor. All Barrett's tissue was eradicated by ESD alone in 15
      cases and by additional RFA in 8 /10 cases (not done in three patients).
      CONCLUSIONS: ESD of Barrett's neoplasia is feasible and safe, but does not
      achieve sufficient R0 resection rates to warrant its recommended use over
      piecemeal EMR. In combination with RFA it can achieve complete eradication of
      neoplastic and non-neoplastic Barrett's epithelium. The discrepancy between
      insufficient oncological resection and good medium-term results needs to be
      studied further.

PMID- 22968642
TI  - Migration of cells from experimental endometriosis to the uterine endometrium.
AB  - Endometriosis is the estrogen-dependent growth of endometrial tissue outside the
      uterus. Endometriosis has an effect on the eutopic endometrium; however, the
      nature of the cellular or molecular signal from the lesion to the uterus is
      unknown. Here we demonstrate that cells migrate from endometriosis to eutopic
      endometrium. Experimental endometriosis was established by transplanting
      endometrial tissue from green fluorescent protein (GFP) mice to the peritoneal
      cavity of DS-Red mice. Immunofluorescence (IF) identified cells from the ectopic
      lesions in the uterus. The eutopic endometrial cells were sorted by fluorescence
      activated cell sorting, and the GFP(+)/DS-Red(-) population was characterized
      using microarray analysis. The results of cell sorting as well as the array
      results were confirmed by quantitative PCR and IF. GFP(+)/DS-red(-)/Cd45(-) cells
      were identified in the eutopic endometrium of mice with experimental endometriois
      (~1.8%) and not in controls. Global gene expression profiling of these cells
      showed absence of leukocyte and increased expression of pan-epithelial markers in
      the uterine GFP(+) cells. Moreover, GFP(+) cells showed up-regulation of Wnt7A
      expression and 17 other genes associated with the Wingless pathway. Several genes
      that are associated with epithelial-to-mesenchymal transition were also highly
      differentially expressed in GFP(+) cells. IF confirmed the presence of the
      GFP(+)/CD45(-)/Wnt7a(+)/cytokeritin(+) cells in the endometrium of endometriotic
      animals, and not in controls. Cells from endometriotic lesions are capable of
      migrating to the eutopic endometrium. The ectopic expression of Wnt7A suggests a
      possible mechanism by which ectopic lesions affect the eutopic endometrium and
      interfere with embryo implantation and fertility.

PMID- 22968643
TI  - Thyroid hormone signaling in the Xenopus laevis embryo is functional and
      susceptible to endocrine disruption.
AB  - Thyroid hormone (TH) is essential for vertebrate brain development. Most research
      on TH and neuronal development focuses on late development, mainly the perinatal
      period in mammals. However, in human infants neuromotor development correlates
      best with maternal TH levels in the first trimester of pregnancy, suggesting that
      TH signaling could affect early brain development. Studying TH signaling in early
      embryogenesis in mammals is experimentally challenging. In contrast, free-living
      embryos, such as Xenopus laevis, permit physiological experimentation independent
      of maternal factors. We detailed key elements of TH signaling: ligands, receptors
      (TR), and deiodinases during early X. laevis development, before embryonic
      thyroid gland formation. Dynamic profiles for all components were found. Between
      developmental stages 37 and 41 (~48 h after hatching, coincident with a phase of
      continuing neurogenesis) significant increases in T(3) levels as well as in mRNA
      encoding deiodinases and TR occurred. Exposure of embryos at this developmental
      stage for 24 h to either a TH antagonist, NH-3, or to tetrabromobisphenol A, a
      flame retardant and known TH disruptor, differentially modulated the expression
      of a number of TH target genes implicated in neural stem cell function or neural
      differentiation. Moreover, 24-h exposure to either NH-3 or tetrabromobisphenol A
      diminished cell proliferation in the brain. Thus, these data show first, that TH
      signaling exerts regulatory roles in early X. laevis neurogenesis and second,
      that this period represents a potential window for endocrine disruption.

PMID- 22968644
TI  - Palmitate causes endoplasmic reticulum stress and apoptosis in human mesenchymal
      stem cells: prevention by AMPK activator.
AB  - Elevated circulating saturated fatty acids concentration is commonly associated
      with poorly controlled diabetes. The highly prevalent free fatty acid palmitate
      could induce apoptosis in various cell types, but little is known about its
      effects on human mesenchymal stem cells (MSCs). Here, we report that prolonged
      exposure to palmitate induces human bone marrow-derived MSC (hBM-MSC) and human
      umbilical cord-derived MSC apoptosis. We investigated the role of endoplasmic
      reticulum (ER) stress, which is known to promote cell apoptosis. Palmitate
      activated XBP1 splicing, elF2alpha (eukaryotic translation initiation factor
      2alpha) phosphorylation, and CHOP, ATF4, BiP, and GRP94 transcription in hBM
      MSCs. ERK1/2 and p38 MAPK phosphorylation were also induced by palmitate in hBM
      MSCs. A selective p38 inhibitor inhibited palmitate activation of the ER stress,
      whereas the ERK1/2 inhibitors had no effect. The AMP-activated protein kinase
      activator aminoimidazole carboxamide ribonucleotide blocked palmitate-induced ER
      stress and apoptosis. These findings suggest that palmitate induces ER stress and
      ERK1/2 and p38 activation in hBM-MSCs, and AMP-activated protein kinase activator
      prevents the deleterious effects of palmitate by inhibiting ER stress and
      apoptosis.

PMID- 22968645
TI  - Beyond synergy: corticosterone and thyroid hormone have numerous interaction
      effects on gene regulation in Xenopus tropicalis tadpoles.
AB  - Hormones play critical roles in vertebrate development, and frog metamorphosis
      has been an excellent model system to study the developmental roles of thyroid
      hormone (TH) and glucocorticoids. Whereas TH regulates the initiation and rate of
      metamorphosis, the actions of corticosterone (CORT; the main glucocorticoid in
      frogs) are more complex. In the absence of TH during premetamorphosis, CORT
      inhibits development, but in the presence of TH during metamorphosis, CORT
      synergizes with TH to accelerate development. Synergy at the level of gene
      expression is known for three genes in frogs, but the nature and extent of TH and
      CORT cross talk is otherwise unknown. Therefore, to examine TH and CORT
      interactions, we performed microarray analysis on tails from Xenopus tropicalis
      tadpoles treated with CORT, TH, CORT+TH, or vehicle for 18 h. The expression of
      5432 genes was significantly altered in response to either or both hormones.
      Using Venn diagrams and cluster analysis, we identified 16 main patterns of gene
      regulation due to up- or down-regulation by TH and/or CORT. Many genes were
      affected by only one of the hormones, and a large proportion of regulated genes
      (22%) required both hormones. We also identified patterns of additive or
      synergistic, inhibitory, subtractive, and annihilatory regulation. A total of 928
      genes (17%) were regulated by novel interactions between the two hormones. These
      data expand our understanding of the hormonal cross talk underlying the gene
      regulation cascade directing tail resorption and suggest the possibility that
      CORT affects not only the timing but also the nature of TH-dependent tissue
      transformation.

PMID- 22968646
TI  - Aripiprazole differentially regulates the expression of Gad67 and gamma
      aminobutyric acid transporters in rat brain.
AB  - The molecular etiology of schizophrenia comprises abnormal neurotransmission of
      the amino acid GABA (gamma-aminobutyric acid). Neuropathological studies
      convincingly revealed reduced expression of glutamic acid decarboxylase (Gad67)
      in GABAergic interneurons. Several antipsychotics influence the expression of
      GABAergic genes, but aripiprazole (APZ), a partial dopaminergic and serotonergic
      receptor agonist, has not been involved into these studies so far. We treated
      Sprague-Dawley rats for 4 weeks or 4 months with APZ suspended in drinking water
      and doses of 10 and 40 mg per kg body weight. Gene expression of Gad67, the
      vesicular GABA transporter Slc32a1 (solute carrier family, Vgat), the
      transmembrane transporters Slc6a1 (Gat1) and Slc6a11 (Gat3) was assessed by
      semiquantitative radioactive in situ hybridization. APZ treatment resulted in
      time- and dose-dependent effects with qualitative differences between brain
      regions. In the 10-mg group, Slc6a1 was strongly induced after 4 weeks in the
      hippocampus, amygdala, and cerebral cortex, followed by an induction of Gad67 in
      the same regions after 4 months, while frontocortical regions as well as basal
      ganglia showed dose-dependent reductions of Gad67 expression after 4 months. In
      several frontocortical and subcortical regions, we observed a decrease of Slc32a1
      and an increase of Slc6a11 expression. In conclusion, APZ modulates gene
      expression of GABAergic marker genes involved into pathogenetic theories of
      schizophrenia. APZ only partially mirrors the effects of other antipsychotics
      with some important differences regarding brain regions. The findings might be
      explained by regulatory connections between serotonergic, GABAergic, and
      dopaminergic neurotransmission and should be validated in behavioral animal
      models of psychotic disorders.

PMID- 22968647
TI  - Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal
      carcinoma: a case-control study in Italy.
AB  - BACKGROUND: Dietary habits have been related to the risk of nasopharyngeal
      carcinoma (NPC), but information on a wide range of macro- and micronutrients is
      still lacking, particularly for low-incidence countries. METHODS: We conducted a
      hospital-based case-control study in Italy on 198, histologically confirmed, NPC
      cases of Caucasian ethnicity of 18-76 years of age. Controls were 594 Caucasian
      cancer-free patients admitted to general hospitals for acute conditions.
      Nutrients intake was assessed through a validated food-frequency questionnaire.
      Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were
      estimated through logistic regression. RESULTS: Dietary intake of carotenoids
      were inversely related to NPC risk, notably carotene (OR for highest vs lowest
      quartile=0.46; 95% CI: 0.26-0.79), alpha-carotene (OR=0.57; 95% CI: 0.33-0.97),
      and beta-carotene (OR=0.42; 95% CI: 0.24-0.75). Increased NPC risk was observed
      for elevate cholesterol intake (OR=1.85; 95% CI: 1.12-3.05). CONCLUSION: Study
      findings suggest a protective effect of carotenoids against NPC in a low-risk
      population, adding further support to a possible beneficial role of a diet rich
      in fruits and vegetables in cancers of the head and neck.

PMID- 22968648
TI  - Diagnosis of bladder cancer by immunocytochemical detection of minichromosome
      maintenance protein-2 in cells retrieved from urine.
AB  - BACKGROUND: We tested the accuracy of immunocytochemistry (ICC) for
      minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using
      cells retrieved from urine. METHODS: Adequate samples were obtained from 497
      patients, the majority presenting with gross haematuria (GH) or undergoing
      cystoscopic surveillance (CS) following previous bladder cancer. We performed an
      initial study of 313 patients, followed by a validation study of 184 patients. In
      all cases, presence/absence of bladder cancer was established by
      cystoscopy/biopsy. RESULTS: In the initial study, receiver operator
      characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for
      the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity
      were provided by threshold values of 50+ MCM-2-positive cells in GH samples and
      200+ cells in CS samples, based on a minimum total cell number of 5000. Applying
      these thresholds to the validation data set gave 81.3% sensitivity, 76.0%
      specificity and 92.7% negative predictive value (NPV) in GH and 63.2%
      sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance
      protein-2 ICC provided clinically relevant improvements over urine cytology, with
      greater sensitivity in GH and greater specificity in CS (P=0.05). CONCLUSIONS:
      Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that
      is suitable for both GH and CS patient groups.

PMID- 22968650
TI  - Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences
      between high-incidence and low-incidence areas.
AB  - BACKGROUND: There is a need for sensitive and specific blood-borne markers for
      the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF)
      levels have been proposed as a marker for gastric cancer diagnosis but, to date,
      studies have only encompassed patients from high-incidence areas. METHODS: We
      have compared the serum concentration of MIF in a large cohort of UK and Japanese
      gastric cancer patients, together with appropriate control subjects (age and
      gender matched). Carcinoembryonic antigen and H. pylori IgG were also measured,
      as was DJ-1, a novel candidate protein biomarker identified by analysis of
      gastric cancer cell line secretomes. RESULTS: Marked elevations of the serum
      concentration of MIF and DJ-1 were seen in Japanese patients with gastric cancer
      compared with Japanese controls, a trend not seen in the UK cohort. These results
      could not be accounted for by differences in age, disease stage or H. pylori
      status. CONCLUSION: In regions of high, but not low incidence of gastric cancer,
      both MIF and DJ-1 have elevated serum concentrations in gastric cancer patients,
      compared with controls. This suggests that differing mechanisms of disease
      pathogenesis may be at play in high- and low-incidence regions.

PMID- 22968649
TI  - Case-control study of paternal occupation and childhood leukaemia in Great
      Britain, 1962-2006.
AB  - BACKGROUND: Paternal occupational exposures have been proposed as a risk factor
      for childhood leukaemia. This study investigates possible associations between
      paternal occupational exposure and childhood leukaemia in Great Britain. METHODS:
      The National Registry of Childhood Tumours provided all cases of childhood
      leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls
      were matched on sex, period of birth and birth registration subdistrict. Fathers'
      occupations were assigned to 1 or more of 33 exposure groups. Social class was
      derived from father's occupation at the time of the child's birth. RESULTS: A
      total of 16 764 cases of childhood leukaemia were ascertained. One exposure
      group, paternal social contact, was associated with total childhood leukaemia
      (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted
      for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid
      leukaemia showed increased risk with paternal exposure to social contact before
      adjustment for social class. Risk of other leukaemias was significantly increased
      by exposure to electromagnetic fields, persisting after adjustment for social
      class. For total leukaemia, the risks for exposure to lead and exhaust fumes were
      significantly <1. Occupationally derived social class was associated with risk of
      LL, with the risk being increased in the higher social classes. CONCLUSION: Our
      results showed some support for a positive association between childhood
      leukaemia risk and paternal occupation involving social contact. Additionally, LL
      risk increased with higher paternal occupational social class.

PMID- 22968651
TI  - Prognostic factors for survival in patients with metastatic renal cell carcinoma
      treated with targeted therapies.
AB  - BACKGROUND: The most important prognostic factors for survival in patients with
      metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine
      therapy, and only recently were revalidating in patients receiving targeted
      therapies (TTs). METHODS: Clinical data for consecutive patients with mRCC who
      received TTs were retrieved from the database of Istituto Nazionale dei Tumori of
      Milan. Variables with a significant association with overall survival (OS) were
      estimated by proportional hazard regression, and a backward stepwise multivariate
      analysis identified the independent prognostic factors. RESULTS: Data for 336
      consecutive patients treated with TTs for RCC during the period 2004-2011 were
      evaluated. According to the Motzer classification, 32% patients were low risk,
      48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven
      (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42
      (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The
      median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95%
      CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk
      classification, Fuhrman grade and previous cytokine therapy were identified as
      independent prognostic factors (P<0.01). CONCLUSION: The Motzer classification
      was confirmed as an independent prognostic factor for OS in patients with mRCC
      receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were
      independent prognostic factors for clinical outcome.

PMID- 22968652
TI  - Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory
      cancer patients: impact on short-term survival.
AB  - BACKGROUND: Asymptomatic venous thrombotic events (VTEs) are possible findings in
      ambulatory cancer patients. Data regarding the incidence and clinical impact of
      asymptomatic VTEs are conflicting. We therefore conducted a study to evaluate the
      occurrence of asymptomatic VTEs of the lower limbs in ambulatory cancer patients
      to further evaluate the association of these asymptomatic VTEs on survival during
      a 9-month follow-up period. METHODS: In our prospective cohort, we included 150
      consecutive ambulatory cancer patients who were free of any clinical symptoms for
      VTEs. Compression ultrasound to detect deep vein thrombosis (DVT) and superficial
      venous thrombosis (SVT) of the lower limbs was performed by a vascular specialist
      in all patients at baseline. In case of pathological findings the patients were
      treated with low molecular weight heparin (LMWH) because of current established
      guidelines. The occurrence of death was investigated during a 9-month follow-up
      period. RESULTS: A total of 27 (18%) patients with VTEs were detected, which
      included 13 patients (8.7%) with a SVT and 16 patients (10.7%) showing a DVT. Two
      patients had both, a SVT and a DVT as well. During the 9-month follow-up period
      the occurrence of a VTE at baseline was associated with a 2.4-fold increased risk
      for death (HR 2.4 (1.2-5.3); P=0.03). CONCLUSION: Asymptomatic VTEs of the lower
      limbs in ambulatory cancer patients are frequently occurring concomitant features
      and are associated with poor survival during a 9-month follow-up period despite
      anticoagulation with LMWH.

PMID- 22968653
TI  - Precise, fast, and flexible determination of protein interactions by affinity
      capillary electrophoresis: part 1: performance.
AB  - A generic screening approach was performed to investigate the binding of various
      potential ligands to proteins in order to investigate how proteins interact with
      ions and the complete surrounding solution. This also allows to study binding
      behavior and its regulation and protein functionality in general in a native
      environment. The ACE technique affords an excellent precision by applying
      appropriate rinsing procedures using a pressure of 2.5 bar and a continuous flow
      concept. Confidence intervals were estimated to proof significance of the
      interactions. This enables to investigate smaller yet important interactions,
      which were not possible with less precise techniques before. The influence of
      various ions on ovalbumin, beta-lactoglobulin, and BSA were screened by comparing
      the mobility ratios of the free protein and the influenced one. The analysis was
      performed using the metal ions Ba(2) +, Ca(2) +, Cu(2) +, Mg(2) +, Mn(2) +, Ni(2)
      +, the pharmaceutical cations ephedrine hydrochloride, ethambutol
      dihydrochloride, pilocarpine hydrochloride and pirenzepine dihydrochloride, and
      various anions, in particular phosphate, acetate, succinate, glutamate, and
      salicylate. For the anion influence study, myoglobin was also included to the
      screened proteins. The influence of these ions on the proteins was well
      diversified. The interactions could be distinguished with a fast and precise
      screening method since 90% of all mobility ratios had a RSD% below 2% and 79% had
      a RSD% lower than 1%. Hence, for more than 75% of the protein-ligand pairs
      significant interactions are observed with a very small confidence interval due
      to the very excellent precision of these used method.

PMID- 22968654
TI  - Ytterbium can relax slowly too: a field-induced Yb2 single-molecule magnet.
AB  - An unusual dinuclear Yb(2) complex isolated using a mixed ligand strategy leads
      to field-induced SMM behaviour. Low magnetic axiality and a large tunnelling gap
      lead to significant quantum tunnelling of the magnetisation, which was reduced
      under an applied static optimum field of 1600 Oe.

PMID- 22968655
TI  - Influence of substituent effects on spectroscopic properties and antimicrobial
      activity of 5-(4'-substituted phenylazo)-2-thioxothiazolidinone derivatives.
AB  - 5-(4'-substituted phenylazo)-2-thioxothiazolidinone derivatives (HL(n)) have been
      synthesized and characterized by elemental analysis, spectra (IR, electronic and
      (1)H NMR). The IR spectral data indicate that the compounds can exist in two
      resonance structures. The synthesized ligands were screened for their
      antimicrobial activity against four bacterial species, two Gram positive bacteria
      (Bacillus cereus and Staphylococcus aureus) and two Gram negative bacteria
      (Escherichia coli and Klebsiella pneumoniae) as well as against some species
      various of fungi; Aspergillus niger, Penicillium chrysogenum, Penicillium
      italicum and Fusarium oxysporium. The results showed that most these ligands are
      good antibacterial agents against B. cereus and S. aureus and antifungal agents
      against A. niger and F. oxysporium. HL(3) was found to be the most effect
      compound against all tested microorganisms. The size of clear zone were ordered
      as follows p-(OCH(3) < CH(3) < H < Cl < NO(2)) as expected from Hammett's
      constant sigma(R).

PMID- 22968656
TI  - Brain metastases after breast-conserving therapy and systemic therapy: incidence
      and characteristics by biologic subtype.
AB  - The characteristics of brain metastases (BM) that develop after breast-conserving
      therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We
      examined 1,434 consecutive patients with stage I/II invasive BC who received BCT
      from 1997 to 2006, 91 % of whom received adjuvant systemic therapy, according to
      BC subtype. Median follow-up was 85 months. Overall 5-year cumulative incidence
      of BM was 1.7 %; 0.1 % for luminal A, 3.3 % for luminal B, 3.2 % for luminal
      HER2, 3.7 % for HER2, and 7.4 % for triple negative (TN). Women who developed BM
      were more likely at BC diagnosis to be younger (P < .0001) and have node-positive
      (P < .0001), grade 3 (P < .0001), hormone receptor-negative (P = .006), and HER2
      positive (P = .01) tumors. Median time from BC diagnosis to BM was 51.4 months
      (range, 7.6-108 months), which was longer among luminal versus non-luminal
      subtypes (P = .0002; median, 61.4 vs. 34.5 months). Thirty-four percent of
      patients who developed distant metastases (DM) eventually developed BM. Median
      time from DM to BM was 12.8 months but varied by subtype, including 7.4 months
      for TN, 9.6 months for luminal B, and 27.1 months for HER2. Eighty-one percent of
      all BM patients presented with neurologic symptoms. Median number of BM at
      diagnosis was two, and median BM size was 15 mm, with TN (27 mm) and luminal B
      (16 mm) exhibiting the largest median sizes. In conclusion, the risk of BM after
      BCT varies significantly by subtype. Given the large size and symptomatic
      presentation among luminal B and TN subtypes, earlier BM detection might improve
      quality of life or increase eligibility for non-invasive treatments including
      stereotactic radiosurgery. Women with DM from these two BC subtypes have a high
      incidence of BM with a short latency, suggesting an ideal target population for
      trials evaluating the utility of MRI screening.

PMID- 22968657
TI  - Photochemical and thermal spiropyran (SP)-merocyanine (MC) interconversion: a
      dichotomy in dependence on viscosity.
AB  - The current study extends our work with spiropyran-merocyanines (SP-MC) as
      molecular photoswitches by delving into the effects of viscosity. This has led to
      the interesting finding of a dichotomy in viscosity dependence. Solutions of SP
      [6'-nitro-1,3,3-trimethylspiro(indolino-2,2'-benzopyran)] in a wide range of
      ethylene glycol-methanol (EG-MeOH) media (3.59 to 17.9 M in EG) were irradiated
      90 s (365 nm). The absorbance at 90 s of MC (532 nm) formed photolytically varied
      with solvent. The least viscous medium yielded the highest concentration of MC
      and yields declined with increasing viscosity. Once irradiation ceased each
      system achieved thermal equilibrium. Molecular dynamics studies of typical
      thermal reactions governed by electronic and steric factors show that the
      transition state is achieved primarily after solvent reorganization has occurred
      to accommodate the new structure. It follows that in such thermal reactions
      viscosity may not cause any hindrance to the motion of atoms in molecules because
      solvent has already rearranged. In contrast, photochemical excitations occur at
      much higher rates (10(-15) s) than solvent reorganization, i.e. dielectric
      relaxation (10(-10) to 10(-12) s). The viscosity dependence of photochemical MC
      formation suggests that a major geometrical change is required for excited SP to
      be converted to MC. The dichotomy in dependence on viscosity is confirmed by the
      thermal equilibration of SP and MC. The equilibrium constant for the process
      increases three-fold (from 0.0535 to 0.158) as the EG content of the medium
      increases. However, the forward rate constant (SP -> MC) is almost invariant with
      EG content or viscosity. The process is viscosity independent. The increase in
      the equilibrium constant with EG concentration is a result of a decline in the
      reverse rate constant for MC cyclisation to SP. This is attributed to special
      stabilisation of the MC that increases with increasing EG concentration. The
      present study, to our knowledge, is the first to dissect viscosity from solvent
      stabilisation factors in SP-MC systems. Further, the study highlights the
      fundamental difference between photolytic and thermal processes, providing
      another avenue of control for these SP-MC photoswitches.

PMID- 22968658
TI  - Leptin stimulation of cell cycle and inhibition of apoptosis gene and protein
      expression in OVCAR-3 ovarian cancer cells.
AB  - The OVCAR-3 cell line expressing the long (ObRb) and short (ObRt) isoforms of
      leptin receptor mRNA was used to analyze the effect of leptin on the expression
      of selected genes and proteins involved in the cell cycle and apoptosis. OVCAR-3
      cells were exposed to 2, 20, 40, and 100 ng/ml of leptin. Cell proliferation was
      determined using the alamarBlue cell viability test and flow cytometry. Apoptosis
      was measured using a cellular DNA fragmentation ELISA kit. The expression of
      selected cell cycle and apoptosis genes was evaluated by real-time PCR and
      confirmed by western blot. The stimulatory action of leptin on cell proliferation
      was observed as an increase in cells in the S and G2/M phases. Up-regulation of
      genes responsible for inducing cell proliferation and suppression of genes
      responsible for inhibition of proliferation were noted. Western blots revealed
      increased expression of cyclins D and A and inhibition of p21WAF1/CIP1 protein
      expression by leptin. Inhibition of DNA fragmentation was observed under all
      leptin doses. Suppression of genes involved in the extrinsic and intrinsic
      apoptotic pathway was observed. Western blots illustrated decreased Bad, TNFR1,
      and caspase 6 protein expression in response to leptin treatment. Leptin promotes
      ovarian cancer cell line growth by up-regulating genes and proteins responsible
      for inducing cell proliferation as well as down-regulating pro-apoptotic genes
      and proteins in apoptotic pathways. Results of this study warrant examining the
      relationship between the risk of ovarian cancer and elevated leptin levels in
      obese women.

PMID- 22968660
TI  - Notch1 signaling is irresponsible to the anti-leukemic effect of HDACis in B-ALL
      Nalm-6 cells.
AB  - B cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematologic
      malignancy with limited treatment strategies. Histone deacetylases inhibitors
      (HDACis) are promising novel tools for cancer therapy, whose anti-tumor effects
      and the underlying mechanisms on B-ALL remain to be elucidated. Recently, Notch1
      signaling activation has been reported to be involved in the anti-tumor effects
      of HDACis. This study was conducted to determine: the influence of two HDACis,
      valproic acid (VPA) and suberic bishydroxamic acid (SBHA), on Notch1 signaling as
      well as the role of Notch1 signaling in the anti-tumor effects of HDACis in B-ALL
      cells. To address this issue, we treated Nalm-6 B-ALL cell line with VPA and SBHA
      (HDACis), then, cell proliferation, cell cycle, apoptosis, and expression of
      Notch1 related genes were analyzed. We found that VPA and SBHA dramatically
      inhibited cell growth, induced a G1/S cell cycle block in accompany with an
      elevated level of P21(WAF1) protein in Nalm-6 cells. The levels of cleaved
      caspase-9, caspase-3, and PARP were elevated, indicating the activation of
      apoptosis. However, no change in the expression of Notch1 and its downstream
      genes were found by quantitative real-time PCR and Western blot. Our result
      suggested that Notch1 signaling is irresponsible for the anti-leukemic effect of
      HDACis in B-ALL cells. New hypotheses and future studies are needed to explore
      the underlying mechanisms of the anti-cancer effect in B-ALL.

PMID- 22968659
TI  - Simultaneous blockade of dopamine and noradrenaline reuptake promotes
      disadvantageous decision making in a rat gambling task.
AB  - RATIONALE: The inability to make profitable long-term decisions has been
      implicated in several psychiatric disorders. There is emerging evidence to
      support a role for dopamine (DA) in decision making, but our understanding of the
      role of noradrenaline (NA) and serotonin (5-HT) in decision making, and of
      possible interactions between the three monoamines, is limited. Moreover,
      impulsivity has been associated with aberrant decision making, but the underlying
      mechanisms are incompletely understood. OBJECTIVE: The purpose of this study is
      to improve our understanding of the neuropharmacological mechanisms of decision
      making and impulse control. METHODS: We investigated the effects of amphetamine
      (0.25-1.0 mg/kg) and selective reuptake inhibitors of DA (GBR12909; 2.5-10
      mg/kg), NA (atomoxetine; 0.3-3.0 mg/kg), and 5-HT (citalopram; 0.3-3.0 mg/kg) in
      a rat gambling task (rGT). Since the rGT allows for detection of impulsive
      action, i.e., premature responding, we also assessed the relationship between
      decision making and impulsivity. RESULTS: In the rGT, rats developed an optimal
      choice strategy from the first session onwards. Elevation of endogenous DA or NA
      levels increased and decreased impulsivity, respectively, but did not alter
      decision making. However, simultaneous blockade of DA and NA disrupted decision
      making, reflected by a relative decrease in choice for the advantageous choice
      options. Increasing 5-HT neurotransmission did not affect decision making or
      impulsivity. CONCLUSIONS: These data suggest important but complementary or
      redundant roles of DA and NA neurotransmission in decision-making processes based
      on reward probability and punishment. Moreover, impulse control and decision
      making in the rGT rely on dissociable mechanisms.

PMID- 22968661
TI  - Body mass index and bioelectrical impedance phase angle as potentially modifiable
      nutritional markers are independent risk factors for outcome in allogeneic
      hematopoietic cell transplantation.
AB  - Beside many risk factors in patients considered for alloHCT, only body mass index
      (BMI) as a broad marker of nutritional status has prognostic value in these
      patients. This is the first prospective study to investigate the validity of
      further nutritional markers: adjusted BMI, normalized for gender and age;
      Subjective Global Assessment questionnaire and standardized phase angle,
      normalized for gender, age and BMI in 105 patients as independent risk factors
      for outcomes [overall survival (OS), non-relapse mortality (NRM), relapse
      mortality (RM), progression-free survival (PFS)] until 2 years after alloHCT. In
      Cox proportional-hazards regression models, we included a variety of accepted
      risk factors. The two most influential pre-transplant risk factors identified and
      associated with similarly increased hazard ratios (HR) for OS, RM, and PFS were a
      low-standardized phase angle (HR = 1.97, P = 0.043; HR = 3.18, P = 0.017, and HR
      = 1.91, P = 0.039) and advanced disease. Under- and overweight according BMI
      percentiles (<=10th; >=90th) revealed associations with increased risk of NRM (HR
      = 2.90, P = 0.018; HR = 3.02, P = 0.062), although only low BMI was weakly
      associated with OS (HR = 1.82, P = 0.09). In conclusion, our results demonstrate
      that pre-transplant phase angle is an independent predictor for 2-year outcomes
      in these patients. Further investigation is necessary to demonstrate whether the
      theoretically modifiable phase angle can be increased by physical training
      combined with nutritional support, and if this improves outcome after alloHCT.

PMID- 22968662
TI  - Local distal radius bone graft versus iliac crest bone graft for scaphoid
      nonunion: a comparative study.
AB  - The aim of the study is to find whether there is any superiority of the iliac
      crest bone graft over the distal radius bone graft, in surgery of nonunion of
      scaphoid fractures. This is a prospective randomized controlled trial comparing
      50 patients treated with internal fixation and distal radius bone graft (group 1)
      and 50 patients in whom iliac crest bone graft was used instead (group 2). The
      patients donor site pain in the postoperative period was assessed using visual
      analogue scale. At each follow-up, each patient was evaluated using Quick DASH
      score and Mayo's scoring system. Minimum follow-up was 3 years. Mean value of
      visual analogue scale for pain was 7.1 for group 2 and 4.2 for group 1. There was
      no statistically significant difference between the two groups in terms of range
      of wrist joint motion, functional scores, union rate and fracture reduction.
      There is no advantage of the iliac crest over the distal radius graft to justify
      its greater morbidity.

PMID- 22968663
TI  - Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant
      activity and potential applications of milk-derived antioxidative peptides.
AB  - The beneficial effects of food-derived antioxidants in health promotion and
      disease prevention are being increasingly recognized. Recently, there has been a
      particular focus on milk-derived peptides; as a source of antioxidants, these
      peptides are inactive within the sequence of the parent protein but can be
      released during enzyme hydrolysis. Once released, the peptides have been shown to
      possess radical scavenging, metal ion chelation properties and the ability to
      inhibit lipid peroxidation. A variety of methods have been used to evaluate in
      vitro antioxidant activity, however, there is no standardised methodology, which
      hinders comparison of data. This review provides an overview on the generation of
      antioxidative peptides from milk proteins, the proposed mechanisms of
      protein/peptide induced antioxidant activity, in vitro measurement of antioxidant
      activity, in vivo evaluation of plasma antioxidant capacity and the
      bioavailability of antioxidative peptides. The understanding gained from other
      food proteins is referred to where specific data on milk-derived peptides are
      limited. The potential applications and health benefits of antioxidant peptides
      are discussed with a particular focus on the aging population. The regulatory
      requirements for peptide-based antioxidant functional foods are also considered.

PMID- 22968664
TI  - Isoleucine as a possible bridge between exogenous delivery and terrestrial
      enhancement of homochirality.
AB  - We report a highly enantioselective oligomerization of isoleucine stereomers in
      the salt-induced peptide formation reaction under plausibly prebiotic earth
      conditions. Up to 6.5-fold superiority in reactivity of L-isoleucine was
      observed, compared to its D-enantiomer, after 14 evaporation cycles in the
      presence of Cu(2+) and NaCl. Since isoleucine is among the proteinogenic amino
      acids that were found enantioenriched in meteorites, this present work may
      further correlate the extraterrestrial delivery and endogenous production of
      biological homochirality by virtue of a protein constituent rather than the
      rarely occurring alpha-methylated amino acids.

PMID- 22968665
TI  - Supported oligomethionine sulfoxide and Ellman's reagent for cysteine bridges
      formation.
AB  - A large number of bioactive peptides are cyclized through a disulfide bridge.
      This structural feature is very important for both bioactivity and stability. The
      oxidation of cysteine side chains is challenging not only to avoid intermolecular
      reaction leading to oligomers and oxidation of other residues but also to remove
      solvents and oxidant such as dimethyl sulfoxide. Supported reagents
      advantageously simplify the work-up of such disulfide bond formation, but may
      lead to a significant decrease in yield of the oxidized product. In this study,
      two resins working through different mechanisms were evaluated: Clear-Ox, a
      supported version of Ellman's reagent and Oxyfold, consisting in a series of
      oxidized methionine residues. The choice of the supported reagent is discussed on
      the light of reaction speed, side-products formation and yield considerations.

PMID- 22968667
TI  - Fuel cell-powered microfluidic platform for lab-on-a-chip applications:
      Integration into an autonomous amperometric sensing device.
AB  - The present paper reports for the first time the integration of a microfluidic
      system, electronics modules, amperometric sensor and display, all powered by a
      single micro direct methanol fuel cell. In addition to activating the electronic
      circuitry, the integrated power source also acts as a tuneable micropump. The
      electronics fulfil several functions. First, they regulate the micro fuel cell
      output power, which off-gas controls the flow rate of different solutions toward
      an electrochemical sensor through microfluidic channels. Secondly, as the fuel
      cell powers a three-electrode electrochemical cell, the electronics compare the
      working electrode output signal with a set reference value. Thirdly, if the
      concentration measured by the sensor exceeds this threshold value, the
      electronics switch on an integrated organic display. This integrated approach
      pushes forward the development of truly autonomous point-of-care devices relying
      on electrochemical detection.

PMID- 22968666
TI  - Attentional bias for prescription opioid cues among opioid dependent chronic pain
      patients.
AB  - Recurrent use of prescription opioid analgesics by chronic pain patients may
      result in opioid dependence, which involves implicit neurocognitive operations
      that organize and impel craving states and compulsive drug taking behavior. Prior
      studies have identified an attentional bias (AB) towards heroin among heroin
      dependent individuals. The aim of this study was to determine whether opioid
      dependent chronic pain patients exhibit an AB towards prescription opioid-related
      cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of
      non-dependent opioid users with chronic pain (n = 33) completed a dot probe task
      designed to measure opioid AB. Participants also rated their opioid craving and
      self-reported arousal associated with opioid-related and neutral images, pain
      severity, and relief from pain treatments. Repeated-measures ANOVA revealed a
      significant group (opioid-dependent vs. non-dependent opioid user) * presentation
      duration (200. vs. 2,000 ms.) interaction, such that opioid-dependent individuals
      evidenced a significant AB towards opioid cues presented for 200 ms but not for
      cues presented for 2,000 ms, whereas non-dependent opioid users did not exhibit a
      significant mean AB at either stimulus duration. Among opioid-dependent
      individuals, 200 ms opioid AB was significantly associated with opioid craving,
      while among non-dependent opioid users, 200 ms opioid AB was significantly
      associated with relief from pain treatments. Furthermore, dependent and non
      dependent opioid users experienced opioid cues as significantly more arousing
      than neutral cues. Opioid dependence among chronic pain patients appears to
      involve an automatic AB towards opioid-related cues. When coupled with chronic
      pain, attentional fixation on opioid cues may promote compulsive drug use and
      addictive behavior. 

PMID- 22968669
TI  - Drug-induced sleep endoscopy vs awake Muller's maneuver in the diagnosis of
      severe upper airway obstruction.
AB  - OBJECTIVE: To compare fiber-optic nasal endoscopy with Muller's maneuver (FNMM)
      against drug-induced sleep endoscopy (DISE) in diagnosing the presence of severe
      level-specific upper airway collapse in patients with obstructive sleep
      apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Case series with chart review.
      SETTING: Tertiary care academic center. SUBJECTS AND METHODS: Medical records of
      all adult patients undergoing diagnostic DISE as part of their surgical
      evaluation were reviewed. Patients were included if they had undergone FNMM and
      had documented Friedman tongue position and tonsillar grade prior to DISE. Airway
      obstruction on both endoscopic procedures was described according to airway level
      and severity. Severe airway obstruction was defined as >75% collapse on
      endoscopy. RESULTS: Fifty-three patients were included in this study. Fiber-optic
      nasal endoscopy with Muller's maneuver and DISE did not differ significantly
      regarding the presence of severe retropalatal airway collapse. There was a
      statistically significant difference in the incidence of severe retrolingual
      collapse identified via DISE (84.9% [45/53]) compared with FNMM (35.8% [19/53]; P
      < .0001). This discrepancy between FNMM and DISE findings was statistically
      significant in individuals with Friedman I and II tongue positions (FNMM = 16.7%,
      DISE = 88.9%, P < .0001) and individuals with Friedman III tongue position (FNMM
      = 31.8%, DISE = 81.8%, P = .002). Patients with Friedman IV showed no significant
      difference (P = .65) between FNMM (69.2%) and DISE (84.6%). CONCLUSION: This
      study shows a significant difference between FNMM and DISE in the identification
      of severe retrolingual collapse. Since the effectiveness of surgical
      interventions depends largely on the accurate preoperative identification of the
      site of obstruction, further scrutiny of each diagnostic endoscopic technique is
      warranted.

PMID- 22968670
TI  - Palatal implant versus zygoma plate anchorage for distalization of maxillary
      posterior teeth.
AB  - This study aimed to examine the skeletal, dental, and soft tissue effects of the
      implant-supported pendulum (ISP) and the zygoma anchorage system (ZAS) used for
      the distalization of maxillary posterior teeth. Among 30 patients showing Angle
      class II malocclusion, 15 patients with a mean age of 14.3+/-1.6 years and
      treated with ISP were included in the first group; 15 patients with a mean age of
      14.7+/-2.5 years and treated with ZAS were included in the second group. The
      predistalization and postdistalization lateral cephalograms were analysed.
      Statistical evaluation was carried out using SPSS. Point A and upper incisors
      protruded in the ISP group, retruded in the ZAS group. Upper posterior teeth were
      distalized in both groups, but more in the ZAS group. Significant differences
      were observed between the groups for the sagittal movements of Point A, incisors,
      and posterior teeth. Overbite decreased in the ISP group, overjet decreased in
      the ZAS group, upper and lower lips retruded only in the ZAS group. Both methods
      provided absolute anchorage for distalization of posterior teeth, but the
      skeletal and soft tissue outcome and distalization obtained was greater in the
      ZAS group. Both methods can be used as alternatives to extraoral traction and
      conventional molar distalization appliances with different patient requirements. 

PMID- 22968671
TI  - Obscuring surface anatomy in volumetric imaging data.
AB  - The identifying or sensitive anatomical features in MR and CT images used in
      research raise patient privacy concerns when such data are shared. In order to
      protect human subject privacy, we developed a method of anatomical surface
      modification and investigated the effects of such modification on image
      statistics and common neuroimaging processing tools. Common approaches to
      obscuring facial features typically remove large portions of the voxels. The
      approach described here focuses on blurring the anatomical surface instead, to
      avoid impinging on areas of interest and hard edges that can confuse processing
      tools. The algorithm proceeds by extracting a thin boundary layer containing
      surface anatomy from a region of interest. This layer is then "stretched" and
      "flattened" to fit into a thin "box" volume. After smoothing along a plane
      roughly parallel to anatomy surface, this volume is transformed back onto the
      boundary layer of the original data. The above method, named normalized anterior
      filtering, was coded in MATLAB and applied on a number of high resolution MR and
      CT scans. To test its effect on automated tools, we compared the output of
      selected common skull stripping and MR gain field correction methods used on
      unmodified and obscured data. With this paper, we hope to improve the
      understanding of the effect of surface deformation approaches on the quality of
      de-identified data and to provide a useful de-identification tool for MR and CT
      acquisitions.

PMID- 22968672
TI  - Plant communities in relation to flooding and soil characteristics in the water
      level fluctuation zone of the Three Gorges Reservoir, China.
AB  - With the filling of the Three Gorges Reservoir, original vegetation in the water
      level fluctuation zone (WLFZ) between the elevations of 145 and 175 m disappeared
      due to the reversal of submergence time (winter flooding) and prolonged
      inundation duration (nearly half a year). To better understand the relationships
      between the environmental factors and recovered plant communities for
      reconstructing floristically diverse riparian zone, we conducted a field survey
      in 11 sites in the WLFZ in June 2010, and vegetation composition, flooding
      characteristics, heavy metals, and soil major nutrients were determined.
      Consequently, the canonical correspondence analysis was used to investigate the
      relationships between plant species composition and flooding characteristics,
      heavy metal contamination, and soil nutrients. Results demonstrated that
      vegetation in the WLFZ was dominated by annuals, i.e., Echinochloa crusgalli and
      Bidens tripartita, and perennials including Cynodon dactylon, and plant species
      richness and diversity were negatively associated with flooding duration, heavy
      metal contamination, and nutrients including total phosphorus, available
      phosphorus, available potassium, and nitrate. Our results suggest that plant
      species, recovering mainly through soil seed bank and regeneration of remnant
      individuals, have been influenced by the combined effects of environmental
      factors.

PMID- 22968673
TI  - A detailed investigation of ambient aerosol composition and size distribution in
      an urban atmosphere.
AB  - This research was executed between March 2009 and March 2010 to monitor
      particulate matter size distribution and its composition in Istanbul. Particulate
      matter composition was determined using ion chromatography and inductively
      coupled plasma optical emission spectrometry. The sampling point is adjacent to a
      crowded road and the Bosporus Strait. Two prevailing particulate modes are found
      throughout PM10 by sampling with a nine-stage low-volume cascade impactor. First
      mode in the fine mode is found to be between 0.43 and 0.65 MUm, whereas the other
      peak was observed between 3.3 and 4.7 MUm, referring to the coarse mode. The mean
      PM10 concentration was determined as 41.2 MUg/m(3), with a standard deviation of
      16.92 MUg/m(3). PM0.43 had the highest mean concentration value of 10.67
      MUg/m(3), making up nearly one fourth of the total PM10 mass. For determining the
      effect of traffic on particulate matter (PM) composition and distribution, four
      different sampling cycles were applied: entire day, nighttime, rush hour, and
      rush hour at weekdays. SO4(-2) and organic carbon/elemental carbon proportions
      are found to be lower in night samples, representing a decrease in traffic. The
      long-range transports of dust storms were observed during the sampling periods.
      Their effects were determined analytically and their route models were run by the
      HYSPLIT model and validated through satellite photographs taken by the NASA Earth
      Observatory.

PMID- 22968674
TI  - Exogenously applied calcium alleviates cadmium toxicity in Matricaria chamomilla
      L. plants.
AB  - Cadmium (Cd) toxicity in plants leads to serious disturbances of physiological
      processes, such as inhibition of chlorophyll synthesis, oxidative injury to the
      plant cells and water and nutrient uptake. Response of Matricaria chamomilla L.
      to calcium chloride (CaCl(2)) enrichment in growth medium for reducing Cd
      toxicity were studied in this study. Hydroponically cultured seedlings were
      treated with 0, 0.1, 1, and 5 mM CaCl(2), under 0, 120, and 180 MUM CdCl(2)
      conditions, respectively. The study included measurements pertaining to
      physiological attributes such as growth parameters, Cd concentration and
      translocation, oxidative stress, and accumulation of phenolics. Addition of
      CaCl(2) to growth media decreased the Cd concentration, activity of antioxidant
      enzymes, and reactive oxygen species accumulation in the plants treated with
      different CdCl(2), but increased the growth parameters. Malondialdehyde and total
      phenolics in shoots and roots were not much affected when plants were treated
      only with different CaCl(2) levels, but it showed a rapid increase when the
      plants were exposed to 120 and 180 CdCl(2) levels. CaCl(2) amendment also
      ameliorated the CdCl(2)-induced stress by reducing oxidative injury. The
      beneficial effects of CaCl(2) in ameliorating CdCl(2) toxicity can be attributed
      to the Ca-induced reduction of Cd concentration, by reducing the cell-surface
      negativity and competing for Cd(2+) ion influx, activity enhancement of
      antioxidant enzymes, and biomass accumulation.

PMID- 22968676
TI  - Synthesis of cyclic polylactide catalysed by bis(salicylaldiminato)tin(II)
      complexes.
AB  - Eight bis(salicylaldiminato)tin(II) complexes have been synthesized from the
      reaction of Sn[N(SiMe(3))(2)](2) and 2 equiv of the corresponding ligands at room
      temperature. The ligands, synthesized from salicylaldehyde and amines, were
      designed to have different electronic and steric properties using different
      amines to synthesize the tin(II) complexes as aniline (2a), 2,6-dimethylaniline
      (2b), 2,6-diisopropylaniline (2c), 4-methoxyaniline (2d), 4
      trifluoromethylaniline (2e), methylamine (2g), and tert-butylamine (2h). Ligand
      variation at the salicyl group synthesized from 4-bromosalicylaldehyde and 2,6
      diisopropylaniline was used to form complex 2f. Complex 2c was characterized
      crystallographically. All catalysts were active for the neat polymerization of L
      lactide at 115  degrees C. At a lactide : Sn molar ratio of 10 : 1, cyclic
      polylactide (PLA) was obtained as demonstrated by (1)H NMR and mass spectrometry.
      Addition of 1 equiv of benzyl alcohol in the polymerization produced linear PLA.
      At a higher lactide : Sn molar ratio of 200 : 1, high molecular weight PLAs with
      M(n) up to 132,200 Daltons were obtained. Results from GPC coupled with light
      scattering detector and viscometer suggested that they are cyclic PLA. The order
      of reactivity based on conversion was determined to be 2c < 2b < 2a in accordance
      with lower steric hindrance. For electronic contribution, the order of 2e < 2a <
      2d was observed in agreement with the increasing electron donation of the
      ligands. Complex 2g having the smallest substituents was found to be the most
      active catalyst.

PMID- 22968677
TI  - Intragastric balloon for the treatment of obesity: evaluation of pulmonary
      function over a 3-month period.
AB  - BACKGROUND: Obesity has become a global epidemic in the 21st century, and the
      placement of an intragastric balloon (IB) is a therapeutic modality used to treat
      it. Our objectives for this study were to evaluate changes in lung function
      resulting from IB use and to correlate the pattern of body fat distribution with
      changes in lung function. METHODS: This was an interventional study with 30
      overweight and obese patients with metabolic syndrome. All of the subjects
      underwent anthropometric measurements, assessment of their body fat distribution
      pattern by dual-energy X-ray absorptiometry, and pulmonary function testing
      before implantation of the IB. RESULTS: During the initial evaluations, the main
      pulmonary function abnormalities observed were decreased expiratory reserve
      volume (ERV), decreased total lung capacity (TLC), and increased diffusing
      capacity of carbon monoxide (DL(CO)), which occurred in 56.7, 40, and 23.3 % of
      patients, respectively. We observed a statistically significant positive
      correlation between the DL(CO) and the percentage of trunk fat mass (rho = 0.42;
      p < 0.01). Three months after placement of the IB, there was a significant
      reduction in the body mass index (p < 0.0001) and the maximal inspiratory
      pressure (p < 0.009). We also observed a significant increase in the forced vital
      capacity (p < 0.0001), TLC (p < 0.001), and ERV (p < 0.0001). CONCLUSIONS: Weight
      loss as a result of IB causes increased static lung volumes and decreased
      inspiratory muscle strength. Additionally, being overweight and obese is related
      to increased DL(CO), especially in individuals with truncal obesity.

PMID- 22968679
TI  - Kinetics and mechanism of the reaction of OH with the trimethylbenzenes-
      experimental evidence for the formation of adduct isomers.
AB  - The reversible gas-phase addition of OH radicals to the trimethylbenzenes was
      investigated in pulsed experiments utilizing VUV flash-photolysis resonance
      fluorescence of H(2)O in the temperature range of 275-340 K. Triexponential OH
      decays were observed in the presence of the trimethylbenzenes, indicating the
      participation of more than one adduct species. Analytical solutions for the
      system of differential equations with two adduct isomers were derived, and the OH
      decay curves were evaluated based on this reaction model. This led to significant
      improvements of fit qualities and notable changes in OH rate constants compared
      to a previous model with a single adduct species. The detailed analysis was
      confined to 1,3,5-trimethylbenzene where reversible formation of two OH-aromatic
      ortho- and ipso-adduct isomers is feasible in accordance with the extended
      reaction model. Only after inclusion of additional isomerization reactions,
      consistent thermochemical data were obtained from the fitted rate constants.
      Reaction enthalpies of -83 +/- 7 kJ mol(-1) and -35 +/- 22 kJ mol(-1) were
      derived for the formation of one adduct isomer and the isomerization into the
      other, respectively. Based on literature data, the more and less stable adducts
      were assigned to ipso- and ortho-adduct isomers, respectively. The potential
      isomerization precluded the determination of primary yields of adduct isomers but
      formation of the ipso-adduct in any case is a minor process. For the rate
      constants of the OH + 1,3,5-trimethylbenzene reaction an Arrhenius expression
      k(OH) = 1.32 * 10(-11) cm(3) s(-1) exp(450 +/- 50 K/T) was obtained. Based on the
      same approach, the rate constants of the OH reactions with 1,2,3-trimethylbenzene
      and 1,2,4-trimethylbenzene were derived as k(OH) = 3.61 * 10(-12) cm(3) s(-1)
      exp(620 +/- 80 K/T) and k(OH) = 2.73 * 10(-12) cm(3) s(-1) exp(730 +/- 70 K/T),
      respectively.

PMID- 22968678
TI  - Metformin in non-diabetic patients presenting with ST elevation myocardial
      infarction: rationale and design of the glycometabolic intervention as adjunct to
      primary percutaneous intervention in ST elevation myocardial infarction (GIPS)
      III trial.
AB  - BACKGROUND: Left ventricular dysfunction and the development of heart failure is
      a frequent and serious complication of myocardial infarction. Recent animal
      experimental studies suggested that metformin treatment reduces myocardial injury
      and preserves cardiac function in non-diabetic rats after experimental myocardial
      infarction. We will study the efficacy of metformin with the aim to preserve left
      ventricular ejection fraction in non-diabetic patients presenting with ST
      elevation myocardial infarction (STEMI). METHODS: The Glycometabolic Intervention
      as adjunct to Primary percutaneous intervention in ST elevation myocardial
      infarction (GIPS)-III trial is a prospective, single center, double blind,
      randomized, placebo-controlled trial. Three-hundred-and-fifty patients, without
      diabetes, requiring primary percutaneous coronary intervention (PCI) for STEMI
      will be randomized to metformin 500 mg twice daily or placebo treatment and will
      undergo magnetic resonance imaging (MRI) after 4 months. Major exclusion criteria
      were prior myocardial infarction and severe renal dysfunction. The primary
      efficacy parameter is left ventricular ejection fraction 4 months after
      randomization. Secondary and tertiary efficacy parameters include major adverse
      cardiac events, new onset diabetes and glycometabolic parameters, and
      echocardiographic diastolic function. Safety parameters include renal function
      deterioration and lactic acidosis. CONCLUSIONS: The GIPS-III trial will evaluate
      the efficacy of metformin treatment to preserve left ventricular ejection
      fraction in STEMI patients without diabetes.

PMID- 22968680
TI  - Application of the molecularly imprinted solid-phase extraction to the
      organophosphate residues determination in strawberries.
AB  - This study describe an analytical method employing gas chromatography (GC) using
      flame photometric detection that has been developed for the simultaneous
      determination of organophosphate pesticides (diazinon, disulfoton, parathion,
      chlorpyrifos and malathion) in strawberry samples. For this purpose, molecularly
      imprinted solid-phase extraction was applied as a sample preparation technique.
      The method was linear in the ranges from 0.10 to 1.00 MUg g(-1), for diazinon,
      disulfoton, parathion and chlorpyrifos, and 0.10 to 2.00 MUg g(-1) for malathion
      with r > 0.99. The detection limits (LD) ranged from 0.02 to 0.05 MUg g(-1).
      Recovery studies yielded average recoveries in the range of 65.25 to 87.70 %.
      These results showed the potential of this technique for organophosphate residue
      monitoring in strawberry samples.

PMID- 22968681
TI  - New quality-control materials for the determination of alkylphenols and
      alkylphenol ethoxylates in sewage sludge.
AB  - The determination of alkylphenols in sewage sludge is still hindered by the
      complexity of the matrix and of the analytes, some of which are a mixture of
      isomers. Most of the methods published in the literature have not been validated,
      due to the lack of reference materials for the determination of alkylphenols in
      sludge. Given this situation, the objectives of the present study were to develop
      a new quality-control material for determining octylphenol, nonylphenol and
      nonylphenol monoethoxylate in sludge. The material was prepared from an
      anaerobically digested sewage sludge, which was thermally dried, sieved,
      homogenized and bottled after checking for the bulk homogeneity of the processed
      material. Together with the sewage sludge, an extract was also prepared, in order
      to provide a quality-control material for allowing laboratories to test the
      measuring step. The homogeneity and 1-year stability of the two materials were
      evaluated. Statistical analysis proved that the materials were homogeneous and
      stable for at least 1 year stored at different temperatures. These materials are
      intended to assist in the quality control of the determination of alkylphenols
      and alkylphenol ethoxylates in sewage sludge.

PMID- 22968682
TI  - Selective sensing of Hg2+ by a proton-ionizable calix[4]arene fluoroionophore.
AB  - A fluorogenic derivative of a calix[4]arene with two proton-ionizable N
      (phenyl)sulfonyl carboxamide-containing side arms in the 1,3-positions on the
      lower rim is employed for the selective sensing of Hg(2+) at low concentration
      levels in water/MeCN (1:1, v/v) solutions containing Pb(2+) and Cd(2+). All three
      metal ions quench the fluorescence of the ligand in pure MeCN. However, in
      water/MeCN mixed solvent, the recognition of such cations occurs differently as
      only Hg(2+) complexation quenches the fluorescence of the calixarene. Experiments
      carried out in the presence of an acid and a bulky non-complexing cation shows
      that the quenching of the calixarene fluorescence upon Hg(2+) addition is likely
      due to proton displacement from the proton-ionizable side arms of the ligand. The
      system may be employed as a simple tool for the selective and efficient mercury
      sensing in mixed water/organic solvent.

PMID- 22968683
TI  - Occupational exposure to complex mixtures of volatile organic compounds in
      ambient air: desorption from activated charcoal using accelerated solvent
      extraction can replace carbon disulfide?
AB  - A desorption study of 57 volatile organic compounds (VOCs) has been conducted by
      use of accelerated solvent extraction (ASE) and gas chromatography-mass
      spectrometry. Different solvents were tested to extract activated charcoal tubes
      with the objective of replacing carbon disulfide, used in official methods,
      because of its highly toxic health and environmental effects. Extraction
      conditions, for example temperature and number of cycles, were investigated and
      optimized. The definitive extraction procedure selected was use of acetone at 150
      degrees C and two consecutive extraction cycles at a pressure of 1,500 psi.
      Considering a sample volume of 0.005 Nm(3), corresponding to a sampling time of 8
      h at a flow rate of 0.01 L min(-1), the method was validated over the
      concentration range 65-26,300 MUg Nm(-3). The lowest limit of quantification was
      6 MUg Nm(-3), and recovery for the 93 % of analytes ranged from 65 to 102 %. For
      most of the compounds, relative standard deviations were less than 15 % for inter
      and intra-day precision. Uncertainty of measurement was also determined: the
      relative expanded uncertainty was always below 29.6 %, except for
      dichlorodifluoromethane. This work shows that use of friendlier solvent, for
      example acetone, coupled with use of ASE, can replace use of CS(2) for chemical
      removal of VOCs from activated charcoal. ASE has several advantages over
      traditional solvent-extraction methods, including shorter extraction time,
      minimum sample manipulation, high reproducibility, and less extraction
      discrimination. No loss of sensitivity occurs and there is also a salutary effect
      on bench workers' health and on the smell of laboratory air.

PMID- 22968685
TI  - Atomic force microscopy of model lipid membranes.
AB  - Supported lipid bilayers (SLBs) are biomimetic model systems that are now widely
      used to address the biophysical and biochemical properties of biological
      membranes. Two main methods are usually employed to form SLBs: the transfer of
      two successive monolayers by Langmuir-Blodgett or Langmuir-Schaefer techniques,
      and the fusion of preformed lipid vesicles. The transfer of lipid films on flat
      solid substrates offers the possibility to apply a wide range of surface
      analytical techniques that are very sensitive. Among them, atomic force
      microscopy (AFM) has opened new opportunities for determining the nanoscale
      organization of SLBs under physiological conditions. In this review, we first
      focus on the different protocols generally employed to prepare SLBs. Then, we
      describe AFM studies on the nanoscale lateral organization and mechanical
      properties of SLBs. Lastly, we survey recent developments in the AFM monitoring
      of bilayer alteration, remodeling, or digestion, by incubation with exogenous
      agents such as drugs, proteins, peptides, and nanoparticles.

PMID- 22968684
TI  - Chemosensors and biosensors based on polyelectrolyte microcapsules containing
      fluorescent dyes and enzymes.
AB  - The concept of enzyme-assisted substrate sensing based on use of fluorescent
      markers to detect the products of enzymatic reaction has been investigated by
      fabrication of micron-scale polyelectrolyte capsules containing enzymes and dyes
      in one entity. Microcapsules approximately 5 MUm in size entrap glucose oxidase
      or lactate oxidase, with peroxidase, together with the corresponding markers
      Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) dichloride (Ru(dpp)) complex
      and dihydrorhodamine 123 (DHR123), which are sensitive to oxygen and hydrogen
      peroxide, respectively. These capsules are produced by co-precipitation of
      calcium carbonate particles with the enzyme followed by layer-by-layer assembly
      of polyelectrolytes over the surface of the particles and incorporation of the
      dye in the capsule interior or in the multilayer shell. After dissolution of the
      calcium carbonate the enzymes and dyes remain in the multilayer capsules. In this
      study we produced enzyme-containing microcapsules sensitive to glucose and
      lactate. Calibration curves based on fluorescence intensity of Ru(dpp) and DHR123
      were linearly dependent on substrate concentration, enabling reliable sensing in
      the millimolar range. The main advantages of using these capsules with optical
      recording is the possibility of building single capsule-based sensors. The
      response from individual capsules was observed by confocal microscopy as
      increasing fluorescence intensity of the capsule on addition of lactate at
      millimolar concentrations. Because internalization of the micron-sized multi
      component capsules was feasible, they could be further optimized for in-situ
      intracellular sensing and metabolite monitoring on the basis of fluorescence
      reporting.

PMID- 22968686
TI  - Degradation and epimerization of ergot alkaloids after baking and in vitro
      digestion.
AB  - The degradation and epimerization of ergot alkaloids (EAs) in rye flour were
      investigated after baking cookies and subsequently subjecting them to an in vitro
      digestion model. Different steps of digestion were analyzed using salivary,
      gastric, and duodenal juices. The degradation and bidirectional conversion of the
      toxicologically relevant (R)-epimers and the biologically inactive (S)-epimers
      for seven pairs of EAs were determined by a HPLC method coupled with fluorescence
      detection. Baking cookies resulted in degradation of EAs (2-30 %) and a shift in
      the epimeric ratio toward the (S)-epimer for all EAs. The applied digestion model
      led to a selective toxification of ergotamine and ergosine, two ergotamine-type
      EAs. The initial percentage of the toxic (R)-epimer in relation to the total
      toxin content was considerably increased after digestion of cookies. Ergotamine
      and ergosine increased from 32 to 51 % and 35 to 55 %, respectively. In contrast,
      EAs of the ergotoxine type (ergocornine, alpha- and beta-ergocryptine, and
      ergocristine) showed an epimeric shift toward their biologically inactive (S)
      epimers. Further experiments indicated that the selective epimerization of
      ergotamine EAs occurs in the duodenal juice only. These results demonstrate that
      toxification of EAs in the intestinal tract should be taken into consideration.

PMID- 22968687
TI  - Effects of Sb(V) on growth and chlorophyll fluorescence of Microcystis aeruginosa
      (FACHB-905).
AB  - In this study, effects of antimony Sb(V) on growth, pigments content, oxygen
      evolution, and photosystem II (PSII) activity of Microcystis aeruginosa were
      investigated. JIP-test, Q(A)(-) reoxidation kinetic test and S-state test were
      used in this study to study the energy distribution and electron transport in
      PSII. Treatment with Sb(V) at various concentrations ranging from 5 to 100 mg/l
      had long-term effects on growth, pigments content, and oxygen evolution of M.
      aeruginosa. Low concentration of Sb(V) had no significant inhibition of the
      biomass production and PSII activity but inhibited the pigment synthesis. Growth,
      pigments content, oxygen evolution, and PSII activity were seriously inhibited
      when treated by high concentration of Sb(V) (100 mg/l). The target sites of Sb(V)
      toxic effect on the PSII of M. aeruginosa were mainly on the donor side and the
      apparatus in the light-dependent reaction. The quantum yield for photochemistry,
      density of reaction centers and photosynthesis performance index decreased,
      whereas the dissipated energy increased. PSII activity of M. aeruginosa was
      promoted when exposure to 50 mg/l Sb(V) by increasing the density of active
      reaction centers and electron transport after Q(A)(-).

PMID- 22968688
TI  - Takotsubo-cardiomyopathy: a case of extremely fast recovery described by
      multimodality cardiac imaging.

PMID- 22968689
TI  - Exploiting mechanical biomarkers in microfluidics.
AB  - Cellular mechanical properties have been observed to have important implications
      for pathogenesis and pathophysiology. These observations have led to the recent
      development of a unique class of biomarkers: mechanical biomarkers. Compared with
      the traditional biochemical-based biomarkers (e.g., antibodies), mechanical
      biomarkers have many advantages such as label-free, low cost, convenient
      maintenance, and reduced assay time. In the past few years, there has been an
      increasing effort to exploit cellular mechanical biomarkers in microfluidic
      devices. This trend makes sense because microfluidic devices often feature
      structures that have characteristic lengths similar to those of cells, which
      renders them uniquely capable of probing and utilizing mechanical biomarkers. In
      this Focus article, we discuss a few examples of mechanical biomarker-based
      microfluidic applications. We believe that these examples are just the tip of the
      iceberg and that the full potential of mechanical biomarkers in microfluidic
      based diagnostics and therapeutics has yet to be revealed.

PMID- 22968690
TI  - Trends in sigma-hole strengths and interactions of F3MX molecules (M = C, Si, Ge
      and X = F, Cl, Br, I).
AB  - It is well-established that many covalently-bonded atoms of Groups IV-VII have
      directionally-specific regions of positive electrostatic potential (sigma-holes)
      through which they can interact with negative sites. In the case of Group VII,
      this is called "halogen bonding." We have studied two series of molecules: the
      F3MX and, for comparison, the H3MX (M = C, Si and Ge; X = F, Cl, Br and I). Our
      objective was to determine how the interplay between M and X in each molecule
      affects the sigma-holes of both, and consequently their interactions with the
      nitrogen lone pair of HCN. We find that the relative electronegativities of M and
      X are not sufficient to explain their effects upon each other's sigma-holes;
      consideration of charge capacity/polarizability (and perhaps other factors) also
      appears to be necessary. However the results do support the description of normal
      sigma-hole interactions as being largely electrostatically-driven.

PMID- 22968693
TI  - Clear evidence of carcinogenic activity by a whole-leaf extract of Aloe
      barbadensis miller (aloe vera) in F344/N rats.
AB  - Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a
      variety of illnesses; however, only limited data are available on the safety of
      this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice
      to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet
      cell hyperplasia of the large intestine in both species. Based upon this
      observation, 2-year drinking water studies were conducted to assess the
      carcinogenic potential of an Aloe vera whole-leaf extract when administered to
      F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per
      sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in
      the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic
      lesions in both species were confined primarily to the large intestine.
      Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic
      junction, cecum, and ascending and transverse colon were significantly higher
      than controls in male and female rats in the 1 and 1.5% dose groups. There were
      no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of
      rats. Increased incidences of mucosa hyperplasia of the large intestine were
      observed in F344/N rats, and increased incidences of goblet cell hyperplasia of
      the large intestine occurred in B6C3F1 mice. These results indicate that Aloe
      vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice
      and a carcinogen of the large intestine in F344/N rats.

PMID- 22968695
TI  - Disruption of a proto-planetary disc by the black hole at the milky way centre.
AB  - Recently, an ionized cloud of gas was discovered plunging towards the
      supermassive black hole, SgrA*, at the centre of the Milky Way. The cloud is
      being tidally disrupted along its path to closest approach at ~3,100
      Schwarzschild radii from the black hole. Here we show that the observed
      properties of this cloud of gas can naturally be produced by a proto-planetary
      disc surrounding a low-mass star, which was scattered from the observed ring of
      young stars orbiting SgrA*. As the young star approaches the black hole, its disc
      experiences both photoevaporation and tidal disruption, producing a cloud. Our
      model implies that planets form in the Galactic centre, and that tidal debris
      from proto-planetary discs can flag low-mass stars, which are otherwise too faint
      to be detected.

PMID- 22968692
TI  - Targeting ALK: a promising strategy for the treatment of non-small cell lung
      cancer, non-Hodgkin's lymphoma, and neuroblastoma.
AB  - Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a
      number of biological and biochemical functions through normal ligand-dependent
      signaling. It has oncogenic functions in a number of tumors including non-small
      cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when
      altered by translocation or amplification or mutation. On August 2011, a small
      molecule inhibitor against ALK, crizotinib, was approved for therapy against
      NSCLC with ALK translocations. As we determine the molecular heterogeneity of
      tumors, the potential of ALK as a relevant therapeutic target in a number of
      malignancies has become apparent. This review will discuss some of the tumor
      types with oncogenic ALK alterations. The activity and unique toxicities of
      crizotinib are described, along with potential mechanisms of resistance and new
      therapies beyond crizotinib.

PMID- 22968694
TI  - Modulation of inflammatory gene expression by the ribotoxin deoxynivalenol
      involves coordinate regulation of the transcriptome and translatome.
AB  - The trichothecene deoxynivalenol (DON), a common contaminant of cereal-based
      foods, is a ribotoxic mycotoxin known to activate innate immune cells in vivo and
      in vitro. Although it is recognized that DON induces transcription and mRNA
      stabilization of inflammation-associated mRNAs in mononuclear phagocytes, it is
      not known if this toxin affects translation of selected mRNA species in the
      cellular pool. To address this question, we employed a focused
      inflammation/autoimmunity PCR array to compare DON-induced changes in profiles of
      polysome-associated mRNA transcripts (translatome) to total cellular mRNA
      transcripts (transcriptome) in the RAW 264.7 murine macrophage model. Exposure to
      DON at 250 ng/ml (0.84 uM) for 6 h induced robust expression changes in
      inflammatory response genes including cytokines, cytokine receptors, chemokines,
      chemokine receptors, and transcription factors, with 73% of the changes being
      highly comparable within transcriptome and translatome populations. When
      expression changes of selected representative inflammatory response genes in the
      polysome and cellular mRNA pools were quantified in a follow-up study by real
      time PCR, closely coordinated regulation of the translatome and transcriptome was
      confirmed; however, modest but significant differences in the relative expression
      of some genes within the two pools were also detectable. Taken together, DON's
      capacity to alter translation expression of inflammation-associated genes appears
      to be driven predominantly by selective transcription and mRNA stabilization that
      have been reported previously; however, a small subset of these genes appear to
      be further regulated at the translational level.

PMID- 22968696
TI  - A non-syn-gas catalytic route to methanol production.
AB  - Methanol is an important platform molecule for chemical synthesis and its high
      energy density also renders it a good candidate as a cleaner transportation fuel.
      At present, methanol is manufactured from natural gas via the indirect syn-gas
      route. Here we show that ethylene glycol, a versatile chemical derived from
      biomass or fossil fuels, can be directly converted to methanol in hydrogen with
      high selectivity over a Pd/Fe(2)O(3) co-precipitated catalyst. This opens up a
      possibility for diversification in natural resources for energy-starved
      countries. The working catalyst contains extremely small 'PdFe' clusters and
      metal adatoms on defective iron oxide to give the required metal-support
      interaction for the novel synthesis.

PMID- 22968697
TI  - Attention gates visual coding in the human pulvinar.
AB  - The pulvinar nucleus of the thalamus is suspected to have an important role in
      visual attention, based on its widespread connectivity with the visual cortex and
      the fronto-parietal attention network. However, at present, there remain many
      hypotheses on the pulvinar's specific function, with sparse or conflicting
      evidence for each. Here we characterize how the human pulvinar encodes attended
      and ignored objects when they appear simultaneously and compete for attentional
      resources. Using multivoxel pattern analyses on data from two functional magnetic
      resonance imaging (fMRI) experiments, we show that attention gates both position
      and orientation information in the pulvinar: attended objects are encoded with
      high precision, while there is no measurable encoding of ignored objects. These
      data support a role of the pulvinar in distractor filtering--suppressing
      information from competing stimuli to isolate behaviourally relevant objects.

PMID- 22968698
TI  - Enhanced mechanical properties of nanocrystalline boron carbide by nanoporosity
      and interface phases.
AB  - Ceramics typically have very high hardness, but low toughness and plasticity.
      Besides intrinsic brittleness associated with rigid covalent or ionic bonds,
      porosity and interface phases are the foremost characteristics that lead to their
      failure at low stress levels in a brittle manner. Here we show that, in contrast
      to the conventional wisdom that these features are adverse factors in mechanical
      properties of ceramics, the compression strength, plasticity and toughness of
      nanocrystalline boron carbide can be noticeably improved by introducing
      nanoporosity and weak amorphous carbon at grain boundaries. Transmission electron
      microscopy reveals that the unusual nanosize effect arises from the deformation
      induced elimination of nanoporosity mediated by grain boundary sliding with the
      assistance of the soft grain boundary phases. This study has important
      implications in developing high-performance ceramics with ultrahigh strength and
      enhanced plasticity and toughness.

PMID- 22968700
TI  - Real-time in vivo imaging of the beating mouse heart at microscopic resolution.
AB  - Real-time imaging of moving organs and tissues at microscopic resolutions
      represents a major challenge in studying the complex biology of live animals.
      Here we present a technique based on a novel stabilizer setup combined with a
      gating acquisition algorithm for the imaging of a beating murine heart at the
      single-cell level. The method allows serial in vivo fluorescence imaging of the
      beating heart in live mice in both confocal and nonlinear modes over the course
      of several hours. We demonstrate the utility of this technique for in vivo
      optical sectioning and dual-channel time-lapse fluorescence imaging of cardiac
      ischaemia. The generic method could be adapted to other moving organs and thus
      broadly facilitate in vivo microscopic investigations.

PMID- 22968699
TI  - High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer
      risk in several generations of offspring.
AB  - Maternal exposures to environmental factors during pregnancy influence the risk
      of many chronic adult-onset diseases in the offspring. Here we investigate
      whether feeding pregnant rats a high-fat (HF)- or ethinyl-oestradiol (EE2)
      supplemented diet affects carcinogen-induced mammary cancer risk in daughters,
      granddaughters and great-granddaughters. We show that mammary tumourigenesis is
      higher in daughters and granddaughters of HF rat dams and in daughters and great
      granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in
      mammary cancer risk is transmitted to HF granddaughters equally through the
      female or male germ lines, but it is only transmitted to EE2 granddaughters
      through the female germ line. The effects of maternal EE2 exposure on offspring's
      mammary cancer risk are associated with changes in the DNA methylation machinery
      and methylation patterns in mammary tissue of all three EE2 generations. We
      conclude that dietary and oestrogenic exposures in pregnancy increase breast
      cancer risk in multiple generations of offspring, possibly through epigenetic
      means.

PMID- 22968703
TI  - Fabrication of flexible and freestanding zinc chalcogenide single layers.
AB  - Inorganic graphene analogues (IGAs) are a conceptually new class of materials
      with attractive applications in next-generation flexible and transparent
      nanodevices. However, their species are only limited to layered compounds, and
      the difficulty in extension to non-layered compounds hampers their widespread
      applicability. Here we report the fabrication of large-area freestanding single
      layers of non-layered ZnSe with four-atomic thickness, using a strategy involving
      a lamellar hybrid intermediate. Their surface distortion, revealed by means of
      synchrotron radiation X-ray absorption fine structure spectroscopy, is shown to
      give rise to a unique electronic structure and an excellent structural stability,
      thus determining an enhanced solar water splitting efficiency and photostability.
      The ZnSe single layers exhibit a photocurrent density of 2.14 mA cm(-2) at 0.72 V
      versus Ag/AgCl under 300 W Xe lamp irradiation, 195 times higher than that of
      bulk counterpart. This work opens the door for extending atomically thick IGAs to
      non-layered compounds and holds promise for a wealth of innovative applications.

PMID- 22968702
TI  - Proximity-induced high-temperature superconductivity in the topological
      insulators Bi2Se3 and Bi2Te3.
AB  - Interest in the superconducting proximity effect has been reinvigorated recently
      by novel optoelectronic applications as well as by the possible emergence of the
      elusive Majorana fermion at the interface between topological insulators and
      superconductors. Here we produce high-temperature superconductivity in Bi(2)Se(3)
      and Bi(2)Te(3) via proximity to Bi(2)Sr(2)CaCu(2)O(8+delta), to access higher
      temperature and energy scales for this phenomenon. This was achieved by a new
      mechanical bonding technique that we developed, enabling the fabrication of high
      quality junctions between materials, unobtainable by conventional approaches. We
      observe proximity-induced superconductivity in Bi(2)Se(3) and Bi(2)Te(3)
      persisting up to at least 80 K-a temperature an order of magnitude higher than
      any previous observations. Moreover, the induced superconducting gap in our
      devices reaches values of 10 mV, significantly enhancing the relevant energy
      scales. Our results open new directions for fundamental studies in condensed
      matter physics and enable a wide range of applications in spintronics and quantum
      computing.

PMID- 22968701
TI  - TGFbeta induces the formation of tumour-initiating cells in claudinlow breast
      cancer.
AB  - The role of transforming growth factor-beta (TGFbeta) in the progression of
      different molecular subtypes of breast cancer has not been clarified. Here we
      show that TGFbeta increases breast tumour-initiating cell (BTIC) numbers but only
      in claudin(low) breast cancer cell lines by orchestrating a specific gene
      signature enriched in stem cell processes that predicts worse clinical outcome in
      breast cancer patients. NEDD9, a member of the Cas family of integrin scaffold
      proteins, is necessary to mediate these TGFbeta-specific effects through a
      positive feedback loop that integrates TGFbeta/Smad and Rho-actin-SRF-dependent
      signals. In normal human mammary epithelium, TGFbeta induces progenitor activity
      only in the basal/stem cell compartment, where claudin(low) cancers are presumed
      to arise. These data show opposing responses to TGFbeta in both breast malignant
      cell subtypes and normal mammary epithelial cell subpopulations and suggest
      therapeutic strategies for a subset of human breast cancers.

PMID- 22968704
TI  - The spin Hall effect as a probe of nonlinear spin fluctuations.
AB  - The spin Hall effect and its inverse have key roles in spintronic devices as they
      allow conversion of charge currents to and from spin currents. The conversion
      efficiency strongly depends on material details, such as the electronic band
      structure and the nature of impurities. Here we show an anomaly in the inverse
      spin Hall effect in weak ferromagnetic NiPd alloys near their Curie temperatures
      with a shape independent of material details, such as Ni concentrations. By
      extending Kondo's model for the anomalous Hall effect, we explain the observed
      anomaly as originating from the second-order nonlinear spin fluctuation of Ni
      moments. This brings to light an essential symmetry difference between the spin
      Hall effect and the anomalous Hall effect, which reflects the first-order
      nonlinear fluctuations of local moments. Our finding opens up a new application
      of the spin Hall effect, by which a minuscule magnetic moment can be detected.

PMID- 22968705
TI  - Greatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase
      promoting factor.
AB  - Maturation/M-phase-promoting factor is the universal inducer of M-phase in
      eukaryotic cells. It is currently accepted that M-phase-promoting factor is
      identical to the kinase cyclin B-Cdk1. Here we show that cyclin B-Cdk1 and M
      phase-promoting factor are not in fact synonymous. Instead, M-phase-promoting
      factor contains at least two essential components: cyclin B-Cdk1 and another
      kinase, Greatwall kinase. In the absence of Greatwall kinase, the M-phase
      promoting factor is undetectable in oocyte cytoplasm even though cyclin B-Cdk1 is
      fully active, whereas M-phase-promoting factor activity is restored when
      Greatwall kinase is added back. Although the excess amount of cyclin B-Cdk1
      alone, but not Greatwall kinase alone, can induce nuclear envelope breakdown,
      spindle assembly is abortive. Addition of Greatwall kinase greatly reduces the
      amount of cyclin B-Cdk1 required for nuclear envelope breakdown, resulting in
      formation of the spindle with aligned chromosomes. M-phase-promoting factor is
      thus a system consisting of one kinase (cyclin B-Cdk1) that directs mitotic entry
      and a second kinase (Greatwall kinase) that suppresses the protein phosphatase 2A
      B55 which opposes cyclin B-Cdk1.

PMID- 22968706
TI  - Evidence of an inhibitory restraint of seizure activity in humans.
AB  - The location and trajectory of seizure activity is of great importance, yet our
      ability to map such activity remains primitive. Recently, the development of
      multi-electrode arrays for use in humans has provided new levels of temporal and
      spatial resolution for recording seizures. Here, we show that there is a sharp
      delineation between areas showing intense, hypersynchronous firing indicative of
      recruitment to the seizure, and adjacent territories where there is only low
      level, unstructured firing. Thus, there is a core territory of recruited neurons
      and a surrounding 'ictal penumbra'. The defining feature of the 'ictal penumbra'
      is the contrast between the large amplitude EEG signals and the low-level firing
      there. Our human recordings bear striking similarities with animal studies of an
      inhibitory restraint, indicating that they can be readily understood in terms of
      this mechanism. These findings have important implications for how we localize
      seizure activity and map its spread.

PMID- 22968709
TI  - Exciting middle and high school students about immunology: an easy, inquiry-based
      lesson.
AB  - High school students in the United States are apathetic about science,
      technology, engineering and mathematics (STEM), and the workforce pipeline in
      these areas is collapsing. The lack of understanding of basic principles of
      biology means that students are unable to make educated decisions concerning
      their personal health. To address these issues, we have developed a simple,
      inquiry-based outreach lesson centered on a mouse dissection. Students learn key
      concepts in immunology and enhance their understanding of human organ systems.
      The experiment highlights aspects of the scientific method and authentic data
      collection and analysis. This hands-on activity stimulates interest in biology,
      personal health and careers in STEM fields. Here, we present all the information
      necessary to execute the lesson effectively with middle and high school students.

PMID- 22968710
TI  - Iron metabolism in man.
AB  - Iron metabolism in man is a highly regulated process designed to provide iron for
      erythropoiesis, mitochondrial energy production, electron transport, and cell
      proliferation. The mechanisms of iron handling also protect cells from the
      deleterious effects of free iron, which can produce oxidative damage of
      membranes, proteins, and lipids. Over the past decade, several important
      molecules involved in iron homeostasis have been discovered, and their function
      has expanded our understanding of iron trafficking under normal and pathological
      conditions. Physiologic iron metabolism is strongly influenced by inflammation,
      which clinically leads to anemia. Although hepcidin, a small circulating peptide
      produced by the liver, has been found to be the key regulator of iron
      trafficking, molecular pathways of iron sensing that control iron metabolism and
      hepcidin production are still incompletely understood. With this review, we
      provide an overview of the current understanding of iron metabolism, the recently
      discovered regulators of iron trafficking, and a focus on the effects of
      inflammation on the process. 

PMID- 22968707
TI  - Contributions of neutrophils to resolution of mucosal inflammation.
AB  - Neutrophil (PMN) recruitment from the blood stream into surrounding tissues
      involves a regulated series of events central to acute responses in host defense.
      Accumulation of PMN within mucosal tissues has historically been considered
      pathognomonic features of both acute and chronic inflammatory conditions.
      Historically, PMNs have been deemed necessary but detrimental when recruited,
      given the potential for tissue damage that results from a variety of mechanisms.
      Recent work, however, has altered our preconceived notions of PMN contributions
      to inflammatory processes. In particular, significant evidence implicates a
      central role for the PMN in triggering inflammatory resolution. Such mechanisms
      involve both metabolic and biochemical crosstalk pathways during the intimate
      interactions of PMN with other cell types at inflammatory sites. Here, we
      highlight several recent examples of how PMN coordinate the resolution of ongoing
      inflammation, with a particular focus on the gastrointestinal mucosa.

PMID- 22968711
TI  - A binuclear iron-thiolate catalyst for electrochemical hydrogen production in
      aqueous micellar solution.
AB  - The substituted iron-thiolate complex [Fe(2)(MU-bdt)(CO)(4){P(OMe)(3)}(2)]
      (bdt=benzenedithiolate) is an active catalyst for electrochemical hydrogen
      production in aqueous sodium dodecyl sulfate solution, with a high apparent rate
      constant of 4*10(6) M(-1) s(-1). The half-peak potential for catalysis of proton
      reduction is less negative than -0.6 V versus the standard hydrogen electrode at
      pH 3. Voltammetric data are consistent with the rate of electrode reaction
      controlled by diffusion. A mechanism that begins with the rapid protonation of
      the iron-thiolate catalyst is proposed. The Faradaic efficiency in diluted HCl
      solutions is close to 100%, but the catalytic activity decayed after about twelve
      turnovers when electrolysis was carried out in the presence of acetic acid.

PMID- 22968708
TI  - Pulmonary dendritic cell development and antigen acquisition.
AB  - Pulmonary dendritic cells (DCs) constantly sample the tissue and traffic inhaled
      antigens to the lung-draining lymph node where they normally orchestrate an
      appropriate immune response. The dynamic ability of these professional antigen
      presenting cells to promote tolerance or immunity has been intensively studied by
      several groups, including ours. Distinct DC subsets in both lymphoid and non
      lymphoid tissues have been described based on their surface molecule expression
      and location. Current efforts to unravel DC development and function are
      providing insight into the various roles each subset offers the immune system.
      Elucidating DC functions, particularly in the lung, may then allow use of the
      inherent ability of these cells for enhanced vaccine strategies and therapeutics
      for pulmonary infections and diseases.

PMID- 22968712
TI  - Effects of geissoschizine methyl ether, an indole alkaloid in Uncaria hook, a
      constituent of yokukansan, on human recombinant serotonin 7 receptor.
AB  - Effects of seven alkaloids, geissoschizine methyl ether (GM), hirsutine,
      hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine and isocorynoxeine,
      in Uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin(7)
      (5-HT(7)) receptor were investigated using Chinese hamster ovary (CHO) cell
      membranes and human embryonic kidney 293 (HEK293) cells stably expressing the
      human recombinant 5-HT(7) receptor. A competitive binding assay using CHO
      membranes showed that GM (IC(50) = 0.034 MUM) more strongly inhibited the binding
      of the radioligand [(3)H] LSD to 5-HT(7) receptor than the other alkaloids,
      suggesting that GM is bound to 5-HT(7) receptor. Agonistic/antagonistic effects
      of GM (1-50 MUM) on the receptor were evaluated by measuring intracellular cAMP
      levels in HEK239 cells. GM (IC(50) = 6.0 MUM) inhibited 5-HT-induced cAMP
      production in a concentration-dependent manner, as well as the specific 5-HT(7)
      receptor antagonist SB-269970 (0.1-1 MUM). However, GM did not induce
      intracellular cAMP production as 5-HT did. These results suggest that GM has an
      antagonistic effect on 5-HT(7) receptor.

PMID- 22968713
TI  - Decavanadate, decaniobate, tungstate and molybdate interactions with sarcoplasmic
      reticulum Ca(2+)-ATPase: quercetin prevents cysteine oxidation by vanadate but
      does not reverse ATPase inhibition.
AB  - Recently we demonstrated that the decavanadate (V(10)) ion is a stronger Ca(2+)
      ATPase inhibitor than other oxometalates, such as the isoelectronic and
      isostructural decaniobate ion, and the tungstate and molybdate monomer ions, and
      that it binds to this protein with a 1 : 1 stoichiometry. The V(10) interaction
      is not affected by any of the protein conformations that occur during the process
      of calcium translocation (i.e. E1, E1P, E2 and E2P) (Fraqueza et al., J. Inorg.
      Biochem., 2012). In the present study, we further explore this subject, and we
      can now show that the decaniobate ion, [Nb(10) = Nb(10)O(28)](6-), is a useful
      tool in deducing the interaction and the non-competitive Ca(2+)-ATPase inhibition
      by the decavanadate ion [V(10) = V(10)O(28)](6-). Moreover, decavanadate and
      vanadate induce protein cysteine oxidation whereas no effects were detected for
      the decaniobate, tungstate or molybdate ions. The presence of the antioxidant
      quercetin prevents cysteine oxidation, but not ATPase inhibition, by vanadate or
      decavanadate. Definitive V(IV) EPR spectra were observed for decavanadate in the
      presence of sarcoplasmic reticulum Ca(2+)-ATPase, indicating a vanadate reduction
      at some stage of the protein interaction. Raman spectroscopy clearly shows that
      the protein conformation changes that are induced by V(10), Nb(10) and vanadate
      are different from the ones induced by molybdate and tungstate monomer ions.
      Here, Mo and W cause changes similar to those by phosphate, yielding changes
      similar to the E1P protein conformation. The putative reduction of vanadium(V) to
      vanadium(IV) and the non-competitive binding of the V(10) and Nb(10)
      decametalates may explain the differences in the Raman spectra compared to those
      seen in the presence of molybdate or tungstate. Putting it all together, we
      suggest that the ability of V(10) to inhibit the Ca(2+)-ATPase may be at least in
      part due to the process of vanadate reduction and associated protein cysteine
      oxidation. These results contribute to the understanding and application of these
      families of mono- and polyoxometalates as effective modulators of many biological
      processes, particularly those associated with calcium homeostasis.

PMID- 22968714
TI  - Solution-crystallized organic semiconductors with high carrier mobility and air
      stability.

PMID- 22968715
TI  - Repeatless and repeat-based centromeres in potato: implications for centromere
      evolution.
AB  - Centromeres in most higher eukaryotes are composed of long arrays of satellite
      repeats. By contrast, most newly formed centromeres (neocentromeres) do not
      contain satellite repeats and instead include DNA sequences representative of the
      genome. An unknown question in centromere evolution is how satellite repeat-based
      centromeres evolve from neocentromeres. We conducted a genome-wide
      characterization of sequences associated with CENH3 nucleosomes in potato
      (Solanum tuberosum). Five potato centromeres (Cen4, Cen6, Cen10, Cen11, and
      Cen12) consisted primarily of single- or low-copy DNA sequences. No satellite
      repeats were identified in these five centromeres. At least one transcribed gene
      was associated with CENH3 nucleosomes. Thus, these five centromeres structurally
      resemble neocentromeres. By contrast, six potato centromeres (Cen1, Cen2, Cen3,
      Cen5, Cen7, and Cen8) contained megabase-sized satellite repeat arrays that are
      unique to individual centromeres. The satellite repeat arrays likely span the
      entire functional cores of these six centromeres. At least four of the
      centromeric repeats were amplified from retrotransposon-related sequences and
      were not detected in Solanum species closely related to potato. The presence of
      two distinct types of centromeres, coupled with the boom-and-bust cycles of
      centromeric satellite repeats in Solanum species, suggests that repeat-based
      centromeres can rapidly evolve from neocentromeres by de novo amplification and
      insertion of satellite repeats in the CENH3 domains.

PMID- 22968716
TI  - HDT701, a histone H4 deacetylase, negatively regulates plant innate immunity by
      modulating histone H4 acetylation of defense-related genes in rice.
AB  - Histone acetylation and deacetylation play an important role in the modification
      of chromatin structure and regulation of gene expression in eukaryotes. Chromatin
      acetylation status is modulated antagonistically by histone acetyltransferases
      and histone deacetylases (HDACs). In this study, we characterized the function of
      histone deacetylase701 (HDT701), a member of the plant-specific HD2 subfamily of
      HDACs, in rice (Oryza sativa) innate immunity. Transcription of HDT701 is
      increased in the compatible reaction and decreased in the incompatible reaction
      after infection by the fungal pathogen Magnaporthe oryzae. Overexpression of
      HDT701 in transgenic rice leads to decreased levels of histone H4 acetylation and
      enhanced susceptibility to the rice pathogens M. oryzae and Xanthomonas oryzae pv
      oryzae (Xoo). By contrast, silencing of HDT701 in transgenic rice causes elevated
      levels of histone H4 acetylation and elevated transcription of pattern
      recognition receptor (PRR) and defense-related genes, increased generation of
      reactive oxygen species after pathogen-associated molecular pattern elicitor
      treatment, as well as enhanced resistance to both M. oryzae and Xoo. We also
      found that HDT701 can bind to defense-related genes to regulate their expression.
      Taken together, these results demonstrate that HDT701 negatively regulates innate
      immunity by modulating the levels of histone H4 acetylation of PRR and defense
      related genes in rice.

PMID- 22968717
TI  - HapX-mediated iron homeostasis is essential for rhizosphere competence and
      virulence of the soilborne pathogen Fusarium oxysporum.
AB  - Soilborne fungal pathogens cause devastating yield losses and are highly
      persistent and difficult to control. During the infection process, these
      organisms must cope with limited availability of iron. Here we show that the bZIP
      protein HapX functions as a key regulator of iron homeostasis and virulence in
      the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect
      iron uptake but causes derepression of genes involved in iron-consuming pathways,
      leading to impaired growth under iron-depleted conditions. F. oxysporum strains
      lacking HapX are reduced in their capacity to invade and kill tomato (Solanum
      lycopersicum) plants and immunodepressed mice. The virulence defect of DeltahapX
      on tomato plants is exacerbated by coinoculation of roots with a biocontrol
      strain of Pseudomonas putida, but not with a siderophore-deficient mutant,
      indicating that HapX contributes to iron competition of F. oxysporum in the
      tomato rhizosphere. These results establish a conserved role for HapX-mediated
      iron homeostasis in fungal infection of plants and mammals.

PMID- 22968718
TI  - Interfacial kinetics of a model epoxy-amine addition reaction.
AB  - The kinetics of the addition reaction at a solid interface for a model epoxy
      amine system composed of monofunctionalized phenyl glycidyl ether and hexylamine
      was examined. The chemical character for the reaction of this system at the
      interface was the same as that in the bulk, while the physical nature was
      significantly different. Slowing down of the diffusion for the reactants in close
      proximity to the solid interface was also addressed by interfacial selective
      spectroscopy.

PMID- 22968720
TI  - Newer insulins in type 2 diabetes.

PMID- 22968719
TI  - Reliability of Schmeling's stages of ossification of medial clavicular epiphyses
      and its validity to assess 18 years of age in living subjects.
AB  - Nowadays, due to the global increase in migration movements, forensic age
      estimation of living young adults has become an important focus of interest.
      Minors often have no identification documents providing their correct birth
      dates. Establishing the age of majority is therefore fundamental in order to
      determine whether juvenile penal systems or penal systems in force for adults are
      to be applied. Radiological examination of the clavicles is one of the methods
      recommended by the Study Group on Forensic Age Diagnostics. In this retrospective
      study, a sample of chest radiographs of 274 subjects, aged between 12 and 25
      years, was studied according to Schmeling's method in order to examine the
      ossification of both medial clavicular epiphyses. All stage classifications were
      evaluated by five examiners. Intra- and inter-examiner reliability was analysed
      by Cohen's K statistic. Intra-examiner agreement was insufficient for two of the
      experts. Inter-examiner agreement, among the other three operators, was moderate
      (K = 0.509). Study of reliability highlighted difficulties in interpretation, the
      need to select qualified personnel and choice of the best radiographic image in
      order to reduce any anatomic overlaps. Although ossification of the medial
      clavicular epiphyses is recommended to assess whether an individual has already
      reached the age of majority or not, these results suggested that it is very
      difficult to clearly identify the five stages of ossification by using
      conventional chest radiography.

PMID- 22968721
TI  - Early fluid resuscitation in severe trauma.

PMID- 22968723
TI  - Government advisers' suggestions for NHS savings don't add up.

PMID- 22968724
TI  - Payment for medical care should be linked to outcomes that patients value,
      meeting concludes.

PMID- 22968722
TI  - Risks of harms using antifibrinolytics in cardiac surgery: systematic review and
      network meta-analysis of randomised and observational studies.
AB  - OBJECTIVE: To estimate the relative risks of death, myocardial infarction,
      stroke, and renal failure or dysfunction between antifibrinolytics and no
      treatment following the suspension of aprotinin from the market in 2008 for
      safety reasons and its recent reintroduction in Europe and Canada. DESIGN:
      Systematic review and network meta-analysis. DATA SOURCES: A Cochrane review of
      antifibrinolytic treatments was chosen as the starting point for this systematic
      review. Medline, Embase, and the Cochrane register of trials were searched with
      no date restrictions for observational evidence. STUDY SELECTION: Propensity
      matched or adjusted observational studies with two or more of the interventions
      of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no
      treatment) that were carried out in patients undergoing cardiac surgery. DATA
      ANALYSIS: Network meta-analysis was used to compare treatments, and odds ratios
      with 95% credible intervals were estimated. Meta-analyses were carried out for
      randomised controlled trials alone and for randomised controlled trials with
      observational studies. RESULTS: 106 randomised controlled trials and 11
      observational studies (43,270 patients) were included. Based on the results from
      analysis of randomised controlled trials, tranexamic acid was associated on
      average with a reduced risk of death compared with aprotinin (odds ratio 0.64,
      95% credible interval 0.41 to 0.99). When observational data were incorporated,
      comparisons showed an increased risk of mortality with aprotinin on average
      relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98)
      and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of
      renal failure or dysfunction on average relative to all comparators: odds ratio
      0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48
      to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon
      aminocaproic acid. CONCLUSION: Although meta-analyses of randomised controlled
      trials were largely inconclusive, inclusion of observational data suggest
      concerns remain about the safety of aprotinin. Tranexamic and epsilon
      aminocaproic acid are effective alternatives that may be safer for patients.

PMID- 22968725
TI  - "Spin" in media coverage of research can be traced to abstracts.

PMID- 22968726
TI  - New York attorney general investigates energy drink makers.

PMID- 22968727
TI  - New health ministers back further debate on assisted suicide law.

PMID- 22968728
TI  - India drafts new rules to combat organ shortage.

PMID- 22968729
TI  - [Report of the working group for oral pathology].

PMID- 22968730
TI  - [Annual report of the working group on informatics in pathology].

PMID- 22968731
TI  - [Plasticity of WNT signaling activity in colorectal cancer].
AB  - Despite inactivating APC mutations, colorectal cancers express the WNT-effector
      protein beta-catenin in a heterogeneous pattern, with strong nuclear expression
      confined to a fraction of tumor cells, often only at the tumor's leading edge.
      WNT-reporter constructs allow separation of these tumor cells with highest
      WNT/beta-Catenin activity, which also express high levels of several putative
      cancer stem cell antigens. Unexpectedly however, these cells do not show
      exclusive tumorigenicity in xenograft experiments, thus questioning their general
      stemness phenotype. Instead, there appears to be significant plasticity between
      both tumor cells with high and low WNT/beta-Catenin activity because both cell
      types can form tumors which again show mixed populations. Furthermore, WNT/beta
      Catenin activity in colon cancer cells can be modulated by MAPK signaling thus
      revealing a means of how other signaling pathways contribute to WNT signaling
      plasticity in colon cancer.

PMID- 22968732
TI  - [Translational research and diagnostics of melanoma].
AB  - Although early stage malignant melanoma (MM) has a favorable prognosis five year
      survival rate is poor (<10%) in patients suffering from distant metastases. Due
      to molecular typing of MM recently high response rates were achieved in
      metastatic MM by using specific inhibitors directed against the mutated form of
      BRAF kinase, e.g. Vemurafinib and Dabrafinib. Therefore BRAF mutation analysis
      has become standard of care in advanced MM and pathologists are urged to provide
      a quality guaranteed molecular diagnostics. However, squamous neoplasias (e. g.,
      keratoacanthomas) and recurrences of MM mostly within 6 months during targeted
      therapy point to the need of further translational research. Thus new drugs, such
      as MEK inhibitors, based on the MAP-kinase pathway downstream of BRAF have
      already effectively been used. Finally, the impact of molecular characteristics
      in different subtypes of MM (acral, mucosal, uveal) will be discussed with
      respect to their specific mutational spectrum (e.g. cKIT , NRAS , GNAQ).

PMID- 22968733
TI  - [Translational research and diagnostics in lung cancer].
AB  - Lung cancer is the most common malignant disease leading to death worldwide.
      Histologically, it is broadly subcategorized into small cell lung cancer (SCLC)
      and non-small cell lung cancer (NSCLC), with the latter mainly consisting of the
      major entities adenocarcinoma and squamous cell carcinoma. However, molecular
      profiling of various lung cancer entities has revealed major molecular
      differences within distinct histological tumor entities, resulting in the
      integration of molecular alterations in the subclassification of lung cancers.
      These findings can only estimate the genetic complexity of lung tumors. Large
      scale molecular profiling has the potential to identify novel diagnostic,
      prognostic and predictive markers as well as therapeutic targets. Importantly,
      this recently arising categorization of lung carcinomas can be regarded as an
      example for the characterization of malignomas of other organ systems. The
      pioneer model for this molecular subcategorization is the classification of
      malignant lymphomas.

PMID- 22968734
TI  - [Meeting of the working group on gynecological and breast pathology of the German
      Society of Pathology 2012].

PMID- 22968736
TI  - [Meeting report of the working group on Uropathology].

PMID- 22968735
TI  - [Translational research and diagnosis in GIST].
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in
      the digestive tract. In up to 90% of cases, they are characterized by activating
      mutations in the KIT or the PDGFRA gene. GIST represent a paradigm for successful
      targeted treatment with tyrosine kinase inhibitors (TKI). Since the approval of
      the TKI imatinib in 2002 the survival of patients with metastatic GIST has
      tripled. The next logical step was the concept of using imatinib in an adjuvant
      approach, which was recently shown to increase overall survival significantly. In
      both settings, the mutational status has high predictive implications. In detail,
      GIST with KIT exon 11 mutations show the best response rates with partial
      remission rates of up to 80%. In KIT exon 9 mutations, a doubled daily dose of
      800 mg imatinib is now standard. The PDGFRA exon 18 mutation D842V has been shown
      to lead to primary resistance. The treatment strategy in GIST is driven by their
      molecular characterisation. Further research has increased our knowledge on
      resistance mechanisms in solid tumors against TKI. The number of patients with
      secondary resistance due to acquired KIT mutations is increasing with treatment
      duration. Strategies to address this situation are the introduction of novel
      pathway inhibitors targeting different levels of signal transduction pathways,
      such as the mTOR/Akt pathway, the RAS/RAF pathway, histone deacetylation, among
      others. Among the GIST without mutations in the common hot spot regions of KIT
      and PDGFRA, the so-called wildtype GIST, further genomic subgroups have been
      identified. One such subgroup carries inactivating germline mutations in the
      genes encoding succinate dehydrogenase B, C, or D. They are associated with the
      occurrence of paragangliomas, so-called Carney-Stratakis syndrome. Most
      frequently, these GIST are located in the stomach, showing an epithelioid
      phenotype and a multinodular growth pattern. They preferentially occur in young
      females and often show lymph node metastases, the latter being very unusual in
      sporadic GIST. In sporadic Carney's triad additional pulmonary chondromas are
      observed and there are no SDH mutations. Another small subgroup of sporadic GIST
      present with BRAF mutations as an alternative genomic event. Finally, very rare
      kindreds with germline mutations in either KIT or PDGFRA have been described who
      develop multiple GIST and depending on the mutational subtype mastocytosis,
      hyperpigmentation and/or dysphagia. In summary, the molecular characterisation of
      GIST has revolutionized their treatment due to increasing knowledge about the
      high relevance of predictive molecular typing in solid tumors.

PMID- 22968737
TI  - Directional postural responses induced by vibrotactile stimulations applied to
      the torso.
AB  - It has been shown that torso-based vibrotactile feedback significantly reduces
      postural sway in balance-compromised adults during quiet standing and in response
      to perturbations. This study aimed to determine whether vibrotactile stimulations
      applied to different torso locations induced directional postural responses and
      whether torso cutaneous information contributes to body representation. Eleven
      healthy young adults equipped with an inertial measurement unit (IMU) placed on
      the torso were asked to maintain an upright posture with closed eyes. Six
      vibrators (tactors) were placed on the torso in contact with the skin over the
      left and right external oblique, internal oblique, and erector spinae muscles at
      the L4/L5 level. Each tactor was randomly activated four times per location at a
      frequency of 250 Hz for a period of 5 s. The IMU results indicated that vibration
      applied individually over the internal oblique and erector spinae muscles induced
      a postural shift of about one degree oriented in the direction of the
      stimulation, while simultaneous activation of all tactors and activation of
      tactors over external oblique muscles produced insignificant postural effects.
      The root mean square of the sway signal was significantly higher during vibration
      than before or after. However, the center of pressure displacement, measured by a
      force plate, was uninfluenced by any vibration. These results suggest a multi
      joint postural response including a torso inclination associated with vibration
      induced changes in cutaneous information. The directional aspect of vibration
      induced postural shifts suggests that cutaneous information from the stimulated
      areas contributes to proprioception and upper body spatial representation.

PMID- 22968738
TI  - Gaze anticipation during human locomotion.
AB  - During locomotion, a top-down organization has been previously demonstrated with
      the head as a stabilized platform and gaze anticipating the horizontal direction
      of the trajectory. However, the quantitative assessment of the anticipatory
      sequence from gaze to trajectory and body segments has not been documented. The
      present paper provides a detailed investigation into the spatial and temporal
      anticipatory relationships among the direction of gaze and body segments during
      locomotion. Participants had to walk along several mentally simulated complex
      trajectories, without any visual cues indicating the trajectory to follow. The
      trajectory shapes were presented to the participants on a sheet of paper. Our
      study includes an analysis of the relationships between horizontal gaze
      anticipatory behavior direction and the upcoming changes in the trajectory. Our
      findings confirm the following: 1) The hierarchical ordered organization of gaze
      and body segment orientations during complex trajectories and free locomotion.
      Gaze direction anticipates the head orientation, and head orientation anticipates
      reorientation of the other body segments. 2) The influence of the curvature of
      the trajectory and constraints of the tasks on the temporal and spatial
      relationships between gaze and the body segments: Increased curvature resulted in
      increased time and spatial anticipation. 3) A different sequence of gaze
      movements at inflection points where gaze plans a much later segment of the
      trajectory.

PMID- 22968739
TI  - The integration of size and weight cues for perception and action: evidence for a
      weight-size illusion.
AB  - Humans routinely estimate the size and weight of objects. Yet, when lifting two
      objects of equal weight but different size, they often perceive the smaller
      object as being heavier. This size-weight illusion (SWI) is known to have a
      lesser effect on motor control of object lifting. How the nervous system combines
      "weight" and "size" cues with prior experience and whether these cues are
      differentially integrated for perception and sensorimotor action is still not
      fully understood. Therefore, we assessed not only whether the experience of size
      biases weight perception, but also if experience of weight biases the size
      perception of objects. Further, to investigate differences between perceptual and
      motor systems for cue-experience integration, participants haptically explored
      the weight of an object with one hand and then shaped the aperture of their other
      hand to indicate its perceived size. Results-First, next to a SWI, healthy adults
      (N = 21) perceived lighter objects as being smaller and heavier objects as being
      larger, demonstrating a weight-size illusion (WSI). Second, participants were
      more susceptible to either the SWI or WSI. Third, aperture of the non-exploring
      hand was scaled to perceived weight and not to physical size. Hand openings were
      consistently smaller than physical size, with SWI-sensitive participants being
      significantly more affected than WSI-sensitive subjects. We conclude: first, both
      size and weight perceptions are biased by prior experience. Weight perception is
      biased by expectations of size, while size perception is influenced by the
      expectancy of weight. Second, humans have the tendency to use one cue
      predominantly for both types of perception. Third, combining perceived weight
      with expected size influenced hand motor control, while online haptic feedback
      was largely ignored. Finally, we present a processing model underlying the size
      weight cue integration for the perceptual and motor system.

PMID- 22968740
TI  - Clinical, immunological and molecular characterization of DOCK8 and DOCK8-like
      deficient patients: single center experience of twenty-five patients.
AB  - PURPOSE: Autosomal recessive hyper-IgE syndrome is a rare combined
      immunodeficiency characterized by susceptibility to viral infections, atopic
      eczema, high serum IgE and defective T cell activation. The genetic etiologies
      are diverse. Null mutations in DOCK8 and TYK2 are responsible for many cases.
      This study aims to provide a detailed clinical and immunological characterization
      of the disease and explore the underlying genetic defects among a large series of
      patients followed by a single center. The available data might improve our
      understanding of the disease pathogenesis and prognosis. METHODS: Clinical data
      of twenty-five patients diagnosed with AR-HIES were collected. Seventeen patients
      screened for STAT3, TYK2 and DOCK8 mutations. RESULTS: Sinopulmonary infections,
      dermatitis, hepatic disorders, cutaneous and systemic bacterial, fungal and viral
      infections were the most common clinical features. The rate of hepatic disorders
      and systemic infections were high. Twelve patients died with a median age of 10
      years. CMV infection was the only statistically significant predicting factor for
      poor prognosis (early death). Three novel DOCK8 mutations and two large deletions
      were found in thirteen patients. No mutations found in STAT3 or TYK2 genes.
      CONCLUSION: Autosomal recessive hyper-IgE syndrome is a combined immunodeficiency
      disease characterized by high morbidity and mortality rate. The different genetic
      background and environmental factors may explain the more severe phenotypes seen
      in our series. DOCK8 defect is the most common identified genetic cause. Patients
      with no identified genetic etiology are likely to carry mutations in the
      regulatory elements of genes tested or in novel genes that are yet to be
      discovered.

PMID- 22968741
TI  - MIF, MIF alleles, and prospects for therapeutic intervention in autoimmunity.
AB  - Macrophage migration inhibitory factor (MIF) is an innate cytokine whose main
      actions include counter-regulating the immunosuppressive action of
      glucocorticoids and inhibiting activation-induced apoptosis. MIF is encoded in a
      functionally polymorphic locus and human genetic studies have shown significant
      relationships between high-expression MIF alleles, host inflammatory responses,
      and improved clinical outcome from infections. A recently completed candidate
      gene association study in the autoimmune disease systemic lupus erythematosus
      (SLE) indicates that individuals with a high-expression MIF allele have reduced
      incidence of SLE. Among patients with established disease however, those with end
      organ complications have increased frequency of high-expression MIF alleles.
      Plasma MIF levels and Toll-like receptor (TLR) stimulated MIF production also
      reflect the underlying MIF genotype. These data suggest that MIF exerts a dual
      influence on the immunopathogenesis of SLE: high-expression MIF alleles are
      associated with a reduced susceptibility to SLE, perhaps by enhancing clearance
      of autoimmunogenic pathogens; once SLE develops however, low-expression MIF
      alleles protect from ensuing inflammatory end-organ damage. These data thus
      provide an example of the potential evolutionary advantage of maintaining an
      autoimmunity susceptibility gene in the population in that high-expression MIF
      alleles may allow for a maximal anti-infective response despite risk of
      autoimmunity. These results also support the clinical feasibility of
      pharmacologic MIF antagonism as such therapies may be most effectively applied in
      those individuals who, on the basis of their genotype, manifest a MIF dependent
      form of autoimmunity.

PMID- 22968742
TI  - Administration of the cyclic peptide COR-1 in humans (phase I study): ex vivo
      measurements of anti-beta1-adrenergic receptor antibody neutralization and of
      immune parameters.
AB  - AIMS: A novel concept for the treatment of heart failure is the neutralization of
      antibodies against the beta(1)-adrenergic receptor (anti-beta(1)AR-ab). In a rat
      model of autoimmune cardiomyopathy, the cyclic peptide COR-1 (given i.v. once
      monthly) neutralized anti-beta(1)AR-abs and prevented anti-beta(1)AR-ab-induced
      myocardial damage, and completely reverted cardiac dysfunction over 3-6 months.
      METHODS AND RESULTS: A clinical phase I trial was designed as a single-blinded,
      placebo-controlled study. Fifty human volunteers received COR-1 or matching
      placebo as a single i.v. administration with ascending doses (10-240 mg). Primary
      endpoints were safety and tolerability, while the pharmacokinetic profile of COR
      1 was assessed as a secondary endpoint. All five investigated dose groups were
      well tolerated; no drug-related side effects occurred. Pharmacokinetics revealed
      a favourable profile with an almost complete plasma clearance within 60 min after
      administration. Pharmacodynamic investigation showed dose-dependent efficacy with
      almost complete scavenging of pathological anti-beta(1)AR-abs ex vivo at the two
      highest doses. No anti-COR-1 autoantibodies occurred. No other effects on the
      immune system (such as an increase of crucial cytokines) were observed up to 43
      days after drug administration, nor upon incubation of anti-beta(1)AR-ab-positive
      patient blood samples with COR-1 ex vivo. CONCLUSIONS: COR-1 was shown to be safe
      after i.v. administration in vivo; no relevant side effects occurred. Efficacy
      was estimated from ex vivo investigation of the potency to neutralize specific
      anti-beta(1)-AR-abs. TRIAL REGISTRATION: NCT 01043146, Eudra CT 2008-007745-31.

PMID- 22968743
TI  - Influence of documented history of coronary artery disease on outcomes in
      patients admitted for worsening heart failure with reduced ejection fraction in
      the EVEREST trial.
AB  - AIMS: Data on the prognosis of heart failure (HF) patients with coronary artery
      disease (CAD) have been conflicting. We describe the clinical characteristics and
      mode-specific outcomes of HF patients with reduced ejection fraction (EF) and
      documented CAD in a large randomized trial. METHODS AND RESULTS: EVEREST was a
      prospective, randomized trial of vasopressin-2 receptor blockade, in addition to
      standard therapy, in 4133 patients hospitalized with worsening HF and reduced EF.
      Patients were classified as having CAD based on patient-reported myocardial
      infarction (MI) or coronary revascularization. We analysed the characteristics
      and outcomes [all-cause mortality and cardiovascular (CV) mortality/HF
      hospitalization] of patients with and without documented CAD. All events were
      centrally adjudicated. Documented CAD was present in 2353 patients (57%).
      Patients with CAD were older and had more co-morbidities compared with those
      without CAD. Patients with CAD were more likely to receive a beta-blocker, but
      less likely to receive an angiotensin-converting enzyme (ACE) inhibitor or
      aldosterone antagonist (P < 0.01). After risk adjustment, patients with
      documented CAD had similar mortality [hazard ratio (HR) 1.12, 95% confidence
      interval (CI) 0.97-1.30], but were at an increased risk for CV mortality/HF
      hospitalization (HR 1.25, 95% CI 1.12-1.41) due to an increased risk for HF
      hospitalization (HR 1.26, 95% CI 1.10-1.44). Patients with CAD had increased HF-
      and MI-related events, but similar rates of sudden cardiac death. CONCLUSION:
      Documented CAD in patients hospitalized for worsening HF with reduced EF was
      associated with a higher burden of co-morbidities, lower use of HF therapies
      (except beta-blockers), and increased HF hospitalization, while all-cause
      mortality was similar.

PMID- 22968744
TI  - KIF21A mRNA expression in patients with Down syndrome.
AB  - Down syndrome (DS) is a chromosomal disorder caused by chromosome 21 trisomy and
      is the most frequent genetic cause of intellectual disability. The gene for the
      kinesin family member 21A (KIF21A), is a member of the kinesin superfamily
      involved in the anterograde fast axonal transport. In this study, we have
      evaluated the possible differential expression of KIF21A mRNA, by qRT-PCR, in
      peripheral blood leukocytes of DS subjects and it compared with the normal
      population. In the assumption that changes in KIF21A gene expression levels may
      affect the axonal transport and the development of the nervous system of subjects
      with DS. In the present case-control study, KIF21A gene expression was increased
      in 72.72 % of DS samples compared with normal subjects. This finding suggests
      that changes in the expression levels of KIF21A in DS subjects may affect the
      axonal transport and the development of the nervous system.

PMID- 22968746
TI  - Magnetic resonance imaging predictors of surgical outcome in degenerative lumbar
      spinal stenosis.
AB  - PURPOSE: To identify any MRI predictors for surgical outcomes of patients with
      degenerative lumbar spinal stenosis (DLSS) having instrumented posterior
      decompression (IPD) surgery. MATERIALS AND METHODS: Seventy patients with DLSS
      who underwent IPD were reviewed retrospectively. The clinical score of each
      patient was assessed using the JOAS (Japanese Orthopedics Association Scoring)
      system, which is mainly based on the subjective symptoms and physical signs of
      the patients before (JOAS-I) and after (JOAS-II) surgery. Healing rate (HR) was
      calculated as: [(JOAS-II) - (JOAS-I)] * 100/[15 - (JOAS-I)]. HR >50 % was
      considered clinical improvement. Radiological stenosis was assessed on MRI and
      was graded from 0 to 3 at the laminectomy level in terms of thecal sac-nerve root
      compression, foraminal stenosis, and facet degeneration. RESULTS: Mean HR of the
      improved patients (n = 39) was 81.94; HR of the unimproved patients (n = 31) was
      34.75 (p < 0.05). There was no statistical difference in radiological stenosis
      parameters between the two groups (p > 0.05). HR was worse in patients with
      severe facet degeneration. CONCLUSIONS: Surgical outcomes of DLSS depend on
      multiple variables. It is not possible to predict the outcomes by assessing only
      one parameter. The possible outcomes should be analyzed by considering all the
      factors individually.

PMID- 22968747
TI  - Diethyl phthalate enhances expression of SIRT1 and DNMT3a during apoptosis in
      PC12 cells.
AB  - Diethyl phthalate (DEP) works as a phthalate plasticizer and is ubiquitously used
      in personal care products, cosmetics, medical equipment and pharmaceutical
      coating. DEP is considered a potential endocrine disruptor. Previously we found
      DEP-enhanced apoptosis induced by serum deprivation in PC12 cells. However, the
      relationship between DEP and longevity-related factors, sirtuins and epigenetic
      factors (e.g. DNA methyltransferases) remains unclear, because genome
      modification caused by chemical toxicity, sirtuins and epigenetic factors have
      played key roles in abnormal metabolism and development. Here, we investigate
      whether DEP affects sirtuins (SIRT1 and SIRT2) and methyltranferases (DNMT1 and
      DNMT3a) on the apoptosis of PC12 cells. We found that DNMT3a was significantly
      decreased by serum deprivation. However, DNMT3a, DNMT3b and SIRT1 were
      significantly increased under the enhancement of apoptosis induced by serum
      deprivation. These results suggest that SIRT1, DNMT3a and DNMT3b play multiple
      and complex roles in different apoptotic stages. Our results showed DEP triggered
      epigenetic factors on PC12 cells apoptosis under nutrition stress. Finally, our
      results suggest that monitoring epigenetic factors such as DNMT3a, DNMT3b and
      SIRT1 could be a useful tool for chemical toxicity risk assessment.

PMID- 22968758
TI  - Heteropolyacid encapsulation into the MOF: influence of acid particles
      distribution on ethanol conversion in hybrid nanomaterials.
AB  - Hybrid nanomaterials comprising tungsten heteropolyacid (HPW) and iron-based MOF
      BasoliteTM F 300 used as a support were obtained by post-synthesis combination of
      the two components. Samples with increasing HPW loading (20, 50, and 80 wt%) were
      characterised by appropriate physicochemical methods, including nitrogen
      sorption, electron microscopy imaging, FT-IR spectroscopy, sorption microbalance
      and catalytic tests. The acidic protons of the tungsten-based heteropolyacid
      catalysed ethanol conversion depending on location of HPW at either internal or
      external surfaces of the commercial BasoliteTM F 300.

PMID- 22968757
TI  - Hypertension increases with aging and obesity in chimpanzees (Pan troglodytes).
AB  - Cardiovascular disease is a primary cause of morbidity and mortality in captive
      chimpanzees. Four years of blood pressure (BP) data were analyzed from a captive
      former laboratory population of 201 healthy adult chimpanzees with assessment of
      age and obesity on elevated BP. Five different measures of obesity were compared:
      abdominal girth, basal metabolic rate, body-mass index (BMI), body weight, and
      surface area. Systolic BP varied by sex. Obesity did not influence male BP. For
      females, obesity was a significant determinant of BP. The best measure of female
      obesity was basal metabolic rate and the worst was BMI. Median systolic BP of
      healthy weight females (<54.5 kg) was significantly lower (128 mmHg) than
      overweight or obese females (140 mmHg), but both were lower than all males (147
      mmHg). For diastolic BP, neither sex nor any of the five obesity measures was
      significant. But age was highly significant, with geriatric chimpanzees (>30
      years) having higher median diastolic BP (74 mmHg) than young adults of 10-29
      years of age (65 mmHg). By these criteria, 80% of this population is
      normotensive, 7% prehypertensive, and 13% hypertensive. In summary, systolic BP
      intervals required adjustment for obesity among females but not males. Diastolic
      BP required adjustment for advanced age (>=30 years). Use of these reference
      intervals can facilitate timely clinical care of captive chimpanzees.

PMID- 22968761
TI  - Iminium ions as dienophiles in Aza-Diels-Alder reactions: a closer look.
AB  - This review highlights the state of the art of the use of iminium ions as
      dienophiles in Aza-Diels-Alder (ADA) cycloadditions. An historical survey
      spanning the very first discovery of the reaction to modern developments,
      mechanistic studies and synthetic applications of the iminium variant of the ADA
      (iADA) reaction are presented. The discussion is focused on the intermolecular
      and intramolecular versions of the iADA reactions that are conducted in aqueous
      solutions to generate, in situ, the reactive dienophile from an amine
      hydrochloride and either aliphatic or aromatic aldehydes in the presence of a
      variety of dienes. The retro-ADA reaction is also presented as an interesting
      method for the protection of amines. The use of Lewis acid catalysis in these
      reactions was thoroughly studied by the reactions of different amines and
      aldehydes conducted in the presence of lanthanide(III) complexes.

PMID- 22968760
TI  - The effects of reboxetine treatment on depression-like behavior, brain
      neurotrophins, and ERK expression in rats exposed to chronic mild stress.
AB  - Chronic mild stress (CMS) in rats is an established rodent depression model.
      Antidepressants attenuate the depression-like symptoms and prevent the
      biochemical changes caused by stress. In the present study, we examined the
      effect of CMS and the selective norepinephrine reuptake inhibitor (NRI)
      reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal
      and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5
      weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to
      half of the stressed and unstressed groups. Animal behavior following CMS was
      tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring
      sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed
      decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced
      hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment
      reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated
      hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both
      stressed and unstressed rats. In conclusion, our study shows that BDNF, its
      receptor TrkB, and ERK participate in the neurobiological response to chronic
      stress and in the molecular and cellular activities of REB in the hippocampus.

PMID- 22968762
TI  - Triplet exciton dissociation in singlet exciton fission photovoltaics.
AB  - Triplet exciton dissociation in singlet exciton fission devices with three
      classes of acceptors are characterized: fullerenes, perylene diimides, and PbS
      and PbSe colloidal nanocrystals. Using photocurrent spectroscopy and a magnetic
      field probe it is found that colloidal PbSe nanocrystals are the most promising
      acceptors, capable of efficient triplet exciton dissociation and long wavelength
      absorption.

PMID- 22968763
TI  - Homoeology of Thinopyrum junceum and Elymus rectisetus chromosomes to wheat and
      disease resistance conferred by the Thinopyrum and Elymus chromosomes in wheat.
AB  - Thirteen common wheat "Chinese Spring" (CS)-Thinopyrum junceum addition lines and
      three common wheat "Fukuhokomuji"(Fuku)-Elymus rectisetus addition lines were
      characterized and verified as disomic additions of a Th. junceum or E. rectisetus
      chromosome in the wheat backgrounds by fluorescent genomic in situ hybridization.
      Another Fuku-E. rectisetus addition line, A1048, was found to contain multiple
      segregating E. rectisetus chromosomes. Seven partial CS-Th. junceum amphiploids
      were identified to combine 12-16 Th. junceum chromosomes with CS wheat
      chromosomes. The disomic addition lines AJDAj5, 7, 8, 9, and HD3508 were
      identified to contain a Th. junceum chromosome in homoeologous group 1. Two of
      them, AJDAj7 and AJDAj9, had the same Th. junceum chromosome. AJDAj2, 3, and 4
      contained a Th. junceum chromosome in group 2, HD3505 in group 4, AJDAj6 and
      AJDAj11 in group 5, and AJDAj1 probably in group 6. The disomic addition lines
      A1026 and A1057 were identified to carry an E. rectisetus chromosome in group 1
      and A1034 in group 5. E. rectisetus chromosomes in groups 1-6 were detected in
      A1048. The homoeologous group of the Th. junceum chromosome in HD3515 could not
      be determined in this study. Several Th. junceum and E. rectisetus chromosomes in
      the addition lines were found to contain genes for resistance to Fusarium head
      blight, tan spot, Stagonospora nodorum blotch, and stem rust (Ug99 races).
      Understanding of the homoeology of the Th. junceum and E. rectisetus chromosomes
      with wheat will facilitate utilization of the favorable genes on these alien
      chromosomes in wheat improvement.

PMID- 22968765
TI  - Thermally and photo-induced spin crossover behaviour in an Fe(II) imidazolylimine
      complex: [FeL3](ClO4)2.
AB  - Herein we report the synthesis, structure and magnetic properties of
      [FeL(3)](ClO(4))(2), 1, where L is the bidentate ligand N-(4-methoxyphenyl)-1H
      imidazol-2-yl-methanimine. Complex 1 crystallises as the mer-isomer which is
      stabilised by intramolecular pi-pi interactions between the methoxyphenyl 'tail'
      and imidazole 'head' of adjacent ligands centred around Fe(II). The crystal
      lattice is devoid of any significant intermolecular pi-pi interactions between
      neighbouring complexes, although hydrogen bonding between two imidazole N-H
      groups and two perchlorate anions links two adjacent complexes together and
      allows them to buttress up against one another. Structural data collected at 116
      and 292 K suggest a spin-crossover (SCO) behaviour for 1 as Fe-N bond lengths
      increase by ca. 10% at the higher temperature. SCO behaviour is confirmed by
      magnetic susceptibility measurements. The chiT vs. T data reveals a complete and
      reversible SCO for 1 with T(1/2) of 158 K, and this is further confirmed by
      Mossbauer spectroscopy (at 4.2 and 293 K) and variable temperature reflectivity
      measurements. Indeed, upon irradiation with red light (647 nm) at 10 K, 1 shows a
      photo-induced spin-crossover and undergoes full switching between the LS and HS
      states.

PMID- 22968764
TI  - The relationship between maternal and fetal vitamin D, insulin resistance, and
      fetal growth.
AB  - Evidence for a role of vitamin D in maintaining normal glucose homeostasis is
      inconclusive. We sought to clarify the relationship between maternal and fetal
      insulin resistance and vitamin D status. This is a prospective cohort study of 60
      caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD),
      glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks.
      Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall
      width, a marker of fetal adiposity. At delivery birth weight was recorded and
      fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin
      resistance was calculated using the Homeostasis Model Assessment (HOMA) equation.
      We found that those with lower 25-OHD in early pregnancy had higher HOMA indices
      at 28 weeks, (r = -.32, P = .02). No significant relationship existed between
      maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and
      fetal anthropometry or birth weight. The incidence of vitamin D deficiency was
      high at each time point (15%-45%). These findings lend support to routine
      antenatal supplementation with vitamin D in at risk populations.

PMID- 22968766
TI  - Vitamin D and its role in skeletal muscle.
AB  - This review discusses the clinical and laboratory studies that have examined a
      role of vitamin D in skeletal muscle. Many observational studies, mainly in older
      populations, indicate that vitamin D status is positively associated with muscle
      strength and physical performance and inversely associated with risk of falling.
      Clinical trials of vitamin D supplementation in older adults with low vitamin D
      status mostly report improvements in muscle performance and reductions in falls.
      The underlying mechanisms are probably both indirect via calcium and phosphate
      and direct via activation of the vitamin D receptor (VDR) on muscle cells by 1,25
      dihydroxyvitamin D [1,25(OH)(2)D]. VDR activation at the genomic level regulates
      transcription of genes involved in calcium handling and muscle cell
      differentiation and proliferation. A putative membrane-associated VDR activates
      intracellular signaling pathways also involved in calcium handling and signaling
      and myogenesis. Additional evidence comes from VDR knockout mouse models with
      abnormal muscle morphology and physical function, and VDR polymorphisms which are
      associated with differences in muscle strength. Recent identification of CYP27B1
      bioactivity in skeletal muscle cells and in regenerating adult mouse muscle lends
      support to the direct action of both 25-hydroxyvitamin D and 1,25(OH)(2)D in
      muscle. Despite these research advances, many questions remain. Further research
      is needed to fully characterize molecular mechanisms of vitamin D action on
      muscle cells downstream of the VDR, describe the effects on muscle morphology and
      contractility, and determine whether these molecular and cellular effects
      translate into clinical improvements in physical function.

PMID- 22968767
TI  - Palladium-Mediated Surface-Initiated Kumada Catalyst Polycondensation: A Facile
      Route Towards Oriented Conjugated Polymers.
AB  - Palladium-mediated surface-initiated Kumada catalyst transfer polycondensation is
      used to generate poly(3-methyl thiophene) films with controlled thickness up to
      100 nm. The palladium initiator density is measured using cyclic voltammetry and
      a ferrocene-capping agent, where the surface density is found to be 55% (1.1 *
      10(14) molecules per cm(2)). UV-Vis spectroscopy and AFM show increased
      aggregation in palladium-initiated films due to the higher grafting density of
      palladium initiators on the surface. The anisotropy of the P3MT films is
      determined using polarized UV-Vis spectroscopy, which indicates a degree of
      orientation perpendicular to the substrate. Evidence that palladium can maintain
      pi-complexation even at elevated temperatures, is also shown through the
      exclusive intramolecular coupling of both a phenyl and thiophene-based magnesium
      bromide with different dihaloarenes.

PMID- 22968769
TI  - The challenge of producing quality research.

PMID- 22968768
TI  - Role of magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram
      in diagnosis of sporadic Creutzfeldt-Jakob disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia (RPD)
      that can be difficult to identify antemortem, with definitive diagnosis requiring
      tissue confirmation. We describe the clinical, magnetic resonance imaging (MRI),
      cerebrospinal fluid (CSF), and electroencephalogram (EEG) measures of a small
      cohort of 30 patients evaluated for RPD. Clinical and diagnostic measures were
      cross-sectionally obtained from 17 sCJD patients (15 definite, two probable), 13
      non-prion rapidly progressive dementia patients (npRPD), and 18 unimpaired
      controls. In a subset of patients (nine sCJD and nine npRPD) diffusion tensor
      imaging (DTI) measures [fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD), and radial diffusivity (RD)] were also obtained for the
      caudate, corpus callosum, posterior limb of the internal capsule, pulvinar,
      precuneus, and frontal lobe. Differences among groups were assessed by an
      analysis of variance. Compared to npRPD individuals, sCJD patients had cerebellar
      dysfunction, significantly higher CSF tau, "positive" CSF 14-3-3, and
      hyperintensities on diffusion-weighted imaging (DWI) that met previously
      established imaging criteria for sCJD. EEG changes were similar for the two
      groups. In addition, sCJD patients had significant decreases in DTI measures (MD,
      AD, RD but not FA) within the caudate and pulvinar compared to either npRPD
      patients or unimpaired controls. Our results confirm that CSF abnormalities and
      MRI (especially DWI) can assist in distinguishing sCJD patients from npRPD
      patients. Future longitudinal studies using multiple measures (including CSF and
      MRI) are needed for evaluating pathological changes seen in sCJD patients.

PMID- 22968770
TI  - Aftermath of the Supreme Court ruling on health reform.

PMID- 22968771
TI  - An evaluation of learner perception of competency and satisfaction with three
      models of an interdisciplinary surge capacity course.
AB  - Disaster preparation is a major public health issue, and hospitals play a front
      line role in responding to emergencies and disasters. A key concern identified by
      clinicians is one of being overwhelmed by patients but also by their families and
      the general public in the event of a disaster. In response to this concern, an
      online, workplace-based, interprofessional course in surge capacity building was
      developed and delivered to 72 health and allied staff from five acute care and
      community health care organizations. Three versions of the course were evaluated:
      a stand-alone online course; the online course plus a tabletop exercise; and the
      online course plus the tabletop plus an e-simulation exercise. A descriptive
      study, using surveys, was conducted to examine the impact of the online course on
      learners' perceptions of their competency, their interprofessional skills, and
      satisfaction with the two different course delivery options. Learners made
      significant gains in their perceptions of surge and interprofessional practice
      competency after the online course. This study demonstrates that online learning,
      particularly when combined with a tabletop exercise, can be an effective way to
      support surge capacity skills. Further research, regarding simulation and its
      integration with online learning is an important topic for further exploration.

PMID- 22968772
TI  - Pharmacist's role in an interdisciplinary cardiac rehabilitation team.
AB  - The purpose of this study was to determine the impact of pharmacist and pharmacy
      student involvement with an interdisciplinary cardiac rehabilitation program in
      the outpatient setting. The study included 192 patients who were seen following
      discharge from an acute care hospital between June 2008 and September 2010. The
      pharmacy team educated patients on their medications, conducted medication
      reconciliation, and made patient and provider interventions when appropriate. The
      pharmacist met with the cardiac rehabilitation team before these sessions to
      identify areas of focus and concern. The team met again after the sessions to
      reconcile medication lists and identify areas for follow-up. Of the 192 patients
      seen, an intervention was initiated in 157 (81.8%), for a total of 467
      interventions (mean 2.43 interventions/patient). Medication reconciliation
      interventions not requiring a physician response comprised 79.9% of total
      interventions, most commonly involving an over-the-counter medication not
      initially reported (18%). Seventy-six patient interventions and 18 provider
      interventions were also made; of these, 92% of the patient interventions were
      accepted, and 72% of the provider interventions were accepted. The most common
      patient intervention was changing the administration time of a medication
      (36.8%), and the most common provider intervention was avoidance of a significant
      drug interaction (33.3%). Pharmacists can play a vital role as part of an
      interdisciplinary cardiac rehabilitation team to ensure proper adherence to
      cardiac medications and patient safety through patient education and
      interventions.

PMID- 22968773
TI  - Comparison of video and real-time scoring techniques.
AB  - Maintaining consistency and fairness when grading in a clinical setting can be
      difficult with the best method of clinical evaluation remaining unclear.
      Therefore, it is important to develop methods to ensure that instructors are
      scoring their students fairly within professional allied health programs.
      OBJECTIVE: The purpose of this study was to determine the accuracy of scoring
      students in real-time compared to video. METHODS: Subjects consisted of 27
      students enrolled in an allied health professional program. Students were taught
      a psychomotor clinical skill (PCS) and subsequently performed the skill while
      being graded in both real-time and videotape. RESULTS: Investigators provided
      higher scores when assessing students in real-time versus videotaped evaluation
      (p = 0.006, 1-b = 0.812). There was a trend (p = 0.074; 1-b = 0.514) toward
      students' classification (sophomore, junior, or graduate) affecting scoring
      accuracy. CONCLUSION: These findings indicate students receive higher performance
      scores during real-time scoring as opposed to videotape scoring. Inaccurate PCS
      evaluations are perhaps especially noted in students from lower academic
      classifications who tended to make more mistakes.

PMID- 22968774
TI  - Factors associated with sense of community among allied health students.
AB  - Over the last decade, there has been a substantial increase in online education
      in the health professions, as well as growing recognition that teamwork and
      collaboration are essential to success. While the impact of students' sense of
      community on factors such as course satisfaction and retention has been studied
      among college enrollees in general, there is little research exploring this
      concept among allied health students. To address this shortcoming, a convenience
      sample of students enrolled in a large northeastern school of health-related
      professions was surveyed to gather information on their demographics, curriculum
      and selected course attributes, perceived instructor teaching perspectives, and
      sense of community. Univariate analysis indicated that entry-level students
      experienced a greater sense of community than post-professional students.
      Multivariate analysis revealed that instructor-determined factors of encouraging
      discussion, encouraging expression of opinions, and specifying response times
      best predicted sense of community. With all other variables controlled,
      perceptions of community were significantly lower in online courses, among
      students for whom English was their second language, and in courses where
      instructors were perceived as focused primarily on content delivery. This study
      supports promoting selected course and instructor-related attributes associated
      with sense of community in allied health education, with a particular focus on
      both non-native English speakers and post-professional students. Enhancement of
      online courses with strategies that increase instructor presence, better engage
      students, and facilitate interaction also are warranted.

PMID- 22968775
TI  - Health Care Practitioners' perceptions of motivational interviewing training for
      facilitating behaviour change among patients.
AB  - OBJECTIVES: To investigate, qualitatively, practitioners' perceptions of a 1-day
      interactive and applied workshop in motivational interviewing (MI). Specifically,
      participants explored the training's usefulness in supporting perceptions of
      competence, confidence, and attitudes towards facilitating behaviour change among
      patients. METHODS: Ten health practitioners including dieticians, pharmacists,
      nurses, and social workers participated in this qualitative pilot study.
      Participants received a 1-day (7.5 hour) workshop focused on MI. In-depth one-on
      one interviews were conducted prior to the workshop and at 1 and 4 weeks post
      training. Methods were employed throughout to ensure data trustworthiness.
      RESULTS: Pre-workshop themes about facilitating patient behaviour change
      included: persistence; advice-giving; behaviour change as hard work for
      practitioner; low perceived confidence and competence to help; barriers; and
      feelings of frustration. Post-workshop themes included a renewed inspiration and
      motivation to facilitate behaviour change; partnering with patients and giving
      less advice; experiencing a positive perceived impact on the patients; feeling
      that behaviour change is easier and less stressful; enjoying higher levels of
      competence and confidence; and being mindful of practitioner impact. CONCLUSION:
      Participation in the structured, interactive, and applied MI training was deemed
      effective by practitioners dealing with patient behaviour change. Allied health
      care practitioners are in a key position to facilitate health behaviour changes
      that contribute to behaviour-related illness. The integration of similar MI
      trainings for health practitioners should be further explored with a larger
      group.

PMID- 22968776
TI  - Effectiveness of a developmental curricular design to graduate culturally
      competent health practitioners.
AB  - With the goal to facilitate cultural competency development of students enrolled
      in graduate-level health professional education, this study examined the
      effectiveness of a curricular program guided by the Intercultural Developmental
      Continuum (IDC) as measured by the Intercultural Developmental Inventory (IDI).
      The IDI was administered to 17 occupational therapy (OT) students and a control
      group of 25 non-OT health professional students upon matriculation into their
      respective programs of graduate study and again upon completion of 3 years of
      study. OT students participated in a cultural curricular design guided by the
      IDC, while the control group participated in cultural study not guided by the
      IDC. Though OT students did not show a significant change in overall
      developmental orientation mean scores from pre-test to post-test (t = 0.847, p =
      0.41), the results indicate that the designed intercultural curriculum increased
      intercultural competence among those OT students who began their program with the
      monocultural mindset of polarization (an "us vs. them" evaluative viewpoint) and
      moved to the interculturally transitional mindset of minimization (recognizing
      cultural commonalities and elimination of the "us vs. them" mindset). The control
      group showed a significant decrease in developmental orientation mean scores at
      post-test (t = 6.1, p < 0.001). No significant group or group by baseline
      interaction effects were found when comparing overall post-developmental scores
      adjusting for baseline (F = 2.4, p = 0.131). The curriculum design as guided by
      the IDC, though it did not significantly increase overall cultural competency of
      OT students, appears to have mitigated a decrease in competence. Results suggest
      that the cultural challenges that students face appear to be considerable and,
      without targeted, integrated intercultural preparation, can overwhelm new health
      professionals' intercultural capability.

PMID- 22968777
TI  - Examining intercultural sensitivity and competency of physician assistant
      students.
AB  - Training in intercultural competency for health care professionals is necessary
      to bring greater balance to the disparity currently found among those needing
      health care. The purpose of this study was to determine what, if any,
      improvements in cultural competency were measurable in physician assistant (PA)
      students as they matriculated, using the Multicultural Awareness, Knowledge and
      Skills Survey-Revised as a pretest upon program entry and again as a posttest on
      the final day of the program. Ninety-three PA students from four successive
      classes graduating from a private midwest college between 2003 and 2007
      participated in the pre and post measurements. All students were enrolled in
      specific didactic studies and clinical experiences in cultural sensitivity and
      competency. The results demonstrated significant improvement in knowledge
      (pretest 2.63, posttest 2.76, p=0.001) and skills (pretest 2.63, posttest 2.93,
      p<0.001) for all classes combined. The Intercultural Development Inventory was
      administered to the most recent graduating class to further explore these
      results. This cohort showed the highest scores (group mean 3.58 on scale of 1-5)
      in the Minimization developmental stage, which emphasizes cultural commonality
      over cultural distinctions. Enhanced curricular instruction such as exploring
      cultural assessment methods and controversies in health care differences,
      combined with increased clinical experiences with diverse cultures, are
      recommended to help move students past the minimization stage to gain greater
      cultural competency.

PMID- 22968778
TI  - Pediatric stroke in the U.S.: estimates from the kids' inpatient database.
AB  - Stroke among infants and children is generally considered a rare event. However,
      few studies have used national data to characterized pediatric stroke in the U.S.
      OBJECTIVE: The objective of this paper was to profile pediatric stroke using
      national estimates. METHODS: Data from the Kids' Inpatient Database (KID) was
      examined to estimate total number, mean length of stay, mean costs and discharge
      disposition of pediatric stroke in the U.S. in 2000, 2003, and 2006. RESULTS:
      Estimates indicated that more than 2000 children were discharged from U.S.
      hospitals with a diagnosis of stroke in each of the years 2000, 2003 and 2006.
      Among those, more than 1300 were ischemic strokes (IS), approximately 400 were
      subarachnoid hemorrhages (SAH), and more than 400 were intracerebral hemorrhages
      (ICH) in each of the three years. Estimates also indicated that the average
      length of stay (LOS) over the same time period was approximately 7 days for IS,
      more than 11 days for SAH and approximately 11 days for ICH. Approximately 6% of
      children with stroke died in 2000, 7% in 2003 and 5% in 2006. Regardless of year,
      most children were routinely discharged to home with average costs associated
      with their hospital stay substantially greater for SAH compared to ICH and IS.
      CONCLUSIONS: Although pediatric stroke is not common, more than 2000 children and
      infants experienced strokes in 2000, 2003 and 2006 and at a substantial cost.

PMID- 22968779
TI  - Correlates of safety outcomes during patient ambulance transport: a partial test
      of the Haddon matrix.
AB  - The Haddon Matrix has been cited in a recent review of patient safety as a useful
      framework for understanding Emergency Medical Services (EMS) provider and patient
      injury prevention and safety during ambulance response and transport. The
      research goal of this study was to test part of the Haddon matrix, specifically
      variables within the pre-event host and event host cells, for explaining three
      multi-item ambulance-related safety outcomes: i.e., anticipated use of safety
      equipment, securing the patient, and securing the equipment. Complete study data
      were available for 648 EMS professionals who responded to the 2004 Longitudinal
      Emergency Medical Technician Attributes and Demographic Study (LEADS) survey.
      Overall very modest results were found. Specific findings indicated that EMS
      professionals with: lower perceived health, greater intrinsic satisfaction, more
      time in the patient compartment of an ambulance, and greater seatbelt use had
      higher anticipated use of ambulance safety equipment. For the patient being
      secured in an ambulance, the extremely high mean/low score variance resulted in
      only extrinsic satisfaction having a significant positive association. Finally,
      female EMS professionals, those more extrinsically satisfied, not being involved
      in a prior ambulance accident, and greater seatbelt use were related to higher
      frequency of securing ambulance equipment during patient transport.

PMID- 22968780
TI  - Blogging as a tool to promote reflection among dietetic and physical therapy
      students during a multidisciplinary international service-learning experience.
AB  - Service-learning is a guided, structured learning experience that engages
      students in service to a community for the mutual benefit of the student and
      community. There is a growing trend in healthcare to include international
      service-learning experiences in the training curriculum to promote cultural
      competence. A critical element of service-learning is reflection. There have been
      many research studies examining how best to support and facilitate the reflective
      thinking process in students. The purpose of this study was to assess the
      development of reflective thinking among graduate allied health students during
      an interdisciplinary international service-learning experience using a web-based
      collaborative blog. Twelve graduate students-six dietetic interns and six
      physical therapy doctoral students-traveled to Belize for 6 days to provide
      primary healthcare screenings and intervention to a community. Group blogging was
      found to be an effective tool to promote reflection in allied health student and
      short duration service-learning experience developed reflective thinking.

PMID- 22968781
TI  - Differential NMR spectroscopy reactions of anterior/posterior and right/left
      insular subdivisions due to acute dental pain.
AB  - OBJECTIVES: The insular cortex has an important role within the cerebral pain
      circuitry. The aim of this study was to measure metabolic alterations by MR
      spectroscopy due to experimentally induced trigeminal pain in the
      anterior/posterior and right/left insular subdivisions. METHODS: Sixteen male
      volunteers were investigated using magnetic resonance (MR) spectroscopy before,
      during and after experimentally induced dental pain. Biphasic bipolar electric
      current pulses of 1 ms duration were administered based on the subjectively
      determined pain threshold. Volunteers were instructed to rate every stimulus
      using a MR compatible rating scale. RESULTS: Due to the pain stimulation a
      significant absolute increase in glutamate (Glu, F = 6.1; P = 0.001), glutamine
      (Gln, F = 11.2; P = 0.001) as well as glutamate/glutamine (Glx, F = 17.7; P =
      0.001) were observed, whereas myo-inositol (mI, F = 9.5;P = 0.001) showed a
      significant drop. Additionally, these metabolites showed a significant effect
      towards lateralisation, meaning that metabolic concentration differed either in
      left or right insular subdivision. Creatine demonstrated also an absolute
      significant decrease during stimulation (F = 2.8; P = 0.022) with a significant
      anterior-posterior difference (F = 40.7; P = 0.001). CONCLUSIONS: Results confirm
      that the insular cortex is a metabolically high active region in pain processing
      within the brain. Quantitative metabolic changes show that there is a distinct
      but locally diverse neurometabolic activity under acute pain. The known
      cytoarchitectonic subdivisions show different metabolic reactions and give new
      insights into pain-processing physiology.

PMID- 22968782
TI  - Cerebral vein changes in relapsing-remitting multiple sclerosis demonstrated by
      three-dimensional enhanced T2-weighted angiography at 3.0 T.
AB  - OBJECTIVE: To investigate characteristics of the internal cerebral veins (ICVs)
      and their main tributaries and the deep medullary veins (DMVs) in patients with
      relapsing-remitting MS (RRMS) with enhanced T (2)-weighted angiography imaging
      (ESWAN). METHODS: Fifty-three RRMS patients and 53 normal controls underwent
      conventional MRI and ESWAN. ESWAN venograms were created by performing minimum
      intensity projections of the phase images, and the resulting venograms were used
      to observe characteristic vascular changes, including scores of the ICVs and
      their main tributaries and manifestations of the DMVs. Two experienced
      radiologists analysed all data. RESULTS: Patients showed decreased mean scores of
      the ICVs and their main tributaries compared with controls. The mean score in
      acute patients was higher than in stable patients. Furthermore, the DMVs
      diminished and shortened in 48 patients with longer disease duration, whereas the
      DMVs increased and elongated in 5 patients with shorter disease duration. The
      penetrating veins were well defined in 30 active lesions, whereas the veins were
      ill defined in 69 non-active lesions. Interestingly, well-defined penetrating
      veins were shown in 15 non-active lesions in the stable patients. CONCLUSIONS:
      Enhanced T (2)-weighted MR angiography can detect cerebral vein characteristics
      in relapsing-remitting MS patients, which may provide important information on
      the pathogenesis of MS.

PMID- 22968783
TI  - Nanoleakage in primary teeth prepared by laser irradiation or bur.
AB  - The aim of this in vitro study was to analyze hybrid layer and nanoleakage of
      composite resin restorations in cavities prepared by either Er,Cr:YSGG laser or
      bur, followed by acid etching in primary teeth. Ten extracted primary molar teeth
      were randomly allocated into two groups consisting of ten cavities according to
      surface treatment regimen: Er,Cr:YSGG laser + acid etching(group 1) and bur +
      acid etching(group 2). Restorations of all samples were completed. Then, teeth
      were sectioned and immersed to ammoniacal silver nitrate solution. After
      polishing, hybrid layer thicknesses were examined under scanning electron
      microscopy (SEM) and ion analysis was carried out with SEM/energy dispersive X
      ray spectroscopy preparation in terms of nanoleakage. Hybrid layer thickness and
      the amount of silver ions were assessed for the acid-etched groups. The collected
      data were analyzed with independent sample t test and Spearman's rank
      correlation. In groups 1 and 2, the mean hybrid layer thicknesses were 4.25 +/-
      1.41 and 5.24 +/- 1.07 MUm and the silver ion percentages were 10.97 +/- 13.81
      and 22.79 +/- 21.62 %, respectively. Although no significant correlation was
      observed between the increase of hybrid layer thickness and the amount of silver
      ions, more silver ions were observed in group 2 (p < 0.05). According to the
      results of this study, acid-etched cavities prepared with laser promoted better
      results when compared to the acid-etched cavities prepared with bur. 

PMID- 22968784
TI  - Sequestration of aristolochic acid I from Aristolochia pilosa by Mapeta
      xanthomelas Walker, 1863.
AB  - Sequestration of secondary plant chemicals and brightly colored bodies occur in a
      number of unpalatable insects. The utilization of toxic plant chemicals has been
      proposed as a strategy of chemical defense, while aposematic coloration may
      advertise unpalatability. Here, we tested for the presence of aristolochic acid I
      in leaves of Aristolochia pilosa and female bodies of Mapeta xanthomelas,
      obtained from larvae feeding on the plant, using high performance liquid
      chromatography with photodiode array detection and electrospray ionization mass
      spectrometry. The presence of aristolochic acid I in females of this conspicuous
      diurnal moth, an oligophagous herbivore of Aristolochia, is the first report of
      sequestration of aristolochic acids by an herbivore other than a species of
      Papilionidae.

PMID- 22968786
TI  - Hand-rearing wild caribou calves for studies of nutritional ecology.
AB  - Caribou (Rangifer tarandus) are considered difficult to hand-rear in captivity
      because they are sensitive to the composition and volume of formulated milks. We
      used a strict feeding schedule and a commercial milk formula designed
      specifically for caribou to bottle-feed neonates captured from five wild caribou
      herds in Alaska. Under a feeding protocol adjusted for age and mass, the growth
      rates and body mass of 26 hand-reared caribou calves to weaning were similar to
      those of three maternally nursed caribou. This protocol allows caretakers to hand
      rear caribou that are as representative as possible of maternally raised
      neonates.

PMID- 22968787
TI  - Prevalence of Batrachochytrium dendrobatidis infection is extremely low in direct
      developing Australian microhylids.
AB  - The emerging infectious disease chytridiomycosis has been implicated in declines
      and disappearances of amphibian populations around the world. However,
      susceptibility to infection and the extent of pathological effects of infection
      vary among hosts, and species with life histories that include parental care of
      direct-developing terrestrial eggs may tend to be less susceptible. We examined
      samples from a total of 595 individuals of 9 species of direct-developing
      Australian frogs in the family Microhylidae for the presence of infection by
      Batrachochytrium dendrobatidis (Bd). Between 1995 and 2004, 336 samples were
      collected; 102 of these were analysed histologically and 234 were tissues stored
      in alcohol, which were examined using diagnostic quantitative PCR (qPCR). Swab
      samples were collected from 259 frogs from 2005 to 2008 and were examined using
      qPCR. None of the 595 samples showed evidence of infection by Bd. If these data
      are regarded as a single sample representative of Australian microhylids, the
      upper 95% binomial confidence limit for the prevalence of infection in frogs of
      this family is 0.0062 (<1%). Even if only the data from the more powerful
      diagnostic qPCR tests are used, the upper 95% confidence limit for prevalence is
      0.0075 (<1%). Our data suggest that Australian microhylids have a very low
      prevalence of infection by Bd in nature, and thus are either not susceptible, or
      are only slightly susceptible, to chytridiomycosis. This could be due solely to,
      or in combination with, low rates of transmission and to factors that promote
      resistance to infection, including ecological or behavioural characteristics,
      innate immune functions such as antimicrobial skin peptides, or antimicrobial
      symbionts in skin flora.

PMID- 22968785
TI  - Inhibition of Neu-induced mammary carcinogenesis in transgenic mice expressing
      ERDelta3, a dominant negative estrogen receptor alpha variant.
AB  - The estrogen receptor alpha (ERalpha) splicing variant with an in-frame deletion
      of exon 3 (ERDelta3) is frequently expressed in the normal breast, but its
      influence on tumorigenesis has not been explored. In vitro, ERDelta3 has dominant
      negative activity, suggesting it may suppress estrogen stimulation in the breast.
      ERDelta3 may inhibit classical signaling on estrogen response element (ERE)
      regulated genes as well as activate non-classical pathways at Sp1 and AP-1 sites.
      Transgenic mice were developed that express mouse ERDelta3 in all tissues
      examined, including the mammary gland. To investigate if ERDelta3 expression
      affects tumorigenesis, ERDelta3 mice were crossbred with MMTV-Neu mice. Mammary
      tumor onset was significantly delayed in ERDelta3/Neu versus MMTV-Neu females and
      metastatic incidence and burden was significantly reduced. Consequently, ERDelta3
      expression suppressed tumor development and metastasis in this aggressive model
      of HER2/Neu-positive breast cancer. To determine if ER ligands with anticancer
      activity may augment ERDelta3 protection, the bitransgenic mice were treated with
      tamoxifen and soy isoflavones starting at age 2 months. Soy protein with
      isoflavones (181 mg/1,800 kcal) did not affect tumor development in MMTV-Neu or
      ERDelta3/Neu mice; however, metastatic progression was not inhibited in soy
      treated ERDelta3/Neu mice, as it was in untreated ERDelta3/Neu mice. In contrast,
      tamoxifen (20 mg/1,800 kcal) significantly enhanced tumor prevention in
      ERDelta3/Neu versus MMTV-Neu mice (98% vs. 81% tumor free). The results in
      ERDelta3/Neu mice demonstrate that ERDelta3 influences estrogen-dependent mammary
      carcinogenesis and, thus, may be protective in women expressing ERDelta3 in the
      breast. However, exposure to different estrogens may augment or block its
      beneficial effects.

PMID- 22968788
TI  - Host invasion by Batrachochytrium dendrobatidis: fungal and epidermal
      ultrastructure in model anurans.
AB  - The chytridiomycete fungus Batrachochytrium dendrobatidis (Bd) colonizes
      mouthparts of amphibian larvae and superficial epidermis of post-metamorphic
      amphibians, causing the disease chytridiomycosis. Fungal growth within host cells
      has been documented by light and transmission electron microscopy; however, entry
      of the fungus into host cells has not. Our objective was to document how Bd
      enters host cells in the wood frog Lithobates sylvaticus, a species at high
      mortality risk for chytridiomycosis, and the bullfrog L. catesbeianus, a species
      at low mortality risk for chytridiomycosis. We inoculated frogs and documented
      infection with transmission electron microscopy. Zoospores encysted on the skin
      surface and produced morphologically similar germination tubes in both host
      species that penetrated host cell membranes and enabled transfer of zoospore
      contents into host cells. Documenting fungal and epidermal ultrastructure during
      host invasion furthers our understanding of Bd development and the pathogenesis
      of chytridiomycosis.

PMID- 22968789
TI  - Susceptibility of juvenile Macrobrachium rosenbergii to different doses of high
      and low virulence strains of white spot syndrome virus (WSSV).
AB  - As some literature on the susceptibility of different life stages of
      Macrobrachium rosenbergii to white spot syndrome virus (WSSV) is conflicting, the
      pathogenesis, infectivity and pathogenicity of 2 WSSV strains (Thai-1 and Viet)
      were investigated here in juveniles using conditions standardized for Penaeus
      vannamei. As with P. vannamei, juvenile M. rosenbergii (2 to 5 g) injected with a
      low dose of WSSV-Thai-1 or a high dose of WSSV-Viet developed comparable clinical
      pathology and numbers of infected cells within 1 to 2 d post-infection. In
      contrast, a low dose of WSSV-Viet capable of causing mortality in P. vannamei
      resulted in no detectable infection in M. rosenbergii. Mean prawn infectious dose
      50% endpoints (PID50 ml-1) determined in M. rosenbergii were in the order of 100
      fold higher for WSSV-Thai-1 (105.3 +/- 0.4 PID50 ml-1) than for WSSV-Viet (103.2
      +/- 0.2 PID50 ml-1), with each of these being about 20-fold and 400-fold lower,
      respectively, than found previously in P. vannamei. The median lethal dose (LD50
      ml-1) determined in M. rosenbergii was also far higher (~1000-fold) for WSSV-Thai
      1 (105.4 +/- 0.4 LD50 ml-1) than for WSSV-Viet (102.3 +/- 0.3 LD50 ml-1). Based
      on these data, it is clear that juvenile M. rosenbergii are susceptible to WSSV
      infection, disease and mortality. In comparison to P. vannamei, however, juvenile
      M. rosenbergii appear more capable of resisting infection and disease,
      particularly in the case of a WSSV strain with lower apparent virulence.

PMID- 22968790
TI  - New pathological condition in cultured mulloway Argyrosomus japonicus:
      histopathological, ultrastructural and molecular studies.
AB  - Mulloway Argyrosomus japonicus is a native fish species in Western Australia, for
      which aquaculture production has recently been developed. A single cohort was
      stocked in a cage offshore at Geraldton, Western Australia, at a water depth of 6
      m. Fish appeared healthy before stocking. Routine histological analysis was
      carried out from 10 mo post stocking and until completion of harvest (about 2.5
      yr post stocking). No gross pathology was evident. Microscopically, however,
      granulomatous lesions were present in the kidneys of almost 100% of the fish
      examined. Enclosed in the granuloma was an aggregate of organisms, 4.2 to 5.4 um
      in diameter. Kidney granulomas appeared as multi-focal aggregates. Granulomas at
      different stages of formation and finally fibrosing granulomas were observed.
      Granulomas also appeared infrequently in other organs: a few granulomas were
      found in the liver and spleen and a single granuloma in the heart of one fish.
      Transmission electron microscopy (TEM) revealed that the organism was composed of
      2 cells, an outer cell enclosing an inner cell. The inner cell was surrounded by
      a double membrane and the outer cell by a single membrane. Cellular material,
      presumably of parasitic nature, surrounded the outer cell. The organism contained
      primitive mitochondria and abundant free ribosomes. Small subunit ribosomal DNA
      (SSU rDNA) sequence obtained by PCR revealed an 84% sequence identity with the
      myxosporean Latyspora scomberomori. Based on TEM and preliminary molecular
      results, we suggest that the organism is the extrasporogonic developmental stage
      of a myxozoan parasite, which failed to form spores in the mulloway host.

PMID- 22968791
TI  - Comparison of the Myxobolus fauna of common barbel from Hungary and Iberian
      barbel from Portugal.
AB  - We compared Myxobolus infection of common barbel Barbus barbus from the Danube
      River in Hungary with that in Iberian barbel Luciobarbus bocagei from the Este
      River in Portugal. In Hungary, we recorded 5 known Myxobolus species (M.
      branchialis, M. caudatus, M. musculi, M. squamae, and M. tauricus) and described
      M. branchilateralis sp. n. In Portugal we recorded 6 Myxobolus species (M.
      branchialis, M. branchilateralis sp. n., M. cutanei, M. musculi, M. pfeifferi,
      and M. tauricus). Species found in the 2 habitats had similar spore morphology
      and only slight differences were observed in spore shape or measurements. All
      species showed a specific tissue tropism and had a definite site selection. M.
      branchialis was recorded from the lamellae of the gills, large plasmodia of M.
      branchilateralis sp. n. developed at both sides of hemibranchia, M. squamae
      infected the scales, plasmodia of M. caudatus infected the scales and the fins,
      and M. tauricus were found in the fins and pin bones. In the muscle, 3 species,
      M. musculi, M. pfeifferi and M. tauricus were found; however they were found in
      distinct locations. Plasmodia of M. musculi developed intracellularly in muscle
      cells, plasmodia of M. tauricus were found in the dense connective tissue of the
      pin bones, whereas M. pfeifferi formed plasmodia in the connective tissue of the
      intramuscular septa. This latter species was often found in the cartilaginous
      gill arch as well. Comparative morphological and phylogenetic studies, as well as
      18S rDNA sequences, revealed differences between the Myxobolus fauna of the 2
      barbel species originating from different geographic regions.

PMID- 22968792
TI  - Global coral disease prevalence associated with sea temperature anomalies and
      local factors.
AB  - Coral diseases are taking an increasing toll on coral reef structure and
      biodiversity and are important indicators of declining health in the oceans. We
      implemented standardized coral disease surveys to pinpoint hotspots of coral
      disease, reveal vulnerable coral families and test hypotheses about climate
      drivers from 39 locations worldwide. We analyzed a 3 yr study of coral disease
      prevalence to identify links between disease and a range of covariates, including
      thermal anomalies (from satellite data), location and coral cover, using a
      Generalized Linear Mixed Model. Prevalence of unhealthy corals, i.e. those with
      signs of known diseases or with other signs of compromised health, exceeded 10%
      on many reefs and ranged to over 50% on some. Disease prevalence exceeded 10% on
      20% of Caribbean reefs and 2.7% of Pacific reefs surveyed. Within the same coral
      families across oceans, prevalence of unhealthy colonies was higher and some
      diseases were more common at sites in the Caribbean than those in the Pacific.
      The effects of high disease prevalence are potentially extensive given that the
      most affected coral families, the acroporids, faviids and siderastreids, are
      among the major reef-builders at these sites. The poritids and agaricids stood
      out in the Caribbean as being the most resistant to disease, even though these
      families were abundant in our surveys. Regional warm temperature anomalies were
      strongly correlated with high disease prevalence. The levels of disease reported
      here will provide a much-needed local reference point against which to compare
      future change.

PMID- 22968793
TI  - Interspecific transmission and recovery of TCBS-induced disease between
      Acanthaster planci and Linckia guildingi.
AB  - The susceptibility of the coral-feeding crown-of-thorns starfish Acanthaster
      planci to disease may provide an avenue with which to effectively control
      population outbreaks that have caused severe and widespread coral loss in the
      Indo-Pacific. Injecting thiosulfate-citrate-bile-sucrose (TCBS) agar into A.
      planci tissues induced a disease characterized by dermal lesions, loss of skin
      turgor, collapsed spines, and accumulation of mucus on spine tips. Moreover, the
      symptoms (and presumably the agent) of this disease would spread rapidly
      intraspecifically, but interspecific transmission (to other species of
      echinoderms) is yet to be examined. Vibrio rotiferianus, which was previously
      reported as a pathogen isolated from lesions of experimentally infected A.
      planci, was also recovered from Linckia guildingi lesions after several days of
      direct contact with diseased A. planci, demonstrating disease transmission.
      However, all L. guildingi fully recovered after 31 +/- 16 d. Further studies are
      in progress to understand the ecology of Vibrio infection in A. planci and the
      potential transmission risk to corals, fishes, and other echinoderms to evaluate
      whether injections of TCBS could be a viable tool for controlling A. planci
      outbreaks.

PMID- 22968794
TI  - Phage particles infecting branchial Rickettsiales-like organisms in banded carpet
      shell Polititapes virgineus (Bivalvia) from Galicia (NW Spain).
AB  - Basophilic intracellular prokaryotic-like colonies were observed in the gills of
      banded carpet shell Polititapes virgineus (= Tapes rhomboides) (Linnaeus, 1767)
      from a natural bed in Galicia (NW Spain). Light microscope observations suggested
      the presence of 2 types of colonies, but transmission electron microscopy
      revealed that these were the same Rickettsiales-like colonies, one infected and
      the other uninfected by phage particles. This is the first report of the presence
      of phage particles in Rickettsiales-like organisms in the gills of P. virgineus.

PMID- 22968795
TI  - Simulation-based training for cardiac auscultation skills: systematic review and
      meta-analysis.
AB  - OBJECTIVES: The current review examines the effectiveness of simulation-based
      medical education (SBME) for training health professionals in cardiac physical
      examination and examines the relative effectiveness of key instructional design
      features. METHODS: Data sources included a comprehensive, systematic search of
      MEDLINE, EMBASE, CINAHL, PsychINFO, ERIC, Web of Science, and Scopus through May
      2011. Included studies investigated SBME to teach health profession learners
      cardiac physical examination skills using outcomes of knowledge or skill. We
      carried out duplicate assessment of study quality and data abstraction and pooled
      effect sizes using random effects. RESULTS: We identified 18 articles for
      inclusion. Thirteen compared SBME to no-intervention (either single group pre
      post comparisons or SBME added to other instruction common to all learners, such
      as traditional bedside teaching), three compared SBME to other educational
      interventions, and two compared two SBME interventions. Meta-analysis of the 13
      no-intervention comparison studies demonstrated that simulation-based instruction
      in cardiac auscultation was effective, with pooled effect sizes of 1.10 (95 % CI
      0.49-1.72; p < 0.001; I(2) = 92.4 %) for knowledge outcomes and 0.87 (95 % CI
      0.52-1.22; p < 0.001; I(2) = 91.5 %) for skills. In sub-group analysis, hands-on
      practice with the simulator appeared to be an important teaching technique.
      Narrative review of the comparative effectiveness studies suggests that SBME may
      be of similar effectiveness to other active educational interventions, but more
      studies are required. LIMITATIONS: The quantity of published evidence and the
      relative lack of comparative effectiveness studies limit this review.
      CONCLUSIONS: SBME is an effective educational strategy for teaching cardiac
      auscultation. Future studies should focus on comparing key instructional design
      features and establishing SBME's relative effectiveness compared to other
      educational interventions.

PMID- 22968796
TI  - Colorectal cancer screening: what do women from diverse ethnic groups want?
AB  - BACKGROUND: Little is known about factors associated with willingness to undergo
      colorectal cancer (CRC) screening for personal or public health benefit among
      women from diverse race/ethnic groups. OBJECTIVE: To evaluate factors associated
      with willingness to undergo CRC screening for personal and public health benefit
      among women from diverse race/ethnic groups. METHODS: We interviewed women aged
      50 to 80 from four racial/ethnic groups from primary care clinics in 2003-2005.
      We asked about demographics, CRC screening knowledge and history, perceived risk
      of colon cancer, and about the outcomes of intention to be screened for personal
      benefit and for public health benefit. RESULTS: Of the 492 women who completed
      the interview, 32 % were White, 16 % were African American, 21 % were Latina and
      32 % were Asian. Up-to-date screening was reported by 77 % of women, with similar
      numbers obtaining fecal occult blood test (FOBT) within 2 years or colonoscopy
      within 10 years. The majority of women were "likely or very likely" to get FOBT
      or colonoscopy after learning the benefits and risks. Multivariate models showed
      that compared to Whites, fewer Asians would undergo colonoscopy (OR = 0.28; 95 %
      CI: 0.12, 0.63), while more Latinas would undergo colonoscopy (OR = 6.14; 95 %
      CI: 1.77, 21.34) and obtain regular CRC screening (OR = 4.47; 95 % CI: 1.66,
      12.04). The majority would obtain CRC screening even if they would not personally
      benefit; those who perceived themselves to be at higher than average cancer risk
      were more likely to participate in CRC screening for public health benefit (OR =
      2.32; 95 % CI: 1.32, 4.09). CONCLUSIONS: The majority of women are willing to
      undergo screening for personal benefit. Asians were less likely, and Latinas more
      likely, to accept colonoscopy. Most are also willing to undergo screening for
      public health benefit. Self-perceived risk of CRC was the most consistent
      predictor of willingness and intention to be screened for either personal or
      public health benefit.

PMID- 22968798
TI  - Mothers' and fathers' ratings of family relationship quality: associations with
      preadolescent and adolescent anxiety and depressive symptoms in a clinical
      sample.
AB  - This study examined the independent associations among three family relationship
      quality factors--cohesion, expressiveness, and conflict--with youth self-reported
      depressive and anxiety symptoms in a clinical sample of anxious and depressed
      youth. Ratings of family relationship quality were obtained through both mother
      and father report. The sample included families of 147 preadolescents and
      adolescents (56.6 % female; 89.8 % Caucasian), 11-18 years old (M = 13.64, SD =
      1.98) assigned a principal diagnosis of an anxiety or depressive disorder. When
      controlling for age and concurrent anxiety symptoms, regression analyses revealed
      that for boys, both father- and mother-rated family cohesion predicted depressive
      symptoms. For girls, mother-rated family expressiveness and conflict predicted
      depressive symptoms. Youth anxiety symptoms were not significantly associated
      with any family relationship variables, controlling for concurrent depressive
      symptoms. Findings suggest that parent-rated family relationship factors may be
      more related to youth depressive than anxiety symptoms in this clinical sample.
      In addition, family cohesion, as perceived by parents, may be more related to
      boys' depression, whereas expressiveness and conflict (as rated by mothers) may
      be more related to girls' depression. Clinical implications and recommendations
      for future research are discussed.

PMID- 22968799
TI  - Cross-informant agreement on child and adolescent withdrawn behavior: a latent
      class approach.
AB  - Withdrawn behavior (WB) relates to many developmental outcomes, including
      pervasive developmental disorders, anxiety, depression, psychosis, personality
      disorders and suicide. No study has compared the latent profiles of different
      informants' reports on WB. This study uses multi-informant latent class analyses
      (LCA) of the child behavior checklist (CBCL), teacher report form (TRF) and youth
      self-report (YSR) to examine phenotypic variance in WB. LCA was applied to the
      CBCL, TRF and YSR of 2,031 youth (ages 6-18); of which 276 children were
      clinically-referred. A 4-class solution for the CBCL and 3-class solutions for
      the YSR and TRF were optimal. The CBCL yielded low symptoms, predominantly shy or
      secretive moderate symptoms, and all symptoms classes. The TRF lacked the
      moderate--secretive class, and the YSR lacked the moderate--shy class. Agreement
      was low. LCA shows similar structure of withdrawn behavior across informants but
      characterizations of moderate WB vary.

PMID- 22968800
TI  - Chaperone discovery.
AB  - Molecular chaperones assist de novo protein folding and facilitate the refolding
      of stress-denatured proteins. The molecular chaperone concept was coined nearly
      35 years ago, and since then, tremendous strides have been made in understanding
      how these factors support protein folding. Here, we focus on how various
      chaperone proteins were first identified to play roles in protein folding.
      Examples are used to illustrate traditional routes of chaperone discovery and
      point out their advantages and limitations. Recent advances, including the
      development of folding biosensors and promising methods for the stabilization of
      proteins in vivo, provide new routes for chaperone discovery.

PMID- 22968801
TI  - Multiple states of dimeric aggregates formed by (amido-ethynyl)helicene bidomain
      compound and (amido-ethynyl-amido)helicene tridomain compound.
AB  - An (amido-ethynyl)helicene bidomain compound and an (amido-ethynyl-amido)helicene
      tridomain compound were synthesized. The multidomain compounds were designed on
      the basis of previous findings that amido and ethynyl oligomers form dimeric
      aggregates with properties orthogonal to each other. Four aggregate states of
      multidomain compounds, namely, all-dimer, amido-dimer, ethynyl-dimer, and random
      coil states, were obtained in different solvents, which were analyzed by circular
      dichroism (CD), UV/Vis, (1)H NMR, and IR spectroscopy; vapor pressure osmometry
      (VPO); dynamic light scattering (DLS); and atomic force microscopy (AFM). The
      amido and ethynyl domains independently aggregated and disaggregated in a two
      state manner. Reversible structural changes occurred for a tridomain compound
      between the ethynyl-dimer/random-coil state and the all-dimer/amido-dimer state
      with heating and cooling. Two structural change processes with different
      properties were obtained using a single compound.

PMID- 22968802
TI  - Pharmacological validation of early and late phase of rat mono-iodoacetate model
      using the Tekscan system.
AB  - BACKGROUND: Previous pharmacological validations of the rat mono-iodoacetate
      (MIA)-induced chronic joint pain model were mostly performed by measuring weight
      bearing (WB) deficit with an incapacitance tester. However, conventional
      incapacitance testers have several drawbacks including restrain stress on animal
      and sole use of hind limbs WB. OBJECTIVES: The aim of the present study was to
      compare pharmacological sensitivity of the early (up to 1 week after MIA) versus
      late (between 2 and 4 weeks after MIA) phase of the rat MIA model using a highly
      sensitive tactile pressure measurement system (Tekscan((r))), which can measure
      weight borne by all four limbs and the tail in a non-restrained animal. METHODS:
      The Tekscan((r)) WB measurement system was used in MIA rats to examine the acute
      and chronic dosing effects of drugs that targeted different mechanisms.
      Electrophysiological recordings from joint afferents and biochemical analysis of
      synovial fluid were also performed. RESULTS: Dexamethasone, duloxetine and
      morphine significantly alleviated WB deficits in the Tekscan((r)) system during
      both early and late phase of the MIA model while celecoxib and naproxen
      alleviated WB deficit only during the early phase. Similarly, naproxen was able
      to inhibit spontaneous neuronal activity from MIA joint afferents only during the
      early phase. Finally, concentrations of prostaglandin E(2) in synovial fluid were
      elevated only during the early phase of the rat MIA model. CONCLUSIONS: Our
      pharmacological validation studies using the Tekscan((r)) system along with
      electrophysiological and biochemical results suggest different mechanisms for
      early and late phase of MIA-induced chronic joint pain in rat.

PMID- 22968808
TI  - N-type colloidal-quantum-dot solids for photovoltaics.
AB  - N-type PbS colloidal-quantum-dot (CQD) films are fabricated using a controlled
      halide chemical treatment, applied in an inert processing ambient environment.
      The new materials exhibit a mobility of 0.1 cm(2)  V(-1)  s(-1) . The halogen
      ions serve both as a passivating agent and n-dope the films via substitution at
      surface chalcogen sites. The majority electron concentration across the range
      10(16)  to 10(18)  cm(-3)  is varied systematically.

PMID- 22968809
TI  - Continuous evolution profiles for electronic-tongue-based analysis.

PMID- 22968810
TI  - TOPS: an internet-based system to prevent healthy subjects from over-volunteering
      for clinical trials.

PMID- 22968811
TI  - Effect of the CYP3A inhibitor ketoconazole on the PXR-mediated induction of CYP3A
      activity.
AB  - PURPOSE: The aim of this clinical study was to investigate a previously proposed
      mechanism of ketoconazole-mediated inhibition of cytochrome P450 3A (CYP3A)
      induction. METHODS: A two-phase, randomized, cross-over, open, mono-centre trial
      was carried out. Participants received ketoconazole and St John's wort for 8 days
      to study the proposed suppression of St John's wort-mediated induction of CYP3A
      at the transcriptional level. In the second phase, we studied the inhibitory
      effect of a single dose of ketoconazole directly at the enzyme level during CYP3A
      induction by St John's wort. Midazolam served as a marker substance of CYP3A
      activity using an established limited sampling strategy. RESULTS: After 8 days of
      simultaneous ketoconazole and St John's wort administration, CYP3A-mediated
      midazolam metabolism was strongly inhibited (81 % decrease in clearance).
      Following the induction of CYP3A with St John's wort (6.6-fold increase in
      clearance on day 8), a single dose of ketoconazole strongly inhibited midazolam
      metabolism to the same degree (82 % decrease in clearance in relation to
      baseline). An induction of midazolam metabolism was observed after
      discontinuation of both drugs in both study phases. These results apparently
      contradict the in vitro results where ketoconazole showed an inhibitory effect on
      the transcription of CYP3A genes. CONCLUSIONS: Ketoconazole is a strong inhibitor
      of CYP3A, also when used concomitantly with St John's wort. In therapeutic doses
      it does not inhibit pregnane X receptor-mediated induction of CYP3A in vivo.

PMID- 22968812
TI  - Ghrelin increases GABAergic transmission and interacts with ethanol actions in
      the rat central nucleus of the amygdala.
AB  - The neural circuitry that processes natural rewards converges with that engaged
      by addictive drugs. Because of this common neurocircuitry, drugs of abuse have
      been able to engage the hedonic mechanisms normally associated with the
      processing of natural rewards. Ghrelin is an orexigenic peptide that stimulates
      food intake by activating GHS-R1A receptors in the hypothalamus. However, ghrelin
      also activates GHS-R1A receptors on extrahypothalamic targets that mediate
      alcohol reward. The central nucleus of the amygdala (CeA) has a critical role in
      regulating ethanol consumption and the response to ethanol withdrawal. We
      previously demonstrated that rat CeA GABAergic transmission is enhanced by acute
      and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to
      detect Ghsr mRNA in the CeA and performed electrophysiological recordings to
      measure ghrelin effects on GABA transmission in this brain region. Furthermore,
      we examined whether acute or chronic ethanol treatment would alter these
      electrophysiological effects. Our qRT-PCR studies show the presence of Ghsr mRNA
      in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of
      evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature
      inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further
      increased the ghrelin-induced enhancement of IPSP amplitude, but to a lesser
      extent than ethanol alone. When applied alone, ethanol significantly increased
      IPSP amplitude, but this effect was attenuated by the application of ghrelin. In
      neurons from chronic ethanol-treated (CET) animals, the magnitude of ghrelin
      induced increases in IPSP amplitude was not significantly different from that in
      naive animals, but the ethanol-induced increase in amplitude was abolished.
      Superfusion of the GHS-R1A antagonists D-Lys3-GHRP-6 and JMV 3002 decreased
      evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. D
      Lys3-GHRP-6 and JMV 3002 also blocked ghrelin-induced increases in GABAergic
      responses. Furthermore, D-Lys3-GHRP-6 did not affect ethanol-induced increases in
      IPSP amplitude. These studies implicate a potential role for the ghrelin system
      in regulating GABAergic transmission and a complex interaction with ethanol at
      CeA GABAergic synapses.

PMID- 22968813
TI  - Interaction between behavioral and pharmacological treatment strategies to
      decrease cocaine choice in rhesus monkeys.
AB  - Behavioral and pharmacotherapeutic approaches constitute two prominent strategies
      for treating cocaine dependence. This study investigated interactions between
      behavioral and pharmacological strategies in a preclinical model of cocaine vs
      food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen
      venous catheter, initially responded under a concurrent schedule of food delivery
      (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1
      mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with
      saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently,
      the FR response requirement for cocaine or food was varied (food, FR 100;
      cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine
      on cocaine vs food choice were redetermined. Decreases in the cocaine FR or
      increases in the food FR resulted in leftward shifts in the cocaine choice dose
      effect curve, whereas increases in the cocaine FR or decreases in the food FR
      resulted in rightward shifts in the cocaine choice dose-effect curve. The
      efficacy of phenmetrazine to decrease cocaine choice varied systematically as a
      function of the prevailing response requirements, such that phenmetrazine
      efficacy was greatest when cocaine choice was maintained by relatively low unit
      cocaine doses. These results suggest that efficacy of pharmacotherapies to
      modulate cocaine use can be influenced by behavioral contingencies of cocaine
      availability. Agonist medications may be most effective under contingencies that
      engender choice of relatively low cocaine doses.

PMID- 22968814
TI  - Epigenetic mechanisms for the early environmental regulation of hippocampal
      glucocorticoid receptor gene expression in rodents and humans.
AB  - Parental care influences development across mammals. In humans such influences
      include effects on phenotypes, such as stress reactivity, which determine
      individual differences in the vulnerability for affective disorders. Thus, the
      adult offspring of rat mothers that show an increased frequency of pup
      licking/grooming (ie, high LG mothers) show increased hippocampal glucocorticoid
      receptor (GR) expression and more modest hypothalamic-pituitary-adrenal responses
      to stress compared with the offspring of low LG mothers. In humans, childhood
      maltreatment associates decreased hippocampal GR expression and increased stress
      responses in adulthood. We review the evidence suggesting that such effects are
      mediated by epigenetic mechanisms, including DNA methylation and
      hydroxymethylation across GR promoter regions. We also present new findings
      revealing associated histone post-translational modifications of a critical GR
      promoter in rat hippocampus. Taken together these existing evidences are
      consistent with the idea that parental influences establish stable phenotypic
      variation in the offspring through effects on intracellular signaling pathways
      that regulate the epigenetic state and function of specific regions of the
      genome.

PMID- 22968815
TI  - Gestational methylazoxymethanol exposure leads to NMDAR dysfunction in
      hippocampus during early development and lasting deficits in learning.
AB  - The N-methyl-D-aspartate (NMDA) receptor has long been associated with learning
      and memory processes as well as diseased states, particularly in schizophrenia
      (SZ). Additionally, SZ is increasingly recognized as a neurodevelopmental
      disorder with cognitive impairments often preceding the onset of psychosis.
      However, the cause of these cognitive deficits and what initiates the
      pathological process is unknown. Growing evidence has implicated the glutamate
      system and, in particular, N-methyl-D-aspartate receptor (NMDAR) dysfunction in
      the pathophysiology of SZ. Yet, the vast majority of SZ-related research has
      focused on NMDAR function in adults leaving the role of NMDARs during development
      uncharacterized. We used the prenatal methylazoxymethanol acetate (MAM, E17)
      exposure model to determine the alterations of NMDAR protein levels and function,
      as well as associated cognitive deficits during development. We found that MAM
      exposed animals have significantly altered NMDAR protein levels and function in
      the juvenile and adolescent hippocampus. Furthermore, these changes are
      associated with learning and memory deficits in the Morris Water Maze. Thus, in
      the prenatal MAM-exposure SZ model, NMDAR expression and function is altered
      during the critical period of hippocampal development. These changes may be
      involved in disease initiation and cognitive impairment in the early stage of SZ.

PMID- 22968816
TI  - Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional
      MRI phenotypes in healthy volunteers.
AB  - Genetic variants in GPR85 (SREB2: rs56080411 and rs56039557) have been associated
      with risk for schizophrenia. Here, we test the hypothesis that these variants
      impact on brain function in normal subjects, measured with functional magnetic
      resonance imaging (fMRI) paradigms that target regions with greatest SREB2
      expression (hippocampal formation and amygdaloid complex). During a facial
      emotion recognition paradigm, a significant interaction of rs56080411 genotype by
      sex was found in the left amygdaloid complex (male risk allele carriers showed
      less activation than male homozygotes for the non-risk allele, while females
      showed the opposite pattern). During aversive encoding of an emotional memory
      paradigm, we found that risk allele carriers for rs56080411 had greater
      activation in the right inferior frontal gyrus. Trends in the same direction were
      present for rs56039557 in the right occipital cortex and right fusiform gyrus.
      During a working memory paradigm, a significant sex-by-genotype interaction was
      found with male risk allele carriers of rs56080411 having inefficient activation
      within the left dorsolateral prefrontal cortex (DLPFC), compared with same sex
      non-risk carriers, while females revealed an opposite pattern, despite similar
      levels of performance. These data suggest that risk-associated variants in SREB2
      are associated with phenotypes similar to those found in patients with
      schizophrenia in the DLPFC and the amygdala of males, while the pattern is
      opposite in females. The findings in females and during the emotional memory
      paradigm are consistent with modulation by SREB2 of brain circuitries implicated
      in mood regulation and may be relevant to neuropsychiatric conditions other than
      schizophrenia.

PMID- 22968817
TI  - Occupancy of brain dopamine D3 receptors and drug craving: a translational
      approach.
AB  - Selective dopamine D(3) receptor (D(3)R) antagonists prevent reinstatement of
      drug-seeking behavior and decrease the rewarding effects of contextual cues
      associated with drug intake preclinically, suggesting that they may reduce drug
      craving in humans. GSK598809 is a selective D(3)R antagonist recently progressed
      in Phase I trials. The aim of this study was to establish a model, based on the
      determination of the occupancy of brain D(3)Rs (O(D(3))(R)) across species, to
      predict the ability of GSK598809 to reduce nicotine-seeking behavior in humans,
      here assessed as cigarette craving in smokers. Using ex vivo [(125)I](R)-trans-7
      hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino] tetralin ([(125)I]7OH-PIPAT)
      autoradiography and [(11)C]PHNO positron emission tomography, we demonstrated a
      dose-dependent occupancy of the D(3)Rs by GSK598809 in rat, baboon, and human
      brains. We also showed a direct relationship between O(D(3))(R) and
      pharmacokinetic exposure, and potencies in line with the in vitro binding
      affinity. Likewise, GSK598809 dose dependently reduced the expression of nicotine
      induced conditioned place preference (CPP) in rats, with an effect proportional
      to the exposure and O(D(3))(R) at every time point, and 100% effect at O(D(3))(R)
      values ?72%. In humans, a single dose of GSK598809, giving submaximal levels (72
      89%) of O(D(3))(R), transiently alleviated craving in smokers after overnight
      abstinence. These data suggest that either higher O(D(3))(R) is required for a
      full effect in humans or that nicotine-seeking behavior in CPP rats only
      partially translates into craving for cigarettes in short-term abstinent smokers.
      In addition, they provide the first clinical evidence of potential efficacy of a
      selective D(3)R antagonist for the treatment of substance-use disorders.

PMID- 22968818
TI  - Long-lasting increase of corticosterone after fear memory reactivation:
      anxiolytic effects and network activity modulation in the ventral hippocampus.
AB  - Pathological fear and anxiety can be studied, in rodents, with fear conditioning
      and exposure to reminder cues. These paradigms are thought to critically involve
      the ventral hippocampus, which also serves as key site of glucocorticoid action
      in the brain. Here, we demonstrate a long-lasting reduction of kainate-induced
      gamma oscillations in slice preparations of the ventral hippocampal area CA3, 30
      days after a single fear conditioning training. Reduction of gamma power was
      sensitive to corticosterone application and associated with a decrease in
      glucocorticoid and mineralocorticoid receptor mRNA expression across strata of
      the ventral hippocampal CA3. A fear reactivation session 24 h after the initial
      conditioning normalized receptor expression levels and attenuated the
      corticosterone-mediated recovery of gamma oscillations. It moreover increased
      both baseline and stimulus-induced corticosterone plasma levels and evoked a
      generalization of fear memory to the background context. Reduced ventral
      hippocampal gamma oscillation in both fear reactivated and non-reactivated mice
      were associated with a decrease of anxiety-like behavior in an elevated plus
      maze. Taking advantage of the circadian fluctuation in corticosterone, we
      demonstrated the association of high endogenous basal corticosterone plasma
      concentrations during morning hours with reduced anxiety-like behavior in fear
      reactivated mice. The anxiolytic effect of the hormone was verified with local
      applications to the ventral hippocampus. Our data suggest that corticosterone
      acting on ventral hippocampal network activity has anxiolytic-like effects
      following fear exposure, highlighting its potential therapeutic value for anxiety
      disorders.

PMID- 22968820
TI  - Decreased FANCJ caused by 5FU contributes to the increased sensitivity to
      oxaliplatin in gastric cancer cells.
AB  - BACKGROUND: Oxaliplatin is effective against many types of cancer, and the
      combination of 5-fluorouracil (5FU) and oxaliplatin is synergistically effective
      against gastric cancer, as well as colon cancer. The FANCJ protein is one of the
      Fanconi anemia (FA) gene products, and its interaction with the tumor suppressor
      BRCA1 is required for DNA double-strand break (DSB) repair. FANCJ also functions
      in interstrand crosslinks (ICLs) repair by linking to mismatch repair protein
      complex MLH1-PMS2 (MutLalpha). While oxaliplatin causes ICLs, 5FU is considered
      to cause DSBs. Therefore, we investigated the importance of FANCJ in the
      synergistic effects of oxaliplatin and 5FU in MKN45 gastric cancer cells and the
      derived 5FU-resistant cell line, MKN45/F2R. METHODS: MKN1, TMK1, MKN45, and
      MKN45/F2R (5FU-resistant) gastric cancer cells were treated with 5FU and/or
      oxaliplatin. The signaling pathway was evaluated by a western blotting analysis
      and reverse transcription polymerase chain reaction (RT-PCR). Drug resistance was
      evaluated by the 3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium
      bromide (MTT) assay. RESULTS: In MKN45 cells, the combination of 5FU and
      oxaliplatin had synergistic effects. DSBs appeared when the cells were treated
      with 5FU. FANCJ was down-regulated, and BRCA1 was induced in a dose- and time
      dependent manner. MKN45 cells showed increased sensitivity to oxaliplatin when
      FANCJ was knocked down by short interfering (si) RNA. However, these findings
      were not observed in MKN45/F2R 5FU-resistant cells. CONCLUSION: These results
      strongly suggest that the decrease in FANCJ caused by 5FU treatment leads to an
      increase in sensitivity to oxaliplatin, thus indicating that the FANCJ protein
      plays an important role in the synergism of the combination of 5FU and
      oxaliplatin.

PMID- 22968821
TI  - The silent epidemic of reproductive morbidity among ever married women (15-49
      years) in an urban area of Delhi.
AB  - Concept of reproductive health has long been discussed and need to focus on
      reproductive morbidity as a measure of reproductive health has evolved. There is
      poor reproductive health with neglect of women's own health. Compounded with
      socio-cultural factors, the result is poor treatment seeking and hence poor
      quality of life. This community based study was conducted to find out the
      magnitude, type of reproductive morbidity and treatment seeking behavior for the
      same. Cross sectional study was conducted in Palam Village among married women
      aged 15-49 years. 750 women were interviewed by visiting every fifth house
      through systematic random sampling. Symptomatic women were referred for
      gynecological examination and investigations. The overall prevalence of
      Reproductive Morbidity was found to be 46.3 %: Gynaecological morbidity in 31.3 %
      subjects, obstetric morbidity in 43.4 % of the eligible women and contraceptive
      induced morbidity in 11.2 % of the ever contraceptive users with 5 % reporting
      more than one symptom. Problem perception and treatment compliance was poor for
      subjects with gynecological morbidity as compared with contraceptive and
      obstetric morbidity respectively. High self-reported obstetric morbidity was
      observed with good treatment seeking behavior as compared to poor treatment
      seeking behavior in women with gynaecological morbidity. Contraceptive morbidity
      was reported by fewer subjects but treatment seeking was good. There is a need to
      understand the pattern of reporting and health seeking behavior among women
      suffering from reproductive morbidity. The large magnitude of reproductive
      morbidity warrants attention and hints the poor quality of MCH care delivered to
      women.

PMID- 22968819
TI  - Molecular, cellular, and structural mechanisms of cocaine addiction: a key role
      for microRNAs.
AB  - The rewarding properties of cocaine play a key role in establishing and
      maintaining the drug-taking habit. However, as exposure to cocaine increases,
      drug use can transition from controlled to compulsive. Importantly, very little
      is known about the neurobiological mechanisms that control this switch in drug
      use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA
      transcripts that can regulate the expression of messenger RNAs that code for
      proteins. Because of their highly pleiotropic nature, each miRNA has the
      potential to regulate hundreds or even thousands of protein-coding RNA
      transcripts. This property of miRNAs has generated considerable interest in their
      potential involvement in complex psychiatric disorders such as addiction, as each
      miRNA could potentially influence the many different molecular and cellular
      adaptations that arise in response to drug use that are hypothesized to drive the
      emergence of addiction. Here, we review recent evidence supporting a key role for
      miRNAs in the ventral striatum in regulating the rewarding and reinforcing
      properties of cocaine in animals with limited exposure to the drug. Moreover, we
      discuss evidence suggesting that miRNAs in the dorsal striatum control the
      escalation of drug intake in rats with extended cocaine access. These findings
      highlight the central role for miRNAs in drug-induced neuroplasticity in brain
      reward systems that drive the emergence of compulsive-like drug use in animals,
      and suggest that a better understanding of how miRNAs control drug intake will
      provide new insights into the neurobiology of drug addiction.

PMID- 22968822
TI  - Ohio Appalachia public health department personnel: human papillomavirus (HPV)
      vaccine availability, and acceptance and concerns among parents of male and
      female adolescents.
AB  - Public health departments (n = 48) serving the 32 counties of Ohio Appalachia
      were contacted to determine human papillomavirus (HPV) vaccine availability and
      to assess patient and parental attitudes, perceived barriers, and decisional
      differences about vaccination for male and female adolescents. Nurses or nursing
      supervisors in 46 of 48 health departments agreed to participate with 45 (97.8 %)
      reporting that HPV vaccines were available for males and females. HPV vaccination
      barriers reported most frequently were lack of knowledge about the vaccines,
      concerns about potential side effects, the newness of the HPV vaccines, and
      parents believing their children were not sexually active or were too young to
      receive an HPV vaccine. Provider reports of the primary differences in the
      acceptability of an HPV vaccine among parents of males compared to the parents of
      females were lack of awareness that an HPV vaccine was available for males, not
      understanding why the vaccine should be given to males, and fear of vaccination
      increasing sexual promiscuity among female adolescents. Half of the health
      departments (n = 24) reported that parents of females were more receptive toward
      HPV vaccination, 16 health departments reported no difference in acceptability
      based on gender of the child, and 5 health departments reported that parents of
      males were more receptive. This study suggests that there are different
      informational needs of males and females and parents of male and female children
      when making an informed decision about HPV vaccination. Findings highlight
      content to include in strategies to increase HPV vaccination rates among
      Appalachia Ohio residents.

PMID- 22968823
TI  - Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy
      using subconjunctival triamcinolone injections.
AB  - BACKGROUND: To evaluate the efficacy of subconjunctival triamcinolone injection
      for treating upper eyelid retraction caused by thyroid-associated ophthalmopathy
      (TAO). METHODS: Prospective single blind randomized clinical trial. Patients
      diagnosed with TAO-associated eyelid retraction and/or swelling <6 months before
      study onset were randomly assigned to triamcinolone-injected (group I; 55
      patients, 75 eyes) or observation-only (group II; 40 patients, 59 eyes)
      populations. Group I received 1-3 injections of 20 mg triamcinolone acetate into
      the subconjunctival eyelid, between the conjunctiva and Muller's muscle, at 3
      week intervals. Group I was followed up at 3, 6, 9, and 24 weeks post-injection,
      and group II was evaluated at 9 and 24 weeks after initial visit. Eyelid swelling
      and retraction were each graded on a 0-3 scale. Treatment was stopped after 1-2
      injections if both swelling and retraction resolved completely or if retraction
      and swelling scored 0/1 or 1/0 without functional or cosmetic patient concerns.
      Treatment success was defined at 9 and 24 weeks post-injection if eyelids were
      normal or when treatment was terminated because of early clinical resolution. We
      compared baseline clinical data between success and failure group evaluated at 9
      and 24 weeks in group I, and investigated short-term and long-term success
      prognostic factor using multiple logistic regression analysis in each group I and
      II. RESULTS: Swelling and retraction decreased significantly more in group I than
      in group II. Significantly more eyes had severe swelling (>= grade 2) in group I
      (67 %) than in group II (34 %) upon initial evaluation (p < 0.01); this
      difference disappeared at 9 and 24 weeks. Fewer severely retracted eyes were
      observed in group I than in group II at 9 and 24 weeks (p < 0.01). Significantly
      more eyes in group I achieved success at both 9 and 24 weeks (59 %, 75 %) than in
      group II (39 %, 57 %) (p = 0.03, p = 0.04 respectively). Higher initial
      retraction grades (2-3) predicted a higher chance of post-injection failure
      versus the reference group (grade 0-1) at 9 and 24 weeks in group I, with
      adjusted odds ratios (aOR) 45.4 (95 % CI = 5.9-351.1, p < 0.01) and aOR 11.6 (95
      % CI = 2.3-58.5, p < 0.01) respectively. Similarly in group II, initial
      retraction grade was associated with the failure at 9 and 24 weeks, with aOR 10.3
      (95 % CI = 1.8-59.6, p < 0.01) and aOR 5.9 (95 % CI = 1.3-25.9, p < 0.05)
      respectively. Transient intraocular pressure elevation was observed in three eyes
      of two patients, although all ocular pressures were normalized within 1 month
      using anti-glaucoma medication. CONCLUSIONS: Subconjunctival triamcinolone
      injections were very effective in resolving eyelid swelling and retraction in
      recent-onset TAO. However, the symptom-reducing effect of triamcinolone was
      modest and less effective in patients initially presenting with severe retraction
      grades. As intraocular pressure may rise after steroid injection at upper eyelid,
      the treatment should be avoided in patients suspected to have glaucoma.

PMID- 22968825
TI  - Mouse genomics programs and resources.

PMID- 22968824
TI  - The mammalian gene function resource: the International Knockout Mouse
      Consortium.
AB  - In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious
      promise to generate mutations in virtually every protein-coding gene of the mouse
      genome in a concerted worldwide action. Now, 5 years later, the IKMC members have
      developed high-throughput gene trapping and, in particular, gene-targeting
      pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell
      clones and more than 1,700 mutant mouse strains, most of them conditional. A
      common IKMC web portal (www.knockoutmouse.org) has been established, allowing
      easy access to this unparalleled biological resource. The IKMC materials
      considerably enhance functional gene annotation of the mammalian genome and will
      have a major impact on future biomedical research.

PMID- 22968826
TI  - High knee valgus in female subjects does not yield higher knee translations
      during drop landings: a biplane fluoroscopic study.
AB  - The goal of this study was to determine the effects of peak knee valgus angle and
      peak knee abductor moment on the anterior, medial, and lateral tibial
      translations (ATT, MTT, LTT) in the "at risk" female knee during drop landing.
      Fifteen female subjects performed drop landings from 40 cm. Three-dimension knee
      motion was simultaneously recorded using a high speed, biplane fluoroscopy
      system, and a video-based motion analysis system. Valgus knee angles and knee
      abduction moments were stratified into low, intermediate, and high groups and
      peak ATT, MTT, and LTT were compared between these groups with ANOVA (alpha =
      0.05). Significant differences were observed between stratified groups in peak
      knee valgus angle (p < 0.0001) and peak knee abduction moment (p < 0.0001).
      However, no corresponding differences in peak ATT, LTT, and MTT between groups
      exhibiting low to high-peak knee valgus angles (ATT: p = 0.80; LTT: p = 0.25;
      MTT: p = 0.72); or, in peak ATT (p = 0.61), LTT (p = 0.26) and MTT (p = 0.96)
      translations when stratified according to low to high knee abduction moments,
      were found. We conclude that the healthy female knee is tightly regulated with
      regard to translations even when motion analysis derived knee valgus angles and
      abduction moments are high.

PMID- 22968827
TI  - Differentially expressed proteins identified in overexpressed let-7a gastric
      carcinoma cells by two-dimensional polyacrylamide gel electrophoresis.
AB  - MicroRNAs are small noncoding RNA molecules that control the expression of target
      genes. Our previous studies show that let-7a decreased in gastric carcinoma and
      that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma
      cell growth both in vitro and in vivo, whereas it remains largely unclear as to
      how let-7a affects tumor growth. In this study, proteins associated with the
      function of let-7a were detected in high-throughput screening. The cell line of
      SGC-7901 stably overexpressing let-7a was successfully established by gene clone.
      Two-dimensional gel electrophoresis (2-DE) was used to separate the total
      proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was
      applied to analyze 2-DE images. Ten differential protein spots were identified by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and
      they may be the proteins associated with let-7a function. The overexpressed
      proteins include antioxidant protein 2, insulin-like growth factor binding
      protein 2, protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, cyclin
      dependent kinase inhibitor1 (CDKN1) and Rho-GTPase activating protein 4. The
      underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2),
      platelet membrane glycoprotein, fibronectin and Cks1 protein. Furthermore, the
      different expression levels of the partial proteins (CDKN1,Spk2 and Fibronectin)
      were confirmed by Western blot analysis. The data suggest that these differential
      proteins are involved in novel let-7a signal pathway, and these findings provided
      the basis to comprehensively investigate the functional mechanisms of let-7a in
      gastric carcinoma.

PMID- 22968828
TI  - Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered
      metabolite profiles and growth retardation without an accumulation of oxidative
      damage.
AB  - Lon1 is an ATP-dependent protease and chaperone located in the mitochondrial
      matrix in plants. Knockout in Arabidopsis (Arabidopsis thaliana) leads to a
      significant growth rate deficit in both roots and shoots and lowered activity of
      specific mitochondrial enzymes associated with respiratory metabolism. Analysis
      of the mitochondrial proteomes of two lon1 mutant alleles (lon1-1 and lon1-2)
      with different severities of phenotypes shows a common accumulation of several
      stress marker chaperones and lowered abundance of Complexes I, IV, and V of
      OXPHOS. Certain enzymes of the tricarboxylic acid (TCA) cycle are modified or
      accumulated, and TCA cycle bypasses were repressed rather than induced. While
      whole tissue respiratory rates were unaltered in roots and shoots, TCA cycle
      intermediate organic acids were depleted in leaf extracts in the day in lon1-1
      and in both lon mutants at night. No significant evidence of broad steady-state
      oxidative damage to isolated mitochondrial samples could be found, but peptides
      from several specific proteins were more oxidized and selected functions were
      more debilitated in lon1-1. Collectively, the evidence suggests that loss of Lon1
      significantly modifies respiratory function and plant performance by small but
      broad alterations in the mitochondrial proteome gained by subtly changing steady
      state protein assembly, stability, and damage of a range of components that
      debilitate an anaplerotic role for mitochondria in cellular carbon metabolism.

PMID- 22968829
TI  - Rhamnolipids elicit defense responses and induce disease resistance against
      biotrophic, hemibiotrophic, and necrotrophic pathogens that require different
      signaling pathways in Arabidopsis and highlight a central role for salicylic
      acid.
AB  - Plant resistance to phytopathogenic microorganisms mainly relies on the
      activation of an innate immune response usually launched after recognition by the
      plant cells of microbe-associated molecular patterns. The plant hormones,
      salicylic acid (SA), jasmonic acid, and ethylene have emerged as key players in
      the signaling networks involved in plant immunity. Rhamnolipids (RLs) are
      glycolipids produced by bacteria and are involved in surface motility and biofilm
      development. Here we report that RLs trigger an immune response in Arabidopsis
      (Arabidopsis thaliana) characterized by signaling molecules accumulation and
      defense gene activation. This immune response participates to resistance against
      the hemibiotrophic bacterium Pseudomonas syringae pv tomato, the biotrophic
      oomycete Hyaloperonospora arabidopsidis, and the necrotrophic fungus Botrytis
      cinerea. We show that RL-mediated resistance involves different signaling
      pathways that depend on the type of pathogen. Ethylene is involved in RL-induced
      resistance to H. arabidopsidis and to P. syringae pv tomato whereas jasmonic acid
      is essential for the resistance to B. cinerea. SA participates to the restriction
      of all pathogens. We also show evidence that SA-dependent plant defenses are
      potentiated by RLs following challenge by B. cinerea or P. syringae pv tomato.
      These results highlight a central role for SA in RL-mediated resistance. In
      addition to the activation of plant defense responses, antimicrobial properties
      of RLs are thought to participate in the protection against the fungus and the
      oomycete. Our data highlight the intricate mechanisms involved in plant
      protection triggered by a new type of molecule that can be perceived by plant
      cells and that can also act directly onto pathogens.

PMID- 22968830
TI  - Strigolactones are involved in root response to low phosphate conditions in
      Arabidopsis.
AB  - Strigolactones (SLs) are plant hormones that suppress lateral shoot branching,
      and act to regulate root hair elongation and lateral root formation. Here, we
      show that SLs are regulators of plant perception of or response to low inorganic
      phosphate (Pi) conditions. This regulation is mediated by MORE AXILLARY GROWTH2
      (MAX2) and correlated with transcriptional induction of the auxin receptor
      TRANSPORT INHIBITOR RESPONSE1 (TIR1). Mutants of SL signaling (max2-1) or
      biosynthesis (max4-1) showed reduced response to low Pi conditions relative to
      the wild type. In max4-1, but not max2-1, the reduction in response to low Pi was
      compensated by the application of a synthetic strigolactone GR24. Moreover,
      AbamineSG, which decreases SL levels in plants, reduced the response to low Pi in
      the wild type, but not in SL-signaling or biosynthesis mutants. In accordance
      with the reduced response of max2-1 to low Pi relative to the wild type, several
      phosphate-starvation response and phosphate-transporter genes displayed reduced
      induction in max2-1, even though Pi content in max2-1 and the wild type were
      similar. Auxin, but not ethylene, was sufficient to compensate for the reduced
      max2-1 response to low Pi conditions. Moreover, the expression level of TIR1 was
      induced under low Pi conditions in the wild type, but not in max2-1. Accordingly,
      the tir1-1 mutant showed a transient reduction in root hair density in comparison
      with the wild type under low Pi conditions. Therefore, we suggest that the
      response of plants to low Pi is regulated by SLs; this regulation is transmitted
      via the MAX2 component of SL signaling and is correlated with transcriptional
      induction of the TIR1 auxin receptor.

PMID- 22968831
TI  - Genomics and localization of the Arabidopsis DHHC-cysteine-rich domain S
      acyltransferase protein family.
AB  - Protein lipid modification of cysteine residues, referred to as S-palmitoylation
      or S-acylation, is an important secondary and reversible modification that
      regulates membrane association, trafficking, and function of target proteins.
      This enzymatic reaction is mediated by protein S-acyl transferases (PATs). Here,
      the phylogeny, genomic organization, protein topology, expression, and
      localization pattern of the 24 PAT family members from Arabidopsis (Arabidopsis
      thaliana) is described. Most PATs are expressed at ubiquitous levels and tissues
      throughout the development, while few genes are expressed especially during
      flower development preferentially in pollen and stamen. The proteins display
      large sequence and structural variations but exhibit a common protein topology
      that is preserved in PATs from various organisms. Arabidopsis PAT proteins
      display a complex targeting pattern and were detected at the endoplasmic
      reticulum, Golgi, endosomal compartments, and the vacuolar membrane. However,
      most proteins were targeted to the plasma membrane. This large concentration of
      plant PAT activity to the plasma membrane suggests that the plant cellular S
      acylation machinery is functionally different compared with that of yeast
      (Saccharomyces cerevisiae) and mammalians.

PMID- 22968832
TI  - Laparoscopic greater curve plication in Asia: initial experience.
AB  - BACKGROUND: This study aimed to evaluate the effectiveness and safety of
      laparoscopic greater curve plication (LGCP) for the treatment of obesity in
      ethnic Chinese in Hong Kong. METHODS: Twenty-seven consecutive Chinese patients
      (23 females; mean age 37.6 +/- 8.9 years) received LGCP for the treatment of
      obesity from September 2010 to December 2011. Mean baseline body weight (BW) and
      body mass index (BMI) were 84.6 +/- 17.5 kg and 31.2 +/- 4.7 kg/m(2),
      respectively. RESULTS: All procedures were performed laparoscopically with
      conversion to open surgery in one patient. There was neither mortality nor any
      postoperative complications. Mean follow-up was 10.6 +/- 6.5 months. Mean
      procedure time was 117.9 +/- 22.3 min and mean hospital stay was 2.6 +/- 0.7
      days. Mean BMI loss was 4.1 +/- 1.6, 4.8 +/- 2.0 and 5.2 +/- 2.5 kg/m(2) at 3, 6
      and 12 months. Mean % EBL was 67.3 +/- 42.1, 66.4 +/- 35.9 and 60.2 +/- 25.5 % at
      3, 6 and 12 months. Mean % EBL in BMI >35 group (n = 7) was 38.2 +/- 11.1, 43.5
      +/- 14.0 and 50.6 +/- 21.6 % at 3, 6 and 12 months. Mean % EBL in BMI <35 group
      (n = 20) was 76.5 +/- 44.2, 76.5 +/- 38.2 and 65.0 +/- 27.0 % at 3, 6 and 12
      months. CONCLUSIONS: LGCP is safe and effective in achieving significant weight
      loss in obese ethnic Chinese patients. However, weight loss in BMI <35 is more
      pronounced. It is a very valid alternative to other procedures in Asian
      population.

PMID- 22968834
TI  - Neurospora as a model to empirically test central hypotheses in eukaryotic genome
      evolution: why this fungal genus offers promising opportunities.
AB  - The fungus Neurospora comprises a novel model for testing hypotheses involving
      the role of sex and reproduction in eukaryotic genome evolution. Its variation in
      reproductive mode, lack of sex-specific genotypes, availability of phylogenetic
      species, and young sex-regulating chromosomes make research in this genus
      complementary to animal and plant models.

PMID- 22968833
TI  - Barbed versus usual suture for closure of the gastrojejunal anastomosis in
      laparoscopic gastric bypass: a comparative trial.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass is one of the main bariatric
      procedures that require safe and reproducible anastomosis. The objective of this
      study is to compare the risk of leaks and stenosis of a mechanical gastric pouch
      jejunal anastomosis between the usual interrupted sutures and a continuous barbed
      suture for gastrojejunotomy, in order to reduce procedure time and costs.
      METHODS: A comparative trial of 100 consecutive patients undergoing laparoscopic
      Roux-en-Y gastric bypass was performed between October 2010 and July 2011. The
      population was divided into two groups of 50 consecutive patients. In the first
      group, gastrojejunotomy was sutured with resorbable interrupted sutures and the
      second with continuous barbed suture. Diabetes, body mass index and the American
      Society of Anaesthesiology score were compared. The time required for suturing
      and the incidence of anastomotic leaks and stricture were also compared after 6
      months. RESULTS: No fistulas or anastomotic stenoses had occurred at post
      operative month 6 in either group. Gastrojejunotomy suture time was significantly
      shorter in the barbed suture group (11 versus 8.22 min; p < 0.01). Total costs of
      material to complete the reconstruction were significantly lower in the barbed
      suture group (?26.69 versus ?18.33; p < 0.001). CONCLUSIONS: The use of barbed
      suture is as safe as usual sutures and allows easier and faster suture in the
      closure of gastrojejunotomy. This suture could be incorporated in the standard
      laparoscopic Roux-en-Y gastric bypass technique.

PMID- 22968836
TI  - A novel composite porous coating approach for bioactive titanium-based orthopedic
      implants.
AB  - Surface modification of titanium-based implants is considered a highly effective
      solution to enhance osseointegration. This study describes a novel
      Ti/hydroxyapatite (HA) composite porous coating produced using a cold spraying
      technique. Experimental results indicate desirable open-cell structure with 50
      150 MUm pore size and 60-65% macroporosity. In particular, the reinforced HA
      particles are exposed to the surface of the coating resulting in enhanced
      mineralization ability in simulated body fluid. None of the coatings displayed a
      cytotoxic response in SaOS-2 cells cultured in vitro for up to 48 h. The bond
      strength between the porous coating and the Ti substrate was found to be 20 MPa.
      These properties are comparative to or better than products currently on the
      market and thus this novel coating has potential use in orthopedics.

PMID- 22968835
TI  - Stem cells for reprogramming: could hUMSCs be a better choice?
AB  - Human umbilical cord mesenchymal stem cells (hUMSC) are primitive multipotent
      cells capable of differentiating into cells of different lineages. They can be an
      alternative source of pluripotent cells since they are ethically and regulatory
      approved, are easily obtained and have low immunogenicity compared to embryonic
      stem cells which are dogged with numerous controversies. hUMSC can be a great
      source for cell and transplantation therapy.

PMID- 22968837
TI  - Does acupuncture activate endogenous analgesia in chronic whiplash-associated
      disorders? A randomized crossover trial.
AB  - BACKGROUND: Many patients with chronic pain, including those with chronic
      whiplash-associated disorders (WAD), show features of central sensitization.
      Randomized trials examining whether treatments are able to influence the process
      of central sensitization in patients with chronic WAD are emerging. Therefore,
      the present study aimed at examining whether acupuncture results in activation of
      endogenous analgesia and relief in symptoms in patients with chronic WAD.
      METHODS: In this randomized crossover pilot trial with blinded assessors, each
      patient (n = 39) received two treatment sessions of identical duration, with
      acupuncture and relaxation therapy randomly crossed over in visit 2. Primary
      outcome measurement included immediate activation of endogenous analgesia i.e.,
      pressure pain sensitivity and conditioned pain modulation. Secondary outcome
      measurements included pain relief and reduced disability level. RESULTS: Local
      pressure pain sensitivity at baseline and during conditioned pain modulation
      decreased significantly more following acupuncture compared with relaxation (time
      * group interactions: p < 0.001), both in the neck and at a site distinct from
      the painful region. When comparing the effects of acupuncture versus relaxation,
      no differences were observed on conditioned pain modulation, temporal summation
      of pressure pain, neck disability or symptom severity (all p-values >0.05).
      CONCLUSION: It was shown that one session of acupuncture treatment results in
      acute improvements in pressure pain sensitivity in the neck and calf of patients
      with chronic WAD. Acupuncture had no effect on conditioned pain modulation or
      temporal summation of pressure pain. Both acupuncture and relaxation appear to be
      well-tolerated treatments for people with chronic WAD. These findings suggest
      that acupuncture treatment activates endogenous analgesia in patients with
      chronic WAD.

PMID- 22968838
TI  - All-inorganic colloidal quantum dot photovoltaics employing solution-phase halide
      passivation.
AB  - A new solution-phase halide passivation strategy to improve the electronic
      properties of colloidal quantum dot films is reported. We prove experimentally
      that the approach leads to an order-of-magnitude increase in mobility and a
      notable reduction in trap state density. We build solar cells having the highest
      efficiency (6.6%) reported using all-inorganic colloidal quantum dots. The
      improved photocurrent results from increased efficiency of collection of infrared
      generated photocarriers.

PMID- 22968840
TI  - Synthesis and crystal structure of two synthetic oxofluoride framework compounds-
      Co2TeO3F2 and Co2SeO3F2.
AB  - Two new isostructural Co(2+) containing tellurium and selenium oxofluoride
      compounds Co(2)TeO(3)F(2) and Co(2)SeO(3)F(2) are synthesized and their
      structures determined by single crystal X-ray diffraction. They crystallize in
      the orthorhombic space group Pnma with the unit cell parameters a = 7.3810(5) A,
      b = 10.1936(7) A, c = 5.3013(3) A and a = 7.2655(8) A, b = 10.0013(13) A, c =
      5.3564(6) A, respectively. The Co(II) ion has octahedral coordination
      [CoO(3)F(3)] and builds up a 3D framework by corner- and edge sharing. The Se(IV)
      and the Te(IV) ions have the coordinations [SeO(3)E] and [TeO(3)E] respectively
      where E is the lone-pair electrons. The Se(IV) and Te(IV) ions are isolated from
      each other and bond only to the [CoO(3)F(3)] polyhedra. The electronegative
      element fluorine takes the role of a network builder like oxygen and helps to
      form the 3D framework structure. This is a difference compared to many oxohalide
      compounds containing Cl and Br where the halide ions are terminating ions
      preventing a 3D network from being formed. Long range antiferromagnetic
      interactions dominate at temperatures < 20 K. The magnetic susceptibility follows
      the Curie-Weiss law above 25 K with the Curie constant C = 5.62 emu K mol(-1),
      the Weiss temperature theta = -56 K and the effective magnetic moment MU(eff) =
      4.74 MU(B) per cobalt atom.

PMID- 22968839
TI  - Efficient assembly of iminodicarboxamides by a "truly" four-component reaction.

PMID- 22968841
TI  - Chick embryo culture and electroporation.
AB  - Important events in embryonic development such as gastrulation, neurulation, and
      cranial neural crest development occur in ectodermal tissues during vertebrate
      embryonic development. Although the chicken embryo is a well-established model
      system in developmental biology, problems of accessibility of the ectoderm for
      experimental manipulation and an inability to generate gene knockouts previously
      impeded studies of gene regulation and key processes during chicken gastrulation
      and neurulation. The technique of in ovo electroporation permits genetic
      manipulation and provides a powerful animal model. However, the problem of
      accessibility to the ectoderm in ovo requires an ex ovo whole-embryo culture
      approach combined with electroporation. This unit provides convenient and
      reproducible whole-embryo ex ovo culture and electroporation protocols. These
      chicken embryo culture protocols can be used not only for gene regulatory
      experiments, but also for time-lapse imaging of the dynamics of early vertebrate
      development.

PMID- 22968842
TI  - Analysis of interactions between genomic loci through Chromosome Conformation
      Capture (3C).
AB  - Genome architecture plays a significant role in the regulation of DNA-based
      cellular processes such as transcription and recombination. The successful
      accomplishment of these processes involves coordinated interaction of DNA
      elements located at a distance from each other. The 'Chromosome Conformation
      Capture' (3C) assay is a convenient tool for identification of physical
      association between spatially separated DNA elements in a cell under
      physiological conditions. The principle of 3C is to convert physical chromosomal
      interactions into specific DNA ligation products, which are then detected by PCR.
      The 3C protocol was originally used to identify long-range, stable chromosomal
      interactions in yeast. Here we describe a modified 3C procedure that can detect
      transient, short-range interactions of DNA elements separated by a distance of
      less than 700 bp. This method has been successfully used to detect dynamic
      interaction of transcription regulatory elements in yeast and can be used for
      detecting similar interactions of other genomic regions.

PMID- 22968843
TI  - Assays to measure nuclear mechanics in interphase cells.
AB  - The nucleus is the characteristic hallmark of all eukaryotic cells. The physical
      properties of the nucleus reflect important biological characteristics, such as
      chromatin organization or nuclear envelope composition; they can also directly
      affect cellular function, e.g., when cells pass through narrow constrictions,
      where the stiff nucleus may present a limiting factor. We present two
      complementary techniques to probe the mechanical properties of the nucleus. In
      the first, nuclear stiffness relative to the surrounding cytoskeleton is inferred
      from induced nuclear deformations during strain application to cells on an
      elastic substrate. In the second approach, nuclear deformability is deduced from
      the transit time through a perfusion-based microfabricated device with
      constrictions smaller than the size of the nucleus. These complementary methods,
      which can be applied to measure nuclear stiffness in large numbers of living
      adherent or suspended cells, can help identify important changes in nuclear
      mechanics associated with disease or development.

PMID- 22968844
TI  - Metabolic labeling with noncanonical amino acids and visualization by
      chemoselective fluorescent tagging.
AB  - Fluorescent labeling of proteins by genetically encoded fluorescent protein tags
      has enabled an enhanced understanding of cell biological processes but is
      restricted to the analysis of a limited number of identified proteins. This
      approach does not permit, e.g., the unbiased visualization of a full proteome in
      situ. We describe here a fluorescence-based method to follow proteome-wide
      patterns of newly synthesized proteins in cultured cells, tissue slices, and a
      whole organism. This technique is compatible with immunohistochemistry and in
      situ hybridization. Key to this method is the introduction of a small bio
      orthogonal reactive group by metabolic labeling. This is accomplished by
      replacing the amino acid methionine by the azide-bearing methionine surrogate
      azidohomoalanine (AHA) in a step very similar to classical radioisotope labeling.
      Subsequently, an alkyne-bearing fluorophore is covalently attached to the group
      by "click chemistry"--a copper(I)-catalyzed [3+2]azide-alkyne cycloaddition. By
      similar means, metabolic labeling can also be performed with the alkyne-bearing
      homopropargylglycine (HPG) and clicked to an azide-functionalized fluorophore.

PMID- 22968845
TI  - Unexpected luminescence properties of Sr(0.25)Ba(0.75)Si2O2N2:Eu(2+)--a narrow
      blue emitting oxonitridosilicate with cation ordering.
AB  - Owing to a parity allowed 4f(6)((7)F)5d(1)->4f(7)((8)S(7/2)) transition, powders
      of the nominal composition Sr(0.25)Ba(0.75)Si(2)O(2)N(2):Eu(2+) (2 mol% Eu(2+))
      show surprising intense blue emission (lambda(em)=472 nm) when excited by UV to
      blue radiation. Similarly to other phases in the system Sr(1
      x)Ba(x)Si(2)O(2)N(2):Eu(2+), the described compound is a promising phosphor
      material for pc-LED applications as well. The FWHM of the emission band is 37 nm,
      representing the smallest value found for blue emitting (oxo)nitridosilicates so
      far. A combination of electron and X-ray diffraction methods was used to
      determine the crystal structure of Sr(0.25)Ba(0.75)Si(2)O(2)N(2):Eu(2+). HRTEM
      images reveal the intergrowth of nanodomains with SrSi(2)O(2)N(2) and
      BaSi(2)O(2)N(2)-type structures, which leads to pronounced diffuse scattering.
      Taking into account the intergrowth, the structure of the BaSi(2)O(2)N(2)-type
      domains was refined on single-crystal diffraction data. In contrast to coplanar
      metal atom layers which are located between layers of condensed SiON(3)
      tetrahedra in pure BaSi(2)O(2)N(2), in Sr(0.25)Ba(0.75)Si(2)O(2)N(2):Eu(2+)
      corrugated metal atom layers occur. HRTEM image simulations indicate cation
      ordering in the final structure model, which, in combination with the corrugated
      metal atom layers, explains the unexpected and excellent luminescence properties.

PMID- 22968846
TI  - Lead vegetations in patients with local and systemic cardiac device infections:
      prevalence, risk factors, and therapeutic effects.
AB  - AIMS: Actual rates of lead vegetations (LVs) in cardiovascular device infections
      (CDI) are debated in this study. The aim of this study is to characterize
      prevalence and risk factors of LV in patients with CDI treated with lead
      extraction (LE). METHODS AND RESULTS: Between 2003 and 2011, 293 leads were
      extracted from 136 patients (age 70.5 +/- 14.5 years, 109 male) with infective
      indications: 39.2% chronic draining sinus, 20.9% pocket infections, and 28.8%
      systemic infections/sepsis. All patients underwent transesophageal
      echocardiography (TEE) before LE. Lead vegetation prevalence was 40.4%: 62.2% in
      systemic infection, but noteworthy in local infection/chronic draining sinus
      (21.9/36.4%). Younger age, renal disease, ad dialysis were associated with
      systemic infection. Fever after last intervention, revision, previous reparative
      procedure, infection at wound/device site and infection >6 months were associated
      with local infection/chronic draining sinus. Cardiac resynchronization therapy
      device, fever after last intervention, infection <6 months, renal disease,
      dialysis, abnormal chest X-ray, fever at admission, pulmonary symptoms, white
      blood cell (WBC) count, erythrocyte sedimentation rate, C-reactive protein
      increase and positive blood samples were related to LV. Risk of vegetations was
      reduced by antibiotic prophylaxis. Multivariate analysis indicated that renal
      failure and increased WBC count were related to LV. CONCLUSION: Lead vegetations
      were frequently observed in patients with only local symptoms. Therefore, TEE
      should be mandatory in all patients undergoing LE for infective indications.

PMID- 22968847
TI  - Antitachycardia pacing to terminate ventricular tachyarrhythmia: new insights
      into how to reduce painful implantable cardioverter defibrillator shocks.

PMID- 22968848
TI  - Lack of current implantable cardioverter defibrillator guidelines application for
      primary prevention of sudden cardiac death in Latin American patients with heart
      failure: a cross-sectional study.
AB  - AIMS: This cross-sectional study evaluated the application of accepted
      international implantable cardioverter defibrillator (ICD) guidelines for primary
      prevention of sudden cardiac death in patients with heart failure. METHODS AND
      RESULTS: The PLASMA (Probabilidad de Sufrir Muerte Arritmica) study was designed
      to characterize management of cardiac patients in Latin America. Twelve centres
      included 1958 consecutively admitted patients in cardiology units in 2008 and
      2009. Discharged patients were evaluated for primary prevention, ICD indication
      and prescription by general cardiologists. Of 1711 discharged patients, 1525
      (89%) had data available for evaluating indication status. Class I indications
      for ICD therapy were met for 153 (10%) patients based on collected data. Only 20
      (13%, 95% confidence interval: 7.7-18.4%) patients with indication were
      prescribed an ICD. Patients prescribed an ICD were younger than patients who were
      not prescribed an ICD (62 vs. 68 years, P < 0.01). The reasons given by
      cardiologists for not prescribing an ICD for 133 patients with an indication
      were: indication criteria not met (75%), life expectancy <1 year (9.7%),
      rejection by the patient (5.2%), no medical coverage paying for the device
      (3.7%), psychiatric patient (2.2%), and other reasons (4.2%). CONCLUSIONS: In
      Latin America, international guidelines for primary prevention ICD implantation
      are not well followed. The main reason is that cardiologists believe that
      patients do not meet indication criteria, even though study data confirm that
      criteria are met. This poses a significant challenge and underlines the
      importance of continuous and improved medical education.

PMID- 22968849
TI  - The implantable defibrillator and return to operation of vehicles study.
AB  - AIMS: We sought to characterise driving habits of contemporary implantable
      cardioverter defibrillator (ICD) patients. METHODS AND RESULTS: We performed a
      multicentre prospective observational study of consecutive ICD recipients. Non
      commercial drivers with a valid licence were eligible. Patient and ICD data were
      recorded. All patients completed an anonymous questionnaire regarding their
      driving habits. Among 275 patients, 25 (9.1%) stopped driving permanently after
      ICD implantation. During a mean follow-up of 26.5 +/- 4.5 months, 25.3% of
      patients received an ICD shock (52.5% appropriate). The median time to first
      shock was 7.0 (2.5, 17.5) months and was not significantly different between
      primary and secondary ICD patients. However, shocks (36.5 vs. 21.3%, P = 0.027)
      and recurrent shock episodes (17.5 vs. 6.2%, P = 0.011) were more common in
      secondary ICD patients. Physician-recommended driving restrictions were not
      recalled by 37.9% and not followed by 23.0% of patients. Overall, the mean
      duration of driving abstinence was 2.2 +/- 2.9 and 3.6 +/- 5.3 months for primary
      and secondary patients, respectively. Notably, 36.5% of secondary patients drove
      within 1 month. Eight patients (3.3%) received a shock while driving, five of
      which resulted in road traffic accidents. The annual risk of a shock while
      driving was 1.5%. CONCLUSIONS: Patient driving behaviour following ICD
      implantation is variable, with over one-third not remembering and almost one
      quarter not adhering to physician-directed driving restrictions. Over one-third
      of secondary ICD patients drive within 1 month despite physician recommendations.
      Further studies are required to establish the optimal duration of driving
      restriction in ICD recipients.

PMID- 22968850
TI  - Effects of insulin on altered mechanical and electrical papillary muscle
      activities of diabetic rats.
AB  - Since insulin compounds can restore some metabolic parameters and lipid profile
      alterations of the diabetic rat heart, we investigated whether these beneficial
      effects extend to diabetic rat cardiac dysfunctions. Twenty-four male Wistar
      albino rats, 6 months of age with an average body weight of 250-320 g, were
      divided randomly into three groups, each consisting of eight rats: control-group
      (C) rats were fed with standard rat nutrient and water; diabetic-group (D) rats
      were treated with a single intramuscular injection of streptozotocin (STZ, 45
      mg/kg), dissolved in 0.01 M sodium citrate, pH adjusted to 4.5; and insulin
      treated diabetic group (D + INS) rats were treated with subcutaneous injections
      of 1 IU/l insulin (INS) twice a day after a single intramuscular injection of STZ
      (45 mg/kg). Treatment of D rats with INS caused a time-dependent decrease in
      blood glucose. We found that the lipid profile and HbA(1c) levels in the D + INS
      group reached the values of control rats at the end of the treatment period.
      Contraction force in group D was compared with values from groups C and D + INS
      (p < 0.05). Values were obtained at a muscle contraction and relaxation time of
      milliseconds, with contraction time in D compared to C and D compared to D + INS
      and C (p < 0.05). Rate-dependent changes in action potential configuration in
      left ventricular papillary muscle obtained from 8-week control, STZ-treated D and
      D + INS rats showed significant membrane potential changes between C and STZ
      treated D animals. Action potential amplitude showed significant changes between
      matched D + INS and STZ-treated D animals. Depolarization time showed significant
      changes between C and STZ-treated D animals and between the D + INS and D groups.
      Half-repolarization time showed significant changes between D + INS and STZ
      treated D animals and compared to the D and C groups. Our data suggest that the
      beneficial effects of insulin treatment on the mechanical and electrical
      activities of the diabetic rat heart appear to be due to restoration of the
      diminished K+ currents, partially related to the restoration of hyperglycemia.

PMID- 22968851
TI  - Left circumflex coronary artery is protected against no-reflow phenomenon
      following percutaneous coronary intervention for coronary artery disease.
AB  - Despite the positive impact of percutaneous coronary intervention (PCI) on
      reducing mortality, a small percentage of patients experience poor myocardial
      reperfusion following PCI. However, factors associated with no-reflow remain
      unclear. We investigated clinical factors associated with no-reflow following PCI
      for coronary artery disease (CAD). We retrospectively analyzed 1622 consecutive
      CAD patients who underwent PCI over a 5-year period at our institution. Patients
      were divided into two groups according to the presence (n = 31) or absence (n =
      1591) of no-reflow, defined as Thrombolysis in Myocardial Infarction flow grade
      <3 after PCI. No significant differences in patient characteristics or PCI
      strategy were seen between the no-reflow and normal flow groups. The incidence of
      no-reflow was significantly lower in the left circumflex artery (LCx) than in the
      left anterior descending artery (LAD) (P = 0.0015), with no differences in
      characteristics or PCI strategy between these two target vessels. Multivariate
      analysis revealed that involvement of the LCx was an independent protective
      factor against no-reflow (odds ratio 0.14, 95 % confidence interval 0.02-0.98, P
      = 0.044). In conclusion, LCx as the target vessel was protective against no
      reflow compared with LAD following PCI for CAD. Our results suggest that embolic
      protection devices may be unnecessary in CAD patients with involvement of LCx. 

PMID- 22968852
TI  - Oral sarpogrelate can improve endothelial dysfunction as effectively as oral
      cilostazol, with fewer headaches, in active young male smokers.
AB  - Sarpogrelate and cilostazol are two commonly used adjunctive antiplatelet agents
      that also can be used to improve endothelial dysfunction. We compared the effects
      of sarpogrelate and cilostazol on endothelial dysfunction in active male smokers
      with flow-mediated dilatation (FMD). We enrolled and compared baseline and follow
      up FMD in 20 young male smokers without any known cardiovascular diseases. Two
      participants who were initially medicated with cilostazol dropped out because of
      severe headache after taking medication. However, they continued the other
      experiment with sarpogrelate medication. Baseline endothelium-dependent
      dilatation (EDD) after reactive hyperemia was 7.5 % +/- 1.9 % and endothelium
      independent dilatation (EID) after sublingual administration of nitroglycerin was
      13.3 % +/- 3.4 %. After a 2-week treatment of cilostazol, follow-up EDD
      significantly increased (7.7 % +/- 1.9 to 8.8 +/- 2.0 %, P = 0.016), but follow
      up EID changed insignificantly (13.2 % +/- 3.5 to 12.5 % +/- 3.9 %, P = 0.350).
      With the sarpogrelate treatment, follow-up EDD was significantly increased (7.4 %
      +/- 1.9 % to 8.8 % +/- 1.9 %, P = 0.021), but follow-up EID was similar (13.5 %
      +/- 3.5 to 14.0 % +/- 3.2 %, P = 0.427). There was no clinical significance
      between the two groups on follow-up EDD and EID (P = 0.984 and 0.212,
      respectively). However, the mean score of intensity of headache was significantly
      higher in the cilostazol group than in the sarpogrelate group (3.8 % +/- 2.5 % vs
      1.4 % +/- 2.2 %, P = 0.005). EDD showed a similar significant increase with 2
      week treatment of cilostazol and sarpogrelate. However, intensity of headaches
      was significantly higher in the cilostazol group. 

PMID- 22968853
TI  - Ultrasound analysis of the relationship between right internal jugular vein and
      common carotid artery in the left head-rotation and head-flexion position.
AB  - Common carotid artery (CCA) injury is a serious complication of internal jugular
      vein (IJV) cannulation. To minimize unintentional CCA puncture, the anatomic
      relationship between the IJV and the CCA and the size of IJV were compared under
      different head positions. Ultrasound analyses of the IJV and the CCA were
      performed in 103 consecutive patients. Overlapping angle (OA), real puncture
      angle (RPA) and diameter of IJV (D IJV) were evaluated with 30 degrees  and 60
      degrees  left rotation and with 30 degrees  left flexion. When the head position
      was changed from 30 degrees  left rotation to 60 degrees  left rotation, OA
      increased significantly from 6.5 degrees  +/- 7.7 degrees  to 14.5 degrees  +/-
      7.4 degrees  at the cricoid cartilage level (Cricoid-level) and from 14.4 degrees
      +/- 8.4 degrees  to 20.6 degrees  +/- 6.9 degrees  at the middle triangle level
      (Triangle-level), whereas RPA decreased significantly at these levels (from 49.7
      degrees  +/- 11.9 degrees  to 43.5 degrees  +/- 13.1 degrees  and from 51.1
      degrees  +/- 14.4 degrees  to 44.3 degrees  +/- 13.9 degrees , respectively; P <
      0.01 for both). When the head position was changed from 30 degrees  left rotation
      to 30 degrees  left flexion, neither OA nor RPA significantly changed (OA: 6.3
      degrees  +/- 6.1 degrees  and 15.0 degrees  +/- 7.2 degrees , RPA: 48.5 degrees 
      +/- 12.4 degrees  and 51.8 degrees  +/- 13.6 degrees , P not significant vs 30
      degrees  left rotation). There was no difference in D IJV when comparing 30
      degrees  left rotation and 30 degrees  left flexion, although D IJV was largest
      at 60 degrees  left rotation. RPA positively correlated with age, and D IJV
      positively correlated with body mass index. In conclusion, excessive left
      rotation should be avoided to minimize the probability of unintentional CCA
      puncture during IJV cannulation. When 30 degrees  left rotation is not feasible,
      the head-flexion position should be utilized.

PMID- 22968854
TI  - Bioavailability of intravenous fosphenytoin sodium in healthy Japanese
      volunteers.
AB  - To compare and evaluate the bioavailability for intravenous fosphenytoin sodium
      with that of intravenous phenytoin sodium in Japanese subjects. In study 1,
      healthy Japanese male volunteers received a 30-min infusion of 375 mg
      fosphenytoin sodium or an equimolar dose of 250 mg phenytoin by a double-blind,
      crossover method. In study 2, other healthy Japanese male volunteers received a
      30-min or 10-min infusion of 563 mg fosphenytoin sodium, followed by a dose of
      750 mg after 2 weeks in an unblinded manner. Comparing with 250 mg phenytoin
      sodium, 375 mg fosphenytoin sodium exhibited lower total plasma phenytoin C max,
      whereas the geometric mean ratio of the AUC of total and free phenyotoin for
      fosphenytoin sodium at a dose of 375 mg was very similar to phenytoin sodium at a
      equimolar dose of 250 mg (AUC0-t ratio: 0.98 and 1.02, respectively). Therefore,
      fosphenytoin is almost completely converted to phenytoin in subjects.
      Fosphenytoin sodium was rapidly converted to phenytoin at doses of 375, 563, and
      750 mg. The maximum concentration (C max) of total plasma phenytoin increased in
      a dose-dependent manner. The area under the plasma concentration-time curve (AUC)
      increased slightly more than proportionally with the administered dose, and
      clearance (CL) decreased with increasing dose. Pain and other infusion-site
      reactions were reported by all 12 subjects with phenytoin sodium, whereas very
      few symptoms were observed with fosphenytoin sodium. In conclusion, fosphenytoin
      sodium is considered to be a useful substitute for phenytoin sodium with almost
      no associated injection-site reactions.

PMID- 22968855
TI  - Diagnosis and treatment of multiple myeloma and AL amyloidosis with focus on
      improvement of renal lesion.
AB  - Multiple myeloma (MM) and AL amyloidosis are caused by the expansion of
      monoclonal plasma cells and secretion of dysproteinemia (Bence Jones protein and
      free light chain) and some patients require the hemodialysis. Myeloma kidney is
      mainly caused by the cast nephropathy of the distal tubuli, whereas, AL amyloid
      protein is mainly deposited in glomeruli with massive fibrillar involvement.
      Therefore, almost MM patients presents a symptom of renal insufficiency, whereas,
      almost patients of AL amyloidosis present a nephrotic syndrome with severe
      hypoalbuminemia. These two diseases have some similar characteristics such as up
      regulation of cyclin D1 gene by 11:14 chromosomal translocation. High-dose
      chemotherapy supported with autologous peripheral blood stem cells is effective
      for these two diseases. However, they are still difficult to be cured and require
      long-term disease control. In recent years, introduction of novel agents has
      changed their treatment strategies from the palliation therapy to the clinical
      cure.

PMID- 22968856
TI  - Decreased expression of aquaporin 2 in the collecting duct of mice lacking the
      vasopressin V1a receptor.
AB  - BACKGROUND: Vasopressin V1a receptor null (V1aR(-/-)) mice recently showed
      incomplete urinary concentration due to higher urine volume during control and
      water diuresis (euhydration), but showed normal response during dehydration
      (Aoyagi et al., Am J Physiol 295: F100-7, 2008). METHODS: Water balance, plasma
      vasopressin, plasma and urine osmolality, and aquaporin 2 (AQP2) expression in
      the kidney of wild-type (WT) and V1aR(-/-) mice were therefore further examined
      using improved methods of urine collection (urinary bladder urine). RESULTS:
      V1aR(-/-) mice demonstrated a lower urine osmolality (3,360 +/- 138 vs. 3,610 +/-
      47 mOsm/kgH2O) and a higher plasma osmolality (354.3 +/- 1.3 vs. 342.5 +/- 1.5
      mOsm/kgH2O) after dehydration for 24 h compared to WT mice (P < 0.05). In
      contrast, the plasma vasopressin concentration was significantly (P < 0.001)
      higher in the V1aR(-/-) mice (48.8 +/- 4.8 vs. 22.1 +/- 2.4 pg/ml). On the other
      hand, although the AQP2 protein expression in the kidney was increased after
      dehydration, the basal (control) and dehydration-induced AQP2 protein levels were
      significantly lower in V1aR(-/-) mice compared to WT mice (by Western blotting).
      Staining by an anti-AQP2 antibody in the luminal membrane of the collecting ducts
      was increased in both V1aR(-/-) and WT mice after dehydration, but was relatively
      weaker in the V1aR(-/-) mice (by immunohistochemistry). Moreover, urinary
      excretion of AQP2 protein, an index of the luminal AQP2 expression, was
      significantly (P < 0.05) lower in the V1aR(-/-) mice. CONCLUSION: V1aR signaling
      may be fundamentally important for the expression of AQP2 in the collecting ducts
      during control conditions and dehydration.

PMID- 22968857
TI  - ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma.
AB  - Chondrosarcoma is a unique type of bone cancer in that it does not respond to
      chemotherapy or radiation therapy, and therefore many affected patients die from
      metastatic disease. Metastasis has been correlated with the upregulation of the
      matrix metalloproteinase (MMP) family of proteases, which can degrade
      extracellular components. ETV5 is a transcription factor which has shown to be
      overexpressed in various types of invasive tumors. We hypothesized that ETV5
      regulates MMP2 in human chondrosarcoma with the protease acting as a downstream
      effector. Gene knock-down of ETV5 in human chondrosarcoma cells reduces MMP2 mRNA
      expression as well as decreased protein production and significantly decreased
      MMP2 activity. With plasmid transfected ETV5 upregulation, MMP2 expression is
      similarly upregulated at the gene expression and protein levels. Data from our
      bone resorption studies revealed that when a matrix metalloproteinase-2 inhibitor
      is added to the growth media of chondrosarcoma cells, collagen released from bone
      chips incubated with the cells decreased by 27%. This data suggests that ETV5 has
      a significant role in regulating MMP2 expression and therefore matrix resorption
      in human chondrosarcoma, and thus may be a targetable upstream effector of the
      metastatic cascade in this cancer.

PMID- 22968858
TI  - N-Acetyl-seryl-aspartyl-lysyl-proline inhibits ET-1-induced collagen production
      by preserving Src homology 2-containing protein tyrosine phosphatase-2 activity
      in cardiac fibroblasts.
AB  - N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits endothelin-1 (ET-1)
      induced activation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) and
      collagen production in cultured rat cardiac fibroblasts (RCFs). However, we do
      not know whether its inhibitory effect on p44/42 MAPK is due to the altered
      activity of protein tyrosine phosphatases (PTPs), which in turn downregulate the
      p44/42 MAPK signaling pathway. The activity of Src homology 2-containing protein
      tyrosine phosphatase-2 (SHP-2) is downregulated by ET-1 in RCFs; thus, we
      hypothesized that Ac-SDKP inhibits ET-1-stimulated collagen production in part by
      preserving SHP-2 activity and thereby inhibiting p44/42 MAPK phosphorylation.
      When we stimulated RCFs with ET-1 in the presence or absence of Ac-SDKP, we found
      that (a) PTP activity was reduced by ET-1 and (b) this effect was counteracted by
      Ac-SDKP in a dose-dependent fashion. Next, we extracted SHP-2 from RCF lysates by
      immunoprecipitation and determined that (a) ET-1 inhibited SHP-2 by 40 % and (b)
      this effect was prevented by Ac-SDKP. However, Ac-SDKP failed to inhibit ET-1
      induced p44/42 MAPK phosphorylation in RCFs treated with SHP-2 short hairpin RNA
      (shRNA); in contrast, in cells transfected with control shRNA, Ac-SDKP's
      inhibitory effect on ET-1-induced p44/42 MAPK activation remained intact.
      Moreover, the inhibitory effect of Ac-SDKP on ET-1-stimulated collagen production
      was blunted in cells treated with the SHP-1/2 inhibitor NSC-87877. Thus, we
      concluded that the inhibitory effect of Ac-SDKP on ET-1-stimulated collagen
      production by RCFs is mediated in part by preserving SHP-2 activity and thereby
      preventing p44/42 MAPK activation. Ac-SDKP or its analogs could represent a new
      therapeutic tool to treat fibrotic diseases in the cardiovascular system.

PMID- 22968859
TI  - Single molecule magnetism in a MU-phenolato dinuclear lanthanide motif ligated by
      heptadentate Schiff base ligands.
AB  - The heptadentate Schiff base ligand, 2-(2-hydroxyphenyl)-1,3-bis[4-(2
      hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazoline (H(3)api), yields [Ln(2)api(2)]
      species when combined with lanthanide salts under basic conditions. A survey of
      the magnetic properties of this dinuclear lanthanide motif (Ln = Gd, Tb, Dy, Ho)
      has identified weak magnetic exchange, antiferromagnetic in nature for the
      isotropic gadolinium analogue, while single molecule magnetic behaviour is
      displayed in the case of the anisotropic dysprosium complex.

PMID- 22968860
TI  - Commissioning advocate resigns after becoming disillusioned with what GPs are
      being asked to do.

PMID- 22968861
TI  - Asian and Afro-Caribbean Britons have double the risk of type 2 diabetes.

PMID- 22968862
TI  - Heat related deaths could rise from 2000 to 12 000 a year by the 2080s, health
      agency says.

PMID- 22968863
TI  - Children's champion says more needs to be done for children whose parents misuse
      alcohol.

PMID- 22968864
TI  - FDA proposes tightening post-market oversight of medical devices.

PMID- 22968867
TI  - The cover. Old cloth series.

PMID- 22968870
TI  - Lessons from Massachusetts: cost remains a hurdle for those with public
      insurance.

PMID- 22968871
TI  - Caution urged in ramping up use of transcatheter aortic valve replacement.

PMID- 22968872
TI  - Children's deaths linked with postsurgical codeine.

PMID- 22968877
TI  - Prenatal micronutrient and early pregnancy food supplementation in Bangladesh.

PMID- 22968879
TI  - PEPFAR and adult mortality.

PMID- 22968881
TI  - Changes in direct-to-consumer pharmaceutical advertising following shifts from
      prescription-only to over-the-counter status.

PMID- 22968883
TI  - The attending physician on the wards: finding a new homeostasis.

PMID- 22968884
TI  - Engaging physicians and leveraging professionalism: a key to success for quality
      measurement and improvement.

PMID- 22968885
TI  - Surgical vs lifestyle treatment for type 2 diabetes.

PMID- 22968886
TI  - Changing eating habits for the medical profession.

PMID- 22968887
TI  - Piece of my mind. A path to wholeness.

PMID- 22968889
TI  - Association between sentinel lymph node excision with or without preoperative
      SPECT/CT and metastatic node detection and disease-free survival in melanoma.
AB  - CONTEXT: Malignant melanoma has become an increasing interdisciplinary public
      health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the
      most sensitive and specific staging test for the detection of micrometastatic
      melanoma in regional lymph nodes. OBJECTIVE: To compare metastatic node detection
      and disease-free survival using single-photon emission computed
      tomography/computed tomography (SPECT/CT)-aided SLNE vs standard SLNE in patients
      with melanoma. DESIGN, SETTING, AND PATIENTS: A prospective, computerized
      melanoma patient database at the University Hospital Essen, Skin Cancer Center,
      Essen, Germany, was used to identify a cohort of 464 patients eligible for SLNE
      between March 2003 and April 2011. A total of 403 patients with clinically
      negative lymph nodes, who underwent SLNE with or without preoperative SPECT/CT,
      qualified for subsequent analysis. MAIN OUTCOME MEASURES: Metastatic node
      detection and disease-free survival. RESULTS: Between March 2003 and October
      2008, 254 patients underwent the standard SLNE technique. After November 2008,
      149 patients underwent the SPECT/CT technique. Patients who did not receive SNLE
      in both intervals (46/300 [15.34%] for standard cohort vs 15/164 [9.15%] for
      SPECT/CT cohort; P = .06) did not differ in either age (difference, 69.20 years;
      95% CI, 62.84-72.07 years; P = .38), tumor depth (difference, 2.90 mm; 95% CI,
      2.87-4.54 mm; P = .54), or ulceration of the primary tumor (difference, -8.00%;
      95% CI, -35.74% to 19.81%; P = .59). However, using SPECT/CT allowed SLNE in the
      head and neck area more frequently (2.0% for standard vs 23.5% for SPECT/CT;
      difference, 21.1%; 95% CI, 14.1%-28.2%; P < .001). In the SPECT/CT cohort, more
      sentinel lymph nodes per patient were detected than in the standard cohort (2.40
      vs 1.87; 95% CI, 1.93-2.18; P < .001). The number of positive sentinel lymph
      nodes per patient was significantly higher in the SPECT/CT cohort than in the
      standard cohort (0.34 vs 0.21; 95% CI, 0.21-0.31; P = .04). The local relapse
      rate in the SPECT/CT cohort was lower than in the standard cohort (6.8% vs 23.8%,
      P = .03), which prolonged 4-year disease-free survival (93.9% vs 79.2%; P = .02).
      CONCLUSION: Among patients with clinically lymph node-negative melanoma, the use
      of SPECT/CT-aided SLNE compared with SLNE alone was associated with a higher
      frequency of metastatic involvement and a higher rate of disease-free survival.

PMID- 22968888
TI  - Comparison of physician-, biomarker-, and symptom-based strategies for adjustment
      of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized
      controlled trial.
AB  - CONTEXT: No consensus exists for adjusting inhaled corticosteroid therapy in
      patients with asthma. Approaches include adjustment at outpatient visits guided
      by physician assessment of asthma control (symptoms, rescue therapy, pulmonary
      function), based on exhaled nitric oxide, or on a day-to-day basis guided by
      symptoms. OBJECTIVE: To determine if adjustment of inhaled corticosteroid therapy
      based on exhaled nitric oxide or day-to-day symptoms is superior to guideline
      informed, physician assessment-based adjustment in preventing treatment failure
      in adults with mild to moderate asthma. DESIGN, SETTING, AND PARTICIPANTS: A
      randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342
      adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid
      therapy (n = 114 assigned to physician assessment-based adjustment [101
      completed], n = 115 to biomarker-based [exhaled nitric oxide] adjustment [92
      completed], and n = 113 to symptom-based adjustment [97 completed]), the Best
      Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by
      the Asthma Clinical Research Network at 10 academic medical centers in the United
      States for 9 months between June 2007 and July 2010. INTERVENTIONS: For physician
      assessment-based adjustment and biomarker-based (exhaled nitric oxide)
      adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for
      symptom-based adjustment, inhaled corticosteroids were taken with each albuterol
      rescue use. MAIN OUTCOME MEASURE: The primary outcome was time to treatment
      failure. RESULTS: There were no significant differences in time to treatment
      failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24
      events) for physician assessment-based adjustment, 20% (97.5% CI, 13%-30%; 21
      events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for
      symptom-based adjustment. The hazard ratio for physician assessment-based
      adjustment vs biomarker-based adjustment was 1.2 (97.5% CI, 0.6-2.3). The hazard
      ratio for physician assessment-based adjustment vs symptom-based adjustment was
      1.6 (97.5% CI, 0.8-3.3). CONCLUSION: Among adults with mild to moderate
      persistent asthma controlled with low-dose inhaled corticosteroid therapy, the
      use of either biomarker-based or symptom-based adjustment of inhaled
      corticosteroids was not superior to physician assessment-based adjustment of
      inhaled corticosteroids in time to treatment failure. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00495157.

PMID- 22968890
TI  - Spending differences associated with the Medicare Physician Group Practice
      Demonstration.
AB  - CONTEXT: The Centers for Medicare & Medicaid Services (CMS) recently launched
      accountable care organization (ACO) programs designed to improve quality and slow
      cost growth. The ACOs resemble an earlier pilot, the Medicare Physician Group
      Practice Demonstration (PGPD), in which participating physician groups received
      bonus payments if they achieved lower cost growth than local controls and met
      quality targets. Although evidence indicates the PGPD improved quality,
      uncertainty remains about its effect on costs. OBJECTIVE: To estimate cost
      savings associated with the PGPD overall and for beneficiaries dually eligible
      for Medicare and Medicaid. DESIGN: Quasi-experimental analyses comparing
      preintervention (2001-2004) and postintervention (2005-2009) trends in spending
      of PGPD participants to local control groups. We compared estimates using several
      alternative approaches to adjust for case mix. SETTING: Ten physician groups from
      across the United States. PATIENTS AND PARTICIPANTS: The intervention group was
      composed of fee-for-service Medicare beneficiaries (n = 990,177) receiving care
      primarily from the physicians in the participating medical groups. Controls were
      Medicare beneficiaries (n = 7,514,453) from the same regions who received care
      largely from non-PGPD physicians. Overall, 15% of beneficiaries were dually
      eligible for Medicare and Medicaid. MAIN OUTCOME MEASURE: Annual spending per
      Medicare fee-for-service beneficiary. RESULTS: Annual savings per beneficiary
      were modest overall (adjusted mean $114, 95% CI, $12-$216). Annual savings were
      significant in dually eligible beneficiaries (adjusted mean $532, 95% CI, $277
      $786), but were not significant among nondually eligible beneficiaries (adjusted
      mean $59, 95% CI, $166 in savings to $47 in additional spending). The adjusted
      mean spending reductions were concentrated in acute care (overall, $118, 95% CI,
      $65-$170; dually eligible: $381, 95% CI, $247-$515; nondually eligible: $85, 95%
      CI, $32-$138). There was significant variation in savings across practice groups,
      ranging from an overall mean per-capita annual saving of $866 (95% CI, $815-$918)
      to an increase in expenditures of $749 (95% CI, $698-$799). Thirty-day medical
      readmissions decreased overall (-0.67%, 95% CI, -1.11% to -0.23%) and in the
      dually eligible (-1.07%, 95% CI, -1.73% to -0.41%), while surgical readmissions
      decreased only for the dually eligible (-2.21%, 95% CI, -3.07% to -1.34%).
      Estimates were sensitive to the risk-adjustment method. CONCLUSIONS: Substantial
      PGPD savings achieved by some participating institutions were offset by a lack of
      saving at other participating institutions. Most of the savings were concentrated
      among dually eligible beneficiaries.

PMID- 22968891
TI  - Association between omega-3 fatty acid supplementation and risk of major
      cardiovascular disease events: a systematic review and meta-analysis.
AB  - CONTEXT: Considerable controversy exists regarding the association of omega-3
      polyunsaturated fatty acids (PUFAs) and major cardiovascular end points.
      OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular
      outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of
      Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical
      trials evaluating the effect of omega-3 on all-cause mortality, cardiac death,
      sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and
      quantitative information was extracted; absolute and relative risk (RR) estimates
      were synthesized under a random-effects model. Heterogeneity was assessed using
      the Q statistic and I2. Subgroup analyses were performed for the presence of
      blinding, the prevention settings, and patients with implantable cardioverter
      defibrillators, and meta-regression analyses were performed for the omega-3 dose.
      A statistical significance threshold of .0063 was assumed after adjustment for
      multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies
      of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths,
      1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No
      statistically significant association was observed with all-cause mortality (RR,
      0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02),
      cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00),
      sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to
      0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95%
      CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95%
      CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION:
      Overall, omega-3 PUFA supplementation was not associated with a lower risk of all
      cause mortality, cardiac death, sudden death, myocardial infarction, or stroke
      based on relative and absolute measures of association.

PMID- 22968892
TI  - Short fourth and fifth metacarpals.

PMID- 22968893
TI  - Inhaled corticosteroid dose adjustment in mild persistent asthma.

PMID- 22968894
TI  - ACOs--promise, not panacea.

PMID- 22968895
TI  - Challenges to excellence in child health research: call for papers.

PMID- 22968898
TI  - The surgical safety checklist survey: a national perspective on patient safety.
AB  - BACKGROUND: In 2008, the World Health Organisation (WHO) recommended practices to
      ensure the safety of patients worldwide. This led to the development of the
      Surgical Safety Checklist (SSC). Ireland has endorsed the SSC ( www.hiqa.ie/press
      release/2008-06-17-health-information-and-quality-authority-launches-world-health
      organization , 10). OBJECTIVES: We aimed to determine (i) whether SSC is being
      implemented, (ii) whether it promotes a safer surgical environment and (iii)
      identify problems associated with its introduction and on-going implementation.
      METHODS: All hospitals in Ireland with operating departments (n = 61) were
      invited to participate in an online survey. RESULTS: The response rate was 67 %.
      The WHO SSC or modified version is in place in 78 % (mean time: 20 months) of
      operating departments that responded. Partaking in Time Out as a team was
      reported as occurring in 57 % of cases. Greater than 60 % of respondents reported
      that the SSC was difficult to introduce and implement and that its introduction
      was time consuming. Further training in using the SSC was reported as desirable
      by 84 % of respondents. The introduction of the SSC was reported to be associated
      with an improvement in team communication (72 %), a positive change in team
      behaviour (63 %), an increase in the consistency of patient care (82 %) and a
      positive culture of safety in theatre (81 %). CONCLUSION: The SSC has not been
      implemented throughout all operating departments in Ireland. Where it has been
      introduced there has been a perceived positive change in safety culture. However,
      overall greater education, endorsement, teamwork, and communication will be
      required to optimise the potential benefits associated with this safety
      instrument. In order to properly determine the benefit of the SSC following its
      implementation, a formal audit of morbidity and mortality is required.

PMID- 22968899
TI  - Neocellularization and neovascularization of nanosized bioactive glass-coated
      decellularized trabecular bone scaffolds.
AB  - In this study, the in vivo recellularization and neovascularization of nanosized
      bioactive glass (n-BG)-coated decellularized trabecular bone scaffolds were
      studied in a rat model and quantified using stereological analyses. Based on the
      highest amount of vascular endothelial growth factor (VEGF) secreted by human
      fibroblasts grown on n-BG coatings (0-1.245 mg/cm(2)), decellularized trabecular
      bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG
      particles at a coating density of 0.263 mg/cm(2), human fibroblasts produced 4.3
      times more VEGF than on uncoated controls. After 8 weeks of implantation in
      Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated
      with newly formed tissue (47-48%) and blood vessels (3-4%). No significant
      differences were found in cellularization and vascularization between uncoated
      bone scaffolds and n-BG-coated scaffolds. This finding indicates that the
      decellularized bone itself may exhibit growth-promoting properties induced by the
      highly interconnected pore microarchitecture and/or proteins left behind on
      decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG
      coated bone scaffolds, a bioactive coating is considered to be beneficial to
      impart osteoinductive and osteoconductive properties to decellularized bone. n-BG
      coated bone grafts have thus high clinical potential for the regeneration of
      complex tissue defects given their ability for recellularization and
      neovascularization.

PMID- 22968900
TI  - Enhanced catalytic activity of self-assembled-monolayer-capped gold
      nanoparticles.
AB  - An unprecedented substrate-selective catalytic enhancement effect of an
      alkanethiol-self-assembled monolayer (SAM) on Au nanoparticles (AuNPs) is
      reported. In the supported 2D-array of AuNPs, the alkanethiol-SAM acts as a
      protein-like soft reaction space in which the substrate molecules are
      encapsulated through non-covalent intermolecular hydrophobic interactions, and
      thus catalytic reactions are accelerated at AuNP surfaces.

PMID- 22968902
TI  - Dinuclear palladium complexes--precursors or catalysts?
AB  - Calculations help: Recent work from Schoenebeck's group has demonstrated beyond
      reasonable doubt that the dimeric LPd(I) Br catalysts that are widely used in
      coupling chemistry operate through prior formal reduction to an LPd(0) species.
      Conversely, L(2)Pd(0) catalysts can be activated by oxidation. In other cases a
      binuclear species can persist through the catalytic cycle.

PMID- 22968901
TI  - Silyl ketene imines: highly versatile nucleophiles for catalytic, asymmetric
      synthesis.
AB  - This Minireview provides an overview on the development of silyl ketene imines
      and their recent applications in catalytic, enantioselective reactions. The
      unique structure of the ketene imine allows a diverse range of reactivity
      patterns and provides solutions to existing challenges in the enantioselective
      construction of quaternary stereogenic carbon centers and cross-benzoin adducts.
      A variety of reactions for which silyl ketene imines have been applied are
      presented with an overall goal of inspiring new uses for these underutilized
      nucleophiles.

PMID- 22968903
TI  - Novel complex phenomena in ferroelectric nanocomposites.
AB  - A first-principles-based effective Hamiltonian is used to investigate finite
      temperature properties of ferroelectric nanocomposites made of periodic arrays of
      ferroelectric nanowires embedded in a matrix formed by another ferroelectric
      material. Novel transitions and features related to flux-closure configurations
      are found. Examples include (i) a vortex core transition, that is characterized
      by the change of the vortex cores from being axisymmetric to exhibiting a 'broken
      symmetry'; (ii) translational mode of the vortex cores; (iii) striking zigzag
      dipolar chains along the vortex core axis; and (iv) phase-locking of
      ferroelectric vortices accompanied by ferroelectric antivortices. These complex
      phenomena are all found to coexist with a spontaneous electrical polarization
      aligned along the normal of the plane containing the vortices.

PMID- 22968904
TI  - Highly sensitive and fast-responsive fluorescent chemosensor for palladium:
      reversible sensing and visible recovery.
AB  - The well-known rhodamine spiro-lactam framework offers an ideal model for the
      development of fluorescence-enhanced chemosensors through simple and convenient
      syntheses. Herein, we report a new tridentate PNO receptor, which was introduced
      into a rhodamine spiro-lactam system to develop Pd(2+)-chemosensor RPd4, that
      displayed significantly improved sensing properties for palladium. Compound RPd4
      shows a very fast response time (about 5 s), high sensitivity (5 nM), and
      excellent specificity for Pd(2+) ions over other PGE ions (Pt(2+), Rh(3+), and
      Ru(3+)). In addition, RPd4 displays quite different responses to different
      valence states of the Pd ions, that is, very fast response towards Pd(2+) ions
      but slow response towards Pd(0), which may provide us with a convenient method
      for the selective discrimination of Pd species in different valence states.
      According to proof-of-concept experiments, RPd4 has potential applications in
      Pd(2+)-analysis in drug compounds, water, soil, and leaf samples. Owing to its
      good reversibility, RPd4 can also be used as a sensor material for the selective
      detection and visual recovery of trace Pd(2+) ions in environmental samples.

PMID- 22968905
TI  - The eIF4E repressor protein 4E-BP2 is merely truncated, despite 4E-BP1
      degradation in the porcine uterine tissue during implantation.
AB  - Recently, we identified an N-terminally truncated form of the mRNA cap binding
      protein eIF4E in the porcine luminal epithelium during implantation. EIF4E
      truncation is accompanied by degradation of the eIF4E-repressor protein 4E-BP1.
      In this study, we investigated whether or not the other members of the eIF4E
      repressor family, namely 4E-BP2 and 4E-BP3, were also modified during early
      pregnancy. We did not detect 4E-BP3 in the uterine tissue; however, 4E-BP2
      emerged in one or two stable fragments on pregnancy day 15. 4E-BP2 truncation
      most likely occurs at the N-terminus, and this calcium-stimulated processing
      depends on progesterone and estradiol. The activities targeting eIF4E, 4E-BP1,
      and 4E-BP2 were found in different fractions after anionic exchange
      chromatography, indicating the action of different proteases. Detailed protein
      interaction studies with immobilized anti-eIF4E and m(7) GTP-Sepharose showed a
      differential binding of the 4E-BP2 isoforms to the eIF4E variants and to the cap
      structure. In general, truncation of eIF4E reduces the inhibitory impact of 4E
      BP2, whereas truncation of 4E-BP2 restores repression by binding the prototype
      eIF4E. In this context, we suggest long-term translational repression by the
      truncated 4E-BP2 is affected by the loss of the RAIP motif located at the N
      terminus, which is indispensable for phosphorylation and deactivation of the
      molecule. In conclusion, we propose a tightly balanced regulation of the
      truncation of the cap-binding complex component eIF4F and degradation of 4E-BP1
      and/or truncation of 4E-BP2 that together ensures correct translational control
      during the dynamic process of conceptus implantation.

PMID- 22968906
TI  - Targeting hedgehog-GLI-2 pathway in osteosarcoma.
AB  - Osteosarcoma is the most common primary malignant tumor of bone. Patients with
      localized osteosarcoma are routinely treated with chemotherapy and surgery.
      However, many of these patients eventually relapse after these treatments. In
      such cases, there are limited treatment options for these patients and most will
      eventually die with metastatic disease. Therefore, it is imperative to identify
      better therapeutic strategies. Hedgehog-GLI is responsible for the development of
      vertebrate embryonic and tumorigenesis. Specifically, the transcription factor,
      GLI-2, plays a key role in development of normal prostate. Aberrant activation of
      GLI-2 is correlated with various malignancies. We observe that GLI-2 is highly
      expressed in osteosarcoma cell lines, and this correlates with poor clinical
      outcomes in patients. Knockdown of GLI-2 by siRNA decreases osteosarcoma cell
      proliferation and viability, which eventually induces cell death as revealed in
      both in 2D and 3D cultures. In addition, we notice that administration of GLI-2
      siRNA can increase the sensitivity of osteosarcoma cells to chemotherapeutic
      drugs. These findings suggest GLI-2 is required for osteosarcoma cell
      proliferation and survival. GLI-2 may be exploited as a therapeutic target for
      the treatment of osteosarcoma patients.

PMID- 22968907
TI  - Formation and dissociation of phosphorylated peptide radical cations.
AB  - In this study, we generated phosphoserine- and phosphothreonine-containing
      peptide radical cations through low-energy collision-induced dissociation (CID)
      of the ternary metal-ligand phosphorylated peptide complexes
      [Cu(II)(terpy)(p)M](.2+) and [Co(III)(salen)(p)M](.+) [(p)M: phosphorylated
      angiotensin III derivative; terpy: 2,2':6',2''-terpyridine; salen: N,N'
      ethylenebis(salicylideneiminato)]. Subsequent CID of the phosphorylated peptide
      radical cations ((p)M(.+)) revealed fascinating gas-phase radical chemistry,
      yielding (1) charge-directed b- and y-type product ions, (2) radical-driven
      product ions through cleavages of peptide backbones and side chains, and (3)
      different degrees of formation of [M - H(3)PO(4)](.+) species through phosphate
      ester bond cleavage. The CID spectra of the (p)M(.+) species and their non
      phosphorylated analogues featured fragment ions of similar sequence, suggesting
      that the phosphoryl group did not play a significant role in the fragmentation of
      the peptide backbone or side chain. The extent of neutral H(3)PO(4) loss was
      influenced by the peptide sequence and the initial sites of the charge and
      radical. A preliminary density functional theory study, at the B3LYP 6
      311++G(d,p) level of theory, of the neutral loss of H(3)PO(4) from a prototypical
      model--N-acetylphosphorylserine methylamide--revealed several factors governing
      the elimination of neutral phosphoryl groups through charge- and radical-induced
      mechanisms.

PMID- 22968908
TI  - Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at
      the lateral semi-circular canal.
AB  - Perilymph pharmacokinetics was investigated by a novel approach, in which
      solutions containing drug or marker were injected from a pipette sealed into the
      perilymphatic space of the lateral semi-circular canal (LSCC). The cochlear
      aqueduct provides the outlet for fluid flow so this procedure allows almost the
      entire perilymph to be exchanged. After wait times of up to 4 h the injection
      pipette was removed and multiple, sequential samples of perilymph were collected
      from the LSCC. Fluid efflux at this site results from cerebrospinal fluid (CSF)
      entry into the basal turn of scala tympani (ST) so the samples allow drug levels
      from different locations in the ear to be defined. This method allows the rate of
      elimination of substances from the inner ear to be determined more reliably than
      with other delivery methods in which drug may only be applied to part of the ear.
      Results were compared for the markers trimethylphenylammonium (TMPA) and
      fluorescein and for the drug dexamethasone (Dex). For each substance, the
      concentration in fluid samples showed a progressive decrease as the delay time
      between injection and sampling was increased. This is consistent with the
      elimination of substance from the ear with time. The decline with time was
      slowest for fluorescein, was fastest for Dex, with TMPA at an intermediate rate.
      Simulations of the experiments showed that elimination occurred more rapidly from
      scala tympani (ST) than from scala vestibuli (SV). Calculated elimination half
      times from ST averaged 54.1, 24.5 and 22.5 min for fluorescein, TMPA and Dex
      respectively and from SV 1730, 229 and 111 min respectively. The elimination of
      Dex from ST occurred considerably faster than previously appreciated. These
      pharmacokinetic parameters provide an important foundation for understanding of
      drug treatments of the inner ear.

PMID- 22968909
TI  - Anti-microbial peptide (AMP): nucleotide variation, gene expression, and host
      resistance in the white pine blister rust (WPBR) pathosystem.
AB  - Pinus monticola antimicrobial peptide (PmAMP1) inhibits growth of Cronartium
      ribicola and other fungal pathogens. C. ribicola causes white pine blister rust
      and has resulted in a dramatic reduction of native white pines across North
      America. Quantitative disease resistance (QDR) is a highly desirable trait
      screened in breeding programs for durable resistance against C. ribicola. Along
      with phenotyping on a collection of germplasms, we analyzed PmAMP1 transcript and
      protein expression and re-sequenced the full-length gene including its promoter
      region. A mixed linear model was used to identify the association of single
      nucleotide polymorphisms (SNPs) with accumulated protein and stem QDR levels.
      Among 16 PmAMP1 SNPs identified in the present study, we found an association of
      protein levels with 6 SNPs (P < 0.05), including 2 in the 5'-untranslated region
      (UTR), 3 in the open reading frame (ORF) region with 2 nonsynonymous SNPs, and 1
      SNP in the 3'-UTR. Another set of six SNPs was associated with stem QDR levels (P
      < 0.05), with one localized in the promoter region and the other five in the ORF
      region with four nonsynonymous changes, suggesting that multiple isoforms may
      have antifungal activity to differing degrees. Of three common PmAMP1 haplotypes,
      the trees with haplotype 2 showed high QDR levels with moderate protein abundance
      while those trees with haplotype 3 exhibited low QDR levels in the susceptible
      range and the lowest level of protein accumulation. Thus, an association of gene
      variations with protein abundance and resistance-related traits may facilitate
      elucidation of physiological contribution of PmAMP1 to host resistance.

PMID- 22968910
TI  - Plant acclimation to elevated CO2 affects important plant functional traits, and
      concomitantly reduces plant colonization rates by an herbivorous insect.
AB  - Plants growing under elevated CO2 concentration may acclimatize to this
      environmental change by modification of chemical, physiological, and/or
      morphological traits. As a consequence, not only plant functioning but also plant
      insect interactions might be altered, with important consequences particularly
      for agricultural systems. Whereas most studies have focused on the plant
      acclimation effects of elevated CO2 with regard to crop growth and productivity,
      acclimation effects on the behavioral response of insects associated with these
      plants have been largely neglected. In this study, we used a model system
      comprised of Brussels sprout Brassica oleraceae var. gemmifera and a specialized
      herbivorous insect, the cabbage aphid Brevicoryne brassicae, to test for the
      effects of various periods of exposure to an elevated (2* ambient) CO2
      concentration on key plant functional traits and on host plant location behavior
      by the insect, assessed as plant colonization rates. Elevated CO2 had no
      measurable effect on colonization rates or total plant volatile emissions after a
      2-week exposure, but it led to 15 and 26 % reductions in plant colonization rates
      after 6- and 10-week exposures, respectively. This reduction in plant
      colonization was associated with significant decreases in leaf stomatal
      conductance and plant volatile emission. Terpene emission, in particular,
      exhibited a great reduction after the 10-week exposure to elevated CO2. Our
      results provide empirical evidence that plants might acclimatize to a future
      increase in CO2, and that these acclimation responses might affect host plant
      choice and colonization behavior by herbivorous insects, which might be
      advantageous from the plant's perspective.

PMID- 22968912
TI  - Vertebrate nucleoplasmin and NASP: egg histone storage proteins with multiple
      chaperone activities.
AB  - Recent reviews have focused on the structure and function of histone chaperones
      involved in different aspects of somatic cell chromatin metabolism. One of the
      most dramatic chromatin remodeling processes takes place immediately after
      fertilization and is mediated by egg histone storage chaperones. These include
      members of the nucleoplasmin (NPM2/NPM3), which are preferentially associated
      with histones H2A-H2B in the egg and the nuclear autoantigenic sperm protein
      (NASP) families. Interestingly, in addition to binding and providing storage to
      H3/H4 in the egg and in somatic cells, NASP has been shown to be a unique genuine
      chaperone for histone H1. This review revolves around the structural and
      functional roles of these two families of chaperones whose activity is modulated
      by their own post-translational modifications (PTMs), particularly
      phosphorylation. Beyond their important role in the remodeling of paternal
      chromatin in the early stages of embryogenesis, NPM and NASP members can interact
      with a plethora of proteins in addition to histones in somatic cells and play a
      critical role in processes of functional cell alteration, such as in cancer.
      Despite their common presence in the egg, these two histone chaperones appear to
      be evolutionarily unrelated. In contrast to members of the NPM family, which
      share a common monophyletic evolutionary origin, the different types of NASP
      appear to have evolved recurrently within different taxa.

PMID- 22968911
TI  - Evolution of GOLDEN2-LIKE gene function in C(3) and C (4) plants.
AB  - A pair of GOLDEN2-LIKE transcription factors is required for normal chloroplast
      development in land plant species that encompass the range from bryophytes to
      angiosperms. In the C(4) plant maize, compartmentalized function of the two GLK
      genes in bundle sheath and mesophyll cells regulates dimorphic chloroplast
      differentiation, whereas in the C(3) plants Physcomitrella patens and Arabidopsis
      thaliana the genes act redundantly in all photosynthetic cells. To assess whether
      the cell-specific function of GLK genes is unique to maize, we analyzed gene
      expression patterns in the C(4) monocot Sorghum bicolor and C(4) eudicot Cleome
      gynandra. Compartmentalized expression was observed in S. bicolor, consistent
      with the development of dimorphic chloroplasts in this species, but not in C.
      gynandra where bundle sheath and mesophyll chloroplasts are morphologically
      similar. The generation of single and double mutants demonstrated that GLK genes
      function redundantly in rice, as in other C(3) plants, despite the fact that GLK
      gene duplication in monocots preceded the speciation of rice, maize and sorghum.
      Together with phylogenetic analyses of GLK gene sequences, these data have
      allowed speculation on the evolutionary trajectory of GLK function. Based on
      current evidence, most species that retain single GLK genes belong to orders that
      contain only C(3) species. We therefore propose that the ancestral state is a
      single GLK gene, and hypothesize that GLK gene duplication enabled sub
      functionalization, which in turn enabled cell-specific function in C(4) plants
      with dimorphic chloroplasts. In this scenario, GLK gene duplication
      preconditioned the evolution of C(4) physiology that is associated with
      chloroplast dimorphism.

PMID- 22968913
TI  - Twenty-eight days at 3454-m altitude diminishes respiratory capacity but enhances
      efficiency in human skeletal muscle mitochondria.
AB  - Modifications of skeletal muscle mitochondria following exposure to high altitude
      (HA) are generally studied by morphological examinations and biochemical analysis
      of expression. The aim of this study was to examine tangible measures of
      mitochondrial function following a prolonged exposure to HA. For this purpose,
      skeletal muscle biopsies were obtained from 8 lowland natives at sea level (SL)
      prior to exposure and again after 28 d of exposure to HA at 3454 m. High
      resolution respirometry was performed on the muscle samples comparing respiratory
      capacity and efficiency. Exercise capacity was assessed at SL and HA.
      Respirometric analysis revealed that mitochondrial respiratory capacity
      diminished in complex I- and complex II-specific respiration in addition to a
      loss of maximal state-3 oxidative phosphorylation capacity from SL to HA, all
      independent from alterations in mitochondrial content. Leak control coupling,
      respiratory control ratio, and oligomycin-induced leak respiration, all measures
      of mitochondrial efficiency, improved in response to HA exposure. SL respiratory
      capacities correlated with measures of exercise capacity near SL, whereas
      mitochondrial efficiency correlated best with exercise capacity following HA.
      This data demonstrate that 1 mo of exposure to HA reduces respiratory capacity in
      human skeletal muscle; however, the efficiency of electron transport improves.

PMID- 22968914
TI  - Cell adhesion and osteogenic differentiation on three-dimensional pillar
      surfaces.
AB  - We hypothesized that when compared with conventional two-dimensional (2D)
      cultures, substrates containing 3D micropillars would allow cells to grow at
      levels, activating their cytoskeleton to promote osteogenesis. Fibroblasts,
      osteoblast-like cells, and mesenchymal stem cells (MSCs) were studied. Planar
      substrates were compared with 200-nm-, 5-MUm-, and 20-MUm-high pillars of
      Ormocomp(r), Si, diamond-like carbon, or TiO(2). Scanning electron microscopy and
      staining of actin cytoskeleton showed 7.5-h adhesion to pillar edges and 5-day
      stretching between adhesion contacts > 100-MUm distances of fibroblast and MSC in
      3D networks, whereas SaOS-2 cells adhered flatly and individually on horizontal
      and vertical surfaces. ERK and ROCK immunostaining at 14 and 21 days confirmed
      activation of the cytoskeleton. In contrast to expectations, success to induce
      osteogenesis was dominated by the cytocompatibility of the substrate over the 3D
      structure. This was shown using early alkaline phosphatase, intermediate
      osteopontin, and late mineralization markers, together with bone nodule
      formation, which were seen in planar substrates and low-profile TiO(2) pillars,
      but were poor in the 20-MUm landscape. The lack of intercellular contacts seems
      to halt the osteogenesis-promoting effects of cytoskeletal organization and
      tension described earlier.

PMID- 22968915
TI  - STM manipulation of a subphthalocyanine double-wheel molecule on Au(111).
AB  - A new class of double-wheel molecules is manipulated on a Au(111) surface by the
      tip of a scanning tunneling microscope (STM) at low temperature. The double-wheel
      molecule consists of two subphthalocyanine wheels connected by a central rotation
      carbon axis. Each of the subphthalocyanine wheels has a nitrogen tag to monitor
      its intramolecular rolling during an STM manipulation sequence. The position of
      the tag can be followed by STM, allowing us to distinguish between the different
      lateral movements of the molecule on the surface when manipulated by the STM tip.

PMID- 22968916
TI  - Ceria nanoparticles that can protect against ischemic stroke.
AB  - Uniform 3 nm-sized ceria nanoparticles can protect against ischemic stroke by
      scavenging reactive oxygen species (ROS) and reducing apoptosis. PEGylated ceria
      nanoparticles showed protective effects against ROS-induced cell death in vitro.
      Optimal doses of ceria nanoparticles reduced infarct volumes and the rate of
      ischemic cell death in vivo.

PMID- 22968917
TI  - Solid immersion facilitates fluorescence microscopy with nanometer resolution and
      sub-angstrom emitter localization.
AB  - Exploring the maximum spatial resolution achievable in far-field optical imaging,
      we show that applying solid immersion lenses (SIL) in stimulated emission
      depletion (STED) microscopy addresses single spins with a resolution down to 2.4
      +/- 0.3 nm and with a localization precision of 0.09 nm.

PMID- 22968918
TI  - Application of supramolecular bidentate hybrid ligands in asymmetric
      hydroformylation.
AB  - In this study we report a novel class of supramolecular bidentate hybrid ligands
      in which the two inequivalent phosphorus units and pyridine moieties are
      covalently attached to a chiral scaffold and the supramolecular interactions are
      used as a second handle to control the coordination sphere around the transition
      metal centre. The coordination chemistry of these ligands was investigated under
      hydroformylation conditions by high-pressure NMR and IR spectroscopy, revealing
      the formation of a single active species in which the phosphane ligand is in the
      axial position and the phosphoramidite adopts the equatorial position. These
      ligands were applied in the asymmetric Rh-catalysed hydroformylation of styrene
      and para-substituted analogues. In these hydroformylation reactions, modification
      of the electronic and steric properties of the zinc(II)-templates appear to have
      a significant influence on the activity and selectivity of the catalysis. In
      particular, zinc(II)-templates bearing more electron-withdrawing substituents led
      to an increase in enantioselectivity.

PMID- 22968920
TI  - Tethered ansa-bridged titanium complexes immobilized on 3-mercaptopropyl
      functionalized silica gel and their application for the hydrosilylation of
      imines.
AB  - Four tethered titanocene complexes were covalently immobilized onto 3
      mercaptopropyl-functionalized silica gel. We have investigated the influence of
      the length of the tether and of the ansa-bridge on the activity in the
      heterogeneous hydrosilylation of the cyclic imine 2-phenylpyrroline, taken as an
      illustrative example. Possible metal leaching during the reaction was
      investigated using ICP/OES, recycling studies and the three-phase test. The novel
      immobilized catalysts exhibit an activity similar to their homogeneous analogues
      in the tested hydrosilylation reactions with a TOF of ~20 h(-1). Furthermore, our
      results indicate that metal leaching is negligible under the applied reaction
      conditions.

PMID- 22968919
TI  - Azo-propofols: photochromic potentiators of GABA(A) receptors.
AB  - Shine and rise! GABA(A) receptors are ligand-gated chloride ion channels that
      respond to gamma-aminobutyric acid (GABA), which is the major inhibitory
      neurotransmitter of the mammalian central nervous system. Azobenzene derivatives
      of propofol, such as compound 1 (see scheme), increase GABA-induced currents in
      the dark form and lose this property upon light exposure and thus function as
      photochromic potentiators. Compound 1 can be employed as a light-dependent
      general anesthetic in translucent tadpoles.

PMID- 22968921
TI  - Stem cells from innate sexual but not acquired sexual planarians have the
      capability to form a sexual individual.
AB  - Planarian species may harbor as many as three populations with different
      reproductive strategies. Animals from innate asexual (AS) and innate sexual (InS)
      populations reproduce only by fission and cross-fertilization, respectively,
      whereas the third population switches seasonally between the two reproductive
      modes. AS worms can be experimentally sexualized by feeding them with minced InS
      worms; we termed the resulting animals "acquired sexual" (AqS) worms. Both AqS
      and InS worms exhibit sexualizing activity when used as feed, suggesting that
      they maintain their sexual state via endogenous sexualizing substances, although
      the mechanisms underlying determination of reproductive strategy and sexual
      switching in these metazoans remain enigmatic. Therefore, we compared the
      endogenous sexualizing activity of InS worms and AqS worms. First, we amputated
      mature worms and assessed if they could re-enter a sexual state. Regenerants of
      InS worms, but not AqS worms, were only sexual, indicating that sexual state
      regulation comprises two steps: (1) autonomous initiation of sexualizing
      substance production and (2) maintenance of the sexual state by continuous
      production of sexualizing substances. Next, InS neoblasts were characterized by
      transplantation, finding that they successfully engrafted, proliferated, and
      replaced all recipient cells. Under such conditions, the AS recipients of InS
      worm neoblasts, but not those of AqS worms, became sexual. These results clearly
      show that there is a neoblast-autonomous determination of reproductive strategy
      in planarians.

PMID- 22968922
TI  - SNP set association analysis for familial data.
AB  - Genome-wide association studies (GWAS) are a popular approach for identifying
      common genetic variants and epistatic effects associated with a disease
      phenotype. The traditional statistical analysis of such GWAS attempts to assess
      the association between each individual single-nucleotide polymorphism (SNP) and
      the observed phenotype. Recently, kernel machine-based tests for association
      between a SNP set (e.g., SNPs in a gene) and the disease phenotype have been
      proposed as a useful alternative to the traditional individual-SNP approach, and
      allow for flexible modeling of the potentially complicated joint SNP effects in a
      SNP set while adjusting for covariates. We extend the kernel machine framework to
      accommodate related subjects from multiple independent families, and provide a
      score-based variance component test for assessing the association of a given SNP
      set with a continuous phenotype, while adjusting for additional covariates and
      accounting for within-family correlation. We illustrate the proposed method using
      simulation studies and an application to genetic data from the Genetic
      Epidemiology Network of Arteriopathy (GENOA) study. 

PMID- 22968923
TI  - Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial
      than in sporadic breast cancer.
AB  - Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision
      pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and
      nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non
      BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic and 39 familial
      breast cancer cases. The two groups were matched for hormone receptor status and
      human epidermal growth factor receptor 2 status. Additionally, they were matched
      by grading with a maximum difference of +/-1 degree (e.g., G2 instead of G3).
      Cytoplasmic PARP (cPARP) expression was significantly higher in familial compared
      to sporadic breast cancer (P = 0.008, chi-squared test for trends) and a high
      nuclear PARP expression (nPARP) was significantly more frequently observed in
      familial breast cancer (64 %) compared with sporadic breast cancer (36 %) (P =
      0.005, chi-squared test). The overall PARP expression was significantly higher in
      familial breast cancer (P = 0.042, chi-squared test). In familial breast cancer,
      a combination of high cPARP and high nPARP expression is the most common (33 %),
      whereas in sporadic breast cancer, a combination of low cPARP and intermediate
      nPARP expression is the most common (39 %). Our results show that the overall
      PARP expression in familial breast cancer is higher than in sporadic breast
      cancer which might suggest they might respond better to treatment with PARP
      inhibitors.

PMID- 22968924
TI  - Neonatal hyperimmune T-cell reaction mimicking T-cell non-Hodgkin's lymphoma
      following BCG and hepatitis B co-vaccination.
AB  - We describe a case of a 2-week-old male infant who presented with a rapidly
      enlarging inguinal mass after having received both the bacille Calmette-Guerin
      (BCG) and hepatitis B vaccines at birth. The clinical picture raised suspicion of
      a neoplasm, and an excision biopsy was performed. It showed complete effacement
      of the lymph node architecture by a diffuse proliferation of monomorphic,
      mitotically active, and medium-sized T-cell blasts with strong expression of
      CD99. Coalescent necrotizing granulomas were also seen. The lymph node culture
      was negative for BCG. Upon expert review and additional molecular diagnostics,
      the initial pathological diagnosis of lymphoblastic T-cell lymphoma was changed
      to ectopic BCG lymphadenitis and hyperimmune post-vaccinal reaction. The atypical
      T-cell proliferation was most likely a result of the adjuvant effects of the co
      administered vaccines. Post-vaccinal reactions usually involve the injection site
      or result in localized lymph node enlargements in the areas draining the
      inoculation site. This case highlights the importance of the clinical context for
      accurate interpretation of the pathological findings. In the setting of post
      vaccinal lymphadenopathy, a biopsy is rarely needed but, when performed, should
      be interpreted with great caution.

PMID- 22968925
TI  - Novel selenium-doped hydroxyapatite coatings for biomedical applications.
AB  - Nowadays there is a short-term need of investigating in orthopedic implants with
      a greater functionality, including an improved osseointegration and also
      antibacterial properties. The coating of metallic implants with hydroxyapatite
      (HA) remains to be the main proposal, but superior quality HA coatings with
      compositions closer to natural bone apatites, including carbonates, trace
      elements are required. Selenium is an essential nutrient in biological tissues
      and, at the same time, it also presents antibacterial properties. A pioneering
      study on the fabrication of selenium-doped carbonated hydroxyapatite (iHA:Se)
      coatings by Pulsed Laser Deposition (PLD) is presented. Different proportions of
      selenium were incorporated to obtain the iHA:Se coatings. Their physicochemical
      characterization, performed by SEM/EDS, FTIR, FT-Raman, Interferometric
      Profilometry and XPS, revealed typical columnar growth of HA in globular
      aggregates and the efficient incorporation of selenium into the HA coatings by
      the, most probably, substitution of SeO(3)(2-) groups in the CO(3)(2-) sites.
      Biological evaluation illustrated the absence of cytotoxicity when an amount of
      0.6 at.% of Se was added to the iHA:Se coatings and excellent proliferation of
      the MC3T3-E1 preosteoblasts. Antibacterial properties were also proved with the
      inhibition of P. aeruginosa and S. aureus from establishing bacterial biofilms.

PMID- 22968927
TI  - Incidence and costs of family member hospitalization following injuries of
      workers' compensation claimants.
AB  - BACKGROUND: The consequences of occupational injuries for the health of family
      members have rarely been studied. We hypothesized that non-fatal occupational
      injury would increase the incidence and costs of hospitalization among workers'
      families, and that family members of severely injured workers would be likely to
      experience greater increases in hospitalizations than family members of non
      severely injured workers. DATA AND METHODS: We used the MarketScan databases from
      Thomson Reuters for 2002-2005, which include workers' compensation and inpatient
      medical care claims data for injured workers' families. We used a before-after
      analysis to compare the odds and costs of family hospitalization 3 months before
      and after the index occupational injury among 18,411 families. Severe injuries
      were defined by receipt of indemnity payments and at least 7 days of lost work.
      Family hospitalizations were measured by the incidence of hospitalization of at
      least one family member. RESULTS: Among families of all injured workers, the odds
      of at least one family member being hospitalized were 31% higher [95% confidence
      intervals (CI) = 1.11-1.55] in the 3 months following occupational injury than in
      the 3 months preceding injury. Among the families of severely injured workers,
      the odds of hospitalization were 56% higher [95% CI = 1.05-2.34] in the 3 months
      following injury. Hospitalization costs were found to rise by approximately the
      same percentage as hospitalization incidence. CONCLUSION: The impact of
      occupational injury may extend beyond the workplace and adversely affect the
      health and inpatient medical care use of family members.

PMID- 22968926
TI  - Neurophysiological differences in reward processing in anhedonics.
AB  - Anhedonia is characterized by a reduced capacity to experience pleasure in
      response to rewarding stimuli and has been considered a possible candidate
      endophenotype in depression and schizophrenia. However, it is still not well
      understood whether these reward deficits are confined to anticipatory and/or to
      consummatory experiences of pleasure. In the present study, we recorded
      electrophysiological responses (event-related brain potentials [ERPs] and
      oscillatory activity) to monetary gains and losses in extreme groups of anhedonic
      and nonanhedonic participants. The anhedonic participants showed reduced
      motivation to incur risky decisions, especially after monetary rewards. These
      sequential behavioral effects were correlated with an increased sensitivity to
      punishment, which psychometrically characterized the anhedonic group. In
      contrast, both electrophysiological measures associated with the impacts of
      monetary losses and gains--the feedback-related negativity (FRN) and the beta
      gamma oscillatory component--clearly revealed preserved consummatory responses in
      anhedonic participants. However, anhedonics showed a drastic increase in frontal
      medial theta power after receiving the maximum monetary gain. This increase in
      theta oscillatory activity could be associated with an increase in conflict and
      cognitive control for unexpected large positive rewards, thus indexing the
      violation of default negative expectations built up across the task in anhedonic
      participants. Thus, the present results showed that participants with elevated
      scores on Chapman's Physical Anhedonia Scale were more sensitive to possible
      punishments, showed deficits in the correct integration of response outcomes in
      their actions, and evidenced deficits in sustaining positive expectations of
      future rewards. This overall pattern suggests an effect of anhedonia in the
      motivational aspects of approach behavior rather than in consummatory processes.

PMID- 22968928
TI  - Convergent chemical synthesis of proteins by ligation of peptide hydrazides.

PMID- 22968930
TI  - Asymmetric total synthesis of (-)-stenine and 9a-epi-stenine.
AB  - A route for the asymmetric synthesis of (-)-stenine, a member of the Stemona
      alkaloid family used as folk medicine in Asian countries, is described. The key
      features of the sequence employed include stereoselective transformations on a
      cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular
      Mitsunobu reaction to construct the perhydroindole ring system. By using an
      intermediate in the route to (-)-stenine, an asymmetric synthesis of 9a-epi
      stenine was also executed. The C(9a) stereocenter in 9a-epi-stenine was installed
      by using a Staudinger/aza-Wittig reaction of a keto-azide precursor followed by
      reduction of the resulting imine. The results of this effort demonstrate the
      applicability of the chiral auxiliary based strategy to the preparation of
      naturally occurring alkaloids that contain highly functionalized cyclohexane
      cores.

PMID- 22968931
TI  - Biomimetic oxidative coupling of benzylamines and 2-aminophenols: synthesis of
      benzoxazoles.
AB  - Aerobic oxidation: in a biomimetic approach, a mixture of redox catalysts forms
      couples that effect the aerobic oxidation of a mixture of benzylamine and 2
      aminophenol derivatives to give the corresponding benzoxazoles. This biomimetic
      oxidation proceeds smoothly under mild conditions and the protocol can also be
      used for preparing benzimidazoles and benzothiazoles.

PMID- 22968929
TI  - Extensive somatic L1 retrotransposition in colorectal tumors.
AB  - L1 retrotransposons comprise 17% of the human genome and are its only autonomous
      mobile elements. Although L1-induced insertional mutagenesis causes Mendelian
      disease, their mutagenic load in cancer has been elusive. Using L1-targeted
      resequencing of 16 colorectal tumor and matched normal DNAs, we found that
      certain cancers were excessively mutagenized by human-specific L1s, while no
      verifiable insertions were present in normal tissues. We confirmed de novo L1
      insertions in malignancy by both validating and sequencing 69/107 tumor-specific
      insertions and retrieving both 5' and 3' junctions for 35. In contrast to
      germline polymorphic L1s, all insertions were severely 5' truncated. Validated
      insertion numbers varied from up to 17 in some tumors to none in three others,
      and correlated with the age of the patients. Numerous genes with a role in
      tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus,
      somatic retrotransposition may play an etiologic role in colorectal cancer.

PMID- 22968932
TI  - Spin current in an electron waveguide tunnel-coupled to a topological insulator.
AB  - We show that electron tunneling from edge states in a two-dimensional topological
      insulator into a parallel electron waveguide leads to the appearance of spin
      polarized current in the waveguide. The spin polarization P can be very close to
      unity and the electron current passing through the tunnel contact splits in the
      waveguide into two branches flowing from the contact. The polarization
      essentially depends on the electron scattering by the contact and the electron
      electron interaction in the one-dimensional edge states. The electron-electron
      interaction is treated within the Luttinger liquid model. The main effect of the
      interaction stems from the renormalization of the electron velocity, due to which
      the polarization increases with the interaction strength. Electron scattering by
      the contact leads to a decrease in P. A specific effect occurs when the bottom of
      the subbands in the waveguide crosses the Dirac point of the spectrum of edge
      states when changing the voltage or chemical potential. This leads to changing
      the direction of the spin current.

PMID- 22968933
TI  - Using host-guest complexation to fold a flexible linear organic string:
      kinetically controlled syntheses of [3]catenanes and a five-membered molecular
      necklace.

PMID- 22968935
TI  - Prediction of physical-chemical properties of crude oils by 1H NMR analysis of
      neat samples and chemometrics.
AB  - In this work, we report the feasibility study to predict the properties of neat
      crude oil samples from 300-MHz NMR spectral data and partial least squares (PLS)
      regression models. The study was carried out on 64 crude oil samples obtained
      from 28 different extraction fields and aims at developing a rapid and reliable
      method for characterizing the crude oil in a fast and cost-effective way. The
      main properties generally employed for evaluating crudes' quality and behavior
      during refining were measured and used for calibration and testing of the PLS
      models. Among these, the UOP characterization factor K (K(UOP)) used to classify
      crude oils in terms of composition, density (D), total acidity number (TAN),
      sulfur content (S), and true boiling point (TBP) distillation yields were
      investigated. Test set validation with an independent set of data was used to
      evaluate model performance on the basis of standard error of prediction (SEP)
      statistics. Model performances are particularly good for K(UOP) factor, TAN, and
      TPB distillation yields, whose standard error of calibration and SEP values match
      the analytical method precision, while the results obtained for D and S are less
      accurate but still useful for predictions. Furthermore, a strategy that reduces
      spectral data preprocessing and sample preparation procedures has been adopted.
      The models developed with such an ample crude oil set demonstrate that this
      methodology can be applied with success to modern refining process requirements.

PMID- 22968937
TI  - Under pressure.
AB  - Physical urticaria is a rare but challenging subset of chronic urticaria. Wheals
      of pressure urticaria are typically delayed in appearance. A pressure test can
      easily be done to confirm the diagnosis.

PMID- 22968936
TI  - Educational paper: Progression in chronic kidney disease and prevention
      strategies.
AB  - Chronic kidney disease (CKD) in children is a rare but devastating condition.
      Once a critical amount of nephron mass has been lost, progression of CKD is
      irreversible and results in end-stage renal disease (ESRD) and need of renal
      replacement therapy. The time course of childhood CKD is highly variable. While
      in children suffering from congenital anomalies of the kidneys and the urinary
      tract, progression of CKD in general is slow, in children with acquired
      glomerulopathies, disease progression can be accelerated resulting in ESRD within
      months. However, irrespective of the underlying kidney disease, hypertension and
      proteinuria are independent risk factors for progression. Thus, in order to
      prevent progression, the primary objective of treatment should always aim for
      efficient control of blood pressure and reduction of urinary protein excretion.
      Blockade of the renin-angiotensin-aldosterone system preserves kidney function
      not only by lowering blood pressure, but also by reducing proteinuria and
      exerting additional anti-proteinuric, anti-fibrotic, and anti-inflammatory
      effects. Besides, intensified blood pressure control, aiming for a target blood
      pressure below the 50th percentile, may exert additive renoprotective effects.
      Additionally, other modifiable risk factors, such as anemia, metabolic acidosis,
      dyslipidemia, and altered bone-mineral homeostasis may also contribute to CKD
      progression. In conclusion, beyond strict blood pressure control and reduction of
      urinary protein excretion, identification and treatment of both, renal disease
      related and conventional risk factors are mandatory in children with CKD in order
      to prevent deterioration of kidney function.

PMID- 22968938
TI  - Study of the effect of membrane thickness on microcapsule strength, permeability,
      and cell proliferation.
AB  - Cell microencapsulation is one of the promising strategies for in vitro
      production of proteins or in vivo delivery of therapeutic products. Membrane
      thickness controls microcapsule strength and permeability, which may in return
      affect cell growth and metabolism. In this study, the strength, permeability, and
      encapsulated Chinese hamster ovary cell proliferation and metabolism of four
      groups of microcapsules with different membrane thicknesses were investigated. It
      was found that increasing membrane thickness increases microcapsule strength,
      whereas decreases membrane permeability. During the first 6 days, cells within
      microcapsules with 10 MUm thickness membrane proliferated fast and could reach a
      cell density of 1.9 * 10(7) cells/mL microcapsule with 92% cell density. A cell
      density of 5.5 * 10(7) cells/mL microcapsule with >85% cell density was achieved
      within microcapsules with 15 MUm membrane thickness and these microcapsules kept
      over 88% integrity ratio after 11 days, which was much higher than that of
      microcapsules with 10 MUm membrane thickness. Membrane with more than 20 MUm
      thickness was not suited for encapsulated cell culture owing to low-protein
      diffusion rate. These results indicated that cells survived shortly within the
      thinnest membrane thickness. There was a specific membrane thickness more
      suitable for cell growth for a long-time culture. These findings will be useful
      for preparing microcapsules with the desired membrane thickness for
      microencapsulated cell culture dependent on various purposes.

PMID- 22968939
TI  - Scarring and mortality selection among Civil War POWs: a long-term mortality,
      morbidity, and socioeconomic follow-up.
AB  - Debilitating events could leave either more frail or more robust survivors,
      depending on the extent of scarring and mortality selection. The majority of
      empirical analyses find more frail survivors. I find heterogeneous effects. Among
      severely stressed former Union Army prisoners of war (POWs), the effect that
      dominates 35 years after the end of the Civil War depends on age at imprisonment.
      Among survivors to 1900, those younger than 30 at imprisonment faced higher old
      age mortality and morbidity and worse socioeconomic outcomes than non-POW and
      other POW controls, whereas those older than 30 at imprisonment faced a lower
      older-age death risk than the controls.

PMID- 22968940
TI  - Bifunctional 3D Cu-MOFs containing glutarates and bipyridyl ligands: selective
      CO2 sorption and heterogeneous catalysis.
AB  - We report bifunctional three-dimensional (3D) Cu-MOFs with high selectivity of
      CO(2) over N(2) and H(2) as well as high catalytic activity for
      transesterification of esters. The Cu-MOFs containing Cu(2) dinuclear units
      connected by glutarates and bipyridyl ligands are formulated as
      [{Cu(2)(Glu)(2)(MU-bpa)}.(CH(3)CN)](n) (1) and [{Cu(2)(Glu)(2)(MU
      bpp)}.(C(3)H(6)O)](n) (2) (Glu = glutarate, bpa = 1,2-bis(4-pyridyl)ethane, bpp =
      1,3-bis(4-pyridyl)propane). These two new bifunctional 3D Cu-MOFs possess very
      similar pore shape with different pore dimensions. Their gas sorption behaviors
      were investigated by using CO(2), N(2) and H(2) at suitable temperatures. Both
      MOFs exhibited good CO(2) selectivity over N(2) and H(2). MOF 1 having a smaller
      pore dimension exhibited much higher CO(2) adsorption enthalpy than MOF 2 having
      a larger pore dimension. However, MOF 2 exhibited more enhanced CO(2) uptake
      ability than MOF 1. A subtle variation of pore dimension indeed influenced the
      CO(2) uptake ability somewhat significantly especially at higher temperatures
      such as 273 K and 298 K. Heterogeneous catalytic activities of the MOFs were also
      investigated in detail. Only MOF 1 appeared to be an efficient, mild, and easily
      recyclable heterogeneous catalyst for the transesterification of esters and
      constitutes a promising class of heterogeneous catalysts that allowed reuse
      without a significant loss of activity through twenty runs with ester.

PMID- 22968941
TI  - Synthesis and characterization of nanostructured Fe3O4 micron-spheres and their
      application in removing toxic Cr ions from polluted water.
AB  - We present a simple and effective method for the synthesis of nanostructured
      Fe(3)O(4) micron-spheres (NFMSs) by annealing hydrothermally formed FeCO(3)
      spheres in argon. The phase structure, particle size, and magnetic properties of
      the product have been characterized by X-ray diffraction (XRD), Fourier-transform
      infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), field
      emission scanning electron microscopy (FESEM), transmission electron microscopy
      (TEM), and by means of a superconducting quantum interference device (SQUID). The
      results have shown that the as-obtained NFMSs have a diameter of about 5 MUm and
      are composed of nanometer-sized porous lamellae. The NFMSs have a large specific
      surface area (135.9 m(2) g(-1)), reductive Fe(2+) incorporated into their
      structure, and intense magnetic properties. These properties suggest that NFMSs
      have potential application in removing toxic Cr(6+) ions from polluted water. At
      25 degrees C, each gram of NFMSs product can remove 43.48 mg of Cr(6+) ions, as
      compared to just 10.2 mg for nanometer-sized Fe(3)O(4) and 1.89 mg for micron
      sized Fe(3)O(4). The enhanced removal performance can be ascribed to the
      structural features. Moreover, the Cr(6+) ion removal capacity of the NFMSs can
      reach up to 71.2 mg g(-1) at 50 degrees C. The influencing parameters in the
      removal of Cr(6+) ions, such as contact time, pH, and temperature, have been
      evaluated. The Cr(6+)-removal mechanism has been investigated. We have found that
      the NFMSs product not only serves as an effective adsorbent to remove toxic
      Cr(6+) ions from polluted water, but also as an effective reductant in reducing
      the adsorbed toxic Cr(6+) ions to much less toxic Cr(3+) through the Fe(2+)
      incorporated into its structure.

PMID- 22968942
TI  - Bacterial synthesis of diverse indole terpene alkaloids by an unparalleled
      cyclization sequence.

PMID- 22968943
TI  - Dendrimer functionalization with a membrane-interacting domain of herpes simplex
      virus type 1: towards intracellular delivery.
AB  - A poly(amide)-based dendrimer was synthesized and functionalized with the
      membrane-interacting peptide gH(625-644) (gH625) derived from the herpes simplex
      virus type 1 (HSV-1) envelope glycoprotein H, which has previously been shown to
      assist in delivering large cargoes across the cellular membrane. We demonstrate
      that the attachment of the gH625 peptide sequence to the termini of a dendrimer
      allows the conjugate to penetrate into the cellular matrix, whereas the
      unfunctionalized dendrimer is excluded from translocation. The peptide
      functionalized dendrimer is rapidly taken into the cells mainly through a non
      active translocation mechanism. Our results suggest that the presented
      peptidodendrimeric scaffold may be a promising material for efficient drug
      delivery.

PMID- 22968944
TI  - Older farmers and machinery exposure-cause for concern?
AB  - BACKGROUND: The average age of farmers in North America is increasing each year.
      We had the unique opportunity to examine work patterns and how they change across
      the lifespan in a large cohort of farm operations. METHODS: Saskatchewan farms
      were surveyed via questionnaire during the winter of 2007 to examine the
      determinants of injury. A sub-sample of 2,751 male farmers aged 25 and older was
      used in this project. The primary dependent variable was the proportion of work
      time devoted to specific farm tasks which was related to advancing age. RESULTS:
      The weekly hours of work declined approximately 34% as farmers aged over the
      lifespan. Older farmers disproportionately retained tasks involving tractors and
      combines as they aged, so that the proportion of time spent operating machinery
      such as tractors and combines increased by about 40% in the older age groups.
      CONCLUSION: Exposure to potentially dangerous farm equipment does not decrease as
      much as would be expected based on an equal linear reduction in all work tasks as
      overall work quantity decreases with age. Older farmers remain relatively active
      in the workplace, and, therefore, prevention efforts should focus on safe
      machinery operation.

PMID- 22968945
TI  - Electronic structure and magnetism of La4Ni3O8 from first principles.
AB  - The magnetic and electronic properties of La(4)Ni(3)O(8) are investigated by
      performing the full-potential linearized augmented plane wave method. The C-type
      antiferromagnetic spin ordering is preferred and a molecular correlated
      insulating state with high-spin Ni ions is found. Our results have proved that
      this insulating state is caused by a correlation effect and the strong interlayer
      interaction. Such strong interlayer coupling results from the high-spin
      occupation of Ni ions.

PMID- 22968946
TI  - The synthesis of eta-1,2,3,4,5,6-hexafluorocyclohexane (benzene hexafluoride)
      from benzene.

PMID- 22968947
TI  - Gene profiling of inflammatory genes in day 18 endometria from pregnant and non
      pregnant mares.
AB  - Maternal recognition of pregnancy is a physiological process that primarily
      describes endometrial responses to a conceptus. Recognition of a conceptus
      prevents the release of prostaglandin F(2alpha) , thereby ensuring survival of
      the corpus luteum and continued progesterone production. Exactly how this occurs
      in the mare is poorly understood. Because prostaglandin F(2alpha) is a pro
      inflammatory hormone, we hypothesized that differential gene expression in the
      endometrium at the time of maternal recognition reflects an anti-inflammatory
      event leading to decreased prostaglandin F(2alpha) secretion. Mares were
      inseminated, and endometrial biopsies were recovered from pregnant mares on Day
      18 post-ovulation. In subsequent estrous cycles, mares were not inseminated and
      Day 18 post-ovulation endometrial biopsies were collected (non-pregnant control,
      matched per individual). Endometrial gene expression profiles were examined by
      screening an Affymetrix equine GeneChip containing probes specific for genes
      related to inflammatory processes. Microarray analysis revealed 118 genes that
      were up-regulated and 93 genes that were down-regulated (P < 0.001) at least 1.5
      fold in the endometrium of pregnant versus non-pregnant mares. Quantitative, real
      time RT-PCR confirmed the microarray results for three up-regulated genes
      homologous to TSC22D3, PPAPDC2, and KLF6, and three down-regulated genes
      homologous to ESR1, MARCKSL1, and EPSTI1 (P < 0.05). It is concluded that the
      presence of the equine embryo induces differential gene expression in the
      endometrium of Day 18 pregnant mares, and that these genes are associated with
      inflammatory processes and pathways involving cellular growth and proliferation.
      The results from this study provide important new insights into endometrial gene
      expression in response to early equine pregnancy.

PMID- 22968948
TI  - First record of Lecithochirium grandiporum (Digenea: Hemiuridae) infecting the
      lizard fish Saurida tumbil from the Red Sea.
AB  - The present study was the first investigation of digenetic trematode parasites of
      Saurida tumbil, a commercially important fish species of the Red Sea, during the
      period from January to December 2011. Thirty-nine out of 103 (37.8 %) of the
      examined fish were found to harbor the digenetic trematode Lecithochirium
      grandiporum (family: Hemiuridae) infecting the pyloric portion of stomach and
      middle part of intestines of the lizard fish. The morphology and morphometric
      characterizations of this digenetic trematode were described by light and
      scanning electron microscopy. The parasite possessed a body which was elongated
      and rounded anteriorly, but truncated posteriorly, and its body measured 1.63 +/-
      0.20 (1.2-1.93) mm (invaginated ecsoma), 2.11 +/- 0.20 (1.83-2.35) mm (evaginated
      ecsoma) in length with a maximum width of 0.4 +/- 0.02 (0.31-0.52) mm at ovarian
      level. They were characterized by a subterminal oral sucker which measured 0.15
      +/- 0.02 (0.12-0.18) mm in diameter and was smaller than the ventral sucker which
      was circular and large with a wide aperture, hence the specific name grandiporum.
      A multilobated digitiform vitellarium which was a distinctive feature for this
      species was also observed. The number of parasite per fish was one to six.
      Prevalence and intensity of infection were positively correlated with host size
      (increasing with host size increasing). Host sex does not seem to affect the
      prevalence of infection. The present study was considered as a first record from
      the Red Sea in Egypt.

PMID- 22968949
TI  - Clinicopathological findings of a natural outbreak of Theileria annulata in
      cattle: an emerging disease in southern Iran.
AB  - Theileriosis is an economically important hemoprotozoal disease with high
      morbidity and mortality in cattle. The present study reported the pathological
      features of a natural outbreak of tropical bovine theileriosis due to Theileria
      annulata in Fars Province, southern Iran. T. annulata was confirmed by the
      presence of T. annulata piroplasms in the blood smears and also by polymerase
      chain reaction test. On necropsy, pale mucous membranes and petechial and
      ecchymotic hemorrhages in the mucosal and serosal surfaces together with
      lymphadenopathy were observed. The liver was friable, yellowish, and larger than
      normal. Hemorrhages and punched-out ulcers were observed in the abomasal mucous
      membrane. Severe petechial hemorrhages were seen in the skin particularly in the
      hairless areas. Pulmonary edema and emphysema with petechial and ecchymotic
      hemorrhagic foci in the lungs were evident. The main histological changes were
      proliferation of lymphocytes in the lymph nodes and proliferation of macrophages,
      lymphocytes, and plasma cells in the spleen, Peyer's patches, portal tracts of
      the liver, and interstitial tissue of the kidneys. The mucous membrane of the
      abomasum showed numerous multifocal areas of necrosis and ulceration, and the
      submucosal area and lamina propria adjacent to these lesions showed hyperemia and
      hemorrhages, with mononuclear cell infiltration. The skin showed multifocal
      necrotic changes, petechial and ecchymotic hemorrhages, and chronic dermatitis.
      The schizonts of Theileria were evident in the cytoplasm of the lymphocytes and
      macrophages of the lymph nodes, spleen, and skin. Molecular examination revealed
      that these animals were infected with T. annulata. The present study describes
      the clinicopathological findings of bovine tropical theileriosis in an
      unpredictable weather condition.

PMID- 22968950
TI  - A new versatile system for rapid control of gene expression in the fission yeast
      Schizosaccharomyces pombe.
AB  - The ability to regulate the expression of a gene greatly aids the process of
      uncovering its functions. The fission yeast Schizosaccharomyces pombe has so far
      lacked a system for rapidly controlling the expression of chromosomal genes,
      hindering its full potential as a model organism. Although the widely used nmt1
      promoter displays a wide dynamic range of activity, it takes > 14-15 h to
      derepress. The urg1 promoter also shows a large dynamic range and can be induced
      quickly (< 2 h), but its implementation requires laborious strain construction
      and it cannot be used to study meiosis. To overcome these limitations, we
      constructed a tetracycline-regulated system for inducible expression of
      chromosomal genes in fission yeast, which is easily established and implemented.
      In this system the promoter of a gene is replaced by simple one-step substitution
      techniques with a tetracycline-regulated promoter cassette (tetO(7) -TATA(CYC1) )
      in cells where TetR/TetR'-based transcription activators/repressors are also
      produced. Using top1 and nse6 as reporter genes, we show that Top1 and Nse6
      appear after just 30 min of activating tetO(7) -TATA(CYC1) and plateau after -4-6
      h. The amount of synthesised protein is comparable to that produced from the
      attenuated nmt1 promoter P(nmt8) , which should be closer to wild-type levels for
      most genes than those generated from excessively strong promoters and can be
      controlled by changing the concentration of the effector antibiotic. This system
      also works efficiently during meiosis, thus making it a useful addition to the
      toolkit of the fission yeast community.

PMID- 22968951
TI  - In vitro evaluation of hydroxyapatite-chitosan-gelatin composite membrane in
      guided tissue regeneration.
AB  - Resorbable biomaterials have been investigated as barrier membranes to
      compartmentalize the periodontal defects while selectively guiding
      osteoprogenitor cell proliferation and bone tissue expansion. Hydroxyapatite (H),
      chitosan (C), and gelatin (G) have chemical similarity to the structural
      components of natural bone and their composites have been tested as bone
      scaffolds. Human mesenchymal stem or stromal cells (hMSCs) are inducible
      osteoprogenitors and are responsible for bone tissue repair and regeneration. In
      this study, the dynamic interactions of hMSC with composite hydroxyapatite
      chitosan-gelatin (HCG) membranes were investigated. The association of HCG formed
      a biodegradable membrane with ~60 wt % water and an initial stiffness of ~20 kPa.
      Preconditioning in serum-containing media resulted in the formation nanopores in
      the HCG membranes and the increase of extracellular matrix (ECM) protein
      adsorption. Expression of integrin alpha(2)beta(1) and alpha(5)beta(1) coincided
      with ECM enrichment, suggesting the enhanced cell-ECM interactions. The elevated
      expression of bone marker proteins and genes in the HCG membranes suggests the
      progression of hMSC osteogenic differentiation in the absence of chemical
      induction. The results showed that the HCG membranes possess sufficient
      mechanical and structural properties to function as a barrier membrane, and that
      the adsorbed ECM proteins effectively functionalized the HCG membranes and
      promoted hMSC osteogenic differentiation.

PMID- 22968952
TI  - Ruthenium-catalyzed C6-propenylation reactions of substituted pyridine
      derivatives: directed and direct C-H activation.

PMID- 22968954
TI  - Excess healthcare costs associated with prior workers' compensation activity.
AB  - BACKGROUND: Workers compensation (WC) does not fully compensate workplace
      injuries and illnesses. This work examines whether cost shifting occurs to group
      health insurance for work-related injuries and illnesses. METHODS: Thomson
      Reuters MarketScan databases of medical insurance claims were used. WC and other
      benefit system data, employee status and types of medical insurance coverage were
      also available. Medical cost was analyzed using two-part models: the first part
      modeled the monthly probability of a worker having any group health medical
      claims, and the second part modeled the total monthly cost of those medical
      claims. Models included an estimate of a worker's annual medical costs prior to a
      WC claim. The predicted monthly medical costs were derived by retransformation
      using Duan's smearing factor. RESULTS: Individuals with prior WC claims were more
      likely to file a group health medical claim compared to those with no prior WC
      claims (OR = 1.25) and incurred a higher average monthly medical costs (among
      nonunion hourly men aged 18-34 years with prior WC claims: $203.72 vs. $160.29
      with no prior claim, an increase of $43). These increases were observed in all
      industrial sectors with the service sector having the highest monthly increase
      ($66). DISCUSSION: The results reveal that individuals with prior WC claims had
      higher probability of filing a group health medical claim and higher average
      monthly medical costs in all sectors. This suggests that a part of employer
      liability costs related to WC gets shifted to the group health medical insurance
      system.

PMID- 22968953
TI  - Identification of suitable culture condition for expansion and osteogenic
      differentiation of human bone marrow stem cells.
AB  - This study was undertaken in order to identify the best culture strategy to
      expand and osteogenic differentiation of human bone marrow stem cells (hBMSCs)
      for subsequent bone tissue engineering. In this regard, the experiment was
      designed to evaluate whether it is feasible to bypass the expansion phase during
      hBMSCs differentiation towards osteogenic lineages by early induction, if not
      identification of suitable culture media for enhancement of hBMSCs expansion and
      osteogenic differentiation. It was found that introduction of osteogenic factors
      in alpha-minimum essential medium (alphaMEM) during expansion phase resulted in
      significant reduction of hBMSCs growth rate and osteogenic gene expressions. In
      an approach to identify suitable culture media, the growth and differentiation
      potential of hBMSCs were evaluated in alphaMEM, F12:DMEM (1:1; FD), and FD with
      growth factors. It was found that alphaMEM favors the expansion and osteogenic
      differentiation of hBMSCs compared to that in FD. However, supplementation of
      growth factors in FD, only during expansion phase, enhances the hBMSCs growth
      rate and significantly up-regulates the expression of CBFA-1 (the early markers
      of osteogenic differentiation) during expansion, and, other osteogenic genes at
      the end of induction compared to the cells in alphaMEM and FD. These results
      suggested that the expansion and differentiation phase of the hBMSCs should be
      separately and carefully timed. For bone tissue engineering, supplementation of
      growth factors in FD only during the expansion phase was sufficient to promote
      hBMSCs expansion and differentiation, and preferably the most efficient culture
      condition.

PMID- 22968955
TI  - Insulator, semiclassical oscillations and quantum Hall liquids at low magnetic
      fields.
AB  - Magneto-transport measurements are performed on two-dimensional GaAs electron
      systems to probe the quantum Hall (QH) effect at low magnetic fields.
      Oscillations following the Shubnikov-de Haas (SdH) formula are observed in the
      transition from the insulator to QH liquid when the observed almost temperature
      independent Hall slope indicates insignificant interaction correction. Our study
      shows that the existence of SdH oscillations in such a transition can be
      understood based on the non-interacting model.

PMID- 22968956
TI  - No extensive experience in open procedures is needed to learn lobectomy by video
      assisted thoracic surgery.
AB  - OBJECTIVES: Lobectomies done by video-assisted thoracic surgery (VATS) result in
      fewer complications and less pain and save total costs compared with the
      traditional approach. However, the majority of procedures are still performed via
      open thoracotomies, because VATS lobectomy is considered difficult to learn,
      requiring experience in open surgery, and causing complications in the initial
      phase of the learning curve. The aim of this study was to describe a training
      model appreciating patient safety during training and to explore the initial
      learning curve for a trainee rather inexperienced in open surgery. METHODS: A
      trainee who had performed 14 lobectomies by thoracotomy was enrolled in a
      training programme at a high-volume VATS centre. The training model included
      courses and simulations followed by the selection of suitable patients operated
      on during close expert supervision. Data regarding time, a variety of quality
      indicators and complications were collected prospectively and compared with
      experts' performance. RESULTS: Over 12 months, 29 of 214 VATS lobectomies were
      performed by the trainee. Twice, the supervisor had to finish the procedure due
      to technical difficulties. None of the operations were converted to open
      thoracotomy. Compared with experts, the trainee operated significantly slower
      [median 120 (range 74-160) vs 100 (range 42-255) min, P = 0.04]; had similar
      perioperative bleeding [median 100 (range 10-500) vs 50 (range 5-2500) ml, P =
      0.79]; had earlier chest tube removal [median 1 (range 1-6) vs 2 (range 1-32)
      postoperative days, P < 0.001]; and reduced hospital stay [median 3 (range 1-10)
      vs 4 (range 1-41) days, P < 0.001]. Twenty-three (79%) patients had no
      complications, while 2 had atrial fibrillation. Pneumothorax after chest tube
      removal, incisional infection, prolonged pain and need for pleuracentesis were
      each seen once. CONCLUSIONS: With thorough preparation of trainees and training
      on selected patients under close supervision, the learning curve can be overcome
      with good results even if the trainee has limited prior experience in open
      surgery.

PMID- 22968957
TI  - Extracorporeal membrane oxygenation as a bridge to diagnosis in a 20-month old
      girl with pulmonary hypertension and right ventricular failure.
AB  - A 20-month old girl with severe pulmonary hypertension and cardiomegaly was
      admitted to the paediatric intensive care unit with right ventricular failure of
      unknown origin. Only after decompression of the heart chambers under
      extracorporeal membrane oxygenation (ECMO), did the pathognomonic membrane of Cor
      triatriatum become visible on echocardiography. The patient underwent successful
      surgical correction and subsequently cardiac function recovered completely. Cor
      triatriatum remains a rare congenital cardiac disorder with a variable
      presentation, often including recurrent respiratory infections before right-sided
      heart failure occurs. This case illustrates that ECMO can serve not only as a
      bridge to diagnosis, but can also facilitate correct diagnosis. Given the
      excellent outcome after surgical treatment, it is crucial that cardiologists rule
      out the possibility of cor triatriatum when assessing a child with unexplained
      pulmonary hypertension.

PMID- 22968958
TI  - Fibromuscular dysplasia of the brachial artery associated with unilateral
      clubbing.
AB  - A 46-year old male patient was admitted with a history of an extremely painful
      right upper arm, associated with unilateral clubbing. Duplex scanning and
      magnetic resonance imaging were suggestive of a pseudo-aneurysm of the brachial
      artery. Digital angiography showed an irregular brachial artery, associated with
      a small pseudo-aneurysm. The brachial artery was partially resected and
      reconstructed with a venous interposition graft. Pathological examination
      provided the final diagnosis of fibromuscular dysplasia. Although more
      encountered in women, this case report describes the occurrence of fibromuscular
      dysplasia in an unusual location in a male patient with a long-term follow-up.

PMID- 22968959
TI  - The role of combined carotid endarterectomy and coronary artery bypass grafting
      in the era of carotid stenting in view of long-term results.
AB  - OBJECTIVES: The management of concomitant coronary and carotid artery disease is
      still in evolution. The surgical options are staged approach--carotid
      endarterectomy (CEA), followed by coronary artery bypass grafting (CABG) or a
      reversed-staged approach, or combined approach--CEA and CABG under the same
      anaesthesia. In view of the percutaneous carotid artery stenting option, we have
      reviewed our short- and long-term experience with combined CEA and CABG to define
      the role of this procedure. METHODS: From January 1992 to December 2006, we
      operated on 80 patients performing combined carotid endarterctomy and myocardial
      revascularization. Short- and long-term results were reviewed. RESULTS: Operative
      mortality was 3.7%. Perioperative cerebrovascular accident (CVA) occurred in 2
      patients (2.5%). Perioperative myocardial infarction (MI) occurred in 3 patients
      (3.7%). Combined complications of death + MI + CVA = 10%. During the mean follow
      up of 10 +/- 3.2 years (1-14 years), 6 patients (7.6%) had neurological events.
      Freedom from neurological events for 10 years was 92 +/- 4%. Nearly 17 (21.5%)
      had cardiac events. The 5-year and 10-year survival rates were 74 +/- 5 and 62 +/
      6%, respectively. CONCLUSIONS: Although the short-term results of the non
      surgical carotid therapeutic alternative is similar to our surgical results,
      there are limitations to carotid artery stenting: the need for aggressive
      antiplatelets therapy, and the haemodynamic changes during the procedure that may
      be unacceptable for patients with unstable coronary artery disease. Therefore,
      there is still a role for concomitant surgical CEA and CABG to the results of
      which the other options should be compared.

PMID- 22968960
TI  - Red-emitting rhodamines with hydroxylated, sulfonated, and phosphorylated dye
      residues and their use in fluorescence nanoscopy.
AB  - Fluorescent dyes emitting red light are frequently used in conventional and super
      resolution microscopy of biological samples, although the variety of the useful
      dyes is limited. We describe the synthesis of rhodamine-based fluorescent dyes
      with absorption and emission maxima in the range of 621-637 and 644-660 nm,
      respectively and demonstrate their high performance in confocal and stimulated
      emission depletion (STED) microscopy. New dyes were prepared by means of reliable
      chemical transformations applied to a rhodamine scaffold with three variable
      positions. They feature polarity, water solubility, variable net charges,
      improved stabilities of N-hydroxysuccinimidyl (NHS) esters, as well as large
      fluorescence quantum yields in dye solutions and antibody conjugates. The
      photophysical and imaging properties of dyes containing three different polar
      groups, namely primary phosphate, sulfonic acid (in two different positions), and
      hydroxyl were compared. A dye with two primary phosphate groups was explored as a
      valuable alternative to dyes with "classical" sulfonic acid groups. Due to the
      increased net charge of the phosphorylated dye (q=-4 at pH 8), it demonstrated a
      far better electrophoretic mobility compared with analogues with two sulfonic
      acid groups (q=-2). As an example, one fluorescent dye was designed to be
      especially convenient for practical use. It is characterized by sufficiently high
      chemical stability of the NHS ester, its simple isolation, handling, and
      solubility in aqueous buffers, as well as in organic solvents. All these
      features, accompanied by a zero net charge in conjugates, were accomplished by
      the introduction of hydrophilic groups of two types: two hydroxyl groups and one
      sulfonic acid residue.

PMID- 22968961
TI  - Synthesis of porcine pCLCA2 protein during late differentiation of keratinocytes
      of epidermis and hair follicle inner root sheath.
AB  - Despite the discovery of the widely expressed CLCA (chloride channel regulators,
      calcium-activated) proteins more than 15 years ago, their seemingly diverse
      functions are still poorly understood. With the recent generation of porcine
      animal models for cystic fibrosis (CF), members of the porcine CLCA family are
      becoming of interest as possible modulators of the disease in the pig. Here, we
      characterize pCLCA2, the porcine ortholog of the human hCLCA2 and the murine
      mCLCA5, which are the only CLCA members expressed in the skin.
      Immunohistochemical studies with a specific antibody against pCLCA2 have revealed
      a highly restricted pCLCA2 protein expression in the skin. The protein is
      strictly co-localized with filaggrin and trichohyalin in the granular layer of
      the epidermis and the inner root sheath of the hair follicles, respectively. No
      differences have been observed between the expression patterns of wild-type pigs
      and CF transmembrane conductance regulator(-/-) pigs. We speculate that pCLCA2
      plays an as yet undefined role in the structural integrity of the skin or,
      possibly, in specialized functions of the epidermis, including barrier or defense
      mechanisms.

PMID- 22968962
TI  - Dynamic interface imprinting: high-affinity peptide binding sites assembled by
      analyte-induced recruiting of membrane receptors.

PMID- 22968963
TI  - Effects of California chaparral plants on in vitro ruminal fermentation of forage
      and concentrate diet.
AB  - BACKGROUND: The combustible nature of chaparral plants has been attributed to the
      presence of secondary compounds such as phenolic acids, flavonoids and essential
      oils, among others. However, the implication of the antimicrobial properties of
      secondary compounds of chaparral in modulating rumen microbial metabolism has not
      been determined. The effects of 11 chaparral plants on rumen microbial
      fermentation were assessed in an in vitro batch culture fermentation fed a barley
      silage:barley grain-based low concentrate (LC) and high concentrate (HC) diets.
      RESULTS: With LC, gas production [g dry matter (DM) incubated] and DM
      disappearance (DMD) were unaffected by Adenostoma fasciculatum, Ceanothus
      cuneatus, Baccharis pilularis or Eriodictyon californicum, but all plants except
      C. cuneatus decreased (P < 0.05) CH(4) production. With HC diet, all species
      except A. fasciculatum decreased (P < 0.01) total gas produced. Total volatile
      fatty acids (VFA) produced, molar proportions of acetate, propionate and
      butyrate, and the acetate:propionate (A:P) ratio were unaffected by chaparral
      addition to both HC and LC diets. Increased concentrations of A. fasciculatum and
      E. californicum decreased (linear; P < 0.05) fermentability and productions of
      CH(4) and NH(3) -N. CONCLUSION: Among all chaparral species investigated A.
      fasciculatum and E. californicum added as 10% of LC diet showed some potential to
      exert beneficial effects on rumen microbial fermentation.

PMID- 22968964
TI  - Survivor typologies predict medical surveillance participation: the childhood
      cancer survivor study.
AB  - BACKGROUND: Adult survivors of childhood cancer adhere poorly to recommended
      medical surveillance. We sought to identify modifiable factors that contribute to
      non-adherence. METHODS: Latent class analysis categorized survivors (ages 18-52
      years) at risk of cardiac, breast, or bone late sequelae on the basis of their
      health-related concerns, fears, and motivation. These classifications were
      compared at two time points for self-reported adherence to recommended
      echocardiography, mammography, and bone densitometry screening. RESULTS: Three
      classes (worried, collaborative, and self-controlling) characterized survivors in
      each of the three risk groups: cardiac (N=564; Bayesian information criterion
      [BIC] =10,824.66; Lo-Mendell-Rubin parametric likelihood ratio test [LRMLRT] P=
      .002), breast (N=584; BIC=11,779.97; LRMLRT P< .001), and bone (N=613;
      BIC=11,773.56; LMRLRT P= .028). Only 9% of at-risk survivors in the self
      controlling class reported undergoing bone density screening in 2005, compared
      with 17.2% in the collaborative class (P= .034). Thirteen percent of the self
      controlling, 24% of collaborative (P= .025), and 34% of worried (P= .010) classes
      reported undergoing bone densitometry in 2009. Whereas 73% of at-risk survivors
      in the worried class reported having had an echocardiogram in 2009, only 57% of
      the collaborative (P= .040) and 43% of self-controlling (P< .001) classes did. In
      2005 and 2009, respectively, fewer survivors in the self-controlling class (37%
      and 53%) than in the collaborative (51%, P= .038 and 70%, P= .01) and worried
      (58%, P= .002 and 69%, P= .025) classes reported undergoing mammograms.
      CONCLUSIONS: Modifiable intrapersonal characteristics associated with these three
      classes predict self-reported participation in medical surveillance. Continued
      observation and validation of these survivor profiles may inform tailored
      interventions to enhance survivors' screening participation. Copyright (c) 2012
      John Wiley & Sons, Ltd.

PMID- 22968966
TI  - Detection of cytoplasmic nucleophosmin expression by imaging flow cytometry.
AB  - Mutations within the nucleophosmin NPM1 gene occur in approximately one-third of
      cases of acute myeloid leukemia (AML). These mutations result in cytoplasmic
      accumulation of the mutant NPM protein. NPM1 mutations are currently detected by
      molecular methods. Using samples from 37 AML patients, we investigated whether
      imaging flow cytometry could be a viable alternative to this current technique.
      Bone marrow/peripheral blood cells were stained with anti-NPM antibody and DRAQ5
      nuclear stain, and data were acquired on an ImageStream imaging flow cytometer
      (Amnis Corp., Seattle, USA). Using the similarity feature for data analysis, we
      demonstrated that this technique could successfully identify cases of AML with a
      NPM1 mutation based on cytoplasmic NPM protein staining (at similarity threshold
      of 1.1 sensitivity 88% and specificity 90%). Combining data of mean fluorescence
      intensity and % dissimilar staining in a 0-2 scoring system further improved the
      sensitivity (100%). Imaging flow cytometry has the potential to be included as
      part of a standard flow cytometry antibody panel to identify potential NPM1
      mutations as part of diagnosis and minimal residual disease monitoring. Imaging
      flow cytometry is an exciting technology that has many possible applications in
      the diagnosis of hematological malignancies, including the potential to integrate
      modalities.

PMID- 22968967
TI  - Asymmetric hydrogenation of alpha,beta-unsaturated carboxylic esters with chiral
      iridium N,P ligand complexes.
AB  - Enantioselective conjugate reduction of a wide range of alpha,beta-unsaturated
      carboxylic esters was achieved using chiral Ir N,P complexes as hydrogenation
      catalysts. Depending on the substitution pattern of the substrate, different
      ligands perform best. alpha,beta-Unsaturated carboxylic esters substituted at the
      alpha position are less problematic substrates than originally anticipated and in
      some cases alpha-substituted substrates actually reacted with higher
      enantioselectivity than their beta-substituted analogues. The resulting saturated
      esters with a stereogenic center in the alpha or beta position were obtained in
      high enantiomeric purity.

PMID- 22968965
TI  - Baseline disability in activities of daily living predicts dementia risk even
      after controlling for baseline global cognitive ability and depressive symptoms.
AB  - OBJECTIVES: Late-life disability in activities of daily living (ADL) is theorized
      to be driven by underlying cognitive and/or physical impairment, interacting with
      psychological and environmental factors. Although we expect that cognitive
      deficits would explain associations between ADL disability and dementia risk, the
      current study examined ADL as a predictor of future dementia after controlling
      for global cognitive status. METHODS: The population-based Cache County Memory
      Study (N = 3547) assessed individuals in four triennial waves (average age 74.9
      years, years of education 13.36 years; 57.9% were women). Cox proportional
      hazards regression models assessed whether baseline ADL disability (presence of
      2+ Instrumental ADL and/or 1+ Personal ADL) predicted incident dementia after
      controlling for APOE status, gender, age, baseline cognitive ability (Modified
      Mini-mental State Exam, 3MS-R; adjusted for education level), and baseline
      depressive symptoms (Diagnostic Interview Schedule). RESULTS: Over the course of
      study, 571 cases of incident dementia were identified through in-depth cognitive
      assessment, ending in expert consensus diagnosis. Results from Cox models suggest
      that ADL disability is a statistically significant predictor of incident dementia
      (adjusted hazard ratio = 1.83, p < 0.001), even after controlling for covariates.
      CONCLUSIONS: Findings suggest that ADL disability offers unique contributions in
      risk for incident dementia, even after controlling for global cognitive status.
      We discuss how physical impairment and executive function may play important
      roles in this relationship, and how ADL is useful, not just a diagnostic tool at,
      or after dementia onset, but also as a risk factor for future dementia, even in
      individuals not impaired on global cognitive tests.

PMID- 22968968
TI  - Hysteretic three-step spin crossover in a thermo- and photochromic 3D pillared
      Hofmann-type metal-organic framework.

PMID- 22968970
TI  - Probing temperature-driven flow lines in a gated two-dimensional electron gas
      with tunable spin-splitting.
AB  - We study the temperature flow of conductivities in a gated GaAs two-dimensional
      electron gas (2DEG) containing self-assembled InAs dots and compare the results
      with recent theoretical predictions. By changing the gate voltage, we are able to
      tune the 2DEG density and thus vary disorder and spin-splitting. Data for both
      the spin-resolved and spin-degenerate phase transitions are presented, the former
      collapsing to the latter with decreasing gate voltage and/or decreasing spin
      splitting. The experimental results support a recent theory, based on modular
      symmetry, which predicts how the critical Hall conductivity varies with spin
      splitting.

PMID- 22968969
TI  - Occupational exposures and mortality from cardiovascular disease among women
      textile workers in Shanghai, China.
AB  - BACKGROUND: Exposure to textile fiber dusts, like particulate air pollution, may
      be associated with cardiovascular disease (CVD) mortality. Bacterial endotoxin, a
      potent inflammagen found in cotton dust, may be a specific risk factor. METHODS:
      Female textile workers (N = 267,400) in Shanghai, China were followed for CVD
      mortality (1989-2000). Factory exposures were approximated by sector
      classifications based on materials and processes. Quantitative endotoxin and
      cotton dust measures were available for a subcohort (n = 3,188). Cox proportional
      hazards modeling was used to estimate hazard ratios (HR) and 95% confidence
      interval (CI). RESULTS: Slightly elevated mortality risk for the cotton sector
      was seen for ischemic stroke (HR = 1.12, 95% CI: 0.97-1.31) and hemorrhagic
      stroke (HR = 1.12, 95% CI: 1.02-1.23). Similar hemorrhagic stroke mortality risk
      was observed in high dust sectors (HR = 1.12, 95% CI: 1.02-1.24). No association
      was observed for ischemic heart disease. CONCLUSIONS: Exposures in textile
      factories may have contributed to CVD mortality among this cohort. The specific
      components of these exposures that may be harmful are not clear and should be
      further investigated.

PMID- 22968971
TI  - Review of intravenous immunoglobulin replacement therapy trials for primary
      humoral immunodeficiency patients.
AB  - An available supply of intravenous immunoglobulin (IVIG) is essential for
      individuals with primary humoral immunodeficiency. A shortage in 1997 prompted
      the Food and Drug Administration (FDA) to revise guidelines for the licensure,
      production, and distribution of new IVIG products, including the standardization
      of United States clinical trials regarding endpoints for safety, efficacy, and
      pharmacokinetics. The following review is intended to present current information
      and results of clinical trials in patients with primary immunodeficiency treated
      with IVIG products currently licensed or awaiting licensure in the United States.
      The data presented are compiled from published clinical trials and prescribing
      information generated by manufacturers.

PMID- 22968972
TI  - Rotation-locked 2,6-pyrido-allenophanes: characterization of all stereoisomers.
AB  - New 2,6-disubstituted pyrido-allenophanes with locked rotation of aromatic
      spacers were designed and synthesized. The synthesis was accomplished by Pd
      catalyzed C(sp(2))-C(sp) Sonogashira cross-coupling reaction between 1,3
      diethynylallene (DEA) and 2,6-dibromopyridine followed by an intermolecular ring
      closure. Because racemic DEA was employed, pyrido-allenophanes were obtained as
      mixtures of stereoisomers that were resolved by preparative HPLC. The
      conformational space of all these diastereoisomers was explored at the CAM
      B3LYP/6-31+G*//AM1 level of theory. The isomers were characterized through their
      symmetry properties revealed in NMR, circular dichroism, and chiral stationary
      phase HPLC experiments. X-ray diffraction was used to assign and to corroborate
      the configuration of several diastereoisomers. The unexpected encapsulation of
      two molecules of CHCl(3) in the crystal structures shows the potential of these
      conformationally hampered allenophanes as encapsulating hosts.

PMID- 22968973
TI  - Significant differences in coeliac immunotoxicity of barley varieties.
AB  - SCOPE: The only treatment available for coeliac disease (CD) is a strict diet in
      which the intake of wheat, barley, rye, or oats is avoided. Barley is a major
      cereal crop, grown mainly for its use in brewing, and it has high nutritional
      value. The identification of varieties with a reduced toxicity profile may
      contribute to improve the diet, the quality of life and health of CD patients.
      METHODS AND RESULTS: Searching for harmless barleys, we investigated accessions
      of malting and wild barley, used for developing new cultivated cereals. The CD
      toxicity profile of barleys was screened using G12 antibody and cell
      proliferation and IFN-gamma release from peripheral blood mononuclear cells and
      intestinal biopsies from CD patients. We found a direct correlation between the
      reactivity with G12 and the immunogenicity of the different barleys. CONCLUSION:
      The malting barleys were less immunogenic, with reduced levels of toxic gluten,
      and were possibly less harmful to CD patients. Our findings could raise the
      prospect of breeding barley species with low levels of harmful gluten, and the
      attractive goal of developing nontoxic barley cultivars, always taking into
      account the Codex standard for foods for special dietary use for persons
      intolerant to gluten.

PMID- 22968974
TI  - A general and efficient palladium-catalyzed carbonylative synthesis of 2
      aryloxazolines and 2-aryloxazines from aryl bromides.
AB  - Oxazoline is OK! A general and efficient method for the synthesis of oxazolines
      has been developed. This allowed the preparation of 27 five-membered-ring
      heterocycles and 11 six-membered-ring heterocycles in moderate to good yields.

PMID- 22968975
TI  - 4D visualization of a cathode catalyst layer in a polymer electrolyte fuel cell
      by 3D laminography-XAFS.

PMID- 22968976
TI  - Experimental documentation of the structural consequences of hydrogen-bonding
      interactions to the proximal cysteine of a cytochrome P450.

PMID- 22968977
TI  - Nutritional content of fresh and canned peaches.
AB  - BACKGROUND: The objective of this study was to assess whether canned peaches
      could deliver nutrient levels comparable to fresh peaches. Fresh freestone
      peaches, fresh cling peaches and canned cling peaches were analyzed for vitamins
      A, C and E, folate, antioxidants, total phenolics and total carotenoids to assess
      how these nutrients were affected by the canning process and whether storage
      further changed these components. RESULTS: The vitamins and phytochemicals
      measured in this study were found to be present in canned cling peaches versus
      fresh freestone at statistically significantly higher levels (vitamin C,
      antioxidants and folate); higher but not statistically different levels (vitamin
      A); or lower, but not statistically different levels (vitamin E, total phenolics
      and total carotenoids). There were no statistically significant changes in
      nutrient content during storage for 3 months. CONCLUSIONS: The nutritional
      content of canned peaches has been shown in this study to be comparable to that
      of fresh peaches. There were no statistically significant decreases in those
      nutritional parameters measured in this study between fresh freestone peaches and
      canned cling peaches. Vitamins A and E along with total carotenoids decrease
      immediately upon processing, but appear to stabilize after the processing step,
      showing minimal additional changes upon storage for 3 months. This study shows
      that canned peaches can provide comparable nutrient levels to the consumer as
      fresh peaches, meaning that consumers can enjoy peaches year round without
      worrying about loss of nutrients in their diet.

PMID- 22968978
TI  - QT dispersion in mild cognitive impairment: a possible tool for predicting the
      risk of progression to dementia?
AB  - OBJECTIVE: The aim of this research was to investigate relationships between
      cognitive function and non-invasive, repeatable cardiac parameters in elderly
      subjects suffering from mild cognitive impairment (MCI) or Alzheimer's disease
      (AD). METHODS: Two hundred and twenty-four community-living elderly subjects, 31
      AD patients, 77 MCI patients, and 116 cognitively normal subjects (CNS), were
      evaluated for cognitive abilities (Mini Mental State Examination score (MMSE))
      and for electrocardiographic [corrected heart rate QT interval dispersion (QTcD)]
      and echocardiographic [Left ventricular ejection fraction (LVEF)] parameters.
      RESULTS: Mean values of LVEF were not significantly different between the three
      groups; QTcD mean values were significantly lower in CNS group than in subjects
      with MCI and AD. The Pearson Product Moment Correlation test, carried out in the
      three study groups, showed a significant inverse correlation between QTcD and
      MMSE score (r = -0.357; p < 0.01) in the group of MCI patients, only. In
      multivariable-adjusted linear regression tests, QTcD (p = 0.030) and education (p
      = 0.021) are associated with MMSE score in MCI group. Only the parameter of
      education appears to predict MMSE in CNS group; none of these parameters appear
      to predict MMSE in the group of patients with AD. CONCLUSION: The association
      between QTcD and MMSE requires cautious interpretation and further extensive
      investigation. However, if confirmed by longitudinal studies, the finding could
      play a role in the management of the subjects with MCI.

PMID- 22968980
TI  - [The dark side of summer].

PMID- 22968981
TI  - [Therapy of trauma-induced coagulopathy - what is the evidence?].
AB  - The increasing understanding of trauma-induced coagulopathy has led to an
      expansion of treatment strategies in the acute management of trauma patients. The
      aim of this manuscript is to give a summary of current recommendations for the
      treatment of trauma-induced coagulopathy based on current literature and valid
      guidelines. Thetrauma-induced coagulopathyis an independentacutemultifactorial
      diseasewith significantimpact on the mortalityof severelyinjured patients.
      Largely responsible for the occurrence and severity of trauma-induced
      coagulopathy seems to be tissue trauma and shock-induced hypoperfusion.
      Coagulopathy is amplified by accompanying factors such as hypothermia or
      dilution. Diagnosis and therapy of deranged coagulation should start as soon as
      possible. Routinely tested coagulation parameters are of limited use to confirm
      diagnosis. Therapy follows the concept of "damage control resuscitation".
      Infusion of large volumes should be avoided and a mean arterial pressure of
      65mmHg (in consideration of contraindications!) may be aimed.A specific protocol
      for massive transfusion should be introduced and continued.Acidaemia should be
      prevented and treated by appropriate shock therapy.Loss of body temperature
      should be prevented and treated. Hypocalcaemia <0.9 mmol/l should be avoided and
      may be treated. For actively bleeding patients, packed red blood cells (pRBC) may
      be given at haemoglobin<10g/dl(0,62mmol/l). If massive transfusion is performed
      using fresh frozen plasma (FFP), a ratio of FFP to pRBC of 1:2 to 1:1 should be
      achieved.For treatment of hyperfibrinolysis after severe trauma the use of
      tranexamic acid should be considered at an early stage. Fibrinogen should be
      substituted at levels <1,5g/l (4,41MUmol/l). Prothrombin complex concentrates may
      be helpfull for treatment of diffuse bleeding or anticoagulativemedikation. In
      acute bleeding, platelets may be transfused at a platet count <100000/MUl. For
      diffuse bleeding or thrombocytopathic patients desmopressin might be a
      therapeutic option.If a factor XIII (FXIII) measurement is not promptly
      available, a factor XIII blind-dose should be considered in severe ongoing
      bleeding. The use of recombinant activated coagulation factor VII (rFVIIa) be
      considered if major bleeding persists despite standard attempts to control
      bleeding and best practice use of blood components.

PMID- 22968979
TI  - Validation of a field technique and characterization of fecal glucocorticoid
      metabolite analysis in wild chimpanzees (Pan troglodytes).
AB  - Monitoring adrenocortical activity in wild primate populations is critical, given
      the well-documented relationship between stress, health, and reproduction.
      Although many primate studies have quantified fecal glucocorticoid metabolite
      (FGM) concentrations, it is imperative that researchers validate their method for
      each species. Here, we describe and validate a technique for field extraction and
      storage of FGMs in wild chimpanzees (Pan troglodytes). Our method circumvents
      many of the logistical challenges associated with field studies while yielding
      similar results to a commonly used laboratory method. We further validate that
      our method accurately reflects stress physiology using an adrenocorticotropic
      hormone challenge in a captive chimpanzee and an FGM peak at parturition in a
      wild subject. Finally, we quantify circadian patterns for FGMs for the first time
      in this species. Understanding these patterns may allow researchers to directly
      link specific events with the stress response.

PMID- 22968982
TI  - [Surgical therapy and critical care medicine in severely burned patients - Part
      1: the first 24 ours].
AB  - Critical care medicine in severely burned patients should be adapted to the
      different pathophysiological phases. Accordingly, surgical and non-surgical
      therapy must be coordinated adequately. Initial wound care comprises topical
      treatment of less severely injured skin and surgical debridement of severely
      burned areas. The first 24 hours of intensive care are focused on calculated
      fluid delivery to provide stable hemodynamics and avoid progression of local
      edema formation. In the further course wound treatment with split-thickness skin
      grafts is the major aim of surgical therapy. Critical care is focused on the
      avoidance of complications like infections and ventilator associated lung injury.
      Therefore, lung-protective ventilation strategies, weaning and sedation
      protocols, and early enteral nutrition are important cornerstones of the
      treatment.

PMID- 22968983
TI  - [Obesity in prehospital emergency care].
AB  - The prevalence of obesity has increased steadily in recent years. Obese people
      often suffer from diseases which acute decompensation requires a prompt
      prehospital therapy. The Emergency Medical Service will be confronted with
      difficulties in clinical diagnostic, therapy and especially with a delayed
      management of rescue and transport. It is most important to avoid prehospital
      depreciation in quality and time management. This article reviews the specific
      requirements of prehospital care of obese persons and discusses possible
      solutions to optimize the prehospital therapy.

PMID- 22968984
TI  - [Hospital hygiene - transport of patients with multi-resistant pathogens].
AB  - An ever occurring problem in the health-care services is the handling of patients
      who are carriers of multi-resistant pathogens (MRP). As a general rule, these
      patients must be isolated. Thus, the transport of these patients not only within
      but also outside of the hospital can be a problem. It is not just a matter of
      making the necessary transport of the afflicted patient, e.g., to examination
      suites or operating rooms, possible but also above all of protecting other
      patients and personnel from transmission and potential infection with the
      pathogen. As a rule, the measures of "standard hygiene" are sufficient for an
      adequate protection of patients and personnel. Above all, hand disinfection is of
      decisive importance.

PMID- 22968985
TI  - [Pain in thoracic surgery - pathophysiology and treatment options].

PMID- 22968986
TI  - [Pathophysiology and epidemiology of pain in thoracic surgery].
AB  - Acute and chronic pain are significant problems after thoracic surgery with a
      multifactorial pathogenesis. On the one hand iatrogenic procedures as surgical
      access and complexity of treatment procedures, and on the other hand
      constitutional factors as psychosocial comorbidities affect individual pain
      threshold and the development of a Postthoracic Pain Syndrome (PTPS). Special
      phenomena associated with thoracic surgery like ipsitateral shoulder pain and
      neuropathic pain are discussed. The characterization of pathophysiological
      pathways wants to point out treatment options. In conclusion there is a need for
      well organized, multimodal pain therapy concepts to minimize the risk of
      perioperative and chronic pain.

PMID- 22968987
TI  - [Systemic and regional analgesia in patients undergoing major thoracic surgery].
AB  - Effective, aggressive treatment of pain accompanied with thoracic surgery is
      important and beneficial for patients, since severe postoperative pulmonary
      complications and long-term pain will be reduced. In this systematic issue
      evidence-based strategies in preventing and treating pain after thoracic surgery
      will be reviewed.

PMID- 22968988
TI  - Ultrathin Ca-PO4-CO3 solid-solution nanowires: a controllable synthesis and full
      color emission by rare-earth doping.
AB  - It was found that calcium carbonate (CaCO(3)) and hydroxyapatite
      (Ca(10)(OH)(2)(PO(4))(6)), which are two crucial constituents of the most
      abundant minerals in nature and very important bioinorganic components in the
      tissues of mineralizing organisms, can form solid solutions in a wide range of
      PO(4)(3-)/CO(3)(2-) (P/C) ratios at low temperature when prepared as ultrathin
      nanowire structures. This is due to the special reactivity of ultrasmall
      nanocrystals, which can effectively lower the synthetic temperature and promote
      the formation of solid solutions. The as-prepared ultrathin nanowires with
      suitable P/C ratios presented strong blue luminescence due to the existence of
      abundant defects strengthened by CO(3)(2-). If used as the matrix, the as
      prepared ultrathin nanowires demonstrated bright green or red luminescent
      properties when doped with Tb(3+) or Eu(3+) ions, and simultaneously retained
      their original morphologies. These three kinds of fluorescent nanowires could
      reproduce a full range of luminescence colors based on additive color mixtures of
      the three primary colors (red, green, and blue). In addition, under the same
      reaction system, ultrafine rare-earth-doped (Ce(3+), Tb(3+), Eu(3+)) nanowires
      (about 1 nm in diameter) were synthesized by using a one-step hydrothermal
      process, which further pushed the size of the Ca-PO(4)-CO(3) nanobuilding blocks
      to one unit cell region. These ultrafine nanowires displayed excellent film
      forming properties and the ability to absorb UV radiation.

PMID- 22968989
TI  - Jak/Stat3 signaling promotes somatic cell reprogramming by epigenetic regulation.
AB  - Although leukemia inhibitory factor (LIF) maintains the ground state pluripotency
      of mouse embryonic stem cells and induced pluripotent stem cells (iPSCs) by
      activating the Janus kinase/signal transducer and activator of transcription 3
      (Jak/Stat3) pathway, the mechanism remained unclear. Stat3 has only been shown to
      promote complete reprogramming of epiblast and neural stem cells and partially
      reprogrammed cells (pre-iPSCs). We investigated if and how Jak/Stat3 activation
      promotes reprogramming of terminally differentiated mouse embryonic fibroblasts
      (MEFs). We demonstrated that activated Stat3 not only promotes but also is
      essential for the pluripotency establishment of MEFs during reprogramming. We
      further demonstrated that during this process, inhibiting Jak/Stat3 activity
      blocks demethylation of Oct4 and Nanog regulatory elements in induced cells,
      which are marked by suppressed endogenous pluripotent gene expression. These are
      correlated with the significant upregulation of DNA methyltransferase (Dnmt) 1
      and histone deacetylases (HDACs) expression as well as the increased expression
      of lysine-specific histone demethylase 2 and methyl CpG binding protein 2.
      Inhibiting Jak/Stat3 also blocks the expression of Dnmt3L, which is correlated
      with the failure of retroviral transgene silencing. Furthermore, Dnmt or HDAC
      inhibitor but not overexpression of Nanog significantly rescues the reprogramming
      arrested by Jak/Stat3 inhibition or LIF deprivation. Finally, we demonstrated
      that LIF/Stat3 signal also represents the prerequisite for complete reprogramming
      of pre-iPSCs. We conclude that Jak/Stat3 activity plays a fundamental role to
      promote pluripotency establishment at the epigenetic level, by facilitating DNA
      demethylation/de novo methylation, and open-chromatin formation during late-stage
      reprogramming.

PMID- 22968990
TI  - Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of
      fatty acid-binding protein 7 in mice fed a high-fat diet.
AB  - SCOPE: Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder
      characterized by hepatic fat accumulation and abnormal lipid metabolism. Here, we
      investigated the protective effect of lycopene on high-fat diet-induced hepatic
      steatosis and fatty acid-induced intracellular lipid accumulation by miRNA
      regulation. METHODS AND RESULTS: C57BL/6J mice were fed high-fat diet with or
      without 0.05% lycopene for 8 weeks. Hepa 1-6 cells were treated with stearic acid
      (SA) after 24 h pretreatment with lycopene. Treatment of lycopene improved
      hepatic steatosis in high-fat-fed mice and reduced intracellular lipid
      accumulation induced by SA in Hepa 1-6 cells. We demonstrated that miR-21
      expression was decreased in livers from high-fat diet-fed mice and Hepa 1-6 cells
      treated with SA. Lycopene normalized the downregulation of miR-21, which led to
      the downregulation of fatty acid-binding protein 7 (FABP7), a direct target of
      miR-21, at both the transcriptional and translational levels. This specific
      negative regulation of miR-21 was achieved by targeting the FABP7 3'UTR.
      Upregulation of miR-21 markedly blocked SA-induced intracellular lipid
      accumulation by blocking FABP7 expression. Moreover, silencing of FABP7 reduced
      SA-evoked lipid accumulation in Hepa 1-6 cells. CONCLUSION: The results suggest
      that lycopene may be a useful functional compound for treating NAFLD by
      regulating hepatic lipid metabolism.

PMID- 22968991
TI  - Toward efficient asymmetric carbon-carbon bond formation: continuous flow with
      chiral heterogeneous catalysts.
AB  - A chiral Ca catalyst based on CaCl(2)  with a chiral ligand was developed and
      applied to the asymmetric 1,4-addition of 1,3-dicarbonyl compounds to
      nitroalkenes as a model system. To address product inhibition issues, the Ca
      catalyst was applied to continuous flow with a chiral heterogeneous catalyst. The
      continuous flow system using a newly synthesized, polymer-supported Pybox was
      successfully employed, and the TON was improved 25-fold compared with those of
      the previous Ca(OR)(2)  catalysts.

PMID- 22968992
TI  - Structures and reactivities of O-methylated Breslow intermediates.

PMID- 22968993
TI  - Synthesis of Pd-Rh core-frame concave nanocubes and their conversion to Rh cubic
      nanoframes by selective etching of the Pd cores.

PMID- 22968994
TI  - Limited conformational flexibility in the paratope may be responsible for
      degenerate specificity of HIV epitope recognition.
AB  - Exquisite specificity is the hallmark of antigen-antibody recognition. However,
      breakdown in the specific recognition potential culminating in the binding to
      multiple antigens by a single antibody has been observed, even after the
      maturation of the humoral response. While such a broad specificity may be
      expected to assist the host to counter the antigenic variations associated with
      an immune-evading pathogen, escape from immune surveillance by subtle epitopic
      mutations in pathogens like HIV and influenza virus has been clearly established.
      In the light of this dichotomy, the issues of degeneracy/specificity in the
      humoral response against such epitopes were analysed using three HIV-neutralizing
      epitopes and their variants as a model system. Cross-reactivity was observed in
      the polyclonal response against two of the epitopes. Multi-reactive mAb KEL10 was
      isolated against one of the epitopes, ELDKWA from this response. It is evident
      that even after the affinity maturation, antibodies showing binding to multiple
      variants of an immunizing peptide epitope existed. Binding kinetics and in silico
      structural analyses indicated that conserved interactions across epitopes and
      limited conformational flexibility in the paratope may account for the observed
      multi-reactivity. Though the affinity maturation process is expected to
      incorporate an extent of specificity to the paratope, there appear to be still
      some B-cell clones producing antibodies with subtle flexibility in their binding
      site, as demonstrated in case of KEL10. Generation of such antibodies against
      effective immunogens could be a possible approach for countering the antibody
      neutralization escape by various immune-evading pathogens.

PMID- 22968995
TI  - The bovine CD1D gene has an unusual gene structure and is expressed but cannot
      present alpha-galactosylceramide with a C26 fatty acid.
AB  - Although CD1d and NKT cells have been proposed to have highly conserved functions
      in mammals, data on functions of CD1d and NKT cells in species other than humans
      and rodents are lacking. Upon stimulation with the CD1d-presented synthetic
      antigen alpha-galactosylceramide, human and rodent type I invariant NKT cells
      release large amounts of cytokines. The two bovine CD1D (boCD1D) genes have
      structural features that suggest that they cannot be translated into functional
      proteins expressed on the cell surface. Here we provide evidence that despite an
      intron-exon structure and signal peptide that are different from all other known
      CD1 genes, boCD1D can be translated into a protein that is expressed on the cell
      surface. However, in vivo treatment of cattle (Bos taurus) with 0.1, 1, or 10 ug
      kg-1 of the most commonly used alpha-galactosylceramide, which has a C26 fatty
      acid, did not lead to an increase in body temperature and serum cytokine levels
      of the animals. This lack of reactivity is not due to a complete inability of
      boCD1d to present glycosphingolipids because alpha-galactosylceramide variants
      with shorter fatty acids could be presented by boCD1d to human NKT cells in
      vitro. This suggests that the natural ligands of boCD1d are smaller lipids.

PMID- 22968997
TI  - Depressive symptoms and associated factors in an older Spanish population
      positively screened for disability.
AB  - OBJECTIVES: To measure the prevalence of depressive symptoms and its association
      with a comprehensive set of variables and to study the potential modifying
      effects of sex and age. METHODS: In a cross-sectional study, subjects who tested
      positive to the 12-item World Health Organization disability screening tool were
      selected from a probabilistic sample of persons aged 65 years or older in a rural
      area of Spain. Measurements included EURO-D depression scale, socio-demographics,
      habits, anthropometrics, medical history, cognition, disability, functional
      dependence, self-rated health and pain. Logistic regression models were used to
      obtain adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for the
      association between depression and variables. The modifying effects of age and
      sex were assessed. RESULTS: Prevalence (95% CI) of current depressive symptoms
      among the 438 participants was 35.8% (31.3-40.3%). Depressive symptomatology was
      higher among women (aOR = 2.98). An inverse association was observed with alcohol
      (aORs of 0.52 and 0.27 for consumption of 1-2 and >2 standard units/day,
      respectively, versus abstainers). Depressive symptomatology was associated with
      heart failure (aOR = 4.24), urinary incontinence (aOR = 2.68), ischemic heart
      disease (aOR = 1.87), poor self-rated health and pain. Sex and age modified the
      effect of several variables. CONCLUSION: Prevalence of depressive symptoms,
      albeit high, was less than expected. The consistently strong negative association
      between depressive symptoms and alcohol consumption warrants further in-depth
      research. Awareness of effect modification by key variables, such as sex and age,
      may enable the probability of suffering depression to be more accurately
      assessed, with a view to performing a potential diagnostic work-up.

PMID- 22968996
TI  - The role of dendritic cells in the generation of CD4(+) CD25(HI) Foxp3(+) T cells
      induced by amino acid copolymers.
AB  - The effects of the amino acid copolymers used in the therapy of experimental
      autoimmune encephalomyelitis, poly(Y,E,A,K)(n) (Copaxone((r))) and
      poly(Y,F,A,K)(n), on murine myeloid cells have been investigated. After
      administration of these copolymers to mice, increases in several splenic myeloid
      cell populations were observed, including CD11b(+) CD11c(+) dendritic cells. The
      latter were the major splenic cell type that secreted CCL22 (macrophage-derived
      chemokine) on stimulation with amino acid copolymers. CCL22 secretion was also
      stimulated from bone marrow-derived dendritic cells (BMDC) generated with GM-CSF
      in much larger amounts than from bone marrow-derived macrophages generated with M
      CSF. Moreover, CCL22 secretion could also be obtained using BMDC generated from
      two different types of MHC II(-/-) mice, indicating that an innate immune
      receptor is involved. Finally, incubation of these BMDC or splenic dendritic
      cells with naive CD4(+) CD25(-) T cells resulted in formation of CD4(+) CD25(HI)
      Foxp3 T cells (~25% of which were Foxp3(+)). The number of these regulatory cells
      was doubled by pretreatment of BMDC with amino acid copolymers.

PMID- 22968998
TI  - High-performance liquid chromatographic phenolic compound fingerprint for
      authenticity assessment of honey.
AB  - BACKGROUND: Phenolic compound profiles of 20 honeys of different botanical origin
      (eucalyptus, citrus, chestnut and linden) were obtained by high-performance
      liquid chromatography with ultraviolet detection after solid phase extraction, in
      order to evaluate the effectiveness of the fingerprint method for monofloral
      honey discrimination. RESULTS: A total of 58 peaks were detected at lambda = 280
      nm. Distinctive phenolic compound profiles were obtained in which both the nature
      and the relative amount of the detected compounds were characteristic for
      different botanical source honeys. In order to detect sample groupings,
      chromatographic peak areas were submitted to principal component analysis. Then
      linear discriminant analysis was carried out on the first three principal
      components. In addition, linear discriminant analysis was carried out on the 58
      variables, allowing the selection of five variables able to discriminate honeys
      of different botanical origin. CONCLUSION: The chemometric evaluation of the
      phenolic compound profiles yielded classification models able to group honey
      samples according to their floral source with an excellent degree of agreement.
      The main advantage of the fingerprint approach with respect to traditional
      methods is that it does not require time-consuming identification and
      quantification of the analytes. The method proved to be effective for the
      assessment of honey authenticity.

PMID- 22969000
TI  - A thorough investigation of the active titanium species in TS-1 zeolite by in
      situ UV resonance raman spectroscopy.
AB  - A thorough investigation of the active titanium species in TS-1 zeolite was
      conducted by in situ UV resonance Raman spectroscopy combined with UV/Vis diffuse
      reflectance spectroscopy, DFT calculations, and epoxidation experiments. A new
      titanium species was identified with a characteristic Raman band at 695 cm(-1)
      when excited at the 266 nm laser line. It is shown that the newly found titanium
      species is active in the epoxidation reactions in addition to the tetrahedrally
      coordinated titanium species. However, the acidity of the new titanium species
      could catalyze the ring-opening reactions of the epoxy products. It results in a
      lower selectivity toward the epoxy products relative to that of the tetrahedrally
      coordinated titanium species. The side reaction can be suppressed by the addition
      of a weak basic reagent.

PMID- 22969003
TI  - And yet it rotates: the starter for a molecular Wankel motor.

PMID- 22969002
TI  - One step synthesis of gold-loaded radial mesoporous silica nanospheres and
      supported lipid bilayer functionalization: towards bio-multifunctional sensors.
AB  - A simple synthetic route is developed to achieve gold functionalized radial
      mesoporous silica nanoparticles (Au-MsNP) synthesized by a one step procedure
      fully compatible with basic conditions required for the preparation of
      monodispersed nanospheres. In a second step, Au-MsNP particles have been coated
      with phospholipid bilayers in order to design an advanced biofunctional platform
      with the gold metallic nanoparticles previously grown into the pore channels and
      responsible for a plasmonic activity relevant for biosensing. The size of Au-MsNP
      is checked by dynamic light scattering while zeta potential measurements reflect
      their surface charge. The particle morphology is characterized by transmission
      and scanning electron microscopy and the Si/Au ratios are obtained from energy
      dispersive X-ray analysis. The textural properties of Au-MsNP, specific surface
      area and pore size, are determined from N(2)  adsorption. The supported bilayers
      are achieved from vesicles of different phospholipids incubated with Au-MsNP
      particles. The coating efficiency is investigated by zeta potential and cryo-
      transmission electron microscopy. The plasmonic activities of bare Au-MsNP
      particles and coated lipid bilayer Au-MsNP platform are evidenced for two model
      systems: direct adsorption of bovine serum albumin and molecular recognition
      events between avidin molecules and biotin receptors integrated in the supported
      lipid bilayer.

PMID- 22969001
TI  - Obesity-associated dysregulation of calpastatin and MMP-15 in adipose-derived
      stromal cells results in their enhanced invasion.
AB  - Adipose tissue maintains a subpopulation of cells, referred to as adipose-derived
      stromal/stem cells (ASCs), which have been associated with increased breast
      cancer tumorigenesis and metastasis. For ASCs to affect breast cancer cells, it
      is necessary to delineate how they mobilize and home to cancer cells, which
      requires mobilization and invasion through extracellular matrix barriers. In this
      study, ASCs were separated into four different categories based on the donor's
      obesity status and depot site of origin. ASCs isolated from the subcutaneous
      abdominal adipose tissue of obese patients (Ob(+)Ab(+)) demonstrated increased
      invasion through Matrigel as well as a chick chorioallantoic membrane, a type I
      collagen-rich extracellular matrix barrier. Detailed mRNA and protein analyses
      revealed that calpain-4, calpastatin, and MMP-15 were associated with increased
      invasion, and the silencing of each protease or protease inhibitor confirmed
      their role in ASC invasion. Thus, the data indicate that both the donor's obesity
      status and depot site of origin distinguishes the properties of subcutaneous
      derived ASCs with respect to enhanced invasion and this is associated with the
      dysregulation of calpain-4, calpastatin, and MMP-15.

PMID- 22969004
TI  - Panax ginseng in randomised controlled trials: a systematic review.
AB  - Panax ginseng C.A. Meyer is a common herb with many purported health benefits.
      However, there is no conclusive evidence supporting its use in the treatment of
      any particular disease. We conducted a systematic review to evaluate randomised
      controlled trials. Four English databases were searched with no publication date
      restriction. Included studies evaluated P. ginseng in patients with any type of
      disease or in healthy individuals. We assessed the quality of studies using the
      Cochrane risk of bias tool. Of the 475 potentially relevant studies, 65 met the
      inclusion criteria. These studies examined P. ginseng's effects on psychomotor
      performance (17 studies), physical performance (ten), circulatory system (eight),
      glucose metabolism (six), the respiratory system (five), erectile dysfunction
      (four), immunomodulation (four), quality of life/mood (four), antioxidant
      function (two), cancer (two), menopausal symptoms (two) and dry mouth (one). The
      risk of bias was unclear in most studies. Authors evaluated adverse events in 40
      studies, with 135 minor events and no serious adverse events reported. P. ginseng
      shows promising results for improving glucose metabolism and moderating the
      immune response. This may have implications for several diseases including type 2
      diabetes and chronic respiratory conditions. Further studies are needed to
      explore P. ginseng's potential as an effective treatment for these and other
      health conditions.

PMID- 22969005
TI  - Correlations between the levels of Oct4 and Nanog as a signature for naive
      pluripotency in mouse embryonic stem cells.
AB  - The pluripotent state is traditionally associated with large absolute levels of
      certain transcription factors such as Nanog and Oct4. Here, we present
      experimental observations using quantitative immunofluorescence that pluripotency
      in mouse embryonic stem cells (mESCs) is established by specific ratios between
      Oct4 and Nanog. When cells are grown in 2i conditions, they exhibit uniform
      levels of pluripotency and this is associated with a high correlation between the
      levels of Oct4 and Nanog in individual cells. The correlation is lost when cells
      differentiate. Our results suggest that the correlation between these two factors
      and the distribution of Oct4/Nanog ratios can be used as quantifiers to
      distinguish between three subpopulations in an mESC culture: pluripotent, lineage
      primed, and differentiating cells. When we apply these quantifiers to cells with
      lower levels of Nanog or mutant for beta-Catenin or Tcf3, the results suggest
      that these cells exhibit higher probability of differentiation.

PMID- 22969006
TI  - Directed self-assembly with sub-100 degrees Celsius processing temperature, sub
      10 nanometer resolution, and sub-1 minute assembly time.

PMID- 22969007
TI  - Absorbed-dose estimation and quality attributes of gamma-irradiated fresh
      shiitake mushrooms.
AB  - BACKGROUND: The general use of food irradiation requires reliable identification
      methods as well as extensive quality characterization. Shiitake (Lentinus edodes)
      mushrooms, packed in polystyrene trays and covered with polyvinylchloride film,
      were investigated for dose-dependent identification and quality characterization
      upon gamma irradiation (0, 1, 2, and 3 kGy). RESULTS: Thermoluminescence (TL)
      analysis of separated minerals provided excellent results to characterize the
      irradiated mushrooms. Low-dose re-irradiation (200-600 Gy), medium-dose re
      irradiation (1-3 kGy) and high-dose re-irradiation (2-6 kGy) were performed and
      compared using an additive dose method. An electronic-nose analysis showed a
      difference in the volatile profiles of mushrooms following irradiation. One-kGy
      irradiated mushrooms showed similar or better quality attributes to those of the
      control samples. Scanning electron microscopy revealed the dose-dependent
      degradation in microstructure of mushrooms upon irradiation. CONCLUSION: An
      absorbed dosed estimation was possible using TL analysis in which 1-3 kGy re
      irradiation technique gave most promising results. An E-nose analysis effectively
      distinguished the samples based on irradiation history. The best quality
      attributes were observed at 1 kGy irradiation. However, the drastic effects of
      irradiation were prominent in 2 and 3 kGy-irradiated mushrooms.

PMID- 22969008
TI  - Regioselectivity in the intramolecular Heck reaction of a series of cyclic
      sulfonamides: an experimental and computational study.
AB  - Regioselectivity in the intramolecular Heck reaction of a series of N-sulfonyl
      2,5-dihydro-3-substituted pyrroles was studied. These substrates are unbiased in
      terms of the formed ring size of the new heterocycle. Results indicate that high
      levels of regioselectivity are observed under a range of conditions, and that
      there is an underlying propensity for carbon-carbon bond formation at the most
      hindered end of the alkene. For two examples (3-Me and 3-tBu), DFT calculations
      were performed and indicate that in both cases, the modelled transition state for
      carbopalladation is energetically lower for the experimentally preferred isomer.

PMID- 22969010
TI  - Creation of pure nanodrugs and their anticancer properties.

PMID- 22969011
TI  - Design of cyclic peptides featuring proline predominantly in the cis conformation
      under physiological conditions.
AB  - Turns are secondary-structure elements that are omnipresent in natively folded
      polypeptide chains. A large variety of four-residue beta-turns exist, which
      differ mainly in the backbone dihedral angle values of the two central residues
      i+1 and i+2. The betaVI-type turns are of particular biological interest because
      the i+2 residue is always a proline in the cis conformation and might thus serve
      as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed
      cyclic hexapeptides containing two proline residues that predominantly adopt the
      cis conformation in aqueous solution. NMR data and MD calculations indicated that
      the cyclic peptide sequences c-(-DXaa-Ser-Pro-DXaa-Lys-Pro-) result in highly
      symmetric backbone structures when both prolines are in the cis conformation and
      the D-amino acids are either alanine or phenylalanine residues. Replacement of
      the serine residue either by phosphoserine or by tyrosine compromises this
      symmetry, but further increases the cis conformation content of both prolines. As
      a result, we obtained a cyclic hexapeptide that exists almost exclusively as the
      cis-Pro/cis-Pro conformer but shows no cis/trans interconversion even in the
      presence of the PPIase Pin1, apparently due to an energetically quite favorable
      but highly restricted conformational space.

PMID- 22969012
TI  - In vitro activity of xanthorrhizol isolated from the rhizome of Javanese turmeric
      (Curcuma xanthorrhiza Roxb.) against Candida albicans biofilms.
AB  - The purpose of this study was to investigate the activity of xanthorrhizol
      isolated from Curcuma xanthorrhiza Roxb. on Candida albicans biofilms at
      adherent, intermediate, and mature phase of growth. C. albicans biofilms were
      formed in flat-bottom 96-well microtiter plates. The biofilms of C. albicans at
      different phases of development were exposed to xanthorrhizol at different
      concentrations (0.5 ug/mL-256 ug/mL) for 24 h. The metabolic activity of cells
      within the biofilms was quantified using the XTT reduction assay. Sessile minimum
      inhibitory concentrations (SMICs) were determined at 50% and 80% reduction in the
      biofilm OD490 compared to the control wells. The SMIC50 and SMIC80 of
      xanthorrhizol against 18 C. albicans biofilms were 4--16 ug/mL and 8--32 ug/mL,
      respectively. The results demonstrated that the activity of xanthorrhizol in
      reducing C. albicans biofilms OD490 was dependent on the concentration and the
      phase of growth of biofilm. Xanthorrhizol at concentration of 8 ug/mL completely
      reduced in biofilm referring to XTT-colorimetric readings at adherent phase,
      whereas 32 ug/mL of xanthorrhizol reduced 87.95% and 67.48 % of biofilm referring
      to XTT-colorimetric readings at intermediate and mature phases, respectively.
      Xanthorrhizol displayed potent activity against C. albicans biofilms in vitro and
      therefore might have potential therapeutic implication for biofilm-associated
      candidal infections.

PMID- 22969014
TI  - Tunable dual fluorescence of 3-(2,2'-bipyridyl)-substituted iminocoumarin.
AB  - 3-(2,2'-Bipyridyl)-substituted iminocoumarin molecules (compounds 1 and 2)
      exhibit dual fluorescence. Each molecule has one electron donor and two electron
      acceptors that are in conjugation, which leads to fluorescence from two
      independent charge transfer (CT) states. To account for the dual fluorescence, we
      subscribe to a kinetic model in which both CT states form after rapid decays from
      the directly accessed S(1) and S(2) excited states. Due to the slow internal
      conversion from S(2) to S(1), or more likely the slow interconversion between the
      two subsequently formed CT states, dual emission is allowed to occur. This
      hypothesis is supported by the following evidence: 1) the emission at short and
      long ends of the spectrum originates from two different excitation spectra, which
      eliminates the possibility that dual emission occurs after an adiabatic reaction
      at the S(1) level. 2) The fluorescence quantum yield of compound 2 grows with
      increasing excitation wavelength, which indicates that the high-energy excitation
      elevates the molecule to a weakly emissive state that does not internally convert
      to the low-energy, highly emissive state. The intensity of the two emission bands
      of 1 is tunable through the specific interactions between either of the two
      electron acceptors with another species, such as Zn(2+) in the current
      demonstration. Therefore, the development of ratiometric fluorescent indicators
      based on the dual-emitting iminocoumarin system is conceivable. Further
      fundamental studies on this series of compounds using time-resolved spectroscopic
      techniques, and explorations of their applications will be carried out in the
      near future.

PMID- 22969015
TI  - Determination of intrinsic binding modes by mass spectrometry: gas-phase behavior
      of adamantylated bisimidazolium guests complexed to cucurbiturils.
AB  - Adamantylated bisimidazolium cations exhibit a distinct fragmentation pathway in
      contrast to their cucurbit[7]uril (CB7) complexes. The observed alternative
      fragmentation of the guest molecule in a complex clearly correlates to the
      supposed sterically hindered or allowed slippage of the macrocycle over the axel
      molecule.

PMID- 22969013
TI  - Hes4 controls proliferative properties of neural stem cells during retinal
      ontogenesis.
AB  - The retina of fish and amphibian contains genuine neural stem cells located at
      the most peripheral edge of the ciliary marginal zone (CMZ). However, their cell
      of-origin as well as the mechanisms that sustain their maintenance during
      development are presently unknown. We identified Hes4 (previously named XHairy2),
      a gene encoding a bHLH-O transcriptional repressor, as a stem cell-specific
      marker of the Xenopus CMZ that is positively regulated by the canonical Wnt
      pathway and negatively by Hedgehog signaling. We found that during retinogenesis,
      Hes4 labels a small territory, located first at the pigmented epithelium
      (RPE)/neural retina (NR) border and later in the retinal margin, that likely
      gives rise to adult retinal stem cells. We next addressed whether Hes4 might
      impart this cell subpopulation with retinal stem cell features: inhibited RPE or
      NR differentiation programs, continuous proliferation, and slow cell cycle speed.
      We could indeed show that Hes4 overexpression cell autonomously prevents retinal
      precursor cells from commitment toward retinal fates and maintains them in a
      proliferative state. Besides, our data highlight for the first time that Hes4 may
      also constitute a crucial regulator of cell cycle kinetics. Hes4 gain of function
      indeed significantly slows down cell division, mainly through the lengthening of
      G1 phase. As a whole, we propose that Hes4 maintains particular stemness features
      in a cellular cohort dedicated to constitute the adult retinal stem cell pool, by
      keeping it in an undifferentiated and slowly proliferative state along embryonic
      retinogenesis.

PMID- 22969017
TI  - Elastic and bendable caffeine cocrystals: implications for the design of flexible
      organic materials.

PMID- 22969016
TI  - Protein-protected Au clusters as a new class of nanoscale biosensor for label
      free fluorescence detection of proteases.

PMID- 22969018
TI  - Nondestructive photoluminescence read-out by intramolecular electron transfer in
      a perylene bisimide-diarylethene dyad.
AB  - A novel, highly stable photochromic dyad 3 based on a perylene bisimide (PBI)
      fluorophore and a diarylethene (DAE) photochrome was synthesized and the optical
      and photophysical properties of this dyad were studied in detail by steady-state
      and time-resolved ultrafast spectroscopy. This photochromic dyad can be switched
      reversibly by UV-light irradiation of its ring-open form 3 o leading to the ring
      closed form 3 c, and back reaction of 3 c to 3 o by irradiation with visible
      light. Solvent-dependent fluorescence studies revealed that the emission of ring
      closed form 3 c is drastically quenched in solvents of medium (e.g., chloroform)
      to high (e.g., acetone) polarities, while the emission of the ring-open form 3 o
      is appreciably quenched only in highly polar solvents like DMF. The strong
      fluorescence quenching of 3 c is attributed to a photoinduced electron-transfer
      (PET) process from the excited PBI unit to ring-closed DAE moiety, as this
      process is thermodynamically highly favorable with a Gibbs free energy value of 
      0.34 eV in dichloromethane. The electron-transfer mechanism for the fluorescence
      quenching of ring-closed 3 c is substantiated by ultrafast transient measurements
      in dichloromethane and acetone, revealing stabilization of charge-separated
      states of 3 c in these solvents. Our results reported here show that the new
      photochromic dyad 3 has potential for nondestructive read-out in write/read/erase
      fluorescent memory systems.

PMID- 22969019
TI  - Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell
      proliferation in gastric mucosa during the healing process.
AB  - Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipe
      roxo' and has been used in folk medicine as anti-inflammatory and in the
      treatment of ulcers, bacterial and fungal infections. This study evaluated the
      gastric ulcer healing property of the ethanolic extract (EET) of barks from
      Tabebuia avellanedae and investigated the mechanisms that may underlie this
      effect. Rats were treated with EET (twice a day for 7 days) after induction of
      chronic gastric ulcers by 80% acetic acid. Following treatment, histological and
      immunohistochemical analysis were performed in gastric ulcer tissues. Oral
      administration of EET (100 and 300 mg/kg) significantly reduced the gastric
      lesion induced by acetic acid in 44 and 36%, respectively. Histopathological
      evaluation demonstrated a contraction of gastric ulcer size, increase of mucus
      layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell
      proliferation (proliferating cell nuclear antigen immunohistochemistry) in
      animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET
      significantly accelerates healing of acetic acid induced gastric ulcer in rats
      through increase of mucus content and cell proliferation, indicating a potential
      usefulness for treatment of peptic ulcer diseases.

PMID- 22969020
TI  - Sonographic diagnosis of pulmonary embolism with cardiac arrest without major
      dilation of the right ventricle or direct sign of lower limb venous thrombosis.
AB  - Bedside focused echocardiography diagnosis of massive pulmonary embolism during
      cardiac arrest is mainly based on the detection of a dilated right ventricle,
      while the lack of compressibility of a deep vein of the lower limbs confirms
      diagnosis in doubtful cases. We describe a case of unusual sonographic signs in a
      young woman with cardiac arrest due to massive pulmonary embolism showing
      spontaneous blood echogenicity in the inferior vena cava ("sludge sign") and
      nonmodulated ("flat") Doppler waveform in the left lower limb veins, suggesting
      isolated iliac vein thrombosis.

PMID- 22969022
TI  - Novel statistical methodology for analyzing longitudinal biomarker data.

PMID- 22969023
TI  - The biomarker revolution.

PMID- 22969024
TI  - A discussion of gene-gene and gene-environment interactions and longitudinal
      genetic analysis of complex traits.

PMID- 22969025
TI  - Exposome: time for transformative research.

PMID- 22969026
TI  - Ten years of standardizing proteomic data: a report on the HUPO-PSI Spring
      Workshop: April 12-14th, 2012, San Diego, USA.
AB  - The Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) was
      established in 2002 with the aim of defining community standards for data
      representation in proteomics and facilitating data comparison, exchange and
      verification. Over the last 10 years significant advances have been made, with
      common data standards now published and implemented in the field of both mass
      spectrometry and molecular interactions. The 2012 meeting further advanced this
      work, with the mass spectrometry groups finalising approaches to capturing the
      output from recent developments in the field, such as quantitative proteomics and
      SRM. The molecular interaction group focused on improving the integration of data
      from multiple resources. Both groups united with a guest work track, organized by
      the HUPO Technology/Standards Committee, to formulate proposals for data
      submissions from the HUPO Human Proteome Project and to start an initiative to
      collect standard experimental protocols.

PMID- 22969031
TI  - Stem cell therapy: from bench to bedside.
AB  - Several countries have increased efforts to develop medical countermeasures to
      protect against radiation toxicity due to acts of bioterrorism as well as cancer
      treatment. Both acute radiation injuries and delayed effects such as cutaneous
      effects and impaired wound repair depend, to some extent, on angiogenesis
      deficiency. Vascular damage influences levels of nutrients, oxygen available to
      skin tissue and epithelial cell viability. Consequently, the evolution of
      radiation lesions often becomes uncontrolled and surgery is the final option-
      amputation leading to a disability. Therefore, the development of strategies
      designed to promote healing of radiation injuries is a major therapeutic
      challenge. Adult mesenchymal stem cell therapy has been combined with surgery in
      some cases and not in others and successfully applied in patients with accidental
      radiation injuries. Although research in the field of radiation skin injury
      management has made substantial progress in the past 10 y, several strategies are
      still needed in order to enhance the beneficial effect of stem cell therapy and
      to counteract the deleterious effect of an irradiated tissue environment. This
      review summarises the current and evolving advances concerning basic and
      translational research based on stem cell therapy for the management of
      radiological burns.

PMID- 22969032
TI  - Self-cleaning functional molecular materials.

PMID- 22969034
TI  - Synthesis and optical and redox properties of symmetric and asymmetric BODIPYs.
AB  - Herein, we present the synthetic route and the photophysical, electrochemical as
      well as laser properties of novel red-emitting boron-dipyrromethenes (BODIPYs)
      bearing arylethyne moieties. Such functionality is added along the main axis of
      the chromophore leading to single- and double-substituted derivatives. The
      relationship between the dye structure and the lasing properties is studied in
      detail with the help of the photophysical and electrochemical properties as well
      as quantum mechanical simulations. The asymmetric substitution of the parent dye
      induces inhomogeneities in the charge distribution, which leads to an overall
      loss of the fluorescence capacity, mainly in polar media. Such non-radiative
      deactivation processes can be softened by decreasing the electron-donor ability
      of the substituent or even avoided by symmetrical substitution. Thus, grafting of
      the arylethyne moieties at the longitudinal axis of the indacene core results in
      an effective strategy to develop red-edge BODIPYs with highly efficient and
      photostable laser emission.

PMID- 22969035
TI  - Nondoped deep-blue organic light-emitting diodes with color stability and very
      low efficiency roll-off: solution-processable small-molecule fluorophores by
      phosphine oxide linkage.
AB  - A series of solution-processable small molecules PO1-PO4 were designed and
      synthesized by linking N-phenylnaphthalen-1-amine groups to a phenyl phosphine
      oxide core through a pi-conjugated bridge, and their thermal, photophysical, and
      electrochemical properties were investigated. The phosphine oxide linkage can
      disrupt the conjugation and allows the molecular system to be extended to enable
      solution processability and high glass transition temperatures (159-181  degrees
      C) while preserving the deep-blue emission. The noncoplanar molecular structures
      resulting from the trigonal-pyramidal configuration of the phosphine oxide can
      suppress intermolecular interactions, and thus these compounds exhibit strong
      deep-blue emission both in solution and the solid state with high
      photoluminescent quantum yield (PLQY) of 0.88-0.99 in dilute toluene solution.
      Solution-processed nondoped organic light-emitting diodes featuring PO4 as
      emitter achieve a maximum current efficiency of 2.36 cd A(-1) with CIE
      coordinates of (0.15, 0.11) that are very close to the NTSC blue standard.
      Noticeably, all devices based on these small-molecular fluorescent emitters show
      striking deep-blue electroluminescent color stability and extremely low
      efficiency roll-off.

PMID- 22969033
TI  - The short isoform of NF-YA belongs to the embryonic stem cell transcription
      factor circuitry.
AB  - Totipotency of embryonic stem cells (ESCs) is controlled at the transcriptional
      level by a handful of transcription factors (TFs) that promote stemness and
      prevent differentiation. One of the most enriched DNA elements in promoters and
      enhancers of genes specifically active in ESCs is the CCAAT box, which is
      recognized by NF-Y, a trimer with histone-like subunits--NF-YB/NF--YC--and the
      sequence-specific NF-YA. We show that the levels of the short NF-YA isoform--NF
      YAs--is high in mouse ESCs (mESCs) and drops after differentiation; a dominant
      negative mutant affects expression of important stem cells genes, directly and
      indirectly. Protein transfections of TAT-NF-YAs stimulate growth and compensate
      for withdrawal of leukemia inhibitory factor (LIF) in cell cultures.
      Bioinformatic analysis identifies NF-Y sites as highly enriched in genomic loci
      of stem TFs in ESCs. Specifically, 30%-50% of NANOG peaks have NF-Y sites and
      indeed NF-Y-binding is required for NANOG association to DNA. These data indicate
      that NF-Y belongs to the restricted circle of TFs that govern mESCs, and,
      specifically, that NF-YAs is the active isoform in these cells.

PMID- 22969037
TI  - A pilot study of electrocortical activity in dysfunctional anger: decreased
      frontocortical activation, impaired attention control, and diminished behavioral
      inhibition.
AB  - Dysfunctional anger, though not a primary clinical diagnosis per se, does present
      clinically as a pathological mood for which treatment is sought. Few studies have
      probed the neurocortical correlates of dysfunctional anger or assessed if
      cognitive processes, such as attention, are altered in dysfunctional anger.
      Though dysfunctional and high trait anger appears to be associated with biased
      processing of anger-eliciting information, few studies have examined if
      dysfunctional anger modulates attention more generally. This is a notable gap as
      volitional attention control is associated with effective emotive regulation,
      which is impaired in dysfunctional anger and in associated acts of aggression. In
      this pilot study, we examined performance and electroencephalographic (EEG)
      profiles during a 12-min continuous performance task (CPT) of sustained attention
      in 15 adults with dysfunctional anger (Anger group) and 14 controls (control
      group). The Anger group had fewer hits at the end of the CPT, which correlated
      with decreased frontocortical activation, suggesting decreased engagement of
      frontal circuits when attention is taxed. The Anger group had more false alarms
      overall indicating impaired response inhibition. Increased right cortical
      activation during the initial portion of CPT existed in the Anger group, perhaps
      reflecting greater engagement of frontal circuits (i.e. effort) during initial
      stages of the task compared to controls. Finally, increased overall beta1 power,
      suggesting increased cortical activation, was noted in the Anger group. These EEG
      patterns suggest a hypervigilant state in dysfunctional anger, which may
      interfere with effective attention control and decrease inhibition. Such
      impairments likely extend beyond the laboratory setting, and may associate with
      aggressive acts in real life.

PMID- 22969038
TI  - Diagnostics for repeated measurements in linear mixed effects models.
AB  - Most currently available methods for detecting discordant subjects and
      observations in linear mixed effects model fits adapt existing methods for single
      level regression data. The most common methods are generalizations of deletion
      based approaches, primarily Cook's distance. This article describes the
      limitations of modifications to Cook's distance and local influence, and suggests
      a new nondeletion subject-level method, studentized residual sum of squares
      (TRSS) plots. We also suggest a new observation-level deletion method that
      detects discordant observations as an application of TRSS plots. The proposed
      method provides greater information on repeated measurements by utilizing revised
      residuals and efficiently evaluating the effect of discordant subjects and
      observations on the estimation of parameters including variance components. We
      compare the performance of the proposed methods with current methods by using the
      orthodontic growth data: a longitudinal dataset with 27 subjects each observed
      four times. TRSS plots successfully identified discordant subjects that were
      missed by modified Cook's distance methods and the local influence approach.
      Extensions of TRSS plots are also described.

PMID- 22969036
TI  - Creating a community resource for protein science.
AB  - In addition to being one of the early pioneers in protein crystallography, Carl
      Branden made significant contributions to science education with his elegant and
      beautifully illustrated book Introduction to Protein Structure (Branden and
      Tooze, New York: Garland, 1991). It is truly an honor to receive this award in
      their names. This award and the 40th anniversary of the Protein Data Bank (PDB;
      Berman et al., Structure 2012;20:391-396) have given me an opportunity to reflect
      on the various components that have contributed to building a resource for
      protein science and to try to quantify the impact of having PDB data openly
      available.

PMID- 22969039
TI  - Systematic structure-activity study on potential chaperone lead compounds for
      acid alpha-glucosidase.
AB  - Acid alpha-glucosidase (GAA) is a lysosomal enzyme and a pharmacological target
      for Pompe disease, an inherited lysosomal storage disorder (LSD). An emerging
      treatment for LSDs is the use of pharmacological chaperones, small molecules that
      enhance total cellular activity of the target lysosomal protein. We have
      systematically studied thirteen inhibitors, which provide good lead compounds for
      the development of GAA chaperones. We have verified binding on GAA at low and
      neutral pH, mapping the range of pH during transport to lysosomes. These ligands
      inhibit GAA competitively and reversibly, and a few of the compounds show higher
      molecular stabilisation capacity than would be expected from their binding
      affinity. These molecules also increase lysosomal localisation of GAA variants in
      cells. In order to understand the specific molecular mechanism of the
      interactions, we docked the compounds to a homology model of the human GAA. Three
      factors contribute to the tightness of binding. Firstly, well-positioned hydroxy
      groups are essential to orient the ligand and make the binding specific.
      Secondly, the open nature of the GAA active site allows both large and small
      ligands to bind. The third and most important binding determinant is the positive
      charge on the ligand, which is neutralised by Asp 518 or Asp 616 on GAA. Our
      study creates a firm basis for the design of drugs to treat Pompe disease, as it
      provides a comparable study of the ligand properties. Our analysis suggests a
      useful drug design framework for specific pharmacological chaperones for human
      GAA. 

PMID- 22969040
TI  - Catalyst-controlled chemoselective arylation of 2-aminobenzimidazoles.

PMID- 22969041
TI  - DNA binding, antioxidant activity, and DNA damage protection of chiral
      macrocyclic Mn(III) salen complexes.
AB  - We are reporting the synthesis, characterization, and calf thymus DNA binding
      studies of novel chiral macrocyclic Mn(III) salen complexes S-1, R-1, S-2, and R
      2. These chiral complexes showed ability to bind with DNA, where complex S-1
      exhibits the highest DNA binding constant 1.20 * 10(6) M(-1). All the compounds
      were screened for superoxide and hydroxyl radical scavenging activities; among
      them, complex S-1 exhibited significant activity with IC(50) 1.36 and 2.37 MUM,
      respectively. Further, comet assay was used to evaluate the DNA damage protection
      in white blood cells against the reactive oxygen species wherein complex S-1 was
      found effective in protecting the hydroxyl radicals mediated plasmid and white
      blood cells DNA damage.

PMID- 22969042
TI  - Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells.
AB  - In colorectal cancer (CRC), a subpopulation of tumor cells, called cancer stem
      cell (CSC) fraction, is suggested to be responsible for tumor initiation, growth,
      and metastasis. The search for a reliable marker to identify these CSCs is
      ongoing as current markers, like CD44 and CD133, are more broadly expressed and
      therefore are not highly selective and currently also lack function in CSC
      biology. Here, we analyzed whether the Wnt target Lgr5, which has earlier been
      identified as a marker for murine intestinal stem cells, could potentially serve
      as a functional marker for CSCs. Fluorescence-activated cell sorting-based
      detection of Lgr5, using three newly developed antibodies, on primary colorectal
      tumor cells revealed a clear subpopulation of Epcam+ Lgr5+ cells. Similarly,
      primary CRC-derived spheroid cultures, known to be enriched for CSCs, contain
      high levels of Lgr5+ cells, which decrease upon in vitro differentiation of these
      CSCs. Selection of the Lgr5(high) CRC cells identified the clonogenic fraction in
      vitro as well as the tumorigenic population in vivo. Finally, we confirm that
      Lgr5 expression is dependent on the Wnt pathway and show that Lgr5 overexpression
      induces clonogenic growth. We thus provide evidence that Lgr5 is, next to a
      functional intestinal stem cell marker, a selective marker for human colorectal
      CSCs.

PMID- 22969043
TI  - Efficacy of attract-and-kill devices for the control of Ceratitis capitata.
AB  - BACKGROUND: The control of Ceratitis capitata Wiedemann traditionally has relied
      on chemical control with organophosphate insecticides. The use of many of these
      substances has been banned by new European directives; therefore, the development
      of new control methods is essential to manage this pest. Bait sprays with
      spinosad, mass trapping and lure-and-kill techniques have been the base for new
      integrated pest management programmes. In this study, a 2 year field trial was
      conducted in two citrus areas to test the efficacy of attract-and-kill devices
      against mass trapping and spinosad-plus-bait treatments. RESULTS: The Magnet((r))
      MED attract-and-kill device, Spintor((r)) treatments and mass trapping achieved
      good control of C. capitata populations, as confirmed by low percentages of
      damaged fruit in the assessments performed during the harvest period. On the
      other hand, fly population levels on plots treated with other attract-and-kill
      prototype devices increased more than threefold by comparison with the
      populations recorded in the rest of the treated plots. The same effect was
      observed for fruit damage, with 6-8 times less damage with Magnet((r)) MED and
      spinosad treatments, respectively, than with the attract-and-kill prototype
      devices. CONCLUSION: By using an effective attractant, conventional trapping
      systems can be replaced with cheaper and easier-to-handle attract-and-kill
      devices. The efficacy of these devices and their advantages over conventional
      mass trapping systems are discussed.

PMID- 22969044
TI  - Controlling the regioselectivity of the hydrosilylation reaction in carbon
      nanoreactors.
AB  - Hollow graphitized carbon nanofibres (GNF) are employed as nanoscale reaction
      vessels for the hydrosilylation of alkynes. The effects of confinement in GNF on
      the regioselectivity of addition to triple carbon-carbon bonds are explored. A
      systematic comparison of the catalytic activities of Rh and RhPt nanoparticles
      embedded in a nanoreactor with free-standing and surface-adsorbed nanoparticles
      reveals key mechanisms governing the regioselectivity. Directions of reactions
      inside GNF are largely controlled by the non-covalent interactions between
      reactant molecules and the nanofibre channel. The specific pi-pi interactions
      increase the local concentration of the aromatic reactant and thus promote the
      formation of the E isomer of the beta-addition product. In contrast, the presence
      of aromatic groups on both reactants (silane and alkyne) reverses the effect of
      confinement and favours the formation of the Z isomer due to enhanced
      interactions between aromatic groups in the cis-orientation with the internal
      graphitic step-edges of GNF. The importance of pi-pi interactions is confirmed by
      studying transformations of aliphatic reactants that show no measurable changes
      in regioselectivity upon confinement in carbon nanoreactors.

PMID- 22969045
TI  - Dynamics of Plasmodium falciparum enoyl-ACP reductase and implications on drug
      discovery.
AB  - Enoyl-acyl carrier protein reductase (ENR) is a crucial enzyme in the type II
      fatty acid synthesis pathway of many pathogens such as Plasmodium falciparum, the
      etiological agent of the most severe form of malaria. Because of its essential
      function of fatty acid double bond reduction and the absence of a human
      homologue, PfENR is an interesting drug target. Although extensive knowledge of
      the protein structure has been gathered over the last decade, comparatively
      little remains known about the dynamics of this crucial enzyme. Here, we perform
      extensive molecular dynamics simulations of tetrameric PfENR in different states
      of cofactor and ligand binding, and with a variety of different ligands bound. A
      pocket-volume analysis is also performed, and virtual screening is used to
      identify potential druggable hotspots. The implications of the results for future
      drug-discovery projects are discussed.

PMID- 22969047
TI  - Quinolinium-based fluorescent probes for the detection of thiophenols in
      environmental samples and living cells.
AB  - A new type of fluorescent probes for thiophenols, 6HQM-DNP and 7HQM-DNP,
      containing 6- or 7-hydroxy quinonlinium as fluorophore and 2,4-dinitrophenoxy
      (DNP) as nucleophilic recognition unit were constructed. As ethers, these non
      fluorescent probe molecules can release the corresponding fluorescent quinolinium
      (6HQM and 7HQM) through aromatic nucleophilic substitution (S(N)Ar) by thiolate
      anions from thiophenols. The sensing reaction is highly sensitive (detection
      limit of 8 nM for 7HQM-DNP) and highly selective to thiophenols over aliphatic
      thiols and other nucleophiles under neutral conditions (pH 7.3). The probes
      respond rapidly to thiophenols, with second-order rate constants k=45 M(-1)  s(
      1) for 7HQM-DNP and 24 M(-1)  s(-1) for 6HQM-DNP. Furthermore, the selective
      detection of thiophenols in living cells by 7HQM-DNP was demonstrated by confocal
      fluorescence imaging. In addition, these quinolinium salts show excellent
      chemical and thermal stability. In conclusion, this type of probes may find use
      in the detection of thiophenols in environmental samples and biosystems.

PMID- 22969046
TI  - A template carbonization strategy to synthesize ordered mesoporous silica
      microspheres with trapped sulfonated carbon nanoparticles for efficient
      catalysis.

PMID- 22969048
TI  - Materials research at Rice University.

PMID- 22969050
TI  - The interactions between piperonyl butoxide and E4, a resistance-associated
      esterase from the peach-potato aphid, Myzus persicae Sulzer (Hemiptera:
      Aphididae).
AB  - BACKGROUND: It has been reported previously that piperonyl butoxide (PBO) can
      inhibit both P450 and esterase activity. Although the method by which PBO
      combines with cytochrome P450 has been identified, the way in which it acts as an
      esterase inhibitor has not been established. This paper characterises the
      interactions between PBO and the resistance-associated esterase in Myzus
      persicae, E4. RESULTS: After incubation with PBO/analogues, hydrolysis of 1
      naphthyl acetate by E4 is increased, but sequestration of azamethiphos is
      reduced. Rudimentary in silico modelling suggests PBO docks at the lip of the
      aromatic gorge. CONCLUSIONS: PBO binds with E4 to accelerate small substrates to
      the active-site triad, while acting as a blockade to larger, insecticidal
      molecules. Structure-activity studies with analogues of PBO also reveal the
      essential chemical moieties present in the molecule.

PMID- 22969049
TI  - MHC mismatch results in neural progenitor cell rejection following spinal cord
      transplantation in a model of viral-induced demyelination.
AB  - Transplantation of syngeneic neural progenitor cells (NPCs) into mice
      persistently infected with the JHM strain of mouse hepatitis virus (JHMV) results
      in enhanced differentiation into oligodendrocyte progenitor cells that is
      associated with remyelination, axonal sparing, and clinical improvement. Whether
      allogeneic NPCs are tolerated or induce immune-mediated rejection is
      controversial and poorly defined under neuroinflammatory demyelinating
      conditions. We have used the JHMV-induced demyelination model to evaluate the
      antigenicity of transplanted allogeneic NPCs within the central nervous system
      (CNS) of mice with established immune-mediated demyelination. Cultured NPCs
      constitutively expressed the costimulatory molecules CD80/CD86, and IFN-gamma
      treatment induced expression of MHC class I and II antigens. Injection of
      allogeneic C57BL/6 NPCs (H-2b background) led to a delayed type hypersensitivity
      response in BALB/c (H-2d background) mice associated with T-cell proliferation
      and IFN-gamma secretion following coculture with allogeneic NPCs. Transplantation
      of MHC-mismatched NPCs into JHMV-infected mice resulted in increased transcripts
      encoding the T-cell chemoattractant chemokines CXCL9 and CXCL10 that correlated
      with increased T-cell infiltration that was associated with NPC rejection.
      Treatment of MHC-mismatched mice with T-cell subset-specific depleting antibodies
      increased survival of allogeneic NPCs without affecting commitment to an
      oligodendrocyte lineage. Collectively, these results show that allogeneic NPCs
      are antigenic, and T-cells contribute to rejection following transplantation into
      an inflamed CNS suggesting that immunomodulatory treatments may be necessary to
      prolong survival of allogeneic cells.

PMID- 22969051
TI  - Heat-induced morphological transformation of supramolecular nanostructures by
      retro-Diels-Alder reaction.
AB  - Controlling the morphology of supramolecular nanostructures in response to
      external stimuli is an important challenge in the development of functional soft
      materials. Here we show that a morphological transformation from 2D nanosheets to
      a network of 1D nanofibers is triggered by heating, which induces molecular
      conversion of a bolaamphiphile to a hydrogelator by means of a retro-Diels-Alder
      reaction, thereby producing a new heat-set supramolecular hydrogel. We anticipate
      that our design will be a starting point for more sophisticated supramolecular
      systems that integrate the thermodynamics of molecular assembly and the kinetics
      of chemical reactions to create complex supramolecular nanostructures.

PMID- 22969054
TI  - Benzo[c]thiophene-C60 diadduct: an electron acceptor for p-n junction organic
      solar cells harvesting visible to near-IR light.
AB  - We synthesized a new 56-pi-electron fullerene derivative through a Diels-Alder
      cycloaddition of benzo[c]thiophene that featured a relatively low temperature,
      closer to stoichiometric use of the diene, and easy product purification. The 56
      pi-electron benzo[c]thiophene diadduct (BTCDA) has a LUMO energy level of 0.09 to
      0.18 eV higher than that of 58-pi-electron fullerenes, and therefore, the BTCDA
      based organic photovoltaic device exhibited a higher open-circuit voltage and
      power-conversion efficiency (PCE). When used with a binary-donor system,
      including visible-light-harvesting tetrabenzoporphyrin (BP) and near-IR
      harvesting titanyl phthalocyanine (TiOPc), the device had a PCE that was 1.5-3
      times higher (2.8%) than that for devices with BP or TiOPc alone because the
      binary-donor device can utilize light between lambda=350 and 950 nm.

PMID- 22969053
TI  - Discovery of small-molecule inhibitors of the TLR1/TLR2 complex.

PMID- 22969052
TI  - The enzymes of biotin dependent CO2 metabolism: what structures reveal about
      their reaction mechanisms.
AB  - Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed,
      biotin-dependent enzymes are ubiquitous in nature and are involved in a myriad of
      metabolic processes including fatty acid synthesis and gluconeogenesis. The
      cofactor, itself, is composed of a ureido ring, a tetrahydrothiophene ring, and a
      valeric acid side chain. It is the ureido ring that functions as the CO2 carrier.
      A complete understanding of biotin-dependent enzymes is critically important for
      translational research in light of the fact that some of these enzymes serve as
      targets for anti-obesity agents, antibiotics, and herbicides. Prior to 1990,
      however, there was a dearth of information regarding the molecular architectures
      of biotin-dependent enzymes. In recent years there has been an explosion in the
      number of three-dimensional structures reported for these proteins. Here we
      review our current understanding of the structures and functions of biotin
      dependent enzymes. In addition, we provide a critical analysis of what these
      structures have and have not revealed about biotin-dependent catalysis.

PMID- 22969055
TI  - Novel solution processing of high-efficiency Earth-abundant Cu2 ZnSn(S,Se)4 solar
      cells.
AB  - A novel solution-based approach is presented to process earth-abundant
      Cu(2)ZnSn(S,Se)(4) absorbers using fully dissolved CZTS precursors in which each
      of the elemental constituents intermix on a molecular scale. This method enables
      the low-temperature processing of chemically clean kesterite films with excellent
      homogeneity. The high performance of resulting optoelectronic devices represents
      a chance to extend the impact of CZTS into the next chapter of thin-film solar
      cells.

PMID- 22969056
TI  - Capillary gel electrophoresis for precise protein quantitation.
AB  - CGE, also known as SDS-CGE, is being established in the pharmaceutical industry
      replacing SDS-PAGE. In most cases, the method is applied for the identity and
      purity control of proteins, for example monoclonal antibodies. In order to
      quantify these components with sufficient precision using the same quality
      control method, a RSD for the quantitative analysis under 2% is required. A
      reliable and highly precise CGE method could be obtained after thorough
      optimization. It was crucial to increase the sample concentration and the
      injection volume in order to achieve sufficiently high S/N ratios (>70). The
      application of hydrodynamic injection is beneficial for the precision of the
      method compared to the traditionally used electrokinetic one. Linearity was
      demonstrated and LOD and LOQ were estimated. Both injection modes were compared
      in long series runs (n = 48). Furthermore, the use of an internal standard was
      investigated. Thus, the RSD% of the migration time was reduced from 0.9 to 0.2%
      and the RSD% of peak areas was greatly improved. However, the normalization to
      the total area further reduced the influence of the injection error. RSD% for the
      peak area ratios of typically between 1 and 2% was provided.

PMID- 22969058
TI  - Inflammatory protein expression in adolescent and adult offspring of type 1
      diabetic mice.
AB  - AIMS: To measure inflammatory markers in offspring of pregestational type 1
      diabetic mothers. METHODS: Type 1 diabetes was induced in female C57BL6/J mice
      using streptozotocin. Offspring from control C57BL6/J and type 1 diabetic mothers
      were followed up to adulthood and blood was collected at 6 and 12 weeks of age,
      representing adolescent and adult stages respectively. Five well-established
      inflammatory markers; Matrix metalloproteinase 9, soluble E-selectin, sICAM-1,
      sVCAM-1, and total plasminogen activator inhibitor-1 (PAI-1) were measured on an
      inflammatory multiplex assay in plasma. RESULTS: Blood plasma from adolescent
      offspring from diabetic mothers displayed an increase in all five inflammatory
      markers when compared to controls, and there was a highly significant increase in
      sVCAM-1 (64.56 +/- 20.1 vs. 33.8 +/- 20.75; p < 0.01) and tPAI-1 (0.05 +/- 0.02
      vs. 0.02 +/- 0.01; p < 0.01) expression. CONCLUSION: Our findings show that
      inflammatory markers are increased in offspring of pregestational diabetic
      mothers. This may represent a mechanism for increased risk of cardiovascular
      disease evident in these offspring.

PMID- 22969057
TI  - Primary cilia-mediated mechanotransduction in human mesenchymal stem cells.
AB  - Physical loading is a potent stimulus required to maintain bone homeostasis,
      partly through the renewal and osteogenic differentiation of mesenchymal stem
      cells (MSCs). However, the mechanism by which MSCs sense a biophysical force and
      translate that into a biochemical bone forming response (mechanotransduction)
      remains poorly understood. The primary cilium is a single sensory cellular
      extension, which has recently been shown to demonstrate a role in cellular
      mechanotransduction and MSC lineage commitment. In this study, we present
      evidence that short periods of mechanical stimulation in the form of oscillatory
      fluid flow (OFF) is sufficient to enhance osteogenic gene expression and
      proliferation of human MSCs (hMSCs). Furthermore, we demonstrate that the cilium
      mediates fluid flow mechanotransduction in hMSCs by maintaining OFF-induced
      increases in osteogenic gene expression and, surprisingly, to limit OFF-induced
      increases in proliferation. These data therefore demonstrate a pro-osteogenic
      mechanosensory role for the primary cilium, establishing a novel
      mechanotransduction mechanism in hMSCs. Based on these findings, the application
      of OFF may be a beneficial component of bioreactor-based strategies to form bone
      like tissues suitable for regenerative medicine and also highlights the cilium as
      a potential therapeutic target for efforts to mimic loading with the aim of
      preventing bone loss during diseases such as osteoporosis. Furthermore, this
      study demonstrates a role for the cilium in controlling mechanically mediated
      increases in the proliferation of hMSCs, which parallels proposed models of
      polycystic kidney disease. Unraveling the mechanisms leading to rapid
      proliferation of mechanically stimulated MSCs with defective cilia could provide
      significant insights regarding ciliopathies and cystic diseases.

PMID- 22969059
TI  - From biomass wastes to highly efficient CO2 adsorbents: graphitisation of
      chitosan and alginate biopolymers.
AB  - Carbon spheres from natural biopolymers (alginate and chitosan) are easily
      synthesised by thermal treatment between 400 and 800  degrees C under an inert
      atmosphere. All the samples, including the untreated natural biopolymers, as well
      as the resulting carbon materials, exhibit a remarkable CO2-adsorption capacity.
      The sample that exhibits the highest adsorption capacity was that obtained by
      carbonisation of alginate at 800  degrees C and subsequent treatment with KOH at
      800  degrees C. This material exhibits a specific surface area of 765 m2  g-1,
      specific micropore volume of 0.367 cm3  g-1, ultra-micropore volume of 0.185 cm3 
      g-1, average ultra-micropore size of 0.7 nm and CO2-adsorption capacity of 5 mmol
      g-1 measured at 0  degrees C and atmospheric pressure. This value is close to the
      absolute record for CO2 adsorption and, by far, the highest if we compare unit
      areas or consider the density of the material. The combination of the high N
      content already included in the chitosan structure and the elevated microporosity
      in the case of alginate are crucial factors to obtain these satisfactory values
      with an easy and green preparation procedure. Also, owing to the high
      conductivity of the alginate-derived carbon (better than graphite), it has been
      possible to develop a process of reversible adsorption-desorption by applying a
      voltage, which is a low-energy desorption method compared with the conventional
      method of vacuum and high temperatures. All these properties, together with the
      spherical shape of the material of 0.1 mm, which is the most suitable form to
      favour mass transfer in fluidised-bed reactors, make this material a highly
      promising adsorbent for industrial applications.

PMID- 22969060
TI  - Iridium-catalyzed asymmetric hydrogenation of pyridinium salts.

PMID- 22969061
TI  - Advances in supramolecular electronics - from randomly self-assembled
      nanostructures to addressable self-organized interconnects.
AB  - Supramolecular organic electronics rests on the use of bottom-up chemical self
      assembly processes in order to design conducting components on the 5-100 nm
      scale. The challenges in this field are both the construction of 1D
      nanostructures displaying optimized transport properties and their precise
      connections to electrodes. The present Research News highlights important
      advances in such materials regarding their electrical performances, from
      semiconductors to organic metals, but also regarding their processability. In
      particular, by externally controlling light-responsive supramolecular
      polymerization processes, and by using appropriate methods of casting with an
      applied electric field, it becomes possible to pre-determine the accurate
      positioning of organic interconnects within patterned nano-circuitry. These
      strategies using external stimuli to obtain addressability, thus hold promising
      alternatives to other conducting materials such as carbon nanotubes for further
      technological applications in nanosciences.

PMID- 22969062
TI  - The insect peptide CopA3 inhibits lipopolysaccharide-induced macrophage
      activation.
AB  - We recently demonstrated that the insect peptide CopA3 (LLCIALRKK), a disulfide
      linked dimeric peptide, exerts antimicrobial and anti-inflammatory activities in
      a mouse colitis model. Here, we examined whether CopA3 inhibited activation of
      macrophages by LPS. Exposure of an unseparated mouse peritoneal cell population
      or isolated peritoneal macrophages to LPS markedly increased secretion of IL-6
      and TNF-alpha; these effects were significantly inhibited by CopA3 treatment. The
      inhibitory effect of CopA3 was also evident in murine macrophage cell line, RAW
      264.7. Western blotting revealed that LPS-induced activation of STAT1 and STAT5
      in macrophages was significantly inhibited by CopA3. Inhibition of JAK
      (STAT1/STAT5 kinase) with AG490 markedly reduced the production of IL-6 and TNF
      alpha in macrophages. Collectively, these observations suggest that CopA3
      inhibits macrophage activation by inhibiting activating phosphorylations of the
      transcription factors, STAT1 and STAT5, and blocking subsequent production of IL
      6 and TNF-alpha and indicate that CopA3 may be useful as an immune-modulating
      agent.

PMID- 22969063
TI  - Gallium(III)-catalyzed three-component (4+3) cycloaddition reactions.

PMID- 22969064
TI  - Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of
      gestation and the impact of neonatal Fc receptor (FcRn) binding.
AB  - BACKGROUND: There is concern about embryo-fetal exposure to antibody-based
      biopharmaceuticals based on the increase of such therapies being prescribed to
      women of childbearing potential. Therefore, there is a desire to better
      characterize embryo-fetal exposure of these molecules. The pregnant rat is a
      standard model for evaluating the potential consequences of exposure but
      placental transfer of antibody-based biopharmaceuticals is not well understood in
      this model. METHODS: The relative embryo-fetal distribution of an antibody-based
      biopharmaceutical was evaluated in the rat. Bevacizumab (Avastin) was chosen as a
      tool antibody since it does not have significant target binding in the rat that
      might influence embryo-fetal biodistribution. Avastin was labeled with a
      fluorescent dye, characterized, and injected into pregnant rats at different
      gestation ages. Labeled Avastin in fetal tissues was visualized ex vivo using an
      IVIS 200 (Caliper, A PerkinElmer Company, Alameda, CA). RESULTS: Avastin
      localized to the fetus as early as 24-hr post intravenous injection of the dam,
      and was taken up by the fetus in a dose-dependent manner. Avastin was detectable
      in the developing embryo as early as gestation day 13 and continued to be
      transferred until the end of gestation. Fetal transfer of Avastins mutated in the
      portion of the antibody that binds the neonatal Fc receptor (FcRn) was tested in
      late gestation and was found to correlate with affinities of the mutant Avastin
      antibody to FcRn. CONCLUSIONS: The novel application of this imaging technology
      was used to characterize the onset and duration of Avastin maternal-fetal
      transfer in rats and the importance of FcRn binding.

PMID- 22969065
TI  - An MoS(x) structure with high affinity for adsorbate interaction.

PMID- 22969066
TI  - Phagocytic uptake and ROS-mediated cytotoxicity in human hepatic cell line of
      amphiphilic polyphosphazene nanoparticles.
AB  - The pH-responsive amphiphilic polyphosphazenes bearing N,N
      diisopropylethylenediamine (DPA) have been proven to be promising nanovehicles
      for drug antitumor therapy. To further modify these amphiphilic polyphosphazenes
      with fluorescent labeling agent or other biochemical functional groups, serine
      methyl ester containing active chemical group ?NH(2) was chosen to be introduced
      to get a novel polymer [NP(PEG)(0.24) (DPA)(0.5)(SME)(1.26) (n) (PDS-NH(2) ).
      Considering the possible toxic effect of -NH(2) group, the biocompatibility in
      bloodstream and nanotoxicity on human normal hepatic L-02 cells was evaluated in
      this study. The polymer [NP(PEG)(0.24)(DPA)(0.5)(SME-BOC)(1.26)](n) (PDS-BOC)
      linked with tert-butyloxycarbonyl groups to protect and hide -NH(2) group was
      applied as the comparison. First, the bovine serum albumin (BSA) adsorption and
      phagocytic uptake behavior in human THP-1 macrophages were performed. The results
      suggested that only a minor percentage of the nanoparticles were involved in BSA
      binding and phagocytic uptake as the result of PEGylation on the particulate
      surface. To determine the nanotoxicity on human normal hepatic L-02 cells, we
      measured cell viability, apoptosis and necrosis, reactive oxygen species
      generation, the loss of mitochondrial membrane potential, and the levels of the
      apoptotic signaling proteins in L-02 cells after the cells being exposed to
      nanoparticles of different concentrations (0.1, 0.2, and 0.5 mg/mL) for 24 h. Our
      data indicated that the two nanoparticles induced cytotoxicity in a dose
      dependent manner; PDS-NH(2) caused more cytotoxicity than PDS-BOC as a result of 
      NH(2) exposure. The increased expression of caspase-3 and caspase-9 suggested
      that they triggered apoptosis through mitochondria-dependent pathways in L-02
      cells.

PMID- 22969068
TI  - Retardation of myopia in Orthokeratology (ROMIO) study: a 2-year randomized
      clinical trial.
AB  - PURPOSE: This single-masked randomized clinical trial aimed to evaluate the
      effectiveness of orthokeratology (ortho-k) for myopic control. METHODS: A total
      of 102 eligible subjects, ranging in age from 6 to 10 years, with myopia between
      0.50 and 4.00 diopters (D) and astigmatism not more than 1.25D, were randomly
      assigned to wear ortho-k lenses or single-vision glasses for a period of 2 years.
      Axial length was measured by intraocular lens calculation by a masked examiner
      and was performed at the baseline and every 6 months. This study was registered
      at ClinicalTrials.gov, number NCT00962208. RESULTS: In all, 78 subjects (37 in
      ortho-k group and 41 in control group) completed the study. The average axial
      elongation, at the end of 2 years, were 0.36 +/- 0.24 and 0.63 +/- 0.26 mm in the
      ortho-k and control groups, respectively, and were significantly slower in the
      ortho-k group (P < 0.01). Axial elongation was not correlated with the initial
      myopia (P > 0.54) but was correlated with the initial age of the subjects (P <
      0.001). The percentages of subjects with fast myopic progression (>1.00D per
      year) were 65% and 13% in younger (age range: 7-8 years) and older (age range: 9
      10 years) children, respectively, in the control group and were 20% and 9%,
      respectively, in the ortho-k group. Five subjects discontinued ortho-k treatment
      due to adverse events. CONCLUSIONS: On average, subjects wearing ortho-k lenses
      had a slower increase in axial elongation by 43% compared with that of subjects
      wearing single-vision glasses. Younger children tended to have faster axial
      elongation and may benefit from early ortho-k treatment. (ClinicalTrials.gov
      number, NCT00962208.).

PMID- 22969067
TI  - Genetic variants near PDGFRA are associated with corneal curvature in
      Australians.
AB  - PURPOSE: Irregularity in the corneal curvature (CC) is highly associated with
      various eye disorders such as keratoconus and myopia. The sample had limited
      power to find genomewide significant (5 * 10(-8)) hits but good power for
      replication. Thus, an attempt was made to test whether alleles in the FRAP1 and
      PDGFRA genes, recently found to be associated with CC in Asian populations, also
      influence CC in Australians of North European ancestry. Results of initial
      genomewide association studies (GWAS) for CC in Australians were also reported.
      METHODS: Two population-based cohorts of 1788 Australian twins and their
      families, as well as 1013 individuals from a birth cohort from Western Australia,
      were genotyped using genomewide arrays. Following separate individual analysis
      and quality control, the results from each cohort underwent meta-analysis.
      RESULTS: Meta-analysis revealed significant replication of association between
      rs2114039 and corneal curvature (P = 0.0045). The SNP rs2114039 near PDGFRA has
      been previously implicated in Asians. No SNP at the FRAP1 locus was found to be
      associated in our Australian samples. No SNP surpassed the genomewide
      significance threshold of 5 * 10(-8). The SNP with strongest association was
      rs2444240 (P = 3.658 * 10(-7)), which is 31 kb upstream to the TRIM29 gene.
      CONCLUSIONS: A significant role of the PDGFRA gene in determining corneal
      curvature in the Australian population was confirmed in this study, also
      highlighting the putative association of the TRIM29 locus with CC.

PMID- 22969069
TI  - Macular function in eyes with open-angle glaucoma evaluated by multifocal
      electroretinogram.
AB  - PURPOSE: To evaluate macular function in patients with open-angle glaucoma (OAG)
      by means of multifocal electroretinogram (mfERG). METHODS: Twenty-four OAG
      patients (mean age 54.6 +/- 9.1 years) and 14 age-similar controls were enrolled.
      OAG patients had intraocular pressure (IOP) less than 18 mm Hg with topical
      medical treatment, 24-2 visual field (Humphrey Field Analyzer [HFA]) with mean
      deviation (MD) between -2 and -12 dB, and corrected pattern standard deviation
      (CPSD) between +2 and +10 dB and no history or presence of cataract and/or
      macular disease. MfERGs in response to 61 M-stimuli presented to the central 20
      degrees  of the visual field were assessed in OAG patients (24 eyes) and in
      controls (14 eyes). Ring (R) analysis was performed every five retinal
      eccentricities in areas between the fovea and midperiphery: 0 degrees  to 2.5
      degrees  (R1), 2.5 degrees  to 5 degrees  (R2), 5 degrees  to 10 degrees  (R3),
      10 degrees  to 15 degrees  (R4), and 15 degrees  to 20 degrees  (R5). MfERG
      response amplitude density of the N1-P1 components (N1-P1 RAD, nV/deg(2)) and P1
      implicit time (P1 IT, ms) of the first-order binary kernel were measured for each
      ring. RESULTS: OAG patients showed a significant (P < 0.01) decrease in N1-P1
      RADs and an increase in P1 IT in both R1 and R2 with respect to controls. The
      reduction in N1-P1 RADs was significantly (P < 0.01) correlated with HFA MD and
      CPSD. No other significant differences between OAG and controls were found.
      CONCLUSIONS: OAG patients show macular dysfunction detectable by the mfERG
      technique. Since the mfERG N1-P1 component is thought to be generated by
      preganglionic elements (photoreceptors and OFF bipolar cells), our data support
      the functional impairment of the neural generators of the macular region in
      patients with glaucoma.

PMID- 22969070
TI  - Effect of optical defocus on detection and recognition of vanishing optotype
      letters in the fovea and periphery.
AB  - PURPOSE: Vanishing optotypes (VOs) are pseudo high-pass letters whose mean
      luminance matches the background so that they "vanish" when the recognition
      acuity threshold is reached in the fovea. We determined the effect of increasing
      blur on acuity for these optotypes and conventional letters, in both foveal and
      extrafoveal viewing. METHODS: Detection and recognition thresholds were
      determined separately for each of the 26 letters of both a conventional and VO
      alphabet, both in the fovea and at 10 degrees  in the horizontal temporal retina,
      under varying degrees of positive dioptric blur. RESULTS: In the fovea, detection
      and recognition thresholds were similar for individual VOs, increased steadily
      with blur, and separated somewhat at higher levels of defocus (3 diopters [D]).
      While the recognition thresholds for VOs changed on average by 0.28 logarithm of
      the minimum angle of resolution (logMAR)/D, those for conventional letters
      changed more rapidly by 0.35 logMAR/D. In the periphery, recognition thresholds
      were significantly higher than detection thresholds for the VOs at 0 D blur; both
      thresholds increased steadily thereafter, converging as blur increased.
      Peripheral recognition acuity displayed a loss of only 0.09 logMAR/D. In both the
      fovea and periphery, the interletter variation in recognition acuity was much
      lower for VOs than conventional letters (0.04 vs. 0.09 logMAR). CONCLUSIONS:
      Outside the fovea, high-pass VOs display significant differences in their
      detection and resolution thresholds up to +7 D blur, with a logMAR/D loss of a
      quarter that of the fovea. The lower interletter legibility differences indicate
      that VO letters may be better stimuli from which to design clinical letter
      charts.

PMID- 22969071
TI  - Fluid circulation determined in the isolated bovine lens.
AB  - PURPOSE: In 1997, a theoretical model was developed that predicted the existence
      of an internal, Na(+)-driven fluid circulation from the poles to the equator of
      the lens. In the present work, we demonstrate with a novel system that fluid
      movement can be measured across the polar and equatorial surface areas of
      isolated cow lenses. We have also determined the effects of ouabain and reduced
      bath [Na(+)]. METHODS: Lenses were isolated in a chamber with three compartments
      separated by two thin O-rings. Each compartment, anterior (A), equatorial (E),
      and posterior (P), was connected to a vertical capillary graduated in 0.25 MUL.
      Capillary levels were read every 15 minutes. The protocols consisted of 2 hours
      in either open circuit or short circuit. The effects of ouabain and low-Na(+)
      solutions were determined under open circuit. RESULTS: In 21 experiments, the E
      capillary increased at a mean rate of 0.060 MUL/min while the A and P levels
      decreased at rates of 0.044 and 0.037 MUL/min, respectively, closely accounting
      for the increase in E. The first-hour flows under short circuit were
      approximately 40% larger than those in open-circuit conditions. The first-hour
      flows were always larger than those during the second hour. Preincubation of
      lenses with either ouabain or low-[Na(+)] solutions resulted in reduced rates of
      fluid transport. When KCl was used to replace NaCl, a transitory stimulation of
      fluid transport occurred. CONCLUSIONS: These experiments support that a fluid
      circulation consistent with the 1997 model is physiologically active.

PMID- 22969072
TI  - Visual functional and histopathological correlation in experimental autoimmune
      optic neuritis.
AB  - PURPOSE: To elucidate the correlation between visual threshold of optokinetic
      tracking (OKT), visual evoked potential (VEP), and histopathology at different
      time points after induction of experimental autoimmune optic neuritis (EAON).
      METHODS: EAON was induced in C57BL/6 mice by subcutaneous immunization with an
      emulsified mixture of myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide.
      OKT and VEP were measured on days 7, 14, 21, 28, and 42 postimmunization. After
      VEP measurements, the mice were killed and their eyes were enucleated for
      histopathological studies. Immunohistochemical staining was performed using cell
      specific markers for characterization of cells in the optic nerve: CD3 (T cells),
      Iba-1 (microglia), MBP (myelin basic protein), and neurofilament (axons).
      RESULTS: Functionally, OKT threshold decreased as early as day 7, and VEP latency
      was significantly prolonged on day 21. Axon degeneration was observed as early as
      day 14. Activated microglia infiltration was also observed on day 14, before T
      cell infiltration, which peaked on day 21. Demyelination, confirmed by MBP
      staining, was observed on day 21. CONCLUSIONS: Microglial infiltration in the
      optic nerve coincided with decline in OKT threshold and preceded VEP latency
      prolongation, while VEP latency prolongation coincided with T cell infiltration
      and demyelination of the optic nerve. These findings may contribute to
      understanding of the pathophysiology of optic neuritis and future development of
      more effective therapeutic strategy for refractory optic neuritis.

PMID- 22969073
TI  - NC1 long and NC3 short splice variants of type XII collagen are overexpressed
      during corneal scarring.
AB  - PURPOSE: To investigate type XII collagen expression in corneal scars in vivo.
      METHODS: Type XII collagen protein expression was evaluated by
      immunohistochemistry in human corneal scars and in a mouse model of corneal
      scarring at several time points (from day 7 to day 210) after full-thickness
      excision. Alternative splice variants of the NC3 and NC1 domains of type XII
      collagen were investigated in the mouse wound-healing model using RT-PCR.
      RESULTS: Type XII collagen was overexpressed in human corneal scars in areas that
      were also positive for alpha-smooth muscle actin staining. In a mouse model of
      corneal wound injury we found that at 14 and 21 days postexcision, type XII
      collagen was largely concentrated in the subepithelial region of the cornea,
      especially in and near the wound bed. By 28 days postexcision, expression of type
      XII collagen decreased but remained higher than that in controls. NC3 short form
      is the main form expressed in the cornea during the wound-healing process. After
      injury, the NC1 long splice variant mRNA was the most highly overexpressed
      variant in the cornea, especially in the epithelium (*2.7, 3.72, and 5.57 at days
      7, 14, and 21, respectively, P < 0.01 to 0.001 compared with uninjured samples).
      Corneal scars from a 7-month-old mouse revealed an overexpression of type XII
      collagen in the wound area similar to what we observed in human corneal scars.
      CONCLUSIONS: Type XII collagen is overexpressed in permanent human and mouse
      corneal scars and could represent a new target to treat corneal scarring.

PMID- 22969074
TI  - Involvement of RhoA/Rho-associated kinase signal transduction pathway in
      dexamethasone-induced alterations in aqueous outflow.
AB  - PURPOSE: We investigated the involvement of the RhoA/Rho kinase (ROCK) signal
      transduction pathway in dexamethasone (DEX)-induced changes in aqueous outflow.
      METHODS: Using trabecular meshwork (TM) and Schlemm's canal endothelial (SCE)
      cells, RhoA activation was evaluated with a pull-down assay and myosin light
      chain phosphorylation was evaluated by Western blot analysis. Outflow facility
      was measured in perfused porcine anterior segment organ cultures treated with DEX
      and/or Y-27632, a selective ROCK inhibitor. The barrier function of the cultured
      cells on a micropore filter was evaluated by measuring the transendothelial
      electrical resistance. Collagen, fibronectin, and integrin mRNA expression levels
      were evaluated by quantitative real-time RT-PCR. RESULTS: Relative RhoA
      activities increased following stimulation with 100 nM DEX in TM and SCE cells.
      Perfusion with DEX decreased outflow facility by 31.9 +/- 14.3% compared to
      controls at 24 hours, but not by 50 MUM Y-27632 in addition to DEX. The
      transendothelial electrical resistance of the SCE cell monolayer was increased by
      48.6 +/- 6.4% and 5.3 +/- 5.0% following DEX treatments without and with 10 MUM Y
      27632, respectively, compared to controls. In TM cells, the mRNA expressions of
      COL4A1 and fibronectin were increased significantly by DEX treatment, but
      combined treatment with Y-27632 and DEX significantly inhibited the increase in
      COL4A1 and fibronectin expression. CONCLUSIONS: Activation of the Rho/ROCK
      pathway in SCE cells contributes to the mechanism of DEX-induced changes in
      aqueous outflow.

PMID- 22969075
TI  - The retinal clock drives the expression of Kcnv2, a channel essential for visual
      function and cone survival.
AB  - PURPOSE: The gene Kcnv2 codes for the voltage-gated potassium channel subunit
      Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional
      voltage-gated potassium channels. Mutations in the Kcnv2 gene result in a retinal
      disorder designated "cone dystrophy with supernormal rod response (CDSRR),"
      revealing that Kcnv2 is essential for visual processing and cone survival. The
      aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under
      circadian regulation and may thus contribute to the clock-driven adjustment of
      photoreceptor function. METHODS: Expression of the genes was recorded in
      preparations of the whole retina and microdissected retinal neurons by using
      quantitative polymerase chain reaction and Western blot. RESULTS: The transcript
      levels of Kcnv2 and Kv2.1 in preparations of whole retina and photoreceptor cells
      were found to display daily rhythms, with elevated values during the night. For
      Kcnv2 this rhythm was shown to evoke a corresponding rhythm in Kv8.2, the protein
      product of this gene. The daily changes in retinal Kcnv2 and Kv2.1 mRNA levels
      persisted under constant darkness and are therefore driven by the endogenous
      retinal clock system, which itself is entrained by light. CONCLUSIONS: The
      present data provide evidence that the transcriptional regulation of Kcnv2 and
      Kv2.1 is a way through which the retinal clock system drives the functional
      adaptation of visual function to the marked daily changes in environmental
      lighting conditions.

PMID- 22969077
TI  - An anatomically customizable computational model relating the visual field to the
      optic nerve head in individual eyes.
AB  - PURPOSE: To present a computational model mapping visual field (VF) locations to
      optic nerve head (ONH) sectors accounting for individual ocular anatomy, and to
      describe the effects of anatomical variability on maps produced. METHODS: A
      previous model that related retinal locations to ONH sectors was adapted to model
      eyes with varying axial length, ONH position and ONH dimensions. Maps (n =
      11,550) relating VF locations (24-2 pattern, n = 52 non-blind-spot locations) to
      1 degrees  ONH sectors were generated for a range of clinically plausible
      anatomical parameters. Infrequently mapped ONH sectors (5%) were discarded for
      all locations. The influence of anatomical variables on the maps was explored by
      multiple linear regression. RESULTS: Across all anatomical variants, for
      individual VF locations (24-2), total number of mapped 1 degrees  ONH sectors
      ranged from 12 to 90. Forty-one locations varied more than 30 degrees . In five
      nasal-step locations, mapped ONH sectors were bimodally distributed, mapping to
      vertically opposite ONH sectors depending on vertical ONH position. Mapped ONH
      sectors were significantly influenced (P < 0.0002) by axial length, ONH position,
      and ONH dimensions for 39, 52, and 30 VF locations, respectively. On average
      across all VF locations, vertical ONH position explained the most variance in
      mapped ONH sector, followed by horizontal ONH position, axial length, and ONH
      dimensions. CONCLUSIONS: Relations between ONH sectors and many VF locations are
      strongly anatomy-dependent. Our model may be used to produce customized maps from
      VF locations to the ONH in individual eyes where some simple biometric parameters
      are known.

PMID- 22969078
TI  - Associations between metamorphopsia and foveal microstructure in patients with
      epiretinal membrane.
AB  - PURPOSE: To investigate the relationship between the severity of metamorphopsia
      and the foveal microstructure measured with spectral-domain optical coherence
      tomography (SD-OCT) in patients with epiretinal membrane (ERM). METHODS: This
      study included 48 eyes of 48 patients with idiopathic ERM and 18 age-matched
      normal controls. We examined the logarithm of the minimum angle of resolution
      best-corrected visual acuity (logMAR BCVA) and the severity of metamorphopsia
      using M-CHARTS. Central foveal thickness (CFT), central retinal thickness at the
      fovea (CRT-1mm) and parafovea (CRT-3mm), and macular volume (MV) were measured
      with SD-OCT software. Based on the obtained OCT image, we divided the 1.0 * 1.0
      mm area centered on the fovea into nine sections and quantified the following
      parameters using an image-processing program: mean thickness of the ganglion cell
      layer (GCL), inner nuclear layer (INL), and outer retinal layer (ONL+OPL: outer
      nuclear layer and outer plexiform layer), the degree of the photoreceptor inner
      and outer segment junction (IS/OS), and external limiting membrane (ELM)
      disruption. RESULTS: CFT, CRT-1mm, CRT-3mm, MV, mean GCL, INL, and ONL+OPL
      thickness were significantly larger in patients with ERM than in normal controls.
      Multiple regression analysis revealed that the severity of metamorphopsia was
      significantly related to the mean INL thickness (P < 0.0001). LogMAR BCVA had a
      significant correlation with the degree of IS/OS disruption (P < 0.05), whereas
      other parameters were not relevant. CONCLUSIONS: In patients with idiopathic ERM,
      the degree of metamorphopsia is associated with INL thickness, and IS/OS status
      influences visual acuity.

PMID- 22969076
TI  - Evaluation of ultrasound-assisted thrombolysis using custom liposomes in a model
      of retinal vein occlusion.
AB  - PURPOSE: To study the potential efficacy of ultrasound (US) assisted by custom
      liposome (CLP) destruction as an innovative thrombolytic tool for the treatment
      of retinal vein occlusion (RVO). METHODS: Experimental RVO was induced in the
      right eyes of 40 rabbits using laser photothrombosis; the US experiment took
      place 48 hours later. Rabbits were randomly divided into four equal groups:
      US+CLP group, US+saline group, CLP+sham US group, and no treatment group. The
      latter three groups acted as controls. Fundus fluorescein angiography and Doppler
      US were used to evaluate retinal blood flow. RESULTS: CLP-assisted US
      thrombolysis resulted in restoration of flow in seven rabbits (70%). None of the
      control groups showed significant restoration of retinal venous blood flow.
      CONCLUSIONS: US-assisted thrombolysis using liposomes resulted in a statistically
      significant reperfusion of retinal vessels in the rabbit experimental model of
      RVO. This approach might be promising in the treatment of RVO in humans. Further
      studies are needed to evaluate this approach in patients with RVO. Ultrasound
      assisted thrombolysis can be an innovative tool in management of retinal vein
      occlusion.

PMID- 22969079
TI  - Real-time PCR for detection of blaOXA-48 genes from stools.
AB  - OBJECTIVES: Outbreaks of OXA-48-like carbapenemase producers are increasingly
      reported in many European countries and are often the result of difficulties in
      detection, especially for isolates with MICs of carbapenems that remain in the
      susceptibility range. METHODS: An in-house real-time quantitative PCR (qPCR)
      assay using TaqMan chemistry to detect bla(OXA-48-like) genes was compared with
      bacterial culturing on ChromID ESBL and SUPERCARBA media of spiked stool samples
      with several species producing OXA-48 variants. RESULTS: qPCR amplification using
      plasmid DNA was linear over 10 log dilutions (r(2) = 0.998 and slope = -3.14),
      with an amplification efficiency of 1.10, and the detection limit of the assay
      was reproducibly estimated at 10 plasmid molecules/PCR. No cross-reaction was
      detected with DNA extracted from several multidrug-resistant bacteria harbouring
      other beta-lactam resistance genes. The bla(OXA-48) qPCR assay was capable of
      detecting 10-50 cfu of OXA-48 producers/100 mg of faeces. ChromID ESBL was
      capable of detecting OXA-48 producers (1 * 10(1) to 3 * 10(2) cfu/100 mg of
      faeces), as long as the isolates exhibited a high level of resistance to
      cephalosporins due to an associated extended-spectrum beta-lactamase. The
      SUPERCARBA screening medium was capable of detecting all the OXA-48-like
      producers (1-3 * 10(1) cfu/100 mg of faeces), except those producing OXA-163, a
      variant lacking carbapenem-hydrolysing activity. CONCLUSIONS: The qPCR is likely
      to shorten the time for bla(OXA-48) detection from 48 to 4 h and will be a
      valuable tool for outbreak follow-up in order to rapidly isolate colonized
      patients and assign them to cohorts.

PMID- 22969080
TI  - Complete sequencing of an IncHI1 plasmid encoding the carbapenemase NDM-1, the
      ArmA 16S RNA methylase and a resistance-nodulation-cell division/multidrug efflux
      pump.
AB  - OBJECTIVES: To characterize the pNDM-CIT plasmid identified in Citrobacter
      freundii carrying genes encoding the metallo-beta-lactamase NDM-1 and the 16S RNA
      methylase ArmA. METHODS: The complete DNA sequence of pNDM-CIT was obtained by
      using the 454-Genome Sequencer FLX procedure on a library obtained using plasmid
      DNA purified from the pNDM-CIT Escherichia coli J53 transconjugant. Contig
      assembly and predicted gaps were confirmed and filled by PCR-based gap closure.
      Comparative analysis with IncHI1 incompatibility group plasmids was performed
      using BLASTN and BLASTP algorithms. RESULTS: Plasmid pNDM-CIT was 288::920 bp and
      revealed an IncHI1 plasmid scaffold, showing novel resistance and potential
      virulence determinants. The bla(NDM-1) gene was identified within a novel genetic
      context, flanked by a duplication of the class 1 integron on both sides. The
      replicase gene repAciN, originating from Acinetobacter spp. plasmids, was
      identified in a close association with the Tn1548::armA transposon and the
      macrolide resistance mel-mph2 cluster. The same structure was identified in
      silico from a series of enterobacterial plasmids carrying the armA gene. The
      repAciN gene probably represents a remnant sign of the original occurrence of the
      armA gene in Acinetobacter plasmids. A CP4-like prophage sequence was identified
      in pNDM-CIT, containing a resistance-nodulation-cell division/multidrug
      resistance (RND/MDR) efflux pump cluster surrounded by two IS1-like elements.
      This resistance determinant, associated with such a prophage sequence, has never
      been reported on plasmids. CONCLUSIONS: Plasmid pNDM-CIT differed significantly
      from all known bla(NDM-1)-carrying plasmids identified in Enterobacteriaceae,
      since it combines the metallo-beta-lactamase NDM-1, the 16S RNA methylase ArmA
      and a cryptic prophage carrying the RND/MDR efflux pump.

PMID- 22969081
TI  - A model for calculating the within-subject biological variation and likelihood
      ratios for analytes with a time-dependent change in concentrations; exemplified
      with the use of D-dimer in suspected venous thromboembolism in healthy pregnant
      women.
AB  - BACKGROUND: Within-subject biological variation and reference change value (RCV)
      are difficult to calculate for an analyte with a changing concentration. The aim
      of this study was to develop a model to examine if it was possible to transform
      an analyte with a time-dependent change in concentration into a 'steady-state'
      situation by the use of 'multiples of the median' (MoM) and its natural logarithm
      (lnMoM). In addition, we wanted to extend the RCV concept, using likelihood and
      odds ratios, to calculate the post-test probabilities for disease. D-dimer in
      pregnancy is used as an example. METHODS: Blood samples from 18 healthy pregnant
      and 18 healthy non-pregnant women were collected every fourth week. MoM of the D
      dimer concentrations was calculated for each four-week interval to obtain a
      'steady-state' situation for the D-dimer concentrations. The 'normalized' values
      were then transformed to the lnMoM to obtain a Gaussian distribution, used for
      the estimation of biological variation. RESULTS: Median D-dimer concentrations
      increased six-fold during pregnancy. Within-subject variation (SD) of lnMoM D
      dimer was 0.27 during pregnancy and 0.23 in non-pregnant women, with RCVs of 0.72
      and 0.90, respectively. CONCLUSIONS: By using the lnMoM model, an increasing
      concentration of an analyte can be transformed to a steady-state situation and
      the within-subject biological variation and its derived parameters can be
      calculated.

PMID- 22969082
TI  - Lipid-dependent generation of dual topology for a membrane protein.
AB  - The mechanism by which membrane proteins exhibit structural and functional
      duality in the same membrane or different membranes is unknown. We posit that
      such duality is determined by both the protein sequence and the membrane lipid
      composition wherein a spatial or temporal change in the latter can result in a
      post-assembly change in protein structure and function. To investigate whether co
      existence of multiple topological conformers is dependent on the membrane lipid
      composition, we determined the topological organization of lactose permease in an
      Escherichia coli model cell system in which phosphatidylethanolamine membrane
      content can be systematically varied. At intermediate levels of
      phosphatidylethanolamine a mixture of native and topologically mis-oriented
      conformers co-existed. There was no threshold level of phosphatidylethanolamine
      determining a sharp transition from one conformer to the other. Co-existing
      conformers were not in rapid equilibrium at a static lipid composition indicating
      that duality of topology is established during an early folding step. Depletion
      of intermediate levels of phosphatidylethanolamine after final protein assembly
      resulted in complete mis-orientation of the native conformer. Combined with
      previous results, such topological dynamics are reversible in both directions. We
      propose a thermodynamically based model for how lipid-protein interactions can
      result in a mixed topological organization and how changes in lipid composition
      can result in changes in the ratio of topologically distinct conformers of
      proteins. These observations demonstrate a potential lipid-dependent biological
      switch for generating dynamic structural and functional heterogeneity for a
      protein within the same membrane or between different membranes in more complex
      eukaryotic cells.

PMID- 22969083
TI  - Structure and location of the regulatory beta subunits in the
      (alphabetagammadelta)4 phosphorylase kinase complex.
AB  - Phosphorylase kinase (PhK) is a hexadecameric (alphabetagammadelta)(4) complex
      that regulates glycogenolysis in skeletal muscle. Activity of the catalytic gamma
      subunit is regulated by allosteric activators targeting the regulatory alpha,
      beta, and delta subunits. Three-dimensional EM reconstructions of PhK show it to
      be two large (alphabetagammadelta)(2) lobes joined with D(2) symmetry through
      interconnecting bridges. The subunit composition of these bridges was unknown,
      although indirect evidence suggested the beta subunits may be involved in their
      formation. We have used biochemical, biophysical, and computational approaches to
      not only address the quaternary structure of the beta subunits within the PhK
      complex, i.e. whether they compose the bridges, but also their secondary and
      tertiary structures. The secondary structure of beta was determined to be
      predominantly helical by comparing the CD spectrum of an alphagammadelta
      subcomplex with that of the native (alphabetagammadelta)(4) complex. An atomic
      model displaying tertiary structure for the entire beta subunit was constructed
      using chemical cross-linking, MS, threading, and ab initio approaches. Nearly all
      this model is covered by two templates corresponding to glycosyl hydrolase 15
      family members and the A subunit of protein phosphatase 2A. Regarding the
      quaternary structure of the beta subunits, they were directly determined to
      compose the four interconnecting bridges in the (alphabetagammadelta)(4) kinase
      core, because a beta(4) subcomplex was observed through both chemical cross
      linking and top-down MS of PhK. The predicted model of the beta subunit was
      docked within the bridges of a cryoelectron microscopic density envelope of PhK
      utilizing known surface features of the subunit.

PMID- 22969084
TI  - Characterization of an actin-targeting ADP-ribosyltransferase from Aeromonas
      hydrophila.
AB  - The mono-ADP-ribosyltransferase (mART) toxins are contributing factors to a
      number of human diseases, including cholera, diphtheria, traveler's diarrhea, and
      whooping cough. VahC is a cytotoxic, actin-targeting mART from Aeromonas
      hydrophila PPD134/91. This bacterium is implicated primarily in diseases among
      freshwater fish species but also contributes to gastrointestinal and
      extraintestinal infections in humans. VahC was shown to ADP-ribosylate Arg-177 of
      actin, and the kinetic parameters were K(m)(NAD(+)) = 6 MUM, K(m)(actin) = 24
      MUM, and k(cat) = 22 s(-1). VahC activity caused depolymerization of actin
      filaments, which induced caspase-mediated apoptosis in HeLa Tet-Off cells.
      Alanine-scanning mutagenesis of predicted catalytic residues showed the predicted
      loss of in vitro mART activity and cytotoxicity. Bioinformatic and kinetic
      analysis also identified three residues in the active site loop that were
      critical for the catalytic mechanism. A 1.9 A crystal structure supported the
      proposed roles of these residues and their conserved nature among toxin
      homologues. Several small molecules were characterized as inhibitors of in vitro
      VahC mART activity and suramin was the best inhibitor (IC(50) = 20 MUM).
      Inhibitor activity was also characterized against two other actin-targeting mART
      toxins. Notably, these inhibitors represent the first report of broad spectrum
      inhibition of actin-targeting mART toxins.

PMID- 22969085
TI  - Structural and functional characterization of VanG D-Ala:D-Ser ligase associated
      with vancomycin resistance in Enterococcus faecalis.
AB  - d-Alanyl:d-lactate (d-Ala:d-Lac) and d-alanyl:d-serine ligases are key enzymes in
      vancomycin resistance of Gram-positive cocci. They catalyze a critical step in
      the synthesis of modified peptidoglycan precursors that are low binding affinity
      targets for vancomycin. The structure of the d-Ala:d-Lac ligase VanA led to the
      understanding of the molecular basis for its specificity, but that of d-Ala:d-Ser
      ligases had not been determined. We have investigated the enzymatic kinetics of
      the d-Ala:d-Ser ligase VanG from Enterococcus faecalis and solved its crystal
      structure in complex with ADP. The overall structure of VanG is similar to that
      of VanA but has significant differences mainly in the N-terminal and central
      domains. Based on reported mutagenesis data and comparison of the VanG and VanA
      structures, we show that residues Asp-243, Phe-252, and Arg-324 are molecular
      determinants for d-Ser selectivity. These residues are conserved in both enzymes
      and explain why VanA also displays d-Ala:d-Ser ligase activity, albeit with low
      catalytic efficiency in comparison with VanG. These observations suggest that d
      Ala:d-Lac and d-Ala:d-Ser enzymes have evolved from a common ancestral d-Ala:d-X
      ligase. The crystal structure of VanG showed an unusual interaction between two
      dimers involving residues of the omega loop that are deeply anchored in the
      active site. We constructed an octapeptide mimicking the omega loop and found
      that it selectively inhibits VanG and VanA but not Staphylococcus aureus d-Ala:d
      Ala ligase. This study provides additional insight into the molecular evolution
      of d-Ala:d-X ligases and could contribute to the development of new structure
      based inhibitors of vancomycin resistance enzymes.

PMID- 22969086
TI  - A role for protein inhibitor of activated STAT1 (PIAS1) in lipogenic regulation
      through SUMOylation-independent suppression of liver X receptors.
AB  - Liver X receptors (LXRs) are nuclear receptors that function to modulate lipid
      metabolism as well as immune and inflammatory responses. Upon activation by their
      ligands, LXRs up-regulate a spectrum of gene transcription programs involved in
      cholesterol and fatty acid homeostasis. However, the mechanisms by which LXR
      mediated transcriptional activation is regulated remain incompletely understood.
      Here, we show that PIAS1, a member of the protein inhibitor of the activated STAT
      family of proteins with small ubiquitin-like modifier (SUMO) E3 ligase activity,
      acts to suppress LXR ligand-dependent transcriptional activation of the lipogenic
      program in hepatocytes. We found that liver mRNA expression levels of Pias1 and
      Pias3 were inversely associated with those of genes involved in lipogenesis in
      mouse models with diet-induced or genetic obesity. Overexpression of PIAS1 in
      primary hepatocytes resulted in a reduction of LXR ligand-induced fatty acid
      synthesis and suppression of the expression of lipogenic genes, including Srebp1c
      and Fas. Moreover, PIAS1 was able to interact with LXRbeta and repress its
      transcriptional activity upon ligand stimulation, which did not require PIAS1
      promoted SUMO modification of LXRbeta. In addition, PIAS1 could also interact
      with PGC-1beta and attenuate its association with LXRbeta, blunting the ability
      of PGC-1beta to co-activate LXRbeta. Importantly, PIAS1 impaired LXRbeta binding
      to its target DNA sequence. Taken together, our results suggest that PIAS1 may
      serve as a lipogenic regulator by negatively modulating LXRs in a SUMOylation
      independent manner.

PMID- 22969087
TI  - Substrate-bound crystal structures reveal features unique to Mycobacterium
      tuberculosis N-acetyl-glucosamine 1-phosphate uridyltransferase and a catalytic
      mechanism for acetyl transfer.
AB  - N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme
      involved in bacterial cell wall synthesis is exclusive to prokaryotes. GlmU, now
      recognized as a promising target to develop new antibacterial drugs, catalyzes
      two key reactions: acetyl transfer and uridyl transfer at two independent
      domains. Hitherto, we identified GlmU from Mycobacterium tuberculosis (GlmU(Mtb))
      to be unique in possessing a 30-residue extension at the C terminus. Here, we
      present the crystal structures of GlmU(Mtb) in complex with substrates/products
      bound at the acetyltransferase active site. Analysis of these and mutational
      data, allow us to infer a catalytic mechanism operative in GlmU(Mtb). In this
      S(N)2 reaction, His-374 and Asn-397 act as catalytic residues by enhancing the
      nucleophilicity of the attacking amino group of glucosamine 1-phosphate. Ser-416
      and Trp-460 provide important interactions for substrate binding. A short helix
      at the C-terminal extension uniquely found in mycobacterial GlmU provides the
      highly conserved Trp-460 for substrate binding. Importantly, the structures
      reveal an uncommon mode of acetyl-CoA binding in GlmU(Mtb); we term this the U
      conformation, which is distinct from the L conformation seen in the available non
      mycobacterial GlmU structures. Residues, likely determining U/L conformation,
      were identified, and their importance was evaluated. In addition, we identified
      that the primary site for PknB-mediated phosphorylation is Thr-418, near the
      acetyltransferase active site. Down-regulation of acetyltransferase activity upon
      Thr-418 phosphorylation is rationalized by the structures presented here.
      Overall, this work provides an insight into substrate recognition, catalytic
      mechanism for acetyl transfer, and features unique to GlmU(Mtb), which may be
      exploited for the development of inhibitors specific to GlmU.

PMID- 22969089
TI  - Perfusion curve f (t) analysis of breast cancer by contrast-enhanced
      ultrasonography.
AB  - BACKGROUND: Imaging the perfusion of contrast media in breast tumors may allow
      improved diagnosing and treating breast cancer. PURPOSE: To compare the perfusion
      curve f (t) characteristics of contrast-enhanced ultrasonography in benign and
      malignant breast tumors. MATERIAL AND METHODS: Patients with breast tumors (n =
      87) were evaluated with contrast-enhanced ultrasonography and the perfusion curve
      f (t) parameters were calculated using Sonoliver((r)) software to compare
      analysis (tumor) and reference (normal) tissue areas. Differences between breast
      and breast tumors were assessed. RESULTS: Compared to benign tumors, malignant
      tumors had faster enhancement time and a shorter mean transit time (all P values
      < 0.05). The intensity of the signal was also greater for malignant compared with
      benign tumors. CONCLUSION: Perfusion curve f (t) parameter measurements can
      distinguish differences in vascular flow between malignant and benign breast
      tumors and may provide a new quantitative indicator of breast tumor.

PMID- 22969088
TI  - Modeling, substrate docking, and mutational analysis identify residues essential
      for the function and specificity of a eukaryotic purine-cytosine NCS1
      transporter.
AB  - The recent elucidation of crystal structures of a bacterial member of the NCS1
      family, the Mhp1 benzyl-hydantoin permease from Microbacterium liquefaciens,
      allowed us to construct and validate a three-dimensional model of the Aspergillus
      nidulans purine-cytosine/H(+) FcyB symporter. The model consists of 12
      transmembrane alpha-helical, segments (TMSs) and cytoplasmic N- and C-tails. A
      distinct core of 10 TMSs is made of two intertwined inverted repeats (TMS1-5 and
      TMS6-10) that are followed by two additional TMSs. TMS1, TMS3, TMS6, and TMS8
      form an open cavity that is predicted to host the substrate binding site. Based
      on primary sequence alignment, three-dimensional topology, and substrate docking,
      we identified five residues as potentially essential for substrate binding in
      FcyB; Ser-85 (TMS1), Trp-159, Asn-163 (TMS3), Trp-259 (TMS6), and Asn-354 (TMS8).
      To validate the role of these and other putatively critical residues, we
      performed a systematic functional analysis of relevant mutants. We show that the
      proposed substrate binding residues, plus Asn-350, Asn-351, and Pro-353 are
      irreplaceable for FcyB function. Among these residues, Ser-85, Asn-163, Asn-350,
      Asn-351, and Asn-354 are critical for determining the substrate binding affinity
      and/or the specificity of FcyB. Our results suggest that Ser-85, Asn-163, and Asn
      354 directly interact with substrates, Trp-159 and Trp-259 stabilize binding
      through pi-pi stacking interactions, and Pro-353 affects the local architecture
      of substrate binding site, whereas Asn-350 and Asn-351 probably affect substrate
      binding indirectly. Our work is the first systematic approach to address
      structure-function-specificity relationships in a eukaryotic member of NCS1
      family by combining genetic and computational approaches.

PMID- 22969090
TI  - Comparison of visibility for four self-expanding nitinol bare stents in vitro.
AB  - BACKGROUND: Sufficient radiopacity of stents is a prerequisite for safe
      interventions and minimization of the radiation dose for the patient and the
      interventionist. Modern nitinol stents are considered less radiopaque compared to
      formerly used stents. PURPOSE: To evaluate the objective detection rate (ODR) and
      the subjective radiopacity score (SRS) of four self-expanding nitinol stents with
      their markers on a phantom human pelvis. MATERIAL AND METHODS: We evaluated the
      ODR (as a percentage of correctly identified stents) and the SRS (on a scale from
      0 = not visible to 4 = excellent visibility) for four self-expanding nitinol
      stents (SinusSuperflex, SMART, Luminexx, Zilver) with 8 mm diameter and 40 mm
      length. Stents were placed on a phantom human pelvis and images of the stents
      were taken in four different positions (right and left lumbosacral joint and near
      the right and left limbus acetabuli) using the following modes: spotfilm, pulsed
      fluoroscopy (4, 7.5, 15, and 30 pulses/min) and at three different digital
      magnification modes. Dose area products (DAPs) were assessed. RESULTS: ODR and
      SRS, respectively, were significantly increased for the SMART stent compared to
      all other tested stents (P < 0.05): SMART 93.53% and 2.43, SinusSuperflex 90.81%
      and 2.21, Luminexx 90.39% and 2.20, and Zilver 89.28% and 2.21. ODR was
      significantly reduced in position 3 where the bone overlap was more pronounced
      for all stents (detection rates 77.14-79.56%). An increase in magnification
      significantly improved the ODR and SRS for all stents (70.33-99.25% and 1.07
      3.28, respectively, P < 0.05). Increased pulsing frequency did not improve the
      ODR of the various stents but did increase the DAP. CONCLUSION: The SMART stent
      had the best overall performance. In the presence of bone overlap, all self
      expanding nitinol stents had poor results. Increased pulsing frequency did not
      improve ODR or SRS but did increase the DAP. Use of digital magnification modes
      had no effect on DAP increasing ODR and SRS.

PMID- 22969091
TI  - Critical role of farnesoid X receptor for hepatocellular carcinoma cell
      proliferation.
AB  - Farnesoid X receptor (FXR), a pivotal factor maintaining bile acid homeostasis,
      has been recently shown to be a critical factor required for liver regeneration.
      The elucidation of the mechanism how FXR controls the proliferation of
      hepatocellular carcinoma cells is useful to establish the therapy for liver
      cancer. Here, we show that FXR plays a crucial role in the proliferation of human
      hepatocellular carcinoma cell line, HepG2, Huh7 and HLE. The treatment of HepG2
      with FXR siRNA elevates the level of p16/INK4a expression resulting in the
      inhibition of cell proliferation. By contrast, FXR activation reduces p16/INK4a
      expression and stimulates the cell proliferation. The ectopic expression of the
      active form of Ras that causes strong activation of extracellular signal
      regulated kinase (ERK) leads to the decrease in FXR expression, suggesting that
      FXR expression is negatively regulated via Ras/ERK pathway. The elevation of
      p16/INK4a expression and the inhibition of cell proliferation by FXR knockdown
      are also observed in Huh7 and HLE. In this study, we have suggested a novel
      mechanism by which hepatocellular carcinoma cell proliferation is regulated: FXR
      stimulates cell proliferation by suppressing the p16/INK4a expression, whereas
      Ras/ERK pathway down-regulates the FXR expression, leading to the suppressed cell
      proliferation in hepatocellular carcinoma cell lines.

PMID- 22969092
TI  - Evaluation of clinical threshold policies for cataract surgery among English
      commissioners.
AB  - OBJECTIVES: To ascertain if access to cataract surgery is being restricted in
      England and to describe any explicit threshold criteria. METHODS: A survey of 151
      local commissioners to explore their cataract surgery policy. A literature review
      identified research evidence about thresholds for cataract surgery. A checklist
      was devised and applied to the policies supplied by commissioners. RESULTS:
      Almost half (71/151) of commissioners were restricting access to surgery and this
      included patients with some capacity to benefit. There was wide variation in the
      scope and content of the 67 policies which were available for review. Almost all
      (92%) commissioners use criteria that do not reflect guidance or research
      evidence. CONCLUSIONS: Patients who could benefit from cataract surgery are being
      excluded by some commissioners. Variations in policy between commissioners
      results in inequalities in access.

PMID- 22969102
TI  - Q&A: Robert Comis and Mitchell Schnall on trials. Interview by Eric Bender.
AB  - The co-chairs of ECOG-ACRIN talk about combining forces to advance clinical
      studies.

PMID- 22969103
TI  - Immunotherapy network launches first trial.

PMID- 22969114
TI  - Whole-genome sequencing and cancer therapy: is too much ever enough?
AB  - This issue of Cancer Discovery features an article that describes the use of
      whole-genome sequencing to discover an actionable genetic alteration that was not
      detected using a lower resolution diagnostic approach. This finding highlights
      the growing debate surrounding the optimal deployment of powerful new genomics
      technologies in the clinical oncology arena.

PMID- 22969115
TI  - A genetic snapshot of small cell lung cancer.
AB  - Overexpression of PARP1 and enhancer of zeste homolog 2 (EZH2) has been
      identified in an integrated analysis of multiple proteins involved in
      intracellular signaling pathways in small cell lung cancer (SCLC) cell lines. The
      knockdown of PARP1 and EZH2 abrogated SCLC growth. These findings provide the
      basis for novel predictive markers and new treatment strategies in SCLC, for
      which there is now a paucity of available therapies.

PMID- 22969116
TI  - Desmoplasia: a response or a niche?
AB  - Desmoplasia--the presence of a rich stroma around a tumor--has long been
      associated with a poor clinical outcome in patients with cancer. It is considered
      to be a response to the presence of invasive tumor cells. There is now evidence
      that desmoplasia is the result of coordinated changes in several stromal cells
      under the control of a single gene product, CD36, whose repression leads to a
      decrease in fat accumulation and an increase in matrix deposition. The presence
      of these changes in tumor-free human breast tissue strongly suggests that
      desmoplasia may precede and not always follow the presence of malignant cells.
      This concept has an important clinical implication for women at high risk of
      developing breast carcinoma, considering that the presence of desmoplasia in
      normal breast tissue detected in the form of mammographic density is one of the
      strongest risk factors.

PMID- 22969117
TI  - Paracrine signaling between carcinoma cells and mesenchymal stem cells generates
      cancer stem cell niche via epithelial-mesenchymal transition.
AB  - Li and colleagues present data that cancer cell-derived interleukin-1 induces
      prostaglandin E(2) and cytokine secretion in mesenchymal stem cells (MSC) to
      activate beta-catenin signaling in the cancer cell. This paracrine signaling
      between carcinoma cells and MSC leads to the creation of a cancer stem cell niche
      via epithelial-mesenchymal transition.

PMID- 22969138
TI  - Endometrial and endometriotic concentrations of estrone and estradiol are
      determined by local metabolism rather than circulating levels.
AB  - CONTEXT: Aberrant estrogen synthesis and metabolism have been suggested to
      increase local estradiol (E2) concentration in endometriosis and thus to promote
      the growth of the lesions. However, tissue estrogen concentrations within the
      endometrium and different types of endometriosis lesions have not been described.
      OBJECTIVE: The aim of the study was to evaluate local E2 and estrone (E1)
      concentrations in the endometrium and different types of endometriosis lesions,
      and to correlate them with the expression of estrogen-metabolizing enzymes.
      PATIENTS: Patients with endometriosis (n = 60) and healthy controls (n = 16)
      participated in the study. MAIN OUTCOME MEASURES: We measured serum and tissue
      concentrations of E2 and E1 as well as mRNA expression of the estrogen
      metabolizing enzymes. RESULTS: Endometrial or endometriotic intratissue E2
      concentrations did not reflect the corresponding serum levels. In the
      proliferative phase, endometrial E2 concentration was five to eight times higher
      than in the serum, whereas in the secretory phase the E2 concentration was about
      half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was
      observed in the endometrium at the proliferative phase compared with the
      secretory phase. In the endometriosis lesions, E2 levels were predominating over
      those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17beta)
      dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the
      E2 concentration in the endometrium, and HSD17B6 was strongly expressed,
      especially in the deep lesions. CONCLUSIONS: Endometrial or endometriotic tissue
      E2 concentrations are actively regulated by local estrogen metabolism in the
      tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to
      reduce local E2-dependent growth of endometriotic tissue.

PMID- 22969139
TI  - Metaphyseal bone collapse mimicking slipped capital femoral epiphysis in severe
      renal osteodystrophy.
AB  - CONTEXT: Slipped capital femoral epiphysis is a well-recognized skeletal
      complication of renal osteodystrophy in adolescence, which is distinct from
      idiopathic slipped capital femoral epiphysis in its etiology. OBJECTIVE: We
      report a case of severe mixed-type renal osteodystrophy with metaphyseal bone
      collapse that mimicked slipped capital femoral epiphyses. METHODS: Case history,
      laboratory and radiological evaluation, and bone biopsies are discussed. RESULTS:
      A 14-yr-old girl presented with left hip pain showing bilateral metaphyseal bone
      collapse accompanied with posterior-inferior displacement of capital femoral
      epiphyses after 2.5 yr of GH treatment. Blood chemistry, showing high levels of
      alkaline phosphatase and PTH, and a transiliac bone biopsy, indicating severe
      osteomalacia with osteitis fibrosa, along with serial computed tomography images
      of the hips from the presymptomatic stage, led to accurate diagnosis and
      successful treatment by administration of high-dose vitamin D. CONCLUSION: This
      case emphasizes the importance of controlling hyperparathyroidism well in
      children with chronic renal insufficiency, particularly at adolescence before
      initiating GH treatment. When children with renal insufficiency present with
      displacement of capital femoral epiphysis, it is necessary to evaluate the serum
      levels of alkaline phosphatase and PTH and metaphyseal bone quality below the
      physis.

PMID- 22969140
TI  - Endothelial function is impaired across the stages of the menopause transition in
      healthy women.
AB  - CONTEXT: The stages of the menopause transition are characterized by changes in
      ovarian hormones and increased cardiovascular disease (CVD) risk factors and
      vasomotor symptoms that may adversely affect vascular health. OBJECTIVE: We
      tested the hypothesis that endothelial function, a predictor of CVD, would be
      reduced across the stages of the menopause transition, independent of CVD risk
      factors and vasomotor symptoms. DESIGN, SETTING, AND PARTICIPANTS: This was a
      cross-sectional study of 132 healthy women from the general community aged 22-70
      yr, categorized as premenopausal (n = 33, 32 +/- 6 yr; mean +/- SD), early
      perimenopausal (n = 20, 49 +/- 3 yr) or late perimenopausal (n = 22, 50 +/- 4
      yr), or early (n = 30, 55 +/- 3 yr) or late postmenopausal (n = 27, 61 +/- 4 yr).
      MAIN OUTCOME: Endothelial-dependent vasodilation was measured by brachial artery
      flow-mediated dilation (FMD) using ultrasound. RESULTS: Brachial artery FMD was
      significantly different among the groups (P < 0.001). It was highest in
      premenopausal women (9.9 +/- 2.1%) with progressive decrements in perimenopausal
      (early: 8.2 +/- 2.5%; late: 6.5 +/- 1.9%) and postmenopausal women (early: 5.5 +/
      1.9%; late: 4.7 +/- 1.7%). Adjustment for risk factors, vasomotor symptoms, and
      sex hormones did not alter the association (P < 0.001). In subgroup analyses of
      women aged 50-59 yr, brachial artery FMD was lower in late peri- and early and
      late postmenopausal compared with early perimenopausal women (P < 0.001) but was
      not different between late perimenopausal and either early or late postmenopausal
      women. CONCLUSIONS: Our findings suggest that a decline in endothelial function
      begins during the early stages of menopause (perimenopause) and worsens with the
      loss of ovarian function and prolonged estrogen deficiency. These data add to the
      accumulating evidence that the perimenopausal window is a critical time period
      for adverse changes in CVD risk.

PMID- 22969141
TI  - Xanthogranuloma, Rathke's cyst, and childhood craniopharyngioma: results of
      prospective multinational studies of children and adolescents with rare sellar
      malformations.
AB  - CONTEXT: Craniopharyngioma (CP), Rathke's cyst (RC), and xanthogranuloma (XG) are
      closely related rare sellar masses. Treatment strategies in children lack
      consensus. OBJECTIVE: Our objective was to study clinical manifestations and
      treatment-related outcome in RC, XG, and CP patients. DESIGN: We conducted a
      multicenter surveillance trial. PATIENTS: Inclusion criteria were 1) histological
      diagnosis of CP, XG, or RC and 2) diagnosis at age of 18 yr or less. A total of
      117 CP, 14 XG (2001-2006), and 14 RC (1996-2006) were recruited. MAIN OUTCOME:
      Overall survival (OS), event-free survival (EFS), and quality of life (QoL) were
      evaluated. RESULTS: The 5-yr OS rates were 1.00 +/- 0.00 in RC and XG and 0.97 +/
      0.02 in CP. The 5-yr EFS rates were 0.85 +/- 0.10 in RC, 1.00 +/- 0.00 in XG,
      and 0.50 +/- 0.05 in CP. Surgical resection of XG results in complete remission
      without recurrence. Recurrences occur in RC (14%) and CR (59%) but can be
      efficiently treated by irradiation, reoperation, and/or intracystic treatment.
      Severe hypothalamic sequelae such as obesity and others affecting QoL are
      predominant in CP due to presurgical involvement (59%) and postsurgical lesions
      (44%) of posterior hypothalamic structures. Centers with lower neurosurgery
      patient load use more radical surgical approaches to treat CP, resulting in
      higher rates of obesity and reduced QoL. Despite 46% anterior hypothalamic
      involvement, severe obesity is not encountered in XG. CONCLUSIONS: Treatment of
      choice in XG and RC is radical surgery. In CP involving hypothalamic structures,
      less radical surgical approaches preserving hypothalamic integrity are
      recommended. Due to frequent relapses, regular imaging during follow-up is
      recommended for CP and RC. Treatment of patients with sellar masses should be
      confined to experienced multidisciplinary teams.

PMID- 22969142
TI  - Insights into mentorship for endocrinologists.
AB  - CONTEXT: Effective mentorship is considered a prerequisite for success during
      medical training and an ensuing professional career in academic medicine. The
      Endocrine Society established sessions on mentorship at the Trainee Day during
      several annual meetings. These requests motivated a group of endocrinologists at
      the University of Virginia to assess prior literature on mentorship and collect
      opinions on the importance of the various characteristics of mentorship from
      endocrinologists, general faculty, and trainees. This information served as the
      basis for in-depth reflection and discussions on mentorship. OBJECTIVE: The goal
      was to identify and prioritize the quintessential elements involved in mentorship
      and to reach practical conclusions that would be beneficial to academic
      endocrinologists. COMMENTARY: A multigenerational mentorship tree emphasizes that
      successful mentors can influence generations of mentees and that this represents
      a multiplier effect. The authors propose that trainees who are informed about the
      most important characteristics of an effective mentor can make better choices of
      a mentor. On the other hand, mentors can best define expectations when mentees
      know what to expect from a mentor, based on key characteristics. CONCLUSIONS:
      Similarities and differences in expectation about mentorship can be leveraged for
      better communication between mentor and mentee and for the development of stage
      appropriate educational curricula on academic mentorship.

PMID- 22969143
TI  - An initiative to facilitate well-informed decision-making in laboratory animal
      research: report of the First International Symposium on Systematic Reviews in
      Laboratory Animal Science.

PMID- 22969144
TI  - The pig as an experimental model for clinical craniofacial research.
AB  - The pig represents a useful, large experimental model for biomedical research.
      Recently, it has been used in different areas of biomedical research. The aim of
      this study was to review the basic anatomical structures of the head region in
      the pig in relation to their use in current research. Attention was focused on
      the areas that are frequently affected by pathological processes in humans: the
      oral cavity with teeth, salivary gland, orbit, nasal cavity and paranasal
      sinuses, maxilla, mandible and temporomandibular joint. Not all of the structures
      have an equal morphology in the pig and human, and these morphological
      dissimilarities must be taken into account before choosing the pig as an
      experimental model for regenerative medicine.

PMID- 22969145
TI  - Voluntary ingestion of nut paste for administration of buprenorphine in rats and
      mice.
AB  - An adequate analgesic strategy is important to improve the postoperative recovery
      and welfare of laboratory rats and mice. It is desirable that the method for
      administering the drug is non-invasive and stress-free. We have previously
      validated a method for administering buprenorphine in a nut paste for voluntary
      ingestion. This method has many advantages over parenteral administration. To use
      the method in a successful way, however, it is important to prepare and
      administer the mix correctly. The present paper describes in detail how to
      implement the method, by means of habituation, presentation, adequate
      concentrations and amounts of buprenorphine/nut paste, and dosage of
      buprenorphine to rats and mice.

PMID- 22969146
TI  - A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of
      chronic daily medication to rats.
AB  - Stress can influence a number of physiological processes including adult
      neurogenesis, metabolism, cardiovascular function, immune function,
      neurophysiological function, endocrine function and inflammatory processes
      following injury. In testing drugs which may be used to treat various diseases or
      injuries, reducing stress associated with chronic drug delivery to animal models
      should then be an imperative, which led us to design a reliable voluntary oral
      drug delivery method. Various drug combinations were tested versus vehicle
      controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and
      Sprague Dawley) with our voluntary oral delivery system. Oral medications were
      placed into a store-bought sugar cookie dough ball (~4 g), thoroughly integrating
      the dry drugs with the dough. This method has worked consistently to deliver the
      medication (complete ingestion) in four different stocks or strains of rats, with
      reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or
      strain that have at any time during the study had incomplete ingestion of the
      drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to
      approximately 16% in Long Evans. Both serum and brain samples were analysed for
      high-performance liquid chromatography (HPLC) detection of one of our
      administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are
      detectable 2-4 h after ingestion, but not 24 h after ingestion. Brain samples
      however, showed detectable levels of both fluoxetine and norfluoxetine more than
      a week following ingestion of a single dose, with higher norfluoxetine levels
      seen following a month of daily administered drugs.

PMID- 22969147
TI  - Temporal molecular and biological assessment of an erlotinib-resistant lung
      adenocarcinoma model reveals markers of tumor progression and treatment response.
AB  - Patients with lung cancer with activating mutations in the EGF receptor (EGFR)
      kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often
      develop secondary mutations in EGFR associated with resistance. Mice engineered
      to develop lung adenocarcinomas driven by the human EGFR T790M resistance
      mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume
      endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible
      EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven
      changes in the lung with response to drug treatment, we conducted an integrative
      analysis of global transcriptome and metabolite profiling compared with
      quantitative imaging and histopathology at several time points during tumor
      progression and treatment. Responses to single-drug treatments were temporary,
      whereas combination therapy elicited a sustained response. During tumor
      development, metabolomic signatures indicated a shift to high anabolic activity
      and suppression of antitumor programs with 11 metabolites consistently present in
      both lung tissue and blood. Combination drug treatment reversed many of the
      molecular changes found in tumored lung. Data integration linking cancer
      signaling networks with metabolic activity identified key pathways such as
      glutamine and glutathione metabolism that signified response to single or dual
      treatments. Results from combination drug treatment suggest that metabolic
      transcriptional control through C-MYC and SREBP, as well as ELK1, NRF1, and NRF2,
      depends on both EGFR and mTORC1 signaling. Our findings establish the importance
      of kinetic therapeutic studies in preclinical assessment and provide in vivo
      evidence that TKI-mediated antiproliferative effects also manifest in specific
      metabolic regulation.

PMID- 22969148
TI  - The physiological impact of upper limb position in prone restraint.
AB  - Deaths occurring during and/or in close proximity to physical restraint have been
      attributed to positional asphyxia. This study investigated the physiological
      impact of three recognized prone-restraint positions with participants remaining
      passive. Position 3 (P3) the supported prone position (SPP) was designed to
      reduce the extent of pressure on the anterior chest wall (PAC) by bringing the
      upper limbs underneath the shoulder joint whereas for the other two positions (P1
      and P2) the arms were abducted from the torso. Twenty-five adults participated.
      Forced vital capacity (FVC), expiratory volume in one second (FEV1), heart rate
      (HR) and oxygen saturations (SpO2) were taken three times in an upright seated
      position (baseline) and in each prone position. Mean PAC was measured at 102.6
      (+/-24.3) and 101.4 (+/-24.4) mmHg for P1 and P2, respectively; however, in the
      SPP (P3) the mean PAC pressure reduced to 72.7 (+/-16.9) mmHg. All three prone
      restraint positions reduced FVC and FEV1 compared with baseline (P < 0.001). P1
      and P2 where the arms were abducted reduced respiratory measures equally but
      differed from the SPP position (P < 0.001) where PAC was significantly lower.
      Reductions in FVC from baseline were 16% for P1 and P2, and 11% for the SPP (P3)
      where PAC was ~28% lower than in P1 and P2. Reductions in FEV1 were similar in
      all three prone-restraint positions and HR and SpO2 were unaffected. In summary,
      all prone-restraint positions restrict respiratory function but the risk
      associated with the position reduces as the PAC reduces. 

PMID- 22969149
TI  - A(H1N1)pdm09 vaccination of health care workers: improved immune responses in low
      responders following revaccination.
AB  - BACKGROUND: We conducted a clinical trial in October 2009 to evaluate the
      immunogenicity of the AS03-adjuvanted influenza vaccine (pH1N1 vaccine) in health
      care workers (HCWs). By 2 weeks after vaccination, 97% had protective
      hemagglutinin inhibition (HI) titers (>= 40) however, 16% were low responders
      (LR) and failed to maintain a protective response 90 days after vaccination.
      METHODS: We analyzed the humoral responses (HI, antibody-secreting cell [ASC],
      and serum immunoglobulin G [IgG]) in 15 LRs and 25 control HCWs. Twelve LRs were
      revaccinated with the pH1N1 vaccine, and 7 were subsequently vaccinated with the
      2010 seasonal trivalent influenza vaccine. We conducted a long-term analysis of
      the humoral and CD4(+) T-helper (Th) 1 responses. RESULTS: The LRs had a slower
      HI antibody response than the control HCWs, with protective antibody titers not
      reached until 2 weeks after vaccination in the majority of the participants. The
      LRs also had significantly lower IgG ASCs at day 7 and HA1-specific serum IgG
      responses at day 21, compared with the control HCWs. Revaccination with the pH1N1
      vaccine elicited rapid HI antibody, ASC, memory B cell, and multifunctional
      CD4(+) Th1 cell responses. CONCLUSION: This study shows that revaccination of low
      responding HCWs with the pH1N1 vaccine is required for maintaining long-term
      protection. CLINICAL TRIALS REGISTRATION: NCT01003288.

PMID- 22969150
TI  - Distinguishing prodromal from first-episode psychosis using neuroanatomical
      single-subject pattern recognition.
AB  - BACKGROUND: The at-risk mental state for psychosis (ARMS) and the first episode
      of psychosis have been associated with structural brain abnormalities that could
      aid in the individualized early recognition of psychosis. However, it is unknown
      whether the development of these brain alterations predates the clinical
      deterioration of at-risk individuals, or alternatively, whether it parallels the
      transition to psychosis at the single-subject level. METHODS: We evaluated the
      performance of an magnetic resonance imaging (MRI)-based classification system in
      classifying disease stages from at-risk individuals with subsequent transition to
      psychosis (ARMS-T) and patients with first-episode psychosis (FE). Pairwise and
      multigroup biomarkers were constructed using the structural MRI data of 22
      healthy controls (HC), 16 ARMS-T and 23 FE subjects. The performance of these
      biomarkers was measured in unseen test cases using repeated nested cross
      validation. RESULTS: The classification accuracies in the HC vs FE, HC vs ARMS-T,
      and ARMS-T vs FE analyses were 86.7%, 80.7%, and 80.0%, respectively. The
      neuroanatomical decision functions underlying these discriminative results
      particularly involved the frontotemporal, cingulate, cerebellar, and subcortical
      brain structures. CONCLUSIONS: Our findings suggest that structural brain
      alterations accumulate at the onset of psychosis and occur even before transition
      to psychosis allowing for the single-subject differentiation of the prodromal and
      first-episode stages of the disease. Pattern regression techniques facilitate an
      accurate prediction of these structural brain dynamics at the early stage of
      psychosis, potentially allowing for the early recognition of individuals at risk
      of developing psychosis.

PMID- 22969151
TI  - Biochemical and pharmacological characterization of human alpha/beta-hydrolase
      domain containing 6 (ABHD6) and 12 (ABHD12).
AB  - In the central nervous system, three enzymes belonging to the serine hydrolase
      family are thought to regulate the life time of the endocannabinoid 2
      arachidonoylglycerol (C20:4) (2-AG). From these, monoacylglycerol lipase (MAGL)
      is well characterized and, on a quantitative basis, is the main 2-AG hydrolase.
      The postgenomic proteins alpha/beta-hydrolase domain containing (ABHD)6 and
      ABHD12 remain poorly characterized. By applying a sensitive fluorescent glycerol
      assay, we delineate the substrate preferences of human ABHD6 and ABHD12 in
      comparison with MAGL. We show that the three hydrolases are genuine MAG lipases;
      medium-chain saturated MAGs were the best substrates for hABHD6 and hMAGL,
      whereas hABHD12 preferred the 1 (3)- and 2-isomers of arachidonoylglycerol. Site
      directed mutagenesis of the amino acid residues forming the postulated catalytic
      triad (ABHD6: S148-D278-H306, ABHD12: S246-D333-H372) abolished enzymatic
      activity as well as labeling with the active site serine-directed
      fluorophosphonate probe TAMRA-FP. However, the role of D278 and H306 as residues
      of the catalytic core of ABHD6 could not be verified because none of the mutants
      showed detectable expression. Inhibitor profiling revealed striking potency
      differences between hABHD6 and hABHD12, a finding that, when combined with the
      substrate profiling data, should facilitate further efforts toward the design of
      potent and selective inhibitors, especially those targeting hABHD12, which
      currently lacks such inhibitors.

PMID- 22969152
TI  - Regulation of the human prostacyclin receptor gene by the cholesterol-responsive
      SREBP1.
AB  - Prostacyclin and its prostacyclin receptor, the I Prostanoid (IP), play essential
      roles in regulating hemostasis and vascular tone and have been implicated in a
      range cardio-protective effects but through largely unknown mechanisms. In this
      study, the influence of cholesterol on human IP [(h)IP] gene expression was
      investigated in cultured vascular endothelial and platelet-progenitor
      megakaryocytic cells. Cholesterol depletion increased human prostacyclin receptor
      (hIP) mRNA, hIP promoter-directed reporter gene expression, and hIP-induced cAMP
      generation in all cell types. Furthermore, the constitutively active sterol
      response element binding protein (SREBP)1a, but not SREBP2, increased hIP mRNA
      and promoter-directed gene expression, and deletional and mutational analysis
      uncovered an evolutionary conserved sterol-response element (SRE), adjacent to a
      known functional Sp1 element, within the core hIP promoter. Moreover, chromatin
      immunoprecipitation assays confirmed direct cholesterol-regulated binding of
      SREBP1a to this hIP promoter region in vivo, and immunofluorescence microscopy
      corroborated that cholesterol depletion significantly increases hIP expression
      levels. In conclusion, the hIP gene is directly regulated by cholesterol
      depletion, which occurs through binding of SREBP1a to a functional SRE within its
      core promoter. Mechanistically, these data establish that cholesterol can
      regulate hIP expression, which may, at least in part, account for the combined
      cardio-protective actions of low serum cholesterol through its regulation of IP
      expression within the human vasculature.

PMID- 22969154
TI  - Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E
      status in tocopherol supplemented mice and reveals extra-hepatic vitamin E
      metabolism.
AB  - The widely conserved preferential accumulation of alpha-tocopherol (alpha-TOH) in
      tissues occurs, in part, from selective postabsorptive catabolism of non-alpha
      TOH forms via the vitamin E-omega-oxidation pathway. We previously showed that
      global disruption of CYP4F14, the major but not the only mouse TOH-omega
      hydroxylase, resulted in hyper-accumulation of gamma-TOH in mice fed a soybean
      oil diet. In the current study, supplementation of Cyp4f14(-/-) mice with high
      levels of delta- and gamma-TOH exacerbated tissue enrichment of these forms of
      vitamin E. However, at high dietary levels of TOH, mechanisms other than omega
      hydroxylation dominate in resisting diet-induced accumulation of non-alpha-TOH.
      These include TOH metabolism via omega-1/omega-2 oxidation and fecal elimination
      of unmetabolized TOH. The omega-1 and omega-2 fecal metabolites of gamma- and
      alpha-TOH were observed in human fecal material. Mice lacking all liver
      microsomal CYP activity due to disruption of cytochrome P450 reductase revealed
      the presence of extra-hepatic omega-, omega-1, and omega-2 TOH hydroxylase
      activities. TOH-omega-hydroxylase activity was exhibited by microsomes from mouse
      and human small intestine; murine activity was entirely due to CYP4F14. These
      findings shed new light on the role of TOH-omega-hydroxylase activity and other
      mechanisms in resisting diet-induced accumulation of tissue TOH and further
      characterize vitamin E metabolism in mice and humans.

PMID- 22969155
TI  - Gossypiboma as an unusual cause of altered bowel habit.

PMID- 22969153
TI  - Differential expression of oxidation-specific epitopes and apolipoprotein(a) in
      progressing and ruptured human coronary and carotid atherosclerotic lesions.
AB  - The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a)
      [Lp(a)] and progressive atherosclerosis and plaque rupture have not been
      determined. Coronary artery sections from sudden death victims and carotid
      endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids
      (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected
      by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid
      and saphenous vein graft distal protection devices was determined with LC-MS/MS.
      In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and
      minimally present in early lesions. As lesions progressed, apoB and MDA epitopes
      did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased
      proportionally, but they differed according to plaque type and plaque components.
      Apo(a) epitopes were present throughout early and late lesions, especially in
      macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late
      lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they
      were most specifically associated with unstable and ruptured plaques. Specific
      OxPL were present in distal protection devices. Human atherosclerotic lesions
      manifest a differential expression of OSEs and apo(a) as they progress, rupture,
      and become clinically symptomatic. These findings provide a rationale for
      targeting OSE for biotheranostic applications in humans.

PMID- 22969156
TI  - Liver abscess caused by toothpick and treated by laparoscopic left hepatic
      resection: case report and literature review.
AB  - Hepatic abscesses caused by ingested foreign bodies have been reported in the
      medical literature but represent very uncommon events. Extra-luminal migration of
      sawing needles and pins is the most common cause of perforation of the
      gastrointestinal tract associated with liver infections. Other non-metallic sharp
      objects such as animal bones and toothpicks have been described but are less
      frequent. The authors present a case of a 45-year-old woman who suffered from
      sepsis and a liver abscess because of the migration of a toothpick that lodged in
      the left hepatic lobe. Review of the literature on the pathogenesis and clinical
      management of liver abscesses caused by ingested foreign is presented.

PMID- 22969157
TI  - Revisiting the nucleolus: from marker to dynamic integrator of cancer signaling.
AB  - Key signaling pathways (such as phosphoinositide 3-kinase, Myc, and RAS) act as
      sensors of energy, stress, and nutrient availability and integrate these inputs
      to directly control ribosome production and gene expression at the translational
      level. This activity is normally directly coupled to cell growth, division, and
      survival. However, it remains poorly understood the extent to which changes in
      ribosome number and nucleolar integrity downstream of these key signaling
      pathways contribute to their oncogenic activity. Emerging studies provide
      interesting insight into how deregulations in RNA polymerase I activity may lead
      to tumorigenesis and suggest that new drugs targeting ribosomal DNA transcription
      may hold great promise for the treatment of cancer.

PMID- 22969159
TI  - The membrane-bound enzyme CD38 exists in two opposing orientations.
AB  - The transmembrane enzyme CD38, a multifunctional protein ubiquitously present in
      cells, is the main enzyme that synthesizes and hydrolyzes cyclic adenosine 5'
      diphosphate-ribose (cADPR), an intracellular Ca(2+)-mobilizing messenger. CD38 is
      thought to be a type II transmembrane protein with its carboxyl-terminal
      catalytic domain located on the outside of the cell; thus, the mechanism by which
      CD38 metabolizes intracellular cADPR has been controversial. We developed
      specific antibodies against the amino-terminal segment of CD38 and showed that
      two opposing orientations of CD38, type II and type III (which has its catalytic
      domain inside the cell), were both present on the surface of HL-60 cells during
      retinoic acid-induced differentiation. When activated by interferon-gamma, human
      primary monocytes and the monocytic U937 cell line exhibited a similar co
      distribution pattern. Site-directed mutagenesis experiments showed that the
      membrane orientation of CD38 could be converted from a mixture of type II and
      type III orientations to all type III by mutating the cationic amino acid
      residues in the amino-terminal segment of CD38. Expression of type III CD38
      construct in transfected cells led to increased intracellular concentrations of
      cADPR, indicating the importance of the type III orientation of CD38 to its
      Ca(2+) signaling function. The identification of these two forms of CD38 suggests
      that flipping the catalytic domain from the outside to the inside of the cell may
      be a mechanism regulating its signaling activity.

PMID- 22969160
TI  - Coronary artery calcification progression in asymptomatic individuals with
      initial score of zero.
AB  - The aim of this study is to determine the progression of coronary artery
      calcification (CAC) using electron beam computed tomography (CT) when the initial
      CAC score (CACS) is zero and to determine the best interval to repeat a CAC scan.
      We studied 388 individuals with zero CACS (308 males; mean age: 48.8 +/- 8.26
      years) who underwent 2 consecutive CT scans in a period of at least 12 months
      apart. The interscan period was 2.99 +/- 1.35 years (range: 1-6 years). Three
      quarters of the individuals (75%) did not develop any CAC progression, 20.87%
      presented CAC progression of 1 to 10, 3.6% had 11 to 50, whereas only 0.51% had
      >50. The average time of new CAC development was 4.2 +/- 1.1 years. Individuals
      with CAC progression presented higher incidence of hypertension, diabetes
      mellitus, hypercholesterolaemia and higer frequency of male gender than those
      with without CAC changes (p<0.02). No cardiac events occurred during the follow
      up period.

PMID- 22969158
TI  - Network analysis of the focal adhesion to invadopodia transition identifies a
      PI3K-PKCalpha invasive signaling axis.
AB  - In cancer, deregulated signaling can produce an invasive cellular phenotype. We
      modeled the invasive transition as a theoretical switch between two cytoskeletal
      structures: focal adhesions and extracellular matrix-degrading invadopodia. We
      constructed molecular interaction networks of each structure and identified
      upstream regulatory hubs through computational analyses. We compared these
      regulatory hubs to the status of signaling components from head and neck
      carcinomas, which led us to analyze phosphatidylinositol 3-kinase (PI3K) and
      protein kinase C alpha (PKCalpha). Consistent with previous studies, PI3K
      activity promoted both the formation and the activity of invadopodia. We found
      that PI3K induction of invadopodia was increased by overexpression of SH2 (Src
      homology 2) domain-containing inositol 5'-phosphatase 2 (SHIP2), which converts
      the phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] that is produced by
      PI3K activity to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)], which is
      believed to promote invadopodia formation. Knockdown of PKCalpha had divergent
      effects on invadopodia formation, depending on the status of PI3K. Loss of
      PKCalpha inhibited invadopodia formation in cells with wild-type PI3K pathway
      status. Conversely, in cells with constitutively active PI3K (through activating
      PI3K mutants or lacking the endogenous opposing enzyme PTEN), PKCalpha knockdown
      increased invadopodia formation. Mechanistic studies revealed a negative feedback
      loop from PKCalpha that dampened PI3K activity and invasive behavior in cells
      with genetic hyperactivation of the PI3K pathway. These studies demonstrated the
      potential of network modeling as a discovery tool and identified PI3K and
      PKCalpha as interacting regulators of invasive behavior.

PMID- 22969161
TI  - Plasma matrix metalloproteinase 9 levels may predict endoleaks after endovascular
      aortic aneurysm repair.
AB  - A simple, noninvasive and cost-effective diagnostic test for the detection of
      endoleaks after endovascular aneurysm repair (EVAR) would complement (or even
      replace) current surveillance modalities. We reviewed the literature for studies
      correlating circulating levels of matrix metalloproteinases (MMPs)/tissue
      inhibitors of MMPs with the presence of endoleaks after EVAR. An electronic
      search of databases was performed to identify studies reporting circulating
      concentrations of MMPs in patients with and without an endoleak after EVAR. Four
      studies were identified. Patients with an endoleak had higher plasma MMP-9 levels
      compared with those without an endoleak. Two studies that also evaluated plasma
      MMP-3 levels after EVAR suggest that these levels may also be higher in patients
      with an endoleak. Preliminary evidence suggests that MMP-9 levels are increased
      in patients developing an endoleak after EVAR. Larger studies are required to
      confirm or refute our findings.

PMID- 22969162
TI  - Renalase, hypertension, and kidney - the discussion continues.
AB  - Hypertension and cardiovascular complications are very common in chronic kidney
      disease (CKD). Overactivation of sympathetic nervous system is also widely
      recognized in CKD. Renalase may play an important role in the control of blood
      pressure (BP) by its regulatory function of catecholamine metabolism. Renalase
      could be synthesized not only by the kidney but also by cardiomyocytes, liver,
      and adipose tissue. It probably exerts a hypotensive action, at least in animal
      models. Whether it metabolizes catecholamines remains to be proved. Another issue
      that remains to be resolved is the relationship between renalase and renal
      natriuresis and phosphaturia. In this review, the updated experimental and
      clinical data on renalase are presented and possible interactions with the
      endothelium are discussed. Renalase is "a new postulated therapeutic target."
      Proof of concept studies are needed to define the pathophysiological link between
      the kidney, sympathetic tone, BP, and cardiovascular complications.

PMID- 22969163
TI  - Perceived stress and vascular disease: where are we now?
AB  - Apart from traditional risk factors, psychosocial characteristics are
      increasingly considered as potential predictors of cardiovascular disease (CVD).
      The concept of stress is relevant when discussing the relationship between
      psychosocial factors and CVD. Among stress types and definitions (ie, marital
      stress, work stress), "perceived stress" presents a global and comprehensive
      stress construct and is based on the concept that individuals actively interact
      with their environment, appraising potentially threatening or challenging events
      in the light of available coping resources. However, the role of perceived stress
      in CVD incidence has not yet been completely elucidated. Thus, we evaluate
      perceived stress as a CVD risk factor by reviewing the literature. We also
      discuss the relationship between negative affect and CVD development. 

PMID- 22969164
TI  - Still radical after all these years: George Kelly's The psychology of personal
      constructs.
AB  - George Kelly's "The psychology of personal constructs" put forward a new
      psychology that viewed people as actively constructing and anticipating their
      worlds. This paper considers personal construct theory and its philosophy;
      personal construct assessment techniques; the personal construct view of
      psychological disorder and its treatment; and the wide range of other
      applications of personal construct theory. It is concluded that personal
      construct psychology remains a radical approach over half a century after Kelly
      published his magnum opus.

PMID- 22969165
TI  - Connecting body and mind: the first interview with somatising patients and their
      families.
AB  - In this article we outline the framework our consultation-liaison team has
      developed for interviewing families whose children present with medically
      unexplained symptoms. The framework was developed over many years in the context
      of our work with a large number of families, who collectively taught us to be
      more sensitive with regard to the experience of such families in the medical
      system, and who reacted strongly when we moved prematurely to the use of
      psychological language or to questions about family relationships or emotional
      functioning. Throughout the interview we maintain a focus on the body: the family
      history of illness and, in particular, the story of the child's symptoms. We take
      a detailed, temporally ordered history of the symptom and ask for collateral
      information - family illness, family life events, events at school, family
      emotional responses - all in relation to the story of the symptoms. In the
      assessment interview and in our work in general, we focus on the body. We move
      very carefully and very slowly from the physical to the psychological, from
      talking about the body to talking about relationships and about the mind.

PMID- 22969166
TI  - Concurrent Cognitive Processes in Rat Serial Pattern Learning: Item Memory,
      Serial Position, and Pattern Structure.
AB  - Three experiments examined the processes mediating rat serial pattern learning
      for rule-consistent versus rule-violating pattern elements ("violation
      elements"). In all three experiments, rats were trained to press retractable
      levers in a circular array in a specific sequence for brain stimulation reward
      (BSR). Experiment 1 examined the role of lever location (L) and element serial
      position (SP) cues in rats' ability to learn to anticipate a violation element
      positioned at the end of a 24-element serial pattern. Rats with L cues either
      alone or in combination with SP cues learned to anticipate the violation element,
      whereas those with SP cues alone did not. Rats in groups L and L+SP underwent a
      series of transfers designed to remove various cues that might have controlled
      their performance on the violation element. Results indicated that intra-chamber
      lever location cues mediated performance on the violation element whereas
      performance on rule-consistent elements within pattern chunks was mediated by an
      internal mnemonic representation that was insensitive to changes in lever
      location cues. Experiment 2 examined whether rats could learn to use SP cues
      alone to anticipate a violation element if it was positioned earlier in a serial
      pattern. Rats learned to anticipate the violation element based on SP cues alone
      when it was located in SP6 in a 24-element pattern, but not when it was in SP12.
      Experiment 3 examined whether or not rats spontaneously encode information about
      chunk length and the serial position of phrasing cues in serial patterns. Rats
      were trained to a high criterion on the serial pattern used in Experiment 1, then
      were challenged with three probe patterns that manipulated both chunk length and
      overall pattern length. Results indicated that rats spontaneously encoded
      information regarding the serial position of phrasing cues in relation to chunk
      length. Thus, rats appear to use at least three cognitive processes concurrently
      in serial pattern learning tasks, namely, item memory involving external
      discriminative cues, counting- or timing-like processes for encoding serial
      position, and rule abstraction for encoding an internal representation of pattern
      structure.

PMID- 22969167
TI  - Respondent-Driven Sampling: An Assessment of Current Methodology.
AB  - Respondent-Driven Sampling (RDS) employs a variant of a link-tracing network
      sampling strategy to collect data from hard-to-reach populations. By tracing the
      links in the underlying social network, the process exploits the social structure
      to expand the sample and reduce its dependence on the initial (convenience)
      sample.The current estimators of population averages make strong assumptions in
      order to treat the data as a probability sample. We evaluate three critical
      sensitivities of the estimators: to bias induced by the initial sample, to
      uncontrollable features of respondent behavior, and to the without-replacement
      structure of sampling.Our analysis indicates: (1) that the convenience sample of
      seeds can induce bias, and the number of sample waves typically used in RDS is
      likely insufficient for the type of nodal mixing required to obtain the reputed
      asymptotic unbiasedness; (2) that preferential referral behavior by respondents
      leads to bias; (3) that when a substantial fraction of the target population is
      sampled the current estimators can have substantial bias.This paper sounds a
      cautionary note for the users of RDS. While current RDS methodology is powerful
      and clever, the favorable statistical properties claimed for the current
      estimates are shown to be heavily dependent on often unrealistic assumptions. We
      recommend ways to improve the methodology.

PMID- 22969169
TI  - Association between serum neopterin and inflammatory activation in chronic kidney
      disease.
AB  - BACKGROUND: The serum levels of neopterin, a marker associated with cell-mediated
      immunity are elevated in chronic kidney disease (CKD). We evaluated serum
      neopterin levels and investigated its association with markers of inflammation in
      a cross-section of CKD subjects without known cardiovascular disease. METHODS:
      Serum neopterin levels were measured in 118 patients with stage 3-5 CKD and 41
      healthy subjects with normal kidney function (HC). Patients with known
      cardiovascular disease were excluded. We also estimated highly sensitive CRP
      (hsCRP) and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma) in the CKD subjects. All assays were done using
      commercially available ELISA kits. The correlation between neopterin and markers
      of inflammation were investigated. RESULTS: Of the CKD population, 82 were in
      stage 5 (60 stage 5 D), 24 in stage 4, and 12 in stage 3. The mean age was 51.04
      +/- 1.3 years and 66% were males. The commonest cause of CKD was diabetes (36%).
      Serum neopterin levels were 5-fold higher in CKD patients as compared to HC (74.8
      +/- 3.6 versus 15.0 +/- 2.8 nmol/L, P < 0.0001). There was a graded increase of
      serum neopterin from stages 3 to 4 and 5. CKD 5 D patients exhibited
      significantly higher levels compared to nondialysis stage 5 patients (P <
      0.0001). An inverse correlation was noted between serum neopterin and eGFR (r = 
      0.359, P < 0.0001). Serum neopterin correlated with hsCRP (r = 0.285, P = 0.002),
      IL-6 (r = 0.212, P = 0.034), and IFN-gamma (r = 0.32, P = 0.001) but not with TNF
      alpha. CONCLUSION: Serum neopterin level is elevated and correlates with the
      severity of CKD. The elevation correlates with elevation of most, but not all,
      inflammatory markers. Its role in future development of cardiovascular disease
      and modulation with anti-inflammatory therapies needs further studies.

PMID- 22969168
TI  - Inflammation in diabetic nephropathy.
AB  - Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide
      but current treatments remain suboptimal. This review examines the evidence for
      inflammation in the development and progression of diabetic nephropathy in both
      experimental and human diabetes, and provides an update on recent novel
      experimental approaches targeting inflammation and the lessons we have learned
      from these approaches. We highlight the important role of inflammatory cells in
      the kidney, particularly infiltrating macrophages, T-lymphocytes and the
      subpopulation of regulatory T cells. The possible link between immune deposition
      and diabetic nephropathy is explored, along with the recently described immune
      complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some
      of the major inflammatory cytokines involved in the pathogenesis of diabetic
      nephropathy, including the role of adipokines. Lastly, we present the latest data
      on the pathogenic role of the stress-activated protein kinases in diabetic
      nephropathy, from studies on the p38 mitogen activated protein kinase and the c
      Jun amino terminal kinase cell signalling pathways. The genetic and
      pharmacological approaches which reduce inflammation in diabetic nephropathy have
      not only enhanced our understanding of the pathophysiology of the disease but
      shown promise as potential therapeutic strategies.

PMID- 22969170
TI  - Prevention of LPS-induced acute lung injury in mice by progranulin.
AB  - The acute respiratory distress syndrome (ARDS), a clinical complication of severe
      acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality
      in critically ill patients. Despite decades of research, few therapeutic
      strategies for clinical ARDS have emerged. Here we carefully evaluated the effect
      of progranulin (PGRN) in treatment of ARDS using the murine model of
      lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN
      maintained the body weight and survival of ALI mice. We revealed that
      administration of PGRN significantly reduced LPS-induced pulmonary inflammation,
      as reflected by reductions in total cell and neutrophil counts, proinflammatory
      cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid.
      Furthermore, administration of PGRN resulted in remarkable reversal of LPS
      induced increases in lung permeability as assessed by reductions in total
      protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant
      reduction of histopathology changes of lung in mice received PGRN treatment.
      Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective
      effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that
      PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a
      potential application for PGRN-based therapy to treat clinical ARDS.

PMID- 22969172
TI  - Child labour issues and challenges.

PMID- 22969171
TI  - Macrolide therapy in chronic inflammatory diseases.
AB  - Macrolides are a group of antibiotics with a distinctive macrocyclic lactone ring
      combined with sugars (cladinose, desosamine). The action of macrolides is to
      block protein synthesis by binding to the subunit of 50S ribosome of bacteria.
      Prototype macrolide was erythromycin, which came into clinical practice in the
      50s of the 20th century. Its antimicrobial spectrum covers the scope of the
      penicillins but is extended to the impact of atypical bacteria. In the 90 s more
      drugs of this group were synthesized-they have less severe side effects than
      erythromycin, extended spectrum of Gram-negative bacteria. Macrolides are
      effective in treating mycobacterial infections especially in patients infected
      with HIV. It is now known that in addition to antibacterial abilities, macrolides
      have immunomodulatory effects-they inhibit the production of proinflammatory
      cytokines (TNF, IL1, 6, and 8) affect transcription factors (NF-kappaB) as well
      as costimulaton (CD 80) and adhesion molecules (ICAM). This review article
      focused not only on the their antimicrobial abilities but also on efficacy in the
      treatment of several inflammatory disorders independent of the infectious agent.
      Their wider use as immunomodulators requires further study, which can lead to an
      extension of indications for their administration.

PMID- 22969173
TI  - Gender differences in stress response: Role of developmental and biological
      determinants.
AB  - Stress response is associated with manifestations of various psychosomatic and
      psychiatric disorders. Hence, it is important to understand the underlying
      mechanisms that influence this association. Moreover, men and women tend to react
      differently with stress-both psychologically and biologically. These differences
      also need to be studied in order to have a better understanding in the gender
      difference observed for many disorders, which are likely to be contributed by the
      gender difference in stress reactivity and responses. Such an understanding would
      have a significant impact on our understanding about how adult health is set
      during early life and how adult disease could be prevented in men and women.

PMID- 22969174
TI  - Sociodemographic profile, clinical factors, and mode of attempt in suicide
      attempters in consultation liaison psychiatry in a tertiary care center.
AB  - BACKGROUND: The objective was to study the sociodemographic data, psychiatric
      disorder, precipitating events, and mode of attempt in suicide attempted patients
      referred to consultation liaison psychiatric services. SETTINGS AND DESIGN: A
      prospective study of 6-month duration was done in a tertiary care center in
      India. MATERIALS AND METHODS: During the 6-month period all referrals were
      screened for the presence of suicide attempters in consultation liaison services.
      Those who fulfilled the criteria for suicide attempters were evaluated by using
      semistructured pro forma containing sociodemographic data, precipitating events,
      mode of attempt, and psychiatric diagnosis by using ICD-10. RESULTS: The male-to
      female ratio was similar. Adult age, urban background, employed, matriculation
      educated were more represented in this study. More than 80% of all attempters had
      psychiatric disorder. Majority had a precipitating event prior to suicide
      attempt. The most common method of attempt was by use of corrosive. CONCLUSIONS:
      Majority of suicide attempter patients had mental illness. Early identification
      and treatment of these disorders would have prevented morbidity and mortality
      associated with this. There is a need of proper education of relatives about
      keeping corrosive and other poisonous material away from patients as it was being
      commonest mode of attempt.

PMID- 22969175
TI  - Attitude toward mental illness amongst urban nonpsychiatric health professionals.
AB  - BACKGROUND: This study was designed to examine the attitude of nonpsychiatric
      health professionals about mental illness in urban multispeciality tertiary care
      setting. AIM: To assess attitude toward mental illness among urban nonpsychiatric
      health professionals. MATERIALS AND METHODS: A cross-sectional study design was
      used. A pretested, semistructured questionnaire was administered to 222 medical
      and paramedical staff at two tertiary care hospitals at Chandigarh. RESULTS:
      There is an increased awareness of mental illness especially in military
      subjects. Literacy was associated with a positive attitude toward mental illness.
      Health care givers commonly fail to ask about the emotional well being of their
      patients. Many saw referral to psychiatrist as a form of punishment. There is
      uniform desire for more knowledge about psychiatric disorders in medical and
      paramedical staff. CONCLUSIONS: This study demonstrates the need for educational
      programs aimed at demystifying mental illness. A better understanding of mental
      disorders among the nonpsychiatric medical professional would help to allay fear
      and mistrust about mentally ill persons in the community as well as lessen
      stigmatization toward such persons.

PMID- 22969176
TI  - Gender differences in perception of workplace sexual harassment among future
      professionals.
AB  - BACKGROUND: Indian society is in a stage of rapid social transition. As more
      women enter the workforce, stresses vis-a-vis the genders are to be expected in
      patriarchal society to which most of our population belongs. Earlier studies in
      Western societies have revealed gender differences in perception of what
      constitutes sexual harassment. AIM: Elicit gender differences, if any, in the
      workplace sexual harassment among future professionals. SETTINGS AND DESIGN: A
      cross-sectional study among the students of professional colleges. MATERIALS AND
      METHODS: A total of 200 students of both sexes were randomly selected from four
      professional colleges. Data collection was done on a structured questionnaire by
      interview. STATISTICAL ANALYSIS: Internal consistency of the questionnaire was
      tested by Crohnbach's alpha coefficient. Associations between gender and
      perceptions were explored with Chi-square, Odds Ratio with 95% confidence
      interval, where applicable. RESULTS: The differences in perception on what
      constitutes sexual harassment among the genders were statistically significant on
      many measures (P<0.01). CONCLUSIONS: Men and women differ in their awareness as
      to what constitute sexual harassment. Men were more lacking in awareness
      regarding sexual harassment.

PMID- 22969177
TI  - Tolerability and efficacy of paliperidone ER compared to olanzapine in the
      treatment of schizophrenia: A randomized, double-blind, multicentric trial.
AB  - BACKGROUND: Paliperidone is an active metabolite of risperidone and actss through
      a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A)
      receptor antagonism. AIM: The present randomized, double-blind, multicentric
      trial was designed to determine the safety and efficacy of paliperidone extended
      release (ER) compared to olanzapine in the treatment of acute schizophrenia.
      MATERIALS AND METHODS: A total of 214 patients with diagnosis of schizophrenia
      were randomized to paliperidone ER (n=109) and olanzapine (n=106) treatment
      groups. Totally 206 patients were evaluated for efficacy parameters using
      Positive and negative syndrome scale (PANSS) score and Clinical Global Impression
      severity of illness (CGI-S) and Clinical Global Impression-improvement of illness
      (CGI-I) scales. Safety was assessed by treatment-emergent adverse events and
      movement disorders. RESULTS: All patients showed significant reduction in PANSS
      scores at the end of treatment. However, the results were comparable and there
      was no significant difference at the end of the trial between paliperidone ER
      group and olanzapine group. Both the treatment groups showed decrease in the
      severity of illness and improvement in symptomatology. The most common adverse
      events reported in paliperidone ER versus olanzapine group were Extra Pyramidal
      Syndrome (EPS) (13.7% vs. 15.6%), headache (12.7% vs. 8.9%), increased appetite
      (8.8% vs. 10.0%) and drowsiness (4.9% vs. 303%). There was no clinically relevant
      difference in change from baseline to the end of the trial in abnormal
      involuntary movement scale (AIMS) and barnes akathisia rating scale (BARS) total
      scores between both the groups. CONCLUSION: Paliperidone ER is effective in
      controlling schizophrenic symptoms as well as exhibits comparable tolerability
      profile. Thus, paliperidone ER has the potential to be a useful new treatment
      option for patients with schizophrenia.

PMID- 22969178
TI  - Individual differences in hemispheric preference and emotion regulation
      difficulties.
AB  - BACKGROUND: Hemisphericity or individual difference in the preference to use the
      left or the right hemispheric mode of information processing has been associated
      with various emotion-related differences. For example, the right hemisphericity
      has been linked with inhibition of emotional expression, feeling of tension,
      greater impulsivity etc. These observations suggest that right hemisphericity may
      be associated with greater difficulties in regulating emotions. However, direct
      empirical tests of such theoretical proposition are very thin. AIM: In view of
      this, the present study aims to investigate how and to what extent individual
      difference in hemispheric preference relate to emotion regulation. MATERIALS AND
      METHODS: Thirty-two right-handed male subjects in the age range 18 to 20 years
      were assessed on self-report measures of hemispheric preference and emotion
      regulation difficulties. The correlation between dimensions of hemispheric
      preference and difficulties in regulating emotions was computed. A series of
      stepwise multiple regression analyses were also done to explore the relative
      significance of various dimensions of hemispheric preference in predicting
      emotion regulation difficulties. RESULTS: The findings revealed that in general a
      preference for the right hemispheric mode of information processing was
      associated with greater emotion regulation difficulties. The correlation analysis
      indicated that while impulse control difficulties and difficulties in engaging
      goal directed behavior was associated with preference for almost all the right
      hemispheric mode of information processing, the nonacceptance of emotional
      responses and limited access to emotion regulation was related to preference for
      only global/synthetic (a right hemispheric) mode of information processing.
      Similarly, the lack of emotional clarity facet of emotion regulation difficulties
      correlated significantly with a preference for the emotional mode of information
      processing (again a right hemispheric mode). The results of stepwise multiple
      regression analyses, however, indicated that "nonacceptance of emotional
      responses' and 'limited access to emotion regulation strategies" facets of
      emotion regulation difficulties were best predicted by a preference for the
      global/synthetic mode of information processing. While others like difficulties
      engaging in goal-directed behaviour, impulse control difficulties, and lack of
      emotional clarity were best predicted by a preference for visuo-spatial rather
      than the verbal mode of information processing. CONCLUSION: Overall, the findings
      imply that greater preference for right hemispheric mode of information
      processing as compared to the left is associated with greater difficulties in
      regulating emotions.

PMID- 22969179
TI  - Emotional intelligence scale for medical students.
AB  - BACKGROUND: Emotional Intelligence has been associated with positive outcome
      process in varied professions. There is paucity of Indian literature on the
      subject; especially involving medical undergraduates; and presently there is no
      scale available to measure the same in the Indian scenario. OBJECTIVE: To develop
      a scale to measure Emotional Intelligence among medical undergraduates. MATERIALS
      AND METHODS: Four domains of Emotional intelligence were selected, viz. Self
      Awareness, Self-Management, Social-Awareness & Social-Skills and these were
      included for the purpose of domains of the scale. On the basis of focused group
      discussions and in-depth deliberations with experts, undergraduate and
      postgraduate medical students a pool of 50 items was generated. The items were
      reduced to 27 based on expert consensus and on the basis of frequency of
      endorsement by expert reviews. It was followed by a pilot study of 50
      undergraduates. This completed the preparation of the preliminary draft based on
      content analysis. The questionnaire was then administered in 480 students and the
      data was analyzed by appropriate statistical methods. For the purpose of
      concurrent validity, emotional intelligence scale developed by Dr. Ekta was used.
      RESULTS: The Cronbach's Alpha for Internal Consistency Reliability was 0.68. The
      EIS had a significant correlation with social awareness domain of Emotional
      Intelligence Test (EIT) establishing Concurrent Validity. CONCLUSION: Emotional
      Intelligence Scale for medical undergraduates was constructed. Reliability and
      concurrent validity were also established for the same.

PMID- 22969180
TI  - Integrated yoga therapy for improving mental health in managers.
AB  - BACKGROUND: Managers' lives have become a never-ending race against time,
      technology, and targets. This race creates tension, which leads to
      dissatisfaction and frustration and eventually manifests itself as psychological
      and physiological stress with mental and emotional drain. This modern lifestyle
      intensifies the stress leading to "Excessive Tension" and consequent
      deterioration in "Executive Efficiency." OBJECTIVE: To assess mental health in
      managers undergoing yoga-based Self-Management of Excessive Tension (SMET)
      program. MATERIALS AND METHODS: 72 managers with 48.75+/-3.86 years of mean age
      were participated in this study of single group pre-post design. The General
      Health Questionnaire data were taken on the first and sixth day of 5 days SMET
      program. RESULTS: The data analysis showed 68.25% decrease (P<0.001) in somatic
      symptoms, 66.29% decrease (P<0.001) in anxiety and insomnia, 65.00% decrease
      (P<0.001) in social dysfunction, 87.08% decrease (P<0.001) in severe depression,
      and 71.47% decrease (P<0.001) in all medical complaints. CONCLUSION: These
      results suggest that participation in a SMET program was associated with
      improvement in mental health and may have implications for "Executive
      Efficiency."

PMID- 22969181
TI  - Understanding sexuality among Indian urban school adolescents.
AB  - CONTEXT: Adolescence is a very exciting phase of life fraught with many
      challenges like sexuality. Understanding them is important in helping the
      adolescents grow up healthily. AIMS: To ascertain the attitudes and knowledge
      about sexuality among school-going adolescents. SETTINGS AND DESIGN: Students in
      two urban schools of an Indian city from class IX to XII were administered a self
      reporting questionnaire on matters related to sexuality. MATERIALS AND METHODS:
      Requisite ethical clearances were taken as also the consent of the parents and
      students before administration of the questionnaire. The authors clarified doubts
      to adolescents. STATISTICAL ANALYSIS: Statistical package for social sciences.
      RESULTS: The incidence of having sexual contact was 30.08% for boys and 17.18%
      for girls. 6.31% boys and 1.31% girls reported having had experienced sexual
      intercourse. Friends constituted the main sexual partners for both boys and
      girls. Sexual abuse had been reported by both girls and boys. These and other
      findings are discussed in the article. CONCLUSIONS: Adolescent school students
      are involved in sexual activity, but lack adequate knowledge in this regard.
      Students, teachers, and parents need to understand various aspects of sexuality
      to be able to help adolescents' healthy sexual development.

PMID- 22969182
TI  - Mania in dengue fever.
AB  - Dengue fever, also known as break bone fever, is a mosquito-borne infection that
      causes a severe flu-like illness. During the last few years, there had been
      increasing reports of dengue fever with unusual manifestations, primarily with
      neurological symptoms. Psychiatric morbidity during acute dengue infection has
      rarely been reported. There has not been any systemic study mentioning the
      prevalence and pattern of psychiatric sequelae. We report a 28-year-old male who
      after an acute dengue infection developed an episode of mania which was
      successfully treated.

PMID- 22969183
TI  - An outbreak of Koro among 19 workers in a jute mill in south Bengal.
AB  - Koro is a culture-bound syndrome that is characterized by the belief of
      retraction of genitals into the abdomen. It was initially reported in Asian
      countries, as having a usual acute and brief course. Two case clusters have been
      described in this article. Both occurred in the same jute mill in southern West
      Bengal among the workers. The case clusters depict unique socioeconomic factors
      and interesting health-seeking behavior toward koro. All the cases had a self
      limiting course and reasonably good outcome. The case cluster yet again confirms
      that koro is not as rare as it is thought of and social and economic factors
      continue to play an important role in the etiology of the disease.

PMID- 22969184
TI  - Inhalant abuse: A cause for concern.
AB  - Inhalant abuse is of growing concern in adolescent and young adult population in
      the underdeveloped regions of the world. In the absence of availability of
      definitive tests in routine clinical settings, diagnosis is often difficult.
      Equally difficult is management and ensuring adherence to therapy. We report two
      successive cases of inhalant abuse seen at the outpatient department of the
      Department of Psychiatry, Mental Health Institute, SCB Medical College, Cuttack,
      Orissa, India. We report here two cases of inhalant abuse: one with an unusual
      mode of abuse and another with atypical clinical presentation.

PMID- 22969185
TI  - Delusional parasitosis of face in a factory worker.
AB  - Delusional parasitosis is a form of monohypochondriacal psychosis, a condition
      sometimes encountered in psychiatric or dermatological clinical practice. The
      exact etiology and outcome of this condition is not well known. A patient with
      delusional parasitosis of face who responded to aripiprazole is described.

PMID- 22969186
TI  - Tobacco-alcohol amblyopia: A rare complication of prolonged alcohol abuse.
AB  - Tobacco-alcohol amblyopia is rare, however, extremely disabling complication seen
      in patient with alcohol dependence syndrome, which if not addressed properly and
      at the right time may lead to persisting deficits. We here report a patient of
      alcohol-dependence syndrome who presented with significant diminution of vision
      bilaterally in the background of excess alcohol consumption.

PMID- 22969187
TI  - Pancreatico-biliary endoscopic ultrasound: a systematic review of the levels of
      evidence, performance and outcomes.
AB  - Our aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature
      of the past 3 decades and evaluate its role based on a critical appraisal of
      published studies according to levels of evidence (LE). Original research
      articles (randomized controlled trials, prospective and retrospective studies),
      meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were
      included. All articles published until September 2011 were retrieved from PubMed
      and classified according to specific disease entities, anatomical subdivisions
      and therapeutic applications of EUS. The North of England evidence-based
      guidelines were used to determine LE. A total of 1089 pertinent articles were
      reviewed. Published research focused primarily on solid pancreatic neoplasms,
      followed by disorders of the extrahepatic biliary tree, pancreatic cystic
      lesions, therapeutic-interventional EUS, chronic and acute pancreatitis. A
      uniform observation in all six categories of articles was the predominance of LE
      III studies followed by LE IV, II b, II a, I b and I a, in descending order. EUS
      remains the most accurate method for detecting small (< 3 cm) pancreatic tumors,
      ampullary neoplasms and small (< 4 mm) bile duct stones, and the best test to
      define vascular invasion in pancreatic and peri-ampullary neoplasms. Detailed EUS
      imaging, along with biochemical and molecular cyst fluid analysis, improve the
      differentiation of pancreatic cysts and help predict their malignant potential.
      Early diagnosis of chronic pancreatitis appears feasible and reliable. Novel
      imaging techniques (contrast-enhanced EUS, elastography) seem promising for the
      evaluation of pancreatic cancer and autoimmune pancreatitis. Therapeutic
      applications currently involve pancreaticobiliary drainage and targeted fine
      needle injection-guided antitumor therapy. Despite the ongoing development of
      extra-corporeal imaging modalities, such as computed tomography, magnetic
      resonance imaging, and positron emission tomography, EUS still holds a leading
      role in the investigation of the pancreaticobiliary area. The major challenge of
      EUS evolution is its expanding therapeutic potential towards an effective and
      minimally invasive management of complex pancreaticobiliary disorders.

PMID- 22969189
TI  - Colometer: a real-time quality feedback system for screening colonoscopy.
AB  - AIM: To investigate the performance of a new software-based colonoscopy quality
      assessment system. METHODS: The software-based system employs a novel image
      processing algorithm which detects the levels of image clarity, withdrawal
      velocity, and level of the bowel preparation in a real-time fashion from live
      video signal. Threshold levels of image blurriness and the withdrawal velocity
      below which the visualization could be considered adequate have initially been
      determined arbitrarily by review of sample colonoscopy videos by two experienced
      endoscopists. Subsequently, an overall colonoscopy quality rating was computed
      based on the percentage of the withdrawal time with adequate visualization
      (scored 1-5; 1, when the percentage was 1%-20%; 2, when the percentage was 21%
      40%, etc.). In order to test the proposed velocity and blurriness thresholds,
      screening colonoscopy withdrawal videos from a specialized ambulatory colon
      cancer screening center were collected, automatically processed and rated.
      Quality ratings on the withdrawal were compared to the insertion in the same
      patients. Then, 3 experienced endoscopists reviewed the collected videos in a
      blinded fashion and rated the overall quality of each withdrawal (scored 1-5; 1,
      poor; 3, average; 5, excellent) based on 3 major aspects: image quality, colon
      preparation, and withdrawal velocity. The automated quality ratings were compared
      to the averaged endoscopist quality ratings using Spearman correlation
      coefficient. RESULTS: Fourteen screening colonoscopies were assessed. Adenomatous
      polyps were detected in 4/14 (29%) of the collected colonoscopy video samples. As
      a proof of concept, the Colometer software rated colonoscope withdrawal as having
      better visualization than the insertion in the 10 videos which did not have any
      polyps (average percent time with adequate visualization: 79% +/- 5% for
      withdrawal and 50% +/- 14% for insertion, P < 0.01). Withdrawal times during
      which no polyps were removed ranged from 4-12 min. The median quality rating from
      the automated system and the reviewers was 3.45 [interquartile range (IQR), 3.1
      3.68] and 3.00 (IQR, 2.33-3.67) respectively for all colonoscopy video samples.
      The automated rating revealed a strong correlation with the reviewer's rating
      (rho coefficient= 0.65, P = 0.01). There was good correlation of the automated
      overall quality rating and the mean endoscopist withdrawal speed rating (Spearman
      r coefficient= 0.59, P = 0.03). There was no correlation of automated overall
      quality rating with mean endoscopists image quality rating (Spearman r
      coefficient= 0.41, P = 0.15). CONCLUSION: The results from a novel automated real
      time colonoscopy quality feedback system strongly agreed with the endoscopists'
      quality assessments. Further study is required to validate this approach.

PMID- 22969188
TI  - Gene expression profiling and endothelin in acute experimental pancreatitis.
AB  - AIM: To analyze gene expression profiles in an experimental pancreatitis and
      provide functional reversal of hypersensitivity with candidate gene endothelin-1
      antagonists. METHODS: Dibutyltin dichloride (DBTC) is a chemical used as a
      polyvinyl carbonate stabilizer/catalyzer, biocide in agriculture, antifouling
      agent in paint and fabric. DBTC induces an acute pancreatitis flare through
      generation of reactive oxygen species. Lewis-inbred rats received a single i.v.
      injection with either DBTC or vehicle. Spinal cord and dorsal root ganglia (DRG)
      were taken at the peak of inflammation and processed for transcriptional
      profiling with a cDNA microarray biased for rat brain-specific genes. In a second
      study, groups of animals with DBTC-induced pancreatitis were treated with
      endothelin (ET) receptor antagonists [ET-A (BQ123) and ET-B BQ788)]. Spontaneous
      pain related mechanical and thermal hypersensitivity were measured.
      Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on
      sections from pancreatic tissues and DRG of the T10-12 spinal segments. RESULTS:
      Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by
      pathological studies (edema in parenchyma, loss of pancreatic architecture and
      islets, infiltration of inflammatory cells, neutrophil and mononuclear cells,
      degeneration, vacuolization and necrosis of acinar cells) and the pain-related
      behaviors (cutaneous secondary mechanical and thermal hypersensitivity). Gene
      expression profile was different in the spinal cord from animals with
      pancreatitis compared to the vehicle control group. Over 260 up-regulated and 60
      down-regulated unique genes could be classified into 8 functional gene families:
      circulatory/acute phase/immunomodulatory; extracellular matrix; structural;
      channel/receptor/transporter; signaling transduction; transcription/translation
      related; antioxidants/chaperones/heat shock; pancreatic and other enzymes. ET-1
      was among the 52 candidate genes up-regulated greater than 2-fold in animals with
      pancreatic inflammation and visceral pain-related behavior. Treatments with the
      ET-A (BQ123) and ET-B (BQ-788) antagonists revealed significant protection
      against inflammatory pain related mechanical and thermal hypersensitivity
      behaviors in animals with pancreatitis (P < 0.05). Open field spontaneous
      behavioral activity (at baseline, day 6 and 30 min after drug treatments (BQ123,
      BQ788) showed overall stable activity levels indicating that the drugs produced
      no undesirable effects on normal exploratory behaviors, except for a trend toward
      reduction of the active time and increase in resting time at the highest dose
      (300 MUmol/L). Immunocytochemical localization revealed that expression of ET-A
      and ET-B receptors increased in DRG from animals with pancreatitis. Endothelin
      receptor localization was combined in dual staining with neuronal marker NeuN,
      and glia marker, glial fibrillary acidic protein. ET-A was expressed in the cell
      bodies and occasional nuclei of DRG neurons in naive animals. However, phenotypic
      expression of ET-A receptor was greatly increased in neurons of all sizes in
      animals with pancreatitis. Similarly, ET-B receptor was localized in neurons and
      in the satellite glia, as well as in the Schwann cell glial myelin sheaths
      surrounding the axons passing through the DRG. CONCLUSION: Endothelin-receptor
      antagonists protect against inflammatory pain responses without interfering with
      normal exploratory behaviors. Candidate genes can serve as future biomarkers for
      diagnosis and/or targeted gene therapy.

PMID- 22969190
TI  - Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis
      in experimental diversion colitis.
AB  - AIM: To investigate whether butyrate or glutamine enemas could diminish
      inflammation in experimental diversion colitis. METHODS: Wistar specific pathogen
      free rats were submitted to a Hartmann's end colostomy and treated with enemas
      containing glutamine, butyrate, or saline. Enemas were administered twice a week
      in the excluded segment of the colon from 4 to 12 wk after the surgical
      procedure. Follow-up colonoscopy was performed every 4 wk for 12 wk. The effect
      of treatment was evaluated using video-endoscopic and histologic scores and
      measuring interleukin-1beta, tumor necrosis factor-alpha, and transforming growth
      factor beta production in organ cultures by enzyme linked immunosorbent assay.
      RESULTS: Colonoscopies of the diverted segment showed mucosa with hyperemia,
      increased number of vessels, bleeding and mucus discharge. Treatment with either
      glutamine or butyrate induced significant reductions in both colonoscopic (P <
      0.02) and histological scores (P < 0.01) and restored the densities of collagen
      fibers in tissue (P = 0.015; P = 0.001), the number of goblet cells (P = 0.021; P
      = 0.029), and the rate of apoptosis within the epithelium (P = 0.043; P = 0.011)
      to normal values. The high levels of cytokines in colon explants from rats with
      diversion colitis significantly decreased to normal values after treatment with
      butyrate or glutamine. CONCLUSION: The improvement of experimental diversion
      colitis following glutamine or butyrate enemas highlights the importance of
      specific luminal nutrients in the homeostasis of the colonic mucosa and supports
      their utilization for the treatment of human diversion colitis.

PMID- 22969191
TI  - Adeno-associated virus mediated delivery of Tregitope 167 ameliorates
      experimental colitis.
AB  - AIM: To explore the anti-inflammatory potential of adeno-associated virus
      mediated delivery of Tregitope 167 in an experimental colitis model. METHODS: The
      trinitrobenzene sulfonate (TNBS) model of induced colitis was used in Balb/c
      mice. Subsequently after intravenous adeno-associated virus-mediated regulatory T
      cell epitopes (Tregitope) delivery, acute colitis was initiated by intra-rectal
      administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with
      TNBS (0.75 mg in 20% ethanol) 8 d later. Control groups included mice not treated
      with TNBS (healthy control group) and mice treated by TNBS only (diseased group).
      At the time of sacrifice colon weight, the disease activity index and histology
      damage score were determined. Immunohistochemical staining of the colonic tissues
      was performed to asses the cellular infiltrate and the presence of transcription
      factor forkhead Box-P3 (Foxp3). Thymus, mesenteric lymph nodes, liver and spleen
      tissue were collected and the corresponding lymphocyte populations were further
      assessed by flow cytometry analysis for the expression of CD4+ T cell and
      regulatory T cell associated markers. RESULTS: The Tregitope 167 treated mice
      gained an average of 4% over their initial body weight at the time of sacrifice.
      In contrast, the mice treated with TNBS alone (no Tregitope) developed colitis,
      and lost 4% of their initial body weight at the time of sacrifice (P < 0.01). The
      body weight increase that had been observed in the mice pre-treated with
      Tregitope 167 was substantiated by a lower disease activity index and a decreased
      colon weight as compared to the diseased control group (P < 0.01 and P < 0.001,
      respectively). Immunohistochemical staining of the colonic tissues for CD4+
      showed that inflammatory cell infiltrates were present in TNBS treated mice with
      or without administration with tregitope 167 and that these cellular infiltrates
      consisted mainly of CD4+ cells. For both TNBS treated groups CD4+ T cell
      infiltrates were observed in the sub-epithelial layer and the lamina propria.
      CD4+ T cell infiltrates were also present in the muscularis mucosa layer of the
      diseased control mice, but were absent in the Tregitope 167 treated group.
      Numerous Foxp3 positive cells were detected in the lamina propria and sub
      epithelium of the colon sections from mice treated with Tregitope 167.
      Furthermore, the Foxp3 and glycoprotein A repetitions predominant markers were
      significantly increased in the CD4+ T lymphocyte population in the thymus of the
      mice pre-treated with adeno-associated virus serotype 5 (cytomegalovirus promoter
      Tregitope 167), as cytomegalovirus promoter compared to lymphocyte populations in
      the thymus of diseased and the healthy control mice (P < 0.05 and P < 0.001,
      respectively). CONCLUSION: This study identifies adeno-associated virus-mediated
      delivery of regulatory T-cell epitope 167 as a novel anti-inflammatory approach
      with the capacity to decrease intestinal inflammation and induce long-term
      remission in inflammatory bowel disease.

PMID- 22969192
TI  - Results of National Colorectal Cancer Screening Program in Croatia (2007-2011).
AB  - AIM: To study the epidemiologic indicators of uptake and characteristic
      colonoscopic findings in the Croatian National Colorectal Cancer Screening
      Program. METHODS: Colorectal cancer (CRC) was the second leading cause of cancer
      mortality in men (n = 1063, 49.77/100,000), as well as women (n = 803,
      34.89/100,000) in Croatia in 2009. The Croatian National CRC Screening Program
      was established by the Ministry of Health and Social Welfare, and its
      implementation started in September, 2007. The coordinators were recruited in
      each county institute of public health with an obligation to provide fecal occult
      blood testing (FOBT) to the participants, followed by colonoscopy in all positive
      cases. The FOBT was performed by hypersensitive guaiac-based Hemognost card test
      (Biognost, Zagreb). The test and short questionnaire were delivered to the home
      addresses of all citizens aged 50-74 years consecutively during a 3-year period.
      Each participant was required to complete the questionnaire and send it together
      with the stool specimen on three test cards back to the institute for further
      analysis. About 4% FOBT positive cases are expected in normal risk populations. A
      descriptive analysis was performed. RESULTS: A total of 1,056,694 individuals
      (born between 1933-1945 and 1952-1957) were invited to screening by the end of
      September 2011. In total, 210,239 (19.9%) persons returned the envelope with a
      completed questionnaire, and 181,102 of them returned it with a correctly placed
      stool specimen on FOBT cards. Until now, 12,477 (6.9%), FOBT-positive patients
      have been found, which is at the upper limit of the expected values in European
      Guidelines for Quality Assurance in CRC Screening and Diagnosis [European Union
      (EU) Guidelines]. Colonoscopy was performed in 8541 cases (uptake 66%). Screening
      has identified CRC in 472 patients (5.5% of colonoscopied, 3.8% of FOBT-positive,
      and 0.26% of all screened individuals). This is also in the expected range
      according to EU Guidelines. Polyps were found and removed in 3329 (39% of
      colonoscopied) patients. The largest number of polyps were found in the left half
      of the colon: 64% (19%, 37% and 8% in the rectum, sigma, and descendens,
      respectively). The other 36% were detected in the proximal part (17% in the
      transverse colon and 19% in ceco-ascending colon). Small polyps in the rectum (5
      10 mm in diameter), sigmoid and descending colon were histologically found to be
      tubular adenomas in 60% of cases, with a low degree of dysplasia, and 40% were
      classified as hyperplastic. Polyps of this size in the transverse or ceco
      ascending colon in almost 20% had a histologically villous component, but still
      had a low degree of dysplasia. Polyps sized 10-20 mm in diameter were in 43%
      cases tubulovillous, and among them, 32% had areas with a high degree of
      dysplasia, especially those polyps in the ceco-ascending or transverse part. The
      characteristics of the Croatian CRC Screening National Program in the first 3
      years were as follows: relatively low percentage of returned FOBT, higher number
      of FOBT-positive persons but still in the range for population-based programs,
      and higher number of pathologic findings (polyps and cancers). CONCLUSION: These
      results suggest a need for intervention strategies that include organizational
      changes and educational activities to improve awareness of CRC screening
      usefulness and increase participation rates.

PMID- 22969193
TI  - Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps.
AB  - AIM: To elucidate the colonoscopic features of serrated lesions of the colorectum
      using magnifying colonoscopy. METHODS: Broad division of serrated lesions of the
      colorectum into hyperplastic polyps (HPs), traditional serrated adenomas (TSAs),
      and sessile serrated adenomas/polyps (SSA/Ps) has been proposed on the basis of
      recent molecular biological studies. However, few reports have examined the
      colonoscopic features of these divisions, including magnified colonoscopic
      findings. This study examined 118 lesions excised in our hospital as suspected
      serrated lesions after magnified observation between January 2008 and September
      2011. Patient characteristics (sex, age), conventional colonoscopic findings
      (location, size, morphology, color, mucin) and magnified colonoscopic findings
      (pit pattern diagnosis) were interpreted by five colonoscopists with experience
      in over 1000 colonoscopies, and were compared with histopathological diagnoses.
      The pit patterns were categorized according to Kudo's classification, but a more
      detailed investigation was also performed using the subclassification [type II
      Open (type II-O), type II-Long (type II-L), or type IV-Serrated (type IV-S)]
      proposed by Kimura T and Yamano H. RESULTS: Lesions comprised 23 HPs (23/118:
      19.5%), 39 TSAs (39/118: 33.1%: with cancer in one case), 50 SSA/Ps (50/118:
      42.4%: complicated with cancer in three cases), and six others (6/118: 5.1%). We
      excluded six others, including three regular adenomas, one hamartoma, one
      inflammatory polyp, and one juvenile polyp for further analysis. Conventional
      colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs
      and HPs (SSA/P vs HP, 13.62 +/- 8.62 mm vs 7.74 +/- 3.24 mm, P < 0.001; SSA/Ps vs
      TSA, 13.62 +/- 8.62 mm vs 9.89 +/- 5.73 mm, P < 0.01); common in the right side
      of the colon [HPs, 30.4% (7/23): TSAs, 20.5% (8/39): SSA/P, 84.0% (42/50), P <
      0.001]; flat-elevated lesion [HPs, 30.4% (7/23): TSAs, 5.1% (2/39): SSA/Ps, 90.0%
      (45/50), P < 0.001]; normal-colored or pale imucosa [HPs, 34.8% (8/23): TSAs,
      10.3% (4/39): SSA/Ps, 80% (40/50), P < 0.001]; and with large amounts of mucin
      [HPs, 21.7% (5/23): TSAs, 17.9% (7/39): SSA/Ps, 72.0% (36/50), P < 0.001]. In
      magnified colonoscopic findings, 17 lesions showed either type II pit pattern
      alone or partial type II pit pattern as the basic architecture, with 14 HPs
      (14/17, 70.0%) and 3 SSA/Ps. Magnified colonoscopy showed the type II-O pit
      pattern as characteristic of SSA/Ps [sensitivity 83.7% (41/49), specificity 85.7%
      (54/63)]. Cancer was also present in three lesions, in all of which a type VI pit
      pattern was also present within the same lesion. There were four HPs and four
      TSAs each. The type IV-S pit pattern was characteristic of TSAs [sensitivity
      96.7% (30/31), specificity 89.9% (72/81)]. Cancer was present in one lesion, in
      which a type VI pit pattern was also present within the same lesion. In our
      study, serrated lesions of the colorectum also possessed the features described
      in previous reports of conventional colonoscopic findings. The pit pattern
      diagnosis using magnifying colonoscopy, particularly magnified colonoscopic
      findings using subclassifications of surface architecture, reflected the
      pathological characteristics of SSA/Ps and TSAs, and will be useful for
      colonoscopic diagnosis. CONCLUSION: We suggest that this system could be a good
      diagnostic tool for SSA/Ps using magnifying colonoscopy.

PMID- 22969194
TI  - Circular smooth muscle contributes to esophageal shortening during peristalsis.
AB  - AIM: To study the angle between the circular smooth muscle (CSM) and longitudinal
      smooth muscle (LSM) fibers in the distal esophagus. METHODS: In order to identify
      possible mechanisms for greater shortening in the distal compared to proximal
      esophagus during peristalsis, the angles between the LSM and CSM layers were
      measured in 9 cadavers. The outer longitudinal layer of the muscularis propria
      was exposed after stripping the outer serosa. The inner circular layer of the
      muscularis propria was then revealed after dissection of the esophageal mucosa
      and the underlying muscularis mucosa. Photographs of each specimen were taken
      with half of the open esophagus folded back showing both the outer longitudinal
      and inner circular muscle layers. Angles were measured every one cm for 10 cm
      proximal to the squamocolumnar junction (SCJ) by two independent investigators.
      Two human esophagi were obtained from organ transplant donors and the angles
      between the circular and longitudinal smooth muscle layers were measured using
      micro-computed tomography (micro CT) and Image J software. RESULTS: All data are
      presented as mean +/- SE. The CSM to LSM angle at the SCJ and 1 cm proximal to
      SCJ on the autopsy specimens was 69.3 +/- 4.62 degrees vs 74.9 +/- 3.09 degrees,
      P = 0.32. The CSM to LSM angle at SCJ were statistically significantly lower than
      at 2, 3, 4 and 5 cm proximal to the SCJ, 69.3 +/- 4.62 degrees vs 82.58 +/- 1.34
      degrees, 84.04 +/- 1.64 degrees, 84.87 +/- 1.04 degrees and 83.72 +/- 1.42
      degrees, P = 0.013, P = 0.008, P = 0.004, P = 0.009 respectively. The CSM to LSM
      angle at SCJ was also statistically significantly lower than the angles at 6, 7
      and 8 cm proximal to the SCJ, 69.3 +/- 4.62 degrees vs 80.18 +/- 2.09 degrees,
      81.81 +/- 1.75 degrees and 80.96 +/- 2.04 degrees, P = 0.05, P = 0.02, P = 0.03
      respectively. The CSM to LSM angle at 1 cm proximal to SCJ was statistically
      significantly lower than at 3, 4 and 5 cm proximal to the SCJ, 74.94 +/- 3.09
      degrees vs 84.04 +/- 1.64 degrees, 84.87 +/- 1.04 degrees and 83.72 +/- 1.42
      degrees, P = 0.019, P = 0.008, P = 0.02 respectively. At 10 cm above SCJ the
      angle was 80.06 +/- 2.13 degrees which is close to being perpendicular but less
      than 90 degrees. The CSM to LSM angles measured on virtual dissection of the
      esophagus and the stomach on micro CT at the SCJ and 1 cm proximal to the SCJ
      were 48.39 +/- 0.72 degrees and 50.81 +/- 1.59 degrees. Rather than the angle of
      the CSM and LSM being perpendicular in the esophagus we found an acute angulation
      between these two muscle groups throughout the lower 10 cm of the esophagus.
      CONCLUSION: The oblique angulation of the CSM may contribute to the significantly
      greater shortening of distal esophagus when compared to the mid and proximal
      esophagus during peristalsis.

PMID- 22969196
TI  - Temporal trends in the relative prevalence of dysphagia etiologies from 1999
      2009.
AB  - AIM: To examine the relative prevalence and temporal variation of dysphagia
      etiologies in patients undergoing upper endoscopy (EGD) over the past decade.
      METHODS: EGDs with the indication of dysphagia at an urban, university medical
      center in 1999, 2004 and 2009 were retrospectively identified from the electronic
      medical record. The entire patient chart, including EGD, pathology, manometry,
      radiographic and clinician reports, was reviewed for demographic and clinical
      data and to determine the etiology of dysphagia. The number of EGDs in which an
      esophageal biopsy was performed was also noted. Gastroesophageal reflux disease
      (GERD) as a cause of dysphagia independent of peptic stricture was defined by
      symptoms with erosive esophagitis or symptom response to proton pump inhibition
      (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate
      clinical history and histological criteria of >= 15 eosinophils per high powered
      field. PPI-responsive esophageal eosinophilia was not routinely reported prior to
      2008. Statistical analysis was performed using one-way analysis of variance to
      analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was
      performed following a significant main effect. RESULTS: A total of 1371 cases
      (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504
      and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004
      compared to 2009 (mean +/- SD, 54.0 +/- 15.7 years vs 52.3 +/- 16.8 years, P =
      0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P =
      0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable
      causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases.
      There were no significant differences in the relative prevalence of achalasia or
      other motility disorders, peptic stricture, Schatzki's ring, esophageal cancer or
      unspecified diagnoses over the 10-year time period. There was, however, a
      decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and
      increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and
      oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc
      analyses determined that the increase in relative prevalence of EoE was
      significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P <
      0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand,
      the decrease in relative prevalence of GERD was significant between 1999 and 2009
      and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009
      (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a
      biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well
      as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did
      increase over the 10-year time period, the percentage of EGDs for the indication
      of dysphagia remained stable making increasing upper endoscopy an unlikely reason
      for the observed increased prevalence of EoE. CONCLUSION: EoE has emerged as a
      dominant cause of dysphagia in adults. Whether this was due to a rise in disease
      incidence or increased recognition is unclear.

PMID- 22969195
TI  - Screening Helicobacter pylori genes induced during infection of mouse stomachs.
AB  - AIM: To investigate the effect of in vivo environment on gene expression in
      Helicobacter pylori (H. pylori) as it relates to its survival in the host.
      METHODS: In vivo expression technology (IVET) systems are used to identify
      microbial virulence genes. We modified the IVET-transcriptional fusion vector,
      pIVET8, which uses antibiotic resistance as the basis for selection of candidate
      genes in host tissues to develop two unique IVET-promoter-screening vectors,
      pIVET11 and pIVET12. Our novel IVET systems were developed by the fusion of
      random Sau3A DNA fragments of H. pylori and a tandem-reporter system of
      chloramphenicol acetyltransferase and beta-galactosidase. Additionally, each
      vector contains a kanamycin resistance gene. We used a mouse macrophage cell
      line, RAW 264.7 and mice, as selective media to identify specific genes that H.
      pylori expresses in vivo. Gene expression studies were conducted by infecting RAW
      264.7 cells with H. pylori. This was followed by real time polymerase chain
      reaction (PCR) analysis to determine the relative expression levels of in vivo
      induced genes. RESULTS: In this study, we have identified 31 in vivo induced
      (ivi) genes in the initial screens. These 31 genes belong to several functional
      gene families, including several well-known virulence factors that are expressed
      by the bacterium in infected mouse stomachs. Virulence factors, vacA and cagA,
      were found in this screen and are known to play important roles in H. pylori
      infection, colonization and pathogenesis. Their detection validates the efficacy
      of these screening systems. Some of the identified ivi genes have already been
      implicated to play an important role in the pathogenesis of H. pylori and other
      bacterial pathogens such as Escherichia coli and Vibrio cholerae. Transcription
      profiles of all ivi genes were confirmed by real time PCR analysis of H. pylori
      RNA isolated from H. pylori infected RAW 264.7 macrophages. We compared the
      expression profile of H. pylori and RAW 264.7 coculture with that of H. pylori
      only. Some genes such as cagA, vacA, lpxC, murI, tlpC, trxB, sodB, tnpB, pgi,
      rbfA and infB showed a 2-20 fold upregulation. Statistically significant
      upregulation was obtained for all the above mentioned genes (P < 0.05). tlpC,
      cagA, vacA, sodB, rbfA, infB, tnpB, lpxC and murI were also significantly
      upregulated (P < 0.01). These data suggest a strong correlation between results
      obtained in vitro in the macrophage cell line and in the intact animal.
      CONCLUSION: The positive identification of these genes demonstrates that our IVET
      systems are powerful tools for studying H. pylori gene expression in the host
      environment.

PMID- 22969197
TI  - National trends in resection of the distal pancreas.
AB  - AIM: To investigate national trends in distal pancreatectomy (DP) through query
      of three national patient care databases. METHODS: From the Nationwide Inpatient
      Sample (NIS, 2003-2009), the National Surgical Quality Improvement Project
      (NSQIP, 2005-2010), and the Surveillance Epidemiology and End Results (SEER, 2003
      2009) databases using appropriate diagnostic and procedural codes we identified
      all patients with a diagnosis of a benign or malignant lesion of the body and/or
      tail of the pancreas that had undergone a partial or distal pancreatectomy.
      Utilization of laparoscopy was defined in NIS by the International Classification
      of Diseases, Ninth Revision correspondent procedure code; and in NSQIP by the
      exploratory laparoscopy or unlisted procedure current procedural terminology
      codes. In SEER, patients were identified by the International Classification of
      Diseases for Oncology, Third Edition diagnosis codes and the SEER Program Code
      Manual, third edition procedure codes. We analyzed the databases with respect to
      trends of inpatient outcome metrics, oncologic outcomes, and hospital volumes in
      patients with lesions of the neck and body of the pancreas that underwent
      operative resection. RESULTS: NIS, NSQIP and SEER identified 4242, 2681 and
      11,082 DP resections, respectively. Overall, laparoscopy was utilized in 15%
      (NIS) and 27% (NSQIP). No significant increase was seen over the course of the
      study. Resection was performed for malignancy in 59% (NIS) and 66% (NSQIP).
      Neither patient Body mass index nor comorbidities were associated with operative
      approach (P = 0.95 and P = 0.96, respectively). Mortality (3% vs 2%, P = 0.05)
      and reoperation (4% vs 4%, P = 1.0) was not different between laparoscopy and
      open groups. Overall complications (10% vs 15%, P < 0.001), hospital costs
      [44,741 dollars, interquartile range (IQR) 28 347-74 114 dollars vs 49 792
      dollars, IQR 13 299-73 463, P = 0.02] and hospital length of stay (7 d, IQR 4-11
      d vs 7 d, IQR 6-10, P < 0.001) were less when laparoscopy was utilized. One and
      two year survival after resection for malignancy were unchanged over the course
      of the study (ductal adenocarinoma 1-year 63.6% and 2-year 35.1%, P = 0.53;
      intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year
      84%, P = 0.25). The majority of resections were performed in teaching hospitals
      (77% NIS and 85% NSQIP), but minimally invasive surgery (MIS) was not more likely
      to be used in teaching hospitals (15% vs 14%, P = 0.26). Hospitals in the top
      decile for volume were more likely to be teaching hospitals than lower volume
      deciles (88% vs 43%, P < 0.001), but were no more likely to utilize MIS at
      resection. Complication rate in teaching and the top decile hospitals was not
      significantly decreased when compared to non-teaching (15% vs 14%, P = 0.72) and
      lower volume hospitals (14% vs 15%, P = 0.99). No difference was seen in the
      median number of lymph nodes and lymph node ratio in N1 disease when compared by
      year (P = 0.17 and P = 0.96, respectively). CONCLUSION: There appears to be an
      overall underutilization of laparoscopy for DP. Centralization does not appear to
      be occurring. Survival and lymph node harvest have not changed.

PMID- 22969198
TI  - Chronic methadone use, poor bowel visualization and failed colonoscopy: a
      preliminary study.
AB  - AIM: To examine effects of chronic methadone usage on bowel visualization,
      preparation, and repeat colonoscopy. METHODS: In-patient colonoscopy reports from
      October, 2004 to May, 2009 for methadone dependent (MD) patients were
      retrospectively evaluated and compared to matched opioid naive controls (C).
      Strict criteria were applied to exclude patients with risk factors known to cause
      constipation or gastric dysmotility. Colonoscopy reports of all eligible patients
      were analyzed for degree of bowel visualization, assessment of bowel preparation
      (good, fair, or poor), and whether a repeat colonoscopy was required. Bowel
      visualization was scored on a 4 point scale based on multiple prior studies:
      excellent = 1, good = 2, fair = 3, or poor = 4. Analysis of variance (ANOVA) and
      Pearson chi(2) test were used for data analyses. Subgroup analysis included
      correlation between methadone dose and colonoscopy outcomes. All variables
      significantly differing between MD and C groups were included in both univariate
      and multivariate logistic regression analyses. P values were two sided, and <
      0.05 were considered statistically significant. RESULTS: After applying
      exclusionary criteria, a total of 178 MD patients and 115 C patients underwent a
      colonoscopy during the designated study period. A total of 67 colonoscopy reports
      for MD patients and 72 for C were included for data analysis. Age and gender
      matched controls were randomly selected from this population to serve as controls
      in a numerically comparable group. The average age for MD patients was 52.2 +/-
      9.2 years (range: 32-72 years) years compared to 54.6 +/- 15.5 years (range: 20
      81 years) for C (P = 0.27). Sixty nine percent of patients in MD and 65% in C
      group were males (P = 0.67). When evaluating colonoscopy reports for bowel
      visualization, MD patients had significantly greater percentage of solid stool
      (i.e., poor visualization) compared to C (40.3% vs 6.9%, P < 0.001). Poor bowel
      preparation (35.8% vs 9.7%, P < 0.001) and need for repeat colonoscopy (32.8% vs
      12.5%, P = 0.004) were significantly higher in MD group compared to C,
      respectively. Under univariate analysis, factors significantly associated with MD
      group were presence of fecal particulate [odds ratio (OR), 3.89, 95% CI: 1.33
      11.36, P = 0.01] and solid stool (OR, 13.5, 95% CI: 4.21-43.31, P < 0.001). Fair
      (OR, 3.82, 95% CI: 1.63-8.96, P = 0.002) and poor (OR, 8.10, 95% CI: 3.05-21.56,
      P < 0.001) assessment of bowel preparation were more likely to be associated with
      MD patients. Requirement for repeat colonoscopy was also significant higher in MD
      group (OR, 3.42, 95% CI: 1.44-8.13, P = 0.01). In the multivariate analyses, the
      only variable independently associated with MD group was presence of solid stool
      (OR, 7.77, 95% CI: 1.66-36.47, P = 0.01). Subgroup analysis demonstrated a
      general trend towards poorer bowel visualization with higher methadone dosage.
      ANOVA analysis demonstrated that mean methadone dose associated with presence of
      solid stool (poor visualization) was significantly higher compared to mean dosage
      for clean colon (excellent visualization, P = 0.02) or for those with liquid
      stool only (good visualization, P = 0.01). CONCLUSION: Methadone dependence is a
      risk factor for poor bowel visualization and leads to more repeat colonoscopies.
      More aggressive bowel preparation may be needed in MD patients.

PMID- 22969199
TI  - Predictive value of symptoms and demographics in diagnosing malignancy or peptic
      stricture.
AB  - AIM: To determine which features of history and demographics predict a diagnosis
      of malignancy or peptic stricture in patients presenting with dysphagia. METHODS:
      A prospective case-control study of 2000 consecutive referrals (1031 female, age
      range: 17-103 years) to a rapid access service for dysphagia, based in a teaching
      hospital within the United Kingdom, over 7 years. The service consists of a nurse
      led telephone triage followed by investigation (barium swallow or gastroscopy),
      if appropriate, within 2 wk. Logistic regression analysis of demographic and
      clinical variables was performed. This includes age, sex, duration of dysphagia,
      whether to liquids or solids, and whether there are associated features (reflux,
      odynophagia, weight loss, regurgitation). We determined odds ratio (OR) for these
      variables for the diagnoses of malignancy and peptic stricture. We determined the
      value of the Edinburgh Dysphagia Score (EDS) in predicting cancer in our cohort.
      Multivariate logistic regression was performed and P < 0.05 considered
      significant. The local ethics committee confirmed ethics approval was not
      required (audit). RESULTS: The commonest diagnosis is gastro-esophageal reflux
      disease (41.3%). Malignancy (11.0%) and peptic stricture (10.0%) were also
      relatively common. Malignancies were diagnosed by histology (97%) or on
      radiological criteria, either sequential barium swallows showing progression of
      disease or unequivocal evidence of malignancy on computed tomography. The
      majority of malignancies were esophago-gastric in origin but ear, nose and throat
      tumors, pancreatic cancer and extrinsic compression from lung or mediastinal
      metastatic cancer were also found. Malignancy was statistically more frequent in
      older patients (aged >73 years, OR 1.1-3.3, age < 60 years 6.5%, 60-73 years
      11.2%, > 73 years 11.8%, P < 0.05), males (OR 2.2-4.8, males 14.5%, females 5.6%,
      P < 0.0005), short duration of dysphagia (<= 8 wk, OR 4.5-20.7, 16.6%, 8-26 wk
      14.5%, > 26 wk 2.5%, P < 0.0005), progressive symptoms (OR 1.3-2.6: progressive
      14.8%, intermittent 9.3%, P < 0.001), with weight loss of >= 2 kg (OR 2.5-5.1,
      weight loss 22.1%, without weight loss 6.4%, P < 0.0005) and without reflux (OR
      1.2-2.5, reflux 7.2%, no reflux 15.5%, P < 0.0005). The likelihood of malignancy
      was greater in those who described true dysphagia (food or drink sticking within
      5 s of swallowing than those who did not (15.1% vs 5.2% respectively, P < 0.001).
      The sensitivity, specificity, positive predictive value and negative predictive
      value of the EDS were 98.4%, 9.3%, 11.8% and 98.0% respectively. Three patients
      with an EDS of 3 (high risk EDS >= 3.5) had malignancy. Unlike the original
      validation cohort, there was no difference in likelihood of malignancy based on
      level of dysphagia (pharyngeal level dysphagia 11.9% vs mid sternal or lower
      sternal dysphagia 12.4%). Peptic stricture was statistically more frequent in
      those with longer duration of symptoms (> 6 mo, OR 1.2-2.9, <= 8 wk 9.8%, 8-26 wk
      10.6%, > 26 wk 15.7%, P < 0.05) and over 60 s (OR 1.2-3.0, age < 60 years 6.2%,
      60-73 years 10.2%, > 73 years 10.6%, P < 0.05). CONCLUSION: Malignancy and peptic
      stricture are frequent findings in those referred with dysphagia. The predictive
      value for associated features could help determine need for fast track
      investigation whilst reducing service pressures.

PMID- 22969200
TI  - How many cases of laryngopharyngeal reflux suspected by laryngoscopy are
      gastroesophageal reflux disease-related?
AB  - AIM: To investigate the prevalence of gastroesophageal reflux disease (GERD) in
      patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR).
      METHODS: Between May 2011 and October 2011, 41 consecutive patients with
      laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were
      empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the
      therapeutic outcome was assessed through validated questionnaires (GERD impact
      scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose
      and throat specialists using the reflux finding score (RFS) and reflux symptom
      index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper
      endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal
      impedance and pH (MII-pH) esophageal monitoring. A positive correlation between
      LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD),
      pathological acid exposure time (AET) in the absence of esophageal erosions
      (NERD), and a positive correlation between symptoms and refluxes (hypersensitive
      esophagus, HE). RESULTS: The male/female ratio was 0.52 (14/27), the mean age +/-
      SD was 51.5 +/- 12.7 years, and the mean body mass index was 25.7 +/- 3.4
      kg/m(2). All subjects reported one or more LPS. Twenty-five out of 41 patients
      also had typical GERD symptoms (heartburn and/or regurgitation). The most
      frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41),
      linear indentation in the medial edge of the vocal fold (31/41), vocal fold
      nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed
      that 10/41 patients reported symptom relief with PPI therapy (P < 0.05);
      conversely, 23/41 did not report any clinical improvement. At the same time, the
      VAS analysis showed a significant reduction in typical GERD symptoms after PPI
      therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand,
      such result was not recorded for LPS. Esophagitis was detected in 2/41 patients,
      and ineffective esophageal motility was found in 3/41 patients. The MII-pH
      analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41
      patients had a normal AET and a positive association between symptoms and
      refluxes (HE), and 25/41 patients had a normal AET and a negative association
      between symptoms and refluxes (no GERD patients). It is noteworthy that HE
      patients had a positive association with typical GERD-related symptoms. Gas
      refluxes were found more frequently in patients with globus (29.7 +/- 3.6) and
      hoarseness (21.5 +/- 7.4) than in patients with heartburn or regurgitation (7.8
      +/- 6.2). Gas refluxes were positively associated with extra-esophageal symptoms
      (P < 0.05). Overall, no differences were found among the three groups of patients
      in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in
      patients with ERD/NERD only. The differences observed by means of MII-pH analysis
      among the three subgroups of patients (ERD/NERD, HE, no GERD) were not
      demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was
      found to have a significant association with the RFS (P = 0.028 and P = 0.026,
      nominal and numerical correlation, respectively). CONCLUSION: MII-pH analysis
      confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of
      LPR, most likely because of the low specificity of the laryngoscopic findings.

PMID- 22969201
TI  - Alginate controls heartburn in patients with erosive and nonerosive reflux
      disease.
AB  - AIM: To evaluate the effect of a novel alginate-based compound, Faringel, in
      modifying reflux characteristics and controlling symptoms. METHODS: In this
      prospective, open-label study, 40 patients reporting heartburn and regurgitation
      with proven reflux disease (i.e., positive impedance-pH test/evidence of erosive
      esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a
      refluxogenic meal. They were studied for 1 h under basal conditions and 1 h after
      taking 10 mL Faringel. In both sessions, measurements were obtained in right
      lateral and supine decubitus positions. Patients also completed a validated
      questionnaire consisting of a 2-item 5-point (0-4) Likert scale and a 10-cm
      visual analogue scale (VAS) in order to evaluate the efficacy of Faringel in
      symptom relief. Tolerability of the treatment was assessed using a 6-point Likert
      scale ranging from very good (1) to very poor (6). RESULTS: Faringel decreased
      significantly (P < 0.001), in both the right lateral and supine decubitus
      positions, esophageal acid exposure time [median 10 (25th-75th percentil 6-16) vs
      5.8 (4-10) and 16 (11-19) vs 7.5 (5-11), respectively] and acid refluxes [5 (3-8)
      vs 1 (1-1) and 6 (4-8) vs 2 (1-2), respectively], but increased significantly (P
      < 0.01) the number of nonacid reflux events compared with baseline [2 (1-3) vs 3
      (2-5) and 3 (2-4) vs 6 (3-8), respectively]. Percentage of proximal migration
      decreased in both decubitus positions (60% vs 32% and 64% vs 35%, respectively; P
      < 0.001). Faringel was significantly effective in controlling heartburn, based on
      both the Likert scale [3.1 (range 1-4) vs 0.9 (0-2); P < 0.001] and VAS score
      [7.1 (3-9.8) vs 2 (0.1-4.8); P < 0.001], but it had less success against
      regurgitation, based on both the Likert scale [2.6 (1-4) vs 2.2 (1-4); P = not
      significant (NS)] and VAS score [5.6 (2-9.6) vs 3.9 (1-8.8); P = NS]. Overall,
      the tolerability of Faringel was very good 5 (2-6), with only two patients
      reporting modest adverse events (i.e., nausea and bloating). CONCLUSION: Our
      findings demonstrate that Faringel is well-tolerated and effective in reducing
      heartburn by modifying esophageal acid exposure time, number of acid refluxes and
      their proximal migration.

PMID- 22969202
TI  - Prevalence of functional dyspepsia and its subgroups in patients with eating
      disorders.
AB  - AIM: To study the prevalence of functional dyspepsia (FD) (Rome III criteria)
      across eating disorders (ED), obese patients, constitutional thinner and healthy
      volunteers. METHODS: Twenty patients affected by anorexia nervosa, 6 affected by
      bulimia nervosa, 10 affected by ED not otherwise specified according to
      diagnostic and statistical manual of mental disorders, 4th edition, nine
      constitutional thinner subjects and, thirty-two obese patients were recruited
      from an outpatients clinic devoted to eating behavior disorders. Twenty-two
      healthy volunteers matched for age and gender were enrolled as healthy controls.
      All participants underwent a careful clinical examination. Demographic and
      anthropometric characteristics were obtained from a structured questionnaires.
      The presence of FD and, its subgroups, epigastric pain syndrome and postprandial
      distress syndrome (PDS) were diagnosed according to Rome III criteria. The
      intensity-frequency score of broader dyspeptic symptoms such as early satiety,
      epigastric fullness, epigastric pain, epigastric burning, epigastric pressure,
      belching, nausea and vomiting were studied by a standardized questionnaire (0-6).
      Analysis of variance and post-hoc Sheffe tests were used for comparisons.
      RESULTS: 90% of patients affected by anorexia nervosa, 83.3% of patients affected
      by bulimia nervosa, 90% of patients affected by ED not otherwise specified, 55.6%
      of constitutionally thin subjects and 18.2% healthy volunteers met the
      Postprandial Distress Syndrome Criteria (chi(2), P < 0.001). Only one bulimic
      patient met the epigastric pain syndrome diagnosis. Postprandial fullness
      intensity-frequency score was significantly higher in anorexia nervosa, bulimia
      nervosa and ED not otherwise specified groups compared to the score calculated in
      the constitutional thinner group (4.15 +/- 2.08 vs 1.44 +/- 2.35, P = 0.003; 5.00
      +/- 2.45 vs 1.44 +/- 2.35, P = 0.003; 4.10 +/- 2.23 vs 1.44 +/- 2.35, P = 0.002,
      respectively), the obese group (4.15 +/- 2.08 vs 0.00 +/- 0.00, P < 0.001; 5.00
      +/- 2.45 vs 0.00 +/- 0.00, P < 0.001; 4.10 +/- 2.23 vs 0.00 +/- 0.00, P < 0.001,
      respectively) and healthy volunteers (4.15 +/- 2.08 vs 0.36 +/- 0.79, P < 0.001;
      5.00 +/- 2.45 vs 0.36 +/- 0.79, P < 0.001; 4.10 +/- 2.23 vs 0.36 +/- 0.79, P <
      0.001, respectively). Early satiety intensity-frequency score was prominent in
      anorectic patients compared to bulimic patients (3.85 +/- 2.23 vs 1.17 +/- 1.83,
      P = 0.015), obese patients (3.85 +/- 2.23 vs 0.00 +/- 0.00, P < 0.001) and
      healthy volunteers (3.85 +/- 2.23 vs 0.05 +/- 0.21, P < 0.001). Nausea and
      epigastric pressure were increased in bulimic and ED not otherwise specified
      patients. Specifically, nausea intensity-frequency-score was significantly higher
      in bulimia nervosa and ED not otherwise specified patients compared to anorectic
      patients (3.17 +/- 2.56 vs 0.89 +/- 1.66, P = 0.04; 2.70 +/- 2.91 vs 0.89 +/-
      1.66, P = 0.05, respectively), constitutional thinner subjects (3.17 +/- 2.56 vs
      0.00 +/- 0.00, P = 0.004; 2.70 +/- 2.91 vs 0.00 +/- 0.00, P = 0.005,
      respectively), obese patients (3.17 +/- 2.56 vs 0.00 +/- 0.00, P < 0.001; 3.17 +/
      2.56 vs 0.00 +/- 0.00, P < 0.001 respectively) and, healthy volunteers (3.17 +/-
      2.56 vs 0.17 +/- 0.71, P = 0.002; 3.17 +/- 2.56 vs 0.17 +/- 0.71, P = 0.001,
      respectively). Epigastric pressure intensity-frequency score was significantly
      higher in bulimic and ED not otherwise specified patients compared to
      constitutional thin subjects (4.67 +/- 2.42 vs 1.22 +/- 1.72, P = 0.03; 4.20 +/-
      2.21 vs 1.22 +/- 1.72, P = 0.03, respectively), obese patients (4.67 +/- 2.42 vs
      0.75 +/- 1.32, P = 0.001; 4.20 +/- 2.21 vs 0.75 +/- 1.32, P < 0.001,
      respectively) and, healthy volunteers (4.67 +/- 2.42 vs 0.67 +/- 1.46, P = 0.001;
      4.20 +/- 2.21 vs 0.67 +/- 1.46, P = 0.001, respectively). Vomiting was referred
      in 100% of bulimia nervosa patients, in 20% of ED not otherwise specified
      patients, in 15% of anorexia nervosa patients, in 22% of constitutional thinner
      subjects, and, in 5.6% healthy volunteers (chi(2), P < 0.001). CONCLUSION: PDS is
      common in eating disorders. Is it mandatory in outpatient gastroenterological
      clinics to investigate eating disorders in patients with PDS?

PMID- 22969203
TI  - Quadruple therapy with moxifloxacin and bismuth for first-line treatment of
      Helicobacter pylori.
AB  - AIM: To compare triple therapy vs quadruple therapy for 10 d as first-line
      treatment of Helicobacter pylori (H. pylori) infection. METHODS: Consecutive H.
      pylori positive patients never treated in the past for this infection were
      randomly treated with triple therapy of pantoprazole (PAN) 20 mg bid, amoxicillin
      (AMO) 1 g bid and moxifloxacin (MOX) 400 mg bid for 10 d (PAM) or with quadruple
      therapy of PAN 20 mg bid, AMO 1 g bid, MOX 400 mg bid and bismuth subcitrate 240
      mg bid for 10 d (PAMB). All patients were found positive at 13 C-Urea breath test
      (UBT) performed within ten days prior to the start of the study. A successful
      outcome was confirmed with an UBT performed 8 wk after the end of treatment.
      chi(2) analysis was used for statistical comparison. Per protocol (PP) and
      intention-to-treat (ITT) values were also calculated. RESULTS: Fifty-seven
      patients were enrolled in the PAM group and 50 in the PAMB group. One patient in
      each group did not return for further assessment. Eradication was higher in the
      PAMB group (negative: 46 and positive: 3) vs the PAM group (negative: 44 and
      positive: 12). The H. pylori eradication rate was statistically significantly
      higher in the PAMB group vs the PAM group, both with the PP and ITT analyses (PP:
      PAMB 93.8%, PAM 78.5%, P < 0.02; ITT: PAMB 92%, PAM 77.1 %, P <0.03). CONCLUSION:
      The addition of bismuth subcitrate can be considered a valuable adjuvant to
      triple therapy in those areas where H. pylori shows a high resistance to
      fluoroquinolones.

PMID- 22969204
TI  - Adalimumab in prevention of postoperative recurrence of Crohn's disease in high
      risk patients.
AB  - AIM: To evaluate the effectiveness of adalimumab in preventing recurrence after
      intestinal resection for Crohn's disease in high-risk patients. METHODS: A
      multicenter, prospective, observational study was conducted from June 2009 until
      June 2010. We consecutively included high-risk Crohn's disease patients who had
      undergone an ileal/ileocolonic resection. High-risk patients were defined as two
      or more criteria: smokers, penetrating pattern, one or more previous surgical
      resections or prior extensive resection. Subcutaneous adalimumab was administered
      2 wk (+/- 5 d) after surgery at a dose of 40 mg eow, with an initial induction
      dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant
      treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or
      biologic therapies), smoking status at the time of diagnosis and after the index
      operation and number of previous resections (type and reason for surgery) were
      all recorded. Biological status was assessed with C-reactive protein, erythrocyte
      sedimentation rate and fecal calprotectin. One year (+/- 3 mo) after surgery, an
      ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic
      recurrence was defined as Rutgeerts score >= i2. Morphological recurrence was
      based on magnetic resonance (MR) score >= MR1. RESULTS: Twenty-nine patients
      (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation),
      mean age 42.3 years and mean duration of the disease 13.8 years were included in
      the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab
      administration and in 37.9% was considered extensive resection. 51.7% had
      previously received infliximab. Immunomodulators were given concomitantly to
      17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29
      (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1
      year. All patients with clinical recurrence showed endoscopic and morphological
      recurrence. A high degree of concordance was found between clinical-endoscopic
      recurrence (kappa = 0.76, P < 0.001) and clinical-morphological recurrence (kappa
      = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was
      good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of
      i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r(s) = 0.825).
      During follow-up, five (17.2%) patients needed adalimumab dose intensification
      (40 mg/wk); Mean time to intensification after the introduction of adalimumab
      treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological
      change was needed due to a worsening of the disease after the dose
      intensification to 40 mg/wk. One patient suffered an adverse event. CONCLUSION:
      Adalimumab seems to be effective and safe in preventing postoperative recurrence
      in a selected group of patients who had undergone an intestinal resection for
      their CD.

PMID- 22969205
TI  - Tissue transglutaminase levels above 100 U/mL and celiac disease: a prospective
      study.
AB  - AIM: To investigate whether a tissue-transglutaminase antibody (tTGA) level >=
      100 U/mL is sufficient for the diagnosis of celiac disease (CD). METHODS:
      Children suspected of having CD were prospectively included in our study between
      March 2009 and September 2011. All patients with immune globulin A deficiency and
      all patients on a gluten-free diet were excluded from the study. Anti-endomysium
      antibodies (EMA) were detected by means of immunofluorescence using sections of
      distal monkey esophagus (EUROIMMUN, Luebeck, Germany). Serum anti-tTGA were
      measured by means of enzyme-linked immunosorbent assay using human recombinant
      tissue transglutaminase (ELiA Celikey IgA kit Phadia AB, Uppsala, Sweden). The
      histological slides were graded by a single experienced pathologist using the
      Marsh classification as modified by Oberhuber. Marsh II and III lesions were
      considered to be diagnostic for the disease. The positive predictive values
      (PPVs), negative predictive values (NPVs), sensitivity and specificity of EMA and
      tTGA along with their 95% CI (for the cut off values > 10 and >= 100 U/mL) were
      calculated using histology as the gold standard for CD. RESULTS: A total of 183
      children were included in the study. A total of 70 (38.3%) were male, while 113
      (61.7%) were female. The age range was between 1.0 and 17.6 years, and the mean
      age was 6.2 years. One hundred twenty (65.6%) patients had a small intestinal
      biopsy diagnostic for the disease; 3 patients had a Marsh II lesion, and 117
      patients had a Marsh III lesion. Of the patients without CD, only 4 patients had
      a Marsh I lesion. Of the 183 patients, 136 patients were positive for EMA, of
      whom 20 did not have CD, yielding a PPV for EMA of 85% (95% CI: 78%-90%) and a
      corresponding specificity of 68% (95% CI: 55%-79%). The NPV and specificity for
      EMA were 91% (95% CI: 79%-97%) and 97% (95% CI: 91%-99%), respectively. Increased
      levels of tTGA were found in 130 patients, although only 116 patients truly had
      histological evidence of the disease. The PPV for tTGA was 89% (95% CI: 82%-94%),
      and the corresponding specificity was 78% (95% CI: 65%-87%). The NPV and
      sensitivity were 92% (95% CI: 81%-98%) and 97% (95% CI: 91%-99%), respectively. A
      tTGA level >= 100 U/mL was found in 87 (47.5%) patients, all of whom were also
      positive for EMA. In all these 87 patients, epithelial lesions confirming CD were
      found, giving a PPV of 100% (95%CI: 95%-100%). The corresponding specificity for
      this cut-off value was also 100% (95% CI: 93%-100%). Within this group, a total
      of 83 patients had symptoms, at least gastrointestinal and/or growth retardation.
      Three patients were asymptomatic but were screened because they belonged to a
      group at risk for CD (diabetes mellitus type 1 or positive family history). The
      fourth patient who lacked CD-symptoms was detected by coincidence during an
      endoscopy performed for gastro-intestinal bleeding. CONCLUSION: This study
      confirms based on prospective data that a small intestinal biopsy is not
      necessary for the diagnosis of CD in symptomatic patients with tTGA >= 100 U/mL.

PMID- 22969206
TI  - Comparison of bacterial quantities in left and right colon biopsies and faeces.
AB  - AIM: To compare quantities of predominant and pathogenic bacteria in mucosal and
      faecal samples. METHODS: Twenty patients undergoing diagnostic colonoscopy with
      endoscopically and histologically normal mucosa were recruited to the study, 14
      subjects of which also supplied faecal (F) samples between 15 d to 105 d post
      colonoscopy. Mucosal biopsies were taken from each subject from the midportion of
      the ascending colon (right side samples, RM) and the sigmoid (left side samples,
      LM). Predominant intestinal and mucosal bacteria including clostridial 16S rRNA
      gene clusters IV and XIVab, Bacteroidetes, Enterobacteriaceae, Bifidobacterium
      spp., Akkermansia muciniphila (A. muciniphila), Veillonella spp., Collinsella
      spp., Faecalibacterium prausnitzii (F. prausnitzii) and putative pathogens such
      as Escherichia coli (E. coli), Clostridium difficile (C. difficile), Helicobacter
      pylori (H. pylori) and Staphylococcus aureus (S. aureus) were analysed by
      quantitative polymerase chain reaction (qPCR). Host DNA was quantified from the
      mucosal samples with human glyceraldehyde 3-phosphate dehydrogenase gene
      targeting qPCR. Paired t tests and the Pearson correlation were applied for
      statistical analysis. RESULTS: The most prominent bacterial groups were
      clostridial groups IV and XIVa+b and Bacteroidetes and bacterial species F.
      prausnitzii in both sample types. H. pylori and S. aureus were not detected and
      C. difficile was detected in only one mucosal sample and three faecal samples. E.
      coli was detected in less than half of the mucosal samples at both sites, but was
      present in all faecal samples. All detected bacteria, except Enterobacteriaceae,
      were present at higher levels in the faeces than in the mucosa, but the different
      locations in the colon presented comparable quantities (RM, LM and F followed by
      P(1) for RM vs F, P(2) for LM vs F and P(3) for RM vs LM: 4.17 +/- 0.60
      log(10)/g, 4.16 +/- 0.56 log(10)/g, 5.88 +/- 1.92 log(10)/g, P(1) = 0.011, P(2) =
      0.0069, P(3) = 0.9778 for A. muciniphila; 6.25 +/- 1.3 log(10)/g, 6.09 +/- 0.81
      log(10)/g, 8.84 +/- 1.38 log(10)/g, P(1) < 0.0001, P(2) = 0.0002, P(3) = 0.6893
      for Bacteroidetes; 5.27 +/- 1.68 log(10)/g, 5.38 +/- 2.06 log(10)/g, 8.20 +/-
      1.14 log(10)/g, P(1) < 0.0001, P(2) <= 0.0001, P(3) = 0.7535 for Bifidobacterium
      spp.; 6.44 +/- 1.15 log(10)/g, 6.07 +/-1.45 log(10)/g, 9.74 +/-1.13 log(10)/g,
      P(1) < 0.0001, P(2) <= 0.0001, P(3) = 0.637 for Clostridium cluster IV; 6.65 +/-
      1.23 log(10)/g, 6.57 +/- 1.52 log(10)/g, 9.13 +/- 0.96 log(10)/g, P(1) < 0.0001,
      P(2) <= 0.0001, P(3) = 0.9317 for Clostridium cluster XIVa; 4.57 +/- 1.44
      log(10)/g, 4.63 +/- 1.34 log(10)/g, 7.05 +/- 2.48 log(10)/g, P(1) = 0.012, P(2) =
      0.0357, P(3) = 0.7973 for Collinsella spp.; 7.66 +/- 1.50 log(10)/g, 7.60 +/-
      1.05 log(10)/g, 10.02 +/- 2.02 log(10)/g, P(1) <= 0.0001, P(2) = 0.0013, P(3) =
      0.9919 for F. prausnitzsii; 6.17 +/- 1.3 log(10)/g, 5.85 +/- 0.93 log(10)/g, 7.25
      +/- 1.01 log(10)/g, P(1) = 0.0243, P(2) = 0.0319, P(3) = 0.6982 for Veillonella
      spp.; 4.68 +/- 1.21 log(10)/g, 4.71 +/- 0.83 log(10)/g, 5.70 +/- 2.00 log(10)/g,
      P(1) = 0.1927, P(2) = 0.0605, P(3) = 0.6476 for Enterobacteriaceae). The
      Bifidobacterium spp. counts correlated significantly between mucosal sites and
      mucosal and faecal samples (Pearson correlation coefficients 0.62, P = 0.040 and
      0.81, P = 0.005 between the right mucosal sample and faeces and the left mucosal
      sample and faeces, respectively). CONCLUSION: Non-invasive faecal samples do not
      reflect bacterial counts on the mucosa at the individual level, except for
      bifidobacteria often analysed in probiotic intervention studies.

PMID- 22969207
TI  - Significant decrease in prevalence of Helicobacter pylori in the Czech Republic.
AB  - AIM: To study possible decrease in prevalence of Helicobacter pylori (H. pylori)
      infection in the Czech Republic within a 10-year period. METHODS: A total of 22
      centres entered the study. The catchment areas of these centres covered cities
      and towns with more than 20,000 inhabitants, smaller towns (<= 20,000
      inhabitants) with surrounding villages and rural areas, and were spread over the
      whole country, corresponding well to the geographical distribution of the Czech
      population. A total of 1,837 subjects (aged 5-98 years) took part in the study,
      randomly selected out of 38,147 people from the general population. H. pylori
      infection was investigated by means of a (13)C-urea breath test. Breath samples
      in duplicates were analysed using isotope ratio mass spectrometry. The cut-off
      point was 3.5. Social and demographic characteristics were based on data from
      self-completed questionnaires. RESULTS: The overall prevalence of H. pylori
      infection was 23.5% (430/1826), and 4.8% (20/420) in children aged 15 or less.
      There was no statistically significant difference in prevalence between males
      (24.3%; 208/857) and females (22.9%, 222/969, P = 0.494). H. pylori infection was
      strongly associated with higher age, among subjects aged 55+ years, prevalence of
      H. pylori infection was 39.8% (252/633, P < 0.001). The highest prevalence of H.
      pylori infection was found among persons aged 55-64 years (43.9%, 97/221) and 75+
      years (37.9%, 58/153). Among study subjects aged 15+ years, prevalence of H.
      pylori infection was significantly increased in those with lowest education (odds
      risk 3.19, 95% CI 1.87-5.47). Compared to never married (14.1%), the prevalence
      of H. pylori infection was statistically significantly higher among married
      (35.4%, 246/694, P < 0.001), divorced (36.8%, 49/133, P < 0.001) and widowed
      study subjects (40.2%, 45/112, P < 0.001), both in minimally and fully adjusted
      analysis. There was no significant difference in the prevalence of H. pylori
      infection between married and widowed subjects (35.4%, 246/694 vs 40.2%, 45/112,
      P = 0.389). There was little variation in smoking prevalence across categories of
      smoking and there was no evidence of an increased risk of H. pylori infection
      among current or past smokers in our data (odds risk 1.04 with 95% CI 0.78-1.40
      for current smokers; odds ratio 0.83 with 95% CI 0.60-1.16 for former smokers).
      The current prevalence of H. pylori in 2011 was significantly lower compared to
      the prevalence reported from identical geographical areas in 2001 (23.5% vs
      41.7%, P < 0.001). CONCLUSION: The overall prevalence of H. pylori infection in
      the general population has fallen substantially in the Czech Republic over the
      past 10 years.

PMID- 22969208
TI  - Development of a quantum-dot-labelled magnetic immunoassay method for circulating
      colorectal cancer cell detection.
AB  - AIM: To detect of colorectal cancer (CRC) circulating tumour cells (CTCs) surface
      antigens, we present an assay incorporating cadmium selenide quantum dots (QDs)
      in these paper. METHODS: The principle of the assay is the immunomagnetic
      separation of CTCs from body fluids in conjunction with QDs, using specific
      antibody biomarkers: epithelial cell adhesion molecule antibody, and monoclonal
      cytokeratin 19 antibody. The detection signal was acquired from the fluorescence
      signal of QDs. For the evaluation of the performance, the method under study was
      used to isolate the human colon adenocarcinoma cell line (DLD-1) and CTCs from
      CRC patients' peripheral blood. RESULTS: The minimum detection limit of the assay
      was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a
      spectrofluorometer. Fluorescence-activated cell sorting analysis and Real Time RT
      PCR, they both have also been used to evaluate the performance of the described
      method. In conclusion, we developed a simple, sensitive, efficient and of lower
      cost (than the existing ones) method for the detection of CRC CTCs in human
      samples. We have accomplished these results by using magnetic bead isolation and
      subsequent QD fluorescence detection. CONCLUSION: The method described here can
      be easily adjusted for any other protein target of either the CTC or the host.

PMID- 22969209
TI  - Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver
      tumors.
AB  - AIM: To study the role of time-intensity curve (TIC) analysis parameters in a
      complex system of neural networks designed to classify liver tumors. METHODS: We
      prospectively included 112 patients with hepatocellular carcinoma (HCC) (n = 41),
      hypervascular (n = 20) and hypovascular (n = 12) liver metastases, hepatic
      hemangiomas (n = 16) or focal fatty changes (n = 23) who underwent contrast
      enhanced ultrasonography in the Research Center of Gastroenterology and
      Hepatology, Craiova, Romania. We recorded full length movies of all contrast
      uptake phases and post-processed them offline by selecting two areas of interest
      (one for the tumor and one for the healthy surrounding parenchyma) and
      consecutive TIC analysis. The difference in maximum intensities, the time to
      reaching them and the aspect of the late/portal phase, as quantified by the
      neural network and a ratio between median intensities of the central and
      peripheral areas were analyzed by a feed forward back propagation multi-layer
      neural network which was trained to classify data into five distinct classes,
      corresponding to each type of liver lesion. RESULTS: The neural network had
      94.45% training accuracy (95% CI: 89.31%-97.21%) and 87.12% testing accuracy (95%
      CI: 86.83%-93.17%). The automatic classification process registered 93.2%
      sensitivity, 89.7% specificity, 94.42% positive predictive value and 87.57%
      negative predictive value. The artificial neural networks (ANN) incorrectly
      classified as hemangyomas three HCC cases and two hypervascular metastases, while
      in turn misclassifying four liver hemangyomas as HCC (one case) and hypervascular
      metastases (three cases). Comparatively, human interpretation of TICs showed
      94.1% sensitivity, 90.7% specificity, 95.11% positive predictive value and 88.89%
      negative predictive value. The accuracy and specificity of the ANN diagnosis
      system was similar to that of human interpretation of the TICs (P = 0.225 and P =
      0.451, respectively). Hepatocellular carcinoma cases showed contrast uptake
      during the arterial phase followed by wash-out in the portal and first seconds of
      the late phases. For the hypovascular metastases did not show significant
      contrast uptake during the arterial phase, which resulted in negative differences
      between the maximum intensities. We registered wash-out in the late phase for
      most of the hypervascular metastases. Liver hemangiomas had contrast uptake in
      the arterial phase without agent wash-out in the portal-late phases. The focal
      fatty changes did not show any differences from surrounding liver parenchyma,
      resulting in similar TIC patterns and extracted parameters. CONCLUSION: Neural
      network analysis of contrast-enhanced ultrasonography - obtained TICs seems a
      promising field of development for future techniques, providing fast and reliable
      diagnostic aid for the clinician.

PMID- 22969210
TI  - Endoscopic ultrasound-guided choledochoduodenostomies with fully covered self
      expandable metallic stents.
AB  - AIM: To investigate the long-term outcomes of endoscopic ultrasound-guided
      choledochoduodenostomy (EUS-CDS) with a fully covered self-expandable metallic
      stent (FCSEMS). METHODS: From April 2009 to August 2010, 15 patients with distal
      malignant biliary obstructions who were candidates for alternative techniques for
      biliary decompression due to a failed endoscopic retrograde
      cholangiopancreatography (ERCP) were included. These 15 patients consisted of 8
      men and 7 women and had a median age of 61 years (range: 30-91 years). The
      underlying causes of the distal malignant biliary obstruction were pancreatic
      cancer (n = 9), ampulla of Vater cancer (n = 2), renal cell carcinoma (n = 1),
      advanced gastric cancer (n = 1), lymphoma (n = 1), and duodenal cancer (n = 1).
      RESULTS: The technical success rate of EUS-CDS with an FCSEMS was 86.7% (13/15),
      and functional success was achieved in 100% (13/13) of those cases. In two
      patients, the EUS-CDS failed because an FCSEMS with a delivery device could not
      be passed into the common bile duct. The mean duration of stent patency was 264
      d. Early adverse events developed in three patients (3/13, 23.1%), including self
      limited pneumoperitoneum in two patients and cholangitis requiring stent
      reposition in one patient. During the follow-up period (median: 186 d, range: 52
      388 d), distal stent migration occurred in four patients (4/13, 30.8%). In 3
      patients, the FCSEMS could be reinserted through the existing choledochoduodenal
      fistula tract. CONCLUSION: EUS-CDS with an FCSEMS is technically feasible and can
      lead to effective palliation of distal malignant biliary obstructions after
      failed ERCP.

PMID- 22969211
TI  - Favorable surgical treatment outcomes for chronic constipation with features of
      colonic pseudo-obstruction.
AB  - AIM: To determine long-term outcomes of surgical treatments for patients with
      constipation and features of colonic pseudo-obstruction. METHODS: Consecutive 42
      patients who underwent surgery for chronic constipation within the last 13 years
      were prospectively collected. We identified a subgroup with colonic pseudo
      obstruction (CPO) features, with dilatation of the colon proximal to the narrowed
      transitional zone, in contrast to typical slow-transit constipation (STC),
      without any dilated colonic segments. The outcomes of surgical treatments for
      chronic constipation with features of CPO were analyzed and compared with
      outcomes for STC. RESULTS: Of the 42 patients who underwent surgery for
      constipation, 33 patients had CPO with dilatation of the colon proximal to the
      narrowed transitional zone. There were 16 males and 17 females with a mean age of
      51.2 +/- 16.1 years. All had symptoms of chronic intestinal obstruction,
      including abdominal distension, pain, nausea, or vomiting, and the mean duration
      of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was
      1.5 +/- 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total
      colectomy, and one patient underwent diverting transverse colostomy. There was no
      surgery-related mortality. Postoperative histologic examination showed
      hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with
      visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC
      group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy
      (n = 3). Early postoperative complications developed in six patients with CPO;
      wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n =
      1). Defecation frequencies 3 mo after surgery improved to 4.2 +/- 3.2 times/d
      (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32
      patients; all patients had improvements in constipation symptoms, but two
      patients needed intermittent medication for management of diarrhea. All 32
      patients had distinct improvements in constipation symptoms (with a mean bowel
      frequency of 3.3 +/- 1.3 times/d), social activities, and body mass index (20.5
      kg/m(2) to 22.1 kg/m(2)) and were satisfied with the results of their surgical
      treatment. In comparison with nine patients who underwent colectomy for STC
      without colon dilatation, those in the CPO group had a lower incidence of small
      bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance
      travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up. CONCLUSION: Chronic
      constipation patients with features of CPO caused by narrowed transitional zone
      in the left colon had favorable outcomes after total colectomy.

PMID- 22969212
TI  - In vivo detection of mucosal healing-involved histiocytes by confocal laser
      endomicroscopy.
AB  - Histiocytes have a pivotal role in wound repair and intestinal epithelial
      recovery - the most important goal to sustain gut functionality. Yet, an in vivo
      description of colonic histiocytes by confocal laser endomicroscopy (CLE) is
      missing. Here, we report the case of a 45-years-old male patient who was referred
      to our clinic with weight loss and a history of two consecutive Clostridium
      difficile colitis episodes, the latter cured 3 wk before present admission. Stool
      microbiology was negative. Conventional colonoscopy showed atrophy and a light
      mucosal oedema in the distal colon. During on-going endoscopy, we performed a
      fluorescein-aided CLE which revealed large polygonal (histiocytes-like) cells
      with copious cytoplasm and large nuclei in the lamina propria of the sigmoid
      colon as well as regenerative epithelial changes. Histopathological assessment of
      biopsies from the same areas confirmed the endomicroscopical findings: Periodic
      acid-Schiff- and CD68-positive foamy histiocytes in the colonic lamina propria
      and an advanced epithelial recovery. Since stool microbiology was repeatedly
      negative and polymerase chain reaction-analysis from colonic biopsies could not
      detect any mRNA for Thropheryma whippleii and common pathogens, we interpreted
      this particular setting as a mucosal healing process after consecutive
      Clostridium difficile infections. In conclusion, by describing these colonic
      histiocytes, we highlight the clinical usefulness of CLE in describing the entity
      of histiocytes in vivo and in real-time during the process of post-infectious
      mucosal healing in the colon.

PMID- 22969213
TI  - Candida-associated gastric ulcer relapsing in a different position with a
      different appearance.
AB  - An 87-year-old, Japanese woman was shown to have a submucosal tumor-like lesion
      with a deep, central ulceration covered with thick, whitish exudate in the
      stomach. Biopsy showed Candida tropicalis but not Helicobacter pylori (H.
      pylori). She had no predisposing factors or history of peptic ulcers nor had
      taken non-steroidal anti-inflammatory drugs (NSAIDs), diagnosed with Candida
      associated gastric ulcer. Though cured of the lesion, she developed another ulcer
      in a different position, in which Candida was demonstrated but H. pylori was
      undetectable. This is the first case of recurrent Candida-associated gastric
      ulcer in the world. Detected in both the original and recurrent lesions in an H.
      pylori-negative patient with no antecedent ulcers who had not taken NSAIDs,
      Candida is considered, contrary to the prevailing opinion, to play an etiologic
      role in ulcer formation.

PMID- 22969214
TI  - "Passive-bending colonoscope" significantly improves cecal intubation in
      difficult cases.
AB  - Colonoscopy sometimes causes pain during insertion, especially in difficult
      cases. Over-insufflation of air causes elongation or acute angulations of the
      colon, making passage of the scope difficult and causing pain. We previously
      reported a sedative-risk-free colonoscopy insertion technique, namely, "Water
      Navigation Colonoscopy". Complete air suction after water infusion not only
      improves the vision, but also makes water flow down to the descending colon,
      while the sigmoid colon collapses and shortens. While non-sedative colonoscopy
      can be carried out without pain in most cases, some patients do complain of pain.
      Most of these patients have abnormal colon morphology, and the pain is caused
      while negotiating the "hairpin" bends of the colon. The "hairpin" bends of the
      colon should be negotiated by gently pushing the full-angled colonoscope. The
      proximal 10-20 cm from the angulated part of the conventional colonoscope is
      stiff, with a wide turning radius, therefore, a conventional colonoscope cannot
      be negotiated through the "hairpin" bends of the colon without stretching them
      and causing pain. The "passive-bending colonoscope" has a flexible tip with a
      narrow turning radius, so that the scope can be negotiated through the "hairpin"
      bends of the colon with a minimum turning radius and minimal discomfort.
      Therefore, the intubation and pain-reducing performance of the "passive-bending
      colonoscope" was assessed in difficult cases.

PMID- 22969215
TI  - Role of taxanes in pancreatic cancer.
AB  - Pancreatic cancer is one of the most deadly cancers and is characterized by a
      poor prognosis. Single agent gemcitabine, despite its limited activity and modest
      impact on disease outcome, is considered as the standard therapy in pancreatic
      cancer. Most of the combination regimens used in the treatment of this disease,
      also including the targeted agents, did not improve the outcome of patients.
      Also, taxanes have been tested as single agent and in combination chemotherapy,
      both in first line and as salvage chemotherapy, as another possible option for
      treating pancreatic cancer. The inclusion of taxanes in combination with
      gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes,
      and above all, new generation taxanes, appear to be suitable candidates for
      further testing to assess their role against pancreatic cancer in various
      clinical settings.

PMID- 22969216
TI  - Confounding factors affect the pathophysiology of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is a newly diagnosed esophageal disease in adult and
      children. The clinical and pathological characteristics of this disease have been
      established and were recently summarized in the expert clinical guideline
      published in 2011. In spite of the wide knowledge accumulated on this disease,
      there are many areas where scientific data are missing, especially in regard to
      the disease's pathophysiology. Recent publications have suggested that other
      confounding factors modify the disease and may affect its clinical-phenotypic
      presentation. Those factors may include place of living, air pollution, race,
      genetic factors and other. In the present report we discussed and review those
      confounding factors, the new developments, and what direction we should go to
      further advance our knowledge of this disease.

PMID- 22969217
TI  - Diagnostic criteria for autoimmune hepatitis in children: a challenge for
      pediatric hepatologists.
AB  - Autoimmune hepatitis (AIH) is a progressive inflammatory liver disorder that is
      rare in children and adolescents. AIH has a broad clinical spectrum and a quick
      response to treatment with corticosteroids and immunosuppressive medication. The
      available diagnosis criteria have limitations and should be evaluated in
      pediatric populations. Recently, some studies reported that the 2008 simplified
      diagnostic criteria for AIH could be used in children with high sensibility and
      specificity. In addition, the authors reported that globulin and immunoglobulin G
      levels can be used interchangeably for diagnostic purposes. They also
      demonstrated that the 2008 simplified criteria fail in identifying patients with
      fulminant hepatic failure. Here, we discuss the limitations of the use of these
      criteria in pediatric patients and the requirement of more studies to improve the
      diagnosis of AIH in children.

PMID- 22969219
TI  - Opposite fates of fructose in the development of metabolic syndrome.
AB  - This short review comments on the recently published work of Ishimoto et al
      regarding the opposing effects of fructokinase C and A isoforms on fructose
      induced metabolic syndrome in mice. The framework for the commentary is the
      preexisting background of epidemiological and experimental data regarding the
      association between ingestion of fructose, as present in sweetened beverages, and
      the development of metabolic syndrome. The work of Ishimoto et al clearly
      confirms the negative effect of fructose on lipid and glucose metabolism,
      independently from the amount of energy provided by the ingested sugar. It also
      confirms the absolute requirement of liver fructose metabolism, driven by
      fructokinase activity, in order to develop the full spectrum of metabolic
      syndrome alterations.

PMID- 22969218
TI  - Asymptomatic pancreatic lesions: new insights and clinical implications.
AB  - Despite great efforts in experimental and clinical research, the prognosis of
      pancreatic cancer (PC) has not changed significantly for decades. Detection of
      pre-invasive lesions or early-stage PC with small resectable cancers in
      asymptomatic individuals remains one of the most promising approaches to
      substantially improve the overall outcome of PC. Therefore, screening programs
      have been proposed to identify curable lesions especially in individuals with a
      familial or genetic predisposition for PC. In this regard, Canto et al recently
      contributed an important article comparing computed tomography, magnetic
      resonance imaging, and endoscopic ultrasound for the screening of 216
      asymptomatic high-risk individuals (HRI). Pancreatic lesions were detected in 92
      of 216 asymptomatic HRI (42.6%). The high diagnostic yield in this study raises
      several questions that need to be answered of which two will be discussed in
      detail in this commentary: First: which imaging test should be performed? Second
      and most importantly: what are we doing with incidentally detected pancreatic
      lesions? Which ones can be observed and which ones need to be resected?

PMID- 22969220
TI  - Entry of hepatitis C virus into the cell: a therapeutic target.
AB  - Several receptors have been identified as implicated on viral entry into the
      hepatocyte; and, this interaction between the virus and potential receptors could
      modulate infection, spontaneous viral clearance, persistence of the infection and
      the widespread of the virus as outbreak. Nevertheless, the playing role of each
      of them remains controversial. The Niemann-Pick type C1 like 1 gene (NPC1L1)
      receptor has been recently implicated on hepatitis C virus (HCV) entry into the
      cell and ezetimibe, an anti-cholesterol drug seems to block that, emerging the
      idea to control hepatitis C outbreak modulating lipid-related receptors.
      Hepatitis C infection seems to modulate lipid metabolism according to host
      genetic background. Indeed, it circulates like a lipoviroparticle. The main aim
      of this field of vision would be to discuss the role of hepatocyte receptors
      implicated on virus entry, especially NPC1L1 and the therapeutic options derived
      from the better knowledge about HCV-lipids- receptors interaction.

PMID- 22969221
TI  - Early administration of branched-chain amino acid granules.
AB  - The effect of malnutrition on survival in patients with decompensated liver
      cirrhosis has not been well defined. Nutritional intervention with branched-chain
      amino acid (BCAA) can increase serum albumin concentration in patients with
      decompensated cirrhosis but its effects on survival are unclear. The BCAA to
      tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between
      4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in
      patients with decompensated liver cirrhosis, and BCAA inhibits hepatic
      carcinogenesis in patients with compensated cirrhosis. This review discusses data
      regarding the effect of early administration of BCAA granules based on the ratio
      of BCAA to BTR on prognosis in patients with cirrhosis.

PMID- 22969223
TI  - Surveillance for gastrointestinal malignancies.
AB  - Gastrointestinal (GI) malignancies are notorious for frequently progressing to
      advanced stages even in the absence of serious symptoms, thus leading to delayed
      diagnoses and dismal prognoses. Secondary prevention of GI malignancies through
      early detection and treatment of cancer-precursor/premalignant lesions,
      therefore, is recognized as an effective cancer prevention strategy. In order to
      efficiently detect these lesions, systemic application of screening tests
      (surveillance) is needed. However, most of the currently used non-invasive
      screening tests for GI malignancies (for example, serum markers such as alpha
      fetoprotein for hepatocellular carcinoma, and fecal occult blood test, for colon
      cancer) are only modestly effective necessitating the use of highly invasive
      endoscopy-based procedures, such as esophagogastroduodenoscopy and colonoscopy
      for screening purposes. Even for hepatocellular carcinoma where non-invasive
      imaging (ultrasonography) has become a standard screening tool, the need for
      repeated liver biopsies of suspicious liver nodules for histopathological
      confirmation can't be avoided. The invasive nature and high-cost associated with
      these screening tools hinders implementation of GI cancer screening programs.
      Moreover, only a small fraction of general population is truly predisposed to
      developing GI malignancies, and indeed needs surveillance. To spare the average
      risk individuals from superfluous invasive procedures and achieve an economically
      viable model of cancer prevention, it's important to identify cohorts in general
      population that are at substantially high risk of developing GI malignancies
      (risk-stratification), and select suitable screening tests for surveillance in
      these cohorts. We herein provide a brief overview of such high-risk cohorts for
      different GI malignancies, and the screening strategies that have commonly been
      employed for surveillance purpose in them.

PMID- 22969222
TI  - Donation after cardio-circulatory death liver transplantation.
AB  - The renewed interest in donation after cardio-circulatory death (DCD) started in
      the 1990s following the limited success of the transplant community to expand the
      donation after brain-death (DBD) organ supply and following the request of
      potential DCD families. Since then, DCD organ procurement and transplantation
      activities have rapidly expanded, particularly for non-vital organs, like
      kidneys. In liver transplantation (LT), DCD donors are a valuable organ source
      that helps to decrease the mortality rate on the waiting lists and to increase
      the availability of organs for transplantation despite a higher risk of early
      graft dysfunction, more frequent vascular and ischemia-type biliary lesions,
      higher rates of re-listing and re-transplantation and lower graft survival, which
      are obviously due to the inevitable warm ischemia occurring during the
      declaration of death and organ retrieval process. Experimental strategies
      intervening in both donors and recipients at different phases of the
      transplantation process have focused on the attenuation of ischemia-reperfusion
      injury and already gained encouraging results, and some of them have found their
      way from pre-clinical success into clinical reality. The future of DCD-LT is
      promising. Concerted efforts should concentrate on the identification of suitable
      donors (probably Maastricht category III DCD donors), better donor and recipient
      matching (high risk donors to low risk recipients), use of advanced organ
      preservation techniques (oxygenated hypothermic machine perfusion, normothermic
      machine perfusion, venous systemic oxygen persufflation), and pharmacological
      modulation (probably a multi-factorial biologic modulation strategy) so that DCD
      liver allografts could be safely utilized and attain equivalent results as DBD
      LT.

PMID- 22969224
TI  - Management of chronic hepatitis B in pregnancy.
AB  - Pregnancy associated with chronic hepatitis B (CHB) is a common and important
      problem with unique challenges. Pregnant women infected with CHB are different
      from the general population, and their special problems need to be considered:
      such as the effect of hepatitis B virus (HBV) infection on the mother and fetus,
      the effect of pregnancy on replication of the HBV, whether mothers should take
      HBV antiviral therapy during pregnancy, the effect of these treatments on the
      mother and fetus, how to carry out immunization of neonates, whether it can
      induce hepatitis activity after delivery and other serious issues. At present,
      there are about 350 million individuals with HBV infection worldwide, of which
      50% were infected during the perinatal or neonatal period, especially in HBV
      endemic countries. Currently, the rate of HBV infection in the child-bearing age
      group is still at a high level, and the infection rate is as high as 8.16%.
      Effective prevention of mother-to-child transmission is an important means of
      reducing the global burden of chronic HBV infection. Even after adopting the
      combined immunization measures, there are still 5%-10% of babies born with HBV
      infection in hepatitis B e antigen positive pregnant women. As HBV perinatal
      transmission is the main cause of chronic HBV infection, we must consider how to
      prevent this transmission to reduce the burden of HBV infection. In this
      population of chronic HBV infected women of childbearing age, specific detection,
      intervention and follow-up measures are particularly worthy of attention and
      discussion.

PMID- 22969225
TI  - Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in
      primary gastric adenocarcinomas.
AB  - AIM: To investigate the genomic copy number alterations that may harbor key
      driver genes in gastric tumorigenesis. METHODS: Using high-resolution array
      comparative genomic hybridization (CGH), we investigated the genomic alterations
      of 20 advanced primary gastric adenocarcinomas (seventeen tubular and three
      mucinous) of Chinese patients from the Jilin province. Ten matching adjacent
      normal regions from the same patients were also studied. RESULTS: The most
      frequent imbalances detected in these cancer samples were gains of 3q26.31-q27.2,
      5p, 8q, 11p, 18p, 19q and 20q and losses of 3p, 4p, 18q and 21q. The use of high
      resolution array CGH increased the resolution and sensitivity of the observed
      genomic changes and identified focal genetic imbalances, which included 54 gains
      and 16 losses that were smaller than 1 Mb in size. The most interesting focal
      imbalances were the intergenic loss/homozygous deletion of the fragile histidine
      triad gene and the amplicons 11q13, 18q11.2 and 19q12, as well as the novel
      amplicons 1p36.22 and 11p15.5. CONCLUSION: These regions, especially the focal
      amplicons, may harbor key driver genes that will serve as biomarkers for either
      the diagnosis or the prognosis of gastric cancer, and therefore, a large-scale
      investigation is recommended.

PMID- 22969226
TI  - FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine
      and platinum-salts.
AB  - AIM: To evaluate the efficacy and safety of the FOLFIRI regimen in patients with
      metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and
      platinum salts. METHODS: All consecutive patients with histologically confirmed,
      metastatic PAC and World Health Organization performance status (PS) <= 2
      received FOLFIRI-1 [irinotecan 180 mg/m(2) on day 1 and leucovorin 400 mg/m(2)
      followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus, then 5-FU 2400 mg/m(2) as a
      46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m(2) on day 1 and
      leucovorin 400 mg/m(2), then 5-FU 2400 mg/m(2) as a 46-h infusion and irinotecan
      100 mg/m(2) repeated on day 3, biweekly) after failure of gemcitabine and
      platinum-based chemotherapies as a systematic policy in two institutions between
      January 2005 and May 2010. Tumor response, time to progression (TTP), overall
      survival rate (OS) and grade 3-4 toxicities were retrospectively studied.
      Subgroup analyses were performed to search for prognostic factors. RESULTS: Sixty
      three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9%
      were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had
      liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n =
      19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained
      with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480
      cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for
      discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved
      in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with
      FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95%
      CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen
      patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or
      digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic
      death. PS 2 was significantly associated with poor TTP [hazard ratio (HR):
      16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004). CONCLUSION: The FOLFIRI
      regimen had an acceptable toxicity and an interesting efficacy in our study,
      limited to patients in good condition (PS 0-1).

PMID- 22969227
TI  - Efficacy of a therapeutic strategy for eradication of Helicobacter pylori
      infection.
AB  - AIM: To determine the efficacy of our therapeutic strategy for Helicobacter
      pylori (H. pylori) eradication and to identify predictive factors for successful
      eradication. METHODS: From April 2006 to June 2010, we retrospectively assessed
      2428 consecutive patients (1025 men, 1403 women; mean age 55 years, age range 18
      92 years) with gastric histology positive for H. pylori infection referred to our
      unit for 13-C urea breath test (UBT), after first-line therapy with proton pump
      inhibitor (PPI) b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d.
      for 7 d. Patients who were still positive to UBT were recommended a second-line
      therapy (PPI b.i.d. + amoxicillin 1 g b.i.d. + tinidazole 500 mg b.i.d. for 14
      d). Third choice treatment was empirical with PPI b.i.d. + amoxicillin 1 g b.i.d.
      + levofloxacin 250 mg b.i.d. for 14 d. RESULTS: Out of 614 patients, still H.
      pylori-positive after first-line therapy, only 326 and 19 patients respectively
      rechecked their H. pylori status by UBT after the suggested second and third-line
      regimens. "Per protocol" eradication rates for first, second and third-line
      therapy were 74.7% (95% CI: 72.7%-76.4%), 85.3% (95% CI: 81.1%-89.1%) and 89.5%
      (95% CI: 74.9%-103%) respectively. The overall percentage of patients with H.
      pylori eradicated after two treatments was 97.8% (95% CI: 97.1%-98.4%), vs 99.9%
      (95% CI: 99.8%-100%) after three treatments. The study found that eradication
      therapy was most effective in patients with ulcer disease (P < 0.05, P = 0.028),
      especially in those with duodenal ulcer. Smoking habits did not significantly
      affect the eradication rate. CONCLUSION: First-line therapy with amoxicillin and
      clarithromycin produces an H. pylori eradication rate comparable or superior to
      other studies and second-line treatment can still be triple therapy with
      amoxicillin and tinidazole.

PMID- 22969228
TI  - Lack of CD44 variant 6 expression in rectal cancer invasive front associates with
      early recurrence.
AB  - AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous
      adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer
      samples from 214 patients treated with short-course radiotherapy (RT, n = 90),
      long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with
      immunohistochemistry for CD44v6. The extent and intensity of membranous and
      cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern,
      were analyzed. RESULTS: Membranous CD44v6 expression was seen in 84% and
      cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous
      CD44v6 expression, the staining pattern in the invasive front was determined as
      "front-positive" and in 41% as "front-negative". The latter pattern was
      associated with narrower circumferential margin (P = 0.01), infiltrative growth
      pattern (P < 0.001), and shorter disease-free survival in univariate survival
      analysis (P = 0.022) when compared to the "front-positive" tumors. CONCLUSION:
      The lack of membranous CD44v6 in the rectal cancer invasive front could be used
      as a method to identify patients at increased risk for recurrent disease.

PMID- 22969229
TI  - Characteristics of intestinal pseudo-obstruction in patients with mitochondrial
      diseases.
AB  - AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal
      pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between
      January 2000 and December 2010, 31 patients (13 males and 18 females) were
      diagnosed with mitochondrial diseases at our hospital. We conducted a
      retrospective review of the patients' sex, subclass of mitochondrial disease, age
      at onset of mitochondrial disease, frequency of CIP and the age at its onset, and
      the duration of survival. The age at onset or at the first diagnosis of the
      disorder that led to the clinical suspicion of mitochondrial disease was also
      examined. RESULTS: Twenty patients were sub-classified with mitochondrial
      encephalopathy with lactic acidosis and stroke-like episodes (MELAS), 8 with
      chronic progressive external ophthalmoplegia (CPEO), and 3 with myoclonus
      epilepsy associated with ragged-red fibers (MERRF). Nine patients were diagnosed
      with CIP, 8 of the 20 (40.0%) patients with MELAS, 0 of the 8 (0.0%) patients
      with CPEO, and 1 of the 3 (33.3%) patients with MERRF. The median age (range) at
      the diagnosis and the median age at onset of mitochondrial disease were 40 (17
      69) and 25 (12-63) years in patients with CIP, and 49 (17-81) and 40 (11-71)
      years in patients without CIP. During the survey period, 5 patients (4 patients
      with MELAS and 1 with CPEO) died. The cause of death was cardiomyopathy in 2
      patients with MELAS, cerebral infarction in 1 patient with MELAS, epilepsy and
      aspiration pneumonia in 1 patient with MELAS, and multiple metastases from
      gastric cancer and aspiration pneumonia in 1 patient with CPEO. CONCLUSION:
      Patients with CIP tend to have disorders that are suspected to be related to
      mitochondrial diseases at younger ages than are patients without CIP.

PMID- 22969230
TI  - Effect of composite yogurt enriched with acacia fiber and Bifidobacterium lactis.
AB  - AIM: To investigate whether composite yogurt with acacia dietary fiber and
      Bifidobacterium lactis (B. lactis) has additive effects in irritable bowel
      syndrome (IBS). METHODS: A total of 130 patients were randomly allocated to
      consume, twice daily for 8 wk, either the composite yogurt or the control
      product. The composite yogurt contained acacia dietary fiber and high-dose B.
      lactis together with two classic yogurt starter cultures. Patients were evaluated
      using the visual analog scale via a structured questionnaire administered at
      baseline and after treatment. RESULTS: Improvements in bowel habit satisfaction
      and overall IBS symptoms from baseline were significantly higher in the test
      group than in the control group (27.16 vs 15.51, P = 0.010, 64.2 +/- 17.0 vs 50.4
      +/- 20.5, P < 0.001; respectively). In constipation-predominant IBS, improvement
      in overall IBS symptoms was significantly higher in the test group than in the
      control group (72.4 +/- 18.4 vs 50.0 +/- 21.8, P < 0.001). In patients with
      diarrhea-predominant IBS, improvement in bowel habit satisfaction from baseline
      was significantly higher in the test group than in the control group (32.90 vs
      7.81, P = 0.006). CONCLUSION: Our data suggest that composite yogurt enriched
      with acacia fiber and B. lactis has greater therapeutic effects in patients with
      IBS than standard yogurt.

PMID- 22969231
TI  - Reduction of gastrointestinal motility by unilateral thyroparathyroidectomy plus
      subdiaphragmatic vagotomy in rats.
AB  - AIM: To investigate whether the combined methods of unilateral
      thyroparathyroidectomy (TPX) and subdiaphragmatic vagotomy (VAX) can be adapted
      for rats and used as a reliable method to produce a rat model of long-term
      reduction of gastrointestinal (GI) motor function. METHODS: Male Sprague-Dawley
      rats were randomly divided into 3 groups, normal, sham-operated and unilateral
      TPX plus VAX. The TPX plus VAX rats received VAX 7 d after application of TPX,
      and dietary intake and fecal output were then measured daily for 1 wk. After
      completion of the experiments, gastric emptying and small bowel transit were
      measured in vivo, and the contractile responses of colonic strips to excitatory
      and inhibitory neurotransmitters were estimated using isometric force transducers
      in vitro. RESULTS: In comparison with normal and sham-operated rats, rats which
      received unilateral TPX plus VAX showed a significant decrease in body weight and
      in fecal pellet number and weight throughout the entire week. Application of TPX
      plus VAX to rats markedly delayed gastric emptying and small bowel transit. In
      TPX plus VAX rats, the longitudinal muscles of the proximal colon showed a
      significant reduction in contractile responses to acetylcholine (5 * 10(-6)
      mol/L), and a dramatic attenuation of contractile responses was also observed in
      both the longitudinal and circular muscles of the distal colon. However, the
      spontaneous contractility of the colonic strips from TPX plus VAX rats was not
      significantly affected by treatment with N-nitro-L-arginine-methyl ester (0.1
      mol/L). CONCLUSION: The results indicate that unilateral TPX plus VAX reduced the
      motor function of the GI tract in rats, and the reduced gut motility is likely
      mediated, at least in part, by inhibition of the excitatory neurotransmitter
      system.

PMID- 22969232
TI  - Does immunohistochemical staining have a clinical impact in early gastric cancer
      conducted endoscopic submucosal dissection?
AB  - AIM: To evaluate clinicopathologic parameters and the clinical significance
      related lymphovascular invasion (LVI) by immunohistochemical staining (IHCS) in
      endoscopic submucosal dissection (ESD). METHODS: Between May 2005 and May 2010, a
      total of 348 lesions from 321 patients (mean age 63 +/- 10 years, men 74.6%) with
      early gastric cancer (EGC) who met indication criteria after ESD were analyzed
      retrospectively. The 348 lesions were divided into the absolute (n = 100,
      differentiated mucosal cancer without ulcer <= 20 mm) and expanded (n = 248)
      indication groups after ESD. The 248 lesions were divided into four subgroups
      according to the expanded ESD indication. The presence of LVI was determined by
      factor VIII-related antigen and D2-40 assessment. We compared LVI IHCS-negative
      group with LVI IHCS-positive in each group. RESULTS: LVI by hematoxylin-eosin
      staining (HES) and IHCS were all negative in the absolute group, while was
      observed in only the expanded groups. The positive rate of LVI by IHCS was higher
      than that of LVI by HES (n = 1, 0.4% vs n = 11, 4.4%, P = 0.044). LVI IHCS
      positivity was observed when the cancer invaded to the mucosa 3 (M3) or submucosa
      1 (SM1) levels, with a predominance of 63.6% in the subgroup that included only
      SM1 cancer (P < 0.01). In a univariate analysis, M3 or SM1 invasion by the tumor
      was significantly associated with a higher rate of LVI by IHCS, but no factor was
      significant in a multivariate analysis. There were no cases of tumor recurrence
      or metastasis during the median 26 mo follow-up. CONCLUSION: EGCs of the absolute
      group are immunohistochemically stable. The presence of LVI may be carefully
      examined by IHCS in an ESD expanded indication group with an invasion depth of M3
      or greater.

PMID- 22969233
TI  - Spectral analysis of bowel sounds in intestinal obstruction using an electronic
      stethoscope.
AB  - AIM: To determine the value of bowel sounds analysis using an electronic
      stethoscope to support a clinical diagnosis of intestinal obstruction. METHODS:
      Subjects were patients who presented with a diagnosis of possible intestinal
      obstruction based on symptoms, signs, and radiological findings. A 3MTM
      Littmann((r)) Model 4100 electronic stethoscope was used in this study. With the
      patients lying supine, six 8-second recordings of bowel sounds were taken from
      each patient from the lower abdomen. The recordings were analysed for sound
      duration, sound-to-sound interval, dominant frequency, and peak frequency.
      Clinical and radiological data were reviewed and the patients were classified as
      having either acute, subacute, or no bowel obstruction. Comparison of bowel sound
      characteristics was made between these subgroups of patients. In the presence of
      an obstruction, the site of obstruction was identified and bowel calibre was also
      measured to correlate with bowel sounds. RESULTS: A total of 71 patients were
      studied during the period July 2009 to January 2011. Forty patients had acute
      bowel obstruction (27 small bowel obstruction and 13 large bowel obstruction), 11
      had subacute bowel obstruction (eight in the small bowel and three in large
      bowel) and 20 had no bowel obstruction (diagnoses of other conditions were made).
      Twenty-five patients received surgical intervention (35.2%) during the same
      admission for acute abdominal conditions. A total of 426 recordings were made and
      420 recordings were used for analysis. There was no significant difference in
      sound-to-sound interval, dominant frequency, and peak frequency among patients
      with acute bowel obstruction, subacute bowel obstruction, and no bowel
      obstruction. In acute large bowel obstruction, the sound duration was
      significantly longer (median 0.81 s vs 0.55 s, P = 0.021) and the dominant
      frequency was significantly higher (median 440 Hz vs 288 Hz, P = 0.003) when
      compared to acute small bowel obstruction. No significant difference was seen
      between acute large bowel obstruction and large bowel pseudo-obstruction. For
      patients with small bowel obstruction, the sound-to-sound interval was
      significantly longer in those who subsequently underwent surgery compared with
      those treated non-operatively (median 1.29 s vs 0.63 s, P < 0.001). There was no
      correlation between bowel calibre and bowel sound characteristics in both acute
      small bowel obstruction and acute large bowel obstruction. CONCLUSION:
      Auscultation of bowel sounds is non-specific for diagnosing bowel obstruction.
      Differences in sound characteristics between large bowel and small bowel
      obstruction may help determine the likely site of obstruction.

PMID- 22969234
TI  - Stopping or reducing dietary fiber intake reduces constipation and its associated
      symptoms.
AB  - AIM: To investigate the effect of reducing dietary fiber on patients with
      idiopathic constipation. METHODS: Sixty-three cases of idiopathic constipation
      presenting between May 2008 and May 2010 were enrolled into the study after
      colonoscopy excluded an organic cause of the constipation. Patients with previous
      colon surgery or a medical cause of their constipation were excluded. All
      patients were given an explanation on the role of fiber in the gastrointestinal
      tract. They were then asked to go on a no fiber diet for 2 wk. Thereafter, they
      were asked to reduce the amount of dietary fiber intake to a level that they
      found acceptable. Dietary fiber intake, symptoms of constipation, difficulty in
      evacuation of stools, anal bleeding, abdominal bloating or abdominal pain were
      recorded at 1 and 6 mo. RESULTS: The median age of the patients (16 male, 47
      female) was 47 years (range, 20-80 years). At 6 mo, 41 patients remained on a no
      fiber diet, 16 on a reduced fiber diet, and 6 resumed their high fiber diet for
      religious or personal reasons. Patients who stopped or reduced dietary fiber had
      significant improvement in their symptoms while those who continued on a high
      fiber diet had no change. Of those who stopped fiber completely, the bowel
      frequency increased from one motion in 3.75 d (+/- 1.59 d) to one motion in 1.0 d
      (+/- 0.0 d) (P < 0.001); those with reduced fiber intake had increased bowel
      frequency from a mean of one motion per 4.19 d (+/- 2.09 d) to one motion per 1.9
      d (+/- 1.21 d) on a reduced fiber diet (P < 0.001); those who remained on a high
      fiber diet continued to have a mean of one motion per 6.83 d (+/- 1.03 d) before
      and after consultation. For no fiber, reduced fiber and high fiber groups,
      respectively, symptoms of bloating were present in 0%, 31.3% and 100% (P < 0.001)
      and straining to pass stools occurred in 0%, 43.8% and 100% (P < 0.001).
      CONCLUSION: Idiopathic constipation and its associated symptoms can be
      effectively reduced by stopping or even lowering the intake of dietary fiber.

PMID- 22969235
TI  - Gastric mucin expression in Helicobacter pylori-related, nonsteroidal anti
      inflammatory drug-related and idiopathic ulcers.
AB  - AIM: To determine the pattern of secreted mucin expression in Helicobacter pylori
      (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and
      idiopathic gastric ulcers. METHODS: We randomly selected 92 patients with H.
      pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and
      NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric
      ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, and for mucin 5AC
      (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the
      ulcer margin. Inflammation score was assessed according to the Sydney system.
      RESULTS: MUC5AC was expressed on the surface epithelium (98.9%) and neck glands
      (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly
      expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and
      absent in the surface epithelium (0%). The pattern of mucin expression in
      idiopathic ulcer margins was not different from the expression in ulcers
      associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8
      ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers
      are associated with hospitalized patients and have higher bleeding and mortality
      rates. CONCLUSION: Idiopathic ulcers have a unique clinical profile. Gastric
      mucin expression in idiopathic gastric ulcers is unchanged compared with H.
      pylori and/or NSAID-associated ulcers.

PMID- 22969236
TI  - What MELD score mandates use of entecavir for ACLF-HBV HBeAg-negative patients?
AB  - AIM: To investigate optimal timing for therapeutic efficacy of entecavir for
      acute-on-chronic hepatitis B liver failure (ACLF-HBV) in hepatitis B e antigen
      (HBeAg)-negative patients. METHODS: A total of 109 inpatients with ACLF-HBV were
      recruited from the Department of Infectious Diseases of the Third Affiliated
      Hospital, Sun Yat-sen University from October 2007 to October 2010. Entecavir 0.5
      mg/d was added to each patient's comprehensive therapeutic regimen. Patients were
      divided into three groups according to model for end-stage liver disease (MELD)
      score: high (>= 30, 20 males and 4 females, mean age 47.8 +/- 13.5 years);
      intermediate (22-30, 49 males and 5 females, 45.9 +/- 12.4 years); and low (<=
      22, 28 males and 3 females, 43.4 +/- 9.4 years). Statistical analysis were
      performed using SPSS 11.0 software. Data with normal distribution were expressed
      as mean +/- SD and comparisons were made with Student's t tests. A value of P <
      0.05 was considered statistically significant. Viral loads were related
      exponentially and logarithmic data were used for analysis. RESULTS: For 24
      patients with MELD score >= 30, treatment lasted 17.2 +/- 16.5 d. Scores before
      and after treatment were significantly different (35.97 +/- 4.87 and 40.48 +/-
      8.17, respectively, t = -2.762, P = 0.011); HBV DNA load was reduced (4.882 +/-
      1.847 copies log(10)/mL to 3.685 +/- 1.436 copies log(10)/mL); and mortality rate
      was 95.83% (23/24). Of 54 patients with scores of 22-30, treatment lasted for
      54.0 +/- 43.2 d; scores before and after treatment were 25.87 +/- 2.33 and 25.82
      +/- 13.92, respectively (t = -0.030, P = 0.976); HBV DNA load decreased from
      6.308 +/- 1.607 to 3.473 +/- 2.097 copies log(10)/mL; and mortality was 51.85%
      (28/54). Of 31 patients with scores <= 22, treatment lasted for 66.1 +/- 41.9 d;
      scores before and after treatment were 18.88 +/- 2.44 and 12.39 +/- 7.80,
      respectively, (t = 4.860, P = 0.000); HBV DNA load decreased from 5.841 +/- 1.734
      to 2.657 +/- 1.154 copies log(10)/mL; and mortality was 3.23% (1/31). CONCLUSION:
      For HBeAg-negative patients with ACLF-HBV, when entecavir was added to
      comprehensive therapy, a MELD score >= 30 predicted very poor prognosis due to
      fatal liver failure.

PMID- 22969237
TI  - Side population cells isolated from KATO III human gastric cancer cell line have
      cancer stem cell-like characteristics.
AB  - AIM: To investigate whether the side population (SP) cells possess cancer stem
      cell-like characteristics in vitro and the role of SP cells in tumorigenic
      process in gastric cancer. METHODS: We analyzed the presence of SP cells in
      different human gastric carcinoma cell lines, and then isolated and identified
      the SP cells from the KATO III human gastric cancer cell line by flow cytometry.
      The clonogenic ability and self-renewal were evaluated by clone and sphere
      formation assays. The related genes were determined by reverse transcription
      polymerase chain reaction. To compare tumorigenic ability, SP and non-side
      population (NSP) cells from the KATO III human gastric cancer cell line were
      subcutaneously injected into nude mice. RESULTS: SP cells from the total
      population accounted for 0.57% in KATO III, 1.04% in Hs-746T, and 0.02% in AGS
      (CRL-1739). SP cells could grow clonally and have self-renewal capability in
      conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different
      between SP and NSP cells. However, there was no apparent difference between SP
      and NSP cells when they were injected into nude mice. CONCLUSION: SP cells have
      some cancer stem cell-like characteristics in vitro and can be used for studying
      the tumorigenic process in gastric cancer.

PMID- 22969238
TI  - 7-difluoromethoxyl-5,4'-di-n-octylgenistein inhibits growth of gastric cancer
      cells through downregulating forkhead box M1.
AB  - AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein
      (DFOG), a novel synthetic genistein analogue, affects the growth of gastric
      cancer cells and its mechanisms. METHODS: A series of genistein analogues were
      prepared by difluoromethylation and alkylation, and human gastric cancer cell
      lines AGS and SGC-7901 cultured in vitro were treated with various concentrations
      of genistein and genistein analogues. The cell viability was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were
      incubated by DFOG at different concentrations. The growth inhibitory effects were
      evaluated using MTT and clonogenic assay. The distribution of the phase in cell
      cycle was analyzed using flow cytometric analysis with propidium iodide staining.
      The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed
      by reverse transcription-polymerase chain reaction and Western blotting. The
      expression levels of CDK1, Cdc25B, cyclin B and p27(KIP1) protein were detected
      using Western blotting. RESULTS: Nine of the genistein analogues had more
      effective antitumor activity than genistein. Among the tested analogues, DFOG
      possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG
      significantly inhibited the cell viability and colony formation of AGS and SGC
      7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase.
      DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1,
      Cdc25B, cyclin B, and increased p27(KIP1) at protein levels. Knockdown of FOXM1
      by small interfering RNA before DFOG treatment resulted in enhanced cell growth
      inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated
      DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the
      growth of human gastric cancer cells by down-regulating the FOXM1 expression.

PMID- 22969239
TI  - A case report of abdominal distention caused by herpes zoster.
AB  - Gastrointestinal complications caused by herpes zoster are extremely rare. Here,
      we described a case of abdominal distention caused by herpes zoster. The patient
      was a 59-year-old female who suffered from unexplained paroxysmal and a burning
      pain on the right part of her waist and abdomen, accompanied by abdominal
      distention. Intestinal pseudo-obstruction was diagnosed by abdominal radiography.
      Distention of the right abdominal wall was still apparent after one month. In
      this report, we found that recovery from abdominal distention caused by herpes
      zoster is difficult and may require surgical intervention.

PMID- 22969240
TI  - Assessing the quality of randomized controlled trials published in the Journal of
      Korean Medical Science from 1986 to 2011.
AB  - Low quality clinical trials have a possibility to have errors in the process of
      deriving the results and therefore distort the study. Quality assessment of
      clinical trial is necessary in order to prevent any clinical application
      erroneous results is important. Randomized controlled trial (RCT) is a design for
      evaluate the effectiveness of medical procedure. This study was conducted by
      extracting the RCTs from the original articles published in the Journal of Korean
      Medical Science (JKMS) from 1986 to 2011 and conducting a qualitative analysis
      using three types of analysis tools: Jadad scale, van Tulder scale and Cochrane
      Collaboration risk of bias Tool. To compare the quality of articles of JKMS,
      quality analysis of the RCTs published in Yonsei Medical Journal (YMJ) and Korean
      Journal of Internal Medicine was also conducted. In the JKMS, YMJ and Korean
      Journal of Internal Medicine, the quantitative increase of RCT presented over
      time was observed but no qualitative improvement of RCT was observed over time.
      From the results of this study, it is required for the researchers to plan for
      and perform higher quality studies.

PMID- 22969241
TI  - Present condition analysis of physician assistant in Korea.
AB  - This study intended to identify the need for the legalization and development of
      a systematic program for physician assistants (PAs) by understanding the actual
      state of PA operation in hospitals. In 114 hospitals assigned as resident
      training hospitals for surgery, a survey was conducted on the personnel working
      as PAs in those hospitals; the survey included general personal information,
      working conditions, training time, and satisfaction. A total of 192 PAs in
      surgery at 35 hospitals responded to the survey. The types of PAs are Surgical
      Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator,
      and Clinical Research Coordinator. Types of work PAs preformed are surgical
      assistance, wound dressing, educating patients, overlooking consultation, doing
      paper works, writing operation records, and confirming examination results which
      were ordered. The satisfaction level for the position which PAs hold were 29.1%
      and and satisfaction level which doctors see towards PA was 15%. The role and the
      job descriptions of PAs are not clear cut, there are many discrepancies among
      hospitals we studied. As a result, legalization and the implementation of
      standardized role of PAs will lead to increase level of satisfactions in the work
      force and the quality of work which PAs perform will be greater.

PMID- 22969242
TI  - Prostaglandin E(2) and interleukin-1beta reduce E-cadherin expression by
      enhancing snail expression in gastric cancer cells.
AB  - Inflammation is closely related to the progression of cancer as well as
      tumorigenesis. Here, we investigated the effect of prostaglandin E(2) (PGE(2))
      and interleukin-1beta (IL-1beta) on E-cadherin expression in SNU719 gastric
      cancer cells. E-cadherin expression decreased as the dose or exposure time of
      PGE(2) and IL-1beta increased, whereas Snail expression increased with dose or
      time of PGE(2) and IL-1beta. E-cadherin expression reduced by PGE(2) treatment
      increased after the transfection of Snail siRNA. Neutralization of IL-1beta using
      anti-IL-1beta antibody blocked the expression pattern of E-cadherin and Snail
      occurred by IL-1beta treatment. However, there was no synergic effect of IL-1beta
      and PGE(2) on the expression pattern of E-cadherin and Snail. In conclusion,
      inflammatory mediators reduced E-cadherin expression by enhancing Snail
      expression in gastric cancer cells. Inflammation-induced transcriptional
      regulation of E-cadherin in gastric cancer has implications for targeted
      chemoprevention and therapy.

PMID- 22969243
TI  - The time between paraquat ingestion and a negative dithionite urine test in an
      independent risk factor for death and organ failure in acute paraquat
      intoxication.
AB  - To identify a prognostic marker that is less sensitive to variations in the
      elapsed time since paraquat ingestion, we assessed the time between paraquat
      ingestion and a negative dithionite urine test as a prognostic parameter in
      patients with acute paraquat intoxication. Forty-one patients with acute paraquat
      intoxication were enrolled in this study and analyzed to verify significant
      determinants of mortality and organ dysfunction. The amount of paraquat ingested,
      paraquat plasma levels, and the time to a negative urine dithionite test were
      significant independent risk factors predicting mortality. The amount of paraquat
      ingestion, and the time to a negative urine dithionite test were independent risk
      factors predicting organ dysfunction. With a cut-off value of 34.5 hr for the
      time to negative conversion of the urine dithionite test, the sensitivity and
      specificity for mortality were 71.4% and 75.0%, respectively. The incidence of
      acute kidney injury and respiratory failure above 34.5 hr were 100% and 85.0%,
      respectively. In conclusion, the time to a negative urine dithionite test is the
      reliable marker for predicting mortality and/or essential organ failure in
      patients with acute paraquat intoxication, who survive 72 hr.

PMID- 22969244
TI  - Cancer risk in adult residents near nuclear power plants in Korea - a cohort
      study of 1992-2010.
AB  - This study evaluated cancer risk for adult residents near Nuclear Power Plants
      (NPPs) in Korea through a valid prospective cohort study during 1992-2010. The
      study cohort was composed of 11,367 adults living within a five km radius from
      the NPPs for the exposed and 24,809 adults for the non-exposed or reference
      cohort set at two different levels of proximity; 5-30 km radius and more than 30
      km radius away from NPPs. In 303,542.5 person-years of follow-up, a total of
      2,298 cancer cases of all sites, or 1,377 radio-inducible cancers diagnosed
      during 1992-2008 were ascertained. Multiple adjusted hazard ratios and 95%
      confidence intervals were estimated using multivariate Cox proportional hazard
      model. There were no epidemiological evidence for increased risk of cancer due to
      radiation from NPPs. Radiological study results or surveillance data of radiation
      doses around NPPs could be well documented for risk estimation of radio-inducible
      cancers, instead of epidemiological study results of the long-time required.
      Continuous surveillance of quantitative measures of dose levels around NPPs and
      radiation exposures to the residents is warranted.

PMID- 22969245
TI  - Subpopulations of regulatory T cells in rheumatoid arthritis, systemic lupus
      erythematosus, and Behcet's disease.
AB  - Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and
      activated Treg (aTreg), have been discovered. The authors investigated the
      relationship between the change of Treg, aTreg and rTreg and autoimmune diseases.
      Treg cells and those subpopulations were analyzed by using the human regulatory T
      cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13
      systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls.
      The proportion of Treg cells was significantly lower in RA (3.8% +/- 1.0%) (P <
      0.001) and BD (3.3% +/- 0.5%) (P < 0.01) compared to healthy controls (5.0% +/-
      1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% +/-
      0.2%) (P = 0.008) and BD (0.3% +/- 0.1%) (P = 0.013) compared to healthy controls
      (0.6% +/- 0.3%). The rTreg cells showed no significant differences. The ratio of
      aTreg to rTreg was lower in RA patients (0.4% +/- 0.2%) than that in healthy
      controls (0.7% +/- 0.4%) (P = 0.002). This study suggests that the decrement of
      aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral
      blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations
      would be more informative than total Treg cells in investigating mechanism of
      autoimmune disease.

PMID- 22969246
TI  - Preoperative serum thyroglobulin as a useful predictive marker to differentiate
      follicular thyroid cancer from benign nodules in indeterminate nodules.
AB  - Indeterminate cytology results increase the number of repetitive procedure and
      unnecessary surgery. This study was designed to find useful and simple predictive
      tools to differentiate malignant thyroid nodules from indeterminate nodules. We
      retrospectively enrolled 164 patients who had undergone thyroid surgery as a
      result of indeterminate cytology in the National Cancer Center. We reviewed
      patients' age at diagnosis, sex, preoperative biochemical markers such as
      thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical
      and pathological findings, which were subjected to statistical analysis. We found
      several clinical and sonographical predictive factors that showed significant
      differences. Young age, male, preoperative high Tg level, and hypoechoic nodule
      on sonography all increased cancer probability significantly in multivariate
      analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity
      were 54.8% and 90.1%, respectively (AUC 0.748, P < 0.001). In the case of nodule
      size > 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg >
      70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038).
      Preoperative Tg levels had very high specificity in predicting thyroid cancer in
      case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful
      marker for differentiating thyroid cancer from benign thyroid nodules in the
      cytological diagnosis of indeterminate nodules.

PMID- 22969247
TI  - Effectiveness of [(124)I]-PET/CT and [(18)F]-FDG-PET/CT for localizing recurrence
      in patients with differentiated thyroid carcinoma.
AB  - Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is
      generally encouraging, a diagnostic dilemma is posed when an increasing level of
      serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using
      conventional imaging tools such as the iodine-131 whole-body scanning (the
      [(131)I] scan) or neck ultrasonography (US). The objective of the present study
      was to evaluate the diagnostic value of [(124)I]-PET/CT and [(18)F]-FDG-PET/CT in
      terms of accurate detection of both iodine- and non-iodine-avid recurrence,
      compared with that of conventional imaging such as the [(131)I] scan or neck
      ultrasonography (US). Between July 2009 and June 2010, we prospectively studied
      19 DTC patients with elevated thyroglobulin levels but who do not show
      pathological lesions when conventional imaging modalities are used. All involved
      patients had undergone total thyroidectomy and radioiodine (RI) treatment, and
      who had been followed-up for a mean of 13 months (range, 6-21 months) after the
      last RI session. Combined [(18)F]-FDG-PET/CT and [(124)I]-PET/CT data were
      evaluated for detecting recurrent DTC lesions in study patients and compared with
      those of other radiological and/or cytological investigations. Nine of 19
      patients (47.4%) showed pathological [(18)F]-FDG (5/19, 26.3%) or [(124)I]-PET
      (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients,
      disease management was modified in six (66.7%) and disease was restaged in seven
      (77.8%). In particular, the use of the described imaging combination optimized
      planning of surgical resection to deal with locoregional recurrence in 21.1%
      (4/19) of patients, who were shown to be disease-free during follow-up after
      surgery. Our results indicate that combination of [(18)F]-FDG-PET/CT and [(124)I]
      PET/CT affords a valuable diagnostic method that can be used to make therapeutic
      decisions in patients with DTC who are tumor-free on conventional imaging studies
      but who have high Tg levels.

PMID- 22969248
TI  - Clinicopathologic and molecular characteristics of lung adenocarcinoma arising in
      young patients.
AB  - Lung cancer rarely occurs in young patients. Recent studies have demonstrated
      that epidemiologic data are closely correlated to some molecular characteristics.
      We investigated the clinicopathologic characteristics of lung adenocarcinoma in
      young patients and evaluated immunohistochemically detected epidermal growth
      factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK)
      positivity. Among lung adenocarcinoma patients, 31 cases were of the <= 40 yr-old
      group and 261 cases of > 50 yr-old group. Young patients were more likely to be
      females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high
      TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis
      (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was
      more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2%
      vs 16.5%) in the adenocarcinoma of young patients. There was no significant
      survival difference between the two age groups. The rate of EGFR mutation status
      and ALK positivity did not show a statistical difference between two groups. In
      conclusion, lung adenocarcinoma of young patients demonstrates distinct
      pathologic features with frequent presence of a signet ring cell feature and rare
      occurrence of lepidic growth pattern. Further investigation for other genetic
      abnormalities would be needed.

PMID- 22969249
TI  - Suppressive effect of 19-nor-1alpha-25-dihydroxyvitamin D2 on gastric cancer
      cells and peritoneal metastasis model.
AB  - The active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (calcitriol),
      inhibits the growth of several types of human cancer cells in vitro, but its
      therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19
      nor-1,25-dihydroxyvitamin D(2) (paricalcitol), has fewer calcemic effects and
      exhibits an activity equipotent to that of calcitriol. We assessed the antitumor
      and anti-inflammatory effects of paricalcitol in gastric cancer cells, and
      evaluated the potential role of vitamin D in the treatment of peritoneal
      metastatic gastric cancer. In this study, treatment with paricalcitol inhibited
      gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also
      induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of
      intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol.
      (18)F-FDG uptake was significantly lower in the paricalcitol group compared to
      control group (SUV; control group 13.2 +/- 5.3 vs paricalcitol group 4.5 +/-
      3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol
      treated mice (control group 353.2 +/- 22.9 mm(3) vs paricalcitol group 252.0 +/-
      8.4 mm(3)). These results suggest that the vitamin D analog, paricalcitol, has
      anticancer activity on gastric cancer cells by regulation of the cell cycle,
      apoptosis, and inflammation.

PMID- 22969250
TI  - Index of microcirculatory resistance as predictor for microvascular functional
      recovery in patients with anterior myocardial infarction.
AB  - IMR is useful for assessing the microvascular dysfunction after primary
      percutaneous coronary intervention (PCI). It remains unknown whether index of
      microcirculatory resistance (IMR) reflects the functional outcome in patients
      with anterior myocardial infarction (AMI) with or without microvascular
      obstruction (MO).This study was performed to evaluate the clinical value of the
      IMR for assessing myocardial injury and predicting microvascular functional
      recovery in patients with AMI undergoing primary PCI. We enrolled 34 patients
      with first anterior AMI. After successful primary PCI, the mean distal coronary
      artery pressure (P(a)), coronary wedge pressure (P(cw)), mean aortic pressure
      (P(a)), mean transit time (T(mn)), and IMR (P(d)* hyperemic T(mn)) were measured.
      The presence and extent of MO were measured using cardiac magnetic resonance
      image (MRI). All patients underwent follow-up echocardiography after 6 months. We
      divided the patients into two groups according to the existence of MO (present; n
      = 16, absent; n = 18) on MRI. The extent of MO correlated with IMR (r = 0.754; P
      < 0.001), P(cw) (r = 0.404; P = 0.031), and P(cw)/P(d) of infarct-related
      arteries (r = 0.502; P = 0.016). The IMR was significantly correlated with the
      DeltaRegional wall motion score index (r = -0.61, P < 0.01) and DeltaLeft
      ventricular ejection fraction (r = -0.52, P < 0.01), implying a higher IMR is
      associated with worse functional improvement. Therefore, Intracoronary wedge
      pressures and IMR, as parameters for specific and quantitative assessment of
      coronary microvascular dysfunction, are reliable on-site predictors of short-term
      myocardial viability and Left ventricle functional recovery in patients
      undergoing primary PCI for AMI.

PMID- 22969251
TI  - Mid-term outcomes of total arterial revascularization versus conventional
      coronary surgery in isolated three-vessel coronary disease.
AB  - Whether arterial conduits are superior to venous grafts in coronary artery
      bypassing has been debated. The aim of this study was to investigate clinical
      outcomes after total arterial revascularization versus conventional coronary
      bypassing using both arterial and venous conduits in isolated three-vessel
      coronary disease. Between 2003 and 2005, 503 patients who underwent isolated
      coronary artery bypass grafting for three-vessel coronary disease were enrolled.
      A total of 117 patients underwent total arterial revascularization (Artery group)
      whereas 386 patients were treated with arterial and venous conduits (Vein group).
      Major adverse outcomes (death, myocardial infarction, stroke and repeat
      revascularization) were compared. Clinical follow-up was complete in all patients
      with a mean duration of 6.1 +/- 0.9 yr. After adjustment for differences in
      baseline risk factors, risks of death (hazard ratio [HR] 0.96; 95% confidence
      interval [CI] 0.51-1.82, P = 0.90), myocardial infarction (HR 0.20, 95% CI 0.02
      2.63, P = 0.22), stroke (HR 1.29, 95% CI 0.35-4.72, P = 0.70), repeat
      revascularization (HR 0.64, 95% CI 0.26-1.55, P = 0.32) and the composite
      outcomes (HR 0.83, 95% CI 0.50-1.36, P = 0.45) were similar between two groups.
      Since the use of veins does not increase the risks of adverse outcomes compared
      with total arterial revascularization, a selection of the conduit should be more
      liberal.

PMID- 22969252
TI  - Usefulness of glycated hemoglobin as diagnostic criteria for metabolic syndrome.
AB  - The metabolic syndrome (MetS) is the clustering of cardiovascular risk factors
      and known as a powerful predictor of diabetes and cardiovascular disease.
      Glycated hemoglobin (HbA1c) is used as one of the diagnostic criteria for
      diabetes and category of increased risk for diabetes. We examined the usefulness
      of HbA1c as a diagnostic tool for MetS and to determine the cut-off value of
      HbA1c as a criterion for MetS, in non-diabetic Korean subjects. We analyzed 7,307
      participants (male: 4,181, 57%) in a medical check-up program, and applied the
      newly recommended guidelines of the International Diabetes Federation for
      diagnosis of MetS. The mean HbA1c was 5.54% in all subjects and showed no
      significant difference between genders. Using receiver-operating characteristic
      curve, HbA1c value corresponding to the fasting plasma glucose value of 100 mg/dL
      was 5.65% (sensitivity 52.3%, specificity 76.7%). The prevalence of MetS was 8.5%
      according to the IDF guideline and 10.9% according to HbA1c value of 5.7%,
      showing 69.5% agreement rate. The detection rate of MetS increased to 25.7% using
      the HbA1c criterion of 5.7% instead of fasting hyperglycemia. This study suggests
      that HbA1c might be used as a diagnostic criterion for MetS and the appropriate
      cut-off value of HbA1c may be 5.65% in this Korean population.

PMID- 22969253
TI  - Association of endotoxins and colon polyp: a case-control study.
AB  - Endotoxins are known to be associated with the occurrence of various chronic
      diseases. This study was conducted to investigate the role of endotoxins in the
      pathogenesis of colon polyps through a case-control study. A total of 145
      subjects (74 subjects in the polyp group and 71 subjects in the control group)
      had undergone a colonoscopy. Age, body mass index (BMI) and endotoxin levels were
      found to be significantly higher in the polyp group than in the control group.
      The endotoxin level was still significantly higher in the polyp group than in the
      control group, even after age and BMI had been adjusted (polyp group 0.108 +/-
      0.007 EU/mL, control group 0.049 +/- 0.008 EU/mL, P < 0.001). In subgroup
      analysis, the endotoxin level significantly increased in accordance with the
      number of colon polyps (one-polyp group, 0.088 +/- 0.059 EU/mL; two-polyp group,
      0.097 +/- 0.071 EU/mL; three-or-more-polyp group, 0.149 +/- 0.223 EU/mL). The
      endotoxin levels also significantly increased in groups with tubular adenoma with
      high-grade dysplasia (hyperplastic polyp group, 0.109 +/- 0.121 EU/mL; tubular
      adenoma with low grade dysplasia group, 0.103 +/- 0.059 EU/mL; tubular adenoma
      with high grade dysplasia group, 2.915 +/- 0.072 EU/mL). In conclusion, the serum
      level of endotoxins is quantitatively correlated with colon polyps.

PMID- 22969254
TI  - Clinical results of high-dose chemotherapy followed by autologous peripheral
      blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.
AB  - Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in
      treatment of advanced stage of RMS in children are still dismal. Recently, high
      dose chemotherapy followed by autologous peripheral blood stem cell
      transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS
      patients. We investigated the effectiveness of HDC/APBSCT by reviewing the
      clinical records of high-risk pediatric RMS patients in single institute
      database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at
      the time of first diagnosis. These patients were classified as two groups
      according to treatment method. The first group was HDC/APBSCT and the other was
      conventional multi-agent chemotherapy group. Differences of clinical results
      between the two groups were analyzed. The median age of patients was 5 yr,
      ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all
      patients was 24.8% +/- 4.8%. HDC/APBSCT group and conventional multi-agent
      chemotherapy group were 41.3% +/- 17.8% and 16.7% +/- 7.6% for 5-yr EFS,
      respectively (P = 0.023). There was a significant difference in the result of
      HDC/APBSCT between complete remission or very good partial response group and
      poor response group (50% +/- 20.4% vs 37.5% +/- 28.6%, P = 0.018). HDC/APBSCT can
      be a promising treatment modality in high-risk RMS patients.

PMID- 22969255
TI  - Early sustained injections of erythropoietin improve angiogenesis and restoration
      of perfusion in the ischemic mouse hindlimb.
AB  - This study was conducted to investigate the effects of erythropoietin (Epo) on
      both acute and chronic limb ischemia (ALI and CLI) and to evaluate the
      differences in mechanisms according to the method of Epo administration. Hindlimb
      ischemia was made in BALB/c mice with femoral artery ligation. The mice were
      divided into four groups: Group 1 (control, no treatment), Group 2 (ALI, early
      multiple doses), Group 3 (ALI, early single high dose), Group 4 (CLI, late
      multiple doses). Blood flow ratio significantly increased in Group 2 in 4 weeks.
      Expression of pAkt and Erythropoietin receptor were significantly higher in Group
      2 on postoperative day (POD) 7. The number of CD31- and vascular endothelial
      growth factor-positive cells were significantly higher in Group 2 on POD 7 and
      56. Group 3 and 4 showed a tendency of higher cell counts than the control. The
      early sustained Epo was effective in improving blood flow through angiogenesis.
      In chronic phase, weekly multiple dosing of Epo induced angiogenesis, however,
      the blood flow ratio did not increase significantly. The results of this study
      suggest that Epo administration during the acute phase followed by maintenance
      for several days may be important for increasing blood flow and angiogenesis.

PMID- 22969256
TI  - Elevated insulin and insulin resistance are associated with the advanced
      pathological stage of prostate cancer in Korean population.
AB  - The study was designed to investigate the effect of serum glucose, insulin and
      insulin resistance on the risk of prostate cancer (CaP) and on the
      clinicopathological characteristics in Korean men. Subjects were retrospectively
      recruited from 166 CaP patients underwent radical prostatectomy and 166 age
      matched benign prostatic hyperplasia (BPH) patients. The serum was taken on the
      morning of the day of operation and insulin resistance was assessed by
      homeostasis model assessment insulin resistance index (HOMA-IR). Men in highest
      tertile of insulin was associated with 55% reduced odds of CaP than those with
      the lowest tertile (OR = 0.45, 95% CI = 0.23-0.89, P = 0.022). The patients in
      highest tertile of insulin had a more than 5.6 fold risk of locally advanced
      stage than those in the lowest tertile (OR = 5.62, 95% CI = 1.88-16.83, P =
      0.002). Moreover, the patients in the highest tertile HOMA-IR group was
      associated with an increased risk of locally advanced stage than the lowest
      tertile group (OR = 3.10, 95% CI = 1.07-8.99, P = 0.037). These results suggest
      that elevated insulin and insulin resistance are associated with the advanced
      pathological stage of prostate cancer in Korean patients.

PMID- 22969257
TI  - Antihypertensive treatment of acute intracerebral hemorrhage by intravenous
      nicardipine hydrochloride: prospective multi-center study.
AB  - The authors performed a multicenter prospective study to evaluate the feasibility
      and safety of intravenous nicardipine hydrochloride for acute hypertension in
      patients with intracerebral hemorrhage (ICH). This study included 88 patients
      (mean age: 58.3 yr, range 26-87 yr) with ICH and acute hypertension in 5 medical
      centers between August 2008 and November 2010, who were treated using intravenous
      nicardipine. Administration of nicardipine resulted in a decrease from mean
      systolic blood pressure (BP) (175.4 +/- 33.7 mmHg) and diastolic BP (100.8 +/- 22
      mmHg) at admission to mean systolic BP (127.4 +/- 16.7 mmHg) and diastolic BP
      (67.2 +/- 12.9 mmHg) in 6 hr after infusion (P < 0.001, mixed-effect linear
      models). Among patients who underwent follow-up by computed tomography, hematoma
      expansion at 24 hr (more than 33% increase in hematoma size at 24 hr) was
      observed in 3 (3.4%) of 88 patients. Neurological deterioration (defined as a
      decrease in initial Glasgow coma scale >= 2) was observed in 2 (2.2%) of 88
      patients during the treatment. Aggressive nicardipine treatment of acute
      hypertension in patients with ICH can be safe and effective with a low rate of
      neurological deterioration and hematoma expansion.

PMID- 22969258
TI  - Prevalence and distribution of human papillomavirus infection in Korean women as
      determined by restriction fragment mass polymorphism assay.
AB  - The development of a prophylactic vaccine that targets human papillomaviruses
      (HPV) 6, 11, 16, and 18 to prevent cervical cancer has increased interest in the
      ethnic and geographical distributions of HPV genotypes. We investigated HPV
      prevalence and type distribution by restriction fragment mass polymorphism (RFMP)
      testing a total of 60,775 specimens (aged 18-79 yr, median 44) taken from liquid
      based cytology. Overall HPV positive rate of total patients was 34.2%. Among the
      positive patients, 87.7% was single type infections, and 12.3% was multiple HPV
      types. HPV-16 was the most prevalent genotype observed in 2,307 (26.0%), followed
      by type 52 in 2,269 (25.5%), type 58 in 1,090 (12.3%), type 18 in 633 (7.1%),
      type 56 in 436 (4.9%). The pattern of high risk-HPV positive rate according to
      age showed U-shape with a peak in HPV prevalence among women less than 30 yr of
      age, and a second peak among the older females aged 70 to 79 yr. The leading four
      high-risk HPV genotypes were HPV-16, HPV-52, HPV-58, and HPV-18 in descending
      order. In conclusion, this study provides the most representative prevalence and
      type-specific distribution of HPV among Korean women, and demonstrates that the
      epidemiology of HPV infection is different from that of other regions of the
      world.

PMID- 22969259
TI  - Salivary bisphenol-A levels due to dental sealant/resin: a case-control study in
      Korean children.
AB  - Dental sealants and composite filling materials containing bisphenol-A (BPA)
      derivatives are increasingly used in children. The aim of this study was to
      evaluate the association between salivary BPA and the number of tooth surfaces
      filled with dental sealant, and to determine a cutoff BPA level. Salivary BPA
      concentration and the number of tooth surfaces filled with dental sealant/resin
      were determined in 124 age and gender matched children: 62 controls had no dental
      sealant/resin on their tooth surfaces and 62 cases had more than 4 tooth surfaces
      with dental sealant/resin. Analysis of covariance (ANCOVA) and conditional
      logistic regression were performed after controlling for age, gender, salivary
      flow rate, salivary buffer capacity, frequency of snacking, and frequency of
      tooth brushing. Salivary BPA levels were 0.002 to 8.305 ug/L. The BPA level of
      control (0.40 ug/L) was significantly lower than that of case (0.92 ug/L) after
      controlling for confounders (P = 0.026). Although the 90th BPA percentile had an
      adjusted OR of 4.58 (95% CI 1.04-20.26, P = 0.045), the significance disappeared
      in the conditional logistic model. There may be a relationship between salivary
      BPA level and dental sealant/resin.

PMID- 22969260
TI  - Meningitis by Toxocara canis after ingestion of raw ostrich liver.
AB  - Recently reports on toxocariasis are increasing by serodiagnosis in Korea. A
      previously healthy 17-yr-old boy complained of headache, fever, dyspnea, and
      anorexia. He showed symptoms and signs of eosinophilic meningitis with
      involvement of the lungs and liver. Specific IgG antibody to Toxocara canis
      larval antigen was positive in serum and cerebrospinal fluid by ELISA. He took
      raw ostrich liver with his parents 4 weeks before the symptom onset. His parents
      were seropositive for T. canis antigen but had no symptoms or signs suggesting
      toxocariasis. This is the first report of toxocariasis in a family due to
      ingestion of raw ostrich liver in Korea.

PMID- 22969261
TI  - A case of transient central diabetes insipidus after aorto-coronary bypass
      operation.
AB  - Diabetes insipidus (DI) is characterized by excessive urination and thirst. This
      disease results from inadequate output of antidiuretic hormone (ADH) from the
      pituitary gland or the absence of the normal response to ADH in the kidney. We
      present a case of transient central DI in a patient who underwent a
      cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr
      old male underwent a CABG operation. An hour after the operation, the patient
      developed polyuria and was diagnosed with central DI. The patient responded to
      desmopressin and completely recovered five days after surgery. It is probable
      that transient cerebral ischemia resulted in the dysfunction of osmotic receptors
      in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also
      possible that cardiac standstill altered the left atrial non-osmotic receptor
      function and suppressed ADH release. Therefore, we suggest that central DI is a
      possible cause of polyuria after CPB.

PMID- 22969262
TI  - Recurrent plastic bronchitis in a child with 2009 influenza A (H1N1) and
      influenza B virus infection.
AB  - Plastic bronchitis is an uncommon disorder characterized by the formation of
      bronchial casts. It is associated with congenital heart disease or pulmonary
      disease. In children with underlying conditions such as allergy or asthma,
      influenza can cause severe plastic bronchitis resulting in respiratory failure. A
      review of the literature showed nine cases of plastic bronchitis with H1N1
      including this case. We report a case of a child with recurrent plastic
      bronchitis with eosinophilic cast associated with influenza B infection, who had
      recovered from plastic bronchitis associated with an influenza A (H1N1) virus
      infection 5 months previously. To the best of our knowledge, this is the first
      case of recurrent plastic bronchitis related to influenza viral infection. If
      patients with influenza virus infection manifest acute respiratory distress with
      total lung atelectasis, clinicians should consider plastic bronchitis and early
      bronchoscopy should be intervened. In addition, management for underlying disease
      may prevent from recurrence of plastic bronchitis.

PMID- 22969263
TI  - Ceftiaxone-induced neurotoxicity: case report, pharmacokinetic considerations,
      and literature review.
AB  - Ceftriaxone is widely used in patients for the treatment of serious gram-negative
      infections. Ceftriaxone can induce some potential side effects, including
      neurotoxicity, however, nonconvulsive status epilepticus has rarely been
      reported. We report a case of acute reversible neurotoxicity associated with
      ceftriaxone. A 65-yr-old woman with chronic kidney disease developed altered
      consciousness during ceftriaxone treatment for urinary tract infection. The
      electroencephalogram demonstrated continuous bursts of generalized, high-voltage,
      1 to 2 Hz sharp wave activity. Neurologic symptoms disappeared following
      withdrawal of ceftriaxone. The possibility of ceftriaxone-induced neurotoxicity
      should be considered in patients developing neurological impairment during
      ceftriaxone use, and the discontinuation of the drug could lead to complete
      neurological improvement.

PMID- 22969264
TI  - Familial hemiplegic migraine with prolonged coma and cerebellar atrophy: CACNA1A
      T666M mutation in a Korean family.
AB  - We report the first Korean patient with familial hemiplegic migraine type 1, with
      clinical and multimodal imaging findings. A 43-yr-old man was admitted for right
      hemianopia and aphasia, followed by coma. MRI showed only cerebellar atrophy. CT
      angiography showed mild vasodilation of intracranial blood vessels and increased
      vascularity in the left hemisphere and perfusion-weighted imaging showed elevated
      cerebral blood flow. Gene analysis of the patient and his mother led to the
      identification of a heterozygous point mutation (1997C->T, T666M) in exon 16 of
      the CACNA1A gene. Familial hemiplegic migraine should be considered in patients
      with episodic neurological dysfunction with cerebellar atrophy.

PMID- 22969266
TI  - Oncogenic microRNA 17-92 cluster is regulated by epithelial cell adhesion
      molecule and could be a potential therapeutic target in retinoblastoma.
AB  - PURPOSE: Several miRNAs have been reported as candidate oncogenes and tumor
      suppressors, which are involved in the pathways specifically altered during
      tumorigenesis or metastasis. The miR 17-92 cluster located in 13q31 locus might
      contribute to retinoblastoma (RB) oncogenesis as 13q31 is amplified often in RB.
      We attempted to identify the factors involved in the regulation of miR 17-92
      cluster in RB. METHODS: Real-time quantitative reverse transcriptase PCR was
      performed to study the expression of the miR 17-92 cluster in primary RB tumors
      and in Y79 cells after epithelial cell adhesion molecule (EpCAM) silencing. EpCAM
      was silenced using siRNA and confirmed by western blotting. The Y79 cells were
      transfected with individual and mixed antagomirs and studied the cell viability
      by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,
      invasion by matrigel analysis and caspase-3 expression by flow cytometry.
      RESULTS: The relative expression of miR 17-92 cluster, compared to that of a
      normal retina, ranged from 25 to 220 fold (p<0.0001), miR-18 being highly
      expressed in RB. Post EpCAM silencing resulted in a significant decrease (p<0.01)
      in the expression of the miR 17-92 cluster by 4 to eightfold in Y79 cells. Y79
      cells transfected with an antagomirs mix (all 5 miRNAs) showed decreased cell
      viability (p<0.001) and cell invasion (p<0.001). Similarly, Y79 cells treated
      with antagomirs mix showed increased expression of caspase-3 (p<0.001), which
      confirms the anti-proliferative effect of antagomirs. CONCLUSIONS: This study has
      showed varied expression of the miR17-92 cluster in primary RB tumors. EpCAM
      influences miR 17-92 cluster expression in retinoblastoma. In addition, we showed
      that the miR 17-92 cluster plays a role in RB cell proliferation and invasion.
      Therefore, targeting the miRNA 17-92 cluster may be beneficial for controlling
      Y79/RB cell proliferation and invasion.

PMID- 22969268
TI  - Catalytic Activity of Biomorphic alpha-MoO(3) in the Degradation of Methyl Violet
      Dye.
AB  - A network of fibers comprising orthorhombic molybdenum trioxide (alpha-MoO(3))
      crystals were synthesized using paper as template via a biomorphic approach. The
      template was completely removed by annealing the sample at 600 degrees C for 5
      min. Monoclinic MoO(3) was formed and consequently converted into orthorhombic
      alpha-MoO(3) after prolonged annealing. Three milligrams of the biomorphic alpha
      MoO(3) could degrade up to 90% of a methyl violet aqueous solution with a
      concentration of 20 mg/L under normal visible light. The size of the alpha-MoO(3)
      grains and the porosity of the biomorphic sample affected catalytic performance.

PMID- 22969269
TI  - Volatile Organic Compounds in Ambient Air at Four Residential Locations in Seoul,
      Korea.
AB  - To investigate the environmental behavior of volatile organic compounds (VOCs) in
      urban areas, their concentrations were measured at four urban monitoring sites
      (namely, N, S, E, and W) in Seoul, Korea (February to December 2009). A total of
      27 compounds were quantified that consist of four chemical groups: aromatic (AR),
      halogenated aromatic, halogenated paraffin, and halogenated olefin. Results were
      evaluated by focusing on these four functional groups just mentioned and their
      summation term as total VOC (TVOC) along with several individual species (mainly
      AR species, that is, benzene, toluene, ethylbenzene, and xylene). The highest
      concentration of chemical groups was found from AR (71.1+/-42.1 ppbC), while that
      for individual species confirmed the dominance of toluene (7.48+/-3.88 ppb). The
      analysis of spatial distribution indicated that high TVOC levels were recorded at
      sites N and W, while it was not so significant such as S and E in terms of TVOC
      budget. Seasonal variation of these VOCs was characterized by the peak values in
      December to reflect the combined effects of pronounced source activities and
      meteorological conditions. Analysis of spatial variations in VOC levels between
      the four urban sites indicated that their distributions are tightly affected by
      local source processes in each area.

PMID- 22969270
TI  - Enhancement of lipid extraction from marine microalga, Scenedesmus associated
      with high-pressure homogenization process.
AB  - Marine microalga, Scenedesmus sp., which is known to be suitable for biodiesel
      production because of its high lipid content, was subjected to the conventional
      Folch method of lipid extraction combined with high-pressure homogenization
      pretreatment process at 1200 psi and 35 degrees C. Algal lipid yield was about
      24.9% through this process, whereas only 19.8% lipid can be obtained by following
      a conventional lipid extraction procedure using the solvent, chloroform:methanol
      (2:1, v/v). Present approach requires 30 min process time and a moderate working
      temperature of 35 degrees C as compared to the conventional extraction method
      which usually requires >5 hrs and 65 degrees C temperature. It was found that
      this combined extraction process followed second-order reaction kinetics, which
      means most of the cellular lipids were extracted during initial periods of
      extraction, mostly within 30 min. In contrast, during the conventional extraction
      process, the cellular lipids were slowly and continuously extracted for >5 hrs by
      following first-order kinetics. Confocal and scanning electron microscopy
      revealed altered texture of algal biomass pretreated with high-pressure
      homogenization. These results clearly demonstrate that the Folch method coupled
      with high-pressure homogenization pretreatment can easily destruct the rigid cell
      walls of microalgae and release the intact lipids, with minimized extraction time
      and temperature, both of which are essential for maintaining good quality of the
      lipids for biodiesel production.

PMID- 22969271
TI  - Animal models of human pathology 2012.

PMID- 22969272
TI  - Anatomy of biometric passports.
AB  - Travelling is becoming available for more and more people. Millions of people are
      on a way every day. That is why a better control over global human transfer and a
      more reliable identity check is desired. A recent trend in a field of personal
      identification documents is to use RFID (Radio Frequency Identification)
      technology and biometrics, especially (but not only) in passports. This paper
      provides an insight into the electronic passports (also called e-passport or
      ePassport) implementation chosen in the Czech Republic. Such a summary is needed
      for further studies of biometric passports implementation security and biometric
      passports analysis. A separate description of the Czech solution is a
      prerequisite for a planned analysis, because of the uniqueness of each
      implementation. (Each country can choose the implementation details within a
      range specified by the ICAO (International Civil Aviation Organisation);
      moreover, specific security mechanisms are optional and can be omitted).

PMID- 22969267
TI  - Plasma levels of complement proteins from the alternative pathway in patients
      with age-related macular degeneration are independent of Complement Factor H
      Tyr402His polymorphism.
AB  - PURPOSE: To investigate the influence of the Factor H (CFH) Tyr402His
      polymorphism on the plasma levels of the alternative pathway proteins CFH, C3,
      Factor B (FB), Factor D (FD), and Factor I (FI) and the inflammatory marker C
      reactive protein (CRP) in 119 patients with age-related macular degeneration
      (AMD) and 152 unrelated control individuals. METHODS: Patients with AMD and the
      control group were separated according to CFH polymorphism, age, and gender.
      Plasma complement proteins and CRP concentrations were determined with enzyme
      linked immunosorbent assay, immunodiffusion, or nephelometry. RESULTS:
      Significant differences in the concentrations of FD and FI were observed between
      the patients with AMD and the control individuals. We observed significantly
      reduced FD plasma levels in patients with AMD. We also identified a significant
      decrease in CFH plasma levels in female patients with AMD in relation to female
      controls. Plasma FI levels were significantly increased in patients with AMD
      compared to the control group. Regarding gender, a significant increase in FI
      plasma levels was observed in male patients. Finally, we found no significant
      correlation between the CFH Tyr(402)His polymorphism and the CFH, C3, FB, FD, FI,
      and CRP plasma levels. CONCLUSIONS: Patients with AMD present altered levels of
      FD and FI in a manner independent of this CFH polymorphism, and gender apparently
      contributes to the plasma levels of these two proteins in patients with AMD and
      control individuals.

PMID- 22969273
TI  - A privacy-preserved analytical method for ehealth database with minimized
      information loss.
AB  - Digitizing medical information is an emerging trend that employs information and
      communication technology (ICT) to manage health records, diagnostic reports, and
      other medical data more effectively, in order to improve the overall quality of
      medical services. However, medical information is highly confidential and
      involves private information, even legitimate access to data raises privacy
      concerns. Medical records provide health information on an as-needed basis for
      diagnosis and treatment, and the information is also important for medical
      research and other health management applications. Traditional privacy risk
      management systems have focused on reducing reidentification risk, and they do
      not consider information loss. In addition, such systems cannot identify and
      isolate data that carries high risk of privacy violations. This paper proposes
      the Hiatus Tailor (HT) system, which ensures low re-identification risk for
      medical records, while providing more authenticated information to database users
      and identifying high-risk data in the database for better system management. The
      experimental results demonstrate that the HT system achieves much lower
      information loss than traditional risk management methods, with the same risk of
      re-identification.

PMID- 22969274
TI  - Differential control of growth, apoptotic activity, and gene expression in human
      breast cancer cells by extracts derived from medicinal herbs Zingiber officinale.
AB  - The present study aimed to examine the antiproliferative potentiality of an
      extract derived from the medicinal plant ginger (Zingiber officinale) on growth
      of breast cancer cells. Ginger treatment suppressed the proliferation and colony
      formation in breast cancer cell lines, MCF-7 and MDA-MB-231. Meanwhile, it did
      not significantly affect viability of nontumorigenic normal mammary epithelial
      cell line (MCF-10A). Treatment of MCF-7 and MDA-MB-231 with ginger resulted in
      sequences of events marked by apoptosis, accompanied by loss of cell viability,
      chromatin condensation, DNA fragmentation, activation of caspase 3, and cleavage
      of poly(ADP-ribose) polymerase. At the molecular level, the apoptotic cell death
      mediated by ginger could be attributed in part to upregulation of Bax and
      downregulation of Bcl-2 proteins. Ginger treatment downregulated expression of
      prosurvival genes, such as NF-kappaB, Bcl-X, Mcl-1, and Survivin, and cell cycle
      regulating proteins, including cyclin D1 and cyclin-dependent kinase-4 (CDK-4).
      On the other hand, it increased expression of CDK inhibitor, p21. It also
      inhibited the expression of the two prominent molecular targets of cancer, c-Myc
      and the human telomerase reverse transcriptase (hTERT). These findings suggested
      that the ginger may be a promising candidate for the treatment of breast
      carcinomas.

PMID- 22969275
TI  - An in vivo rabbit model for the evaluation of antimicrobial peripherally inserted
      central catheter to reduce microbial migration and colonization as compared to an
      uncoated PICC.
AB  - Infection is the leading complication associated with intravascular devices, and
      these infections develop when a catheter becomes colonized by microorganisms. To
      combat this issue, medical device manufacturers seek to provide healthcare
      facilities with antimicrobial medical devices to prevent or reduce the
      colonization. In order to adequately evaluate these devices, an in vivo model is
      required to accurately assess the performance of the antimicrobial devices in a
      clinical setting. The model presented herein was designed to provide a simulation
      of the subcutaneous tunnel environment to evaluate the ability of an
      antimicrobial peripherally inserted central catheter (PICC), coated with
      chlorhexidine based technology, to reduce microbial migration and colonization
      compared to an uncoated PICC. Three samples of control, uncoated PICCs and three
      samples of coated PICCs were surgically tunneled into the backs of female New
      Zealand White rabbits. The insertion sites were then challenged with
      Staphylococcus aureus at the time of implantation. Animals were evaluated out to
      thirty days and sacrificed. Complete en bloc dissection and evaluation of the
      catheter and surrounding tissue demonstrated that the chlorhexidine coated
      catheter was able to significantly reduce microbial colonization and prevent
      microbial migration as compared to the standard, un-treated catheter.

PMID- 22969276
TI  - Effects of BAK-free travoprost treatment for 3 years in patients with normal
      tension glaucoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of benzalkonium
      (BAK)-free travoprost monotherapy administered for 3 years on intraocular
      pressure and visual field performance. METHODS: The intraocular pressure of 76
      patients with normal tension glaucoma was monitored every 1-3 months. A Humphrey
      visual field test was performed every 6 months after treatment and compared with
      the results before treatment. Visual field performance was also evaluated by
      trend and event analysis. RESULTS: Thirty cases discontinued within 3 years. Mean
      intraocular pressure after 3 years of travoprost treatment (14.1 +/- 2.4 mmHg)
      was significantly lower than that before treatment (16.8 +/- 2.6 mmHg, P <
      0.0001). There was no change in the mean deviation and pattern standard deviation
      as measured by Humphrey visual field test after 3 years of treatment compared
      with before treatment. Visual field performance was worse in one patient (2.8%)
      by trend analysis and five patients (13.9%) by event analysis. Treatment was
      discontinued in six cases (7.9%) due to the appearance of adverse reactions.
      CONCLUSION: BAK-free travoprost monotherapy was effective in reducing intraocular
      pressure for at least 3 years; however, visual field performance worsened in 2.8%
      13.9% of patients with normal tension glaucoma.

PMID- 22969277
TI  - Commercially available rigid gas-permeable contact lens for protecting the cornea
      from drying during vitrectomy with a wide viewing system.
AB  - PURPOSE: We evaluated the usefulness of commercially available materials for
      protecting the cornea from drying during vitrectomy with a wide-angle viewing
      system. METHODS: THREE VITREORETINAL SURGEONS EVALUATED FUNDUS VISIBILITY DURING
      VITRECTOMY ON THE IMAGES OF FIVE STUDY MATERIALS USED ON THE CORNEA: balanced
      saline solution, a viscoelastic agent, a vitrectomy contact lens, a rigid gas
      permeable (RGP) contact lens, and a soft contact lens. Fundus visibility was
      graded using the following scale: grade 1, unclear; grade 2, slightly unclear;
      grade 3, clear; and grade 4, very clear. RESULTS: RESPECTIVE SCORES FOR EACH
      MATERIAL USED DURING CORE VITRECTOMY AND MEMBRANE REMOVAL WERE: balanced saline
      solution, 3.3/3.3; viscoelastic agent, 3.8/3.3; vitrectomy contact lens, 3.3/4.0;
      RGP contact lens, 4.0/3.9; soft contact lens, 1.1/not applicable. CONCLUSION: The
      RGP contact lens provided visibility similar to or clearer than that obtained
      with other methods. Because of its ease of use and lower cost, use of the RGP
      contact lens is ideal during vitrectomy performed with a wide-angle viewing
      system.

PMID- 22969278
TI  - Retinopathy associated with interferon therapy in patients with hepatitis C
      virus.
AB  - PURPOSE: To evaluate retinopathy associated with interferon therapy in patients
      with chronic hepatitis C. METHODS: One hundred patients with chronic hepatitis C
      undergoing interferon therapy were examined for the presence of cotton wool
      spots, retinal hemorrhages, cystoid macular edema, capillary non-perfusion, and
      arteriolar occlusion. Complete ophthalmological examination including indirect
      ophthalmoscopic fundus examination was carried out for all patients and colored
      fundus photography and fluorescein angiography were carried out for the patients
      with positive fundus findings. The follow-up period was 9 months. RESULTS:
      Sixteen percent of patients developed retinopathy in the form of cotton wool
      spots, retinal hemorrhages, cystoid macular edema, and capillary non-perfusion.
      CONCLUSION: Interferon therapy can lead to retinopathy which is mostly reversible
      and dose related. Periodic fundoscopic examinations help in early detection and
      prevent progression to permanent visual loss.

PMID- 22969279
TI  - Intraoperative intravitreal triamcinolone decreases macular edema after
      vitrectomy with phacoemulsification.
AB  - BACKGROUND: The purpose of this study was to evaluate the incidence and amount of
      macular edema by optical coherence tomography (OCT) after combined small gauge
      sutureless vitrectomy with phacoemulsification and intravitreal triamcinolone.
      METHODS: This retrospective case series included 194 consecutive eyes undergoing
      nonemergent vitrectomy with phacoemulsification and intravitreal triamcinolone.
      Ninety-one eyes had preoperative and postoperative OCT available and were
      included in the analysis. The eyes were evaluated for retinal thickness with
      preoperative and postoperative OCT, and for preoperative and postoperative best
      corrected visual acuity. The main outcome measures were retinal thickness, OCT
      appearance, and best-corrected visual acuity. RESULTS: The incidence of macular
      edema in all eyes preoperatively was 64.8% and postoperatively was 50.5%. Mean
      central subfield and center point thickness in eyes with macular edema
      preoperatively were 361 MUm and 349 MUm, respectively, and postoperatively were
      315 MUm and 304 MUm, respectively. In eyes without preoperative macular edema,
      mean preoperative central subfield and center point thickness were, respectively,
      210 MUm and 181 MUm versus 220 MUm and 192 MUm postoperatively. Best corrected
      visual acuity improved from 20/190 preoperatively to 20/150 at postoperative
      month 1 and 20/110 at month 6. Postoperative intraocular pressure >= 25 mmHg was
      observed in 7.7% of eyes, none of which required surgical intervention for
      steroid-induced glaucoma. CONCLUSION: Use of intravitreal triamcinolone with
      combined vitrectomy and phacoemulsification may play an important role in
      modulating postoperative macular edema. Adverse pressure rise is infrequent and
      usually limited.

PMID- 22969280
TI  - Boston type I keratoprosthesis-donor cornea interface evaluated by high
      definition spectral-domain anterior segment optical coherence tomography.
AB  - BACKGROUND: The purpose of this study was to assess whether the resolution
      offered by two different, recently commercially available high-resolution,
      spectral-domain anterior segment optical coherence tomography (AS-OCT)
      instruments allows for detailed anatomic characterization of the critical device
      donor cornea interface in eyes implanted with the Boston type I permanent
      keratoprosthesis. METHODS: Eighteen eyes of 17 patients implanted with the Boston
      type I keratoprosthesis were included in this retrospective case series. All eyes
      were quantitatively evaluated using the Cirrus HD-OCT while a subset (five eyes)
      was also qualitatively imaged using the Spectralis Anterior Segment Module.
      Images from these instruments were analyzed for evidence of epithelial migration
      onto the anterior surface of the keratoprosthesis front plate, and presence of a
      vertical gap between the posterior surface of the front plate and the underlying
      carrier donor corneal tissue. Quantitative data was obtained utilizing the
      caliper function on the Cirrus HD-OCT. RESULTS: The mean duration between AS-OCT
      imaging and keratoprosthesis placement was 29 months. As assessed by the Cirrus
      HD-OCT, 83% of eyes exhibited epithelial migration over the edge of the front
      plate. Fifty-six percent of the keratoprosthesis devices displayed good
      apposition of the device with the carrier corneal donor tissue. When a vertical
      gap was present (44% of eyes), the mean gap was 40 (range 8-104) microns. The
      Spectralis Anterior Segment Module also displayed sufficient resolution to allow
      for similar characterization of the device-donor cornea interface. CONCLUSION:
      Spectral-domain AS-OCT permits high resolution imaging of the keratoprosthesis
      device-donor cornea interface. Both the Cirrus HD-OCT and the Spectralis Anterior
      Segment module allowed for visualization of epithelial coverage of the device
      donor cornea interface, as well as identification of physical gaps. These imaging
      modalities, by yielding information in regard to integration of the
      keratoprosthesis with surrounding corneal tissue, may help identify those at risk
      for keratoprosthesis-related complications, such as extrusion and
      endophthalmitis, and hence guide clinical management.

PMID- 22969281
TI  - Choroidal excavation with polypoidal choroidal vasculopathy: a case report.
AB  - PURPOSE: This is a report of a case of choroidal excavation accompanied by
      polypoidal choroidal vasculopathy (PCV) and retinal pigment epithelium detachment
      (PED). METHODS: A 57-year-old Japanese woman who had begun complaining of
      metamorphopsia in her left eye 7 months earlier underwent spectral-domain optical
      coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine
      green angiography (IA), as well as a routine ophthalmological examination.
      RESULTS: The patient's intraocular pressure, visual acuity, and visual field were
      within normal range. Ophthalmoscopy revealed a serous macular detachment, soft
      drusen, exudates, and a reddish-orange elevated lesion in the macula of the left
      eye. The right eye was normal. SD-OCT revealed two lesions in the left eye. One
      was a PED accompanied by a notch sign, and the other was a choroidal excavation.
      Additionally, FA revealed a window defect in the PED, and IA showed typical PCV.
      Three monthly injections of antivascular endothelial growth factor preserved
      visual acuity, but failed to have any visible effect on the lesion during the 6
      month follow up period. CONCLUSIONS: This is the first report of choroidal
      excavation accompanied by PED and PCV. The data suggest that choroidal excavation
      may be associated with various changes that have not been previously reported.
      Careful observation of such cases may therefore be necessary.

PMID- 22969283
TI  - Angiographic results of retinal-retinal anastomosis and retinal-choroidal
      anastomosis after treatments in eyes with retinal angiomatous proliferation.
AB  - BACKGROUND: The purpose of this study was to evaluate the angiographic results of
      retinal-retinal anastomosis (RRA) and retinal-choroidal anastomosis (RCA) for
      eyes with retinal angiomatous proliferation (RAP) after treatment with
      intravitreal bevacizumab injections as monotherapy or intravitreal bevacizumab
      combined with photodynamic therapy. METHODS: In this interventional, consecutive
      case series, we retrospectively reviewed five naive eyes from four patients (mean
      age 80 years) treated with three consecutive monthly intravitreal bevacizumab
      (1.25 mg/0.05 mL) injections as initial treatment, and followed up for at least 3
      months. In cases with over 3 months of follow-up and having recurrence of RAP or
      leakage by fluorescein angiography, retreatment was performed with a single
      intravitreal bevacizumab injection and photodynamic therapy. RESULTS: Indocyanine
      green angiography showed RRA in three eyes with subretinal neovascularization and
      RCA in two eyes with choroidal neovascularization at baseline. At 3 months after
      baseline (month 3), neither the RRA nor RCA was occluded in any eye on
      indocyanine green angiography. Retreatment with intravitreal bevacizumab plus
      photodynamic therapy was performed in three eyes at months 3 (persistent leakage
      on fluorescein angiography), 6, and 7 (recurrence of RAP lesion), which achieved
      obvious occlusion of the RRA and RCA. Mean best-corrected visual acuity improved
      from 0.13 to 0.21 at month 3 (P = 0.066). No complications or systemic adverse
      events were noted. CONCLUSION: Although intravitreal bevacizumab for RAP was
      effective in improving visual acuity during short-term follow-up, intravitreal
      bevacizumab could not achieve complete occlusion of RRA and RCA, which could lead
      to recurrence of a RAP lesion and exudation. Retreatment with intravitreal
      bevacizumab plus photodynamic therapy ultimately achieved complete occlusion of
      the RRA and RCA.

PMID- 22969282
TI  - Thrombophilia and retinal vascular occlusion.
AB  - PURPOSE: The purpose of this research was to assess associations of thrombophilia
      with central retinal vein occlusion (CRVO), central retinal artery occlusion
      (CRAO), and amaurosis fugax (AF); to evaluate outcomes of normalizing high
      homocysteine; and to study CRVO, CRAO, and AF developing in estrogens/estrogen
      agonists in women subsequently shown to have thrombophilia. METHODS: Measures of
      thrombophilia-hypofibrinolysis were obtained in 132 CRVO cases, 15 CRAO cases,
      and 17 AF cases. Cases were compared to 105 healthy control subjects who did not
      differ by race or sex and were free of any ophthalmologic disorders. All
      cardiovascular disease (CVD) risk factors were compared to healthy general
      populations. MAIN OUTCOME MEASURES: The main outcome measure of this study was
      thrombophilia. RESULTS: CRVO cases were more likely than controls to have high
      homocysteine (odds ratio [OR] 8.64, 95% confidence intervals [CI]: 1.96-38), high
      anticardiolipin immunoglobulin M (IgM; OR 6.26, 95% CI: 1.4-28.2), and high
      Factor VIII (OR 2.47, 95% CI: 1.31-7.9). CRAO-AF cases were more likely than
      controls to have high homocysteine (OR 14, 95% CI: 2.7-71.6) or the lupus
      anticoagulant (OR 4.1, 95% CI: 1.3-13.2). In four of 77 women with CRVO (two
      found to have high homocysteine, two with inherited high Factor XI), CRVO
      occurred after starting estrogen-progestins, estrogen-testosterone, or estrogen
      agonists. In one of eight women with CRAO found to have high anticardiolipin
      antibody IgG, CRAO occurred after starting conjugated estrogens, and AF occurred
      after starting conjugated estrogens in one of eleven women with AF (inherited
      protein S deficiency). Therapy for medians of 21 months (CRVO) and 6 months (CRAO
      AF) was 5 mg folic acid, 100 mg B6, and 2000 mcg/day B12 normalized homocysteine
      in 13 of 16 (81%) CRVO cases and all five CRAO-AF cases with pretreatment
      hyperhomocysteinemia. The CRVO cases had an excess of hypertension; CRAO-AF cases
      had an excess of type 2 diabetes and hypertension. CONCLUSION: Treatable
      thrombophilia, hyperhomocysteinemia in particular, is more common in RVO cases
      than in normal controls. RVO occurs after estrogens or estrogen agonists were
      administered in women subsequently shown to have thrombophilia.

PMID- 22969284
TI  - Four cases of endophthalmitis after 25-gauge pars plana vitrectomy.
AB  - We report our recent experience with four cases of endophthalmitis (one male,
      three females) after 25-gauge pars plana vitrectomy (PPV). One was a case of
      persistent cystoid macular edema caused by branch retinal vein occlusion, whereas
      the remaining three were cases of epiretinal membrane. Preoperative antibiotics
      before the first PPV procedure were not administered in three of the four cases.
      Endophthalmitis occurred 2-4 days after the first procedure in all cases, for
      which ceftazidime 2.0 mg/0.1 mL and vancomycin 1.0 mg/0.1 mL were injected into
      the vitreous cavity. This was followed by emergent 20-gauge PPV and intraocular
      lens removal using an infusion fluid containing ceftazidime and vancomycin. After
      the second PPV procedure, progress was good in three cases while retinal
      detachment occurred in the remaining case one month after surgery; this case
      required a third PPV procedure. Final best-corrected visual acuity ranged from
      20/100 to 20/25 for the four cases. Bacterial cultures were negative after the
      second PPV procedure in all cases. In conclusion, postoperative endophthalmitis
      occurred in four of 502 cases (0.80%) that underwent 25-gauge PPV at our
      hospital. It is important to minimize the incidence of endophthalmitis after 25
      gauge PPV.

PMID- 22969285
TI  - Exogenous group G Streptococcus endophthalmitis following intravitreal
      ranibizumab injection.
AB  - We report a case of group G Streptococcus endophthalmitis following an
      intravitreal ranibizumab injection for a choroidal neovascular membrane. Pars
      plana vitrectomy was applied for endophthalmitis and group G Streptococcus
      cultures were isolated in the vitreous samples taken from the patient. Twenty
      four hours following pars plana vitrectomy the patient underwent myocardial
      infarction and cardiac arrest. To our knowledge this is the first reported case
      of group G Streptococcus endophthalmitis following an intravitreal injection.

PMID- 22969286
TI  - Resolution of persistent corneal erosion after administration of topical
      rebamipide.
AB  - Rebamipide is an antiulcer agent used to treat gastric ulcer and gastritis.
      Biological effects of rebamipide include cytoprotection, wound healing, and anti
      inflammatory properties that are known to be universal for a variety of tissues
      in addition to gastrointestinal mucosa. The therapeutic effects of rebamipide eye
      drops are due to its ability to increase corneal and conjunctival mucin-like
      substances and improve corneal and conjunctival injury in vivo. In this paper, we
      report a case of Sjogren's syndrome with complete disappearance of corneal
      erosion after administration of rebamipide eye drops. This was observed even
      though corneal erosion had not improved for 6 months after punctal occlusion
      surgery. The patient was a 33-year-old female, diagnosed with Sjogren's syndrome
      by a salivary gland biopsy. The corneal and conjunctival surfaces were filled
      with dense erosions, which did not improve with topical drugs. Punctal plugs were
      applied several times; however, the plugs were repeatedly shed. All four puncta
      of both eyelids were surgically occluded, and both corneal and conjunctival
      erosion was clearly improved. However, the erosion in the inferior cornea of both
      eyes had not improved for 6 months after surgery. We used the newly approved
      topical rebamipide for treatment of this patient. The corneal erosion gradually
      improved and completely disappeared 4 weeks after administration of the drug. Dry
      eye sensation disappeared at the same time. Both membrane-associated mucin and
      secreted mucin in the ocular surface are thought to be essential for maintenance
      of the tear film. Induction of mucin from ocular surface epithelium could be an
      effective treatment in cases of dry eye caused by mucin deficiency. Through its
      various mechanisms, rebamipide improves ocular surface conditions. To our
      knowledge, this is the first clinical case report using rebamipide ophthalmic
      solution. This drug may provide a novel approach to treat drying diseases of the
      eye.

PMID- 22969287
TI  - Corneal reconstruction by stem cells and bioengineering.
AB  - Almost 300 million people are visually impaired worldwide due to various eye
      diseases such as cataracts, glaucoma, age-related macular degeneration, diabetic
      retinopathy, and corneal diseases. Notably, ten million people are blind because
      of severe ocular surface diseases and the majority of cases occur in developing
      countries. Blinding ocular surface diseases have, however, become treatable by
      grafting of surface layers, or by full-thickness transplantation of the cornea.
      As the demand for human corneal tissue for surface reconstruction and
      transplantation far exceeds the supply, methods are being developed to supplement
      tissue donation. Xenotransplantation of the cornea or cells from genetically
      modified pigs may become one of the solutions. Transplantation of limbal stem
      cells within tissue biopsies, to restore the transparency of the cornea is
      another remarkable method, which has shown its potential in several clinical
      studies. The combination of stem cell technology and engineering of biocompatible
      tissue equivalent, still at preclinical stage, has shown us how synthetic corneal
      tissue is able to guide cultured corneal stromal stem cells of human origin, to
      become native-like stroma, the most important layer of the cornea. These findings
      give hope for a large-quantity production of biomaterial for corneal
      reconstruction. As such, clinical ophthalmologists should become more familiar
      with the methods of laboratory science.

PMID- 22969288
TI  - A comparison of the NEIVFQ25 and GQL-15 questionnaires in Nigerian glaucoma
      patients.
AB  - AIM: To compare two vision-specific quality of life (QOL) instruments - the
      disease-specific 15-item Glaucoma Quality of Life questionnaire (GQL-15) and the
      nonglaucoma-specific 25-item National Eye Institute Visual Function Questionnaire
      (NEIVFQ25). METHODS: The QOL of 132 glaucoma patients being managed in Lagos
      University Teaching Hospital and an equal number of controls matched for age and
      sex was assessed using two vision-specific instruments: GQL-15 and the NEIVFQ25.
      The categorization of the severity of glaucoma into mild, moderate, and severe
      disease was determined using the degree of visual field loss. The Statistical
      Package for the Social Sciences (version 15; SPSS Inc, Chicago, IL) software
      program was used for analyzing the data obtained. Spearman's correlation
      coefficients were used to assess the correlation between the scores from the two
      questionnaires. RESULTS: Patients had the greatest difficulty with activities
      affected by glare and dark adaptation in the GQL-15. Driving and general vision
      were the factors most affected in the NEIVFQ25. The Spearman rho values showed
      strong correlations (rho > 0.55) between the NEIVFQ25 and GQL-15 QOL scores for
      the total number of participants (rho: -0.75), total number of cases (rho: 
      0.83), and the mild (rho: -0.76), moderate (rho: -0.75), and severe (rho: -0.84)
      cases. There was a moderate correlation (rho: -0.38) for QOL scores of controls.
      Cronbach's alpha was 0.94 for the GQL-15 and 0.93 for the NEIVFQ25, showing high
      internal consistency for both questionnaires. CONCLUSION: The GQL-15 and the
      NEIVFQ25 questionnaires showed high internal consistency, correlated strongly
      with each other, and were reliable in the assessment of glaucoma patients in this
      study.

PMID- 22969289
TI  - Visual and refractive outcomes after implantation of a fully diffractive trifocal
      lens.
AB  - BACKGROUND: The purpose of this study was to record the visual outcomes of
      patients treated by six surgeons after implantation of a trifocal lens. METHODS:
      The setting for this study comprised six ophthalmology units and eye clinics in
      Belgium and France, with a coordinating center in France, and data management and
      statistical analysis in France and Belgium. Ninety-four eyes from 47 patients
      were implanted with a trifocal FineVision((r)) intraocular lens by six surgeons.
      Monocular and binocular, uncorrected and best distance-corrected, and photopic
      and mesopic visual acuity was measured, as well as the defocus curve between +4 D
      and -4 D with best distance correction. RESULTS: Near and far monocular visual
      acuities were similar to the data published after bifocal intraocular lens
      implantation. Intermediate vision was improved, and was demonstrated by scores of
      near visual acuity as well as far visual acuity with defocus -1.5 D-add lens. Far
      vision is maintained in mesopic conditions. CONCLUSION: The trifocal intraocular
      lens provides good far, intermediate, and near visual acuity.

PMID- 22969290
TI  - Bilateral intraorbital abscesses with intracranial complications in a young
      Cameroonian girl: a case report.
AB  - BACKGROUND: Intraorbital abscess is a very severe infection with ophthalmologic
      and neurologic complications that are sometimes life-threatening. OBJECTIVE: To
      report the etiologic, clinical, radiologic, and prognostic features of one case
      of bilateral intraorbital abscesses with intracranial complications. CASE REPORT:
      A 15-year-old Cameroonian girl in a comatose state (11/15 on the Glasgow Coma
      Scale) with meningeal signs, right hemiplegia, right facial palsy, and bilateral
      exophthalmia was admitted for meningitis and cerebral abscess secondary to
      orbital cellulitis. A lumbar tap was carried out, no organisms were seen by Gram
      stain, and culture was negative due to previous antibiotic therapy. A computed
      tomography scan showed a left internal capsule infarct and a pansinus
      opacification. Bilateral superior orbitotomies were performed and the abscess
      evacuated. Microscopy and culture of surgical material were negative. The patient
      was discharged 4 weeks after hospital admission with a visual acuity of 0.1 in
      both eyes, aphasia, and right hemiplegia. Nine months later, there was complete
      visual recovery (visual acuity 1.0 in both eyes). Anterior and posterior segments
      were normal on slit-lamp examination. There was no aphasia, but right-sided
      hemiparesis persisted. CONCLUSION: The authors emphasize the need for prevention,
      early diagnosis, and adequate treatment of orbital cellulitis in order to avoid
      complications.

PMID- 22969291
TI  - Pharmacist-based Donepezil Outpatient Consultation Service to improve medication
      persistence.
AB  - AIM: Donepezil is widely used to delay the progression of cognitive dysfunction
      in patients with Alzheimer's disease (AD), but the efficacy of pharmacotherapy is
      often reduced by poor adherence to medication. In order to improve adherence by
      providing information about AD and the significance of pharmacotherapy, the
      Donepezil Outpatient Consultation Service (DOCS) was set up. The influence of
      this service on medication persistence was assessed in the present study.
      METHODS: Among outpatients starting donepezil therapy, we enrolled 59 patients
      between April 2008 and September 2010 before establishment of the DOCS (non-DOCS
      group) and 52 patients between October 2010 and March 2012 who attended the DOCS
      (DOCS group). Each patient's and their caregiver's understanding about the
      clinical features of AD and pharmacotherapy with donepezil were also assessed.
      Their understanding was compared before and after the DOCS, and the 1-year
      medication persistence rate and the reasons for discontinuation were also
      investigated. RESULTS: The 1-year medication persistence rate was significantly
      higher in the DOCS group than in the non-DOCS group (73.1% vs 49.2%, P = 0.008).
      We examined the association of medication persistence with age, sex, clinical
      dementia rating, living alone, and attending the DOCS. As a result, medication
      persistence was significantly higher in patients attending the DOCS. The main
      reasons for discontinuation of donepezil were transfer elsewhere (11) and
      gastrointestinal side effects (5) in the non-DOCS group, and transfer (9) and
      gastrointestinal side effects (3) in the DOCS group. The overall score for
      understanding was 2.5 +/- 1.7 before attending the DOCS and it increased
      significantly to 5.7 +/- 0.7 afterward (P < 0.001). CONCLUSION: The DOCS
      consultation provided by hospital pharmacists for AD patients and their
      caregivers improved understanding about the clinical features of dementia and
      provided pharmacological knowledge about antidementia drugs, leading to better
      adherence to pharmacotherapy that could maximize its effect.

PMID- 22969292
TI  - Medication adherence among hypertensive patients of primary health clinics in
      Malaysia.
AB  - PURPOSE: Poor adherence to prescribed medications is a major cause for treatment
      failure, particularly in chronic diseases such as hypertension. This study was
      conducted to assess adherence to medications in patients undergoing hypertensive
      treatment in the Primary Health Clinics of the Ministry of Health in Malaysia.
      Factors affecting adherence to medications were studied, and the effect of
      nonadherence to blood pressure control was assessed. PATIENTS AND METHODS: This
      was a cross-sectional study to assess adherence to medications by adult patients
      undergoing hypertensive treatment in primary care. Adherence was measured using a
      validated survey form for medication adherence consisting of seven questions. A
      retrospective medication record review was conducted to collect and confirm data
      on patients' demographics, diagnosis, treatments, and outcomes. RESULTS: Good
      adherence was observed in 53.4% of the 653 patients sampled. Female patients were
      found to be more likely to adhere to their medication regime, compared to their
      male counterparts (odds ratio 1.46 [95% confidence intervals [CI]: 1.05-2.04; P <
      0.05]). Patients in the ethnic Chinese were twice as likely (95% CI: 1.14-3.6; P
      < 0.05) to adhere, compared to those in the Indian ethnic group. An increase in
      the score for medicine knowledge was also found to increase the odds of
      adherence. On the other hand, increasing the number of drugs the patient was
      taking and the daily dose frequencies of the medications prescribed were found to
      negatively affect adherence. Blood pressure control was also found to be worse in
      noncompliers. CONCLUSION: The medication adherence rate was found to be low among
      primary care hypertensive patients. A poor adherence rate was found to negatively
      affect blood pressure control. Developing multidisciplinary intervention programs
      to address the factors identified is necessary to improve adherence and, in turn,
      to improve blood pressure control.

PMID- 22969294
TI  - Development of a men's Preference for Testosterone Replacement Therapy (P-TRT)
      instrument.
AB  - BACKGROUND: This study used a standard research approach to create a final
      conceptual model and the Preference for the Testosterone Replacement Therapy (P
      TRT) instrument. METHODS: A discussion guide was developed from a literature
      review and expert opinion to direct one-on-one interviews with participants who
      used testosterone replacement therapy and consented to participate in the study.
      Data from telephone interviews were transcribed for theme analysis using NVivo 9
      qualitative analysis software, analyzed descriptively from a saturation grid, and
      used to evaluate men's P-TRT. Data from cognitive debriefing for five
      participants were used to evaluate the final conceptual model and validate the
      initial P-TRT instrument. RESULTS: Item saturation and theme exhaustion was
      achieved by 58 male participants of mean age 55.0 +/- 10.0 (22-69) years who had
      used testosterone replacement therapy for a mean of 175.0 +/- 299.2 days. The
      conceptual model was developed from items and themes obtained from the
      participant interviews and saturation grid. Items comprising eight dimensions
      were used for instrument development, ie, ease of use, effect on libido, product
      characteristics, physiological impact, psychological impact, side effects,
      treatment experience, and preference. Results from the testosterone replacement
      therapy preference evaluation provide a detailed insight into why most men
      preferred a topical gel product over an injection or patch. CONCLUSION: Items and
      themes relating to use of testosterone replacement therapy were in concordance
      with the final conceptual model and 29-item P-TRT instrument. The standard
      research approach used in this study produced the P-TRT instrument, which is
      suitable for further psychometric development and use in clinical practice.

PMID- 22969293
TI  - Short-term clinical stability and lack of insight are associated with a negative
      attitude towards antipsychotic treatment at discharge in patients with
      schizophrenia and bipolar disorder.
AB  - PURPOSE: The primary aim of this study was to assess the range of attitudes
      towards antipsychotic treatment at hospital discharge in patients with
      schizophrenia and bipolar disorder. The secondary aim was to analyze the
      relationship between patients' attitudes and sociodemographic and clinical
      parameters. PATIENTS AND METHODS: A cross-sectional study with a sample of
      patients admitted due to acute exacerbation of schizophrenia or a manic episode
      was conducted. Attitude towards pharmacological treatment at discharge was
      assessed with the 10-item Drug Attitude Inventory (DAI-10). Logistic regression
      was used to determine significant variables associated with attitude to
      medication. RESULTS: Eighty-six patients were included in the study. The mean age
      was 43.1 years (standard deviation [SD] 12.1), and 55.8% were males. Twenty-six
      percent of the patients presented a negative attitude towards antipsychotic
      treatment (mean DAI-10 score of -4.7, SD 2.7). Most of them had a diagnosis of
      schizophrenia. Multivariate analysis showed that poor insight into illness and a
      greater number of previous acute episodes was significantly associated with a
      negative attitude towards medication at discharge (odds ratio 1.68 and 1.18,
      respectively). CONCLUSION: Insight and clinical stability prior to admission were
      related to patients' attitude towards antipsychotic treatment at hospital
      discharge among patients with schizophrenia and bipolar disorder. The
      identification of factors related to the attitude towards medication would offer
      an improved opportunity for clinicians to select patients eligible for
      prophylactic adherence-focused interventions.

PMID- 22969295
TI  - Assessing patient report of function: content validity of the Functional
      Performance Inventory-Short Form (FPI-SF) in patients with chronic obstructive
      pulmonary disease (COPD).
AB  - PURPOSE: The performance of daily activities is a major challenge for people with
      chronic obstructive pulmonary disease (COPD). The Functional Performance
      Inventory (FPI) was developed based on an analytical framework of functional
      status and qualitative interviews with COPD patients describing these
      difficulties. The 65-item FPI was reduced to a 32-item short form (SF) through a
      systematic process of qualitative and quantitative item reduction and formatted
      for greater clarity and ease of use. This study examined the content validity of
      the reduced, reformatted form of the instrument, the FPI-SF. PATIENTS AND
      METHODS: Qualitative cognitive interviews were conducted with COPD patients
      recruited from three geographically diverse pulmonary clinics in the United
      States. Interviews were designed to assess respondent interpretation of the
      instrument, evaluate clarity and ease of completion, and identify any new
      activities participants found important and difficult to perform that were not
      represented by the existing items. RESULTS: Twenty subjects comprised the sample;
      12 (60%) were male, 14 (70%) were Caucasian, the mean age was 63.0 +/- 11.3
      years, 12 (60%) were retired, the mean forced expiratory volume in 1 second
      (FEV(1)) was 1.5 +/- 0.5 L, and the mean percent predicted FEV(1) was 48.4% +/-
      13.1%. Participants understood the FPI-SF as intended, including instructions,
      items, and response options. Two minor formatting changes were suggested to
      improve clarity of presentation. Participants found the content of the FPI-SF to
      be comprehensive, with items covering activities they felt were important and
      often difficult to perform. CONCLUSION: These results, together with its
      development history and previously tested quantitative properties, suggest that
      the FPI-SF is content valid for use in clinical studies of COPD.

PMID- 22969297
TI  - Cytocompatible antifungal acrylic resin containing silver nanoparticles for
      dentures.
AB  - BACKGROUND: Inhibition of Candida albicans on denture resins could play a
      significant role in preventing the development of denture stomatitis. The safety
      of a new dental material with antifungal properties was analyzed in this work.
      METHODS: Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle
      discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as
      a control. Silver nanoparticles were synthesized and characterized by ultraviolet
      visible spectroscopy, dispersive Raman spectroscopy, and transmission electron
      microscopy. The antifungal effect was assessed using a luminescent microbial cell
      viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse
      embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were
      cultured for 24 or 72 hours in the presence or absence of the polymer
      formulations and analyzed using three different tests, ie, cellular viability by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and
      cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA
      damage (Comet assay). Finally, the samples were evaluated mechanically, and the
      polymer-bearing silver nanoparticles were analyzed microscopically to evaluate
      dispersion of the nanoparticles. RESULTS: The results show that PMMA-silver
      nanoparticle discs significantly reduce adherence of C. albicans and do not
      affect metabolism or proliferation. They also appear not to cause genotoxic
      damage to cells. CONCLUSION: The present work has developed a new biocompatible
      antifungal PMMA denture base material.

PMID- 22969298
TI  - Dual drug delivery system for targeting H. pylori in the stomach: preparation and
      in vitro characterization of amoxicillin-loaded Carbopol(r) nanospheres.
AB  - BACKGROUND AND METHODS: A dual (immediate/sustained-release) oral amoxicillin
      suspension was developed as a new dosage form to eradicate Helicobacter pylori.
      Carbopol(r)-loaded amoxicillin nanospheres could bind with the mucosa after
      delivery to the stomach and could increase the efficiency of the drug, providing
      both an immediate and a sustained action. RESULTS: The objective of this research
      was to develop amoxicillin nanospheres using a spray-drying technique and to
      investigate such features as their particle size, drug content, percentage yield,
      surface morphology, in vitro release, and stability. The nanospheres had a
      particle size range of 280-320 nm after optimizing the preparation method using a
      central composite design. The drug content and percentage yield was 85.3% +/-
      0.7% and 92.8% +/- 0.9%, respectively. The in vitro release profile of the
      amoxicillin nanospheres was consistent with a Korsmeyer-Peppas pattern, and the
      release after one hour was 19%, while for the original drug, amoxicillin, under
      the same conditions, 90% was released in the first 30 minutes. CONCLUSION: The
      nanospheres used in this study enabled controlled release of amoxicillin over an
      extended period of time for up to 12 hours and the formulation was stable for 12
      months.

PMID- 22969299
TI  - Chronic shoulder pain referred from thymic carcinoma: a case report and review of
      literature.
AB  - We report a case of thymic carcinoma presenting as unilateral shoulder pain for
      13 months. Before an accurate diagnosis was made, the patient received
      conservative treatment, cervical discectomies, and myofascial trigger point
      injection, none of which relieved his pain. When thymic carcinoma was eventually
      diagnosed, he received total resection of the tumor and the shoulder pain
      subsided completely. Thymic carcinoma is a rare carcinoma, and our review of the
      literature did not show shoulder pain as its initial presentation except for one
      case report. The purpose of this report is to document our clinical experience so
      that other physiatrists can include thymic carcinoma in their differential
      diagnosis of shoulder pain.

PMID- 22969296
TI  - Lung microbiology and exacerbations in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is the most common chronic
      respiratory condition in adults and is characterized by progressive airflow
      limitation that is not fully reversible. The main etiological agents linked with
      COPD are cigarette smoking and biomass exposure but respiratory infection is
      believed to play a major role in the pathogenesis of both stable COPD and in
      acute exacerbations. Acute exacerbations are associated with more rapid decline
      in lung function and impaired quality of life and are the major causes of
      morbidity and mortality in COPD. Preventing exacerbations is a major therapeutic
      goal but currently available treatments for exacerbations are not very effective.
      Historically, bacteria were considered the main infective cause of exacerbations
      but with the development of new diagnostic techniques, respiratory viruses are
      also frequently detected in COPD exacerbations. This article aims to provide a
      state-of-the art review of current knowledge regarding the role of infection in
      COPD, highlight the areas of ongoing debate and controversy, and outline emerging
      technologies and therapies that will influence future diagnostic and therapeutic
      pathways in COPD.

PMID- 22969300
TI  - Cost comparison of second-line treatment options for late stage non-small-cell
      lung cancer: cost analysis for Italy.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide (1.38
      million cancer deaths, 18.2% of the total) and of cancer morbidity (1.61 million
      new cases, 12.7% of all new cancers). Currently only three second-line non-small
      cell lung cancer (NSCLC) pharmacotherapies are licensed in the European Union:
      the chemotherapies pemetrexed and docetaxel and the epidermal growth factor
      receptor tyrosine kinase inhibitor erlotinib. These therapy alternatives have
      shown a comparable efficacy (survival benefit). In the past, cost comparisons
      showed that erlotinib was less costly compared to docetaxel, which in turn is
      cheaper than pemetrexed. Nowadays erlotinib (and docetaxel) are still less
      expensive than pemetrexed; but docetaxel lost patent protection (basic compound
      patent) at the end of 2010, so docetaxel drug costs have decreased rapidly and
      the question remains whether erlotinib is still the least costly therapy
      alternative in second-line NSCLC. MATERIAL AND METHODS: Italy was selected for
      base case analysis to compare the total therapy costs, estimated by combining
      country-specific drug costs, administration costs, and adverse event costs of
      erlotinib and generic docetaxel in second-line NSCLC therapy. Sensitivity
      analyses on central input parameters have been performed. RESULTS: The total
      costs of treating one patient with erlotinib therapy of ?5121 are lower than the
      docetaxel costs of ?6699 for the Italian health care setting. Although the drug
      costs of erlotinib are higher than generic docetaxel (incremental ?3770): the
      costs of intravenous chemotherapy administration (incremental -?4510), and the
      costs of adverse event therapy (incremental -?837) lead to higher total therapy
      costs for docetaxel compared to the epidermal growth factor receptor tyrosine
      kinase inhibitor therapy erlotinib. CONCLUSION: The cost comparison findings for
      Italy show that erlotinib is still the less costly therapy alternative in second
      line NSCLC. These results were robust to changes of central input parameters and
      robust to further potential price decreases for docetaxel.

PMID- 22969301
TI  - Renal infarction.
AB  - Renal infarction is an underdiagnosed and under-reported phenomenon, and needs to
      be diagnosed rapidly to prevent permanent loss of renal function. Renal
      infarction should be considered in the initial differential diagnosis of
      nephrolithiasis and pyelonephritis. It is often mistaken for more benign
      pathology and is worthwhile reviewing and reporting.

PMID- 22969302
TI  - An update on purple urine bag syndrome.
AB  - Purple urine bag syndrome is characterized by the urinary drainage bag turning
      purple in patients on prolonged urinary catheterization, especially those in the
      bedridden state. It is associated with bacterial urinary tract infections caused
      by indigo-producing and indirubin-producing bacteria, usually affects women, and
      is associated with alkaline urine, constipation, and a high bacterial load in the
      urine. Almost all patients with purple urine bag syndrome are catheterized due to
      significant disability, and the urinary pH is 7.0 or more. In general, intensive
      treatment with antibiotics is not recommended. Purple urine bag syndrome per se
      almost always appears to be asymptomatic and harmless. However, caution is
      needed, because some cases have been reported to show progression to severe
      disease states, so further research into the morbidity and mortality of this
      infection is warranted.

PMID- 22969303
TI  - Epstein-Barr virus-positive ileal extraosseous plasmacytoma containing
      plasmablastic lymphoma components with CD20-positive lymph node involvement.
AB  - We report a case of Epstein-Barr virus (EBV)-positive ileal extraosseous
      plasmacytoma containing plasmablastic lymphoma components with CD20-positive
      lymph node involvement. A 34-year-old healthy Japanese male developed
      intussusception due to an ileal plasmacytoma. The lesion was positive for EBV
      encoded small nuclear RNA in in situ hybridization, with the surrounding lymph
      nodes showing the expression of CD20. Tumor cells in the ileal and lymph node
      lesions contained high-grade malignant features compatible with plasmablastic
      lymphoma. Because his abdominal lymph nodes recurred 6 months after resection, he
      received six cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisolone), and had a complete remission.
      Although his case was complicated by acute promyelocytic leukemia, he has so far
      survived, recurrence-free, for more than 7.5 years after chemotherapy for
      extraosseous plasmacytoma.

PMID- 22969305
TI  - High rate of smoking in female patients with Mondor's disease in an outpatient
      clinic in Japan.
AB  - PURPOSE: Little is known about the epidemiology of Mondor's disease. The aim of
      this study was to analyze the clinical features of Mondor's disease in an
      outpatient clinic where primary care physicians are working in Japan, to better
      understand the epidemiological characteristics of the disease. PATIENTS AND
      METHODS: The data for consecutive outpatients who were new visitors to the
      Department of General Medicine in the teaching hospital (Asahikawa Medical
      University Hospital) at Asahikawa Medical University, Asahikawa, Hokkaido, Japan,
      between April 2004 and March 2012 were analyzed. Parameters such as age, sex,
      diagnosis, and clinical presentation were investigated. RESULTS: During the 8
      year period covered in this study, six (0.07%) out of 8767 patients were
      diagnosed as having Mondor's disease. All of these patients with Mondor's disease
      were female, and the mean age was 41 plus or minus 12 years; the overall rate of
      Mondor's disease in all female patients involved in this study was 0.12%. The
      patients complained of pain and a cord-like structure in the anterolateral
      thoracoabdominal wall. The painful mass had persisted for 1-4 weeks before
      presenting at the Department of General Medicine and it disappeared within a
      couple of weeks. Current smoking was significantly higher in the patients with
      Mondor's disease than in the age-matched female patients without Mondor's disease
      who were also evaluated in this study. CONCLUSION: These results suggest that a
      high rate of smoking in middle-aged females may be a characteristic feature of
      Mondor's disease. These epidemiological data may be useful in detection of the
      disease in the primary care setting in Japan.

PMID- 22969304
TI  - Factors associated with staff and physician influenza immunization at a
      children's hospital in Ontario, Canada.
AB  - In 2005, employees and physicians of the Children's Hospital of Eastern Ontario
      were surveyed about their experiences with and receipt of the 2003-2004 influenza
      vaccination. With a 29% response rate, 91% of respondents stated that they had
      received the 2003-2004 vaccine, and physicians were the most likely to have done
      so (97.2%). Using logistic regression, the only factor significantly predictive
      of whether an employee or physician received the vaccine was whether they had
      awareness of a previous formal influenza immunization campaign.

PMID- 22969306
TI  - The association between adolescent entry into the trucking industry and risk of
      HIV among long-distance truck drivers in India.
AB  - This study examines the relationship between entry into the trucking industry
      during adolescence and both sexually transmitted infections (STIs) and infection
      by the human immunodeficiency virus (HIV) among long-distance truck drivers in
      India. Data were sourced from a cross-sectional survey (sample size: 2066)
      undertaken in 2007 among long-distance truck drivers. The survey spread across
      major transshipment locations covering the bulk of India's transport volume along
      four routes. Participants were interviewed about sexual behaviors and were tested
      for HIV and STIs. The present authors constructed two synthetic cohorts based on
      the participants' duration of employment in the trucking industry: (1) low
      (duration <= 6 years) and (2) high experience (duration >= 7 years). Based on age
      at entry into the trucking industry, participants were termed as either
      adolescent (age at entry < 18 complete years) or adult entrants (age at entry >=
      18 complete years). In the low-experience cohort, the adolescent entrants were
      more likely than the adult entrants to have sex with paid female partners (42.6%
      versus 27.2%, respectively; adjusted odds ratio [OR]: 1.9; 95% confidence
      interval [CI]: 1.3-2.9) and to practice inconsistent condom use with such
      partners (69.1% versus 26.8%, respectively; adjusted OR: 5.3; 95% CI: 2.4-11.6).
      However, no significant differences were found in STI and HIV prevalence between
      the adolescent and the adult entrants in this cohort. In the high-experience
      cohort, the adolescent entrants were about two times more likely than the adult
      entrants to practice inconsistent condom use with paid female partners (38.5%
      versus 26.7%, respectively; adjusted OR: 1.7; 95% CI: 1.1-2.8) and to test
      positive for HIV (7.4% versus 4.0%, respectively; adjusted OR: 1.9; 95% CI: 1.2
      3.1) and syphilis (5.7% versus 3.5%, respectively; adjusted OR: 1.8; 95% CI: 1.1
      3.1). These results suggest the need for focused behavioral change programs in
      HIV prevention interventions for adolescent truckers in India and elsewhere.

PMID- 22969307
TI  - Health risk reduction behaviors model for scavengers exposed to solid waste in
      municipal dump sites in Nakhon Ratchasima Province, Thailand.
AB  - The aim of this study was to evaluate the effect of comprehensive health risk
      protection behaviors, knowledge, attitudes, and practices among scavengers in
      open dump sites. A control group of 44 scavengers and an intervention group of 44
      scavengers participated in this study. Interventions included the use of personal
      protective equipment, health protection training, and other measures. The
      analysis showed significant differences before and after the intervention program
      and also between the control and intervention groups. These observations suggest
      that further action should be taken to reduce adverse exposure during waste
      collection. To reduce health hazards to workers, dump site scavenging should be
      incorporated into the formal sector program. Solid waste and the management of
      municipal solid waste has become a human and environmental health issue and
      future research should look at constructing a sustainable model to help protect
      the health of scavengers and drive authorities to adopt safer management
      techniques.

PMID- 22969308
TI  - Distraction: an assessment of smartphone usage in health care work settings.
AB  - Smartphone use in health care work settings presents both opportunities and
      challenges. The benefits could be severely undermined if abuse and overuse are
      not kept in check. This practice-focused research paper examines the current
      panorama of health software applications. Findings from existing research are
      consolidated to elucidate the level and effects of distraction in health care
      work settings due to smartphone use. A conceptual framework for crafting
      guidelines to regulate the use of smartphones in health care work settings is
      then presented. Finally, specific guidelines are delineated to assist in creating
      policies for the use of smartphones in a health care workplace.

PMID- 22969310
TI  - Anthrax - Biological Threat in the 21(st) Century.

PMID- 22969309
TI  - Functional reconstruction of sarcoma defects utilising innervated free flaps.
AB  - Soft-tissue reconstruction following preoperative radiotherapy and wide resection
      of soft tissue sarcoma remains a challenge. Pedicled and free tissue transfers
      are an essential part of limb sparing surgery. We report 22 cases of sarcoma
      treated with radiotherapy and wide excision followed by one-stage innervated free
      or pedicled musculocutaneous flap transfers. The resection involved the upper
      limb in 3 cases, the lower limb in 17, and the abdominal wall in 2. The flaps
      used for the reconstruction were mainly latissimus dorsi and gracilis. The range
      of motion was restored fully in 14 patients. The muscle strength of the
      compartment reconstructed was of grades 4 and 5 in all patients except one. The
      overall function was excellent in all the cases with functional scores of 71.2%
      in the upper limb and 84% in the lower limb. The only 2 major complications were
      flap necrosis, both revised with another flap, one of which was innervated with
      restoration of function. Innervated flaps are valuable alternatives for
      reconstruction after sarcoma resection in the extremity and in the abdominal
      wall. The excellent functional results are encouraging, and we believe that
      innervated muscle reconstruction should be encouraged in the treatment of sarcoma
      after radiotherapy and wide resection.

PMID- 22969311
TI  - c-fos and its Consequences in Pain.
AB  - The discovery that c-fos, a proto-oncogene, has a role in pain, has triggered
      extensive research on the consequences of c-fos expression. It has been shown
      that c-fos, through its protein form, FOS, leads to expression of dynorphin gene
      and subsequently dynorphin protein which is implicated in the development of a
      pain state. This mini review looks at the properties of c-fos and the
      consequences of its expression following noxious (painful) stimulation.

PMID- 22969312
TI  - Vergence and accommodation system in malay primary school children.
AB  - Sixty primary school children, were measured for for accommodation and, vergence
      facility, accommodation accuracy, relative accommodation, fusional vergence /
      reserve and heterophoria.Analysis of Variance revealed that no - single factor
      was significant by involved among the six age groups for all the above (p>0.05).
      However, a significant age difference (p<0.05) was found in the fusional reserve.
      The mean and standard deviation was 20.08 (+/-6.43) cpm for the monocular
      accommodation facility, 19.77 (+/-6.26) cpm for the binocular accommodation
      facility, 20.18 (+/-5.00) cpm for the vergence facility, 0.44 (+/-0.27) D for the
      accommodation accuracy, -0.28 (+/-0.82) PD for the heterophoria at distance, 
      1.84 (+/-3.9) PD for the near heterophoria, 3.25 (+/-0.79) D for the negative
      relative accommodation, and -3.90 (+/-1.32) D for the positive relative
      accommodation.There was no age difference in the accommodation and the vergence
      status between years the ages of 7 and 12 years old but the fusional reserve
      component of the vergence system varied with age. The vergence and the
      accommodation findings in our subjects were discussed and compared with previous
      studies to serve as a guideline in clinical data interpretation and diagnosis for
      binocular vision problems in Malay children.

PMID- 22969313
TI  - The Pharmacokinetics of Single Dose vs Steady-State Doses of Propranolol in
      Cirrhotic Malay Patients.
AB  - Pharmacokinetics of propranolol (PRN) given orally were studied in twelve
      cirrhotic Malay patients [10 males, 2 females], aged 33-62 years [49.83+/-9.17],
      body weight 39-72 kg [58.0+/-8.46] and height 142-168 cm [158.8+/-7.89] following
      single 20 mg and steady-state 20 mg tds for 7 days dosing of PRN. Blood samples
      were withdrawn hourly up to 48 hours. PRN concentrations in the plasma were
      assayed by HPLC with oxprenolol as the internal standard. Pharmacokinetic
      parameters were analysed using a non-linear regression program MultiForte. Area
      under the curve (AUC) as performed using the linear trapezoidal rule. Student's t
      test was used to test for statistical significance and AUC in Malay cirrhotic
      patients was found to be much bigger than that observed in Caucasians. Steady
      state AUC was significantly increased following multiple dosing (961.31+/-7.47 vs
      2954.19+/-1153.34 ng.hr/ml), however, the volume of distribution (V(d)) declined
      (543.89+/-292.91 vs 224.14+/-1003.12 L) significantly compared to that of a
      single dose. The apparent systemic clearance (CL) was significantly reduced at
      steady-state (436.04+/-209.4 vs 129.51+/-48.42 ml/min) in comparison to single
      dose therapy. The peak plasma concentration (Cp(max)) was greatly increased at
      steady-state (54.32+/-22.37 vs 136.10+/-38.63 ng/ml). Based on the AUC, PRN
      bioavailability was greater in cirrhotic Malay patients compared to Caucasians
      who took only 20 mg instead of 80 mg doses. The decline in drug clearance
      following steady-state was due to saturation of the metabolizing capacity of
      hepatic enzymes and a decreased portal blood flow. Reduced V(d) was believed to
      be caused by increased drug-receptor interactions and decreased tissue/protein
      binding of PRN in these patients.

PMID- 22969314
TI  - Effects of sulbutiamine on diabetic polyneuropathy: an open randomised controlled
      study in type 2 diabetics.
AB  - Thirty patients with diabetic polyneuropathy were recruited from the diabetic
      clinic in Hospital Universiti Sains Malaysia from 1996 to 1998. They were
      randomly assigned either sulbutiamine (Arcalion((r))) (15 patients) or no
      treatment (control group; 15 patients). Glycaemic control was assessed by blood
      glucose and HbA1. Severity of neuropathy was assessed by symptom and sign score,
      and electrophysiological parameters (nerve conduction velocity and compound
      muscle action potential) at entry to the study and after 6 weeks. There were
      improvements in the electrophysiological parameters in the treatment group when
      compared to the controls with significant improvement in the median nerve
      conduction velocity (p<0.001), median compound muscle action potential (p<0.001),
      peroneal nerve conduction velocity (p<0.001), and peroneal compound muscle action
      potential (p<0.001). No significant improvement in symptom and sign scores were
      noted between the groups but a significant improvement compared to base line was
      noted for the sulbutiamine treated group. (p< 0.05). The glycaemic control in
      both groups was not significantly different at base line and was stable
      throughout the study. Sulbutiamine objectively improved peripheral nerve function
      in diabetic polyneuropathy although the symptom score did not improve, possibly
      due to the short duration of the study.

PMID- 22969315
TI  - Preliminary studies of left ventricular wall thickness and mass of normotensive
      and hypertensive subjects using m-mode echocardiography.
AB  - The relationship between left ventricular mass (LVM) and the mean arterial blood
      pressure (MAP) was investigated, using M-Mode echocardiography. MAP was higher in
      hypertensive patients (p<0.05, n=9) compared to that of controlled subjects. The
      results showed that LVM index for hypertensive patients was significantly higher
      (p<0.05, n=9) than that for the normal group. LVM index correlates fairly (r=0.6)
      with MAP for hypertensive patients. The results also show that the increase of
      intraventricular septal wall thickness (IVST) was due to hypertension. The LVM (r
      =0.9) and IVST (r=0.75) of the normal subjects were linearly dependent on the
      body surface area (BSA). The hypertensive group revealed a non-linear
      relationship to the BSA.

PMID- 22969316
TI  - Controversies in congenital clubfoot : literature review.
AB  - Despite common occurrence, congenital talipes equinovarus (clubfoot) is still a
      subject of controversy. It poses a significant problem with its unpredictable
      outcome, especially when the presentation for treatment is late. The true
      etiology remains unknown although many theories have been put forward. A standard
      management scheme is difficult as there is no uniformity in the pathoanatomy,
      classification and radiographic evaluation. These differ according to the age of
      the child and the severity of the condition. The paper discusses these
      controversies with an emphasis on the proposed etiologies and types of treatment
      performed.

PMID- 22969317
TI  - Postpartum depression: a survey of the incidence and associated risk factors
      among malay women in beris kubor besar, bachok, kelantan.
AB  - The aim of this study was to determine the incidence and associated risk factors
      of postpartum depression among Malay women in Beris Kubor Besar, Bachok, Kelantan
      The study was conducted between February to August 1998. A two-stage population
      survey approach was employed. Firstly, all the women who delivered between the
      months of February and May 1998 in the catchment area were identified. In stage
      1, the 30 items GHQ was used as the screening instrument at 6 to 8 weeks
      postpartum. All the potential cases (scoring above 6 on the questionnaire) were
      later interviewed using the CIS in stage 2 of the study. Diagnosis of postpartum
      depression was only made if the women fulfilled required criteria. Of the 174
      women who were recruited, 17 of them fulfilled the criteria for postpartum
      depression yielding an incidence rate of 9.8 %. The condition was found to be
      significantly linked to low income or socioeconomic status, having marital
      problems (mainly financial in nature) and not breast - feeding.

PMID- 22969318
TI  - Biliary cystadenoma - computed tomography findings.
AB  - Biliary cystadenoma is a rare neoplasm of the biliary ductal system. Surgical
      management yields an excellent result. We present a case of recurrent biliary
      cystadenoma in the left lobe of the liver. The cyst was successfully treated with
      hepatic segmentectomy. The lobulated smoothly marginated septated cystic lesion
      noted on computed tomography (CT) were highlighted and the other imaging studies,
      differential diagnosis and management were reviewed.

PMID- 22969319
TI  - Ewing's Sarcoma Mimicking Tuberculosis - A Case Report.
AB  - A 13-year old Malay school girl who had been apparently normal previously,
      presented with a three-month history of fever, malaise and loss of weight. She
      had anemia and raised values for ESR, lactic dehydrogenase, C-reactive protein,
      ferritin and a positive mantoux test. Her routine chest x-ray showed hilar
      prominence suggestive of hilar lymph node enlargement. C.T. Scan of the thorax
      revealed a posterior mediastinal mass, the histopathology of which was suggestive
      of Ewing's sarcoma. The rarity of the location of the tumour and its unusual mode
      of presentation prompted us to report this case.

PMID- 22969321
TI  - Enhancing positioning accuracy in urban terrain by fusing data from a GPS
      receiver, inertial sensors, stereo-camera and digital maps for pedestrian
      navigation.
AB  - The paper presents an algorithm for estimating a pedestrian location in an urban
      environment. The algorithm is based on the particle filter and uses different
      data sources: a GPS receiver, inertial sensors, probability maps and a stereo
      camera. Inertial sensors are used to estimate a relative displacement of a
      pedestrian. A gyroscope estimates a change in the heading direction. An
      accelerometer is used to count a pedestrian's steps and their lengths. The so
      called probability maps help to limit GPS inaccuracy by imposing constraints on
      pedestrian kinematics, e.g., it is assumed that a pedestrian cannot cross
      buildings, fences etc. This limits position inaccuracy to ca. 10 m. Incorporation
      of depth estimates derived from a stereo camera that are compared to the 3D model
      of an environment has enabled further reduction of positioning errors. As a
      result, for 90% of the time, the algorithm is able to estimate a pedestrian
      location with an error smaller than 2 m, compared to an error of 6.5 m for a
      navigation based solely on GPS.

PMID- 22969322
TI  - Meeting people's needs in a fully interoperable domotic environment.
AB  - The key idea underlying many Ambient Intelligence (AmI) projects and applications
      is context awareness, which is based mainly on their capacity to identify users
      and their locations. The actual computing capacity should remain in the
      background, in the periphery of our awareness, and should only move to the center
      if and when necessary. Computing thus becomes 'invisible', as it is embedded in
      the environment and everyday objects. The research project described herein aims
      to realize an Ambient Intelligence-based environment able to improve users'
      quality of life by learning their habits and anticipating their needs. This
      environment is part of an adaptive, context-aware framework designed to make
      today's incompatible heterogeneous domotic systems fully interoperable, not only
      for connecting sensors and actuators, but for providing comprehensive connections
      of devices to users. The solution is a middleware architecture based on open and
      widely recognized standards capable of abstracting the peculiarities of
      underlying heterogeneous technologies and enabling them to co-exist and
      interwork, without however eliminating their differences. At the highest level of
      this infrastructure, the Ambient Intelligence framework, integrated with the
      domotic sensors, can enable the system to recognize any unusual or dangerous
      situations and anticipate health problems or special user needs in a
      technological living environment, such as a house or a public space.

PMID- 22969323
TI  - Analysis of airborne particulate matter (PM2.5) over Hong Kong using remote
      sensing and GIS.
AB  - Airborne fine particulates (PM(2.5); particulate matter with diameter less than
      2.5 MUm) are receiving increasing attention for their potential toxicities and
      roles in visibility and health. In this study, we interpreted the behavior of
      PM(2.5) and its correlation with meteorological parameters in Hong Kong, during
      2007-2008. Significant diurnal variations of PM(2.5) concentrations were observed
      and showed a distinctive bimodal pattern with two marked peaks during the morning
      and evening rush hour times, due to dense traffic. The study observed higher
      PM(2.5) concentrations in winter when the northerly and northeasterly winds bring
      pollutants from the Chinese mainland, whereas southerly monsoon winds from the
      sea bring fresh air to the city in summer. In addition, higher concentrations of
      PM(2.5) were observed in rush hours on weekdays compared to weekends, suggesting
      the influence of anthropogenic activities on fine particulate levels, e.g.,
      traffic-related local PM(2.5) emissions. To understand the spatial pattern of
      PM(2.5) concentrations in the context of the built-up environment of Hong Kong,
      we utilized MODerate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical
      Thickness (AOT) 500 m data and visibility data to derive aerosol extinction
      profile, then converted to aerosol and PM(2.5) vertical profiles. A Geographic
      Information Systems (GIS) prototype was developed to integrate atmospheric
      PM(2.5) vertical profiles with 3D GIS data. An example of the query function in
      GIS prototype is given. The resulting 3D database of PM(2.5) concentrations
      provides crucial information to air quality regulators and decision makers to
      comply with air quality standards and in devising control strategies.

PMID- 22969324
TI  - An ultra-low power and flexible acoustic modem design to develop energy-efficient
      underwater sensor networks.
AB  - This paper is focused on the description of the physical layer of a new acoustic
      modem called ITACA. The modem architecture includes as a major novelty an ultra
      low power asynchronous wake-up system implementation for underwater acoustic
      transmission that is based on a low-cost off-the-shelf RFID peripheral integrated
      circuit. This feature enables a reduced power dissipation of 10 MUW in stand-by
      mode and registers very low power values during reception and transmission. The
      modem also incorporates clear channel assessment (CCA) to support CSMA-based
      medium access control (MAC) layer protocols. The design is part of a compact
      platform for a long-life short/medium range underwater wireless sensor network.

PMID- 22969325
TI  - Prediction of gap asymmetry in differential micro accelerometers.
AB  - Gap asymmetry in differential capacitors is the primary source of the zero bias
      output of force-balanced micro accelerometers. It is also used to evaluate the
      applicability of differential structures in MEMS manufacturing. Therefore,
      determining the asymmetry level has considerable significance for the design of
      MEMS devices. This paper proposes an experimental-theoretical method for
      predicting gap asymmetry in differential sensing capacitors of micro
      accelerometers. The method involves three processes: first, bi-directional
      measurement, which can sharply reduce the influence of the feedback circuit on
      bias output, is proposed. Experiments are then carried out on a centrifuge to
      obtain the input and output data of an accelerometer. Second, the analytical
      input-output relationship of the accelerometer with gap asymmetry and circuit
      error is theoretically derived. Finally, the prediction methodology combines the
      measurement results and analytical derivation to identify the asymmetric error of
      30 accelerometers fabricated by DRIE. Results indicate that the level of
      asymmetry induced by fabrication uncertainty is about +/-5 * 10(-2), and that the
      absolute error is about +/-0.2 MUm under a 4 MUm gap.

PMID- 22969326
TI  - Joint torque reduction of a three dimensional redundant planar manipulator.
AB  - Research on joint torque reduction in robot manipulators has received
      considerable attention in recent years. Minimizing the computational complexity
      of torque optimization and the ability to calculate the magnitude of the joint
      torque accurately will result in a safe operation without overloading the joint
      actuators. This paper presents a mechanical design for a three dimensional planar
      redundant manipulator with the advantage of the reduction in the number of motors
      needed to control the joint angle, leading to a decrease in the weight of the
      manipulator. Many efforts have been focused on decreasing the weight of
      manipulators, such as using lightweight joints design or setting the actuators at
      the base of the manipulator and using tendons for the transmission of power to
      these joints. By using the design of this paper, only three motors are needed to
      control any n degrees of freedom in a three dimensional planar redundant
      manipulator instead of n motors. Therefore this design is very effective to
      decrease the weight of the manipulator as well as the number of motors needed to
      control the manipulator. In this paper, the torque of all the joints are
      calculated for the proposed manipulator (with three motors) and the conventional
      three dimensional planar manipulator (with one motor for each degree of freedom)
      to show the effectiveness of the proposed manipulator for decreasing the weight
      of the manipulator and minimizing driving joint torques.

PMID- 22969327
TI  - Geometric and colour data fusion for outdoor 3D models.
AB  - This paper deals with the generation of accurate, dense and coloured 3D models of
      outdoor scenarios from scanners. This is a challenging research field in which
      several problems still remain unsolved. In particular, the process of 3D model
      creation in outdoor scenes may be inefficient if the scene is digitalized under
      unsuitable technical (specific scanner on-board camera) and environmental (rain,
      dampness, changing illumination) conditions. We address our research towards the
      integration of images and range data to produce photorealistic models. Our
      proposal is based on decoupling the colour integration and geometry
      reconstruction stages, making them independent and controlled processes. This
      issue is approached from two different viewpoints. On the one hand, given a
      complete model (geometry plus texture), we propose a method to modify the
      original texture provided by the scanner on-board camera with the colour
      information extracted from external images taken at given moments and under
      specific environmental conditions. On the other hand, we propose an algorithm to
      directly assign external images onto the complete geometric model, thus avoiding
      tedious on-line calibration processes. We present the work conducted on two large
      Roman archaeological sites dating from the first century A.D., namely, the
      Theatre of Segobriga and the Fori Porticus of Emerita Augusta, both in Spain. The
      results obtained demonstrate that our approach could be useful in the
      digitalization and 3D modelling fields.

PMID- 22969328
TI  - Ultra-fast displaying Spectral Domain Optical Doppler Tomography system using a
      Graphics Processing Unit.
AB  - We demonstrate an ultrafast displaying Spectral Domain Optical Doppler Tomography
      system using Graphics Processing Unit (GPU) computing. The calculation of FFT and
      the Doppler frequency shift is accelerated by the GPU. Our system can display
      processed OCT and ODT images simultaneously in real time at 120 fps for 1,024
      pixels * 512 lateral A-scans. The computing time for the Doppler information was
      dependent on the size of the moving average window, but with a window size of 32
      pixels the ODT computation time is only 8.3 ms, which is comparable to the data
      acquisition time. Also the phase noise decreases significantly with the window
      size. Since the performance of a real-time display for OCT/ODT is very important
      for clinical applications that need immediate diagnosis for screening or biopsy.
      Intraoperative surgery can take much benefit from the real-time display flow rate
      information from the technology. Moreover, the GPU is an attractive tool for
      clinical and commercial systems for functional OCT features as well.

PMID- 22969329
TI  - On the impact of localization and density control algorithms in target tracking
      applications for wireless sensor networks.
AB  - Target tracking is an important application of wireless sensor networks. The
      networks' ability to locate and track an object is directed linked to the nodes'
      ability to locate themselves. Consequently, localization systems are essential
      for target tracking applications. In addition, sensor networks are often deployed
      in remote or hostile environments. Therefore, density control algorithms are used
      to increase network lifetime while maintaining its sensing capabilities. In this
      work, we analyze the impact of localization algorithms (RPE and DPE) and density
      control algorithms (GAF, A3 and OGDC) on target tracking applications. We adapt
      the density control algorithms to address the k-coverage problem. In addition, we
      analyze the impact of network density, residual integration with density control,
      and k-coverage on both target tracking accuracy and network lifetime. Our results
      show that DPE is a better choice for target tracking applications than RPE.
      Moreover, among the evaluated density control algorithms, OGDC is the best option
      among the three. Although the choice of the density control algorithm has little
      impact on the tracking precision, OGDC outperforms GAF and A3 in terms of
      tracking time.

PMID- 22969330
TI  - Sensoring fusion data from the optic and acoustic emissions of electric arcs in
      the GMAW-S process for welding quality assessment.
AB  - The present study shows the relationship between welding quality and optical
      acoustic emissions from electric arcs, during welding runs, in the GMAW-S
      process. Bead on plate welding tests was carried out with pre-set parameters
      chosen from manufacturing standards. During the welding runs interferences were
      induced on the welding path using paint, grease or gas faults. In each welding
      run arc voltage, welding current, infrared and acoustic emission values were
      acquired and parameters such as arc power, acoustic peaks rate and infrared
      radiation rate computed. Data fusion algorithms were developed by assessing known
      welding quality parameters from arc emissions. These algorithms have showed
      better responses when they are based on more than just one sensor. Finally, it
      was concluded that there is a close relation between arc emissions and quality in
      welding and it can be measured from arc emissions sensing and data fusion
      algorithms.

PMID- 22969331
TI  - Single-cell electric lysis on an electroosmotic-driven microfluidic chip with
      arrays of microwells.
AB  - Accurate analysis at the single-cell level has become a highly attractive tool
      for investigating cellular content. An electroosmotic-driven microfluidic chip
      with arrays of 30-MUm-diameter microwells was developed for single-cell electric
      lysis in the present study. The cellular occupancy in the microwells when the
      applied voltage was 5 V (82.4%) was slightly higher than that at an applied
      voltage of 10 V (81.8%). When the applied voltage was increased to 15 V, the
      cellular occupancy in the microwells dropped to 64.3%. More than 50% of the
      occupied microwells contain individual cells. The results of electric lysis
      experiments at the single-cell level indicate that the cells were gradually lysed
      as the DC voltage of 30 V was applied; the cell was fully lysed after 25 s.
      Single-cell electric lysis was demonstrated in the proposed microfluidic chip,
      which is suitable for high-throughput cell lysis.

PMID- 22969332
TI  - Use of finite elements analysis for a weigh-in-motion sensor design.
AB  - High speed weigh-in-motion (WIM) sensors are utilized as components of complex
      traffic monitoring and measurement systems. They should be able to determine the
      weights on wheels, axles and vehicle gross weights, and to help the
      classification of vehicles (depending on the number of axles). WIM sensors must
      meet the following main requirements: good accuracy, high endurance, low price
      and easy installation in the road structure. It is not advisable to use cheap
      materials in constructing these devices for lower prices, since the sensors are
      normally working in harsh environmental conditions such as temperatures between 
      40  degrees C and +70  degrees C, dust, temporary water immersion, shocks and
      vibrations. Consequently, less expensive manufacturing technologies are
      recommended. Because the installation cost in the road structure is high and
      proportional to the WIM sensor cross section (especially with its thickness), the
      device needs to be made as flat as possible. The WIM sensor model presented and
      analyzed in this paper uses a spring element equipped with strain gages. Using
      Finite Element Analysis (FEA), the authors have attempted to obtain a more
      sensitive, reliable, lower profile and overall cheaper elastic element for a new
      WIM sensor.

PMID- 22969333
TI  - Ubiquitous mobile knowledge construction in collaborative learning environments.
AB  - Knowledge management is a critical activity for any organization. It has been
      said to be a differentiating factor and an important source of competitiveness if
      this knowledge is constructed and shared among its members, thus creating a
      learning organization. Knowledge construction is critical for any collaborative
      organizational learning environment. Nowadays workers must perform knowledge
      creation tasks while in motion, not just in static physical locations; therefore
      it is also required that knowledge construction activities be performed in
      ubiquitous scenarios, and supported by mobile and pervasive computational
      systems. These knowledge creation systems should help people in or outside
      organizations convert their tacit knowledge into explicit knowledge, thus
      supporting the knowledge construction process. Therefore in our understanding, we
      consider highly relevant that undergraduate university students learn about the
      knowledge construction process supported by mobile and ubiquitous computing. This
      has been a little explored issue in this field. This paper presents the design,
      implementation, and an evaluation of a system called MCKC for Mobile
      Collaborative Knowledge Construction, supporting collaborative face-to-face tacit
      knowledge construction and sharing in ubiquitous scenarios. The MCKC system can
      be used by undergraduate students to learn how to construct knowledge, allowing
      them anytime and anywhere to create, make explicit and share their knowledge with
      their co-learners, using visual metaphors, gestures and sketches to implement the
      human-computer interface of mobile devices (PDAs).

PMID- 22969334
TI  - Optical oxygen micro- and nanosensors for plant applications.
AB  - Pioneered by Clark's microelectrode more than half a century ago, there has been
      substantial interest in developing new, miniaturized optical methods to detect
      molecular oxygen inside cells. While extensively used for animal tissue
      measurements, applications of intracellular optical oxygen biosensors are still
      scarce in plant science. A critical aspect is the strong autofluorescence of the
      green plant tissue that interferes with optical signals of commonly used oxygen
      probes. A recently developed dual-frequency phase modulation technique can
      overcome this limitation, offering new perspectives for plant research. This
      review gives an overview on the latest optical sensing techniques and methods
      based on phosphorescence quenching in diverse tissues and discusses the potential
      pitfalls for applications in plants. The most promising oxygen sensitive probes
      are reviewed plus different oxygen sensing structures ranging from micro-optodes
      to soluble nanoparticles. Moreover, the applicability of using heterologously
      expressed oxygen binding proteins and fluorescent proteins to determine changes
      in the cellular oxygen concentration are discussed as potential non-invasive
      cellular oxygen reporters.

PMID- 22969335
TI  - Electrochemical determination of pentachlorophenol in water on a multi-wall
      carbon nanotubes-epoxy composite electrode.
AB  - The aim of this study was the preparation, characterization, and application of a
      multi-wall carbon nanotubes-epoxy composite electrode (MWCNT-EP) with 25%, wt.
      MWCNTs loading for the voltammetric/amperometric determination of
      pentachlorophenol (PCP) in aqueous solutions. The structural and morphological
      aspects of the MWCNT-EP composite electrode were examined by scanning electron
      microscopy. The electrical properties were characterized by direct-current
      conductivity measurements in relation with the percolation threshold. The
      electrochemical behavior of PCP at the MWCNT-EP composite electrode was
      investigated using cyclic voltammetry in 0.1 M Na2SO4 supporting electrolyte in
      order to establish the parameters for amperometric/voltammetric determination of
      PCP. The linear dependence of current vs. PCP concentrations was reached in a
      wide concentration range from 0.2 to 12 MUM PCP using cyclic voltammetry,
      differential-pulsed voltammetry, square-wave voltammetry, chronoamperometry, and
      multiple-pulsed amperometry techniques. The best electroanalytical performances
      of this composite electrode were achieved using a pre-concentration/square-wave
      voltammetric technique and also multiple-pulsed amperometry techniques envisaging
      the practical applications. The ease of preparation, high sensitivity, and
      stability of this composite electrode should open novel avenues and applications
      for fabricating robust sensors for detection of many important species.

PMID- 22969336
TI  - CMEIAS-aided microscopy of the spatial ecology of individual bacterial
      interactions involving cell-to-cell communication within biofilms.
AB  - This paper describes how the quantitative analytical tools of CMEIAS image
      analysis software can be used to investigate in situ microbial interactions
      involving cell-to-cell communication within biofilms. Various spatial pattern
      analyses applied to the data extracted from the 2-dimensional coordinate
      positioning of individual bacterial cells at single-cell resolution indicate that
      microbial colonization within natural biofilms is not a spatially random process,
      but rather involves strong positive interactions between communicating cells that
      influence their neighbors' aggregated colonization behavior. Geostatistical
      analysis of the data provide statistically defendable estimates of the micrometer
      scale and interpolation maps of the spatial heterogeneity and local intensity at
      which these microbial interactions autocorrelate with their spatial patterns of
      distribution. Including in situ image analysis in cell communication studies
      fills an important gap in understanding the spatially dependent microbial
      ecophysiology that governs the intensity of biofilm colonization and its unique
      architecture.

PMID- 22969337
TI  - RGB color calibration for quantitative image analysis: the "3D thin-plate spline"
      warping approach.
AB  - In the last years the need to numerically define color by its coordinates in n
      dimensional space has increased strongly. Colorimetric calibration is fundamental
      in food processing and other biological disciplines to quantitatively compare
      samples' color during workflow with many devices. Several software programmes are
      available to perform standardized colorimetric procedures, but they are often too
      imprecise for scientific purposes. In this study, we applied the Thin-Plate
      Spline interpolation algorithm to calibrate colours in sRGB space (the
      corresponding Matlab code is reported in the Appendix). This was compared with
      other two approaches. The first is based on a commercial calibration system
      (ProfileMaker) and the second on a Partial Least Square analysis. Moreover, to
      explore device variability and resolution two different cameras were adopted and
      for each sensor, three consecutive pictures were acquired under four different
      light conditions. According to our results, the Thin-Plate Spline approach
      reported a very high efficiency of calibration allowing the possibility to create
      a revolution in the in-field applicative context of colour quantification not
      only in food sciences, but also in other biological disciplines. These results
      are of great importance for scientific color evaluation when lighting conditions
      are not controlled. Moreover, it allows the use of low cost instruments while
      still returning scientifically sound quantitative data.

PMID- 22969339
TI  - Passive fluidic chip composed of integrated vertical capillary tubes developed
      for on-site SPR immunoassay analysis targeting real samples.
AB  - We have successfully developed a surface plasmon resonance (SPR) measurement
      system for the on-site immunoassay of real samples. The system is composed of a
      portable SPR instrument (290 mm(W) * 160 mm(D) * 120 mm(H)) and a microfluidic
      immunoassay chip (16 mm(W) * 16 mm(D) * 4 mm(H)) that needs no external pump
      system. An integrated vertical capillary tube functions as a large volume (150
      MUL) passive pump and a waste reservoir that has sufficient capacity for several
      refill operations. An immunoassay was carried out that employed the direct
      injection of a buffer and a test sample in sequence into a microfluidic chip that
      included 9 antibody bands and 10 reference reagent bands immobilized in the flow
      channel. By subtracting a reliable averaged reference sensorgram from the
      antibody, we effectively reduced the influence of the non-specific binding, and
      then our chip successfully detected the specific binding of spiked IgG in non
      homogeneous milk. IgG is a model antigen that is certain not to be present in non
      homogeneous milk, and non-homogeneous milk is a model of real sample that
      includes many interfering foreign substances that induce non-specific binding.
      The direct injection of a real sample with no pretreatment enabled us to complete
      the entire immunoassay in several minutes. This ease of operation and short
      measuring time are acceptable for on-site agricultural, environmental and medical
      testing.

PMID- 22969338
TI  - Quartz crystal microbalance aptasensor for sensitive detection of mercury(II)
      based on signal amplification with gold nanoparticles.
AB  - We show that a short mercury-specific aptamer (MSA) along with gold nanoparticles
      (Au-NPs) can be used to determine Hg(II) ion by a combination of a QCM-based
      sensor and a flow system. The MSA binds specifically to Hg(II), and the Au-NPs
      can amplify the signal to enhance sensitivity. Specifically, the short thiolated
      MSAs are immobilized on the surface of the QCM as the capture probe, and the MSAs
      are linked to the Au-NPs as the linking probe. The two components can form a
      sandwich structure of the T-Hg(II)-T type in the presence of Hg(II) ions. This
      leads to change in the mass on the QCM and a change in the resonance frequency.
      Hg(II) can be determined with a detection limit of 0.24 +/- 0.06 nM which is
      better by three orders of magnitude than previous methods. The sensor can be
      regenerated by disrupting the T-Hg(II)-T base pairs with a solution of cysteine.

PMID- 22969340
TI  - Personal pervasive environments: practice and experience.
AB  - In this paper we present our experience designing and developing two different
      systems to enable personal pervasive computing environments, Plan B and the
      Octopus. These systems were fully implemented and have been used on a daily basis
      for years. Both are based on synthetic (virtual) file system interfaces and
      provide mechanisms to adapt to changes in the context and reconfigure the system
      to support pervasive applications. We also present the main differences between
      them, focusing on architectural and reconfiguration aspects. Finally, we analyze
      the pitfalls and successes of both systems and review the lessons we learned
      while designing, developing, and using them.

PMID- 22969342
TI  - A sub-ppm acetone gas sensor for diabetes detection using 10 nm thick ultrathin
      InN FETs.
AB  - An indium nitride (InN) gas sensor of 10 nm in thickness has achieved detection
      limit of 0.4 ppm acetone. The sensor has a size of 1 mm by 2.5 mm, while its
      sensing area is 0.25 mm by 2 mm. Detection of such a low acetone concentration in
      exhaled breath could enable early diagnosis of diabetes for portable
      physiological applications. The ultrathin InN epilayer extensively enhances
      sensing sensitivity due to its strong electron accumulation on roughly 5-10 nm
      deep layers from the surface. Platinum as catalyst can increase output current
      signals by 2.5-fold (94 vs. 37.5 MUA) as well as reduce response time by 8.4-fold
      (150 vs. 1,260 s) in comparison with bare InN. More, the effect of 3% oxygen
      consumption due to breath inhalation and exhalation on 2.4 ppm acetone gas
      detection was investigated, indicating that such an acetone concentration can be
      analyzed in air.

PMID- 22969341
TI  - Advancements in transmitters and sensors for biological tissue imaging in
      magnetic induction tomography.
AB  - Magnetic Induction Tomography (MIT), which is also known as Electromagnetic
      Tomography (EMT) or Mutual Inductance Tomography, is among the imaging modalities
      of interest to many researchers around the world. This noninvasive modality
      applies an electromagnetic field and is sensitive to all three passive
      electromagnetic properties of a material that are conductivity, permittivity and
      permeability. MIT is categorized under the passive imaging family with an
      electrodeless technique through the use of excitation coils to induce an
      electromagnetic field in the material, which is then measured at the receiving
      side by sensors. The aim of this review is to discuss the challenges of the MIT
      technique and summarize the recent advancements in the transmitters and sensors,
      with a focus on applications in biological tissue imaging. It is hoped that this
      review will provide some valuable information on the MIT for those who have
      interest in this modality. The need of this knowledge may speed up the process of
      adopted of MIT as a medical imaging technology.

PMID- 22969344
TI  - Gas sensors based on one dimensional nanostructured metal-oxides: a review.
AB  - Recently one dimensional (1-D) nanostructured metal-oxides have attracted much
      attention because of their potential applications in gas sensors. 1-D
      nanostructured metal-oxides provide high surface to volume ratio, while
      maintaining good chemical and thermal stabilities with minimal power consumption
      and low weight. In recent years, various processing routes have been developed
      for the synthesis of 1-D nanostructured metal-oxides such as hydrothermal,
      ultrasonic irradiation, electrospinning, anodization, sol-gel, molten-salt,
      carbothermal reduction, solid-state chemical reaction, thermal evaporation, vapor
      phase transport, aerosol, RF sputtering, molecular beam epitaxy, chemical vapor
      deposition, gas-phase assisted nanocarving, UV lithography and dry plasma
      etching. A variety of sensor fabrication processing routes have also been
      developed. Depending on the materials, morphology and fabrication process the
      performance of the sensor towards a specific gas shows a varying degree of
      success. This article reviews and evaluates the performance of 1-D nanostructured
      metal-oxide gas sensors based on ZnO, SnO(2), TiO(2), In(2)O(3), WO(x), AgVO(3),
      CdO, MoO(3), CuO, TeO(2) and Fe(2)O(3). Advantages and disadvantages of each
      sensor are summarized, along with the associated sensing mechanism. Finally, the
      article concludes with some future directions of research.

PMID- 22969343
TI  - On-chip cellomics assay enabling algebraic and geometric understanding of
      epigenetic information in cellular networks of living systems. 1. Temporal
      aspects of epigenetic information in bacteria.
AB  - A series of studies aimed at developing methods and systems of analyzing
      epigenetic information in cells and in cell networks, as well as that of genetic
      information, was examined to expand our understanding of how living systems are
      determined. Because cells are minimum units reflecting epigenetic information,
      which is considered to map the history of a parallel-processing recurrent network
      of biochemical reactions, their behaviors cannot be explained by considering only
      conventional DNA information-processing events. The role of epigenetic
      information on cells, which complements their genetic information, was inferred
      by comparing predictions from genetic information with cell behaviour observed
      under conditions chosen to reveal adaptation processes, population effects and
      community effects. A system of analyzing epigenetic information was developed
      starting from the twin complementary viewpoints of cell regulation as an
      "algebraic" system (emphasis on temporal aspects) and as a "geometric" system
      (emphasis on spatial aspects). Exploiting the combination of latest
      microfabrication technology and measurement technologies, which we call on-chip
      cellomics assay, we can control and re-construct the environments and interaction
      of cells from "algebraic" and "geometric" viewpoints. In this review, temporal
      viewpoint of epigenetic information, a part of the series of single-cell-based
      "algebraic" and "geometric" studies of celluler systems in our research groups,
      are summerized and reported. The knowlege acquired from this study may lead to
      the use of cells that fully control practical applications like cell-based drug
      screening and the regeneration of organs.

PMID- 22969346
TI  - The camera itself as a calibration pattern: a novel self-calibration method for
      non-central catadioptric cameras.
AB  - A novel and practical self-calibration method for misaligned non-central
      catadioptric cameras is proposed in this paper. Without the aid of any special
      calibration patterns in the scene, the developed method is able to automatically
      estimate the pose parameters of the mirror with respect to the perspective
      camera. First it uses the ellipse corresponding to the mirror boundary in the
      image to compute the possible solutions for mirror postures. With two pose
      candidates, thereafter we propose a novel selection method to find the correct
      solution by using the image of the lens boundary. The whole calibration process
      is automatic and convenient to carry out since nothing more than a single image
      acquired from the catadioptric camera is needed. Experimental results both on
      synthesized and real images prove our success.

PMID- 22969347
TI  - A hybrid LPG/CFBG for highly sensitive refractive index measurements.
AB  - A simple and high sensitive method employing a hybrid long period grating
      (LPG)/chirped fiber Bragg grating (CFBG) for refractive index (RI) measurements
      is proposed and investigated experimentally. The wide wavelength range of
      backward cladding modes are excited through the coupling and recoupling between
      LPG and CFBG. Experimental results indicate that the recoupled cladding modes
      between LPG and CFBG and core mode are modulated by the surrounding RI and highly
      sensitive RI measurements can be achieved by simply measuring the reflected
      intensity changes of the recoupled cladding modes and core mode.

PMID- 22969345
TI  - Single molecule electronics and devices.
AB  - The manufacture of integrated circuits with single-molecule building blocks is a
      goal of molecular electronics. While research in the past has been limited to
      bulk experiments on self-assembled monolayers, advances in technology have now
      enabled us to fabricate single-molecule junctions. This has led to significant
      progress in understanding electron transport in molecular systems at the single
      molecule level and the concomitant emergence of new device concepts. Here, we
      review recent developments in this field. We summarize the methods currently used
      to form metal-molecule-metal structures and some single-molecule techniques
      essential for characterizing molecular junctions such as inelastic electron
      tunnelling spectroscopy. We then highlight several important achievements,
      including demonstration of single-molecule diodes, transistors, and switches that
      make use of electrical, photo, and mechanical stimulation to control the electron
      transport. We also discuss intriguing issues to be addressed further in the
      future such as heat and thermoelectric transport in an individual molecule.

PMID- 22969348
TI  - A vision-based dynamic rotational angle measurement system for large civil
      structures.
AB  - In this paper, we propose a vision-based rotational angle measurement system for
      large-scale civil structures. Despite the fact that during the last decade
      several rotation angle measurement systems were introduced, they however often
      required complex and expensive equipment. Therefore, alternative effective
      solutions with high resolution are in great demand. The proposed system consists
      of commercial PCs, commercial camcorders, low-cost frame grabbers, and a wireless
      LAN router. The calculation of rotation angle is obtained by using image
      processing techniques with pre-measured calibration parameters. Several
      laboratory tests were conducted to verify the performance of the proposed system.
      Compared with the commercial rotation angle measurement, the results of the
      system showed very good agreement with an error of less than 1.0% in all test
      cases. Furthermore, several tests were conducted on the five-story modal testing
      tower with a hybrid mass damper to experimentally verify the feasibility of the
      proposed system.

PMID- 22969349
TI  - Temperature effects on the propagation characteristics of Love waves along multi
      guide layers of Sio2/Su-8 on St-90 degrees X quartz.
AB  - Theoretical calculations have been performed on the temperature effects on the
      propagation characteristics of Love waves in layered structures by solving the
      coupled electromechanical field equations, and the optimal design parameters were
      extracted for temperature stability improvement. Based on the theoretical
      analysis, excellent temperature coefficient of frequency (Tcf) of the fabricated
      Love wave devices with guide layers of SU-8/SiO(2) on ST-90 degrees X quartz
      substrate is evaluated experimentally as only 2.16 ppm.

PMID- 22969350
TI  - A survey on the taxonomy of cluster-based routing protocols for homogeneous
      wireless sensor networks.
AB  - The past few years have witnessed increased interest among researchers in cluster
      based protocols for homogeneous networks because of their better scalability and
      higher energy efficiency than other routing protocols. Given the limited
      capabilities of sensor nodes in terms of energy resources, processing and
      communication range, the cluster-based protocols should be compatible with these
      constraints in either the setup state or steady data transmission state. With
      focus on these constraints, we classify routing protocols according to their
      objectives and methods towards addressing the shortcomings of clustering process
      on each stage of cluster head selection, cluster formation, data aggregation and
      data communication. We summarize the techniques and methods used in these
      categories, while the weakness and strength of each protocol is pointed out in
      details. Furthermore, taxonomy of the protocols in each phase is given to provide
      a deeper understanding of current clustering approaches. Ultimately based on the
      existing research, a summary of the issues and solutions of the attributes and
      characteristics of clustering approaches and some open research areas in cluster
      based routing protocols that can be further pursued are provided.

PMID- 22969351
TI  - A kernel Gabor-based weighted region covariance matrix for face recognition.
AB  - This paper proposes a novel image region descriptor for face recognition, named
      kernel Gabor-based weighted region covariance matrix (KGWRCM). As different parts
      are different effectual in characterizing and recognizing faces, we construct a
      weighting matrix by computing the similarity of each pixel within a face sample
      to emphasize features. We then incorporate the weighting matrices into a region
      covariance matrix, named weighted region covariance matrix (WRCM), to obtain the
      discriminative features of faces for recognition. Finally, to further preserve
      discriminative features in higher dimensional space, we develop the kernel Gabor
      based weighted region covariance matrix (KGWRCM). Experimental results show that
      the KGWRCM outperforms other algorithms including the kernel Gabor-based region
      covariance matrix (KGCRM).

PMID- 22969352
TI  - A urinary Bcl-2 surface acoustic wave biosensor for early ovarian cancer
      detection.
AB  - In this study, the design, fabrication, surface functionalization and
      experimental characterization of an ultrasonic MEMS biosensor for urinary anti
      apoptotic protein B-cell lymphoma 2 (Bcl-2) detection with sub ng/mL sensitivity
      is presented. It was previously shown that urinary Bcl-2 levels are reliably
      elevated during early and late stages of ovarian cancer. Our biosensor uses shear
      horizontal (SH) surface acoustic waves (SAWs) on surface functionalized ST-cut
      Quartz to quantify the mass loading change by protein adhesion to the delay path.
      SH-SAWs were generated and received by a pair of micro-fabricated interdigital
      transducers (IDTs) separated by a judiciously designed delay path. The delay path
      was surface-functionalized with monoclonal antibodies, ODMS, Protein A/G and
      Pluronic F127 for optimal Bcl-2 capture with minimal non-specific adsorption. Bcl
      2 concentrations were quantified by the resulting resonance frequency shift
      detected by a custom designed resonator circuit. The target sensitivity for
      diagnosis and identifying the stage of ovarian cancer was successfully achieved
      with demonstrated Bcl-2 detection capability of 500 pg/mL. It was also shown that
      resonance frequency shift increases linearly with increasing Bcl-2 concentration.

PMID- 22969353
TI  - Aquatic acoustic metrics interface utility for underwater sound monitoring and
      analysis.
AB  - Fishes and marine mammals may suffer a range of potential effects from exposure
      to intense underwater sound generated by anthropogenic activities such as pile
      driving, shipping, sonars, and underwater blasting. Several underwater sound
      recording (USR) devices have been built to acquire samples of the underwater
      sound generated by anthropogenic activities. Software becomes indispensable for
      processing and analyzing the audio files recorded by these USRs. In this paper,
      we provide a detailed description of a new software package, the Aquatic Acoustic
      Metrics Interface (AAMI), specifically designed for analysis of underwater sound
      recordings to provide data in metrics that facilitate evaluation of the potential
      impacts of the sound on aquatic animals. In addition to the basic functions, such
      as loading and editing audio files recorded by USRs and batch processing of sound
      files, the software utilizes recording system calibration data to compute
      important parameters in physical units. The software also facilitates comparison
      of the noise sound sample metrics with biological measures such as audiograms of
      the sensitivity of aquatic animals to the sound, integrating various components
      into a single analytical frame. The features of the AAMI software are discussed,
      and several case studies are presented to illustrate its functionality.

PMID- 22969354
TI  - Intelligent emergency stop algorithm for a manipulator using a new regression
      method.
AB  - In working environments with large manipulators, accidental collisions can cause
      severe personal injuries and can seriously damage manipulators, necessitating the
      development of an emergency stop algorithm to prevent such occurrences. In this
      paper, we propose an emergency stop system for the efficient and safe operation
      of a manipulator by applying an intelligent emergency stop algorithm. Our
      proposed intelligent algorithm considers the direction of motion of the
      manipulator. In addition, using a new regression method, the algorithm includes a
      decision step that determines whether a detected object is a collision-causing
      obstacle or a part of the manipulator. We apply our emergency stop system to a
      two-link manipulator and assess the performance of our intelligent emergency stop
      algorithm as compared with other models.

PMID- 22969355
TI  - Bluetooth based chaos synchronization using particle swarm optimization and its
      applications to image encryption.
AB  - This study used the complex dynamic characteristics of chaotic systems and
      Bluetooth to explore the topic of wireless chaotic communication secrecy and
      develop a communication security system. The PID controller for chaos
      synchronization control was applied, and the optimum parameters of this PID
      controller were obtained using a Particle Swarm Optimization (PSO) algorithm.
      Bluetooth was used to realize wireless transmissions, and a chaotic wireless
      communication security system was developed in the design concept of a chaotic
      communication security system. The experimental results show that this scheme can
      be used successfully in image encryption.

PMID- 22969356
TI  - A sensing element based on a bent and elongated grooved polymer optical fiber.
AB  - An experimental and numerical investigation is performed into the power loss
      induced in grooved polymer optical fibers (POFs) subjected to combined bending
      and elongation deformations. The power loss is examined as a function of both the
      groove depth and the bend radius. An elastic-plastic three-dimensional finite
      element model is constructed to simulate the deformation in the grooved region of
      the deformed specimens. The results indicate that the power loss increases
      significantly with an increasing bending displacement or groove depth.
      Specifically, the power loss increases to as much as 12% given a groove depth of
      1.1 mm and a bending displacement of 10 mm. Based on the experimental results, an
      empirical expression is formulated to relate the power loss with the bending
      displacement for a given groove depth. It is shown that the difference between
      the estimated power loss and the actual power loss is less than 2%.

PMID- 22969357
TI  - Study of LZ-based location prediction and its application to transportation
      recommender systems.
AB  - Predicting users' next location allows to anticipate their future context, thus
      providing additional time to be ready for that context and react consequently.
      This work is focused on a set of LZ-based algorithms (LZ, LeZi Update and Active
      LeZi) capable of learning mobility patterns and estimating the next location with
      low resource needs, which makes it possible to execute them on mobile devices.
      The original algorithms have been divided into two phases, thus being possible to
      mix them and check which combination is the best one to obtain better prediction
      accuracy or lower resource consumption. To make such comparisons, a set of GSM
      based mobility traces of 95 different users is considered. Finally, a prototype
      for mobile devices that integrates the predictors in a public transportation
      recommender system is described in order to show an example of how to take
      advantage of location prediction in an ubiquitous computing environment.

PMID- 22969358
TI  - Satellite- and epoch differenced precise point positioning based on a regional
      augmentation network.
AB  - Precise Point Positioning (PPP) has been demonstrated as a simple and effective
      approach for user positioning. The key issue in PPP is how to shorten convergence
      time and improve positioning efficiency. Recent researches mainly focus on the
      ambiguity resolution by correcting residual phase errors at a single station. The
      success of this approach (referred to hereafter as NORM-PPP) is subject to how
      rapidly one can fix wide-lane and narrow-lane ambiguities to achieve the first
      ambiguity-fixed solution. The convergence time of NORM-PPP is receiver type
      dependent, and normally takes 15-20 min. Different from the general algorithm and
      theory by which the float ambiguities are estimated and the integer ambiguities
      are fixed, we concentrate on a differential PPP approach: the satellite- and
      epoch differenced (SDED) approach. In general, the SDED approach eliminates
      receiver clocks and ambiguity parameters and thus avoids the complicated residual
      phase modeling procedure. As a further development of the SDED approach, we use a
      regional augmentation network to derive tropospheric delay and remaining un
      modeled errors at user sites. By adding these corrections and applying the Robust
      estimation, the weak mathematic properties due to the ED operation is much
      improved. Implementing this new approach, we need only two epochs of data to
      achieve PPP positioning converging to centimeter-positioning accuracy. Using
      seven days of GPS data at six CORS stations in Shanghai, we demonstrate the
      success rate, defined as the case when three directions converging to desired
      positioning accuracy of 10 cm, reaches 100% when the interval between the two
      epochs is longer than 15 min. Comparing the results of 15 min' interval to that
      of 10 min', it is observed that the position RMS improves from 2.47, 3.95, 5.78
      cm to 2.21, 3.93, 4.90 cm in the North, East and Up directions, respectively.
      Combining the SDED coordinates at the starting point and the ED relative
      coordinates thereafter, we demonstrate the performance of RTK PPP with standard
      deviation of 0.80, 1.34, 0.97 cm in the North, East and Up directions.

PMID- 22969359
TI  - Estimating sugarcane yield potential using an in-season determination of
      normalized difference vegetative index.
AB  - Estimating crop yield using remote sensing techniques has proven to be
      successful. However, sugarcane possesses unique characteristics; such as, a multi
      year cropping cycle and plant height-limiting for midseason fertilizer
      application timing. Our study objective was to determine if sugarcane yield
      potential could be estimated using an in-season estimation of normalized
      difference vegetative index (NDVI). Sensor readings were taken using the
      GreenSeeker(r) handheld sensor from 2008 to 2011 in St. Gabriel and Jeanerette,
      LA, USA. In-season estimates of yield (INSEY) values were calculated by dividing
      NDVI by thermal variables. Optimum timing for estimating sugarcane yield was
      between 601-750 GDD. In-season estimated yield values improved the yield
      potential (YP) model compared to using NDVI. Generally, INSEY value showed a
      positive exponential relationship with yield (r(2) values 0.48 and 0.42 for cane
      tonnage and sugar yield, respectively). When models were separated based on
      canopy structure there was an increase the strength of the relationship for the
      erectophile varieties (r(2) 0.53 and 0.47 for cane tonnage and sugar yield,
      respectively); however, the model for planophile varieties weakened slightly.
      Results of this study indicate using an INSEY value for predicting sugarcane
      yield shows potential of being a valuable management tool for sugarcane producers
      in Louisiana.

PMID- 22969360
TI  - A neural networks-based hybrid routing protocol for wireless mesh networks.
AB  - The networking infrastructure of wireless mesh networks (WMNs) is decentralized
      and relatively simple, but they can display reliable functioning performance
      while having good redundancy. WMNs provide Internet access for fixed and mobile
      wireless devices. Both in urban and rural areas they provide users with high
      bandwidth networks over a specific coverage area. The main problems affecting
      these networks are changes in network topology and link quality. In order to
      provide regular functioning, the routing protocol has the main influence in WMN
      implementations. In this paper we suggest a new routing protocol for WMN, based
      on good results of a proactive and reactive routing protocol, and for that reason
      it can be classified as a hybrid routing protocol. The proposed solution should
      avoid flooding and creating the new routing metric. We suggest the use of
      artificial logic-i.e., neural networks (NNs). This protocol is based on mobile
      agent technologies controlled by a Hopfield neural network. In addition to this,
      our new routing metric is based on multicriteria optimization in order to
      minimize delay and blocking probability (rejected packets or their
      retransmission). The routing protocol observes real network parameters and real
      network environments. As a result of artificial logic intelligence, the proposed
      routing protocol should maximize usage of network resources and optimize network
      performance.

PMID- 22969361
TI  - Detection of miRNA in cell cultures by using microchip electrophoresis with a
      fluorescence-labeled riboprobe.
AB  - The analysis of a microRNA (miRNA), miR-222 isolated from the PC12 cell line, was
      performed by use of the ribonuclease (RNase) protection assay, cyanine 5 (Cy5)
      labeled miR-222 riboprobe, and a Hitachi SV1210 microchip electrophoresis system,
      which can be used to evaluate the integrity of total RNA. The fluorescence
      intensity corresponding to the protected RNA fragment increased in a dose
      dependent manner with respect to the complementary-strand RNA. More highly
      sensitive detection of miRNA by microchip electrophoresis than by conventional
      method using fluorescence-labeled riboprobe could be obtained in 180 s. An
      obvious increase in miR-222 expression induced by nerve growth factor in PC12
      cells could be observed. These results clearly indicate the potential of
      microchip electrophoresis for the analysis of miRNA using RNase protection assay
      with a fluorescence-labeled riboprobe.

PMID- 22969362
TI  - Automatic detection of animals in mowing operations using thermal cameras.
AB  - During the last decades, high-efficiency farming equipment has been developed in
      the agricultural sector. This has also included efficiency improvement of moving
      techniques, which include increased working speeds and widths. Therefore, the
      risk of wild animals being accidentally injured or killed during routine farming
      operations has increased dramatically over the years. In particular, the nests of
      ground nesting bird species like grey partridge (Perdix perdix) or pheasant
      (Phasianus colchicus) are vulnerable to farming operations in their breeding
      habitat, whereas in mammals, the natural instinct of e.g., leverets of brown hare
      (Lepus europaeus) and fawns of roe deer (Capreolus capreolus) to lay low and
      still in the vegetation to avoid predators increase their risk of being killed or
      injured in farming operations. Various methods and approaches have been used to
      reduce wildlife mortality resulting from farming operations. However, since
      wildlife-friendly farming often results in lower efficiency, attempts have been
      made to develop automatic systems capable of detecting wild animals in the crop.
      Here we assessed the suitability of thermal imaging in combination with digital
      image processing to automatically detect a chicken (Gallus domesticus) and a
      rabbit (Oryctolagus cuniculus) in a grassland habitat. Throughout the different
      test scenarios, our study animals were detected with a high precision, although
      the most dense grass cover reduced the detection rate. We conclude that thermal
      imaging and digital imaging processing may be an important tool for the
      improvement of wildlife-friendly farming practices in the future.

PMID- 22969363
TI  - Analysis of the air flow generated by an air-assisted sprayer equipped with two
      axial fans using a 3D sonic anemometer.
AB  - The flow of air generated by a new design of air assisted sprayer equipped with
      two axial fans of reversed rotation was analyzed. For this goal, a 3D sonic
      anemometer has been used (accuracy: 1.5%; measurement range: 0 to 45 m/s). The
      study was divided into a static test and a dynamic test. During the static test,
      the air velocity in the working vicinity of the sprayer was measured considering
      the following machine configurations: (1) one activated fan regulated at three
      air flows (machine working as a traditional sprayer); (2) two activated fans
      regulated at three air flows for each fan. In the static test 72 measurement
      points were considered. The location of the measurement points was as follow:
      left and right sides of the sprayer; three sections of measurement (A, B and C);
      three measurement distances from the shaft of the machine (1.5 m, 2.5 m and 3.5
      m); and four measurement heights (1 m, 2 m, 3 m and 4 m). The static test results
      have shown significant differences in the module and the vertical angle of the
      air velocity vector in function of the regulations of the sprayer. In the dynamic
      test, the air velocity was measured at 2.5 m from the axis of the sprayer
      considering four measurement heights (1 m, 2 m, 3 m and 4 m). In this test, the
      sprayer regulations were: one or two activated fans; one air flow for each fan;
      forward speed of 2.8 km/h. The use of one fan (back) or two fans (back and front)
      produced significant differences on the duration of the presence of wind in the
      measurement point and on the direction of the air velocity vector. The module of
      the air velocity vector was not affected by the number of activated fans.

PMID- 22969364
TI  - An intelligent sensor array distributed system for vibration analysis and
      acoustic noise characterization of a linear switched reluctance actuator.
AB  - This paper proposes a distributed system for analysis and monitoring (DSAM) of
      vibrations and acoustic noise, which consists of an array of intelligent modules,
      sensor modules, communication bus and a host PC acting as data center. The main
      advantages of the DSAM are its modularity, scalability, and flexibility for use
      of different type of sensors/transducers, with analog or digital outputs, and for
      signals of different nature. Its final cost is also significantly lower than
      other available commercial solutions. The system is reconfigurable, can operate
      either with synchronous or asynchronous modes, with programmable sampling
      frequencies, 8-bit or 12-bit resolution and a memory buffer of 15 kbyte. It
      allows real-time data-acquisition for signals of different nature, in
      applications that require a large number of sensors, thus it is suited for
      monitoring of vibrations in Linear Switched Reluctance Actuators (LSRAs). The
      acquired data allows the full characterization of the LSRA in terms of its
      response to vibrations of structural origins, and the vibrations and acoustic
      noise emitted under normal operation. The DSAM can also be used for electrical
      machine condition monitoring, machine fault diagnosis, structural
      characterization and monitoring, among other applications.

PMID- 22969365
TI  - A new inertial aid method for high dynamic Compass signal tracking based on a
      nonlinear tracking differentiator.
AB  - In Compass/INS integrated navigation systems, feedback inertial navigation
      solutions to baseband tracking loops may eliminate receiver dynamic effects, and
      effectively improve the tracking accuracy and sensitivity. In the conventional
      inertially-aided tracking loop, the satellite-receiver line-of-sight velocity is
      used directly to adjust local carrier frequency. However, if the inertial
      solution drifts, the phase tracking error will be enlarged. By using Kalman
      filter based carrier phase tracking loop, this paper introduces a new inertial
      aid method, in which the line-of-sight jerk obtained from inertial acceleration
      by a nonlinear tracking differentiator is used to adjust relevant parameters of
      the Kalman filter's process noise matrix. Validation is achieved through high
      dynamic Compass B3 signal with line-of-sight jerk of 10 g/s collected by a GNSS
      simulator. Experimental results indicate that the new inertial aid method
      proposed in this paper is free of the impact of the receiver dynamic and inertial
      errors. Therefore, when the integrated navigation system is starting or re
      tracking after losing lock, the inertial error is absent from the navigation
      solution correction that induces large drift, and the new aid method proposed in
      this paper can track highly dynamic signals.

PMID- 22969366
TI  - A communication model to integrate the Request-Response and the Publish-Subscribe
      paradigms into ubiquitous systems.
AB  - The Request-Response (RR) paradigm is widely used in ubiquitous systems to
      exchange information in a secure, reliable and timely manner. Nonetheless, there
      is also an emerging need for adopting the Publish-Subscribe (PubSub) paradigm in
      this kind of systems, due to the advantages that this paradigm offers in
      supporting mobility by means of asynchronous, non-blocking and one-to-many
      message distribution semantics for event notification. This paper analyzes the
      strengths and weaknesses of both the RR and PubSub paradigms to support
      communications in ubiquitous systems and proposes an abstract communication model
      in order to enable their seamless integration. Thus, developers will be focused
      on communication semantics and the required quality properties, rather than be
      concerned about specific communication mechanisms. The aim is to provide
      developers with abstractions intended to decrease the complexity of integrating
      different communication paradigms commonly needed in ubiquitous systems. The
      proposal has been applied to implement a middleware and a real home automation
      system to show its applicability and benefits.

PMID- 22969367
TI  - Multichannel boron doped nanocrystalline diamond ultramicroelectrode arrays:
      design, fabrication and characterization.
AB  - We report on the fabrication and characterization of an 8 * 8 multichannel Boron
      Doped Diamond (BDD) ultramicro-electrode array (UMEA). The device combines both
      the assets of microelectrodes, resulting from conditions in mass transport from
      the bulk solution toward the electrode, and of BDD's remarkable intrinsic
      electrochemical properties. The UMEAs were fabricated using an original approach
      relying on the selective growth of diamond over pre-processed 4 inches silicon
      substrates. The prepared UMEAs were characterized by cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). The results demonstrated that the
      electrodes have exhibited a very fast electrode transfer rate (k(0)) up to 0.05
      cm.s(-1) (in a fast redox couple) and on average, a steady state limiting current
      (in a 0.5 M potassium chloride aqueous solution containing 1 mM Fe(CN)(6)(4-) ion
      at 100 mV.s(-1)) of 1.8 nA. The UMEAs are targeted for electrophysiological as
      well as analytical applications.

PMID- 22969368
TI  - An accurately controlled antagonistic shape memory alloy actuator with self
      sensing.
AB  - With the progress of miniaturization, shape memory alloy (SMA) actuators exhibit
      high energy density, self-sensing ability and ease of fabrication, which make
      them well suited for practical applications. This paper presents a self-sensing
      controlled actuator drive that was designed using antagonistic pairs of SMA
      wires. Under a certain pre-strain and duty cycle, the stress between two wires
      becomes constant. Meanwhile, the strain to resistance curve can minimize the
      hysteresis gap between the heating and the cooling paths. The curves of both
      wires are then modeled by fitting polynomials such that the measured resistance
      can be used directly to determine the difference between the testing values and
      the target strain. The hysteresis model of strains to duty cycle difference has
      been used as compensation. Accurate control is demonstrated through step response
      and sinusoidal tracking. The experimental results show that, under a combination
      control program, the root-mean-square error can be reduced to 1.093%. The limited
      bandwidth of the frequency is estimated to be 0.15 Hz. Two sets of instruments
      with three degrees of freedom are illustrated to show how this type actuator
      could be potentially implemented.

PMID- 22969369
TI  - Definition of linear color models in the RGB vector color space to detect red
      peaches in orchard images taken under natural illumination.
AB  - This work proposes the detection of red peaches in orchard images based on the
      definition of different linear color models in the RGB vector color space. The
      classification and segmentation of the pixels of the image is then performed by
      comparing the color distance from each pixel to the different previously defined
      linear color models. The methodology proposed has been tested with images
      obtained in a real orchard under natural light. The peach variety in the orchard
      was the paraguayo (Prunus persica var. platycarpa) peach with red skin. The
      segmentation results showed that the area of the red peaches in the images was
      detected with an average error of 11.6%; 19.7% in the case of bright
      illumination; 8.2% in the case of low illumination; 8.6% for occlusion up to 33%;
      12.2% in the case of occlusion between 34 and 66%; and 23% for occlusion above
      66%. Finally, a methodology was proposed to estimate the diameter of the fruits
      based on an ellipsoidal fitting. A first diameter was obtained by using all the
      contour pixels and a second diameter was obtained by rejecting some pixels of the
      contour. This approach enables a rough estimate of the fruit occlusion percentage
      range by comparing the two diameter estimates.

PMID- 22969370
TI  - Managing RFID sensors networks with a general purpose RFID middleware.
AB  - RFID middleware is anticipated to one of the main research areas in the field of
      RFID applications in the near future. The Data EPC Acquisition System (DEPCAS) is
      an original proposal designed by our group to transfer and apply fundamental
      ideas from System and Data Acquisition (SCADA) systems into the areas of RFID
      acquisition, processing and distribution systems. In this paper we focus on how
      to organize and manage generic RFID sensors (edge readers, readers, PLCs, etc...)
      inside the DEPCAS middleware. We denote by RFID Sensors Networks Management
      (RSNM) this part of DEPCAS, which is built on top of two new concepts introduced
      and developed in this work: MARC (Minimum Access Reader Command) and RRTL (RFID
      Reader Topology Language). MARC is an abstraction layer used to hide
      heterogeneous devices inside a homogeneous acquisition network. RRTL is a
      language to define RFID Reader networks and to describe the relationship between
      them (concentrator, peer to peer, master/submaster).

PMID- 22969371
TI  - PAU-SA: a synthetic aperture interferometric radiometer test bed for potential
      improvements in future missions.
AB  - The Soil Moisture and Ocean Salinity (SMOS) mission is an Earth Explorer
      Opportunity mission from the European Space Agency (ESA). Its goal is to produce
      global maps of soil moisture and ocean salinity using the Microwave Imaging
      Radiometer by Aperture Synthesis (MIRAS). The purpose of the Passive Advanced
      Unit Synthetic Aperture (PAU-SA) instrument is to study and test some potential
      improvements that could eventually be implemented in future missions using
      interferometric radiometers such as the Geoestacionary Atmosferic Sounder (GAS),
      the Precipitation and All-weather Temperature and Humidity (PATH) and the
      Geostationary Interferometric Microwave Sounder (GIMS). Both MIRAS and PAU-SA are
      Y-shaped arrays with uniformly distributed antennas, but the receiver topology
      and the processing unit are quite different. The purpose of this work is to
      identify the elements in the MIRAS's design susceptible of improvement and apply
      them in the PAU-SA instrument demonstrator, to test them in view of these future
      interferometric radiometer missions.

PMID- 22969372
TI  - Satellite remote sensing of harmful algal blooms (HABs) and a potential
      synthesized framework.
AB  - Harmful algal blooms (HABs) are severe ecological disasters threatening aquatic
      systems throughout the World, which necessitate scientific efforts in detecting
      and monitoring them. Compared with traditional in situ point observations,
      satellite remote sensing is considered as a promising technique for studying HABs
      due to its advantages of large-scale, real-time, and long-term monitoring. The
      present review summarizes the suitability of current satellite data sources and
      different algorithms for detecting HABs. It also discusses the spatial scale
      issue of HABs. Based on the major problems identified from previous literature,
      including the unsystematic understanding of HABs, the insufficient incorporation
      of satellite remote sensing, and a lack of multiple oceanographic explanations of
      the mechanisms causing HABs, this review also attempts to provide a comprehensive
      understanding of the complicated mechanism of HABs impacted by multiple
      oceanographic factors. A potential synthesized framework can be established by
      combining multiple accessible satellite remote sensing approaches including
      visual interpretation, spectra analysis, parameters retrieval and spatial
      temporal pattern analysis. This framework aims to lead to a systematic and
      comprehensive monitoring of HABs based on satellite remote sensing from multiple
      oceanographic perspectives.

PMID- 22969373
TI  - Personalized alert notifications and evacuation routes in indoor environments.
AB  - The preparedness phase is crucial in the emergency management process for
      reaching an adequate level of readiness to react to potential threats and
      hazards. During this phase, emergency plans are developed to establish, among
      other procedures, evacuation and emergency escape routes. Information and
      Communication Technologies (ICT) can support and improve these procedures
      providing appropriate, updated and accessible information to all people in the
      affected zone. Current emergency management and evacuation systems do not adapt
      information to the context and the profile of each person, so messages received
      in the emergency might be useless. In this paper, we propose a set of criteria
      that ICT-based systems could achieve in order to avoid this problem adapting
      emergency alerts and evacuation routes to different situations and people.
      Moreover, in order to prove the applicability of such criteria, we define a
      mechanism that can be used as a complement of traditional evacuation systems to
      provide personalized alerts and evacuation routes to all kinds of people during
      emergency situations in working places. This mechanism is composed by three main
      components: CAP-ONES for notifying emergency alerts, NERES for defining emergency
      plans and generating personalized evacuation routes, and iNeres as the interface
      to receive and visualize these routes on smartphones. The usability and
      understandability of proposed interface has been assessed through a user study
      performed in a fire simulation in an indoor environment. This evaluation
      demonstrated that users considered iNeres easy to understand, to learn and to
      use, and they also found very innovative the idea to use smartphones as a support
      for escaping instead of static signals on walls and doors.

PMID- 22969375
TI  - The uspIC: performing scan matching localization using an imaging sonar.
AB  - This paper presents a novel approach to localize an underwater mobile robot based
      on scan matching using a Mechanically Scanned Imaging Sonar (MSIS). When used to
      perform scan matching, this sensor presents some problems such as significant
      uncertainty in the measurements or large scan times, which lead to a motion
      induced distortion. This paper presents the uspIC, which deals with these
      problems by adopting a probabilistic scan matching strategy and by defining a
      method to strongly alleviate the motion induced distortion. Experimental results
      evaluating our approach and comparing it to previously existing methods are
      provided.

PMID- 22969374
TI  - A novel human autonomy assessment system.
AB  - This article presents a novel human autonomy assessment system for generating
      context and discovering the behaviors of older people who use ambulant services.
      Our goal is to assist caregivers in assessing possibly abnormal health conditions
      in their clients concerning their level of autonomy, thus enabling caregivers to
      take countermeasures as soon as possible.

PMID- 22969376
TI  - A temperature-insensitive cladding-etched Fiber Bragg grating using a liquid
      mixture with a negative thermo-optic coefficient.
AB  - To compensate for the temperature dependency of a standard FBG, a cladding-etched
      FBG immersed with a liquid mixture having a negative thermo-optic coefficient is
      presented, and its characteristics are investigated. The Bragg wavelength of the
      cladding-etched FBG is shifted counter to the direction of the Bragg wavelength
      shift of a conventional FBG according to the mixing ratio of glycerin to water;
      thus, the temperature-dependent Bragg wavelength shift was almost compensated by
      using a liquid mixture of water (50%) and glycerin (50%) having the negative
      thermo-optic coefficient of -5 * 10(-4)  degrees C(-1).

PMID- 22969378
TI  - Design and theoretical analysis of a resonant sensor for liquid density
      measurement.
AB  - In order to increase the accuracy of on-line liquid density measurements, a
      sensor equipped with a tuning fork as the resonant sensitive component is
      designed in this paper. It is a quasi-digital sensor with simple structure and
      high precision. The sensor is based on resonance theory and composed of a
      sensitive unit and a closed-loop control unit, where the sensitive unit consists
      of the actuator, the resonant tuning fork and the detector and the closed-loop
      control unit comprises precondition circuit, digital signal processing and
      control unit, analog-to-digital converter and digital-to-analog converter. An
      approximate parameters model of the tuning fork is established and the impact of
      liquid density, position of the tuning fork, temperature and structural
      parameters on the natural frequency of the tuning fork are also analyzed. On this
      basis, a tuning fork liquid density measurement sensor is developed. In addition,
      experimental testing on the sensor has been carried out on standard calibration
      facilities under constant 20  degrees C, and the sensor coefficients are
      calibrated. The experimental results show that the repeatability error is about
      0.03% and the accuracy is about 0.4 kg/m(3). The results also confirm that the
      method to increase the accuracy of liquid density measurement is feasible.

PMID- 22969379
TI  - Ultra low power signal oriented approach for wireless health monitoring.
AB  - In recent years there is growing pressure on the medical sector to reduce costs
      while maintaining or even improving the quality of care. A potential solution to
      this problem is real time and/or remote patient monitoring by using mobile
      devices. To achieve this, medical sensors with wireless communication,
      computational and energy harvesting capabilities are networked on, or in, the
      human body forming what is commonly called a Wireless Body Area Network (WBAN).
      We present the implementation of a novel Wake Up Receiver (WUR) in the context of
      standardised wireless protocols, in a signal-oriented WBAN environment and
      present a novel protocol intended for wireless health monitoring (WhMAC). WhMAC
      is a TDMA-based protocol with very low power consumption. It utilises WBAN
      specific features and a novel ultra low power wake up receiver technology, to
      achieve flexible and at the same time very low power wireless data transfer of
      physiological signals. As the main application is in the medical domain, or
      personal health monitoring, the protocol caters for different types of medical
      sensors. We define four sensor modes, in which the sensors can transmit data,
      depending on the sensor type and emergency level. A full power dissipation model
      is provided for the protocol, with individual hardware and application
      parameters. Finally, an example application shows the reduction in the power
      consumption for different data monitoring scenarios.

PMID- 22969377
TI  - Acetylcholinesterase immobilized on magnetic beads for pesticides detection:
      application to olive oil analysis.
AB  - This work presents the development of bioassays and biosensors for the detection
      of insecticides widely used in the treatment of olive trees. The systems are
      based on the covalent immobilisation of acetylcholinesterase on magnetic
      microbeads using either colorimetry or amperometry as detection technique. The
      magnetic beads were immobilised on screen-printed electrodes or microtitration
      plates and tested using standard solutions and real samples. The developed
      devices showed good analytical performances with limits of detection much lower
      than the maximum residue limit tolerated by international regulations, as well as
      a good reproducibility and stability.

PMID- 22969380
TI  - Palmprint Recognition Across Different Devices.
AB  - In this paper, the problem of Palmprint Recognition Across Different Devices
      (PRADD) is investigated, which has not been well studied so far. Since there is
      no publicly available PRADD image database, we created a non-contact PRADD image
      database containing 12,000 grayscale captured from 100 subjects using three
      devices, i.e., one digital camera and two smart-phones. Due to the non-contact
      image acquisition used, rotation and scale changes between different images
      captured from a same palm are inevitable. We propose a robust method to calculate
      the palm width, which can be effectively used for scale normalization of
      palmprints. On this PRADD image database, we evaluate the recognition performance
      of three different methods, i.e., subspace learning method, correlation method,
      and orientation coding based method, respectively. Experiments results show that
      orientation coding based methods achieved promising recognition performance for
      PRADD.

PMID- 22969381
TI  - Synergistic effects in the gas sensitivity of polypyrrole/single wall carbon
      nanotube composites.
AB  - Polypyrrole/single wall carbon nanotube composites were synthesized by in-situ
      chemical polymerization using pyrrole (PPy) as precursor and single wall carbon
      nanotubes (SWNTs) as additive component. Electron microscope images reveal that
      SWNTs component acts as nucleation sites for PPy growth in the form of spherical
      and cylindrical core-shell structures. The SWNTs/PPy core-shell results in thin n
      p junctions which modify the PPy bandgap and reduce the work function of
      electrons. As a result of the strong coupling, Raman and IR spectra show that the
      PPy undergoes a transition from polaron to bipolaron state, i.e., indicating an
      increase in the conductivity. In the UV-Vis spectra, the 340 nm adsorption band
      (pi*-pi transition) exhibits a red shift, while the 460 nm adsorption band
      (bipolaron transition) experiences a blue shift indicating a change in electronic
      structure and a relocation of polaron levels in the band gap of PPy. The
      modification in PPy electronic structure brings in a synergistic effect in
      sensing feature. Upon exposure to oxygen (an oxidizing agent) and NH(3) gas (a
      reducing agent), the PPy/SWNTs nanocomposite shows an enhancement in sensitivity
      exceeding ten folds in comparison with those of PPy or SWNTs.

PMID- 22969382
TI  - Reliable finite frequency filter design for networked control systems with sensor
      faults.
AB  - This paper is concerned with the reliable finite frequency filter design for
      networked control systems (NCSs) subject to quantization and data missing. Taking
      into account quantization, possible data missing and sensor stuck faults, NCSs
      are modeled in the framework of discrete time-delay switched systems, and the
      finite frequency l(2) gain is adopted for the filter design of discrete time
      delay switched systems, which is converted into a set of linear matrix inequality
      (LMI) conditions. By the virtues of the derived conditions, a procedure of
      reliable filter synthesis is presented. Further, the filter gains are
      characterized in terms of solutions to a convex optimization problem which can be
      solved by using the semi-definite programme method. Finally, an example is given
      to illustrate the effectiveness of the proposed method.

PMID- 22969383
TI  - Compiler optimizations as a countermeasure against side-channel analysis in
      MSP430-based devices.
AB  - Ambient Intelligence (AmI) requires devices everywhere, dynamic and massively
      distributed networks of low-cost nodes that, among other data, manage private
      information or control restricted operations. MSP430, a 16-bit microcontroller,
      is used in WSN platforms, as the TelosB. Physical access to devices cannot be
      restricted, so attackers consider them a target of their malicious attacks in
      order to obtain access to the network. Side-channel analysis (SCA) easily
      exploits leakages from the execution of encryption algorithms that are dependent
      on critical data to guess the key value. In this paper we present an evaluation
      framework that facilitates the analysis of the effects of compiler and backend
      optimizations on the resistance against statistical SCA. We propose an
      optimization-based software countermeasure that can be used in current low-cost
      devices to radically increase resistance against statistical SCA, analyzed with
      the new framework.

PMID- 22969384
TI  - Selective detection of NO2 using Cr-doped CuO nanorods.
AB  - CuO nanosheets, Cr-doped CuO nanosheets, and Cr-doped CuO nanorods were prepared
      by heating a slurry containing Cu-hydroxide/Cr-hydroxide. Their responses to 100
      ppm NO(2), C(2)H(5)OH, NH(3), trimethylamine, C(3)H(8), and CO were measured. For
      2.2 at% Cr-doped CuO nanorods, the response (R(a)/R(g), R(a): resistance in air,
      R(g): resistance in gas) to 100 ppm NO(2) was 134.2 at 250  degrees C, which was
      significantly higher than that of pure CuO nano-sheets (R(a)/R(g) = 7.5) and 0.76
      at% Cr-doped CuO nanosheets (R(a)/R(g) = 19.9). In addition, the sensitivity for
      NO(2) was also markedly enhanced by Cr doping. Highly sensitive and selective
      detection of NO(2) in 2.2 at% Cr-doped CuO nanorods is explained in relation to
      Cr-doping induced changes in donor density, morphology, and catalytic effects.

PMID- 22969385
TI  - An annular mechanical temperature compensation structure for gas-sealed
      capacitive pressure sensor.
AB  - A novel gas-sealed capacitive pressure sensor with a temperature compensation
      structure is reported. The pressure sensor is sealed by Au-Au diffusion bonding
      under a nitrogen ambient with a pressure of 100 kPa and integrated with a
      platinum resistor-based temperature sensor for human activity monitoring
      applications. The capacitance-pressure and capacitance-temperature
      characteristics of the gas-sealed capacitive pressure sensor without temperature
      compensation structure are calculated. It is found by simulation that a ring
      shaped structure on the diaphragm of the pressure sensor can mechanically
      suppress the thermal expansion effect of the sealed gas in the cavity. Pressure
      sensors without/with temperature compensation structures are fabricated and
      measured. Through measured results, it is verified that the calculation model is
      accurate. Using the compensation structures with a 900 MUm inner radius, the
      measured temperature coefficient is much reduced as compared to that of the
      pressure sensor without compensation. The sensitivities of the pressure sensor
      before and after compensation are almost the same in the pressure range from 80
      kPa to 100 kPa.

PMID- 22969386
TI  - On the use of sensor fusion to reduce the impact of rotational and additive noise
      in human activity recognition.
AB  - The main objective of fusion mechanisms is to increase the individual reliability
      of the systems through the use of the collectivity knowledge. Moreover, fusion
      models are also intended to guarantee a certain level of robustness. This is
      particularly required for problems such as human activity recognition where
      runtime changes in the sensor setup seriously disturb the reliability of the
      initial deployed systems. For commonly used recognition systems based on inertial
      sensors, these changes are primarily characterized as sensor rotations,
      displacements or faults related to the batteries or calibration. In this work we
      show the robustness capabilities of a sensor-weighted fusion model when dealing
      with such disturbances under different circumstances. Using the proposed method,
      up to 60% outperformance is obtained when a minority of the sensors are
      artificially rotated or degraded, independent of the level of disturbance (noise)
      imposed. These robustness capabilities also apply for any number of sensors
      affected by a low to moderate noise level. The presented fusion mechanism
      compensates the poor performance that otherwise would be obtained when just a
      single sensor is considered.

PMID- 22969387
TI  - Electronic nose based on independent component analysis combined with partial
      least squares and artificial neural networks for wine prediction.
AB  - The aim of this work is to propose an alternative way for wine classification and
      prediction based on an electronic nose (e-nose) combined with Independent
      Component Analysis (ICA) as a dimensionality reduction technique, Partial Least
      Squares (PLS) to predict sensorial descriptors and Artificial Neural Networks
      (ANNs) for classification purpose. A total of 26 wines from different regions,
      varieties and elaboration processes have been analyzed with an e-nose and tasted
      by a sensory panel. Successful results have been obtained in most cases for
      prediction and classification.

PMID- 22969388
TI  - Robust feedback zoom tracking for digital video surveillance.
AB  - Zoom tracking is an important function in video surveillance, particularly in
      traffic management and security monitoring. It involves keeping an object of
      interest in focus during the zoom operation. Zoom tracking is typically achieved
      by moving the zoom and focus motors in lenses following the so-called "trace
      curve", which shows the in-focus motor positions versus the zoom motor positions
      for a specific object distance. The main task of a zoom tracking approach is to
      accurately estimate the trace curve for the specified object. Because a
      proportional integral derivative (PID) controller has historically been
      considered to be the best controller in the absence of knowledge of the
      underlying process and its high-quality performance in motor control, in this
      paper, we propose a novel feedback zoom tracking (FZT) approach based on the
      geometric trace curve estimation and PID feedback controller. The performance of
      this approach is compared with existing zoom tracking methods in digital video
      surveillance. The real-time implementation results obtained on an actual digital
      video platform indicate that the developed FZT approach not only solves the
      traditional one-to-many mapping problem without pre-training but also improves
      the robustness for tracking moving or switching objects which is the key
      challenge in video surveillance.

PMID- 22969390
TI  - Process-in-Network: a comprehensive network processing approach.
AB  - A solid and versatile communications platform is very important in modern Ambient
      Intelligence (AmI) applications, which usually require the transmission of large
      amounts of multimedia information over a highly heterogeneous network. This
      article focuses on the concept of Process-in-Network (PIN), which is defined as
      the possibility that the network processes information as it is being
      transmitted, and introduces a more comprehensive approach than current network
      processing technologies. PIN can take advantage of waiting times in queues of
      routers, idle processing capacity in intermediate nodes, and the information that
      passes through the network.

PMID- 22969389
TI  - Novel biochip platform for nucleic acid analysis.
AB  - This manuscript describes the use of a novel biochip platform for the rapid
      analysis/identification of nucleic acids, including DNA and microRNAs, with very
      high specificity. This approach combines a unique dynamic chemistry approach for
      nucleic acid testing and analysis developed by DestiNA Genomics with the
      STMicroelectronics In-Check platform, which comprises two microfluidic optimized
      and independent PCR reaction chambers, and a sequential microarray area for
      nucleic acid capture and identification by fluorescence. With its compact bench
      top "footprint" requiring only a single technician to operate, the biochip system
      promises to transform and expand routine clinical diagnostic testing and
      screening for genetic diseases, cancers, drug toxicology and heart disease, as
      well as employment in the emerging companion diagnostics market.

PMID- 22969391
TI  - Novel platform development using an assembly of carbon nanotube, nanogold and
      immobilized RNA capture element towards rapid, selective sensing of bacteria.
AB  - This study examines the creation of a nano-featured biosensor platform designed
      for the rapid and selective detection of the bacterium Escherichia coli. The
      foundation of this sensor is carbon nanotubes decorated with gold nanoparticles
      that are modified with a specific, surface adherent ribonucleiuc acid (RNA)
      sequence element. The multi-step sensor assembly was accomplished by growing
      carbon nanotubes on a graphite substrate, the direct synthesis of gold
      nanoparticles on the nanotube surface, and the attachment of thiolated RNA to the
      bound nanoparticles. The application of the compounded nano-materials for sensor
      development has the distinct advantage of retaining the electrical behavior
      property of carbon nanotubes and, through the gold nanoparticles, incorporating
      an increased surface area for additional analyte attachment sites, thus
      increasing sensitivity. We successfully demonstrated that the coating of gold
      nanoparticles with a selective RNA sequence increased the capture of E. coli by
      189% when compared to uncoated particles. The approach to sensor formation
      detailed in this study illustrates the great potential of unique composite
      structures in the development of a multi-array, electrochemical sensor for the
      fast and sensitive detection of pathogens.

PMID- 22969393
TI  - Improved iterative calibration for triaxial accelerometers based on the optimal
      observation.
AB  - This paper presents an improved iterative nonlinear calibration method in the
      gravitational field for both low-grade and high-grade triaxial accelerometers.
      This calibration method assumes the probability density function of a Gaussian
      distribution for the raw outputs of triaxial accelerometers. A nonlinear
      criterion function is derived as the maximum likelihood estimation for the
      calibration parameters and inclination vectors, which is solved by the iterative
      estimation. First, the calibration parameters, including the scale factors,
      misalignments, biases and squared coefficients are estimated by the linear least
      squares method according to the multi-position raw outputs of triaxial
      accelerometers and the initial inclination vectors. Second, the sequence quadric
      program method is utilized to solve the nonlinear constrained optimization to
      update the inclination vectors according to the estimated calibration parameters
      and raw outputs of the triaxial accelerometers. The initial inclination vectors
      are supplied by normalizing raw outputs of triaxial accelerometers at different
      positions without any a priori knowledge. To overcome the imperfections of
      models, the optimal observation scheme is designed according to some maximum
      sensitivity principle. Simulation and experiments show good estimation accuracy
      for calibration parameters and inclination vectors.

PMID- 22969392
TI  - Accuracy and precision of equine gait event detection during walking with limb
      and trunk mounted inertial sensors.
AB  - The increased variations of temporal gait events when pathology is present are
      good candidate features for objective diagnostic tests. We hypothesised that the
      gait events hoof-on/off and stance can be detected accurately and precisely using
      features from trunk and distal limb-mounted Inertial Measurement Units (IMUs).
      Four IMUs were mounted on the distal limb and five IMUs were attached to the skin
      over the dorsal spinous processes at the withers, fourth lumbar vertebrae and
      sacrum as well as left and right tuber coxae. IMU data were synchronised to a
      force plate array and a motion capture system. Accuracy (bias) and precision (SD
      of bias) was calculated to compare force plate and IMU timings for gait events.
      Data were collected from seven horses. One hundred and twenty three (123) front
      limb steps were analysed; hoof-on was detected with a bias (SD) of -7 (23) ms,
      hoof-off with 0.7 (37) ms and front limb stance with -0.02 (37) ms. A total of
      119 hind limb steps were analysed; hoof-on was found with a bias (SD) of -4 (25)
      ms, hoof-off with 6 (21) ms and hind limb stance with 0.2 (28) ms. IMUs mounted
      on the distal limbs and sacrum can detect gait events accurately and precisely.

PMID- 22969394
TI  - Long-term outdoor reliability assessment of a wireless unit for air-quality
      monitoring based on nanostructured films integrated on micromachined platforms.
AB  - We have fabricated and tested in long-term field operating conditions a wireless
      unit for outdoor air quality monitoring. The unit is equipped with two
      multiparametric sensors, one miniaturized thermo-hygrometer, front-end analogical
      and digital electronics, and an IEEE 802.15.4 based module for wireless data
      transmission. Micromachined platforms were functionalized with nanoporous metal
      oxides to obtain multiparametric sensors, hosting gas-sensitive, anemometric and
      temperature transducers. Nanoporous metal-oxide layer was directly deposited on
      gas sensing regions of micromachined platform batches by hard-mask patterned
      supersonic cluster beam deposition. An outdoor, roadside experiment was arranged
      in downtown Milan (Italy), where one wireless sensing unit was continuously
      operated side by side with standard gas chromatographic instrumentation for air
      quality measurements. By means of a router PC, data from sensing unit and other
      instrumentation were collected, merged, and sent to a remote data storage server,
      through an UMTS device. The whole-system robustness as well as sensor dataset
      characteristics were continuously characterized over a run-time period of 18
      months.

PMID- 22969395
TI  - A novel sensor for monitoring of iron(III) ions based on porphyrins.
AB  - Three A(3)B porphyrins with mixed carboxy-, phenoxy-, pyridyl-, and dimethoxy
      substituent functionalization on the meso-phenyl groups were obtained by
      multicomponent synthesis, fully characterized and used as ionophores for
      preparing PVC-based membrane sensors selective to iron(III). The membranes have
      an ionophore:PVC:plasticizer composition ratio of 1:33:66. Sodium
      tetraphenylborate was used as additive (20 mol% relative to ionophore). The
      performance characteristics (linear concentration range, slope and selectivity)
      of the sensors were investigated. The best results were obtained for the membrane
      based on 5-(4-carboxyphenyl)-10,15,20-tris(4-phenoxyphenyl)-porphyrin plasticized
      with bis(2-ethylhexyl)sebacate, in a linear range from 1 * 10(-7)-1 * 10(-1) M
      with a slope of 21.6 mV/decade. The electrode showed high selectivity with
      respect to alkaline and heavy metal ions and a response time of 20 s. The
      influence of pH on the sensor response was studied. The sensor was used for a
      period of six weeks and the utility has been tested for the quantitative
      determination of Fe(III) in recovered solutions from spent lithium ion batteries
      and for the quantitative determination of Fe(III) in tap water samples.

PMID- 22969396
TI  - Open-WiSe: a solar powered wireless sensor network platform.
AB  - Because battery-powered nodes are required in wireless sensor networks and energy
      consumption represents an important design consideration, alternate energy
      sources are needed to provide more effective and optimal function. The main goal
      of this work is to present an energy harvesting wireless sensor network platform,
      the Open Wireless Sensor node (WiSe). The design and implementation of the solar
      powered wireless platform is described including the hardware architecture,
      firmware, and a POSIX Real-Time Kernel. A sleep and wake up strategy was
      implemented to prolong the lifetime of the wireless sensor network. This platform
      was developed as a tool for researchers investigating Wireless sensor network or
      system integrators.

PMID- 22969397
TI  - A fast MEANSHIFT algorithm-based target tracking system.
AB  - Tracking moving targets in complex scenes using an active video camera is a
      challenging task. Tracking accuracy and efficiency are two key yet generally
      incompatible aspects of a Target Tracking System (TTS). A compromise scheme will
      be studied in this paper. A fast mean-shift-based Target Tracking scheme is
      designed and realized, which is robust to partial occlusion and changes in object
      appearance. The physical simulation shows that the image signal processing speed
      is >50 frame/s.

PMID- 22969398
TI  - An indoor navigation system for the visually impaired.
AB  - Navigation in indoor environments is highly challenging for the severely visually
      impaired, particularly in spaces visited for the first time. Several solutions
      have been proposed to deal with this challenge. Although some of them have shown
      to be useful in real scenarios, they involve an important deployment effort or
      use artifacts that are not natural for blind users. This paper presents an indoor
      navigation system that was designed taking into consideration usability as the
      quality requirement to be maximized. This solution enables one to identify the
      position of a person and calculates the velocity and direction of his movements.
      Using this information, the system determines the user's trajectory, locates
      possible obstacles in that route, and offers navigation information to the user.
      The solution has been evaluated using two experimental scenarios. Although the
      results are still not enough to provide strong conclusions, they indicate that
      the system is suitable to guide visually impaired people through an unknown built
      environment.

PMID- 22969399
TI  - Experimental artifacts for morphological tweaking of chemical sensor materials:
      studies on ZnO.
AB  - Sensing mechanisms of gases on solid structures are predominantly surface
      dominated. Benign surface features in terms of small grain size, high aspect
      ratio, large surface area and open and connected porosity, are required to
      realize a successful sensor material. Such morphological artifacts are a function
      of the fabrication and processing techniques employed. In this paper, we describe
      the fabrication of monoshaped and monosized zinc oxide (ZnO) particles by a
      homogeneous precipitation method, using urea and/or hexmethyltetraamine as the
      reductant. The effect of operating conditions and experimental variables, such as
      the relative concentration of the precursors, temperature, and the aging time on
      the morphology of the resulting particles was studied systematically. These
      experimental parameters were optimized in order to achieve particles of uniform
      morphology and of narrow size distribution. Some of these particles were employed
      for the detection of ammonia gas at room temperature.

PMID- 22969400
TI  - Atomic force microscopy as a tool applied to nano/biosensors.
AB  - This review article discusses and documents the basic concepts and principles of
      nano/biosensors. More specifically, we comment on the use of Chemical Force
      Microscopy (CFM) to study various aspects of architectural and chemical design
      details of specific molecules and polymers and its influence on the control of
      chemical interactions between the Atomic Force Microscopy (AFM) tip and the
      sample. This technique is based on the fabrication of nanomechanical cantilever
      sensors (NCS) and microcantilever-based biosensors (MC-B), which can provide,
      depending on the application, rapid, sensitive, simple and low-cost in situ
      detection. Besides, it can provide high repeatability and reproducibility. Here,
      we review the applications of CFM through some application examples which should
      function as methodological questions to understand and transform this tool into a
      reliable source of data. This section is followed by a description of the
      theoretical principle and usage of the functionalized NCS and MC-B technique in
      several fields, such as agriculture, biotechnology and immunoassay. Finally, we
      hope this review will help the reader to appreciate how important the tools CFM,
      NCS and MC-B are for characterization and understanding of systems on the atomic
      scale.

PMID- 22969401
TI  - Intelligent lead: a novel HRI sensor for guide robots.
AB  - This paper addresses the introduction of a new Human Robot Interaction (HRI)
      sensor for guide robots. Guide robots for geriatric patients or the visually
      impaired should follow user's control command, keeping a certain desired distance
      allowing the user to work freely. Therefore, it is necessary to acquire control
      commands and a user's position on a real-time basis. We suggest a new sensor
      fusion system to achieve this objective and we will call this sensor the
      "intelligent lead". The objective of the intelligent lead is to acquire a stable
      distance from the user to the robot, speed-control volume and turn-control
      volume, even when the robot platform with the intelligent lead is shaken on
      uneven ground. In this paper we explain a precise Extended Kalman Filter (EKF)
      procedure for this. The intelligent lead physically consists of a Kinect sensor,
      the serial linkage attached with eight rotary encoders, and an IMU (Inertial
      Measurement Unit) and their measurements are fused by the EKF. A mobile robot was
      designed to test the performance of the proposed sensor system. After installing
      the intelligent lead in the mobile robot, several tests are conducted to verify
      that the mobile robot with the intelligent lead is capable of achieving its goal
      points while maintaining the appropriate distance between the robot and the user.
      The results show that we can use the intelligent lead proposed in this paper as a
      new HRI sensor joined a joystick and a distance measure in the mobile
      environments such as the robot and the user are moving at the same time.

PMID- 22969403
TI  - A miniature integrated multimodal sensor for measuring pH, EC and temperature for
      precision agriculture.
AB  - Making several simultaneous measurements with different kinds of sensors at the
      same location in a solution is difficult because of crosstalk between the
      sensors. In addition, because the conditions at different locations in plant beds
      differ, in situ measurements in agriculture need to be done in small localized
      areas. We have fabricated a multimodal sensor on a small Si chip in which a pH
      sensor was integrated with electrical conductivity (EC) and temperature sensors.
      An ISFET with a Si(3)N(4) membrane was used for the pH sensor. For the EC sensor,
      the electrical conductivity between platinum electrodes was measured, and the
      temperature sensor was a p-n junction diode. These are some of the most important
      measurements required for controlling the conditions in plant beds. The
      multimodal sensor can be inserted into a plant bed for in situ monitoring. To
      confirm the absence of crosstalk between the sensors, we made simultaneous
      measurements of pH, EC, and temperature of a pH buffer solution in a plant bed.
      When the solution was diluted with hot or cold water, the real time measurements
      showed changes to the EC and temperature, but no change in pH. We also
      demonstrated that our sensor was capable of simultaneous in situ measurements in
      rock wool without being affected by crosstalk.

PMID- 22969404
TI  - License plate recognition algorithm for passenger cars in Chinese residential
      areas.
AB  - This paper presents a solution for the license plate recognition problem in
      residential community administrations in China. License plate images are pre
      processed through gradation, middle value filters and edge detection. In the
      license plate localization module the number of edge points, the length of
      license plate area and the number of each line of edge points are used for
      localization. In the recognition module, the paper applies a statistical
      character method combined with a structure character method to obtain the
      characters. In addition, more models and template library for the characters
      which have less difference between each other are built. A character classifier
      is designed and a fuzzy recognition method is proposed based on the fuzzy
      decision-making method. Experiments show that the recognition accuracy rate is up
      to 92%.

PMID- 22969402
TI  - Diagnostic devices for isothermal nucleic acid amplification.
AB  - Since the development of the polymerase chain reaction (PCR) technique, genomic
      information has been retrievable from lesser amounts of DNA than previously
      possible. PCR-based amplifications require high-precision instruments to perform
      temperature cycling reactions; further, they are cumbersome for routine clinical
      use. However, the use of isothermal approaches can eliminate many complications
      associated with thermocycling. The application of diagnostic devices for
      isothermal DNA amplification has recently been studied extensively. In this
      paper, we describe the basic concepts of several isothermal amplification
      approaches and review recent progress in diagnostic device development.

PMID- 22969405
TI  - Fiber optic-based refractive index sensing at INESC Porto.
AB  - A review of refractive index measurement based on different types of optical
      fiber sensor configurations and techniques is presented. It addresses the main
      developments in the area, with particular focus on results obtained at INESC
      Porto, Portugal. The optical fiber sensing structures studied include those based
      on Bragg and long period gratings, on micro-interferometers, on plasmonic effects
      in fibers and on multimode interference in a large spectrum of standard and
      microstructured optical fibers.

PMID- 22969406
TI  - Direct measurement of mammographic X-ray spectra with a digital CdTe detection
      system.
AB  - In this work we present a detection system, based on a CdTe detector and an
      innovative digital pulse processing (DPP) system, for high-rate X-ray
      spectroscopy in mammography (1-30 keV). The DPP system performs a height and
      shape analysis of the detector pulses, sampled and digitized by a 14-bit, 100 MHz
      ADC. We show the results of the characterization of the detection system both at
      low and high photon counting rates by using monoenergetic X-ray sources and a
      nonclinical X-ray tube. The detection system exhibits excellent performance up to
      830 kcps with an energy resolution of 4.5% FWHM at 22.1 keV. Direct measurements
      of clinical molybdenum X-ray spectra were carried out by using a pinhole
      collimator and a custom alignment device. A comparison with the attenuation
      curves and the half value layer values, obtained from the measured and simulated
      spectra, from an ionization chamber and from a solid state dosimeter, also shows
      the accuracy of the measurements. These results make the proposed detection
      system a very attractive tool for both laboratory research, calibration of
      dosimeters and advanced quality controls in mammography.

PMID- 22969407
TI  - Evaluation of complexation ability using a sensor electrode chip equipped with a
      wireless screening system.
AB  - We fabricated an electrode chip with a structure coated by an insulation layer
      that contains dispersed SiO(2) adsorbent particles modified by an amino-group on
      a source-drain electrode. Voltage changes caused by chelate molecule adsorption
      onto electrode surfaces and by specific cation interactions were investigated.
      The detection of specific cations without the presence of chelate molecules on
      the free electrode was also examined. By comparing both sets of results the
      complexation ability of the studied chelate molecules onto the electrode was
      evaluated. Five pairs of source-drain electrodes(*8 arrays) were fabricated on a
      glass substrate of 20 * 30 mm in size. The individual Au/Cr (1.0/0.1 MUm
      thickness) electrodes had widths of 50 MUm and an inter-electrode interval of
      100MUm.The fabricated source-drain electrodes were further coated with an
      insulation layer comprising a porous SiO(2) particle modified amino-group to
      adsorb the chelate molecules. The electrode chip was equipped with a handy-type
      sensor signal analyzer that was mounted on an amplifier circuit using a
      MinishipTM or a system in a packaged LSI device. For electrode surfaces
      containing different adsorbed chelate molecules an increase in the sensor voltage
      depended on a combination of host-guest reactions and generally decreased in the
      following order: 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphine,
      tetrakis(p-toluenesulfonate) (TMPyP)as a Cu(2+)chelator and Cu(2+)>2-nitroso-5-[N
      n-propyl-N-(3-sulfopropyl)amino]phenol(nitroso-PSAP) as an Fe(2+)chelator and
      Fe(2+)>4,7-diphenyl-1,10-phenanthrolinedisulfonic acid, disodium salt (BPDSA) as
      an Fe(2+)chelatorand Fe(2+)>3-[3-(2,4-dimethylphenylcarbamoyl)-2
      hydroxynaphthalene-1-yl-azo]-4-hydroxybenzenesulfonic acid, sodium salt (XB-1) as
      a Mg(2+)chelator and Mg(2+)>2,9-dimethyl-4,7-diphenyl-1,10
      phenanthrolinedisulfonic acid, disodium salt (BCIDSA) as a Cu(2+)chelator and
      Cu(2+), respectively. In contrast, for the electrode surfaces with adsorbed O,O'
      bis(2-aminoethyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (GEDTA) or O,O'-bis(2
      aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid, tetrapotassium salt,
      hydrate (BAPTA) as a Ca(2+)chelator no increase in the detection voltage was
      found for all the electrode tests conducted in the presence of Ca(2+).To
      determine the differences in electrode detection, molecular orbital (MO)
      calculations of the chelate molecules and surface molecular modeling of the
      adsorbents were carried out. In accordance with frontier orbital theory, the
      lowest unoccupied MO (LUMO) of the chelate molecules can accept two lone pair
      electrons at the highest occupied MO (HOMO) of the amino group on the model
      surface structure of the SiO(2) particle. As a result, a good correlation was
      obtained between the LUMO-HOMO difference and the ion response of all the
      electrodes tested. Based on the results obtained, the order of adsorbed chelate
      molecules on adsorption particles reflects the different metal ion detection
      abilities of the electrode chips.

PMID- 22969408
TI  - Multiplex immunoassay platforms based on shape-coded poly(ethylene glycol)
      hydrogel microparticles incorporating acrylic acid.
AB  - A suspension protein microarray was developed using shape-coded poly(ethylene
      glycol) (PEG) hydrogel microparticles for potential applications in multiplex and
      high-throughput immunoassays. A simple photopatterning process produced various
      shapes of hydrogel micropatterns that were weakly bound to poly(dimethylsiloxane)
      (PDMS)-coated substrates. These micropatterns were easily detached from
      substrates during the washing process and were collected as non-spherical
      microparticles. Acrylic acids were incorporated into hydrogels, which could
      covalently immobilize proteins onto their surfaces due to the presence of
      carboxyl groups. The amount of immobilized protein increased with the amount of
      acrylic acid due to more available carboxyl groups. Saturation was reached at 25%
      v/v of acrylic acid. Immunoassays with IgG and IgM immobilized onto hydrogel
      microparticles were successfully performed with a linear concentration range from
      0 to 500 ng/mL of anti-IgG and anti-IgM, respectively. Finally, a mixture of two
      different shapes of hydrogel microparticles immobilizing IgG (circle) and IgM
      (square) was prepared and it was demonstrated that simultaneous detection of two
      different target proteins was possible without cross-talk using same fluorescence
      indicator because each immunoassay was easily identified by the shapes of
      hydrogel microparticles.

PMID- 22969411
TI  - Clade age and species richness are decoupled across the eukaryotic tree of life.
AB  - Explaining the dramatic variation in species richness across the tree of life
      remains a key challenge in evolutionary biology. At the largest phylogenetic
      scales, the extreme heterogeneity in species richness observed among different
      groups of organisms is almost certainly a function of many complex and
      interdependent factors. However, the most fundamental expectation in
      macroevolutionary studies is simply that species richness in extant clades should
      be correlated with clade age: all things being equal, older clades will have had
      more time for diversity to accumulate than younger clades. Here, we test the
      relationship between stem clade age and species richness across 1,397 major
      clades of multicellular eukaryotes that collectively account for more than 1.2
      million described species. We find no evidence that clade age predicts species
      richness at this scale. We demonstrate that this decoupling of age and richness
      is unlikely to result from variation in net diversification rates among clades.
      At the largest phylogenetic scales, contemporary patterns of species richness are
      inconsistent with unbounded diversity increase through time. These results imply
      that a fundamentally different interpretative paradigm may be needed in the study
      of phylogenetic diversity patterns in many groups of organisms.

PMID- 22969413
TI  - The air that we breathe: addressing the risks of global urbanization on health.

PMID- 22969412
TI  - Stat5 signaling specifies basal versus stress erythropoietic responses through
      distinct binary and graded dynamic modalities.
AB  - Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for
      both basal erythropoiesis and for its acceleration during hypoxic stress. A key
      challenge lies in understanding how Stat5 signaling elicits distinct functions
      during basal and stress erythropoiesis. Here we asked whether these distinct
      functions might be specified by the dynamic behavior of the Stat5 signal. We used
      flow cytometry to analyze Stat5 phosphorylation dynamics in primary
      erythropoietic tissue in vivo and in vitro, identifying two signaling modalities.
      In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but
      decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary
      signal is superseded by a high-intensity graded (analog) p-Stat5 response. We
      elucidated the biological functions of binary and graded Stat5 signaling using
      the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic
      phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling
      mode, which rescues these mice from fatal perinatal anemia by promoting binary
      survival decisions in erythroblasts. However, the absence of the graded p-Stat5
      response in the EpoR-HM mice prevents them from accelerating red cell production
      in response to stress, including a failure to upregulate the transferrin
      receptor, which we show is a novel stress target. We found that Stat5 protein
      levels decline with erythroblast differentiation, governing the transition from
      high-intensity graded signaling in early erythroblasts to low-intensity binary
      signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later
      erythroblasts into high-intensity graded signal transducers capable of eliciting
      a downstream stress response. Unlike the Stat5 protein, EpoR expression in
      erythroblasts does not limit the Stat5 signaling response, a non-Michaelian
      paradigm with therapeutic implications in myeloproliferative disease. Our
      findings show how the binary and graded modalities combine to generate high
      fidelity Stat5 signaling over the entire basal and stress Epo range. They suggest
      that dynamic behavior may encode information during STAT signal transduction.

PMID- 22969414
TI  - Correction: quantifying and analyzing the network basis of genetic complexity.
AB  - [This corrects the article on p. e1002583 in vol. 8.].

PMID- 22969415
TI  - Correction: ensemble models of neutrophil trafficking in severe sepsis.
AB  - [This corrects the article on p. e1002422 in vol. 8.].

PMID- 22969416
TI  - Human motor cortical activity is selectively phase-entrained on underlying
      rhythms.
AB  - The functional significance of electrical rhythms in the mammalian brain remains
      uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently
      decrease in amplitude during movement, and to be altered in many motor diseases.
      Here we show that the activity of neuronal populations is phase-coupled with the
      beta rhythm on rapid timescales, and describe how the strength of this relation
      changes with movement. To investigate the relationship of the beta rhythm to
      neuronal dynamics, we measured local cortical activity using arrays of subdural
      electrocorticographic (ECoG) electrodes in human patients performing simple
      movement tasks. In addition to rhythmic brain processes, ECoG potentials also
      reveal a spectrally broadband motif that reflects the aggregate neural population
      activity beneath each electrode. During movement, the amplitude of this broadband
      motif follows the dynamics of individual fingers, with somatotopically specific
      responses for different fingers at different sites on the pre-central gyrus. The
      12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent
      within sulcal boundaries and decreases in amplitude across the pre- and post
      central gyri in a diffuse manner that is not finger-specific. We find that the
      amplitude of this broadband motif is entrained on the phase of the beta rhythm,
      as well as rhythms at other frequencies, in peri-central cortex during fixation.
      During finger movement, the beta phase-entrainment is diminished or eliminated.
      We suggest that the beta rhythm may be more than a resting rhythm, and that this
      entrainment may reflect a suppressive mechanism for actively gating motor
      function.

PMID- 22969417
TI  - Dependencies among editing sites in serotonin 2C receptor mRNA.
AB  - The serotonin 2C receptor (5-HT(2C)R)-a key regulator of diverse neurological
      processes-exhibits functional variability derived from editing of its pre-mRNA by
      site-specific adenosine deamination (A-to-I pre-mRNA editing) in five distinct
      sites. Here we describe a statistical technique that was developed for analysis
      of the dependencies among the editing states of the five sites. The statistical
      significance of the observed correlations was estimated by comparing editing
      patterns in multiple individuals. For both human and rat 5-HT(2C)R, the editing
      states of the physically proximal sites A and B were found to be strongly
      dependent. In contrast, the editing states of sites C and D, which are also
      physically close, seem not to be directly dependent but instead are linked
      through the dependencies on sites A and B, respectively. We observed pronounced
      differences between the editing patterns in humans and rats: in humans site A is
      the key determinant of the editing state of the other sites, whereas in rats this
      role belongs to site B. The structure of the dependencies among the editing sites
      is notably simpler in rats than it is in humans implying more complex regulation
      of 5-HT(2C)R editing and, by inference, function in the human brain. Thus,
      exhaustive statistical analysis of the 5-HT(2C)R editing patterns indicates that
      the editing state of sites A and B is the primary determinant of the editing
      states of the other three sites, and hence the overall editing pattern. Taken
      together, these findings allow us to propose a mechanistic model of concerted
      action of ADAR1 and ADAR2 in 5-HT(2C)R editing. Statistical approach developed
      here can be applied to other cases of interdependencies among modification sites
      in RNA and proteins.

PMID- 22969418
TI  - A novel computational method identifies intra- and inter-species recombination
      events in Staphylococcus aureus and Streptococcus pneumoniae.
AB  - Advances in high-throughput DNA sequencing technologies have determined an
      explosion in the number of sequenced bacterial genomes. Comparative sequence
      analysis frequently reveals evidences of homologous recombination occurring with
      different mechanisms and rates in different species, but the large-scale use of
      computational methods to identify recombination events is hampered by their high
      computational costs. Here, we propose a new method to identify recombination
      events in large datasets of whole genome sequences. Using a filtering procedure
      of the gene conservation profiles of a test genome against a panel of strains,
      this algorithm identifies sets of contiguous genes acquired by homologous
      recombination. The locations of the recombination breakpoints are determined
      using a statistical test that is able to account for the differences in the
      natural rate of evolution between different genes. The algorithm was tested on a
      dataset of 75 genomes of Staphylococcus aureus and 50 genomes comprising
      different streptococcal species, and was able to detect intra-species
      recombination events in S. aureus and in Streptococcus pneumoniae. Furthermore,
      we found evidences of an inter-species exchange of genetic material between S.
      pneumoniae and Streptococcus mitis, a closely related commensal species that
      colonizes the same ecological niche. The method has been implemented in an R
      package, Reco, which is freely available from supplementary material, and
      provides a rapid screening tool to investigate recombination on a genome-wide
      scale from sequence data.

PMID- 22969419
TI  - Criticality is an emergent property of genetic networks that exhibit
      evolvability.
AB  - Accumulating experimental evidence suggests that the gene regulatory networks of
      living organisms operate in the critical phase, namely, at the transition between
      ordered and chaotic dynamics. Such critical dynamics of the network permits the
      coexistence of robustness and flexibility which are necessary to ensure
      homeostatic stability (of a given phenotype) while allowing for switching between
      multiple phenotypes (network states) as occurs in development and in response to
      environmental change. However, the mechanisms through which genetic networks
      evolve such critical behavior have remained elusive. Here we present an
      evolutionary model in which criticality naturally emerges from the need to
      balance between the two essential components of evolvability: phenotype
      conservation and phenotype innovation under mutations. We simulated the Darwinian
      evolution of random Boolean networks that mutate gene regulatory interactions and
      grow by gene duplication. The mutating networks were subjected to selection for
      networks that both (i) preserve all the already acquired phenotypes (dynamical
      attractor states) and (ii) generate new ones. Our results show that this
      interplay between extending the phenotypic landscape (innovation) while
      conserving the existing phenotypes (conservation) suffices to cause the evolution
      of all the networks in a population towards criticality. Furthermore, the
      networks produced by this evolutionary process exhibit structures with hubs
      (global regulators) similar to the observed topology of real gene regulatory
      networks. Thus, dynamical criticality and certain elementary topological
      properties of gene regulatory networks can emerge as a byproduct of the
      evolvability of the phenotypic landscape.

PMID- 22969420
TI  - Correlated electrostatic mutations provide a reservoir of stability in HIV
      protease.
AB  - HIV protease, an aspartyl protease crucial to the life cycle of HIV, is the
      target of many drug development programs. Though many protease inhibitors are on
      the market, protease eventually evades these drugs by mutating at a rapid pace
      and building drug resistance. The drug resistance mutations, called primary
      mutations, are often destabilizing to the enzyme and this loss of stability has
      to be compensated for. Using a coarse-grained biophysical energy model together
      with statistical inference methods, we observe that accessory mutations of
      charged residues increase protein stability, playing a key role in compensating
      for destabilizing primary drug resistance mutations. Increased stability is
      intimately related to correlations between electrostatic mutations - uncorrelated
      mutations would strongly destabilize the enzyme. Additionally, statistical
      modeling indicates that the network of correlated electrostatic mutations has a
      simple topology and has evolved to minimize frustrated interactions. The model's
      statistical coupling parameters reflect this lack of frustration and strongly
      distinguish like-charge electrostatic interactions from unlike-charge
      interactions for [Formula: see text] of the most significantly correlated double
      mutants. Finally, we demonstrate that our model has considerable predictive power
      and can be used to predict complex mutation patterns, that have not yet been
      observed due to finite sample size effects, and which are likely to exist within
      the larger patient population whose virus has not yet been sequenced.

PMID- 22969422
TI  - Antifungal drug discovery: something old and something new.

PMID- 22969423
TI  - Insights from genomics into bacterial pathogen populations.
AB  - Bacterial pathogens impose a heavy burden of disease on human populations
      worldwide. The gravest threats are posed by highly virulent respiratory
      pathogens, enteric pathogens, and HIV-associated infections. Tuberculosis alone
      is responsible for the deaths of 1.5 million people annually. Treatment options
      for bacterial pathogens are being steadily eroded by the evolution and spread of
      drug resistance. However, population-level whole genome sequencing offers new
      hope in the fight against pathogenic bacteria. By providing insights into
      bacterial evolution and disease etiology, these approaches pave the way for novel
      interventions and therapeutic targets. Sequencing populations of bacteria across
      the whole genome provides unprecedented resolution to investigate (i) within-host
      evolution, (ii) transmission history, and (iii) population structure. Moreover,
      advances in rapid benchtop sequencing herald a new era of real-time genomics in
      which sequencing and analysis can be deployed within hours in response to rapidly
      changing public health emergencies. The purpose of this review is to highlight
      the transformative effect of population genomics on bacteriology, and to consider
      the prospects for answering abiding questions such as why bacteria cause disease.

PMID- 22969424
TI  - D-alanylation of lipoteichoic acids confers resistance to cationic peptides in
      group B streptococcus by increasing the cell wall density.
AB  - Cationic antimicrobial peptides (CAMPs) serve as the first line of defense of the
      innate immune system against invading microbial pathogens. Gram-positive bacteria
      can resist CAMPs by modifying their anionic teichoic acids (TAs) with D-alanine,
      but the exact mechanism of resistance is not fully understood. Here, we utilized
      various functional and biophysical approaches to investigate the interactions of
      the human pathogen Group B Streptococcus (GBS) with a series of CAMPs having
      different properties. The data reveal that: (i) D-alanylation of lipoteichoic
      acids (LTAs) enhance GBS resistance only to a subset of CAMPs and there is a
      direct correlation between resistance and CAMPs length and charge density; (ii)
      resistance due to reduced anionic charge of LTAs is not attributed to decreased
      amounts of bound peptides to the bacteria; and (iii) D-alanylation most probably
      alters the conformation of LTAs which results in increasing the cell wall
      density, as seen by Transmission Electron Microscopy, and reduces the penetration
      of CAMPs through the cell wall. Furthermore, Atomic Force Microscopy reveals
      increased surface rigidity of the cell wall of the wild-type GBS strain to more
      than 20-fold that of the dltA mutant. We propose that D-alanylation of LTAs
      confers protection against linear CAMPs mainly by decreasing the flexibility and
      permeability of the cell wall, rather than by reducing the electrostatic
      interactions of the peptide with the cell surface. Overall, our findings uncover
      an important protective role of the cell wall against CAMPs and extend our
      understanding of mechanisms of bacterial resistance.

PMID- 22969425
TI  - BZLF1 governs CpG-methylated chromatin of Epstein-Barr Virus reversing epigenetic
      repression.
AB  - Epigenetic mechanisms are essential for the regulation of all genes in mammalian
      cells but transcriptional repression including DNA methylation are also major
      epigenetic mechanisms of defense inactivating potentially harmful pathogens.
      Epstein-Barr Virus (EBV), however, has evolved to take advantage of CpG
      methylated DNA to regulate its own biphasic life cycle. We show here that latent
      EBV DNA has an extreme composition of methylated CpG dinucleotides with a bimodal
      distribution of unmethylated or fully methylated DNA at active latent genes or
      completely repressed lytic promoters, respectively. We find this scenario
      confirmed in primary EBV-infected memory B cells in vivo. Extensive CpG
      methylation of EBV's DNA argues for a very restricted gene expression during
      latency. Above-average nucleosomal occupancy, repressive histone marks, and
      Polycomb-mediated epigenetic silencing further shield early lytic promoters from
      activation during latency. The very tight repression of viral lytic genes must be
      overcome when latent EBV enters its lytic phase and supports de novo virus
      synthesis in infected cells. The EBV-encoded and AP-1 related transcription
      factor BZLF1 overturns latency and initiates virus synthesis in latently infected
      cells. Paradoxically, BZLF1 preferentially binds to CpG-methylated motifs in key
      viral promoters for their activation. Upon BZLF1 binding, we find nucleosomes
      removed, Polycomb repression lost, and RNA polymerase II recruited to the
      activated early promoters promoting efficient lytic viral gene expression.
      Surprisingly, DNA methylation is maintained throughout this phase of viral
      reactivation and is no hindrance to active transcription of extensively CpG
      methylated viral genes as thought previously. Thus, we identify BZLF1 as a
      pioneer factor that reverses epigenetic silencing of viral DNA to allow escape
      from latency and report on a new paradigm of gene regulation.

PMID- 22969426
TI  - The ESCRT machinery is recruited by the viral BFRF1 protein to the nucleus
      associated membrane for the maturation of Epstein-Barr Virus.
AB  - The cellular endosomal sorting complex required for transport (ESCRT) machinery
      participates in membrane scission and cytoplasmic budding of many RNA viruses.
      Here, we found that expression of dominant negative ESCRT proteins caused a
      blockade of Epstein-Barr virus (EBV) release and retention of viral BFRF1 at the
      nuclear envelope. The ESCRT adaptor protein Alix was redistributed and partially
      colocalized with BFRF1 at the nuclear rim of virus replicating cells. Following
      transient transfection, BFRF1 associated with ESCRT proteins, reorganized the
      nuclear membrane and induced perinuclear vesicle formation. Multiple domains
      within BFRF1 mediated vesicle formation and Alix recruitment, whereas both Bro
      and PRR domains of Alix interacted with BFRF1. Inhibition of ESCRT machinery
      abolished BFRF1-induced vesicle formation, leading to the accumulation of viral
      DNA and capsid proteins in the nucleus of EBV-replicating cells. Overall, data
      here suggest that BFRF1 recruits the ESCRT components to modulate nuclear
      envelope for the nuclear egress of EBV.

PMID- 22969427
TI  - Unbiased mutagenesis of MHV68 LANA reveals a DNA-binding domain required for LANA
      function in vitro and in vivo.
AB  - The Latency-Associated Nuclear Antigen (LANA), encoded by ORF73, is a conserved
      gene among the gamma2-herpesviruses (rhadinoviruses). The Kaposi's Sarcoma
      Associated Herpesvirus (KSHV) LANA is consistently expressed in KSHV-associated
      malignancies. In the case of the rodent gamma2-herpesvirus, murine
      gammaherpesvirus 68 (MHV68), the LANA homolog (mLANA) is required for efficient
      virus replication, reactivation from latency and immortalization of murine fetal
      liver-derived B cells. To gain insights into mLANA function(s), knowing that KSHV
      LANA binds DNA and can modulate transcription of a variety of promoters, we
      sought out and identified a mLANA-responsive promoter which maps to the terminal
      repeat (TR) of MHV68. Notably, mLANA strongly repressed activity from this
      promoter. We extended these analyses to demonstrate direct, sequence-specific
      binding of recombinant mLANA to TR DNA by DNase I footprinting. To assess whether
      the DNA-binding and/or transcription modulating function is important in the
      known mLANA phenotypes, we generated an unbiased library of mLANA point mutants
      using error-prone PCR, and screened a large panel of mutants for repression of
      the mLANA-responsive promoter to identify loss of function mutants. Notably,
      among the mutant mLANA proteins recovered, many of the mutations are in a
      predicted EBNA-1-like DNA-binding domain. Consistent with this prediction, those
      tested displayed loss of DNA binding activity. We engineered six of these mLANA
      mutants into the MHV68 genome and tested the resulting mutant viruses for: (i)
      replication fitness; (ii) efficiency of latency establishment; and (iii)
      reactivation from latency. Interestingly, each of these mLANA-mutant viruses
      exhibited phenotypes similar to the mLANA-null mutant virus, indicating that DNA
      binding is critical for mLANA function.

PMID- 22969429
TI  - Ifitm3 limits the severity of acute influenza in mice.
AB  - Interferon-induced transmembrane (IFITM) proteins are a family of viral
      restriction factors that inhibit the entry processes of several pathogenic
      viruses, including influenza A virus (IAV), in vitro. Here we report that IAV
      infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited
      accelerated disease progression, greater mortality, and higher pulmonary and
      systemic viral burdens as compared to wild type controls. We further observed
      that the phenotype of Ifitm3-specific knockout mice was indistinguishable from
      that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target
      cells including alveolar type II pneumocytes and tracheal/bronchial respiratory
      epithelial cells. Robust Ifitm3 expression was also observed in several tissues
      in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3
      could be induced by type I and II interferons. Ifitm3 could also be upregulated
      by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate
      receptors, suggesting that multiple cytokine signals could contribute to Ifitm3
      expression in a cell or tissue-specific manner. Collectively, these findings
      establish a central role for Ifitm3 in limiting acute influenza in vivo, and
      provide further insight into Ifitm3 expression and regulation.

PMID- 22969428
TI  - Real-time transcriptional profiling of cellular and viral gene expression during
      lytic cytomegalovirus infection.
AB  - During viral infections cellular gene expression is subject to rapid alterations
      induced by both viral and antiviral mechanisms. In this study, we applied
      metabolic labeling of newly transcribed RNA with 4-thiouridine (4sU-tagging) to
      dissect the real-time kinetics of cellular and viral transcriptional activity
      during lytic murine cytomegalovirus (MCMV) infection. Microarray profiling on
      newly transcribed RNA obtained at different times during the first six hours of
      MCMV infection revealed discrete functional clusters of cellular genes regulated
      with distinct kinetics at surprising temporal resolution. Immediately upon virus
      entry, a cluster of NF-kappaB- and interferon-regulated genes was induced. Rapid
      viral counter-regulation of this coincided with a very transient DNA-damage
      response, followed by a delayed ER-stress response. Rapid counter-regulation of
      all three clusters indicated the involvement of novel viral regulators targeting
      these pathways. In addition, down-regulation of two clusters involved in cell
      differentiation (rapid repression) and cell-cycle (delayed repression) was
      observed. Promoter analysis revealed all five clusters to be associated with
      distinct transcription factors, of which NF-kappaB and c-Myc were validated to
      precisely match the respective transcriptional changes observed in newly
      transcribed RNA. 4sU-tagging also allowed us to study the real-time kinetics of
      viral gene expression in the absence of any interfering virion-associated-RNA.
      Both qRT-PCR and next-generation sequencing demonstrated a sharp peak of viral
      gene expression during the first two hours of infection including transcription
      of immediate-early, early and even well characterized late genes. Interestingly,
      this was subject to rapid gene silencing by 5-6 hours post infection. Despite the
      rapid increase in viral DNA load during viral DNA replication, transcriptional
      activity of some viral genes remained remarkably constant until late-stage
      infection, or was subject to further continuous decline. In summary, this study
      pioneers real-time transcriptional analysis during a lytic herpesvirus infection
      and highlights numerous novel regulatory aspects of virus-host-cell interaction.

PMID- 22969430
TI  - The Cyclase-associated protein Cap1 is important for proper regulation of
      infection-related morphogenesis in Magnaporthe oryzae.
AB  - Surface recognition and penetration are critical steps in the infection cycle of
      many plant pathogenic fungi. In Magnaporthe oryzae, cAMP signaling is involved in
      surface recognition and pathogenesis. Deletion of the MAC1 adenylate cyclase gene
      affected appressorium formation and plant infection. In this study, we used the
      affinity purification approach to identify proteins that are associated with Mac1
      in vivo. One of the Mac1-interacting proteins is the adenylate cyclase-associated
      protein named Cap1. CAP genes are well-conserved in phytopathogenic fungi but
      none of them have been functionally characterized. Deletion of CAP1 blocked the
      effects of a dominant RAS2 allele and resulted in defects in invasive growth and
      a reduced intracellular cAMP level. The Deltacap1 mutant was defective in germ
      tube growth, appressorium formation, and formation of typical blast lesions. Cap1
      GFP had an actin-like localization pattern, localizing to the apical regions in
      vegetative hyphae, at the periphery of developing appressoria, and in circular
      structures at the base of mature appressoria. Interestingly, Cap1, similar to
      LifeAct, did not localize to the apical regions in invasive hyphae, suggesting
      that the apical actin cytoskeleton differs between vegetative and invasive
      hyphae. Domain deletion analysis indicated that the proline-rich region P2 but
      not the actin-binding domain (AB) of Cap1 was responsible for its subcellular
      localization. Nevertheless, the AB domain of Cap1 must be important for its
      function because CAP1(DeltaAB) only partially rescued the Deltacap1 mutant.
      Furthermore, exogenous cAMP induced the formation of appressorium-like structures
      in non-germinated conidia in CAP1(DeltaAB) transformants. This novel observation
      suggested that AB domain deletion may result in overstimulation of appressorium
      formation by cAMP treatment. Overall, our results indicated that CAP1 is
      important for the activation of adenylate cyclase, appressorium morphogenesis,
      and plant infection in M. oryzae. CAP1 may also play a role in feedback
      inhibition of Ras2 signaling when Pmk1 is activated.

PMID- 22969431
TI  - OX40 facilitates control of a persistent virus infection.
AB  - During acute viral infections, clearance of the pathogen is followed by the
      contraction of the anti-viral T cell compartment. In contrast, T cell responses
      need to be maintained over a longer period of time during chronic viral
      infections in order to control viral replication and to avoid viral spreading.
      Much is known about inhibitory signals such as through PD-1 that limit T cell
      activity during chronic viral infection, but little is known about the
      stimulatory signals that allow maintenance of anti-viral T cells. Here, we show
      that the co-stimulatory molecule OX40 (CD134) is critically required in the
      context of persistent LCMV clone 13 infection. Anti-viral T cells express high
      levels of OX40 in the presence of their cognate antigen and T cells lacking the
      OX40 receptor fail to accumulate sufficiently. Moreover, the emergence of T cell
      dependent germinal center responses and LCMV-specific antibodies are severely
      impaired. Consequently, OX40-deficient mice fail to control LCMV clone 13
      infection over time, highlighting the importance of this signaling pathway during
      persistent viral infection.

PMID- 22969433
TI  - Integrative genomic analysis identifies isoleucine and CodY as regulators of
      Listeria monocytogenes virulence.
AB  - Intracellular bacterial pathogens are metabolically adapted to grow within
      mammalian cells. While these adaptations are fundamental to the ability to cause
      disease, we know little about the relationship between the pathogen's metabolism
      and virulence. Here we used an integrative Metabolic Analysis Tool that combines
      transcriptome data with genome-scale metabolic models to define the metabolic
      requirements of Listeria monocytogenes during infection. Twelve metabolic
      pathways were identified as differentially active during L. monocytogenes growth
      in macrophage cells. Intracellular replication requires de novo synthesis of
      histidine, arginine, purine, and branch chain amino acids (BCAAs), as well as
      catabolism of L-rhamnose and glycerol. The importance of each metabolic pathway
      during infection was confirmed by generation of gene knockout mutants in the
      respective pathways. Next, we investigated the association of these metabolic
      requirements in the regulation of L. monocytogenes virulence. Here we show that
      limiting BCAA concentrations, primarily isoleucine, results in robust induction
      of the master virulence activator gene, prfA, and the PrfA-regulated genes. This
      response was specific and required the nutrient responsive regulator CodY, which
      is known to bind isoleucine. Further analysis demonstrated that CodY is involved
      in prfA regulation, playing a role in prfA activation under limiting conditions
      of BCAAs. This study evidences an additional regulatory mechanism underlying L.
      monocytogenes virulence, placing CodY at the crossroads of metabolism and
      virulence.

PMID- 22969434
TI  - Rare copy number variants contribute to congenital left-sided heart disease.
AB  - Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations
      that range from bicuspid aortic valve to hypoplastic left heart syndrome. It
      contributes significantly to infant mortality and has serious implications in
      adult cardiology. Although left-sided CHD is known to be highly heritable, the
      underlying genetic determinants are largely unidentified. In this study, we
      sought to determine the impact of structural genomic variation on left-sided CHD
      and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59
      multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique
      inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD
      cohort. After stringent filtering, our gene inventory reveals 25 new candidates
      for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with
      several known syndromic loci. Conservative estimation examining the overlap of
      the prioritized gene content with CNVs present only in affected individuals in
      our cohort implies a strong effect for unique CNVs in at least 10% of left-sided
      CHD cases. Enrichment testing of gene content in all identified CNVs showed a
      significant association with angiogenesis. In this first family-based CNV study
      of left-sided CHD, we found that both co-segregating and de novo events associate
      with disease in a complex fashion at structural genomic level. Often viewed as an
      anatomically circumscript disease, a subset of left-sided CHD may in fact reflect
      more general genetic perturbations of angiogenesis and/or vascular biology.

PMID- 22969435
TI  - Normal DNA methylation dynamics in DICER1-deficient mouse embryonic stem cells.
AB  - Reduced DNA methylation has been reported in DICER1-deficient mouse ES cells.
      Reductions seen at pericentric satellite repeats have suggested that siRNAs are
      required for the proper assembly of heterochromatin. More recent studies have
      postulated that the reduced methylation is an indirect effect: the loss of Mir290
      cluster miRNAs leads to upregulation of the transcriptional repressor RBL2 that
      targets the downregulation of DNA methyltransferase (Dnmt) genes. However, the
      observations have been inconsistent. We surmised that the inconsistency could be
      related to cell line "age," given that DNA methylation is lost progressively with
      passage in DNMT-deficient ES cells. We therefore subjected Dicer1(-/-) ES cells
      to two experimental regimes to rigorously test the level of functional DNMT
      activity. First, we cultured them for a prolonged period. If DNMT activity was
      reduced, further losses of methylation would occur. Second, we measured their
      DNMT activity in a rebound DNA methylation assay: DNA methylation was stripped
      from Cre/loxP conditionally mutant Dicer1 ES cells using a shRNA targeting Dnmt1
      mRNA. Cre expression then converted these cells to Dicer1(-/-), allowing for
      DNMT1 recovery and forcing the cells to remethylate in the absence of RNAi. In
      both cases, we found functional DNMT activity to be normal. Finally, we also show
      that the level of RBL2 protein is not at excess levels in Dicer1(-/-) ES cells as
      has been assumed. These studies reveal that reduced functional DNMT activity is
      not a salient feature of DICER1-deficient ES cells. We suggest that the reduced
      DNA methylation sometimes observed in these cells could be due to stochastic
      alterations in DNA methylation patterns that could offer growth or survival
      advantages in culture, or to the dysregulation of pathways acting in opposition
      to the DNMT pathway.

PMID- 22969436
TI  - Genome-wide association studies identify heavy metal ATPase3 as the primary
      determinant of natural variation in leaf cadmium in Arabidopsis thaliana.
AB  - Understanding the mechanism of cadmium (Cd) accumulation in plants is important
      to help reduce its potential toxicity to both plants and humans through dietary
      and environmental exposure. Here, we report on a study to uncover the genetic
      basis underlying natural variation in Cd accumulation in a world-wide collection
      of 349 wild collected Arabidopsis thaliana accessions. We identified a 4-fold
      variation (0.5-2 ug Cd g(-1) dry weight) in leaf Cd accumulation when these
      accessions were grown in a controlled common garden. By combining genome-wide
      association mapping, linkage mapping in an experimental F2 population, and
      transgenic complementation, we reveal that HMA3 is the sole major locus
      responsible for the variation in leaf Cd accumulation we observe in this diverse
      population of A. thaliana accessions. Analysis of the predicted amino acid
      sequence of HMA3 from 149 A. thaliana accessions reveals the existence of 10
      major natural protein haplotypes. Association of these haplotypes with leaf Cd
      accumulation and genetics complementation experiments indicate that 5 of these
      haplotypes are active and 5 are inactive, and that elevated leaf Cd accumulation
      is associated with the reduced function of HMA3 caused by a nonsense mutation and
      polymorphisms that change two specific amino acids.

PMID- 22969438
TI  - Redetermination of the low-temperature polymorph of Li(2)MnSiO(4) from single
      crystal X-ray data.
AB  - Crystals of dilithium manganese(II) silicate were grown under high-temperature
      hydro-thermal conditions in the system LiOH-MnO(2)-SiO(2). The title compound
      crystallizes in the beta(II)-Li(3)PO(4) structure type. The coordination
      polyhedra of all cations are slightly distorted tetra-hedra (m symmetry for
      MnO(4) and SiO(4)), which are linked by corner-sharing to each other. The
      vertices of the tetra-hedra point to the same direction perpendicular to the
      distorted hexa-gonal close-packed (hcp) array of O atoms within which half of the
      tetra-hedral voids are occupied by cations. In comparison with the previous
      refinement from powder X-ray data [Dominko et al. (2006 ?). Electrochem.
      Commun.8, 217-222], the present reinvestigation from single-crystal X-ray data
      allows a more precise determination of the distribution of the Li(+) and Mn(2+)
      cations, giving a perfectly site-ordered structure model for both Li(+) and
      Mn(2+).

PMID- 22969439
TI  - Diaqua-tetra-bromidotin(IV) trihydrate.
AB  - The title compound, [SnBr(4)(H(2)O)(2)].3H(2)O, forms large colourless crystals
      in originally sealed samples of tin tetra-bromide. It constitutes the first
      structurally characterized hydrate of SnBr(4) and is isostructural with the
      corresponding -hydrate of SnCl(4). It is composed of Sn(IV) atoms octa-hedrally
      coordinated by four Br atoms and two cis-related water mol-ecules. The octa-hedra
      exhibit site symmetry 2. They are arranged into columns along [001] via medium
      strong O-H?O hydrogen bonds involving the two lattice water mol-ecules (one
      situated on a twofold rotation axis) while the chains are inter-connected via
      longer O-H?Br hydrogen bonds, forming a three-dimensional network.

PMID- 22969437
TI  - A gene family derived from transposable elements during early angiosperm
      evolution has reproductive fitness benefits in Arabidopsis thaliana.
AB  - The benefits of ever-growing numbers of sequenced eukaryotic genomes will not be
      fully realized until we learn to decipher vast stretches of noncoding DNA,
      largely composed of transposable elements. Transposable elements persist through
      self-replication, but some genes once encoded by transposable elements have,
      through a process called molecular domestication, evolved new functions that
      increase fitness. Although they have conferred numerous adaptations, the number
      of such domesticated transposable element genes remains unknown, so their
      evolutionary and functional impact cannot be fully assessed. Systematic searches
      that exploit genomic signatures of natural selection have been employed to
      identify potential domesticated genes, but their predictions have yet to be
      experimentally verified. To this end, we investigated a family of domesticated
      genes called MUSTANG (MUG), identified in a previous bioinformatic search of
      plant genomes. We show that MUG genes are functional. Mutants of Arabidopsis
      thaliana MUG genes yield phenotypes with severely reduced plant fitness through
      decreased plant size, delayed flowering, abnormal development of floral organs,
      and markedly reduced fertility. MUG genes are present in all flowering plants,
      but not in any non-flowering plant lineages, such as gymnosperms, suggesting that
      the molecular domestication of MUG may have been an integral part of early
      angiosperm evolution. This study shows that systematic searches can be successful
      at identifying functional genetic elements in noncoding regions and demonstrates
      how to combine systematic searches with reverse genetics in a fruitful way to
      decipher eukaryotic genomes.

PMID- 22969440
TI  - Pb(6)Co(9)(TeO(6))(5).
AB  - Pb(6)Co(9)(TeO(6))(5), hexa-lead(II) nona-cobalt(II) penta-tellur-ate(VI), is
      isotypic with its nickel(II) analogue. The asymmetric unit contains two Pb atoms
      (site symmetries .2., ..2), four Co atoms (..2, ..2, 3.., 3.2) two Te atoms (..2,
      3..) and six O atoms (all in general positions), with the Te and Co sites in octa
      hedral coordination environments. The crystal structure can be subdivided into
      two types of layers parallel to (001). The first layer at z ? 0.25 is made up of
      edge-sharing [CoO(6)] and [TeO(6)] octa-hedra, with 1/6 of the octa-hedral holes
      not occupied. The second layer, situated at z ? 0, consist of an alternating
      arrangement of Pb(II) atoms and of double octa-hedra that are made up from face
      sharing [CoO(6)] and [TeO(6)] octa-hedra. The two types of layers are linked
      together through corner-sharing of [CoO(6)] and [TeO(6)] octa-hedra. The Pb(II)
      atoms are situated in the cavities of the framework and are stereochemically
      active with one-sided [4]- and [6]-coordinations, respectively.

PMID- 22969441
TI  - [1-(5-Bromo-2-oxidobenzyl-idene)thio-semicarbazidato-kappa(3)O,N(1),S](pyridine
      kappaN)nickel(II).
AB  - The reaction of 5-bromo-salicyl-aldehyde thio-semicarbazone with nickel acetate
      tetra-hydrate and pyridine yielded the title compound,
      [Ni(C(8)H(6)BrN(3)OS)(C(5)H(5)N)]. The Ni(II) atom is four-coordinated in a
      square-planar environment by one deprotonated dianionic thio-semicarbazone
      ligand, acting in a tridentate chelating mode through N, O and S atoms forming
      two metalla-rings, and by one pyridine mol-ecule. The complex mol-ecules are
      linked into dimers by pairs of centrosym-metrical N-H?N inter-actions. In
      addition, mol-ecules are connected through inter-molecular Br?Br inter-actions
      [3.545 (1) A], forming chains along the b-axis direction.

PMID- 22969442
TI  - Poly[aqua-MU-bromido-(MU(2)-5-methyl-pyrazine-2-carboxyl-ato
      kappa(4)N(1),O(2):O(2),O(2'))lead(II)].
AB  - In the title coordination polymer, [PbBr(C(6)H(5)N(2)O(2))(H(2)O)](n), the Pb(II)
      atom is coordinated by one pyrazine N atom, two bridging Br atoms, a water mol
      ecule and three carboxyl-ate O atoms. Bridging by the two anions generates a
      layer structure parallel to (001); the layers are linked by O-H?N and O-H?Br
      hydrogen bonds, forming a three-dimensional network. The lone pair is
      stereochemically active, resulting in a Psi-dodeca-hedral coordination
      environment for Pb(II).

PMID- 22969443
TI  - catena-Poly[[(1,3-dimethyl-imidazolin-2-one-kappaN)(1,10-phenanthroline
      kappa(2)N,N')copper(II)]-MU-furan-2,5-dicarboxyl-ato-kappa(2)O(2):O(5)].
AB  - The polymeric title compound,
      [Cu(C(6)H(2)O(5))(C(12)H(8)N(2))(C(5)H(10)N(2)O)](n), is composed of an infinite
      chain formed along [100] by linking the (1,3-dimethyl-imidazolin-2-one)(1,10
      phenanthroline)copper(II) units with two O atoms of two carboxyl-ate groups of
      the furan-2,5-dicarboxyl-ate ligand. The Cu(II) atom, which lies on a twofold
      rotation axis, displays a square-pyramidal coordination. The dihedral angles of
      the 1,10-phenanthroline ligand with respect to the furan rings of the carboxyl
      ate anions that are connected to the metal atom are 62.18 (11) and 88.27 (12)
      degrees .

PMID- 22969444
TI  - Tetra-bromido(di-2-pyridyl-amine-kappa(2)N(2),N(2'))platinum(IV).
AB  - The Pt(IV) ion in the title complex, [PtBr(4)(C(10)H(9)N(3))], is six-coordinated
      in a slightly distorted octa-hedral environment by two pyridine N atoms from a
      chelating di-2-pyridyl-amine (dpa) ligand and four Br(-) anions. The complex mol
      ecule has mirror symmetry, with the Pt(IV) atom, two Br atoms and the central N
      atom of the dpa ligand lying on the mirror plane. The dpa ligand is not planar,
      showing a dihedral angle of 34.7 (2) degrees  between the pyridine rings. The
      complex mol-ecules are connected by inter-molecular N-H?Br hydrogen bonds,
      forming chains along [001]. Inter-molecular C-H?Br hydrogen bonds and pi-pi inter
      actions between the pyridine rings [centroid-centroid distance = 3.667 (4) A] are
      also observed.

PMID- 22969445
TI  - catena-Poly[triethyl-ammonium [[tetra-MU-acetato-kappa(8)O:O'-dicuprate(II)]-MU
      acetato-kappa(2)O:O'] tetra-hydro-furan monosolvate].
AB  - In the title compound, {[(C(2)H(5))(3)NH][Cu(2)(CH(3)COO)(5)].C(4)H(8)O}(n), the
      two different Cu(II) atoms are coordinated in a pseudo-square-pyramidal
      environment by five O atoms from the acetate ligands. Neighbouring pairs of
      Cu(II) atoms are linked by four basally coordinating bridging acetate ligands as
      in the crystal structure of copper acetate monohydrate. The fifth, apically
      coordinating ligand links two of the dicopper tetra-acetate paddlewheel-units
      together, thus building a linear coordination polymer which extends along [10-1].
      Each apical acetate ligand is linked by an N-H?O hydrogen bond to a triethyl
      ammonium cation. Weak C-H?O hydrogen bonding interactions also occur.

PMID- 22969446
TI  - Dibromido(6,6'-dimethyl-2,2'-bipyridine-kappa(2)N,N')cadmium.
AB  - In the title compound, [CdBr(2)(C(12)H(12)N(2))], the Cd(II) atom is four
      coordinated in a distorted tetra-hedral geometry by two N atoms from a 6,6'
      dimethyl-2,2'-bipyridine ligand and two terminal Br atoms. In the crystal, C-H?Br
      hydrogen bonds and pi-pi stacking inter-actions between the pyridine rings
      [centroid-centroid distance = 3.763 (5) A] are present.

PMID- 22969447
TI  - (Di-2-pyridyl-amine-kappa(2)N(2),N(2'))diiodidopalladium(II).
AB  - The Pd(II) ion in the title complex, [PdI(2)(C(10)H(9)N(3))], is four-coordinated
      in a distorted square-planar environment defined by the two pyridine N atoms of
      the chelating di-2-pyridyl-amine (dpa) ligand and two I(-) anions. The dpa ligand
      is not planar, the dihedral angle between the pyridine rings being 51.2 (2)
      degrees . In the crystal, pairs of complex mol-ecules are assembled through inter
      molecular N-H?I hydrogen bonds into dimeric species. The complexes are stacked in
      columns along the b axis and display several inter-molecular pi-pi inter-actions
      between the pyridine rings, with a shortest ring centroid-centroid distance of
      3.957 (3) A.

PMID- 22969448
TI  - Bis(di-2-pyridyl-amine-kappa(2)N(2),N(2'))palladium(II) bis-(thio-cyanate).
AB  - The Pd(II) atom of the title salt, [Pd(C(10)H(9)N(3))(2)](NCS)(2), lies on a
      center of inversion and exists in a square-planar environment defined by the four
      pyridine N atoms derived from the two chelating di-2-pyridyl-amine (dpa) ligands.
      The chelate ring displays a boat conformation with a dihedral angle between the
      pyridine rings of 43.0 (1) degrees . Adjacent thio-cyanate ions are linked to the
      cations by N-H?N hydrogen bonds.

PMID- 22969449
TI  - Poly[[diaqua-bis-(MU-oxalato-kappa(4)O(1),O(2):O(1'),O(2'))bis-(MU(3)-5
      oxidopyridin-1-ium-3-carboxyl-ato-kappa(3)O(3):O(3'):O(5))diholmium(III)]
      dihydrate].
AB  - In the title compound,
      {[Ho(2)(C(6)H(4)NO(3))(2)(C(2)O(4))(2)(H(2)O)(2)].2H(2)O}(n), the Ho(III) atom is
      coordinated by three O atoms from three 5-hy-droxy-nicotinate ligands, four O
      atoms from two oxalate ligands, each lying on an inversion center, and one water
      mol-ecule in a distorted square-anti-prismatic geometry. The 5-hy-droxy
      nicotinate ligand is protonated at the N atom and deprotonated at the hy-droxy
      group. The Ho(III) atoms are bridged by the carboxyl-ate and phenolate O atoms,
      forming a three-dimensional framework. N-H?O and O-H?O hydrogen bonds, as well as
      pi-pi inter-actions between the pyridine rings [centroid-centroid distance =
      3.794 (2) A], are observed.

PMID- 22969450
TI  - catena-Poly[[[(1,10-phenanthroline-kappa(2)N,N')praseodymium(III)]-di-MU-4
      hydroxy-benzoato-kappa(4)O(1):O(1')-MU-nitrato-kappa(3)O,O':O] bis-(1,10
      phenanthroline)].
AB  - The title complex, [Pr(C(7)H(5)O(3))(2)(NO(3))(C(12)H(8)N(2))].2C(12)H(8)N(2),
      has a polymeric chain structure, with two uncoordinated 1,10-phenanthroline mol
      ecules in the lattice. The Pr(III) centre has a monocapped square-anti-prismatic
      coordination geometry, comprised of two N atoms from one chelating 1,10
      phenanthroline ligand, four carboxyl-ate O atoms from four 4-hy-droxy-benzoate
      anions and three O atoms from two nitrate anions. The 4-hy-droxy-benzoate and
      nitrate anions function as MU(2)-bridging ligands and link the Pr(III) ions into
      a one-dimensional chain structure along the c axis. Inter-molecular O-H?N
      hydrogen bonds are observed between the 4-hy-droxy-benzoate anions and the
      uncoordinated 1,10-phenanthroline mol-ecules.

PMID- 22969451
TI  - Diaqua-bis-(1H-imidazole-kappaN(3))bis-(4-nitro-benzoato-kappaO(1))cadmium.
AB  - In the centrosymmetric title compound,
      [Cd(C(7)H(4)NO(4))(2)(C(3)H(4)N(2))(2)(H(2)O)(2)], the Cd(II) atom, located on an
      inversion center, is coordinated by two N atoms and four O atoms in an octa
      hedral geometry. The inter-nal cohesion of the mol-ecule is enhanced by an intra
      molecular O-H?O hydrogen bond. Inter-molecular O-H?O and C-H?O hydrogen bonds and
      pi-pi contacts [centroid-centroid distance = 3.6549 (2) A] define two-dimensional
      networks parallel to (001), which are further connected by weaker C-H?O inter
      actions into a weakly connected three-dimensional supra-molecular framework.

PMID- 22969452
TI  - Poly[[diaqua-(MU(8)-benzene-1,2,4,5-tetra-carboxyl-ato)calciumzinc] monohydrate].
AB  - In the title complex, {[CaZn(C(10)H(2)O(8))(H(2)O)(2)].H(2)O}(n), the Zn(II) ion
      is coordinated by four O atoms from four benzene-1,2,4,5-tetra-carboxyl-ate
      anions in a distorted tetra-hedral geometry. The Ca(II) ion is eight-coordinated
      by six O atoms from four benzene-1,2,4,5-tetra-carboxyl-ate anions and by two
      water mol-ecules in a distorted square-anti-prismatic geometry. The Ca(II) and
      Zn(II) ions and the lattice water mol-ecule are located on twofold rotation axes;
      the centroid of the benzene-1,2,4,5-tetra-carboxyl-ate anion is located on a
      centre of inversion. The MU(8)-bridging mode of the anion results in the
      formation of a three-dimensional structure with channels extending along [100] in
      which lattice water mol-ecules are situated. Inter-molecular O-H?O hydrogen bonds
      involving the coordinating and lattice water mol-ecules as donors and the
      carboxyl-ate O atoms and lattice water mol-ecules as acceptors are present in the
      structure.

PMID- 22969454
TI  - Dichloridobis(4-fluoro-aniline-kappaN)zinc.
AB  - In the title compound, [ZnCl(2)(C(6)H(6)FN)(2)], the Zn(II) atom has a slightly
      distorted tetra-hedral geometry, being coordinated by the N atoms of two 4-fluoro
      aniline mol-ecules and the two Cl(-) anions. The two benzene rings are almost
      perpendicular to one another, making a dihedral angle of 89.96 (13) degrees . In
      the crystal, mol-ecules are linked via pairs of N-H?Cl hydrogen bonds, forming
      chains propagating along the b axis. These chains are in turn linked via a second
      pair of N-H?Cl hydrogen bonds, forming a two-dimensional network parallel to the
      ab plane. The title compound crystallizes in the space group Pca2(1) and exhibits
      weak second harmonic generation (SHG) properties.

PMID- 22969453
TI  - Bis[1-(eth-oxy-carbonyl-meth-yl)pyridinium] bis-(1,2-dicyano-ethene-1,2-dithiol
      ato-kappa(2)S,S')nickelate(II).
AB  - The asymmetric unit of the title ion-pair complex,
      (C(9)H(12)NO(2))(2)[Ni(C(4)N(2)S(2))(2)], contains two 1-(eth-oxy-carbonyl-meth
      yl)pyridinium cations and one bis-(1,2-dicyano-ethene-1,2-dithiol
      ato)nickelate(II) dianion, which exhibits a slightly distorted square-planar
      coordination geometry. In the crystal, the cations are linked by strong C-H?O
      hydrogen bonds into C(6) chains along [100]. The cations and anions are linked
      into a three-dimensional architecture by weak C-H?N and C-H?S inter-actions.

PMID- 22969455
TI  - [MU-N,N'-Bis(2-amino-eth-yl)ethane-1,2-diamine-kappa(4)N(1),N(1'):N(2),N(2')]bis
      {[N,N'-bis-(2-amino-eth-yl)ethane-1,2-diamine-kappa(4)N,N',N'',N''']cadmium}
      tetra-kis-(perchlorate).
AB  - The centrosymmetric dinuclear cadmium title complex,
      [Cd(2)(C(6)H(18)N(4))(3)](ClO(4))(4), was obtained by the reaction of N,N'-bis-(2
      amino-eth-yl)ethane-1,2-diamine (trien) with Cd(NO(3))(2).4H(2)O and sodium
      perchlorate in methanol. The Cd(II) cation is coordinated by four N atoms of a
      non-bridging trien ligand and by two N atoms of a bridging trien ligand in a
      slightly distorted octa-hedral coordination geometry. The bridging ligand shares
      another two N atoms with a neighboring symmetry-equivalent Cd(II) cation. The
      structure displays C-H?O and N-H?O hydrogen bonding. The perchlorate anion is
      disordered over two sets of sites in a 0.854 (7): 0.146 (7) ratio.

PMID- 22969456
TI  - (Ethyl-enediamine-kappa(2)N,N)bis[2-(pyridin-2-yl-kappaN)-1,3-imidazol-1-ido
      kappaN(1)]cobalt(III) nitrate monohydrate.
AB  - In the title compound, [Co(C(8)H(6)N(3))(2)(C(2)H(8)N(2))]NO(3).H(2)O, the
      Co(III) ion is coordinated by four N atoms from two 2-(pyridin-2-yl)-1,3-imidazol
      1-ide ligands and two N atoms of ethyl-enediamine in a distorted octa-hedral
      geometry. In the crystal, classical N-H?N(O) and O-H?N(O) hydrogen bonds connect
      all the isolated components together to yield a three-dimensional structure.

PMID- 22969457
TI  - Bis(2,2'-bipyridine-kappa(2)N,N')(3-methyl-benzoato-kappa(2)O,O')zinc 3-methyl
      benzo-ate-3-methyl-benzoic acid-water (1/1/2).
AB  - The title compound,
      [Zn(C(8)H(7)O(2))(C(10)H(8)N(2))(2)](C(8)H(7)O(2)).C(8)H(8)O(2).2H(2)O, is
      comprised of a Zn(2+) cation, two 2,2'-bipydine (bipy) ligands and one 3-methyl
      benzoate anion (L(-)) together with one uncoordinating L(-) anion, one
      uncoordinating HL mol-ecule and two lattice water mol-ecules. The Zn(II) atom is
      coordinated by four N atoms of two bipy ligands and two O atoms from one L(-)
      ligand in a distorted octa-hedral geometry. Pairs of centrosymmetrically related
      complex mol-ecules form dimers via slipped pi-stacking inter-actions between bipy
      ligands with an inter-planar distance of 3.470 (4) A. The dimers are linked into
      supra-molecular chains along [111], via C-H?O hydrogen bonds. The uncoordinated
      L(-) anions, HL mol-ecules and water mol-ecules are connected with each other via
      O-H?O hydrogen bonds, forming chains between the metal complex chains and binding
      them together via C-H?O contacts. The resulting layers parallel to (010) are
      further assembled into a three-dimensional supra-molecular architecture through
      additional C-H?O inter-actions.

PMID- 22969458
TI  - trans-Acetyl-dicarbon-yl(eta(5)-cyclo-penta-dien-yl)(methyl-diphenyl
      phosphane)molybdenum(II).
AB  - The title compound, [Mo(C(5)H(5))(C(2)H(3)O)(C(13)H(13)P)(CO)(2)], was prepared
      by reaction of [Mo(CH(3))(C(5)H(5))(CO)(3)] with methyl-diphenyl-phosphane. The
      Mo(II) atom exhibits a four-legged piano-stool coordination geometry with the
      acetyl and phosphane ligands trans to each other. There are several inter
      molecular C-H?O hydrogen-bonding inter-actions involving carbonyl and acetyl O
      atoms as acceptors. A close nearly parallel pi-pi inter-action between the cyclo
      penta-dienyl plane and the phenyl ring of the phosphane ligand is present, with
      an angle of 6.4 (1) degrees  between the two least-squares planes. The centroid
      to-centroid distance between these groups is 3.772 (3) A, and the closest
      distance between two atoms of these groups is 3.449 (4) A. Since each Mo complex
      is engaged in two of these inter-actions, the complexes form an infinite pi-stack
      coincident with the a axis.

PMID- 22969459
TI  - Bis(4-amino-pyridinium) tetra-iodido-cad-mate monohydrate.
AB  - The title compound, (C(5)H(7)N(2))(2)[CdI(4)].H(2)O, contains one [CdI(4)](2-)
      anion, two prontonated 4-amino-pyridine mol-ecules and one water mol-ecule in the
      asymmetric unit. In the anion, the Cd(II) atom is coordinated by four I atoms in
      a slightly distorted tetra-hedral geometry. The [CdI(4)](2-) anion and the water
      mol-ecule are bis-ected by a crystallographic mirror plane perpendicular to the c
      axis direction, with the Cd(II) atom, two of the I atoms and the atoms of the
      water mol-ecule located on this plane. The crystal packing is stabilized by inter
      molecular N-H?I, N-H?O and O-H?I hydrogen bonds and by pi-pi stacking inter
      actions [centroid-centroid distance = 3.798 (3) A) between pyridine rings, which
      build up a three-dimensional network.

PMID- 22969460
TI  - Diaqua-bis-(2-iodo-benzoato-kappaO)bis-(nicotinamide-kappaN(1))copper(II).
AB  - In the title complex, [Cu(C(7)H(4)IO(2))(2)(C(6)H(6)N(2)O)(2)(H(2)O)(2)], the
      Cu(II) cation is located on an inversion center and is coordinated by two
      monodentate 2-iodo-benzoate (IB) anions, two nicotinamide (NA) ligands and two
      water mol-ecules in a distorted octa-hedral coordination geometry. The dihedral
      angle between the carboxyl-ate group and the adjacent benzene ring is 32.12 (14)
      degrees , while the pyridine ring and the benzene ring are oriented at a dihedral
      angle of 82.02 (5) degrees . The coordinating water mol-ecule links with the
      carboxyl-ate group via an intra-molecular O-H?O hydrogen bond. In the crystal, N
      H?O, O-H?O and weak C-H?O hydrogen bonds link the mol-ecules into a three
      dimensional supra-molecular network.

PMID- 22969461
TI  - [MU-(3,4,5,6,7-eta:1,9,10,11,12)-5,11-Di-tert-butyl-2,2,8,8-tetra-methyl-2,8
      disila-tricyclo-[7.3.0.0(3,7)]dodeca-tetra-enedi-yl]bis-[dicarbonyl
      ruthenium(I)].
AB  - The title compound, [Ru(2)(C(22)H(34)Si(2))(CO)(4)], contains two Ru(I) atoms
      linked by a bridging (eta(5)-(t)BuC(5)H(2))(2)(SiMe(2))(2) ligand ((t)Bu is a
      tert-butyl and Me is a methyl group) with an Ru-Ru bond length of 2.8401 (7) A.
      The dihedral angle between the planes of the cyclo-penta-dienyl rings of the
      ligand is 123.13 (19) degrees . The four terminal carbonyl ligands are bound in a
      symmetrical and staggered array. In the crystal, mol-ecules are linked via pairs
      of C-H?O hydrogen bonds, forming inversion dimers.

PMID- 22969462
TI  - Bis(2-hy-droxy-imino-methyl-6-meth-oxy-phenolato-kappa(2)N,O(1))copper(II).
AB  - In the title compound, [Cu(C(8)H(8)NO(3))(2)], the nearly planar mol-ecule
      (r.m.s. deviation = 0.037 A) is centrosymmetric with the Cu(II) atom lying on an
      inversion center. The Cu(II) atom is tetra-coordinated, displaying a slightly
      distorted square-planar geometry. The main deviation from the ideal geometry is
      seen in the differences in the Cu-O [1.8833 (10) A] and Cu-N [1.9405 (13) A] bond
      lengths, while angular deviations are less than 3 degrees . Intra-molecular O-H?O
      and inter-molecular Csp(2)-H?O hydrogen bonds form S(5) and R(2) (2)(8) ring
      motifs, respectively. The latter inter-action results in chains of mol-ecules
      along [100].

PMID- 22969463
TI  - Di-MU-chlorido-MU-(dimethyl sulfide)-bis-{dichlorido[(dimethyl selenide
      kappaSe)(dimethyl sulfide-kappaS)(0.65/0.35)]niobium(III)}(Nb-Nb).
AB  - The dinuclear compound, [Nb(2)Cl(6)(C(2)H(6)S)(1.7)(C(2)H(6)Se)(1.3)], features
      an Nb(III)=Nb(III) double bond [2.6878 (5) A]. The mol-ecule lies on a twofold
      rotation axis that passes through the middle of this bond as well as through the
      bridging dimethyl sulfide ligand. The Nb(III) ion exists in an octa-hedral
      coordination environment defined by two terminal and two bridging Cl atoms, and
      (CH(3))(2)Se/(CH(3))(2)S ligands. The (bridging) ligand lying on the twofold
      rotation axis is an ordered (CH(3))(2)S ligand, whereas the terminal ones on a
      general position are a mixture of (CH(3))(2)Se and (CH(3))(2)S ligands in a 0.647
      (2):0.353 (2) ratio (the methyl C atoms are also disordered).

PMID- 22969464
TI  - Bis[MU-N-(tert-butyl-dimethyl-silyl)-N-(pyridin-2-ylmeth-yl)amido]-bis-[methyl
      cobalt(II)].
AB  - The green title complex, [Co(2)(CH(3))(2)(C(12)H(21)N(2)Si)(2)], was obtained
      from bis-{[MU-N-tert-butyl-dimethyl-silyl-N-(pyridin-2-ylmeth-yl)amido]
      chloridocobalt(II)} and methyl-lithium in diethyl ether at 195 K via a metathesis
      reaction. The dimeric cobalt(II) complex exhibits a crystallographic center of
      inversion in the middle of the Co(2)N(2) ring (average Co-N = 2.050 A). The
      Co(II) atom shows a distorted tetra-hedral coordination sphere. The exocyclic Co
      N bond length to the pyridyl group shows a similar value of 2.045 (4) A. The
      exocyclic methyl group has a rather long Co-C bond length of 2.019 (5) A.

PMID- 22969465
TI  - cis-Dibromidobis(2-phenyl-pyridine-kappaN)platinum(II).
AB  - In the title complex, [PtBr(2)(C(11)H(9)N)(2)], the Pt(II) ion has a distorted
      cis-Br(2)N(2) square-planar coordination geometry defined by two N atoms from two
      2-phenyl-pyridine (ppy) ligands and two Br(-) anions. The ppy ligands are not
      planar, the dihedral angles between the pyridine and benzene rings being 49.0 (3)
      and 47.3 (3) degrees . In the crystal, the complex mol-ecules are stacked in
      columns along the a axis. In the columns, there are numerous intra- and inter
      molecular pi-pi inter-actions between the six-membered rings, the shortest ring
      centroid-centroid distance being 3.774 (6) A.

PMID- 22969466
TI  - Tetra-kis[MU-1,3-bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene-kappa(2)N:N']tris
      ilver(I) tris-(hexa-fluoridophosphate).
AB  - In the title compound, [Ag(3)(C(12)H(12)N(2)O(2))(4)](PF(6))(3), one Ag(I) ion,
      lying on a twofold rotation axis, is coordinated by four N atoms from four 1,3
      bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene (L) ligands in a distorted tetra-hedral
      geometry and the other Ag(I) ion is coordinated by two N atoms from two L ligands
      in a bent arrangement [N-Ag-N = 169.03 (17) degrees ]. Two L ligands adopt a syn
      conformation, while the other two adopt an anti conformation. They bridge
      adjacent Ag(I) ions, forming a trinuclear complex. One of the PF(6) (-) anions is
      half-occupied, with the P atom located on a twofold rotation axis. The PF(6) (-)
      anions link the complex mol-ecules via Ag?F inter-actions [2.80 (2) and 2.85 (2)
      A] into a polymeric chain along [100].

PMID- 22969467
TI  - catena-Poly[[silver(I)-MU-2-[(pyrazin-2-yl-kappa(2)N(1):N(4))amino-meth
      yl]phenol] nitrate].
AB  - The Ag(I) atom in the polycationic salt, {[Ag(C(11)H(11)N(3)O)]NO(3)}(n), shows a
      linear coordination [N-Ag-N = 175.0 (2) degrees ]; the polymeric nature arises
      from bridging by the pyrazine portion of the ligand, resulting in chains
      extending parallel to [100]. The NO(3) (-) counter-ions surround the polymeric
      chain and inter-act only weakly with it [Ag?O = 2.701 (4) and 2.810 (5) A].
      Adjacent chains are linked into a three-dimensional network by O-H?O and N-H?O
      hydrogen bonds.

PMID- 22969468
TI  - {4,4'-Dimethyl-2,2'-[2,2-dimethyl-propane-1,3-diylbis(nitrilo-methanylyl
      idene)]diphenolato}copper(II) monohydrate.
AB  - The asymmetric unit of the title compound, [Cu(C(21)H(24)N(2)O(2))].H(2)O,
      comprises half of a Schiff base complex and half of a water mol-ecule. The whole
      compound is generated by crystallographic twofold rotation symmetry. The geometry
      around the Cu(II) atom, located on a twofold axis, is distorted square-planar,
      which is supported by the N(2)O(2) donor atoms of the coordinating Schiff base
      ligand. The dihedral angle between the symmetry-related benzene rings is 47.5 (4)
      degrees . In the crystal, the water mol-ecule that is hydrogen bonded to the
      coordinated O atoms links the mol-ecules via O-H?O inter-actions into chains
      parallel to [001]. The crystal structure is further stabilized by C-H?pi inter
      actions, and by pi-pi inter-actions involving inversion-related chelate rings
      [centroid-centroid distance = 3.480 (4) A].

PMID- 22969469
TI  - catena-Poly[[[(5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane
      kappa(4)N)nickel(II)]-MU-oxido-[dioxidotungstate(VI)]-MU-oxido] tetra-hydrate].
AB  - In the title compound, {[NiWO(4)(C(16)H(36)N(4))].4H(2)O}(n), the Ni(II) ion lies
      on an inversion center and is octahedrally coordinated by four N atoms of the
      tetradentate macrocyclic 5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo
      tetra-decane (L) ligand in the equatorial plane and two O atoms of [WO(4)](2-)
      anions in axial positions. Each [WO(4)](2-) anion bridges two adjacent [NiL](2+)
      cations, forming a chain along [001]. The chains are further connected via N-H?O,
      O-H?O and C-H?O hydrogen-bonding inter-actions, generating a three-dimensional
      structure.

PMID- 22969470
TI  - 2,2'-[(1E,2E)-1,2-Bis(hy-droxy-imino)-ethane-1,2-di-yl]dipyridinium hexa
      chloridorhenate(IV).
AB  - The title salt, (C(12)H(12)N(4)O(2))[ReCl(6)], consists of 2,2'-[(1E,2E)-1,2-bis
      (hy-droxy-imino)-ethane-1,2-di-yl]dipyridinium cations and [ReCl(6)](2-) anions
      which are both located on inversion centres. Each cation consists of a glyoxime
      moiety attached to two protonated pyridine rings in ortho positions. In the
      crystal, E,E isomers of the cation are observed which differ in the spatial
      arrangement of the pyridine rings. These rings are positionally disordered over
      two positions with site-occupancy factors of 0.786 (7) and 0.214 (7). The
      geometry of the cation is compared with that of a recently reported dipyridyl
      glyoxime with the same configuration. The cations and anions are involved in a
      network of inter-molecular O-H?Cl, N-H?Cl and C-H?Cl hydrogen bonds.

PMID- 22969471
TI  - catena-Poly[[[{1-[(E)-phenyl(pyridin-2-yl-kappaN)methylidene]semicarbazidato
      kappa(2)N(1),O}copper(II)]-MU-dicyanamido-kappa(2)N(1):N(5)] monohydrate].
AB  - The Cu(II) atoms in the title coordination polymer,
      {[Cu(C(13)H(11)N(4)O)(C(2)N(3))].H(2)O}(n), are N,N',O-chelated by the
      deprotonated Schiff base ligands, and adjacent metal atoms are bridged by the
      dicyanamide ions, generating a polymeric chain that propagates along the b axis.
      The two independent metal atoms show a square-pyramidal N(4)O coordination. The
      two independent water mol-ecules are disordered over two positions; each water
      mol-ecule is a hydrogen-bond donor to a carbonyl O atom. Weak N-H?N hydrogen
      bonding is also observed.

PMID- 22969472
TI  - catena-Poly[disilver(I)(Ag-Ag)-bis-(MU(3)-quinoline-3-carboxyl-ato)
      1:2:1'kappa(3)O:O':N;2:1'':2''kappa(3)N:O:O'].
AB  - In the title compound, [Ag(2)(C(10)H(6)NO(2))(2)](n), the Ag(I) atom is
      coordinated by one N atom and two O atoms from three quinoline-3-carboxyl-ate
      ligands in a T-shaped fashion, with an additional Ag?Ag distance of 2.9468 (6) A.
      The ligands connect the Ag(I) atoms into a double-chain structure along [010].
      Weak Ag?O inter-actions [Ag?O = 2.802 (3) and 2.877 (4) A] link the double-chains
      into a layer network parallel to (101). pi-pi inter-actions are also observed in
      the layer network [centroid-centroid distances = 3.780 (3) and 3.777 (3) A].

PMID- 22969473
TI  - Poly[[diaqua-bis-[MU-2-(4-fluoro-phen-oxy)acetato-kappa(2)O(1):O(1')]magnesium]
      0.4-hydrate].
AB  - In the title compound, {[Mg(C(8)H(6)FO(3))(2)(H(2)O)(2)].0.4H(2)O}(n), slightly
      distorted octa-hedral MgO(6) complex units have crystallographic inversion
      symmetry, the coordination polyhedron comprising two trans-related water mol
      ecules and four carboxyl O-atom donors, two of which are bridging. Within the two
      dimensional complex polymer which is parallel to (100), coordinating water mol
      ecules form inter-molecular O-H?O hydrogen bonds with carboxyl-ate and phen-oxy O
      atom acceptors, as well as with the partial-occupancy solvent water mol-ecules.

PMID- 22969474
TI  - Dichloridobis{1-[(2-methyl-benzimidazol-1-yl-kappaN(3))meth
      yl]benzotriazole}zinc.
AB  - The title mononuclear Zn(II) complex, [ZnCl(2)(C(15)H(13)N(5))(2)], is isotypic
      with the previously reported Hg(II) complex. The Zn(II) atom is located on a
      twofold rotation axis and has a distorted tetra-hedral environment of two Cl
      atoms and two N atoms from two heterocyclic ligands. In the crystal, complex mol
      ecules are extended by inter-molecular pi-pi inter-actions [centroid-centroid
      distance = 3.792 (2) A] into a three-dimensional supra-molecular network.

PMID- 22969476
TI  - Dichlorido(1-{(E)-[phen-yl(pyridin-2-yl-kappaN)methyl-idene]amino
      kappaN}pyrrolidin-2-one-kappaO)copper(II) monohydrate.
AB  - The Cu(II) atom in the title compound, [CuCl(2)(C(16)H(15)N(3)O)].H(2)O, is
      N,N',O-chelated by the neutral Schiff base ligand and exists in a square
      pyramidal geometry. It is displaced by 0.316 (1) A out of the square plane
      (r.m.s. deviation = 0.015 A) in the direction of the apical Cl atom. The apical
      Cl atoms of adjacent complex units are hydrogen-bond acceptors to two water mol
      ecules, the inter-action generating a centrosymmetric dimer through a cyclic R(4)
      (2)(8) association.

PMID- 22969475
TI  - (Cyanato-kappaN){1-[(E)-phen-yl(pyridin-2-yl-kappaN)methyl-idene]semicarbazidato
      kappa(2)N(1),O}copper(II).
AB  - The Cu(II) atom in the title compound, [Cu(C(13)H(11)N(4)O)(NCO)], is N,N',O
      chelated by the mono-deprotonated Schiff base ligand and it is also covalently
      bonded to the nitro-gen end of the cyanate ion. The Cu(II) atom shows a square
      planar coordination that is distorted towards square-pyramidal owing to an inter
      molecular Cu?N(cyanate) inter-action [2.623 (2) A], which gives a centrosymmetric
      dimer. In the square-planar description, the Cu(II) atom is displaced out of the
      square plane [r.m.s. deviation = 0.048 A] by 0.084 (1) A in the direction of the
      apical occupant. In the crystal, adjacent complex dimers are linked by an amine N
      H?N hydrogen-bond pair, also giving a centrosymmetric cyclic association [graph
      set R(2) (2)(8)], generating a linear chain parallel to [110].

PMID- 22969477
TI  - Diaqua-bis-{3-[4-(1H-imidazol-1-yl)phenyl]-5-(pyridin-2-yl-kappaN)-1H-1,2,4
      triazol-1-ido-kappaN(1)}zinc.
AB  - The centrosymmetric mol-ecule of the title compound,
      [Zn(C(16)H(11)N(6))(2)(H(2)O)(2)], contains one Zn(2+) ion located on a center of
      symmetry, two 3-[4-(1H-imidazol-1-yl)phen-yl]-5-(pyridin-2-yl)-1H-1,2,4-triazol-1
      ide (Ippyt) ligands and two coordinating water mol-ecules. The Zn(II) ion is six
      coordinated in a distorted octa-hedral coordination geometry by four N atoms from
      two Ippyt ligands and by two O atoms from two water mol-ecules. Adjacent units
      are inter-connected though O-H?N hydrogen bonds, forming a three-dimensional
      network.

PMID- 22969478
TI  - Poly[diaqua-(MU(4)-2,5-dicarb-oxy-benzene-1,4-dicarboxyl-ato
      kappa(4)O(1):O(2):O(4):O(5))(MU(2)-2,5-dicarb-oxy-benzene-1,4-dicarboxyl-ato
      kappa(2)O(1):O(4))bis-(1,10-phenanthroline-kappa(2)N,N')dimanganese(II)].
AB  - In the title compound, [Mn(2)(C(10)H(4)O(8))(2)(C(12)H(8)N(2))(2)(H(2)O)(2)](n),
      the Mn(2+) ion has a slightly distorted octa-hedral N(2)O(4) coordination
      geometry being coordinated by one aqua O atom, two N atoms of the chelating 1,10
      phenanthroline ligand and three carboxyl O atoms from three 2,5-dicarb-oxy
      benzene-1,4-dicarboxyl-ate (H(2)btec(2-)) ligands. The H(2)btec(2-) anion
      exhibits two different coordination modes, viz. MU(2) and MU(4). Both of the
      H(2)btec(2-) anions are located on special positions (inversion centers). The
      MU(4)-anion bridges adjacent Mn(II) atoms, forming a chain along the a axis.
      Adjacent chains are further bridged by MU(2)-anions, resulting in a two
      dimensional layered polymer parallel to (011). In the crystal, extensive carb-oxy
      carboxyl-ate O-H?O and water-carboxyl-ate O-H?O inter-actions lead to the
      formation of a three-dimensional supra-molecular network.

PMID- 22969479
TI  - Tetra-butyl-ammonium tetra-kis-(trimethyl-silanolato-kappaO)ferrate(III).
AB  - In the title salt, (C(16)H(36)N)[Fe(C(3)H(9)OSi)(4)], the cation contains a
      central N atom bonded to four n-butyl alkyl groups in a tetra-hedral arrangement,
      while the anion contains a central Fe(III) atom tetra-hedrally coordinated by
      four trimethyl-silanolate ligands.

PMID- 22969480
TI  - Tricarbonylbis-(triphenyl-phosphane-kappaP)iridium(I) hexa-fluoridophosphate
      methanol monosolvate.
AB  - In the title compound, [Ir(C(18)H(15)P)(2)(CO)(3)]PF(6).CH(3)OH, the Ir(I) atom
      is coordinated by two triphenyl-phosphine ligands in axial sites and three
      carbonyl ligands in the equatorial plane of a fairly regular trigonal bipyramid:
      the equatorial C-Ir-C angles range from 115.45 (9) to 126.42 (10) degrees . The
      small deviations from the ideal tetra-hedral geometry around the P atoms are
      illustrated by C-P-C angles ranging from 104.08 (9) to 106.46 (9) degrees . In
      the crystal, the mol-ecules are linked by weak C-H?F, C-H?O and C-H?pi inter
      actions.

PMID- 22969481
TI  - Trichlorido(4,4'-dimethyl-2,2'-bipyridine-kappa(2)N,N')(methanol
      kappaO)indium(III) methanol monosolvate.
AB  - In the title compound, [InCl(3)(C(12)H(12)N(2))(CH(3)OH)].CH(3)OH, the In(III)
      atom is six-coordinated in a distorted octa-hedral geometry by two N atoms from a
      chelating 4,4'-dimethyl-2,2'-bipyridine ligand, one O atom from a methanol mol
      ecule and three Cl atoms. In the crystal, inter-molecular O-H?O and O-H?Cl
      hydrogen bonds link the complex and solvent methanol mol-ecules. Intra-molecular
      C-H?Cl hydrogen bonds are also present in the complex.

PMID- 22969482
TI  - [5,15-Bis(2-methyl-prop-yl)porphyrinato]nickel(II).
AB  - The title compound, [Ni(C(28)H(28)N(4))], crystallizes with two independent mol
      ecules in the unit cell, one of which is located on an inversion center. Both
      macrocycles exhibit a planar conformation with average deviation from the least
      squares-plane of the 24 macrocycle atoms of Delta24 = 0.043 A for the first mol
      ecule and 0.026 A for the mol-ecule located on an inversion center. The average
      Ni-N bond lengths are 1.955 (2) and 1.956 (2) A in the two mol-ecules. The mol
      ecules form pi-pi dimers of inter-mediary strength with a mean plane separation
      of 3.36 (2) A.

PMID- 22969483
TI  - trans-Dichloridotetra-pyrazine-ruthenium(II) dichloro-methane disolvate.
AB  - In the title compound, [RuCl(2)(C(4)H(4)N(2))(4)].2CH(2)Cl(2), the Ru(II) atom
      occupies a position of 222 symmetry and the C atom of the solvent mol-ecule
      occupies a site with twofold symmetry. The Ru(II) atom has a slightly distorted
      octa-hedral geometry. The pyrazine rings are propeller-like and rotated 45.1 (1)
      degrees  from the RuN(4) plane. In the crystal, the complex and solvent mol
      ecules are bridged by weak C-H?N hydrogen bonds along the c axis. Weak inter
      molecular C-H?Cl contacts link the complexes in the ab plane, forming a network.

PMID- 22969484
TI  - {2-[(2-Carbamoylhydrazin-1-yl-idene)methyl-kappa(2)N(1),O]-5-meth-oxy-phenolato
      kappaO(1)}chloridocopper(II).
AB  - The asymmetric unit of the title compound, [Cu(C(9)H(10)N(3)O(3))Cl], contains
      two independent mol-ecules with similar structures. The Cu(II) cation is N,O,O'
      chelated by the deprotonated Schiff base ligand and is further coordinated by a
      Cl(-) anion in a distorted ClNO(2) square-planar geometry. In the crystal,
      adjacent mol-ecules are linked by N-H?O and N-H?Cl hydrogen bonds, forming a two
      dimensional network parallel to [100].

PMID- 22969485
TI  - Di-MU-azido-kappa(4)N(1):N(1')-bis-({1-[(E)-phen-yl(pyridin-2-yl-kappaN)methyl
      idene]thio-semi-carbazidato-kappa(2)N(1),S}copper(II)).
AB  - In the title compound, [Cu(2)(C(13)H(11)N(4)S)(2)(N(3))(2)], the Cu(II) cation is
      N,N',S-chelated by the deprotonated Schiff base ligand and is coordinated by the
      azide anion, while an N atom from an adjacent azide anion bridges the Cu(II)
      cation at the apical position with a longer Cu-N distance of 2.533 (3) A,
      completing the distorted N(4)S square-pyramidal coordination geometry. A pair of
      azide anions bridge the two Cu(II) cations, forming a centrosymmetric binuclear
      mol-ecule. In the crystal, the binuclear mol-ecules are linked by an N-H?N
      hydrogen bond into a ribbon running along the a axis.

PMID- 22969486
TI  - Poly[(MU(5)-2,2'-bipyridine-5,5'-dicarboxyl-ato)lead(II)].
AB  - In the title polymeric compound, [Pb(C(12)H(6)N(2)O(4))](n), the Pb(II) cation,
      located on a mirror plane, is N,N'-chelated by a 2-2'-bipyridine-5,5'-dicarboxyl
      ate (bpdc) anion and is further coordinated by six O atoms from four carboxyl
      groups of bpdc anions in an irregular N(2)O(6) geometry. The carboxylate groups
      bridge the Pb(II) cations, forming a three-dimensional polymeric structure. The
      carboxyl-ate group is twisted away from the attached pyridine ring by 11.4 (3)
      degrees .

PMID- 22969487
TI  - Dimorpholinium tetra-chlorido-cobaltate(II).
AB  - In the title mol-ecular salt, (C(4)H(10)NO)(2)[CoCl(4)], the morpholinium cations
      adopt chair conformations and the tetra-chloridocobaltate(II) anion is
      significantly distorted from regular tetra-hedral geometry [Cl-Co-Cl = 102.183
      (19)-117.59 (2) degrees ]. The Co-Cl bond lengths for the chloride ions not
      accepting hydrogen bonds are significantly shorter than those for the chloride
      ions accepting such bonds. In the crystal, the components are linked by N-H?O and
      N-H?Cl and bifurcated N-H?(O,Cl) hydrogen bonds to generate (100) sheets.

PMID- 22969488
TI  - Triaqua[2,2'-(propane-1,3-diyl)bis(5-carboxy-1H-imidazole-4-carboxylato
      kappa(2)N(3),O(4))]calcium(II) tetrahydrate.
AB  - In the title compound, [Ca(C(13)H(10)N(4)O(8))(H(2)O)(3)].4H(2)O, the Ca(II) ion
      is hepta-coordinated by two N atoms and two O atoms from a tetra-dentate 1,3-bis
      (1H-imidazole-4,5-dicarb-oxy-l-ate) propane dianion and three water O atoms,
      giving a distorted penta-gonal-bipyramidal coordination environment. The Ca-O
      bond lengths are in the range 2.354 (3)-2.453 (2) A, while the Ca-N bond lengths
      are in the range 2.523 (2)-2.548 (2) A. An intra-molecular O-H?O hydrogen bond
      between the carb-oxy and carboxyl-ate groups stabilizes the mol-ecular
      configuration. A three-dimensional network of N-H?O and O-H?O hydrogen bonds help
      to stabilize the crystal packing.

PMID- 22969489
TI  - fac-Bromidotricarbonyl[2-(diisopropylphosphanyl)benzaldehyde
      kappa(2)O,P]rhenium(I).
AB  - The structure of the title complex, [ReBr(C(13)H(19)OP)(CO)(3)], displays a
      facial coordination of the three CO ligands and a kappa(2)O,P coordination mode
      of the 2-diisopropyl-phosphino-benzaldehyde ligands. The Re-C bond distance for
      the CO ligand trans to the P atom is, due to its trans influence, elongated to
      1.943 (3) A, showing that this CO ligand is more weakly bound to the Re centre
      than the other two.

PMID- 22969490
TI  - Tricarbonyl[tris(1-methyl-1H-imidazol-2-yl-kappaN(3))methanol]manganese(I)
      trifluoromethanesulfonate.
AB  - In the title compound, [Mn(C(13)H(16)N(6)O)(CO)(3)](CF(3)O(3)S), the Mn(I) atom
      has a slightly distorted octa-hedral geometry. The three CO ligands have C-Mn-C
      angles in the range 89.44 (10)-92.31 (9) degrees , while the three N atoms of the
      tripodal ligand form significantly smaller N-Mn-N angles of 82.76 (2)-85.51 (6)
      degrees . The three N atoms of the tripodal ligand and the three carbonyl ligands
      coordinate facially. In the crystal, the trifluoro-methane-sulfonate counter
      anion is connected by a medium-strength O-H?O hydrogen bond to the hydroxyl group
      of the manganese complex.

PMID- 22969491
TI  - Poly[[MU-(3-amino-pyridine)-kappa(2)N:N'-MU-chlorido-chlorido(N,N'-dimethyl
      formamide-kappaO)nickel(II)] N,N'-dimethyl-formamide monosolvate].
AB  - The title compound, {[NiCl(2)(C(5)H(6)N(2))(C(3)H(7)NO)].C(3)H(7)NO}(n), is a two
      dimensional polymer in which the Ni(II) atom is coordinated by two N atoms from
      two 3-amino-pyridine ligands, one O atom from a dimethyl-formamide (DMF) group,
      one terminal Cl and two bridging Cl atoms in a distorted octa-hedral geometry.
      The Ni(II) atoms are bridged by the 3-amino-pyridine ligands [Ni?N = 6.7048 (3)
      A] and Cl(-) atoms [Ni?N = 3.5698 (3) A], forming (4,4) two-dimensional nets. The
      DMF solvent mol-ecule and the non-bridged Cl(-) ions participate in N-H?O and N
      H?Cl hydrogen bonds with the amino groups.

PMID- 22969492
TI  - Bis[(1,10-phenanthroline-kappa(2)N,N')bis-(triphenyl-phosphane-kappaP)copper(I)]
      nona-deca-oxidohexa-molybdate(VI).
AB  - The title compound, [Cu(C(12)H(8)N(2))(C(18)H(15)P)(2)](2)[Mo(6)O(19)], was
      obtained by co-crystallization of the mixed-ligand copper complex cation (1,10
      phenanthroline)bis-(triphenyl-phos-phane)copper(I), [Cu(phen)(PPh(3))(2)](+),
      with the Lindquist polyanion [Mo(6)O(19)](2-). The asymmetric unit consists of
      half a Lindquist anion and one [Cu(phen)(PPh(3))(2)](+) cationic complex. In the
      cation, there are intra-molecular pi-pi inter-actions [centroid-centroid
      distances = 3.617 (2) and 3.7272 (18) A]. This inorganic-organic adduct is
      connected by C-H?O hydrogen bonds, forming a two dimensional network lying in the
      ab plane. These networks are connected by C-H?pi inter-actions into a three
      dimensional structure.

PMID- 22969493
TI  - Tetra-MU(3)-hydroxido-tetra-kis-[tricarbonyl-rhenium(I)] pyridine tetra-solvate.
AB  - The title compound, [Re(4)(MU(3)-OH)(4)(CO)(12)].4C(5)H(5)N, crystallizes with
      one tetranuclear rhenium(I) cubane-like molecule and four pyridine mol-ecules in
      the asymmetric unit. The coordination environment of each Re(I) atom is distorted
      octahedral. Four intra-molecular O-H?N and four inter-molecular C-H?O hydrogen
      bond inter-actions are observed. Relatively strong hydrogen bonds are found
      between the hydrogen-bond donor (MU(3)-OH) and acceptor (basic N atom of
      pyridine), with N?O distances between 2.586 (10) and 2.628 (10) A. Inter-cube
      distances of 9.873 (2) and 12.376 (3) A are observed.

PMID- 22969494
TI  - Trichlorido[4-meth-oxy-2,6-bis-(2-pyrimidin-2-yl-kappaN)phenyl
      kappaC(1)]platinum(IV) acetonitrile monosolvate.
AB  - In the title complex, [Pt(C(15)H(11)N(4)O)Cl(3)].CH(3)CN, the Pt(IV) ion adopts a
      distorted octa-hedral coordination geometry defined by a tridentate cyclo
      metalated NCN ligand and three Cl atoms. In the crystal, individual mol-ecules
      are aggregated into a three-dimensional network by C-H?Cl hydrogen-bonding inter
      actions and pi-pi stacking inter-actions between the tridentate ligands, the
      shortest ring centroid-centroid distance being 3.613 A.

PMID- 22969495
TI  - Tetra-butyl-ammonium hydrogen phenyl-arsonate-phenyl-arsonic acid (1/1).
AB  - The structure of the title salt adduct, (C(4)H(9))(4)N(+).C(6)H(5)AsO(3)H(
      ).C(6)H(5)AsO(3)H(2), features chains along the a axis comprising alternating
      hydrogen phenyl-arsonate anions and phenyl-arsonic acid mol-ecules linked by O
      H?O hydrogen bonds.

PMID- 22969496
TI  - (2,3,7,8,12,13,17,18-Octa-ethyl-porphyrinato-kappa(4)N)cobalt(II)-2-nitro
      benzaldehyde (1/2).
AB  - The asymmetric unit of the title compound, [Co(C(36)H(44)N(4))].2C(7)H(5)NO(3),
      is composed of one half of the complex, arranged about an inversion center, and a
      complete 2-nitro-benzaldehyde (NBA) mol-ecule. The structure consists of columns
      that contain inter-leaved mol-ecules of NBA and [Co(II)(OEP)] (OEP is
      2,3,7,8,12,13,17,18-octa-ethyl-porphyrin), which are stacked along the a axis.
      The Co(II) atom is involved in a pi inter-action with the ring of the NBA mol
      ecule with a centroid-metal distance of 3.508 (6) A. There is an intra-molecular
      C-H?O hydrogen bond in the NBA mol-ecule.

PMID- 22969497
TI  - {2,2'-[Cyclo-hexane-1,2-diylbis(nitrilo-methanyl-ylidene)]diphenolato}copper(II).
AB  - The title compound, [Cu(C(20)H(20)N(2)O(2))], crystallizes with two independent
      mol-ecules in the asymmetric unit. In each mol-ecule, the Cu(II) atom occupies
      the tetra-dentate N(2)O(2) cavity of the salen-type Schiff base ligand, adopting
      a distorted square-planar geometry with r.m.s. deviations of the coordin-ating
      atoms of 0.0522 (2) and 0.1128 (4) A. No hydrogen bonds or pi-pi stacking inter
      action are observed.

PMID- 22969498
TI  - Bis[MU-N'-(5-bromo-3-meth-oxy-2-oxido-benzyl-idene)-2-hydroxybenzohydra
      zidato]bis[(N,N-dimethyl-formamide)-copper(II)].
AB  - The title compound, [Cu(2)(C(15)H(11)BrN(2)O(4))(2)(C(3)H(7)NO)(2)], is derived
      from the reaction of N'-(5-bromo-2-hy-droxy-3-meth-oxy-benzyl-idene)-2-hy-droxy
      benzohydrazide and copper nitrate in a dimethyl-formamide solution in the
      presence of sodium hydroxide. The compound can be regarded as a binuclear
      centrosymmetric complex. In the crystal, the Cu(II) atom is fivefold surrounded
      and adopts a distorted square-pyramidal coordination environment. An intra
      molecular O-H?N hydrogen bond stabilizes the mol-ecular conformation.

PMID- 22969499
TI  - Bis[N-benzyl-N-(2-phenyl-eth-yl)dithio-carbamato-kappa(2)S,S']lead(II).
AB  - The mol-ecule of the title compound, [Pb(C(16)H(16)NS(2))(2)], is located on a
      twofold rotation axis, which runs through the Pb(II) atom. The two dithio
      carbamate ligands coordinate the metal in a pyramidal configuration through the S
      atoms. The two phenyl rings of each dithocarbamate ligand are aligned at a
      dihedral angle of 78.4 (1) degrees . The mol-ecular conformation is stabilized by
      intra-molecular C-H?S inter-actions.

PMID- 22969500
TI  - Bis[(cyanido-kappaC)bis(1,10-phenanthroline-kappa(2)N,N')copper(II)] pentakis
      (cyanido-kappaC)nitro-soferrate(II) dimethyl-formamide monosolvate.
AB  - The title compound, [Cu(CN)(C(12)H(8)N(2))(2)](2)[Fe(CN)(5)(NO)].C(3)H(7)NO, is
      formed of discrete [Cu(phen)(2)CN](+) cations (phen is 1,10-phenanthroline),
      nitro-prusside [Fe(CN)(5)(NO)](2-) anions and dimethyl-formamide (DMF) mol-ecules
      of crystallization. The metal atom has a distorted trigonal-bipyra-midal
      coordination environment, defined by four N atoms of two phen mol-ecules and a C
      atom of the cyanide group (in the equatorial position). The [Fe(CN)(5)(NO)](2-)
      anion was found to be disordered about (but not on) a crystallographic twofold
      rotation axis. Geometries were restrained to ideal values. The dimethyl-formamide
      solvent mol-ecule was found to be disordered about a crystallographic inversion
      centre.

PMID- 22969501
TI  - [N-(1-Aza-nidyl-2,2,2-trichloro-ethyl-idene)-2,2,2-trichloro-ethanimidamide]
      copper(II).
AB  - The title compound, [Cu(C(4)H(2)Cl(6)N(3))(2)], was obtained by the reaction of
      CCl(3)CN with ammonia in presence of CuCl. The Cu(II) atom is located about an
      inversion centre. The mol-ecule consists of three planar units (one central
      square CuN(4) and two C(2)N(3) fragments), adopting a staircase-like structure.
      The six-membered metallocycles have a sofa conformation with the Cu atom out of
      the plane of the 1,3,5-triaza-penta-dienyl ligands by 0.246 (5) A. The ipso-C
      atoms of the CCl(3) substituents are slightly out of the 1,3,5-triaza-penta
      dienyl planes by 0.149 (6) and -0.106 (6) A. The CCl(3) groups of each 1,3,5
      triaza-penta-dienyl ligand are practically in the energetic-ally favourable
      mutually eclipsed conformation. In the crystal, the mol-ecules are packed in
      stacks along the a axis. The mol-ecules in the stacks are held together by two
      additional axial Cu?Cl inter-actions of 3.354 (2) A. Taking the axial Cu?Cl inter
      actions into account, the Cu(II) atom exhibits a distorted [4 + 2]-octa-hedral
      coordination environment. The stacks are bound to each other by weak inter
      molecular attractive Cl?Cl [3.505 (2)-3.592 (3) A] inter-actions.

PMID- 22969502
TI  - catena-Poly[[[diaqua-(1,10-phenanthroline-kappa(2)N,N')zinc]-MU-4,4'-bipyridine
      kappa(2)N:N'] dinitrate 4,4'-bipyridine hemisolvate monohydrate].
AB  - In the title compound,
      [Zn(C(10)H(8)N(2))(C(12)H(8)N(2))(H(2)O)(2)](NO(3))(2).0.5C(10)H(8)N(2).H(2)O,
      the Zn(II) atom is coordinated in a distorted octa-hedral geometry by two N atoms
      from two 4,4'-bipyridine (4,4'-bipy) ligands, two N atoms from a chelating 1,10
      phenanthroline ligand and two O atoms from two mutually cis water mol-ecules. The
      4,4'-bipy ligands bridge the Zn(II) atoms into a chain structure along [100]. The
      uncoordinated 4,4'-bipy mol-ecule lies on an inversion center. O-H?O and O-H?N
      hydrogen bonds connect the cationic chains, the nitrate anions, the uncoordinated
      4,4'-bipy mol-ecules and the water mol-ecules into tow-dimensional networks.

PMID- 22969503
TI  - rac-cis-Dicarbonyl-chlorido{1-[2-(diphenyl-phosphanyl-kappaP)benz-yl]-3-(phenyl
      kappaC(1))imidazol-2-yl-idene-kappaC(2)}ruthenium(II) dichloro-methane
      monosolvate.
AB  - In the title compound, [Ru(C(28)H(22)N(2)P)Cl(CO)(2)].CH(2)Cl(2), the Ru(II) atom
      exhibits a distorted octa-hedral coordination geometry. The N-phenyl group of the
      ligand has undergone orthometalation; as a result, the tridentate phosphane
      functionalized N-heterocyclic carbene ligand is coordinating in a meridional
      fashion. This complex is of inter-est with respect to transfer hydrogenation
      catalysis and also provides an example of C-H activation behavior in late
      transition metal complexes. The dichloro-methane solvent mol-ecule is disordered
      over two sets of sites with an occupancy ratio of 0.873 (14):0.127 (14).

PMID- 22969504
TI  - Hexa-kis-{[1-(dimethyl-amino)-propyl-idene]oxidanium} bis-(dodeca-molybdo
      phosphate) N,N-dimethyl-propionamide penta-solvate.
AB  - In the asymmetric unit of the title salt,
      (C(5)H(12)NO)(6)[PMo(12)O(40)](2).5C(5)H(11)NO, there are two independent alpha
      Keggin-type [PMo(12)O(40)](3-) polyoxidoanions, which show characteristic
      features with respect to bond lengths and angles. One of the
      [CH(3)CH(2)C(=OH)N(CH(3))(2)](+) cations is hydrogen bonded to the neighboring
      polyoxidoanion through a C=O-H?O(bridge) hydrogen bond. The organic mol-ecules
      and the remaining organic cations form [(C(5)H(11)NO)(2)H](+) mol-ecule-cation
      pairs, two of which lie about inversion centers, through O-H?O hydrogen bonds.

PMID- 22969505
TI  - Dilithium 1,2,5-thia-diazo-lidine-3,4-dione 1,1-dioxide dihydrate.
AB  - The title compound, poly[MU-aqua-aqua-MU(6)-(1,1-dioxo-1lambda(6),2,5-thia-diazo
      lidine-3,4-diolato)-dilithium], [Li(2)(C(2)N(2)O(4)S)(H(2)O)(2)](n) or
      (H(2)O)(2):Li(2)TDD, forms an infinite three-dimensional structure containing
      five-coordinate (Li/5) and six-coordinate (Li/6) Li(+) cations. Li/5 is
      coordinated by three water mol-ecules, one carbonyl O atom and one sulfuryl O
      atom while Li/6 is coordinated by one water mol-ecule, three carbonyl O atoms,
      and two sulfuryl O atoms. Each water mol-ecule bridges two Li(+) cations, while
      also hydrogen bonding to either one endocyclic N atom and one sulfuryl O atom or
      two endocyclic N atoms. While the endocyclic N atoms in the anion do not
      coordinate the Li(+) cations, the carbonyl and sulfuryl groups each coordinate
      three Li(+) cations, which gives rise to the infinite three-dimensional
      structure.

PMID- 22969506
TI  - cis-Dichloridobis[tris-(4-chloro-phen-yl)phosphane-kappaP]platinum(II)
      acetonitrile monosolvate.
AB  - The title compound, [PtCl(2)(C(18)H(12)Cl(3)P)(2)].C(2)H(3)N, packs as monomeric
      units with a square-planar geometry around the Pt(II) atom. The two tris-(4
      chloro-phen-yl)phosphane ligands are coordinated in a cis orientation, with P-Pt
      P and Cl-Pt-Cl angles of 99.36 (2) and 88.02 (2) degrees , respectively. In the
      crystal, C-H?N inter-actions are observed between the phenyl rings and the
      acetonitrile solvent mol-ecules.

PMID- 22969507
TI  - N-Acetyl-3,5-dibromo-l-tyrosine hemihydrate.
AB  - The title compound, C(11)H(11)Br(2)NO(4).0.5H(2)O, was prepared by an
      electrophilic bromination of N-acetyl-l-tyrosine in acetonitrile at room
      temperature. The two independent mol-ecules do not differ substanti-ally and a
      mol-ecule of water completes the asymmetric unit. The synthesis of the title
      compound does not modify the stereochemical center, as shown by the absolute
      configuration found in this crystal structure. Comparison with the non-bromo
      starting material differs mainly by rotation features. For instance the
      H(methine)-C(chiral center)-C(methyl-ene)-C(ipso) is 173.0 (2) degrees  torsion
      angle in one mol-ecule and 177.3 (2) degrees  in the other, indicating a trans
      arrangement. This is in contrast with approximately 50 degrees  in the starting
      material. A short inter-molecular Br?Br separation is observed [3.2938 (3) A].
      The molecules in the crystal are connected via a network of hydrogen bonds
      through an N-H?O hydrogen bond between the hydroxy group of the phenol of the
      tyrosine and the N-H of the amide of the other molecule and an O-H?O hydrogen
      bond between the hydroxy group of the carboxylic acid and the oxygen of the
      carbonyl of the amide.

PMID- 22969509
TI  - N-(2,6-Diisopropyl-phen-yl)thio-amide.
AB  - In the crystal structure of the title compound, C(13)H(19)NS {systematic name: N
      [2,6-bis-(propan-2-yl)phen-yl]carbothio-amide}, mol-ecules assemble via N-H?S=C
      hydrogen bonds into helical chains along the b axis. The thio-amide moiety, with
      a syn disposition of the N- and C-bound H atoms, is twisted out of the plane of
      the benzene ring to which it is connected, forming a dihedral angle angle of
      77.60 (14) degrees .

PMID- 22969508
TI  - 4-(4-Fluoro-phen-yl)-3-(pyridin-4-yl)-1-(2,4,6-trichloro-phen-yl)-1H-pyrazol-5
      amine.
AB  - In the title compound, C(20)H(12)Cl(3)FN(4), the pyrazole ring forms dihedral
      angles of 47.51 (9), 47.37 (9) and 74.37 (9) degrees  with the directly attached
      4-fluoro-phenyl, pyridine and 2,4,6-trichloro-phenyl rings, respectively. Only
      one of the two amino H atoms is involved in hydrogen bonding. The crystal packing
      is characterized by N-H?N hydrogen bonds, which result in infinite chains
      parallel to the c axis.

PMID- 22969510
TI  - 2-Methyl-sulfan-yl-1H-perimidin-3-ium iodide.
AB  - In the structure of the title salt C(12)H(11)N(2)S(+).I(-), the methyl-sulfanyl
      group of the cation is nearly coplanar with the perimidine rings, as indicated by
      the C-S-C-N torsion angles of 2.9 (5) and -177.2 (3) degrees , respectively. The
      (S)C-N bond lengths in the heterocyclic ring are approximately equal [1.325 (5)
      and 1.326 (6) A] suggesting a degree of delocalization. In the crystal, cations
      and anions are linked via two discrete N-H?I hydrogen bonds, forming chains along
      the b axis.

PMID- 22969511
TI  - 5-Amino-3-eth-oxy-1,8,8-trimethyl-2-aza-bicyclo-[2.2.2]octa-2,5-diene-4,6-dicarbo
      nitrile.
AB  - The title 2-aza-bicyclo-[2.2.2]octa-2,5-diene derivative, C(14)H(18)N(4)O,
      crystallized out with two independent mol-ecules with similar conformations in
      the asymmetric unit. In each mol-ecule, the three six-membered rings adopt boat
      conformations. The mol-ecules exist in the enamine form. In the crystal, mol
      ecules are linked by N-H?O and N-H?N hydrogen bonds into a two-dimensional
      network parallel to the ab plane.

PMID- 22969512
TI  - 9-(Thio-phen-2-yl)-8,9-dihydro-3H-pyrazolo-[4,3-f]quinolin-7(6H)-one ethanol
      monosolvate.
AB  - In the title compound, C(14)H(11)N(3)OS.C(2)H(5)OH, the dihedral angle between
      the pyridine N-C(fused)-C(fused)-C(thio-phene) plane and the plane of the thio
      phene ring is 81.9 (3) degrees , indicating that they are close to perpendicular.
      The dihedral angle between this pyridine plane and the benzene ring is 1.3 (3)
      degrees . The thio-phene ring is disordered over two coplanar orientations with
      an occupancy ratio of 0.692 (7):0.308 (7), while the ethanol solvent mol-ecule is
      also disordered over two sets of site in a 0.66 (4):0.34 (4) ratio. In the
      crystal, chains are formed along the b axis by N-H?O and O-H?N inter-actions with
      adjacent chains being connected through C-H?N and C-H?S inter-actions.

PMID- 22969513
TI  - 3,6-Di-tert-butyl-9-(quinolin-6-yl)-9H-carbazole.
AB  - In the title compound, C(29)H(30)N(2), the dihedral angle between the mean planes
      of the carbazole and the quinoline systems is 52.41 (6) degrees . Mol-ecules are
      linked into dimers by pairs of inter-molecular C-H?N hydrogen bonds and into a
      three-dimensional network by C-H?pi inter-actions.

PMID- 22969514
TI  - Bis-(2-hy-droxy-eth-yl)ammonium 2-bromo-phenolate.
AB  - In the crystal structure of the 1:1 title salt, C(4)H(12)NO(2) (+).C(6)H(4)BrO(
      ), hydrogen-bonding inter-actions originate from the ammonium cation, which
      adopts a syn conformation. A gauche relationship between the C-O and C-N bonds of
      the 2-hy-droxy-ethyl fragments also facilitates O-H?O inter-actions of bis-(2-hy
      droxy-eth-yl)ammonium cation chains to phenolate O atoms. The resulting double
      ion chains along [100] are further linked by N-H?O inter-actions, forming chains
      parallel to [110].

PMID- 22969515
TI  - Dimethyl 3,3'-[(4,5-dicyano-1,2-phenyl-ene)bis-(-oxy)]dibenzoate.
AB  - In the title compound, C(24)H(16)N(2)O(6), the dihedral angles between the
      central 4,5-dicyano-1,2-phenyl-ene unit [maximum deviation from planarity = 0.014
      (4) A] and the pendant benzene rings are 73.62 (5) and 84.08 (6) degrees .

PMID- 22969516
TI  - (1R,4R,5aS,7S,9aS)-7,9a-Dimethyl-6-methyl-ene-3-oxo-1,3,4,5,5a,6,7,8,9,9a-deca
      hydro-naphtho-[1,2-c]furan-1,4-diyl diacetate.
AB  - The title compound, C(19)H(24)O(6), is a sesquiterpene lactone isolated from the
      Kenyan plant Warburgia ugandensis. Ring A adopts a chair conformation, ring B is
      in a C(2) twist conformation and the lactone ring is nearly planar with maximum
      deviation 0.007 (1) A. The reported absolute configuration is based on that of
      the similar compound bromo-parasiticolide A and is supported by analysis of
      Bijvoet differences from light atoms in Mo Kalpha radiation.

PMID- 22969517
TI  - 1-[(Pyridin-3-yl)(pyrrolidin-1-yl)meth-yl]naphthalen-2-ol.
AB  - The title compound, C(20)H(20)N(2)O, was synthesized by a solvent-free one-pot
      three-component domino reaction of naph-tha-len-2-ol, nicotinaldehyde and
      pyrrolidine. The dihedral angle between the naphthalene ring system and the
      pyridine ring is 74.22 (6) degrees . The pyrrolidine ring assumes an envelope
      conformation with the N atom as the flap. An intra-molecular O-H?N hydrogen bond
      stabilizes the mol-ecular conformation.

PMID- 22969518
TI  - 4-Methyl-3-phenyl-2,4-dihydro-pyrazolo-[4,3-c][1,2]benzothia-zine 5,5-dioxide.
AB  - In the title mol-ecule, C(16)H(13)N(3)O(2)S, the heterocyclic thia-zine ring
      adopts a twist chair conformation with the S atom and an adjacent C atom
      displaced by 0.946 (5) and 0.405 (6) A, respectively, on the same side of the
      mean plane formed by the remaining ring atoms. The mean planes of the benzene
      rings make dihedral angles of 16.61 (10) and 15.32 (10) degrees  with the mean
      plane of the pyrazole ring. The mol-ecular structure is consolidated by intra
      molecular C-H?N inter-actions and the crystal packing is stabilized by N-H?O and
      C-H?N hydrogen bonds. The crystal studied was an inversion twin with the refined
      ratio of the twin components being 0.53 (11):0.47 (11).

PMID- 22969519
TI  - 5-Bromo-2-hy-droxy-benzonitrile.
AB  - The title compound, C(7)H(4)BrNO, crystallizes with two mol-ecules in the
      asymmetric unit. The two molecules exhibit nearly linear C-C N nitrile bond
      angles of 179.1 (4) and 177.1 (4) degrees . In the crystal, the mol-ecules are
      linked into a one-dimensional hydrogen-bonded chain by inter-actions between the
      phenol H atom and the nitrile N atom [N?O = 2.805 (4) and 2.810 (4) A].

PMID- 22969520
TI  - 4-[4-(1H-Imidazol-4-yl)phen-yl]-1H-imidazole.
AB  - In the mol-ecule of the title compound, C(12)H(10)N(4), the two imidazole
      substituents are related by inversion symmetry and each forms a dihedral angle of
      25.02 (8) degrees  with the benzene ring. In the crystal, mol-ecules are linked
      through N-H?N hydrogen bonds, forming cyclic units [graph-set R(4) (4)(28)],
      which generate a layered structure extending across (011).

PMID- 22969521
TI  - N-(1,3-Dioxo-2,3-dihydro-1H-isoindol-2-yl)-4,4''-difluoro-5'-hy-droxy-1,1':3',1''
      terphenyl-4'-carboxamide.
AB  - The asymmetric unit of the title compound, C(27)H(16)F(2)N(2)O(4), consists of
      two crystallographically independent mol-ecules (A and B). In mol-ecule B, the
      isoindoline-1,3-dione ring system is disordered over two set of sites with a site
      occupancy ratio of 0.658 (12):0.342 (12). In mol-ecule A, the fluoro-substituted
      benzene rings make dihedral angles of 18.36 (8) and 46.37 (8) degrees  with the
      central benzene ring, whereas the corresponding angles are 40.90 (8) and 52.89
      (9) degrees  in mol-ecule B. The isoindoline ring system in mol-ecule A and the
      major and minor components of the disordered isoindoline ring system in mol-ecule
      B make dihedral angles of 58.50 (4), 54.13 (16) and 70.01 (28)  degrees ,
      respectively, with their attached benzene rings, linked through the amide group.
      An intra-molecular O-H?O hydrogen bond generates an S(6) ring in each mol-ecule.
      In the crystal, mol-ecules are linked by N-H?O, C-H?F and C-H?O hydrogen bonds
      into sheets lying parallel to the bc plane. The crystal studied was a non
      merohedral twin with a refined twin component ratio of 0.9316 (8):0.0684 (8).

PMID- 22969522
TI  - 2,3,5-Triphenyl-2H-tetra-zol-3-ium iodide.
AB  - The asymmetric unit of the title mol-ecular salt, C(19)H(15)N(4) (+).I(-),
      contains four 2,3,5-triphenyl-2H-tetra-zol-3-ium cations and five iodide anions,
      with two of the latter lying on crystallographic inversion centres. In each
      cation, the tetra-zole ring is essentially planar (r.m.s. deviations = 0.004
      0.007 A). The dihedral angles between the tetra-zole ring and its three attached
      benzene rings in the four independent cations are: 12.9 (4), 67.0 (4), 48.1 (4);
      20.8 (4), 51.1 (4), 62.3 (4); 11.4 (4), 52.3 (4), 47.3 (4) and 6.0 (4), 85.7 (4),
      43.5 (4) degrees . A C-H?I hydrogen bond and C-H?pi inter-actions are observed in
      the crystal.

PMID- 22969523
TI  - 5-Hy-droxy-2-{(E)-[(3-nitro-phen-yl)iminio]meth-yl}phenolate.
AB  - The title compound, C(13)H(10)N(2)O(4), crystallized as the zwitterionic
      tautomer. As a result, the phenolate C-O(-) bond [1.296 (2) A] is shorter than a
      normal Csp(2)-O(H) bond, and the azomethine C=N bond [1.314 (2) A] is longer than
      a normal C=N double bond. The mol-ecule is nearly planar, the mean plane of the
      nitro-substituted benzene ring forming dihedral angles of 9.83 (7) and 8.45 (9)
      degrees  with the other benzene ring and with the nitro group, respectively. The
      mol-ecular conformation is stabilized by an intra-molecular N-H?O hydrogen bond.
      In the crystal, strong O-H?O hydrogen bonds link the mol-ecules into double
      stranded chains along the b-axis direction. Within the chains there are pi-pi
      interactions involving the benzene rings of adjacent molecules [centroid-centroid
      distance = 3.669 (1) A]. The chains are linked via C-H?O hydrogen bonds, forming
      R(2) (1)(6), R(2) (1)(7) and R(2) (2)(10) ring motifs.

PMID- 22969524
TI  - 4-Cyano-anilinium iodide.
AB  - In the title compound, C(7)H(7)N(2) (+).I(-), the cation is located on a site of
      4mm symmetry and is thus disordered about the fourfold axis so that there are two
      perpendicular orientations of the six-membered ring and four rotational
      orientations of the {-NH(3) (+)} group. In the crystal, there are two layers
      perpendicular to the c axis, each containing iodide ions and the {-NH(3) (+)}
      portions of the cations, with the remainder of the cations extending outwards
      from these layers.

PMID- 22969525
TI  - (10E,12E,14E)-9,16-Dioxoocta-deca-10,12,14-trienoic acid.
AB  - The title octa-deca-trienoic acid derivative, C(18)H(26)O(4), was isolated from
      Silene maritima With. (Caryophyllaceae), the first time this natural compound has
      been found in the Caryophyllales order. This fatty acid has an 18-carbon backbone
      with three double bonds on trans (E) conformation and two carbonyl. In the
      crystal, molecules are linked via pairs of O-H?O hydrogen bonds, forming
      inversion dimers.

PMID- 22969526
TI  - 1-[4-(4-Fluoro-phen-yl)-6-methyl-2-sulfanyl-idene-1,2,3,4-tetra-hydro-pyrimidin-5
      yl]ethanone.
AB  - In the title mol-ecule, C(13)H(13)FN(2)OS, the heterocyclic ring adopts a
      slightly distorted flattened boat conformation, and the plane through the four
      coplanar atoms makes a dihedral angle of 87.45 (14) degrees  with the benzene
      ring. The thione, acetyl and methyl groups lie on the opposite side of the
      heterocyclic mean plane to the fluorophenyl group, which has an axial
      orientation. N-H?O, N-H?S, C-H?F and C-H?O inter-molecular hydrogen bonds and a
      weak C-H?pi inter-action involving the benzene ring are found in the crystal
      structure.

PMID- 22969527
TI  - N-[(4-Chloro-phen-yl)sulfon-yl]acetamide.
AB  - The asymmetric unit of the title compound, C(8)H(8)ClNO(3)S, consists of two
      crystallographically independent mol-ecules (A and B). The dihedral angles
      between the benzene ring and amide C-C(=O)-NH- plane are 87.6 (3) (mol-ecule A)
      and 86.0 (3) degrees  (mol-ecule B). In the crystal, the independent mol-ecules
      are alternately linked by N-H?O hydrogen bonds into an infinite chain along the b
      axis. Short inter-molecular Cl?Cl contacts [3.2882 (5) and 3.2812 (5) A] are also
      observed.

PMID- 22969528
TI  - N-(3-Methyl-phen-yl)-2-nitro-benzene-sulfonamide.
AB  - In the title compound, C(13)H(12)N(2)O(4)S, the dihedral angle between the
      benzene rings is 73.64 (7) degrees . The amide H atom exhibits bifurcated
      hydrogen bonding: an intra-molecular N-H?O hydrogen bond generates an S(7) motif
      while in the crystal, N-H?O(S) hydrogen bonds link the mol-ecules into zigzag
      C(4) chains running along the b axis.

PMID- 22969529
TI  - An ortho-rhom-bic polymorph of 2-(1,3-benzothia-zol-2-yl)-6-eth-oxy-phenol.
AB  - In the title mol-ecule, C(15)H(13)NO(2)S, an intra-molecular O-H?N hydrogen bond
      forms an S(6) ring motif. The benzothia-zole ring system and the benzene ring
      form a dihedral angle of 8.9 (3) A. In the crystal, mol-ecules are linked by weak
      C-H?O hydrogen bonds, forming chains along the b axis. In addition, pi-pi inter
      actions [centroid-centroid distances = 3.772 (4) and 3.879 (4) A] are observed.

PMID- 22969530
TI  - 2-[(E)-(Naphthalen-2-yl)imino-meth-yl]phenol.
AB  - In the title compound, C(17)H(13)NO, the azomethine double bond adopts an E
      conformation. The naphthyl ring system and the benzene ring form a dihedral angle
      of 8.09 (10) degrees . The near-planar conformation of the molecule is
      consolidated by an intra-molecular O-H?N hydrogen bond, which forms an S(6) ring.
      In the crystal, mol-ecules are arranged in a zigzag fashion parallel to the c
      axis.

PMID- 22969531
TI  - 2-Methyl-3-nitro-N-{(E)-[5-(4-nitro-phen-yl)furan-2-yl]methyl-idene}aniline.
AB  - In the title Schiff-base type compound, C(18)H(13)N(3)O(5), the central furan
      ring makes dihedral angles of 12.80 (7) and 51.43 (4) degrees  with the terminal
      benzene rings. The dihedral angle between the benzene rings is 45.43 (3) degrees
      . In the crystal, C-H?O hydrogen bonds link the mol-ecules into layers parallel
      to (010). In addition, there are pi-pi stacking inter-actions within the layer
      [centroid-centroid distance = 3.584 (1) A] and between the layers [centroid
      centroid distance 3.751 (1) A].

PMID- 22969532
TI  - [1-Meth-oxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2-yl)methanone.
AB  - Methyl-ation of [1-hy-droxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2
      yl)methanone was performed via metalation with potassium tert-butano-late in
      toluene and a subsequent metathesis reaction with methyl iodide yielded the
      yellow title compound, C(20)H(15)N(3)O(2). The substituents at the indolizine
      unit are twisted [the indolizine ring system makes dihedral angles of 34.67 (7)
      and 77.49 (5) degrees , respectively, with the pyridyl and pyridinoyl rings] with
      single bonds between the central unit and the attached pyridine ring [1.459 (3)
      A] and the pyridinoyl group [1.483 (3) A]. There are no classical hydrogen bonds
      in the crystal structure.

PMID- 22969533
TI  - (E)-{[But-2-ene-1,4-diylbis(-oxy)]bis-(4,1-phenyl-ene)}bis-(phenyl-methanone).
AB  - The title mol-ecule, C(30)H(24)O(4), lies about an inversion center located at
      the mid-point of the central C=C bond. The diphenyl-methanone unit adopts an all
      trans conformation. The dihedral angle between the adjacent rings is 53.57 (4)
      degrees .

PMID- 22969534
TI  - 1-[3-(4-Fluoro-phen-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone.
AB  - In the title compound, C(17)H(15)FN(2)O, the pyrazoline ring adopts a flattened
      envelope conformation. The dihedral angle between the fluoro-substituted benzene
      ring and the phenyl ring is 69.20 (5) degrees . In the crystal, a pair of C-H?O
      hydrogen bonds link neighbouring mol-ecules, forming an inversion dimer. The
      crystal structure is further consolidated by C-H?pi inter-actions and by a pi-pi
      inter-action with a centroid-centroid distance of 3.7379 (6) A.

PMID- 22969535
TI  - 4-Bromo-2-[(E)-(2-{2-[(2-{[(E)-5-bromo-2-hy-droxy-benzyl-idene]amino}-phen
      yl)sulfan-yl]ethyl-sulfan-yl}phen-yl)imino-meth-yl]phenol.
AB  - The asymmetric unit of the title compound, C(28)H(22)Br(2)N(2)O(2)S(2), comprises
      half of a Schiff base ligand, the whole mol-ecule being generated by a
      crystallographic inversion center located at the mid-point of the C-C bond of the
      central methyl-ene segment. Intra-molecular O-H?N and O-H?S hydrogen bonds make
      S(6) and S(5) ring motifs, respectively. In the crystal, there are no significant
      inter-molecular inter-actions.

PMID- 22969536
TI  - 2-(6-Meth-oxy-naphthalen-2-yl)-1-(morpholin-4-yl)propan-1-one.
AB  - In the title compound, C(18)H(21)NO(3), the naphthalene group and the basal plane
      of the morpholine ring (r.m.s. deviations = 0.0177 and 0.0069 A, respectively)
      are oriented at a dihedral angle of 44.0 (2) degrees . In the crystal, mol-ecules
      are linked by C-H?pi inter-actions.

PMID- 22969537
TI  - 2-(4-Isobutyl-phen-yl)-1-(morpholin-4-yl)propan-1-one.
AB  - In the title compound, C(17)H(25)NO(2), the morpholine ring adopts a chair
      conformation. The benzene ring makes a dihedral angle of 39.81 (13) degrees  with
      the basal plane of the morpholine group.

PMID- 22969538
TI  - 2,2'-[(4-Eth-oxy-phen-yl)methyl-ene]bis-(3-hy-droxy-5,5-dimethyl-cyclo-hex-2-en-1
      one).
AB  - In the title compound, C(25)H(32)O(5), the two cyclo-hexenone rings have envelope
      conformations with the C atom bearing two methyl groups as the flap atom in each
      ring. Relatively strong intra-molecular O-H?O hydrogen bonds are observed.

PMID- 22969539
TI  - 2-propoxybenzamide.
AB  - In the title mol-ecule, C(10)H(13)NO(2), the amide -NH(2) group is oriented
      toward the prop-oxy substituent and an intra-molecular N-H?O hydrogen bond is
      formed between the N-H group and the prop-oxy O atom. The benzene ring forms
      dihedral angles of 12.41 (2) and 3.26 (2) degrees  with the amide and prop-oxy
      group mean planes, respectively. In the crystal, N-H?O hydrogen bonds order pairs
      of mol-ecules with their mol-ecular planes parallel, but at an offset of 0.73 (2)
      A to each other. These pairs are ordered into two types of symmetry-related
      columns extended along the a axis with the mean plane of a pair in one column
      approximately parallel to (-122) and in the other to (-1-22). The two planes form
      dihedral angle of 84.40 (1) degrees . Overall, in a three-dimensional network,
      the hydrogen-bonded pairs of mol-ecules are either located in (-1-22) or (-122)
      layers. In one layer, each pair is involved in four C-H?O contacts, twice as a
      donor and twice as an acceptor. Additionally, there is a short C-H?C contact
      between a benzene C-H group and the amide pi-system.

PMID- 22969540
TI  - 1-[4-(4-Isopropyl-phen-yl)-6-methyl-2-sulfanyl-idene-1,2,3,4-tetra-hydro
      pyrimidin-5-yl]ethanone.
AB  - In the title mol-ecule, C(16)H(20)N(2)OS, the heterocyclic ring adopts a slightly
      distorted flattened boat conformation, and the plane through the four coplanar
      atoms makes a dihedral angle of 86.98 (6) degrees  with the benzene ring. The
      thione, acetyl and methyl groups lie on the opposite side of the heterocyclic
      mean plane to the isopropylphenyl group which has an axial orientation. A weak
      intra-molecular C-H?O hydrogen bond is observed. In the crystal, molecules are
      linked via N-H?O, N-H?S and C-H?S hydrogen bonds.

PMID- 22969541
TI  - 4,6-Dibromo-isophthalic acid monohydrate.
AB  - In the crystal structure of the title hydrate, C(8)H(4)Br(2)O(4).H(2)O, O-H?O
      hydrogen bonds link the mol-ecules into a two-dimensional network parallel to (10
      2). The acid groups of the main mol-ecule and the water mol-ecule are all
      involved in the supra-molecular structure. The dihedral angles between the
      benzene ring and the acid groups are 37.8 (4) and 36.4 (5) degrees , while the
      dihedral angle between the acid groups is 10.9 (4) degrees .

PMID- 22969542
TI  - 2-{[2-(1-Methyl-2,2-dioxo-3,4-dihydro-1H-2lambda(6),1-benzothia-zin-4-yl
      idene)hydrazin-1-yl-idene]meth-yl}phenol.
AB  - In the title compound, C(16)H(15)N(3)O(3)S, the dihedral angle between the
      aromatic rings is 8.18 (11) degrees  and the C=N-N=C torsion angle is 178.59 (14)
      degrees . The conformation of the thia-zine ring is an envelope, with the S atom
      displaced by 0.8157 (18) A from the mean plane of the other five atoms (r.m.s.
      deviation = 0.045 A). An intra-molecular O-H?N hydrogen bond closes an S(6) ring.
      In the crystal, weak C-H?O inter-actions link the mol-ecules, with all three O
      atoms acting as acceptors.

PMID- 22969543
TI  - (Z)-2-[Meth-oxy(phen-yl)methyl-idene]-3,4,5-trimethyl-2,3-dihydro-1,3-thia-zole.
AB  - In the title compound, C(14)H(17)NOS, the plane defined by the bridging methyl
      ene C atom and its three substituents makes dihedral angles of 14.37 (8) degrees 
      with the heterocycle and 26.17 (8) degrees  with the phenyl ring, while the
      dihedral angle between the heterocycle and the phenyl ring is 36.29 (7) degrees .
      In the crystal, mol-ecules are linked by C-H?pi contacts.

PMID- 22969545
TI  - 4-[(E)-(4-Eth-oxy-phen-yl)imino-meth-yl]phenol.
AB  - In the title compound, C(15)H(15)NO(2), the dihedral angle between the benzene
      rings is 52.04 (5) degrees  and the mol-ecule has an E conformation about the
      central C=N bond. In the crystal, mol-ecules are connected by O-H?N hydrogen
      bonds, forming zigzag chains along the b axis. The crystal packing also features
      weak C-H?O inter-actions.

PMID- 22969544
TI  - 3-Phenyl-coumarin.
AB  - In the title compound, C(15)H(10)O(2), a 3-phenyl derivative of the coumarin
      (also known as 2H-chromen-2-one or 2H-1-benzopyran-2-one) scaffold, the C(p)-C(p)
      C(c)-C(c) torsion angle between the coumarin (c) ring system and the phenyl (p)
      ring is -47.6 (2) degrees .

PMID- 22969546
TI  - 5a-Butyl-1,3,8,10-tetra-chloro-7,13-bis-(4-nitro-benzo-yl)-5a,6a,12a,12b-tetra
      hydro-7H,13H-thieno[2,3-b:4,5-b']bis-(1,4-benzoxazine).
AB  - The title compound, C(34)H(24)Cl(4)N(4)O(8)S, is a linear penta-cyclic system
      formed of two substituted benzoxazinyl groups fused to 2-n-butyl-tetra-hydro-thio
      phene. The oxazine ring, which is fused to the n-butyl-substituted side of the
      thio-phene ring, is in a boat conformation. The other fused oxazine ring and the
      tetra-hydro-thiene ring are each in an envelope conformation. The bridgehead C
      atom alpha to both the S and N atoms forms the flap of each envelope. This
      results in a twist of the penta-cyclic system such that the dihedral angle
      between the terminal dichloro-benzene rings is 82.92 (8) degrees . In the
      crystal, inversion-related mol-ecules form a weakly hydrogen-bonded dimer, with
      two C-H?O inter-actions between an H atom on the oxazine ring and an amide O
      atom. Additionally, C-H?O inter-actions occur between an H atom on a screw
      related nitro-benzene ring and an O atom on the nitro-benzene ring of one mol
      ecule. One of the Cl atoms and the butyl group are disordered over two sets of
      sites with occupancy ratios of 0.94 (2):0.06 (2) and 0.624 (4):0.376 (4),
      respectively.

PMID- 22969548
TI  - N,N-Dimethyl-N',N''-bis-(2-methyl-phenyl)phospho-ric triamide mono-hydrate.
AB  - In the title compound, C(16)H(22)N(3)OP.H(2)O, the P atom adopts a distorted
      tetra-hedral environment with the bond angles around the P atom in the range
      99.98 (7)-116.20 (7) degrees . The P-N bond length in the [(CH(3))(2)N]P(O)
      fragment [1.6392 (14) A] is slightly shorter than two other P-N bonds [1.6439
      (15) and 1.6530 (14) A]. In the (CH(3))(2)NP(O) fragment, one of the methyl
      groups is syn to the P=O bond, whereas the other one is anti to the P=O bond [C-N
      P=O torsion angles = 4.80 (17) and -174.57 (15) degrees ]. In the crystal, the
      water mol-ecules form hydrogen bonds to the O atoms of the P=O bond of two
      different mol-ecules and act as acceptors for the two amino H atoms of the same
      mol-ecule. As a result, chains parallel to [010] are formed.

PMID- 22969547
TI  - N-(2-Methyl-phen-yl)-2-nitro-benzene-sulfonamide.
AB  - In the title compound, C(13)H(12)N(2)O(4)S, the dihedral angle between the
      benzene rings is 53.44 (14) degrees . The amide H atom exhibits bifurcated
      hydrogen bonding: an intra-molecular N-H?O hydrogen bond generates an S(7) motif
      while in the crystal, N-H?O(S) hydrogen bonds link the mol-ecules into zigzag
      C(4) chains along the c axis.

PMID- 22969549
TI  - 2-Nitro-N-phenyl-benzene-sulfonamide.
AB  - In the title compound, C(12)H(10)N(2)O(4)S, the conformation of the N-H bond in
      the -SO(2)-NH- fragment is syn to the ortho-nitro group in the sulfonyl-benzene
      ring. The mol-ecule is twisted at the S-N bond, the C-N-S-C torsion angle being 
      72.83 (15) degrees . The dihedral angle between the benzene rings is 59.55 (7)
      degrees . The amide H atom and the nitro group O atom form an intra-molecular
      hydrogen bond, generating an S(7) motif. In the crystal, C-H?O hydrogen-bond
      inter-actions link the mol-ecules into S(2) (2)(10) networks.

PMID- 22969550
TI  - 4-Nitro-1-[(trimethyl-sil-yl)ethyn-yl]benzene: low-temperature polymorph at 100
      K.
AB  - The title compound, C(11)H(13)NO(2)Si, is a low-temperature form of the
      previously reported room-temperature structure [Garcia et al. (1998 ?). Acta
      Cryst. C54, 489-491]. At 298 K, the material crystallizes in the space group Pnma
      and occupies a crystallographic mirror plane, but at 100 K the space group
      changes to P2(1)2(1)2(1), the volume decreases by 5% and the mol-ecule distorts.
      The greatest mol-ecular distortions from C(s) symmetry are rotations of the
      trimethyl-silyl and nitro groups by 10.56 (8) and 11.47 (9) degrees ,
      respectively, to the benzene mean plane. At low temperature, the crystal also
      becomes an inversion twin, the refined ratio of the twin components being 0.35
      (15):0.65 (15).

PMID- 22969551
TI  - (3,6-Dimeth-oxy-naphthalen-2-yl)(naphthalen-2-yl)methanone.
AB  - In the title compound, C(23)H(18)O(3), the dihedral angle between the two
      naphthalene ring systems is 78.02 (3) degrees . The bridging carbonyl C-C(=O)-C
      plane makes a dihedral angle of 70.56 (5) degrees  with the naphthalene ring
      system in the 2,7-dimeth-oxy-naphthalene moiety and a dihedral angle of 11.53 (5)
      degrees  with the naphthalene ring system in the naphthoyl group. In the crystal,
      adjacent mol-ecules are linked via C-H?pi inter-actions, forming chains along
      [010].

PMID- 22969552
TI  - 5-(5-Bromo-2-meth-oxy-phen-yl)-2-fluoro-pyridine.
AB  - In the title compound, C(12)H(9)BrFNO, the dihedral angle between the aromatic
      rings is 51.39 (5) degrees ; the C atom of the meth-oxy group is close to being
      coplanar with its attached ring (r.m.s. deviation = 0.0172 A] and is oriented
      away from the pyridine ring. In the crystal, mol-ecules inter-act by van der
      Waals forces.

PMID- 22969553
TI  - 1-[5-(4-Bromo-phen-yl)-3-(4-fluoro-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]butan-1
      one.
AB  - In the title compound, C(19)H(18)BrFN(2)O, the benzene rings form dihedral angles
      of 5.38 (7) and 85.48 (7) degrees  with the mean plane of the 4,5-dihydro-1H
      pyrazole ring (r.m.s. deviation = 0.0849 A), which approximates to an envelope
      conformation with the -CH(2)- group as the flap. The dihedral angle between the
      benzene rings is 82.86 (7) degrees . In the crystal, C-H?F and C-H?O hydrogen
      bonds link the mol-ecules to form inversion dimers and together these generate
      chains along [011]. The crystal packing also features C-H?pi inter-actions.

PMID- 22969554
TI  - N-(2-Bromo-phen-yl)-2-(naphthalen-1-yl)acetamide.
AB  - In the title compound, C(18)H(14)BrNO, the naphthalene ring system [maximum
      deviation = 0.015 (3) A] forms a dihedral angle of 67.70 (10) degrees  with the
      benzene ring. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds into
      C(4) chains propagating in [100]. A C-H?O inter-action reinforces the chain
      connectivity, generating an R(2) (1)(6) loop.

PMID- 22969555
TI  - (2E)-3-(2-Fluoro-phen-yl)-1-(4-fluoro-phen-yl)prop-2-en-1-one.
AB  - In the title compouund, C(15)H(10)F(2)O, the mol-ecule exists in an E
      conformation with respect to the C=C bond [1.3382 (16) A]. The dihedral angle
      between the fluoro-substituted benzene rings is 6.80 (6) degrees  and the whole
      mol-ecule is roughly planar (r.m.s. deviation for the non-H atoms = 0.069 A). In
      the crystal, mol-ecules are linked by C-H?F and C-H?O inter-actions into sheets
      lying parallel to the bc plane.

PMID- 22969556
TI  - 2,2-Diphenyl-N-(2,4,5-trichloro-phen-yl)acetamide.
AB  - The asymmetric unit of the title compound, C(20)H(14)Cl(3)NO, consists of two
      independent mol-ecules. In one mol-ecule, the chlorinated benzene ring forms
      dihedral angles of 12.00 (9) and 77.04 (9) degrees  with the phenyl rings. The
      dihedral angle between the phenyl rings is 80.37 (10) degrees . The corresponding
      dihedral angles for the other mol-ecule are 26.34 (10), 62.98 (10) and 88.47 (11)
      degrees , respectively. One of the mol-ecules features an intra-molecular C-H?O
      hydrogen bond, which forms an S(6) ring motif. In the crystal, mol-ecules are
      linked by N-H?O hydrogen bonds into [100] chains. The chains are further linked
      by C-H?O and C-H?Cl hydrogen bonds into a three-dimensional network.

PMID- 22969557
TI  - 4-Hy-droxy-benzamide 1,4-dioxane hemisolvate.
AB  - The asymmetric unit of the title compound, C(7)H(7)NO(2).0.5C(4)H(8)O(2), is
      composed of one 4-hy-droxy-benzamide mol-ecule and half of a 1,4-dioxane mol
      ecule. The complete dioxin molecule is generated by crystallographic inversion
      symmetry. The crystal has an extensive system of hydrogen bonds, in which the
      three donor H atoms are fully utilized: these result in amide-amide homodimers,
      and N-H?O(dioxane) and O-H?O(amide) links.

PMID- 22969558
TI  - tert-But-yl(2-hy-droxy-eth-yl)aza-nium 4-[(1,3-thia-zol-2-yl-aza-nid-yl)sulfon
      yl]aniline.
AB  - Two pairs of independent cations and anions comprise the asymmetric unit of the
      title salt, C(6)H(16)NO(+).C(9)H(8)N(3)O(2)S(2) (-). The cations are virtually
      superimposable and each exhibits a gauche disposition of the hy-droxy O and
      ammonium N atoms [the O-C-C-N torsion angles are 55.5 (3) and 57.5 (3) degrees ].
      Significant differences are seen in the mol-ecular structures of the anions as
      seen in the S-N-C-S [1.1 (3) and 32.9 (3) degrees ] and C-S-N-C [-69.7 (2) and
      91.4 (2) degrees ] torsion angles. Despite the variations in conformation, intra
      molecular hypervalent S?O inter-actions persist in each anion [3.078 (2) and
      2.8730 (19) A]. In the crystal, supra-molecular double layers are formed in the
      bc plane, being sustained by O-H?N, N-H?O and N-H?N hydrogen bonding. These are
      connected along the a axis via C-H?O inter-actions.

PMID- 22969559
TI  - 4-[5-(4-Formyl-phen-oxy)pent-oxy]benzaldehyde.
AB  - In the title compound, C(20)H(19)O(4), the benzene rings, linked via five methyl
      ene C atoms, form a dihedral angle of 77.28 (6) degrees . In the crystal, mol
      ecules are linked via pairs of weak C-H?O inter-actions [graph set R(2) (2)(6)]
      into dimers that are further connected by additional weak C-H?O interactions
      [graph sets R(2) (2)(14), R(2) (2)(26) and R(2) (2)(6)].

PMID- 22969560
TI  - 2-Benzene-sulfonamido-3-methyl-butyric acid.
AB  - In the crystal structure of the title compound, C(11)H(15)NO(4)S, two independent
      mol-ecules are present per asymmetric unit; they are dimerized through O-H?O
      hydrogen bonds between their carb-oxy groups to generate R(2) (2)(8) loops. An
      intra-molecular N-H?O link in one of the mol-ecules closes an S(5) ring. The
      dimers are linked by N-H?O and C-H?O hydrogen bonds to form a three-dimensional
      network. The C atoms of the isopropyl group of one of the mol-ecules are
      disordered over two orientations in a 3:1 ratio.

PMID- 22969561
TI  - 4-Chloro-1H-pyrrolo-[2,3-d]pyrimidine.
AB  - The title compound, C(6)H(4)ClN(3), is essentially planar with the pyrrole and
      pyrimidine rings inclined to one another by 0.79 (15) degrees . In the crystal,
      mol-ecules are connected via pairs of N-H?N hydrogen bonds, forming inversion
      dimers. These dimers are linked via C-H?N inter-actions, forming a two
      dimensional network parallel to (10-1).

PMID- 22969562
TI  - 4-Isopropyl-5,5-dimethyl-2-sulfanyl-1,3,2-dioxaphosphinane 2-sulfide.
AB  - The title compound, C(8)H(17)O(2)PS(2), displays a distorted tetra-hedral
      geometry around the P atom. The P atom is part of a six-membered ring with an
      isopropyl group in the equatorial position. The mol-ecules are linked by S-H?S
      hydrogen bonds in the crystal packing.

PMID- 22969563
TI  - Monoclinic polymorph of 2,5-dide-oxy-2,5-epithio-1,3:4,6-bis-O-[(R)-phenyl-methyl
      ene]-l-iditol.
AB  - The title compound C(20)H(20)O(4)S, is polymorphic. In the tetra-gonal form, the
      mol-ecule lies on a crystallographic twofold axis, while the monoclinic form has
      only approximate C(2) mol-ecular symmetry. The greatest excursion from C(2)
      symmetry is in the orientation of the two phenyl rings; at 100 K, one of the
      rings is rotated -37.2 (3) degrees  and the other by 46.9 (3) degrees  from their
      symmetric (tetra-gonal) positions. There are only minor differences in the three
      ring nucleus; the best mol-ecular fit of the tetra-gonal and monoclinic forms,
      both at 100 K and excluding phenyl rings and H atoms, shows an r.m.s. deviation
      of 0.066 A. Both forms have the same absolute configuration.

PMID- 22969564
TI  - 4-tert-Butyl-N-[(2,6-dimethyl-phen-yl)carbamothio-yl]benzamide.
AB  - The asymmetric unit of the title compound, C(20)H(24)N(2)OS, consists of two
      crystallographically independent mol-ecules. In each mol-ecule, an intra
      molecular N-H?O hydrogen bond forms an S(6) ring motif. The dihedral angles
      between the terminal benzene rings in the two mol-ecules are 75.52 (7) and 42.80
      (7) degrees . In the crystal, inter-molecular N-H?S inter-actions link the mol
      ecules into a chain along the c axis.

PMID- 22969565
TI  - Methyl (E)-3,5-dimeth-oxy-2-{[2-(4-meth-oxy-benzo-yl)hydrazin-1-yl-idene]meth
      yl}benzoate.
AB  - In the title compound, C(19)H(20)N(2)O(6), the azomethine [C=N = 1.269 (2) A]
      double bond adopts an E conformation and the dihedral angle between the planes of
      the benzene rings is 17.41 (11) degrees . In the crystal, inversion dimers linked
      by pairs of N-H?O hydrogen bonds generate R(2) (2)(16) loops. The dimers are
      connected by C-H?O and C-H?N hydrogen bonds, forming sheets lying parallel to
      (100).

PMID- 22969566
TI  - 2,5-Dichloro-3,6-diisopropyl-cyclo-hexa-2,5-diene-1,4-dione.
AB  - The mol-ecule of the title compound, C(12)H(14)Cl(2)O(2), lies about an inversion
      center. The six-membered ring is almost planar, with the largest deviation from
      the least-squares plane being 0.014 (4) A. The mol-ecular conformation is
      stabilized by a weak intra-molecular C-H?O hydrogen bond. In the crystal, mol
      ecules are packed into stacks along the c-axis direction, with an inter-centroid
      separation of 4.811 (2) A. Neighboring mol-ecules within the stack are related by
      the c-glide plane.

PMID- 22969567
TI  - (Z)-3-Meth-oxy-N-[(5-nitro-thio-phen-2-yl)methyl-idene]aniline.
AB  - In the title compound, C(12)H(10)N(2)O(3)S, the dihedral angle between the
      benzene and thio-phene rings is 43.17 (4) degrees . The crystal structure is
      devoid of any hydrogen-bonding inter-actions. However, pi-pi inter-actions
      between the benzene and thio-phene rings [distance between ring centroids =
      3.6850 (11) A] stack the mol-ecules along the a axis. The absolute structure
      could not be determined as the crystal studied was a racemic twin with a BASF
      parameter of 0.31 (6).

PMID- 22969568
TI  - 2-[(8-Meth-oxy-carbonyl-4b,8-dimethyl-4b,5,6,7,8,8a,9,10-octa-hydro-phenan-thren
      3-yl)amino]-3,5-dinitro-benzoic acid ethyl acetate monosolvate.
AB  - The title compound, C(25)H(27)N(3)O(8).C(4)H(8)O(2), has a diterpene skeleton in
      which the fused cyclo-hexane rings exhibit chair and half-chair conformations. An
      intra-molecular C-H?O hydrogen bond occurs. In the crystal, N-H?O, O-H?O and C
      H?O hydrogen bonds are observed.

PMID- 22969569
TI  - 2-Cyclo-pentyl-idenehydrazine-carboxamide.
AB  - The asymmetric unit of the title compound, C(6)H(11)N(3)O, consists of two
      independent mol-ecules in which the cyclo-pentane rings adopt envelope
      conformations with CH(2) grouping as the flap and the semicarbazone groups are
      essentially planar, with maximums deviation of 0.0311 (12) and 0.0285 (12) A. In
      the crystal, N-H?O, N-H?N and C-H?O hydrogen bonds link the mol-ecules to form
      sheets lying parallel to the ab plane.

PMID- 22969570
TI  - N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-[4-(methyl-sulfan
      yl)phen-yl]acetamide.
AB  - In the title compound, C(20)H(21)N(3)O(2)S, the 2,3-dihydro-1H-pyrazole ring is
      nearly planar (r.m.s. deviation = 0.023 A) and forms dihedral angles of 16.96 (6)
      and 38.93 (6) degrees  with the benzene and phenyl rings, respectively. The
      dihedral angle between the benzene and phenyl rings is 55.54 (6) degrees . The
      mol-ecular conformation is consolidated by an intra-molecular C-H?O hydrogen
      bond, which forms an S(6) ring. In the crystal, inversion dimers linked by pairs
      of N-H?O(p) (p = pyrazole) hydrogen bonds generate R(2) (2)(10) loops. The dimers
      are linked by C-H?O hydrogen bonds into sheets lying parallel to (100).

PMID- 22969571
TI  - 2-(4-Bromo-phen-yl)-N-(2,6-dimethyl-phen-yl)acetamide.
AB  - In the title compound, C(16)H(16)BrNO, the dihedral angle between the benzene
      rings is 69.8 (2) degrees . In the crystal, N-H?O hydrogen bonds link the mol
      ecules into C(4) chains propagating in [100]. Adjacent mol-ecules in the chains
      are also linked by C-H?O inter-actions which, along with the N-H?O hydrogen
      bonds, generate R(2) (1)(6) loops.

PMID- 22969572
TI  - 2-(4-Chloro-phen-yl)-N-(1,3-thia-zol-2-yl)acetamide.
AB  - In the title compound, C(11)H(9)ClN(2)OS, the thia-zole ring is nearly planar
      (r.m.s. deviation = 0.003 A) and forms a dihedral angle of 64.18 (7) degrees 
      with the bezene ring. In the crystal, inversion dimers linked by pairs of N
      H?N(t) (t = thia-zole) hydrogen bonds generate R(2) (2)(8) loops.

PMID- 22969573
TI  - 5-(4-Bromo-phen-yl)-3-(4-fluoro-phen-yl)-1-phenyl-4,5-dihydro-1H-pyrazole.
AB  - In the title compound, C(21)H(16)BrFN(2), the fluoro-substituted benzene ring is
      disordered over two orientations about the C-F bond and the C-C bond between the
      benzene and pyrazole groups with a site-occupancy ratio of 0.516 (8):0.484 (8).
      The central pyrazole ring [maximum deviation = 0.035 (3) A] makes dihedral angles
      of 22.4 (2), 11.0 (2), 77.19 (16) and 7.44 (17) degrees  with the two disorder
      components of the benzene ring, the bromo-substituted benzene ring and the phenyl
      ring, respectively. In the crystal, mol-ecules are linked into a layer parallel
      to the bc plane through C-H?pi inter-actions.

PMID- 22969574
TI  - 2,3-Dibromo-3-(4-chloro-phen-yl)-1-(4-nitro-thio-phen-2-yl)propan-1-one.
AB  - The title compound, C(13)H(8)Br(2)ClNO(3)S, exhibits whole-mol-ecule disorder
      over two orientations in a 0.805 (6):0.195 (6) ratio. The dihedral angles between
      the thio-phene ring [maximum deviations = 0.017 (4) and 0.033 (9) A for the major
      and minor components, respectively] and the chloro-substituted phenyl ring are
      32.1 (5) (major component) and 26.3 (18) degrees  (minor component). In the
      crystal, C-H?Cl and C-H?O hydrogen bonds link the mol-ecules into sheets lying
      parallel to the bc plane. Aromatic pi-pi stacking inter-actions [centroid
      centroid distance = 3.550 (7) A] are also observed.

PMID- 22969575
TI  - 1-(6-Chloro-1,3-benzothia-zol-2-yl)-2-[1-(4-meth-oxy-phen-yl)ethyl
      idene]hydrazine.
AB  - The asymmetric unit of the title compound, C(16)H(14)ClN(3)OS, contains two
      independent mol-ecules (A and B) linked into dimers via N-H?N hydrogen bonds. The
      1,3-benzothia-zol-2-yl ring system and the benzene ring form dihedral angles of
      17.08 (8) and 8.63 (7) degrees  in mol-ecules A and B, respectively.

PMID- 22969576
TI  - 1,4-Dibromo-2,5-dibut-oxy-benzene.
AB  - The asymmetric unit of the title compound, C(14)H(20)Br(2)O(2), contains one half
      mol-ecule located on an inversion centre. The mol-ecule is essentially planar,
      with a maximum deviation from the best plane of the non-H atoms of 0.054 (2) A
      for the O atoms. The but-oxy group adopts a fully extended all-trans
      conformation. In the crystal, mol-ecules are connected via C-Br?O halogen bonds
      [Br?O = 3.2393 (19) A] into a two-dimensional corrugated network in the bc plane.

PMID- 22969577
TI  - (E)-1-(2,4-Dinitro-phen-yl)-2-[1-(3-nitro-phen-yl)ethyl-idene]hydrazine.
AB  - In the asymmetric unit of the title compound, C(14)H(11)N(5)O(6), there are three
      crystallographically independent mol-ecules with similar conformations but some
      differences in bond angles. The mol-ecules are slightly twisted with the dihedral
      angles between the benzene rings being 10.02 (14), 8.41 (15) and 1.40 (14)
      degrees . In each mol-ecule, an intra-molecular N-H?O hydrogen bond generates an
      S(6) ring motif. In the crystal, mol-ecules are linked by weak C-H?O inter
      actions into a three-dimensional network. pi-pi inter-actions with centroid
      centroid distances of 3.5635 (17)-3.8273 (18) A are observed.

PMID- 22969579
TI  - 2-[(E)-({4-[(4,6-Dimethyl-pyrimidin-2-yl)sulfamo-yl]phen-yl}iminio)meth-yl]-6-hy
      droxy-phenolate.
AB  - The title compound, C(19)H(18)N(4)O(4)S, exists as a zwitterion in the solid
      state, with nominal proton transfer from a phenol group to the imine N atom. The
      2,3-dihy-droxy-benzaldehyde fragment is oriented at a dihedral angle of 35.51
      (11) degrees  to the adajacent aniline group and makes a dihedral angle of 76.99
      (6) degrees  with the 4,6-dimethyl-pyrimidin-2-amine group. Intra-molecular O-H?O
      and N-H?O hydrogen bonds close S(5) and S(6) rings, respectively; the same O atom
      accepts both bonds. In the crystal, polymeric chains along [001] are formed from
      mol-ecules joined end-to-end by N-H?O and O-H?N hydrogen bonds; these feature
      R(2) (3)(6) loops. The polymeric chains are linked by C-H?O inter-actions and
      there are pi-pi inter-actions between the pyrimidine rings with a centroid
      centroid distance of 3.446 (2) A.

PMID- 22969578
TI  - 2-Hy-droxy-N'-methyl-benzohydrazide.
AB  - In the title mol-ecule, C(8)H(10)N(2)O(2), there is an intra-molecular hydrogen
      bond involving the hy-droxy group and the O atom of the carbonyl group. The
      dihedral angle between the benzene ring and the amide fragment is 87.16 (10)
      degrees . The C-N-N-C torsion angle is 88.87 (18) degrees . In the crystal, N-H?N
      and N-H?O hydrogen bonds connect mol-ecules into chains along [100]. In addition,
      there is a weak C-H?pi inter-action.

PMID- 22969580
TI  - Bis(pyrrolidin-1-yl)phosphinic (2,4-di-fluoro-benzo-yl)amide.
AB  - The P atom in the title mol-ecule, C(15)H(20)F(2)N(3)O(2)P, is in a distorted
      tetra-hedral P(O)(N)(N)(2) environment. The phosphoryl group and the NH unit
      adopt a syn orientation with respect to each other. An F atom at position 2 and
      an H atom at position 6 are found to occupy similar sites in a 0.70:0.30 ratio
      and were refined with fixed occupancies. The pyrrolidin-1-yl rings are disordered
      over two sets of sites, with site occupancies of 0.566 (6) and 0.434 (6), and
      were refined using a two-part model. In the crystal, hydrogen-bonded dimers
      linked by pairs of N-H?O(P) hydrogen bonds generate an R(2) (2)(8) ring motif.

PMID- 22969581
TI  - 4-Bromo-1H-pyrrole-2-carb-oxy-lic acid.
AB  - In the title compound, C(5)H(4)BrNO(2), the non-H atoms of the pyrrole ring and
      the Br atom are approximately coplanar, with an r.m.s. deviation from the best
      fit plane of 0.025 (6) A;. The dihedral angle between the plane of the carb-oxy
      group and this plane is 14.1 (2) degrees . In the crystal, O-H?O hydrogen bonds
      link the mol-ecules together, forming corrugated sheets parallel to the bc plane.

PMID- 22969582
TI  - (4-Ethenylphen-yl)diphenyl-phosphine selenide.
AB  - In the title mol-ecule, C(10)H(17)PSe, the P atom has a distorted tetra-hedral
      environment resulting in an effective cone angle of 165 degrees . The benzene
      ring makes dihedral angles of 70.04 (8) and 77.28 (8) degrees  with the phenyl
      rings, while the dihedral angle between the phenyl rings is 62.95 (8) degrees .
      In the crystal, mol-ecules are linked by C-H?pi inter-actions.

PMID- 22969583
TI  - 5-Methyl-1H-indole-3-carbaldehyde.
AB  - The title mol-ecule, C(10)H(9)NO, is almost planar with an r.m.s. deviation for
      all non-H atoms of 0.0115 A. In the crystal, mol-ecules are connected through N
      H?O hydrogen bonds into chains running along [021]. The chains are further
      connected via C-H?pi inter-actions, forming layers in the bc plane.

PMID- 22969584
TI  - 2-Amino-4-(4-chloro-phen-yl)-5,6,7,8,9,10-hexa-hydro-benzo[8]annulene-1,3
      dicarbonitrile.
AB  - In the title compound, C(20)H(18)ClN(3), the cyclo-octene ring exhibits
      conformational disorder of two methyl-ene groups with a site-occupation factor of
      0.859 (6) for the major occupied site. In the crystal, mol-ecules are connected
      into inversion dimers via pairs of weak N-H?N hydrogen bonds, forming an R(2)
      (2)(12) graph-set motif. These dimers are further connected via weak N-H?Cl inter
      actions into chains running along [011]. There are also C-H?N interactions
      present in the crystal.

PMID- 22969585
TI  - 2,5-Diamino-thio-phene-3,4-dicarbonitrile.
AB  - In the title compound, C(6)H(4)N(4)S, the planar mol-ecule lies across a
      crystallographic mirror plane. In the crystal, the mol-ecules form
      centrosymmetric dimers through cyclic amino N-H?N hydrogen-bonding associations
      with cyano N-atom acceptors [graph set R(2) (2)(12)] and these dimers are
      extended through amine-cyano N-H?N associations into a three-dimensional network.

PMID- 22969586
TI  - 4-{(E)-2-[4-(Diethyl-amino)-phen-yl]ethen-yl}-1-methyl-pyridin-1-ium tetra-phenyl
      borate.
AB  - In the cation of the title salt, C(18)H(23)N(2) (+).C(24)H(20)B(-), the pyridine
      ring forms a dihedral angle of 14.23 (6) degrees  with the benzene ring. One of
      the ethyl groups of the cation was refined as disordered over two sets of sites
      with equal occupancies.

PMID- 22969587
TI  - 1-[(4-Chloro-phen-yl)(phen-yl)meth-yl]piperazine-1,4-diium bis-(trichloro
      acetate)-trichloro-acetic acid (1/1).
AB  - In the title salt adduct, C(17)H(21)ClN(2) (2+).2C(2)Cl(3)O(2) (
      ).C(2)HCl(3)O(2), the Cl atom of the dication is disordered over two positions in
      a 0.915 (3):0.085 (3) ratio. The Cl atoms in the trichloroacetate anions and
      trichloroacetic acid molecule are also disordered, with refined site-occupation
      factors of 0.59 (3):0.41 (3), 0.503 (12):0.417 (12) and 0.653 (12):0.347 (12).
      The piperazine ring adopts a chair conformation, with puckering parameters Q(T) =
      0.587 (3) A, theta = 2.6 (2) and Phi 334 (6) degrees . In the crystal,
      neighbouring mol-ecules are linked by N-H?O, O-H?O, N-H?Cl, C-H?O and C-H?Cl
      hydrogen bonds, forming a three-dimensional network.

PMID- 22969588
TI  - 2-Meth-oxy-imino-2-{2-[(2-methyl-phen-oxy)meth-yl]phen-yl}ethanol.
AB  - In the title compound, C(17)H(19)NO(3), the dihedral angle between the benzene
      rings is 68.0 (1) degrees . The C-O-C-C torsion angle of the atoms joining these
      rings is 179.7 (2) degrees . The atoms of the methanol group were refined as
      disordered over two sets of sites with fixed occupancies of 0.86 and 0.14. The H
      atoms of the hy-droxy group in the major component are disordered over a further
      two sets of sites with equal occupancies. This is a necessary arrangement to
      allow for hydrogen bonding without unrealistic H?H contacts. In the crystal, O
      H?N and O-H?O hydrogen bonds connect mol-ecules into chains along [001].

PMID- 22969589
TI  - (E)-4-Hy-droxy-N'-(2-hy-droxy-5-iodo-benzyl-idene)benzohydrazide methanol
      monosolvate.
AB  - In the title compound, C(14)H(11)IN(2)O(3).CH(4)O, the dihedral angle between the
      benzene rings is 33.2 (3) degrees . The mol-ecule displays trans and anti
      conformations about the C=N and N-N bonds, respectively. There is an intra
      molecular O-H?N(azomethine) hydrogen bond. Inter-molecular N-H?O and O-H?O
      hydrogen bonds consolidate mol-ecules into a three-dimensional architecture.

PMID- 22969590
TI  - 2,6-Diacetyl-pyridine-resorcinol (1/1).
AB  - The title co-crystal, C(9)H(9)NO(2).C(6)H(6)O(2), is composed of one 2,6-diacetyl
      pyridine mol-ecule and one resorcinol mol-ecule as the asymmetric unit. In the
      2,6-diacetyl-pyridine mol-ecule, the two carbonyl groups are anti-periplanar to
      the pyridine N atom. In the crystal, the 2,6-diacetyl-pyridine and resorcinol mol
      ecules are connected by two O-H?O hydrogen bonds, forming planar chains of
      alternating components running along [120].

PMID- 22969591
TI  - 5-Amino-3-(4H-1,2,4-triazol-4-yl)-1H-1,2,4-triazole.
AB  - The asymmetric unit of the title compound, C(4)H(5)N(7), comprises two
      independent but virtually superimposable mol-ecules. Each mol-ecule is planar
      with the dihedral angles between the five-membered rings being 2.8 (3) and 2.1
      (3) degrees . The crystal structure is formed by an extensive network of
      relatively strong N-H?N hydrogen-bond inter-actions. Individual mol-ecules are
      arranged into supra-molecular zigzag chains running parallel to [001] by way of
      the strongest N-H?N inter-actions. Adjacent chains are inter-connected by rather
      long (D?A distances range from ca 3.00 to 3.03 A) but highly directional (inter
      action angles above ca 173 degrees ) hydrogen bonds forming a supra-molecular
      layer in the bc plane.

PMID- 22969592
TI  - N-(2-Benzoyl-eth-yl)propan-2-aminium chloride.
AB  - In the title salt, C(12)H(18)NO(+).Cl(-), N-H?Cl inter-actions between the free
      chloride anions and the organic cations connect the mol-ecules into hydrogen-bond
      dimers, forming a R(2) (2)(8) motif. The dimers are linked by C-H?O hydrogen
      bonds into chains extending along [301]. The carbonyl group is co-planar with the
      phenyl ring [C-C-C=O torsion angle = -3.3 (7) degrees ]. The side chain has an E
      conformation.

PMID- 22969593
TI  - N-(2,4-Dichloro-phen-yl)-1,3-thia-zol-2-amine.
AB  - In the title mol-ecule, C(9)H(6)Cl(2)N(2)S, the mean planes of the benzene and
      thia-zole rings make a dihedral angle of 54.18 (8) degrees . In the crystal, mol
      ecules are joined into dimers with an R(2) (2)(8) ring motif by pairs of N-H?N
      hydrogen bonds. These dimers are linked by C-H?Cl inter-actions into layers
      parallel to (011). The thia-zole rings form columns along the c-axis direction,
      with a centroid-centroid separation of 3.8581 (9) A, indicating pi-pi inter
      actions. An intra-molecular C-H?S contact also occurs.

PMID- 22969594
TI  - (Z)-2-Benzyl-idenebenzo[d]thia-zolo[3,2-a]imidazol-3(2H)-one.
AB  - The mol-ecule of the title compound, C(16)H(10)N(2)OS, is approximately planar,
      the dihedral angle between the 1,3-benzothia-zolo[3,2-a]imidazol-3(2H)-one and
      the benzyl-idene moieties being 4.10 (8) degrees . A weak intra-molecular C-H?S
      inter-action generates an S(6) ring. No inter-molecular hydrogen bonds are
      observed in the crystal structure.

PMID- 22969595
TI  - N-[2-(4-Methyl-benzo-yl)eth-yl]propan-2-aminium chloride.
AB  - In the title compound, C(13)H(20)NO(+).Cl(-), the protonated amino N atom is
      hydrogen bonded to the chloride anion. N-H?Cl hydrogen bonds link the anions and
      cations into dimers, which are connected by C-H?O hydrogen bonds, forming supra
      molecular chains extending along [100].

PMID- 22969596
TI  - 2-(4-Fluoro-phen-yl)-1-phenyl-1H-benzimidazole.
AB  - In the title mol-ecule, C(19)H(13)FN(2), the benzimidazole unit is close to
      planar [maximum deviation = 0.0342 (9) A] and forms dihedral angles of 58.94 (3)
      and 51.43 (3) degrees  with the phenyl and fluoro-benzene rings, respectively;
      the dihedral angle between the phenyl and fluoro-benzene rings is 60.17 (6)
      degrees . In the crystal, three C-H?F hydrogen bonds and two weak C-H?pi inter
      actions involving the fused benzene ring lead to a three-dimensional
      architecture.

PMID- 22969597
TI  - N'-[(E)-(3-Fluoro-pyridin-2-yl)methyl-idene]benzohydrazide monohydrate.
AB  - The title compound, C(13)H(10)FN(3)O.H(2)O, exists in the E conformation with
      respect to the azomethane C=N double bond. The mol-ecule is close to planar with
      a maximum deviation of 0.286 (2) A. The pyridine ring is essentially coplanar
      with the central C(= O)N(2)C unit [dihedral angle = 2.02 (3) degrees ] and the
      phenyl ring exhibits a dihedral angle of 14.41 (10) degrees  with respect to the
      central unit. The crystal structure features O-H?N, N-H?O and O-H?O hydrogen-bond
      inter-actions between the solvent water and the benzohydrazide mol-ecules, as
      well as C-H?O hydrogen bonds and C-F?pi [3.0833 (18) A] inter-actions.

PMID- 22969598
TI  - N,N,N',N'-Tetra-methyl-phthalamide.
AB  - The title compound, C(12)H(16)N(2)O(2), crystallized from toluene with two
      independent mol-ecules in the asymmetric unit. The dihedral angles between the
      amide groups and the benzene ring are 60.87 (11) and 54.08 (11) degrees  in one
      independent molecule and 60.13 (11) and 64.64 (11) in the other. The crystal
      structure features weak C-H?O hydrogen bonds and C-H?pi inter-actions.

PMID- 22969599
TI  - 6,6'-Dimeth-oxy-2,2'-{[(E,E)-hydrazine-1,2-diyl-idene]bis-(methanylyl
      idene)}diphenol methanol disolvate.
AB  - The title compound, C(16)H(16)N(2)O(4).2CH(3)OH, is a hydrazone in an E geometric
      arrangement, with an inversion centre at the mid-point of the N-N bond. A
      symmetry-related pair of six-membered hydrogen-bonded rings [graph-set motif S(1)
      (1)(6)] are present for the terminal vanillin-imine moieties. Two lattice
      methanol solvent mol-ecules are present per formula unit (Z' = 1/2), which form
      hydrogen-bonded chains along [010] with two orientations due to disorder of the
      methanol H-atom.

PMID- 22969600
TI  - (20S)-Dammar-24-ene-3beta,20-diol monohydrate from the bark of Aglaia exima
      (Meliaceae).
AB  - In the title compound {systematic name: (1R,2R,5R,7R,10R,11R,14S,15R)-14-[(2S)-2
      hy-droxy-6-methyl-hept-5-en-2-yl]-2,6,6,10,11-penta-methyl-tetra-cyclo
      [8.7.0.0(2,7).0(11,15)]hepta-decan-5-ol monohydrate}, C(30)H(52)O(2).H(2)O, the
      three fused cyclo-hexane rings adopt chair conformations and the hy-droxy
      substituent of one of these occupies an axial position. The fused cyclo-pentane
      ring adopts an envelope conformation (with the flap atom being the C atom bearing
      the methyl group) and the 3-methyl-but-2-enyl portion of its substituent is
      disordered over three sets of sites in a 0.413 (7):0.250 (7):0.337 (7) ratio. The
      O atoms of both water mol-ecules occupy special positions of 2 site symmetry. In
      the crystal, O(s)-H?O(w) and O(w)-H?O(s) (s = steroid and w = water) hydrogen
      bonds link hy-droxy groups and water mol-ecules, forming a three-dimensional
      network. The crystal studied was found to be a non-merohedral twin with a 0.518
      (1):0.482 (1) component ratio.

PMID- 22969601
TI  - 2,3,3-Trimethyl-1-[4-(2,3,3-trimethyl-3H-indol-1-ium-1-yl)but-yl]-3H-indol-1-ium
      diiodide.
AB  - In the crystal of the title salt, C(26)H(34)N(2) (2+).2I(-), the dication lies on
      a center of inversion that exists along the mid-point of the butyl chain; its
      five-membered ring is approximately planar (r.m.s. deviation = 0.011 A). In the
      crystal, the iodide anion is disordered over two positions in a 1:1 ratio.

PMID- 22969602
TI  - Ethyl 1-phenyl-2-[4-(trifluoro-meth-oxy)phen-yl]-1H-benzimidazole-5-carboxyl-ate.
AB  - In the title compound, C(23)H(17)F(3)N(2)O(3), an intra-molecular C-H?F hydrogen
      bond generates an S(6) ring motif. The essentially planar 1H-benzimidazole ring
      system [maximum deviation = 0.021 (2) A] forms dihedral angles of 25.00 (10) and
      62.53 (11) degrees  with the trifluoro-meth-oxy-substituted benzene and phenyl
      rings, respectively. The twist of the ethyl acetate group from the least-squares
      plane of the 1H-benzimidazole ring system is defined by a C(=O)-O-C-C torsion
      angle of 79.5 (3) degrees . In the crystal, mol-ecules are linked into a two
      dimensional network parallel to the bc plane by weak C-H?N and C-H?O hydrogen
      bonds. Weak C-H?pi inter-actions also observed.

PMID- 22969603
TI  - 6-Bromo-1-methyl-4-[2-(4-nitro-benzyl-idene)hydrazin-1-yl-idene]-2,2-dioxo-3,4
      dihydro-1H-2lambda(6),1-benzothia-zine.
AB  - In the title compound, C(16)H(13)BrN(4)O(4)S, the dihedral angle between the
      aromatic rings is 4.1 (2) degrees  and the C=N-N=C torsion angle is 175.5 (3)
      degrees . The nitro group is almost coplanar with the benzene ring to which it is
      attached [dihedral angle = 2.9 (7) degrees ]. The thia-zine ring has an S
      envelope conformation with the S atom displaced by 0.819 (3) A from the mean
      plane of the other five atoms (r.m.s. deviation = 0.017 A). In the crystal, C-H?O
      inter-actions link the mol-ecules and weak aromatic pi-pi stacking [centroid
      centroid separation = 3.874 (2) A] is also observed.

PMID- 22969604
TI  - 1-{[Dimeth-yl(phen-yl)sil-yl]meth-yl}-3-(2-phenyl-eth-yl)-1H-benzimidazol-3-ium
      bromide monohydrate.
AB  - The title compound, C(24)H(27)N(2)Si(+).Br(-).H(2)O, was synthesized from 1
      (dimethyl-phenyl-silylmeth-yl)-1H-benzimidazole and (2-bromo-eth-yl)benzene in
      dimethyl-formamide. The benzimidazole ring system is nearly planar, with a
      maximum deviation of 0.015 (5) A, and forms dihedral angles of 73.0 (3) and 39.6
      (2) degrees , with the phenyl rings. In the crystal, mol-ecules are linked by O
      H?Br, C-H?Br and C-H?O hydrogen bonds. In addition, the structure features pi-pi
      stacking inter-actions, with a face-to-face separation of 3.644 (3) A between
      parallel benzimidazole ring systems.

PMID- 22969605
TI  - 1-[4-(4-Chloro-phen-yl)piperazin-1-yl]-3-(6-oxo-3,4-diphenyl-1,6-dihydro
      pyridazin-1-yl)propan-1-one.
AB  - In the title compound, C(29)H(27)ClN(4)O(2), the six-membered ring of the
      pyridazine group is nearly planar [maximum deviation = -0.062 (2) A] and its mean
      plane makes dihedral angles of 43.05 (9), 44.71 (10) and 72.57 (9) degrees ,
      respectively, with the two phenyl and benzene rings. The piperazine ring has a
      chair conformation and its mean plane is almost perpendicular to the attached
      benzene ring, with a dihedral angle of 83.20 (16) degrees . In the crystal, mol
      ecules are linked via two pairs of C-H?O inter-actions, which result in the
      formation of chains propagating along [10-1]. Neighbouring chains are linked via
      C-H?pi inter-actions.

PMID- 22969606
TI  - 2-[7-(3,5-Dibromo-2-hy-droxy-phen-yl)-6-eth-oxy-carbonyl-2-oxo-5H-2,3,6,7-tetra
      hydro-thio-pyrano[2,3-d][1,3]thia-zol-6-yl]acetic acid ethanol monosolvate.
AB  - The title compound, C(17)H(15)Br(2)NO(6)S(2).C(2)H(5)OH, is the esterification
      reaction product of 2-(8,10-dibromo-2,6-dioxo-3,5,5a,11b-tetra-hydro-2H,6H
      chromeno[4',3':4,5]thio-pyrano[2,3-d]thia-zol-5a-yl)acetic acid. Cleavage of the
      lactone ring and formation of eth-oxy-carbonyl and hy-droxy groups from its
      structural elements were observed. On the other hand, the carb-oxy-methyl group
      was not esterified. The H atom and carb-oxy-methyl group, both at stereogenic
      centres, show a cis conformation. The six-membered dihydro-thio-pyran ring adopts
      a half-chair conformation. All NH and OH groups participate in the three
      dimensional hydrogen-bond network, which is additionally strengthened by C-H?O
      and C-H?S inter-actions. Intramolecular O-H?Br and C-H?O interactions also occur.

PMID- 22969607
TI  - 2,3,6-Trichloro-5-(trichloro-meth-yl)pyridine.
AB  - The title compound, C(6)HCl(6)N, lies on a mirror plane, the asymmetric unit
      conataining a half-mol-ecule. Weak intra-molecular C-H?Cl contacts are observed.

PMID- 22969608
TI  - (2E)-3-[4-(Benz-yloxy)phen-yl]-1-(pyridin-3-yl)prop-2-en-1-one.
AB  - The title compound, C(21)H(17)NO(2), exists in an E conformation with respect to
      the C=C bond. The pyridine ring forms dihedral angles of 5.57 (7) and 82.30 (9)
      degrees , respectively, with the central benzene ring and the terminal phenyl
      ring. The dihedral angle between the benzene and phenyl rings is 87.69 (8)
      degrees . No significant inter-molecular inter-actions are observed.

PMID- 22969609
TI  - 1-(1,5-Diphenyl-4-phenyl-sulfonyl-1H-pyrazol-3-yl)ethanone.
AB  - The asymmetric unit of the title compound, C(23)H(18)N(2)O(3)S, contains two mol
      ecules with comparable geometries. In one mol-ecule, the pyrazole ring forms
      dihedral angles of 61.65 (11), 47.88 (11) and 63.20 (14) degrees  with the three
      benzene rings. The corresponding values for the other mol-ecule are 77.19 (11),
      43.55 (11) and 63.56 (15) degrees . In the crystal, both mol-ecules are linked
      into inversion dimers by pairs of C-H?S hydrogen bonds, generating R(2) (2)(14)
      loops in each case.

PMID- 22969610
TI  - 3-Oxo-3-(piperidin-1-yl)propane-nitrile.
AB  - In the title compound, C(8)H(12)N(2)O, the piperidine ring exhibits a chair
      conformation and its least-squares plane (all atoms) makes a dihedral angle of
      32.88 (12) degrees  with the propane-nitrile unit (r.m.s. deviation = 0.001 A).
      In the crystal, mol-ecules are linked by C-H?O hydrogen bonds, forming chains
      along [001].

PMID- 22969611
TI  - (Z)-2-(5-Acetyl-4-methyl-3-phenyl-2,3-dihydro-1,3-thia-zol-2-yl-idene)-3-(3
      methyl-1-benzofuran-2-yl)-3-oxo-propane-nitrile.
AB  - In the title compound, C(24)H(18)N(2)O(3)S, the benzofuran ring system (r.m.s.
      deviation = 0.010 A) forms dihedral angles of 83.13 (17) and 8.92 (14) degrees 
      with the benzene and thia-zole rings, respectively. The dihedral angle between
      the benzene and thia-zole rings is 84.51 (19) degrees . The mol-ecular structure
      features an intra-molecular C-H?O hydrogen bond, which closes an S(6) ring. There
      are no inter-molecular hydrogen bonds observed in this structure.

PMID- 22969612
TI  - (E)-2-[4-(Diethyl-amino)-styr-yl]-1-methyl-pyridinium 4-meth-oxy-benzene
      sulfonate monohydrate.
AB  - In the cation of the title compound, C(18)H(23)N(2) (+).C(7)H(7)O(4)S(-).H(2)O,
      one ethyl group of the diethyl-amino unit is disordered over two sets of sites in
      a 0.665 (6):0.335 (6) ratio. The styrylpyridinium unit is nearly planar, with a
      dihedral angle between the pyridinium and benzene rings of 4.27 (8) degrees . In
      the crystal, the anion ring is almost perpendicular to the aromatic rings of the
      cation; the sulfonate-substituted benzene ring forms dihedral angles of 89.60 (8)
      and 89.37 (8) degrees , respectively, with the pyridinium and benzene rings of
      the cation. In the crystal, the three components are linked into a three
      dimensional network by O-H?O and C-H?O hydrogen bonds. pi-pi inter-actions with
      centroid-centroid distances of 3.6999 (9) and 3.7106 (9) A are also present.

PMID- 22969613
TI  - 4-Bromo-2-{(E)-[(3,4-dimethyl-phen-yl)imino]-meth-yl}phenol.
AB  - In the title compound, C(15)H(14)BrNO, the dihedral angle between the aromatic
      rings is 4.10 (11) degrees  and the mol-ecule is close to planar (r.m.s.
      deviation for the non-H atoms = 0.053 A). An intra-molecular O-H?N hydrogen bond
      closes an S(6) ring. In the crystal, very weak C-H?pi inter-actions are observed.

PMID- 22969614
TI  - (2Z)-N-(2-Chloro-benz-yl)-2-(2-oxo-2,3-dihydro-1H-indol-3-yl
      idene)hydrazinecarbothio-amide.
AB  - In the title compound, C(16)H(13)ClN(4)OS, the isatin ring system is oriented at
      dihedral angles of 10.60 (7) and 72.60 (3) degrees  with respect to the thio
      semicarbazide and 2-chloro-benzyl groups, respectively. The near planarity of the
      isatin and thio-semicarbazide groups [r.m.s. deviations of 0.0420 and 0.0163 A,
      respectively] is reinforced by intra-molecular N-H?O and N-H?N hydrogen bonds,
      which generate S(6) and S(5) rings, respectively. In the crystal, inversion
      dimers linked by pairs of N-H?O hydrogen bonds generate R(2) (2)(8) loops.
      Aromatic pi-pi stacking inter-actions between the centroids of heterocyclic five
      membered and benzene rings [distance = 3.6866 (11) A] are also observed.

PMID- 22969615
TI  - 1'-Benzylspiro-[chromene-2,4'-piperi-dine]-4-carbonitrile.
AB  - In the title compound, C(21)H(20)N(2)O, the piperidine ring adopts a chair
      conformation while the pyran ring adopts a screw-boat conformation. The
      piperidine ring forms dihedral angles of 65.75 (3) and 67.79 (5) degrees  with
      the chroman and methyl-substituted benzene rings, respectively. The crystal
      structure features weak C-H?pi and pi-pi [centroid-centroid distance = 3.8098 (8)
      A] inter-actions.

PMID- 22969616
TI  - 4-Carbamoylpyridin-1-ium 2,2,2-trichloro-acetate.
AB  - In the asymmetric unit of the title salt, C(6)H(7)N(2)O(+).C(2)Cl(3)O(2) (-),
      there are two crystallographic independent ion pairs. The amide groups of the 4
      carbamoylpyridin-1-ium ions are slightly twisted out of the plane of the aromatic
      ring with C-C-C-N torsion angles of 8.8 (9) degrees  and 4.6 (8) degrees . In the
      crystal, the 4-carbamoylpyridin-1-ium ion is N-H?O hydrogen bonded to the
      trichloro-acetate ion via the pyridinium unit and amide group. Layers parallel to
      the ac plane are formed due to the N-H?O hydrogen bonding of the adjacent amide
      groups of 4-carbamoylpyridin-1-ium ions. Weak C-H?O inter-actions also occur.

PMID- 22969617
TI  - 3,3'-(Ethane-1,2-diyl)bis(6-meth-oxy-3,4-dihydro-2H-1,3-benzoxazine) mono
      hydrate.
AB  - The asymmetric unit of the title compound, C(20)H(24)N(2)O(4).H(2)O, contains one
      half-organic mol-ecule (an inversion centre generates the other half of the mol
      ecule) and a half-mol-ecule of water (the O atom has site symmetry 2). The near
      planarity of the fused-benzene ring is illustrated by the very small deviations
      of all the atoms from the plane [largest deviation = 0.0092 (11) A. The six
      membered N,O-containing ring adopts a half-chair conformation. The observed N
      CH(2) and CH(2)-O bond lengths can be correlated to the manifestation of an
      anomeric effect in the N-CH(2)-O unit. In the crystal, the mol-ecules are
      connected into zigzag chains parallel to [001] through O-H?N hydrogen bonds
      formed between the oxazinic N atom and the solvent water mol-ecule. The chains
      are consolidated by C-H?O inter-actions.

PMID- 22969618
TI  - 3-Allyl-1-methyl-1H-benzotriazol-3-ium iodide.
AB  - In the crystal structure of 1-methyl-3-allyl benzotriazolium iodide,
      C(10)H(12)N(3) (+).I(-), centrosymmetric dimers of coplanar cations are pi
      stacked with an inter-planar distance of 3.453 (6) A. The iodide anions are
      situated above and below the formally positive charged triazolium rings.

PMID- 22969619
TI  - 3-(Phenyl-carbamoyl)acrylic acid.
AB  - In the title compound, C(10)H(9)NO(3), the dihedral angle between the phenyl ring
      and the amide group is 10.8 (2) degrees . The C=O and O-H bonds of the carboxyl
      group adopt an anti orientation and an intra-molecular O-H?O hydrogen bond closes
      an S(7) ring. In the crystal, N-H?O hydrogen bonds link the mol-ecules into C(7)
      chains propagating in [101]. The packing is consolidated by C-H?O inter-actions,
      generating sheets aligned at an angle of ca 60 degrees  with the bc plane.

PMID- 22969620
TI  - (2E,4R,5R,6S)-2-(4,5,6-Trihy-droxy-cyclo-hex-2-en-1-yl-idene)acetonitrile.
AB  - The crystal structure of the title compound, C(8)H(9)NO(3), is characterized by a
      complex three-dimensional hydrogen-bond network in which every mol-ecule is
      connected to six symmetry-related neighbours.

PMID- 22969621
TI  - Pyrrolidine-2,5-dione.
AB  - In the title compound, C(4)H(5)NO(2), the non-H atoms are nearly coplanar, with a
      maximum deviation of 0.030 (1) A. In the crystal, pairs of mol-ecules are linked
      by N-H?O hydrogen bonds into inversion dimers.

PMID- 22969622
TI  - N,N'-(4,5-Dimethyl-1,2-phenyl-ene)bis-(pyridine-2-carboxamide).
AB  - In the title compound, C(20)H(18)N(4)O(2), the dihedral angles between the
      central benzene ring and the pyridine rings are 57.55 (6) and 22.05 (8) degrees .
      The mol-ecular conformation is stabilized by intra-molecular N-H?N inter-actions
      and in the crystal structure an inter-molecular asymmetric cyclic hydrogen
      bonding association involving both amide N-H donors and a common amide O-atom
      acceptor gives a chain extending along the c axis.

PMID- 22969623
TI  - 3,5,6-Trimethyl-thieno[2,3-d]pyrimidin-4(3H)-one.
AB  - In the title compound, C(9)H(10)N(2)OS, the thienopyrimidine ring system is
      almost planar [greatest deviation from the mean plane = 0.0318 (13) A for the S
      atom]. The crystal packing features C-H?O hydrogen bonds and pi-pi stacking inter
      actions between inversion-related pairs of mol-ecules with a centroid-centroid
      distance of 3.530 (3) A.

PMID- 22969624
TI  - (1E,2E)-1,2-Bis(2,3-dihydro-1H-inden-1-yl-idene)hydrazine.
AB  - In the title compound, C(18)H(16)N(2), there are two independent half-mol-ecules
      (A and B) in the asymmetric unit, each mol-ecule being completed by an inversion
      center situated in the mid-point of the central N-N bond. The mol-ecules
      themselves therefore are essentially planar with r.m.s. deviations of 0.015 (1)
      and 0.020 (1) A, respectively. In the crystal, mol-ecules are connected via C
      H?pi inter-actions in which only type B mol-ecules are donors, while both A and B
      mol-ecules act as acceptors. As a result, type B mol-ecules are linked into
      infinite chains along b, which are inter-connected by molecules of type A.

PMID- 22969625
TI  - 3-(2-Fluoro-phenyl-sulfin-yl)-2,4,5,6-tetra-methyl-1-benzofuran.
AB  - In the title compound, C(18)H(17)FO(2)S, the 2-fluoro-phenyl ring makes a
      dihedral angle of 85.45 (4) degrees  with the mean plane [r.m.s. deviation =
      0.017 (1) A] of the benzofuran fragment. In the crystal, mol-ecules are linked by
      weak C-H?O and C-H?pi inter-actions.

PMID- 22969626
TI  - Bis(2,6-dimethyl-pyridinium) dibromo-iodate bromide.
AB  - In the title salt, 2C(7)H(10)N(+).IBr(2) (-).Br(-), each of the anions, viz.
      [IBr(2)](-) and Br(-), lie on a twofold axis. The IBr(2) (-) anion is almost
      linear, with a Br-I-Br angle of 178.25 (3) degrees . The cation is essentially
      planar (r.m.s. deviation = 0.0067 A). In the crystal, each Br(-) anion links two
      cations via N-H?Br?H-N hydrogen-bonding inter-actions.

PMID- 22969627
TI  - 2,2'-{[2-(Pyridin-2-yl)-1,3-diazinane-1,3-diyl]bis(methylene)}diphenol.
AB  - The title compound, C(23)H(25)N(3)O(2), was obtained as an inter-mediary in the
      preparation of non-symmetric tertiary diamines. The mol-ecular structure presents
      T-shaped spatial form, in which the pyrimidine ring exhibits a chair
      conformation. The pyridyl ring is almost perpendicular to the phenyl rings with
      dihedral angles of 80.17 (8) and 76.03 (2) degrees . The phenol and amine groups
      are involved in two strong intra-molecular O-H?N inter-actions. In the crystal,
      the mol-ecules are stacked along [010]; however, no inter-molecular inter-actions
      are observed.

PMID- 22969628
TI  - N-(4-Methyl-phen-yl)-2-nitro-benzene-sulfonamide.
AB  - In the crystal of the title compound, C(13)H(12)N(2)O(4)S, the conformation of
      the N-H bond in the -SO(2)-NH- segment is syn to the ortho-nitro group in the
      sulfonyl benzene ring. The mol-ecule is twisted at the S-N bond with a torsion
      angle of 76.55 (18) degrees . The dihedral angle between the planes of the rings
      is 72.64 (8) degrees . In the crystal, mol-ecules are linked by pairs of N-H?O(S)
      hydrogen bonds to form inversion dimers.

PMID- 22969629
TI  - 11-(4-Methyl-phen-yl)-8,9-dihydro-7H-benzo[f]cyclo-penta-[b]quinolin-10(11H)-one.
AB  - In the title compound, C(23)H(19)NO, the naphthalene ring system and the cyclo
      pent-2-enone ring exhibit planar conformations with maximum deviations of 0.034
      (1) and 0.02 (1) A, respectively. The 1,4-dihydro-pyridine ring adopts an
      envelope conformation with the C atom bearing the p-tolyl ring as the flap atom.
      Inter-molecular N-H?O hydrogen bonds and C-H?pi inter-actions stabilize the
      crystal packing.

PMID- 22969630
TI  - (2S,4S)-3-Benzoyl-4-benzyl-2-tert-but-yl-1,3-oxazolidin-5-one.
AB  - In the title compound, C(21)H(23)NO(3), the central oxazolidinone ring is
      approximately planar, the maximum deviation from the plane through the central
      ring being 0.043 (1) A. The tert-butyl and benzyl substituents are cis to each
      other and trans to the N-benzoyl group. The inter-planar angle between the
      aromatic rings of the C-benzyl and N-benzoyl groups is 81.10 (4) degrees .

PMID- 22969631
TI  - 2,5-Dichloro-N-(2,3-dimethyl-phen-yl)benzene-sulfonamide.
AB  - In the title compound, C(14)H(13)Cl(2)NO(2)S, the dihedral angle between the
      aromatic rings is 62.21 (7) degrees  and the C-S-N-C group adopts a gauche
      conformation [torsion angle = 60.22 (17) degrees ]. In the crystal, N-H?O
      hydrogen bonds link the mol-ecules into C(4) chains propagating in [010]. A short
      inter-molecular Cl?O contact of 3.1115 (17) A is seen.

PMID- 22969632
TI  - 2-Amino-5-(4-carboxyl-atophen-yl)-pyridinium monohydrate.
AB  - The title compound, C(12)H(10)N(2)O(2).H(2)O, crystallizes as a zwitterion in
      which the pyridine N atom is protonated and the carb-oxy -OH group is
      deprotonated. The benzene and pyridinium rings are inclined with a dihedral angle
      of 6.63 (5) degrees  between them. In the crystal, inter-molecular O-H?O and N
      H?O hydrogen-bonding inter-actions link adjacent mol-ecules into a two
      dimensional double layered supra-molecular network.

PMID- 22969633
TI  - (E)-1-Phenyl-3-[4-(trifluoro-meth-yl)phen-yl]prop-2-en-1-one.
AB  - In the title compound, C(16)H(11)F(3)O, the dihedral angle between the two rings
      is 48.8 (2) degrees . The crystal packing exhibits no classical inter-molecular
      inter-actions between the mol-ecules.

PMID- 22969634
TI  - 2,6-Diamino-pyridinium dihydrogen phosphate.
AB  - In the crystal structure of the title compound, C(5)H(8)N(3) (+).H(2)PO(4) (-), N
      H?O hydrogen bonds, involving the unprotonated amino-group and the NH(+) group in
      the pyridinium ring and dihydrogenphosphate O atoms, link the cations and anions.
      A long chain-like stacking of dihydrogenphosphate anions along the c-axis
      direction is constructed by O-H?O hydrogen bonds. Also along the c-axis
      direction, pi-pi stacking between inversion-related pyridinium rings [centroid
      centroid distance = 3.8051 (10) A] forms columnar stacks of cations.

PMID- 22969635
TI  - Benzyl 3-[(E)-(furan-2-yl)methyl-idene]-2-methyldithio-carbazate.
AB  - In the title compound, C(14)H(14)N(2)OS(2), the furan ring exhibits rotational
      disorder over two orientations, with an occupancy ratio of 0.508 (7):0.492 (7).
      The furan and phenyl rings form dihedral angles of 8.2 (6) (major occupancy
      component), 14.8 (6) (minor occupancy component) and 73.65 (9) degrees ,
      respectively, with the central residue (C(4)N(2)S(2)), indicating a twisted
      conformation for the mol-ecule. The methyl group and the thione S atom are syn
      and the conformation about the imine bond is E. In the crystal, C-H?pi inter
      actions involving the phenyl ring are observed.

PMID- 22969636
TI  - 2-{[2,2-Bis(diethyl-amino)-ethan-2-ylium-thio-yl]sulfan-yl}-1,1-bis-(diethyl
      amino)-ethyl-ium bis-(perchlorate).
AB  - The title salt, C(20)H(42)N(4)S(2) (2+).2ClO(4) (-), was obtained from the
      reaction of bis-(diethyl-amino)-carbeniumdithio-carboxyl-ate,
      (Et(2)N)(2)C(2)S(2), with Fe(ClO(4))(2).6H(2)O in CH(2)Cl(2). The title compound,
      in which one of the S atoms of (Et(2)N)(2)C(2)S(2) is bound to a 1,1-bis-(diethyl
      amino)-ethane moiety, has two carbenium C atoms, and the charge compensation is
      provided by two perchlorate anions. The N(2)C-CS(2) bond length is 1.512 (4) A,
      corresponding to a C-C single bond, and the dihedral angle between N(2)C- and 
      CS(2) planes [72.0 (2) degrees ] is smaller than that of (Et(2)N)(2)C(2)S(2)
      [82.0 (1) degrees ]. The crystal structure features C-H?S hydrogen bonds.

PMID- 22969637
TI  - 10-Benzyl-9-(4-eth-oxy-phen-yl)-3,3,6,6-tetra-methyl-3,4,6,7,9,10-hexa-hydro
      acridine-1,8(2H,5H)-dione.
AB  - In the title compound, C(32)H(37)NO(3), the central dihydro-pyridine ring adopts
      a nearly planar flattened-boat conformation, whereas both cyclo-hexenone rings
      adopt half-chair conformations. The mean and maximum deviations from the mean
      plane of the dihydro-pyridine ring are 0.1252 (9) and 0.188 (1) A, respectively.
      The 4-eth-oxy-phenyl and phenyl rings form dihedral angles of 75.20 (4) and 82.14
      (5) degrees  with the dihydro-pyridine mean plane, respectively.

PMID- 22969638
TI  - Ortho-rhom-bic polymorph of (2E)-2-(2,3-dihydro-1H-inden-1-yl-idene)-2,3-di-hydro
      1H-inden-1-one.
AB  - The title compound, C(18)H(14)O, is polymorphic at 123 K. The ortho-rhom-bic form
      reported herein has two independent mol-ecules in the asymmetric unit, with mol
      ecular volume 313.5 A(3). The previously reported triclinic (P-1) form [Raston &
      Scott (2000 ?). Green Chem., 2, 49-52] has mol-ecular volume 309.6 A(3) at the
      same temperature. All three mol-ecules deviate significantly and systematically
      from the putative C(s) symmetry (delta(r.m.s.) = 0.0265, 0.0256, 0.0497 A).
      Comparison of the two molecules in the orthorhombic polymorph shows that 16 of
      the 19 equivalent pairs of framework atoms have a mirror-image pattern of
      deviations (above/below plane), suggesting that the two are quasi-enanti-omorphs.
      The pattern of deviations in the triclinic form is nearly the same (13 of 19 atom
      pairs) as the ortho-rhom-bic form.

PMID- 22969639
TI  - FK228 from Burkholderia thailandensis MSMB43.
AB  - FK228 [systematic name: (1S,4S,7Z,10S,16E,21R)-7-ethyl-idene-4,21-di(propan-2-yl)
      2-oxa-12,13-dithia-5,8,20,23-tetra-za--bicyclo[8.7.6]tricos-16-ene-3,6,9,19,22
      pentone], C(24)H(36)N(4)O(6)S(2), also known as FR901228, depsipeptide, NSC
      630176, romidepsin, and marketed as Istodax by Celgene Corporation, is
      crystallized from ethyl acetate in P2(1) as compared to the absolute
      configuration of FK228, first crystallized from methanol in P2(1)2(1)2(1)
      [Shigematsu et al. (1994 ?). J. Anti-biot.47, 311-314]. A slight difference is
      observed between the absolute configuration of FK228 and the present structure.
      The molecular structure is stabilized by intramolecular N-H?O hydrogen bonds. In
      the crystal, molecules are linked via N-H?O hydrogen bonds.

PMID- 22969640
TI  - 2-Chloro-N-ethyl-9-isopropyl-9H-purin-6-amine.
AB  - In the title compound, C(10)H(14)ClN(5), the purine ring system is essentially
      planar, with an r.m.s. deviation from the least-squares plane defined by the nine
      constituent atoms of 0.0063 (11) A. In the crystal, mol-ecules are linked by weak
      N-H?N and C-H?pi inter-actions.

PMID- 22969641
TI  - N'-[(E)-2-Hy-droxy-5-iodo-benzyl-idene]-4-methyl-benzene-sulfono-hydrazide.
AB  - In the title mol-ecule, C(14)H(13)IN(2)O(3)S, the dihedral angle between the
      planes of the benzene and toluene rings is 84.3 (3) degrees . The mol-ecule
      displays a trans conformation with respect to the C=N bond. There is an intra
      molecular O-H?N hydrogen bond with the azomethine N atom as acceptor. In the
      crystal, N-H?O hydrogen bonds connect the mol-ecules into chains running along
      the b axis.

PMID- 22969642
TI  - Propan-2-yl 2-(1,1,3-trioxo-2,3-dihydro-1lambda(6),2-benzothia-zol-2-yl)acetate.
AB  - In the title mol-ecule, C(12)H(13)NO(5)S, the benzisothia-zole ring system is
      essentially planar (r.m.s. deviation = 0.0169 A) as is the -C-C(=O)-O-C- sequence
      of atoms in the vicinity of the acetate group (r.m.s. deviation = 0.0044 A). The
      mean plane of these atoms forms a dihedral angle of 88.41 (7) degrees  with the
      benzisothia-zole ring system. In the crystal, weak C-H?O hydrogen bonds involving
      methyl-ene and methyne H atoms form R(4) (3)(20) graph-set motifs.

PMID- 22969643
TI  - N,N-Dicyclo-hexyl-4-nitro-benzamide.
AB  - The title compound, C(19)H(26)N(2)O(3), crystallizes with two independent mol
      ecules in the asymmetric unit which differ in the twist of the phenyl rings with
      respect to the plane of the amide group [the C-C-C-O torsion angles are 121.5 (3)
      and -119.6 (3) degrees  in the two mol-ecules. Both cyclo-hexane rings adopt
      chair conformations. In the crystal, weak C-H?O inter-actions occur. The crystal
      studied was a non-merohedral twin with a minor component of 4.8 (1)%.

PMID- 22969644
TI  - 4-But-oxy-N'-[1-(4-methyl-phen-yl)ethyl-idene]benzohydrazide.
AB  - The mol-ecule of the title compound, C(20)H(24)N(2)O(2), exists in a trans
      conformation with respect to the C=N bond. The dihedral angle between the benzene
      rings is 79.0 (1) degrees . In the crystal, N-H?O hydrogen bonds link the mol
      ecules into chains propagating in [001]. Two weak C-H?O inter-actions also occur.

PMID- 22969645
TI  - Diethyl 3,3'-(phenyl-methyl-ene)bis-(1H-indole-2-carboxyl-ate).
AB  - In the title compound, C(29)H(26)N(2)O(4), the benzene ring is twisted by 73.5
      (5) and 84.9 (3) degrees  with respect to the mean planes of the two indole ring
      systems; the mean planes of the indole ring systems are oriented at a dihedral
      angle of 82.0 (5) degrees . In the crystal, mol-ecules are linked by pairs of N
      H?O hydrogen bonds into chains.

PMID- 22969646
TI  - 1-(2-Cyano-eth-yl)-1H-imidazole-4,5-dicarbonitrile.
AB  - In the title tricyano-nitrile compound, C(8)H(5)N(5), the N-substituted cyano
      ethyl group is offset to the imidazole ring [dihedral angle = 75.41 (15) degrees
      ].

PMID- 22969647
TI  - N-(2-Methyl-phen-yl)-4-nitro-benzene-sulfonamide.
AB  - In the title compound, C(13)H(12)N(2)O(4)S, the dihedral angle between the planes
      of the rings is 51.11 (10) degrees . In the crystal, mol-ecules are linked into
      inversion dimers through pairs of N-H?O(S) hydrogen bonds.

PMID- 22969648
TI  - N-(2-{[5-Bromo-2-(piperidin-1-yl)pyrimidin-4-yl]sulfan-yl}-4-meth-oxy-phen-yl)
      2,4,6-trimethyl-benzene-sulfonamide.
AB  - In the title compound, C(25)H(29)BrN(4)O(3)S(2), the benzene rings bridged by the
      sulfonamide group are tilted relative to each other by 63.9 (1) degrees  and the
      dihedral angle between the sulfur-bridged pyrimidine and benzene rings is 64.9
      (1) degrees . The mol-ecular conformation is stabilized by a weak intra-molecular
      pi-pi stacking inter-action between the pyrimidine and the 2,4,6-trimethyl
      benzene rings [centroid-centroid distance = 3.766 (2) A]. The piperidine ring
      adopts a chair conformation. In the crystal, mol-ecules are linked into inversion
      dimers by pairs of N-H?O hydrogen bonds and these dimers are further linked by C
      H?O hydrogen bonds into chains propagating along [010].

PMID- 22969649
TI  - N-(4-Chloro-phen-yl)-4-nitro-benzamide.
AB  - The title compound, C(13)H(9)ClN(2)O(3), is almost planar, showing a dihedral
      angle of 4.63 (6) degrees  between the aromatic ring planes. The nitro group also
      lies in the plane, the C-C-N-O torsion angle being 6.7 (2) degrees . There is an
      intamolecular C-H?O hydrogen bond. The crystal structure features N-H?O(nitro)
      hydrogen bonds that link the mol-ecules into zigzag chains extending along [010].

PMID- 22969650
TI  - (3'R)-3'-Benzyl-2',3'-dihydro-1H-spiro-[indole-3,1'-naphtho-[2,3-c]pyrrole]
      2,4',9'-trione.
AB  - In the title compound, C(26)H(18)N(2)O(3), the maximum deviations from planarity
      for the tetra-hydro-1H-naphtho-[2,3-c]pyrrole and indoline rings systems are
      0.091 (1) and 0.012 (2) A, respectively. These ring systems make a dihedral angle
      of 89.95 (6) degrees  with each other and they make dihedral angles of 73.42 (8)
      and 71.28 (9) degrees , respectively, with the benzene ring. In the crystal,
      inversion dimers linked by pairs of N-H?O hydrogen bonds generate R(2) (2)(8)
      loops and C-H?O inter-actions connect the dimers into corrugated sheets lying
      parallel to the bc plane.

PMID- 22969651
TI  - N-(5-Chloro-2-nitro-phen-yl)-2,2-di-methyl-propanamide.
AB  - In the crystal structure of the title compound, C(11)H(13)ClN(2)O(3), mol-ecules
      are linked through C-H?O hydrogen bonds.

PMID- 22969652
TI  - 1-Methyl-1'-(4-methyl-phen-yl)-2',3',5',6',7',7a'-hexa-hydro-1'H-dispiro
      [piperidine-3,2'-pyrrolizine-3',3''-indoline]-4,2''-dione.
AB  - The title compound, C(26)H(29)N(3)O(2), crystallizes with two mol-ecules in the
      asymmetric unit, having C-H?O inter-actions between them and resulting in a dimer
      characterized by an R(2) (2)(11) motif. These dimers are linked into an ABABAB
      chain via N-H?O, N-H?N and C-H?O built edge-fused R(1) (2)(5) and R(2) (2)(7)
      motifs. This chain is linked to its inversion-related partner via N-H?O bonds
      with an R(2) (2)(8) motif and leads to a double chain extending along the b axis
      characterized by an R(6) (6)(36) motif across the inversion centres. The methyl
      group of the phenyl ring and the oxindole of mol-ecule A and B are involved in C
      H?pi inter-actions. One C atom of the pyrrolizine ring of mol-ecule A and its
      attached H atoms show positional disorder, the major and minor components being
      in the ratio 0.706 (7):0.294 (7).

PMID- 22969653
TI  - 1-Eth-oxy-2-meth-oxy-4-[2-(4-nitro-phen-yl)ethen-yl]benzene.
AB  - In the title mol-ecule, C(17)H(17)NO(4), the dihedral angle between the two
      aromatic rings is 42.47 (7) degrees . The nitro group is twisted by 7.44 (11)
      degrees  out of the plane of the ring to which it is attached. The methoxy and
      ethoxy group O atoms deviate significantly from the phenyl ring [by 0.0108 (11)
      and 0.0449 (11) A, respectively]. The crystal structure is stabilized by C-H?pi
      inter-actions.

PMID- 22969654
TI  - N-(1,4-Dioxo-1,4-dihydro-naphthalen-2-yl)benzamide.
AB  - The title compound, C(17)H(11)NO(3), was an inter-mediate synthesized during bis
      acyl-ation of 2-amino-1,4-naphtho-quinone with benzoyl chloride. A mixture of
      block- and needle-shaped crystals were obtained after column chromatography. The
      block-shaped crystals were identified as the imide and the needles were the title
      amide. The naphtho-quinone scaffold is roughly planar (r.m.s. deviation = 0.047 A
      for the C atoms). The N-H and C=O bonds of the amide group are anti to each
      other. A dihedral angle between the naphtho-quinone ring system and the amide
      group of 3.56 (3) degrees , accompanied by a dihedral angle between the amide
      group and the phenyl group of 9.51 (3) degrees , makes the naphtho-quinone ring
      essentially coplanar with the phenyl ring [dihedral angle = 7.12 (1) degrees ].
      In the crystal, molecules are linked by a weak N-H?O hydrogen bond and by two
      weak C-H?O interactions leading to the formation of zigzag chains along [010].

PMID- 22969655
TI  - (Z)-4-[(3-Aminona-phthalen-2-yl-amino)(phen-yl)methyl-idene]-3-methyl-1-phenyl-1H
      pyrazol-5(4H)-one.
AB  - The mol-ecule of the title compound, C(27)H(22)N(4)O, assumes a non-planar
      conformation in which the pyrazolone ring forms dihedral angles of 12.73 (11),
      65.17 (6) and 49.82 (6) degrees , respectively, with the two benzene rings and
      the naphthalene ring system. In the crystal, pairs of mol-ecules are linked by
      inter-molecular N-H?N hydrogen bonds, forming dimers. The secondary amino group
      is involved in an intra-molecular N-H?O hydrogen bond.

PMID- 22969656
TI  - (E)-4-Meth-oxy-N'-[(pyridin-4-yl)methyl-idene]benzohydrazide monohydrate.
AB  - In the title compound, C(14)H(13)N(3)O(2).H(2)O, the azomethine double bond
      adopts an E conformation and the N-N=C-C torsion angle is 178.37 (19) degrees .
      The dihedral angle between the benzene and pyridine rings is 5.58 (12) degrees 
      and the C atom of the meth-oxy group is roughly coplanar with its attached ring
      [deviation = 0.157 (3) A]. In the crystal, the components are linked by O-H?O, O
      H?N, N-H?O and C-H?O hydrogen bonds, forming (001) sheets. The water O atom
      accepts one N-H?O and two C-H?O inter-actions from the adjacent organic mol
      ecule.

PMID- 22969657
TI  - (E)-1-[(3-Bromo-phen-yl)imino-meth-yl]naphthalen-2-ol.
AB  - The title compound, C(17)H(12)BrNO, exists in an enol-imine form and the mol
      ecular structure features an intra-molecular O-H?N hydrogen bond. The dihedral
      angle between the benzene ring and the naphthalene ring system is 17.27 (15)
      degrees .

PMID- 22969658
TI  - (E)-N'-(3,4-Dimeth-oxy-benzyl-idene)-4-meth-oxy-benzohydrazide.
AB  - In the title compound, C(17)H(18)N(2)O(4), the azomethine double bond adopts an E
      conformation with an N-N-C-C torsion angle of -178.3 (3) degrees . The benzene
      rings are almost coplaner, with a dihedral angle of 2.98 (14) degrees  between
      their mean planes. In the crystal, the molecules are linked by N-H?O hydrogen
      bonds, resulting in chains of mol-ecules lying parallel to the b axis. The
      structure is further consolidated by rather weak C-H?O hydrogen-bonding inter
      actions, resulting in six-membered rings about inversion centers linked into
      chains arranged parallel to the b axis.

PMID- 22969659
TI  - 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl methane-sulfonate.
AB  - The asymmetric unit of the title compound, C(7)H(11)N(3)O(5)S, contains two
      independent mol-ecules with virtually identical conformations. The imidazole
      rings of both mol-ecules are essentially planar (r.m.s. deviations = 0.0019 and
      0.0038 A), with a dihedral angle 9.25 (19) degrees  between them. The nitro
      groups are oriented at 4.5 (2) and 6.44 (13) degrees  with respect to the
      imidazole rings. In the crystal, mol-ecules are linked to form a three
      dimensional framework by C-H?O and C-H?N hydrogen bonds.

PMID- 22969660
TI  - 2-Anilino-5,7-dimethyl-pyrazolo-[1,5-a]pyrimidine-3-carbonitrile.
AB  - The title compound, C(15)H(13)N(5), crystallizes with two independent mol-ecules
      in the asymmetric unit. The mol-ecular conformations are stabilized by C-H?N
      contacts forming S(6) ring motifs. In the crystal, pairs of mol-ecules are
      connected into R(2) (2)(12) dimers by N-H?N hydrogen bonds. C-H?pi inter-actions
      and pi-pi stacking inter-actions [centroid-centroid distances = 3.6085 (8),
      3.6657 (8), 3.4745 (8) and 3.5059 (8) A] also also observed.

PMID- 22969661
TI  - 5-Amino-3-anilino-1H-pyrazole-4-carbonitrile.
AB  - In the title compound, C(10)H(9)N(5), the phenyl ring is twisted with respect to
      the pyrazole ring, forming a dihedral angle of 24.00 (6) degrees . In the
      crystal, mol-ecules are linked by N-H?N hydrogen bonds into chains running
      parallel to [010] containing alternating R(2) (2)(6) and R(2) (2)(12) rings.
      Further inter-actions are found in the crystal, viz. N-H?pi(phen-yl) inter
      actions and weak face-to-face pi-pi stacking inter-actions [centroid-centroid
      distance = 3.8890 (6) A] between the centroids of the pyrazole and phenyl rings
      are observed.

PMID- 22969662
TI  - N'-[(E)-4-Benz-yloxy-2-hy-droxy-benzyl-idene]benzohydrazide.
AB  - The title compound, C(21)H(18)N(2)O(3), exists in the E conformation with respect
      to the azomethane C=N double bond. The central benzene ring is almost coplanar
      with one of the substituent benzene rings [dihedral angle = 1.74 (5) degrees ]
      and is approximately orthogonal to the other benzene ring of the mol-ecule
      [dihedral angle = 86.61 (7) degrees ]. An intra-molecular O-H?N hydrogen bond
      occurs. The crystal packing is dominated by N-H?O hydrogen bonds, which lead to
      an infinite chain running parallel to [010].

PMID- 22969663
TI  - 2-Amino-5-methyl-pyridinium dibromo-iodate.
AB  - In the title salt, C(6)H(9)N(2) (+).Br(2)I(-), the cation is essentially planar
      (r.m.s. deviation = 0.0062 A for the non-H atoms) while the anion is almost
      linear with a Br-I-Br angle of 177.67 (2) degrees . The crystal packing shows two
      anions and two cations connected via N-H?Br and (pyridine)N-H?Br hydrogen-bonding
      inter-actions, forming centrosymmetric tetra-mers with R(4) (4)(16) ring motifs.
      Very weak offset aromatic pi-pi stacking interactions [centroid-centroid
      separation = 4.038 (4), slippage = 1.773 A] also occur.

PMID- 22969664
TI  - 3-(4-Chloro-benzo-yl)-6-(4-chloro-phen-yl)-2,4-dimethyl-benzonitrile.
AB  - In the title compound, C(22)H(15)Cl(2)NO, the terminal chloro-benzene rings are
      oriented at 44.51 (15) and 86.06 (17) degrees  with respect to the central
      polysubstituted benzene ring, and make a dihedral angle of 49.48 (17) degrees
      with each other. In the crystal, mol-ecules are linked by weak C-H?O and C-H?N
      inter-actions.

PMID- 22969665
TI  - Ethyl 6-(4-meth-oxy-phen-yl)-2-oxo-4-phenyl-cyclo-hex-3-ene-carboxyl-ate.
AB  - The asymmetric unit of the title compound, C(22)H(22)O(4), consists of two
      independent mol-ecules (A and B). The cyclo-hexene rings adopt slightly distorted
      sofa conformations in both mol-ecules. The dihedral angles between the benzene
      rings are 74.16 (13) and 71.85 (13) degrees  in mol-ecules A and B, respectively.
      In the crystal, weak C-H?O hydrogen bonds link the mol-ecules into a ribbon-like
      structure along the b axis. Weak C-H?pi inter-actions are also observed.

PMID- 22969666
TI  - 10-(Prop-1-yn-1-yl)-10H-phenothia-zine.
AB  - In the title compound, C(15)H(11)NS, the asymmetric unit comprises one half-mol
      ecule; a mirror plane passes through the S atom, the ynamine fragment, the methyl
      C atom and one methyl H atom. The phenothia-zine moiety has a butterfly
      conformation and the central six-membered ring has a boat conformation. The
      dihedral angle between the benzene rings is 149.40 (4) degrees . The crystal
      structure is stabilized by van der Waals inter-actions.

PMID- 22969667
TI  - (E)-1-[4-(Methyl-sulfan-yl)phen-yl]-2-(2,3,4-trimeth-oxy-phen-yl)ethene.
AB  - In the title compound, C(18)H(20)O(3)S, the rings are almost coplanar [inter-ring
      dihedral angle = 6.6 (2) degrees ]. In the crystal, weak C-H?O hydrogen bonds
      between the meth-oxy groups connect adjacent mol-ecules, giving chains which
      extend along [001].

PMID- 22969668
TI  - Bis(dicyclo-hexyl-aminium) 2-carb-oxy-methyl-2-hy-droxy-succinate ethanol
      monosolvate.
AB  - In the title compound, 2C(12)H(24)N(+).C(6)H(6)O(7) (2-).C(2)H(6)O, the cyclo
      hexane rings of the cations adopt chair conformations. In the anion, intra
      molecular O-H?O hydrogen bonds occur. In the crystal, the cations link with the
      anions via N-H?O hydrogen bonds. Weak C-H?O hydrogen bonds are also observed. The
      hy-droxy group of the ethanol solvent mol-ecule is disordered over two sets of
      sites with an occupancy ratio of 0.766 (5):0.234 (5).

PMID- 22969669
TI  - 7-[(7S)-7-Aza-niumyl-5-aza-spiro-[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1S,2R)-2
      fluoro-cyclo-prop-yl]-4-oxo-1,4-dihydroquinoline-3-carboxyl-ate methanol
      monosolvate.
AB  - Sitafloxacin is a newly developed fluoro-quinolone anti-bacterial drug. The
      crystal studied, C(19)H(18)ClF(2)N(3)O(3).CH(3)OH, consists of one mol-ecule of
      sitafloxacin and one methanol solvent mol-ecule. The mol-ecule of sitafloxacin is
      a zwitterion with a protonated primary amine group and a deprotonated carboxylate
      group. The cyclopropane ring and the CO(2) group make dihedral angles of 79.5 (3)
      and 35.4 (4) degrees , respectively, with the fused ring system. The supra
      molecular structure is defined by N-H?O and O-H?O hydrogen bonds.

PMID- 22969670
TI  - 2,5-Dibromo-indan-1-ol.
AB  - In the title compound, C(9)H(8)Br(2)O, the cyclo-pentene ring adopts an envelope
      conformation with the brominated C atom as the flap. In the crystal, mol-ecules
      are linked by strong O-H?O hydrogen bonds into zigzag C(4) chains along [010]. In
      addition, a C-H?pi inter-action involving the benzene ring and the H atom
      attached to the hy-droxy-lated C atom is observed.

PMID- 22969671
TI  - meso-5,10,15,20-Tetra-kis(4-hy-droxy-3-meth-oxy-phen-yl)porphyrin propionic acid
      monosolvate.
AB  - In the title compound, C(48)H(38)N(4)O(8).C(3)H(6)O(2), the porphyrin mol-ecule
      is centrosymmetric. The propionic acid solvent mol-ecule is disordered over two
      sets of sites with equal occupancy factors. The porphyrin central core is almost
      planar, with an r.m.s. deviation of the fitted atoms of 0.045 A. The substituent
      benzene rings make dihedral angles of 70.37 (4) and 66.95 (4) degrees  with
      respect to the porphyrin core plane. The crystal structure is stabilized by an
      inter-esting network of hydrogen bonds. Porphyrin mol-ecules are connected by O
      H?O hydrogen bonds creating ribbons running along the [101] direction. Weak C-H?O
      hydrogen bonds connect separate mol-ecular ribbons in the [110] direction,
      creating (-111) layers. Intra-molecular N-H?N hydrogen bonds also occur. The
      propionic acid molecules are connected by pairs of -H?O hydrogen bonds, creating
      dimers.

PMID- 22969672
TI  - 5-Chloro-2-phenyl-1,3-benzothia-zole.
AB  - In the structure of the title compound, C(13)H(8)ClNS, the dihedral angle between
      the benzothia-zole ring system and the phenyl ring is 7.11 (8) degrees . In the
      crystal, mol-ecules are arranged parallel to the c axis.

PMID- 22969673
TI  - N-(2-{[5-Bromo-2-(morpholin-4-yl)pyrimidin-4-yl]sulfan-yl}-4-meth-oxy-phen-yl)-4
      chloro-benzene-sulfonamide.
AB  - In the title compound, C(21)H(20)BrClN(4)O(4)S(2), the benzene rings bridged by
      the sulfonamide group are tilted relative to each other by a dihedral angle of
      70.2 (1) degrees  and the dihedral angle between the sulfur-bridged pyrimidine
      and benzene rings is 69.5 (1) degrees . The mol-ecular conformation is stabilized
      by a weak intra-molecular pi-pi stacking inter-action between the pyrimidine and
      the 4-chloro-benzene rings [centroid-centroid distance = 3.978 (2) A]. The
      morpholine ring adopts a chair conformation. In the crystal, mol-ecules are
      linked into inversion dimers by pairs of C-H?N hydrogen bonds and these dimers
      are further connected by N-H?O hydrogen bonds, forming a tape along the a axis.

PMID- 22969674
TI  - 4-Meth-oxy-2-{(E)-[(thio-phen-2-yl)methyl-imino]-meth-yl}phenol.
AB  - The title Schiff base, C(13)H(13)NO(2)S, adopts the phenol-imine tautomeric form
      and reveals an intra-molecular O-H?N hydrogen bond involving the hy-droxy group
      and the imino N atom, forming an S(6) ring. The mol-ecule is highly twisted with
      respect to the central imine group, which is reflected in the dihedral angle of
      67.83 (10) degrees  formed by the thienyl and phenol rings. The crystal packing
      is characterized by weak C-H?O and C-H?pi inter-actions.

PMID- 22969676
TI  - N-(2-Bromo-benz-yl)cinchoninium bromide.
AB  - The title compound {systematic name: 1-(2-bromo-benz-yl)-5-ethenyl-2-[hy
      droxy(quinolin-4-yl)meth-yl]-1-aza-bicyclo-[2.2.2]octan-1-ium bromide},
      C(26)H(28)BrN(2)O(+).Br(-), is a chiral quater-nary ammonium salt of one of the
      Cinchona alkaloids. The planes of the quinoline and of the bromo-benzyl
      substituent are inclined to one another by 9.11 (9) degrees . A weak intra
      molecular C-H?O hydrogen bond occurs. The crystal structure features strong O
      H?Br hydrogen bonds and weak C-H?Br inter-actions.

PMID- 22969675
TI  - 2-[2-(2-Chloro-phen-yl)-2-oxoeth-yl]-2,3-dihydro-1lambda(6),2-benzothia-zole
      1,1,3-trione.
AB  - The asymmetric unit of the title compound, C(15)H(10)ClNO(4)S, contains two
      independent conformers wherein the 2-chloro-phenyl group in one is rotated by
      approximately 180 degrees  compared to the other mol-ecule. This affects the S-N
      C-C(=O) and N-C-C(=O)-C torsion angles giving vlaues of -87.0 (2) and 158.7 (2)
      degrees  in one mol-ecule and -104.3 (2) and -173.4 (2) degrees  in the other.
      The benzisothia-zole ring systems in the two mol-ecules are essentially planar
      (r.m.s. deviations = 0.017 and 0.010 A) and form dihedral angles of 73.53 (7) and
      73.26 (6) degrees  with the benzene rings. In the crystal, there are weak pi-pi
      inter-actions between the benzene rings of the benzisothia-zole groups and
      symmetry-related chloro-benzene rings with centroid-centroid distances of 3.6178
      (13) and 3.6267 (15) A. In addition, pairs of weak inter-molecular C-H?O hydrogen
      bonds form inversion dimers which are connected by further C-H?O hydrogen bonds
      into a three-dimensional network.

PMID- 22969677
TI  - Redetermination of 4-cyano-pyridine N-oxide.
AB  - In the title pyridine N-oxide derivative, C(6)H(4)N(2)O, the 4-cyano substituent
      almost lies in the mean plane of the pyridine ring (r.m.s deviation of all non-H
      atoms = 0.004 A). This redetermination results in a crystal structure with
      significantly higher precision [N-O bond length is 1.2997 (15) compared with
      1.303 (5) A in the original] than the original determination, which was recorded
      using the multiple-film technique and visually estimated intensities [Hardcastle
      et al. (1974 ?). J. Cryst. Mol. Struct.4, 305-311]. The crystal structure
      features weak C-H?O and C-H?N inter-actions, which lead to the formation of
      chains that inter-sect each other parallel to (001).

PMID- 22969678
TI  - 2-Hy-droxy-ethanaminium 2-methyl-5-nitro-benzene-sulfonate.
AB  - In the crystal structure of the title salt, C(2)H(8)NO(+).C(7)H(6)NO(5)S(-), the
      cations and anions are linked together by N-H?O and O-H?O hydrogen bonds, forming
      layers parallel to (100). The plane of nitro group is skew with respect to the
      plane of benzene ring, making a dihedral angle of 17.5 (2) degrees .

PMID- 22969679
TI  - Hexa-kis-(propyl-ammonium) benzene-1,2,4,5-tetra-carboxyl-ate 2,5-dicarb-oxy
      benzene-1,4-carboxyl-ate tetra-hydrate.
AB  - The title organic salt, 6C(3)H(10)N(+).C(10)H(2)O(8) (4-).C(10)H(4)O(8) (2
      ).4H(2)O, contains seven independent entities in the asymmetric unit which
      comprises three propyl-ammonium cations, two water mol-ecules, half a 2,5-dicarb
      oxy-benzene-1,4-carboxyl-ate dianion (H(2)btc(2-)) and half a benzene-1,2,4,5
      tetra-carboxyl-ate tetra-anion (btc(4-)), the latter two anions being located
      about centres of inversion. One of the water mol-ecules is disordered over two
      positions in a 0.55 (2):0.45 (2) ratio. The combination of mol-ecular ions and
      water mol-ecules results in an extensive and complex three-dimensional network of
      hydrogen bonds, the network being made up of nine unique N-H?O inter-actions
      between the ammonium cations and the anions, as well as four unique O-H?O inter
      actions between the water mol-ecules and the anions.

PMID- 22969680
TI  - 2-Amino-6-(quinoline-2-carboxamido)-pyridinium nitrate.
AB  - In the title salt, C(15)H(13)N(4)O(+).NO(3) (-), an extensive network of N-H?N, N
      H?O and C-H?O hydrogen-bond inter-actions are observed throughout the structure.
      Further stabilization is obtained by pi-pi stacking inter-actions between
      inversion-related quinoline systems and inversion-related pyridine rings, with
      respective centroid-centroid distances of 3.5866 (6) and 3.3980 (6) A.

PMID- 22969681
TI  - 1,2-Bis{2-[2-(trimethyl-sil-yl)ethyn-yl]phen-yl}ethane-1,2-dione.
AB  - The title compound, C(24)H(26)O(2)Si(2), has C(2) crystallographic symmetry. The
      dihedral angle between the aromatic rings is 84.5 (2) degrees . The acetyl-ene
      group is slightly non-linear, with angles at the acetyl-ene C atoms of 175.7 (2)
      and 177.0 (2) degrees . In the crystal structure, only van de Waals interactions
      occur.

PMID- 22969682
TI  - N-Acetyl-5-chloro-3-nitro-l-tyrosine ethyl ester.
AB  - The title compound, C(13)H(15)ClN(2)O(6), was synthesized by hypochlorous acid
      mediated chlorination of N-acetyl-3-nitro-l-tyrosine ethyl ester. The OH group
      forms an intra-molecular O-H?O hydrogen bond to the nitro group and the N-H group
      forms an inter-molecular N-H?O hydrogen bonds to an amide O atom, linking the mol
      ecules into chains along [100]. The crystal studied was a non-merohedral twin,
      with a 0.907 (4):0.093 (4) domain ratio.

PMID- 22969683
TI  - 6-(4-Amino-phen-yl)-4-(4-eth-oxy-phen-yl)-2-meth-oxy-nicotinonitrile.
AB  - In the title mol-ecule, C(21)H(19)N(3)O(2), the central pyridine ring makes
      dihedral angles of 14.46 (9) and 34.67 (8) degrees  with the 4-amino- and 4-eth
      oxy-substituted benzene rings, respectively. The eth-oxy group is essentially
      coplanar with the attached benzene ring [C-O-C-C torsion angle = 178.70 (16)
      degrees ] as is the meth-oxy group with the pyridine ring [C-O-C-N torsion angle
      = -3.0 (3) degrees ]. In the crystal, mol-ecules are linked by N-H?N hydrogen
      bonds into chains along [201]. Weak C-H?O hydrogen bonds and C-H?pi inter-actions
      are also present.

PMID- 22969684
TI  - N-[(2S)-2-Chloro-propano-yl]glycine.
AB  - The title compound, C(5)H(8)ClNO(3), was prepared by the nucleophilic
      substitution reaction of (2S)-2-chloro-propanoyl chloride with glycine. The
      acetate group forms a dihedral angle of 84.6 (1) degrees  with the mean plane of
      the C-NH-C=O fragment. In the crystal, the molecules are linked by N-H?O and O
      H?O hydrogen bonds, generating a three-dimensional network, which consolidates
      the crystal packing.

PMID- 22969685
TI  - (E)-4-(2-Hy-droxy-3-meth-oxy-benzyl-idene-amino)-6-methyl-3-sulfanyl-idene-3,4
      dihydro-1,2,4-triazin-5(2H)-one.
AB  - In the title mol-ecule, C(12)H(12)N(4)O(3)S, there is an intra-molecular O-H?N
      hydrogen bond. The dihedral angle between the benzene and triazine rings is 65.9
      (3) degrees . In the crystal, N-H?S and O-H?N hydrogen bonds link the mol-ecules
      into chains along [010]. In addition, there are weak pi-pi stacking inter-actions
      between symmetry-related triazine rings with a centroid-centroid distance of
      3.560 (3) degrees .

PMID- 22969686
TI  - N-[4-(4-Nitro-phen-oxy)phen-yl]penta-n-amide.
AB  - The asymmetric unit of the title compound, C(17)H(18)N(2)O(4), contains two
      independent mol-ecules (A and B) differing principally in the conformations of
      the alkyl chains, anti for molecule A and gauche for molecule B. The dihedral
      angles between the aromatic rings are 82.51 (6) and 82.25 (6) degrees  in the two
      molecules. In the crystal, amide-amide inter-actions (as N-H?O=C) results in
      distinct chains of A and B mol-ecules running parallel to the a-axis direction. C
      H?O inter-actions also occur.

PMID- 22969687
TI  - 1-[Bis(4-fluoro-phen-yl)meth-yl]piperazine.
AB  - In the title mol-ecule, C(17)H(18)F(2)N(2), the dihedral angle between the
      benzene rings is 73.40 (3) degrees . The piperazine ring is close to an ideal
      chair conformation and the N-H hydrogen is in an equatorial position. In the
      crystal, molecules are linked via weak C-H?F hydrogen bonds.

PMID- 22969688
TI  - 4-Carbamoylpyridin-1-ium 2,2,2-tri-chloro-acetate-isonicotinamide (1/1).
AB  - In the crystal structure of the title 1:1 co-crystal,
      C(6)H(7)N(2)O(+).C(2)Cl(3)O(2) (-).C(6)H(6)N(2)O, the amide groups of the 4
      carbamoylpyridin-1-ium ion and the isonicotinamide mol-ecule are twisted out of
      the plane of the aromatic ring with C-C-C-N torsion angles of 21.5 (4) and -33.5
      (4) degrees , respectively. The 4-carbamoylpyridin-1-ium and isonicotinamide
      amide groups form R(2) (2)(8) hydrogen-bonded dimers via N-H?O=C inter-actions.
      The two remaining amide H atoms (i) link dimers via the cation to an
      isonicotinamide and (ii) from the isonicotinamide to a trichloro-acetate anion.
      The pyridinium H atom also forms an N-H?O hydrogen bond with the trichloro
      acetate anion. Due to the extended hydrogen bonding, including C-H?O and C-H?Cl
      interactions, all components in the structure aggregate into a three-dimensional
      supra-molecular framework.

PMID- 22969689
TI  - 3-(2-Oxo-2,3,4,5-tetra-hydro-furan-3-yl)-1-benzofuran-2-carbonitrile.
AB  - The asymmetric unit of the title compound, C(13)H(9)NO(3), consists of two
      crystallographically independent mol-ecules. In each mol-ecule, the tetra-hydro
      furan (THF) ring adopts an envelope conformation with one of the methyl-ene C
      atoms positioned at the flap. The dihedral angles between the mean plane of the
      THF and the benzofuran ring system are 70.85 (5) and 89.59 (6) degrees . In the
      crystal, mol-ecules are stacked in a column along the a-axis direction through C
      H?O hydrogen bonds, with columns further linked by C-H?N and C-H?O inter-actions.

PMID- 22969690
TI  - 3-(9H-Fluoren-9-yl)-3-(4-methyl-phen-yl)-1-phenyl-propan-1-one.
AB  - In the title compound, C(29)H(24)O, the phenyl and methyl-phenyl rings are
      approximately perpendicular to each other, making a dihedral angle of 87.67 (10)
      degrees , and are oriented at dihedral angles of 62.49 (9) and 84.77 (7) degrees
      , respectively, to the nearly planar fluorene ring system [maximum deviation =
      0.077 (2) A] In the crystal, weak C-H?pi inter-actions are observed.

PMID- 22969691
TI  - Therapeutic Hemapheresis.

PMID- 22969692
TI  - Plasma Exchange and Immunoadsorption of Patients with Thoracic Organ
      Transplantation.
AB  - Primary organ failure after transplantation (TX) remains a serious complication
      and leads to a high percentage of lethality. It is known, however, that the speed
      of rejection and tissue destruction depends on 3 main factors: antibody titer,
      the ability of the tissue to repair itself, and immunosuppressive measures.
      Especially with evidence for antibodies against human leukocyte antigen (HLA-ab),
      the immunological risk of persistent and acute episodes of rejection increases.
      The role of non-HLA-ab in rejection episodes is often underestimated and should
      be studied further. Antibody-mediated rejection (AMR) is still an unsolved
      problem in thoracic organ TX. An essential pillar of antihumoral therapy are the
      extracorporeal procedures like plasmapheresis (PP), therapeutic plasma exchange
      (TPE), and immunoadsorption (IA), because only they have the ability to remove
      preformed or de novo developed antibodies quickly and effectively. The quick
      removal of antibodies and other plasma factors through TPE or IA remains an
      effective and supportive method for treating AMR and allows the TX despite
      preformed antibodies. The pertinent literature does not disclose, however, how
      often and for how long treatment should be administered. It is known, that
      repeated treatment cycles with adequately processed plasma volume must be used to
      overcome redistribution of pathological antibodies. Based on our experience in
      heart transplant recipients with compromised graft function due to non-HLA-ab and
      HLA-ab, IA seems to be more effective.

PMID- 22969693
TI  - Leukocyte Depletion by Therapeutic Leukocytapheresis in Patients with Leukemia.
AB  - Hyperleukocytosis is a complication of various leukemias and can result in life
      threatening leukostasis. Critical white blood cell (WBC) counts are
      conventionally defined as higher than 100 * 10(9)/l in acute myeloid leukemia and
      > 300 * 10(9)/l in acute lymphatic leukemia and other leukemic disorders (e. g.
      chronic myeloid leukemia). Leukocytapheresis is a therapeutic tool to reduce
      leukocyte counts in patients with symptomatic or threatening leukostasis until
      induction chemotherapy works. In patients with temporary contraindications
      against cytotoxic drugs, e.g. during pregnancy, leukocytapheresis can be used as
      a bridging therapy until conventional chemotherapy can be started. Therapeutic
      leukocytapheresis should be performed in specialized centers by experienced, well
      trained staff. Thorough monitoring of the patients is extremely relevant. During
      a single procedure, WBC count can be reduced by 10-70%. Treatment should be
      repeated daily and can be discontinued when the symptoms of leukostasis have been
      resolved and/or leukocyte counts have fallen below the critical thresholds. There
      are no prospective studies evaluating the clinical efficacy of therapeutic
      leukocytapheresis in patients with hyperleukocytosis. It can be concluded from
      retrospective studies that leukocytapheresis might have some beneficial effect in
      early morbidity and mortality of patients with newly diagnosed AML but has no
      influence on overall long-term survival. Induction chemotherapy is the most
      important treatment in these patients and must never be postponed.

PMID- 22969694
TI  - Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for
      Patients with Inflammatory Bowel Disease.
AB  - Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory
      bowel diseases. In both cases, the medically refractory and steroid-dependent
      type presents a therapeutic challenge. To help resolve this problem, a mainly
      Japanese team developed a new therapeutic option. There are two systems, both of
      which are able to selectively remove the main mediators of the disease, namely
      the activated pro-inflammatory cytokine-producing granulocytes and
      monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte
      monocyte apheresis). One of the two systems is the Adacolumn( ((r)) )
      (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and
      a single-use column, which contains approximately 35,000 cellulose acetate beads.
      The exact mode of action is not yet sufficiently understood, but however, a
      modulation of the immune system takes place. As a result, less pro-inflammatory
      cytokines are released. Furthermore, the production of anti-inflammatory
      interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes
      boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to
      the inflamed tissue, and CD10-negative immature granulocytes appear in the
      peripheral blood. Another effect to be mentioned is the removal of the peripheral
      dendritic cells and the leachate of regulatory T cells (T-regs). The second
      system is the Cellsorba( ((r)) ) FX Filter (Asahi Medical, Tokyo, Japan). The
      range of efficiency, the indication, and the procedure are very similar to the
      Adacolumn. Solely the additional removal of lymphocytes can possibly limit the
      implementation since lymphopenia can increase the risk of autoimmune disease.
      Both systems provide a low-risk therapy with few adverse reactions. ASFA
      recommendations for GMA in inflammatory bowel disease are 2B due to the fact that
      not enough randomized double-blind studies are available to proof the efficacy of
      this treatment.

PMID- 22969695
TI  - Clinical Results of Extracorporeal Photopheresis.
AB  - Extracorporeal photopheresis (ECP) is a combination of leukapheresis and
      photodynamic therapy in which blood is treated with photoactivable drugs which
      are then activated with ultraviolet light and re-infused to the patient. It has
      been used successfully for more than 30 years in the treatment of erythrodermic
      cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host
      disease (GVHD). ECP has also shown promising results in the treatment of acute
      GVHD and other T-cell-mediated diseases, including systemic sclerosis, treatment
      and prevention of solid organ rejection, and more recently Crohn's disease. The
      use of ECP may allow a significant reduction or even discontinuation of
      corticosteroids and/or other immunosuppressants, thus leading to reduced long
      term morbidity and mortality and improved overall survival. ECP is a well
      tolerated therapy. No significant side effects have been reported during the last
      30 years. It has been shown that ECP is not associated with an increased
      incidence of infections, malignancies, or recurrence of underlying malignant
      disease, neither during short-term nor during long-term therapy.

PMID- 22969696
TI  - Extracorporeal Treatment for the Acute und Long-Term Outcome of Patients with
      Life-Threatening Acquired Hemophilia.
AB  - OBJECTIVES: In acquired hemophilia (AH), autoantibodies (inhibitors) impede blood
      coagulation factors leading to severe bleedings. Cornerstones of a successful
      treatment are the control of bleeding and an eradication of autoantibodies. The
      present study is an update of our previous documentation of the treatment of high
      titer AH patients with severe life-threatening bleeding undergoing the modified
      Bonn-Malmo-Protocol (MBMP).  METHODS: 64 AH patients were treated by a standard
      combination protocol (MBMP) consisting of antibody depletion through
      immunoadsorption, i.v. immunoglobulin, immunosuppression, and high-dose FVIII
      substitution. They underwent a long-term follow-up.  RESULTS: Primary study
      endpoints loss of detection of the activity of the inhibitor and FVIII recovery ?
      5% were reached in a median time of 3 days (95% CI: 2.6-3.4 days), the median
      time of FVIII substitution was 13 days (95% CI 10.6-15.3 days), and the median
      time of immunoadsorption was 16 days (95% CI 13-18.9 days). In 5 patients the AH
      occurred as paraneoplastic syndrome, and partial remission was achieved. Relapses
      without bleeding event occurred only in second-line MBMP. Those responded
      excellently to short time treatment. Overall patients remained in remission over
      a median follow-up time of 8 years. Conclusion: Except for paraneoplastic AH,
      MBMP-treated patients have a remarkable prognosis which is confirmed by long-term
      follow-up with a complete response rate of 93% (53/57) in the first year post
      MBMP and 100% during long-term follow-up. These outcome in life-threatening AH is
      unique and until now not achievable via other treatment schedules. In life
      threatening bleedings physicians should take into account MBMP as a first line
      treatment.

PMID- 22969697
TI  - Influence of Red Blood Cell Storage Time on Clinical Course and Cytokine Profile
      in Septic Shock Patients.
AB  - BACKGROUND: Previous investigations have suggested beneficial effects of fresh
      versus stored red blood cell transfusion in critically ill patients. The present
      study investigates the effects of red blood cell storage time on the clinical
      course and hemodynamic and laboratory parameters in patients with septic shock. 
      PATIENTS AND METHODS: 18 patients with septic shock received 2 erythrocyte units
      stored for ? 7 days (n = 8) or > 7 days (n = 10). The sequential organ failure
      assessment (SOFA) score was calculated for 7 days. Hemodynamic parameters
      (cardiac index, extravascular lung water) were determined using transpulmonary
      thermodilution. Laboratory parameters (lactate, base excess, C-reactive protein,
      procalcitonin, IL-1Beta, IL-6, TNF-alpha, sVCAM-1, sICAM-1) were monitored before
      and 1, 3, 6, 12, 24, and 48 h after transfusion. The Mann-Whitney-U test and
      Neumann test were used for group comparison and trend assessment, respectively. 
      RESULTS: We failed to observe significant differences with respect to SOFA scores
      between patients receiving fresh or stored erythrocytes. However, a significant
      trend towards an improvement in the SOFA score was found in the group receiving
      fresh erythrocytes (p < 0.01). No significant differences in hemodynamic or
      laboratory parameters were found between both groups. CONCLUSION: While the
      present findings do not provide clear-cut evidence supporting beneficial effects
      of fresh red blood cells in septic shock, they warrant larger randomized studies
      to confirm or refute such effects.

PMID- 22969698
TI  - Deformability of Red Blood Cells and Correlation with ATP Content during Storage
      as Leukocyte-Depleted Whole Blood.
AB  - BACKGROUND: Storage duration of red cells has been associated with increased
      morbidity and mortality following transfusion. This association has been
      attributed to the loss of deformability of stored red cells leading to
      deterioration of microvascular perfusion. ATP content is considered a critical
      determinant of the deformability of stored red cells.  METHODS: ATP content and
      deformability were determined after storage for up to 49 days in 40 leukocyte
      depleted whole blood units. Red cell deformability was determined using a laser
      assisted optical rotational cell analyzer (LORCA( ((r)) )) employing shear stress
      (SS) ranging from 0.3 to 30 Pa. Deformability was expressed as the elongation
      index (EI). EI was correlated with ATP content.  RESULTS: ATP content decreased
      from 3.5 to 1.7 ?mol/g hemoglobin. EI increased from 0.03 to 0.05 at an SS of 0.3
      Pa, and decreased from 0.62 to 0.59 at an SS of 30 Pa. Correlation coefficient
      (r) of ATP vs. EI at 0.3 Pa ranged from -0.17 to +0.15 during storage. At 30 Pa,
      r ranged from -0.03 to +0.45. Correlation increased with storage irrespective of
      SS, and increased with SS irrespective of storage.  CONCLUSIONS: ATP content is
      not a valid surrogate marker for red cell deformability and may not reflect in
      vivo survival of stored red cells.

PMID- 22969699
TI  - Frequency of RBC Alloantibodies in Chinese Surgical Patients.
AB  - BACKGROUND: The aim of this study was to evaluate the frequency of red blood cell
      (RBC) alloantibodies in surgical patients.  METHODS: Blood samples of 18,980
      Chinese surgical patients were collected and tested between January 2009 and
      September 2010. For patients with RBC alloantibodies, sequences of antibodies
      were identified with the DiaMed Asia antibody screening system. Data regarding
      sex, age, transfusion history, pregnancy history, and alloantibody specificity
      were collected.  RESULTS: 39 alloantibodies were identified from 18,980 samples,
      yielding a prevalence of 0.21%. The most frequently identified alloantibodies
      were Rhesus system antibodies (28/39, 71.8%), including anti-E (17/39; 1 anti-E
      accompanied by anti-Fy(b)), anti-c (5/39), anti-cE (2/39), anti-C(w) (1/39), anti
      D (1/39), and anti-e (1/39). Other antibodies included anti-M (5/39), anti-Le(a)
      (2/39), anti-Le(b) (1/39), anti-K+S (1/39), anti-JK(a) (1/39), and anti-JS(a)
      (1/39). The frequency of alloantibodies was greater in females than in males (31
      vs. 8).  CONCLUSION: The results show a higher prevalence of RBC alloantibodies
      in females than in males. Anti-E was the most common alloantibody identified in
      this Chinese surgical population and was also more frequent in females compared
      to males.

PMID- 22969700
TI  - A core circuit module for cost/benefit decision.
AB  - A simple circuit for cost-benefit decision derived from behavioral and neural
      studies of the predatory sea-slug Pleurobranchaea may closely resemble that upon
      which the more complex valuation and decision processes of the social vertebrates
      are built. The neuronal natures of the pathways in the connectionist model
      comprise classic central pattern generators, bipolar switch mechanisms, and
      neuromodulatory state regulation. Marked potential exists for exploring more
      complex neuroeconomic behavior by appending appropriate circuitry in simulo.

PMID- 22969701
TI  - Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate
      Gyrus and Subventricular Zone.
AB  - Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is
      highly expressed in adult neurogenic niches, i.e., the dentate gyrus and
      subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the
      role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1
      causes a transient increase of the proliferating dentate gyrus stem and
      progenitor cells at post-natal day 7; however, at 2 months of age the number of
      these proliferating cells, as well as of mature neurons, greatly decreases
      compared to wild-type controls. Remarkably, adult dentate gyrus stem and
      progenitor cells of Btg1-null mice exit the cell cycle after completing the S
      phase, express p53 and p21 at high levels and undergo apoptosis within 5 days. In
      the SVZ of adult (two-month-old) Btg1-null mice we observed an equivalent
      decrease, associated to apoptosis, of stem cells, neuroblasts, and neurons;
      furthermore, neurospheres derived from SVZ stem cells showed an age-dependent
      decrease of the self-renewal and expansion capacity. We conclude that ablation of
      Btg1 reduces the pool of dividing adult stem and progenitor cells in the dentate
      gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis,
      probably reflecting impairment of the control of the cell cycle transition from
      G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among
      overlapping contextual memories was affected. Btg1 appears, therefore, to be
      required for maintaining adult stem and progenitor cells quiescence and self
      renewal.

PMID- 22969702
TI  - Bromocriptine does not alter speed-accuracy tradeoff.
AB  - Being quick often comes at the expense of being accurate. This speed-accuracy
      tradeoff is a central feature of many types of decision making. It has been
      proposed that dopamine plays an important role in adjusting responses between
      fast and accurate behavior. In the current study we investigated the role of
      dopamine in perceptual decision making in humans, focusing on speed-accuracy
      tradeoff. Using a cued version of the random dot motion task, we instructed
      subjects to either make a fast or an accurate decision. We investigated decision
      making behavior in subjects who were given bromocriptine (a dopamine receptor
      agonist) or placebo. We analyzed the behavioral data using two accumulator
      models, the drift diffusion model, and the linear ballistic accumulator model. On
      a behavioral level, there were clear differences in decision threshold between
      speed and accuracy focus, but decision threshold did not differ between the drug
      and placebo sessions. Bayesian analyses support the null hypothesis that there is
      no effect of bromocriptine on decision threshold. On the neural level, we
      replicate previous findings that the striatum and pre-supplementary motor area
      are active when preparing for speed, compared with accurate decisions. We do not
      find an effect of bromocriptine on this activation. Therefore, we conclude that
      bromocriptine does not alter speed-accuracy tradeoff.

PMID- 22969703
TI  - Social learning as a way to overcome choice-induced preferences? Insights from
      humans and rhesus macaques.
AB  - Much theoretical attention is currently devoted to social learning. Yet,
      empirical studies formally comparing its effectiveness relative to individual
      learning are rare. Here, we focus on free choice, which is at the heart of
      individual reward-based learning, but absent in social learning. Choosing among
      two equally valued options is known to create a preference for the selected
      option in both humans and monkeys. We thus surmised that social learning should
      be more helpful when choice-induced preferences retard individual learning than
      when they optimize it. To test this prediction, the same task requiring to find
      which among two items concealed a reward was applied to rhesus macaques and
      humans. The initial trial was individual or social, rewarded or unrewarded.
      Learning was assessed on the second trial. Choice-induced preference strongly
      affected individual learning. Monkeys and humans performed much more poorly after
      an initial negative choice than after an initial positive choice. Comparison with
      social learning verified our prediction. For negative outcome, social learning
      surpassed or at least equaled individual learning in all subjects. For positive
      outcome, the predicted superiority of individual learning did occur in a majority
      of subjects (5/6 monkeys and 6/12 humans). A minority kept learning better
      socially though, perhaps due to a more dominant/aggressive attitude toward peers.
      Poor learning from errors due to over-valuation of personal choices is among the
      decision-making biases shared by humans and animals. The present study suggests
      that choice-immune social learning may help curbing this potentially harmful
      tendency. Learning from successes is an easier path. The present data suggest
      that whether one tends to walk it alone or with a peer's help might depend on the
      social dynamics within the actor/observer dyad.

PMID- 22969704
TI  - Addictive drugs and plasticity of glutamatergic synapses on dopaminergic neurons:
      what have we learned from genetic mouse models?
AB  - Drug-induced changes in the functional properties of neurons in the mesolimbic
      dopaminergic system are attractive candidates for the molecular underpinnings of
      addiction. A central question in this context has been how drugs of abuse affect
      synaptic plasticity on dopaminergic cells in the ventral tegmental area. We now
      know that the intake of addictive drugs is accompanied by a complex sequence of
      alterations in the properties of excitatory synapses on dopaminergic neurons,
      mainly driven by signaling and redistribution of NMDA- and AMPA-receptors. It
      has, however, been unclear how these molecular changes are related to the
      behavioral effects of addictive drugs. Recently, new genetic tools have permitted
      researchers to perform genetic intervention with plasticity-related molecules
      selectively in dopaminergic cells and to subsequently study the behaviors of
      genetically modified mice. These studies have started to reveal how plasticity
      and drug-induced behavior are connected as well as what role plasticity in
      dopaminergic cells may have in general reward learning. The findings thus far
      show that there is not a one-to-one relation between plastic events and specific
      behaviors and that the early responses to drugs of abuse are to a large extent
      independent of the types of synaptic plasticity so far targeted. In contrast,
      plasticity in dopaminergic cells indeed is an important regulator of the
      persistence of behaviors driven by drug associations, making synaptic plasticity
      in dopaminergic cells an important field of study for understanding the
      mechanisms behind relapse.

PMID- 22969705
TI  - Single-neuron diversity generated by Protocadherin-beta cluster in mouse central
      and peripheral nervous systems.
AB  - The generation of complex neural circuits depends on the correct wiring of
      neurons with diverse individual characteristics. To understand the complexity of
      the nervous system, the molecular mechanisms for specifying the identity and
      diversity of individual neurons must be elucidated. The clustered protocadherins
      (Pcdh) in mammals consist of approximately 50 Pcdh genes (Pcdh-alpha, Pcdh-beta,
      and Pcdh-gamma) that encode cadherin-family cell surface adhesion proteins.
      Individual neurons express a random combination of Pcdh-alpha and Pcdh-gamma,
      whereas the expression patterns for the Pcdh-beta genes, 22 one-exon genes in
      mouse, are not fully understood. Here we show that the Pcdh-beta genes are
      expressed in a 3'-polyadenylated form in mouse brain. In situ hybridization using
      a pan-Pcdh-beta probe against a conserved Pcdh-beta sequence showed widespread
      labeling in the brain, with prominent signals in the olfactory bulb, hippocampus,
      and cerebellum. In situ hybridization with specific probes for individual Pcdh
      beta genes showed their expression to be scattered in Purkinje cells from P10 to
      P150. The scattered expression patterns were confirmed by performing a newly
      developed single-cell 3'-RACE analysis of Purkinje cells, which clearly
      demonstrated that the Pcdh-beta genes are expressed monoallelically and
      combinatorially in individual Purkinje cells. Scattered expression patterns of
      individual Pcdh-beta genes were also observed in pyramidal neurons in the
      hippocampus and cerebral cortex, neurons in the trigeminal and dorsal root
      ganglion, GABAergic interneurons, and cholinergic neurons. Our results extend
      previous observations of diversity at the single-neuron level generated by Pcdh
      expression and suggest that the Pcdh-beta cluster genes contribute to specifying
      the identity and diversity of individual neurons.

PMID- 22969706
TI  - Direction selectivity in the larval zebrafish tectum is mediated by asymmetric
      inhibition.
AB  - The extraction of the direction of motion is an important computation performed
      by many sensory systems and in particular, the mechanism by which direction
      selective retinal ganglion cells (DS-RGCs) in the retina acquire their selective
      properties, has been studied extensively. However, whether DS-RGCs simply relay
      this information to downstream areas or whether additional and potentially de
      novo processing occurs in these recipient structures is a matter of great
      interest. Neurons in the larval zebrafish tectum, the largest retino-recipent
      area in this animal, show direction-selective (DS) responses to moving visual
      stimuli but how these properties are acquired is still unknown. In order to study
      this, we first used two-photon calcium imaging to classify the population
      responses of tectal cells to bars moving at different speeds and in different
      directions. Subsequently, we performed in vivo whole cell electrophysiology on
      these DS tectal neurons and we found that their inhibitory inputs were strongly
      biased toward the null direction of motion, whereas the excitatory inputs showed
      little selectivity. In addition, we found that excitatory currents evoked by a
      stimulus moving in the preferred direction occurred before the inhibitory
      currents whereas a stimulus moving in the null direction evoked currents in the
      reverse temporal order. The membrane potential modulations resulting from these
      currents were enhanced by the spike generation mechanism to generate amplified
      direction selectivity in the spike output. Thus, our results implicate a local
      inhibitory circuit in generating direction selectivity in tectal neurons.

PMID- 22969707
TI  - Low-threshold potassium currents stabilize IID-sensitivity in the inferior
      colliculus.
AB  - The inferior colliculus (IC) is a midbrain nucleus that exhibits sensitivity to
      differences in interaural time and intensity (ITDs and IIDs) and integrates
      information from the auditory brainstem to provide an unambiguous representation
      of sound location across the azimuth. Further upstream, in the lateral superior
      olive (LSO), absence of low-threshold potassium currents in Kcna1(-/-) mice
      interfered with response onset timing and restricted IID-sensitivity to the
      hemifield of the excitatory ear. Assuming the IID-sensitivity in the IC to be at
      least partly inherited from LSO neurons, the IC IID-encoding was compared between
      wild-type (Kcna1(+/+)) and Kcna1(-/-) mice. We asked whether the effect observed
      in the Kcna1(-/-) LSO is (1) simply propagated into the IC, (2) is enhanced and
      amplified or, (3) alternatively, is compensated and so no longer detectable. Our
      results show that general IC response properties as well as the distribution of
      IID-functions were comparable in Kcna1(-/-) and Kcna1(+/+) mice. In agreement
      with the literature IC neurons exhibited a higher level-invariance of IID
      sensitivity compared to LSO neurons. However, manipulating the timing between the
      inputs of the two ears caused significantly larger shifts of IID-sensitivity in
      Kcna1(-/-) mice, whereas in the wild-type IC the IID functions were stable and
      less sensitive to changes of the temporal relationship between the binaural
      inputs. We conclude that the IC not only inherits IID-sensitivity from the LSO,
      but that the convergence with other, non-olivary inputs in the wild-type IC acts
      to quality-control, consolidate, and stabilize IID representation; this necessary
      integration of inputs is impaired in the absence of the low-threshold potassium
      currents mediated by Kv1.1.

PMID- 22969708
TI  - A further analysis of olfactory cortex development.
AB  - The olfactory cortex (OC) is a complex yet evolutionarily well-conserved brain
      region, made up of heterogeneous cell populations that originate in different
      areas of the developing telencephalon. Indeed, these cells are among the first
      cortical neurons to differentiate. To date, the development of the OC has been
      analyzed using birthdating techniques along with molecular markers and in vivo or
      in vitro tracking methods. In the present study, we sought to determine the
      origin and adult fate of these cell populations using ultrasound-guided in utero
      injections and electroporation of different genomic plasmids into the lateral
      walls of the ventricles. Our results provide direct evidence that in the mouse
      OC, cell fate is determined by the moment and place of origin of each specific
      cell populations. Moreover, by combining these approaches with the analysis of
      specific cell markers, we show that the presence of pallial and subpallial
      markers in these areas is independent of cell origin.

PMID- 22969709
TI  - Automated diagnoses of attention deficit hyperactive disorder using magnetic
      resonance imaging.
AB  - Successful automated diagnoses of attention deficit hyperactive disorder (ADHD)
      using imaging and functional biomarkers would have fundamental consequences on
      the public health impact of the disease. In this work, we show results on the
      predictability of ADHD using imaging biomarkers and discuss the scientific and
      diagnostic impacts of the research. We created a prediction model using the
      landmark ADHD 200 data set focusing on resting state functional connectivity (rs
      fc) and structural brain imaging. We predicted ADHD status and subtype, obtained
      by behavioral examination, using imaging data, intelligence quotients and other
      covariates. The novel contributions of this manuscript include a thorough
      exploration of prediction and image feature extraction methodology on this form
      of data, including the use of singular value decompositions (SVDs), CUR
      decompositions, random forest, gradient boosting, bagging, voxel-based
      morphometry, and support vector machines as well as important insights into the
      value, and potentially lack thereof, of imaging biomarkers of disease. The key
      results include the CUR-based decomposition of the rs-fc-fMRI along with gradient
      boosting and the prediction algorithm based on a motor network parcellation and
      random forest algorithm. We conjecture that the CUR decomposition is largely
      diagnosing common population directions of head motion. Of note, a byproduct of
      this research is a potential automated method for detecting subtle in-scanner
      motion. The final prediction algorithm, a weighted combination of several
      algorithms, had an external test set specificity of 94% with sensitivity of 21%.
      The most promising imaging biomarker was a correlation graph from a motor network
      parcellation. In summary, we have undertaken a large-scale statistical
      exploratory prediction exercise on the unique ADHD 200 data set. The exercise
      produced several potential leads for future scientific exploration of the
      neurological basis of ADHD.

PMID- 22969710
TI  - Classification of ADHD children through multimodal magnetic resonance imaging.
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most common
      diseases in school-age children. To date, the diagnosis of ADHD is mainly
      subjective and studies of objective diagnostic method are of great importance.
      Although many efforts have been made recently to investigate the use of
      structural and functional brain images for the diagnosis purpose, few of them are
      related to ADHD. In this paper, we introduce an automatic classification
      framework based on brain imaging features of ADHD patients and present in detail
      the feature extraction, feature selection, and classifier training methods. The
      effects of using different features are compared against each other. In addition,
      we integrate multimodal image features using multi-kernel learning (MKL). The
      performance of our framework has been validated in the ADHD-200 Global
      Competition, which is a world-wide classification contest on the ADHD-200
      datasets. In this competition, our classification framework using features of
      resting-state functional connectivity (FC) was ranked the 6th out of 21
      participants under the competition scoring policy and performed the best in terms
      of sensitivity and J-statistic.

PMID- 22969711
TI  - High reward makes items easier to remember, but harder to bind to a new temporal
      context.
AB  - Learning through reward is central to adaptive behavior. Indeed, items are
      remembered better if they are experienced while participants expect a reward, and
      people can deliberately prioritize memory for high- over low-valued items. Do
      memory advantages for high-valued items only emerge after deliberate
      prioritization in encoding? Or, do reward-based memory enhancements also apply to
      unrewarded memory tests and to implicit memory? First, we tested for a high-value
      memory advantage in unrewarded implicit- and explicit-tests (Experiment 1).
      Participants first learned high or low-reward values of 36 words, followed by
      unrewarded lexical decision and free-recall tests. High-value words were judged
      faster in lexical decision, and more often recalled in free recall. These two
      memory advantages for high-value words were negatively correlated suggesting at
      least two mechanisms by which reward value can influence later item-memorability.
      The ease with which the values were originally acquired explained the negative
      correlation: people who learned values earlier showed reward effects in implicit
      memory whereas people who learned values later showed reward effects in explicit
      memory. We then asked whether a high-value advantage would persist if trained
      items were linked to a new context (Experiments 2a and 2b). Following the same
      value training as in Experiment 1, participants learned lists composed of
      previously trained words mixed with new words, each followed by free recall.
      Thus, participants had to retrieve words only from the most recent list,
      irrespective of their values. High- and low-value words were recalled equally,
      but low-value words were recalled earlier than high-value words and high-value
      words were more often intruded (proactive interference). Thus, the high-value
      advantage holds for implicit- and explicit-memory, but comes with a side effect:
      High-value items are more difficult to relearn in a new context. Similar to
      emotional arousal, reward value can both enhance and impair memory.

PMID- 22969713
TI  - Human striatum is differentially activated by delayed, omitted, and immediate
      registering feedback.
AB  - The temporal contingency of feedback during conversations is an essential
      requirement of a successful dialog. In the current study, we investigated the
      effects of delayed and omitted registering feedback on fMRI activation and
      compared both unexpected conditions to immediate feedback. In the majority of
      trials of an auditory task, participants received an immediate visual feedback
      which merely indicated that a button press was registered but not whether the
      response was correct or not. In a minority of trials, and thus unexpectedly, the
      feedback was omitted, or delayed by 500 ms. The results reveal a response
      hierarchy of activation strength in the dorsal striatum and the substantia nigra:
      the response to the delayed feedback was larger compared to immediate feedback
      and immediate feedback showed a larger activation compared to the omission of
      feedback. This suggests that brain regions typically involved in reward
      processing are also activated by non-rewarding, registering feedback.
      Furthermore, the comparison with immediate feedback revealed that both omitted
      and delayed feedback significantly modulated activity in a network of brain
      regions that reflects attentional demand and adjustments in cognitive and action
      control, i.e., the posterior medial frontal cortex (pMFC), right dorsolateral
      prefrontal cortex (dlPFC), bilateral anterior insula (aI), inferior frontal gyrus
      (Gfi), and inferior parietal lobe (Lpi). This finding emphasizes the importance
      of immediate feedback in human-computer interaction, as the effects of delayed
      feedback on brain activity in the described network seem to be similar to that of
      omitted feedback.

PMID- 22969712
TI  - Neural systems supporting cognitive-affective interactions in adolescence: the
      role of puberty and implications for affective disorders.
AB  - Evidence from longitudinal studies suggests that adolescence may represent a
      period of vulnerability that, in the context of adverse events, could contribute
      to developmental trajectories toward behavioral and emotional health problems,
      including affective disorders. Adolescence is also a sensitive period for the
      development of neural systems supporting cognitive-affective processes, which
      have been implicated in the pathophysiology of affective disorders such as
      anxiety and mood disorders. In particular, the onset of puberty brings about a
      cascade of physical, hormonal, psychological, and social changes that contribute
      in complex ways to the development of these systems. This article provides a
      brief overview of neuroimaging research pertaining to the development of
      cognitive-affective processes in adolescence. It also includes a brief review of
      evidence from animal and human neuroimaging studies suggesting that sex steroids
      influence the connectivity between prefrontal cortical and subcortical limbic
      regions in ways that contribute to increased reactivity to emotionally salient
      stimuli. We integrate these findings in the context of a developmental affective
      neuroscience framework suggesting that the impact of rising levels of sex
      steroids during puberty on fronto-limbic connectivity may be even greater in the
      context of protracted development of prefrontal cortical regions in adolescence.
      We conclude by discussing the implications of these findings for future research
      aimed at identifying neurodevelopmental markers of risk for future onset of
      affective disorders.

PMID- 22969715
TI  - The cinema-cognition dialogue: a match made in brain.
AB  - That human evolution amalgamates biological and cultural change is taken as a
      given, and that the interaction of brain, body, and culture is more reciprocal
      then initially thought becomes apparent as the science of evolution evolves
      (Jablonka and Lamb, 2005). The contribution of science and technology to this
      evolutionary process is probably the first to come to mind. The biology of Homo
      sapiens permits and promotes the development of technologies and artefacts that
      enable us to sense and reach physical niches previously inaccessible. This
      extends our biological capabilities, but is also expected to create selective
      pressures on these capabilities. The jury is yet out on the pace at which
      critical biological changes take place in evolution. There is no question,
      however, that the kinetics of technological and cultural change is much faster,
      rendering the latter particularly important in the biography of the individual
      and the species alike. The capacity of art to enrich human capabilities is
      recurrently discussed by philosophers and critics (e.g., Arsitotle/Poetics,
      Richards, 1925; Smith and Parks, 1951; Gibbs, 1994). Yet less attention is
      commonly allotted to the role of the arts in the aforementioned ongoing
      evolutional tango. My position is that the art of cinema is particularly suited
      to explore the intriguing dialogue between art and the brain. Further, in the
      following set of brief notes, intended mainly to trigger further thinking on the
      subject, I posit that cinema provides an unparalleled and highly rewarding
      experimentation space for the mind of the individual consumer of that art. In
      parallel, it also provides a useful and promising device for investigating brain
      and cognition.

PMID- 22969714
TI  - Error awareness and salience processing in the oddball task: shared neural
      mechanisms.
AB  - A body of work suggests similarities in the way we become aware of an error and
      process motivationally salient events. Yet, evidence for a shared neural
      mechanism has not been provided. A within subject investigation of the brain
      regions involved in error awareness and salience processing has not been
      reported. While the neural response to motivationally salient events is
      classically studied during target detection after longer target-to-target
      intervals in an oddball task and engages a widespread insula-thalamo-cortical
      brain network, error awareness has recently been linked to, most prominently,
      anterior insula cortex. Here we explore whether the anterior insula activation
      for error awareness is related to salience processing, by testing for activation
      overlap in subjects undergoing two different task settings. Using a within
      subjects design, we show activation overlap in six major brain areas during aware
      errors in an antisaccade task and during target detection after longer target-to
      target intervals in an oddball task: anterior insula, anterior cingulate,
      supplementary motor area, thalamus, brainstem, and parietal lobe. Within subject
      analyses shows that the insula is engaged in both error awareness and the
      processing of salience, and that the anterior insula is more involved in both
      processes than the posterior insula. The results of a fine-grained spatial
      pattern overlap analysis between active clusters in the same subjects indicates
      that even if the anterior insula is activated for both error awareness and
      salience processing, the two types of processes might tend to activate non
      identical neural ensembles on a finer-grained spatial level. Together, these
      outcomes suggest a similar functional phenomenon in the two different task
      settings. Error awareness and salience processing share a functional anatomy,
      with a tendency toward subregional dorsal and ventral specialization within the
      anterior insula.

PMID- 22969716
TI  - Differential vulnerability of substantia nigra and corpus striatum to oxidative
      insult induced by reduced dietary levels of essential fatty acids.
AB  - Oxidative stress (OS) has been implicated in the etiology of certain
      neurodegenerative disorders. Some of these disorders have been associated with
      unbalanced levels of essential fatty acids (EFA). The response of certain brain
      regions to OS, however, is not uniform and a selective vulnerability or
      resilience can occur. In our previous study on rat brains, we observed that a two
      generation EFA dietary restriction reduced the number and size of dopaminergic
      neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether
      OS contributes to this effect, we assessed the status of lipid peroxidation (LP)
      and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to
      this dietary treatment for one (F1) or two (F2) generations. Wistar rats were
      raised from conception on control or experimental diets containing adequate or
      reduced levels of linoleic and alpha-linolenic fatty acids, respectively. LP was
      measured using the thiobarbituric acid reaction method (TBARS) and the total
      superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were
      assessed. The experimental diet significantly reduced the docosahexaenoic acid
      (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1
      adult animals of the experimental group there was no LP in both SN and CS.
      Consistently, there was a significant increase in the t-SOD activity (p < 0.01)
      in both regions. In EF2 young animals, degeneration in dopaminergic and non
      dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in
      the CAT activity (p < 0.001) were detected in the SN, while no inter-group
      difference was found for these parameters in the CS. Conversely, a significant
      increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental
      group compared to the control. The results show that unbalanced EFA dietary
      levels reduce the redox balance in the SN and reveal mechanisms of resilience in
      the CS under this stressful condition.

PMID- 22969717
TI  - Neural Oscillations in Speech: Don't be Enslaved by the Envelope.

PMID- 22969719
TI  - Post-publication peer review: opening up scientific conversation.

PMID- 22969720
TI  - Fusimotor control of spindle sensitivity regulates central and peripheral coding
      of joint angles.
AB  - Proprioceptive afferents from muscle spindles encode information about peripheral
      joint movements for the central nervous system (CNS). The sensitivity of muscle
      spindle is nonlinearly dependent on the activation of gamma (gamma) motoneurons
      in the spinal cord that receives inputs from the motor cortex. How fusimotor
      control of spindle sensitivity affects proprioceptive coding of joint position is
      not clear. Furthermore, what information is carried in the fusimotor signal from
      the motor cortex to the muscle spindle is largely unknown. In this study, we
      addressed the issue of communication between the central and peripheral
      sensorimotor systems using a computational approach based on the virtual arm (VA)
      model. In simulation experiments within the operational range of joint movements,
      the gamma static commands (gamma(s)) to the spindles of both mono-articular and
      bi-articular muscles were hypothesized (1) to remain constant, (2) to be
      modulated with joint angles linearly, and (3) to be modulated with joint angles
      nonlinearly. Simulation results revealed a nonlinear landscape of Ia afferent
      with respect to both gamma(s) activation and joint angle. Among the three
      hypotheses, the constant and linear strategies did not yield Ia responses that
      matched the experimental data, and therefore, were rejected as plausible
      strategies of spindle sensitivity control. However, if gamma(s) commands were
      quadratically modulated with joint angles, a robust linear relation between Ia
      afferents and joint angles could be obtained in both mono-articular and bi
      articular muscles. With the quadratic strategy of spindle sensitivity control,
      gamma(s) commands may serve as the CNS outputs that inform the periphery of
      central coding of joint angles. The results suggest that the information of joint
      angles may be communicated between the CNS and muscles via the descending
      gamma(s) efferent and Ia afferent signals.

PMID- 22969721
TI  - Life history theory and social psychology.

PMID- 22969722
TI  - Telemetric assessment of referred vaginal hyperalgesia and the effect of
      indomethacin in a rat model of endometriosis.
AB  - Symptoms of endometriosis (ENDO), among others, include pelvic/abdominal and
      muscle pain. Non-steroidal anti-inflammatory agents are first-line treatment for
      this pain. Similar to women, rats with surgically induced ENDO, but not its
      surgical control, exhibit vaginal hyperalgesia, which in rats is evidenced by a
      decreased threshold for the visceromotor response (VMR) induced by vaginal
      distention. Here we assess the VMR in rats with implanted probes that
      telemetrically transmit EMG activity from the abdominal muscle. The feasibility
      and sensitivity of this technique for monitoring the VMR threshold across the
      estrous cycle and the influence of Indomethacin on ENDO-induced vaginal
      hyperalgesia were evaluated. VMR thresholds in response to vaginal distention
      with an infusion pump were measured in different estrous stages. Indomethacin (5
      or 10 mg/kg i.p. or s.c.) was injected in proestrus rats and 40-60 min later the
      VMR threshold was measured. The VMR threshold varied across the estrous cycle
      only in ENDO rats, being lowest in proestrus. Indomethacin increased this
      threshold in proestrus ENDO rats. These results show that telemetric assessment
      of the VMR is a sensitive tool, suitable for long-term studies in conscious rats.
      The results with this technique also suggest that ENDO-associated vaginal
      hyperalgesia involves COX activity, the feature that also underlies inflammatory
      pains.

PMID- 22969718
TI  - Neural synchrony within the motor system: what have we learned so far?
AB  - Synchronization of neural activity is considered essential for information
      processing in the nervous system. Both local and inter-regional synchronization
      are omnipresent in different frequency regimes and relate to a variety of
      behavioral and cognitive functions. Over the years, many studies have sought to
      elucidate the question how alpha/mu, beta, and gamma synchronization contribute
      to motor control. Here, we review these studies with the purpose to delineate
      what they have added to our understanding of the neural control of movement. We
      highlight important findings regarding oscillations in primary motor cortex,
      synchronization between cortex and spinal cord, synchronization between cortical
      regions, as well as abnormal synchronization patterns in a selection of motor
      dysfunctions. The interpretation of synchronization patterns benefits from
      combining results of invasive and non-invasive recordings, different data
      analysis tools, and modeling work. Importantly, although synchronization is
      deemed to play a vital role, it is not the only mechanism for neural
      communication. Spike timing and rate coding act together during motor control and
      should therefore both be accounted for when interpreting movement-related
      activity.

PMID- 22969723
TI  - mGluR-Dependent Synaptic Plasticity in Drug-Seeking.
AB  - A primary feature of drug addiction is the compulsive use despite negative
      consequences. A general consensus is emerging on the capacity of addictive
      substances to co-opt synaptic transmission and synaptic plasticity in brain
      circuits which are involved in reinforcement and reward processing. A current
      hypothesis is that drug-driven neuroadaptations during learning and memory
      processes divert the functions of these brain circuits, eventually leading to
      addictive behaviors. Metabotropic glutamate receptors (mGluRs) not only lead to
      long-term modulation of synaptic transmission but they have been implicated in
      drug-evoked synaptic plasticity and drug-seeking behaviors in two important ways.
      mGluR-dependent modulation of synaptic transmission is impaired by drug
      experience but interestingly their activation has been indicated as a strategy to
      restore baseline transmission after drug-evoked synaptic plasticity. Here we
      focus on the cellular mechanisms underlying mGluR-dependent long-term changes of
      excitatory synapses, and review results implicating these receptors in drug
      evoked synaptic plasticity.

PMID- 22969724
TI  - Vascularization of Air Sinuses and Fat Bodies in the Head of the Bottlenose
      Dolphin (Tursiops truncatus): Morphological Implications on Physiology.
AB  - Cetaceans have long been considered capable of limiting diving-induced nitrogen
      absorption and subsequent decompression sickness through a series of behavioral,
      anatomical, and physiological adaptations. Recent studies however suggest that in
      some situations these adaptive mechanisms might be overcome, resulting in lethal
      and sublethal injuries. Perhaps most relevant to this discussion is the finding
      of intravascular gas and fat emboli in mass-stranded beaked whales. Although the
      source of the gas emboli has as yet to been ascertained, preliminary findings
      suggest nitrogen is the primary component. Since nitrogen gas embolus formation
      in divers is linked to nitrogen saturation, it seems premature to dismiss similar
      pathogenic mechanisms in breath-hold diving cetaceans. Due to the various
      anatomical adaptations in cetacean lungs, the pulmonary system is thought of as
      an unlikely site of significant nitrogen absorption. The accessory sinus system
      on the ventral head of odontocete cetaceans contains a sizeable volume of air
      that is exposed to the changing hydrostatic pressures during a dive, and is
      intimately associated with vasculature potentially capable of absorbing nitrogen
      through its walls. The source of the fat emboli has also remained elusive. Most
      mammalian fat deposits are considered poorly vascularized and therefore unlikely
      sites of intravascular introduction of lipid, although cetacean blubber may not
      be as poorly vascularized as previously thought. We present new data on the
      vasculature of air sinuses and acoustic fat bodies in the head of bottlenose
      dolphins and compare it to published accounts. We show that the mandibular fat
      bodies and accessory sinus system are associated with extensive venous plexuses
      and suggest potential physiological and pathological implications.

PMID- 22969725
TI  - The role of inflammatory cells in fostering pancreatic cancer cell growth and
      invasion.
AB  - The pancreatic ductal adenocarcinoma (PDAC) microenvironment accommodates a
      variety of cell types and a plethora of complex interactions between tumor cells,
      host cells and extracellular matrix (ECM) components. Here we review the role of
      inflammatory cells, in particular mast cells, myeloid-derived suppressor cells,
      macrophages, T regulatory cells, T helper cells and neutrophils. The picture that
      emerges is that of a tumor microenvironment, in which the immune response is
      actively suppressed, and inflammatory cells contribute in a variety of ways to
      tumor progression.

PMID- 22969727
TI  - Heart rate variability changes at 2400 m altitude predicts acute mountain
      sickness on further ascent at 3000-4300 m altitudes.
AB  - OBJECTIVE: If the body fails to acclimatize at high altitude, acute mountain
      sickness (AMS) may result. For the early detection of AMS, changes in cardiac
      autonomic function measured by heart rate variability (HRV) may be more sensitive
      than clinical symptoms alone. The purpose of this study was to ascertain if the
      changes in HRV during ascent are related to AMS. METHODS: We followed Lake Louise
      Score (LLS), arterial oxygen saturation at rest (R-SpO(2)) and exercise (Ex
      SpO(2)) and HRV parameters daily in 36 different healthy climbers ascending from
      2400 m to 6300 m altitudes during five different expeditions. RESULTS: After an
      ascent to 2400 m, root mean square successive differences, high-frequency power
      (HF(2 min)) of HRV were 17-51% and Ex-SpO(2) was 3% lower in those climbers who
      suffered from AMS at 3000 to 4300 m than in those only developing AMS later
      (>=5000 m) or not at all (all p < 0.01). At the altitude of 2400 m RMSSD(2 min)
      <= 30 ms and Ex-SpO(2) <= 91% both had 92% sensitivity for AMS if ascent
      continued without extra acclimatization days. CONCLUSIONS: Changes in supine HRV
      parameters at 2400 m were related to AMS at 3000-4300 m Thus, analyses of HRV
      could offer potential markers for identifying the climbers at risk for AMS.

PMID- 22969728
TI  - A Systems Biology Approach to Deciphering the Etiology of Steatosis Employing
      Patient-Derived Dermal Fibroblasts and iPS Cells.
AB  - Non-alcoholic fatty liver disease comprises a broad spectrum of disease states
      ranging from simple steatosis to non-alcoholic steatohepatitis. As a result of
      increases in the prevalences of obesity, insulin resistance, and hyperlipidemia,
      the number of people with hepatic steatosis continues to increase. Differences in
      susceptibility to steatohepatitis and its progression to cirrhosis have been
      attributed to a complex interplay of genetic and external factors all addressing
      the intracellular network. Increase in sugar or refined carbohydrate consumption
      results in an increase of insulin and insulin resistance that can lead to the
      accumulation of fat in the liver. Here we demonstrate how a multidisciplinary
      approach encompassing cellular reprogramming, transcriptomics, proteomics,
      metabolomics, modeling, network reconstruction, and data management can be
      employed to unveil the mechanisms underlying the progression of steatosis.
      Proteomics revealed reduced AKT/mTOR signaling in fibroblasts derived from
      steatosis patients and further establishes that the insulin-resistant phenotype
      is present not only in insulin-metabolizing central organs, e.g., the liver, but
      is also manifested in skin fibroblasts. Transcriptome data enabled the generation
      of a regulatory network based on the transcription factor SREBF1, linked to a
      metabolic network of glycerolipid, and fatty acid biosynthesis including the
      downstream transcriptional targets of SREBF1 which include LIPIN1 (LPIN) and low
      density lipoprotein receptor. Glutathione metabolism was among the pathways
      enriched in steatosis patients in comparison to healthy controls. By using a
      model of the glutathione pathway we predict a significant increase in the flux
      through glutathione synthesis as both gamma-glutamylcysteine synthetase and
      glutathione synthetase have an increased flux. We anticipate that a larger cohort
      of patients and matched controls will confirm our preliminary findings presented
      here.

PMID- 22969726
TI  - Extrasynaptic exocytosis and its mechanisms: a source of molecules mediating
      volume transmission in the nervous system.
AB  - We review the evidence of exocytosis from extrasynaptic sites in the soma,
      dendrites, and axonal varicosities of central and peripheral neurons of
      vertebrates and invertebrates, with emphasis on somatic exocytosis, and how it
      contributes to signaling in the nervous system. The finding of secretory vesicles
      in extrasynaptic sites of neurons, the presence of signaling molecules (namely
      transmitters or peptides) in the extracellular space outside synaptic clefts, and
      the mismatch between exocytosis sites and the location of receptors for these
      molecules in neurons and glial cells, have long suggested that in addition to
      synaptic communication, transmitters are released, and act extrasynaptically. The
      catalog of these molecules includes low molecular weight transmitters such as
      monoamines, acetylcholine, glutamate, gama-aminobutiric acid (GABA), adenosine-5
      triphosphate (ATP), and a list of peptides including substance P, brain-derived
      neurotrophic factor (BDNF), and oxytocin. By comparing the mechanisms of
      extrasynaptic exocytosis of different signaling molecules by various neuron types
      we show that it is a widespread mechanism for communication in the nervous system
      that uses certain common mechanisms, which are different from those of synaptic
      exocytosis but similar to those of exocytosis from excitable endocrine cells.
      Somatic exocytosis has been measured directly in different neuron types. It
      starts after high-frequency electrical activity or long experimental
      depolarizations and may continue for several minutes after the end of
      stimulation. Activation of L-type calcium channels, calcium release from
      intracellular stores and vesicle transport towards the plasma membrane couple
      excitation and exocytosis from small clear or large dense core vesicles in
      release sites lacking postsynaptic counterparts. The presence of synaptic and
      extrasynaptic exocytosis endows individual neurons with a wide variety of time-
      and space-dependent communication possibilities. Extrasynaptic exocytosis may be
      the major source of signaling molecules producing volume transmission and by
      doing so may be part of a long duration signaling mode in the nervous system.

PMID- 22969730
TI  - Intracellular calcium signals display an avalanche-like behavior over multiple
      lengthscales.
AB  - Many natural phenomena display "self-organized criticality" (SOC), (Bak et al.,
      1987). This refers to spatially extended systems for which patterns of activity
      characterized by different lengthscales can occur with a probability density that
      follows a power law with pattern size. Differently from power laws at phase
      transitions, systems displaying SOC do not need the tuning of an external
      parameter. Here we analyze intracellular calcium (Ca(2+)) signals, a key
      component of the signaling toolkit of almost any cell type. Ca(2+) signals can
      either be spatially restricted (local) or propagate throughout the cell (global).
      Different models have suggested that the transition from local to global signals
      is similar to that of directed percolation. Directed percolation has been
      associated, in turn, to the appearance of SOC. In this paper we discuss these
      issues within the framework of simple models of Ca(2+) signal propagation. We
      also analyze the size distribution of local signals ("puffs") observed in
      immature Xenopus Laevis oocytes. The puff amplitude distribution obtained from
      observed local signals is not Gaussian with a noticeable fraction of large size
      events. The experimental distribution of puff areas in the spatio-temporal record
      of the image has a long tail that is approximately log-normal. The distribution
      can also be fitted with a power law relationship albeit with a smaller goodness
      of fit. The power law behavior is encountered within a simple model that includes
      some coupling among individual signals for a wide range of parameter values. An
      analysis of the model shows that a global elevation of the Ca(2+) concentration
      plays a major role in determining whether the puff size distribution is long
      tailed or not. This suggests that Ca(2+)-clearing from the cytosol is key to
      determine whether IP(3)-mediated Ca(2+) signals can display a SOC-like behavior
      or not.

PMID- 22969729
TI  - Glucagon secretion and signaling in the development of diabetes.
AB  - Normal release of glucagon from pancreatic islet alpha-cells promotes glucose
      mobilization, which counteracts the hypoglycemic actions of insulin, thereby
      ensuring glucose homeostasis. In treatment of diabetes aimed at rigorously
      reducing hyperglycemia to avoid chronic complications, the resulting hypoglycemia
      triggering glucagon release from alpha-cells is frequently impaired, with ensuing
      hypoglycemic complications. This review integrates the physiology of glucagon
      secretion regulating glucose homeostasis in vivo to single alpha-cell signaling,
      and how both become perturbed in diabetes. alpha-cells within the social milieu
      of the islet micro-organ are regulated not only by intrinsic signaling events but
      also by paracrine regulation, particularly by adjacent insulin-secreting beta
      cells and somatostatin-secreting delta-cells. We discuss the intrinsic alpha-cell
      signaling events, including glucose sensing and ion channel regulation leading to
      glucagon secretion. We then discuss the complex crosstalk between the islet cells
      and the breakdown of this crosstalk in diabetes contributing to the dysregulated
      glucagon secretion. Whereas, there are many secretory products released by beta-
      and delta-cells that become deficient or excess in diabetes, we discuss the major
      ones, including the better known insulin and lesser known somatostatin, which act
      as putative paracrine on/off switches that very finely regulate alpha-cell
      secretory responses in health and diabetes. Of note in several type 1 diabetes
      (T1D) rodent models, blockade of excess somatostatin actions on alpha-cell could
      normalize glucagon secretion sufficient to attain normoglycemia in response to
      hypoglycemic assaults. There has been slow progress in fully elucidating the
      pathophysiology of the alpha-cell in diabetes because of the small number of
      alpha-cells within an islet and the islet mass becomes severely reduced and
      inflamed in diabetes. These limitations are just now being surmounted by new
      approaches.

PMID- 22969731
TI  - Relationship of sleep quality and health-related quality of life in adolescents
      according to self- and proxy ratings: a questionnaire survey.
AB  - INTRODUCTION: Sleep disturbances are common in adolescents and adversely affect
      performance, social contact, and susceptibility to stress. We investigated the
      hypothesis of a relationship between sleep and health-related quality of life
      (HRQoL), and applied self- and proxy ratings. MATERIALS AND METHODS: The sample
      comprised 92 adolescents aged 11-17 years. All participants and their parents
      completed a HRQoL measure and the Sleep Disturbance Scale for Children (SDSC).
      Children with SDSC T-scores above the normal range (above 60) were classified as
      poor sleepers. RESULTS: According to self- and proxy ratings, good sleepers
      reported significantly higher HRQoL than poor sleepers. Sleep disturbances were
      significantly higher and HRQoL significantly lower in self- as compared to
      parental ratings. Parent-child agreement was higher for subscales measuring
      observable aspects. Girls experienced significantly stronger sleep disturbances
      and lower self-rated HRQoL than boys. DISCUSSION: Our findings support the
      positive relationship of sleep and HRQoL. Furthermore, parents significantly
      underestimate sleep disturbances and overestimate HRQoL in their children.

PMID- 22969732
TI  - Combination of Modafinil and d-amphetamine for the Treatment of Cocaine
      Dependence: A Preliminary Investigation.
AB  - BACKGROUND: Two stimulant medications, modafinil and d-amphetamine, when tested
      individually, have shown safety and efficacy for treatment of cocaine addiction.
      We hypothesized that the combination of modafinil and d-amphetamine, at low
      doses, would show equivalent or greater benefit in reducing cocaine use compared
      to higher doses of each individual medication or placebo. METHODS: Sixteen week,
      randomized, parallel-group design with four treatment arms comparing placebo to
      modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg.
      Primary outcome variables, retention and cocaine use, were analyzed on the sample
      of 73 participants who received the first dose of the study medication. RESULTS:
      Retention rates did not differ between groups and were generally low, with 40%
      remaining in treatment at week 12 and 20% at week 16. Participants receiving the
      combination of modafinil and d-amphetamine showed a trend of increased cocaine
      use over time with a corresponding low Bayesian probability of benefit (33%).
      Relatively better cocaine outcomes were observed in the placebo and d-amphetamine
      only groups. The study medications were generally well-tolerated with few adverse
      effects, yet rates of adherence were suboptimal (<=80%). CONCLUSION: Data from
      this preliminary investigation fail to provide evidential support for conducting
      a larger study of this dual-agonist medication combination for treatment of
      cocaine dependence.

PMID- 22969733
TI  - Transcranial direct current stimulation and behavioral models of smoking
      addiction.
AB  - While few studies have applied transcranial direct current stimulation (tDCS) to
      smoking addiction, existing work suggests that the intervention holds promise for
      altering the complex system by which environmental cues interact with cravings to
      drive behavior. Imaging and repetitive transcranial magnetic stimulation studies
      suggest that increased dorsolateral prefrontal cortex (DLPFC) activation and
      integrity may be associated with increased resistance to smoking cues. Anodal
      tDCS of the DLPFC, believed to boost activation, reduces cravings in response to
      these cues. The finding that noninvasive stimulation modifies cue induced
      cravings has profound implications for understanding the processes underlying
      addiction and relapse. tDCS can also be applied to probe mechanisms underlying
      and supporting nicotine addiction, as was done in a pharmacologic study that
      applied nicotine, tDCS, and TMS paired associative stimulation to find that
      stopping nicotine after chronic use induces a reduction in plasticity, causing
      difficulty in breaking free from association between cues and cravings. This mini
      review will place studies that apply tDCS to smokers in the context of research
      involving the neural substrates of nicotine addiction.

PMID- 22969734
TI  - Learning, memory, and transcranial direct current stimulation.
AB  - Transcranial direct current stimulation (tDCS) has been the subject of many
      studies concerning its possible cognitive effects. One of the proposed mechanisms
      of action for neuromodulatory techniques, such as transcranial magnetic
      stimulation and tDCS is induction of long-term potentiation (LTP) and long-term
      depression (LTD)-like phenomena. LTP and LTD are also among the most important
      neurobiological processes involved in memory and learning. This fact has led to
      an immediate interest in the study of possible effects of tDCS on memory
      consolidation, retrieval, or learning of various tasks. This review analyses
      published articles describing beneficial or disruptive effects of tDCS on memory
      and learning in normal subjects. The most likely mechanisms underlying these
      effects are discussed.

PMID- 22969735
TI  - Resting state networks and consciousness: alterations of multiple resting state
      network connectivity in physiological, pharmacological, and pathological
      consciousness States.
AB  - In order to better understand the functional contribution of resting state
      activity to conscious cognition, we aimed to review increases and decreases in
      functional magnetic resonance imaging (fMRI) functional connectivity under
      physiological (sleep), pharmacological (anesthesia), and pathological altered
      states of consciousness, such as brain death, coma, vegetative state/unresponsive
      wakefulness syndrome, and minimally conscious state. The reviewed resting state
      networks were the DMN, left and right executive control, salience, sensorimotor,
      auditory, and visual networks. We highlight some methodological issues concerning
      resting state analyses in severely injured brains mainly in terms of hypothesis
      driven seed-based correlation analysis and data-driven independent components
      analysis approaches. Finally, we attempt to contextualize our discussion within
      theoretical frameworks of conscious processes. We think that this "lesion"
      approach allows us to better determine the necessary conditions under which
      normal conscious cognition takes place. At the clinical level, we acknowledge the
      technical merits of the resting state paradigm. Indeed, fast and easy
      acquisitions are preferable to activation paradigms in clinical populations.
      Finally, we emphasize the need to validate the diagnostic and prognostic value of
      fMRI resting state measurements in non-communicating brain damaged patients.

PMID- 22969736
TI  - From emotions to consciousness - a neuro-phenomenal and neuro-relational
      approach.
AB  - The James-Lange theory considers emotional feelings as perceptions of
      physiological body changes. This approach has recently resurfaced and modified in
      both neuroscientific and philosophical concepts of embodiment of emotional
      feelings. In addition to the body, the role of the environment in emotional
      feeling needs to be considered. I here claim that the environment has not merely
      an indirect and instrumental, i.e., modulatory role on emotional feelings via the
      body and its sensorimotor and vegetative functions. Instead, the environment may
      have a direct and non-instrumental, i.e., constitutional role in emotional
      feelings. This implies that the environment itself is constitutive of emotional
      feeling rather than the bodily representation of the environment. I call this the
      relational concept of emotional feeling. The present paper discusses recent data
      from neuroimaging that investigate emotions in relation to interoceptive
      processing and the brain's intrinsic activity. These data show the intrinsic
      linkage of interoceptive stimulus processing to both exteroceptive stimuli and
      the brain's intrinsic activity. This is possible only if the differences between
      intrinsic activity and intero- and exteroceptive stimuli is encoded into neural
      activity. Such relational coding makes possible the assignment of subjective and
      affective features to the otherwise objective and non-affective stimulus. I
      therefore consider emotions to be intrinsically affective and subjective as it is
      manifest in emotional feelings. The relational approach thus goes together with
      what may be described as neuro-phenomenal approach. Such neuro-phenomenal
      approach does not only inform emotions and emotional feeling but is also highly
      relevant to better understand the neuronal mechanisms underlying consciousness in
      general.

PMID- 22969737
TI  - From objects to landmarks: the function of visual location information in spatial
      navigation.
AB  - Landmarks play an important role in guiding navigational behavior. A host of
      studies in the last 15 years has demonstrated that environmental objects can act
      as landmarks for navigation in different ways. In this review, we propose a
      parsimonious four-part taxonomy for conceptualizing object location information
      during navigation. We begin by outlining object properties that appear to be
      important for a landmark to attain salience. We then systematically examine the
      different functions of objects as navigational landmarks based on previous
      behavioral and neuroanatomical findings in rodents and humans. Evidence is
      presented showing that single environmental objects can function as navigational
      beacons, or act as associative or orientation cues. In addition, we argue that
      extended surfaces or boundaries can act as landmarks by providing a frame of
      reference for encoding spatial information. The present review provides a concise
      taxonomy of the use of visual objects as landmarks in navigation and should serve
      as a useful reference for future research into landmark-based spatial navigation.

PMID- 22969738
TI  - The effect of visual distinctiveness on multiple object tracking performance.
AB  - Observers often need to attentively track moving objects. In everyday life, such
      objects are often visually distinctive. Previous studies have shown that tracking
      accuracy is increased when the targets contain a visual feature (e.g., a color)
      not possessed by the distractors. Conversely, a gain in tracking accuracy was not
      observed when the targets differed from the distractors by only a conjunction of
      features (Makovski and Jiang, 2009a). In this study we confirm that some
      conjunction targets have relatively little effect on tracking accuracy, but show
      that other conjunction targets can significantly aid tracking. For example,
      tracking accuracy is relatively high when the targets are small red squares and
      half the distractors are large red squares while the remaining distractors are
      small green squares. This seems to occur because the targets have a set of
      features (small and red) not shared by any one distractor. Attending to these
      features directs attention more to the targets than the distractors, thereby
      making the targets easier to track. Existing theories of attentive tracking
      cannot explain these results.

PMID- 22969739
TI  - The importance of being relevant.
AB  - This review aims at an understanding of the binding process by synthesizing the
      extant perspectives regarding binding. It begins with a consideration of the
      biological explanations of binding, viz., conjunctive coding, synchrony, and
      reentrant mechanisms. Thereafter binding is reviewed as a psychological process
      guided by top-down signals. The stages and types of binding proposed by various
      researchers are discussed in this section. The next section introduces Working
      Memory (WM) as the executive directing the top-down signals. After that it is
      described how WM works by selecting relevant sensory input, followed by a
      detailed consideration of the debate regarding objects vs. features with the
      conclusion that relevance is the key factor determining what is processed. The
      next section considers other factors affecting the selection of relevant input.
      Then, we shift focus to describe what happens to irrelevant input - whether it is
      discarded at the outset or is gradually inhibited, and whether inhibition is a
      perceptual or post-perceptual process. The concluding section describes the
      process of binding as currently understood on the basis of the literature
      included in the review. To summarize, it appears that initially the "object" is
      conceptualized as an instantaneous bundle of all features. However, only relevant
      features of stimuli are gradually integrated to form a stable representation of
      the object. Concomitantly, irrelevant features are removed from the object
      representations. Empirical evidence suggests that the inhibition of irrelevant
      features occurs over time and is presumably a process within WM.

PMID- 22969740
TI  - True and False DRM Memories: Differences Detected with an Implicit Task.
AB  - Memory is prone to illusions. When people are presented with lists of words
      associated with a non-presented critical lure, they produce a high level of false
      recognitions (false memories) for non-presented related stimuli
      indistinguishable, at the explicit level, from presented words (DRM paradigm). We
      assessed whether true and false DRM memories can be distinguished at the implicit
      level by using the autobiographical IAT (aIAT), a novel method based on indirect
      measures that permits to detect true autobiographical events encoded in the
      respondent's mind/brain. In our experiment, after a DRM task participants
      performed two aIATs: the first aimed at testing implicit memory for presented
      words (true-memories aIAT) and the second aimed at evaluating implicit memory for
      critical lures (false-memories aIAT). Specifically, the two aIATs assessed the
      association of presented words and critical lures with the logical dimension
      "true." Results showed that the aIAT detected a greater association of presented
      words than critical lures with the logical dimension "true." This result
      indicates that although true and false DRM memories are indistinguishable at the
      explicit level a different association of the true and false DRM memories with
      the logical dimension "true" can be detected at the implicit level, and suggests
      that the aIAT may be a sensitive instrument to detect differences between true
      and false DRM memories.

PMID- 22969741
TI  - The role of affect in attentional functioning for younger and older adults.
AB  - Although previous research has shown that positive affect (PA) and negative
      affect (NA) modulate attentional functioning in distinct ways, few studies have
      considered whether the links between affect and attentional functioning may vary
      as a function of age. Using the Attention Network Test (Fan et al., 2002), we
      tested whether participants' current state of PA and NA influenced distinct
      attentional functions (i.e., alerting, orienting, and executive attention) and
      how the relationships between affective states and attentional functioning differ
      in younger (18-25 years) and older (60-85 years) age groups. While there were age
      differences in alerting efficiency, these age differences were mediated by PA,
      indicating that the higher state PA found in older adults may contribute to age
      differences in alerting. Furthermore, age group moderated the relationship
      between PA and orienting as well as NA and orienting. That is, higher levels of
      PA and lower levels of NA were associated with enhanced orienting efficiency in
      older adults. Neither PA nor NA had any influence on executive attention. The
      current results suggest that PA and NA may influence attentional functioning in
      distinct ways, but that these patterns may depend on age groups.

PMID- 22969742
TI  - Asynchrony in visual consciousness and the possible involvement of attention.
AB  - When subjects are asked to perceptually bind rapidly alternating color and motion
      stimuli, the pairings they report are different from the ones actually occurring
      in physical reality. A possible explanation for this misbinding is that the time
      necessary for perception is different for different visual attributes. Such an
      explanation is in logical harmony with the fact that the visual brain is
      characterized by different, functionally specialized systems, with different
      processing times for each; this type of organization naturally leads to different
      perceptual times for the corresponding attributes. In the present review, the
      experimental findings supporting perceptual asynchrony are presented, together
      with the original theoretical explanation behind the phenomenon and its
      implication for visual consciousness. Alternative theoretical views and
      additional experimental facts concerning perceptual misbinding are also reviewed,
      with a particular emphasis given to the role of attention. With few exceptions,
      most theories converge on the idea that the observed misbinding reflects a
      difference in perception times, which is in turn due to differences in neuronal
      processing times for different attributes within the brain. These processing time
      differences have been attributed to several different factors, attention
      included, with the possibility of co-existence between them.

PMID- 22969743
TI  - Abacus in the brain: a longitudinal functional MRI study of a skilled abacus user
      with a right hemispheric lesion.
AB  - The abacus, a traditional physical calculation device, is still widely used in
      Asian countries. Previous behavioral work has shown that skilled abacus users
      perform rapid and precise mental arithmetic by manipulating a mental
      representation of an abacus, which is based on visual imagery. However, its
      neurophysiological basis remains unclear. Here, we report the case of a patient
      who was a good abacus user, but transiently lost her "mental abacus" and superior
      arithmetic performance after a stroke owing to a right hemispheric lesion
      including the dorsal premotor cortex (PMd) and inferior parietal lobule (IPL).
      Functional magnetic resonance imaging experiments were conducted 6 and 13 months
      after her stroke. In the mental calculation task, her brain activity was shifted
      from the language-related areas, including Broca's area and the left dorsolateral
      prefrontal and IPLs, to the visuospatial-related brain areas including the left
      superior parietal lobule (SPL), according to the recovery of her arithmetic
      abilities. In the digit memory task, activities in the bilateral SPL, and right
      visual association cortex were also observed after recovery. The shift of brain
      activities was consistent with her subjective report that she was able to shift
      the calculation strategy from linguistic to visuospatial as her mental abacus
      became stable again. In a behavioral experiment using an interference paradigm, a
      visual presentation of an abacus picture, but not a human face picture,
      interfered with the performance of her digit memory, confirming her use of the
      mental abacus after recovery. This is the first case report on the impairment of
      the mental abacus by a brain lesion and on recovery-related brain activity. We
      named this rare case "abacus-based acalculia." Together with previous
      neuroimaging studies, the present result suggests an important role for the PMd
      and parietal cortex in the superior arithmetic ability of abacus users.

PMID- 22969744
TI  - Addressing motivation in globesity treatment: a new challenge for clinical
      psychology.

PMID- 22969745
TI  - Self-controlled feedback facilitates motor learning in both high and low activity
      individuals.
AB  - The purpose of this study was to determine if high and low activity individuals
      differed in terms of the effects of self-controlled feedback on the performance
      and learning of a movement skill. The task consisted of a blindfolded beanbag
      toss using the non-preferred arm. Participants were pre-screened according to
      their physical activity level using the International Physical Activity
      Questionnaire. An equal number of high activity (HA) and low activity (LA)
      participants were assigned to self-control (SC) and yoked (YK) feedback
      conditions, creating four groups: Self-Control-High Activity; Self-Control-Low
      Activity; Yoked-High Activity; and Yoked-Low Activity. SC condition participants
      were provided feedback whenever they requested it, while YK condition
      participants received feedback according to a schedule created by their SC
      counterpart. Results indicated that the SC condition was more accurate than the
      YK condition during acquisition and transfer phases, and the HA condition was
      more accurate than the LA condition during all phases of the experiment. A post
      training questionnaire indicated that participants in the SC condition asked for
      feedback mostly after what they perceived to be "good" trials; those in the YK
      condition indicated that they would have preferred to receive feedback after
      "good" trials. This study provided further support for the advantages of self
      controlled feedback when learning motor skills, additionally showing benefits for
      both active and less active individuals. The results suggested that the provision
      of self-controlled feedback to less active learners may be a potential avenue to
      teaching motor skills necessary to engage in greater amounts of physical
      activity.

PMID- 22969746
TI  - Advancing Our Understanding of the Link between Statistical Learning and Language
      Acquisition: The Need for Longitudinal Data.
AB  - Mastery of language can be a struggle for some children. Amongst those that
      succeed in achieving this feat there is variability in proficiency. Cognitive
      scientists remain intrigued by this variation. A now substantial body of research
      suggests that language acquisition is underpinned by a child's capacity for
      statistical learning (SL). Moreover, a growing body of research has demonstrated
      that variability in SL is associated with variability in language proficiency.
      Yet, there is a striking lack of longitudinal data. To date, there has been no
      comprehensive investigation of whether a capacity for SL in young children is, in
      fact, associated with language proficiency in subsequent years. Here we review
      key studies that have led to the need for this longitudinal research. Advancing
      the language acquisition debate via longitudinal research has the potential to
      transform our understanding of typical development as well as disorders such as
      autism, specific language impairment, and dyslexia.

PMID- 22969747
TI  - The Association between Symptoms, Pain Coping Strategies, and Physical Activity
      Among People with Symptomatic Knee and Hip Osteoarthritis.
AB  - Effective use of coping strategies by people with chronic pain conditions is
      associated with better functioning and adjustment to chronic disease. Although
      the effects of coping on pain have been well studied, less is known about how
      specific coping strategies relate to actual physical activity patterns in daily
      life. The purpose of this study was to evaluate how different coping strategies
      relate to symptoms and physical activity patterns in a sample of adults with knee
      and hip osteoarthritis (OA; N = 44). Physical activity was assessed by wrist-worn
      accelerometry; coping strategy use was assessed by the Chronic Pain Coping
      Inventory. We hypothesized that the use of coping strategies that reflect
      approach behaviors (e.g., Task Persistence), would be associated with higher
      average levels of physical activity, whereas avoidance coping behaviors (e.g.,
      Resting, Asking for Assistance, Guarding) and Pacing would be associated with
      lower average levels of physical activity. We also evaluated whether coping
      strategies moderated the association between momentary symptoms (pain and
      fatigue) and activity. We hypothesized that higher levels of approach coping
      would be associated with a weaker association between symptoms and activity
      compared to lower levels of this type of coping. Multilevel modeling was used to
      analyze the momentary association between coping and physical activity. We found
      that higher body mass index, fatigue, and the use of Guarding were significantly
      related to lower activity levels, whereas Asking for Assistance was significantly
      related to higher activity levels. Only Resting moderated the association between
      pain and activity. Guarding, Resting, Task Persistence, and Pacing moderated the
      association between fatigue and activity. This study provides an initial
      understanding of how people with OA cope with symptoms as they engage in daily
      life activities using ecological momentary assessment and objective physical
      activity measurement.

PMID- 22969748
TI  - MIR141 Expression Differentiates Hashimoto Thyroiditis from PTC and Benign
      Thyrocytes in Irish Archival Thyroid Tissues.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in
      length that function as regulators of gene expression. Dysregulation of miRNAs
      has been associated with initiation and progression of oncogenesis in humans. Our
      group has previously described a unique miRNA expression signature, including the
      MIR200 family member MIR141, which can differentiate papillary thyroid cancer
      (PTC) cell lines from a control thyroid cell line. An investigation into the
      expression of MIR141 in a series of archival thyroid malignancies [n = 140;
      classic PTC (cPTC), follicular variant PTC, follicular thyroid carcinoma,
      Hashimoto thyroiditis (HT), or control thyrocytes] was performed. Each cohort had
      a minimum of 20 validated samples surgically excised within the period 1980-2009.
      A subset of the HT and cPTC cohorts (n = 3) were also analyzed for expression of
      TGFbetaR1, a key member of the TGFbeta pathway and known target of MIR141. Laser
      capture microdissection was used to specifically dissect target cells from
      formalin-fixed paraffin-embedded archival tissue. Thyrocyte- and lymphocyte
      specific markers (TSHR and LSP1, respectively), confirmed the integrity of cell
      populations in the HT cohort. RNA was extracted and quantitative RT-PCR was
      performed using comparative CT (DeltaDeltaCT) analysis. Statistically significant
      (p < 0.05) differential expression profiles of MIR141 were found between tissue
      types. HT samples displayed significant downregulation of MIR141 compared to both
      cPTC and control thyrocytes. Furthermore, TGFbetaR1 expression was detected in
      cPTC samples but not in HT thyrocytes. It is postulated that the downregulation
      of this miRNA is due, at least in part, to its involvement in regulating the
      TGFbeta pathway. This pathway is exquisitely involved in T-cell autoimmunity and
      has previously been linked with HT. In conclusion, HT epithelium can be
      distinguished from cPTC epithelium and control epithelium based on the relative
      expression of MIR141.

PMID- 22969749
TI  - Decoding high Gonadotropin-releasing hormone pulsatility: a role for GnRH
      receptor coupling to the cAMP pathway?
AB  - The gonadotropin-releasing hormone (GnRH) pulsatile pattern is critical for
      appropriate regulation of gonadotrope activity but only little is known about the
      signaling mechanisms by which gonadotrope cells decode such pulsatile pattern.
      Here, we review recent lines of evidence showing that the GnRH receptor (GnRH-R)
      activates the cyclic AMP (cAMP) pathway in gonadotrope cells, thus ending a long
      lasting controversy. Interestingly, coupling of GnRH-R to the cAMP pathway as
      well as induction of nitric oxide synthase 1 (NOS1) or follistatin through this
      signaling pathway take place preferentially under high GnRH pulsatility. The
      preovulatory surge of GnRH in vivo is indeed associated with an important
      increase of pituitary cAMP and NOS1 expression levels, both being markedly
      inhibited by treatment with a GnRH antagonist. Altogether, this suggests that due
      to its atypical structure and desensitization properties, the GnRH-R may continue
      to signal through the cAMP pathway under conditions inducing desensitization for
      most other receptors. Such a mechanism may contribute to decode high GnRH
      pulsatile pattern and enable gonadotrope cell plasticity during the estrus cycle.

PMID- 22969750
TI  - A tale with a Twist: a developmental gene with potential relevance for metabolic
      dysfunction and inflammation in adipose tissue.
AB  - The Twist proteins (Twist-1 and -2) are highly conserved developmental proteins
      with key roles for the transcriptional regulation in mesenchymal cell lineages.
      They belong to the super-family of bHLH proteins and exhibit bi-functional roles
      as both activators and repressors of gene transcription. The Twist proteins are
      expressed at low levels in adult tissues but may become abundantly re-expressed
      in cells undergoing malignant transformation. This observation prompted extensive
      research on the roles of Twist proteins in cancer progression and metastasis.
      Very recent studies indicate a novel role for Twist-1 as a potential regulator of
      adipose tissue (AT) remodeling and inflammation. Several studies suggested that
      developmental genes are important determinants of obesity, fat distribution and
      remodeling capacity of different adipose depots. Twist-1 is abundantly and
      selectively expressed in the adult AT and its constitutive expression is
      significantly higher in subcutaneous (SAT) vs. visceral (VAT) fat in both mice
      and humans. Moreover, Twist1 expression is strongly correlated with BMI and
      insulin resistance in humans. However, the functional roles and transcriptional
      downstream targets of Twist1 in AT are largely unexplored. The purpose of this
      review is to highlight the major findings related to Twist1 expression in
      different fat depots and cellular components of AT and to discuss the potential
      mechanisms suggesting a role for Twist1 in AT metabolism, inflammation and
      remodeling.

PMID- 22969751
TI  - Insulin-Producing Cells in the Drosophila Brain also Express Satiety-Inducing
      Cholecystokinin-Like Peptide, Drosulfakinin.
AB  - Regulation of meal size and assessing the nutritional value of food are two
      important aspects of feeding behavior. The mechanisms that regulate these two
      aspects have not been fully elucidated in Drosophila. Diminished signaling with
      insulin-like peptides Drosophila insulin-like peptides (DILPs) affects food
      intake in flies, but it is not clear what signal(s) mediates satiety. Here we
      investigate the role of DILPs and drosulfakinins (DSKs), cholecystokinin-like
      peptides, as satiety signals in Drosophila. We show that DSKs and DILPs are co
      expressed in insulin-producing cells (IPCs) of the brain. Next we analyzed the
      effects of diminishing DSKs or DILPs employing the Gal4-UAS system by (1)
      diminishing DSK-levels without directly affecting DILP levels by targeted Dsk
      RNAi, either in all DSK-producing cells (DPCs) or only in the IPCs or (2)
      expressing a hyperpolarizing potassium channel to inactivate either all the DPCs
      or only the IPCs, affecting release of both peptides. The transgenic flies were
      assayed for feeding and food choice, resistance to starvation, and for levels of
      Dilp and Dsk transcripts in brains of fed and starved animals. Diminishment of
      DSK in the IPCs alone is sufficient to cause defective regulation of food intake
      and food choice, indicating that DSK functions as a hormonal satiety signal in
      Drosophila. Quantification of Dsk and Dilp transcript levels reveals that
      knockdown of either peptide type affects the transcript levels of the other,
      suggesting a possible feedback regulation between the two signaling pathways. In
      summary, DSK and DILPs released from the IPCs regulate feeding, food choice and
      metabolic homeostasis in Drosophila in a coordinated fashion.

PMID- 22969752
TI  - Stratified active archaeal communities in the sediments of Jiulong River estuary,
      China.
AB  - Here the composition of total and active archaeal communities in a sediment core
      of Jiulong River estuary at Fujian Province, Southern China was reported.
      Profiles of CH(4) and SO(2-) (4) concentrations from the sediment core indicated
      the existence of a sulfate-methane transition zone (SMTZ) in which sulfate
      reduction-coupled anaerobic oxidation of methane (AOM) occurs. Accordingly, three
      sediment layers (16-18.5 cm, 71-73.5 cm, and 161-163.5 cm) from the 1.2 m
      sediment core were sectioned and named top, middle and bottom, respectively.
      Total DNA and RNA of each layer were extracted and used for clone libraries and
      sequence analysis of 16S rRNA genes, the reverse transcription (RT)-PCR products
      of 16S rRNA and methyl CoM reductase alpha subunit (mcrA) genes. Phylogenetic
      analysis indicated that archaeal communities of the three layers were dominated
      by the Miscellaneous Crenarchaeotal Group (MCG) whose ecological functions were
      still unknown. The MCG could be further divided into seven subgroups, named MCG
      A, B, C, D, E, F, and G. MCG-A and MCG-G were the most active groups in the
      estuarine sediments. Known anaerobic methanotrophic archaea (ANMEs) were only
      found as minor components in these estuarine archaeal communities. This study,
      together with the studies of deep subsurface sediments, would be a very good
      start point to target and compare the specific active archaeal groups and their
      roles in the dark, deep subsurface sediment environments.

PMID- 22969753
TI  - Engineering microbial chemical factories to produce renewable "biomonomers".
AB  - By applying metabolic engineering tools and strategies to engineer synthetic
      enzyme pathways, the number and diversity of commodity and specialty chemicals
      that can be derived directly from renewable feedstocks is rapidly and continually
      expanding. This of course includes a number of monomer building-block chemicals
      that can be used to produce replacements to many conventional plastic materials.
      This review aims to highlight numerous recent and important advancements in the
      microbial production of these so-called "biomonomers." Relative to naturally
      occurring renewable bioplastics, biomonomers offer several important advantages,
      including improved control over the final polymer structure and purity, the
      ability to synthesize non-natural copolymers, and allowing products to be
      excreted from cells which ultimately streamlines downstream recovery and
      purification. To highlight these features, a handful of biomonomers have been
      selected as illustrative examples of recent works, including polyamide monomers,
      styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their
      industrial penetration to date and end-product uses are also highlighted. Novel
      biomonomers such as these are ultimately paving the way toward new classes of
      renewable bioplastics that possess a broader diversity of properties than ever
      before possible.

PMID- 22969754
TI  - Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus
      macaques (Macaca fascicularis).
AB  - A recent study showed that the frequency of an antiretroviral factor TRIM5 gene
      derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies
      widely according to the particular habitat examined. However, whether the
      findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques
      is still uncertain because the previous data were obtained with captive monkeys
      in breeding and rearing facilities. Here, we characterized the TRIM5 gene in
      cynomolgus macaques captured in the wild, and found that the frequency of the
      TRIMCyp allele was comparable to those in captive monkeys. This suggests that the
      previous results with captive monkeys do indeed reflect the natural allele
      frequency and that breeding and rearing facilities may not affect the frequency
      of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp
      in wild macaques from the Philippines was significantly lower than in captive
      ones, suggesting that it is advantageous for wild monkeys to possess the major
      haplotype of TRIMCyp. Overall, our results add to our understanding of the
      geographic and genetic prevalence of cynomolgus macaque TRIMCyp.

PMID- 22969755
TI  - Light gradients and optical microniches in coral tissues.
AB  - Light quantity and quality are among the most important factors determining the
      physiology and stress response of zooxanthellate corals. Yet, almost nothing is
      known about the light field that Symbiodinium experiences within their coral
      host, and the basic optical properties of coral tissue are unknown. We used
      scalar irradiance microprobes to characterize vertical and lateral light
      gradients within and across tissues of several coral species. Our results
      revealed the presence of steep light gradients with photosynthetically available
      radiation decreasing by about one order of magnitude from the tissue surface to
      the coral skeleton. Surface scalar irradiance was consistently higher over polyp
      tissue than over coenosarc tissue in faviid corals. Coral bleaching increased
      surface scalar irradiance by ~150% (between 500 and 700 nm) relative to a healthy
      coral. Photosynthesis peaked around 300 MUm within the tissue, which corresponded
      to a zone exhibiting strongest depletion of scalar irradiance. Deeper coral
      tissue layers, e.g., ~1000 MUm into aboral polyp tissues, harbor optical
      microniches, where only ~10% of the incident irradiance remains. We conclude that
      the optical microenvironment of corals exhibits strong lateral and vertical
      gradients of scalar irradiance, which are affected by both tissue and skeleton
      optical properties. Our results imply that zooxanthellae populations inhabit a
      strongly heterogeneous light environment and highlight the presence of different
      optical microniches in corals; an important finding for understanding the
      photobiology, stress response, as well as the phenotypic and genotypic plasticity
      of coral symbionts.

PMID- 22969756
TI  - Phage-Like Streptococcus pyogenes Chromosomal Islands (SpyCI) and Mutator
      Phenotypes: Control by Growth State and Rescue by a SpyCI-Encoded Promoter.
AB  - We recently showed that a prophage-like Streptococcus pyogenes chromosomal island
      (SpyCI) controls DNA mismatch repair and other repair functions in M1 genome
      strain SF370 by dynamic excision and reintegration into the 5' end of mutL in
      response to growth, causing the cell to alternate between a wild type and mutator
      phenotype. Nine of the 16 completed S. pyogenes genomes contain related SpyCI
      integrated into the identical attachment site in mutL, and in this study we
      examined a number of these strains to determine whether they also had a mutator
      phenotype as in SF370. With the exception of M5 genome strain Manfredo, all
      demonstrated a mutator phenotype as compared to SpyCI-free strain NZ131. The
      integrase gene (int) in the SpyCIM5 contains a deletion that rendered it
      inactive, and this deletion predicts that Manfredo would have a pronounced
      mutator phenotype. Remarkably, this was found not to be the case, but rather a
      cryptic promoter within the int ORF was identified that ensured constitutive
      expression of mutL and the downstream genes encoded on the same mRNA, providing a
      striking example of rescue of gene function following decay of a mobile genetic
      element. The frequent occurrence of SpyCI in the group A streptococci may
      facilitate bacterial survival by conferring an inducible mutator phenotype that
      promotes adaptation in the face of environmental challenges or host immunity.

PMID- 22969757
TI  - Spatial and temporal scales of aquatic bacterial beta diversity.
AB  - Understanding characteristic variation in aquatic bacterial community composition
      (BCC) across space and time can inform us about processes driving community
      assembly and the ability of bacterial communities to respond to perturbations. In
      this study, we synthesize BCC data from north temperate lakes to evaluate our
      current understanding of how BCC varies across multiple scales in time and space.
      A hierarchy of average similarity emerged with the highest similarity found among
      samples collected within the same lake, especially within the same basin,
      followed by similarity among samples collected through time within the same lake,
      and finally similarity among samples collected from different lakes. Using decay
      of similarity across time and space, we identified equivalent temporal (1 day)
      and spatial (10 m) scales of BCC variation. Finally, we identify an intriguing
      pattern of contrasting patterns of intra- and inter-annual BCC variation in two
      lakes. We argue our synthesis of spatio-temporal variation of aquatic BCC informs
      expectations for the response of aquatic bacterial communities to perturbation
      and environmental change. However, further long-term temporal observations will
      be needed to develop a general understanding of inter-annual BCC variation and
      our ability to use aquatic BCC as a sensitive metric of environmental change.

PMID- 22969758
TI  - Identifying viral parameters from in vitro cell cultures.
AB  - Current in vitro cell culture studies of viral replication deliver detailed time
      courses of several virological variables, like the amount of virions and the
      number of target cells, measured over several days of the experiment. Each of
      these time points solely provides a snap-shot of the virus infection kinetics and
      is brought about by the complex interplay of target cell infection, and viral
      production and cell death. It remains a challenge to interpret these data
      quantitatively and to reveal the kinetics of these underlying processes to
      understand how the viral infection depends on these kinetic properties. In order
      to decompose the kinetics of virus infection, we introduce a method to
      "quantitatively" describe the virus infection in in vitro cell cultures, and
      discuss the potential of the mathematical based analyses for experimental
      virology.

PMID- 22969759
TI  - What we are learning on HTLV-1 pathogenesis from animal models.
AB  - Isolated and identified more than 30 years ago, human T cell leukemia virus type
      1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma, an
      aggressive lymphoproliferative disease of activated CD4(+) T cells, and other
      inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic
      paraparesis. A variety of animal models have contributed to the fundamental
      knowledge of HTLV-1 transmission, pathogenesis, and to the design of novel
      therapies to treat HTLV-1-associated diseases. Small animal models (rabbits,
      rats, and mice) as well as large animal models (monkeys) have been utilized to
      significantly advance characterization of the viral proteins and of virus
      infected cells in the early steps of infection, as well as in the development of
      leukemogenic and immunopathogenic processes. Over the past two decades, the
      creation of new immunocompromised mouse strains that are robustly reconstituted
      with a functional human immune system (HIS) after being transplanted with human
      tissues or progenitor cells has revolutionized the in vivo investigation of viral
      infection and pathogenesis. Recent observations obtained in HTLV-1-infected
      humanized HIS mice that develop lymphomas provide the opportunity to study the
      evolution of the proviral clonality in human T cells present in different
      lymphoid organs. Current progress in the improvement of those humanized models
      will favor the testing of drugs and the development of targeted therapies against
      HTLV-1-associated diseases.

PMID- 22969760
TI  - Chloroplast symbiosis in a marine ciliate: ecophysiology and the risks and
      rewards of hosting foreign organelles.
AB  - Simultaneous use of both heterotrophic and autotrophic metabolism ("mixotrophy")
      is common among protists. Strombidium rassoulzadegani is a planktonic mixotrophic
      marine ciliate that saves chloroplasts from its algal food and obtains a
      nutritional subsidy via photosynthesis. Cultures from the northeast, northwest,
      and southwest Atlantic Ocean show similar numerical response parameters (maximum
      growth rate, food concentration at which growth is half its maximum, and
      threshold food concentration for growth), and some isolates have been maintained
      in vitro for over 3 years. This ciliate grows equally well when fed on the green
      alga Tetraselmis chui (strain PLY429) or the cryptophyte Rhodomonas lens (strain
      RHODO). It appears to be an obligate mixotroph, requiring both food and light to
      achieve positive growth, when feeding on either of these algae. However, it has
      also been grown for several weeks (>10 generations) heterotrophically on the
      dinoflagellate Prorocentrum minimum (strain EXUV) during which it grows better in
      dark than in light. In this paper, we review the ecology of S. rassoulzadegani,
      discuss some aspects of its photo- and feeding physiology, and speculate on
      benefits and costs to the ciliate of chloroplast symbiosis.

PMID- 22969761
TI  - The roles of acquired and innate immunity in human T-cell leukemia virus type 1
      mediated diseases.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL)
      and HTLV-1-associated myelopathy/tropical spastic paraparesis in small subsets of
      HTLV-1 carriers. HTLV-1-specific T-cell responses play critical roles in anti
      viral and anti-tumor host defense during HTLV-1 infections. Some HTLV-1 carriers
      exhibit selective loss or anergy of HTLV-1-specific T-cells at an asymptomatic
      stage. This is also observed in ATL patients and may therefore be an underlying
      risk factor of ATL in combination with elevated proviral loads. HTLV-1-specific T
      cells often recognize the viral oncoprotein Tax, indicating expression of Tax
      protein in vivo, although levels of HTLV-1 gene expression are known to be very
      low. A type-I interferon (IFN) response can be induced by HTLV-1-infected cells
      and suppresses HTLV-1 expression in vitro, suggesting a role of type-I IFN
      response in viral suppression and pathogenesis in vivo. Both acquired and innate
      immune responses control the status of HTLV-1-infected cells and could be the
      important determinants in the development of HTLV-1-mediated malignant and
      inflammatory diseases.

PMID- 22969762
TI  - Chromatinized Protein Kinase C-theta: Can It Escape the Clutches of NF-kappaB?
AB  - We recently provided the first description of a nuclear mechanism used by Protein
      Kinase C-theta (PKC-theta) to mediate T cell gene expression. In this mode, PKC
      theta tethers to chromatin to form an active nuclear complex by interacting with
      proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase
      LSD1, and the adaptor molecule 14-3-3zeta at regulatory regions of inducible
      immune response genes. Moreover, our genome-wide analysis identified many novel
      PKC-theta target genes and microRNAs implicated in T cell development,
      differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip
      analysis and have now identified a transcription factor motif containing NF
      kappaB binding sites that may facilitate recruitment of PKC-theta to chromatin at
      coding genes. Furthermore, NF-kappaB association with chromatin appears to be a
      prerequisite for the assembly of the PKC-theta active complex. In contrast, a
      distinct NF-kappaB-containing module appears to operate at PKC-theta targeted
      microRNA genes, and here NF-kappaB negatively regulates microRNA gene
      transcription. Our efforts are also focusing on distinguishing between the
      nuclear and cytoplasmic functions of PKCs to ascertain how these kinases may
      synergize their roles as both cytoplasmic signaling proteins and their functions
      on the chromatin template, together enabling rapid induction of eukaryotic genes.
      We have identified an alternative sequence within PKC-theta that appears to be
      important for nuclear translocation of this kinase. Understanding the molecular
      mechanisms used by signal transduction kinases to elicit specific and distinct
      transcriptional programs in T cells will enable scientists to refine current
      therapeutic strategies for autoimmune diseases and cancer.

PMID- 22969763
TI  - Emerging Functions of RANKL in Lymphoid Tissues.
AB  - The tumor necrosis factor superfamily (TNFSF) members play pivotal roles in
      embryonic development of lymphoid tissue and their homeostasis. RANKL (Receptor
      activator of NF-kappaB ligand, also called TRANCE, TNFSF11) is recognized as an
      important player in bone homeostasis and lymphoid tissue formation. In its
      absence bone mass control is deregulated and lymph nodes fail to develop. While
      its function in bone is well described, there is still little functional insight
      into the action of RANKL in lymphoid tissue development and homeostasis. Here we
      provide an overview of the known functions of RANKL, its signaling receptor RANK
      and its decoy receptor OPG from the perspective of lymphoid tissue development
      and immune activation in the mouse. Expressed by the hematopoietic lymphoid
      tissue inducing (LTi) cells and the mesenchymal lymphoid tissue organizer (LTo)
      cells, RANKL was shown to stimulate Lymphotoxin (LT) expression and to be
      implicated in LTi cell accumulation. Our recent finding that RANKL also triggers
      proliferation of adult lymph node stroma suggests that RANKL may furthermore
      directly activate LTo cells. Beyond bone, the RANKL-RANK-OPG triad plays
      important roles in immunobiology that are waiting to be unraveled.

PMID- 22969764
TI  - IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on
      the Cellular Levels of FOXP3 as Well as of Four Transcription Factors of  T Cell
      Activation.
AB  - The human CD4(+)FOXP3(+) T cell population is heterogeneous and consists of
      various subpopulations which remain poorly defined. Anergy and suppression are
      two main functional characteristics of FOXP3(+)Treg cells. We used the anergic
      behavior of FOXP3(+)Treg cells for a better discrimination and characterization
      of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing
      cells within the memory FOXP3(+) T cell population. In contrast to IL-2-non
      expressing FOXP3(+) cells, IL-2-expressing FOXP3(+) cells exhibit intermediate
      characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR,
      and Helios. Besides lower levels of FOXP3, they also have higher levels of the
      transcription factors NFATc2, c-Fos, NF-kappaBp65, and c-Jun. An approach
      combining flow cytometric measurements with statistical interpretation for
      quantitative transcription factor analysis suggests that the physiological
      expression levels not only of FOXP3 but also of NFATc2, c-Jun, c-Fos, and NF
      kappaBp65 are limiting for the decision whether IL-2 is expressed or not in
      activated peripheral human memory FOXP3(+) cells. These findings demonstrate that
      concomitant high levels of NFATc2, c-Jun, c-Fos, and NF-kappaBp65 lead in
      addition to potential IL-2 expression in those FOXP3(+) cells with low levels of
      FOXP3. We hypothesize that not only the level of FOXP3 expression but also the
      amounts of the four transcription factors studied represent determining factors
      for the anergic phenotype of FOXP3(+) Treg cells.

PMID- 22969765
TI  - Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency.
AB  - Genetic defects in the adenosine deaminase (ADA) gene are among the most common
      causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from
      lymphopenia, severely impaired cellular and humoral immunity, failure to thrive,
      and recurrent infections. Currently available therapeutic options for this
      otherwise fatal disorder include bone marrow transplantation (BMT), enzyme
      replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene
      therapy (HSC-GT). Although varying degrees of immune reconstitution can be
      achieved by these treatments, breakdown of tolerance is a major concern in ADA
      SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus,
      hemolytic anemia, and immune thrombocytopenia are frequently observed in milder
      forms of the disease. However, several reports document similar complications
      also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed
      repertoire and decreased immune functions have been implicated in autoimmunity
      observed in certain B-cell and/or T-cell immunodeficiencies, but it remains
      unclear to what extent specific mechanisms of tolerance are affected in ADA
      deficiency. Herein we provide an overview about ADA-SCID and the autoimmune
      manifestations reported in these patients before and after treatment. We also
      assess the value of the ADA-deficient mouse model as a useful tool to study both
      immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells
      we discuss the lymphocyte subpopulations particularly prone to contribute to the
      loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we
      address which aspects of immune dysregulation are specifically related to
      alterations in purine metabolism caused by the lack of ADA and the subsequent
      accumulation of metabolites with immunomodulatory properties.

PMID- 22969766
TI  - Autoreactive T Cells in Human Smokers is Predictive of Clinical Outcome.
AB  - Cross-sectional studies have suggested a role for activation of adaptive immunity
      in smokers with emphysema, but the clinical application of these findings has not
      been explored. Here we examined the utility of detecting autoreactive T cells as
      a screening tool for emphysema in an at-risk population of smokers. We followed
      156 former and current (ever)-smokers for 2 years to assess whether peripheral
      blood CD4 T cell cytokine responses to lung elastin fragments (EFs) could
      discriminate between those with and without emphysema, and to evaluate the
      relevance of autoreactive T cells to predict changes during follow-up in lung
      physiological parameters. Volunteers underwent baseline complete phenotypic
      assessment with pulmonary function tests, quantitative chest CT, yearly 6-min
      walk distance (6MWD) testing, and annual measurement of CD4 T cell cytokine
      responses to EFs. The areas under the receiver operating characteristic curve to
      predict emphysema for interferon gamma (IFN-gamma), and interleukin 6 (IL-6)
      responses to EFs were 0.81 (95% CI of 0.74-0.88) and 0.79 (95% CI of 0.72-0.86)
      respectively. We developed a dual cytokine enzyme-linked immunocell spot assay,
      the gamma-6 Spot, using CD4 T cell IFN-gamma and IL-6 responses and found that it
      discriminated emphysema with 90% sensitivity. After adjusting for potential
      confounders, the presence of autoreactive T cells was predictive of a decrease in
      6MWD over 2 years (decline in 6MWD, -19 m per fold change in IFN-gamma; P =
      0.026, and -26 m per fold change in IL-6; P = 0.003). In support of the human
      association studies, we cloned CD4 T cells with characteristic T helper (Th)1 and
      Th17 responses to EFs in the peripheral blood of ever-smokers with emphysema,
      confirming antigenicity of lung elastin in this population. These findings
      collectively suggest that the EF-specific autoreactive CD4 T cell assay, gamma-6
      Spot, could provide a non-invasive diagnostic tool with potential application to
      large-scale screening to discriminate emphysema in ever-smokers, and predict
      early relevant physiological outcomes in those at risk.

PMID- 22969768
TI  - Transcriptional regulation of the anti-inflammatory cytokine IL-10 in acquired
      immune cells.
AB  - Although the major role of the immune response is host defense from a wide range
      of potentially pathogenic microorganisms, excess immune responses can result in
      severe host damage. The host thus requires anti-inflammatory mechanisms to
      prevent reactivity to self. Interleukin-10 (IL-10) is a cytokine with broad anti
      inflammatory properties involved in the pathogenesis of various diseases. IL-10
      was originally described as a T helper (T(H)2) derived cytokine, but further
      studies indicated that IL-10 is expressed not only by many cells of the adaptive
      immune system, including T and B cells, but also by the innate immune cells,
      including dendritic cells (DCs), macrophages, mast cells, and natural killer (NK)
      cells. In addition, IL-10 can be induced in T(H)1 and T(H)17 cells by chronic
      inflammation as a system of feedback regulation. In this review, we focus on the
      molecular mechanisms underlying IL10 gene expression in adaptive immune cells and
      summarize the recent progresses in epigenetic and transcriptional regulation of
      the IL10 gene. Understanding the transcriptional regulatory events may help in
      the development of new strategies to control inflammatory diseases.

PMID- 22969769
TI  - Monosodium urate crystals induce extracellular DNA traps in neutrophils,
      eosinophils, and basophils but not in mononuclear cells.
AB  - Neutrophil extracellular traps (NETs) are fibers of extracellular DNA released
      from neutrophils due to overwhelming phagocytic stimuli. The function of NETs is
      to trap and kill microbes to avoid spreading of potential pathogens. NETs are
      formed after encounter with various gram-positive and -negative bacteria but also
      in response to mediators causing sterile inflammation like interleukin-8 (IL-8),
      tumor necrosis factor (TNF), and phorbol myristate acetate (PMA). Here we show
      the formation of NETs (NETting) in response to monosodium urate (MSU) crystals as
      further model for sterile inflammation. We identified monocytes, neutrophils, and
      eosinophils as MSU phagocytosing cells. Basophils did not take up the crystals,
      instead they upregulated their activation marker CD203c after contact with MSU.
      Nevertheless, MSU crystals induced extracellular trap formation also in
      basophils, like in eosinophils and neutrophils, which phagocytose the crystals.
      In contrast, monocytes do not form NETs despite uptake of the MSU crystals. In
      contrast to the canonical stimuli like bacteria and PMA, MSU-induced NETosis was
      not abrogated by plasma. Our data show that MSU crystals induce extracellular DNA
      trap formation in all three granulocytes lineages (NETs, EETs, and BETs) but not
      in monocytes, and DNA externalization does not necessitate the uptake of the
      crystals.

PMID- 22969767
TI  - Regulatory dendritic cells: there is more than just immune activation.
AB  - The immune system exists in a delicate equilibrium between inflammatory responses
      and tolerance. This unique feature allows the immune system to recognize and
      respond to potential threats in a controlled but normally limited fashion thereby
      preventing a destructive overreaction against healthy tissues. While the adaptive
      immune system was the major research focus concerning activation vs. tolerance in
      the immune system more recent findings suggest that cells of the innate immune
      system are important players in the decision between effective immunity and
      induction of tolerance or immune inhibition. Among immune cells of the innate
      immune system dendritic cells (DCs) have a special function linking innate immune
      functions with the induction of adaptive immunity. DCs are the primary
      professional antigen presenting cells (APCs) initiating adaptive immune
      responses. They belong to the hematopoietic system and arise from CD34(+) stem
      cells in the bone marrow. Particularly in the murine system two major subgroups
      of DCs, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) can be
      distinguished. DCs are important mediators of innate and adaptive immunity mostly
      due to their remarkable capacity to present processed antigens via major
      histocompatibility complexes (MHC) to T cells and B cells in secondary lymphoid
      organs. A large body of literature has been accumulated during the last two
      decades describing which role DCs play during activation of T cell responses but
      also during the establishment and maintenance of central tolerance (Steinman et
      al., 2003). While the concept of peripheral tolerance has been clearly
      established during the last years, the role of different sets of DCs and their
      particular molecular mechanisms of immune deviation has not yet fully been
      appreciated. In this review we summarize accumulating evidence about the role of
      regulatory DCs in situations where the balance between tolerance and
      immunogenicity has been altered leading to pathologic conditions such as chronic
      inflammation or malignancies.

PMID- 22969770
TI  - TNF receptor family signaling in the development and functions of medullary
      thymic epithelial cells.
AB  - Thymic epithelial cells (TECs) provide the microenvironment required for the
      development of T cells in the thymus. A unique property of medullary thymic
      epithelial cells (mTECs) is their expression of a wide range of tissue-restricted
      self-antigens, critically regulated by the nuclear protein AIRE, which
      contributes to the selection of the self-tolerant T cell repertoire, thereby
      suppressing the onset of autoimmune diseases. The TNF receptor family (TNFRF)
      protein receptor activator of NF-kappaB (RANK), CD40 and lymphotoxin beta
      receptor (LtbetaR) regulate the development and functions of mTECs. The
      engagement of these receptors with their specific ligands results in the
      activation of the NF-kappaB family of transcription factors. Two NF-kappaB
      activation pathways, the classical and non-classical pathways, promote the
      development of mature mTECs induced by these receptors. Consistently, TNF
      receptor-associated factor (TRAF6), the signal transducer of the classical
      pathway, and NF-kappaB inducing kinase (NIK), the signal transducer of the non
      classical pathway, are essential for the development of mature mTECs. This review
      summarizes the current understanding of how the signaling by the TNF receptor
      family controls the development and functions of mTEC.

PMID- 22969771
TI  - Tight control - decision-making during T cell-vascular endothelial cell
      interaction.
AB  - Vascular endothelial cells (ECs) form the inner layer of blood vessels and exert
      crucial functions during immune reactions including coagulation, inflammation,
      and regulation of innate immunity. Importantly, ECs can interact with T cells in
      an antigen-specific, i.e., T cell receptor-dependent manner. In this review, we
      will discuss EC actions and reactions during acute inflammation and focus on the
      interaction of T cells with ECs at two vascular sites: the high endothelial
      venule (HEV) of lymph nodes, and the vascular lesion during transplant
      vasculopathy (TV). HEVs are characterized by a highly active endothelium that
      produces chemoattracting factors and expresses adhesion molecules to facilitate
      transit of lymphocytes into the lymph node (LN) parenchyma. Yet, T cell-EC
      interaction at this anatomical location results neither in T cell activation nor
      tolerization. In contrast, the endothelium at sites of chronic inflammation, such
      as solid organ transplants, can promote T cell activation by upregulation of
      major histocompatibility complex (MHC) and costimulatory molecules. Importantly,
      a major function of ECs in inflamed tissues must be the maintenance of vascular
      integrity including the efficient attenuation of effector T cells that may damage
      the vascular bed. Thus, antigen-specific T cell-EC interaction is characterized
      by a tightly controlled balance between immunological ignorance, immune
      activation, and tolerization.

PMID- 22969773
TI  - Narrowed Aortoseptal Angle Is Related to Increased Central Blood Pressure and
      Aortic Pressure Wave Reflection.
AB  - The left ventricular (LV) aortoseptal angle (ASA) decreases with age, and is
      associated with basal septal hypertrophy (septal bulge). Enhanced arterial
      pressure wave reflection is known to impact LV hypertrophy. We assessed whether
      ASA is related to central blood pressure (BP) and augmentation index (AI), a
      measure of the reflected pressure wave. We studied 75 subjects (age 62 +/- 16
      years; 66% female) who were referred for transthoracic echocardiography and had
      radial artery applanation tonometry within 24 h. Peripheral systolic BP (P-SBP),
      peripheral diastolic BP (P-DBP), and peripheral pulse pressure (P-PP) were
      obtained by sphygmomanometry. Central BPs (C-SBP, C-DBP, C-PP) and AI were
      derived from applanation tonometry. AI was corrected for heart rate (AI75). The
      basal septal wall thickness (SWT), mid SWT and ASA were measured using the
      parasternal long axis echocardiographic view. Mean ASA and AI75 were 117 +/- 11
      degrees  and 22 +/- 11%, respectively. ASA correlated with AI75 (r = -0.31, p <=
      0.01), C-SBP (r = -0.24, p = 0.04), C-PP (r = -0.29, p = 0.01), but only showed a
      trend towards significance with P-SBP (r = -0.2, p = 0.09) and P-PP (r = -0.21, p
      = 0.08). Interestingly, C-PP was correlated with basal SWT (r = 0.27, p = 0.02)
      but not with mid SWT (r = 0.19, p = 0.11). On multivariate linear regression
      analysis, adjusted for age, gender, weight, and mean arterial pressure, AI75 was
      an independent predictor of ASA (p = 0.02). Our results suggest that a narrowed
      ASA is related to increased pressure wave reflection and higher central BP.
      Further studies are needed to determine whether narrowed LV ASA is a cause or
      consequence of enhanced wave reflection and whether other factors are involved.

PMID- 22969772
TI  - A Single-Centre Study of Acute Cardiorenal Syndrome: Incidence, Risk Factors and
      Consequences.
AB  - OBJECTIVE: Cardiac and kidney diseases are common, and the impact of acute kidney
      injury (AKI) on patient outcome is well known. We aimed to investigate the
      incidence of acute cardiorenal syndrome (CRS) and the risk factors and outcomes
      associated with the disease.  METHODS: We conducted a retrospective cohort study
      comprising 289 patients with acute coronary syndrome (ACS) and acute
      decompensated heart failure (ADHF), examining the incidence of AKI defined
      according to the Acute Kidney Injury Network (AKIN) classification, the factors
      contributing to AKI, and the impact of AKI on in-hospital mortality and hospital
      re-admission.  RESULTS: Of 71 patients with AKI, 36 (50.7%) had ACS and 35 (49%)
      had ADHF. Overall in-hospital mortality was 5.5% (n = 16). Multivariate logistic
      regression identified the following independent predictors of AKI in male
      patients with ACS: previous myocardial infarction at age >65 years (OR 5.967, 95%
      CI 1.16-30.47, p = 0.03), chronic kidney disease (OR 3.72, 95% CI 1.31-16.61, p =
      0.01), and decreased hemoglobin levels (OR 0.684, 95% CI 0.53-0.88, p = 0.03). No
      variable was identified as an independent risk factor in ADHF patients. Kaplan
      Meier survival curves indicated that patients with ACS plus AKI had significantly
      higher in-hospital mortality (log rank = 0.007).  CONCLUSION: Acute CRS (type 1
      CRS) is more frequent in patients with ADHF and can be considered multifactorial.
      Although CRS is less frequent in ACS patients, it is associated with longer
      hospital stay and with higher in-hospital mortality. The heart-kidney interaction
      should be managed collaboratively between cardiologists and nephrologists to
      increase our knowledge and enhance clinical approaches.

PMID- 22969774
TI  - Percutaneous Transluminal Revascularization following an Angiotensin Receptor
      Blocker: Successful Treatment for Flash Pulmonary Edema and Hyponatremic
      Hypertensive Syndrome.
AB  - Either flash pulmonary edema or hyponatremic hypertensive syndrome has been
      described in renal artery stenosis. However, coexistence of these two disorders
      has never been previously reported. We describe a patient who presented with
      flash pulmonary edema and hyponatremic hypertensive syndrome associated with
      bilateral renal artery disease (one complete occlusion, one highly critical renal
      artery stenosis, the equivalent of unilateral stenosis of a solitary functioning
      kidney). His blood pressure, hyponatremia, and symptoms of acute heart failure
      were much improved by an angiotensin receptor blocker. After the procedure of
      percutaneous transluminal revascularization, his stenotic kidney function and
      serum sodium levels were completely restored.

PMID- 22969776
TI  - Loss of Estrogen Receptor alpha Signaling Leads to Insulin Resistance and Obesity
      in Young and Adult Female Mice.
AB  - BACKGROUND/AIMS: There are important sex-related differences in the prevalence of
      obesity, type 2 diabetes mellitus and cardiovascular disease. Indeed,
      premenopausal women have a lower prevalence of these conditions relative to age
      matched men. Estrogen participates in the modulation of insulin sensitivity,
      energy balance, and body composition. In this paper, we investigated the impact
      of estrogen signaling through estrogen receptor alpha (ERalpha) on systemic
      insulin sensitivity and insulin signaling in skeletal muscle.  METHODS: In 14-
      and 30-week-old female ERalpha knockout (ERalphaKO) mice and age-matched
      controls, we assessed insulin sensitivity by a euglycemic-hyperinsulinemic clamp
      and intraperitoneal glucose tolerance testing. Blood pressure was evaluated by
      tail cuff and telemetry. We studied ex vivo insulin-stimulated glucose uptake in
      skeletal muscle tissue, as well as insulin metabolic signaling molecule
      phosphorylation by immunoblotting and oxidative stress by immunostaining for 3
      nitrotyrosine.  RESULTS: Body weight was higher in ERalphaKO mice at 14 and 30
      weeks of age. At 30 weeks, intraperitoneal glucose tolerance testing and clamp
      results demonstrated impaired systemic insulin sensitivity in ERalphaKO mice.
      Insulin-stimulated glucose uptake in soleus was lower in ERalphaKO mice at both
      ages. The insulin receptor substrate 1/phosphatidylinositol 3-kinase association
      and the activation of protein kinase B were decreased in ERalphaKO mice, whereas
      immunostaining for 3-nitrotyrosine was increased.  CONCLUSIONS: Our data
      demonstrate a critical age-dependent role for estrogen signaling through ERalpha
      on whole-body insulin sensitivity and insulin metabolic signaling in skeletal
      muscle tissue. These findings have potential translational implications for the
      prevention and management of type 2 diabetes mellitus and cardiovascular disease
      in women, who are at increased risk for these conditions.

PMID- 22969775
TI  - On-versus Off-Pump Coronary Artery Bypass Grafting: No Difference in Early
      Postoperative Kidney Function Based on TNF-alpha or C-Reactive Protein.
AB  - BACKGROUND/AIMS: There are controversial data about renal function following off
      pump coronary artery bypass grafting (CABG). The present study aimed to evaluate
      renal function changes 24 h after on- and off-pump CABG, as well as renal
      function correlated with high-sensitivity C-reactive protein (hs-CRP) and tumor
      necrosis factor-alpha (TNF-alpha).  METHODS: Ninety patients with coronary artery
      disease referred to our center for CABG from July 2006 to November 2007 were
      enrolled in the study. Patients were equally and randomly divided in two groups,
      on- and off-pump. Serum levels of creatinine (Cr), blood urea nitrogen,
      creatinine clearance (CrCl), hs-CRP, and TNF-alpha were determined immediately
      before and 24 h after surgery.  RESULTS: Cr and CrCl changes after surgery were
      not significantly different between the two groups; however, blood urea nitrogen
      levels after surgery were significantly higher in the on-pump group (p = 0.035).
      No statistically significant difference was noted between the two groups in terms
      of changes in levels of hs-CRP and TNF-alpha (p = 0.350 and 0.805, respectively).
      The changes in CrCl levels had no significant correlation with hs-CRP and TNF
      alpha.  CONCLUSIONS: The early Cr and CrCl levels after surgery are not
      significantly different in on- and off-pump groups. The early renal function
      after on- or off-pump CABG is not correlated with the levels of inflammatory
      markers including hs-CRP and TNF-alpha.

PMID- 22969777
TI  - Relationship between Changes in Plasma Adiponectin Concentration and Insulin
      Sensitivity after Niacin Therapy.
AB  - BACKGROUND: Niaspan(r) (extended-release niacin) is a nicotinic acid formulation
      used to treat dyslipidemia in obese subjects. Niaspan binds to the GPR109A
      receptor in adipose tissue and stimulates adiponectin secretion, which should
      improve insulin sensitivity. However, Niaspan therapy often causes insulin
      resistance. The purpose of this study was to evaluate whether Niaspan-induced
      changes in plasma adiponectin concentration are associated with a blunting of
      Niaspan's adverse effect on insulin action in obese subjects with non-alcoholic
      fatty liver disease (NAFLD).  METHODS: A hyperinsulinemic-euglycemic clamp
      procedure was used to assess muscle insulin sensitivity before and after 16 weeks
      of Niaspan therapy in 9 obese subjects with NAFLD [age 43 +/- 5 years; BMI 35.1
      +/- 1.3 (means +/- SEM)].  RESULTS: Niaspan therapy did not affect body weight
      (99.1 +/- 4.2 vs. 100 +/- 4.4 kg) or percent body fat (37.8 +/- 2.5 vs. 37.0 +/-
      2.5%). However, Niaspan therapy caused a 22% reduction in insulin-mediated
      glucose disposal (p < 0.05). The deterioration in glucose disposal was inversely
      correlated with the Niaspan-induced increase in plasma adiponectin concentration
      (r = 0.67, p = 0.05).  CONCLUSIONS: These results demonstrate that Niaspan causes
      skeletal muscle insulin resistance, independent of changes in body weight or body
      fat, and the Niaspan-induced increase in plasma adiponectin concentration might
      partially ameliorate Niaspan's adverse effect on insulin action in obese subjects
      with NAFLD.

PMID- 22969778
TI  - Silent Ischemic Heart Disease in a Patient with Necrotizing Glomerulonephritis
      due to Wegener's Granulomatosis.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is a necrotizing vasculitis that mainly
      affects the respiratory tract and kidneys, but can also affect other systems such
      as the eye, joints, skin, muscles, nerves, and gastrointestinal tract. Cardiac
      involvement is traditionally believed to be rare. We report a patient with silent
      myocardial infarction (MI) and review previously reported cases showing this
      association.  METHODS: A Medline database search of cases published between
      January 1978 and July 2008 both in English and Spanish, reporting silent MI
      complicating WG, was conducted.  RESULTS: We describe a typical patient with WG
      who had both respiratory and renal involvement and died unexpectedly following a
      silent MI after a period of clinical improvement induced by treatment with
      prednisone and cyclophosphamide. We report necropsy findings and the association
      with 5 additional cases of WG with silent MI reported in the literature. 
      CONCLUSIONS: Clinicians should be aware of potential cardiac involvement due to
      WG. Careful evaluation of each patient, with or without cardiac symptoms, using
      ECG, echocardiogram, and myocardial enzymes is prudent.

PMID- 22969779
TI  - Regulation of Overnutrition-Induced Cardiac Inflammatory Mechanisms.
AB  - BACKGROUND: Unlike conventional beta-blockers, nebivolol, a third-generation beta
      adrenergic receptor blocker with vasodilator properties, promotes insulin
      sensitivity. Objective: The objective of this study was to determine whether
      nebivolol regulates overnutrition-induced activation of cardiac nutrient sensor
      kinases and inflammatory signaling.  METHODS: Young Zucker obese (ZO) rats, a
      rodent model for overnutrition, and age-matched Zucker lean rats were treated
      with nebivolol (10 mg/kg/day; 21 days) and cardiac function was monitored by
      echocardiography and pressure volume loop analysis. Activation status of nutrient
      sensor serine/threonine kinases mammalian target for rapamycin (mTOR), and p70
      S6kinase (S6K1) and S6K1-substrate RPS6, inflammatory marker Janus kinase 2
      (Jak2) and its substrate STAT1, and energy sensor AMP-dependent kinase (AMPK)
      were monitored by determining phosphorylation status of pSer(2448) of mTOR,
      pThr(389) of S6K1, pSer(235/236) of RPS6, pTyr(1007/1008) of Jak2, pTyr(701) of
      STAT1, and pThr(172) of AMPK, respectively.  RESULTS: Nebivolol reduced weight
      and improved cardiac function of ZO rats as shown by improvements in the
      myocardial performance index and a decrease in the diastolic parameter tau (tau),
      the time constant of isovolumic relaxation. Nebivolol also attenuated excessive
      activation of the nutrient sensor kinases mTOR and S6K1 and their substrate RPS6
      as well as the inflammatory marker Jak2 and substrate STAT1 in ZO myocardium (p <
      0.05). Moreover, nebivolol reversed suppression of the energy sensor kinase AMPK
      in ZO hearts (p < 0.05).  CONCLUSION: We report for the first time that nebivolol
      regulates overnutrition-induced activation of cardiac mTOR and Jak/STAT signaling
      and reverses suppression of AMPK. Since it also suppresses weight gain, nebivolol
      appears effective in the treatment of overnutrition-related cardiac inflammation
      and diastolic dysfunction.

PMID- 22969780
TI  - Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide
      Metabolites and Plasma Isoprostanes in African-Americans.
AB  - BACKGROUND: Vitamin D deficiency and secondary rises in parathyroid hormone (PTH)
      are highly prevalent in obese African-Americans. Endothelial dysfunction related
      to oxidative stress is more common in African-Americans compared to whites.
      Currently, the association of vitamin D (25-hydroxyvitamin D, 25-OH D) and PTH to
      nitric oxide metabolites (NOx) - nitrate and nitrite - and oxidative stress in
      African-Americans is unknown. Objective: A cross-sectional design was utilized to
      determine the association of 25-OH D and PTH with urinary NOx (UNOx) (n = 101)
      and plasma isoprostanes (n = 125), an oxidative stress marker, in overweight
      (body mass index of 25-39.9), normotensive African-Americans aged >=35 years.
      Measurements: Multivariable linear regression analysis adjusted for age, sex,
      body mass index, and season was used to determine the relationship of 25-OH D and
      PTH to UNOx and isoprostanes. General linear models, adjusted for the same
      covariates, contrasted UNOx across three mutually exclusive vitamin D/PTH groups:
      (1) normal 25-OH D (51-249 nmol/l) and normal PTH (<=65 pg/ml); (2) low 25-OH D
      and normal PTH, and (3) low 25-OH D and high PTH.  RESULTS: 25-OH D was directly
      associated with UNOx before (p = 0.02) and after (p = 0.03) adjustment for PTH
      levels. A borderline significant association was observed between PTH and
      isoprostanes (p = 0.08). UNOx was 424, 290, and 270 MUmol/8 h, respectively,
      across vitamin D/PTH groups 1-3 (p = 0.08).  CONCLUSION: 25-OH D was directly
      associated with NO availability and PTH was positively, though borderline,
      associated with isoprostanes in overweight, normotensive adult African-Americans.

PMID- 22969781
TI  - Arabidopsis Myosin XI-K Localizes to the Motile Endomembrane Vesicles Associated
      with F-actin.
AB  - Plant myosins XI were implicated in cell growth, F-actin organization, and
      organelle transport, with myosin XI-K being a critical contributor to each of
      these processes. However, subcellular localization of myosins and the identity of
      their principal cargoes remain poorly understood. Here, we generated a
      functionally competent, fluorescent protein-tagged, myosin XI-K, and investigated
      its spatial distribution within Arabidopsis cells. This myosin was found to
      associate primarily not with larger organelles (e.g., Golgi) as was broadly
      assumed, but with endomembrane vesicles trafficking along F-actin. Subcellular
      localization and fractionation experiments indicated that the nature of myosin
      associated vesicles is organ- and cell type-specific. In leaves, a large
      proportion of these vesicles aligned and co-fractionated with a motile
      endoplasmic reticulum (ER) subdomain. In roots, non-ER vesicles were a dominant
      myosin cargo. Myosin XI-K showed a striking polar localization at the tips of
      growing, but not mature, root hairs. These results strongly suggest that a major
      mechanism whereby myosins contribute to plant cell physiology is vesicle
      transport, and that this activity can be regulated depending on the growth phase
      of a cell.

PMID- 22969782
TI  - Using the Yeast Three-Hybrid System to Identify Proteins that Interact with a
      Phloem-Mobile mRNA.
AB  - Heterografting and RNA transport experiments have demonstrated the long-distance
      mobility of StBEL5 RNA, its role in controlling tuber formation, and the function
      of the 503-nt 3' untranslated region (UTR) of the RNA in mediating transport.
      Because the 3' UTR of StBEL5 is a key element in regulating several aspects of
      RNA metabolism, a potato leaf cDNA library was screened using the 3' UTR of
      StBEL5 as bait in the yeast three-hybrid (Y3H) system to identify putative
      partner RNA-binding proteins (RBPs). From this screen, 116 positive cDNA clones
      were isolated based on nutrient selection, HIS3 activation, and lacZ induction
      and were sequenced and classified. Thirty-five proteins that were predicted to
      function in either RNA- or DNA-binding were selected from this pool. Seven were
      monitored for their expression profiles and further evaluated for their capacity
      to bind to the 3' UTR of StBEL5 using beta-galactosidase assays in the Y3H system
      and RNA gel-shift assays. Among the final selections were two RBPs, a zinc finger
      protein, and one protein, StLSH10, from a family involved in light signaling. In
      this study, the Y3H system is presented as a valuable tool to screen and verify
      interactions between target RNAs and putative RBPs. These results can shed light
      on the dynamics and composition of plant RNA-protein complexes that function to
      regulate RNA metabolism.

PMID- 22969783
TI  - PredPlantPTS1: A Web Server for the Prediction of Plant Peroxisomal Proteins.
AB  - Prediction of subcellular protein localization is essential to correctly assign
      unknown proteins to cell organelle-specific protein networks and to ultimately
      determine protein function. For metazoa, several computational approaches have
      been developed in the past decade to predict peroxisomal proteins carrying the
      peroxisome targeting signal type 1 (PTS1). However, plant-specific PTS1 protein
      prediction methods have been lacking up to now, and pre-existing methods
      generally were incapable of correctly predicting low-abundance plant proteins
      possessing non-canonical PTS1 patterns. Recently, we presented a machine learning
      approach that is able to predict PTS1 proteins for higher plants (spermatophytes)
      with high accuracy and which can correctly identify unknown targeting patterns,
      i.e., novel PTS1 tripeptides and tripeptide residues. Here we describe the first
      plant-specific web server PredPlantPTS1 for the prediction of plant PTS1 proteins
      using the above-mentioned underlying models. The server allows the submission of
      protein sequences from diverse spermatophytes and also performs well for mosses
      and algae. The easy-to-use web interface provides detailed output in terms of (i)
      the peroxisomal targeting probability of the given sequence, (ii) information
      whether a particular non-canonical PTS1 tripeptide has already been
      experimentally verified, and (iii) the prediction scores for the single C
      terminal 14 amino acid residues. The latter allows identification of predicted
      residues that inhibit peroxisome targeting and which can be optimized using site
      directed mutagenesis to raise the peroxisome targeting efficiency. The prediction
      server will be instrumental in identifying low-abundance and stress-inducible
      peroxisomal proteins and defining the entire peroxisomal proteome of Arabidopsis
      and agronomically important crop plants. PredPlantPTS1 is freely accessible at
      ppp.gobics.de.

PMID- 22969784
TI  - The Effects of Inorganic Nitrogen form and CO(2) Concentration on Wheat Yield and
      Nutrient Accumulation and Distribution.
AB  - Inorganic N is available to plants from the soil as ammonium [Formula: see text]
      and nitrate [Formula: see text]. We studied how wheat grown hydroponically to
      senescence in controlled environmental chambers is affected by N form ([Formula:
      see text] vs. [Formula: see text]) and CO(2) concentration ("subambient,"
      "ambient," and "elevated") in terms of biomass, yield, and nutrient accumulation
      and partitioning. Wheat supplied with [Formula: see text] as a sole N source had
      the strongest response to CO(2) concentration. Plants exposed to subambient and
      ambient CO(2) concentrations typically had the greatest biomass and nutrient
      accumulation under both N forms. In general [Formula: see text]-supplied plants
      had higher concentrations of total N, P, K, S, Ca, Zn, Fe, and Cu, while
      [Formula: see text]-supplied plants had higher concentrations of Mg, B, Mn, and
      [Formula: see text][Formula: see text]-supplied plants contained amounts of
      phytate similar to [Formula: see text]-supplied plants but had higher
      bioavailable Zn, which could have consequences for human health. [Formula: see
      text]-supplied plants allocated more nutrients and biomass to aboveground tissues
      whereas [Formula: see text]-supplied plants allocated more nutrients to the
      roots. The two inorganic nitrogen forms influenced plant growth and nutrient
      status so distinctly that they should be treated as separate nutrients. Moreover,
      plant growth and nutrient status varied in a non-linear manner with atmospheric
      CO(2) concentration.

PMID- 22969785
TI  - Environmental effects on allergen levels in commercially grown non-genetically
      modified soybeans: assessing variation across north america.
AB  - Soybean (Glycinemax) is a hugely valuable soft commodity that generates tens of
      billions of dollars annually. This value is due in part to the balanced
      composition of the seed which is roughly 1:2:2 oil, starch, and protein by
      weight. In turn, the seeds have many uses with various derivatives appearing
      broadly in processed food products. As is true with many edible seeds, soybeans
      contain proteins that are anti-nutritional factors and allergens. Soybean, along
      with milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, and wheat,
      elicit a majority of food allergy reactions in the United States. Soybean seed
      composition can be affected by breeding, and environmental conditions (e.g.,
      temperature, moisture, insect/pathogen load, and/or soil nutrient levels). The
      objective of this study was to evaluate the influence of genotype and environment
      on allergen and anti-nutritional proteins in soybean. To address genetic and
      environmental effects, four varieties of non-GM soybeans were grown in six
      geographically distinct regions of North America (Georgia, Iowa, Kansas,
      Nebraska, Ontario, and Pennsylvania). Absolute quantification of proteins by mass
      spectrometry can be achieved with a technique called multiple reaction monitoring
      (MRM), during which signals from an endogenous protein are compared to those from
      a synthetic heavy-labeled internal standard. Using MRM, eight allergens were
      absolutely quantified for each variety in each environment. Statistical analyses
      show that for most allergens, the effects of environment far outweigh the
      differences between varieties brought about by breeding.

PMID- 22969786
TI  - Syntenic gene analysis between Brassica rapa and other Brassicaceae species.
AB  - Chromosomal synteny analysis is important in genome comparison to reveal genomic
      evolution of related species. Shared synteny describes genomic fragments from
      different species that originated from an identical ancestor. Syntenic genes are
      orthologs located in these syntenic fragments, so they often share similar
      functions. Syntenic gene analysis is very important in Brassicaceae species to
      share gene annotations and investigate genome evolution. Here we designed and
      developed a direct and efficient tool, SynOrths, to identify pairwise syntenic
      genes between genomes of Brassicaceae species. SynOrths determines whether two
      genes are a conserved syntenic pair based not only on their sequence similarity,
      but also by the support of homologous flanking genes. Syntenic genes between
      Arabidopsis thaliana and Brassica rapa, Arabidopsis lyrata and B. rapa, and
      Thellungiella parvula and B. rapa were then identified using SynOrths. The
      occurrence of genome triplication in B. rapa was clearly observed, many genes
      that were evenly distributed in the genomes of A. thaliana, A. lyrata, and T.
      parvula had three syntenic copies in B. rapa. Additionally, there were many B.
      rapa genes that had no syntenic orthologs in A. thaliana, but some of these had
      syntenic orthologs in A. lyrata or T. parvula. Only 5,851 genes in B. rapa had no
      syntenic counterparts in any of the other three species. These 5,851 genes could
      have originated after B. rapa diverged from these species. A tool for syntenic
      gene analysis between species of Brassicaceae was developed, SynOrths, which
      could be used to accurately identify syntenic genes in differentiated but closely
      related genomes. With this tool, we identified syntenic gene sets between B. rapa
      and each of A. thaliana, A. lyrata, T. parvula. Syntenic gene analysis is
      important for not only the gene annotation of newly sequenced Brassicaceae
      genomes by bridging them to model plant A. thaliana, but also the study of genome
      evolution in these species.

PMID- 22969787
TI  - Symposia on plant (protein) phosphorylation.

PMID- 22969788
TI  - Coming to terms with complexity: limits to a reductionist view of aging.

PMID- 22969789
TI  - Detection of expression quantitative trait Loci in complex mouse crosses: impact
      and alleviation of data quality and complex population substructure.
AB  - Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased
      resolution for quantitative trait loci detection. However, increased genetic
      complexity challenges detection methods, with discordant results due to low data
      quality or complex genetic architecture. We quantified the impact of theses
      factors across three mouse crosses and two different detection methods,
      identifying procedures that greatly improve detection quality. Importantly, HS
      populations have complex genetic architectures not fully captured by the whole
      genome kinship matrix, calling for incorporating chromosome specific relatedness
      information. We analyze three increasingly complex crosses, using gene expression
      levels as quantitative traits. The three crosses were an F(2) intercross, a HS
      formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the
      eight lines found in the collaborative cross. Brain (striatum) gene expression
      and genotype data were obtained using the Illumina platform. We found large
      disparities between methods, with concordance varying as genetic complexity
      increased; this problem was more acute for probes with distant regulatory
      elements (trans). A suite of data filtering steps resulted in substantial
      increases in reproducibility. Genetic relatedness between samples generated
      overabundance of detected eQTLs; an adjustment procedure that includes the
      kinship matrix attenuates this problem. However, we find that relatedness between
      individuals is not evenly distributed across the genome; information from
      distinct chromosomes results in relatedness structure different from the whole
      genome kinship matrix. Shared polymorphisms from distinct chromosomes
      collectively affect expression levels, confounding eQTL detection. We suggest
      that considering chromosome specific relatedness can result in improved eQTL
      detection.

PMID- 22969790
TI  - Big (sequencing) future of non-coding RNA research for the understanding of
      cocaine.

PMID- 22969791
TI  - Systematic underestimation of the age of selected alleles.
AB  - A common interpretation of genome-wide selection scans is that the dispersal of
      anatomically modern humans out of Africa and into diverse environments led to a
      number of genetic adaptations. If so, patterns of polymorphism from non-African
      individuals should show the signature of adaptations dating to 40,000-100,000
      Kya, coinciding with the main exodus from Africa. However, scans of polymorphism
      data from a few populations have yielded conflicting results about the chronology
      of local, population-specific adaptations. In particular, a number of papers
      report very recent ages for selected alleles in humans, which postdate the
      development of agriculture 10 Kya, and suggest that adaptive differences among
      human populations are much more recent. I present an analysis of simulations
      suggesting a downward bias in methods commonly used to estimate the age of
      selected alleles. These findings indicate that an estimate of a time to the most
      recent common ancestor (tMRCA) obtained using standard methods (used as a proxy
      for the age of an allele) of less than 10 Kya is consistent with an allele that
      actually became selected before the onset of agriculture and potentially as early
      as 50 Kya. These findings suggest that the genomic scans for selection may be
      consistent with selective pressures tied to the Out of Africa expansion of modern
      human populations.

PMID- 22969792
TI  - Evolution and complexity of micro RNA in the human brain.

PMID- 22969793
TI  - Infant development in family context: call for a genetically informed approach.
AB  - We call for a genetically informed approach in the examination of infant social
      and emotional development in family context. We recommend that scholars
      conceptualize family functioning as occurring on three unique levels: the parent
      child dyad, the inter-parental dyad, and whole family functioning. Although
      advances in the area of understanding genetic variation in infants as a potential
      moderator of the influence of parent-child dyadic functioning have been made over
      the past decade, it is time to widen this inquiry to consider genetic variation
      in infants as a potential moderator of the influence of inter-parental dyadic and
      whole family functioning as well. A critical review of the literature also calls
      for additional examination of genetic variation in infants as a moderator of
      positive contextual influences, the integration of unique temperament variables
      with studies of infant genotype, consideration of the role of the gene
      environment correlation, and epigenetic effects. Furthermore, we call for the
      application of genetically-informed research methods to these questions.
      Expanding knowledge in this area has the potential to refine treatment and
      prevention efforts aimed at promoting infant social and emotional development.

PMID- 22969794
TI  - Regulation of chromatin structure by poly(ADP-ribosyl)ation.
AB  - The interaction of DNA with proteins in the context of chromatin has to be
      tightly regulated to achieve so different tasks as packaging, transcription,
      replication and repair. The very rapid and transient post-translational
      modification of proteins by poly(ADP-ribose) has been shown to take part in all
      four. Originally identified as immediate cellular answer to a variety of
      genotoxic stresses, already early data indicated the ability of this highly
      charged nucleic acid-like polymer to modulate nucleosome structure, the basic
      unit of chromatin. At the same time the enzyme responsible for synthesizing
      poly(ADP-ribose), the zinc-finger protein poly(ADP-ribose) polymerase-1 (PARP1),
      was shown to control transcription initiation as basic factor TFIIC within the
      RNA-polymerase II machinery. Later research focused more on PARP-mediated
      regulation of DNA repair and cell death, but in the last few years, transcription
      as well as chromatin modulation has re-appeared on the scene. This review will
      discuss the impact of PARP1 on transcription and transcription factors, its
      implication in chromatin remodeling for DNA repair and probably also replication,
      and its role in controlling epigenetic events such as DNA methylation and the
      functionality of the insulator protein CCCTC-binding factor.

PMID- 22969797
TI  - Lessons learned from implementing the patient-centered medical home.
AB  - The Patient-Centered Medical Home (PCMH) is a primary care model that provides
      coordinated and comprehensive care to patients to improve health outcomes. This
      paper addresses practical issues that arise when transitioning a traditional
      primary care practice into a PCMH recognized by the National Committee for
      Quality Assurance (NCQA). Individual organizations' experiences with this
      transition were gathered at a PCMH workshop in Alexandria, Virginia in June 2010.
      An analysis of their experiences has been used along with a literature review to
      reveal common challenges that must be addressed in ways that are responsive to
      the practice and patients' needs. These are: NCQA guidance, promoting provider
      buy-in, leveraging electronic medical records, changing office culture, and
      realigning workspace in the practice to accommodate services needed to carry out
      the intent of PCMH. The NCQA provides a set of standards for implementing the
      PCMH model, but these standards lack many specifics that will be relied on in
      location situations. While many researchers and providers have made critiques, we
      see this vagueness as allowing for greater flexibility in how a practice
      implements PCMH.

PMID- 22969795
TI  - Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and
      the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.
AB  - Psychological stress, an evolutionary adaptation to the fight-or-flight response,
      triggers a number of physiological responses that can be deleterious under some
      circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA)
      axis and the sympathetic nervous system. Elements derived from those systems
      (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system
      and possible disease states. Skin provides a first line of defense against many
      environmental insults. A number of investigations have indicated that the skin is
      especially sensitive to psychological stress, and experimental evidence shows
      that the cutaneous innate and adaptive immune systems are affected by stressors.
      For example, psychological stress has been shown to reduce recovery time of the
      stratum corneum barrier after its removal (innate immunity) and alters antigen
      presentation by epidermal Langerhans cells (adaptive immunity). Moreover,
      psychological stress may trigger or exacerbate immune mediated dermatological
      disorders. Understanding how the activity of the psyche-nervous -immune system
      axis impinges on skin diseases may facilitate coordinated treatment strategies
      between dermatologists and psychiatrists. Herein, we will review the roles of the
      HPA axis and the sympathetic nervous system on the cutaneous immune response. We
      will selectively highlight how the interplay between psychological stress and the
      immune system affects atopic dermatitis and psoriasis.

PMID- 22969796
TI  - Fecal molecular markers for colorectal cancer screening.
AB  - Despite multiple screening techniques, including colonoscopy, flexible
      sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal
      cancer remains a leading cause of death. As these techniques improve, their
      sensitivity to detect malignant lesions is increasing; however, detection of
      precursor lesions remains problematic and has generated a lack of general
      acceptance for their widespread usage. Early detection by an accurate,
      noninvasive, cost-effective, simple-to-use screening technique is central to
      decreasing the incidence and mortality of this disease. Recent advances in the
      development of molecular markers in faecal specimens are encouraging for its use
      as a screening tool. Genetic mutations and epigenetic alterations that result
      from the carcinogenetic process can be detected by coprocytobiology in the
      colonocytes exfoliated from the lesion into the fecal matter. These markers have
      shown promising sensitivity and specificity in the detection of both malignant
      and premalignant lesions and are gaining popularity as a noninvasive technique
      that is representative of the entire colon. In this paper, we summarize the
      genetic and epigenetic fecal molecular markers that have been identified as
      potential targets in the screening of colorectal cancer.

PMID- 22969798
TI  - A modeled analysis of telehealth methods for treating pressure ulcers after
      spinal cord injury.
AB  - Home telehealth can improve clinical outcomes for conditions that are common
      among patients with spinal cord injury (SCI). However, little is known about the
      costs and potential savings associated with its use. We developed clinical
      scenarios that describe common situations in treatment or prevention of pressure
      ulcers. We calculated the cost implications of using telehealth for each scenario
      and under a range of reasonable assumptions. Data were gathered primarily from US
      Department of Veterans Affairs (VA) administrative records. For each scenario and
      treatment method, we multiplied probabilities, frequencies, and costs to
      determine the expected cost over the entire treatment period. We generated low-,
      medium-, and high-cost estimates based on reasonable ranges of costs and
      probabilities. Telehealth care was less expensive than standard care when low
      cost technology was used but often more expensive when high-cost, interactive
      devices were installed in the patient's home. Increased utilization of telehealth
      technology (particularly among rural veterans with SCI) could reduce the
      incidence of stage III and stage IV ulcers, thereby improving veterans' health
      and quality of care without increasing costs. Future prospective studies of our
      present scenarios using patients with various healthcare challenges are
      recommended.

PMID- 22969799
TI  - Measurement of salivary resistin level in patients with type 2 diabetes.
AB  - Serum resistin was initially hypothesized as a link between obesity and insulin
      resistance in mice. The latest evidence suggests that serum resistin is
      proinflammatory cytokines. Inflammation plays a key role in the pathogenesis of
      type 2 diabetes mellitus (T2DM). Many reports have previously identified changed
      serum resistin levels in patients with T2DM, but little is known of the levels of
      resistin in saliva. In our study, saliva and serum samples were collected from 38
      patients with newly diagnosed T2DM at each time point of OGTT and 35 nondiabetic
      controls at fasting state. Resistin concentrations were measured using ELISA. We
      have demonstrated the presence of resistin in saliva of T2DM and nondiabetic
      subjects. Saliva resistin levels of T2DM are significantly higher than those of
      nondiabetic controls. Resistin levels in saliva are not affected by eating
      activity and correlated with serum resistin levels at any time points of OGTT. A
      positive correlation of serum and salivary resistin with BMI and HOMA-IR existed
      in T2DM. Measurement of resistin in saliva is a simple, noninvasive and may be an
      acceptable alternative to blood sampling for
      evaluatinginflammation/obesity/insulin resistance state.

PMID- 22969800
TI  - Pathogenesis and new therapeutic targets of ovarian cancer.

PMID- 22969801
TI  - Predictors of immunosuppressive regulatory T lymphocytes in healthy women.
AB  - Immunosuppressive regulatory T (Treg) cells play an important role in antitumor
      immunity, self-tolerance, transplantation tolerance, and attenuation of allergic
      response. Higher proportion of Treg cells has been observed in peripheral blood
      of cancer cases compared to controls. Little is known about potential
      epidemiological predictors of Treg cell levels in healthy individuals. We
      conducted a cross-sectional study including 75 healthy women, between 20 and 80
      years of age, who participated in the Data Bank and BioRepository (DBBR) program
      at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood
      levels of CD4(+)CD25(+)FOXP3(+) Treg cells were measured using flow cytometric
      analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test,
      Kruskal-Wallis test, and linear regression. Age, smoking, medications for
      treatment of osteoporosis, postmenopausal status, body mass index (BMI), and
      hormone replacement therapy (HRT) were found to be significant positive
      predictors of Treg cell levels in peripheral blood (P <= 0.05). Higher education,
      exercise, age at first birth, oral contraceptives, and use of Ibuprofen were
      found be significant (P < 0.05) negative predictors of Treg levels. Thus, various
      epidemiological risk factors might explain interindividual variation in immune
      response to pathological conditions, including cancer.

PMID- 22969802
TI  - Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS
      Study.
AB  - Background. Metabolic syndrome has been linked to an increased cancer risk, but
      the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed
      to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum
      levels of lipid components. Methods. From the Swedish Apolipoprotein Mortality
      Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with
      baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose
      of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL),
      apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox
      proportional hazards regression was used to assess glucose and lipid components
      in relation to oesophageal, stomach, colon, and rectal cancer risk. Results. An
      increased risk of oesophageal cancer was observed in persons with high TG (e.g.
      HR: 2.29 (95% CI: 1.42-3.68) for the 4th quartile compared to the 1st) and low
      LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoA-I ratio. High
      glucose and TG were linked with an increased colon cancer risk, while high TC
      levels were associated with an increased rectal cancer risk. Conclusion. The
      persistent link between TC and rectal cancer risk as well as between TG and
      oesophageal and colon cancer risk in normoglycaemic individuals may imply their
      substantiality in gastrointestinal carcinogenesis.

PMID- 22969803
TI  - Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding
      Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients:
      An Observational Cohort Study Based on SEER-Medicare.
AB  - Rituximab improves survival in follicular lymphoma (FL), but is considerably more
      expensive than conventional chemotherapy. We estimated the total direct medical
      costs, cumulative survival, and cost-effectiveness of adding rituximab to first
      line chemotherapy for FL, based on a single source of data representing routine
      practice in the elderly. Using surveillance, epidemiology, and end results (SEER)
      registry data plus Medicare claims, we identified 1,117 FL patients who received
      first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and
      prednisone (P)) or CVP +/- rituximab. Multivariate regression was used to
      estimate adjusted cumulative cost and survival differences between the two groups
      over four years after beginning treatment. The median age was 73 years (minimum
      66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding
      rituximab to first-line chemotherapy was associated with higher adjusted
      incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and
      longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four
      years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531
      296,337) per life-year gained. In routine clinical practice, adding rituximab to
      first-line chemotherapy for elderly patients with FL results in higher direct
      medical costs to Medicare and longer cumulative survival after four years.

PMID- 22969804
TI  - A Comparative Evaluation for Biologic Width following Surgical Crown Lengthening
      Using Gingivectomy and Ostectomy Procedure.
AB  - Surgical crown lengthening has been proposed as a means of facilitating
      restorative procedures and preventing injuries in teeth with structurally
      inadequate clinical crown or exposing tooth structure in the presence of deep,
      subgingival pathologies which may hamper the access for proper restorative
      measures. Histological studies utilizing animal models have shown that
      postoperative crestal resorption allowed reestablishment of the biologic width.
      However, very little has been done in humans. Aims. The purpose of the study was
      to evaluate the potential changes in the periodontal tissues, particularly the
      biologic width, following surgical crown lengthening by two surgical procedures
      before and after crown placement. Methods and Material. Twenty (20) patients who
      needed surgical crown lengthening to gain retention necessary for prosthetic
      treatment and/or to access caries, tooth fracture, or previous prosthetic margins
      entered the study. The following parameters were obtained from line angles of
      treated teeth (teeth requiring surgical crown lengthening) and adjacent sites:
      Plaque and Gingival Indices (PI) & (GI), Position of Gingival Margin from
      reference Stent (PGMRS), Probing depth (PD), and Biologic Width (BW). Statistical
      Analysis Used. Student "t" Test. Results. Initial baseline values of biologic
      width were 2.55 mm (Gingivectomy procedure B1 Group) and 1.95 mm (Ostectomy
      procedure B2 Group) and after surgical procedure the values were 1.15 mm and 1.25
      mm. Conclusions. Within the limitations of the study the biologic width, at
      treated sites, was re-established to its original vertical dimension by 3 months.
      Ostectomy with apically positioned flap can be considered as a more effective
      procedure than Gingivectomy for Surgical Crown Lengthening.

PMID- 22969805
TI  - Tricho-dento-osseous syndrome: diagnosis and dental management.
AB  - Tricho-dento-osseous (TDO) syndrome is a rare, autosomal dominant disorder
      principally characterised by curly hair at infancy, severe enamel
      hypomineralization and hypoplasia and taurodontism of teeth, sclerotic bone, and
      other defects. Diagnostic criteria are based on the generalized enamel defects,
      severe taurodontism especially of the mandibular first permanent molars, an
      autosomal dominant mode of inheritance, and at least one of the other features
      (i.e., nail defects, bone sclerosis, and curly, kinky or wavy hair present at a
      young age that may straighten out later). Confusion with amelogenesis imperfecta
      is common; however, taurodontism is not a constant feature of any of the types of
      amelogenesis imperfecta. Management of TDO requires a team approach, proper
      documentation, and a long-term treatment and follow-up plan. The aim of treatment
      is to prevent problems such as sensitivity, caries, dental abscesses, and loss of
      occlusal vertical dimension through attrition of hypoplastic tooth structure.
      Another aim is to restore function of the dentition and enhance the esthetics and
      self-esteem of the patient. This paper proposes treatment approaches that include
      preventive, restorative, endodontic, prosthetic, and surgical options to
      management. In addition, it sheds light on the difficulties faced during dental
      treatment of such cases.

PMID- 22969806
TI  - Physicochemical Characterization and In Vivo Evaluation of Amorphous and
      Partially Crystalline Calcium Phosphate Coatings Fabricated on Ti-6Al-4V Implants
      by the Plasma Spray Method.
AB  - Objective. To characterize the topographic and chemical properties of 2
      bioceramic coated plateau root form implant surfaces and evaluate their
      histomorphometric differences at 6 and 12 weeks in vivo. Methods. Plasma sprayed
      hydroxyapatite (PSHA) and amorphous calcium phosphate (ACP) surfaces were
      characterized by scanning electron microscopy (SEM), interferometry (IFM), X-ray
      diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). Implants
      were placed in the radius epiphysis, and the right limb of dogs provided implants
      that remained for 6 weeks, and the left limb provided implants that remained 12
      weeks in vivo. Thin sections were prepared for bone-to-implant contact (BIC) and
      bone-area-fraction occupancy (BAFO) measurements (evaluated by Friedman analysis
      P < 0.05). Results. Significantly, higher S(a) (P < 0.03) and S(q) (P < 0.02)
      were observed for ACP relative to PSHA. Chemical analysis revealed significantly
      higher HA, calcium phosphate, and calcium pyrophosphate for the PSHA surface. BIC
      and BAFO measurements showed no differences between surfaces. Lamellar bone
      formation in close contact with implant surfaces and within the healing chambers
      was observed for both groups. Conclusion. Given topographical and chemical
      differences between PSHA and ACP surfaces, bone morphology and histomorphometric
      evaluated parameters showed that both surfaces were osseoconductive in plateau
      root form implants.

PMID- 22969807
TI  - Posterior semicircular canal benign paroxysmal positional vertigo presenting with
      torsional downbeating nystagmus: an apogeotropic variant.
AB  - The aim of this study is to verify the hypothesis that free-floating particles
      could sometimes localize into the distal portion of the non ampullary arm of the
      posterior semicircular canal (PSC) so that assuming the Dix-Hallpike's positions,
      the clot could move towards the ampulla eliciting a inhibitory torsional-down
      beating paroxysmal positional nystagmus (PPNy), instead of typical excitatory
      torsional-up beating PPNy. Among 45 patients with vestibular signs suggesting
      anterior semicircular canal paroxysmal positional vertigo (PPV), collected from
      February 2003 to August 2006, we detected a group of 6 subjects whose clinical
      findings showed a singular behaviour during follow-up. At the first check-up, all
      patients were submitted to different types of physical manoeuvres for ASC
      canalolithiasis. Patients were controlled during the same session and after one
      week. When we found that nystagmus was qualitatively changed we adopted the
      appropriate physical therapies for that sign. At a next check-up, after having
      performed some physical therapies, all patients had a typical PSC PPNy of the
      opposite side, with respect to that of the ASC initially diagnosed. Basing on
      these observations we conclude that PSC PPV, similarly to lateral semicircular
      canal PPV, could manifests in a apogeotropic variant.

PMID- 22969809
TI  - Case report of a prostatic abscess with a review of the literature.
AB  - A middle age male with type 2 diabetes mellitus presented with urinary symptoms.
      Blood and urine cultures were consistent with Methicillin Resistant Staphylcoccal
      Aureus (MRSA). A computed tomography demonstrated mutiple prostatic
      microabscessess. No other hematogenous source was identified. Transurethral
      prostatic drainage and intravenous Vancomycin followed by oral doxcycline led to
      clinical success for this likely Community acquired case of MRSA (CA-MRSA). We
      discuss our case report and discuss the current literature on the trends,
      causation, diagnosis and treatment of MRSA induced prostatic abscess.

PMID- 22969808
TI  - An unusual cause of a pain in the neck: pseudoaneurysm from tuberculous
      lymphadenitis.
AB  - A pseudoaneurysm is a haematoma which is surrounded by connective tissue and
      communicates with the lumen of a ruptured blood vessel. It has no true defined
      capsule. We describe a case of tuberculous pseudoaneurysm. This is a rare
      complication of tuberculosis. The clinical presentation of these lesions is
      highly variable. Definitive diagnosis should consist of contrast-enhanced CT and
      arteriography. Treatment should include repair of the arterial wall by surgery,
      endovascular stent-graft insertion, or embolization followed by a full course of
      antituberculous chemotherapy. Our case is highly unusual in that the
      pseudoaneurysm arose from the subclavian vasculature in a patient with
      extrapulmonary tuberculosis only.

PMID- 22969810
TI  - Coronary subclavian steal syndrome causing acute myocardial infarction in a
      patient undergoing coronary-artery bypass grafting.
AB  - Coronary subclavian steal syndrome with retrograde blood flow in the left
      internal mammary-coronary bypass graft is a rare but severe complication of
      cardiac surgery. The authors present a case of a 68-year-old man after coronary
      artery bypass grafting using an internal mammary artery. He had been suffering
      from angina pectoris for the last several years before surgery. The patient was
      resuscitated at home by emergency medical service because of primary ventricular
      fibrillation due to an acute myocardial infarction 5 years after surgery. An
      occlusion of the left subclavian artery with the retrograde blood flow in the
      left internal mammary coronary bypass was found. This could have been the cause
      of insufficiency in coronary blood flow and ischemia of the myocardial muscle.
      The subclavian artery occlusion was successfully treated with percutaneous
      transluminal angioplasty and implantation of 2 stents. The patient remained free
      of any symptoms 2 years after this procedure.

PMID- 22969811
TI  - Basic biology and clinical application of multipotent mesenchymal stromal cells:
      from bench to bedside.

PMID- 22969813
TI  - Expression of SIRT1 and DBC1 in Developing and Adult Retinas.
AB  - Sirtuin 1 (SIRT1) is a deacetylase that can regulate various biological processes
      via repression of transcription. Its activity has been linked to the
      differentiation of neural progenitor cells, although little is known about its
      function during retinal development. The study described herein was undertaken to
      evaluate the expression of SIRT1 and its innate inhibitor, DBC1, in retinal
      tissues and progenitor cells. We found both SIRT1 and DBC1 to be widely expressed
      in mouse and human retinas, with subtle differences in subcellular distribution
      of each protein. We further demonstrate that nuclear-localized SIRT1 is only seen
      in human-derived retinal progenitor cells and not in adult retinas, suggesting
      that this nuclear localization may be important in retinal development. Moreover,
      we observed cytoplasmic DBC1 in a subset of progenitor cells as well as in mature
      ganglion cells, indicating that the progenitor cell subset, which was comprised
      predominantly of small cells, may represent a population of ganglion cell
      precursors. Collectively, the data presented in this study provide support for
      SIRT1 and DBC1 as regulators of retinal development and normal retinal
      physiology.

PMID- 22969812
TI  - Prospective in vitro models of channelopathies and cardiomyopathies.
AB  - An in vitro heart disease model is a promising model used for identifying the
      genes responsible for the disease, evaluating the effects of drugs, and
      regenerative medicine. We were interested in disease models using a patient
      induced pluripotent stem (iPS) cell-derived cardiomyocytes because of their
      similarity to a patient's tissues. However, as these studies have just begun, we
      would like to review the literature in this and other related fields and discuss
      the path for future models of molecular biology that can help to diagnose and
      cure diseases, and its involvement in regenerative medicine. The heterogeneity of
      iPS cells and/or differentiated cardiomyocytes has been recognized as a problem.
      An in vitro heart disease model should be evaluated using molecular biological
      analyses, such as mRNA and micro-RNA expression profiles and proteomic analysis.

PMID- 22969814
TI  - Mortality Related to Chagas Disease and HIV/AIDS Coinfection in Brazil.
AB  - Chagas disease in patients with HIV infection represents a potentially serious
      event with high case fatality rates. This study describes epidemiological and
      clinical aspects of deaths related to Chagas disease and HIV/AIDS coinfection in
      Brazil, 1999-2007. We performed a descriptive study based on mortality data from
      the nationwide Mortality Information System. Of a total of about 9 million
      deaths, Chagas disease and HIV/AIDS were mentioned in the same death certificate
      in 74 cases. AIDS was an underlying cause in 77.0% (57) and Chagas disease in
      17.6% (13). Males (51.4%), white skin color (50%), age group 40-49 years (29.7%),
      and residents in the Southeast region (75.7%) were most common. Mean age at death
      was significantly lower in the coinfected (47.1 years [SD +/- 14.6]), as compared
      to Chagas disease deaths (64.1 years [SD +/- 14.7], P < 0.001). Considering the
      lack of data on morbidity related to Chagas disease and AIDS coinfection, the use
      of mortality data may be an appropriate sentinel approach to monitor the
      occurrence of this association. Due to the epidemiological transition in Brazil,
      chronic Chagas disease and HIV/AIDS coinfection will be further complicated and
      require the development of evidence-based preventive control measures.

PMID- 22969815
TI  - Pilot study on the impact of biogas as a fuel source on respiratory health of
      women on rural Kenyan smallholder dairy farms.
AB  - Biomass burning in indoor environments has been highlighted as a major cause of
      respiratory morbidity for women and children in low-income countries. Inexpensive
      technological innovations which reduce such exposures are needed. This study
      evaluated the impact of low tech compost digesters, which generate biogas for
      cooking, versus traditional fuel sources on the respiratory health of nonsmoking
      Kenyan farmwomen. Women from 31 farms with biogas digesters were compared to age
      matched women from 31 biomass-reliant farms, in June 2010. Only 43% of the biogas
      group reported any breathing problems, compared to 71% in the referent group (P =
      0.03). Referent women self-reported higher rates of shortness of breath (52%
      versus 30%), difficulty breathing (42% versus 23%), and chest pain while
      breathing (35% versus 17%) during the last 6 months (P = 0.09 to 0.12) compared
      to biogas women. Biogas women demonstrated slightly better spirometry results but
      differences were not statistically significant, likely due to limited latency
      between biogas digester installation and spirometry testing. Most biogas women
      reported improved personal respiratory health (87%) and improved children's
      health (72%) since biogas digester installation. These findings suggest that
      using biogas in cookhouses improves respiratory symptoms but long-term impacts on
      lung function are unclear.

PMID- 22969817
TI  - Perinatal programming of childhood asthma.

PMID- 22969816
TI  - Hematopoietic stem cell transplantation for systemic lupus erythematosus.
AB  - Two streams of research are at the origin of the utilization of hematopoietic
      stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The
      allogeneic approach came from experimental studies on lupus mice, besides
      clinical results in coincidental diseases. The autologous procedure was
      encouraged by researches on experimental neurological and rheumatic disorders. At
      present the number of allogeneic HSCT performed for human SADs can be estimated
      to not over 100 patients, and the results are not greatly encouraging,
      considering the significant transplant-related mortality (TRM) and the occasional
      development of a new autoimmune disorder and/or relapses notwithstanding full
      donor chimerism. Autologous HSCT for refractory SLE has become a major target.
      Severe cases have been salvaged, TRM is low and diminishing, and prolonged
      clinical remissions are obtainable. Two types of immune resetting have been
      established, "re-education" and regulatory T cell (Tregs) normalization.
      Allogeneic HSCT for SLE seems best indicated for patients with disease
      complicated by an oncohematologic malignancy. Autologous HSCT is a powerful
      salvage therapy for otherwise intractable SLE. The duration of remission in
      uncertain, but a favorable response to previously inactive treatments is a
      generally constant feature. The comparison with new biological agents, or the
      combination of both, are to be ascertained.

PMID- 22969818
TI  - Parasite-specific IL-17-type cytokine responses and soluble IL-17 receptor levels
      in Alveolar Echinococcosis patients.
AB  - Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis,
      is a severe helminth infection of man, where unrestricted parasite growth will
      ultimately result in organ failure and fatality. The tissue-infiltrative growth
      of the larval metacestode and the limited efficacy of available drugs complicate
      successful intervention in AE; patients often need life-long medication, and if
      possible, surgical resection of affected tissues and organs. Resistance to AE has
      been reported, but the determinants which confer protection are not known. ln
      this study, we analyzed in patients at distinct stages of Alveolar
      Echirococcosis, that is cured, stable and progressive AE, as well as in infection
      free controls, the cellular production and plasma levels of pro-inflammatory
      cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA)
      and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were
      observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly,
      the cellular production of lL-17F and slL-L7RA in response to E. multilocularis
      antigens was low in AE patients, while levels of slL-17RB were highly enhanced.
      These observations suggest immune-modulating properties of E. multitocularis on
      lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate
      the tissue infiltrative growth of the parasite and its persistence in the human
      host.

PMID- 22969820
TI  - Development of a biocrystallisation assay for examining effects of homeopathic
      preparations using cress seedlings.
AB  - A major challenge in basic research into homeopathic potentisation is to develop
      bioassays that yield consistent results. We evaluated the potential of a seedling
      biocrystallisation method. Cress seeds (Lepidium sativum L.) germinated and grew
      for 4 days  in vitro in Stannum metallicum 30x or water 30x in blinded and
      randomized assignment. 15 experiments were performed at two laboratories. CuCl(2)
      biocrystallisation of seedlings extracted in the homeopathic preparations was
      performed on circular glass plates. Resulting biocrystallograms were analysed by
      computerized textural image analysis. All texture analysis variables analysed
      yielded significant results for the homeopathic treatment; thus the texture of
      the biocrystallograms of homeopathically treated cress exhibited specific
      characteristics. Two texture analysis variables yielded differences between the
      internal replicates, most probably due to a processing order effect. There were
      only minor differences between the results of the two laboratories. The
      biocrystallisation method seems to be a promising complementary outcome measure
      for plant bioassays investigating effects of homeopathic preparations.

PMID- 22969819
TI  - Tolerogenic versus inflammatory activity of peripheral blood monocytes and
      dendritic cells subpopulations in systemic lupus erythematosus.
AB  - Abnormalities in monocytes and in peripheral blood dendritic cells (DC) subsets
      have been reported in systemic lupus erythematosus (SLE). We aim to clarify the
      tolerogenic or inflammatory role of these cells based on ICOSL or IFN-alpha and
      chemokine mRNA expression, respectively, after cell purification. The study
      included 18 SLE patients with active disease (ASLE), 25 with inactive disease
      (ISLE), and 30 healthy controls (HG). In purified plasmacytoid DC (pDC) was
      observed a lower ICOSL mRNA expression in ASLE and an increase in ISLE;
      similarly, a lower ICOSL mRNA expression in monocytes of ALSE patients was found.
      However, a higher ICOSL mRNA expression was observed in ASLE compared to HG in
      myeloid DCs. Interestingly, clinical parameters seem to be related with ICOSL
      mRNA expression. Regarding the inflammatory activity it was observed in purified
      monocytes and CD14(-/low) CD16(+) DCs an increase of CCL2, CXCL9, and CXCL10 mRNA
      expression in ASLE compared to HG. In myeloid DC no differences were observed
      regarding chemokines, and IFN-alpha mRNA expression. In pDC, a higher IFN-alpha
      mRNA expression was observed in ASLE. Deviations in ICOSL, chemokine, and IFN
      alpha mRNA expression in peripheral blood monocytes and dendritic cells
      subpopulations in SLE appear to be related to disease activity.

PMID- 22969821
TI  - Evaluation of Effects of Chinese Prescription Kangen-karyu on Diabetes-Induced
      Alterations such as Oxidative Stress and Apoptosis in the Liver of Type 2
      Diabetic db/db Mice.
AB  - The present study was conducted to examine whether Kangen-karyu has an
      ameliorative effect on diabetes-induced alterations such as oxidative stress and
      apoptosis in the liver of type 2 diabetic db/db mice. Kangen-karyu (100 or 200
      mg/kg body weight/day, p.o.) was administered every day for 18 weeks to db/db
      mice and its effect was compared with vehicle-treated db/db and m/m mice. The
      administration of Kangen-karyu decreased the elevated serum glucose and leptin
      concentrations in db/db mice, and reduced the increased oxidative biomarkers
      including the generation of reactive oxygen species and lipid peroxidation in the
      liver. The db/db mice exhibited the upregulation of nicotinamide adenine
      dinucleotide phosphate oxidase subunits, NF-E2-related factor 2, heme oxygenase
      1, nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase
      levels in the liver; however, Kangen-karyu treatment significantly reduced those
      expressions. Moreover, the augmented expressions of apoptosis-related proteins,
      Bax, cytochrome c, c-Jun N-terminal kinase (JNK), phosphor-JNK, AP-1, and caspase
      3, were downregulated by Kangen-karyu administration. Hematoxylin-eosin staining
      showed that the increased hepatocellular damage in the liver of db/db mice
      improved by Kangen-karyu administration. Our findings support the therapeutic
      evidence for Kangen-karyu ameliorating the development of diabetic hepatic
      complications via regulating oxidative stress and apoptosis.

PMID- 22969822
TI  - Synergistic Cytotoxic Effects of Ganoderma lucidum and Bacillus Calmette Guerin
      on Premalignant Urothelial HUC-PC Cells and Its Regulation on Proinflammatory
      Cytokine Secretion.
AB  - Bacillus Calmette-Guerin (BCG) is conventionally used as an adjuvant
      immunotherapy to reduce the recurrence of bladder cancer. To address the issues
      of efficacy and safety, an ethanol extract of Ganoderma lucidum (GLe) was
      evaluated for its interaction with BCG. In a model of premalignant human
      uroepithelial cells (HUC-PC), GLe exerted immediate cytotoxic effects while BCG
      showed a delayed response, given that both were immunological active in inducing
      the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1
      (MCP-1). Synergistic cytotoxic effects were observed when cells were either
      coincubated with both drugs or firstly preincubated with GLe. Synergism between
      GLe and BCG was demonstrated to achieve a complete cytostasis in 24 hours, and
      such effects were progressed in the subsequent 5 days. However, the pretreatment
      of GLe resulted in suppression of IL-6, IL-8, and MCP-1 secretions without
      affecting the cytotoxicity. Given that numerous proinflammatory cytokines are
      associated with the high side effects toll of BCG, results herein suggested the
      potential implications of GL to supplement the BCG immunotherapy in bladder
      cancer, for better efficacy and reducing side effects.

PMID- 22969823
TI  - Antidiabetic Effect of Morinda citrifolia (Noni) Fermented by Cheonggukjang in KK
      A(y) Diabetic Mice.
AB  - Antidiabetic effects of Morinda citrifolia (aka Noni) fermented by Cheonggukjang
      (fast-fermented soybean paste) were evaluated using a T2DM (type 2 diabetes
      mellitus) murine model. Six-week-old KK-Ay/TaJcl mice were randomly divided into
      four groups: (1) the diabetic control (DC) group, provided with a normal mouse
      diet; (2) the positive control (PC) group, provided with a functional health food
      diet; (3) the M. citrifolia (MC) group, provided with an MC-based diet; (4) the
      fermented M. citrifolia (FMC) group, provided with an FMC-based diet. Over a
      testing period of 90 days, food and water intake decreased significantly in the
      FMC and PC groups compared with the DC group. Blood glucose levels in the FMC
      group were 211.60-252.20 mg/dL after 90 days, while those in the control group
      were over 400 mg/dL after 20 days. In addition, FMC supplementation reduced
      glycosylated hemoglobin (HbA1c) levels, enhanced insulin sensitivity, and
      significantly decreased serum triglycerides and low-density lipoprotein (LDL)
      cholesterol. Furthermore, a fermented M. citrifolia 70% ethanolic extract (FMCE)
      activated peroxisome proliferator-activated receptor-(PPAR-) gamma and stimulated
      glucose uptake via stimulation of AMP-activated protein kinase (AMPK) in cultured
      C2C12 cells. These results suggest that FMC can be employed as a functional
      health food for T2DM management.

PMID- 22969824
TI  - Antiplatelet effects of qishen yiqi dropping pill in platelets aggregation in
      hyperlipidemic rabbits.
AB  - We investigated the effects of Qishen Yiqi Dropping Pill (QSYQ) on platelets
      aggregation and its possible mechanisms. Hyperlipidemic model in rabbits was
      produced by a high fat/cholesterol diet for 6 weeks, the therapeutic effect of
      QSYQ with 2.0 g/kg, 1.0 g/kg, and 0.5 g/kg was observed. Fourteen days after drug
      treatment, platelet aggregation induced by adenosine diphosphate (ADP),
      arachidonic acid (AA), and collagen (COLL) was significantly reduced in rabbits
      of model group. Moreover, beta-thromboglobulin (beta-TG) level decreased
      obviously but no significant change in P-selectin and platelet factor 4 (PF4)
      level, while QSYQ significantly decreased the ratio of thromboxane B2 (TXB(2)) to
      6-keto-prostaglandin F(1alpha) (6-Keto-PGF(1alpha)) and increased cyclic
      adenosine monophosphate (cAMP) level in rabbits. In summary, QSYQ can improve
      platelets aggregation and inhibit the over-release of beta-TG in hyperlipidemic
      rabbits; and the increased cAMP level may be involved in this process. These
      results suggest that the antiplatelet aggregation effect of QSYQ may be due to
      its ability to increase cAMP level for improving cAMP metabolism.

PMID- 22969825
TI  - Inhibitory effects of daiokanzoto (da-huang-gan-cao-tang) on p-glycoprotein.
AB  - We have studied the effects of various Kampo medicines on P-glycoprotein (P-gp),
      a drug transporter, in vitro. The present study focused on Daiokanzoto (Da-Huang
      Gan-Cao-Tang), which shows the most potent inhibitory effects on P-gp among the
      50 Kampo medicines studied, and investigated the P-gp inhibitory effects of
      Daiokanzoto herbal ingredients (rhubarb and licorice root) and their components
      by an ATPase assay using human P-gp membrane. Both rhubarb and licorice root
      significantly inhibited ATPase activity, and the effects of rhubarb were more
      potent than those of licorice root. The content of rhubarb in Daiokanzoto is
      double that in licorice root, and the inhibition patterns of Daiokanzoto and
      rhubarb involve both competitive and noncompetitive inhibition, suggesting that
      the inhibitory effects of Daiokanzoto are mainly due to rhubarb. Concerning the
      components of rhubarb, concentration-dependent inhibitory effects were observed
      for (-)-catechin gallate, (-)-epicatechin gallate, and (-)-epigallocatechin
      gallate. In conclusion, rhubarb may cause changes in the drug dispositions of P
      gp substrates through the inhibition of P-gp. It appears that attention should be
      given to the interactions between these drugs and Kampo medicines containing
      rhubarb as an herbal ingredient.

PMID- 22969826
TI  - Antitumor activities of kushen: literature review.
AB  - To discover and develop novel natural compounds with therapeutic selectivity or
      that can preferentially kill cancer cells without significant toxicity to normal
      cells is an important area in cancer chemotherapy. Kushen, the dried roots of
      Sophora flavescens Aiton, has a long history of use in traditional Chinese
      medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As) and
      kushen flavonoids (KS-Fs) are well-characterized components in kushen. KS-As
      containing oxymatrine, matrine, and total alkaloids have been developed in China
      as anticancer drugs. More potent antitumor activities were identified in KS-Fs
      than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor
      agents.

PMID- 22969827
TI  - Scutellaria baicalensis Extracts and Flavonoids Protect Rat L6 Cells from
      Antimycin A-Induced Mitochondrial Dysfunction.
AB  - Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron
      transport and can produce reactive oxygen species (ROS). ROS formation, aging,
      and reduction of mitochondrial biogenesis contribute to mitochondrial
      dysfunction. The present study sought to investigate extracts of Scutellaria
      baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they
      could protect mitochondria against oxidative damage. The viability of L6 cells
      treated with AMA increased in the presence of flavonoids and extracts of S.
      baicalensis. ATP production decreased in the AMA treated group, but increased by
      50% in cells treated with flavonoids (except wogonin) and extracts of S.
      baicalensis compared to AMA-treated group. AMA treatment caused a significant
      reduction (depolarized) in mitochondrial membrane potential (MMP), whereas
      flavonoid treatment induced a significant increase in MMP. Mitochondrial
      superoxide levels increased in AMA treated cells, whereas its levels decreased
      when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells
      treated with flavonoids and extracts of S. baicalensis increased their levels of
      protein expression compared with AMA-treated cells, especially water extracts
      performed the highest levels of protein expression. These results suggest that
      the S. baicalensis extracts and flavonoids protect against AMA-induced
      mitochondrial dysfunction by increasing ATP production, upregulating MMP, and
      enhancing mitochondrial function.

PMID- 22969828
TI  - Chinese Herbal Medicine in Treating Primary Sjogren's Syndrome: A Systematic
      Review of Randomized Trials.
AB  - Background. There is no curative treatment for primary Sjogren's syndrome (PSS).
      Chinese herbal medicine (CHM) is widely used in the treatment of PSS in China.
      Objective. To evaluate the effectiveness and safety of CHM for PSS. Methods.
      PubMed, Cochrane Library, China Knowledge Resource Integrated Database, Chinese
      Biomedical Database, Wanfang Data, and the Database for Chinese Technical
      Periodicals were searched for randomized controlled trials (RCTs) of CHM or CHM
      plus conventional medicine for PSS compared with placebo or conventional
      medicine. RevMan 5.0.17 was employed to conduct data analyses and assess
      homogeneity. Statistical models were chosen according to heterogeneity. Results.
      A total of 52 RCTs were included. The overall methodological quality of included
      trials was low. 49 trials reported response rates, of which 32 found significant
      improvements favoring CHM treatment against controls; 20 trials reported lacrimal
      function by Schirmer test scores, of which 16 trials reported a significant
      difference favoring CHM treatment. 21 trials reported salivary function by
      salivary flow rate, of which 10 reported significant favorable effects of CHM
      treatment. Other trials found no difference. The reported adverse effects of CHM
      included nausea, diarrhea, and other minor digestive symptoms, but more frequent
      adverse effects occurred in conventional medicine groups. Conclusions.
      Preliminary evidence from RCTs suggests the effect of CHM is promising for
      relieving symptoms, improving lacrimal and salivary function in PSS. However, the
      poor methodological quality of the included trials means that further well
      designed, multicentered, larger trials are needed.

PMID- 22969829
TI  - Can combination therapy of conventional and oriental medicine improve poststroke
      aphasia? Comparative, observational, pragmatic study.
AB  - The aim of the present study was to determine the effectiveness of oriental
      medicine therapy on poststroke aphasia. The outcome was measured as the delta
      value of the Aphasic Quotient score. Patients completed test at two timepoints:
      baseline and discharge time. Patients who received conventional therapy and
      language therapy were grouped in the Only Language Therapy group. Patients who
      received conventional therapy, language therapy, and an Oriental medicine regimen
      were grouped in the Combined oriental Medicine Therapy group. We compared the
      delta value of the Aphasic Quotient score between two groups. The Combined
      Oriental Medicine group exhibited a greater improvement than the Only Language
      Therapy group in the total Aphasic Quotient score and most subsection scores. In
      particular, there were statistically significant differences in total Aphasic
      Quotient score and subsections such as spontaneous speech, content delivery,
      comprehension, auditory verbal comprehension, and command performance. Among
      severe aphasic patients, the improvement of the Combined oriental Medicine group
      was better than that of the Only Language Therapy group. Through this study, we
      suggest combination therapy with the administration of oriental medicine and
      language therapy can be helpful in the treatment of post-stroke aphasic patients.

PMID- 22969830
TI  - Activation of Spinal alpha2-Adrenoceptors Using Diluted Bee Venom Stimulation
      Reduces Cold Allodynia in Neuropathic Pain Rats.
AB  - Cold allodynia is an important distinctive feature of neuropathic pain. The
      present study examined whether single or repetitive treatment of diluted bee
      venom (DBV) reduced cold allodynia in sciatic nerve chronic constriction injury
      (CCI) rats and whether these effects were mediated by spinal adrenergic
      receptors. Single injection of DBV (0.25 or 2.5 mg/kg) was performed into Zusanli
      acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg) was injected for 2
      weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low
      dose (0.25 mg/kg) did not produce any anticold allodynic effect, while a high
      dose of DBV (2.5 mg/kg) significantly reduced cold allodynia. Moreover, this
      effect of high-dose DBV was completely blocked by intrathecal pretreatment of
      idazoxan (alpha2-adrenoceptor antagonist), but not prazosin (alpha1-adrenoceptor
      antagonist) or propranolol (nonselective beta-adrenoceptor antagonist). In
      addition, coadministration of low-dose DBV (0.25 mg/kg) and intrathecal clonidine
      (alpha2-adrenoceptor agonist) synergically reduced cold allodynia. On the other
      hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably
      suppressed cold allodynia from 7 days after DBV treatment. This effect was also
      reversed by intrathecal idazoxan injection. These findings demonstrated that
      single or repetitive stimulation of DBV could alleviate CCI-induced cold
      allodynia via activation of spinal alpha2-adrenoceptor.

PMID- 22969832
TI  - Toxicity of a novel herbomineral preparation las01 on human cancer cell lines and
      its safety profile in humans and animals.
AB  - Polyhedral formulations based on Rasayana therapy described in Charaka Samhita
      showed remarkable improvement in quality of life of various cancer patients who
      have been found to be refractory or poor responders to modern chemotherapy and
      radiation treatment. One of the most recent novel herbomineral preparation, Las01
      prepared absolutely as per the instruction given in the ancient Ayurvedic
      literature has been found to be effective as a potent anticancer drug in the
      human cell lines, the MCF-7 and Hela cancer cell lines. This novel preparation of
      Las01 is also found to be devoid of toxicity both in animals as well as in human
      subjects, which is the main drawback of chemotherapeutic agents used in modern
      system of medicine. Our results warrant multicentric clinical trials on a large
      scale which seems to be a future promising drug to cure incurables cancer
      patients.

PMID- 22969833
TI  - Parametric mapping of brain tissues from diffusion kurtosis tensor.
AB  - Diffusion kurtosis imaging (DKI) is a new diffusion magnetic resonance imaging
      (MRI) technique to go beyond the shortages of conventional diffusion tensor
      imaging (DTI) from the assumption that water diffuse in biological tissue is
      Gaussian. Kurtosis is used to measure the deviation of water diffusion from
      Gaussian model, which is called non-Gaussian, in DKI. However, the high-order
      kurtosis tensor in the model brings great difficulties in feature extraction. In
      this study, parameters like fractional anisotropy of kurtosis eigenvalues (FAek)
      and mean values of kurtosis eigenvalues (Mek) were proposed, and regional
      analysis was performed for 4 different tissues: corpus callosum, crossing fibers,
      thalamus, and cerebral cortex, compared with other parameters. Scatterplot
      analysis and Gaussian mixture decomposition of different parametric maps are used
      for tissues identification. Diffusion kurtosis information extracted from
      kurtosis tensor presented a more detailed classification of tissues actually as
      well as clinical significance, and the FAek of D-eigenvalues showed good
      sensitivity of tissues complexity which is important for further study of DKI.

PMID- 22969834
TI  - A fuzzy model to interpret data of drive performances from patients with sleep
      deprivation.
AB  - The search for safe vehicles is increasing with both diffusion of high traffic
      density over the world and availability of new technologies providing
      sophisticated tools previously impossible to realize. Design and development of
      the necessary devices may be based on simulation tests that reduce cost allowing
      trials in many directions. A proper choice of the arrangement of the drive
      simulators, as much as of the parameters to be monitored, is of basic importance
      as they can address the design of devices somehow responsible for the drivers
      safety or, even their lives. This system setup, consisting of a free car
      simulator equipped with a monitoring system, collects in a nonintrusive way data
      of the car lateral position within the road lane and of its first derivative.
      Based on these measured parameters, the system is able to detect symptoms of
      drowsiness and sleepiness. The analysis is realized by a fuzzy inferential
      process that provides an immediate warning signal as soon as drowsiness is
      detected with a high level of certainty. Enhancement of reliability and
      minimisation of the false alarm rate are obtained by operating continuous
      comparison between learned driver typical modalities of operation on the control
      command of the vehicle the pattern recorded.

PMID- 22969831
TI  - Complementary medicine, exercise, meditation, diet, and lifestyle modification
      for anxiety disorders: a review of current evidence.
AB  - Use of complementary medicines and therapies (CAM) and modification of lifestyle
      factors such as physical activity, exercise, and diet are being increasingly
      considered as potential therapeutic options for anxiety disorders. The objective
      of this metareview was to examine evidence across a broad range of CAM and
      lifestyle interventions in the treatment of anxiety disorders. In early 2012 we
      conducted a literature search of PubMed, Scopus, CINAHL, Web of Science,
      PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and
      metaanalyses in the area. Our paper found that in respect to treatment of
      generalized anxiety or specific disorders, CAM evidence revealed current support
      for the herbal medicine Kava. One isolated study shows benefit for naturopathic
      medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive
      evidence, which is hampered by overall poor methodology. The breadth of evidence
      does not support homeopathy for treating anxiety. Strong support exists for
      lifestyle modifications including adoption of moderate exercise and mindfulness
      meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and
      nicotine offer encouraging preliminary data. In conclusion, certain lifestyle
      modifications and some CAMs may provide a beneficial role in the treatment of
      anxiety disorders.

PMID- 22969837
TI  - Dengue virus presence and surveillance in Okinawa (Review).
AB  - Recent reports have shown that the dengue virus (DENV) is a serious concern
      worldwide, especially in subtropical areas such as South-East Asia. With the
      development of transportation systems, the risk of DENV infection spreading is
      increasing. Since mosquitoes transmit DENV to humans, surveillance of DENV
      infected mosquito vectors is the most effective approach for preventing DENV.
      Okinawa is the only prefecture located in a subtropical region in Japan and
      historically shows continuous importation of DENV-related mosquito vectors. In
      this review, we describe the current and historical status of DENV in Okinawa.

PMID- 22969835
TI  - Beyond free radical scavenging: Beneficial effects of edaravone (Radicut) in
      various diseases (Review).
AB  - Free radicals play an important role in the pathogenesis of a variety of
      diseases; thus, they are an attractive target for therapeutic intervention in
      these diseases. Compounds capable of scavenging free radicals have been developed
      for this purpose and some, developed for the treatment of cerebral ischemic
      stroke, have progressed to clinical trials. One such scavenger, edaravone, is
      used to treat patients within 24 h of stroke. Edaravone, which can diffuse into
      many disease-affected organs, also shows protective effects in the heart, lung,
      intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging
      free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine
      effects in various diseases. Here, we critically review the literature on its
      clinical efficacy and examine whether edaravone should be considered a candidate
      for worldwide development, focusing on its effects on diseases other than
      cerebral infarction. Edaravone has been safely used as a free radical scavenger
      for more than 10 years; we propose that edaravone may offer a novel treatment
      option for several diseases.

PMID- 22969836
TI  - Glioblastoma multiforme: Molecular characterization and current treatment
      strategy (Review).
AB  - Glioblastoma multiforme (GBM) is the most common and lethal malignant primary
      brain tumor. It is classified by the World Health Organization (WHO) in the group
      of diffusely infiltrating astrocytomas, representing up to 50% of all primary
      brain gliomas, and carries the poorest prognosis. Aberrant genetic events and
      signaling pathways have clearly demonstrated that GBM is highly anaplastic and a
      morphologically highly heterogeneous tumor. Understanding the genetic
      alterations, specific molecular biomarkers and proliferative pathways may promote
      therapeutic development for the management of GBM. Age, Karnofsky performance
      score, histology, position and the extent of tumor resection have been identified
      as potential prognostic factors for patients with GBM. In this study, we review
      the molecular characterization of tumor cells, the current standard of care for
      patients diagnosed with GBM, including gross or near-total resection of the
      tumor, followed by radiotherapy, stereotactic brachytherapy, chemotherapy and new
      targeted therapies. Thus, we conclude that multimodal approaches for the
      treatment of patients with GBM may significantly improve their prognoses.

PMID- 22969838
TI  - Modulation of estrogenic action in clear cell carcinoma of the ovary (Review).
AB  - Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma
      (EAC), are the common histology in ovarian cancer patients who have associated
      endometriosis. However, both tumor types have distinct clinicopathological
      characteristics and molecular phenotypes. EAC is predominantly positive for
      estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This
      study reviews the current understanding of the role of the ER information in the
      pathogenesis of CCC, as well as the English language literature for biochemical
      studies on ER expression and estrogenic action in CCC. The iron-mediated
      oxidative stress occurs due to repeated hemorrhage in endometriosis, then this
      compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be
      observed. There are a number of factors that interfere with ER expression and
      estrogen activity, which include DNA methylation of the promoter region, histone
      deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase
      activity. Loss of estrogen function may be a turning point in CCC progression and
      aggressiveness.

PMID- 22969839
TI  - Prognostic significance of monocarboxylate transporter 4 expression in patients
      with colorectal cancer.
AB  - Cancer cells generally have a high rate of glycolysis and produce larger
      quantities of lactate as compared to the surrounding normal cells.
      Monocarboxylate transporter 4 (MCT4) is one of the proton pumps exchanging the
      lactate through the plasma membrane. The prognostic significance of MCT4
      expression has not been evaluated in patients with colorectal cancer (CRC).
      Surgical specimens from 105 CRC patients were immunohistochemically stained using
      a polyclonal anti-MCT4 antibody. The relationships among the MCT4 expression,
      clinicopathological factors and prognosis were evaluated. A total of 53 (50.5%)
      of the 105 patients with CRC were determined to have tumors positive for MCT4
      expression. The expression of MCT4 significantly correlated with the tumor size,
      depth of invasion, lymph node metastasis, distant metastasis and TNM staging. The
      survival rate of the patients who were positive for MCT4 expression was
      significantly lower than that of patients with negative MCT4 expression. Positive
      MCT4 expression was a significantly poor prognostic factor, as determined by both
      univariate and multivariate analyses. Therefore, positive MCT4 expression appears
      to be a useful marker for tumor progression and prognosis in patients with CRC.

PMID- 22969840
TI  - Comparative study of multi-slice CT angiography with digital subtraction
      angiography in the blood supply of meningiomas.
AB  - Evaluation of multi-slice CT angiography (MSCTA) and digital subtraction
      angiography (DSA) was made through the comparison of the two methods in detecting
      the blood supply of meningiomas, providing further clues for the improved
      application of MSCTA and DSA in the blood supply of meningiomas. In this study,
      20 patients with meningiomas underwent CT angiography by 16-slice spiral CT and
      inspection 1 week later using DSA. The blood supply of the meningiomas (including
      the tumor feeding arteries, draining veins, venous sinuses, vessels around the
      tumor and skull-shaped images, such as comparative evaluation) was compared. The
      results showed that MSCTA and DSA inspection clearly depicted tumor feeding
      arteries, draining veins and venous sinuses in all 20 patients. DSA was slightly
      more effective than MSCTA in displaying fine branches, and DSA had obvious
      advantages over MSCTA in displaying vessels near the skull. In the display of the
      tumor's compression and pushing over its peripheral vasculature, MSCTA had the
      three-dimensional advantage, although in displaying parasagittal sinus
      meningiomas, it may overestimate the presence of venous sinus invasion due to the
      impact of bone structure. This does not affect DSA. MSCTA accurately assesses the
      relationship between the tumor and the bone, and provides three-dimensional
      images for the pre-operative simulation of surgical approaches. Taken together,
      MSCTA and DSA are both able to provide important information, such as accurate
      visualization of tumor-feeding arteries, draining veins and venous sinuses, with
      high consistency. MSCTA is more advantageous in the depiction of three
      dimensional relationships between the tumor and peripheral vessels and skull.
      Compared to DSA, MSCTA is non-invasive, faster and less costly.

PMID- 22969842
TI  - Increased Sox2 copy number in lung squamous cell carcinomas.
AB  - The transcription factor Sox2 is necessary for foregut morphogenesis. Sox2 is
      also required for the normal development of the trachea and lung. Recently, Sox2
      amplifications were investigated using large-scale single nucleotide polymorphism
      arrays in esophageal and lung cancer. We hypothesized that Sox2 overexpression
      might be correlated with clinicopathological features of lung cancers. The
      increased copy number of the Sox2 gene was analyzed by real-time polymerase chain
      reaction amplifications in 127 surgically treated non-small cell lung cancer
      cases from Nagoya City University Hospital, Japan. A total of 87 squamous cell
      carcinoma (SCC) cases were involved. An increased Sox2 gene copy number was found
      in 42 (33.1%) lung cancer patients. Increased Sox2 copy number status was
      significantly correlated with gender (females, 9.5% vs. males, 34.1%; p=0.0026),
      smoking status (never smoker, 4.8% vs. smoker, 32.9%; p=0.0003) and pathological
      subtypes (squamous cell carcinoma, 44.8% vs. non-squamous cell carcinoma, 7.5%;
      p<0.0001). However, among the SCCs, the Sox2 copy number status was not
      significantly correlated with gender, smoking status, pathological stage or
      differentiation status. An increased Sox2 copy number is common within SCC.

PMID- 22969841
TI  - Stage-dependent suppression of the formation of dentin-resorbing multinuclear
      cells with migration inhibitory factor in vitro.
AB  - The macrophage migration inhibitory factor (MIF) is a crucial mediator of immune
      responses and is known to play a pivotal role in cell proliferation and
      differentiation. In this study, we assessed whether MIF exerts regulatory effects
      on osteoclast formation in bone marrow cells and, if so, by what mechanism. Bone
      marrow cells were either co-cultured with MC3T3-E1 cells or cultured with
      macrophage-colony stimulating factor (M-CSF) and the soluble form of the receptor
      activator of the nuclear factor-kappaB ligand (RANKL). Under the influence of
      MIF, the formation of osteoclastic multinuclear cells was examined. The number of
      multinuclear TRAP-positive cells formed in the co-culture was significantly
      reduced when MIF (>=0.1 MUg/ml) was exogenously applied during the third and
      fourth days of the 6-day cultivation period. MIF affected neither the number of
      mononuclear TRAP-positive cells induced with M-CSF and RANKL, nor the expression
      of RANKL and osteoprotegerin in MC3T3-E1 cells. TRAP-positive cells cultured on
      dentin slices with MIF showed lower dentin-resorbing activity than those cultured
      without MIF. These results suggest that MIF has no regulatory roles in the
      differentiation of bone marrow cells to mononuclear TRAP-positive cells, but has
      inhibitory effects on the formation of mature osteoclasts by preventing cell
      fusion, which may eventually interfere with the osteoclast-mediated dentin
      resorption.

PMID- 22969843
TI  - Kuromoji (Lindera umbellata) essential oil-induced apoptosis and differentiation
      in human leukemia HL-60 cells.
AB  - Essential oils diluted from certain plants have been shown to have antitumor
      activity against several human tumor cell lines. Kuromoji (Lindera umbellata)
      essential oil (KEO) has long been used in Japan as a traditional medicine. KEO
      and its major chemical constituent, linalool, were investigated in this study for
      their ability to induce apoptosis and differentiation in human leukemia HL-60
      cells. HL-60 cells were treated with 5 or 50 MUg/ml KEO or linalool for 24 or 48
      h. Then, cell proliferation and apoptosis induction were estimated. In addition,
      HL-60 cells are known to differentiate into granulocyte or monocytes by a variety
      of compounds. Therefore, the effect of KEO or linalool on differentiation of HL
      60 cells was assessed by Giemsa stain and a nitroblue tetrazolium reduction
      assay. Cells treated with KEO or linalool for 48 h showed significantly
      suppressed cell proliferation, with induced apoptosis. Moreover, KEO and linalool
      promoted cell differentiation. Treatment with KEO cells at the same dose as
      linalool showed an almost identical effect on HL-60 cells. These results suggest
      that KEO and linalool have efficacy as anticancer therapeutic products.

PMID- 22969844
TI  - A population-based study of gefitinib in patients with postoperative recurrent
      non-small cell lung cancer.
AB  - There is no standard treatment and there are no clearly defined guidelines for
      the treatment of postoperative recurrent non-small-cell lung cancer (NSCLC). We
      performed a retrospective population-based study to assess the benefits of
      treatment with gefitinib in patients with a postoperative recurrence of NSCLC in
      general clinical practice. This retrospective population-based study was
      conducted on patients with postoperative recurrent NSCLC who had been treated
      with gefitinib at 14 institutions in Ibaraki Prefecture between July 2002 and
      September 2007. The objective response rate to gefitinib therapy was 37.6% for
      local and distant recurrence. The median survival time following the start of
      gefitinib therapy was 12 months, and the one-year and two-year survival rates
      were 48.9 and 28.9%, respectively. The median survival time of the females was 19
      months, and the median survival time of the males was 9 months (p=0.002).
      Univariate analysis showed that female gender, adenocarcinoma, a performance
      status (PS) of 0-1 and absence of smoking history were favorable prognostic
      factors. Only female gender and a PS of 0-1 were independent statistically
      significant prognostic factors in the multivariate analysis. The rate of greater
      than grade 1 interstitial lung damage as an adverse event was 3.5%. Gefitinib is
      a feasible treatment for postoperative recurrent NSCLC in general clinical
      practice, and a good response and prolonged survival were obtained, similar to
      the findings reported in published clinical studies that were conducted on highly
      selected patients.

PMID- 22969845
TI  - Objective evaluation of the alleviating effects of Goshajinkigan on peripheral
      neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative
      study.
AB  - Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits
      neurotoxicity and causes peripheral neuropathy at a high frequency, which is
      difficult to cope with. In this study, we investigated the efficacy of
      Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced
      peripheral neuropathy. The subjects included in our study were patients with
      ovarian or endometrial cancer who underwent TC therapy and developed peripheral
      neuropathy. The patients were randomly divided into Group A, comprising of 14
      patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin
      B12 + Goshajinkigan treatment). The observation period was 6 weeks following
      treatment initiation, and the evaluation items were as follows: i) the current
      perception threshold (CPT value) of the peripheral nerve, ii) visual analogue
      scale for numbness, iii) National Cancer Institute Common Terminology Criteria
      for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the
      subjective symptoms of peripheral neuropathy (functional assessment of cancer
      therapy-taxane). These were compared between the groups and no significant
      differences were noted in any item. However, CTCAE grade 3 neurotoxicity
      developed in 2 patients (14.3%) after 6 weeks of administration in Group A,
      whereas no neurotoxicity was observed in Group B. When the change in the
      frequency of abnormal CPT ratio at 6 weeks of administration from that before
      treatment was compared between the groups, the frequency of abnormal value was
      significantly lower in Group B than in Group A (p<0.05). This suggests that
      Goshajinkigan inhibits the progression of peripheral neuropathy.

PMID- 22969846
TI  - Predictive significance of the proportion of ER-positive or PgR-positive tumor
      cells in response to neoadjuvant chemotherapy for operable HER2-negative breast
      cancer.
AB  - Estrogen receptor (ER) and progesterone receptor (PgR) status are predictive
      factors for the clinical and pathological response to neoadjuvant chemotherapy
      for operable breast cancer. However, it remains unclear as to how the proportion
      of ER-positive or PgR-positive tumor cells affects the response to neoadjuvant
      chemotherapy. We examined the correlation of the proportion of ER-positive or PgR
      positive tumor cells with the clinical and pathological response to neoadjuvant
      chemotherapy for operable human epidermal growth factor receptor 2 (HER2)
      negative breast cancer. From April 2002 to October 2010, 103 patients received
      neoadjuvant chemotherapy containing epirubicin and taxane in our clinic. A
      clinical response was observed in 86 (83%) patients, and a pathological complete
      response (pCR) was observed in 16 (16%) patients. Fourteen (30%) of 46 patients
      with ER-negative tumors achieved pCR and 15 (26%) of 57 patients with PgR
      negative tumors achieved pCR. Patients with more than 30% ER-positive tumor cells
      or more than 1% PgR-positive tumor cells did not achieve pCR. No significant
      correlation was observed between pCR and the menopausal status, tumor size, grade
      and Ki-67 expression. In univariate analysis, pCR was associated with the ER
      status (p=0.001), PgR status (p=0.0001) and chemotherapy regimens (p=0.03).
      Multivariate analysis revealed that ER and PgR status were significant factors
      for pCR, and patients with ER-negative tumors were 18.6 times more likely to
      achieve pCR than those with greater than or equal to 30% ER-positive tumor cells
      (p=0.006; 95% confidence interval 2.3-149.9). We demonstrated a predictive
      significance of the proportion of ER-positive or PgR-positive tumor cells in the
      response to neoadjuvant chemotherapy for operable HER2-negative breast cancer. ER
      negativity (<1%) was a significant predictive factor for achieving pCR in
      multivariate analysis. Conversely, patients with more than 30% ER-positive tumor
      cells or more than 1% PgR-positive tumor cells may not achieve pCR.

PMID- 22969847
TI  - Serum albumin is present at higher levels in alcoholic liver cirrhosis as
      compared to HCV-related cirrhosis.
AB  - Residual hepatic functional reserve in cirrhotic patients is generally evaluated
      by a multivariate scoring system (Child-Pugh classification), which includes
      serum albumin levels as a variable. However, several patients show discrepancies
      between serum albumin levels and the progression of liver fibrosis, especially
      those with alcoholic cirrhosis. To assess whether hepatic capacity of protein
      synthesis varies with the etiology of cirrhosis, serum albumin and cholinesterase
      levels, and prothrombin time were compared between alcoholic cirrhosis and
      hepatitis C virus (HCV)-related cirrhosis. To minimize the influence of
      malnutrition and extrahepatic platelet destruction, patients with hepatocellular
      carcinoma, uncontrolled diabetes, appetite loss and/or splenal longitudinal size
      >15 cm were excluded. The patients with compensated liver cirrhosis were divided
      into three groups as follows: alcohol(+)/HCV(+) (alcohol + HCV group; n=31),
      alcohol(-)/HCV(+) (HCV group; n=31) and alcohol(+)/HCV(-) (alcohol group; n=27).
      These groups were adjusted with respect to age, gender, body mass index and
      platelet count. Serum albumin levels in the alcohol group were significantly
      higher than those in the HCV group, with a difference of approximately 0.5 g/dl
      in every class of platelet count. The correlation of the alcohol + HCV group was
      intermediate between the alcohol and HCV groups. On the other hand, the
      correlations between serum cholinesterase levels and platelet counts were similar
      among the three groups. The prothrombin time was also comparable among the
      groups. Accordingly, serum albumin levels were higher in patients with alcoholic
      cirrhosis and alcohol consumption should be carefully considered when evaluating
      hepatic functional reserve.

PMID- 22969848
TI  - Pathological observations of lung inflammation after administration of IP-10 in
      influenza virus- and respiratory syncytial virus-infected mice.
AB  - Pneumonia is a common complication of influenza virus infection and a common
      cause of death of patients. The aim of this study was to test the hypothesis that
      interferon-gamma-inducible protein-10 (IP-10) is an important chemokine in the
      development of airway inflammation caused by certain viruses. Mice were infected
      with influenza virus after administration of murine IP-10 and the severity of
      pneumonia was compared with the group which was infected with influenza virus
      alone. Another mice group was infected with respiratory syncytial virus (RSV)
      after injection of IP-10 and also the severity of pneumonia was compared to the
      group which was infected with RSV alone. The mice infected with influenza virus
      or RSV after administration of IP-10 presented with more fulminant and
      necrotizing diffuse alveolar and bronchiole damage with lymphocyte infiltration.
      Our results indicate that IP-10 is an important chemokine and is associated with
      the severity of pneumonia caused by certain viruses.

PMID- 22969849
TI  - Liver Yin deficiency tonifying herbal extract induces apoptosis and cell
      senescence in Bel-7402 human hepatocarcinoma cells.
AB  - Liver cancer ranks as the fifth most prevalent malignancy of all cancers
      worldwide. According to the principles of traditional Chinese medicine, liver Yin
      deficiency is a common clinical syndrome of liver cancer, and tonifying liver Yin
      is a common treatment method for liver cancer. However, no hepatocarcinoma
      specific liver Yin tonifying formula has yet been established. In the present
      study, we established a liver cancer-specific combination of herbs, which we term
      liver Yin tonifying formula (LYTF). We found that LYTF inhibits the proliferation
      of Bel-7402 cells in a dose- and time-dependent manner. LYTF induces apoptosis in
      Bel-7402 cells, which is accompanied by activation of caspases-8, -9 and -3. Pan
      caspase blocking completely abrogates LYTF-induced apoptosis and partially
      abrogates LYTF-induced proliferation inhibition. LYTF also induces cell
      senescence, as indicated by a large and flattened morphology, senescence
      activated beta-galactosidase-positive staining and G0/G1 cell cycle arrest,
      accompanied by the up-regulation of p16 and p21 and the down-regulation of
      retinoblastoma protein phosphorylation. These findings suggest that LYTF is
      effective in inhibiting the growth and survival of hepatocarcinoma cells through
      the induction of apoptosis and cell senescence. Our study also provides insight
      into traditional Chinese medicine methods used for the treatment of liver cancer.

PMID- 22969850
TI  - Predictive value of p53 expression in the risk of malignant gastrointestinal
      stromal tumors: Evidence from 19 studies.
AB  - The current published data on p53 expression and its predictive value in the risk
      of malignant gastrointestinal stromal tumors (GIST) has are inconclusive. To
      derive a more precise estimation of the correlation between p53 and the
      biological behavior of GIST, a meta-analysis was performed. Studies were
      identified by searching PubMed and Embase. Inclusion criteria were GIST patients,
      and the evaluation of p53 expression and risk of malignancy. The odds ratio (OR)
      for a positive rate of p53 in the benign group vs. that in the malignant group
      and the ORs for the positive rate of p53 in the National Institutes of Health
      (NIH) very low risk + low risk group (VL+L) vs. the NIH intermediate risk + high
      risk (I+H) group were calculated with a 95% confidence interval (CI) for each
      study as an estimation of the predictive value of p53. A total of 19 studies
      including 1163 patients were involved in this meta-analysis. The overall OR for
      the positive rate of p53 in the malignant group vs. the benign group revealed
      that significantly elevated risks of positive p53 in the malignant group were
      achieved (OR 0.14, 95% CI: 0.06-0.31, P<0.00001, P(heterogeneity)=0.86).
      Moreover, significantly elevated risks of correlation between p53 expression and
      the NIH I+H group were achieved in the comparison of the NIH VL+L group vs. the
      NIH I+H group (OR, 0.25; 95% CI, 0.17-0.38; P<0.00001, P(heterogeneity)=0.04).
      The results indicate that p53 expression correlates with poor prognosis in GIST
      and has a close relationship within the NIH I+H group.

PMID- 22969851
TI  - Polymorphisms of IGFI contribute to the development of ischemic stroke.
AB  - Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal
      brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly.
      In this study, we investigated whether single nucleotide polymorphisms (SNPs) of
      the IFG1 gene are associated with the development and clinical features of IS in
      a Korean population. A total of 119 patients with IS and 289 control subjects
      were recruited. Stroke patients were classified into subgroups according to the
      scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and >=6) and
      the Modified Barthel Index (MBI; <60 and >=60). Among the SNPs of the IFG1 gene,
      five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron),
      rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3'
      untranslated region; 3'UTR). Multiple logistic regression models were conducted
      to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were
      used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values.
      Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After
      Bonferroni correction (p(c)), the A and G alleles of rs2162679 and rs6214 had
      significant differences between patients with IS and the controls [rs2162679, OR
      (95% CI) = 1.64 (1.17-2.31), p=0.004, p(c)=0.02; rs6214, OR (95% CI) = 1.52 (1.12
      2.07), p=0.007, p(c)=0.035], respectively. However, the five selected SNPs were
      not related to the NIHSS and MBI scores. These results suggest that IGF1 may be
      associated with the development of IS.

PMID- 22969852
TI  - Effects of Etlingera elatior extracts on lead acetate-induced testicular damage:
      A morphological and biochemical study.
AB  - Lead causes damage to the whole body by inducing oxidative stress. This includes
      the testis, in which spermatogenesis is affected. Etlingera elatior, a consumable
      plant that is being extensively studied for its high anti-oxidant properties, was
      tested against the effect of lead acetate in experimental rats. Rats were divided
      into groups consisting of a control, lead acetate only, Etlingera elatior
      treatment only, concurrent treatment of lead acetate and Etlingera elatior, post
      treatment of lead acetate followed by Etlingera elatior and preventive group of
      Etlingera elatior followed by lead acetate. The substances were administered for
      14 days and the effects were measured by protein carbonyl content (PCC),
      superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity in the
      testis, as well as the testosterone level in the serum. Histological changes in
      the testis were also observed. Results showed that Etlingera elatior induced a
      significant reduction in the testis PCC activity, while at the same time it
      significantly increased the activities of SOD and GPx in the testis, and the
      testosterone level in the serum. Etlingera elatior also improved the histology of
      the testis when compared to the lead acetate-treated group. On the whole,
      Etlingera elatior is effective against oxidative damage caused by lead acetate in
      the testis.

PMID- 22969853
TI  - Clinical application of CyberKnife for high-risk central nervous system tumors: A
      clinical trial report of 60 cases.
AB  - The objective of the present study was to evaluate the application potential of
      CyberKnife for high-risk tumors of the central nervous system and to analyze the
      effectiveness of CyberKnife in relation to dose recovery and gain division
      (times). A total of Eighty-one targeted areas from 139 central nervous tumor
      lesions in 60 patients were treated with I-VI ranged CyberKnife for 1 week.
      Following CyberKnife treatment, imaging tests revealed a decrease in tumor
      volume, reduction of central nervous system symptoms and an increase in the life
      quality of patients. The advantages of CyberKnife include non-invasiveness,
      individualized treatment, flexibility, high accuracy and rapid treatment.
      CyberKnife produces slight damage and a favorable therapeutic effect and expands
      our concepts concerning precise radiotherapy for tumors. It is an indispensable
      method for personalized tumor treatment.

PMID- 22969854
TI  - Development of a survival prediction model for gastric cancer using serine
      proteases and their inhibitors.
AB  - Proteolytic enzymes play a key role in the metastatic stage of gastric cancer
      (GC). In this study, we aimed to identify the serine proteases (SPs) and their
      inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases
      of GC were initially detected by cDNA microarray. The results of the
      differentially expressed SPs and their inhibitor genes from the microarrays were
      confirmed by real-time PCR. The status of the immunohistochemical staining of the
      confirmed genes in patients with complete data was used to develop a survival
      prediction model. Finally, the prediction model was tested in different groups of
      GC patients. As a result, seven genes, SERPINB5, KLK10, KLK11, HPN, SPINK1,
      SERPINA5 and PRSS8, were considered as GC progression-related genes. A survival
      prediction model including the immunohistochemical scores of three genes and the
      tumor node metastasis (TNM) score was developed: Survival time (months) = 88.8607
      + 2.6395 SERPINB5 - 12.0772 KLK10 + 13.7562 KLK11 - 7.0318 TNM. In conclusion,
      SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8 were GC progression
      related SPs or serpin genes. The model consisting of the expression profiles of
      three genes extracted from the microarray study accompanied by the TNM score
      accurately predicts surgery-related survival of GC patients.

PMID- 22969855
TI  - Down-regulation of CXCR7 inhibits the growth and lung metastasis of human
      hepatocellular carcinoma cells with highly metastatic potential.
AB  - CXCR7, a recently identified chemokine receptor, has been implicated in directing
      cancer metastasis. In the present study, the potential roles of CXCR7 in the
      growth and metastasis of hepatocellular carcinoma (HCC) were evaluated. A
      chemokine receptor gene chip was used to compare the expression of CXCR7 in HCC
      cell lines with different metastatic potential. Effects of targeting CXCR7 by RNA
      interference (RNAi) on the proliferation and metastasis of HCCLM3 cells were
      observed in vitro and in vivo. CXCR7 expression in 116 specimens from patients
      with or without metastatic HCC was assessed by tissue microarray. As a result,
      the gene chip showed that expression of CXCR7 was significantly higher in the
      highly metastatic HCCLM3 cells, which was confirmed by real-time RT-PCR and
      Western blotting. Chemotaxis assays showed that HCCLM3 cells responded to SDF
      1alpha from 1 to 100 MUg/l and lung extractions (1 g/l). Furthermore, down
      regulation of CXCR7 in HCCLM3 cells by RNAi inhibited the proliferation and
      invasion of tumor cells in vitro. Moreover, CXCR7 knockdown significantly reduced
      the activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. RNAi
      of CXCR7 in the HCCLM3 cells also decreased the growth of tumors and the number
      of lung metastases in nude mice. The tissue microarray showed that HCCs with high
      expression of CXCR7 were prone to metastasize to the lung. These findings suggest
      that CXCR7 plays critical roles in the growth and metastasis of HCC. RNAi of
      CXCR7 inhibits the growth and invasion of tumor cells, which indicates that CXCR7
      may be a potential molecular target for use in HCC therapy.

PMID- 22969856
TI  - Smoking and hepatocellular carcinoma mortality.
AB  - The association between cigarette smoking and mortality from hepatocellular
      carcinoma (HCC) is ambiguous. We analyzed the association between smoking and
      mortality in HCC patients seen at our center. We collected data retrospectively
      on patients diagnosed with HCC between 2002 and 2009. We estimated the
      association of smoking history with demographic, clinical and treatment factors.
      We then modeled these factors as predictors of mortality. Among smokers, we
      analyzed the effects of pack-year history and cessation times on survival. Two
      hundred and twenty-three out of 444 patients with HCC had a history of smoking.
      Smokers were more likely to be younger at diagnosis, to have alpha fetoprotein
      (AFP) values less than the median, and to have had surgery (p=0.04) compared to
      non-smokers. In a Cox model, younger age, lower AFP and Child's Class were all
      independently predictive of survival, but smoking was not. Smokers with over 20
      pack-years did not have worse survival than lighter smokers, and cessation times
      also did not affect survival after controlling for age. We found a significant
      interaction between smoking and drinking. In our data, smoking was not
      independently associated with HCC survival in a multivariable model. Smoking was
      associated with favorable prognostic features which likely outweighed any
      independent effect of smoking.

PMID- 22969857
TI  - Estimation of molecular upper remission limit for monitoring minimal residual
      disease in peripheral blood of acute myeloid leukemia patients by WT1 expression.
AB  - To date, approximately one half of acute myeloid leukaemia (AML) patients do not
      have a suitable specific molecular marker for monitoring minimal residual disease
      (MRD). The Wilm's tumour gene (WT1) has been suggested as a possible molecular
      marker of MRD in AML. The expression of WT1 in peripheral blood (PB) was measured
      using quantitative real-time reverse transcription-polymerase chain reaction in
      peripheral leukocytes from 151 patients with AML at diagnosis. WT1 expression was
      significantly elevated, i.e. up to 3 orders of magnitude in the majority (80%) of
      AML patients at diagnosis compared to the PB of healthy donors. Sequence samples
      of the long-term followed-up AML patients treated with chemotherapy and/or
      allogeneic bone marrow transplantation were analysed for WT1 expression. The
      results revealed that the hematological relapses were preceded (median, 1.8
      months) by an increase in WT1 gene expression. For the practical utility of this
      gene as a molecular marker of relapse, it was necessary to determine an upper
      remission limit, crossing which would signal hematological relapse. The upper
      remission limit was determined in our set of patients to be 0.02 WT1/ABL. The AML
      patients who consequently relapsed crossed this upper remission limit; however,
      those in permanent remission did not. Therefore, this upper remission limit could
      be taken as the border of molecular relapse of AML patients. Moreover,
      insufficient decline of WT1 expression under the upper remission limit following
      induction and/or consolidation therapy was associated with markedly high risk of
      relapse. The results show that our upper remission limit can be taken as the
      border of molecular relapse of AML patients and WT1 levels following initial
      therapy as a beneficial prognostic marker.

PMID- 22969858
TI  - Quality of life in advanced non-small cell lung cancer patients receiving
      palliative chemotherapy: A meta-analysis of randomized controlled trials.
AB  - For advanced non-small cell lung cancer (NSCLC) patients, the only treatment
      option is palliative therapy, with the aim of prolonging overall survival and
      improving disease-related symptoms and quality of life (QOL). However, to date,
      the effect of palliative care on QOL has not yet been thoroughly examined, and
      there has been no meta-analysis of previous studies reporting QOL outcomes
      following palliative care. We consider that it is important to evaluate not only
      survival and/or response rates, but also QOL in patients with advanced NSCLC
      receiving palliative chemotherapy. The aim of the present study was to obtain
      useful information for the selection of suitable chemotherapy regimens for
      advanced NSCLC patients, taking into consideration QOL, and to demonstrate the
      importance of QOL assessments during treatment. We performed a meta-analysis of
      QOL outcomes following treatments that compared carboplatin- to cisplatin-based
      chemotherapy. Trials were eligible for analysis if they had compared carboplatin-
      to cisplatin-based chemotherapy in advanced NSCLC patients who had not received
      prior chemotherapy, and if these studies reported QOL data. In the six trials
      eligible for analysis, 2,405 patients were randomized to receive cisplatin-based
      or carboplatin-based chemotherapy. The patients who received carboplatin-based
      chemotherapy had higher global QOL and less severe symptoms than those who
      received cisplatin-based chemotherapy. The survival rate, which was the primary
      outcome in clinical trials, and the response rate did not differ significantly
      between the two treatment groups. It is important to evaluate QOL in addition to
      the survival and response rates for advanced NSCLC, particularly when the
      treatment is palliative.

PMID- 22969859
TI  - Suppression of HIF-1alpha expression and radiation resistance in acute hypoxic
      conditions.
AB  - Recently, it has become clear that acute hypoxia affecting radioresistance exists
      widely in tumor tissues. Concurrently, hypoxia-inducible factor-1alpha (HIF
      1alpha) is recognized as an essential transcriptional factor, enabling cells to
      survive through hypoxia. However, it is unclear as to whether HIF-1alpha plays a
      direct role in the radioresistance caused by acute hypoxia. Therefore, in this
      study, we investigated the in vitro response of the human lung adenocarcinoma
      cell line, A549, to ionizing radiation in an experimental model that imitates
      acute hypoxia in the presence and absence of HIF-1alpha expression, using the HIF
      1alpha inhibitor 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1).
      Cells were treated with or without 10 MUM YC-1 for 2 h. Cells were exposed to
      either 95% N(2) and 5% CO(2) (hypoxic condition of <0.1 mmHg) or atmospheric air
      (normoxic condition) for 1 h, and irradiated with 2, 5 and 10 Gy. Western blot
      analysis revealed that, without YC-1, cells exposed to hypoxic conditions
      expressed increased levels of HIF-1alpha compared with those exposed to normoxic
      conditions. Under hypoxic conditions, HIF-1alpha expression was suppressed by YC
      1 to the same extent as that observed in cells exposed to normoxic conditions
      without YC-1. Clonogenic survival assay revealed that under hypoxic conditions
      there was no significant difference between the surviving fraction of cells
      treated with YC-1 and without YC-1 at any dose point examined. The oxygen
      enhancement ratio at 10% surviving fraction was calculated as 2.7 and 2.6 in the
      presence and the absence of YC-1, respectively. These results indicate that HIF
      1alpha itself is not an immediate cause of acute hypoxia-induced radioresistance
      in A549 cells.

PMID- 22969860
TI  - TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells
      in the presence of curcumin.
AB  - The present study was designed to observe the initiation of mitophagy in tumor
      cells after ultrasound treatment in the presence of curcumin under transmission
      electron microscopy. Nasopharyngeal carcinoma CNE2 cells were incubated with 10
      MUM curcumin and then exposed to ultrasound for 8 sec at an intensity of 0.46
      W/cm(2). Severely swollen mitochondria, disrupted mitochondria and mitophagy were
      noted in the CNE2 cells after ultrasound treatment in the presence of curcumin.
      Our findings demonstrated that ultrasound treatment in the presence of curcumin
      significantly initiated mitophagy in CNE2 cells, which suggests that mitophagy
      serves as an important event in the process of cell death of nasopharyngeal
      carcinoma cells.

PMID- 22969861
TI  - microRNA-99b acts as a tumor suppressor in non-small cell lung cancer by directly
      targeting fibroblast growth factor receptor 3.
AB  - microRNAs (miRNAs) play a significant role in cancer development and progression
      by regulating the expression of proto-oncogenes or tumor suppressor genes. Our
      previous study using microarrays demonstrated that miR-99b was downregulated in
      patients with lung cancer. To assess whether or not miR-99b has a functional role
      in lung cancer, we determined the expression of miR-99b and fibroblast growth
      factor receptor 3 (FGFR3), which is a predicted target of miR-99b in public
      algorithms in human lung cancer tissues. miR-99b was downregulated and FGFR3 was
      upregulated in lung cancer patients. We demonstrated that the overexpression of
      miR-99b induced a reduction in FGFR3 expression and confirmed the target
      specificity between miR-99b and the FGFR3 3'-untranslated region by luciferase
      reporter assay. In addition, the growth rate in miR-99b precursor-treated cells
      was lower compared to the negative controls. Taken together, these results
      suggest that miR-99b may be a tumor suppressor through the downregulation of
      FGFR3. miR-99b may be a potent tumor suppressor and may be a potential
      therapeutic tool for patients with lung cancer.

PMID- 22969862
TI  - Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast
      cancer in xenograft-bearing mice.
AB  - In the present study, we aimed to investigate the tumor-inhibiting effects of
      recombinant human endostatin (rhES) combined with paclitaxel-cisplatin (TP
      regimen) on human breast cancer in xenograft-bearing nude mice. A total of 24
      mice bearing human breast cancer xenografts were administered both rhES and TP,
      TP alone, rhES alone or saline. The tumor growth inhibition was observed. Serum
      vascular endothelial growth factor (VEGF) levels and microvessel density (MVD)
      were determined by ELISA and immunohistochemistry, respectively. Cell apoptosis
      was detected using terminal deoxynucleotidyl transferase dUTP nick end-labeling
      (TUNEL) staining. Survival time was observed in another 24 nude mice with the
      same treatment. MVD expression in the group administered rhES and TP was lower
      than that in the other groups (P<0.05); serum VEGF levels in the combined drug
      group were lower compared to the other groups; the apoptotic index increased in
      the combined drug group. We conclude that the effect of the TP regimen combined
      with rhES on breast cancer is better than that of the TP regimen alone.

PMID- 22969863
TI  - Osteogenic differences in cultured rat periosteal cells under hypoxic and normal
      conditions.
AB  - The aim of the present study was to investigate the osteogenic capability of rat
      calvarial periosteal cells in hypoxic conditions in vitro. Periosteum was
      obtained from the calvarial bone of Sprague-Dawley rats. Following primary tissue
      culture, subcultured cells were used in hypoxic or normal conditions. On days 1,
      2, 3 and 4 following the cell culture, cell proliferation and mRNA and protein
      expression levels were evaluated. No significant difference in the cell
      proliferation rate was found between the normal and hypoxic condition groups. The
      hypoxic condition group exhibited a stronger expression of hypoxia-inducible
      factor (HIF)1alpha, vascular endothelial growth factor (VEGF), Runx2, alkaline
      phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN) and periostin at
      the mRNA level compared to that of the normal condition group. The hypoxic
      condition group also exhibited a stronger expression of HIF1alpha, VEGF, bone
      morphogenetic protein (BMP)2, Runx2, ALP and BSP at the protein level compared to
      that of the normal condition group. In conclusion, periosteal cells cultured in
      hypoxic conditions demonstrated activated osteogenic capability in vitro.

PMID- 22969864
TI  - Cryotherapy is associated with improved clinical outcomes of sorafenib for the
      treatment of advanced hepatocellular carcinoma.
AB  - Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma
      (HCC), but with limited efficacy. The present study aimed to assess the safety
      and efficacy of sorafenib combined with cryotherapy (cryoRx) for the treatment of
      advanced HCC. A total of 104 patients met the following criteria: advanced HCC
      without distant metastasis, presence of portal vein thrombosis, Child-Pugh class
      A or B and life expectancy of at least 12 weeks. All patients were randomly
      assigned to sorafenib and cryoRx (n=52) or sorafenib-alone (n=52) treatment
      groups. The primary end-point of the study was overall survival (OS). The
      secondary end-points included time to progression (TTP) and tolerability.
      Microvessel density (MVD) was assessed following immunostaining for CD34. In a
      median of 10.5 (4-26) months follow-up, the median OS was 12.5 months (95% CI
      10.6-16.4) in the combination therapy vs. 8.6 months (7.3-10.4) in the sorafenib
      alone (P=0.01) group. The median TTP was 9.5 months (8.4-13.5) in the combination
      therapy vs. 5.3 months (3.8-6.9) in the sorafenib alone (P=0.02) group. CryoRx
      was an independent factor associated with improved clinical outcomes of sorafenib
      for the treatment of advanced HCC. Patients with low intratumoral MVD receiving
      the combination therapy exhibited a significantly longer median TTP and OS
      compared to those receiving sorafenib. High intratumoral MVD was an independent
      predictor of poor responses to sorafenib for advanced HCC. Compared with previous
      reports of sorafenib-related adverse drug reactions (ADRs), cryoRx did not
      further increase the frequency and degree of sorafenib-related ADRs. In
      conclusion, compared to sorafenib alone, the addition of cryoRx to sorafenib
      significantly improves the clinical outcomes of sorafenib for the treatment of
      advanced HCC with acceptable tolerance and similar safety profiles as previously
      reported. High intratumoral MVD is predictive of poor responses to sorafenib in
      advanced HCC patients.

PMID- 22969865
TI  - Knockdown of vascular endothelial cell growth factor expression sensitizes U251
      glioma cells to liposomal paclitaxel and radiation treatment in vitro.
AB  - Glioblastoma is the most aggressive malignancy of the human brain, accounting for
      40% of all primary malignant brain tumors. However, there is no effective
      treatment for this disease. This study was designed to develop anti-vascular
      endothelial growth factor (VEGF) as a novel adjuvant therapy for glioblastoma. A
      VEGF shRNA vector was constructed to silence VEGF expression in U251 glioma cells
      and these cells were treated with various concentrations of liposomal paclitaxel,
      6 Gy radiation or liposomal paclitaxel plus radiation. The data demonstrated that
      the VEGF shRNA vector significantly knocked down VEGF expression, which
      synergistically sensitized U251 glioma cells to liposomal paclitaxel, radiation
      or liposomal paclitaxel plus radiation treatment in terms of cell viability,
      apoptosis, colony formation and morphological changes. Future studies are
      required to evaluate these effects in vivo.

PMID- 22969866
TI  - Antitumor effect of microbubbles enhanced by low frequency ultrasound cavitation
      on prostate carcinoma xenografts in nude mice.
AB  - The aim of this study was to investigate the antitumor effect induced by low
      frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection
      of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145
      prostate tumors were percutaneously implanted in 40 nude mice, which were
      randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups.
      The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm(2) US radiation
      and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were
      only treated with US radiation and injection of Mbs, respectively. Tumors were
      measured with sonography, and the ratio of antitumor growth was calculated. The
      mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were
      observed pathologically using light microscopy and transmission electron
      microscopy. Microvessel density and the average optical density of vascular
      endothelial growth factor were compared among groups by immunohistochemistry. The
      average gross tumor volume of the US+Mbs group was significantly reduced compared
      with the other groups following treatment (P<0.05). The ratio of the antitumor
      growth in the US+Mbs group was significantly greater than that of the US and Mbs
      group (P<0.05). Histological examination showed signs of tumor cell injury in the
      US+Mbs group. Examination by electron microscopy revealed vessel injury in the
      endothelium in the tumors treated with US+Mbs. Microvessel density and the
      average optical density of vascular endothelial growth factor in the US+Mbs group
      were significantly less than that of other groups (P<0.05). In conclusion, low
      frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the
      growth of human prostate carcinoma xenografts in nude mice, and the effect is
      likely realized through microvessel destruction caused by cavitation.

PMID- 22969867
TI  - Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in
      depressed rats: Involvement of reduction of connexin 43.
AB  - Connexin 43 (Cx43) has been reported to contribute to the occurrence of
      ventricular arrhythmias during myocardial ischemia (MI). In this study, we
      investigated the expression of Cx43 and the incidences of ventricular
      tachyarrhythmias [i.e., ventricular tachycardia (VT) and ventricular fibrillation
      (VF)] during acute MI in chronic mild stress (CMS) in rats. Male Sprague-Dawley
      (SD) control and CMS rats were assigned into a sham operation (SO) group and a MI
      group. Ventricular tachyarrhythmias were assessed and Cx43 protein expression was
      measured by Western blotting. During 30-min ischemia, the incidences of VT (7/12,
      58.3%) and VF (5/12, 41.7%) in the CMS-MI group were significantly decreased
      compared with those in the control-MI group (12/12, 100.0% and 11/12, 91.7%;
      P<0.05). The amount of total Cx43 of the CMS-SO group was significantly decreased
      to approximately 50% compared with that of the control-SO group (P<0.05). The 30
      min ischemia did not result in a significant change in the amount of total Cx43
      (total Cx43 is defined as the non-phosphorylated Cx43 and phosphorylated Cx43)
      compared to that of the SO group in CMS rats (P>0.05). The amount of non
      phosphorylated Cx43 in the CMS-MI group was markedly increased compared to that
      of the CMS-SO group (P<0.05), suggesting that the relative amount of
      phosphorylated Cx43 was significantly decreased in CMS rats. The gap junctional
      permeability in the CMS-MI group (50.4+/-4.9%) was significantly decreased
      compared with the normal non-ischemic value in the CMS-SO group (100%). The
      present study suggested that the incidence of ischemia-induced ventricular
      tachyarrhythmias was markedly increased in depressed rats, which may be
      associated with the reduction of Cx43 protein expression in the ventricle of
      depressed rats.

PMID- 22969868
TI  - Subcellular location of antitumor tripeptide-tyroserleutide in human
      hepatocellular carcinoma cells.
AB  - Tyroserleutide (YSL) is a tripeptide compound that exhibits potent antitumor
      activity in human tumor xenografts and tumor cell lines. However, the target of
      YSL on which it exerts its antitumor activity has yet to be identified.
      Therefore, our study aimed to investigate the subcellular location of YSL in BEL
      7402 human hepatocellular carcinoma cells. Using methods of fluorescent tracing
      and confocal colocalization, we provide evidence that when BEL-7402 cells are
      treated with YSL, YSL is distributed in the cytoplasm and colocalized with the
      mitochondria of cancer cells. Furthermore, we observed the effect of YSL on the
      isolated mitochondria. Using fluorescence spectrophotometry to monitor the
      Deltapsi collapse of mitochondria isolated from BEL-7402 cells by reversion of
      the quenching of tetramethylrhodamine methyl ester (TMRM), we found that the
      isolated mitochondria reversed the quenching of the fluorescence in the solution
      containing TMRM and YSL. This indicates that YSL decreases the Deltapsi of the
      isolated mitochondria. Another photometry method was used to observe the effect
      on mitochondrial swelling when YSL acted directly on the isolated mitochondria.
      We reveal that YSL directly causes mitochondrial swelling in 60 min. In
      conclusion, this study encloses a preliminary facet of the pharmacological target
      of YSL, and we speculate that YSL may act directly on the mitochondria to exert
      its antitumor activity.

PMID- 22969869
TI  - Two IL28B polymorphisms are associated with the treatment response of different
      genotypes of hepatitis C in different racial populations: A meta-analysis.
AB  - The purpose of this present meta-analysis is to provide an accurate estimation of
      the association between two IL28B polymorphisms (rs8099917 and rs12979860) and
      sustained virological response (SVR) to standard treatment of patients of
      different racial descent infected with different genotypes of hepatitis C virus
      (HCV), and also to investigate the possible factors in the IL28B gene that
      contribute to the different SVR rates of patients with different subtypes of HCV
      infection across different populations. The electronic database PubMed was
      searched. Asian patients with a common homozygote (TT vs. TG/GG, OR=3.17; CC vs.
      CT/TT, OR=3.75) attained a higher rate of SVR, and a similar result was observed
      in European patients (TT vs. TG/GG, OR=1.74; CC vs. CT/TT, OR=2.50). Furthermore,
      HCV1-infected patients with a common homozygote (TT vs. TG/GG, OR=2.95; CC vs.
      CT/TT, OR=4.34) appeared to have a higher SVR rate than those with HCV2/3 (TT vs.
      TG/GG, OR=1.56; CC vs. CT/TT, OR=1.37). The frequency of the common homozygote in
      Asian patients was high, followed by European patients and African patients. In
      all, Asian patients attained a higher SVR rate than European patients (P<0.05).
      Patients with HCV1 infection had a lower SVR rate than those with HCV2/3
      infection (P<0.001). Our results suggest that both the common allele frequency
      and racial descent itself contribute to the difference in SVR rates across
      different population groups, and the common allele frequency may partly elucidate
      the different SVR rates in patients with different genotypes of HCV.

PMID- 22969870
TI  - Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without
      EGFR-activating mutations, but similar efficacy in patients with EGFR-activating
      mutations.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an
      effective treatment for advanced non-small cell lung cancer. The objective of the
      present study was to compare the efficacy of gefitinib and erlotinib in patients
      with pulmonary adenocarcinoma, whose tumor EGFR mutation status was known.
      Pulmonary adenocarcinoma patients who began receiving gefitinib or erlotinib
      treatment from January 2005 to December 2010, and whose tumor EGFR mutation
      status had been determined, were included. Clinical data, type of treatment
      response and survival time data were collected. Of the 224 patients enrolled, 124
      received gefitinib treatment and 100 received erlotinib treatment. Of these
      patients, 146 individuals had tumors with EGFR-activating mutations (exon 19
      deletions and/point mutation of L858R in exon 21) and 78 did not. There was no
      difference in treatment response whether or not the patients had tumors with EGFR
      activating mutations at the time they received gefitinib or erlotinib treatment.
      The median progression-free survival (PFS) of the gefitinib and erlotinib groups
      was 7.6 and 7.9 months, respectively (p=0.4731). PFS was significantly longer for
      patients without EGFR-activating mutations who received erlotinib treatment
      (n=48; median, 4.5 months) than for those who received gefitinib treatment (n=30;
      median, 2.3 months), with a hazard ratio of 0.58 (95% CI, 0.35-0.96; p=0.0339).
      Patients whose tumors had EGFR-activating mutations displayed no difference in
      PFS with either gefitinib (n=94; median, 10.5 months) or erlotinib treatment
      (n=52; median, 10.4 months). In conclusion, PFS showed no difference with either
      agent in patients whose tumors had EGFR-activating mutations, but was
      significantly longer in patients whose tumors did not have EGFR-activating
      mutations when receiving erlotinib treatment.

PMID- 22969871
TI  - Microwave coagulation using a perfusion microwave electrode: Preliminary
      experimental study using ex vivo and in vivo liver.
AB  - To assess the coagulation capability of a perfusion microwave electrode (PME) as
      a key component of microwave coagulation therapy, a preliminary experimental
      study was performed using ex vivo and in vivo livers. For a microwave electrode,
      a PME was employed. Using a PME, saline was passed through the electrode and
      injected continuously into the target tissue. Using an ex vivo bovine liver, the
      range of tissue coagulation was measured for various volumes of infused saline
      and microwave outputs. Using an in vivo porcine liver, the efficiency of
      coagulation by a PME was compared with that of radiofrequency ablation (RFA)
      using a cool-tip needle. In an ex vivo bovine liver, the range of tissue
      coagulation increased as the flow rate of saline increased. In the in vivo
      porcine liver, the range of coagulation was similar to that found in the ex vivo
      bovine liver. With a PME under conditions of a microwave output of 80 W, a flow
      rate of 3 ml/min and irradiation time of 5 min, the range of coagulation was
      44.8+/-2.8 mm [maximum vertical diameter: (a)] x 31.2+/-2.4 mm [maximum
      transverse diameter: (b)]. The range of RFA (cool-tip needle) at 12 min was
      46.0+/-2.0 mm (a) x 30.2+/-2.0 mm (b). With only 5 min of microwave irradiation,
      the use of a PME enabled induction of the same range of coagulation that was
      obtainable by RFA for 12 min. In comparison with microwave coagulation without
      saline infusion, the use of a PME made it possible to extend the range of tissue
      coagulation to a range equal to that of RFA in a short time. Microwave
      coagulation using a PME may be one of the suitable tissue coagulation systems for
      local ablation treatment.

PMID- 22969872
TI  - Monthly intravesical bacillus Calmette-Guerin maintenance therapy for non-muscle
      invasive bladder cancer: 10-year experience in a single institute.
AB  - Intravesical bacillus Calmette-Guerin (BCG) therapy is the standard prophylaxis
      for recurrence of non-muscle-invasive bladder cancer (NMIBC). The aim of this
      study was to confirm the recurrence- and progression-preventing efficacy and
      safety of 12 times monthly BCG maintenance therapy for NMIBC. This study included
      126 patients diagnosed with Ta, T1 and carcinoma in situ bladder cancer between
      January 2000 and December 2009. Thirty-four patients in the no maintenance group
      received a single 6-week course of intravesical immunotherapy after transurethral
      resection of the bladder tumor (TUR-BT). Ninety-two patients in the maintenance
      group received a 12-month course after a single 6-week course of intravesical
      immunotherapy. Recurrence, progression and side effects were assessed. End-points
      were recurrence-free survival (RFS), progression-free survival (PFS) and disease
      specific survival (DSS). The estimated median RFS was 87 months (95% CI 53.0
      120.9) in the maintenance group and 48 months (95% CI 0-96.8) in the no
      maintenance group (log-rank test; P=0.002). The 2-year cumulative RFS rates were
      77.3% in the maintenance group and 52.6% in the no maintenance group. Median PFS
      and DSS were not estimable in both groups. The 2-year cumulative PFS rates were
      91.1% in the maintenance group and 80.5% in the no maintenance group (log-rank
      test; P=0.178). The 2-year cumulative DSS rates were 97.7% in the maintenance
      group and 91.4% in the no maintenance group (log-rank test; P=0.111). The overall
      side effects were 40.2% in the maintenance group and 44.1% in the no maintenance
      group. Monthly maintenance immunotherapy appears to increase RFS rates in high
      risk NMIBC. Further study is required to evaluate the efficacy of BCG monthly
      maintenence for increasing the PFS rate.

PMID- 22969873
TI  - Concurrent use of Sr-89 chloride with zoledronic acid is safe and effective for
      breast cancer patients with painful bone metastases.
AB  - Our aim in this study was to examine the safety and efficacy of the concurrent
      use of the radiopharmaceutical strontium-89 (Sr-89) chloride with zoledronic acid
      in standard anticancer therapy for breast cancer patients with painful multifocal
      bone metastases. The study comprised 16 breast cancer patients with painful
      multifocal bone metastases detected by bone scintigraphy, computed tomography or
      magnetic resonance imaging. All patients were treated with Sr-89 and zoledronic
      acid concurrently between March 2007 and February 2011 as part of a standard
      therapeutic regimen comprising chemotherapy, endocrine therapy, molecular
      targeting therapy and targeted radiotherapy. Sr-89 was administered intravenously
      at 2 MBq/kg to a maximum of 141 MBq per person. Safety was evaluated according to
      myelotoxicity as measured by the Common Terminology Criteria for Adverse Events
      (v3.0). To assess treatment efficacy, we monitored changes in analgesic drug
      dosages. Furthermore, bremsstrahlung imaging after the administration of Sr-89
      was utilized to examine the relationship between the accumulation of Sr-89 in
      metastatic sites and treatment efficacy. Based on the results, a total of 14 out
      of 16 patients (88%) reported bone pain relief, indicating a high efficacy of Sr
      89 combined with zoledronic acid. In responsive cases, a strong uptake of Sr-89
      was observed on bremsstrahlung imaging at the same sites indicated by (99m)Tc
      bone scintigraphy. Moreover, severe myelosuppression (> grade 3) was not
      observed, and adverse events were tolerable. In conclusion, the use of Sr-89 with
      zoledronic acid in breast cancer patients with painful bone metastases was safe
      and effective when administered concurrently with other standard therapies. In
      the future, the treatment with Sr-89 at the early stage should be considered, and
      a large-scale clinical study should be conducted.

PMID- 22969875
TI  - Investigation of FJ 194940.1 gene alternative splicing in colon cancer and its
      association with clinicopathological parameters.
AB  - Colorectal cancer (CRC) is one of the most frequent neoplasms and is responsible
      for the second highest mortality rate of all cancers in the more developed
      regions of the world. The molecular mechanisms of CRC are relatively well
      characterized and are correlated to the accumulation of genetic mutations and
      certain patterns of gene expression/over-expression. There are a number of
      possible molecular factors involved in CRC progression in the aforementioned
      pathways, which are as yet not well described. One of these factors appears to be
      the gene FJ 194940.1, previously termed P65. FJ 194940.1 consists of 6 exons and
      probably undergoes alternative splicing in malignant tissues. In this study,
      tissue samples from 102 patients with colon cancer were investigated to confirm
      alternative splicing and to correlate results obtained with clinicopathological
      parameters. A total of 18 splice variants, which arise from various combinations
      of 4 exons (II, III, IV and V) and exon-exon junctions between exons 1 and 2
      (I/II); 2 and 3 (II/III); 3 and 4 (III/IV), as well as 4 and 5 (IV/V), were
      found. For statistical analysis the full length transcript was divided into parts
      A and B. Part A consisted of exons II and III, as well as I/II and II/III exon
      exon junctions, whereas part B comprised exons IV and V, as well as III/IV and
      IV/V exon-exon junctions. The expression of part B of the FJ 194940.1 gene
      transcript is correlated with well-differentiated (G1) and moderately
      differentiated cases (G2). Lymphocytic tumor infiltration, a good prognostic
      factor in CRC, was significantly correlated to the presence of all elements in
      part A of the FJ 194940.1 gene transcript. Patients who had all elements in part
      A of the transcript survived for a shorter duration. Investigation of the FJ
      194940.1 gene revealed that the gene had undergone alternative splicing. However,
      the role of its transcripts and potential proteins should be examined in detail.

PMID- 22969874
TI  - Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human
      keratinocytes, the role of PLC-gamma and potential clinical implications.
AB  - Interleukin (IL)-8 is a pro-inflammatory cytokine that has a direct effect on
      immune cells, including polymorphonuclear cells. Keratinocytes are a rich source
      of IL-8. However, there is little knowledge on the role of IL-8 in clinical wound
      healing and the direct biological effect of IL-8 on keratinocytes. In this study,
      the effect of recombinant human IL-8 (rhIL-8) on migration and adhesion was
      tested using HaCaT keratinocytes as a cell model. The cell functions were
      evaluated using impedance cell sensing. The expression of IL-8 receptor (IL-8R)
      transcripts in human skin and wounds (acute and chronic) was assessed using real
      time transcript analysis. rhIL-8 significantly increased the migration of
      keratinocytes (3.5+/-0.3 for cells treated with IL-8 vs. 2.7+/-0.6 for controls;
      p=0.029). It is interesting to note that treatment of keratinocytes with IL-8
      resulted in a marked shift in the responsive frequencies. IL-8 only resulted in a
      marginal increase in cell adhesion, which was particularly noticeable at high
      frequencies. The PLC-gamma inhibitor completely eradicated the action of IL-8 on
      the migration of HaCaT cells. Using real time PCR, it was found that chronic
      wounds had significantly lower levels of the B form of the IL-8R (IL-8RB)
      (p=0.045) and marginally lower levels of the A form, IL-8RA, in comparison with
      acute wounds. Therefore, IL-8 has a direct and profound stimulatory effect on the
      migration of human keratinocytes, which is likely to occur via the PLC-gamma
      pathway. Together with a reduced level of IL-8Rs in difficult-healing wounds, IL
      8 has a clear prognostic and therapeutic value in wound healing.

PMID- 22969876
TI  - Multidetector-computed tomography attenuation values between the tumor and aortic
      wall in response to induction therapy for esophageal cancer and its predictive
      value for aortic invasion.
AB  - The objective of this study was to evaluate the multidetector computed tomography
      (MDCT) attenuation value between the tumor and aorta in response to the induction
      therapy for esophageal cancer. In advanced esophageal cancer, the main reason for
      unresectability is the local invasion of the tumor into the aorta or trachea.
      Despite remarkable advances in diagnostic modalities, pre-operative assessment of
      pathological response and local tumor extent in esophageal cancer remains
      difficult. MDCT attenuation values between the tumor and aorta, and the contact
      angle of the tumor to the aorta (Picus' angle) were retrospectively evaluated in
      patients with esophageal cancer who underwent induction therapy in terms of
      predicting the pathological response, aortic invasion and prognosis of esophageal
      cancer. The induction therapy may increase the tumor-to-aorta distance and
      decrease the maximum tumor size and Picus' angle. When the tumor-to-aorta cut-off
      value was set at <1.3 mm, the accuracy of this distance for aortic invasion was
      94.6%. In terms of this distance, 14 out of 19 patients with a tumor-to-aorta
      distance of <1.3 mm prior to the induction therapy had a distance of >1.3 mm
      following therapy and underwent curative resection. The assessment of the MDCT
      attenuation value between the esophageal tumor and the aorta is simple and
      objectively assesses the response to the induction therapy and aortic invasion in
      esophageal cancer. This method should be applied to predict the response to the
      induction therapy and to prevent unnecessary surgery in patients with tumors
      involving the aorta.

PMID- 22969877
TI  - Effects of quercetin on apoptosis, NF-kappaB and NOS gene expression in renal
      ischemia/reperfusion injury.
AB  - The aim of this study was to investigate the effects of quercetin on nitric oxide
      synthase (NOS), nuclear factor-kappaB (NF-kappaB) and apoptosis in renal
      ischemia/reperfusion (I/R) injury in rats. A total of 42 Sprague-Dawley rats were
      divided into three groups. The control, I/R and I/R+quercetin (I/R+Q) groups were
      treated with quercetin (50 mg/kg intraperitoneal) 1 h prior to the induction of
      ischemia. Tissue malondialdehyde (MDA) and glutathione (GSH) levels were
      determined by high-performance liquid chromatography (HPLC). p53, endothelial NOS
      (eNOS) and NF-kappaB expression were assessed immunohistochemically, and
      apoptosis assesment was performed using terminal deoxynucleotidyl transferase
      dUTP nick end-labeling (TUNEL) assay. The mRNA levels of inducible NOS (iNOS) in
      renal tissue were determined by real-time polymerase chain reaction (RT-PCR). MDA
      levels were significantly decreased in the quercetin group compared to the I/R
      group. However, GSH levels were significantly increased with quercetin treatment
      in the I/R group. Histological results, the number of apoptotic and p53-positive
      cells, NF-kappaB and eNOS expression levels were significantly decreased in the
      quercetin treatment group compared to the I/R group. iNOS gene expression
      increased in the I/R group, but no significant difference was found between the
      I/R and quercetin treatment groups. Therefore, quercetin not only has antioxidant
      and anti-apoptotic activities, but also has an inhibitory effect on eNOS and NF
      kappaB for renal tissue protection during I/R injury in rats. Therefore,
      quercetin may be a promising renoprotective therapeutic agent.

PMID- 22969878
TI  - Increase of the therapeutic effect on non-small-cell lung cancer cells with
      combination treatment of shRNA against Cyclin D1 and Bcl-xL in vitro.
AB  - Overexpression of Cyclin D1 and Bcl-xL proteins has often been found in non-small
      cell lung cancer (NSCLC). These two genes may play a significant role in
      tumorigenesis. However, the combined inhibition of the two genes in vitro is
      unclear in NSCLC. In this study, the effect of a combined intervention on Cyclin
      D1 and Bcl-xL in NSCLC is assessed and discussed. Three recombinant plasmids that
      expressed a cytomegalovirus (CMV) promoter-driven micro30 short hairpin RNA
      (shRNA) targeting the Cyclin D1 gene (Cyclin D1 shRNA), the Bcl-xL gene (Bcl-xL
      shRNA) and a combination of the two genes (Cyclin D1-Bcl-xL shRNA), based on the
      plasmid pcDNA6.2-GW/EmGFP-miR, were constructed. The cell lines A549 and NCI-H441
      were divided into four groups; blank control (untreated cells), Cyclin D1 shRNA,
      Bcl-xL shRNA and Cyclin D1-Bcl-xL shRNA (transfected cells), respectively. The
      expression of mRNA and protein of Cyclin D1 or Bcl-xL was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting,
      respectively. The apoptosis and proliferation of the two cell lines were
      evaluated by dimethylthiazol-diphenyltetrazolium bromide (MTT), cell count and
      flow cytometry. The recombinant plasmid sufficiently mediated the RNA
      interference (RNAi) effects in A549 and NCI-H441 cells. The expression levels of
      mRNA and protein of Cyclin D1 or Bcl-xL in the three intervention groups were
      significantly reduced compared to the untreated cells (P<0.05). No statistical
      differences were found among the combined shRNAs and single shRNA regarding
      Cyclin D1 or Bcl-xL, respectively (P>0.05). In the assessment of proliferation
      and apoptosis, it was found that in all three intervention groups there was
      significant inhibition of cell proliferation and promotion of cell apoptosis
      compared with the untreated cells (P<0.05). Furthermore, the combined
      interference of the two genes was more effective than either single interference
      (P<0.05). Our results suggested that the combined targeting of Cyclin D1 and Bcl
      xL genes has potential for NSCLC investigation, providing increased efficacy over
      Cyclin D1 or Bcl-xL inhibition alone.

PMID- 22969879
TI  - Association between cytochrome P450 promoter polymorphisms and ischemic stroke.
AB  - The human cytochrome P450 (CYP) superfamily includes at least 57 genes that
      encode enzymes with diverse metabolic and biosynthetic functions. This study was
      conducted in order to investigate the associations between polymorphisms in CYP
      superfamily genes (CYP11B2, CYP17A1, CYP2B6, CYP2C9, CYP2E1 and CYP7A1) and
      ischemic stroke (IS). Six single nucleotide polymorphisms (SNPs) of CYP
      superfamily genes were selected and genotyped by direct sequencing in 121
      patients with IS and 321 control subjects. The genetic data were analyzed using
      SNPStats and SPSS 18.0. Multiple logistic regression models (codominant 1,
      codominant 2, dominant, recessive and log-additive) were used to evaluate odds
      ratios (ORs), 95% confidence intervals (CIs) and p-values. The rs179998 SNP of
      CYP11B2 was significantly associated with IS (p=0.0336 in a log-additive model).
      The rs3813867 SNP of CYP2E1 was significantly associated with smoking in IS
      (p=0.0336 in a log-additive model). The rs1799998 SNP of CYP11B2 and rs3808607 of
      CYP7A1 were related to diabetes mellitus in IS (p<0.05). CYP11B2, CYP2E1 and
      CYP7A1 SNPs were associated with IS in the population studied. Further study is
      required to confirm these associations and to determine their biological
      significance.

PMID- 22969880
TI  - Steady and fluctuant methods of inhibition of acetylcholinesterase differentially
      regulate neurotrophic factors in the hippocampus of juvenile mice.
AB  - The present study was designed to evaluate the effects of steady and fluctuant
      inhibition of acetylcholinesterase (AChE) activity on neurotrophic factors in the
      hippocampus of juvenile mice. Steady inhibition of AChE activity was induced by
      an intramuscular injection of huperizine A (HupA) sustained-release microspheres.
      Fluctuant inhibition of AChE activity was induced by an intragastric
      administration of HupA tablets. Six days after cessation of steady AChE
      inhibition, there was a significant increase in the levels of brain-derived
      neurotrophic factor (BDNF) and nerve growth factor (NGF). In contrast, fluctuant
      AChE inhibition had no effect on BDNF and NGF levels. Additionally, neither
      steady nor fluctuant inhibition of AChE activity altered the choline
      acetyltransferase activity or spatial learning in juvenile mice. These findings
      indicate that steady and fluctuant methods of inhibition of AChE have different
      effects on the levels of BDNF and NGF in the hippocampus. In addition, the
      effects of AChE inhibitors may not improve learning in normal juvenile animals.

PMID- 22969881
TI  - Use of a novel sonosensitizer in sonodynamic therapy of U251 glioma cells in
      vitro.
AB  - The aim of the present study was to investigate the effect of ZnPcS(2)P(2)
      meditated sonodynamic therapy (SDT) on U251 human glioma cells and to identify
      its underlying biological mechanism. The growth inhibition rate was determined by
      MTT assay. The apoptotic rate was examined by flow cytometry. Fine structures
      were observed with transmission electron microscopy (TEM). Generation of reactive
      oxygen species (ROS) was detected spectrophotometrically. Caspase-3, -8 and -9
      expression was detected by Western blot analysis. The growth inhibition rate of
      U251 human glioma cells indicated that ZnPcS(2)P(2)-meditated SDT had a better
      growth inhibition rate of tumor cells at a concentration of 5.0 MUg/ml
      ZnPcS(2)P(2), at a 4-h incubation time with ZnPcS(2)P(2), and at 6 h re
      incubation following SDT. At 6 h after SDT, the growth inhibition rate of cells
      was significantly higher compared to other groups, apoptosis could be detected in
      SDT by flow cytometry. TEM examination revealed morphological features of
      apoptosis or necrosis. Furthermore, caspase-3, -8 and -9 expression following SDT
      was found to be increased by Western blot analysis. Finally, generation of ROS in
      cells was also elevated. In conclusion, ZnPcS(2)P(2)-SDT is capable of inducing
      U251 cell apoptosis or necrosis and has satisfying antitumor effects. The
      mechanism of ZnPcS(2)P(2)-meditated SDT involves ROS generation in U251 cells,
      which initiates subsequent apoptosis through the mitochondrial and death receptor
      pathways.

PMID- 22969882
TI  - Magnetic fluid hyperthermia induced by radiofrequency capacitive field for the
      treatment of transplanted subcutaneous tumors in rats.
AB  - Magnetic fluid hyperthermia (MFH) induced by a magnetic field has become a new
      heating technology for the treatment of malignant tumors due to its ability to
      heat the tumor tissue precisely and properly, and due to its significant
      therapeutic effects. In this study, MFH induced by radiofrequency capacitive
      field (RCF) for the treatment of transplanted subcutaneous tumors in rats, was
      investigated. A total of 50 rats bearing subcutaneous tumors were randomly
      divided into five groups, including i) a pseudo-treatment (PT) control group, ii)
      magnetic fluid (MF) group, iii) pure hyperthermia (PH) group, iv) magnetic fluid
      hyperthermia 1 (MFH1) group, and v) magnetic fluid hyperthermia 2 (MFH2) group.
      Tumors were irradiated for 30 min in the MFH1 group 24 h following injection of
      MF. Tumors were irradiated for 30 min in the MFH2 group 24 h following injection
      of MF, and irradiation was repeated for 30 min 72 h following injection of MF.
      Tumor volumes, tumor volume inhibition ratios and survival times in the rat model
      were examined. Temperatures of tumor cores and rims both rapidly reached the
      desired temperature (~50 degrees C) for tumor treatment within 5 to 10 min in the
      MFH1 and MFH2 groups, and we maintained this temperature level by manually
      adjusting the output power (70-130 W). Tumor volumes of the MFH1 and MFH2 groups
      were reduced compared to those of the PT, MF and PH groups. The inhibitory effect
      on tumor growth in the MFH2 group (91.57%) was higher compared to that in the
      MFH1 group (85.21%) and the other groups. The survival time of the MFH2 group
      (51.62+/-2.28 days) and MFH1 group (43.10+/-1.57 days) was increased compared to
      that of the PH, MF and PT groups. The results obtained show that MFH induced by
      RCF may serve as a potential and promising method for the treatment of tumors.

PMID- 22969883
TI  - Characterization of diethylnitrosamine-induced liver carcinogenesis in Syrian
      golden hamsters.
AB  - The aim of this study was to characterize hepatocarcinogenesis in
      diethylnitrosamine (DEN)-treated hamsters. Syrian golden hamsters (n=36) were
      administered DEN by hypodermic injection and addition to drinking water.
      Morphological analyses, including light microscopy and immunohistochemistry of
      alpha-fetal protein (AFP), were performed on liver and lung tissues. Primary cell
      culture and tumor transplantation were carried out to evaluate the potential
      application in hepatocellular carcinoma (HCC) research. From 25 to 50 weeks of
      treatment, liver tumors, including macronodular HCC and ascites, were found in
      one-third (4/12) of the animals treated with DEN. HCC was characterized by poor
      differentiation, frequent mitosis, AFP reaction, vessel invasion and potential
      application in primary cell culture and xenotransplantation. Pre-neoplastic
      lesions were hyperplastic nodules comprised of clear cells, bile duct
      proliferation, fatty metamorphosis and multilocular cysts. The DEN-treated
      hamsters also showed lung tumors consisting of AFP-negative, well-differentiated
      neoplastic cells. Characterization of DEN-induced HCC in hamsters provides
      insights into human hepatocarcinogenesis. This animal model has potential
      applications in HCC research.

PMID- 22969885
TI  - Improved radiosensitizing effect of the combination of etanidazole and paclitaxel
      for hepatocellular carcinoma in vivo.
AB  - Hepatocellular carcinoma (HCC) is one of the most critical global health issues.
      Potential curative therapies, including surgical resection, are offered to only a
      limited number of patients. Therefore, new and effective treatment strategies are
      required. Recently, radiotherapy with hypoxic radiosensitizers has shown promise
      in cancer therapy. Our previous study demonstrated that radiosensitization
      produced by etanidazole and paclitaxel was additive in vitro. This study was
      carried out to determine the synergistic effect of the two drugs in murine HCC
      H22 cell xenograft-bearing BALB/c mice in vivo. The morphology of the
      transplanted tumors was observed. The drug content in the blood and tumors of
      mice was measured by high-performance liquid chromatography. The radiosensitizing
      effect on H22 cell xenograft-bearing mice was evaluated in terms of tumor growth
      inhibition and survival. Expression of hypoxia inducible factor-1alpha (HIF
      1alpha) was studied using immunohistochemistry. The morphological consequences on
      the H22 xenografts were consistent with the pathological characteristics of HCC.
      There was no significant difference in drug content in the blood and tumors
      between single drug and combination administration. The combination of the two
      drugs improved the radiosensitizing effect in vivo compared to single drug
      administration in an animal model. The changes in HIF-1alpha expression
      indirectly verified the above-mentioned results. This study may provide a new
      combination of radiosensitizers for HCC radiotherapy.

PMID- 22969884
TI  - Repair of meniscal defect using an induced myoblast-loaded polyglycolic acid mesh
      in a canine model.
AB  - Defects of the meniscus greatly alter knee function and predispose the joint to
      degenerative changes. The purpose of this study was to test a recently developed
      cell-scaffold combination for the repair of a critical-size defect in the canine
      medial meniscus. A bilateral, complete resection of the anterior horn of the
      medial meniscus was performed in 18 Beagle canines. A PLGA scaffold was implanted
      into the defect of one knee of 6 canines and the contralateral defect was left
      untreated. Scaffolds loaded with autologous myoblasts and cultured in a
      chondrogenic medium for 14 days were implanted in a second series of 12 canines.
      Empty scaffolds were implanted in the contralateral knees. Menisci were harvested
      at 12 weeks. Untreated defects had a muted fibrous healing response. Defects
      treated with cell-free implants also showed predominantly fibrous tissue, whereas
      fibrocartilage was present in several scaffolds. The thickness of the repair
      tissue after treatment with cell-free scaffolds was significantly greater
      compared to the controls (p<0.05). Pre-cultured implants integrated with the host
      tissue, and 9 of 12 contained meniscus-like fibrocartilage when compared to 2 of
      the 12 controls (p<0.05). The thickness of the pre-cultured implant repair tissue
      was greater compared to the controls (p<0.05). This study demonstrates the repair
      of a critical size meniscal defect using a stem cell and scaffold-based tissue
      engineering approach.

PMID- 22969886
TI  - Long-term follow-up of localized, primary gastric diffuse large B-cell lymphoma
      treated with rituximab and CHOP.
AB  - The addition of rituximab to cyclophosphamide, doxorubicin, vincristine and
      prednisone [CHOP (i.e., R-CHOP)] is considered to be the standard regimen for
      treating localized, primary gastric diffuse large B-cell lymphoma (PG-DLBCL).
      However, few studies have reported the long-term efficacy of R-CHOP therapy in
      the management of localized PG-DLBCL. In the present study, we performed a
      retrospective analysis of 11 patients with localized PG-DLBCL, who were treated
      with R-CHOP at Nihon University Itabashi Hospital and Kasukabe Municipal Hospital
      (Japan) from 2001 to 2008. Limited stage cancer was defined as stage I/II
      according to the Lugano staging system for gastrointestinal (GI) lymphomas. The
      relative dose intensity (RDI) of CHOP therapy was calculated for each patient.
      The median age of the patients was 68 years (range, 48-82). Gastralgia and anemia
      were common symptoms at initial presentation. All patients except 1 received 6
      cycles of R-CHOP treatment without consolidative radiation therapy or prior
      surgery. RDI was maintained at over 80% in 9 out of 11 patients. All patients
      achieved complete remission and the estimated overall survival with a median
      follow-up of 54 months (range, 39-103) was 100%, without relapse or significant
      GI adverse effects, such as perforation or bleeding during R-CHOP treatment. No
      long-term adverse effects of rituximab were recorded during the observation
      period. Helicobacter pylori infection was diagnosed in 72.7% (8 cases) of the
      patients, but was eradicated in a limited number of patients. Our data suggest
      the feasibility and effectiveness of the addition of rituximab to conventional
      CHOP therapy in the management of localized PG-DLBCL.

PMID- 22969887
TI  - Association of SLC38A4 and system A with abnormal fetal birth weight.
AB  - In this study, we aimed to explore the correlation between solute carrier family
      38 member 4 (SLC38A4) and system A activity in human placentas from pregnancies
      with abnormal fetal birth weight. We collected placentas from consenting women
      immediately after their full-term babies were born, with normal, low birth weight
      or macrosomia, and used real-time PCR and Western blot analysis to detect the
      levels of SLC38A4 mRNA and protein [also known as sodium-coupled neutral amino
      acid transport protein 4 (SNAT4)]. Isotope incorporation assay was applied to
      measure system A activity in the placentas. Compared to the normal birth weight
      (NBW) group, placentas from the fetal macrosomia (FM) group had significantly
      increased levels of SLC38A4 mRNA and SNAT4 (both were increased by almost 2-fold;
      P<0.05), while no significant changes were detected in the placentas from the low
      birth weight (LBW) group. In addition, system A activity in the placentas from
      the FM and LBW groups was significantly different from that in the NBW group
      (1.2+/-0.20, 0.6+/-0.14 vs. 1.0+/-0.18, P<0.05). The data suggest that SNAT4 and
      system A have a strong association with abnormal fetal birth weight and that they
      may play a crucial role in fetal growth and development.

PMID- 22969888
TI  - Dan-Shen-Yin protects the heart against inflammation and oxidative stress induced
      by acute ischemic myocardial injury in rats.
AB  - Dan-Shen-Yin (DSY) is a well-known traditional Chinese formula which is widely
      used in clinical practice for the treatment of coronary heart disease (CHD) and
      has produced a favorable effect in China. The present study was designed to
      examine whether or not acute oral DSY can protect the heart against myocardial
      infarction in acute myocardial ischemic rats. If so, we would then investigate
      the anti-inflammatory and anti-oxidant mechanisms involved. The left anterior
      descending coronary artery was occluded to induce myocardial ischemia in the
      hearts of Sprague-Dawley rats. At the end of the 3-h ischemic period (or 24 h for
      infarction size), we measured the myocardial infarction size, inflammatory
      factors and the activities of anti-oxidative enzymes. DSY reduced the infarction
      size and the serum levels of C-reactive protein, interleukin-6, tumour necrosis
      factor-alpha and malondialdehyde and increased the activities of superoxide
      dismutase and the serum levels of glutathione. The results show that DSY exerts
      significant cardioprotective effects against acute ischemic myocardial injury in
      rats, possibly through its anti-inflammatory and anti-oxidant properties, and may
      thus be used as a potential therapeutic reagent for the treatment of CHD.

PMID- 22969889
TI  - Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric
      cancer cell total RNA carrying the 4-1BBL gene in vitro.
AB  - T cell-mediated antitumor immunity is a cellular immune response that requires
      two signals. The dendritic cell (DC) has been considered as the most efficient
      antigen-presenting cell (APC). It plays essential roles in the induction,
      regulation and maintenance of antitumor immunity in humans. The 4-1BB/4-1BB
      ligand (4-1BBL) pathway plays crucial roles in immune response, tumor immunity
      and autoimmune diseases through transduction of T cell co-stimulatory signals.
      The aim of this study was to generate the preparation protocol for a DC vaccine
      transfected with gastric cancer cell total ribonucleic acid (RNA) carrying the 4
      1 BBL gene in vitro and to investigate its antitumor effects in murine
      forestomach carcinoma (MFC). The vaccine was prepared by transfecting MFC total
      RNAs carrying the 4-1BBL gene into the DCs that were isolated from 615 mouse
      bones. The T cell proliferation rate in the MFC/4-1BBL/DC group was higher than
      that in the DC group. The tumor cell kill rate in the MFC/4-1BBL/DC group was
      higher than that in the DC group. ELISA analysis showed that IL-12 and IFN-gamma
      in the MFC/4-1BBL/DC group were more highly expressed compared to the other
      group. Collectively, our data demonstrate that the DC vaccine transfected with
      gastric cancer cell total RNA carrying the 4-1BBL gene has a stronger ability to
      kill gastric cancer cells through promoting T cell proliferation and enhancing
      the ability of cytotoxic T lymphocytes (CTLs) to kill gastric carcinoma cells and
      to secrete IL-12 and IFN-gamma. Our results provide an effective therapeutic
      strategy for treating gastric cancer using a DC vaccine.

PMID- 22969890
TI  - miR-196a2 polymorphisms and susceptibility to cancer: A meta-analysis involving
      24,697 subjects.
AB  - An increasing number of studies have shown that the hsa-miR-196a2 rs11614913
      polymorphism occurs in different types of cancer, but the results are generally
      controversial and inadequate, mainly due to limited statistical power. To resolve
      this issue, the present meta-analysis was carried out. Databases, including
      PubMed and Embase, were searched using: (miR-196a2[All Fields] OR rs11614913[All
      Fields]) AND ('neoplasms'[MeSH Terms] OR 'neoplasms'[All Fields] OR 'cancer'[All
      Fields]). Crude odds ratios (ORs) with 95% confidence intervals (CIs) were
      summarized in forest plots and detailed in tables. A total of 20 studies,
      including 11,004 cases and 13,693 controls, were included in the meta-analysis.
      The hsa-miR-196a2 rs11614913 polymorphism was significantly associated with an
      increased cancer risk in all genetic models (CC vs. TT: OR=1.280, 95% CI 1.131
      1.449, P<0.001; CT vs. TT: OR=1.187, 95% CI 1.079-1.306, P<0.001; CC/CT vs. TT:
      OR=1.216, 95% CI 1.104-1.341, P<0.001; and CC vs. CT/TT: OR=1.115, 95% CI 1.025
      1.213, P=0.011). In conclusion, this meta-analysis provides compelling evidence
      that the hsa-miR-196a2 rs11614913 polymorphism plays a crucial role in the
      development of cancer. Screening of patients for the hsa-miR-196a2 rs11614913
      polymorphism can prove clinically useful for the prediction and prevention of
      cancer.

PMID- 22969891
TI  - Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts
      poor outcome for patients with locally advanced breast cancer.
AB  - Patients with locally advanced breast cancer (LABC) commonly have an unfavorable
      prognosis. A molecular predictor for the identification of at-risk patients is
      urgently required. Thymidine kinase 1 in serum (S-TK1) is an enzyme involved in
      the synthesis of DNA precursors. In studies using immunohistochemistry, it was
      reported to be a more useful proliferation marker than Ki-67 in breast, lung and
      colorectal carcinoma. In the present study, we extended the research of prior
      breast carcinoma studies by postulating that in patients with LABC,
      overexpression of S-TK1 following neoadjuvant chemotherapy predicts cancer
      outcome. An experimental design consisting of 48 patients with LABC was
      prospectively constructed and analyzed. All patients received neoadjuvant
      chemotherapy and definitive surgical therapy. Study homogeneity was maintained by
      standardized treatment, surveillance and compliance protocols. The S-TK1
      concentration was detected using the anti-TK1 chicken IgY antibody, using a dot
      blot immuno-assay. After a median follow-up of 30 months, the results indicated a
      statistically significant trend (unadjusted). Patients with high S-TK1
      overexpression had a significantly higher incidence of recurrence (P=0.006) and
      cancer death (P= 0.0128) than those with low S-TK1 overexpression. A multivariate
      analysis provided identical results. The hazards ratio for developing recurrence
      in patients with higher S-TK1 expression was 6-7 times higher than the hazards
      ratio in patients with lower expression. In conclusion, our results indicate that
      a high S-TK1 concentration in sera from LABC patients receiving neoadjuvant
      chemotherapy is predictive of cancer outcome.

PMID- 22969892
TI  - Bladder cancer-associated protein is suppressed in human cervical tumors.
AB  - Bladder cancer-associated protein (BLCAP) is downregulated in bladder cancer and
      has been identified as a prognostic biomarker for human bladder cancer. We
      previously reported that BLCAP mRNA is decreased in cervical cancer tissues, and
      overexpression of BLCAP was found to inhibit cell growth and induce apoptosis in
      the human cervical cancer HeLa cell line To investigate the BLCAP protein
      expression in cervical cancer and its potential clinical indications, we
      developed a polyclonal antibody against human BLCAP to assess the BLCAP protein
      expression in 30 cervical cancer tissues and 30 non-tumor cervical tissues from
      patients. Western blotting data showed that a single band of recombinant protein
      was probed by antiserum of BLCAP and no band was probed by pre-immune serum.
      BLCAP expression was significantly downregulated in cervical carcinoma tissues
      compared with its expression in the non-tumor cervical tissues. Moreover,
      cervical carcinoma tissues from patients with stage III-IV had significantly
      lower BLCAP expression percentage compared with stage I-II. Similarly, a
      significantly lower BLCAP expression percentage was observed in moderately/poorly
      differentiated tumor tissues and in the tumor tissues from patients with
      lymphatic metastasis (LM) compared with well-differentiated tumor tissues and non
      LM patients, respectively. Our results suggest that decreased BLCAP protein
      expression is associated with poor prognosis and it could be a potential bio
      index to predict cervical tumor patient outcome.

PMID- 22969893
TI  - Expression of mitotic-arrest deficiency 2 predicts the efficacy of neoadjuvant
      chemotherapy for locally advanced uterine cervical cancer.
AB  - We previously reported satisfactory therapeutic results when using cisplatin
      based cyclic balloon-occluded arterial infusion chemotherapy as neoadjuvant
      chemotherapy (NAC), which enabled hysterectomy to be performed for patients with
      locally advanced cervical cancer. Mitotic arrest deficiency 2 (MAD2) is a key
      component of the mitotic spindle checkpoint pathway. The expression of MAD2 is
      associated with tumor progression and resistance to chemotherapy. Therefore, the
      aim of the present study was to examine whether the expression of MAD2 is related
      to the efficacy of NAC for locally advanced uterine cervical cancer. We reviewed
      53 cases of locally advanced uterine cervical cancer (stage IIIa-IIIb; based on
      the International Federation of Gynecology and Obstetrics criteria). These
      patients were initially treated at Osaka City University Medical School Hospital,
      Japan, from 1995 to 2008 and were under 70 years old. Tumor samples were obtained
      by biopsy prior to NAC. Cases were divided into two groups: one group in which
      NAC was effective, surgery was possible and radiotherapy was performed (NAC+OP+R
      group; n=33), and another group in which NAC was ineffective and radiation
      therapy was performed (NAC+R group; n=20). MAD2 expression was examined in
      paraffin-embedded sections using the avidin-biotin peroxidase complex method. The
      results showed that MAD2 expression was significantly higher in the NAC+R group
      compared to the NAC+OP+R group (P<0.001). There was no significant difference in
      overall survival between the two groups, although the prognosis for the NAC+OP+R
      group tended to be slightly better (P=0.064). Taken together, these results
      suggest that the expression of MAD2 may predict the efficacy of NAC as a
      treatment for locally advanced uterine cervical cancer.

PMID- 22969894
TI  - Administration of anti-vascular endothelial growth factor antibody following
      hepatectomy does not inhibit remnant liver regeneration or growth of remnant
      metastases.
AB  - In addition to the use of chemotherapeutic agents for the prevention of multiple
      liver metastases from colorectal cancer, the anti-vascular endothelial growth
      factor (VEGF) antibody, bevacizumab, is often used, and its effectiveness has
      been established. By contrast, it has been reported that the use of bevacizumab
      prior to or following surgery delays wound healing or liver regeneration. In this
      study, we investigated whether the administration of bevacizumab following
      hepatectomy inhibits remnant liver regeneration or the growth of remnant
      metastases. Mice were partially hepatectomized (31% of the liver was removed),
      transplanted with the murine colorectal cancer cell line, CT26, in the remnant
      lobe, and intraperitoneally injected with bevacizumab (4 mg/kg) for a total of 6
      times. Serum VEGF levels were measured on day 1 following surgery, and each lobe
      of the liver was weighed on day 14. Serum VEGF levels in non-hepatectomized,
      tumor-bearing mice exceeded those in their non-tumor-bearing counterparts;
      however, the administration of bevacizumab did not reduce the serum VEGF levels.
      The volume of the liver lobe of the hepatectomized, CT26-transplanted and non
      CT26-transplanted mice was 1,349.6 and 735.5 mg, respectively, indicating rapid
      growth of the CT26 transplant (p=0.023). The volume of the CT26-transplanted lobe
      of the bevacizumab-administered mice was 1,379.0 mg, which was not significantly
      different from that (1,349.6 mg) of the non-bevacizumab-administered mice. The
      volume of the remnant lobe of the bevacizumab-administered mice was 1,051.0 mg,
      which did not significantly differ from that (957.3 mg) of the non-bevacizumab
      administered mice. The administration of bevacizumab following hepatectomy did
      not delay remnant liver regeneration, and did not suppress the growth of
      metastases in the remnant lobes or remnant liver regeneration.

PMID- 22969895
TI  - miRNA expression profile in primary gastric cancers and paired lymph node
      metastases indicates that miR-10a plays a role in metastasis from primary gastric
      cancer to lymph nodes.
AB  - The aim of this study was to identify and evaluate microRNAs (miRNAs) in gastric
      cancer lymph node metastasis. A miRNA array was used to compare the expression of
      miRNAs in primary gastric cancer and paired lymph node metastases. miRNAs found
      to be differentially expressed were validated in a cohort of primary gastric
      cancer tissues, and the relationship between expression and the
      clinicopathological characteristics of the specimens was analyzed. The expression
      level of miR-10a in a gastric mucosal cell line and three gastric cancer cell
      lines was also detected using qPCR. Moreover, the target genes for miR-10a were
      predicted using bioinformatic methods. Based on the results, four differentially
      expressed miRNAs were detected by the miRNA array. Compared with primary gastric
      cancer, lymph node metastases displayed downregulated expression of miR-24-1(*),
      miR-510 and miR-1284, while the expression of miR-10a was upregulated.
      Consequently, analysis found that the expression of miR-10a was associated with
      lymph node metastasis (P=0.047), but was independent of the state of lymphatic
      invasion (P=0.169) in the cohort of primary gastric carcinoma. The expression of
      miR-10a was at least 10-fold higher in the three gastric cancer cell lines than
      in the gastric mucosal cell line. Two gastric cancer cell lines, which were
      established from lymph node metastasis, expressed higher miR-10a compared to the
      primary tumor origin cell line. Bioinformatic analysis demonstrated that the
      target genes of miR-10a are involved in multiple related pathways of
      tumorigenesis and metastasis. In conclusion, our study suggests that miR-10a is
      involved in the development of gastric cancer and lymph node metastasis,
      particularly in the latter process.

PMID- 22969896
TI  - gamma-secretase inhibition combined with cisplatin enhances apoptosis of
      nasopharyngeal carcinoma cells.
AB  - The Notch signaling pathway plays an important role in the proliferation and
      differentiation of cells. Although recent studies have shown that Notch plays a
      role in the mechanisms of cisplatin resistance, the mechanism by which Notch
      plays roles in intrinsic or acquired cisplatin resistance remains unclear. In the
      present study, poorly differentiated nasopharyngeal carcinoma cells were treated
      with a gamma-secretase inhibitor (DAPT), which led to a decrease in the Notch
      intracellular domain and inhibition of Notch signaling. Treatment was not
      sufficient to induce pronounced apoptosis of CNE-2 cells, but did result in the
      down-regulation of the P-glycoprotein and ERCC1 protein. In contrast, the
      combined treatment of DAPT and cisplatin induced substantial cell apoptosis
      compared to cisplatin treatment alone.

PMID- 22969897
TI  - Interaction of Staphylococcus aureus with osteoblasts (Review).
AB  - Orthopedic infection is refractory to cure. Staphylococcus aureus (S. aureus) is
      the main causative pathogen responsible for orthopedic infection. S. aureus is
      capable of not only colonizing bone matrix, but also invading osteoblasts, which
      may play a significant role in the persistence and recurrence of osteomyelitis.
      Internalization requires the involvement of cytoskeletal elements, including
      actin microfilaments, microtubules and clathrin-coated pits. Microfilaments are
      most significant in the invasion process. S. aureus is capable of remaining alive
      in osteoblasts for a long period of time. Decreased sensitivity to antibiotics
      capable of penetrating host cells increases the difficulties of eradicating S.
      aureus. Osteoblasts, invaded by S. aureus, play a significant role in the
      initiation and maintenance of inflammatory immune responses. These osteoblasts
      recruit leukocytes and phagocytes to the site of inflammation via the expression
      of cytokines. Apoptosis is observed in osteoblasts invaded by S. aureus.
      Recruitment of osteoclasts and other immunocytes plays a crucial role in the
      resorption and destruction of bone.

PMID- 22969898
TI  - Sequential analysis of diethylnitrosamine-induced hepatocarcinogenesis in rats.
AB  - In the present study, we examined the sequential changes of diethylnitrosamine
      (DEN)-induced hepatocarcinogenesis in Wistar rats. After 14 weeks of DEN
      treatment, hyperplastic nodules developed as a consequence of the appearance of
      renewed hepatocytes, degenerated hepatocytes, oval cells and fibrotic changes.
      Total bilirubin and alanine aminotransferase levels were significantly higher in
      the DEN group compared to the control group throughout the experimental period.
      Our data may prove beneficial to future analyses of chemopreventive compounds
      during various stages of hepatocarcinogenesis in rats.

PMID- 22969899
TI  - Upregulation of nuclear PA28gamma expression in cirrhosis and hepatocellular
      carcinoma.
AB  - We previously reported that proteasome activator 28gamma (PA28gamma) is an
      oncogenic protein in hepatitis C virus (HCV) core protein transgenic mice. The
      aim of this study was to determine the role of PA28gamma expression at the
      protein level in the development and progression of human hepatocarcinogenesis
      and hepatocellular carcinoma (HCC). Samples from tissues representing a wide
      spectrum of liver disease were analyzed, including histologically normal livers
      (n=5), HCV-related chronic hepatitis (CH) (n=15) and cirrhosis (n=31). The level
      of nuclear PA28gamma increased with the progression of liver disease from CH to
      cirrhosis. The majority of cirrhotic livers (68%; 21/31) displayed high nuclear
      PA28gamma expression. However, in half of the HCCs (50%; 18/36), little or no
      nuclear PA28gamma expression was observed, while the remaining 50% (18/36) of the
      cases displayed high levels of nuclear PA28gamma expression. A
      clinicopathological survey demonstrated a significant correlation between nuclear
      PA28gamma expression and capsular invasion in HCC (P=0.026); a striking
      difference was found between nuclear PA28gamma expression in non-tumor tissues
      and shorter disease-free survival (P<0.01). Moreover, nuclear PA28gamma
      expression in non-tumor tissues correlated with the expression of molecules
      related to the genesis of hepatic steatosis and HCC, such as sterol regulatory
      element binding protein-1c mRNA. The findings suggest the involvement of nuclear
      PA28gamma expression in the progression and relapse of HCC, and suggest that
      nuclear PA28gamma is a potentially suitable target for the prevention and/or
      treatment of HCC.

PMID- 22969900
TI  - Considerations for two inoculation methods of rabbit hepatic tumors: Pathology
      and image features.
AB  - The rabbit VX2 hepatic tumor model has been widely used for the investigation of
      liver cancer. The present study was designed to compare two inoculation methods
      in order to identify an improved modality for establishing rabbit hepatic tumors.
      A total of 44 rabbits were randomly divided into 2 groups. All inoculations were
      performed by open laparotomy. In group 1, 22 rabbits received a VX2 tumor cell
      suspension in a volume of 0.2 ml, which was slowly injected into the rabbit liver
      parenchyma using an 18-gauge needle. In group 2, a 0.2-ml suspension of small,
      minced tumor fragments of a VX2 carcinoma, inserted into an 18-gauge needle, was
      implanted into the liver parenchyma. The tumor survival ratio, size and
      extrahepatic metastases were evaluated and compared using computed tomography
      (CT)-scan, angiography and pathological specimens. At 2 weeks following
      implantation, successful liver tumor growth was achieved in 14 out of the 22
      rabbits in group 1 (63.6%) and 21 out of the 22 rabbits in group 2 (95.5%)
      (P<0.05). Further sub-analysis revealed that single nodular tumors in the liver
      were observed in 4 out of the 14 rabbits in group 1 (28.6%) and 14 out of the 21
      rabbits in group 2 (66.7%), and that multinodular tumors in the liver were
      observed in 10 out of the 14 rabbits in group 1 (71.4%) and 7 out of the 21
      rabbits in group 2 (33.3%) (P<0.05). Extrahepatic metastases were observed in 5
      out of the 14 rabbits in group 1 (35.7%) and 1 of the 21 rabbits in group 2
      (4.8%) (P<0.05). Imaging findings of hepatic tumors were in concordance with
      histopathology. In conclusion, direct implantation of VX2 tumor fragments into
      the liver using a fine needle achieved a higher success rate than injecting VX2
      tumor cells. The rabbit hepatic tumors inoculated by this method may therefore be
      a more suitable animal model for investigating liver cancer.

PMID- 22969901
TI  - Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma
      patients.
AB  - RASSF2 has recently been identified as a potential tumor suppressor that serves
      as a Ras effector in various types of human cancers. However, there have been few
      reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from
      276 Chinese patients with follow-up were analyzed for RASSF2 protein expression
      by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this
      group of gastric carcinoma. The expression of RASSF2 was significantly lower in
      carcinomas than in normal mucosas (P<0.05). RASSF2 corresponded positively with
      patient age, histological differentiation, depth of tumor invasion, regional
      lymph node and distant metastasis, and TNM stage (all P<0.05). Further
      multivariate analysis revealed that patient gender, depth of tumor invasion,
      distant metastasis, TNM stage and the expression of RASSF2 were independent
      prognostic factors for patients with gastric cancer. The Kaplan-Meier plot showed
      that the overall mean survival time of the patients with RASSF2-negative
      expression was shorter than that of patients with positive expression
      (chi(2)=156.874, P<0.0001). Moreover, RASSF2-negative expression had a much more
      significant effect on the survival of those patients with early stage tumors
      (chi(2)=127.167, P<0.0001), highlighted by a >50.9% reduction in 3-year survival
      compared to that of patients with RASSF2-positive expression. In late stages, the
      difference was also significant (chi(2)=6.246, P=0.019), with a 35.5% reduction
      in 3-year survival. It is suggested that RASSF2 plays an important role in the
      evolution of gastric adenocarcinoma and should be considered as a potential
      marker for its prognosis.

PMID- 22969902
TI  - Analysis of immunoexpression of common cancer stem cell markers in ameloblastoma.
AB  - Recent studies have established that, in benign tumors, a large number of cancer
      stem cells are present, which have great implications in tumor development.
      However, in ameloblastoma, a highly aggressive, locally invasive tumor with a
      high recurrence rate, whether or not cancer stem-like cells are present remains
      undetermined. Therefore, in this study we analyzed the protein expression of
      three candidate stem cell markers in ameloblastoma. Immunohistochemical staining
      for cancer stem cell (CSC) markers (CD133, CD44 and ABCG2) and for the
      proliferation marker Ki-67 was performed using 23 ameloblastoma cases. In all 23
      samples, CD133, CD44 and ABCG2 were expressed. Nine (39.13%) cases showed high
      expression and 14 cases (60.87%) showed low expression for CD133. Twelve of the
      23 cases (52.17%) showed high expression and 11 cases (47.83%) showed low
      expression for both CD44 and ABCG2, respectively. Ki-67 was mainly expressed in
      peripheral ameloblast-like cells, suggesting that these cells have a higher
      degree of differentiation and, therefore, are less likely to contain cancer stem
      like cells. On the other hand, cells positive for CSC markers situated at the
      close proximity to peripheral cells were devoid of Ki-67 and may have the
      potential to be cancer stem-like cells. After analyzing the correlation between
      expression of three CSC markers with clinicopathological factors and Ki-67
      expression, only CD44 expression was correlated with tumor recurrence (P=0.0391).
      In conclusion, this study showed various expression patterns of different types
      of cancer stem cell markers and the presence of candidate CSC-like cells in
      ameloblastoma, which are possibly involved in cell proliferation, tumor
      progression and recurrence.

PMID- 22969903
TI  - Clinical significance of radiation-induced CD133 expression in residual rectal
      cancer cells after chemoradiotherapy.
AB  - CD133 and CD44 have been considered as markers for colorectal cancer stem cells
      (CSCs). The association of CD133 and CD44 expression with radiation has not been
      fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were
      measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients
      using real-time RT-PCR and compared to clinicopathological variables and clinical
      outcome. Their protein levels were examined in the radiation-treated HT29 human
      colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly
      higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44
      was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with
      distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated
      CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No
      significant association between post-CRT CD44 and clinical outcome was found. The
      in vitro study showed that CD133 protein was increased in a radiation dose
      dependent manner, despite of the decreased number of clonogenic radiation
      surviving cells. CD44 protein was decreased after irradiation. CD133, but not
      CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT
      CD133 in residual cancer cells may predict metachronous distant recurrence and
      poor survival of rectal cancer patients after CRT.

PMID- 22969904
TI  - Use of a murine endometriosis interna model for the characterization of compounds
      that effectively treat human endometriosis.
AB  - Endometriosis is a chronic, estrogen-dependent disease characterized by the
      presence of ectopic endometrium either in the pelvic cavity (endometriosis
      externa) or within the uterus (endometriosis interna, adenomyosis). Key symptoms
      are pelvic pain, dysmenorrhea and infertility. Established rodent animal models
      used for drug research in endometriosis have certain limitations. Since rodents
      do not menstruate, they cannot develop endometriosis externa spontaneously, but
      they suffer from endometriosis interna. There is growing evidence that human
      endometriosis externa and interna represent two faces of the same disease. Both
      are estrogen-dependent and respond to similar treatment paradigms. Here, we
      addressed the question whether a murine endometriosis interna model may also be
      suitable for the characterization of drugs employed in human endometriosis. We
      examined the effects of danazol, Faslodex and cetrorelix in SHN mice that
      developed endometriosis interna after pituitary grafting. The GnRH antagonist
      cetrorelix and the estrogen receptor antagonist Faslodex, which negatively
      interfered with estrogen-mediated signaling, completely inhibited endometriosis
      interna, whereas danazol, an androgenic progestin, showed significant therapeutic
      activity in the majority of SHN mice. We conclude that this murine endometriosis
      interna model may be a valuable complement to established endometriosis externa
      models to support drug research in human endometriosis.

PMID- 22969905
TI  - Glycan-related gene expression signatures in human metastatic hepatocellular
      carcinoma cells.
AB  - Human hepatocellular carcinoma (HCC) ranks second in cancer mortality in China;
      recurrence and metastasis have been the cause of the high mortality. Glycans on
      the cell surface play a pivotal role in tumor metastasis. The global alteration
      in the structure and composition of N-glycans during HCC metastasis remains
      unknown. To understand glycan alterations of glycoproteins by correlating the
      glycosyltransferase expression profile with glycan structure, we systematically
      used glycan profiling tools: glycogene microarray analyses of 115 genes,
      including glycotransferases, glycosidases and nuclear sugar transporters and
      lectin chips to investigate the glycan-related gene expression signatures in the
      high metastatic potential HCC cell line, HCCLM3, in comparison to the HCC cell
      line, Hep3B, with low metastatic potential. Of the 115 genes, 18 genes were up
      regulated in high metastatic potential HCCLM3 cells in comparison to Hep3B cells,
      while 11 genes were down-regulated. The differentially expressed genes, such as
      ST3GalI, FUT8, beta3GalT5, MGAT3 and MGAT5, were mainly involved in the synthesis
      of N-glycan and glycolipids, particularly the sialyl Lewis antigen. The results
      of the glycogene microarray analysis were further validated by quantitative real
      time PCR analysis and lectin-based analysis. The differentially expressed
      glycogenes identified in this study may provide new insights and represent novel
      factors for investigating the functional role of cell surface carbohydrate
      mediated HCC metastasis.

PMID- 22969906
TI  - Prognostic factors in patients with pancreatic cancer.
AB  - The identification of prognostic factors for pancreatic cancer patients could
      provide insightful information for their management in the clinic. A total of 302
      pancreatic cancer patients were enrolled in this study. The clinicopathological
      characteristics, treatment selection and laboratory test data were
      retrospectively retrieved from the medical records and follow-up data were
      obtained via telephone interview. Cox survival analysis was used to assess the
      potential prognostic factors, and survival curves were obtained by Kaplan-Meier
      analyses. The mortality rate of the patients was 83.4% (252/302) and the median
      survival of these patients was 6.1 months, with 1-, 2- and 3-year survival rates
      of 30.1 (91/302), 10.6 (32/302) and 2.6% (8/302), respectively. The most
      influential factors for the survival of these patients were the site of primary
      cancer, tumor stage, treatment selection, serum levels of glutamic-pyruvic
      transaminase, albumin, lactate dehydrogenase and hemoglobin, and white blood cell
      counts (P<0.05). The median survival of patients who did not receive any
      treatment or just received supportive treatment was 1.3 months, while the median
      overall survival of patients who underwent surgery, chemotherapy, biliary
      drainage therapy, arterial interventional chemotherapy and comprehensive
      treatment was 11.0, 7.3, 3.5, 9.0 and 11.0 months, respectively (P<0.05).
      Furthermore, single-drug chemotherapy was not statistically associated with
      patient survival in those who received the multi-drug regimen (P>0.05). However,
      the mortality risk of patients who received platinum chemotherapy was decreased
      [hazard ratio (HR)=0.56, 95% CI 0.35-0.88, P=0.011] compared to the patients who
      did not receive this treatment (P<0.05). Tumor stage, treatment selection, serum
      albumin levels, urea nitrogen, CA19-9, white blood cell and platelet counts were
      independent prognostic factors for the prediction of survival in pancreatic
      cancer. Future studies are required in order to verify these data. Chemotherapy
      with platinum regimens could improve overall survival in patients with pancreatic
      cancer.

PMID- 22969907
TI  - Investigation of thrombospondin-1 and transforming growth factor-beta expression
      in the heart of aging mice.
AB  - Elderly patients face the problems of morbidity and mortality due to age-mediated
      disabilities. The purpose of the present study was to investigate the expression
      of thrombospondin-1 (TSP-1) and transforming growth factor-beta (TGF-beta) in
      aging mice, and its probable mechanism in the pathological changes of aging
      myocardium. The aging model group (AM) comprised 30-month-old mice, while the
      control group comprised 2-month-old mice. The pathological changes were explored
      by H&E staining, and the contents of superoxide dismulase (SOD) and
      malondialdehyde (MDA) in the hearts were determined by xanthine oxidation or TBA
      colorimetry. TSP-1 and TGF-beta expression in the left ventricular myocardium was
      also measured by immunohistochemistry. The results showed that the activities of
      SOD decreased and the MDA content increased markedly in the hearts of the AM
      group compared to the control group. H&E staining showed that the control group
      myocardial cells lined up in order with clear structure and stained equably,
      while the AM group myocardial cells lined up in disorder with an augmented cell
      body and the appearance of many granules and interstitial fibrosis. Compared to
      the control group, in the hearts of the AM group, TSP-1 and TGF-beta protein
      expression in myocardial cells showed a significant increase (P<0.01). TSP-1 and
      TGF-beta expression increased in the myocardium, which may be related to
      pathological changes of age-related heart diseases, such as hypertrophy, fibrosis
      of myocardial cells and microvessel dissepiment thickening.

PMID- 22969908
TI  - Upregulation of TCTP expression in human skin squamous cell carcinoma increases
      tumor cell viability through anti-apoptotic action of the protein.
AB  - The translationally controlled tumor protein (TCTP) is an anti-apoptotic protein,
      which is highly expressed in several human cancer types. However, the role of
      TCTP in skin cancers, including squamous cell carcinoma (SCC), has not been
      investigated. In this study, we analyzed the expression of TCTP in cutaneous SCC
      samples using immunohistochemistry in two epidermoid SCC cell lines, A431 and SCL
      1, using western blot analysis. We further investigated the role of TCTP in skin
      cancinogenesis by silencing the TPT1 gene using small interfering RNA (siRNA) in
      the SCC cell line A431. Our results demonstrated that TCTP was overexpressed in
      cutaneous SCC cells, compared to normal skin keratinocytes. In addition, the
      expression of TCTP in skin SCC significantly increased with the grade of
      malignancy. Western blot analysis further confirmed that the expression of TCTP
      in the cell lines, A431 and SCL-1, was significantly higher compared to that in
      the normal keratinocyte cell line, HaCaT. The expression of TCTP in A431 cells
      was significantly downregulated by transfection with our specifically designed
      TCTP siRNA. We found that downregulation of TCTP expression was associated with
      decreased cell proliferation and increased apoptosis in A431 cells. These results
      suggest that the TPT1 gene may be a potential therapeutic target in skin SCC
      through a siRNA approach.

PMID- 22969909
TI  - Downregulation of keratins 8, 18 and 19 influences invasiveness of human cultured
      squamous cell carcinoma and adenocarcinoma cells.
AB  - Keratin (K) expression index has been reported to be related to cell invasion
      activity in adenocarcinoma. In a previous study, we observed a negative
      correlation between K expression and cell invasion activity; i.e., when many Ks
      are expressed in the cells, the cell activity is low. To further elucidate the
      correlation between Ks and invasion activity, RNA interference experiments of K8,
      K18 and K19 were carried out to clarify the essential role of Ks using T24 and
      HEC-1 as typical squamous cell carcinoma and adenocarcinoma cells, respectively.
      K8 small interfering RNA (siRNA) was most effective against K18 and K19
      expression and demonstrated the strongest effect on relative invasion activity
      among the siRNAs used. These results suggest that K8/K18 or K8/K19 filaments may
      play roles in internal cell structure and invasion activity. Moreover, K18 and
      K19 were capable of substituting for each other, and K18 or K19 formed filaments
      with K8. In addition, cells treated with K8 siRNA demonstrated high invasion
      activity, which was approximately double that observed with control siRNA in HEC
      1 cells. The order of effects was K8>K19>K18 in the two cell lines. The above
      results suggest that K8 may play a signifiant role in invasive functions in
      epithelial and metastatic cells.

PMID- 22969910
TI  - Synchronous and metachronous lung metastases in patients with colorectal cancer:
      A 20-year monocentric experience.
AB  - There is little information regarding the recent trend of synchronous and
      metachronous pulmonary metastases in patients with primary colorectal cancer. We
      investigated patients with sporadic colorectal cancer who underwent surgery in
      our department between 1990 and 2009. Clinicopathological parameters of primary
      cancer and lung metastases and survival time were retrospectively reviewed. Of
      the 2,286 patients included in this study, 64 (2.8%) had synchronous lung
      metastases at the time of colorectal surgery. A total of 18 patients (28%)
      received pulmonary metastasectomy for these lesions with curative intent. Out of
      2,082 curatively operated cases, 212 (10.2%) developed metachronous lung
      metastases. The frequency of synchronous and/or metachronous lung metastases
      detected in curative cases increased from 8.9% in the 1990s to 11.9% in the 2000s
      (p=0.03). Among predictive factors for metachronous lung metastases, the presence
      of distant organ metastases, i.e. initial stage IV, significantly increased over
      time. Notably, patients with unresectable metachronous lung metastases in the
      2000s, characterized by smaller size, exhibited more favorable prognosis than in
      the 1990s (p=0.003). Recent improvement of imaging modalities is considered to
      have facilitated the prompt diagnosis of lung metastases. Moreover, marked
      progress in multidisciplinary treatment has presumably achieved more favorable
      prognosis in an increasing number of patients with advanced colorectal cancer.

PMID- 22969911
TI  - Effect of a chicken comb extract-containing supplement on subclinical joint pain
      in collegiate soccer players.
AB  - Much of our focus of attention has been on sub-clinical or subtle joint pain
      experienced by healthy soccer players. The present study aimed to determine at
      which joint such subclinical pains are the most prominent, and to examine the
      pain-relieving effect of a chicken comb extract (CCE)-containing supplement
      product (test product) on these athletes. A total of 46 collegiate soccer
      players, consisting of 24 leading and 22 substitute players, belonging to a
      university soccer team were enrolled for measuring the pains at 4 different
      joints (ankle, knee, hip and shoulder) using 3 pain subscales of a 100-mm visual
      analog scale (VAS) ('pain at rest', 'pain on pressing' and 'pain on moving'), and
      participated in a prospective, double-blind, controlled study. A total of 23
      subjects each received the test product (4,800 mg/day) (test group) and placebo
      (placebo group) for 12 weeks. VAS pain scores of individual joints were evaluated
      at baseline and following 4, 8 and 12 weeks of the intervention. VAS scores for
      the 'pain on moving' subscale in 46 enrolled subjects were highest at the ankle
      joint, and thus the values (abbreviated as 'pain scores') were used as a
      parameter for efficacy assessment of the test product. Compared to the baseline,
      the pain scores were significantly decreased for the dominant foot (but not for
      the non-dominant foot) in the total subpopulation (at week 4; p<0.01) and the
      leading player subpopulation (at week 4; p<0.01 and at week 12; p<0.05) in the
      test group (n=19 and 11, respectively). In comparison between the test product
      and placebo groups, the pain scores were significantly changed for the dominant
      foot (p<0.05) at week 4 in the total subpopulation and at week 12 in the leading
      player subpopulation in the test group. Thus, subclinical joint pain is most
      prominently observed at the ankle joint of the dominant foot in healthy young
      soccer players and may be improved by the daily intake of the CCE-containing
      supplement.

PMID- 22969912
TI  - Personalized peptide vaccination for advanced biliary tract cancer: IL-6,
      nutritional status and pre-existing antigen-specific immunity as possible
      biomarkers for patient prognosis.
AB  - Considering that the prognosis of patients with advanced biliary tract cancer
      (BTC) remains very poor, with a median survival of less than 1 year, new
      therapeutic approaches need to be developed. In the present study, a phase II
      clinical trial of personalized peptide vaccination (PPV) was conducted in
      advanced BTC patients to evaluate the feasibility of this treatment and to
      identify potential biomarkers. A maximum of 4 human leukocyte antigen-matched
      peptides, which were selected based on the pre-existing host immunity prior to
      vaccination, were subcutaneously administered (weekly for 6 consecutive weeks and
      bi-weekly thereafter) to 25 advanced BTC patients without severe adverse events.
      Humoral and/or T cell responses specific to the vaccine antigens were
      substantially induced in a subset of the vaccinated patients. As shown by
      multivariate Cox regression analysis, lower interleukin-6 (IL-6) and higher
      albumin levels prior to vaccination and greater numbers of selected vaccine
      peptides were significantly favorable factors for overall survival [hazard ratio
      (HR)=1.123, 95% confidence interval (CI) 1.008-1.252, P=0.035; HR=0.158, 95% CI
      0.029-0.860, P=0.033; HR=0.258, 95% CI 0.098-0.682, P=0.006; respectively]. Based
      on the safety profile and substantial immune responses to vaccine antigens, PPV
      could be a promising approach for refractory BTC, although its clinical efficacy
      remains to be investigated in larger-scale prospective studies. The identified
      biomarkers are potentially useful for selecting BTC patients who would benefit
      from PPV.

PMID- 22969913
TI  - Comparative proteomic analysis of the function and network mechanisms of MASPIN
      in human lung cells.
AB  - MASPIN, which is also known as Serpin B5, is a novel tumor suppressor. Emerging
      evidence suggests that MASPIN acts as a multifaceted protein in various types of
      cancer, including prostate, breast and pancreatic cancer. It interacts with
      diverse groups of intercellular and extracellular proteins, regulating cell
      adhesion, motility, apoptosis and angiogenesis, and is involved in mammary gland
      development. As MASPIN is a multifunctional factor in cancer pathways, its
      function remains poorly illuminated. In this study, we compared the protein
      profiles of LC5 cell lines with MASPIN overexpression and knockdown using
      comparative two-dimensional gel electrophoresis. The differences in protein
      expression, visualized as differences in spots, were identified by time-of-flight
      (TOF)/TOF mass spectometry. Significant differences were observed between
      overexpressing and knocked down cells, including eight spots that were unique and
      sixteen spots that were up- or down-regulated by more than 4-fold. Six genes,
      including Sdccag8, Ldoc1, SCAI, SDCCAG3, CT62 and NEDD9 were unique in MASPIN
      expressing cell lines, but absent in knock-out cell lines, in which most of them
      play a significant role in the invasion of cancer cells. Moreover, the Brms1 and
      CAGE1 genes were identified as being uniquely expressed in knocked down cell
      lines, which were associated with the development and progression of tumors. The
      data from this study shed some light on the function, as well as the general
      network mechanisms of MASPIN in lung cancer.

PMID- 22969914
TI  - miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w.
AB  - microRNAs are a small class of non-coding RNAs with a critical role in the
      tumorigenesis and maintenance of breast cancer through binding to the 3'
      untranslated regions of target mRNAs, which causes a block of translation and/or
      mRNA degradation. The purpose of this study was to investigate the expression of
      microRNA-497 (miR-497) as well as its potential role in human breast cancer.
      Reverse transcription-polymerase chain reaction (RT-PCR) was performed to
      determine the expression pattern of miR-497 in breast cancer and normal breast
      tissues. Correlation analysis was conducted to characterize the association of
      miR-497 expression abnormality with pathological factors. Proliferation, cell
      cycle and apoptosis assays were conducted to explore the potential function of
      miR-497 in human MCF-7 breast cancer cells. RT-PCR and Western blot analysis were
      employed to validate the downstream targets of miR-497. miR-497 expression was
      relatively decreased in breast cancer specimens and negatively correlated with
      TNM stage, lymphatic metastasis, tumor size and human epidermal growth factor
      receptor-2 (P<0.01). On the contrary, no correlation was found with estrogen
      receptor, progesterone receptor and p53 status. Functional assays revealed that
      miR-497 suppressed cellular growth, increased the percentage of early apoptotic
      cells and initiated G0/G1 cell phase arrest of MCF-7 cancer cells. RT-PCR and
      Western blot analysis data indicated that the overexpression of miR-497 resulted
      in the down-regulation of Bcl-w at the mRNA and protein levels. miR-497 may serve
      as a tumor suppressor gene in breast cancer. The Up-regulation of miR-497
      expression causes cellular growth inhibition and apoptotic enhancement, as well
      as G0/ G1 phase arrest, suggesting its use as a potential therapeutic target for
      the treatment of breast cancer in the future.

PMID- 22969915
TI  - Therapeutic efficacy of Bifidobacterium longum-mediated human interleukin-2 with
      endostatin or TRAIL in transplanted tumors in mice.
AB  - Interleukin-2 (IL-2), as an important cytokine in immune response, has been
      demonstrated to have therapeutic activity in several cancer models. In our
      previous study, we showed that the pBV22210 vector containing a chloramphenicol
      resistance gene and the cryptic plasmid, pMB1, from the Bifidobacterium longum
      (B. longum) strain could stably replicate and did not significantly affect the
      biological characteristics of B. longum. In this study, B. longum was transfected
      by electroporation with pBV22210 containing IL-2 (B. longum-pBV22210-IL-2), its
      growth curve was determined, and its inhibitory effect on tumor xenografts in
      mice was examined. The results showed that B. longum-pBV22210-IL-2 reduced the
      tumor size and prolonged the survival time of H22 tumor-bearing mice. In
      addition, when cyclophosphamide (CTX), B. longum-pBV22210-endostatin, or B.
      longum-pBV22210-TRAIL was combined with B. longum-pBV22210-IL-2, the antitumor
      effect was significantly enhanced. The survival times of the mice in the
      combination groups of B. longum-pBV22210-endostatin or B. longum-pBV22210-TRAIL
      were longer than those of the mice in the B. longum-pBV22210-IL-2 alone group.
      However, when CTX was added, the survival times of the mice showed no
      statistically significant difference compared with those of the mice in the
      dextrose-saline solution group. These results suggest that B. longum-pBV22210-IL
      2 has potent antitumor effects that could be enhanced when combined with
      chemotherapeutic drugs or other antitumor genes.

PMID- 22969916
TI  - CHOP and caspase 3 induction underlie glioblastoma cell death in response to
      endoplasmic reticulum stress.
AB  - The unfolded protein endoplasmic reticulum stress response has emerged as a
      cellular physiological target to invoke tumor cell killing due to its homeostatic
      and cytoprotective functions. In this study, thapsigargin and tunicamycin, two
      endoplasmic reticulum stress inducers, were investigated for their efficacy on
      glioblastomas. We demonstrate that clinically relevant concentrations of
      thapsigargin and tunicamycin eliminate the glioblastoma cell reproductive
      capacity as a consequence of cell death. The mode of glioblastoma-induced cell
      death was determined to be via apoptosis as supported by increased C/EBP
      homologous protein (CHOP) levels and caspase 3 activity, two proteins with
      established roles in endoplasmic reticulum stress-induced cell death. In
      conclusion, this study provides evidence that glioblastomas are responsive to
      endoplasmic reticulum stress induction as a cellular program to eradicate this
      tumor via programmed cell death.

PMID- 22969917
TI  - No association of the MTHFR gene A1298C polymorphism with the risk of prostate
      cancer: A meta-analysis.
AB  - Various studies have demonstrated that the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene polymorphism contributes to the risk of prostate cancer,
      while other studies have provided conflicting findings. In the present study, we
      carried out a comprehensive meta-analysis with the aim of determining whether
      there is a significant association of the MTHFR gene A1298C polymorphism with the
      susceptibility of prostate cancer. Studies on the MTHFR gene A1298C polymorphism
      and prostate cancer were retrieved using the electronic PubMed database without
      any restriction on language through Aug 21, 2011. Data were abstracted by a
      standardized protocol. Crude odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated to estimate the strength of association. The analyses were
      conducted with Review Manager software version 4.2. Nine case-control studies
      were identified, including 2,723 prostate cancer patients and 3,442 controls.
      Overall, no significant associations were found between the MTHFR gene A1298C
      polymorphism and prostate cancer (codominant models: CC vs. AA, OR=1.03, 95% CI
      0.79-1.34, P=0.84; AC vs. AA, OR=1.04, 95% CI 0.93-1.16, P=0.46; dominant model:
      AC + CC vs. AA, OR=1.04, 95% CI 0.94-1.15, P=0.48; recessive model: CC vs. AC +
      AA, OR=1.02, 95% CI 0.76-1.35, P=0.91; allele model: C vs. A, OR=1.04, 95% CI
      0.90-1.19, P=0.61). Similarly, in the subgroup analyses by DNA source, ethnicity,
      control source, pathological stage and Hardy-Weinberg equilibrium, no significant
      associations were observed. Our meta-analysis suggests that the MTHFR gene A1298C
      polymorphism is not associated with the risk of prostate cancer.

PMID- 22969918
TI  - Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular
      carcinoma.
AB  - The accumulation of single nucleotide polymorphisms (SNPs) in the displacement
      loop (D-loop) of mitochondrial DNA (mtDNA) has been associated with various types
      of cancer. The association of SNPs with cancer risk and disease outcome has been
      exhaustively studied. In this study, we investigated the association of age-at
      onset and SNPs in the mitochondrial D-loop using a population-based series of
      hepatocellular carcinoma (HCC) patients. Haplogroup M (489C) and allele 235G were
      identified for their association with the late onset of HCC by the log-rank test.
      In an overall multivariate analysis, haplogroup M (489C) was identified as an
      independent predictive factor for the age-at-onset of HCC at borderline
      significant levels [relative risk, 1.736; 95% confidence interval (CI), 0.967
      3.115; p=0.065]. Genetic polymorphisms in the D-loop are predictive markers for
      age-at-onset in HCC patients. Accordingly, the analysis of genetic polymorphisms
      in the mitochondrial D-loop may help to identify HCC patient subgroups at high
      risk of early onset of the disease.

PMID- 22969919
TI  - LNA real-time PCR probe quantification of hepatitis B virus DNA.
AB  - In the present study, we standardized a TaqMan locked nucleic acid (LNA) real
      time polymerase chain reaction (PCR) probe for the accurate quantification and
      detection of hepatitis B virus (HBV) DNA in serum (plasma), and evaluated its
      methodology. LNA probe technology had a much better detection performance in HBV
      DNA than the common TaqMan probe. The assay based on the LNA probe had a wider
      linear detection range, higher sensitivity, stability and amplification
      efficiency, and a lower concentration of probes than the TaqMan probe. Among the
      15 cases with chronic hepatitis B surface antigen (HBsAg) (+) alone, only 4 cases
      that were detected by TaqMan real-time PCR were negative; however, the same
      samples were positive by LNA real-time PCR (p<0.05). A positive correlation
      between viral load measurements for the 35 samples with HBV-positive DNA was
      detected in both LNA and TaqMan real-time PCR.

PMID- 22969920
TI  - Association between the M235T polymorphism of the AGT gene and cytokines in
      patients with hypertension.
AB  - The aim of the present study was to explore the association between the M235T
      polymorphism of the angiotensinogen (AGT) gene and cytokines in patients with
      essential hypertension (EH). A total of 300 patients with EH and an age-matched
      control group of 150 individuals without EH, secondary hypertension, myocardial
      infarction and diabetes were enrolled in this study. Polymerase chain reaction
      combined with restriction fragment length polymorphism (PCR-RFLP) was used to
      detect variation in the target genotype, and enzyme-linked immunosorbant assay
      (ELISA) was used to detect the cytokine [interleukin (IL)-1, IL-6 and tumor
      necrosis factor-alpha (TNF-alpha)] concentrations. The AGT gene 235T allele and
      235TT genotype frequencies in hypertensive patients were slightly higher than
      those in the controls. Furthermore, in the hypertensive subjects with the AGT
      gene 235T allele, the concentrations of IL-1 and TNF-alpha were significant
      higher than those in the controls. The results from our study suggest that the
      higher AGT gene TT genotype and 235T allele frequencies may be risk factors for
      hypertension. High frequencies of the AGT gene 235T allele and high cytokine
      concentrations (IL-1 and TNF-alpha) may promote the transcription and expression
      of AGT, particularly in hypertensive patients with the 235TT genotype.

PMID- 22969921
TI  - TNF-alpha -863 polymorphisms and the risk of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common type of highly malignant tumor.
      Guangxi is an area of China characterized by a high incidence of HCC. Previous
      epidemiological studies have found that chronic infection with hepatitis B virus
      (HBV) is one of the major etiological risk factors for HCC in China. With the
      increased understanding of the host immune response against HBV and the
      pathogenesis of the virus, at present, greater attention is being given to the
      immune response of cytokine genes, as polymorphisms may have a major impact on
      the course and outcome of HBV infection. In the present study, we genotyped tumor
      necrosis factor-alpha (TNF-alpha) rs1800629 (-308G/A), rs1800630 (-863C/A);
      interleukin-1B rs1143627 (-31T/C); and transforming growth factor beta1 (TGF
      beta1) rs1800469 (-509C/T) in a hospital-based study of 772 HCC cases and 852
      cancer-free controls. The distribution of the frequency of TNF-alpha rs1800630
      sites of CC, CA, AA were 65.67, 27.46 and 6.87% in the case group, respectively,
      as compared with 67.02, 29.58 and 3.40% in the controls, all with a statistical
      significance (P<0.05). The logistic regression analysis revealed that the variant
      rs1800630 AA genotypes were associated with a significantly increasing risk of
      HCC (OR=2.058, 95% CI 1.289-3.287), compared with the wild-type rs1800630 CC.
      Further stratified analyses showed that after stratification for history of
      alcohol drinking, in a subgroup of individuals without a history of drinking, the
      HCC risk in the group with the TNF-alpha rs1800630 A allele was 1.839 times
      higher than that in the group with TNF-alpha rs1800630 C (P<0.010). These
      findings suggest that TNF-alpha rs1800630 may contribute to the risk of HCC,
      however, these data require further validation.

PMID- 22969922
TI  - Long-term efficacy of intermittent peritoneal dialysis using various doses.
AB  - The objective of the present study was to investigate the long-term clinical
      efficacy of intermittent peritoneal dialysis (IPD) using various doses and to
      explore the most suitable dialysis dose and practice pattern for patients. A
      total of 52 inpatients/outpatients who had undergone IPD for more than 5 years
      were recruited and divided into three groups according to the dialysis dose: 4
      liters in Group A, 6 liters in Group B and 8 liters in Group C. The dwell time
      was 4 h. All patients were fasted overnight. The dialysis adequacy, nutritional
      status, complication control, blood pressure and intra-abdominal infection were
      determined and observed among these patients. Barthel index (BI) and Hamilton
      Depression Scale (HAMD) were employed to measure the activities of daily living
      (ADL) and degree of depression, respectively. The dialysis adequacy and
      ultrafiltration volume in Group A were lower than those in Groups B and C, but
      the residual urine volume was larger than that in the latter two groups. In
      addition, there was a marked difference in the control of complications between
      Group A and Groups B and C. When compared to Groups A and B, the nutritional
      status in Group C was significantly decreased, the mean arterial pressure and
      intra-abdominal infection rates were dramatically increased, and the HAMD scores
      were also higher (P<0.05). No significant difference was noted in the BI. For
      patients undergoing long-term IPD, individualized dialysis dose may benefit the
      dialysis adequacy, nutritional status, control of complications, blood pressure,
      rate of intra-abdominal infection, ADL and depression.

PMID- 22969924
TI  - Von Willebrand factor, ADAMTS13 activity, TNF-alpha and their relationships in
      patients with chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) often exhibit associated endothelial
      dysfunction and inflammation. Systemic inflammation may contribute to the
      endothelial dysfunction and accelerated thrombosis observed in CKD patients. In
      this study, we assessed the relationships among endothelial dysfunction, a
      disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13
      (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD
      patients were classified into three groups: The chronic glomerulonephritis group
      (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus
      nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis
      factor-alpha (TNF-alpha), von Willebrand factor (VWF) antigen (VWF:Ag) and
      ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal
      controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was
      calculated. The VWF:Ag levels were significantly higher and the ADAMTS13
      activities were significantly lower in the disease groups compared to the
      controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the
      CGN and LN groups (P<0.05). The TNF-alpha levels were higher in the CKD group
      compared to the control group (P<0.01). TNF-alpha was positively correlated with
      the VWF:Ag levels (r=0.242, P=0.013) and negatively correlated with the
      glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was
      negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P=
      0.042). TNF-alpha levels in CKD were positively correlated with the VWF:Ag levels
      and negatively correlated with GFR, which indicates that inflammation may be a
      major cause of endothelial dysfunction and an index of renal function. The VWF:Ag
      levels increased and ADAMTS13 activity decreased in CKD patients, which indicates
      that CKD leads to a prothrombotic state.

PMID- 22969923
TI  - The DNMT3B -579 G>T promoter polymorphism and risk of lung cancer.
AB  - The present study aimed to investigate the association of the -579 G>T
      polymorphism in the DNMT3B promoter with susceptibility to lung cancer. A total
      of 174 lung cancer patients and 135 healthy controls from the northern part of
      China were enrolled, and were matched for gender and age. All subjects were
      genotyped by polymerase chain reaction-restriction-fragment length polymorphism
      analysis and confirmed by DNA sequencing. Stratification analyses were used to
      study the subgroups of subjects by age and gender, and evaluate the association
      between the -579 G>T polymorphism and the genetic susceptibility to lung cancer.
      The results revealed that individuals with the DNMT3B -579 GT genotype had a
      significantly decreased risk of lung cancer [odds ratio (OR), 0.517; 95%
      confidence interval (CI), 0.273-0.981] compared with those with a -579 TT
      genotype in the studied population. However, the deviation was significant (OR,
      0.138, 95% CI, 0.034-0.549) between the risk of lung cancer and the GT and GG
      genotype, when the smoking factor was considered. The data from this study
      indicate that the DNMT3B genetic polymorphism varies among various races, ethnic
      groups and geographical areas. The DNMT3B -579 G>T polymorphism may contribute to
      the genetic susceptibility to lung cancer.

PMID- 22969925
TI  - Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced
      nitric oxide system dysfunction.
AB  - The aim of this study was to assess whether hypoxia inhibits endothelial nitric
      oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether
      iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from
      hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic
      conditions in the absence or presence of 0.1, 10 and 1,000 MUM iptakalim or the
      combination of 10 MUM iptakalim and 1, 10 and 100 MUM glibenclamide for 24 h, and
      the eNOS activity and NO levels were measured in the conditioned medium from the
      HPAEC cultures. The eNOS activity and NO levels were reduced significantly in the
      conditioned medium from HPAEC cultures under hypoxic conditions. Pre-treatment
      with 10 MUM iptakalim normalized the reduction of the eNOS activity and NO levels
      caused by hypoxia in the conditioned medium from HPAEC cultures. Iptakalim raised
      the eNOS activity and NO levels under hypoxic conditions, but was blocked by the
      K(ATP) channel blocker, glibenclamide. Our results indicate that hypoxia impairs
      NO system function, whereas the ATP-sensitive K(+) channel opener, iptakalim, may
      rescue HPAECs from hypoxia-induced NO system dysfunction.

PMID- 22969926
TI  - CREST biorepository for translational studies on malignant mesothelioma, lung
      cancer and other respiratory tract diseases: Informatics infrastructure and
      standardized annotation.
AB  - Advances in molecular epidemiology and translational research have led to the
      need for biospecimen collection. The Cancer of the Respiratory Tract (CREST)
      biorepository is concerned with pleural malignant mesothelioma (MM) and lung
      cancer (LC). The biorepository staff has collected demographic and
      epidemiological data directly from consenting subjects using a structured
      questionnaire, in agreement with The Public Population Project in Genomics
      (P(3)G). Clinical and follow-up data were collected. Sample data were also
      recorded. The architecture is based on a database designed with Microsoft Access.
      Data standardization was carried out to conform with established conventions or
      procedures. As from January 31, 2011, the overall number of recruited subjects
      was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its
      infrastructure, CREST was able to join international projects, sharing samples
      and/or data with other research groups in the field. The data management system
      allows CREST to be involved, through a minimum data set, in the national project
      for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in
      the infrastructure of a pan-European biobank network (BBMRI). The CREST
      biorepository is a valuable tool for translational studies on respiratory tract
      diseases, because of its simple and efficient infrastructure.

PMID- 22969927
TI  - Possibility of molecular targeting therapy for the treatment of cancer of unknown
      primary origin by analysis of intracellular signaling molecules.
AB  - Recently, antibody-mediated epidermal growth factor receptor (EGFR) blockade has
      become a major research focus, and a number of clinical studies on this new
      treatment have been started in the field of clinical oncology. This retrospective
      study investigated the role of KRAS gene mutations and clinical features for
      possibilities for new therapies in patients with cancer of unknown primary (CUP).
      We investigated the role of KRAS, PIK3CA and BRAF gene mutations and clinical
      features for possibilities for new therapies in patients with CUP. Nine patients
      with metastases from an unknown primary tumor were included in this retrospective
      study. The KRAS, BRAF and PI3KCA mutational analyses were carried out by means of
      PCR using genomic DNA for each PCR reaction. The mutation rate in CUP for codon
      12 or 13 of the KRAS gene and for PIK3CA was lower than that in colorectal
      cancer, while the same mutation rate for BRAF was almost the same in the two;
      this means that the EGFR antibodies can possibly treat CUP.

PMID- 22969928
TI  - Expression of human mammaglobin as a marker of bone marrow micrometastasis in
      breast cancer.
AB  - The aim of the present study was to detect the expression of human mammaglobin
      (hMAM) mRNA in the bone marrow (BM) of patients with breast cancer and determine
      the relationship between micrometastasis and clinicopathological parameters as
      well as selected molecular markers and breast cancer prognosis. The expression of
      hMAM mRNA in the BM of patients with breast cancer was determined by RT-PCR. The
      expression of ER, PR and Cath-D in cancer tissues was detected by
      immunohistochemistry. A positive expression rate for hMAM of 38.2% in 102
      patients with stage I-III breast cancer was found. The expression of hMAM was
      higher in patients with T(2-3) (>2 cm) tumors than in those with T(1) tumors (<=2
      cm) (chi(2)=19.20, P=0.001) and in patients with stage II or III tumors than in
      patients with stage I tumors (chi(2)=15.101, P=0.001). The expression of hMAM in
      the BM of breast cancer patients categorized as grade 1 was lower than that in
      those of grade 2 or 3 (chi(2)=8.522, P=0.014), and hMAM expression was related to
      the pathological type of tumor (chi(2)=6.892, P=0.032) and the degree of axillary
      lymph node metastasis (chi(2)=14.050, P=0.001). The expression of hMAM in BM was
      much higher in patients with ER(-) or ER(+) tumors than in those with ER(++ or
      +++) (chi(2)=11.800, P=0.003), and those with PR (chi(2)=8.759, P=0.013). hMAM
      expression in BM was also significantly positively correlated with Cath-D
      expression (chi(2)=6.623, P=0.036). However, no correlation was found between
      hMAM expression and patient age (chi(2)=1.056, P=0.304). There was a strong
      correlation between patients with positive expression of hMAM in the BM and the
      presence of distant metastases (P=0.009). In conclusion, micrometastasis in the
      BM correlates with certain clinical pathological parameters and several tumor
      markers. Patients with positive expression of hMAM in the BM have a greater
      chance of distant metastasis and poor prognosis. The detection of micrometastasis
      may be one of the most advantageous markers for predicting the prognosis of
      breast cancer.

PMID- 22969929
TI  - Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in
      vivo through downregulation of P-gp and LC3-II.
AB  - Traditional Chinese herbal medicines are widely accepted as an option for the
      treatment of colorectal cancers. Danshen (Salviae miltiorrhizae Radix) is widely
      prescribed in traditional Chinese medicine for cardiovascular diseases.
      Tanshinone IIA (Tan-IIA) is extracted from Danshen. Our previous studies have
      shown that Tan-IIA induces apoptosis in Colo205 human colon cancer cells in vitro
      and in vivo. In the present study, we investigated the efficacy of Tan-IIA and 5
      fluorouracil (5-FU) in a Colo205 cell xenograft model. For in vivo studies, SCID
      mice were engrafted with Colo205 cells and from day 10 onwards were randomly
      divided into 3 groups and treated with 5-FU plus Tan-IIA, 5-FU plus corn oil, and
      the vehicle alone. At the end of a 4-week dosing schedule, the SCID mice were
      sacrificed and xenograft tumors were dissected for protein western blot analysis.
      Our results showed that the Colo205 xenograft model co-treated with Tan-IIA plus
      5-FU caused a reduction in the xenograft tumor volumes and decreased P
      glycoprotein (P-gp) and microtubule-associated protein light chain 3 (LC3)-II
      expression compared to 5-FU alone. Based on these observations, it may be
      possible to develop Tan-IIA plus 5-FU as therapeutic agents for human colon
      cancer.

PMID- 22969930
TI  - microRNA-192, -194 and -215 are frequently downregulated in colorectal cancer.
AB  - microRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. They have
      been increasingly shown to have aberrant expression in a number of tumor types.
      miR-192, -194 and -215 have not been comprehensively investigated using a large
      number of cases in colorectal cancer (CRC). We extracted total RNA from 107 CRC
      tissues and three CRC cell lines. Following polyadenylation and reverse
      transcription, the expression levels of miR-192, -194 and -215 were determined
      for evaluation of the association between expression levels and
      clinicopathological characteristics by a quantitative real-time polymerase chain
      reaction (real-time PCR) method. Finally, we studied the impact of miR-194 on
      cell proliferation in HCT-116 cells by MTT assay. miR-192, -194 and -215 were
      significantly downregulated in CRC tissues (all p<0.001, paired t-test) and
      cancer cell lines (all p<0.05) compared to non-tumor counterparts. Moreover, the
      expression levels of miR-192, -194 and -215 were demonstrated to be associated
      with increased tumor sizes (p=0.027, p=0.018, and p=0.027, respectively; Mann
      Whitney U test). Also, there were marked correlations among these miRNAs in CRC
      tissues (all p<0.001, Pearson's regression analysis). Furthermore, we found that
      the overexpression of miR-194 could significantly inhibit cell proliferation in
      HTC-116 cells. miR-192, -194 and -215 may be important biological markers as
      tumor suppressors in the carcinogenesis of CRC.

PMID- 22969931
TI  - Stroke-induced microRNAs: The potential therapeutic role for stroke.
AB  - Stroke is one of the leading causes of death and disability worldwide. In past
      decades, researchers have studied the physiopathology and biochemistry of stroke,
      but knowledge of the molecular mechanisms underlying this disease remains at an
      early stage. To date, only recombinant tissue plasminogen activator (rtPA) has
      been approved by the USA FDA for acute ischemic stroke. However, as the limiting
      therapy time window is 4.5 h after stroke onset and patients must meet the
      applicable conditions, a small number of patients benefit from this therapy.
      Therefore, the research and development of new drugs for stroke are a big
      challenge for scientists. MicroRNAs (miRNAs) are short (20-23 nucleotides) single
      stranded non-coding RNAs. The seed sequences at positions 2-7 from the 5' end
      which are partially or complementary to one or more mRNAs inhibit or degrade
      target mRNAs, thus playing an important role in the post-transcriptional
      regulation of gene expression. Disregulated miRNAs have revealed their complex
      role in pathophysiological processes, and have also shown their potential role in
      disease diagnosis, and use as drug targets in neurodegenerative diseases and
      cancer. Recently, studies have found aberrantly expressed miRNAs in stroke;
      however, the implication of deregulated miRNA expression in stroke remains
      largely unknown. This review briefly summarizes recent studies concerning miRNA
      expression in stroke in vivo and in vitro, focuses on aberrant miRNA expression,
      as well as discusses their potential therapeutic role for stroke.

PMID- 22969932
TI  - Platelets and atherogenesis: Platelet anti-aggregation activity and endothelial
      protection from tomatoes (Solanum lycopersicum L.).
AB  - In recent years, it has been shown that platelets are not only involved in the
      arterial thrombotic process, but also that they play an active role in the
      inflammatory process of atherogenesis from the beginning. The interaction between
      platelets and endothelial cells occurs in two manners: activated platelets unite
      with intact endothelial cells, or platelets in resting adhere to activated
      endothelium. In this context, inhibition of the platelet function
      (adhesion/aggregation) could contribute to the prevention of atherothrombosis,
      the leading cause of cardiovascular morbidity. This can be achieved with
      antiplatelet agents. However, at the public health level, the level of primary
      prevention, a healthy diet has also been shown to exert beneficial effects. Among
      those elements of a healthy diet, the consumption of tomatoes (Solanum
      lycopersicum L.) stands out for its effect on platelet anti-aggregation activity
      and endothelial protection, which may be beneficial for cardiovascular health.
      This article briefly discusses the involvement of platelets in atherogenesis and
      the possible mechanisms of action provided by tomatoes for platelet anti
      aggregation activity and endothelial protection.

PMID- 22969934
TI  - Resveratrol analogue HS-1793 induces the modulation of tumor-derived T cells.
AB  - Recent advances in the understanding of the mechanisms responsible for tumor
      progression suggest the possibility to control cancer growth, not only through
      chemotherapy-induced cancer cell destruction, but also by stimulating anticancer
      immunity. However, immune tolerance against tumor antigens disturbs diverse forms
      of immunotherapy. One of the most potent and well-studied tumor-induced
      immunosuppressive phenotypes found in the tumor microenvironment is the
      regulatory subpopulation cells (CD4(+)CD25(+)FoxP3(+) Treg cells). Among the
      great number of natural agents derived from plants and potentially useful for
      application in the complementary therapy of cancer, resveratrol is gaining
      attention for its immunomodulating properties in breast cancer, since the
      ineffectiveness of numerous immunotherapy strategies may be related, in part, to
      their negative effects on Treg cells. The present study was undertaken to examine
      whether HS-1793, a synthetic resveratrol analogue free from the restriction of
      the metabolic instability and high dose requirement of resveratrol, shows a
      direct effect on immune responses by enhancing lymphocyte proliferation or an
      immunomodulatory effect by inducing changes in the Treg cell population in FM3A
      breast tumor-bearing mice. Although HS-1793 had no direct immunostimulatory
      effect, it dose-dependently decreased IL-2 secretion and increased IL-4 secretion
      of concanavalin A-stimulated lymphocytes from tumor-bearing mice, which suggest
      that HS-1793 may induce changes in the subpopulations of tumor-derived T
      lymphocytes. The CD4(+)CD25(+) cell population from tumor-bearing mice decreased
      after HS-1793 treatment in a dose-dependent manner, while the CD4(+) T cell
      population remained unchanged. FoxP3(+)-expressing cells among the CD4(+)CD25(+)
      population showed a similar pattern. In contrast, the CD8(+) T cell population as
      well as the interferon (IFN)-gamma-expressing CD8(+) T cell population and IFN
      gamma secretion of splenocytes from tumor-bearing mice were significantly
      upregulated by HS-1793 treatment. These results suggest that HS-1793 induces the
      modulation of tumor-derived T lymphocytes, particulary having a suppressive
      effect on the Treg cell population, likely contributing to enhanced tumor
      specific cytotoxic T lymphocyte responses and CD4(+) T cells involving antitumor
      immunity. Therefore, HS-1793 may serve as a promising adjuvant therapeutic
      reagent in breast cancer immunotherapy.

PMID- 22969935
TI  - Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal
      antibody bevacizumab for pancreatic neuroendocrine carcinoma.
AB  - We previously reported that the administration of bevacizumab for pancreatic
      neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor
      growth inhibition. In light of these results, we compared the effect of
      bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The
      QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell
      carcinoma cell line were transplanted into the subcutaneous tissue of mice, and
      the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally
      (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg
      orally five times weekly). The antitumor effect and side effects were evaluated
      by measuring the tumor volume and weight and by changes in body weight,
      respectively. The tumor volume became smaller (from the maximum volume) in the
      group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated
      with bevacizumab and gemcitabine (BG). A significant difference was noted in the
      tumor weight between the BG group and the group treated with bevacizumab alone. A
      relatively significant decrease in the body weight was observed in the BGS and BG
      groups. We conclude that gemcitabine is appropriate as a drug used in combination
      with bevacizumab for pancreatic neuroendocrine tumors.

PMID- 22969933
TI  - Therapeutic strategies for head and neck cancer based on p53 status.
AB  - Squamous cell carcinomas of the head and neck (HNSCC) are one of the most common
      types of cancers worldwide, and despite advances in treatment, they still
      represent a clinical challenge. Inactivation of one or more components in the p53
      signaling pathway is an extremely common event in human neoplasia, including
      HNSCC. The loss of p53 function is responsible for increased aggressiveness in
      cancers, while tumor chemoresistance and radioresistance can depend on deleted
      p53 expression, or on the expression of mutated-p53 proteins. Thus, consideration
      and manipulation of the p53 status during HNSCC cancer therapy should be
      considered. This review discusses the p53 signaling pathways activated by various
      cellular stresses, including exposure to cancer therapies. The recognition of the
      p53 status in cancer cells is a significant factor and could provide valuable
      assistance during the selection of an effective therapeutic approach.

PMID- 22969936
TI  - Increased expression of the prolactin receptor is associated with malignant
      laryngeal tumors.
AB  - The altered expression of the prolactin receptor (PRLR) has been associated with
      the development of various types of cancer, particularly breast, prostate and
      endometrial cancer. However, in laryngeal tumors, the expression of PRLR has not
      yet been documented. The aim of this study was to determine the expression and
      localization of PRLR in laryngeal cancer (LC) in comparison with recurrent
      respiratory papillomatosis (RRP). PRLR expression was analyzed in 48 paraffin
      embedded tissues (18 RRP and 30 laryngeal cancer tissues) by immunoperoxidase
      staining. Furthermore, PRLR expression was evaluated in ten samples from each
      group by Western blot analysis and quantitative real-time PCR. PRLR was observed
      in all laryngeal tumors at different intensities. PRLR overexpression was
      significantly associated (P<0.005) with LC. The staining pattern was homogeneous,
      mainly cytoplasmic, and confined to the tumor area. We found increased expression
      of different isoforms in LC in comparison with RRP. Our results suggest a
      possible role of PRL/PRLR in the development of LC. PRLR may be useful as a
      target for further investigations in laryngeal tissues.

PMID- 22969937
TI  - Synergistic effect of rhein in combination with ampicillin or oxacillin against
      methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for
      a number of infections in humans that are difficult to treat, and as a result, is
      a substantial contributor to morbidity and mortality. In the present study, in
      search of natural products capable of inhibiting this multidrug-resistant
      bacterium, we investigated the antimicrobial activity of rhein isolated from
      Rheum palmatum L. (Polygonaceae) against 16 different strains of the bacterium.
      New antimicrobial activity was found using the paper disc diffusion method
      [minimal inhibitory concentrations (MICs)], MTT test and checkerboard dilution
      test. Against the 16 strains, the disc diffusion test was in the range of 20-29
      mm and the MICs of rhein were in the range of 7.8-31.25 MUg/ml. From these
      results we performed the checkerboard test to determine the synergism of rhein in
      combination with ampicillin (AM) or oxacillin (OX) against all strains. The
      combined activity of rhein and the two antimicrobial agents (AM and OX) against
      all strains resulted in a fractional inhibitory concentration index ranging from
      0.28-1 and from 0.18-1, respectively. The effect of rhein with AM and OX was
      found to be synergistic or partially synergistic. We found that rhein reduced the
      MICs of AM and OX. Rhein in combination with AM or OX could lead to the
      development of new combinations of antibiotics against MRSA infection.

PMID- 22969938
TI  - Aspirin upregulates the expression of neuregulin 1 and survivin after focal
      cerebral ischemia/reperfusion in rats.
AB  - Neuregulin 1 (NGR1) and survivin have been shown to be neuroprotective. However,
      the link between their expression and aspirin in the treatment of cerebral
      ischemia remains unclear. Here, we investigated the effect of aspirin on NGR1 and
      survivin expression after focal cerebral ischemia/reperfusion in rats. Sprague
      Dawley rats were randomly divided into an aspirin treatment group (n=40) and a
      control group (n=40). Each group was further divided into five subgroups
      according to the time after reperfusion. A middle cerebral artery model was
      established by an occlusion suture. At 24 h, 3, 5 and 7 days after reperfusion,
      the Bederson neurological deficit scores were 1.47+/-0.11, 1.22+/-0.08, 0.85+/
      0.15 and 0.59+/-0.12 in the treatment group, and 1.87+/-0.18, 1.45+/-0.14, 1.05+/
      0.08 and 0.75+/-0.15 in the control group, respectively, indicating a significant
      difference at each time point (P<0.05). In the infarct center, the number of NGR1
      and survivin-positive cells reached the maximum at 6 h and decreased gradually
      to a minimum at 7 days, while in the peri-infarct area, the number was few at 6
      h, peaked at 3 days and then was reduced gradually with significant differences
      between the two time points (P<0.05). There were more NGR1- and survivin-positive
      cells in the treatment group compared to the control group (P<0.05). In
      conclusion, the neuroprotective effect of aspirin is at least partly mediated by
      the upregulation of NGR1 and survivin expression after ischemia.

PMID- 22969939
TI  - In vitro effect of adenosine on the mRNA expression of Kir 2.1 and Kir 4.1
      channels in rat retinal Muller cells at elevated hydrostatic pressure.
AB  - The aim of this study was to investigate the expression of Kir 2.1 and Kir 4.1
      channels at an elevated hydrostatic pressure in vitro, and to determine whether
      adenosine may modulate the mRNA expression of Kir 2.1 and Kir 4.1 channels in
      retinal Muller cells at an elevated hydrostatic pressure in vitro. Muller cells
      treated with 1 MUM adenosine at 40 mmHg/24 h, and mRNA expression of Kir 2.1 and
      Kir 4.1 channels were examined using real-time PCR. Muller cells significantly
      increased the mRNA expression of Kir 2.1 and Kir 4.1 channels at 40 mmHg/24 h.
      When further treated with 1 MUM adenosine at 40 mmHg/24 h, the mRNA expression of
      the Kir 2.1 channels decreased, while the mRNA expression of the Kir 4.1 channels
      continued to increase. When the pressure was elevated, Muller cells were still
      able to take up K(+) and mediate the potassium concentration of the retina.
      Adenosine upregulated the expression of the Kir 4.1 channels, but weakly affected
      the expression of the Kir 2.1 channels.

PMID- 22969940
TI  - Osteopontin is overexpressed in colorectal carcinoma and is correlated with P53
      by immunohistochemistry.
AB  - Osteopontin (OPN), a secreted phosphorylated glycoprotein, has been found to be
      involved in carcinogenesis, progression and metastasis of several types of
      cancers. The aim of the present study was to investigate the immunohistochemical
      expression of OPN in colorectal carcinoma (CRC) and its relationship with
      clinicopathological parameters and P53. Expression of OPN, Ki-67 and TP53 was
      detected in 77 cases of CRC by immunohistochemistry and the correlation of the
      expression of OPN with clinicopathological features, Ki-67 and P53 staining was
      investigated. Thirty-eight cases (49.4%) of CRC demonstrated OPN overexpression.
      Overexpression of OPN was associated with lymph node metastasis (P=0.025) and
      Dukes' stages (P=0.031), but not with gender, histological differentiation, depth
      of tumor invasion, TNM stages or Ki-67 index. The correlation between expression
      of OPN and TP53 was statistically significant (P=0.030). In conclusion, OPN is
      overexpressed in CRC, and plays a role in tumor progression and metastasis, which
      is possibly regulated by P53.

PMID- 22969941
TI  - Epigallocatechin-3-gallate decreases UVA-induced HPRT mutations in human skin
      fibroblasts accompanied by increased rates of senescence and apoptosis.
AB  - Our study was designed to determine the protective effect of epigallocatechin-3
      gallate (EGCG) on cultured human skin fibroblasts (HSFs) from multiple
      ultraviolet A (UVA) irradiation-induced hypoxanthine-guanine phosphoribosyl
      transferase (HPRT) mutant colony formation and its underlying mechanisms. In our
      study, the mutation frequency of the HPRT gene was examined by mutagenesis assay.
      Cell senescence was determined by histochemical staining of senescence-associated
      beta-galactosidase. The apoptosis rate was detected by flow cytometry. EGCG
      decreased the UVA-induced HPRT gene mutation frequency by 47.85%. However, EGCG
      further increased the number of senescent cells by 38.92% and the apoptosis rate
      by 56.92% in HSFs. The photo-protective effect of EGCG on multiple UVA-exposed
      HSFs is related to a significant reduction in UVA-induced HPRT mutant cells. This
      may be caused by the induction of damaged cells to proceed to senescence and
      apoptosis.

PMID- 22969942
TI  - Quantitative study of lung perfusion SPECT scanning and pulmonary function
      testing for early radiation-induced lung injury in patients with locally advanced
      non-small cell lung cancer.
AB  - Radiation lung injury is a common side-effect of pulmonary radiotherapy. The aim
      of this study was to quantitatively assess early changes in lung perfusion single
      photon emission computed tomography (SPECT) scanning and pulmonary function
      testing (PFT) prior to and after intensity modulated radiotherapy (IMRT) for
      patients suffering from locally advanced non-small cell lung cancer (LANSCLC).
      Twenty patients with LANSCLC received lung perfusion SPECT scanning and PFT prior
      to IMRT and immediately after IMRT. Lung perfusion index (LPI) was calculated
      after the quantification of perfusion SPECT images. The LPI of the two groups was
      analyzed by matched t-test. The radioactive count of each layer of single lung
      was added to obtain the sum of the irradiated area. The percentage of the
      irradiated area of single lung was calculated. Linear correlation analysis was
      carried out between the percentage of the irradiated area and LPI in order to
      verify the validity of LPI. In this study, LPI and the percentage of the
      irradiated area of single lung exhibited an excellent correlation either prior to
      or after IMRT (r=0.820 and r=0.823, respectively; p<0.001). There was no
      statistically significant difference between pre-IMRT LPI and post-IMRT LPI
      (p=0.135). LPI in the group receiving a radical dose had no statistically
      significant difference (p=0.993), however, it showed a statistically significant
      difference in the group receiving a non-radical dose (p=0.025). In the non
      radical dose group, the post-IMRT LPI was larger compared to pre-IMRT. None of
      the parameters of PFT exhibited a statistically significant difference prior to
      and after IMRT (p>0.05). The quantitative method of lung perfusion SPECT scanning
      can be used to evaluate changes in perfusion early in patients receiving a non
      radical dose (BED <=126,500 cGy) IMRT. Evaluating early changes in global lung
      function using the current method of PFT is difficult, since time can be a
      contributing factor for radiation-induced lung injury.

PMID- 22969943
TI  - Peritumoral lymphatic microvessel density is related to poor prognosis in lung
      adenocarcinoma: A retrospective study of 65 cases.
AB  - Although recent investigations have identified that lymphangiogenesis is
      associated with regional lymph node metastasis and tumor prognosis in non-small
      cell lung cancer (NSCLC), peritumoral lymphatic microvessel density (LMVD) and
      its prognostic significance in lung adenocarcinoma remain unknown. In the present
      study, we assessed peritumoral LMVD in lung adenocarcinoma and investigated its
      correlation with patient prognosis. Using immunohistochemistry (SP method), the
      D2-40-positive peritumoral LMVD count in lung adenocarcinoma was found to be
      11.56+/-10.73, which was higher than intratumoral LMVD (P<0.001), and was found
      to be associated with lymphatic metastasis (P=0.003) and pTNM staging (P=0.046).
      Furthermore, a significant difference in the patient overall survival time was
      demonstrated between tumors with a high peritumoral LMVD and those with a low
      peritumoral LMVD (P=0.005). Finally, using multivariate analysis, it was
      determined that peritumoral LMVD, lymphatic metastasis and pTNM staging were
      independent prognostic factors. In conclusion, the results suggest that D2-40
      positive peritumoral LMVD may predict the prognosis of lung adenocarcinoma.

PMID- 22969944
TI  - Female distance runners show a different response to post-workout consumption of
      wheat gluten hydrolysate compared to their male counterparts.
AB  - Wheat gluten hydrolysate (WGH) is rich in glutamyl residue; glutamine is
      considered a conditionally essential amino acid under physical stress. WGH has
      been reported to suppress post-exercise rises in serum creatine kinase in male
      distance runners. This study aimed to reproduce the effects in female distance
      runners under similar conditions. The study was conducted in a double-blinded
      crossover manner. Six female collegiate distance runners ingested WGH or a
      placebo after a 2-h run at an intensity estimated as 60-70% of their maximum
      oxygen uptake. Blood was sampled before, immediately after, and at 10 and 24 h
      after the run. Unlike those in male runners, serum creatine kinase (CK) increased
      slightly, with a peak at 10 h after the run, while plasma glutamine kept
      declining. The anti-inflammatory effect of WGH was not evident since the post
      exercise elevation of CK was ambiguous. Plasma glutamine concentrations also
      showed a different kinetics from that in men.

PMID- 22969945
TI  - The herbal medicine rikkunshito exhibits strong and differential adsorption
      properties for bile salts.
AB  - Anti-secretory drugs, particularly proton pump inhibitors (PPIs), are the
      preferred treatment agents for patients with gastroesophageal reflux disease
      (GERD). However, refractory GERD, which may manifest as an incomplete or lack of
      response to PPI therapy, is common. Despite the administration of PPIs for
      symptomatic control, duodenogastroesophageal reflux (DGER) containing bile is
      successfully controlled in only one-third of patients. It has previously been
      reported that the traditional Japanese herbal medicine rikkunshito, which has a
      prokinetic action on gastric emptying, exhibits clinically therapeutic effects
      against GERD and DGER that does not respond to PPIs. However, the precise
      mechanisms responsible for the effects of rikkunshito are still unknown. It has
      been suggested that the cytotoxicity of the bile salts in the gut lumen is
      important in GERD and DGER. The aim of the present study was to investigate
      whether rikkunshito is able to adsorb bile salts through the mechanism by which
      it ameliorates the symptoms of GERD and DGER. The binding capacities of
      rikkunshito for bile salts were measured using Langmuir's method. The morphology
      of rikkunshito was also observed by light microscopy. Rikkunshito strongly
      adsorbed bile salts. The binding capabilities of rikkunshito were far beyond
      those of a typical dietary fiber, alpha-cellulose, or an oral adsorbent. In
      addition, rikkunshito had higher binding capacities for hydrophobic bile salts as
      compared with hydrophilic bile salts. In conclusion, rikkunshito has a great
      capacity to adsorb bile salts. This may be part of the mechanism(s) responsible
      for the therapeutic effects of rikkunshito in patients with GERD and DGER.

PMID- 22969946
TI  - Capecitabine combined with (-)-epigallocatechin-3-gallate inhibits angiogenesis
      and tumor growth in nude mice with gastric cancer xenografts.
AB  - Low-dose metronomic chemotherapy represents a new strategy to treat solid tumors
      by exhibiting stronger anti-angiogenic activity and less side effects, especially
      in combination with other anti-angiogenic agents. Capecitabine is a novel
      fluoropyrimidine carbamate, which has a broader spectrum of antitumor activity
      than other fluoropyrimidines, such as 5-FU, DFUR or UFT; it has proved effective
      over a wide dose range. The aim of this study was to investigate the anti
      angiogenic effect of capecitabine alone and combined with the angiogenic
      inhibitor (-)-epigallocatechin-3-gallate (EGCG) on gastric cancer. A BGC-823
      human gastric cancer xenograft model was used, and tumor growth, side effects and
      the number of days of survival of mice were closely monitored and recorded.
      Quantitative real-time PCR was used to determine vascular endothelial growth
      factor (VEGF) mRNA levels. The expression of VEGF and CD31 was determined by
      immunohistochemistry. Our results indicated that metronomic capecitabine
      inhibited angiogenesis, growth of gastric cancer and improved survival with less
      toxicity, and the effects were further enhanced by the concurrent administration
      of EGCG. Clinical trials and further pre-clinical studies, will hopefully provide
      answers to the use of continuous low-dose anti-angiogenic therapies for the
      treatment of human gastric cancer.

PMID- 22969948
TI  - Survival and risk of relapse of acute lymphoblastic leukemia in a Mexican
      population is affected by dihydrofolate reductase gene polymorphisms.
AB  - Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key
      component in childhood acute lymphoblastic leukemia (ALL) treatment.
      Polymorphisms in the gene coding for DHFR have been associated with adverse event
      treatment. This study evaluated the effect of the -A317G and C829T polymorphisms
      in the DHFR gene on survival and risk of relapse of ALL. Seventy patients with
      ALL and 100 healthy individuals were genotyped by the polymerase chain reaction
      restriction fragment length polymorphism method. An association between the
      polymorphisms and the risk of relapse was found (p<0.05); patients with the 
      317G/G genotype were found to have an 8.55 (95% CI 1.84-39.70) higher chance of
      relapse and carriers of the 829T/T genotype had a 14.0 (95% CI 1.13-172.63)
      higher chance of relapse. Other variables, such as age and leukocyte count, were
      associated (p<0.05) with the risk of relapse of the disease. Individuals with the
      G/G and T/T genotype of the -A317G and C829T polymorphisms had poorer survival
      compared to other genotype groups (log-rank test; p<0.05). Although preliminary,
      these data seem to suggest a role for the DHFR polymorphisms in the risk of
      relapse of ALL and the mortality risk in these patients.

PMID- 22969947
TI  - Association between IL6 -174G/C and cancer: A meta-analysis of 105,482
      individuals.
AB  - Interleukin-6 (IL6) is a pleiotropic inflammatory cytokine, which is implicated
      in the development and progression of several types of cancer. The -174G/C
      polymorphism of the IL6 gene controls serum levels of IL6 and may be associated
      with cancer risk, but the results from the published studies on the association
      between this polymorphism and cancer risk are conflicting. A comprehensive meta
      analysis was conducted to assess the association of IL6 -174G/C with cancer risk.
      Studies were identified by searches of MEDLINE and HuGE Published Literature
      databases, with no restrictions. An eligible 83 articles involving 44,735 cancer
      patients and 60,747 controls were included. Combined odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to assess the strength of the association
      between the IL6 -174 G/C polymorphism and cancer risk. Potential sources of
      heterogeneity were explored by meta-regression and sensitivity analysis. Overall,
      the IL6 -174G/C polymorphism was not significantly associated with cancer risk.
      However, cancer risk was increased for individuals with the CC genotype compared
      to those carrying the GG genotype in African populations (OR=1.83, 95% CI 1.26
      2.67, P=0.002), but not in Caucasian populations (OR=1.00, 95% CI 0.92-1.08,
      P=0.938). The present meta-analysis provides the first evidence of the ethnic
      specific association of the IL6 -174G/C polymorphism with cancer risk. Further
      investigations with a large number of cases and controls are required to confirm
      the associations between this polymorphism and cancer in Africans.

PMID- 22969949
TI  - Correlation of polymorphisms of the vascular endothelial growth factor gene and
      the risk of lung cancer in an ethnic Han group of North China.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic mediator. The
      present study investigated the relationship between genetic polymorphisms of VEGF
      and susceptibility to lung cancer in a Han ethnic group of North China. The
      genotypes in the -2578C and 936C loci of VEGF gene were determined using PCR-RFLP
      method in 150 patients with lung cancers and 150 healthy individuals. Software
      PHASE 1.0 was used to analyze the experimental data. The non-conditional logistic
      regression model was used to analyze the statistical association of genotypes and
      susceptibility in the two groups adjusted by multiple factors. VEGF polymorphisms
      were found to be a critical risk for the genetic susceptibility to lung cancers
      in the ethnic Han group of North China. SNP polymorphisms at the -2578C and 936C
      loci of the VEGF gene were detected by the RFLP-PCR method. High rates of a
      single-base C-to-A alteration at the -2578 locus and high rates of a single-base
      C-to-T alteration at the 936 locus of both alleles were correlated with the
      occurrence of lung cancer. The SNP markers at the -2578C and 936C loci of the
      VEGF gene may serve as biological markers of lung cancer.

PMID- 22969950
TI  - Global dysregulation of the chromosome 14q32 imprinted region in uterine
      carcinosarcoma.
AB  - Uterine carcinosarcoma (UCS) is a rare but very aggressive cancer of the female
      reproductive tract with an extremely poor prognosis. With the goal of
      understanding the role of microRNA (miRNA) dysregulation in these tumors, we
      profiled the expression of 667 human miRNAs in a panel of eight UCS patients and
      five benign control primary tissue samples. These expression profiles revealed
      two important characteristics of UCS. First, compared with the two most common
      uterine cancers, endometrial endometrioid adenocarcinoma and endometrial serous
      adenocarcinoma, UCS samples display a virtually unique pattern of miRNA
      dysregulation with an overlap of only 5% among the three tumor types. In
      addition, nearly one-third of the miRNAs significantly dysregulated in UCS
      tissues compared with benign endometrium (32 of 114) lie in a single small (250
      kb) imprinted region of chromosome 14q32. These data suggest that the presence of
      such a global, region-specific disruption substantially contributes to the unique
      histology and poor outcome of this type of cancer.

PMID- 22969951
TI  - Transcervical intrauterine levobupivacaine infusion or paracervical block for
      pain control during endometrial biopsy.
AB  - The aim of this study was to determine pain during endometrial biopsy by
      comparing the use of intrauterine instillation of levobupivacaine or paracervical
      block with a placebo in a randomized, double-masked trial in premenopausal and
      postmenopausal women. A total of 90 women were enrolled in the study. Patients
      were allocated to either the control or case groups. Group 1 consisted of 30
      cases with intrauterine anesthesia with 5 ml 0.5% levobupivacaine. Group 2
      consisted of 30 patients who underwent paracervical block with lidocaine. No
      analgesic agent was given to the remaining 30 patients; these cases comprised the
      control group. The primary outcome measures were pain or discomfort experienced
      during the procedure. When the pain scores of the different groups were compared,
      the scores in the intrauterine levobupivacaine and paracervical block groups were
      found to be significantly lower compared to those in the control group. There was
      no difference between the levobupivacaine and paracervical block groups in terms
      of pain scores. There was a marked positive correlation between biopsy
      indications and pain scores. Pain scores were lower in cases with the indication
      of polymenorrhea, hypermenorrhea and metrorraghia compared to those in the cases
      with other indications. In conclusion, the transcervical intrauterine
      instillation of levobupivacaine or paracervical block with lidocaine brings about
      pain relief during and after endometrial biopsy.

PMID- 22969952
TI  - A polymorphism at the miR-502 binding site in the 3' untranslated region of the
      SET8 gene is associated with the outcome of small-cell lung cancer.
AB  - microRNAs (miRNAs) bind to the 3' untranslated regions (UTRs) of messenger RNAs,
      where they interfere with translation of genes that regulate cell
      differentiation, apoptosis and tumourigenesis. The histone methyltransferase SET8
      has been reported to methylate TP53 and regulate genomic stability. We analysed a
      single nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region
      at the 3' UTR of SET8 in small-cell lung cancer (SCLC) patients. The SET8 CC+CT
      genotype was identified to be independently associated with longer survival in
      SCLC patients by multivariate analysis (relative risk, 0.453; 95% CI 0.217-0.944;
      p=0.035). The analysis of genetic polymorphisms in miRNA binding sites may help
      to identify patient subgroups at high risk of poor outcome.

PMID- 22969953
TI  - Korean red ginseng protects against neuronal damage induced by transient focal
      ischemia in rats.
AB  - In the present study, we investigated the neuroprotective effect of Korean red
      ginseng (KRG) following focal brain ischemia/reperfusion injury, in relation to
      its antioxidant activities. The middle cerebral artery occlusion/reperfusion
      (MCAO/R) model in rats was employed. The KRG extract (100 mg/kg, perorally) was
      administered once daily for 7 days following MCAO/R. The elevated levels of lipid
      peroxidation in the MCAO/R group were attenuated significantly in the KRG
      administered group. The significantly depleted activity of the antioxidant
      enzymes glutathione peroxidase, superoxide dismutase and catalase was prevented
      in the KRG-administered group. In the neurobehavioral evaluation expressed as the
      modified neurological severity score and corner-turn test, the daily intake of
      KRG showed consistent and significant improvement in the neurological deficits
      for 7 days following MCAO/R injury. These results indicate that KRG has a
      neuroprotective effect against ischemia/reperfusion brain injury by reducing the
      level of lipid peroxidation and increasing the endogenous antioxidant enzymatic
      activity.

PMID- 22969954
TI  - Long-term survival of patients with hepatocellular carcinoma with pulmonary and
      adrenal metastasis: A case report.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the
      liver, and has a poor prognosis. In this study, we reported an exceptional
      clinical case of primary HCC with metastatic disease in the lungs 1 year
      following hepatic resection, and in the left adrenal gland 8 years following
      hepatic resection. Comprehensive treatments, including partial hepatic resection,
      systemic chemotherapies with various regimens, such as radiotherapy, were
      administered to this patient. In this case, there was no intrahepatic recurrence
      of the malignancy and the metastatic disease was sensitive to chemotherapy and
      radiotherapy. The patient remained alive and in good health for 10 years
      following the diagnosis of HCC despite early metastatic disease. This indicates
      that for certain patients with advanced stage HCC, palliative treatments may
      still be beneficial to their survival. We also discussed the advance in recent
      research into HCC treatment.

PMID- 22969955
TI  - Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1
      gene on childhood IgA nephropathy.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of the
      fibrinolytic pathway and extracellular matrix (ECM) turnover. The -675 4G/5G
      polymorphism in the PAI-1 promoter is associated with altered PAI-1
      transcription, suggesting that this polymorphism may be a candidate risk factor
      for diseases characterized by ECM accumulation, such as immunoglobulin A
      nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MesPGN). We
      genotyped childhood patients with biopsy-confirmed IgAN (n=111) and MesPGN
      (n=47), and healthy control subjects (n=230) for the -675 4G/5G PAI-1
      polymorphism by polymerase chain reaction-restriction fragment length
      polymorphism methods. The distribution of the 4G/4G (27.9%), 4G/5G (45.1%) and
      5G/5G (27.0%) genotypes in IgAN patients was significantly different from the
      healthy controls (32.2, 54.3 and 13.5%, respectively) (p=0.0092). There was no
      significant difference in the genotype distributions of the 4G/5G polymorphism
      between MesPGN patients and the healthy controls. Regarding the impact of the
      polymorphism on IgAN, the 4G/4G genotype was markedly increased in patients with
      proteinuria (>=1,000 mg/day) and/or hypertension when compared to patients
      without proteinuria and hypertension (OR=5.23, 95% CI 1.34-20.38, P=0.0183).
      These findings indicate that the PAI-1 gene polymorphism may affect the
      susceptibility of childhood IgAN.

PMID- 22969957
TI  - Connective tissue growth factor gene expression and decline in renal function in
      lupus nephritis.
AB  - In lupus nephritis (LN), kidney inflammation may be followed by fibrosis and
      progressive decline in function. Transforming growth factor (TGF)-beta is a
      notable mediator of fibrosis, but it has other beneficial roles, thus indicating
      a need for alternate therapeutic targets for inhibition of fibrosis. Connective
      tissue growth factor (CTGF) acts as a downstream mediator of TGF-beta in
      promoting fibrosis, without mediating the immunosuppressive effects of TGF-beta.
      Animal studies show that CTGF may have important roles in renal fibrosis, but
      data are limited in human subjects. The present study tested the hypothesis that
      renal CTGF mRNA expression is related to TGF-beta1 and collagen I expression and
      is predictive of renal function deterioration in patients with LN (n=39). Gene
      expression was measured using multiplex real-time quantitative RT-PCR and renal
      function was estimated using the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) glomerular filtration rate (GFR) equation. Decline in GFR
      was assessed by regression of GFR at biopsy to 1 year following biopsy. CTGF mRNA
      expression was significantly correlated with TGF-beta1 and collagen I. GFR at
      biopsy was 89.2+/-39.2 ml/ min. Renal CTGF mRNA expression correlated inversely
      with baseline GFR. Renal CTGF mRNA was significantly higher in patients with
      moderate to severe CKD compared to those in the milder CKD group (low GFR 4.92+/
      4.34 vs. high GFR 1.52+/-1.94, p<0.005). CTGF mRNA was also higher in patients
      with subsequent decline in GFR [GFR decline (5.19+/-4.46) vs. no GFR decline
      (1.79+/-1.97); P<0.01]. In conclusion, renal expression of CTGF was positively
      related to TGF-beta1 and collagen I in patients with LN. Furthermore, high CTGF
      mRNA expression was associated with poor GFR at baseline and subsequent
      deterioration of kidney function. CTGF expression in the kidney may serve as an
      early marker for renal disease progression and could be evaluated as a target for
      therapeutic intervention to prevent renal failure in LN.

PMID- 22969956
TI  - Beneficial effect of dietary Ephedra sinica on obesity and glucose intolerance in
      high-fat diet-fed mice.
AB  - Obesity is a major contributor to both glucose intolerance and metabolic
      syndrome. In this study, we investigated the anti-obesity and anti-hyperglycemic
      effects of Ephedra sinica on high-fat diet-fed mice. Male ICR mice were divided
      into four groups; the normal group, the obese and diabetic control group treated
      with a high-fat diet, the positive control group treated with a high-fat diet
      containing acarbose, and the experimental group treated with a high-fat diet
      containing Ephedra sinica. The effects of Ephedra sinica on obesity and glucose
      intolerance were measured by an oral glucose tolerance test (OGTT), plasma
      biochemistry, body and epididymal fat weight; the expression of adiponectin,
      peroxisome-proliferator-activated receptor alpha (PPAR-alpha), tumor necrosis
      factor alpha (TNF-alpha) and leptin was also determined. Ephedra sinica reduced
      weight gain and epididymal fat accumulation, improved glucose intolerance on the
      OGTT, decreased triglycerides and increased high-density lipoprotein cholesterol
      compared to the controls. Moreover, it reduced weight gain and fasting glucose
      levels and improved HDL-cholesterol levels more than acarbose. Gene expression
      analysis revealed that Ephedra sinica upregulated the expression of adiponectin
      and PPAR-alpha, and downregulated the expression of TNF-alpha. From these
      results, we suggest that Ephedra sinica may reduce obesity and hyperglycemia by
      increasing PPAR-alpha and adiponectin and reducing TNF-alpha, and that it may
      have the potential to be used clinically as an ingredient in food or drugs
      effective in obesity-related glucose intolerance treatments.

PMID- 22969958
TI  - Genetic polymorphisms in key DNA repair genes and risk of head and neck cancer in
      a Chinese population.
AB  - Although tobacco and alcohol consumption are the major risk factors of head and
      neck cancer (HNC), genetic variations of genes involved in several biological
      pathways, such as DNA repair genes, may affect an individual's susceptibility to
      HNC. However, few studies have investigated the associations between
      polymorphisms in DNA repair genes and HNC risk in the Chinese population. Thus,
      we genotyped five common, non-synonymous single-nucleotide polymorphisms (SNPs)
      [APEX1 (Asp148Glu), XRCC1 (Arg399Gln), ADPRT (Val762Ala), XPD (Lys751Gln) and XPG
      (His1104Asp)] in a hospital-based, case-control study of 397 HNC cases and 900
      cancer-free controls in China. The results showed that none of the five SNPs in
      the DNA repair pathway was significantly associated with HNC risk, suggesting
      that these polymorphisms may not play a major role in HNC susceptibility in this
      Chinese population.

PMID- 22969959
TI  - Short-term outcomes of CyberKnife therapy for advanced high-risk tumors: A report
      of 160 cases.
AB  - The objective of the present study was to evaluate short-term outcomes of
      CyberKnife therapy in patients with advanced high-risk tumors. A total of 201
      target areas from 341 advanced high-risk tumor lesions in 160 patients were
      treated with CyberKnife. A prescribed dose of 18-60 Gy to the gross tumor volume
      was delivered in 1-6 fractions to complete the entire treatment in 1 week.
      Radiographic studies and clinical examinations were performed at 1- to 3-month
      follow-up intervals, and the results were compared to outcomes of 160 similar
      advanced high-risk tumor patients who were treated by conformal radiotherapy
      (CRT). After CyberKnife therapy, the short-term improvement in the quality of
      life was significant according to radiographic study, radioimmunoassay and ZPS
      scores of these patients. The total rates of objective efficacy and alleviation
      of ascities were as high as 66.88 and 67.90%. The short-term outcomes in our
      series of patients with advanced high-risk tumors treated with CyberKnife
      appeared to be better compared to conventional CRT. CyberKnife may be an option
      for patients with incurable advanced high-risk tumors, although further studies
      of the long-term outcomes are required to confirm the validity.

PMID- 22969960
TI  - Prognostic role of telomerase activity in gastric adenocarcinoma: A meta
      analysis.
AB  - Activation of telomerase is involved in carcinogenesis in most types of cancers.
      However, the prognostic value of telomerase activity (TA) in patients with
      gastric carcinoma (GC) remains controversial. We conducted a meta-analysis to
      assess the relationship between TA and the clinical outcome of GC. A meta
      analysis of 18 studies (886 patients) was performed to evaluate the association
      between TA and metastasis-related parameters in GC patients by searching
      databases, including PubMed, MEDLINE, EMBASE, Web of Science databases, Cochrane
      Library and the Chinese Biomedical Literature database (CBM) (last search updated
      in October 2011). We used the odds ratios (ORs) with 95% confidence intervals
      (CIs) to assess the strength of the association between TA and metastasis of GC.
      Our analysis results indicated that high telomerase activity expression tended to
      be associated with the presence of lymph node metastasis (866 patients) (OR=2.03,
      95% CI 1.21-3.39, p=0.007), the depth of invasion (886 patients) (OR=1.87, 95% CI
      1.30-2.70, p=0.0007), distant metastasis (407 patients) (OR=2.71, 95% CI 1.59
      4.63, p=0.0002), tumor size (466 patients) (OR=2.14, 95% CI 1.31-3.50, p=0.002)
      and TNM stage (711 patients) (OR=2.39, 95% CI 1.30-4.41, p=0.005). However, high
      TA expression was not associated with the presence of histologic differentiation
      (791 patients) (OR=1.51, 95% CI 0.73-3.11, p=0.26). In conclusion, telomerase
      overexpression not only plays a key role in primary initiation, but also promotes
      invasion and metastatic progression of GC. These findings raise the possibility
      of using TA to screen for the prognosis of gastric cancer.

PMID- 22969961
TI  - Potent anti-inflammatory agent escin does not affect the healing of tibia
      fracture and abdominal wound in an animal model.
AB  - Escin, a potent anti-inflammatory and anti-edematous agent, has been widely used
      clinically in preventing inflammatory edema after trauma, such as fracture and
      surgery. The aim of this study was to investigate whether escin has an inhibitory
      effect on fracture healing, and whether escin has an inhibitory effect on wound
      healing after surgery. Male New Zealand white rabbits underwent tibial mid
      diaphyseal osteotomy, and were administered escin once per day for 10 days. At
      weeks 2, 4 and 6, bone fracture healing and bone mineral density were measured.
      The histologic examination of callus, osteocalcin, alkaline phosphatase, calcium
      and phosphate in the serum were also assayed. In another experiment, the rats
      underwent midline laparotomy, and received escin once prior to or after the
      operation. Six days later, the abdominal incision wounds were excised for
      measuring hydroxyproline levels. The results showed that there were no
      significant differences in fracture healing between the model and rabbits
      administered escin, and escin did not affect the hydroxyproline levels in the
      abdominal incision wounds of the rats. These findings suggest that escin has no
      inhibitory effect on fracture and wound healing in animal models.

PMID- 22969962
TI  - Association between subclinical hypothyroidism and Sasang constitution in a
      Korean population.
AB  - Serum thyroid-stimulating hormone screening of asymptomatic individuals to
      diagnose subclinical hypothyroidism remains controversial. We evaluated the
      potential role of Sasang constitutional discrimination and ryodoraku testing as
      an alternative and complementary diagnostic tool for subclinical hypothyroidism.
      Among 1,105 potential subjects, 1,073 were included in this study. Of these, 134
      subjects had subclinical hypothyroidism (SCH) and 939 were healthy (euthyroid;
      EU) control subjects. Blood parameters, including serum thyroid hormone levels,
      were measured. We classified the participants into the four Sasang constitutional
      types, Taeyang-type individuals, Taeeum-type individuals, Soyang-type individuals
      and Soeum-type individuals, and measured their ryodoraku scores (RS). The mean
      levels of free thyroxine (FT4), glucose, red blood cells and hematocrit in the
      SCH group were significantly lower compared to those in the EU group (p<0.0183,
      p=0.0006, p=0.0162 and p=0.0224, respectively). The mean FT4 level of the Soeum
      type SCH patients was significantly lower compared to the Soeum-type EU patients
      (p=0.0423). The total RS was significantly higher in the Taeeum-type SCH patients
      (p=0.0253) and lower in the Soeum-type SCH patients (p=0.0094) compared to
      controls. Ryodoraku testing and Sasang constitutional discrimination have the
      potential to serve as alternative and complementary diagnostic tools for
      subclinical hypothyroidism.

PMID- 22969963
TI  - Correlation between MTA2 overexpression and tumour progression in esophageal
      squamous cell carcinoma.
AB  - The aim of this study was to clarify the clinicopathological outcome and
      prognostic significance of metastasis-associated gene 2 (MTA2) in esophageal
      squamous cell carcinoma (ESCC). Immunohistochemical staining for MTA2 was
      performed on surgical specimens obtained from 162 patients with ESCC.
      Relationships between MTA2 expression and clinicopathological factors, including
      prognosis, were analyzed. Significant correlations were noted among MTA2
      overexpression and TNM clinical classification staging, depth of invasion,
      presence of regional lymph node metastasis, presence of distant metastasis,
      lymphatic invasion, blood-vessel invasion and the 5-year survival rates. The
      expression of MTA2 protein was correlated with tumour progression. Patients with
      MTA2 overexpression tended to have poor prognosis compared to patients with MTA2
      underexpression.

PMID- 22969964
TI  - Combination therapy using oral S-1 and targeted agents against human tumor
      xenografts in nude mice.
AB  - In this study, combination therapies using the oral fluoropyrimidine tegafur
      gimeracil-oteracil (S-1) with several targeted agents or antibodies, were
      evaluated. First, the effects of tyrosine kinase inhibitors (erlotinib
      hydrochloride, sorafenib tosilate and sunitinib malate) against human non-small
      cell lung cancer (NSCLC), breast cancer and colorectal cancer were evaluated in
      vivo. The effects of the combination of S-1 and targeted antibodies (bevacizumab
      and cetuximab) against human colorectal cancers was also evaluated in vivo. S-1
      and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,
      erlotinib, showed a significant inhibition of growth in human NSCLC (Lu-99 and PC
      9 cell lines). The antitumor activity of the combination of S-1 and erlotinib
      against Lu-99 and PC-9 cancer cell lines was significantly superior to either
      monotherapy (P<0.05). Combination therapy using the multi-tyrosine kinase
      inhibitors, sorafenib or sunitinib, with S-1 against breast cancer (MX-1 cell
      line) and NSCLC (NCI-H460 cell line) was significantly superior to either
      monotherapy (P<0.01). The combination of the anti-vascular endothelial growth
      factor antibody bevacizumab or the anti-EGFR antibody, cetuximab, with S-1
      against human colorectal cancer [Col-1, KM20C (bevacizumab) and DLD-1 (cetuximab)
      cell lines] and a 5-fluorouracil (5-FU)-resistant cell line (KM12C/5-FU) was
      significantly superior to either monotherapy (p<0.01). In particular, the growth
      of the Col-1 cells was completely inhibited by the combination of S-1 and
      bevacizumab. No toxic mortalities and no significant difference in the body
      weight changes of the animals treated with S-1 combined with the targeted agents
      or with the mono-therapies were observed; therefore, the treatments appeared to
      be well-tolerated. Our preclinical findings indicate that the combination
      therapies of S-1 and targeted agents are promising treatment options.

PMID- 22969965
TI  - Clinical and prognostic significance of miR-155 and miR-146a expression levels in
      formalin-fixed/paraffin-embedded tissue of patients with diffuse large B-cell
      lymphoma.
AB  - It has been found that aberrant expression of microRNAs (miRNAs) is strongly
      associated with carcinogenesis. In the present study, we investigated the
      expression of miR-155 and miR-146a in diffuse large B-cell lymphoma (DLBCL)
      patients (n=90). The expression levels of miR-155 and miR-146a were significantly
      higher in de novo DLBCL patients. miR-146a expression levels were associated with
      miR-155, lactate dehydrogenase, beta 2 microglobulin, c-myc, International
      Prognostic Index status and Eastern Cooperative Oncology Group performance
      status. We found that patients with low miR-155 and miR-146a expression levels
      achieved a higher complete remission rate, higher overall response rate and
      longer progression-free survival time. Moreover, a high expression level of miR
      155, but not miR-146a, was an independent indicator for chemotherapy protocol
      selection in our study. Patients with high expression of miR-155 received more
      survival benefits from rituximab treatment. These data suggest that miR-155 and
      miR-146a have potential as diagnostic and prognostic markers in DLBCL.

PMID- 22969966
TI  - Braf and erbB2 mutations correlate with smoking status in lung cancer patients.
AB  - The erbB pathway involves a family of tyrosine kinases and contributes to
      resistance or sensitivity to chemotherapy in many tumor types. Somatic mutations
      of the epidermal growth factor receptor (EGFR) gene at the kinase domain have
      been found in lung cancer patients. These mutations are correlated with clinical
      response to targeted molecular therapy. Although Caucasian lung cancer patients
      have been shown to harbor Braf and erbB2 mutations, only a few reports exist
      concerning Braf and erbB2 mutations in Japanese lung cancer patients. We
      investigated the Braf and erbB2 mutation status in non-small cell lung cancer
      (NSCLC) patients by reverse transcription-polymerase chain reaction (RT-PCR) and
      direct sequencing. The study included 305 surgically removed lung cancer samples
      from the Nagoya City University Hospital, which were EGFR and Kras wild-type
      centric. Six Braf mutations were found in the adenocarcinoma cases. Among the
      adenocarcinoma cases, Braf mutations were more frequently noted in heavy smokers
      (Brinkman index >400, p=0.0476). We also detected five erbB2 mutations all in the
      non-smokers. All of these mutations existed exclusively. The erbB2 gene mutations
      were predominantly found in non-smokers with adenocarcinomas. However, the
      completely exclusive mutation status could help us design individually tailored
      targeted molecular therapy for lung cancer.

PMID- 22969967
TI  - Interferon-gamma enhances promyelocytic leukemia protein expression in acute
      promyelocytic cells and cooperates with all-trans-retinoic acid to induce
      maturation of NB4 and NB4-R1 cells.
AB  - In order to investigate the effect and mechanisms of interferon (IFN)-gamma in
      combination with all-trans-retinoic acid (ATRA) on NB4 cells [ATRA-sensitive
      acute promyelocytic leukemia (APL) cell line] and NB4-R1 cells (ATRA-resistant
      APL cell line) and to search for a novel approach to solve the problem of ATRA
      resistance in APL, we initially treated NB4 and NB4-R1 cells with IFN-gamma, ATRA
      and IFN-gamma in combination with ATRA, respectively. The cell proliferation was
      then tested by MTT assay, and the cell differentiation was tested through light
      microscopy, by NBT test and flow cytometry (FCM). The expression of promyelocytic
      leukemia (PML) protein was observed by indirect immune fluorescent test. Results
      showed that ATRA inhibited the growth of NB4 cells, however, it could not inhibit
      the growth of NB4-R1 cells. IFN-gamma inhibited the growth of both NB4 and NB4-R1
      cells. Meanwhile, the growth inhibition effect of IFN-gamma in combination with
      ATRA on both NB4 and NB4-R1 cells was significantly stronger than that of any
      single drug treatment. The results of the NBT reduction test and CD11b antigen
      detection by FCM indicated that IFN-gamma induces the differentiation of NB4 and
      NB4-R1 cells to some extent. Moreover, the maturation degree of both NB4 and NB4
      R1 cells induced by IFN-gamma in combination with ATRA was more significant than
      that of IFN-gamma or ATRA alone. After treatment with IFN-gamma, the number of
      fluorescent particles in NB4 and NB4-R1 cell nuclei was higher than those in the
      control group, which indicated that IFN-gamma may induce the expression of PML
      protein. Together, IFN-gamma augments the proliferation inhibition effect of ATRA
      on NB4 and NB4-R1 cells through enhancing the expression of PML protein. IFN
      gamma in combination with ATRA not only strengthens the induction differentiation
      effect of ATRA on NB4 cells, but also can partially induce the maturation of NB4
      R1 cells with ATRA resistance.

PMID- 22969968
TI  - Curative propensity of green tea extract towards hepatic fibrosis induced by
      CCl(4): A histopathological study.
AB  - Hepatic fibrosis constitutes a serious insult to the liver, with a substantial
      negative impact on the quality of life of such patients worldwide. It is a
      consequence of severe liver damage and occurs as the result of several factors.
      Chronic alcoholism is the most common cause. Fibrosis also results from chronic
      viral hepatitis and autoimmune hepatitis. Prolonged exposure to environmental
      toxins such as carbon tetrachloride (CCl(4)) can also lead to fibrosis. In the
      present study, the hepato-protective effects of green tea extract (GTE) on
      hepatic fibrosis in a rat liver CCl(4)-induced fibrosis model were examined
      histologically, 3-dimensionally and biochemically. GTE was prepared from dried
      green tea leaves and lyophilized. Male albino rats (n=20) weighing 200-250 g were
      divided into four groups: GI, control; GII, administered 50 mg/kg GTE dissolved
      in physiological saline daily for four weeks; GIII, administered 40% CCl(4) (1
      ml/kg body weight) by subcutaneous injection daily for four weeks; and GIV,
      treated as GIII, followed by 50 mg/kg GTE dissolved in physiological saline daily
      for 4 weeks. Histology and 3-dimensional scanning electron microscopy showed
      hepatic fibrosis with intermingled fibers located between cells in the liver
      tissues of the CCl(4)-treated rats. Fibrotic lesions virtually disappeared after
      four weeks of treatment with GTE, returning the architecture of liver tissue back
      to its normal state. Also, the levels of the hepatic enzymes alanine
      aminotranferase and aspartate aminotransferase returned to their normal levels
      after treatment with GTE. The rats were found to regain their normal body weight
      and their fur color, which had faded due to weight loss. The autopsy results
      showed the animal liver returning to normal shape and color. Thus, green tea
      extract is a potent treatment for hepatic fibrosis caused by CCl(4) in this
      animal model.

PMID- 22969969
TI  - Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for
      resectable pancreatic cancer.
AB  - Results of surgery alone for pancreatic cancer are disappointing. We
      retrospectively evaluated the efficacy and tolerability of neoadjuvant
      chemotherapy (NAC) with gemcitabine and oral S-1 in patients with potentially
      resectable pancreatic cancer. A total of 34 patients with pancreatic ductal
      adenocarcinoma, radiologically diagnosed preoperatively as having potentially
      resectable tumors, underwent pancreatic resection with lymphadenectomy at
      Kanazawa University Hospital. NAC was administered to 13 patients (NAC group).
      The remaining 21 patients were surgically treated without preoperative
      chemotherapy (control group). Surgical results were compared between these two
      groups, with follow-up for at least 24 months. No statistically significant
      differences were found in the clinicopathological background data (tumor
      location, age, gender, lymph node metastases, tumor stage and tumor size) between
      the NAC and control groups. Following preoperative chemotherapy, no patients were
      judged to be unable to undergo laparotomy, i.e., neither distant metastasis nor
      tumor progression was observed. Radiologically, all 13 NAC group patients had
      stable disease, whereas, histopathologically, all tumor specimens showed evidence
      of tumor cells. The treatment effect was judged by Evans grading to be grade IIa
      in 11 patients and grade IIb in 2 patients. Toxicity was evaluated in 11
      patients. Grade III side effects were regarded as hematological toxicity, i.e.,
      leucopenia (7.7%) and thrombocytopenia (15.4%). Moreover, the incidence of
      perioperative complications did not differ significantly between the NAC and
      control groups. The one- and three-year overall survival rates of the NAC group
      with pancreatic head cancer were 88.9 and 55.6%, respectively, superior to 88.9
      and 29.6% in the control group (p=0.055). Therefore, NAC with gemcitabine and S-1
      is well tolerated and potentially effective against pancreatic head cancer. A
      phase I study of NAC with gemcitabine and S-1 is under way in patients with
      resectable pancreatic cancer.

PMID- 22969970
TI  - Overexpression of the miR-34 family suppresses invasive growth of malignant
      melanoma with the wild-type p53 gene.
AB  - Malignant melanoma is the most aggressive neoplasm, with severe metastatic
      potential. microRNAs represent a class of endogenously expressed, small non
      coding RNAs that regulate gene expression. As a consequence, the translation of
      these mRNAs is inhibited or they are destabilized resulting in downregulation of
      the encoded protein. The microRNA-34 (miR-34) family, which comprises three
      processed microRNAs (miR-34a/b/c) was identified as the mediator of tumor
      suppression by p53. Many reports suggest that the miR-34s contribute to the
      inhibition of invasion or metastasis in various tumor types. In this study, we
      evaluated the expression of the miR-34 family in four human melanoma cell lines
      (A375, G361, C32TG and SK-MEL-24) which have the wild-type p53 gene using real
      time reverse transcription PCR. We also examined their generative and invasive
      characteristics using the cell proliferation assay and the invasion/migration
      assay, respectively. All four melanoma cell lines showed significant expression
      of miR-34s - A375: miR-34a 0.6176, miR-34b 0.7625, miR-34c 0.7877; G361: 7.6424,
      16.4127, 22.0332; C32TG: 2.1630, 2.1091, 8.4425; SK-MEL-24: 0.3621, 2.5659,
      8.5907. The cell doubling times of these cell lines in h:min were as follows:
      A375 23:23, G361 68:24, C32TG 47:22 and SK-MEL-24 67:03. The in vitro generation
      times of G361 and SK-MEL-24, which showed increased expression of miR-34c, were
      significantly shorter than A375 with decreased expression of miR-34c (p=0.0063,
      ANOVA). Invasion (%) of the four cell lines was as follows: A375 44.0%, G361
      22.4%, C32TG 13.8% and SK-MEL-24 45.0%. In vitro invasiveness of G361 and C32TG,
      which showed increased expression of miR-34a, was significantly suppressed (p=
      0.005, ANOVA). These results suggest that overexpression of miR-34a and c
      suppresses invasive and generative potentials, respectively, in human malignant
      melanoma.

PMID- 22969971
TI  - Clinical significance of immunohistochemical expression of insulin-like growth
      factor-1 receptor and matrix metalloproteinase-7 in resected non-small cell lung
      cancer.
AB  - Insulin-like growth factor-1 receptor (IGF-1R) and matrix metalloproteinase-7
      (MMP-7) have been reported to be related to tumor invasion and metastasis in
      various malignancies. The aim of this study was to evaluate the expression levels
      of IGF-1R and MMP-7 in resected non-small cell lung cancer (NSCLC) and to examine
      the relationship of such levels to clinical characteristics and survival.
      Expression was measured immunohistochemically. The percentage of stained cells
      was multiplied by the staining intensity. The sample was classified as high when
      the score was equal or higher than the median value or was otherwise considered
      to be low. High IGF-1R expression was associated with nodal metastasis and
      recurrence (P=0.034 and 0.006, respectively). High IGF-1R expression was
      associated with significantly poorer overall survival than low IGF-1R expression
      (P=0.011). MMP-7 expression did not significantly correlate with any
      clinicopathological factor. There was a trend toward slightly, but not
      significantly poorer survival in patients with MMP-7-high tumors than in those
      with MMP-7-low tumors (P=0.220). There was no significant correlation between IGF
      1R expression and MMP-7 expression (P=0.184). Upon multivariate analysis, IGF-1R
      expression was independently related to the outcomes of patients with NSCLC.
      Overexpression of IGF-1R may be a useful predictor of lymph node metastasis,
      recurrence and post-surgical outcomes in patients with NSCLC.

PMID- 22969972
TI  - Effect of A(2A) receptor antagonist (SCH 442416) on the mRNA expression of
      glutamate aspartate transporter and glutamine synthetase in rat retinal Muller
      cells under hypoxic conditions in vitro.
AB  - The purpose of the present study was to investigate the effect of the A(2A)
      receptor antagonist (SCH 442416) on the mRNA expression of glutamate aspartate
      transporter (GLAST) and glutamine synthetase (GS) in rat retinal Muller cells
      under hypoxic conditions in vitro. Immunofluorescent staining of GS and GFAP was
      used for the identification of Muller cells. The GLAST and GS mRNA expression of
      Muller cells treated with 0.1, 1 and 10 MUM SCH 442416 under hypoxic conditions
      was examined by real-time PCR. Muller cells increased the mRNA expression of
      GLAST under hypoxic conditions; those treated with 0.1 MUM SCH 442416 showed a
      further significant increase in the mRNA expression of GLAST in vitro. Although
      the mRNA expression of GS was decreased under hypoxic conditions, the mRNA
      expression was increased when Muller cells were treated with 0.1 MUM SCH 442416.
      A(2A) receptor antagonist increased the GLAST and GS expression of Muller cells
      and accelerated the clearance of extracellular glutamate under hypoxic conditions
      in vitro.

PMID- 22969973
TI  - Investigation of wound healing in rat lung tissues in the postpartum period.
AB  - To assess the wound healing capabilities of damaged lung tissue in the postpartum
      period, we investigated the parameters related to wound healing in a rat model of
      lung damage. Rats were divided into six groups: IA, IB, II, IIIA, IIIB and IV
      (n=7 in each group). Group IA included rats not in the postpartum period that
      were sacrificed on the third day after lung injury, group IB included rats not in
      the postpartum period that were sacrificed on the tenth day after lung injury,
      group II included rats not in the postpartum period that did not receive lung
      injury, group IIIA included rats in the postpartum period that were sacrificed on
      the third day after lung injury, group IIIB included rats in the postpartum
      period that were sacrificed on the tenth day after lung injury and group IV
      included rats in the postpartum period without lung injury. Wound healing was
      evaluated histopathologically and measurements of hydroxyproline levels, serum
      alanine and glutamine were taken. A significant difference in serum alanine
      levels was evident between groups IA and IIIA. Significant differences were also
      observed between serum alanine and glutamine levels in groups IB and IIIB. In
      conclusion, we demonstrated that serum alanine levels were reduced in the
      postpartum period following lung injury, which may be expected to negatively
      impact wound healing in this period. The administration of exogenous alanine for
      traumatic events occurring during the postpartum period may thus contribute
      positively to wound healing capabilities during this period.

PMID- 22969974
TI  - CD44 is associated with tumor recurrence and is an independent poor prognostic
      factor for patients with localized clear cell renal cell carcinoma after
      nephrectomy.
AB  - CD44 has been implicated in tumor development and progression in several types of
      cancer. CD44 expression is altered in renal cell carcinoma (RCC) and has been
      suggested as a useful prognostic marker, but its prognostic role in RCC remains
      controversial. We investigated the expression of CD44 in a large homogeneous set
      of localized clear cell RCC to determine its potential prognostic value. We
      examined 110 patients with localized clear cell RCC who underwent nephrectomy.
      The clinicopathological data were obtained retrospectively and the expression
      level of CD44 was studied by immunohistochemistry. Correlations between CD44
      expression and clinical parameters as well as survival were determined. The CD44
      high expression group (HEG) was significantly associated with a higher nuclear
      grade (P=0.014) and tumor recurrence (P<0.001) when compared with the CD44-low
      expression group (LEG). Concerning survival, the 5-year recurrence-free survival
      (RFS) rates for the CD44-HEG and CD44-LEG groups were 38.9 and 91.3%,
      respectively (P<0.001), and the 5-year disease-specific survival (DSS) rates for
      the CD44-HEG and CD44-LEG groups were 55.6 and 94.6%, respectively (P<0.001).
      Multivariate analyses showed that CD44 expression [hazard ratio (HR), 9.204;
      P<0.001] was an independent risk factor predicting RFS in patients with clear
      cell RCC. CD44 expression remained an independent prognostic factor for DSS
      (P=0.002). In conclusion, these data indicate that CD44 expression is associated
      with the progression of clear cell RCC and is an independent poor prognostic
      factor for tumor recurrence and survival, suggesting that CD44 may serve as a
      useful molecular marker.

PMID- 22969975
TI  - Sodium aescinate ameliorates liver injury induced by methyl parathion in rats.
AB  - Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural
      pest control for several years. The present study investigated the protective
      effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury
      induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided
      into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg)
      poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg
      groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and
      acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and
      antioxidative parameters were measured. Histopathological examination of the
      liver was also performed. The results revealed that SA had no effect on AChE.
      Treatment with SA decreased the activities of ALT and AST, and the levels of
      malondialdehyde and NO. Treatment with SA also increased the level of glutathione
      and the activities of superoxide dismutase and glutathione peroxidase. SA
      administration also ameliorated liver injury induced by methyl parathion
      poisoning. The findings indicate that SA protects against liver injury induced by
      methyl parathion and that the mechanism of action is related to the antioxidative
      and anti-inflammatory effects of SA.

PMID- 22969976
TI  - Special nutrition in mouse developmental oocytes.
AB  - Investigation of nutrition-related proteins in mouse oocytes and zygotes is
      crucial for the development of an effective therapy for patients with
      infertility. Currently, we are concerned with the role of nutrition in the
      process of oocyte development in order to better reveal the relationship between
      nutrition and infertility. We collected mouse oocytes at three different
      developmental stages: germinal vesicle (GV) stage, metaphase II-arrested (MII)
      stage and fertilized oocytes (zygotes). Semi-quantitative mass spectrometry and
      GeneMapper software were used to analyze nutrition-related proteins in these
      oocytes. Various specific proteins were abundantly expressed in the mouse
      oocytes. These proteins included heat shock proteins and Ybx2. Additional
      proteins which exist in important meta bolism pathways also demonstrated
      differential expression among the three stages. We identified additional
      nutrition elements required for oocyte development and fertilization. The present
      study contributed to increased understanding of nutrition in the process of
      oocyte development, which may enhance the efficacy of therapy for patients with
      infertility.

PMID- 22969977
TI  - Lack of prognostic relevance of Her-2/neu, topoisomerase IIalpha and EGFR in
      advanced ovarian carcinoma.
AB  - Patients with advanced ovarian cancer (FIGO stage III) have a poor clinical
      prognosis. However, these patients show distinct differences in their survival
      time, possibly due to differing responses to chemotherapy and differing tumor
      biology. In contrast to histological subtype, grading and staging, which are
      known to affect a patient's prognosis, the impact of the human epidermal growth
      factor receptor 2 (Her-2/neu), topoisomerase IIalpha and epidermal growth factor
      receptor (EGFR) on survival remain inconclusive. Therefore, the aim of this study
      was to assess their impact on survival in a group of advanced ovarian cancer
      patients. Tissue microarrays were constructed from specimens of 243 patients.
      Gene copy and chromosome numbers were evaluated by fluorescence in situ
      hybridization (FISH) and protein expression by immunohistochemistry (IHC).
      Scoring for the latter was calculated by considering the percentage of positive
      tumor cells and the relative staining intensity. FISH results were evaluated by
      previously published recommendations and correlated with overall survival. Using
      IHC, 1.6% of the cases that were tested for Her-2/neu and topoisomerase IIalpha
      were strongly positive, and 12.3% were positive for EGFR. Using FISH, 4.4%
      amplifications and 2.1% polysomies for Her-2/neu were identified; topoisomerase
      IIalpha showed 2.2% amplifications, 0.4% deletions and 3.5% polysomies. We
      observed 10.8% high polysomies, but no amplification for EGFR. None of the
      results obtained by IHC or FISH correlated with overall survival. In general, Her
      2/neu, topoisomerase IIalpha and EGFR may be prognostic factors in ovarian
      carcinomas. However, within this group of FIGO stage III patients, differences in
      gene aberration or protein expression were not able to predict differences in
      survival.

PMID- 22969978
TI  - Competing causes of death in patients with oropharyngeal cancer treated with
      radiotherapy.
AB  - Radiation with or without chemotherapy is considered the mainstay of treatment
      for the majority of patients with oropharyngeal cancer. The goal of this study
      was to analyze competing causes of mortality in patients with oropharyngeal
      cancer with long-term follow-up. We queried the Surveillance, Epidemiology and
      End Results (SEER) database and identified 3728 patients with oropharyngeal
      cancer treated between 1988 and 2001 with definitive radiotherapy. We analyzed
      predictors of overall survival and risks of mortality from index oropharyngeal
      cancer, second primary cancer, cardiovascular disease and other causes using a
      cumulative incidence analysis and Cox multivariate analysis. With a median follow
      up of 6.8 years, the 5- and 10-year overall survival was 37 and 22%,
      respectively. At 5 years, the risk of mortality from primary oropharyngeal cancer
      was 35%. Between years 3 and 10, 69% of mortalities were attributed to causes
      other than the index cancer. Despite advances in the non-surgical treatment of
      oropharyngeal cancer, patients remain at significant risk of cancer- and non
      cancer-related mortality.

PMID- 22969980
TI  - Polyethylene glycol 4000 treatment for children with constipation: A randomized
      comparative multicenter study.
AB  - The aim of this study was to evaluate the efficacy and safety of polyethylene
      glycol 4000 (PEG 4000) for the treatment of constipation in children over 8 years
      of age. A total of 216 children from 7 hospitals were enrolled. A total of 105
      patients received oral PEG 4000 (20 g/day) and 111 patients received oral
      lactulose (15 ml/day) for 2 weeks. The stool frequency, stool consistency and
      abdominal pain of the patients were monitored. In the PEG group, following one
      week and two weeks of treatment, the median weekly stool frequency improved from
      2 times prior to treatment to 6 and 7 times, respectively, following treatment.
      The clinical remission rates of the PEG and lactulose groups following one week
      of treatment were 70.48 and 39.64%, respectively, and following two weeks of
      treatment were 72.38 and 41.44%, respectively. Abdominal pain disappeared in
      74.6% of patients following two weeks of PEG 4000 treatment. No significant
      clinical adverse effects or abnormalities in the laboratory tests were observed
      in the two treatment groups. In conclusion, PEG 4000 is a safe and more effective
      drug compared to lactulose for the treatment of constipation in children.

PMID- 22969979
TI  - Zoledronate inhibits phosphate and bone morphogenetic protein 2-induced
      extracellular calcification of vascular smooth muscle cells in vitro.
AB  - The aim of this study was to explore the effects of the bisphosphonate
      zoledronate on calcification induced by inorganic phosphate (Pi) and/or bone
      morphogenetic protein 2 (BMP-2) and the underlying mechanisms. Primary vascular
      smooth muscle cells (VSMCs) from rats were treated with 3 mM Pi or 3 mM Pi/BMP-2,
      with and without addition of zoledronate; 1.4 mM Pi served as a control. Calcium
      deposits, expression of core binding factor alpha-1 (Cbfa-1), osteopontin (OPN),
      parathyroid pituitary-specific transcription factor (Pit)-1 and Pit-2, and Pi
      uptake of VSMCs was determined. The calcification of VSMCs induced by elevated Pi
      or Pi/BMP-2 was significantly inhibited by zoledronate. The expression of Cbfa-1,
      OPN and Pit-1 was increased significantly after treatment with an elevated level
      of Pi or Pi/BMP-2, and this expression was significantly suppressed by addition
      of zoledronate. Pi uptake of VSMCs increased following treatment with elevated Pi
      and significantly decreased by addition of zoledronate. These results indicated
      that zoledronate effectively inhibited calcification induced by Pi/BMP-2, and
      this may have been achieved by means of the downregulation of expression of
      calcification-related proteins and uptake of Pi.

PMID- 22969981
TI  - Comparative proteomic analysis of secreted proteins from nasopharyngeal carcinoma
      associated stromal fibroblasts and normal fibroblasts.
AB  - Since the concept of the secretome (ensemble of proteins secreted and/or shed
      from cells) was proposed, it has become an attractive and challenging proteomic
      technology in recent years. However, secretome analysis still faces some
      difficulties mainly related to sample collection and preparation. In the present
      study, we established a reliable method for extracting secreted proteins by
      ultrafiltration centrifugation and conducting secretomic analysis. Accumulating
      evidence suggests that carcinoma-associated stromal fibroblasts (CAFs) play an
      important role in cancer initiation and progression. To investigate the
      expression patterns of secreted proteins from fibroblasts and to identify the
      secreted proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, we
      conducted comparative secretome analysis between CAFs and normal fibroblasts.
      After two-dimensional gel electrophoresis (2-D PAGE), 11 significant spots were
      differentially expressed and identified by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). These
      proteins may take part in the regulation of the tumor micro-environment through
      different processes. The expression level of galectin-1 in the CAF supernatant
      was also determined by ELISA. This study provides useful information and new
      clues for the further understanding of the regulatory mechanisms of CAFs in the
      NPC microenvironment.

PMID- 22969982
TI  - Sequence polymorphisms of the mitochondrial displacement loop and outcome of non
      small cell lung cancer.
AB  - Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop
      (D-loop) of mitochondrial DNA (mtDNA) may be associated with disease outcome. Our
      team investigated the prediction power of D-loop SNPs in non-small cell lung
      cancer (NSCLC) outcome. In an overall multivariate analysis, allele 16390 was
      identified as an independent predictor for NSCLC outcome. The length of survival
      of patients with allele 16390A was significantly shorter than that of patients
      with allele 16390G (relative risk, 0.323; 95% CI, 0.109-0.951; p=0.040). The
      analysis of genetic polymorphisms in the mitochondrial D-loop can help identify
      NSCLC patient subgroups at a high risk for a poor disease outcome.

PMID- 22969983
TI  - Development of a new auxiliary heterotopic partial liver transplantation
      technique using a liver cirrhosis model in minipigs: Preliminary report of eight
      transplants.
AB  - This study aimed to develop a new auxiliary heterotopic partial liver
      transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis.
      Based on our previous study, 14 minipigs were induced to cirrhosis by
      administration of carbon tetrachloride (CCl(4)) through intraperitoneal
      injection. All of the cirrhotic animals were utilized as recipients. The donor's
      liver was placed on the recipient's splenic bed, and the anastomosis was
      performed as follows: end-to-end anastomosis between the donor's portal vein and
      the recipient's splenic vein, end-to-side anastomosis between the donor's
      suprahepatic vena cava and the recipient's suprahepatic vena cava, and end-to-end
      anastomosis between the donor's hepatic artery and the recipient's splenic
      artery. The common bile duct of the donor was intubated and bile was collected
      with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic
      venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored
      throughout the transplantation. All 8 minipigs that developed liver cirrhosis
      were utilized to establish the new AHPLT; 7 cases survived. Following the
      surgical intervention, the PVP and PVPG of the recipients were lower than those
      prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased
      significantly compared to those of the normal animals (P<0.05). A new operative
      technique for AHPLT has been successfully described herein using a model of liver
      cirrhosis.

PMID- 22969984
TI  - Use of cetuximab in combination with pulsed reduced dose-rate radiotherapy in a
      patient with recurrence of nasopharyngeal carcinoma in the neck.
AB  - Reirradiation is a major therapeutic modality for patients with locally recurrent
      head and neck carcinoma. Due to normal tissue tolerances, reirradiation using
      conventional techniques has a narrow therapeutic ratio in the regional recurrence
      of nasopharyngeal carcinoma (NPC). Pulsed reduced dose-rate radiotherapy (PRDR),
      which delivers a series of 0.2 Gy pulses separated by 3 min intervals, is a new
      reirradiation technique. Head and neck carcinoma cells have high levels of
      epidermal growth factor receptor expression and cetuximab shows a clear benefit
      to locally advanced head and neck carcinoma. We report a 56-year-old male with a
      recurrent lesion of NPC in the neck following initial radical radiochemotherapy.
      The patient was retreated with PRDR and concurrent cetuximab. The total dose of
      PRDR was 70 Gy, using 35 daily fractions of 2.0 Gy. The recurrent lesion of this
      patient had a complete response with no apparent radiation-induced normal tissue
      complications. This is the first study concerning PRDR combined with cetuximab
      for the treatment of recurrent head and neck carcinoma following radiotherapy.
      The outcome of this patient reveals that treatment with PRDR and concurrent
      cetuximab is a promising therapeutic option for patients with recurrent head and
      neck carcinoma following radiotherapy.

PMID- 22969985
TI  - Decrease in Fas-induced apoptosis by the gamma-secretase inhibitor is dependent
      on p75(NTR) in a glioblastoma cell line.
AB  - p75(NTR), a member of the tumor necrosis factor superfamily, plays a key role in
      numerous physiological processes, including cell survival or apoptosis. Yet, the
      associated signaling pathways remain poorly understood. Similar to Notch, gamma
      secretase cleavage is implicated in the p75(NTR) signaling pathway leading to
      nuclear translocation of the intracellular domain and cell death. Fas receptor
      activation was found to promote cell death apoptosis in several cell lines. The
      goal of this study was to determine the respective role of p75(NTR) and Notch in
      the resistance to Fas-induced apoptosis in the U-87 MG glioblastoma cell line.
      Using the gamma-secretase inhibitor, we investigated the modulation of Fas
      induced apoptosis dependent on p75(NTR)-Fas receptor interaction. Whereas the U
      87 MG cells expressed the Fas receptor at the cell membrane, apoptosis induced by
      Fas activation was decreased by the gamma-secretase inhibitor. These data suggest
      that gamma-secretase is implicated in p75(NTR) and Fas interaction leading to
      cell death signaling.

PMID- 22969986
TI  - DNA sequencing of TGFbeta2 in sporadic patients with tetralogy of Fallot.
AB  - Transforming growth factor beta2 (TGFbeta2) plays an essential role in cardiac
      morphogenesis. However, the prevalence of TGFbeta2 mutations in congenital heart
      disease (CHAD) and the correlation between the TGFbeta2 genotype and the CHAD
      phenotype have not been studied extensively. The aim of this study was to examine
      DNA sequence changes in the TGFbeta2 gene in sporadic patients with tetralogy of
      Fallot (TOF), and to observe whether TGFbeta2 is the susceptibility gene for TOF.
      A cohort of 100 pediatric patients with TOF was recruited to the study; 200
      healthy children were used as controls. PCR and genotyping were conducted for the
      detection of DNA changes in TGFbeta2. The exons and the 5' untranslated region
      (5'UTR) sequences of the TGFbeta2 gene were amplified. No mutations were
      identified in the coding region in any of the TOF patients. However, three single
      nucleotide changes, including 9126 A>AC, 9353 A>AG and 9040_9043 del CTTC, in the
      5'UTR were found. There were no significant differences in allelic frequencies
      and genotype frequencies of position 9126 and 9353 between the TOF group and the
      control group. On the contrary, a significant difference was identified in the
      allelic frequencies (chi(2)=17.469, P<0.001) of position 9040_9043 in the 5'UTR
      between the TOF group and the control group. Our results suggest that TGFbeta2
      may be a potential candidate gene of TOF. SNPs at position 9040_9043 del CTTC in
      the 5'UTR of TGFbeta2 may be associated with susceptibility to TOF. The CTTC
      allele may be the susceptibility allele for TOF. However, the exact effect of
      these sequence changes requires further study using functional experiments.

PMID- 22969987
TI  - Association study between polymorphisms of the PARD3 gene and schizophrenia.
AB  - The aim of this study was to investigate whether par-3 partitioning defective 3
      homolog (C. elegans) (PARD3) single nucleotide polymorphisms (SNPs) are
      associated with schizophrenia. A total of 204 Korean schizophrenic patients [117
      male, 41.1+/-9.6 years (mean age +/- SD); 87 female, 42.6+/-11.5] and 351 control
      subjects (170 male, 43.8+/-6.6 years; 181 female, 44.2+/-5.8) were enrolled. We
      genotyped nine SNPs of the PARD3 gene [rs7075263 (intron), rs10827392 (intron),
      rs773970 (intron), rs2252655 (intron), rs10763984 (intron), rs3781128
      (Ser889Ser), rs1936429 (intron), rs671228 (intron) and rs16935163 (intron)].
      Genotypes of PARD3 polymorphisms were evaluated by direct sequencing. We used
      SNPStats, SPSS 18.0 and Haploview 4.2 software for analysis of genetic data.
      Multiple logistic regression models were used to calculate the odds ratio (OR),
      95% confidence interval (CI), and corresponding p-values (p), controlling for age
      and gender as covariables. Allele frequencies of the PARD3 SNPs were
      significantly associated with schizophrenia (rs3781128, p=0.041; rs1936429,
      p=0.030; rs671228, p=0.028). Certain genotype frequencies of the PARD3 SNPs also
      showed significant associations with schizophrenia (p<0.05, rs7075263, rs773970,
      rs2252655, rs10763984, rs3781128, rs1936429, rs16935163). To the best of our
      knowledge, this is the first report showing that PARD3 is associated with
      susceptibility to schizophrenia in a Korean population. In conclusion, our
      findings suggest that PARD3 may contribute to genetic susceptibility to
      schizophrenia.

PMID- 22969988
TI  - Video-assisted thoracoscopic surgery versus open lobectomy for stage I lung
      cancer: A meta-analysis of long-term outcomes.
AB  - The present study aimed to evaluate the evidence comparing video-assisted
      thoracoscopic surgery (VATS) and open lobectomy for the treatment of stage I lung
      cancer using meta-analytical techniques. A literature search was undertaken until
      July 2011 to identify comparative studies evaluating survival rates, recurrence
      rates and complications. Pooled odds ratios (OR) and 95% confidence intervals
      (95% CI) were calculated with either the fixed- or random-effects model. These
      studies included a total of 1,362 patients: 668 treated with VATS and 694 treated
      with open lobectomy. The overall survival was significantly higher in patients
      treated with VATS than with open thoracotomy (OR=2.01, 95% CI 1.44-2.78) at 5
      years. However, there was no statistically significant difference in 1.3-year
      overall survival between the VATS and open lobectomy groups (OR=3.21, 95% CI 0.77
      13.40; OR=0.91, 95% CI 0.49-1.70). The data did not demonstrate a significant
      difference in locoregional recurrence (OR=0.58, 95% CI 0.33-1.03) compared to the
      open lobectomy group, but suggested a reduced systemic recurrence rate (OR=0.52,
      95% CI 0.23-0.82) and complications (OR=0.36, 95% CI 0.23-0.57) of VATS. VATS was
      superior to open lobectomy for the prognosis of stage I lung cancer. However, the
      findings have to be carefully interpreted due to the lower levels of evidence.

PMID- 22969989
TI  - Tumor necrosis factor-alpha -308G/A polymorphism is associated with active
      vitiligo vulgaris in a northeastern Mexican population.
AB  - Vitiligo is a skin disease characterized by depigmentation. Its etiopathogenesis
      is unclear, but it has been associated with autoimmune processes. Gene
      polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) have been associated
      with several imflammatory diseases. In particular, the -308G/A polymorphism in
      the gene promoter region has been reported to be associated with increased plasma
      levels of TNF-alpha and with an increased risk to develop autoimmune diseases. To
      date, this polymorphism has not been associated with vitiligo. To assess a
      possible association between the TNF-alpha -308G/A and vitiligo vulgaris (VV),
      198 vitiligo patients and 395 control subjects were recruited for the study. A
      complete demographic and clinical profile of each case was registered to analyze
      the possible risk factors of vitiligo. Genomic DNA isolated from peri pheral
      blood was subjected to PCR-RFLP for genotyping of the TNF-alpha -308G/A
      polymorphism. Causal associations were determined by chi(2) test and their
      respective OR was assessed in a 2*2 contingency table. When population variables
      of type of vitiligo, gender, age of disease onset, and active disease status were
      considered, an association between active VV and the TNF-alpha GA genotype was
      found (P=0.0295, OR=2.0; 95% CI 1.01-3.93). All other variables were irrelevant
      to vitiligo. Our data suggest a possible association between the TNF-alpha -308
      GA genotype and the active form of VV in a Mexican population.

PMID- 22969990
TI  - Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high
      dose interleukin-2 for metastatic melanoma: The surgeon's perspective.
AB  - Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and
      growing and expanding ex vivo large quantities of autologous T cells. Once the
      TILs are ready for infusion, the patient undergoes a non-myeloablative lympho
      depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus
      IL-2. This study reviews the surgical experience of the TIL program at the Chaim
      Sheba Cancer Research Center in Israel. Eligible patients underwent surgical
      consultation to determine what tumorectomy would be beneficial for harvesting
      appropriate tissue. Factors involved in the decision included tumor mass size,
      location and morbidity of the procedure. Between January 2006 and May 2010, 44
      patients underwent 47 procedures of adoptive transfer of TILs. Three patients
      underwent the procedure twice for recurrence after initial good responses,
      including an additional surgical procedure to produce fresh tumor. Thirty-seven
      excisions were with general anesthesia and 10 were with local anesthesia. Of the
      37 general anesthesia procedures, 27 were open procedures involving a
      thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used
      minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy
      sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung
      specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical
      mortality and major morbidity was 0%. Minor morbidity included only wound
      complications. Maximal number of TILs were derived from lymph node specimens,
      while liver metastasis procured the fewest TILs. Adoptive cell transfer
      technology affords a maximal tumor response with minimal surgical morbidity in
      metastatic patients.

PMID- 22969991
TI  - Folate receptor-mediated targeted polymeric gadolinium complexes for magnetic
      resonance imaging in pulmonary tumor xenografts.
AB  - Targeted delivery is a highly desirable strategy for diagnostic imaging due to
      enhanced efficacy and reduced dosage/toxicity. The need to develop target
      specific magnetic resonance imaging (MRI) contrast agents to aid in disease
      characterization is highly essential. In this study, a specific contrast agent,
      Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its
      efficacy as a targeted agent for the imaging of tumors that overexpress the
      folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the epsilon-amino
      groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in
      cultured tumor cells that overexpressed the folate receptor. The tumor-selecting
      properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing
      subcutaneously implanted folate receptor-positive tumors. Tissue MR signal
      intensities were measured at six different time-points. In the in vitro study,
      the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the
      folate receptor, as with free folic acid. Excellent tumor selectivity was also
      shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a
      maximum intensity increase of 125.4% was observed from pre-injection compared to
      post-injection images of the tumor at the 48 h time-point. The liver enhancement
      was non-specific and the muscle signal intensity at any time-point after
      injection showed no statistical difference with that observed before injection.
      Folate-PL-Gd-DTPA is a promising, novel receptor-specific MRI contrast agent with
      potential applications in the imaging of human folate receptor-positive tumors.

PMID- 22969992
TI  - Effects of apelin and leptin on renal functions following renal
      ischemia/reperfusion: An experimental study.
AB  - The present study aimed to investigate the effects of apelin and leptin on renal
      functions following renal ischemia/reperfusion (I/R). A total of 32 rats were
      divided into four groups. The control group was not induced with ischemia, but
      was administered normal saline intraperitoneally. Normal saline, apelin and
      leptin were administered intraperitoneally to the I/R, ischemia/reperfusion and
      apelin (I/R+A) and ischemia/reperfusion and leptin (I/R+L) groups, in turn for
      three days prior to the surgical procedure. Blood and urine samples were obtained
      after 24 h of reperfusion, and scintigraphic examination was performed. Renal
      damage was evaluated histopathologically. Urea levels of the I/R+L and I/R+A
      groups were comparable, but were higher compared to that of the control group.
      The I/R group had the highest urea levels (control, 27+/-2; I/R, 120+/-15; I/R+A,
      75+/-10; I/R+L, 80+/-11; p<0.001). Creatinine levels were higher in all three
      ischemic groups compared to the control group. Glomerular filtration rate values
      of the I/R+A and I/R+L groups were not significantly, but numerically higher
      compared to that of the I/R group. No pathological damage was observed in any of
      the animals in the control group. In the I/R group, two animals had moderate and
      six had severe renal damage, while three had moderate and one had severe renal
      damage in the I/R+L group. In the I/R+A group, moderate renal damage was found in
      one animal, while none had severe renal damage. This study demonstrates the
      functional and histopathological protective effects of leptin and apelin against
      renal I/R injury.

PMID- 22969993
TI  - Prunella vulgaris aqueous extract attenuates IL-1beta-induced apoptosis and NF
      kappaB activation in INS-1 cells.
AB  - We previously reported that Prunella vulgaris aqueous extract (PVAE) promotes
      hepatic glycogen synthesis and decreases postprandial hyperglycemia in ICR mice.
      Inflammatory cytokines play a critical role in the pathogenesis of diabetes. This
      study was designed to examine whether PVAE has a protective effect on IL-1beta
      induced apoptosis in INS-1 cells. INS-1 pancreatic beta cells were plated at
      2*10(6)/ml and treated with PVAE (100 ug/ml) 30 min before the cells were
      challenged with IL-1beta (10 ng/ml). Untreated INS-1 cells served as control. INS
      1 cell cytotoxicity was examined by MTT and lactate dehydrogenase (LDH) activity
      assays. Caspase-3 activity and activation of the apoptotic signaling pathway were
      analyzed by western blotting. NF-kappaB binding activity was examined by EMSA.
      The levels of inflammatory cytokines in the supernatant were measured by ELISA.
      IL-1beta treatment significantly induced INS-1 cell death by 49.2%, increased LDH
      activity by 1.5-fold and caspase-3 activity by 7.6-fold, respectively, compared
      with control cells. However, PVAE administration significantly prevented IL-1beta
      increased INS-1 cell death and LDH activity and attenuated IL-1beta-increased
      caspase-3 activity. Western blot data showed that PVAE also significantly
      attenuated IL-1beta-increased Fas, FasL and phospho-JNK levels in the INS-1
      cells. In addition, PVAE treatment significantly attenuated IL-1beta-increased NF
      kappaB binding activity and prevented IL-1beta-increased TNF-alpha and IL-6
      expression in INS-1 cells. Our data suggest that PVAE has a protective effect on
      IL-1beta-induced INS-1 cell apoptosis. PVAE also attenuates IL-1beta-increased NF
      kappaB binding activity and inflammatory cytokine expression in INS-1 cells. PVAE
      may have a benefit for type I diabetic patients.

PMID- 22969994
TI  - Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for
      gastric cancer and expression of MHC class I.
AB  - Protein-bound polysaccharide K (PSK) is a glycoprotein that is purified from the
      mushroom Coriolus versicolor. In Japan, PSK is clinically used in combination
      with anticancer agents following gastric cancer surgery. Evaluation of the
      response is difficult, as efficacy is determined via antitumor immunoenhancing
      effects, and for that reason PSK has not become a standard therapy. The present
      study evaluated the expression of MHC class I in gastric cancer patients who
      received PSK postoperative adjuvant immunochemotherapy, and investigated the
      correlation between MHC class I expression and clinical outcomes. The subjects
      comprised 349 patients with stage II/III gastric cancer, who had received
      adjuvant therapy following curative resection between 1995 and 2008. MHC class I
      expression in the primary lesion was evaluated by immunohistochemical staining.
      Patients were divided into two treatment groups: one was only administered oral
      chemotherapy (chemotherapy-only group) and the other was administered
      chemotherapy plus PSK (PSK group). The clinical outcomes were compared between
      the two groups. The two groups did not differ in regard to their MHC class I
      expression. Expression-negative cases demonstrated 3-year recurrence-free
      survival (RFS) rates of 65% in the PSK group and 47% in the chemotherapy-only
      group. Therefore, the PSK group revealed a prolonged survival. For the 82
      expression-negative cases with pN2 or greater, the RFS rates were 68% in the PSK
      group and 28% in the chemotherapy-only group, representing a significant
      difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC class I
      negative patients, who are in a state of antitumor immunological tolerance, and
      patients with advanced lymph node metastasis of pN2 or greater.

PMID- 22969995
TI  - Membranous and cytoplasmic expression of epidermal growth factor receptor in
      metastatic pancreatic ductal adenocarcinoma.
AB  - Recent studies indicate the clinical significance of the cellular localization of
      epidermal growth factor receptor (EGFR) in a variety of cancer types.
      Internalization of activated EGFR is reported to be closely associated with
      patient prognosis. This study investigated the clinical significance of the
      immunohistochemical localization of EGFR in patients with metastatic pancreatic
      cancers compared to those with surgically resected pancreatic cancers. Using 44
      surgically resected primary pancreatic cancers and 40 primary or meta-static
      tumors from 20 autopsied patients with far advanced pancreatic cancers, the
      incidence of membranous and cytoplasmic EGFR overexpression was compared between
      primary tumors and far advanced tumors by immunohistochemistry using the Dako
      EGFR pharmDxTM kit, a global standard kit for EGFR assay. In the 44 surgically
      resected cancers, 13 (30%) exhibited membranous overexpression of EGFR,
      comprising 1 case (2%) with score 3+ and 12 cases (27%) with score 2+ and 10
      (23%) exhibited cytoplasmic overexpression of EGFR. In the 40 tumors at a far
      advanced stage, the percentage of samples exhibiting positivity for membranous
      and cytoplasmic EGFR overexpression was 48% (19 of 40) comprising 7 (18%) with
      score 2+ and 12 (30%) with score 3+ and 33% (13 of 40), respectively. The far
      advanced tumors tended to show membranous and cytoplasmic EGFR overexpression
      more frequently than the surgically resected tumors, although the difference was
      not significant. These findings suggest that membranous and cytoplasmic
      overexpression of EGFR may be indicative of the potential aggressiveness of
      pancreatic cancers.

PMID- 22969996
TI  - Impact of increased erythropoietin receptor expression and elevated serum
      erythropoietin levels on clinicopathological features and prognosis in renal cell
      carcinoma.
AB  - Erythropoietin (EPO) expression and EPO receptor (EpoR) expression have been
      demonstrated in various malignant tumors. EPO-EpoR signaling can activate several
      downstream signal transduction pathways that enhance tumor aggressiveness. The
      present study was undertaken to evaluate the impact of overexpression of EpoR and
      elevated serum EPO (sEPO) levels on the clinicopathological features and
      prognosis of patients with renal cell carcinoma (RCC). EpoR expression was
      evaluated immunohistochemically in 56 patients. Tumors with a staining intensity
      greater than that of surrounding proximal tubules were defined as tumors with
      high EpoR expression. The association between EpoR expression levels and various
      clinicopathological factors was analyzed. sEPO levels were determined in 138
      patients and its correlation to clinicopathological factors was also analyzed,
      and EpoR expression was determined in surgical specimens removed from 47 of those
      138 patients. Patients with high EpoR expression and patients with sEPO elevation
      had clinicopathological features less favorable than those of other patients.
      Tumors demonstrating high EpoR expression had a significantly higher number of Ki
      67-positive cells compared to those with low EpoR expression. Tumor assemblies in
      microvessels demonstrated high EpoR expression. Patients whose tumors
      demonstrated high EpoR expression and those with sEPO elevation had a
      significantly lower survival rate compared to other patients, and patients with
      both high EpoR expression and sEPO elevation had an extremely poor prognosis.
      Microvascular invasion was an independent factor associated with sEPO elevation,
      suggesting that EPO-EpoR signaling might be important in RCC metastasis. EPO-EpoR
      signaling may be involved in tumor growth and progression in RCC and the
      combination of EpoR expression and sEPO levels may effectively predict clinical
      outcome.

PMID- 22969997
TI  - Metabonomic signature analysis of cervical carcinoma and precancerous lesions in
      women by (1)H NMR spectroscopy.
AB  - (1)H nuclear magnetic resonance (NMR)-based metabonomics has been used to
      characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN)
      and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA)
      and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to
      model the systematic variation related to patients with CIN or CSCC with healthy
      controls. Potential metabolic biomarkers were identified using database
      comparisons, and the one-way analysis of variance (ANOVA) test was used to
      examine the significance of the metabolites. Compared with plasma obtained from
      the healthy controls, plasma from patients with CIN had higher levels of very-low
      density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together
      with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine,
      glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and
      glycoprotein. Plasma from patients with CSCC had higher levels of acetate and
      formate, together with lower levels of creatine, lactate, isoleucine, leucine,
      valine, alanine, glutamine, histidine and tyrosine compared with the plasma of
      the healthy controls. In addition, compared with the plasma of patients with CIN,
      the plasma of CSCC patients had higher levels of acetate, formate, lactate,
      isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine,
      acetylcysteine, myo-inositol, glycoprotein, alpha-glucose and beta-glucose,
      together with lower levels of acetone, unsaturated lipid and carnitine. Moreover,
      the profiles showed high feasibility and specificity by statistical analysis with
      OPLS-DA compared to the Thinprep cytology test (TCT) by setting the
      histopathological outcome as standard. The metabolic profile obtained for
      cervical cancer is significant, even for the precancerous disease. This suggests
      a systemic metabolic response to cancer, which may be used to identify potential
      early diagnostic biomarkers of the cancer and to establish clinical diagnostic
      methods.

PMID- 22969998
TI  - Intratumoral Wnt2B expression affects tumor proliferation and survival in
      malignant pleural mesothelioma patients.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor with a poor
      prognosis. We performed a comprehensive clinical study on the intratumoral
      expression of Wnt1, Wnt2B and Wnt5A in MPM. One hundred and seven MPM patients
      were investigated. Immunohistochemistry was performed to evaluate the
      intratumoral expression of Wnt1, Wnt2B, Wnt5A, survivin and c-Myc, and the Ki-67
      proliferation index. The apoptotic index was evaluated by the TUNEL method. Among
      the 107 MPMs, 23 MPMs (21.5%) were Wnt1-high tumors, 72 MPMs (67.3%) were Wnt2B
      high tumors and 54 MPMs (50.5%) were Wnt5A-high tumors. There was no correlation
      among the levels of Wnt expression. The percentage of Wnt2B-positive tumors was
      significantly higher compared to that of the other Wnts (p<0.0001). Furthermore,
      intratumoral Wnt2B expression significantly correlated with the expression of
      survivin (p<0.001) and c-Myc (p<0.001). Regarding tumor biology, the Ki-67
      proliferation index was significantly higher in the Wnt2B-high tumors than in the
      Wnt2B-low tumors (p=0.0438). In addition, the overall survival was significantly
      lower in patients with Wnt2B-high tumors than in those with Wnt2B-low tumors
      (p=0.0238). A Cox multivariate analysis also demonstrated the Wnt2B status to be
      a significant prognostic factor in MPM patients (p=0.0042). Intratumoral Wnt2B
      expression was associated with the expression of survivin and c-Myc, tumor
      proliferation and patient survival in MPM. Wnt2B is a potential molecular target
      for the treatment of Wnt2B-overexpressing MPMs.

PMID- 22969999
TI  - Genotoxic therapy stimulates error-prone DNA repair in dormant hepatocellular
      cancer stem cells.
AB  - Previous studies have described distinct dormant and proliferating populations of
      cancer stem cells in hepatocellular carcinoma. The CD13 protein is involved in
      the scavenging of reactive oxygen species through the glutathione reductase
      pathway and is associated with resistance to chemotherapy. Whereas CD13(-)
      proliferating cancer stem cells are sensitive to chemotherapy, CD13(+) dormant
      cancer stem cells are associated with the development of resistance to
      chemotherapy. CD13(+) cells in hypoxic areas of the tumour survive chemotherapy,
      leading to subsequent disease relapse and metastasis. Whether CD13(+) dormant
      cells simply resume proliferation following therapy or whether they also acquire
      greater malignant potential, remains unknown. The mechanisms involved also remain
      unclear. In the present study, we investigated the repair of DNA damage in
      CD13(+) dormant and CD13(-) proliferating cells. Total RNA was extracted from
      tissues, and quantitative real-time polymerase chain reaction (PCR) was performed
      for specific genes and GAPDH following PCR. Products were then subjected to a
      temperature gradient of 55-95 degrees C with continuous fluorescence monitoring
      to generate a melting curve. Cells were incubated with primary antibodies, washed
      twice, incubated with fluorescent-labelled secondary antibodies for 30 min on ice
      and analyzed by flow cytometry. The results revealed that the repair of DNA
      damage in CD13(+) dormant cells occurs predominantly through non-homologous end
      joining, a repair process that is error-prone, whereas CD13(-) proliferating
      cells primarily utilise high-fidelity homologous recombination for DNA repair.
      These data indicate that not only is dormancy a protective mechanism for cancer
      stem cells to survive therapy, but it also enhances the generation and
      accumulation of mutations following DNA damage. Therefore, the CD13(+) dormant
      cancer stem cells must be eradicated fully to achieve complete remission of
      cancer.

PMID- 22970000
TI  - Parathyroid hormone-related protein expression, in combination with nodal status,
      predicts bone metastasis and prognosis of breast cancer patients.
AB  - Parathyroid hormone-related protein (PTHrP) has been known to play an important
      role in the formation of meta-static lesions in the bone. However, there remains
      controversy over its practical role in predicting the occurrence of bone
      metastasis and the prognosis of breast cancer patients. In this study, we
      attempted to investigate the clinical value of PTHrP expression status in the
      primary lesions of breast cancer patients. We immunohistochemically investigated
      PTHrP expression in surgically resected specimens from 125 primary breast cancer
      patients whose clinicopathological background and long-term prognosis were
      available. Positive PTHrP staining was demonstrated in 79 (63.2%) tumors. PTHrP
      was expressed significantly more frequently in the tumors of premenopausal
      patients. Bone metastases were significantly more common in patients with T4
      tumors, with a positive node, with distant metastasis and with PTHrP-positive
      tumors. Multivariate logistic analysis revealed positive PTHrP expression as an
      independent risk factor for predicting bone metastasis. PTHrP expression was
      significantly related to a shorter overall survival. Bone metastasis was found
      significantly more frequently (28.3%) in PTHrP- and node-positive cases than in
      double-negative cases, and the rate was more pronounced in postmenopausal cases
      (32.1%). Expression of PTHrP in primary lesions, in combination with positive
      nodal status, is indicative of an increased risk of bone metastasis in breast
      cancer patients.

PMID- 22970001
TI  - Post-training consumption of wheat gluten hydrolysate suppresses the delayed
      onset of muscle injury in soccer players.
AB  - Wheat gluten hydrolysate (WGH) is reported to suppress the muscle injuries
      associated with exercise in long distance running and weight training. In the
      present study, we investigated the effects of WGH consumption on suppression of
      muscle injury after soccer training in a double-blind crossover study.
      Immediately after a mini soccer game, six soccer players consumed 18.0 g of WGH,
      and muscle injury was investigated using serum creatine kinase (CK) as an
      indicator. The results showed a significant increase in serum CK from immediately
      after exercise to 12 h after exercise stress (p<0.05) in the placebo group, while
      serum CK decreased during this same time period in the WGH group, and the
      difference between the two groups was significant. This suggests that WGH
      consumption suppresses delayed-onset muscle injury after exercise in soccer.

PMID- 22970002
TI  - Co-expression of CXCR4 and CD133 proteins is associated with poor prognosis in
      stage II-III colon cancer patients.
AB  - Although CXCR4 and CD133 have been implicated in the metastatic process of
      malignant tumors, the clinicopathological significance of their expression in
      human colon cancer is not fully understood. The present study aimed to examine
      the expression of the CXCR4 and CD133 proteins in cases of stage II or III colon
      cancer and the related lymph nodes and to investigate the clinical and prognostic
      significance of these proteins in colon cancer. Immunohistochemical analysis was
      performed to examine CXCR4 and CD133 protein expression in paraffin-embedded
      stage II or III primary colon cancer tissues and matched lymph nodes. The
      correlation between the expression of the two proteins and clinicopathological
      parameters and the patient 5-year survival was analyzed. CXCR4 expression was
      detected in 74 of the 125 tumors (59.2%) and CD133 expression was detected in 45
      (36.0%). The co-expression of CXCR4 and CD133 (both CXCR4 and CD133 were
      positive) was detected in 29 of the 125 tumors (23.2%). Compared with the other
      combinations, the co-expression of the CXCR4 and CD133 proteins was significantly
      associated with American Joint Committee on Cancer (AJCC) stage (P=0.029) and
      lymph node status (P=0.020). Log-rank analysis revealed that AJCC stage
      (P=0.014), lymph node status (P=0.011), CXCR4 expression (P=0.023), CD133
      expression (P=0.034) and the co-expression of the CXCR4 and CD133 proteins
      (P=0.003) were significant prognostic indicators for the overall survival of
      patients. The results of the present study show that the co-expression of the
      CXCR4 and CD133 proteins is a risk factor for poor overall survival in stage II
      or III colon cancer patients, indicating that the co-expression of the CXCR4 and
      CD133 proteins contributes to the progression of colon cancer.

PMID- 22970004
TI  - Endothelial cell protein C receptor gene 6936A/G polymorphism is associated with
      venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common, yet complex disorder. Genetic factors
      have been suggested to play a role in disease development. We, therefore,
      conducted a case-control study to examine the potential association of the
      6936A/G polymorphism in the endothelial cell protein C receptor (EPCR) gene with
      the occurrence of venous thromboembolism. We measured the plasma levels of
      soluble EPCR (sEPCR) in blood samples collected from 112 patients with VTE and
      112 age- and gender-matched healthy donors using enzyme-linked immunosorbent
      assay (ELISA) and amplified the EPCR gene product by PCR. Gene product bands were
      sequenced to identify EPCR gene polymorphisms. We found that the 6936 AG and GG
      genotypes were over-represented in the VTE patients. By multivariate analysis,
      subjects carrying the 6936 G allele were found to have an increased risk of
      thrombosis (OR=1.784; 95% CI, 1.113-2.891; P<0.05). In conclusion, the EPCR gene
      6936A/G polymorphism, which is associated with elevated plasma sEPCR levels, is a
      potential candidate risk factor for venous thromboembolism.

PMID- 22970003
TI  - Significance of survivin expression: Prognostic value and survival in stage III
      non-small cell lung cancer.
AB  - This study was designed to determine the levels of survivin expression and
      identify its clinical significance as a prognostic factor for stage III non-small
      cell lung cancer (NSCLC). A total of 210 cases of stage III NSCLC were collected
      and the expression levels of survivin and vascular endothelial growth factor A
      (VEGF-A) in tumor tissues were investigated using immunohistochemistry (IHC). The
      medical records of the patients were reviewed to determine the association with
      clinical course. Of the 210 NSCLC tissues, 112 (53.3%) cases demonstrated
      positive expression of survivin protein. Coexpression of survivin and VEGF-A was
      identified. The 5-year survival rate of patients with positive survivin
      expression was significantly lower compared with the survivin-negative cancer
      patients (P<0.05). The expression of survivin in NSCLC correlated with tumor
      size. Survivin and VEGF-A were independent prognostic factors of stage III NSCLC.
      Survivin protein is a valuable marker of prognosis in stage III NSCLC patients.

PMID- 22970005
TI  - Prognostic value of nuclear maspin expression for adjuvant 5-fluorouracil-based
      chemotherapy in advanced gastric cancer.
AB  - To assess the prognostic and predictive value of maspin expression for the
      clinical response to 5-fluorouracil (5-FU)-based chemotherapy in advanced gastric
      cancer (GC) patients, the expression of maspin in primary tumors from 127
      patients with advanced GC was examined using immunohistochemistry. Of the 127
      patients, 74 were treated with surgery alone and 53 received additional adjuvant
      5-FU-based chemotherapy. Nuclear and cytoplasmic maspin expression was observed
      in 46.5 (59/127) and 68.5% (87/127) of patients, respectively. Nuclear maspin
      immunoreactivity was significantly associated with larger tumor size (p=0.036),
      the depth of tumor invasion (p=0.02) and lymph node metastasis (p=0.002).
      Cytoplasmic maspin immunoreactivity was associated with tumor cell
      differentiation but not with the other clinicopathological variables. Nuclear
      maspin immunoreactivity had a significant association with overall survival (OS).
      Among the nuclear maspin-expressing patients, those who were treated with 5-FU
      based adjuvant chemotherapy showed significantly longer OS than those without
      chemotherapy (p=0.0004). In conclusion, nuclear maspin expression is associated
      with adverse clinical outcomes in patients with advanced GC. Patients with
      positive nuclear maspin expression may be more responsive to adjuvant 5-FU
      chemotherapy.

PMID- 22970006
TI  - Feasibility and effect of ultrasound microbubble-mediated wild-type p53 gene
      transfection of HeLa cells.
AB  - Gene therapy holds great promise for the treatment of diseases. The key problem
      of gene therapy is the choice of an effective vector. Ultrasound-mediated
      microbubble technique (UMMT) has already shown promising applications in numerous
      types of tumors apart from cervical carcinoma. In the present study, according to
      the results of an MTT assay, we initially chose an ultrasound intensity of 0.5
      W/cm(2), an ultrasound exposure time of 30 sec and a microbubble concentration of
      10% as the optimum experimental condition for wtp53 plasmid transfection into
      HeLa cells. To further investigate the transfection efficiency of ultrasound
      combined with microbubbles, RT-PCR analysis was used to examine the mRNA level of
      p53. The transfection efficiency in the plasmid plus microbubbles and ultrasound
      group was significantly higher than that of the other groups. Following
      transfection of the wtp53 gene, flow cytometric analysis showed that the cell
      cycle of HeLa cells was arrested in the G1 phase. The results of the present
      study suggest that UMMT, a new gene delivery system, increases the transfection
      efficiency of the wtp53 gene. Moreover, the growth of HeLa cells was arrested by
      introducing wtp53. This study may afford a new trend for the gene therapy of
      cervical carcinoma.

PMID- 22970007
TI  - Screening and identification of serum proteomic biomarkers for gastric
      adenocarcinoma.
AB  - The aim of the present study was to screen for possible serum biomarkers for
      gastric adenocarcinoma. Surface-enhanced laser desorption ionization time of
      flight mass spectrometry (SELDI-TOF-MS) was used to screen serum samples from 109
      cases of gastric adenocarcinoma and 106 control subjects (60 healthy subjects, 30
      patients with chronic superficial gastritis and 16 cases of chronic atrophic
      gastritis). The differentially expressed protein peaks were selected and isolated
      using high performance liquid chromatography (HPLC) and processed with enzyme
      prior to liquid chromatography-mass spectrometry tandem mass spectrometry (LC
      MS/MS) analysis and data mining with software XCalibur program components
      BioWorks 3.2. Among the gastric cancer cases, three differentially expressed
      protein peaks were selected as potential serum biomarkers: the m/z peaks at
      5,906.5 showed increased expression (8.53+/-4.33 in the cancer group, and 0.88+/
      0.31 in the control group); the m/z peaks at 6,635.7 and 8,716.3 showed decreased
      expression (6.54+/-2.44 and 0.93+/-0.29, respectively, in the cancer group and
      17.56+/-4.43 and 2.16+/-0.98, respectively, in the control group) (P<0.01). The
      m/z peaks at 5,906.5, 6,635.7 and 8,716.3, were identified as fibrinogen alpha
      chain, apolipo-protein A-II and apolipoprotein C-I. The combined use of the three
      biomarkers distinguished the cancer group patients from the control group samples
      at a sensitivity of 93.85% (61/65) and a specificity of 94.34% (50/53). In
      conclusion, fibrinogen alpha-chain, apolipoprotein A-II and apolipoprotein C-I
      were identified as potential markers for gastric cancer and appear to have
      diagnostic value for clinical applications.

PMID- 22970008
TI  - Survivin expression in human lung cancer and the influence of its downregulation
      on the biological behavior of human lung cancer cells.
AB  - The aim of the present study was to detect the expression of survivin in human
      lung cancer and to investigate the influence of its downregulation on the
      biological behavior of A549 lung cancer cells. The high expression of survivin in
      human lung cancer was verified by immunohistochemistry. Survivin small
      interfering RNA (siRNA) and unrelated sequence were synthesized and the siRNA
      lentiviral vector was constructed. The vector was transfected into A549 lung
      cancer cells, in which the clone with stable expression was screened out. We
      blocked the expression of survivin mRNA and protein by RNA interference (RNAi)
      technique. The downregulation of survivin mRNA and protein expression was
      confirmed by real-time quantitative PCR and western blotting. The proliferative
      activity and growth rate of A549 cells were determined by colony formation assay
      and mononuclear cell direct cytotoxicity assay (MTT assay). The reconstituted
      basement membrane (RBM) penetrating capacity was determined by cell invasion
      assay. The cell movement and migratory capacity were detected by wound-healing
      repair assay. The results showed that the sequence-specific siRNA significantly
      downregulated the expression of survivin at both the mRNA and protein levels.
      Downregulation of survivin expression dramatically decreased the invasive and
      metastatic capacities of the cells, suppressed the proliferation, decelerated the
      rate of growth, reduced the number of clones on soft agar and decreased the
      capacity of RBM penetration and migration. In conclusion, survivin, which plays
      an important role in carcinogenesis and development of lung cancer, can be
      effectively downregulated using the RNAi technique.

PMID- 22970009
TI  - Hyalinizing trabecular tumor of the thyroid: Case report and review of the
      literature.
AB  - In 1987, Carney et al described a rare thyroid tumor termed hyalinizing
      trabecular adenoma presenting characteristics consisting of a trabecular growth
      pattern and hyalinizing stroma. In subsequent reports, the observed nuclear
      features and RET alterations led this tumor to be linked to papillary carcinoma.
      Subsequent reports concerning hyalinizing trabecular carcinoma further
      complicated its classification. To avoid uncertainties, the definition of
      hyalinizing trabecular tumor (HTT) is more widely used. Herein, a case of HTT is
      reported in detail, and the circumstances are also discussed. HTT is thought to
      be particularly differentiated from papillary carcinoma despite the identical
      high frequency of nuclear grooves and cytoplasmic inclusions, and MIB-1-positive
      staining is one of the most accurate diagnostic methods due to the distinct
      membrane-positive pattern noted in HTT. It is believed that most HTTs are benign
      and lobectomy is the standard treatment. Pathologists should offer surgeons
      information concerning diagnosis overlapping with effective treatment.

PMID- 22970010
TI  - Continuous administration of recombinant human endostatin (Endostar): A pre
      clinical safety study.
AB  - The aim of this study was to evaluate the safety of the continuous administration
      of recombinant human endostatin (Endostar) in healthy mice. A total of 16 nude
      mice were randomly divided into four treatment groups: a continuous
      administration group injected intraperitoneally (i.p.) with 14 mg/kg Endostar
      over seven days, an intermittent administration group injected i.p. with 2 mg/kg
      Endostar daily for seven days, a saline injection group and an untreated control
      group. All mice were implanted with an intraperitoneal mini-osmotic drug pump
      filled with Endostar or saline. The serum concentration of Endostar, the cell
      fraction of CD11b(-)CD146(+)CD105(+) vascular endothelial cells in the peripheral
      blood, the injury of the myocardial, lung and kidney tissues and the density of
      microvessels within these organs were observed 24 h after the termination of drug
      or saline administration. Only trace amounts of Endostar were detected in the
      serum of the continuous administration and intermittent administration groups.
      Myocardial, lung and kidney tissues exhibited no detectable signs of injury and
      no differences in the density of microvessels were found in these organs among
      the four groups. Yet, the cell fraction (in %) of CD11b(-)CD146(+)CD105(+)
      vascular endothelial cells in the peripheral blood was higher in the continuous
      administration group compared with that in the other treatment groups (P=0.011).
      This suggests that intermittent Endostar delivery did not significantly impact
      the vascular endothelium, while continuous Endostar administration may promote
      injury of the endothelium. In conclusion, the continuous administration of
      Endostar does not appear to be a safe method by which to administer this
      antiangiogenic agent to healthy nude mice.

PMID- 22970011
TI  - Syphilis manifesting as a nasopharyngeal carcinoma with cervical lymphadenopathy:
      A case report.
AB  - The present case report describes a case of syphilitic lymphadenopathy and raises
      the awareness of the differential diagnosis of cervical lymphadenopathy. A 50
      year-old male worker presented with a 6-month history of enlarged and growing
      lymph nodes in the right upper neck and a blood-tinged post-nasal drip. Physical
      examination showed multiple enlarged lymph nodes located in the right upper neck.
      On nasopharyngoscopy, a mass was found in the nasopharynx. The histopathology of
      both the nasopharyngeal mass and the enlarged lymph nodes revealed non-specific
      inflammation. Rapid plasma reagin test results (titer, 1:1280) and Treponema
      pallidum particle assay results (titer, 1:2560) were positive. Subsequently, a
      diagnosis of syphilis was confirmed clinically and serologically. The reaction
      after penicillin treatment further confirmed the syphilis diagnosis. Thus,
      syphilis should be considered as a possibility in the differential diagnosis of
      cervical lymphadenopathy.

PMID- 22970012
TI  - Expression of p14(ARF), p15(INK4b), p16(INK4a) and skp2 increases during
      esophageal squamous cell cancer progression.
AB  - Esophageal carcinoma is the sixth most common cause of cancer-related mortality
      in the world. Senescence and apoptosis are assumed to be two main mechanisms that
      inhibit age-related carcinogenesis. p14(ARF), p15(INK4b) and p16(INK4a), which
      are known to induce senescence by regulating G(1) cell cycle arrest, have been
      identified as senescence markers. However, the mechanism by which senescence and
      apoptosis causes neoplasia in esophageal squamous cell carcinoma (ESCC) has not
      been identified. In this study, 20 cases of normal esophageal tissues, 11 cases
      of esophageal intraepithelial dysplasia (EID) and 60 cases of ESCC were obtained
      and pathologically diagnosed. Immunohistochemical staining was performed to
      assess the expression of p14(ARF), p15(INK4b), p16(INK4a), skp2, bcl-2 and ki-67.
      The senescence markers p14(ARF) and p16(INK4a) were found to be expressed in 15
      and 10% of the normal tissues, 82 and 73% of the EID cases and 100 and 88% of the
      ESCC cases, respectively. The expression of p15(INK4b) was low in normal tissues,
      while 92% of the ESCC specimens were diffusely and markedly stained, involving
      the basal, middle and upper portion of the epithelium. The nuclear expression
      markers ki-67 and skp2 were highly expressed in ESCC tissues (100 and 72%,
      respectively). bcl-2 was expressed weakly in normal tissues (10%) and
      demonstrated various staining patterns in carcinoma specimens (strong in 60%,
      negative in 40%). MI was 0.09% in normal tissues and 0.95% in the ESCC specimens.
      Apart from the increased proliferation in esophageal carcinogenesis, as indicated
      in the ki-67 and skp2 indices, there was an increased expression of senescence
      associated molecular markers in the ESCC specimens, which indicates that the
      senescence pathway may be activated and become a part of cancer development. Of
      greatest interest to us was that, when compared with clinical information, the
      expression of the senescence markers was markedly high in the poorly
      differentiated specimens with lymph node metastasis, indicating that senescence
      markers may have diagnostic potential in clinical settings.

PMID- 22970013
TI  - TAT-Apoptin induces apoptosis in the human bladder cancer EJ cell line and
      regulates Bax, Bcl-2, caspase-3 and survivin expression.
AB  - In order to identify the antitumor effect of TAT-Apoptin on the human bladder
      cancer EJ cell line and study its impact on the expression of the apoptosis
      related genes bax, bcl-2, caspase-3 and survivin, the MTT assay, real-time
      quantitative PCR and western blot analysis were used in this study. The results
      of the MTT assay indicated that TAT-Apoptin was able to inhibit the proliferation
      of EJ cells in a dose-dependent manner. The expression of Bax, Bcl-2, Caspase-3
      and Survivin mRNA and protein following the treatment of the EJ cells with TAT
      Apoptin (0.1, 0.5, 1, 10, 50 and 100 MUg/ml) for 24, 48 and 72 h was analyzed.
      Cell proliferation was significantly different after treatment with the various
      concentrations of TAT-Apoptin and the durations of treatment. The level of
      expression of Bcl-2 and Survivin in EJ cells decreased significantly, while that
      of Bax and Caspase-3 increased significantly at the mRNA and protein levels.

PMID- 22970014
TI  - microRNA expression pattern and its alteration following celecoxib intervention
      in human colorectal cancer.
AB  - Accumulating evidence suggests that aberrant expression of microRNAs (miRNAs) is
      involved in several diseases, including cancer. This study aimed to investigate
      the miRNA expression pattern and its alteration following celecoxib intervention
      for human colorectal cancer (CRC). The miRNA expression profiles of CRC tissues,
      matched adjacent normal colorectal mucosae and HT-29 cells treated with celecoxib
      were determined using miRNA microarray, and further confirmed using the
      quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). The
      target genes of the aberrant miRNAs in HT-29 cells treated with celecoxib were
      further assessed through bioinformatic analysis. Results from this study
      demonstrated a significant increase in the expression of 35 miRNAs and a decrease
      in 30 miRNAs in the carcinoma tissues compared to the normal tissues (P<0.001).
      Of the 28 aberrantly expressed miRNAs, 20 were upregulated and 8 were
      downregulated in the HT-29 cells treated with celecoxib compared to the matched
      control cells (P<0.01). Furthermore, miR-552 was found to be correlated with
      clinical stage, lymph node and distant metastases (P<0.05). Stage and distant
      metastases revealed differential expression of miR-139-3p and grade disclosed
      aberrant expression of miR-142-3p. In addition, multiple target genes involved in
      several essential survival pathways were found be modulated by the aberrantly
      expressed miRNAs in HT-29 cells treated with celecoxib. Our data revealed that a
      common pattern of miRNA expression in the colorectum could distinguish malignant
      tissue from normal mucosa. Celecoxib inhibited HT-29 cell growth in vitro which
      was partly attributable to the altered expression of miRNAs. miRNAs may be
      involved in CRC tumorigenesis and can serve as potential therapeutic targets.

PMID- 22970015
TI  - Synergistic impact of Lactobacillus fermentum, Lactobacillus plantarum and
      vincristine on 1,2-dimethylhydrazine-induced colorectal carcinogenesis in mice.
AB  - Lactobacillus sp. is the most dominant probiotic strain of bacteria. Evidence
      indicates that the consumption of Lactobacillus sp. reduces the risk of
      colorectal cancer in animal models. The present study was carried out to
      determine whether administration of Lactobacillus fermentum/ Lactobacillus
      plantarum alone or in combination with vincristine have a synergistic impact on
      the control of colorectal cancer in an animal model. Mice with 1,2
      dimethylhydrazine (DMH) hydrochloride-induced colon cancer were fed with L.
      fermentum and L. plantarum isolated along with vincristine. An increase in body
      weight, a decrease in ammonia concentration, a decrease in beta glucosidase and
      beta glucuronidase enzyme activity and a reduction in the number of crypts in the
      mice in the pre-carcinogen-induced group was noted when compared to these
      variables in the post-carcinogen-induced group. The body weight of the mice fed
      L. fermentum along with vincristine was increased (6.5 g), and was found to be
      3.5 times higher compared to that of the control. A marked decrease in the
      ammonia concentration (240 mg), and beta glucosidase (0.0023 IU) and beta
      glucopyranose enzyme activity (0.0027 IU) was observed; 22.59% less ammonia
      concentration, 73.26% less beta glucosidase activity and 56.46% less beta
      glucuronidase enzyme activity was noted when compared to the control. A
      significant reduction in the number of aberrant crypt foci (ACF) (90%) was
      observed when compared to the control. Maximum protection was observed in the
      mice fed the probiotics and vincristine prior to cancer induction. Among the
      different dietary combinations tested in the present study, L. fermentum and
      vincristine showed a more extensive reduction in ammonia concentration, beta
      glucosidase, beta glucuronidase activity and the number of ACF.

PMID- 22970016
TI  - Comparative serum proteomic analysis involving liver organ-specific metastasis
      associated proteins of nasopharyngeal carcinoma.
AB  - Metastasis is the main cause of cancer-related mortality; patients with liver
      metastases (LM) have the worst prognosis among patients with nasopharyngeal
      carcinoma (NPC). However, at present, few biomarkers for detecting organ-specific
      metastasis have been identified. Proteomics, an ultra-sensitive analytical
      technique, can detect molecular changes before organ-specific metastasis occurs.
      Analysis with matrix-assisted, laser desorption-ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS), combined with magnetic chemical affinity beads is a
      new technique for evaluating protein separation. We sought to identify potential
      liver-specific, metastasis-associated proteomic printing in patients with NPC. We
      examined 64 serum samples from 50 patients who had pathologically confirmed NPC
      and 14 who had pathologically confirmed non-NPC with LM using MALDI-TOF-MS with
      weak cation bead protein chips. During follow-up of at least 37 months (maximum,
      176 months) following radiotherapy, we confirmed 16 cases of LM (LM NPC), 16
      cases without LM (non-LM NPC) and 18 cases without metastasis (non-M NPC). Using
      comparison analysis, 4 protein mass peaks, 4155.34, 4194.87, 4210.78 and 4249.56
      m/z were identified as liver-specific, metastasis-associated protein peaks in NPC
      and two of them (4155 and 4249 m/z) met two different statistical criteria in
      both ClinProt software analyses and discriminant analyses. Models based on the 4
      potential serum markers of NPC discriminated between LM NPC, non-LM NPC, non-M
      NPC and non-NPC LM analyzed with sieved markers. The recognition capability and
      cross-validation of these models for differentiating the above 4 groups are all
      approximately 80%. MALDI-TOF-MS combined with tree analysis models may provide a
      clinical diagnostic platform for detecting potential liver-specific, metastasis
      associated proteomic printing in NPC. However, markedly differential proteins
      still need to be identified.

PMID- 22970017
TI  - Effect of healthcare insurance policy on the quality of life of chronic hepatitis
      C patients receiving interferon alpha-2a plus ribavirin therapy.
AB  - The aim of this study was to evaluate the effect of pegylated interferon alpha-2a
      plus ribavirin therapy on the quality of life (QOL) of chronic hepatitis C
      patients when this treatment was paid for by healthcare insurance. The QOL
      questionnaire (GQOLI-74) was used to assess patient QOL. A total of 42 cases
      received 1-year pegylated interferon alpha-2a plus ribavirin treatment paid for
      by Guangzhou Medical Insurance (group A), and 30 cases received treatment self
      subsidized by the patients themselves (group B). Another 30 patients did not
      receive interferon therapy (group C). All groups completed the evaluation twice;
      prior to interferon treatment (T0) and at the end of treatment (T1). There was no
      statistically significant difference among the three groups (P>0.05). At T1,
      patients in group A had higher scores for each questionnaire dimension and a
      higher total score than those of group C (P<0.05). Patients in group B also had
      higher scores than those of group C (P<0.05), except for material well-being
      (P=0.305). Compared with group B, patients in group A had higher scores for
      mental function, material well-being and a higher total score (P<0.05). Patients
      in group A had higher scores for each dimension and a higher total score at T1
      than at T0 (P=0.05), while patients in group B had higher scores for physical
      function, social function and a higher total score at T1 than at T0 (P=0.05).
      Pegylated interferon alpha-2a plus ribavirin treatment is able to improve the QOL
      of chronic hepatitis C patients. Patients whose treatment was financed by medical
      insurance exhibited increased improvement in QOL compared to those who paid for
      their own treatment.

PMID- 22970018
TI  - Methylation of the RASSF1A and RARbeta genes as a candidate biomarker for lung
      cancer.
AB  - Promoter methylation of the RASSF1A and RARbeta genes has been associated with
      susceptibility to different types of cancer. In addition, RASSF1A and RARbeta
      methylation plays an important role in the pathogenesis of lung cancer. We
      investigated the aberrant promoter methylation of RASSF1A and RARbeta in lung
      cancer patients using methylation-specific polymerase chain reaction (MSP).
      Aberrant promoter methylation of the RASSF1A gene was detected in 45 of 56
      (80.36%) cancer patients and aberrant promoter methylation of the RARbeta gene
      was found in 48 of 56 (85.71%) cases; promoter methylation of both genes was
      found in 42 of 56 (75%) lung cancer cases. None of the 52 samples from controls
      exhibited DNA methylation in these two target genes. Methylation was
      significantly associated with the lung cancer cases compared to controls for the
      RASSF1A gene (adjusted OR=7.50; 95% CI, 3.935-14.296; p<0.001); similar results
      were obtained for methylation of the RARbeta gene (adjusted OR=5.727; 95% CI,
      3.348-9.797; p<0.001). In addition, the association remained significant in these
      two target genes (adjusted OR=8.429; 95% CI, 4.205-16.896; p<0.001). Our results
      indicated that the high percentage of promoter methylation in the RARbeta and
      RASSF1A genes indicate their important role in the development of lung cancer in
      the population studied, and that risk of lung cancer for carriers positive for
      both genes is higher than in single-gene positive carriers, which may serve as a
      useful marker for prognosis and a target for the treatment of lung cancer.

PMID- 22970019
TI  - Diagnostic accuracy of vascular endothelial growth factor for malignant pleural
      effusion: A meta-analysis.
AB  - Since the diagnostic accuracy of conventional examinations for malignant pleural
      effusion (MPE) is limited, a number of studies have investigated the utility of
      pleural vascular endothelial growth factor (VEGF) in the diagnosis of MPE. The
      present meta-analysis aimed to determine the overall accuracy of a VEGF test in
      the diagnosis of MPE. A systematic review of studies published in English was
      conducted and the data concerning the accuracy of pleural VEGF assays in the
      diagnosis of MPE were pooled with random effects models. The overall test
      performance was summarized using receiver operating characteristic curves. Ten
      studies, based on 1,025 patients, met the inclusion criteria for the meta
      analysis and the summary estimates for VEGF in the diagnosis of MPE were:
      sensitivity 0.75 [95% confidence interval (CI), 0.72-0.79], specificity 0.72 (95%
      CI, 0.68-0.76), positive likelihood ratio 2.94 (95% CI, 1.97-4.41), negative
      likelihood ratio 0.38 (95% CI, 0.27-0.51) and diagnostic odds ratio 9.05 (95% CI,
      4.60-17.80). The summary receiver operating characteristic curve indicated that
      the maximum joint sensitivity and specificity was 0.75; the area under the curve
      was 0.82. Our findings suggest that the determination of pleural VEGF may improve
      the accuracy of MPE diagnosis, while the results of VEGF assays should be
      interpreted in parallel with conventional test results and other clinical
      findings.

PMID- 22970020
TI  - Downregulation of phosphatase of regenerating liver-3 is involved in the
      inhibition of proliferation and apoptosis induced by emodin in the SGC-7901 human
      gastric carcinoma cell line.
AB  - Emodin, an anthraquinone derivative isolated mainly from the root and rhizome of
      the medicinal plant Rheum palmatum L., was found to exert anticancer effects on
      various cultured cancer cells. Phosphatase of regenerating liver-3 (PRL-3), a
      novel gene, has been known to play an important role in the promotion of cellular
      proliferation as well as inhibition of apoptosis in cancer cells. However, there
      is relatively little information in the published literature with regard to the
      anticancer mechanism of emodin, and whether emodin is involved in the regulation
      of PRL-3 in human gastric carcinoma cells is not known. In the present study, we
      investigated the effects of emodin on SGC-7901 cell proliferation, apoptosis and
      regulation of PRL-3. The results showed that the proliferation of SGC-7901 cells
      was inhibited by emodin in a time- and concentration-dependent manner. The
      results also showed that early apoptosis rates increased in a concentration
      dependent manner after emodin treatment. Furthermore, real-time quantitative PCR
      analysis showed that PRL-3 mRNA was significantly decreased by treatment with
      emodin. Western blotting showed that PRL-3 protein expression was also
      downregulated significantly. Overall, the present study demonstrated that emodin
      inhibited cell growth and induced apoptotic cell death in the SGC-7901 human
      gastric carcinoma cell line. Downregulation of PRL-3 is involved in the
      inhibition of proliferation and apoptosis induced by emodin. PRL-3 may be a new
      potential therapeutic target for gastric cancer using emodin.

PMID- 22970021
TI  - The TNF-alpha-308G/A polymorphism is associated with migraine risk: A meta
      analysis.
AB  - Migraine is a neurasthenia and the genetic etiology has not been determined.
      Several studies concerning the correlation between the tumor necrosis factor
      (TNF)-alpha-308G/A polymorphism and migraine have been published, but their
      results remain controversial and the small samples in each study do not allow
      sufficient statistical power. In the present study, odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of the association
      between the polymorphism and migraine. An inverse-variance method was applied to
      estimate the frequency of the putative risk allele in the controls. Heterogeneity
      was determined using Cochran's Q test and the inconsistency index (I(2)). Begg's
      test and the inverted funnel plot were used to assess the publication bias. Five
      studies on Asian populations, comprising 985 cases and 958 controls, were
      included in the meta-analysis. The overall results revealed that the TNF-alpha
      308G/A polymorphism was associated with migraine risk in Asians. The ORs were
      1.735 (95% CI, 1.129-2.666) for A vs. G; 1.781 (95% CI, 1.166-2.718) for GA vs.
      GG; 1.821 (95% CI, 1.153-2.874) for AA+GA vs. GG. The subgroup analysis was based
      on migraine with aura (MA) and migraine without aura (MO) and there was a
      statistically significant result for MA [the OR was 1.728 (95% CI, 1.095-2.726)
      for GA vs. GG and 1.651 (95% CI, 1.049-2.598) for AA+GA vs. GG] but not for MO.
      In conclusion, the TNF-alpha -308G/A polymorphism was associated with migraine
      risk.

PMID- 22970022
TI  - Expression and subcellular localization of menin in human cancer cells.
AB  - The aim of this study was to elucidate the expression and localization of menin,
      a protein encoded by the multiple endocrine neoplasia type I (MEN1) gene, in 13
      human cancer cell lines. Reverse transcription-polymerase chain reaction (RT-PCR)
      was used to determine the expression of the menin gene. The localization of the
      menin protein was detected by immunofluorescence microscopy. Western blotting was
      used to determine the quantity of menin in the nucleus, cytosol and membrane of
      the cells. RT-PCR revealed that menin was expressed in all the cell lines
      examined in this study. Immunofluorescence microscopy revealed that menin was
      located primarily in the nucleus. In the GES-1 (transformed human gastric
      epithelium), MCF-7 (breast cancer), SGH44 (brain glioma) and HeLa (cervical
      cancer) cell lines, menin was also found to be localized to the membrane, cytosol
      and nucleus. Moreover, in SGH44 cells more menin was located in the cytosol than
      the nucleus. Similar findings were obtained by western blotting. In the GES-1 and
      MKN-28 cells undergoing octreotide treatment, cytoplasmic menin was significantly
      increased compared with the control groups. Therefore, we suggest that menin is
      expressed in a number of human cancer cell lines and that the cytosolic
      distribution increases when the cells undergo octreotide treatment, indicating a
      new role for menin.

PMID- 22970023
TI  - Autoantibodies against the signal peptide domain of MUC1 in patients with
      multiple myeloma: Implications for disease diagnosis and prognosis.
AB  - Naturally generated autoantibodies to tumor-associated antigens such as MUC1 can
      assist in cancer diagnosis and prognosis. While previous studies have
      concentrated on the tandem repeat array domain of MUC1, here we focused on MUC1's
      signal peptide domain. We used ELISA assays with MUC1-specific epitopes and
      antibodies to quantify soluble MUC1 antigen and anti-MUC1 autoantibodies against
      the tandem repeat array and signal peptide domains in 15 naive donors and 27
      multiple myeloma cancer patients. We showed a significant increase in up to 24
      fold (P<0.004) only in the levels of anti-MUC1 signal peptide autoantibodies in
      the sera of multiple myeloma patients vs. naive donors. This increase stemmed
      chiefly from the preferred immunogenicity of the signal peptide. Moreover, a
      significant positive correlation (R(2)=0.5361, P<0.048, Pearson correlation) was
      shown between the levels of soluble MUC1 and anti-MUC1 signal peptide
      autoantibodies in multiple myeloma patients with progressive disease while under
      therapy. This is an initial report on the existence of autoantibodies to a signal
      peptide domain in general and to the MUC1 signal peptide domain in particular in
      cancer patients. The autoantibodies had MUC1 rather than signal peptide
      specificity. The specific nature of the antigen leading to generation of these
      autoantibodies is still unclear because it is unlikely that the target antigen is
      a major histo-compatibility complex-peptide complex and we could not trace
      soluble MUC1 signal peptide fragments in naive donors and multiple myeloma
      patients. Further validation of these findings may improve diagnostic and
      prognostic capabilities for MUC1-positive multiple myeloma patients and
      potentially, patients with other MUC1-positive cancers, as well.

PMID- 22970024
TI  - Strategies to optimize radiotherapy based on biological responses of tumor and
      normal tissue.
AB  - Rapid developments in radiation oncology are currently taking place. Radiation
      induced responses are being increasingly used for radiotherapy modification based
      on advancements in radiobiology. In the process of radiation treatment,
      radiobiological responses of tumor and normal tissue in patients are monitored
      non-invasively by a variety of techniques including imaging, biological methods
      and biochemical assays. Information collected using these methods and data on
      responses are further incorporated into radiotherapy optimization approaches,
      which not only include the optimization of radiation treatment planning, such as
      dose distributions in targets and treatment delivery, but also include radiation
      sensitivity modification and gene radiotherapy of the tumor and normal tissue.
      Hence, the highest tumor control rate is obtained with the utmost protection
      being afforded to normal tissue under this treatment modality.

PMID- 22970026
TI  - Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells.
AB  - Phosphodiesterases (PDEs) are important regulators of signal transduction
      processes. Eleven PDE gene families (PDE1-11) have been identified and several
      PDE isoforms are selectively expressed in various cell types. PDE4 family members
      specifically hydrolyze cyclic AMP (cAMP). Four genes (PDE4A-D) are known to
      encode PDE4 enzymes, with additional diversity generated by the use of
      alternative mRNA splicing and the use of different promoters. While PDE4
      selective inhibitors show therapeutic potential for treating major diseases such
      as asthma and chronic obstructive pulmonary disease, little is known concerning
      the role of PDE4 in malignant melanoma. In this study, we examined the role of
      PDE4 in mouse B16-F10 melanoma cells. In these cells, PDE4 activity was found to
      be ~60% of total PDE activity. RT-PCR detected only PDE4B and PDE4D mRNA. Cell
      growth was inhibited by the cAMP analog, 8-bromo-cAMP, but not by the specific
      PDE4 inhibitors, rolipram and denbufylline, which increased intracellular cAMP
      concentrations. Finally, migration of the B16-F10 cells was inhibited by the PDE4
      inhibitors and 8-bromo-cAMP, while migration was increased by a protein kinase A
      (PKA) inhibitor, PKI(14-22), and was not affected by 8-pCPT-2'-O-Me-cAMP, which
      is an analog of exchange protein activated by cAMP (Epac). The inhibitory effect
      of rolipram on migration was reversed by PKI(14-22). Based on these results, PDE4
      appears to play an important role in the migration of B16-F10 cells, and
      therefore may be a novel target for the treatment of malignant melanoma.

PMID- 22970025
TI  - microRNA signature for human pancreatic cancer invasion and metastasis.
AB  - Pancreatic cancer has the poorest prognosis among all human malignant solid
      tumors, mainly due to its high invasive and metastatic biological features.
      microRNAs (miRNAs) are a group of endogenous and small non-coding RNA molecules
      18-25 nucleotides in length, functioning as either tumor-suppressor genes or
      oncogenes. Evidence has shown that regulation of miRNAs in pancreatic cancer is
      associated with tumor growth, invasion, metastasis and resistance to therapy.
      Over the last decade, many studies have also found that there is a close
      relationship between miRNAs and biological characteristics of pancreatic cancer
      invasion and metastasis, such as the presence of cancer stem cells, epithelial
      mesenchymal transition (EMT) phenotype, DNA methylation or epigenetic alteration,
      and the activation of some specific signaling pathways. Therefore, better
      understanding of the complex role of miRNAs in the development and progression of
      pancreatic cancer metastasis may provide new insights that could be of
      therapeutic consequence. In this brief review, we discuss the literature
      concerning the correlation between miRNAs and pancreatic cancer, focusing on
      miRNAs that contribute to pancreatic cancer invasion and metastasis, particularly
      on cancer stem cell characteristics, the EMT process, epigenetic modifications
      and tumor-associated signaling pathways.

PMID- 22970027
TI  - Safety and effectiveness of mechanical versus hand suturing of intestinal
      anastomoses in an animal model of peritonitis.
AB  - Mechanical stapling for colorectal anastomosis is popular, but the safety of its
      use for anastomosis in peritonitis is unclear. We evaluated the safety and
      effectiveness of mechanically stapled vs. hand-sutured anastomosis by comparing
      wound healing in an animal model of bacterial peritonitis. Male Sprague-Dawley
      (n=48) rats underwent cecal ligation and puncture. After 24 h, rats were divided
      into two groups: the stapler group (cecal resection with mechanical stapler,
      n=24) and the hand-sutured group (cecal resection and stump closure with surgical
      absorbable suture, n=24). Anastomotic segments were excised and as indicators of
      wound healing, anastomotic bursting pressure (ABP) and tissue hydroxyproline
      concentration were determined over time. After harvesting, anastomotic segments
      were analyzed by quantitative real-time polymerase chain reaction (PCR) to
      determine relative expression of transforming growth factor-beta(1) (TGF-beta(1))
      and vascular endothelial growth factor (VEGF) normalized to that of a
      constitutive gene. The operative time was significantly shorter in the stapler
      vs. the hand-sutured group. Both groups showed progressive increases in ABP over
      the postoperative period. ABP was significantly higher in the stapler vs. the
      hand-sutured group on postoperative days (PODs) 0 and 3. Tissue hydroxyproline
      concentration increased from POD 7 in both groups, but between-group difference
      was not significant. Both groups showed progressive increases in TGF-beta(1) and
      VEGF expression during the 7-day postoperative period. On POD 5, TGF-beta(1) gene
      expression was higher in the stapler vs. the hand-sutured group. VEGF gene
      expression was identical in both groups. In conclusion, anastomosis by stapler is
      safer and more effective than that by hand suturing in bacterial peritonitis,
      since it requires less operating time and creates stronger anastomoses in the
      early postoperative period.

PMID- 22970028
TI  - Radiation dose to the brachial plexus in nasopharyngeal carcinoma treated with
      intensity-modulated radiation therapy: An increased risk of an excessive dose to
      the brachial plexus adjacent to gross nodal disease.
AB  - This retrospective study aimed to evaluate the dose to the brachial plexus in
      patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated
      radiation therapy (IMRT). Twenty-eight patients were selected and the brachial
      plexus was delineated retrospectively. Brachial plexus adjacent/not adjacent to
      nodes were defined and abbreviated as BPAN and BPNAN, respectively. Dose
      distribution was recalculated and a dose-volume histogram was generated based on
      the original treatment plan. The maximum dose to the left brachial plexus was
      59.12-78.47 Gy, and the percentage of patients receiving the maximum dose
      exceeding 60, 66 and 70 Gy was 96.4, 57.1 and 25.0%, respectively; the maximum
      dose to the right brachial plexus was 59.74-80.31 Gy, and the percentage of
      patients exposed to a maximum dose exceeding 60, 66 and 70 Gy was 96.4, 64.3 and
      39.3%, respectively. For the left brachial plexus, the maximum doses to the BPANs
      and the BPNANs were 72.84+/-3.91 and 64.81+/-3.47 Gy, respectively (p<0.001). For
      the right brachial plexus, the maximum doses to the BPANs and the BPNANs were
      72.91+/-4.74 and 64.91+/-3.52 Gy, respectively (p<0.001). The difference between
      the left BPANs and the left BPNANs was statistically significant not only for V60
      (3.60 vs. 1.01 cm(3), p=0.028) but also for V66 (1.26 vs. 0.11 cm(3), p=0.046).
      There were significant differences in V60 (3.68 vs. 1.16 cm(3), p<0.001) and V66
      (1.83 vs. 1.23 cm(3), p=0.012) between the right BPANs and the right BPNANs. In
      conclusion, a large proportion of patients were exposed to the maximum dose to
      the brachial plexus exceeding the Radiation Therapy Oncology Group-recommended
      restraints when the brachial plexus was not outlined. The BPANs are at a
      significantly higher risk of receiving an excessive radiation dose when compared
      to the BPNANs. A further study is underway to test whether brachial plexus
      contouring assists in the dose reduction to the brachial plexus for IMRT
      optimization.

PMID- 22970029
TI  - Declines in serum CYFRA21-1 and carcinoembryonic antigen as predictors of
      chemotherapy response and survival in patients with advanced non-small cell lung
      cancer.
AB  - The aim of this study was to investigate the clinical value of serum cytokeratin
      19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in the prediction of
      chemotherapy response and prognosis in patients with advanced non-small cell lung
      cancer (NSCLC). Serum CYFRA21-1 and CEA levels of 98 patients with advanced NSCLC
      were measured using immunoradiometric kits prior to and after 2 cycles of
      chemotherapy. After 2 cycles of chemotherapy, 45 patients achieved a radiological
      objective response (OR), 30 patients achieved stable disease (SD) and 23 patients
      had progressive disease (PD). Serum CYFRA21-1 and CEA were significantly
      decreased compared to baseline levels (P<0.001). By ROC curve analysis, a >=60%
      reduction in CYFRA21-1 and a >=25% reduction in CEA were the optimal cut-off
      levels with best sensitivity and specificity for the diagnosis of radiologic OR.
      The median survival of all patients was 10.2 months (range 2.6-26.3). Univariate
      survival analysis showed that the Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) score, radiologic OR, a >=60% reduction in CYFRA21-1 and
      a >=25% reduction in CEA were significant prognostic factors for better overall
      survival. The median overall survival time in patients with a >=60% reduction in
      CYFRA21-1 was significantly longer than in those with a <60% reduction (P<0.001).
      Similarly, the median overall survival time in patients with a >=25% reduction in
      CEA was also significantly longer than in those with a <25% reduction (P<0.001).
      Multivariate analysis showed that ECOG PS score, a >=60% reduction in CYFRA21-1
      and a >=25% reduction in CEA were independent prognostic factors of survival,
      while radiologic OR was not. In conclusion, a >=60% reduction in CYFRA21-1 and a
      >=25% reduction in CEA may be reliable surrogate markers for the prediction of
      chemothrapy response and prognosis, especially for the diagnosis of radiologic
      OR.

PMID- 22970030
TI  - Efficacy and tolerability of oxycodone in moderate-severe cancer-related pain: A
      meta-analysis of randomized controlled trials.
AB  - In order to evaluate the efficacy and tolerability of oxycodone in moderate
      severe cancer-related pain, we conducted a systematic review of randomized
      controlled trials (RCTs). Publications addressing the efficacy and tolerability
      of oxycodone in moderate-severe cancer-related pain were selected from the
      Cochrane library, PubMed, Embase and CBM databases. Data were extracted from the
      studies by two independent reviewers. The meta-analysis was performed by RevMan
      5.0.25 and STATA 9.2 software. From these data, odds ratios (ORs) or the standard
      mean difference (SMD) with 95% confidence intervals (CIs) were calculated.
      Finally, only seven RCTs were retrieved with a total of 613 cancer patients with
      moderate-severe pain. The meta-analysis results showed that oxycodone was
      statistically superior to other strong opioids based on pain intensity scores
      following intervention [weighted mean difference (WMD), 0.25; 95% CI, 0.05-0.45;
      P=0.01; WMD, -1.30; 95% CI, -1.55-1.05; P<0.001, respectively]. In addition,
      there were statistically significant differences between oxycodone and other
      strong opioids in cancer-related pain on the obvious effective rate and the
      overall effective rate (OR, 2.03; 95% CI, 1.40-2.95; P=0.0002; OR, 1.94; 95% CI,
      1.09-3.44; P=0.02, respectively). Compared with other strong opioids, nausea and
      constipation occurred significantly less frequently with the use of oxycodone for
      cancer-related pain (OR=0.52, 95% CI=0.32-0.85, P=0.009; OR= 0.55, 95% CI= 0.35
      0.87, P= 0.01; respectively). In conclusion, this meta-analysis confirms that the
      efficacy and tolerability of oxycodone are superior to those of other strong
      opioids, including morphine sulfate, codeine and tramadol, supporting its use as
      an opioid for cancer-related pain.

PMID- 22970031
TI  - Inhibition of proliferation of human lung cancer cells by green tea catechins is
      mediated by upregulation of let-7.
AB  - Green tea catechins are known to function as anticancer agents via inhibition of
      carcinogenesis during the initiation, promotion and progression stages. Many
      potential mechanisms have been proposed, yet the precise mechanism of lung cancer
      prevention by green tea catechins remains unclear. microRNAs (miRs) are a class
      of 21-24 nucleotide small non-coding RNAs and play critical roles throughout
      cellular development and regulation. Emerging evidence demonstrates that tea
      catechins influence the expression of miRs in human cancer cells to inhibit
      tumorigenesis. Both let-7a-1 and let-7g were detected in the human lung cancer
      cells treated with tea catechins. The cell viability and cell cycle were analyzed
      after tea catechins treatment. In the present study, we found that tea catechins
      upregulated the tumor-suppressor miRs, let-7a-1 and let-7g, in lung cancer cell
      lines. The upregulation of let-7a/7g repressed the expression of their targets, C
      MYC and the regulatory protein of LIN-28, at the mRNA and protein levels.
      Moreover, the cell growth assay indicated that tea catechins significantly
      inhibited cell proliferation, and the flow cytometric analysis revealed an
      increase in the number of cells in the G2/M phase and a decrease in the number of
      cells in the S phase after treatment with tea catechins. These observations
      suggest that green tea catechins mediate the inhibition of proliferation of lung
      cancer cells through the let-7 signaling pathway.

PMID- 22970032
TI  - Relationship between XRCC1 and XPD polymorphisms and the risk of the development
      of hepatocellular carcinoma: A case-control study.
AB  - Hepatocellular carcinoma (HCC) is a serious public health issue, the incidence of
      which is considered to be closely related to tobacco smoking, alcohol
      consumption, hepatitis B virus (HBV) infection and family history. The DNA repair
      system is an important protective mechanism against the development of malignant
      cells induced by internal and external environmental factors. The aim of this
      study was to investigate the association of polymorphisms of XRCC1-194, XRCC1-280
      and XPD-312 DNA repair genes and the risk of development of HCC in Han Chinese
      patients. A case-control design was used including 252 HCC inpatients and 250
      healthy controls recruited and matched by age, gender, tobacco smoking, alcohol
      consumption, HBV infection and family history. XPD Asp312Asn, XRCC1 Arg194Trp and
      XRCC1 Arg280His genes were examined using a sequencing assay method.
      Distributions of the genotype frequency and odds ratio (OR) between the two
      groups were analyzed. The results demonstrated that there was no significant
      difference in the frequencies of XPD Asp312Asn, XRCC1 Arg194Trp and XRCC1
      Arg280His in the HCC cases and the control group. In the stratified analysis of
      different allele genotypes, the frequency of the XRCC1-194 site genotype was not
      significantly different between the case and control group. The presence of the
      XRCC1 280His genotype was associated with a significantly increased risk of HCC
      under conditions of HBV infection and family history [OR (95% CI): 1.68 (1.08
      2.60), 4.20 (1.34-13.20), respectively]. Similarly, the XPD 312Asn significantly
      increased the risk of HCC under conditions of alcohol consumption, tobacco
      smoking, HBV infection and family history [OR (95% CI): 1.67 (1.10-2.60), 1.87
      (1.18-2.96), 1.96 (1.24-3.10), 3.40 (1.32-8.76), respectively]. In conclusion,
      tobacco smoking and alcohol consumption are high risk factors of HCC for the XPD
      312Asn genotype; HBV infection and family history increase the risk of HCC for
      the genotypes XRCC1 280His and XPD 312Asn.

PMID- 22970033
TI  - Significance of ABCA1 in human carotid atherosclerotic plaques.
AB  - The ATP-binding cassette transporter A1 (ABCA1) is an important effector in the
      regulation of cholesterol efflux from cells. In this study, we assessed the role
      of ABCA1 in human carotid atherosclerotic plaques (CAPs). We found that ABCA1 and
      retinoid X receptor alpha (RXRalpha) mRNAs were significantly increased in the
      atherosclerotic plaques compared to control arteries. The increased ABCA1 mRNA
      correlated with that of RXRalpha in plaques. According to the modified American
      Heart Association plaque classification, atherosclerotic specimens were assigned
      to three grades, and ABCA1 and RXRalpha mRNA levels were compared across plaques
      of different grades. Resultantly, plaques of grade II and III exhibited higher
      mRNA levels than grade I, but there was no difference in mRNA levels between
      plaques of grade II and III. By contrast, ABCA1 and RXRalpha protein levels were
      notably reduced in plaques relative to control tissues. Similarly, plaques of
      grade II and III exhibited lower ABCA1 and RXRalpha protein levels than grade I,
      and there was no difference in protein levels between plaques of grade II and
      III. Our findings suggest that decreased ABCA1 protein plays a key role in the
      pathogenesis of CAP; the regulation of ABCA1 may be mediated by RXRalpha and
      ABCA1 mRNA levels may serve as an indicator for plaque stability.

PMID- 22970034
TI  - Combination of simvastatin and bone morphogenetic protein-2 enhances the
      differentiation of osteoblasts by regulating the expression of phospho-Smad1/5/8.
AB  - Statins inhibit 3-hydroxy-3-methylglutarylcoen zyme A reductase, which catalyzes
      the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a rate
      limiting step in cholesterol synthesis. A number of studies have demonstrated
      bone-promoting effects when simvastatin is applied locally with different
      carriers in various animal models. In the prsent study, the dose-dependent impact
      of simvastatin and bone morphogenetic protein-2 (BMP-2) on the cellular
      proliferation and differentiation of osteopre-cursor cells was evaluated. The
      alkaline phosphatase activity (ALP) test was performed to assess differentiation,
      and protein expression related to bone formation, including that of phospho
      Smad1/5/8 (pSmad1/5/8), was measured using western blot analysis to evaluate the
      underlying mechanism(s). Cultures grown in the presence of 0.1 MUM simvastatin
      with 60 ng/ml BMP-2 exhibited the highest value for ALP activity. The results of
      the western blot analysis indicated that the addition of simvastatin upregulated
      pSmad1/5/8 expression and the combination of 0.1 MUM simvastatin and 60 ng/ml BMP
      2 produced a significant increase in protein expression. Based on these findings,
      it was concluded that the combination of simvastatin and BMP-2 produced positive
      effects on the differentiation of osteoprecursor cells. The results also suggest
      that the combination of simvastatin and BMP-2 has synergistic effects that are
      achieved through the BMP pathway by enhancing the expression of pSmad1/5/8
      expression.

PMID- 22970035
TI  - Endoluminal treatment for venous vascular complications of malignant tumors.
AB  - The aim of this study was to explore the efficacy and safety of interventional
      treatment for venous vascular complications of malignant tumors. Sixty-one
      patients with venous vascular complications of malignant tumors were treated from
      May 2002 to May 2009; 37 men and 24 women with mean age 57.8 years (33-82 years).
      Lesions included acute deep vein thrombosis (n=18); venous stenosis or occlusion
      (n=32); tumor embolus in vein (n=11). The interventional therapeutic operations
      included vena cava filter implantation, trans-catheter thrombolytic therapy,
      recanalization, percutaneous transluminal angioplasty (PTA) and stenting. The
      success rate of thrombolysis and stent implantation, the clinical success rate,
      complications, recurrence rate of the treated region and survival duration were
      recorded. Eighteen patients accepted filter and thrombolytic therapy with a
      success rate of 100%; total urokinase dosage was 7.42+/-1.49 (4.5-10) million
      units. Symptoms disappeared (n=15), were palliated (n=3) and thrombi were
      completely dissolved (n=2), almost completely dissolved (n=8, >90%), partially
      dissolved (n=6, 50-90%) and not dissolved (n=2, <50%). No pulmonary embolism
      emerged after the operation. Forty-three patients accepted recanalization, PTA
      and stent therapy with a success rate of 95.3% (41/43). Symptoms disappeared
      (n=25), were palliated (n=16) and did not change (n=2) 3 days following the
      operation. There were no severe complications during the procedure. During follow
      up, 12 patients again suffered symptoms of venous occlusion and 47 patients died
      of tumor aggravation without symptom recurrence. As a result, interventional
      therapy has advantages including smaller injuries, well tolerance, high success
      rate, quick palliation of symptoms and superior clinical efficacy in the
      treatment of venous vascular complications for malignant tumors.

PMID- 22970037
TI  - Mesenchymal stem cell-like cells in classic renal angiomyolipoma.
AB  - As a benign mesenchymal tumor, classic renal angiomyolipoma (AML) may obliterate
      the kidney parenchyma and cause renal hemorrhage. It has previously been reported
      that mesenchymal stem cells (MSCs) are involved in tumorigenesis; however, there
      have been no studies on stem cells with renal AML origin. In the present study,
      six females with classic renal AML received a partial or total nephrectomy.
      During surgery, tumor tissues were collected and culture expansion of adhesive
      fibroblastoid cells from these tissues was performed. We successfully isolated
      and cultured MSC-like cells from all six renal AML tumors. MSC characteristics,
      including morphology, immunophenotype and multidifferentiation potential were
      analyzed. Flow cytometry analysis revealed that these cells are highly similar to
      human bone marrow MSCs due to the expression of MSC-specific surface proteins,
      including CD29, CD44, CD73, CD90 and CD105. The stem cell-like nature of these
      cells is further supported by their adipogenic and osteogenic differentiation
      potentials when incubated in appropriate differentiation cocktails. Renal AML
      derived adhesive cells possessing the characteristics of MSCs are described for
      the first time. They are a novel cell type which may be useful in future studies
      with regards to determining the role of stem cells in the formation and
      development of renal AML.

PMID- 22970036
TI  - Synchronous primary corpus and ovarian cancer: High incidence of endometriosis
      and thrombosis.
AB  - In an attempt to clarify the clinical characteristics of synchronous primary
      endometrial and ovarian cancer (SPC), we reviewed the clinicopathological
      features of 13 cases treated in the Department of Gynecology and Obstetrics at
      Kyoto University Hospital over the last 6 years and compared them with 186 cases
      of primary uterine corpus cancer (PCC) and 136 cases of primary ovarian cancer
      (POC). Comparisons were performed based on clinicopathological factors, including
      age, BMI, parity, complication of thrombosis and FIGO stage. For SPC patients,
      the mean age was 51.5 years; 6 (46%) were nulliparous, and 7 (53%) had
      complicated thrombosis. All had well-differentiated endometrial cancer and 12
      (92%) had endometrioid cancer in the ovary. The mean age of the SPC patients was
      significantly lower than that of the PCC patients (51.5 vs. 58.9 years).
      Thrombosis occurred in the SPC patients at a significantly higher rate than in
      both the PCC and POC patients. When the incidence of endometriosis and the
      regularity of menstruation were compared between patients who developed SPC with
      those who develop PCC at a young age (under 45 years), the SPC patients exhibited
      a significantly higher rate of endometriosis (100 vs. 35%), whereas the PCC
      patients exhibited a higher rate of irregular menstruation (53 vs. 15%, p=0.05).
      As for thrombosis, the age and FIGO stage of thrombosis-positive patients were
      significantly higher than those of thrombosis-negative patients in PCC and POC,
      while in SPC patients there was no such difference. In conclusion, this study
      demonstrated the differences in clinical features between SPC and PCC, and also
      novel features of SPC, namely endometriosis and thrombosis, which are essential
      in the management of this disease.

PMID- 22970038
TI  - Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells.
AB  - In our previous study, we reported that the cannabinoid receptors CB1 and CB2 are
      overexpressed in human hepatocellular carcinoma (HCC) tissues. Recently, the
      antitumor potential of the endogenous cannabinoid anandamide (AEA) has also been
      addressed. The present study was conducted to investigate the anti-proliferative
      effects of AEA in HCC cells. The human HCC cell line Huh7 was used. Cell
      proliferation was measured by MTT assay and flow cytometry. Apoptotic analysis
      was investigated by TUNEL assay. Real-time PCR and western blot analysis were
      used to analyze the expression of relevant molecules. The results of this study
      demonstrated that AEA inhibited the proliferation of Huh7 cells, resulted in G1
      cell cycle arrest and induced apoptosis. Furthermore, downregulation of CDK4 and
      upregulation of p21 and Bak by AEA were observed. This study defines the anti
      proliferative effects of anandamide in HCC cells and suggests that AEA has
      therapeutic potential in the management of HCC patients.

PMID- 22970039
TI  - Clinical significance of GADD153 expression in stage I non-small cell lung
      cancer.
AB  - The transcription factor growth arrest and DNA damage-inducible gene 153
      (GADD153), also known as CHOP, is considered to function as a proapoptotic
      molecule. Overexpression of GADD153 leads to cell cycle arrest and/or apoptosis.
      However, its clinical implications in non-small cell lung cancer (NSCLC) remain
      controversial. Therefore, we investigated the expression of GADD153 in stage I
      NSCLC using immunohistochemistry. Paraffin-embedded tissue sections from 76
      patients, who were diagnosed with primary stage I NSCLC and had undergone a
      curative lung resection, were stained using an anti-GADD153 antibody. The
      intensity of GADD153 immunostaining was evaluated within the cell membrane and
      cytoplasm of invasive cancer components. The correlation between the intratumoral
      expression of GADD153 and various clinical parameters were explored. GADD153 was
      detected in 29 (38.2%) cases. No statistically significant difference in
      expression was demonstrated between stage IA and stage IB tumors (35.0 vs. 39.3%;
      P=0.735). The expression of GADD153 was not affected by histological subtypes or
      histological grades of differentiation. The intratumoral expression of GADD153
      did not influence the overall survival rate (53.29 vs. 52.18 months; P=0.743) or
      disease-free survival rate (46.97 vs. 54.19 months; P=0.084) of stage I NSCLC
      patients. However, patients with GADD153 expression demonstrated an improved
      disease-specific survival rate (28.80 vs. 53.85 months; P=0.020). No patients
      with GADD153 expression demonstrated distant metastasis (P=0.029). These data
      suggest that GADD153 expression may be a valuable prognostic factor of early
      stage NSCLC in patients who have undergone curative lung resection.

PMID- 22970040
TI  - Wide local excision and reconstructive surgery of desmoid tumour of the crus
      (Case report).
AB  - Extra-abdominal desmoid tumour is a rare type of tumour which is conventionally
      treated with wide local excision. However, wide local excision usually causes
      irreparable damage to the limbs. Nevertheless, few patients have been subjected
      to wide local excision and reconstructive surgery in a single procedure. A 52
      year-old female reported a slow-growing lump in the right crus which had been
      growing for two years. The patient complained of persistent pain, especially at
      night, and was first subjected to lump resection in another hospital. The
      postoperative histopathological examination indicated muscle fibroma. Three
      months later, the lump recurred in the same position. The persistent pain induced
      by the tumour hampered her ability to walk. Wide local excision was conducted on
      the major parts of the gastrocnemius and soleus. After the pathological
      examination confirmed that the resection margin was negative, we performed
      reconstructive surgery on the Achilles tendon. The patient recovered
      plantarflexion function following the surgery and did not report any recurrence
      in the 6-year follow-up period. The desmoid tumour is a low-grade malignant
      tumour. Thus, the main focus of the treatment is to restore the function of the
      limbs to optimal capacity, such that the incidence of tumour recurrence is
      minimised.

PMID- 22970041
TI  - Effect of the tumor suppressor gene ING4 on the proliferation of MCF-7 human
      breast cancer cells.
AB  - Inhibitor of growth 4 (ING4) is a member of the ING family and acts as a tumor
      suppressor protein. To investigate the impact of ING4 on breast cancer
      proliferation, the present study examined the antitumor effects caused by
      upregulation in the expression of ING4 and its possible mechanism of effect in
      MCF-7 cells. A plasmid-based expression system encoding the ING4 gene was used to
      construct a stable cell line and overexpress ING4 in MCF-7 cells. Real-time PCR
      and western blot analysis were used to detect the mRNA and protein expression
      levels of ING4, respectively. Cell growth was examined by
      methylthiazolyltetrazolium (MTT) assay. Cell cycle distribution and cell
      apoptosis were measured by flow cytometry. The expression of p21, p53 and bax
      genes were tested by real-time PCR and western blot analysis. The stably
      transfected cell lines pcDNA3.1(+)/ING4 (with the ING4 gene) and pcDNA3.1(+) (an
      empty vector) were established. The expression levels of ING4 mRNA and protein in
      the stable cell line expressing pcDNA3.1(+)/ING4 were significantly higher than
      those of the two control cell lines. The cell proliferation of stably transfected
      cells was inhibited, and the inhibitory rate was 62.58+/-2.93%. Based on the
      changes in cell cycle distribution in stably transfected cells compared with two
      control cell lines, a number of cells were blocked in the G0/G1 phase 67.82+/
      3.78% (P<0.05). In addition, the apoptotic rate was significantly higher, at
      31.51+/-3.02% (P<0.05). Real-time PCR revealed that p21 and bax mRNA expression
      were increased (P<0.01), but the expression of p53 did not change significantly
      (P>0.05) in the stably transfected cell lines. Western blot analysis results of
      p21, bax and p53 were in accordance with real-time PCR results. ING4 upregulation
      may inhibit breast cancer cell proliferation and accelerate the process of
      apoptosis. It is suggested that ING4 plays a significant role in the suppression
      of breast cancer progression.

PMID- 22970042
TI  - The binding characteristics of a cyclic nonapeptide, c(CGRRAGGSC), in LNCaP human
      prostate cancer cells.
AB  - Previous studies have demonstrated that interleukin-11 (IL-11) and the IL-11
      receptor (IL-11R) are associated with the regulation of tumor progression and may
      play a significant role in bone metastases. The nonapeptide structure
      c(CGRRAGGSC) is a phage display-selected IL-11 mimic, which binds to IL-11R. The
      aim of this study is to investigate the binding characteristics of a cyclic
      nonapeptide c(CGRRAGGSC) in LNCaP human prostate cancer cells. To investigate its
      binding and uptake effects, c(CGRRAGGSC) was labeled with a fluorescent dye,
      LSS670. The binding location of LSS670 cyclic nonapeptide in LNCaP cells was
      investigated by fluorescence microscopy. Flow cytometry was used to detect the
      fluorescence of LSS670-c(CGRRAGGSC) in LNCaP cells. The binding of LSS670
      c(CGRRAGGSC) in LNCaP cells was inhibited by unlabeled cyclic nonapeptide,
      depending on the varying density of c(CGRRAGGSC) and different time points. The
      molecular probe bound to the LNCaP cell membrane and cytoplasm through
      fluorescence tracing. In the saturation experiments performed in vitro, the K(d)
      value was 3.2+/-0.02 nM and the B(max) value was 754+/-34 fmol/mg.pro. The 50%
      inhibiting concentration (IC(50)) was 6.31+/-0.12 nmol/l and the K(i) value was
      2.11+/-0.14 nmol/l in competitive inhibition experiments. Our results suggest
      that c(CGRRAGGSC) is able to specifically bind to LNCaP cells through a receptor
      mediated pathway.

PMID- 22970043
TI  - Response to postoperative radiotherapy as a prognostic factor for patients with
      low-grade gliomas.
AB  - Due to the favorable natural history in patients with low-grade gliomas (LGGs),
      there is no consensus on the treatment strategy following maximal safe surgical
      resection. A number of studies have been conducted to identify prognostic factors
      in patients treated for LGG. The present study evaluated the treatment outcomes
      as well as prognostic factors and their impact on overall survival (OS) and
      disease-free survival (DFS). We retrospectively reviewed 30 consecutive patients
      treated for LGG at the Department of Radiotherapy from February 2008 to July
      2011. The patients underwent surgical intervention and postoperative
      radiotherapy. The response to radiotherapy was evaluated from six to eight weeks
      after the end of treatment using MRI analysis. Kaplan-Maier analysis was used for
      OS and DFS estimation. The endpoint was mortality as a result of any cause.
      Within a median follow-up of 21.8 months, 9 patients (30%) with disease
      progression were reported. The two- and five-year DFS and OS was 85.2 and 68.3%
      for DFS, and 84.3 and 63.4% for OS, respectively. The response to radiotherapy,
      evaluated in an MRI study, was found to be highly correlated with OS (p<0.0001).
      We also observed a significantly higher OS in patients with disease progression
      treated with salvage chemotherapy after the end of radiotherapy (p=0.08).
      Improved outcome among patients with LGG may be predicted by response to
      radiotherapy evaluated by MRI following termination of treatment.

PMID- 22970044
TI  - Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of
      WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model.
AB  - Acute myeloid leukaemia results from the neoplastic transformation of
      haematopoietic stem cells. Although advances have been made in its treatment, the
      mortality rate remains high. As a result, therapeutic alternatives continue to be
      explored. In this study, we present evidence that suggests that casein, the
      principal protein in milk, possesses significant antileukaemic properties. We
      investigated whether casein inhibited the in vitro proliferation and induced the
      apoptosis of the mouse myelomonocytic leukaemia cell line WEHI-3. By contrast,
      under identical conditions, casein markedly promotes the proliferation of mouse
      normal mononuclear bone marrow cells. Since the selective elimination of
      leukaemia cells is an ideal therapeutic strategy, we also evaluated the
      antileukaemic potential of casein in vivo. The results showed that casein
      increases the survival of mice bearing WEHI-3-induced tumours, suggesting that
      this molecule is also capable of inhibiting the proliferation of these cells in
      vivo. The evidence that casein inhibited cell proliferation and induced apoptosis
      in leukaemia cells in vitro, but increased survival in vivo in a leukaemia mouse
      model, indicates that casein may be useful in leukaemia therapy.

PMID- 22970045
TI  - Factors associated with hepatic dysfunction in hepatitis B-positive patients with
      postgastrectomy adenocarcinoma.
AB  - In the present study, we reviewed 44 postgastrectomy adenocarcinoma patients who
      had hepatitis B and received treatment in the Abdominal Cancer Department of the
      West China Hospital between October 2006 and October 2010. Of these patients, 17
      developed hepatic dysfunction. Radiotherapy is an independent risk factor to
      hepatic function on univariate and multivariate analysis. Grade III or IV hepatic
      dysfunction was developed by five patients, all of whom had received radiotherapy
      and had reactivated hepatic B virus (HBV). Radiotherapy is a significant risk
      factor to hepatic function in patients with postgastrectomy adenocarcinoma
      carrying HBV, thus we suggest excluding the liver from the radiation field. HBV
      reactivation plays a role in the development of grade III or IV hepatic
      dysfunction. Patients with reactivated HBV should immediately receive regular
      antiviral treatment.

PMID- 22970046
TI  - Treatment of a GIST patient with modified dose of sunitinib by measurement of
      plasma drug concentrations.
AB  - In this study we report the pharmacokinetics and severe adverse effects of
      sunitinib in a woman with a gastrointestinal stromal tumor (GIST). A 60-year-old
      woman with small intestinal GIST developed severe thrombocytopenia
      (1.7*10(4)/MUl) following 1 week of treatment with sunitinib at 50 mg/day.
      Although the dose of sunitinib was reduced to 25 mg/day, platelet levels remained
      low. On day 7, the trough concentration of sunitinib plus SU12662 was 46.1 ng/ml
      and the area under the curve (AUC) was 1,393.0 ng.h/l. The dose was again reduced
      to 12.5 mg/day. However, the day after resumption of treatment, the patient
      developed symptoms of left heart failure due to myocardosis caused by sunitinib.
      Sunitinib has been reported to inhibit platelet-derived growth factor receptor
      (PDGFR) phosphorylation at concentrations over the range of 50-100 ng/ml
      (sunitinib plus SU12662) in vivo. In this case, the plasma concentration was
      sufficient to inhibit PDGFR at 25 or 50 mg/day. However, thrombocytopenia
      appeared at both dosages. Although the results in this case did not suggest a
      correlation between thrombocytopenia and plasma concentration, the degree of
      thrombocytopenia was decreased by reduction of the dose. In conclusion, the
      findings reported here indicate that the plasma concentration of sunitinib plus
      SU12662 is an important indicator to reduce adverse effects.

PMID- 22970047
TI  - The promoter methylation of the Syk gene in nasopharyngeal carcinoma cell lines.
AB  - The aim of this study was to investigate the mRNA and protein expression levels
      of the Syk gene as well as its promoter methylation in nasopharyngeal carcinoma
      (NPC) cell lines. The CNE-1 (highly differentiated), CNE-2 (poorly
      differentiated) and NP69 (non-cancerous human immortalized nasopharyngeal
      epithelial cells) cell lines were used in the present study. The MS-PCR, Q-RT-PCR
      and western blotting methods were used to examine the Syk gene promoter
      methylation levels and mRNA and protein expression in the three cell lines. The
      promoter methylation levels in CNE-1, CNE-2 and NP69 cells were 36%, 62% and 0,
      respectively. The mRNA levels in CNE-1 and CNE-2 cells were 42+/-3.5 and 28+/-2%
      of that in NP69, respectively; the protein levels in CNE-1 and CNE-2 cells were
      36+/-4.5 and 16+/-2.5 of that in NP69, respectively; the statistical differences
      between groups were significant. The lower differentiation levels of the NPC cell
      lines correlate with lower levels of mRNA and protein expression of the Syk gene,
      as well as higher promoter methylation levels.

PMID- 22970048
TI  - Volume doubling time of lung cancers detected in a chest radiograph mass
      screening program: Comparison with CT screening.
AB  - The aim of this study was to evaluate the volume doubling time (VDT) of lung
      cancer detected in our annual chest radiograph screening program and to compare
      it with those previously reported for computed tomography (CT) screening. In
      total, 209 patients who had a measurable tumor shadow and a history of
      participating in our chest radiograph mass screening program between 2006 and
      2009 were included in this study. Indirect roentgenograms for patients with lung
      cancer were converted into digital images, and the section showing the tumor was
      enlarged on the monitor to a size of 0.01 mm. The mean VDT for all the patients
      was 158 days. Only 3.8% of the patients had a VDT of more than 400 days. In 140
      patients with adenocarcinoma, the mean VDT was 177 days, and 5.0% of these
      patients had a VDT of more than 400 days. In the 44 patients with squamous cell
      carcinoma, the mean VDT was 133 days, and only 2.3% of these patients had a VDT
      of more than 400 days. These results were different from those previously
      reported for CT screening. In several reports on CT screening, more than 20% of
      the lung cancers had VDTs of more than 400 days. Since it is common knowledge
      that there are 'indolent' lung cancers with a VDT of more than 400 days,
      screening by annual chest radiography with rare overdiagnosis may need to be
      reconsidered.

PMID- 22970049
TI  - Gastric and colonic metastases from primary lung adenocarcinoma: A case report
      and review of the literature.
AB  - Lung cancer is one of the leading causes of cancer-related mortality worldwide.
      Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports
      have been published and the majority of described metastatic sites involved the
      small intestine. In the present study, we report the first case of primary lung
      adenocarcinoma with both gastric and colonic metastases. We also review the
      published literature of primary lung cancer with gastrointestinal metastasis.

PMID- 22970050
TI  - Superselective internal iliac arterial embolization for severe hemorrhage
      following radical prostatectomy.
AB  - Severe hemorrhage following a prostatectomy is a rare and serious complication. A
      63-year-old male with severe hemorrhage following radical prostatectomy which led
      to hypovolemic shock presented at our department and was treated with
      superselective internal iliac arterial embolization. At 6 months follow-up, the
      patient had recovered well, regained excellent urinary continence and the pelvic
      hematoma was absorbed using ultrasound examination. We concluded that rapid
      diagnosis by computed tomography angiography and early superselective
      embolization of internal iliac artery should be considered as the treatment of
      choice in severe hemorrhage cases following radical prostatectomy.

PMID- 22970051
TI  - Synergistic cytotoxic effects of recombinant human adenovirus p53 and radiation
      at various time points in A549 lung adenocarcinoma cells.
AB  - The aim of this study was to evaluate the effects of recombinant human adenovirus
      p53 (rAd-p53; Gendicine) transfection and radiation at various time points
      following transfection. Cytotoxic effects and p53 protein expression levels were
      analyzed. rAd-p53 containing the human wild-type p53 gene was introduced into the
      human lung adenocarcinoma cell line A549, and cells were irradiated with a single
      dose of 6 MeV 4 Gy beta rays. According to the time interval between rAd-p53
      transfection and radiotherapy (RT), A549-transfected rAd-p53 cells were divided
      into 5 groups: radiation administered immediately after transfection (0 h-RT)
      group, after 3 h group (3 h-RT), after 6 h group (6 h-RT), after 24 h group (24 h
      RT) and after 48 h group (48 h-RT). Cells with rAd-p53 transfection alone (Ad
      p53) and with empty adenovirus (Ad) were included as the two control groups.
      Following 72 h of transfection, cell viability and growth were analyzed using MTT
      assays and flow cytometry, and p53 protein expression was analyzed using western
      blot analysis. From 0 h-RT to 48 h-RT, cell viability gradually decreased, while
      percentage of apoptotic cells and p53 protein expression gradually increased. The
      cell viability suppression rates in the 6 h-RT, 24 h-RT and 48 h-RT groups were
      56.7+/-5.4, 60.8+/-6.0 and 68.9+/-6.6, respectively, which were significantly
      greater compared to that of the Ad-p53 (40.8+/-4.7), 0 h-RT (45.0+/-3.5) and 3 h
      RT groups (47.0+/-4.3). No statistically significant differences were observed in
      the cell viability suppression rates among the 6 h-RT, 24 h-RT and 48 h-RT groups
      (P>0.05). Similar changes were observed in the percentage of apoptotic cells. The
      p53 protein expression level in the 6 h-RT group (0.856+/-0.092) was higher
      compared to that in the 3 h-RT group (0.643+/-0.089) (t=2.882; P=0.045), but not
      significantly different from that of the 24 h-RT group (1.193+/-0.202). The cell
      viability suppression rate and percentage of apoptotic cells was positively
      correlated with p53 protein expression in the A549 cells (P<0.05). Radiation may
      inhibit or damage p53 protein expression at the early stage of rAd-p53
      transfection. To sensitize tumor cells to irradiation and achieve maximal
      cytotoxic effects, it is recommended to conduct RT at least 6 h following
      transfection with rAd-p53.

PMID- 22970052
TI  - Expression of keratin 20 and its clinicopathological significance in intrahepatic
      cholangiocarcinoma.
AB  - Although the expression of keratin 7 (K7) and K20 is considered to be a useful
      factor in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and
      metastatic colorectal carcinoma (CRC) of the liver, a proportion of typical ICC
      retains K20 expression. The frequency and biological significance of K20
      expression in ICC remains unclear. We analyzed the expression of K7, K19 and K20
      in 66 surgically resected liver tumors consisting of 46 ICCs and 20 metastatic
      CRCs of the liver and 20 corresponding primary CRCs. In the 46 ICCs, K7, K19 and
      K20 were expressed in 40 (87%), 45 (98%) and 16 (35%) cases, respectively. K7,
      K19 and K20 were expressed in 1 (5%), 20 (100%) and 16 (80%) of the 20 primary
      CRCs and 2 (10%), 20 (100%) and 16 (80%) of the 20 metastatic CRCs, respectively.
      A combined K7/K20 profile was identified as a good predictor for differentiating
      ICC and metastatic CRC. K20 expression in ICC was significantly associated with
      male gender (P=0.034), hilar location (P=0.026), intraductal papillary type
      (P=0.006), intestinal phenotype (P<0.001) and MUC2 expression (P=0.008).
      Univariate analysis identified that poor patient survival was significantly
      associated with histological grade (P=0.020), invasion depth (P=0.005), lymph
      node metastasis (P=0.012), tumor stage (P=0.004) and vessel invasion (P=0.023).
      The tumor stage (P=0.002) was a poor independent prognostic indicator, while MUC6
      expression (P=0.036) was a good independent prognostic indicator. The survival
      rate in patients with K20-positive ICC was lower compared to that of patients
      with K20-negative ICC, but was not statistically significant. Furthermore, the
      combined K7/K20 immunophenotype was identified to be useful for differentiating
      ICC and metastatic CRC. K20-positive ICC displays specific characteristics with
      regards to tumor location and histological subtype. Additionally, MUC6 expression
      in ICC is a good independent prognostic factor, while K20 expression is more
      often associated with aggressive biological behavior.

PMID- 22970054
TI  - The promoter methylation and expression of the O6-methylguanine-DNA
      methyltransferase gene in uterine sarcoma and carcinosarcoma.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) gene promoter hypermethylation is
      observed in a number of solid tumors and is correlated with the silencing of MGMT
      expression. In glioblastoma patients treated with the alkylating agent
      temozolomide, MGMT gene methylation status was shown to have predictive value in
      terms of prolonged overall survival. Recently, temozolomide has demonstrated
      promising activity in the treatment of soft tissue sarcomas, including those of
      the uterus. The tissue specimens involving tumor samples and normal uterine
      fragments were obtained from nine patients with smooth muscle uterine sarcoma, 11
      with stromal uterine sarcoma and 17 with mixed uterine tumors. MGMT gene promoter
      methylation was analyzed by combined bisulfite restriction analysis (COBRA) while
      its expression levels were assessed using the real-time reverse transcription
      polymerase chain reaction (qRT-PCR). MGMT promoter methylation was observed in
      27% of all tumor samples analyzed. When stratified by the disease type, 55.5%
      (5/9) of smooth muscle sarcomas, 23.5% (4/17) of mixed uterine tumor tissues and
      9% (1/11) of stromal sarcomas showed MGMT methylation. The MGMT promoter
      methylation was associated with lower levels of gene expression in tumors when
      compared with those with an unmethylated promoter (P=0.0232) or normal tissues
      (P=0.0141). To conclude, MGMT promoter methylation and downregulation of gene
      expression is observed in a fraction of carcinosarcomas and non-epithelial
      malignant tumors of corpus uteri. The assessment of MGMT promoter methylation
      status may potentially identify patients who would benefit from temozolomide
      treatment.

PMID- 22970053
TI  - Central nervous system involvement in adult patients with diffuse large B-cell
      lymphoma: Influence of rituximab.
AB  - CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like
      chemotherapy, in combination with rituximab (R-CHOP-like), improves outcome in
      patients with diffuse large B-cell lymphoma (DLBCL). We aimed to investigate the
      impact of rituximab on central nervous system (CNS) disease in adult patients. We
      studied 315 patients (aged 18-60 years old) from six hospitals between July 2003
      and May 2008. All patients received CHOP-like (n=165) or R-CHOP-like (n=150)
      regimen every 3 weeks. With a median follow-up of 3.69 years, 10 patients (3.17%)
      developed CNS disease. The cumulative risk of CNS occurrence was not
      significantly different between the two treatment groups (P=0.871). We conclude
      that the addition of rituximab did not reduce the risk of CNS disease in adult
      patients with DLBCL.

PMID- 22970055
TI  - Evaluation of microsatellite instability in women with epithelial ovarian cancer.
AB  - The function of microsatellite instability (MSI) and the optimal panel of markers
      for epithelial ovarian cancer (EOC) are not well established. This study aimed to
      use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and
      D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma,
      compared with ovarian serous cystadenoma and normal ovaries. A total of 37
      patients were divided into three groups, as follows: cystadenocarcinoma (n=13),
      cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and
      quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction
      (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging
      was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group.
      Polymorphisms were found using at least one marker in 32 women, and were observed
      with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26
      (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346
      and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of
      patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30%
      of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary
      group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the
      cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was
      detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the
      cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency
      of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was
      high, as well as in EOC, with no statistically significant difference between the
      groups. This suggests that MSI may arise as a consequence of the ovulatory
      process, and not solely as a feature of malignant ovarian tumors.

PMID- 22970056
TI  - Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic
      nucleoside analogues.
AB  - Cytotoxic nucleoside analogues are widely used in cancer chemotherapy. We used
      the cytosine arabinoside (Ara-C)-resistant erythroleukaemia cell line K562 and
      the Ara-C-sensitive myeloid leukaemia cell line HL60 to examine the differential
      expression of molecular markers. We found increased expression levels of
      deoxycytidine kinase (dCK) and human equilibrative nucleoside transporter 1
      (hENT1) and decreased levels of multidrug resistance protein 5 (ABCC5) and
      ribonucleoside reductase subunit M1 (RRM1) expression in Ara-C-sensitive HL60
      cells. We previously established the pemetrexed (MTA)-resistant small cell lung
      cancer cell lines PC6/MTA-0.4 and PC6/MTA-1.6 and found that MTA-resistant cells
      are more sensitive to gemcitabine (GEM) and Ara-C compared with parental PC-6
      cells. We examined the molecular markers for GEM and Ara-C sensitivity in MTA
      resistant cells and found increased gene expression of dCK and hENT1.
      Furthermore, treatment with MTA resulted in increased expression of dCK and hENT1
      and decreased expression of ABCC5 and RRM1, concomitant with the alteration of
      the resistance to Ara-C in Ara-C-resistant K562 cells. These results provide
      evidence that the chemotherapeutic activity of the combination of MTA and
      cytotoxic nucleoside analogues is synergistic with regard to the alteration of
      metabolic molecules.

PMID- 22970057
TI  - The History of AOSR: Asian Oceanian Society of Radiology.

PMID- 22970058
TI  - Fine needle aspiration of lung lesion: Lateral and transpectoral approach.
AB  - A 69 year-old man presented with an incidental finding on radiograph of a lesion
      in the left upper lobe. CT indicated it was likely to be a neoplasm and CT-guided
      FNA was requested. The lesion was located medial to the scapula so a creative
      approach was utilised to gain access to the lesion. This study discusses the
      approach used and why it reduced patient risk compared to a more conventional
      procedure. The sample was positive for neoplasm and there were no complications
      arising from the procedure.

PMID- 22970059
TI  - Multislice CT of the head and body routine scans: Are scanning protocols adjusted
      for paediatric patients?
AB  - PURPOSE: To investigate whether the multislice CT scanning protocols of head,
      chest and abdomen are adjusted according to patient's age in paediatric patients.
      MATERIALS AND METHODS: Multislice CT examination records of paediatric patients
      undergoing head, chest and abdomen scans from three public hospitals during a one
      year period were retrospectively reviewed. Patients were categorised into the
      following age groups: under 4 years, 5-8 years, 9-12 years and 13-16 years, while
      the tube current was classified into the following ranges: < 49 mA, 50-99 mA, 100
      149 mA, 150-199 mA, > 200 mA and unknown. RESULTS: A total of 4998 patient
      records, comprising a combination of head, chest and abdomen CT scans, were
      assessed, with head CT scans representing nearly half of the total scans. Age
      based adjusted CT protocols were observed in most of the scans with higher tube
      current setting being used with increasing age. However, a high tube current (150
      199 mA) was still used in younger patients (0-8 years) undergoing head CT scans.
      In one hospital, CT protocols remained constant across all age groups, indicating
      potential overexposure to the patients. CONCLUSION: This analysis shows that
      paediatric CT scans are adjusted according to the patient's age in most of the
      routine CT examinations. This indicates increased awareness regarding radiation
      risks associated with CT. However, high tube current settings are still used in
      younger patient groups, thus, optimisation of paediatric CT protocols and
      implementation of current guidelines, such as age-and weight-based scanning,
      should be recommended in daily practice.

PMID- 22970060
TI  - Anatomical variations of pulmonary venous drainage in Thai people: multidetector
      CT study.
AB  - OBJECTIVE: To evaluate the patterns of pulmonary venous drainage into the left
      atrium and to determine the frequency of each variant of pulmonary venous
      anatomy. MATERIALS AND METHODS: After institutional review board approval (No.
      09JUL011148), 300 studies of thoracic multidetector computed tomography were
      retrospectively reviewed for the anatomical features of the pulmonary vein and
      its drainage pattern into the left atrium. The percentage of each pattern was
      calculated. RESULTS: The anatomy of pulmonary venous drainage in 300 patients
      (150 male and 150 female, mean age 60.16 years) showed some variation. In the
      right pulmonary vein, the most common drainage pattern was two ostia (90.33%),
      followed by three to five ostia (6.33%) and a single ostium (3.33%). There were
      one or two separate middle lobe vein ostia in groups of more than two openings.
      On the left side, there were two patterns; a single venous ostium (59%) was much
      more common than two ostia (41%). In both right and left pulmonary veins, there
      were five cases (2 male, 3 female) that had a single pulmonary venous ostium,
      bilaterally. However, there were only 17 cases (5.67%), out of 300 enrolled in
      this study, that had bilateral pulmonary venous ostial variations. CONCLUSION: A
      classification system to succinctly describe pulmonary venous drainage patterns
      was developed. In left-sided drainage, a single left pulmonary ostium was the
      most common variation. The right-sided venous drainage varied more in both number
      and pattern than those of the left side; nevertheless, bilateral pulmonary venous
      ostial variation was not frequently found.

PMID- 22970061
TI  - Dosimetric evaluation of radiation dose rate effect in respiratory gated
      intensity modulated radiation therapy.
AB  - PURPOSE: To investigate the dosimetric accuracy of the sliding window gated IMRT
      compared with the static treatment, using varying dose rates. MATERIALS AND
      METHODS: This study measured changes in output and diode array response with
      changing dose rate, verified the precision of the motion table, and measured
      changes in dose distribution accuracy with film and diodes at two depths with
      changing dose rate. During 4DCT (4 Dimensional Computed Tomography), the
      patient's respiratory signals and target motion were recorded and imported to the
      XY4D simulation table of SUN NUCLEAR Corporation to simulate the patient's
      respiration and tumour motion. A single field of each sliding window IMRT plan
      with 30o wedge and one for lung cancer were used in this study. Three irradiating
      conditions, static and moving target with and without gating, were applied to
      both plans. RESULTS: The standard deviations of output, with the dose rates
      changing from 300-600 MU/min, were 0.065 cGy and 0.169 cGy for the ionisation
      chamber and diode, respectively. The verification of the motion table shows very
      good precision with 9.98 +/- 0.02 cm (true value = 10.0 cm). The measurements by
      MapCheck show the gamma index of the planned absolute dose distribution in static
      and moving targets with gating, resulting in more than 96% passing for all dose
      rates. The absolute dose distribution measured by film for the static target was
      agreeable with the value of moving target with gating. CONCLUSION: The sliding
      window gated IMRT technique is able to deliver an accurate dose to a moving
      target with the dose rate of 300-600 MU/min that is suitable for clinical
      treatment.

PMID- 22970062
TI  - Precocious puberty in children: A review of imaging findings.
AB  - OBJECTIVES: This review was aimed at determining the imaging findings in patients
      with precocious puberty. RESULTS: Within a period of 8 years (from 2002 to 2010)
      there were 53 patients diagnosed with precocious puberty. Out of the 53 patients,
      37 had undergone diagnostic imaging to detect the possible organic causes of
      precocious puberty. Imaging findings were positive in 31 patients and out of
      that, 3 patients had 2 findings each (34 abnormalities). Of the patients with
      positive imaging findings, central precocious puberty (gonadotrophin-dependent)
      was more common (81%; 25/31) and the causes included: tuber cinereum hamartoma (n
      = 10), glioma (n = 6), pineal gland tumour (n = 4), hydrocephalous (n = 3),
      arachnoid cyst (n = 2) and others (n = 3). Peripheral precocious puberty
      (gonadotrophin-independent) causes included: testicular adrenal rest tumour (n =
      3), adrenal carcinoma (n = 1), ovarian granulosa thecal cell tumour (n = 1), and
      tuberous sclerosis (n = 1). CONCLUSION: Positive imaging findings were observed
      in 84% (31/37) of the subjects. Hypothalamic hamartoma was the most common
      imaging finding in central precocious puberty while testicular adrenal rest
      tumour was the most common imaging finding in peripheral precocious puberty.

PMID- 22970063
TI  - Congenital renal anomalies detected in adulthood.
AB  - OBJECTIVE: To document the types of congenital renal anomalies detected in
      adulthood, the clinical presentation and complications of these renal anomalies,
      and the most useful imaging modality in detecting a renal anomaly. MATERIALS AND
      METHODS: This study was approved by the institutional review board and informed
      consent was waived. Between January 2007 and January 2011, the clinical data and
      imaging studies of 28 patients older than 18 years diagnosed with renal anomaly
      at the authors' institution were retrospectively reviewed. Renal anomalies in
      this study included only those with abnormality in position and in form. RESULTS:
      Of these 28 patients, 22 underwent imaging studies and their results constituted
      the material of this study. Of the 22 patients, 14 had horseshoe kidneys (HSK),
      four had crossed renal ectopia and four had malrotation. Sixteen patients were
      men and six were women. The patients ranged in age from 19 to 74 years (mean age
      51.1 years). Clinical presentations were abdominal pain (13), fever (13),
      haematuria (4), palpable mass (2), asymptomatic (2), polyuria (1) dysuria (1),
      blurred vision (1), and headache with weakness of left extremities (1). Imaging
      studies included abdominal radiograph (15), intravenous pyelography (IVP) (8),
      retrograde pyelography (RP) (4), ultrasonography (US) (7), and computed
      tomography (CT) (9). Associated complications included urinary tract stones (17),
      urinary tract infection (16), hydronephrosis (12), and tumours (2). Abdominal
      radiograph suggested renal anomalies in nine out of 15 studies. IVP, RP, US and
      CT suggested anomalies in all patients who had these studies performed. However,
      CT was the best imaging modality to evaluate anatomy, function and complications
      of patients with renal anomalies. CONCLUSION: HSK was the most common renal
      anomaly, with abdominal pain and fever being the most common presentations. UTI
      and stones were the most common complications. IVP, RP, US and CT can be used to
      diagnose renal anomalies but CT is the best imaging modality to evaluate renal
      anatomy, function and its complications.

PMID- 22970064
TI  - Dialysis catheter fibrin sheath stripping: a useful technique after failed
      catheter exchange.
AB  - Fibrin sheath formation around long-term haemodialysis catheter is a common cause
      of failed dialysis access. Treatment options include pharmacological and
      mechanical methods. This paper reports a case of failed dialysis access due to
      fibrin sheath encasement. Pharmacologic thrombolysis, mechanical disruption using
      guide wire and catheter exchange had failed to address the issue. Eventually,
      fibrin sheath stripping using the loop snare technique was able to successfully
      restore the catheter function.

PMID- 22970065
TI  - Social radiology: Where to now?
AB  - Radiology is a relatively high-cost and high-maintenance aspect of medicine.
      Expertise is constantly required, from acquisition to its use and quality
      assurance programmes. However, it is an integral part of healthcare practice,
      from disease diagnosis, surveillance and prevention to treatment monitoring. It
      is alarming that two thirds of the world is deficient in or lacks even basic
      diagnostic imaging. Developing and underdeveloped countries need help in
      improving medical imaging. Help is coming from various organisations, which are
      extending hands-on teaching and imparting knowledge, as well as training trainers
      to increase the pool of skilled practitioners in the use of imaging equipment and
      other aspects of radiology services. The scene for social radiology is changing
      and set to positively impact the world in the (near) future.

PMID- 22970066
TI  - Medical physics aspects of cancer care in the Asia Pacific region: 2011 survey
      results.
AB  - BACKGROUND: Medical physicists are essential members of the radiation oncology
      team. Given the increasing complexity of radiotherapy delivery, it is important
      to ensure adequate training and staffing. The aim of the present study was to
      update a similar survey from 2008 and assess the situation of medical physicists
      in the large and diverse Asia Pacific region. METHODS: Between March and July
      2011, a survey on profession and practice of radiation oncology medical
      physicists (ROMPs) in the Asia Pacific region was performed. The survey was sent
      to senior physicists in 22 countries. Replies were received from countries that
      collectively represent more than half of the world's population. The survey
      questions explored five areas: education, staffing, work patterns including
      research and teaching, resources available, and job satisfaction. RESULTS AND
      DISCUSSION: Compared to a data from a similar survey conducted three years ago,
      the number of medical physicists in participating countries increased by 29% on
      average. This increase is similar to the increase in the number of linear
      accelerators, showing that previously identified staff shortages have yet to be
      substantially addressed. This is also highlighted by the fact that most ROMPs are
      expected to work overtime often and without adequate compensation. While job
      satisfaction has stayed similar compared to the previous survey, expectations for
      education and training have increased somewhat. This is in line with a trend
      towards certification of ROMPs. CONCLUSION: As organisations such as the
      International Labour Organization (ILO) start to recognise medical physics as a
      profession, it is evident that despite some encouraging signs there is still a
      lot of work required towards establishing an adequately trained and resourced
      medical physics workforce in the Asia Pacific region.

PMID- 22970067
TI  - A rare case of an appendiceal mass masquerading as a pelvic tumour and causing
      bilateral hydronephrosis.
AB  - Diagnosing acute appendicitis in children can be difficult due to atypical
      presenting symptoms. While there are reported cases of acute appendicitis or
      appendiceal masses causing unilateral hydronephrosis, bilateral hydronephrosis as
      a complication of appendiceal mass is very rare. We report a case of a child who
      presented with cardinal symptomatology associated with the urogenital tract.
      Ultrasound (US) investigation showed a pelvic mass causing bilateral
      hydronephrosis. An initial diagnosis of a pelvic teratoma was made based on the
      US and computed tomography (CT) scan findings. The final diagnosis of an
      appendiceal mass causing bilateral hydronephrosis was established
      intraoperatively.

PMID- 22970068
TI  - Pelvic lipomatosis: US and CT diagnosis.

PMID- 22970070
TI  - Quality assurance of TomoDirect treatment plans using I'mRT MatriXX.
AB  - PURPOSE: To evaluate the performance of 2D-array I'mRT MatriXX for dose
      verification of TomoDirect treatment plans. METHODS: In this study, a 2D-array
      ion chamber device - the I'mRT MatriXX and Multicube Phantom from IBA - was used
      for dose verification of different TomoDirect plans. Pre-treatment megavoltage
      computed tomography (MVCT) was performed on the phantom setup for position
      correction. After the irradiation of treatment plans on the I'mRT MatriXX and
      Multicube Phantom, the measured doses of coronal planes were compared with those
      from the planning calculations for verification. The results were evaluated by
      comparing the absolute dose difference in the high dose region as well as the
      gamma analysis of the 2D-dose distributions on the coronal plane. The comparison
      was then repeated with the measured dose corrected for angular dependence of the
      MatriXX. RESULTS: When angular dependence is taken into account, the passing rate
      of gamma analysis is over 90% for all measurements using the MatriXX. If there is
      no angular dependence correction, the passing rate of gamma analysis worsens for
      treatment plans with dose contribution from the rear. The passing rate can be as
      low as 53.55% in extreme cases, i.e. where all doses in the treatment plan are
      delivered from the rear. CONCLUSION: It is important to correct the measured dose
      for angular dependence when verifying TomoDirect treatment plans using the
      MatriXX. If left uncorrected, a large dose discrepancy may be introduced to the
      verification results.

PMID- 22970069
TI  - Effective connectivity between superior temporal gyrus and Heschl's gyrus during
      white noise listening: linear versus non-linear models.
AB  - PURPOSE: This fMRI study is about modelling the effective connectivity between
      Heschl's gyrus (HG) and the superior temporal gyrus (STG) in human primary
      auditory cortices.  MATERIALS #ENTITYSTARTX00026; METHODS: Ten healthy male
      participants were required to listen to white noise stimuli during functional
      magnetic resonance imaging (fMRI) scans. Statistical parametric mapping (SPM) was
      used to generate individual and group brain activation maps. For input region
      determination, two intrinsic connectivity models comprising bilateral HG and STG
      were constructed using dynamic causal modelling (DCM). The models were estimated
      and inferred using DCM while Bayesian Model Selection (BMS) for group studies was
      used for model comparison and selection. Based on the winning model, six linear
      and six non-linear causal models were derived and were again estimated, inferred,
      and compared to obtain a model that best represents the effective connectivity
      between HG and the STG, balancing accuracy and complexity. RESULTS: Group results
      indicated significant asymmetrical activation (p(uncorr) < 0.001) in bilateral HG
      and STG. Model comparison results showed strong evidence of STG as the input
      centre. The winning model is preferred by 6 out of 10 participants. The results
      were supported by BMS results for group studies with the expected posterior
      probability, r = 0.7830 and exceedance probability, phi = 0.9823. One-sample t
      tests performed on connection values obtained from the winning model indicated
      that the valid connections for the winning model are the unidirectional parallel
      connections from STG to bilateral HG (p < 0.05). Subsequent model comparison
      between linear and non-linear models using BMS prefers non-linear connection (r =
      0.9160, phi = 1.000) from which the connectivity between STG and the ipsi- and
      contralateral HG is gated by the activity in STG itself. CONCLUSION: We are able
      to demonstrate that the effective connectivity between HG and STG while listening
      to white noise for the respective participants can be explained by a non-linear
      dynamic causal model with the activity in STG influencing the STG-HG connectivity
      non-linearly.

PMID- 22970071
TI  - Musculoskeletal health professional use of internet resources for personal and
      patient education: results from an online national survey.
AB  - OBJECTIVES: To study the current practice of computer use in musculoskeletal
      health professionals for their education and that of their patients. METHODS: A
      survey questionnaire, designed by a working group including representatives from
      Arthritis Research UK and the British Society for Rheumatology, was made
      available on surveymonkey.com and the link distributed by email. RESULTS: 190
      health professionals responded. Rheumatology professionals made up two thirds of
      the participants. The modal age group of responders was under 40 years (37%). 97%
      had spent some educational time on a computer. Females were younger and spent
      more time using the computer for education purposes. The preferred learning
      modality was interactive online content (71%). The most common methods of
      educating patients were the Consultant and Specialist nurse while the web is used
      by 40% of the health professionals. The most common barrier to education was
      'Insufficient resources for education groups'. Rheumatologists were more likely
      to log Continuous Professional Development (CPD) online, complete online modules
      and have mandatory training online. UpToDate and Arthritis Research UK were the
      highest rated websites for health professional and patient education
      respectively. CONCLUSIONS: This is the first national survey of E-learning in the
      musculoskeletal health profession, with a large proportion of Rheumatologists.
      Almost all use computer based learning. Use of the internet for patient education
      is low. Highly rated educational websites are available for both professionals
      and patients.

PMID- 22970102
TI  - Open field release of genetically engineered sterile male Aedes aegypti in
      Malaysia.
AB  - BACKGROUND: Dengue is the most important mosquito-borne viral disease. In the
      absence of specific drugs or vaccines, control focuses on suppressing the
      principal mosquito vector, Aedes aegypti, yet current methods have not proven
      adequate to control the disease. New methods are therefore urgently needed, for
      example genetics-based sterile-male-release methods. However, this requires that
      lab-reared, modified mosquitoes be able to survive and disperse adequately in the
      field. METHODOLOGY/PRINCIPAL FINDINGS: Adult male mosquitoes were released into
      an uninhabited forested area of Pahang, Malaysia. Their survival and dispersal
      was assessed by use of a network of traps. Two strains were used, an engineered
      'genetically sterile' (OX513A) and a wild-type laboratory strain, to give both
      absolute and relative data about the performance of the modified mosquitoes. The
      two strains had similar maximum dispersal distances (220 m), but mean distance
      travelled of the OX513A strain was lower (52 vs. 100 m). Life expectancy was
      similar (2.0 vs. 2.2 days). Recapture rates were high for both strains, possibly
      because of the uninhabited nature of the site. CONCLUSIONS/SIGNIFICANCE: After
      extensive contained studies and regulatory scrutiny, a field release of
      engineered mosquitoes was safely and successfully conducted in Malaysia. The
      engineered strain showed similar field longevity to an unmodified counterpart,
      though in this setting dispersal was reduced relative to the unmodified strain.
      These data are encouraging for the future testing and implementation of genetic
      control strategies and will help guide future field use of this and other
      engineered strains.

PMID- 22970103
TI  - Primary human airway epithelial cell-dependent inhibition of human lung mast cell
      degranulation.
AB  - INTRODUCTION: Chronic mast cell activation is a characteristic feature of asthma.
      BEAS-2B human airway epithelial cells (AEC) profoundly inhibit both constitutive
      and IgE-dependent human lung mast cell (HLMC) histamine release. The aim of this
      study was to examine the regulation of HLMC degranulation by primary AEC from
      healthy and asthmatic subjects, and investigate further the inhibitory mechanism.
      METHODS: HLMC were co-cultured with both BEAS-2B and primary AEC grown as
      monolayers or air-liquid interface (ALI) cultures. RESULTS: Both constitutive and
      IgE-dependent HLMC histamine release were attenuated by BEAS-2B, primary AEC
      monolayers and ALI cultures. This occurred in the absence of HLMC-AEC contact
      indicating the presence of a soluble factor. Unlike healthy ALI AEC, asthmatic
      ALI-AEC did not significantly reduce constitutive histamine release. AEC
      inhibitory activity was transferable in primary AEC monolayer supernatant, but
      less active than with Transwell co-culture, suggesting that the inhibitory factor
      was labile. The AEC inhibitory effects were attenuated by both AEC wounding and
      pertussis toxin, indicating the involvement of a G(0)/G(i) receptor coupled
      mechanism. Solid phase extraction of lipids (<10 kDa) removed the AEC inhibitory
      activity. The lipid derivatives resolving D1 and D2 and lipoxin A(4) attenuated
      HLMC histamine release in a dose-dependent fashion but were not detectable in co
      culture supernatants. CONCLUSIONS: Primary AEC suppress HLMC constitutive and IgE
      dependent histamine secretion through the release of a soluble, labile lipid
      mediator(s) that signals through the G(0)/G(i) receptor coupled mechanism.
      Manipulation of this interaction may have a significant therapeutic role in
      asthma.

PMID- 22970104
TI  - Pitfalls of establishing DNA barcoding systems in protists: the cryptophyceae as
      a test case.
AB  - A DNA barcode is a preferrably short and highly variable region of DNA supposed
      to facilitate a rapid identification of species. In many protistan lineages, a
      lack of species-specific morphological characters hampers an identification of
      species by light or electron microscopy, and difficulties to perform mating
      experiments in laboratory cultures also do not allow for an identification of
      biological species. Thus, testing candidate barcode markers as well as
      establishment of accurately working species identification systems are more
      challenging than in multicellular organisms. In cryptic species complexes the
      performance of a potential barcode marker can not be monitored using
      morphological characters as a feedback, but an inappropriate choice of DNA region
      may result in artifactual species trees for several reasons. Therefore a priori
      knowledge of the systematics of a group is required. In addition to
      identification of known species, methods for an automatic delimitation of species
      with DNA barcodes have been proposed. The Cryptophyceae provide a mixture of
      systematically well characterized as well as badly characterized groups and are
      used in this study to test the suitability of some of the methods for protists.
      As species identification method the performance of blast in searches against
      badly to well-sampled reference databases has been tested with COI-5P and 5'
      partial LSU rDNA (domains A to D of the nuclear LSU rRNA gene). In addition the
      performance of two different methods for automatic species delimitation, fixed
      thresholds of genetic divergence and the general mixed Yule-coalescent model
      (GMYC), have been examined. The study demonstrates some pitfalls of barcoding
      methods that have to be taken care of. Also a best-practice approach towards
      establishing a DNA barcode system in protists is proposed.

PMID- 22970106
TI  - Vigabatrin-induced retinal toxicity is partially mediated by signaling in rod and
      cone photoreceptors.
AB  - Vigabatrin (VGB) is a commonly prescribed antiepileptic drug designed to inhibit
      GABA-transaminase, effectively halting seizures. Unfortunately, VGB treatment is
      also associated with the highest frequencies of peripheral visual field
      constriction of any of the antiepileptic drugs and the mechanisms that lead to
      these visual field defects are uncertain. Recent studies have demonstrated light
      exposure exacerbates vigabatrin-induced retinal toxicity. We further assessed
      this relationship by examining the effects of vigabatrin treatment on the retinal
      structures of mice with genetically altered photoreception. In keeping with
      previous studies, we detected increased toxicity in mice exposed to continuous
      light. To study whether cone or rod photoreceptor function was involved in the
      pathway to toxicity, we tested mice with mutations in the cone-specific Gnat2 or
      rod-specific Pde6g genes, and found the mutations significantly reduced VGB
      toxicity. Our results confirm light is a significant enhancer of vigabatrin
      toxicity and that a portion of this is mediated, directly or indirectly, by
      phototransduction signaling in rod and cone photoreceptors.

PMID- 22970107
TI  - The meaning of adherence when behavioral risk patterns vary: obscured use- and
      method-effectiveness in HIV-prevention trials.
AB  - BACKGROUND: Recently promising trials of innovative biomedical approaches to
      prevent HIV transmission have been reported. Participants' non-adherence to the
      prevention methods complicates the analyses and interpretation of trial results.
      The influence of variable sexual behaviors within and between participants of
      trials further obscures matters. Current methodological and statistical
      approaches in HIV-prevention studies, as well as ongoing debates on contradictory
      trial results, may fail to accurately address these topics. METHODOLOGY/PRINCIPAL
      FINDINGS: Through developing a cumulative probability model of infection within
      HIV prevention trials, we demonstrate how adherence and sexual behavior patterns
      impact the overall estimate of effectiveness, the effectiveness of prevention
      methods as a function of adherence, and conclusions about methods' true
      effectiveness. Applying the model to summary-level data from the CAPRISA trial,
      we observe markedly different values for the true method effectiveness of the
      microbicide, and show that if the gel would have been tested among women with
      slightly different sexual behavior patterns, conclusions might well have been
      that the gel is not effective. CONCLUSIONS/SIGNIFICANCE: Relative risk and
      adherence analyses in HIV prevention trials overlook the complex interplay
      between adherence and sexual behavior patterns. Consequently, they may not
      provide accurate estimates of use- and method-effectiveness. Moreover, trial
      conclusions are contingent upon the predominant sexual behavior pattern of
      participants and cannot be directly generalized to other contexts. We recommend
      researchers to (re)examine their data and use the cumulative probability model to
      estimate the true method effectiveness, which might contribute to resolving
      current questions about contradictory trial results. Moreover, we suggest taking
      into account the issues raised in the design of future trials and in population
      models estimating the impact of large-scale dissemination of prevention methods.
      Comprehension of the topics described will help readers to better interpret
      (apparently contradictory) trial outcomes.

PMID- 22970105
TI  - T cell activation markers and African mitochondrial DNA haplogroups among non
      Hispanic black participants in AIDS clinical trials group study 384.
AB  - INTRODUCTION: Mitochondrial function influences T cell dynamics and is affected
      by mitochondrial DNA (mtDNA) variation. We previously reported an association
      between African mtDNA haplogroup L2 and less robust CD4 cell recovery on
      antiretroviral therapy (ART) in non-Hispanic black ACTG 384 subjects. We explored
      whether additional T cell parameters in this cohort differed by mtDNA haplogroup.
      METHODS: ACTG 384 randomized ART-naive subjects to two different nucleoside
      regimens with efavirenz, nelfinavir, or both. CD4 and CD8 memory and activation
      markers were available at baseline and week 48 on most subjects. mtDNA sequencing
      was performed on whole blood DNA, and haplogroups were determined. We studied non
      Hispanic black subjects with HIV RNA <400 copies/mL at week 48. Analyses included
      Wilcoxon ranksum test and linear regression. RESULTS: Data from 104 subjects were
      included. Major African mtDNA haplogroups included L1 (N=25), L2 (N=31), and L3
      (N=32). Baseline age, HIV RNA, and CD4 cells did not differ between L2 and non-L2
      haplogroups. Compared to non-L2 haplogroups, L2 subjects had lower baseline
      activated CD4 cells (median 12% vs. 17%; p=0.03) and tended toward lower
      activated CD8 cells (41% vs. 47%; p=0.06). At 48 weeks of ART, L2 subjects had
      smaller decreases in activated CD4 cells (-4% vs. -11%; p=0.01), and smaller CD4
      cell increases (+95 vs. +178; p=0.002). In models adjusting for baseline age, CD4
      cells, HIV RNA, and naive-to-memory CD4 cell ratio, haplogroup L2 was associated
      with lower baseline (p=0.04) and 48-week change in (p=0.01) activated CD4 cells.
      CONCLUSIONS: Among ART-naive non-Hispanic blacks, mtDNA haplogroup L2 was
      associated with baseline and 48-week change in T cell activation, and poorer CD4
      cell recovery. These data suggest mtDNA variation may influence CD4 T cell
      dynamics by modulating T cell activation. Further study is needed to replicate
      these associations and identify mechanisms.

PMID- 22970110
TI  - Retraction: Transgenic biofortification of the starchy staple cassava (Manihot
      esculenta) generates a novel sink for protein.

PMID- 22970109
TI  - Results of an action-research on epilepsy in rural Mali.
AB  - PURPOSE: To evaluate the RARE (Reseau Action-Recherche sur l'Epilepsie) program,
      a model of managing and treating people with epilepsy (PWE) at a primary health
      care level in rural areas of Mali, we assessed treatment efficacy and compliance
      of patients who underwent the first year follow-up. METHODS: A network of rural
      general practitioners (GPs) settled in six rural districts of the regions of
      Koulikoro, Segou and Sikasso, was involved in the diagnosis, evaluation and
      monitoring of all the identified PWE and in the distribution of phenobarbital
      (PB). All the participants were included in a prospective database and followed
      up by GPs at 4 months intervals during the first year. Seizure frequency,
      treatment doses and appearance of adverse events (AEs) were systematically
      recorded. Efficacy was evaluated in terms of reduction of seizures frequency
      while noncompliance in terms of time to study withdrawal for any cause. KEY
      FINDINGS: 596 patients treated with PB were included in the analysis. Of these,
      74.0% completed the first year follow-up. At the final visit, 59.6% were seizure
      free: 31.0% for 12 months, 10.2% for 8 months and 18.4% for 4 months. Adults and
      patients with convulsive seizures were the most drug-resistant (p<0.002). Few AEs
      were recorded. The multivariate analysis showed that being a woman, presenting
      convulsive seizures, having more than 5 seizures/month and had never be treated
      were predictors of withdrawal (p <= 0.05) at 12 months. SIGNIFICANCE: This study
      showed a good response and compliance to the treatment and allowed the
      identification of some factors associated with failure of management in a setting
      very near to clinical practice. Awareness campaigns are needed to assure a
      broader accessibility to treatment and to improve the compliance and continuity
      with treatment programs.

PMID- 22970108
TI  - Stromal-to-epithelial transition during postpartum endometrial regeneration.
AB  - Endometrium is the inner lining of the uterus which is composed of epithelial and
      stromal tissue compartments enclosed by the two smooth muscle layers of the
      myometrium. In women, much of the endometrium is shed and regenerated each month
      during the menstrual cycle. Endometrial regeneration also occurs after
      parturition. The cellular mechanisms that regulate endometrial regeneration are
      still poorly understood. Using genetic fate-mapping in the mouse, we found that
      the epithelial compartment of the endometrium maintains its epithelial identity
      during the estrous cycle and postpartum regeneration. However, whereas the
      stromal compartment maintains its identity during homeostatic cycling, after
      parturition a subset of stromal cells differentiates into epithelium that is
      subsequently maintained. These findings identify potential progenitor cells
      within the endometrial stromal compartment that produce long-term epithelial
      tissue during postpartum endometrial regeneration.

PMID- 22970111
TI  - The enzymatic and metabolic capabilities of early life.
AB  - We introduce the concept of metaconsensus and employ it to make high confidence
      predictions of early enzyme functions and the metabolic properties that they may
      have produced. Several independent studies have used comparative bioinformatics
      methods to identify taxonomically broad features of genomic sequence data,
      protein structure data, and metabolic pathway data in order to predict
      physiological features that were present in early, ancestral life forms. But all
      such methods carry with them some level of technical bias. Here, we cross
      reference the results of these previous studies to determine enzyme functions
      predicted to be ancient by multiple methods. We survey modern metabolic pathways
      to identify those that maintain the highest frequency of metaconsensus enzymes.
      Using the full set of modern reactions catalyzed by these metaconsensus enzyme
      functions, we reconstruct a representative metabolic network that may reflect the
      core metabolism of early life forms. Our results show that ten enzyme functions,
      four hydrolases, three transferases, one oxidoreductase, one lyase, and one
      ligase, are determined by metaconsensus to be present at least as late as the
      last universal common ancestor. Subnetworks within central metabolic processes
      related to sugar and starch metabolism, amino acid biosynthesis, phospholipid
      metabolism, and CoA biosynthesis, have high frequencies of these enzyme
      functions. We demonstrate that a large metabolic network can be generated from
      this small number of enzyme functions.

PMID- 22970112
TI  - Microbial diversity and potential pathogens in ornamental fish aquarium water.
AB  - Ornamental fishes are among the most popular and fastest growing categories of
      pets in the United States (U.S.). The global scope and scale of the ornamental
      fish trade and growing popularity of pet fish in the U.S. are strong indicators
      of the myriad economic and social benefits the pet industry provides. Relatively
      little is known about the microbial communities associated with these ornamental
      fishes or the aquarium water in which they are transported and housed. Using
      conventional molecular approaches and next generation high-throughput amplicon
      sequencing of 16S ribosomal RNA gene hypervariable regions, we characterized the
      bacterial community of aquarium water containing common goldfish (Carassius
      auratus) and Chinese algae eaters (Gyrinocheilus aymonieri) purchased from seven
      pet/aquarium shops in Rhode Island and identified the presence of potential
      pathogens. Our survey identified a total of 30 phyla, the most common being
      Proteobacteria (52%), Bacteroidetes (18%) and Planctomycetes (6%), with the top
      four phyla representing >80% of all sequences. Sequences from our water samples
      were most closely related to eleven bacterial species that have the potential to
      cause disease in fishes, humans and other species: Coxiella burnetii,
      Flavobacterium columnare, Legionella birminghamensis, L. pneumophila, Vibrio
      cholerae, V. mimicus. V. vulnificus, Aeromonas schubertii, A. veronii, A.
      hydrophila and Plesiomonas shigelloides. Our results, combined with evidence from
      the literature, suggest aquarium tank water harboring ornamental fish are an
      understudied source for novel microbial communities and pathogens that pose
      potential risks to the pet industry, fishes in trade, humans and other species.

PMID- 22970113
TI  - Evaluation of OPEN zinc finger nucleases for direct gene targeting of the ROSA26
      locus in mouse embryos.
AB  - Zinc finger nucleases (ZFNs) enable precise genome modification in a variety of
      organisms and cell types. Commercial ZFNs were reported to enhance gene targeting
      directly in mouse zygotes, whereas similar approaches using publicly available
      resources have not yet been described. Here we report precise targeted
      mutagenesis of the mouse genome using Oligomerized Pool Engineering (OPEN) ZFNs.
      OPEN ZFN can be constructed using publicly available resources and therefore
      provide an attractive alternative for academic researchers. Two ZFN pairs
      specific to the mouse genomic locus gt(ROSA26)Sor were generated by OPEN
      selections and used for gene disruption and homology-mediated gene replacement in
      single cell mouse embryos. One specific ZFN pair facilitated non-homologous end
      joining (NHEJ)-mediated gene disruption when expressed in mouse zygotes. We also
      observed a single homologous recombination (HR)-driven gene replacement event
      when this ZFN pair was co-injected with a targeting vector. Our experiments
      demonstrate the feasibility of achieving both gene ablation through NHEJ and gene
      replacement by HR by using the OPEN ZFN technology directly in mouse zygotes.

PMID- 22970114
TI  - A public HTLV-1 molecular epidemiology database for sequence management and data
      mining.
AB  - BACKGROUND: It is estimated that 15 to 20 million people are infected with the
      human T-cell lymphotropic virus type 1 (HTLV-1). At present, there are more than
      2,000 unique HTLV-1 isolate sequences published. A central database to aggregate
      sequence information from a range of epidemiological aspects including HTLV-1
      infections, pathogenesis, origins, and evolutionary dynamics would be useful to
      scientists and physicians worldwide. Described here, we have developed a database
      that collects and annotates sequence data and can be accessed through a user
      friendly search interface. The HTLV-1 Molecular Epidemiology Database website is
      available at http://htlv1db.bahia.fiocruz.br/. METHODOLOGY/PRINCIPAL FINDINGS:
      All data was obtained from publications available at GenBank or through contact
      with the authors. The database was developed using Apache Webserver 2.1.6 and
      SGBD MySQL. The webpage interfaces were developed in HTML and sever-side
      scripting written in PHP. The HTLV-1 Molecular Epidemiology Database is hosted on
      the Goncalo Moniz/FIOCRUZ Research Center server. There are currently 2,457
      registered sequences with 2,024 (82.37%) of those sequences representing unique
      isolates. Of these sequences, 803 (39.67%) contain information about clinical
      status (TSP/HAM, 17.19%; ATL, 7.41%; asymptomatic, 12.89%; other diseases, 2.17%;
      and no information, 60.32%). Further, 7.26% of sequences contain information on
      patient gender while 5.23% of sequences provide the age of the patient.
      CONCLUSIONS/SIGNIFICANCE: The HTLV-1 Molecular Epidemiology Database retrieves
      and stores annotated HTLV-1 proviral sequences from clinical, epidemiological,
      and geographical studies. The collected sequences and related information are now
      accessible on a publically available and user-friendly website. This open-access
      database will support clinical research and vaccine development related to viral
      genotype.

PMID- 22970116
TI  - Improved minimum cost and maximum power two stage genome-wide association study
      designs.
AB  - In a two stage genome-wide association study (2S-GWAS), a sample of cases and
      controls is allocated into two groups, and genetic markers are analyzed
      sequentially with respect to these groups. For such studies, experimental design
      considerations have primarily focused on minimizing study cost as a function of
      the allocation of cases and controls to stages, subject to a constraint on the
      power to detect an associated marker. However, most treatments of this problem
      implicitly restrict the set of feasible designs to only those that allocate the
      same proportions of cases and controls to each stage. In this paper, we
      demonstrate that removing this restriction can improve the cost advantages
      demonstrated by previous 2S-GWAS designs by up to 40%. Additionally, we consider
      designs that maximize study power with respect to a cost constraint, and show
      that recalculated power maximizing designs can recover a substantial amount of
      the planned study power that might otherwise be lost if study funding is reduced.
      We provide open source software for calculating cost minimizing or power
      maximizing 2S-GWAS designs.

PMID- 22970115
TI  - The goblet cell is the cellular source of the anti-microbial angiogenin 4 in the
      large intestine post Trichuris muris infection.
AB  - BACKGROUND: Mouse angiogenin 4 (Ang4) has previously been described as a Paneth
      cell-derived antimicrobial peptide important in epithelial host defence in the
      small intestine. However, a source for Ang4 in the large intestine, which is
      devoid of Paneth cells, has not been defined. METHODOLOGY/PRINCIPAL FINDINGS:
      Analysis was performed on Ang4 expression in colonic tissue by qPCR and
      immunohistochemistry following infection with the large intestine dwelling
      helminth parasite Trichuris muris. This demonstrated an increase in expression of
      the peptide following infection of resistant BALB/c mice. Further, histological
      analysis of colonic tissue revealed the cellular source of this Ang4 to be goblet
      cells. To elucidate the mechanism of Ang4 expression immunohistochemistry and
      qPCR for Ang4 was performed on colonic tissue from T. muris infected mouse
      mutants. Experiments comparing C3H/HeN and C3H/HeJ mice, which have a natural
      inactivating mutation of TLR4, revealed that Ang4 expression is TLR4 independent.
      Subsequent experiments with IL-13 and IL-4 receptor alpha deficient mice
      demonstrated that goblet cell expression of Ang4 is controlled either directly or
      indirectly by IL-13. CONCLUSIONS: The cellular source of mouse Ang4 in the colon
      following T. muris infection is the goblet cell and expression is under the
      control of IL-13.

PMID- 22970117
TI  - Identification of elongation factor G as the conserved cellular target of argyrin
      B.
AB  - Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides
      with antibacterial and antitumor activity. Here, we identify elongation factor G
      (EF-G) as the cellular target of argyrin B in bacteria, via resistant mutant
      selection and whole genome sequencing, biophysical binding studies and
      crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from
      the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein
      synthesis inhibition. In eukaryotic cells, argyrin B was found to target
      mitochondrial elongation factor G1 (EF-G1), the closest homologue of bacterial EF
      G. By blocking mitochondrial translation, argyrin B depletes electron transport
      components and inhibits the growth of yeast and tumor cells. Further supporting
      direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1
      L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary,
      we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the
      evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and
      mitochondrial translation in yeast and mammalian cells.

PMID- 22970118
TI  - Assessing bacterial populations in the lung by replicate analysis of samples from
      the upper and lower respiratory tracts.
AB  - Microbes of the human respiratory tract are important in health and disease, but
      accurate sampling of the lung presents challenges. Lung microbes are commonly
      sampled by bronchoscopy, but to acquire samples the bronchoscope must pass
      through the upper respiratory tract, which is rich in microbes. Here we present
      methods to identify authentic lung microbiota in bronchoalveolar lavage (BAL)
      fluid that contains substantial oropharyngeal admixture. We studied clinical BAL
      samples from six selected subjects with potential heavy lung colonization. A
      single sample of BAL fluid was obtained from each subject along with
      contemporaneous oral wash (OW) to sample the oropharynx, and then DNA was
      extracted from three separate aliquots of each. Bacterial 16S rDNA sequences were
      amplified and products analyzed by 454 pyrosequencing. By comparing replicates,
      we were able to specify the depth of sequencing needed to reach a 95% chance of
      identifying a bacterial lineage of a given proportion--for example, at a depth of
      5,000 tags, OTUs of proportion 0.3% or greater would be called with 95%
      confidence. We next constructed a single-sided outlier test that allowed lung
      enriched organisms to be quantified against a background of oropharyngeal
      admixture, and assessed improvements available with replicate sequence analysis.
      This allowed identification of lineages enriched in lung in some BAL specimens.
      Finally, using samples from healthy volunteers collected at multiple sites in the
      upper respiratory tract, we show that OW provides a reasonable but not perfect
      surrogate for bacteria carried into to the lung by a bronchoscope. These methods
      allow identification of microbes that can replicate in the lung despite the
      background due to oropharyngeal microbes derived from aspiration and
      bronchoscopic carry-over.

PMID- 22970119
TI  - Corrections in grasp posture in response to modifications of action goals.
AB  - There is ample evidence that people plan their movements to ensure comfortable
      final grasp postures at the end of a movement. The end-state comfort effect has
      been found to be a robust constraint during unimanual movements, and leads to the
      inference that goal-postures are represented and planned prior to movement
      initiation. The purpose of this study was to examine whether individuals make
      appropriate corrections to ensure comfortable final goal postures when faced with
      an unexpected change in action goal. Participants reached for a horizontal
      cylinder and placed the left or right end of the object into the target disk. As
      soon as the participant began to move, a secondary stimuli was triggered, which
      indicated whether the intended action goal had changed or not. Confirming
      previous research, participants selected initial grasp postures that ensured end
      state comfort during non-perturbed trials. In addition, participants made
      appropriate on-line corrections to their reach-to-grasp movements to ensure end
      state comfort during perturbed trials. Corrections in grasp posture occurred
      early or late in the reach-to-grasp phase. The results indicate that individuals
      plan their movements to afford comfort at the end of the movement, and that grasp
      posture planning is controlled via both feedforward and feedback mechanisms.

PMID- 22970120
TI  - Male out-migration: a factor for the spread of HIV infection among married men
      and women in rural India.
AB  - INTRODUCTION: Thus far, the reasons for increasing HIV prevalence in northern and
      eastern Indian states are unknown. We investigated the role of male out-migration
      in the spread of human immunodeficiency virus (HIV) infection through a case
      control study in rural India. METHODS: Currently married men and women were
      recruited from HIV testing and treatment centers across seven selected districts
      with high rates of male out-migration in eastern and northern India in 2010 using
      a case-control study design. Case subjects (men: 595, women: 609) were people who
      tested HIV seropositive and control subjects (men: 611, women: 600) were those
      tested HIV seronegative. For each gender, we obtained adjusted odds ratios (AORs)
      and population attributable risks (PARs) for migration, and behavioral factors.
      RESULTS: For men, the prevalence of HIV was significantly higher among those with
      a migration history (AOR, 4.4); for women, the prevalence of HIV was higher among
      those with migrant husbands (AOR, 2.3). For both genders, the returned male
      migration (men: AOR, 3.7; women: AOR, 28) was significantly associated with
      higher prevalence of HIV infection. The PAR associated with male migration was
      higher for men (54.5%-68.6%) than for women (32.7%-56.9%) across the study areas.
      DISCUSSION: Male out-migration is the most important risk factor influencing the
      spread of HIV infection in rural areas with high out-migration rates, thereby
      emphasizing the need for interventions, particularly, for returned migrants and
      spouses of those migrants.

PMID- 22970121
TI  - Serum 25(OH)D is a 2-year predictor of all-cause mortality, cardiac death and
      sudden cardiac death in chest pain patients from Northern Argentina.
AB  - BACKGROUND: Several studies have shown an association between vitamin D
      deficiency and cardiovascular risk. Vitamin D status is assessed by determination
      of 25-hydroxyvitamin D [25(OH)D] in serum. METHODS: We assessed the prognostic
      utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary
      syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including
      all-cause mortality, cardiac death and sudden cardiac death were analyzed in
      quartiles of 25(OH)D, applying univariate and multivariate analysis. RESULTS:
      There were statistically significant changes in seasonal 25(OH)D levels. At
      follow-up, 119 patients had died. The mean 25(OH)D levels were significantly
      lower among patients dying than in long-term survivors, both in the total
      population and in patients with a troponin T (TnT) release (n = 388). When
      comparing 25(OH)D in the highest quartile to the lowest quartile in a
      multivariable Cox regression model for all-cause mortality, the hazard ratio (HR)
      for cardiac death and sudden cardiac death in the total population was 0.37 (95%
      CI, 0.19-0.73), p = 0.004, 0.23 (95% CI, 0.08-0.67), p = 0.007, and 0.32 (95% CI,
      0.11-0.94), p = 0.038, respectively. In patients with TnT release, the respective
      HR was 0.24 (95% CI, 0.10-0.54), p = 0.001, 0.18 (95% CI, 0.05-0.60), p = 0.006
      and 0.25 (95% CI, 0.07-0.89), p = 0.033. 25(OH)D had no prognostic value in
      patients with no TnT release. CONCLUSION: Vitamin D was shown to be a useful
      biomarker for prediction of mortality when obtained at admission in chest pain
      patients with suspected ACS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01377402.

PMID- 22970122
TI  - Assessing coral reefs on a Pacific-wide scale using the microbialization score.
AB  - The majority of the world's coral reefs are in various stages of decline. While a
      suite of disturbances (overfishing, eutrophication, and global climate change)
      have been identified, the mechanism(s) of reef system decline remain elusive.
      Increased microbial and viral loading with higher percentages of opportunistic
      and specific microbial pathogens have been identified as potentially unifying
      features of coral reefs in decline. Due to their relative size and high per cell
      activity, a small change in microbial biomass may signal a large reallocation of
      available energy in an ecosystem; that is the microbialization of the coral reef.
      Our hypothesis was that human activities alter the energy budget of the reef
      system, specifically by altering the allocation of metabolic energy between
      microbes and macrobes. To determine if this is occurring on a regional scale, we
      calculated the basal metabolic rates for the fish and microbial communities at 99
      sites on twenty-nine coral islands throughout the Pacific Ocean using previously
      established scaling relationships. From these metabolic rate predictions, we
      derived a new metric for assessing and comparing reef health called the
      microbialization score. The microbialization score represents the percentage of
      the combined fish and microbial predicted metabolic rate that is microbial. Our
      results demonstrate a strong positive correlation between reef microbialization
      scores and human impact. In contrast, microbialization scores did not
      significantly correlate with ocean net primary production, local chla
      concentrations, or the combined metabolic rate of the fish and microbial
      communities. These findings support the hypothesis that human activities are
      shifting energy to the microbes, at the expense of the macrobes. Regardless of
      oceanographic context, the microbialization score is a powerful metric for
      assessing the level of human impact a reef system is experiencing.

PMID- 22970123
TI  - DNA barcoding as an effective tool in improving a digital plant identification
      system: a case study for the area of Mt. Valerio, Trieste (NE Italy).
AB  - BACKGROUND: Identification keys are decision trees which require the observation
      of one or more morphological characters of an organism at each step of the
      process. While modern digital keys can overcome several constraints of classical
      paper-printed keys, their performance is not error-free. Moreover, identification
      cannot be always achieved when a specimen lacks some morphological features (i.e.
      because of season, incomplete development or miss-collecting). DNA barcoding was
      proven to have great potential in plant identification, while it can be
      ineffective with some closely related taxa, in which the relatively brief
      evolutionary distance did not produce differences in the core-barcode sequences.
      METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we investigated how the DNA
      barcoding can support the modern digital approaches to the identification of
      organisms, using as a case study a local flora, that of Mt. Valerio, a small hill
      near the centre of Trieste (NE Italy). The core barcode markers (plastidial rbcL
      and matK), plus the additional trnH-psbA region, were used to identify vascular
      plants specimens. The usefulness of DNA barcoding data in enhancing the
      performance of a digital identification key was tested on three independent
      simulated scenarios. CONCLUSIONS/SIGNIFICANCE: Our results show that the core
      barcode markers univocally identify most species of our local flora (96%). The
      trnH-psbA data improve the discriminating power of DNA barcoding among closely
      related plant taxa. In the multiparametric digital key, DNA barcoding data
      improves the identification success rate; in our simulation, DNA data overcame
      the absence of some morphological features, reaching a correct identification for
      100% of the species. FRIDA, the software used to generate the digital key, has
      the potential to combine different data sources: we propose to use this feature
      to include molecular data as well, creating an integrated identification system
      for plant biodiversity surveys.

PMID- 22970124
TI  - Bayesian selection of Markov models for symbol sequences: application to
      microsaccadic eye movements.
AB  - Complex biological dynamics often generate sequences of discrete events which can
      be described as a Markov process. The order of the underlying Markovian
      stochastic process is fundamental for characterizing statistical dependencies
      within sequences. As an example for this class of biological systems, we
      investigate the Markov order of sequences of microsaccadic eye movements from
      human observers. We calculate the integrated likelihood of a given sequence for
      various orders of the Markov process and use this in a Bayesian framework for
      statistical inference on the Markov order. Our analysis shows that data from most
      participants are best explained by a first-order Markov process. This is
      compatible with recent findings of a statistical coupling of subsequent
      microsaccade orientations. Our method might prove to be useful for a broad class
      of biological systems.

PMID- 22970125
TI  - Improving DTI tractography by including diagonal tract propagation.
AB  - Tractography algorithms have been developed to reconstruct likely WM pathways in
      the brain from diffusion tensor imaging (DTI) data. In this study, an elegant and
      simple means for improving existing tractography algorithms is proposed by
      allowing tracts to propagate through diagonal trajectories between voxels,
      instead of only rectilinearly to their facewise neighbors. A series of tests
      (using both real and simulated data sets) are utilized to show several benefits
      of this new approach. First, the inclusion of diagonal tract propagation
      decreases the dependence of an algorithm on the arbitrary orientation of
      coordinate axes and therefore reduces numerical errors associated with that bias
      (which are also demonstrated here). Moreover, both quantitatively and
      qualitatively, including diagonals decreases overall noise sensitivity of results
      and leads to significantly greater efficiency in scanning protocols; that is, the
      obtained tracts converge much more quickly (i.e., in a smaller amount of scanning
      time) to those of data sets with high SNR and spatial resolution. Importantly,
      the inclusion of diagonal propagation adds essentially no appreciable time of
      calculation or computational costs to standard methods. This study focuses on the
      widely-used streamline tracking method, FACT (fiber assessment by continuous
      tracking), and the modified method is termed "FACTID" (FACT including diagonals).

PMID- 22970126
TI  - 'Natural experiment' demonstrates top-down control of spiders by birds on a
      landscape level.
AB  - The combination of small-scale manipulative experiments and large-scale natural
      experiments provides a powerful approach for demonstrating the importance of top
      down trophic control on the ecosystem scale. The most compelling natural
      experiments have come from studies examining the landscape-scale loss of apex
      predators like sea otters, wolves, fish and land crabs. Birds are dominant apex
      predators in terrestrial systems around the world, yet all studies on their role
      as predators have come from small-scale experiments; the top-down impact of bird
      loss on their arthropod prey has yet to be examined at a landscape scale. Here,
      we use a unique natural experiment, the extirpation of insectivorous birds from
      nearly all forests on the island of Guam by the invasive brown tree snake, to
      produce the first assessment of the impacts of bird loss on their prey. We
      focused on spiders because experimental studies showed a consistent top-down
      effect of birds on spiders. We conducted spider web surveys in native forest on
      Guam and three nearby islands with healthy bird populations. Spider web densities
      on the island of Guam were 40 times greater than densities on islands with birds
      during the wet season, and 2.3 times greater during the dry season. These results
      confirm the general trend from manipulative experiments conducted in other
      systems however, the effect size was much greater in this natural experiment than
      in most manipulative experiments. In addition, bird loss appears to have removed
      the seasonality of spider webs and led to larger webs in at least one spider
      species in the forests of Guam than on nearby islands with birds. We discuss
      several possible mechanisms for the observed changes. Overall, our results
      suggest that effect sizes from smaller-scale experimental studies may
      significantly underestimate the impact of bird loss on spider density as
      demonstrated by this large-scale natural experiment.

PMID- 22970127
TI  - A fluorescent, genetically-encoded voltage probe capable of resolving action
      potentials.
AB  - There is a pressing need in neuroscience for genetically-encoded, fluorescent
      voltage probes that can be targeted to specific neurons and circuits to allow
      study of neural activity using fluorescent imaging. We created 90 constructs in
      which the voltage sensing portion (S1-S4) of Ciona intestinalis voltage sensitive
      phosphatase (CiVSP) was fused to circularly permuted eGFP. This led to
      ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms) than any
      currently published fluorescent protein-based voltage probe. ElectricPk can
      follow the rise and fall of neuronal action potentials with a modest decrease in
      fluorescence intensity (~0.7% DeltaF/F). The probe has a nearly linear
      fluorescence/membrane potential response to both hyperpolarizing and depolarizing
      steps. This is the first probe based on CiVSP that captures the rapid movements
      of the voltage sensor, suggesting that voltage probes designed with circularly
      permuted fluorescent proteins may have some advantages.

PMID- 22970128
TI  - Competitive abilities in experimental microcosms are accurately predicted by a
      demographic index for R*.
AB  - Resource competition theory predicts that R*, the equilibrium resource amount
      yielding zero growth of a consumer population, should predict species'
      competitive abilities for that resource. This concept has been supported for
      unicellular organisms, but has not been well-tested for metazoans, probably due
      to the difficulty of raising experimental populations to equilibrium and
      measuring population growth rates for species with long or complex life cycles.
      We developed an index (R(index)) of R* based on demography of one insect cohort,
      growing from egg to adult in a non-equilibrium setting, and tested whether
      R(index) yielded accurate predictions of competitive abilities using mosquitoes
      as a model system. We estimated finite rate of increase (lambda') from
      demographic data for cohorts of three mosquito species raised with different
      detritus amounts, and estimated each species' R(index) using nonlinear
      regressions of lambda' vs. initial detritus amount. All three species' R(index)
      differed significantly, and accurately predicted competitive hierarchy of the
      species determined in simultaneous pairwise competition experiments. Our R(index)
      could provide estimates and rigorous statistical comparisons of competitive
      ability for organisms for which typical chemostat methods and equilibrium
      population conditions are impractical.

PMID- 22970130
TI  - Resting state functional connectivity in patients with chronic hallucinations.
AB  - Auditory verbal hallucinations (AVH) are not only among the most common but also
      one of the most distressing symptoms of schizophrenia. Despite elaborate
      research, the underlying brain mechanisms are as yet elusive. Functional MRI
      studies have associated the experience of AVH with activation of bilateral
      language-related areas, in particular the right inferior frontal gyrus (rIFG) and
      the left superior temporal gyrus (lSTG). While these findings helped to
      understand the neural underpinnings of hearing voices, they provide little
      information about possible brain mechanisms that predispose a person to
      experience AVH, i.e. the traits to hallucinate. In this study, we compared
      resting state connectivity between 49 psychotic patients with chronic AVH and 49
      matched controls using the rIFG and the lSTG as seed regions, to identify
      functional brain systems underlying the predisposition to hallucinate. The right
      parahippocampal gyrus showed increased connectivity with the rIFG in patients as
      compared to controls. Reduced connectivity with the rIFG in patients was found
      for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG
      in patients was identified in the left frontal operculum as well as the parietal
      opercular area. Connectivity between the lSTG and the left hippocampus was also
      reduced in patients and showed a negative correlation with the severity of
      hallucinations. Concluding, we found aberrant connectivity between the seed
      regions and medial temporal lobe structures which have a prominent role in memory
      retrieval. Moreover, we found decreased connectivity between language-related
      areas, indicating aberrant integration in this system potentially including
      corollary discharge mechanisms.

PMID- 22970129
TI  - An alternative model for the early peopling of southern South America revealed by
      analyses of three mitochondrial DNA haplogroups.
AB  - After several years of research, there is now a consensus that America was
      populated from Asia through Beringia, probably at the end of the Pleistocene. But
      many details such as the timing, route(s), and origin of the first settlers
      remain uncertain. In the last decade genetic evidence has taken on a major role
      in elucidating the peopling of the Americas. To study the early peopling of South
      America, we sequenced the control region of mitochondrial DNA from 300
      individuals belonging to indigenous populations of Chile and Argentina, and also
      obtained seven complete mitochondrial DNA sequences. We identified two novel
      mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together
      with the recently described D1g sub-haplogroup have locally high frequencies and
      are basically restricted to populations from the extreme south of South America.
      The estimated ages of D1g and B2l, about ~15,000 years BP, together with their
      similar population dynamics and the high haplotype diversity shown by the
      networks, suggests that they probably appeared soon after the arrival of the
      first settlers and agrees with the dating of the earliest archaeological sites in
      South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup,
      D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces
      our hypothesis of the continuity of the current Patagonian populations with the
      initial founders. Our results indicate that the extant native populations
      inhabiting South Chile and Argentina are a group which had a common origin, and
      suggest a population break between the extreme south of South America and the
      more northern part of the continent. Thus the early colonization process was not
      just an expansion from north to south, but also included movements across the
      Andes.

PMID- 22970131
TI  - Breaking tolerance in transgenic mice expressing the human TSH receptor A
      subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.
AB  - Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to
      the thyroid are tolerant of the transgene. In transgenics that express low A
      subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti
      CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks
      tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage
      and antibody spreading to other thyroid proteins. In contrast, no thyroiditis
      develops in Hi-expressor transgenics or wild-type mice. Our present goal was to
      determine if thyroiditis could be induced in Hi-expressor transgenics using a
      more potent immunization protocol: Treg depletion, priming with Complete Freund's
      Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts
      with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type
      mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad
      boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad
      boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were
      resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis
      was associated with the development of antibodies to the mouse TSHR downstream of
      the A-subunit. Unexpectedly, we observed that the effect of bacterial products on
      the immune system is a "double-edged sword". On the one hand, priming with CFA
      (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A
      subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the
      other hand, prior treatment with CFA in the absence of A-subunit protein
      inhibited responses to subsequent immunization with A-sub-Ad. Consequently,
      adjuvant activity arising in vivo after bacterial infections combined with a
      protein autoantigen can break self-tolerance but in the absence of the
      autoantigen, adjuvant activity can inhibit the induction of immunity to
      autoantigens (like the TSHR) displaying strong self-tolerance.

PMID- 22970132
TI  - The impact of escaped farmed Atlantic salmon (Salmo salar L.) on catch statistics
      in Scotland.
AB  - In Scotland and elsewhere, there are concerns that escaped farmed Atlantic salmon
      (Salmo salar L.) may impact on wild salmon stocks. Potential detrimental effects
      could arise through disease spread, competition, or inter-breeding. We
      investigated whether there is evidence of a direct effect of recorded salmon
      escape events on wild stocks in Scotland using anglers' counts of caught salmon
      (classified as wild or farmed) and sea trout (Salmo trutta L.). This tests
      specifically whether documented escape events can be associated with reduced or
      elevated escapes detected in the catch over a five-year time window, after
      accounting for overall variation between areas and years. Alternate model
      frameworks were somewhat inconsistent, however no robust association was found
      between documented escape events and higher proportion of farm-origin salmon in
      anglers' catch, nor with overall catch size. A weak positive correlation was
      found between local escapes and subsequent sea trout catch. This is in the
      opposite direction to what would be expected if salmon escapes negatively
      affected wild fish numbers. Our approach specifically investigated documented
      escape events, contrasting with earlier studies examining potentially wider
      effects of salmon farming on wild catch size. This approach is more conservative,
      but alleviates some potential sources of confounding, which are always of concern
      in observational studies. Successful analysis of anglers' reports of escaped
      farmed salmon requires high data quality, particularly since reports of farmed
      salmon are a relatively rare event in the Scottish data. Therefore, as part of
      our analysis, we reviewed studies of potential sensitivity and specificity of
      determination of farmed origin. Specificity estimates are generally high in the
      literature, making an analysis of the form we have performed feasible.

PMID- 22970133
TI  - Valosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3.
AB  - Alterations in the ubiquitin-proteasome system (UPS) have been reported in
      several neurodegenerative disorders characterized by protein misfolding and
      aggregation, including the polylgutamine diseases. Machado-Joseph disease (MJD)
      or Spinocerebellar Ataxia type 3 is caused by a polyglutamine-encoding CAG
      expansion in the ATXN3 gene, which encodes a 42 kDa deubiquitinating enzyme
      (DUB), ataxin-3. We investigated ataxin-3 deubiquitinating activity and the
      functional relevance of ataxin-3 interactions with two proteins previously
      described to interact with ataxin-3, hHR23A and valosin-containing protein
      (VCP/p97). We confirmed ataxin-3 affinity for both hHR23A and VCP/p97. hHR23A and
      ataxin-3 were shown to co-localize in discrete nuclear foci, while VCP/p97 was
      primarily cytoplasmic. hHR23A and VCP/p97 recombinant proteins were added,
      separately or together, to normal and expanded ataxin-3 in in vitro
      deubiquitination assays to evaluate their influence on ataxin-3 activity. VCP/p97
      was shown to be an activator specifically of wild-type ataxin-3, exhibiting no
      effect on expanded ataxin-3, In contrast, we observed no significant alterations
      in ataxin-3 enzyme kinetics or substrate preference in the presence of hHR23A
      alone or in combination with VCP. Based on our results we propose a model where
      ataxin-3 normally functions with its interactors to specify the cellular fate of
      ubiquitinated proteins.

PMID- 22970134
TI  - Mapping the mechanome of live stem cells using a novel method to measure local
      strain fields in situ at the fluid-cell interface.
AB  - During mesenchymal condensation, the initial step of skeletogenesis, transduction
      of minute mechanical forces to the nucleus is associated with up or down
      regulation of genes, ultimately resulting in formation of the skeletal template
      and appropriate cell lineage commitment. The summation of these biophysical cues
      affects the cell's shape and fate. Here, we predict and measure surface strain,
      in live stem cells, in response to controlled delivery of stresses, providing a
      platform to direct short-term structure--function relationships and long-term
      fate decisions. We measure local strains on stem cell surfaces using fluorescent
      microbeads coated with Concanavalin A. During delivery of controlled mechanical
      stresses, 4-Dimensional (x,y,z,t) displacements of the bound beads are measured
      as surface strains using confocal microscopy and image reconstruction. Similarly,
      micro-particle image velocimetry (MU-piv) is used to track flow fields with
      fluorescent microspheres. The measured flow velocity gradient is used to
      calculate stress imparted by fluid drag at the surface of the cell. We compare
      strain measured on cell surfaces with those predicted computationally using
      parametric estimates of the cell's elastic and shear modulus. Finally, cross
      correlating stress--strain data to measures of gene transcription marking lineage
      commitment enables us to create stress--strain--fate maps, for live stem cells in
      situ. The studies show significant correlations between live stem cell stress-
      strain relationships and lineage commitment. The method presented here provides a
      novel means to probe the live stem cell's mechanome, enabling mechanistic studies
      of the role of mechanics in lineage commitment as it unfolds.

PMID- 22970135
TI  - Re-expression of IGF-II is important for beta cell regeneration in adult mice.
AB  - BACKGROUND: The key factors which support re-expansion of beta cell numbers after
      injury are largely unknown. Insulin-like growth factor II (IGF-II) plays a
      critical role in supporting cell division and differentiation during ontogeny but
      its role in the adult is not known. In this study we investigated the effect of
      IGF-II on beta cell regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We employed an
      in vivo model of 'switchable' c-Myc-induced beta cell ablation, pIns-c
      MycER(TAM), in which 90% of beta cells are lost following 11 days of c-Myc (Myc)
      activation in vivo. Importantly, such ablation is normally followed by beta cell
      regeneration once Myc is deactivated, enabling functional studies of beta cell
      regeneration in vivo. IGF-II was shown to be re-expressed in the adult pancreas
      of pIns-c-MycER(TAM)/IGF-II(+/+) (MIG) mice, following beta cell injury. As
      expected in the presence of IGF-II beta cell mass and numbers recover rapidly
      after ablation. In contrast, in pIns-c-MycER(TAM)/IGF-II(+/-) (MIGKO) mice, which
      express no IGF-II, recovery of beta cell mass and numbers were delayed and
      impaired. Despite failure of beta cell number increase, MIGKO mice recovered from
      hyperglycaemia, although this was delayed. CONCLUSIONS/SIGNIFICANCE: Our results
      demonstrate that beta cell regeneration in adult mice depends on re-expression of
      IGF-II, and supports the utility of using such ablation-recovery models for
      identifying other potential factors critical for underpinning successful beta
      cell regeneration in vivo. The potential therapeutic benefits of manipulating the
      IGF-II signaling systems merit further exploration.

PMID- 22970136
TI  - Novel levamisole derivative induces extrinsic pathway of apoptosis in cancer
      cells and inhibits tumor progression in mice.
AB  - BACKGROUND: Levamisole, an imidazo(2,1-b)thiazole derivative, has been reported
      to be a potential antitumor agent. In the present study, we have investigated the
      mechanism of action of one of the recently identified analogues, 4a (2-benzyl-6
      (4'-fluorophenyl)-5-thiocyanato-imidazo[2,1-b][1], [3], [4]thiadiazole).
      MATERIALS AND METHODS: ROS production and expression of various apoptotic
      proteins were measured following 4a treatment in leukemia cell lines. Tumor
      animal models were used to evaluate the effect of 4a in comparison with
      Levamisole on progression of breast adenocarcinoma and survival.
      Immunohistochemistry and western blotting studies were performed to understand
      the mechanism of 4a action both ex vivo and in vivo. RESULTS: We have determined
      the IC(50) value of 4a in many leukemic and breast cancer cell lines and found
      CEM cells most sensitive (IC(50) 5 uM). Results showed that 4a treatment leads to
      the accumulation of ROS. Western blot analysis showed upregulation of pro
      apoptotic proteins t-BID and BAX, upon treatment with 4a. Besides, dose-dependent
      activation of p53 along with FAS, FAS-L, and cleavage of CASPASE-8 suggest that
      it induces death receptor mediated apoptotic pathway in CEM cells. More
      importantly, we observed a reduction in tumor growth and significant increase in
      survival upon oral administration of 4a (20 mg/kg, six doses) in mice. In
      comparison, 4a was found to be more potent than its parental analogue Levamisole
      based on both ex vivo and in vivo studies. Further, immunohistochemistry and
      western blotting studies indicate that 4a treatment led to abrogation of tumor
      cell proliferation and activation of apoptosis by the extrinsic pathway even in
      animal models. CONCLUSION: Thus, our results suggest that 4a could be used as a
      potent chemotherapeutic agent.

PMID- 22970137
TI  - Phototriggerable 2',7-caged paclitaxel.
AB  - Three different variants of photoactivatable caged paclitaxel (PTX) have been
      synthesized and their bioactivity was characterized in in vitro assays and in
      living cells. The caged PTXs contain the photoremovable chromophore 4,5-dimethoxy
      2-nitrobenzyloxycarbonyl (Nvoc) attached to position C7, C2' and to both of these
      positions via a carbonate bond. Single caged PTXs remained biologically active
      even at low dosages. Double caging was necessary in order to fully inhibit its
      activity and to obtain a phototriggerable PTX that can be applied successfully at
      commonly used concentrations. Irradiation of solutions containing the double
      caged PTX allowed dose-dependent delivery of functional PTX. Light-triggered
      stabilization of microtubule assemblies in vitro and in vivo by controlled light
      exposure of tubulin solutions or cell cultures containing caged PTX was
      demonstrated. Short light exposure under a fluorescence microscope allowed
      controlled delivery of free PTX during imaging.

PMID- 22970138
TI  - Identification and characterization of B-cell epitopes in the DBL4epsilon domain
      of VAR2CSA.
AB  - Malaria during pregnancy in Plasmodium falciparum endemic regions is a major
      cause of mortality and severe morbidity. VAR2CSA is the parasite ligand
      responsible for sequestration of Plasmodium falciparum infected erythrocytes to
      the receptor chondroitin sulfate A (CSA) in the placenta and is the leading
      candidate for a placental malaria vaccine. Antibodies induced in rats against the
      recombinant DBL4epsilon domain of VAR2CSA inhibit the binding of a number of
      laboratory and field parasite isolates to CSA. In this study, we used a
      DBL4epsilon peptide-array to identify epitopes targeted by DBL4epsilon-specific
      antibodies that inhibit CSA-binding of infected erythrocytes. We identified three
      regions of overlapping peptides which were highly antigenic. One peptide region
      distinguished itself particularly by showing a clear difference in the binding
      profile of highly parasite blocking IgG compared to the IgG with low capacity to
      inhibit parasite adhesion to CSA. This region was further characterized and
      together these results suggest that even though antibodies against the synthetic
      peptides which cover this region did not recognize native protein, the results
      using the mutant domain suggest that this linear epitope might be involved in the
      induction of inhibitory antibodies induced by the recombinant DBL4epsilon domain.

PMID- 22970139
TI  - Porphyromonas gingivalis FimA fimbriae: fimbrial assembly by fimA alone in the
      fim gene cluster and differential antigenicity among fimA genotypes.
AB  - The periodontal pathogen Porphyromonas gingivalis colonizes largely through FimA
      fimbriae, composed of polymerized FimA encoded by fimA. fimA exists as a single
      copy within the fim gene cluster (fim cluster), which consists of seven genes:
      fimX, pgmA and fimA-E. Using an expression vector, fimA alone was inserted into a
      mutant from which the whole fim cluster was deleted, and the resultant complement
      exhibited a fimbrial structure. Thus, the genes of the fim cluster other than
      fimA were not essential for the assembly of FimA fimbriae, although they were
      reported to influence FimA protein expression. It is known that there are various
      genotypes for fimA, and it was indicated that the genotype was related to the
      morphological features of FimA fimbriae, especially the length, and to the
      pathogenicity of the bacterium. We next complemented the fim cluster-deletion
      mutant with fimA genes cloned from P. gingivalis strains including genotypes I to
      V. All genotypes showed a long fimbrial structure, indicating that FimA itself
      had nothing to do with regulation of the fimbrial length. In FimA fimbriae
      purified from the complemented strains, types I, II, and III showed slightly
      higher thermostability than types IV and V. Antisera of mice immunized with each
      purified fimbria principally recognized the polymeric, structural conformation of
      the fimbriae, and showed low cross-reactivity among genotypes, indicating that
      FimA fimbriae of each genotype were antigenically different. Additionally, the
      activity of a macrophage cell line stimulated with the purified fimbriae was much
      lower than that induced by Escherichia coli lipopolysaccharide.

PMID- 22970140
TI  - Optimisation of prime-boost immunization in mice using novel protein-based and
      recombinant vaccinia (Tiantan)-based HBV vaccine.
AB  - BACKGROUND: A therapeutic vaccine for chronic hepatitis B virus (HBV) infection
      that enhances virus-specific cellular immune responses is urgently needed. The
      "prime-boost" regimen is a widely used vaccine strategy against many persistence
      infections. However, few reports have addressed this strategy applying for HBV
      therapeutic vaccine development. METHODOLOGY/PRINCIPAL FINDINGS: To develop an
      effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus
      (Tiantan) containing the S+PreS1 fusion antigen (RVJSS1) combined with the HBV
      particle-like subunit vaccine HBVSS1 to explore the most effective prime-boost
      regimen against HBV. The immune responses to different prime-boost regimens were
      assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine
      staining analysis. Among the combinations tested, an HBV protein particle vaccine
      priming and recombinant vaccinia virus boosting strategy accelerated specific
      seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres as
      well as the strongest multi-antigen (PreS1, and S)-specific cellular immune
      response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more
      significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF
      alpha and IFN-gamma). CONCLUSIONS: The HBSS1 protein-vaccine prime plus RVJSS1
      vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1
      like cytokines, and these immune responses may be important parameters for the
      future HBV therapeutic vaccines.

PMID- 22970141
TI  - Effects of speech clarity on recognition memory for spoken sentences.
AB  - Extensive research shows that inter-talker variability (i.e., changing the
      talker) affects recognition memory for speech signals. However, relatively little
      is known about the consequences of intra-talker variability (i.e. changes in
      speaking style within a talker) on the encoding of speech signals in memory. It
      is well established that speakers can modulate the characteristics of their own
      speech and produce a listener-oriented, intelligibility-enhancing speaking style
      in response to communication demands (e.g., when speaking to listeners with
      hearing impairment or non-native speakers of the language). Here we conducted two
      experiments to examine the role of speaking style variation in spoken language
      processing. First, we examined the extent to which clear speech provided benefits
      in challenging listening environments (i.e. speech-in-noise). Second, we compared
      recognition memory for sentences produced in conversational and clear speaking
      styles. In both experiments, semantically normal and anomalous sentences were
      included to investigate the role of higher-level linguistic information in the
      processing of speaking style variability. The results show that acoustic-phonetic
      modifications implemented in listener-oriented speech lead to improved speech
      recognition in challenging listening conditions and, crucially, to a substantial
      enhancement in recognition memory for sentences.

PMID- 22970142
TI  - Within-subject interlaboratory variability of QuantiFERON-TB gold in-tube tests.
AB  - BACKGROUND: The QuantiFERON(r)-TB Gold In-Tube test (QFT-GIT) is a viable
      alternative to the tuberculin skin test (TST) for detecting Mycobacterium
      tuberculosis infection. However, within-subject variability may limit test
      utility. To assess variability, we compared results from the same subjects when
      QFT-GIT enzyme-linked immunosorbent assays (ELISAs) were performed in different
      laboratories. METHODS: Subjects were recruited at two sites and blood was tested
      in three labs. Two labs used the same type of automated ELISA workstation, 8
      point calibration curves, and electronic data transfer. The third lab used a
      different automated ELISA workstation, 4-point calibration curves, and manual
      data entry. Variability was assessed by interpretation agreement and comparison
      of interferon-gamma (IFN-gamma) measurements. Data for subjects with discordant
      interpretations or discrepancies in TB Response >0.05 IU/mL were verified or
      corrected, and variability was reassessed using a reconciled dataset. RESULTS:
      Ninety-seven subjects had results from three labs. Eleven (11.3%) had discordant
      interpretations and 72 (74.2%) had discrepancies >0.05 IU/mL using unreconciled
      results. After correction of manual data entry errors for 9 subjects, and
      exclusion of 6 subjects due to methodological errors, 7 (7.7%) subjects were
      discordant. Of these, 6 (85.7%) had all TB Responses within 0.25 IU/mL of the
      manufacturer's recommended cutoff. Non-uniform error of measurement was observed,
      with greater variation in higher IFN-gamma measurements. Within-subject standard
      deviation for TB Response was as high as 0.16 IU/mL, and limits of agreement
      ranged from -0.46 to 0.43 IU/mL for subjects with mean TB Response within 0.25
      IU/mL of the cutoff. CONCLUSION: Greater interlaboratory variability was
      associated with manual data entry and higher IFN-gamma measurements. Manual data
      entry should be avoided. Because variability in measuring TB Response may affect
      interpretation, especially near the cutoff, consideration should be given to
      developing a range of values near the cutoff to be interpreted as "borderline,"
      rather than negative or positive.

PMID- 22970143
TI  - Individual spatial responses towards roads: implications for mortality risk.
AB  - BACKGROUND: Understanding the ecological consequences of roads and developing
      ways to mitigate their negative effects has become an important goal for many
      conservation biologists. Most mitigation measures are based on road mortality and
      barrier effects data. However, studying fine-scale individual spatial responses
      in roaded landscapes may help develop more cohesive road planning strategies for
      wildlife conservation. METHODOLOGY/PRINCIPAL FINDINGS: We investigated how
      individuals respond in their spatial behavior toward a highway and its traffic
      intensity by radio-tracking two common species particularly vulnerable to road
      mortality (barn owl Tyto alba and stone marten Martes foina). We addressed the
      following questions: 1) how highways affected home-range location and size in the
      immediate vicinity of these structures, 2) which road-related features influenced
      habitat selection, 3) what was the role of different road-related features on
      movement properties, and 4) which characteristics were associated with crossing
      events and road-kills. The main findings were: 1) if there was available habitat,
      barn owls and stone martens may not avoid highways and may even include highways
      within their home-ranges; 2) both species avoided using areas near the highway
      when traffic was high, but tended to move toward the highway when streams were in
      close proximity and where verges offered suitable habitat; and 3) barn owls
      tended to cross above-grade highway sections while stone martens tended to avoid
      crossing at leveled highway sections. CONCLUSIONS: Mortality may be the main road
      mediated mechanism that affects barn owl and stone marten populations. Fine-scale
      movements strongly indicated that a decrease in road mortality risk can be
      realized by reducing sources of attraction, and by increasing road permeability
      through measures that promote safe crossings.

PMID- 22970144
TI  - Synthesis and evaluation of a conjugate vaccine composed of Staphylococcus aureus
      poly-N-acetyl-glucosamine and clumping factor A.
AB  - The increasing frequency, severity and antimicrobial resistance of Staphylococcus
      aureus infections has made the development of immunotherapies against this
      pathogen more urgent than ever. Previous immunization attempts using monovalent
      antigens resulted in at best partial levels of protection against S. aureus
      infection. We therefore reasoned that synthesizing a bivalent conjugate vaccine
      composed of two widely expressed antigens of S. aureus would result in
      additive/synergetic activities by antibodies to each vaccine component and/or in
      increased strain coverage. For this we used reductive amination, to covalently
      link the S. aureus antigens clumping factor A (ClfA) and deacetylated poly-N-beta
      (1-6)-acetyl-glucosamine (dPNAG). Mice immunized with 1, 5 or 10 ug of the dPNAG
      ClfA conjugate responded in a dose-dependent manner with IgG to dPNAG and ClfA,
      whereas mice immunized with a mixture of ClfA and dPNAG developed significantly
      lower antibody titers to ClfA and no antibodies to PNAG. The dPNAG-ClfA vaccine
      was also highly immunogenic in rabbits, rhesus monkeys and a goat. Moreover,
      affinity-purified, antibodies to ClfA from dPNAG-ClfA immune serum blocked the
      binding of three S. aureus strains to immobilized fibrinogen. In an
      opsonophagocytic assay (OPKA) goat antibodies to dPNAG-ClfA vaccine, in the
      presence of complement and polymorphonuclear cells, killed S. aureus Newman and,
      to a lower extent, S. aureus Newman DeltaclfA. A PNAG-negative isogenic mutant
      was not killed. Moreover, PNAG antigen fully inhibited the killing of S. aureus
      Newman by antisera to dPNAG-ClfA vaccine. Finally, mice passively vaccinated with
      goat antisera to dPNAG-ClfA or dPNAG-diphtheria toxoid conjugate had comparable
      levels of reductions of bacteria in the blood 2 h after infection with three
      different S. aureus strains as compared to mice given normal goat serum. In
      conclusion, ClfA is an immunogenic carrier protein that elicited anti-adhesive
      antibodies that fail to augment the OPK and protective activities of antibodies
      to the PNAG cell surface polysaccharide.

PMID- 22970145
TI  - Long-term field data and climate-habitat models show that orangutan persistence
      depends on effective forest management and greenhouse gas mitigation.
AB  - BACKGROUND: Southeast Asian deforestation rates are among the world's highest and
      threaten to drive many forest-dependent species to extinction. Climate change is
      expected to interact with deforestation to amplify this risk. Here we examine
      whether regional incentives for sustainable forest management will be effective
      in improving threatened mammal conservation, in isolation and when combined with
      global climate change mitigation. METHODOLOGY/PRINCIPAL FINDINGS: Using a long
      time-series of orangutan nest counts for Sabah (2000-10), Malaysian Borneo, we
      evaluated the effect of sustainable forest management and climate change
      scenarios, and their interaction, on orangutan spatial abundance patterns. By
      linking dynamic land-cover and downscaled global climate model projections, we
      determine the relative influence of these factors on orangutan spatial abundance
      and use the resulting statistical models to identify habitat crucial for their
      long-term conservation. We show that land-cover change the degradation of primary
      forest had the greatest influence on orangutan population size. Anticipated
      climate change was predicted to cause reductions in abundance in currently
      occupied populations due to decreased habitat suitability, but also to promote
      population growth in western Sabah by increasing the suitability of presently
      unoccupied regions. CONCLUSIONS/SIGNIFICANCE: We find strong quantitative support
      for the Sabah government's proposal to implement sustainable forest management in
      all its forest reserves during the current decade; failure to do so could result
      in a 40 to 80 per cent regional decline in orangutan abundance by 2100. The Sabah
      orangutan is just one (albeit iconic) example of a forest-dependent species that
      stands to benefit from sustainable forest management, which promotes conservation
      of existing forests.

PMID- 22970146
TI  - Clinical audits in a postgraduate general practice training program: an
      evaluation of 8 years' experience.
AB  - BACKGROUND: Clinical audit can be of valuable assistance to any program which
      aims to improve the quality of health care and its delivery. Yet without a
      coherent strategy aimed at evaluating audits' effectiveness, valuable
      opportunities will be overlooked. Clinical audit projects are required as a part
      of the formative assessment of trainees in the Family Medicine Residency Program
      (FMRP) in Kuwait. This study was undertaken to draw a picture of trainees'
      understanding of the audit project with attention to the knowledge of audit
      theory and its educational significance and scrutinize the difficulties
      confronted during the experience. METHODOLOGY/PRINCIPAL FINDINGS: The materials
      included the records of 133 audits carried out by trainees and 165 post course
      questionnaires carried out between 2004 and 2011. They were reviewed and
      analyzed. The majority of audit projects were performed on diabetic (44.4%) and
      hypertensive (38.3%) care. Regarding audits done on diabetic care, they were
      carried out to assess doctors' awareness about screening for smoking status
      (8.6%), microalbuminuria (19.3%), hemoglobin A1c (15.5%), retinopathy (10.3%),
      dyslipidemia (15.8%), peripheral neuropathy (8.8%), and other problems (21.7%).
      As for audits concerning hypertensive care, they were carried out to assess
      doctors' awareness about screening for smoking status (38.0%), obesity (26.0%),
      dyslipidemia (12.0%), microalbuminuria (10.0%) and other problems (14.0%). More
      than half the participants (68.48%) who attended the audit course stated that
      they 'definitely agreed' about understanding the meaning of clinical audit. Most
      of them (75.8%) 'definitely agreed' about realizing the importance of clinical
      audit in improving patients' care. About half (49.7%) of them 'agreed' that they
      can distinguish between 'criteria' and 'standards'. CONCLUSION: The eight years
      of experience were beneficial. Trainees showed a good understanding of the idea
      behind auditing the services provided. They demonstrated their ability to improve
      the care given in health centers in which these projects were undertaken.

PMID- 22970147
TI  - A neonatal model of intravenous Staphylococcus epidermidis infection in mice <24
      h old enables characterization of early innate immune responses.
AB  - Staphylococcus epidermidis (SE) causes late onset sepsis and significant
      morbidity in catheterized preterm newborns. Animal models of SE infection are
      useful in characterizing disease mechanisms and are an important approach to
      developing improved diagnostics and therapeutics. Current murine models of
      neonatal bacterial infection employ intraperitoneal or subcutaneous routes at
      several days of age, and may, therefore, not accurately reflect distinct features
      of innate immune responses to bacteremia. In this study we developed, validated,
      and characterized a murine model of intravenous (IV) infection in neonatal mice
      <24 hours (h) old to describe the early innate immune response to SE. C57BL/6
      mice <24 h old were injected IV with 10(6), 10(7), 10(8) colony-forming units
      (CFU) of SE 1457, a clinical isolate from a central catheter infection. A
      prospective injection scoring system was developed and validated, with only high
      quality injections analyzed. Newborn mice were euthanized between 2 and 48 h post
      injection and spleen, liver, and blood collected to assess bacterial viability,
      gene expression, and cytokine production. High quality IV injections demonstrated
      inoculum-dependent infection of spleen, liver and blood. Within 2 h of injection,
      SE induced selective transcription of TLR2 and MyD88 in the liver, and increased
      systemic production of plasma IL-6 and TNF-alpha. Despite clearance of bacteremia
      and solid organ infection within 48 h, inoculum-dependent impairment in weight
      gain was noted. We conclude that a model of IV SE infection in neonatal mice <24
      h old is feasible, demonstrating inoculum-dependent infection of solid organs and
      a pattern of bacteremia, rapid and selective innate immune activation, and
      impairment of weight gain typical of infected human neonates. This novel model
      can now be used to characterize immune ontogeny, evaluate infection biomarkers,
      and assess preventative and therapeutic modalities.

PMID- 22970148
TI  - Distinct and contrasting transcription initiation patterns at Mycobacterium
      tuberculosis promoters.
AB  - Although sequencing of Mycobacterium tuberculosis genome lead to better
      understanding of transcription units and gene functions, interactions occurring
      during transcription initiation between RNA polymerase and promoters is yet to be
      elucidated. Different stages of transcription initiation include promoter
      specific binding of RNAP, isomerization, abortive initiation and promoter
      clearance. We have now analyzed these events with four promoters of M.
      tuberculosis viz. P(gyrB1), P(gyrR), P(rrnPCL1) and P(metU). The promoters
      differed from each other in their rates of open complex formation, decay,
      promoter clearance and abortive transcription. The equilibrium binding and
      kinetic studies of various steps revealed distinct rate limiting events for each
      of the promoter, which also differed markedly in their characteristics from the
      respective promoters of Mycobacterium smegmatis. Surprisingly, the transcription
      at gyr promoter was enhanced in the presence of initiating nucleotides and
      decreased in the presence of alarmone, pppGpp, a pattern typically seen with rRNA
      promoters studied so far. The gyr promoter of M. smegmatis, on the other hand,
      was not subjected to pppGpp mediated regulation. The marked differences in the
      transcription initiation pathway seen with rrn and gyr promoters of M. smegmatis
      and M. tuberculosis suggest that such species specific differences in the
      regulation of expression of the crucial housekeeping genes could be one of the
      key determinants contributing to the differences in growth rate and lifestyle of
      the two organisms. Moreover, the distinct rate limiting steps during
      transcription initiation of each one of the promoters studied point at variations
      in their intracellular regulation.

PMID- 22970149
TI  - Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9
      years: a randomized, controlled trial (the DOLAB Study).
AB  - BACKGROUND: Omega-3 fatty acids are dietary essentials, and the current low
      intakes in most modern developed countries are believed to contribute to a wide
      variety of physical and mental health problems. Evidence from clinical trials
      indicates that dietary supplementation with long-chain omega-3 may improve child
      behavior and learning, although most previous trials have involved children with
      neurodevelopmental disorders such as attention-deficit/hyperactivity disorder
      (ADHD) or developmental coordination disorder (DCD). Here we investigated whether
      such benefits might extend to the general child population. OBJECTIVES: To
      determine the effects of dietary supplementation with the long-chain omega-3
      docosahexaenoic acid (DHA) on the reading, working memory, and behavior of
      healthy schoolchildren. DESIGN: Parallel group, fixed-dose, randomized, double
      blind, placebo-controlled trial (RCT). SETTING: Mainstream primary schools in
      Oxfordshire, UK (n = 74). PARTICIPANTS: Healthy children aged 7-9 years initially
      underperforming in reading (<= 33(rd) centile). 1376 invited, 362 met study
      criteria. INTERVENTION: 600 mg/day DHA (from algal oil), or taste/color matched
      corn/soybean oil placebo. MAIN OUTCOME MEASURES: Age-standardized measures of
      reading, working memory, and parent- and teacher-rated behavior. RESULTS: ITT
      analyses showed no effect of DHA on reading in the full sample, but significant
      effects in the pre-planned subgroup of 224 children whose initial reading
      performance was <= 20(th) centile (the target population in our original study
      design). Parent-rated behavior problems (ADHD-type symptoms) were significantly
      reduced by active treatment, but little or no effects were seen for either
      teacher-rated behaviour or working memory. CONCLUSIONS: DHA supplementation
      appears to offer a safe and effective way to improve reading and behavior in
      healthy but underperforming children from mainstream schools. Replication studies
      are clearly warranted, as such children are known to be at risk of low
      educational and occupational outcomes in later life. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01066182 and Controlled-Trials.com ISRCTN99771026.

PMID- 22970150
TI  - Safety and tolerability of Lactobacillus reuteri DSM 17938 and effects on
      biomarkers in healthy adults: results from a randomized masked trial.
AB  - BACKGROUND: There are few carefully-designed studies investigating the safety of
      individual probiotics approved under Investigational New Drug policies.
      OBJECTIVES: The primary aim of this prospective, double-blind placebo-controlled
      trial was to investigate if daily treatment of adults with Lactobacillus reuteri
      DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to
      determine if LR treatment has immune effects as determined by regulatory T cell
      percentages, expression of toll-like receptors (TLR)-2 and -4 on circulating
      peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated
      PBMC, and intestinal inflammation as measured by fecal calprotectin. METHODS:
      Forty healthy adults were randomized to a daily dose of 5 * 10(8) CFUs of LR (n =
      30) or placebo (n = 10) for 2 months. Participants completed a daily diary card
      and had 7 clinic visits during treatment and observation. RESULTS: There were no
      severe adverse events (SAEs) and no significant differences in adverse events
      (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression
      after treatment. The probiotic-treated group had a significantly higher fecal
      calprotectin level than the placebo group after 2 months of treatment: 50 ug/g
      (IQR 24-127 ug/g) vs. 17 ug/g (IQR 11-26 ug/g), p = 0.03, although values
      remained in the normal clinical range (0-162.9 ug/g). LR vials retained >10(8)
      CFUs viable organisms/ml. CONCLUSIONS: LR is safe and well tolerated in adults,
      without significant changes in immunologic markers. There was a small but
      significant increase in fecal calprotectin, perhaps indicating some element of
      immune recognition at the intestinal level. TRIAL REGISTRATION: Clinical
      Trials.gov NCT00922727.

PMID- 22970151
TI  - Ectopic expression of Hrf1 enhances bacterial resistance via regulation of
      diterpene phytoalexins, silicon and reactive oxygen species burst in rice.
AB  - Harpin proteins as elicitor derived from plant gram negative bacteria such as
      Xanthomonas oryzae pv. oryzae (Xoo), Erwinia amylovora induce disease resistance
      in plants by activating multiple defense responses. However, it is unclear
      whether phytoalexin production and ROS burst are involved in the disease
      resistance conferred by the expression of the harpin(Xoo) protein in rice. In
      this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial
      blight. Accompanying with the activation of genes related to the phytoalexin
      biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and
      consistently accumulated concurrent with the limitation of bacterial growth rate.
      Moreover, the hrf1-transformed rice showed an increased ability for ROS
      scavenging and decreased hydrogen peroxide (H(2)O(2)) concentration. Furthermore,
      the localization and relative quantification of silicon deposition in rice leaves
      was detected by scanning electron microscopy (SEM) and energy-dispersive X-ray
      spectrometer (EDS). Finally, the transcript levels of defense response genes
      increased in transformed rice. These results show a correlation between Xoo
      resistance and phytoalexin production, H(2)O(2), silicon deposition and defense
      gene expression in hrf1-transformed rice. These data are significant because they
      provide evidence for a better understanding the role of defense responses in the
      incompatible interaction between bacterial disease and hrf1-transformed plants.
      These data also supply an opportunity for generating nonspecific resistance to
      pathogens.

PMID- 22970152
TI  - In silico identification of potent pancreatic triacylglycerol lipase inhibitors
      from traditional Chinese medicine.
AB  - Pancreatic triacylglycerol lipase (PNLIP) are primary lipases that are critical
      for triacylglyceride digestion in human. Since reduced metabolism of
      triacylglyceride might be a plausible concept for weight loss, we screened for
      potential PNLIP inhibitors from traditional Chinese medicine (TCM) with the aim
      to identify weight loss candidate compounds. TCM candidates Aurantiamide,
      Cnidiadin, and 2-hexadecenoic acid exhibited higher Dock Scores than the
      commercial drug Orlistat, and were also predicted to have inhibitory
      characteristics against PNLIP using constructed MLR (R(2) = 0.8664) and SVM (R(2)
      = 0.9030) models. Molecular dynamics indicated that the TCM-PNLIP complexes
      formed were stable. We identified that the PNLIP binding site has several
      residues that can serve as anchors, and a hydrophobic corridor that provides
      additional stability to the complex. Aurantiamide, Cnidiadin, and 2-hexadecenoic
      acid all have features that correspond to these binding site features, indicating
      their potential as candidates for PNLIP inhibitors. The information presented in
      this study may provide helpful insights to designing novel weight-control drugs.

PMID- 22970153
TI  - Marine mammal impacts in exploited ecosystems: would large scale culling benefit
      fisheries?
AB  - Competition between marine mammals and fisheries for marine resources-whether
      real or perceived-has become a major issue for several countries and in
      international fora. We examined trophic interactions between marine mammals and
      fisheries based on a resource overlap index, using seven Ecopath models including
      marine mammal groups. On a global scale, most food consumed by marine mammals
      consisted of prey types that were not the main target of fisheries. For each
      ecosystem, the primary production required (PPR) to sustain marine mammals was
      less than half the PPR to sustain fisheries catches. We also developed an index
      representing the mean trophic level of marine mammal's consumption (TL(Q)) and
      compared it with the mean trophic level of fisheries' catches (TL(C)). Our
      results showed that overall TL(Q) was lower than TL(C) (2.88 versus 3.42). As
      fisheries increasingly exploit lower-trophic level species, the competition with
      marine mammals may become more important. We used mixed trophic impact analysis
      to evaluate indirect trophic effects of marine mammals, and in some cases found
      beneficial effects on some prey. Finally, we assessed the change in the trophic
      structure of an ecosystem after a simulated extirpation of marine mammal
      populations. We found that this lead to alterations in the structure of the
      ecosystems, and that there was no clear and direct relationship between marine
      mammals' predation and the potential catch by fisheries. Indeed, total biomass,
      with no marine mammals in the ecosystem, generally remained surprisingly similar,
      or even decreased for some species.

PMID- 22970154
TI  - The Steppengrille (Gryllus spec./assimilis): selective filters and signal
      mismatch on two time scales.
AB  - In Europe, several species of crickets are available commercially as pet food.
      Here we investigated the calling song and phonotactic selectivity for sound
      patterns on the short and long time scales for one such a cricket, Gryllus spec.,
      available as "Gryllus assimilis", the Steppengrille, originally from Ecuador. The
      calling song consisted of short chirps (2-3 pulses, carrier frequency: 5.0 kHz)
      emitted with a pulse period of 30.2 ms and chirp rate of 0.43 per second. Females
      exhibited high selectivity on both time scales. The preference for pulse period
      peaked at 33 ms which was higher then the pulse period produced by males. Two
      consecutive pulses per chirp at the correct pulse period were already sufficient
      for positive phonotaxis. The preference for the chirp pattern was limited by
      selectivity for small chirp duty cycles and for chirp periods between 200 ms and
      500 ms. The long chirp period of the songs of males was unattractive to females.
      On both time scales a mismatch between the song signal of the males and the
      preference of females was observed. The variability of song parameters as
      quantified by the coefficient of variation was below 50% for all temporal
      measures. Hence, there was not a strong indication for directional selection on
      song parameters by females which could account for the observed mismatch. The
      divergence of the chirp period and female preference may originate from a founder
      effect, when the Steppengrille was cultured. Alternatively the mismatch was a
      result of selection pressures exerted by commercial breeders on low singing
      activity, to satisfy customers with softly singing crickets. In the latter case
      the prominent divergence between male song and female preference was the result
      of domestication and may serve as an example of rapid evolution of song traits in
      acoustic communication systems.

PMID- 22970155
TI  - Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer
      patients using gene sequencing and high resolution DNA melting analysis.
AB  - BACKGROUND: Ethnic variations in breast cancer epidemiology and genetics have
      necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in
      different populations. Knowledge of BRCA mutations in Chinese populations is
      still largely unknown. We conducted a multi-center study to characterize the
      spectra of BRCA mutations in Chinese breast and ovarian cancer patients from
      Southern China. METHODOLOGY/PRINCIPAL FINDINGS: A total of 651 clinically high
      risk breast and/or ovarian cancer patients were recruited from the Hong Kong
      Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1
      and BRCA2 mutation screening was performed using bi-directional sequencing of all
      coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house
      developed full high resolution DNA melting (HRM) analysis. Among the 451 probands
      analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in
      BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT,
      c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5%
      (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations
      (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted
      for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to
      confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM
      mutation screening for a panel of the founder mutations were developed and
      validated. CONCLUSION: In this study, our findings suggest that BRCA mutations
      account for a substantial proportion of hereditary breast/ovarian cancer in
      Southern Chinese population. Knowing the spectrum and frequency of the founder
      mutations in this population will assist in the development of a cost-effective
      rapid screening assay, which in turn facilitates genetic counseling and testing
      for the purpose of cancer risk assessment.

PMID- 22970156
TI  - Automated reconstruction algorithm for identification of 3D architectures of
      cribriform ductal carcinoma in situ.
AB  - Ductal carcinoma in situ (DCIS) is a pre-invasive carcinoma of the breast that
      exhibits several distinct morphologies but the link between morphology and
      patient outcome is not clear. We hypothesize that different mechanisms of growth
      may still result in similar 2D morphologies, which may look different in 3D. To
      elucidate the connection between growth and 3D morphology, we reconstruct the 3D
      architecture of cribriform DCIS from resected patient material. We produce a
      fully automated algorithm that aligns, segments, and reconstructs 3D
      architectures from microscopy images of 2D serial sections from human specimens.
      The alignment algorithm is based on normalized cross correlation, the
      segmentation algorithm uses histogram equilization, Otsu's thresholding, and
      morphology techniques to segment the duct and cribra. The reconstruction method
      combines these images in 3D. We show that two distinct 3D architectures are
      indeed found in samples whose 2D histological sections are similarly identified
      as cribriform DCIS. These differences in architecture support the hypothesis that
      luminal spaces may form due to different mechanisms, either isolated cell death
      or merging fronds, leading to the different architectures. We find that out of 15
      samples, 6 were found to have 'bubble-like' cribra, 6 were found to have 'tube
      like' criba and 3 were 'unknown.' We propose that the 3D architectures found,
      'bubbles' and 'tubes', account for some of the heterogeneity of the disease and
      may be prognostic indicators of different patient outcomes.

PMID- 22970157
TI  - n-Butylidenephthalide (BP) maintains stem cell pluripotency by activating
      Jak2/Stat3 pathway and increases the efficiency of iPS cells generation.
AB  - In 2006, induced pluripotent stem (iPS) cells were generated from somatic cells
      by introducing Oct4, Sox2, c-Myc and Klf4. The original process was inefficient;
      maintaining the pluripotency of embryonic stem (ES) and iPS cell cultures
      required an expensive reagent-leukemia induced factor (LIF). Our goal is to find
      a pure compound that not only maintains ES and iPS cell pluripotency, but also
      increases iPS cell generation efficiency. From 15 candidate compounds we
      determined that 10 ug/ml n-Butylidenephthalide (BP), an Angelica sinensis
      extract, triggers the up-regulation of Oct4 and Sox2 gene expression levels in
      MEF cells. We used ES and iPS cells treated with different concentrations of BP
      to test its usefulness for maintaining stem cell pluripotency. Results indicate
      higher expression levels of several stem cell markers in BP-treated ES and iPS
      cells compared to controls that did not contain LIF, including alkaline
      phosphatase, SSEA1, and Nanog. Embryoid body formation and differentiation
      results confirm that BP containing medium culture was capable of maintaining ES
      cell pluripotency after six time passage. Microarray analysis data identified
      PPAR, ECM, and Jak-Stat signaling as the top three deregulated pathways. We
      subsequently determined that phosphorylated Jak2 and phosphorylated Stat3 protein
      levels increased following BP treatment and suppressed with the Jak2 inhibitor,
      AG490. The gene expression levels of cytokines associated with the Jak2-Stat3
      pathway were also up-regulated. Last, we used pou5f1-GFP MEF cells to test iPS
      generation efficiency following BP treatment. Our data demonstrate the ability of
      BP to maintain stem cell pluripotency via the Jak2-Stat3 pathway by inducing
      cytokine expression levels, at the same time improving iPS generation efficiency.

PMID- 22970158
TI  - Optical rheology of porcine sclera by birefringence imaging.
AB  - PURPOSE: To investigate a relationship between birefringence and elasticity of
      porcine sclera ex vivo using polarization-sensitive optical coherence tomography
      (PS-OCT). METHODS: Elastic parameters and birefringence of 19 porcine eyes were
      measured. Four pieces of scleral strips which were parallel to the limbus, with a
      width of 4 mm, were dissected from the optic nerve head to the temporal side of
      each porcine eye. Birefringence of the sclera was measured with a prototype PS
      OCT. The strain and force were measured with a uniaxial material tester as the
      sample was stretched with a speed of 1.8 mm/min after preconditioning. A
      derivative of the exponentially-fitted stress-strain curve at 0% strain was
      extracted as the tangent modulus. Power of exponential stress-strain function was
      also extracted from the fitting. To consider a net stiffness of sclera,
      structural stiffness was calculated as a product of tangent modulus and
      thickness. Correlations between birefringence and these elastic parameters were
      examined. RESULTS: Statistically significant correlations between birefringence
      and all of the elastic parameters were found at 2 central positions. Structural
      stiffness and power of exponential stress-strain function were correlated with
      birefringence at the position near the optic nerve head. No correlation was found
      at the position near the equator. CONCLUSIONS: The evidence of correlations
      between birefringence and elasticity of sclera tested uniaxially was shown for
      the first time. This work may become a basis for in vivo measurement of scleral
      biomechanics using PS-OCT.

PMID- 22970159
TI  - Dietary salt reduction and cardiovascular disease rates in India: a mathematical
      model.
AB  - BACKGROUND: Reducing salt intake has been proposed to prevent cardiovascular
      disease in India. We sought to determine whether salt reductions would be
      beneficial or feasible, given the worry that unrealistically large reductions
      would be required, worsening iodine deficiency and benefiting only urban
      subpopulations. METHODS AND RESULTS: Future myocardial infarctions (MI) and
      strokes in India were predicted with a Markov model simulating men and women aged
      40 to 69 in both urban and rural locations, incorporating the risk reduction from
      lower salt intake. If salt intake does not change, we expect ~8.3 million MIs
      (95% CI: 6.9-9.6 million), 830,000 strokes (690,000-960,000) and 2.0 million
      associated deaths (1.5-2.4 million) per year among Indian adults aged 40 to 69
      over the next three decades. Reducing intake by 3 g/day over 30 years (-0.1
      g/year, 25% reduction) would reduce annual MIs by 350,000 (a 4.6% reduction; 95%
      CI: 320,000-380,000), strokes by 48,000 (-6.5%; 13,000-83,000) and deaths by
      81,000 (-4.9%; 59,000-100,000) among this group. The largest decline in MIs would
      be among younger urban men, but the greatest number of averted strokes would be
      among rural men, and nearly one-third of averted strokes and one-fifth of averted
      MIs would be among rural women. Only under a highly pessimistic scenario would
      iodine deficiency increase (by <0.0001%, ~1600 persons), since inadequate iodized
      salt access--not low intake of iodized salt--is the major cause of deficiency and
      would be unaffected by dietary salt reduction. CONCLUSIONS: Modest reductions in
      salt intake could substantially reduce cardiovascular disease throughout India.

PMID- 22970160
TI  - Cost per QALY (quality-adjusted life year) and lifetime cost of prolonged
      mechanical ventilation in Taiwan.
AB  - INTRODUCTION: Patients who require prolonged mechanical ventilation (PMV) are
      increasing and producing financial burdens worldwide. This study determines the
      cost per QALY (quality-adjusted life year), out-of-pocket expenses, and lifetime
      costs for PMV patients stratified by underlying diseases and cognition levels.
      METHODS: A nationwide sample of 50,481 patients with continual mechanical
      ventilation for more than 21 days was collected during 1997-2007. After
      stratifying the patients according to specific diagnoses, a latent class analysis
      (LCA) was performed to categorise PMV patients with multiple co-morbidities into
      several homogeneous groups. The survival functions were estimated for individual
      groups using the Kaplan-Meier method and extrapolated to 300 months through a
      semi-parametric method. The survival functions were adjusted using an EQ-5D
      utility value derived from a convenience sample of 142 PMV patients to estimate
      quality-adjusted life expectancies (QALE). Another convenience sample of 165
      patients was used to estimate the out-of-pocket expenses. The lifetime
      expenditures paid by the single-payer National Health Insurance (NHI) system and
      patients' families were estimated by multiplying average monthly expenditures by
      the survival probabilities and summing the values over lifetime. RESULTS: PMV
      therapy costs more than 100,000 U.S. dollars (USD) per QALY for all patients with
      poor cognition. For patients with partial cognition, PMV therapy costs less than
      56,000 USD per QALY for those with liver cirrhosis, intracranial or spinal cord
      injuries, and 57,000-69,000 USD for patients with multiple co-morbidities under
      age of 65. The average lifetime cost of PMV was usually below 56,000 USD. The out
      of-pocket expenses were often more than one-third of the total cost of treatment.
      CONCLUSIONS: PMV treatment for patients with poor cognition would cost more than
      5 times Taiwan's GDP (gross domestic products), or less cost-effective. The out
      of-pocket expenses for PMV provision should also be considered in policy
      decision.

PMID- 22970161
TI  - Exploring the mechanism of zanamivir resistance in a neuraminidase mutant: a
      molecular dynamics study.
AB  - It is critical to understand the molecular basis of the drug resistance of
      influenza viruses to efficiently treat this infectious disease. Recently, H1N1
      strains of influenza A carrying a mutation of Q136K in neuraminidase were found.
      The new strain showed a strong Zanamivir neutralization effect. In this study,
      normal molecular dynamics simulations and metadynamics simulations were employed
      to explore the mechanism of Zanamivir resistance. The wild-type neuraminidase
      contained a 3(10) helix before the 150 loop, and there was interaction between
      the 150 and 430 loops. However, the helix and the interaction between the two
      loops were disturbed in the mutant protein due to interaction between K136 and
      nearby residues. Hydrogen-bond network analysis showed weakened interaction
      between the Zanamivir drug and E276/D151 on account of the electrostatic
      interaction between K136 and D151. Metadynamics simulations showed that the free
      energy landscape was different in the mutant than in the wild-type neuraminidase.
      Conformation with the global minimum of free energy for the mutant protein was
      different from the wild-type conformation. While the drug fit completely into the
      active site of the wild-type neuraminidase, it did not match the active site of
      the mutant variant. This study indicates that the altered hydrogen-bond network
      and the deformation of the 150 loop are the key factors in development of
      Zanamivir resistance. Furthermore, the Q136K mutation has a variable effect on
      conformation of different N1 variants, with conformation of the 1918 N1 variant
      being more profoundly affected than that of the other N1 variants studied in this
      paper. This observation warrants further experimental investigation.

PMID- 22970162
TI  - Incidence and characteristics of bacteremia among children in rural Ghana.
AB  - The objective of the study was to describe systemic bacterial infections
      occurring in acutely ill and hospitalized children in a rural region in Ghana,
      regarding frequency, incidence, antimicrobial susceptibility patterns and
      associations with anthropometrical data.Blood cultures were performed in all
      children below the age of five years, who were admitted to Agogo Presbyterian
      Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009.
      Medical history and anthropometrical data were assessed using a standardized
      questionnaire at admission. Incidences were calculated after considering the
      coverage population adjusted for village-dependent health-seeking behavior.Among
      1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The
      four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%;
      n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%;
      n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of
      bacteremia was 46.6 cases/1,000 (CI 40.9-52.2). Yearly cumulative incidences per
      1,000 of the four most frequent isolates were 25.2 (CI 21.1-29.4) for NTS, 6.3
      (CI 4.1-8.4) for S. aureus, 4.3 (CI 2.5-6.1) for S. pneumoniae and 3.3 (CI 1.8
      4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia
      and systemic NTS bloodstream infection. Children older than three months had more
      often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100%
      of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both
      tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of
      Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic
      bacterial infections in nearly 20% of hospitalized children underline the need
      for microbiological diagnostics, to guide targeted antimicrobial treatment and
      prevention of bacteremia. If microbiological diagnostics are lacking, calculated
      antimicrobial treatment of severely ill children in malaria-endemic areas should
      be considered.

PMID- 22970163
TI  - alphaA-Crystallin-derived mini-chaperone modulates stability and function of
      cataract causing alphaAG98R-crystallin.
AB  - BACKGROUND: A substitution mutation in human alphaA-crystallin (alphaAG98R) is
      associated with autosomal dominant cataract. The recombinant mutant alphaAG98R
      protein exhibits altered structure, substrate-dependent chaperone activity,
      impaired oligomer stability and aggregation on prolonged incubation at 37 
      degrees C. Our previous studies have shown that alphaA-crystallin-derived mini
      chaperone (DFVIFLDVKHFSPEDLTVK) functions like a molecular chaperone by
      suppressing the aggregation of denaturing proteins. The present study was
      undertaken to determine the effect of alphaA-crystallin-derived mini-chaperone on
      the stability and chaperone activity of alphaAG98R-crystallin.
      METHODOLOGY/PRINCIPAL FINDINGS: Recombinant alphaAG98R was incubated in presence
      and absence of mini-chaperone and analyzed by chromatographic and spectrometric
      methods. Transmission electron microscope was used to examine the effect of mini
      chaperone on the aggregation propensity of mutant protein. Mini-chaperone
      containing photoactive benzoylphenylalanine was used to confirm the interaction
      of mini-chaperone with alphaAG98R. The rescuing of chaperone activity in
      mutantalpha-crystallin (alphaAG98R) by mini-chaperone was confirmed by chaperone
      assays. We found that the addition of the mini-chaperone during incubation of
      alphaAG98R protected the mutant crystallin from forming larger aggregates that
      precipitate with time. The mini-chaperone-stabilized alphaAG98R displayed
      chaperone activity comparable to that of wild-type alphaA-crystallin. The
      complexes formed between mini-alphaA-alphaAG98R complex and ADH were more stable
      than the complexes formed between alphaAG98R and ADH. Western-blotting and mass
      spectrometry confirmed the binding of mini-chaperone to mutant crystallin.
      CONCLUSION/SIGNIFICANCE: These results demonstrate that mini-chaperone stabilizes
      the mutant alphaA-crystallin and modulates the chaperone activity of alphaAG98R.
      These findings aid in our understanding of how to design peptide chaperones that
      can be used to stabilize mutant alphaA-crystallins and preserve the chaperone
      function.

PMID- 22970164
TI  - The involvement of thaumatin-like proteins in plant food cross-reactivity: a
      multicenter study using a specific protein microarray.
AB  - Cross-reactivity of plant foods is an important phenomenon in allergy, with
      geographical variations with respect to the number and prevalence of the
      allergens involved in this process, whose complexity requires detailed studies.
      We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity
      between fruit and pollen allergies. A representative panel of 16 purified TLPs
      was printed onto an allergen microarray. The proteins selected belonged to the
      sources most frequently associated with peach allergy in representative regions
      of Spain. Sera from two groups of well characterized patients, one with allergy
      to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant
      allergens (PAG), were obtained from seven geographical areas with different
      environmental pollen profiles. Cross-reactivity between members of this family
      was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed
      noticeable allergenic activity in the studied populations. Pru p 2.0201, the
      peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be
      allergens of probable relevance to fruit allergy, being mainly associated with
      pollen sensitization, and strongly linked to specific geographical areas such as
      Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited >50%
      positive response to Pru p 2.0201 and to chestnut TLP in these specific areas.
      Therefore, their recognition patterns were associated with the geographical area,
      suggesting a role for pollen in the sensitization of these allergens. Finally,
      the co-sensitizations of patients considering pairs of TLP allergens were
      analyzed by using the co-sensitization graph associated with an allergen
      microarray immunoassay. Our data indicate that TLPs are significant allergens in
      plant food allergy and should be considered when diagnosing and treating pollen
      food allergy.

PMID- 22970165
TI  - Bone marrow-derived mesenchymal stem cells repaired but did not prevent
      gentamicin-induced acute kidney injury through paracrine effects in rats.
AB  - This study evaluated the effects of bone marrow-derived mesenchymal stem cells
      (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute
      Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections
      of G up to 20 days. On the 10(th) day, injections of BMSCs, CM, CM+trypsin,
      CM+RNase or exosome-like microvesicles extracted from the CM were administered.
      In the prevention groups, the animals received the BMSCs 24 h before or on the
      5(th) day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were
      quantified. The kidneys were evaluated using hematoxylin/eosin staining and
      immunohystochemistry. The levels of Cr, U and FENa increased during all the
      periods of G treatment. The BMSC transplantation, its CM or exosome injections
      inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased
      cell proliferation. The pro-inflammatory cytokines decreased while the anti
      inflammatory cytokines increased compared to G. When the CM or its exosomes were
      incubated with RNase (but not trypsin), these effects were blunted. The Y
      chromosome was not observed in the 24-h prevention group, but it persisted in the
      kidney for all of the periods analyzed, suggesting that the injury is necessary
      for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs
      and CM minimized the G-induced renal damage through paracrine effects, most
      likely through the RNA carried by the exosome-like microvesicles. The use of the
      CM from BMSCs can be a potential therapeutic tool for this type of
      nephrotoxicity, allowing for the avoidance of cell transplantations.

PMID- 22970166
TI  - alpha-Tomatine-mediated anti-cancer activity in vitro and in vivo through cell
      cycle- and caspase-independent pathways.
AB  - alpha-Tomatine, a tomato glycoalkaloid, has been reported to possess antibiotic
      properties against human pathogens. However, the mechanism of its action against
      leukemia remains unclear. In this study, the therapeutic potential of alpha
      tomatine against leukemic cells was evaluated in vitro and in vivo. Cell
      viability experiments showed that alpha-tomatine had significant cytotoxic
      effects on the human leukemia cancer cell lines HL60 and K562, and the cells were
      found to be in the Annexin V-positive/propidium iodide-negative phase of cell
      death. In addition, alpha-tomatine induced both HL60 and K562 cell apoptosis in a
      cell cycle- and caspase-independent manner. alpha-Tomatine exposure led to a loss
      of the mitochrondrial membrane potential, and this finding was consistent with
      that observed on activation of the Bak and Mcl-1 short form (Mcl-1s) proteins.
      Exposure to alpha-tomatine also triggered the release of the apoptosis-inducing
      factor (AIF) from the mitochondria into the nucleus and down-regulated survivin
      expression. Furthermore, alpha-tomatine significantly inhibited HL60 xenograft
      tumor growth without causing loss of body weight in severe combined
      immunodeficiency (SCID) mice. Immunohistochemical test showed that the reduced
      tumor growth in the alpha-tomatine-treated mice was a result of increased
      apoptosis, which was associated with increased translocation of AIF in the
      nucleus and decreased survivin expression ex vivo. These results suggest that
      alpha-tomatine may be a candidate for leukemia treatment.

PMID- 22970167
TI  - The effect of environmental conditions on biofilm formation of Burkholderia
      pseudomallei clinical isolates.
AB  - Burkholderia pseudomallei, a Gram-negative saprophytic bacterium, is the
      causative agent of the potentially fatal melioidosis disease in humans. In this
      study, environmental parameters including temperature, nutrient content, pH and
      the presence of glucose were shown to play a role in in vitro biofilm formation
      by 28 B. pseudomallei clinical isolates, including four isolates with large
      colony variants (LCVs) and small colony variants (SCVs) morphotypes. Enhanced
      biofilm formation was observed when the isolates were tested in LB medium, at 30 
      degrees C, at pH 7.2, and in the presence of as little as 2 mM glucose
      respectively. It was also shown that all SVCs displayed significantly greater
      capacity to form biofilms than the corresponding LCVs when cultured in LB at 37 
      degrees C. In addition, octanoyl-homoserine lactone (C(8)-HSL), a quorum sensing
      molecule, was identified by mass spectrometry analysis in bacterial isolates
      referred to as LCV CTH, LCV VIT, SCV TOM, SCV CTH, 1 and 3, and the presence of
      other AHL's with higher masses; decanoyl-homoserine lactone (C(10)-HSL) and
      dodecanoyl-homoserine lactone (C(12)-HSL) were also found in all tested strain in
      this study. Last but not least, we had successfully acquired two Bacillus sp.
      soil isolates, termed KW and SA respectively, which possessed strong AHLs
      degradation activity. Biofilm formation of B. pseudomallei isolates was
      significantly decreased after treated with culture supernatants of KW and SA
      strains, demonstrating that AHLs may play a role in B. pseudomallei biofilm
      formation.

PMID- 22970168
TI  - Expression of MUC17 is regulated by HIF1alpha-mediated hypoxic responses and
      requires a methylation-free hypoxia responsible element in pancreatic cancer.
AB  - MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the
      digestive tract. Recent studies have demonstrated that the aberrant
      overexpression of MUC17 is correlated with the malignant potential of pancreatic
      ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17
      expression has yet to be identified. Here, we provide the first report of the
      MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor
      microenvironment and a driving force of cancer progression. Our data revealed
      that MUC17 was significantly induced by hypoxic stimulation through a hypoxia
      inducible factor 1alpha (HIF1alpha)-dependent pathway in some pancreatic cancer
      cells (e.g., AsPC1), whereas other pancreatic cancer cells (e.g., BxPC3)
      exhibited little response to hypoxia. Interestingly, these low-responsive cells
      have highly methylated CpG motifs within the hypoxia responsive element (HRE, 5'
      RCGTG-3'), a binding site for HIF1alpha. Thus, we investigated the demethylation
      effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low
      responsive cells with 5-aza-2'-deoxycytidine followed by additional hypoxic
      incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore,
      DNA methylation of HRE in pancreatic tissues from patients with PDACs showed
      higher hypomethylation status as compared to those from non-cancerous tissues,
      and hypomethylation was also correlated with MUC17 mRNA expression. Taken
      together, these findings suggested that the HIF1alpha-mediated hypoxic signal
      pathway contributes to MUC17 expression, and DNA methylation of HRE could be a
      determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells.

PMID- 22970169
TI  - Decrease of peripheral and intestinal NKG2A-positive T cells in patients with
      ulcerative colitis.
AB  - To investigate the role of inhibitory natural killer receptors (iNKRs) in
      inflammatory bowel disease (IBD), we analyzed the expression of NKG2A, one of the
      iNKRs, on T cells in a mouse colitis model and human IBD. During the active phase
      of dextran sulfate sodium (DSS)-induced mouse colitis, the frequency of NKG2A+ T
      cells was significantly decreased in the peripheral blood, and increased in the
      intestine, suggesting the mobilization of this T cell subset to the sites of
      inflammation. Administration of anti-NKG2A antibody increased the number of
      inflammatory foci in DSS-induced colitis, suggesting the involvement of NKG2A+ T
      cells in this colitis model. In ulcerative colitis (UC) patients, the frequency
      of peripheral blood NKG2A+ T cells was significantly decreased, compared with
      Crohn's disease (CD) patients and healthy controls, regardless of clinical
      conditions such as treatment modalities and disease activity. Notably, in sharp
      contrast to the DSS-induced mouse colitis model, the frequency of NKG2A+ cells
      among intestinal T cells was also decreased in UC patients. These results suggest
      that inadequate local infiltration of NKG2A+ T cells may be involved in the
      pathogenesis of UC.

PMID- 22970170
TI  - A novel in vivo siRNA delivery system specifically targeting liver cells for
      protection of ConA-induced fulminant hepatitis.
AB  - BACKGROUND: Fulminant hepatitis progresses to acute liver failure (ALF) when the
      extent of hepatocyte death exceeds the liver's regenerative capacity. Although
      small interfering RNA (siRNA) appears promising in animal models of hepatitis,
      the approach is limited by drawbacks associated with systemic administration of
      siRNA. The aim of this study is to develop a hepatocyte-specific delivery system
      of siRNA for treatment of fulminant hepatitis. METHODOLOGY/PRINCIPAL FINDINGS:
      Galactose-conjugated liposome nano-particles (Gal-LipoNP) bearing siRNA was
      prepared, and the particle size and zeta potential of Gal-LipoNP/siRNA complexes
      were measured. The distribution, cytotoxicity and gene silence efficiency were
      studied in vivo in a concanavalin A (ConA)-induced hepatitis model. C57BL/6 mice
      were treated with Gal-LipoNP Fas siRNA by i.v. injection 72 h before ConA
      challenge, and hepatocyte injury was evaluated using serum alanine transferase
      (ALT) and aspartate transaminase (AST) levels, as well as liver histopathology
      and TUNEL-positive hepatocytes. The galactose-ligated liposomes were capable of
      encapsulating >96% siRNA and exhibited a higher stability than naked siRNA in
      plasma. Hepatocyte-specific targeting was confirmed by in vivo delivery
      experiment, in which the majority of Gal-LipoNP-siRNA evaded nuclease digestion
      and accumulated in the liver as soon as 6 h after administration. In vivo gene
      silencing was significant in the liver after treatment of Gal-Lipo-siRNA. In the
      ConA-induced hepatitis model, serum levels of ALT and AST were significantly
      reduced in mice treated with Gal-lipoNP-siRNA as compared with control mice.
      Additionally, tissue histopathology and apoptosis showed an overall reduction of
      injury in the Gal-LipoNP siRNA-treated mice. CONCLUSIONS/SIGNIFICANCE: This study
      is the first to our knowledge to demonstrate reduction of hepatic injury by liver
      specific induction of RNA interference using Gal-LipoNP Fas siRNA, highlighting a
      novel RNAi-based therapeutic potential in many liver diseases.

PMID- 22970172
TI  - Molecular and cellular mechanisms of cigarette smoke-induced myocardial injury:
      prevention by vitamin C.
AB  - BACKGROUND: Cardiovascular disease (CVD) remains one of the major killers in
      modern society. One strong risk factor of CVD is cigarette smoking that causes
      myocardial injury and leads to the genesis of pathological cardiovascular events.
      However, the exact toxic component(s) of cigarette smoke (CS) and its molecular
      and cellular mechanisms for causing myocardial injury leading to heart damage and
      its prevention are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using a
      guinea pig model, here we show that chronic exposure to CS produces myocardial
      injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C
      deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to
      CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a
      smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air
      exposure instead of CS exposure under similar conditions. Myocardial injury was
      produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by
      release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation,
      apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat
      cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone
      (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor
      responsible for CS-induced myocardial damage. A moderately large dose of vitamin
      C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based
      studies indicated that plasma vitamin C levels of smokers without disease were
      significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS
      related cardiovascular patients were further lower (p = 0.0000) than that of
      smokers without disease. CONCLUSIONS/SIGNIFICANCE: The results indicate that
      dietary supplementation of vitamin C may be a novel and simple therapy for the
      prevention of pathological cardiovascular events in habitual smokers.

PMID- 22970171
TI  - Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in
      both cytidine deaminase domains of Apobec3G.
AB  - The mammalian two-hybrid system MAPPIT allows the detection of protein-protein
      interactions in intact human cells. We developed a random mutagenesis screening
      strategy based on MAPPIT to detect mutations that disrupt the interaction of one
      protein with multiple protein interactors simultaneously. The strategy was used
      to detect residues of the human cytidine deaminase Apobec3G that are important
      for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins.
      The strategy is able to identify the previously described head-to-head
      homodimerization interface in the N-terminal domain of Apobec3G. Our analysis
      further detects two new potential interaction surfaces in the N-and C-terminal
      domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization.

PMID- 22970173
TI  - Macrophages, nitric oxide and microRNAs are associated with DNA damage response
      pathway and senescence in inflammatory bowel disease.
AB  - BACKGROUND: Cellular senescence can be a functional barrier to carcinogenesis. We
      hypothesized that inflammation modulates carcinogenesis through senescence and
      DNA damage response (DDR). We examined the association between senescence and DDR
      with macrophage levels in inflammatory bowel disease (IBD). In vitro experiments
      tested the ability of macrophages to induce senescence in primary cells.
      Inflammation modulating microRNAs were identified in senescence colon tissue for
      further investigation. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative
      immunohistochemistry identified protein expression by colon cell type. Increased
      cellular senescence (HP1gamma; P = 0.01) or DDR (gammaH2A.X; P = 0.031, phospho
      Chk2, P = 0.014) was associated with high macrophage infiltration in UC. Co
      culture with macrophages (ANA-1) induced senescence in >80% of primary cells
      (fibroblasts MRC5, WI38), illustrating that macrophages induce senescence.
      Interestingly, macrophage-induced senescence was partly dependent on nitric oxide
      synthase, and clinically relevant NO* levels alone induced senescence. NO*
      induced DDR in vitro, as detected by immunofluorescence. In contrast to UC, we
      noted in Crohn's disease (CD) that senescence (HP1gamma; P<0.001) and DDR
      (gammaH2A.X; P<0.05, phospho-Chk2; P<0.001) were higher, and macrophages were not
      associated with senescence. We hypothesize that nitric oxide may modulate
      senescence in CD; epithelial cells of CD had higher levels of NOS2 expression
      than in UC (P = 0.001). Microarrays and quantitative-PCR identified miR-21
      expression associated with macrophage infiltration and NOS2 expression.
      CONCLUSIONS: Senescence was observed in IBD with senescence-associated beta
      galactosidase and HP1gamma. Macrophages were associated with senescence and DDR
      in UC, and in vitro experiments with primary human cells showed that macrophages
      induce senescence, partly through NO*, and that NO* can induce DDR associated
      with senescence. Future experiments will investigate the role of NO* and miR-21
      in senescence. This is the first study to implicate macrophages and nitrosative
      stress in a direct effect on senescence and DDR, which is relevant to many
      diseases of inflammation, cancer, and aging.

PMID- 22970174
TI  - A comparative transcriptome analysis identifying FGF23 regulated genes in the
      kidney of a mouse CKD model.
AB  - Elevations of circulating Fibroblast growth factor 23 (FGF23) are associated with
      adverse cardiovascular outcomes and progression of renal failure in chronic
      kidney disease (CKD). Efforts to identify gene products whose transcription is
      directly regulated by FGF23 stimulation of fibroblast growth factor receptors
      (FGFR)/alpha-Klotho complexes in the kidney is confounded by both systemic
      alterations in calcium, phosphorus and vitamin D metabolism and intrinsic
      alterations caused by the underlying renal pathology in CKD. To identify FGF23
      responsive genes in the kidney that might explain the association between FGF23
      and adverse outcomes in CKD, we performed comparative genome wide analysis of
      gene expression profiles in the kidney of the Collagen 4 alpha 3 null mice
      (Col4a3(-/-)) model of progressive kidney disease with kidney expression profiles
      of Hypophosphatemic (Hyp) and FGF23 transgenic mouse models of elevated FGF23.
      The different complement of potentially confounding factors in these models
      allowed us to identify genes that are directly targeted by FGF23. This analysis
      found that alpha-Klotho, an anti-aging hormone and FGF23 co-receptor, was
      decreased by FGF23. We also identified additional FGF23-responsive transcripts
      and activation of networks associated with renal damage and chronic inflammation,
      including lipocalin 2 (Lcn2), transforming growth factor beta (TGF-beta) and
      tumor necrosis factor-alpha (TNF-alpha) signaling pathways. Finally, we found
      that FGF23 suppresses angiotensin-converting enzyme 2 (ACE2) expression in the
      kidney, thereby providing a pathway for FGF23 regulation of the renin-angiotensin
      system. These gene products provide a possible mechanistic links between elevated
      FGF23 and pathways responsible for renal failure progression and cardiovascular
      diseases.

PMID- 22970175
TI  - A knowledge-based method for association studies on complex diseases.
AB  - Complex disorders are a class of diseases whose phenotypic variance is caused by
      the interplay of multiple genetic and environmental factors. Analyzing the
      complexity underlying the genetic architecture of such traits may help develop
      more efficient diagnostic tests and therapeutic protocols. Despite the continuous
      advances in revealing the genetic basis of many of complex diseases using genome
      wide association studies (GWAS), a major proportion of their genetic variance has
      remained unexplained, in part because GWAS are unable to reliably detect small
      individual risk contributions and to capture the underlying genetic
      heterogeneity. In this paper we describe a hypothesis-based method to analyze the
      association between multiple genetic factors and a complex phenotype. Starting
      from sets of markers selected based on preexisting biomedical knowledge, our
      method generates multi-marker models relevant to the biological process
      underlying a complex trait for which genotype data is available. We tested the
      applicability of our method using the WTCCC case-control dataset. Analyzing a
      number of biological pathways, the method was able to identify several immune
      system related multi-SNP models significantly associated with Rheumatoid
      Arthritis (RA) and Crohn's disease (CD). RA-associated multi-SNP models were also
      replicated in an independent case-control dataset. The method we present provides
      a framework for capturing joint contributions of genetic factors to complex
      traits. In contrast to hypothesis-free approaches, its results can be given a
      direct biological interpretation. The replicated multi-SNP models generated by
      our analysis may serve as a predictor to estimate the risk of RA development in
      individuals of Caucasian ancestry.

PMID- 22970176
TI  - Coevolution of trustful buyers and cooperative sellers in the trust game.
AB  - Many online marketplaces enjoy great success. Buyers and sellers in successful
      markets carry out cooperative transactions even if they do not know each other in
      advance and a moral hazard exists. An indispensable component that enables
      cooperation in such social dilemma situations is the reputation system. Under the
      reputation system, a buyer can avoid transacting with a seller with a bad
      reputation. A transaction in online marketplaces is better modeled by the trust
      game than other social dilemma games, including the donation game and the
      prisoner's dilemma. In addition, most individuals participate mostly as buyers or
      sellers; each individual does not play the two roles with equal probability.
      Although the reputation mechanism is known to be able to remove the moral hazard
      in games with asymmetric roles, competition between different strategies and
      population dynamics of such a game are not sufficiently understood. On the other
      hand, existing models of reputation-based cooperation, also known as indirect
      reciprocity, are based on the symmetric donation game. We analyze the trust game
      with two fixed roles, where trustees (i.e., sellers) but not investors (i.e.,
      buyers) possess reputation scores. We study the equilibria and the replicator
      dynamics of the game. We show that the reputation mechanism enables cooperation
      between unacquainted buyers and sellers under fairly generous conditions, even
      when such a cooperative equilibrium coexists with an asocial equilibrium in which
      buyers do not buy and sellers cheat. In addition, we show that not many buyers
      may care about the seller's reputation under cooperative equilibrium. Buyers'
      trusting behavior and sellers' reputation-driven cooperative behavior coevolve to
      alleviate the social dilemma.

PMID- 22970177
TI  - The study of HIV and antenatal care integration in pregnancy in Kenya: design,
      methods, and baseline results of a cluster-randomized controlled trial.
AB  - BACKGROUND: Despite strong evidence for the effectiveness of anti-retroviral
      therapy for improving the health of women living with HIV and for the prevention
      of mother-to-child transmission (PMTCT), HIV persists as a major maternal and
      child health problem in sub-Saharan Africa. In most settings antenatal care (ANC)
      services and HIV treatment services are offered in separate clinics. Integrating
      these services may result in better uptake of services, reduction of the time to
      treatment initiation, better adherence, and reduction of stigma.
      METHODOLOGY/PRINCIPAL FINDINGS: A prospective cluster randomized controlled trial
      design was used to evaluate the effects of integrating HIV treatment into ANC
      clinics at government health facilities in rural Kenya. Twelve facilities were
      randomized to provide either fully integrated services (ANC, PMTCT, and HIV
      treatment services all delivered in the ANC clinic) or non-integrated services
      (ANC clinics provided ANC and basic PMTCT services and referred clients to a
      separate HIV clinic for HIV treatment). During June 2009- March 2011, 1,172 HIV
      positive pregnant women were enrolled in the study. The main study outcomes are
      rates of maternal enrollment in HIV care and treatment, infant HIV testing
      uptake, and HIV-free infant survival. Baseline results revealed that the
      intervention and control cohorts were similar with respect to socio-demographics,
      male partner HIV testing, sero-discordance of the couple, obstetric history,
      baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial
      at low-resource rural health facilities included frequent staff turnover, stock
      outs of essential supplies, transportation challenges, and changes in national
      guidelines. CONCLUSIONS/SIGNIFICANCE: This is the first randomized trial of ANC
      and HIV service integration to be conducted in rural Africa. It is expected that
      the study will provide critical evidence regarding the implementation and
      effectiveness of this service delivery strategy, with important implications for
      programs striving to eliminate vertical transmission of HIV and improve maternal
      health. TRIAL REGISTRATION: ClinicalTrials.gov NCT00931216
      http://clinicaltrials.gov/ct2/show/NCT00931216.

PMID- 22970178
TI  - Pseudomonas aeruginosa exhibits frequent recombination, but only a limited
      association between genotype and ecological setting.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen and an important cause of
      infection, particularly amongst cystic fibrosis (CF) patients. While specific
      strains capable of patient-to-patient transmission are known, many infections
      appear to be caused by unique and unrelated strains. There is a need to
      understand the relationship between strains capable of colonising the CF lung and
      the broader set of P. aeruginosa isolates found in natural environments. Here we
      report the results of a multilocus sequence typing (MLST)-based study designed to
      understand the genetic diversity and population structure of an extensive
      regional sample of P. aeruginosa isolates from South East Queensland, Australia.
      The analysis is based on 501 P. aeruginosa isolates obtained from environmental,
      animal and human (CF and non-CF) sources with particular emphasis on isolates
      from the Lower Brisbane River and isolates from CF patients obtained from the
      same geographical region. Overall, MLST identified 274 different sequence types,
      of which 53 were shared between one or more ecological settings. Our analysis
      revealed a limited association between genotype and environment and evidence of
      frequent recombination. We also found that genetic diversity of P. aeruginosa in
      Queensland, Australia was indistinguishable from that of the global P. aeruginosa
      population. Several CF strains were encountered frequently in multiple ecological
      settings; however, the most frequently encountered CF strains were confined to CF
      patients. Overall, our data confirm a non-clonal epidemic structure and indicate
      that most CF strains are a random sample of the broader P. aeruginosa population.
      The increased abundance of some CF strains in different geographical regions is a
      likely product of chance colonisation events followed by adaptation to the CF
      lung and horizontal transmission among patients.

PMID- 22970179
TI  - Abnormal levels of Gadd45alpha in developing neocortex impair neurite outgrowth.
AB  - To better understand the short and long-term effects of stress on the developing
      cerebral cortex, it is necessary to understand how early stress response genes
      protect or permanently alter cells. One family of highly conserved, stress
      response genes is the growth arrest and DNA damage-45 (Gadd45) genes. The
      expression of these genes is induced by a host of genotoxic, drug, and
      environmental stressors. Here we examined the impact of altering the expression
      of Gadd45alpha (Gadd45a), a member of the Gadd45 protein family that is expressed
      throughout the developing cortices of mice and humans. To manipulate levels of
      Gadd45a protein in developing mouse cortex, we electroporated cDNA plasmids
      encoding either Gadd45a or Gadd45a shRNA to either overexpress or knockdown
      Gadd45a levels in the developing cortices of mice, respectively. The effects of
      these manipulations were assessed by examining the fates and morphologies of the
      labeled neurons. Gadd45a overexpression both in vitro and in vivo significantly
      impaired the morphology of neurons, decreasing neurite complexity, inducing soma
      hypertrophy and increasing cell death. Knockdown of Gadd45a partially inhibited
      neuronal migration and reduced neurite complexity, an effect that was reversed in
      the presence of an shRNA-resistant Gadd45a. Finally, we found that shRNA against
      MEKK4, a direct target of Gadd45a, also stunted neurite outgrowth. Our findings
      suggest that the expression of Gadd45a in normal, developing brain is tightly
      regulated and that treatments or environmental stimuli that alter its expression
      could produce significant changes in neuronal circuitry development.

PMID- 22970180
TI  - DNA methylation profiles of airway epithelial cells and PBMCs from healthy,
      atopic and asthmatic children.
AB  - BACKGROUND: Allergic inflammation is commonly observed in a number of conditions
      that are associated with atopy including asthma, eczema and rhinitis. However,
      the genetic, environmental or epigenetic factors involved in these conditions are
      likely to be different. Epigenetic modifications, such as DNA methylation, can be
      influenced by the environment and result in changes to gene expression.
      OBJECTIVES: To characterize the DNA methylation pattern of airway epithelial
      cells (AECs) compared to peripheral blood mononuclear cells (PBMCs) and to
      discern differences in methylation within each cell type amongst healthy, atopic
      and asthmatic subjects. METHODS: PBMCs and AECs from bronchial brushings were
      obtained from children undergoing elective surgery for non-respiratory
      conditions. The children were categorized as atopic, atopic asthmatic, non-atopic
      asthmatic or healthy controls. Extracted DNA was bisulfite treated and 1505 CpG
      loci across 807 genes were analyzed using the Illumina GoldenGate Methylation
      Cancer Panel I. Gene expression for a subset of genes was performed using RT-PCR.
      RESULTS: We demonstrate a signature set of CpG sites that are differentially
      methylated in AECs as compared to PBMCs regardless of disease phenotype. Of
      these, 13 CpG sites were specific to healthy controls, 8 sites were only found in
      atopics, and 6 CpGs were unique to asthmatics. We found no differences in the
      methylation status of PBMCs between disease phenotypes. In AECs derived from
      asthmatics compared to atopics, 8 differentially methylated sites were identified
      including CpGs in STAT5A and CRIP1. We demonstrate STAT5A gene expression is
      decreased whereas CRIP1 gene expression is elevated in the AECs from asthmatic
      compared to both healthy and atopic subjects. DISCUSSION: We characterized a cell
      specific DNA methylation signature for AECs compared to PBMCs regardless of
      asthmatic or atopic status. Our data highlight the importance of understanding
      DNA methylation in the epithelium when studying the epithelial contribution to
      asthma.

PMID- 22970181
TI  - Increased thalamic gamma band activity correlates with symptom relief following
      deep brain stimulation in humans with Tourette's syndrome.
AB  - Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric
      disorder, which is marked by persistent multiple motor and phonic tics. The
      disorder is highly disruptive and in some cases completely debilitating. For
      those with severe, treatment-refractory TS, deep brain stimulation (DBS) has
      emerged as a possible option, although its mechanism of action is not fully
      understood. We performed a longitudinal study of the effects of DBS on TS
      symptomatology while concomitantly examining neurophysiological dynamics. We
      present the first report of the clinical correlation between the presence of
      gamma band activity and decreased tic severity. Local field potential recordings
      from five subjects implanted in the centromedian nucleus (CM) of the thalamus
      revealed a temporal correlation between the power of gamma band activity and the
      clinical metrics of symptomatology as measured by the Yale Global Tic Severity
      Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short
      term stimulation also produced increases in gamma power. Our results suggest that
      modulation of gamma band activity in both long-term and short-term DBS of the CM
      is a key factor in mitigating the pathophysiology associated with TS.

PMID- 22970182
TI  - Novel insights into the echinoderm nervous system from histaminergic and
      FMRFaminergic-like cells in the sea cucumber Leptosynapta clarki.
AB  - Understanding of the echinoderm nervous system is limited due to its distinct
      organization in comparison to other animal phyla and by the difficulty in
      accessing it. The transparent and accessible, apodid sea cucumber Leptosynapta
      clarki provides novel opportunities for detailed characterization of echinoderm
      neural systems. The present study used immunohistochemistry against FMRFamide and
      histamine to describe the neural organization in juvenile and adult sea
      cucumbers. Histaminergic- and FMRFaminergic-like immunoreactivity is reported in
      several distinct cell types throughout the body of L. clarki. FMRFamide-like
      immunoreactive cell bodies were found in the buccal tentacles, esophageal region
      and in proximity to the radial nerve cords. Sensory-like cells in the tentacles
      send processes toward the circumoral nerve ring, while unipolar and bipolar cells
      close to the radial nerve cords display extensive processes in close association
      with muscle and other cells of the body wall. Histamine-like immunoreactivity was
      identified in neuronal somatas located in the buccal tentacles, circumoral nerve
      ring and in papillae distributed across the body. The tentacular cells send
      processes into the nerve ring, while the processes of cells in the body wall
      papillae extend to the surface epithelium and radial nerve cords. Pharmacological
      application of histamine produced a strong coordinated, peristaltic response of
      the body wall suggesting the role of histamine in the feeding behavior. Our
      immunohistochemical data provide evidence for extensive connections between the
      hyponeural and ectoneural nervous system in the sea cucumber, challenging
      previously held views on a clear functional separation of the sub-components of
      the nervous system. Furthermore, our data indicate a potential function of
      histamine in coordinated, peristaltic movements; consistent with feeding patterns
      in this species. This study on L. clarki illustrates how using a broader range of
      neurotransmitter systems can provide better insight into the anatomy, function
      and evolution of echinoderm nervous sytems.

PMID- 22970183
TI  - Enhanced periosteal and endocortical responses to axial tibial compression
      loading in conditional connexin43 deficient mice.
AB  - The gap junction protein, connexin43 (Cx43) is involved in mechanotransduction in
      bone. Recent studies using in vivo models of conditional Cx43 gene (Gja1)
      deletion in the osteogenic linage have generated inconsistent results, with Gja1
      ablation resulting in either attenuated or enhanced response to mechanical load,
      depending upon the skeletal site examined or the type of load applied. To gain
      further insights on Cx43 and mechanotransduction, we examined bone formation
      response at both endocortical and periosteal surfaces in 2-month-old mice with
      conditional Gja1 ablation driven by the Dermo1 promoter (cKO). Relative to wild
      type (WT) littermates, it requires a larger amount of compressive force to
      generate the same periosteal strain in cKO mice. Importantly, cKO mice activate
      periosteal bone formation at a lower strain level than do WT mice, suggesting an
      increased sensitivity to mechanical load in Cx43 deficiency. Consistently,
      trabecular bone mass also increases in mutant mice upon load, while it decreases
      in WT. On the other hand, bone formation actually decreases on the endocortical
      surface in WT mice upon application of axial mechanical load, and this response
      is also accentuated in cKO mice. These changes are associated with increase of
      Cox-2 in both genotypes and further decrease of Sost mRNA in cKO relative to WT
      bones. Thus, the response of bone forming cells to mechanical load differs
      between trabecular and cortical components, and remarkably between endocortical
      and periosteal envelopes. Cx43 deficiency enhances both the periosteal and
      endocortical response to mechanical load applied as axial compression in growing
      mice.

PMID- 22970184
TI  - Groundtruthing next-gen sequencing for microbial ecology-biases and errors in
      community structure estimates from PCR amplicon pyrosequencing.
AB  - Analysis of microbial communities by high-throughput pyrosequencing of SSU rRNA
      gene PCR amplicons has transformed microbial ecology research and led to the
      observation that many communities contain a diverse assortment of rare taxa-a
      phenomenon termed the Rare Biosphere. Multiple studies have investigated the
      effect of pyrosequencing read quality on operational taxonomic unit (OTU)
      richness for contrived communities, yet there is limited information on the
      fidelity of community structure estimates obtained through this approach. Given
      that PCR biases are widely recognized, and further unknown biases may arise from
      the sequencing process itself, a priori assumptions about the neutrality of the
      data generation process are at best unvalidated. Furthermore, post-sequencing
      quality control algorithms have not been explicitly evaluated for the accuracy of
      recovered representative sequences and its impact on downstream analyses,
      reducing useful discussion on pyrosequencing reads to their diversity and
      abundances. Here we report on community structures and sequences recovered for in
      vitro-simulated communities consisting of twenty 16S rRNA gene clones tiered at
      known proportions. PCR amplicon libraries of the V3-V4 and V6 hypervariable
      regions from the in vitro-simulated communities were sequenced using the Roche
      454 GS FLX Titanium platform. Commonly used quality control protocols resulted in
      the formation of OTUs with >1% abundance composed entirely of erroneous
      sequences, while over-aggressive clustering approaches obfuscated real, expected
      OTUs. The pyrosequencing process itself did not appear to impose significant
      biases on overall community structure estimates, although the detection limit for
      rare taxa may be affected by PCR amplicon size and quality control approach
      employed. Meanwhile, PCR biases associated with the initial amplicon generation
      may impose greater distortions in the observed community structure.

PMID- 22970185
TI  - Development and validation of a prognostic gene-expression signature for lung
      adenocarcinoma.
AB  - Although several prognostic signatures have been developed in lung cancer, their
      application in clinical practice has been limited because they have not been
      validated in multiple independent data sets. Moreover, the lack of common genes
      between the signatures makes it difficult to know what biological process may be
      reflected or measured by the signature. By using classical data exploration
      approach with gene expression data from patients with lung adenocarcinoma (n =
      186), we uncovered two distinct subgroups of lung adenocarcinoma and identified
      prognostic 193-gene gene expression signature associated with two subgroups. The
      signature was validated in 4 independent lung adenocarcinoma cohorts, including
      556 patients. In multivariate analysis, the signature was an independent
      predictor of overall survival (hazard ratio, 2.4; 95% confidence interval, 1.2 to
      4.8; p = 0.01). An integrated analysis of the signature revealed that E2F1 plays
      key roles in regulating genes in the signature. Subset analysis demonstrated that
      the gene signature could identify high-risk patients in early stage (stage I
      disease), and patients who would have benefit of adjuvant chemotherapy. Thus, our
      study provided evidence for molecular basis of clinically relevant two distinct
      two subtypes of lung adenocarcinoma.

PMID- 22970186
TI  - Virulence profiles of bacteremic extended-spectrum beta-lactamase-producing
      Escherichia coli: association with epidemiological and clinical features.
AB  - There is scarce data about the importance of phylogroups and virulence factors
      (VF) in bloodstream infections (BSI) caused by extended-spectrum beta-lactamase
      producing Escherichia coli (ESBLEC). A prospective multicenter Spanish cohort
      including 191 cases of BSI due to ESBLEC was studied. Phylogroups and 25 VF genes
      were investigated by PCR. ESBLEC were classified into clusters according to their
      virulence profiles. The association of phylogropus, VF, and clusters with
      epidemiological features were studied using multivariate analysis. Overall,
      57.6%, 26.7%, and 15.7% of isolates belonged to A/B1, D and B2 phylogroups,
      respectively. By multivariate analysis (adjusted OR [95% CI]), virulence cluster
      C2 was independently associated with urinary tract source (5.05 [0.96-25.48]);
      cluster C4 with sources other than urinary of biliary tract (2.89 [1.05-7.93]),
      and cluster C5 with BSI in non-predisposed patients (2.80 [0.99-7.93]). Isolates
      producing CTX-M-9 group ESBLs and from phylogroup D predominated among cluster C2
      and C5, while CTX-M-1 group of ESBL and phylogroup B2 predominantes among C4
      isolates. These results suggest that host factors and previous antimicrobial use
      were more important than phylogroup or specific VF in the occurrence of BSI due
      to ESBLEC. However, some associations between virulence clusters and some
      specific epidemiological features were found.

PMID- 22970187
TI  - Identification and characterization of a broadly cross-reactive HIV-1 human
      monoclonal antibody that binds to both gp120 and gp41.
AB  - Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs)
      may assist vaccine immunogen design. Here we report a novel human monoclonal
      antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of
      the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from
      various primary isolates, to membrane-associated Envs on transfected cells and
      HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion
      intermediate structures containing N-trimer structure, but did not bind to
      denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120
      D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs
      on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1
      primary isolates from different clades and all the SHIVs tested in assays based
      on infection of peripheral blood mononuclear cells (PBMCs) by replication
      competent virus, but was less potent in cell line-based pseudovirus assays. In
      contrast to CD4, m43 did not induce Env conformational changes upon binding
      leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5
      and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs,
      or increased gp120 shedding. The overall modest neutralization activity of m43 is
      likely due to the limited binding of m43 to functional Envs which could be
      increased by antibody engineering if needed. M43 may represent a new class of
      bnAbs targeting conformational epitopes overlapping structures on both gp120 and
      gp41. Its novel epitope and possibly new mechanism(s) of neutralization could
      helpdesign improved vaccine immunogens and candidate therapeutics.

PMID- 22970188
TI  - The role of coral-associated bacterial communities in Australian Subtropical
      White Syndrome of Turbinaria mesenterina.
AB  - Australian Subtropical White Syndrome (ASWS) is an infectious, temperature
      dependent disease of the subtropical coral Turbinaria mesenterina involving a
      hitherto unknown transmissible causative agent. This report describes significant
      changes in the coral associated bacterial community as the disease progresses
      from the apparently healthy tissue of ASWS affected coral colonies, to areas of
      the colony affected by ASWS lesions, to the dead coral skeleton exposed by ASWS.
      In an effort to better understand the potential roles of bacteria in the
      formation of disease lesions, the effect of antibacterials on the rate of lesion
      progression was tested, and both culture based and culture independent techniques
      were used to investigate the bacterial communities associated with colonies of T.
      mesenterina. Culture-independent analysis was performed using the Oligonucleotide
      Fingerprinting of Ribosomal Genes (OFRG) technique, which allowed a library of
      8094 cloned bacterial 16S ribosomal genes to be analysed. Interestingly, the
      bacterial communities associated with both healthy and disease affected corals
      were very diverse and ASWS associated communities were not characterized by a
      single dominant organism. Treatment with antibacterials had a significant effect
      on the rate of progress of disease lesions (p = 0.006), suggesting that bacteria
      may play direct roles as the causative agents of ASWS. A number of potential
      aetiological agents of ASWS were identified in both the culture-based and culture
      independent studies. In the culture-independent study an Alphaproteobacterium
      closely related to Roseovarius crassostreae, the apparent aetiological agent of
      juvenile oyster disease, was found to be significantly associated with disease
      lesions. In the culture-based study Vibrio harveyi was consistently associated
      with ASWS affected coral colonies and was not isolated from any healthy colonies.
      The differing results of the culture based and culture-independent studies
      highlight the importance of using both approaches in the investigation of
      microbial communities.

PMID- 22970189
TI  - Genetic characterisation of Malawian pneumococci prior to the roll-out of the
      PCV13 vaccine using a high-throughput whole genome sequencing approach.
AB  - BACKGROUND: Malawi commenced the introduction of the 13-valent pneumococcal
      conjugate vaccine (PCV13) into the routine infant immunisation schedule in
      November 2011. Here we have tested the utility of high throughput whole genome
      sequencing to provide a high-resolution view of pre-vaccine pneumococcal
      epidemiology and population evolutionary trends to predict potential future
      change in population structure post introduction. METHODS: One hundred and twenty
      seven (127) archived pneumococcal isolates from randomly selected adults and
      children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi
      underwent whole genome sequencing. RESULTS: The pneumococcal population was
      dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine
      introduction. PCV13 is likely to protect against 62.9% of all circulating
      invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular
      Epidemiology Network (PMEN) clones are now in circulation in Malawi which were
      previously undetected but the pandemic multidrug resistant PMEN1 lineage was not
      identified. Genome analysis identified a number of novel sequence types and
      serotype switching. CONCLUSIONS: High throughput genome sequencing is now
      feasible and has the capacity to simultaneously elucidate serotype, sequence type
      and as well as detailed genetic information. It enables population level
      characterization, providing a detailed picture of population structure and genome
      evolution relevant to disease control. Post-vaccine introduction surveillance
      supported by genome sequencing is essential to providing a comprehensive picture
      of the impact of PCV13 on pneumococcal population structure and informing future
      public health interventions.

PMID- 22970190
TI  - A chick model of retinal detachment: cone rich and novel.
AB  - BACKGROUND: Development of retinal detachment models in small animals can be
      difficult and expensive. Here we create and characterize a novel, cone-rich
      retinal detachment (RD) model in the chick. METHODOLOGY/PRINCIPAL FINDINGS:
      Retinal detachments were created in chicks between postnatal days 7 and 21 by
      subretinal injections of either saline (SA) or hyaluronic acid (HA). Injections
      were performed through a dilated pupil with observation via surgical microscope,
      using the fellow eye as a control. Immunohistochemical analyses were performed at
      days 1, 3, 7, 10 and 14 after retinal detachment to evaluate the cellular
      responses of photoreceptors, Muller glia, microglia and nonastrocytic inner
      retinal glia (NIRG). Cell proliferation was detected with bromodeoxyuridine
      (BrdU)-incorporation and by the expression of proliferating cell nuclear antigen
      (PCNA). Cell death was detected with terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL). As in mammalian models of RD, there is shortening of
      photoreceptor outer segments and mis-trafficking of photoreceptor opsins in areas
      of RD. Photoreceptor cell death was maximal 1 day after RD, but continued until
      14 days after RD. Muller glia up-regulated glial fibriliary acidic protein
      (GFAP), proliferated, showed interkinetic nuclear migration, and migrated to the
      subretinal space in areas of detachment. Microglia became reactive; they up
      regulated CD45, acquired amoeboid morphology, and migrated toward outer retina in
      areas of RD. Reactive NIRG cells accumulated in detached areas.
      CONCLUSIONS/SIGNIFICANCE: Subretinal injections of SA or HA in the chick eye
      successfully produced retinal detachments and cellular responses similar to those
      seen in standard mammalian models. Given the relatively large eye size, and
      considering the low cost, the chick model of RD offers advantages for high
      throughput studies.

PMID- 22970191
TI  - Analysis of candidate colitis genes in the Gdac1 locus of mice deficient in
      glutathione peroxidase-1 and -2.
AB  - BACKGROUND: Mice that are deficient for glutathione peroxidases 1 and 2 (GPX)
      show large variations in the penetrance and severity of colitis in C57BL/6J and
      129S1/SvImJ backgrounds. We mapped a locus contributing to this difference to
      distal chromosome 2 (~119-133 mbp) and named it glutathione peroxidase-deficiency
      associated colitis 1 (Gdac1). The aim of this study was to identify the best gene
      candidates within the Gdac1 locus contributing to the murine colitis phenotype.
      METHOD/PRINCIPAL FINDINGS: We refined the boundaries of Gdac1 to 118-125 mbp (95%
      confidence interval) by increasing sample size and marker density across the
      interval. The narrowed region contains 128 well-annotated protein coding genes
      but it excludes Fermt1, a human inflammatory bowel disease candidate that was
      within the original boundaries of Gdac1. The locus we identified may be the Cdcs3
      locus mapped by others studying IL10-knockout mice. Using in silico analysis of
      the 128 genes, based on published colon expression data, the relevance of
      pathways to colitis, gene mutations, presence of non-synonymous-single-nucleotide
      polymorphisms (nsSNPs) and whether the nsSNPs are predicted to have an impact on
      protein function or expression, we excluded 42 genes. Based on a similar
      analysis, twenty-five genes from the remaining 86 genes were analyzed for
      expression-quantitative-trait loci, and another 15 genes were excluded.
      CONCLUSION/SIGNIFICANCE: Among the remaining 10 genes, we identified Pla2g4f and
      Duox2 as the most likely colitis gene candidates, because GPX metabolizes PLA2G4F
      and DUOX2 products. Pla2g4f is a phospholipase A2 that has three potentially
      significant nsSNP variants and showed expression differences across mouse
      strains. PLA2G4F produces arachidonic acid, which is a substrate for
      lipoxygenases and, in turn, for GPXs. DUOX2 produces H(2)O(2) and may control
      microbial populations. DUOX-1 and -2 control microbial populations in mammalian
      lung and in the gut of several insects and zebrafish. Dysbiosis is a phenotype
      that differentiates 129S1/SvImJ from C57BL/6J and may be due to strain
      differences in DUOX2 activity.

PMID- 22970192
TI  - Suppression of IFN-induced transcription underlies IFN defects generated by
      activated Ras/MEK in human cancer cells.
AB  - Certain oncolytic viruses exploit activated Ras signaling in order to replicate
      in cancer cells. Constitutive activation of the Ras/MEK pathway is known to
      suppress the effectiveness of the interferon (IFN) antiviral response, which may
      contribute to Ras-dependent viral oncolysis. Here, we identified 10 human cancer
      cell lines (out of 16) with increased sensitivity to the anti-viral effects of
      IFN-alpha after treatment with the MEK inhibitor U0126, suggesting that the
      Ras/MEK pathway underlies their reduced sensitivity to IFN. To determine how
      Ras/MEK suppresses the IFN response in these cells, we used DNA microarrays to
      compare IFN-induced transcription in IFN-sensitive SKOV3 cells, moderately
      resistant HT1080 cells, and HT1080 cells treated with U0126. We found that 267
      genes were induced by IFN in SKOV3 cells, while only 98 genes were induced in
      HT1080 cells at the same time point. Furthermore, the expression of a distinct
      subset of IFN inducible genes, that included RIGI, GBP2, IFIT2, BTN3A3, MAP2,
      MMP7 and STAT2, was restored or increased in HT1080 cells when the cells were co
      treated with U0126 and IFN. Bioinformatic analysis of the biological processes
      represented by these genes revealed increased representation of genes involved in
      the anti-viral response, regulation of apoptosis, cell differentiation and
      metabolism. Furthermore, introduction of constitutively active Ras into IFN
      sensitive SKOV3 cells reduced their IFN sensitivity and ability to activate IFN
      induced transcription. This work demonstrates for the first time that activated
      Ras/MEK in human cancer cells induces downregulation of a specific subset of IFN
      inducible genes.

PMID- 22970193
TI  - Mapping the aetiology of non-malarial febrile illness in Southeast Asia through a
      systematic review--terra incognita impairing treatment policies.
AB  - BACKGROUND: An increasing use of point of care diagnostic tests that exclude
      malaria, coupled with a declining malaria burden in many endemic countries, is
      highlighting the lack of ability of many health systems to manage other causes of
      febrile disease. A lack of knowledge of distribution of these pathogens, and a
      lack of screening and point-of-care diagnostics to identify them, prevents
      effective management of these generally treatable contributors to disease burden.
      While prospective data collection is vital, an untapped body of knowledge already
      exists in the published health literature. METHODS: Focusing on the Mekong region
      of Southeast Asia, published data from 1986 to 2011 was screened to for frequency
      of isolation of pathogens implicated in aetiology of non-malarial febrile
      illness. Eligibility criteria included English-language peer-reviewed studies
      recording major pathogens for which specific management is likely to be
      warranted. Of 1,252 identified papers, 146 met inclusion criteria and were
      analyzed and data mapped. RESULTS: Data tended to be clustered around specific
      areas where research institutions operate, and where resources to conduct studies
      are greater. The most frequently reported pathogen was dengue virus (n = 70),
      followed by Orientia tsutsugamushi and Rickettsia species (scrub typhus/murine
      typhus/spotted fever group n = 58), Leptospira spp. (n = 35), Salmonella enterica
      serovar Typhi and Paratyphi (enteric fever n = 24), Burkholderia pseudomallei
      (melioidosis n = 14), and Japanese encephalitis virus (n = 18). Wide tracts with
      very little published data on aetiology of fever are apparent. DISCUSSION AND
      CONCLUSIONS: This mapping demonstrates a very heterogeneous distribution of
      information on the causes of fever in the Mekong countries. Further directed data
      collection to address gaps in the evidence-base, and expansion to a global
      database of pathogen distribution, is readily achievable, and would help define
      wider priorities for research and development to improve syndromic management of
      fever, prioritize diagnostic development, and guide empirical therapy.

PMID- 22970195
TI  - A genome-wide screen in yeast identifies specific oxidative stress genes required
      for the maintenance of sub-cellular redox homeostasis.
AB  - Maintenance of an optimal redox environment is critical for appropriate
      functioning of cellular processes and cell survival. Despite the importance of
      maintaining redox homeostasis, it is not clear how the optimal redox potential is
      sensed and set, and the processes that impact redox on a cellular/organellar
      level are poorly understood. The genetic bases of cellular redox homeostasis were
      investigated using a green fluorescent protein (GFP) based redox probe, roGFP2
      and a pH sensitive GFP-based probe, pHluorin. The use of roGFP2, in conjunction
      with pHluorin, enabled determination of pH-adjusted sub-cellular redox potential
      in a non-invasive and real-time manner. A genome-wide screen using both the non
      essential and essential gene collections was carried out in Saccharomyces
      cerevisiae using cytosolic-roGFP2 to identify factors essential for maintenance
      of cytosolic redox state under steady-state conditions. 102 genes of diverse
      function were identified that are required for maintenance of cytosolic redox
      state. Mutations in these genes led to shifts in the half-cell glutathione redox
      potential by 75-10 mV. Interestingly, some specific oxidative stress-response
      processes were identified as over-represented in the data set. Further
      investigation of the role of oxidative stress-responsive systems in sub-cellular
      redox homeostasis was conducted using roGFP2 constructs targeted to the
      mitochondrial matrix and peroxisome and E(GSH) was measured in cells in
      exponential and stationary phase. Analyses allowed for the identification of key
      redox systems on a sub-cellular level and the identification of novel genes
      involved in the regulation of cellular redox homeostasis.

PMID- 22970194
TI  - Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and
      mutant huntingtin phenotypes in Huntington's disease knock-in mice.
AB  - The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT)
      exhibits age-dependent tissue-specific expansion that correlates with disease
      onset in patients, implicating somatic expansion as a disease modifier and
      potential therapeutic target. Somatic HTT CAG expansion is critically dependent
      on proteins in the mismatch repair (MMR) pathway. To gain further insight into
      mechanisms of somatic expansion and the relationship of somatic expansion to the
      disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in
      mice (HdhQ111) with mice carrying a conditional (floxed) Msh2 allele and D9-Cre
      transgenic mice, in which Cre recombinase is expressed specifically in MSNs
      within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those
      neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to
      eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice.
      Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin
      phenotypes: the early nuclear localization of diffusely immunostaining mutant
      huntingtin was slowed; and the later development of intranuclear huntingtin
      inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a
      genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent
      phenotypes in mice. These data suggest that the selective vulnerability of MSNs
      may be at least in part contributed by the propensity for somatic expansion in
      these neurons, and imply that intervening in the expansion process is likely to
      have therapeutic benefit.

PMID- 22970196
TI  - Genetic variation in telomere maintenance genes, telomere length and breast
      cancer risk.
AB  - BACKGROUND: Telomeres at the ends of eukaryotic chromosomes play a critical role
      in maintaining the integrity and stability of the genome and participate in the
      initiation of DNA damage/repair responses. METHODS: We performed a case-control
      study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in
      telomere maintenance genes previously found to be significantly associated with
      breast cancer risk. We used sister-sets obtained from the New York site of the
      Breast Cancer Family Registry (BCFR). Among the 313 sister-sets, there were 333
      breast cancer cases and 409 unaffected sisters who were evaluated in the current
      study. We separately applied conditional logistic regression and generalized
      estimating equations (GEE) models to evaluate associations between the three SNPs
      and breast cancer risk within sister-sets. We examined the associations between
      genotype, covariates and telomere length among unaffected sisters using a GEE
      model. RESULTS: We found no significant associations between the three SNPs in
      telomere maintenance genes and breast cancer risk by both conditional logistic
      regression and GEE models, nor were these SNPs significantly related to telomere
      length. Among unaffected sisters, shortened telomeres were statistically
      significantly correlated with never hormone replacement therapy (HRT) use.
      Increased duration of HRT use was significantly associated with reduced telomere
      length. The means of telomere length were 0.77 (SD = 0.35) for never HRT use,
      0.67 (SD = 0.29) for HRT use < 5 yrs and 0.59 (SD = 0.24) for HRT use >= 5 yrs
      after adjusting for age of blood donation and race and ethnicity. CONCLUSIONS: We
      found that exogenous hormonal exposure was inversely associated with telomere
      length. No significant associations between genetic variants and telomere length
      or breast cancer risk were observed. These findings provide initial evidence to
      understand hormonal exposure in the regulation of telomere length and breast
      cancer risk but need replication in prospective studies.

PMID- 22970197
TI  - Trp RNA-binding attenuation protein: modifying symmetry and stability of a
      circular oligomer.
AB  - BACKGROUND: Subunit number is amongst the most important structural parameters
      that determine size, symmetry and geometry of a circular protein oligomer. The L
      tryptophan biosynthesis regulator, TRAP, present in several Bacilli, is a good
      model system for investigating determinants of the oligomeric state. A short
      segment of C-terminal residues defines whether TRAP forms an 11-mer or 12-mer
      assembly. To understand which oligomeric state is more stable, we examine the
      stability of several wild type and mutant TRAP proteins. METHODOLOGY/PRINCIPAL
      FINDINGS: Among the wild type B. stearothermophilus, B. halodurans and B.
      subtilis TRAP, we find that the former is the most stable whilst the latter is
      the least. Thermal stability of all TRAP is shown to increase with L-tryptophan
      concentration. We also find that mutant TRAP molecules that are truncated at the
      C-terminus - and hence induced to form 12-mers, distinct from their 11-mer wild
      type counterparts--have increased melting temperatures. We show that the same
      effect can be achieved by a point mutation S72N at a subunit interface, which
      leads to exclusion of C-terminal residues from the interface. Our findings are
      supported by dye-based scanning fluorimetry, CD spectroscopy, and by crystal
      structure and mass spectrometry analysis of the B. subtilis S72N TRAP.
      CONCLUSIONS/SIGNIFICANCE: We conclude that the oligomeric state of a circular
      protein can be changed by introducing a point mutation at a subunit interface.
      Exclusion (or deletion) of the C-terminus from the subunit interface has a major
      impact on properties of TRAP oligomers, making them more stable, and we argue
      that the cause of these changes is the altered oligomeric state. The more stable
      TRAP oligomers could be used in potential applications of TRAP in
      bionanotechnology.

PMID- 22970198
TI  - The development of a canine anorectal autotransplantation model based on blood
      supply: a preliminary case report.
AB  - Colostomy is conventionally the only treatment for anal dysfunction. Recently, a
      few trials of anorectal transplantation in animals have been published; however,
      further development of this technique is required. Moreover, it is crucial to
      perform this research in dogs, which resemble humans in anorectal anatomy and
      biology. We designed a canine anorectal transplantation model, wherein anorectal
      autotransplantation was performed by anastomoses of the rectum, inferior
      mesenteric artery (IMA) and vein, and pudendal nerves. Resting pressure in the
      anal canal and anal canal pressure fluctuation were measured before and after
      surgery. Graft pathology was examined three days after surgery. The anal blood
      supply was compared with that in three beagles using indocyanine green (ICG)
      fluorescence angiography. The anorectal graft had sufficient arterial blood
      supply from the IMA; however, the graft's distal end was congested and
      necrotized. Functional examination demonstrated reduced resting pressure and the
      appearance of an irregular anal canal pressure wave after surgery. ICG
      angiography showed that the pudendal arteries provided more blood flow than the
      IMA to the anal segment. This is the first canine model of preliminary anorectal
      autotransplantation, and it demonstrates the possibility of establishing a
      transplantation model in dogs using appropriate vascular anastomoses, thus
      contributing to the progress of anorectal transplantation.

PMID- 22970199
TI  - Homology modeling of dopamine D2 and D3 receptors: molecular dynamics refinement
      and docking evaluation.
AB  - Dopamine (DA) receptors, a class of G-protein coupled receptors (GPCRs), have
      been targeted for drug development for the treatment of neurological, psychiatric
      and ocular disorders. The lack of structural information about GPCRs and their
      ligand complexes has prompted the development of homology models of these
      proteins aimed at structure-based drug design. Crystal structure of human
      dopamine D(3) (hD(3)) receptor has been recently solved. Based on the hD(3)
      receptor crystal structure we generated dopamine D(2) and D(3) receptor models
      and refined them with molecular dynamics (MD) protocol. Refined structures,
      obtained from the MD simulations in membrane environment, were subsequently used
      in molecular docking studies in order to investigate potential sites of
      interaction. The structure of hD(3) and hD(2L) receptors was differentiated by
      means of MD simulations and D(3) selective ligands were discriminated, in terms
      of binding energy, by docking calculation. Robust correlation of computed and
      experimental K(i) was obtained for hD(3) and hD(2L) receptor ligands. In
      conclusion, the present computational approach seems suitable to build and refine
      structure models of homologous dopamine receptors that may be of value for
      structure-based drug discovery of selective dopaminergic ligands.

PMID- 22970200
TI  - Fixed differences in the paralytic gene define two lineages within the Lutzomyia
      longipalpis complex producing different types of courtship songs.
AB  - The sand fly Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae), the
      most important vector of American visceral leishmaniasis, is widely distributed
      in Latin America. There is currently a consensus that it represents a species
      complex, however, the number and distribution of the different siblings is still
      uncertain. Previous analyses have indicated that Brazilian populations of this
      vector can be divided into two main groups according to the type of courtship
      song (Burst vs. Pulse) males produce during copulation. Nevertheless, no
      diagnostic differences have been observed between these two groups with most
      molecular markers used to date. We analyzed the molecular divergence in a
      fragment of the paralytic (para) gene, a locus involved in the control of
      courtship songs in Drosophila, among a number of Lu. longipalpis populations from
      Brazil producing Burst and Pulse-type songs. Our results revealed a very high
      level of divergence and fixed differences between populations producing the two
      types of songs. We also compared Lu. longipalpis with a very closely related
      species, Lutzomyia cruzi, which produces Burst-type songs. The results indicated
      a higher number of fixed differences between Lu. cruzi and the Pulse-type
      populations of Lu. longipalpis than with those producing Burst-type songs. The
      data confirmed our previous assumptions that the presence of different sibling
      species of the Lu. longipalpis complex in Brazil can be divided into two main
      groups, one representing a single species and a second more heterogeneous group
      that probably represents a number of incipient species. We hypothesize that para
      might be one of the genes directly involved in the control of the courtship song
      differences between these two groups or that it is linked to other loci
      associated with reproductive isolation of the Brazilian species.

PMID- 22970201
TI  - Distribution of high-risk human papillomavirus genotypes among HIV-negative women
      with and without cervical intraepithelial neoplasia in South Africa.
AB  - OBJECTIVE: Large studies describing the profile of high-risk Human papillomavirus
      (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe
      the prevalence and distribution of hrHPV genotypes among HIV-negative women in
      South Africa, with and without cervical intraepithelial neoplasia (CIN). METHODS:
      We report data on 8,050 HIV-negative women, aged 17-65 years, recruited into
      three sequential studies undertaken in Cape Town, South Africa. Women had no
      history of previous cervical cancer screening. Cervical samples were tested for
      hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were
      genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and
      biopsy/endocervical curettage to determine CIN status. The prevalence and
      distribution of specific hrHPV genotypes were examined by age and CIN status.
      RESULTS: Overall, 20.7% (95% CI, 19.9-21.6%) of women were hrHPV-positive by HC2,
      with women with CIN having the highest rates of positivity. Prevalence decreased
      with increasing age among women without CIN; but, a bimodal age curve was
      observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes
      in all age and CIN groups. HPV 45 became more frequent among older women with CIN
      grade 2 or 3 (CIN2,3). Younger women (17-29 years) had more multiple hrHPV
      genotypes overall and in each cervical disease group than older women (40-65
      years). CONCLUSION: HPV 16, 35, and 45 were the leading contributors to CIN 2,3.
      The current HPV vaccines could significantly reduce HPV-related cervical disease;
      however, next generation vaccines that include HPV 35 and 45 would further reduce
      cervical disease in this population.

PMID- 22970202
TI  - Towards a novel monitor of intraoperative awareness: selecting paradigm settings
      for a movement-based brain-computer interface.
AB  - During 0.1-0.2% of operations with general anesthesia, patients become aware
      during surgery. Unfortunately, pharmacologically paralyzed patients cannot seek
      attention by moving. Their attempted movements may however induce detectable EEG
      changes over the motor cortex. Here, methods from the area of movement-based
      brain-computer interfacing are proposed as a novel direction in anesthesia
      monitoring. Optimal settings for development of such a paradigm are studied to
      allow for a clinically feasible system. A classifier was trained on recorded EEG
      data of ten healthy non-anesthetized participants executing 3-second movement
      tasks. Extensive analysis was performed on this data to obtain an optimal EEG
      channel set and optimal features for use in a movement detection paradigm. EEG
      during movement could be distinguished from EEG during non-movement with very
      high accuracy. After a short calibration session, an average classification rate
      of 92% was obtained using nine EEG channels over the motor cortex, combined
      movement and post-movement signals, a frequency resolution of 4 Hz and a
      frequency range of 8-24 Hz. Using Monte Carlo simulation and a simple decision
      making paradigm, this translated into a probability of 99% of true positive
      movement detection within the first two and a half minutes after movement onset.
      A very low mean false positive rate of <0.01% was obtained. The current results
      corroborate the feasibility of detecting movement-related EEG signals, bearing in
      mind the clinical demands for use during surgery. Based on these results further
      clinical testing can be initiated.

PMID- 22970203
TI  - Serine-71 phosphorylation of Rac1 modulates downstream signaling.
AB  - The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by
      signaling to different signal pathways. It is believed that the presence of a
      specific effector at the location of GTPase activation determines the route of
      downstream signaling. We previously reported about EGF-induced Ser-71
      phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1
      and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to
      selected effector proteins. Binding of the constitutively active (Q61L) variants
      of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP,
      respectively, as well as to their common effector protein PAK was abrogated when
      Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction
      with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly
      affected. This ambivalent behaviour was obvious in functional assays. In contrast
      to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased
      membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is
      in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In
      addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate
      PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF
      kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated
      Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at
      serine-71 represents a reversible mechanism to shift specificity of
      GTPase/effector coupling, and to preferentially address selected downstream
      pathways.

PMID- 22970205
TI  - Elevation-dependent temperature trends in the Rocky Mountain Front Range: changes
      over a 56- and 20-year record.
AB  - Determining the magnitude of climate change patterns across elevational gradients
      is essential for an improved understanding of broader climate change patterns and
      for predicting hydrologic and ecosystem changes. We present temperature trends
      from five long-term weather stations along a 2077-meter elevational transect in
      the Rocky Mountain Front Range of Colorado, USA. These trends were measured over
      two time periods: a full 56-year record (1953-2008) and a shorter 20-year (1989
      2008) record representing a period of widely reported accelerating change. The
      rate of change of biological indicators, season length and accumulated growing
      degree days, were also measured over the 56 and 20-year records. Finally, we
      compared how well interpolated Parameter-elevation Regression on Independent
      Slopes Model (PRISM) datasets match the quality controlled and weather data from
      each station. Our results show that warming signals were strongest at mid
      elevations over both temporal scales. Over the 56-year record, most sites show
      warming occurring largely through increases in maximum temperatures, while the 20
      year record documents warming associated with increases in maximum temperatures
      at lower elevations and increases in minimum temperatures at higher elevations.
      Recent decades have also shown a shift from warming during springtime to warming
      in July and November. Warming along the gradient has contributed to increases in
      growing-degree days, although to differing degrees, over both temporal scales.
      However, the length of the growing season has remained unchanged. Finally, the
      actual and the PRISM interpolated yearly rates rarely showed strong correlations
      and suggest different warming and cooling trends at most sites. Interpretation of
      climate trends and their seasonal biases in the Rocky Mountain Front Range are
      dependent on both elevation and the temporal scale of analysis. Given mismatches
      between interpolated data and the directly measured station data, we caution
      against an over-reliance on interpolation methods for documenting local patterns
      of climatic change.

PMID- 22970204
TI  - A multiscale, mechanism-driven, dynamic model for the effects of 5alpha-reductase
      inhibition on prostate maintenance.
AB  - A systems-level mathematical model is presented that describes the effects of
      inhibiting the enzyme 5alpha-reductase (5aR) on the ventral prostate of the adult
      male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is
      essential for androgen regulation in males, both in normal conditions and disease
      states. The hormone kinetics and downstream effects on reproductive organs
      associated with perturbing androgen regulation are complex and not necessarily
      intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the
      potent androgen 5alpha-dihydrotestosterone (DHT). This results in decreased cell
      proliferation, fluid production and 5aR expression as well as increased apoptosis
      in the ventral prostate. These regulatory changes collectively result in
      decreased prostate size and function, which can be beneficial to men suffering
      from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer.
      There are two distinct isoforms of 5aR in male humans and rats, and thus
      developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on
      the market for treatment of BPH, including finasteride and dutasteride. In this
      effort, comparisons of simulated vs. experimental T and DHT levels and prostate
      size are depicted, demonstrating the model accurately described an approximate
      77% decrease in prostate size and nearly complete depletion of prostatic DHT
      following 21 days of daily finasteride dosing in rats. This implies T alone is
      not capable of maintaining a normal prostate size. Further model analysis
      suggests the possibility of alternative dosing strategies resulting in similar or
      greater effects on prostate size, due to complex kinetics between T, DHT and gene
      occupancy. With appropriate scaling and parameterization for humans, this model
      provides a multiscale modeling platform for drug discovery teams to test and
      generate hypotheses about drugging strategies for indications like BPH and
      prostate cancer, such as compound binding properties, dosing regimens, and target
      validation.

PMID- 22970206
TI  - The effect of aquatic plant abundance on shell crushing resistance in a
      freshwater snail.
AB  - Most of the shell material in snails is composed of calcium carbonate but the
      organic shell matrix determines the properties of calcium carbonate crystals. It
      has been shown that the deposition of calcium carbonate is affected by the
      ingestion of organic compounds. We hypothesize that organic compounds not
      synthesized by the snails are important for shell strength and must be obtained
      from the diet. We tested this idea indirectly by evaluating whether the abundance
      of the organic matter that snails eat is related to the strength of their shells.
      We measured shell crushing resistance in the snail Mexipyrgus churinceanus and
      the abundance of the most common aquatic macrophyte, the water lily Nymphaea
      ampla, in ten bodies of water in the valley of Cuatro Cienegas, Mexico. We used
      stable isotopes to test the assumption that these snails feed on water lily
      organic matter. We also measured other factors that can affect crushing
      resistance, such as the density of crushing predators, snail density, water pH,
      and the concentration of calcium and phosphorus in the water. The isotope
      analysis suggested that snails assimilate water lily organic matter that is
      metabolized by sediment bacteria. The variable that best explained the variation
      in crushing resistance found among sites was the local abundance of water lilies.
      We propose that the local amount of water lily organic matter provides organic
      compounds important in shell biomineralization, thus determining crushing
      resistance. Hence, we propose that a third trophic level could be important in
      the coevolution of snail defensive traits and predatory structures.

PMID- 22970207
TI  - Novel African trypanocidal agents: membrane rigidifying peptides.
AB  - The bloodstream developmental forms of pathogenic African trypanosomes are
      uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal
      activity is conferred by peptide hydrophobicity and charge distribution and
      results from increased rigidity of the plasma membrane. Structural analysis of
      lipid-associated peptide suggests a mechanism of phospholipid clamping in which
      an internal hydrophobic bulge anchors the peptide in the membrane and positively
      charged moieties at the termini coordinate phosphates of the polar lipid
      headgroups. This mechanism reveals a necessary phenotype in bloodstream form
      African trypanosomes, high membrane fluidity, and we suggest that targeting the
      plasma membrane lipid bilayer as a whole may be a novel strategy for the
      development of new pharmaceutical agents. Additionally, the peptides we have
      described may be valuable tools for probing the biosynthetic machinery
      responsible for the unique composition and characteristics of African trypanosome
      plasma membranes.

PMID- 22970208
TI  - Prospective identification of glioblastoma cells generating dormant tumors.
AB  - Although dormant tumors are highly prevalent within the human population, the
      underlying mechanisms are still mostly unknown. We have previously identified the
      consensus gene expression pattern of dormant tumors. Here, we show that this gene
      expression signature could be used for the isolation and identification of clones
      which generate dormant tumors. We established single cell-derived clones from the
      aggressive tumor-generating U-87 MG human glioblastoma cell line. Based only on
      the expression pattern of genes which were previously shown to be associated with
      tumor dormancy, we identified clones which generate dormant tumors. We show that
      very high expression levels of thrombospondin and high expression levels of
      angiomotin and insulin-like growth factor binding protein 5 (IGFBP5), together
      with low levels of endothelial specific marker (ESM) 1 and epithelial growth
      factor receptor (EGFR) characterize the clone which generates dormant U-87 MG
      derived glioblastomas. These tumors remained indolent both in subcutaneous and
      orthotopic intracranial sites, in spite of a high prevalence of proliferating
      cells. We further show that tumor cells which form U-87 MG derived dormant tumors
      have an impaired angiogenesis potential both in vitro and in vivo and have a
      slower invasion capacity. This work demonstrates that fast-growing tumors contain
      tumor cells that when isolated will form dormant tumors and serves as a proof-of
      concept for the use of transcriptome profiles in the identification of such
      cells. Isolating the tumor cells that form dormant tumors will facilitate
      understanding of the underlying mechanisms of dormant micro-metastases, late
      recurrence, and changes in rate of tumor progression.

PMID- 22970209
TI  - Plasma miR-601 and miR-760 are novel biomarkers for the early detection of
      colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is a major cause of death worldwide.
      Sensitive, non-invasive diagnostic screen methods are urgently needed to improve
      its survival rates. Stable circulating microRNA offers unique opportunities for
      the early diagnosis of several diseases, including cancers. Our aim has been to
      find new plasma miRNAs that can be used as biomarkers for the detection of CRC.
      METHODOLOGY/PRINCIPAL FINDINGS: According to the results of miRNA profiling
      performed on pooling plasma samples form 10 CRC patients or 10 healthy controls,
      a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188
      3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa
      let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large
      scale validation by qRT-PCR performed on another 191 independent individuals (90
      CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels
      of plasma miR-601 and miR-760 were significantly decreased in colorectal
      neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC
      curve analysis showed that plasma miR-601 and miR-760 were of significant
      diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC
      of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from
      normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1%
      specificity in discriminating advanced adenomas from normal controls.
      CONCLUSIONS/SIGNIFICANCE: Plasma miR-601 and miR-760 can potentially serve as
      promising non-invasive biomarkers for the early detection of CRC.

PMID- 22970210
TI  - Genomic DNA copy-number alterations of the let-7 family in human cancers.
AB  - In human cancer, expression of the let-7 family is significantly reduced, and
      this is associated with shorter survival times in patients. However, the
      mechanisms leading to let-7 downregulation in cancer are still largely unclear.
      Since an alteration in copy-number is one of the causes of gene deregulation in
      cancer, we examined copy number alterations of the let-7 family in 2,969 cancer
      specimens from a high-resolution SNP array dataset. We found that there was a
      reduction in the copy number of let-7 genes in a cancer-type specific manner.
      Importantly, focal deletion of four let-7 family members was found in three
      cancer types: medulloblastoma (let-7a-2 and let-7e), breast cancer (let-7a-2),
      and ovarian cancer (let-7a-3/let-7b). For example, the genomic locus harboring
      let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients.
      We also found a positive correlation between the copy number of let-7b and mature
      let-7b expression in ovarian cancer. Finally, we showed that restoration of let
      7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our
      results indicate that copy number deletion is an important mechanism leading to
      the downregulation of expression of specific let-7 family members in
      medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in
      tumor cells could provide a novel therapeutic strategy for the treatment of
      cancer.

PMID- 22970211
TI  - Monitoring CSF proteome alterations in amyotrophic lateral sclerosis: obstacles
      and perspectives in translating a novel marker panel to the clinic.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder of the motor
      neuron system with poor prognosis and marginal therapeutic options. Current
      clinical diagnostic criteria are based on electrophysiological examination and
      exclusion of other ALS-mimicking conditions. Neuroprotective treatments are,
      however, most promising in early disease stages. Identification of disease
      specific CSF biomarkers and associated biochemical pathways is therefore most
      relevant to monitor disease progression, response to neuroprotective agents and
      to enable early inclusion of patients into clinical trials. METHODS AND FINDINGS:
      CSF from 35 patients with ALS diagnosed according to the revised El Escorial
      criteria and 23 age-matched controls was processed using paramagnetic bead
      chromatography for protein isolation and subsequently analyzed by MALDI-TOF mass
      spectrometry. CSF protein profiles were integrated into a Random Forest model
      constructed from 153 mass peaks. After reducing this peak set to the top 25%, a
      classifier was built which enabled prediction of ALS with high accuracy,
      sensitivity and specificity. Further analysis of the identified peptides resulted
      in a panel of five highly sensitive ALS biomarkers. Upregulation of secreted
      phosphoprotein 1 in ALS-CSF samples was confirmed by univariate analysis of ELISA
      and mass spectrometry data. Further quantitative validation of the five
      biomarkers was achieved in an 80-plex Multiple Reaction Monitoring mass
      spectrometry assay. CONCLUSIONS: ALS classification based on the CSF biomarker
      panel proposed in this study could become a valuable predictive tool for early
      clinical risk stratification. Of the numerous CSF proteins identified, many have
      putative roles in ALS-related metabolic processes, particularly in chromogranin
      mediated secretion signaling pathways. While a stand-alone clinical application
      of this classifier will only be possible after further validation and a
      multicenter trial, it could be readily used to complement current ALS diagnostics
      and might also provide new insights into the pathomechanisms of this disease in
      the future.

PMID- 22970212
TI  - Are plasma biomarkers of immune activation predictive of HIV progression: a
      longitudinal comparison and analyses in HIV-1 and HIV-2 infections?
AB  - BACKGROUND: Chronic immune activation is a hallmark of HIV infection and has been
      associated with disease progression. Assessment of soluble biomarkers indicating
      immune activation provide clues into pathogenesis and hold promise for the
      development of point-of-care monitoring of HIV in resource-poor-settings. Their
      evaluation in cohort resources is therefore needed to further their development
      and use in HIV research. METHODOLOGY/PRINCIPAL FINDINGS: Longitudinal evaluation
      of betaeta-2 microglobulin (beta-2 m), neopterin and suPAR soluble urokinase-type
      plasminogen activator receptor (suPAR) was performed with archived plasma samples
      to predict disease progression and provided the first direct comparison of levels
      in HIV-1 and HIV-2 infections. At least 2095 samples from 137 HIV-1 and 198 HIV-2
      subjects with starting CD4% of >= 28 and median follow up of 4 years were
      analysed. All biomarkers were correlated negatively to CD4% and positively to
      viral load and to each other. Analyses in subjects living for >= 5 years revealed
      increases in median beta-2 m and neopterin and decreases in CD4% over this period
      and the odds of death within 5 years were positively associated with baseline
      levels of beta-2 m and neopterin. ROC analyses strengthened the evidence of
      elevation of biomarkers in patients approaching death in both HIV-1 and HIV-2
      infections. Regression models showed that rates of biomarker fold change
      accelerated from 6-8 years before death with no significant differences between
      biomarker levels in HIV-1 and HIV-2 at equal time points prior to death.An
      'immune activation index' analysis indicative of biomarker levels at equivalent
      viral loads also showed no differences between the two infections.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that beta-2 m and neopterin are
      useful tools for disease monitoring in both HIV-1 and HIV-2 infections, whereas
      sUPAR performed less well. Levels of immune activation per amount of virus were
      comparable in HIV-1 and HIV-2 infected subjects.

PMID- 22970213
TI  - Determination of reference microRNAs for relative quantification in porcine
      tissues.
AB  - Relative quantification is the strategy of choice for processing RT-qPCR data in
      microRNAs (miRNAs) expression studies. Normalisation of relative quantification
      data is performed by using reference genes. In livestock species, such as pigs,
      the determination of reference miRNAs and the optimal number of them has not been
      widely studied. In this study, the stability of ten miRNAs (Ssc-let-7a, Ssc-miR
      103, Ssc-miR-17-3p, Hsa-miR-25, Hsa-miR-93, Ssc-miR-106a, Ssc-miR-191, Ssc-miR
      16, Ssc-miR-26a and Ssc-miR-17-5p) was investigated by RT-qPCR in different
      tissues (skeletal muscle, kidney, liver, ovary and uterus) and in different pig
      breeds (Iberian, Landrace, Large White, Meishan and Vietnamese) as variation
      factors. Stability values were calculated with geNorm and NormFinder algorithms
      obtaining high correlation between them (r(2) = 0.99). The analyses showed that
      tissue is an important variability factor in miRNAs expression stability whereas
      breed is not a determinant factor. All ten miRNAs analysed had good stability
      values and, therefore, can be used as reference miRNAs. When all tissues were
      considered, miR-93 was the most stable miRNA. Dividing data set by tissues, let
      7a was the most stable in skeletal muscle and ovary, miR-17-5p in kidney, miR-26a
      in liver and miR-103 in uterus. Moreover, the optimal number of reference miRNAs
      to be used for proper normalisation data was determined. It is suggested the use
      of five reference miRNAs (miR-93, miR-25, miR-106a, miR-17-5p and miR-26a) in
      multi-tissue experimental designs and the use of three reference miRNAs as the
      optimal number in single tissues studies (let-7a, miR-17-5p and miR-25 in
      skeletal muscle; miR-17-5p, miR-93 and miR-26a in kidney, miR-26a, miR-103 and
      let-7a in liver, let-7a, miR-25 and miR-106a in ovary and miR-103, let-7a and miR
      93 in uterus). Overall, this study provides valuable information about the
      porcine reference miRNAs that can be used in order to perform a proper
      normalisation when relative quantification by RT-qPCR studies is undertaken.

PMID- 22970214
TI  - Cognitive dysfunction among HIV positive and HIV negative patients with psychosis
      in Uganda.
AB  - BACKGROUND: Cognitive impairment is an established phenomenon in HIV infected
      individuals and patients that have psychosis. However there is need to establish
      the severity of the impairment if patients are co morbid with both conditions.
      AIM: To compare cognitive function among HIV positive individuals and HIV
      negative individuals with psychosis. METHODS: We recruited patients with
      psychosis at two national referral hospitals. A standardized demographics
      questionnaire and psychiatric, physical, and laboratory assessments were
      conducted. Types of psychosis were diagnosed using the Mini International
      Neuropsychiatric Inventory-PLUS while cognitive functioning was determined using
      the Mini mental state examination (MMSE) and a neuropsychological test battery.
      Follow-up assessments on cognitive function and severity of psychiatric illness
      were performed at 3 and 6 months. Pairwise comparison and multivariable logistic
      regression analysis were used to determine the differences between the HIV
      positive and HIV negative individuals. RESULTS: There were 156 HIV positive and
      322 HIV negative participants. The mean age was 33 years for the HIV positive
      group and 29 years for the HIV negative group (p<0.001). The HIV positive
      individuals were almost three times (OR = 2.62 CI 95% 1.69-4.06) more likely to
      be cognitively impaired on the MMSE as well as the following cognitive tests:-
      WHO-UCLA Auditory Verbal Learning Test (OR 1.79, 95% CI 1.09-2.92), Verbal
      Fluency (OR 3.42, 95% CI 2.24-5.24), Color Trails 1 (OR 2.03, 95% CI 1.29-3.02)
      and Color Trails 2 (OR 3.50 95% 2.00-6.10) all p = 0.01. There was improvement in
      cognitive function at follow up; however the impairment remained higher for the
      HIV positive group (p<0.001). CONCLUSION: Cognitive impairment in psychosis was
      worsened by HIV infection. Care plans to minimize the effect of this impairment
      should be structured for the management of individuals with HIV and psychosis.

PMID- 22970215
TI  - Understanding barriers to routine HIV screening: knowledge, attitudes, and
      practices of healthcare providers in King County, Washington.
AB  - OBJECTIVE: In 2006, the Centers for Disease Control and Prevention (CDC)
      recommended routine HIV screening in healthcare settings for persons between 13
      and 64 years old. In 2010, the Washington Administrative Code (WAC) was changed
      to align testing rules with these recommendations. We designed this survey to
      ascertain the current state of HIV testing and barriers to routine screening in
      King County, Washington. METHODS: Between March 23 and April 16, 2010, a
      convenience sample of healthcare providers completed an online survey. Providers
      answered true-false and multiple choice questions about national recommendations
      and the WAC, policies in their primary clinical settings, and their personal HIV
      testing practices. Providers were asked to agree or disagree whether commonly
      reported barriers limited their implementation of routine HIV screening. RESULTS:
      Although 76% of the 221 respondents knew that the CDC recommended routine HIV
      screening for persons regardless of their risk, 99 (45%) providers reported that
      their primary clinical setting had a policy to target testing based on patient
      risk factors. Forty-four (20%) providers reported that their primary clinical
      setting had a policy of routine HIV screening, 54 (25%) reported no official
      policy, and 15 (7%) did not know whether a policy existed. Only 11 (5%) providers
      offer HIV testing to all patients at initial visits. When asked about barriers to
      routine screening, 57% of providers agreed that perception that their patient
      population is low risk limits the number of HIV tests they perform. Only 26 (13%)
      providers agreed that concern about reimbursement posed a barrier to testing.
      CONCLUSIONS: Most providers participating in this survey continue to target HIV
      testing, despite knowledge of national recommendations. Efforts are still needed
      to educate providers and policymakers, clarify the recent WAC revisions, and
      implement structural changes in order to increase HIV testing in Washington
      State.

PMID- 22970216
TI  - Evaluation of EMLA cream for preventing pain during tattooing of rabbits: changes
      in physiological, behavioural and facial expression responses.
AB  - BACKGROUND: Ear tattooing is a routine procedure performed on laboratory,
      commercial and companion rabbits for the purpose of identification. Although this
      procedure is potentially painful, it is usually performed without the provision
      of analgesia, so compromising animal welfare. Furthermore, current means to
      assess pain in rabbits are poor and more reliable methods are required. The
      objectives of this study were to assess the physiological and behavioural effects
      of ear tattooing on rabbits, evaluate the analgesic efficacy of topical local
      anaesthetic cream application prior to this procedure, and to develop a scale to
      assess pain in rabbits based on changes in facial expression.
      METHODOLOGY/PRINCIPAL FINDINGS: In a crossover study, eight New Zealand White
      rabbits each underwent four different treatments of actual or sham ear tattooing,
      with and without prior application of a topical local anaesthetic
      (lidocaine/prilocaine). Changes in immediate behaviour, heart rate, arterial
      blood pressure, serum corticosterone concentrations, facial expression and home
      pen behaviours were assessed. Changes in facial expression were examined to
      develop the Rabbit Grimace Scale in order to assess acute pain. Tattooing without
      EMLA cream resulted in significantly greater struggling behaviour and
      vocalisation, greater facial expression scores of pain, higher peak heart rate,
      as well as higher systolic and mean arterial blood pressure compared to all other
      treatments. Physiological and behavioural changes following tattooing with EMLA
      cream were similar to those in animals receiving sham tattoos with or without
      EMLA cream. Behavioural changes 1 hour post-treatment were minimal with no pain
      behaviours identifiable in any group. Serum corticosterone responses did not
      differ between sham and tattoo treatments. CONCLUSIONS: Ear tattooing causes
      transient and potentially severe pain in rabbits, which is almost completely
      prevented by prior application of local anaesthetic cream. The Rabbit Grimace
      Scale developed appears to be a reliable and accurate way to assess acute pain in
      rabbits.

PMID- 22970217
TI  - Increased RhoA prenylation in the loechrig (loe) mutant leads to progressive
      neurodegeneration.
AB  - The Drosophila mutant loechrig (loe) shows age-dependent degeneration of the
      nervous system and is caused by the loss of a neuronal isoform of the AMP
      activated protein kinase (AMPK) gamma-subunit (also known as SNF4Agamma). The
      trimeric AMPK complex is activated by low energy levels and metabolic insults and
      regulates multiple important signal pathways that control cell metabolism. A well
      known downstream target of AMPK is hydroxyl-methylglutaryl-CoA reductase (HMGR),
      a key enzyme in isoprenoid synthesis, and we have previously shown that HMGR
      genetically interacts with loe and affects the severity of the degenerative
      phenotype. Prenylation of proteins like small G-proteins is an important
      posttranslational modification providing lipid moieties that allow the
      association of these proteins with membranes, thereby facilitating their
      subsequent activation. Rho proteins have been extensively studied in neuronal
      outgrowth, however, much less is known about their function in neuronal
      maintenance. Here we show that the loe mutation interferes with isoprenoid
      synthesis, leading to increased prenylation of the small GTPase Rho1, the fly
      orthologue of vertebrate RhoA. We also demonstrate that increased prenylation and
      Rho1 activity causes neurodegeneration and aggravates the behavioral and
      degenerative phenotypes of loe. Because we cannot detect defects in the
      development of the central nervous system in loe, this suggests that loe only
      interferes with the function of the RhoA pathway in maintaining neuronal
      integrity during adulthood. In addition, our results show that alterations in
      isoprenoids can result in progressive neurodegeneration, supporting findings in
      vertebrates that prenylation may play a role in neurodegenerative diseases like
      Alzheimer's Disease.

PMID- 22970218
TI  - Is universal HBV vaccination of healthcare workers a relevant strategy in
      developing endemic countries? The case of a university hospital in Niger.
AB  - BACKGROUND: Exposure to hepatitis B virus (HBV) remains a serious risk to
      healthcare workers (HCWs) in endemic developing countries owing to the strong
      prevalence of HBV in the general and hospital populations, and to the high rate
      of occupational blood exposure. Routine HBV vaccination programs targeted to high
      risk groups and especially to HCWs are generally considered as a key element of
      prevention strategies. However, the high rate of natural immunization among
      adults in such countries where most infections occur perinatally or during early
      childhood must be taken into account. METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a cross sectional study in 207 personnel of 4 occupational groups
      (medical, paramedical, cleaning staff, and administrative) in Niamey's National
      Hospital, Niger, in order to assess the prevalence of HBV markers, to evaluate
      susceptibility to HBV infection, and to identify personnel who might benefit from
      vaccination. The proportion of those who declared a history of occupational blood
      exposure ranged from 18.9% in the administrative staff to 46.9% in paramedical
      staff. Only 7.2% had a history of vaccination against HBV with at least 3
      injections. Ninety two percent were anti-HBc positive. When we focused on170
      HCWs, only 12 (7.1%) showed no biological HBV contact. Twenty six were HBsAg
      positive (15,3%; 95% confidence interval: 9.9%-20.7%) of whom 8 (32%) had a viral
      load >2000 IU/ml. CONCLUSIONS/SIGNIFICANCE: The very small proportion of HCWs
      susceptible to HBV infection in our study and other studies suggests that in a
      global approach to prevent occupational infection by bloodborne pathogens, a
      universal hepatitis B vaccination of HCWs is not priority in these settings. The
      greatest impact on the risk will most likely be achieved by focusing efforts on
      primary prevention strategies to reduce occupational blood exposure. HBV
      screening in HCWs and treatment of those with chronic HBV infection should be
      however considered.

PMID- 22970219
TI  - Diversity and complexity in chromatin recognition by TFII-I transcription factors
      in pluripotent embryonic stem cells and embryonic tissues.
AB  - GTF2I and GTF2IRD1 encode a family of closely related transcription factors TFII
      I and BEN critical in embryonic development. Both genes are deleted in Williams
      Beuren syndrome, a complex genetic disorder associated with neurocognitive,
      craniofacial, dental and skeletal abnormalities. Although genome-wide promoter
      analysis has revealed the existence of multiple TFII-I binding sites in embryonic
      stem cells (ESCs), there was no correlation between TFII-I occupancy and gene
      expression. Surprisingly, TFII-I recognizes the promoter sequences enriched for
      H3K4me3/K27me3 bivalent domain, an epigenetic signature of developmentally
      important genes. Moreover, we discovered significant differences in the
      association between TFII-I and BEN with the cis-regulatory elements in ESCs and
      embryonic craniofacial tissues. Our data indicate that in embryonic tissues BEN,
      but not the highly homologous TFII-I, is primarily recruited to target gene
      promoters. We propose a "feed-forward model" of gene regulation to explain the
      specificity of promoter recognition by TFII-I factors in eukaryotic cells.

PMID- 22970220
TI  - Influence of acute exposure to high altitude on basal and postprandial plasma
      levels of gastroenteropancreatic peptides.
AB  - Acute mountain sickness (AMS) is characterized by headache often accompanied by
      gastrointestinal complaints that vary from anorexia through nausea to vomiting.
      The aim of this study was to investigate the influence of high altitude on plasma
      levels of gastroenteropancreatic (GEP) peptides and their association to AMS
      symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11
      subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m
      (Jungfraujoch, Switzerland), over the course of three days. In a second study (n
      = 5), the same peptides and ghrelin were measured in subjects who consumed
      standardized liquid meals at these two elevations. AMS symptoms and oxygen
      saturation were monitored. In the first study, both fasting (morning 8 a.m.) and
      stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and
      cholecystokinin (CCK) were significantly lower at high altitude as compared to
      baseline, whereas gastrin and motilin concentrations were significantly
      increased. Fasting plasma neurotensin was significantly enhanced whereas
      stimulated levels were reduced. Both fasting and stimulated plasma motilin levels
      correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r =
      0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at
      high altitude. In the second study, meal-stimulated integrated (= area under
      curve) plasma CCK, PP, and neurotensin values were significantly suppressed at
      high altitude, whereas integrated levels of gastrin were increased and integrated
      VIP and ghrelin levels were unchanged. In summary, our data show that acute
      exposure to a hypobaric hypoxic environment causes significant changes in fasting
      and stimulated plasma levels of GEP peptides over consecutive days and after a
      standardized meal. The changes of peptide levels were not uniform. Based on the
      inhibition of PP and neurotensin release a reduction of the cholinergic tone can
      be postulated.

PMID- 22970221
TI  - Characterization of genes encoding for acquired bacitracin resistance in
      Clostridium perfringens.
AB  - Phenotypic bacitracin resistance has been reported in Clostridium perfringens.
      However, the genes responsible for the resistance have not yet been
      characterized. Ninety-nine C. perfringens isolates recovered from broilers and
      turkeys were tested for phenotypic bacitracin resistance. Bacitracin MIC(90)
      (>256 ug/ml) was identical for both turkey and chicken isolates; whereas MIC(50)
      was higher in turkey isolates (6 ug/ml) than in chicken isolates (3 ug/ml).
      Twenty-four of the 99 isolates showed high-level bacitracin resistance (MIC
      breakpoint >256 ug/ml) and the genes encoding for this resistance were
      characterized in C. perfringens c1261_A strain using primer walking. Sequence
      analysis and percentages of amino acid identity revealed putative genes encoding
      for both an ABC transporter and an overproduced undecaprenol kinase in C.
      perfringens c1261_A strain. These two mechanisms were shown to be both encoded by
      the putative bcrABD operon under the control of a regulatory gene, bcrR. Efflux
      pump inhibitor thioridazine was shown to increase significantly the
      susceptibility of strain c1261_A to bacitracin. Upstream and downstream from the
      bcr cluster was an IS1216-like element, which may play a role in the
      dissemination of this resistance determinant. Pulsed-field gel electrophoresis
      with prior double digestion with I-CeuI/MluI enzymes followed by hybridization
      analyses revealed that the bacitracin resistance genes bcrABDR were located on
      the chromosome. Semi-quantitative RT-PCR demonstrated that this gene cluster is
      expressed under bacitracin stress. Microarray analysis revealed the presence of
      these genes in all bacitracin resistant strains. This study reports the discovery
      of genes encoding for a putative ABC transporter and an overproduced undecaprenol
      kinase associated with high-level bacitracin resistance in C. perfringens
      isolates from turkeys and broiler chickens.

PMID- 22970222
TI  - Rag1-/- mutant zebrafish demonstrate specific protection following bacterial re
      exposure.
AB  - BACKGROUND: Recombination activation gene 1 deficient (rag1(-/-)) mutant
      zebrafish have a reduced lymphocyte-like cell population that lacks functional B
      and T lymphocytes of the acquired immune system, but includes Natural Killer (NK)
      like cells and Non-specific cytotoxic cells (NCC) of the innate immune system.
      The innate immune system is thought to lack the adaptive characteristics of an
      acquired immune system that provide enhanced protection to a second exposure of
      the same pathogen. It has been shown that NK cells have the ability to mediate
      adaptive immunity to chemical haptens and cytomegalovirus in murine models. In
      this study we evaluated the ability of rag1(-/-) mutant zebrafish to mount a
      protective response to the facultative intracellular fish bacterium Edwardsiella
      ictaluri. METHODOLOGY/PRINCIPAL FINDINGS: Following secondary challenge with a
      lethal dose of homologous bacteria 4 and 8 weeks after a primary vaccination,
      rag1(-/-) mutant zebrafish demonstrated protective immunity. Heterologous
      bacterial exposures did not provide protection. Adoptive leukocyte transfers from
      previously exposed mutants conferred protective immunity to naive mutants when
      exposed to homologous bacteria. CONCLUSIONS/SIGNIFICANCE: Our findings show that
      a component of the innate immune system mounted a response that provided
      significantly increased survival when rag1(-/-) mutant zebrafish were re-exposed
      to the same bacteria. Further, adoptive cell transfers demonstrated that kidney
      interstitial leukocytes from previously exposed rag1(-/-) mutant zebrafish
      transferred this protective immunity. This is the first report of any rag1(-/-)
      mutant vertebrate mounting a protective secondary immune response to a bacterial
      pathogen, and demonstrates that a type of zebrafish innate immune cell can
      mediate adaptive immunity in the absence of T and B cells.

PMID- 22970223
TI  - The B. subtilis MgtE magnesium transporter can functionally compensate TRPM7
      deficiency in vertebrate B-cells.
AB  - Recent studies have shown that the vertebrate magnesium transporters Solute
      carrier family 41, members 1 and 2 (SLC41A1, SLC41A2) and Magnesium transporter
      subtype 1 (MagT1) can endow vertebrate B-cells lacking the ion-channel kinase
      Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) with a
      capacity to grow and proliferate. SLC41A1 and SLC41A2 display distant homology to
      the prokaryotic family of Mg(2+) transporters, MgtE, first characterized in
      Bacillus subtilis. These sequence similarities prompted us to investigate whether
      MgtE could potentially compensate for the lack of TRPM7 in the vertebrate TRPM7
      deficient DT40 B-cell model system. Here, we report that overexpression of MgtE
      is able to rescue the growth of TRPM7-KO DT40 B-cells. However, contrary to a
      previous report that describes regulation of MgtE channel gating by Mg(2+) in a
      bacterial spheroplast model system, whole cell patch clamp analysis revealed no
      detectable current development in TRPM7-deficient cells expressing MgtE. In
      addition, we observed that MgtE expression is strongly downregulated at high
      magnesium concentrations, similar to what has been described for its vertebrate
      homolog, SLC41A1. We also show that the N-terminal cytoplasmic domain of MgtE is
      required for normal MgtE channel function, functionally confirming the predicted
      importance of this domain in regulation of MgtE-mediated Mg(2+) entry. Overall,
      our findings show that consistent with its proposed function, Mg(2+) uptake
      mediated by MgtE is able to restore cell growth and proliferation of TRPM7
      deficient cells and supports the concept of functional homology between MgtE and
      its vertebrate homologs.

PMID- 22970224
TI  - Inflammation, coagulation and cardiovascular disease in HIV-infected individuals.
AB  - BACKGROUND: The SMART study was a trial of intermittent use of antiretroviral
      therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral
      suppression [VS]) as a strategy to reduce toxicities, including cardiovascular
      disease (CVD) risk. We studied the predictive value of high sensitivity C
      reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and
      mortality in HIV-infected patients who were enrolled in SMART beyond other
      measured CVD risk factors. METHODS: A blood sample was available in 5098
      participants who were enrolled in the SMART study for the measurement of IL-6,
      hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated
      for each quartile (Q) for each biomarker vs the 1(st) quartile and for 1 SD
      higher levels. For both treatment groups combined, unadjusted and adjusted HRs
      were determined using Cox regression models. RESULTS: There were 252 participants
      who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI)
      for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38,
      3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for
      the DC and VS treatment groups (interaction p-values were >0.30). The addition of
      the three biomarkers to a model that included baseline covariates significantly
      improved model fit (p<0.001). Area under the curve (AUC) estimates improved with
      inclusion of the three biomarkers in a model that included baseline covariates
      corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001
      for difference). CONCLUSIONS: In HIV-infected individuals, IL-6, hsCRP and D
      dimer are associated with an increased risk of CVD independent of other CVD risk
      factors. Further research is needed to determine whether these biomarkers can be
      used to improve CVD risk prediction among HIV positive individuals.

PMID- 22970225
TI  - My neighbor: children's perception of agency in interaction with an imaginary
      agent.
AB  - Children may treat an invisible entity as a live and thinking entity, known as an
      imaginary companion (IC). Some researchers suggest that this is simply pretend
      play, but it is possible that children experience agency in their interactions
      with ICs. Given the literature on cognitive science and social brain research, we
      hypothesize that young children may have an agent-perception system that responds
      to an invisible agent by which they may experience realistic agency in their
      interactions with ICs. In this study, children were introduced to an invisible
      agent and an invisible stone. However, they assigned biological and psychological
      properties to the agent but not the stone. The tendency of assigning such
      properties was stronger in children with ICs than in those without ICs. These
      results contribute to our understanding of cognitive and neural development in
      typical and atypical children.

PMID- 22970226
TI  - Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized
      mouse model in vivo.
AB  - Despite insights into the molecular pathways regulating hypoxia-induced gene
      expression, it is not known which cell types accomplish oxygen sensing during neo
      vasculogenesis. We have developed a humanized mouse model of endothelial and
      mesenchymal progenitor co-transplantation to delineate the cellular compartments
      responsible for hypoxia response during vasculogenesis. Mesenchymal
      stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription
      factor (HIF)-1alpha earlier and more sensitively than endothelial colony forming
      progenitor cells (ECFCs) in vitro and in vivo. Hypoxic ECFCs showed reduced
      function in vitro and underwent apoptosis within 24h in vivo when used without
      MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF
      1alpha abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs
      could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting
      in the formation of patent perfused human vessels. Several angiogenic factors
      need to act in concert to partially substitute mesenchymal HIF-deficiency.
      Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to
      initiate vasculogenesis in vivo and to bypass hypoxia-induced apoptosis. We
      describe a novel mechanistic role of MSPCs as oxygen sensors promoting
      vasculogenesis thus underscoring their importance for the development of advanced
      cellular therapies.

PMID- 22970228
TI  - Technical reproducibility of genotyping SNP arrays used in genome-wide
      association studies.
AB  - During the last several years, high-density genotyping SNP arrays have
      facilitated genome-wide association studies (GWAS) that successfully identified
      common genetic variants associated with a variety of phenotypes. However, each of
      the identified genetic variants only explains a very small fraction of the
      underlying genetic contribution to the studied phenotypic trait. Moreover,
      discordance observed in results between independent GWAS indicates the potential
      for Type I and II errors. High reliability of genotyping technology is needed to
      have confidence in using SNP data and interpreting GWAS results. Therefore,
      reproducibility of two widely genotyping technology platforms from Affymetrix and
      Illumina was assessed by analyzing four technical replicates from each of the six
      individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within
      a laboratory for the sample platform, 98.59% to 99.86% across laboratories for
      the same platform, and 98.80% across genotyping platforms was observed. Moreover,
      arrays with low quality data were detected when comparing genotyping data from
      technical replicates, but they could not be detected according to venders'
      quality control (QC) suggestions. Our results demonstrated the technical
      reliability of currently available genotyping platforms but also indicated the
      importance of incorporating some technical replicates for genotyping QC in order
      to improve the reliability of GWAS results. The impact of discordant genotypes on
      association analysis results was simulated and could explain, at least in part,
      the irreproducibility of some GWAS findings when the effect size (i.e. the odds
      ratio) and the minor allele frequencies are low.

PMID- 22970227
TI  - Recognizing biological motion and emotions from point-light displays in autism
      spectrum disorders.
AB  - One of the main characteristics of Autism Spectrum Disorder (ASD) are problems
      with social interaction and communication. Here, we explored ASD-related
      alterations in 'reading' body language of other humans. Accuracy and reaction
      times were assessed from two observational tasks involving the recognition of
      'biological motion' and 'emotions' from point-light displays (PLDs). Eye
      movements were recorded during the completion of the tests. Results indicated
      that typically developed-participants were more accurate than ASD-subjects in
      recognizing biological motion or emotions from PLDs. No accuracy differences were
      revealed on two control-tasks (involving the indication of color-changes in the
      moving point-lights). Group differences in reaction times existed on all tasks,
      but effect sizes were higher for the biological and emotion recognition tasks.
      Biological motion recognition abilities were related to a person's ability to
      recognize emotions from PLDs. However, ASD-related atypicalities in emotion
      recognition could not entirely be attributed to more basic deficits in biological
      motion recognition, suggesting an additional ASD-specific deficit in recognizing
      the emotional dimension of the point light displays. Eye movements were assessed
      during the completion of tasks and results indicated that ASD-participants
      generally produced more saccades and shorter fixation-durations compared to the
      control-group. However, especially for emotion recognition, these altered eye
      movements were associated with reductions in task-performance.

PMID- 22970230
TI  - Quantifying the effect of polymer blending through molecular modelling of
      cyanurate polymers.
AB  - Modification of polymer properties by blending is a common practice in the
      polymer industry. We report here a study of blends of cyanurate polymers by
      molecular modelling that shows that the final experimentally determined
      properties can be predicted from first principles modelling to a good degree of
      accuracy. There is always a compromise between simulation length, accuracy and
      speed of prediction. A comparison of simulation times shows that 125ps of
      molecular dynamics simulation at each temperature provides the optimum compromise
      for models of this size with current technology. This study opens up the
      possibility of computer aided design of polymer blends with desired physical and
      mechanical properties.

PMID- 22970229
TI  - Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and
      lowering pressure overload in rats with pulmonary arterial hypertension.
AB  - BACKGROUND: Most of the deaths among patients with severe pulmonary arterial
      hypertension (PAH) are caused by progressive right ventricular (RV) pathological
      remodeling, dysfunction, and failure. Nicorandil can inhibit the development of
      PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether
      nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling
      has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in
      rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure
      (RVSP) was measured at the end of each week after MCT injection. Blood samples
      were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were
      excised for histopathological, ultrastructural, immunohistochemical, and Western
      blotting analyses. The MCT-injected rats exhibited greater mortality and less
      weight gain and showed significantly increased RVSP and RV hypertrophy during the
      second week. These worsened during the third week. MCT injection for three weeks
      caused pathological RV remodeling, characterized by hypertrophy, fibrosis,
      dysfunction, and RV mitochondrial impairment, as indicated by increased levels of
      apoptosis. Nicorandil improved survival, weight gain, and RV function,
      ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH
      rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a
      concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these
      beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE:
      Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV
      pressure overload but also by inhibiting apoptosis in cardiomyocytes through the
      activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. The use of
      a mitoK(ATP) channel opener such as nicorandil for PAH-associated RV remodeling
      and dysfunction may represent a new therapeutic strategy for the amelioration of
      RV remodeling during the early stages of PAH.

PMID- 22970231
TI  - Dietary monounsaturated fatty acids intake and risk of skin photoaging.
AB  - BACKGROUND: Intake of monounsaturated fatty acids has been reported to reduce
      oxidative stress, insulin resistance and related inflammatory processes and may
      thus protect from skin photoaging. The objective of this study was to investigate
      the association between the risk of photoaging, monounsaturated fatty acids
      intake and the sources of monounsaturated fatty acids. METHODOLOGY/PRINCIPAL
      FINDINGS: A cross sectional study was conducted within the framework of the
      SUVIMAX cohort. The survey included 1264 women and 1655 men aged between 45 and
      60 years old. Dietary monounsaturated fatty acids intakes were estimated by
      dietary source through at least ten 24-h diet records completed during the first
      2.5 years of the follow-up period. Severity of facial skin photoaging was graded
      by trained investigators at baseline during a clinical examination using a 6
      grade scale illustrated by photographs. A lower risk of severe photoaging was
      associated with higher intakes of monounsaturated fatty acids from olive oil in
      both sexes. Strikingly, no association was found with intake of monounsaturated
      fatty acids from animal sources whether from dairy products, meat or processed
      meat. CONCLUSION/SIGNIFICANCE: These findings support the beneficial effect of
      dietary olive oil or healthy diet habits associated with olive oil consumption on
      the severity of facial photoaging.

PMID- 22970232
TI  - Protein disulfide isomerase-like protein 1-1 controls endosperm development
      through regulation of the amount and composition of seed proteins in rice.
AB  - Protein disulfide isomerase (PDI) is a chaperone protein involved in oxidative
      protein folding by acting as a catalyst and assisting folding in the endoplasmic
      reticulum (ER). A genome database search showed that rice contains 19 PDI-like
      genes. However, their functions are not clearly identified. This paper shows
      possible functions of rice PDI-like protein 1-1 (PDIL1-1) during seed
      development. Seeds of the T-DNA insertion PDIL1-1 mutant, PDIL1-1Delta,
      identified by genomic DNA PCR and western blot analysis, display a chalky
      phenotype and a thick aleurone layer. Protein content per seed was significantly
      lower and free sugar content higher in PDIL1-1Delta mutant seeds than in the wild
      type. Proteomic analysis of PDIL1-1Delta mutant seeds showed that PDIL1-1 is post
      translationally regulated, and its loss causes accumulation of many types of seed
      proteins including glucose/starch metabolism- and ROS (reactive oxygen species)
      scavenging-related proteins. In addition, PDIL1-1 strongly interacts with the
      cysteine protease OsCP1. Our data indicate that the opaque phenotype of PDIL1
      1Delta mutant seeds results from production of irregular starch granules and
      protein body through loss of regulatory activity for various proteins involved in
      the synthesis of seed components.

PMID- 22970233
TI  - Elevational patterns in archaeal diversity on Mt. Fuji.
AB  - Little is known of how archaeal diversity and community ecology behaves along
      elevational gradients. We chose to study Mount Fuji of Japan as a geologically
      and topographically uniform mountain system, with a wide range of elevational
      zones. PCR-amplified soil DNA for the archaeal 16 S rRNA gene was pyrosequenced
      and taxonomically classified against EzTaxon-e archaeal database. At a bootstrap
      cut-off of 80%, most of the archaeal sequences were classified into phylum
      Thaumarchaeota (96%) and Euryarchaeota (3.9%), with no sequences classified into
      other phyla. Archaeal OTU richness and diversity on Fuji showed a pronounced
      'peak' in the mid-elevations, around 1500 masl, within the boreal forest zone,
      compared to the temperate forest zone below and the alpine fell-field and desert
      zones above. Diversity decreased towards higher elevations followed by a subtle
      increase at the summit, mainly due to an increase in the relative abundance of
      the group I.1b of Thaumarchaeota. Archaeal diversity showed a strong positive
      correlation with soil NH(4)(+), K and NO(3)(-). Archaeal diversity does not
      parallel plant diversity, although it does roughly parallel bacterial diversity.
      Ecological hypotheses to explain the mid diversity bulge on Fuji include
      intermediate disturbance effects, and the result of mid elevations combining a
      mosaic of upper and lower slope environments. Our findings show clearly that
      archaeal soil communities are highly responsive to soil environmental gradients,
      in terms of both their diversity and community composition. Distinct communities
      of archaea specific to each elevational zone suggest that many archaea may be
      quite finely niche-adapted within the range of soil environments. A further
      interesting finding is the presence of a mesophilic component of archaea at high
      altitudes on a mountain that is not volcanically active. This emphasizes the
      importance of microclimate - in this case solar heating of the black volcanic ash
      surface--for the ecology of soil archaea.

PMID- 22970234
TI  - Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes
      hypothalamic-pituitary-adrenal axis inhibition in fetal rats.
AB  - Epidemiological investigations have shown that fetuses with intrauterine growth
      retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical
      investigations and experiments have demonstrated that caffeine is a definite
      inducer of IUGR, as children who ingest caffeine-containing food or drinks are
      highly susceptible to adult obesity and hypertension. Our goals for this study
      were to investigate the effect of prenatal caffeine ingestion on the functional
      development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA)
      axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration
      induced by caffeine. Pregnant Wistar rats were intragastrically administered 20,
      60, and 180 mg/kg . d caffeine from gestational days 11-20. The results show that
      prenatal caffeine ingestion significantly decreased the expression of fetal
      hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed
      into slight and the expression of fetal adrenal steroid acute regulatory protein
      (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level
      of fetal adrenal endogenous corticosterone (CORT), were all significantly
      decreased after caffeine treatment. Moreover, caffeine ingestion significantly
      increased the levels of maternal and fetal blood CORT and decreased the
      expression of placental 11beta-hydroxysteroid dehydrogenase-2 (11beta-HSD-2).
      Additionally, both in vivo and in vitro studies show that caffeine can
      downregulate the expression of fetal hippocampal 11beta-HSD-2, promote the
      expression of 11beta-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor
      (GR), and enhance DNA methylation within the hippocampal 11beta-HSD-2 promoter.
      These results suggest that prenatal caffeine ingestion inhibits the development
      of the fetal HPA axis, which may be associated with the fetal overexposure to
      maternal glucocorticoid and activated glucocorticoid metabolism in the fetal
      hippocampus. These results will be beneficial in elucidating the developmental
      toxicity of caffeine and in exploring the fetal origin of adult HPA axis
      dysfunction and metabolic syndrome susceptibility for offspring with IUGR induced
      by caffeine.

PMID- 22970235
TI  - Human cytomegalovirus induces TLR4 signaling components in monocytes altering
      TIRAP, TRAM and downstream interferon-beta and TNF-alpha expression.
AB  - Using TLR pathways, primary human cytomegalovirus (HCMV) induces innate responses
      including the production of inflammatory cytokines. Mounting evidence suggests
      that LPS recognition by TLR4/MD2/CD14 results in differential utilization of
      TIRAP-TRAF6 and TRAM-TRIF signaling, thereby leading to transcriptional
      activation of various cytokine genes. However, relative roles of the
      TLR4/MD2/CD14 complex and its adaptor proteins TIRAP and TRAM involved in
      regulating monocyte responses to HCMV are incomplete. Here, we provided evidence
      supporting the notion that the TLR4/MD2/CD14 complex contributes notably to HCMV
      induced signaling and subsequent cytokine production in monocytes. In particular,
      induction of both IL-6 and IL-8 is associated with elevated TIRAP and reduced
      TRAM mRNA expression. The latter may serve in a compensatory pathway that yields
      a robust IFN response when TIRAP signaling is blocked in monocytes incubated with
      Toledo strain HCMV. Inhibitory studies using antisense oligonucleotides or
      neutralizing antibodies indicate that IL-6 induction by TLR4/MD2 complex is
      important for the activation of endogenous CD14 which later acts in concert or
      synergy with TLR4/MD2 as a factor resulting in IL-8 gene expression. We further
      show that exogenous recombinant CD14 can potentiate innate immune response via
      TLR4-dependent and possibly via TLR9-dependent pathways to promote enhanced
      expression/production of IL-8 and IFN-beta, respectively.

PMID- 22970236
TI  - Phosphorylation and subcellular localization of p27Kip1 regulated by hydrogen
      peroxide modulation in cancer cells.
AB  - The Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a key protein in the
      decision between proliferation and cell cycle exit. Quiescent cells show nuclear
      p27Kip1, but this protein is exported to the cytoplasm in response to
      proliferating signals. We recently reported that catalase treatment increases the
      levels of p27Kip1 in vitro and in vivo in a murine model. In order to
      characterize and broaden these findings, we evaluated the regulation of p27Kip1
      by hydrogen peroxide (H(2)O(2)) in human melanoma cells and melanocytes. We
      observed a high percentage of p27Kip1 positive nuclei in melanoma cells
      overexpressing or treated with exogenous catalase, while non-treated controls
      showed a cytoplasmic localization of p27Kip1. Then we studied the levels of
      p27Kip1 phosphorylated (p27p) at serine 10 (S10) and at threonine 198 (T198)
      because phosphorylation at these sites enables nuclear exportation of this
      protein, leading to accumulation and stabilization of p27pT198 in the cytoplasm.
      We demonstrated by western blot a decrease in p27pS10 and p27pT198 levels in
      response to H(2)O(2) removal in melanoma cells, associated with nuclear p27Kip1.
      Melanocytes also exhibited nuclear p27Kip1 and lower levels of p27pS10 and
      p27pT198 than melanoma cells, which showed cytoplasmic p27Kip1. We also showed
      that the addition of H(2)O(2) (0.1 uM) to melanoma cells arrested in G1 by serum
      starvation induces proliferation and increases the levels of p27pS10 and p27pT198
      leading to cytoplasmic localization of p27Kip1. Nuclear localization and post
      translational modifications of p27Kip1 were also demonstrated by catalase
      treatment of colorectal carcinoma and neuroblastoma cells, extending our findings
      to these other human cancer types. In conclusion, we showed in the present work
      that H(2)O(2) scavenging prevents nuclear exportation of p27Kip1, allowing cell
      cycle arrest, suggesting that cancer cells take advantage of their intrinsic pro
      oxidant state to favor cytoplasmic localization of p27Kip1.

PMID- 22970237
TI  - Bipartite graphs as models of population structures in evolutionary multiplayer
      games.
AB  - By combining evolutionary game theory and graph theory, "games on graphs" study
      the evolutionary dynamics of frequency-dependent selection in population
      structures modeled as geographical or social networks. Networks are usually
      represented by means of unipartite graphs, and social interactions by two-person
      games such as the famous prisoner's dilemma. Unipartite graphs have also been
      used for modeling interactions going beyond pairwise interactions. In this paper,
      we argue that bipartite graphs are a better alternative to unipartite graphs for
      describing population structures in evolutionary multiplayer games. To illustrate
      this point, we make use of bipartite graphs to investigate, by means of computer
      simulations, the evolution of cooperation under the conventional and the
      distributed N-person prisoner's dilemma. We show that several implicit
      assumptions arising from the standard approach based on unipartite graphs (such
      as the definition of replacement neighborhoods, the intertwining of individual
      and group diversity, and the large overlap of interaction neighborhoods) can have
      a large impact on the resulting evolutionary dynamics. Our work provides a clear
      example of the importance of construction procedures in games on graphs, of the
      suitability of bigraphs and hypergraphs for computational modeling, and of the
      importance of concepts from social network analysis such as centrality,
      centralization and bipartite clustering for the understanding of dynamical
      processes occurring on networked population structures.

PMID- 22970238
TI  - Glacial history of a modern invader: phylogeography and species distribution
      modelling of the Asian tiger mosquito Aedes albopictus.
AB  - BACKGROUND: The tiger mosquito, Aedes albopictus, is one of the 100 most invasive
      species in the world and a vector of human diseases. In the last 30 years, it has
      spread from its native range in East Asia to Africa, Europe, and the Americas.
      Although this modern invasion has been the focus of many studies, the history of
      the species' native populations remains poorly understood. Here, we aimed to
      assess the role of Pleistocene climatic changes in shaping the current
      distribution of the species in its native range. METHODOLOGY/PRINCIPAL FINDINGS:
      We investigated the phylogeography, historical demography, and species
      distribution of Ae. albopictus native populations at the Last Glacial Maximum
      (LGM). Individuals from 16 localities from East Asia were analyzed for sequence
      variation at two mitochondrial genes. No phylogeographic structure was observed
      across the study area. Demographic analyses showed a signature of population
      expansion that started roughly 70,000 years BP. The occurrence of a continuous
      and climatically suitable area comprising Southeast China, Indochinese Peninsula,
      and Sundaland during LGM was indicated by species distribution modelling.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest an evolutionary scenario in which,
      during the last glacial phase, Ae. albopictus did not experience a fragmentation
      phase but rather persisted in interconnected populations and experienced
      demographic growth. The wide ecological flexibility of the species probably
      played a crucial role in its response to glacial-induced environmental changes.
      Currently, there is little information on the impact of Pleistocene climatic
      changes on animal species in East Asia. Most of the studies focused on forest
      associated species and suggested cycles of glacial fragmentation and post-glacial
      expansion. The case of Ae. albopictus, which exhibits a pattern not previously
      observed in the study area, adds an important piece to our understanding of the
      Pleistocene history of East Asian biota.

PMID- 22970239
TI  - Genetic association of the KLK4 locus with risk of prostate cancer.
AB  - The Kallikrein-related peptidase, KLK4, has been shown to be significantly
      overexpressed in prostate tumours in numerous studies and is suggested to be a
      potential biomarker for prostate cancer. KLK4 may also play a role in prostate
      cancer progression through its involvement in epithelial-mesenchymal transition,
      a more aggressive phenotype, and metastases to bone. It is well known that
      genetic variation has the potential to affect gene expression and/or various
      protein characteristics and hence we sought to investigate the possible role of
      single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer.
      Assessment of 61 SNPs in the KLK4 locus (+/- 10 kb) in approximately 1300
      prostate cancer cases and 1300 male controls for associations with prostate
      cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus >= 7)
      revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the
      P(trend)<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and
      the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551
      encodes a non-synonymous serine to alanine substitution at position 22 of the
      long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs,
      rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high
      linkage disequilibrium with each other (r(2) >= 0.98). Our findings provide
      suggestive evidence of a role for genetic variation in the KLK4 locus in prostate
      cancer predisposition.

PMID- 22970240
TI  - Oral inoculation of young dairy calves with Mycoplasma bovis results in
      colonization of tonsils, development of otitis media and local immunity.
AB  - Because M. bovis otitis media is an economically important problem, there is a
      need to understand the pathogenesis of disease, not only to improve our
      understanding of the factors contributing to the development of this disease but
      also to inform the development of improved diagnostic tests and therapy. Oral
      ingestion of M. bovis-contaminated milk is linked, but not definitively proven,
      to development of otitis media. In the current study, we demonstrate that oral
      ingestion of M. bovis infected colostrum can result in an ascending infection and
      development of otitis media. Importantly, M. bovis was found to have a previously
      unrecognized tendency for colonization of the tonsils of calves, which most
      likely contributed to the subsequent development of otitis media. In contrast,
      transtracheal inoculation failed to produce clinically significant upper
      respiratory tract disease, although did induce lower respiratory tract disease.
      The upper respiratory tract was the major site of M. bovis-specific B cell and
      mucosal IgA responses in calves inoculated by the oral route. The oral
      inoculation route of infection presented here is particularly suited to the study
      of host-pathogen interactions during initial colonization of the tonsils,
      expansion of infection and dissemination to the lower respiratory tract and
      middle ear. In addition, it could be used to investigate potential new
      preventative or control strategies, especially those aimed at limiting
      colonization of the tonsils and/or spread to the middle ear.

PMID- 22970241
TI  - Mac-2 binding protein is a novel E-selectin ligand expressed by breast cancer
      cells.
AB  - Hematogenous metastasis involves the adhesion of circulating tumor cells to
      vascular endothelium of the secondary site. We hypothesized that breast cancer
      cell adhesion is mediated by interaction of endothelial E-selectin with its
      glycoprotein counter-receptor(s) expressed on breast cancer cells. At a
      hematogenous wall shear rate, ZR-75-1 breast cancer cells specifically adhered to
      E-selectin expressing human umbilical vein endothelial cells when tested in
      parallel plate flow chamber adhesion assays. Consistent with their E-selectin
      ligand activity, ZR-75-1 cells expressed flow cytometrically detectable epitopes
      of HECA-452 mAb, which recognizes high efficiency E-selectin ligands typified by
      sialofucosylated moieties. Multiple E-selectin reactive proteins expressed by ZR
      75-1 cells were revealed by immunoprecipitation with E-selectin chimera (E-Ig
      chimera) followed by Western blotting. Mass spectrometry analysis of the 72 kDa
      protein, which exhibited the most prominent E-selectin ligand activity,
      corresponded to Mac-2 binding protein (Mac-2BP), a heretofore unidentified E
      selectin ligand. Immunoprecipitated Mac-2BP expressed sialofucosylated epitopes
      and possessed E-selectin ligand activity when tested by Western blot analysis
      using HECA-452 mAb and E-Ig chimera, respectively, demonstrating that Mac-2BP is
      a novel high efficiency E-selectin ligand. Furthermore, silencing the expression
      of Mac-2BP from ZR-75-1 cells by shRNA markedly reduced their adhesion to E
      selectin expressing cells under physiological flow conditions, confirming the
      functional E-selectin ligand activity of Mac-2BP on intact cells. In addition to
      ZR-75-1 cells, several other E-selectin ligand positive breast cancer cell lines
      expressed Mac-2BP as detected by Western blot and flow cytometry, suggesting that
      Mac-2BP may be an E-selectin ligand in a variety of breast cancer types. Further,
      invasive breast carcinoma tissue showed co-localized expression of Mac-2BP and
      HECA-452 antigens by fluorescence microscopy, underscoring the possible role of
      Mac-2BP as an E-selectin ligand. In summary, breast cancer cells express Mac-2BP
      as a novel E-selectin ligand, potentially revealing a new prognostic and
      therapeutic target for breast cancer.

PMID- 22970242
TI  - Vascular dysfunction following polymicrobial sepsis: role of pattern recognition
      receptors.
AB  - AIMS: Aim was to elucidate the specific role of pattern recognition receptors in
      vascular dysfunction during polymicrobial sepsis (colon ascendens stent
      peritonitis, CASP). METHODS AND RESULTS: Vascular contractility of C57BL/6
      (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D,
      TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro
      (Tumor Necrosis Factor-alpha (TNFalpha), Interleukin (IL)-1beta, IL-6) and anti
      inflammatory cytokines (IL-10) and of vascular inducible NO-Synthase (iNOS) was
      determined using RT-qPCR. Wildtype mice exhibited a significant loss of vascular
      contractility after CASP. This was aggravated in TLR2-D mice, blunted in TLR4-D
      animals and abolished in TLR9-D and CD14-D animals. TNF-alpha expression was
      significantly up-regulated after CASP in wildtype and TLR2-D animals, but not in
      mice deficient for TLR4, -9 or CD14. iNOS was significantly up-regulated in TLR2
      D animals only. TLR2-D animals showed significantly higher levels of TLR4, -9 and
      CD14. Application of H154-ODN, a TLR9 antagonist, attenuated CASP-induced
      cytokine release and vascular dysfunction in wildtype mice. CONCLUSIONS: Within
      our model, CD14 and TLR9 play a decisive role for the development of vascular
      dysfunction and thus can be effectively antagonized using H154-ODN. TLR2-D
      animals are more prone to polymicrobial sepsis, presumably due to up-regulation
      of TLR4, 9 and CD14.

PMID- 22970243
TI  - Hpz1 modulates the G1-S transition in fission yeast.
AB  - Here we characterize a novel protein in S. pombe. It has a high degree of
      homology with the Zn-finger domain of the human Poly(ADP-ribose) polymerase
      (PARP). Surprisingly, the gene for this protein is, in many fungi, fused with and
      in the same reading frame as that encoding Rad3, the homologue of the human ATR
      checkpoint protein. We name the protein Hpz1 (Homologue of PARP-type Zn-finger).
      Hpz1 does not possess PARP activity, but is important for resistance to
      ultraviolet light in the G1 phase and to treatment with hydroxyurea, a drug that
      arrests DNA replication forks in the S phase. However, we find no evidence of a
      checkpoint function of Hpz1. Furthermore, absence of Hpz1 results in an
      advancement of S-phase entry after a G1 arrest as well as earlier recovery from a
      hydroxyurea block. The hpz1 gene is expressed mainly in the G1 phase and Hpz1 is
      localized to the nucleus. We conclude that Hpz1 regulates the initiation of the S
      phase and may cooperate with Rad3 in this function.

PMID- 22970244
TI  - Characterization of isoenzyme-selective inhibitors of human sphingosine kinases.
AB  - Sphingosine kinases (SKs) are promising new therapeutic targets for cancer
      because they regulate the balance between pro-apoptotic ceramides and mitogenic
      sphingosine-1-phosphate. The functions of the two SK isoenzymes, SK1 and SK2, are
      not redundant, with genetic ablation of SK2 having more pronounced anticancer
      effects than removal of SK1. Although several small molecule inhibitors of SKs
      have been described in the literature, detailed characterization of their
      molecular and cellular pharmacology, particularly their activities against human
      SK1 and SK2, have not been completed. Computational modeling of the putative
      active sites of SK1 and SK2 suggests structural differences that might allow
      isozyme-selective inhibitors. Therefore, we characterized several SK-inhibitory
      compounds which revealed differential inhibitory effects on SK1 and SK2 as
      follows: SKI-II and ABC294735 are SK1/2-dual inhibitors; CB5468139 is a SK1
      selective inhibitor; and ABC294640 is a SK2-selective inhibitor. We examined the
      effects of the SK inhibitors on several biochemical and phenotypic processes in
      A498 kidney adenocarcinoma cells. The SK2-selective inhibitor ABC294640
      demonstrated the most pronounced effects on SK1 and SK2 mRNA expression, decrease
      of S1P levels, elevation of ceramide levels, cell cycle arrest, and inhibition of
      proliferation, migration and invasion. ABC294640 also down-regulated the
      expression or activation of several signaling proteins, including STAT3, AKT,
      ERK, p21, p53 and FAK. These effects were equivalent or superior to responses to
      the SK1/2-dual inhibitors. Overall, these results suggest that inhibition of SK2
      results in stronger anticancer effects than does inhibition of SK1 or both SK1
      and SK2.

PMID- 22970245
TI  - MicroRNA-16 is down-regulated in mutated FLT3 expressing murine myeloid FDC-P1
      cells and interacts with Pim-1.
AB  - Activating mutations in the receptor tyrosine kinase FLT3 are one of the most
      frequent somatic mutations in acute myeloid leukemia (AML). Internal tandem
      duplications of the juxtamembrane region of FLT3 (FLT3/ITD) constitutively
      activate survival and proliferation pathways, and are associated with a poor
      prognosis in AML. We suspected that alteration of small non-coding microRNA
      (miRNA) expression in these leukemia cells is involved in the transformation
      process and used miRNA microarrays to determine the miRNA signature from total
      RNA harvested from FLT3/ITD expressing FDC-P1 cells (FD-FLT3/ITD). This revealed
      that a limited set of miRNAs appeared to be affected by expression of FLT3/ITD
      compared to the control group consisting of FDC-P1 parental cells transfected
      with an empty vector (FD-EV). Among differentially expressed miRNAs, we selected
      miR-16, miR-21 and miR-223 to validate the microarray data by quantitative real
      time RT-PCR showing a high degree of correlation. We further analyzed miR-16
      expression with FLT3 inhibitors in FLT3/ITD expressing cells. MiR-16 was found to
      be one of most significantly down-regulated miRNAs in FLT3/ITD expressing cells
      and was up-regulated upon FLT3 inhibition. The data suggests that miR-16 is
      acting as a tumour suppressor gene in FLT3/ITD-mediated leukemic transformation.
      Whilst miR-16 has been reported to target multiple mRNAs, computer models from
      public bioinformatic resources predicted a potential regulatory mechanism between
      miR-16 and Pim-1 mRNA. In support of this interaction, miR-16 was shown to
      suppress Pim-1 reporter gene expression. Further, our data demonstrated that over
      expression of miR-16 mimics suppressed Pim-1 expression in FD-FLT3/ITD cells
      suggesting that increased miR-16 expression contributes to depletion of Pim-1
      after FLT3 inhibition and that miR-16 repression may be associated with up
      regulated Pim-1 in FLT3/ITD expressing cells.

PMID- 22970246
TI  - SU5416, a VEGF receptor inhibitor and ligand of the AHR, represents a new
      alternative for immunomodulation.
AB  - The experimental compound SU5416 went as far as Phase III clinical trials as an
      anticancer agent, putatively because of its activity as a VEGFR-2 inhibitor, but
      showed poor results. Here, we show that SU5416 is also an aryl hydrocarbon
      receptor (AHR) agonist with unique properties. Like TCDD, SU5416 favors induction
      of indoleamine 2,3 dioxygenase (IDO) in immunologically relevant populations such
      as dendritic cells in an AHR-dependent manner, leading to generation of
      regulatory T-cells in vitro. These characteristics lead us to suggest that SU5416
      may be an ideal clinical agent for treatment of autoimmune diseases and
      prevention of transplant rejection, two areas where regulatory ligands of the AHR
      have shown promise. At the same time, AHR agonism might represent a poor
      characteristic for an anticancer drug, as regulatory T-cells can inhibit
      clearance of cancer cells, and activation of the AHR can lead to upregulation of
      xenobiotic metabolizing enzymes that might influence the half-lives of co
      administered chemotherapeutic agents. Not only does SU5416 activate the human AHR
      with a potency approaching 2,3,7,8-tetrachlorodibenzo-p-dioxin, but it also
      activates polymorphic murine receptor isoforms (encoded by the Ahr(d) and Ahr(b1)
      alleles) with similar potency, a finding that has rarely been described and may
      have implications in identifying true endogenous ligands of this receptor.

PMID- 22970247
TI  - Social vocalizations of big brown bats vary with behavioral context.
AB  - Bats are among the most gregarious and vocal mammals, with some species
      demonstrating a diverse repertoire of syllables under a variety of behavioral
      contexts. Despite extensive characterization of big brown bat (Eptesicus fuscus)
      biosonar signals, there have been no detailed studies of adult social
      vocalizations. We recorded and analyzed social vocalizations and associated
      behaviors of captive big brown bats under four behavioral contexts: low
      aggression, medium aggression, high aggression, and appeasement. Even limited to
      these contexts, big brown bats possess a rich repertoire of social vocalizations,
      with 18 distinct syllable types automatically classified using a spectrogram
      cross-correlation procedure. For each behavioral context, we describe
      vocalizations in terms of syllable acoustics, temporal emission patterns, and
      typical syllable sequences. Emotion-related acoustic cues are evident within the
      call structure by context-specific syllable types or variations in the temporal
      emission pattern. We designed a paradigm that could evoke aggressive
      vocalizations while monitoring heart rate as an objective measure of internal
      physiological state. Changes in the magnitude and duration of elevated heart rate
      scaled to the level of evoked aggression, confirming the behavioral state
      classifications assessed by vocalizations and behavioral displays. These results
      reveal a complex acoustic communication system among big brown bats in which
      acoustic cues and call structure signal the emotional state of a caller.

PMID- 22970248
TI  - Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a
      new candidate in the pathogenesis of osteoporosis.
AB  - Th17 cells produce IL-17, and the latter promotes bone loss in collagen-induced
      arthritis in mice. Blocking IL-17 action in mouse model of rheumatoid arthritis
      reduces disease symptoms. These observations suggest that Th17 cells may be
      involved in the pathogenesis of bone loss. However, the role of Th17 cell in
      estrogen (E2) deficiency-induced bone loss is still not very clear. We
      investigated the effect of E2 on Th17 differentiation in vivo and IL-17 mediated
      regulation of osteoclast and osteoblast differentiation. Additionally, effect of
      IL-17 functional block under E2 deficiency-induced bone loss was studied. In
      murine bone marrow cells, E2 suppressed IL-17 mediated osteoclast
      differentiation. IL-17 inhibited formation of mineralized nodules in osteoblasts
      and this effect was suppressed by E2. E2 treatment to mouse calvarial osteoblasts
      inhibited the IL-17-induced production of osteoclastogenic cytokines and NF-kB
      translocation. In ovariectomized mice, there was increase in the number of Th17
      cells, transcription factors promoting Th17 cell differentiation and circulating
      IL-17 levels. These effects were reversed by E2 supplementation. Treatment of
      neutralizing IL-17 monoclonal antibody to Ovx mice mitigated the E2 deficiency
      induced trabecular bone loss and reversed the decreased osteoprotegerin-to
      receptor activator of nuclear factor kappa B ligand (RANKL) transcript levels in
      long bones, increased osteoclast differentiation from the bone marrow precursor
      cells and decreased osteoblast differentiation from the bone marrow stromal
      cells. Our findings indicate that E2 deficiency leads to increased
      differentiation of Th17 cells with attendant up regulation of STAT3, ROR-gammat
      and ROR-alpha and downregulation of Foxp3 which antagonizes Th17 cell
      differentiation. Increased IL-17 production in turn induces bone loss by
      increasing pro-osteoclastogenic cytokines including TNF-alpha, IL-6 and RANKL
      from osteoblasts and functional block of IL-17 prevents bone loss. IL-17 thus
      plays a critical causal role in Ovx-induced bone loss and may be considered a
      potential therapeutic target in pathogenesis of post menopausal osteoporosis.

PMID- 22970249
TI  - Hypoxic induction of the regulator of G-protein signalling 4 gene is mediated by
      the hypoxia-inducible factor pathway.
AB  - The transcriptional response to hypoxia is largely dependent on the Hypoxia
      Inducible Factors (HIF-1 and HIF-2) in mammalian cells. Many target genes have
      been characterised for these heterodimeric transcription factors, yet there is
      evidence that the full range of HIF-regulated genes has not yet been described.
      We constructed a TetON overexpression system in the rat pheochromocytoma PC-12
      cell line to search for novel HIF and hypoxia responsive genes. The Rgs4 gene
      encodes the Regulator of G-Protein Signalling 4 (RGS4) protein, an inhibitor of
      signalling from G-protein coupled receptors, and dysregulation of Rgs4 is linked
      to disease states such as schizophrenia and cardiomyopathy. Rgs4 was found to be
      responsive to HIF-2alpha overexpression, hypoxic treatment, and hypoxia mimetic
      drugs in PC-12 cells. Similar responses were observed in human neuroblastoma cell
      lines SK-N-SH and SK-N-BE(2)C, but not in endothelial cells, where Rgs4
      transcript is readily detected but does not respond to hypoxia. Furthermore, this
      regulation was found to be dependent on transcription, and occurs in a manner
      consistent with direct HIF transactivation of Rgs4 transcription. However, no HIF
      binding site was detectable within 32 kb of the human Rgs4 gene locus, leading to
      the possibility of regulation by long-distance genomic interactions. Further
      research into Rgs4 regulation by hypoxia and HIF may result in better
      understanding of disease states such as schizophrenia, and also shed light on the
      other roles of HIF yet to be discovered.

PMID- 22970250
TI  - Expression profiling of stem cell-related genes in neoadjuvant-treated gastric
      cancer: a NOTCH2, GSK3B and beta-catenin gene signature predicts survival.
AB  - Cancer stem cell (CSC) based gene expression signatures are associated with
      prognosis in various tumour types and CSCs are suggested to be particularly drug
      resistant. The aim of our study was first, to determine the prognostic
      significance of CSC-related gene expression in residual tumour cells of
      neoadjuvant-treated gastric cancer (GC) patients. Second, we wished to examine,
      whether expression alterations between pre- and post-therapeutic tumour samples
      exist, consistent with an enrichment of drug resistant tumour cells. The
      expression of 44 genes was analysed in 63 formalin-fixed, paraffin embedded
      tumour specimens with partial tumour regression (10-50% residual tumour) after
      neoadjuvant chemotherapy by quantitative real time PCR low-density arrays. A
      signature of combined GSK3B(high), beta-catenin (CTNNB1)(high) and NOTCH2(low)
      expression was strongly correlated with better patient survival (p<0.001). A
      prognostic relevance of these genes was also found analysing publically available
      gene expression data. The expression of 9 genes was compared between pre
      therapeutic biopsies and post-therapeutic resected specimens. A significant post
      therapeutic increase in NOTCH2, LGR5 and POU5F1 expression was found in tumours
      with different tumour regression grades. No significant alterations were observed
      for GSK3B and CTNNB1. Immunohistochemical analysis demonstrated a chemotherapy
      associated increase in the intensity of NOTCH2 staining, but not in the
      percentage of NOTCH2. Taken together, the GSK3B, CTNNB1 and NOTCH2 expression
      signature is a novel, promising prognostic parameter for GC. The results of the
      differential expression analysis indicate a prominent role for NOTCH2 and
      chemotherapy resistance in GC, which seems to be related to an effect of the
      drugs on NOTCH2 expression rather than to an enrichment of NOTCH2 expressing
      tumour cells.

PMID- 22970251
TI  - High incidence of multiple viral infections identified in upper respiratory tract
      infected children under three years of age in Shanghai, China.
AB  - BACKGROUND: Upper respiratory tract infection (URTI) is a major reason for
      hospitalization in childhood. More than 80% of URTIs are viral. Etiological
      diagnosis of URTIs is important to make correct clinical decisions on treatment
      methods. However, data for viral spectrum of URTIs are very limited in Shanghai
      children. METHODS: Nasopharyngeal swabs were collected from a group of 164
      children aged below 3 years who were hospitalized due to acute respiratory
      infection from May 2009 to July 2010 in Shanghai. A VRDAL multiplex PCR for 10
      common respiratory viruses was performed on collected specimens compared with the
      Seeplex(r) RV15 ACE Detection kit for 15 respiratory viruses. RESULTS: Viruses
      were detected in 84 (51.2%) patients by VRDAL multiplex PCR, and 8 (4.9%) of
      cases were mixed infections. Using the Seeplex(r) RV15 ACE Detection kit, viruses
      were detected in 129 (78.7%) patients, 49 (29.9%) were co-infected cases.
      Identified viruses included 37 of human rhinovirus (22.6% of cases), 32 of
      influenza A virus (19.5%), 30 of parainfluenzavirus-2 (18.3%), 23 of
      parainfluenzavirus-3 (14.0%), 15 of human enterovirus (9.1%), 14 each of
      parainfluenzavirus-1, respiratory syncytial virus B and adenovirus (8.5%), 8 of
      coronavirus 229E/NL63 (4.9%), 6 of human bocavirus (3.7%), 5 each of influenza B
      virus and respiratory syncytial virus A (3.0%), 3 of parainfluenzavirus-4 (1.8%),
      2 of coronavirus OC43/HKU1 (1.2%), and 1 human metapneumovirus (0.6%).
      CONCLUSIONS: A high frequency of respiratory infections (78.7%) and co-infections
      (29.9%) was detected in children with acute respiratory infection symptoms in
      Shanghai. The Seeplex(r) RV15 ACE detection method was found to be a more
      reliable high throughput tool than VRDAL method to simultaneously detect multiple
      respiratory viruses.

PMID- 22970252
TI  - Communication between corneal epithelial cells and trigeminal neurons is
      facilitated by purinergic (P2) and glutamatergic receptors.
AB  - Previously, we demonstrated that nucleotides released upon mechanical injury to
      corneal epithelium activate purinergic (P2) receptors resulting in mobilization
      of a Ca(2+) wave. However, the tissue is extensively innervated and communication
      between epithelium and neurons is critical and not well understood. Therefore, we
      developed a co-culture of primary trigeminal neurons and human corneal limbal
      epithelial cells. We demonstrated that trigeminal neurons expressed a repertoire
      of P2Yand P2X receptor transcripts and responded to P2 agonists in a
      concentration-dependent manner. Mechanical injuries to epithelia in the co
      cultures elicited a Ca(2+) wave that mobilized to neurons and was attenuated by
      Apyrase, an ectonucleotidase. To elucidate the role of factors released from each
      cell type, epithelial and neuronal cells were cultured, injured, and the wound
      media from one cell type was collected and added to the other cell type.
      Epithelial wound media generated a rapid Ca(2+) mobilization in neuronal cells
      that was abrogated in the presence of Apyrase, while neuronal wound media
      elicited a complex response in epithelial cells. The rapid Ca(2+) mobilization
      was detected, which was abrogated with Apyrase, but it was followed by Ca(2+)
      waves that occurred in cell clusters. When neuronal wound media was preincubated
      with a cocktail of N-methyl-D-aspartate (NMDA) receptor inhibitors, the secondary
      response in epithelia was diminished. Glutamate was detected in the neuronal
      wound media and epithelial expression of NMDA receptor subunit transcripts was
      demonstrated. Our results indicate that corneal epithelia and neurons communicate
      via purinergic and NMDA receptors that mediate the wound response in a highly
      orchestrated manner.

PMID- 22970253
TI  - Thiol/Disulfide system plays a crucial role in redox protection in the
      acidophilic iron-oxidizing bacterium Leptospirillum ferriphilum.
AB  - Thiol/disulfide systems are involved in the maintenance of the redox status of
      proteins and other molecules that contain thiol/disulfide groups. Leptospirillum
      ferriphilum DSM14647, an acidophilic bacterium that uses Fe(2+) as electron
      donor, and withstands very high concentrations of iron and other redox active
      metals, is a good model to study how acidophiles preserve the thiol/disulfide
      balance. We studied the composition of thiol/disulfide systems and their role in
      the oxidative stress response in this extremophile bacterium. Bioinformatic
      analysis using genomic data and enzymatic assays using protein extracts from
      cells grown under oxidative stress revealed that the major thiol/disulfide system
      from L. ferriphilum are a cytoplasmic thioredoxin system (composed by
      thioredoxins Trx and thioredoxin reductase TR), periplasmic thiol oxidation
      system (DsbA/DsbB) and a c-type cytochrome maturation system (DsbD/DsbE). Upon
      exposure of L. ferriphilum to reactive oxygen species (ROS)-generating compounds,
      transcriptional activation of the genes encoding Trxs and the TR enzyme, which
      results in an increase of the corresponding activity, was observed. Altogether
      these data suggest that the thioredoxin-based thiol/disulfide system plays an
      important role in redox protection of L. ferriphilum favoring the survival of
      this microorganism under extreme environmental oxidative conditions.

PMID- 22970254
TI  - Transforming growth factor-beta promotes rhinovirus replication in bronchial
      epithelial cells by suppressing the innate immune response.
AB  - Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be
      due to a deficient innate immune response in the bronchial epithelium. We
      hypothesized that the pleiotropic cytokine, TGF-beta, influences interferon (IFN)
      production by primary bronchial epithelial cells (PBECs) following RV infection.
      Exogenous TGF-beta(2) increased RV replication and decreased IFN protein
      secretion in response to RV or double-stranded RNA (dsRNA). Conversely,
      neutralizing TGF-beta antibodies decreased RV replication and increased IFN
      expression in response to RV or dsRNA. Endogenous TGF-beta(2) levels were higher
      in conditioned media of PBECs from asthmatic donors and the suppressive effect of
      anti-TGF-beta on RV replication was significantly greater in these cells. Basal
      SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF
      beta and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our
      results suggest that endogenous TGF-beta contributes to a suppressed IFN response
      to RV infection possibly via SOCS-1 and SOCS-3.

PMID- 22970255
TI  - Cell division site placement and asymmetric growth in mycobacteria.
AB  - Mycobacteria are members of the actinomycetes that grow by tip extension and lack
      apparent homologues of the known cell division regulators found in other rod
      shaped bacteria. Previous work using static microscopy on dividing mycobacteria
      led to the hypothesis that these cells can grow and divide asymmetrically, and at
      a wide range of sizes, in contrast to the cell growth and division patterns
      observed in the model rod-shaped organisms. In this study, we test this
      hypothesis using live-cell time-lapse imaging of dividing Mycobacterium smegmatis
      labelled with fluorescent PBP1a, to probe peptidoglycan synthesis and label the
      cell septum. We demonstrate that the new septum is placed accurately at mid-cell,
      and that the asymmetric division observed is a result of differential growth from
      the cell tips, with a more than 2-fold difference in growth rate between fast and
      slow growing poles. We also show that the division site is not selected at a
      characteristic cell length, suggesting this is not an important cue during the
      mycobacterial cell cycle.

PMID- 22970256
TI  - Measurements of DNA methylation at seven loci in various tissues of CD1 mice.
AB  - In humans, considerable variation in methylation at single loci and repetitive
      elements in various cells and tissues is observed. Recently, several inter- and
      intra-tissue correlations for DNA methylation have been reported. To investigate
      the extent and reproducibility of such correlations, we investigated inter- and
      intra-tissue methylation correlations among seven different loci in 9 different
      tissues in a population of 100 healthy seven-week-old CD1 outbred mice. We used a
      highly quantitative approach to measure methylation levels to high accuracy at
      two single loci in the alpha-actin and myosine light chain promoters, at three
      differentially methylated regions of the Peg3, Snrpn and Lit1 genes associated
      with imprinted loci, and at two repetitive elements in the Line-1 and IAP-LTR
      genes in the various tissues. In this population of mice, methylation at several
      loci was sex-associated and intra-tissue correlations among the studied loci were
      observed for brain and spleen. Inter-tissue correlations were rarely observed. To
      investigate method-dependent experimental variability, we re-analyzed the same
      spleen and tongue samples using SIRPH and pyrosequencing methods and reconfirmed
      intra-tissue correlations for spleen and sex-associated correlations for DNA
      methylation for tongue. When we repeated DNA methylation measurements for a
      second mouse population raised under similar conditions three months later, we
      did not detect sex-associated or intra-tissues correlations. Additional studies
      that examine large numbers of loci may be required to further understand the
      factors that influence stability of DNA methylation.

PMID- 22970257
TI  - Congruent strain specific intestinal persistence of Lactobacillus plantarum in an
      intestine-mimicking in vitro system and in human volunteers.
AB  - BACKGROUND: An important trait of probiotics is their capability to reach their
      intestinal target sites alive to optimally exert their beneficial effects.
      Assessment of this trait in intestine-mimicking in vitro model systems has
      revealed differential survival of individual strains of a species. However, data
      on the in situ persistence characteristics of individual or mixtures of strains
      of the same species in the gastrointestinal tract of healthy human volunteers
      have not been reported to date. METHODOLOGY/PRINCIPAL FINDINGS: The GI-tract
      survival of individual L. plantarum strains was determined using an intestine
      mimicking model system, revealing substantial inter-strain differences. The
      obtained data were correlated to genomic diversity of the strains using
      comparative genome hybridization (CGH) datasets, but this approach failed to
      discover specific genetic loci that explain the observed differences between the
      strains. Moreover, we developed a next-generation sequencing-based method that
      targets a variable intergenic region, and employed this method to assess the in
      vivo GI-tract persistence of different L. plantarum strains when administered in
      mixtures to healthy human volunteers. Remarkable consistency of the strain
      specific persistence curves were observed between individual volunteers, which
      also correlated significantly with the GI-tract survival predicted on basis of
      the in vitro assay. CONCLUSION: The survival of individual L. plantarum strains
      in the GI-tract could not be correlated to the absence or presence of specific
      genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo
      persistence analysis in the human GI-tract confirmed the strain-specific
      persistence, which appeared to be remarkably similar in different healthy
      volunteers. Moreover, the relative strain-specific persistence in vivo appeared
      to be accurately and significantly predicted by their relative survival in the
      intestine-mimicking in vitro assay, supporting the use of this assay for
      screening of strain-specific GI persistence.

PMID- 22970258
TI  - Modelling the arrival of invasive organisms via the international marine shipping
      network: a Khapra beetle study.
AB  - Species can sometimes spread significant distances beyond their natural dispersal
      ability by anthropogenic means. International shipping routes and the transport
      of shipping containers, in particular are a commonly recognised pathway for the
      introduction of invasive species. Species can gain access to a shipping container
      and remain inside, hidden and undetected for long periods. Currently, government
      biosecurity agencies charged with intercepting and removing these invasive
      species when they arrive to a county's border only assess the most immediate
      point of loading in evaluating a shipping container's risk profile. However, an
      invasive species could have infested a container previous to this point and
      travelled undetected before arriving at the border. To assess arrival risk for an
      invasive species requires analysing the international shipping network in order
      to identify the most likely source countries and the domestic ports of entry
      where the species is likely to arrive. We analysed an international shipping
      network and generated pathway simulations using a first-order Markov chain model
      to identify possible source ports and countries for the arrival of Khapra beetle
      (Trogoderma granarium) to Australia. We found Kaohsiung (Taiwan) and Busan
      (Republic of Korea) to be the most likely sources for Khapra beetle arrival,
      while the port of Melbourne was the most likely point of entry to Australia.
      Sensitivity analysis revealed significant stability in the rankings of foreign
      and Australian ports. This methodology provides a reliable modelling tool to
      identify and rank possible sources for an invasive species that could arrive at
      some time in the future. Such model outputs can be used by biosecurity agencies
      concerned with inspecting incoming shipping containers and wishing to optimise
      their inspection protocols.

PMID- 22970259
TI  - PI3K p110alpha isoform-dependent Rho GTPase Rac1 activation mediates H2S-promoted
      endothelial cell migration via actin cytoskeleton reorganization.
AB  - Hydrogen sulfide (H(2)S) is now considered as the third gaseotransmitter,
      however, the signaling pathways that modulate the biomedical effect of H(2)S on
      endothelial cells are poorly defined. In the present study, we found in human
      endothelial cells that H(2)S increased cell migration rates and induced a marked
      reorganization of the actin cytoskeleton, which was prevented by depletion of
      Rac1. Pharmacologic inhibiting vascular endothelial growth factor receptor
      (VEGFR) and phosphoinositide 3-kinase (PI3K) both blunted the activation of Rac1
      and the promotion of cell migration induced by H(2)S. Moreover, H(2)S-induced
      Rac1 activation was selectively dependent on the presence of the PI3K p110alpha
      isoform. Activated Rac1 by H(2)S thus in turn resulted in the phosphorylation of
      the F-actin polymerization modulator, cofilin. Additionally, inhibiting of
      extracellular signal-regulated kinase (ERK) decreased the augmented cell
      migration rate by H(2)S, but had no effect on Rac1 activation. These results
      indicate that Rac1 conveys the H(2)S signal to microfilaments inducing
      rearrangements of actin cytoskeleton that regulates cell migration. VEGFR-PI3K
      was found to be upstream pathway of Rac1, while cofilin acted as a downstream
      effector of Rac1. ERK was also shown to be involved in the action of H(2)S on
      endothelial cell migration, but independently of Rac1.

PMID- 22970261
TI  - Towards a postural indicator of back pain in horses (Equus caballus).
AB  - Postures have long been used and proved useful to describe animals' behaviours
      and emotional states, but remains difficult to assess objectively in field
      conditions. A recent study performed on horses using geometric morphometrics
      revealed important postural differences between 2 horse populations differing in
      management conditions (leisure horses living in social groups used for occasional
      "relaxed" riding/riding school horses living in individual boxes used in daily
      riding lessons with more constraining techniques). It was suggested that these
      postural differences may reflect chronic effects of riding techniques on the
      horses' kinematics and muscular development. In the present study, we tried to
      evaluate the interest of postural measures to assess welfare in horses. This
      study was separated into 2 parts. First, 18 horses coming from these 2 types of
      populations (leisure/riding school horses) were submitted to 2 back evaluations
      by 1) manual examination (experienced practitioner) and 2) sEMG measures along
      the spine. We then measured neck roundness on 16 of these 18 horses. The results
      highlighted high correlations between manual and sEMG examinations over the
      spine. sEMG measures at the different locations were strongly correlated all over
      the spine. Moreover, neck postures and muscular activities were strongly
      correlated, horses with concave necks having higher sEMG measures both at precise
      locations (i.e. cervical sites) but also when comparing neck postures to the
      whole spine muscular activity highlighting the functioning of horses' back as a
      whole. Lastly, strong differences appeared between the populations, leisure
      horses being evaluated as having sounder spines, exhibiting lower sEMG measures
      and rounder neck than the riding school horses. sEMG measures and neck
      "roundness" seemed therefore to be reliable indicators of back disorders, easy to
      evaluate in field conditions. This highlights the accuracy of using postural
      elements to evaluate the animals' general state and has important implications
      for animals' welfare evaluations.

PMID- 22970260
TI  - Sulfur metabolizing microbes dominate microbial communities in Andesite-hosted
      shallow-sea hydrothermal systems.
AB  - To determine microbial community composition, community spatial structure and
      possible key microbial processes in the shallow-sea hydrothermal vent systems off
      NE Taiwan's coast, we examined the bacterial and archaeal communities of four
      samples collected from the water column extending over a redoxocline gradient of
      a yellow and four from a white hydrothermal vent. Ribosomal tag pyrosequencing
      based on DNA and RNA showed statistically significant differences between the
      bacterial and archaeal communities of the different hydrothermal plumes. The
      bacterial and archaeal communities from the white hydrothermal plume were
      dominated by sulfur-reducing Nautilia and Thermococcus, whereas the yellow
      hydrothermal plume and the surface water were dominated by sulfide-oxidizing
      Thiomicrospira and Euryarchaeota Marine Group II, respectively. Canonical
      correspondence analyses indicate that methane (CH(4)) concentration was the only
      statistically significant variable that explains all community cluster patterns.
      However, the results of pyrosequencing showed an essential absence of methanogens
      and methanotrophs at the two vent fields, suggesting that CH(4) was less tied to
      microbial processes in this shallow-sea hydrothermal system. We speculated that
      mixing between hydrothermal fluids and the sea or meteoric water leads to
      distinctly different CH(4) concentrations and redox niches between the yellow and
      white vents, consequently influencing the distribution patterns of the free
      living Bacteria and Archaea. We concluded that sulfur-reducing and sulfide
      oxidizing chemolithoautotrophs accounted for most of the primary biomass
      synthesis and that microbial sulfur metabolism fueled microbial energy flow and
      element cycling in the shallow hydrothermal systems off the coast of NE Taiwan.

PMID- 22970262
TI  - An exported heat shock protein 40 associates with pathogenesis-related knobs in
      Plasmodium falciparum infected erythrocytes.
AB  - Cell surface structures termed knobs are one of the most important pathogenesis
      related protein complexes deployed by the malaria parasite Plasmodium falciparum
      at the surface of the infected erythrocyte. Despite their relevance to the
      disease, their structure, mechanisms of traffic and their process of assembly
      remain poorly understood. In this study, we have explored the possible role of a
      parasite-encoded Hsp40 class of chaperone, namely PFB0090c/PF3D7_0201800
      (KAHsp40) in protein trafficking in the infected erythrocyte. We found the gene
      coding for PF3D7_0201800 to be located in a chromosomal cluster together with
      knob components KAHRP and PfEMP3. Like the knob components, KAHsp40 too showed
      the presence of PEXEL motif required for transport to the erythrocyte
      compartment. Indeed, sub-cellular fractionation and immunofluorescence analysis
      (IFA) showed KAHsp40 to be exported in the erythrocyte cytoplasm in a stage
      dependent manner localizing as punctuate spots in the erythrocyte periphery,
      distinctly from Maurer's cleft, in structures which could be the reminiscent of
      knobs. Double IFA analysis revealed co-localization of PF3D7_0201800 with the
      markers of knobs (KAHRP, PfEMP1 and PfEMP3) and components of the PEXEL
      translocon (Hsp101, PTEX150). KAHsp40 was also found to be in a complex with
      KAHRP, PfEMP3 and Hsp101 as confirmed by co-immunoprecipitation assay. Our
      results suggest potential involvement of a parasite encoded Hsp40 in chaperoning
      knob assembly in the erythrocyte compartment.

PMID- 22970264
TI  - Phosphorylation-dependent SUMOylation of the transcription factor NF-E2.
AB  - Nuclear factor erythroid-derived 2 (NF-E2), a heterodimer composed of p45 and
      p18, is a transcriptional activator in hematopoietic progenitors. The
      transcriptional activity of NF-E2 is not only upregulated by SUMOylation but also
      stimulated by the cAMP-dependent protein kinase A (PKA). However, the
      relationship between SUMOylation and phosphorylation in the activation of NF-E2
      is unclear. In the present studies, we have demonstrated that PKA enhances NF-E2
      SUMOylation in an in vitro system using purified proteins, suggesting a possible
      mechanism for PKA-dependent activation of the NF-E2 transcription factor through
      SUMOylation.

PMID- 22970263
TI  - Comparative transcriptome analyses of deltamethrin-resistant and -susceptible
      Anopheles gambiae mosquitoes from Kenya by RNA-Seq.
AB  - Malaria causes more than 300 million clinical cases and 665,000 deaths each year,
      and the majority of the mortality and morbidity occurs in sub-Saharan Africa. Due
      to the lack of effective vaccines and wide-spread resistance to antimalarial
      drugs, mosquito control is the primary method of malaria prevention and control.
      Currently, malaria vector control relies on the use of insecticides, primarily
      pyrethroids. The extensive use of insecticides has imposed strong selection
      pressures for resistance in the mosquito populations. Consequently, resistance to
      pyrethroids in Anopheles gambiae, the main malaria vector in sub-Saharan Africa,
      has become a major obstacle for malaria control. A key element of resistance
      management is the identification of resistance mechanisms and subsequent
      development of reliable resistance monitoring tools. Field-derived An. gambiae
      from Western Kenya were phenotyped as deltamethrin-resistant or -susceptible by
      the standard WHO tube test, and their expression profile compared by RNA-seq.
      Based on the current annotation of the An. gambiae genome, a total of 1,093
      transcripts were detected as significantly differentially accumulated between
      deltamethrin-resistant and -susceptible mosquitoes. These transcripts are
      distributed over the entire genome, with a large number mapping in QTLs
      previously linked to pyrethorid resistance, and correspond to heat-shock
      proteins, metabolic and transport functions, signal transduction activities,
      cytoskeleton and others. The detected differences in transcript accumulation
      levels between resistant and susceptible mosquitoes reflect transcripts directly
      or indirectly correlated with pyrethroid resistance. RNA-seq data also were used
      to perform a de-novo Cufflinks assembly of the An. gambiae genome.

PMID- 22970266
TI  - Functional status and all-cause mortality in serious mental illness.
AB  - BACKGROUND: Serious mental illness can affect many aspects of an individual's
      ability to function in daily life. The aim of this investigation was to determine
      if the environmental and functional status of people with serious mental illness
      contribute to the high mortality risk observed in this patient group. METHODS: We
      identified cases of schizophrenia, schizoaffective and bipolar disorder aged >=
      15 years in a large secondary mental healthcare case register linked to national
      mortality tracing. We modelled the effect of activities of daily living (ADLs),
      living conditions, occupational and recreational activities and relationship
      factors (Health of the Nation Outcome Scale [HoNOS] subscales) on all-cause
      mortality over a 4-year observation period (2007-10) using Cox regression.
      RESULTS: We identified 6,880 SMI cases (242 deaths) in the observation period.
      ADL impairment was associated with an increased risk of all-cause mortality
      (adjusted HR 1.9; 95% CI 1.3-2.8; p = 0.001, p for trend across ADL categories =
      0.001) after controlling for a broad range of covariates (including demographic
      factors, physical health, mental health symptoms and behaviours, socio-economic
      status and mental health service contact). No associations were found for the
      other three exposures. Stratification by age indicated that ADLs were most
      strongly associated with mortality in the youngest (15 to <35 years) and oldest
      (>= 55 years) groups. CONCLUSIONS: Functional impairment in people with serious
      mental illness diagnoses is a marker of increased mortality risk, possibly in
      younger age groups as a marker of negative symptomatology.

PMID- 22970265
TI  - Distinct effects of rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine
      on cellular bioenergetics and cell death.
AB  - Parkinson's disease is characterized by dopaminergic neurodegeneration and is
      associated with mitochondrial dysfunction. The bioenergetic susceptibility of
      dopaminergic neurons to toxins which induce Parkinson's like syndromes in animal
      models is then of particular interest. For example, rotenone, 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4
      phenylpyridinium (MPP(+)), and 6-hydroxydopamine (6-OHDA), have been shown to
      induce dopaminergic cell death in vivo and in vitro. Exposure of animals to these
      compounds induce a range of responses characteristics of Parkinson's disease,
      including dopaminergic cell death, and Reactive Oxygen Species (ROS) production.
      Here we test the hypothesis that cellular bioenergetic dysfunction caused by
      these compounds correlates with induction of cell death in differentiated
      dopaminergic neuroblastoma SH-SY5Y cells. At increasing doses, rotenone induced
      significant cell death accompanied with caspase 3 activation. At these
      concentrations, rotenone had an immediate inhibition of mitochondrial basal
      oxygen consumption rate (OCR) concomitant with a decrease of ATP-linked OCR and
      reserve capacity, as well as a stimulation of glycolysis. MPP(+) exhibited a
      different behavior with less pronounced cell death at doses that nearly
      eliminated basal and ATP-linked OCR. Interestingly, MPP(+), unlike rotenone,
      stimulated bioenergetic reserve capacity. The effects of 6-OHDA on bioenergetic
      function was markedly less than the effects of rotenone or MPP(+) at cytotoxic
      doses, suggesting a mechanism largely independent of bioenergetic dysfunction.
      These studies suggest that these dopaminergic neurotoxins induce cell death
      through distinct mechanisms and differential effects on cellular bioenergetics.

PMID- 22970267
TI  - Differences in recruitment and life-history strategy alter zooplankton spring
      dynamics under climate-change conditions.
AB  - In recent decades temperature elevation has been the focus of many studies on
      climate change, including effects on planktonic communities, but few studies have
      examined the effects of increased water color ("brownification"). Since these
      changes are likely to occur simultaneously, it is important to investigate their
      potential interactive effects. Accordingly, we performed a mesocosm experiment
      where we combined a 3  degrees C increase in temperature with a doubling in water
      color to study how these factors affect zooplankton. In particular, we looked at
      recruitment of cladocerans and copepods from the sediment in spring, as well as
      their establishment in the water column. Our results show that an elevated
      temperature will have considerable effects on recruitment as well as on pelagic
      abundances of both cladocerans and copepods, whereas increases in water color
      will have less effects on the recruitment and pelagic establishment. But more
      importantly, the proportion of cladocerans in the water column, relative to
      copepods, increased at higher temperature, suggesting that cladocerans benefit
      more from elevated temperatures than copepods do. Overall, these results likely
      stem from the combined effect of changes in recruitment and differences in life
      history between copepods and cladocerans. Taking a wider outlook, this suggests
      that future climate warming will change the dominance pattern of zooplankton
      communities in spring, and, in accordance with the experimental data, we here
      show that cladocerans are more abundant than copepods in natural lake ecosystems
      during warmer rather than cooler years.

PMID- 22970268
TI  - Revealing the molecular mechanism of gastric cancer marker annexin A4 in cancer
      cell proliferation using exon arrays.
AB  - Gastric cancer is a malignant disease that arises from the gastric epithelium. A
      potential biomarker for gastric cancer is the protein annexin A4 (ANXA4), an
      intracellular Ca(2+) sensor. ANXA4 is primarily found in epithelial cells, and is
      known to be involved in various biological processes, including apoptosis, cell
      cycling and anticoagulation. In respect to cancer, ANXA4-overexpression has been
      observed in cancers of various origins, including gastric tumors associated with
      Helicobacter pylori infection. H. pylori induces ANXA4 expression and
      intracellular [Ca(2+)](i) elevation, and is an important risk factor for
      carcinogenesis that results in gastric cancer. Despite this correlation, the role
      of ANXA4 in the progression of gastric tumors remains unclear. In this study, we
      have investigated whether ANXA4 can mediate the rate of cell growth and whether
      ANXA4 downstream signals are involved in tumorigenesis. After observing the rate
      of cell growth in real-time, we determined that ANXA4 promotes cell
      proliferation. The transcription gene profile of ANXA4-overexpressing cells was
      measured and analyzed by human exon arrays. From this transcriptional gene data,
      we show that overexpression of ANXA4 regulates genes that are known to be related
      to cancer, for example the activation of hyaluronan mediated motility receptor
      (RHAMM), AKT, and cyclin-dependent kinase 1 (CDK1) as well as the suppression of
      p21. The regulation of these genes further induces cancer cell proliferation. We
      also found Ca(2+) could regulate the transmission of downstream signals by ANXA4.
      We suggest that ANXA4 triggers a signaling cascade, leading to increased
      epithelial cell proliferation, ultimately promoting carcinogenesis. These results
      might therefore provide a new insight for gastric cancer therapy, specifically
      through the modification of ANXA4 activity.

PMID- 22970269
TI  - Opinions from the front lines of cat colony management conflict.
AB  - Outdoor cats represent a global threat to terrestrial vertebrate conservation,
      but management has been rife with conflict due to differences in views of the
      problem and appropriate responses to it. To evaluate these differences we
      conducted a survey of opinions about outdoor cats and their management with two
      contrasting stakeholder groups, cat colony caretakers (CCCs) and bird
      conservation professionals (BCPs) across the United States. Group opinions were
      polarized, for both normative statements (CCCs supported treating feral cats as
      protected wildlife and using trap neuter and release [TNR] and BCPs supported
      treating feral cats as pests and using euthanasia) and empirical statements.
      Opinions also were related to gender, age, and education, with females and older
      respondents being less likely than their counterparts to support treating feral
      cats as pests, and females being less likely than males to support euthanasia.
      Most CCCs held false beliefs about the impacts of feral cats on wildlife and the
      impacts of TNR (e.g., 9% believed feral cats harmed bird populations, 70%
      believed TNR eliminates cat colonies, and 18% disagreed with the statement that
      feral cats filled the role of native predators). Only 6% of CCCs believed feral
      cats carried diseases. To the extent the beliefs held by CCCs are rooted in lack
      of knowledge and mistrust, rather than denial of directly observable phenomenon,
      the conservation community can manage these conflicts more productively by
      bringing CCCs into the process of defining data collection methods, defining
      study/management locations, and identifying common goals related to caring for
      animals.

PMID- 22970270
TI  - Reproductive status is associated with the severity of fibrosis in women with
      hepatitis C.
AB  - INTRODUCTION: Chronic hepatitis C is the main cause of death in patients with end
      stage liver disease. Prognosis depends on the increase of fibrosis, whose
      progression is twice as rapid in men as in women. Aim of the study was to
      evaluate the effects of reproductive stage on fibrosis severity in women and to
      compare these findings with age-matched men. MATERIALS AND METHODS: A
      retrospective study of 710 consecutive patients with biopsy-proven chronic
      hepatitis C was conducted, using data from a clinical database of two tertiary
      Italian care centers. Four age-matched groups of men served as controls. Data
      about demographics, biochemistry, liver biopsy and ultrasonography were analyzed.
      Contributing factors were assessed by multivariate logistic regression analysis.
      RESULTS: Liver fibrosis was more advanced in the early menopausal than in the
      fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal
      women had higher liver fibrosis compared with the other groups (fully
      reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052).
      Multivariate analyses showed that male sex was independently associated with more
      severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and
      early menopausal (P = 0.004) but not late menopausal pairs. In women,
      estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P
      = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive
      age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal
      women, estradiol/testosterone ratio instead increased (reproductive age group vs.
      early: P = 0.002 and vs. late M: P = 0.001). CONCLUSIONS: The severity of
      fibrosis in women worsens in parallel with increasing estrogen deprivation and
      estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis
      progression is discontinuous in women and more linear and severe in men, in whom
      aging-associated estradiol/testosterone ratio increase occurs too late to
      noticeably influence the inflammatory process leading to fibrosis.

PMID- 22970271
TI  - A diagnostic accuracy study of Xpert(r)MTB/RIF in HIV-positive patients with high
      clinical suspicion of pulmonary tuberculosis in Lima, Peru.
AB  - BACKGROUND: Diagnosis of pulmonary tuberculosis (TB) among human immunodeficiency
      virus (HIV) patients remains complex and demands easy to perform and accurate
      tests. Xpert(r)MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid
      and convenient; the test requires minimal human resources and reports results
      within two hours. The majority of performance studies of MTB/RIF have been
      performed in high HIV burden settings, thus TB diagnostic studies among HIV
      patients in low HIV prevalence settings such as Peru are still needed.
      METHODOLOGY/PRINCIPAL FINDINGS: From April 2010 to May 2011, HIV-positive
      patients with high clinical suspicion of TB were enrolled from two tertiary
      hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite
      reference standard Lowenstein-Jensen (LJ) and liquid culture. Detection of
      rifampicin resistance was compared to the LJ proportion method. We included 131
      patients, the median CD4 cell count was 154.5 cells/mm(3) and 45 (34.4%) had TB.
      For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI
      88.4-99.6) (44/45); specificity was 97.7% (95% CI 91.9-99.4) (84/86); the
      positive predictive value was 95.7% (95% CI 85.5-98.8) (44/46); and the negative
      predictive value, 98.8% (95% CI 93.6-99.8) (84/85). MTB/RIF detected 13/14 smear
      negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9%
      (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF
      was 100% (95% CI 61.0-100.0) (6/6); specificity was 91.0% (95% CI 76.4-96.9)
      (30/33); the positive predictive value was 66.7% (95% CI 35.4-87.9) (6/9); and
      the negative predictive value was 100% (95% CI 88.7 -100.0) (30/30).
      CONCLUSIONS/SIGNIFICANCE: In HIV patients in our population with a high clinical
      suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear
      microscopy.

PMID- 22970272
TI  - Role of Ca2+ in the control of H2O2-modulated phosphorylation pathways leading to
      eNOS activation in cardiac myocytes.
AB  - Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) play key roles in
      physiological and pathological responses in cardiac myocytes. The mechanisms
      whereby H(2)O(2)-modulated phosphorylation pathways regulate the endothelial
      isoform of nitric oxide synthase (eNOS) in these cells are incompletely
      understood. We show here that H(2)O(2) treatment of adult mouse cardiac myocytes
      leads to increases in intracellular Ca(2+) ([Ca(2+)](i)), and document that
      activity of the L-type Ca(2+) channel is necessary for the H(2)O(2)-promoted
      increase in sarcomere shortening and of [Ca(2+)](i). Using the chemical NO sensor
      Cu(2)(FL2E), we discovered that the H(2)O(2)-promoted increase in cardiac myocyte
      NO synthesis requires activation of the L-type Ca(2+) channel, as well as
      phosphorylation of the AMP-activated protein kinase (AMPK), and mitogen-activated
      protein kinase kinase 1/2 (MEK1/2). Moreover, H(2)O(2)-stimulated
      phosphorylations of eNOS, AMPK, MEK1/2, and ERK1/2 all depend on both an increase
      in [Ca(2+)](i) as well as the activation of protein kinase C (PKC). We also found
      that H(2)O(2)-promoted cardiac myocyte eNOS translocation from peripheral
      membranes to internal sites is abrogated by the L-type Ca(2+) channel blocker
      nifedipine. We have previously shown that kinase Akt is also involved in H(2)O(2)
      promoted eNOS phosphorylation. Here we present evidence documenting that H(2)O(2)
      promoted Akt phosphorylation is dependent on activation of the L-type Ca(2+)
      channel, but is independent of PKC. These studies establish key roles for Ca(2+)-
      and PKC-dependent signaling pathways in the modulation of cardiac myocyte eNOS
      activation by H(2)O(2).

PMID- 22970273
TI  - The differential effect of NAT2 variant alleles permits refinement in phenotype
      inference and identifies a very slow acetylation genotype.
AB  - Indirect evidences suggest that acetylation phenotype categories are
      heterogeneous and that subcategories, related to specific NAT2 variant alleles
      might exist. We analyzed the in vivo acetylation phenotype and genotype in 504
      north-American subjects of Caucasian origin. The analyses of the SNPs rs1801280
      and rs1799930 allowed the discrimination of five categories with different
      acetylation status within the study population. These categories are related to
      the distinct effect of NAT2 alleles on the acetylation status in vivo and to the
      occurrence of a gene-dose effect. These five phenotype categories, from higher to
      lower acetylation capacity, correspond to the genotypes NAT2*4/*4, NAT2*4/*5 or
      *4/*6, NAT2*5/*5, NAT2*5/*6 and NAT2*6/*6 (p <= 0.001 for all comparisons). The
      NAT2*6/*6 genotype correspond to a phenotype category of very-slow acetylators.
      The refinement in phenotype prediction may help to identify risks associated to
      phenotype subcategories, and warrants the re-analysis of previous studies that
      may have overlooked phenotype subcategory-specific risks.

PMID- 22970274
TI  - Development of multicellular tumor spheroid (MCTS) culture from breast cancer
      cell and a high throughput screening method using the MTT assay.
AB  - In comparison to monolayer cells, MCTS has been claimed as more suitable
      candidate for studying drug penetration due to the high resemblance to solid
      tumors. However, the cultivation of MCTS is cumbersome, time consuming, and most
      technique fail to generate spheroids with uniform sizes. Therefore, the
      application of spheroid cultures in high throughput screening has been rather
      limiting. Besides, the lack of a well established screening protocol method that
      is applicable to spheroid could also be attributed to this limitation. Here we
      report a simple way of cultivating homogenous MCTS cultures with compact and
      rigid structure from the MCF-7 cells. Besides, we had also made some
      modifications to the standard MTT assay to realize high throughput screening of
      these spheroids. Using the modified protocol, tamoxifen showed cytotoxicity
      effect towards MCTS cultures from MCF-7 with high consistency. The results
      correlated well with the cultures' response assessed by LDH release assay but the
      latter assay was not ideal for detecting a wide range of cytotoxicity due to high
      basal background reading. The MTT assay emerged as a better indicator to
      apoptosis event in comparison to the LDH release assay. Therefore, the method for
      spheroid generation and the modified MTT assay we reported here could be
      potentially applied to high throughput screening for response of spheroid
      cultures generated from MCF-7 as well as other cancer cell lines towards
      cytotoxic stimuli.

PMID- 22970275
TI  - Comparing effects of lake- and watershed-scale influences on communities of
      aquatic invertebrates in shallow lakes.
AB  - Constraints on lake communities are complex and are usually studied by using
      limited combinations of variables derived from measurements within or adjacent to
      study waters. While informative, results often provide limited insight about
      magnitude of simultaneous influences operating at multiple scales, such as lake-
      vs. watershed-scale. To formulate comparisons of such contrasting influences, we
      explored factors controlling the abundance of predominant aquatic invertebrates
      in 75 shallow lakes in western Minnesota, USA. Using robust regression
      techniques, we modeled relative abundance of Amphipoda, small and large
      cladocera, Corixidae, aquatic Diptera, and an aggregate taxon that combined
      Ephemeroptera-Trichoptera-Odonata (ETO) in response to lake- and watershed-scale
      characteristics. Predictor variables included fish and submerged plant abundance,
      linear distance to the nearest wetland or lake, watershed size, and proportion of
      the watershed in agricultural production. Among-lake variability in invertebrate
      abundance was more often explained by lake-scale predictors than by variables
      based on watershed characteristics. For example, we identified significant
      associations between fish presence and community type and abundance of small and
      large cladocera, Amphipoda, Diptera, and ETO. Abundance of Amphipoda, Diptera,
      and Corixidae were also positively correlated with submerged plant abundance. We
      observed no associations between lake-watershed variables and abundance of our
      invertebrate taxa. Broadly, our results seem to indicate preeminence of lake
      level influences on aquatic invertebrates in shallow lakes, but historical land
      use legacies may mask important relationships.

PMID- 22970276
TI  - The sortase A substrates FnbpA, FnbpB, ClfA and ClfB antagonize colony spreading
      of Staphylococcus aureus.
AB  - Staphylococcus aureus is an important human pathogen that is renowned both for
      its rapid transmission within hospitals and the community, and for the formation
      of antibiotic resistant biofilms on medical implants. Recently, it was shown that
      S. aureus is able to spread over wet surfaces. This motility phenomenon is
      promoted by the surfactant properties of secreted phenol-soluble modulins (PSMs),
      which are also known to inhibit biofilm formation. The aim of the present studies
      was to determine whether any cell surface-associated S. aureus proteins have an
      impact on colony spreading. To this end, we analyzed the spreading capabilities
      of strains lacking non-essential components of the protein export and sorting
      machinery. Interestingly, our analyses reveal that the absence of sortase A
      (SrtA) causes a hyper-spreading phenotype. SrtA is responsible for covalent
      anchoring of various proteins to the staphylococcal cell wall. Accordingly, we
      show that the hyper-spreading phenotype of srtA mutant cells is an indirect
      effect that relates to the sortase substrates FnbpA, FnbpB, ClfA and ClfB. These
      surface-exposed staphylococcal proteins are known to promote biofilm formation,
      and cell-cell interactions. The hyper-spreading phenotype of srtA mutant
      staphylococcal cells was subsequently validated in Staphylococcus epidermidis. We
      conclude that cell wall-associated factors that promote a sessile lifestyle of S.
      aureus and S. epidermidis antagonize the colony spreading motility of these
      bacteria.

PMID- 22970277
TI  - Serum YKL-40 independently predicts outcome after transcatheter arterial
      chemoembolization of hepatocellular carcinoma.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) is the most widely
      used treatment option for unresectable hepatocellular carcinoma (HCC). Elevated
      serum YKL-40 level has been shown to predict poor prognosis in HCC patients
      undergoing resection. This study was designed to validate the prognostic
      significance of serum YKL-40 in patients with HCC undergoing TACE treatment.
      METHODS: Serum YKL-40 level was determined by enzyme-linked immunosorbent assay.
      Overall survival (OS) was evaluated with the Kaplan-Meier method and compared by
      the log-rank test. Multivariate study with Cox proportional hazard model was used
      to evaluate independent prognostic variables of OS. RESULTS: The median
      pretreatment serum YKL-40 in HCC patients with was significantly higher than that
      in healthy controls (P<0.001). The YKL-40 could predict survival precisely either
      in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively).
      Multivariate Cox regression analysis indicated that serum YKL-40 was an
      independent prognostic factor for OS in HCC patients (P = 0.001). In further
      stratified analyses, YKL-40 could discriminate the outcomes of patients with low
      and high alpha-fetoprotein (AFP) level (P = 0.006 and 0.016, respectively).
      Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict
      patients' outcomes. CONCLUSIONS: Serum YKL-40 was demonstrated to be an
      independent prognostic biomarker in HCC patients treated with TACE. Our results
      need confirmation in an independent study.

PMID- 22970278
TI  - Familial hemophagocytic lymphohistiocytosis may present during adulthood:
      clinical and genetic features of a small series.
AB  - Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare immune deficiency
      with defective cytotoxic function. The age at onset is usually young and the
      natural course is rapidly fatal if untreated. A later onset of the disease has
      been sporadically reported even in adolescents and adults. We report the results
      of our retrospective data collection of all cases diagnosed with FHL at an age of
      18 years or older and enrolled in the Italian Registry of HLH. All cases were
      diagnosed with FHL based on evidence of genetic defect in one FHL-related gene. A
      total of 11 patients were diagnosed with FHL. They were 9 males and 2 females,
      from 10 unrelated families; their age ranged between 18 and 43 years (median, 23
      years). Family history was unremarkable in eight families at the time of the
      diagnosis. Their genetic diagnoses are: FHL2 (n = 6), FHL3 (n = 2), FHL5 (n = 1),
      XLP1 (n = 2). Clinical, molecular and functional data are described. These data
      confirm that FHL may present beyond the pediatric age and up to the fifth decade.
      FHL2 due to perforin defect is the most frequently reported subtype. Adult
      specialists should consider FHL in the differential diagnosis of patients with
      cytopenia and liver or central nervous system disorders, especially when a
      lymphoproliferative disease is suspected but eventually not confirmed. FHL may
      turn to be fatal within a short time course even in adults. This risk, together
      with the continuous improvement in the transplant technique, especially in the
      area of transplant from matched unrelated donor, resulting in reduced treatment
      related mortality, might suggest a wider use of SCT in this population. Current
      diagnostic approach allows prompt identification of patients by flow-cytometry
      screening, then confirmed by the genetic study, and treatment with chemo
      immunotherapy followed by stem cell transplantation.

PMID- 22970279
TI  - The early life history of the clam Macoma balthica in a high CO2 world.
AB  - This study investigated the effects of experimentally manipulated seawater
      carbonate chemistry on several early life history processes of the Baltic tellin
      (Macoma balthica), a widely distributed bivalve that plays a critical role in the
      functioning of many coastal habitats. We demonstrate that ocean acidification
      significantly depresses fertilization, embryogenesis, larval development and
      survival during the pelagic phase. Fertilization and the formation of a D-shaped
      shell during embryogenesis were severely diminished: successful fertilization was
      reduced by 11% at a 0.6 pH unit decrease from present (pH 8.1) conditions, while
      hatching success was depressed by 34 and 87%, respectively at a 0.3 and 0.6 pH
      unit decrease. Under acidified conditions, larvae were still able to develop a
      shell during the post-embryonic phase, but higher larval mortality rates indicate
      that fewer larvae may metamorphose and settle in an acidified ocean. The
      cumulative impact of decreasing seawater pH on fertilization, embryogenesis and
      survival to the benthic stage is estimated to reduce the number of competent
      settlers by 38% for a 0.3 pH unit decrease, and by 89% for a 0.6 pH unit decrease
      from present conditions. Additionally, slower growth rates and a delayed
      metamorphosis at a smaller size were indicative for larvae developed under
      acidified conditions. This may further decline the recruit population size due to
      a longer subjection to perturbations, such as predation, during the pelagic
      phase. In general, early life history processes were most severely compromised at
      ~pH 7.5, which corresponds to seawater undersaturated with respect to aragonite.
      Since recent models predict a comparable decrease in pH in coastal waters in the
      near future, this study indicates that future populations of Macoma balthica are
      likely to decline as a consequence of ongoing ocean acidification.

PMID- 22970280
TI  - Transcriptional and epigenetic regulation of KIAA1199 gene expression in human
      breast cancer.
AB  - Emerging evidence has demonstrated that upregulated expression of KIAA1199 in
      human cancer bodes for poor survival. The regulatory mechanism controlling
      KIAA1199 expression in cancer remains to be characterized. In the present study,
      we have isolated and characterized the human KIAA1199 promoter in terms of
      regulation of KIAA1199 gene expression. A 3.3 kb fragment of human genomic DNA
      containing the 5'-flanking sequence of the KIAA1199 gene possesses both
      suppressive and activating elements. Employing a deletion mutagenesis approach, a
      1.4 kb proximal region was defined as the basic KIAA1199 promoter containing a
      TATA-box close to the transcription start site. A combination of 5'-primer
      extension study with 5'RACE DNA sequencing analysis revealed one major
      transcription start site that is utilized in the human KIAA1199 gene.
      Bioinformatics analysis suggested that the 1.4 kb KIAA1199 promoter contains
      putative activating regulatory elements, including activator protein-1(AP-1),
      Twist-1, and NF-kappaB sites. Sequential deletion and site-direct mutagenesis
      analysis demonstrated that the AP-1 and distal NF-kappaB sites are required for
      KIAA1199 gene expression. Further analyses using an electrophoretic mobility
      shift assay and chromatin immunoprecipitation confirmed the requirement of these
      cis- and trans-acting elements in controlling KIAA1199 gene expression. Finally,
      we found that upregulated KIAA1199 expression in human breast cancer specimens
      correlated with hypomethylation of the regulatory region. Involvement of DNA
      methylation in regulation of KIAA1199 expression was recapitulated in human
      breast cancer cell lines. Taken together, our study unraveled the regulatory
      mechanisms controlling KIAA1199 gene expression in human cancer.

PMID- 22970282
TI  - Handed foraging behavior in scale-eating cichlid fish: its potential role in
      shaping morphological asymmetry.
AB  - Scale-eating cichlid fish, Perissodus microlepis, from Lake Tanganyika display
      handed (lateralized) foraging behavior, where an asymmetric 'left' mouth morph
      preferentially feeds on the scales of the right side of its victim fish and a
      'right' morph bites the scales of the left side. This species has therefore
      become a textbook example of the astonishing degree of ecological specialization
      and negative frequency-dependent selection. We investigated the strength of
      handedness of foraging behavior as well as its interaction with morphological
      mouth laterality in P. microlepis. In wild-caught adult fish we found that mouth
      laterality is, as expected, a strong predictor of their preferred attack
      orientation. Also laboratory-reared juvenile fish exhibited a strong laterality
      in behavioral preference to feed on scales, even at an early age, although the
      initial level of mouth asymmetry appeared to be small. This suggests that
      pronounced mouth asymmetry is not a prerequisite for handed foraging behavior in
      juvenile scale-eating cichlid fish and might suggest that behavioral preference
      to attack a particular side of the prey plays a role in facilitating
      morphological asymmetry of this species.

PMID- 22970281
TI  - Borna disease virus infection perturbs energy metabolites and amino acids in
      cultured human oligodendroglia cells.
AB  - BACKGROUND: Borna disease virus is a neurotropic, non-cytolytic virus that has
      been widely employed in neuroscientific research. Previous studies have revealed
      that metabolic perturbations are associated with Borna disease viral infection.
      However, the pathophysiological mechanism underlying its mode of action remains
      unclear. METHODOLOGY: Human oligodendroglia cells infected with the human strain
      Borna disease virus Hu-H1 and non-infected matched control cells were cultured in
      vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based
      metabonomic approach was used to differentiate the metabonomic profiles of 28
      independent intracellular samples from Borna disease virus-infected cells (n =
      14) and matched control cells (n = 14). Partial least squares discriminant
      analysis was performed to demonstrate that the whole metabonomic patterns enabled
      discrimination between the two groups, and further statistical testing was
      applied to determine which individual metabolites displayed significant
      differences between the two groups. FINDINGS: Metabonomic profiling revealed
      perturbations in 23 metabolites, 19 of which were deemed individually
      significant: nine energy metabolites (alpha-glucose, acetate, choline, creatine,
      formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate)
      and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine,
      isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares
      discriminant analysis demonstrated that the whole metabolic patterns enabled
      statistical discrimination between the two groups. CONCLUSION: Borna disease
      viral infection perturbs the metabonomic profiles of several metabolites in human
      oligodendroglia cells cultured in vitro. The findings suggest that Borna disease
      virus manipulates the host cell's metabolic network to support viral replication
      and proliferation.

PMID- 22970283
TI  - Emergence of HGF/SF-induced coordinated cellular motility.
AB  - Collective cell migration plays a major role in embryonic morphogenesis, tissue
      remodeling, wound repair and cancer invasion. Despite many decades of extensive
      investigations, only few analytical tools have been developed to enhance the
      biological understanding of this important phenomenon. Here we present a novel
      quantitative approach to analyze long term kinetics of bright field time-lapse
      wound healing. Fully-automated spatiotemporal measures and visualization of
      cells' motility and implicit morphology were proven to be sound, repetitive and
      highly informative compared to single-cell tracking analysis. We study cellular
      collective migration induced by tyrosine kinase-growth factor signaling (Met
      Hepatocyte Growth Factor/Scatter Factor (HGF/SF)). Our quantitative approach is
      applied to demonstrate that collective migration of the adenocarcinoma cell lines
      is characterized by simple morpho-kinetics. HGF/SF induces complex morpho-kinetic
      coordinated collective migration: cells at the front move faster and are more
      spread than those further away from the wound edge. As the wound heals, distant
      cells gradually accelerate and enhance spread and elongation -resembling the
      epithelial to mesenchymal transition (EMT), and then the cells become more spread
      and maintain higher velocity than cells located closer to the wound. Finally,
      upon wound closure, front cells halt, shrink and round up (resembling mesenchymal
      to epithelial transition (MET) phenotype) while distant cells undergo the same
      process gradually. Met inhibition experiments further validate that Met signaling
      dramatically alters the morpho-kinetic dynamics of the healing wound. Machine
      learning classification was applied to demonstrate the generalization of our
      findings, revealing even subtle changes in motility patterns induced by Met
      inhibition. It is concluded that activation of Met-signaling induces an
      elaborated model in which cells lead a coordinated increased motility along with
      gradual differentiation-based collective cell motility dynamics. Our quantitative
      phenotypes may guide future investigation on the molecular and cellular
      mechanisms of tyrosine kinase-induced coordinate cell motility and morphogenesis
      in metastasis.

PMID- 22970284
TI  - Controlling effects of irradiance and heterotrophy on carbon translocation in the
      temperate coral Cladocora caespitosa.
AB  - Temperate symbiotic corals, such as the Mediterranean species Cladocora
      caespitosa, live in seasonally changing environments, where irradiance can be ten
      times higher in summer than winter. These corals shift from autotrophy in summer
      to heterotrophy in winter in response to light limitation of the symbiont's
      photosynthesis. In this study, we determined the autotrophic carbon budget under
      different conditions of irradiance (20 and 120 umol photons m(-2) s(-1)) and
      feeding (fed three times a week with Artemia salina nauplii, and unfed). Corals
      were incubated in H(13)CO(3) (-)-enriched seawater, and the fate of (13)C was
      followed in the symbionts and the host tissue. The total amount of carbon fixed
      by photosynthesis and translocated was significantly higher at high than low
      irradiance (ca. 13 versus 2.5-4.5 ug cm(-2) h(-1)), because the rates of
      photosynthesis and carbon fixation were also higher. However, the percent of
      carbon translocation was similar under the two irradiances, and reached more than
      70% of the total fixed carbon. Host feeding induced a decrease in the percentage
      of carbon translocated under low irradiance (from 70 to 53%), and also a decrease
      in the rates of carbon translocation per symbiont cell under both irradiances.
      The fate of autotrophic and heterotrophic carbon differed according to
      irradiance. At low irradiance, autotrophic carbon was mostly respired by the host
      and the symbionts, and heterotrophic feeding led to an increase in host biomass.
      Under high irradiance, autotrophic carbon was both respired and released as
      particulate and dissolved organic carbon, and heterotrophic feeding led to an
      increase in host biomass and symbiont concentration. Overall, the maintenance of
      high symbiont concentration and high percentage of carbon translocation under low
      irradiance allow this coral species to optimize its autotrophic carbon
      acquisition, when irradiance conditions are not favourable to photosynthesis.

PMID- 22970285
TI  - Disturbed Ca2+ homeostasis increases glutaminyl cyclase expression; connecting
      two early pathogenic events in Alzheimer's disease in vitro.
AB  - A major neuropathological hallmark of Alzheimer's disease (AD) is the deposition
      of aggregated beta amyloid (Abeta) peptide in the senile plaques. Abeta is a
      peptide of 38-43 amino acids and its accumulation and aggregation plays a key
      role early in the disease. A large fraction of beta amyloid is N-terminally
      truncated rendering a glutamine that can subsequently be cyclized into
      pyroglutamate (pE). This makes the peptide more resistant to proteases, more
      prone to aggregation and increases its neurotoxicity. The enzyme glutaminyl
      cyclase (QC) catalyzes this conversion of glutamine to pE. In brains of AD
      patients, the expression of QC is increased in the earliest stages of pathology,
      which may be an important event in the pathogenesis. In this study we aimed to
      investigate the regulatory mechanism underlying the upregulation of QC expression
      in AD. Using differentiated SK-N-SH as a neuronal cell model, we found that
      neither the presence of Abeta peptides nor the unfolded protein response, two
      early events in AD, leads to increased QC levels. In contrast, we demonstrated
      increased QC mRNA levels and enzyme activity in response to another pathogenic
      factor in AD, perturbed intracellular Ca(2+) homeostasis. The QC promoter
      contains a putative binding site for the Ca(2+) dependent transcription factors c
      fos and c-jun. C-fos and c-jun are induced by the same Ca(2+)-related stimuli as
      QC and their upregulation precedes QC expression. We show that in the human brain
      QC is predominantly expressed by neurons. Interestingly, the Ca(2+)- dependent
      regulation of both c-fos and QC is not observed in non-neuronal cells. Our
      results indicate that perturbed Ca(2+) homeostasis results in upregulation of QC
      selectively in neuronal cells via Ca(2+)- dependent transcription factors. This
      suggests that disruption of Ca(2+) homeostasis may contribute to the formation of
      the neurotoxic pE Abeta peptides in Alzheimer's disease.

PMID- 22970286
TI  - Some novel insights on HPV16 related cervical cancer pathogenesis based on
      analyses of LCR methylation, viral load, E7 and E2/E4 expressions.
AB  - This study was undertaken to decipher the interdependent roles of (i) methylation
      within E2 binding site I and II (E2BS-I/II) and replication origin (nt 7862) in
      the long control region (LCR), (ii) expression of viral oncogene E7, (iii)
      expression of the transcript (E7-E1/E4) that encodes E2 repressor protein and
      (iv) viral load, in human papillomavirus 16 (HPV16) related cervical cancer
      (CaCx) pathogenesis. The results revealed over-representation (p<0.001) of
      methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2
      disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of
      methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases
      than E2-disrupted cases and lack of methylation at replication origin in case of
      both. The viral transcript (E7-E1/E4) that produces the repressor E2 was analyzed
      by APOT (amplification of papillomavirus oncogenic transcript)-coupled
      quantitative-RT-PCR (of E7 and E4 genes) to distinguish episomal (pure or
      concomitant with integrated) from purely integrated viral genomes based on the
      ratio, E7 C(T)/E4 C(T). Relative quantification based on comparative C(T)
      (threshold cycle) method revealed 75.087 folds higher E7 mRNA expression in
      episomal cases over purely integrated cases. Viral load and E2 gene copy numbers
      were negatively correlated with E7 C(T) (p = 0.007) and E2 C(T) (p<0.0001),
      respectively, each normalized with ACTB C(T), among episomal cases only. The k
      means clustering analysis considering E7 C(T) from APOT-coupled-quantitative-RT
      PCR assay, in conjunction with viral load, revealed immense heterogeneity among
      the HPV16 positive CaCx cases portraying integrated viral genomes. The findings
      provide novel insights into HPV16 related CaCx pathogenesis and highlight that
      CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be
      distinct biologically, from the purely integrated viral genomes in terms of host
      genes and/or pathways involved in cervical carcinogenesis.

PMID- 22970287
TI  - Centromeres cluster de novo at the beginning of meiosis in Brachypodium
      distachyon.
AB  - In most eukaryotes that have been studied, the telomeres cluster into a bouquet
      early in meiosis, and in wheat and its relatives and in Arabidopsis the
      centromeres pair at the same time. In Arabidopsis, the telomeres do not cluster
      as a typical telomere bouquet on the nuclear membrane but are associated with the
      nucleolus both somatically and at the onset of meiosis. We therefore assessed
      whether Brachypodium distachyon, a monocot species related to cereals and whose
      genome is approximately twice the size of Arabidopsis thaliana, also exhibited an
      atypical telomere bouquet and centromere pairing. In order to investigate the
      occurrence of a bouquet and centromere pairing in B distachyon, we first had to
      establish protocols for studying meiosis in this species. This enabled us to
      visualize chromosome behaviour in meiocytes derived from young B distachyon
      spikelets in three-dimensions by fluorescent in situ hybridization (FISH), and
      accurately to stage meiosis based on chromatin morphology in relation to spikelet
      size and the timing of sample collection. Surprisingly, this study revealed that
      the centromeres clustered as a single site at the same time as the telomeres also
      formed a bouquet or single cluster.

PMID- 22970288
TI  - Synergistic suppression of early phase of adipogenesis by microsomal PGE synthase
      1 (PTGES1)-produced PGE2 and aldo-keto reductase 1B3-produced PGF2alpha.
AB  - We recently reported that aldo-keto reductase 1B3-produced prostaglandin (PG)
      F(2alpha) suppressed the early phase of adipogenesis. PGE(2) is also known to
      suppress adipogenesis. In this study, we found that microsomal PGE(2) synthase
      (PGES)-1 (mPGES-1; PTGES1) acted as the PGES in adipocytes and that PGE(2) and
      PGF(2alpha) synergistically suppressed the early phase of adipogenesis. PGE(2)
      production was detected in preadipocytes and transiently enhanced at 3 h after
      the initiation of adipogenesis of mouse adipocytic 3T3-L1 cells, followed by a
      quick decrease; and its production profile was similar to the expression of the
      cyclooxygenase-2 (PTGS2) gene. When 3T3-L1 cells were transfected with siRNAs for
      any one of the three major PTGESs, i.e., PTGES1, PTGES2 (mPGES-2), and PTGES3
      (cytosolic PGES), only PTGES1 siRNA suppressed PGE(2) production and enhanced the
      expression of adipogenic genes. AE1-329, a PTGER4 (EP4) receptor agonist,
      increased the expression of the Ptgs2 gene with a peak at 1 h after the
      initiation of adipogenesis. PGE(2)-mediated enhancement of the PTGS2 expression
      was suppressed by the co-treatment with L-161982, a PTGER4 receptor antagonist.
      Moreover, AE1-329 enhanced the expression of the Ptgs2 gene by binding of the
      cyclic AMP response element (CRE)-binding protein to the CRE of the Ptgs2
      promoter; and its binding was suppressed by co-treatment with L-161982, which was
      demonstrated by promoter luciferase and chromatin immunoprecipitation assays.
      Furthermore, when 3T3-L1 cells were caused to differentiate into adipocytes in
      medium containing both PGE(2) and PGF(2alpha), the expression of the adipogenic
      genes and the intracellular triglyceride level were decreased to a greater extent
      than in medium containing either of them, revealing that PGE(2) and PGF(2alpha)
      independently suppressed adipogenesis. These results indicate that PGE(2) was
      synthesized by PTGES1 in adipocytes and synergistically suppressed the early
      phase of adipogenesis of 3T3-L1 cells in cooperation with PGF(2alpha) through
      receptor-mediated activation of PTGS2 expression.

PMID- 22970290
TI  - Altered protein expression in gestational diabetes mellitus placentas provides
      insight into insulin resistance and coagulation/fibrinolysis pathways.
AB  - OBJECTIVE: To investigate the placental proteome differences between pregnant
      women complicated with gestational diabetes mellitus (GDM) and those with normal
      glucose tolerance (NGT). METHODS: We used two-dimensional electrophoresis (2DE)
      to separate and compare placental protein levels from GDM and NGT groups.
      Differentially expressed proteins between the two groups were identified by MALDI
      TOF/TOF mass spectrometry and further confirmed by Western blotting. The mRNA
      levels of related proteins were measured by realtime RT-PCR. Immunohistochemistry
      (IHC) was performed to examine the cellular location of the proteins expressed in
      placenta villi. RESULTS: Twenty-one protein spots were differentially expressed
      between GDM and NGT placenta villi in the tested samples, fifteen of which were
      successfully identified by mass spectrometry. The molecular functions of these
      differentially expressed proteins include blood coagulation, signal transduction,
      anti-apoptosis, ATP binding, phospholipid binding, calcium ion binding, platelet
      activation, and tryptophan-tRNA ligase activity. Both protein and mRNA levels of
      Annexin A2, Annexin A5 and 14-3-3 protein zeta/delta were up-regulated, while the
      expression of the Ras-related protein Rap1A was down-regulated in the GDM
      placenta group. CONCLUSION: Placenta villi derived from GDM pregnant women
      exhibit significant proteome differences compared to those of NGT mothers. The
      identified differentially expressed proteins are mainly associated with the
      development of insulin resistance, transplacental transportation of glucose,
      hyperglucose-mediated coagulation and fibrinolysis disorders in the GDM placenta
      villi.

PMID- 22970291
TI  - Thermal and structural behavior of dioctadecyldimethylammonium bromide
      dispersions studied by differential scanning calorimetry and X-ray scattering.
AB  - Dioctadecyldimethylammonium bromide (DODAB) is a double chain cationic lipid,
      which assembles as bilayer structures in aqueous solution. The precise structures
      formed depend on, e.g., lipid concentration and temperature. We here combine
      differential scanning calorimetry (DSC) and X-ray scattering (SAXS and WAXS) to
      investigate the thermal and structural behavior of up to 120 mM DODAB in water
      within the temperature range 1-70  degrees C. Below 1 mM, this system is
      dominated by unilamellar vesicles (ULVs). Between 1 and 65 mM, ULVs and
      multilamellar structures (MLSs) co-exist, while above 65 mM, the MLSs are the
      preferred structure. Depending on temperature, DSC and X-ray data show that the
      vesicles can be either in the subgel (SG), gel, or liquid crystalline (LC) state,
      while the MLSs (with lattice distance d = 36.7 A) consist of interdigitated
      lamellae in the SG state, and ULVs in the LC state (no Bragg peak). Critical
      temperatures related to the thermal transitions of these bilayer structures
      obtained in the heating and cooling modes are reported, together with the
      corresponding transition enthalpies.

PMID- 22970289
TI  - Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied
      and -untied toxicity mechanisms common to neurodegenerative diseases.
AB  - The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I,
      and destabilizes microtubules (MT) has been linked to Parkinson disease (PD)
      etiology and is often used to model this neurodegenerative disease (ND). Many of
      the mechanisms of action of rotenone are posited mechanisms of neurodegeneration;
      however, they are not fully understood. Therefore, the study of rotenone-affected
      functional pathways is pertinent to the understanding of NDs pathogenesis. This
      report describes the transcriptome analysis of a neuroblastoma (NB) cell line
      chronically exposed to marginally toxic and moderately toxic doses of rotenone.
      The results revealed a complex pleiotropic response to rotenone that impacts a
      variety of cellular events, including cell cycle, DNA damage response,
      proliferation, differentiation, senescence and cell death, which could lead to
      survival or neurodegeneration depending on the dose and time of exposure and cell
      phenotype. The response encompasses an array of physiological pathways, modulated
      by transcriptional and epigenetic regulatory networks, likely activated by
      homeostatic alterations. Pathways that incorporate the contribution of MT
      destabilization to rotenone toxicity are suggested to explain complex I
      independent rotenone-induced alterations of metabolism and redox homeostasis. The
      postulated mechanisms involve the blockage of mitochondrial voltage-dependent
      anions channels (VDACs) by tubulin, which coupled with other rotenone-induced
      organelle dysfunctions may underlie many presumed neurodegeneration mechanisms
      associated with pathophysiological aspects of various NDs including PD, AD and
      their variant forms. Thus, further investigation of such pathways may help
      identify novel therapeutic paths for these NDs.

PMID- 22970292
TI  - Identification of the Kelch family protein Nd1-L as a novel molecular interactor
      of KRIT1.
AB  - Loss-of-function mutations of the KRIT1 gene (CCM1) have been associated with the
      Cerebral Cavernous Malformation (CCM) disease, which is characterized by serious
      alterations of brain capillary architecture. The KRIT1 protein contains multiple
      interaction domains and motifs, suggesting that it might act as a scaffold for
      the assembly of functional protein complexes involved in signaling networks. In
      previous work, we defined structure-function relationships underlying KRIT1
      intramolecular and intermolecular interactions and nucleocytoplasmic shuttling,
      and found that KRIT1 plays an important role in molecular mechanisms involved in
      the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to
      prevent oxidative cellular damage. Here we report the identification of the Kelch
      family protein Nd1-L as a novel molecular interactor of KRIT1. This interaction
      was discovered through yeast two-hybrid screening of a mouse embryo cDNA library,
      and confirmed by pull-down and co-immunoprecipitation assays of recombinant
      proteins, as well as by co-immunoprecipitation of endogenous proteins in human
      endothelial cells. Furthermore, using distinct KRIT1 isoforms and mutants, we
      defined the role of KRIT1 domains in the Nd1-L/KRIT1 interaction. Finally,
      functional assays showed that Nd1-L may contribute to the regulation of KRIT1
      nucleocytoplasmic shuttling and cooperate with KRIT1 in modulating the expression
      levels of the antioxidant protein SOD2, opening a novel avenue for future
      mechanistic studies. The identification of Nd1-L as a novel KRIT1 interacting
      protein provides a novel piece of the molecular puzzle involving KRIT1 and
      suggests a potential functional cooperation in cellular responses to oxidative
      stress, thus expanding the framework of molecular complexes and mechanisms that
      may underlie the pathogenesis of CCM disease.

PMID- 22970294
TI  - Post-translational processing of synaptophysin in the rat retina is disrupted by
      diabetes.
AB  - Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle
      recycling and neurotransmitter release. Previous work shows that its content is
      significantly reduced in the rat retina by streptozotocin (STZ)-diabetes. This
      study tested the hypothesis that STZ-diabetes alters synaptophysin protein
      turnover and glycosylation in the rat retina. Whole explant retinas from male
      Sprague-Dawley rats were used in this study. Rats were made diabetic by a single
      intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH
      4.5). mRNA translation was measured using a (35)S-methionine labeling assay
      followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase
      study was used to determine the depletion of newly synthesized synaptophysin.
      Depletion of total synaptophysin was determined after treatment with
      cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating
      retinal lysates with endoglycosidase H followed by immunoblot analysis.
      Synaptophysin mRNA translation was significantly increased after 1 month
      (p<0.001) and 2 months (p<0.05) of STZ-diabetes, compared to age-matched
      controls. Newly synthesized synaptophysin degradation was significantly
      accelerated in the retina after 1 and 2 months of diabetes compared to controls
      (p<0.05). Mannose rich glycosylated synaptophysin was significantly increased
      after 1 month of STZ-diabetes compared to controls (p<0.05).These data suggest
      that diabetes increases mRNA translation of synaptophysin in the retina,
      resulting in an accumulation of mannose rich glycosylated synaptophysin, a
      transient post-translational state of the protein. This diabetes-induced
      irregularity in post-translational processing could explain the accelerated
      degradation of retinal synaptophysin in diabetes.

PMID- 22970293
TI  - A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by
      dendritic cells from soluble tumor antigen.
AB  - NY-ESO-1 has been a major target of many immunotherapy trials because it is
      expressed by various cancers and is highly immunogenic. In this study, we have
      identified a novel HLA-B*1801-restricted CD8(+) T cell epitope, NY-ESO-1(88-96)
      (LEFYLAMPF) and compared its direct- and cross-presentation to that of the
      reported NY-ESO-1(157-165) epitope restricted to HLA-A*0201. Although both
      epitopes were readily cross-presented by DCs exposed to various forms of full
      length NY-ESO-1 antigen, remarkably NY-ESO-1(88-96) is much more efficiently
      cross-presented from the soluble form, than NY-ESO-1(157-165). On the other hand,
      NY-ESO-1(157-165) is efficiently presented by NY-ESO-1-expressing tumor cells and
      its presentation was not enhanced by IFN-gamma treatment, which induced
      immunoproteasome as demonstrated by Western blots and functionally a decreased
      presentation of Melan A(26-35); whereas NY-ESO-1(88-96) was very inefficiently
      presented by the same tumor cell lines, except for one that expressed high level
      of immunoproteasome. It was only presented when the tumor cells were first IFN
      gamma treated, followed by infection with recombinant vaccinia virus encoding NY
      ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that
      the presentation of NY-ESO-1(88-96) is immunoproteasome dependent. Furthermore, a
      survey was conducted on multiple samples collected from HLA-B18(+) melanoma
      patients. Surprisingly, all the detectable responses to NY-ESO-1(88-96) from
      patients, including those who received NY-ESO-1 ISCOMATRIXTM vaccine were induced
      spontaneously. Taken together, these results imply that some epitopes can be
      inefficiently presented by tumor cells although the corresponding CD8(+) T cell
      responses are efficiently primed in vivo by DCs cross-presenting these epitopes.
      The potential implications for cancer vaccine strategies are further discussed.

PMID- 22970295
TI  - Re-emergence of the apicomplexan Theileria equi in the United States: elimination
      of persistent infection and transmission risk.
AB  - Arthropod-borne apicomplexan pathogens that cause asymptomatic persistent
      infections present a significant challenge due to their life-long transmission
      potential. Although anti-microbials have been used to ameliorate acute disease in
      animals and humans, chemotherapeutic efficacy for apicomplexan pathogen
      elimination from a persistently infected host and removal of transmission risk is
      largely unconfirmed. The recent re-emergence of the apicomplexan Theileria equi
      in U.S. horses prompted testing whether imidocarb dipropionate was able to
      eliminate T. equi from naturally infected horses and remove transmission risk.
      Following imidocarb treatment, levels of T. equi declined from a mean of 10(4.9)
      organisms/ml of blood to undetectable by nested PCR in 24 of 25 naturally
      infected horses. Further, blood transfer from treated horses that became nested
      PCR negative failed to transmit to naive splenectomized horses. Although these
      results were consistent with elimination of infection in 24 of 25 horses, T. equi
      specific antibodies persisted in the majority of imidocarb treated horses.
      Imidocarb treatment was unsuccessful in one horse which remained infected as
      measured by nested PCR and retained the ability to infect a naive recipient via
      intravenous blood transfer. However, a second round of treatment eliminated T.
      equi infection. These results support the utility of imidocarb chemotherapy for
      assistance in the control and eradication of this tick-borne pathogen. Successful
      imidocarb dipropionate treatment of persistently infected horses provides a tool
      to aid the global equine industry by removing transmission risk associated with
      infection and facilitating international movement of equids between endemic and
      non-endemic regions.

PMID- 22970296
TI  - Metabolic rate regulates L1 longevity in C. elegans.
AB  - Animals have to cope with starvation. The molecular mechanisms by which animals
      survive long-term starvation, however, are not clearly understood. When they
      hatch without food, C. elegans arrests development at the first larval stage (L1)
      and survives more than two weeks. Here we show that the survival span of arrested
      L1s, which we call L1 longevity, is a starvation response regulated by metabolic
      rate during starvation. A high rate of metabolism shortens the L1 survival span,
      whereas a low rate of metabolism lengthens it. The longer worms are starved, the
      slower they grow once they are fed, suggesting that L1 arrest has metabolic
      costs. Furthermore, mutants of genes that regulate metabolism show altered L1
      longevity. Among them, we found that AMP-dependent protein kinase (AMPK), as a
      key energy sensor, regulates L1 longevity by regulating this metabolic arrest.
      Our results suggest that L1 longevity is determined by metabolic rate and that
      AMPK as a master regulator of metabolism controls this arrest so that the animals
      survive long-term starvation.

PMID- 22970297
TI  - Does it really matter where you look when walking on stairs? Insights from a dual
      task study.
AB  - Although the visual system is known to provide relevant information to guide
      stair locomotion, there is less understanding of the specific contributions of
      foveal and peripheral visual field information. The present study investigated
      the specific role of foveal vision during stair locomotion and ground-stairs
      transitions by using a dual-task paradigm to influence the ability to rely on
      foveal vision. Fifteen healthy adults (26.9 +/- 3.3 years; 8 females) ascended a
      7-step staircase under four conditions: no secondary tasks (CONTROL); gaze
      fixation on a fixed target located at the end of the pathway (TARGET); visual
      reaction time task (VRT); and auditory reaction time task (ART). Gaze fixations
      towards stair features were significantly reduced in TARGET and VRT compared to
      CONTROL and ART. Despite the reduced fixations, participants were able to
      successfully ascend stairs and rarely used the handrail. Step time was increased
      during VRT compared to CONTROL in most stair steps. Navigating on the transition
      steps did not require more gaze fixations than the middle steps. However,
      reaction time tended to increase during locomotion on transitions suggesting
      additional executive demands during this phase. These findings suggest that
      foveal vision may not be an essential source of visual information regarding
      stair features to guide stair walking, despite the unique control challenges at
      transition phases as highlighted by phase-specific challenges in dual-tasking.
      Instead, the tendency to look at the steps in usual conditions likely provides a
      stable reference frame for extraction of visual information regarding step
      features from the entire visual field.

PMID- 22970299
TI  - Identification of paleo-events recorded in the yellow sea sediments by sorting
      coefficient of grain size.
AB  - Identification of natural and anthropogenic events in the past is important for
      studying their patterns and mechanisms; and sensitive proxies in marine sediments
      are more reliable for identifying these events than those in terrestrial
      sediments, which are usually disturbed by human activities. Since the main source
      materials for the sediments in the Northern Yellow Sea Mud are transported by the
      Yellow River, sedimentary characteristics can be used to reconstruct the
      historical events that occurred in the Yellow River Valley. In the present study,
      by analyzing sorting coefficient of grain size in a 250-year sediment core from
      the Northern Yellow Sea Mud, we identified several major historical events: the
      Haiyuan Earthquake in AD 1920 and several times of relocation of the Yellow River
      estuary. The proxy has the potential of detecting and reconstructing historical
      events; in combination with historical archives, they also provide an accurate
      dating method.

PMID- 22970298
TI  - Blocking retinal chloride co-transporters KCC2 and NKCC: impact on direction
      selective ON and OFF responses in the rat's nucleus of the optic tract.
AB  - In the present study we investigated in vivo the effects of pharmacological
      manipulation of retinal processing on the response properties of direction
      selective retinal slip cells in the nucleus of the optic tract and dorsal
      terminal nucleus (NOT-DTN), the key visuomotor interface in the pathway
      underlying the optokinetic reflex. Employing a moving visual stimulus consisting
      of either a large dark or light edge we could differentiate direction selective
      ON and OFF responses in retinal slip cells. To disclose the origin of the retinal
      slip cells' unexpected OFF response we selectively blocked the retinal ON
      channels and inactivated the visual cortex by cooling. Cortical cooling had no
      effect on the direction selectivity of the ON or the OFF response in NOT-DTN
      retinal slip cells. Blockade of the retinal ON channel with APB led to a loss of
      the ON and, to a lesser degree, of the OFF response and a reduction in direction
      selectivity. Subsequent blocking of GABA receptors in the retina with picrotoxin
      unmasked a vigorous albeit direction unselective OFF response in the NOT-DTN.
      Disturbing the retinal chloride homeostasis by intraocular injections of
      bumetanide or furosemide led to a loss of direction selectivity in both the NOT
      DTN's ON and the OFF response due to a reduced response in the neuron's preferred
      direction under bumetanide as well as under furosemide and a slightly increased
      response in the null direction under bumetanide. Our results indicate that the
      direction specificity of retinal slip cells in the NOT-DTN of the rat strongly
      depends on direction selective retinal input which depends on intraretinal
      chloride homeostasis. On top of the well established input from ON center
      direction selective ganglion cells we could demonstrate an equally effective
      input from the retinal OFF system to the NOT-DTN.

PMID- 22970300
TI  - Nontypeable Haemophilus influenzae genetic islands associated with chronic
      pulmonary infection.
AB  - BACKGROUND: Haemophilus influenzae (Hi) colonizes the human respiratory tract and
      is an important pathogen associated with chronic obstructive pulmonary disease
      (COPD). Bacterial factors that interact with the human host may be important in
      the pathogenesis of COPD. These factors, however, have not been well defined. The
      overall goal of this study was to identify bacterial genetic elements with
      increased prevalence among H. influenzae strains isolated from patients with COPD
      compared to those isolated from the pharynges of healthy individuals.
      METHODOLOGY/PRINCIPAL FINDINGS: Four nontypeable H. influenzae (NTHi) strains,
      two isolated from the airways of patients with COPD and two from a healthy
      individual, were subjected to whole genome sequencing using 454 FLX Titanium
      technology. COPD strain-specific genetic islands greater than 500 bp in size were
      identified by in silico subtraction. Open reading frames residing within these
      islands include known Hi virulence genes such as lic2b, hgbA, iga, hmw1 and hmw2,
      as well as genes encoding urease and other enzymes involving metabolic pathways.
      The distributions of seven selected genetic islands were assessed among a panel
      of 421 NTHi strains of both disease and commensal origins using a Library-on-a
      Slide high throughput dot blot DNA hybridization procedure. Four of the seven
      islands screened, containing genes that encode a methyltransferase, a
      dehydrogenase, a urease synthesis enzyme, and a set of unknown short ORFs,
      respectively, were more prevalent in COPD strains than in colonizing strains with
      prevalence ratios ranging from 1.21 to 2.85 (p <= 0.0002). Surprisingly, none of
      these sequences show increased prevalence among NTHi isolated from the airways of
      patients with cystic fibrosis. CONCLUSIONS/SIGNIFICANCE: Our data suggest that
      specific bacterial genes, many involved in metabolic functions, are associated
      with the ability of NTHi strains to survive in the lower airways of patients with
      COPD.

PMID- 22970301
TI  - Rottlerin-mediated inhibition of Chlamydia trachomatis growth and uptake of
      sphingolipids is independent of p38-regulated/activated protein kinase (PRAK).
AB  - We previously found that rottlerin, a plant-derived small molecule compound,
      profoundly inhibited Chlamydia trachomatis growth and blocked sphingolipid
      trafficking from host cell Golgi into chlamydial inclusions. Since the p38
      regulated/activated protein kinase (PRAK) is a known target of rottlerin and is
      activated in Chlamydia trachomatis-infected cells, we investigated the potential
      role of this kinase in rottlerin-mediated anti-chlamydial activity. However, we
      found that a PRAK-specific inhibitor failed to inhibit chlamydial growth,
      suggesting that the kinase activity of PRAK may not be required for chlamydial
      intracellular replication. This conclusion was supported by the observation that
      chlamydial organisms replicated equally well in mouse embryonic fibroblast cells
      with or without PRAK. Moreover, neither the PRAK inhibitor nor PRAK deficiency
      altered host sphingolipid trafficking into chlamydial inclusions. Finally,
      rottlerin maintained its anti-chlamydial activity in PRAK-deficient cells.
      Together, these observations have demonstrated that PRAK is not required for
      either the rottlerin-mediated anti-chlamydial activity or rottlerin inhibition of
      sphingolipid trafficking, suggesting that rottlerin may achieve its inhibitory
      role by targeting other host factors.

PMID- 22970302
TI  - The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug
      resistance.
AB  - The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal
      morphogenesis, biofilm development, drug resistance, and virulence. Hsp90
      functions in concert with co-chaperones to regulate stability and activation of
      client proteins, many of which are signal transducers. Here, we characterize the
      first Hsp90 co-chaperone in the leading human fungal pathogen, Candida albicans.
      We demonstrate that Sgt1 physically interacts with Hsp90, and that it governs C.
      albicans morphogenesis and drug resistance. Genetic depletion of Sgt1 phenocopies
      depletion of Hsp90, inducing yeast to filament morphogenesis and invasive growth.
      Sgt1 governs these traits by bridging two morphogenetic regulators: Hsp90 and the
      adenylyl cyclase of the cAMP-PKA signaling cascade, Cyr1. Sgt1 physically
      interacts with Cyr1, and depletion of either Sgt1 or Hsp90 activates cAMP-PKA
      signaling, revealing the elusive link between Hsp90 and the PKA signaling
      cascade. Sgt1 also mediates tolerance and resistance to the two most widely
      deployed classes of antifungal drugs, azoles and echinocandins. Depletion of Sgt1
      abrogates basal tolerance and acquired resistance to azoles, which target the
      cell membrane. Depletion of Sgt1 also abrogates tolerance and resistance to
      echinocandins, which target the cell wall, and renders echinocandins fungicidal.
      Though Sgt1 and Hsp90 have a conserved impact on drug resistance, the underlying
      mechanisms are distinct. Depletion of Hsp90 destabilizes the client protein
      calcineurin, thereby blocking crucial responses to drug-induced stress; in
      contrast, depletion of Sgt1 does not destabilize calcineurin, but blocks
      calcineurin activation in response to drug-induced stress. Sgt1 influences not
      only morphogenesis and drug resistance, but also virulence, as genetic depletion
      of C. albicans Sgt1 leads to reduced kidney fungal burden in a murine model of
      systemic infection. Thus, our characterization of the first Hsp90 co-chaperone in
      a fungal pathogen establishes C. albicans Sgt1 as a global regulator of
      morphogenesis and drug resistance, providing a new target for treatment of life
      threatening fungal infections.

PMID- 22970303
TI  - Heart of endosymbioses: transcriptomics reveals a conserved genetic program among
      arbuscular mycorrhizal, actinorhizal and legume-rhizobial symbioses.
AB  - To improve their nutrition, most plants associate with soil microorganisms,
      particularly fungi, to form mycorrhizae. A few lineages, including actinorhizal
      plants and legumes are also able to interact with nitrogen-fixing bacteria hosted
      intracellularly inside root nodules. Fossil and molecular data suggest that the
      molecular mechanisms involved in these root nodule symbioses (RNS) have been
      partially recycled from more ancient and widespread arbuscular mycorrhizal (AM)
      symbiosis. We used a comparative transcriptomics approach to identify genes
      involved in establishing these 3 endosymbioses and their functioning. We analysed
      global changes in gene expression in AM in the actinorhizal tree C. glauca. A
      comparison with genes induced in AM in Medicago truncatula and Oryza sativa
      revealed a common set of genes induced in AM. A comparison with genes induced in
      nitrogen-fixing nodules of C. glauca and M. truncatula also made it possible to
      define a common set of genes induced in these three endosymbioses. The existence
      of this core set of genes is in accordance with the proposed recycling of ancient
      AM genes for new functions related to nodulation in legumes and actinorhizal
      plants.

PMID- 22970304
TI  - Motor representation of actions in children with autism.
AB  - BACKGROUND: Children with Autistic Spectrum Disorders (ASD) are frequently
      hampered by motor impairment, with difficulties ranging from imitation of actions
      to recognition of motor intentions. Such a widespread inefficiency of the motor
      system is likely to interfere on the ontogeny of both motor planning and
      understanding of the goals of actions, thus delivering its ultimate effects on
      the emergence of social cognition. METHODOLOGY/PRINCIPAL FINDINGS: We investigate
      the organization of action representation in 15 high functioning ASD (mean age:
      8.11) and in two control samples of typically developing (TD) children: the first
      one, from a primary school, was matched for chronological age (CA), the second
      one, from a kindergarten, comprised children of much younger age (CY). We used
      nine newly designed behavioural motor tasks, aiming at exploring three domains of
      motor cognition: 1) imitation of actions, 2) production of pantomimes, and 3)
      comprehension of pantomimes. The findings reveal that ASD children fare
      significantly worse than the two control samples in each of the inspected
      components of the motor representation of actions, be it the imitation of
      gestures, the self-planning of pantomimes, or the (verbal) comprehension of
      observed pantomimes. In the latter task, owing to its cognitive complexity, ASD
      children come close to the younger TD children's level of performance; yet they
      fare significantly worse with respect to their age-mate controls. Overall, ASD
      children reveal a profound damage to the mechanisms that control both production
      and pre-cognitive "comprehension" of the motor representation of actions.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest that many of the social cognitive
      impairments manifested by ASD individuals are likely rooted in their incapacity
      to assemble and directly grasp the intrinsic goal-related organization of motor
      behaviour. Such impairment of motor cognition might be partly due to an early
      damage of the Mirror Neuron Mechanism (MNM).

PMID- 22970305
TI  - Direct behavioral evidence for retronasal olfaction in rats.
AB  - The neuroscience of flavor perception is becoming increasingly important to
      understand abnormal feeding behaviors and associated chronic diseases such as
      obesity. Yet, flavor research has mainly depended on human subjects due to the
      lack of an animal model. A crucial step towards establishing an animal model of
      flavor research is to determine whether the animal uses the retronasal mode of
      olfaction, an essential element of flavor perception. We designed a go- no go
      behavioral task to test the rat's ability to detect and discriminate retronasal
      odorants. In this paradigm, tasteless aqueous solutions of odorants were licked
      by water-restricted head-fixed rats from a lick spout. Orthonasal contamination
      was avoided by employing a combination of a vacuum around the lick-spout and
      blowing clean air toward the nose. Flow models support the effectiveness of both
      approaches. The licked odorants were successfully discriminated by rats.
      Moreover, the tasteless odorant amyl acetate was reliably discriminated against
      pure distilled water in a concentration-dependent manner. The results from this
      retronasal odor discrimination task suggest that rats are capable of smelling
      retronasally. This direct behavioral evidence establishes the rat as a useful
      animal model for flavor research.

PMID- 22970306
TI  - Aggregation of polyQ proteins is increased upon yeast aging and affected by Sir2
      and Hsf1: novel quantitative biochemical and microscopic assays.
AB  - Aging-related neurodegenerative disorders, such as Parkinson's, Alzheimer's and
      Huntington's diseases, are characterized by accumulation of protein aggregates in
      distinct neuronal cells that eventually die. In Huntington's disease, the protein
      huntingtin forms aggregates, and the age of disease onset is inversely correlated
      to the length of the protein's poly-glutamine tract. Using quantitative assays to
      estimate microscopically and capture biochemically protein aggregates, here we
      study in Saccharomyces cerevisiae aging-related aggregation of GFP-tagged,
      huntingtin-derived proteins with different polyQ lengths. We find that the short
      25Q protein never aggregates whereas the long 103Q version always aggregates.
      However, the mid-size 47Q protein is soluble in young logarithmically growing
      yeast but aggregates as the yeast cells enter the stationary phase and age,
      allowing us to plot an "aggregation timeline". This aging-dependent aggregation
      was associated with increased cytotoxicity. We also show that two aging-related
      genes, SIR2 and HSF1, affect aggregation of the polyQ proteins. In Deltasir2
      strain the aging-dependent aggregation of the 47Q protein is aggravated, while
      overexpression of the transcription factor Hsf1 attenuates aggregation. Thus, the
      mid-size 47Q protein and our quantitative aggregation assays provide valuable
      tools to unravel the roles of genes and environmental conditions that affect
      aging-related aggregation.

PMID- 22970308
TI  - Genetic divergence disclosing a rapid prehistorical dispersion of Native
      Americans in Central and South America.
AB  - An accurate estimate of the divergence time between Native Americans is important
      for understanding the initial entry and early dispersion of human beings in the
      New World. Current methods for estimating the genetic divergence time of
      populations could seriously depart from a linear relationship with the true
      divergence for multiple populations of a different population size and
      significant population expansion. Here, to address this problem, we propose a
      novel measure to estimate the genetic divergence time of populations. Computer
      simulation revealed that the new measure maintained an excellent linear
      correlation with the population divergence time in complicated multi-population
      scenarios with population expansion. Utilizing the new measure and microsatellite
      data of 21 Native American populations, we investigated the genetic divergences
      of the Native American populations. The results indicated that genetic
      divergences between North American populations are greater than that between
      Central and South American populations. None of the divergences, however, were
      large enough to constitute convincing evidence supporting the two-wave or multi
      wave migration model for the initial entry of human beings into America. The
      genetic affinity of the Native American populations was further explored using
      Neighbor-Net and the genetic divergences suggested that these populations could
      be categorized into four genetic groups living in four different ecologic zones.
      The divergence of the population groups suggests that the early dispersion of
      human beings in America was a multi-step procedure. Further, the divergences
      suggest the rapid dispersion of Native Americans in Central and South Americas
      after a long standstill period in North America.

PMID- 22970307
TI  - Potential role of estrogen receptor beta as a tumor suppressor of epithelial
      ovarian cancer.
AB  - Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and
      improvement of treatments is still required. Previous studies have shown that
      Estrogen-receptor beta (ERbeta) levels decreased along with ovarian
      carcinogenesis. Here, we present evidence that reintroduction of ERbeta in BG-1
      epithelial ovarian cancer cells, which express ERalpha, leads in vitro to a
      decrease of basal and estradiol-promoted cell proliferation. ERbeta reduced the
      frequency of cells in S phase and increased the one of cells in G2/M phase. At
      the molecular level, we found that ERbeta downregulated total retinoblastoma
      (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1
      and A2. In addition, ERbeta had a direct effect on ERalpha, by strongly
      inhibiting its expression and activity, which could explain part of the anti
      proliferative action of ERbeta. By developing a novel preclinical model of
      ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice,
      we further revealed that ERbeta expression reduces tumor growth and the presence
      of tumor cells in sites of metastasis, hence resulting in improved survival of
      mice. Altogether, these findings unveil a potential tumor-suppressor role of
      ERbeta in ovarian carcinogenesis, which could be of potential clinical relevance
      for the selection of the most appropriate treatment for patients.

PMID- 22970310
TI  - Developmental changes in emotion recognition from full-light and point-light
      displays of body movement.
AB  - To date, research on the development of emotion recognition has been dominated by
      studies on facial expression interpretation; very little is known about
      children's ability to recognize affective meaning from body movements. In the
      present study, we acquired simultaneous video and motion capture recordings of
      two actors portraying four basic emotions (Happiness Sadness, Fear and Anger).
      One hundred and seven primary and secondary school children (aged 4-17) and 14
      adult volunteers participated in the study. Each participant viewed the full
      light and point-light video clips and was asked to make a forced-choice as to
      which emotion was being portrayed. As a group, children performed worse than
      adults for both point-light and full-light conditions. Linear regression showed
      that both age and lighting condition were significant predictors of performance
      in children. Using piecewise regression, we found that a bilinear model with a
      steep improvement in performance until 8.5 years of age, followed by a much
      slower improvement rate through late childhood and adolescence best explained the
      data. These findings confirm that, like for facial expression, adolescents'
      recognition of basic emotions from body language is not fully mature and seems to
      follow a non-linear development. This is in line with observations of non-linear
      developmental trajectories for different aspects of human stimuli processing
      (voices and faces), perhaps suggesting a shift from one perceptual or cognitive
      strategy to another during adolescence. These results have important implications
      to understanding the maturation of social cognition.

PMID- 22970309
TI  - Host-plant species conservatism and ecology of a parasitoid fig wasp genus
      (Chalcidoidea; Sycoryctinae; Arachonia).
AB  - Parasitoid diversity in terrestrial ecosystems is enormous. However, ecological
      processes underpinning their evolutionary diversification in association with
      other trophic groups are still unclear. Specialisation and interdependencies
      among chalcid wasps that reproduce on Ficus presents an opportunity to
      investigate the ecology of a multi-trophic system that includes parasitoids. Here
      we estimate the host-plant species specificity of a parasitoid fig wasp genus
      that attacks the galls of non-pollinating pteromalid and pollinating agaonid fig
      wasps. We discuss the interactions between parasitoids and the Ficus species
      present in a forest patch of Uganda in context with populations in Southern
      Africa. Haplotype networks are inferred to examine intraspecific mitochondrial
      DNA divergences and phylogenetic approaches used to infer putative species
      relationships. Taxonomic appraisal and putative species delimitation by molecular
      and morphological techniques are compared. Results demonstrate that a parasitoid
      fig wasp population is able to reproduce on at least four Ficus species present
      in a patch. This suggests that parasitoid fig wasps have relatively broad host
      Ficus species ranges compared to fig wasps that oviposit internally. Parasitoid
      fig wasps did not recruit on all available host plants present in the forest
      census area and suggests an important ecological consequence in mitigating
      fitness trade-offs between pollinator and Ficus reproduction. The extent to which
      parasitoid fig wasps exert influence on the pollination mutualism must consider
      the fitness consequences imposed by the ability to interact with phenotypes of
      multiple Ficus and fig wasps species, but not equally across space and time.

PMID- 22970311
TI  - Distinct functional patterns of gene promoter hypomethylation and
      hypermethylation in cancer genomes.
AB  - BACKGROUND: Aberrant DNA methylation plays important roles in carcinogenesis.
      However, the functional significance of genome-wide hypermethylation and
      hypomethylation of gene promoters in carcinogenesis currently remain unclear.
      PRINCIPAL FINDINGS: Based on genome-wide methylation data for five cancer types,
      we showed that genes with promoter hypermethylation were highly consistent in
      function across different cancer types, and so were genes with promoter
      hypomethylation. Functions related to "developmental processes" and "regulation
      of biology processes" were significantly enriched with hypermethylated genes but
      were depleted of hypomethylated genes. In contrast, functions related to "cell
      killing" and "response to stimulus", including immune and inflammatory response,
      were associated with an enrichment of hypomethylated genes and depletion of
      hypermethylated genes. We also observed that some families of cytokines secreted
      by immune cells, such as IL10 family cytokines and chemokines, tended to be
      hypomethylated in various cancer types. These results provide new hints for
      understanding the distinct functional roles of genome-wide hypermethylation and
      hypomethylation of gene promoters in carcinogenesis. CONCLUSIONS: Genes with
      promoter hypermethylation and hypomethylation are highly consistent in function
      across different cancer types, respectively, but these two groups of genes tend
      to be enriched in different functions associated with cancer. Especially, we
      speculate that hypomethylation of gene promoters may play roles in inducing
      immunity and inflammation disorders in precancerous conditions, which may provide
      hints for improving epigenetic therapy and immunotherapy of cancer.

PMID- 22970313
TI  - Quantifying antimicrobial resistance at veal calf farms.
AB  - This study was performed to determine a sampling strategy to quantify the
      prevalence of antimicrobial resistance on veal calf farms, based on the variation
      in antimicrobial resistance within and between calves on five farms. Faecal
      samples from 50 healthy calves (10 calves/farm) were collected. From each
      individual sample and one pooled faecal sample per farm, 90 selected Escherichia
      coli isolates were tested for their resistance against 25 mg/L amoxicillin, 25
      mg/L tetracycline, 0.5 mg/L cefotaxime, 0.125 mg/L ciprofloxacin and 8/152 mg/L
      trimethoprim/sulfamethoxazole (tmp/s) by replica plating. From each faecal sample
      another 10 selected E. coli isolates were tested for their resistance by broth
      microdilution as a reference. Logistic regression analysis was performed to
      compare the odds of testing an isolate resistant between both test methods
      (replica plating vs. broth microdilution) and to evaluate the effect of pooling
      faecal samples. Bootstrap analysis was used to investigate the precision of the
      estimated prevalence of resistance to each antimicrobial obtained by several
      simulated sampling strategies. Replica plating showed similar odds of E. coli
      isolates tested resistant compared to broth microdilution, except for
      ciprofloxacin (OR 0.29, p <= 0.05). Pooled samples showed in general lower odds
      of an isolate being resistant compared to individual samples, although these
      differences were not significant. Bootstrap analysis showed that within each
      antimicrobial the various compositions of a pooled sample provided consistent
      estimates for the mean proportion of resistant isolates. Sampling strategies
      should be based on the variation in resistance among isolates within faecal
      samples and between faecal samples, which may vary by antimicrobial. In our
      study, the optimal sampling strategy from the perspective of precision of the
      estimated levels of resistance and practicality consists of a pooled faecal
      sample from 20 individual animals, of which 90 isolates are tested for their
      susceptibility by replica plating.

PMID- 22970312
TI  - Intercellular adhesion molecule 1 promotes HIV-1 attachment but not fusion to
      target cells.
AB  - Incorporation of intercellular adhesion molecule 1 (ICAM-1) into HIV-1 particles
      is known to markedly enhance the virus binding and infection of cells expressing
      lymphocyte function-associated antigen-1 (LFA-1). At the same time, ICAM-1 has
      been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid
      cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1
      entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted
      HIV-1 attachment to cells in a temperature-dependent manner. It exerted a
      marginal effect on virus binding in the cold, but enhanced binding up to 4-fold
      at physiological temperature. ICAM-1-independent attachment in the cold was
      readily reversible upon subsequent incubation at elevated temperature, whereas
      ICAM-1-bearing particles were largely retained by cells. The better virus
      retention resulted in a proportional increase in HIV-1 internalization and
      fusion, suggesting that ICAM-1 did not specifically accelerate endocytosis or
      fusion steps. We also measured the rates of CD4 engagement, productive
      endocytosis and HIV-endosome fusion using specific fusion inhibitors. These rates
      were virtually independent of the presence of ICAM-1 in viral particles.
      Importantly, irrespective of the presence of ICAM-1, HIV-1 escaped from the low
      temperature block, which stopped virus endocytosis and fusion, much later than
      from a membrane-impermeant fusion inhibitor targeting surface-accessible
      particles. This result, along with the complete inhibition of HIV-1 fusion by a
      small molecule dynamin inhibitor, implies this virus enters lymphoid cells used
      in this study via endocytosis and that this pathway is not altered by the viral
      ICAM-1. Our data highlight the role of ICAM-1 in stabilizing the HIV-1 attachment
      to LFA-1 expressing cells, which leads to a proportional enhancement of the
      receptor-mediated uptake and fusion with endosomes.

PMID- 22970314
TI  - Surviving chytridiomycosis: differential anti-Batrachochytrium dendrobatidis
      activity in bacterial isolates from three lowland species of Atelopus.
AB  - In the Neotropics, almost every species of the stream-dwelling harlequin toads
      (genus Atelopus) have experienced catastrophic declines. The persistence of
      lowland species of Atelopus could be explained by the lower growth rate of
      Batrachochytrium dendrobatidis (Bd) at temperatures above 25  degrees C. We
      tested the complementary hypothesis that the toads' skin bacterial microbiota
      acts as a protective barrier against the pathogen, perhaps delaying or impeding
      the symptomatic phase of chytridiomycosis. We isolated 148 cultivable bacterial
      strains from three lowland Atelopus species and quantified the anti-Bd activity
      through antagonism assays. Twenty-six percent (38 strains representing 12
      species) of the bacteria inhibited Bd growth and just two of them were shared
      among the toad species sampled in different localities. Interestingly, the
      strongest anti-Bd activity was measured in bacteria isolated from A. elegans, the
      only species that tested positive for the pathogen. The cutaneous bacterial
      microbiota is thus likely a fitness-enhancing trait that may (adaptation) or not
      (exaptation) have appeared because of natural selection mediated by
      chytridiomycosis. Our findings reveal bacterial strains for development of local
      probiotic treatments against chytridiomycosis and also shed light on the
      mechanisms behind the frog-bacteria-pathogen interaction.

PMID- 22970315
TI  - Differential requirements in endocytic trafficking for penetration of dengue
      virus.
AB  - The entry of DENV into the host cell appears to be a very complex process which
      has been started to be studied in detail. In this report, the route of functional
      intracellular trafficking after endocytic uptake of dengue virus serotype 1 (DENV
      1) strain HW, DENV-2 strain NGC and DENV-2 strain 16681 into Vero cells was
      studied by using a susceptibility to ammonium chloride assay, dominant negative
      mutants of several members of the family of cellular Rab GTPases that participate
      in regulation of transport through endosome vesicles and immunofluorescence
      colocalization. Together, the results presented demonstrate that in spite of the
      different internalization route among viral serotypes in Vero cells and
      regardless of the viral strain, DENV particles are first transported to early
      endosomes in a Rab5-dependent manner. Then a Rab7-dependent pathway guides DENV-2
      16681 to late endosomes, whereas a yet unknown sorting event controls the
      transport of DENV-2 NGC, and most probably DENV-1 HW, to the perinuclear
      recycling compartments where fusion membrane would take place releasing
      nucleocapsid into the cytoplasm. Besides the demonstration of a different
      intracellular trafficking for two DENV-2 strains that shared the initial clathrin
      independent internalization route, these studies proved for the first time the
      involvement of the slow recycling pathway for DENV-2 productive infection.

PMID- 22970316
TI  - Predator cue and prey density interactively influence indirect effects on basal
      resources in intertidal oyster reefs.
AB  - Predators can influence prey abundance and traits by direct consumption, as well
      as by non-consumptive effects of visual, olfactory, or tactile cues. The strength
      of these non-consumptive effects (NCEs) can be influenced by a variety of
      factors, including predator foraging mode, temporal variation in predator cues,
      and the density of competing prey. Testing the relative importance of these
      factors for determining NCEs is critical to our understanding of predator-prey
      interactions in a variety of settings. We addressed this knowledge gap by
      conducting two mesocosm experiments in a tri-trophic intertidal oyster reef food
      web. More specifically, we tested how a predatory fish (hardhead catfish,
      Ariopsis felis) directly influenced their prey (mud crabs, Panopeus spp.) and
      indirectly affected basal resources (juvenile oysters, Crassostrea virginica), as
      well as whether these direct and indirect effects changed across a density
      gradient of competing prey. Per capita crab foraging rates were inversely
      influenced by crab density, but they were not affected by water-borne predator
      cues. As a result, direct consumptive effects on prey foraging rates were
      stronger than non-consumptive effects. In contrast, predator cue and crab density
      interactively influenced indirect predator effects on oyster mortality in two
      experiments, with trait-mediated and density-mediated effects of similar
      magnitude operating to enhance oyster abundance. Consistent differences between a
      variable predator cue environment and other predator cue treatments (no cue and
      constant cue) suggests that an understanding of the natural risk environment
      experienced by prey is critical to testing and interpreting trait-mediated
      indirect interactions. Further, the prey response to the risk environment may be
      highly dependent on prey density, particularly in prey populations with strong
      intra-specific interactions.

PMID- 22970317
TI  - Oviposition-stimulant and ovicidal activities of Moringa oleifera lectin on Aedes
      aegypti.
AB  - BACKGROUND: Natural insecticides against the vector mosquito Aedes aegypti have
      been the object of research due to their high level of eco-safety. The water
      soluble Moringa oleifera lectin (WSMoL) is a larvicidal agent against A. aegypti.
      This work reports the effects of WSMoL on oviposition and egg hatching of A.
      aegypti. METHODOLOGY/PRINCIPAL FINDINGS: WSMoL crude preparations (seed extract
      and 0-60 protein fraction), at 0.1 mg/mL protein concentration, did not affect
      oviposition, while A. aegypti gravid females laid their eggs preferentially (73%)
      in vessels containing isolated WSMoL (0.1 mg/mL), compared with vessels
      containing only distilled water (control). Volatile compounds were not detected
      in WSMoL preparation. The hatchability of fresh eggs deposited in the solutions
      in the oviposition assay was evaluated. The numbers of hatched larvae in seed
      extract, 0-60 protein fraction and WSMoL were 45 +/- 8.7 %, 20 +/- 11 % and 55 +/
      7.5 %, respectively, significantly (p<0.05) lower than in controls containing
      only distilled water (75-95%). Embryos were visualized inside fresh control eggs,
      but not within eggs that were laid and maintained in WSMoL solution. Ovicidal
      activity was also assessed using stored A. aegypti eggs. The protein
      concentrations able to reduce the hatching rate by 50% (EC50) were 0.32, 0.16 and
      0.1 mg/mL for seed extract, 0-60 protein fraction and WSMoL, respectively. The
      absence of hatching of stored eggs treated with WSMoL at 0.3 mg/mL (EC99) after
      transfer to medium without lectin indicates that embryos within the eggs were
      killed by WSMoL. The reduction in hatching rate of A. aegypti was not linked to
      decrease in bacteria population. CONCLUSIONS/SIGNIFICANCE: WSMoL acted both as a
      chemical stimulant cue for ovipositing females and ovicidal agent at a given
      concentration. The oviposition-stimulant and ovicidal activities, combined with
      the previously reported larvicidal activity, make WSMoL a very interesting
      candidate in integrated A. aegypti control.

PMID- 22970318
TI  - Amplified Mycobacterium tuberculosis direct test for diagnosing tuberculous
      pleurisy--a diagnostic accuracy study.
AB  - BACKGROUND: The study was designed to investigate the clinical usefulness of
      Amplified Mycobacterium Tuberculosis Direct (AMTD) tests for diagnosing TB
      pleurisy. METHODS: One hundred and fifty-two patients for whom the exclusion of
      tuberculous pleural effusion was necessary were retrospectively analyzed.
      RESULTS: The sensitivity of AMTD in diagnosing pleural TB was 36.4% (20 of 55).
      Combining sputum and pleural effusion AFB smear, pleural biopsy, and AMTD test of
      pleural effusion increased sensitivity to 82.5% (33/40). There were significantly
      higher percentages of neutrophils in the pleural effusion in the positive than in
      the negative AMTD group (38.0 +/- 6.7% vs. 11.1 +/- 3.7%, p<0.001). Patients with
      symptom duration <18 days prior to pleural effusion studies had more positive
      AMTD tests than those with symptom >18 days (70% vs. 31.4%; OR 5.09; 95% CI 1.54
      16.79; p = 0.011). CONCLUSIONS: Combining AMTD tests with conventional diagnostic
      methods offer good sensitivity for pleural TB diagnosis. Patients in the early
      course of the disease are better candidates for AMTD tests.

PMID- 22970319
TI  - Crystal structure of Der f 7, a dust mite allergen from Dermatophagoides farinae.
AB  - BACKGROUND: Der f 7 is the group 7 allergen from the dust mite Dermatophagoides
      farinae, homologous to the major allergen Der p 7 from D. pteronyssinus.
      Monoclonal antibody that bind to residues Leu48 and Phe50 was found to inhibit
      IgE binding to residue Asp159, which is important for the cross-reactivity
      between Der f 7 and Der p 7. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the
      crystal structure of Der f 7 that shows an elongated and curved molecule
      consisting of two anti-parallel beta-sheets--one 4-stranded and the other 5
      stranded--that wrap around a long C-terminal helix. The overall fold of Der f 7
      is similar to Der p 7 but key difference was found in the beta1-beta2 loop
      region. In Der f 7, Leu48 and Phe50 are in close proximity to Asp159, explaining
      why monoclonal antibody binding to Leu48 and Phe50 can inhibit IgE binding to
      Asp159. Both Der f 7 and Der p 7 bind weakly to polymyxin B via a similar binding
      site that is formed by the N-terminal helix, the 4-stranded beta-sheet and the C
      terminal helix. The thermal stability of Der f 7 is significantly lower than that
      of Der p 7, and the stabilities of both allergens are highly depend on pH.
      CONCLUSION/SIGNIFICANCE: Der f 7 is homologous to Der p 7 in terms of the amino
      acid sequence and overall 3D structure but with significant differences in the
      region proximal to the IgE epitope and in thermal stability. The crystal
      structure of Der f 7 provides a basis for studying the function and allergenicity
      of this group of allergens.

PMID- 22970320
TI  - Cognitive function in childhood and lifetime cognitive change in relation to
      mental wellbeing in four cohorts of older people.
AB  - BACKGROUND: Poorer cognitive ability in youth is a risk factor for later mental
      health problems but it is largely unknown whether cognitive ability, in youth or
      in later life, is predictive of mental wellbeing. The purpose of this study was
      to investigate whether cognitive ability at age 11 years, cognitive ability in
      later life, or lifetime cognitive change are associated with mental wellbeing in
      older people. METHODS: We used data on 8191 men and women aged 50 to 87 years
      from four cohorts in the HALCyon collaborative research programme into healthy
      ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the
      National Child Development Survey, and the MRC National Survey for Health and
      Development. We used linear regression to examine associations between cognitive
      ability at age 11, cognitive ability in later life, and lifetime change in
      cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale
      and meta-analysis to obtain an overall estimate of the effect of each. RESULTS:
      People whose cognitive ability at age 11 was a standard deviation above the mean
      scored 0.53 points higher on the mental wellbeing scale (95% confidence interval
      0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89
      points (0.72, 1.07). A standard deviation improvement in cognitive ability in
      later life relative to childhood ability was associated with 0.66 points (0.39,
      0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a
      standard deviation in mental wellbeing score. Adjustment for potential
      confounding and mediating variables, primarily the personality trait neuroticism,
      substantially attenuated these associations. CONCLUSION: Associations between
      cognitive ability in childhood or lifetime cognitive change and mental wellbeing
      in older people are slight and may be confounded by personality trait
      differences.

PMID- 22970321
TI  - The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41
      is critical for viral fusion and entry.
AB  - During the process of HIV-1 fusion with the target cell, the N-terminal heptad
      repeat (NHR) of gp41 interacts with the C-terminal heptad repeat (CHR) to form
      fusogenic six-helix bundle (6-HB) core. We previously identified a crucial
      residue for 6-HB formation and virus entry--Lys63 (K63) in the C-terminal region
      of NHR (aa 54-70), which forms a hydrophobic cavity. It can form an important
      salt bridge with Asp121 (D121) in gp41 CHR. Here, we found another important
      conserved residue for virus fusion and entry, Arg46 (R46), in the N-terminal
      region of NHR (aa 35-53), which forms a hydrogen bond with a polar residue, Asn43
      (N43), in NHR, as a part of the hydrogen-bond network. R46 can also form a salt
      bridge with a negatively charged residue, Glu137 (E137), in gp41 CHR.
      Substitution of R46 with the hydrophobic residue Ala (R46A) or the negatively
      charged residue Glu (R46E) resulted in disruption of the hydrogen bond network,
      breakage of the salt bridge and reduction of 6-HB's stability, leading to
      impairment of viral fusion and decreased inhibition of N36, an NHR peptide.
      Similarly, CHR peptide C34 with substitution of E137 for Ala (E137A) or Arg
      (E137R) also exhibited reduced inhibitory activity against HIV-1 infection and
      HIV-1-mediated cell-to-cell fusion. These results suggest that the positively
      charged residue R46 and its hydrogen bond network, together with the salt bridge
      between R46 and E137, are important for viral fusion and entry and may therefore
      serve as a target for designing novel HIV fusion/entry inhibitors.

PMID- 22970322
TI  - Effectiveness of school-based education on HIV/AIDS knowledge, attitude, and
      behavior among secondary school students in Wuhan, China.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and acquired immune deficiency
      syndrome (AIDS) are among the most complex health problems in the world. Young
      people are at high risk of HIV and AIDS infections and are, therefore, in need of
      targeted prevention. School-based HIV/AIDS health education may be an effective
      way to prevent the spread of AIDS among adolescents. METHODS: The study was a
      school-based intervention conducted in three middle schools and two high schools
      in Wuhan, China, which included 702 boys and 766 girls, with ages from 11 to 18
      years old. The intervention was a one-class education program about HIV/AIDS for
      participants. HIV/AIDS knowledge, attitude, and high-risk behaviors were
      investigated using an anonymous self-administered questionnaire before and after
      the education intervention. Chi-square test was used to compare differences
      before and after the intervention. Non-conditional logistic regression analysis
      was used to identify the factors that affect HIV/AIDS knowledge. RESULTS:
      Misconceptions about basic medical knowledge and non-transmission modes of
      HIV/AIDS among all the students prevail. Approximately 10% to 40% of students had
      negative attitudes about HIV/AIDS before the intervention. After the
      intervention, all of the students had significant improvements in knowledge and
      attitude about HIV/AIDS (P<.05), indicating that educational intervention
      increased the students' knowledge significantly and changed their attitudes
      positively. Logistic regression analyses indicated that before the intervention
      the students' level of knowledge about HIV/AIDS was significantly associated with
      grade, economic status of the family, and attitudes toward participation in
      HIV/AIDS health information campaigns. CONCLUSIONS: HIV/AIDS education programs
      were welcomed by secondary students and positively influenced HIV/AIDS-related
      knowledge and attitudes. A systematic and long-term intervention among secondary
      school students must be conducted for the prevention of HIV.

PMID- 22970323
TI  - The relationship between sympatric defended species depends upon predators'
      discriminatory behaviour.
AB  - Toxic prey species living in the same environment have long been thought to
      mutually benefit from having the same warning signal by sharing the education of
      naive predators. In contrast, 'saturation theory' predicts that predators are
      physiologically limited by the amount of toxin that they can eat in a given time
      period. Therefore, sympatric species that contain the same toxin should mutually
      benefit from reduced predation even when they are visually distinct, reducing the
      benefits to visual mimicry. For the first time, we found that mutualism can occur
      between unequally defended prey that are visually distinct, although the benefits
      to each prey type depends on the predators' abilities and/or motivation to
      visually discriminate between them. Furthermore, we found that this variability
      in predatory behaviour had a significant impact on the benefits of mimicry for
      unequally defended prey. Our results demonstrate that variability in the foraging
      decisions of predators can have a significant effect on the benefits of shared
      toxicity and visual mimicry between sympatric species, and highlights the need to
      consider how predators exert selection pressures on models and mimics over their
      entire lifetimes.

PMID- 22970325
TI  - Niche variability and its consequences for species distribution modeling.
AB  - When species distribution models (SDMs) are used to predict how a species will
      respond to environmental change, an important assumption is that the
      environmental niche of the species is conserved over evolutionary time-scales.
      Empirical studies conducted at ecological time-scales, however, demonstrate that
      the niche of some species can vary in response to environmental change. We use
      habitat and locality data of five species of stream fishes collected across
      seasons to examine the effects of niche variability on the accuracy of
      projections from Maxent, a popular SDM. We then compare these predictions to
      those from an alternate method of creating SDM projections in which a
      transformation of the environmental data to similar scales is applied. The niche
      of each species varied to some degree in response to seasonal variation in
      environmental variables, with most species shifting habitat use in response to
      changes in canopy cover or flow rate. SDMs constructed from the original
      environmental data accurately predicted the occurrences of one species across all
      seasons and a subset of seasons for two other species. A similar result was found
      for SDMs constructed from the transformed environmental data. However, the
      transformed SDMs produced better models in ten of the 14 total SDMs, as judged by
      ratios of mean probability values at known presences to mean probability values
      at all other locations. Niche variability should be an important consideration
      when using SDMs to predict future distributions of species because of its
      prevalence among natural populations. The framework we present here may
      potentially improve these predictions by accounting for such variability.

PMID- 22970324
TI  - Examining the effect of household wealth and migration status on safe delivery
      care in urban India, 1992-2006.
AB  - BACKGROUND: Although the urban health issue has been of long-standing interest to
      public health researchers, majority of the studies have looked upon the urban
      poor and migrants as distinct subgroups. Another concern is, whether being poor
      and at the same time migrant leads to a double disadvantage in the utilization of
      maternal health services? This study aims to examine the trends and factors that
      affect safe delivery care utilization among the migrants and the poor in urban
      India. METHODOLOGY/PRINCIPAL FINDINGS: Using data from the National Family Health
      Survey, 1992-93 and 2005-06, this study grouped the household wealth and
      migration status into four distinct categories poor-migrant, poor-non migrant,
      non poor-migrant, non poor-non migrant. Both chi-square test and binary logistic
      regression were performed to examine the influence of household wealth and
      migration status on safe delivery care utilization among women who had
      experienced a birth in the four years preceding the survey. Results suggest a
      decline in safe delivery care among poor-migrant women during 1992-2006. The
      present study identifies two distinct groups in terms of safe delivery care
      utilization in urban India--one for poor-migrant and one for non poor-non
      migrants. While poor-migrant women were most vulnerable, non poor-non migrant
      women were the highest users of safe delivery care. CONCLUSION: This study
      reiterates the inequality that underlies the utilization of maternal healthcare
      services not only by the urban poor but also by poor-migrant women, who deserve
      special attention. The ongoing programmatic efforts under the National Urban
      Health Mission should start focusing on the poorest of the poor groups such as
      poor-migrant women. Importantly, there should be continuous evaluation to examine
      the progress among target groups within urban areas.

PMID- 22970326
TI  - Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of
      human prostate cancer cell migration.
AB  - D, L-Sulforaphane (SFN), a synthetic racemic analog of broccoli constituent L
      sulforaphane, is a highly promising cancer chemopreventive agent with in vivo
      efficacy against chemically-induced as well as oncogene-driven cancer in
      preclinical rodent models. Cancer chemopreventive effect of SFN is characterized
      by G(2)/M phase cell cycle arrest, apoptosis induction, and inhibition of cell
      migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling
      pathways often hyperactive in human cancers, including nuclear factor-kappaB,
      Akt, signal transducer and activator of transcription 3, and androgen receptor.
      The present study was designed to determine the role of Notch signaling, which is
      constitutively active in many human cancers, in anticancer effects of SFN using
      prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3,
      LNCaP, and/or LNCaP-C4-2B) to SFN as well as its naturally-occurring thio-,
      sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation) of Notch1,
      Notch2, and Notch4, which was accompanied by a decrease in levels of full-length
      Notch forms especially at the 16- and 24-hour time points. The SFN-mediated
      cleavage of Notch isoforms was associated with its transcriptional activation as
      evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration
      of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1
      and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and
      LNCaP cell migration was only marginally affected by knockdown of Notch1 and
      Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse
      Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved
      Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well
      differentiated carcinoma or poorly-differentiated prostate cancer lesions. These
      results indicate that Notch activation is largely dispensable for SFN-mediated
      inhibition of cell migration, which should be viewed as a therapeutic advantage
      as Notch activation is frequent in human prostate cancers.

PMID- 22970327
TI  - Development of multiplexed bead-based immunoassays for the detection of early
      stage ovarian cancer using a combination of serum biomarkers.
AB  - CA125 as a biomarker of ovarian cancer is ineffective for the general population.
      The aim of this study was to evaluate multiplexed bead-based immunoassay of
      multiple ovarian cancer-associated biomarkers such as transthyretin and
      apolipoprotein A1, together with CA125, to improve the identification and
      evaluation of prognosis of ovarian cancer. We measured the serum levels of CA125,
      transthyretin, and apolipoprotein A1 from the serum of 61 healthy individuals, 84
      patients with benign ovarian disease, and 118 patients with ovarian cancer using
      a multiplex liquid assay system, Luminex 100. The results were then analyzed
      according to healthy and/or benign versus ovarian cancer subjects. When CA125 was
      combined with the other biomarkers, the overall sensitivity and specificity were
      significantly improved in the ROC curve, which showed 95% and 97% sensitivity and
      specificity, respectively. At 95% specificity for all stages the sensitivity
      increased to 95.5% compared to 67% for CA125 alone. For stage I+II, the
      sensitivity increased from 30% for CA125 alone to 93.9%. For stage III+IV, the
      corresponding values were 96.5% and 91.6%, respectively. Also, the three
      biomarkers were sufficient for maximum separation between noncancer (healthy plus
      benign group) and stage I+II or all stages (I-IV) of disease. The new combination
      of transthyretin, and apolipoprotein A1 with CA125 improved both the sensitivity
      and the specificity of ovarian cancer diagnosis compared with those of individual
      biomarkers. These findings suggest the benefit of the combination of these
      markers for the diagnosis of ovarian cancer.

PMID- 22970328
TI  - Association of microRNA-499 rs3746444 polymorphism with cancer risk: evidence
      from 7188 cases and 8548 controls.
AB  - BACKGROUND: Owing to inconsistent and inconclusive results, we performed a meta
      analysis to derive a more precise estimation of the association between miR-499
      rs3746444 polymorphism and cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: A
      systematic search of the Pubmed, Excerpta Medica Database (Embase) and Chinese
      Biomedical Literature Database (CBM) databases was performed with the last search
      updated on May 6, 2012. The odds ratio (OR) and its 95% confidence interval
      (95%CI) were used to assess the strength of the association. A total of 15
      independent studies including 7,188 cases and 8,548 controls were used in the
      meta-analysis. In the present meta-analysis, we found a significant association
      between miR-499 rs3746444 polymorphism and cancer risk in the overall analysis (G
      versus A: OR = 1.10, 95%CI 1.01-1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI
      1.02-1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89-1.28, P = 0.50; GG
      versus AA: OR = 1.13, 95%CI 0.98-1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI
      1.02-1.33, P = 0.03). In the subgroup analysis by ethnicity, miR-499 rs3746444
      polymorphism was significantly associated with cancer risk in Asian population.
      In the subgroup analysis by cancer types, miR-499 rs3746444 polymorphism was
      significantly associated with breast cancer. CONCLUSIONS/SIGNIFICANCE: This meta
      analysis suggests a significant association between miR-499 rs3746444
      polymorphism and cancer risk. Large-scale and well-designed case-control studies
      are necessary to validate the risk identified in the present meta-analysis.

PMID- 22970330
TI  - Interactive multimedia to teach the life cycle of Trypanosoma cruzi, the
      causative agent of Chagas disease.

PMID- 22970329
TI  - Safety and efficacy of the 10-day melarsoprol schedule for the treatment of
      second stage Rhodesiense sleeping sickness.
AB  - OBJECTIVE: Assessment of the safety and efficacy of a 10-day melarsoprol schedule
      in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment
      on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy.
      DESIGN: Sequential conduct of a proof-of-concept trial (n = 60) and a utilization
      study (n = 78) using historic controls as comparator. SETTING: Two trial centres
      in the T.b. rhodesiense endemic regions of Tanzania and Uganda. PARTICIPANTS:
      Consenting patients with confirmed second stage disease and a minimum age of 6
      years were eligible for participation. Unconscious and pregnant patients were
      excluded. MAIN OUTCOME MEASURES: The primary outcome measures were safety and
      efficacy at end of treatment. The secondary outcome measure was efficacy during
      follow-up after 3, 6 and 12 months. RESULTS: The incidence of ES in the trial
      population was 11.2% (CI 5-17%) and 13% (CI 9-17%) in the historic data. The
      respective case fatality rates were 8.4% (CI 3-13.8%) and 9.3% (CI 6-12.6%). All
      patients discharged alive were free of parasites at end of treatment. Twelve
      months after discharge, 96% of patients were clinically cured. The mean
      hospitalization time was reduced from 29 to 13 days (p<0.0001) per patient.
      CONCLUSIONS: The 10-day melarsoprol schedule does not expose patients to a higher
      risk of ES or death than does treatment according to national schedules in
      current use. The efficacy of the 10-day melarsoprol schedule was highly
      satisfactory. No benefit could be attributed to the suramin pre-treatment. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN40537886.

PMID- 22970331
TI  - Origin and evolution of dengue virus type 3 in Brazil.
AB  - The incidence of dengue fever and dengue hemorrhagic fever in Brazil experienced
      a significant increase since the emergence of dengue virus type-3 (DENV-3) at the
      early 2000s. Despite the major public health concerns, there have been very few
      studies of the molecular epidemiology and time-scale of this DENV lineage in
      Brazil. In this study, we investigated the origin and dispersion dynamics of DENV
      3 genotype III in Brazil by examining a large number (n=107) of E gene sequences
      sampled between 2001 and 2009 from diverse Brazilian regions. These Brazilian
      sequences were combined with 457 DENV-3 genotype III E gene sequences from 29
      countries around the world. Our phylogenetic analysis reveals that there have
      been at least four introductions of the DENV-3 genotype III in Brazil, as
      signified by the presence of four phylogenetically distinct lineages. Three
      lineages (BR-I, BR-II, and BR-III) were probably imported from the Lesser
      Antilles (Caribbean), while the fourth one (BR-IV) was probably introduced from
      Colombia or Venezuela. While lineages BR-I and BR-II succeeded in getting
      established and disseminated in Brazil and other countries from the Southern
      Cone, lineages BR-III and BR-IV were only detected in one single individual each
      from the North region. The phylogeographic analysis indicates that DENV-3
      lineages BR-I and BR-II were most likely introduced into Brazil through the
      Southeast and North regions around 1999 (95% HPD: 1998-2000) and 2001 (95% HPD:
      2000-2002), respectively. These findings show that importation of DENV-3 lineages
      from the Caribbean islands into Brazil seems to be relatively frequent. Our study
      further suggests that the North and Southeast Brazilian regions were the most
      important hubs of introduction and spread of DENV-3 lineages and deserve an
      intense epidemiological surveillance.

PMID- 22970332
TI  - Dolabelladienetriol, a compound from Dictyota pfaffii algae, inhibits the
      infection by Leishmania amazonensis.
AB  - BACKGROUND: Chemotherapy for leishmaniasis, a disease caused by Leishmania
      parasites, is expensive and causes side effects. Furthermore, parasite resistance
      constitutes an increasing problem, and new drugs against this disease are needed.
      In this study, we examine the effect of the compound 8,10,18-trihydroxy-2,6
      dolabelladiene (Dolabelladienetriol), on Leishmania growth in macrophages. The
      ability of this compound to modulate macrophage function is also described.
      METHODOLOGY/PRINCIPAL FINDINGS: Leishmania-infected macrophages were treated with
      Dolabelladienetriol, and parasite growth was measured using an infectivity index.
      Nitric oxide (NO), TNF-alpha and TGF-beta production were assayed in macrophages
      using specific assays. NF-kB nuclear translocation was analyzed by western blot.
      Dolabelladienetriol inhibited Leishmania in a dose-dependent manner; the IC(50)
      was 44 uM. Dolabelladienetriol diminished NO, TNF-alpha and TGF-beta production
      in uninfected and Leishmania-infected macrophages and reduced NF-kB nuclear
      translocation. Dolabelladienetriol inhibited Leishmania infection even when the
      parasite growth was exacerbated by either IL-10 or TGF-beta. In addition,
      Dolabelladienetriol inhibited Leishmania growth in HIV-1-co-infected human
      macrophages. CONCLUSION: Our results indicate that Dolabelladienetriol
      significantly inhibits Leishmania in macrophages even in the presence of factors
      that exacerbate parasite growth, such as IL-10, TGF-beta and HIV-1 co-infection.
      Our results suggest that Dolabelladienetriol is a promising candidate for future
      studies regarding treatment of leishmaniasis, associated or not with HIV-1
      infection.

PMID- 22970333
TI  - Multiple category-lot quality assurance sampling: a new classification system
      with application to schistosomiasis control.
AB  - BACKGROUND: Originally a binary classifier, Lot Quality Assurance Sampling (LQAS)
      has proven to be a useful tool for classification of the prevalence of
      Schistosoma mansoni into multiple categories (<=10%, >10 and <50%, >=50%), and
      semi-curtailed sampling has been shown to effectively reduce the number of
      observations needed to reach a decision. To date the statistical underpinnings
      for Multiple Category-LQAS (MC-LQAS) have not received full treatment. We explore
      the analytical properties of MC-LQAS, and validate its use for the classification
      of S. mansoni prevalence in multiple settings in East Africa. METHODOLOGY: We
      outline MC-LQAS design principles and formulae for operating characteristic
      curves. In addition, we derive the average sample number for MC-LQAS when
      utilizing semi-curtailed sampling and introduce curtailed sampling in this
      setting. We also assess the performance of MC-LQAS designs with maximum sample
      sizes of n=15 and n=25 via a weighted kappa-statistic using S. mansoni data
      collected in 388 schools from four studies in East Africa. PRINCIPLE FINDINGS:
      Overall performance of MC-LQAS classification was high (kappa-statistic of 0.87).
      In three of the studies, the kappa-statistic for a design with n=15 was greater
      than 0.75. In the fourth study, where these designs performed poorly (kappa
      statistic less than 0.50), the majority of observations fell in regions where
      potential error is known to be high. Employment of semi-curtailed and curtailed
      sampling further reduced the sample size by as many as 0.5 and 3.5 observations
      per school, respectively, without increasing classification error.
      CONCLUSION/SIGNIFICANCE: This work provides the needed analytics to understand
      the properties of MC-LQAS for assessing the prevalance of S. mansoni and shows
      that in most settings a sample size of 15 children provides a reliable
      classification of schools.

PMID- 22970334
TI  - Molecular surveillance of Cryptosporidium spp., Giardia duodenalis, and
      Enterocytozoon bieneusi by genotyping and subtyping parasites in wastewater.
AB  - BACKGROUND: Despite their wide occurrence, cryptosporidiosis and giardiasis are
      considered neglected diseases by the World Health Organization. The epidemiology
      of these diseases and microsporidiosis in humans in developing countries is
      poorly understood. The high concentration of pathogens in raw sewage makes the
      characterization of the transmission of these pathogens simple through the
      genotype and subtype analysis of a small number of samples. METHODOLOGY/PRINCIPAL
      FINDINGS: The distribution of genotypes and subtypes of Cryptosporidium spp.,
      Giardia duodenalis, and Enterocytozoon bieneusi in 386 samples of combined sewer
      systems from Shanghai, Nanjing and Wuhan and the sewer system in Qingdao in China
      was determined using PCR-sequencing tools. Eimeria spp. were also genotyped to
      assess the contribution of domestic animals to Cryptosporidium spp., G.
      duodenalis, and E. bieneusi in wastewater. The high occurrence of Cryptosporidium
      spp. (56.2%), G. duodenalis (82.6%), E. bieneusi (87.6%), and Eimeria/Cyclospora
      (80.3%) made the source attribution possible. As expected, several human
      pathogenic species/genotypes, including Cryptosporidium hominis, Cryptosporidium
      meleagridis, G. duodenalis sub-assemblage A-II, and E. bieneusi genotype D, were
      the dominant parasites in wastewater. In addition to humans, the common presence
      of Cryptosporidium spp. and Eimeria spp. from rodents indicated that rodents
      might have contributed to the occurrence of E. bieneusi genotype D in samples.
      Likewise, the finding of Eimeria spp. and Cryptosporidium baileyi from birds
      indicated that C. meleagridis might be of both human and bird origins.
      CONCLUSIONS/SIGNIFICANCE: The distribution of Cryptosporidium species, G.
      duodenalis genotypes and subtypes, and E. bieneusi genotypes in urban wastewater
      indicates that anthroponotic transmission appeared to be important in
      epidemiology of cryptosporidiosis, giardiasis, and microsporidiosis in the study
      areas. The finding of different distributions of subtypes between Shanghai and
      Wuhan was indicative of possible differences in the source of C. hominis among
      different areas in China.

PMID- 22970335
TI  - Whole genome sequencing of field isolates provides robust characterization of
      genetic diversity in Plasmodium vivax.
AB  - BACKGROUND: An estimated 2.85 billion people live at risk of Plasmodium vivax
      transmission. In endemic countries vivax malaria causes significant morbidity and
      its mortality is becoming more widely appreciated, drug-resistant strains are
      increasing in prevalence, and an increasing number of reports indicate that P.
      vivax is capable of breaking through the Duffy-negative barrier long considered
      to confer resistance to blood stage infection. Absence of robust in vitro
      propagation limits our understanding of fundamental aspects of the parasite's
      biology, including the determinants of its dormant hypnozoite phase, its
      virulence and drug susceptibility, and the molecular mechanisms underlying red
      blood cell invasion. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report results from
      whole genome sequencing of five P. vivax isolates obtained from Malagasy and
      Cambodian patients, and of the monkey-adapted Belem strain. We obtained an
      average 70-400 X coverage of each genome, resulting in more than 93% of the Sal I
      reference sequence covered by 20 reads or more. Our study identifies more than
      80,000 SNPs distributed throughout the genome which will allow designing
      association studies and population surveys. Analysis of the genome-wide genetic
      diversity in P. vivax also reveals considerable allele sharing among isolates
      from different continents. This observation could be consistent with a high level
      of gene flow among parasite strains distributed throughout the world.
      CONCLUSIONS: Our study shows that it is feasible to perform whole genome
      sequencing of P. vivax field isolates and rigorously characterize the genetic
      diversity of this parasite. The catalogue of polymorphisms generated here will
      enable large-scale genotyping studies and contribute to a better understanding of
      P. vivax traits such as drug resistance or erythrocyte invasion, partially
      circumventing the lack of laboratory culture that has hampered vivax research for
      years.

PMID- 22970337
TI  - Apple can act as anti-aging on yeast cells.
AB  - In recent years, epidemiological and biochemical studies have shown that eating
      apples is associated with reduction of occurrence of cancer, degenerative, and
      cardiovascular diseases. This association is often attributed to the presence of
      antioxidants such as ascorbic acid (vitamin C) and polyphenols. The substances
      that hinder the presence of free radicals are also able to protect cells from
      aging. In our laboratory we used yeast, a unicellular eukaryotic organism, to
      determine in vivo efficacy of entire apples and their components, such as flesh,
      skin and polyphenolic fraction, to influence aging and oxidative stress. Our
      results indicate that all the apple components increase lifespan, with the best
      result given by the whole fruit, indicating a cooperative role of all apple
      components.

PMID- 22970336
TI  - A long neglected world malaria map: Plasmodium vivax endemicity in 2010.
AB  - BACKGROUND: Current understanding of the spatial epidemiology and geographical
      distribution of Plasmodium vivax is far less developed than that for P.
      falciparum, representing a barrier to rational strategies for control and
      elimination. Here we present the first systematic effort to map the global
      endemicity of this hitherto neglected parasite. METHODOLOGY AND FINDINGS: We
      first updated to the year 2010 our earlier estimate of the geographical limits of
      P. vivax transmission. Within areas of stable transmission, an assembly of 9,970
      geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010
      were used with a spatiotemporal Bayesian model-based geostatistical approach to
      estimate endemicity age-standardised to the 1-99 year age range (PvPR(1-99))
      within every 5*5 km resolution grid square. The model incorporated data on Duffy
      negative phenotype frequency to suppress endemicity predictions, particularly in
      Africa. Endemicity was predicted within a relatively narrow range throughout the
      endemic world, with the point estimate rarely exceeding 7% PvPR(1-99). The
      Americas contributed 22% of the global area at risk of P. vivax transmission, but
      high endemic areas were generally sparsely populated and the region contributed
      only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy
      negativity meant stable transmission was constrained to Madagascar and parts of
      the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global
      PAR with important high endemic areas coinciding with dense populations
      particularly in India and Myanmar. South East Asia contained areas of the highest
      endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR.
      CONCLUSIONS AND SIGNIFICANCE: This detailed depiction of spatially varying
      endemicity is intended to contribute to a much-needed paradigm shift towards
      geographically stratified and evidence-based planning for P. vivax control and
      elimination.

PMID- 22970338
TI  - The Role of Religiousness on Substance-Use Disorder Treatment Outcomes: A
      Comparison of Black and White Adolescents.
AB  - This study compares 41 Black and 124 White adolescents at intake and discharge
      from a residential treatment program for substance-use disorders. Study data were
      obtained as part of a larger study (N = 195) that sought to assess the
      relationship of helping behavior and addiction recovery. This post-hoc analysis
      aims to identify cultural strengths that may be associated with recovery from
      substance-use disorders among Black adolescents. Using regression analyses and
      controlling for the severity of substance use and background variables that
      distinguish racial groups, religious practices and behaviors at intake were
      examined. Specifically, Black youth and White youth were compared on treatment
      outcomes, including alcohol or drug use during treatment, drug craving, 12-Step
      work, and 12-Step helping. The burden of health and socioeconomic disparities at
      intake did not disproportionately disfavor Black adolescents. Outcomes related to
      12-Step measures were similar between Black and White youth. White adolescents
      reported higher craving scores at discharge, and Black adolescents were more
      likely to use drugs during treatment. High levels of religiousness at treatment
      intake were linked to greater 12-Step work and greater 12-Step helping at
      discharge. High levels of religiousness at intake were not related to drug use
      during treatment or to craving scores at discharge. The relationship between
      intake levels of religiousness and treatment-related outcomes did not differ by
      race.

PMID- 22970339
TI  - In-situ plasmon-driven chemical reactions revealed by high vacuum tip-enhanced
      Raman spectroscopy.
AB  - With strong surface plasmons excited at the metallic tip, tip-enhanced Raman
      spectroscopy (TERS) has both high spectroscopic sensitivity and high spatial
      resolution, and is becoming an essential tool for chemical analysis. It is a
      great challenge to combine TERS with a high vacuum system due to the poor optical
      collection efficiency. We used our innovatively designed home-built high vacuum
      TERS (HV-TERS) to investigate the plasmon-driven in-situ chemical reaction of 4
      nitrobenzenethiol dimerizing to dimercaptoazobenzene. The chemical reactions can
      be controlled by the plasmon intensity, which in turn can be controlled by the
      incident laser intensity, tunneling current and bias voltage. The temperature of
      such a chemical reaction can also be obtained by the clearly observed Stokes and
      Anti-Stokes HV-TERS peaks. Our findings offer a new way to design a highly
      efficient HV-TERS system and its applications to chemical catalysis and synthesis
      of molecules, and significantly extend the studies of chemical reactions.

PMID- 22970340
TI  - Shortcuts to adiabaticity in a time-dependent box.
AB  - A method is proposed to drive an ultrafast non-adiabatic dynamics of an ultracold
      gas trapped in a time-dependent box potential. The resulting state is free from
      spurious excitations associated with the breakdown of adiabaticity, and preserves
      the quantum correlations of the initial state up to a scaling factor. The process
      relies on the existence of an adiabatic invariant and the inversion of the
      dynamical self-similar scaling law dictated by it. Its physical implementation
      generally requires the use of an auxiliary expulsive potential. The method is
      extended to a broad family of interacting many-body systems. As illustrative
      examples we consider the ultrafast expansion of a Tonks-Girardeau gas and of Bose
      Einstein condensates in different dimensions, where the method exhibits an
      excellent robustness against different regimes of interactions and the features
      of an experimentally realizable box potential.

PMID- 22970341
TI  - beta-hairpin forms by rolling up from C-terminal: topological guidance of early
      folding dynamics.
AB  - That protein folding is a non-random, guided process has been known even prior to
      Levinthal's paradox; yet, guided searches, attendant mechanisms and their
      relation to primary sequence remain obscure. Using extensive molecular dynamics
      simulations of a beta-hairpin with key sequence features similar to those of
      >13,000 beta-hairpins in full proteins, we provide significant insights on the
      entire pre-folding dynamics at single-residue levels and describe a single,
      highly coordinated roll-up folding mechanism, with clearly identifiable stages,
      directing structural progression toward native state. Additional simulations of
      single-site mutants illustrate the role of three key residues in facilitating
      this roll-up mechanism. Given the many beta-hairpins in full proteins with
      similar residue arrangements and since beta-hairpins are believed to act as
      nucleation sites in early-stage folding dynamics of full proteins, the
      topologically guided mechanism seen here may represent one of Nature's strategies
      for reducing early-stage folding complexity.

PMID- 22970342
TI  - Regulation of VEGF expression by HIF-1alpha in the femoral head cartilage
      following ischemia osteonecrosis.
AB  - Juvenile femoral head osteonecrosis is due to disruption of blood supply which
      results in ischemic injury. Angiogenesis is an essential component for the
      healing of damaged head. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a master
      regulator of cellular response to hypoxia. Our histological studies showed
      increased vessel formation in cartilage in the ischemic group compared to the
      control group in a pig model of femoral head osteonecrosis. Microarray and RT-PCR
      indicated that VEGF expression was upregulated along with HIF-1alpha in the
      ischemic side. Immunohistochemistry assay demonstrated that HIF-1alpha and VEGF
      were upregulated in chondrocytes in ischemic femoral heads. Both HIF-1alpha and
      VEGF expression increased in primary chondrocytes under hypoxia station.
      Interestingly, an HIF-1alpha activator DFO further enhanced VEGF expression.
      Moreover, transfection of siRNA directed against HIF-1alpha led to inhibition of
      VEGF expression. Taken together, our data indicated that upregulation of VEGF
      during hypoxia in chondrocyte is mediated partially through HIF-1alpha.

PMID- 22970343
TI  - De Novo Donor-Specific HLA Antibody Development and Peripheral CD4(+)CD25(high)
      Cells in Kidney Transplant Recipients: A Place for Interaction?
AB  - The aim of this study was to determine whether the abundance of regulatory T
      cells (Tregs) (CD4(+)CD25(high)) affects the de novo development of anti-HLA
      donor-specific antibodies (DSAs) in kidney transplant recipients (KTRs). Methods.
      Unsensitized (PRA <= 10%, no DSA) adult primary KTRs who received a living (83%)
      or deceased (17%) KT in our Institution during 2004/2005 were included. DSA
      testing was performed monthly, and Tregs were quantified by flow cytometry every
      3 months, during the 1st year after KT. All patients received triple drug
      immunosuppressive therapy (CNI + MMF or AZA + PDN); 83% received anti-CD25.
      Results. 53 KTRs were included; 32% developed DSA during the 1st year after KT.
      Significantly lower 7-year graft survival was observed in those who developed
      DSA. No difference was observed in Treg numbers up to 9 months after KT, between
      DSA positive and negative. However, at 12 months after KT, DSA-negative patients
      had significantly higher numbers of Treg. Conclusions. Early development of DSA
      was not associated to variations in Treg abundance. The differences in Treg
      numbers observed at the late time point may reflect better immune acceptance of
      the graft and may be associated to long-term effects. Additional inhibitory
      mechanisms participating earlier in DSA development after KT deserve to be
      sought.

PMID- 22970344
TI  - Stem cells as a tool to improve outcomes of islet transplantation.
AB  - The publication of the promising results of the Edmonton protocol in 2000
      generated optimism for islet transplantation as a potential cure for Type 1
      Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of
      patients achieved long-term insulin independence. More recent data from other
      large trials like the Collaborative Islet Transplant Registry show incremental
      improvement with 44% of islet transplant recipients maintaining insulin
      independence at three years of follow-up. Multiple underlying issues have been
      identified that contribute to islet graft failure, and newer research has
      attempted to address these problems. Stem cells have been utilized not only as a
      functional replacement for beta cells, but also as companion or supportive cells
      to address a variety of different obstacles that prevent ideal graft viability
      and function. In this paper, we outline the manners in which stem cells have been
      applied to address barriers to the achievement of long-term insulin independence
      following islet transplantation.

PMID- 22970346
TI  - Elimination of Onchocerca volvulus Transmission in the Huehuetenango Focus of
      Guatemala.
AB  - In Latin America, onchocerciasis is targeted for elimination by 2012 through
      twice-yearly mass treatment of the eligible population with ivermectin. In
      Guatemala, two of the four historical endemic foci have demonstrated elimination
      of transmission, following World Health Organization guidelines. Using
      established guidelines ophthalmological, serological, and entomological
      evaluations were conducted in 2007-8 to determine the transmission status of
      onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus
      microfilariae in the anterior segment of the eye in 365 residents was 0% (95%
      confidence interval [CI] 0-0.8%), the prevalence of infection of O. volvulus in
      Simulium ochraceum among 8252 flies collected between November 2007 and April
      2008 was 0% (95% CI 0-0.02%), and the prevalence of antibodies to a recombinant
      O. volvulus antigen in 3118 school age children was 0% (95% CI 0-0.1%). These
      results showed transmission interruption; thus, in 2009 mass treatment was halted
      and posttreatment surveillance began. To verify for potential recrudescence an
      entomological evaluation (from December 2010 to April 2011) was conducted during
      the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum
      were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0
      0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been
      eliminated.

PMID- 22970347
TI  - Transmission of onchocerciasis in wadelai focus of northwestern Uganda has been
      interrupted and the disease eliminated.
AB  - Wadelai, an isolated focus for onchocerciasis in northwest Uganda, was selected
      for piloting an onchocerciasis elimination strategy that was ultimately the
      precursor for countrywide onchocerciasis elimination policy. The Wadelai focus
      strategy was to increase ivermectin treatments from annual to semiannual
      frequency and expand geographic area in order to include communities with nodule
      rate of less than 20%. These communities had not been covered by the previous
      policy that sought to control onchocerciasis only as a public health problem.
      From 2006 to 2010, Wadelai program successfully attained ultimate treatment goal
      (UTG), treatment coverage of >=90%, despite expanding from 19 to 34 communities
      and from 5,600 annual treatments to over 29,000 semiannual treatments.
      Evaluations in 2009 showed no microfilaria in skin snips of over 500 persons
      examined, and only 1 of 3011 children was IgG4 antibody positive to the OV16
      recombinant antigen. No Simulium vectors were found, and their disappearance
      could have sped up interruption of transmission. Although twice-per-year
      treatment had an unclear role in interruption of transmission, the experience
      demonstrated that twice-per-year treatment is feasible in the Ugandan setting.
      The monitoring data support the conclusion that onchocerciasis has been
      eliminated from the Wadelai focus of Uganda.

PMID- 22970348
TI  - Risk factors for asthma in a helminth endemic area in bahia, Brazil.
AB  - Protective factors associated with atopy or asthma in rural areas include
      socioeconomic level, overcrowding, and helminth infection. However, little
      epidemiological information was originated from schistosomiasis areas. This study
      aimed to investigate factors associated with asthma in a schistosomiasis endemic
      area. A questionnaire was used to obtain information on demographics,
      socioeconomic, and environmental features. The ISAAC questionnaire was used to
      identify individuals with asthma. Parasitological exam was done in all
      participants and skin prick test to aeroallergens in all asthmatics. Prevalence
      of Schistosoma mansoni infection was 57.4% and Ascaris lumbricoides, 30.8%.
      Asthma was found in 13.1% of the population, and 35.1% of them had a positive
      SPT. Active and passive smoking was positively associated with asthma, whereas A.
      lumbricoides was negatively associated. In a schistosomiasis hyperendemic region,
      current infection with A. lumbricoides is protective against asthma. However, we
      cannot rule out the involvement of S. mansoni infection in this process.

PMID- 22970349
TI  - En Face OCT Imaging for the Diagnosis of Outer Retinal Tubulations in Age-Related
      Macular Degeneration.
AB  - Purpose. "En face" is an emerging imaging technique derived from spectral domain
      optical coherence tomography (OCT). It produces frontal sections of retinal
      layers, also called "C-scan OCT." Outer retinal tubulations (ORTs) in age-related
      macular degeneration (AMD) are a recent finding evidenced by spectral-domain OCT.
      The aim of this study is to characterize the morphology of ORT according to the
      form of AMD, using "en-face" spectral domain OCT. Methods. "En face" OCT imaging
      was prospectively performed in 26 consecutive eyes with AMD that also had ORT.
      Results. There were 15 neovascular, 8 atrophic, and 3 eyes with a mixed (fibrotic
      and atrophic) form of AMD. Among the neovascular group, the most frequent
      tubulation pattern on "en-face" OCT was a branching network emanating from a
      fibrovascular scar; we term this pattern as "pseudodendritic." It did not require
      treatment when observed as an isolated finding. In all cases of atrophic AMD, the
      tubular network was located at the edge of the geographic atrophy area, and
      formed a "perilesional" pattern. Six atrophic cases showed tubular invaginations
      inside this area. Conclusion. "En face" OCT is a valuable technique in the
      diagnosis and followup of macular disease. It revealed the main characteristic
      patterns of ORT associated with neovascular and atrophic AMD.

PMID- 22970345
TI  - Human schistosome infection and allergic sensitisation.
AB  - Several field studies have reported an inverse relationship between the
      prevalence of helminth infections and that of allergic sensitisation/atopy.
      Recent studies show that immune responses induced by helminth parasites are, to
      an extent, comparable to allergic sensitisation. However, helminth products
      induce regulatory responses capable of inhibiting not only antiparasite immune
      responses, but also allergic sensitisation. The relative effects of this
      immunomodulation on the development of protective schistosome-specific responses
      in humans has yet to be demonstrated at population level, and the clinical
      significance of immunomodulation of allergic disease is still controversial.
      Nonetheless, similarities in immune responses against helminths and allergens
      pose interesting mechanistic and evolutionary questions. This paper examines the
      epidemiology, biology and immunology of allergic sensitisation/atopy, and
      schistosome infection in human populations.

PMID- 22970350
TI  - Parents' Readiness to Change Affects BMI Reduction Outcomes in Adolescents with
      Polycystic Ovary Syndrome.
AB  - Evidence supports the importance of parental involvement for youth's ability to
      manage weight. This study utilized the stages of change (SOC) model to assess
      readiness to change weight control behaviors as well as the predictive value of
      SOC in determining BMI outcomes in forty adolescent-parent dyads (mean adolescent
      age = 15 +/- 1.84 (13-20), BMI = 37 +/- 8.60; 70% white) participating in a
      weight management intervention for adolescent females with polycystic ovary
      syndrome (PCOS). Adolescents and parents completed a questionnaire assessing
      their SOC for the following four weight control domains: increasing dietary
      portion control, increasing fruit and vegetable consumption, decreasing dietary
      fat, and increasing usual physical activity. Linear regression analyses indicated
      that adolescent change in total SOC from baseline to treatment completion was not
      predictive of adolescent change in BMI from baseline to treatment completion.
      However, parent change in total SOC from baseline to treatment completion was
      predictive of adolescent change in BMI, (t(24) = 2.15, p = 0.043). Findings
      support future research which carefully assesses adolescent and parent SOC and
      potentially develops interventions targeting adolescent and parental readiness to
      adopt healthy lifestyle goals.

PMID- 22970351
TI  - The Neurological Complications of Nutritional Deficiency following Bariatric
      Surgery.
AB  - Neurologic complications of bariatric surgery have become increasingly recognized
      with the rising numbers of procedures and the increasing prevalence of obesity in
      the US. Deficits are most commonly seen with thiamine, vitamin B(12), folate,
      vitamin D, vitamin E, and copper deficiencies. The neurological findings observed
      with these nutritional deficiencies are variable and include encephalopathy,
      optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. We
      review the neurological complications of bariatric surgery and emphasize that
      these findings may vary based on the specific type of bariatric surgery and time
      elapsed from the procedure.

PMID- 22970352
TI  - The Changing Epidemiology of Oropharyngeal Candidiasis in Patients with HIV/AIDS
      in the Era of Antiretroviral Therapy.
AB  - The impact of antiretroviral therapy (ART) on opportunistic conditions in HIV
      patients continues to evolve. We specifically studied the changing epidemiology
      of oropharyngeal candidiasis (OPC) in 215 HIV/AIDS patients. Status of yeast
      colonization was assessed from oral rinse samples, and preliminary yeast
      identification was made using CHROMagar Candida and confirmed with standard
      microbiological techniques and/or molecular sequencing. Susceptibility to
      fluconazole was determined by CHROMagar Candida agar dilution screening and CLSI
      broth microdilution. 176 (82%) patients were colonized and 59 (27%) patients had
      symptomatic OPC. Candida albicans was the most prevalent species, though C.
      glabrata and C. dubliniensis were detected in 29% of isolates. Decreased
      fluconazole susceptibility occurred in 10% of isolates. Previous ART reduced the
      risk of OPC, while smoking increased the risk of colonization. Oral yeast
      colonization and symptomatic infection remain common even with advances in HIV
      therapy. C. albicans is the most common species, but other yeasts are prevalent
      and may have decreased susceptibility to fluconazole.

PMID- 22970353
TI  - Thirty years later: pregnancies in females perinatally infected with human
      immunodeficiency virus-1.
AB  - The first cases of mother to child transmission of human immunodeficiency virus
      (HIV) were described more than two decades ago and since then several thousands
      more have been reported in western countries. In the early 1980s the majority of
      perinatally acquired HIV children did not survive beyond childhood. However
      combined antiretroviral therapy (ART) for perinatally HIV-acquired children has
      prolonged their survival and in the past 2 decades, many have reached adulthood.
      As the perinatally HIV-infected females become sexually active, they are in turn
      at risk for pregnancy and of transmitting HIV infection to their children. A
      considerable proportion of this population appears to engage in unprotected
      sexual intercourse leading to teenage pregnancies, STDs, and abnormal cervical
      cytology despite frequent contact with HIV health care providers and clinics.
      Currently there is a paucity of data regarding pregnancy and neonatal outcomes in
      HIV perinatally infected women. As increasing number of pregnancies will occur
      among this population we must continue to monitor and focus on their reproductive
      health issues to improve perinatal and long-term maternal outcomes. This paper
      will summarize our current knowledge about reproductive health issues and
      identify areas for future inquiry.

PMID- 22970354
TI  - A Comparison of Chronic Periodontitis in HIV-Seropositive Subjects and the
      General Population in the Ga-Rankuwa Area, South Africa.
AB  - The effect of HIV infection on the prevalence and the rate of progression of
      chronic periodontitis is not clear. The aim of this study was to compare
      parameters associated with the severity of chronic periodontitis in terms of
      periodontal probing depths, gingival recession, plaque indexes, and bleeding
      indexes of HIV-seropositive subjects and healthy age-matched control subjects,
      and of HIV-seropositive subjects on highly active antiretroviral therapy and
      those not receiving such treatment. Two cohorts of subjects with chronic
      periodontitis were recruited for this study over a period of six months. There
      were 30 HIV-seropositive subjects, and 30 control subjects. Periodontal probing
      depths, gingival marginal recession, plaque indexes, and bleeding indexes were
      compared by HIV serostatus, the use of highly active antiretroviral therapy, and
      CD4+ T-cell counts. All participants were black persons between the age of 18 and
      45 and were of a similar socioeconomic status and age. The results of this study
      indicate that chronic periodontitis in HIV-seropositive subjects is similar in
      terms of mean periodontal probing depth, gingival marginal recession, plaque
      index, and bleeding index to that in healthy age-matched control subjects, and a
      low CD4+ T-cell count does not appear to be a risk factor for increased severity
      of chronic periodontitis.

PMID- 22970355
TI  - The effects of unripe grape juice on lipid profile improvement.
AB  - Introduction. Consumption of unripe grape juice (verjuice) has been portrayed by
      the traditional belief, as a means of combating dyslipidemia. We aimed to
      evaluate the effects of unripe grape juice consumption on lipid profile in
      healthy human volunteers. Methods. We asked 42 enrolled volunteers to drink 10 cc
      of verjuice within 30 minutes to 2 hours after lunch and 10 cc of it after
      dinner. After taking 120 doses of verjuice, another fasting lipid profile was
      obtained from each participant. The statistical analysis was performed by SPSS 13
      software. Results. After analysis of the data, the mean +/- standard deviation
      for all the variables was obtained. Among those improvement of HDL-C was
      significant after the trial (P value < 0.001). TG, TC, and LDL improvement were
      not significant. Conclusion. Our study declared that verjuice has a dramatic
      effect on improving HDL-C level of serum but no any other lipid improvement
      effect was obtained.

PMID- 22970357
TI  - Depression Treatment Patterns among Elderly with Cancer.
AB  - Little is known about cancer treatment patterns among the elderly as depression
      and cancer in this older population have not been well explored. This study seeks
      to fill a gap in the literature by using data from the Medicare Current
      Beneficiary Survey from years 2000-2005 to examine depression treatment patterns
      among elderly diagnosed with both cancer and depression. Depression treatments
      examined include antidepressants with and without psychotherapy. We found that of
      those with both cancer and depression, 57.7% reported antidepressant use only,
      19.7% received psychotherapy with or without antidepressants, and 22.6% had no
      depression treatment. We found those with greater comorbidity, of a minority
      race, with lower levels of education, and living in rural areas were less likely
      to receive treatment for depression. These findings highlight the need to address
      disparities in the treatment of depression in the elderly population with cancer.

PMID- 22970359
TI  - Perceptions of pediatric nurse practitioners and how a pulmonary function
      printout influenced practice.
AB  - The rate of asthma in the pediatric population has risen over the last two
      decades and is now considered to be the most common serious chronic disease in
      children and adolescents as well as a serious public health concern. In one
      suburban, Pennsylvania nurse-managed clinic, a group of pediatric nurse
      practitioners (PNPs), noted an increase in the number of children with asthma and
      purchased a pulmonary function machine (Spirometer). The purpose of this paper is
      to discuss how the integration of a pulmonary function measurement printout
      influenced a small group of PNPs visit satisfaction, their delivery of nursing
      care, and the response of the families. As the incidence of asthma increases in
      the pediatric population, nurse practitioners and other healthcare professionals
      can take a leading role in patient teaching and provision of care by augmenting
      their practice with new technology combined with continued education for the
      client and family.

PMID- 22970358
TI  - Surgery should complement endocrine therapy for elderly postmenopausal women with
      hormone receptor-positive early-stage breast cancer.
AB  - Introduction. Endocrine therapy (ET) is an integral part of breast cancer (BC)
      treatment with surgical resection remaining the cornerstone of curative
      treatment. The objective of this study is to compare the survival of elderly
      postmenopausal women with hormone receptor-positive early-stage BC treated with
      ET alone, without radiation or chemotherapy, versus ET plus surgery. Materials
      and Methods. This is a retrospective study based on a prospective database. The
      medical records of postmenopausal BC patients referred to the surgical oncology
      service of two hospitals during an 8-year period were reviewed. All patients were
      to receive ET for a minimum of four months before undergoing any surgery.
      Results. Fifty-one patients were included and divided in two groups, ET alone and
      ET plus surgery. At last follow-up in exclusive ET patients (n = 28), 39% had
      stable disease or complete response, 22% had progressive disease, of which 18%
      died of breast cancer, and 39% died of other causes. In surgical patients (n =
      23), 78% were disease-free, 9% died of recurrent breast cancer, and 13% died of
      other causes. Conclusions. These results suggest that surgical resection is
      beneficial in this group and should be considered, even for patients previously
      deemed ineligible for surgery.

PMID- 22970356
TI  - Monitoring in the intensive care.
AB  - In critical care, the monitoring is essential to the daily care of ICU patients,
      as the optimization of patient's hemodynamic, ventilation, temperature,
      nutrition, and metabolism is the key to improve patients' survival. Indeed, the
      decisive endpoint is the supply of oxygen to tissues according to their metabolic
      needs in order to fuel mitochondrial respiration and, therefore, life. In this
      sense, both oxygenation and perfusion must be monitored in the implementation of
      any resuscitation strategy. The emerging concept has been the enhancement of
      macrocirculation through sequential optimization of heart function and then
      judging the adequacy of perfusion/oxygenation on specific parameters in a
      strategy which was aptly coined "goal directed therapy." On the other hand, the
      maintenance of normal temperature is critical and should be regularly monitored.
      Regarding respiratory monitoring of ventilated ICU patients, it includes serial
      assessment of gas exchange, of respiratory system mechanics, and of patients'
      readiness for liberation from invasive positive pressure ventilation. Also, the
      monitoring of nutritional and metabolic care should allow controlling nutrients
      delivery, adequation between energy needs and delivery, and blood glucose. The
      present paper will describe the physiological basis, interpretation of, and
      clinical use of the major endpoints of perfusion/oxygenation adequacy and of
      temperature, respiratory, nutritional, and metabolic monitorings.

PMID- 22970360
TI  - Minimally invasive spinal arthrodesis in osteoporotic population using a
      cannulated and fenestrated augmented screw: technical description and clinical
      experience.
AB  - We describe a percutaneous or minimally invasive approach to apply an
      augmentation of pedicle fenestrated screws by injection of the PMMA bone cement
      through the implant and determine the safety and efficiency of this technique in
      a clinical series of 15 elderly osteoporotic patients. Clinical outcome and the
      function were assessed using respectively the Visual Analogue Scale (VAS) score
      and the Oswestry Disability Index (ODI). Peri- and post-operative complications
      were monitored during a minimum of 2 years of follow-up. Radiographic follow-up
      was based on plain fluoroscopic control at 3, 6 and 12 months and every year. In
      this approach, four steps were considered with care: optimal positioning of the
      screws, correct alignment of the screw heads, waiting time before the injection
      of cement, fluoroscopic control of the cement injection. Using these precautions,
      only 2 minor complications occurred. VAS scores and ODI questionnaires showed a
      statistically significant improvement up to 13.3 months postoperatively. No
      radiological complications were observed. Based on this experience, PMMA
      augmentation technique through the novel fenestrated screws provided an effective
      and long lasting fixation in osteoporotic patients. Applying this procedure
      through percutaneous or minimally invasive approach under fluoroscopic control
      seems to be safe.

PMID- 22970361
TI  - Matrix metalloproteinases in neuropathic pain and migraine: friends, enemies, and
      therapeutic targets.
AB  - Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent
      endopeptidases that mediate extracellular matrix turnover and associated
      processes, such as cell survival, growth, and differentiation. This paper
      discusses important functions of MMP in the normal and injured nervous system,
      focusing on the role played by these proteases in neurological pain syndromes,
      most prominently in neuropathic pain and migraine headaches. In the past decade,
      metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9
      acting as an initiator of the neuropathic cascade. Increased MMP activity was
      detected in migraine patients, independent of aura, in tight association with
      metabolic derangements. The therapeutic implications of MMP inhibition are
      considered in the context of neurogenic pain regulation.

PMID- 22970362
TI  - Prolonged Action Potential and After depolarizations Are Not due to Changes in
      Potassium Currents in NOS3 Knockout Ventricular Myocytes.
AB  - Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3(-/-))
      exhibit prolonged action potential (AP) duration and enhanced spontaneous
      activity (early and delayed afterdepolarizations) during beta-adrenergic (beta
      AR) stimulation. Studies have shown that nitric oxide is able to regulate various
      K(+) channels. Our objective was to examine if NOS3(-/-) myocytes had altered
      K(+) currents. APs, transient outward (I(to)), sustained (I(Ksus)), and inward
      rectifier (I(K1)) K(+) currents were measured in NOS3(-/-) and wild-type (WT)
      myocytes. During beta-AR stimulation, AP duration (measured as 90% repolarization
      APD(90)) was prolonged in NOS3(-/-) compared to WT myocytes. Nevertheless, we did
      not observe differences in I(to), I(Ksus), or I(K1) between WT and NOS3(-/-)
      myocytes. Our previous work showed that NOS3(-/-) myocytes had a greater Ca(2+)
      influx via L-type Ca(2+) channels with beta-AR stimulation. Thus, we measured
      beta-AR-stimulated SR Ca(2+) load and found a greater increase in NOS3(-/-)
      versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3(-/-)
      myocytes is not due to changes in I(to), I(Ksus), or I(K1). Furthermore, the
      increase in spontaneous activity in NOS3(-/-) myocytes may be due to a greater
      increase in SR Ca(2+) load. This may have important implications for heart
      failure patients, where arrhythmias are increased and NOS3 expression is
      decreased.

PMID- 22970363
TI  - Imaging review of procedural and periprocedural complications of central venous
      lines, percutaneous intrathoracic drains, and nasogastric tubes.
AB  - Placements of central venous lines (CVC), percutaneous intrathoracic drains
      (ITDs), and nasogastric tubes (NGTs) are some of the most common interventional
      procedures performed on patients that are unconscious and in almost all intensive
      care/high dependency patients in one form or the other. These are standard
      procedures within the remit of physicians, and other trained health
      professionals. Procedural complications may occur in 7%-15% of patients depending
      upon the intervention and experience of the operator. Most complications are
      minor, but other serious complications may add significantly to morbidity and
      even mortality of already compromised patients. Imaging findings are the key to
      the detection of misplaced lines, and tubes and their prompt recognition are
      vital to avoid harm to the patient. It is, therefore, pertinent that healthcare
      professionals who perform these procedures are familiar with imaging
      complications of these procedures. Here, we present the imaging characteristics
      of procedural complications.

PMID- 22970364
TI  - Cognitive control and discourse comprehension in schizophrenia.
AB  - Cognitive deficits across a wide range of domains have been consistently observed
      in schizophrenia and are linked to poor functional outcome (Green, 1996; Carter,
      2006). Language abnormalities are among the most salient and include disorganized
      speech as well as deficits in comprehension. In this review, we aim to evaluate
      impairments of language processing in schizophrenia in relation to a domain
      general control deficit. We first provide an overview of language comprehension
      in the healthy human brain, stressing the role of cognitive control processes,
      especially during discourse comprehension. We then discuss cognitive control
      deficits in schizophrenia, before turning to evidence suggesting that
      schizophrenia patients are particularly impaired at processing meaningful
      discourse as a result of deficits in control functions. We conclude that domain
      general control mechanisms are impaired in schizophrenia and that during language
      comprehension this is most likely to result in difficulties during the processing
      of discourse-level context, which involves integrating and maintaining multiple
      levels of meaning. Finally, we predict that language comprehension in
      schizophrenia patients will be most impaired during discourse processing. We
      further suggest that discourse comprehension problems in schizophrenia might be
      mitigated when conflicting information is absent and strong relations amongst
      individual words are present in the discourse context."There is no "centre of
      Speech" in the brain any more than there is a faculty of Speech in the mind.The
      entire brain, more or less, is at work in a man who uses language"William
      JamesFrom The Principles of Psychology, 1890"The mind in dementia praecox is like
      an orchestra without a conductor"Kraepelin, 1919.

PMID- 22970365
TI  - Sex differences in facial, prosodic, and social context emotional recognition in
      early-onset schizophrenia.
AB  - The purpose of the present study was to determine sex differences in facial,
      prosodic, and social context emotional recognition in schizophrenia (SCH). Thirty
      eight patients (SCH, 20 females) and 38 healthy controls (CON, 20 females)
      participated in the study. Clinical scales (BPRS and PANSS) and an Affective
      States Scale were applied, as well as tasks to evaluate facial, prosodic, and
      within a social context emotional recognition. SCH showed lower accuracy and
      longer response times than CON, but no significant sex differences were observed
      in either facial or prosody recognition. In social context emotions, however,
      females showed higher empathy than males with respect to happiness in both
      groups. SCH reported being more identified with sad films than CON and females
      more with fear than males. The results of this study confirm the deficits of
      emotional recognition in male and female patients with schizophrenia compared to
      healthy subjects. Sex differences were detected in relation to social context
      emotions and facial and prosodic recognition depending on age.

PMID- 22970366
TI  - Integrated treatment to achieve functional recovery for first-episode psychosis.
AB  - This study describes an integrated treatment approach that was implemented to
      enhance functional recovery in first-episode psychotic patients. Patients were
      randomized to two treatment conditions: either to an integrated treatment
      approach: pharmacotherapy, psychosocial treatment, and psychoeducation
      (experimental group: N = 39) or to medication alone (control group: N = 34).
      Patients were evaluated at baseline and after one year of treatment. Functional
      recovery was assessed according to symptomatic and functional remission. At the
      end of treatment, experimental patients showed a 94.9% of symptomatic remission
      compared to 58.8% of the control group. Functional remission was 56.4% for the
      experimental group and 3.6% for the control group, while 56.4% of the
      experimental group met both symptomatic and functional remission criteria and
      were considered recovered compared to 2.9% of the control group.

PMID- 22970367
TI  - Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel
      Therapeutic Strategies to Overcome Resistance in NSCLC Patients.
AB  - The epidermal growth factor receptor (EGFR) is a well-characterized oncogene that
      is frequently activated by somatic kinase domain mutations in non-small cell lung
      cancer (NSCLC). EGFR TKIs are effective therapies for NSCLC patients whose tumors
      harbor an EGFR activating mutation. However, EGFR TKI treatment is not curative
      in patients because of both primary and secondary treatment resistance. Studies
      over the last decade have identified mechanisms that drive primary and secondary
      resistance to EGFR TKI treatment. The elucidation of mechanisms of resistance to
      EGFR TKI treatment provides a basis for the development of therapeutic strategies
      to overcome resistance and enhance outcomes in NSCLC patients. In this paper, we
      summarize the mechanisms of resistance to EGFR TKIs that have been identified to
      date and discusses potential therapeutic strategies to overcome EGFR TKI
      resistance in NSCLC patients.

PMID- 22970369
TI  - Relationships between Social Resources and Healthful Behaviors across the Age
      Spectrum.
AB  - Background. We examined cross-sectional relationships of social resources with
      health behaviors in adults ages 18-93 years. Methods. Baseline data from a 2009
      risk behavior intervention trial were used to measure social resources, physical
      activity, and fruit and vegetable intake in 2,440 adults. To evaluate
      associations overall and within 4 age groups (18-34, 35-49, 50-64, and 65-93 y),
      we used multivariable regression. Results. Mean (SD) age was 49.4 (15) years,
      physical activity was 346 (304) minutes/week, and fruit and vegetable intake was
      3.4 (2.4) servings/day. Mean social resource score was 1.2 (0-4 scale) in 18-34
      year olds, 1.1 in all other age groups (P = 0.04). In multivariable models, for
      each one-point increment in social resource score, the odds ratio for getting 150
      959 minutes of physical activity/wk (compared to <150 min/wk) was 3.7 (95% CI 3.0
      4.6). Each one-point increment in score was also associated with 29% (95% CI: 23
      35%) more servings of fruit and vegetables. We did not observe effect
      modification by age group. Conclusions. Although younger adults reported slightly
      higher resources than older adults, the magnitude of association between social
      resources and healthful behaviors did not differ between them.

PMID- 22970370
TI  - Anemia and iron deficiency in pregnancy.

PMID- 22970368
TI  - Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth:
      Effects on Nephron Number and Long-Term Renal Health.
AB  - Epidemiological studies have clearly demonstrated a strong association between
      low birth weight and long-term renal disease. A potential mediator of this long
      term risk is a reduction in nephron endowment in the low birth weight infant at
      the beginning of life. Importantly, nephrons are only formed early in life;
      during normal gestation, nephrogenesis is complete by about 32-36 weeks, with no
      new nephrons formed after this time during the lifetime of the individual. Hence,
      given that a loss of a critical number of nephrons is the hallmark of renal
      disease, an increased severity and acceleration of renal disease is likely when
      the number of nephrons is already reduced prior to disease onset. Low birth
      weight can result from intrauterine growth restriction (IUGR) or preterm birth; a
      high proportion of babies born prematurely also exhibit IUGR. In this paper, we
      describe how IUGR and preterm birth adversely impact on nephrogenesis and how a
      subsequent reduced nephron endowment at the beginning of life may lead to long
      term risk of renal disease, but not necessarily hypertension.

PMID- 22970373
TI  - Podocyturia as a diagnostic marker for preeclampsia amongst high-risk pregnant
      patients.
AB  - Urinary podocyte (podocyturia) has been studied as a diagnostic marker for
      preeclampsia. We sought to validate its use in preeclampsia and in
      differentiating it from other high risk pregnancy states. We studied an obstetric
      population at high risk to develop preeclampsia (study group) and uncomplicated
      pregnancies (control group) by analyzing their urine sediment for podocytes
      within 24 hours of delivery. Podocytes were identified by immunohistochemistry
      using the podocyte-specific protein synaptopodin. Of the 56 patients who were
      enrolled, 29 patients were diagnosed with preeclampsia, 9 patients had
      hypertensive conditions such as chronic and gestational hypertension, 6 patients
      had Type I/II and gestational diabetes mellitus, 3 patients were classified as
      others, and 9 patients exhibited uncomplicated pregnancies. Podocyturia was
      identified in 11 out of 29 (38%) of patients with preeclampsia/eclampsia, 3 out
      of 9 (33%) with gestational and chronic hypertension, and 3 out of 6 (50%) with
      Type I/II and gestational diabetes mellitus. None of the 9 patients (0%) with
      uncomplicated pregnancies demonstrated podocyturia. The sensitivity and
      specificity of podocyturia for preeclampsia were found to be 38% and 70%. Our
      study showed that podocyturia does not appear to be a sensitive nor a specific
      marker to diagnose preeclampsia.

PMID- 22970371
TI  - Glucocorticoids and preterm hypoxic-ischemic brain injury: the good and the bad.
AB  - Fetuses at risk of premature delivery are now routinely exposed to maternal
      treatment with synthetic glucocorticoids. In randomized clinical trials, these
      substantially reduce acute neonatal systemic morbidity, and mortality, after
      premature birth and reduce intraventricular hemorrhage. However, the overall
      neurodevelopmental impact is surprisingly unclear; worryingly, postnatal
      glucocorticoids are consistently associated with impaired brain development. We
      review the clinical and experimental evidence on how glucocorticoids may affect
      the developing brain and highlight the need for systematic research.

PMID- 22970372
TI  - Fetal programming of the neuroendocrine-immune system and metabolic disease.
AB  - Adverse uterine environments experienced during fetal development can alter the
      projected growth pattern of various organs and systems of the body, leaving the
      offspring at an increased risk of metabolic disease. The thrifty phenotype
      hypothesis has been demonstrated as an alteration to the growth trajectory to
      improve the survival and reproductive fitness of the individual. However, when
      the intrauterine environment does not match the extrauterine environment problems
      can arise. With the increase in metabolic diseases in both Westernized and
      developing countries, it is becoming apparent that there is an environmental
      disconnect with the extrauterine environment. Therefore, the focus of this paper
      will be to explore the effects of maternal malnutrition on the offspring's
      susceptibility to metabolic disorders such as obesity, cardiovascular disease,
      and diabetes with emphasis on programming of the neuroendocrine-immune system.

PMID- 22970374
TI  - Gender and Side-to-Side Differences of Femoral Condyles Morphology: Osteometric
      Data from 360 Caucasian Dried Femori.
AB  - The purpose of the present study was to conduct direct measurements in a large
      sample of dried femori in order to record certain morphometric parameters of the
      femoral condyles and determine whether there are gender and side differences.
      Three hundred sixty (Greek) Caucasian dried femori (180 left and 180 right), from
      192 males and 168 females, were measured using a digital caliper. The mean age
      was 67.52 years. The mean bicondylar width of the femur was 8.86 cm +/- 0.42 cm
      in men and 7.85 cm +/- 0.30 cm in women (P < 0.01). The relative values for the
      medial condylar depth were 6.11 cm +/- 0.34 cm and 5.59 cm +/- 0.29 cm (P <
      0.05); for the lateral condylar depth were 6.11 cm +/- 0.33 cm and 5.54 cm +/-
      0.21 cm (P < 0.01); for the intercondylar width were 2.20 cm +/- 0.18 cm and 1.87
      cm +/- 0.10 cm (P < 0.001); for the intercondylar depth were 2.78 cm +/- 0.16 cm
      and 2.37 cm +/- 0.12 cm (P < 0.001). No significant side-to-side difference was
      observed in any parameter. The femoral condyles differences in anatomy between
      genders might be useful to the design of total knee prostheses. The contralateral
      healthy side can be safely used for preoperative templating since there were no
      significant side differences.

PMID- 22970375
TI  - Characterization and quenching of autofluorescence in piglet testis tissue and
      cells.
AB  - Significant intrinsic fluorescence in tissues and in disassociated cells can
      interfere with fluorescence identification of target cells. The objectives of the
      present study were (1) to examine an intrinsic fluorescence we observed in both
      the piglet testis tissue and cells and (2) to test an effective method to block
      the autofluorescence. We observed that a number of granules within the testis
      interstitial cells were inherently fluorescent, detectable using epifluorescence
      microscopy, confocal laser scanning microscopy, and flow cytometry. The emission
      wavelength of the autofluorescent substance ranged from 425 to 700 nm, a range
      sufficiently broad that could potentially interfere with fluorescence techniques.
      When we treated the samples with Sudan Black B for different incubation times,
      the intrinsic fluorescence was completely masked after treatment for 10-15 min of
      the testis tissue sections or for 8 min of the testis cells, without compromising
      specific fluorescence labeling of gonocytes with lectin Dolichos biflorus
      agglutinin (DBA). We speculate that the lipofuscin or lipofuscin-like pigments
      within Leydig cell granules were mainly responsible for the observed intrinsic
      fluorescence in piglet testes. The method described in the present study can
      facilitate the identification and characterization of piglet gonocytes using
      fluorescence microscopy.

PMID- 22970376
TI  - Role of mean platelet volume in diagnosis of childhood acute appendicitis.
AB  - Introduction. Acute appendicitis is the leading cause of abdominal pain in
      children requiring emergency surgical intervention. The aim of this study is to
      investigate the diagnostic value of MPV in early diagnosis of acute appendicitis
      cases in pediatric age group. Methods. This study was performed retrospectively.
      Three hundred five patients operated on with the diagnosis of appendicitis and
      pathologically found to be acute appendicitis were classified as Group 1 and 305
      healthy children were classified as control Group 2. Results. One hundred ninety
      seven of 305 cases in Group 1 are males (64.6%), in Group 2, 151 of 305 cases are
      males (49.5%). The mean MPV in Group 1 was 7.9 +/- 0.9 (fL), and whereas in Group
      2 was 7.7 +/- 0.8 (fL). There was no statistically significant difference
      regarding MPV values (P > 0.05). Conclusion. In our study we detected that mean
      platelet volume has no diagnostic value in pediatric acute appendicitis cases.

PMID- 22970377
TI  - Intracellular Delivery of siRNA by Polycationic Superparamagnetic Nanoparticles.
AB  - The siRNA transfection efficiency of nanoparticles (NPs), composed of a
      superparamagnetic iron oxide core modified with polycationic polymers
      (poly(hexamethylene biguanide) or branched polyethyleneimine), were studied in
      CHO-K1 and HeLa cell lines. Both NPs demonstrated to be good siRNA transfection
      vehicles, but unmodified branched polyethyleneimine (25 kD) was superior on both
      cell lines. However, application of an external magnetic field during
      transfection (magnetofection) increased the efficiency of the superparamagnetic
      NPs. Furthermore, our results reveal that these NPs are less toxic towards CHO-K1
      cell lines than the unmodified polycationic-branched polyethyleneimine (PEI). In
      general, the external magnetic field did not alter the cell's viability nor it
      disrupted the cell membranes, except for the poly(hexamethylene biguanide)
      modified NP, where it was observed that in CHO-K1 cells application of the
      external magnetic field promoted membrane damage. This paper presents new
      polycationic superparamagnetic NPs as promising transfection vehicles for siRNA
      and demonstrates the advantages of magnetofection.

PMID- 22970378
TI  - Dietary Omega-3 Fatty Acids Do Not Change Resistance of Rat Brain or Liver
      Mitochondria to Ca(2+) and/or Prooxidants.
AB  - Omega-3 polyunsaturated fatty acids (n-3 PUFAs) block apoptotic neuronal cell
      death and are strongly neuroprotective in acute and chronic neurodegeneration.
      Theoretical considerations, indirect data, and consideration of parsimony lead to
      the hypothesis that modulation of mitochondrial pathway(s) underlies at least
      some of the neuroprotective effects of n-3 PUFAs. We therefore systematically
      tested this hypothesis on healthy male FBFN1 rats fed for four weeks with
      isocaloric, 10% fat-containing diets supplemented with 1, 3, or 10% fish oil
      (FO). High resolution mass spectrometric analysis confirmed expected diet-driven
      increases in docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid
      (EPA, 20:5, n-3) in sera, liver and nonsynaptosomal brain mitochondria. We
      further evaluated the resistance of brain and liver mitochondria to Ca(2+)
      overload and prooxidants. Under these conditions, neither mitochondrial
      resistance to Ca(2+) overload and prooxidants nor mitochondrial physiology is
      altered by diet, despite the expected incorporation of DHA and EPA in
      mitochondrial membranes and plasma. Collectively, the data eliminate one of the
      previously proposed mechanism(s) that n-3 PUFA induced augmentation of
      mitochondrial resistance to the oxidant/calcium-driven dysfunction. These data
      furthermore allow us to define a specific series of follow-up experiments to test
      related hypotheses about the effect of n-3 PUFAs on brain mitochondria.

PMID- 22970379
TI  - Current challenges in development of differentially expressed and prognostic
      prostate cancer biomarkers.
AB  - Introduction. Predicting the aggressiveness of prostate cancer at biopsy is
      invaluable in making treatment decisions. In this paper we review the
      differential expression of genes and microRNAs identified through microarray
      analysis as potentially useful markers for prostate cancer prognosis and discuss
      some of the challenges associated with their development. Methods. A review of
      the literature was conducted through Medline. Articles were identified through
      searches of the following terms: "prostate cancer AND differential expression",
      "prostate cancer prognosis", and "prostate cancer AND microRNAs". Results. Though
      numerous differentially expressed genes and microRNAs were identified as possible
      prognostic markers, the significance of several of these genes is either debated
      due to conflicting results or is not validated in other study populations. A few
      of the articles constructed predictive nomograms using a panel of biomarkers
      which require further validation. Challenges to the development of useful markers
      include different methodology, cancer heterogeneity, and sampling error. These
      can be overcome by categorizing prognostic factors into particular gene pathways
      or by supplementing biopsy information with blood or urine-based biomarkers.
      Conclusion. Though biomarkers based on differential expression offer the
      potential to improve decision making concerning prostate cancer, further
      validation of their utility and accuracy at the biopsy level is needed.

PMID- 22970380
TI  - Recent advances in the genetic transformation of coffee.
AB  - Coffee is one of the most important plantation crops, grown in about 80 countries
      across the world. The genus Coffea comprises approximately 100 species of which
      only two species, that is, Coffea arabica (commonly known as arabica coffee) and
      Coffea canephora (known as robusta coffee), are commercially cultivated. Genetic
      improvement of coffee through traditional breeding is slow due to the perennial
      nature of the plant. Genetic transformation has tremendous potential in
      developing improved coffee varieties with desired agronomic traits, which are
      otherwise difficult to achieve through traditional breeding. During the last
      twenty years, significant progress has been made in coffee biotechnology,
      particularly in the area of transgenic technology. This paper provides a detailed
      account of the advances made in the genetic transformation of coffee and their
      potential applications.

PMID- 22970382
TI  - Evaluation of the appropriate age range of colorectal cancer screening based on
      the changing epidemiology in the past 20 years in taiwan.
AB  - Introduction. According to the recommendation of the United States Preventative
      Services Task Force, most countries provide average-risk screening for colorectal
      cancers (CRCs) between the ages of 50 and 75 years. However, the age range of
      screening should be modified because of an increasing life span. Methods. Totally
      124,314 CRC cases were registered in Taiwan Cancer Registry from 1988 to 2007.
      The 20-year study period was divided into four 5-year increments. We divided the
      patients into four age groups (under age 50, age 50-74, age 74-84, and over age
      85) in each increment to determine whether there were changes in the age
      distribution. Results. In the subgroup of patients under age 50, the number of
      CRC cases increased, but they accounted for a decreasing proportion of the total
      CRCs. In the 50-74 age group, the proportion of CRC cases also dropped. In
      contrast, the proportion increased in the 75-84 age group. Therefore, 43.63% of
      CRC patients would not be delegated to screen in the period of 2003-2007 if the
      CRC screening were restricted in the 50-74 age group. Conclusions. CRC screening
      for healthy individuals aged over 75 years is necessary.

PMID- 22970381
TI  - Progress in rectal cancer treatment.
AB  - The dramatic improvement in local control of rectal cancer observed during the
      last decades is to be attributed to attention to surgical technique and to the
      introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse
      remains frequent and is currently insufficiently addressed. Intensification of
      neoadjuvant therapy by incorporating chemotherapy with or without targeted agents
      before the start of (chemo)radiation or during the waiting period to surgery may
      present an opportunity to improve overall survival. An increasing number of
      patients can nowadays undergo sphincter preserving surgery. In selected patients,
      local excision or even a "wait and see" approach may be feasible following active
      neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative
      imaging techniques may in the future allow better selection of patients for this
      treatment option. Controversy persists concerning the selection of patients for
      adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The
      currently available evidence suggests that in complete pathological responders
      long-term outcome is excellent and adjuvant therapy may be omitted. The results
      of ongoing trials will help to establish the ideal tailored approach in
      resectable rectal cancer.

PMID- 22970383
TI  - Independent Predictors of Erectile Dysfunction in Type 2 Diabetes Mellitus: Is It
      True What They Say about Risk Factors?
AB  - Introduction. The aim of this study was to evaluate the independent predictors of
      ED in adult men with type 2 diabetes mellitus (T2DM). Methods. We have recruited
      200 T2DM patients referred to our center between March 1, 2009 and March 1, 2010.
      All the patients were scored with the International Index of Erectile Function
      (IIEF)-5 questionnaires. Contribution of age, body mass index (BMI), smoking,
      blood pressure, lipid profile, fasting plasma glucose (FPG), glycosylated
      hemoglobin (HbA1c), free testosterone concentration, and duration of diabetes to
      risk of ED were evaluated. Results. Of 200 men with T2DM, 59.5% had ED (95%CI:
      52%-67%). A negative significant correlation was found between potency score and
      HbA1c (r: 0.20,P: 0.01), FPG (r: 0.17, P: 0.03) and SBP (r: 0.18, P: 0.02) but
      not between other risk factors such as lipid profile, BMI, and serum testosterone
      level. By using multivariate logistic regression analysis, we found out that the
      only two independent predictors of ED in these group of patients are age (OR:
      2.8, P: 0.01), and taking calcium channel blockers (CCB) (OR: 4.1, P: 0.01).
      Conclusions. Aging and taking CCB were the only two major predictors for ED but
      surprisingly other metabolic or sexual covariates in this study did not have
      predictive value for ED risk in T2DM patients.

PMID- 22970384
TI  - The use of ketogenic diet in pediatric patients with epilepsy.
AB  - A ketogenic diet is a nonpharmacologic treatment strategy to control refractory
      epilepsy in children. Although this diet has been used successfully to reduce
      seizures since the 1920s, the anticonvulsant mechanism of ketosis remains
      unknown. The initiation of the diet requires an average four-day hospitalization
      to achieve ketosis in the patient as well as to provide thorough education on
      diet maintenance for both the patient and the caregivers. A ketogenic diet,
      consisting of low carbohydrate and high fat intake, leaves little room for
      additional carbohydrates supplied by medications. Patients on ketogenic diets who
      exceed their daily carbohydrate limit have the risk of seizure relapse,
      necessitating hospital readmission to repeat the diet initiation process. These
      patients are at a high risk for diversion from the diet. Patients admitted to the
      hospital setting are often initiated on multiple medications, and many hospital
      systems are not equipped with appropriate monitoring systems to prevent
      clinicians from introducing medications with high carbohydrate contents.
      Pharmacists have the resources and the expertise to help identify and prevent the
      initiation of medications with high carbohydrate content in patients on ketogenic
      diets.

PMID- 22970385
TI  - Sexual Knowledge among High School Students in Northwestern Iran.
AB  - Objectives. Regarding the importance of sexual desire in adolescence period and
      public and parental concerns about it and considering the lack of studies on
      sexual knowledge especially in adolescents in Iran, this study was conducted to
      evaluate the sexual issues in high school girls and boys. Patients and Methods.
      The cross-sectional study was performed on 2700 high school students. Students
      were selected through a multi-staged randomized sampling method in Tabriz and by
      the convenience method in Ardabil and Urmia. Data collection tool was a
      questionnaire including knowledge questions and measured by a three-point scale.
      Data were statistically analyzed with SPSS version 11.5 software. Results. 11.8%
      of the students had a low sexual knowledge, 46.7% had average and 41.5% had a
      high one. There was no significant difference between male and female students'
      general sexual knowledge. The highest knowledge was about being aware of the
      religious rules concerning sex. Conclusion. Adolescents should be trained and
      acquire information about the different aspects of sexual issues. Female
      adolescents especially need to be educated about puberty physiology, fertility
      physiology and STDs.

PMID- 22970386
TI  - Retrospective study of Japanese patients with schizophrenia treated with
      aripiprazole.
AB  - Aim. The purpose of this retrospective study was to evaluate changes in clinical
      indicators which influence the quality of life (QOL) of patients with
      schizophrenia treated by antipsychotic therapy before and after switching to
      aripiprazole. Methods. A retrospective chart review of 27 patients diagnosed with
      schizophrenia and who were switched from one antipsychotic to aripiprazole was
      performed. Clinical indicators about the daily dosage of antipsychotics and
      antiparkinsonian drugs, psychiatric condition, and glucose/lipid metabolism,
      clinical evaluation by nursing observation were used to measure the
      responsiveness of subjects to aripiprazole. Results. Of the 27 subjects, 14
      responded to the switch to aripiprazole with significant improvement of the Brief
      Psychiatric Rating Scale (BPRS) score (P = 0.04), significant decrease in dosage
      of antipsychotics in 71% of patients (P = 0.03), and tendency toward reduction in
      dosage of antiparkinsonian drugs (P = 0.07) and body mass index (BMI) (P = 0.06).
      However, 8 of 27 subjects had a significant increase in lipid levels after
      switching to aripiprazole (P = 0.01). Conclusion. QOL for subjects who responded
      to the switch to aripiprazole improved as indicated by lower doses of
      antipsychotic and antiparkinson medications, improvement in BPRS score, and a
      decrease in BMI. Results indicate little influence on patient's QOL.

PMID- 22970387
TI  - Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving
      Protein Homeostasis in Mouse.
AB  - The accumulating evidence demonstrates the essential role of neuregulin-1
      signaling in the adult heart, and, moreover, indicates that an impaired
      neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity.
      Despite this strong data, the specific cardiomyocyte targets of the active
      erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways
      involved in cardiomyocyte damage as a result of the cardiac sensitization to
      anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse.
      We performed morphological analyses to evaluate the ventricular remodeling and
      employed a cDNA microarray to assess the characteristic gene expression profile,
      verified data by real-time RT-PCR, and then grouped into functional categories
      and pathways. We confirm the upregulation of genes related to the classical
      signature of a hypertrophic response, implicating an erbB2-dependent mechanism in
      doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkable
      downregulation of IGF-I/PI-3' kinase pathway and extends our current knowledge by
      uncovering an altered ubiquitin-proteasome system leading to cardiomyocyte
      autophagic vacuolization.

PMID- 22970388
TI  - Detection of PIK3CA Mutations in Breast Cancer Bone Metastases.
AB  - Background. An important goal of personalized cancer therapy is to tailor
      specific therapies to the mutational profile of individual patients. However,
      whole genome sequencing studies have shown that the mutational profiles of
      cancers evolve over time and often differ between primary and metastatic sites.
      Activating point mutations in the PIK3CA gene are common in primary breast cancer
      tumors, but their presence in breast cancer bone metastases has not been assessed
      previously. Results. Fourteen patients with breast cancer bone metastases were
      biopsied by three methods: CT-guided bone biopsies; bone marrow trephine
      biopsies; and bone marrow aspiration. Samples that were positive for cancer cells
      were obtained from six patients. Three of these patients had detectable PIK3CA
      mutations in bone marrow cancer cells. Primary tumor samples were available for
      four of the six patients assessed for PIK3CA status in their bone metastases. For
      each of these, the PIK3CA mutation status was the same in the primary and
      metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer
      bone metastases. The PIK3CA mutation status in bone metastases samples appears to
      reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients
      with bone metastases may be candidates for treatment with selective PIK3CA
      inhibitors.

PMID- 22970391
TI  - Recent progress in understanding plasticity in neurogenetic disorders.

PMID- 22970390
TI  - Plasticity of the dorsal "spatial" stream in visually deprived individuals.
AB  - Studies on visually deprived individuals provide one of the most striking
      demonstrations that the brain is highly plastic and is able to rewire as a
      function of the sensory input it receives from the environment. In the current
      paper, we focus on spatial abilities that are typically related to the dorsal
      visual pathway (i.e., spatial/motion processing). Bringing together evidence from
      cataract-reversal individuals, early- and late-blind individuals and sight
      recovery cases of long-standing blindness, we suggest that the dorsal "spatial"
      pathway is mostly plastic early in life and is then more resistant to subsequent
      experience once it is set, highlighting some limits of neuroplasticity.

PMID- 22970389
TI  - Age-related decline in controlled retrieval: the role of the PFC and sleep.
AB  - Age-related cognitive impairments often include difficulty retrieving memories,
      particularly those that rely on executive control. In this paper we discuss the
      influence of the prefrontal cortex on memory retrieval, and the specific memory
      processes associated with the prefrontal cortex that decline in late adulthood.
      We conclude that preretrieval processes associated with preparation to make a
      memory judgment are impaired, leading to greater reliance on postretrieval
      processes. This is consistent with the view that impairments in executive control
      significantly contribute to deficits in controlled retrieval. Finally, we discuss
      age-related changes in sleep as a potential mechanism that contributes to
      deficiencies in executive control that are important for efficient retrieval. The
      sleep literature points to the importance of slow-wave sleep in restoration of
      prefrontal cortex function. Given that slow-wave sleep significantly declines
      with age, we hypothesize that age-related changes in slow-wave sleep could
      mediate age-related decline in executive control, manifesting a robust deficit in
      controlled memory retrieval processes. Interventions, like physical activity,
      that improve sleep could be effective methods to enhance controlled memory
      processes in late life.

PMID- 22970392
TI  - Multiple pulp stones in primary and developing permanent dentition: a report of 4
      cases.
AB  - Pulp stones are foci of calcification or discrete calcifications in the dental
      pulp. They are frequently found on bitewing and periapical radiographs, but their
      occurrence in entire dentition is unusual. We are reporting four cases in which
      the occurrence of pulp stones ranged from their presence in just primary teeth
      (Cases 1 and 2) to involvement of young permanent teeth also (Case 3) and even
      unerupted permanent teeth (Case 4). In all the cases, dental, medical, and family
      histories as well as the findings from the clinical examination of the patient
      were not contributory. Histopathological report revealed true denticle. Metabolic
      evaluation of patients through liver function test, kidney function test, and
      blood investigation did not show any metabolic disorders. Patients were also
      evaluated for any systemic, syndromic, or genetic involvement, but this was also
      noncontributing. Therefore, it is suggested that these unusual cases may be of
      idiopathic origin.

PMID- 22970393
TI  - A poor prognostic case of mucoepidermoid carcinoma of the thyroid: a case report.
AB  - Mucoepidermoid carcinoma (MEC) of the thyroid is very rare and low-grade indolent
      neoplasm. In past reports of the thyroid MEC, only seven cases were described as
      poor prognosis. A 91-year-old woman presented with a rapidly growing mass of the
      left upper neck. She was followed thyroid papillary carcinoma (PC) without
      operation for two years. Fine needle aspiration cytology (FNAC) showed
      undifferentiated cells. Total thyroidectomy and bilateral neck dissection were
      performed. In pathological findings, the tumor had two areas of MEC and PC. The
      boundary of them was mixed. She died of multiple lung metastases only after four
      months from the operation. We report a rare case of thyroid MEC which had an
      aggressive behavior and poor prognosis. This case is a precious in that thyroid
      MEC occurred during observation of PC and suggests a possibility of the
      transformation from PC to MEC.

PMID- 22970394
TI  - Gastric duplication: a rare cause of massive lower gastrointestinal haemorrhage,
      chest wall mass, and enterocutaneous fistula.
AB  - Gastric duplications are uncommon developmental abnormality reported to present
      with different clinical scenarios. We present a 2-1/2-year-old Nigerian female
      who started having intermittent massive lower gastrointestinal haemorrhage at 5
      months of age. She subsequently developed a lower chest wall mass and
      enterocutaneous fistula. She was found to have gastric duplication with fistulous
      communication with the descending colon, spleen, and lower chest wall. To the
      best of our knowledge, this is the first paper on gastric duplication resulting
      in intermittent massive lower gastrointestinal bleeding mainly from splenic
      capsular erosion and fistula and enterocutaneous fistula resulting from erosion
      of anterior abdominal wall. Gastric duplication is hence an important rare cause
      of intermittent massive lower gastrointestinal haemorrhage and spontaneous
      enterocutaneous fistula in the paediatric population.

PMID- 22970396
TI  - Prophylactic breast bud radiotherapy for patients taking bicalutamide: should
      this still be practised for patients with prostate cancer?
AB  - Prophylactic breast bud radiotherapy is used to prevent gynaecomastia and
      mastalgia in patients with prostate cancer who are being treated with
      antiandrogen and oestrogen therapy. Here a case is presented of a patient who
      developed soft-tissue sarcoma of the breast subsequent to breast bud radiotherapy
      prior to bicalutamide hormone treatment. Bicalutamide is often prescribed for
      younger men in the adjuvant setting or as monotherapy for locally advanced
      disease. The data regarding the efficacy of prophylactic breast bud radiotherapy
      is reviewed, and it is proposed that alternative therapies should be considered
      such as tamoxifen.

PMID- 22970397
TI  - Obstructive Sleep Apnea in a Patient with CHARGE Syndrome.
AB  - CHARGE syndrome is a genetic disorder characterized by choanal atresia, coloboma
      of the eye, and ear and cranial nerve abnormalities. We report a child with
      CHARGE syndrome and obstructive sleep apnea. We highlight difficulties in
      discerning obstructive sleep apnea-related symptoms from typical features of
      CHARGE syndrome. Treatment options are discussed with regard to our patient.
      Tonsillectomy and adenoidectomy improved physical symptoms of obstructive sleep
      apnea in the patient.

PMID- 22970395
TI  - Combined unilateral hemilaminectomy and thoracoscopic resection of the dumbbell
      shaped thoracic neurinoma: a case report.
AB  - A 41-year-old woman complained of chest pain when coughing. Computed tomography
      and magnetic resonance imaging disclosed a homogenously enhanced tumor occupying
      the spinal canal at the Th7 level and extending into the right paravertebral
      space through the intervertebral foramen between Th7 and Th8. The tumor was
      successfully removed via a posterolateral approach using unilateral
      hemilaminectomy followed by thoracoscopic surgery. Since the tumor had a dumbbell
      shape, a combined approach was considered essential. The histological diagnosis
      was a thoracic neurinoma. Combined hemilaminectomy and thoracoscopic surgery may
      be a good alternative for the management of thoracic dumbbell-shaped tumors.

PMID- 22970398
TI  - Religious beliefs, possession States, and spirits: three case studies from sri
      lanka.
AB  - We describe three patients from different religious backgrounds in Sri Lanka
      whose possession states were strongly influenced by their religious beliefs.
      Patient A was a Buddhist who claimed to have special powers given by a local
      deity named Paththini. Patient B was a Catholic who experienced spirits around
      her whom she believed were sent by Satan. Patient C was a Muslim and believed she
      was possessed by spirits. The religious beliefs also influenced the help-seeking
      behaviour and the rituals or treatments to which they responded.

PMID- 22970399
TI  - Development of Bullous Disease during Treatment of Pulmonary Marginal Zone B-Cell
      Lymphoma.
AB  - We describe an unusual case of severe pulmonary bullous disease developing during
      treatment of marginal zone B-Cell lymphoma (MALT) involving the pulmonary
      parenchyma. The patient originally presented with pneumonia-like symptoms along
      with hemoptysis and was diagnosed with MALT lymphoma after a video-assisted
      thoracic surgical (VATS) lung biopsy. Computed tomography (CT) of the chest at
      diagnosis revealed multiple opacities, but no bullous disease. During the ensuing
      4 years, and while on chemotherapy for the MALT lymphoma, sequential CT and
      pulmonary function tests revealed the development of progressive bullous disease
      resulting in the replacement of large portions of the lung parenchyma with
      bilateral bullae. This complication is rare, has been reported only once before
      in a patient with concomitant amyloidosis, and may be related to activation of
      proteolytic enzymes by lymphoma cells or chemotherapeutic agents.

PMID- 22970400
TI  - A rare case of hemoptysis: intrapulmonary cavitary lesion appearing as a thoracic
      endometriosis.
AB  - Pulmonary endometriosis is a rarely seen disease of the lung. On computed
      tomography, a cavitary lesion of 15 * 26 in size was detected in the lung
      parenchyma of a 38-year-old female patient who was examined due to hemoptysis.
      The pathologic result of the surgically excised cavitary lesion was reported as
      pulmonary endometriosis.

PMID- 22970401
TI  - Necrolytic migratory erythema as the first manifestation of glucagonoma.
AB  - Necrolytic migratory erythma (NME) as a rare skin disorder that can affected
      Perineum, distal extremities, lower abdomen and face are the most commonly
      affected sites.It can be as a part of Glucagonoma syndrome that is defined as an
      association of glucagonoma with NME, hyperglucagonemia, glucose intolerance,
      anemia and weight loss. Here, Authors describe a woman admitted to the
      dermatology ward with NME which was later found to be associated with glucagonoma
      and multiple hepatic lesions.

PMID- 22970402
TI  - Metastatic renal cell carcinoma change vascularity.
AB  - Several molecular targeted agents have been approved for clinical use for
      metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC
      is presented. These tumors could change vascularity by administration of
      molecular agents. We could select a drug timely based on findings of computed
      tomography. To our knowledge, this is the first report that tumor's character
      change induced by molecular targeted agents can be detected and the efficacy of
      molecular targeted agents can be predicted.

PMID- 22970403
TI  - Current status of mechanical circulatory support: a systematic review.
AB  - Heart failure is a major public health problem and its management requires a
      significant amount of health care resources. Even with administration of the best
      available medical treatment, the mortality associated with the disease remains
      high. As therapeutical strategies for heart failure have been refined, the number
      of patients suffering from the disease has expanded dramatically. Although heart
      transplantation still represents the gold standard therapeutical approach, the
      implantation of mechanical circulatory support devices (MCSDs) evolved to a well
      established management for this disease. The limited applicability of heart
      transplantation caused by a shortage of donor organs and the concurrent expand of
      the patient population with end-stage heart failure led to a considerable
      utilization of MCSDs. This paper outlines the current status of mechanical
      circulatory support.

PMID- 22970405
TI  - The contribution of the amyloid hypothesis to the understanding of Alzheimer's
      disease: a critical overview.

PMID- 22970404
TI  - Bicuspid aortic valve and thoracic aortic aneurysm: three patient populations,
      two disease phenotypes, and one shared genotype.
AB  - Bicuspid aortic valve (BAV) and thoracic aortic aneurysm (TAA) are two discrete
      cardiovascular phenotypes characterized by latent progressive disease states.
      There is a clear association between BAV and TAA; however the nature and extent
      of this relationship is unclear. There are both distinct and overlapping
      developmental pathways that have been established to contribute to the formation
      of the aortic valve and the aortic root, and the mature anatomy of these
      different tissue types is intimately intertwined. Likewise, human genetics
      studies have established apparently separate and common contributions to these
      clinical phenotypes, suggesting complex inheritance and a shared genetic basis
      and translating 3 patient populations, namely, BAV, TAA, or both, into a common
      but diverse etiology. A better understanding of the BAV-TAA association will
      provide an opportunity to leverage molecular information to modify clinical care
      through more sophisticated diagnostic testing, improved counseling, and
      ultimately new pharmacologic therapies.

PMID- 22970407
TI  - Association between Serum Uric Acid Levels and Sleep Variables: Results from the
      National Health and Nutrition Survey 2005-2008.
AB  - Sleep disordered breathing as well as high serum uric acid levels are independent
      risk factors for cardiovascular disease. However, studies evaluating the
      relationship between sleep-disordered breathing and hyperuricemia are limited. We
      examined the 2005-2008 National Health and Nutrition Examination survey's sleep
      variables and high serum uric acid among 6491 participants aged >=20 years. The
      sleep variables included sleep duration, snoring, snorting, and daytime
      sleepiness. The main outcome was high serum uric acid level, defined as levels of
      serum uric acid >6.8 mg/dL in males and >6.0 mg/dL in females. We found that
      snoring more than 5 nights per week, daytime sleepiness, and an additive
      composite score of sleep variables were associated with high serum uric acid in
      the age- , sex-adjusted model and in a multivariable model adjusting for
      demographic and lifestyle/behavioral risk factors. The association was attenuated
      with the addition of variables related to clinical outcomes such as depression,
      diabetes, hypertension, and high-cholesterol levels. Our results indicate a
      positive relationship between sleep variables, including the presence of snoring,
      snorting, and daytime sleepiness, and high serum uric acid levels.

PMID- 22970406
TI  - Lysosomal fusion dysfunction as a unifying hypothesis for Alzheimer's disease
      pathology.
AB  - Alzheimer's disease is characterized pathologically by extracellular senile
      plaques, intracellular neurofibrillary tangles, and granulovacuolar degeneration.
      It has been debated whether these hallmark lesions are markers or mediators of
      disease progression, and numerous paradigms have been proposed to explain the
      appearance of each lesion individually. However, the unfaltering predictability
      of these lesions suggests a single pathological nidus central to disease onset
      and progression. One of the earliest pathologies observed in Alzheimer's disease
      is endocytic dysfunction. Here we review the recent literature of endocytic
      dysfunction with particular focus on disrupted lysosomal fusion and propose it as
      a unifying hypothesis for the three most-studied lesions of Alzheimer's disease.

PMID- 22970408
TI  - Bone mineral density in spinal cord injury: an evaluation of the distal femur.
AB  - Osteoporosis (OP) in spinal cord injury (SCI) patients is a secondary process in
      which numerous factors are involved. Diagnosing OP and the threshold for
      fractures in this population, based on bone mineral density (BMD) measured by
      double energy X-ray absorptiometry (DXA), is still a challenge. The aim of this
      study was to evaluate bone mineral loss by DXA, its relationship with body
      composition and fracture incidence, in complete paraplegics patients, compared
      with aged-matched controls; we include a nonstandard bone site, the distal femur,
      and describe the technical and practical aspects of this procedure. Twenty-five
      SCI patients were included in the study and 17 subjects as control group. No
      prior or recent fractures were observed in X-ray analysis. The BMD of all femoral
      sites was significantly lower in patients than in controls (femoral neck, total
      femur, and distal femur); no difference was observed between BMD of the lumbar
      spine of patients and controls. We found inverse relationship between time of SCI
      and bone mineral mass only for distal femur BMD. We conclude that the distal
      femur is a more sensitive bone site for assessing bone loss by DXA, in SCI
      patients, than the proximal femoral sites.

PMID- 22970409
TI  - P2X7 Receptor Function in Bone-Related Cancer.
AB  - Modulation of tumor microenvironment by different mediators is central in
      determining neoplastic formation and progression. Among these molecules
      extracellular ATP is emerging as a good candidate in promoting cell growth,
      neovascularization, tumor-host interactions, and metastatization. This paper
      summarizes recent findings on expression and function of P2X7 receptor for
      extracellular ATP in primary and metastatic bone cancers. Search of mRNA
      expression microchip databases and literature analysis demonstrate a high
      expression of P2X7 in primary bone tumors as well as in other malignancies such
      as multiple myeloma, neuroblastoma, breast, and prostate cancer. Evidence that
      P2X7 triggers NFATc1, PI3K/Akt, ROCK, and VEGF pathways in osteoblasts promoting
      either primary tumor development or osteoblastic lesions is also reported.
      Moreover, P2X7 receptor is involved in osteoclast differentiation, RANKL
      expression, matrix metalloproteases and cathepsin secretion thus promoting bone
      resorption and osteolytic lesions. Taken together these data point to a pivotal
      role for the P2X7 receptor in bone cancer biology.

PMID- 22970410
TI  - Thyroid surgery for elderly patients: are they at increased operative risks?
AB  - An increasing elderly population, a rising incidence of differentiated thyroid
      carcinoma (DTC), and a rising incidence of benign nodular disease with age are
      all contributing to a rise in thyroid operations for the elderly. Literature
      review on the outcome and safety of thyroid surgery in elderly patients has been
      filled with conflicting results and this subject remains controversial. Although
      most single-institution studies conducted by high-volume surgeons did not find
      significant differences of complication rates in elderly when compared with
      younger cohorts, they often lacked the power necessary to identify subtle
      differences and suffered from various selection and referral biases. Recent
      evidence from large population-based studies concluded that thyroid surgery in
      the elderly was associated with higher complication rates. One of the major
      contributing factors for the increased complication rate was because most elderly
      patients suffered from many preexisting comorbidities. Therefore, elderly
      patients who have abnormal thyroid findings should complete a thorough
      preoperative workup and better postoperative care after undergoing any thyroid
      surgery. Furthermore, these high-risk patients would benefit if they could be
      referred to high-volume, specialized surgical units early. In this systemic
      review, we aimed to evaluate different issues and controversies in thyroidectomy
      for elderly patients.

PMID- 22970411
TI  - Parkinson's disease: leucine-rich repeat kinase 2 and autophagy, intimate
      enemies.
AB  - Parkinson's disease is the second common neurodegenerative disorder, after
      Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine
      generating cells in the substancia nigra, a region of the midbrain. The etiology
      of Parkinson's disease has long been through to involve both genetic and
      environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause
      late-onset Parkinson's disease with a clinical appearance indistinguishable from
      Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism
      whereby a cell recycles or degrades damage proteins and cytoplasmic organelles.
      This degradative process has been associated with cellular dysfunction in
      neurodegenerative processes including Parkinson's disease. We discuss the role of
      leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this
      degradative mechanism in cells can be implicated in the Parkinson's disease
      etiology.

PMID- 22970413
TI  - Welcome to the new members of the editorial board.

PMID- 22970414
TI  - Translational research: where do we go?

PMID- 22970412
TI  - Neuropsychiatric symptoms in Parkinson's disease with mild cognitive impairment
      and dementia.
AB  - Neuropsychiatric symptoms commonly complicate Parkinson's disease (PD), however
      the presence of such symptoms in mild cognitive impairment (PD-MCI) specifically
      has not yet been well described. The objective of this study was to examine and
      compare the prevalence and profile of neuropsychiatric symptoms in patients with
      PD-MCI (n = 48) to those with PD and no cognitive impairment (PD-NC, n = 54) and
      to those with dementia in PD (PDD, n = 25). PD-MCI and PDD were defined using
      specific consensus criteria, and neuropsychiatric symptoms were assessed with the
      12-item Neuropsychiatric Inventory (NPI). Self-rated apathy, depression, and
      anxiety rating scales were also administered. Over 79% of all participants
      reported at least one neuropsychiatric symptom in the past month. The proportion
      in each group who had total NPI scores of >=4 ("clinically significant") was as
      follows: PD-NC, 64.8%; PD-MCI, 62%; PDD 76%. Apathy was reported in almost 50% of
      those with PD-MCI and PDD, and it was an important neuropsychiatric symptom
      differentiating PD-MCI from PD-NC. Psychosis (hallucinations and delusions)
      increased from 12.9% in PD-NC group; 16.7% in PD-MCI group; and 48% in PDD group.
      Identifying neuropsychiatric symptoms in PD-MCI may have implications for
      ascertaining conversion to dementia in PD.

PMID- 22970415
TI  - Evidence-based changes in devices and methods of endovascular recanalization
      therapy.
AB  - The devices and methods of endovascular recanalization therapy (ERT) have been
      rapidly developed and changed since PROACT II trial. Emerging as a treatment
      option in addition to intravenous or intra-arterial thrombolysis, mechanical
      thrombectomy is currently being further developed and investigated as a potential
      first-line and stand-alone treatment. This review highlights and summarizes the
      recent clinical series and trials of the available devices and methods of ERT
      focusing on the multimodal approach.

PMID- 22970416
TI  - Silent microembolism on diffusion-weighted MRI after coil embolization of
      cerebral aneurysms.
AB  - PURPOSE: The purpose of this study was to investigate the frequency and risk
      factors of procedure-related thromboembolism on diffusion-weighted imaging (DWI)
      associated with aneurysmal coil embolization. MATERIALS AND METHODS: We
      prospectively evaluated 39 consecutive patients with a cerebral aneurysm with DWI
      after coil embolization. All hyperintense lesions on DWI with a drop of apparent
      diffusion coefficient values were classified into acute thromboembolic infarction
      (larger than 5 mm in maximal diameters, and located in the vascular territory of
      the parent artery) and silent microembolism (single or multiple tiny dot-like
      lesion, less than 5 mm, usually 1-2 mm in size). Possible risk factors for
      thromboembolic events included vascular risk factors, aneurysmal factors, and
      procedure-related factors. RESULTS: Hyperintense lesions on DWI were seen in 17
      (43.6%) patients and symptomatic DWI positive lesions were four (10.3%). Acute
      thromboembolic infarction was observed in seven (17.9%) patients and silent
      microembolism in 14 (35.9%) patients. Numbers of silent microembolism ranged from
      1 to 15 (mean: 2.86, standard deviation: 3.74). Silent microembolisms were
      located at ipsilateral (n=3, 21.4%), contralateral (n=5, 35.7%), bilateral (n=4,
      28.6%), and not related (n=2, 14.3%) to the procedure site. There were no
      statistical significant risk factors in acute thromboembolic infarction. However,
      incidence of silent microembolisms was significantly correlated with left side
      approach (odds ratio, 4.44, 95% confidence interval, 1.08-18.36; P=0.03).
      CONCLUSION: Left side approach may have increased the likelihood of asymptomatic
      multiple scattered microemboli after aneurysmal coiling procedures. Particular
      care must be taken in the handling of guiding catheters, especially when proving
      left side great vessels.

PMID- 22970417
TI  - Endovascular Embolization of Intracranial Aneurysms Using Bare Platinum AxiumTM
      Detachable Coils: Immediate and Short-Term Follow-up Results from a Multicenter
      Registry.
AB  - PURPOSE: AxiumTM coils were developed to improve the durability of coil-embolized
      cerebral aneurysms by increasing packing density. The purpose of this prospective
      multicenter registry was to evaluate the safety and durability of AxiumTM coils.
      MATERIALS AND METHODS: One hundred twenty-six patients with 135 aneurysms of <=
      15 mm in size underwent coil embolization using bare platinum coils, with AxiumTM
      coils constituting over 50% of the total coil length. Immediate and short-term
      follow-up results were prospectively registered and retrospectively evaluated.
      RESULTS: Of the 135 aneurysms (83 unruptured and 52 ruptured), immediate post
      embolization angiography revealed complete occlusion in 80 aneurysms (59.3%),
      neck remnants in 47 (34.8%), and incomplete occlusion in 8 (5.9%). The mean
      packing density was 42.8% (range, 9.5 - 90%) with AxiumTM coil length
      constituting a mean of 87.9% of total coil length. The rate of procedure-related
      complications was 16.3%. Procedure-related permanent morbidity and mortality
      rates were 3.2% and 0.8%, respectively. Follow-up catheter or MR angiography,
      which was available in 101 aneurysms at 6 - 15 months (mean, 7.7 months),
      revealed stable or improved occlusion in 95 aneurysms and worsening in 6
      aneurysms (5.9%). Lower packing density (< 30%) remained the only predictor for
      anatomical worsening on multivariable logistic regression analysis (P < 0.05).
      CONCLUSION: In this registry, AxiumTM coils showed a relatively low rate of
      anatomical worsening on short-term follow-up imaging with an acceptable
      periprocedural safety profile compared to reports of other platinum coils. These
      results may warrant further study of long-term durability with AxiumTM coils in
      larger populations.

PMID- 22970418
TI  - Endovascular Treatment of Wide-necked Cerebral Aneurysms with an Acute Angle
      Branch Incorporated into the Sac: Novel methods of Branch Access in 8 Aneurysms.
AB  - PURPOSE: The optimal management of geometrically complex aneurysms remains
      challenging. The aim of this retrospective study was to evaluate the safety and
      feasibility of branch-selective technique (BT) in wide-necked aneurysms with an
      acute angle branch incorporated into the sac. MATERIALS AND METHODS: Eight
      consecutive patients harboring wide-necked cerebral aneurysms with an
      incorporated, acute angle branch (mean, 30.4 degrees ) underwent coiling over an
      18-month period. Dome-to-neck ratio ranged from 0.9 to 1.8 (mean, 1.2). Every
      procedure utilized BT, i.e., stent- or catheter-assisted coiling through the
      incorporated branch. RESULTS: Technical success was achieved in all cases. With
      the aim to avoid the risk of aneurysmal rupture during struggling intraaneurysmal
      wire navigation, a 'looping method' and retrograde approach of a preshaped 0.014'
      microcatheter (C or J) was used for branch access in five cases and a 'looping
      method' and antegrade approach in one case. In the remaining one, just the C
      preshape was enough to directly enter the branch without intraaneurysmal wire
      navigation. Overall, stent-assisted coiling was performed in seven cases, while
      catheter-assisted coiling was undertaken in one. The only complication was
      thrombotic posterior inferior cerebellar artery occlusion in one case, which was
      recanalized after tirofiban infusion. New neurological deficits were not
      identified in any cases. CONCLUSION: BT seems safe and feasible for wide-necked
      aneurysms with an acute angle branch incorporated into the sac. The looping
      method may offer safe access to the incorporated, acute angle branch and should
      be considered for replacement of the fearful intra-aneurysmal wire navigation.

PMID- 22970419
TI  - Mechanism of procedural failure related to wingspan.
AB  - PURPOSE: Wingspan is the only FDA approved self-expanding stent for intracranial
      artery and known to have better delivery compared to balloon expandable stent.
      However, some delivery failure has been reported but incidence and mechanism of
      the failure have not been completely elucidated. We present the cause and
      mechanism of Wingspan deployment failure experienced in our Institute. MATERIALS
      AND METHODS: We experienced deployment failure in seven patients (8.8%) out of 80
      patients who underwent Wingspan stenting since 2007. Mean age of the patients was
      62 (range 47~78) and male to female ratio was 6:1. We evaluated the cause and
      mechanism why the deployment was not successful and how we could manage it
      subsequently. RESULTS: WE CATEGORIZED FAILURES OCCURRED IN SEVEN PATIENTS INTO
      THREE CATEGORIES: delivery failure (n = 3), deployment failure of stent (n = 3),
      retrieval failure of dual tapered (olive) tip of the inner body through the
      deployed the stent (n = 1). The technical failure in using Wingspan stent
      (delivery, deployment and retrieval failures) are related to tortuousness of the
      proximal (n =4) as well as distal (n =1) cerebral vessels to the stenotic lesion
      and bulky profile of the olive tip (n =2). CONCLUSION: The technical failure in
      using Wingspan stent (delivery, deployment and retrieval failures) are related to
      tortuousness of the proximal as well as distal cerebral vessels to the stenotic
      lesion and bulky profile of the olive tip. To avoid device-related complication,
      complete understanding of the stent design is mandatory before using the stent.

PMID- 22970420
TI  - Endovascular intervention for repositioning the distal catheter of ventriculo
      atrial shunt.
AB  - Displacement of distal ventriculo-atrial (VA) shunt is not uncommon. However,
      misplacement of the distal catheter of VA shunt in the internal jugular vein is a
      possibility, especially when conducted without intraoperative monitoring. We
      describe a patient in whom a VA shunt was performed due to failure of ventriculo
      peritoneal shunt and the distal catheter of the shunt was found to be misplaced
      in the left internal jugular vein. Endovascular intervention via femoral vein was
      used to retrieve the distal catheter.

PMID- 22970421
TI  - Late spontaneous recanalization of chronic middle cerebral artery occlusion.
AB  - Early spontaneous recanalization of the middle cerebral artery in acute ischemic
      phase artery is not uncommon, whereas the late spontaneous recanalization of
      chronic occluded artery is a very rare phenomenon and exact incidence and the
      timing of this event have not been quantified. We present a case in which late
      spontaneous recanalization of long-lasting middle cerebral artery occlusion
      occurred in the absence of surgical, endovascular and thrombolytic treatments.

PMID- 22970422
TI  - Asthma Research for All of the United States.
AB  - Asthma disproportionally affects different ethnic/racial groups, with Puerto
      Ricans and African Americans suffering the highest asthma prevalence and
      morbidity, Mexicans the lowest, and non-Hispanic whites in between. Genome-wide
      association studies of asthma have found both shared and race/ethnic-specific
      genetic risks factors for asthma. However, the majority of genetic asthma
      research is performed in populations of European descent, which limits the
      benefits of genetic research to European populations. It is important to
      biomedical and clinical research to include more diverse and underrepresented
      populations. The rich genetic diversity of all populations can be leveraged to
      scientific advantage. For example, admixture mapping provides a more powerful
      approach than traditional genome-wide allelic association studies in discovering
      genetic associations for complex diseases. By being more inclusive we can achieve
      a better understanding of the genetics of asthma, address health disparities, and
      ensure that scientific advances will benefit populations worldwide.

PMID- 22970423
TI  - The Relationship between Asthma and Obesity in Urban Early Adolescents.
AB  - Asthma and obesity, which have reached epidemic proportions, impact urban youth
      to a great extent. Findings are inconsistent regarding their relationship; no
      studies have considered asthma management. We explored the association of obesity
      and asthma-related morbidity, asthma-related health care utilization, and asthma
      management in urban adolescents with uncontrolled asthma. We classified 373 early
      adolescents (mean age=12.8 years; 82% Hispanic or Black) from New York City
      public middle schools into 4 weight categories: normal (body mass index
      [BMI]<85th percentile); overweight (85th percentile<=BMI<95th percentile); obese
      (95th percentile<=BMI<97th percentile); and very obese (BMI>=97th percentile). We
      compared sample obesity prevalence to national estimates, and tested whether
      weight categories predicted caregiver reported asthma outcomes, adjusting for age
      and race/ethnicity. Obesity prevalence was 37%, with 28% of the sample being very
      obese; both rates were significantly higher than national estimates. We found no
      significant differences in asthma-related health care utilization or asthma
      management between weight categories, and a few differences in asthma-related
      morbidity. Relative to normal weight and obese youth, overweight youth had higher
      odds of never having any days with asthma-related activity limitations. They also
      had higher odds of never having asthma-related school absences compared with
      obese youth. Overweight youth with asthma-related activity limitations had more
      days with limitations compared with normal weight youth. Overweight, but not
      obese youth, missed more school due to asthma than normal weight youth.
      Overweight and obesity prevalence was very high in urban, Hispanic, and Black
      adolescents with uncontrolled asthma, but not strongly associated with asthma
      related morbidity, asthma-related health care utilization, or asthma management
      practices.

PMID- 22970425
TI  - A colorimetric and fluorescent dual probe for specific detection of cysteine
      based on intramolecular nucleophilic aromatic substitution.
AB  - 4-Nitro-1,8-naphthalic anhydride (NNA) was used to distinguish cysteine from
      homocysteine and other potentially interfering thiols through a novel sequential
      substitution mechanism. The discrimination involves a blue-fluorescent thioether
      formation via nucleophilic aromatic substitution of the nitro group by thiol,
      followed by a second intramolecular nucleophilic aromatic substitution of
      alkylthio with the amino group to give the green-fluorescent 4-amino derivative.
      NNA is highly selective towards Cys, and the detection limit of Cys by this
      method is 0.3 MUM.

PMID- 22970426
TI  - Optimization of multiplexed PCR on an integrated microfluidic forensic platform
      for rapid DNA analysis.
AB  - This study reports the design, prototyping, and assay development of multiplexed
      polymerase chain reaction (PCR) on a plastic microfluidic device. Amplification
      of 17 DNA loci is carried out directly on-chip as part of a system for continuous
      workflow processing from sample preparation (SP) to capillary electrophoresis
      (CE). For enhanced performance of on-chip PCR amplification, improved control
      systems have been developed making use of customized Peltier assemblies, valve
      actuators, software, and amplification chemistry protocols. Multiple enhancements
      to the microfluidic chip design have been enacted to improve the reliability of
      sample delivery through the various on-chip modules. This work has been enabled
      by the encapsulation of PCR reagents into a solid phase material through an
      optimized Solid Phase Encapsulating Assay Mix (SPEAM) bead-based hydrogel
      fabrication process. SPEAM bead technology is reliably coupled with precise
      microfluidic metering and dispensing for efficient amplification and subsequent
      DNA short tandem repeat (STR) fragment analysis. This provides a means of on-chip
      reagent storage suitable for microfluidic automation, with the long shelf-life
      necessary for point-of-care (POC) or field deployable applications. This paper
      reports the first high quality 17-plex forensic STR amplification from a
      reference sample in a microfluidic chip with preloaded solid phase reagents, that
      is designed for integration with up and downstream processing.

PMID- 22970424
TI  - Genomic Determinants of PI3K Pathway Inhibitor Response in Cancer.
AB  - The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in cancer as
      a result of genetic (e.g., amplifications, mutations, deletions) and epigenetic
      (e.g., methylation, regulation by non-coding RNAs) aberrations targeting its key
      components. Several lines of evidence demonstrate that tumors from different
      anatomical sites depend on the continued activation of this pathway for the
      maintenance of their malignant phenotype. The PI3K pathway therefore is an
      attractive candidate for therapeutic intervention, and inhibitors targeting
      different components of this pathway are in various stages of clinical
      development. Burgeoning data suggest that the genomic features of a given tumor
      determine its response to targeted small molecule inhibitors. Importantly,
      alterations of different components of the PI3K pathway may result in distinct
      types of dependencies and response to specific therapeutic agents. In this
      review, we will focus on the genomic determinants of response to PI3K, dual
      PI3K/mechanistic target of rapamycin (mTOR), mTOR, and AKT inhibitors in cancer
      identified in preclinical models and clinical trials to date, and the development
      of molecular tools for the stratification of cancer patients.

PMID- 22970427
TI  - Highly sensitive label-free colorimetric sensing of nitrite based on etching of
      gold nanorods.
AB  - A simple colorimetric method with high sensitivity and selectivity was developed
      for sensing of nitrite as low as 4.0 MUM by naked eyes, which is based on etching
      of gold nanorods accompanied by shape changes in aspect ratios (length/width) and
      a visible color change from bluish green to red and then to colorless with the
      increase of nitrite.

PMID- 22970428
TI  - A novel fluorescence derivatization method combined with HPLC for determining the
      activities of endogenous caspase.
AB  - A novel fluorescence derivatization method combined with HPLC was developed to
      detect the activity of caspase-3 and -8 in two cell lines (Hela cells and A549
      cells) which were activated by low temperature-assisted ultraviolet irradiation
      (LT-UV), mitomycin C (MMC) and camptothecin during the apoptosis, respectively.
      Two peptide substrates for either caspase-3 or -8 were designed, of which peptide
      fragments were obtained by enzymatic modification, followed by fluorescence
      derivatization. A single fluorescent product was formed when a peptide was heated
      at 120  degrees C for 10 min in a neutral aqueous medium (pH 7.0) containing
      catechol, sodium periodate and sodium borate. Commercial kits for detecting the
      activity of caspase-3 and -8 were used as a control. The relative activity of the
      caspases detected by fluorescence derivatization was similar to that obtained by
      commercial kits, which indicated that the novel method is reliable. The activity
      assays of recombinant human caspases showed that the novel method provided higher
      selectivity than that of commercial kits, which proved it to be more accurate for
      determining the activity of caspases in apoptosis.

PMID- 22970429
TI  - Implementation of a semi-automated strategy for the annotation of metabolomic
      fingerprints generated by liquid chromatography-high resolution mass spectrometry
      from biological samples.
AB  - Metabolomics aims at detecting and semi-quantifying small molecular weight
      metabolites in biological samples in order to characterise the metabolic changes
      resulting from one or more given factors and/or to develop models based on
      diagnostic biomarker candidates. Nevertheless, whatever the objective of a
      metabolomic study, one critical step consists in the structural identification of
      mass spectrometric features revealed by statistical analysis and this remains a
      real challenge. Indeed, this requires both an understanding of the studied
      biological system, the correct use of various analytical information (retention
      time, molecular weight experimentally measured, isotopic golden rules, MS/MS
      fragment pattern interpretation...), or querying online databases. In gas
      chromatography-electro-ionisation (EI)-mass spectrometry, EI leads to a very
      reproducible fragmentation allowing establishment of universal EI mass spectra
      databases (for example, the NIST database -National Institute of Standards and
      Technology) and thus facilitates the identification step. Unfortunately, the
      situation is different when working with liquid chromatography-mass spectrometry
      (LC-MS) since atmospheric pressure ionisation exhibits high inter-instrument
      variability regarding fragmentation. Therefore, the constitution of LC-MS "in
      house" spectral databases appears relevant in this context. The present study
      describes the procedure developed and applied to increment 133 and 130
      metabolites in databanks dedicated to analyses performed with LC-HRMS in positive
      and negative electrospray ionisation, and the use of these databanks for
      annotating quickly untargeted metabolomics fingerprints. This study also
      describes the optimization of the parameters controlling the automatic processing
      in order to obtain a fast and reliable annotation of a maximum of organic
      compounds. This strategy was applied to bovine kidney samples collected from
      control animals or animals treated with steroid hormones. Thirty-eight compounds
      were identified successfully in the generated chemical phenotypes, among which
      five were found to be candidate markers of the administration of these anabolic
      agents, demonstrating the efficiency of the developed strategy to reveal and
      confirm metabolite structures according to the high-throughput objective expected
      from these integrative biological approaches.

PMID- 22970430
TI  - Surface-enhanced Raman scattering-active gold nanoparticles modified with a
      monolayer of silver film.
AB  - As shown in the literature, electrochemical underpotential deposition (UPD)
      offers the ability to deposit up to a monolayer of one metal onto a more noble
      metal with a flat surface. In this work, we develop an electrochemical pathway to
      prepare more surface-enhanced Raman scattering (SERS)-active substrates with Ag
      UPD-modified Au nanoparticles (NPs) by using sonoelectrochemical deposition
      dissolution cycles (SEDDCs). Encouragingly, the SERS of Rhodamine 6G (R6G)
      adsorbed on these Ag UPD-modified Au NPs exhibits a higher intensity by ca. 12
      fold magnitude, as compared with that of R6G adsorbed on unmodified Au NPs. The
      prepared SERS-active substrate demonstrates a large Raman scattering enhancement
      for R6G with a detection limit of 2 * 10(-14) M and an enhancement factor of 5.0
      * 10(8). Also, the strategy proposed in this work to improve the SERS effects by
      using UPD Ag based on SEDDCs has an effect on the smaller probe molecules of 2,2'
      bipyridine (BPy).

PMID- 22970431
TI  - Sensitive spectrofluorometry of cellular prion protein based on the on-off
      interaction between fluorescent dye-labelled aptamers and multi-walled carbon
      nanotubes.
AB  - The very simple and general spectrofluorometry of cellular prion protein (PrP(C))
      is reported in this contribution based on the on-off noncovalent interaction of
      fluorescent dye-labelled PrP(C) DNA aptamers with multi-walled carbon nanotubes
      (MWCNTs). Due to the pi-pi stacking interaction between the DNA bases of the
      aptamer and the carbon nanotubes, the fluorescent dye and the MWCNTs are brought
      into close proximity, which leads to fluorescence quenching with a ratio of up to
      87%. However, further addition of PrP(C), which disturbs the pi-pi interaction
      owing to the strong and specific binding of the aptamer to PrP(C), driving the
      aptamer away from the surface of the MWCNTs, restored the quenched fluorescence.
      This recovered fluorescence intensity was found to be in linear proportion to the
      PrP(C) concentration in the range of 8.2 to 81.7 nM, which builds the basis of
      the spectrofluorometry of the cellular prion protein.

PMID- 22970432
TI  - Highly efficient SERS substrate for direct detection of explosive TNT using
      popcorn-shaped gold nanoparticle-functionalized SWCNT hybrid.
AB  - This paper reports for the first time the development of a large-scale SERS
      substrate from a popcorn-shaped gold nanoparticle-functionalized single walled
      carbon nanotubes hybrid thin film for the selective and highly sensitive
      detection of explosive TNT material at a 100 femtomolar (fM) level.

PMID- 22970433
TI  - Can we safely state that laparoscopic Roux-en-Y Gastric bypass is a better weight
      loss procedure than adjustable band gastroplasty?

PMID- 22970434
TI  - Unilateral adrenal metastasis from non-small-cell lung cancer demonstrating very
      high FDG uptake with a standardized uptake value in excess of sixty.
AB  - We report the case of a 52-year-old man who presented with a 2-week history of
      dyspnea and wheeze. CT scan of the chest showed a large soft-tissue lesion in the
      right main bronchus extending into the trachea. Pathologic examination of
      endoscopic tracheal biopsies showed features consistent with a non-small-cell
      lung carcinoma. 18F-FDG PET/CT showed very high uptake of FDG in the bronchial
      tumor (high standardized uptake values: 25.1) and unexpected very intense uptake
      in the left adrenal gland (high standardized uptake values: 62.5). Laparoscopic
      adrenalectomy was performed, and subsequent histopathological examination
      confirmed metastatic non-small-cell carcinoma in the adrenal gland. Although
      adrenal malignancies are generally metabolically active, such high uptake of FDG
      within a metastatic lesion has not been reported previously.

PMID- 22970435
TI  - Retraction. Effects of exposure to a mobile phone on  testicular function and
      structure in adult rabbit.

PMID- 22970436
TI  - Large-scale STI services in Avahan improve  utilization and treatment seeking
      behaviour  amongst high-risk groups in India: an analysis of  clinical records
      from six states.
AB  - BACKGROUND: Avahan, the India AIDS Initiative, implemented a large HIV prevention
      programme across six high HIV prevalence states amongst high risk groups
      consisting of female sex workers, high risk men who have sex with men,
      transgenders and injecting drug users in India. Utilization of the clinical
      services, health seeking behaviour and trends in syndromic diagnosis of sexually
      transmitted infections amongst these populations were measured using the
      individual tracking data. METHODS: The Avahan clinical monitoring system included
      individual tracking data pertaining to clinical services amongst high risk
      groups. All clinic visits were recorded in the routine clinical monitoring system
      using unique identification numbers at the NGO-level. Visits by individual clinic
      attendees were tracked from January 2005 to December 2009. An analysis examining
      the limited variables over time, stratified by risk group, was performed.
      RESULTS: A total of 431,434 individuals including 331,533 female sex workers,
      10,280 injecting drug users, 82,293 men who have sex with men, and 7,328
      transgenders visited the clinics with a total of 2,700,192 visits. Individuals
      made an average of 6.2 visits to the clinics during the study period. The number
      of visits per person increased annually from 1.2 in 2005 to 8.3 in 2009. The
      proportion of attendees visiting clinics more than four times a year increased
      from 4% in 2005 to 26% in 2009 (p<0.001). The proportion of STI syndromes
      diagnosed amongst female sex workers decreased from 39% in 2005 to 11% in 2009
      (p<0.001) while the proportion of STI syndromes diagnosed amongst high risk men
      who have sex with men decreased from 12% to 3 % (p<0.001). The proportion of
      attendees seeking regular STI check-ups increased from 12% to 48% (p<0.001). The
      proportion of high risk groups accessing clinics within two days of onset of STI
      related symptoms and acceptability of speculum and proctoscope examination
      increased significantly during the programme implementation period. CONCLUSIONS:
      The programme demonstrated that acceptable and accessible services with
      marginalised and often difficult-to-reach populations can be brought to a very
      large scale using standardized approaches. Utilization of these services can
      dramatically improve health seeking behaviour and reduce STI prevalence.

PMID- 22970438
TI  - Surgical outcomes beyond the individual.

PMID- 22970437
TI  - The aging brain: current concepts, intervention strategies and the role of Ginkgo
      biloba extract EGb 761. Introduction.

PMID- 22970439
TI  - Ventricular systolic reserve in asymptomatic children previously treated with low
      doses of anthracyclines: a longitudinal, prospective exercise echocardiography
      study.
AB  - BACKGROUND: The time course of mild cardiotoxicity induced by anthracycline
      remains unknown. The aim of this study was to evaluate the long-term evolution of
      decreased myocardial reserve in children previously treated with a cumulative
      dose of anthracycline up to 100 mg/m(2). PATIENTS AND METHODS: Twenty-seven
      asymptomatic cancer survival patients (25 with lymphoblastic leukemia), in
      continuous remission and off treatment for >12 months with no alterations in
      conventional echocardiograms were evaluated by exercise echocardiography at 37 +/
      15.4 months (T1) and 101 +/- 24 months (T2) after finishing treatment (ADRIA
      group). This group was compared with 25 healthy individuals (control group)
      similar to the ADRIA group with respect to age and body surface area (BSA). All
      individuals underwent treadmill exercise testing according to Bruce protocol.
      Echocardiograms were performed before and immediately after exercise. RESULTS:
      The groups were similar regarding cardiac structure and left ventricular (LV)
      systolic function at rest at T1 and T2. The growth of LV posterior wall thickness
      related to BSA was lower in the ADRIA group at T2. Post exercise, smaller LV
      ejection indexes and attenuated changes in the afterload in ADRIA group were
      observed at T1 and T2. CONCLUSION: The decreased systolic reserve induced by a
      low dose of anthracycline in asymptomatic children and adolescents remains
      unaffected over a 5-year period, suggesting that positive outcomes in chronic
      cardiotoxicity would be expected in patients with mild impairment after
      anthracycline treatment.

PMID- 22970440
TI  - Retraction. Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic
      children: a randomized self-controlled study.

PMID- 22970441
TI  - [An image of a mental health worker in the current care system].

PMID- 22970442
TI  - [Cerebral vascular pathology in hereditary dysplasia of the cennective tissue].

PMID- 22970443
TI  - [Schizophrenia: prenatal and postnatal risk factors].

PMID- 22970445
TI  - [Top cited papers in Russian psychiatry].

PMID- 22970444
TI  - [Ethical and legal responsibility fr diagnosis of the dementia syndrome].

PMID- 22970446
TI  - Leukemic phase of Burkitt lymphoma.

PMID- 22970447
TI  - [Hearing-enhancing surgery in the children; the current state-of-the-art. Part 1.
      Tympanoplasty and myringoplasty].
AB  - This review of the current Russian-language and foreign literature is centered on
      the problem of hearing-enhancing operations in the children. The detailed data on
      tympanoplasty and myringoplasty are presented in conjunction with the indications
      and contraindications for these surgical interventions. Selected stages of
      operations are described with special reference to complicated cases. The factors
      determining the postoperative prognosis are discussed. The opinions of foreign
      and domestic authors, including debatable ones, are considered.

PMID- 22970448
TI  - [Specific morphological and functional features of the mucous membrane in the
      upper respiratory tract and the middle ear and the methods for their study].
AB  - The currently available data on the peculiarities of the morphological structure
      of the mucous membrane in the middle ear cavities are presented in conjunction
      with information on the functional features of the upper respiratory tract and
      the middle ear. A comprehensive review of the modern methods for the study od the
      mucociliary activity of the mucous membrane of the upper respiratory tract is
      provided.

PMID- 22970450
TI  - Mark H. Johnson.

PMID- 22970449
TI  - Turkey's biodiversity at the crossroads.

PMID- 22970451
TI  - Glaukos((r)) trabecular stent used to treat steroid-induced glaucoma.
AB  - PURPOSE: This case report illustrates the efficacy of the Glaukos trabecular
      bypass (Glaukos i-stent, Glaukos Corporation, Laguna Hills, California, USA) used
      for intraocular pressure (IOP) control in a patient with glaucoma induced by the
      steroid treatment of post-laser-assisted in situ keratomileusis (LASIK) bilateral
      anterior uveitis. METHODS: A 35-year-old woman who had undergone LASIK 5 months
      previously presented with blurred vision in both eyes. Examination revealed
      bilateral anterior uveitis and diffuse lamellar keratitis (DLK) requiring steroid
      treatment. In response to treatment, inflammation improved but the patient had
      increased IOP that was difficult to control. The course of pressure elevation was
      more aggressive in the left eye despite the gradual discontinuation of steroids.
      We therefore decided to place 2 trabecular i-stents in the left eye. RESULTS:
      This solution achieved good pressure control with no associated complications
      after 1 year follow-up. CONCLUSIONS: This trabecular bypass seems a safe and
      effective therapeutic option for IOP control when there is a poor response to
      conventional treatment in this type of secondary glaucoma.

PMID- 22970452
TI  - World Trade Center Health Program; addition of certain types of cancer to the
      list of WTC-related health conditions. Final rule.
AB  - Title I of the James Zadroga 9/11 Health and Compensation Act of 2010 amended the
      Public Health Service Act (PHS Act) to establish the World Trade Center (WTC)
      Health Program. The WTC Health Program, which is administered by the Director of
      the National Institute for Occupational Safety and Health (NIOSH), within the
      Centers for Disease Control and Prevention (CDC), provides medical monitoring and
      treatment to eligible firefighters and related personnel, law enforcement
      officers, and rescue, recovery, and cleanup workers who responded to the
      September 11, 2001, terrorist attacks in New York City, at the Pentagon, and in
      Shanksville, Pennsylvania, and to eligible survivors of the New York City
      attacks. In accordance with WTC Health Program regulations, which establish
      procedures for adding a new condition to the list of covered health conditions,
      this final rule adds to the List of WTC-Related Health Conditions the types of
      cancer proposed for inclusion by the notice of proposed rulemaking.

PMID- 22970453
TI  - Rare disease detected by head ultrasound in an infant hospitalized  for vomiting
      and irritability.

PMID- 22970454
TI  - [Standard diagnostic and therapeutic approaches to chronic hepatitis C virus
      infection].

PMID- 22970455
TI  - AAE Position Statement. Use of microscopes and other magnification techniques.

PMID- 22970456
TI  - Perspectives from a 26-year teaching career: what's the future?

PMID- 22970457
TI  - [Picture in clinical hematology; Clostridium perfringens septicemia with
      intravascular hemolysis].

PMID- 22970458
TI  - Travel bag: five supplies to have on hand. Out and about this fall? Here's what
      to bring for safe travels, our medical experts suggest.

PMID- 22970459
TI  - Does Joint Juice help against arthritis?

PMID- 22970460
TI  - What to do when a loved one dies.

PMID- 22970461
TI  - When costlier care isn't better.

PMID- 22970462
TI  - Yawning, or not having enough to do.

PMID- 22970463
TI  - Sexually transmitted diseases: introduction.

PMID- 22970464
TI  - Sexually transmitted diseases in primary care.

PMID- 22970465
TI  - Interrupting transmission of HIV and other sexually transmitted infections in
      Rhode Island.

PMID- 22970466
TI  - Infectious syphilis: the return of the great imitator to Rhode Island.

PMID- 22970467
TI  - Recommendations for the diagnosis of Neisseria gonorrhoeae and Chlamydia
      trachomatis, including extra-genital sites.

PMID- 22970468
TI  - Human papillomavirus (HPV) and trichomonas: common, concerning, and challenging
      sexually transmitted infections.

PMID- 22970469
TI  - Testing and treatment after non-occupational exposures to STDs and HIV.
AB  - Sexual exposure to STDs including HIV and hepatitis is common. Sexual assault is
      also prevalent and should be screened for in a patient presenting for medical
      care after potential sexual exposure to STDs. Primary care providers should be
      familiar with current recommendations for STD prophylaxis and treatment after
      sexual exposure to STDs, and be aware that HIV postexposure prophylaxis is
      effective and available if indicated after sexual exposure to HIV. Providers
      should also be aware of the need for prompt referal for evaluation and medical
      care of the adult patient after a sexual assault.

PMID- 22970470
TI  - Maternal smoking and birth defects in Rhode Island.

PMID- 22970471
TI  - A slow growing non-calcified airway mass.

PMID- 22970472
TI  - Perspectives of women about external breast prostheses.
AB  - As many as 90% of women who have undergone mastectomy or lumpectomy for breast
      cancer surgery will choose to wear a breast prosthesis. To date, there has been
      little systematic exploration of experiences and preferences related to wearing
      external breast prostheses, especially with new products. For this qualitative
      descriptive study, 24 women were interviewed regarding their perspectives about
      the conventional breast prosthesis and 19 about their perspectives regarding a
      newly available custom-designed breast prosthesis. Women spoke about difficulties
      obtaining information regarding available breast prostheses options; the
      awkwardness of being measured and fitted for a prosthesis, especially with
      seemingly untrained staff; challenges in wearing an external prosthesis; and how
      a prosthesis can foster increased confidence, enhanced body image and self
      esteem, and a sense of normalcy. All recommended that women must make an
      individual decision about wearing a breast prosthesis and emphasized how
      important it is to have information about options early in the cancer journey.
      The study findings can guide oncology nurses in educating women about breast
      prostheses.

PMID- 22970473
TI  - Theory inspired practice for end-of-life cancer care: an exploration of the
      McGill Model of Nursing.
AB  - Nursing theories provide inspiration for practice by describing how to meet
      needs, enhance wellness, and respond to clients as whole persons. This paper
      discusses the McGill Model of Nursing with reference to how its ideas can support
      nursing practice for patients with cancer during the end-of-life phase. We
      suggest this model provides for a relational approach that is congruent with the
      philosophy of palliative care. The goal of this paper is to stimulate reflection
      amongst oncology nurses and nursing leaders. By comparing the value base of our
      practice against extant nursing theory, we may discover new opportunities for
      teaching and learning about what it means to be an end-of-life care nurse.

PMID- 22970474
TI  - Palliative sedation to alleviate existential suffering at end-of-life: insight
      into a controversial practice.
AB  - All terminally ill individuals should have access to palliative care that gives
      equal importance to all aspects of suffering. In spite of all the efforts made,
      some of these individuals will, unfortunately, be left with suffering described
      as "refractory". It would appear that palliative sedation then becomes an option.
      There is much controversy around this practice, especially when it is used to
      alleviate suffering of a more existential nature. This article aims first to
      define the practice of palliative sedation, second to explore the concept of
      existential suffering in palliative care and third to address the implications
      for nursing practice.

PMID- 22970475
TI  - Strategies to use with interpreters in the clinical setting.

PMID- 22970476
TI  - Making a difference is its own record.

PMID- 22970477
TI  - Broad perspective: better insight, better you.

PMID- 22970478
TI  - Alternative pathway to ophthalmic care: advanced nursing perspective.

PMID- 22970479
TI  - When to administer the NEI-VFQ post-cataract surgery: an evidence-based approach.

PMID- 22970480
TI  - The role of telemedicine in eye care.

PMID- 22970481
TI  - Documentation errors related to electronic health records.

PMID- 22970482
TI  - Color-enhanced tinted contact lenses in the visual rehabilitation of a mild
      traumatic brain injury patient.

PMID- 22970483
TI  - Glaucoma and the brain.

PMID- 22970484
TI  - Keeping our minds sharp as we age.

PMID- 22970485
TI  - The Messages Project: maintaining the child/parent bond during parental
      incarceration.

PMID- 22970486
TI  - Pediatric palliative care: beyond the end of life.
AB  - Palliative care is an emerging nursing specialty and is developing a dedicated
      spot in the field of pediatrics. As a specialty, palliative care focuses on
      quality of life and symptom management for patients who are living with chronic
      and life-threatening diseases. In pediatrics, advances in health care mean that
      many children are living longer with these conditions and could benefit from
      services that focus on quality of life and superior symptom management.
      Palliative care can be provided concurrently with curative therapies and is
      philosophically similar yet distinct from hospice services.

PMID- 22970487
TI  - Evaluation of a coping kit for children with challenging behaviors in a pediatric
      hospital.
AB  - This study attempted to answer the question, "Do nurses perceive coping kits to
      be effective at meeting the needs of hospitalized children with developmental
      disabilities who are at increased risk for challenging behaviors?" A cross
      sectional post-test survey study design was used, with a convenience sample of 24
      registered nurses at a Midwestern free-standing children's hospital. A coping kit
      with simple communication cards, social script book, and distraction items (toys)
      was developed to enhance communication and distract children with developmental
      disabilities (including autism spectrum disorder) undergoing procedures in the
      hospital. A modified version of Hudson's (2006) intervention effectiveness survey
      was used to measure the nurse's perception of the effectiveness of the coping
      kit. Nurses perceived the coping kits to be effective for decreasing their
      patient's anxiety, calming the child's behavior, and increasing cooperation
      during procedures. The nurse can develop a plan of care that includes a coping
      kit to help gain cooperation with the hospitalized child with challenging
      behaviors.

PMID- 22970488
TI  - Evaluating an intervention tool.

PMID- 22970490
TI  - Utilization of internet resources for adolescents coping with chronic conditions.

PMID- 22970489
TI  - Changes in infant disposable diaper weights at selected intervals post-wetting.
AB  - Pediatric acute care nurses questioned the practice of weighing disposable infant
      diapers immediately after voiding. This study asked the research question, "Does
      volume of saline, diaper configuration, and/or size of diaper statistically
      effect changes in diaper weights over time?" The method was an experimental,
      laboratory model. Pre-set volumes of saline were added to disposable diapers that
      were then left folded or unfolded. Each diaper was weighed immediately post
      wetting and re-weighed at hourly intervals for seven hours. Data were analyzed
      using a repeated measures analysis of variance (RMANOVA) with balanced data (F
      test). Diaper weight changes over time were statistically significant for all
      time points and for all volumes regardless of diaper size; however, the changes
      in weight were small and without clinical significance. It is appropriate to
      weigh diapers at the end of eight hours without risk of altering subsequent fluid
      management of patients in open-air, non-humidified environments. This practice
      has led to more efficient use of nurses' time with fewer interruptions for
      patients and families.

PMID- 22970492
TI  - The epidemiology of falls in hospitalized children.

PMID- 22970491
TI  - Strategies for encouraging patient/family member partnerships with the health
      care team.
AB  - The 5th International Conference of the Institute for Patient- and Family
      Centered Care (IPFCC), held in Washington, DC, from June 4-6, 2012, offered an
      opportunity for almost 1,000 conference participants to share and learn about
      exciting new patient- and family-centered initiatives occurring across the U.S.
      and in many other countries. One focus addressed by keynote and plenary speakers,
      as well as numerous conference sessions and poster presentations, was how nurses
      and other health care professionals can encourage patients and family members to
      become partners with their health care teams. Various presenters shared
      strategies ranging from initial approaches to acknowledging family members as
      part of the team and offering simple, non-threatening roles in care provision, to
      policies and approaches inviting increased participation in health care
      encounters, to higher level involvement in the care planning process, and to
      partnership roles extending beyond care of the individual child and family. A
      wealth of ideas can be implemented at various levels by individual nurses, units,
      and health care institutions.

PMID- 22970493
TI  - Encopresis: a medical and family approach.

PMID- 22970494
TI  - Legislature approves $16.6 million to expand healthy kids.

PMID- 22970495
TI  - Comments on state's botox statement.

PMID- 22970496
TI  - Another perspective on hospital dentistry referrals.

PMID- 22970497
TI  - The future of dentistry.

PMID- 22970498
TI  - Can an M.D. or D.O. legally practice dentistry?

PMID- 22970499
TI  - Long-term financial stability is a goal at the ADA.

PMID- 22970500
TI  - Checking for criminal records: what you need to know.

PMID- 22970501
TI  - Medicare and that magic moment: age 65.

PMID- 22970502
TI  - Quality measurement in your office.

PMID- 22970503
TI  - The critical importance of a business plan.

PMID- 22970504
TI  - Survey of Michigan dentists and radiation oncologists on oral care of patients
      undergoing head and neck radiation therapy.
AB  - BACKGROUND: Oral complications of radiation therapy for head and neck cancer
      (HNC) are associated with a significant decline in oral health-related quality of
      life (OHQOL). The dentist, working with the radiation oncologist and the rest of
      the health care team, plays an important role in the prevention and management of
      these complications, but patients do not always receive care consistent with
      current guidelines. This study investigated barriers to recommended care.
      HYPOTHESES: There is variability in knowledge and practice among dentists and
      radiation oncologists regarding the dental management of patients treated with
      head and neck radiotherapy (HNRT), and inadequate communication and collaboration
      between members of the patient's health care team contribute to inconsistencies
      in application of clinical care guidelines. There is on interest and need for
      continuing dental (CDE) and medical education (CME) on this topic.
      MATERIALS/METHODS: A questionnaire was developed to assess dentists' knowledge
      and practice of dental management of HNC patients and their interest in CDE on
      this topic. All members of the Michigan Dental Association (MDA) with email
      addresses were asked to complete the survey online, and a random sample of MDA
      members without email addresses was invited to complete a paper version of the
      same survey. All Michigan members of the American Society for Radiation Oncology
      (ASTRO) were invited to complete an online version of the survey modified for
      radiation oncologists. RESULTS: The response rate for dentists was 47.9% and
      radiation oncologists was 22.3%. Of the dentists who responded, 81% reported that
      a major barrier to providing dental treatment before radiotherapy was a lack of
      time between initial dental consultation and the start of radiation; inadequate
      communication between health care providers was blamed most frequently for this.
      Ten percent of the dentists and 25% of the radiation oncologists reported that
      they did not treat HNC patients because they lacked adequate training, and 55% of
      dental respondents said that they did not feel adequately trained in dental
      school to treat patients who have had head and neck radiation therapy. Most
      respondents (radiation oncologists 67%; dentists 72%) were interested in CDE and
      CME on this topic. CONCLUSIONS: These results suggest a need for CDE and CME for
      Michigan dentists and radiation oncologists on the oral management of HNC
      patients. Improved training and communication between health professionals could
      improve patient outcomes and more consistent application of clinical care
      guidelines.

PMID- 22970505
TI  - Straws do not cause dry sockets when third molars are extracted.
AB  - PURPOSE: To provide evidence in contrast to a widely held belief that the dry
      socket, i.e., Alveolar Osteitis (AO), is primarily a biological process and not a
      mechanical disruption or removal of the clot due to suction from utilizing a
      straw in the postoperative period. PATIENTS AND METHODS: Sixty randomly selected
      patients had all 4 third molars extracted. One half of the patients were given
      straws to use with all meals for 2 days after surgery. RESULTS: Two-hundred
      twenty teeth were extracted. No dry socket occurred in the maxilla, 17 occurred
      in the mandible; 8 or 15% who had used a straw and 9 or 15% who did not.
      CONCLUSION: There is no evidence that there is an increased incidence of dry
      sockets when using a straw in the first 2 days after third molars have been
      extracted.

PMID- 22970506
TI  - Access to care in Michigan: what's next?

PMID- 22970507
TI  - Managing your money: why you need a true financial planner.

PMID- 22970508
TI  - Home, safe home: 8 ways to make your space diabetes-friendly.

PMID- 22970509
TI  - Get a move on: tips for psyching up to exercise and keeping it fresh.

PMID- 22970510
TI  - A syndrome of their own: PCOS and its links to diabetes in women.

PMID- 22970511
TI  - Aging gracefully: Is it time to take a bigger role in your older loved one's
      care?

PMID- 22970512
TI  - Honey, I studied my genes: Michael Snyder's stint as a lab rat sent him down a
      path of diabetes discovery.

PMID- 22970513
TI  - Health care reform round 2: The Supreme Court largely upheld the law revamping
      health insurance. Now what?

PMID- 22970514
TI  - If you build it...How new technologies are approved for people with diabetes.

PMID- 22970516
TI  - Pantry pleasers.

PMID- 22970515
TI  - Sofia's choice: Caregiver Sofia Spentzas starts taking care of herself and her
      prediabetes.

PMID- 22970517
TI  - Recipe for health.

PMID- 22970518
TI  - Fair-weather fare: Tips for smart eating during outdoor events.

PMID- 22970520
TI  - Two final rules from CMS expected to reduce regulatory burden.

PMID- 22970519
TI  - Approved: Standards revisions addressing patient flow through the emergency
      department.

PMID- 22970521
TI  - Ensuring the safety and security of radioactive materials.

PMID- 22970522
TI  - Approved: Revisions to the emergency management exercise requirement for home
      care.

PMID- 22970523
TI  - Approved: Revised waived testing EP.

PMID- 22970524
TI  - Approved: New behavioral health care standards for prevention and wellness
      promotion services.

PMID- 22970525
TI  - [Between cider and cirrhosis].

PMID- 22970526
TI  - [Drug-induced magnesium deficiency].
AB  - A lot of drugs can induce hypomagnesemia as side effect. On the other hand,
      magnesium deficiency may be a risk factor for digitalis and drugs known to
      prolong the QT-interval and thus favour the development of torsades-de-pointes
      tachycardias. Controversely, the indication for most oral magnesium supplements
      in Germany is: proven magnesium deficiency if this is the cause for muscular
      troubles (neuromuscular disturbances, calf cramps). Due to this cutback magnesium
      attracts poor attention in clinical practice and the determination of serum
      magnesium concentrations is seldom ordered. Moreover, the lower level of the
      reference range for serum magnesium is often kept too low. As a consequence
      hypomagnesemia as side effect remains frequently undetected.

PMID- 22970527
TI  - [Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of
      alcohol].
AB  - From the biomedical point of view alcohol is a Janus-faced dietary component with
      a dose-dependent effect varying from cardiovascular protection to cytotoxicity.
      Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is
      quickly distributed throughout body water and is mostly eliminated through
      oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and
      further to acetate is primarily localized in the liver. In case of a low blood
      alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized
      by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per
      thousand) are increasingly oxidized by the microsomal ethanoloxidizing system
      (MEOS). Alcohol consumption induces several metabolic reactions as well as acute
      effects on the central nervous system. Chronic alcohol consumption to some extent
      irreparably damages nearly every organ with the liver being particularly
      concerned. There are three stages of alcohol-induced liver disease (fatty liver,
      alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from
      reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen
      species). An especially dreaded clinical complication of the alcohol-induced
      liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial
      and self-perpetuating process with the swelling of astrocytes being a crucial
      point. Swollen astrocytes induce several reactions such as oxidative/nitrosative
      stress, impaired signal transduction, protein modifications and a modified gene
      expression profile. The swelling of astrocytes and the change in neuronal
      activity are attributed to several neurotoxins, especially ammonia and aromatic
      amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are
      common. The status of folic acid, thiamine, pyridoxine and zinc is especially
      critical.

PMID- 22970528
TI  - Sauce for the gander.

PMID- 22970529
TI  - Physician's passion for books benefits youngest patients and families.

PMID- 22970530
TI  - Comparison of time to endoscopy and outcome between weekend/weekday hospital
      admissions in patients with upper GI hemorrhage.
AB  - OBJECTIVE: Recent findings suggest that time to endoscopy is prolonged in
      patients admitted on the weekend with upper gastrointestinal hemorrhage (UGIH),
      which may result in increased adverse outcomes. This study was designed to
      determine if these findings hold true for a community gastroenterology practice.
      METHODS: This retrospective study reviewed patients admitted to a community
      teaching hospital from January 1, 2008, through October 31, 2008 with the primary
      diagnosis of UGIH. UGIH was further defined as acute variceal hemorrhage (AVH) or
      non-variceal hemorrhage (NVUGIH). The primary groups were based on weekend vs
      weekday admission. Time to endoscopy, adverse outcomes, presenting symptom, and
      length of stay were analyzed. RESULTS: One hundred seventy-four patients were
      included (50 weekend; 124 weekday). Most patients (94.25%) received upper
      endoscopy within 24 hours of admission. Mean time to endoscopy was shorter for
      weekend admission compared to weekday (7.52 hours vs 10.82 hours; P=0.012) for
      the entire group. No statistically significant difference was detected in AVH
      patients (6.37 hours vs 4.37 hours; P=0.09), but a difference was observed in the
      NVUGIH group (7.65 hours vs 11.45 hours, P=0.015). Adverse outcomes were not
      associated with weekend admission (P=0.583). There was no difference in mean
      length of stay (3.08 days vs 3.85 days; P=0.131) or mean units of blood
      transfused (2.44 units vs 2.07 units, P=0.417) between admission groups.
      CONCLUSIONS: Patients admitted to this community teaching hospital with UGIH on
      the weekend did not experience delayed endoscopy, increased adverse outcomes, or
      longer length of stay compared to those admitted on a weekday. The previously
      reported "weekend effect" was not observed. In fact, patients admitted with
      NVUGIH on the weekend received upper endoscopy earlier than patients admitted
      during the week.

PMID- 22970531
TI  - Evaluating effects of statewide smoking regulations on smoking behaviors among
      participants in the Survey of the Health of Wisconsin.
AB  - BACKGROUND: Studies have shown that laws banning smoking in public places reduce
      exposure to secondhand smoke, but the impact of such laws on exposure to smoke
      outside the home and on household smoking policies has not been well documented.
      The goal of this study was to evaluate the effects of 2009 Wisconsin Act 12, a
      statewide smoke-free law enacted in July 2010, among participants in the Survey
      of the Health of Wisconsin (SHOW). METHODS: Smoking history and demographic
      information was gathered from 1341 survey participants from 2008 to 2010. Smoking
      behaviors of independent samples of participants surveyed before and after the
      legislation was enacted were compared. RESULTS: The smoking ban was associated
      with a reduction of participants reporting exposure to smoke outside the home
      (from 55% to 32%; P<0.0001) and at home (13% to 7%; P=0.002). The new legislation
      was associated with an increased percentage of participants with no-smoking
      policies in their households (from 74% to 80%; P=.04). The results were stronger
      among participants who were older, wealthier, and more educated. CONCLUSION:
      Smoke-free legislation appears to reduce secondhand smoke exposure and to
      increase no-smoking policies in households. Further research should be conducted
      to see if these effects are maintained.

PMID- 22970532
TI  - Hypocalcemic myopathy secondary to hypoparathyroidism.
AB  - Myopathy is a rare manifestation of idiopathic hypoparathyroidism. We report a 48
      year-old man with a 6-year history of muscle pain and elevated creatine kinase
      levels. Laboratory analysis revealed low serum calcium, inappropriately low
      normal parathyroid hormone, elevated phosphorus, and normal 25-hydroxy vitamin D
      levels. The patient was diagnosed with idiopathic hypoparathyroidism and treated
      with calcium and calcitriol. He demonstrated an excellent clinical response and
      creatine kinase values returned to normal. This case illustrates the subtle
      nature of hypoparathyroid myopathy and highlights the importance of measuring
      serum calcium in patients with unexplained myalgia and/or muscle weakness.

PMID- 22970533
TI  - Proposal for a state health technology assessment program.
AB  - Evidence suggests that a significant number of medical technologies are of little
      or no benefit to patients. Under current budgetary pressures, state health care
      programs cannot afford continued spending on unnecessary medical care without
      further cuts in enrollment. Limiting coverage of high-tech care only to
      indications supported by good clinical evidence would help save state health care
      dollars. However, there is currently no public process to formally evaluate new
      medical interventions in Wisconsin. In fact, new therapies often are introduced
      into clinical practice, and covered by state health insurance programs, even when
      there is weak or questionable evidence of clinical effectiveness. This article
      proposes the creation of a state Health Technology Assessment program in
      Wisconsin to systematically evaluate new tests or treatments, and to promote
      evidence-based coverage decisions. Such a program would help limit wasteful
      spending on unnecessary technologies, reinforce good clinical practice, and
      protect patients from the risks of interventions that have not been proven
      effective.

PMID- 22970534
TI  - Office-based nursing staff management of hypertension in primary care.
AB  - A family medicine practice in a large multi-specialty clinic undertook a quality
      improvement initiative focusing on blood pressure control. Current rooming
      procedures were reviewed, including obtaining accurate and reliable blood
      pressures. All rooming staff were instructed how to take an accurate blood
      pressure and were observed at random over a 3-month period to ensure continued
      accuracy. Rooming staff (medical assistants and licensed practical nurses) were
      engaged to give patient education and to arrange a standard 2-week follow-up with
      a rooming staff team member (nurse visit) if the patient's blood pressure was
      elevated. Clinicians were educated briefly about the importance of managing
      hypertension regardless of reason for visit. Blood pressure control (<140/90) in
      patients age 18-85 without diabetes improved from 68.4% to 75.8% in 3 months.

PMID- 22970535
TI  - Supreme Court upholds Affordable Care Act, questions remain.

PMID- 22970537
TI  - Pharmacy fast forward.

PMID- 22970536
TI  - The Wisconsin Partnership Program: investing in a healthier state.

PMID- 22970538
TI  - Mobility in nursing: An ongoing evolution. Why providers are investing
      strategically in nurse-friendly mobile solutions.

PMID- 22970539
TI  - Breaking through to the other side. How provider organizations are strategizing
      to break new ground in healthcare.

PMID- 22970540
TI  - After Supreme Court ruling, HIT leaders ready to move forward. Health leaders at
      the Association of Medical Directors of Information Systems' Physician Symposium
      comment on ACA ruling.

PMID- 22970541
TI  - Emphasizing the patient in a patient-centered medical home. A Michigan physician
      has used a patient portal to create a PCMH.

PMID- 22970542
TI  - No-cost EHR as population health platform. HIE, PHR complement hit offering to
      glean actionable health information.

PMID- 22970543
TI  - An alternative approach to 24/7 ICU coverage. Can tele-ICU monitoring fill the
      intensivist shortage?

PMID- 22970544
TI  - Secrets of private-sector ACO innovation. What Blue Shield of California's Juan
      Davila knows.

PMID- 22970545
TI  - A potential passport for care coordination. An online medical dashboard,
      currently in development, is aimed at creating a constant two-way communication
      platform for physicians and patients.

PMID- 22970546
TI  - Quality data warehouses mitigate reporting challenges. Beth Israel Deaconess,
      Adirondack patient-centered medical home project utilize QDC for reporting needs.

PMID- 22970547
TI  - Hiring managers' pet peeves. An inside look at common interviewing mistakes that
      sink a candidate's chances for being hired.

PMID- 22970548
TI  - Our independence day: a summertime reflection.

PMID- 22970549
TI  - Nursing is the room rate.
AB  - Shrinking dollars increase the need for health care stakeholders to clearly
      understand nursing's worth. For nursing to assure an adequate investment in
      nurses, it needs to articulate its value drivers. Nursing revenue offers a data
      source that reflects stakeholder choices and patient needs. The daily nursing
      billing supports hospital payment and provides cost data, important for hospital
      financial decision making. This revenue is a tangible asset reflecting nursing
      value and can be used to justify an investment in the profession. Nursing
      leadership can use this daily nursing charge data to monitor and measure the
      impact of efficiencies related to patient care.

PMID- 22970550
TI  - The importance of employment status in determining exit rates from nursing.
AB  - To mitigate nurse shortages, health care decision makers tend to employ retention
      strategies that assume nurses employed in full-time, part-time, or casual
      positions and working in different sectors have similar preferences for work.
      However, this assumption has not been validated in the literature. The
      relationship between a nurse's propensity to exit the nurse profession in Ontario
      and employment status was explored by building an extended Cox Proportional
      Hazards Regression Model using a counting process technique. The differential
      exit patterns between part-time and casual nurses suggest that the common
      practice of treating part-time and casual nurses as equivalent is misleading.
      Health care decision makers should consider nurse retention strategies
      specifically targeting casual nurses because this segment of the profession is at
      the greatest risk of leaving. Nurse executives and nurse managers should
      investigate the different work preferences of part-time and casual nurses to
      devise tailored rather than "one-size fits all" nurse retention strategies to
      retain casual nurses.

PMID- 22970551
TI  - New graduate nurse residency program: a cost-benefit analysis based on turnover
      and contract labor usage.
AB  - A cost-benefit analysis was conducted to assess the economic outcomes of a new
      graduate registered nurse (NGRN) residency program utilizing turnover rate and
      contract labor usage data from a multi-site health care corporation. Secondary
      data analysis of NGRNs (n=524) was conducted including descriptive and step-wise
      regression analyses. Findings indicated a new graduate residency program was
      associated with a decrease in the 12-month turnover rate from 36.08% to 6.41%
      (p<0.05) and reduction in contract labor usage from $19,099 to $5,490 per average
      daily census (p<0.05). These cost-benefit analyses suggest net savings between
      $10 and $50 per patient day when compared to traditional methods of orientation.
      A NGRN residency program offers a cost-effective innovative approach and should
      be valued as an investment as opposed to an expense.

PMID- 22970552
TI  - Transition programs for internationally educated nurses: what can the United
      States learn from the United Kingdom, Australia, and Canada?
AB  - It is critical to conduct competency assessments of internationally educated
      nurses (IENs) to ensure public safety, as well as uphold accountability to
      nursing as a regulated profession. Transition programs are needed because of the
      required proficiency of the working language, as well as differences in nursing
      education, national health care systems, nursing practice and culture, etc.
      Transition programs in the United States are grossly under-developed because of
      lack of recognition of their importance, lack of funding and standardization, and
      decentralized regulation in nursing. United States can learn from the United
      Kingdom, Australia, and Canada regarding how to best transition IENs. Its current
      hit-and-miss approach is inadequate and inconsistent with the emerging global
      trend to systematically deal with the transitional challenges of IENs at the
      national level.

PMID- 22970553
TI  - Quality in life and death: can we have the conversations?
AB  - As nurses, we participate in providing social justice through the delivery of
      health care. While much of what we do supports healthier lifestyles and healing,
      we must also acknowledge that for an increasing number of our patients, life may
      have become irreversibly painful and unwanted. Nurses have acute sensitivity to
      the dilemmas faced by dying patients and their families. Our empathy and know-how
      in such cases dictates that we make an effort to relieve such suffering. Easing
      suffering will require assessments of the changing terrain of end-of-life care
      and the populations receiving that care. Dialogues can bridge the interest of
      patients, providers, and policymakers and ultimately legislation that reinforces
      ethical end-of-life care and ensures a voice for those who will be most affected.

PMID- 22970554
TI  - Navajo nation public health nurses inspire thoughts on health care reform.
AB  - The wisdom and experience of pubic health nurses serving on a Navajo Reservation,
      who work far from the typical hospital setting, may well hold some of the keys to
      how we can successfully plan for and navigate the future of our shifting health
      care system. As more of the nursing workforce moves outside the walls of the
      hospital, competencies in autonomy, clinical judgment, decision making, and
      communication will increase in importance. long with safety and quality
      implications, this may also influence changes in nursing education, job
      requirements, hiring, and measuring performance. In addition, there may be
      implications around how new nurses are oriented and how they get the experience
      needed to function in more independent roles. Within their routine days, the
      conditions they work in, the situations they face, and the many ways public
      health nurses find to meet the needs of the people they serve, is a wealth of
      knowledge that may well translate into solutions for some of the challenges our
      nation's health care system is facing.

PMID- 22970555
TI  - An online portal to support the role of the nurse manager.
AB  - To encourage retention in nursing administration while building leadership
      capacity, efforts must be made to support the manager's practice and professional
      development. Functions and duties of the nurse manager need to be simplified and
      supplemental development materials need to be readily available. Innovations that
      organize necessary document templates and ease access to materials that enhance
      their leadership skills have real value. One institution's innovation to build
      nurse manager capacity was an online portal for nurse managers. The site offers
      information that enriches the role of nurse manager and represents one
      supplemental pathway to continuous leadership development.

PMID- 22970557
TI  - Nutrient signaling: evolutionary origins of the immune-modulating effects of
      dietary fat.
AB  - Many dietary fatty acids (FA) have potent effects on inflammation, which is not
      only energetically costly, but also contributes to a range of chronic diseases.
      This presents an evolutionary paradox: Why should the host initiate a costly and
      damaging response to commonly encountered nutrients? We propose that the immune
      system has evolved a capacity to modify expenditure on inflammation to compensate
      for the effects of dietary FA on gut microorganisms. In a comprehensive
      literature review, we show that the body preferentially upregulates inflammation
      in response to saturated FA that promote harmful microbes. In contrast, the host
      opften reduces inflammation in response to the many unsaturated FA with
      antimicrobial properties. Our model is supported by contrasts involving shorter
      chain FA and omega-3 FA, but with less consistent evidence for trans fats, which
      are a recent addition to the human diet. Our findings support the idea that the
      vertebrate immune system has evolved a capacity to detect diet-driven shipfts in
      the composition of gut microbiota from the profile of FA consumed and to
      calibrate the costs of inflammation in response to these cues. We conclude by
      extending the nutrient signaling model to other nutrients, and consider
      implications for drug discovery and public health.

PMID- 22970556
TI  - American Academy of Ambulatory Care Nursing position statement: The role of the
      registered nurse in ambulatory care.

PMID- 22970558
TI  - Sherlock Holmes and intelligent design.
AB  - This article examines how both scientists and creationists, as they argue over
      intelligent design, invoke and quote the fictional character of Sherlock Holmes
      to support their opposed positions. Rhetorical analysis ofHolmes's repeated
      contributions to the debate reveals not only how the argument for design falls
      apart, but also how the argument for Darwin compromises itself when following the
      detective onto shaky logical ground. The sciences and the humanities must work
      together to combat the corrosive influence ofpseudoscientific reasoning on our
      students and the general public; this article contributes to that joint
      enterprise.

PMID- 22970560
TI  - Determination of myo-inositol (free and bound as phosphatidylinositol) in infant
      formula and adult nutritionals by liquid chromatography/pulsed amperometry with
      column switching: first action 2011.18.
AB  - Myo-inositol is a 6-carbon cyclic polyalcohol also known as meso-inositol, meat
      sugar, inosite, and i-inositol. It occurs in nature in both free (myo-inositol)
      and bound (inositol phosphates and phosphatidylinositol) forms. For the
      determination of free myo-inositol, samples are mixed with dilute hydrochloric
      acid to extract myo-inositol and precipitate proteins, diluted with water, and
      filtered. For the determination of myo-inositol bound as phosphatidylinositol,
      samples are extracted with chloroform, isolated from other fats with silica SPE
      cartridges, and hydrolyzed with concentrated acid to free myo-inositol. Prepared
      samples are first injected onto a Dionex CarboPac PA1 column, which separates myo
      inositol from other late-eluting carbohydrates. After column switching, myo
      inositol is further separated on a CarboPac MA1 column using a 0.12% sodium
      hydroxide mobile phase; strongly retained carbohydrates are eluted from the PA1
      column with a 3% sodium hydroxide mobile phase. Eluant from the CarboPac MA1
      analytical column passes through an electrochemical detector cell where myo
      inositol is detected by pulsed amperometry using a gold electrode. The method
      showed appropriate performance characteristics versus selected established
      standard method performance requirement parameters for the determination of myo
      inositol: linear response; repeatability (RSDr) of 2%; and intermediate precision
      (RSDir) of 2.5%. Instrument LOD and LOQ were 0.0004 and 0.0013 mg/100 mL,
      respectively, and correspond to a free myo-inositol quantitation limit of 0.026
      mg/100 g and a phosphatidylinositol quantitation limit of 0.016 mg/100 g.
      Correlation with the reference microbiological assay was good. The proposed
      method has been accepted by the Expert Review Panel as an AOAC First Action
      Method, suitable for the routine determination of myo-inositol in infant formula
      and adult nutritionals.

PMID- 22970559
TI  - Determination of vitamin B12 in infant formula and adult nutritionals using HPLC
      after purification on an immunoaffinity column: first action 2011.09.
AB  - During the "Standards Development and International Harmonization: AOAC
      INTERNATIONAL Mid-Year Meeting," on June 29, 2011, the method "Determination of
      vitamin B12 in infant formula and adult nutritionals using HPLC after
      purification on an immunoaffinity column" was recommended by an Expert Review
      Panel and adopted as AOAC Official First Action status. The method is applicable
      for the determination of vitamin B12 in milk-based infant formula. Vitamin B12 is
      extracted from the sample in sodium acetate buffer in the presence of potassium
      cyanide. After purification and concentration with an immunoaffinity column
      (IAC), vitamin B12 is determined by LC with UV detection (361 nm). Data supplied
      by CLF demonstrated linear response over a wide range of concentrations (1.4-39
      microg/100 mL). The analytical range is 0.2-10 microg/100 g, depending on the
      capacity of the IACs (0.01-0.5 microg), the input weight, and dilutions. Recovery
      rates were assessed using National Institute of Standards and Technology SRM
      1849, and determined to be 95.1%, with SD of 0.34 and CV of 9.0. Measurement
      uncertainty (UE) was 0.8 microg/100 g, which was calculated from the validation
      data. It is an expanded measurement uncertainty and was obtained through
      multiplication with a coverage factor k. LOQ values were reported as 0.10
      microg/100 g. The performance characteristics of the method met the standard
      method performance requirements set forth by the AOAC Stakeholder Panel on Infant
      Formula and Adult Nutritionals; thus, the method was determined to be appropriate
      for First Action status.

PMID- 22970561
TI  - ERP grants first action status to candidate tissue residue methods for high
      priority animal drugs.

PMID- 22970562
TI  - Determination of ractopamine in swine, bovine, and turkey tissues by HPLC with
      fluorescence detection: first action 2011.22.
AB  - A candidate LC method proposed by the Expert Review Panel (ERP) for ractopamine
      was evaluated in a single-laboratory validation (SLV) study. The matrixes
      examined included bovine liver, kidney, muscle, and fat; swine liver, kidney,
      muscle, and fat; and turkey liver and muscle. Solution standards were shown to
      provide a linear response with an unweighted regression. The method demonstrated
      acceptable precision (HorRat, values 0.25 to 1.38) and recovery (75.4 to 88.8%)
      in all fortified matrixes. Method precision was verified with incurred residue
      tissues (bovine liver, kidney, and muscle; swine liver, kidney, and muscle; and
      turkey liver and muscle), which yielded RSDr values below 16% for all tissues and
      below 7% for most tissues. Estimated LOQ values ranged from 1.8 to 20.7 ng/g and
      support the utility of the method in the range of the maximum residue limits or
      tolerances for the various tissues. The data satisfy the requirements of the AOAC
      Stakeholder Panel on Veterinary Drug Residue for SLV studies, and the method was
      adopted Official Methods ofAnalysis First Action 2011.22 by the AOAC ERP on
      Veterinary Drug Residues.

PMID- 22970563
TI  - Determination of narasin and monensin in bovine, swine, and chicken tissues by
      liquid chromatography with tandem mass spectrometry: first action 2011.24.
AB  - The single-laboratory validation (SLV) of an LC-MS/MS method for determination
      and confirmation of two ionophores, narasin and monensin, in animal tissues is
      described. The data demonstrated linearity of matrix-matched calibration curves
      using a weighted (1/x) regression and selectivity of the method for narasin and
      monensin in the presence of lasalocid, salinomycin, maduramycin, nicarbazin, and
      sulfadiazine. Recoveries varied from 86.2 to 103.5% for narasin and 89.1 to
      105.1% for monensin. Intertrial repeatability precision [relative standard
      deviation of repeatability (RSDr)] varied from 3.9 to 13.8% for narasin and 3.3
      to 16.3% for monensin in fortified tissue. Precision of the method was verified
      in incurred tissues. The LOQ of the method was validated and ranged from 0.45
      ng/g in milk, to 4.0 ng/g in chicken fat, but was 0.75 ng/g for most tissues. Two
      confirmatory ions for each analyte were examined across all matrixes, resulting
      in estimated false-negative rates of 0.00% (95% confidence interval of 0.00
      0.68%) for monensin ions (540 samples) compared to the U.S. and European Union
      (EU) acceptance criteria. The confirmatory ions for narasin demonstrated 0.00%
      false-negative rates (95% confidence interval of 0.00-0.58%) when compared to
      either the U.S. or EU criteria in 630 samples. The method was robust when small
      changes in method parameters were made and stability of fortified tissues,
      extracts, and calibration solutions were estimated. The data satisfy the
      requirements of the AOAC Stakeholder Panel on Veterinary Drug Residue for SLV
      studies, and the method was adopted Official Methods of Analysis First Action
      2011.24 by the AOAC Expert Review Panel on Veterinary Drug Residues.

PMID- 22970564
TI  - Biennial review of planar chromatography: 2009-2011.
AB  - The most important advances in the planar chromatography published between
      November 1, 2009 and November 1, 2011 are reviewed in this paper. Included are an
      introduction to the current status of the field; history, student experiments,
      books, and reviews; theory and fundamental studies; apparatus and techniques for
      sample preparation and TLC separations (sample application and plate development
      with the mobile phase); detection and identification of separated zones (chemical
      and biological detection, TLC/MS, and TLC coupled with other methods); techniques
      and instruments for quantitative analysis; preparative layer chromatography; and
      thin layer radiochromatography. Selected applications are given in the various
      sections of the review, especially for modern HPTLC-densitometry.

PMID- 22970565
TI  - Development and validation of a liquid chromatographic/ tandem mass spectrometric
      method for determination of chlortetracycline, oxytetracycline, tetracycline, and
      doxycycline in animal feeds.
AB  - A selective and accurate LC/MS/MS method for the simultaneous determination of
      chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC), and
      doxycycline (DC) in animal feeds was developed. Samples were extracted with
      Na2EDTA-McIlvaine buffer and further purified with Oasis HLB SPE columns. The
      purified extract was separated on an Xbridge C18 column and detected by LC/MS/MS
      with positive electrospray ionization in the multiple reaction monitoring mode.
      This method provided average recoveries of 80.9 to 119.5%, with CVs of 1.7 to
      9.8% in the range of 0.5 to 50 mg/kg CTC, OTC, TC, and DC in feeds, except the
      average recovery of CTC was 76.0%, with a CV of 14.6% in pig feed spiked with 0.5
      mg/kg CTC. The linear ranges for the four TCs determined by LC/MS/MS ranged from
      0.005 to 2.5 microg/mL with a linear correlation coefficient (R2) >0.99. The LOD
      and LOQ for CTC, OTC, TC, and DC in pig and poultry feeds ranged from 0.003 to
      0.02 and 0.01 to 0.05 microg/g, respectively. The method was successfully applied
      for the analysis of 30 real feed samples, and no illegal use was detected.

PMID- 22970566
TI  - Rapid method for the simultaneous determination of six ionophores in feed by
      liquid chromatography/mass spectrometry.
AB  - A simple and highly sensitive LC/MS method was developed for the simultaneous
      determination of six ionophores--lasalocid, monensin, laidlomycin, maduramycin,
      salinomycin, and narasin--in feed. The procedure involved extraction of 1 g of
      feed with 4 mL of methanol-water (9 + 1, v/v) by shaking on a platform shaker for
      45 min. After centrifugation, the extracts were diluted with methanol-water (75 +
      25, v/v) and analyzed without any cleanup. The analysis was performed on a
      Betasil C18 column (150 x 4.6 mm id, 5 pm particle size) connected to an LC/MS
      system operated in the atmospheric pressure chemical ionization (APCI) mode. We
      believe this to be the first method that uses the APCI mode for the analysis of
      ionophores. The mobile phase consisted of 50 mM ammonium acetate as solvent A and
      acetonitrile-methanol (7 + 3, v/v) as solvent B in a gradient run. Excellent
      recoveries of 81-120% were found for all compounds at fortification levels of 1
      200 microg/g, with RSD < or =15% (except 17% for maduramycin at 2 and 5 microg/g,
      and 16% for salinomycin at 1 microg/g). At 0.5 microg/g, recoveries of 87-119%
      were obtained, with RSD < or =20%. However, recovery of lasalocid was 133% and
      salinomycin 79% in sow and horse feed, respectively. Average RSD values of
      lasalocid and salinomycin were 22 and 21%, respectively. Finally, proficiency
      test samples analyzed with the method demonstrated favorable agreement with the
      certified values.

PMID- 22970567
TI  - DNA barcode identification of black cohosh herbal dietary supplements.
AB  - Black cohosh (Actaea racemosa) herbal dietary supplements are commonly consumed
      to treat menopausal symptoms, but there are reports of adverse events and
      toxicities associated with their use. Accidental misidentification and/or
      deliberate adulteration results in harvesting other related species that are then
      marketed as black cohosh. Some of these species are known to be toxic to humans.
      We have identified two matK nucleotides that consistently distinguish black
      cohosh from related species. Using these nucleotides, an assay was able to
      correctly identify all of the black cohosh samples in the validation set. None of
      the other Actaea species in the validation set were falsely identified as black
      cohosh. Of 36 dietary supplements sequenced, 27 (75%) had a sequence that exactly
      matched black cohosh. The remaining nine samples (25%) had a sequence identical
      to that of three Asian Actaea species (A. cimicifuga, A. dahurica, and A.
      simplex). Manufacturers should routinely test plant material using a reliable
      assay to ensure accurate labeling.

PMID- 22970568
TI  - Reflectance near-infrared spectroscopic method with Chemometric techniques for
      simultaneous determination of Chondroitin, glucosamine, and methyl sulfonyl
      methane.
AB  - Reflectance near-IR (RNIR) spectroscopy was used for the simultaneous
      determination of chondroitin (CH), glucosamine (GO), and methyl sulfonyl methane
      (MSM) in tablets. Simple sample preparation was done by grinding, sieving, and
      compression of the tablets for improving RNIR spectra. Principal component
      regression and partial least squares (PLS-1 and PLS-2) were successfully applied
      to quantify the three components in the studied mixture using information
      included in RNIR spectra in the range of 4350-9100 cm(-1). The calibration model
      was developed with drug concentration ranges of 14.5-44.2% (w/w) for CH, 18.4
      55.3% (w/w) for GO, and 6-18.6% (w/w) for MSM with addition of tablet excipients
      to the calibration set in the same ratio as in the tested tablets. The
      calibration models were evaluated by internal validation, cross-validation, and
      external validation using synthetic and pharmaceutical preparations. The proposed
      method was applied for analysis of six batches of the pharmaceutical product. The
      results of the proposed method were compared with the results of the
      pharmacopoeial method for the same batch of the pharmaceutical product. No
      significant differences between the results were found. The RNIR method is
      accurate and precise, and can be used for QC of pharmaceutical products.

PMID- 22970569
TI  - High-performance liquid chromatography quantification of principal antioxidants
      in black seed (Nigella sativa L.) phytopharmaceuticals.
AB  - A new, simple, sensitive, rapid, and accurate isocratic RP-HPLC method was
      developed and validated for simultaneous analysis of the principal antioxidants
      of Nigella sativa, i.e., thymoquinone (TQ), carvacrol (CR), and its isomer thymol
      (THY), in different phytopharmaceuticals. The mobile phase was water-methanol (40
      + 60, v/v) at a flow rate of 1.5 mL/min. Quantification was achieved with UV
      detection at 254 nm, based on peak area. The method was validated for linearity,
      accuracy, precision, selectivity, and robustness. The proposed method is
      stability-indicating for determination of TQ in the presence of its degradants.
      The LOD and LOQ (microg/mL) were, respectively, 0.006 and 0.021 for TQ, 0.002 and
      0.006 for CR, and 0.027 and 0.090 for THY. The mean recoveries measured at three
      concentrations were higher than 99%, with RSD <2%. This analytical method is
      suitable for quality control of the marker substances in this widely used natural
      protective and curative remedy.

PMID- 22970570
TI  - Structure elucidation of a novel analog of sildenafil detected as an adulterant
      in a dietary supplement using LC-UV and LC/MS.
AB  - A sildenafil-related compound was detected in a dietary supplement marketed as an
      aphrodisiac. The compound was detected during analysis of the dietary supplement
      using LC-UV and LC/electrospray ionization-MS. The structure of the compound was
      established using high resolution MS, NMR spectrometry, and X-ray crystal
      structure analysis. The compound was identified as 5-(5-((3,5-dimethylpiperazin-1
      yl)sulfonyl)-2-ethoxyphenyl)-l-methyl-7-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)
      3-propyl-1H-pyrazolo[4,3-d] pyrimidine. Based on this structure, the compound was
      named nitroprodenafil. The dietary supplement was found to contain 90 mg
      nitroprodenafil/capsule. This article describes the structural characterization
      of a new sildenafil-related compound. The compound was detected during analysis
      of a dietary supplement using LC-UV and LC/electrospray ionization (ESI)-MS. The
      structure was established using high resolution MS (HRMS), NMR spectrometry, and
      X-ray crystal structure analysis. The structures of methisosildenafil,
      thiomethisosildenafil, and this new analog, named nitroprodenafil (21), are shown
      in Figure 1. In the Demizu et al. report, the compound is named mutaprodenafil
      instead ofnitroprodenafil. Considering the naming right, the authors of this
      paper think the use of mutaprodenafil is appropriate as the compound name,
      although nitroprodenafil is used.

PMID- 22970571
TI  - Quality assessment of Fructus xanthii based on fingerprinting using high
      performance liquid chromatography.
AB  - Because almost every traditional Chinese medicine (TCM) is a multicomponent
      system, QC of TCMs always involves various difficulties. As a current popular
      quality assessment approach, focusing on qualitative and quantitative analysis of
      certain compounds contained in herbal medicine has been widely used for the sake
      of expediency rather than being a practical and realistic way. However, this
      method does not take the existence of other constituents into account.
      Comparatively, the chromatographic fingerprint of the components is a more
      suitable approach to holistically assess the quality of herbal drugs. Fructus
      xanthii is a well-known herbal drug listed in all editions of the Chinese
      Pharmacopoeia. However, there is no quality evaluation method given in its
      monograph, even for the above-mentioned expediency. This paper reports an HPLC
      fingerprinting method for quality evaluation of F. xanthii. The HPLC profiles of
      27 batches of commercial samples were further analyzed using chemometric methods,
      including similarity evaluation and principal component analysis. As a result,
      the established HPLC fingerprint contained 23 characteristic peaks; therein, 13
      peaks were unambiguously assigned by comparing their retention times and UV
      spectra with those of reference compounds, and five peaks were tentatively
      identified on the basis of their MS/MS fragmentation patterns and UV spectra.
      Moreover, it could be clearly observed that caffeoylquinic acid and its analogs
      predominate in F. xanthii. Except for three samples identified as outliers, 24
      other commercial samples displayed similar HPLC profiles, indicating that the
      quality of the herbs from different markets is stable and consistent.

PMID- 22970572
TI  - Procedural revision to the use-dilution methods: establishment of maximum log
      density value for test microbes on inoculated carriers.
AB  - (Staphylococcus aureus) and 964.02 (Pseudomonas aeruginosa), were revised in 2009
      to include a standardized procedure to measure the log density of the test
      microbe and to establish a minimum mean log density value of 6.0 (geometric mean
      of 1.0 x 10(6) CFU/carrier) to qualify the test results. This report proposes
      setting a maximum mean log density value of 7.0 (geometric mean of 1.0 x 10(7)
      CFU/carrier) to further standardize the procedure. The minimum value was based on
      carrier count data collected by four laboratories over an 8-year period (1999
      2006). The data have been updated to include an additional 4 years' worth of data
      (2006-2010) collected by the same laboratories. A total of 512 tests were
      conducted on products bearing claims against P. aeruginosa and S. aureus with and
      without an organic soil load (OSL) added to the inoculum (as specified on the
      product label claim). Six carriers were assayed in each test, for a total of 3072
      carriers. Mean log densities for each of the 512 tests were at least 6.0. With
      the exception of two tests, one for P. aeruginosa without OSL and one for S.
      aureus with OSL, the mean log densities did not exceed 7.5 (geometric mean of 3.2
      x 10(7) CFU/carrier). Across microbes and OSL treatments, the mean log density
      (+/- SEM) was 6.80 (+/- 0.07) per carrier (a geometric mean of 6.32 x 10(6)
      CFUlcarrier) and acceptable repeatability (0.28) and reproducibility (0.31) SDs
      were exhibited. A maximum mean log density per carrier of 7.0 is being proposed
      here as a validity requirement for S. aureus and P. aeruginosa. A modification to
      the method to allow for dilution of the final test cultures to achieve carrier
      counts within 6.0-7.0 logs is also being proposed. Establishing a range of 6.0
      7.0 logs will help improve the reliability of the method and should allow for
      more consistent results within and among laboratories.

PMID- 22970573
TI  - Quantitation of transdermal tadalafil in human skin by reversed-phase high
      performance liquid chromatography.
AB  - A reliable and sensitive HPLC method was developed for the quantitation of
      tadalafil transdermal permeation through human skin. An RP column with UV
      detection at 290 nm was used for chromatographic separation at ambient
      temperature. The mobile phase was acetonitrile-water containing 20 mM pH 7
      phosphate buffer (35/65, v/v) with a flow rate of 1.0 mL/min. The LOQ achieved
      was 1 ng/mL, and the calibration curve showed good linearity over the
      concentration range of 5-2000 ng/mL for tadalafil, with a determination
      coefficient (R2) of 0.998. The RSD values of intraday and interday analyses were
      all within 7%. Parameters of validation proved the precision of the method; this
      validated method was applied for the determination of tadalafil in transdermal
      permeation and drug deposition in human skin studies.

PMID- 22970574
TI  - Simultaneous determination of eleven preservatives in cosmetics by micellar
      electrokinetic chromatography.
AB  - A new method for the simultaneous quantitation of 11 preservatives-imidazolidinyl
      urea, benzyl alcohol, dehydroacetic acid, sorbic acid, phenoxyethanol, benzoic
      acid, salicylic acid, and four parabens (methyl, ethyl, propyl, and butyl)-in
      cosmetics by micellar electrokinetic capillary chromatography was established and
      validated. The separation was performed using an uncoated fused-silica capillary
      (50 pm id x 60.2 cm, effective length 50 cm) with a running buffer consisting of
      15 mmol/L sodium tetraborate, 60 mmol/L boric acid, and 100 mmol/L sodium dodecyl
      sulfate. A 1:10 dilution of the running buffer was used as the sample buffer to
      extract the cosmetic samples. The key factors, such as the concentration and pH
      of the running and sample buffers, which influence quantitative analysis of the
      above 11 preservatives in cosmetic samples, were investigated in detail. The
      linear ranges of the calibration curves for imidazolidinyl urea and the other 10
      preservatives were 50-1000 and 10-200 mg/L, respectively. The correlation
      coefficients of the standard curves were all higher than 0.999. The recoveries at
      the concentrations studied ranged from 93.0 to 102.7%. RSDs were all less than
      5%. The new method with simple sample pretreatment met the needs for routine
      analysis of the 11 preservatives in cosmetics.

PMID- 22970575
TI  - Evaluation of applied biosystems MicroSEQ real-time PCR system for detection of
      Listeria spp. in food and environmental samples.
AB  - A complete system for real-time PCR detection of Listeria species was validated
      in five food matrixes and five environmental surfaces, namely, hot dogs, roast
      beef, lox (smoked salmon), pasteurized whole cow's milk, dry infant formula,
      stainless steel, plastic cutting board, ceramic tile, rubber sheets, and sealed
      concrete. The system consists of the MicroSEQ Listeria spp. Detection Kit, two
      sample preparation kits (PrepSEQ Nucleic Acid Extraction Kit and PrepSEQ Rapid
      Spin Sample Preparation Kit), the Applied Biosystems 7500 Fast Real-Time PCR
      instrument, and the RapidFinderTM Express v1.1 Software for data analysis. The
      test method was compared to the ISO 11290-1 reference method using an unpaired
      study design. The MicroSEQ Listeria spp. Detection Kit and the ISO 11290-1
      reference method showed equivalent detection based on Chi-square analysis for all
      matrixes except hot dogs. For hot dogs, the MicroSEQ method detected more
      positives than the reference method for the low- and high-level inoculations,
      with all of the presumptive positives confirmed by the reference method. An
      independent validation study confirmed these findings on lox and stainless steel
      surface. The MicroSEQ kit detected all 50 Listeria strains tested and none of the
      31 nontarget bacteria strains.

PMID- 22970576
TI  - Stability of aflatoxins in solution.
AB  - The stability of aflatoxins B1, B2, G1, and G2 was studied in solutions
      containing different concentrations of water, acetonitrile, and/or methanol, and
      in autosampler vials treated with nitric acid or silanized. When stored at room
      temperature (20 degrees C) for 24 h, aflatoxins G1 and G2 were stable only in
      solutions containing 100% organic solvent, whereas aflatoxins B1 and B2 were
      stable in solutions of methanol-water and acetonitrile-water at greater than 60
      and 40% organic content, respectively. At 5 degrees C, aflatoxins G1 and G2
      showed a significant decrease in concentration only when kept in less than 20%
      aqueous organic solvent. Significant loss of aflatoxins was realized in standard,
      commercially available amber type I borosilicate autosampler vials, but chemical
      etching of the vials with nitric acid or with silanization prevented aflatoxin
      degradation. These results indicate that aflatoxins are unstable in aqueous
      solutions and that this instability can be counteracted by the presence of at
      least 20% organic solvent and keeping the solutions at 5 degrees C or by the use
      of treated vials.

PMID- 22970577
TI  - Rapid liquid chromatography for paralytic shellfish toxin analysis using
      superficially porous chromatography with AOAC Official Method 2005.06.
AB  - The bioaccumulation of paralytic shellfish toxins in mussels, oysters, cockles,
      hard clams, razors, and king scallops is monitored in England, Scotland, and
      Wales by AOAC Official Method 2005.06 LC-with fluorescence detection (FLD). One
      of the commonly perceived disadvantages of using this method is the long
      turnaround time and low throughput in a busy laboratory environment. The
      chromatographic analysis of each sample typically utilizes a 15 min cycle time to
      achieve toxin oxidation product separation and column equilibration prior to
      subsequent analysis. A standard RP C18 analytical column, used successfully in
      recent years, achieves good separation with a long column lifetime. The analysis
      of a 40 sample qualitative screening batch takes approximately 18 h, including
      blanks, standards, and other QC samples. The availability of superficially porous
      column technology has offered the potential to reduce analysis time while
      retaining column performance on existing hardware. In this study, AOAC Official
      Method 2005.06 with LC-FLD was transferred to two different commercially
      available superficially porous columns, and the method performance
      characteristics were evaluated. Both columns separated all toxins adequately with
      cycle times less than half that of the existing method. Linearity for each toxin
      was acceptable up to two times the European maximum permitted limit of 800 microg
      di-HCl saxitoxin equivalent/kg flesh. LOD and LOQ values were substantially
      improved for the majority of toxins, with gonyautoxin 1&4 and neosaxitoxin
      showing up to a two- and fourfold improvement, respectively, depending on the
      column used. Quantification results obtained from parallel analysis of
      contaminated samples were acceptable on both columns. Comparative screen results
      gave a slight increase in the occurrence of contaminated samples, which was
      attributed to the improved detection limit for most toxins. Issues with rapidly
      increasing back pressure, however, were identified with both columns, with a
      limit of around 500 injections. This compares to the >3000 cycles routinely
      obtained with the standard RP-C18 HPLC columns currently in use. Overall, the
      gain achieved with these columns through shorter analysis time and improved
      analytical sensitivity is potentially of benefit in a high-throughput
      environment. For the routine high-throughput screening of shellfish samples,
      however, an improved column lifetime is desirable.

PMID- 22970578
TI  - Determination of brevetoxins in shellfish by LC/MS/MS: single-laboratory
      validation.
AB  - A single-laboratory validation is reported for an LC/MS/MS quantification of six
      brevetoxins in four matrixes (Greenshell mussel, eastern oyster, hard clam, and
      Pacific oyster). Recovery and precision data were collected from seven analytical
      batches using shellfish flesh at 0.05 mg/kg. Method recoveries and within
      laboratory reproducibility ranged from 73 to 112%, with an RSD between 14 and 18%
      for brevetoxin-3, brevetoxin B5, brevetoxin B2, and S-desoxy brevetoxin B2. The
      recovery and within-laboratory reproducibility for brevetoxin-2 was 61%, with an
      RSD of 27%. Brevetoxin B1 gave an RSD of 12%, but no reference material was
      available and this toxin was only recorded in a hard clam sample naturally
      contaminated with brevetoxins. One naturally contaminated sample of each
      shellfish matrix, with brevetoxin levels ranging from 0.012 to 9.9 mg/kg, was
      tested in multiple batches, and the RSDs were similar to those for fortified
      samples at 0.05 mg/kg. Comparisons with limited data for the neurotoxic shellfish
      poisoning mouse bioassay for four naturally contaminated shellfish samples showed
      that the regulatory action limit of 0.8 mg/kg is conservative with respect to the
      bioassay regulatory limit of 20 mouse units/100 g.

PMID- 22970579
TI  - EZ Gluten for the qualitative detection of gluten in foods, beverages, and
      environmental surfaces.
AB  - The EZ Gluten assay is a rapid immunochromatographic screening method for
      qualitative detection of gluten in raw and cooked foods and beverages and on
      environmental surfaces. This AOAC Performance Tested Method study evaluated the
      EZ Gluten assay as an effective method for the detection of gluten in four
      selected matrixes: rice flour, cooked dough, beer, and dog food. In addition, the
      method was evaluated for its effectiveness in detecting gluten contamination of >
      or =1 microg/2 in.2 (25 cm2) stainless steel surface area. The EZ Gluten
      demonstrated 100% specificity [probability of detection (POD) 0.00, confidence
      interval (CI) 0.00-0.01] and 99% sensitivity (POD 0.99, CI 0.97-0.995) at the 10
      ppm level for all four matrixes, and 100% specificity (POD 0.00, CI 0.00-0.11)
      and sensitivity (POD 1.00, CI 0.886-1.00) at the 1 microg level on the stainless
      steel surface. Independent laboratory testing confirmed the internal validation
      results in one matrix and on the stainless steel surface. Lot-to-lot, stability,
      and robustness studies provided evidence that the EZ Gluten is a rugged,
      consistent method for the detection of gluten at levels as low as 10 ppm.

PMID- 22970580
TI  - Gliadin as a measure of gluten in foods containing wheat, rye, and barley-enzyme
      immunoassay method based on a specific monoclonal antibody to the potentially
      celiac toxic amino acid prolamin sequences: collaborative study.
AB  - The Working Group on Prolamin Analysis and Toxicity (WGPAT) organized a
      collaborative study to confirm whether the two R5 antibody-based ELISA test kits
      are able to detect gliadin in the lower mg/kg (ppm) level. Twenty laboratories
      investigated 12 blind-coded samples, spiked and naturally contaminated, to show
      the possibility of determining traces of gliadin in heat-treated or nonheat
      treated foods by ELISA. It was shown that very small amounts of gliadin (below
      100 ppm) could be detected by ELISA with a reproducibility RSD(R) (37%) and a
      repeatability RSD, (27%) common for ELISA under these conditions. The recovery of
      gliadin from the spiked samples was between 84 and 109%, based on the results of
      all laboratories, including those with poor performance. No false positives were
      found by the method (P < or =0.05), but one negative sample was contaminated
      during the bakery process. It is recommended that the method be accepted by AOAC
      as Official First Action.

PMID- 22970581
TI  - Octadecyl-bonded silica membrane disk modified with Cyanex302 for pre
      concentration and determination of iron in food products.
AB  - A simple and rapid method using an octadecyl-bonded silica membrane disk
      impregnated with Cyanex302 is described for the pre-concentration and
      determination of iron. The influence of various parameters on sorption and
      elution of Fe(III) were systematically investigated. The sorption of Fe(III) at
      pH 3.2 was quantitative (99.3 +/- 1.1%). It was completely recovered using 20 mL
      5.0 M HCI and determined by flame atomic absorption spectrometry. Breakthrough
      volume of the modified disk for Fe(III) was >2000 mL, pre-concentration factor
      was >100, and reusability up to 28 cycles. The LOD and LOQ for Fe(III) were 0.45
      microg/L and 1.51 microg/L, respectively, while precision for its determination
      in terms of RSD was < or =2.1%. This method was applied for Fe(III) determination
      in milk, fortified flour, cocoa powder, tea, and black pepper. To validate the
      procedure, EPA Method Standard (QC standard 21) was analyzed for Fe(III).

PMID- 22970582
TI  - Development of dipsticks for simultaneous detection of vip3A and cry1Ab/cry1Ac
      transgenic proteins.
AB  - The number of genetically modified (GM) crops being cultivated and its produce
      reaching market is increasing every year. The transgenes (vip3A, cry1Ab, and
      cry1Ac) from Bacillus thuringiensis are being used by plant breeders, apart from
      other transgenes for developing insect pest-resistant GM crops. It is therefore
      necessary to develop an easy, rapid, and reliable detection assay to discriminate
      GM crops and non-GM crops. Dipstick strips using colloidal gold-labeled
      polyclonal antibodies were developed for simultaneous detection of Vip3A and
      Cry1Ab/CrylAc proteins. The assay was essentially based on the sandwich format of
      immunoassay, which was completed within 10 min, and the results were evaluated
      visually. The detection limits were 50 ng/mL (50 ppb) for both CrylAc and CrylAb
      proteins, and 100 ng/mL (100 ppb) for Vip3A protein. The developed dipsticks are
      suitable for on-site simultaneous screening of GM crops bearing two proteins,
      which, in turn, reduce cost and time of the assay.

PMID- 22970583
TI  - Determination of trigonelline, nicotinic acid, and caffeine in Yunnan Arabica
      coffee by microwave-assisted extraction and HPLC with two columns in series.
AB  - A simple, rapid method was developed for simultaneous extraction of trigonelline,
      nicotinic acid, and caffeine from coffee, and separation by two chromatographic
      columns in series. The trigonelline, nicotinic acid, and caffeine were extracted
      with microwave-assisted extraction (MAE). The optimal conditions selected were 3
      min, 200 psi, and 120 degrees C. The chromatographic separation was performed
      with two columns in series, polyaromatic hydrocarbon C18 (250 x 4.6 mm id, 5
      microm particle size) and Bondapak NH2 (300 x 3.9 mm id, 5 microm particle size).
      Isocratic elution was with 0.02 M phosphoric acid-methanol (70 + 30, v/v) mobile
      phase at a flow rate of 0.8 mL/min. Good recoveries and RSD values were found for
      all analytes in the matrix. The LOD of the three compounds was 0.02 mg/L, and the
      LOQ was 0.005% in the matrix. The concentrations of trigonelline, nicotinic acid,
      and caffeine in instant coffee, roasted coffee, and raw coffee (Yunnan Arabica
      coffee) were assessed by MAE and hot water extraction; the correlation
      coefficients between concentrations of the three compounds obtained were close to
      1.

PMID- 22970584
TI  - A liquid chromatography method for determination of selected amino acids,
      coenzymes, growth regulators, and vitamins from Cicer arietinum (L.) and Solanum
      lycopersicum (L.).
AB  - A bottleneck in crosstalk and QC research has been the quantification of diverse
      chemotypes in small amounts of tissue. An LC-UV method for estimating 28 selected
      metabolites of the regulatory network underlying growth, development,
      maintenance, vital functions, defense reactions, and food quality is reported.
      The method was based on binary gradient resolutions of the analytes in an RP C18
      column. The mobile phase comprised solvent A [water+0.1% trifluoroacetic acid
      (TFA)] and B (acetonitrile + 0.085% TFA at a flow rate of 1 ml/min. Twenty-three
      metabolites (selected amino acids, coenzymes, growth regulators, phenolic
      antioxidant, and water-soluble vitamins) were detected at 254 nm, and four fat
      soluble vitamins at 280 nm. Jasmonic acid was quantified at 210 nm. The RSDs of
      peak area and retention time for each metabolite were <5.8%. The calibration
      graphs were linear with R2 values ranging from 0.98 to 0.99. The LODs (microg/mL)
      were about 0.01-1.0 for 23 metabolites quantified at 254 nm, 0.1-0.2 for fat
      soluble vitamins, and 0.1 for jasmonic acid. The recoveries ranged from 80 to
      105%, with RSDs of 2.8 to 11.2%. The method has been satisfactorily applied for
      determination of 28 metabolites from Cicer arietinum (L.) and Solanum
      lycopersicum (L.). It could be an alternative and competitive method of choice
      that can cheaply and easily perform routine analysis for food quality and
      targeted metabolomics of chickpea and tomato in response to stressors.

PMID- 22970585
TI  - Determination of flavanol and procyanidin (by degree of polymerization 1-10)
      content of chocolate, cocoa liquors, powder(s), and cocoa flavanol extracts by
      normal phase high-performance liquid chromatography: collaborative study.
AB  - An international collaborative study was conducted on an HPLC method with
      fluorescent detection (FLD) for the determination of flavanols and procyanidins
      in materials containing chocolate and cocoa. The sum of the oligomeric fractions
      with degree of polymerization 1-10 was the determined content value. Sample
      materials included dark and milk chocolates, cocoa powder, cocoa liquors, and
      cocoa extracts. The content ranged from approximately 2 to 500 mg/g (defatted
      basis). Thirteen laboratories representing commercial, industrial, and academic
      institutions in six countries participated in the study. Fourteen samples were
      sent as blind duplicates to the collaborators. Results from 12 laboratories
      yielded repeatability relative standard deviation (RSDr) values that were below
      10% for all materials analyzed, ranging from 4.17 to 9.61%. The reproducibility
      relative standard deviation (RSD(R)) values ranged from 5.03 to 12.9% for samples
      containing 8.07 to 484.7 mg/g. In one sample containing a low content of
      flavanols and procyanidins (approximately 2 mg/g), the RSD(R) was 17.68%. Based
      on these results, the method is recommended for Official First Action for the
      determination of flavanols and procyanidins in chocolate, cocoa liquors,
      powder(s), and cocoa extracts.

PMID- 22970586
TI  - Lipid profile of in vitro oil produced through cell culture of Jatropha curcas.
AB  - Recent increases in energy demands as a consequence of population growth and
      industrialization, and pollution caused during the extraction and combustion of
      fossil fuel sources have driven the development of new energy sources that do not
      cause pollution and are inexpensive and renewable. Consequently, it is necessary
      to develop alternative ways of generating biofuels that put less pressure on
      agricultural lands and water supplies, and ensure ecosystems conservation. In
      order to achieve the proposed goals related to energetic coverage and
      independence, several approaches have been developed, including biodiesel
      production using vegetal oils as feedstock. The aim of the current research
      project was to apply a nonconventional bioprocess for in vitro biomass and oil
      production of Jatropha curcas, for assessing different J. curcas varieties, where
      seed tissue was isolated and used for callus induction. Once friable callus was
      obtained, cell suspension cultures were established. The cell viability, fatty
      acid content, and characteristics were used to select the most promising cell
      line according to its fatty acid profile and ability to grow and develop under in
      vitro conditions. Oil produced by cell suspension culture of the Jatropha
      varieties studied was extracted and characterized by GC/MS. Differences
      encountered among Jatropha varieties were related to their fatty acid profiles,
      oil content (% on dry basis), and cell viability measurements (%).

PMID- 22970587
TI  - Cloud point extraction of copper, lead, cadmium, and iron using 2,6-diamino-4
      phenyl-1,3,5-triazine and nonionic surfactant, and their flame atomic absorption
      spectrometric determination in water and canned food samples.
AB  - A cloud point extraction procedure was optimized for the separation and
      preconcentration of lead(II), cadmium(II), copper(II), and iron(III) ions in
      various water and canned food samples. The metal ions formed complexes with 2,6
      diamino-4-phenyl-1,3,5-triazine that were extracted by surfactant-rich phases in
      the nonionic surfactant Triton X-114. The surfactant-rich phase was diluted with
      1 M HNO3 in methanol prior to its analysis by flame atomic absorption
      spectrometry. The parameters affecting the extraction efficiency of the proposed
      method, such as sample pH, complexing agent concentration, surfactant
      concentration, temperature, and incubation time, were optimized. LOD values based
      on three times the SD of the blank (3Sb) were 0.38, 0.48, 1.33, and 1.85 microg/L
      for cadmium(II), copper(II), lead(II), and iron(III) ions, respectively. The
      precision (RSD) of the method was in the 1.86-3.06% range (n=7). Validation of
      the procedure was carried out by analysis of National Institute of Standards and
      Technology Standard Reference Material (NIST-SRM) 1568a Rice Flour and GBW 07605
      Tea. The method was applied to water and canned food samples for determination of
      metal ions.

PMID- 22970588
TI  - Development of an analytical method for antimony speciation in vegetables by HPLC
      hydride generation-atomic fluorescence spectrometry.
AB  - A new method for antimony speciation in terrestrial edible vegetables (spinach,
      onions, and carrots) was developed using HPLC with hydride generation-atomic
      fluorescence spectrometry. Mechanical agitation and ultrasound were tested as
      extraction techniques. Different extraction reagents were evaluated and optimal
      conditions were determined using experimental design methodology, where EDTA (10
      mmol/L, pH 2.5) was selected because this chelate solution produced the highest
      extraction yield and exhibited the best compatibility with the mobile phase. The
      results demonstrated that EDTA prevents oxidation of Sb(III) to Sb(V) and
      maintains the stability of antimony species during the entire analytical process.
      The LOD and precision (RSD values obtained) for Sb(V), Sb(III), and trimethyl
      Sb(V) were 0.08, 0.07, and 0.9 microg/L and 5.0, 5.2, and 4.7%, respectively, for
      a 100 microL sample volume. The application of this method to real samples
      allowed extraction of 50% of total antimony content from spinach, while antimony
      extracted from carrots and onion samples ranged between 50 and 60 and 54 and 70%,
      respectively. Only Sb(V) was detected in three roots (onion and spinach) that
      represented 60-70% of the total antimony in the extracts.

PMID- 22970589
TI  - Determination of traces of iron and lead in food and water samples after
      preconcentration on multiwalled carbon nanotubes.
AB  - A new method using multiwalled carbon nanotubes as an SPE adsorbent was developed
      for the sensitive determination of trace iron and lead prior to flame atomic
      absorption spectrometry analysis. Iron and lead as 2,9-dimethyl-4,7-diphenyl-1,10
      phenanthroline chelates were adsorbed quantitatively on multiwalled carbon
      nanotubes at a pH of 6.0 and easily eluted with 10 mL 1 M HNO3. The influences of
      matrix ions were also examined. The LOD values for iron and lead were calculated
      as 1.3 and 2.9 microg/L, respectively. Validation of the presented procedure was
      performed by the analysis of TMDA 54.4 fortified lake water and HR-1 Humber River
      sediment certified reference materials. The method was successfully applied to
      the determination of trace iron and lead in real environmental samples, and
      excellent results were achieved.

PMID- 22970590
TI  - A method for the routine determination of methylmercury in marine tissue by GC
      isotope dilution-ICP-MS.
AB  - Currently, there is no legal limit for methyl mercury (MeHg) in food; thus, no
      standardized method for the determination of MeHg in seafood exists within the
      European jurisdiction. In anticipation of a future legislative limit an
      inductively coupled plasma isotope dilution mass spectrometry (GC-ICP-ID-MS)
      method was developed in collaboration with the European Standardization
      Organization (CEN). The method comprises spiking the tissue sample with Me201Hg,
      followed by decomposition with tetramethylammonium hydroxide, pH adjustment and
      derivatization with sodium tetraethylborate, and finally organic extraction of
      the derivatized MeHg in a hexane phase. Subsequently, the sample is analyzed via
      GC-ICP-MS and the result calculated using the ID equation. The working range of
      the method was 0.0005-1.321 mg/kg MeHg in marine tissue, with an internal
      reproducibility (RSD) of 12-1%. The method was validated based on statistical
      measures, such as the z-scores, using the commercially available reference
      materials from National Institute of Standards and Technology Standard Reference
      Material (NIST SRM) 1566b, NIST SRM 2977 and National Research Council of Canada
      (NRCC) TORT 2, NRCC, DORM 3, NRCC DOLT 4, and European Reference Material (ERM)
      CE 464. Z-scores for all standard reference materials, except for NIST SRM 1566b,
      were better than 11.51. The wide range of marine tissues used during the
      validation ensures that the method will be applicable for measuring of MeHg in
      seafood matrixes of all kinds.

PMID- 22970591
TI  - Determination and assessment of estradiol-mimicking compounds in the dissolved
      and particulate phases of wastewater treatment plant samples.
AB  - During the last two decades, a large number of publications have clearly shown
      that anthropogenic compounds that disrupt the endocrine system of wildlife
      species are a major cause for concern, and this concern has led to a demand for
      new screening methods. In this work, we have optimized and applied a new method
      to identify endocrine-disrupting chemicals (EDCs), such as nonylphenol,
      octylphenol, and their corresponding ethoxylates, 17alpha-ethynylestradiol,
      bisphenol-A, 17beta-estradiol, and estriol, in sewage samples. For the extraction
      and preconcentration of all analytes from the dissolved and particulate phases,
      we used SPE and ultrasonic assisted extraction, respectively. Identification and
      quantification were achieved by HPLC with fluorescence detection. Satisfactory
      LODs (between 0.5 and 7.6 ng/L in the dissolved phase and 12.3 and 21.4 ng/g in
      the particulate phase) and analyte recoveries (between 67 and 102%) were achieved
      for the target compounds. The optimized method was applied to the determination
      of EDCs in liquid sewage samples collected from July 2009 to July 2010 from a
      wastewater treatment plant in Las Palmas de G.C. (Spain). Concentrations of EDCs
      ranged from <10 to nearly 1300 ng/L in the dissolved phase, and from 0.1 to 7.7
      microg/g in the suspended particulate matter.

PMID- 22970593
TI  - Validation study of the BetaStar plus lateral flow assay for detection of beta
      lactam antibiotics in milk.
AB  - A validation study designed to meet the requirements of the AOAC Research
      Institute and the U.S. Food and Drug Administration, Center for Veterinary
      Medicine (FDA/CVM) was conducted for a receptor and antibody-based,
      immunochromatographic method (BetaStar Plus) for detection of beta-lactam
      antibiotic residues in raw, commingled bovine milk. The assay was found to detect
      amoxicillin, ampicillin, ceftiofur, cephapirin, cloxacillin, and penicillin G at
      levels below the FDA tolerance/safe levels, but above the maximum sensitivity
      thresholds established by the National Conference on Interstate Milk Shipments
      (NCIMS). Results of the part I (internal) and part II (independent laboratory)
      dose-response studies employing spiked samples were in close agreement. The test
      was able to detect all six drugs at the approximate 90/95% sensitivity levels
      when presented as incurred residues in milk collected from cows that had been
      treated with the specific drug. Selectivity of the assay was 100%, as no false
      positive results were obtained in testing of 1031 control milk samples. Results
      of ruggedness experiments established the operating parameter tolerances for the
      BetaStar Plus assay. Results of cross-reactivity testing established that the
      assay detects certain other beta-lactam drugs (dicloxacillin and ticarcillin),
      but it does not cross-react with any of 30 drugs belonging to other classes.
      Abnormally high bacterial or somatic cell counts in raw milk produced no
      interference with the ability of the test to detect beta-lactams at
      tolerance/safe levels.

PMID- 22970592
TI  - Sorbent extraction of Pb(II), Cu(II), Ni(II), and Fe(III) ions as 2-(5-bromo-2
      pyridylazo)-5-diethylamino-phenol chelates on single-walled carbon nanotube disks
      prior to their flame atomic absorption spectrometric determinations in animal
      feeds and natural water samples.
AB  - A sorbent extraction procedure for Pb(II), Cu(II), Ni(II), and Fe(III) ions on
      single-walled carbon nanotube disks has been established. Analyte ions were
      converted to 2-(5-bromo-2-pyridylazo)-5-diethylamino-phenol chelates, then
      adsorbed on the disk. Adsorbed chelates were easily desorbed from the disk by
      using 10 mL 2 M HNO3. The various analytical parameters, including pH and reagent
      amounts that were effective for the recoveries of the analytes on nanotube disks,
      were optimized. The influence of matrix ions was also studied. The LOD values
      based on 3sigma were in the 0.3-4.6 microg/L range. Validation of the proposed
      SPE procedure was carried out by the determination of analytes in certified
      reference materials (TMDA-54.4 fortified lake water and HR-1 Humber River
      sediment). Spiking and recovery experiments for the analyte ions in real samples
      gave good results. Application of the procedure was illustrated by the
      determination of analyte contents in some animal feeds and water samples from
      Turkey.

PMID- 22970595
TI  - Controversy continues around the AHA statement.

PMID- 22970594
TI  - Determination of total nitrofuran metabolites in shrimp muscle using liquid
      chromatography/tandem mass spectrometry in the atmospheric pressure chemical
      ionization mode.
AB  - The method of MacMahon and Lohne for analysis of nitrofuran metabolites in shrimp
      was optimized to streamline the extraction processes and the LC analysis. This
      revised method includes 16 h of mild acid hydrolysis/derivatization followed by
      ethyl acetate extraction and analysis by LC/MS/MS in the atmospheric pressure
      chemical ionization mode. This revised method was validated in shrimp for
      concentrations of 0.25 to 2.0 ng/g. The LOQ was 0.25 ng/g for all metabolites.
      The LOD was 0.052 nglg for 1-aminohydantoin (AHD), 0.206 ng/g for 3-amino-2
      oxazolidinone (AOZ), 0.108 ng/g for semicarbazide (SC), and 0.062 ng/g for 3
      amino-5-morpholinomethyl-2-oxazolidinone (AMOZ). The spike recoveries with RSD
      into negative matrix at 1 ng/g were 100.2% (3.2%) for AHD, 102.5% (1.0%) for AOZ,
      103.7% (2.3%) for SC, and 104.0% (3.3%) for AMOZ. The spike recoveries at 1 ng/g
      into unknown samples (n=108) containing varied levels of nitrofuran metabolites
      were 112.6% (25.7%) for AHD, 108.1% (12.1%) for AOZ, 103.0% (12.0%) for SC, and
      100.3% (6.9%) for AMOZ. Interday precision with samples containing incurred AOZ
      concentrations of 0.92 to 17.8 ppb performed over a year was 10.4% RSD. The
      method is accurate and precise for determining nitrofuran concentrations in the
      edible tissue of shrimp.

PMID- 22970596
TI  - Semantics undermines the oral-systemic disease message.

PMID- 22970597
TI  - Focus on: Implant dentistry.

PMID- 22970598
TI  - Intraoral radiography and dental implant restoration.
AB  - The usefulness of IOR has been described along with its limitations when
      considering implant restorations. One major issue is the alignment of the
      incident x-rays so that they are consistently perpendicular to the implant body,
      to provide the most reliable information possible. Other limitations include
      inconsistencies as a result of the inability to verify the nature and extent of
      bone around an implant, which is subject to variation as a result of type of bone
      and site. Where implants are concerned, as a diagnostic tool IOR should be
      considered as part of a multitude of tests-including probing, mobility, symptoms,
      and other soft-tissue evaluations. It must be emphasized that IOR cannot be
      relied upon as being the sole diagnostic test.

PMID- 22970599
TI  - The CT/CBCT-based team approach to care. Part I: Identiying the implant patient
      and prosthetic options.
AB  - Through a CBCT-based team meeting, the surgical team, restorative dentist, and
      laboratory team member can better coordinate dental implant treatment on many
      levels. Once the desired restorative result has been established through
      conventional means, the information can then be transferred via a radiographic
      template during the scan acquisition. The type of implant, angulation, width and
      diameter of the implant, and need for grafting, can be determined with great
      accuracy. This effective exchange of information can take place during an online
      meeting at a convenient time for all parties. The treatment planning that is
      possible within the framework of this digital workflow defines the essence of a
      team approach to implant reconstruction. The protocol as described in part I of
      this 3-part series allows for improved diagnosis, treatment planning, and
      successful clinical outcomes. Part 2 of this series will focus on the surgical
      aspects of the team approach, in collaboration with the restorative clinician and
      diagnostic imaging center.

PMID- 22970600
TI  - Predictable stabilization of a lower denture.

PMID- 22970601
TI  - Differential diagnosis of toothache pain. Part 2, nonodontogenic etiologies.
AB  - A variety of pain disorders involve the head, neck, jaws, and face. Many
      contradicting symptoms may exist when a patient presents with multiple problems.
      In order to diagnose and treat dental disease, a thorough understanding of both
      odontogenic and nonodontogenic etiologies of toothache pain is paramount. Harvey
      McGehee, a noteworthy medical diagnostician, wrote: "In making the diagnosis of
      the cause of illness in an individual case, calculations of probability have no
      meaning. The pertinent question is whether the disease is present or not. Whether
      it is rare or common does not change the odds in a single patient. If the
      diagnosis can be made on the basis of specific criteria, then these criteria are
      either fulfilled or not fulfilled." Good diagnosticians in all fields of medicine
      are on the endangered species list. To become a successful diagnostician, one
      needs to have interest, intuition, curiosity, patience, and a quest for
      knowledge. Each day presents a new opportunity and you can either be the goat, or
      the GOAT (greatest of all time). The choice is yours.

PMID- 22970602
TI  - Full-mouth reconstruction: The importance of treatment planning in restoring
      aesthetics and function.

PMID- 22970603
TI  - Histological layering technique for composites.

PMID- 22970604
TI  - WHO Expert Committee on Leprosy.
AB  - Since the introduction of multidrug therapy for leprosy in 1981, an estimated 15
      million patients have been cured of the disease and disabilities have been
      prevented in some 2-3 million individuals. These remarkable results have been
      brought about by the synergistic efforts of WHO, governmental and nongovernmental
      bodies, academia, industry and affected communities throughout the world.
      Nevertheless, much remains to be done--both to sustain this progress and to
      effect a further reduction in the impact of leprosy on patients and their
      families. This report presents the conclusions and recommendations of the WHO
      Expert Committee on Leprosy, whose eighth meeting reflected the recent shift in
      emphasis of leprosy elimination to reducing of the impairments and disabilities
      caused by the disease and ensuring the quality and sustainability of leprosy
      services. The Committee analysed the global leprosy situation, discussed elements
      of epidemiology, and reviewed developments in treatment of the disease and
      management of complications. Sociocultural issues were addressed, as was the need
      for community care, accessibility of health services, and effective referral
      systems. Indicators for monitoring and evaluation were outlined and research
      priorities were set out.

PMID- 22970605
TI  - [Plasma copeptin--a multi-purpose diagnostic tool for clinicians?].
AB  - Measurement of antidiuretic hormone (ADH) is utilized in the diagnosis of
      hyponatremia and polyuria. However, determination of ADH is slow, and results may
      be unreliable. Copeptin is a glycopeptide of 39 amino acid residues that is
      cleaved from a precursor of ADH and secreted to the circulation in an equimolar
      manner with ADH. Determination of the copeptin level is quick and reliable, and
      improves the diagnostics of osmotic disorders. Copeptin seems to be a promising
      diagnostic tool also in acute coronary syndrome and may have prognostic
      significance in cardiac insufficiency, stroke or septicaemia, too.

PMID- 22970606
TI  - [Primary biliary cirrhosis (PBC)].
AB  - Primary biliary cirrhosis (PBC) is an inflammatory autoimmune liver disease
      leading, if untreated, to cholestasis and cirrhosis. The diagnosis is made on the
      basis of elevated plasma levels of alkaline phosphatase and antimitochondrial
      antibodies at a stage where the patient usually still remains symptomless. The
      degree of severity and prognosis of the disease are defined by means of
      histological findings of the liver. Adequate response for approximately half of
      the patients is obtained with urodeoxycholic acid treatment. The treatment for
      advanced disease is hepatic transplantation, which yields excellent results.

PMID- 22970607
TI  - [GRACILE syndrome--a severe neonatal mitochondrial disorder].
AB  - GRACILE syndrome belongs to the Finnish disease heritage, and is caused by a
      point mutation in the BCS1L-gene encoding a mitochondrial protein. This leads to
      dysfunction of the complex III in the respiratory chain. Significant fetal growth
      disturbance is the primary manifestation. Within the first day the newborn infant
      develops severe lactic acidosis. Hypoglycemia, elevated serum ferritin and
      conjugated bilirubin values and aminoaciduria imply mitochondrial liver disease
      and renal tubulopathy. In Finland, the diagnosis is based on the 232A>G mutation
      in the BCS1L-gene. No specific treatment is available. GRACILE syndrome leads to
      early death.

PMID- 22970608
TI  - [Treatment of infertility--part II (male infertility)].
AB  - The main cause for male infertility is oligo-azoospermia. Correct etiological
      diagnosis of azoospermia is important. If sperm analysis is abnormal, an
      endocrinological evaluation should be performed. The causes for azoospermia can
      be divided into obstructive and non-obstructive causes; the differential
      diagnosis is based on the levels of serum gonadotropins and testosterone. A
      frequent cause for azoospermia is the use of testosterone or anabolic steroids.
      However, spermatogenesis generally recovers spontaneously after discontinuing the
      medication. For other cases of oligo/azoospermia, the most commonly used
      treatment modalities or antiestrogens, and testicular sperm aspiration or
      microscopic testicular sperm extraction in association with intracytoplasmic
      sperm injection.

PMID- 22970609
TI  - [Treatment of prolonged migraine attack (status migrenosus)].
AB  - If a migraine attack takes more than 72 hours it is called status migrenosus
      (SM). The most important contributing factor in SM is prolonged excessive use of
      anti-migraine drugs. Before starting any treatments for SM, severe causes
      underlying the prolonged pain should be excluded. The cornerstones of
      pharmacological therapy for SM are parenterally administered anti-inflammatory
      drugs and triptans as well as valproate and dopamine antagonists. With regard to
      long-term prognosis, the recognition and treatment of medication overuse headache
      is essential.

PMID- 22970610
TI  - [Structured electronic consultation letter for shoulder disorders].
AB  - Referral to a specialist has a significant influence on management of the patient
      and costs associated with the treatments. However, development and research of
      the process by which patients are referred has been almost neglected.
      Expectations considering the purpose, contents, and timing of the referral of the
      consulting physician and the consultant do not always meet. A structured,
      electronic consultation letter was developed to respond this need. Functionality
      and interactivity are the key elements of the referral, including (1) an
      electronic referral letter to a specialist, (2) interactive education in clinical
      examination and management of shoulder disorders, and (3) an instrument of
      clinical examination and documentation of shoulder disorders.

PMID- 22970611
TI  - [Referrals of knee osteoarthritis patients to orthopedic surgery].
AB  - BACKGROUND: Due to large volume of knee osteoarthritis referrals and increasing
      waiting times, the contents of referrals and patient's pathways were analyzed in
      the Jyvaskyla Central Hospital. METHODS: The referral contents of 171 knee
      osteoarthritis patients referred to the orthopedic outpatient clinic were
      screened, and the post-referral treatment decisions were pulled from the medical
      records. OUTCOME: Most of the referrals had information about the diagnosis
      (90%), pain (88%) and symptom duration (80%). The least frequently mentioned were
      BMI (3%) and the implementation of conservative treatment (7%). During the
      specialist visit following the referral, 62% of the patients ended up in
      operative and 38% in conservative treatment. There was no connection between the
      referral contents and the line of treatment chosen. CONCLUSIONS: Conservative
      treatment of knee osteoarthritis should be optimized prior to referral to
      specialist care.

PMID- 22970612
TI  - [REM sleep behavior disorder (RBD)].
AB  - REM sleep behavior disorder (RBD) is one of the most important factors predicting
      Parkinson's disease. Symptoms constitute vivid dreams typically characterized by
      ominous contents and associated muscular activity. Specific signs include the
      preservation of muscle tone during REM sleep as detected in polysomnography, and
      behavior associated with dreaming as demonstrated by video monitoring. Injury
      risk is increased during the attacks. Melatonin or clonazepam can be used as
      therapy. The disorder belongs to the entity of synucleinopathies.

PMID- 22970613
TI  - [Update on current care guidelines: psoriasis and psoriatic arthritis].
AB  - Psoriasis is a chronic, immune-mediated, inflammatory disorder of the skin and
      joints. Moderate-to-severe cases are associated with an independent risk of
      comorbidity (cardiovascular diseases and diabetes) even after adjusting for risk
      factors, known to be more prevalent in psoriatics compared to normal population.
      The underlying systemic inflammation, analogous to that observed in rheumatoid
      arthritis, calls for a long-term effective treatment. Screening and treatment of
      cardiovascular risk factors is highly recommended. The biologic drug arsenal has
      new additions. Long term treatment data from clinical study extensions and
      independent registries are reviewed.

PMID- 22970614
TI  - Staffing benchmarks: a model for determining how many security officers are
      enough.
AB  - The authors describe the development of a model which assists with answering the
      question, "for a facility with certain characteristics, what would be the
      industry average number of security FTE's?" Through the use of multiple
      regression analysis using actual field data, an objective means of making this
      determination is possible, they report.

PMID- 22970615
TI  - A well-planned security program can help determine FTE needs.
AB  - Determining how many officers you need is not a simple process, the author points
      out. Achieving an effective and budget-wise solution is a continuous process that
      needs to be evaluated and re-evaluated over time. In this article he reviews the
      many factors that have to be considered.

PMID- 22970616
TI  - Public safety training as a force multiplier.
AB  - The training of public safety officers to meet the many and varied demands of
      today's healthcare environment is the second step in developing and maintaining a
      world class public safety service. Working closely with the corporate training
      department, and utilizing the latest adult education techniques, the public
      safety director can ensure that all officers are capable of meeting the
      challenges threatening the safety and security of his healthcare facilities. This
      is the second in a series of articles on all aspects of public safety personnel
      administration.

PMID- 22970617
TI  - Security's role in PFCC.
AB  - Challenged by a clinical colleague, the author spells out the critical role
      Security plays in PFCC (Patient and Family Centered Care) at his institution and
      describes how, by taking an active role in the adoption of PFCC, Security can
      enhance its image within the health system.

PMID- 22970618
TI  - A customer service journey.
AB  - Converting security team members from simple rule enforcers to superior customer
      service providers required changes in leadership attitudes, rules, training, and
      other security traditions, but it has paid off in staff performance and
      recognition, according to the author.

PMID- 22970619
TI  - Developing and implementing a security plan in a non-typical healthcare facility.
AB  - Security for a healthcare facility which does not have an emergency department
      presents a different set of challenges for the security director. In this
      article, the author describes how a major Medical and Research hospital is
      meeting those challenges.

PMID- 22970620
TI  - Workplace violence prevention: team collaboration is the key.
AB  - By involving managers of other departments in a cross-functional team to address
      the many and varied problems involved in dealing with workplace violence, the
      author is able to report more efficient management of the prevention process,
      expanded program oversight without the commitment of additional resources, and a
      well-balanced solution approach to the causes and outcomes of workplace violence
      incidents.

PMID- 22970621
TI  - How to prevent workplace violence incidents and improve security using baseline
      security assessments.
AB  - To meet state and OSHA requirements for dealing with and reporting workplace
      violence, a growing number of hospitals, the author reports, are turning to
      baseline workplace violence assessments which survey employees in different
      roles, combined with a threat analysis and an analysis of existing controls and
      historical incidents that can be reviewed and tracked over time to show
      improvement or decline.

PMID- 22970622
TI  - Handling restraining orders in a health-related facility.
AB  - Having an effective restraining order policy in place, besides contributing to
      professionalizing the image of the security department, provides greater
      protection for victims and staff while lessening your organization's liability,
      according to the authors, who present a primer in managing such orders.

PMID- 22970623
TI  - Forensic patients--who is watching them?
AB  - Does your hospital security department have the right and/or responsibility for
      checking out the qualifications and practices of private contractors hired by law
      enforcement to guard forensic patients? In this article, the author explains why
      you should.

PMID- 22970624
TI  - Preparing a well-written report: an essential skill for the public safety
      officer.
AB  - In this basic introduction and refresher to the art of report writing, the author
      points out that, besides the importance of the report to the successful handling
      on an incident, public safety officer reports have a direct relationship to their
      professionalism. He stresses that sloppy, incomplete and/or incorrect reports can
      further a perception that the officer is an incompetent and/or ineffective public
      safety officer.

PMID- 22970625
TI  - Gangs and healthcare security: preparation and education are the keys.
AB  - The threat of gang violence spilling over into hospital emergency rooms has
      become a reality in communities of all sizes, the author reports. The keys to a
      successful campaign against gang violence in a hospital setting, he says, are
      training and education of security and clinical staffs, cooperation with law
      enforcement, and proper reporting procedures and protocols.

PMID- 22970626
TI  - Your hospital is moving: concerns for the security leader.
AB  - The security staff is the key to the successful move of an entire hospital to a
      new facility, the author says. Planning for the move will force a security
      department to take on issues that have never been considered, he adds. In this
      article, he presents those security and safety issues for managers and directors
      to thoroughly examine and review.

PMID- 22970627
TI  - Moving day: a case history.
AB  - Utilizing an Incident Command structure and organizational chart, a health system
      successfully moved 144 patients and related services to a new facility 3.5 miles
      away in four hours. In this article, the author describes the planning that was
      involved and the key role that was played by the Security Department.

PMID- 22970628
TI  - The varied roles of the crime prevention expert.
AB  - Whether you want to hire a crime prevention expert or become one, this article
      gives you the answers to the many questions asked about the roles played by such
      practitioners.

PMID- 22970629
TI  - Healthcare standards compliance--a timely primer.
AB  - This article attempts to provide a better understanding of the plethora of
      programs, policies, and procedures employed by governmental and other agencies
      which regulate healthcare facilities and impact on security and safety.

PMID- 22970630
TI  - Critical infrastructure protection.
AB  - Current government policies for protecting the nation's critical infrastructure
      are described in this article which focuses on hospital disaster planning and
      incident management and the significant role of Security in infrastructure
      protection

PMID- 22970631
TI  - If Disney ran your security department.
AB  - This article describes a program that has built relationships for the Security
      Department using customer service techniques which have added value to the
      hospital and the surrounding community.

PMID- 22970632
TI  - Insider threats: the myths, truths and tactics for mitigation.
AB  - The authors, executives of a leading risk management firm, confirm that breaches
      of data security are primary low-tech in nature and provide suggestions on how
      hospitals can deal with them.

PMID- 22970633
TI  - [Adequate use of parenteral antibacterial agents: panipenem/betamipron
      (discussion)].

PMID- 22970634
TI  - [Current candidiasis topics: monitoring Liposomal amphotericin B using
      candidiasis flow charts (discussion)].

PMID- 22970635
TI  - [The 7th Tokyo Infectious Disease in Hematology: antibiotic resistant bacteria].

PMID- 22970636
TI  - [Broadening the search in microbial/ fungal resources for new bioactive
      compounds].

PMID- 22970637
TI  - Displaced femoral neck stress fractures in Royal Marine recruits--management and
      results of operative treatment.
AB  - Femoral neck stress fractures (FNSF) represent 3.5%-8% of stress fractures in
      military recruits; potentially resulting in medical discharge and/or
      complications. The incidence of displaced FNSF in the British Army has been
      reported as 1.8 in 10,000 recruits. We aimed to review the incidence and outcome
      of displaced FNSF in Royal Marine recruits. Retrospective review identified 6
      recruits who sustained a displaced FNSF from 2001 to 2011 representing an
      incidence of 9.3 in 10,000 recruits. All were treated urgently by internal
      fixation. There were no cases of avascular necrosis, no surgical complications
      and no further procedures required. All united with a mean time to union of 11
      months. 50% had a union time greater than 1 year. These fractures are slow to
      unite but with urgent surgical intervention and stable fixation 100% union was
      achieved. Awareness of this guides the management and rehabilitation whilst
      avoiding the risks of unnecessary secondary surgical interventions.

PMID- 22970638
TI  - The primary care diagnosis and management of bulimia nervosa and its relevance in
      the UK Armed Forces.
AB  - Bulimia Nervosa is an eating disorder that is frequently seen in the UK Armed
      Forces population. In this article the diagnosis, management and clinical
      considerations of managing this condition in Primary Care in the UKArmed Forces
      are considered. The occupational and operational considerations for the military
      environment are also discussed.

PMID- 22970639
TI  - Case report of therapeutic cupping.

PMID- 22970640
TI  - Aggressive soft tissue infections and amputation in military trauma patients.
AB  - Due to the nature of IED injuries, during the conflicts in Iraq and Afghanistan
      The traditional, two-stage amputation for unsalvageable combat lower limb
      injuries has evolved into a strategy of serial debridement and greater use of
      plastic surgical techniques in order to preserve residual limb length. This study
      aimed to characterise the current treatment of lower limb loss with particular
      focus on the impact of specific wound infections. The UK military trauma registry
      and clinical notes were reviewed for details of all lower limb amputation
      identifying: 51 patients with 70 lower limb amputations. The mean number of
      debridements per stump prior to closure was 4.1 (95% CI 3.5-4.7). A final more
      proximal amputation level was required in 21 stumps (30%). Recovery of A.
      hydrophillia from wounds was significantly associated with a requirement for a
      more proximal amputation level (p=0.0038) and greater number of debridements
      (p=0.0474) when compared to residual limb wounds withoutA. hydrophillia.

PMID- 22970641
TI  - Significant neurological presentations in commando trained personnel: case
      studies and consideration of differential diagnosis.
AB  - A 27-year-old Royal Marine presented to his sickbay following two episodes of
      sudden onset visual disturbance. A subsequent MRI Scan demonstrated ischaemic
      changes in the territory of his right posterior cerebral artery. Transthoracic
      echocardiography was normal but a bubble contrast study was strongly positive
      indicating the presence of a relatively large patent foramen ovale (PFO). He
      underwent endovascular closure of his patent foramen ovale and was subsequently
      upgraded back to full duties. A 35-year-old Army Sergeant presented with sudden
      onset collapse, right sided weakness, dysarthria and confusion. He was airlifted
      to a Host Nation hospital and following a normal CT head underwent thrombolysis
      in the Emergency Department. This was unsuccessful but a CT guided embolectomy
      led to complete resolution of symptoms. Subsequent transthoracic echo revealed a
      PFO. He underwent endovascular closure and has since been returned to full
      duties. The incidence of PFO is common affecting 27% of the population but the
      incidence of ischaemic stroke in young adults (aged 15-45 years old) is rare.
      This maybe linked to the size of the PFOs in symptomatic individuals. These case
      reports emphasise the requirement for further investigation of individuals
      presenting with collapse and persisting neurology. Differential diagnosis and
      initial management for primary care and pre-hospital clinicians is also reviewed.

PMID- 22970642
TI  - Surgical training in Camp Bastion, Afghanistan.
AB  - INTRODUCTION: Surgical trauma care on operations is delivered by consultants. The
      DMS presently delivers training to surgeons to enable them to deliver this care
      as newly-qualified consultants. Deploying as a trainee is one of many training
      evolutions available to achieve this competency. This paper describes the process
      involved in trainees deploying, and the training received by the first author
      (CAF) during a recent deployment. METHODS: Pre-deployment training and the
      process for gaining recognition of training time by the GMC are described. All
      surgical procedures performed by the first author were recorded prospectively,
      together with the level of supervision. RESULTS: The first author performed 210
      procedures in 124 operations on 87 patients in a seven week deployment. This was
      prospectively recognised for training by the GMC. All procedures were supervised
      by consultant trainers. Procedures included trauma surgical procedures and those
      under the specialties of Plastic Surgery, Orthopaedic Surgery and General
      Surgery. CONCLUSIONS: Deploying on operations as a trainee is invaluable in
      preparing DMS juniors for their future roles as consultants in the DMS. Training
      is received not only in a breadth of surgical and resuscitative procedures,
      beyond a trainee's "base specialty", but also in other critical aspects of
      deployments including Crew Resource Management.

PMID- 22970643
TI  - Delay in diagnosis of neck of femur stress fracture in a female military recruit.
AB  - We report the delay in diagnosis of a Neck of Femur (NOF) stress fracture in
      mixed sex basic military training. Stress fractures are common in military
      training with the incidence reported as ranging between 3.2-31%. NOF stress
      fractures, whilst only representing around 8% of stress fractures are associated
      with a high morbidity. It is imperative that medical officers looking after
      military recruits have a sound knowledge of the potential signs, symptoms and
      presentation of these injuries. Medical officers should always remains vigilant
      for stress fractures especially in mixed military training.

PMID- 22970644
TI  - Hyperbaric medicine unit, past, present and future.

PMID- 22970645
TI  - Working with Royal Fleet Auxilary.

PMID- 22970646
TI  - The Royal Hospital Haslar: from lind to the 21st century.

PMID- 22970647
TI  - The Harvey-Fletcher medal and prize.

PMID- 22970648
TI  - Estimated pregnancy rates and rates of pregnancy outcomes for the United States,
      1990-2008.
AB  - OBJECTIVES: This report presents detailed pregnancy rates for 1990-2008, updating
      a national series of rates extending since 1976. METHODS: Tabular and graphical
      data on pregnancy rates by age, race, and Hispanic origin, and by marital status
      are presented and described. RESULTS: In 2008, an estimated 6,578,000 pregnancies
      resulted in 4,248,000 live births, 1,212,000 induced abortions, and 1,118,000
      fetal losses. The 2008 pregnancy rate of 105.5 pregnancies per 1000 women aged 15
      44 is 9 percent below the 1990 peak of 115.8. The teen pregnancy rate dropped 40
      percent from 1990 to 2008, reaching a historic low of 69.8 per 1000 women aged 15
      19. Pregnancy rates have declined significantly for non-Hispanic white, non
      Hispanic black, and Hispanic teenagers. Rates in 2008 for non-Hispanic black and
      Hispanic teenagers were two to three times higher than the rates for non-Hispanic
      white teenagers. Pregnancy rates for women in their early 20s declined to the
      lowest level in more than three decades, although the declines have been more
      modest than for teenagers. Pregnancy rates for women aged 25-29 have changed
      relatively little since 1990, while rates for women in their 30s and early 40s
      increased.

PMID- 22970649
TI  - Ab initio prediction of adsorption isotherms for small molecules in metal-organic
      frameworks: the effect of lateral interactions for methane/CPO-27-Mg.
AB  - A hybrid method that combines density functional theory for periodic structures
      with wave function-based electron correlation methods for finite-size models of
      adsorption sites is employed to calculate energies for adsorption of CH(4) onto
      different sites in the metal-organic framework (MOF) CPO-27-Mg (Mg-MOF-74) with
      chemical accuracy. The adsorption energies for the Mg(2+), linker, second layer
      sites are -27.8, -18.3, and -15.1 kJ/mol. Adsorbate-adsorbate interactions
      increase the average CH(4) adsorption energy by about 10% (2.4 kJ/mol). The free
      rotor-harmonic oscillator-ideal gas model is applied to calculate free
      energies/equilibrium constants for adsorption on the individual sites. This
      information is used in a multisite Langmuir model, augmented with a Bragg
      Williams model for lateral interactions, to calculate adsorption isotherms. This
      ab initio approach yields the contributions of the individual sites to the final
      isotherms and also of the lateral interactions that contribute about 15% to the
      maximum excess adsorption capacity. Isotherms are calculated for both absolute
      amounts, for calculation of isosteric heats of adsorption as function of
      coverage, and excess amounts, for comparison with measured isotherms. Agreement
      with observed excess isotherms is reached if the experimentally determined
      limited accessibility of adsorption sites (78%) is taken into account.

PMID- 22970651
TI  - Synthesis and characterization of hexagonal boron nitride film as a dielectric
      layer for graphene devices.
AB  - Hexagonal boron nitride (h-BN) is a promising material as a dielectric layer or
      substrate for two-dimensional electronic devices. In this work, we report the
      synthesis of large-area h-BN film using atmospheric pressure chemical vapor
      deposition on a copper foil, followed by Cu etching and transfer to a target
      substrate. The growth rate of h-BN film at a constant temperature is strongly
      affected by the concentration of borazine as a precursor and the ambient gas
      condition such as the ratio of hydrogen and nitrogen. h-BN films with different
      thicknesses can be achieved by controlling the growth time or tuning the growth
      conditions. Transmission electron microscope characterization reveals that these
      h-BN films are polycrystalline, and the c-axis of the crystallites points to
      different directions. The stoichiometry ratio of boron and nitrogen is close to
      1:1, obtained by electron energy loss spectroscopy. The dielectric constant of h
      BN film obtained by parallel capacitance measurements (25 MUm(2) large areas) is
      2-4. These CVD-grown h-BN films were integrated as a dielectric layer in top
      gated CVD graphene devices, and the mobility of the CVD graphene device (in the
      few thousands cm(2)/(V.s) range) remains the same before and after device
      integration.

PMID- 22970650
TI  - Glyoxylate carboligase: a unique thiamin diphosphate-dependent enzyme that can
      cycle between the 4'-aminopyrimidinium and 1',4'-iminopyrimidine tautomeric forms
      in the absence of the conserved glutamate.
AB  - Glyoxylate carboligase (GCL) is a thiamin diphosphate (ThDP)-dependent enzyme,
      which catalyzes the decarboxylation of glyoxylate and ligation to a second
      molecule of glyoxylate to form tartronate semialdehyde (TSA). This enzyme is
      unique among ThDP enzymes in that it lacks a conserved glutamate near the N1'
      atom of ThDP (replaced by Val51) or any other potential acid-base side chains
      near ThDP. The V51D substitution shifts the pH optimum to 6.0-6.2 (pK(a) of 6.2)
      for TSA formation from pH 7.0-7.7 in wild-type GCL. This pK(a) is similar to the
      pK(a) of 6.1 for the 1',4'-iminopyrimidine (IP)-4'-aminopyrimidinium (APH(+))
      protonic equilibrium, suggesting that the same groups control both ThDP
      protonation and TSA formation. The key covalent ThDP-bound intermediates were
      identified on V51D GCL by a combination of steady-state and stopped-flow circular
      dichroism methods, yielding rate constants for their formation and decomposition.
      It was demonstrated that active center variants with substitution at I393 could
      synthesize (S)-acetolactate from pyruvate solely, and acetylglycolate derived
      from pyruvate as the acetyl donor and glyoxylate as the acceptor, implying that
      this substitutent favored pyruvate as the donor in carboligase reactions.
      Consistent with these observations, the I393A GLC variants could stabilize the
      predecarboxylation intermediate analogues derived from acetylphosphinate,
      propionylphosphinate, and methyl acetylphosphonate in their IP tautomeric forms
      notwithstanding the absence of the conserved glutamate. The role of the residue
      at the position occupied typically by the conserved Glu controls the pH
      dependence of kinetic parameters, while the entire reaction sequence could be
      catalyzed by ThDP itself, once the APH(+) form is accessible.

PMID- 22970652
TI  - Influences of four different light-emitting diode lights on flowering and
      polyphenol variations in the leaves of chrysanthemum (Chrysanthemum morifolium).
AB  - Light-emitting diodes (LEDs) are an efficient alternative to traditional lamps
      for plant growth. To investigate the influence of LEDs on flowering and
      polyphenol biosynthesis in the leaves of chrysanthemum, the plants were grown
      under supplemental blue, green, red, and white LEDs. Flower budding was formed
      even after a longer photoperiod than a critical day length of 13.5 h per day
      under blue light illumination. The weights of leaves and stems were highest under
      the white light illumination growth condition, whereas the weight of roots
      appeared to be independent of light quality. Among nine polyphenols characterized
      by high-performance liquid chromatography-tandem mass spectroscopy, three
      polyphenols were identified for the first time in chrysanthemum. A quantitation
      and principal component analysis biplot demonstrated that luteolin-7-O-glucoside
      (2), luteolin-7-O-glucuronide (3), and quercetagetin-trimethyl ether (8) were the
      highest polyphenols yielded under green light, and dicaffeoylquinic acid isomer
      (4), dicaffeoylquinic acid isomer (5), naringenin (7), and apigenin-7-O
      glucuronide (6) were greatest under red light. Chlorogenic acid (1) and 1,2,6
      trihydroxy-7,8-dimethoxy-3-methylanthraquinone (9) were produced in similar
      concentrations under both light types. The white and blue light appeared
      inefficient for polyphenol production. Taken together, our results suggest that
      the chrysanthemum flowering and polyphenol production are influenced by light
      quality composition.

PMID- 22970653
TI  - Comparison of orthogonality estimation methods for the two-dimensional
      separations of peptides.
AB  - In two-dimensional chromatography, the orthogonality of separation is important
      for achieving high peak capacity. In this paper, a number of different metrics
      are compared as measures of orthogonality. Six peptide elution data sets acquired
      on different stationary phases are plotted against reversed phase retention data
      and examined as two-dimensional chromatographic pairs. The data, including six in
      silico prepared data pairs, are utilized to challenge and compare selected
      orthogonality metrics. The metrics include correlation coefficients, mutual
      information, box-counting dimensionality, and surface fractional coverage with
      different hulls. Although correlation coefficients were found to be less suited
      for the intended purpose, other methods can provide a suitable measure of
      orthogonality. The presented results are discussed in terms of method utility,
      simplicity, and applicability for statistically small sets of chromatographic
      data. Two of the methods, box counting dimensionality and fractional coverage,
      were found to be mathematically related.

PMID- 22970654
TI  - Impact of different synthetic bone fillers on healing of extraction sockets: an
      experimental study in dogs.
AB  - OBJECTIVES: The objective of this study was to elucidate the socket healing
      process and biodegradation of incorporating synthetic bone fillers followed by
      grafting of the fresh extraction socket. MATERIALS AND METHODS: Third premolars
      in four quadrants of eight beagle dogs were extracted and randomly treated with
      either one of hydroxyapatite (HA), biphasic calcium phosphate (BCP), beta
      tricalcium phosphate (beta-TCP), or no graft (C). Histologic observations and
      histomorphometric analysis at three zones (apical, middle, and coronal) of the
      socket were performed. Socket area (S) and the proportions of newly formed bone
      (%NB), residual biomaterials (%RB), and fibrovascular connective tissue (%FCT) at
      2, 4, and 8 weeks were measured. The numbers of osteoclast-like multinucleated
      cells (No.OC) were also determined at the three zones. RESULTS: %NB was
      significantly higher in control group compared with the grafted groups at all
      healing periods. %NB of HA and BCP increased with time, whereas %RB showed
      different patterns that decreased in BCP, unlike the minimal change observed in
      HA. %NB of beta-TCP showed smallest portion compared with other grafted groups at
      2 and 4 weeks, however, significantly increased at 8 weeks. %RB of beta-TCP was
      less than HA and BCP at all healing periods. Numbers of multinucleated cells were
      greater in BCP and beta-TCP, followed by HA and smallest in control group.
      CONCLUSIONS: Within the limit of this study, bone formation of the extraction
      socket was delayed in the sockets grafted with synthetic bone fillers and showed
      different healing process according to the biodegradation patterns.

PMID- 22970655
TI  - Photobiomodulation in dentistry.

PMID- 22970656
TI  - Dental health and oral health-related quality of life in children with congenital
      bleeding disorders.
AB  - The purpose of this study was to investigate the dental and some other aspects of
      oral health status of young patients with congenital bleeding disorders (CBD) and
      the impact of these on their quality of life (OHR-QoL) compared with controls.
      DMFS-dmfs (Decayed, Missed, Filled Tooth surfaces in permanent and primary teeth)
      scores, Simplified oral hygiene index, occurance of hypoplasia of first permanent
      molars, Temporomandibular joint dysfunction and occlusion of 46 CBD patients at
      the age range of 2-15 years and 46 of other children as control were compared,
      and the impact of their oral health situation on quality of life was also
      investigated. Data were analysed by chi-square, t-test and Pearson correlation.
      Patients were significantly more caries-free with less decayed teeth in primary
      permanent dentition (P = 0.03, t = -2.17).The mean scores of OHR-QoL of CBD
      patients and controls were not significantly different. Oral Bleeding was the
      significant variable in relation to 'oral health-related quality of life' in CBD
      groups (Pearson correlation, r = -0.56, P = 0.000). OHR-QoL in the control group
      was related to dmfs score (r = -0.392, P = 0.011) and male gender (r = -0.329, P
      = 0.026). Congenital bleeding disorder CBD patients were found to have a better
      dental health situation in primary dentition compared with controls; however,
      their 'oral health-related quality of life' was similar. Oral bleeding was the
      only significant factor related to OHR-QoL in CBD. It shows an overall importance
      of development of comprehensive care centres for CBD as the main cause of this
      achievement.

PMID- 22970657
TI  - Feasibility and safety of functional cholecystectomy by pure NOTES: a pilot
      animal study.
AB  - BACKGROUND: NOTES cholecystectomy has become one of the hottest areas of
      research. But most of the cases need the assistance of the laparoscope. This
      study is conducted to evaluate the feasibility and safety of a newly proposed
      operative method-functional cholecystectomy by pure NOTES. MATERIALS AND METHODS:
      The functional cholecystectomy was performed on eight female miniature pigs. An
      incision was made on the vaginal wall, and an endoscope was inserted into the
      peritoneal cavity to create a pneumoperitoneum to expose the intra-abdominal
      viscera, gallbladder, and cystic duct. The cystic duct was isolated and closed
      with a clip. Then, an injection needle was inserted into the gallbladder to suck
      up the bile. After the gallbladder was washed with saline, an incision was made
      on the wall of the gallbladder, and the tip of the endoscope was inserted into
      the gallbladder cavity. After the endoscope was withdrawn, the gallbladder
      incision was closed with clips in four pigs and was suspended in the other four
      pigs. The vaginal incision was closed with clips. All the animals were closely
      monitored and euthanized 28 days after the procedure. Necropsy was performed.
      RESULTS: The functional cholecystectomy was successfully completed in all eight
      pigs. No severe intraoperative complications occurred. The animals recovered well
      postoperatively. At necropsy, no macroscopic signs of intraperitoneal infection
      or bile leakage in the peritoneal cavity were observed, and the clips were still
      present on the cystic duct in a good position in all cases. The gallbladder
      incision healed, with no sign of bile leakage or injury to the adjacent organs.
      CONCLUSIONS: We successfully performed the functional cholecystectomy by
      transvaginal approach on pigs, which appears to be feasible, safe, and
      convenient. Functional cholecystectomy provides a new fitting path to pure NOTES.

PMID- 22970658
TI  - Efficacy and safety of flupirtine modified release for the management of moderate
      to severe chronic low back pain: results of SUPREME, a prospective randomized,
      double-blind, placebo- and active-controlled parallel-group phase IV study.
AB  - OBJECTIVE: To demonstrate non-inferior/superior efficacy of flupirtine modified
      release (MR) compared with tramadol/placebo for the management of moderate to
      severe chronic low back pain (LBP). RESEARCH DESIGN: Randomized, double-blind,
      active-/placebo-controlled double-dummy multicenter study, performed in 31 German
      study centers. LBP patients (n = 363) with moderate pain intensity were
      randomized 1:1:1 to receive flupirtine MR 400 mg, tramadol extended release (ER)
      200 mg, or matching placebo (each given OD in the evening) over 4 weeks. CLINICAL
      TRIAL REGISTRATION: EudraCT 2009-013268-38. MAIN OUTCOME MEASURES: Primary
      endpoint was change from baseline in the LBP intensity index (LBPIX; 11-point
      NRS) at week 4; last observation carried forward was used to impute missing
      scores. RESULTS: Least square (LS) mean +/- SD LBPIX changes from baseline at
      week 4 were clinically significant for all three treatment groups of the intent
      to-treat (ITT) and the per-protocol (PP) population (n = 326/276): placebo (n =
      110/96): -1.81 +/- 1.65/-1.77 +/- 1.59; flupirtine MR (n = 109/95): -2.23 +/-
      1.73/-2.28 +/- 1.68; and tramadol ER (n = 107/85): -1.92 +/- 1.84/2.03 +/- 1.83
      (p < 0.001 for each). ITT/PP treatment effects for flupirtine MR were non
      inferior when compared with tramadol ER and superior when compared with placebo
      (p = 0.003/0.033). Significantly more ITT patients treated with flupirtine MR
      (59.6/37.6 showed a >=30/50% LBPIX relief in comparison to placebo (46.4/24.6%; p
      vs. flupirtine MR: 0.049/0.037). Treatment contrasts for tramadol failed to reach
      significance vs. placebo. Within the safety population (n = 355), flupirtine MR
      (n = 119) was associated with a significantly lower incidence of treatment
      emergent AEs (TEAEs; 21.0%) and TEAE-related study discontinuations (3.4%) than
      tramadol ER (n = 116; 34.5/12.0%; p = 0.039/0.017) and exhibited an overall
      safety/tolerability profile non-inferior to placebo (n = 120; 15.8/3.3%; p = ns
      for each). Major limitations of this study were the short treatment duration, the
      comparison of different drug classes and the lack of a titration phase.
      CONCLUSIONS: The analgesic efficacy of flupirtine MR 400 mg OD was comparable to
      that of tramadol ER 200 mg OD and superior to that of placebo.

PMID- 22970659
TI  - Smoking influences response to inhaled corticosteroids in patients with asthma: a
      meta-analysis.
AB  - OBJECTIVE: To determine the effects of smoking on efficacy of inhaled
      corticosteroids in asthmatics. RESEARCH DESIGN AND METHODS:
      Prospective/retrospective, controlled studies published up to May 2012 in smokers
      versus non-smokers with asthma using inhaled corticosteroids (ICSs) were
      retrieved from PubMed, Highwire and Embase databases. MAIN OUTCOME MEASURES: The
      primary outcomes were pulmonary function parameters [FEV(1) (forced expiratory
      volume in 1 second), a.m. PEF (a.m. peak expiratory flow) and p.m. PEF (p.m. peak
      expiratory flow)]. Secondary outcomes included differential eosinophil counts in
      sputum and peripheral blood, asthma control questionnaire-5 (ACQ-5) and
      concomitant use of medication. Pooled SMDs (standardized mean differences) were
      estimated by using a random-effect model and a fixed-effect model based on
      between-study heterogeneity. RESULTS: Of 242 studies identified, ten (N = 4070)
      met the inclusion criteria (seven of budesonide-based interventions, two of
      fluticasone and one unknown ICS trial). Both smokers and non-smokers were similar
      in age and baseline FEV(1). Smoking yielded considerably reduced mean change in
      FEV(1) [SMD = -0.197, 95% CI: (-0.327, -0.066), p = 0.003], morning PEF [SMD = 
      0.796, 95% CI: (-1.047, -0.545), p < 0.001], night-time PEF [SMD = -0.501, 95%
      CI: (-0.797, -0.204), p = 0.001] and post-treatment FEV(1) [SMD = -0.178, 95% CI:
      (-0.309, -0.046), p = 0.008] and increased use of concomitant medications [SMD =
      0.537, 95% CI: (0.166, 0.908), p = 0.005] in smokers, but not non-smokers with
      asthma, although there was no statistical difference in allergy-related endpoints
      and asthma score (ACQ-5). CONCLUSION: Smoking is associated with attenuated
      response to inhaled corticosteroids in asthmatics. This offers a rationale for
      persuasion of smoking cessation. Treatment outcomes might be improved by smoking
      cessation leading to improved lung function and ameliorated symptoms.

PMID- 22970660
TI  - Association between an IL-28B genetic polymorphism and the efficacy of the
      response-guided pegylated interferon therapy in children with chronic hepatic C
      infection.
AB  - AIM: The relation between interleukin-28B (IL-28B) genotypes and treatment
      induced hepatitis C virus (HCV) clearance in children is unknown. This was a
      retrospective study to evaluate the association between an IL-28B genotype
      (rs8099917) and pegylated (PEG) interferon (IFN) response. METHODS: Sixty-three
      children (median age, 7 years; range, 3-17 years; 22 with HCV genotype 1 and 41
      with genotype non-1) with chronic HCV infection who were treated with response
      guided PEG IFN on the basis of viral load were evaluated. RESULTS: The duration
      of treatment with PEG IFN was 24 weeks in one child (2%), 36 weeks in eight
      children (13%), 48 weeks in 36 children (57%), 60 weeks in 11 children (17%) and
      72 weeks in seven children (11%). Of the total 63 children, 54 (86%) were
      initially treated with PEG IFN-alpha-2a monotherapy. The remaining nine (14%)
      received PEG IFN plus ribavirin as the initial therapy. Of the 54 children
      initially treated with monotherapy, 35 (65%) continued receiving monotherapy
      until the end of treatment. In the remaining 19 (35%), monotherapy was changed to
      PEG IFN plus ribavirin at 12 or 24 weeks of treatment. Of the total 63 children,
      54 (86%) achieved a sustained virological response (SVR). In univariate analysis,
      rs8099917 genotype TT (P = 0.075) showed a weak association with SVR. However,
      the multivariate analysis revealed no predictive factors which had a significant
      association with SVR. CONCLUSION: The IL-28B genotype was not a strong
      pretreatment predictor for SVR in a mixed genotype cohort of children treated
      with response-guided PEG IFN therapy.

PMID- 22970661
TI  - The neonate: a community's moral compass?

PMID- 22970663
TI  - Do antenatal classes do enough to prepare parents for when things go wrong?
AB  - Antenatal classes play an important role in educating expectant parents about
      pregnancy, labour and delivery. They cover a range of topics, but they are
      failing parents because they do not provide sufficient information to prepare
      them for abnormal labours and deliveries. They do not do enough to educate
      parents about what to expect when problems arise and what happens afterwards.
      This paper looks at whether classes do enough to make parents aware of problems
      and whether they should be doing more. It examines the arguments both for and
      against including this information in antenatal classes.

PMID- 22970664
TI  - Controversies in neonatal infection.

PMID- 22970665
TI  - Developmental origins of health and adult disease: what should
      neonatologists/paediatricians be considering about the long-term health of their
      patients?
AB  - The developmental origins of health and disease hypothesis is now strongly
      supported by both animal and human evidence, and as a consequence, obstetricians,
      neonatologists and paediatricians need to consider the impact that the in utero
      and early post-natal environment can have on later renal, cardiovascular and
      metabolic health. Four common clinical scenarios were provided along with animal
      and human evidence identifying long-term health implications. Suggestions as to
      how we should translate this growing body of evidence into practice are provided.

PMID- 22970666
TI  - Turn and face the strange - ch..ch..ch..changes to neonatal resuscitation
      guidelines in the past decade.
AB  - Resuscitation of newborns has been described since ancient times and is among the
      most commonly performed emergency medical interventions. The International
      Liaison Committee on Resuscitation first made recommendations on resuscitation in
      newborns in 1999. Over the last decade, new research and careful review of the
      available evidence have resulted in substantial changes to these recommendations 
      in particular, regarding the assessment of colour, giving supplemental oxygen,
      suctioning infants born through meconium-stained liquor, confirming endotracheal
      tube position, the use of pulse oximetry, giving CPAP to premature infants,
      keeping preterm infants warm using polyethylene wrapping and cooling term infants
      with encephalopathy. This process has also highlighted the paucity of evidence to
      support much of the care given to infants in the delivery room and the need for
      research to refine our techniques.

PMID- 22970667
TI  - Lung protective ventilation in extremely preterm infants.
AB  - The lungs of an extremely preterm infant <=28 weeks gestation are structurally
      and biochemically immature and vulnerable to injury from positive pressure
      ventilation. A lung protective approach to respiratory support is vital, aiming
      to ventilate an open lung, using the lowest pressure settings that maintain
      recruitment and oxygenation and avoiding hyperinflation with each tidal breath.
      For infants with severe respiratory distress syndrome and persistent atelectasis,
      lung protective ventilation requires recruitment using stepwise pressure
      increments, followed by reduction in ventilator pressures in search of an optimal
      point at which to maintain ventilation. Several studies, including a single
      randomised controlled trial, have found this lung protective strategy to be more
      effectively administered using high-frequency oscillatory ventilation rather than
      conventional ventilation. Many extremely preterm infants have minimal atelectasis
      and low oxygen requirements in the first days of life, and the ventilatory
      approach in this case should be one of avoidance of factors including
      overdistension that are known to contribute to later pulmonary deterioration.
      From a practical perspective, this means setting positive end-expiratory pressure
      at the lowest value that maintains oxygenation and restricting tidal volume using
      a volume-targeted mode of ventilation.

PMID- 22970668
TI  - Nasal continuous positive airway pressure for respiratory distress in non
      tertiary care centres: what is needed and where to from here?
AB  - Respiratory distress is one of the commonest reasons for admission to a special
      care nursery (SCN) affecting between 2.5 and 5.0% of all babies born per year.
      While most recover with supplemental oxygen, some require transfer to a neonatal
      intensive care leading to significant family disruption, and financial cost. Does
      nasal continuous positive airway pressure (nCPAP) improve outcomes in babies with
      respiratory distress? What are the risks of its use? Should it be used in SCNs,
      and, if so, what is required in order to undertake nCPAP safely? There is strong
      evidence to support the use of nCPAP in the treatment of babies with respiratory
      distress. The risk benefit ratio of providing nCPAP in SCNs depends upon many
      factors including the ability to maintain the skills required and the
      distance/time to the nearest tertiary centre. Appropriate nurseries should be
      identified with the aim of supporting them in the provision of nCPAP in a safe
      manner.

PMID- 22970669
TI  - Preterm patent ductus arteriosus: should we treat it?
AB  - Debate about the importance of the preterm patent ductus arteriosus (PDA) remains
      unresolved. Ultrasound studies of PDA have suggested that the haemodynamic impact
      may be much earlier after birth than previously thought, but we still do not know
      when to treat a PDA. Studies that have tested symptomatic or pre-symptomatic
      treatment are mainly historical and have not tested the effect of no treatment.
      Prophylactic treatment is the best studied regimen, but improvements in some
      short-term outcomes do not translate to any difference in longer term outcomes.
      Neonatologists have been reluctant to engage in trials that test treatment
      against not treating at all or very rarely. Targeting treatment on the basis of
      the early post-natal constrictive response of the duct is currently being tested
      as a possible strategy.

PMID- 22970670
TI  - Growth monitoring of low birthweight infants: what references to use?
AB  - Growth charts are the mainstay of monitoring growth in babies who were born small
      or preterm. A variety of different charts are available, each with specific
      limitations. Most birthweight centile charts underestimate growth restriction in
      preterm babies and there are few good charts for monitoring longitudinal growth
      in preterm babies; it is important to be aware of the limitations of using cross
      sectional data for monitoring longitudinal growth. Customised centile charts of
      fetal growth are used increasingly for antenatal monitoring for small-for
      gestational age fetuses despite a lack of robust evidence. It is also unclear
      whether customised centile charts should be used for assessing birthweight,
      particularly in babies born at term. Faltering post-natal growth in preterm
      babies is very common but need not be universal with close attention to
      nutrition. Monitoring of growth trajectories through infancy following either
      fetal growth restriction or post-natal faltering growth is important to ensure
      proportional growth, particularly during periods of accelerated growth. This
      review will discuss these issues in the context of current practice in Australia
      and New Zealand.

PMID- 22970671
TI  - Infant formulas for preterm infants: in-hospital and post-discharge.
AB  - The availability and composition of preterm and post-discharge formulas (PDFs)
      have undergone considerable changes over the last decade. Human milk,
      supplemented with multi-component fortifier, is the preferred feed for very
      preterm infants as it has beneficial effects for both short- and long-term
      outcomes compared with formula. If supply of mother's milk or donor milk is
      inadequate, a breast milk substitute specifically designed for premature infants
      is the next option. Preterm formula is intended to provide nutrient intakes to
      match intrauterine growth and nutrient accretion rates and is enriched with
      energy, macronutrients, minerals, vitamins, and trace elements compared with term
      infant formulas. Post-natal longitudinal growth failure has been reported almost
      universally in extremely preterm infants. Since 2009, a nutritionally enriched
      PDF specifically designed for preterm infants post hospital discharge with
      faltering growth has been available in Australia and New Zealand. This formula is
      an intermediary between preterm and term formulas and contains more energy (73
      kcal/100 mL), protein (1.9 g/100 mL), minerals, vitamins, and trace elements than
      term formulas. Although the use of a PDF is based on sound nutritional knowledge,
      the 2012 Cochrane Systematic Review of 10 trials comparing feeding preterm
      infants with PDF and term formula did not demonstrate any short- or long-term
      benefits. Health professionals need to make individual decisions on whether and
      how to use PDF.

PMID- 22970672
TI  - Increasing rates of prematurity and epidemiology of late preterm birth.
AB  - Preterm birth rates in Australia have risen in the last two decades, mostly
      accounted for by the rise in late preterm births. Late preterm births (34-36
      weeks) comprise 70% of all preterm births, which translates to approximately
      16,000 births annually in Australia. The precise causes for this trend are
      unclear; however, possible aetiologies include increasing maternal age, increased
      use of artificial reproductive technologies and increased multiple births.
      Compared with term-born children, late preterm children not only have increased
      mortality and in-hospital morbidity including respiratory difficulties, but also
      long-term cognitive, school performance, behaviour and psychiatric problems. The
      potential public health and educational burden of late preterm birth is
      considerable. More research is required in this area to understand the risk
      factors for late preterm birth and to help identify those children at highest
      risk of developmental deficits.

PMID- 22970673
TI  - Which high-risk infants should we follow-up and how should we do it?
AB  - Early detection of neurodevelopmental delay and appropriate intervention has been
      associated with improved academic and social outcomes. Identifying those who are
      at high risk and might benefit is not straightforward. Approximately 2% of
      infants are admitted to a neonatal intensive care unit after birth and these
      babies are known to be at high risk of developmental impairment. While it is well
      recognised that the extreme preterm infant is at high risk of developmental
      impairment, there is increasing evidence of a risk in late preterm infants as
      well as those undergoing major cardiac and non-cardiac surgery. Not all infants
      are enrolled in multidisciplinary follow-up clinics with easy access to early
      intervention. These clinics are expensive to run with both limited and
      conflicting data on their long-term value. This review will concentrate on
      identifying which infants are at risk, reviewing the aetiology of the risk
      factors and the efficacy of follow-up clinics.

PMID- 22970674
TI  - Magnetic resonance imaging of the brain at term equivalent age in extremely
      premature neonates: to scan or not to scan?
AB  - In the last decade, the role of magnetic resonance imaging (MRI) in neonatal care
      for prematurely born infants has rapidly expanded and evolved. Recent
      investigations addressed many of the practical issues pertaining to image
      acquisition and interpretation, enabling high-quality MR images to be obtained
      without sedating medications in preterm infants at any institution. Expanded
      application has demonstrated that MRI provides superior ability to assess
      cerebral development and identify and define cerebral injury in comparison to
      other imaging modalities. Term equivalent MRI results have been shown to
      correlate with neurodevelopmental outcomes, providing improved predictive ability
      over other neuroimaging, clinical or physical examination measures. Regular
      utilisation of MRI in this population is fundamental to gaining the knowledge and
      expertise necessary for rational, accurate application. Ongoing experiences will
      continue to shape the nature and type of information available to clinicians and
      families using MRI, further refining its role as a routine element of neonatal
      care.

PMID- 22970675
TI  - Review of neonatal alloimmune thrombocytopenia.
AB  - Neonatal alloimmune thrombocytopenia (NAIT), with an incidence of one in 1000
      live births, is the most common cause of severe thrombocytopenia and intra
      cerebral haemorrhage in term neonates. NAIT results from trans-placental passage
      of maternal antibodies against a paternally derived fetal platelet alloantigen.
      Clinical presentation varies from unexpected thrombocytopenia on a blood film in
      a well newborn to intracranial haemorrhage (ICH). In contrast to haemolytic
      disease of the newborn, NAIT can present in a first pregnancy, and subsequent
      pregnancies are usually more severely affected. The role of antenatal screening
      for maternal alloantibodies instead of fetal blood sampling to identify at-risk
      fetuses remains uncertain, but there is a trend towards less invasive maternally
      directed treatment for at-risk pregnancies. Neonatal management is aimed at
      preventing or limiting thrombocytopenic bleeding with transfusion of antigen
      matched platelets.

PMID- 22970676
TI  - Incorporating speech-language pathology within Australian neonatal intensive care
      units.
AB  - Working in neonatal intensive care units (NICU) is considered to be advanced
      practice for speech-language pathologists (SLPs) requiring post-graduate
      specialised education and ongoing clinical mentoring, not easily accessible
      within some countries such as Australia. This review investigated whether there
      was evidence to support SLPs as core NICU team members, rather than fleeting
      therapists. The review found that the roles and responsibilities of SLPs in NICUs
      included assessment and intervention of preterm infant communication, feeding and
      swallowing using a family-centred approach. This approach was respectful of the
      cultural and linguistic diversity of the parents and the particular expertise of
      other NICU team members. Whilst there has been a significant and promising
      increase in research with regard to SLP involvement with preterm infants
      (especially around feeding and swallowing assessment and specific treatments),
      the need for high-quality well-designed research is essential.

PMID- 22970677
TI  - Use of oxygen for delivery room neonatal resuscitation in non-tertiary Australian
      and New Zealand hospitals: a survey of current practices, opinions and equipment.
AB  - BACKGROUND: Delivery room resuscitation of hypoxic newborn infants with pure or
      100% oxygen causes oxidative toxicity and increases mortality. Current
      international resuscitation guidelines therefore recommend that oxygen be used
      judiciously. However, this requires staff education and special equipment that
      may not be available in non-tertiary maternity hospitals where the majority of
      births occur. AIM: To determine current attitudes, practices and available
      equipment for the use of air and blended oxygen for newborn delivery room
      resuscitation in non-tertiary maternity hospitals of Australia and New Zealand
      (ANZ). METHODS: Structured questionnaires sent by mail and e-mail after personal
      phone contact. A total of 203 eligible hospitals in ANZ were identified. A second
      mailing was conducted a month later for non-responders. RESPONDERS: Final
      response rate was 64% (n= 130: 70% physicians, 30% midwives). The majority (121,
      93%) of respondents were aware of Australian Resuscitation Council
      recommendations, but only one in five hospitals had the capacity to deliver
      blended oxygen and 38% used pulse oximeters at delivery. Only 24 (18.5%)
      hospitals had guidelines. Air would be used by 68 (57%) hospitals to resuscitate
      term infants compared to 35 (31%) for preterm infants. Most (111, 91%) advocated
      the use of blended oxygen despite the lack of facilities. CONCLUSION: Only one in
      five ANZ non-tertiary maternity hospitals had the capacity to resuscitate newborn
      infants with air or blended oxygen. Most are aware of current recommendations and
      agreed that the use of less oxygen would be beneficial for this purpose. Further
      study into the necessary infrastructure required to implement these guidelines
      are recommended.

PMID- 22970678
TI  - Breast milk banking: current opinion and practice in Australian neonatal
      intensive care units.
AB  - AIM: To find out the knowledge and attitudes of health-care professionals (HCPs)
      in Australian neonatal intensive care units (NICUs) towards breast milk banking
      (BMBg) and pasteurised donated breast milk (PDBM). METHODS: Cross-sectional
      structured survey of HCPs in all 25 NICUs in Australia. RESULTS: Response rate
      was 43.4% (n= 358 of 825). Participants included nurses and midwives (291, 81.3%)
      and the remainder were neonatologists and neonatal trainees (67, 18.7%). A
      variable number of HCPs agreed that PDBM would decrease the risk of necrotising
      enterocolitis (81%) and allergies (48.9%), 8.4% thought PDBM will carry risk of
      infections and 78.8% agreed that PDBM is preferable over formula, but only 67.5%
      thought that establishing breast milk banks (BMBs) are justifiable. Significant
      differences were found between doctors and nurses/midwives, with 19.4% of doctors
      compared with 5.8% of nurses/midwives agreed that PDBM carried an increased risk
      of infection. Although, over 90% of nurses/midwives and 70% of doctors agreed
      that the donation of breast milk is important, only 71% of nurses/midwives and
      52.2% of doctors thought that setting up a BMB was justifiable. CONCLUSION: The
      opinions about BMBg differ widely between HCPs; however, the majority support the
      practice. HCPs had different knowledge gaps in regard to BMBg. Nurses/midwives
      positively view the practice of BMBg more strongly compared with neonatologists.

PMID- 22970679
TI  - Role of breastfeeding in childhood cognitive development: a propensity score
      matching analysis.
AB  - AIM: To examine whether the association between breastfeeding and childhood
      cognitive development is direct or whether the association is spurious owing to
      confounding variables. METHOD: The current study conducted a propensity score
      matching (PSM) analysis using data from the Early Childhood Longitudinal Study,
      Birth Cohort. RESULTS:   The results of PSM models revealed that prior to
      matching, the association between breastfeeding and cognitive functioning was
      significant (mean difference = 3.20, t-value = 7.86, 95% confidence interval (CI)
      = 2.40-4.00, P <= 0.05). After controlling for a range of confounding factors,
      the mean difference was reduced by 40% (mean difference = 1.92, t-value = 3.75,
      95% CI = 0.92-2.93, P <= 0.05); however, significant differences remained between
      groups. CONCLUSION: The results produced in the current study provide tentative
      evidence that breastfeeding may have an influence on the development of cognitive
      abilities in children. Additional research is necessary, however, in order to
      further evaluate the causal impact and exact developmental pathway of
      breastfeeding on childhood cognitive growth.

PMID- 22970680
TI  - Chemoprophylaxis of neonatal fungal infections in very low birthweight infants:
      efficacy and safety of fluconazole and nystatin.
AB  - AIM: To review the use of antifungal chemoprophylaxis to prevent neonatal
      invasive fungal infections (IFI) in very low birthweight infants (VLBW <1500 g).
      METHOD: Systematic review of randomised controlled trials. RESULTS: Nine trials
      were identified (2029 infants), with six comparing fluconazole with placebo/no
      treatment (840 infants), three comparing nystatin with placebo/no treatment (1200
      infants) and two comparing fluconazole and nystatin (257 infants). Prophylactic
      fluconazole reduced the incidence of IFI in VLBW infants <1500 g to 5.1% compared
      with 16.0% in infants receiving placebo, relative risk (RR) = 0.36 (95%
      confidence interval 0.15-0.89). The mortality was 10.9% and 16.7%, respectively
      (RR 0.76, 0.54-1.08). Oral nystatin reduced the incidence of IFI in VLBW infants
      to 5.3% compared with 28.0% in infants receiving placebo (RR 0.16, 0.11-0.23).
      Mortality was 7.5% with nystatin and 10.9% with placebo (RR 0.86, 0.59-1.26). The
      incidence of IFI in studies comparing fluconazole and nystatin was 3.6% and 8.0%,
      respectively (RR 0.54, 0.19-1.56), and mortality was not significantly different:
      4.6% versus 9.8% (RR 0.43, 0-4.31) CONCLUSIONS: Prophylactic fluconazole and oral
      nystatin are both highly effective in preventing IFI in VLBW infants. Both agents
      are safe without significant toxicities. Antifungal prophylaxis should therefore
      be used in all VLBW infants. Given the paucity of data comparing fluconazole with
      nystatin, the choice of antifungal agent should be influenced by the incidence of
      IFI, local epidemiology and relative cost.

PMID- 22970681
TI  - Barriers to neonatal care in developing countries: parents' and providers'
      perceptions.
AB  - AIM: Hospital care and advanced medical technologies for sick neonates are
      increasingly available, but not always readily accessible, in many countries. We
      characterised parents' and providers' perceptions of barriers to neonatal care in
      developing countries. METHODS: We interviewed parents whose infant was
      hospitalised within the first month of life in Cambodia, Malaysia, Laos and
      Vietnam, asking about perceived barriers to obtaining newborn care. We also
      surveyed health-care providers about perceived barriers to providing care.
      RESULTS: We interviewed 198 parents and 212 newborn care providers (physicians,
      nurses, midwives, paediatric and nursing trainees). Most families paid all costs
      of newborn care, which they reported as a hardship. Although newborn care is
      accessible, 39% reported that hospitals are too distant; almost 20% did not know
      where to obtain care. Parents cited lack of cleanliness (46%), poor availability
      of medications (42%) or services (36%), staff friendliness (42%), poor infant
      outcome (45%), poor communications with staff (44%) and costs of care (34%) as
      significant problems during prior newborn care. Providers cited lack of equipment
      (74%), lack of staff training (61%) and poor infrastructure (51%) as barriers to
      providing neonatal care. Providers identified distance to hospital, lack of
      transportation, care costs and low parental education as barriers for families.
      CONCLUSIONS: Improving cleanliness, staff friendliness and communication with
      parents may diminish some barriers to neonatal care in developing countries.
      Costs of newborn care, hospital infrastructure, distance to hospital, staffing
      shortages, limited staff training and limited access to medications pose more
      difficult barriers to remedy.

PMID- 22970682
TI  - A fatal case of hypernatraemic dehydration in a neonate.
AB  - Problems with lactation can result in hypernatraemic dehydration in the neonate,
      with potentially severe adverse consequences. This is illustrated in this fatal
      case of a 10 day old neonate who presented with excessive hypernatraemic
      dehydration due to insufficient breast milk intake, resulting in cerebral sinus
      vein thrombosis with cerebral haemorrhage and infarction. Differential diagnosis
      included excessive sodium intake (through inappropriately mixed formula or house
      remedies or through hyperaldosteronism) and high water deficit (renal or
      gastrointestinal losses, nephrogenic or central diabetes insipidus), all of which
      were ruled out by specific investigations or history. No evidence was found for
      inborn error of metabolism. The dehydration in this baby, however, was
      accentuated by trans-epidermal water loss due to an ichthyosiform skin condition.
      This first ever reported Australian fatality from neonatal hypernatraemic
      dehydration supports the concern of health care professionals over rising
      incidences of this entity in exclusively breastfed infants, and should encourage
      endorsement of improved monitoring of weight loss in newborns and breastfeeding
      support for their mothers.

PMID- 22970683
TI  - A standardized diagnostic interview for hypoactive sexual desire disorder in
      women: standard operating procedure (SOP Part 2).
AB  - INTRODUCTION: Taking into account that Hypoactive Sexual Desire Disorder (HSDD)
      is a patient-reported symptom and that the disorder is in general the result of
      the interaction of biological and psychosocial factors (see part 1), it is
      necessary to provide healthcare professionals with an operating procedure that is
      patient centered and multidimensional. AIM: Describing a patient-centered and
      multidimensional standard procedure to diagnose and manage HSDD on a primary care
      level. METHODS: Review of the literature. Semistructured interview and
      description of process. RESULT.: The interactive process with the patient follows
      several steps: initiation, narrative of the patient to understand the individual
      profile of the disorder, differentiating questions, descriptive diagnosis,
      exploration of conditioning biomedical, individual psychological, interpersonal,
      and sociocultural factors (including biomedical examinations), establishment of a
      biopsychosocial comprehensive explanatory diagnosis, which can be summarized in a
      nine-field matrix. This matrix will serve as orientation for therapeutic
      interventions adapted to the individual person. These interventions should always
      be based on basic counseling as a basis of treatment. Then adapted to the
      individual condition specific hormonal treatments (mainly estrogen and
      testosterone alone or combined) can be used after exclusion of contraindications.
      In patients with predominant psychosocial factors contributing to HSDD individual
      or couple psychotherapy is indicated. Psychopharmacological drugs are in
      development and partially investigated and will add to the therapeutic
      possibilities in the future. CONCLUSION: This model can serve as an ideal basis
      for the approach to the female patient with HSDD. It can be adapted to the
      individual clinical setting.

PMID- 22970684
TI  - Changes in gene expression induced by aromatic amine drugs: testing the danger
      hypothesis.
AB  - Virtually all drugs that contain a primary aromatic amine are associated with a
      high incidence of idiosyncratic drug reactions (IDRs), suggesting that this
      functional group has biological effects that may be used as biomarkers to predict
      IDR risk. Most IDRs exhibit evidence of immune involvement and the ability of
      aromatic amines to form reactive metabolites and redox cycle may be responsible
      for initiation of an immune response through induction of cell stress, as
      postulated by the Danger Hypothesis. If true, danger signals could be biomarkers
      of IDR risk. A previous attempt to test the Danger Hypothesis found that
      sulfamethoxazole (SMX), the only aromatic amine tested, was also the only drug
      not associated with an increase of cell stress genes in mice. To ensure that
      these observations were not species-specific, and to determine biomarkers of IDR
      risk common to aromatic amines, rats were treated with SMX and two other aromatic
      amine drugs, dapsone (DDS) and aminoglutethimide (AMG), and hepatic gene
      expression was determined using microarrays. As in mice, SMX induced minimal gene
      changes in the rat, and none indicated cell stress, whereas DDS and AMG induced
      several changes including up-regulation of enzymes such as aldo-keto reductase,
      glutathione-S-transferase, and aldehyde dehydrogenase, which may represent danger
      signals. Early insulin-induced hepatic gene (Eiih) was up-regulated by all three
      drugs. Some mRNA changes were observed in the Keap-1-Nrf2-ARE pathway; however,
      the pattern was significantly different for each drug. Overall, the most salient
      finding was that the changes in the liver were minimal, even though aromatic
      amines cause a high incidence of IDRs. The liver generates a large number of
      reactive species; however, the ability of aromatic amines to be bioactivated by
      cells of the immune system may be why they cause a high incidence of IDRs.

PMID- 22970685
TI  - Structures and vibrational spectra of SO(n)(p-) sulfur oxides, MSO(n)(-) anions,
      and MSO(n), M2SO(n) salts in the gas phase (n = 1-3; p = 0-2; M = Li, Na, K). A
      density functional theory study.
AB  - This theoretical study focuses on geometries, vibrational spectra, charge
      distributions, electron affinities, and reaction energies for SO(n)(p-) anions
      and alkali salts MSO(n)(-), M(1,2)SO(n) in the gas phase (n = 1-3; p = 0-2; M =
      Li-K). Most of our data for compounds with the S oxidation states 0, 2, and 4 are
      new in the literature. The bulk of the results are obtained at the B3PW91 level,
      with CCSD(T)=FC calculations carried out for relative energy calibrations; the 6
      311+G(3df) basis set is used throughout. The formation of contact ion pairs is
      prevalent; they are of type: (i) M(+)(SO(n)(-)) for the pi-radicals MSO, MSO(2),
      MSO(3) of doublet multiplicity; (ii) (M(+))(2)(SO(n)(2-)) for M(2)SO, M(2)SO(2),
      M(2)SO(3) in their singlet ground states; and (iii) M(ns)(SO(n)(-)) for the
      radicals MSO(-), MSO(2)(-), MSO(3)(-) in their triplet states. When isolated in
      matrices, M(2)SO and M(2)SO(2) will facilitate the spectroscopic study of the
      little known SO(2-) and SO(2)(2-) ions. Divalent M(2)SO(n) salts, due to their
      large dipole moments, should be highly soluble in polar solvents, first
      dissociating into MSO(n)(-) + M(+) products. For MSO(3), bidentate coordination
      OS(O(2)M) is preferred over tridentate S(O(3)M) binding. We confirm that all
      MSO(2) molecules are planar, at variance with an ESR study assigning to NaSO(2) a
      nonplanar structure. This study partially support the assignment of an
      experimental frequency at 918.2 cm(-1) (932 cm(-1), calculated) to the
      antisymmetric nu(a)(SO) mode of the elusive sulfoxilate ion, SO(2)(2-). A
      definitive identification, however, would require to record the vibrational
      spectrum below 800 cm(-1) (apparently not done in the original work) because the
      missing symmetric nu(s)(SO) mode is here found to lie around 760 cm(-1),
      exhibiting high intensity in both IR and Raman spectra.

PMID- 22970686
TI  - Identification of tissue differentiation rates in a mechanobiological model of
      fracture healing.
AB  - As a basis for model-based analysis of the processes in secondary fracture
      healing, a dynamical model is presented that characterises the physiological
      status in the fracture area by the location-dependent composition of tissues.
      Five types of tissue are distinguished: connective tissue, cartilage, bone,
      haematoma and avascular bone. A rule base is given that describes dynamical
      tissue differentiation processes. The rules consider not only a mechanical
      stimulus but also osteogenic and a vasculative factors as biological stimuli.
      Within this model structure, it is possible, e.g., to distinguish intramembranous
      from endochondral ossification processes. An objective function is introduced to
      assess accordance between the model-based simulation results and reference
      healing stages. By minimising this objective function, relevant tissue
      differentiation rates can be determined. For a reference process of secondary
      fracture healing it could be shown that the intramembranous ossification rate of
      0.313%/day (from connective tissue to bone) is much smaller than the endochondral
      ossification rate of 1.136%/day (from cartilage to bone). In order to verify the
      model approach, it is transferred to simulate long bone distraction. Results show
      that healing patterns of bone distraction can be predicted. Using this method, it
      is possible to identify model parameters for individual subjects. This will allow
      a patient-specific analysis of tissue healing processes in future. 

PMID- 22970687
TI  - Irregular assimilation progress: reasons for setbacks in the context of
      linguistic therapy of evaluation.
AB  - The assimilation model suggests progress in psychotherapy follows an eight-stage
      sequence described by the Assimilation of Problematic Experiences Scale (APES).
      This study sought to reconcile this developmental stage model with the common but
      superficially contradictory clinical observation that therapeutic advances
      alternate with setbacks. Setbacks (n=466) were identified in therapy transcripts
      of two clients and classified using a preliminary nine-category list of possible
      alternative reasons for setbacks. Most of the setbacks involved switches among
      the multiple strands of a problem due to (a) therapists exceeding clients'
      therapeutic zone of proximal development, (b) therapists guiding clients to shift
      toward relatively problematic material (balance metaphor), or (c) spontaneous
      switches. Rather than contradicting the theory, this close examination of
      setbacks yielded elaborations of it.

PMID- 22970688
TI  - "Drugs on oxygen": an update and perspective on the role of cytochrome P450
      testing in pharmacology.
AB  - Low hit rates for lead compounds and high attrition remain a major problem for
      drug development. The reasons for compound failure range from poor
      pharmacokinetics to toxic metabolites and adverse drug interactions; all of which
      are frequently mediated by cytochrome P450-dependent monooxygenases (CYPs).
      However, despite some 30 years of assay development and refinement, CYP
      metabolism remains a critical issue during drug development. While current
      testing strategies succeed in characterizing single substance toxicity, they are
      challenged by practical issues such as assay standardization or complex scenarios
      such as multidrug usage. This editorial summarizes where we stand and highlights
      the major challenges we face with CYPs in drug development today. The article
      also tries to spell out the future direction of CYP testing. The latter will
      depend on the extended inclusion of polypharmacy into testing strategies, as well
      as on our capability to make use of upcoming complex in vitro test systems and
      their inclusion into tiered testing strategies.

PMID- 22970689
TI  - The psychosocial influence to habit using make-up of women aged 40 to 59 years
      menopausal Japanese women.
AB  - We conducted a survey to elucidate the psychosocial influence of menopausal
      symptoms on the habit of using make-up. This study included 420 Japanese women
      (age, 40-59 years) who were examined for the first time in a specialized women's
      outpatient clinic of our institution from June 2010 to September 2011. Using the
      Menopause-Specific Quality of Life questionnaire (MENQOL), we analysed the scores
      in relation to menopausal symptoms and whether and how frequently the subject
      used make-up (including foundation, lip rouge and eyebrow brushing). JMP version
      9.0 software was used to statistically analyse the data. Significant results were
      observed for psychosocial symptoms (P = 0.0002) but not for vasomotor symptoms.
      Psychosocial symptoms tended to be more severe in women with climacteric <5 years
      previously. Furthermore, the frequency of make-up use was positively correlated
      with menopausal symptoms (P = 0.0251). There were strong relationships between
      psychological symptoms and make-up use in menopausal women. Psychological
      condition and the frequency of make-up use were inversely correlated, especially
      in women with climacteric <5 years previously.

PMID- 22970691
TI  - Are accelerometers a useful tool for measuring disease activity in children with
      eczema? Validity, responsiveness to change, and acceptability of use in a
      clinical trial setting.
AB  - BACKGROUND: Actigraphy, which uses accelerometers to record movement, has been
      proposed as an objective method of itch assessment in eczema. Previous studies
      have found strong correlations with actigraphy and video surveillance, disease
      severity and biological markers in patients with eczema. OBJECTIVES: To assess
      the validity of accelerometer data, its responsiveness to change and the
      practicality and acceptability of accelerometers when used as an outcome measure
      in a clinical trial. METHODS: This study used data collected from 336
      participants of the Softened Water Eczema Trial (SWET). Accelerometer data were
      compared with three standardized scales: Six Area, Six Sign Atopic Dermatitis
      (SASSAD) severity score, Patient Oriented Eczema Measure (POEM) and Dermatitis
      Family Impact (DFI). Spearman's rank testing was used for correlations. RESULTS:
      Only 70% of trial participants had complete data, compared with 96% for the
      primary outcome (eczema severity - SASSAD). The convergent validity of
      accelerometer data with other measures of eczema severity was poor: correlation
      with SASSAD 0.15 (P = 0.02) and POEM 0.10 (P = 0.13). Assessing for divergent
      validity against quality of life measures, the correlation with the DFI was low
      (r = 0.29, P < 0.0001). Comparing the change scores from baseline to week 12 for
      SASSAD, POEM and DFI with the change in accelerometer scores we found low,
      negative correlations (r = -0.02, P = 0.77; r = -0.12, P = 0.06; and r = -0.01, P
      = 0.87, respectively). In general, the units were well tolerated but suggestions
      were made that could improve their usability in children. CONCLUSIONS: Actigraphy
      did not correlate well with disease severity or quality of life when used as an
      objective outcome measure in a multicentre clinical trial, and was not responsive
      to change over time. Further work is needed to establish why this might be, and
      to establish improved methods of distinguishing between eczema-related and eczema
      nonrelated movements.

PMID- 22970692
TI  - Contribution of communication inequalities to disparities in human papillomavirus
      vaccine awareness and knowledge.
AB  - OBJECTIVES: We examined the association of Internet-related communication
      inequalities on human papillomavirus (HPV) vaccine awareness and infection
      knowledge. METHODS: We drew data from National Cancer Institute's 2007 Health
      Information National Trends Survey (n = 7674). We estimated multivariable
      logistic regression models to assess Internet use and Internet health information
      seeking on HPV vaccine awareness and infection knowledge. RESULTS: Non-Internet
      users, compared with general Internet users, had significantly lower odds of
      being aware of the HPV vaccine (odds ratio [OR] = 0.42; 95% confidence interval
      [CI] = 0.34, 0.51) and knowing that HPV causes cervical cancer (OR = 0.70; 95% CI
      = 0.52, 0.95). Among general health information seekers, non-Internet seekers
      compared with Internet information seekers exhibit significantly lower odds of
      HPV vaccine awareness (OR = 0.59; 95% CI = 0.46, 0.75), and of knowing about the
      link between HPV infection and cervical cancer (OR = 0.79; 95% CI = 0.63, 0.99)
      and the sexual transmission of HPV (OR = 0.71; 95% CI = 0.57, 0.89). Among cancer
      information seekers, there were no differences in outcomes between Internet
      seekers and non-Internet seekers. CONCLUSIONS: Use of a communication channel,
      such as the Internet, whose use is already socially and racially patterned, may
      widen observed disparities in vaccine completion rates.

PMID- 22970690
TI  - Xenopus laevis RIC-3 enhances the functional expression of the C. elegans
      homomeric nicotinic receptor, ACR-16, in Xenopus oocytes.
AB  - RIC-3 enhances the functional expression of certain nicotinic acetylcholine
      receptors (nAChRs) in vertebrates and invertebrates and increases the
      availability of functional receptors in cultured cells and Xenopus laevis
      oocytes. Maximal activity of RIC-3 may be cell-type dependent, so neither
      mammalian nor invertebrate proteins is optimal in amphibian oocytes. We cloned
      the X. laevis ric-3 cDNA and tested the frog protein in oocyte expression
      studies. X. laevis RIC-3 shares 52% amino acid identity with human RIC-3 and only
      17% with that of Caenorhabditis elegans. We used the C. elegans nicotinic
      receptor, ACR-16, to compare the ability of RIC-3 from three species to enhance
      receptor expression. In the absence of RIC-3, the proportion of oocytes
      expressing detectable nAChRs was greatly reduced. Varying the ratio of acr-16 to
      X. laevis ric-3 cRNAs injected into oocytes had little impact on the total cell
      current. When X. laevis, human or C. elegans ric-3 cRNAs were co-injected with
      acr-16 cRNA (1 : 1 ratio), 100 MUM acetylcholine induced larger currents in
      oocytes expressing X. laevis RIC-3 compared with its orthologues. This provides
      further evidence for a species-specific component of RIC-3 activity, and suggests
      that X. laevis RIC-3 is useful for enhancing the expression of invertebrate
      nAChRs in X. laevis oocytes.

PMID- 22970693
TI  - Surveillance for Guillain-Barre syndrome after influenza vaccination among the
      Medicare population, 2009-2010.
AB  - OBJECTIVES: We implemented active surveillance for Guillain-Barre syndrome (GBS)
      following seasonal or H1N1 influenza vaccination among the Medicare population
      during the 2009-2010 influenza season. METHODS: We used weekly Medicare claims
      data to monitor vaccinations and subsequent hospitalizations with principal
      diagnosis code for GBS within 42 days. Group sequential testing assessed whether
      the observed GBS rate exceeded a critical limit based on the expected rate from 5
      previous years adjusted for claims delay. We evaluated the lag between date of
      service and date of claims availability and used it for adjustment. RESULTS: By
      July 30, 2010 (after 26 interim surveillance tests), 14.0 million seasonal and
      3.3 million H1N1 vaccinations had accrued. Taking into account claims delay
      appropriately lowered the critical limit during early monitoring. The observed
      GBS rate was below the critical limit throughout the surveillance. CONCLUSIONS:
      Medicare data contributed rapid safety monitoring among millions of 2009-2010
      influenza vaccine recipients. Adjustment for claims delay facilitates early
      detection of potential safety issues. Although limited by lack of medical record
      review to confirm cases, this claims-based surveillance did not indicate a
      statistically significant elevated GBS rate following seasonal or H1N1 influenza
      vaccination.

PMID- 22970697
TI  - Prevalence of the primary LHON mutations in Northern Finland associated with
      bilateral optic atrophy and tobacco-alcohol amblyopia.
AB  - PURPOSE: Leber hereditary optic neuropathy (LHON) is regarded as the most common
      mitochondrial disease. We have previously reported comprehensive population-based
      epidemiological data on common mitochondrial DNA (mtDNA) mutations including
      m.3243A>G, m.8344A>G and large-scale mtDNA deletions in Northern Finland. Our aim
      was to investigate the prevalence of primary LHON mutations and mutations in the
      four mtDNA genes considered hot spots for LHON in the same population. METHODS:
      The study population consisted of 42 adult patients with an aetiologically
      undefined bilateral optic atrophy. The major LHON mutations m.3460G>A, m.11778G>A
      and m.14484T>C were analysed by restriction fragment length polymorphism (RFLP),
      and MTND1, MTND6 and MTATP6 genes were sequenced. MTND5 gene was analysed by
      conformation-sensitive gel electrophoresis (CSGE). RESULTS: No major LHON
      mutations were found in the population of the province of Northern Ostrobothnia
      giving the prevalence of these mutations 0-1.36:100 000 (95% CI). However, two
      main mutations were found elsewhere in Northern Finland, homoplasmic m.11778G>A
      from Kainuu and heteroplasmic m.3460G>A from Central Ostrobothnia. Furthermore,
      tobacco-alcohol amblyopia was diagnosed in five patients in the study population
      and one of them had m.11778G>A. CONCLUSION: The prevalence of the three major
      LHON mutations is lower in Northern Finland than elsewhere in Finland or in
      Western Europe. As LHON and tobacco-alcohol amblyopia have a similar phenotype,
      we recommend analysing the known LHON-associated mutations before setting tobacco
      alcohol amblyopia diagnosis.

PMID- 22970696
TI  - Text data extraction for a prospective, research-focused data mart:
      implementation and validation.
AB  - BACKGROUND: Translational research typically requires data abstracted from
      medical records as well as data collected specifically for research.
      Unfortunately, many data within electronic health records are represented as text
      that is not amenable to aggregation for analyses. We present a scalable open
      source SQL Server Integration Services package, called Regextractor, for
      including regular expression parsers into a classic extract, transform, and load
      workflow. We have used Regextractor to abstract discrete data from textual
      reports from a number of 'machine generated' sources. To validate this package,
      we created a pulmonary function test data mart and analyzed the quality of the
      data mart versus manual chart review. METHODS: Eleven variables from pulmonary
      function tests performed closest to the initial clinical evaluation date were
      studied for 100 randomly selected subjects with scleroderma. One research
      assistant manually reviewed, abstracted, and entered relevant data into a
      database. Correlation with data obtained from the automated pulmonary function
      test data mart within the Northwestern Medical Enterprise Data Warehouse was
      determined. RESULTS: There was a near perfect (99.5%) agreement between results
      generated from the Regextractor package and those obtained via manual chart
      abstraction. The pulmonary function test data mart has been used subsequently to
      monitor disease progression of patients in the Northwestern Scleroderma Registry.
      In addition to the pulmonary function test example presented in this manuscript,
      the Regextractor package has been used to create cardiac catheterization and
      echocardiography data marts. The Regextractor package was released as open source
      software in October 2009 and has been downloaded 552 times as of 6/1/2012.
      CONCLUSIONS: Collaboration between clinical researchers and biomedical
      informatics experts enabled the development and validation of a tool
      (Regextractor) to parse, abstract and assemble structured data from text data
      contained in the electronic health record. Regextractor has been successfully
      used to create additional data marts in other medical domains and is available to
      the public.

PMID- 22970698
TI  - Ubiquitin initiates sorting of Golgi and plasma membrane proteins into the
      vacuolar degradation pathway.
AB  - BACKGROUND: In yeast and mammals, many plasma membrane (PM) proteins destined for
      degradation are tagged with ubiquitin. These ubiquitinated proteins are
      internalized into clathrin-coated vesicles and are transported to early endosomal
      compartments. There, ubiquitinated proteins are sorted by the endosomal sorting
      complex required for transport (ESCRT) machinery into the intraluminal vesicles
      of multivesicular endosomes. Degradation of these proteins occurs after endosomes
      fuse with lysosomes/lytic vacuoles to release their content into the lumen. In
      plants, some PM proteins, which cycle between the PM and endosomal compartments,
      have been found to be ubiquitinated, but it is unclear whether ubiquitin is
      sufficient to mediate internalization and thus acts as a primary sorting signal
      for the endocytic pathway. To test whether plants use ubiquitin as a signal for
      the degradation of membrane proteins, we have translationally fused ubiquitin to
      different fluorescent reporters for the plasma membrane and analyzed their
      transport. RESULTS: Ubiquitin-tagged PM reporters localized to endosomes and to
      the lumen of the lytic vacuole in tobacco mesophyll protoplasts and in tobacco
      epidermal cells. The internalization of these reporters was significantly reduced
      if clathrin-mediated endocytosis was inhibited by the coexpression of a mutant of
      the clathrin heavy chain, the clathrin hub. Surprisingly, a ubiquitin-tagged
      reporter for the Golgi was also transported into the lumen of the vacuole.
      Vacuolar delivery of the reporters was abolished upon inhibition of the ESCRT
      machinery, indicating that the vacuolar delivery of these reporters occurs via
      the endocytic transport route. CONCLUSIONS: Ubiquitin acts as a sorting signal at
      different compartments in the endomembrane system to target membrane proteins
      into the vacuolar degradation pathway: If displayed at the PM, ubiquitin triggers
      internalization of PM reporters into the endocytic transport route, but it also
      mediates vacuolar delivery if displayed at the Golgi. In both cases, ubiquitin
      tagged proteins travel via early endosomes and multivesicular bodies to the lytic
      vacuole. This suggests that vacuolar degradation of ubiquitinated proteins is not
      restricted to PM proteins but might also facilitate the turnover of membrane
      proteins in the early secretory pathway.

PMID- 22970699
TI  - Testosterone concentrations in young pubertal and post-pubertal obese males.
AB  - OBJECTIVE: Obesity in adult males is associated with hypogonadotropic
      hypogonadism. We evaluated the effect of obesity on plasma testosterone
      concentrations in pubertal and post-pubertal young males. DESIGN AND METHODS:
      Morning fasting blood samples were obtained from 25 obese [body mass index (BMI)
      >=95th percentile] and 25 lean (BMI <85th percentile) males between the ages 14
      20 years with Tanner staging >=4. Total (TT) and free testosterone (FT) and
      estradiol concentrations were measured by liquid chromatography tandem mass
      spectrometry and equilibrium dialysis. Free testosterone was also calculated
      using SHBG and albumin. C-reactive protein (CRP), insulin and glucose
      concentrations were measured and homoeostasis model of insulin resistance (HOMA
      IR) was calculated. RESULTS: After controlling for age and Tanner staging, obese
      males had a significantly lower total testosterone (10.5 vs 21.44 nmol/l), free
      testosterone (0.22 vs 0.39 nmol/l) and calculated free testosterone (0.26 vs 0.44
      nmol/l) concentrations as compared to lean males (P < 0.001 for all). Obese males
      had higher CRP concentrations (2.8 vs 0.8 mg/l; P < 0.001), and HOMA-IR (3.8 vs
      1.1; P < 0.001) than lean males. Free testosterone concentrations were positively
      related to age and negatively to BMI, HOMA-IR and CRP concentrations. Total and
      free estradiol concentrations were significantly lower in males with subnormal
      testosterone concentrations. CONCLUSION: Testosterone concentrations of young
      obese pubertal and post-pubertal males are 40-50% lower than those with normal
      BMI. Obesity in young males is associated with low testosterone concentrations,
      which are not secondary to an increase in estradiol concentrations. Our results
      need to be confirmed in a larger number of subjects.

PMID- 22970701
TI  - Genetic variation of wheat streak mosaic virus in the United States Pacific
      Northwest.
AB  - Wheat streak mosaic virus (WSMV), the cause of wheat streak mosaic, is a
      widespread and damaging pathogen of wheat. WSMV is not a chronic problem of
      annual wheat in the United States Pacific Northwest but could negatively affect
      the establishment of perennial wheat, which is being developed as an alternative
      to annual wheat to prevent soil erosion. Fifty local isolates of WSMV were
      collected from 2008 to 2010 near Lewiston, ID, Pullman, WA, and the United States
      Department of Agriculture Central Ferry Research Station, near Pomeroy, WA to
      determine the amount of genetic variation present in the region. The coat protein
      gene from each isolate was sequenced and the data subjected to four different
      methods of phylogenetic analyses. Two well-supported clades of WSMV were
      identified. Isolates in clade I share sequence similarity with isolates from
      Central Europe; this is the first report of isolates from Central Europe being
      reported in the United States. Isolates in clade II are similar to isolates
      originating from Australia, Argentina, and the American Pacific Northwest. Nine
      isolates showed evidence of recombination and the same two well-supported clades
      were observed when recombinant isolates were omitted from the analysis. More
      polymorphic sites, parsimony informative sites, and increased diversity were
      observed in clade II than clade I, suggesting more recent establishment of the
      virus in the latter. The observed diversity within both clades could make
      breeding for durable disease resistance in perennial wheat difficult if there is
      a differential response of WSMV resistance genes to isolates from different
      clades.

PMID- 22970700
TI  - Distinct sites within the vascular cell adhesion molecule-1 (VCAM-1) cytoplasmic
      domain regulate VCAM-1 activation of calcium fluxes versus Rac1 during leukocyte
      transendothelial migration.
AB  - Vascular adhesion molecules regulate the migration of leukocytes from the blood
      into tissue during inflammation. Binding of leukocytes to vascular cell adhesion
      molecule-1 (VCAM-1) activates signals in endothelial cells, including Rac1 and
      calcium fluxes. These VCAM-1 signals are required for leukocyte transendothelial
      migration on VCAM-1. However, it has not been reported whether the cytoplasmic
      domain of VCAM-1 is necessary for these signals. Interestingly, the 19-amino acid
      sequence of the VCAM-1 cytoplasmic domain is 100% conserved among many mammalian
      species, suggesting an important functional role for the domain. To examine the
      function of the VCAM-1 cytoplasmic domain, we deleted the VCAM-1 cytoplasmic
      domain or mutated the cytoplasmic domain at amino acid N724, S728, Y729, S730, or
      S737. The cytoplasmic domain and S728, Y729, S730, or S737 were necessary for
      leukocyte transendothelial migration. S728 and Y729, but not S730 or S737, were
      necessary for VCAM-1 activation of calcium fluxes. In contrast, S730 and S737,
      but not S728 or Y729, were necessary for VCAM-1 activation of Rac1. These
      functional data are consistent with our computational model of the structure of
      the VCAM-1 cytoplasmic domain as an alpha-helix with S728 and Y729, and S730 and
      S737, on opposite sides of the alpha-helix. Together, these data indicate that
      S728 and Y729, and S730 and S737, are distinct functional sites that coordinate
      VCAM-1 activation of calcium fluxes and Rac1 during leukocyte transendothelial
      migration.

PMID- 22970702
TI  - Sensomics analysis of taste compounds in balsamic vinegar and discovery of 5
      acetoxymethyl-2-furaldehyde as a novel sweet taste modulator.
AB  - Sensory-directed fractionation of traditional balsamic vinegar of Modena (TBV)
      led to the identification of the sweet-bitter tasting hexose acetates 6-O-acetyl
      alpha/beta-d-glucopyranose and 1-O-acetyl-beta-d-fructopyranose as well as the
      previously unknown sweetness modulator 5-acetoxymethyl-2-furaldehyde. Taste re
      engineering experiments and sensory time-intensity studies confirmed 5
      acetoxymethyl-2-furaldehyde to contribute to the typical long-lasting sweet taste
      quality of TBV. Moreover, the response of the sweet taste receptor to this
      furaldehyde was verified by means of a functional hTAS1R2/hTAS1R3 receptor assay.
      Quantitative analysis of a total of 59 nonvolatile sensometabolites and taste
      modulators revealed higher concentrations of the sweet-modulating 5-acetoxymethyl
      2-furaldehyde, nonvolatile organic acids and polyphenols such as wood-derived
      ellagitannins, and lower concentrations of acetic acid in the premium quality TBV
      when compared to balsamic vinegar of Modena (BV). Quantitative monitoring of
      sensometabolites throughout TBV manufacturing, followed by agglomerative
      hierarchical clustering and sensomics heatmapping, gave molecular insights into
      the taste alterations occurring during TBV maturation. 

PMID- 22970704
TI  - Experimental and theoretical study on the photophysical properties of 90 degrees 
      and 60 degrees  bimetallic platinum complexes.
AB  - The 90 degrees  and 60 degrees  bimetallic platinum complexes with special
      structures are widely used in coordination-driven self-assembled
      metallosupramolecular architectures, and these complexes are the key components
      of triangular, rectangular, and polygonal metallacycle and metallocage
      supramolecules. Therefore, spectroscopic techniques and quantum chemistry
      calculations were employed in this article to investigate the photophysical
      properties of these bimetallic platinum complexes. Compared with spectra for the
      ligands, the absorption spectra of these Pt complexes are red-shifted, and the
      fluorescence spectra become wider and are also red-shifted. Moreover, the reasons
      for the low fluorescence quantum yields and short fluorescence lifetimes of these
      compounds were investigated using quantum chemistry calculations. We demonstrate
      that the fluorescent states of the bimetallic platinum complexes can be
      considered as local excited states, and that they possess a ligand-centered pi
      pi* transition feature. Meanwhile, the platinum metals act as perturbation for
      these transitions, whereas the nonfluorescent states are classified as
      intramolecular charge-transfer states. Furthermore, a new fluorescence modulation
      mechanism is developed to explain the different emission processes of these
      complexes with different ligands.

PMID- 22970703
TI  - Measuring cognitive and affective constructs in the context of an acute health
      event.
AB  - The latest recommendations for building dynamic health behavior theories
      emphasize that cognitions, emotions, and behaviors--and the nature of their inter
      relationships--can change over time. This paper describes the development and
      psychometric validation of four scales created to measure smoking-related causal
      attributions, perceived illness severity, event-related emotions, and intention
      to quit smoking among patients experiencing acute cardiac symptoms. After
      completing qualitative work with a sample of 50 cardiac patients, we administered
      the scales to 300 patients presenting to the emergency department for cardiac
      related symptoms. Factor analyses, alpha coefficients, ANOVAs, and Pearson
      correlation coefficients were used to establish the scales' reliability and
      validity. Factor analyses revealed a stable factor structures for each of the
      four constructs. The scales were internally consistent, with the majority having
      an alpha of >0.80 (range: 0.57-0.89). Mean differences in ratings of the
      perceived illness severity and event-related emotions were noted across the three
      time anchors. Significant increases in intention to quit at the time of
      enrollment, compared to retrospective ratings of intention to quit before the
      event, provide preliminary support for the sensitivity of this measure to the
      motivating impact of the event. Finally, smoking-related causal attributions,
      perceived illness severity, and event-related emotions correlated in the expected
      directions with intention to quit smoking, providing preliminary support for
      construct validity.

PMID- 22970705
TI  - Vibrational spectroscopic imaging and multiphoton microscopy of spinal cord
      injury.
AB  - Spinal cord injury triggers a series of complex biochemical alterations of
      nervous tissue. Up to now, such cellular events could not be studied without
      conventional tissue staining. The development of optical, label-free imaging
      techniques could provide powerful monitoring tools with the potential to be
      applied in vivo. In this work, we assess the ability of vibrational spectroscopy
      to generate contrast at molecular level between normal and altered regions in a
      rat model of spinal cord injury. Using tissue sections, we demonstrate that
      Fourier transform infrared (FT-IR) spectroscopy and spontaneous Raman
      spectroscopy are able to identify the lesion, the surrounding scar, and unharmed
      normal tissue, delivering insight into the biochemical events induced by the
      injury and allowing mapping of tissue degeneration. The FT-IR and Raman
      spectroscopic imaging provides the basis for fast multimodal nonlinear optical
      microscopy (coherent anti-Stokes Raman scattering, endogenous two-photon
      fluorescence, and second harmonic generation). The latter proves to be a fast
      tool for imaging of the lesion on unstained tissue samples, based on the
      alteration in lipid content, extracellular matrix composition, and
      microglia/macrophages distribution pattern. The results establish these
      technologies in the field of regeneration in central nervous system, with the
      long-term goal to extend them to intravital use, where fast and nonharmful
      imaging is required.

PMID- 22970706
TI  - Pharmacokinetic evaluation of  argatroban  for the treatment of acute coronary
      syndrome.
AB  - INTRODUCTION: Limitations and contraindications of heparins and oral vitamin K
      antagonists have led to the development of new anticoagulant drugs over the last
      few years. Argatroban is an intravenous direct thrombin inhibitor currently
      indicated for the prophylaxis and treatment of thrombosis associated with heparin
      induced thrombocytopenia (HIT) and for patients at risk of HIT undergoing
      percutaneous coronary intervention (PCI). The role of argatroban for the
      treatment of acute coronary syndrome (ACS) is under evaluation. AREAS COVERED:
      This article reviews the potential use of argatroban for the treatment of ACS and
      presents the pharmacokinetic data currently available. The authors also present
      the pharmacodynamic literature of agratroban in addition to highlighting the
      safety and tolerability of the drug. EXPERT OPINION: Theoretically, argatroban's
      pharmacokinetics makes it an attractive alternative to heparin. Pharmacological
      advantages of argatroban over heparin include a more-predictable anticoagulant
      response and the absence of a risk of HIT. Furthermore, argatroban has a fast and
      predictable dose-dependent anticoagulant effect with low inter-individual
      variability. It is non-immugenic, not susceptible to degradation by proteases and
      it is cleared via the liver. These characteristics confer argotroban a different
      profile from other anticoagulants. Agatroban is an effective alternative for
      patients when heparin, lepirudin and bivalirudin cannot be used. Its utility in
      ACS and PCI in non-HIT patients has been evaluated but further studies are
      warranted to define its role in this context.

PMID- 22970707
TI  - The authors' reply: Predicting hypothyroidism from the Wickham Survey.

PMID- 22970708
TI  - First record of Calliephialtes sittenfeldae associated with the tephritid fruit
      fly Anastrepha spatulata in Mexico.
AB  - This paper reports for the first time an ichneumonid parasitoid Calliephialtes
      sittenfeldae Gauld Ugalde-Gomez et Hanson (Hymenoptera: Ichneumonidae) associated
      with a dipteran host Anastrepha spatulata Stone (Diptera: Tephritidae), recovered
      from fruit of Schoepfia schreberi (Santalales: Olacaceae) in central Veracruz,
      Mexico. Large numbers of this parasitoid were collected and reared from its fruit
      fly host in three localities of Veracruz, Mexico. Some observations of its
      biology are also reported. This is a first record of C. sittenfeldae from Mexico,
      and the first record of this parasitoid species, its insect host, and the host
      plant. The male of this species is described and illustrated for the first time.

PMID- 22970710
TI  - The U.S. drought of 2012.

PMID- 22970709
TI  - The ophthalmological complications of targeted agents in cancer therapy: what do
      we need to know as ophthalmologists?
AB  - Recently, there has been an increase in the use of targeted therapies for cancer
      treatments. Nevertheless, the ocular side-effects of the commonly used targeted
      agents are generally under-reported and not well studied in the literature. We
      conducted multiple searches in databases, including Medline, EMBASE, Cochrane
      Library and conference proceedings, using the following strings: 'name of
      targeted therapeutic agent (both generic and commercial names)' AND 'eye OR
      ocular OR vision OR ophthalmological'. Various targeted agents have been found to
      be associated with ocular side-effects due to their specific targeting of
      activities in the eye. Imatinib commonly causes periorbital oedema, epiphora and
      occasionally conjunctival haemorrhage. Cetuximab causes corneal lesions,
      meibomian gland dysfunction, periorbital and lid dermatitis, blepharitis and
      conjunctivitis. Erlotinib is related to various ocular toxicities, mainly on the
      ocular surface, and perifosine has been reported to be associated with severe
      keratitis. Bevacizumab could potentially disrupt intrinsic ocular circulation and
      lead to the development of thromboembolic events; there are rare reported cases
      of optic neuritis or optic neuropathy. Other targeted agents, such as
      trastuzumab, sunitinib and crizotinib, also have specific ocular toxicities. In
      conclusion, ocular effects of targeted agents are not uncommon in cancer patients
      receiving targeted therapy. Ophthalmologists should have high indexes of
      suspicion to diagnose and treat these complications promptly. 

PMID- 22970711
TI  - Whole genome expression profiling based on paraffin embedded tissue can be used
      to classify diffuse large B-cell lymphoma and predict clinical outcome.
AB  - This study tested the validity of whole-genome expression profiling (GEP) using
      RNA from formalin-fixed, paraffin-embedded (FFPE) tissue to sub-classify Diffuse
      Large B-cell Lymphoma (DLBCL), in a population based cohort of 172 patients. GEP
      was performed using Illumina Whole Genome cDNA-mediated Annealing, Selection,
      extension & Ligation, and tumours were classified into germinal centre (GCB),
      activated B-cell (ABC) and Type-III subtypes. The method was highly reproducible
      and reliably classified cell lines of known phenotype. GCB and ABC subtypes were
      each characterized by unique gene expression signatures consistent with
      previously published data. A significant relationship between subtype and
      survival was observed, with ABC having the worst clinical outcome and in a
      multivariate survival model only age and GEP class remained significant. This
      effect was not seen when tumours were classified by immunohistochemistry. There
      was a significant association between age and subtype (mean ages ABC - 72.8
      years, GC - 68.4 years, Type-III - 64.5 years). Older patients with ABC subtype
      were also over-represented in patients who died soon after diagnosis. The
      relationship between prognosis and subtype improved when only patients assigned
      to the three categories with the highest level of confidence were analysed. This
      study demonstrates that GEP-based classification of DLBCL can be applied to RNA
      extracted from routine FFPE samples and has potential for use in stratified
      medicine trials and clinical practice.

PMID- 22970712
TI  - XBP1 depletion precedes ubiquitin aggregation and Golgi fragmentation in TDP-43
      transgenic rats.
AB  - Protein inclusion is a prominent feature of neurodegenerative diseases including
      frontotemporal lobar degeneration (FTLD) that is characterized by the presence of
      ubiquitinated TDP-43 inclusion. Presence of protein inclusions indicates an
      interruption to protein degradation machinery or the overload of misfolded
      proteins. In response to the increase in misfolded proteins, cells usually
      initiate a mechanism called unfolded protein response (UPR) to reduce misfolded
      proteins in the lumen of endoplasmic reticules. Here, we examined the effects of
      mutant TDP-43 on the UPR in transgenic rats that express mutant human TDP-43
      restrictedly in the neurons of the forebrain. Over-expression of mutant TDP-43 in
      rats caused prominent aggregation of ubiquitin and remarkable fragmentation of
      Golgi complexes prior to neuronal loss. While ubiquitin aggregates and Golgi
      fragments were accumulating, neurons expressing mutant TDP-43 failed to up
      regulate chaperones residing in the endoplasmic reticules and failed to initiate
      the UPR. Prior to ubiquitin aggregation and Golgi fragmentation, neurons were
      depleted of X-box-binding protein 1 (XBP1), a key player of UPR machinery.
      Although it remains to determine how mutation of TDP-43 leads to the failure of
      the UPR, our data demonstrate that failure of the UPR is implicated in TDP-43
      pathogenesis.

PMID- 22970713
TI  - Role of gut microbiota in liver diseases.
AB  - The liver constantly encounters food-derived antigens and bacterial components
      such as lipopolysaccharide translocated from the gut into the portal vein.
      Bacterial components stimulate Toll-like receptors (TLR), which are expressed on
      Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells,
      endothelial cells and dendritic cells and recognize specific pathogen-associated
      molecular patterns. The signaling of TLR to its main ligand triggers
      inflammation. Usually, in order to protect against hyperactivation of the immune
      system and to prevent organ failure by persistent inflammation, TLR tolerance to
      repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR
      tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural
      killer T cells are key components of innate immunity. Decreased numbers and
      impaired ability of these cells lead to failures in immune tolerance, resulting
      in persistent inflammation. Recently, the activation of inflammasome was revealed
      to control the secretion of pro-inflammatory cytokines such as interleukin-1beta
      in response to bacterial pathogens. Innate immunity seems to be an important
      contributor to the pathogenesis of fatty liver disease and autoimmune liver
      disease. Recently, probiotics were reported to affect various liver diseases via
      shifts in gut microbiota and the stability of intestinal permeability. However,
      many unresolved questions remain. Further analysis will be needed to gain a more
      comprehensive understanding of the association of innate immunity with the
      pathogenesis of various liver diseases.

PMID- 22970714
TI  - It's time: a new era for paediatrics and child health in Australia.
AB  - The Australian College of Paediatrics (ACP) was established in 1978; part of the
      stated rationale was to 'acquire equal status to other colleges in medicine' ...
      and to become ... 'to which governments, or other organisations dealing with
      children, could officially turn to for advice'. After less than 2 decades, the
      ACP ceased to exist, and paediatricians became members of the Paediatrics and
      Child Health Division of the Royal Australasian College of Physicians (RACP).
      Many would now argue that the decision to dissolve the ACP and instead become a
      division within the RACP, though not taken lightly and made for what seemed at
      the time to be good reasons, might have been a mistake. While there have been
      some benefits, overall the public profile and national influence of
      paediatricians has been diminished. Paediatricians as a group have had little
      influence on policy formulation as it pertains to children and families, and the
      present administrative arrangements within the RACP raise considerable
      bureaucratic barriers for paediatricians to be able to contribute in a
      constructive and timely manner. It is suggested that paediatricians cannot be
      effective advocates for the health and wellbeing of children when they are but a
      relatively small and powerless group that resides within a large body of
      professionals whose primary interest is in various aspects of adult medicine. It
      is time that paediatricians (re)established their own college and controlled
      their own destiny. While such a step is not without its challenges, many would
      argue that it is an essential and timely step if we are to address our political
      and public health responsibilities.

PMID- 22970715
TI  - In vitro evaluation of the efficacy of commercial green tea extracts in UV
      protection.
AB  - Plants with antioxidant properties are beneficial for preventing the ageing
      events evoked by UV light, and numerous products based on Camellila sinensis
      (green tea) are commercially available, many of which claiming to contain
      bioactive compounds that would prevent UV-induced skin damage. In this study, we
      tested the efficacy of five commercial green tea extracts used to enrich cosmetic
      formulations for protecting human and mouse fibroblasts against UV radiation
      effects and compared with a fluid one prepared according to the Brazilian
      Pharmacopoeia recommendations. Taking into consideration that the ageing process
      can be accelerated by solar radiation by excessive free radical generation,
      leading to depletion of skin antioxidant defences, and its collapse caused by
      disruption of the metalloproteinase metabolism, we have used their individual (-)
      epigallocathechin-3-gallate (EGCG) content, the catalase and SOD status and the
      matrix-degrading metalloproteases (MMP)-1, MMP-9 and MMP-13 levels as comparative
      parameters. The EGCG content of the commercial products showed wide variability,
      ranging from undetectable levels to 58.65 +/- 1.12 MUg mL(-1) , in contrast with
      the fluid extract (87.82 +/- 1.35 MUg mL(-1) ). Moreover, only the pharmacopoeic
      extract was able to significantly reduce MMP degradation while enhancing the
      levels of SOD and catalase. These results indicate, for the first time, that the
      methodologies for preparing herbal mixtures can interfere significantly with
      compounds endowed with photoprotective effects, and the efficacy of products
      containing C. sinensis extracts thought to act against effects of solar radiation
      can be compromised.

PMID- 22970716
TI  - Immersion depth of positively versus negatively charged nanoparticles at the air
      water interface: a Poisson-Boltzmann model.
AB  - Electrostatic interactions affect the immersion depth of charged nanoparticles
      that are trapped at an air-water interface. Recent experiments indicate that upon
      adding salt negatively charged nanoparticles penetrate deeper into the aqueous
      phase, whereas positively charged nanoparticles exhibit opposite behavior. It has
      been proposed that this unexpected lack of invariance with respect to the
      nanoparticle's charge reversal is caused by a negative surface potential of the
      air-water interface. To support this hypothesis, we have performed detailed
      calculations based on nonlinear Poisson-Boltzmann theory of individual spherical
      particles that are either negatively or positively charged and reside at the
      interface between air and water. The nanoparticles possess dissociable surface
      groups that become charged when exposed to the aqueous environment. We calculate
      the optimal immersion depth from a numerical minimization of the total free
      energy, which we express as the sum of a surface tension term and an
      electrostatic contribution. In all calculations we fix the surface potential at
      the air-water surface at -50 mV. In qualitative agreement with recent
      experiments, our model predicts opposite behaviors of negatively versus
      positively charged nanoparticles: adding salt increases/decreases the water
      immersion depth of negatively/positively charged nanoparticles.

PMID- 22970717
TI  - Standard operating procedures for taking a sexual history.
AB  - INTRODUCTION: While there is evidence of increased professional and public
      awareness of sexual problems, both male and female sexual dysfunctions remain
      underdiagnosed and undertreated by health care professionals around the world.
      Health care professionals (HCPs) are typically reluctant, disinterested, or
      unskilled in sexual problem management and regrettably are often disinclined to
      inquire about sexual issues. HCPs in all countries receive variable,
      nonstandardized, or inadequate training in sexual history taking and its
      treatment. AIM: This article presents a standard operating procedure (SOP) for
      taking a sexual history from men or women with sexual problems or performance
      concerns. METHODS: Review of relevant evidence-based literature identified
      through a PubMed search, integrated with expert opinion. RESULTS: Guidelines for
      taking a sexual history are presented along with the relevant domains, opening
      and follow-up questions. CONCLUSIONS: The SOP presented in this article offers
      HCPs a brief, structured, and uniform method for obtaining a sexual history from
      men or women seeking health care services. Sexual history taking should be based
      on three basic principles, which serve as the foundation for managing sexual
      problems in men and women. These include the following: (i) a patient-centered
      approach; (ii) evidenced-based diagnostic and treatment recommendations; and
      (iii) use of a unified management approach for men and women. Sexual history
      taking should always be conducted in a culturally sensitive manner, taking
      account of the individual's background and lifestyle, status of the partner
      relationship, and the clinician's comfort and experience with the topic. Sexual
      inquiry should be incorporated into all new patient encounters, when possible, if
      only to ask one or two broad questions such as the following: "Are you sexually
      active? Do you have any sexual concerns or problems you would like to discuss?"
      Sexual history taking is a cornerstone of sexual medicine clinical practice. All
      patients should be provided an opportunity for frank and open discussion of
      sexual issues or concerns, conducted in an atmosphere of sensitivity and respect.

PMID- 22970718
TI  - Mechanism of polarization fatigue in BiFeO3.
AB  - Fatigue in ferroelectric oxides has been a long lasting research topic since the
      development of ferroelectric memory in the late 1980s. Over the years, different
      models have been proposed to explain the fatigue phenomena. However, there is
      still debate on the roles of oxygen vacancies and injected charges. The main
      difficulty in the study of fatigue in ferroelectric films is that the
      conventional vertical sandwich structure prevents direct observation of the
      microscopic evolution through the film thickness during the electric field
      cycling. To circumvent this problem, we take advantage of the large in-plane
      polarization of BiFeO(3) and conduct direct domain and local electrical
      characterizations using a planar device structure. The combination of
      piezoresponse force microscopy and scanning kelvin probe microscopy allows us to
      study the local polarization and space charges simultaneously. It is observed
      that charged domain walls are formed during the electrical cycling, but they do
      not cause polarization fatigue. After prolonged cycling, injected charges appear
      at the electrode/film interfaces, where domains are pinned. When the pinned
      domains grow across the channel, macroscopic fatigue appears. The role of
      injected charges in polarization fatigue of BiFeO(3) is clearly demonstrated.

PMID- 22970720
TI  - The properties, functions, and use of selenium compounds in living organisms.
AB  - Selenium occurs in the environment in inorganic and organic compounds. For many
      years it was regarded as a toxic element, causing numerous illnesses and
      diseases. But research in the past 50 years has revealed a "bright side" to this
      element, especially as a component of selenoproteins, selenium makes a
      significant contribution to the health of humans and animals. The selenium
      content in an organism depends on its concentration and bioavailability in the
      soil, and the differences between its deficiency, appropriate intake, and excess
      are very slight. This article gathers information from the literature on: * the
      consequences of a deficiency and an excess of selenium in the body, as well as
      the health-promoting mechanisms of selenium, including the functions of
      selenoproteins * the uptake and transformation of selenium compounds by plants,
      because of the fact that selenium is better assimilated from plant food and also
      the classification of plants with respect to their ability to take up selenium
      from the soil and to accumulate it.

PMID- 22970721
TI  - Guidelines for asbestos remediation at Italian superfund sites.
AB  - Asbestos is now banned in 52 countries. Although Italy banned asbestos in 1992,
      up until that date it had been one of the main producer nations of asbestos and
      asbestos-containing materials, and asbestos-related contamination is still
      widespread in the country. To reduce asbestos-related health effects, Italy has
      adopted many laws and regulations regarding exposure thresholds and remediation
      tools. Even so, there are legislative gaps that are making it difficult to manage
      related risks especially in the operative phase.   The lack of standard
      procedures at a national level regarding emergency shutdown and remediation as
      well as reference thresholds for specific risk situations creates difficulties
      and different actions when dealing with the cleanup of Italian asbestos superfund
      sites. The authors propose operative guidelines for asbestos remediation at
      Italian superfund sites.   INAIL, the reference national organization for
      asbestos-related matters, acting as an advisor to a number of state, regional,
      and local authorities, examined the main asbestos-related risk situations in
      Italy and proposed the most appropriate actions to take. The detailed analysis of
      many actual cases of risk, in part through inspections and the management of
      cleanup actions at asbestos Italian superfund sites, resulted in proposals to
      modify existing procedures and thresholds, which were subsequently discussed with
      all national, regional, and local scientific bodies.   After more than two years
      of work and discussion at a national level, INAIL-DIPIA-Asbestos Group drafted
      new Guidelines for Asbestos Remediation at Italian Superfund sites, and
      officially submitted them to the Environment Ministry. The Ministry then adopted
      the document in regard to all asbestos Italian superfunds. This recently released
      document is also a useful reference for contaminated sites at a regional and
      local level.   The operative Guidelines for Asbestos Remediation at Italian
      Superfund sites may also be of use at an international level for countries that
      have already banned asbestos and are engaged in remediation activity and for
      countries that have not yet banned asbestos but wish to adopt risk prevention
      measures.

PMID- 22970722
TI  - Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of
      experience and remaining challenges.
AB  - In 1964, Christian de Duve first suggested that enzyme replacement might prove
      therapeutic for lysosomal storage diseases (LSDs). Early efforts identified the
      major obstacles, including the inability to produce large quantities of the
      normal enzymes, the lack of animal models for proof-of-concept studies, and the
      potentially harmful immune responses to the "foreign" normal enzymes.
      Subsequently, the identification of receptor-mediated targeting of lysosomal
      enzymes, the cloning and overexpression of human lysosomal genes, and the
      generation of murine models markedly facilitated the development of enzyme
      replacement therapy (ERT). However, ERT did not become a reality until the early
      1990s, when its safety and effectiveness were demonstrated for the treatment of
      type 1 Gaucher disease. Today, ERT is approved for six LSDs, and clinical trials
      with recombinant human enzymes are ongoing in several others. Here, we review the
      lessons learned from 20 years of experience, with an emphasis on the general
      principles for effective ERT and the remaining challenges.

PMID- 22970719
TI  - The role of cadmium and nickel in estrogen receptor signaling and breast cancer:
      metalloestrogens or not?
AB  - During the past half-century, incidences of breast cancer have increased
      globally. Various factors--genetic and environmental--have been implicated in the
      initiation and progression of this disease. One potential environmental risk
      factor that has not received a lot of attention is the exposure to heavy metals.
      While several mechanisms have been put forth describing how high concentrations
      of heavy metals play a role in carcinogenesis, it is unclear whether chronic, low
      level exposure to certain heavy metals (i.e., cadmium and nickel) can directly
      result in the development and progression of cancer. Cadmium and nickel have been
      hypothesized to play a role in breast cancer development by acting as
      metalloestrogens--metals that bind to estrogen receptors and mimic the actions of
      estrogen. Since the lifetime exposure to estrogen is a well-established risk
      factor for breast cancer, anything that mimics its activity will likely
      contribute to the etiology of the disease. However, heavy metals, depending on
      their concentration, are capable of binding to a variety of proteins and may
      exert their toxicities by disrupting multiple cellular functions, complicating
      the analysis of whether heavy metal-induced carcinogenesis is mediated by the
      estrogen receptor. The purpose of this review is to discuss the various
      epidemiological, in vivo, and in vitro studies that show a link between the heavy
      metals, cadmium and nickel, and breast cancer development. We will particularly
      focus on the studies that test whether these two metals act as metalloestrogens
      in order to assess the strength of the data supporting this hypothesis.

PMID- 22970723
TI  - Acute administration of ketamine in rats increases hippocampal BDNF and mTOR
      levels during forced swimming test.
AB  - INTRODUCTION: Previous studies have shown that a single sub-anesthetic dose of
      ketamine exerts fast-acting antidepressant effects in patients and in animal
      models of depression. However, the underlying mechanisms are not totally
      understood. This study aims to investigate the effects of acute administration of
      different doses of ketamine on the immobility time of rats in the forced swimming
      test (FST) and to determine levels of hippocampal brain-derived neurotrophic
      factor (BDNF) and mammalian target of rapamycin (mTOR). METHODS: Forty male
      Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10
      each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day,
      all animals were forced to swim for 15 min. On the second day ketamine (5, 10,
      and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the
      second episode of the forced swimming test. Immobility times of the rats during
      the forced swimming test were recorded. The animals were then decapitated. The
      hippocampus was harvested for determination of BDNF and mTOR levels. RESULTS:
      Compared with group saline, administration of ketamine at a dose of 5, 10, and 15
      mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at
      doses of both 10 and 15 mg/kg showed a significant increase in the expression of
      hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and
      15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P
      < 0.05 for all doses) CONCLUSION: The antidepressant effect of ketamine might be
      related to the increased expression of BDNF and mTOR in the hippocampus of rats.

PMID- 22970725
TI  - The effects of lung volume recruitment on coughing and pulmonary function in
      patients with ALS.
AB  - Our objective was to study the intensity and duration of the effects of lung
      volume recruitment, a manual breath stacking technique, on pulmonary function and
      coughing in individuals with amyotrophic lateral sclerosis (ALS). Twenty-nine
      individuals with ALS participated in this study. A cross-over research design was
      used to compare effects of lung volume recruitment to a control condition.
      Treatment outcome measures included forced vital capacity (FVC), sniff nasal
      pressure (SnP) and peak cough flow (PCF). Results demonstrated that LVR had a
      significantly positive effect on FVC for up to 15 min following treatment but did
      not have a facilitative effect on SnP at any time-point. LVR had a significantly
      positive effect on PCF during unassisted coughing at both 15 min and 30 min
      following treatment, and there was no significant decrease in flow rates from
      baseline to 30 min later. In conclusion, lung volume recruitment may be an
      effective treatment for improving coughing and pulmonary function in individuals
      with ALS. Future research should be focused on determining patient
      characteristics that contribute to response to treatment, as well as randomized
      controlled trials of the technique.

PMID- 22970726
TI  - Orthopaedic co-morbidities in the elderly haemophilia population: a review.
AB  - Due to improvements in the treatment and medical care of haemophilia, the life
      expectancy of individuals with haemophilia has approached that of the general
      population. To review the main co-morbidities of the musculoskeletal system in
      elderly persons with haemophilia, we have performed a review of the literature on
      the musculoskeletal problems of elderly haemophiliacs. Chronic arthropathy is the
      main co-morbidity in the ageing person with haemophilia. Age-related orthopaedic
      co-morbidities include degenerative joint changes, osteoporosis, muscle atrophy
      or sarcopenia, muscle weakness and disturbance of gait and balance. Increased
      pain, muscle weakness and atrophy along with an increased risk of falling are key
      features of advanced haemophilic arthropathy and ageing. An ageing haemophilia
      population in which arthropathy continues to be the primary co-morbidity is a
      current challenge for those responsible for their care. Exercise programmes
      undertaken two to three times per week for at least 12 weeks seem most effective
      in reducing the impact of age-related changes on the musculoskeletal system.
      Establishing effective exercise programmes and strategies to identify individuals
      who would benefit from early surgical intervention together with presurgical
      physiotherapy prehabilitation is a priority for future research.

PMID- 22970727
TI  - Demand for pneumococcal vaccination under subsidy program for the elderly in
      Japan.
AB  - BACKGROUND: Vaccination programs often organize subsidies and public relations in
      order to obtain high uptake rates and coverage. However, effects of subsidies and
      public relations have not been studied well in the literature. In this study, the
      demand function of pneumococcal vaccination among the elderly in Japan is
      estimated, incorporating effects of public relations and subsidy. METHODS: Using
      a data from a questionnaire survey sent to municipalities, the varying and
      constant elasticity models were applied to estimate the demand function. The
      response variable is the uptake rate. Explanatory variables are: subsidy
      supported shot price, operating years of the program, target population size for
      vaccination, shot location intensity, income and various public relations tools.
      The best model is selected by c-AIC, and varying and constant price elasticities
      are calculated from estimation results. RESULTS: The vaccine uptake rate and the
      shot price have a negative relation. From the results of varying price
      elasticity, the demand for vaccination is elastic at municipalities with a shot
      price higher than 3,708 JPY (35.7 USD). Effects of public relations on the uptake
      rate are not found. CONCLUSIONS: It can be suggested that municipalities with a
      shot price higher than 3,708 JPY (35.7 USD) could subsidize more and reduce price
      to increase the demand for vaccination. Effects of public relations are not
      confirmed in this study, probably due to measurement errors of variables used for
      public relations, and studies at micro level exploring individual's response to
      public relations would be required.

PMID- 22970724
TI  - Cyclic AMP dynamics in the pancreatic beta-cell.
AB  - Insulin secretion from pancreatic beta-cells is tightly regulated by glucose and
      other nutrients, hormones, and neural factors. The exocytosis of insulin granules
      is triggered by an elevation of the cytoplasmic Ca(2+) concentration
      ([Ca(2+)](i)) and is further amplified by cyclic AMP (cAMP). Cyclic AMP is formed
      primarily in response to glucoincretin hormones and other G(s)-coupled receptor
      agonists, but generation of the nucleotide is critical also for an optimal
      insulin secretory response to glucose. Nutrient and receptor stimuli trigger
      oscillations of the cAMP concentration in beta-cells. The oscillations arise from
      variations in adenylyl cyclase-mediated cAMP production and phosphodiesterase
      mediated degradation, processes controlled by factors like cell metabolism and
      [Ca(2+)](i). Protein kinase A and the guanine nucleotide exchange factor Epac2
      mediate the actions of cAMP in beta-cells and operate at multiple levels to
      promote exocytosis and pulsatile insulin secretion. The cAMP signaling system
      contains important targets for pharmacological improvement of insulin secretion
      in type 2 diabetes.

PMID- 22970728
TI  - Protein disorder in plants: a view from the chloroplast.
AB  - BACKGROUND: The intrinsically unstructured state of some proteins, observed in
      all living organisms, is essential for basic cellular functions. In this field
      the available information from plants is limited but it has been reached a point
      where these proteins can be comprehensively classified on the basis of disorder,
      function and evolution. RESULTS: Our analysis of plant genomes confirms that
      nuclear-encoded proteins follow the same trend than other multi-cellular
      eukaryotes; however, chloroplast- and mitochondria- encoded proteins conserve the
      patterns of Archaea and Bacteria, in agreement with their phylogenetic origin.
      Based on current knowledge about gene transference from the chloroplast to the
      nucleus, we report a strong correlation between the rate of disorder of
      transferred and nuclear-encoded proteins, even for polypeptides that play
      functional roles back in the chloroplast. We further investigate this trend by
      reviewing the set of chloroplast ribosomal proteins, one of the most
      representative transferred gene clusters, finding that the ribosomal large
      subunit, assembled from a majority of nuclear-encoded proteins, is clearly more
      unstructured than the small one, which integrates mostly plastid-encoded
      proteins. CONCLUSIONS: Our observations suggest that the evolutionary dynamics of
      the plant nucleus adds disordered segments to genes alike, regardless of their
      origin, with the notable exception of proteins currently encoded in both genomes,
      probably due to functional constraints.

PMID- 22970730
TI  - Hemorrhagic complications associated with dabigatran use.
AB  - OBJECTIVE: Dabigatran is a direct thrombin inhibitor approved for anticoagulation
      in non-valvular atrial fibrillation and, in some countries, for thromboembolism
      prophylaxis following select orthopedic surgeries. Despite decreased rates of
      thromboembolism, bleeding remains a risk due to the inability to conveniently
      monitor anticoagulant effect and the lack of a reversal agent. CASE SERIES: We
      present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin,
      clopidogrel, and dabigatran presented with rectal bleeding and epistaxis. He died
      despite transfusion and administration of prothrombin complex concentrate. A 73
      year-old woman on dabigatran and aspirin survived after transfusion and an
      emergent sternotomy for cardiac tamponade. An 86 year-old man with kidney disease
      and thrombocytopenia received packed red blood cells, platelets, and fresh frozen
      plasma for rectal bleeding while on dabigatran. An 80 year-old man on dabigatran
      had a subdural hematoma after falling and hitting his head. Serial imaging showed
      no progression. CONCLUSION: The absence of a reversal agent for dabigatran raises
      concern for uncontrollable bleeding and death. Dabigatran's listed
      contraindications include active bleeding and a history of dabigatran
      hypersensitivity reaction. Wider use may result in bleeding rates higher than
      anticipated from clinical trials. Risks factors that may have contributed to
      bleeding in these patients include concomitant bleeding diathesis, antiplatelet
      agent use, renal insufficiency, advanced age, and fall risks.

PMID- 22970731
TI  - Metabolic risk profile of schoolchildren and joint physical activity with an
      adult in the household: multilevel analysis.
AB  - We aim to examine the relationship between metabolic risk (MR) profile and
      physical activity (PA) with an adult within the household. A total of 4761
      schoolchildren (54% boys) aged 10-16 years old were categorized as either at high
      MR or low MR profile based on their weight and systolic blood pressure status. We
      assessed the frequency of PA with an adult within the household and fitness.
      Multilevel regressions were used to determine the likelihood of being at MR in
      schoolchildren. The proportion of males and females who engage in PA with adults
      daily was 17.4% and 10.4%, respectively. 16.5% male and 17.2% female did not
      engage in any PA with adults at all. Compared with those engaging in PA daily
      with adults in their household, schoolchildren who have reported no such PA were
      54% (OR 1.54, 95% CI, 1.07-2.20) likely to have an elevated MR profile. Those who
      sometimes do PA with adult were 25% (OR 1.25, 95% CI, 0.82-1.93) more likely to
      have a higher MR profile. After adjusting for PA and fitness, PA with adults
      remains a determinant of MR profile in males. Compared with those that reported
      they daily did, schoolchildren were more likely to be unfit if they either
      sometimes engaged in PA with adults (OR 2.11, 95% CI, 1.44-3.09) or never (OR
      2.89, 95% CI, 1.89-4.43). Joint PA with an adult within household could increase
      schoolchildren's fitness level and may reduce the risk of metabolic diseases.

PMID- 22970732
TI  - Guest-host interactions investigated by time-resolved X-ray spectroscopies and
      scattering at MHz rates: solvation dynamics and photoinduced spin transition in
      aqueous Fe(bipy)3(2+).
AB  - We have studied the photoinduced low spin (LS) to high spin (HS) conversion of
      [Fe(bipy)(3)](2+) in aqueous solution. In a laser pump/X-ray probe synchrotron
      setup permitting simultaneous, time-resolved X-ray diffuse scattering (XDS) and X
      ray spectroscopic measurements at a 3.26 MHz repetition rate, we observed the
      interplay between intramolecular dynamics and the intermolecular caging solvent
      response with better than 100 ps time resolution. On this time scale, the initial
      ultrafast spin transition and the associated intramolecular geometric structure
      changes are long completed, as is the solvent heating due to the initial energy
      dissipation from the excited HS molecule. Combining information from X-ray
      emission spectroscopy and scattering, the excitation fraction as well as the
      temperature and density changes of the solvent can be closely followed on the
      subnanosecond time scale of the HS lifetime, allowing the detection of an
      ultrafast change in bulk solvent density. An analysis approach directly utilizing
      the spectroscopic data in the XDS analysis effectively reduces the number of free
      parameters, and both combined permit extraction of information about the
      ultrafast structural dynamics of the caging solvent, in particular, a decrease in
      the number of water molecules in the first solvation shell is inferred, as
      predicted by recent theoretical work.

PMID- 22970733
TI  - The prevalence and relevance of adrenal masses in patients with sporadic
      gastroenteropancreatic neuroendocrine tumours (GEP-NET).
AB  - OBJECTIVE: The widespread application of abdominal computerized tomography (CT)
      imaging has revealed that 0.98-4.0% of individuals harbour adrenal lesions
      (incidentalomas). There is, however, paucity of information regarding the
      prevalence of adrenal lesions in patients with gastroenteropancreatic
      neuroendocrine tumours (GEP-NETS). Purpose of this study was to estimate the
      prevalence of adrenal lesions in patients with GEP-NETS and identify their
      radiological features and clinical significance. DESIGN: The prevalence of
      adrenal lesions was estimated retrospectively in 438 patients with GEP-NETS who
      underwent abdominal imaging. Secretory status and changes in size were documented
      during subsequent follow-up. MEN-1 patients and ectopic ACTH-secreting tumours
      were excluded. RESULTS: Adrenal lesions were detected in 32 (8.4%) of 383
      patients included. The majority (22 patients - 69%) were located at the left
      adrenal gland and the mean size was 23.6 mm. In two patients, one with a well and
      another with a poorly differentiated tumour, clinicopathological features
      suggested adrenal metastases. During a mean follow-up period of 69.5 months, no
      subsequent growth of any adrenal lesion was observed. Endocrine evaluation
      documented subclinical glucocorticoid hypersecretion in 4 cases (14%). The
      presence of adrenal lesions did not correlate to distant metastases, however,
      they were observed more frequently in patients with G3 tumours. CONCLUSION: The
      prevalence of adrenal lesions in patients with GEP-NETs was found to be higher
      than the general population and mostly represent benign adrenal adenomas (except
      patients with G3 tumours). Nevertheless, individualized assessment of imaging
      characteristics should be still considered.

PMID- 22970734
TI  - Case of blastic plasmacytoid dendritic cell neoplasm.

PMID- 22970735
TI  - Influence of bentonite particles on representative gram negative and gram
      positive bacterial deposition in porous media.
AB  - The significance of clay particles on the transport and deposition kinetics of
      bacteria in irregular quartz sand was examined by direct comparison of both
      breakthrough curves and retained profiles with clay particles in bacteria
      suspension versus those without clay particles. Two representative cell types,
      Gram-negative strain E. coli DH5alpha and Gram-positive strain Bacillus subtilis
      were utilized to systematically determine the influence of clay particles
      (bentonite) on cell transport behavior. Packed column experiments for both cell
      types were conducted in both NaCl (5 and 25 mM ionic strengths) and CaCl(2) (5 mM
      ionic strength) solutions at pH 6.0. The breakthrough plateaus with bentonite in
      solutions (30 mg L(-1) and 50 mg L(-1)) were lower than those without bentonite
      for both cell types under all examined conditions, indicating that bentonite in
      solutions decreased cell transport in porous media regardless of cell types (Gram
      negative or Gram-positive) and solution chemistry (ionic strength and ion
      valence). The enhanced cell deposition with bentonite particles was mainly
      observed at segments near to column inlet, retained profiles for both cell types
      with bentonite particles were therefore steeper relative to those without
      bentonite. The increased cell deposition with bentonite observed in NaCl
      solutions was attributed to the codeposition of bacteria with bentonite particles
      whereas, in addition to codeposition of bacteria with bentonite, the bacteria
      bentonite-bacteria cluster formed in suspensions also contributed to the
      increased deposition of bacteria with bentonite in CaCl(2) solution.

PMID- 22970736
TI  - Highly variable insect control efficacy of Tephrosia vogelii chemotypes.
AB  - Tephrosia vogelii has been used for generations as a pest control material in
      Africa. Recently, two chemotypes have been reported based on the occurrence
      (chemotype 1) or absence (chemotype 2) of rotenoids. This could have an impact on
      the efficacy and reliability of this material for pest control. We report that
      chemotype 2 has no pesticidal activity against Callosobruchus maculatus Fabricius
      (family Chrysomelidae) and that this is associated with the absence of rotenoids.
      We present a first report of the comparative biological activity of deguelin,
      tephrosin, alpha-toxicarol, and sarcolobine and show that not all rotenoids are
      equally effective. Tephrosin was less toxic than deguelin which was less active
      than rotenone, while obovatin 5-methyl ether, the major flavonoid in chemotype 2
      was inactive. We also report that in chemotype 1 the occurrence of rotenoids
      shows substantial seasonal variation. 

PMID- 22970737
TI  - Effects on routine coagulation screens and assessment of anticoagulant intensity
      in patients taking oral dabigatran or rivaroxaban: guidance from the British
      Committee for Standards in Haematology.

PMID- 22970729
TI  - Specific metal recognition in nickel trafficking.
AB  - Nickel is an essential metal for a number of bacterial species that have
      developed systems for acquiring, delivering, and incorporating the metal into
      target enzymes and controlling the levels of nickel in cells to prevent toxic
      effects. As with other transition metals, these trafficking systems must be able
      to distinguish between the desired metal and other transition metal ions with
      similar physical and chemical properties. Because there are few enzymes (targets)
      that require nickel for activity (e.g., Escherichia coli transports nickel for
      hydrogenases made under anaerobic conditions, and Helicobacter pylori requires
      nickel for hydrogenase and urease that are essential for acid viability), the
      "traffic pattern" for nickel is relatively simple, and nickel trafficking
      therefore presents an opportunity to examine a system for the mechanisms that are
      used to distinguish nickel from other metals. In this review, we describe the
      details known for examples of uptake permeases, metallochaperones and proteins
      involved in metallocenter assembly, and nickel metalloregulators. We also
      illustrate a variety of mechanisms, including molecular recognition in the case
      of NikA protein and examples of allosteric regulation for HypA, NikR, and RcnR,
      employed to generate specific biological responses to nickel ions.

PMID- 22970738
TI  - Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5%
      eye drops in the management of ocular inflammation after cataract surgery.
AB  - PURPOSE: To determine whether indomethacin 0.1% eye drops are at least as
      effective as ketorolac 0.5% eye drops in treating ocular inflammation following
      cataract surgery. METHODS: Prospective, multicenter, investigator-masked,
      parallel-group, randomized, active-controlled clinical trial. Cataract patients
      were randomized in a 1:1 ratio to receive indomethacin or ketorolac administered
      QID for 3 weeks beginning 1 day before surgery. The primary end-point was aqueous
      flare measured by laser flare meter at postoperative Days 1 and 7. Secondary end
      points included retinal thickness, slit lamp and funduscopic examinations and
      postsurgical pain ratings. Safety and tolerability were also assessed. RESULTS: A
      total of 86 patients were included in the per protocol population (n = 43 per
      treatment group). Indomethacin was found non-inferior to ketorolac for comparison
      of aqueous flare at postoperative Days 1 and 7 (Day 1: 95% CI: -2.37, 5.50; non
      inferiority upper margin, 15 ph/ms and Day 7: 95% CI: -7.83, -0.94; non
      inferiority upper margin, 8 ph/ms) and statistically better than ketorolac at Day
      7 (p = 0.013). There were no significant between-group differences in aqueous
      flare and change from baseline in retinal thickness at postoperative Days 30 and
      90. Indomethacin showed a higher subjective tolerance rating than ketorolac at
      postoperative Days 7 and 30 (p <= 0.044). CONCLUSION: Indomethacin 0.1% was at
      least as effective as ketorolac 0.5% at Day 1 and more effective than ketorolac
      0.5% at Day 7 in treating ocular inflammation after uncomplicated cataract
      surgery. Indomethacin was better tolerated than ketorolac. There were no
      clinically meaningful safety concerns with either treatment.

PMID- 22970739
TI  - (I/O) hybrid alkoxysilane/zirconium-oxocluster copolymers as coatings for wood
      protection.
AB  - Novel inorganic-organic hybrid copolymers based on vinyl- or (3-mercaptopropyl)
      trimethoxysilane and an organically modified zirconium-oxocluster were
      investigated as a wood preservation treatment. The copolymers were prepared using
      a modified sol-gel strategy not involving alkoxysilane pre-hydrolysis and were
      applied on wood through a dip coating method. Even though the copolymers were
      mainly present on the surface of the wood, EDX analysis showed also a uniform
      distribution of silicon and zirconium in the cell wall but not in the lumina. The
      grafting of the copolymers on wood was confirmed through FTIR, (13)C and (29)Si
      MAS NMR analysis. The copolymer obtained from (3-mercaptopropyl)trimethoxysilane
      was post-functionalized with the methacrylic ester of thymol; introduced for
      testing as a biocide. Preliminary accelerated biological tests against the brown
      rot fungus Coniophora puteana, showed resistance to the fungus for the samples
      coated with the vinyltrimethoxysilane copolymer, while uneven results were
      obtained for the samples coated with the (3-mercaptopropyl)trimethoxysilane
      copolymer, even when functionalized with the ester of thymol.

PMID- 22970740
TI  - First record of the carmine spider mite, Tetranychus urticae, infesting Withania
      somnifera in India.
AB  - During April-June 2010, red two-spotted carmine spider mites Tetranychus urticae
      Koch (Trombidiformes: Tetranychidae) were found on aerial apical parts of
      Ashwagandha Withania somnifera (L.) Dunal (Solanales: Solanaceae) plants in the
      Amritsar District of Punjab Province in the North Indian plains. The mites fed on
      the leaves, making them shiny white in color, which gradually dried off and were
      later shed. The pest was identified as T. urticae. To best of our knowledge, this
      is the first record of this pest infesting W. somnifera in India.

PMID- 22970741
TI  - Pharmacokinetic evaluation and therapeutic activity of  bendamustine  in B-cell
      lymphoid malignancies.
AB  - INTRODUCTION: Bendamustine , a cytotoxic agent comprising structural features of
      both an alkylating drug and a purine nucleoside analog, was approved by the US
      FDA for treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non
      Hodgkin's lymphoma (NHL). Additionally, in Europe the drug has been also approved
      for treatment of multiple myeloma (MM) and in Asia, especially in Japan for
      refractory/relapsed NHL and mantle cell lymphoma. AREAS COVERED: The authors
      present the chemical structure, mechanism of action, pharmacokinetic properties
      and clinical application of bendamustine in hematological malignancies.
      Publications in English related to the above, up to June 2012, have been surveyed
      in the MEDLINE database. Conference proceedings reports from the last 5 years are
      also included. Additional relevant publications have been obtained by reviewing
      the references from the chosen articles. EXPERT OPINION: The availability of
      bendamustine provides an effective treatment option for patients with lymphoid
      malignancies. Several recent clinical trials have documented the activity of
      bendamustine in CLL, NHL and MM, both as a single agent and in combination with
      other cytotoxic drugs. However, doses, schedules and also the role of
      bendamustine in treatment of patients with hematological malignancies should be
      further investigated to establish its real place in the management of these
      diseases.

PMID- 22970742
TI  - Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing
      zinc pyrithione and climbazole.
AB  - Dandruff is a common complaint and is suffered by as much as half of the
      population at some time post puberty. The condition is characterized by the
      presence of flakes on the scalp and in the hair, and is often accompanied by
      itch. The most common treatment for dandruff is the use of shampoo formulations
      that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox.
      Whilst most antidandruff shampoos are effective in resolving the symptoms of
      dandruff these shampoos can often result in hair condition that is less than
      acceptable to consumers which can lead to a tendency for them to revert to use of
      a non-antidandruff shampoo. This can result in a rapid return of dandruff
      symptoms. The aim of this investigation was to study the impact of using a
      combination of antidandruff actives and silicones on the resolution of dandruff
      and to deliver superior sensory properties to the hair. We have demonstrated that
      shampoo containing the dual active system of ZPT/Climbazole deposits both active
      agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur
      regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated
      superior efficacy and retained superiority during a regression phase where all
      subjects reverted to using a non-antidandruff shampoo. We have also demonstrated
      that it is possible to deposit silicone materials from antidandruff shampoo
      uniformly over both virgin and damaged hair fibres that results in smoother hair
      fibres (as evidenced by reduced dry friction). This combination of antidandruff
      agents and conditioning silicones delivered from a shampoo provides subjects with
      superior antidandruff efficacy and desired end sensory benefits ensuring
      compliance and longer term dandruff removal.

PMID- 22970743
TI  - Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of
      the literature.
AB  - BACKGROUNDS AND AIMS: Organ shortage is a major problem in transplantation. The
      use of organs from hepatitis B surface antigen (HBsAg)-negative and hepatitis B
      core antibody (HBcAb)-positive donors could significantly increase the donor
      pool. However, little information is available about the impact of HBcAb status
      of renal donors on viral transmission to recipients. To address this issue, the
      present quantitative review of relevant studies has been performed. MATERIALS AND
      METHODS: Electronic databases including Medline, EMBASE, ISI, and Scopus were
      systematically searched for studies that evaluated risk of hepatitis B virus
      (HBV) transmission through renal transplantation from HBsAg-/HBcAb+ donors.
      Eligible studies were identified according to predefined criteria. The final
      outcome was one of HBV markers seroconversion defined as HBsAg, hepatitis B
      surface antibody (HBsAb), or HBcAb detection in previously seronegative end-stage
      renal disease (ESRD) patients after transplantation, and without other identified
      major sources of infection. RESULTS: Nine studies with 1385 eligible kidney
      recipients were included. In total, 45 subjects showed seroconversion of HBV
      markers as follows: HBsAg (n = 4) (0.28%; 95% confidence interval [CI] 0.006;
      0.57), HBcAb (n = 32), HBsAb (n = 5), and either HBcAb or HBsAb (n = 4). The
      total rate of seroconversion after renal transplantation was calculated to be
      3.24% (95% CI: 2.31-4.18). CONCLUSION: Our review indicates that the risk of HBV
      transmission from HBcAb-positive kidney donors is extremely low. Therefore,
      kidneys from these donors can be transplanted safely into ESRD patients.

PMID- 22970744
TI  - Effect of bone morphogenetic protein-2, demineralized bone matrix and systemic
      parathyroid hormone (1-34) on local bone formation in a rat calvaria critical
      size defect model.
AB  - AIM: To determine the potential of recombinant human bone morphogenetic protein-2
      (rhBMP-2) soak-loaded on to an absorbable collagen sponge (ACS) to induce local
      bone formation compared with the clinical reference demineralized bone matrix
      (DBM) and to investigate potential additive/synergistic effects of exogenous
      parathyroid hormone (PTH). METHODS: Critical-size (8 mm), through-through
      calvaria osteotomy defects in 160 adult male Sprague-Dawley rats were randomized
      to receive one of eight interventions: rhBMP-2/ACS, DBM, ACS, or serve as
      controls (empty defects) combined or not with systemic PTH. Ten animals from each
      group were followed for 4 and 8 wks for radiographic and histometric analysis.
      Multivariable analysis was used to assess the effect of experimental intervention
      and healing time on local bone formation. RESULTS: In the multivariable analysis,
      rhBMP-2/ACS exhibited significantly greater histologic bone formation than
      control (beta +/- SE: 54.76 +/- 5.85, p < 0.001) and ACS (beta +/- SE: 9.14 +/-
      3.31, p = 0.007) whereas DBM showed significantly less bone formation than
      control (beta +/- SE: -32.32 +/- 8.23, p < 0.001). Overall, PTH did not show a
      significant effect on bone formation (beta +/- SE: 2.72 +/- 6.91, p = 0.70). No
      significant differences in histological defect closure were observed between 4
      and 8 wks for all but the control group without PTH. CONCLUSION: rhBMP-2/ACS
      significantly stimulates local bone formation whereas bone formation appears
      significantly limited by DBM. Systemic application of PTH provided no discernible
      additive/synergistic effects on local bone formation.

PMID- 22970745
TI  - Supramolecular ordering of PTCDA molecules: the key role of dispersion forces in
      an unusual transition from physisorbed into chemisorbed state.
AB  - Adsorption and self-assembly of large pi-conjugated 3,4,9,10-perylene
      tetracarboxylic dianhydride (PTCDA) molecules on rutile TiO(2)(110) surface have
      been investigated using a combination of high-resolution scanning tunneling
      microscopy (STM), low-energy electron diffraction, and density functional theory
      calculations with inclusion of Grimme treatment of the dispersion forces (DFT-D).
      Evolution of the STM images as a function of PTCDA coverage is caused by
      transition of the adsorption mode from physisorbed single adspecies and
      meandering stripes into spontaneously ordered chemisorbed molecular assemblies.
      This change in the adsorption fashion is accompanied by significant bending of
      the intrinsically flat, yet elastic, PTCDA molecule, which allows for strong
      electronic coupling of the dye adspecies with the TiO(2) substrate. Extensive DFT
      D modeling has revealed that adsorption is controlled by interfacial and
      intermolecular dispersion forces playing a dominant role in the adsorption of
      single PTCDA species, their self-organization into the meandering stripes, and at
      the monolayer coverage acting collectively to surmount the chemisorption energy
      barrier associated with the molecule bending. Analysis of the resulting density
      of states has revealed that alignment of the energy levels and strong electronic
      coupling at the PTCDA/TiO(2) interface are beneficial for dye sensitization
      purposes.

PMID- 22970746
TI  - Binding geometry of hydrogen-bonded chain motif in self-assembled gratings and
      layers on Ag(111).
AB  - Upon adsorption on the (111) facet of Ag, 4-[trans-2-(pyrid-4-yl-vinyl)] benzoic
      acid (PVBA) self-assembles into a highly ordered, chiral twin chain structure at
      submonolayer coverages with domains that can extend for micrometers in one
      dimension. Using polarization-dependent measurements of C and N K-shell
      excitations in near-edge X-ray absorption fine structure (NEXAFS) spectra, we
      determine the binding geometry of single PVBA molecules within this unique
      ensemble for both low and high coverage regimes. At submonolayer coverage, the
      molecule is twisted to facilitate the formation of hydrogen bonds. The gas-phase
      planarity is gradually recovered as the coverage is increased, with complete
      planarity coinciding with loss of order in the overlayer. Thermal treatment of
      the PVBA film results in deprotonation of the carboxyl tail of the molecule, but
      despite the suppression of the stabilizing hydrogen-bonds, the overlayer remains
      ordered.

PMID- 22970747
TI  - Can asthma education improve the treatment of acute asthma exacerbation in young
      children?
AB  - Acute exacerbation of asthma requires timely and appropriate treatment. Young
      children are completely reliant on others in this respect. This paper aims to
      evaluate the effectiveness of staff asthma education programs in ensuring correct
      treatment for young children experiencing asthma exacerbations in formal care. A
      systematic review was undertaken of studies focusing on staff asthma education in
      relation to pharmacological treatment of acute asthma exacerbation. Three
      randomised controlled trials and seven uncontrolled pre- and post-test
      intervention studies were included for review. Asthma education was found to
      increase staff knowledge and confidence in managing asthma. There was a distinct
      lack of staff performance testing and studies undertaken in the pre-school
      setting. Staff asthma education appears effective in increasing asthma knowledge;
      however, utility of this measure is limited with respect to staff performance in
      treating acute asthma exacerbation. Further studies evaluating asthma education
      through performance are needed.

PMID- 22970748
TI  - Editorial.

PMID- 22970749
TI  - Four-component cascade heteroannulation of heterocyclic ketene aminals: synthesis
      of functionalized tetrahydroimidazo[1,2-a]pyridine derivatives.
AB  - An efficient and straightforward four-component synthetic protocol has been
      developed to synthesize imidazo[1,2-a]pyridines and imidazo[1,2,3
      ij][1,8]naphthyridine derivatives incorporating medicinally privileged
      heterosystems from heterocyclic ketene aminals, aldehydes, diketene, and amines
      via cascade reactions, including diketene ring-opening, Knoevenagel condensation,
      aza-ene reaction, imine-enamine tautomerization, cyclocondensation, and
      intramolecular S(N)Ar. This strategy can provide an alternative approach for easy
      access to the highly substituted imidazo[1,2-a]pyridine derivatives in moderate
      to good yields using four simple and readily available building blocks under mild
      conditions. Importantly, the unusual splitting peaks in the (1)H NMR spectra of
      the products derived from heterocyclic ketene aminals with an o-halogen atom on
      the aryl ring were explained reasonably by varying the temperature in NMR
      analysis.

PMID- 22970750
TI  - Application of whey protein micro-bead coatings for enhanced strength and
      probiotic protection during fruit juice storage and gastric incubation.
AB  - CONTEXT: Coated whey protein micro-beads may improve probiotic protection and
      provide delayed cell-release mechanisms. OBJECTIVE: Lactobacillus rhamnosus GG
      was encapsulated in whey protein micro-beads by droplet extrusion with coating
      via electrostatic deposition: primary-polysaccharide and secondary-whey protein.
      MATERIALS AND METHODS: Storage studies were performed in cranberry and
      pomegranate juice (pH 2.4; 28 days; 4 and 25 degrees C) followed by simulated ex
      vivo porcine gastric (pH 1.6) and intestinal (pH 6.6) digestion. RESULTS AND
      DISCUSSION: After storage and simulated gastro-intestinal digestion, free cells,
      cells suspended in protein and cells encapsulated in alginate micro-beads,
      illustrated complete probiotic mortality, while coated micro-beads enhanced
      probiotic viability after juice storage (8.6 +/- 0.1 log(10)CFUmL(-1)). Beads
      also showed significant binding of hydrophobic molecules. Coated micro-beads
      illustrated high gastric survival (9.5 +/- 0.1 log(10)CFUmL(-1)) with 30 min
      delayed intestinal release relative to non-coated micro-beads. CONCLUSIONS: Micro
      bead coatings could be applied in delayed cell-release for targeted intestinal
      probiotic delivery.

PMID- 22970751
TI  - Distalization pattern of the maxillary arch depending on the number of
      orthodontic miniscrews.
AB  - OBJECTIVE: To determine the effects of linear force vector(s) from interradicular
      miniscrews on the distalization pattern of the maxillary arch in adult Class II
      patients. MATERIALS AND METHODS: Twenty-five adult patients with mild to moderate
      Class II dentition and minimal crowding were collected. Either single (group A, n
      =  12) or dual (group B, n  =  13) miniscrews were inserted on the posterior
      interradicular area to deliver a distalizing force to the main archwire. The
      displacement patterns of maxillary incisors and molars were measured and
      compared. RESULTS:   Significant distalization in the molars and incisors was
      shown in both groups. Significantly greater distalization and intrusion of the
      first molar and intrusive displacement of the incisor, together with significant
      reduction of the mandibular plane, were noted in group B, in contrast to the
      rotation of the occlusal plane in group A. CONCLUSIONS: Interradicular miniscrews
      predictably induced total arch distalization, leading to the correction of Class
      II. Additional miniscrews in the premolar area appear to facilitate intrusion and
      distalization of the entire arch according to the position of the force vectors.

PMID- 22970752
TI  - Biomechanical validation of an artificial tooth-periodontal ligament-bone complex
      for in vitro orthodontic load measurement.
AB  - OBJECTIVES: To develop an artificial tooth-periodontal ligament (PDL)-bone
      complex (ATPBC) that simulates clinical crown displacement. MATERIAL AND METHODS:
      An ATPBC was created. It had a socket hosting a tooth with a thin layer of
      silicon mixture in between for simulating the PDL. The complex was attached to a
      device that allows applying a controlled force to the crown and measuring the
      resulting crown displacement. Crown displacements were compared to previously
      published data for validation. RESULTS: The ATPBC that had a PDL made of two
      types of silicones, 50% gasket sealant No. 2 and 50% RTV 587 silicone, with a
      thickness of 0.3 mm, simulated the PDL well. The mechanical behaviors (1) force
      displacement relationship, (2) stress relaxation, (3) creep, and (4) hysteresis
      were validated by the published results. CONCLUSION: The ATPBC simulated the
      crown displacement behavior reported from biological studies well.

PMID- 22970756
TI  - Abstracts of the British Equine Veterinary Association Congress 2012. September
      12-15, 2012. Birmingham, United Kingdom.

PMID- 22970753
TI  - Quality of cardiovascular disease care in Ontario, Canada: missed opportunities
      for prevention - a cross sectional study.
AB  - BACKGROUND: Primary care plays a key role in the prevention and management of
      cardiovascular disease (CVD). We examined primary care practice adherence to
      recommended care guidelines associated with the prevention and management of CVD
      for high risk patients. METHODS: We conducted a secondary analysis of cross
      sectional baseline data collected from 84 primary care practices participating in
      a large quality improvement initiative in Eastern Ontario from 2008 to 2010. We
      collected medical chart data from 4,931 patients who either had, or were at high
      risk of developing CVD to study adherence rates to recommended guidelines for CVD
      care and to examine the proportion of patients at target for clinical markers
      such as blood pressure, lipid levels and hemoglobin A1c. RESULTS: Adherence to
      preventive care recommendations was poor. Less than 10% of high risk patients
      received a waistline measurement, half of the smokers received cessation advice,
      and 7.7% were referred to a smoking cessation program. Gaps in care exist for
      diabetes and kidney disease as 54.9% of patients with diabetes received
      recommended hemoglobin-A1c screenings, and only 55.8% received an albumin
      excretion test. Adherence rates to recommended guidelines for coronary artery
      disease, hypertension, and dyslipidemia were high (>75%); however <50% of
      patients were at target for blood pressure or LDL-cholesterol levels (37.1% and
      49.7% respectively), and only 59.3% of patients with diabetes were at target for
      hemoglobin-A1c. CONCLUSIONS: There remain significant opportunities for primary
      care providers to engage high risk patients in prevention activities such as
      weight management and smoking cessation. Despite high adherence rates for
      hypertension, dyslipidemia, and coronary artery disease, a significant proportion
      of patients failed to meet treatment targets, highlighting the complexity of
      caring for people with multiple chronic conditions.

PMID- 22970758
TI  - Functional screening of pharmacological chaperones via restoration of enzyme
      activity upon denaturation.
AB  - Pharmacological chaperones (PCs) are small molecules that stabilize and promote
      protein folding. Enzyme inhibition is widely used for PC selection; however, it
      does not accurately reflect chaperone activity. We introduce a functional assay
      for characterization of PCs based on their capacity to restore enzyme activity
      that is abolished upon chemical denaturation. Dose-dependent activity curves were
      performed as a function of urea to assess the chaperone potency of various
      ligands to beta-glucocerebrosidase as a model system. Restoration of enzyme
      activity upon denaturation allows direct screening of PCs for treatment of
      genetic disorders associated with protein deficiency, such as Gaucher disease.

PMID- 22970760
TI  - Fe(II)-mediated reduction and repartitioning of structurally incorporated Cu, Co,
      and Mn in iron oxides.
AB  - The reduction of trace elements and contaminants by Fe(II) at Fe(III) oxide
      surfaces is well documented. However, the effect of aqueous Fe(II) on the fate of
      redox-active trace elements structurally incorporated into iron oxides is
      unknown. Here, we investigate the fate of redox-active elements during Fe(II)
      activated recrystallization of Cu-, Co-, and Mn-substituted goethite and
      hematite. Enhanced release of Cu, Co, and Mn to solution occurs upon exposure of
      all materials to aqueous Fe(II) relative to reactions in Fe(II)-free fluids. The
      quantity of trace element release increases with pH when Fe(II) is present but
      decreases with increasing pH in the absence of Fe(II). Co and Mn release from
      goethite is predicted well using a second-order kinetic model, consistent with
      the release of redox-inactive elements such as Ni and Zn. However, Cu release and
      Co and Mn release from hematite require the sum of two rates to adequately model
      the kinetic data. Greater uptake of Fe(II) by Cu-, Co-, and Mn-substituted iron
      oxides relative to analogues containing only redox-inactive elements suggests
      that net Fe(II) oxidation occurs. Reduction of Cu, Co, and Mn in all materials
      following reaction with Fe(II) at pHs 7.0-7.5 is confirmed by X-ray absorption
      near-edge structure spectroscopy. This work shows that redox-sensitive elements
      structurally incorporated within iron oxides are reduced and repartitioned into
      fluids during Fe(II)-mediated recrystallization. Such abiotic reactions likely
      operate in tandem with partial microbial and abiotic iron reduction or during the
      migration of Fe(II)-containing fluids, mobilizing structurally bound contaminants
      and micronutrients in aquatic systems.

PMID- 22970759
TI  - Structure of WbdD: a bifunctional kinase and methyltransferase that regulates the
      chain length of the O antigen in Escherichia coli O9a.
AB  - The Escherichia coli serotype O9a O-antigen polysaccharide (O-PS) is a model for
      glycan biosynthesis and export by the ATP-binding cassette transporter-dependent
      pathway. The polymannose O9a O-PS is synthesized as a polyprenol-linked glycan by
      mannosyltransferase enzymes located at the cytoplasmic membrane. The chain length
      of the O9a O-PS is tightly regulated by the WbdD enzyme. WbdD first
      phosphorylates the terminal non-reducing mannose of the O-PS and then methylates
      the phosphate, stopping polymerization. The 2.2 A resolution structure of WbdD
      reveals a bacterial methyltransferase domain joined to a eukaryotic kinase
      domain. The kinase domain is again fused to an extended C-terminal coiled-coil
      domain reminiscent of eukaryotic DMPK (Myotonic Dystrophy Protein Kinase) family
      kinases such as Rho-associated protein kinase (ROCK). WbdD phosphorylates 2-alpha
      d-mannosyl-d-mannose (2alpha-MB), a short mimic of the O9a polymer. Mutagenesis
      identifies those residues important in catalysis and substrate recognition and
      the in vivo phenotypes of these mutants are used to dissect the termination
      reaction. We have determined the structures of co-complexes of WbdD with two
      known eukaryotic protein kinase inhibitors. Although these are potent inhibitors
      in vitro, they do not show any in vivo activity. The structures reveal new
      insight into O-PS chain-length regulation in this important model system.

PMID- 22970762
TI  - Use of haloperidol in PCP-intoxicated individuals.
AB  - CONTEXT: Emergency medical workers often experience violence while performing
      their job functions. Phencyclidine (PCP)-intoxicated patients are often violent
      and difficult to control physically. A chemical restraint is frequently needed to
      assist in protecting both patients and staff from agitated persons. OBJECTIVE:
      This study evaluated haloperidol as a chemical restraint in PCP-intoxicated
      patients. METHODS: This is a retrospective case series of all PCP-positive
      patients who received haloperidol for behavioral control from April 2008 to April
      2011 at a single large (944 bed), urban, tertiary-care hospital. All patients
      receiving haloperidol and having a toxicology screen positive for PCP were
      identified using an electronic medical record. Identified cases were then
      manually reviewed by investigators for adverse events. RESULTS: Subjects included
      59 adult patients who were acutely agitated requiring chemical restraint or
      sedation with haloperidol, and who tested positive for PCP. There were 20 females
      and 39 males, ranging in age from 19 to 54 years. Patients received haloperidol
      via the PO, IM, or IV routes in doses ranging from 1 to 10 mg. There were two
      adverse events (mild hypoxia and mild hypotension) found during chart review;
      neither were serious nor required change in patient disposition. CONCLUSIONS: In
      this study, haloperidol does not seem to cause harm when used in the management
      of PCP-intoxicated patients. Caution must always be exercised in the use of
      chemical restraint; further prospective study is warranted.

PMID- 22970761
TI  - Immune system polymorphisms and factor VIII inhibitor formation in Brazilian
      haemophilia A severe patients.

PMID- 22970763
TI  - Public versus private treatment of chronic diseases in seniors: Argentina,
      Brazil, Chile and Uruguay.
AB  - This article measures differences in the likelihood of treatment of chronic
      diseases in elders across types of coverage (private, public and social security)
      in four major Latin American cities: Buenos Aires (Argentina), Sao Paulo
      (Brazil), Santiago (Chile) and Montevideo (Uruguay). We used a logistic
      regression to estimate the odds ratio for treatment of chronic diseases carried
      by individuals with public, private and social security coverage. The data were
      from the Survey on health, well-being and aging in Latin America and the
      Caribbean (SABE) conducted in 1999 and 2000. We find a strong association between
      possession of public coverage only and treatment failure of chronic diseases in
      elders in Argentina. We find no significant association for Brazil, Chile and
      Uruguay. In Buenos Aires, access to private or social security coverage is a
      necessity for elders because the public sector fails to provide proper treatment.
      In the remaining cities, private or social security coverage provides similar
      coverage for chronic diseases in elders compared with the public sector. For this
      group of countries, the main difference between the former and the latter seems
      to be in terms of 'luxurious' characteristics, such as the quality of the
      facilities and waiting times.

PMID- 22970765
TI  - A reaction-based fluorescent probe for selective imaging of carbon monoxide in
      living cells using a palladium-mediated carbonylation.
AB  - Carbon monoxide is a member of the gasotransmitter family, which also includes NO
      and H(2)S, and has been implicated in a variety of pathological and physiological
      conditions. Whereas exogenous therapeutic additions of CO to tissues and whole
      animals have been well-studied, the real-time spatial and temporal tracking of CO
      at the cellular level remains an open challenge. Here we report a new type of
      turn-on fluorescent probe for selective CO detection based on palladium-mediated
      carbonylation reactivity. CO Probe 1 (COP-1) is capable of detecting CO both in
      aqueous buffer and in live cells with high selectivity over a range of
      biologically relevant reactive small molecules, providing a potentially powerful
      approach for interrogating its chemistry in biological systems.

PMID- 22970764
TI  - The relationship between quality of work life and turnover intention of primary
      health care nurses in Saudi Arabia.
AB  - BACKGROUND: Quality of work life (QWL) has been found to influence the commitment
      of health professionals, including nurses. However, reliable information on QWL
      and turnover intention of primary health care (PHC) nurses is limited. The aim of
      this study was to examine the relationship between QWL and turnover intention of
      PHC nurses in Saudi Arabia. METHODS: A cross-sectional survey was used in this
      study. Data were collected using Brooks' survey of Quality of Nursing Work Life,
      the Anticipated Turnover Scale and demographic data questions. A total of 508 PHC
      nurses in the Jazan Region, Saudi Arabia, completed the questionnaire (RR = 87%).
      Descriptive statistics, t-test, ANOVA, General Linear Model (GLM) univariate
      analysis, standard multiple regression, and hierarchical multiple regression were
      applied for analysis using SPSS v17 for Windows. RESULTS: Findings suggested that
      the respondents were dissatisfied with their work life, with almost 40%
      indicating a turnover intention from their current PHC centres. Turnover
      intention was significantly related to QWL. Using standard multiple regression,
      26% of the variance in turnover intention was explained by QWL, p < 0.001, with
      R2 = .263. Further analysis using hierarchical multiple regression found that the
      total variance explained by the model as a whole (demographics and QWL) was
      32.1%, p < 0.001. QWL explained an additional 19% of the variance in turnover
      intention, after controlling for demographic variables. CONCLUSIONS: Creating and
      maintaining a healthy work life for PHC nurses is very important to improve their
      work satisfaction, reduce turnover, enhance productivity and improve nursing care
      outcomes.

PMID- 22970766
TI  - Detection of the far-IR nu12 bending level in propargyl: a complete set of
      fundamentals for an important radical.
AB  - Propargyl (HCCCH(2)) radicals have been generated by expanding precursors through
      a supersonic pyrolysis nozzle, and their infrared (IR) absorption spectra have
      been recorded in a rare gas matrix. Besides the 10 vibrational modes observed in
      our previous studies, this investigation detected the HCCCH(2) X (2)B(1) in-plane
      bending mode (nu(12)) at 344.2 (+/-0.8) cm(-1) in a cryogenic argon matrix. This
      is the first experimental observation of nu(12) for the propargyl radical. In the
      previous study, nu(12) had been fixed at 333 (+/-10) cm(-1) based on detection of
      its overtone (2nu(12), 667.7 +/- 1.0 cm(-1)) and a possible combination band
      (nu(10) + nu(12), 1339.0 +/- 0.8 cm(-1)). The new observation is in reasonable
      agreement with this previous experimental estimation of nu(12). Ab initio coupled
      cluster anharmonic force field calculations were used to guide the analysis. Our
      finding completes the fundamental frequency database for propargyl.

PMID- 22970767
TI  - Standard operating procedures in the disorders of orgasm and ejaculation.
AB  - INTRODUCTION: Ejaculatory/orgasmic disorders are common male sexual dysfunctions
      and include premature ejaculation (PE), inhibited ejaculation, anejaculation,
      retrograde ejaculation, and anorgasmia. AIM: To provide recommendations and
      guidelines of the current state-of-the-art knowledge for management of
      ejaculation/orgasmic disorders in men as standard operating procedures (SOPs) for
      the treating health care professional. METHODS: The International Society of
      Sexual Medicine Standards Committee assembled over 30 multidisciplinary experts
      to establish SOPs for various male and female sexual medicine topics. The SOP for
      the management of disorders of orgasm and ejaculation represents the opinion of
      four experts from four countries developed in a process over a 2-year period.
      MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based
      medical literature, limited expert opinion, widespread internal committee
      discussion, public presentation, and debate. RESULTS: PE management is largely
      dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy
      (selective serotonin reuptake inhibitors and/or topical anesthetics). The
      management of acquired PE is etiology specific and may include erectile
      dysfunction (ED) pharmacotherapy in men with comorbid ED. All men seeking
      treatment for PE should receive basic psychosexual education. Graded behavioral
      therapy is indicated when psychogenic or relationship factors are present and is
      often best combined with PE pharmacotherapy in an integrated treatment program.
      Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or
      psychogenic etiology. Men with age-related penile hypoanesthesia should be
      educated, reassured, and instructed in revised sexual techniques which maximize
      arousal. Retrograde ejaculation is managed by education, patient reassurance, and
      pharmacotherapy. CONCLUSIONS: Additional research is required to further the
      understanding of the disorders of ejaculation and orgasm.

PMID- 22970768
TI  - Sudden cardiac death as the presentation of acute myeloid leukaemia.

PMID- 22970770
TI  - Verification of aroma profiles of Jiashi muskmelon juice characterized by odor
      activity value and gas chromatography-olfactometry/detection frequency analysis:
      aroma reconstitution experiments and omission tests.
AB  - To verify the aroma profile of Jiashi muskmelon previously identified by gas
      chromatography-olfactometry/detection frequency analysis (GC-O/DFA) and odor
      activity value (OAV) calculation, the synthetic blends of odorants (aroma models)
      were prepared and then were compared with the original Jiashi muskmelon juice
      aroma using quantitative descriptive analysis (QDA) and electronic nose analysis
      (ENA), respectively. QDA and ENA both indicated that the model solution derived
      from OAV calculation more closely resembled the original melon juice aroma than
      that based on DFA data. Omission tests corroborated the significant contribution
      of five unsaturated aldehydes and alcohols with nine carbon atoms as well as five
      branched esters, in particular, the "fruity"-smelling ethyl butanoate and the
      "cucumber-like" (2E,6Z)-nona-2,6-dienal to Jiashi muskmelon overall aroma.

PMID- 22970769
TI  - Anti-gal antibodies in alpha1,3-galactosyltransferase gene-knockout pigs.
AB  - Serum anti-galactose-alpha1,3-galactose (Gal) IgM and IgG antibody levels were
      measured by ELISA in alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs (78
      estimations in 47 pigs). A low level of anti-Gal IgM was present soon after
      birth, and rose to a peak at 4-6 m, which was maintained thereafter even in the
      oldest pigs tested (at >2 yr). Anti-Gal IgG was also present at birth, peaked at
      3 m, and after 6 m steadily decreased until almost undetectable at 20 m. No
      differences in this pattern were seen between pigs of different gender. Total IgM
      followed a similar pattern as anti-Gal IgM, but total IgG did not decrease after
      6m. The data provide useful baseline data for future experimental studies in GTKO
      pigs, e.g., relating to the antibody response to WT pig allografts.

PMID- 22970771
TI  - External dacryocystorhinostomy in Wegener's granulomatosis.

PMID- 22970773
TI  - Effects of topographical and mechanical property alterations induced by oxygen
      plasma modification on stem cell behavior.
AB  - Polymeric substrates intended for cell culture and tissue engineering are often
      surface-modified to facilitate cell attachment of most anchorage-dependent cell
      types. The modification alters the surface chemistry and possibly topography.
      However, scant attention has been paid to other surface property alterations. In
      studying oxygen plasma treatment of polydimethylsiloxane (PDMS), we show that
      oxygen plasma treatment alters the surface chemistry and, consequently, the
      topography and elasticity of PDMS at the nanoscale level. The elasticity factor
      has the predominant effect, compared with the chemical and topographical factors,
      on cell adhesions of human mesenchymal stem cells (hMSCs). The enhanced focal
      adhesions favor cell spreading and osteogenesis of hMSCs. Given the prevalent use
      of PDMS in biomedical device construction and cell culture experiments, this
      study highlights the importance of understanding how oxygen plasma treatment
      would impact subsequent cell-substrate interactions. It helps explain
      inconsistency in the literature and guides preparation of PDMS-based biomedical
      devices in the future.

PMID- 22970772
TI  - Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs.
AB  - INTRODUCTION: Antimicrobial drugs are essential in the treatment of infectious
      diseases. A better understanding of transport processes involved in drug
      disposition will improve the predictability of drug-drug interactions with
      consequences for drug response. Multidrug And Toxin Extrusion (MATE; SLC47A)
      proteins are efflux transporters mediating the excretion of several antimicrobial
      drugs as well as other organic compounds into bile and urine, thereby
      contributing to drug disposition. AREAS COVERED: This review summarizes current
      knowledge of the structural and molecular features of human MATE transporters
      including their functional role in drug transport with a specific focus on
      antimicrobial drugs. The PubMed database was searched using the terms "MATE1,"
      "MATE-2K," "MATE2," "SLC47A1," "SLC47A2," and "toxin extrusion protein" (up to
      June 2012). EXPERT OPINION: MATE proteins have been recognized as important
      transporters mediating the final excretion step of cationic drugs into bile and
      urine. These include the antiviral drugs acyclovir, amprenavir, and ganciclovir,
      the antibiotics cephalexin, cephradine and levofloxacin, as well as the
      antimalarial agents chloroquine and quinine. It is therefore important to enhance
      our understanding of the role of MATEs in drug extrusion with particular emphasis
      on the functional consequences of genetic variants on disposition of these
      antimicrobial drugs.

PMID- 22970774
TI  - The potential role of proinflammatory and antiinflammatory cytokines in Alzheimer
      disease pathogenesis.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      destructive alterations of neurons (neurofibrillary tangles and amyloid plaques),
      and cognitive impairment. Inflammation is a key pathological hallmark of AD, thus
      the clinical and immunopathological evidence could be supported by potential role
      of inflammatory cytokines in AD, which may actively contribute to disease
      progression and chronicity. However, their effects in disease progression and
      neurodegeneration remain an area of investigation. This review article provides
      an overview of pro- and anti-inflammatory cytokine activity in AD.

PMID- 22970775
TI  - Counseling on Early Childhood Caries transmission by dentists.
AB  - OBJECTIVE: High levels of Streptococcus mutans on teeth of young children are
      predictive of Early Childhood Caries (ECC). Transmission from mother-to-child is
      common and studies have demonstrated treatment of the mother results in less ECC.
      The objective of this study was to determine how dentists have adopted the
      practice of counseling about ECC. METHODS: In 2006 as part of a larger study on
      dental care for pregnant women, we surveyed 829 general dentists in Oregon. The
      questionnaire contained questions to capture the extent to which general dentists
      have adopted counseling pregnant women about ECC transmission, to describe
      personal and practice characteristics, and examine how dentists' views on the
      ease of adopting of new procedures related to ECC counseling. Multivariate
      logistic regression was used to identify separate and additive effects of
      demographic and practice characteristics, attitudes, and beliefs. RESULTS: The
      adjusted odds of a dentist who strongly believed in the link between mothers and
      babies and provided ECC counseling were 1.60 (95% CI 1.3-2.0, P<0.01). The odds
      of a dentist who reported discussing ECC with staff members and provided
      counseling were 2.7 (95% CI 1.7-4.3, P<0.01). Male dentists were less likely to
      counsel patients than female dentists (Adjusted OR=0.5, 95% CI 0.3-1.0, p<0.05).
      CONCLUSIONS: The strongest predictors of counseling patients about ECC were
      dentists' belief in the evidence of caries transmission and dentists' discussion
      of ECC during staff meetings.

PMID- 22970776
TI  - Persistent unilateral white-out in preterm infant.
AB  - We would like to present a case of persistent right sided collapse in a preterm
      baby with an unexpected diagnosis. Baby X was born floppy requiring resuscitation
      and was intubated, ventilated and was transferred to NICU. There was decreased
      air entry on auscultation of right side of the chest, while the rest of the
      examination was normal. The chest X-ray showed right side white-out suggestive of
      collapse consolidation. She required significantly high ventilatory pressures to
      maintain saturations and chest X-ray performed on day 4 remained unchanged with
      persistent right sided white-out. The CT scan of the chest showed no definable
      right lung, right pulmonary artery or right main bronchus. The diagnosis of right
      lung agenesis with single pulmonary artery was made and baby was found to have
      more congenital malformations on further investigations, and later developed
      complications leading to palliative care.

PMID- 22970777
TI  - Relationship between perceived softness of bilayered skin models and their
      mechanical properties measured with a dual-sensor probe.
AB  - The development of a sensor system that can predict the subjective softness of
      human skin is an important goal for the cosmetics industry. Here, we first
      carried out a subjective softness evaluation test using 65 skin models consisting
      of polyurethane bilayers with different thickness of the superficial layer and
      different degree of cross-polymerization of the basal layer. The results showed
      that perceived softness was dependent on the mechanical properties of both the
      superficial and basal layers. Then, we used a recently developed tactile sensor
      system composed of a piezoelectric tactile sensor and a load cell to measure
      mechanical softness parameters of the superficial layer and the whole model,
      respectively. Statistical analysis showed that the data obtained from these two
      sensors were well correlated with the perceived softness of the prepared models.
      These results suggest that it may be feasible to predict the subjective softness
      of human skin in vivo from non-invasive mechanical softness measurements of the
      superficial skin layer and whole skin obtained with our new dual-probe sensor
      system.

PMID- 22970778
TI  - A chemical route to increase hot spots on silver nanowires for surface-enhanced
      Raman spectroscopy application.
AB  - The effective number of surface-enhanced Raman spectroscopy (SERS) active hot
      spots on plasmonic nanostructures is the most crucial factor in ensuring high
      sensitivity in SERS sensing platform. Here we demonstrate a chemical etching
      method to increase the surface roughness of one-dimensional Ag nanowires,
      targeted at creating more SERS active hot spots along Ag nanowire's longitudinal
      axis for increased SERS detection sensitivity. Silver nanowires were first
      synthesized by the conventional polyol method and then subjected to chemical
      etching by NH(4)OH and H(2)O(2) mixture. The surfaces of silver nanowires were
      anisotropically etched off to create miniature "beads on a string" features with
      increased surface roughness while their crystallinity was preserved. Mapping of
      single-nanowire SERS measurements showed that the chemical etching method has
      overcome the limitation of conventional one-dimensional Ag nanowires with limited
      SERS active area at the tips to produce etched Ag nanowires with an increase in
      Raman hot spots and polarization-independent SERS signals across tens of
      micrometers length scale.

PMID- 22970779
TI  - The health and social consequences of adverse childhood experiences (ACE) across
      the lifespan: an introduction to prevention and intervention in the community.
AB  - This introduction to the themed issue overviews of the Adverse Childhood
      Experiences (ACE) Study and discusses prevention and intervention with ACE and
      their consequences in communities. A commentary by Dr. Robert Anda, an ACE Study
      Co-Principal Investigator, is incorporated within this introduction. Implications
      of articles within the issue are addressed, and next steps are explored.

PMID- 22970780
TI  - Translating the Adverse Childhood Experiences (ACE) Study into public policy:
      progress and possibility in Washington State.
AB  - On June 15, 2011, Washington became the first state in the United States to enact
      legislation aimed at preventing adverse childhood experiences (ACE), reducing
      their prevalence, and mitigating their effects. House Bill 1965 (HB 1965) was
      established on the understanding among legislators and Washington communities of
      the need for policies aimed at preventing child abuse, promoting healthy
      development of children, and building community capacity to improve public
      health. Empirical examples of integrating ACE-related research with public policy
      and programmatic design are chronicled. The legislators who developed HB 1965 lay
      out questions that, if answered, would further improve policymakers' ability to
      craft public policy and programs that prevent ACE, reduce their effects, and
      promote a healthier, safer future.

PMID- 22970781
TI  - Adverse childhood experiences (ACE) within a social disadvantage framework:
      distinguishing unique, cumulative, and moderated contributions to adult mental
      health.
AB  - The deleterious impact of adverse childhood experiences (ACE) may be confounded
      with frequently co-occurring social disadvantage. In this analysis we test the
      effects of ACE on adult mental health within a social disadvantage framework,
      using a population-based survey (n = 7,444; mean age = 55.2 years) from
      Washington State. We also examined the protective effects of socioemotional
      support, and the distinct and combined contribution of the measured ACE factors.
      Results demonstrated sustained impact of ACE on mental health many decades later,
      even net of social disadvantage and demographic contributors. Protective factors
      provided both direct and moderating influences, potentially masking the elevated
      effects of ACE for those with few resources. Toxicity examination of ACE items
      evinced differential effects of ACE experiences on mental health. These results
      demonstrate that interventions ameliorating the effects of ACE and bolstering
      protective resources such as socioemotional support may be effective toward
      augmenting mental health even late in life.

PMID- 22970782
TI  - Understanding adverse childhood experiences (ACE) and their relationship to adult
      stress among male survivors of childhood sexual abuse.
AB  - Men who were sexually abused during childhood represent a highly stigmatized,
      marginalized, and under-researched population at risk for a variety of problems
      across the lifespan. The purpose of the current study was to (a) describe
      characteristics of child sexual abuse (CSA) and adverse child experiences (ACE),
      and (b) examine the relationships among CSA characteristics, ACE, and stressors
      in adulthood. Using a cross-sectional design, the researcher collected data on
      487 adult men through an anonymous, online survey. Bivariate analyses revealed
      that five CSA characteristics--age at first abuse (r = -.164), number of abusers
      (r = .231), use of physical force, penetration, and physical injury--were related
      to the number of ACE. Three CSA characteristics (use of physical force,
      penetration, and physical injury) and the number of ACE (r = .162) were
      positively related to the number of stressors in adulthood. Preliminary
      recommendations for prevention, intervention, and future research are provided.

PMID- 22970783
TI  - Adolescent parents and their children: a multifaceted approach to prevention of
      adverse childhood experiences (ACE).
AB  - Childhood experiences can have long-term effects. Research shows that children
      who undergo adverse childhood experiences (ACE) often have negative health and
      mental health outcomes later in life. Children of adolescent parents with high
      ACE Scores are at greater risk of ACE. As such, an intergenerational approach to
      preventing ACE is proposed in this article, addressing the needs of both the
      adolescent parent and their children. A review of the literature indicates that a
      public health perspective can guide the development of a prevention model aimed
      at reducing the effects of ACE. The current article proposes a universal,
      multifaceted, and interdisciplinary prevention science model that has two
      targets: adolescent parents and their children. Schools and early childhood
      programs can be mobilized to offer community prevention strategies across realms
      to include the individual, community, provider, coalitions/networks,
      organizational practices, and policy/legislation.

PMID- 22970784
TI  - Educational-entertainment as an intervention with Black adolescents exposed to
      community violence.
AB  - Witnessing violence is one adverse childhood experience (ACE) associated with
      living in impoverished Black urban communities. Youth with higher violence
      avoidance self-efficacy and positive coping are more likely to avoid violence.
      This study evaluates educational entertainment (edutainment) as an intervention
      with Black adolescents exposed to community violence. Edutainment has shown
      success in increasing self-efficacy and positive coping skills in other domains.
      Self-administered scales were used to measure stress, anxiety, violence avoidance
      self-efficacy, and coping strategies. Data were collected pre- and nine days post
      interventions/no intervention from 20 subjects receiving the edutainment
      intervention, 19 subjects participating in a group discussion about violence, and
      21 subjects receiving no intervention (N = 60). Edutainment and no intervention
      were more effective than group discussion alone in increasing violence avoidance
      self-efficacy. Violence avoidance self-efficacy was found to have an intervening
      relationship between edutainment and the outcome of stress. This study indicates
      limited but positive effects for edutainment.

PMID- 22970785
TI  - Reducing adverse childhood experiences (ACE) by building community capacity: a
      summary of Washington Family Policy Council research findings.
AB  - Community capacity for organization and collaboration has been shown to be a
      powerful tool for improving the health and well-being of communities. Since 1994
      the Washington State Family Policy Council has supported the development of
      community capacity in 42 community public health and safety networks. Community
      networks bring local communities together to restructure natural supports and
      local resources to meet the needs of families and children, and increase cross
      system coordination and flexible funding streams to improve local services and
      policy. In this study, researchers sought to demonstrate the strong impact of the
      community networks' capacity to interrupt health and social problems. Findings
      suggest that community networks reduce health and safety problems for the entire
      community population. Further, community networks with high community capacity
      reduced adverse childhood experiences (ACE) in young adults ages 18-34.

PMID- 22970786
TI  - Mobilizing resilience and recovery in response to adverse childhood experiences
      (ACE): a Restorative Integral Support (RIS) case study.
AB  - The Restorative Integral Support (RIS) model is a comprehensive, whole person
      approach to addressing adversity and trauma. The Adverse Childhood Experiences
      (ACE) Study conducted by the Centers for Disease Control (CDC) and Kaiser
      Permanente reveals a relationship between childhood trauma and adult health and
      social problems. The current empirical case study presents the Committee on the
      Shelterless (COTS), in Petaluma, CA, as an example of one social service agency
      employing RIS to break cycles of homelessness. By applying RIS, research-based
      programming is offered within a culture of recovery that mobilizes resilience
      through social affiliations. The authors recommend RIS model implementation and
      research in programs serving populations with ACE backgrounds.

PMID- 22970788
TI  - Verticillium dahliae Sge1 differentially regulates expression of candidate
      effector genes.
AB  - The ascomycete fungus Verticillium dahliae causes vascular wilt diseases in
      hundreds of dicotyledonous plant species. However, thus far, only few V. dahliae
      effectors have been identified, and regulators of pathogenicity remain unknown.
      In this study, we investigated the role of the V. dahliae homolog of Sge1, a
      transcriptional regulator that was previously implicated in pathogenicity and
      effector gene expression in Fusarium oxysporum. We show that V. dahliae Sge1
      (VdSge1) is required for radial growth and production of asexual conidiospores,
      because VdSge1 deletion strains display reduced radial growth and reduced conidia
      production. Furthermore, we show that VdSge1 deletion strains have lost
      pathogenicity on tomato. Remarkably, VdSge1 is not required for induction of
      Ave1, the recently identified V. dahliae effector that activates resistance
      mediated by the Ve1 immune receptor in tomato. Further assessment of the role of
      VdSge1 in the induction of the nine most highly in-planta-induced genes that
      encode putative effectors revealed differential activity. Although the expression
      of one putative effector gene in addition to Ave1 was not affected by VdSge1
      deletion, VdSge1 appeared to be required for the expression of six putative
      effector genes, whereas two of the putative effectors genes were found to be
      negatively regulated by VdSge1. In conclusion, our data suggest that VdSge1
      differentially regulates V. dahliae effector gene expression.

PMID- 22970789
TI  - Intermittent lower-limb occlusion enhances recovery after strenuous exercise.
AB  - Repeated cycles of vascular occlusion followed by reperfusion initiate a
      protective mechanism that acts to mitigate future cell injury. Such ischemic
      episodes are known to improve vasodilation, oxygen utilization, muscle function,
      and have been demonstrated to enhance exercise performance. Thus, the use of
      occlusion cuffs represents a novel intervention that may improve subsequent
      exercise performance. Fourteen participants performed an exercise protocol that
      involved lower-body strength and power tests followed by repeated sprints.
      Occlusion cuffs were then applied unilaterally (2 * 3-min per leg) with a
      pressure of either 220 (intervention) or 15 mm Hg (control). Participants
      immediately repeated the exercise protocol, and then again 24 h later. The
      intervention elicited delayed beneficial effects (24 h post-intervention) in the
      countermovement jump test with concentric (effect size (ES) = 0.36) and eccentric
      (ES = 0.26) velocity recovering more rapidly compared with the control. There
      were also small beneficial effects on 10- and 40-m sprint times. In the squat
      jump test there were delayed beneficial effects of occlusion on eccentric power
      (ES = 1.38), acceleration (ES = 1.24), and an immediate positive effect on jump
      height (ES = 0.61). Thus, specific beneficial effects on recovery of power
      production and sprint performance were observed both immediately and 24 h after
      intermittent unilateral occlusion was applied to each leg.

PMID- 22970790
TI  - Energy expenditure during the LANY Footrace 2011 - a case study.
AB  - We reported results obtained in estimating the energy expenditure (EE) of an
      active adult subject participating in LANY Footrace 2011 (5129 km, 70 consecutive
      days). At each stage EE was calculated from literature metabolic cost equations
      and GPS-measured speeds-inclines. The subject's average speed was 7.41 +/- 0.51
      km.h(-1). Race expenditure amounted to 87% of EE (31.3 MJ.day(-1)) (47.8%-37.1%
      of measured maximal oxygen uptake). These results provide data about EE for
      future stage-type ultra-endurance competitors.

PMID- 22970791
TI  - ortho-Amidoalkylation of phenols via tandem one-pot approach involving oxazine
      intermediate.
AB  - A new and efficient method for ortho-amidoalkylation of phenols via Mannich-type
      condensation with formaldehyde and lactams using recyclable solid acid catalyst
      is described. This is the first report for ortho-amidoalkylation of phenols by
      lactams via Mannich-type condensation. LC-ESI-MS/MS based mechanistic study
      revealed that reaction proceeds through o-quinone methide (o-QM) and an oxazine
      intermediate via tandem Knoevenagel condensation, formal [4 + 2]-Diels-Alder
      cycloaddition and acid catalyzed oxazine ring-opening.

PMID- 22970792
TI  - Biological evaluation of the bone healing process after application of two
      potentially osteogenic proteins: an animal experimental model.
AB  - OBJECTIVE: The aim of this work was to analyse qualitatively and quantitatively
      the newly formed bone after insertion of rhBMP-2 and protein extracted from Hevea
      brasiliensis (P-1), associated or not with a carrier in critical bone defects
      created in Wistar rat calvarial bone, using histological and histomorphometrical
      analyses. MATERIALS AND METHODS: Eighty-four male Wistar rats were used, divided
      into two groups, according to the period of time until the sacrifice (2 and 6
      weeks). Each one of these groups was subdivided into six groups with seven
      animals each, according to the treatments: (1) 5 MUg of pure rhBMP-2, (2) 5 MUg
      of rhBMP-2/monoolein gel, (3) pure monoolein gel, (4) 5 MUg of pure P-1, (5) 5
      MUg of P-1/monoolein gel and (6) critical bone defect controls. The animals were
      euthanised and the calvarial bone tissue removed for histological and
      histomorphometrical analyses. RESULT AND CONCLUSION: The results showed an
      improvement in the bone healing process using the rhBMP-2 protein, associated or
      not with a material carrier in relation to the other groups, and this process
      demonstrated to be time dependent.

PMID- 22970793
TI  - Enrichment of previously uncultured bacteria from natural complex communities by
      adhesion to solid surfaces.
AB  - The adhesion to inert solid surfaces was explored as a novel approach for the
      enrichment of previously uncultured bacteria from natural microbial communities.
      Enrichments on solid steel, glass and synthetic polymeric surfaces were
      established using samples from five freshwater lakes, a marine microbial mat and
      an alpine soil, and were subsequently analysed by molecular fingerprinting and
      sequencing of their 16S rRNA gene fragments. The majority of the enriched
      phylotypes grouped with the Alphaproteobacteria, Betaproteobacteria or
      Bacteroidetes and in several cases were related to typical biofilm-forming
      species and genera. Most enrichments were most closely related to previously
      uncultured phylotypes and none had previously been cultivated from the original
      environments even when applying improved high throughput liquid cultivation
      techniques. Of the 13 phylotypes enriched from freshwater samples, seven were
      previously unknown, three matched so-far uncultured environmental clones, and
      three were identical to previously cultivated bacteria. Of the 17 phylotypes
      recovered from soil, 12 were previously unknown with five of these phylotypes
      representing novel genera, whereas five phylotypes were identical to previously
      cultured soil bacteria. The feasibility of the biofilm-enrichment approach was
      exemplified by the successful isolation of a not-yet cultured Betaproteobacterium
      that constituted a discernible component of the alpine soil microbial community
      in situ and exhibited only 93% similarity to its closest cultured relative. Based
      on these results, cultivation on solid surfaces represents a promising approach
      to recover isolates that have so far escaped cultivation as suspended cultures in
      liquid media.

PMID- 22970794
TI  - Simulation evaluation of statistical properties of methods for indirect and mixed
      treatment comparisons.
AB  - BACKGROUND: Indirect treatment comparison (ITC) and mixed treatment comparisons
      (MTC) have been increasingly used in network meta-analyses. This simulation study
      comprehensively investigated statistical properties and performances of commonly
      used ITC and MTC methods, including simple ITC (the Bucher method), frequentist
      and Bayesian MTC methods. METHODS: A simple network of three sets of two-arm
      trials with a closed loop was simulated. Different simulation scenarios were
      based on different number of trials, assumed treatment effects, extent of
      heterogeneity, bias and inconsistency. The performance of the ITC and MTC methods
      was measured by the type I error, statistical power, observed bias and mean
      squared error (MSE). RESULTS: When there are no biases in primary studies, all
      ITC and MTC methods investigated are on average unbiased. Depending on the extent
      and direction of biases in different sets of studies, ITC and MTC methods may be
      more or less biased than direct treatment comparisons (DTC). Of the methods
      investigated, the simple ITC method has the largest mean squared error (MSE). The
      DTC is superior to the ITC in terms of statistical power and MSE. Under the
      simulated circumstances in which there are no systematic biases and
      inconsistencies, the performances of MTC methods are generally better than the
      performance of the corresponding DTC methods. For inconsistency detection in
      network meta-analysis, the methods evaluated are on average unbiased. The
      statistical power of commonly used methods for detecting inconsistency is very
      low. CONCLUSIONS: The available methods for indirect and mixed treatment
      comparisons have different advantages and limitations, depending on whether data
      analysed satisfies underlying assumptions. To choose the most valid statistical
      methods for research synthesis, an appropriate assessment of primary studies
      included in evidence network is required.

PMID- 22970796
TI  - Generating CK19-positive cells with hair-like structures from Wharton's jelly
      mesenchymal stromal cells.
AB  - Wharton's jelly mesenchymal stromal cells (WJMSCs) are considered mesenchymal,
      multipotent, and capable of differentiating into cells of mesodermal origin.
      Ectodermal differentiation from mesenchymal cells has been recently reported.
      Herein, we show for the first time that we can generate cytokeratin 19-positive
      cells and hair-like structures from WJMSCs in vitro using 2 separate
      methodologies that utilize osteogenic media to induce WJMSCs to undergo
      osteogenic differentiation. In one method, WJMSCs were seeded on a matrix
      isolated from Wharton's jelly following decellularization. In the other method,
      WJMSCs were cultured to form spheroids. Our findings demonstrate that WJMSCs may
      have the capacity for ectodermal differentiation.

PMID- 22970795
TI  - Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation.
AB  - The toxicity of amyloid-forming peptides has been hypothesized to reside in the
      ability of protein oligomers to interact with and disrupt the cell membrane. Much
      of the evidence for this hypothesis comes from in vitro experiments using model
      membranes. However, the accuracy of this approach depends on the ability of the
      model membrane to accurately mimic the cell membrane. The effect of membrane
      composition has been overlooked in many studies of amyloid toxicity in model
      systems. By combining measurements of membrane binding, membrane
      permeabilization, and fiber formation, we show that lipids with the
      phosphatidylethanolamine (PE) headgroup strongly modulate the membrane disruption
      induced by IAPP (islet amyloid polypeptide protein), an amyloidogenic protein
      involved in type II diabetes. Our results suggest that PE lipids hamper the
      interaction of prefibrillar IAPP with membranes but enhance the membrane
      disruption correlated with the growth of fibers on the membrane surface via a
      detergent-like mechanism. These findings provide insights into the mechanism of
      membrane disruption induced by IAPP, suggesting a possible role of PE and other
      amyloids involved in other pathologies.

PMID- 22970798
TI  - Standardization of vascular assessment of erectile dysfunction: standard
      operating procedures for duplex ultrasound.
AB  - INTRODUCTION: In-office evaluation of erectile dysfunction by color duplex
      Doppler ultrasound (CDDU) may benefit the decision-making process in regard to
      choosing the most appropriate therapy. Unfortunately, there is no uniform
      standardization in performing CDDU resulting in high variability in data
      expression and interpretation when comparing results among various centers,
      especially when conducting multicenter trials. Establishing standard operating
      procedures (SOPs) is a major step that will help minimize such variability. AIM:
      This SOP describes CDDU procedure with focus on establishing uniformity and
      normative parameters. MAIN OUTCOME MEASURE: Measure intra-arterial diameter, peak
      systolic velocity, end-diastolic velocity, and resistive index for each
      cavernosal artery. METHODS: After initial discussion with the patient about his
      history and International Index of Erectile Function evaluation describe
      procedural steps to the patient. Perform the CDDU in a relaxed state, scanning
      the entire penis (in B-mode image) using a 7.5- to 12-MHz linear array ultrasound
      probe. An intracorporal injection of a single or combination of vasoactive agents
      (e.g., prostaglandin E1, phentolamine, and papaverine) is then administered and
      CDDU performed at various time points, preferably with audiovisual sexual
      stimulation (AVSS). RESULTS: Monitor penile erection response (tumescence and
      rigidity) near peak blood flow. Self-stimulation or AVSS leaving the patient
      alone in room or redosing may be considered to decrease any anxiety and help
      achieve a maximum rigid erection. CONCLUSION: Considering the complexity and
      heterogeneity of CDDU evaluation, this communication will help in standardization
      and establish uniformity in such data interpretation. When indicated, invasive
      diagnostic testing involving (i) penile angiography and (ii)
      cavernosography/cavernosometry to establish veno-occlusive dysfunction may be
      recommended to facilitate further treatment options.

PMID- 22970797
TI  - Social and economic costs and health-related quality of life in stroke survivors
      in the Canary Islands, Spain.
AB  - BACKGROUND: Cost-of-illness analysis is the main method of providing an overall
      vision of the economic impact of a disease. Such studies have been used to set
      priorities for healthcare policies and inform resource allocation. The aim of
      this study was to determine the economic burden and health-related quality of
      life (HRQOL) in the first, second and third years after surviving a stroke in the
      Canary Islands, Spain. METHODS: Cross-sectional, retrospective study of 448
      patients with stroke based on ICD 9 discharge codes, who received outpatient care
      at five hospitals. The study was approved by the Research Ethics Committee of
      Nuestra Senora de la Candelaria University Hospital. Data on demographic
      characteristics, health resource utilization, informal care, labor productivity
      losses and HRQOL were collected from the hospital admissions databases and
      questionnaires completed by stroke patients or their caregivers. Labor
      productivity losses were calculated from physical units and converted into
      monetary units with a human capital-based method. HRQOL was measured with the
      EuroQol EQ-5D questionnaire. Healthcare costs, productivity losses and informal
      care costs were analyzed with log-normal, probit and ordered probit multivariate
      models. RESULTS: The average cost for each stroke survivor was ?17 618 in the
      first, ?14 453 in the second and ?12 924 in the third year after the stroke; the
      reference year for unit prices was 2004. The largest expenditures in the first
      year were informal care and hospitalizations; in the second and third years the
      main costs were for informal care, productivity losses and medication. Mean EQ-5D
      index scores for stroke survivors were 0.50 for the first, 0.47 for the second
      and 0.46 for the third year, and mean EQ-5D visual analog scale scores were 56,
      52 and 55, respectively. CONCLUSIONS: The main strengths of this study lie in our
      bottom-up-approach to costing, and in the evaluation of stroke survivors from a
      broad perspective (societal costs) in the first, second and third years after
      surviving the stroke. This type of analysis is rare in the Spanish context. We
      conclude that stroke incurs considerable societal costs among survivors to three
      years and there is substantial deterioration in HRQOL.

PMID- 22970799
TI  - False positive spinal cord uptake on fluorodeoxyglucose positron-emission
      tomography following treatment of lymphoma.

PMID- 22970800
TI  - Pattern of bleeding and response to therapy in Glanzmann thrombasthenia.

PMID- 22970801
TI  - Elucidating the formation pathway of the off-flavor compound 6-propylbenzofuran-7
      ol.
AB  - In a previous work, we identified 6-propylbenzofuran-7-ol as an off-flavor
      compound formed from ascorbic acid and (E)-hex-2-enal in a test apple beverage.
      In this study, we elucidate the pathway by which 6-propylbenzofuran-7-ol formed.
      Isotope labeling studies revealed that the propyl group of 6-propylbenzofuran-7
      ol derives from (E)-hex-2-enal and that 6-propylbenzofuran-7-ol contains carbons
      2-6 of ascorbic acid. Two compounds, namely, 2,3-dihydro-6-propylbenzofuran-3,7
      diol and 3-(2-furoyl)hexanal, were identified as byproducts of a model reaction
      of ascorbic acid and (E)-hex-2-enal. Each of these compounds was dissolved in an
      aqueous solution of citric acid and stored at 60  degrees C for 1 week. After
      storage, 6-propylbenzofuran-7-ol was detected from a solution of 2,3-dihydro-6
      propylbenzofuran-3,7-diol, but not from 3-(2-furoyl)hexanal. 6-Propylbenzofuran-7
      ol was formed by isolating tricyclic hemiacetal lactone derived from the Michael
      addition of ascorbic acid to (E)-hex-2-enal, mixing the tricyclic hemiacetal
      lactone with the aqueous solution of citric acid, and applying heat. This
      confirmed that 6-propylbenzofuran-7-ol was formed via the Michael adduct. 

PMID- 22970802
TI  - Mycoredoxin-1 is one of the missing links in the oxidative stress defence
      mechanism of Mycobacteria.
AB  - To survive hostile conditions, the bacterial pathogen Mycobacterium tuberculosis
      produces millimolar concentrations of mycothiol as a redox buffer against
      oxidative stress. The reductases that couple the reducing power of mycothiol to
      redox active proteins in the cell are not known. We report a novel mycothiol
      dependent reductase (mycoredoxin-1) with a CGYC catalytic motif. With mycoredoxin
      1 and mycothiol deletion strains of Mycobacterium smegmatis, we show that
      mycoredoxin-1 and mycothiol are involved in the protection against oxidative
      stress. Mycoredoxin-1 acts as an oxidoreductase exclusively linked to the
      mycothiol electron transfer pathway and it can reduce S-mycothiolated mixed
      disulphides. Moreover, we solved the solution structures of oxidized and reduced
      mycoredoxin-1, revealing a thioredoxin fold with a putative mycothiol-binding
      site. With HSQC snapshots during electron transport, we visualize the reduction
      of oxidized mycoredoxin-1 as a function of time and find that mycoredoxin-1 gets
      S-mycothiolated on its N-terminal nucleophilic cysteine. Mycoredoxin-1 has a
      redox potential of -218 mV and hydrogen bonding with neighbouring residues lowers
      the pKa of its N-terminal nucleophilic cysteine. Determination of the oxidized
      and reduced structures of mycoredoxin-1, better understanding of mycothiol
      dependent reactions in general, will likely give new insights in how M.
      tuberculosis survives oxidative stress in human macrophages. 

PMID- 22970803
TI  - Geographic analysis of the feasibility of collocating algal biomass production
      with wastewater treatment plants.
AB  - Resource demand analyses indicate that algal biodiesel production would require
      unsustainable amounts of freshwater and fertilizer supplies. Alternatively,
      municipal wastewater effluent can be used, but this restricts production of algae
      to areas near wastewater treatment plants (WWTPs), and to date, there has been no
      geospatial analysis of the feasibility of collocating large algal ponds with
      WWTPs. The goals of this analysis were to determine the available areas by land
      cover type within radial extents (REs) up to 1.5 miles from WWTPs; to determine
      the limiting factor for algal production using wastewater; and to investigate the
      potential algal biomass production at urban, near-urban, and rural WWTPs in
      Kansas. Over 50% and 87% of the land around urban and rural WWTPs, respectively,
      was found to be potentially available for algal production. The analysis
      highlights a trade-off between urban WWTPs, which are generally land-limited but
      have excess wastewater effluent, and rural WWTPs, which are generally water
      limited but have 96% of the total available land. Overall, commercial-scale algae
      production collocated with WWTPs is feasible; 29% of the Kansas liquid fuel
      demand could be met with implementation of ponds within 1 mile of all WWTPs and
      supplementation of water and nutrients when these are limited.

PMID- 22970804
TI  - Spectral optical coherence tomography findings in patients with ocular
      toxoplasmosis and active satellite lesions (MINAS Report 1).
AB  - PURPOSE: To characterize the active retinochoroiditis lesion observed in patients
      with the classic clinical presentation of ocular toxoplasmosis (OT) utilizing
      spectral optical coherence tomography (SOCT). METHODS: Twenty-four patients with
      OT and satellite lesions underwent standardized ophthalmologic examination and
      multimodal fundus imaging. The SOCT findings observed at presentation were
      described. RESULTS: The mean age of the fourteen (58.3%) women and ten (41.7%)
      men was 27.6 years. The mean LogMAR ETDRS best-corrected visual acuity was 0.58
      (Snellen equivalent, 20/80(+1) ). On SOCT evaluation, the posterior hyaloid was
      diffusely thickened in 23 (95.8%) of 24 eyes, increased hyper-reflective signals
      in the vitreous were observed in 18 (75.0%), and vitreal spherical hyper
      reflective depositions were observed in 12 (50.0%) eyes. In all patients, at the
      active OT lesion site, the inner retinal layers were abnormally hyper-reflective
      with full-thickness disorganization of the retinal reflective layers (smudge
      effect); associated choriocapillaris/choroidal optical shadowing was observed in
      22 (91.7%) eyes. The retina was thickened in 22 (91.7%) eyes, the retinal pigment
      epithelium-Bruch membrane reflective complex was focally increased or contained
      focal splits in 16 (66.7%) eyes and the choroid appeared thickened in 17 (70.8%)
      eyes. Disorganization of the outer retinal highly reflective layers adjacent to
      the active OT lesion was observed in all eyes. CONCLUSION: Full-thickness
      disorganization of the retinal reflective layers, generally associated with some
      degree of posterior optical shadowing, was observed in the active OT lesion in
      all patients. The posterior hyaloid was often thickened and, adjacent to the OT
      lesion, the outer retina was consistently altered.

PMID- 22970805
TI  - Graphene oxide-based hydrogels to make metal nanoparticle-containing reduced
      graphene oxide-based functional hybrid hydrogels.
AB  - In this study, stable supramolecular hydrogels have been obtained from the
      assembly of graphene oxide (GO) in presence of polyamines including
      tris(aminoethyl)amine, spermine, and spermidine [biologically active molecule].
      One of these hydrogels has been well characterized by various techniques
      including field-emission scanning electron microscopy (FE-SEM), transmission
      electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD)
      study, and Raman spectroscopy. TEM and AFM studies of one of these hydrogels have
      revealed the presence of a network structure of cross-linked nanosheets. This
      suggests the supramolecular assembly of GO in the presence of polyamines using
      the acid-base type electrostatic interaction. In presence of a mild reducing
      agent (vitamin C), one of these GO hydrogels has been transformed into a reduced
      graphene oxide (RGO)-based hydrogel by a simple in situ reduction of GO sheets
      within the hydrogel matrix. Moreover, noble metal nanoparticle containing RGO
      based hybrid hydrogels have been obtained using in situ and simultaneous co
      reduction of GO and noble metal precursors within the GO gel matrix. The elegance
      of this method is in situ, "green chemical" and simultaneous reduction of GO and
      metal salts within the hydrogel matrix to form RGO-based hybrid gel and
      concomitant stabilization of metal nanoparticles (MNPs) within the gel system.
      The nascently formed MNPs are homogeneously and uniformly distributed on the
      surface of the RGO nanosheets within the hybrid gel. Interestingly, this MNP
      containing RGO-based hybrid hydrogel matrix acts as a potential catalyst for the
      reduction of aromatic nitro to amino group. The catalyst (hybrid gel matrix) can
      be separated easily after the reaction and reused several times.

PMID- 22970808
TI  - Respiratory distress in a one-month-old child suffering brachial plexus palsy.
AB  - This paper describes a one-month-old girl presenting with respiratory and growth
      failure due to diaphragmatic paralysis associated with left brachial plexus palsy
      after forceps delivery. Despite continuous positive pressure ventilation and
      nasogastric feeding, the situation did not improve and a laparoscopic
      diaphragmatic plication had to be performed. When dealing with a child born with
      brachial plexus palsy, one must think of this possible association and if
      necessary proceed to the complementary radiological examinations. The treatment
      must avoid complications like feeding difficulties and failure to thrive,
      respiratory infections or atelectasis. It includes intensive support and a good
      evaluation of the prognosis of the lesion to decide the best moment for a
      surgical therapy.

PMID- 22970810
TI  - Fields of dreams. Abstracts of the Canadian Society for Exercise Physiology
      Annual General Meeting. October 10-13, 2012. Delta Regina, Regina, Saskatchewan,
      Canada.

PMID- 22970807
TI  - Human T-cell proliferation in response to thrombin-activated GTKO pig endothelial
      cells.
AB  - BACKGROUND: Thrombin formation is a key feature in the activation of coagulation
      in pig xenograft recipients. As thrombin is known to activate endothelial and
      immune cells, we explored whether thrombin activation of pig endothelial cells
      (EC) was associated with an increased human T-cell response. METHODS: alpha1,3
      galactosyltransferase gene-knockout (GTKO) pig aortic EC (pAEC) were activated by
      porcine interferon-gamma (pIFNgamma), human (h)IFN-gamma, or thrombin. Swine
      leukocyte antigen (SLA) class I and class II expression were measured. Human
      peripheral blood mononuclear cells (PBMC) and CD4+ T-cell proliferation in
      response to activated pAEC, the effect of thrombin on pig CD80/CD86 mRNA, and the
      effect of thrombin inhibition by hirudin were evaluated. RESULTS: After pAEC
      activation, SLA I expression did not change, and only pIFNgamma upregulated SLA
      II expression. PBMC proliferation to pIFNgamma- and thrombin-activated pAEC was
      significantly higher (P < 0.001 and P < 0.01) than to non-activated pAEC. CD4+ T
      cell proliferation to pIFNgamma- and thrombin-activated pAEC was significantly
      higher (P < 0.001 and P < 0.01) than to non-activated pAEC. Thrombin inhibition
      by hirudin reduced thrombin-induced upregulation of pAEC CD86 mRNA, and
      significantly reduced human PBMC proliferation to pAEC in comparison with
      thrombin alone (P < 0.05). CONCLUSIONS: Thrombin upregulates CD86 mRNA on pAEC,
      which is associated with increased human T-cell proliferation against pAEC.
      Hirudin reduces CD86 mRNA in thrombin-activated pAEC and is associated with
      downregulation of the human T-cell proliferative response. The transplantation of
      organs from GTKO pigs transgenic for human thrombomodulin, and/or endothelial
      protein C receptor, in addition to therapeutic regulation of thrombin activation
      may reduce the cellular response to a pig xenograft and thus reduce the need for
      intensive immunosuppressive therapy.

PMID- 22970809
TI  - The yeast vacuolar ABC transporter Ybt1p regulates membrane fusion through Ca2+
      transport modulation.
AB  - Ybt1p is a class C ABC transporter (ATP-binding cassette transporter) that is
      localized to the vacuole of Saccharomyces cerevisiae. Although Ybt1p was
      originally identified as a bile acid transporter, it has also been found to
      function in other capacities, including the translocation of phosphatidylcholine
      to the vacuole lumen, and the regulation of Ca2+ homoeostasis. In the present
      study we found that deletion of YBT1 enhanced in vitro homotypic vacuole fusion
      by up to 50% relative to wild-type vacuoles. The increased vacuole fusion was not
      due to aberrant protein sorting of SNAREs (soluble N-ethylmaleimide-sensitive
      factor-attachment protein receptors) or recruitment of factors from the cytosol
      such as Ypt7p and the HOPS (homotypic fusion and vacuole protein sorting)
      tethering complex. In addition, ybt1Delta vacuoles displayed no observable
      differences in the formation of SNARE complexes, interactions between SNAREs and
      HOPS, or formation of vertex microdomains. However, the absence of Ybt1p caused
      significant changes in Ca2+ transport during fusion. One difference was the
      prolonged Ca2+ influx exhibited by ybt1Delta vacuoles at the start of the fusion
      reaction. We also observed a striking delay in SNARE-dependent Ca2+ efflux. As
      vacuole fusion can be inhibited by high Ca2+ concentrations, we suggest that the
      delayed efflux in ybt1Delta vacuoles leads to the enhanced SNARE function.

PMID- 22970811
TI  - Chances and limits of an improved method to assess water resistance of cosmetic
      sunscreen products in vitro on polymethylmethacrylate plates.
AB  - While sun protection factor (SPF) and UVA protection are the most important
      determinants of a cosmetic sunscreen product, water resistance is the third
      important feature. The Colipa in vivo method is the internationally accepted
      standard method to assess water resistance. It is time-consuming and expensive. A
      screening method to quickly predict water resistance properties on low cost
      therefore is a specific request of product developers. Several in vitro screening
      methods are published but the predictive power of all these methods is limited.
      In this paper, we describe an adaptation of the in vitro UVA protection method of
      Colipa for a water resistance screening. Although the method is quick and most
      parts are standardized and approved by Colipa, the results were not in advantage
      of other published screening methods. Taking into account, the scatter of the
      results, seven of 16 sunscreen products that were developed as water resistant
      formulations could be unambiguously estimated to be water resistant by the in
      vivo water resistance screening method on five subjects while nine failed. In 10
      of these 16 results, the in vitro SPF-based method was in accordance with in vivo
      findings, whereas in six cases, the method was not predicting correctly. Based on
      these results, the authors recommend to use the in vitro screening methods to pre
      select from candidates which cannot all be tested in vivo. The pre-selected
      products can be screened in the Colipa in vivo water resistance method with a
      reduced number of volunteers (usually 5) to predict water resistance. In case,
      the water resistance estimated in such an in vivo screening is found at about 65%
      or higher the study can be deemed successful and completed with further subjects
      to fulfil the Colipa requirements.

PMID- 22970812
TI  - Classification of positive blood cultures: computer algorithms versus physicians'
      assessment--development of tools for surveillance of bloodstream infection
      prognosis using population-based laboratory databases.
AB  - BACKGROUND: Information from blood cultures is utilized for infection control,
      public health surveillance, and clinical outcome research. This information can
      be enriched by physicians' assessments of positive blood cultures, which are,
      however, often available from selected patient groups or pathogens only. The aim
      of this work was to determine whether patients with positive blood cultures can
      be classified effectively for outcome research in epidemiological studies by the
      use of administrative data and computer algorithms, taking physicians'
      assessments as reference. METHODS: Physicians' assessments of positive blood
      cultures were routinely recorded at two Danish hospitals from 2006 through 2008.
      The physicians' assessments classified positive blood cultures as: a)
      contamination or bloodstream infection; b) bloodstream infection as mono- or
      polymicrobial; c) bloodstream infection as community- or hospital-onset; d)
      community-onset bloodstream infection as healthcare-associated or not. We applied
      the computer algorithms to data from laboratory databases and the Danish National
      Patient Registry to classify the same groups and compared these with the
      physicians' assessments as reference episodes. For each classification, we
      tabulated episodes derived by the physicians' assessment and the computer
      algorithm and compared 30-day mortality between concordant and discrepant groups
      with adjustment for age, gender, and comorbidity. RESULTS: Physicians derived
      9,482 reference episodes from 21,705 positive blood cultures. The agreement
      between computer algorithms and physicians' assessments was high for
      contamination vs. bloodstream infection (8,966/9,482 reference episodes [96.6%],
      Kappa = 0.83) and mono- vs. polymicrobial bloodstream infection (6,932/7,288
      reference episodes [95.2%], Kappa = 0.76), but lower for community- vs. hospital
      onset bloodstream infection (6,056/7,288 reference episodes [83.1%], Kappa =
      0.57) and healthcare-association (3,032/4,740 reference episodes [64.0%], Kappa =
      0.15). The 30-day mortality in the discrepant groups differed from the concordant
      groups as regards community- vs. hospital-onset, whereas there were no material
      differences within the other comparison groups. CONCLUSIONS: Using data from
      health administrative registries, we found high agreement between the computer
      algorithms and the physicians' assessments as regards contamination vs.
      bloodstream infection and monomicrobial vs. polymicrobial bloodstream infection,
      whereas there was only moderate agreement between the computer algorithms and the
      physicians' assessments concerning the place of onset. These results provide new
      information on the utility of computer algorithms derived from health
      administrative registries.

PMID- 22970814
TI  - An erythematous papular lesion on the neck of a young boy. Elastosis perforans
      serpiginosa.

PMID- 22970813
TI  - Role of Rhizobium endoglucanase CelC2 in cellulose biosynthesis and biofilm
      formation on plant roots and abiotic surfaces.
AB  - BACKGROUND: The synthesis of cellulose is among the most important but poorly
      understood biochemical processes, especially in bacteria, due to its complexity
      and high degree of regulation. In this study, we analyzed both the production of
      cellulose by all known members of the Rhizobiaceae and the diversity of Rhizobium
      celABC operon predicted to be involved in cellulose biosynthesis. We also
      investigated the involvement in cellulose production and biofilm formation of
      celC gene encoding an endoglucanase (CelC2) that is required for canonical
      symbiotic root hair infection by Rhizobium leguminosarum bv. trifolii. RESULTS:
      ANU843 celC mutants lacking (ANU843DeltaC2) or overproducing cellulase
      (ANU843C2+) produced greatly increased or reduced amounts of external cellulose
      micro fibrils, respectively. Calcofluor-stained cellulose micro fibrils were
      considerably longer when formed by ANU843DeltaC2 bacteria rather than by the wild
      type strain, in correlation with a significant increase in their flocculation in
      batch culture. In contrast, neither calcofluor-stained extracellular micro
      fibrils nor flocculation was detectable in ANU843C2+ cells. To clarify the role
      of cellulose synthesis in Rhizobium cell aggregation and attachment, we analyzed
      the ability of these mutants to produce biofilms on different surfaces.
      Alteration of wild-type CelC2 levels resulted in a reduced ability of bacteria to
      form biofilms both in abiotic surfaces and in planta. CONCLUSIONS: Our results
      support a key role of the CelC2 cellulase in cellulose biosynthesis by modulating
      the length of the cellulose fibrils that mediate firm adhesion among Rhizobium
      bacteria leading to biofilm formation. Rhizobium cellulose is an essential
      component of the biofilm polysaccharidic matrix architecture and either an excess
      or a defect of this "building material" seem to collapse the biofilm structure.
      These results position cellulose hydrolytic enzymes as excellent anti-biofilm
      candidates.

PMID- 22970815
TI  - Circular erythematous patch in a febrile infant. Cold panniculitis.

PMID- 22970816
TI  - Solitary nodule on the base of the nose in an adolescent girl. Cellular
      neurothekeoma.

PMID- 22970819
TI  - Adjusting membrane lipids under salt stress: the case of the moderate halophilic
      organism Halobacillus halophilus.
AB  - The lipid composition of Halobacillus halophilus was investigated by combined
      thin-layer chromatography and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry analyses of the total lipid extract. Main polar lipids
      were found to be sulfoquinovosyldiacylglycerol and phosphatidylglycerol, while
      cardiolipin was a minor lipid together with phosphatidic acid, alanyl
      phosphatidylglycerol and two not yet fully identified lipid components. In
      addition the analyses of residual lipids, associated with denatured proteins
      after the lipid extraction, revealed the presence of significant amounts of
      cardiolipin, indicating that it is a not readily extractable phospholipid. Post
      decay source mass spectrometry analyses allowed the determination of acyl chains
      of main lipid components. On increasing the culture medium salinity, an increase
      in the shorter chains and the presence of chain unsaturations were observed.
      These changes in the lipid core structures might compensate for the increase in
      packing and rigidity of phospholipid and sulfoglycolipid polar heads in high-salt
      medium, therefore contributing to the homeostasis of membrane fluidity and
      permeability in salt stress conditions.

PMID- 22970818
TI  - Methyljasmonate displays in vitro and in vivo activity against multiple myeloma
      cells.
AB  - Jasmonates, plant stress hormones, have been demonstrated to be effective in
      killing various types of cancer cells. We therefore tested if methyljasmonate
      (MJ) has activity against multiple myeloma (MM) in vitro and in vivo. MM cell
      lines and primary MM tumour cells responded to MJ in vitro at concentrations that
      did not significantly affect normal haematopoietic cells, without stroma-mediated
      resistance. Brief MJ exposures of MM cells caused release of Hexokinase 2 (HK2)
      from mitochondria, rapid ATP depletion, perturbation of major intracellular
      signalling pathways, and ensuing mainly apoptotic cell death. Sensitivity to MJ
      correlated with lower cellular glucose consumption and lactate production, as
      well as lower intracellular protein levels of HK2, phosphorylated Voltage
      dependent anion channel 2/3 (pVDAC2/3) and Aldo-keto reductase family 1 member C1
      (AKR1C1), which represent potential biomarkers of responsiveness to MJ treatment,
      especially as AKR1C1 transcript levels also correlate with clinical outcome in
      bortezomib- or dexamethasone-treated MM patients. Interestingly, MJ synergized
      with bortezomib in vitro and prolonged survival of immunocompromised mice
      harbouring diffuse lesions of MM.1S cells compared to vehicle-treated mice (P =
      0.0046). These studies indicate that jasmonates represent a new, promising
      strategy to treat MM.

PMID- 22970820
TI  - Comprehensive synthesis of photoreactive (3-trifluoromethyl)diazirinyl indole
      derivatives from 5- and 6- trifluoroacetylindoles for photoaffinity labeling.
AB  - 5- and 6-trifluoromethyldiazirinyl indoles were synthesized from corresponding
      bromoindole derivatives for the first time. They acted as mother skeletons for
      the comprehensive synthesis of various bioactive indole metabolites. These can be
      used in biological functional analysis as diazirine-based photoaffinity labels.

PMID- 22970821
TI  - Family structure, socioeconomic position and utilization of oral health services
      among Nigerian senior secondary school pupils.
AB  - OBJECTIVE: To test the relationship between socioeconomic position (SEP), family
      composition, number of siblings, and birth position in the family, and the
      utilization of oral health services by senior secondary school pupils in Ile-Ife,
      Nigeria. METHODS: A cross-sectional study design included senior secondary school
      pupils in the Central Local Government Area of Ile-Ife during 2007/2008. Sample
      size calculation was performed and 1,200 pupils were invited to participate. A
      multistage, stratified sampling technique was used. Data collection included a
      self-administered questionnaire. Data were analyzed using logistic regression.
      RESULTS: The response rate was 76 percent (n=1043). The mean age was 15.8
      (standard deviation=1.9) and 49 percent were males. Only 22.5 percent of pupils
      had ever visited a dentist in their lives. Results from multivariate analyses
      showed that pupils attending free schools, those paying 1 to 10,000 naira
      (equivalent to US$ 63.31) and 10,000 to 19,000 naira (equivalent to US$ 120.29)
      were respectively 1.93, 1.87, and 2.74 times less likely to have attended a
      dentist in the past than pupils in more expensive schools. Pupils living with
      single mothers or without a parent were unlikely to have visited the dentist.
      Number of siblings and birth position in the family were not associated with
      utilization of oral health services. CONCLUSIONS: Adolescents from families with
      a low SEP growing up without their parents may need extra incentives to visit
      dentist.

PMID- 22970822
TI  - Standard operating procedures for female genital sexual pain.
AB  - INTRODUCTION: Female genital sexual pain (GSP) is a common, distressing complaint
      in women of all ages that is underrecognized and undertreated. Definitions and
      terminology for female GSP are currently being debated. While some authors have
      suggested that GSP is not per se a sexual dysfunction, but rather a localized
      genial pain syndrome, others adhere to using clearly sexually related terms such
      as dyspareunia and vaginismus. AIM: The aims of this brief review are to present
      definitions of the different types of female GSP. Their etiology, incidence,
      prevalence, and comorbidity with somatic and psychological disorders are
      highlighted, and different somatic and psychological assessment and treatment
      modalities are discussed. METHODS: The Standard Operating Procedures (SOP)
      committee was composed of a chair and five additional experts. No corporate
      funding or remuneration was received. The authors agreed to survey relevant
      databases, journal articles and utilize their own clinical experience. Consensus
      was guided by systematic discussions by e-mail communications. MAIN
      OUTCOME/RESULTS: There is a clear lack of epidemiological data defining female
      GSP disorders and a lack of evidence supporting therapeutic interventions.
      However, this international expert group will recommend guidelines for management
      of female GSP. CONCLUSIONS: GSP disorders are complex. It is recommended that
      their evaluation and treatment are performed through comprehensive somato
      psychological multidisciplinary approach.

PMID- 22970823
TI  - Abstracts of the 11th Biennial Congress of the European Association of Oral
      Medicine. September 13-15, 2012. Athens, Greece.

PMID- 22970824
TI  - Conjugated polyelectrolyte dendrimers: aggregation, photophysics, and amplified
      quenching.
AB  - Conjugated polyelectrolyte dendrimers (CPDs) are monodisperse macromolecules that
      feature a fully pi-conjugated dendrimer core surrounded on the periphery by ionic
      solubilizing groups. CPDs are soluble in water and polar organic solvents, and
      they exhibit photophysics characteristic of the pi-conjugated chromophores
      comprising the dendrimer core. Here we describe the synthesis and photophysical
      characterization of series of three generations of CPDs based on a phenylene
      ethynylene repeat unit structure that is surrounded by an array of anionic sodium
      carboxylate groups. Molecular dynamics simulations indicate that the first
      generation CPD is flat while the second- and third-generation CPDs adopt oblate
      structures. Photophysical studies, including absorption, fluorescence
      spectroscopy, and lifetimes, show that the ester protected precursor dendrimers
      exhibit highly efficient blue fluorescence in THF solution emanating from the
      phenylene ethynylene chromophore that is in the dendrimer core. By contrast, the
      water-soluble CPDs have much lower fluorescence quantum yields and the absorption
      and fluorescence spectra exhibit features of strong chromophore-chromophore
      interactions. The results are interpreted as suggesting that the CPDs exist as
      dimer or multimer aggregates, even in very dilute solution. Fluorescence
      quenching of the anionic CPDs with the dication electron acceptor N,N'
      dimethylviologen (MV(2+)) is very efficient, with Stern-Volmer quenching
      constants (K(SV)) increasing with generation number. The third-generation CPD
      exhibits highly efficient amplified quenching, with K(SV) ~ 5 * 10(6) M(-1).

PMID- 22970825
TI  - Oat beta-glucan increased ATPases activity and energy charge in small intestine
      of rats.
AB  - Dietary oat or oat products may potentially help to fight against high risk of
      cardiovascular diseases and beta-glucan in oat was considered as a central
      player. The present study aimed to investigate the effects of dietary oat whole
      meal or beta-glucan on insulin sensitivity and energy metabolism of rats. Rats
      were fed with control diet, oat whole meal based diet, or control diet with
      supplemented beta-glucan for 4 weeks. Oat whole meal and beta-glucan increased
      insulin sensitivity index. Interestingly, supplementation of oat whole meal or
      beta-glucan induced increases in intestinal Na(+)K(+)-ATPase activity,
      Ca(2+)Mg(2+)-ATPase activity, and energy charge, particularly in the distal part
      of small intestine (ileum). Furthermore, amounts of  Bifidobacterium  and 
      Lactobacillus  in colon contents were elevated by oat whole meal or beta-glucan.
      These findings provide an insight into that beta-glucan increased insulin
      sensitivity and benefited intestinal health.

PMID- 22970826
TI  - Exploring psychosocial support online: a content analysis of messages in an
      adolescent and young adult cancer community.
AB  - The increased usage of online cancer support groups as a resource for health
      related information and social support has sparked numerous discussions about the
      role of online support in healthcare. However, little is known about the role of
      social-networking groups focused on supporting adolescents and young adults
      (AYAs) dealing with cancer. The current investigation report findings from a
      content analysis designed to explore how AYAs use an online support group to meet
      their psychosocial needs. Overall, members of the community focused on exchanging
      emotional and informational support, coping with difficult emotions through
      expression, describing experiences of being an AYA dealing with cancer through
      language (metaphors), enacting identity through evaluations of the new normal
      (life with and after cancer), and communicating membership as an AYA with cancer.
      This study highlights the unique needs of the AYA cancer community and offers a
      preliminary roadmap for practitioners, and network members, such as family and
      friends, to attempt to meet the needs of this unique community.

PMID- 22970827
TI  - Are they talking to me? Cognitive and affective effects of interactivity in
      politicians' twitter communication.
AB  - The present study investigated when and how the level of interactivity in
      politicians' Twitter communication affects the public's cognitive and affective
      reactions. In a Web-based experiment (n=264), participants viewed a high profile
      male politician's Twitter page, wherein he was either actively responding to his
      followers' questions (high interactivity) or mostly posting messages on his own
      (low interactivity). Exposure to the high-interactivity Twitter page induced a
      stronger sense of direct conversation with the candidate (social presence), but
      only among less affiliative individuals who usually avoid social interaction.
      Heightened social presence, in turn, led to more positive overall evaluations of
      the candidate and a stronger intention to vote for him. Although those in the
      high-interactivity condition generated more positive thoughts, they had fewer
      issue-related thoughts and exhibited poorer recognition of the issues mentioned
      by the candidate.

PMID- 22970828
TI  - A modular strategy for fully conjugated donor-acceptor block copolymers.
AB  - A novel strategy for the synthesis of fully conjugated donor-acceptor block
      copolymers, in a single reaction step employing Stille coupling polymerization of
      end-functional polythiophene and AA + BB monomers, is presented. The unique donor
      acceptor structure of these block copolymers provides a rich self-assembly
      behavior, with the first example of a fully conjugated donor-acceptor block
      copolymer having two separate crystalline domains being obtained.

PMID- 22970829
TI  - Biocompatible hydrogels by oxime Click chemistry.
AB  - Oxime Click chemistry was used to form hydrogels that support cell adhesion.
      Eight-armed aminooxy poly(ethylene glycol) (PEG) was mixed with glutaraldehyde to
      form oxime-linked hydrogels. The mechanical properties, gelation kinetics, and
      water swelling ratios were studied and found to be tunable. It was also shown
      that gels containing the integrin ligand arginine-glycine-aspartic acid (RGD)
      supported mesenchymal stem cell (MSC) incorporation. High cell viability and
      proliferation of the encapsulated cells demonstrated biocompatibility of the
      material.

PMID- 22970830
TI  - The basic chromospheres of skin that might not be differentiated visually:
      observations on aneurysmal fibrous histiocytomas and malignant melanomas.
AB  - AIM: Aneurysmal fibrous histiocytoma (AFH) is a variant of fibrous histiocytoma,
      which has a cleft-like cavernous blood-filled space in the tumor. It appears as a
      single reddish black tumor with variable levels of pain and size from its
      bleeding. And, it must be differentiated from other similar looking malignant
      conditions such as malignant melanoma. The visual mimicry of AFH to melanoma was
      raised by some careful dermatologists, but never be confirmed objectively by
      colorimetric analysis. MATERIALS, SUBJECTS, AND METHODS: In this study, we simply
      analyzed conventionally photographed digital images of thirty-seven cases of
      fibrous histiocytomas, including three AFH cases into colorimetrically useful
      color space, CIELAB, of which coordinates are L*, a*, and b* representing
      lightness, red to green, and yellow to blue axis, respectively. In addition, we
      also analyzed the clinical digital images of seven cases of malignant melanomas.
      Using statistical package, each coordinates of CIELAB were compared using
      Wilcoxon rank sum test between AFH and melanomas. The CIELAB coordinates of AFH
      and non-aneurysmal fibrous histiocytomas were compared statistically as well.
      RESULTS: Comparing with banal fibrous histiocytomas, the colors of AFH showed
      significantly smaller a* and b* coordinates (P = 0.008, 0.008, respectively),
      which implies more green and blue hue of AFH lesion. Rather, they were more like
      melanomas (P = 0.2839, 0.2040, respectively). As for L*, there were no
      significant differences for all comparisons. CONCLUSIONS: As a result, more
      objective analysis of the digital images using colorimetric color space confirmed
      the visual mimicry of AFH to melanoma.

PMID- 22970831
TI  - Fast and slow rates of naphthalene sorption to biochars produced at different
      temperatures.
AB  - This study investigated the sorption kinetics of a model solute (naphthalene)
      with a series of biochars prepared from a pine wood at 150-700  degrees C
      (referred as PW100-PW700) to probe the effect of the degree of carbonization of a
      biochar. The samples were characterized by the elemental compositions, thermal
      gravimetric analyses, Fourier transform IR spectroscopy, scanning electron
      microscopy, Brunauer-Emmett-Teller-N(2) surface areas (SA), and pore size
      distributions. Naphthalene exhibited a fast rate of sorption to PW150 owning a
      high oxygen content and a small SA, due supposedly to the solute partition into a
      swollen well-hydrated uncarbonized organic matter of PW150. The partial removal
      of polar-group contents in PW250/PW350, which increased the compactness of the
      partition medium, decreased the diffusion of the solute into the partition phase
      to result in a slow sorption rate. With PW500 and PW700 displaying low oxygen
      contents and high SA, the solute sorption rates were fast, attributed to the near
      exhaustion of a partition phase in the sample and to the fast solute adsorption
      on the carbonized biochar component. The results illustrate that the sorption
      rate of a solute with biochars is controlled largely by the solute's diffusivity
      in the biochar's partition phase, in which the medium compactness affects
      directly the solute diffusivity.

PMID- 22970832
TI  - Preparation of a responsive carbohydrate-coated biointerface based on
      graphene/azido-terminated tetrathiafulvalene nanohybrid material.
AB  - A one-step method for the reduction of graphene oxide (GO) to reduced graphene
      oxide (rGO) is reported  taking advantage of the electron-donor properties of an
      azido-terminated tetrathiafulvalene (TTF-N(3)). The resulting graphene/TTF-N(3)
      nanohybrid material is characterized by X-ray photoelectron spectroscopy (XPS),
      Fourier transform infrared spectroscopy (FT-IR) spectroscopy, and by electrical
      and electrochemical means. The accessibility of the azide function to
      chemoselective modification by any alkyne-terminated partner molecule via Cu(I)
      catalyzed "click" chemistry is demonstrated. In a proof of principle and
      motivated by the importance of glycan-modified materials, many alkynyl-terminated
      mannose units were grated onto graphene/TTF-N(3). The TTF-mannose units could be
      released efficiently from the graphene matrix by chemical oxidation of TTF
      mannose surface units to TTF(2+)-mannose, using Fe(ClO(4))(3) or the electron
      deficient tetracationic cyclophane cyclobis(paraquat-p-phenylene) (CBPQT(4+)).

PMID- 22970833
TI  - Assessing children's dental anxiety: a systematic review of current measures.
AB  - The reliable assessment of children's dental anxiety can have many benefits for
      the dental team, service providers and dental public health practitioners. This
      study aimed to identify and evaluate self-report measures, which are available to
      assess children's dental anxiety. Systematic searches of the literature between
      1998 and 2011 were conducted to identify relevant studies. The properties of each
      measure (reliability and validity) were assessed, and measures were evaluated
      against a theoretical framework of dental anxiety. Executing the search strategy
      generated 498 articles and of these 60 studies met all of the inclusion criteria.
      Seven 'trait' and two 'state' measures of dental anxiety had been employed to
      assess children's dental anxiety over the past decade. Reliability and validity
      estimates for the most widely used measures were good; however, many
      questionnaires had a limited focus in the aspects of anxiety they assessed. The
      paper summarizes the measures of children's dental anxiety which may be most
      useful for a number of different purposes and populations.

PMID- 22970834
TI  - Characterization of the velvet regulators in Aspergillus fumigatus.
AB  - Fungal development and secondary metabolism is intimately associated via
      activities of the fungi-specific velvet family proteins. Here we characterize the
      four velvet regulators in the opportunistic human pathogen Aspergillus fumigatus.
      The deletion of AfuvosA, AfuveA and AfuvelB causes hyperactive asexual
      development (conidiation) and precocious and elevated accumulation of AfubrlA
      during developmental progression. Moreover, the absence of AfuvosA, AfuveA or
      AfuvelB results in the abundant formation of conidiophores and highly increased
      AfubrlA mRNA accumulation in liquid submerged culture, suggesting that they act
      as repressors of conidiation. The deletion of AfuvosA or AfuvelB causes a
      reduction in conidial trehalose amount, long-term spore viability, conidial
      tolerance to oxidative and UV stresses, and accelerated and elevated conidial
      germination regardless of the presence or absence of an external carbon source,
      suggesting an interdependent role of them in many aspects of fungal biology.
      Genetic studies suggest that AfuAbaA activates AfuvosA and AfuvelB expression
      during the mid to late phase of conidiation. Finally, the AfuveA null mutation
      can be fully complemented by Aspergillus nidulans VeA, which can physically
      interact with AfuVelB and AfuLaeA in vivo. A model depicting the similar yet
      different roles of the velvet regulators governing conidiation and sporogenesis
      in A. fumigatus is presented.

PMID- 22970835
TI  - Need to consensus for novel findings by optical coherence tomography in patients
      with age-related macular degeneration.

PMID- 22970836
TI  - Missed congenital hypothyroidism in an identical twin.
AB  - Newborn screening for congenital hypothyroidism has been remarkably effective,
      although rare cases of false negative screening have been reported in same sex
      twins, presumptively due to fetal blood exchange. We report a case in which the
      diagnosis of congenital hypothyroidism due to thyroid ectopia in a monozygotic
      twin was delayed by 8 months, with a normal newborn screening TSH level of 11
      mIU/L blood (normal < 15 mIU/L) at 2 days of life. This is the first such case
      since the national New Zealand newborn screening programme introduced screening
      for congenital hypothyroidism in 1981 (30 years ago). Repeating thyroid studies
      at 14 days of age in same-sex twins has been advocated to avoid delayed
      diagnosis, but given the low risk, may not be cost effective. It is important to
      maintain a high index of suspicion in same-sex twin pregnancies of potential
      congenital hypothyroidism.

PMID- 22970837
TI  - Prevention of initial biofilm formation on ureteral stents using a sustained
      releasing varnish containing chlorhexidine: in vitro study.
AB  - BACKGROUND AND PURPOSE: Ureteral stents are being used exceedingly in the field
      of urology, and with advancements in endourology, this trend is increasing.
      Bacterial colonization and proliferation on the stent surface may result in
      urinary tract infections (UTIs) necessitating the administration of antibiotics
      that, in turn, may lead to the development of antibiotic-resistant bacterial
      strains. Several studies have shown that sustained release varnish (SRV) combined
      with antibiotics or antiseptics can prevent the proliferation of bacteria on
      urethral catheters. This is the first study that evaluates this technique
      implemented on ureteral stents. MATERIALS AND METHODS: We evaluated growth
      inhibition on ureteral stent segments coated with chlorhexidine (CHX) 1% SRV. The
      tests were conducted using common urinary pathogens: Enterococci, Pseudomonas,
      and Escherichia coli. Coated stent segments were inserted into bacterial
      suspensions. Controls included uncoated stent segments and stents coated with
      placebo SRV (without CHX). RESULTS: Bacterial growth measured as turbidity and as
      colony-forming units showed a significant inhibition effect of initial bacteria
      adhesion to the CHX-SRV coated stent segments compared with the controls
      (P<0.001). This inhibitory effect was apparent in each of the bacteria tested and
      was confirmed by inspection of the stent segments under an electron microscope.
      In a kinetic experiment using CHX 2% SRV, we were able to prolong the growth
      inhibition effect from 1 week to nearly 2 weeks. CONCLUSIONS: We believe this
      technique may play a significant role in reducing ureteral stent-associated UTIs.
      Further studies are needed before this approach can be implemented in clinical
      practice.

PMID- 22970838
TI  - An engineered diatom acting like a plasma cell secreting human IgG antibodies
      with high efficiency.
AB  - BACKGROUND: Although there are many different expression systems for recombinant
      production of pharmaceutical proteins, many of these suffer from drawbacks such
      as yield, cost, complexity of purification, and possible contamination with human
      pathogens. Microalgae have enormous potential for diverse biotechnological
      applications and currently attract much attention in the biofuel sector. Still
      underestimated, though, is the idea of using microalgae as solar-fueled
      expression system for the production of recombinant proteins. RESULTS: In this
      study, we show for the first time that completely assembled and functional human
      IgG antibodies can not only be expressed to high levels in algal systems, but
      also secreted very efficiently into the culture medium. We engineered the diatom
      Phaeodactylum tricornutum to synthesize and secrete a human IgG antibody against
      the Hepatitis B Virus surface protein. As the diatom P. tricornutum is not known
      to naturally secrete many endogenous proteins, the secreted antibodies are
      already very pure making extensive purification steps redundant and production
      extremely cost efficient. CONCLUSIONS: Microalgae combine rapid growth rates with
      all the advantages of eukaryotic expression systems, and offer great potential
      for solar-powered, low cost production of pharmaceutical proteins.

PMID- 22970839
TI  - The burden associated with neuropathic pain in Western Europe.
AB  - BACKGROUND: The purpose of this study is to assess the burden of neuropathic pain
      (NeP) on health-related quality-of-life (HRQoL), health status, employment
      status, absenteeism and presenteeism, and direct medical costs in Western Europe.
      METHODS: Data are from the 2010 National Health and Wellness Survey (NHWS) for
      five countries in western Europe: the UK, France, Spain, Germany, and Italy.
      Among subjects who reported experiencing pain in the past month, those who
      attributed their pain to NeP were compared with those who attributed their pain
      to another chronic pain condition other than NeP (the latter was the reference
      group). These two groups were compared on demographic and both pain and non-pain
      related comorbidities. Generalized linear models were used to estimate the
      independent contribution of the presence of NeP on: (a) HRQoL (using the SF
      12v2); (b) self-reported health status (the first item of the SF-12v2); (c)
      employment status; (d) absenteeism and presenteeism (using the WPAI
      questionnaire); and (e) direct medical costs (estimated from self-reported
      healthcare resource use and unit costs from the literature). RESULTS: Relative to
      the chronic pain reference group, subjects with NeP reported a higher prevalence
      of severe daily pain (38.12% vs 12.67%, p < 0.05), lower labor force
      participation (39.68% vs 55.56%; p < 0.05), higher prevalence of sleep
      difficulties (59.14% vs 46.73%; p < 0.05), insomnia (45.61% vs 29.78%; p < 0.05)
      anxiety (42.42% vs 31.99%; p < 0.05), and depression (35.25% vs 24.03%; p <
      0.05). NeP subjects reported higher rates of absenteeism (39.78% vs 21.47%; p <
      0.05) and presenteeism (86.48% vs. 66.70%; p < 0.050). Direct medical costs were
      approximately twice as high compared to non-NeP controls. In addition, >80% of
      NeP patients reported having other pain conditions. Regression results amplified
      these findings by indicating the independent contribution of confounding factors
      on the presence of NeP. LIMITATIONS: The NHWS is an Internet-based survey and may
      not be representative of the respective country populations if Internet access is
      limited. Second, respondents are asked to report their experience of pain.
      Although respondents are asked if their pain condition has been diagnosed by a
      physician there is no separate clinical confirmation of the presence of pain,
      pain conditions reported, and the presence of comorbidities. CONCLUSIONS: The
      presence of NeP is associated with an increased disease burden in the chronic
      pain population. This is seen in terms of HRQoL, health status, employment
      experience, and direct medical costs.

PMID- 22970840
TI  - Budget impact analysis of the use of oral and intravenous anti-cancer drugs for
      the treatment of HER2-positive metastatic breast cancer.
AB  - OBJECTIVES: Two anti-cancer drugs are currently approved for the treatment of
      HER2-positive metastatic breast cancer (MBC): trastuzumab-based therapy (TBT)
      administered intravenously as first line therapy until disease progression and
      lapatinib, an oral self-administered dual therapy with capecitabine (L+C) as
      second intention for patients who continue to progress despite TBT. In current
      practice, TBT is still prescribed beyond disease progression. In addition to
      medical reasons, the difficulty to switch eligible patients to oral drugs may
      also be explained by economic reasons. Thus, we aimed at comparing the budgetary
      impact of TBT and L+C for progressing HER2+MBC after TBT from the French Health
      Insurance perspective. METHODS: A budget impact analysis was performed on a 3
      year time horizon (2012-2014) to simulate a dynamic cohort of 4182 HER2-positive
      patients with a progressing MBC treated with TBT (73%) and L + C (27%). The model
      was adjusted on progression-free survival (PFS). Office visits, clinical
      evaluations, drug acquisition, administration costs, and transportation costs
      obtained from the literature and published databases were considered. RESULTS: In
      the base case analysis (2012), the annual treatment cost per patient for TBT
      (?36,077) was 2-times higher than that of L + C (?17,165). Using L + C for all
      patients (n = 4182) would avoid ?34.8 million of drug administration and
      transportation costs. Hospital costs represented 1% vs 88%, while community costs
      represented 99% vs 12% of L + C and TBT treatment costs, respectively. The lack
      of direct comparison PFS and treatment dosage modification data were the main
      limitations. However, no major changes from baseline results were observed from
      sensitivity analyses. CONCLUSIONS: Despite a slightly higher acquisition cost,
      the treatment cost of L + C remains lower than that of TBT, and it is the only
      approved anti-HER2 treatment for HER2-positive patients with progressing MBC.
      Based on this, it seems important to consider the potential savings for Health
      Insurance with the use of oral drug due to the reduction of outpatient
      hospitalizations. Such reductions may result in a subsequent budget reduction for
      hospitals, but may also provide those facing acute medical activity with
      opportunities to better manage other diseases whose treatment cannot be
      externalized.

PMID- 22970841
TI  - Digital slide imaging in cervicovaginal cytology: a pilot study.
AB  - CONTEXT: Digital whole slide imaging is the anticipated future of anatomic
      pathology, where sign-out of glass slides will be replaced by scanned images.
      Whole slide imaging has been successfully used in surgical pathology, but its
      usefulness and clinical application have been limited in cytology for several
      reasons, including lack of availability of z-axis depth focusing and large file
      size. Recently, several systems have become available in the United States for
      whole slide imaging with z-axis technology. OBJECTIVE: To determine the accuracy
      and efficiency of whole slide imaging, as compared with traditional glass slides,
      for use in cervicovaginal diagnostic cytology. DESIGN: Eleven cervicovaginal
      cytology cases (ThinPrep and SurePath) scanned at *20, *40, and *40 z-stack
      magnifications using the BioImagene iScan Coreo Au 3.0 scanner were evaluated by
      4 cytotechnologists and 3 pathologists in a blinded study. Different
      magnification scans were recorded as separate cases and presented in a randomized
      sequence. Corresponding glass slides were also reviewed. For each case, the
      diagnoses and total time to reach each diagnosis were recorded. RESULTS:
      Diagnostic accuracy was higher and average time per case was lower with glass
      slides as compared with all digital images. Among the digital images, the *40 or
      *40 z-stack had the highest diagnostic accuracy and lowest interpretation time.
      CONCLUSIONS: Whole slide imaging is a viable option for the purposes of teaching
      and consultations, and as a means of archiving cases. However, considering the
      large file size and total time to reach diagnosis on digital images, whole slide
      imaging is not yet ready for daily cervicovaginal diagnostic cytology screening
      use.

PMID- 22970843
TI  - Hepatic differentiation and maturation of human embryonic stem cells cultured in
      a perfused three-dimensional bioreactor.
AB  - Drug-induced liver injury is a serious and frequently occurring adverse drug
      reaction in the clinics and is hard to predict during preclinical studies. Today,
      primary hepatocytes are the most frequently used cell model for drug discovery
      and prediction of toxicity. However, their use is marred by high donor
      variability regarding drug metabolism and toxicity, and instable expression
      levels of liver-specific genes such as cytochromes P450. An in vitro model system
      based on human embryonic stem cells (hESC), with their unique properties of
      pluripotency and self-renewal, has potential to provide a stable and unlimited
      supply of human hepatocytes. Much effort has been made to direct hESC toward the
      hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results
      are encouraging, these cells lack important functionality. Here, we investigate
      if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D)
      bioreactor system. Human ESCs were differentiated toward the hepatic lineage
      using the same cells in either the 3D or 2D system. A global transcriptional
      analysis identified important differences between the 2 differentiation regimes,
      and we identified 10 pathways, highly related to liver functions, which were
      significantly upregulated in cells differentiated in the bioreactor compared to
      2D control cultures. The enhanced hepatic differentiation observed in the
      bioreactor system was also supported by immunocytochemistry. Taken together, our
      results suggest that hepatic differentiation of hESC is improved when using this
      3D bioreactor technology as compared to 2D culture systems.

PMID- 22970844
TI  - Chitosan: a new solution for removal of smear layer after root canal
      instrumentation.
AB  - AIM: To evaluate, by scanning electron microscopy (SEM), the efficacy of smear
      layer removal using chitosan compared with different chelating agents, and to
      quantify, by atomic absorption spectrophotometry with flame (AASF), the
      concentration of calcium ions in these solutions after irrigation. METHODOLOGY:
      The root canals of twenty-five canines were prepared using a crown-down technique
      and irrigated with 1% sodium hypochlorite. The teeth were randomly divided into
      groups (n = 5), according to the type of final irrigation: 15% EDTA, 0.2%
      chitosan, 10% citric acid, 1% acetic acid and control (without final irrigation).
      The total volume of each chelating solution was collected from the canals and
      analysed by AASF for quantification of calcium ions in the solutions. Then, the
      roots were split longitudinally and examined by SEM for evaluation of smear layer
      removal in the middle and apical thirds. Cleaning scores were attributed and
      analysed statistically using the Kruskal-Wallis and Dunn tests. The AASF data
      were analysed by one-way anova and Tukey-Kramer test. A significant level of
      alpha = 0.05 was adopted. RESULTS: 15% EDTA, 0.2% chitosan and 10% citric acid
      had similar smear layer removal capacity with a significant difference (P < 0.05)
      from 1% acetic acid and the control group. There was no significant difference (P
      > 0.05) between the smear layer remaining in the middle and apical thirds. The
      highest calcium ion concentration was observed with 15% EDTA (121.80 +/- 5.13)
      and 0.2% chitosan (104.13 +/- 19.23), with no significant difference. The lowest
      calcium ion concentration was obtained with 1% acetic acid (25.62 +/- 7.68),
      whilst 10% citric acid (70.38 +/- 11.15) had intermediate results, differing
      significantly from the other solutions (P < 0.01). CONCLUSIONS: 15% EDTA, 0.2%
      chitosan and 10% citric acid effectively removed smear layer from the middle and
      apical thirds of the root canal. 15% EDTA and 0.2% chitosan were associated with
      the greatest effect on root dentine demineralization, followed by 10% citric acid
      and 1% acetic acid.

PMID- 22970846
TI  - Expeditious microwave-assisted synthesis of 5-alkoxyoxazoles from alpha
      triflyloxy esters and nitriles.
AB  - A rapid and general access to diversely substituted 5-alkoxyoxazoles 2 (i.e.,
      R(1), R(2) = alkyl, phenyl) from easily accessible alpha-triflyloxy/hydroxy
      esters 1 and nitriles with good yields (41-76%) is reported. The versatility of
      the cyclization is shown for a range of substrates with high selectivity toward
      triflates over mesylates and proved to be compatible with sensitive functional
      groups. As an illustration of this transformation, the first synthesis of the
      recently isolated hydroxypyridine methyl multijuguinate 4 was achieved in four
      steps through a hetero Diels-Alder reaction of the 5-alkoxyoxazole and acrylic
      acid, followed by a protodecarboxylation reaction.

PMID- 22970842
TI  - Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011
      International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society classification.
AB  - The new International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society lung adenocarcinoma classification provides,
      for the first time, standardized terminology for lung cancer diagnosis in small
      biopsies and cytology; this was not primarily addressed by previous World Health
      Organization classifications. Until recently there have been no therapeutic
      implications to further classification of NSCLC, so little attention has been
      given to the distinction of adenocarcinoma and squamous cell carcinoma in small
      tissue samples. This situation has changed dramatically in recent years with the
      discovery of several therapeutic options that are available only to patients with
      adenocarcinoma or NSCLC, not otherwise specified, rather than squamous cell
      carcinoma. This includes recommendation for use of special stains as an aid to
      diagnosis, particularly in the setting of poorly differentiated tumors that do
      not show clear differentiation by routine light microscopy. A limited diagnostic
      workup is recommended to preserve as much tissue for molecular testing as
      possible. Most tumors can be classified using a single adenocarcinoma marker (eg,
      thyroid transcription factor 1 or mucin) and a single squamous marker (eg, p40 or
      p63). Carcinomas lacking clear differentiation by morphology and special stains
      are classified as NSCLC, not otherwise specified. Not otherwise specified
      carcinomas that stain with adenocarcinoma markers are classified as NSCLC, favor
      adenocarcinoma, and tumors that stain only with squamous markers are classified
      as NSCLC, favor squamous cell carcinoma. The need for every institution to
      develop a multidisciplinary tissue management strategy to obtain these small
      specimens and process them, not only for diagnosis but also for molecular testing
      and evaluation of markers of resistance to therapy, is emphasized.

PMID- 22970845
TI  - Cannabidivarin is anticonvulsant in mouse and rat.
AB  - BACKGROUND AND PURPOSE: Phytocannabinoids in Cannabis sativa have diverse
      pharmacological targets extending beyond cannabinoid receptors and several exert
      notable anticonvulsant effects. For the first time, we investigated the
      anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and
      in in vivo seizure models. EXPERIMENTAL APPROACH: The effect of CBDV (1-100 MUM)
      on epileptiform local field potentials (LFPs) induced in rat hippocampal brain
      slices by 4-aminopyridine (4-AP) application or Mg(2+) -free conditions was
      assessed by in vitro multi-electrode array recordings. Additionally, the
      anticonvulsant profile of CBDV (50-200 mg.kg(-1) ) in vivo was investigated in
      four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in
      mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The
      effects of CBDV in combination with commonly used antiepileptic drugs on rat
      seizures were investigated. Finally, the motor side effect profile of CBDV was
      investigated using static beam and grip strength assays. KEY RESULTS: CBDV
      significantly attenuated status epilepticus-like epileptiform LFPs induced by 4
      AP and Mg(2+) -free conditions. CBDV had significant anticonvulsant effects on
      the mES (>=100 mg.kg(-1) ), audiogenic (>=50 mg.kg(-1) ) and PTZ-induced seizures
      (>=100 mg.kg(-1) ). CBDV (200 mg.kg(-1) ) alone had no effect against pilocarpine
      induced seizures, but significantly attenuated these seizures when administered
      with valproate or phenobarbital at this dose. CBDV had no effect on motor
      function. CONCLUSIONS AND IMPLICATIONS: These results indicate that CBDV is an
      effective anticonvulsant in a broad range of seizure models. Also it did not
      significantly affect normal motor function and, therefore, merits further
      investigation as a novel anti-epileptic in chronic epilepsy models. LINKED
      ARTICLES: This article is part of a themed section on Cannabinoids. To view the
      other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue
      8.

PMID- 22970847
TI  - Expression of proliferative markers in ameloblastomas and malignant odontogenic
      tumors.
AB  - OBJECTIVE: To compare the proliferative activity in ameloblastoma and malignant
      odontogenic tumors, as assessed by Ki-67 immunostaining and determine whether
      expression of substance P (SP) and NK-1 receptor (NK-1R) is related to cell
      proliferation in these tumors. MATERIALS AND METHODS: Immunohistochemistry was
      used to evaluate protein expression in 44 benign and malignant odontogenic tumors
      from 39 patients. Immunohistochemistry was performed with anti-SP, anti-NK-1R,
      and anti-Ki-67 monoclonal antibodies, and the clinical and pathological data of
      the patients with odontogenic tumor were evaluated. RESULTS: Expression of Ki-67
      in malignant odontogenic tumors was significantly higher than in ameloblastomas
      (P < 0.001), and the expression level was associated with higher expression of NK
      1R. Among the ameloblastomas, there was significantly higher expression of Ki-67
      in peripheral ameloblastic-like cells (3.3 +/- 4.1) than in stellate reticulum
      like cells (2.6 +/- 3.7) (P = 0.04). In the majority of tissue locations of the
      malignant tumors, expression of SP and NK-1R was positively correlated with
      higher expression of Ki-67. CONCLUSION: These findings show that the expression
      level of Ki-67 in ameloblastomas was positively correlated with the rate of
      growth of odontogenic tumors. Overexpression of NK-1R complex in malignant
      odontogenic tumors could be part of the trigger stimulus that results in higher
      proliferative activity of the tumor.

PMID- 22970848
TI  - Methods for the drug effectiveness review project.
AB  - The Drug Effectiveness Review Project was initiated in 2003 in response to
      dramatic increases in the cost of pharmaceuticals, which lessened the purchasing
      power of state Medicaid budgets. A collaborative group of state Medicaid agencies
      and other organizations formed to commission high-quality comparative
      effectiveness reviews to inform evidence-based decisions about drugs that would
      be available to Medicaid recipients. The Project is coordinated by the Center for
      Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and
      the systematic reviews are undertaken by the Evidence-based Practice Centers
      (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to
      high standards for comparative effectiveness reviews. Because the investigators
      have direct, regular communication with policy-makers, the reports have direct
      impact on policy and decision-making, unlike many systematic reviews. The Project
      was an innovator of methods to involve stakeholders and continues to develop its
      methods in conducting reviews that are highly relevant to policy-makers. The
      methods used for selecting topics, developing key questions, searching,
      determining eligibility of studies, assessing study quality, conducting
      qualitative and quantitative syntheses, rating the strength of evidence, and
      summarizing findings are described. In addition, our on-going interactions with
      the policy-makers that use the reports are described.

PMID- 22970850
TI  - Biofortification of plants with altered antioxidant content and composition:
      genetic engineering strategies.
AB  - Antioxidants are protective molecules that neutralize reactive oxygen species and
      prevent oxidative damage to cellular components such as membranes, proteins and
      nucleic acids, therefore reducing the rate of cell death and hence the effects of
      ageing and ageing-related diseases. The fortification of food with antioxidants
      represents an overlap between two diverse environments, namely fortification of
      staple foods with essential nutrients that happen to have antioxidant properties
      (e.g. vitamins C and E) and the fortification of luxury foods with health
      promoting but non-essential antioxidants such as flavonoids as part of the
      nutraceuticals/functional foods industry. Although processed foods can be
      artificially fortified with vitamins, minerals and nutraceuticals, a more
      sustainable approach is to introduce the traits for such health-promoting
      compounds at source, an approach known as biofortification. Regardless of the
      target compound, the same challenges arise when considering the biofortification
      of plants with antioxidants, that is the need to modulate endogenous metabolic
      pathways to increase the production of specific antioxidants without affecting
      plant growth and development and without collateral effects on other metabolic
      pathways. These challenges become even more intricate as we move from the
      engineering of individual pathways to several pathways simultaneously. In this
      review, we consider the state of the art in antioxidant biofortification and
      discuss the challenges that remain to be overcome in the development of
      nutritionally complete and health-promoting functional foods.

PMID- 22970849
TI  - Modification of residue 42 of the active site loop with a lysine-mimetic side
      chain rescues isochorismate-pyruvate lyase activity in Pseudomonas aeruginosa
      PchB.
AB  - PchB is an isochorismate-pyruvate lyase from Pseudomonas aeruginosa. A positively
      charged lysine residue is located in a flexible loop that behaves as a lid to the
      active site, and the lysine residue is required for efficient production of
      salicylate. A variant of PchB that lacks the lysine at residue 42 has a reduced
      catalytic free energy of activation of up to 4.4 kcal/mol. Construction of a
      lysine isosteric residue bearing a positive charge at the appropriate position
      leads to the recovery of 2.5-2.7 kcal/mol (about 60%) of the 4.4 kcal/mol by
      chemical rescue. Exogenous addition of ethylamine to the K42A variant leads to a
      neglible recovery of activity (0.180 kcal/mol, roughly 7% rescue), whereas
      addition of propylamine caused an additional modest loss in catalytic power
      (0.056 kcal/mol, or 2% loss). This is consistent with the view that (a) the
      lysine-42 residue is required in a specific conformation to stabilize the
      transition state and (b) the correct conformation is achieved for a lysine
      mimetic side chain at site 42 in the course of loop closure, as expected for
      transition-state stabilization by the side chain ammonio function. That the
      positive charge is the main effector of transition state stabilization is shown
      by the construction of a lysine-isosteric residue capable of exerting steric
      effects and hydrogen bonding but not electrostatic effects, leading to a modest
      increase of catalytic power (0.267-0.505 kcal/mol of catalytic free energy, or
      roughly 6-11% rescue).

PMID- 22970851
TI  - Standard operating procedures for female orgasmic disorder: consensus of the
      International Society for Sexual Medicine.
AB  - INTRODUCTION: As the field of sexual medicine evolves, it is important to
      continually improve patient care by developing contemporary "standard operating
      procedures" (SOPs), reflecting the consensus view of experts in sexual medicine.
      Few, if any, consensus SOPs have been developed for the diagnosis and treatment
      of Female Orgasmic Disorder (FOD). AIM: The objective is to provide standard
      operating procedures for FOD. METHODS: The SOP Committee was composed of a chair,
      selected by the International Society for the Study of Sexual Medicine, and two
      additional experts. To inform its key recommendations, the Committee used
      systematic reviews of available evidence and discussions during a group meeting,
      conference calls and e-mail communications. The Committee received no corporate
      funding or remuneration. RESULTS: A total of 12 recommendations for the
      assessment and treatment of FOD were generated, including suggestions for further
      research. CONCLUSIONS: Evidence-based, practice recommendations for the treatment
      of FOD are provided that will hopefully inform clinical decision making for those
      treating this common condition.

PMID- 22970852
TI  - MpaA is a murein-tripeptide-specific zinc carboxypeptidase that functions as part
      of a catabolic pathway for peptidoglycan-derived peptides in gamma
      proteobacteria.
AB  - The murein peptide amidase MpaA is a cytoplasmic enzyme that processes peptides
      derived from the turnover of murein. We have purified the enzyme from Escherichia
      coli and demonstrated that it efficiently hydrolyses the gamma-D-glutamyl
      diaminopimelic acid bond in the murein tripeptide (L-Ala-gamma-D-Glu-meso-Dap),
      with Km and kcat values of 0.41+/-0.05 mM and 38.3+/-10 s-1. However, it is
      unable to act on the murein tetrapeptide (L-Ala-gamma-D-Glu-meso-Dap-D-Ala). E.
      coli MpaA is a homodimer containing one bound zinc ion per chain, as judged by
      mass spectrometric analysis and size-exclusion chromatography. To investigate the
      structure of MpaA we solved the crystal structure of the orthologous protein from
      Vibrio harveyi to 2.17 A (1A=0.1 nm). Vh_MpaA, which has identical enzymatic and
      biophysical properties to the E. coli enzyme, has high structural similarity to
      eukaryotic zinc carboxypeptidases. The structure confirms that MpaA is a dimeric
      zinc metalloprotein. Comparison of the structure of MpaA with those of other
      carboxypeptidases reveals additional structure that partially occludes the
      substrate-binding groove, perhaps explaining the narrower substrate specificity
      of the enzyme compared with other zinc carboxypeptidases. In gamma-proteobacteria
      mpaA is often located adjacent to mppA which encodes a periplasmic transporter
      protein previously shown to bind murein tripeptide. We demonstrate that MppA can
      also bind murein tetrapeptide with high affinity. The genetic coupling of these
      genes and their related biochemical functions suggest that MpaA amidase and MppA
      transporter form part of a catabolic pathway for utilization of murein-derived
      peptides that operates in gamma-proteobacteria in addition to the established
      murein recycling pathways.

PMID- 22970853
TI  - Proportion and extent of manifestation of molar-incisor-hypomineralizations
      according to different phenotypes.
AB  - OBJECTIVE: This epidemiological study aimed to assess the proportion and extent
      of manifestation of enamel hypomineralization, including molar-incisor
      hypomineralization (MIH), in the permanent and primary dentition. METHODS: A
      total of 693 children enrolled in an ongoing birth cohort study (GINIplus-10)
      were examined at their 10-year follow-up. Enamel hypomineralization was scored in
      the primary and permanent dentition on a tooth- and surface-related level based
      on the criteria of the European Academy of Paediatric Dentistry (EAPD). Children
      were grouped according to their distribution pattern of enamel
      hypomineralization: children with a minimum of one hypomineralized tooth in the
      primary dentition (ht >= 1) and permanent dentition (HT >= 1); with a minimum of
      one hypomineralization on at least one first permanent molar (MIH); and with
      hypomineralization on at least one first permanent molar and permanent incisor (M
      + IH). For each group, the mean values of hypomineralized primary teeth (ht),
      permanent teeth (HT), and permanent surfaces (HS) were calculated. RESULTS: The
      proportion of affected children was 36.5 percent (HT >= 1), 14.7 percent (MIH),
      and 9.4 percent (M + IH); 6.9 percent of the subjects had a minimum of one
      affected primary tooth (ht >= 1). The mean number of hypomineralized permanent
      teeth and surfaces were 2.3HT/2.9HS (HT >= 1), 3.4HT/4.8HS (MIH), and 4.2HT/5.9HS
      (M + IH). The mean number of hypomineralized primary teeth amounted to 0.1ht in
      the entire study population. CONCLUSIONS: Enamel hypomineralization can be
      detected frequently in this study sample. Children with M + IH showed the highest
      number of affected teeth and surfaces followed by those with MIH.

PMID- 22970854
TI  - GRID-based three-dimensional pharmacophores II: PharmBench, a benchmark data set
      for evaluating pharmacophore elucidation methods.
AB  - To date, published pharmacophore elucidation approaches typically use a handful
      of data sets for validation: here, we have assembled a data set for 81 targets,
      containing 960 ligands aligned using their cocrystallized protein targets, to
      provide the experimental "gold standard". The two-dimensional structures are also
      assembled to remove conformational bias; an ideal method would be able to take
      these structures as input, find the common features, and reproduce the bioactive
      conformations and their alignments to correspond with the X-ray-determined gold
      standard alignments. Here we present this data set and describe three objective
      measures to evaluate performance: the ability to identify the bioactive
      conformation, the ability to identify and correctly align this conformation for
      50% of the molecules in each data set, and the pharmacophoric field similarity.
      We have applied this validation methodology to our pharmacophore elucidation
      method FLAPpharm, that is published in the first paper of this series and discuss
      the limitations of the data set and objective success criteria. Starting from two
      dimensional structures and producing unbiased models, FLAPpharm was able to
      identify the bioactive conformations for 67% of the ligands and also to produce
      successful models according to the second metric for 67% of the Pharmbench data
      sets. Inspection of the unsuccessful models highlighted the limitation of this
      root mean square (rms)-derived metric, since many were found to be
      pharmacophorically reasonable, increasing the overall success rate to 83%. The
      PharmBench data set is available at http://www.moldiscovery.com/PharmBench ,
      along with a web service to enable users to score model alignments coming from
      external methods in the same way that we have presented here and, therefore,
      establishes a pharmacophore elucidation benchmark data set available to be used
      by the community.

PMID- 22970856
TI  - High-resolution imaging of basal cell carcinoma: a comparison between multiphoton
      microscopy with fluorescence lifetime imaging and reflectance confocal
      microscopy.
AB  - AIMS: The aim of this study was to compare morphological aspects of basal cell
      carcinoma (BCC) as assessed by two different imaging methods: in vivo reflectance
      confocal microscopy (RCM) and multiphoton tomography with fluorescence lifetime
      imaging implementation (MPT-FLIM). METHODS: The study comprised 16 BCCs for which
      a complete set of RCM and MPT-FLIM images were available. The presence of seven
      MPT-FLIM descriptors was evaluated. The presence of seven RCM equivalent
      parameters was scored in accordance to their extension. Chi-squared test with
      Fisher's exact test and Spearman's rank correlation coefficient were determined
      between MPT-FLIM scores and adjusted-RCM scores. RESULTS: MPT-FLIM and RCM
      descriptors of BCC were coupled to match the descriptors that define the same
      pathological structures. The comparison included: Streaming and Aligned elongated
      cells, Streaming with multiple directions and Double alignment, Palisading (RCM)
      and Palisading (MPT-FLIM), Typical tumor islands, and Cell islands surrounded by
      fibers, Dark silhouettes and Phantom islands, Plump bright cells and
      Melanophages, Vessels (RCM), and Vessels (MPT-FLIM). The parameters that were
      significantly correlated were Melanophages/Plump Bright Cells, Aligned elongated
      cells/Streaming, Double alignment/Streaming with multiple directions, and
      Palisading (MPT-FLIM)/Palisading (RCM). CONCLUSION: According to our data, both
      methods are suitable to image BCC's features. The concordance between MPT-FLIM
      and RCM is high, with some limitations due to the technical differences between
      the two devices. The hardest difficulty when comparing the images generated by
      the two imaging modalities is represented by their different field of view.

PMID- 22970855
TI  - Archaeal JAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin-like small
      archaeal modifier proteins (SAMPs) from protein-conjugates.
AB  - Proteins with JAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+) domains are widespread
      among all domains of life, yet poorly understood. Here we report the purification
      and characterization of an archaeal JAMM/MPN+ domain protein (HvJAMM1) from
      Haloferax volcanii that cleaves ubiquitin-like small archaeal modifier proteins
      (SAMP1/2) from protein conjugates. HvJAMM1 cleaved SAMP1/2 conjugates generated
      in H. volcanii as well as isopeptide- and linear-linked SAMP1-MoaE in purified
      form. Cleavage of linear linked SAMP1-MoaE was dependent on the presence of the
      SAMP domain and the C-terminal VSGG motif of this domain. While HvJAMM1 was
      inhibited by size exclusion chromatography and metal chelators, its activity
      could be restored by addition of excess ZnCl2 . HvJAMM1 residues (Glu31, His88,
      His90, Ser98 and Asp101) that were conserved with the JAMM/MPN+ active-site motif
      were required for enzyme activity. Together, these results provide the first
      example of a JAMM/MPN+ zinc metalloprotease that independently catalyses the
      cleavage of ubiquitin-like (isopeptide and linear) bonds from target proteins. In
      archaea, HvJAMM1 likely regulates sampylation and the pools of 'free' SAMP
      available for protein modification. HvJAMM1-type proteins are thought to release
      the SAMPs from proteins modified post-translationally as well as those
      synthesized as domain fusions.

PMID- 22970857
TI  - Identification of a role for a mouse sperm surface aldo-keto reductase (AKR1B7)
      and its human analogue in the detoxification of the reactive aldehyde, acrolein.
AB  - Mouse vas deferens protein (AKR1B7), a member of the aldo-keto reductase family,
      was purified to homogeneity. Antibodies raised to AKR1B7 revealed an aldo-keto
      reductase on the human sperm surface, while confocal microscopy experiments
      demonstrated that this enzyme covered the entire human sperm surface and was
      concentrated on the mid-piece. Further functional characterisation of a
      recombinant form of AKR1B7 showed that the likely role of AKR1B7 is the reduction
      of the reactive aldehyde, acrolein, a by-product of spermine catabolism in the
      reproductive tract. A similar acrolein detoxification activity was displayed by
      human sperm membrane extracts but was not present in seminal plasma. These
      results indicate that human sperm possess an aldo-keto reductase on their
      membrane surface and are thus enzymatically protected against reactive aldehyde
      species both in the male and female reproductive tract. 

PMID- 22970858
TI  - Genetic toxicology of thallium: a review.
AB  - This review summarizes the current knowledge about the general toxicity of
      thallium (Tl) and its environmental sources, with special emphasis placed on its
      potential mutagenic, genotoxic, and cytotoxic effects on both eukaryotic and
      prokaryotic cells. Tl is a nonessential heavy metal that poses environmental and
      occupational threats as well as therapeutic hazards because of its use in
      medicine. It is found in two oxidation states, thallous (Tl(+)) and thallic
      (Tl(3+)), both of which are considered highly toxic to human beings and domestic
      and wild organisms. Many Tl compounds are colorless, odorless and tasteless, and
      these characteristics, combined with the high toxicity of TI compounds, have led
      to their use as poisons. Because of its similarity to potassium ions (K(+)),
      plants and mammals readily absorb Tl(+) through the skin and digestive and
      respiratory systems. In mammals, it can cross the placental, hematoencephalic,
      and gonadal barriers. Inside cells, Tl can accumulate and interfere with the
      metabolism of potassium and other metal cations, mimicking or inhibiting their
      action. The effects of Tl on genetic material have not yet been thoroughly
      explored, and few existing studies have focused exclusively on Tl(+). Both in
      vivo and in vitro studies indicate that Tl compounds can have a weak mutagenic
      effect, but no definitive effect on the induction of primary DNA damage or
      chromosomal damage has been shown. These studies have demonstrated that Tl
      compounds are highly toxic and lead to changes in cell-cycle progression.

PMID- 22970859
TI  - Evidence for the use of  vilazodone  in the treatment of major depressive
      disorder.
AB  - INTRODUCTION: Major depressive disorder (MDD) is characterized by dysfunction in
      cognition, behavior, and physical functioning, and is associated with a chronic
      clinical course. There are barriers to successful treatment, which often result
      in early discontinuation and relapse. Adverse effects (AEs) remain the most
      commonly cited reason for discontinuation of treatment with conventional
      antidepressants, particularly early on in therapy. This often translates into
      relapse of symptoms or recurrence of the depressive episode. The delay to
      therapeutic response also has a meaningful implication for treatment adherence.
      AREAS COVERED: This article focuses on the implications of a novel entity for the
      treatment of depression; the first new molecule developed for this indication in
      the last 10 years. Vilazodone is a novel dual-acting serotonergic antidepressant,
      which is a selective and potent inhibitor of serotonin reuptake, as well as a
      selective partial agonist of the 5-HT(1A) receptor. EXPERT OPINION: The data
      available in the literature so far indicate clinical efficacy over placebo and a
      rather benign adverse event profile. Whether the early onset of clinical efficacy
      observed in one of the two pivotal studies represents a true or only a chance
      phenomenon, only future studies can tell. Adverse effects are mostly mild
      moderate and most GI type AEs disappear in about one week, at a time when all
      patients are still on a clinically suboptimal daily dosage (10 mg/d during the
      first week). Sexual AEs did not differ from placebo. Vilazodone represents an
      interesting addition to the arsenal of available antidepressants.

PMID- 22970860
TI  - Is more always better in cataract surgery?

PMID- 22970861
TI  - Controlling the nanostructure of gold nanorod-lyotropic liquid-crystalline hybrid
      materials using near-infrared laser irradiation.
AB  - Lipid-based liquid-crystalline matrixes provide a unique prospect for stimuli
      responsive nanomaterials, attributed to the ability to effect self-assembly of
      the lipids at the molecular level. Differences in liquid crystal nanostructure
      have previously been shown to change drug diffusion and hence release, with
      research progressing toward the use of in situ changes to nanostructure to
      control drug release. Toward this goal, we have previously communicated the
      ability to switch between nonlamellar structures using gold nanorod (GNR)
      phytantriol-based liquid-crystalline hybrid nanomaterials as near-infrared light
      responsive systems (Fong et al. Langmuir 2010, 26, 6136-6139). In this study, the
      effect of laser activation on matrix nanostructure with changes in a number of
      system variables including lipid composition, GNR aspect ratio, GNR
      concentration, and laser pulse time were investigated. The nanostructure of the
      matrix was followed using small-angle X-ray scattering, while both cryoFESEM and
      cryoTEM were used to visualize the effect of GNR incorporation into the liquid
      crystal nanostructure. The system response was found to be dependent on all
      variables, thus demonstrating the potential of these nanocomposite materials as
      reversible "on-demand" drug delivery applications.

PMID- 22970862
TI  - Programmable hydrogels for controlled cell catch and release using hybridized
      aptamers and complementary sequences.
AB  - The ability to regulate cell-material interactions is important in various
      applications such as regenerative medicine and cell separation. This study
      successfully demonstrates that the binding states of cells on a hydrogel surface
      can be programmed by using hybridized aptamers and triggering complementary
      sequences (CSs). In the absence of the triggering CSs, the aptamers exhibit a
      stable, hybridized state in the hydrogel for cell-type-specific catch. In the
      presence of the triggering CSs, the aptamers are transformed into a new
      hybridized state that leads to the rapid dissociation of the aptamers from the
      hydrogel. As a result, the cells are released from the hydrogel. The entire
      procedure of cell catch and release during the transformation of the aptamers is
      biocompatible and does not involve any factor destructive to either the cells or
      the hydrogel. Thus, the programmable hydrogel is regenerable and can be applied
      to a new round of cell catch and release when needed.

PMID- 22970863
TI  - LIFE: Life Investigation For Enceladus  A Sample Return Mission Concept in Search
      for Evidence of Life.
AB  - Life Investigation For Enceladus (LIFE) presents a low-cost sample return mission
      to Enceladus, a body with high astrobiological potential. There is ample evidence
      that liquid water exists under ice coverage in the form of active geysers in the
      "tiger stripes" area of the southern Enceladus hemisphere. This active plume
      consists of gas and ice particles and enables the sampling of fresh materials
      from the interior that may originate from a liquid water source. The particles
      consist mostly of water ice and are 1-10 MU in diameter. The plume composition
      shows H(2)O, CO(2), CH(4), NH(3), Ar, and evidence that more complex organic
      species might be present. Since life on Earth exists whenever liquid water,
      organics, and energy coexist, understanding the chemical components of the
      emanating ice particles could indicate whether life is potentially present on
      Enceladus. The icy worlds of the outer planets are testing grounds for some of
      the theories for the origin of life on Earth. The LIFE mission concept is
      envisioned in two parts: first, to orbit Saturn (in order to achieve lower
      sampling speeds, approaching 2 km/s, and thus enable a softer sample collection
      impact than Stardust, and to make possible multiple flybys of Enceladus); second,
      to sample Enceladus' plume, the E ring of Saturn, and the Titan upper atmosphere.
      With new findings from these samples, NASA could provide detailed chemical and
      isotopic and, potentially, biological compositional context of the plume. Since
      the duration of the Enceladus plume is unpredictable, it is imperative that these
      samples are captured at the earliest flight opportunity. If LIFE is launched
      before 2019, it could take advantage of a Jupiter gravity assist, which would
      thus reduce mission lifetimes and launch vehicle costs. The LIFE concept offers
      science returns comparable to those of a Flagship mission but at the measurably
      lower sample return costs of a Discovery-class mission.

PMID- 22970864
TI  - Using a mini-Raman spectrometer to monitor the adaptive strategies of
      extremophile colonizers in arid deserts: relationships between signal strength,
      adaptive strategies, solar radiation, and humidity.
AB  - The survival strategies of one cyanobacteria colony and three terricolous lichen
      species from the hot subdesert of Tabernas, Spain, were studied along with
      topographical attributes of the area to investigate whether the protective
      strategies adopted by these pioneer soil colonizers are related to the
      environmental stressors under which they survive. A handheld Raman spectrometer
      was used for biomolecular characterization, while the microclimatic and
      topographic parameters were estimated with a Geographic Information System (GIS).
      We found that the survival strategies adopted by those organisms are based on
      different combinations of protective biomolecules, each with diverse
      ecophysiological functions, such as UV-radiation screening, free-energy
      quenching, antioxidants, and the production of different types and amounts of
      calcium oxalates. Our results show that the cyanobacteria community and each
      lichen species preferentially colonized a particular microhabitat with specific
      moisture and incident solar radiation levels and exhibited different adaptive
      mechanisms. In recent years, a number of studies have provided consistent results
      that suggest a link between the strategies adopted by those extremophile
      organisms and the microclimatic environmental parameters. To date, however, far
      too little attention has been paid to results from Raman analyses on dry
      specimens. Therefore, the results of the present study, produced with the use of
      our miniaturized instrument, will be of interest to future studies in
      astrobiology, especially due to the likely use of Raman spectroscopy at the
      surface of Mars.

PMID- 22970866
TI  - Modified superparamagnetic nanocomposite microparticles for highly selective
      Hg(II) or Cu(II) separation and recovery from aqueous solutions.
AB  - The synthesis of a reusable, magnetically switchable nanocomposite microparticle,
      which can be modified to selectively extract and recover Hg(II) or Cu(II) from
      water, is reported. Superparamagnetic iron oxide (magnetite) nanoparticles act as
      the magnetic component in this system, and these nanoparticles were synthesized
      in a continuous way, allowing their large-scale production. A new process was
      used to create a silica matrix, confining the magnetite nanoparticles using a
      cheap silica source [sodium silicate (water glass)]. This results in a well
      defined, filigree micrometer-sized nanocomposite via a fast, simple, inexpensive,
      and upscalable process. Hence, because of the ideal size of the resulting
      microparticles and their comparably large magnetization, particle extraction from
      fluids by low-cost magnets is achieved.

PMID- 22970865
TI  - Oxygen and hydrogen peroxide in the early evolution of life on earth: in silico
      comparative analysis of biochemical pathways.
AB  - In the Universe, oxygen is the third most widespread element, while on Earth it
      is the most abundant one. Moreover, oxygen is a major constituent of all
      biopolymers fundamental to living organisms. Besides O(2), reactive oxygen
      species (ROS), among them hydrogen peroxide (H(2)O(2)), are also important
      reactants in the present aerobic metabolism. According to a widely accepted
      hypothesis, aerobic metabolism and many other reactions/pathways involving O(2)
      appeared after the evolution of oxygenic photosynthesis. In this study, the
      hypothesis was formulated that the Last Universal Common Ancestor (LUCA) was at
      least able to tolerate O(2) and detoxify ROS in a primordial environment. A
      comparative analysis was carried out of a number of the O(2)-and H(2)O(2)
      involving metabolic reactions that occur in strict anaerobes, facultative
      anaerobes, and aerobes. The results indicate that the most likely LUCA possessed
      O(2)-and H(2)O(2)-involving pathways, mainly reactions to remove ROS, and had, at
      least in part, the components of aerobic respiration. Based on this, the presence
      of a low, but significant, quantity of H(2)O(2) and O(2) should be taken into
      account in theoretical models of the early Archean atmosphere and oceans and the
      evolution of life. It is suggested that the early metabolism involving
      O(2)/H(2)O(2) was a key adaptation of LUCA to already existing weakly oxic zones
      in Earth's primordial environment.

PMID- 22970867
TI  - Active subspace: toward scalable low-rank learning.
AB  - We address the scalability issues in low-rank matrix learning problems. Usually
      these problems resort to solving nuclear norm regularized optimization problems
      (NNROPs), which often suffer from high computational complexities if based on
      existing solvers, especially in large-scale settings. Based on the fact that the
      optimal solution matrix to an NNROP is often low rank, we revisit the classic
      mechanism of low-rank matrix factorization, based on which we present an active
      subspace algorithm for efficiently solving NNROPs by transforming large-scale
      NNROPs into small-scale problems. The transformation is achieved by factorizing
      the large solution matrix into the product of a small orthonormal matrix (active
      subspace) and another small matrix. Although such a transformation generally
      leads to nonconvex problems, we show that a suboptimal solution can be found by
      the augmented Lagrange alternating direction method. For the robust PCA (RPCA)
      (Candes, Li, Ma, & Wright,  2009 ) problem, a typical example of NNROPs,
      theoretical results verify the suboptimality of the solution produced by our
      algorithm. For the general NNROPs, we empirically show that our algorithm
      significantly reduces the computational complexity without loss of optimality.

PMID- 22970868
TI  - Self-consistent learning of the environment.
AB  - We study the Bayesian process to estimate the features of the environment. We
      focus on two aspects of the Bayesian process: how estimation error depends on the
      prior distribution of features and how the prior distribution can be learned from
      experience. The accuracy of the perception is underestimated when each feature of
      the environment is considered independently because many different features of
      the environment are usually highly correlated and the estimation error greatly
      depends on the correlations. The self-consistent learning process renews the
      prior distribution of correlated features jointly with the estimation of the
      environment. Here, maximum a posteriori probability (MAP) estimation decreases
      the effective dimensions of the feature vector. There are critical noise levels
      in self-consistent learning with MAP estimation, that cause hysteresis behaviors
      in learning. The self-consistent learning process with stochastic Bayesian
      estimation (SBE) makes the presumed distribution of environmental features
      converge to the true distribution for any level of channel noise. However, SBE is
      less accurate than MAP estimation. We also discuss another stochastic method of
      estimation, SBE2, which has a smaller estimation error than SBE without
      hysteresis.

PMID- 22970869
TI  - The shape of phase-resetting curves in oscillators with a saddle node on an
      invariant circle bifurcation.
AB  - We introduce a simple two-dimensional model that extends the Poincare oscillator
      so that the attracting limit cycle undergoes a saddle node bifurcation on an
      invariant circle (SNIC) for certain parameter values. Arbitrarily close to this
      bifurcation, the phase-resetting curve (PRC) continuously depends on parameters,
      where its shape can be not only primarily positive or primarily negative but also
      nearly sinusoidal. This example system shows that one must be careful inferring
      anything about the bifurcation structure of the oscillator from the shape of its
      PRC.

PMID- 22970870
TI  - Statistical computer model analysis of the reciprocal and recurrent inhibitions
      of the Ia-EPSP in alpha-motoneurons.
AB  - We simulate the inhibition of Ia-glutamatergic excitatory postsynaptic potential
      (EPSP) by preceding it with glycinergic recurrent (REN) and reciprocal (REC)
      inhibitory postsynaptic potentials (IPSPs). The inhibition is evaluated in the
      presence of voltage-dependent conductances of sodium, delayed rectifier
      potassium, and slow potassium in five alpha-motoneurons (MNs). We distribute the
      channels along the neuronal dendrites using, alternatively, a density function of
      exponential rise (ER), exponential decay (ED), or a step function (ST). We
      examine the change in EPSP amplitude, the rate of rise (RR), and the time
      integral (TI) due to inhibition. The results yield six major conclusions. First,
      the EPSP peak and the kinetics depending on the time interval are either
      amplified or depressed by the REC and REN shunting inhibitions. Second, the mean
      EPSP peak, its TI, and RR inhibition of ST, ER, and ED distributions turn out to
      be similar for analogous ranges of G. Third, for identical G, the large
      variations in the parameters' values can be attributed to the sodium conductance
      step (g(Na_step)) and the active dendritic area. We find that small g(Na_step) on
      a few dendrites maintains the EPSP peak, its TI, and RR inhibition similar to the
      passive state, but high g(Na_step) on many dendrites decrease the inhibition and
      sometimes generates even an excitatory effect. Fourth, the MN's input resistance
      does not alter the efficacy of EPSP inhibition. Fifth, the REC and REN
      inhibitions slightly change the EPSP peak and its RR. However, EPSP TI is
      depressed by the REN inhibition more than the REC inhibition. Finally, only an
      inhibitory effect shows up during the EPSP TI inhibition, while there are both
      inhibitory and excitatory impacts on the EPSP peak and its RR.

PMID- 22970871
TI  - A compartmental model of linear resonance and signal transfer in dendrites.
AB  - Dendrites carry signals between synapses and the soma and play a central role in
      neural computation. Although they contain many nonlinear ion channels, their
      signal-transfer properties are linear under some experimental conditions. In
      experiments with continuous-time inputs, a resonant linear two-port model has
      been shown to provide a near-perfect fit to the dendrite-to-soma input-output
      relationship. In this study, we focused on this linear aspect of signal transfer
      using impedance functions that replace biophysical channel models in order to
      describe the electrical properties of the dendritic membrane. The membrane
      impedance model of dendrites preserves the accuracy of the two-port model with
      minimal computational complexity. Using this approach, we demonstrate two
      membrane impedance profiles of dendrites that reproduced the experimentally
      observed two-port results. These impedance profiles demonstrate that the two-port
      results are compatible with different computational schemes. In addition, our
      model highlights how dendritic resonance can minimize the location-dependent
      attenuation of signals at the resonant frequency. Thus, in this model, dendrites
      function as linear-resonant filters that carry signals between nonlinear
      computational units.

PMID- 22970872
TI  - Design strategies for weight matrices of echo state networks.
AB  - This article develops approaches to generate dynamical reservoirs of echo state
      networks with desired properties reducing the amount of randomness. It is
      possible to create weight matrices with a predefined singular value spectrum. The
      procedure guarantees stability (echo state property). We prove the minimization
      of the impact of noise on the training process. The resulting reservoir types are
      strongly related to reservoirs already known in the literature. Our experiments
      show that well-chosen input weights can improve performance.

PMID- 22970873
TI  - Tangent bundle curve completion with locally connected parallel networks.
AB  - We propose a theory for cortical representation and computation of visually
      completed curves that are generated by the visual system to fill in missing
      visual information (e.g., due to occlusions). Recent computational theories and
      physiological evidence suggest that although such curves do not correspond to
      explicit image evidence along their length, their construction emerges from
      corresponding activation patterns of orientation-selective cells in the primary
      visual cortex. Previous theoretical work modeled these patterns as least
      energetic 3D curves in the mathematical continuous space R2 * S1, which abstracts
      the mammalian striate cortex. Here we discuss the biological plausibility of this
      theory and present a neural architecture that implements it with locally
      connected parallel networks. Part of this contribution is also a first attempt to
      bridge the physiological literature on curve completion with the shape problem
      and a shape theory. We present completion simulations of our model in natural and
      synthetic scenes and discuss various observations and predictions that emerge
      from this theory in the context of curve completion.

PMID- 22970875
TI  - Linear coordinate-descent message passing for quadratic optimization.
AB  - In this letter, we propose a new message-passing algorithm for quadratic
      optimization. The design of the new algorithm is based on linear coordinate
      descent between neighboring nodes. The updating messages are in a form of linear
      functions as compared to the min-sum algorithm of which the messages are in a
      form of quadratic functions. As a result, the linear coordinate-descent (LiCD)
      algorithm transmits only one parameter per message as opposed to the min-sum
      algorithm, which transmits two parameters per message. We show that when the
      quadratic matrix is walk-summable, the LiCD algorithm converges. By taking the
      LiCD algorithm as a subroutine, we also fix the convergence issue for a general
      quadratic matrix. The LiCD algorithm works in either a synchronous or
      asynchronous message-passing manner. Experimental results show that for a general
      graph with multiple cycles, the LiCD algorithm has comparable convergence speed
      to the min-sum algorithm, thereby reducing the number of parameters to be
      transmitted and the computational complexity.

PMID- 22970874
TI  - Tuning low-voltage-activated A-current for silent gain modulation.
AB  - Modulation of stimulus-response gain and stability of spontaneous (unstimulated)
      firing are both important for neural computation. However, biologically plausible
      mechanisms that allow these distinct functional capabilities to coexist in the
      same neuron are poorly defined. Low-threshold, inactivating (A-type) K(+)
      currents (I(A)) are found in many biological neurons and are historically known
      for enabling low-frequency firing. By performing simulations using a conductance
      based model neuron, here we show that biologically plausible shifts in I(A)
      conductance and inactivation kinetics produce dissociated effects on gain and
      intrinsic firing. This enables I(A) to regulate gain without major changes in
      intrinsic firing rate. Tuning I(A) properties may thus represent a previously
      unsuspected single-current mechanism of silent gain control in neurons.

PMID- 22970876
TI  - A common network architecture efficiently implements a variety of sparsity-based
      inference problems.
AB  - The sparse coding hypothesis has generated significant interest in the
      computational and theoretical neuroscience communities, but there remain open
      questions about the exact quantitative form of the sparsity penalty and the
      implementation of such a coding rule in neurally plausible architectures. The
      main contribution of this work is to show that a wide variety of sparsity-based
      probabilistic inference problems proposed in the signal processing and statistics
      literatures can be implemented exactly in the common network architecture known
      as the locally competitive algorithm (LCA). Among the cost functions we examine
      are approximate l(p) norms (0 <= p <= 2), modified l(p)-norms, block-l1 norms,
      and reweighted algorithms. Of particular interest is that we show significantly
      increased performance in reweighted l1 algorithms by inferring all parameters
      jointly in a dynamical system rather than using an iterative approach native to
      digital computational architectures.

PMID- 22970877
TI  - Information-geometric measures for estimation of connection weight under
      correlated inputs.
AB  - The brain processes information in a highly parallel manner. Determination of the
      relationship between neural spikes and synaptic connections plays a key role in
      the analysis of electrophysiological data. Information geometry (IG) has been
      proposed as a powerful analysis tool for multiple spike data, providing useful
      insights into the statistical interactions within a population of neurons.
      Previous work has demonstrated that IG measures can be used to infer the
      connection weight between two neurons in a neural network. This property is
      useful in neuroscience because it provides a way to estimate learning-induced
      changes in synaptic strengths from extracellular neuronal recordings. A previous
      study has shown, however, that this property would hold only when inputs to
      neurons are not correlated. Since neurons in the brain often receive common
      inputs, this would hinder the application of the IG method to real data. We
      investigated the two-neuron-IG measures in higher-order log-linear models to
      overcome this limitation. First, we mathematically showed that the estimation of
      uniformly connected synaptic weight can be improved by taking into account higher
      order log-linear models. Second, we numerically showed that the estimation can be
      improved for more general asymmetrically connected networks. Considering the
      estimated number of the synaptic connections in the brain, we showed that the two
      neuron IG measure calculated by the fourth- or fifth-order log-linear model would
      provide an accurate estimation of connection strength within approximately a 10%
      error. These studies suggest that the two-neuron IG measure with higher-order log
      linear expansion is a robust estimator of connection weight even under correlated
      inputs, providing a useful analytical tool for real multineuronal spike data.

PMID- 22970878
TI  - Pavlov's dog associative learning demonstrated on synaptic-like organic
      transistors.
AB  - In this letter, we present an original demonstration of an associative learning
      neural network inspired by the famous Pavlov's dogs experiment. A single
      nanoparticle organic memory field effect transistor (NOMFET) is used to implement
      each synapse. We show how the physical properties of this dynamic memristive
      device can be used to perform low-power write operations for the learning and
      implement short-term association using temporal coding and spike-timing-dependent
      plasticity-based learning. An electronic circuit was built to validate the
      proposed learning scheme with packaged devices, with good reproducibility despite
      the complex synaptic-like dynamic of the NOMFET in pulse regime.

PMID- 22970879
TI  - ANUBIS: artificial neuromodulation using a Bayesian inference system.
AB  - Gain tuning is a crucial part of controller design and depends not only on an
      accurate understanding of the system in question, but also on the designer's
      ability to predict what disturbances and other perturbations the system will
      encounter throughout its operation. This letter presents ANUBIS (artificial
      neuromodulation using a Bayesian inference system), a novel biologically inspired
      technique for automatically tuning controller parameters in real time. ANUBIS is
      based on the Bayesian brain concept and modifies it by incorporating a model of
      the neuromodulatory system comprising four artificial neuromodulators. It has
      been applied to the controller of EchinoBot, a prototype walking rover for
      Martian exploration. ANUBIS has been implemented at three levels of the
      controller; gait generation, foot trajectory planning using Bezier curves, and
      foot trajectory tracking using a terminal sliding mode controller. We compare the
      results to a similar system that has been tuned using a multilayer perceptron.
      The use of Bayesian inference means that the system retains mathematical
      interpretability, unlike other intelligent tuning techniques, which use neural
      networks, fuzzy logic, or evolutionary algorithms. The simulation results show
      that ANUBIS provides significant improvements in efficiency and adaptability of
      the three controller components; it allows the robot to react to obstacles and
      uncertainties faster than the system tuned with the MLP, while maintaining
      stability and accuracy. As well as advancing rover autonomy, ANUBIS could also be
      applied to other situations where operating conditions are likely to change or
      cannot be accurately modeled in advance, such as process control. In addition, it
      demonstrates one way in which neuromodulation could fit into the Bayesian brain
      framework.

PMID- 22970881
TI  - Temporal trends in severe malaria in Chittagong, Bangladesh.
AB  - BACKGROUND: Epidemiological data on malaria in Bangladesh are sparse,
      particularly on severe and fatal malaria. This hampers the allocation of
      healthcare provision in this resource-poor setting. Over 85% of the estimated
      150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division
      with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital
      (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong
      Division. METHODS: Malaria screening data from 22,785 inpatients in CMCH from
      1999-2011 were analysed to investigate the patterns of referral, temporal trends
      and geographical distribution of severe malaria in Chittagong Division,
      Bangladesh. RESULTS: From 1999 till 2011, 2,394 malaria cases were admitted, of
      which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was
      commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria
      incidence was marked with a single peak in P. falciparum transmission from June
      to August coinciding with peak rainfall, whereas P. vivax showed an additional
      peak in February-March possibly representing relapse infections. Since 2007 there
      has been a substantial decrease in the absolute number of admitted malaria cases.
      Case fatality in severe malaria was 18% from 2008-2011, remaining steady during
      this period.A travel history obtained in 226 malaria patients revealed only 33%
      had been to the CHT in the preceding three weeks. Of all admitted malaria
      patients, only 9% lived in the CHT, and none in the more remote malaria endemic
      regions near the Indian border. CONCLUSIONS: The overall decline in admitted
      malaria cases to CMCH suggests recent control measures are successful. However,
      there are no reliable data on the incidence of severe malaria in the CHT, the
      most endemic area of Bangladesh, and most of these patients do not reach tertiary
      health facilities. Improvement of early treatment and simple supportive care for
      severe malaria in remote areas and implementation of a referral system for cases
      requiring additional supportive care could be important contributors to further
      reducing malaria-attributable disease and death in Bangladesh.

PMID- 22970880
TI  - Biopolymer-connected liposome networks as injectable biomaterials capable of
      sustained local drug delivery.
AB  - Biopolymers bearing hydrophobic side-chains, such as hydrophobically modified
      chitosan (hmC), can connect liposomes into a gel network via hydrophobic
      interactions. In this paper, we show that such liposome gels possess an
      attractive combination of properties for certain drug delivery applications.
      Their shear-thinning property allows these gels to be injected at a particular
      site, while their gel-like nature at rest ensures that the material will remain
      localized at that site. Moreover, drugs can be encapsulated in the interior of
      the liposomes and delivered at the local site for an extended period of time. The
      presence of two transport resistances - from the liposomal bilayer and the gel
      network - is shown to be responsible for the sustained release; in turn,
      disruption of the liposomes both weakens the gel and causes a faster release. We
      have monitored release kinetics from liposome gels of a cationic anticancer drug
      doxorubicin (Dox) encapsulated in liposomes. Sustained release of Dox from these
      gels and the concomitant cytotoxic effect could be observed for over a week.

PMID- 22970883
TI  - Synthesis of (-)-oseltamivir phosphate (Tamiflu) starting from cis-2,3
      bis(hydroxymethyl)aziridine.
AB  - Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3
      bis(hydroxymethyl)aziridine. After protection of the cis-2,3
      bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral
      aziridine, which was a key intermediate to install the required stereogenic
      center containing a nitrogen atom. Allylation and ring closing metathesis are the
      key reactions to obtain the cyclic product that was successfully converted to the
      desired oseltamivir phosphate.

PMID- 22970882
TI  - Juvenile Parkinsonism.
AB  - We present the case of a 14-year-old boy presented with a recent history of
      progressive neurologic decline and extrapyramidal features. The history and
      findings with illustrative figures are detailed, and a diagnostic approach to the
      presentation is considered. The therapeutic options and broader management issues
      are briefly reviewed.

PMID- 22970884
TI  - Time-resolved characterization of primary emissions from residential wood
      combustion appliances.
AB  - Primary emissions from a log wood burner and a pellet boiler were characterized
      by online measurements of the organic aerosol (OA) using a high-resolution time
      of-flight aerosol mass spectrometer (HR-TOF-AMS) and of black carbon (BC). The OA
      and BC concentrations measured during the burning cycle of the log wood burner,
      batch wise fueled with wood logs, were highly variable and generally dominated by
      BC. The emissions of the pellet burner had, besides inorganic material, a high
      fraction of OA and a minor contribution of BC. However, during artificially
      induced poor burning BC was the dominating species with ~80% of the measured
      mass. The elemental O:C ratio of the OA was generally found in the range of 0.2
      0.5 during the startup phase or after reloading of the log wood burner. During
      the burnout or smoldering phase, O:C ratios increased up to 1.6-1.7, which is
      similar to the ratios found for the pellet boiler during stable burning
      conditions and higher than the O:C ratios observed for highly aged ambient OA.
      The organic emissions of both burners have a very similar H:C ratio at a given
      O:C ratio and therefore fall on the same line in the Van Krevelen diagram.

PMID- 22970885
TI  - Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope
      restoration after transgenic ablation.
AB  - In a recent study, we showed that the adult pituitary gland is capable of
      regenerating transgenically ablated growth hormone-producing (GH(+))
      somatotropes. Here, we investigated whether the gland's regenerative capacity is
      more general and also applies to the other major hormonal cell type, the
      prolactin-producing (PRL(+)) lactotropes. We set up the transgenic
      PRLCre/inducible diphtheria toxin receptor (iDTR) mouse model, in which the PRL
      promoter drives expression of Cre that induces DTR in lactotropes. Injection of
      female mice with DT for different periods causes a gradual ablation of PRL(+)
      cells, reaching a maximum of 70% after 10-day DT treatment. During the following
      weeks, lactotropes progressively reappear achieving a 60% restoration after 6
      weeks. The Sox2(+) stem/progenitor cell compartment displays a prompt reaction to
      the DT-triggered cell ablation injury, including expansion of the marginal-zone
      niche and coexpression of PRL, the latter only very rarely observed in control
      pituitary. Throughout the regeneration period (2-6 weeks), Sox2(+) as well as
      double Sox2(+)/PRL(+) cells continue to be more abundant than in control
      pituitary. In addition to this stem cell reaction, surviving or newborn
      lactotropes increase their proliferative activity, and bihormonal PRL(+)/GH(+)
      cells become detectable suggesting somatotrope-to-lactotrope
      transdifferentiation. In conclusion, the adult pituitary gland is capable of
      restoring lactotrope cells after destruction, further confirming its regenerative
      competence. Repair of lactotropes appears to be driven by a combination of
      mechanisms, including recruitment from stem cells, proliferation of lactotropes,
      and transdifferentiation of somatotropes.

PMID- 22970886
TI  - Antimicrobial efficacy of a high-power diode laser, photo-activated disinfection,
      conventional and sonic activated irrigation during root canal treatment.
AB  - AIM: To evaluate the antimicrobial effect of a diode laser irradiation, photo
      activated disinfection (PAD), conventional and sonic activated irrigation with
      2.5% sodium hypochlorite (NaOCl) on Enterococcus faecalis. METHODOLOGY: Root
      canals of 120 human extracted teeth with single straight canals were prepared
      with ProTaper files, sterilized, contaminated with an E. faecalis suspension and
      incubated for 7 days. They were then randomly distributed into six groups: G1,
      diode laser irradiation (2 W, 3 * 20 s); G2, PAD (100 mW, 60 s); G3, PAD with 3D
      Endoprobe (100 mW, 60 s); G4, 30-gauge syringe irrigation with NaOCl (60 s); G5,
      sonic agitation of NaOCl with the EndoActivator system (60 s); G6, 30-gauge
      syringe irrigation with NaCl (60 s). The pattern of colonization was visualized
      by scanning electron microscopy. The root canals were sampled by flushing with
      saline solution at baseline and after the treatments. The number of bacteria in
      each canal was determined by plate count. The presence and the absence of E.
      faecalis in root canals were also demonstrated by polymerase chain reaction
      (PCR). RESULTS: There was a significant reduction in the bacterial population
      after all treatments (P < 0.001). The PAD, using both laser systems, and the
      sonic activated NaOCl irrigation were significantly more effective than diode
      irradiation and single NaOCl irrigation in reducing CFUs (P < 0.05). High-power
      diode laser and single NaOCl irrigation had an equal antibacterial effect (P >
      0.05). CONCLUSIONS: The PAD and EndoActivator system were more successful in
      reducing the root canal infection than the diode laser and NaOCl syringe
      irrigation alone.

PMID- 22970890
TI  - Standard operating procedure for the preservation of erectile function outcomes
      after radical prostatectomy.
AB  - INTRODUCTION: Prostate cancer is common, and, thus, more men are being treated
      surgically. Long-term functional outcomes are of significant importance to the
      patient and their partners. Erectile function (EF) preservation (rehabilitation)
      has gained significant traction worldwide, despite the absence of definitive
      evidence supporting its use. AIM: To review the effectiveness of specific
      pharmacological therapies and other erectogenic aids in the treatment of post
      radical prostatectomy (RP) erectile dysfunction. METHODS: A systematic literature
      review of original peer-reviewed manuscripts and clinical trials reported in
      Medline. MAIN OUTCOME MEASURE: This review focused on the evaluation of
      interventions that aimed to improve EF recovery following RP. RESULTS: Although
      well documented in animal models, studies supporting the rehabilitation with
      phosphodiesterase type 5 inhibitors in humans are scarce. Daily sildenafil has
      been used in trials (only one randomized placebo-controlled trial) with a
      significant improvement in erection recovery when compared to placebo or no
      rehabilitation but with a low return to baseline rates (27% vs. 4% placebo).
      Nightly vardenafil vs. on demand vs. placebo has been studied in the Recovery of
      Erections: INtervention with Vardenafil Early Nightly Therapy trial with no
      difference in erection recovery following RP. Intracavernosal injections,
      although widely used and attractive from a rehabilitation standpoint, does not
      yet have definitive supporting its role in rehabilitation. Vacuum erection
      devices use following RP has been reported, but there are no data to support its
      role as monotherapy. Intraurethral alprostadil was also studied vs. sildenafil in
      a multicenter, randomized, open-label trial, and no superiority was found.
      CONCLUSIONS: At this time, we are unable to define what represents the optimal
      rehabilitation program in regard to strategies utilized, timing of intervention,
      or duration of treatment.

PMID- 22970889
TI  - Statistical adjustment of genotyping error in a case-control study of childhood
      leukaemia.
AB  - BACKGROUND: Genotyping has become more cost-effective and less invasive with the
      use of buccal cell sampling. However, low or fragmented DNA yields from buccal
      cells collected using FTA cards often requires additional whole genome
      amplification to produce sufficient DNA for genotyping. In our case-control study
      of childhood leukaemia, discordance was found between genotypes derived from
      blood and whole genome amplified FTA buccal DNA samples. We aimed to develop a
      user-friendly method to correct for this genotype misclassification, as existing
      methods were not suitable for use in our study. METHODS: Discordance between the
      results of blood and buccal-derived DNA was assessed in childhood leukaemia cases
      who had both blood and FTA buccal samples. A method based on applying
      misclassification probabilities to measured data and combining results using
      multiple imputations, was devised to correct for error in the genotypes of
      control subjects, for whom only buccal samples were available, to minimize bias
      in the odds ratios in the case-control analysis. RESULTS: Application of the
      correction method to synthetic datasets showed it was effective in producing
      correct odds ratios from data with known misclassification. Moreover, when
      applied to each of six bi-allelic loci, correction altered the odds ratios in the
      logically anticipated manner given the degree and direction of the
      misclassification revealed by the investigations in cases. The precision of the
      effect estimates decreased with decreasing size of the misclassification data
      set. CONCLUSIONS: Bias arising from differential genotype misclassification can
      be reduced by correcting results using this method whenever data on concordance
      of genotyping results with those from a different and probably better DNA source
      are available.

PMID- 22970887
TI  - The association between DRD2/ANKK1 and genetically informed measures of alcohol
      use and problems.
AB  - In 1990, Blum and colleagues first reported an association between DRD2 and
      alcoholism. While there have been subsequent replications of this genetic
      association, there have also been numerous studies that failed to detect an
      association between DRD2 and alcohol dependence. We propose that one aspect
      contributing to this inconsistency is the variation in alcohol phenotype used
      across studies. Within the population-based Finnish twin sample, FinnTwin16, we
      previously performed multivariate twin analyses to extract latent genetic
      factors, which account for the variation across seven measures of alcohol
      consumption (frequency of drinking, frequency * quantity, frequency of heavy
      drinking, frequency of intoxication and maximum drinks in a 24-hour period) and
      problems (the Rutgers Alcohol Problem Index-RAPI and the Malmo-modified Michigan
      Alcohol Screen Test-MmMAST) in 3065 twins. In the present study, we examined the
      association between 31 DRD2/ANKK1 single-nucleotide polymorphisms (SNPs) and the
      genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n =
      602). We focus on two of the genetic factors: a general alcohol consumption and
      problems factor score, which represents shared genetic variance across alcohol
      measures, and a alcohol problems genetic factor score, which loads onto the two
      indices of problematic drinking (MAST and RAPI). After correction for multiple
      testing across SNPs and phenotypes, of the 31 SNPs genotyped across DRD2/ANKK1,
      one SNP (rs10891549) showed significant association with the general alcohol
      consumption and problems factor score (P = 0.004), and four SNPs (rs10891549,
      rs1554929, rs6275, rs6279), representing two independent signals after accounting
      for linkage disequilibrium, showed significant association with the alcohol
      problems genetic factor score (P = 0.005, P = 0.005, P = 0.003, P = 0.003). In
      this study, we provide additional positive evidence for the association between
      DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking
      problems. Additionally, post hoc analyses indicate stronger association signals
      using genetic factor scores than individual measures, which suggest that
      accounting for the genetic architecture of the alcohol measures reduces genetic
      heterogeneity in alcohol dependence outcomes in this sample and enhances the
      ability to detect association.

PMID- 22970891
TI  - Mortality due to pulmonary embolism, myocardial infarction, and stroke among
      incident dialysis patients.
AB  - BACKGROUND: It is has been suggested that dialysis patients have lower mortality
      rates for pulmonary embolism than the general population, because of platelet
      dysfunction and bleeding tendency. However, there is limited information whether
      dialysis is indeed associated with a decreased mortality risk from pulmonary
      embolism. OBJECTIVE: The aim of our study was to evaluate whether mortality rate
      ratios for pulmonary embolism were lower than for myocardial infarction and
      stroke in dialysis patients compared with the general population. METHODS:
      Cardiovascular causes of death for 130,439 incident dialysis patients registered
      in the ERA-EDTA Registry were compared with the cardiovascular causes of death
      for the European general population. RESULTS: The age- and sex-standardized
      mortality rate (SMR) from pulmonary embolism was 12.2 (95% CI 10.2-14.6) times
      higher in dialysis patients than in the general population. The SMRs in dialysis
      patients compared with the general population were 11.0 (95% CI 10.6-11.4) for
      myocardial infarction, 8.4 (95% CI 8.0-8.8) for stroke, and 8.3 (95% CI 8.0-8.5)
      for other cardiovascular diseases. In dialysis patients, primary kidney disease
      due to diabetes was associated with an increased mortality risk due to pulmonary
      embolism (HR 1.9; 95% CI 1.0-3.8), myocardial infarction (HR 4.1; 95% CI 3.4
      4.9), stroke (HR 3.5; 95% CI 2.8-4.4), and other cardiovascular causes of death
      (HR 3.4; 95% CI 2.9-3.9) compared with patients with polycystic kidney disease.
      CONCLUSIONS: Dialysis patients were found to have an unexpected highly increased
      mortality rate for pulmonary embolism and increased mortality rates for
      myocardial infarction and stroke.

PMID- 22970888
TI  - The FAAH inhibitor URB597 efficiently reduces tyrosine hydroxylase expression
      through CB1- and FAAH-independent mechanisms.
AB  - BACKGROUND: Anandamide and 2-arachidonoylglycerol are neuromodulatory lipids
      interacting with cannabinoid receptors, whose availability is regulated by the
      balance between 'on demand' generation and enzymatic degradation [by fatty acid
      amide hydrolase (FAAH)/monoacylglycerol lipase]. Given the reported effects of
      anandamide on dopamine transmission, we investigated the influence of
      endocannabinoids and URB597, a well-known FAAH inhibitor, on the expression of
      tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis.
      EXPERIMENTAL APPROACH: We investigated TH expression in N1E115 neuroblastoma
      using a reporter gene assay, as well as mRNA and protein quantifications. FAAH
      inhibition was confirmed by measuring radiolabelled substrate hydrolysis and
      endogenous endocannabinoids. KEY RESULTS: Anandamide decreased TH promoter
      activity in N1E115 cells through CB1 receptor activation. Unexpectedly, URB597
      reduced TH expression (pEC50 = 8.7 +/- 0.2) through FAAH-independent mechanisms.
      Indeed, four structurally unrelated inhibitors of FAAH had no influence on TH
      expression, although all the inhibitors increased endocannabinoid levels. At
      variance with the endocannabinoid responses, the use of selective antagonists
      indicated that the URB597-mediated decrease in TH expression was not directed by
      the CB1 receptor, but rather by abnormal-cannabidiol-sensitive receptors and
      PPARs. Further supporting the physiological relevance of these in vitro data,
      URB597 administration resulted in reduced TH mRNA levels in mice brain.
      CONCLUSIONS: While confirming the implication of endocannabinoids on the
      modulation of TH, we provide strong evidence for additional physiologically
      relevant off-target effects of URB597. In light of the numerous preclinical
      studies involving URB597, particularly in anxiety and depression, the existence
      of non-CB1 and non-FAAH mediated influences of URB597 on key enzymes of the
      catecholaminergic transmission system should be taken into account when
      interpreting the data.

PMID- 22970892
TI  - Factors affecting levels of urinary albumin excretion in the general population
      of Spain: the Di@bet.es study.
AB  - The present study was undertaken to examine the prevalence of urinary ACR
      (albumin/creatinine ratio) >30 mg/g and the associated clinical and environmental
      factors in a representative sample of the population of Spain. Di@bet.es study is
      a national, cross-sectional population-based survey conducted in 2009-2010.
      Clinical, metabolic, socio-demographic, anthropometric data and information about
      lifestyle habit were collected. Those subjects without KDM (known diabetes
      mellitus) were given an OGTT (oral glucose tolerance test). Albumin and
      creatinine were measured in a urinary sample and ACR was calculated. The
      population prevalence of ACR >30 mg/g was 7.65% (adjusted for sex and age). The
      prevalence of ACR >30 mg/g increased with age (P<0.001). Subjects with
      carbohydrate metabolism disorders had a greater prevalence of ACR >30 mg/g but
      after being adjusted for age, sex and hypertension, was significant only in those
      subjects with UKDM (unknown diabetes mellitus) {OR (odd ratio), 2.07 [95% CI
      (confidence interval), 1.38-3.09]; P<0.001] and KDM [OR, 3.55 (95% CI, 2.63
      4.80); P<0.001]. Prevalence of ACR >30 mg/g was associated with hypertension [OR,
      1.48 (95% CI, 1.12-1.95); P=0.001], HOMA-IR (homoeostasis model assessment of
      insulin resistance) [OR, 1.47 (95% CI, 1.13-1.92); P<=0.01], metabolic syndrome
      [OR, 2.17 (95% CI, 1.72-2.72); P<0.001], smoking [OR, 1.40 (95% CI, 1.06-1.83);
      P<=0.05], physical activity [OR, 0.68 (95% CI, 0.54-0.88); P<=0.01] and
      consumption of fish [OR, 0.38 (95% CI, 0.18-0.78); P<=0.01]. This is the first
      study that reports the prevalence of ACR >30 mg/g in the Spanish population. The
      association between clinical variables and other potentially modifiable
      environmental variables contribute jointly, and sometimes interactively, to the
      explanation of prevalence of ACR >30 mg/g. Many of these risk factors are
      susceptible to intervention.

PMID- 22970893
TI  - Racial/ethnic disparities in provision of dental procedures to children enrolled
      in Delta Dental insurance in Milwaukee, Wisconsin.
AB  - OBJECTIVES: Most studies on the provision of dental procedures have focused on
      Medicaid enrollees known to have inadequate access to dental care. Little
      information on private insurance enrollees exists. This study documents the rates
      of preventive, restorative, endodontic, and surgical dental procedures provided
      to children enrolled in Delta Dental of Wisconsin (DDWI) in Milwaukee. METHODS:
      We analyzed DDWI claims data for Milwaukee children aged 0-18 years between 2002
      and 2008. We linked the ZIP codes of enrollees to the 2000 U.S. Census
      information to derive racial/ethnic estimates in the different ZIP codes. We
      estimated the rates of preventive, restorative, endodontic, and surgical
      procedures provided to children in different racial/ethnic groups based on the
      population estimates derived from the U.S. Census data. Descriptive and
      multivariable analysis was done using Poisson regression modeling on dental
      procedures per year. RESULTS: In 7 years, a total of 266,380 enrollees were
      covered in 46 ZIP codes in the database. Approximately, 64 percent, 44 percent,
      and 49 percent of White, African American, and Hispanic children had at least one
      dental visit during the study period, respectively. The rates of preventive
      procedures increased up to the age of 9 years and decreased thereafter among
      children in all three racial groups included in the analysis. African American
      and Hispanic children received half as many preventive procedures as White
      children. CONCLUSION: Our study shows that substantial racial disparities may
      exist in the types of dental procedures that were received by children.

PMID- 22970894
TI  - GRID-based three-dimensional pharmacophores I: FLAPpharm, a novel approach for
      pharmacophore elucidation.
AB  - Pharmacophore elucidation approaches are routinely used in drug discovery,
      primarily with the aim of determining the three-dimensional arrangement of common
      features shared by ligands interacting at the site of interest; these features
      can then be used to investigate the structure-activity relationship between the
      ligands and also to screen for other molecules possessing the relevant features.
      Here we present a novel approach based on GRID molecular interaction fields and
      the derivative method FLAP that has been previously described, which provides a
      common reference framework to compare both small molecule ligands and
      macromolecular protein targets. Unlike classical pharmacophore elucidation
      approaches that extract simplistic molecular features, determine those which are
      common across the data set, and use these features to align the structures,
      FLAPpharm first aligns the structures and subsequently extracts the common
      interacting features in terms of their molecular interaction fields,
      pseudofields, and atomic points, representing the common pharmacophore as a more
      comprehensive pharmacophoric pseudomolecule. The approach is applied to a number
      of data sets to investigate performance in terms of reproducing the X-ray
      crystallography-based alignment, in terms of its discriminatory ability when
      applied to virtual screening and also to illustrate its ability to explain
      alternative binding modes. In part two of this publication, a comprehensive
      benchmark data set for pharmacophore elucidation is presented and the performance
      of FLAPpharm discussed.

PMID- 22970895
TI  - Transforming anion instability into stability: contrasting photoionization of
      three protonation forms of the phosphate ion upon moving into water.
AB  - We use photoelectron emission spectroscopy with vacuum microjet technique and
      quantum chemistry calculations to investigate electronic structure and stability
      of aqueous phosphate anions. On the basis of the measured photoelectron spectra
      of sodium phosphates at different pH, we report the lowest vertical ionization
      energies of monobasic (9.5 eV), dibasic (8.9 eV), and tribasic (8.4 eV) anions.
      Electron binding energies were in tandem modeled with ab initio methods, using a
      mixed dielectric solvation model together with up to 64 explicitly solvating
      water molecules. We demonstrate that two solvation layers of explicit water
      molecules are needed to obtain converged values of vertical ionization energies
      (VIEs) within this mixed solvation model, leading to very good agreement with
      experiment. We also show that the highly charged PO(4)(3-) anion, which is
      electronically unstable in the gas phase, gains the electronic stability with
      about 16 water molecules, while only 2-3 water molecules are sufficient to
      stabilize the doubly charged phosphate anion. We also investigate the effect of
      ion pairing on the vertical ionization energy. In contrast to protonation
      (leading to a formation of covalent O-H bond), sodiation (leading to an
      anion...Na(+) ion pair) has only a weak effect on the electron binding energy.

PMID- 22970896
TI  - Extracorporeal shock wave lithotripsy for distal ureteral calculi: improved
      efficacy using low frequency.
AB  - OBJECTIVES: To compare low versus high frequency for lithotripsy in the
      management of distal ureteral calculi. METHODS: A total of 154 patients with
      radio-opaque calculi (0.5-1 cm diameter) in the distal ureter were randomized to
      be given either lithotripsy at 80 or 60 pulses per min (high frequency or low
      frequency groups, respectively). The number of waves and sessions received, and
      time to total resolution were measured. A Dornier Compact Delta lithotripter was
      used. RESULTS: A total of 72 patients were assigned to the high frequency group
      and 78 to the low frequency group. Four patients were excluded from the study
      because of intolerance of the procedure. The size was slightly lower in low
      frequency group, whereby an analysis of covariance was carried out to eliminate
      the size factor, with the limit established as 0.7 cm. The low frequency group
      received 2980 +/- 1211 waves, and the high frequency group received 5752 +/- 3121
      (P<0.001). The success rate was higher in the low frequency group (100%) than in
      the high frequency group (92.9%; P=0.02). If adjusted to the size of the calculus
      with a threshold of 0.7 cm, there was a difference, although it was not
      statistically significant. The time to elimination of the fragments was higher in
      the high frequency group (17.68 days) than in the low frequency group (7.15 days;
      P<0.001). The number of sessions necessary for resolution was higher in the high
      frequency group (1.56) than in the low frequency group (1.14; P<0.001).
      CONCLUSIONS: Lithotripsy at 60 pulses provides better outcomes than lithotripsy
      at 80 pulses for the treatment of distal ureteral calculi.

PMID- 22970897
TI  - Accuracy and precision of compounded ciclosporin capsules and solution.
AB  - BACKGROUND: The prescribing of compounded products that mimic US Federal Drug
      Administration approved drugs in the USA is inappropriate. Among the reasons are
      the lack of premarket regulatory assessment and the potential for an inferior
      product. This study describes the accuracy and precision of ciclosporin (CsA)
      strength when compounded as capsules (10 and 300 mg) and solutions (50 and 150
      mg/mL). METHODS: Preparation choices reflected current prescribing practices.
      Each was acquired by prescription from five pharmacies at three different times,
      14-45 days apart. Atopica((r)) (10 and 100 mg; Novartis, Greensboro, NC, USA) and
      three human generics (50 and 100 mg capsules and 100 mg/mL solution) were
      positive controls. Physical characteristics were assessed. Accuracy (percentage
      predicted) was based on CsA strength measured by high-performance liquid
      chromatography and precision was based on replications (n = 3) from each
      pharmacy. RESULTS: Accuracy of positive controls ranged from 92 to 103%. For
      compounded solutions, physical characteristics differed markedly between but not
      within pharmacies. Capsule accuracy was 10 +/- 0.98 mg (101%) for 10 mg and 290
      +/- 9.6 mg (97%) for 300 mg; and solution accuracy was 45 +/- 9.9 mg/mL (90%) for
      50 mg/mL and 127 +/- 18 mg/mL (85%) for 150 mg/mL. The precision for 50 mg/mL
      oral solution was 0.67-11%, and for 150 mg/mL, 3.7-14%. Accuracy for all
      preparations varied, with the least accurate deviating by 34% from labelled
      strength. Precision for all capsules ranged from 0.6 to 8.7%. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Compounded CsA solutions may deviate by more than 10% from
      the labelled strength. Bioavailability and clinical efficacy of compounded CsA
      remain unknown, and such products should be prescribed only in appropriate
      circumstances.

PMID- 22970898
TI  - Cue reactivity and its inhibition in pathological computer game players.
AB  - Despite a rising social relevance of pathological computer game playing, it
      remains unclear whether the neurobiological basis of this addiction-like
      behavioral disorder and substance-related addiction are comparable. In substance
      related addiction, attentional bias and cue reactivity are often observed. We
      conducted a functional magnetic resonance study using a dot probe paradigm with
      short-presentation (attentional bias) and long-presentation (cue reactivity)
      trials in eight male pathological computer game players (PCGPs) and nine healthy
      controls (HCs). Computer game-related and neutral computer-generated pictures, as
      well as pictures from the International Affective Picture System with positive
      and neutral valence, served as stimuli. PCGPs showed an attentional bias toward
      both game-related and affective stimuli with positive valence. In contrast, HCs
      showed no attentional bias effect at all. PCGPs showed stronger brain responses
      in short-presentation trials compared with HCs in medial prefrontal cortex (MPFC)
      and anterior cingulate gyrus and in long-presentation trials in lingual gyrus. In
      an exploratory post hoc functional connectivity analyses, for long-presentation
      trials, connectivity strength was higher between right inferior frontal gyrus,
      which was associated with inhibition processing in previous studies, and cue
      reactivity-related regions (left orbitofrontal cortex and ventral striatum) in
      PCGPs. We observed behavioral and neural effects in PCGPs, which are comparable
      with those found in substance-related addiction. However, cue-related brain
      responses were depending on duration of cue presentation. Together with the
      connectivity result, these findings suggest that top-down inhibitory processes
      might suppress the cue reactivity-related neural activity in long-presentation
      trials.

PMID- 22970899
TI  - The effect of nonsetting calcium hydroxide on root fracture and mechanical
      properties of radicular dentine: a systematic review.
AB  - The aim of this review was to identify and analyse all studies related to the
      effect of nonsetting calcium hydroxide [Ca(OH)(2)] on root fracture and various
      mechanical properties of radicular dentine. A PubMed search was conducted using
      the keywords 'calcium hydroxide' and 'dentistry' combined with MeSH terms 'tooth
      fractures' or 'mechanical phenomena' or 'compressive strength'. The search was
      expanded by including Embase and Web of Science databases, using the keywords
      'calcium hydroxide' and 'root' and 'fracture'. The search was supplemented by
      checking the reference lists from each selected article. Each study had to meet
      the following criteria to be selected for review: (i) Inclusion of at least one
      experimental group with root or radicular dentine either filled with or exposed
      to nonsetting Ca(OH)(2); (ii) inclusion of at least one appropriate control
      group; and (iii) a minimum of five samples per experimental group. Only articles
      written in English were included. Of the 16 studies selected initially, 12 in
      vitro studies fulfilled the selection criteria for inclusion in the final review.
      No clinical studies that directly supported the correlation between Ca(OH)(2)
      intracanal dressing and root fracture were found in the literature. However, the
      majority of in vitro studies showed reduction in the mechanical properties of
      radicular dentine after exposure to Ca(OH)(2) for 5 weeks or longer. Conversely,
      the data were inconclusive regarding whether Ca(OH)(2) exposure for 1 month or
      less had a negative effect on the mechanical properties of radicular dentine.

PMID- 22970900
TI  - An examination of racial/ethnic disparities in children's oral health in the
      United States.
AB  - OBJECTIVE: To assess the extent factors other than race/ethnicity explain
      apparent racial/ethnic disparities in children's oral health and oral health
      care. METHODS: Data were from the 2007 National Survey of Children's Health, for
      children 2-17 years (n=82,020). Outcomes included parental reports of child's
      oral health status, receiving preventive dental care, and delayed dental
      care/unmet need. Model-based survey-data-analysis examined racial/ethnic
      disparities, controlling for child, family, and community/state (contextual)
      factors. RESULTS: Unadjusted results show large racial/ethnic oral health
      disparities. Compared with non-Hispanic White people, Hispanic and non-Hispanic
      Black people were markedly more likely to be reported in only fair/poor oral
      health [odds ratios (ORs) (95% confidence intervals) 4.3 (4.0-4.6), 2.2 (2.0
      2.4), respectively], lack preventive care [ORs 1.9 (1.8-2.0), 1.4 (1.3-1.5)], and
      experience delayed care/unmet need [ORs 1.5 (1.3-1.7), 1.4 (1.3-1.5)]. Adjusting
      for child, family, and community/state factors reduced racial/ethnic disparities.
      Adjusted ORs (AORs) for Hispanics and non-Hispanic Blacks attenuated for
      fair/poor oral health, to 1.6 (1.5-1.8) and 1.2 (1.1-1.4), respectively.
      Adjustment eliminated disparities for lacking preventive care [AORs 1.0 (0.9
      1.1), 1.1 (1.1-1.2)] and in Hispanics for delayed care/unmet need (AOR 1.0).
      Among non-Hispanic Blacks, adjustment reversed the disparity for delayed
      care/unmet need [AOR 0.6 (0.6-0.7)]. CONCLUSIONS: Racial/ethnic disparities in
      children's oral health status and access were attributable largely to
      socioeconomic and health insurance factors. Efforts to decrease disparities may
      be more efficacious if targeted at social, economic, and other factors associated
      with minority racial/ethnic status and may have positive effects on all who share
      similar social, economic, and cultural characteristics.

PMID- 22970901
TI  - Molecular mechanism for the preferential exclusion of TMAO from protein surfaces.
AB  - Trimethylamine N-oxide (TMAO) is a naturally occurring protecting osmolyte that
      stabilizes the folded state of proteins and also counteracts the destabilizing
      effect of urea on protein stability. Experimentally, it has been inferred that
      TMAO is preferentially excluded from the vicinity of protein surfaces. Here, we
      combine computer modeling and experimental measurements to gain an understanding
      of the mechanism of the protecting effect of TMAO on proteins. We have developed
      an all-atom molecular model for TMAO that captures the exclusion of TMAO from
      model compounds and protein surfaces, as a consequence of incorporating realistic
      TMAO-water interactions through osmotic pressure measurements. Osmotic pressure
      measurements also suggest no significant attraction between urea and TMAO
      molecules in solution. To obtain an accurate potential for molecular simulations
      of protein stability in TMAO solutions, we have explored different ways of
      parametrizing the protein/osmolyte and osmolyte/osmolyte interactions by scaling
      charges and the strength of Lennard-Jones interactions and carried out
      equilibrium folding experiments of Trp-cage miniprotein in the presence of TMAO
      to guide the parametrization. Our calculations suggest a general principle for
      preferential interaction behavior of cosolvents with protein surfaces-
      preferentially excluded osmolytes have repulsive self-interaction given by
      osmotic coefficient phi > 1, while denaturants, in addition to having attractive
      interactions with the proteins, have favorable self-interaction given by osmotic
      coefficient phi < 1, to enable preferential accumulation in the vicinity of
      proteins.

PMID- 22970902
TI  - Visual contrast sensitivity in patients with impairment of functional
      independence after stroke.
AB  - BACKGROUND: Stroke has been considered a serious public health problem in many
      countries, accounting for complex disorders involving perception, such as visual,
      cognitive and functional deficits. The impact of stroke on the visual perception
      of individuals with impairments in functional independence was investigated.
      METHODS: We measured changes in functional independence and visual function in 40
      patients with stroke (M = 52.3, SD = 0.65) and 10 controls (M = 52.5, SD = 0.66).
      The patients were divided into four subgroups following the Barthel Index (Group
      A: 20-35, serious dependence; Group B: 40-55, moderate dependence; Group C: 60
      95, mild dependence; and Group D: 100 points, independence). Visual function was
      evaluated using the Contrast Sensitivity Function (CSF). The contrast threshold
      was measured using a temporal, two-alternative, forced-choice psychophysical
      method. RESULTS: The results show significant differences in CSF between healthy
      volunteers and patients with stroke (F (1.56) = 151.2, p < 0.001) for all
      frequencies (F (2.56) = 125.96, p < 0.001). The results also show that patients
      with low functional independence had lower contrast sensitivity than those with
      greater functional independence (F (3.56) = 344.82, p < 0.001). CONCLUSIONS: An
      association exists between CSF and a worsening in the functional potential for
      performing daily living activities. Our results suggest that the CSF can be used
      as a diagnostic tool to analyze visual function associated with deficits in
      functional independence after stroke. These findings should be considered across
      the continuum of care for these patients.

PMID- 22970903
TI  - Imported submicroscopic malaria in Madrid.
AB  - BACKGROUND: Submicroscopic malaria (SMM) can be defined as low-density infections
      of Plasmodium that are unlikely to be detected by conventional microscopy. Such
      submicroscopic infections only occasionally cause acute disease, but they are
      capable of infecting mosquitoes and contributing to transmission. This entity is
      frequent in endemic countries; however, little is known about imported SMM.The
      goals of this study were two-fold: a) to know the frequency of imported SMM, and
      b) to describe epidemiological, laboratorial and clinical features of imported
      SMM. METHODS: A retrospective study based on review of medical records was
      performed. The study population consisted of patients older than 15 years
      attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1,
      2002 and December 31, 2007. Routinely detection techniques for Plasmodium
      included Field staining and microscopic examination through thick and thin blood
      smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm
      cases with low parasitaemia. RESULTS: SMM was diagnosed in 104 cases,
      representing 35.5% of all malaria cases. Mean age (IC95%) was 40.38 years (37.41
      43.34), and sex distribution was similar. Most cases were in immigrants, but some
      cases were found in travellers. Equatorial Guinea was the main country where
      infection was acquired (81.7%). Symptoms were present only in 28.8% of all SMM
      cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and
      arthromialgias (53.3%). The associated laboratory abnormalities were anaemia
      (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%). Co-morbidity was
      described in 75 cases (72.1%). CONCLUSIONS: Results from this study suggest that
      imported SMM should be considered in some patients attended at Tropical Medicine
      Units. Although it is usually asymptomatic, it may be responsible of fever, or
      laboratory abnormalities in patients coming from endemic areas. The possibility
      of transmission in SMM has been previously described in endemic zones, and
      presence of vector in Europe has also been reported. Implementation of molecular
      tests in all asymptomatic individuals coming from endemic area is not
      economically feasible. So re-emergence of malaria (Plasmodium vivax) in Europe
      may be speculated.

PMID- 22970904
TI  - Icatibant , the bradykinin B2 receptor antagonist with target to the
      interconnected kinin systems.
AB  - INTRODUCTION: HOE-140/ Icatibant is a selective, competitive antagonist to
      bradykinin (BK) against its binding to the kinin B2 receptor. Substitution of
      five non-proteogeneic amino acid analogues makes icatibant resistant to
      degradation by metalloproteases of kinin catabolism. Icatibant has clinical
      applications in inflammatory and vascular leakage conditions caused by an acute
      (non-controlled) production of kinins and their accumulation at the endothelium
      B2 receptor. The clinical manifestation of vascular leakage, called angioedema
      (AE), is characterized by edematous attacks of subcutaneous and submucosal
      tissues, which can cause painful intestinal consequences, and life-threatening
      complications if affecting the larynx. Icatibant is registered for the treatment
      of acute attacks of the hereditary BK-mediated AE, i.e., AE due to C1 inhibitor
      deficiency. AREAS COVERED: This review discusses emerging knowledge on the kinin
      system: kinin pharmacological properties, biochemical characteristics of the
      contact phase and kinin catabolism proteases. It underlines the responsibility of
      the kinins in AE initiation and the potency of icatibant to inhibit AE formation
      by kinin-receptor interactions. EXPERT OPINION: Icatibant antagonist properties
      protect BK-mediated AE patients against severe attacks, and could be developed
      for use in inflammatory conditions. More studies are required to confirm whether
      or not prolonged and frequent applications of icatibant could result in the
      impairment of the cardioprotective effect of BK.

PMID- 22970905
TI  - Reactivity of U-E-U (E = S, Se) toward CO2, CS2, and COS: new mixed-carbonate
      complexes of the types U-CO2E-U (E = S, Se), U-CS2E-U (E = O, Se), and U-COSSe-U.
AB  - We recently reported the formation of a bridging carbonate complex
      [{(((Ad)ArO)(3)N)U}(2)(MU-eta(1):kappa(2)-CO(3))] via reductive cleavage of
      CO(2), yielding a MU-oxo bridged complex, followed by the insertion of another
      molecule of CO(2). In a similar strategy, we were able to isolate and
      characterize a series of mixed carbonate complexes U-CO(2)E-U, U-CS(2)E-U, and
      even U-OC(S)Se-U, by reacting bridged chalcogenide complexes
      [{(((Ad)ArO)(3)N)U}(2)(MU-E)] (E = S, Se) with CO(2), CS(2), and COS. These
      chalcogenido mixed-carbonate complexes represent the first of their kind.

PMID- 22970906
TI  - NF-kappaB1 deficiency stimulates the progression of non-alcoholic steatohepatitis
      (NASH) in mice by promoting NKT-cell-mediated responses.
AB  - Growing evidence indicates that NF-kappaB (nuclear factor kappaB) activation
      contributes to the pathogenesis of NASH (non-alcoholic steatohepatisis). Among
      the NF-kappaB subunits, p50/NF-kappaB1 has regulatory activities down-modulating
      NF-kappaB-mediated responses. In the present study, we investigated the effects
      of NF-kappaB1 deficiency on the progression of NASH induced by feeding mice on an
      MCD (methionine/choline-deficient) diet. Following 4 weeks on the MCD diet,
      steatosis, ALT (alanine aminotransferase) release, hepatocyte apoptosis, lobular
      inflammation and TNFalpha (tumour necrosis factor alpha) production were higher
      in NF-kappaB1(-/-) (NF-kappaB1-knockout) mice than in WT (wild-type) mice. NF
      kappaB1(-/-) mice also showed appreciable centrilobular collagen deposition, an
      increased number of activated hepatic stellate cells and higher type-I
      procollagen-alpha and TIMP-1 (tissue inhibitor of metalloproteases-1) mRNA
      expression. Although NF-kappaB p50 homodimers regulate macrophage activation, the
      number of hepatic macrophages and liver mRNAs for iNOS (inducible NO synthase),
      IL (interleukin)-12p40, CCL2 (CC chemokine ligand 2) and CXCL10 (CXC chemokine
      ligand 10) were comparable in the two strains. NASH was associated with an
      increase in liver infiltrating T-cells that was more evident in MCD-fed NF
      kappaB1(-/-) than in similarly treated WT mice. Flow cytorimetry showed that T
      cell recruitment involved effector CD8+ T-cells without changes in the helper
      CD4+ T-cell fraction. Furthermore, although NASH lowered hepatic NKT cells [NK
      (natural killer) T-cells] in WT mice, the NKT cell pool was selectively increased
      in the livers of MCD-fed NF-kappaB1(-/-) mice. Such NKT cell recruitment was
      associated with an early overexpression of IL-15, a cytokine controlling NKT cell
      survival and maturation. In the livers of MCD-fed NF-kappaB1(-/-) mice, but not
      in those of WT littermates, we also observed an up-regulation in the production
      of NKT-related cytokines IFN (interferon)-gamma and osteopontin. Taken together,
      these results indicate that NF-kappaB1 down-modulation enhanced NASH progression
      to fibrosis by favouring NKT cell recruitment, stressing the contribution of NKT
      cells in the pathogenesis of NASH.

PMID- 22970907
TI  - Challenges enrolling patients with acute ischemic stroke into cell therapy
      trials.
AB  - Infusion of autologous bone marrow-derived mononuclear cells (MNCs) is a
      promising investigational therapeutic approach for patients with acute ischemic
      stroke. Preclinical models indicate that MNCs can reduce neurological deficits
      and enhance recovery. We recently concluded a phase I clinical trial to determine
      the safety and feasibility of these cells in patients with acute ischemic stroke.
      In this article, we discuss practical barriers and challenges encountered during
      the trial and provide lessons learned for the design and planning of future
      clinical trials testing novel cell therapies for acute ischemic stroke.

PMID- 22970908
TI  - Uptake and transfection with polymeric nanoparticles are dependent on polymer end
      group structure, but largely independent of nanoparticle physical and chemical
      properties.
AB  - Development of nonviral particles for gene delivery requires a greater
      understanding of the properties that enable gene delivery particles to overcome
      the numerous barriers to intracellular DNA delivery. Linear poly(beta-amino)
      esters (PBAE) have shown substantial promise for gene delivery, but the mechanism
      behind their effectiveness is not well quantified with respect to these barriers.
      In this study, we synthesized, characterized, and evaluated for gene delivery an
      array of linear PBAEs that differed by small changes along the backbone, side
      chain, and end group of the polymers. We examined particle size and surface
      charge, polymer molecular weight, polymer degradation rate, buffering capacity,
      cellular uptake, transfection, and cytotoxicity of nanoparticles formulated with
      these polymers. Significantly, this is the first study that has quantified how
      small differential structural changes to polymers of this class modulate
      buffering capacity and polymer degradation rate and relates these findings to
      gene delivery efficacy. All polymers formed positively charged (zeta potential 21
      29 mV) nanosized particles (~150 nm). The polymers hydrolytically degraded
      quickly in physiological conditions, with half-lives ranging from 90 min to 6 h
      depending on polymer structure. The PBAE buffering capacities in the relevant pH
      range (pH 5.1-7.4) varied from 34% to 95% protonatable amines, and on a per mass
      basis, PBAEs buffered 1.4-4.6 mmol of H(+)/g. When compared to 25 kDa branched
      polyethyleneimine (PEI), PBAEs buffer significantly fewer protons/mass, as PEI
      buffers 6.2 mmol of H(+)/g over the same range. However, due to the relatively
      low cytotoxicity of PBAEs, higher polymer mass can be used to form particles than
      with PEI and total buffering capacity of PBAE-based particles significantly
      exceeds that of PEI. Uptake into COS-7 cells ranged from 0% to 95% of cells and
      transfection ranged from 0% to 93% of cells, depending on the base polymer
      structure and the end modifications examined. Five polymers achieved higher
      uptake and transfection efficacy with less toxicity than branched-PEI control.
      Surprisingly, acrylate-terminated base polymers were dramatically less
      efficacious than their end-capped versions, in terms of both uptake (1-3% for
      acrylate, 75-94% for end-capped) and transfection efficacy (0-1% vs 20-89%), even
      though there are minimal differences between acrylate and end-capped polymers in
      terms of DNA retardation in gel electrophoresis, particle size, zeta potential,
      and cytotoxicity. These studies further elucidate the role of polymer structure
      for gene delivery and highlight that small molecule end-group modification of a
      linear polymer can be critical for cellular uptake in a manner that is largely
      independent of polymer/DNA binding, particle size, and particle surface charge.

PMID- 22970910
TI  - Rare presentation of shock and acute mesenteric ischaemia secondary to acute
      adrenal insufficiency in an 11-year-old male.
AB  - An 11-year-old Caucasian male with history of abdominal pain, diarrhoea, fatigue,
      emesis and fever on the previous days presented with dehydratation, shock and
      acute mesenteric ischaemia. Final diagnosis of Addison's disease was made.

PMID- 22970909
TI  - Rapid transition from inhaled iloprost to inhaled treprostinil in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Inhaled treprostinil is a prostacyclin analog approved for the
      treatment of pulmonary arterial hypertension (PAH) that may provide a more
      convenient treatment option for patients receiving inhaled iloprost while
      maintaining the clinical benefit of inhaled prostacyclin therapy. AIMS: In this
      open-label safety study, 73 PAH patients were enrolled with primarily World
      Health Organization Class II (56%) or III (42%) symptoms. At baseline, most
      patients (93%) were receiving 5 MUg of iloprost per dose but 38% of patients
      reported a dosing frequency below the labeled rate of 6-9 times daily. Patients
      initiated inhaled treprostinil at 3 breaths four times daily (qid) at the
      immediate next scheduled iloprost dose. The primary objective was to assess the
      safety of rapid transition from iloprost to inhaled treprostinil; clinical status
      and quality of life were also assessed. RESULTS: Most patients (84%) achieved the
      target treprostinil dose of 9 breaths qid and remained on study until transition
      to commercial therapy (89%). The most frequent adverse events (AEs) were cough
      (74%), headache (44%), and nausea (30%), and five patients prematurely
      discontinued study drug due to AE (n = 3), disease progression (n = 1), or death
      (n = 1). At week 12, the time spent on daily treatment activities was reduced
      compared to baseline, with a mean total savings of 1.4 h per day. Improvements
      were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N
      terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge
      Pulmonary Hypertension Outcome Review (all domains P < 0.001). CONCLUSIONS:
      Pulmonary arterial hypertension patients can be safely transitioned from inhaled
      iloprost to inhaled treprostinil while maintaining clinical status.

PMID- 22970911
TI  - Childhood cruelty to animals in China: the relationship with psychological
      adjustment and family functioning.
AB  - BACKGROUND: The current study broadened the general scope of research conducted
      on childhood cruelty to animals by examining the association between
      psychological adjustment, family functioning and animal cruelty in an Eastern
      context, China. METHOD: The mothers and fathers of 729 children attending primary
      school in Chengdu, China participated in this study. Each parent completed the
      Strengths and Difficulties Questionnaire, the Chinese Family Assessment
      Instrument, and the Children's Attitudes and Behaviours towards Animals
      questionnaire. RESULTS: Findings from an actor partner interdependence model
      demonstrated that parents' ratings of family functioning and of their child's
      externalizing coping style predicted only modest amounts of variance in animal
      cruelty. In particular, parents' ratings of their child's externalizing coping
      style most consistently predicted animal cruelty. Family functioning, fathers'
      ratings in particular, played a minor role, more so for boys compared with girls.
      CONCLUSION: This study provided the first insight into childhood animal cruelty
      in China, and suggests that further research may enhance our understanding of
      these phenomena.

PMID- 22970912
TI  - gamma-Amino alcohols via organocascade reactions involving dienamine catalysis.
AB  - Whereas cascade reactions catalyzed by secondary amines combine iminium- and/or
      enamine-catalyzed reactions, we introduce the feasibility of combining these
      modes of catalysis with dienamine-catalysis as a new general mechanism for
      cascade reactions. Enantioenriched beta-functionalized-gamma-amino alcohols were
      produced from simple achiral enals in one flask by combining dienamine- and
      iminium-catalyzed intermolecular reactions. Reaction products are precursors of
      gamma-amino acids, gamma-lactams, and pyrrolidines; one was employed in a
      synthesis of gamma-amino acid (S)-vigabatrin, the bioactive enantiomer of Sabril.

PMID- 22970913
TI  - Thermography, therapeutic exercise, and individuals with diabetes.

PMID- 22970914
TI  - Impact of basic fibroblast growth factor on healing of tympanic membrane
      perforations due to direct penetrating trauma: a prospective non
      blinded/controlled study.
AB  - OBJECTIVE: To investigate the effect of direct application of basic fibroblast
      growth factor (bFGF) on healing of tympanic membrane perforations due to direct
      traumatic penetration through the external auditory canal. DESIGN: A prospective
      non-blinded controlled study. SETTING: University-affiliated teaching hospital.
      PARTICIPANTS: In total, 104 patients with small [<25%] penetrating perforations
      were recruited. They were alternatively allocated to two groups: Control
      (spontaneous healing, n = 51) and FGF treatment (direct application of bFGF drops
      in the clinic and repeated daily by the patient, n = 53). OUTCOMES: Perforation
      closure rate and time and hearing gain were recorded and compared between the two
      groups. Information on earache, dizziness and facial paralysis was also
      collected. RESULTS: In total, 93 (89%) patients were finally analysed. The
      closure rate at 3 m of the perforations in the control spontaneous healing and
      bFGF treatment groups were 77% and 100%, respectively; the difference was
      statistically significant (P = 0.01). The average closure time was 43.1 +/- 2.5
      days (range, 17-57 days) for control patients, which was significantly longer (P
      < 0.01) than that for the bFGF-treated patients (12.6 +/- 1.2 days; range, 3-21
      days). The mean hearing improvement at 3 m was not significantly different
      between the FGF treatment and control groups (1.7 +/- 2.4 dB vs 11.5 +/- 1.9 dB,
      P > 0.05). No significant difference was observed in earache, dizziness and
      facial paralysis between two groups. CONCLUSIONS: Direct application of bFGF may
      offer an effective topical management of penetrating traumatic tympanic membrane
      perforations, particularly for small-sized perforations.

PMID- 22970915
TI  - Long-chain 3,4-ethylenedioxythiophene/thiophene oligomers and semiconducting thin
      films prepared by their electropolymerization.
AB  - A series of soluble H-terminated conjugated oligomers incorporating 3,4
      ethylenedioxythiophene (EDOT) combined with a small number of thiophene units and
      ranging in length from four to eight EDOT/thiophene groups was prepared with the
      ultimate goal to investigate if facile formation of a reactive trication radical
      species would enable electrochemical polymerization of such long-chain oligomers.
      Spectroscopic and electrochemical studies of the oligomers revealed some general
      dependencies of their electronic properties on the total number and position of
      EDOT groups. It was the number of consecutive EDOT units rather than total number
      of these units which was found to have the most profound effect on electronic
      energy gap and conjugation length. This influence originates from the especially
      strong planarization induced in the conjugated backbone by the incorporation of
      EDOT units. In contrast, incorporation of thiophene units was found to result in
      loss of the conformational stabilization. This phenomenon was analyzed using the
      natural bond orbital computational approach, which revealed the predominantly
      hyperconjugative nature of the EDOT-induced conformational stabilization. Whereas
      shorter oligomers, in agreement with the general consensus, were found to be
      inert toward electrochemical polymerization due to low reactivity of
      electrochemically generated cation radical and dication species, the longest
      oligomer showed an unprecedentedly efficient electropolymerization to yield a
      stable thin film of an electroactive polymer. The efficient electropolymerization
      of the long-chain oligomer was found to be in agreement with the formation of a
      reactive trication radical species. The electronic and spectral properties of the
      resulting semiconducting polymer film were studied by various electrochemical and
      spectroelectrochemical methods, as well as conductive probe AFM technique, and
      revealed a number of unusual features (such as electrical rectifying switching
      behavior) consistent with the possibility of increased molecular order in this
      material.

PMID- 22970916
TI  - Double smectic self-assembly in block copolypeptide complexes.
AB  - We show double smectic-like self-assemblies in the solid state involving
      alternating layers of different polypeptide alpha-helices. We employed rod-coil
      poly(gamma-benzyl l-glutamate)-block-poly(l-lysine) (PBLG-b-PLL) as the polymeric
      scaffold, where the PLL amino residues were ionically complexed to di-n-butyl
      phosphate (diC4P), di(2-ethylhexyl) phosphate (diC2/6P), di(2-octyldodecyl)
      phosphate (diC8/12P), or di-n-dodecyl phosphate (diC12P), forming PBLG-b
      PLL(diC4P), PBLG-b-PLL(diC2/6P), PBLG-b-PLL(diC8/12P), and PBLG-b-PLL(diC12P)
      complexes, respectively. The complexes contain PBLG alpha-helices of fixed
      diameter and PLL-surfactant complexes adopting either alpha-helices of tunable
      diameters or beta-sheets. For PBLG-b-PLL(diC4P), that is, using a surfactant with
      short n-butyl tails, both blocks were alpha-helical, of roughly equal diameter
      and thus with minor packing frustrations, leading to alternating PBLG and
      PLL(diC4P) smectic layers of approximately perpendicular alignment of both types
      of alpha-helices. Surfactants with longer and branched alkyl tails lead to an
      increased diameter of the PLL-surfactant alpha-helices. Smectic alternating PBLG
      and PLL(diC2/6P) layers involve larger packing frustration, which leads to poor
      overall order and suggests an arrangement of tilted PBLG alpha-helices. In PBLG-b
      PLL(diC8/12P), the PLL(diC8/12P) alpha-helices are even larger and the overall
      structure is poor. Using a surfactant with two linear n-dodecyl tails leads to
      well-ordered beta-sheet domains of PLL(diC12P), consisting of alternating PLL and
      alkyl chain layers. This dominates the whole assembly, and at the block
      copolypeptide length scale, the PBLG alpha-helices do not show internal order and
      have poor organization. Packing frustration becomes an important aspect to design
      block copolypeptide assemblies, even if frustration could be relieved by
      conformational imperfections. The results suggest pathways to control
      hierarchical liquid-crystalline assemblies by competing interactions and by
      controlling molecular packing frustrations.

PMID- 22970917
TI  - Isotopic fingerprints of anthropogenic molybdenum in lake sediments.
AB  - We measured the molybdenum isotope compositions (delta(98)Mo) of well-dated
      sediment cores from two lakes in eastern Canada in an effort to distinguish
      between natural and anthropogenic contributions to these freshwater aquatic
      systems. Previously, Chappaz et al. (1) ascribed pronounced 20th-century Mo
      concentration enrichments in these lakes to anthropogenic inputs. delta(98)Mo
      values in the deeper sediments (reflecting predominantly natural Mo sources)
      differ dramatically between the two lakes: -0.32 +/- 0.170/00 for oxic Lake
      Tantare and +0.64 +/- 0.090/00 for anoxic Lake Vose. Sediment layers previously
      identified as enriched in anthropogenic Mo, however, reveal significant
      delta(98)Mo shifts of +/- 0.30/00, resulting in isotopically heavier values of
      +0.05 +/- 0.180/00 in Lake Tantare and lighter values of +0.31 +/- 0.030/00 in
      Lake Vose. We argue that anthropogenic Mo modifies the isotopic composition of
      the recent sediments, and we determine delta(98)Mo(anthropogenic) values of 0.1
      +/- 0.10/00 (Lake Vose) and 0.2 +/- 0.20/00 (Lake Tantare). These calculated
      inputs are consistent with the delta(98)Mo of molybdenite (MoS(2)) likely
      delivered to the lakes via smelting of porphyry copper deposits (Lake Vose) or
      through combustion of coal and oil also containing Mo (Lake Tantare). Our results
      confirm the utility of Mo isotopes as a promising fingerprint of human impacts
      and perhaps the specific sources of contamination. Importantly, the magnitudes of
      the anthropogenic inputs are large enough, relative to the natural Mo cycles in
      each lake, to have an impact on the microbiological communities.

PMID- 22970918
TI  - The variability of genetic disease.

PMID- 22970920
TI  - Punishing health care fraud--is the GSK settlement sufficient?

PMID- 22970921
TI  - Abstracts of the European Congress of Immunology. September 5-8, 2012. Glasgow,
      Scotland, United Kingdom.

PMID- 22970919
TI  - Phenotypic heterogeneity of genomic disorders and rare copy-number variants.
AB  - BACKGROUND: Some copy-number variants are associated with genomic disorders with
      extreme phenotypic heterogeneity. The cause of this variation is unknown, which
      presents challenges in genetic diagnosis, counseling, and management. METHODS: We
      analyzed the genomes of 2312 children known to carry a copy-number variant
      associated with intellectual disability and congenital abnormalities, using array
      comparative genomic hybridization. RESULTS: Among the affected children, 10.1%
      carried a second large copy-number variant in addition to the primary genetic
      lesion. We identified seven genomic disorders, each defined by a specific copy
      number variant, in which the affected children were more likely to carry multiple
      copy-number variants than were controls. We found that syndromic disorders could
      be distinguished from those with extreme phenotypic heterogeneity on the basis of
      the total number of copy-number variants and whether the variants are inherited
      or de novo. Children who carried two large copy-number variants of unknown
      clinical significance were eight times as likely to have developmental delay as
      were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07;
      P=2.11*10(-38)). Among affected children, inherited copy-number variants tended
      to co-occur with a second-site large copy-number variant (Spearman correlation
      coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders
      of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers
      to transmit second-site copy-number variants to their offspring (P=0.02).
      CONCLUSIONS: Multiple, large copy-number variants, including those of unknown
      pathogenic significance, compound to result in a severe clinical presentation,
      and secondary copy-number variants are preferentially transmitted from maternal
      carriers. (Funded by the Simons Foundation Autism Research Initiative and the
      National Institutes of Health.).

PMID- 22970922
TI  - The heart in Duchenne muscular dystrophy: early detection of contractile
      performance alteration.
AB  - Progressive cardiomyopathy is a major cause of death in Duchenne muscular
      dystrophy (DMD) patients. Coupling between Ca(2+) handling and contractile
      properties in dystrophic hearts is poorly understood. It is also not clear
      whether developing cardiac failure is dominated by alterations in Ca(2+) pathways
      or more related to the contractile apparatus. We simultaneously recorded force
      and Ca(2+) transients in field-stimulated papillary muscles from young (10-14
      weeks) wild-type (wt) and dystrophic mdx mice. Force amplitudes were fivefold
      reduced in mdx muscles despite only 30% reduction in fura-2 ratio amplitudes.
      This indicated mechanisms other than systolic Ca(2+) to additionally account for
      force decrements in mdx muscles. pCa-force relations revealed decreased mdx
      myofibrillar Ca(2+) sensitivity. 'In vitro' motility assays, studied in mdx
      hearts here for the first time, showed significantly slower sliding velocities.
      mdx MLC/MHC isoforms were not grossly altered. Dystrophic hearts showed
      echocardiography signs of early ventricular wall hypertrophy with a significantly
      enlarged end-diastolic diameter 'in vivo'. However, fractional shortening was
      still comparable to wt mice. Changes in the contractile apparatus satisfactorily
      explained force drop in mdx hearts. We give first evidence of early hypertrophy
      in mdx mice and possible mechanisms for already functional impairment of cardiac
      muscle in DMD.

PMID- 22970923
TI  - Urodynamic findings in women with insensible incontinence.
AB  - OBJECTIVES: To define the urodynamic study findings among women with insensible
      urinary incontinence. METHODS: Women complaining of insensible incontinence who
      underwent urodynamics at our center were identified. Coexisting symptoms of
      stress incontinence, urgency incontinence and/or mixed incontinence were
      recorded. The primary outcome was the urodynamic study finding. Urodynamic stress
      incontinence, detrusor overactivity incontinence, combination of both or neither
      (no incontinence) were the possible diagnoses. RESULTS: A total of 58% of
      patients had insensible incontinence alone and 42% had insensible incontinence
      combined with other urinary incontinence symptoms. Of the patients with
      insensible incontinence alone, 37% had no incontinence on urodynamics, whereas
      urodynamic stress incontinence was diagnosed in 52%. Isolated urodynamic stress
      incontinence was found in 73% of patients with insensible and stress incontinence
      symptoms. In patients with insensible plus urgency incontinence, isolated
      detrusor overactivity incontinence and detrusor overactivity incontinence with
      urodynamic stress incontinence were found in the same percentage of women (40%
      each). In patients with symptoms including stress urinary incontinence, stress
      incontinence was the predominant urodynamic finding. CONCLUSIONS: In patients who
      have incontinence symptoms in addition to insensible incontinence, these symptoms
      are highly predictive of urodynamic findings. In particular, women with
      insensible incontinence, concomitant stress incontinence symptoms are most
      predictive of urodynamic findings (i.e. urodynamic stress urinary incontinence).
      In contrast, where insensible incontinence represents the only symptom,
      urodynamic findings vary widely, with a significant proportion having non
      diagnostic studies.

PMID- 22970925
TI  - Dental fear and satisfaction with dental services in Switzerland.
AB  - OBJECTIVES: Dental satisfaction is associated with continuity of dental care,
      compliance with dentist advice, and positive health outcomes. It is expected that
      people with higher dental fear might have less dental satisfaction because of
      more negative dental experiences. The objective of this study was to examine
      satisfaction and reasons for satisfaction with dental practitioners in
      Switzerland and variations by dental fear. METHODS: A national sample of 1,129
      Swiss residents aged 15-74 (mean = 43.2 years) completed a personal interview at
      their home with questions assessing dental fear, dental service use, general
      satisfaction with their dentist, and reasons for satisfaction or dissatisfaction.
      RESULTS: Overall, 47.9 percent of participants responded that they were satisfied
      with their dentist and 47.6 percent that they were very satisfied. Satisfaction
      differed significantly by gender, language spoken, region of residence, and
      educational attainment. Greater dental fear was significantly associated with
      greater dissatisfaction with the dentist. The percentage of people who were very
      satisfied with the dentist ranged from 56.0 percent among people with no fear to
      30.5 percent for participants with "quite a lot" of fear but was higher (44.4
      percent) for people who stated that they were "very much" afraid of the dentist.
      The most common reasons attributed for satisfaction with dentists were
      interpersonal characteristics of the dentist and staff. People with "quite a lot"
      of fear were found to endorse these sentiments least. CONCLUSIONS: Although
      higher dental fear was associated with more dissatisfaction with the dentist, the
      level of satisfaction among fearful individuals in Switzerland is still high.

PMID- 22970924
TI  - Time course of cocaine-induced behavioral and neurochemical plasticity.
AB  - Factors that result in augmented reinstatement, including increased withdrawal
      period duration and high levels of cocaine consumption, may provide insight into
      relapse vulnerability. The neural basis of augmented reinstatement may arise from
      more pronounced changes in plasticity required for reinstatement and/or the
      emergence of plasticity expressed only during a specific withdrawal period or
      under specific intake conditions. In this study, we examined the impact of
      withdrawal period duration and cocaine intake on the magnitude of cocaine-primed
      reinstatement and extracellular glutamate in the nucleus accumbens, which has
      been shown to be required for cocaine-primed reinstatement. Rats were assigned to
      self-administer under conditions resulting in low (2 hours/day; 0.5
      mg/kg/infusion, IV) or high (6 hours/day; 1.0 mg/kg/infusion, IV) levels of
      cocaine intake. After 1, 21 or 60 days of withdrawal, drug seeking and
      extracellular glutamate levels in the nucleus accumbens were measured before and
      after a cocaine injection. Cocaine-reinstated lever pressing and elevated
      extracellular glutamate at every withdrawal time point tested, which is
      consistent with the conclusion that increased glutamatergic signaling in the
      nucleus accumbens, is required for cocaine-induced reinstatement. Interestingly,
      high-intake rats exhibited augmented reinstatement at every time point tested,
      yet failed to exhibit higher levels of cocaine-induced increases in extracellular
      glutamate relative to low-intake rats. Our current data indicate that augmented
      reinstatement in high-intake rats is not due to relative differences in
      extracellular levels of glutamate in the nucleus accumbens, but rather may stem
      from intake-dependent plasticity. 

PMID- 22970926
TI  - Adherence and persistence with non-nucleoside reverse transcriptase inhibitor
      based antiretroviral regimens.
AB  - OBJECTIVE: The objective of this study was to examine adherence and persistency
      in HIV patients initiating first-line combination antiretroviral therapy (cART)
      with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen.
      METHODS: Using US health insurance records, the authors identified all persons
      aged >= 18 years with HIV, who began NNRTI-based cART between 1 January 2003 and
      30 September 2009. They examined adherence using proportion of days covered
      (PDC), and non-persistency based on evidence of discontinuation, switching or
      augmentation. Differences in non-adherence (1 - PC) and non-persistency were
      compared over 12 months, between three treatment groups: i) efavirenz,
      emtricitabine and tenofovir as a fixed-dose combination ('EFV/FTC/TDF'); ii) EFV
      based regimens other than EFV/TDF/FTC, with >= 2 NRTIs ('EFV + >= 2 NRTIs'); and
      iii) nevirapine-based regimens with >= 2 NRTIs (NVP + >= 2 NRTIs). RESULTS: There
      were 1874 patients receiving EFV/FTC/TDF, 893 receiving EFV + >= 2 NRTIs and 207
      receiving NVP + >= 2 NRTIs. Adherence was lower for both EFV + >= 2 NRTIs and NVP
      + >= 2 NRTIs than for EFV/FTC/TDF (rate ratio (RR) = 1.57 and 2.01, respectively;
      both p < 0.01), while non-persistency was higher (hazard ratio (HR) = 1.56, p <
      0.01 and 1.70, p < 0.01, respectively). CONCLUSION: Adherence and persistency may
      differ between NNRTI-based regimens; additional analyses are needed to understand
      the reasons for these differences.

PMID- 22970927
TI  - Tyrosine deprotonation yields abundant and selective backbone cleavage in peptide
      anions upon negative electron transfer dissociation and ultraviolet
      photodissociation.
AB  - Tyrosine deprotonation in peptides yields preferential electron detachment upon
      NETD or UVPD, resulting in prominent N-Calpha bond cleavage N-terminal to the
      tyrosine residue. UVPD of iodo-tyrosine-modified peptides was used to generate
      localized radicals on neutral tyrosine side chains by homolytic cleavage of the C
      I bond. Subsequent collisional activation of the radical species yielded the same
      preferential cleavage of the adjacent N-terminal N-Calpha bond. LC-MS/MS analysis
      of a tryptic digest of BSA demonstrated that these cleavages are regularly
      observed for peptides when using high-pH mobile phases.

PMID- 22970928
TI  - Polygalins D-G, four new flavonol glycosides from the aerial parts of Polygala
      sibirica L. (Polygalaceae).
AB  - Four new flavonol glycosides (1-4), polygalins D-G, together with 12 known
      flavonoids (5-16) were isolated from the aerial parts of Polygala sibirica L. The
      chemical structures of these compounds were characterised by NMR and ESI-MS
      spectroscopic data and acid hydrolysis results. This report is a continuous
      research work on the systematic chemical investigations of plants of the genus
      Polygala in our laboratory.

PMID- 22970929
TI  - Association of markers of chronic viral hepatitis and blood mercury levels in US
      reproductive-age women from NHANES 2001-2008: a cross-sectional study.
AB  - BACKGROUND: Methylmercury (MeHg) is a neurotoxin primarily found in seafood;
      exposures in reproductive-age women are of concern due to vulnerability of the
      developing fetus. MeHg is mainly eliminated via an enterohepatic cycle involving
      the liver and gallbladder. Dysfunction in these organs has been associated with
      slower MeHg elimination in laboratory animals. We hypothesized that women testing
      positive for chronic hepatitis B (HBV) or C (HCV), both associated with risk of
      longer-term liver and gallbladder impairment, would have higher total blood
      mercury (TBHg) concentrations than those negative for the viruses, reflecting
      slower MeHg elimination. METHODS: Geometric mean (GM) TBHg levels from a
      representative sample of over 5,000 seafood-consuming, reproductive-age women
      from eight years (2001-2008) of the US NHANES survey were compared by viral
      hepatitis status (as determined by serological assay) using multiple linear
      regression. Adjustment was made for estimated MeHg intake from seafood
      consumption, social and demographic variables and other predictors. RESULTS:
      Women with chronic HBV had 1.52 (95% CI 1.13, 2.05, p < 0.01) times the GM TBHg
      of women who had not come into contact with the virus. The positive association
      was strongest in those with most severe disease. A modest negative association
      was found with HCV markers. CONCLUSIONS: While study design prevents inferences
      on causality, the finding that MeHg biomarkers differ by hepatitis status in this
      population suggests viral hepatitis may alter the pace of MeHg elimination.
      Offspring of HBV-infected seafood-consuming women may be at higher risk of MeHg
      induced developmental delays than offspring of those uninfected. Possible reasons
      for the unanticipated negative association with HCV are explored.

PMID- 22970931
TI  - Study of fluorescence resonance energy transfer in zwitterionic micelle: ionic
      liquid-induced changes in FRET parameters.
AB  - The fluorescence resonance energy transfer (FRET) using Coumarin-153 (C-153) as
      the donor and Rhodamine 6G (R6G) as the acceptor is studied in an aqueous
      solution of N-hexadecyl-N,N-dimethylammonio-1-propanesulfonate (SB-16) micelles
      by steady-state and picosecond time-resolved fluorescence spectroscopy. We have
      determined the rate of FRET (k(FRET)) from the rise of the acceptor (R6G)
      emission. In the absence of donor (C-153), the acceptor (R6G) displays a single
      exponential decay with average lifetime of 4.77 ns, whereas in presence of donor
      (C-153), the acceptor (R6G) exhibits a biexponential fluorescence transient
      having a distinct rise component of 0.94 ns and decay component of 5.16 ns. We
      have carried out a comparative study of changes in FRET parameters upon addition
      of three different ionic liquids (ILs), 1-ethyl-3-methylimidazolium ethylsulfate
      [C(2)mim][C(2)SO(4)], 1-ethyl-3-methylimidazolium n-butylsulfate
      [C(2)mim][C(4)SO(4)], and 1-ethyl-3-methylimidazolium n-hexylsulfate
      [C(2)mim][C(6)SO(4)], where each ionic liquid bears the same cationic part and
      the anionic parts differ in the alkyl chain length only. It has been observed
      that with gradual addition of the ILs [C(2)mim][C(2)SO(4)], [C(2)mim][C(4)SO(4)],
      and [C(2)mim][C(6)SO(4)], the rise component gradually decreases and the rate of
      FRET (k(FRET)) gradually increases. The k(FRET) was found to be 1.06 * 10(9) s(
      1) in 28 mM aqueous SB-16 micelles. With the addition of 100 mM
      [C(2)mim][C(2)SO(4)], the k(FRET) increases by a factor of 1.33 (1.41 * 10(9) s(
      1)), whereas with the addition of 100 mM [C(2)mim][C(6)SO(4)] it increases by a
      factor of 3.25 (3.45 * 10(9) s(-1)). This rapid increase in k(FRET) in the case
      of [C(2)mim][C(6)SO(4)] can be explained by our earlier observation ( Rao, V. G.;
      Ghatak, C.; Ghosh, S.; Mandal, S.; Sarkar, N. J. Phys. Chem. B2012, 116, 3690
      3698 ), where we have shown that with the addition of [C(2)mim][C(6)SO(4)], C-153
      moves toward the outer surface of the micelle. This movement of C-153 causes
      reduction in donor-acceptor distance and enhancement in FRET rate (k(FRET)). This
      is well-supported by the reduced donor-acceptor distance (R(DA)) observed with
      the addition of [C(2)mim][C(6)SO(4)]. The R(DA) was found to be 29.1 A in 28 mM
      aqueous SB-16 micelles. With the addition of 100 mM [C(2)mim][C(6)SO(4)], the
      R(DA) decreases to 24.8 A. With further increase in the concentration of
      [C(2)mim][C(6)SO(4)], the R(DA) decreases, but the time constant for the rise of
      acceptor emission decreases to such an extent that we are unable to observe it by
      our instrumental setup.

PMID- 22970930
TI  - Docking and molecular dynamics studies of peptide inhibitors of ornithine
      decarboxylase: a rate-limiting enzyme for the metabolism of Fusarium solani.
AB  - Fusarium solani causes a wide variety of diseases in plants. Polyamine
      biosynthesis is responsible for the growth and pathogenicity of the fungus. The
      initial step of this pathway involves the decarboxylation of ornithine to
      putrescine, and is catalyzed by the enzyme ornithine decarboxylase (ODC).
      Inhibiting this process may be a promising approach for the management of fungal
      disease in various crops. Therefore, there is a need to develop inhibitors of ODC
      that have higher binding capacity than ornithine. Fifteen peptides were designed
      and modeled based on physicochemical properties of residues in the active site of
      ODC. The peptide GLIWGNGPF showed the highest dock score. It is assumed that the
      de novo design of peptides could be a potential approach to inhibit polyamine
      biosynthesis. Molecular dynamics studies make an important contribution to
      understanding the effect of the binding of peptides and the stability of an ODC
      peptide complex system. An animated Interactive 3D Complement (I3DC) is available
      in Proteopedia at http://proteopedia.org/w/Journal:JBSD:8 . 

PMID- 22970932
TI  - Simulations of smog-chamber experiments using the two-dimensional volatility
      basis set: linear oxygenated precursors.
AB  - We use a two-dimensional volatility basis set (2D-VBS) box model to simulate
      secondary organic aerosol (SOA) mass yields of linear oxygenated molecules: n
      tridecanal, 2- and 7-tridecanone, 2- and 7-tridecanol, and n-pentadecane. A
      hybrid model with explicit, a priori treatment of the first-generation products
      for each precursor molecule, followed by a generic 2D-VBS mechanism for later
      generation chemistry, results in excellent model-measurement agreement. This
      strongly confirms that the 2D-VBS mechanism is a predictive tool for SOA modeling
      but also suggests that certain important first-generation products for major
      primary SOA precursors should be treated explicitly for optimal SOA predictions.

PMID- 22970933
TI  - Study protocol. IDUS - Instrumental delivery & ultrasound: a multi-centre
      randomised controlled trial of ultrasound assessment of the fetal head position
      versus standard care as an approach to prevent morbidity at instrumental
      delivery.
AB  - BACKGROUND: Instrumental deliveries are commonly performed in the United Kingdom
      and Ireland, with rates of 12 - 17% in most centres. Knowing the exact position
      of the fetal head is a pre-requisite for safe instrumental delivery.
      Traditionally, diagnosis of the fetal head position is made on transvaginal
      digital examination by delineating the suture lines of the fetal skull and the
      fontanelles. However, the accuracy of transvaginal digital examination can be
      unreliable and varies between 20% and 75%. Failure to identify the correct fetal
      head position increases the likelihood of failed instrumental delivery with the
      additional morbidity of sequential use of instruments or second stage caesarean
      section. The use of ultrasound in determining the position of the fetal head has
      been explored but is not part of routine clinical practice. METHODS/DESIGN: A
      multi-centre randomised controlled trial is proposed. The study will take place
      in two large maternity units in Ireland with a combined annual birth rate of
      13,500 deliveries. It will involve 450 nulliparous women undergoing instrumental
      delivery after 37 weeks gestation. The main outcome measure will be incorrect
      diagnosis of the fetal head position. A study involving 450 women will have 80%
      power to detect a 10% difference in the incidence of inaccurate diagnosis of the
      fetal head position with two-sided 5% alpha. DISCUSSION: It is both important and
      timely to evaluate the use of ultrasound to diagnose the fetal head position
      prior to instrumental delivery before routine use can be advocated. The overall
      aim is to reduce the incidence of incorrect diagnosis of the fetal head position
      prior to instrumental delivery and improve the safety of instrumental deliveries.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN72230496.

PMID- 22970934
TI  - Teaching an old dogma new tricks: twenty years of Shc adaptor signalling.
AB  - Shc (Src homology and collagen homology) proteins are considered prototypical
      signalling adaptors in mammalian cells. Consisting of four unique members, ShcA,
      B, C and D, and multiple splice isoforms, the family is represented in nearly
      every cell type in the body, where it engages in an array of fundamental
      processes to transduce environmental stimuli. Two decades of investigation have
      begun to illuminate the mechanisms of the flagship ShcA protein, whereas much
      remains to be learned about the newest discovery, ShcD. It is clear, however,
      that the distinctive modular architecture of Shc proteins, their promiscuous
      phosphotyrosine-based interactions with a multitude of membrane receptors,
      involvement in central cascades including MAPK (mitogen-activated protein kinase)
      and Akt, and unconventional contributions to oxidative stress and apoptosis all
      require intricate regulation, and underlie diverse physiological function. From
      early cardiovascular development and neuronal differentiation to lifespan
      determination and tumorigenesis, Shc adaptors have proven to be more ubiquitous,
      versatile and dynamic than their structures alone suggest.

PMID- 22970935
TI  - Mechanistic differences in permeation behavior of supersaturated and solubilized
      solutions of carbamazepine revealed by nuclear magnetic resonance measurements.
AB  - A solid dispersion (SPD) of carbamazepine (CBZ) with hydroxypropyl
      methylcellulose acetate succinate (HPMC-AS) was prepared by the spray drying
      method. The apparent solubility (37  degrees C, pH 7.4) of CBZ observed with the
      SPD was over 3 times higher than the solubility of unprocessed CBZ. The
      supersaturated solution was stable for 7 days. A higher concentration of CBZ in
      aqueous medium was also achieved by mixing with Poloxamer 407 (P407), a
      solubilizing agent. From permeation studies of CBZ using Caco-2 monolayers and
      dialysis membranes, we observed improved CBZ permeation across the membrane in
      the supersaturated solution of CBZ/HPMC-AS SPD. On the contrary, the CBZ
      solubilized P407 solution exhibited poor permeation by CBZ. The chemical shifts
      of CBZ on the (1)H NMR spectrum from CBZ/HPMC-AS SPD solution were not altered
      significantly by coexistence with HPMC-AS. In contrast, an upfield shift of CBZ
      was observed in the CBZ/P407 solution. The spin-lattice relaxation time (T(1))
      over spin-spin relaxation time (T(2)) indicated that the mobility of CBZ in the
      HPMC-AS solution was much lower than that in water. Meanwhile, the mobility of
      CBZ in P407 solution was significantly higher than that in water. NMR data
      indicate that CBZ does not strongly interact with HPMC-AS. CBZ mobility was
      suppressed due to self-association and microviscosity around CBZ, which do not
      affect permeation behavior. Most of the CBZ molecules in the CBZ/P407 solution
      were solubilized in the hydrophobic core of P407, and a few were free to permeate
      the membrane. The molecular state of CBZ, as evaluated by NMR measurements,
      directly correlated with permeation behavior.

PMID- 22970936
TI  - Neuroprotective effects of flax lignan against NMDA-induced neurotoxicity in
      vitro.
AB  - AIMS: Flax Lignan (FLL), a chemical widespread within the plant and animal
      kingdoms, has antioxidant, antiinfectious, and antitumor activities. However,
      little is known about the effects of FLL on the central nervous system (CNS).
      METHODS: The neuroprotective actions of FLL against N-methyl-d-aspartate (NMDA)
      are investigated in primary cultured cortical neurons by MTT assay. The
      expression levels of proteins related to apoptosis and GluN2-containing receptor
      were detected by Western blot analysis. Intracellular Ca(2+)  was measured under
      a confocal laser scanning microscope. RESULTS: After challenged with 100 MUM NMDA
      for 30 min, loss of cell viability and excessive apoptotic cell death were
      observed in cultured cortical neurons. FLL protected the neurons against the NMDA
      induced cell loss in a concentration-dependent manner. FLL also significantly
      inhibited the neuronal apoptosis induced by NMDA exposure through reversing
      intracellular concentration of Ca(2+)  overload and balancing of Bcl-2 and Bax
      expression. Furthermore, FLL significantly reversed the upregulation of GluN2B
      containing NMDA receptors by exposure to NMDA, but did not affect the expression
      of GluN2A-containing NMDA receptor. CONCLUSIONS: These findings suggest that FLL
      protects cortical neurons by inhibiting the expression of GluN2B-containing NMDA
      receptor and regulating the Bcl-2 family.

PMID- 22970937
TI  - Salicylanilide inhibitors of Toxoplasma gondii.
AB  - Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye
      disease, brain disease, and death, especially in congenitally infected and immune
      compromised people. Novel medicines effective against both active and latent
      forms of the parasite are greatly needed. The current study focused on the
      discovery of such medicines by exploring a family of potential inhibitors whose
      antiapicomplexan activity has not been previously reported. Initial screening
      efforts revealed that niclosamide, a drug approved for anthelmintic use,
      possessed promising activity in vitro against T. gondii. This observation
      inspired the evaluation of the activity of a series of salicylanilides and
      derivatives. Several inhibitors with activities in the nanomolar range with no
      appreciable in vitro toxicity to human cells were identified. An initial
      structure-activity relationship was explored. Four compounds were selected for
      evaluation in an in vivo model of infection, and two derivatives with potentially
      enhanced pharmacological parameters demonstrated the best activity profiles.

PMID- 22970938
TI  - Verbal definitions of familiar objects in blind children reflect their peculiar
      perceptual experience.
AB  - BACKGROUND: The aim of the present study was to examine to what extent the verbal
      definitions of familiar objects produced by blind children reflect their peculiar
      perceptual experience and, in consequence, differ from those produced by sighted
      children. METHODS: Ninety-six visually impaired children, aged between 6 and 14
      years, and 32 age-matched sighted children had to define 10 words denoting
      concrete animate or inanimate familiar objects. RESULTS: The blind children
      evoked the tactile and auditory characteristics of objects and expressed personal
      perceptual experiences in their definitions. The sighted children relied on
      visual perception, and produced more visually oriented verbalism. In contrast, no
      differences were observed between children in their propensity to include
      functional attributes in their verbal definitions. CONCLUSIONS: The results are
      discussed in line with embodied views of cognition that postulate mandatory
      perceptuomotor processing of words during access to their meaning.

PMID- 22970939
TI  - Stage-specific impact of extended versus standard pelvic lymph node dissection in
      radical cystectomy.
AB  - OBJECTIVES: To evaluate the impact of an extended versus a standard pelvic lymph
      node dissection on disease-free survival and cancer-specific survival of patients
      with non-metastatic muscle-invasive urothelial carcinoma of the bladder treated
      with radical cystectomy. METHODS: We retrospectively analyzed data of 933
      patients collected in two prospectively-maintained institutional databases
      between 2002 and 2010. Patients who met inclusion criteria (high-grade urothelial
      carcinoma, have not undergone neoadjuvant treatments, have not undergone salvage
      cystectomy) were included for analysis. The upper boundary was the iliac
      bifurcation for standard lymph-node dissection and the aortic bifurcation for the
      extended lymph node dissection, respectively. Univariable and multivariable Cox
      regression analyses were carried out to identify independent predictors of
      disease-free survival and cancer-specific survival and, subsequently, the effect
      of extended lymph node dissection was determined with a multivariable Cox
      analysis after stratifying for significant covariates. RESULTS: At multivariable
      analysis, once adjusted for the effect of the other covariates, extended lymph
      node dissection was an independent predictor of disease-free survival (hazard
      ratio 1.95, P < 0.001) and cancer-specific survival (hazard ratio 1.80, P <
      0.001). The benefit of an extended pelvic lymph node dissection on disease-free
      survival and cancer-specific survival was significant across all pT stages (all P
      < 0.05) except for pT <2 and across all pN stages (pN = 0, P = 0.011 and P =
      0.034 for disease-free survival and cancer-specific survival, respectively; pN1
      and pN2, all P < 0.001). CONCLUSIONS: The staging accuracy and the survival
      benefit provided by extended pelvic lymph node dissection suggests the adoption
      of this template as the standard template for patients with muscle-invasive
      urothelial carcinoma of the bladder undergoing radical cystectomy.

PMID- 22970940
TI  - The skull base multidisciplinary team approach: our experience over the first
      year in three hundred and seventeen patients.

PMID- 22970941
TI  - Editorial perspective: Autism spectrum disorders in DSM-5--an historical
      perspective and the need for change.

PMID- 22970942
TI  - Recognizing conscience in abortion provision.

PMID- 22970943
TI  - There is more to life than death.

PMID- 22970944
TI  - PTEN mutations as a cause of constitutive insulin sensitivity and obesity.
AB  - BACKGROUND: Epidemiologic and genetic evidence links type 2 diabetes, obesity,
      and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has
      roles in both cellular growth and metabolic signaling. Germline PTEN mutations
      cause a cancer-predisposition syndrome, providing an opportunity to study the
      effect of PTEN haploinsufficiency in humans. METHODS: We measured insulin
      sensitivity and beta-cell function in 15 PTEN mutation carriers and 15 matched
      controls. Insulin signaling was measured in muscle and adipose-tissue biopsy
      specimens from 5 mutation carriers and 5 well-matched controls. We also assessed
      the effect of PTEN haploinsufficiency on obesity by comparing anthropometric
      indexes between the 15 patients and 2097 controls from a population-based study
      of healthy adults. Body composition was evaluated by means of dual-emission x-ray
      absorptiometry and skinfold thickness. RESULTS: Measures of insulin resistance
      were lower in the patients with a PTEN mutation than in controls (e.g., mean
      fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per
      liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of
      hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among
      carriers 2 times that among controls (P=0.009). The patients' insulin sensitivity
      could be explained by the presence of enhanced insulin signaling through the PI3K
      AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation
      carriers were obese as compared with population-based controls (mean body-mass
      index [the weight in kilograms divided by the square of the height in meters], 32
      [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in
      the patients was due to augmented adiposity without corresponding changes in fat
      distribution. CONCLUSIONS: PTEN haploinsufficiency is a monogenic cause of
      profound constitutive insulin sensitization that is apparently obesogenic. We
      demonstrate an apparently divergent effect of PTEN mutations: increased risks of
      obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced
      insulin sensitivity. (Funded by the Wellcome Trust and others.).

PMID- 22970946
TI  - Melioidosis.

PMID- 22970945
TI  - Waning protection after fifth dose of acellular pertussis vaccine in children.
AB  - BACKGROUND: In the United States, children receive five doses of diphtheria,
      tetanus, and acellular pertussis (DTaP) vaccine before 7 years of age. The
      duration of protection after five doses of DTaP is unknown. METHODS: We assessed
      the risk of pertussis in children in California relative to the time since the
      fifth dose of DTaP from 2006 to 2011. This period included a large outbreak in
      2010. We conducted a case-control study involving members of Kaiser Permanente
      Northern California who were vaccinated with DTaP at 47 to 84 months of age. We
      compared children with pertussis confirmed by a positive polymerase-chain
      reaction (PCR) assay with two sets of controls: those who were PCR-negative for
      pertussis and closely matched controls from the general population of health-plan
      members. We used logistic regression to examine the risk of pertussis in relation
      to the duration of time since the fifth DTaP dose. Children who received whole
      cell pertussis vaccine during infancy or who received any pertussis-containing
      vaccine after their fifth dose of DTaP were excluded. RESULTS: We compared 277
      children, 4 to 12 years of age, who were PCR-positive for pertussis with 3318 PCR
      negative controls and 6086 matched controls. PCR-positive children were more
      likely to have received the fifth DTaP dose earlier than PCR-negative controls
      (P<0.001) or matched controls (P=0.005). Comparison with PCR-negative controls
      yielded an odds ratio of 1.42 (95% confidence interval, 1.21 to 1.66), indicating
      that after the fifth dose of DTaP, the odds of acquiring pertussis increased by
      an average of 42% per year. CONCLUSIONS: Protection against pertussis waned
      during the 5 years after the fifth dose of DTaP. (Funded by Kaiser Permanente).

PMID- 22970947
TI  - Images in clinical medicine. Cerebral fat embolism.

PMID- 22970948
TI  - Case records of the Massachusetts General Hospital. Case 28-2012. A 30-year-old
      woman with shock and abdominal-wall necrosis after cesarean section.

PMID- 22970949
TI  - PTEN--linking metabolism, cell growth, and cancer.

PMID- 22970951
TI  - Screening flexible sigmoidoscopy for colon cancer.

PMID- 22970952
TI  - Screening flexible sigmoidoscopy for colon cancer.

PMID- 22970953
TI  - Screening flexible sigmoidoscopy for colon cancer.

PMID- 22970954
TI  - Screening flexible sigmoidoscopy for colon cancer.

PMID- 22970956
TI  - Glycemic control in youth with type 2 diabetes.

PMID- 22970958
TI  - Aspirin for prevention of thromboembolism recurrence.

PMID- 22970959
TI  - Aspirin for prevention of thromboembolism recurrence.

PMID- 22970960
TI  - Aspirin for prevention of thromboembolism recurrence.

PMID- 22970962
TI  - Prothrombin mutation conveying antithrombin resistance.

PMID- 22970963
TI  - Prothrombin mutation conveying antithrombin resistance.

PMID- 22970965
TI  - Human babesiosis.

PMID- 22970966
TI  - Human babesiosis.

PMID- 22970967
TI  - Three-dimensional virtual neck exploration before parathyroidectomy.

PMID- 22970971
TI  - Images in clinical medicine. Chvostek's and Trousseau's signs.

PMID- 22970972
TI  - Association of polymorphic markers of the catalase and superoxide dismutase genes
      with type 2 diabetes mellitus.
AB  - Our study aims at determining whether genetic polymorphisms of catalase (CAT
      1167C/T) and superoxide dismutase (SOD +35 A/C) could be associated with type 2
      diabetes mellitus (T2DM). The study was conducted on 105 Egyptian patients with
      T2DM and 115 control subjects. Genotypes were done by polymerase chain reaction
      restriction fragment length polymorphism methods. Homeostatic model assessment of
      insulin resistance (HOMA-IR), CAT and SOD activities, glycated hemoglobin, and
      insulin and lipid profiles were assessed. CAT and SOD activities were
      significantly decreased in T2DM compared with the control subjects. T allele of
      CAT and C allele of SOD1 were significant risk factors for T2DM. No effects of
      CAT or SOD1 gene polymorphisms on glycated haemoglobin or on HOMA-IR were found.
      With regard to the enzymes activities, only +35 A/C of SOD1 was related to SOD
      activity. Genetic variants C1167T of CAT gene and +35 A/C of SOD1 gene has no
      role in insulin resistance in T2DM.

PMID- 22970973
TI  - Construction of hollow and mesoporous ZnO microsphere: a facile synthesis and
      sensing property.
AB  - Mesoporous and hollow structure have been attracting increasing attention for
      their special properties and potential applications. Here we show a facile
      fabrication of hollow and mesoporous ZnO microsphere via a one-step wet chemical
      process using polyethylene glycol (PEG, MW 200) as the solvent and soft template.
      The morphology and structure of the products were characterized by using scanning
      electron microscopy and X-ray powder diffraction techniques. Thermal analysis and
      Fourier transform infrared spectroscopy techniques were also performed to show
      the properties of the precursor and annealed product. A possible growth mechanism
      of hollow and mesoporous ZnO microsphere was also proposed. The Brunauer-Emmett
      Teller surface area of ZnO microsphere is 28.5 m(2)g(-1) and the size of
      mesopores is about 10 nm. The Photoluminescence spectra of the as-synthesized ZnO
      hollow microspheres were also presented. The mesoporous and hollow structure
      enhance the gas sensitivity of ZnO microsphere, and the obtained ZnO microspheres
      based sensor has an excellent performance for precision detection of ethanol and
      acetone with low concentration.

PMID- 22970974
TI  - Loss of floral polymorphism in heterostylous Luculia pinceana (Rubiaceae): a
      molecular phylogeographic perspective.
AB  - Both deterministic and stochastic forces determine the representation and
      frequency of floral morphs in heterostylous plant populations. Phylogeographic
      analysis of molecular variation can provide information on the role of historical
      factors, including founder events, in affecting population morph structure. Here,
      we investigate geographical patterns of floral morph variation in a distylous
      shrub Luculia pinceana (Rubiaceae) by examining the relations between floral
      polymorphism and molecular (cpDNA and microsatellite) variation in 25 populations
      sampled throughout the distribution of the species in southwest China and
      adjacent countries. In 19 of the 25 populations, the frequency of floral morphs
      was not significantly different from the expected 1:1 ratio. The remaining
      populations were either L-morph biased (2) or monomorphic (4) for this form and
      were morphologically differentiated from the remaining populations in several
      floral traits, that is, corolla tube length, sex organ position and stigma-anther
      separation. Phylogeographic analysis supports the hypothesis that L. pinceana was
      initially split into west-central and eastern lineages in the Early Pleistocene
      (~1.982 Mya). A centrally located lineage composed of morph-biased and
      monomorphic populations appears to have been subsequently derived from the west
      central lineage, perhaps by a founder event after the last glacial maximum.
      Hypotheses to explain why these populations have not returned to equilibrium
      morph frequencies are considered.

PMID- 22970975
TI  - Helping clinicians deliver consistent HIV prevention counseling to their HIV
      infected patients.
AB  - The delivery of HIV risk assessment and behavioral counseling by clinicians in
      HIV clinical settings is one component in a comprehensive "positive prevention"
      strategy to help patients reduce their transmission risk behavior. Clinicians
      engage in behavioral prevention inconsistently, however, depending on whether
      patients are new to a practice or are established in regular care and on their
      attitudes and characteristics of their practices. We analyzed clinician reports
      of behavioral prevention delivered before and after participation in a large
      federal demonstration project of positive prevention interventions. The
      interventions that were part of this project were successful in increasing
      behavioral prevention among both new and returning patients. Prior to study
      interventions, clinicians reported counseling 69% of new patients and 52% of
      returning patients. In follow-up interviews 12 months after receiving training,
      clinicians reported delivering prevention messages to 5% more new patients and 9%
      of returning patients (both p<0.01). After 12 months, clinicians were more likely
      to engage in behavioral prevention if other providers in their sites were also
      involved. Clinicians agreeing that behavioral prevention was part of the clinic's
      mission were more likely to conduct it. The interventions were successful in
      mitigating the influence of provider attitudes precluding prevention delivery.
      Intervention strategies can help clinicians more consistently deliver behavioral
      prevention messages to their HIV-infected patients.

PMID- 22970976
TI  - A new flavanocoumarin from the root of Flemingia philippinensis.
AB  - One new flavanocoumarin, flemicoumarin A (1) was isolated from the EtOAc-soluble
      partition of the root of Flemingia philippinensis, along with three known
      compounds, namely 4,2'-epoxy-4',5-dihydroxy-7,5'-dimethoxy-3-phenylcoumarin (2),
      kaempferol 6-C-glucoside (3) and dracocephaloside (4). The structure of compound
      1 was elucidated on the basis of its 1D, 2D NMR, CD and MS data. The structures
      of the known compounds were identified by comparison of their spectroscopic data
      with those reported in the literature. Compounds 1-4 exhibited inactivity against
      MCF-7, A549 and Hep-G2 human cancer cell lines in vitro by MTT colorimetric
      assay.

PMID- 22970978
TI  - Extramedullary plasmacytoma of the eyelid: a case report and review of
      literature.
AB  - Primary extramedullary plasmacytomas of the eyelid are rare with only five other
      cases reported in the literature. A 43-year-old Chinese man presented with
      painless swelling of the left lower eyelid that developed over the past two
      years. An incisional biopsy and histopathological analysis of the lesion revealed
      a primary extramedullary plasmacytoma of the eyelid. The tumour was completely
      excised. There has been no tumour recurrence over the last five years. This
      tumour should be among those considered when encountering an atypical adnexal
      lesion. A systemic examination, relevant clinical investigations, as well as life
      long monitoring are essential for these patients due to the strong association of
      extramedullary plasmacytoma with multiple myeloma. When a lesion can be
      completely resected, surgery provides similar results to radiotherapy.

PMID- 22970977
TI  - Rosuvastatin-attenuated heart failure in aged spontaneously hypertensive rats via
      PKCalpha/beta2 signal pathway.
AB  - There are controversies concerning the capacity of Rosuvastatin to attenuate
      heart failure in end-stage hypertension. The aim of the study was to show whether
      the Rosuvastatin might be effective or not for the heart failure treatment.
      Twenty-one spontaneously hypertensive rats (SHRs) aged 52 weeks with heart
      failure were randomly divided into three groups: two receiving Rosuvastatin at 20
      and 40 mg/kg/day, respectively, and the third, placebo for comparison with seven
      Wistar-Kyoto rats (WKYs) as controls. After an 8-week treatment, the systolic
      blood pressure (SBP) and echocardiographic features were evaluated; mRNA level of
      B-type natriuretic peptide (BNP) and plasma NT-proBNP concentration were
      measured; the heart tissues were observed under electron microscope (EM);
      myocardial sarcoplasmic reticulum Ca(2+) pump (SERCA-2) activity and mitochondria
      cytochrome C oxidase (CCO) activity were measured; the expressions of SERCA-2a,
      phospholamban (PLB), ryanodine receptor2 (RyR2), sodium-calcium exchanger 1
      (NCX1), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein
      phosphatase inhibitor-1 (PPI-1) were detected by Western blot and RT-qPCR; and
      the total and phosphorylation of protein kinase Calpha/beta (PKCalpha/beta) were
      measured. Aged SHRs with heart failure was characterized by significantly
      decreased left ventricular ejection fraction and left ventricular fraction
      shortening, enhanced left ventricular end-diastolic diameter and LV Volume,
      accompanied by increased plasma NT-proBNP and elevated BNP gene expression.
      Damaged myofibrils, vacuolated mitochondria and swollen sarcoplasmic reticulum
      were observed by EM. Myocardium mitochondria CCO and SERCA-2 activity decreased.
      The expressions of PLB and NCX1 increased significantly with up-regulation of PPI
      1 and down-regulation of CaMKII, whereas that of RyR2 decreased. Rosuvastatin was
      found to ameliorate the heart failure in aged SHRs and to improve changes in
      SERCA-2a, PLB, RyR2, NCX1, CaMKII and PPI-1; PKCalpha/beta2 signal pathway to be
      suppressed; the protective effect of Rosuvastatin to be dose dependent. In
      conclusion, the heart failure of aged SHRs that was developed during the end
      stage of hypertension could be ameliorated by Rosuvastatin.

PMID- 22970979
TI  - Total syntheses of HMP-Y1, hibarimicinone, and HMP-P1.
AB  - Total syntheses of HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone,
      and HMP-P1 are described using a two-directional synthesis strategy. A novel
      benzyl fluoride Michael-Claisen reaction sequence was developed to construct the
      complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical, two
      directional, double annulation. Through efforts to convert HMP-Y1 derivatives to
      hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected
      HMP-Y1 was realized. A two-directional unsymmetrical double annulation and
      biomimetic etherification was developed to construct the polycyclic and highly
      oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. The use of
      a racemic biaryl precursor allowed for the synthesis of both hibarimicinone
      atropisomers and provides the first confirmation of the structure of atrop
      hibarimicinone. Additionally, this work documents the first reported full
      characterization of atrop-hibarimicinone, HMP-Y1, atrop-HMP-Y1, and HMP-P1. Last,
      a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was
      discovered, which provides valuable information necessary to achieve syntheses of
      the glycosylated congeners of hibarimicinone.

PMID- 22970980
TI  - Identification of ROS produced by photodynamic activity of
      chlorophyll/cyclodextrin inclusion complexes.
AB  - Photodynamic therapy (PDT) is a way of treating malignant tumors and
      hyperproliferative diseases. It is based on the use of photosensitizer, herein
      the chlorophyll a (chl a), and a light of an appropriate wavelength. The
      interaction of the photosensitizer (PS) with the light produces reactive oxygen
      species (ROS), powerful oxidizing agents, which cause critical damage to the
      tissue. To solubilize chl a in aqueous solution and to obtain it as monomer, we
      have used cyclodextrins, carriers which are able to interact with the pigment and
      form the inclusion complex. The aim of this study is to examine which types of
      ROS are formed by Chl a/cyclodextrin complexes in phosphate buffered solution and
      cell culture medium, using specific molecules, called primary acceptors, which
      react selectively with the reactive species. In fact the changes of the
      absorption and the emission spectra of these molecules after the illumination of
      the PS provide information on the specific ROS formation. The (1) O2 formation
      has been tested using chemical methods based on the use of Uric Acid (UA), 9,10
      diphenilanthracene (DPA) and Singlet oxygen sensor green (SOSG) and by direct
      detection of Singlet Oxygen ((1) O2 ) luminescence decay at 1270 nm. Moreover,
      2,7-dichlorofluorescin and ferricytochrome c (Cyt Fe(3+) ) have been used to
      detect the formation of hydrogen peroxide and superoxide radical anion, which
      reduces Fe(3+) of the ferricytochrome to Fe(2+) , respectively.

PMID- 22970981
TI  - Multi-Matrix System (MMX(r)) mesalamine for the treatment of mild-to-moderate
      ulcerative colitis.
AB  - INTRODUCTION: Ulcerative colitis (UC) is an inflammatory disease of the colon
      characterized by periods of active disease and remission. The pathogenesis of
      this disease is likely a complex interaction of genetic predisposition,
      environmental factors, and immune system dysregulation, and is not completely
      understood. A Multi-MatriX (MMX(r)) system formulation of mesalamine, MMX
      mesalamine (SPD476; Lialda(r); Mesavancol(r); Mezavant(r)), allows for high-dose,
      once-daily dosing for patients with mild-to-moderate UC. Mesalamine is a
      topically active agent with anti-inflammatory properties. AREAS COVERED:
      Available literature regarding MMX mesalamine is extensively reviewed in this
      article, covering its chemical makeup, mechanism of action, pharmaceutics and
      pharmacokinetics, clinical efficacy, and safety and tolerability. EXPERT OPINION:
      A dose of 2.4 and 4.8 g was used in large Phase III clinical trials and was
      efficacious for induction of clinical and endoscopic remission in UC. MMX
      mesalamine was also efficacious in large multicenter maintenance studies for the
      maintenance of clinical and endoscopic remission. The introduction of the first
      once-daily mesalamine has given practitioners and patients more flexibility in
      dosing administration, which will ultimately lead to higher satisfaction and
      improved clinical outcomes.

PMID- 22970982
TI  - Use of digital retinal imaging in screening for retinopathy of prematurity.
AB  - The frequency of premature births is increasing world-wide. This factor, combined
      with improved survival and revised screening criteria, is resulting in an
      increased workload in screening for retinopathy of prematurity. Digital retinal
      imaging is emerging as an important alternative tool for diagnosing retinopathy
      of prematurity, and its use has even been extended to developing countries.
      Neonatal nurses and technicians can be trained to use digital imaging devices
      effectively. This is important in areas that do not have ready access to
      paediatric ophthalmologists. The ability to transfer images electronically makes
      it a valuable tool in telemedicine, while the ability to store and retrieve
      images is also advantageous from a medico-legal perspective. Image analysis
      software can further improve the accuracy of diagnosis. The main limitation of
      this technology is its high capital cost.

PMID- 22970983
TI  - Prevalence and genotypic relatedness of carbapenem resistance among multidrug
      resistant P. aeruginosa in tertiary hospitals across Thailand.
AB  - BACKGROUND: Increased infection caused by multidrug resistant (MDR) Pseudomonas
      aeruginosa has raised awareness of the resistance situation worldwide. Carbapenem
      resistance among MDR (CR-MDR) P. aeruginosa has become a serious life-threatening
      problem due to the limited therapeutic options. Therefore, the objectives of this
      study were to determine the prevalence, the antibiotic susceptibility patterns
      and the relatedness of CR-MDR P. aeruginosa in tertiary hospitals across
      Thailand. METHODS: MDR P. aeruginosa from eight tertiary hospitals across
      Thailand were collected from 2007-2009. Susceptibility of P. aeruginosa clinical
      isolates was determined according to the Clinical and Laboratory Standards
      Institute guideline. Selected CR-MDR P. aeruginosa isolates were genetically
      analyzed by pulsed-field gel electrophoresis. RESULTS: About 261 clinical
      isolates were identified as MDR P. aeruginosa and approximately 71.65% were found
      to be CR-MDR P. aeruginosa. The result showed that the meropenem resistance rate
      was the highest reaching over 50% in every hospitals. Additionally, the type of
      hospitals was a major factor affecting the resistance rate, as demonstrated by
      significantly higher CR-MDR rates among university and regional hospitals. The
      fingerprinting map identified 107 clones with at least 95% similarity. Only 4
      clones were detected in more than one hospital. CONCLUSIONS: Although the
      antibiotic resistance rate was high, the spreading of CR-MDR was found locally.
      Specific strains of CR-MDR did not commonly spread from one hospital to another.
      Importantly, clonal dissemination ratio indicated limited intra-hospital
      transmission in Thailand.

PMID- 22970985
TI  - Fluctuations of MS births and UV-light exposure.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in
      spring when compared to autumn. Fluctuation of UV-light has been hypothesized to
      drive this phenomenon. AIM: To assess the correlation between fluctuation of
      sunlight and birth season in persons with MS. METHODS: For this record-linkage
      study, we collected from the international MSBase and the Italian MS iMed-web
      databases the dates of birth of 11,415 patients with MS from 36 centres from 15
      countries worldwide and compared these to dates of live-births from national
      registries. From all participating sites, we collected data on UV-light
      fluctuation and assessed its correlation with seasonal fluctuation in MS births.
      RESULTS: Compared with the reference cohort, an increased proportion of persons
      with MS were born in spring and a decreased proportion in autumn (odds ratio (OR)
      to be born in spring versus autumn = 1.158, chi2 = 36.347, P < 0.001). There was
      no significantly increased fluctuation of MS births with increased quartile of
      ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation
      of MS births as found in this worldwide cohort of patients with MS did not
      correlate with variation in seasonal fluctuation of UV-light. Most likely, it
      results from a complex interplay between fluctuation of sunlight, behavioural
      factors, other environmental factors and (epi)genetic factors.

PMID- 22970986
TI  - White matter pathology--an endophenotype for bipolar disorder?
AB  - BACKGROUND: Neuroimaging investigations of white matter abnormalities in subjects
      at genetic risk for bipolar disorders (BD) potentially predating the onset of BD
      offer several advantages. They are not confounded by the presence of illness
      duration or previous treatment with medication and may ultimately inform
      evaluation of risk for subsequent development of BD and subsequent therapeutic
      intervention. DISCUSSION: Although a number of imaging studies in subjects at
      genetic risk for BD are available the results are conflicting and no reliable
      structural markers of genetic liability to bipolar disorders have been proposed.
      We debate that white matter pathology may be central to the genetic risk to
      develop BD. Thus, white matter abnormalities detectable in HR subjects but not in
      controls may reflect genetically driven trait markers. Similar abnormalities may
      be also evident both in the HR and in BD, suggesting the possibility of genetic
      risk factors shared by both groups. Conversely, white matter alterations observed
      in BD patients but not in HR and controls can be interpreted as state markers.
      SUMMARY: We suggest that white matter alterations may represent endophenotypes
      and neurobiological markers intermediate between the underlying susceptibility
      genes and the clinical expression of BD.

PMID- 22970987
TI  - Characterization and quantitative analysis of single-walled carbon nanotubes in
      the aquatic environment using near-infrared fluorescence spectroscopy.
AB  - Near infrared fluorescence (NIRF) spectroscopy is capable of sensitive and
      selective detection of semiconductive, single-walled carbon nanotubes (SWNT)
      using the unique electronic bandgap properties of these carbon allotropes. We
      reported here the first detection and quantitation of SWNT in sediment and biota
      at environmentally relevant concentrations using NIRF spectroscopy. In addition,
      we utilized this technique to qualitatively characterize SWNT samples before and
      after ecotoxicity, bioavailability and fate studies in the aquatic environment.
      Sample preparation prior to NIRF analysis consisted of surfactant-assisted high
      power ultrasonication. The bile salt sodium deoxycholate (SDC) enabled efficient
      extraction and disaggregation of SWNT prior to NIRF analysis. The method was
      validated using standard-addition experiments in two types of estuarine
      sediments, yielding recoveries between 66 +/- 7% and 103 +/- 10% depending on
      SWNT type and coating used, demonstrating the ability to isolate SWNT from
      complex sediment matrices. Instrument detection limits were determined to be 15
      ng mL(-1) SWNT in 2% SDC solution and method detection limits (including a
      concentration step) were 62 ng g(-1) for estuarine sediment, and 1.0 MUg L(-1)
      for water. Our work has shown that NIRF spectroscopy is highly sensitive and
      selective for SWNT and that this technique can be applied to track the
      environmental and biological fate of this important class of carbon nanomaterial
      in the aquatic environment.

PMID- 22970988
TI  - Postoperative phosphodiesterase type 5 inhibitor administration increases the
      rate of urinary continence recovery after bilateral nerve-sparing radical
      prostatectomy.
AB  - OBJECTIVES: To investigate the effect of phosphodiesterase type 5 inhibitor on
      urinary continence recovery after bilateral nerve-sparing radical prostatectomy.
      METHODS: We analyzed data of 393 open bilateral nerve-sparing radical
      prostatectomies carried out between 2005 and 2010. Patients who recovered urinary
      continence within the first month after catheter removal (n = 52) were excluded.
      This resulted in 341 evaluable patients. Urinary continence recovery was defined
      as being completely pad free over a period of 24 h. Patients were stratified
      according to postoperative daily (n = 58; 17%), on-demand (n = 112; 32.8%) and no
      (n = 171; 50.1%) phosphodiesterase type 5 inhibitor use. The effect of
      phosphodiesterase type 5 inhibitor use on urinary continence was assessed using
      the Kaplan-Meier method. Uni- and multivariable Cox regression analyses were used
      to test the association between phosphodiesterase type 5 inhibitor and urinary
      continence recovery after adjusting for cofounders. RESULTS: At a mean follow up
      of 36.4 months after surgery (median: 33), 288 patients (84.5%) recovered urinary
      continence after bilateral nerve-sparing radical prostatectomy. Patients who did
      not use phosphodiesterase type 5 inhibitor after surgery had lower rates of
      urinary continence recovery at 1- and 2-year follow up as compared with patients
      taking phosphodiesterase type 5 inhibitor (67.1 vs 86.7% and 76 vs 94.4%,
      respectively; P < 0.001). After adjusting for all confounders, multivariable
      analysis showed that phosphodiesterase type 5 inhibitor use, either on demand or
      daily, had a positive impact on urinary continence recovery (P = 0.03).
      CONCLUSIONS: Patients taking phosphodiesterase type 5 inhibitor have higher
      urinary continence recovery rates as compared with patients left untreated after
      bilateral nerve-sparing radical prostatectomy. An improvement in sphincteric and
      pelvic floor blood supply might be responsible for this beneficial effect
      associated with the use of phosphodiesterase type 5 inhibitor.

PMID- 22970989
TI  - Intracellular delivery of DNA and enzyme in active form using degradable
      carbohydrate-based nanogels.
AB  - The facile encapsulation of biomolecules along with efficient formulation and
      storage makes nanogels ideal candidates for drug and gene delivery. So far,
      nanogels have not been used for the codelivery of plasmid DNA and proteins due to
      several limitations, including low encapsulation efficacy of biomolecule of
      similar charges and the size of cargo materials. In this study, temperature and
      pH sensitive carbohydrate-based nanogels are synthesized via reversible addition
      fragmentation chain transfer (RAFT) polymerization technique and are studied in
      detail for their capacity to encapsulate and codeliver plasmid DNA and proteins.
      The temperature sensitive property of nanogels allows the facile encapsulation of
      biomaterials, while its acid-degradable profile allows the burst release of
      biomolecules in endosomes. Hence these materials are expected to serve as
      efficient vectors to deliver biomolecules of choice either alone or as codelivery
      system. The nanogels produced are relatively monodisperse and are around 30-40 nm
      in diameter at 37  degrees C. DNA condensation efficacy of the nanogels is
      dependent on the hydrophobic property of the core of the nanogels. The DNA
      nanogel complexes are formed by the interaction of carbohydrate residues of
      nanogels with the DNA, and complexes are further stabilized with linear cationic
      glycopolymers. The DNA-nanogels complexes are also studied for their protein
      loading capacity. The degradation of the nanogels and the controlled release of
      DNA and proteins are then studied in vitro. Furthermore, the addition of a
      nontoxic, cationic glycopolymer to the nanogel-DNA complexes is found to improve
      the cellular uptake and hence to improve gene expression.

PMID- 22970991
TI  - Low-sample flow secondary electrospray ionization: improving vapor ionization
      efficiency.
AB  - In secondary electrospray ionization (SESI) systems, gaseous analytes exposed to
      an elecrospray plume become ionized after charge is transferred from the charging
      electrosprayed particles to the sample species. Current SESI systems have shown a
      certain potential. However, their ionization efficiency is limited by space
      charge repulsion and by the high sample flows required to prevent vapor dilution.
      As a result, they have a poor conversion ratio of vapor into ions. We have
      developed and tested a new SESI configuration, termed low-flow SESI, that permits
      the reduction of the required sample flows. Although the ion to vapor
      concentration ratio is limited, the ionic flow to sample vapor flow ratio
      theoretically is not. The new ionizer is coupled to a planar differential
      mobility analyzer (DMA) and requires only 0.2 lpm of vapor sample flow to produce
      3.5 lpm of ionic flow. The achieved ionization efficiency is 1/700 (one ion for
      every 700 molecules) for TNT and, thus, compared with previous SESI ionizers
      coupled with atmospheric pressure ionization-mass spectrometry (API-MS)
      (Mesonero, E.; Sillero, J. A.; Hernandez, M.; Fernandez de la Mora, J.
      Philadelphia PA, 2009) has been improved by a large factor of at least 50-100
      (our measurements indicate 70). The new ionizer coupled with the planar DMA and a
      triple quadrupole mass spectrometer (ABSciex API5000) requires only 20 fg (50
      million molecules) to produce a discernible signal after mobility and MS(2)
      analysis.

PMID- 22970990
TI  - Chemical proteomics-based analysis of off-target binding profiles for
      rosiglitazone and pioglitazone: clues for assessing potential for cardiotoxicity.
AB  - Drugs exert desired and undesired effects based on their binding interactions
      with protein target(s) and off-target(s), providing evidence for drug efficacy
      and toxicity. Pioglitazone and rosiglitazone possess a common functional core,
      glitazone, which is considered a privileged scaffold upon which to build a drug
      selective for a given target--in this case, PPARgamma. Herein, we report a
      retrospective analysis of two variants of the glitazone scaffold, pioglitazone
      and rosiglitazone, in an effort to identify off-target binding events in the rat
      heart to explain recently reported cardiovascular risk associated with these
      drugs. Our results suggest that glitazone has affinity for dehydrogenases,
      consistent with known binding preferences for related rhodanine cores. Both drugs
      bound ion channels and modulators, with implications in congestive heart failure,
      arrhythmia, and peripheral edema. Additional proteins involved in glucose
      homeostasis, synaptic transduction, and mitochondrial energy production were
      detected and potentially contribute to drug efficacy and cardiotoxicity.

PMID- 22970992
TI  - Synchrotron-based far-infrared spectroscopic investigation and ab initio
      calculations of 3-oxetanone: observation and analysis of the nu7 band and the
      Coriolis coupled nu16 and nu20 bands.
AB  - Rotationally resolved vibrational spectra of the four-membered heterocycle 3
      oxetanone (c-C(3)H(4)O(2)) have been investigated in the 360-720 cm(-1) region
      with a resolution of 0.000 959 cm(-1) using synchrotron radiation from the
      Canadian Light Source. The observed bands correspond to motions best described as
      C?O deformation out-of-plane (nu(20)) at 399.6 cm(-1), C?O deformation in-plane
      (nu(16)) at 448.2 cm(-1), and the ring deformation (nu(7)) at 685.0 cm(-1).
      Infrared ground state combination differences along with previously reported pure
      rotational transitions were used to obtain the ground state spectroscopic
      parameters. Band centers, rotational and centrifugal distortion constants for the
      nu(7), nu(16), and nu(20) vibrational excited states were accurately determined
      by fitting a total of 10,319 assigned rovibrational transitions in a global
      analysis. The two adjacent carbonyl deformation bands, nu(16) and nu(20), were
      found to be mutually perturbed through a first-order a-type Coriolis interaction
      which was accounted for in the multiband analysis. The band centers agree within
      3% of the ab initio estimates using DFT theory.

PMID- 22970993
TI  - Does sex affect the outcome of laparoscopic cholecystectomy? A retrospective
      analysis of single center experience.
AB  - INTRODUCTION: The aim of our study was to determine the effect of sex on the
      outcome of laparoscopic cholecystectomy in terms of operative time, conversion to
      open cholecystectomy, postoperative complications and mean hospital stay.
      METHODS: In this retrospective observational study, we analyzed the medical
      records of 2061 patients who underwent laparoscopic cholecystectomy in the
      surgical department of Khyber Teaching Hospital (Peshawar, Pakistan) between
      March 2008 and January 2010. chi(2)  test and t-test were respectively used to
      analyze categorical and numerical variables. P <= 0.05 was considered
      significant. RESULTS: The study included 1772 female and 289 male patients. The
      mean age for male patients was 44.07 +/- 11.91 years compared to 41.29 +/- 12.18
      years for female patients (P = 0.706). Laparoscopic cholecystectomy was
      successfully completed in 1996 patients. The conversion rate was higher in men (P
      < 0.001), and the mean operating time was longer in men (P < 0.001). Bile duct
      injuries occurred more frequently in men (P < 0.001). Gallbladder perforation and
      gallstone spillage also occurred more commonly in men (P = 0.001); similarly
      severe inflammation was reported more in male patients (P = 0001). There were no
      statistically significant differences in mean hospital stay, wound infection and
      port-site herniation between men and women. Multivariate regression analysis
      showed that the male sex is an independent risk factor for conversion to open
      cholecystectomy (odds ratio = 2.65, 95% confidence interval: 1.03-6.94, P =
      0.041) and biliary injuries (odds ratio = 0.95, 95% confidence interval: 0.91
      0.99, P-value = 0.036). CONCLUSIONS: Laparoscopic cholecystectomy is often
      challenging in men on account of more adhesions and inflammation. This leads to
      higher conversion rates and more postoperative complications. Optimized planning
      and a more experienced operating surgeon may help overcome these problems.

PMID- 22970994
TI  - Intralesional steroid injection: an alternative treatment option for vocal
      process granuloma in ten patients.

PMID- 22970995
TI  - History of the Dental Trauma Guide.
AB  - The history of the Dental Trauma Guide dates back to 1965, where guidelines were
      developed for trauma records and treatment of various trauma entities at the
      Department of Oral and Maxillofacial Surgery at the University Hospital in
      Copenhagen. In 1972, a unique possibility came up at the Serum Institute in
      Copenhagen to test various dental trauma procedures in monkeys, which served as
      kidney donors in the polio vaccine production. Over the years, 40 000 dental
      trauma patients were treated at the Trauma Centre according to established
      guidelines, and 4000 of these have been enrolled in long-term follow-up of
      various trauma entities. This has resulted in 79 clinical studies, and 64 studies
      in monkeys have examined the effect of various treatment procedures and the
      aetiology of most healing complications.

PMID- 22970996
TI  - Domestic chores workload and depressive symptoms among children affected by
      HIV/AIDS in China.
AB  - Limited data are available regarding the effects of domestic chores workload on
      psychological problems among children affected by HIV/AIDS in China. The current
      study aims to examine association between children's depressive symptoms and the
      domestic chores workload (i.e., the frequency and the amount of time doing
      domestic chores). Data were derived from the baseline survey of a longitudinal
      study which investigated the impact of parental HIV/AIDS on psychological
      problems of children. A total of 1449 children in family-based care were included
      in the analysis: 579 orphaned children who lost one or both parents due to AIDS,
      466 vulnerable children living with one or both parents being infected with HIV,
      and 404 comparison children who did not have HIV/AIDS-infected family members in
      their families. Results showed differences on domestic chores workload between
      children affected by HIV/AIDS (orphans and vulnerable children) and the
      comparison children. Children affected by HIV/AIDS worked more frequently and
      worked longer time on domestic chores than the comparison children. Multivariate
      linear regression analysis showed that domestic chores workload was positively
      associated with depressive symptoms. The data suggest that children affected by
      HIV/AIDS may face increasing burden of domestic chores and it is necessary to
      reduce the excessive workload of domestic chores among children affected by
      HIV/AIDS through increasing community-based social support for children in the
      families affected by HIV/AIDS.

PMID- 22970997
TI  - Co-occurring development of early childhood communication and motor skills:
      results from a population-based longitudinal study.
AB  - BACKGROUND: Communicative and motor development is frequently found to be
      associated. In the current study we investigate to what extent communication and
      motor skills at 11/2 years predict skills in the same domains at 3 years of age.
      METHODS: This study is based on the Norwegian Mother and Child Cohort Study
      (MoBa) conducted by the Norwegian Institute of Public Heath. Data stem from
      62,944 children and their mothers. Mothers completed questionnaires on their
      child's communication and motor skills at ages 11/2 and 3. Associations between
      communication and motor skills were estimated in a cross-lagged model with latent
      variables. RESULTS: Early communication skills were correlated with early motor
      skills (0.72). Stability was high (0.81) across time points for motor skills and
      somewhat lower (0.40) for communication skills. Early motor skills predicted
      later communication skills (0.38) whereas early communication skills negatively
      predicted later motor skills (-0.14). CONCLUSION: Our findings provide support
      for the hypothesis that these two difficulties are not symptoms of separate
      disorders, but might rather be different manifestations of a common underlying
      neurodevelopmental weakness. However, there also seem to be specific
      developmental pathways for each domain. Besides theoretical interest, more
      knowledge about the relationship between these early skills might shed light upon
      early intervention strategies and preventive efforts commonly used with children
      with problems in these areas. Our findings suggest that the relationship between
      language and motor skills is not likely to be simple and directional but rather
      to be complex and multifaceted.

PMID- 22970998
TI  - Bone flap resorption: risk factors for the development of a long-term
      complication following cranioplasty after decompressive craniectomy.
AB  - Aseptic bone flap resorption (BFR) is a known long-term complication after
      cranioplasty (CP). We analyzed our institutional data in order to identify risk
      factors for BFR. From October 1999 to April 2012, 254 patients underwent CP after
      decompressive craniectomy (DC) at our institution, and had a long-term follow-up
      period of >1 year after CP (range 12-146 months). Overall, BFR occurred in 10 of
      254 patients as a long-term complication after CP (4%). BFR developed more often
      in patients aged <=18 years (p=0.008), in patients who previously underwent DC
      for traumatic brain injury (p=0.04), and in patients with multiple fractures
      within the reinserted bone flap (p=0.002). Furthermore, BFR developed
      significantly more often in patients who underwent cranioplasty <=2 months after
      DC (p=0.008), as well as in patients with wound healing disturbance or abscess as
      an early complication after the CP procedure (p=0.01). The multivariate analysis
      of the present data identified the presence of multiple fractures within the bone
      flap (p=0.002, OR 10.3, 95% CI 2.4-43.8), wound infection after CP (p=0.003, OR
      12.3, 95% CI 2.3-65.3), and cranioplasty performed <=2 months after DC (p=0.01,
      OR 6.3, 95% CI 1.5-26.3) as independent risk factors for the development of BFR
      after CP in a large series with long-term follow-up. This might influence future
      surgical decision making, especially in patients fulfilling high risk criteria
      for developing BFR.

PMID- 22970999
TI  - Decaying mouse volatiles perceived by Calliphora vicina Rob.-Desv.
AB  - Volatiles emitted by decaying human remains are in the focus of recent research.
      The identification of core volatiles in this field is of high importance, because
      cadaveric volatiles generally show high variation. In this study, the volatile
      profiles of five mice (Myodes glareolus) were sampled with charcoal filter tubes
      from their time of death until advanced decay. Eleven compounds were quantitated
      by means of gas chromatography-mass spectrometry. Electroantennographic
      experiments with female Calliphora vicina antennae led to the identification of
      dimethyl trisulfide, dimethyl disulfide, nonanal, hexan-1-ol, 1-octen-3-ol, 3
      methylbutan-1-ol, and heptanal as electrophysiologically active compounds. When
      these were compared, dimethyl trisulfide (17 ng/MUL) and dimethyl disulfide (11
      ng/MUL) were found to be emitted in higher concentrations. The roles of these
      compounds and nonanal as core volatiles for cadaver detection or postmortem time
      determination and their correlation to the stages of decay and the accumulated
      degree days are discussed.

PMID- 22971000
TI  - Temperature-responsive one-dimensional nanogels formed by the cross-linker-aided
      single particle nanofabrication technique.
AB  - A single particle nanofabrication technique was successfully applied to the
      fabrication of homogeneous poly(N-isopropylacrylamide) (PNIPAAm) 1D nanogels over
      a large area, using N,N'-methylene-bis-acrylamide (MBAAm) as a cross-linker. The
      PNIPAAm 1D nanogels with high aspect ratio over 130 were formed uniformly on the
      substrate, and the mechanical strength and the length of the 1D nanogels can be
      easily controlled by adjusting the MBAAm content. The 1D nanogels were
      transformed from the non-aggregated to aggregated forms over a lower critical
      solution temperature (LCST) of approximately 32  degrees C in water. Precise
      trace of the temperature induced change in the size of the 1D nanogel was well
      interpreted by the coil-to-globule transition of PNIPAAm, which was clearly
      visualized in the present study. This is the first report of uniform shape change
      for a 1D nanogel by external stimulus over a large area.

PMID- 22971001
TI  - Catalysis through temporary intramolecularity: mechanistic investigations on
      aldehyde-catalyzed Cope-type hydroamination lead to the discovery of a more
      efficient tethering catalyst.
AB  - Mechanistic investigations on the aldehyde-catalyzed intermolecular
      hydroamination of allylic amines using N-alkylhydroxylamines are presented. Under
      the reaction conditions, the presence of a specific aldehyde catalyst allows
      formation of a mixed aminal intermediate, which permits intramolecular Cope-type
      hydroamination. The reaction was determined to be first-order in both the
      aldehyde catalyst (alpha-benzyloxyacetaldehyde) and the allylic amine. However,
      the reaction displays an inverse order behavior in benzylhydroxylamine, which
      reveals a significant off-cycle pathway and highlights the importance of an
      aldehyde catalyst that promotes a reversible aminal formation. Kinetic isotope
      effect experiments suggest that hydroamination is the rate-limiting step of this
      catalytic cycle. Overall, these results enabled the elaboration of a more
      accurate catalytic cycle and led to the development of a more efficient catalytic
      system for alkene hydroamination. The use of 5-10 mol % of paraformaldehyde
      proved more effective than the use of 20 mol % of alpha-benzyloxyacetaldehyde,
      leading to high yields of intermolecular hydroamination products within 24 h at
      30  degrees C.

PMID- 22971002
TI  - Characterization and diagnosis of cancer by native fluorescence spectroscopy of
      human urine.
AB  - Urine is one of the diagnostically important bio fluids, as it has different
      metabolites in it, where many of them are native fluorophores. Native
      fluorescence characteristics of human urine samples were studied using excitation
      emission matrices (EEMs) over a range of excitation and emission wavelengths, and
      emission spectra at 405 nm excitation, to discriminate patients with cancer from
      the normal subjects. The fluorescence spectra of urine samples of cancer patients
      exhibit considerable spectral differences in both EEMs and emission spectra with
      respect to normal subjects. Different ratios were calculated using the
      fluorescence intensity values of the emission spectra and they were used as input
      variables for a multiple linear discriminant analysis across different groups.
      The discriminant analysis classifies 94.7% of the original grouped cases and
      94.1% of the cross-validated grouped cases correctly. Based on the fluorescence
      emission characteristics of urine and statistical analysis, it may be concluded
      that the fluorophores nicotinamide adenine dinucleotide (NADH) and flavins may be
      considered as metabolomic markers of cancer.

PMID- 22971003
TI  - Late-phase investigational approaches for the treatment of relapsed/refractory
      acute myeloid leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is a malignant hematologic disorder
      that affects more than 13,000 adults each year in the USA. Despite continued
      advances in the understanding of the molecular pathogenesis of the disease and
      patient management, the cure rate for AML remains relatively low, largely due to
      a high rate of relapsed or refractory disease. AREAS COVERED: The purpose of this
      review is to provide an understanding of the unmet needs in relapsed/refractory
      AML, and to assess promising investigational agents with ongoing or planned Phase
      III clinical trials. EXPERT OPINION: Although the treatment of
      relapsed/refractory AML remains a challenge, numerous new chemotherapeutics are
      currently in development. Enrollment in clinical trials should be strongly
      considered for patients with relapsed/refractory disease, and emerging data may
      help identify new agents with significant activity in this setting.

PMID- 22971004
TI  - Early identification of autism: a comparison of the Checklist for Autism in
      Toddlers and the Modified Checklist for Autism in Toddlers.
AB  - There is still debate as to what is the most effective strategy for identifying
      the early signs of autism in very young children. Two levels of screening having
      been advocated: broad-based developmental surveillance and targeted screening.
      Two popular tools for use in developmental surveillance are the Checklist for
      Autism in Toddlers (CHAT) and the Modified Checklist for Autism in Toddlers (M
      CHAT). The purpose of this article is to summarise the current evidence for
      screening for autistic symptoms in very young children using CHAT and M-CHAT. A
      systematic search was carried out of electronic database and other sources for
      original studies which evaluated the use of CHAT and M-CHAT in screening for
      autism in children younger than 5 years of age. Studies were included for review
      if they evaluated the sensitivity and/or specificity of CHAT or M-CHAT, or
      described the best age to administer these instruments. The available evidence
      suggests that characteristic behaviours in autism should be evident in simple
      forms before the age of 18 months, while screening at 24 months should be
      conducted to identify those who regress. Administering a screening tool during 18
      to 24-month well-child visits improves early identification of autism, while the
      stability of diagnosis at the ages of 18 months and 24 months is confirmed. M
      CHAT has slightly better sensitivity and specificity compared to CHAT, and is
      preferable to use as a developmental surveillance screening instrument.

PMID- 22971006
TI  - Sequential depletion of human serum for the search of osteoarthritis biomarkers.
AB  - BACKGROUND: The field of biomarker discovery, development and application has
      been the subject of intense interest and activity, especially with the recent
      emergence of new technologies, such as proteomics-based approaches. In
      proteomics, search for biomarkers in biological fluids such as human serum is a
      challenging issue, mainly due to the high dynamic range of proteins present in
      these types of samples. Methods for reducing the content of most highly abundant
      proteins have been developed, including immunodepletion or protein equalization.
      In this work, we report for the first time the combination of a chemical
      sequential depletion method based in two protein precipitations with acetonitrile
      and DTT, with a subsequent two-dimensional difference in-gel electrophoresis (2D
      DIGE) analysis for the search of osteoarthritis (OA) biomarkers in human serum.
      The depletion method proposed is non-expensive, of easy implementation and allows
      fast sample throughput. RESULTS: Following this workflow, we have compared sample
      pools of human serum obtained from 20 OA patients and 20 healthy controls. The
      DIGE study led to the identification of 16 protein forms (corresponding to 14
      different proteins) that were significantly (p < 0.05) altered in OA when
      compared to controls (8 increased and 7 decreased). Immunoblot analyses confirmed
      for the first time the increase of an isoform of Haptoglobin beta chain (HPT) in
      sera from OA patients. CONCLUSIONS: Altogether, these data demonstrate the
      utility of the proposed chemical sequential depletion for the analysis of sera in
      protein biomarker discovery approaches, exhibit the usefulness of quantitative 2D
      gel-based strategies for the characterization of disease-specific patterns of
      protein modifications, and also provide a list of OA biomarker candidates for
      validation.

PMID- 22971005
TI  - Dissecting the role of human embryonic stem cell-derived mesenchymal cells in
      human umbilical vein endothelial cell network stabilization in three-dimensional
      environments.
AB  - The microvasculature is principally composed of two cell types: endothelium and
      mural support cells. Multiple sources are available for human endothelial cells
      (ECs) but sources for human microvascular mural cells (MCs) are limited. We
      derived multipotent mesenchymal progenitor cells from human embryonic stem cells
      (hES-MC) that can function as an MC and stabilize human EC networks in three
      dimensional (3D) collagen-fibronectin culture by paracrine mechanisms. Here, we
      have investigated the basis for hES-MC-mediated stabilization and identified the
      pleiotropic growth factor hepatocyte growth factor/scatter factor (HGF/SF) as a
      putative hES-MC-derived regulator of EC network stabilization in 3D in vitro
      culture. Pharmacological inhibition of the HGF receptor (Met) (1 MUm SU11274)
      inhibits EC network formation in the presence of hES-MC. hES-MC produce and
      release HGF while human umbilical vein endothelial cells (HUVEC) do not. When
      HUVEC are cultured alone the networks collapse, but in the presence of
      recombinant human HGF or conditioned media from human HGF-transduced cells
      significantly more networks persist. In addition, HUVEC transduced to
      constitutively express human HGF also form stable networks by autocrine
      mechanisms. By enzyme-linked immunosorbent assay, the coculture media were
      enriched in both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2), but at
      significantly different levels (Ang1=159+/-15 pg/mL vs. Ang2=30,867+/-2685 pg/mL)
      contributed by hES-MC and HUVEC, respectively. Although the coculture cells
      formed stabile network architectures, their morphology suggests the assembly of
      an immature plexus. When HUVEC and hES-MC were implanted subcutaneously in immune
      compromised Rag1 mice, hES-MC increased their contact with HUVEC along the axis
      of the vessel. This data suggests that HUVEC and hES-MC form an immature plexus
      mediated in part by HGF and angiopoietins that is capable of maturation under the
      correct environmental conditions (e.g., in vivo). Therefore, hES-MC can function
      as microvascular MCs and may be a useful cell source for testing EC-MC
      interactions.

PMID- 22971007
TI  - Migration strategy affects avian influenza dynamics in mallards (Anas
      platyrhynchos).
AB  - Studies of pathogen transmission typically overlook that wildlife hosts can
      include both migrant and resident populations when attempting to model
      circulation. Through the application of stable isotopes in flight feathers, we
      estimated the migration strategy of mallards (Anas platyrhynchos) occurring on
      California wintering grounds. Our study demonstrates that mallards- a principal
      host of avian influenza virus (AIV) in nature, contribute differently to virus
      gene flow depending on migration strategy. No difference in AIV prevalence was
      detected between resident (9.6%), intermediate-distance (9.6%) and long-distance
      migrants (7.4%). Viral diversity among the three groups was also comparable,
      possibly owing to viral pool mixing when birds converge at wetlands during
      winter. However, migrants and residents contributed differently to the virus gene
      pool at wintering wetlands. Migrants introduced virus from northern breeding
      grounds (Alaska and the NW Pacific Rim) into the wintering population,
      facilitating gene flow at continental scales, but circulation of imported virus
      appeared to be limited. In contrast, resident mallards acted as AIV reservoirs
      facilitating year-round circulation of limited subtypes (i.e. H5N2) at lower
      latitudes. This study supports a model of virus exchange in temperate regions
      driven by the convergence of wild birds with separate geographic origins and
      exposure histories.

PMID- 22971008
TI  - Tear film break-up time in rabbits.
AB  - BACKGROUND: Rabbits have a longer inter-blink time (approximately 10 minutes)
      compared with humans (five to eight seconds), suggesting that rabbits have a much
      more stable tear film. Using fluorescein, the tear break-up time of rabbits has
      been reported to be similar to that of humans. This study set out to measure the
      tear break-up time in rabbits using non-invasive methods and to establish the
      pattern of tear break-up compared to humans. METHODS: The tear break-up time was
      measured and the pattern of tear break-up was observed in six New Zealand White
      rabbits on two separate occasions using both the Keeler Tearscope-plus(TM)  and a
      slitlamp biomicroscope. RESULTS: The mean rabbit tear break-up time was 29.8 +/-
      3.4 (SD) minutes. This contrasts with the reports of human tear break-up time of
      eight to 30 seconds. The tear breaking spread very slowly and was often
      restricted to the area of the initial break. CONCLUSION: Rabbit tears have a
      significantly higher tear break-up time than humans and this aligns with
      previously demonstrated differences in inter-blink time between rabbits and
      humans. Understanding the underlying mechanisms of tear stability may lead to
      novel ways of increasing human tear film stability.

PMID- 22971009
TI  - Robustness of Bayesian multilocus association models to cryptic relatedness.
AB  - Population-based association analyses are more powerful than within-family
      analyses in identifying genetic loci associated with a phenotype of interest.
      However, if the population or sample structure is omitted from the model,
      population stratification and cryptic relatedness may lead to false positive and
      negative signals caused by relatedness between individuals, rather than
      association due to close linkage of the marker and the trait loci. Therefore it
      is important to correct or account for these confounders in population-based
      association analyses. However, there is cumulative evidence that when fitting a
      multilocus association model, the genetic relationships between the individuals
      can be captured by the markers themselves, bringing about a possibility to use
      the models without an additional correction for the population or sample
      structure. In this work we have further investigated this possibility in the
      Bayesian multilocus association model context using the extended Bayesian LASSO
      and the indicator-based variable selection. In particular, we have studied
      whether these multilocus models benefit from an insertion of an additional
      polygenic term representing the genetic variation not captured by the markers and
      taking account of the residual dependencies between the individuals. We have
      found that although the models may benefit from the insertion of the polygenic
      component, omitting the component does not damage the model performance severely.

PMID- 22971010
TI  - Nitric oxide produced endogenously is responsible for hypoxia-induced HIF-1alpha
      stabilization in colon carcinoma cells.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a critical regulator of cellular
      responses to hypoxia. Under normoxic conditions, the cellular HIF-1alpha level is
      regulated by hydroxylation by prolyl hydroxylases (PHDs), ubiquitylation, and
      proteasomal degradation. During hypoxia, degradation decreases, and its
      intracellular level is increased. Exogenously administered nitric oxide (NO)
      donor drugs stabilize HIF-1alpha; thus, NO is suggested to mimic hypoxia.
      However, the role of low levels of endogenously produced NO generated during
      hypoxia in HIF-1alpha stabilization has not been defined. Here, we demonstrate
      that NO and reactive oxygen species (ROS) produced endogenously by human colon
      carcinoma HCT116 cells are responsible for HIF-1alpha accumulation in hypoxia.
      The antioxidant N-acetyl-L-cysteine (NAC) and NO synthase inhibitor N(G)
      monomethyl L-arginine (L-NMMA) effectively reduced HIF-1alpha stabilization and
      decreased HIF-1alpha hydroxylation. These effects suggested that endogenous NO
      and ROS impaired PHD activity, which was confirmed by reversal of L-NMMA- and NAC
      mediated effects in the presence of dimethyloxaloylglycine, a PHD inhibitor.
      Thiol reduction with dithiothreitol decreased HIF-1alpha stabilization in hypoxic
      cells, while dinitrochlorobenzene, which stabilizes S-nitrosothiols, favored its
      accumulation. This suggested that ROS- and NO-mediated HIF-1alpha stabilization
      involved S-nitrosation, which was confirmed by demonstrating increased S
      nitrosation of PHD2 during hypoxia. Our results support a regulatory mechanism of
      HIF-1alpha during hypoxia in which endogenously generated NO and ROS promote
      inhibition of PHD2 activity, probably by its S-nitrosation.

PMID- 22971011
TI  - Design, synthesis, and structure-activity relationships of novel pyrazolo[5,1
      b]thiazole derivatives as potent and orally active corticotropin-releasing factor
      1 receptor antagonists.
AB  - This paper describes the design, synthesis, and structure-activity relationships
      of a novel series of 7-dialkylamino-3-phenyl-6-methoxy pyrazolo[5,1-b]thiazole
      derivatives for use as selective antagonists of the corticotropin-releasing
      factor 1 (CRF(1)) receptor. The most promising compound, N-butyl-3-[4
      (ethoxymethyl)-2,6-dimethoxyphenyl]-6-methoxy-N-(tetrahydro-2H-pyran-4
      yl)pyrazolo[5,1-b][1,3]thiazole-7-amine (6t), showed high affinity (IC(50) = 70
      nM) and functional antagonism (IC(50) = 7.1 nM) for the human CRF(1) receptor as
      well as dose-dependent inhibition of the CRF-induced increase in the plasma
      adrenocorticotropic hormone (ACTH) concentration at a dose of 30 mg/kg (po).
      Further, in the light/dark test in mice, the compound 6t showed anxiolytic
      activity at a dose of 30 mg/kg (po).

PMID- 22971012
TI  - Kinetics and products of the reactions of OH radicals with cyclohexene, 1-methyl
      1-cyclohexene, cis-cyclooctene, and cis-cyclodecene.
AB  - Rate constants for the reactions of OH radicals with four C(6)-C(10) cycloalkenes
      have been measured at 297 +/- 2 K using a relative rate technique. The rate
      constants (in units of 10(-11) cm(3) molecule(-1) s(-1)) were cyclohexene, 6.35
      +/- 0.12; cis-cyclooctene, 5.16 +/- 0.15; cis-cyclodecene, 4.18 +/- 0.06; and 1
      methyl-1-cyclohexene, 9.81 +/- 0.18, where the indicated errors are two least
      squares standard deviations and do not include uncertainties in the rate constant
      for the reference compound 1,3,5-trimethylbenzene. In addition, a rate constant
      of (4.8 +/- 1.3) * 10(-11) cm(3) molecule(-1) s(-1) was derived for the reaction
      of OH radicals with 1,6-hexanedial, relative to our measured rate constant for OH
      + cyclohexene. Analyses of products of the OH + cyclohexene, 1-methyl-1
      cyclohexene, and cis-cyclooctene reactions by direct air sampling atmospheric
      pressure ionization mass spectrometry and/or by combined gas chromatography-mass
      spectrometry showed the presence of products attributed to cyclic 1,2
      hydroxynitrates and the dicarbonyls 1,6-hexanedial, 6-oxo-heptanal, and 1,8
      octanedial, respectively. These dicarbonyl products, which are those formed after
      decomposition of the intermediate cyclic 1,2-hydroxyalkoxy radicals, were
      quantified as their dioximes, with molar formation yields of 76 +/- 10%, 82 +/-
      12%, and 84 +/- 18% from the cyclohexene, 1-methyl-1-cyclohexene, and cis
      cyclooctene reactions, respectively. Combined with literature data concerning 1,2
      hydroxynitrate formation from OH + alkenes and the estimated fractions of the
      overall reactions proceeding by H-atom abstraction, 90 +/- 12%, 95 +/- 13% and
      108 +/- 20% of the products or reaction pathways from the OH radical-initiated
      reactions of cyclohexene, 1-methyl-1-cyclohexene, and cis-cyclooctene in the
      presence of NO are accounted for.

PMID- 22971013
TI  - Rationally designed aberrant kinase-targeted endogenous protein nanomedicine
      against oncogene mutated/amplified refractory chronic myeloid leukemia.
AB  - Deregulated protein kinases play a very critical role in tumorigenesis,
      metastasis, and drug resistance of cancer. Although molecularly targeted small
      molecule kinase inhibitors (SMI) are effective against many types of cancer,
      point mutations in the kinase domain impart drug resistance, a major challenge in
      the clinic. A classic example is chronic myeloid leukemia (CML) caused by BCR-ABL
      fusion protein, wherein a BCR-ABL kinase inhibitor, imatinib (IM), was highly
      successful in the early chronic phase of the disease, but failed in the advanced
      stages due to amplification of oncogene or point mutations in the drug-binding
      site of kinase domain. Here, by identifying critical molecular pathways
      responsible for the drug-resistance in refractory CML patient samples and a model
      cell line, we have rationally designed an endogenous protein nanomedicine
      targeted to both cell surface receptors and aberrantly activated secondary kinase
      in the oncogenic network. Molecular diagnosis revealed that, in addition to point
      mutations and amplification of oncogenic BCR-ABL kinase, relapsed/refractory
      patients exhibited significant activation of STAT5 signaling with correlative
      overexpression of transferrin receptors (TfR) on the cell membrane. Accordingly,
      we have developed a human serum albumin (HSA) based nanomedicine, loaded with
      STAT5 inhibitor (sorafenib), and surface conjugated the same with holo
      transferrin (Tf) ligands for TfR specific delivery. This dual-targeted
      "transferrin conjugated albumin bound sorafenib" nanomedicine (Tf-nAlb-Soraf),
      prepared using aqueous nanoprecipitation method, displayed uniform spherical
      morphology with average size of ~150 nm and drug encapsulation efficiency of
      ~74%. TfR specific uptake and enhanced antileukemic activity of the nanomedicine
      was found maximum in the most drug resistant patient sample having the highest
      level of STAT5 and TfR expression, thereby confirming the accuracy of our
      rational design and potential of dual-targeting approach. The nanomedicine
      induced downregulation of key survival pathways such as pSTAT5 and antiapoptotic
      protein MCL-1 was demonstrated using immunoblotting. This study reveals that, by
      implementing molecular diagnosis, personalized nanomedicines can be rationally
      designed and nanoengineered by imparting therapeutic functionality to endogenous
      proteins to overcome clinically important challenges like molecular drug
      resistance.

PMID- 22971014
TI  - Gaseous nitrogen and bacterial responses to raw and digested dairy manure
      applications in incubated soil.
AB  - A study was conducted under laboratory conditions to compare rates of nitrous
      oxide (N(2)O) and ammonia (NH(3)) emissions when soil was amended with
      anaerobically digested dairy manure slurry containing <30% food byproducts, raw
      dairy manure slurry, or urea. Slurries were applied via surface and subsurface
      methods. A second objective was to correlate genes regulating nitrification and
      denitrification with rates of N(2)O production, slurry treatment, and application
      method. Ammonia volatilization from incubated soil ranged from 140 g kg(-1) of
      total N applied in digested slurry to 230 g kg(-1) in urea. Subsurface
      application of raw dairy manure slurry decreased ammonia volatilization compared
      with surface application. Anaerobic digestion increased N(2)O production.
      Cumulative N(2)O loss averaged 27 g kg(-1) of total N applied for digested
      slurry, compared with 5 g kg(-1) for raw dairy slurry. Genes of interest included
      a 16S rRNA gene selective for beta-subgroup proteobacterial ammonia-oxidizers,
      amoA, narG, and nosZ quantified with quantitative polymerase chain reaction
      (qPCR) and real-time polymerase chain reaction (RT-PCR). Application of
      anaerobically digested slurry increased nitrifier and denitrifier gene copies
      that correlated with N(2)O production. Expression of all genes measured via mRNA
      levels was affected by N applications to soil. This study provides new
      information linking genetic markers in denitrifier and nitrifier populations to
      N(2)O production.

PMID- 22971015
TI  - The experience of mothers caring for a child with a brain tumour.
AB  - BACKGROUND: Brain tumours are the second most common form of childhood cancer,
      accounting for over 20% of all cases in European children. Understanding the
      impact of diagnosis and treatment of a brain tumour on the family is an essential
      pre-requisite to identifying ways to provide effective support. AIM: (1) To
      explore the impact of having a child with a brain tumour on the main caregiver in
      the family; (2) to describe mothers' experiences of coping with their child's
      illness, including personal barriers and strengths; and (3) to identify causes of
      stress and sources of support to inform improvements in care delivery. METHOD:
      Participants were drawn from a group of caregivers enrolled in a longitudinal
      study of outcome following diagnosis of a childhood brain tumour. Six caregivers
      took part, two from each of the high-, medium- and low-impact groups based on
      their Impact on Families Scale scores. Semi-structured interviews were used, with
      questions covering: (1) impact of the diagnosis on main caregiver and family; (2)
      personal barriers and strengths; and (3) causes of stress and sources of support.
      Interviews were transcribed verbatim and coded manually into five themes, which
      comprised 19 subthemes. FINDINGS: Coping methods and provision of help and
      support were major preoccupations for main caregivers from all impact groups.
      Caregivers in the high-impact group reported less conflict. High- and medium
      impact group caregivers had experienced less 'hindrance and heartache', than
      those with low impact scores, suggesting that the stress associated with
      diagnosis and treatment of the tumour may have increased cohesion and acceptance
      within these families. CONCLUSION: Families of children diagnosed with a brain
      tumour experience considerable negative impact and may perceive themselves as
      struggling to cope. Provision of help and support, within and outside the
      extended family, including from health, education and other services, is
      perceived as helpful.

PMID- 22971016
TI  - eHealth: individualisation of infliximab treatment and disease course via a self
      managed web-based solution in Crohn's disease.
AB  - BACKGROUND: Infliximab (IFX) maintenance therapy for Crohn's disease (CD) is
      administered every 8 weeks, but inter-patient variation in optimal treatment
      intervals may exist. AIM: To assess, in a prospective pilot study, the efficacy,
      safety and quality of life (QoL) of IFX maintenance treatment scheduled through
      web-based self-monitoring of disease activity. METHODS: Twenty-seven CD patients
      in IFX maintenance therapy were enrolled and received a standardised disease
      education and web-training. Using the http://www.cd.constant-care.dk concept,
      patients recorded their disease activity and faecal calprotectin weekly. From
      this, the inflammatory burden (IB) score was calculated, placing patients in the
      green, yellow or red zones of a 'traffic light' system. If placed in the yellow
      or red zones, the computer directed these patients to consult their physician for
      IFX infusion. RESULTS: Seventeen patients (63%) completed 52 weeks of follow-up,
      6 (22%) completed 26 weeks and 4 (15%) were excluded due to loss of response,
      patient decision or non-adherence. In total, 121 IFX infusions were given with a
      median interval of 9 (range: 4-18) weeks. Only 10% of infusions were given at 8
      week intervals, whereas 39% were administered with shorter and 50% with longer
      intervals respectively. The mean IB and the QoL remained stable during the web
      treatment. One mild infusion reaction and one case of folliculitis were observed,
      while three patients underwent surgery. CONCLUSIONS: The program
      http://www.cd.constant-care.dk appears to be a practical and safe concept for the
      individualised scheduling of maintenance treatment with IFX in patients with
      Crohn's disease. Larger studies are awaited to confirm this preliminary outcome.

PMID- 22971017
TI  - Acute acalculous cholecystitis after radical cystectomy: a report of two cases.

PMID- 22971020
TI  - Mucosal serpin A1 and A3 levels in HIV highly exposed sero-negative women are
      affected by the menstrual cycle and hormonal contraceptives but are independent
      of epidemiological confounders.
AB  - OBJECTIVE: Serpins (serine protease inhibitors) are associated with protection
      against HIV infection. Here, we characterized mucosal serpin expression in the
      genital tract of HIV highly exposed sero-negative (HESN) women meeting our
      epidemiological definition of HIV resistance in relation to epidemiological
      variables. METHODS: Cervicovaginal lavage (CVL) fluid and plasma were collected
      from 84 HIV-resistant, 54 HIV-uninfected, and 66 HIV-infected female commercial
      sex workers. Serpin A1 and A3 concentrations were measured by ELISA and compared
      with clinical information. RESULTS: Mucosal serpin A1 was elevated during
      proliferative phase over secretory phase (P = 0.017*), while A3 remained similar
      (P = 0.25). Plasma and mucosal serpin A1/A3 levels were not associated with each
      other and appeared compartment specific (r = 0.21, r = 0.056). Serpin A1/A3
      expression did not associate with age (r = 0.009, r = -0.06), duration of sex
      work (r = 0.13, r = -0.10), clients per day (r = -0.11, r = -0.02), concurrent
      STIs (P = 0.36, P = 0.15), but was lower in women using hormonal contraceptives
      (P = 0.034, P = 0.008). Mucosal serpin A1/A3 levels in HIV-infected individuals
      were not significantly different with disease status as determined by plasma
      CD4(+) T-cell counts (P = 0.94, P = 0.30). CONCLUSION: This study shows the
      relationship of serpins to the menstrual cycle and hormonal contraceptives, as
      well as their independence to epidemiological sexual confounders. This
      information provides a broader understanding of innate components of the mucosal
      immune system in women.

PMID- 22971018
TI  - Alcohol use predicts sexual risk behavior with HIV-negative or partners of
      unknown status among young HIV-positive men who have sex with men.
AB  - Although the relationship between substance use and heightened sexual risk
      behaviors have been documented in samples of young men who have sex with men
      (YMSM) and HIV-positive adult men who have sex with men (MSM), there is a dearth
      of research on the role of substance use in the sexual risk behaviors of HIV
      positive YMSM. We examined associations between alcohol and other drug use with
      sexual risk behaviors among a sample of HIV-positive YMSM (N=200). There were no
      significant predictors of either receptive or insertive unprotected anal
      intercourse (UAI) with HIV-positive partners among the substance use variables.
      Failure to use a condom after drinking alcohol (beta=2.00, p<0.01) was
      significantly associated with insertive UAI with HIV-negative partners or
      partners of unknown status. Failure to use a condom after drinking alcohol
      (beta=1.36, p<0.05) and age (beta=0.35, p<0.05) were significantly associated
      with receptive UAI with HIV-negative partners or partners of unknown status.
      Findings from this article underscore the role of alcohol in facilitating UAI
      among HIV-positive YMSM and their HIV-negative and status-unknown partners.

PMID- 22971021
TI  - Induced transition of CdSe nanoparticle superstructures by controlling the
      internal flow of colloidal solution.
AB  - The self-assembly behaviors of flow-enhanced CdSe nanoparticle (NP) colloidal
      systems were investigated, which were systemically prepared by adding ethylene
      glycol (EG) or acetic acid (AA) to NP suspensions with deionized water (DI water)
      base. The additive solvents, which had higher boiling points and lower surface
      tensions than those of the DI water, modified the internal flow of the NP
      colloidal system, consequently affecting the morphologies of the generated NP
      superstructures after the full evaporation of their droplets. In flow-enhanced
      systems, NPs were formed into highly elongated dendrites that stretched from the
      center region to the edges along the direction of convective flow inside the
      droplet, while NPs in random drift system were easily aggregated to form cluster
      shaped thick dendritic structures. When the volume fraction of EG was increased,
      the dominant superstructures were changed from dendrites to clusters, which can
      be mainly attributed to the changes in the dielectric properties of the NP
      droplets as evaporation proceeded because of the large discrepancy in the vapor
      pressures of EG and DI water. The balance between the interparticle potentials of
      electrostatic repulsion and van der Waals attraction was continuously altered,
      resulting in the formation of clusters with increasing EG ratio. Contrastively,
      the transition of superstructures could not be observed in the case of colloidal
      system prepared by mixing DI water and AA, which can be ascribed to the similar
      vapor pressures of the two solvents; the dielectric properties of the solution
      mixture was barely changed throughout the steady evaporation process, which
      resulted in the formation of uniformly distributed highly elongated dendrites.
      Polarization-dependent imaging experiments and photoluminescence measurements
      revealed that the stretched dendrites formed under the flow-enhanced conditions
      showed higher crystallinity than that of the clusters.

PMID- 22971019
TI  - Local recurrence of breast cancer after mastectomy and modern multidisciplinary
      treatment.
AB  - BACKGROUND: To study the incidence of local recurrence (LR) of early breast
      cancer in the ipsilateral thoracic wall after mastectomy and outcome of patients
      with LR. MATERIAL AND METHODS: A retrospective cohort study based on 2220
      consecutive breast cancer patients treated at the Helsinki University Central
      Hospital, Finland, in 2000 to 2003. A subset of 755 (34.0%) patients had
      mastectomy which was usually followed by postoperative radiotherapy (51.2%)
      and/or systemic adjuvant therapy (79.2%). RESULTS: During a median follow-up of
      89 months, 22 (2.9%) patients treated with mastectomy had LR. The median time to
      LR was 27 months. None of the 12 patient- or tumour-related standard risk factors
      studied were independently associated with LR-free survival in a multivariate
      model. Six (27.3%) of the 22 patients with LR had distant metastases diagnosed
      either prior to or simultaneously with LR. The subset of 16 patients who were
      diagnosed with LR without concomitant distant recurrence had five-year breast
      cancer-specific survival of 77.5% as calculated from the date of LR detection,
      and overall survival of 59.2%. CONCLUSIONS: LR after mastectomy has become a rare
      event. Most women with isolated LR survive for five years after LR.

PMID- 22971022
TI  - West Nile virus in north-eastern Italy, 2011: entomological and equine IgM-based
      surveillance to detect active virus circulation.
AB  - Since 2008, West Nile Virus (WNV) has expanded its range in several Italian
      regions, and its yearly recurrence suggests the virus may have become endemic in
      some areas. In 2011, a new plan based also on the detection of IgM antibodies was
      implemented in the north-eastern Italian regions of Veneto and Friuli Venezia
      Giulia, aiming to early detect WNV infections in areas where the virus had
      already circulated during the previous summers, and in adjacent zones. From July
      to November 2011, 1880 sera from 521 equine premises were screened by a
      commercial IgM capture ELISA. Mosquitoes were captured by CDC-CO2 traps at 61
      locations in the two regions. Collected mosquitoes were identified, pooled by
      species/date/location and examined by real-time RT-PCR and sequencing. Passive
      surveillance was carried out on clinically affected horses and non-migratory wild
      birds found dead. IgM sero-positive equines were detected in 19 holdings, five in
      the area with WNV circulation (AWC) and 14 in the surveillance area (SA); 10 more
      horse premises tested positive to further serological controls within 4 km of the
      positive holdings. A total of 85,398 mosquitoes of 15 species were collected and
      2732 pools examined. Five Culex pipiens pools tested positive for the presence of
      WNV. Passive surveillance on non-migratory wild birds allowed detection of the
      virus only in one found dead collared dove (Streptopelia decaocto), of 82 birds
      sampled. The WNV belonged to the lineage 2, which had been isolated for the first
      time in Italy earlier in 2011. By the first week of October, nine human cases had
      been confirmed in the same area. The implementation of a protocol combining IgM
      screening of horses with surveillance on mosquito vectors proved to be valuable
      for early detecting WNV circulation.

PMID- 22971024
TI  - Will electronic health records improve healthcare quality? Challenges and future
      prospects.

PMID- 22971023
TI  - Periodontal healing complications following extrusive and lateral luxation in the
      permanent dentition: a longitudinal cohort study.
AB  - PURPOSE: To analyze the risk of tooth loss and complications in periodontal
      ligament (PDL) healing following extrusive and lateral luxation in the permanent
      dentition. MATERIALS AND METHODS: Eighty-two permanent teeth (78 patients) with
      extrusive luxation and 179 teeth (149 patients) with lateral luxation were
      included in the study. All teeth were examined according to a standardized
      protocol including clinical, photographic, and radiographic registration. Follow
      up controls were performed at regular intervals (3, 6 weeks, 6 months, 1, 5, and
      10 years). STATISTICS: The risk of repair-related resorption (surface
      resorption), infection-related resorption (inflammatory resorption), ankylosis
      related resorption (replacement resorption), marginal bone loss, and tooth loss
      was analyzed with the Kaplan-Meier method. Differences among subgroups were
      analyzed with log-rank test and Cox regression. RESULTS: The risk of periodontal
      healing complications was estimated after 3 years. Extrusive luxation: For
      immature root development, infection-related resorption was 2.4% (95% confidence
      interval (CI): 0-6.9%). For mature root development, repair-related resorption
      was 15.6% (95% CI: 4.4-26.7%), infection-related resorption was 5.1% (95% CI: 0
      11.7%), and marginal bone loss was 17.5% (95% CI: 6.2-28.8%). No teeth showed
      ankylosis-related resorption, and no teeth were lost in the observation period.
      Lateral luxation: For immature root development, repair-related resorption was
      2.1% (95% CI: 0-6.1%), infection-related resorption was 2.1% (95% CI: 0-6.1%).
      For mature root development, repair-related resorption was 29.5% (95% CI: 20.5
      38.5%), infection-related resorption was 2.6% (95% CI: 0-6.4%), ankylosis-related
      resorption was 0.8% (95% CI: 0-2.3%), marginal bone loss was 6.9% (95% CI: 2.2
      11.6%). CONCLUSION: The risk of severe periodontal healing complications in teeth
      with extrusive and lateral luxation injuries is generally low. Marginal bone loss
      and repair-related resorption occurred significantly more often in teeth with
      mature rather than immature root development. Marginal bone loss was associated
      with injuries involving multiple teeth.

PMID- 22971025
TI  - Public reporting of transplant center outcomes: an incentive for improved patient
      care?

PMID- 22971027
TI  - Update on tolvaptan for the treatment of hyponatremia.
AB  - Tolvaptan is a member of a new class of drugs, called the vaptans, that
      antagonize receptors of the neurohormone arginine vasopressin. From a clinical
      perspective, tolvaptan has been shown to be efficacious in the treatment of
      hyponatremia, whether it is idiopathic or disease related, and it may have a more
      favorable benefit/risk profile than other treatment modalities. From an economic
      perspective, tolvaptan is an expensive drug for treating hyponatremia, but recent
      economic cost-offset models provide evidence that tolvaptan can be cost
      effective. The cost-effectiveness of tolvaptan is driven by reduced healthcare
      resource usage and hospitalization costs. More comparative research of tolvaptan
      versus other pharmacotherapies and analyses of patients treated with tolvaptan in
      the real world are needed to better determine the benefits of tolvaptan usage to
      patient outcome, and more accurately assess its value in the treatment of
      hyponatremia, an independent predictor of morbidity, mortality and cost.

PMID- 22971028
TI  - Clinical and economic review of erlotinib in non-small-cell lung cancer.
AB  - Lung cancer has the highest incidence and mortality among cancers of both men and
      women. Treatment strategies for non-small-cell lung cancer, the most common form
      of lung cancer, continue to evolve, most recently with the positive trial results
      for EGF receptor (EGFR) tyrosine kinase inhibitors in the first-line setting in
      molecularly targeted populations. Despite these promising findings, EGFR tyrosine
      kinase inhibitors remain costly, and it is therefore important to assess the
      value of erlotinib therapy across the full spectrum of use. This is an up-to-date
      review of the clinical and economic impact of erlotinib for advanced non-small
      cell lung cancer. Overall, the studies found that erlotinib, compared with
      available agents, provides slightly improved outcomes with variability in the
      incremental costs depending on the health system and patient characteristics.
      Additional studies are warranted exploring the cost-effectiveness of erlotinib as
      a first-line agent as well as the clinical and economic impact of EGFR mutation
      testing strategies versus usual care.

PMID- 22971029
TI  - Improving the managed entry of new medicines: sharing experiences across Europe.
AB  - The 3-day course on the managed entry of new medicines was run by the Piperska
      group, which is a pan-European group striving to enhance the health of the public
      as a whole and the individual patient through exchanging ideas and research
      around the rational use of drugs. Participants included health authority and
      health insurance personnel, academics and those from commercial organizations.
      The principal aim of the conference was to bring together people to discuss ways
      to improve the managed entry of new drugs.

PMID- 22971030
TI  - Promoting pan-European cancer research for the benefit of all cancer patients.
AB  - The European Organisation for Research and Treatment of Cancer (EORTC) 50th
      Anniversary Conference was held on the 15-16 March in Brussels, Belgium. More
      than 1100 participants (including EORTC members and staff, national research
      organizations, health authorities, patient advocacy groups, European Commission,
      cancer leagues and the pharmaceutical industry) registered for this conference
      that offered a unique opportunity to gather all the partners involved in the
      EORTC mission. The EORTC has been a pioneer in promoting multidisciplinary cancer
      research in a pan-European setting with a mission to improve the standard of
      cancer treatment for patients with cancer. This conference highlighted the
      tremendous progress that has been made over the past 50 years and pointed to the
      challenges that will be faced in the future.

PMID- 22971031
TI  - Intensity-modulated radiation therapy for prostate cancer is cost effective and
      improves therapeutic ratio.
AB  - Radiation therapy is one of the standard treatment options for many prostate
      cancer patients. Intensity-modulated radiation therapy (IMRT) allows for more
      conformal dose distributions that can reduce normal tissue toxicity compared with
      older external beam techniques. There has been a rapid adoption of IMRT between
      2001 and 2007 for prostate cancer patients regardless of the patients' race,
      socioeconomic status or disease risk classification. IMRT is more expensive than
      older radiation techniques and has an impact on healthcare spending for prostate
      cancer.

PMID- 22971032
TI  - Impact of lifestyle factors on prognosis among breast cancer survivors in the
      USA.
AB  - Advances in diagnostic screening and adjuvant therapy have dramatically increased
      the number of breast cancer survivors in the USA, who may face changes in
      physical and mental health, social support, quality of life and economics. Women
      living with breast cancer are increasingly interested in lifestyle modification
      to decrease the risk of recurrence and mortality while increasing physical and
      emotional wellbeing. Although organizations such as the American Cancer Society
      support a healthy diet, frequent physical activity and stress reduction for
      decreasing breast cancer risk, studies examining the effects of lifestyle on
      clinical outcomes including survival and prognosis have been inconclusive. With
      the number of breast cancer survivors predicted to increase to 3.4 million by
      2015, it is important to develop effective treatment paradigms that overcome
      barriers to behavioral modification to improve clinical outcomes and survivorship
      in breast cancer patients.

PMID- 22971033
TI  - Impact of restricting access to high-cost medications for hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, and
      its incidence is increasing in the West, including the UK, with the increasing
      burden of chronic liver disease. Until recently, systemic treatment options for
      advanced disease were limited. However, randomized clinical trials have
      demonstrated that the multikinase inhibitor sorafenib prolongs survival in
      appropriately selected patients, and this drug has become the standard of care
      for patients with advanced HCC. However, a single-technology appraisal by the
      NICE recommended that the UK National Health Service should not fund sorafenib on
      the grounds of cost-effectiveness. A number of other novel agents and
      combinations are currently in clinical trials, the results of which may further
      expand the treatment options and indications for systemic therapy in HCC. This
      review discusses the impact of restricting access to high-cost medications for
      patients with HCC in the UK, and describes potential strategies and future
      directions that may improve the cost-effectiveness of such drugs. It also
      describes the potential impact, pending national guidance, of variations in local
      funding decision-making on patient outcomes.

PMID- 22971034
TI  - Meaningful change in oncology quality-of-life instruments: a systematic
      literature review.
AB  - Quality of life (QoL) is increasingly being recognized as an important end point
      in oncology clinical trials. The purpose of this study was to review the
      literature on what constitutes a meaningful change in oncology QoL instruments. A
      literature search was conducted in Medline, Embase, Cochrane Central Register of
      Controlled Trials and Cochrane Database of Systematic Reviews. Articles
      determining clinically meaningful change were selected. Twenty six publications
      were identified. Common anchors included performance status, global rating of
      change and overall QoL. The distribution approach utilized standard deviations
      and standard error of measurement. Limitations included optimism bias and a
      change in patients' internal frame of reference. Currently, there is an
      inconsistency between meaningful change studies. Analyses should be conducted in
      population-specific samples, as meaningful change varies depending on patient
      characteristics. Consistently, meaningful change for improvement has been smaller
      than that for deterioration, suggesting that patients are more responsive to
      improvement.

PMID- 22971036
TI  - Economic outcomes for celecoxib: a systematic review of pharmacoeconomic studies.
AB  - Osteoarthritis and rheumatoid arthritis are conditions that are associated with
      significant clinical burden, and impact on patients' functional status and
      quality of life. Medical costs related to treating these common and disabling
      conditions place an economic strain on healthcare systems. This systematic review
      was conducted to investigate the impact of celecoxib on healthcare costs for
      patients with rheumatoid arthritis and osteoarthritis. In total, 24 studies
      examined economic outcomes associated with celecoxib in patients with these
      conditions. Six of these studies evaluated economic outcomes in developing
      regions, including Mexico, Asia and Turkey. Across all geographies, most studies
      were cost-effectiveness analyses comparing celecoxib with nonselective NSAIDs
      alone or in combination with gastroprotective agents. Overall, based on local
      standards, economic models indicated favorable cost-effectiveness profiles for
      celecoxib compared with nonselective NSAIDs and other active-treatment options.
      Cost analyses indicated that the use of celecoxib resulted in lower direct
      medical costs.

PMID- 22971035
TI  - Autism spectrum disorders: a review of measures for clinical, health services and
      cost-effectiveness applications.
AB  - Autism spectrum disorders (ASDs) are characterized by impairments in social
      interaction, communication and behavioral functioning that can affect the health
      related quality-of-life outcomes of the affected child and the family. ASDs have
      increased in prevalence, leading to a demand for improved understanding of the
      comparative effectiveness of different pharmacologic, behavioral, medical and
      alternative treatments for children as well as systems for providing services.
      This review describes outcome instruments that can be used for clinical, health
      services and cost-effectiveness applications. There is a pressing need to
      identify the most appropriate instruments for measuring health-related quality-of
      life outcomes in this population. Studies evaluating the cost-effectiveness of
      interventions or treatments for children with ASDs using the cost per quality
      adjusted life year metric are lacking. Researchers have the potential to
      contribute greatly to the field of autism by quantifying outcomes that can inform
      optimal treatment strategies.

PMID- 22971038
TI  - Meta-analysis of simultaneous versus staged resection for synchronous colorectal
      liver metastases.
AB  - AIM:   There is no clear consensus on the optimal timing of surgical resection
      for synchronous colorectal liver metastases (SCLM). This study is a meta-analysis
      of the available evidence. METHODS:   Systematic review and meta-analysis of
      trials comparing outcomes following simultaneous resection with staged resection
      for SCLM published from 1990 to 2010 in PubMed, Embase, Ovid and Medline. Pooled
      odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals
      (95% CI) were calculated using either the fixed effects or random effects model.
      RESULTS:   Nineteen non-randomized controlled trials (NRCT) studies were included
      in this analysis. These studies included a total of 2724 patients: 1116 underwent
      simultaneous resection and 1608 underwent staged resection. Meta-analysis showed
      that shorter hospital stay (P < 0.001) and lower total complication rate (P <
      0.001) were observed in patients undergoing simultaneous resection group. The
      overall survival rate in the simultaneous resection group did not statistically
      differ with that in the staged resection group at 1 year (P = 0.13), 3 years (P =
      0.26), 5 years (P = 0.38), as well as the 1, 3 and 5 years disease-free survival
      rates (respectively, P = 0.55; P = 0.16; P = 0.12). No significant difference was
      noted between the two groups in terms of mortality (P = 0.16), intraoperative
      blood loss (P = 0.06) and recurrence (P = 0.47). CONCLUSION:   Simultaneous
      resection is safe and efficient in the treatment of patients with SCLM while
      avoiding a second laparotomy. In selected patients, simultaneous resection might
      be considered as the preferred approach. However, the findings have to be
      carefully interpreted due to the lower level of evidence and the existence of
      heterogeneity.

PMID- 22971039
TI  - Reduction of mycotoxins in white pepper.
AB  - A simple method for the reduction of aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1),
      G2 (AFG2) and ochratoxin A (OTA) in white pepper was studied. Response surface
      methodology (RSM) was applied to determine the effect of four variables, which
      included time (20-60 min), temperature (30-70 degrees C), calcium hydroxide
      (Ca(OH)2) (0-1%) and hydrogen peroxide (H2O2) (1-3%) during the washing step of
      white pepper. The efficacy of the method was evaluated by the determination of
      mycotoxins by HPLC with fluorescence detection (FD). Statistical analysis showed
      that the experimental data could be adequately fitted into a second-order
      polynomial model, with a multiple regression coefficient (R2) in the range of
      0.805-0.907 for AFG2 and AFG1, respectively. The optimal condition was 57.8 min,
      62.0 degrees C, of 0.6% (w/v) and 2.8% (v/v) for time, temperature, Ca(OH)2 and
      H2O2 respectively. By applying the optimum condition, the mycotoxins reduction
      was found to be in the range of 68.5-100% for AFB2 and AFG1 respectively.

PMID- 22971040
TI  - Prognostic factors determining survival in patients with node positive
      differentiated thyroid cancer: a retrospective cross-sectional study.
AB  - OBJECTIVE: The prognostic factors for the disease-free status and overall
      survival among patients who had differentiated thyroid cancer with cervical lymph
      node metastasis were evaluated to develop a better understanding of the possible
      effects of lymph node metastasis on the disease process. DESIGN: The data from
      101 patients who underwent modified radical neck dissection to determine the
      presence of cervical node positive differentiated thyroid cancer was evaluated
      and disease-free survival and overall survival rates were calculated. Prognostic
      factors predicting these survival rates were evaluated. SETTING: This research
      took place between July of 1994 and December of 2006 in the Department of General
      Surgery at Ankara Oncology Training and Research Hospital. PARTICIPANTS: One
      hundred and one patients underwent a modified radical neck dissection after the
      cervical nodes were assessed as positive for the presence of cancer. MAIN OUTCOME
      MEASURES: Ten-year disease-free survival and overall survival rates were
      measured. RESULTS: We calculated the 10-year disease-free survival rate at 67.3%
      and the overall survival rate at 86.1%. Age, thyroidal extracapsular invasion,
      vascular invasion, metastasis, age, completeness of resection, size score and TNM
      staging were found to be relevant to disease-free survival and overall survival
      in both the univariate and the multivariate analyses. While the age, metastasis,
      extent of disease score was relevant to disease-free survival and overall
      survival in the univariate analysis, this association is not found in the
      multivariate analysis. The histological type of the tumour was not predictive of
      disease-free survival, but the follicular type was closely related to the
      prognosis for overall survival. CONCLUSION: Cervical node metastasis in thyroid
      carcinoma slightly reduces overall survival. Prognostic factors can help identify
      high-risk patients and point towards an adequate therapeutic approach.

PMID- 22971041
TI  - The German adaptation of the Cambridge Pulmonary Hypertension Outcome Review
      (CAMPHOR).
AB  - BACKGROUND: Individuals with precapillary pulmonary hypertension (PH) experience
      severely impaired quality of life. A disease-specific outcome measure for PH, the
      Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was developed and
      validated in the UK and subsequently adapted for use in additional countries. The
      aim of this study was to translate and assess the reliability and validity of the
      CAMPHOR for German-speaking populations. METHODS: Three main adaptation stages
      involved; translation (employing bilingual and lay panels), cognitive debriefing
      interviews with patients and validation (assessment of the adaptation's
      psychometric properties). The psychometric evaluation included 107 patients with
      precapillary PH (60 females; age mean (standard deviation) 60 (15) years) from 3
      centres in Austria, Germany and Switzerland. RESULTS: No major problems were
      found with the translation process with most items easily rendered into
      acceptable German. Participants in the cognitive debriefing interviews found the
      questionnaires relevant, comprehensive and easy to complete. Psychometric
      analyses showed that the adaptation was successful. The three CAMPHOR scales
      (symptoms, activity limitations and quality of life) had excellent test-retest
      reliability correlations (Symptoms = 0.91; Activity limitations = 0.91; QoL =
      0.90) and internal consistency (Symptoms = 0.94; Activity limitations = 0.93; QoL
      = 0.94). Predicted correlations with the Nottingham Health Profile provided
      evidence of the construct validity of the CAMPHOR scales. The CAMPHOR adaptation
      also showed known group validity in its ability to distinguish between
      participants based on perceived general health, perceived disease severity,
      oxygen use and NYHA classification. CONCLUSIONS: The CAMPHOR has been shown to be
      valid and reliable in the German population and is recommend for use in clinical
      practice.

PMID- 22971042
TI  - Internet-based psychoeducation for bipolar disorder: a qualitative analysis of
      feasibility, acceptability and impact.
AB  - BACKGROUND: In a recent exploratory randomised trial we found that a novel,
      internet-based psychoeducation programme for bipolar disorder (Beating Bipolar)
      was relatively easy to deliver and had a modest effect on psychological quality
      of life. We sought to explore the experiences of participants with respect to
      feasibility, acceptability and impact of Beating Bipolar. METHODS: Participants
      were invited to take part in a semi-structured interview. Thematic analysis
      techniques were employed; to explore and describe participants' experiences, the
      data were analysed for emerging themes which were identified and coded. RESULTS:
      The programme was feasible to deliver and acceptable to participants where they
      felt comfortable using a computer. It was found to impact upon insight into
      illness, health behaviour, personal routines and positive attitudes towards
      medication. Many participants regarded the programme as likely to be most
      beneficial for those recently diagnosed. CONCLUSIONS: An online psychoeducation
      package for bipolar disorder, such as Beating Bipolar, is feasible and acceptable
      to patients, has a positive impact on self-management behaviours and may be
      particularly suited to early intervention. Alternative (non-internet) formats
      should also be made available to patients.

PMID- 22971043
TI  - Armanni-Ebstein lesions: a need for clarification.
AB  - Armanni-Ebstein lesions were first described by Luciano Armanni, a pathologist at
      the University of Naples, during autopsy studies undertaken in 1872, as a unique
      vacuolar nephropathy associated with poorly controlled diabetes that involves
      selective renal epithelial cell glycogen accumulation. However, within the last
      two decades, a broader range of vacuolar changes, including lipid deposition,
      have also been termed Armanni-Ebstein (AE) lesions, creating some confusion on
      possible etiology. We would suggest that the term AE phenomenon would be best
      reserved for the original clear cell change associated with glycogen deposition,
      and that this should be clearly distinguished from subnuclear lipid vacuolization
      ("basal vacuolization"). Although there is obvious inter-relation between these
      two types of vacuoles, they appear morphologically and biochemically distinct
      from each other. More precise classification may assist in clarifying the causal
      processes and possible diagnostic significance of different types of renal
      epithelial vacuolization at autopsy.

PMID- 22971044
TI  - Triggered "on/off" micropumps and colloidal photodiode.
AB  - We discuss a set of smart micropumps that sense their surrounding environment and
      respond accordingly. First we show that crystallites of a photoacid generator
      function as micropumps in the presence of UV light via diffusiophoresis and can
      be turned "on/off" in a controlled manner. The pump can be restarted multiple
      times simply by re-illumination. The electroosmotic component was distinguished
      from the diffusiophoretic component and compared. We also demonstrate patterning.
      Second, we show that a polymeric imine can also work as a micropump in acidic
      environment wherein the velocity can be controlled by controlling the pH and, in
      turn, the ion gradient; the highest velocities are achieved at the lowest pH.
      Finally, we combined the photoacid and polyimine pumps to create a colloidal
      photodiode, where we attain both spatial and temporal control over colloidal
      transport and obtain amplification along with rectification.

PMID- 22971046
TI  - Effect of macroalgal expansion and marine protected areas on coral recovery
      following a climatic disturbance.
AB  - Disturbance plays an important role in structuring marine ecosystems, and there
      is a need to understand how conservation practices, such as the designation of
      Marine Protected Areas (MPAs), facilitate postdisturbance recovery. We evaluated
      the association of MPAs, herbivorous fish biomass, substrate type,
      postdisturbance coral cover, and change in macroalgal cover with coral recovery
      on the fringing reefs of the inner Seychelle islands, where coral mortality after
      a 1998 bleaching event was extensive. We visually estimated benthic cover and
      fish biomass at 9 sites in MPAs where fishing is banned and at 12 sites where
      fishing is permitted in 1994, 2005, 2008, and 2011. We used analysis of variance
      to examine spatial and temporal variations in coral cover and generalized
      additive models to identify relations between coral recovery and the
      aforementioned factors that may promote recovery. Coral recovery occurred on all
      substrate types, but it was highly variable among sites and times. Between 2005
      and 2011 the increase in coral cover averaged 1%/year across 21 sites, and the
      maximum increase was 4%/year. However, mean coral cover across the study area
      (14%) remained at half of 1994 levels (28%). Sites within MPAs had faster rates
      of coral recovery than sites in fished areas only where cover of macroalgae was
      low and had not increased over time. In MPAs where macroalgae cover expanded
      since 1998 there was no recovery. Where coral was recovering on granite reefs
      there was a shift in relative prevalence of colony life-form from branching to
      encrusting species. This simplification of reef structure may affect associated
      reef fauna even if predisturbance levels of coral cover are attained.

PMID- 22971045
TI  - Patient and spouse illness beliefs and quality of life in prostate cancer
      patients.
AB  - OBJECTIVE: Among married prostate cancer (PC) patients, the spouse is often the
      primary provider of emotional support and personal care. However, few studies
      have investigated spouses' illness beliefs (i.e. about disease duration and
      treatment control) and their impact on patients' quality of life (QOL). Spouses'
      beliefs about disease duration (timeline) were hypothesised to mediate
      relationships between spouses' treatment control beliefs and patients' QOL six
      months later. METHODS: Fifty-three patients who underwent localised treatment for
      PC, and their spouses, completed an illness beliefs measure (the revised Illness
      Perception Questionnaire). Patients completed a QOL measure (the Functional
      Assessment of Cancer Therapy - General) six months later. RESULTS: Spouse
      timeline beliefs mediated the association between spouse treatment control
      beliefs and patient QOL six months later (total indirect effect = -0.71, 95% CI
      0.02-2.03). That is, spouse beliefs that the treatment would control their loved
      one's illness led to beliefs that the disease would be of shorter duration, which
      in turn led to improved patient QOL six months later. This relationship did not
      occur with patients' beliefs. CONCLUSION: Results highlight the important
      influence of spouse illness beliefs over time on patient QOL with implications
      for clinical care and dyadic research.

PMID- 22971047
TI  - Spatial analysis of ectomycorrhizal fungi reveals that root tip communities are
      structured by competitive interactions.
AB  - Microbial ecology has made large advances over the last decade, mostly because of
      improvements in molecular analysis techniques that have enabled the detection and
      identification of progressively larger numbers of microbial species. However,
      determining the ecological patterns and processes taking place in communities of
      microbes remains a significant challenge. Are communities randomly assembled
      through dispersal and priority effects, or do species interact with each other
      leading to positive and negative associations? For mycorrhizal fungi, evidence is
      accumulating that stochastic and competitive interactions between species may
      both have a role in shaping community structure. Could the methodological
      approach, which is often incidence based, impact the outcomes detected? Here, we
      applied an incidence-based Terminal Restriction Fragment Length Polymorphism (T
      RFLP) database approach to examine species diversity and ecological interactions
      within a community of ectomycorrhizal (ECM) fungi. Co-occurrence analysis
      revealed that the ECM community colonizing root tips was strongly structured by
      competitive interactions, or ecological processes generating a similar spatial
      pattern, rather than neutral processes. Analysis of beta-diversity indicated that
      community structure was significantly more similar (spatially autocorrelated) at
      distances equal to or <3.41 m. The eight most frequently encountered species in
      the root tip community of ECM fungi displayed significant competitive
      interactions with at least one other species, showing that the incidence-based
      approach was capable of detecting this sort of ecological information.

PMID- 22971048
TI  - Use of polyacrylamide gel moving boundary electrophoresis to enable low-power
      protein analysis in a compact microdevice.
AB  - In designing a protein electrophoresis platform composed of a single-inlet,
      single-outlet microchannel powered solely by voltage control (no pumps, values,
      injectors), we adapted the original protein electrophoresis format-moving
      boundary electrophoresis (MBE)-to a high-performance, compact microfluidic
      format. Key to the microfluidic adaptation is minimization of injection
      dispersion during sample injection. To reduce injection dispersion, we utilize a
      photopatterned free-solution-polyacrylamide gel (PAG) stacking interface at the
      head of the MBE microchannel. The nanoporous PAG molecular sieve physically
      induces a mobility shift that acts to enrich and sharpen protein fronts as
      proteins enter the microchannel. Various PAG configurations are characterized,
      with injection dispersion reduced by up to 85%. When employed for analysis of a
      model protein sample, microfluidic PAG MBE baseline-resolved species in 5 s and
      in a separation distance of less than 1 mm. PAG MBE thus demonstrates
      electrophoretic assays with minimal interfacing and sample handling, while
      maintaining separation performance. Owing to the short separation lengths needed
      in PAG MBE, we reduced the separation channel length to demonstrate an
      electrophoretic immunoassay powered with an off-the-shelf 9 V battery. The
      electrophoretic immunoassay consumed less than 3 MUW of power and was completed
      in 30 s. To our knowledge, this is the lowest voltage and lowest power
      electrophoretic protein separation reported. Looking forward, we see the low
      power PAG MBE as a basis for highly multiplexed protein separations (mobility
      shift screening assays) as well as for portable low-power diagnostic assays.

PMID- 22971051
TI  - Trifunctional metal ion-catalyzed solvolysis: Cu(II)-promoted methanolysis of N,N
      bis(2-picolyl) benzamides involves unusual Lewis acid activation of substrate,
      delivery of coordinated nucleophile, powerful assistance of the leaving group
      departure.
AB  - The methanolyses of Cu(II) complexes of a series of N,N-bis(2-picolyl) benzamides
      (4a-g) bearing substituents X on the aromatic ring were studied under (s)(s)pH
      controlled conditions at 25  degrees C. The active form of the complexes at
      neutral (s)(s)pH has a stoichiometry of 4:Cu(II):((-)OCH(3))(HOCH(3)) and
      decomposes unimolecularly with a rate constant k(x). A Hammett plot of log(k(x))
      vs sigma(x) values has a rho(x) of 0.80 +/- 0.05. Solvent deuterium kinetic
      isotope effects of 1.12 and 1.20 were determined for decomposition of the 4-nitro
      and 4-methoxy derivatives, 4b:Cu(II):((-)OCH(3))(HOCH(3)) and 4g:Cu(II):((
      )OCH(3))(HOCH(3)), in the plateau region of the (s)(s)pH/log(k(x)) profiles in
      both CH(3)OH and CH(3)OD. Activation parameters for decomposition of these
      complexes are DeltaH(++) = 19.1 and 21.3 kcal mol(-1) respectively and DeltaS(++)
      = -5.1 and -2 cal K(-1) mol(-1). Density functional theory (DFT) calculations for
      the reactions of the Cu(II):((-)OCH(3))(HOCH(3)) complexes of 4a,b and g (4a, X =
      3,5-dinitro) were conducted to probe the relative transition state energies and
      geometries of the different states. The experimental and computational data
      support a mechanism where the metal ion is coordinated to the N,N-bis(2-picolyl)
      amide unit and positioned so that it permits delivery of a coordinated Cu(II):((
      )OCH(3)) nucleophile to the C?O in the rate-limiting transition state (TS) of the
      reaction. This proceeds to a tetrahedral intermediate INT, occupying a shallow
      minimum on the free energy surface with the Cu(II) coordinated to both the
      methoxide and the amidic N. Breakdown of INT is a virtually barrierless process,
      involving a Cu(II)-assisted departure of the bis(2-picolyl)amide anion. The
      analysis of the data points to a trifunctional role for the metal ion in the
      solvolysis mechanism where it activates intramolecular nucleophilic attack on the
      C?O group by coordination to an amidic N in the first step of the reaction and
      subsequently assists leaving group departure in the second step. The catalysis is
      very large; compared with the second order rate constant for methoxide attack on
      4b, the computed reaction of CH3O(-) and 4b:Cu(II):(HOCH(3))(2) is accelerated by
      roughly 2.0 * 10(16) times.

PMID- 22971050
TI  - Risk factors and outcome of HIV-associated idiopathic noncirrhotic portal
      hypertension.
AB  - BACKGROUND: Idiopathic noncirrhotic portal hypertension (INCPH) has been reported
      increasingly in patients with HIV infection. AIM: To evaluate the number of
      nationwide diagnosed HIV-associated INCPH cases and to assess its clinical
      features, risk factors and outcome. METHODS: All HIV centres in the Netherlands
      were contacted and requested to notify INCPH cases diagnosed in their population.
      A case-control study was performed to identify the risk factors of INCPH. The
      cases were group-matched for duration of follow-up after HIV diagnosis to
      controls. Controls were selected from a database of HIV patients with negative
      screening for signs of portal hypertension on abdominal ultrasound. Univariate
      and multivariate conditional logistic regression analyses were performed.
      RESULTS: On 1st of July 2011, 18.085 individuals were infected with HIV in the
      Netherlands. Within this population, sixteen patients with clinically overt INCPH
      were identified. At the time of INCPH diagnosis, cases had a lower platelet count
      and a higher ALT level. In univariate and multivariate analyses, didanosine [OR:
      1.9 (1.3-2.8)], concomitant didanosine and stavudine treatment [OR: 6.3 (2.1
      19.1)] and concomitant didanosine and tenofovir treatment [OR: 5.1 (1.2-22.6)]
      were independently associated INCPH. During follow-up, 4 patients died
      [malignancy (n = 3), liver failure (n = 1)]. A significant decline in platelets
      was observed after didanosine discontinuation (P = 0.003). CONCLUSIONS: HIV
      associated clinically relevant idiopathic noncirrhotic portal hypertension
      appears to be a rarely diagnosed disease. Long-term exposure to didanosine and
      short-term combination of didanosine and stavudine or tenofovir exposure are
      associated with idiopathic noncirrhotic portal hypertension. Mortality in HIV
      associated idiopathic noncirrhotic portal hypertension is mainly related to HIV
      associated disorders. Portal hypertension continues despite didanosine
      discontinuation

PMID- 22971049
TI  - Proteomic analysis of Chinese hamster ovary cells.
AB  - To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells,
      proteomic analysis was performed on CHO cells including the cellular proteome,
      secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple
      fractions obtained from gel electrophoresis, multidimensional liquid
      chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120
      different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548
      unique peptide sequences were identified with at most 0.02 false discovery rate
      (FDR). A total of 6164 grouped proteins were identified from both glycoproteome
      and proteome analysis, representing an 8-fold increase in the number of proteins
      currently identified in the CHO proteome. Furthermore, this is the first
      proteomic study done using the CHO genome exclusively, which provides for more
      accurate identification of proteins. From this analysis, the CHO codon frequency
      was determined and found to be distinct from humans, which will facilitate
      expression of human proteins in CHO cells. Analysis of the combined proteomic and
      mRNA data sets indicated the enrichment of a number of pathways including protein
      processing and apoptosis but depletion of proteins involved in steroid hormone
      and glycosphingolipid metabolism. Five-hundred four of the detected proteins
      included N-acetylation modifications, and 1292 different proteins were observed
      to be N-glycosylated. This first large-scale proteomic analysis will enhance the
      knowledge base about CHO capabilities for recombinant expression and provide
      information useful in cell engineering efforts aimed at modifying CHO cellular
      functions.

PMID- 22971052
TI  - Short- and long-term effects of exposure to natural and synthetic glucocorticoids
      during development.
AB  - 1.Glucocorticoids (GCs) are necessary for fetal development, but clinical and
      experimental studies suggest that excess exposure may be detrimental to health in
      both the short and longer term. 2.Exposure of the fetus to synthetic GCs can
      occur if the mother has a medical condition requiring GC therapy (e.g. asthma) or
      if she threatens to deliver her baby prematurely. Synthetic GCs can readily cross
      the placenta and treatment is beneficial, at least in the short term, for
      maternal health and fetal survival. 3.Maternal stress during pregnancy can raise
      endogenous levels of the natural GC cortisol. A significant proportion of the
      cortisol is inactivated by the placental 'GC barrier'. However, exposure to
      severe stress during pregnancy can result in increased risk of miscarriage, low
      birth weight and behavioural deficits in children. 4.Animal studies have shown
      that excess exposure to both synthetic and natural GCs can alter normal organ
      development, including that of the heart, brain and kidney. The nature and
      severity of the organ impairment is dependent upon the timing of exposure and, in
      some cases, the type of GC used and the sex of the fetus. 5.In animal models,
      exposure to elevated GCs during pregnancy has been associated with adult-onset
      diseases, including elevated blood pressure, impaired cardiac and vascular
      function and altered metabolic function.

PMID- 22971054
TI  - Effect of carbon monoxide on bacteria-stimulated cytokine production by placental
      explants.
AB  - PROBLEM: Preterm birth is frequently caused by an inflammatory response to
      ascending infections of the reproductive tract. Carbon monoxide (CO) has potent
      anti-inflammatory properties at subtoxic concentrations. Whether or not CO can
      modulate inflammatory responses by placental tissues is unclear. METHODS:
      Placental explant cultures were incubated with heat-killed Escherichia coli or
      Ureaplasma parvum in the presence or absence of 250 ppm CO for 24 hr.
      Concentrations of cytokines relative viability of the cultures were quantified.
      RESULTS: Escherichia coli- and U. parvum-stimulated IL-1beta production was
      significantly inhibited by CO supplementation. Escherichia coli-stimulated, but
      not U. parvum-stimulated, IFN-gamma production was inhibited by CO. While CO
      inhibited PGE(2)  production by unstimulated cells, no effects on bacteria
      stimulated prostaglandin production were detected. CO had no effect on basal or
      E. coli-stimulated TNF-alpha production but enhanced TNF-alpha production by
      cultures stimulated with U. parvum. In addition, CO tended to improve the
      viability of the placental cultures. CONCLUSIONS: Low concentrations of CO tended
      to reduce proinflammatory cytokines and to promote the production of anti
      inflammatory cytokines in a pathogen-specific manner. These properties suggest
      that CO may be useful for promoting a pro-pregnancy cytokine milieu by placental
      explants and may reduce the consequences of intrauterine infections.

PMID- 22971053
TI  - How effective is effective enough? Opinions of potential end-users of
      microbicides from a rural South African community.
AB  - To assess the views of potential end-users of a microbicide in KwaZulu-Natal
      regarding the characteristics that would justify further development, three focus
      group discussions were conducted in 2009 with 23 local staff members working on a
      microbicide clinical trial, 20 former trial participants and 14 Community
      Advisory Board members not enrolled in the trial, in an area with high HIV
      incidence and low consistent condom use. All participants agreed on the need for
      additional HIV prevention options that are as effective as possible and can be
      used by women. The majority of respondents stated that even a highly acceptable
      HIV prevention option with protection as low as 30% would still be an important
      addition to condoms for women; that a partially protective microbicide would have
      to be introduced as part of the existing prevention messages in order to continue
      promoting condom use; that there should eventually be a choice between
      antiretroviral (ARV) and non-ARV-based microbicides and a choice of how and where
      to access microbicides. Respondents also felt it would be important to make plans
      for access to a microbicide that can offer protection, even if partial, rather
      than wait to find out if alternative microbicides are equally or more effective.
      Potential end-users in a high HIV prevalence area believe that a partially
      effective microbicide would be an important addition to the limited HIV
      prevention options for women. The significant challenges of introducing a
      partially protective HIV prevention option were recognised, but seen as ones
      worth facing, as well as an opportunity to lay the ground work for the
      introduction of more efficacious HIV prevention methods in the future.

PMID- 22971055
TI  - Epididymal cyst: not always a benign condition.

PMID- 22971057
TI  - Highly improved homopolymer aware nucleotide-protein alignments with 454 data.
AB  - BACKGROUND: Roche 454 sequencing is the leading sequencing technology for
      producing long read high throughput sequence data. Unlike most methods where
      sequencing errors translate to base uncertainties, 454 sequencing inaccuracies
      create nucleotide gaps. These gaps are particularly troublesome for translated
      search tools such as BLASTx where they introduce frame-shifts and result in
      regions of decreased identity and/or terminated alignments, which affect further
      analysis. RESULTS: To address this issue, the Homopolymer Aware Cross Alignment
      Tool (HAXAT) was developed. HAXAT uses a novel dynamic programming algorithm for
      solving the optimal local alignment between a 454 nucleotide and a protein
      sequence by allowing frame-shifts, guided by 454 flowpeak values. The algorithm
      is an efficient minimal extension of the Smith-Waterman-Gotoh algorithm that
      easily fits in into other tools. Experiments using HAXAT demonstrate, through the
      introduction of 454 specific frame-shift penalties, significantly increased
      accuracy of alignments spanning homopolymer sequence errors. The full effect of
      the new parameters introduced with this novel alignment model is explored.
      Experimental results evaluating homopolymer inaccuracy through alignments show a
      two to five-fold increase in Matthews Correlation Coefficient over previous
      algorithms, for 454-derived data. CONCLUSIONS: This increased accuracy provided
      by HAXAT does not only result in improved homologue estimations, but also
      provides un-interrupted reading-frames, which greatly facilitate further analysis
      of protein space, for example phylogenetic analysis. The alignment tool is
      available at http://bioinfo.ifm.liu.se/454tools/haxat.

PMID- 22971059
TI  - The prevention of exercise-induced bronchoconstriction: what are the options?

PMID- 22971058
TI  - Novel selective allosteric and bitopic ligands for the S1P(3) receptor.
AB  - Sphingosine 1-phosphate (S1P) is a lysophospholipid signaling molecule that
      regulates important biological functions, including lymphocyte trafficking and
      vascular development, by activating G protein-coupled receptors for S1P, namely,
      S1P(1) through S1P(5). Here, we map the S1P(3) binding pocket with a novel
      allosteric agonist (CYM-5541), an orthosteric agonist (S1P), and a novel bitopic
      antagonist (SPM-242). With a combination of site-directed mutagenesis, ligand
      competition assay, and molecular modeling, we concluded that S1P and CYM-5541
      occupy different chemical spaces in the ligand binding pocket of S1P(3). CYM-5541
      allowed us to identify an allosteric site where Phe263 is a key gate-keeper
      residue for its affinity and efficacy. This ligand lacks a polar moiety, and the
      novel allosteric hydrophobic pocket permits S1P(3) selectivity of CYM-5541 within
      the highly similar S1P receptor family. However, a novel S1P(3)-selective
      antagonist, SPM-242, in the S1P(3) pocket occupies the ligand binding spaces of
      both S1P and CYM-5541, showing its bitopic mode of binding. Therefore, our
      coordinated approach with biochemical data and molecular modeling, based on our
      recently published S1P(1) crystal structure data in a highly conserved set of
      related receptors with a shared ligand, provides a strong basis for the
      successful optimization of orthosteric, allosteric, and bitopic modulators of
      S1P(3).

PMID- 22971061
TI  - What is the current place of azoles in allergic bronchopulmonary aspergillosis
      and severe asthma with fungal sensitization.
AB  - Evaluation of: Chishimba L, Niven RM, Cooley J, Denning DW. Voriconazole and
      posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis
      and severe asthma with fungal sensitization. J. Asthma 49(4), 423-433 (2012).  
      Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by
      hypersensitivity to Aspergillus fumigatus that usually complicates the disease
      course of patients with asthma and cystic fibrosis. Oral corticosteroids are
      currently the treatment of choice for ABPA. Another active target is the use of
      azoles, which act by reducing the antigenic stimulus secondary to a decreased
      fungal burden. Studies suggest that itraconazole compared with placebo can
      improve symptoms in ABPA, decrease the immunological severity (IgE levels and
      total eosinophil counts), glucocorticoid requirement and the number of acute ABPA
      exacerbations. Severe asthma with fungal sensitization, a disorder closely
      related to ABPA, is a specific phenotype of asthma characterized by severe asthma
      and evidence of fungal sensitization after exclusion of ABPA. Again, oral
      itraconazole has been found to improve the quality of life in these steroid
      dependent asthma patients. The current retrospective study evaluated the use of
      newer azoles (voriconazole and posaconazole) in adult asthmatic patients with
      either ABPA or severe asthma with fungal sensitization, and found the newer
      azoles to improve asthma control and reduce the severity of ABPA.

PMID- 22971062
TI  - The COPD Assessment Test in the evaluation of chronic obstructive pulmonary
      disease exacerbations.
AB  - Evaluation of: Mackay AJ, Donaldson GC, Patel AR, Jones PW, Hurst JR, Wedzicha
      JA. Usefulness of the Chronic Obstructive Pulmonary Disease Assessment Test to
      evaluate severity of COPD exacerbations. Am. J. Respir. Crit. Care Med. 185(11),
      1218-1224 (2012).   The health status of patients with chronic obstructive
      pulmonary disease (COPD) is currently being assessed using several different
      questionnaires. One of them is the COPD Assessment Test (CAT), which is a quick
      and easy test for patients to complete and provides a score that indicates the
      impact of the disease on their health status. There is increasing evidence that
      the CAT is a promising tool to quantify COPD exacerbations. Accordingly, the CAT
      score can be a useful marker in clinical trials that evaluate the effectiveness
      of treatments in prevention or management of COPD exacerbations, or that
      investigate the disease progression over time. In the future, the CAT score could
      also be used as an outcome measure in clinical practice to track changes in
      patients' overall health status and to improve communication between patients and
      healthcare professionals.

PMID- 22971063
TI  - Technological advances in extracorporeal membrane oxygenation for respiratory
      failure.
AB  - Extracorporeal membrane oxygenation (ECMO) for neonatal and pediatric cardiac
      and/or respiratory failure is well established, and its use for adult respiratory
      failure is rapidly increasing. Management strategies developed over the past 30
      years coupled with significant recent technological advances have led to improved
      ECMO survival. These new technologies are expanding the potential applications
      for ECMO in exciting ways, including new patient populations and the ability to
      make ECMO mobile for both intra- and inter-hospital transport. In this article,
      we highlight some of the recent technological advances and their impact on the
      utilization of ECMO in increasingly diverse patient populations.

PMID- 22971064
TI  - Promising directions in the diagnosis of childhood tuberculosis.
AB  - Estimates of the burden of childhood tuberculosis have been hampered by the lack
      of a reliable diagnostic test. Clinical scoring systems, radiological findings
      and tuberculin skin testing (the traditional methods used for diagnosis) are
      unreliable, particularly in the era of HIV. Microbiologic confirmation using
      induced sputum is feasible and has become increasingly important to define the
      burden of disease and to enable appropriate treatment. The availability of a
      rapid molecular diagnostic test (Xpert(r) MTB/RIF; Cepheid) is an important
      advance that can improve case detection in children and enable rapid detection of
      mycobacterial drug resistance. Xpert testing of two induced sputum specimens
      detected approximately 75% of children with culture-confirmed disease. Urine
      lipoarabinomannan has shown promise as a rapid diagnostic in a subgroup of HIV
      infected severely immunocompromised adults, but there have been no data in
      children so far. Further research is needed to develop a rapid point-of-care,
      reliable and affordable diagnostic test for childhood tuberculosis that can be
      widely used.

PMID- 22971065
TI  - Asthma and mental health among youth: etiology, current knowledge and future
      directions.
AB  - Asthma and mental health problems, such as depression, anxiety and behavior
      disorders, are common among youth and are significant sources of morbidity. There
      is a consistent association between asthma and anxiety/depression and a less
      consistent association between asthma and behavior disorders. Possible biological
      and psychological mechanisms may include inflammatory processes as well as the
      stress of having to live with a life-threatening condition. Future studies are
      warranted with longitudinal designs to establish temporality as well as measures
      of potential confounds. Biological and psychological measures would complement
      the longitudinal design to further establish causality. In addition, more
      information on the degree to which asthma and mental health have reciprocal
      influences on each other over time - and the mechanisms of these relationships -
      are needed in order to develop more effective intervention strategies to improve
      asthma control and mental health among those with both.

PMID- 22971066
TI  - Current dilemmas in antimicrobial therapy in cystic fibrosis.
AB  - The majority of cystic fibrosis (CF)-related morbidity and mortality is caused by
      pulmonary damage due to recurrent and chronic infections. Considerable
      improvements in the survival of individuals with CF have been achieved in recent
      decades, some of which may be due to better management of common pathogens such
      as Staphylococcus aureus and Pseudomonas aeruginosa. While the search continues
      for the optimal approach for prophylaxis, eradication and maintenance treatment
      of infections, there are several unanswered questions, posing dilemmas related to
      various therapeutic choices. Microbes pose additional challenges by adapting to
      CF lungs and developing treatment resistance. Several new, highly antimicrobial
      resistant pathogens have emerged. Their pathogenic role in the progression of CF
      lung disease is not yet clear and effective treatment approaches have not been
      defined. There is an urgent need for well-designed comparative clinical trials of
      new antibiotic strategies.

PMID- 22971067
TI  - Targeting interleukins to treat severe asthma.
AB  - Severe asthma is thought to be a heterogeneous disease with different phenotypes
      predicated primarily on the nature of the inflammatory cell infiltrate and
      response to corticosteroid therapy. This group of patients often has refractory
      disease with an associated increase in morbidity and mortality, and there remains
      a need for better therapies for severe asthmatics. Inflammatory changes in asthma
      are driven by immune mechanisms, within which interleukins play an integral role.
      Interleukins are cell-signaling cytokines that are produced by a variety of
      cells, predominantly T cells. Knowledge about their actions has improved the
      understanding of the pathogenesis of asthma and provided potential targets for
      novel therapies. To date, this has not translated into clinical use. However,
      there are ongoing clinical trials that use monoclonal antibodies for various
      interleukins, some of which have shown to be promising in Phase II studies.

PMID- 22971068
TI  - The role of Helicobacter pylori infection in the development of allergic asthma.
AB  - Asthma is one of the most prevalent chronic diseases in developed countries, with
      steady increases in asthma prevalence evident, particularly in the last few
      decades. As genetic factors are unlikely to contribute to the rise in asthma
      prevalence, changes in lifestyle and exposure to environmental stimuli have been
      proposed to account for this trend. The 'disappearing microbiota' hypothesis
      postulates that major shifts in the human microbiome, resulting from dramatic
      lifestyle changes, account for the increase in asthma prevalence. In this
      context, persistent gastric colonization with the human-specific pathogen
      Helicobacter pylori has been negatively associated with the occurrence of asthma
      in epidemiological studies. In addition, experimental models of allergic airway
      disease revealed a direct link between infection with H. pylori and suppression
      of allergic airway disease through the induction of regulatory T cells. These and
      other new insights hold the promise of opening up new avenues toward the
      development of innovative, new strategies directed at asthma treatment and
      prevention.

PMID- 22971069
TI  - Respiratory viral and pneumococcal coinfection of the respiratory tract:
      implications of pneumococcal vaccination.
AB  - The interactions between Streptococcus pneumoniae and other respiratory pathogens
      have been studied in vitro, in animal models and in humans - including
      epidemiologic and vaccine probe studies. Interactions of pneumococcus with
      respiratory viruses are common, and many mechanisms have been suggested to
      explain this phenomenon. The aim of this review is to explore pneumococcal
      interactions with respiratory viruses and consider the potential role that the
      pneumococcal polysaccharide-protein conjugate vaccine may play in modifying
      pneumococcal-respiratory viral interactions.

PMID- 22971071
TI  - Cardiovascular reactivity and resistance to opposing viewpoints during intragroup
      conflict.
AB  - This study examined how the outcomes of joint decision making relate to
      cardiovascular reactions when group members disagree about the decision to be
      taken. A conflict was experimentally induced during a joint decision-making task,
      while cardiovascular markers of challenge/threat motivational states were
      assessed following the biopsychosocial model of challenge and threat (BPSM; J.
      Blascovich, 2008). Results show that individuals were less likely to adjust their
      initially preferred decision alternative the more they exhibited a cardiovascular
      pattern indicative of threat (i.e., relatively high total peripheral resistance
      and low cardiac output) compared to challenge. This finding extends the BPSM by
      showing a link between threat and rigidity, and emphasizes the importance of
      psychophysiological processes for studying intragroup conflict and decision
      making.

PMID- 22971072
TI  - Association of chitotriosidase genotype with the development of non-alcoholic
      fatty liver disease.
AB  - AIM:   Based on the role of chitotriosidase (CHIT-1) in the evolution of non
      alcoholic fatty liver disease, we explored whether CHIT-1 mutant allele plays a
      role in NAFLD progression. METHODS:   We genotyped 200 patients with NAFLD (110
      with non-alcoholic steatohepatitis [NASH] and 90 with simple steatosis) and 100
      control subjects. The chi(2) -test was performed for a case-control study. Odds
      ratios (OR) were adjusted for age, sex and body mass index (BMI) by using
      multiple logistic regression analysis with genotypes (additive model), age, sex
      and BMI as the independent variables. Multiple linear regression analysis was
      performed to test the independent effect of risk allele on clinical parameters
      while considering the effects of other variables (age, sex and BMI), which were
      assumed to be independent of the effect of the single nucleotide polymorphism.
      RESULTS:   The risk allele frequency of CHIT-1 wild type (Wt) was 0.71 in the
      control subjects, 0.77 in simple steatosis and 0.92 in patients with NASH. The OR
      (95% confidence interval) adjusted for age and BMI was 1.73. Multiple linear
      regression analysis indicated that the CHIT-1 Wt was significantly associated
      with increases in ferritin levels (P = 0.014) and the fibrosis stage (P = 0.011)
      in the patients with NASH, even after adjustment for age, sex and BMI,
      corroborating that the presence of the CHIT-1 Wt allele was an independent
      predictor of fibrotic NAFLD. In contrast, the steatosis grade was not associated
      with CHIT-1 mutant allele. CONCLUSION:   These findings suggest that a functional
      polymorphism in the CHIT-1 gene protects against NAFLD progression.

PMID- 22971073
TI  - Pattern of clinical genetics referral following perinatal postmortems.
AB  - Fetal loss can be spontaneous or induced following findings on the anomaly scan.
      This study aims to (1) ascertain referral rates and patterns of referral to
      clinical genetics (CG) triggered by postmortem (PM) findings and (2) improve the
      quality of care offered to those families at risk of recurrence. A review of all
      PM reports during 2007 and 2008 was undertaken. We collected clinical and
      demographic information on all those cases in which a recommendation for referral
      had been or should have been made. During the study period, 549 PMs were
      conducted, of which 72 (13%) had a recommendation for referral to CG. A further
      30 (5%) cases were identified in which a recommendation for referral to CG should
      have been made. Of the 72 cases with a recommendation for referral to CG, 54
      cases were identified within the catchment area. Of these, 29 (54%) resulted in a
      referral to Sheffield CG, with an average of 17 weeks' waiting time for referral.
      In >90% of cases it was possible to clarify diagnosis and offer additional
      information. A small proportion of families declined referral to CG. By mapping
      the process from PM report to potential referral to CG, we have been able to
      highlight areas of clinical concern and improve clinical practice. This study has
      also enabled us to gain a better understanding of the patient referral and
      clinical care pathways involved. This, in turn, has provided a clinical focus
      within the joint histopathology-genetics multidisciplinary meetings to enable
      discussion of potential referrals.

PMID- 22971074
TI  - Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and
      syncytin-1 in primary human trophoblasts.
AB  - BACKGROUND: The placental syncytiotrophoblast is the major source of maternal
      plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy.
      Placental CRH exerts multiple functions in the maternal organism: It induces the
      adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone,
      regulates the timing of birth via its actions in the myometrium and inhibits the
      invasion of extravillous trophoblast cells in vitro. However, the auto- and
      paracrine actions of CRH on the syncytiotrophoblast itself are unknown.
      Intrauterine growth restriction (IUGR) is accompanied by an increase in placental
      CRH, which could be of pathophysiological relevance for the dysregulation in
      syncytialisation seen in IUGR placentas. METHODS: We aimed to determine the
      effect of CRH on isolated primary trophoblastic cells in vitro. After CRH
      stimulation the trophoblast syncytialisation rate was monitored via syncytin-1
      gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in
      culture supernatant. The expression of the IUGR marker genes leptin and 11beta
      hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a
      period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce
      leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which
      are known features of IUGR. RESULTS: CRH did not influence the differentiation of
      isolated trophoblasts into functional syncytium as determined by beta-hCG
      secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH
      treatment significantly increased leptin and 11beta-HSD2 expression, as well as
      leptin secretion into culture supernatant after 48 h. CONCLUSION: The relevance
      of CRH for placental physiology is underlined by the present in vitro study. The
      induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might
      promote fetal nutrient supply and placental corticosteroid metabolism in the
      phase before labour induction.

PMID- 22971075
TI  - Oral health conditions and frailty in Mexican community-dwelling elderly: a cross
      sectional analysis.
AB  - BACKGROUND: Oral health is an important component of general well-being for the
      elderly. Oral health-related problems include loss of teeth, nonfunctional
      removable dental prostheses, lesions of the oral mucosa, periodontitis, and root
      caries. They affect food selection, speaking ability, mastication, social
      relations, and quality of life. Frailty is a geriatric syndrome that confers
      vulnerability to negative health-related outcomes. The association between oral
      health and frailty has not been explored thoroughly. This study sought to
      identify associations between the presence of some oral health conditions, and
      frailty status among Mexican community-dwelling elderly. METHODS: Analysis of
      baseline data of the Mexican Study of Nutritional and Psychosocial Markers of
      Frailty, a cohort study carried out in a representative sample of people aged 70
      and older residing in one district of Mexico City. Frailty was defined as the
      presence of three or more of the following five components: weight loss,
      exhaustion, slowness, weakness, and low physical activity. Oral health variables
      included self-perception of oral health compared with others of the same age;
      utilization of dental services during the last year, number of teeth, dental
      condition (edentate, partially edentate, or completely dentate), utilization and
      functionality of removable partial or complete dentures, severe periodontitis,
      self-reported chewing problems and xerostomia. Covariates included were gender,
      age, years of education, cognitive performance, smoking status, recent falls,
      hospitalization, number of drugs, and comorbidity. The association between
      frailty and dental variables was determined performing a multivariate logistic
      regression analysis. Final models were adjusted by socio-demographic and health
      factors RESULTS: Of the 838 participants examined, 699 had the information needed
      to establish the criteria for diagnosis of frailty. Those who had a higher
      probability of being frail included women (OR = 1.9), those who reported
      myocardial infarction (OR = 3.8), urinary incontinence (OR = 2.7), those who
      rated their oral health worse than others (OR = 3.2), and those who did not use
      dental services (OR = 2.1). For each additional year of age and each additional
      drug consumed, the probability of being frail increased 10% and 30%,
      respectively. CONCLUSIONS: Utilization of dental services and self-perception of
      oral health were associated with a higher probability of being frail.

PMID- 22971076
TI  - Evaluation of the effect of mycotoxin binders in animal feed on the analytical
      performance of standardised methods for the determination of mycotoxins in feed.
AB  - Recently, the use of substances that can suppress or reduce absorption, promote
      the excretion of mycotoxins or modify their mode of action in feed, so-called
      mycotoxin binders, has been officially allowed in the European Union as
      technological feed additives. The influence of the addition of mycotoxin binders
      to animal feed on the analytical performance of the official methods for the
      determination of mycotoxins was studied and the results are presented. Where
      possible standardised methods for analysis were applied. Samples of 20 commercial
      mycotoxin binders were collected from various companies. The following mycotoxins
      were included in the study: aflatoxin B1, deoxynivalenol, zearalenone, ochratoxin
      A, fumonisins B1 and B2, T-2 and HT-2 toxins. A binder (or binders combined in a
      group) was mixed with feed material containing the mycotoxin, and the feed
      material was analysed. For data evaluation, the mean values were compared by
      Student's t-test (an independent two-sample t-test with unequal sample sizes and
      equal variance). The repeatability standard deviation of each method was used as
      an estimate of method variability. No significant differences (p = 0.05) in
      mycotoxin levels between binder-free material and the material containing
      different binders were found. Further, the possible effects of binder addition in
      combination with processing (pelletising) on the amount of aflatoxin B1
      determined in feed were studied. Three commercial mycotoxin binders containing
      hydrated sodium calcium aluminosilicate (HSCAS) as the main component were used
      in these experiments. Feed samples with and without mycotoxin binders were
      pelletised with and without steam treatment. After pelletising, materials were
      analysed for AFB1. Only the combination pelletising and a mixture of binders
      added at a total level of 1.2% had a significant effect (41% reduction) on the
      amount of AFB1 determined.

PMID- 22971077
TI  - Meta-analysis of the effects of human disturbance on seed dispersal by animals.
AB  - Animal-mediated seed dispersal is important for sustaining biological diversity
      in forest ecosystems, particularly in the tropics. Forest fragmentation, hunting,
      and selective logging modify forests in myriad ways and their effects on animal
      mediated seed dispersal have been examined in many case studies. However, the
      overall effects of different types of human disturbance on animal-mediated seed
      dispersal are still unknown. We identified 35 articles that provided 83
      comparisons of animal-mediated seed dispersal between disturbed and undisturbed
      forests; all comparisons except one were conducted in tropical or subtropical
      ecosystems. We assessed the effects of forest fragmentation, hunting, and
      selective logging on seed dispersal of fleshy-fruited tree species. We carried
      out a meta-analysis to test whether forest fragmentation, hunting, and selective
      logging affected 3 components of animal-mediated seed dispersal: frugivore
      visitation rate, number of seeds removed, and distance of seed dispersal. Forest
      fragmentation, hunting, and selective logging did not affect visitation rate and
      were marginally associated with a reduction in seed-dispersal distance. Hunting
      and selective logging, but not fragmentation, were associated with a large
      reduction in the number of seeds removed. Fewer seeds of large-seeded than of
      small-seeded tree species were removed in hunted or selectively logged forests. A
      plausible explanation for the consistently negative effects of hunting and
      selective logging on large-seeded plant species is that large frugivores, as the
      predominant seed dispersers for large-seeded plant species, are the first animals
      to be extirpated from hunted or logged forests. The reduction in forest area
      after fragmentation appeared to have weaker effects on frugivore communities and
      animal-mediated seed dispersal than hunting and selective logging. The
      differential effects of hunting and selective logging on large- and small-seeded
      tree species underpinned case studies that showed disrupted plant-frugivore
      interactions could trigger a homogenization of seed traits in tree communities in
      hunted or logged tropical forests.

PMID- 22971078
TI  - 2D barcodes: a novel and simple method for denture identification.
AB  - Several methods of denture marking have been described in the literature.
      However, most of them are expensive, time-consuming, and do not permit the
      incorporation of large amounts of information. We propose a novel and simple
      method incorporating 2D codes which has several advantages over the existing
      methods. A 2D code was generated in the dental office and inserted into a
      maxillary denture. The code was then read using software downloaded into a mobile
      phone giving access to the website containing details about the patient. The
      denture was also subjected to durability tests, which did not hamper the efficacy
      of the 2D code. 2D coding for dentures is a simple, less expensive method with
      the potential of storing a large amount of information that can be accessed on
      site by the forensic investigator, thus allowing quick identification of the
      denture wearer.

PMID- 22971079
TI  - Optimization of L-DOPA production by Brevundimonas sp. SGJ using response surface
      methodology.
AB  - L-DOPA (3,4-dihydroxyphenyl-L-alanine) is an extensively used drug for the
      treatment of Parkinson's disease. In the present study, optimization of
      nutritional parameters influencing L-DOPA production was attempted using the
      response surface methodology (RSM) from Brevundimonas sp. SGJ. A Plackett-Burman
      design was used for screening of critical components, while further optimization
      was carried out using the Box-Behnken design. The optimized levels of factors
      predicted by the model were pH 5.02, 1.549 g l(-1) tryptone, 4.207 g l(-1) L
      tyrosine and 0.0369 g l(-1) CuSO(4) , which resulted in highest L-DOPA yield of
      3.359 g l(-1). The optimization of medium using RSM resulted in a 8.355-fold
      increase in the yield of L-DOPA. The anova showed a significant R(2) value
      (0.9667), model F-value (29.068) and probability (0.001), with insignificant lack
      of fit. The highest tyrosinase activity observed was 2471 U mg(-1) at the 18th
      hour of the incubation period with dry cell weight of 0.711 g l(-1). L-DOPA
      production was confirmed by HPTLC, HPLC and GC-MS analysis. Thus, Brevundimonas
      sp. SGJ has the potential to be a new source for the production of L-DOPA.

PMID- 22971081
TI  - Stabilizing ion and radical ion pair states in a paramagnetic endohedral
      metallofullerene/pi-extended tetrathiafulvalene conjugate.
AB  - Electron donor-acceptor conjugates of paramagnetic endohedral metallofullerenes
      and pi-extended tetrathiafulvalene (exTTF) were synthesized, characterized, and
      probed with respect to intramolecular electron transfer involving paramagnetic
      fullerenes. UV-vis-NIR absorption spectroscopy complemented by electrochemical
      measurements attested to weak electronic interactions between the electron donor,
      exTTF, and the electron acceptor, La@C(82), in the ground state. In the excited
      state, photoexcitation powers a fast intramolecular electron transfer to yield an
      ion and radical ion pair state consisting of one-electron-reduced La@C(82) and of
      one-electron-oxidized exTTF.

PMID- 22971080
TI  - Distinct mechanisms of calmodulin binding and regulation of adenylyl cyclases 1
      and 8.
AB  - Calmodulin (CaM), by mediating the stimulation of the activity of two adenylyl
      cyclases (ACs), plays a key role in integrating the cAMP and Ca(2+) signaling
      systems. These ACs, AC1 and AC8, by decoding discrete Ca(2+) signals can
      contribute to fine-tuning intracellular cAMP dynamics, particularly in neurons
      where they predominate. CaM comprises an alpha-helical linker separating two
      globular regions at the N-terminus and the C-terminus that each bind two Ca(2+)
      ions. These two lobes have differing affinities for Ca(2+), and they can interact
      with target proteins independently. This study explores previous indications that
      the two lobes of CaM can regulate AC1 and AC8 differently and thereby yield
      different responses to cellular transitions in [Ca(2+)](i). We first compared by
      glutathione S-transferase pull-down assays and offline nanoelectrospray
      ionization mass spectrometry the interaction of CaM and Ca(2+)-binding deficient
      mutants of CaM with the internal CaM binding domain (CaMBD) of AC1 and the two
      terminal CaMBDs of AC8. We then examined the influence of these three CaMBDs on
      Ca(2+) binding by native and mutated CaM in stopped-flow experiments to quantify
      their interactions. The three CaMBDs show quite distinct interactions with the
      two lobes of CaM. These findings establish the critical kinetic differences
      between the mechanisms of Ca(2+)-CaM activation of AC1 and AC8, which may
      underpin their different physiological roles.

PMID- 22971082
TI  - Sharp genetic discontinuity across a unimodal Heliconius hybrid zone.
AB  - Hybrid zones are powerful natural systems to study evolutionary processes to gain
      an understanding of adaptation and speciation. In the Cauca Valley (Colombia),
      two butterfly races, Heliconius cydno cydnides and Heliconius cydno weymeri, meet
      and hybridize. We characterized this hybrid zone using a combination of
      mitochondrial DNA (mtDNA) sequences, amplified fragment length polymorphisms
      (AFLPs), microsatellites and sequences for nuclear loci within and outside of the
      genomic regions that cause differences in wing colour pattern. The hybrid zone is
      largely composed of individuals of mixed ancestry. However, there is strong
      genetic discontinuity between the hybridizing races in mtDNA and, to a lesser
      extent, in all nuclear markers surveyed. The mtDNA clustering of H. c. cydnides
      with the H. cydno race from the Magdalena Valley and H. c. weymeri with the H.
      cydno race from the pacific coast suggests that H. c. cydnides colonized the
      Cauca Valley from the north, whereas H. c. weymeri did so by crossing the Andes
      in the southern part, implying a secondary contact origin. Colonization of the
      valley by H. cydno was accompanied by mimicry shift. Strong ecological isolation,
      driven by locally adaptive differences in mimetic wing patterns, is playing an
      important role in maintaining the hybrid zone. However, selection on wing pattern
      alone is not sufficient to explain the genetic discontinuity observed. There is
      evidence for differences in male mating preference, but the contribution of
      additional barriers needs further investigation. Overall, our results support the
      idea that speciation is a cumulative process, where the combination of multiple
      isolation barriers, combined with major phenotypic differences, facilitates
      population divergence in face of gene flow.

PMID- 22971083
TI  - System-based drug discovery within the human kinome.
AB  - INTRODUCTION: For well over a decade, significant effort has been devoted to the
      search for inhibitors of the human protein kinase family. This is increasingly
      translating into success in the clinic, with five new kinase inhibitor drugs
      approved since 2011. However, despite encouraging signs in other areas, success
      has been largely restricted to oncology. AREAS COVERED: This article reviews the
      prospects for kinase inhibitor drug discovery in oncology and other therapeutic
      areas. Major topics include the application of kinome profiling and lessons
      learned from kinase system-based research. With these fields nearing maturity,
      the validation of kinases as targets or their classification as liabilities is
      becoming increasingly pertinent. Other topics include a discussion of the
      properties required of good small molecule kinase probes. EXPERT OPINION: The
      tractability of protein kinases to small molecule discovery through system-based
      research is excellent, and adequate selectivity can often be achieved. With
      advances in screening methodology now enabling compound profiling across most of
      the kinome, researchers involved in drug discovery must decide what inhibition
      profiles are desirable. However, this assessment must be made on the basis of
      incomplete understanding of the disease biology of most kinases, and as a result
      there is a significant risk that drugs entering clinical trials will lack
      efficacy. Because of this, as well as greater effort to determine which kinases
      are therapeutically relevant for particular diseases, opportunities for quality
      pre-candidate compounds developed for specific indications to find alternative
      uses should be maximised by early screening through panels of phenotypic assays.

PMID- 22971084
TI  - Protonation of a peroxodiiron(III) complex and conversion to a diiron(III/IV)
      intermediate: implications for proton-assisted O-O bond cleavage in nonheme
      diiron enzymes.
AB  - Oxygenation of a diiron(II) complex, [Fe(II)(2)(MU-OH)(2)(BnBQA)(2)(NCMe)(2)](2+)
      [2, where BnBQA is N-benzyl-N,N-bis(2-quinolinylmethyl)amine], results in the
      formation of a metastable peroxodiferric intermediate, 3. The treatment of 3 with
      strong acid affords its conjugate acid, 4, in which the (MU-oxo)(MU-1,2
      peroxo)diiron(III) core of 3 is protonated at the oxo bridge. The core structures
      of 3 and 4 are characterized in detail by UV-vis, Mossbauer, resonance Raman, and
      X-ray absorption spectroscopies. Complex 4 is shorter-lived than 3 and decays to
      generate in ~20% yield of a diiron(III/IV) species 5, which can be identified by
      electron paramagnetic resonance and Mossbauer spectroscopies. This reaction
      sequence demonstrates for the first time that protonation of the oxo bridge of a
      (MU-oxo)(MU-1,2-peroxo)diiron(III) complex leads to cleavage of the peroxo O-O
      bond and formation of a high-valent diiron complex, thereby mimicking the steps
      involved in the formation of intermediate X in the activation cycle of
      ribonucleotide reductase.

PMID- 22971085
TI  - A phase 1 open-label trial shows that smad7 antisense oligonucleotide (GED0301)
      does not increase the risk of small bowel strictures in Crohn's disease.
AB  - BACKGROUND: In Crohn's disease (CD), knockdown of Smad7, an inhibitor of
      Transforming Growth Factor (TGF)-beta1 activity, with a specific antisense
      oligonucleotide (GED0301) seems to be safe and tolerable and associates with TGF
      beta1-mediated suppression of inflammatory pathways. AIM: Since TGF-beta1 has pro
      fibrogenic effects in many organs, we evaluated whether GED0301 treatment
      associates with the formation of small bowel strictures. METHODS: Fifteen
      patients with active, inflammatory CD, receiving oral GED0301 once daily for 7
      days, were monitored for the formation of small bowel strictures by Small
      Intestine Contrast Ultrasonography (SICUS). Serum basic fibroblast growth factor
      (bFGF) and human chitinase 3-like 1 (also known as YKL-40), two markers of CD
      related intestinal strictures, and matrix metalloproteinases (MMP) and tissue
      inhibitor 1 of MMPs (TIMP1) were analysed at day 0 and day 180 by ELISA. Crohn's
      disease activity index (CDAI) changes were also monitored. RESULTS: Fourteen
      patients completed the 6-month study; the remaining underwent intestinal
      resection for a severe relapse not responsive to medical treatment. No patient
      developed small bowel stricture and none experienced obstructive symptoms during
      the study period. GED0301 treatment induced no significant change in the
      circulating levels of bFGF, YKL-40, MMPs and TIMP1. Seven of 12 patients who
      reached clinical remission following GED0301 treatment maintained a CDAI < 150 at
      day 180. CONCLUSION: Short-term treatment of patients with Crohn's disease using
      GED0301 is not associated with the development of small bowel stricture, thus
      reinforcing the concept that this drug is safe at least at early time points.

PMID- 22971086
TI  - On-line changing of thinking about words: the effect of cognitive context on
      neural responses to verb reading.
AB  - Activity in frontocentral motor regions is routinely reported when individuals
      process action words and is often interpreted as the implicit simulation of the
      word content. We hypothesized that these neural responses are not invariant
      components of action word processing but are modulated by the context in which
      they are evoked. Using fMRI, we assessed the relative weight of stimulus features
      (i.e., the intrinsic semantics of words) and contextual factors, in eliciting
      word-related sensorimotor activity. Participants silently read action-related and
      state verbs after performing a mental rotation task engaging either a motor
      strategy (i.e., referring visual stimuli to their own bodily movements) or a
      visuospatial strategy. The mental rotation tasks were used to induce,
      respectively, a motor and a nonmotor "cognitive context" into the following
      silent reading. Irrespective of the verb category, reading in the motor context,
      compared with reading in the nonmotor context, increased the activity in the left
      primary motor cortex, the bilateral premotor cortex, and the right somatosensory
      cortex. Thus, the cognitive context induced by the preceding motor strategy-based
      mental rotation modulated word-related sensorimotor responses, possibly
      reflecting the strategy of referring a word meaning to one's own bodily activity.
      This pattern, common to action and state verbs, suggests that the context in
      which words are encountered prevails over the intrinsic semantics of the stimuli
      in mediating the recruitment of sensorimotor regions.

PMID- 22971087
TI  - Miniaturized and automated high-throughput verification of proteins in the ISET
      platform with MALDI MS.
AB  - A major bottleneck in high-throughput protein production is the validation step,
      which is why parallel and automated sample processing methods are highly
      desirable. Also, a miniaturized sample preparation format is preferred, as the
      reduction of reagent volumes significantly decreases the analysis cost per
      sample. We have developed an automated and miniaturized protein sequence
      verification protocol for recombinant proteins utilizing peptide mass
      fingerprinting and MS/MS analysis. The integrated selective enrichment target
      (ISET) platform, previously developed in our group, with its dual functionality,
      being both a sample preparation platform and a MALDI target plate, is employed.
      All steps including immobilized metal ion affinity chromatography  of protein on
      cobalt-loaded beads, tryptic digestion, and MALDI MS analysis are performed in an
      array format, without any sample transfers, on the same ISET chip. The automated
      configuration reduced the sample preparation time significantly. Starting with
      crude lysate, a full plate of 48 purified, digested samples prepared for MALDI-MS
      can be generated in 4 h, with only 30 min of operator involvement. This paper
      demonstrates the utility of the method by parallel analysis of 45 His-tagged
      human recombinant proteins.

PMID- 22971088
TI  - Associations between partner violence perpetration and history of STI among HIV
      infected substance using men in Russia.
AB  - Studies document a significant association between victimization from intimate
      partner violence (IPV) and sexually transmitted infections (STIs) and HIV among
      substance using women in Russia and elsewhere, but no study has examined IPV
      perpetration and STI among Russian men or HIV-infected men in Eastern Europe.
      This study was designed to assess the association between lifetime history of IPV
      perpetration and STI (lifetime and current) among substance using HIV-infected
      men in Russia. Cross-sectional analyses were conducted with baseline data from
      415 male participants enrolled in a randomized HIV intervention clinical trial
      [the HERMITAGE Study]. Participants were HIV-infected men reporting recent heavy
      alcohol use and unprotected sex in St. Petersburg, Russia. Baseline surveys
      assessed demographics, IPV perpetration, risk behaviors, and STI history. Current
      STI was assessed via blood testing for syphilis and urine testing for gonorrhea,
      Chlamydia and Trichomonas. Multiple logistic regression analyses were used to
      assess the association between history of IPV with lifetime and current STI.
      Participants were aged 20-57 years. Almost half of participants (46%) reported a
      history of IPV perpetration; 81% reported past 30-day binge alcohol use, and 43%
      reported past 30-day injection drug use. Past and current STI was 41% and 12%,
      respectively. Men reporting a history of IPV perpetration had significantly
      higher odds of reporting ever having an STI (AOR=1.6, 95% CI=1.1, 2.4) but lower
      odds of testing positive for a current STI (AOR=0.50, 95% CI=0.26, 0.96). These
      findings demonstrate that a history of male IPV perpetration is common in HIV
      infected Russian men and associated with a history of STI. Programmatic work
      toward IPV prevention is needed in Russia and may be beneficial in mitigating
      STIs, but more research is needed to understand how and why the association
      between IPV and STI changes over time in this population.

PMID- 22971090
TI  - Psychotropic drugs and risk of motor vehicle accidents: a population-based case
      control study.
AB  - AIM: To examine comprehensively the relationship between exposure to four classes
      of psychotropic drugs including antipsychotics, antidepressants, benzodiazepines
      (BZDs) and Z-drugs, and motor vehicle accidents (MVAs). METHOD: The authors
      conducted a matched case-control study of 5183 subjects with MVAs and 31 093
      matched controls, identified from the claims records of outpatient service visits
      during the period from 2000 to 2009. Inclusion criteria were defined as subjects
      aged equal to or more than 18 years and involved in MVAs. Conditional logistic
      regressions with covariates adjustment (including urbanity, psychiatric and non
      psychiatric outpatient visits and Charlson comorbidity score) were applied to
      examine the effect of four classes of psychotropic drugs on MVAs. RESULTS:
      Significant increased risk of MVAs was found in subjects taking antidepressants
      within 1 month (adjusted odds ratio (AOR) 1.73, 95% confidence interval (CI)
      1.34, 2.22), 1 week (AOR 1.71, 95% CI 1.29, 2.26), and 1 day (AOR 1.70, 95% CI
      1.26, 2.29) before MVAs occurred. Similar results were observed in subjects
      taking benzodiazepines (BZDs) (AOR 1.56, 95% CI 1.38, 1.75 for 1 month; AOR 1.64,
      95% CI 1.43, 1.88 for 1 week, and AOR 1.62, 95% CI 1.39, 1.88 for 1 day) and Z
      drugs (AOR 1.42, 95% CI 1.14, 1.76 for 1 month, AOR 1.37, 95% CI 1.06, 1.75 for 1
      week, AOR 1.34, 95% CI 1.03, 1.75 for 1 day), but not antipsychotics. Moreover,
      significant dose effects of antidepressants (equal to or more than 0.6-1.0 DDD),
      BZDs (equal to or more than 0.1-0.5 DDD) and Z-drugs (more than 1 DDD) were
      observed, respectively, on the risk of experiencing an MVA. CONCLUSION: Taken
      together, subjects taking antidepressants, BZDs and Z-drugs, separately, should
      be particularly cautioned for their increasing risk of MVAs.

PMID- 22971091
TI  - Genetic axonal neuropathies and neuronopathies of pre-natal and infantile onset.
AB  - The infantile-onset axonal neuropathies and neuronopathies are an uncommon and
      heterogeneous group of conditions causing weakness, wasting, and developmental
      delay in early childhood. Many are associated with central nervous system or
      other systemic manifestations and cause early mortality. We review the axonal
      Charcot-Marie-Tooth subtypes with onset in infancy, spinal muscular atrophy, and
      related syndromes of early infancy, giant axonal neuropathy, infantile
      neuroaxonal dystrophy, hereditary motor and sensory neuropathy with agenesis of
      the corpus callosum, early-onset neuropathies associated with mitochondrial
      disorders, and other less well-delineated clinical entities. Useful clinical and
      neuropathologic features in the diagnostic work-up of these conditions are also
      presented.

PMID- 22971092
TI  - Patterns of nerve injury and neuropathic pain in ischemic neuropathy after
      ligation-reperfusion of femoral artery in mice.
AB  - Ischemia is an important etiology of painful neuropathies. We generated a mouse
      system of ischemic neuropathy by ligation-reperfusion of the femoral artery to
      mimic neuropathic pain and nerve injury patterns observed clinically. Mice
      exhibited spontaneous neuropathic pain behaviors, which were most obvious after
      ischemia for 5 h. Mechanical and cold allodynia developed by post-operative day
      (POD) 7 and persisted through the experimental period up to POD 56. Neuropathic
      pain behaviors were alleviated with intraperitoneal gabapentin (50 and 100 mg/kg)
      in a dose-dependent manner. Large-fiber deficit assessed with nerve conduction
      studies was demonstrated by reduced amplitudes of the compound muscle action
      potential (CMAP) on POD 7 (48.4% of the control side, p < 0.001). Small-fiber
      impairment was demonstrated by decreased epidermal nerve density (END) on POD 7
      (29.1% of the control side, p < 0.001). Reductions in CMAP amplitudes and ENDs
      persisted through POD 56. Our system replicated the clinical manifestations of
      ischemic neuropathy: (1) neuropathic pain with cold and mechanical allodynia and
      (2) nerve injury to both large and small fibers with pathologic and physiologic
      evidence. This system produced by a simple procedure provides an opportunity to
      investigate mechanisms and further treatments of ischemic neuropathy on
      genetically engineered mice.

PMID- 22971093
TI  - Exogenous ciliary neurotrophic factor (CNTF) reduces synaptic depression during
      repetitive stimulation.
AB  - It has been shown that ciliary neurotrophic factor (CNTF) has trophic and
      maintenance effects on several types of peripheral and central neurons, glia, and
      cells outside the nervous system. Both CNTF and its receptor, CNTF-Ralpha, are
      expressed in the muscle. We use confocal immunocytochemistry to show that the
      trophic cytokine and its receptor are present in the pre- and post-synaptic sites
      of the neuromuscular junctions (NMJs). Applied CNTF (7.5-200 ng/ml, 60 min-3 h)
      does not acutely affect spontaneous potentials (size or frequency) or quantal
      content of the evoked acetylcholine release from post-natal (in weak or strong
      axonal inputs on dually innervated end plates or in the most mature singly
      innervated synapses at P6) or adult (P30) NMJ of Levator auris longus muscle of
      the mice. However, CNTF reduces roughly 50% the depression produced by repetitive
      stimulation (40 Hz, 2 min) on the adult NMJs. Our findings indicate that, unlike
      neurotrophins, exogenous CNTF does not acutely modulate transmitter release
      locally at the mammalian neuromuscular synapse but can protect mature end plates
      from activity-induced synaptic depression.

PMID- 22971094
TI  - PARP inhibitors attenuate chemotherapy-induced painful neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity of
      chemotherapy treatment for which no therapy is approved. Poly(ADP-ribose)
      polymerase (PARP)1/2 are nuclear enzymes activated upon DNA damage, and PARP1/2
      inhibition provides resistance against DNA damage. A role for PARP inhibition in
      sensory neurotransmission has also been established. PARP inhibitors attenuate
      pain-like behaviors and neuropathy-associated decreased peripheral nerve function
      in diabetic models. The hypothesis tested was that PARP inhibition protects
      against painful neuropathy. The objective of this study was to investigate
      whether the novel, selective PARP1/2 inhibitors (ABT-888 and related analogues)
      would attenuate development of mechanical allodynia in vincristine-treated rats.
      PARP inhibitors were dosed for 2 days, and then co-administered with vincristine
      for 12 days. Mechanical allodynia was observed in rats treated with vincristine.
      PARP1/2 inhibition significantly attenuated development of mechanical allodynia
      and reduced poly ADP-ribose (PAR) activation in rat skin. The data presented here
      show that PARP inhibition attenuates vincristine-induced mechanical allodynia in
      rats, and supports that PARP inhibition may represent a novel therapeutic
      approach for CIPN.

PMID- 22971095
TI  - A clinical pattern-based etiological diagnostic strategy for sensory
      neuronopathies: a French collaborative study.
AB  - Sensory neuronopathies (SNNs) encompass paraneoplastic, infectious, dysimmune,
      toxic, inherited, and idiopathic disorders. Recently described diagnostic
      criteria allow SNN to be differentiated from other forms of sensory neuropathy,
      but there is no validated strategy based on routine clinical investigations for
      the etiological diagnosis of SNN. In a multicenter study, the clinical,
      biological, and electrophysiological characteristics of 148 patients with SNN
      were analyzed. Multiple correspondence analysis and logistic regression were used
      to identify patterns differentiating between forms of SNNs with different
      etiologies. Models were constructed using a study population of 88 patients and
      checked using a test population of 60 cases. Four patterns were identified.
      Pattern A, with an acute or subacute onset in the four limbs or arms, early pain,
      and frequently affecting males over 60 years of age, identified mainly
      paraneoplastic, toxic, and infectious SNN. Pattern B identified patients with
      progressive SNN and was divided into patterns C and D, the former corresponding
      to patients with inherited or slowly progressive idiopathic SNN with severe
      ataxia and electrophysiological abnormalities and the latter to patients with
      idiopathic, dysimmune, and sometimes paraneoplastic SNN with a more rapid course
      than in pattern C. The diagnostic strategy based on these patterns correctly
      identified 84/88 and 58/60 patients in the study and test populations,
      respectively.

PMID- 22971096
TI  - Prediabetes/early diabetes-associated neuropathy predominantly involves sensory
      small fibres.
AB  - The aim of this study was to investigate the characteristics of prediabetes
      (preDM) and early (<3 years) diabetes mellitus type 2 (eDM2)-associated
      neuropathy and the value of recently proposed diagnostic criteria for diabetic
      sensorimotor polyneuropathy (DSPN). A prospective case-control study in a group
      of 48 consecutive patients with eDM2, 16 preDM patients and 40 age- and sex
      matched normoglycaemic controls was performed. Clinical and laboratory diagnostic
      tests were used to detect neuropathic abnormalities; these were further
      classified in terms of recent diagnostic criteria. Criteria for confirmed DSPN
      based on abnormal nerve conduction (NC) studies were met in 7 (14.6%) eDM2
      patients compared to no control (p < 0.05), and the proportion significantly
      increased to 37.5% compared to 2.5% controls (p < 0.001), if intraepidermal nerve
      fibre density (IENFD) was used as an alternative criterion in addition to NC. The
      subclinical DSPN criteria based on NC abnormalities were met in 4.2% eDM2
      patients, while the proportion of preDM and eDM2 cases with subclinical sensory
      small-fibre involvement documented by IENFD reached 12.5% and 22.9% compared with
      2.5% controls (p = 0.005 for eDM2). The absolute IENFD values from distal leg
      were significantly lower in both eDM2 (p < 0.0001) and preDM patients (p = 0.005)
      compared to controls. Neuropathy associated with preDM/eDM2 predominantly
      involves sensory small fibres.

PMID- 22971097
TI  - A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family.
AB  - We report the clinical, electrophysiological, and skin biopsy findings of an
      Italian Charcot-Marie-Tooth disease type 2 (CMT2) family with a novel
      heterozygous GDAP1 mutation. We observed a marked intra-familial phenotypic
      variability, in age at onset and disease severity which ranged from a typical CMT
      phenotype to an asymptomatic status. Electrophysiological study, consistent with
      an axonal sensory-motor neuropathy, confirmed a different degree of severity and
      disclosed minimal electrophysiological abnormalities also in the asymptomatic
      subjects. Skin biopsy findings showed a variable loss of large and small somatic
      nerve fibers. Molecular analysis identified a novel heterozygous missense
      mutation (Arg120Gly) in the GDAP1 gene which co-segregated with the disease
      within the pedigree. In conclusion, our findings confirm that the GDAP1 autosomal
      dominant mutations underlie a pronounced phenotypic variability, mimicking the
      effects of reduced penetrance. Notably, electrophysiological study in this family
      allowed to reveal hidden positive family history and assess a dominant
      inheritance pattern, revealing subclinical neuropathy in asymptomatic mutation
      carriers.

PMID- 22971098
TI  - Posterior reversible encephalopathy syndrome as the initial manifestation of
      Guillain-Barre syndrome: case report and review of the literature.
AB  - We report a 63-year-old female patient with Guillain-Barre syndrome revealed
      after posterior reversible encephalopathy syndrome. The onset was characterized
      by hypertension, headache, and cortical blindness, followed a few days later by
      progressive limb and facial paresis, dysautonomia, and respiratory failure.
      Treatment with plasmapheresis led to a rapid improvement of the clinical picture
      and the disappearance of magnetic resonance abnormalities. This report reviews
      the literature on this unusual association and discusses possible
      pathophysiological mechanisms.

PMID- 22971099
TI  - Autonomic nervous system involvement in a new CMT2B family.
AB  - We describe the first Italian family affected by CMT2B carrying a Val162Met
      substitution in the RAB7 gene. The clinical and electrophysiological features of
      our family are similar to those of previously reported families with RAB7
      mutations, also for the higher occurrence of ulcers in males. However, in this
      family we evaluated the autonomic nervous system, never investigated in CMT2B, by
      means of skin biopsy and sudomotor and cardiovascular tests. Our findings provide
      both pathological and functional evidence of autonomic nervous system involvement
      in CMT2B and expand the phenotypic characterization of CMT2B disease.

PMID- 22971101
TI  - Enzymatic synthesis of dilactone scaffold of antimycins.
AB  - Antimycins are a family of natural products possessing outstanding biological
      activities and unique structures, which have intrigued chemists for over a half
      century. The antimycin structural skeleton is built on a nine-membered dilactone
      ring containing one alkyl, one acyloxy, two methyl moieties, and an amide linkage
      connecting to a 3-formamidosalicylic acid. Although a biosynthetic gene cluster
      for antimycins was recently identified, the enzymatic logic that governs the
      synthesis of antimycins has not yet been revealed. In this work, the biosynthetic
      pathway for antimycins was dissected by both genetic and enzymatic studies for
      the first time. A minimum set of enzymes needed for generation of the antimycin
      dilactone scaffold were identified, featuring a hybrid nonribosomal peptide
      synthetase (NRPS)-polyketide synthase (PKS) assembly line containing both cis-
      and trans-acting components. Several antimycin analogues were further produced
      using in vitro enzymatic total synthesis based on the substrate promiscuity of
      this NRPS-PKS machinery.

PMID- 22971100
TI  - Quick, "imputation-free" meta-analysis with proxy-SNPs.
AB  - BACKGROUND: Meta-analysis (MA) is widely used to pool genome-wide association
      studies (GWASes) in order to a) increase the power to detect strong or weak
      genotype effects or b) as a result verification method. As a consequence of
      differing SNP panels among genotyping chips, imputation is the method of choice
      within GWAS consortia to avoid losing too many SNPs in a MA. YAMAS (Yet Another
      Meta Analysis Software), however, enables cross-GWAS conclusions prior to
      finished and polished imputation runs, which eventually are time-consuming.
      RESULTS: Here we present a fast method to avoid forfeiting SNPs present in only a
      subset of studies, without relying on imputation. This is accomplished by using
      reference linkage disequilibrium data from 1,000 Genomes/HapMap projects to find
      proxy-SNPs together with in-phase alleles for SNPs missing in at least one study.
      MA is conducted by combining association effect estimates of a SNP and those of
      its proxy-SNPs. Our algorithm is implemented in the MA software YAMAS.
      Association results from GWAS analysis applications can be used as input files
      for MA, tremendously speeding up MA compared to the conventional imputation
      approach. We show that our proxy algorithm is well-powered and yields valuable ad
      hoc results, possibly providing an incentive for follow-up studies. We propose
      our method as a quick screening step prior to imputation-based MA, as well as an
      additional main approach for studies without available reference data matching
      the ethnicities of study participants. As a proof of principle, we analyzed six
      dbGaP Type II Diabetes GWAS and found that the proxy algorithm clearly
      outperforms naive MA on the p-value level: for 17 out of 23 we observe an
      improvement on the p-value level by a factor of more than two, and a maximum
      improvement by a factor of 2127. CONCLUSIONS: YAMAS is an efficient and fast meta
      analysis program which offers various methods, including conventional MA as well
      as inserting proxy-SNPs for missing markers to avoid unnecessary power loss. MA
      with YAMAS can be readily conducted as YAMAS provides a generic parser for
      heterogeneous tabulated file formats within the GWAS field and avoids cumbersome
      setups. In this way, it supplements the meta-analysis process.

PMID- 22971102
TI  - Sepsis-associated liver injury: Incidence, classification and the clinical
      significance.
AB  - AIM:   Although it is a common complication of sepsis, sepsis-associated liver
      injury has not been substantially recognized, because its diagnostic criteria and
      clinical implications are unclear. We aimed to elucidate the incidence,
      manifestation, disease type classification and prognosis of sepsis-associated
      liver injury. METHODS:   The subjects were 588 patients admitted to our hospital
      for sepsis between 2001 and 2010. They were classified into "normal liver
      function", "sepsis-associated liver injury" and "sepsis-not-associated liver
      injury" groups. Sepsis-associated liver injury was classified as either
      "cholestatic", "hepatocellular" or "shock liver." Each of these three subgroups
      was further classified into "with jaundice" or "without jaundice". The primary
      end-point was the "poor prognosis ratio", defined as the proportion of patients
      whose prognosis was "unchanged", "worsened" or "died". RESULTS:   Among the 449
      subjects except for sepsis-not-associated liver injury (n = 139), the incidence
      of sepsis-associated liver injury was 34.7% (156/449), including 75 cholestatic
      (48.1%), 34 hepatocellular (21.8%) and 47 shock liver (30.1%) cases. Jaundice was
      a complication in 25 (33%), six (17.6%) and four (8.5%) patients in each group,
      respectively. The poor prognosis ratio was higher in males (37.5%) and in the
      elderly (47.7%); it was 48.0%, 38.2% and 62.8% in the cholestatic, hepatocellular
      and shock liver groups, respectively, and higher than the normal liver function
      (18.4%) group (P < 0.0001). It was also higher in patients with jaundice (68.6%)
      than in those without (45.5%) (P < 0.0001). CONCLUSION:   Sepsis-associated liver
      injury, especially with jaundice, is a significant predictive sign of poor
      prognosis in patients with sepsis.

PMID- 22971104
TI  - Flavonoids in the therapy and prophylaxis of flu: a patent review.
AB  - INTRODUCTION: Influenza viruses are common agents of flu outbreaks, epidemics,
      and pandemics that have occurred through the centuries. Prevention and control of
      flu are of great clinical importance, since they cause serious damage to health,
      with a consequent impact on quality of life and economy of a country. Resistance
      against the current drugs justifies the development of new anti-influenza
      molecules. Flavonoids exhibit significant activity against flu through their anti
      inflammatory and antiviral properties. The profile of these molecules makes them
      particularly promising as therapeutic agents against flu. AREAS COVERED: This
      review focus on the activity of flavonoids on different influenza virus targets
      as well as their use in patented pharmaceutical formulations. Twenty-one patents
      of these compounds for prophylaxis and treatment of influenza infection are
      discussed. EXPERT OPINION: The H1N1 influenza pandemic in 2009 resulted in a
      significant increase in the number of patents claiming pharmaceutical
      formulations for prophylaxis and treatment of flu. The research advances on
      flavonoids showing anti-influenza activity and the efforts made by researchers
      and industries consolidate the interest on new alternatives for the therapy of an
      infectious disease that represents a serious public health problem throughout the
      world.

PMID- 22971103
TI  - Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values
      in fission yeast DJ-1.
AB  - Cysteine residues with depressed pK(a) values are critical for the functions of
      many proteins. Several types of interactions can stabilize cysteine thiolate
      anions, including hydrogen bonds between thiol(ate)s and nearby residues as well
      as electrostatic interactions involving charged residues or dipoles. Dipolar
      stabilization of thiolates by peptide groups has been suggested to play a
      particularly important role near the N-termini of alpha-helices. Using a
      combination of X-ray crystallography, site-directed mutagenesis and spectroscopic
      methods, we show that the reactive cysteine residue (Cys111) in
      Schizosaccharomyces pombe DJ-1 experiences a 0.6 unit depression of its thiol
      pK(a) as a consequence of a hydrogen bond donated by a threonine side chain
      (Thr114) to a nearby peptide carbonyl oxygen at the N-terminus of an alpha-helix.
      This extended hydrogen bonded interaction is consistent with a sum of dipoles
      model whereby the distal hydrogen bond polarizes and strengthens the direct
      hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate).
      Therefore, our results suggest that the local dipolar enhancement of hydrogen
      bonds can appreciably stabilize cysteine thiolate formation. However, the
      substitution of a valine residue with a proline at the i + 3 position has only a
      minor effect (0.3 units) on the pK(a) of Cys111. As proline has a reduced peptide
      dipole moment, this small effect suggests that a more extended helix macrodipolar
      effect does not play a major role in this system.

PMID- 22971105
TI  - Common N1 and mismatch negativity neural evoked components are revealed by
      independent component model-based clustering analysis.
AB  - Mismatch negativity (MMN) is an event-related brain potential that appears when
      an auditory regularity is violated. Two main hypotheses have been proposed to
      explain it: the adaptation hypothesis and the memory-based hypothesis.
      Critically, they differ in whether the MMN can be distinguished from the N1. In
      this study, we assessed the differential contribution of the N1 and the MMN using
      independent component analysis (ICA) combined with model-based clustering. Our
      results show that the neural responses associated with the standard and deviant
      tones are explained by three clusters of reliable ICs with frontocentral scalp
      distribution. Two of these clusters exhibited a common N1 for both the standard
      and deviant tones and one cluster showed an enhancement of the anterior N1 at the
      MMN time range. These results support the adaptation hypothesis, which proposes
      that MMN is generated by neural mechanisms similar to those associated with
      auditory N1.

PMID- 22971106
TI  - The efficacy of ultrasound treatment as a reversible male contraceptive in the
      rhesus monkey.
AB  - BACKGROUND: The use of therapeutic ultrasound as a contraceptive approach has
      involved nonhuman primates as well as rats and dogs. The current study was
      undertaken to determine whether this treatment could be a method for reversible
      contraception, using a model with testes size similar to adult humans. METHODS:
      Two methods of ultrasound exposure were used, either the transducer probe at the
      bottom of a cup filled with saline (Cup) or direct application to the surface of
      the scrotum (Direct). Four adult rhesus (Macaca mulatta) males with normal semen
      parameters were treated with therapeutic ultrasound at 2.5 W/cm(2) for 30 min.
      Treatment was given 3 times, one every other day on a Monday-Wednesday-Friday
      schedule. For each male, semen quality was evaluated a minimum of three times
      over several months prior to ultrasound exposure and weekly for two months
      following ultrasound treatment. RESULTS: Semen samples from all males, regardless
      of exposure method, exhibited a decrease in the percentage of motile sperm
      following ultrasound treatment. There was an average reduction in motility of 40%
      the week following treatment. Similarly, curvilinear velocity and the percentage
      of sperm with a normally shaped flagellum were also reduced in all males
      following ultrasound treatment. A significant reduction in the total number of
      sperm in an ejaculate (total sperm count) was only observed in males that
      received ultrasound via the cup method. Following treatment via the cup method,
      males exhibited up to a 91.7% decrease in average total sperm count (n = 2).
      Sperm count did not approach pre-treatment levels until 8 weeks following
      ultrasound exposure. CONCLUSIONS: The sustained reduction in sperm count, percent
      motility, normal morphology, and sperm vigor with the cup exposure method
      provides proof of principle that testicular treatment with ultrasound can be an
      effective contraceptive approach in humans.

PMID- 22971107
TI  - Health systems frameworks in their political context: framing divergent agendas.
AB  - BACKGROUND: Despite the mounting attention for health systems and health systems
      theories, there is a persisting lack of consensus on their conceptualisation and
      strengthening. This paper contributes to structuring the debate, presenting
      landmarks in the development of health systems thinking against the backdrop of
      the policy context and its dominant actors. We argue that frameworks on health
      systems are products of their time, emerging from specific discourses. They are
      purposive, not neutrally descriptive, and are shaped by the agendas of their
      authors. DISCUSSION: The evolution of thinking over time does not reflect a
      progressive accumulation of insights. Instead, theories and frameworks seem to
      develop in reaction to one another, partly in line with prevailing paradigms and
      partly as a response to the very different needs of their developers. The reform
      perspective considering health systems as projects to be engineered is
      fundamentally different from the organic view that considers a health system as a
      mirror of society. The co-existence of health systems and disease-focused
      approaches indicates that different frameworks are complementary but not
      synthetic. The contestation of theories and methods for health systems relates
      almost exclusively to low income countries. At the global level, health system
      strengthening is largely narrowed down to its instrumental dimension, whereby
      well-targeted and specific interventions are supposed to strengthen health
      services and systems or, more selectively, specific core functions essential to
      programmes. This is in contrast to a broader conceptualization of health systems
      as social institutions. SUMMARY: Health systems theories and frameworks frame
      health, health systems and policies in particular political and public health
      paradigms. While there is a clear trend to try to understand the complexity of
      and dynamic relationships between elements of health systems, there is also a
      demand to provide frameworks that distinguish between health system
      interventions, and that allow mapping with a view of analysing their returns. The
      choice for a particular health system model to guide discussions and work should
      fit the purpose. The understanding of the underlying rationale of a chosen model
      facilitates an open dialogue about purpose and strategy.

PMID- 22971108
TI  - Placental membrane laminar necrosis and chorionic microcysts.

PMID- 22971110
TI  - Proteomics approaches for myeloid leukemia drug discovery.
AB  - INTRODUCTION: Global protein expression profiling between healthy vs diseased
      states helps identifying differential expression and post-translational
      modifications of proteins, thereby providing better insights into the molecular
      changes of disease diagnosis and prognosis. In addition, analytical separation
      and identification of proteins from complex mixtures can provide insight into
      targeted drug therapy and prediction of response to different therapeutics. AREAS
      COVERED: In the present review the authors summarize the readily available
      quantitative proteomics tools for the analytical separation and identification of
      target proteins in myeloid leukemia, AML in particular, and its future
      perspectives in its diagnostics and therapeutics. Within, the authors highlight
      some of the proteomics approaches such as gel-based quantitation strategies (2D,
      2D-DIGE); MS-based quantitative proteomics tools (metabolic labeling (SILAC),
      chemical labeling (ITRAQ, ICAT)); MS techniques (MALDI-MS/MS). In addition, some
      of the target proteins identified using proteomics approaches in myeloid leukemia
      are also discussed that may encourage cancer biology investigators to undertake
      proteomics as a vital tool in their study. EXPERT OPINION: With suitable,
      selective application of diverse set of quantitative proteomics strategies
      integrated with bioinformatics software and precise statistical analysis in
      myeloid leukemia holds tremendous promise in deciphering cancer proteome,
      understanding tumor pathophysiology and development of personalized molecular
      medicine and therapy.

PMID- 22971109
TI  - Exploring local immunological adaptation of two stickleback ecotypes by
      experimental infection and transcriptome-wide digital gene expression analysis.
AB  - Understanding the extent of local adaptation in natural populations and the
      mechanisms that allow individuals to adapt to their native environment is a major
      avenue in molecular ecology research. Evidence for the frequent occurrence of
      diverging ecotypes in species that inhabit multiple ecological habitats is
      accumulating, but experimental approaches to understanding the biological
      pathways as well as the underlying genetic mechanisms are still rare. Parasites
      are invoked as one of the major selective forces driving evolution and are
      themselves dependent on the ecological conditions in a given habitat.
      Immunological adaptation to local parasite communities is therefore expected to
      be a key component of local adaptation in natural populations. Here, we use next
      generation sequencing technology to compare the transcriptome-wide response of
      experimentally infected three-spined sticklebacks from a lake and a river
      population, which are known to evolve under selection by distinct parasite
      communities. By comparing overall gene expression levels as well as the
      activation of functional pathways in response to parasite exposure, we identified
      potential differences between the two stickleback populations at several levels.
      Our results suggest locally adapted patterns of gene regulation in response to
      parasite exposure, which may reflect different local optima in the trade-off
      between the benefits and the disadvantages of mounting an immune response because
      of quantitative differences of the local parasite communities.

PMID- 22971111
TI  - QSAR studies on imidazopyrazine derivatives as Aurora A kinase inhibitors.
AB  - Aurora kinases have emerged as attractive targets for the development of novel
      anti-cancer agents. A combined study of molecular docking, pharmacophore
      modelling and 3D-QSAR was performed on a series of imidazo [1, 2-a] pyrazines as
      novel Aurora kinase inhibitors to gain insights into the structural determinants
      and their structure-activity relationship. An ensemble of conformations based on
      molecular docking was used for PHASE pharmacophore studies. The developed best
      fitted pharmacophore model was validated by diverse chemotypes of Aurora A kinase
      inhibitors and was consistent with the structural requirements for the docked
      binding mechanism. Subsequently, the pharmacophore-based alignment was used to
      develop PHASE and comparative molecular similarity indices analysis (CoMSIA) 3D
      QSAR models. The best CoMSIA model showed good statistics (q (2 )= 0.567, r (2 )=
      0.992), and the predictive ability of the model was validated using an external
      test set of 13 compounds giving a satisfactory prediction ([Formula: see text]).
      The 3D contour maps provided insight into the binding mechanism and highlighted
      key structural features that are essential to the inhibitory activity. Based on
      the PHASE and CoMSIA 3D-QSAR results, a set of novel Aurora A inhibitors were
      designed that showed excellent potencies.

PMID- 22971112
TI  - Fluorescent polymer nanoparticle for selective sensing of intracellular hydrogen
      peroxide.
AB  - Fluorescent boronate-modified polyacrylonitrile (BPAN) nanoparticles of 50 nm
      diameter were fabricated for use as a selective H(2)O(2) sensor. The fluorescence
      intensity changed and an emission peak shifted when BPAN nanoparticles
      selectively interacted with H(2)O(2), relative to other reactive oxygen species
      (ROS). The BPAN nanoparticles undergo photoinduced electron transfer (PET)
      between a Schiff base moiety and boronate, which enhances the fluorescence and
      makes the nanoparticles suitable for selective ROS recognition. We demonstrate
      the use of these nanoparticles as a detector of endogenous H(2)O(2) produced in
      living cells. The representative features of the fluorescent BPAN nanoparticles
      that make them particularly attractive for H(2)O(2) and ROS detection are the
      following: they are easily synthesized as PET sensors; they exhibit a
      characteristic emission peak and peak shift that distinguishes reaction with
      H(2)O(2) from other ROS; and compared to organic compounds, the sensing moiety on
      BPAN polymer nanoparticles is more thermally stable and has superior mechanical
      properties, enabling their use in various biomedical applications.

PMID- 22971113
TI  - Cost analyses of peer health worker and mHealth support interventions for
      improving AIDS care in Rakai, Uganda.
AB  - A cost analysis study calculates resources needed to deliver an intervention and
      can provide useful information on affordability for service providers and policy
      makers. We conducted cost analyses of both a peer health worker (PHW) and a
      mHealth (mobile phone) support intervention. Excluding supervisory staffing
      costs, total yearly costs for the PHW intervention was $8475, resulting in a
      yearly cost per patient of $8.74, per virologic failure averted cost of $189, and
      per patient lost to follow-up averted cost of $1025. Including supervisory
      staffing costs increased total yearly costs to $14,991. Yearly costs of the
      mHealth intervention were an additional $1046, resulting in a yearly cost per
      patient of $2.35. In a threshold analysis, the PHW intervention was found to be
      cost saving if it was able to avert 1.50 patients per year from switching to
      second-line antiretroviral therapy. Other AIDS care programs may find these
      intervention costs affordable.

PMID- 22971114
TI  - Territorial user rights for fisheries as ancillary instruments for marine coastal
      conservation in Chile.
AB  - Territorial user rights for fisheries have been advocated as a way to achieve
      sustainable resource management. However, few researchers have empirically
      assessed their potential as ancillary marine conservation instruments by
      comparing them to no-take marine protected areas. In kelp (Lessonia trabeculata)
      forests of central Chile, we compared species richness, density, and biomass of
      macroinvertebrates and reef fishes among territorial-user-right areas with low
      level and high-level enforcement, no-take marine protected areas, and open-access
      areas in 42 100-m subtidal transects. We also assessed structural complexity of
      the kelp forest and substratum composition. Multivariate randomized permutation
      tests indicated macroinvertebrate and reef fish communities associated with the
      different access regimes differed significantly. Substratum composition and
      structural complexity of kelp forest did not differ among access regimes.
      Univariate analyses showed species richness, biomass, and density of
      macroinvertebrates and reef fishes were greater in highly enforced territorial
      user-right areas and no-take marine protected areas than in open-access areas.
      Densities of macroinvertebrates and reef fishes of economic importance were not
      significantly different between highly enforced territorial-user-right and no
      take marine protected areas. Densities of economically important
      macroinvertebrates in areas with low-level enforcement were significantly lower
      than those in areas with high-level enforcement and no-take marine protected
      areas but were significantly higher than in areas with open access. Territorial
      user-right areas could be important ancillary conservation instruments if they
      are well enforced.

PMID- 22971115
TI  - Quantification of the plasma clearance kinetics of a gadolinium-based contrast
      agent by photoinduced triplet harvesting.
AB  - The use of gadolinium-based contrast agents (GBCA) is integral to the field of
      diagnostic magnetic resonance imaging (MRI). Pharmacokinetic evaluation of the
      plasma clearance of GBCA is required for all new agents or improved formulations,
      to address concerns over toxicity or unforeseen side effects. Current methods to
      measure GBCA in plasma lack either a rapid readout or the sensitivity to measure
      small samples or require extensive processing of plasma, all obstacles in the
      development and characterization of new GBCA. Here, we quantify the plasma
      concentration of a labeled analogue of a common clinical GBCA by ligand triplet
      harvesting and energy transfer. The nonemittive GBCA becomes a "dark donor" to a
      fluorescent detector molecule, with a lower limit of detection of 10(-7) M in
      unprocessed plasma. On a time scale of minutes, we determine the plasma clearance
      rate in the wild-type mouse, using time-resolved fluorescence on a standard
      laboratory plate reader.

PMID- 22971116
TI  - Binding modes and functional surface of anti-mammalian scorpion alpha-toxins to
      sodium channels.
AB  - Scorpion alpha-toxins bind to the voltage-sensing domains of voltage-gated sodium
      (Na(V)) channels and interfere with the inactivation mechanisms. The functional
      surface of alpha-toxins has been shown to contain an NC-domain consisting of the
      five-residue turn (positions 8-12) and the C-terminus (positions 56-64) and a
      core-domain centered on the residue 18. The NC- and core-domains are
      interconnected by the linker-domain (positions 8-18). Here with atomistic
      molecular dynamics simulations, we examine the binding modes between two alpha
      toxins, the anti-mammalian AahII and the anti-insect LqhalphaIT, and the voltage
      sensing domain of rat Na(V)1.2, a subtype of Na(V) channels expressed in nerve
      cells. Both toxins are docked to the extracellular side of the voltage-sensing
      domain of Na(V)1.2 using molecular dynamics simulations, with the linker-domain
      assumed to wedge into the binding pocket. Several salt bridges and hydrophobic
      clusters are observed to form between the NC- and core-domains of the toxins and
      Na(V)1.2 and stabilize the toxin-channel complexes. The binding modes predicted
      are consistent with available mutagenesis data and can readily explain the
      relative affinities of AahII and LqhalphaIT for Na(V)1.2. The dissociation
      constants for the two toxin-channel complexes are derived, which compare
      favorably with experiment. Our models demonstrate that the functional surface of
      anti-mammalian scorpion alpha-toxins is centered on the linker-domain, similar to
      that of beta-toxins.

PMID- 22971117
TI  - Ranked retrieval of segmented nuclei for objective assessment of cancer gene
      repositioning.
AB  - BACKGROUND: Correct segmentation is critical to many applications within
      automated microscopy image analysis. Despite the availability of advanced
      segmentation algorithms, variations in cell morphology, sample preparation, and
      acquisition settings often lead to segmentation errors. This manuscript
      introduces a ranked-retrieval approach using logistic regression to automate
      selection of accurately segmented nuclei from a set of candidate segmentations.
      The methodology is validated on an application of spatial gene repositioning in
      breast cancer cell nuclei. Gene repositioning is analyzed in patient tissue
      sections by labeling sequences with fluorescence in situ hybridization (FISH),
      followed by measurement of the relative position of each gene from the nuclear
      center to the nuclear periphery. This technique requires hundreds of well
      segmented nuclei per sample to achieve statistical significance. Although the
      tissue samples in this study contain a surplus of available nuclei, automatic
      identification of the well-segmented subset remains a challenging task. RESULTS:
      Logistic regression was applied to features extracted from candidate segmented
      nuclei, including nuclear shape, texture, context, and gene copy number, in order
      to rank objects according to the likelihood of being an accurately segmented
      nucleus. The method was demonstrated on a tissue microarray dataset of 43 breast
      cancer patients, comprising approximately 40,000 imaged nuclei in which the HES5
      and FRA2 genes were labeled with FISH probes. Three trained reviewers
      independently classified nuclei into three classes of segmentation accuracy. In
      man vs. machine studies, the automated method outperformed the inter-observer
      agreement between reviewers, as measured by area under the receiver operating
      characteristic (ROC) curve. Robustness of gene position measurements to boundary
      inaccuracies was demonstrated by comparing 1086 manually and automatically
      segmented nuclei. Pearson correlation coefficients between the gene position
      measurements were above 0.9 (p < 0.05). A preliminary experiment was conducted to
      validate the ranked retrieval in a test to detect cancer. Independent manual
      measurement of gene positions agreed with automatic results in 21 out of 26
      statistical comparisons against a pooled normal (benign) gene position
      distribution. CONCLUSIONS: Accurate segmentation is necessary to automate
      quantitative image analysis for applications such as gene repositioning. However,
      due to heterogeneity within images and across different applications, no
      segmentation algorithm provides a satisfactory solution. Automated assessment of
      segmentations by ranked retrieval is capable of reducing or even eliminating the
      need to select segmented objects by hand and represents a significant improvement
      over binary classification. The method can be extended to other high-throughput
      applications requiring accurate detection of cells or nuclei across a range of
      biomedical applications.

PMID- 22971118
TI  - A randomized trial comparing the Ambu (r) Aura-i TM with the air-Q TM intubating
      laryngeal airway as conduits for tracheal intubation in children.
AB  - OBJECTIVES: To assess the clinical performance of the Ambu Aura-i (Aura-i) in
      children. AIM: To compare the Aura-i with the air-Q intubating laryngeal airway
      (air-Q) for the purposes of fiberoptic-guided tracheal intubation. BACKGROUND:
      The Aura-i is a new supraglottic airway designed for tracheal intubation.
      MATERIALS/METHODS: One hundred twenty children, ages 1 month to 6 years, were
      randomized to receive either the Aura-i or air-Q, and divided into three equal
      subgroups (Group 1, 2, 3) based on weight. The time for successful tracheal
      intubation was primarily assessed. The ease, time, and number of attempts for
      successful device insertion, leak pressures, fiberoptic grade of laryngeal view,
      number of attempts time for removal of the device after tracheal intubation, and
      complications were secondarily assessed. RESULTS: Device placement, tracheal
      intubation, and removal after tracheal intubation were successful in all
      patients. There were no differences in the time to successful tracheal intubation
      through the Aura-i (32.9 +/- 13.3 s), and the air-Q (33.9 +/- 13 s; P = 0.68), or
      fiberoptic grade of view between devices. There was not a statistically
      significant correlation between the time to intubation and the fiberoptic grade
      of laryngeal view in any of the groups. There were no statistically significant
      differences in the overall leak pressures, air-Q (18.3 +/- 6.1 cm H(2) O) vs Aura
      i (16 +/- 5.1 cm H(2) O; P = 0.05). In Group 1 (5-10 kg), leak pressures were
      higher with the air-Q (23.4 +/- 7.2 cm H(2) O) than the Aura-i (16.1 +/- 5.2 cm
      H(2) O; P = 0.001). There were no statistically significant differences in the
      time for removal between the two devices (P = 0.11). However, with the size 1.5
      Aura-i, the pilot balloon of the tracheal tube was removed in order to facilitate
      the removal of the device after tracheal intubation. CONCLUSIONS: Both devices
      served as effective conduits for fiberoptic-guided tracheal intubation. The
      limitation of the narrower proximal airway tube of the size 1.5 Aura-i should be
      considered if cuffed tracheal tubes are to be utilized.

PMID- 22971119
TI  - Future career plans of Malawian medical students: a cross-sectional survey.
AB  - BACKGROUND: Malawi has one of the lowest physician densities in the world, at 1.1
      doctors per 100,000 population. Undergraduate training of doctors at the national
      medical school has increased considerably in recent years with donor support.
      However, qualified doctors continue to leave the public sector in order to work
      or train abroad. We explored the postgraduate plans of current medical students,
      and the extent to which this is influenced by their background. METHODS: A self
      administered questionnaire was developed after discussion with students and
      senior staff. This included questions on background characteristics, education
      before medical school, and future career plans. This was distributed to all
      medical and premedical students on campus over 1 week and collected by an
      independent researcher. One reminder visit was made to each class. Chi-squared
      tests were performed to investigate the relationship of student characteristics
      with future career plans. RESULTS: One hundred and forty-nine students completed
      the questionnaire out of a student body of 312, a response rate of 48%. When
      questioned on their plans for after graduation, 49.0% of students plan to stay in
      Malawi. However, 38.9% plan to leave Malawi immediately. Medical students who
      completed a 'premedical' foundation year at the medical school were significantly
      more likely to have immediate plans to stay in Malawi compared to those who
      completed A-levels, an advanced school-leaving qualification (P = 0.037). Current
      premedical students were slightly more likely to have immediate plans to work or
      train in Malawi compared to medical students (P = 0.049). However, a trend test
      across all the years was not significant. When asked about future plans, nearly
      half of students intend to work or train outside Malawi. CONCLUSIONS: The
      majority of respondents plan to leave Malawi in the future. The effectiveness of
      the substantial upscaling of medical education in Malawi may be diminished unless
      more medical students plan to work in Malawi after graduation.

PMID- 22971120
TI  - Extensive blistering is a predictor for severe complications in children with
      mastocytosis.

PMID- 22971121
TI  - Therapeutic liver repopulation for metabolic liver diseases: Advances from bench
      to bedside.
AB  - Metabolic liver diseases are characterized by inherited defects in hepatic
      enzymes or other proteins with metabolic functions. Therapeutic liver
      repopulation (TLR), an approach of massive liver replacement by transplanted
      normal hepatocytes, could be used to provide the missing metabolic function
      elegantly. However, partial and transient correction of the underlying metabolic
      defects due to very few integrated donor cell mass remains the major obstacle for
      the effective and widespread use of this approach. Little engraftment and
      proliferation insufficiency lead to the poor outcome. This article reviews the
      advances in the mechanisms of initial engraftment and selective proliferation and
      suggests some effective treatment strategies, from pharmacological
      preconditioning to stem cell transplantation, to optimize liver repopulation with
      liver cell transplantation. Enhancing cell viability and plating efficiency,
      increasing sinusoidal spaces, regulation of sinusoidal endothelial cell barrier
      and controlling inflammatory reaction may promote initial cell engraftment. Liver
      directed irradiation, reversible portal vein embolization and fetal liver
      stem/progenitor cell transplantation induce preferential proliferation of donor
      cells substantially without severe side-effects. Furthermore, it seems better to
      use combined approaches to achieve a high level of liver repopulation for the
      management of metabolic liver diseases.

PMID- 22971122
TI  - Exploring the underlying factors influencing e-learning adoption in nurse
      education.
AB  - AIMS: To report a study undertaken to explore the underlying factors influencing
      e-learning adoption in nurse education. BACKGROUND: Despite e-learning's high
      profile it has not been readily integrated into teaching practice in nurse
      education. Previous research has identified generic, cross-disciplinary factors
      but has left out 'soft' factors. DESIGN: The study adopted an exploratory
      descriptive design. METHODS: Q-methodology was used to explore e-learning
      adoption in a Division of Nursing located in an institution of Higher Education
      in the UK. Between September-December 2009, 38 participants were recruited to
      participate in Q-sorts and post-sort interviews. The Q-sort data were factor
      analysed and the interviews were coded to their respective factors to develop in
      depth narratives. FINDINGS: Four factors were identified: 'E-learning advocates'
      saw e-learning's potential to improve nurse education and prepare future nurses
      for their evolving role; the 'Humanists' had avoided e-learning because they
      valued human interaction; the 'Sceptics' doubted that technology could improve
      learning outcomes; and the 'Pragmatics,' only used e-learning as a tool to post
      lecture notes online to supplement what they covered in class. CONCLUSION: The
      findings point to the variety of responses existing among nurse academics faced
      with integrating e-learning into their teaching. Moving beyond the binary labels
      commonly attributed to those considered either 'early adopters' or 'laggards,'
      the findings contribute to the literature by revealing a wider breadth of views
      and responses towards technology. Acknowledging these views can inform future e
      learning strategies and lead to improvement in e-learning use in nurse education.

PMID- 22971125
TI  - Identification of tool marks of a sickle on a telephone cable.
AB  - Linkage of a cutting tool (a sickle) with a telephone cable of 100 pairs of
      copper wires is reported in a case of theft of a telephone cable. Telephone
      cables contain numerous insulated copper wires of small diameter inside an outer
      covering and are stolen for the relatively precious copper. The cutting pattern
      of the cable can only point to the type of the tool but because of the large
      number of copper wires, it is practically difficult to make a definite linkage
      with the tool used to cut the cable by comparing the tool marks. The present work
      reports the successful attempt of the authors in establishing a definite linkage
      of a stolen telephone cable with a sickle recovered from the suspects. Spot
      microchemical test was performed for detection of copper on the blade of the
      sickle, and then tool mark comparison was performed to link the tool marks on the
      metal strip inside the outer covering of the cable to the blade of the sickle.

PMID- 22971123
TI  - Editorial Comment to chyluria after partial nephrectomy: a rare but considerable
      complication.

PMID- 22971126
TI  - Hospital factors and patient characteristics in the treatment of colorectal
      cancer: a population based study.
AB  - BACKGROUND: The present study focuses on the analysis of social, clinical and
      hospital characteristics that can lead to disparities in the management and
      outcome of care. To that end, indicators of the quality of initial treatment
      delivered to newly-diagnosed colorectal cancer patients in a North-Western Region
      of Italy, were investigated using administrative data. METHODS: The cohort
      includes all incident colorectal cancer patients (N = 24,187) selected by a
      validated algorithm from the Piedmont Hospital Discharge Record system over an 8
      year period (2000-2007).Three indicators of quality of care in this population
      based cohort were evaluated: the proportion of preoperative radiotherapy (RT) and
      of abdominoperineal (AP) resection in rectal cancer patients, and the proportion
      of postoperative in-hospital mortality in colorectal cancer patients. RESULTS:
      Among rectal cancers, older patients were less likely to have preoperative RT,
      and more likely to receive an AP resection compared to younger patients. The
      probability of undergoing preoperative RT and AP resection was reduced in females
      compared to males (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.64-0.93
      and OR 0.78, 95%CI 0.69-0.89, respectively). However, there was a trend of
      increasing RT over time (p for trend <0.01). The probability of undergoing AP
      resection was increased in less-educated patients and in hospitals with a low
      caseload.A higher risk of postoperative in-hospital mortality was found among
      colorectal cancer patients who were older, male, (female versus male OR 0.71,
      95%CI 0.60-0.84), unmarried (OR 1.32, 95%CI 1.09-1.59) or with unknown marital
      status. CONCLUSIONS: The study provides evidence of the importance of social,
      clinical and hospital characteristics on the equity and quality of care in a
      Southern European country with an open-access public health care system.

PMID- 22971127
TI  - Quality of life impact of external beam radiotherapy for advanced thyroid
      carcinoma.
AB  - BACKGROUND: External beam radiotherapy (XRT) has an established role in the
      management of recurrent or advanced well-differentiated thyroid carcinoma (WDTC).
      The goal of this study was to investigate the impact of this additional
      intervention on the quality of life (QOL) compared with total thyroidectomy (TT),
      with or without adjuvant radioactive iodine (RAI). METHODS: A cross-sectional
      analysis using validated QOL instruments was performed. Patients receiving XRT
      between 1992 and 2008 for WDTC were identified and offered study participation.
      The Quality of Life Radiation Therapy Instrument and the Head and Neck Companion
      Module were administered retrospectively (N=13). For a comparison, patients
      previously treated with TT (N=11) alone as well as TT with postoperative RAI
      (N=11) for WDTC were also evaluated. RESULTS: Thirty-four patients were included
      in the analysis. The XRT group reported significant decreases in chewing,
      swallowing, and appetite, and significant increase in pain, compared with both
      the RAI group and the TT group. Significant differences were reported for
      questions with regard to peace of mind, feeling discouraged, saliva, taste,
      ability to eat regular food, and concerns for the appearance of the neck in both
      RAI and XRT groups compared with TT patients. Subscale analysis of head and neck
      specific questions demonstrated significant overall differences for both RAI and
      XRT groups compared with thyroidectomy alone, with no differences observed
      between RAI and XRT groups in a direct comparison. CONCLUSIONS: RAI therapy
      results in a measurable decrease in head and neck specific QOL measures compared
      with TT alone. The addition of XRT results in additional measurable morbidity
      secondary to pain and dysphagia.

PMID- 22971128
TI  - Artemisinin derivatives: a patent review (2006 - present).
AB  - INTRODUCTION: The isolation of artemisinin from an ancient Chinese remedy in the
      early 1970s heralded the beginning of a new era in antimalarial drug therapy
      culminating in artemisinin-based combination therapies currently being the
      mainstay of malaria treatment worldwide. Ongoing research on this compound and
      its derivatives has revealed its potential use in treating other infectious and
      noninfectious diseases. AREAS COVERED: This review provides a summary of patents
      published globally from January 2006 to June 2012 covering promising artemisinin
      derivatives and artemisinin-based drug combinations developed for use in various
      therapeutic areas. EXPERT OPINION: The diversity of semi-synthetic artemisinin
      derivatives has been limited to the same design strategy of modifying the
      artemisinin molecule at the same positions due to inherent synthetic challenges.
      To address this, future endeavors should include: the use of biotransformation
      strategies to modify other positions in the sesquiterpene ring while retaining
      the endoperoxide bridge; the design and synthesis of synthetic ozonides based on
      the pharmacophoric endoperoxide motif and drug repositioning approaches to
      artemisinin-based combination therapy. A better understanding of the mechanism of
      action of artemisinin derivatives and their biomolecular targets may provide an
      invaluable tool for the development of derivatives with a wider array of activity
      and greater clinical utility than currently appreciated.

PMID- 22971130
TI  - Successful administration of intranasal glucagon in the out-of-hospital
      environment.
AB  - We present a case of successful prehospital treatment of hypoglycemia with
      intranasal (IN) glucagon. Episodes of hypoglycemia can be of varying severity and
      often requires quick reversal to prevent alteration in mental status or
      hypoglycemic coma. Glucagon has been shown to be as effective as glucose for the
      treatment of hypoglycemia. The inability to obtain intravenous (IV) access often
      impairs delivery of this peptide and is therefore frequently given via the
      intramuscular (IM) route. Intranasal administration of glucagon has been shown to
      be as effective as the IV route and may be used for rapid correction of
      hypoglycemic episodes where IV access is difficult or unavailable and IM
      administration is undesirable. We describe the first documentation in the peer
      reviewed literature of the successful treatment and reversal of an insulin
      induced hypoglycemic episode with IN glucagon in the prehospital setting. We also
      present a review of the literature regarding this novel medication administration
      route.

PMID- 22971132
TI  - Deficiency in the nuclear-related factor erythroid 2 transcription factor (Nrf1)
      leads to genetic instability.
AB  - Nuclear factor erythroid-derived 2-related factor 1 (Nrf1) regulates cellular
      stress response genes, and has also been suggested to play a role in other
      cellular processes. We previously demonstrated that hepatocyte-specific deletion
      of Nrf1 in mice resulted in spontaneous apoptosis, inflammation, and development
      of liver tumors. Here, we showed that both fibroblasts derived from Nrf1 null
      mouse embryos and fibroblasts expressing a conditional Nrf1 allele showed
      increased micronuclei and formation of abnormal nuclei. Lentiviral shRNA-mediated
      knockdown of Nrf1 in SAOS-2 cells also resulted in increased micronuclei,
      abnormal mitosis and multi-nucleated cells. Metaphase analyses showed increased
      aneuploidy in Nrf1(-/-) embryonic fibroblasts. Nuclear defects in Nrf1-deficient
      cells were associated with decreased expression of various genes encoding
      kinetochore and mitotic checkpoint proteins. Our findings suggest that Nrf1 may
      play a role in maintaining genomic integrity, and that Nrf1 dysregulation may
      induce tumorigenesis.

PMID- 22971133
TI  - Risk-spreading larviposition behaviour of female nose bot flies (Cephenemyia)
      attacking black-tailed deer.
AB  - While baited deer models were under observation nine Cephenemyia jellisoni
      Townsend (Diptera: Oestridae) females and seven C. apicata Bennett & Sabrosky
      engaged in a risk-spreading larviposition behaviour by larvipositing on models
      only once and then flying away. Additionally, analysis of 225 unobserved
      larvipostions in which larvae were trapped in adhesive on the muzzles of deer
      models showed that 94% of C. apicata and 95% of C. jellisoni larviposited on a
      model only once. The number of single larvipositions was highly significant for
      both species. The principal adaptive significance of such risk-spreading
      larviposition behaviour is that it spreads the reproductive output of a female
      among many hosts, and in years when adult eclosion and survival rates are low, it
      ensures that the larvae of the few surviving females will be distributed among a
      maximum number of hosts. Several other benefits of such behaviour also are
      discussed.

PMID- 22971135
TI  - What do network members know? Network members as reporters of depression among
      Caucasian-American and African-American older women.
AB  - OBJECTIVE: To determine whether family members and friends can be accurate
      reporters of depression in older women and whether their reports predict
      diagnostic depression concurrently and across a one-year time interval. METHOD:
      African-American and Caucasian older women (N = 153; mean age = 75) previously
      screened for depression nominated network members (NMs) who could be contacted as
      informants. NMs completed an informant version of the CES-D, described their
      closeness to the participant, the extent of the participant's support from family
      and friends, and their assessment of the participant's typical coping strategies.
      These reports were then used to predict participant CES-D, Hamilton depression
      scores, and Structured Clinical Interview (SCID) depression diagnoses
      concurrently and at six-month and one-year intervals. RESULTS: NMs' estimates of
      participants CES-D status were highly correlated with participants own CES-D
      scores, and also predicted Hamilton depression scores and SCID diagnoses
      concurrently and at six months and one year later. NMs' ratings of participants'
      use of positive coping also predicted depression at six months and one year.
      CONCLUSION: NMs knew when elderly women were depressed and their reports were
      accurate predictors of depression even one year later, which implies that elderly
      depression does not abate spontaneously. Future research should test the
      possibility that family and friends might be recruited as allies in encouraging
      earlier treatment and in providing support to older adults through difficult life
      transitions.

PMID- 22971134
TI  - Racial differences in the relationship between tobacco dependence and nicotine
      and carcinogen exposure.
AB  - AIMS: To investigate the relationships between tobacco dependence, biomarkers of
      nicotine and carcinogen exposure and biomarkers of nicotine and carcinogen
      exposure per cigarette in back and white smokers. DESIGN, SETTING AND
      PARTICIPANTS: A total of 204 healthy black (n = 69) and white (n = 135) smokers
      were enrolled into two clinical studies. MEASUREMENT: Nicotine equivalents
      (nicotine and its metabolites), 4-(methylnitrosamino)-1-(3)pyridyl-1-butanol
      (NNAL) and polycyclic aromatic hydrocarbon (PAH) metabolites were measured in
      urine. The Fagerstrom Test for Nicotine Dependence (FTND) and time to first
      cigarette (TFC) measured tobacco dependence. FINDINGS: Average TFC and FTND for
      blacks and whites were not significantly different. Urine NNAL and nicotine
      equivalents increased with increasing FTND in whites but did not increase in
      blacks (race * FTND interaction, both P < 0.031). The interaction term was not
      significant for PAHs. An inverse relationship was seen between FTND and nicotine
      equivalents, NNAL and PAH metabolites per cigarette in blacks but remained flat
      in whites (race * FTND interaction, all P <= 0.039). Regardless of dependence
      (low dependence, TFC >15 minutes; high dependence, TFC <=15 minutes), FTND and
      TFC were not correlated significantly with urine nicotine equivalents and
      carcinogen exposure in blacks. We found moderate correlations between FTND and
      TFC and nicotine equivalents and carcinogen exposure among whites of low
      dependence and non-significant correlations among whites of high dependence.
      CONCLUSION: In the United States, tobacco dependence measures were related
      linearly to nicotine intake and carcinogen exposure in white but not in black
      smokers. The relationship between dependence measures and tobacco biomarkers in
      black smokers regardless of level of dependence resembled highly dependent white
      smokers.

PMID- 22971136
TI  - Short- and long-term prognostic value of the TIMI risk score after primary
      percutaneous coronary intervention for ST-segment elevation myocardial
      infarction.
AB  - OBJECTIVES: We investigated the short- and long-term predictive value of the TIMI
      risk score regarding mortality for patients treated with primary percutaneous
      coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI).
      BACKGROUND: Data on the long-term predictive value of the TIMI risk score is
      sparse. METHODS: We used data from 3,609 STEMI patients undergoing PPCI in a high
      volume PCI center in The Netherlands. Cumulative event rates according to TIMI
      score variables were estimated with the Kaplan-Meier method and compared with the
      log-rank test. The original TIMI risk score was modified based on the
      availability of the data in the single center registry. RESULTS: Higher TIMI
      scores were associated with significantly higher mortality at short- and long
      term follow-up (P < 0.001 for both). Age and Killip Class IV at presentation were
      significant predictors for both short- and long-term mortality. Patients with an
      anterior MI, heart frequence >100 beats per minute, or systolic blood pressure
      <100 mmHG had a worse short-term prognosis compared to those who had not.
      However, long-term mortality was nonsignificantly different. The presence of a
      history of diabetes/hypertension and weight had only long-term prognostic value.
      Time to PPCI did not have any prognostic value. CONCLUSIONS: Our current report
      shows that the TIMI risk score has both short- and long-term discriminative
      value. The different variables contained in the TIMI risk score predict short
      term prognosis, others predominantly long-term mortality, whereas some are
      predictive for both.

PMID- 22971137
TI  - One-pot synthesis of pyrrolo[1,2-a]quinoxaline derivatives via iron-promoted aryl
      nitro reduction and aerobic oxidation of alcohols.
AB  - Here, we describe a new one-pot method to synthesize 4,7-substituted pyrrolo[1,2
      a]quinoxalines and related heterocyles through a cascade of redox reactions/imine
      formation/intramolecular cyclization. This procedure tolerates readily available
      substituted 1-(2-nitrophenyl)pyrrole derivatives and aliphatic or benzylic
      alcohols as starting materials using iron powder and acidic conditions. This is
      the first example of constructing N-heterocycles via iron-mediated aryl nitro
      reduction and aerobic oxidation of alcohols in one pot.

PMID- 22971138
TI  - Cytochrome P450 (CYP3A4*18) and glutathione-S-transferase (GSTP1) polymorphisms
      in a healthy Tunisian population.
AB  - AIM: Human cytochrome P450 3A and glutathione S-transferase (GST) enzymes evolved
      to catalyze the metabolism of numerous common therapy drugs and endogenous
      molecules. Members of the CYP3A are the majority expressed in human liver and
      intestine. The genetic factors play an important role in the interindividual
      variability in CYP3A and GST activity. Detection of CYP3A4 and GST variant
      alleles and knowledge about their allelic frequency in specific ethnic groups are
      important to lead to individualized drug dosing and improved therapeutics.
      METHODS: We determined the allelic frequency of the CYP3A4*18 and GSTP1 in a
      group of 138 healthy Tunisian subjects using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) assays. It is based on a
      specific PCR product cut by restriction endonucleases. This method offers the
      advantage of cutting DNA by the appropriate restriction enzyme at the correct
      mutation site hence enhancing its reliability. Electrophoretic separation
      demonstrates the presence (or absence) of restriction sites. RESULTS: In the
      group of 138 unrelated individuals, the frequencies of the CYP3A4*18 and GSTP1
      variant allele in this Tunisian population were 0.02 and 0.01, respectively.
      CONCLUSIONS: The present study describes polymorphisms of Cyp3A4 and GST among
      Tunisian subjects. We developed a simple assay for the detection of the CYP3A4*18
      and GSTP1 polymorphisms and we compared our allelic frequencies to other
      populations. No significant difference was obtained. This study provides the
      first analysis of CYP3A4*18 and GSTP1 mutant allele frequencies in the Tunisian
      population.

PMID- 22971139
TI  - The association between levels of tissue inhibitor of metalloproteinase-1 with
      acute heart failure and left ventricular dysfunction in patients with ST
      elevation myocardial infarction treated by primary percutaneous coronary
      intervention.
AB  - AIMS: Tissue inhibitors of metalloproteinase (TIMPs) bind to active matrix
      metalloproteinase (MMPs), and thereby inhibit their proteolytic activity. We
      investigated the role of polymorphisms in the gene for TIMP-1 and serum levels of
      TIMP-1 in association with postmyocardial infarction (MI), left ventricular (LV)
      dysfunction, and symptoms of acute heart failure (AHF) in patients treated with
      primary percutaneous coronary intervention. METHODS: In total, 556 patients with
      STEMI were evaluated. Levels of TIMP-1 were measured at admission and 24 h after
      MI onset. The TIMP-1 exon 5 SNP rs4898 (F124F with T>C) located at X chromosome
      was assayed. RESULTS: TIMP-1 levels were higher for men with AHF as well as for
      men with LV dysfunction (ejection fraction [EF]<40%). According to multivariate
      analysis, the TIMP-1 level was a factor with an independent negative relationship
      to EF and AHF in men. An independent relationship between exon 5 TIMP-1 gene
      polymorphism and EF, AHF or TIMP-1 level was not documented. CONCLUSION: These
      results provide evidence that a higher level of circulating TIMP-1 is
      independently associated with worse EF and AHF.

PMID- 22971140
TI  - Distribution of the IL-1RN, IL-6, IL-10, INF-gamma, and TNF-alpha Gene
      Polymorphisms in the Mexican Population.
AB  - BACKGROUND: Cytokines are a group of polypeptides with an important role in the
      inflammatory response. It has been suggested that certain polymorphisms located
      in several cytokine genes are associated with different diseases. The aim of the
      present study was to establish the gene frequency of 13 polymorphisms of the IL
      1RN, IL-6, IL-10, INF-gamma, and TNF-alpha genes in a Mexican population. These
      polymorphisms have been reported in several populations, with important variation
      in frequency according to the studied population. METHODS: Thirteen polymorphisms
      (rs419598, rs315951, rs2234663, rs3811058, rs1800796, rs2069827, rs1800896,
      rs1800871, rs1800872, rs1800629, rs2069709, rs2069710, and rs361525) were
      analyzed by 5' exonuclease TaqMan genotyping assays in a group of 248 healthy
      unrelated Mexican individuals. RESULTS: The results obtained showed that the
      studied Mexican population presents significant differences (p<0.05) in the
      distribution of the IL1RN (rs419598, rs315951, and and rs2234663), IL1F10
      (rs3811058), IL6 (rs1800796, rs2069827), IL10 (rs1800896, rs1800871, and
      rs1800872), and TNF-alpha (rs1800629) polymorphisms when compared to Caucasian,
      Asian, and African populations. CONCLUSIONS: In summary, the distribution of the
      IL-1RN, IL-6, IL-10, and TNF-alpha cytokine gene polymorphisms distinguishes the
      studied Mexican population from other groups. Since the alleles of these
      cytokines are associated with the development of several inflammatory diseases,
      knowledge of the distribution of these alleles in the studied Mexican population
      could be helpful to understand their true role as a genetic susceptibility marker
      in this population.

PMID- 22971141
TI  - Alpha-1-antitrypsin deficiency in Serbian adults with lung diseases.
AB  - AIM: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and
      severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early
      onset emphysema. Despite the relatively high prevalence of A1ATD, this condition
      is frequently underdiagnosed. Our aim was to determine the distribution of the
      A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian
      population. METHODS: The study included the adults with chronic obstructive
      pulmonary disease (COPD) (n=348), asthma (n=71), and bronchiectasis (n=35); the
      control was 1435 healthy blood donors. The A1ATD variants were identified by
      isoelectric focusing or polymerase chain reaction-mediated site-directed
      mutagenesis. RESULTS: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers
      are associated with significantly higher risk of developing COPD than healthy
      individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated
      prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8,
      and 1:1243) than in the Serbian population (1:5519, 1:38, and 1:5519).
      CONCLUSION: The high prevalence of A1ATD phenotypes/allele in our population has
      confirmed the necessity of screening for A1ATD in patients with COPD. On the
      other hand, on the basis of the estimated number of those with A1ATD among the
      COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the
      Serbian population.

PMID- 22971142
TI  - Common genetic variants of the BMP4, BMPR1A, BMPR1B, and ACVR1 genes, left
      ventricular mass, and other parameters of the heart in newborns.
AB  - The members of the family of bone morphogenetic proteins (BMPs) are important
      regulators in cardiac development. The present study was designed to evaluate the
      effect of common genetic variants of BMP-4 and its receptors BMPR1A, BMPR1B, and
      ACVR1 on left ventricular mass (LVM) and other parameters of the heart and blood
      pressure in newborns. The study included 210 healthy newborns. Two-dimensional M
      mode echocardiography was used to assess LVM between days 3 and 4 after birth.
      Polymorphisms were determined by the polymerase chain reaction-restriction
      fragment length polymorphism technique. We found lack of associations between
      LVM, values of blood pressure, and the BMP4, BMPR1A, BMPR1B, and ACVR1 genotypes.
      A significant association was observed between the 455C allele of BMP4 and
      increased left ventricular internal diameter systolic (p=0.004) and between 1650T
      allele of BMPR1B and lower left atrium diameter (p=0.038). Presence of the 455C
      allele of BMP4 and the 8474T allele of ACVR1 gene was significantly associated
      with decreased left ventricular ejection fraction (LVEF) (p=0.0004 and p=0.046,
      respectively). The 455C allele of BMP4 and the 8474T allele of ACVR1 may play a
      role as significant predictors for decreased LVEF in newborns.

PMID- 22971143
TI  - Neuromapping techniques in drug discovery: pharmacological MRI for the assessment
      of novel antipsychotics.
AB  - INTRODUCTION: Treatment of psychiatric and neurological diseases represents a
      substantial unmet medical need, but the development of novel, effective and safe
      drugs is proving difficult. While substantial improvement over existing
      pharmacological agents is expected from new molecular targets emerging in the
      genomic era, the validation and exploitation of novel mechanisms of action is a
      lengthy and costly process. The use of neuroimaging techniques, and more
      specifically of functional and pharmacological magnetic resonance imaging (MRI),
      has been advocated as a powerful approach to this problem, providing
      translational biomarkers for the objective assessment of drug activity on brain
      function, and possibly surrogate markers of clinical response. AREAS COVERED: The
      authors review the recent application of functional and pharmacological MRI
      (phMRI) in the study of novel treatments of psychosis based on glutamatergic
      mechanisms. Furthermore, they review contribution of functional imaging in the
      target validation and early assessment of drugs exploiting glutamatergic
      mechanisms as an example of potentially impactful exploitation of neuroimaging
      methods in drug discovery. EXPERT OPINION: While functional neuroimaging methods
      may provide useful markers of drug activity and response to treatment, their
      translational potential, that is, their use to bridge animal and human
      investigations is seldom exploited. The application of phMRI in the study of
      novel antipsychotics based on glutamatergic mechanisms represents an example of
      functional neuroimaging as a powerful means to link preclinical and clinical
      research, thus providing a paradigm that may help expedite progression into the
      clinical phase of novel mechanisms for the treatment of psychiatric and
      neurological diseases.

PMID- 22971144
TI  - Morphometric changes in the dog trochlear nerve with growth.
AB  - The objective of this work was to analyse changes in morphometric characteristics
      related to growth in the trochlear nerve in dogs. Twenty beagles, split into four
      dog age groups (A, 7 days; B, 21 days; C, 35 days; D, 49 days and E, 4 years),
      were used. The right intracranial portion of the nerve was analysed by light and
      electron microscopy. The nerve cross-sectional area was calculated. Number,
      diameter and cross-sectional area of unmyelinated and myelinated fibres were also
      calculated. In myelinated fibres, the corresponding axon area and diameter and
      myelin sheath thickness were also calculated. The number of myelinated and
      unmyelinated fibres was 1070.25+/-112.07 and 592.25+/-467.53 in group A, 1367+/
      57.98 and 143.67+/-54.37 in group B, 1574.20+/-299.50 and 151.67+/-51.73 in group
      C, 1340.33+/-151 and 127+/-48.75 in group D and 1476+/-260.71 and 284+/-101.82 in
      group E. The mean diameter for myelinated and unmyelinated fibres was 4.37+/-0.17
      MUm and 0.41+/-0.08 MUm for group A; 6.21+/-0.12 MUm and 0.30+/-0.03 MUm for B;
      6.90+/-0.91 MUm and 0.32+/-0.03 MUm for C; 7.86+/-1.19 MUm and 0.32+/-0.02 MUm
      for D; 10.63+/-0.50 MUm and 0.30+/-0.01 MUm for E, respectively. This nerve
      possesses similar structural and ultrastructural features to the same nerve in
      other species and modifies its morphometry with growth. Results could enhance the
      understanding of pathological disorders.

PMID- 22971145
TI  - Editorial comment to postoperative phosphodiesterase type 5 inhibitor
      administration increases the rate of urinary continence recovery after bilateral
      nerve-sparing radical prostatectomy.

PMID- 22971146
TI  - Aptamer-based impedimetric sensor for bacterial typing.
AB  - The development of an aptamer-based impedimetric sensor for typing of bacteria
      (AIST-B) is presented. Highly specific DNA aptamers to Salmonella enteritidis
      were selected via Cell-SELEX technique. Twelve rounds of selection were
      performed; each comprises a positive selection step against S. enteritidis and a
      negative selection step against a mixture of related pathogens, including
      Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Pseudomonas
      aeruginosa, and Citrobacter freundii, to ensure the species-specificity of the
      selected aptamers. After sequencing of the pool showing the highest binding
      affinity to S. enteritidis, a DNA sequence of high affinity to the bacteria was
      integrated into an impedimetric sensor via self-assembly onto a gold
      nanoparticles-modified screen-printed carbon electrode (GNPs-SPCE). Remarkably,
      this aptasensor is highly selective and can successfully detect S. enteritidis
      down to 600 CFU mL(-1) (equivalent to 18 CFU in 30 MUL assay volume) in 10 min
      and distinguish it from other Salmonella species, including S. typhimurium and S.
      choleraesuis. This report is envisaged to open a new venue for the aptamer-based
      typing of a variety of microorganisms using a rapid, economic, and label-free
      electrochemical platform.

PMID- 22971147
TI  - Direct growth of doping-density-controlled hexagonal graphene on SiO2 substrate
      by rapid-heating plasma CVD.
AB  - A transfer-free method for growing carrier-density-controlled graphene directly
      on a SiO(2) substrate has been realized for the first time by rapid-heating
      plasma chemical vapor deposition (RH-PCVD). Using this method, high-quality
      single-layer graphene sheets with a hexagonal domain can be selectively grown
      between a Ni film and a SiO(2) substrate. Systematic investigations reveal that
      the relatively thin Ni layer, rapid heating, and plasma CVD are critical to the
      success of this unique method of graphene growth. By applying this technique, an
      easy and scalable graphene-based field effect transistor (FET) fabrication is
      also demonstrated. The electrical transport type of the graphene-based FET can be
      precisely tuned by adjusting the NH(3) gas concentration during the RH-PCVD
      process.

PMID- 22971148
TI  - A descriptive study of the "lift-assist" call.
AB  - INTRODUCTION: Responses for "lift assists" (LAs) are common in many emergency
      medical services (EMS) systems, and result when a person dials 9-1-1 because of
      an inability to get up, is subsequently determined to be uninjured, and is not
      transported for further medical attention. Although LAs often involve recurrent
      calls and are generally not reimbursable, little is known of their operational
      effects on EMS systems. We hypothesized that LAs present an opportunity for
      earlier treatment of subtle-onset medical conditions and injury prevention
      interventions in a population at high risk for falls. Objectives. To quantify LA
      calls in one community, describe EMS returns to the same address within 30 days
      following an index LA call, and characterize utilization of EMS by LA patients.
      METHODS: Data from the computer-aided dispatch (CAD) system of a suburban fire
      based EMS system were retrospectively reviewed. All LAs from 2004 to 2009 were
      identified using "exit codes" transmitted by paramedics after each call. The
      number and nature of return visits to the same address within 30 days were
      examined. RESULTS: From 2004 through 2009, there were 1,087 LA responses (4.8% of
      EMS incidents) to 535 different addresses. Two-thirds of the LA calls (726;
      66.8%) were to one-third of these addresses (174 addresses; 32.5%); 563 of the
      return calls to the same address occurred within 30 days after the index LA. For
      214 of these return visits, it was possible to compare patient age and sex with
      those associated with the initial LA, revealing that 85% of return visits were
      likely for the same patients. Of these, 38.5% were for another LA/refusal of
      transport, 8.2% for falls and other injuries, and 47.3% for medical complaints.
      Hospital transport was required in 55.5% of these return visits. The EMS crews
      averaged 21.5 minutes out of service per LA call. CONCLUSION: Lift-assist calls
      are associated with substantial subsequent utilization of EMS, and should trigger
      fall prevention and other safety interventions. Based on our data, these calls
      may be early indicators of medical problems that require more aggressive
      evaluation.

PMID- 22971149
TI  - Characterizing the fatty acid binding site in the cavity of potassium channel
      KcsA.
AB  - We show that interactions of fatty acids with the central cavity of potassium
      channel KcsA can be characterized using the fluorescence probe 11
      dansylaminoundecanoic acid (Dauda). The fluorescence emission spectrum of Dauda
      bound to KcsA in bilayers of dioleoylphosphatidylcholine contains three
      components, which can be attributed to KcsA-bound and lipid-bound Dauda together
      with unbound Dauda. The binding of Dauda to KcsA was characterized by a
      dissociation constant of 0.47 +/- 0.10 MUM with 0.94 +/- 0.06 binding site per
      KcsA tetramer. Displacement of KcsA-bound Dauda by the tetrabutylammonium (TBA)
      ion confirmed that the Dauda binding site was in the central cavity of KcsA.
      Dissociation constants for a range of fatty acids were determined by displacement
      of Dauda: binding of fatty acids increased in strength with an increasing chain
      length from C14 to C20 but then decreased in strength from C20 to C22. Increasing
      the number of double bonds in the chain from one to four had little effect on
      binding, dissociation constants for oleic acid and arachidonic acid, for example,
      being 2.9 +/- 0.2 and 3.0 +/- 0.4 MUM, respectively. Binding of TBA to KcsA was
      very slow, whereas binding of Dauda was fast, suggesting that TBA can enter the
      cavity only through an open channel whereas Dauda can bind to the closed channel,
      presumably entering the cavity via the lipid bilayer.

PMID- 22971150
TI  - Quality of work life among primary health care nurses in the Jazan region, Saudi
      Arabia: a cross-sectional study.
AB  - BACKGROUND: Quality of work life (QWL) is defined as the extent to which an
      employee is satisfied with personal and working needs through participating in
      the workplace while achieving the goals of the organization. QWL has been found
      to influence the commitment and productivity of employees in health care
      organizations, as well as in other industries. However, reliable information on
      the QWL of primary health care (PHC) nurses is limited. The purpose of this study
      was to assess the QWL among PHC nurses in the Jazan region, Saudi Arabia.
      METHODS: A descriptive research design, namely a cross-sectional survey, was used
      in this study. Data were collected using Brooks' survey of quality of nursing
      work life and demographic questions. A convenience sample was recruited from 134
      PHC centres in Jazan, Saudi Arabia. The Jazan region is located in the southern
      part of Saudi Arabia. A response rate of 91% (n = 532/585) was achieved
      (effective response rate = 87%, n = 508). Data analysis consisted of descriptive
      statistics, t-test and one way-analysis of variance. Total scores and subscores
      for QWL items and item summary statistics were computed and reported using SPSS
      version 17 for Windows. RESULTS: Findings suggested that the respondents were
      dissatisfied with their work life. The major influencing factors were unsuitable
      working hours, lack of facilities for nurses, inability to balance work with
      family needs, inadequacy of vacations time for nurses and their families, poor
      staffing, management and supervision practices, lack of professional development
      opportunities, and an inappropriate working environment in terms of the level of
      security, patient care supplies and equipment, and recreation facilities (break
      area). Other essential factors include the community's view of nursing and an
      inadequate salary. More positively, the majority of nurses were satisfied with
      their co-workers, satisfied to be nurses and had a sense of belonging in their
      workplaces. Significant differences were found according to gender, age, marital
      status, dependent children, dependent adults, nationality, nursing tenure,
      organizational tenure, positional tenure, and payment per month. No significant
      differences were found according to education level of PHC nurses and location of
      PHC. CONCLUSIONS: These findings can be used by PHC managers and policy makers
      for developing and appropriately implementing successful plans to improve the
      QWL. This will help to enhance the home and work environments, improve individual
      and organization performance and increase the commitment of nurses.

PMID- 22971151
TI  - Pitavastatin ameliorated the progression of steatohepatitis in ovariectomized
      mice fed a high fat and high cholesterol diet.
AB  - AIM: Many studies indicate an accelerated progression of non-alcoholic
      steatohepatitis (NASH) in postmenopausal women. Very recently, we reported that
      estrogen deficiency enhanced the progression of steatohepatitis in mice fed a
      high fat and high cholesterol (HFHC) diet. Hypercholesterolemia is often observed
      in postmenopausal women, and recent studies indicate it to be an important risk
      factor for the progression of NASH. Statins can slow NASH progression in the
      estrogen-deficient state but the precise mechanisms of their effects are still
      unclear. METHODS: We investigated the effects of pitavastatin on steatohepatitis
      progression using ovariectomized (OVX) mice fed a HFHC diet or HFHC + pitava diet
      (containing 5 p.p.m. pitavastatin) for 6 weeks. RESULTS: Serum alanine
      aminotransferase and cholesterol levels significantly decreased in mice fed the
      HFHC + pitava diet compared with mice fed the HFHC diet. Real-time reverse
      transcription polymerase chain reaction representing hepatic inflammatory gene
      expressions significantly decreased in mice fed the HFHC + pitava diet compared
      with the HFHC-fed mice. Pitavastatin treatment also decreased both hepatic
      macrophage infiltration and hepatocyte chemokine (C-C motif) ligand 2 expression
      and improved the liver fibrosis condition when compared with the mice fed the
      HFHC diet. In addition, the enhanced spleen monocyte chemokine (C-C motif)
      receptor 2 expression in ovariectomized mice fed the HFHC diet was also decreased
      by pitavastatin administration. CONCLUSION: Our study demonstrated that the
      exacerbated steatohepatitis progression in OVX mice fed a HFHC diet could be
      attenuated by pitavastatin treatment at least through inhibition of hepatic
      macrophage infiltration. We concluded that statins should be useful for treating
      NASH in postmenopausal women.

PMID- 22971152
TI  - Suicide prevention for youth--a mental health awareness program: lessons learned
      from the Saving and Empowering Young Lives in Europe (SEYLE) intervention study.
AB  - BACKGROUND: The Awareness program was designed as a part of the EU-funded Saving
      and Empowering Young Lives in Europe (SEYLE) intervention study to promote mental
      health of adolescents in 11 European countries by helping them to develop problem
      solving skills and encouraging them to self-recognize the need for help as well
      as how to help peers in need. METHODS: For this descriptive study all
      coordinators of the SEYLE Awareness program answered an open-ended evaluation
      questionnaire at the end of the project implementation. Their answers were
      synthesized and analyzed and are presented here. RESULTS: The results show that
      the program cultivated peer understanding and support. Adolescents not only
      learned about mental health by participating in the Awareness program, but the
      majority of them also greatly enjoyed the experience. CONCLUSIONS:
      Recommendations for enhancing the successes of mental health awareness programs
      are presented. Help and cooperation from schools, teachers, local politicians and
      other stakeholders will lead to more efficacious future programs.

PMID- 22971153
TI  - Identification of human remains by DNA analysis of the gastrointestinal contents
      of fly larvae.
AB  - Dipterous fly larvae (maggots) are frequently collected from a corpse during a
      criminal investigation. Previous studies showed that DNA analysis of the
      gastrointestinal contents of maggots might be used to reveal the identity of a
      victim. However, this approach has not been used to date in legal investigations,
      and thus its practical usefulness is unknown. A badly burned body was discovered
      with its face and neck colonized by fly larvae. Given the condition of the body,
      identification was not possible. Short tandem repeat (STR) typing was performed
      using the gastrointestinal contents of maggots collected from the victim and was
      compared to STR profiles obtained from the alleged father. The probability of
      paternity was 99.685%. Thus, this comparative DNA test enabled the conclusive
      identification of the remains. This is the first reported case of analysis of
      human DNA isolated from the gastrointestinal tract of maggots used to identify a
      victim in a criminal case.

PMID- 22971154
TI  - The cost-effectiveness of ESBL detection: towards molecular detection methods?
AB  - Correct detection of extended-spectrum beta-lactamases (ESBLs) is crucial for
      infection control and antibiotic choice. We performed a study to determine the
      cost-effectiveness of phenotypical testing, which can be inaccurate, and
      genotypical tests, which are considered to be more reliable but also more
      expensive. All patients that had been in isolation in the Amphia hospital because
      of the detection of ESBL according to the ESBL Etest were included in the survey.
      All strains were retested using the double disk confirmation test (DDCT) and a
      genotypical method. This was a commercially available microarray (Check-Points).
      Discordant results were confirmed by PCR and sequencing. In total 174 patients
      were included. In 24 of 174 (14%) patients, ESBL carriage could not be confirmed
      with the microarray. This was verified with PCR and sequencing. The mean duration
      of isolation was 15 days, adding up to a total number of isolation days of 2571.
      False-positive results according to the microarray resulted in a total of 279
      days of unnecessary isolation for the Etest and 151 days for the DDCT. Using
      Etest to detect the presence of ESBL results in a false-positive outcome in 14%
      of the cases. This results in unnecessary isolation of patients, which can be
      omitted by using a genotypic method.

PMID- 22971156
TI  - Selective JAK1 inhibitor and selective Tyk2 inhibitor patents.
AB  - INTRODUCTION: The JAK family comprises of the four non-receptor tyrosine kinases
      JAK1, JAK2, JAK3 and Tyk2, which play key, but differing, roles in cytokine
      receptor signal transduction. A non-selective JAK inhibitor, ruxolitinib, has
      recently been approved to treat myelofibrosis whereas tofacitinib is poised for
      approval to treat rheumatoid arthritis. Selective inhibition of JAK3, JAK1 or
      Tyk2 provides the opportunity to achieve clinical efficacy in the treatment of
      inflammatory diseases while reducing the risk of dose-limiting effects
      attributable to JAK2 inhibition. AREAS COVERED: This review considers the small
      number of published patent filings that claim either selective JAK1 or selective
      Tyk2 inhibitors. These are considered in the context of the considerably larger
      number of disclosures and patent filings claiming selective JAK2 or JAK3
      inhibitors. EXPERT OPINION: The recent disclosure of the clinical efficacy of a
      selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed
      disclosure of the some potent and highly selective JAK1 inhibitors provide a
      clear stimulus for further activity in this area. The availability of a selective
      Tyk2 inhibitor will provide the opportunity for better understanding of the
      physiological role of this kinase. Recent patent applications indicate that Tyk2
      selectivity is achievable and Tyk2 inhibitors have potential in the treatment of
      multiple sclerosis.

PMID- 22971157
TI  - Standard operational procedures for low sexual desire in men.
AB  - INTRODUCTION: Low sexual desire in men is a condition that has received little
      attention; nevertheless it occurs with high frequency. Clinicians are in need of
      clear guidelines to address this problem. AIM: To develop standardized
      operational procedures to be implemented with men presenting low sexual
      desire/interest (LSD/I). METHODS: Review of relevant evidence-based literature
      and published guidelines, integrated with expert opinion. MAIN OUTCOME:
      Operational procedures for LSD/I that are recommended for clinical practice with
      various degrees of support from published evidence. RESULTS: A new classification
      scheme is proposed; LSD/I is proposed as an umbrella term for which hypoactive
      sexual desire disorder (HSDD) is only a subtype. The following standard
      operational procedures are described: (i) Detection of LSD/I: screening for
      LSD/I, screening for LSD/I in patients with other sexual dysfunctions; (ii)
      Diagnosis and assessment of etiology: diagnostic criteria for LSD/I, assessment
      of depression status, assessment of relationship status, assessment of
      endocrinologic status, diagnostic criteria for HSDD in men; (iii) TREATMENT:
      treatment of LSD/I secondary to low testosterone, treatment of LSD/I secondary to
      elevated prolactin, treatment of LSD/I secondary to other endocrinologic
      disorders, treatment of LSD/I secondary to depressive illness and or anxiety
      disorders, treatment of LSD/I secondary to relationship conflict and treatment of
      HSDD. A diagnostic and treatment algorithm is presented. CONCLUSIONS: LSD/I is a
      common condition that should be identified in patients; it is recommended that
      this condition be actively investigated by the clinician. Once the diagnosis of
      LSD/I in men is confirmed, a thorough search for possible causes needs to include
      both biological and psychological causes. TREATMENT should be etiologically
      oriented.

PMID- 22971158
TI  - Acute toxicity due to the confirmed consumption of synthetic cannabinoids:
      clinical and laboratory findings.
AB  - AIMS: Recently, several synthetic cannabinoids were identified in herbal mixtures
      consumed as recreational drugs alternative to cannabis products. The aim was to
      characterize the acute toxicity of synthetic cannabinoids as experienced by
      emergency patients. DESIGN: This was a retrospective study targeting patients
      seeking emergency treatment after recreational use of synthetic cannabinoids.
      SETTING AND PARTICIPANTS: Patients were selected from the database of the Poisons
      Information Center Freiburg between September 2008 and February 2011. The
      inclusion criteria were: hospitalization, available clinical reports and
      analytical verification of synthetic cannabinoid uptake. In total, 29 patients
      were included (age 14-30 years, median 19; 25 males, four females). MEASUREMENTS:
      Clinical reports were evaluated and synthetic cannabinoids and other drugs were
      determined analytically. FINDINGS: CP-47,497-C8 (one), JWH-015 (one), JWH-018
      (eight), JWH-073 (one), JWH-081 (seven), JWH-122 (11), JWH-210 (11), JWH-250
      (four) and AM 694 (one) were quantified in blood samples. JWH-018 was most common
      in 2008-9, JWH-122 in 2010, and JWH-210 in 2011. Tachycardia, agitation,
      hallucination, hypertension, minor elevation of blood glucose, hypokalaemia and
      vomiting were reported most frequently. Chest pain, seizures, myoclonia and acute
      psychosis were also noted. CONCLUSIONS: There appears to have been an increase in
      use of the extremely potent synthetic cannabinoids JWH-122 and JWH-210. Acute
      toxic symptoms associated with their use are also reported after intake of high
      doses of cannabis, but agitation, seizures, hypertension, emesis and hypokalaemia
      seem to be characteristic to the synthetic cannabinoids, which are high-affinity
      and high-efficacy agonists of the CB(1)  receptor. Thus, these effects are due
      probably to a strong CB(1)  receptor stimulation.

PMID- 22971159
TI  - Analysis of cytochrome P450 gene polymorphism in a lupus nephritis patient in
      whom tacrolimus blood concentration was markedly elevated after administration of
      azole antifungal agents.
AB  - WHAT IS KNOWN AND OBJECTIVE: Both itraconazole (ITCZ) and voriconazole (VCZ) are
      potent inhibitors of cytochrome P450 (CYP) 3A, and their effects have been
      reported to be equal. However, ITCZ is metabolized by CYP3A, whereas VCZ is
      mainly metabolized by CYP2C9 and CYP2C19 and only partially by CYP3A. We
      experienced the case of a patient who showed a 5-fold increase in trough levels
      of tacrolimus (FK) level after switching from ITCZ to VCZ. Our objective is to
      discuss the mechanism of the increase drug-drug interaction in terms of serum
      concentration of the azole drugs and patient pharmacogenomics. CASE SUMMARY: A 53
      year-old woman was treated with FK (1 mg/day) for lupus nephritis. Because fungal
      infection was suspected, she received ITCZ (100 mg/day). When ITCZ was replaced
      with VCZ (400 mg/day), the blood concentration of FK increased markedly from 6.1
      to 34.2 ng/mL. During coadministration with FK, the levels of ITCZ and VCZ were
      135.5 ng/mL and 5.5 MUg/mL, respectively, with the VCZ level around 3-fold higher
      than the previously reported level (1.4-1.8 MUg/mL). Her CYP genotypes were
      CYP2C19*1/*2, CYP3A4*1/*1 and CYP3A5*3/*3. WHAT IS NEW AND CONCLUSION: The
      patient was a CYP2C19 intermediate metabolizer (IM) and deficient in CYP3A5. The
      increase in plasma VCZ level appears to have been at least in part, associated
      with the CYP2C19 IM phenotype. One possible explanation for the marked increase
      in blood FK concentration was increased inhibition of CYP3A because of the
      impaired metabolism and subsequent increased plasma concentration of VCZ. This
      case shows that the severity of drug interactions may be influenced by metabolic
      gene polymorphism.

PMID- 22971161
TI  - Healthcare professional and patient perceptions of a new prefilled insulin pen
      versus vial and syringe.
AB  - OBJECTIVE: Usability of a new prefilled insulin pen, FlexTouch(r) (FT; Novo
      Nordisk A/S, Bagsvaerd, Denmark), with no push-button extension and low injection
      force, was compared with vial and syringe (V&S). RESEARCH DESIGN AND METHODS:
      People with diabetes, and healthcare professionals with diabetes management
      experience conducted test injections and answered questions on preference, ease
      of use, confidence, ease of learning and teaching. RESULTS: The study involved 30
      needle-naive patients (naive to any diabetes injection therapy), 30 V&S
      experienced patients, 30 physicians and 30 nurses. In the total population, FT
      was preferred to V&S for teaching or learning to use (both p < 0.001). Nurses
      (100 vs. 0%) and physicians (87 vs. 7%) preferred FT to V&S for ease of teaching.
      V&S-experienced (73 vs. 7%) and needle-naive patients (83 vs. 7%) preferred FT to
      V&S for ease of learning. The remainder chose "equally easy/difficult." More
      participants in each group rated FT "very/fairly easy" for ease of depressing the
      push-button/plunger (FT vs. V&S: physicians, 93 vs. 80%; nurses, 97 vs. 80%; V&S
      experienced patients, 93 vs. 90%; needle-naive patients, 100 vs. 77%), and
      injecting three doses. More participants were "very/rather confident" in managing
      daily injections using FT (FT vs. V&S: physicians, 100 vs. 60%; nurses, 100 vs.
      70%; V&S-experienced patients, 93 vs. 90%; needle-naive patients, 90 vs. 40%).
      CONCLUSIONS: FT was rated easier to use, learn to use or teach to use than V&S by
      patients with or without experience of insulin injection with V&S, and by
      physicians and nurses with diabetes management experience.

PMID- 22971162
TI  - Insulin receptor and glucose transporters mRNA expression throughout the
      menstrual cycle in human endometrium: a physiological and cyclical condition of
      tissue insulin resistance.
AB  - The expression of insulin receptor (IR), together with that of glucose
      transporters 1 and 4 (GLUT1-4) and of Insulin Growth Factor-I and -II (IGF-I,-II)
      in the endometrium of healthy and young women in both phases of menstrual cycle
      was assessed. Sixteen out of 20 healthy and normal menstruating volunteers were
      studied. Endometrial samplings were performed in every subject, twice in the same
      cycle, during the follicular and luteal phase respectively. The mRNA expression
      of IR, GLUT1-4, IGF-I and -II were evaluated by real-time quantitative RT-PCR and
      immunostaining reactions. Our results indicate that IR, GLUT1-4, IGF-I and -II
      mRNAs were expressed in both phases of the endometrial cycle: GLUT4 and IGF-I
      mRNA expression were significantly higher in the follicular phase and localized
      at the epithelial and stromal cell level, respectively, whereas IR, GLUT1 and IGF
      II mRNA expression were mostly present in the secretory phase and mainly
      localized at the stromal level. An inverse tendency of IR and GLUT4 mRNA
      expression was respectively observed from follicular to luteal phase. In
      conclusion our data suggest that IR, glucose transporters and IGFs are
      significantly and differently expressed at the endometrial level throughout the
      menstrual cycle and that human endometrium cyclically undergoes through a
      transitory condition from normal to an insulin-resistance state.

PMID- 22971160
TI  - Molecular circumscription and major evolutionary lineages of the fern genus
      Dryopteris (Dryopteridaceae).
AB  - BACKGROUND: The fern genus Dryopteris (Dryopteridaceae) is among the most common
      and species rich fern genera in temperate forests in the northern hemisphere
      containing 225-300 species worldwide. The circumscription of Dryopteris has been
      controversial and various related genera have, over the time, been included in
      and excluded from Dryopteris. The infrageneric phylogeny has largely remained
      unclear, and the placement of the majority of the supraspecific taxa of
      Dryopteris has never been tested using molecular data. RESULTS: In this study,
      DNA sequences of four plastid loci (rbcL gene, rps4-trnS spacer, trnL intron,
      trnL-F spacer) were used to reconstruct the phylogeny of Dryopteris. A total of
      122 accessions are sampled in our analysis and they represent 100 species of the
      expanded Dryopteris including Acrophorus, Acrorumohra, Diacalpe, Dryopsis,
      Nothoperanema, and Peranema. All four subgenera and 19 sections currently
      recognized in Dryopteris s.s. are included. One species each of Arachniodes,
      Leptorumohra, and Lithostegia of Dryopteridaceae are used as outgroups. Our study
      confirms the paraphyly of Dryopteris and provides the first strong molecular
      evidence on the monophyly of Acrophorus, Diacalpe, Dryopsis, Nothoperanema, and
      Peranema. However, all these monophyletic groups together with the paraphyletic
      Acrorumohra are suggested to be merged into Dryopteris based on both molecular
      and morphological evidence. Our analysis identified 13 well-supported
      monophyletic groups. Each of the 13 clades is additionally supported by
      morphological synapomophies and is inferred to represent a major evolutionary
      lineage in Dryopteris. In contrast, monophyly of the four subgenera and 15 out of
      19 sections currently recognized in Dryopteris s.s is not supported by plastid
      data. CONCLUSIONS: The genera, Acrophorus, Acrorumohra, Diacalpe, Dryopsis,
      Nothoperanema, and Peranema, should all be merged into Dryopteris. Most species
      of these genera share a short rhizome and catadromic arrangement of frond
      segments, unlike the sister genus of Dryopteris s.l., Arachniodes, which has
      anadromic arrangement of frond segments. The non-monophyly of the 19 out of the
      21 supraspecific taxa (sections, subgenera) in Dryopteris strongly suggests that
      the current taxonomy of this genus is in need of revision. The disagreement
      between the previous taxonomy and molecular results in Dryopteris may be due
      partly to interspecific hybridization and polyplodization. More morphological
      studies and molecular data, especially from the nuclear genome, are needed to
      thoroughly elucidate the evolutionary history of Dryopteris. The 13 well
      supported clades identified based on our data represent 13 major evolutionary
      lineages in Dryopteris that are also supported by morphological synapomophies.

PMID- 22971163
TI  - The outcomes of mycophenolate mofetil therapy combined with systemic
      corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To study the effectiveness of mycophenolate mofetil (MMF) as first-line
      therapy combined with systemic corticosteroids in acute uveitis associated with
      Vogt-Koyanagi-Harada (VKH) disease. The outcomes in this group were compared with
      those of another group of patients with VKH disease who were treated with
      corticosteroid monotherapy or with delayed addition of immunomodulatory therapy.
      METHODS: This prospective study included 19 patients (38 eyes) diagnosed with
      acute uveitis associated with VKH disease. RESULTS: The mean follow-up period was
      27.0 +/- 11.1 months (range 16-54 months). Corticosteroid-sparing effect was
      achieved in all patients. The mean interval between starting treatment and
      tapering prednisone to 10 mg or less daily was 5.1 +/- 1.2 months (range 3-7
      months). Ten (53%) patients discontinued treatment without relapse of
      inflammation. The mean time observed of treatment was 17.3 +/- 11.9 months (range
      3-41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the
      corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001).
      Recurrent inflammation of >=3 times was reduced significantly (p = 0.0383) in the
      corticosteroid + MMF group (3%) as compared to corticosteroid group (18%).
      Development of all complications was significantly higher in the corticosteroid
      group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None
      of the eyes in the corticosteroid + MMF group developed 'sunset glow fundus'.
      CONCLUSIONS: Addition of MMF as first-line therapy to corticosteroids in patients
      with acute uveitis associated with VKH disease leads to significant reduction in
      recurrences of uveitis and development of late complications and significantly
      improves visual outcome.

PMID- 22971164
TI  - Outcomes of patients with multiple myeloma and renal impairment treated with
      bortezomib, cyclophosphamide, and dexamethasone without plasma exchange.

PMID- 22971165
TI  - Modelling salmon lice, Lepeophtheirus salmonis, reproduction on farmed Atlantic
      salmon, Salmo salar L.
AB  - The aim of this study was to model sea lice levels and the effect on reproduction
      by a stochastic simulation model and to evaluate the uncertainty of lice
      estimates based upon counts. Two empirical data sets were examined to
      parameterize the models. An overall fit of the data to the Poisson distribution
      was found and thus was used as the base of the stochastic models. In the model,
      salmon lice reproduction is not linear with the number of adult females and at
      low lice loads a smaller proportion of the adult female lice will reproduce.
      Depending on the variance structure, it was estimated that between 40% and 60% of
      the adult female lice will reproduce at an abundance of 0.5 adult females per
      fish. Lice counts, especially when examining few fish at low lice loads, are
      uncertain and at a true abundance of 0.1 one may count between 0 and 5 lice when
      examining 10 fish. Understanding the dynamics of sea lice reproduction is a key
      factor in the development of sustainable control strategies.

PMID- 22971166
TI  - A chick embryo with a yet unclassified type of cephalothoracopagus malformation
      and a hypothesis for explaining its genesis.
AB  - Cephalothoracopagus embryos are conjoined twins, who share parts of their heads,
      necks and bodies. Our study aims at presenting a detailed morphological analysis
      of a cephalothoracopagus chick embryo of developmental stage 31. Because none of
      the existing theories can explain the genesis of the phenotype of this embryo, we
      also suggest a hypothesis, which explains it. Beside the cephalothoracopagus
      embryo, we investigated five control embryos. With the aid of the high-resolution
      episcopic microscopy (HREM) technique, we created digital volume data and three
      dimensional (3D) computer models of the organs and arteries of the embryos. We
      used the 3D models for topological analysis and for measuring the diameters of
      the great intrathoracic arteries. The malformed embryo showed two body backs,
      each containing a notochord, spinal cord and dorsal aorta. The body backs
      continued into separated lower bodies. The embryo had a single, four-chambered
      heart, single respiratory tract and single upper alimentary tract. The topology
      of the pharyngeal arch arteries was normal, and the diameters of these arteries
      were similar to that of the control embryos. We classified the embryo we
      investigated as a yet unknown malformation and suggest a hypothesis explaining
      its genesis.

PMID- 22971167
TI  - Capillary electrophoresis mass spectrometry for the characterization of O
      acetylated N-glycans from fish serum.
AB  - O-acetylated N-glycans from fish serum of Atlantic salmon (Salmo salar) are
      characterized by capillary electrophoresis (CE) in conjunction with both laser
      induced fluorescence (LIF) and mass spectrometry (MS) detection methods. Glycans
      derivatized with negatively charged fluorescent label 8-aminopyrene-1,2,6
      trisulfonate (APTS) were separated to obtain a CE-LIF profile of the complex
      glycan mixture, and the profile concurs with that obtained by using electrospray
      mass spectrometry. The identity of the APTS-labeled glycans was confirmed by CE
      MS. The same glycans can be identified also in their native state by CE-MS
      without derivatization. The structural variations of O-acetylated sialic acid
      isomers in fish serum glycans are investigated by CE-MS/MS. Selected ion
      monitoring provided useful structural information of the underivatized glycans
      from fragmentation spectra. New complex fish serum glycans that are not reported
      previously were observed and characterized. These methods may be useful not only
      for the characterization of acetylation of complex glycans but also to study
      other types of glycan modifications, as well as to allow determination of overall
      glycan composition in glycoproteins.

PMID- 22971168
TI  - Paramedic attitudes regarding prehospital analgesia.
AB  - INTRODUCTION: Although pain is a major reason why patients summon emergency
      medical services (EMS), prehospital medical providers administer analgesic agents
      at inappropriately low rates. One possible reason is the role of EMS provider
      attitudes. OBJECTIVE: This study was conducted to elicit attitudes that may act
      as impediments or deterrents to administering analgesia in the prehospital
      environment. METHODS: A qualitative methodology was employed. We recruited
      experienced paramedics, with at least one year of full-time fieldwork, from a
      variety of agencies in New England. We sought to include a balance of rural and
      urban as well as both private and hospital-based agencies. Participants at each
      site were selected through purposive sampling. A semistructured discussion guide
      was designed to elicit the paramedics' past experiences with administering
      analgesia, as well as reflections on their role in the care of patients in pain.
      Both interviews and focus groups were conducted. These sessions were recorded and
      transcribed verbatim. The transcripts were topic-analyzed and iteratively coded
      by two independent investigators utilizing the constant comparative method of
      Glaser and Strauss' Grounded Theory; coding ambiguities were resolved by
      consensus. Through a series of conceptual mapping and iterative code refinement,
      themes and domains were generated. RESULTS: Fifteen paramedics from five EMS
      agencies in three New England states were recruited. Major themes were: 1) a
      reluctance to administer opioids to patients without significant objective signs
      (e.g., deformity, hypertension); 2) a preoccupation with potential malingering;
      3) ambivalence about the degree of pain control to target or to expect (e.g.,
      aiming to "take the edge off"); 4) a fear of masking diagnostic symptoms; and 5)
      an aversion to aggressive dosing of opioids (e.g., initial doses of morphine did
      not exceed 5 mg). CONCLUSIONS: A number of potentially modifiable attitudinal
      barriers to appropriate pain management were revealed.

PMID- 22971169
TI  - Chronotype and PERIOD3 variable number tandem repeat polymorphism in individual
      sports athletes.
AB  - A link between diurnal preference and a variable number tandem-repeat (VNTR)
      polymorphism in the PERIOD3 gene (PER3) has been demonstrated: the longer PER3(5)
      and shorter PER3(4) alleles with preferences for mornings and evenings,
      respectively. As many competitive events in South Africa for individual athletes
      are scheduled for the early mornings, we hypothesized that this might favor those
      athletes with a preference for morning activities. Self-selected white, male
      cyclists (CYC, n = 125), runners (RUN, n = 120) and Ironman triathletes (IM, n =
      287) of European descent were compared with a control population of active, non
      competitive individuals (CON, n = 96). The chronotypes of all CYC, RUN and CON
      participants and a sub-sample of the IM group (n =  49) were assessed using the
      Horne-Ostberg Morningness-Eveningness Questionnaire, and the PER3 VNTR genotype
      for each participant was determined. The athlete groups contained more morning
      type individuals than the CON group (CYC: 72%, n = 90; RUN: 67%, n = 80; IM: 59%,
      n = 29; CON: 41%, n = 39; p <  .001). The prevalence of the PER3(5) allele was
      greater in the athlete groups (CYC: 61%, n =  152; RUN: 58%, n = 132; IM: 56%, n
      = 324; CON: 38%, n = 76; p <  .001), and more athletes were genotyped as
      PER3(5/5) than CON individuals (CYC: 41%, n = 51; RUN: 23%, n = 26; IM: 28%, n =
      81, CON: 9%, n = 8; p <  .001). A strong relationship between chronotype and PER3
      VNTR genotype was observed (p <  .001). Finally, the time of day at which the
      athletes preferred to train was related to their chronotype (p <  .001). This is
      the first study of its kind in a South African sporting population, and the
      results have not yet been replicated. These data suggest that white males of
      European descent participating in individual endurance sports in South Africa are
      more likely to be morning types. Furthermore, the PER3 VNTR may be one of the
      factors contributing to this observation.

PMID- 22971170
TI  - Search for seasonal rhythmicity of pineal melatonin production in rats under
      constant laboratory conditions: spectral chronobiological analysis, and relation
      to solar and geomagnetic variables.
AB  - Earlier we reported that in a number of experiments pineal melatonin production
      in rats under constant laboratory conditions displayed seasonal rhythms but
      subsequently were not always able to confirm this. Since there was no indication
      under which conditions such rhythms may be present, we performed four consecutive
      identical experiments with untreated female Sprague-Dawley rats within the same
      animal room during 1997-2006. Nocturnal urine samples (19-23, 23-3, 3-7 h) were
      collected at monthly intervals over 494-658 d with 12 animals each in experiments
      I and II (1997-1999, 1999-2000), 30 animals in experiment III (2002-2004), and 15
      in experiment IV (2005-2006). 6-Sulfatoxymelatonin (aMT6s) was measured by ELISA.
      The excreted aMT6s at each time interval as well as total nocturnal aMT6s
      excretion (19-7 h) was submitted to standard statistical analyses as well as to a
      spectral chronobiological analysis to determine the period lengths of the
      components involved which was followed by processing with the single cosinor
      method. Seasonal rhythm components (circannual period length: 360 +/- 60 d) were
      detected in experiment III (2002-2004) for the overall nocturnal excretion as
      well as for two sub-intervals (23-3 and 3-7 h) and in one night interval of
      experiment II (23-3 h). Multiple components with mostly short period lengths of
      around 100 d and some long ones of 500-650 d were found in the other experiments.
      Systematic MESOR and amplitude variations were observed during the experiments,
      being highest in experiment II (19-7 h, also 23-3 h and 3-7 h) and lowest in
      experiments I and IV. These results illustrate that seasonal melatonin rhythms
      are not a general phenomenon in female laboratory rats indicating an involvement
      of unknown environmental cues. As an extension of our earlier hypothesis
      regarding a seasonal Zeitgeber function of the horizontal intensity H of the
      geomagnetic field showing circannual variations, we assume further modulation by
      the 11-yrs' sunspot cycle which leads to geomagnetic disturbances and could
      facilitate seasonal aMT6s rhythmicity during specific years.

PMID- 22971172
TI  - Nonspecific interactions between Escherichia coli NikR and DNA are critical for
      nickel-activated DNA binding.
AB  - The Escherichia coli transcription factor NikR is responsible for nickel-mediated
      repression of the operon encoding the Nik uptake transporter. The crystal
      structure of Ni(II)-NikR bound to the nik operator sequence revealed that
      residues in the loop preceding helix alpha3 in the metal-binding domain, which
      becomes structurally ordered upon stoichiometric nickel binding, interact with
      the DNA backbone. Here, we show that mutating both of these residues that make
      the nonspecific contacts, K64 and R65, abolishes DNA binding in vitro and nickel
      responsive transcriptional repression of the nik promoter in vivo. In contrast,
      mutation of Q118, which forms a bridge between R65 and a potassium site, does not
      impact the activities of NikR. These data support the model that the nonspecific
      interactions between the metal-binding domain of the protein and the DNA
      phosphodiester backbone are critical for the Ni(II)-responsive activity of E.
      coli NikR.

PMID- 22971173
TI  - High pressure-high temperature decomposition of gamma-cyclotrimethylene
      trinitramine.
AB  - Decomposition of gamma-cyclotrimethylene trinitramine (gamma-RDX) under high
      pressure-high temperature conditions was examined to elucidate the reactive
      behavior of RDX crystals. Vibrational spectroscopy measurements were obtained for
      single crystals in a diamond anvil cell (DAC) at pressures from 6 to 12 GPa and
      temperatures up to 600 K. Global decomposition rates, activation energies, and
      activation volumes at several pressures and temperatures below the P-T locus for
      the gamma-RDX decomposition were obtained. Similar to epsilon-RDX, but in
      contrast to alpha-RDX, we found that pressure decelerates the decomposition of
      gamma-RDX. The decomposition deceleration with pressure in the gamma-phase can be
      attributed to pressure-inhibiting bond homolysis step(s). The main decomposition
      species were identified as N(2)O, CO(2), and H(2)O, in accord with the species
      reported for the alpha-phase decomposition at high pressures. This work
      complements previous studies on RDX at HP-HT conditions and provides
      comprehensive results on the reactive behavior of gamma-RDX; the gamma-phase
      plays a key role in RDX decomposition at P-T conditions relevant to shock wave
      initiation.

PMID- 22971174
TI  - Multiple cytokine-producing plasmablastic solitary plasmacytoma of bone
      expressing multiple cytokine receptors.

PMID- 22971175
TI  - Mechanical and free living comparisons of four generations of the Actigraph
      activity monitor.
AB  - BACKGROUND: More studies include multiple generations of the Actigraph activity
      monitor. So far no studies have compared the output including the newest
      generation and investigated the impact on the output of the activity monitor when
      enabling the low frequency extension (LFE) option. The aims were to study the
      responses of four generations (AM7164, GT1M, GT3X and GT3X+) of the Actigraph
      activity monitor in a mechanical setup and a free living environment with and
      without enabling the LFE option. METHODS: The monitors were oscillated in a
      mechanical setup using two radii in the frequency range 0.25-3.0 Hz. Following
      the mechanical study a convenience sample (N = 20) wore three monitors (one
      AM7164 and two GT3X) for 24 hours. RESULTS: The AM7164 differed from the newer
      generations across frequencies (p < 0.05) in the mechanical setup. The AM7164
      produced a higher output at the lower and at the highest intensities, whereas the
      output was lower at the middle intensities in the mid-range compared to the newer
      generations. The LFE option decreased the differences at the lower frequencies,
      but increased differences at the higher. In free living, the mean physical
      activity level (PA) of the GT3X was 18 counts per minute (CPM) (8%) lower
      compared to the AM7164 (p < 0.001). Time spent in sedentary intensity was 26.6
      minutes (95% CI 15.6 to 35.3) higher when assessed by the GT3X compared to the
      AM7164 (p < 0.001). Time spend in light and vigorous PA were 23.3 minutes (95% CI
      31.8 to 14.8) and 11.7 minutes (95% CI 2.8 to 0.7) lower when assessed by the
      GT3X compared to the AM7164 (p < 0.05). When enabling the LFE the differences in
      the sedentary and light PA intensity (<333 counts*10 sec-1) were attenuated (p >
      0.05 for differences between generations) thus attenuated the difference in mean
      PA (p > 0.05) when the LFE option was enabled. However, it did not attenuate the
      difference in time spend in vigorous PA and it introduced a difference in time
      spend in moderate PA (+ 3.0 min (95% CI 0.4 to 5.6)) between the generations.
      CONCLUSION: We observed significant differences between the AM7164 and the newer
      Actigraph GT-generations (GT1M, GT3X and GT3X+) in a mechanical setup and in free
      living. Enabling the LFE option attenuated the differences in mean PA completely,
      but induced a bias in the moderate PA intensities.

PMID- 22971177
TI  - Elimination and active extrusion of liver mitochondrial proteins during
      lipopolysaccharide administration in rat.
AB  - AIM: The purpose of the present study was to identify molecular markers of
      hepatic damage during lipopolysaccharide (LPS) treatment. METHODS: LPS (15 mg/kg
      of bodyweight) or vehicle was injected i.p. into 5-week-old male Sprague-Dawley
      rats. Proteins were extracted from the liver and were electrophoresed to examine
      the changes in the protein compositions during LPS treatment. Using a proteomic
      approach, major LPS-responsible protein in the liver was determined. RESULTS: A
      massive reduction in the levels of carbamoyl phosphate synthase-1 (CPS1), one of
      the most abundant proteins in liver mitochondria, was revealed during LPS
      administration. Electron microscopic and immunofluorescence analyses revealed
      large vacuoles, which were often localized in the vicinity of mitochondria, in
      the LPS-treated rat liver. Furthermore, we found that CPS1 is released into the
      circulation prior to liver damage marker alanine aminotransferase, indicating the
      active extrusion of CPS1 during LPS administration. Another liver mitochondrial
      protein, ornithine transcarbamylase, is also released into the circulation,
      implicating active extrusion of mitochondrial proteins. These phenomena are
      accelerated by a heme oxygenase inducer cobalt protoporphyrin whilst suppressed
      by a lysosome inhibitor chloroquine. CONCLUSION: Plasma CPS1 should be a possible
      marker of septic liver damage and may be involved in systemic responses elicited
      by septic shock.

PMID- 22971176
TI  - Determinants of pregnant women's compliance with alcohol guidelines: a
      prospective cohort study.
AB  - BACKGROUND: In 2009, Australian alcohol guidelines for pregnancy changed from low
      to no alcohol intake. Previous research found a high proportion of pregnant
      Australian women drank during pregnancy; however, there has been limited
      investigation of whether pregnant women comply with 2009 alcohol guidelines. The
      purpose of this study was to provide an assessment of pregnant women's compliance
      with 2009 Australian alcohol guidelines and identify predictors of such
      compliance, including previous drinking behaviour. METHODS: Cross-sectional
      analysis of prospective data from the 1973-1978 cohort of the Australian
      Longitudinal Study on Women's Health was conducted. Women aged 30-36 years who
      were pregnant at the 2009 survey and had data on alcohol use were included (n =
      837). Compliance with 2009 alcohol guidelines for pregnancy was defined as no
      alcohol intake. Predictors of compliance were analysed using multivariate
      logistic regression, controlling for area of residence, in three separate models
      to account for multicollinearity between measures of previous alcohol intake
      (compliance with 2001 guidelines; frequency and quantity; bingeing). Private
      health insurance, household income, and illicit drug use were entered into all
      models and retained if significant. RESULTS: 72% of pregnant women did not comply
      with the 2009 alcohol guidelines and 82% of these women drank less than seven
      drinks per week, with no more than one or two drinks per drinking day. The odds
      of complying with abstinence increased by a factor of 3.48 (95% CI 2.39-5.05) for
      women who previously complied with the 2001 alcohol guidelines and decreased by a
      factor of 0.19 (95% CI 0.08-0.66) if household incomes were $36,400 or more. In
      other models the odds of complying were lower for women who consumed alcohol
      before pregnancy at least weekly (OR = 0.40, 95% CI 0.25-0.63) or binged (OR >=
      0.18, 95% CI 0.10-0.31) and were higher for those who abstained (OR = 45.09; 95%
      CI 8.63-235.49) prior to pregnancy. CONCLUSION: Most pregnant women did not
      comply with alcohol guidelines promoting abstinence. Prior alcohol behaviour was
      the strongest predictor of compliance during pregnancy, suggesting alcohol use
      should be addressed in women of child-bearing age. The study is limited by the
      relatively short timeframe between the official introduction of the 2009
      guidelines and the date the surveys were sent out. Widespread dissemination of
      the guidelines may be necessary to help increase guideline compliance by pregnant
      women.

PMID- 22971178
TI  - Quinoxaline derivatives: a patent review (2006--present).
AB  - INTRODUCTION: Quinoxaline scaffold is included in a large number of therapeutic
      agents because of its physicochemical properties that make the difference between
      them and the carbono analogue, naphthalene. AREAS COVERED: This review of
      patented products presents the quinoxaline heterocycle as part of the structural
      patent claims from a medicinal chemistry perspective. EXPERT OPINION: We centred
      our discussion in the various drug patent applications of the quinoxaline and its
      derivatives. The applications are based firstly in the specific enzyme target
      with very low development in the disease treatment. Only for cancer and
      antimicrobial agents they were specifically determined but little is mentioned in
      order to insight in the last development activities.

PMID- 22971181
TI  - An unusual case of predation: dog pack or cougar attack?
AB  - Injuries produced by animals are capable of leaving severe patterns and in some
      cases may result in the death of the attacked individual. Law enforcement
      authorities may come to erroneous conclusions about the source of the bites based
      on their awareness of animals present and similarities of the injuries to the
      untrained eye, with dreadful consequences. Expertise of a carnivore biologist and
      an odontologist that indentifies the particularities of bite marks may be useful
      for identifying the attacking species. We present the investigation of a fatal
      dog pack attack involving a 43-year-old man in Bell Ville (Argentina) where the
      evidence provided by a forensic dentist and a biologist was categorical for
      establishing the animal species involved. Because of the unusual characteristics
      of the wounds and the initial hypothesis made by local authorities of a cougar
      attack, habits and specific patterns of both dog pack and cougar predation on
      humans are discussed.

PMID- 22971182
TI  - Europe debates circumcision...and what about the child's best interest?

PMID- 22971183
TI  - Efficient magnesium catalysts for the copolymerization of epoxides and CO2; using
      water to synthesize polycarbonate polyols.
AB  - The synthesis and characterization of three highly active dimagnesium catalysts
      for the copolymerization of cyclohexene oxide and carbon dioxide, active under
      just 1 atm of carbon dioxide pressure, are reported. The catalysts have turnover
      numbers up to 6000 and turnover frequencies of up to 750 h(-1). These values are,
      respectively, 75 and 20 times higher than those of the other three known
      magnesium catalysts. Furthermore, the catalysts operate at 1/500th the loading of
      the best reported magnesium catalyst. The catalyst selectivities are excellent,
      yielding polymers with 99% carbonate repeat units and >99% selectivity for
      copolymer. Using a dimagnesium bis(trifluoroacetate) catalyst, and water as a
      renewable chain transfer reagent, poly(cyclohexene carbonate) polyols are
      synthesized with high selectivity.

PMID- 22971184
TI  - Power prediction for one-piece and three-piece intraocular lens implantation
      after cataract surgery in patients with chronic angle-closure glaucoma: a
      prospective, randomized clinical trial.
AB  - PURPOSE: To assess the accuracy of intraocular lens (IOL) power prediction for
      cataract surgery in chronic angle-closure glaucoma (CACG) patients with different
      IOLs' implantation. METHODS: This prospective randomized clinical trial included
      45 eyes with CACG and 48 eyes with normal controls undergoing cataract surgery.
      In the CACG group, 23 eyes (51%) had three-piece IOL implantation and 22 eyes
      (49%) had one-piece IOL implantation. In the normal control group, 25 eyes (52%)
      had three-piece IOL implantation and 23 eyes (48%) had one-piece IOL
      implantation. Using the SRK/T formula, the mean difference between the predicted
      and actual postoperative spherical equivalent [mean absolute error (MAE)] was
      obtained and converted to natural logarithm (ln) for statistical analysis. The
      power of the implanted IOL was calculated to predict postoperative SE using three
      formulas: SRK II, Holladay II and Hoffer Q by post hoc analysis in each group.
      The predictive accuracy of each formula was analysed by comparing the lnMAE.
      RESULTS: In the one-piece IOL group, there was no difference in lnMAE between the
      CACG and normal control group (p = 0.314). In the three-piece IOL group, the
      lnMAE of the CACG group was larger than that of the normal control group (p <
      0.001). The lnMAEs calculated by the SRK/T formula were more accurate than the
      Holladay II (p = 0.045) and Hoffer Q (p = 0.042) formula in the CACG one-piece
      IOL group. CONCLUSIONS: Implantation of one-piece IOLs provides similar power
      prediction accuracy comparable to normal cataract patients; this result may be
      explained by the IOL haptic configuration or design.

PMID- 22971185
TI  - Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres
      with low toxicity.
AB  - OBJECTIVES: The aim of this study was to perform a systematic preclinical
      evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM).
      RESEARCH DESIGN AND METHODS: Pharmacokinetics, biodistribution, antitumor
      efficacy and drug safety assessment (including acute toxicity, subchronic
      toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis)
      of NLM were carried out in comparison with the commercial product disodium
      norcantharidate injection (NI). RESULTS: The pharmacokinetics of NLM in rats was
      similar to that of NI, and a non-linear correlation was observed between AUC and
      dose. A comparable antitumor efficacy of NLM and NI was observed in mice
      inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that
      the NLM produced a lower drug concentration in heart compared with NI, and
      significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice
      higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or
      bound with phospholipids. Thus, NCTD was sequestered by direct contacting with
      body fluids and largely avoided distribution into tissues, consequently leading
      to significantly reduced cardiac and renal toxicity. CONCLUSIONS: These
      preclinical results suggested that NLM could be a useful potential carrier for
      parenteral administration of NCTD, while providing a superior safety profile.

PMID- 22971186
TI  - From the bottle to the skin: challenges in evaluating antioxidants.
AB  - Endogenous production and ultraviolet-generated free radicals in the skin can
      lead to photoaging and even skin cancer. Topical antioxidants have been found to
      provide benefits against ultraviolet damage and these ingredients have been
      incorporated into various cosmetic products and claimed to have substantial
      effects. Currently, there is a lack in a standardized rating system to measure
      the concentration and activity levels of antioxidants in these products. As a
      result, it is difficult for consumers and clinicians to evaluate and select
      commercial products based on readily accessible evidence. In this review, we will
      describe four assays which have been used to measure antioxidants in various
      products, and the strengths and weaknesses of each test will be detailed. We will
      highlight key considerations for clinicians when interpreting the results of
      antioxidant tests when evaluating commercial products containing antioxidants.

PMID- 22971187
TI  - Ambulatory photodynamic therapy using low irradiance inorganic light-emitting
      diodes for the treatment of non-melanoma skin cancer: an open study.
AB  - BACKGROUND/PURPOSE: Conventional photodynamic therapy (PDT) can be inconvenient
      and uncomfortable. We studied low irradiance PDT using an ambulatory inorganic
      light-emitting diode. METHODS: Fifty-three patients with 61 lesions [superficial
      basal cell carcinoma (n = 30), Bowen's disease (n = 30), and actinic keratosis
      (AK; n = 1)] were studied. Two treatments of ambulatory PDT were undertaken 1
      week apart (one treatment for AK). Clinical response was determined at 3 months,
      and the treatment cycle was repeated if there was residual disease. The endpoints
      assessed were pain during treatment (numerical rating scale (NRS); 0-10) and
      outcome at 1 year. Twenty-three of these patients also received conventional PDT
      to separate lesions. RESULTS: The median NRS pain scores during first and second
      treatment were 2 (range 0-9) and 4 (0-9), respectively. Lesion clearance rate at
      1 year after ambulatory PDT was 84% (21/25 lesions in 22 patients). Of the twenty
      three patients treated with both ambulatory and conventional PDT, the median NRS
      was 1 (0-7) and 5 (1.5-9), respectively, with most patients preferring ambulatory
      PDT. CONCLUSION: Ambulatory PDT is effective for superficial non-melanoma skin
      cancer, with 1 year clearance rates comparative to conventional PDT. Low
      irradiance ambulatory PDT may be less painful and more convenient than
      conventional PDT.

PMID- 22971188
TI  - Influence of the quantity of sunscreen applied on the ability to protect against
      ultraviolet-induced polymorphous light eruption.
AB  - BACKGROUND/PURPOSE: Despite the fact that most people apply less sunscreen than
      the 2 mg/cm(2)  required to measure sun protection factor (SPF), there is a lack
      of clinical data on the protection afforded from lower applied quantities. The
      aim of this study was to compare the ability of sunscreens to protect against UV
      induced polymorphous light eruption (PLE) when applied at 2 mg/cm(2)  and 1
      mg/cm(2) . METHODS: Two SPF 45 sunscreens (one with a high level and one with a
      low level of UVA protection) were applied at 2 mg/cm(2)  and 1 mg/cm(2)  to four
      randomized 6 * 6 cm areas on the upper thorax of 15 female patients with a
      typical history of PLE. The areas were exposed daily to increasing UVA-UVB
      radiation until a PLE reaction was detected or a maximum of five consecutive
      days. RESULTS: The proportion of patients who developed a PLE reaction with the
      high UVA-protection sunscreen was significantly lower (0%) than with the low UVA
      protection sunscreen (73%) when both sunscreens were applied at 2 mg/cm(2)  (P =
      0.004). At 1 mg/cm(2) , 33% and 80% of patients presented a PLE reaction with the
      high and low UVA-protection sunscreen, respectively (P = 0.064). CONCLUSION: A
      high SPF and high UVA-protection broad spectrum sunscreen was able to protect the
      majority of patients from the development of UV-induced PLE reaction even at 1
      mg/cm(2) .

PMID- 22971189
TI  - Comparison of sunscreen availability in Chicago Hispanic and non-Hispanic
      neighborhoods.
AB  - BACKGROUND: Poorer survival rates from melanoma among Hispanics have been
      previously reported. There is little information regarding sunscreen acquisition
      behaviors or availability/access to products that may help reduce the risk of
      skin cancer in Hispanic communities. This study sought to understand perceptions
      regarding sun protection and skin cancer risk and whether the availability of
      over-the-counter sunscreen products differed in three Chicago neighborhoods with
      different ethnic compositions. METHODS: We drew on interviews with 65 adult
      Spanish speaking Hispanics (23-72 years) recruited from faith-based institutions
      to better understand sunscreen use perceptions. Commercial establishments open to
      the general public were physically canvassed to determine whether there were any
      differences in sunscreen products availability. RESULTS: Stores carrying sun
      protection products are nearly twice as common in non Hispanic White
      neighborhoods versus Hispanic. In addition, when sunscreens are available for
      sale, Hispanics have fewer sunscreens to choose from. DISCUSSION: Emergent themes
      that were elicited during the interviews revealed that barriers to increased
      sunscreen use include economic and erroneous perceptions regarding skin cancer
      incidence and risk. Environmental factors that may reinforce these beliefs
      include lower availability and variety of sun protection products in Hispanic
      neighborhoods. CONCLUSION: These findings indicate that providing culturally
      appropriate public health information encouraging the use of sunscreen and
      improving its availability in Hispanic communities are potential points of
      intervention in attempts to improve morbidity from skin cancer.

PMID- 22971191
TI  - Ciprofloxacin-induced phototoxicity in an adult cystic fibrosis population.
AB  - The incidence of phototoxicity as a side effect of ciprofloxacin appears to be
      increased in patients with cystic fibrosis compared to the general population
      (approximately 2.4%). We used an interview-based questionnaire to determine the
      incidence of such phototoxic skin reactions in cystic fibrosis patients. Results
      from 105 respondents revealed the incidence of ciprofloxacin-induced
      phototoxicity in the adult cystic fibrosis population in Northern Ireland to be
      48.4% with only 66% of the patients recalling being given sun care information
      beforehand. We concluded that the incidence of phototoxicity is increased in
      patients with cystic fibrosis and that it is important for all to receive good
      sun care information prior to taking ciprofloxacin given the high risk of
      developing phototoxic rash.

PMID- 22971190
TI  - Long-term follow-up and survival of cutaneous T-cell lymphoma patients treated
      with extracorporeal photopheresis.
AB  - PURPOSE: Extracorporeal photopheresis (ECP) is effective for treating cutaneous T
      cell lymphoma. In 1987, a pivotal trial showed 81% overall response rate (ORR)
      using outdated criteria. No long-term follow-up was available for assessing
      survival. This study applies modern criteria to the 1987 trial to assess the
      impact of ECP on skin responses and also updates overall survival of the cohort.
      METHODS: Generalized erythroderma (GE, stage T4, n = 31) or extensive patch
      plaque (EPP, stage T2, n = 8) patients received ECP (mean 3.9 years' duration).
      Patients achieving >= 50% partial skin response, >= 90% near-complete skin
      response, treatments required, and duration of response (DOR) were determined.
      Overall survival (OS) from diagnosis and first ECP treatment was determined for
      all patients and the GE cohort. RESULTS: Patients showed 74% skin ORR using
      modern criteria; 33% of patients achieved >= 50% partial skin response (after
      median 7.1 months, mean 23 ECP treatments); 41% achieved >= 90% improvement
      (after median 19.6 months, mean 40 ECP treatments). Mean DOR was 14 months for >=
      50% improvement and 8.9 months for >= 90% improvement. Response rates were
      comparable for GE and EPP cohorts. Median OS was 9.2 years from diagnosis and 6.6
      years from ECP initiation (71.6 months follow-up). CONCLUSION: Analysis of long
      term follow-up confirmed durable responses and prolonged survival of patients
      treated with ECP.

PMID- 22971192
TI  - Phototolerance induced by narrow-band UVB phototherapy in severe erythropoietic
      protoporphyria.
AB  - Erythropoietic protoporphyria arises from an inherited disorder of porphyrin
      metabolism which leads to an accumulation of protoporphyrin IX in the
      erythropoietic system and other tissues. It is characterized by cutaneous
      photosensitivity, usually difficult to keep under control. Among the scant
      therapeutic options proposed to reduce photosensitivity in erythropoietic
      protoporphyria, narrow-band UVB phototherapy has occasionally been used to induce
      sunlight tolerance. We report an adult case of erythropoietic protoporphyria with
      a severe photosensitivity treated with narrow-band UVB that developed an
      appropriate sunlight phototolerance, without adverse events during phototherapy.

PMID- 22971193
TI  - Successful treatment of generalized elastolytic giant cell granuloma with
      psoralen-ultraviolet A.
AB  - Elastolytic giant cell granuloma (EGCG) is an infrequent granulomatous skin
      disorder with variable response to different therapeutic regimens. Information on
      the benefit of phototherapy is very scarce as this therapy has seldom been tried
      in the affected patients. We present the results achieved in two female patients
      after undergoing psoralen-ultraviolet A (PUVA). Two 54-year-old otherwise healthy
      female patients received a course of PUVA after trying other alternatives.
      Complete clearance was achieved in the two patients with excellent tolerance and
      no adverse effects. We consider PUVA is a well-tolerated, safe, and effective
      treatment for patients with EGCG.

PMID- 22971194
TI  - Narrowband UVB as an effective substitute for psoralen plus UVA: lessons from a
      psoralen shortage.
AB  - From March to August 2010, there was a shortage of encapsulated liquid 8
      methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in
      Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were
      transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A
      retrospective chart review was conducted of all patients who discontinued bath
      PUVA due to the unavailability of 8-MOP, with a focus on those who were switched
      to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to
      nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to
      nbUVB improved, and patients with earlier-stage disease were more likely to
      improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two
      patients whose psoriasis cleared completely. All three small-plaque parapsoriasis
      patients who switched to nbUVB had complete clearance of their lesions. In
      conclusion, nbUVB may be a suitable alternative for patients with MF, small
      plaque parapsoriasis and psoriasis who cannot access PUVA therapy.

PMID- 22971195
TI  - Genetic study in a Singaporean patient with erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haem
      biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity
      which leads to the excessive accumulation of protoporphyrin in blood,
      erythrocytes and tissues. Cutaneous manifestations of photosensitivity usually
      appear in early infancy upon the first sun exposures. This normally requires the
      co-inheritance of a common hypomorphic FECH allele and a deleterious FECH
      mutation. Here, we report the first Singaporean Chinese patient with EPP
      characterized at the molecular level.

PMID- 22971196
TI  - Is the pain of topical photodynamic therapy with methyl aminolevulinate any
      different from that with 5-aminolaevulinic acid?
AB  - Topical photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) or methyl
      aminolevulinate (MAL) is widely used in dermatology. It is commonly stated that
      MAL PDT is less painful than ALA PDT, although published data are conflicting. We
      report our experience of the use of ALA (4-6 h) (n = 20) and MAL (3 h) (n = 20)
      in 40 consecutive patients with Bowen's disease or superficial basal cell
      carcinoma, treated with PDT using an identical irradiation regime. Although there
      was a trend to higher pain scores with ALA PDT [visual analogue scale (VAS)score,
      median 4.50], this was not significantly different from that of MAL PDT (VAS
      score, median 3.55; P = 0.98), nor considered to be clinically important.
      Importantly, both ALA and MAL PDT regimes were fairly well tolerated in this
      patient cohort, supporting the use of these prodrugs in dermatological PDT.

PMID- 22971197
TI  - Broad band UVA: a possible reliable alternative to PUVA in the treatment of early
      stage mycosis fungoides.
AB  - UVA1 phototherapy was found to induce marked improvement in skin lesions of
      patients with stages IA and IB mycosis fungoides (MF). Broad band UVA (BB-UVA) is
      composed of 80.1% UVA1, with similar mechanisms of action. Our aim was to
      evaluate the efficacy of BB-UVA in the treatment of early-stage MF. Thirty
      patients with early stage MF were included. They were divided into two equal
      groups receiving either BB-UVA at 20 J/cm2/ session or PUVA three times/week for
      40 sessions. Clinical and histopathological evaluations were performed before and
      after therapy in addition to immunohistochemical measurement of CD4+ cells and
      Bcl-2. Patients were followed up for an average duration of 36 months. Comparable
      clinical and histopathological improvement was noted in MF patients in both
      groups. Clinical improvement graded 'Excellent' was achieved in 33% of patients
      in the BB-UVA versus 13.3% in the psoralen and UVA (PUVA) group. Long-term follow
      up indicated superiority of BB-UVA over PUVA. BB-UVA group showed a more rapid
      clearance rate, shorter time to achieve complete clearance, a longer disease-free
      interval and lower relapse rate. The use of BB-UVA in the treatment of early
      stage MF is comparable or even superior to PUVA regarding efficacy and remission
      periods.

PMID- 22971198
TI  - Development of new lesions: a complication of psoralen plus ultraviolet A light
      therapy for mycosis fungoides.

PMID- 22971200
TI  - Testosterone deficiency in men: systematic review and standard operating
      procedures for diagnosis and treatment.
AB  - INTRODUCTION: Testosterone (T) deficiency (TD) may significantly affect sexual
      function and multiple organ systems. AIM: To provide recommendations and Standard
      Operating Procedures (SOPs) based on best evidence for diagnosis and treatment of
      TD in men. METHODS: Medical literature was reviewed by the Endocrine subcommittee
      of the ISSM Standards Committee, followed by extensive internal discussion over
      two years, then public presentation and discussion with other experts. MAIN
      OUTCOME MEASURE: Recommendations and SOPs based on grading of evidence-based
      medical literature and interactive discussion. RESULTS: TD is the association of
      a low serum T with consistent symptoms or signs. T level tends to decline with
      age. T modulates sexual motivation and erection. It also plays a broader role in
      men's health. Recent studies have established associations between low T, male
      sexual dysfunctions and metabolic risk factors. Though association does not mean
      causation, low T is associated with reduced longevity, risk of fatal
      cardiovascular events, obesity, sarcopenia, mobility limitations, osteoporosis,
      frailty, cognitive impairment, depression, Sleep Apnea Syndrome, and other
      chronic diseases. The paper proposes a standardized process for diagnosis and
      treatment of TD, and updates the knowledge on T therapy (Tth) and prostate and
      cardiovascular safety. There is no compelling evidence that Tth causes prostate
      cancer or its progression in men without severe TD. Polycythemia is presently the
      only cardiovascular-related adverse-event significantly associated with Tth. But
      follow-up of controlled T trials is limited to 3 years. CONCLUSIONS: Men with
      sexual dysfunctions, and/or with visceral obesity and metabolic diseases should
      be screened for TD and treated. Young men with TD should also be treated.
      Benefits and risks of Tth should be carefully assessed in older men. Prospective,
      long-term, placebo-controlled, interventional studies are required before
      screening for TD in more conditions, including cardiovascular diseases, and
      considering correction of TD as preventive medicine.

PMID- 22971201
TI  - Transcriptome classification reveals molecular subtypes in psoriasis.
AB  - BACKGROUND: Psoriasis is an immune-mediated disease characterised by chronically
      elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte
      proliferation and differentiation. Although certain clinical phenotypes, such as
      plaque psoriasis, are well defined, it is currently unclear whether there are
      molecular subtypes that might impact on prognosis or treatment outcomes. RESULTS:
      We present a pipeline for patient stratification through a comprehensive analysis
      of gene expression in paired lesional and non-lesional psoriatic tissue samples,
      compared with controls, to establish differences in RNA expression patterns
      across all tissue types. Ensembles of decision tree predictors were employed to
      cluster psoriatic samples on the basis of gene expression patterns and reveal
      gene expression signatures that best discriminate molecular disease subtypes.
      This multi-stage procedure was applied to several published psoriasis studies and
      a comparison of gene expression patterns across datasets was performed.
      CONCLUSION: Overall, classification of psoriasis gene expression patterns
      revealed distinct molecular sub-groups within the clinical phenotype of plaque
      psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the
      two psoriasis subgroups, suggested that this group may be more amenable to
      therapies targeting these pathways. Our study highlights the potential biological
      relevance of using ensemble decision tree predictors to determine molecular
      disease subtypes, in what may initially appear to be a homogenous clinical group.
      The R code used in this paper is available upon request.

PMID- 22971203
TI  - Treatment of vitamin D deficiency within a large integrated health care delivery
      system.
AB  - BACKGROUND: In the past decade, increasing attention has focused on
      identification and treatment of vitamin D deficiency although repletion outcomes
      of pharmacologic vitamin D therapy have not been examined at a population level.
      OBJECTIVE: To investigate population trends and outcomes of pharmacologic
      treatment of vitamin D deficiency. METHODS: We conducted a retrospective cohort
      study using data from an integrated health system with approximately 3.2 million
      members. Automated laboratory and pharmacy databases were used to identify
      patients aged 18 years or older with hypovitaminosis D (defined as a 25-hydroxy
      vitamin D [25(OH)D] serum level < 20 nanograms [ng] per mL) who newly initiated
      pharmacologic ergocalciferol (50,000 international units [IU] per week) during
      2007-2010 and did not have a prescription for ergocalciferol in the prior 12
      months. Patients were required to be continuously enrolled for 12 months before
      and 6 months after ergocalciferol initiation. Age, gender, race/ethnicity, body
      mass index, and 25(OH)D levels were obtained from health plan electronic medical
      records and administrative, laboratory, and pharmacy databases. Outcome and
      predictors of repletion among the subset who received 12 weekly doses of 50,000
      IU ergocalciferol (total dose 600,000 IU) were examined using multivariable
      logistic regression. RESULTS: There were 72,093 vitamin D-deficient patients who
      newly initiated pharmacologic ergocalciferol. During the study period, the use of
      ergocalciferol increased nearly 8-fold from 161 per 100,000 adult members in 2007
      to 1,241 per 100,000 adult members in 2010. One-fifth (n = 14,727) had severe
      vitamin D deficiency (25[OH]D level < 10 ng per mL). Among 23,322 patients
      receiving 50,000 IU ergocalciferol for 12 weeks in whom subsequent 25(OH)D levels
      were measured between 90 and 365 days after the index ergocalciferol prescription
      date, 74.0% achieved 25(OH)D of at least 20 ng per mL, and 35.8% achieved 25(OH)D
      of at least 30 ng per mL. Increasing age (adjusted odds ratio [OR] 1.02, 95% CI
      1.02-1.02) and higher baseline 25(OH)D level (OR 1.11, 95% CI 1.10-1.12) were
      associated with greater odds of successful repletion. Asian race (OR 0.80, 95% CI
      0.73-0.88), Hispanic ethnicity (OR 0.71, 95% CI 0.65-0.77), and increasing
      overweight/obesity (OR 0.78, 95% CI 0.72-0.85 for body mass index [BMI], 25.0
      29.9 kg/m2; OR 0.66, 95% CI 0.60-0.71 for BMI 30.0-39.9 kg/m2; OR 0.53, 95% CI
      0.48-0.60 for BMI >= 40 kg/m2) were associated with lower odds of repletion
      compared with BMI 18.5-24.9 kg/m2. CONCLUSIONS: There is increasing recognition
      and treatment of vitamin D deficiency within the health care setting. Patients of
      younger age, Asian and Hispanic race/ethnicity, and those who are obese or with
      more severe vitamin D deficiency may be at greater risk for incomplete repletion
      using standard regimens and may require additional treatment to achieve optimal
      levels.

PMID- 22971202
TI  - Molecular modeling of the reaction pathway and hydride transfer reactions of HMG
      CoA reductase.
AB  - HMG-CoA reductase catalyzes the four-electron reduction of HMG-CoA to mevalonate
      and is an enzyme of considerable biomedical relevance because of the impact of
      its statin inhibitors on public health. Although the reaction has been studied
      extensively using X-ray crystallography, there are surprisingly no computational
      studies that test the mechanistic hypotheses suggested for this complex reaction.
      Theozyme and quantum mechanical (QM)/molecular mechanical (MM) calculations up to
      the B3LYP/6-31g(d,p)//B3LYP/6-311++g(2d,2p) level of theory were employed to
      generate an atomistic description of the enzymatic reaction process and its
      energy profile. The models generated here predict that the catalytically
      important Glu83 is protonated prior to hydride transfer and that it acts as the
      general acid or base in the reaction. With Glu83 protonated, the activation
      energies calculated for the sequential hydride transfer reactions, 21.8 and 19.3
      kcal/mol, are in qualitative agreement with the experimentally determined rate
      constant for the entire reaction (1 s(-1) to 1 min(-1)). When Glu83 is not
      protonated, the first hydride transfer reaction is predicted to be disfavored by
      >20 kcal/mol, and the activation energy is predicted to be higher by >10
      kcal/mol. While not involved in the reaction as an acid or base, Lys267 is
      critical for stabilization of the transition state in forming an oxyanion hole
      with the protonated Glu83. Molecular dynamics simulations and MM/Poisson
      Boltzmann surface area free energy calculations predict that the enzyme active
      site stabilizes the hemithioacetal intermediate better than the aldehyde
      intermediate. This suggests a mechanism in which cofactor exchange occurs before
      the breakdown of the hemithioacetal. Slowing the conversion to aldehyde would
      provide the enzyme with a mechanism to protect it from solvent and explain why
      the free aldehyde is not observed experimentally. Our results support the
      hypothesis that the pK(a) of an active site acidic group is modulated by the
      redox state of the cofactor. The oxidized cofactor and deprotonated Glu83 are
      closer in space after hydride transfer, indicating that indeed the cofactor may
      influence the pK(a) of Glu83 through an electrostatic interaction. The enzyme is
      able to catalyze the transfer of a hydride to the structurally and electronically
      distinct substrates by maintaining the general shape of the active site and
      adjusting the electrostatic environment through acid-base chemistry. Our results
      are in good agreement with the well-studied hydride transfer reactions catalyzed
      by liver alcohol dehydrogenase in calculated energy profile and reaction
      geometries despite different mechanistic functionalities.

PMID- 22971204
TI  - Long-term Medicaid excess payments from alleged price manipulation of generic
      lorazepam.
AB  - BACKGROUND: Cost savings from the use of generic drugs versus brand-name drugs
      are well known. Both private and public prescription drug plans encourage the use
      of generic drugs through a variety of mechanisms. The magnitude of cost savings
      for a given generic drug is dependent on the degree to which the generic market
      is competitive. Should the competitive structure become compromised, higher
      prices and reduced cost savings may result. An alleged conspiracy between Mylan
      Laboratories and its active-ingredient suppliers in 1997 was associated with an
      increase in seller concentration in the generic lorazepam market. The Federal
      Trade Commission (FTC) alleged that Mylan raised costs to consumers by $120
      million because of price increases for generic lorazepam from March through
      December 1998 and for generic clorazepate from January through December 1998. In
      November 2002, a settlement with Mylan was approved by the FTC, and a federal
      district court required Mylan to pay $147 million, including $28.2 million to
      state agencies including Medicaid. OBJECTIVES: To (a) describe the seller
      concentration in the national Medicaid generic lorazepam market over a 19-year
      period from January 1991 through December 2009, (b) estimate the excess payments
      for generic lorazepam by Medicaid between 1998 and 2009, and (c) investigate
      potentially increased utilization and prices of 2 substitute pharmaceuticals:
      branded lorazepam (Ativan) and generic alprazolam (another widely used
      intermediate-acting benzodiazepine). METHODS: Using Medicaid State Drug
      Utilization Data from the Centers for Medicare Medicaid Services, we calculated
      the 4-firm concentration ratio (CR4) and the Herfindahl-Hirschman Index (HHI) for
      the Medicaid generic lorazepam market, along with pre-rebate reimbursement for
      pharmacy claims, number of claims (utilization), and average pre-rebate
      reimbursement per claim (average "price") for generic lorazepam, from 1991
      through 2009. Medicaid's excess payments were estimated under 2 different
      assumptions regarding what the average generic lorazepam price would have been in
      the absence of the alleged conspiracy. To find counterfactual prices, the average
      per-claim reimbursement for lorazepam for the 4 quarters prior to the alleged
      conspiracy, $6.80, was inflated using (a) the quarterly change in the average per
      claim reimbursement for generic alprazolam and (b) the Consumer Price Index (CPI)
      for all urban consumers, all goods. Potential impact of the alleged conspiracy on
      the branded lorazepam and generic alprazolam markets was investigated. RESULTS:
      The average pre-rebate reimbursements per claim for generic lorazepam were
      $10.25, $23.12, and $8.48 in 1991, 1998, and 2009, respectively. For the same 3
      years, CR4 = 52.80, 76.02, and 86.74, while HHI = 905.71, 2,166.25, and 2,233.36.
      Medicaid's excess payments from 1998-2009 were estimated at approximately $625
      $657 million. The data also suggest the possibility of small impacts on the
      utilization of branded lorazepam and the price of generic alprazolam.
      CONCLUSIONS: Prior to the alleged conspiracy in 1997, average pre-rebate
      reimbursement per claim for generic lorazepam was declining, while seller
      concentration was rising. After a jump in average payment per claim in the years
      immediately following the alleged conspiracy, prices have gradually returned to
      their pre-1998 levels. However, the generic lorazepam market was more
      concentrated in 2009 than prior to the alleged conspiracy.

PMID- 22971205
TI  - Randomized controlled trial of clinical pharmacy management of patients with type
      2 diabetes in an outpatient diabetes clinic in Jordan.
AB  - BACKGROUND: Glycemic goals (hemoglobin A1c < 7%) are often not achieved in
      patients with type 2 diabetes despite the availability of many effective
      treatments and the documented benefits of glycemic control in the reduction of
      long-term microvascular and macrovascular complications. Several studies have
      established the important positive effects of pharmacist-led management on
      achieving glycemic control and other clinical outcomes in patients with diabetes.
      Diabetes prevalence and mortality are increasing rapidly in Jordan. Nevertheless,
      clinical pharmacists in Jordan do not typically provide pharmaceutical care;
      instead, the principal responsibilities of pharmacists in Jordan are dispensing
      and marketing of medical products to physicians. OBJECTIVE: To assess the primary
      clinical outcome of glycemic control (A1c) and secondary outcomes, including
      blood pressure, lipid values, self-reported medication adherence, and self-care
      activities for patients with type 2 diabetes in an outpatient diabetes clinic
      randomly assigned to either usual care or a pharmacist-led pharmaceutical care
      intervention program. METHODS: Patients with type 2 diabetes attending an
      outpatient diabetes clinic of a large teaching hospital were recruited over a 4
      month period from January through April 2011 and randomly assigned to
      intervention and usual care groups using the Minim software technique. The
      intervention group at baseline received face-to-face objective-directed education
      from a clinical pharmacist about type 2 diabetes, prescription medications, and
      necessary lifestyle changes, followed by 8 weekly telephone follow-up calls to
      discuss and review the prescribed treatment plan and to resolve any patient
      concerns. The primary outcome measure was glycemic control (A1c), and secondary
      measures included systolic and diastolic blood pressure, complete lipid profile
      (i.e., total cholesterol, low-density lipoprotein cholesterol [LDL-C], high
      density lipoprotein cholesterol [HDL-C], serum triglycerides), and self-reported
      medication adherence (4-item Morisky Scale) and self-care activities (Summary of
      Diabetes Self-Care Activities questionnaire). Data were collected at baseline and
      at 6 months follow-up. Changes from baseline to follow-up were calculated for
      biomarker values, and between-group differences in the change amounts were tested
      using the t test for independent samples. A P value of < 0.05 was considered
      statistically significant. RESULTS: A total of 77 of 85 patients (90.6%) randomly
      assigned to the intervention group and 79 of 86 patients (91.9%) assigned to
      usual care had baseline and 6-month follow-up values. Compared with baseline
      values, patients in the intervention group had a mean reduction of 0.8% in A1c
      versus a mean increase of 0.1% from baseline in the usual care group (P = 0.019).
      The intervention group compared with the usual care group had small but
      statistically significant improvements in the secondary measures of fasting blood
      glucose, systolic and diastolic blood pressure, total cholesterol, LDL-C, serum
      triglycerides, self-reported medication adherence, and self-care activities.
      Between-group differences in changes in the secondary measures of HDL-C and body
      mass index were not significant. CONCLUSIONS: Patients with type 2 diabetes who
      received pharmacist-led pharmaceutical care in an outpatient diabetes clinic
      experienced reduction in A1c at 6 months compared with essentially no change in
      the usual care group. Six of 8 secondary biomarkers were improved in the
      intervention group compared with usual care.

PMID- 22971206
TI  - Dosing frequency and medication adherence in chronic disease.
AB  - BACKGROUND: Prior research has shown a decrease in medication adherence as dosing
      frequency increases; however, meta-analyses have not been able to demonstrate a
      significant inverse relationship between dosing frequency and adherence when
      comparing twice-daily versus once-daily dosing. OBJECTIVE: To determine the
      effect of scheduled dosing frequency on medication adherence in patients with
      chronic diseases. METHODS: A systematic literature search of Medline and Embase
      from January 1986 to December 2011 and a hand search of references were performed
      to identify eligible studies. Randomized and observational studies were included
      if they utilized a prospective design, assessed adult patients with chronic
      diseases, evaluated scheduled oral medications taken 1 to 4 times daily, and
      measured medication adherence for at least 1 month using an electronic monitoring
      device. Manual searches of reference sections of identified studies and
      systematic reviews were also performed to find other potentially relevant
      articles. Standard definitions for medication taking, regimen, and timing
      adherence were used and evaluated. Studies were pooled using a multivariate
      linear mixed-model method to conduct meta-regression accounting for both random
      and fixed effects, weighted by the inverse of the variance of medication
      adherence. RESULTS: Fifty-one studies, comprising 65, 76, and 47 dosing frequency
      arms for the taking, regimen, and timing adherence endpoints were included.
      Unadjusted adherence estimates were highest when the least stringent definition,
      taking adherence, was used (range for dosing frequencies: 80.1%-93.0%) and lowest
      when the most stringent definition, timing adherence, was used (range for dosing
      frequencies: 18.8%-76.9%). In multivariate meta-regression analyses, the adjusted
      weighted mean percentage adherence rates for all regimens dosed more frequently
      than once per day were significantly lower compared with once-daily regimens (for
      2-times, 3-times, and 4-times daily regimens, respectively: differences for
      taking adherence: -6.7%, -13.5%, and -19.2%; regimen adherence: -13.1%, -24.9%,
      and -23.1%; and timing adherence: -26.7%, -39.0%, and -54.2%). CONCLUSION:
      Patients with chronic diseases appear to be more adherent with once-daily
      compared with more frequently scheduled medication regimens. The use of more
      stringent definitions of adherence magnified these findings.

PMID- 22971207
TI  - Additive effect of tadalafil and simvastatin on monocrotaline-induced pulmonary
      hypertension rats.
AB  - OBJECTIVES: Tadalafil, an oral phosphodiesterase type-5 inhibitor, induces
      pulmonary vasorelaxation by inhibiting the breakdown of cyclic guanosine
      monophosphate whereas simvastatin, an oral 3-hydroxy-3-methylglutaryl (HMG)-CoA
      reductase inhibitor, has been shown to reverse pulmonary hypertension (PH) and
      attenuate vascular remodeling in animal models of pulmonary hypertension. We
      investigated whether the combination of tadalafil and simvastatin, which has
      different mechanisms of action, is superior to either drug alone in a rat model
      of monocrotaline-induced PH. METHODS: Male Sprague-Dawley rats were randomized to
      gavage with a vehicle, tadalafil (10 mg/kg/day), simvastatin (2 mg/kg/day), or
      tadalafi + simvastatin 21 days after the monocrotaline (60 mg/kg) injections. The
      hemodynamic and histological changes in the pulmonary arterioles, right heart
      hypertrophy, interleukin 6 (IL-6) levels and perivascular inflammation in the
      lungs were measured 35 days after monocrotaline exposure. RESULTS: The
      combination of tadalafil and simvastatin showed significantly more improvement in
      the mean pulmonary hypertension pressure (mPAP) and right ventricular hypertrophy
      compared with each monotherapy (p < 0.05). Combination therapy had additive
      effects on the increases in lung IL-6 levels and the perivascular inflammation
      score. CONCLUSIONS: These results suggest that the combination of tadalafil and
      simvastatin bears promise as an approach to treat PH, especially PH associated
      with inflammation.

PMID- 22971208
TI  - Inactivated Orf virus (Parapoxvirus ovis) elicits antifibrotic activity in models
      of liver fibrosis.
AB  - AIM: Inactivated Orf virus (ORFV, Parapoxvirus ovis) demonstrates strong
      antiviral activity in animal models including a human hepatitis B virus (HBV)
      transgenic mouse. In addition, expression of interferon (IFN)-gamma and
      interleukin-10 (IL-10) was induced after administration of inactivated ORFV in
      these mice. IFN-gamma and IL-10 are known to elicit antifibrotic activity. We
      therefore aimed to study antifibrotic activity of inactivated ORFV in models of
      liver fibrosis. METHODS: We characterized ORFV-induced hepatic cytokine
      expression in rats. We then studied ORFV in two models of liver fibrosis in rats,
      pig serum-induced liver fibrosis and carbon tetrachloride (CCL4 )-induced liver
      fibrosis. RESULTS: ORFV induced hepatic expression of IFN-gamma and IL-10 in
      rats. ORFV mediated antifibrotic activity when administrated concomitantly with
      the fibrosis-inducing agents in both models of liver fibrosis. Importantly, when
      CCL4 -induced liver fibrosis was already established, ORFV application still
      showed significant antifibrotic activity. In addition, we were able to
      demonstrate a direct antifibrotic effect of ORFV on stellate cells. CONCLUSION:
      These results establish a potential novel antifibrotic therapeutic approach that
      not only prevents but also resolves established liver fibrosis. Further studies
      are required to unravel the details of the mechanisms involved.

PMID- 22971210
TI  - Combination of electrochemistry and nuclear magnetic resonance spectroscopy for
      metabolism studies.
AB  - During the development of new materials demonstrating biological activity,
      prediction and identification of reactive intermediates generated in the course
      of drug metabolism in the human liver is of great importance. We present a rapid
      and purely instrumental method for the structure elucidation of possible phase I
      metabolites. With electrochemical (EC) conversion adopting the oxidative function
      of liver-inherent enzymes and nuclear magnetic resonance (NMR) spectroscopy
      enabling structure elucidation, comprehensive knowledge on potential metabolites
      can be gained. Paracetamol (APAP) has been known to induce hepatotoxicity when
      exceeding therapeutic doses and was therefore selected as the test compound. The
      reactive metabolite N-acetyl-p-benzoquinone imine has long been proven to be
      responsible for the toxic side effects of APAP and can easily be generated by EC.
      EC coupled online to NMR is a straightforward technique for structure elucidation
      of reactive drug intermediates at an early stage in drug discovery.

PMID- 22971211
TI  - Biofouling of reverse osmosis membranes used in river water purification for
      drinking purposes: analysis of microbial populations.
AB  - Biofouling in water treatment processes represents one of the most frequent
      causes of plant performance decline. Investigation of clogged membranes (reverse
      osmosis membranes, microfiltration membranes and ultrafiltration membranes) is
      generally performed on fresh membranes. In the present study, a multidisciplinary
      autopsy of a reverse osmosis membrane (ROM) was conducted. The membrane, which
      was used in sulfate-rich river water purification for drinking purposes, had
      become inoperative after 6 months because of biofouling and was later stored for
      18 months in dry conditions before analysis. SSU rRNA gene library construction,
      clone sequencing, T-RFLP, light microscope, and scanning electron microscope
      (SEM) observations were used to identify the microorganisms present on the
      membrane and possibly responsible for biofouling at the time of removal. The
      microorganisms were mainly represented by bacteria belonging to the phylum
      Actinobacteria and by a single protozoan species belonging to the Lobosea group.
      The microbiological analysis was interpreted in the context of the treatment
      plant operations to hypothesize as to the possible mechanisms used by
      microorganisms to enter the plant and colonize the ROM surface.

PMID- 22971212
TI  - Novel roles of Vmp1: inhibition metastasis and proliferation of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most deadly human cancers because of
      its high incidence of metastasis. Despite extensive efforts, therapies against
      metastasis of HCC remain underdeveloped. Vacuole membrane protein 1 (Vmp1) was
      recently identified to be involved in cancer-relevant processes; however, its
      expression, clinical significance and biological function in HCC progression are
      still unknown. Therefore, we evaluated the expression of Vmp1 in human HCC
      specimens. To functionally characterize Vmp1 in HCC, we upregulated its
      expression in HCCLM3 cells using a plasmid transfection approach, following which
      both in vitro and in vivo models were used to elucidate its role. A significant
      downregulation of Vmp1 was found in human HCC tissues and closely correlated with
      multiple tumor nodes, absence of capsular formation, vein invasion and poor
      prognosis of HCC. Such expression was verified with HCC cell lines including
      HepG2, MHCC97-L and HCCLM3, and the Vmp1 expression levels negatively correlated
      with metastatic potential. Interestingly, upregulation of Vmp1 significantly
      affects proliferation, migration, invasion and adhesion of HCCLM3 cells. Using a
      mouse model, we demonstrated that upregulation of Vmp1 was associated with
      suppression of growth and pulmonary metastases of HCC. Therefore, our data
      suggest Vmp1 is a novel prognostic marker and potential therapeutic target for
      metastasis of HCC.

PMID- 22971213
TI  - Excessive nicotinic acid increases methyl consumption and hydrogen peroxide
      generation in rats.
AB  - CONTEXT: Recent ecological evidence has showed a lag-correlation between the
      prevalence of diabetes and consumption of niacin (nicotinamide and nicotinic
      acid) in the US. Nicotinamide has been demonstrated to induce insulin resistance
      due to excess reactive oxygen species and methyl depletion, whereas the effect of
      nicotinic acid is poorly understood. OBJECTIVE: To examine the mechanism of the
      effect of nicotinic acid on glucose metabolism. MATERIALS AND METHODS: Rats were
      injected with different cumulative doses of nicotinic acid (0.5, 2, 4 g/kg) and
      nicotinamide (2 g/kg). A glucose tolerance test was given 2 h after the final
      injection. The role of methyl consumption and reactive oxygen species generation
      were evaluated by measuring N(1)-methylnicotinamide and hydrogen peroxide.
      RESULTS: Cumulative doses of nicotinic acid produced a dose-dependent increase in
      the plasma levels of N(1)-methylnicotinamide and hydrogen peroxide, which was
      associated with a decrease in liver and skeletal muscle glycogen levels. At the
      same dosage (2 g/kg), in comparison with nicotinamide, nicotinic acid was weaker
      in raising plasma N(1)-methylnicotinamide levels (0.7 +/- 0.11 ug/mL vs. 4.69 +/-
      0.24 ug/mL, P < 0.001), but stronger in increasing plasma hydrogen peroxide
      levels (1.88 +/- 0.07 umol/L vs. 1.55 +/- 0.05 umol/L, P < 0.001). Moreover,
      nicotinamide, unlike nicotinic acid, did not reduce liver glycogen levels.
      DISCUSSION AND CONCLUSION: This study suggested that excessive nicotinic acid,
      like nicotinamide, might induce methyl consumption, oxidative stress and insulin
      resistance. Long-term consumption high niacin may increase the risk of type 2
      diabetes.

PMID- 22971214
TI  - Ovarian structure and oogenesis of catfish Pimelodella vittata (Lutken, 1874)
      (Siluriformes, Heptapteridae).
AB  - The morphology of the ovaries and oogenesis of Pimelodella vittata were studied
      using anatomical and histological techniques to provide information of its
      reproductive biology. Eighty adult females were captured trimonthly during the
      period November 2005 to October 2006. The ovaries are paired, saculiform organs,
      which are coated with tunica albuginea and contain ovigerous lamellae, where the
      oocytes develop before being released into the ovarian lumen and following the
      ovarian duct until reaching the genital papilla. Oogenesis was divided into
      stages based on the alterations to the nucleus, ooplasm and surrounding
      follicular layers. Oogonia form groups from the germinal epithelium have
      asynchronous development and differentiate into initial perinucleolar oocytes.
      The formation of the zona pellucida is initiated in the advanced perinucleolar
      oocytes reaching a thickness of 1.46+/-0.58 MUm in the vitellogenic oocytes. The
      follicular cells are squamous in perinucleolar oocytes, become cubical in the pre
      vitellogenic oocytes and prismatic in the vitellogenic oocytes with a height of
      11.20+/-4.74 MUm. The histochemical reactions indicate that zona pellucida,
      cortical alveoli and yolk globules contain neutral glycoproteins and the
      follicular cells contain neutral glycoproteins in association with carboxylated
      and sulphated glycoconjugates. Statistical analyses showed significant
      differences in the diameter of the oocytes and follicular cells height as oocytes
      matured. This study represents the first data about the ovarian structure and
      oogenesis of this species.

PMID- 22971215
TI  - Treatment with lenalidomide in myelodysplastic syndromes with deletion 5q:
      results from the Dutch named patient program.

PMID- 22971217
TI  - Sample preparation and image acquisition using optical-reflective microscopy in
      the measurement of fiber orientation in thermoplastic composites.
AB  - A complete sample preparation procedure used to determine three-dimensional fiber
      orientation from optical micrographs of glass fiber-reinforced thermoplastic
      composites is presented. Considerations for elimination of irregularities in the
      elliptical footprints, contrast enhancement between fibers and surrounding
      polymer matrix, controlled-etching that allows the identification of small
      shadows where fiber recedes into the matrix, and topographical reconstruction of
      the elliptical footprint are described in the procedure. This procedure has
      produced high-quality optical micrographs employed to obtain accurate fiber
      orientation data for thermoplastic composites using the method of ellipses. The
      optimal definition of the nonelliptical footprints' borders allows an accurate
      measurement of orientation in small sampling areas.

PMID- 22971216
TI  - Evaluation of co-oximetry for the measurement of methemoglobin in rainbow trout
      (Oncorhynchus mykiss) and values in 3 salmonid species.
AB  - BACKGROUND: Methemoglobin (metHb) is oxidized hemoglobin that cannot reversibly
      bind oxygen, and concentrations in healthy fish have been reported to be 0.6
      24.8% compared with 0-3% in healthy mammals. In fish, metHb has been measured
      using spectrophotometric methods using potassium cyanide (KCN), but not using co
      oximetry, which is the preferred method for human samples. OBJECTIVES: The aims
      of this study were to evaluate co-oximetry as a method for measuring metHb in
      Oncorhynchus mykiss, compare co-oximetry with a KCN spectrophotometric method,
      and establish reference values for metHb concentrations as measured using co
      oximetry in O mykiss, Salmo salar, and Salvelinus fontinalis. METHODS: Blood
      samples from healthy female O mykiss, female S salar, and female and male S
      fontinalis were prepared by separation and washing of erythrocytes in
      Tris/NaCl/EDTA buffer followed by lysis in Tris/EDTA buffer. MetHb concentrations
      were measured using an IL-682 co-oximeter. Moderate and high metHb concentrations
      were produced in vitro using NaNO(2). RESULTS: At low concentrations of
      methemoglobin, CVs for intraday precision were 10.3% and 53.9% using co-oximetry
      and the KCN spectrophotometric method, respectively. The CV for interday
      precision using co-oximetry was 11.9%. MetHb concentrations were stable in whole
      blood stored at 4 degrees C for 7 days. MetHb concentrations were linear up to
      58.2% (r = .99) using co-oximetry and 27.5% (r = .94) using the KCN method. The
      lower limit of detection for metHb was 0.02 g/dL using co-oximetry. Reference
      values for metHb concentrations using co-oximetry in O mykiss, S salar, and S
      fontinalis (n = 40 of each species) were 0.6-1.8%, 1.1-1.9%, and 1.1-4.0%,
      respectively. CONCLUSIONS: Co-oximetry can be used to measure methemoglobin in
      blood from fish, in particular in O mykiss, and is better than the KCN
      spectrophotometric method. Reference values for methemoglobin concentrations in O
      mykiss, S salar, and S fontinalis are similar to those in mammals.

PMID- 22971218
TI  - Using c-Fos/c-Jun as hetero-dimer interaction model to optimize donor to acceptor
      concentration ratio range for three-filter fluorescence resonance energy transfer
      (FRET) measurement.
AB  - Sensitized emission FRET detection method based on three-filter fluorescence
      microscopy is widely used and more suitable for live cell FRET imaging and
      dynamic protein-protein interaction analysis. But when it is applied to detect
      two proteins interaction in living cells, this intensity-based detection method
      is complicated by many experimental factors such as spectral crosstalk and
      spectral bleed-through and variable donor to acceptor concentration ratio. There
      are several FRET algorithms developed recently to correct those factors in order
      to quantitatively gauge and compare FRET signals between different experimental
      groups. But the algorithms are often difficult to choose when they are applied to
      certain experiments. In this research, we use c-Fos/c-Jun as a simple hetero
      dimer interaction model to quantitatively detect and compare the FRET signals
      based on the following widely used sensitized emission FRET algorithms: N(FRET) ,
      FRET(N) , FR, FRET(R) , E(app)  and E(EFF) . We optimized the donor to acceptor
      concentration ratio range for the above FRET algorithms and facilitate their use
      in accurate FRET signal determination based on the three-filter FRET microscopy.

PMID- 22971219
TI  - Generalization of the polar representation in time domain fluorescence lifetime
      imaging microscopy for biological applications: practical implementation.
AB  - The polar representation or phasor, which provides a fast and visual indication
      on the number of exponentials present in the intensity decay of the fluorescence
      lifetime images is increasingly used in time domain fluorescence lifetime imaging
      microscopy experiments. The calculations of the polar coordinates in time domain
      fluorescence lifetime imaging microscopy experiments involve several experimental
      parameters (e.g. instrumental response function, background, angular frequency,
      number of temporal channels) whose role has not been exhaustively investigated.
      Here, we study theoretically, computationally and experimentally the influence of
      each parameter on the polar calculations and suggest parameter optimization for
      minimizing errors. We identify several sources of mistakes that may occur in the
      calculations of the polar coordinates and propose adapted corrections to
      compensate for them. For instance, we demonstrate that the numerical integration
      method employed for integrals calculations may induce errors when the number of
      temporal channels is low. We report theoretical generalized expressions to
      compensate for these deviations and conserve the semicircle integrity,
      facilitating the comparison between fluorescence lifetime imaging microscopy
      images acquired with distinct channels number. These theoretical generalized
      expressions were finally corroborated with both Monte Carlo simulations and
      experiments.

PMID- 22971220
TI  - Red-shifted fluorescent proteins monitor enzymatic activity in live HT-1080 cells
      with fluorescence lifetime imaging microscopy (FLIM).
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is a membrane-tethered
      collagenase primarily involved in the mechanical destruction of extracellular
      matrix proteins. MT1-MMP has also been shown to be upregulated in several types
      of cancers. Many coordinated functions of MT1-MMP during migration and invasion
      remain to be determined. In this paper, live cells from the invasive cell line HT
      1080 were imaged using an intracellular Forster resonance energy transfer-based
      biosensor specific for MT1-MMP; a substrate specific for MT1-MMP was hybridized
      with the mOrange2 and mCherry fluorescent proteins to form the Forster resonance
      energy transfer-based sensor. The configuration of the biosensor was determined
      with fluorescence lifetime-resolved imaging microscopy using both a polar plot
      based analysis and a rapid data acquisition modality of fluorescence lifetime
      resolved imaging microscopy known as phase suppression. Both configurations of
      the biosensor (with or without cleavage by MT1-MMP) were clearly resolvable in
      the same cell. Changes in the configuration of the MT1-MMP biosensor were
      observed primarily along the edge of the cell following the removal of the MMP
      inhibitor GM6001. The intensities highlighted by phase suppression correlated
      well with the fractional intensities derived from the polar plot.

PMID- 22971221
TI  - N-chlorotaurine and its analogues N,N-dichloro-2,2-dimethyltaurine and N
      monochloro-2,2-dimethyltaurine are safe and effective bactericidal agents in ex
      vivo corneal infection models.
AB  - PURPOSE: N-chlorotaurine (NCT) and its analogues N-monochloro-2,2-dimethyltaurine
      (NVC-612) and N-dichloro-2,2-dimethyltaurine (NVC-422) are new anti-infectives
      for topical treatment for conjunctivitis. The aim of this study was to show that
      these compounds are safe in an EpiOcular model and effective in corneas infected
      ex vivo. METHODS: Corneal buttons were excised from porcine eyes. In 183 of the
      229 corneas, erosion and artificial superficial stromal incision were induced.
      They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus
      aureus for 24 hr at 37 degrees C and incubated in solutions of the test
      substances at 37 degrees C and pH 7.1. Subsequently, they were subjected to
      histology (n = 20) or homogenized followed by quantitative bacterial cultures (n
      = 209). Ocular irritation was tested using the EpiOcularTM tissue system (MatTek
      Corporation). RESULTS: Bacterial accumulations were detected histologically both
      on the corneal surface and also in the anterior third of the stroma of incised
      corneal buttons. All three test compounds at a concentration of 55 mm (equals 1%
      NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately
      5 log10 after 60- and 120-min incubation, respectively. Significant killing was
      observed as early as after 5-min incubation. Also intrastromal bacteria were
      inactivated. In the EpiOcularTM tissue model, NCT, NVC-422 and NVC-612 had no or
      very low potential to irritate corneal tissue. CONCLUSION: N-chlorotaurine, NVC
      422 and NVC-612 are non-irritating in cornea and kill P. aeruginosa and S.
      aureus, even following penetration into the deeper corneal stromal layers.

PMID- 22971222
TI  - Emerging role of nanocarriers to increase the solubility and bioavailability of
      curcumin.
AB  - INTRODUCTION: Curcumin is a safe, affordable and natural bioactive molecule of
      turmeric (Curcuma longa). It has gained considerable attention in recent years
      for its multiple pharmacological activities. However, its optimum pharmaceutical
      potential has been limited by its lack of aqueous solubility and poor
      bioavailability. To mitigate the above limitations, recently various
      nanostructured water-soluble delivery systems were developed to increase the
      solubility and bioavailability of curcumin. AREAS COVERED: Major reasons
      contributing to the low bioavailability of curcumin appear to be owing to its
      poor solubility, low absorption, rapid metabolism and rapid systemic elimination.
      The present review summarizes the strategies using curcumin in various
      nanocarrier delivery systems to overcome poor solubility and inconsistent
      bioavailability of curcumin and describes the current status and challenges for
      the future. EXPERT OPINION: The development of various drug delivery systems to
      deliver curcumin will certainly provide a step up towards augmenting the
      therapeutic activity of curcumin thereby increasing the solubility and
      bioavailability of curcumin. However, the future of such delivery technology will
      be highly dependent on the development of safe, non-toxic and non-immunogenic
      nanocarriers.

PMID- 22971224
TI  - Overcoming low orbital overlap and triplet instability problems in TDDFT.
AB  - Low orbital overlap and triplet instability problems in time-dependent density
      functional theory (TDDFT) are investigated for a new benchmark set, encompassing
      challenging singlet and triplet excitation energies of local, charge-transfer,
      and Rydberg character. The low orbital overlap problem is largely overcome for
      both singlet and triplet states by the use of a Coulomb-attenuated functional.
      For all the categories of functional considered, however, errors associated with
      triplet instability problems plague high overlap excitations, as exemplified by
      the excited states of acenes and polyacetylene oligomers. Application of the Tamm
      Dancoff approximation reduces these errors for both singlet and triplet states,
      while leaving low-overlap excitations unaffected. The study illustrates the
      synergy between overlap and stability and highlights the success of a combined,
      Coulomb-attenuated Tamm-Dancoff approach.

PMID- 22971223
TI  - Remission of screen-detected metabolic syndrome and its determinants: an
      observational study.
AB  - BACKGROUND: Early detection and treatment of the metabolic syndrome may prevent
      diabetes and cardiovascular disease. Our aim was to assess remission of the
      metabolic syndrome and its determinants after a population based screening
      without predefined intervention in the Netherlands. METHODS: In 2006 we detected
      406 metabolic syndrome cases (The National Cholesterol Education Program's Adult
      Treatment Panel III (NCEP ATP III) definition) among apparently healthy
      individuals with an increased waist circumference. They received usual care in a
      primary care setting. After three years metabolic syndrome status was re
      measured. We evaluated which baseline determinants were independently associated
      with remission. RESULTS: The remission rate among the 194 participants was 53%.
      Baseline determinants independently associated with a remission were the presence
      of more than three metabolic syndrome components (OR 0.46) and higher levels of
      waist circumference (OR 0.91), blood pressure (OR 0.98) and fasting glucose (OR
      0.60). CONCLUSIONS: In a population with screen-detected metabolic syndrome
      receiving usual care, more than half of the participants achieved a remission
      after three years. This positive result after a relatively simple strategy
      provides a solid basis for a nation-wide implementation. Not so much socio
      demographic variables but a higher number and level of the metabolic syndrome
      components were predictors of a lower chance of remission. In such cases, primary
      care physicians should be extra alert.

PMID- 22971225
TI  - SOP: corpus cavernosum assessment (cavernosography/cavernosometry).
AB  - INTRODUCTION: There is no universal gold standard diagnostic test to
      differentiate psychogenic from organic erectile dysfunction (ED).
      Cavernosography/cavernosometry has been used to evaluate veno-occlusive
      dysfunction (VOD) in men with a proposed organic ED. AIM: To develop evidence
      based guidelines for the performance and interpretation of
      cavernosography/cavernosometry. METHODS: Review the methodology behind
      cavernosography/cavernosometry and evaluate the evidence that supports its use
      and interpretation of results. MAIN OUTCOME MEASURE: Expert opinion based on
      review of the literature, extensive internal committee discussion, public
      presentation, and debate. RESULTS: The detailed technique of
      cavernosography/cavernosometry is described. An evidence-based perspective to the
      use and interpretation of cavernosometry is presented. CONCLUSION: The positive
      predictive value of cavernosometry still needs further assessment. It is unknown
      how many potent men would test positive for VOD (false positive).

PMID- 22971226
TI  - Available hemostatic measures for postpartum hemorrhage in rural   settings.

PMID- 22971229
TI  - Advances in neurology 2011-12.

PMID- 22971231
TI  - Ex-vacuo interna phenomenon.

PMID- 22971228
TI  - Early therapy interpersonal process differentiating clients high and low in
      outcome expectations.
AB  - The present study compared early interpersonal process, during resistant and
      cooperative segments of session 1, between clients who went on to have low (n=9)
      versus high (n=8) treatment outcome expectations. Baseline outcome expectations
      were assessed prior to any therapist contact. During resistance episodes, there
      was substantially less affiliative reciprocity (i.e., complementarity), and
      greater client separation and hostility in the low versus high expectations
      group. During cooperation episodes, therapists of low versus high outcome
      expectation clients engaged in lower levels of affirming and understanding, and
      higher levels of control. These findings suggest a potentially potent association
      between in-session interpersonal process and early client outcome expectations.

PMID- 22971232
TI  - Charcot-Marie-Tooth hereditary neuropathy due to a mitochondrial ATP6 mutation.

PMID- 22971227
TI  - Characterization of a cobalt-specific P(1B)-ATPase.
AB  - The P(1B)-type ATPases are a ubiquitous family of P-type ATPases involved in the
      transport of transition metal ions. Divided into subclasses based on sequence
      characteristics and substrate specificity, these integral membrane transporters
      play key roles in metal homeostasis, metal tolerance, and the biosynthesis of
      metalloproteins. The P(1B-4)-ATPases have the simplest architecture of the five
      P(1B)-ATPase families and have been suggested to play a role in Co(2+) transport.
      A P(1B-4)-ATPase from Sulfitobacter sp. NAS-14.1, designated sCoaT, has been
      cloned, expressed, and purified. Activity assays indicate that sCoaT is specific
      for Co(2+). A single Co(2+) binding site is present, and optical, electron
      paramagnetic resonance, and X-ray absorption spectroscopic data are consistent
      with tetrahedral coordination by oxygen and nitrogen ligands, including a
      histidine and likely a water. Surprisingly, there is no evidence for coordination
      by sulfur. Mutation of a conserved cysteine residue, Cys 327, in the signature
      transmembrane Ser-Pro-Cys metal binding motif does not abolish the ATP hydrolysis
      activity or affect the spectroscopic analysis, establishing that this residue is
      not involved in the initial Co(2+) binding by sCoaT. In contrast, replacements of
      conserved transmembrane residues Ser 325, His 657, Glu 658, and Thr 661 with
      alanine abolish ATP hydrolysis activity and Co(2+) binding, indicating that these
      residues are necessary for Co(2+) transport. These data represent the first in
      vitro characterization of a P(1B-4)-ATPase and its Co(2+) binding site.

PMID- 22971233
TI  - Concomitant myotonic dystrophy type 1, CIDP-like neuropathy and Hashimoto
      thyroiditis: a causal link?

PMID- 22971235
TI  - Improved methods for axenic culture of Labyrinthula terrestris, causal agent of
      rapid blight of turfgrasses.
AB  - The genus  Labyrinthula  is a group of unicellular microorganisms with spindle
      shaped cells that move in an ectoplasmic network. Most Labyrinthula species are
      saprotrophic and found in coastal marine or estuarine habitats; however,
      exceptions exist, such as  Labyrinthula terrestris , a terrestrial plant pathogen
      that causes rapid blight on cool-season turfgrasses. Labyrinthula spp. can be
      grown in culture, which facilitates studies on their biology and pathology.
      However, axenic culture of L. terrestris has always been challenging. We modified
      the most commonly used Labyrinthula growth medium, serum seawater agar (SSA), and
      designed 2 media for improved pure culture, modified SSA (MSSA) and grass extract
      SSA (GESSA). A comparative assessment of these 2 media and basic SSA was made to
      measure the growth responses of 18 L. terrestris isolates. Results indicate that
      the average colony area was greatest on GESSA followed by MSSA, while cultures
      lived longest on MSSA followed by GESSA. We also suggest an improved long-term
      culture technique to maintain viable L. terrestris isolates for at least 2 years.

PMID- 22971234
TI  - Anomalous size-dependent decay of low-energy luminescence from PbS quantum dots
      in colloidal solution.
AB  - We report on an anomalous size dependence of the room-temperature
      photoluminescence decay time from the lowest-energy state of PbS quantum dots in
      colloidal solution, which was found using the transient luminescence
      spectroscopy. The observed 10-fold reduction in the decay time (from ~2.5 to 0.25
      MUs) with the increase in the quantum dots' diameter is explained by the
      existence of phonon-induced transitions between the in-gap state-whose energy
      drastically depends on the diameter-and the fundamental state of the quantum
      dots.

PMID- 22971237
TI  - Plants and plant products with potential antipsoriatic activity--a review.
AB  - CONTEXT: Psoriasis vulgaris is a hyper proliferative, autoimmune skin disorder
      affecting 1-3% of the world's population. The prescribed synthetic drugs for the
      treatment of psoriasis are associated with severe side effects, thus, researchers
      around the globe are searching for new, effective, and safer drugs from natural
      resources. OBJECTIVE: The present review has been prepared with an objective to
      compile exhaustive literature on pharmacological reports on antipsoriatic plants,
      plant products, and formulations. An attempt has been made to incorporate
      chemical constituents (with structures) isolated from different plants
      responsible for antipsoriatic activity and their possible mechanism of actions in
      this review. MATERIALS AND METHODS: The review has been compiled using references
      from major databases like Chemical Abstracts, Medicinal and Aromatic Plants
      Abstracts, PubMed, Scirus, Google scholar, Open J Gate, Scopus, Science Direct
      and Online Journals, and includes 127 references. RESULTS: A survey of literature
      revealed that extracts/fractions/isolates from 18 plants, 23 chemical
      constituents of plant origin and 40 plant-based formulations from various systems
      of medicine have been reported to possess antipsoriatic activity, and 37
      antipsoriatic formulations containing plants have been patented. CONCLUSION:
      Preliminary antipsoriatic activity studies have been carried out on crude
      extracts of traditionally used and medicinally promising plants. Such plants need
      to be explored properly with a view to isolate antipsoriatic constituents, and to
      evaluate their possible mode of actions so that these plant drugs could be
      exploited properly as potential antipsoriatic drugs.

PMID- 22971236
TI  - Mass spectrometry analysis of human P2X1 receptors; insight into phosphorylation,
      modelling and conformational changes.
AB  - Recombinant FlagHis(6)  tagged Human P2X1 receptors expressed in HEK293 cells
      were purified, digested with trypsin and analysed by mass spectroscopy (96%
      coverage following de-glycosylation and reduction). The receptor was basally
      phosphorylated at residues S387, S388 and T389 in the carboxyl terminus, a triple
      alanine mutant of these residues had a modest ~ 25% increase in current amplitude
      and recovery from desensitization. Chemical modification showed that
      intracellular lysine residues close to the transmembrane domains and the membrane
      stabilization motif are accessible to the aqueous environment. The membrane
      impermeant cross-linking reagent 3,3'-Dithiobis (sulfosuccinimidylpropionate)
      (DTSSP) reduced agonist binding and P2X1 receptor currents by > 90%, and modified
      lysine residues were identified by mass spectroscopy. Mutation to remove reactive
      lysine residues around the ATP-binding pocket had no effect on inhibtion of
      agonist evoked currents following DTSSP. However, agonist evoked currents were ~
      10-fold higher than for wild type following DTSSP treatment for mutants K199R,
      K221R and K199R-K221R. These mutations remove reactive residues distant from the
      agonist binding pocket that are close enough to cross-link adjacent subunits.
      These results suggest that conformational change in the P2X1 receptor is required
      for co-ordination of ATP action.

PMID- 22971238
TI  - The Collaborative Assessment and Management of Suicidality (CAMS): an evolving
      evidence-based clinical approach to suicidal risk.
AB  - The Collaborative Assessment and Management of Suicidality (CAMS) is an evidence
      based clinical intervention that has significantly evolved over 25 years of
      clinical research. CAMS is best understood as a therapeutic framework that
      emphasizes a unique collaborative assessment and treatment planning process
      between the suicidal patient and clinician. This process is designed to enhance
      the therapeutic alliance and increase treatment motivation in the suicidal
      patient. Central to the CAMS approach is the use of the Suicide Status Form
      (SSF), which is a multipurpose clinical assessment, treatment planning, tracking,
      and outcome tool. The original development of CAMS was largely rooted in SSF
      based quantitative and qualitative assessment of suicidal risk. As this line of
      research progressed, CAMS emerged as a problem-focused clinical intervention that
      is designed to target and treat suicidal "drivers" and ultimately eliminate
      suicidal coping. To date, CAMS (and the clinical use of the SSF) has been
      supported by six published correlational studies and one randomized clinical
      trial (RCT). Currently, two well-powered RCTs are under way, and various new CAMS
      related projects are also being pursued. The clinical and empirical evolution of
      CAMS-how it was developed and what are the next steps for this clinical approach
      are described here.

PMID- 22971239
TI  - Frequency and distribution of lymphoma types in a tertiary care hospital in South
      India: analysis of 5115 cases using the World Health Organization 2008
      classification and comparison with world literature.
AB  - This study aimed to analyze the distribution of lymphoid neoplasms in a single
      tertiary care center in India using the World Health Organization (WHO) 2008
      classification. Histological material of 5115 patients with histopathological
      diagnosis of lymphoma, diagnosed over a period of 10 years (2001-2010), was
      analyzed retrospectively. Hodgkin lymphoma (HL) constituted 21.3% (n = 1089) and
      non-Hodgkin lymphomas (NHLs) constituted 78.7% (n = 4026). Of these, B-cell
      neoplasms accounted for 78.6% (n = 3166) and T-cell/natural killer (NK)-cell
      neoplasms 20.2% (n = 815) of the NHLs. The commonest subtype of NHL was diffuse
      large B-cell lymphoma (n = 1886, 46.9%). The frequency of peripheral T-cell/NK
      cell lymphomas in this study was higher than in the Western literature but less
      than the frequency documented in some Asian countries. Similar to the Western
      literature but in contrast to previous Indian studies, peripheral T-cell
      lymphoma, not otherwise specified (PTCL NOS) (n = 238) was the commonest
      histological subtype of T-cell/NK-cell NHL in this study and constituted 5.9% of
      the total NHLs. Mixed cellularity (MC-CHL) (n = 488, 45%) was the major subtype
      of HL. Primary extranodal lymphoma (ENL) accounted for 32.8% (n = 1321) of all
      NHLs and most frequently involved the gastrointestinal tract. This study also
      documents the frequency of many rare types of lymphoma in South India.

PMID- 22971240
TI  - Whole transcriptome analyses of six thoroughbred horses before and after exercise
      using RNA-Seq.
AB  - BACKGROUND: Thoroughbred horses are the most expensive domestic animals, and
      their running ability and knowledge about their muscle-related diseases are
      important in animal genetics. While the horse reference genome is available,
      there has been no large-scale functional annotation of the genome using expressed
      genes derived from transcriptomes. RESULTS: We present a large-scale analysis of
      whole transcriptome data. We sequenced the whole mRNA from the blood and muscle
      tissues of six thoroughbred horses before and after exercise. By comparing
      current genome annotations, we identified 32,361 unigene clusters spanning 51.83
      Mb that contained 11,933 (36.87%) annotated genes. More than 60% (20,428) of the
      unigene clusters did not match any current equine gene model. We also identified
      189,973 single nucleotide variations (SNVs) from the sequences aligned against
      the horse reference genome. Most SNVs (171,558 SNVs; 90.31%) were novel when
      compared with over 1.1 million equine SNPs from two SNP databases. Using
      differential expression analysis, we further identified a number of exercise
      regulated genes: 62 up-regulated and 80 down-regulated genes in the blood, and
      878 up-regulated and 285 down-regulated genes in the muscle. Six of 28 previously
      known exercise-related genes were over-expressed in the muscle after exercise.
      Among the differentially expressed genes, there were 91 transcription factor
      encoding genes, which included 56 functionally unknown transcription factor
      candidates that are probably associated with an early regulatory exercise
      mechanism. In addition, we found interesting RNA expression patterns where
      different alternative splicing forms of the same gene showed reversed expressions
      before and after exercising. CONCLUSION: The first sequencing-based horse
      transcriptome data, extensive analyses results, deferentially expressed genes
      before and after exercise, and candidate genes that are related to the exercise
      are provided in this study.

PMID- 22971241
TI  - Coupling methanol denaturation, immobilized trypsin digestion, and accurate mass
      and time tagging for liquid-chromatography-based shotgun proteomics of low
      nanogram amounts of RAW 264.7 cell lysate.
AB  - We report the shotgun proteomic analysis of mammalian cell lysates that contain
      low nanogram amounts of protein. Proteins were denatured using methanol, digested
      using immobilized trypsin, and analyzed by UPLC-ESI-MS/MS. The approach generated
      more peptides and higher sequence coverage for a mixture of three standard
      proteins than the use of free trypsin solution digestion of heat- or urea
      denatured proteins. We prepared triplicate RAW 264.7 cell lysates that contained
      6, 30, 120, and 300 ng of protein. An average of 2 +/- 1, 23 +/- 2, 134 +/- 11,
      and 218 +/- 26 proteins were detected for each sample size, respectively. The
      numbers of both protein and peptide IDs scaled linearly with the amount of sample
      taken for analysis. Our approach also outperformed traditional methods (free
      trypsin digestion of heat- or urea-denatured proteins) for 6-300 ng RAW 264.7
      cell protein analysis in terms of number of peptides and proteins identified. The
      use of accurate mass and time (AMT) tags resulted in the identification of an
      additional 16 proteins based on 20 peptides from the 6 ng cell lysate prepared
      with our approach. When AMT analysis was performed for the 6 ng cell lysate
      prepared with traditional methods, no reasonable peptide signal could be
      obtained. In all cases, roughly ~30% of the digested sample was taken for
      analysis, corresponding to the analysis of a 2 ng aliquot of homogenate from the
      6 ng cell lysate.

PMID- 22971242
TI  - Drug safety evaluation of dronedarone in atrial fibrillation.
AB  - INTRODUCTION: Dronedarone was developed with the intent of replicating the
      antiarrhythmic effects of amiodarone, while minimizing its side effects. AREAS
      COVERED: Side effects reported in eight randomized clinical trials are discussed,
      comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA,
      ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or
      dronedarone and amiodarone (DIONYSOS, total number of patients treated with
      dronedarone 249). EXPERT OPINION: The results of the first trials, including
      ATHENA, set high expectations by suggesting that dronedarone may decrease the
      risk of hospitalization (and even cardiovascular mortality) among patients with
      paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded
      as an easy-to-use drug that could be prescribed by general practitioners;
      unfortunately, dronedarone has not met these expectations. Dronedarone may
      increase mortality and heart failure hospitalization in patients with advanced
      NYHA class and in patients with permanent AF, preventing its use in these
      settings. In addition to gastrointestinal side effects that may lead to
      discontinuation in 5 - 10% of patients, dronedarone may induce very rare but
      severe liver and lung toxicity. Despite these limitations and its relatively
      limited antiarrhythmic potency, dronedarone may still be a useful drug for well
      selected patients.

PMID- 22971243
TI  - The vertical hip fracture - a treatment challenge. A cohort study with an up to 9
      year follow-up of 137 consecutive hips treated with sliding hip screw and
      antirotation screw.
AB  - BACKGROUND: Femoral neck fractures with a vertical orientation have been
      associated with an increased risk for failure as they are both axial and
      rotational unstable and experience increased shear forces compared to the
      conventional and more horizontally oriented femoral neck fractures. The purpose
      of this study was to analyse outcome and risk factors for reoperation of these
      uncommon fractures. METHODS: A cohort study with a consecutive series of 137 hips
      suffering from a vertical hip fracture, treated with one method: a sliding hips
      screw with plate and an antirotation screw. Median follow-up time was 4.8 years.
      Reoperation data was validated against the National Board of Health and Welfare's
      national registry using the unique Swedish personal identification number.
      RESULTS: The total reoperation rate was 18%. After multivariable Logistic
      regression analysis adjusting for possible confounding factors there was an
      increased risk for reoperation for displaced fractures (22%) compared to
      undisplaced fractures (3%), and for fractures with poor implant position (38%)
      compared to fractures with adequate implant position (15%). CONCLUSIONS: The
      reoperation rate was high, and special attention should be given to achieve an
      appropriate position of the implant.

PMID- 22971244
TI  - Aurora kinase B is a potential therapeutic target in pediatric diffuse intrinsic
      pontine glioma.
AB  - Pediatric high-grade astrocytomas (HGAs) account for 15-20% of all pediatric
      central nervous system tumors. These neoplasms predominantly involve the
      supratentorial hemispheres or the pons--diffuse intrinsic pontine gliomas (DIPG).
      Assumptions that pediatric HGAs are biologically similar to adult HGAs have
      recently been challenged, and the development of effective therapeutic modalities
      for DIPG and supratentorial HGA hinges on a better understanding of their
      biological properties. Here, 20 pediatric HGAs (9 DIPGs and 11 supratentorial
      HGAs) were subject to gene expression profiling following approval by the
      research ethics board at our institution. Many of these tumors showed expression
      signatures composed of genes that promote G1/S and G2/M cell cycle progression.
      In particular, Aurora kinase B (AURKB) was consistently and highly overexpressed
      in 6/9 DIPGs and 8/11 HGAs. Array data were validated using quantitative real
      time PCR and immunohistochemistry, as well as cross-validation of our data set
      with previously published series. Inhibition of Aurora B activity in DIPG and in
      pediatric HGA cell lines resulted in growth arrest accompanied by morphological
      changes, cell cycle aberrations, nuclear fractionation and polyploidy as well as
      a reduction in colony formation. Our data highlight Aurora B as a potential
      therapeutic target in DIPG.

PMID- 22971245
TI  - Rational design of DNA vaccines for the induction of human papillomavirus type 16
      E6- and E7-specific cytotoxic T-cell responses.
AB  - Many DNA vaccine candidates have been developed for the treatment of human
      papillomavirus type 16 (HPV16)-induced malignancies. Most of these vaccines
      consist of a fusion of E7 with a "carrier-protein" that functions to increase the
      potency of the vaccine. The nature of these carrier-proteins varies widely, and
      the mechanisms proposed to explain the enhanced immunogenicity of such fusions
      are often linked to the biological function of the carrier-protein. However, the
      potentiating effect of these carrier-proteins might also be explained by more
      general mechanisms, such as the provision of CD4+ T-cell help, increased antigen
      stability, or altered subcellular localization of the antigen. To assess whether
      these more generic mechanisms could suffice to generate highly immunogenic DNA
      vaccines, we evaluated a series of modular HPV16 E7 DNA vaccines in which the
      presence of CD4+ T-cell help, the presence of an endogenous carrier-protein, and
      the subcellular localization of the antigen could be systematically altered.
      Using this approach, we demonstrate that the addition of an element that provides
      CD4+ T-cell help, elements that enforce endoplasmic reticulum (ER)
      localization/retention are both necessary and sufficient to create markedly
      effective HPV16 E7-directed DNA vaccines. Importantly, the resulting design rules
      also apply to an HPV16 E6-directed DNA vaccine. The developed "HELP(ER)" HPV DNA
      vaccines encode only very limited additional sequences besides the antigen,
      thereby reducing the risk of antigenic competition and/or autoimmunity.

PMID- 22971246
TI  - Scalar relaxation of the second kind: a potential source of information on the
      dynamics of molecular movements. 1. Investigation of solution reorientation of N
      methylpyridone and 1,3-dimethyluracil using measurements of longitudinal
      relaxation rates in the rotating frame.
AB  - The practical utility of the method of retrieving the relaxation rate of a
      quadrupole nucleus via the scalar relaxation of the second kind (SC2) of an I =
      1/2 spin nucleus has been considered once again. The study was motivated by the
      fact that such data are frequently very useful in investigations of
      reorientational movements of molecules in solutions. At the same time, the
      parameters describing spin-spin and quadrupolar couplings, necessary in such
      studies, have become relatively easily accessible owing to a remarkable progress
      in theoretical methods. It was shown that even in the case of small N-C coupling
      constants ((1)J = 7-8 Hz) the classical method of approaching SC2 relaxation
      effects by measurements of the longitudinal relaxation rates in the rotating
      frame, although somewhat tedious, can yield acceptably accurate results. The
      whole procedure has been successfully applied in the investigation of molecular
      movements of N-methylpyridone (1) and 1,3-dimethyluracil (2) in acetone solution.

PMID- 22971247
TI  - Modifying risk factors to prevent and treat erectile dysfunction.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common complaint in men over 40
      years of age and prevalence rates increase with age. Comorbidities such as heart
      disease, diabetes, dyslipidemia, hypertension, and depression have been described
      as primary risk factors for the development of ED. Additionally, a number of
      modifiable lifestyle factors, including physical activity, smoking, alcohol
      consumption, diabetes control, and obesity, have been associated with ED. AIM:
      The association of modifiable behavioral factors with ED, mainly among men
      without recognized comorbidities, opens the possibility for intervention
      strategies to prevent and potentially improve erectile function in patients
      suffering with ED. CONCLUSION: While intriguing, most of the literature and
      evidence is not completely scientifically compelling as to how modifying
      lifestyle risk factors can improve erectile function. Weight loss may reverse ED
      through other mechanisms, namely, decreased inflammation, increased serum
      testosterone levels, and improved mood and self-esteem. Currently, the evidence
      at hand recommends that patient education should be aimed at increasing exercise,
      reducing weight to achieve a body mass index less than 30 kg/m(2), and stopping
      smoking to improve or restore erectile function, mainly in men without
      established comorbidities. When comorbidities are present, lifestyle
      modifications may be important in preventing or reducing sexual dysfunction.
      These modifications may include precise glycemic control in diabetic men and the
      use of pharmacologic therapies for hypertension and depression, which are less
      likely to cause sexual side effects.

PMID- 22971248
TI  - Reduction in the drusenoid retinal pigment epithelium detachment area in the dry
      form of age-related macular degeneration 2.5 years after rheohemapheresis.

PMID- 22971249
TI  - Serum cardiac troponin I concentrations in dogs with leishmaniasis: correlation
      with age and clinicopathologic abnormalities.
AB  - BACKGROUND: There is anecdotal evidence of myocardial injury in dogs with
      leishmaniasis due to generalized vasculitis and myocarditis. OBJECTIVE: The aims
      of this study were to evaluate serum concentration of cardiac troponin I (cTnI)
      as an indicator of myocardial injury in dogs with leishmaniasis and to assess the
      relationship between cTnI concentration and age, serum antibody titer, and a
      variety of blood analytes. METHODS: In this retrospective study, serum cTnI
      concentration was measured in dogs with leishmaniasis and in age-matched healthy
      dogs. Diagnosis was based on clinical signs and moderate-to-high seropositivity
      for Leishmania as measured by ELISA. Correlations between cTnI concentration and
      ELISA seropositivity, PCV, concentrations of serum creatinine, total protein,
      albumin, and globulin, albumin:globulin ratio (A/G), and urine protein:creatinine
      ratio (UPC) were investigated. The Mann-Whitney test was used to compare analytes
      between dogs with normal and increased (> 0.06 MUg/L) cTnI concentration and to
      compare cTnI concentrations between dogs with and without anemia, azotemia, and
      proteinuria. RESULTS: In dogs with leishmaniasis (n = 40), median cTnI
      concentration was higher than in control dogs (n = 11) (P = .011). Sixteen dogs
      (40%) with leishmaniasis had increased cTnI concentration; cTnI was moderately to
      weakly correlated with decreased albumin concentration, decreased A/G, increased
      UPC, decreased PCV, positive Leishmania titer, and increased age. Dogs with
      leishmaniasis had significantly higher total protein and globulin concentrations
      and lower PCV, albumin concentration, and A/G than control dogs. Hematologic and
      biochemical analytes did not differ significantly between dogs with cTnI
      concentration within the reference interval and those with increased
      concentrations. Concentration of cTnI was higher in proteinuric dogs compared
      with nonproteinuric dogs (P = .017). CONCLUSION: A proportion of dogs with
      leishmaniasis have increased serum cTnI concentration, indicative of some degree
      of cardiac injury. Additional studies are needed to investigate the relationship
      between leishmaniasis and possible myocardial injury.

PMID- 22971250
TI  - Polyphenol composition of plum selections in relation to total antioxidant
      capacity.
AB  - Dietary polyphenols are associated with protection against chronic diseases such
      as cardiovascular disease. Pharmacological studies show a range of bioactivities
      and efficacy attributable to specific polyphenols. While many fruits are rich in
      polyphenols, wide cultivar variation of polyphenol composition is common. Our
      objective was to determine the composition of major bioactive polyphenols in 29
      prevarietal selections of Western Australian plums, and Black Amber as an
      evaluation in developing breeding tools to develop fruit that may have enhanced
      health-promoting capacities. Total phenolics were quantified colorimetrically;
      selected polyphenols were quantified by HPLC; and the total antioxidant capacity
      (TAC) was measured by the antioxidant inhibition of oxygen radicals (AIOR) assay.
      Total phenolic concentration was significantly correlated with TAC (R = 0.95, P <
      0.01). Neo-chlorogenic acid and quercetin glycosides were found to be the
      predominant polyphenols (mean 29.9 mg.kg(-1) and 50.7 mg.kg(-1), respectively).
      No significant correlations were found between the composition of predominant
      polyphenols in plums and the TAC. We argue that the value of in vitro TAC assays
      to breeding programs may be limited, and future research should focus on the
      heritability of known bioactive polyphenols.

PMID- 22971251
TI  - Neutrophilic cholangitis in psoriasis vulgaris and psoriatic arthritis.

PMID- 22971252
TI  - Spontaneous correction of anterior crossbite by RPE anchored on deciduous teeth
      in the early mixed dentition.
AB  - AIM: The purpose of this study was to evaluate the effectiveness of Haas RPE
      anchored on deciduous teeth in the early mixed dentition, for inducing the
      spontaneous correction of permanent incisor's crossbite, without compliance,
      without post bite-plane and no involvement of the permanent teeth. MATERIALS AND
      METHODS: The sample group comprised 50 consecutive patients (mean age 8y 5m, SD
      2y 1m), 31 males, 19 females. They showed a cross-bite affecting one or more
      permanent incisors, for a total of 70 teeth. The patients were treated with Haas
      RPE appliance anchored on second deciduous molars and bonded on deciduous
      canines. No direct forces were applied on the permanent teeth. RESULTS: Anterior
      crossbite self-corrected 'spontaneously' in 84% of the cases. Lateral incisors
      had a higher rate of self-correction than central incisors. All hyper-divergent
      subjects showed a spontaneous crossbite self-correction. CONCLUSION: The early
      maxillary expansion by Haas RPE anchored on deciduous teeth is an efficient and
      effective procedure to induce the anterior crossbite self-correction in the early
      mixed dentition without the need of a bite-plane, no involvement of the permanent
      teeth and without compliance.

PMID- 22971253
TI  - Does oral health counseling effectively improve oral hygiene of orthodontic
      patients?
AB  - AIM: The aim of this study was to compare the effectiveness of oral health
      counseling sessions with traditional oral hygiene education in orthodontic
      patients with fixed appliances. MATERIALS AND METHODS:  STUDY DESIGN: randomised
      control trial with experimental and control group. A  group of 99 adolescents
      with fixed orthodontic appliances were randomly assigned to oral health
      counseling (experimental) or traditional health education (control) group.
      Subjects in the control group received verbal instructions and a demonstration of
      the modified Bass brushing technique on a model. The experimental group also
      received the verbal information with demonstration on the model and in addition a
      personalised 40-minutes counseling session on oral hygiene. Plaque Index (PI) and
      gingivitis (G) were recorded before, 1 and 6 months after the counseling
      session/traditional education. RESULTS: Oral health counseling and traditional
      education improved the oral hygiene of orthodontic patients. PI values were
      significantly lower after 6 months compared to the baseline in both groups, but
      the prevalence of gingival inflammation remained significantly lower only in the
      experimental group. CONCLUSION: Oral health counseling increased plaque removal
      efficacy and control of gingival inflammation. The efficiency of counseling and
      traditional education was similar. Counseling is a promising approach that
      warrants further attention in a variety of dental contexts.

PMID- 22971254
TI  - Awareness of orthodontists regarding oral hygiene performance during active
      orthodontic treatment.
AB  - AIM: The aim of the present study was orthodontist's awareness for maintenance of
      several home and professional prevention measures during active orthodontic
      treatment according to patients' report. MATERIALS AND METHODS: A structured
      questionnaire was distributed to 122 patients undergoing active orthodontic
      treatment with fixed appliances. Patients were treated by 38 different
      orthodontists. The questionnaire accessed information regarding instructions
      patients received from their orthodontist concerning maintenance of their oral
      hygiene during orthodontic treatment. RESULTS: Most of the patients (94%)
      reported that their orthodontists informed them at least once about the
      importance of tooth-brushing, and 74.5% received instructions for correct
      performance of tooth brushing or alternatively were referred to dental hygienist.
      However, only 24.5% of the patients reported that their orthodontist instructed
      them to use the correct fluoride concentration in their toothpaste, to use daily
      fluoride mouthwash (31.5%) and to brush their teeth once a week with high
      concentration of fluoride gel (Elmex gel; 10.2%). Only 13.8% received application
      of high concentration of fluoride gel or varnish at the dental office, and 52% of
      the patients reported that their orthodontist verified that they attend regular
      check-ups by their dentist. A significant positive correlation was found between
      explaining the patients the importance of tooth brushing and the following
      variables:  instructing them on how to brush their teeth correctly (p<0.0001),
      explaining them which type of toothbrush is recommended for orthodontic patients
      (p=0.002), recommending to perform daily fluoride oral rinse (p=0.036) and
      referring them to periodic check-ups (p=0.024). CONCLUSION: Orthodontists should
      increase their awareness and commitment for instructing their patient on how to
      maintain good oral hygiene in order to prevent caries and periodontal disease
      during orthodontic treatment.

PMID- 22971255
TI  - Class II malocclusion division 1: a new classification method by cephalometric
      analysis.
AB  - AIM: The purpose of this study was to analyse the craniofacial and dentofacial
      skeletal characteristics in untreated subjects with Class II, division 1
      malocclusion by mandibular retrusion and to identify different types and their
      prevalence. MATERIALS AND METHODS: In 152 subjects with Class II, division 1
      malocclusion by mandibular retrusion, the differences were determined by lateral
      cephalograms analysis of variance and chi-square test, respectively. P<0.05 was
      considered significant. Seven types of mandibular retrusion were identified:
      three pure, dimensional, rotational and positional, and four mixed. RESULTS: All
      patients showed significant inter-group differences with P between 0.005 and
      0.001. The dimensional type was the most common (28.9%) and the rotational
      positional type was the rarest (5.9%). The pure dimensional type had the shortest
      mandibular body; the pure rotational type had larger SN/GoMe and the lowest AOBO;
      the pure positional type presented the flattest cranial base, high AOBO. In the
      mixed types, dento-skeletal features changed depending on how the main types
      assorted. CONCLUSIONS: Identifying the type of mandibular retrusion is important
      for differential diagnosis in clinical practice and research.

PMID- 22971256
TI  - In vitro effects  of several surface preparation methods on shear bond strength
      of orthodontic brackets to caries-like lesions of enamel.
AB  - AIM: The aim of this study was to evaluate the efficiency of several surface
      preparation methods for improving shear bond strength of brackets to
      demineralised enamel. MATERIALS AND METHODS:  STUDY DESIGN: in vitro study.
      Eighty premolars were selected and divided into 5 groups. Group 1 served as the
      control, while the remaining 4 groups were immersed in a demineralising solution
      (pH 4.8) for 12 weeks. In groups 1 (control) and 2 (demineralised/control)
      conventional acid etching was used. In group 3, a solution of 5% sodium
      hypochlorite (NaOCl) was applied on enamel surface for one minute after acid
      etching. The brackets in group 4 were bonded with Transbond Plus self-etching
      primer, and group 5 underwent treatment with a 2% sodium fluoride (NaF) gel,
      which was applied on the enamel surface for 4 minutes before etching. Shear bond
      strength (SBS) and adhesive remnant index (ARI) were determined in all groups,
      and surface morphology was examined under scanning electron microscope (SEM).
      RESULTS: The mean SBS of acid-etched demineralised enamel was significantly lower
      than that of acid-etched sound enamel (p<0.05). Treatment of caries-like lesions
      with 5% NaOCl or self-etching primer failed to improve the bond strength. After
      NaF treatment and acid etching of demineralised enamel, both type 1 and type 2
      etching patterns were observed and the resulting SBS was comparable to that of
      sound enamel (p>0.05). CONCLUSION: The application of 2% NaF on enamel caries
      before bracket bonding is an effective way for enhancing the bond strength.

PMID- 22971257
TI  - Shear bond strength of orthodontic brackets bonded to deciduous teeth with
      different etching times.
AB  - AIM: This was to compare shear bond strength (SBS) of brackets bonded to
      deciduous teeth with that of permanent teeth, to evaluate  the effect of
      increasing etching time on the SBS of brackets bonded to deciduous teeth and to
      evaluate the modes of bond failure after de-bonding. STUDY DESIGN: ex vivo 
      study. MATERIALS AND METHODS: A total of 120 freshly extracted human maxillary
      teeth were divided into six groups of 20 teeth each as follows: Group 1,
      permanent canines with 15-second etching time; Group 2, first premolars with 15
      second etching time; Group 3, deciduous canines with 15-second etching time;
      Group 4, deciduous first molars with 15-second etching time; Group 5, deciduous
      canines with 30-second etching time; Group 6, deciduous first molars with 30
      second etching time. After bonding, all specimens were thermocycled from 5 
      degrees C to 55  degrees C and back to 5  degrees C 500 times. The modified ARI
      was used to determine the mode of bond failure. STATISTICS: Comparison between
      groups was performed using Univariate General Linear Model (UGLM) and chi-squared
      tests. RESULTS: SBS for permanent and deciduous teeth etched for 15 seconds
      averaged 106.60 +/- 34.69 N and 96.90 +/- 28.51 N, respectively. SBS for
      deciduous teeth etched for 15 seconds (91.90 +/- 32.90 N and 101.80 +/- 23.12 N
      for canines and molars respectively) and 30 seconds (110.40 +/- 30.11 N and 94.20
      +/- 25.74 N for canines and molars, respectively). No significant differences
      were recorded between the different groups. Bond failure at the enamel-adhesive
      interface occurred more frequently in the deciduous teeth groups, while failure
      at bracket-adhesive interface occurred more frequently in the permanent teeth
      group. CONCLUSION: SBS of brackets bonded to deciduous teeth was comparable to
      that of permanent teeth.

PMID- 22971258
TI  - Atypical deglutition: diagnosis and interceptive treatment. A clinical study.
AB  - AIM: The aim of this study was to evaluate the early treatment of atypical
      deglutition, by analysing the efficacy of the eruptive guide appliance Habit
      CorrectorTM. MATERIALS AND METHODS: The pre- and post-treatment (T1 and T2)
      cephalometric data of 2 groups of patients (G1 and G2), both consisting of 25
      patients each and treated with Habit CorrectorTM, were compared. The first group
      included 10 males and 15 females, aged between 4 and 7 years old, with average
      age 6.17 years, and therefore undergoing the last phase of primary dentition and
      the first phase of mixed dentition. The second group included 12 males and 13
      females, aged between 8 and 12 years old, with average age 9.19 years old,
      undergoing the second phase of mixed dentition. The overall duration of the
      treatment was 12 months. RESULTS: The results showed significant differences
      between the two groups, with respect to overbite, overjet, molar relation,
      inclination of the upper and lower incisors, position of the jaw. A significant
      variation between the two groups at T2 was registered for the maxillomandibular
      relationships: the increase in the growth and degree of mandibular protrusion was
      of 4.66 degrees  in G1 and 2.44 degrees  in G2. Significant changes were
      registered for the position or growth of the upper jaw; the upper facial height
      almost remained unaltered, with 53.34 degrees  for G1 and with 53.96 degrees  for
      G2. A significant variation occurred with the increase in the sagittal
      relationship between the molars, improved in G1 by 3.14 mm and in G2 by 2.61 mm.
      A significant decrease of overjet was registered in G1 by 1.94 mm and in G2 by
      0.76 m and an increase of overbite in G1 by 3.14 mm and in G2 by 0.88 mm. The
      inclination of the maxillary and mandibular incisors improved, with an inter
      incisive angle of 123 degrees  in G1 and 124.2 degrees  in G2. CONCLUSION: The
      clinical results obtained suggest that early intervention in atypical deglutition
      with Habit CorrectorTM is able to produce significant results in primary
      dentition and in the first phase of mixed dentition, rather than in the late
      phase of mixed dentition.

PMID- 22971259
TI  - Rapid maxillary expansion: effects on palatal area investigated by computed
      tomography in growing subjects.
AB  - AIM: The aim of this prospective study was to evaluate the effects of rapid
      maxillary expansion (RME) on the palatal area as assessed by low-dose CT before
      treatment (T0), at the end of active expansion (T1) and after a retention period
      of 6 months (T2). MATERIALS AND METHODS: The study sample comprised 17
      prepubertal subjects (mean age 11.2 years) with constricted maxillary arches.
      Total amount of expansion was 7 mm in all subjects. Multi-slice low-dose CT scans
      were taken at T0, T1, and T2. On axial CT scanned images a circle line
      corresponding to the palatal area was drawn and the area inside the circle
      registered at all three observation times. The area was measured in mm2.
      Statistical comparisons were carried out with Friedman test with post-hoc tests
      (P<0.05). RESULTS: The palatal area showed a significant increase from T0 to T1
      and from T0 to T2 as a consequence of the opening of the midpalatal suture after
      RME. CONCLUSION: Opening the midpalatal suture by using orthopedic forces allowed
      to extend the area of the maxilla. After a 6-months retention period the palatal
      area demonstrated a stable increase due to a bone deposition along the midpalatal
      suture in both the anterior and posterior parts of the maxilla.

PMID- 22971260
TI  - Acceptance and discomfort in growing patients during treatment with two
      functional appliances: a randomised controlled trial.
AB  - AIM: To evaluate the levels of acceptance and discomfort between two types of
      functional appliances. STUDY DESIGN: Randomised controlled trial. MATERIALS AND
      METHODS: A sample of patients who met the inclusion criteria were distributed
      randomly and equally into two groups: the Trainer for KidsTM made up of 26
      patients with an average age of 10.3 years  (Group A), and the modified Activator
      with 28 patients, with an average age of 10.6 years (Group B), as control. A
      special questionnaire including eight questions about tension, pressure,
      sensitive teeth, pain, impaired speech, impaired swallowing, oral constraint and
      lack of confidence in public caused by the appliance was administered at T1 (7
      days), T2 (14 days), T3 (3 months), and T4 (6 months). RESULTS: The sensation of
      pressure, teeth sensitivity, pain and impaired speech declined significantly in
      Group A. All complaints decreased significantly in Group B, but the changes in
      'lack of confidence in public' were not significant. Moreover the sensation of
      pressure, teeth sensitivity, oral constraint and impaired speech were
      significantly higher in Group A than in Group B. CONCLUSION: The modified
      Activator caused less discomfort than the Trainer for KidsTM and was more
      acceptable.

PMID- 22971261
TI  - Orthopaedic treatment efficiency in skeletal Class III malocclusions in young
      patients: RME-face mask versus TSME.
AB  - AIM: To cephalometrically compare the skeletal vertical and sagittal effects of
      TSME with those of RME protraction facemask therapy in Class III patients.
      MATERIALS AND METHODS: The sample of this retrospective study included 104
      patients (53 females, 51 males) with age ranging from 5 to 9 years, presenting a
      skeletal Class III relationship: 52 were treated with transverse sagittal
      maxillary expander (TSME) appliance (Group 1) and 52 with Hyrax rapid maxillary
      expander/facemask (RME/FM, Group 2). For each patient a lateral cephalogram was
      obtained before treatment (T0) and at the end of the retention period (T1).
      Changes in the two groups during the observation period were calculated, compared
      and statistically analysed with t-test. RESULTS: TSME can produce skeletal
      changes and dento-alveolar modifications. RME in association with protraction
      facemask showed that after treatment the maxilla was moved significantly forward.
      The correction of the ANB angle was due to a change in mandibular position during
      treatment which showed a backward and downward rotation. CONCLUSION: Both devices
      were effective in the treatment of subjects with skeletal Class III due to
      maxillary retrusion.

PMID- 22971262
TI  - Primary enamel permeability: a SEM evaluation in vivo.
AB  - AIM: The aim of this study was to evaluate in vivo the occurrence of outward
      fluid flow on primary tooth sound enamel surface. MATERIALS AND METHODS: Sixty
      primary upper canines from preadolescent patients (mean age 8.0+/-1.9)  and 24
      retained primary upper canines from adult subjects (mean age 35.0+/-1.8) were
      analysed. The enamel surface was gently polished and air dried for 10 s. An
      impression was immediately obtained by vinyl polyxiloxane. Replicas were then
      obtained by polyether impression material, gold coated and inspected under SEM.
      The hydrophobic vinyl polyxiloxane material enabled to obtain in situ a
      morphological image of the presence of droplets, most likely resulting from
      outward fluids flow through outer enamel. For each sample three different 
      representative areas of 5MU2 in the cervical, medium and incisal third  were
      examined and droplets presence values was recorded. All data were analysed by by
      Fisher's exact test. RESULTS: Primary enamel showed a substantial permeability
      expressed as droplets discharge on its surface. Droplets distribution covered,
      without any specific localisation, the entire enamel surface in all the samples.
      No signs of post-eruptive maturation with changes in droplets distribution were
      observed in samples from adult subjects. No statistically significant differences
      (P = 0.955)  were noted in the  percentage distribution of enamel area covered
      with droplets among the two group studied. CONCLUSION: SEM evaluation of droplets
      distribution on enamel surface indicated a substantial enamel permeability in
      primary teeth, accordingly with histological features, without changes during
      aging. A relationship between enamel permeability, caries susceptibility and
      bonding procedures effectiveness could be hypothesised.

PMID- 22971263
TI  - A rare case of unerupted second deciduous molar located inferior to the second
      premolar: case report.
AB  - AIM: Tooth eruption is defined as the movement of a tooth from its site of
      development within the alveolar process to its functional position in the oral
      cavity [Massler et al., 1941]. The process of tooth eruption can be divided into
      different phases: pre-eruptive bone stage, alveolar bone stage, mucosal stage,
      preocclusal stage, occlusal stage and maturation stage [Andreasen et al., 1997].
      Any disturbance in these phases can lead to eruptive anomalies. The incidence of
      unerupted teeth is usually higher among permanent teeth than among deciduous ones
      [Walker et al., 2004; Otsuka et al., 2001; Amir et al., 1982; Broadway, 1976;
      Pinborg et al., 1970]. Of the primary teeth reported as unerupted, second primary
      molars are the teeth most frequently involved [Walker et al., 2004; Otsuka et
      al., 2001; Bianchi et al., 1991; Ranta et al., 1988; Tsukamoto et al., 1986; Amir
      et al., 1982], followed by primary central incisors [Otsuka et al., 2001]. CASE
      REPORT: This paper presents a case of inversion of the intraosseous position of a
      second unerupted deciduous molar and the succedaneous second premolar.

PMID- 22971264
TI  - Aesthetic restoration of upper lip after removal of post-trauma foreign body
      (orthodontic bracket).
AB  - AIM: Approach to dental trauma should always be based on a careful examination of
      the traumatised area, including both hard and soft tissues, to ascertain the
      presence of a foreign body and to assess the best treatment and follow-up. In
      this work a case of an orthodontic bracket migrated to the upper lip and retained
      there for 10 years, following a trauma is discussed. CASE REPORT: The patient
      complained symptomatic swelling of the upper lip; palpation and x-rays showed the
      presence of a foreign body, identified as an orthodontic bracket. Medical history
      revealed that patient had a dental trauma 10 years prior. The foreign body was
      localised and removed. At the two week follow-up visit after surgical incision of
      the lip, signs and symptoms (i.e. the swollen lip) were resolved. This case
      emphasises the importance of accurate  management of the traumatic event, through
      proper diagnosis and therapy of both hard and soft tissues, even if the
      examination if the patient is performed years after the dental trauma.

PMID- 22971265
TI  - Patients treated with orthodontic-myofunctional therapeutic protocol.
AB  - AIM: The aim of this study is to report  three  cases that needed myofunctional
      and orthodontic treatment and the good results achieved after the therapy.
      Orthodontic treatment alone, in presence of bad habits, is not enough to solve
      the orthodontic issues, so it needs to be combined with myofunctional treatment.

PMID- 22971266
TI  - Non-compliant maxillary protraction by  orthodontic micro-implants.
AB  - AIM: Delaire-type facemask is still the appliance of choice for non surgical
      paediatric Class III treatment. However, it entails great aesthetical problems
      and is totally dependent on patient compliance. A new modified maxillary
      protractor was then designed: it is monomaxillary, fixed, implant-supported,
      aesthetically pleasing and it does not require patient compliance. The aims of
      this study were to evaluate the clinical use and analyse the effects of a new
      appliance called Fixed Maxillary Protractor. The device aims at obtaining a
      forward movement of the maxillary dento-alveolar component in non-compliant
      paediatric patients, when mandible retrusion cannot be pursued. CASE REPORT: A
      non-compliant patient aged 4 years 11 months with mild skeletal and predominant
      dento-alveolar Class III malocclusion with maxillary deficiency, anterior
      crossbite and complete deciduous dentition was treated for 10 months. The
      appliance, anchored by 2 micro-implants in the posterior palatal region,
      consisted of an acrylic plate, a lingual splint, 2 TMA springs that delivered a
      posterior-anterior force, 2 anterior security devices and 2 occlusal bite raising
      splints on the deciduous molars. The treatment yielded a slightly overcorrected
      Class I incisal relationship. Increase in SNA angle (2 degrees ) and a decrease
      in SNB angle (1 degrees ) resulted in an increase in ANB angle (3 degrees ).
      Increases in Wits appraisal of 4 mm and in overjet of 7 mm were obtained. A
      correction of the anterior crossbite the a posterior sliding of the mandible due
      to the crossbite correction were observed. An anticlockwise rotation of the
      maxilla and a mild increase in the anterior facial height were achieved: the
      treatment effects are similar to those obtained with the Delaire-type facemask,
      but the amount of postero-anterior correction is lower. DISCUSSION AND
      CONCLUSION: The Fixed Maxillary Protractor is effective for the treatment of mild
      moderate Class III malocclusion with maxillary deficiency in non-compliant
      paediatric patients.

PMID- 22971267
TI  - Slugging their way to immortality: driving mammary epithelial cells into a stem
      cell-like state.
AB  - Delineating the molecular factors that define and maintain the mammary stem cell
      state is vital for understanding normal development and tumourigenesis. A recent
      study by Guo and colleagues identifies two master transcriptional regulators of
      mammary stem cells, Slug and Sox9, ectopic expression of which confers stem cell
      attributes on differentiated mammary epithelial cells. Slug and Sox9 expression
      was also shown to determine in vivo metastatic potential of human breast cancer
      cell lines. Understanding these factors in the context of normal lineage
      differentiation is an important step toward elucidating the mammary epithelial
      cell hierarchy and the origins of cancer stem cells. 

PMID- 22971269
TI  - Post-discharge mortality in patients hospitalized with MRSA infection and/or
      colonization.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection is known to increase
      in-hospital mortality, but little is known about its association with long-term
      health. Two hundred and thirty-seven deaths occurred among 707 patients with MRSA
      infection at the time of hospitalization and/or nasal colonization followed for
      almost 4 years after discharge from the Atlanta Veterans Affairs Medical Center,
      USA. The crude mortality rate in patients with an infection and colonization
      (23.57/100 person-years) was significantly higher than the rate in patients with
      only colonization (15.67/100 person-years, P = 0.037). MRSA infection,
      hospitalization within past 6 months, and histories of cancer or haemodialysis
      were independent risk factors. Adjusted mortality rates in patients with
      infection were almost twice as high compared to patients who were only colonized:
      patients infected and colonized [hazard ratio (HR) 1.93, 95% confidence interval
      (CI) 1.31-2.84]; patients infected but not colonized (HR 1.96, 95% CI 1.22-3.17).
      Surviving MRSA infection adversely affects long-term mortality, underscoring the
      importance of infection control in healthcare settings.

PMID- 22971268
TI  - RNA-Seq reveals complex genetic response to Deepwater Horizon oil release in
      Fundulus grandis.
AB  - BACKGROUND: The release of oil resulting from the blowout of the Deepwater
      Horizon (DH) drilling platform was one of the largest in history discharging more
      than 189 million gallons of oil and subject to widespread application of oil
      dispersants. This event impacted a wide range of ecological habitats with a
      complex mix of pollutants whose biological impact is still not yet fully
      understood. To better understand the effects on a vertebrate genome, we studied
      gene expression in the salt marsh minnow Fundulus grandis, which is local to the
      northern coast of the Gulf of Mexico and is a sister species of the
      ecotoxicological model Fundulus heteroclitus. To assess genomic changes, we
      quantified mRNA expression using high throughput sequencing technologies (RNA
      Seq) in F. grandis populations in the marshes and estuaries impacted by DH oil
      release. This application of RNA-Seq to a non-model, wild, and ecologically
      significant organism is an important evaluation of the technology to quickly
      assess similar events in the future. RESULTS: Our de novo assembly of RNA-Seq
      data produced a large set of sequences which included many duplicates and
      fragments. In many cases several of these could be associated with a common
      reference sequence using blast to query a reference database. This reduced the
      set of significant genes to 1,070 down-regulated and 1,251 up-regulated genes.
      These genes indicate a broad and complex genomic response to DH oil exposure
      including the expected AHR-mediated response and CYP genes. In addition a
      response to hypoxic conditions and an immune response are also indicated. Several
      genes in the choriogenin family were down-regulated in the exposed group; a
      response that is consistent with AH exposure. These analyses are in agreement
      with oligonucleotide-based microarray analyses, and describe only a subset of
      significant genes with aberrant regulation in the exposed set. CONCLUSION: RNA
      Seq may be successfully applied to feral and extremely polymorphic organisms that
      do not have an underlying genome sequence assembly to address timely
      environmental problems. Additionally, the observed changes in a large set of
      transcript expression levels are indicative of a complex response to the varied
      petroleum components to which the fish were exposed.

PMID- 22971270
TI  - Small cell osteosarcoma with Ewing sarcoma breakpoint region 1 gene rearrangement
      detected by interphase fluorescence in situ hybridization.
AB  - Because of its characteristic morphologic appearance, small cell osteosarcoma
      (SCO) can be confused with other small round cell malignancies of the bone, most
      importantly with Ewing sarcoma, making this distinction difficult. A specific
      tool used in separating SCO from Ewing sarcoma has been the detection of Ewing
      sarcoma breakpoint region 1 (EWSR1) gene rearrangements in Ewing sarcoma and
      their absence in SCO. However, there are rare case reports that have documented
      the existence of EWSR1 gene rearrangement in SCO. In this report, we describe
      another case of SCO with an EWSR1 gene rearrangement detected by interphase
      fluorescence in situ hybridization. Our finding adds support to the existing
      evidence that SCO is a tumor that can be characterized by EWSR1 gene
      arrangements. Therefore, we caution the pathology community not to rely solely on
      molecular studies in distinguishing SCO from Ewing sarcoma. 

PMID- 22971271
TI  - Alternative approaches to expanding pediatric urology services and productivity.
AB  - PURPOSE: We critically assessed the outcomes of a new model of pediatric urology
      delivery using alternative approaches to expand care without increasing the
      number of pediatric urologists. The approaches included the use of advanced
      practice nurse practitioners, pediatric physician specialists, part-time contract
      pediatric urologists from neighboring institutions and part-time contract adult
      urologists from our university. MATERIALS AND METHODS: Data were collected from
      the Division of Pediatric Urology at Arkansas Children's Hospital during 2009 and
      2010. The only pediatric urologist at our institution retired in December 2009
      with an immediate transition to a new pediatric urologist in January 2010.
      Comparisons were made in the numbers of clinic visits, inpatient
      admissions/consultations, surgical volume and patient satisfaction scores.
      RESULTS: Average clinic monthly visits in 2009 and 2010 were 153 and 271,
      respectively (p <0.0001). Inpatient admissions increased from 43 in 2009 to 162
      in 2010. Inpatient initial consultations and followup consultations increased by
      115 and 112, respectively, from 2009 to 2010. Surgical volume increased 26.7% in
      2010 (p = 0.0832) and Press Ganey(r) scores were comparable or improved from 2009
      to 2010. CONCLUSIONS: The use of advance practice nurse practitioners, part-time
      contract adult and pediatric urologists, and pediatric physician specialists can
      effectively increase the number of patients treated without adding full-time
      pediatric urology staff. The assignment of patient and disease populations to
      each team member has been an ongoing process of critically defining and updating
      responsibilities in an attempt to expand care, increase productivity and maximize
      the quality of delivery of these services.

PMID- 22971272
TI  - A micelle-shedding thermosensitive hydrogel as sustained release formulation.
AB  - In this paper it is shown that when a thermosensitive hydrogel based on poly(N
      isopropylacrylamide)-poly(ethylene glycol)-poly(N-isopropylacrylamide) (pNIPAm
      PEG-pNIPAm) was transferred into water, flower-like micelles were continuously
      released as long as the medium was regularly refreshed. On the other hand, if the
      medium was not refreshed the concentration of micelles reached an equilibrium.
      When this gel was loaded with the cytostatic agent paclitaxel (PTX), the released
      micelles solubilized PTX, as evidenced by a PTX concentration in the release
      medium above its aqueous solubility. To test the applicability of these micelle
      releasing gels for sustained and systemic delivery of PTX an in vivo experiment
      was performed in tumor-bearing mice. pNIPAm-PEG-pNIPAm gels (without and with
      1.2% and 6.0% PTX loading) were administered i.p. in nude mice bearing 14C human
      squamous cell carcinoma tumor xenografts to obtain doses corresponding to one and
      five times the maximum tolerated dose of PTX (when given i.v. as the standard
      formulation in Cremophor EL/ethanol). All gel formulations were well tolerated
      and no signs of acute systemic toxicity were observed. After injection of the
      highest dose, PTX levels in serum could be determined for 48 h with a
      comparatively long elimination half-life of 7.4 h pointing to a sustained release
      of PTX. A bioavailability of 100% was calculated from the area under the curve of
      plasma concentration vs time. Furthermore, at the highest dose, PTX was shown to
      completely inhibit tumor growth for at least 3 weeks with a single hydrogel
      injection. This promising concept may find application as a depot formulation for
      sustained, metronomic dosing of chemotherapeutics.

PMID- 22971273
TI  - Chronic noise exposure causes persistence of tau hyperphosphorylation and
      formation of NFT tau in the rat hippocampus and prefrontal cortex.
AB  - The non-auditory effects of noise exposure on the central nervous system have
      been established both epidemiologically and experimentally. Chronic noise
      exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's
      disease (AD)-like pathological changes. However, experimental evidence for these
      associations remains limited. The aim of the current study was to explore the
      effects of CNE [100 dB sound pressure level (SPL) white noise, 4 h/d*14 d] on tau
      phosphorylation in the rat hippocampus and the prefrontal cortex. Forty-eight
      male Wistar rats were randomly assigned to two groups: a noise-exposed group and
      a control group. The levels of radioimmunoprecipitation assay (RIPA)-soluble and
      RIPA-insoluble phosphorylated tau at Ser202, Ser396, Ser404, and Ser422 in the
      hippocampus and the prefrontal cortex were measured at different time points
      (days 0, 3, 7, and 14) after the end of the last noise exposure. Exposure to
      white noise for 14 consecutive days significantly increased the levels of tau
      phosphorylation at Ser202, Ser396, Ser404, and Ser422, the sites typically
      phosphorylated in AD brains, in the hippocampus and the prefrontal cortex. Tau
      hyperphosphorylation persisted for 7 to 14 d after the cessation of noise
      exposure. These alterations were also concomitant with the generation of
      pathological neurofibrillary tangle (NFT) tau 3, 7 and 14 d after the end of the
      stimulus. Furthermore, lasting increases in proteins involved in
      hyperphosphorylation, namely glycogen synthase kinase 3beta (GSK3beta) and
      protein phosphatase 2A (PP2A), were found to occur in close correspondence with
      increase in tau hyperphosphorylation. The results of this study show that CNE
      leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed
      formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our
      results also provide evidence for the involvement of GSK3beta and PP2A in these
      processes.

PMID- 22971274
TI  - Quantitative assessment of invasive mena isoforms (Menacalc) as an independent
      prognostic marker in breast cancer.
AB  - INTRODUCTION: Mena, an Ena/VASP protein family member, is a key actin regulatory
      protein. Mena is up-regulated in breast cancers and promotes invasion and
      motility of tumor cells. Mena has multiple splice variants, including Mena
      invasive (MenaINV) and Mena11a, which are expressed in invasive or non-invasive
      tumor cells, respectively. We developed a multiplex quantitative
      immunofluorescence (MQIF) approach to assess the fraction of Mena lacking 11a
      sequence as a method to infer the presence of invasive tumor cells represented as
      total Mena minus Mena11a (called Menacalc) and determined its association with
      metastasis in breast cancer. METHODS: The MQIF method was applied to two
      independent primary breast cancer cohorts (Cohort 1 with 501 and Cohort 2 with
      296 patients) using antibodies against Mena and its isoform, Mena11a. Menacalc
      was determined for each patient and assessed for association with risk of disease
      specific death. RESULTS: Total Mena or Mena11a isoform expression failed to show
      any statistically significant association with outcome in either cohort. However,
      assessment of Menacalc showed that relatively high levels of this biomarker is
      associated with poor outcome in two independent breast cancer cohorts (log rank P
      = 0.0004 for Cohort 1 and 0.0321 for Cohort 2). Multivariate analysis on combined
      cohorts revealed that high Menacalc is associated with poor outcome, independent
      of age, node status, receptor status and tumor size. CONCLUSIONS: High Menacalc
      levels identify a subgroup of breast cancer patients with poor disease-specific
      survival, suggesting that Menacalc may serve as a biomarker for metastasis.

PMID- 22971276
TI  - [Correlation study of estrogen receptor with peripheral blood cytokines and serum
      markers in primary biliary cirrhosis patients].
AB  - OBJECTIVE: To investigate the correlation between ER-a in the liver and cytokines
      of T lymphocytes subsets and serum signatures in PBC patients. METHODS: The
      research is performed with cross-sectional study. 80 PBC women patients without
      treatment were enrolled in PBC group, 10 healthy women as baseline-matched in
      healthy-control group, and 20 patients with non-autoimmune liver disease in non
      PBC control group. The expression of IL-6, IL-8, IL-22, TNFa, IFNgamma, AMA-M2,
      Sp100 and gp210 were analyzed in Peripheral Blood using ELISA in all groups, and
      ER-a of patients were performed on tissues from liver biopsies in PBC group and
      non-PBC control group with immunohistochemistry. Spearman correlation test were
      performed on the indices to identified the association of all Parameters.
      numerical data were compared with Wilcoxon rank-sum test. RESULTS: Compared with
      healthy-control group, expression of serum cytokines are significantly higher in
      PBC and non-PBC groups (P less than 0.01), while no significant difference were
      observed between PBC and non-PBC groups. The positive rate of ER-a in PBC
      patients liver tissues in PBC group is higher than that in non-PBC group (Z=4.82,
      P less than 0.01). Expression of ER-a is positively correlated with positive
      rates of AMA-M2 antibody, Sp100 and gP210 of tissues of PBC patients ( r=0.898,
      0.819, 0.814, P less than 0.01). ER-a is positive correlated with the expression
      of cytokines, among which the coefficient of correlation of IL-22, TNFa, IFNgamma
      is more than 0.7 (r=0.71, 0.89, 0.82, P less than 0.01), AMA-M2, Sp100, gp210 is
      negative in serum of non-PBC control group. No obviously correlations were
      indicated between the expression of ER-a and cytokines. CONCLUSION: A high level
      of expression of cytokines in the serum might be one of the factors of
      etiopathogenesis of PBC.

PMID- 22971277
TI  - [Clinical and pathological features of autoimmune hepatitis: no significant
      differences between genders].
AB  - To explore the clinical and pathological features of male and female autoimmune
      hepatitis (AIH) patients. METHODS: One hundred and sixty-nine AIH patients were
      enrolled. The clinical and histological data of the male cases were compared with
      the female ones. RESULTS: There were 23 (13.6%) male patients in our study. The
      general status, biochemical and immunological test, and histological findings
      between two groups had no significant difference (P more than 0.05). The IAIHG's
      revised original scoring system pretreatment scores of male patients (14.4+/-2.3)
      were lower than that of female ones (16.6+/-2.6, Z= -3.728, P=0.000), whereas the
      simplified scoring system scores of male patients (7.2+/-0.8) were higher than
      that of female ones (6.5+/-1.2, Z=-2.372, P=0.018). There were 15 male AIH
      patients treated with immunosuppressive therapy, then 12 of them reached complete
      biochemical remission, the other three cases were incomplete response. The
      complete biochemical remission rate in our male cases was 80%. Median duration of
      remission was 3 months (95% CI 2.070-3.930 months). CONCLUSION: There are no
      significant differences in clinical and pathological features of AIH between
      genders. The diagnosis of AIH should be suspected in male patients with any
      abnormality in serum aminotransferases levels. Liver biopsy examination is
      recommended to establish the diagnosis of AIH. The simplified criteria have good
      diagnostic value for male AIH patients.

PMID- 22971278
TI  - [The therapeutic effect of Anluohuaxian capsule combined with adefovir dipivoxil
      on patients with chronic hepatitis B and influence on hepatic histology].
AB  - To observe the efficacy of adefovir dipivoxil(ADV) in combination with
      Anluohuaxian capsule in the treatment of chronic hepatitis B (CHB) patients.
      METHODS: 72 cases with CHB were randomly divided into two groups. 36 cases of
      treatment group were given ADV combined with Anluohuaxian capsule for 48 weeks.
      36 cases of control group were given ADV. The levels of serum ALT, AST, Alb,
      TBil, HA, LN, CIV, HBV DNA and hepatic tissue were compared before and after
      being treated. RESULTS: After 48 weeks treatment,the liver function, serum
      fibrosis index and histology of treatment group and control group all have
      improved. After treatment, the two groups in the levels of ALT(t=0.746, P=0.342),
      AST (t=0.369, P=0.713), TBil (t=0.146, P=0.684), Alb(t=0.148, P=0.883), liver
      tissue inflammation mobility scoring (t=1.666, P=0.100) and HBV DNA negative rate
      (x2=0.141, P=0.708) were no evident difference.The level of HA, LN, CIV were
      significantly lower in treatment group(101.58+/-30.11, 147.89+/-41.72, 38.75+/
      9.50) compared with control group(182.25+/-117.59, 181.50+/-56.96, 74.92+/-31.14)
      (P less than 0.05). After the treatment, the liver tissue fibrosis scoring was
      significantly lower in treatment group (10.61+/-2.37) compared with before the
      treatment (12.28+/-3.16) (P less than 0.05).There was no difference found between
      after the treatment (11.36+/-2.93) and before the treatment (12.17+/-3.01) in
      control group (P more than 0.05). CONCLUSIONS: The results show that the
      treatment with ADV in combination with Anluohuaxian capsule can play promoting
      antifibrotic effect and significant improved liver histology of chronic hepatitis
      B patients.

PMID- 22971279
TI  - [Characteristic of liver pathology in HBeAg-positive and HBeAg-negative chronic
      hepatitis B patients with mildly elevated ALT].
AB  - To analyse the live pathology characteristics in mild ALT-elevated (1 x ULN less
      than ALT less than 2 x ULN ) HBeAg-positive and HBeAg-negative chronic hepatitis
      B (CHB) patients, and to explore the influence of the age and HBV DNA level to
      liver pathology in different HBeAg status patients. METHODS: All the patients who
      met the inclusion criteria form "eleventh five-year plan" National Science and
      Technology Major Project, the treatment program of integrative traditional and
      western medicine for CHB were enrolled in this study between October 2009 and
      March 2011 .B type ultrasound-guided liver biopsy was carried out in all patients
      and hepatitis B surface antigen (HBsAg) , HBeAg titer as well as HBV DNA level
      were detected at the same time. Hepatic tissue inflammation and fibrosis degree
      of patients according to HBeAg-positive and negative, age ( more than or equal to
      40 years and less than 40 years), HBV DNA level (more than or equal to
      10^5copy/ml and less than l0^5 copy/ml) were compared respectively. Chi-square
      test was used to compare the constitute percentage between the two samples.
      Multivariate logistic regression analysis was also performed to evaluate the
      correlation between different factors. RESULTS: There were no significant
      difference in the grade of liver inflammation and the stage of liver fibrosis
      between 389 HBeAg positive and 126 HBeAg-negative patients (X2=4.326 and
      X2=3.464, respectively, P values were all more than 0.05). In the group of
      patients with age less than 40 years, the distribution of different liver
      inflammation and fibrosis had no significant difference between HBeAg-positive
      and negative patients (X2=2.543 and X2=5.024, respectively, P values were all
      more than 0.05). In the group of patient with age more than or equal to 40 years,
      the percentage of moderate and severe inflammation (G3, G4) HBeAg-positive
      patients(32.9%) owned is much higher than that of HBeAg-negative patients(16.4%),
      X2=8.777, P less than 0.05.But the stage of liver fibrosis in HBeAg-positive
      patients was not significantly different than that of HBeAg-negative ones
      (X2=0.977, P more than 0.5). In the group of patients with HBV DNA more than or
      equal to 10^5copy/ml, the percentage of mild inflammation in HBeAg-positive
      patients (17.5%) was much high than that of HBeAg-negative patients(7.3%),
      X2=8.851, P less than 0.05. The stage of liver fibrosis between HBeAg-positive
      and negative patients was no significant difference (X2=8.227, P more than
      0.05).In the patients with HBV DNA less than 10^5 copy/ml, The percentage of
      HBeAg-negative patients(29.6%) with mild inflammation(G1) was much higher than
      HBeAg-positive patients (6.9%), X2=6.357, P less than 0.05. There was no
      significant difference in the stage of liver fibrosis between HBeAg-positive and
      negative patients (X2=4.061, P more than 0.05). The results of multivariate
      logistic regression analysis showed that age was the independent risk factor for
      different degree of liver inflammation and fibrosis seriousness. CONCLUSION: The
      status of HBeAg has no association with the grade of liver inflammation and the
      stage of liver fibrosis in CHB patients with mildly elevated ALT. The percentage
      of moderate and severe inflammation in the HBeAg-positive patients with age more
      than or equal to 40 years was significantly elevated. The grade of liver
      inflammation has significant difference between HBeAg-positive and negative
      patients with different HBV DNA levels as well.

PMID- 22971280
TI  - [Long-term assessment of relapse and associated risk factors in chronic hepatitis
      C patients treated with interferon and ribavirin].
AB  - OBJECTIVE: To investigate viral relapse and the associated risk factors during a
      long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end
      of-treatment response (ETR) after interferon and ribavirin therapy. METHODS: This
      retrospective study was conducted on 146 CHC patients treated with a combination
      of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional
      IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype
      1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors
      analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type.
      RESULTS: The mean follow-up time for all patients was 33.45+/-16.41 months
      (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%.
      The relapse rate within six months (8.90%) was significantly higher than other
      periods during two years of follow-up, and no relapse occurred after 30 months.
      Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7
      24 months after antiviral therapy. The relapse rates in patients with HCV
      genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2
      =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the
      relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were
      similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs.
      13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers
      was significantly higher than that of non-relapsers (P less than 0.005).
      CONCLUSION: The maximum probability of relapse for CHC patients exists within six
      months from when ETR is achieved by interferon and ribavirin therapy. A lower
      risk for relapse persists past this period. Thus, ETR CHC patients, especially
      older patients, should be carefully monitored during the two years after
      cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype
      eliminates the influence of viral factors on treatment-response.

PMID- 22971281
TI  - [Efficacy and safety of a protease inhibitor with pegylated interferon and
      ribavirin in patients with untreated chronic hepatitis C: a meta analysis].
AB  - OBJECTIVE: To compare the efficacy and safety of a double therapy containing
      pegylated interferon and ribavirin to a triple therapy (with addition of a
      protease inhibitor) for untreated chronic hepatitis C with genotype 1 infection.
      METHODS: We searched Pub med, EMBASE, OVID, the Cochrane Library Clinical Trials
      Registry and included relevant randomized controlled trials for comparing the
      efficacy and safety of the triple therapy to the double therapy in HCV genotype 1
      untreated patient, using terms: protease inhibitor, hepatitis C, genotype 1. The
      primary endpoints were composed of the rates of SVR, the rates of relapse, the
      rates of anemia, and the rates of discontinuation due to severe adverse events,
      respectively. RESULTS: Five trials (involving a total of 3200 patients) were
      included. Data showed the triple therapy with either telaprevir or boceprevir
      significantly increased the SVR rate and decreased the relapse rate compared with
      the double therapy [for SVR rate, 65.4% vs. 40.9%, OR=2.92, 95% CI 2.5 to 3.42, P
      less than 0.01, and for relapse rate, 11.3% vs. 24.8%, OR=0.42, 95% CI 0.26 to
      0.68, P less than 0.01], but the triple therapy associated with higher side
      effects and intolerability [ higher anemia rate, 44.1 % vs. 26.2%, OR=2.25, 95%
      CI 1.9 to 2.65, P less than 0.01 and higher discontinuation rate owing to severe
      adverse events, 12.4% vs. 7.7%, OR=1.66, 95% CI 1.19 to 2.32, P less than 0.01].
      Subgroup analysis found that the rates of SVR were still higher and the relapse
      rates were lower in all triple treatment groups [composed by 24 (or 28) -week
      groups, 48-week groups, and response-guided therapy groups] than that of the
      double therapy. CONCLUSION: A triple therapy with peginterferon-ribavirin plus
      either boceprevir or telaprevir significantly increased the rate of sustained
      virologic response among untreated patients infected with hepatitis C genotype 1.
      Both the incidence of adverse events and the frequency of discontinuation owing
      to severe adverse events were higher in patients receiving the triple therapy
      than those receiving the standard double therapy.

PMID- 22971282
TI  - [A systematic review and meta-analysis of randomized controlled trails : adjuvant
      interferon therapy for hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the efficacy and safety of adjuvant interferon (IFN)
      therapy for viral hepatitis related hepatocellular carcinoma(HCC) after the
      treatment of resection, ablation or TACE. METHODS: PUBMED, EMBASE, Cochrane
      Library, CNKI, CBM, Wan fang Data were searched, plus some manual search and
      searching on the internet for grey literature. The studies that according to the
      standards were included, then Meta-analysis were done. RESULTS: Eight studies
      (n=857, 442 treated with IFN) were eligible for this study, pooled data showed
      benefit of IFN for the prevention of HCC recurrence, 1-year [RR=0.71, 95% CI
      (0.51, 0.99)], 3-year [RR=0.86, 95% CI (0.76-0.98)], 4-year [RR=0.79, 95% CI
      (0.68-0.91)]. IFN showed benefit for improving 1-year and 2-year survival, 1-year
      [RR=1.09, 95% CI (1.01-1.18)], 2-year [RR=1.25, 95% CI (1.04-1.50)]. The
      difference on 2-year, 5-year recurrence rate are without statistical
      significance, the same to 3-year, 4-year, 5-year survival rate. CONCLUSION: IFN
      therapy after the treatment of resection, ablation or TACE can probably reduce
      HCC recurrence rate and improve survival with acceptable toxicities.

PMID- 22971283
TI  - [Hepatitis C virus F protein-mediated inhibition of hepatoma cell proliferation].
AB  - OBJECTIVE: To investigate the biological function of the hepatitis C virus (HCV)
      encoded F protein in hepatocytes. METHODS: The full-length F gene was amplified
      by PCR from HCV genotype 1a and cloned into plasmid pSEB-3Flag by restriction
      enzyme digestion and ligation. Hepatoma cell lines, Huh7 and SMMC7721, were
      transfected with the resultant recombinant pSEB-3Flag-F or the original pSEB
      3Flag (negative control) and screened with the selective antibiotic, blasticidin.
      Stable F gene and protein expression was verified by RT-PCR analysis. Analysis of
      cell growth and cell cycle was carried out by MTS assay, crystal violet staining
      and flow cytometry. RESULTS: Huh7 and SMMC7721 cells transfected with pSEB-3Flag
      F plasmid (Huh7-F and SMMC7721-F, respectively) uniquely expressed the F gene and
      protein. The Huh7-F and SMMC7721-F cells showed significantly decreased
      proliferation rates, compared to the respective control groups. A similar HCV F
      mediated growth-inhibiting activity was observed by the cell viability assay.
      Furthermore, cell cycle analysis revealed that the S-phase distribution was much
      lower in Huh7-F (47.12%) and SMMC7721-F (30.75%) cells than in the respective
      controls (55.35% and 33.23%, respectively) (P less than 0.05). CONCLUSION: Stable
      expression of the HCV F gene reduced the in vitro proliferation rate of hepatoma
      cell lines, indicating that the F protein may function as a growth inhibitor of
      infected cells.

PMID- 22971284
TI  - [Biological function explore of protein CCL15 in HCC cell lines].
AB  - To explain biological function of protein CCL15 in HCC cell lines. The different
      expression level of CCL15 among HCC cell lines was validated by RT-PCR and
      Western blot. The expression recombinant plasmid of siRNA-CCL15 was constructed
      successfully and transfected into high metastasis cell lines HCCML3 to observe
      the alteration of biological function of HCCML3. The overexpression of CCL15 in
      high metastasis HCC cell lines was confirmed by validation tests. After
      transfected with siRNA-CCL15, the average amounts of invaded cells in cell
      invasion assay were 657.9 (HCCML3) and 148.4(HCCML3-siCCL15) (t=19.34, P less
      than 0.05). And in the scratch assay, the migrating distance were (0.35+/-0.02)
      mm (HCCML3) and (0.82+/-0.03)mm (HCCML3-siCCL15) (t=15.67, P less than 0.05). The
      expression of MMP-9 in HCCML3 was higher than HCCML3-siCCL15 through Western
      blot. Some biological properties (migration, invasion, MMP-9) of HCCML3
      transfected with siRNA-CCL15 were decreased. The results suggest CCL15 might play
      an important role in HCC cell invasion and metastasis through two paths of MMPs
      regulation and invasion potential strengthening.

PMID- 22971285
TI  - [Acetoacetate extract from Celastrus orbiculatus Thunb inhibits growth of RFP
      xenografted human liver carcinoma].
AB  - To investigate the inhibitory effect of acetoacetate extract from Celastrus
      orbiculatus Thumb (COT) on the growth of red fluorescent protein (RFP)
      xenografted human hepatocellular carcinoma (HCC) in a nude mouse model. Human HCC
      HepG2 cells were transduced with RFP and inoculated into the liver of BALB/c nude
      mice. The tumor-bearing mice were randomly divided into five groups: control
      group (G1), oxaliplatin positive control group (G2; 25 mg/kg), COT low-dose group
      (G3; 20 mg/kg), COT high-dose group (G4; 40 mg/kg), and COT early treatment group
      (G5; 20 mg/kg). The early treatment group received oral COT from day 2 post-tumor
      implantation. All other mice were treated from day 20 post-tumor implantation.
      Growth of xenografted tumors was monitored weekly by in vivo real-time
      fluorescence imaging technology. At the end of the four-week treatment period,
      all mice were sacrificed and tumor tissues were collected and weighed. The two
      sided t-test was used to evaluate intergroup differences in tumor volumes, final
      tumor weights, and final body weights. Mice treated with COT had significantly
      smaller xenografted tumors. On day 45 post-implantation, the mean tumor volumes
      (mm3) in the different groups were: G1, 803.1+/-512.3 ; G2, 83.8+/-23.5; G3,
      852.7+/-502.6; G4, 410.0+/-231.6; and G5, 120.5+/-60.1. The mean tumor weights
      (g) were: G1, 0.95+/-0.49; G2, 0.36+/-0.09; G3, 0.67+/-0.29; G4, 0.48+/-0.15; and
      G5, 0.38+/-0.11. The differences in tumor weights from G2, G4 and G5 were
      significantly less than the weight in G1 (P less than 0.05); however, there was
      no significant differences between the tumor weights in G2, G4 and G5 (P more
      than 0.05). The tumor weight from the G2 group was significantly less than that
      of the G3 group (P less than 0.05). COT significantly inhibited the proliferation
      of human HCC in a nude mouse model. Early treatment with COT produced a more
      robust inhibitory effect, which was very similar to that achieved with
      oxaliplatin treatment.

PMID- 22971286
TI  - [Prospective study of the association between fasting glucose concentrations and
      liver cirrhosis risk].
AB  - OBJECTIVE: To investigate the association between concentration levels of fasting
      serum glucose and liver cirrhosis. METHODS: A nested case-control study was
      carried out based on the sample cohort from the Nutrition Intervention Trials
      previously conducted in one country in Henan province. Using an automatic
      biochemical analysis system and enzyme-linked immunoassay, baseline serum samples
      from 310 liver cirrhosis patients and 620 healthy controls were tested for
      fasting glucose concentration, hepatitis B surface antigen (HBsAg), hepatitis B
      core antibody (anti-HBc), and hepatitis C virus antibody (anti-HCV). Baseline
      demographic information was collected by questionnaire. The serum glucose values
      were divided into quintiles and applied to a logistic regression model to
      estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The
      mean fasting blood glucose level was significantly higher in cases (4.5+/-1.8
      mmol/L) than in controls (4.2+/-2.1 mmol/L) (t=-2.414, P=0.016). The individuals
      in the highest quintile had a significantly higher risk of disease than those in
      the lowest quintile [OR=1.672 (1.080, 2.588)]. Moreover, increase in glucose
      level was accompanied by increased risk, and the relation showed statistically
      significant linearity (P=0.002). The statistical significance of risk remained
      after adjustment for potential confounders, including sex, age, HBsAg, anti-HBc,
      and residence running water status [OR=1.96 (1.216, 3.157), P=0.001]. CONCLUSION:
      Elevated serum fasting glucose concentration was an independent risk factor of
      cirrhosis.

PMID- 22971287
TI  - [Real-time elastography for quantitative assessment of liver fibrosis in a rat
      model].
AB  - OBJECTIVE: To investigate the feasibility of real-time elastography for
      quantitative evaluation of liver fibrosis in a rat model. METHODS: A total of 70
      male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced
      liver injury, and 10 saline-injected rats were used as normal control. Hepatic
      injury was induced by a single intraperitoneal injection of DMN at a dose of 50
      mg/kg of body weight. Nine or ten rats in the group with DNM injected and one or
      two rats in the normal control group were randomly selected and sacrificed at
      each of the following post-injection time: day 5, 7, 10, 14, 21, 24, and 28. And
      their livers were taken for pathology analysis. All the rats underwent real-time
      elastography before sacrificed in order to acquire area ratio of low-strain
      region (% AREA) and liver fibrosis index (LF index) which were compared with the
      stage of liver fibrosis and grade of necroinflammatory pathologically. By the
      different data, Spearman correlation analysis, rank-sum test or receiver
      operating characteristic curve was used. RESULTS: Among 58 successfully modeled
      rats, there were nine, 13, 14 and 12 rats of S1, S2, S3 and S4 liver fibrosis on
      pathology, respectively, which were with or without mild necroinflammatory. The
      other 10 rats were found to be S0 with severe necroinflammatory. Values of LF
      index and % AREA both increased with liver fibrosis stage (P less than 0.05).
      There was certain correlation between LF index and liver fibrosis stage (r=0.643,
      P=0.000), so was % AREA and liver fibrosis stage (r=0.662, P=0.000). As for LF
      index, Areas under the receiver operating characteristic curve (Az) was 0.943,
      0.890, 0.743 and 0.821 for the diagnosis of hepatic fibrosis S1 or higher, S2 or
      higher, S3 or higher and S4, respectively; as for % AREA, they were 0.948, 0.883,
      0.772 and 0.842, respectively. However, we found a significant difference for LF
      index or % AREA between S0 with and without severe inflammatory activity rats
      (P=0.005 and P=0.017). CONCLUSION: Real-time elastography is available for
      quantitative assessment of liver fibrosis in rats induced by DMN, but severe
      inflammatory activity can affect its accuracy.

PMID- 22971288
TI  - The Hospital Anxiety and Depression Scale: low sensitivity for depression
      screening in demented and non-demented hospitalized elderly.
AB  - BACKGROUND: We currently use the depression subscale (HADD) of the Hospital
      Anxiety and Depression Scale (HADS) for depression screening in elderly
      inpatients. Given recent concerns about the performance of the HADD in this age
      group, we performed a quality-control study retrospectively comparing HADD with
      the diagnosis of depression by a psychiatrist. We also studied the effect of
      dementia on the scale's performance. METHODS: HADS produces two 7-item subscales
      assessing depression or anxiety. The HADD was administered by a
      neuropsychologist. As "gold standard" we considered the psychiatrist's diagnosis
      based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, criteria. Patients older than 65 years, assessed by both the HADD and
      the psychiatrist, with a clinical dementia rating (CDR) score lower than 3, were
      included. The effect of dementia was assessed by forming three groups according
      to the CDR score (CDR0-0.5, CDR1, and CDR2). Simple and multiple logistic
      regression models were applied to predict the psychiatrist's depression diagnosis
      from HADD scores. Areas under the receiver operating characteristics curve (AUC)
      were plotted and compared by chi(2) tests. RESULTS: On both univariate and
      multiple analyses, HADD predicted depression diagnosis but performed poorly
      (univariate: p = 0.009, AUC = 0.60 (95% confidence interval (CI) = 0.53-0.66);
      multiple: p = 0.007, AUC = 0.65 (95% CI = 0.58-0.71)), regardless of cognitive
      status. Because mood could have changed between the two assessments (they
      occurred at different points of the hospital stay), the multiple analyses were
      repeated after limiting time interval at 28, 21, and 14 days. No major
      improvements were noted. CONCLUSION: The HADD performed poorly in elderly
      inpatients regardless of cognitive status. It cannot be recommended in this
      population for depression screening without further study.

PMID- 22971290
TI  - [Type 2-diabetes--a coherent health care system needed].

PMID- 22971291
TI  - [Type 2 diabetes in Denmark].
AB  - Our vision is that the opportunistic screening system will be improved in order
      to find patients with occult type 2 diabetes (T2D), since an early treatment
      based on a correct phenotyping is the goal. Individual goals for HbA1c, blood
      pressure and lipids must be set up, and the number of drugs used must fit with
      the patient's phenotype to avoid polypharmacy. A new flow chart for the
      organisation of T2D has been formulated giving the general practitioners the role
      as co-ordinators.

PMID- 22971289
TI  - Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in
      estrogen receptor-negative breast cancer.
AB  - INTRODUCTION: The Ets-1 transcription factor is a candidate breast cancer
      oncogene that regulates the expression of genes involved in tumor progression and
      metastasis. Ets-1 signaling has also been linked to the development of a basal
      like breast cancer phenotype. We recently described a nitric oxide (NO)-induced
      gene signature that is associated with poor disease outcome in estrogen receptor
      negative (ER-) breast cancer and contains both stem cell-like and basal-like
      components. Thus, we examined the role of Ets-1 in NO signaling and NO-induced
      phenotypes in ER- human breast cancer cells. METHODS: Promoter region analyses
      were performed on genes upregulated in inducible nitric oxide synthase (NOS2)
      high expressing tumors for Ets-binding sites. In vitro mechanisms were examined
      in human basal-like breast cancer cells lines. NO signaling effects were studied
      using either forced NOS2 expression or the use of a chemical NO-donor,
      diethlylenetriamine NONOate (DETANO). RESULTS: Promoter region analysis of genes
      that are up-regulated in human ER-negative breast tumors with high NOS2
      expression revealed that the Ets-binding sequence is the only common promoter
      element present in all of these genes, indicating that Ets-1 is the key
      transcriptional factor down-stream of oncogenic NOS2-signaling. Accordingly, both
      forced NOS2 over-expression and exposure to NO-donors resulted in significant Ets
      1 transcriptional activation in ER- breast cancer cells. Functional studies
      showed that NO activated Ets-1 transcriptional activity via a Ras/MEK/ERK
      signaling pathway by a mechanism that involved Ras S-nitrosylation. RNA knock
      down of Ets-1 suppressed NO-induced expression of selected basal-like breast
      cancer markers such as P-cadherin, S100A8, IL-8 and alphabeta-crystallin.
      Additionally, Ets-1 knock-down reduced NO-mediated cellular proliferation, matrix
      metalloproteinase and cathepsin B activities, as well as matrigel invasion.
      CONCLUSIONS: These data show that Ets-1 is a key transcriptional mediator of
      oncogenic NO signaling that promotes the development of an aggressive disease
      phenotype in ER- breast cancer in an Ets-1 and Ras-dependent manner, providing
      novel clues of how NOS2 expression in human breast tumors is functionally linked
      to poor patient survival.

PMID- 22971292
TI  - [Type 2 diabetes--a heterogeneous disease with a foetal predisposition].
AB  - Type 2 diabetes (T2D) is a heterogeneous disease with a multifactorial aetiology
      involving defects in the pancreatic beta cells, liver, muscles, adipose tissue,
      guts, brain, kidneys and heart. While genetics may only explain a minor
      proportion of T2D, the contribution of an adverse intrauterine environment may
      take centre stage in the global propagation of T2D. Impaired expandability of
      subcutaneous adipose tissue in persons with low birthweight may cause T2D due to
      lipotoxicity in non-adipose organs. Future implications include a stronger focus
      on individualized treatments in T2D patients and prevention of T2D in the next
      generations.

PMID- 22971293
TI  - [New pharmacological treatment methods of type 2 diabetes].
AB  - The variable pathogenesis and progressive nature of type 2 diabetes emphasise the
      need for new antidiabetic treatments. The long acting glucagon-like peptide-1
      receptor agonists and dipeptidyl peptidase-4 inhibitors have improved the
      treatment. Novel approaches include inhibitors of sodium glucose co-transporter
      2, which increase renal glucose elimination, G-protein-coupled receptor agonists,
      which potentiate insulin and incretin hormone secretion. Proof of principle has
      been shown for glucagon receptor agonists, glucokinase activators and treatment
      with dual intestinal peptides, which all induce weight loss and improve glucose
      tolerance.

PMID- 22971294
TI  - [Eye complications in type 2 diabetes mellitus].
AB  - Diabetic retinopathy frequently causes blindness, especially in patients with
      type 2 diabetes mellitus (T2D). The implementation of systematic screening can
      improve the visual prognosis significantly, and recently decision models that
      allow individualised determination of control intervals on the basis of known
      risk factors have been introduced. Current treatment of diabetic retinopathy with
      retinal photocoagulation has adverse effects with severe consequences for
      patients with T2D. However, recently intravitreal angiostatic therapy has been
      introduced as an effective new modality for the treatment of diabetic
      retinopathy.

PMID- 22971295
TI  - [Renal disease by type 2 diabetes].
AB  - Diabetic nephropathy is the leading cause of end stage renal disease in the
      Western world. 30-35% of the patients with type 2 diabetes will have micro- or
      macroalbuminuria, warranting yearly screening. Treatment to prevent diabetic
      nephropathy is multifactorial, adressing known progression promoters such as
      blood pressure, glycaemia, dyslipidaemia and smoking and includes antithrombotic
      prophylaxis. Although progress has been made over the last few decades, there is
      still an unmet need for improved screening, prevention and treatment since both
      cardiac and renal morbidity and mortality remains severe in this group of
      patients.

PMID- 22971296
TI  - [The prevalence of type 2-diabetes in ethnic minorities].
AB  - In general, type 2 diabetes is more common among immigrants than among the
      inhabitants with a Western background. The higher prevalence among ethnic
      minorities is probably due to a complex correlation between genetic factors,
      diet, exercise, linguistic and cultural obstacles, low birthweight and high catch
      up weight as well as socio-economic factors. Ethnic minorities are heterogeneous,
      and individual initiatives within the different groups are needed. The evidence
      regarding the effect of initiatives targeted at ethnic minorities in Denmark is
      sparse. In future, clinically controlled studies in this field should be carried
      out.

PMID- 22971297
TI  - [Organization of treatment and control of type 2 diabetic patients].
AB  - The organization of treatment and control of type 2 diabetic patients in Denmark
      has undergone a major development within the last decade. From being based on
      local hospital guidelines, treatment and control have moved towards a more
      organized collaboration between primary and secondary care based on common
      national guidelines. Quality indicators from primary and secondary care are
      collected routinely, and gradually an increasingly precise depiction is
      documented in the National Indicator Project.

PMID- 22971298
TI  - Cross-cultural ageism: ageism and attitudes toward aging among Jews and Arabs in
      Israel.
AB  - BACKGROUND: While it is generally agreed that traditional societies are more
      favorable toward their elders, research findings have been inconsistent.
      Accordingly, this study presents a cultural comparison between Jews and Arabs in
      Israel in attitudes toward older adults and personal views regarding one's own
      aging. It was assumed that Arabs would rate their culture as more tolerant toward
      older adults, would report spending more time with them, and express lower ageism
      and aging anxieties. METHOD: We examined 154 native Israeli citizens, 86 Jewish
      and 68 Muslim Arabs, who completed measures of ageism, aging anxieties, and
      cultural views of older adults. RESULTS: Arabs rated their culture as more
      tolerant toward their elders, perceived older adults as significantly more
      contributing to society, and reported engaging in less avoiding behaviors toward
      them. Arabs also exhibited less general fears of growing old and concerns over
      one's physical appearance in old age. But it was interesting to note that Arab
      women reported higher scores of aging anxieties and ageist attitudes in
      comparison to Arab men, whereas no such differences were found among Jews.
      CONCLUSIONS: Our findings point that the cultural importance of elders for the
      Arab cohort transcends beyond Westernization processes which affect the Arab
      society in Israel, and reflect the demanding role of Arab women as primary
      caregivers for the elders in the family. Limitations and implications of the
      study are discussed.

PMID- 22971299
TI  - Increasing awareness of sepsis: World Sepsis Day.

PMID- 22971300
TI  - The role of predisposition to hallucinations on non-clinical paranoid vs.
      socially anxious individuals after hearing negative affective-laden sounds: an
      experimental investigation.
AB  - BACKGROUND: Research suggested that negative affective-laden sounds act as
      environmental stressors that elicit negative affect (Bradley and Lang, 2000a).
      AIMS: We tried to test for the role of an interaction between predisposition to
      hallucinatory experiences and exposure to negative affective laden sounds for the
      presence of paranoid ideation. METHOD: We used an experimental design that
      followed the vulnerability * stress model. We defined three groups from a sample
      of students: paranoia group vs. social anxiety group vs. control group. Their
      psychological characteristics were measured through self-reports of paranoia,
      anxiety, predisposition to hallucinations and depressive symptoms at Time 1
      (before the experiment). Participants had to listen to either negative affective
      laden sounds (e.g. screaming) or positive affective laden sounds (e.g. sound of
      ocean waves). Their paranoid ideation and positive vs. negative emotional
      reactions to sounds were measured through self-reports at Time 2 (after the
      experiment). RESULTS: Data showed that the paranoia group presented more serious
      psychological vulnerabilities than the social anxiety group. A MANCOVA also
      showed that the independent variables ("group" and "experimental sound
      conditions") had statistically significant main effects on general paranoia
      ideation at Time 2. Furthermore, there was a significant three-way interaction
      between group x predisposition to hallucinatory experiences * experimental
      condition of sounds for the presence of general paranoid ideation at Time 2.
      Limitations included the small sample size and the effects of parasite variables,
      e.g. noise. CONCLUSIONS: Individuals' predisposition for hallucinatory
      experiences increases the probability of possessing paranoid ideation. This
      tendency is a characteristic of paranoid non-clinical individuals.

PMID- 22971301
TI  - Successful treatment of localized pyoderma gangrenosum with topical 
      pimecrolimus.

PMID- 22971302
TI  - Capecitabine-induced inflammation of actinic keratosis: case report and
      literature review.

PMID- 22971303
TI  - The coexistence of psoriasis and vitiligo: a review.
AB  - BACKGROUND: Psoriasis and vitiligo are both autoimmune diseases with an increased
      incidence noted in genetic relatives. They share similar trigger factors and have
      been observed to coexist in individuals. OBJECTIVE: The purpose was to review the
      literature on the coexistence of psoriasis and vitiligo and to determine if there
      is a higher than expected prevalence of psoriasis in patients with vitiligo and
      vice versa. METHODS: A literature review was conducted using Medline, EMBASE, and
      the Cochrane Library from 1968 to 2010. All articles that included reports of
      individuals with both psoriasis and vitiligo in the English language were
      documented. RESULTS: We identified 338 articles, among which 35 case reports and
      7 case series were mentioned. For each case series, the prevalence of psoriasis
      in patients with vitiligo, or vice versa, falls within the prevalence range of
      the background population on which the study was based. CONCLUSION: An increase
      in the expected prevalence of psoriasis in individuals with vitiligo, or vice
      versa, was not found in our study, suggesting that the coexistence of the two
      diseases appears to be due to chance alone. Large epidemiologic studies are
      required to address with certainty whether psoriasis is more common in
      individuals with vitiligo and vice versa.

PMID- 22971304
TI  - Agreement between dermatologists and primary care practitioners in the diagnosis
      of malignant melanoma: review of the literature.
AB  - BACKGROUND: The incidence of melanoma continues to rise in the developed world.
      It is therefore essential for primary care practitioners (PCPs) to be able to
      discriminate between malignant and benign cutaneous findings, as most patients
      present to PCPs first for examination of suspicious lesions. OBJECTIVE: To
      compare dermatologists and PCPs in the diagnosis of malignant melanoma. METHODS:
      Prospective studies published from January 1950 to August 2010 in MEDLINE,
      EMBASE, CINAHL, and CancerLit databases were examined. Relevant medical search
      terms, discussed amongst the authors, were entered into the databases. Only
      articles comparing dermatologists and PCPs in the diagnosis of malignant melanoma
      were selected. RESULTS: Dermatologists were reported as having sensitivities,
      specificities, and diagnostic accuracies ranging from 0.74 to 1.00, 0.56 to 0.95,
      and 0.85 to 0.89, respectively. PCPs had sensitivities, specificities, and
      diagnostic accuracies ranging from 0.25 to 0.88, 0.26 to 0.71, and 0.49 to 0.80,
      respectively. CONCLUSIONS: PCPs should receive more training to improve their
      ability in the diagnosis of malignant melanoma.

PMID- 22971305
TI  - Erythropoietic protoporphyria: spectrum of three cases.
AB  - BACKGROUND: Erythropoietic protoporphyria is a rare photodermatosis of childhood,
      and the diagnosis can be delayed. A deficient ferrochelatase enzyme leads to
      accumulation of protoporphyrins in the dermis, causing phototoxic burning.
      OBJECTIVE: To report three cases with great variability in severity of symptoms
      and age at diagnosis. We discuss clinical and biochemical findings, mutation
      analysis, and therapeutic options. METHODS: We report three cases with different
      degrees of photosensitivity, laboratory results, psychosocial impact, and
      preventive and therapeutic treatments. RESULTS: The diagnosis of erythropoietic
      protoporphyria was confirmed by both typical elevation of plasma porphyrins and
      the discovery of a mutated FECH gene. CONCLUSION: Erythropoietic protoporphyria
      should be suspected in any cases of childhood photosensitivity. Systemic
      complications are unusual. Mutation analysis confirms the diagnosis.
      Photoprotection is the cornerstone of treatment.

PMID- 22971306
TI  - Propranolol in the treatment of problematic infantile hemangioma: review of 35
      consecutive patients from a vascular anomalies clinic.
AB  - BACKGROUND: Propranolol, a nonselective beta-blocker, has been reported as
      efficient for controlling the growth of complicated infantile hemangiomas (IHs).
      No uniformly accepted protocol exists regarding the administration of oral
      propranolol for IH. OBJECTIVE: We sought to share our experience using
      propranolol for problematic IH and to evaluate the efficacy of this treatment
      modality. METHODS: A retrospective chart review analysis was performed for 35
      consecutive children treated with propranolol as an oral solution on an
      outpatient basis in our dermatology/vascular anomalies clinic. A protocol was
      established with the help of our pediatric cardiologists, including pretreatment
      electrocardiography and echocardiography. Medical photographs taken after 2
      months of treatment were rated by two independent evaluators. RESULTS: We treated
      31 girls and 4 boys with a median age of 3.5 months. Rapid improvement was
      reported in the first days of treatment in 34 patients. Mean improvement after 2
      months was 61.5%. No serious adverse effects were reported. CONCLUSION:
      Propranolol was effective in controlling the proliferative phase of problematic
      IH. It was well tolerated in our study. Outpatient treatment is possible if
      parents follow strict guidelines. Propranolol should be a first-line treatment
      for problematic IH in carefully selected patients.

PMID- 22971307
TI  - Prospective study of topical 5-aminolevulinic acid photodynamic therapy for the
      treatment of moderate to severe acne vulgaris in Chinese patients.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) mediated with 5-aminolevulinic
      acid (ALA) offers an alternative option for the treatment of acne vulgaris.
      OBJECTIVE: To study the effects of ALA dose, incubation time, and lesion type on
      protoporphyrin IX (PpIX) production and treatment outcomes. METHODS: To examine
      the time course of PpIX production, 10% ALA was applied to inflammatory papules
      for 1 to 5 hours and followed by in situ fluorescence examination. To determine
      the effects of ALA dose and lesion type, 3, 5, and 10% ALA was applied to acne
      lesions in split-face fashion for 3 hours followed by whole-face light
      irradiation at 633 nm and 30 to 70 J/cm2. Treatment was repeated twice at 2-week
      intervals. RESULTS: PpIX reached a stable level after 3 hours of incubation.
      Similar PpIX levels were seen in areas receiving 3, 5, and 10% ALA. Poisson
      regression analyses indicated that lesion counts decreased by 0.791 times for a
      one-unit increase in treatment times (95% CI 0.782-0.799 < .0001) but only by
      0.999 times for a one-unit increase in ALA dose (95% CI 0.998-1.000  =  .22).
      CONCLUSION: The combination of low-dose ALA and a red light is a safe and
      effective option for the treatment of moderate to severe acne.

PMID- 22971308
TI  - Public perceptions and attitudes toward vitiligo.
AB  - BACKGROUND: Previous studies have discussed attitudes of vitiligo patients toward
      their disease. However, no studies have addressed this issue from the public's
      point of view. OBJECTIVE: To explore the perceptions, attitudes, and
      misconceptions of the public toward vitiligo. METHODS: A self-administered
      questionnaire was distributed to attendees of primary health care centers in
      Riyadh, Saudi Arabia, between January and August 2010. RESULTS: Overall, 924 of
      the 1,000 distributed questionnaires were returned, and 429 were males (46.8%).
      Moreover, 33.1% (303 of 916) believed that vitiligo is contagious or did not know
      that it is not. The cause of vitiligo was thought to be infectious by 20.4% of
      respondents (182 of 894), inherited by 40.5% (365 of 902), autoimmune by 41.2%
      (370 of 899), and due to a lack of hygiene by 22.5% (199 of 883). Unmarried
      individuals and those with less education were more likely to state that vitiligo
      is caused by an infection (.  =  .02, .  =  .03, respectively). Younger
      individuals and those with less education were more likely to think that vitiligo
      is caused by a lack of hygiene (.  =  .01, .  =  .001, respectively). More than
      half of the participants (56.1%, 504 of 898) would be unwilling to marry a
      vitiligo patient. Younger individuals and males were less likely to marry a
      vitiligo patient (.  =  .01, .  =  .05, respectively), whereas those of lower
      income were more likely to accept it (.  =  .002). CONCLUSIONS: Various
      misconceptions and negative attitudes about vitiligo among the public are
      prevalent. Educating the public about vitiligo could ultimately lead to better
      psychosocial well-being of vitiligo patients.

PMID- 22971309
TI  - Malignant pilomatrixoma arising on the previously irradiated face: case report
      and literature review.
AB  - BACKGROUND: Malignant pilomatrixoma (also known as pilomatrix carcinoma) is a
      very rare malignant neoplasm derived from the hair matrix. These slow-growing
      malignancies of the skin are found in the lower dermis and subcutaneous fat
      layer. They can exhibit local aggressive behavior or distant metastasis. This
      malignancy can arise as a solitary lesion de novo or through transformation of a
      pilomatrixoma over a long period. There is no known distinct etiologic factor or
      predisposing condition for this kind of malignancy. OBJECTIVE AND CONCLUSION: We
      present an interesting case of a 65-year-old man with a pilomatrix carcinoma
      arising on the previously irradiated face due to the malignant neoplasm of the
      parotid gland. This is the first report of a pilomatrix carcinoma that has
      developed on a region that has undergone radiotherapy for another malignancy.

PMID- 22971310
TI  - Pemphigus vegetans associated with intranasal cocaine abuse.
AB  - BACKGROUND: Pemphigus vegetans is a rare variant of pemphigus vulgaris,
      comprising 1 to 2% of all pemphigus cases. Exposures to oral agents such as
      captopril and penicillamine and, less commonly, physical or chemical factors have
      been implicated in the development of pemphigus. METHODS: We report a 42-year-old
      white male with a 12-month history of hypertrophic, vegetative plaques affecting
      primarily his external nares and upper lips. The patient had a history of
      alcoholism and intermittent drug abuse, primarily intranasal cocaine, since his
      youth. He had been using cocaine heavily three to four times/week for 1 month
      prior to and 1 month following the onset of the eruption but has since ceased
      use. His clinical features and histopathologic findings were consistent with a
      diagnosis of pemphigus vegetans. Treatment with high-dose prednisone (80 mg/d)
      and mycophenolate mofetil (1.5 g/d) resulted in resolution of the lesions after
      18 months. RESULTS AND CONCLUSIONS: To our knowledge, this is the second report
      proposing an association between intranasal cocaine use and the pemphigus family
      of disorders. Although the relationship between illicit drug use and the
      development of pemphigus is unclear, we postulate that intranasal cocaine abuse
      is operative in our patient's disease. Herein we discuss drug and other external
      precipitants of pemphigus and review previous case reports of pemphigus
      associated with illicit drugs.

PMID- 22971311
TI  - Occurrence of squamous cell carcinoma in an area of lichen simplex chronicus:
      case report and pathogenetic hypothesis.
AB  - BACKGROUND: Lichen simplex chronicus is a common skin disorder characterized by
      circumscribed, lichenified, pruritic plaque secondary to local repetitive trauma,
      notably rubbing and scratching. OBJECTIVE: We describe a case of a squamous cell
      carcinoma arising in a patient with a long-lasting history of lichen simplex
      chronicus and discuss the potential role of the microenvironment in predisposing
      the malignant transformation. CONCLUSION: Here we propose a hypothesis in which
      rubbing and scratching contribute to an excess of inflammatory mediators, which
      in turn may lead to alterations in the processes of keratinocyte proliferation
      and differentiation.

PMID- 22971312
TI  - Allergic contact dermatitis from dimethyl fumarate after contact with a Chinese
      sofa.
AB  - BACKGROUND: Dimethyl fumarate has been successfully used in the treatment of
      psoriasis in the past. Despite its clinical use, cutaneous contact with this
      molecule may cause contact dermatitis. OBJECTIVE: We report a case in which skin
      exposure to a synthetic fabric sofa containing dimethyl fumarate made by a
      Chinese furniture manufacturer resulted in a severe, pruritic, papulovesicular,
      eczematous dermatitis to the sites of contact with the sofa. METHODS: The patient
      was patch-tested with serial dilutions of dimethyl fumarate. RESULTS: Patch
      testing results revealed strong positive reactions to dimethyl fumarate at
      different concentrations. CONCLUSION: Dimethyl fumarate is a potent contact
      sensitizer and is commonly found in sachets inside furniture and footwear boxes.

PMID- 22971313
TI  - Endogenous ochronosis with a fatal outcome.
AB  - BACKGROUND: Endogenous ochronosis (EO) is an autosomal recessive inherited
      disorder where there is incomplete oxidation of tyrosine and phenylalanine due to
      a lack of the enzyme homogentisic acid oxidase. OBJECTIVE: We report a singular
      observation of EO with a fatal outcome. CASE REPORT: We report the case of a 46
      year-old man born to consanguineous parents with a medical history of recurrent
      renal colic and chronic nonspecific arthropathy. On clinical examination, slate
      blue pigmentation was seen on the cheeks, forehead, and nose, as well as blue
      gray patches on all fingernails and bluish discoloration of the gums. Familial
      investigation revealed that his sister had similar pigmentation on the ears,
      hands, and fingernails. Histologic examination of a biopsy specimen from a
      pigmented lesion showed a dermal deposit of an acellular, eosinophilic material
      without cell reaction. Based on the clinical and histopathologic data, combined
      with the family medical history, our patient was considered to have EO with
      mucocutaneous, articular, and renal involvement. Unfortunately, the diagnosis was
      late because our patient died a few months later of terminal renal failure.
      CONCLUSION: Skin signs are the hallmarks of EO and must alert the clinician to
      look for involvement of vital organs.

PMID- 22971314
TI  - Atypical lupus erythematosus panniculitis progressing to antinuclear antibody
      negative systemic lupus erythematosus.
AB  - BACKGROUND: Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive
      subset of lupus erythematosus (LE). It may develop in patients with discoid or
      systemic LE or may occur as an isolated phenomenon. CASE REPORT: We describe a
      case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp.
      Subsequently, the patient progressed to antinuclear antibody-negative systemic
      LE.

PMID- 22971315
TI  - Conjunctival squamous cell carcinoma following psoriasis treatment.
AB  - BACKGROUND: Psoriasis is a relatively common inflammatory disease of the skin and
      joints. Moderate to severe psoriasis often necessitates lifelong alternating
      systemic therapies, many of which may increase the risk of nonmelanoma skin
      cancers and lymphoproliferative disorders. CASE DESCRIPTION: A 34-year-old male
      was diagnosed with squamous cell carcinoma (SCC) involving the right lower bulbar
      and palpebral conjunctiva with extension to the proximal lacrimal drainage
      system. The patient had suffered from severe psoriasis since childhood, for which
      he was on long-standing systemic cyclosporine, topical tacrolimus, and previous
      phototherapy. Margin-controlled excision of the lower half of the bulbar
      conjunctiva and lower eyelid with subsequent reconstruction was performed,
      followed by adjunctive topical mitomycin C 0.04% drops and local interferon
      injections. Cyclosporine was replaced with oral prednisolone. The patient was
      free of recurrence of SCC at 18 months. CONCLUSION: Although conjunctival SCC has
      been described following cyclosporine treatment for organ transplantation, this
      report describes a case of conjunctival SCC following lower-dose cyclosporine
      treatment for psoriasis in a patient who had previous psoralen plus ultraviolet A
      (PUVA) treatment. The conjunctival SCC should be considered in the differential
      diagnosis of new conjunctival lesions in such patients.

PMID- 22971316
TI  - Herpes zoster with cutaneous dissemination in a patient 21 years after
      splenectomy for idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Varicella-zoster virus is a member of the herpes virus family that
      causes varicella during a primary infection and herpes zoster (HZ) when
      reactivated. Patients who are immunocompromised often have atypical presentations
      of HZ and experience complications such as multidermal involvement and
      dissemination. OBJECTIVE: We report a case of disseminated HZ in an
      immunocompetent patient with a history of splenectomy for idiopathic
      thrombocytopenic purpura (ITP). Our 46-year-old female patient presented with a
      painful vesiculopapular dermatomal rash with approximately 80 other lesions
      diffusely spread over her body. She was in good health but had a splenectomy for
      ITP 21 years earlier and a history of recurrent herpes labialis. The latter led
      to the tentative diagnosis of a widespread herpes simplex infection. However,
      laboratory results confirmed a diagnosis of disseminated herpes zoster. A workup
      of the patient's immune status did not reveal any abnormalities other than the
      patient's previously noted splenectomy. CONCLUSIONS: This case adds to the two
      reports of patients developing cutaneous disseminated HZ several years after
      splenectomy. Our case serves as a reminder that patients with a history of
      splenectomy appear to be at increased risk for cutaneous dissemination of HZ.

PMID- 22971317
TI  - Effective treatment of nodular amyloidosis with carbon dioxide laser.
AB  - BACKGROUND: Nodular amyloidosis is a rare form of localized cutaneous amyloidosis
      that is characterized by nodules located on the extremities, trunk, genitalia, or
      face. In treatment regimens, many approaches have been described, including
      carbon dioxide (CO2) laser therapy. OBJECTIVE: We present a case of a 60-year-old
      white male with a 20-year history of disseminated waxy, purpuric, yellowish, and
      bullous skin lesions on the trunk and extremities. The skin changes were
      accompanied by pain during palpation and were temporarily pruritic. METHOD: Based
      on histologic and direct immunofluorescence test findings, the diagnosis of
      cutaneous nodular amyloidosis was established. Skin lesions were treated with a
      CO2 laser. During surgery, treated tissue was found to be slightly friable, and
      there was a little problem with hemostasis that correlated with amyloid
      infiltration of the dermis and blood vessels. However, after 8 weeks, we observed
      clinical improvement of all treated areas with the presence of atrophic scars. In
      the regions of laser therapy, no recurrence of the disease was observed during a
      12-month follow-up. CONCLUSION: Based on these results, we conclude that CO2
      laser has a beneficial effect in the treatment of nodular amyloidosis; however,
      surgery procedures may be associated sometimes with tissue friability and poor
      hemostasis.

PMID- 22971318
TI  - Basaloid squamous cell carcinoma of the nasal septum presenting as a primary
      cutaneous lesion.
AB  - BACKGROUND: Basaloid squamous cell carcinoma is a rare aggressive variant of
      squamous cell carcinoma, with a predilection for the head and neck region. There
      are only two case reports in the literature documenting a nasal cavity squamous
      cell carcinoma presenting as a primary cutaneous lesion. OBJECTIVE: We report a
      rare case of nasal cavity basaloid squamous cell carcinoma presenting initially
      as a nasal bridge mass. Two initial biopsies revealed features consistent with
      basal cell carcinoma and basosquamous cell carcinoma, respectively. RESULT: Final
      surgical pathology showed extensive invasive squamous cell carcinoma with
      basaloid differentiation arising from the nasal septal mucosa with extension to
      the overlying skin. The clinicopathologic features were interpreted as basaloid
      squamous cell carcinoma. CONCLUSION: We discuss the difficulties in pathologic
      diagnosis of this condition given its varied phenotypical expression. As well,
      this case emphasizes the necessity for diagnostic vigilance when assessing a
      primary cutaneous lesion as it may be a rare presentation of an underlying
      malignancy extending to the skin.

PMID- 22971319
TI  - Use of fridge magnets in an office surgical setting.

PMID- 22971320
TI  - Choice of hospital after out-of-hospital cardiac arrest--a decision with far
      reaching consequences: a study in a large German city.
AB  - INTRODUCTION: Between 1 and 31% of patients suffering out-of-hospital cardiac
      arrest (OHCA) survive to discharge from hospital. International studies have
      shown that the level of care provided by the admitting hospital determines
      survival for patients suffering from OHCA. These data may only be partially
      transferable to the German medical system where responders are in-field emergency
      medical physicians. The present study determines the influence of the emergency
      physician's choice of admitting hospital on patient outcome after OHCA in a large
      urban setting. METHODS: All data for patients collected in the German
      Resuscitation Registry for the city of Dortmund during 2007 and 2008 were
      analyzed. Patients under 18 years of age, with traumatic mechanism, and with
      incomplete charts were excluded. Admitting hospitals were divided into two
      groups: those without the capability for percutaneous coronary intervention
      (PCI), and those with PCI capability. Data were analyzed by multivariate
      statistics, taking into account the effects of mild therapeutic hypothermia
      treatment and PCI capability of the admitting hospital with respect to the
      neurological status upon hospital discharge. RESULTS: Between 2007 and 2008 a
      total of 1,109 cardiopulmonary resuscitation attempts were registered for the
      city of Dortmund, of which 889 could be included in our study. Return of
      spontaneous circulation was achieved in 360 of 889 patients (40.5%). In total,
      282 of 889 patients displayed return of spontaneous circulation during transport
      to the hospital (31.7%); 152 were transported with ongoing cardiopulmonary
      resuscitation (17.1%). Of the total 434 patients admitted to hospital, 264 were
      admitted to hospitals without PCI capability and 170 to hospitals with PCI
      capability. Multivariate analysis demonstrated a significant influence on patient
      discharge with good neurological status for those admitted to PCI hospitals (odds
      ratio 3.14 (95% confidence interval 1.51 to 6.56)), independent of receiving mild
      therapeutic hypothermia and/or PCI. Compared with patients admitted to hospitals
      without PCI capability, significantly more patients in PCI hospitals were
      discharged alive (41% vs. 13%, P < 0.001) and remained alive 1 year after the
      event (28% vs. 6%, P < 0.001). CONCLUSIONS: The choice of admitting hospital for
      patients suffering OHCA significantly influences treatment and outcome. This
      influence is independent of PCI performance and of mild therapeutic hypothermia.
      Further analysis is required to determine the possible parameters determining
      patient outcome.

PMID- 22971322
TI  - Interpersonal ambivalence in obsessive-compulsive disorder.
AB  - BACKGROUND: The social attitudes and interpersonal relationships of patients with
      obsessive-compulsive disorder (OCD) are subject to a longstanding controversy.
      Whereas cognitive-behavioural researchers emphasize exaggerated pro-social
      attitudes in OCD like inflated responsibility and worry for other people
      (especially significant others), dynamic theories traditionally focus on anti
      social attitudes such as latent aggression and hostility. In two recent studies,
      we gathered support not only for a co-existence of these seemingly opposing
      attitudes in OCD, but also for a functional connection: inflated responsibility
      in part appears to serve as a coping strategy (or "defense") against negative
      interpersonal feelings. AIMS: In the present study, we tested a shortened version
      of the Responsibility and Interpersonal Behaviours and Attitudes Questionnaire
      (RIBAQ-R). METHOD: The scale was administered to 34 participants with OCD and 34
      healthy controls. The questionnaire concurrently measures pro-social and anti
      social interpersonal attitudes across three subscales. RESULTS: In line with our
      prior studies, patients displayed higher scores on both exaggerated pro-social
      attitudes (e.g. "I suffer from a strict conscience concerning my relatives") as
      well as latent aggression (e.g. "Sometimes I would like to harm strangers on the
      street") and suspiciousness/distrust (e.g. "I cannot even trust my own family").
      A total of 59% of the patients but only 12% of the healthy controls showed marked
      interpersonal ambivalence (defined as scores higher than one standard deviation
      from the mean of the nonclinical controls on both the prosocial and at least one
      of the two anti-social subscales). CONCLUSIONS: The study asserts high
      interpersonal ambivalence in OCD. Further research is required to pinpoint both
      the dynamic and causal links between opposing interpersonal styles. Normalization
      and social competence training may prove beneficial to resolve the apparent
      problems of patients with OCD regarding anger expression and social conflict
      management.

PMID- 22971321
TI  - Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in
      mouse trigeminal primary afferent neurons innervating the dura.
AB  - BACKGROUND: Migraine and other headache disorders affect a large percentage of
      the population and cause debilitating pain. Activation and sensitization of the
      trigeminal primary afferent neurons innervating the dura and cerebral vessels is
      a crucial step in the "headache circuit". Many dural afferent neurons respond to
      algesic and inflammatory agents. Given the clear role of the transient receptor
      potential (TRP) family of channels in both sensing chemical stimulants and
      mediating inflammatory pain, we investigated the expression of TRP channels in
      dural afferent neurons. METHODS: We used two fluorescent tracers to retrogradely
      label dural afferent neurons in adult mice and quantified the abundance of
      peptidergic and non-peptidergic neuron populations using calcitonin gene-related
      peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers,
      respectively. Using immunohistochemistry, we compared the expression of TRPV1 and
      TRPA1 channels in dural afferent neurons with the expression in total trigeminal
      ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled
      dural afferent neurons in mice expressing farnesylated enhanced green fluorescent
      protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to
      predict the spatial association between dural afferent neurons and neurons
      expressing TRPA1 or TRPM8 channels in the TG. RESULTS AND CONCLUSIONS: We report
      that the size of dural afferent neurons is significantly larger than that of
      total TG neurons and facial skin afferents. Approximately 40% of dural afferent
      neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent
      neurons containing CGRP-ir is significantly lower than those of total TG neurons
      and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural
      afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1
      expressing neurons are clustered around a subset of dural afferent neurons.
      Interestingly, TRPM8-expressing neurons are virtually absent in the dural
      afferent population, nor do these neurons cluster around dural afferent neurons.
      Taken together, our results suggest that TRPV1 and TRPA1 but not TRPM8 channels
      likely contribute to the excitation of dural afferent neurons and the subsequent
      activation of the headache circuit. These results provide an anatomical basis for
      understanding further the functional significance of TRP channels in headache
      pathophysiology.

PMID- 22971324
TI  - Can deworming delay immunosuppression in HIV?

PMID- 22971323
TI  - Empiric deworming to delay HIV disease progression in adults with HIV who are
      ineligible for initiation of antiretroviral treatment (the HEAT study): a multi
      site, randomised trial.
AB  - BACKGROUND: Co-infection with HIV and helminths is common in sub-Saharan Africa
      and findings from previous studies have suggested that anthelmintic treatment
      might delay immunosuppression in people with HIV. We aimed to assess the efficacy
      of empiric deworming of adults with HIV in delaying HIV disease progression.
      METHODS: In this non-blinded randomised trial, we enrolled adults (aged >=18
      years) with HIV who did not meet criteria for the initiation of antiretroviral
      treatment from three sites in Kenya. Using a computer-generated sequence, we
      randomly assigned (1:1) eligible participants to either empiric albendazole every
      3 months plus praziquantel annually (treatment group) or to standard care
      (control group). Participants were followed up for 24 months. We measured CD4
      cell counts every 6 months and plasma HIV RNA annually. The primary endpoints
      were a CD4 count of less than 350 cells per MUL and a composite endpoint
      consisting of the first occurrence of a CD4 count of less than 350 cells per MUL,
      first reported use of antiretroviral treatment, and non-traumatic deaths. We
      compared these measures by use of Cox proportional hazards regression and Kaplan
      Meier survival analyses. Primary analysis was done by intention to treat. The
      trial was registered with ClinicalTrials.gov, number NCT0050722. FINDINGS:
      Between Feb 6, 2008, and June 21, 2011, we enrolled and followed-up 948
      participants; 469 were allocated to the treatment group and 479 to the control
      group. All participants were provided with co-trimoxazole prophylaxis. Median
      baseline CD4 cell counts and HIV RNA concentrations did not differ between
      groups. We recorded no statistically significant difference between the treatment
      and control groups in the number of people reaching a CD4 count of fewer than 350
      cells per MUL (41.6 events per 100 person-years vs 46.2 events per 100 person
      years; hazard ratio 0.89, 95% CI 0.75-1.06, p=0.2) or the composite endpoint
      (44.0 events per 100 person-years vs 49.8 events per 100 person-years; 0.88, 0.74
      1.04, p=0.1). Serious adverse events, none of which thought to be treatment
      related, occurred at a similar frequency in both groups. INTERPRETATION: Our
      findings do not suggest an effect of empiric deworming in the delaying of HIV
      disease progression in adults with HIV in an area where helminth infection is
      common. Alternative approaches are needed to delay HIV disease progression in
      areas where co-infections are common.

PMID- 22971325
TI  - RCDA: a highly sensitive and specific alternatively spliced transcript assembly
      tool featuring upstream consecutive exon structures.
AB  - When applied to complex transcript datasets, current tools for automated assembly
      of mRNA sequences require long run times and produce exponentially increasing
      numbers of splice variants. Here, we describe RCDA, a genome-based transcript
      assembly tool comprising RCluster, that recursively clusters transcripts, and
      DAssemble, that generates composite transcript sequences through path-finding
      using a directed acyclic graph. Each exon included in a final transcript is
      associated with an array of all upstream consecutive exon structures obtained
      from original transcripts. When a depth-first-search path reaches an exon, the
      path is retained only if it contains a structure from that exon's array. RCDA
      assemblies, therefore, include only those transcripts with experimentally
      supported exon patterns. When applied to >23,000 transcripts from human
      chromosome 21, using biologically reasonable filters, RCDA execution time was
      approximately 4h. RCDA outperformed ECgene in reconstructing RefSeq transcripts
      and in limiting the total number of transcripts and transcripts per gene.

PMID- 22971326
TI  - Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning
      from Spain, August 2012.
AB  - Two Dutch travellers were infected with oseltamivir-resistant influenza
      A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August
      2012. Both cases were probably infected during separate holidays at the
      Catalonian coast (Spain). No epidemiological connection between the two cases was
      found, and neither of them was treated with oseltamivir before specimen
      collection. Genetic analysis of the neuraminidase gene revealed the presence of
      previously described permissive mutations that may increase the likelihood of
      such strains emerging and spreading widely.

PMID- 22971328
TI  - Clinical and virological findings in the ongoing outbreak of West Nile virus
      Livenza strain in northern Italy, July to September 2012.
AB  - In July-September 2012, one month earlier than in previous years, 13 confirmed
      human cases of West Nile virus infection were diagnosed in northern Italy,
      including five with neuroinvasive disease, three with West Nile fever, and five
      West Nile virus (WNV)-positive blood donors. In nine cases, the presence of the
      WNV lineage 1a Livenza strain, characterised in 2011, was ascertained.
      Symptomatic patients had prolonged viruria with high viral load.

PMID- 22971327
TI  - Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia
      in Germany.
AB  - We report the first culture-proven case of invasive aspergillosis (IA) caused by
      azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia
      in Germany. IA presented as breakthrough infection under posaconazole
      prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation
      in the cyp51A gene, which indicates an environmental origin of the strain. This
      case underscores the need for monitoring azole resistance in Aspergillus spp. and
      for routine susceptibility testing of moulds.

PMID- 22971329
TI  - Community cluster of meningococcal disease by Neisseria meningitidis serogroup C
      in Andalusia, Spain, March to May 2011.
AB  - Between March and May of 2011, a cluster of three fatal cases of meningococcal
      sepsis occurred in Andalusia, Spain, in a municipality with a population of
      around 20,000 inhabitants. The cases were in their mid-teens to early thirties
      and were notified to the epidemiological surveillance system of Andalusia
      (Sistema de Vigilancia Epidemiologica de Andalucia, SVEA) during a 68-day period
      from March through May 2011. All three were infected with the same strain of
      Neisseria meningitidis serogroup C genosubtype VR1:5-1;VR2:10-8. None of the
      cases had been previously vaccinated against N. meningitidis serogroup C.
      Antibiotic post-exposure chemoprophylaxis was administered to close contacts of
      every diagnosed case. Once the cluster was confirmed, the local population was
      informed through the media about the control measures taken by the health
      authorities. The vaccination history against N. meningitidis serogroup C of the
      population under 25 years-old in the municipality was checked. Vaccination was
      offered to unimmunised individuals younger than 25 years of age and an additional
      dose of vaccine was offered to those who had been vaccinated between 2000 and
      2006 with a vaccination schedule of three doses before the first year of age. No
      further cases occurred since the beginning of these actions.

PMID- 22971331
TI  - ECDC guidelines for the surveillance of invasive mosquitoes in Europe.

PMID- 22971330
TI  - A report on the large measles outbreak in Lyon, France, 2010 to 2011.
AB  - In 2010 and 2011, the city of Lyon, located in the Rhone-Alpes region (France),
      has experienced one of the highest incidences of measles in Europe. We describe a
      measles outbreak in the Lyon area, where cases were diagnosed at Lyon University
      hospitals (LUH) between 2010 and mid-2011. Data were collected from the mandatory
      notification system of the regional public health agency, and from the virology
      department of the LUH. All patients and healthcare workers who had contracted
      measles were included. Overall, 407 cases were diagnosed, with children of less
      than one year of age accounting for the highest proportion (n=129, 32%), followed
      by individuals between 17 and 29 years-old (n=126, 31%). Of the total cases, 72
      (18%) had complications. The proportions of patients and healthcare workers who
      were not immune to measles were higher among those aged up to 30 years.
      Consequently, women of childbearing age constituted a specific population at high
      risk to contract measles and during this outbreak, 13 cases of measles, seven
      under 30 years-old, were identified among pregnant women. This study highlights
      the importance of being vaccinated with two doses of measles vaccine, the only
      measure which could prevent and allow elimination of the disease.

PMID- 22971333
TI  - Doppler resistive index to reflect regulation of renal vascular tone during
      sepsis and acute kidney injury.
AB  - INTRODUCTION: Renal resistive index (RI), determined by Doppler ultrasonography,
      directly reveals and quantifies modifications in renal vascular resistance. The
      aim of this study was to evaluate if mean arterial pressure (MAP) is determinant
      of renal RI in septic, critically ill patients suffering or not from acute kidney
      injury (AKI). METHODS: This prospective observational study included 96 patients.
      AKI was defined according to RIFLE criteria and transient or persistent AKI
      according to renal recovery within 3 days. RESULTS: Median renal RIs were 0.72
      (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P
      = 0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in
      persistent AKI (P = 0.84). RI did not differ in patients given norepinephrine
      infusion and was not correlated with norepinephrine dose. RI was correlated with
      MAP (rho = -0.47; P = 0.002), PaO2/FiO2 ratio (rho = -0.33; P = 0.04) and age
      (rho = 0.35; P = 0.015) only in patients without AKI. CONCLUSIONS: A poor
      correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic
      and critically ill patients without AKI compared to patients with AKI. These
      findings suggest that determinants of RI are multiple. Renal circulatory response
      to sepsis estimated by Doppler ultrasonography cannot reliably be predicted
      simply from changes in systemic hemodynamics. As many factors influence its
      value, the interest in a single RI measurement at ICU admission to determine
      optimal MAP remains uncertain.

PMID- 22971335
TI  - Sphingosine-1-phosphate receptors as emerging targets for treatment of pain.
AB  - Lysolipids are important mediators of cellular communication in multiple
      physiological processes. Sphingosine-1-phosphate (S1P) is a major lysolipid in
      many organs, including the central nervous system (CNS). This commentary
      discusses recent findings on the role of S1P in regulating pain perception, and
      highlights advances and challenges in the field. S1P interacts with multiple
      cellular targets, including G-protein-coupled receptors. Known S1P receptors
      include five types, four of which are expressed in the CNS (S1P(1,2,3,5)) where
      they are localized on neurons and glia. S1P receptor-mediated G-protein
      activation has been demonstrated throughout the CNS, including regions that
      regulate nociception. S1P receptors couple to multiple G-proteins to produce
      various intracellular responses, and can mediate both excitatory and inhibitory
      neuromodulation, depending on the receptor type and cellular context. Both
      antinociceptive and pro-nociceptive effects of S1P have been reported, and both
      actions can involve S1P(1) receptors. Current evidence suggests that
      antinociception is mediated by CNS neurons, whereas pro-nociception is mediated
      by primary afferent neurons or immune cells in the periphery, or CNS glia.
      Nonetheless, peripheral administration of the S1P(1,3,4,5) agonist pro-drug,
      FTY720, produces antinociception. FTY720 is approved to treat multiple sclerosis,
      and produces potent anti-inflammatory effects, which suggests potential utility
      for painful autoimmune diseases. Furthermore, evidence suggests that the S1P
      system interacts with other pain-modulatory systems, such as endogenous
      cannabinoid and opioid systems, and putative novel sphingolipid targets in the
      CNS. These findings suggest that drugs targeting the S1P system could be
      developed as novel analgesics, either as monotherapy or potential adjuncts to
      established analgesics.

PMID- 22971334
TI  - NAAG peptidase inhibition in the periaqueductal gray and rostral ventromedial
      medulla reduces flinching in the formalin model of inflammation.
AB  - BACKGROUND: Metabotropic glutamate receptors (mGluRs) have been identified as
      significant analgesic targets. Systemic treatments with inhibitors of the enzymes
      that inactivate the peptide transmitter N-acetylaspartylglutamate (NAAG), an
      mGluR3 agonist, have an analgesia-like effect in rat models of inflammatory and
      neuropathic pain. The goal of this study was to begin defining locations within
      the central pain pathway at which NAAG activation of its receptor mediates this
      effect. RESULTS: NAAG immunoreactivity was found in neurons in two brain regions
      that mediate nociceptive processing, the periaqueductal gray (PAG) and the
      rostral ventromedial medulla (RVM). Microinjection of the NAAG peptidase
      inhibitor ZJ43 into the PAG contralateral, but not ipsilateral, to the formalin
      injected footpad reduced the rapid and slow phases of the nociceptive response in
      a dose-dependent manner. ZJ43 injected into the RVM also reduced the rapid and
      slow phase of the response. The group II mGluR antagonist LY341495 blocked these
      effects of ZJ43 on the PAG and RVM. NAAG peptidase inhibition in the PAG and RVM
      did not affect the thermal withdrawal response in the hot plate test. Footpad
      inflammation also induced a significant increase in glutamate release in the PAG.
      Systemic injection of ZJ43 increased NAAG levels in the PAG and RVM and blocked
      the inflammation-induced increase in glutamate release in the PAG. CONCLUSION:
      These data demonstrate a behavioral and neurochemical role for NAAG in the PAG
      and RVM in regulating the spinal motor response to inflammation and that NAAG
      peptidase inhibition has potential as an approach to treating inflammatory pain
      via either the ascending (PAG) and/or the descending pain pathways (PAG and RVM)
      that warrants further study.

PMID- 22971336
TI  - Protective immunity against iridovirus disease in mandarin fish, induced by
      recombinant major capsid protein of infectious spleen and kidney necrosis virus.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) is the causative agent of a
      disease causing high mortality and economic losses in mandarin fish, Siniperca
      chuatsi in China. But little information about vaccine development against ISKNV
      disease is available. In this study the gene encoding the major capsid protein
      (MCP), which is predominant structural component of the iridovirus particles, was
      cloned into a temperature induction prokaryotic expression vector pBV220 and a
      recombinant protein was detected about 50 kDa in molecular weight and accounted
      for 23% of total proteins of whole cell. Polyclonal antibodies were raised in
      rabbits against the purified protein and the reaction of the antibody was
      confirmed by western blotting using the purified protein and the spleen and
      kidney of healthy and diseased mandarin fish. The recombinant protein was
      renatured by dialysis and the juvenile mandarin fish were vaccinated by
      intraperitoneal injection with recombinant MCP emulsified with ISA 763 adjuvant
      at a dose of 20 MUg/fish, 50 MUg/fish and 100 MUg/fish, respectively. Specific
      antibodies and lymphocyte proliferation were detected in three groups and the
      values of MCP50 group were higher than the other two groups. After challenge
      infection with ISKNV, fish of MCP50 group showed significantly greater survival
      than the others and the RPS was 64.3%. In conclusion, the humoral immunity and
      cellar immunity of mandarin fish were induced by recombinant MCP and the best
      immune dose was 50 MUg/fish. To the best of our knowledge, this is the first time
      that a recombinant protein vaccine against ISKNV disease was developed in
      mandarin fish.

PMID- 22971337
TI  - Association between vitamin B12 intake and EURRECA's prioritized biomarkers of
      vitamin B12 in young populations: a systematic review.
AB  - OBJECTIVE: To review evidence on the associations between vitamin B12 intake and
      its biomarkers, vitamin B12 intake and its functional health outcomes, and
      vitamin B12 biomarkers and functional health outcomes. DESIGN: A systematic
      review was conducted by searching electronic databases, until January 2012, using
      a standardized strategy developed in the EURRECA network. Relevant articles were
      screened and sorted based on title and abstract, then based on full text, and
      finally included if they met inclusion criteria. A total of sixteen articles were
      included in the review. SETTING: Articles covered four continents: America (n 4),
      Europe (n 8), Africa (n 1) and Asia (n 3). SUBJECTS: Population groups included
      healthy infants, children and adolescents, and pregnant and lactating women.
      RESULTS: From the total number of 5815 papers retrieved from the initial search,
      only sixteen were eligible according to the inclusion criteria: five for infants,
      five for children and adolescents, and six for pregnant and lactating women.
      CONCLUSIONS: Only one main conclusion could be extracted from this scarce number
      of references: a positive association between vitamin B12 intake and serum
      vitamin B12 in the infant group. Other associations were not reported in the
      eligible papers or the results were not provided in a consistent manner. The low
      number of papers that could be included in our systematic review is probably due
      to the attention that is currently given to research on vitamin B12 in elderly
      people. Our observations in the current systematic review justify the idea of
      performing well-designed studies on vitamin B12 in young populations.

PMID- 22971338
TI  - Long-range interactions in nonsense-mediated mRNA decay are mediated by
      intrinsically disordered protein regions.
AB  - In nonsense-mediated mRNA decay (NMD), large protein complexes cooperate to
      trigger degradation of mRNA with a premature termination codon. Due to the
      extreme variation in the size and topology of its mRNA substrate, the structural
      underpinning of the fidelity of NMD is little understood. Based on bioinformatic
      predictions, we suggest that fly-casting mechanisms enabled by long disordered
      regions in NMD complexes are exploited for the underlying effective long-range
      communication.

PMID- 22971340
TI  - The tail nick augments Aeromonas sobria serine protease (ASP) activity in plasma
      through retarding inhibition by alpha2-macroglobulin.
AB  - ASP is a serine protease secreted by Aeromonas sobria, a sepsis-causing
      bacterium, and induces sepsis-mimicking disorders through plasma protein
      cleavage. The pathogen also secretes nASP that has a nick in the carboxy-terminal
      region. Compared with single-chain ASP (sASP), nASP had near-equivalent activity
      for small peptide substrates but was less proteolytic. Surprisingly, nASP cleaved
      proteins more in plasma and was inhibited by human alpha(2)-macroglobulin more
      slowly than sASP. Retarded inhibition by alpha(2)-macroglobulin allows nASP to
      keep proteolytic activity for longer in the host and exacerbate disorders at
      Aeromonas sobria infection sites. nASP may be an evolutional form to augment ASP
      virulence.

PMID- 22971339
TI  - Phosphatidylethanolamine and cardiolipin differentially affect the stability of
      mitochondrial respiratory chain supercomplexes.
AB  - The mitochondrial inner membrane contains two non-bilayer-forming phospholipids,
      phosphatidylethanolamine (PE) and cardiolipin (CL). Lack of CL leads to
      destabilization of respiratory chain supercomplexes, a reduced activity of
      cytochrome c oxidase, and a reduced inner membrane potential Deltapsi. Although
      PE is more abundant than CL in the mitochondrial inner membrane, its role in
      biogenesis and assembly of inner membrane complexes is unknown. We report that
      similar to the lack of CL, PE depletion resulted in a decrease of Deltapsi and
      thus in an impaired import of preproteins into and across the inner membrane. The
      respiratory capacity and in particular the activity of cytochrome c oxidase were
      impaired in PE-depleted mitochondria, leading to the decrease of Deltapsi. In
      contrast to depletion of CL, depletion of PE did not destabilize respiratory
      chain supercomplexes but favored the formation of larger supercomplexes
      (megacomplexes) between the cytochrome bc(1) complex and the cytochrome c
      oxidase. We conclude that both PE and CL are required for a full activity of the
      mitochondrial respiratory chain and the efficient generation of the inner
      membrane potential. The mechanisms, however, are different since these non
      bilayer-forming phospholipids exert opposite effects on the stability of
      respiratory chain supercomplexes.

PMID- 22971341
TI  - GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia.
AB  - BACKGROUND: Provoked vestibulodynia (PVD) is a pain disorder localized in the
      vestibular mucosa. It is the most common cause of dyspareunia among young women
      and it is associated with general pain hypersensitivity and other chronic pain
      conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene
      has been found to influence general pain sensitivity and the risk of developing a
      longstanding pain condition. The aim of this study was to investigate GCH1
      polymorphism in women with PVD and healthy controls, in correlation to pain
      sensitivity. RESULTS: We found no correlation between the previously defined pain
      protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation
      with pain sensitivity measured as pressure pain thresholds on the arm, leg and in
      the vestibule, coital pain scored on a visual analog scale and prevalence of
      other bodily pain conditions among women with PVD (n = 98) and healthy controls
      (n = 102). However, among patients with current treatment (n = 36), there was a
      significant interaction effect of GCH1-gene polymorphism and hormonal
      contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain
      thresholds on the arm (p = 0.04). PVD patients carrying the specified SNP
      combination and using HCs had higher pain sensitivity compared to non-carriers.
      In non-HC-users, carriers had lower pain sensitivity. CONCLUSIONS: The results of
      this study gave no support to the hypothesis that polymorphism in the GCH1-gene
      contributes to the etiology of PVD. However, among patients currently receiving
      treatment an interaction effect of the defined SNP combination and use of
      hormonal contraceptives on pain sensitivity was found. This finding offers a
      possible explanation to the clinically known fact that some PVD patients improve
      after cessation of hormonal contraceptives, indicating that PVD patients carrying
      the defined SNP combination of GCH1 would benefit from this intervention.

PMID- 22971342
TI  - Monocular myopic defocus and daily changes in axial length and choroidal
      thickness of human eyes.
AB  - Recent research indicates that brief periods (60 min) of monocular defocus lead
      to small but significant changes in human axial length. However, the effects of
      longer periods of defocus on the axial length of human eyes are unknown. We
      examined the influence of a 12 h period of monocular myopic defocus on the
      natural daily variations occurring in axial length and choroidal thickness of
      young adult emmetropes. A series of axial length and choroidal thickness
      measurements (collected at ~3 hourly intervals, with the first measurement at ~9
      am and the final measurement at ~9 pm) were obtained for 13 emmetropic young
      adults over three consecutive days. The natural daily rhythms (Day 1, baseline
      day, no defocus), the daily rhythms with monocular myopic defocus (Day 2, defocus
      day, +1.50 DS spectacle lens over the right eye), and the recovery from any
      defocus induced changes (Day 3, recovery day, no defocus) were all examined.
      Significant variations over the course of the day were observed in both axial
      length and choroidal thickness on each of the three measurement days (p <
      0.0001). The magnitude and timing of the daily variations in axial length and
      choroidal thickness were significantly altered with the monocular myopic defocus
      on day 2 (p < 0.0001). Following the introduction of monocular myopic defocus,
      the daily peak in axial length occurred approximately 6 h later, and the peak in
      choroidal thickness approximately 8.5 h earlier in the day compared to days 1 and
      3 (with no defocus). The mean amplitude (peak to trough) of change in axial
      length (0.030 +/- 0.012 on day 1, 0.020 +/- 0.010 on day 2 and 0.033 +/- 0.012 mm
      on day 3) and choroidal thickness (0.030 +/- 0.007 on day 1, 0.022 +/- 0.006 on
      day 2 and 0.027 +/- 0.009 mm on day 3) were also significantly different between
      the three days (both p < 0.05). The introduction of monocular myopic defocus
      disrupts the daily variations in axial length and choroidal thickness of human
      eyes (in terms of both amplitude and timing) that return to normal the following
      day after removal of the defocus.

PMID- 22971343
TI  - Distinct patterns of dysregulated expression of enzymes involved in androgen
      synthesis and metabolism in metastatic prostate cancer tumors.
AB  - Androgen receptor (AR) signaling persists in castration-resistant prostate
      carcinomas (CRPC), because of several mechanisms that include increased AR
      expression and intratumoral androgen metabolism. We investigated the mechanisms
      underlying aberrant expression of transcripts involved in androgen metabolism in
      CRPC. We compared gene expression profiles and DNA copy number alteration (CNA)
      data from 29 normal prostate tissue samples, 127 primary prostate carcinomas
      (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by
      quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor
      cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript
      levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and
      AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased.
      This aberrant expression was rarely associated with CNAs. Instead, our data
      suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition
      of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of
      the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In
      conclusion, our findings identify substantial interpatient heterogeneity and
      distinct patterns of dysregulated expression of enzymes involved in intratumoral
      androgen metabolism in PCa. These steroidogenic enzymes represent targets for
      complete suppression of systemic and intratumoral androgen levels, an objective
      that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A
      comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic
      blockade, and/or transcriptional repression of several steroidogenic enzymes, in
      combination with GnRH analogs and potent antiandrogens, would represent a
      powerful future strategy for PCa management.

PMID- 22971344
TI  - RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA
      damage.
AB  - Melanomas resist conventional chemotherapeutics, in part, through intrinsic
      disrespect of apoptotic checkpoint activation. In this study, using an unbiased
      genome-wide RNA interference screen, we identified RhoJ and its effector PAK1, as
      key modulators of melanoma cell sensitivity to DNA damage. We find that RhoJ
      activates PAK1 in response to drug-induced DNA damage, which then uncouples ATR
      from its downstream effectors, ultimately resulting in a blunted DNA damage
      response (DDR). In addition, ATR suppression leads to the decreased
      phosphorylation of ATF2 and consequent increased expression of the melanocyte
      survival gene Sox10 resulting in a higher DDR threshold required to engage
      melanoma cell death. In the setting of normal melanocyte behavior, this
      regulatory relationship may facilitate appropriate epidermal melanization in
      response to UV-induced DNA damage. However, pathologic pathway activation during
      oncogenic transformation produces a tumor that is intrinsically resistant to
      chemotherapy and has the propensity to accumulate additional mutations. These
      findings identify DNA damage agents and pharmacologic inhibitors of RhoJ/PAK1 as
      novel synergistic agents that can be used to treat melanomas that are resistant
      to conventional chemotherapies.

PMID- 22971345
TI  - Endoneurial macrophages induce perineural invasion of pancreatic cancer cells by
      secretion of GDNF and activation of RET tyrosine kinase receptor.
AB  - Perineural invasion of cancer cells (CPNI) is found in most patients with
      pancreatic adenocarcinomas (PDA), prostate, or head and neck cancers. These
      patients undergo palliative rather than curative treatment due to dissemination
      of cancer along nerves, well beyond the extent of any local invasion. Although
      CPNI is a common source of distant tumor spread and a cause of significant
      morbidity, its exact mechanism is undefined. Immunohistochemical analysis of
      specimens excised from patients with PDAs showed a significant increase in the
      number of endoneurial macrophages (EMPhi) that lie around nerves invaded by
      cancer compared with normal nerves. Video microscopy and time-lapse analysis
      revealed that EMPhis are recruited by the tumor cells in response to colony
      stimulated factor-1 secreted by invading cancer cells. Conditioned medium (CM) of
      tumor-activated EMPhis (tEMPhi) induced a 5-fold increase in migration of PDA
      cells compared with controls. Compared with resting EMPhis, tEMPhis secreted
      higher levels of glial-derived neurotrophic factor (GDNF), inducing
      phosphorylation of RET and downstream activation of extracellular signal
      regulated kinases (ERK) in PDA cells. Genetic and pharmacologic inhibition of the
      GDNF receptors GFRA1 and RET abrogated the migratory effect of EMPhi-CM and
      reduced ERK phosphorylation. In an in vivo CPNI model, CCR2-deficient mice that
      have reduced macrophage recruitment and activation showed minimal nerve invasion,
      whereas wild-type mice developed complete sciatic nerve paralysis due to massive
      CPNI. Taken together, our results identify a paracrine response between EMPhis
      and PDA cells that orchestrates the formation of cancer nerve invasion.

PMID- 22971347
TI  - Plasmodium chabaudi AS: distinct CD4(+)CD25(+)Foxp3(+) regulatory T cell
      responses during infection in DBA/2 and BALB/c mice.
AB  - Malaria infections display variation patterns of clinical course and outcome.
      Although CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play an essential role
      in immune homeostasis, the immune regulatory roles involved in malaria infection
      remains to be elucidated. Herein, we compared the disparity in Treg cells
      response during the course of blood stage Plasmodium chabaudi chabaudi AS (P. c
      chabaudi AS) infection in DBA/2 and BALB/c mice. BALB/c mice initiated a Th1/Th2
      profile respond to P. c chabaudi AS infection, but DBA/2 mice failed to control
      P. c chabaudi AS infection and almost of them died post-peak parasitemia. At the
      peak parasitemia, we found that higher proportion of Treg cells with elevated
      Foxp3 expression in DBA/2 than in BALB/c mice. We used anti-CD25 mAb to deplete
      Treg cells and found that the survival time and rate were prolonged in DBA/2 mice
      treated with anti-CD25 mAb. Treatment with anti-CD25 mAb in vivo led to enhanced
      pro-inflammation responses and Foxp3 expression decline on Treg cells. In
      contrast, after DBA/2 was treatment with anti-IL-10R mAb, IL-10R blockade in vivo
      caused excessive pro-inflammation responses and Foxp3 expression loss on
      CD4(+)CD25(+) T cells. Earlier death was found in all of DBA/2 mice with anti-IL
      10R mAb. It suggested that IL-2 and IL-10 signal involved in maintaining Foxp3
      expression on Treg cells. In all, the moderate suppressive activity of Treg cells
      may facilitate resistance to P. c chabaudi AS infection.

PMID- 22971346
TI  - Differential effects of polymorphic alleles of FGF receptor 4 on colon cancer
      growth and metastasis.
AB  - A gly(388)arg polymorphism (rs351855) in the transmembrane domain of the
      fibroblast growth factor receptor (FGFR4) is associated with increased risk,
      staging, and metastasis in several different types of cancer. To specifically
      assess the impact of the polymorphic FGFR4 in colorectal cancer (CRC), we
      engineered CRC cell lines with distinct endogenous expression patterns to
      overexpress either the FGFR4(gly) or FGFR4(arg) alleles. The biologic analyses
      revealed an oncogenic importance for both polymorphic alleles, but FGFR4(gly) was
      the stronger inducer of tumor growth, whereas FGFR4(arg) was the stronger inducer
      of migration. An evaluation of clinical specimens revealed that FGFR4 was
      upregulated in 20/71 patients independent of gly(388)arg status. There was no
      correlation between the presence of an FGFR4(arg) allele and CRC or polyp risk in
      3,471 participants of the CORSA study. However, among 182 patients with CRC,
      FGFR4(arg)-carriers had a fivefold higher risk of tumors that were stage II or
      greater. Together, our results established that both allelic forms of FGFR4 exert
      an oncogenic impact and may serve equally well as therapeutic targets in CRC. One
      important implication of our findings is that FGFR4(arg)-carriers are at a higher
      risk for more aggressive tumors and therefore may profit from early detection
      measures.

PMID- 22971349
TI  - Insights from the evaluation of a provincial healthy eating strategy in Nova
      Scotia, Canada.
AB  - OBJECTIVE: Healthy Eating Nova Scotia represents the first provincial
      comprehensive healthy eating strategy in Canada and a strategy that is framed
      within a population-health model. Five years after strategy launch, our objective
      was to evaluate Healthy Eating Nova Scotia to determine perceptions of strategy
      implementation and strategy outputs. The focus of the current paper is on the
      findings of this evaluation. DESIGN: We conducted an evaluation of the strategy
      through three activities that included a document review, survey of key
      stakeholders and in-depth interviews with key strategy informants. The findings
      from each of the activities were integrated to determine what has worked well
      with strategy implementation, what could be improved and what outputs have
      resulted. SETTING: The evaluation was conducted in the Canadian province of Nova
      Scotia. PARTICIPANTS: Participants for this evaluation included survey
      respondents (n 120) and key informants (n 16). A total of 156 documents were also
      reviewed. RESULTS: Significant investments have been made towards inter-sectoral
      partnerships and resourcing that has provided the necessary leadership and
      momentum for the strategy. Policy development has been leveraged through the
      strategy primarily in the health and education sectors and is perceived as a
      visible success. Clarity of human resource roles and funding within the context
      of a provincial strategy may be beneficial for continued strategy implementation,
      as is expansion of policy development. CONCLUSIONS: Known to be the first
      evaluation of its kind, these findings and related considerations will be of
      interest to policy makers developing and implementing similar strategies in their
      own jurisdictions.

PMID- 22971348
TI  - Norepinephrine regulates prophenoloxidase system-related parameters and gene
      expressions via alpha- and beta-adrenergic receptors in Litopenaeus vannamei.
AB  - The total (THC) and differential haemocyte counts (DHC), phenoloxidase (PO)
      activity, and prophenoloxidase (proPO) system-related genes were investigated in
      haemocytes of Litopenaeus vannamei that received saline, norepinephrine (NE), and
      NE co-treated with various adrenergic receptor (AR) antagonists both in vivo and
      in vitro. Results showed that semi-granular and granular cells of shrimp which
      received NE, NE + phentolamine (Phe), NE + prazosin (Pra), NE + propanolol (Pro)
      and NE + metoprolol (Met) significantly decreased, while the PO activity of the
      shrimp received NE + Phe in vivo was significant higher than all the other
      treatments. PO activities of haemocytes exposed to saline, Pra + NE, and Met + NE
      were significantly higher than those of haemocytes exposed to NE, Phe + NE, and
      Pro + NE in vitro. Similar phenomena in lipopolysaccharide- and beta-1,3-glucan
      binding protein (LGBP), proPO-I, proPO-II, serine proteinases (SP), and
      peroxinectin (PE) messenger (m)RNA expressions of haemocytes exposed to saline,
      NE, and NE co-treated with various AR antagonists were observed both in vivo and
      in vitro. No significant differences were observed for LGBP and proPO-II mRNA
      expressions between haemocytes treated with saline and Pra + NE, for proPO-I mRNA
      expression between haemocytes treated with saline and Met + NE; or for SP and PE
      mRNA expressions among haemocytes treated with saline, Pra + NE, and Met + NE.
      These results suggest that stress-induced NE may promote the migration of
      circulating granulocytes to the site of the injection and the existing proPO mRNA
      translation which had been stored in granulocytes. NE downregulated the LGBP,
      proPO-I, proPO-II, SP, and PE gene transcription by haemocytes via alpha1-, beta1
      , alpha1-, alpha1- and beta1-, and alpha1- and beta1-ARs, respectively, which
      subsequently decreased the PO activity by alpha1- and beta1-ARs in haemocytes of
      L. vannamei.

PMID- 22971350
TI  - Epigenetic modifications and mRNA levels of the imprinted gene Grb10 in serially
      passaged fibroblast cells.
AB  - The imprinted gene Grb10 influences fetal growth, adult behavior and tumor
      formation. Investigating this gene often involves consecutive passaging of cells
      in vitro. We analyzed changes in Grb10 DNA methylation and histone modifications
      in serially passaged adult mouse tail-tip fibroblast cells with bisulfite genomic
      sequencing method and chromatin immunoprecipitation (ChIP) respectively. There
      was a significant reduction in global DNA methylation, but no changes in
      methylation at CpG island 1 (CGI1) of Grb10. There were no changes in methylation
      at histone H3K4me2, but less methylated histone H3K27me3 was detected, along with
      more of the acetylated histones H3Ac and H4Ac. The major-type transcript level of
      Grb10 in fibroblasts increased mildly after extended cultivation. These results
      suggest consecutive passaging may affect epigenetic modifications of Grb10 in
      adult fibroblast cells.

PMID- 22971351
TI  - Development and validation of an automated system for detection and assessment of
      scratching in the rodent.
AB  - Pruritus, the sensation of itch, which evokes reflex scratching behavior, has a
      diverse etiology. Because of its clinical significance, mechanisms of
      pruriception are an important topic. In the present work we describe and validate
      a paw motion detector (PMD) system. The system employs a small removable metal
      band placed on one hind paw that provides a signal indicative of paw movement
      through perturbation of an electromagnetic (EM) field. C57Bl/6 mice were fitted
      with a unilateral hind paw band and adapted to testing cylinders equipped with EM
      signal emission and detection. The following observations were made: (1) in mice,
      unilateral SQ injection of 48/80 into the dorsolateral aspect of the neck evoked
      periodic high frequency bursts of scratching at the injected site with the
      ipsilateral (banded) but not the contralateral (not banded) hind paw. (2) Cross
      correlation between PMD and human observer counts after SQ 48/80 using the
      specified computational algorithm revealed a highly significant correlation. (3)
      SQ histamine and 48/80 over a 1hour interval produced dose dependent scratching,
      which diphenhydramine dose dependently reversed. Chloroquine scratching displayed
      an inverse u-shaped dose response curve, which was insensitive to
      diphenhydramine. (4) SQ 48/80 at intervals over 28 days showed no change in the
      scratching response within the same cohort of mice. (5) Power analysis showed 40%
      changes in scratching activity could be detected at the p<0.05 level with groups
      of 4 mice. These observations indicate that the system described can efficiently
      define the actions and pharmacology of pruritogenic agents.

PMID- 22971352
TI  - Variability of acute extracellular action potential measurements with multisite
      silicon probes.
AB  - Device miniaturization technologies have led to significant advances in sensors
      for extracellular measurements of electrical activity in the brain. Multisite,
      silicon-based probes containing implantable electrode arrays afford greater
      coverage of neuronal activity than single electrodes and therefore potentially
      offer a more complete view of how neuronal ensembles encode information. However,
      scaling up the number of sites is not sufficient to ensure capture of multiple
      neurons, as action potential signals from extracellular electrodes may vary due
      to numerous factors. In order to understand the large-scale recording
      capabilities and potential limitations of multisite probes, it is important to
      quantify this variability, and to determine whether certain key device parameters
      influence the recordings. Here we investigate the effect of four parameters,
      namely, electrode surface, width of the structural support shafts, shaft number,
      and position of the recording site relative to the shaft tip. This study employs
      acutely implanted silicon probes containing up to 64 recording sites, whose
      performance is evaluated by the metrics of noise, spike amplitude, and spike
      detection probability. On average, we find no significant effect of device
      geometry on spike amplitude and detection probability but we find significant
      differences among individual experiments, with the likelihood of detecting spikes
      varying by a factor of approximately three across trials.

PMID- 22971353
TI  - A glass-coated tungsten microelectrode enclosing optical fibers for optogenetic
      exploration in primate deep brain structures.
AB  - The optogenetic approach to primate brain circuitry has unparalleled potential
      for uncovering genetically and temporally resolved neuronal mechanisms of higher
      brain functions. In order to optogenetically investigate the large and complex
      primate brain, an optical-/electrical probe, or "optrode", must be inserted
      deeply, which requires the optrode to be not only long and stiff, but also sharp
      and smooth to reduce possible tissue damage. This study presents a tungsten
      microelectrode-based optrode that encloses optical fibers within its insulation
      glass. Optical fibers and a tungsten wire were tightly bound to each other and
      integrally coated with a smooth, thin layer of glass. This design satisfied the
      structural requirements for use in deep brain structures. The performance of the
      optrode was then examined in the thalamus of the rat and macaque monkeys which
      were injected with lentiviral vectors carrying the channelrhodopsin-2-enhanced
      yellow fluorescent protein (ChR2-EYFP) transgene. With fluorescence measurements
      via the optical fiber, ChR2-EYFP expression was detected clearly in vivo, which
      was confirmed by histological analysis in the rat. With photostimulation and
      extracellular recording, photo-responsive single-unit activities were isolated in
      the monkeys. The depth distribution of these units and the peak of the EYFP
      fluorescence profile overlapped consistently with each other. Thus, by developing
      a new probe, optogenetic methodology was successfully applied to a primate
      subcortical structure. This smooth glass-coated optrode is a promising tool for
      chronic in vivo experiments with various research targets including deep brain
      structures in behaving monkeys.

PMID- 22971354
TI  - A buffered form of creatine does not promote greater changes in muscle creatine
      content, body composition, or training adaptations than creatine monohydrate.
AB  - BACKGROUND: Creatine monohydrate (CrM) has been consistently reported to increase
      muscle creatine content and improve high-intensity exercise capacity. However, a
      number of different forms of creatine have been purported to be more efficacious
      than CrM. The purpose of this study was to determine if a buffered creatine
      monohydrate (KA) that has been purported to promote greater creatine retention
      and training adaptations with fewer side effects at lower doses is more
      efficacious than CrM supplementation in resistance-trained individuals. METHODS:
      In a double-blind manner, 36 resistance-trained participants (20.2 +/- 2 years,
      181 +/- 7 cm, 82.1 +/- 12 kg, and 14.7 +/- 5% body fat) were randomly assigned to
      supplement their diet with CrM (Creapure(r) AlzChem AG, Trostberg, Germany) at
      normal loading (4 x 5 g/d for 7-days) and maintenance (5 g/d for 21-days) doses;
      KA (Kre-Alkalyn(r), All American Pharmaceutical, Billings, MT, USA) at
      manufacturer's recommended doses (KA-L, 1.5 g/d for 28-days); or, KA with
      equivalent loading (4 x 5 g/d for 7-days) and maintenance (5 g/d) doses of CrM
      (KA-H). Participants were asked to maintain their current training programs and
      record all workouts. Muscle biopsies from the vastus lateralis, fasting blood
      samples, body weight, DEXA determined body composition, and Wingate Anaerobic
      Capacity (WAC) tests were performed at 0, 7, and 28-days while 1RM strength tests
      were performed at 0 and 28-days. Data were analyzed by a repeated measures
      multivariate analysis of variance (MANOVA) and are presented as mean +/- SD
      changes from baseline after 7 and 28-days, respectively. RESULTS: Muscle free
      creatine content obtained in a subgroup of 25 participants increased in all
      groups over time (1.4 +/- 20.7 and 11.9 +/- 24.0 mmol/kg DW, p = 0.03) after 7
      and 28-days, respectively, with no significant differences among groups (KA-L 
      7.9 +/- 22.3, 4.7 +/- 27.0; KA-H 1.0 +/- 12.8, 9.1 +/- 23.2; CrM 11.3 +/- 23.9,
      22.3 +/- 21.0 mmol/kg DW, p = 0.46). However, while no overall group differences
      were observed (p = 0.14), pairwise comparison between the KA-L and CrM groups
      revealed that changes in muscle creatine content tended to be greater in the CrM
      group (KA-L -1.1 +/- 4.3, CrM 11.2 +/- 4.3 mmol/kg DW, p = 0.053 [mean +/- SEM]).
      Although some significant time effects were observed, no significant group x time
      interactions (p > 0.05) were observed in changes in body mass, fat free mass, fat
      mass, percent body fat, or total body water; bench press and leg press 1RM
      strength; WAC mean power, peak power, or total work; serum blood lipids, markers
      of catabolism and bone status, and serum electrolyte status; or, whole blood
      makers of lymphocytes and red cells. Serum creatinine levels increased in all
      groups (p < 0.001) with higher doses of creatine promoting greater increases in
      serum creatinine (p = 0.03) but the increases observed (0.1 - 0.2 mg/dl) were
      well within normal values for active individuals (i.e., <1.28 +/- 0.2 mg/dl).
      Serum LDL was decreased to a greater degree following ingesting loading doses in
      the CrM group but returned to baseline during the maintenance phase. No side
      effects were reported. CONCLUSIONS: Neither manufacturers recommended doses of KA
      (1.5 g/d) or KA with equivalent loading (20 g/d for 7-days) and maintenance doses
      (5 g/d for 21-days) of CrM promoted greater changes in muscle creatine content,
      body composition, strength, or anaerobic capacity than CrM (20 g/d for 7-days, 5
      g/d for 21-days). There was no evidence that supplementing the diet with a
      buffered form of creatine resulted in fewer side effects than CrM. These findings
      do not support claims that consuming a buffered form of creatine is a more
      efficacious and/or safer form of creatine to consume than creatine monohydrate.

PMID- 22971355
TI  - Socio-economic inequalities in malnutrition among children and adolescents in
      Colombia: the role of individual-, household- and community-level
      characteristics.
AB  - OBJECTIVE: To examine socio-economic inequalities in malnutrition among Colombian
      children and adolescents, and to assess the contribution of individual-,
      household- and community-level factors to those inequalities. DESIGN: Cross
      sectional data were used from two sources: 2005 Colombian Demographic and Health
      Survey and 2005 Colombian census. Malnutrition outcomes included stunting and
      overweight. Multilevel Poisson models were used to estimate the association
      between individual, household and contextual characteristics and malnutrition.
      Changes in prevalence ratios of the poorest quintile (v. richest) were compared
      to assess the contribution of different characteristics to inequalities in
      malnutrition. SETTING: Population-based, representative of Colombia. SUBJECTS:
      Children and adolescents <18 years of age (n 30 779) from the Colombian
      Demographic and Health Survey. RESULTS: Children and adolescents living in the
      poorest households were close to five times more likely to be stunted, while
      those from the richest households were 1.3-2.8 times more likely than their
      poorest counterparts to be overweight. Care practices and household
      characteristics, particularly mother's education, explained over one-third of
      socio-economic inequalities in stunting. The proportion explained by access to
      services was not negligible (between 6% and 14 %). Access to sanitation was
      significantly associated with a lower prevalence of stunting for all age groups.
      Between 14% and 32% of socio-economic disparities in overweight were explained by
      maternal and household characteristics. Mother's overweight was positively
      associated with overweight of the child. CONCLUSION: Socio-economic inequalities
      in stunting and overweight coexist among children and adolescents in Colombia.
      Malnutrition inequalities are largely explained by household characteristics,
      suggesting the need for targeted interventions.

PMID- 22971357
TI  - Urine metabolomics.
AB  - Metabolomics is a powerful technique for the discovery of novel biomarkers and
      elucidation of biochemical pathways to improve diagnosis, prognosis and therapy.
      An advantage of this approach is its ability to assess global metabolic profiles
      to enhance pathologic characterization. Urine is an ideal bio-medium for disease
      study because it is readily available, easily obtained and less complex than
      other body fluids. Ease of collection allows for serial sampling to monitor
      disease and therapeutic response. Because of this potential, this paper will
      review urine metabolomic analysis, discuss its significance in the post-genomic
      era and highlight the specific roles of endogenous small molecule metabolites in
      this emerging field.

PMID- 22971358
TI  - Sociodemographic characteristics and food habits of organic consumers--a study
      from the Danish National Birth Cohort.
AB  - OBJECTIVE: To develop a basis for building models that can examine the impact of
      organic food (OF) choices on maternal and offspring health, including
      identification of factors associated with OF consumption and underlying dietary
      patterns. DESIGN: Dietary intake was collected for the preceding month from an
      FFQ in mid-pregnancy and information on sociodemographic characteristics was
      collected from telephone interviews during pregnancy. From a question about OF
      consumption in the FFQ, including six food categories, an OF preference index was
      calculated. Latent variables that captured the variability in OF choices in
      relation to dietary intake were defined. SETTING: The Danish National Birth
      Cohort (DNBC), 1996-2002. SUBJECTS: Pregnant women from DNBC (n 60,773). RESULTS:
      We found that frequent OF use was highly associated with age, occupational
      status, urbanization, smoking and vegetarianism. By principal components analysis
      we identified two eating patterns, a 'Western dietary pattern' and a 'Prudent
      dietary pattern', that explained 14.2% of the variability in data. Frequent OF
      users consumed a more 'prudent' diet compared with non-users and had
      significantly higher intakes of vegetables (167%), fibre (113%) and n-3 fatty
      acids (111%) and less saturated fat (28%). CONCLUSIONS: Frequent OF users seemed
      to have a healthier lifestyle than non-users. These findings highlight a major
      challenge in observational studies examining the impact of OF consumption on
      health due to potentially irremediable confounding factors.

PMID- 22971356
TI  - A cluster randomized controlled trial of the effectiveness and cost-effectiveness
      of intermediate care clinics for diabetes (ICCD): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2
      diabetes. In the United Kingdom, clinical care is primarily provided by general
      practitioners (GPs) rather than hospital specialists. Intermediate care clinics
      for diabetes (ICCD) potentially provide a model for supporting GPs in their care
      of people with poorly controlled type 2 diabetes and in their management of
      cardiovascular risk factors. This study aims to (1) compare patients with type 2
      diabetes registered with practices that have access to an ICCD service with those
      that have access only to usual hospital care; (2) assess the cost-effectiveness
      of the intervention; and (3) explore the views and experiences of patients,
      health professionals and other stakeholders. METHODS/DESIGN: This two-arm cluster
      randomized controlled trial (with integral economic evaluation and qualitative
      study) is set in general practices in three UK Primary Care Trusts. Practices are
      randomized to one of two groups with patients referred to either an ICCD
      (intervention) or to hospital care (control). Intervention group: GP practices in
      the intervention arm have the opportunity to refer patients to an ICCD - a
      multidisciplinary team led by a specialist nurse and a diabetologist. Patients
      are reviewed and managed in the ICCD for a short period with a goal of improving
      diabetes and cardiovascular risk factor control and are then referred back to
      practice. or CONTROL GROUP: Standard GP care, with referral to secondary care as
      required, but no access to ICCD. Participants are adults aged 18 years or older
      who have type 2 diabetes that is difficult for their GPs to control. The primary
      outcome is the proportion of participants reaching three risk factor targets:
      HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end
      of the 18-month intervention period. The main secondary outcomes are the
      proportion of participants reaching individual risk factor targets and the
      overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the
      United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary
      outcomes include body mass index and waist circumference, use of medication,
      reported smoking, emotional adjustment, patient satisfaction and views on
      continuity, costs and health related quality of life. We aimed to randomize 50
      practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been
      randomized, 1,997 patients have been recruited to the trial, and 20 patients have
      been recruited to the qualitative study. Results will be available late 2012.
      TRIAL REGISTRATION: [ClinicalTrials.gov: Identifier NCT00945204].

PMID- 22971359
TI  - Crustins from eyestalk cDNA library of swimming crab Portunus trituberculatus:
      molecular characterization, genomic organization and expression analysis.
AB  - Crustins are cationic, cysteine-rich antimicrobial proteins, containing a single
      whey acidic protein (WAP) domain in the C-terminal end. Different from the
      reported Ptcrustin in the hemocytes, two novel crustin genes (PtCrustin2 and
      PtCrustin3) were cloned completely from the eyestalk cDNA library of Portunus
      trituberculatus in this study. All PtCrustins share the consensus cysteine motif
      and are considered as Type I crustins. Four exons and three introns are
      identified in genomic DNA sequence of PtCrustin3 while three exons and two
      introns in PtCrustin2. The mRNA transcripts of PtCrustin2 and PtCrustin3 are
      mainly detected in eyestalk and gills, but not in hemocytes. Although both
      PtCrutins are up-regulated after challenge of three microorganisms, PtCrustin3
      seems to respond more quickly to microbial challenge than Ptcrustin2. Unlike most
      crustins, both recombinant PtCrustin2 and PtCrustin3 exhibit antibacterial
      activity against Gram-positive bacteria Micrococcus luteus and Staphyloccocus
      aureus and Gram-negative bacterium Pseudomonas aeruginosa. In addition,
      rPtCrustin2 is moderately active against yeast Pichia pastoris and rPtCrustin3
      show significant activity against Gram-negative bacterium Vibrio alginolyticus.
      These results indicate that PtCrustin2 and PtCrustin3 are two novel crustins and
      play different roles in immune response of P. trituberculatus against microbial
      challenge.

PMID- 22971360
TI  - The amygdala and the pedunculopontine tegmental nucleus: interactions controlling
      active (rapid eye movement) sleep.
AB  - There is a consensus that active sleep (AS; i.e., REM sleep) is produced by
      cholinergic projections from the pedunculopontine tegmental nuclei (PPT) that
      activate AS-on neurons in the nucleus pontis oralis (NPO) that are components of
      the AS-Generator. However, there is a growing body of evidence indicating that
      other sites, such as the amygdala, also participate in the control of AS by
      inducing the discharge of AS-Generator neurons. In this regard, we recently
      reported that there are direct, excitatory (glutamatergic) projections from the
      central nucleus of the amygdala (CNA) to presumptive AS-Generator neurons in the
      NPO. We therefore hypothesized that the CNA and the PPT act alone, as well as in
      concert, to promote AS. To test this hypothesis, the effects of stimulation of
      the CNA and the PPT on the activity of NPO neurons, recorded intracellularly,
      were examined in urethane-anesthetized rats. Stimulation of either the CNA or the
      PPT evoked short-latency excitatory postsynaptic potentials (EPSPs) in the same
      neurons within the NPO. The amplitude of PPT-evoked EPSPs that were recorded from
      NPO neurons increased by 20.1 to 58.6% when stimulation of the PPT was preceded
      by stimulation of the CNA at an interval of 0 to 12 ms: maximal potentiation
      occurred at an interval of 4 to 6 ms. Concurrent subthreshold stimulation of the
      CNA and the PPT resulted in the discharge of NPO neurons. NPO neurons that were
      activated following CNA and/or PPT stimulation were identified morphologically
      and found to be multipolar with diameters >20 MUm; similar neurons in the same
      NPO site have been previously identified as AS-Generator neurons. The present
      data demonstrate the presence of converging excitatory synaptic inputs from the
      CNA and the PPT that are capable of promoting the discharge of AS-Generator
      neurons in the NPO. Therefore, we suggest that the occurrence of AS depends upon
      interactions between cholinergic projections from the PPT and glutamatergic
      projections from the CNA as well as inputs from other sites that project to AS
      Generator neurons.

PMID- 22971362
TI  - Re: Cancers with increasing incidence trends in the United States: 1999 through
      2008.

PMID- 22971361
TI  - Re: Placement of marker coils at biopsy: usefulness in the localization of poorly
      visualized renal neoplasms for subsequent CT-guided radiofrequency ablation.

PMID- 22971363
TI  - Re: Cigarette smoking and renal cell carcinoma risk among black and white
      Americans: effect modification by hypertension and obesity.

PMID- 22971364
TI  - Re: Smoking knowledge assessment and cessation trends in patients with bladder
      cancer presenting to a tertiary referral center.

PMID- 22971365
TI  - Re: Screening for prostate cancer: U.S. Preventive Services Task Force
      recommendation statement.

PMID- 22971367
TI  - Re: The prostate cancer conundrum revisited: treatment changes and prostate
      cancer mortality declines.

PMID- 22971368
TI  - Re: Predictive value of MRI in the localization, staging, volume estimation,
      assessment of aggressiveness, and guidance of radiotherapy and biopsies in
      prostate cancer.

PMID- 22971369
TI  - Re: An analysis of whether higher health care spending in the United States
      versus Europe is 'worth it' in the case of cancer.

PMID- 22971370
TI  - Re: The clinical features and management of testicular germ cell tumours in
      patients aged 60 years and older.

PMID- 22971372
TI  - Re: A randomized trial of computer kiosk-expedited management of cystitis in the
      emergency department.

PMID- 22971373
TI  - Re: Cefpodoxime vs ciprofloxacin for short-course treatment of acute
      uncomplicated cystitis: a randomized trial.

PMID- 22971378
TI  - Re: Effect of early realignment on length and delayed repair of postpelvic
      fracture urethral injury.

PMID- 22971379
TI  - Re: Non-transecting anastomotic bulbar urethroplasty: a preliminary report. Re:
      The augmented nontransected anastomotic urethroplasty for the treatment of bulbar
      urethral strictures.

PMID- 22971380
TI  - Re: American Geriatrics Society updated Beers Criteria for potentially
      inappropriate medication use in older adults.

PMID- 22971381
TI  - Re: Inappropriate medication use in older adults undergoing surgery: a national
      study.

PMID- 22971382
TI  - Re: Accumulated frailty characteristics predict postoperative discharge
      institutionalization in the geriatric patient.

PMID- 22971383
TI  - Re: Outcomes in geriatric genitourinary trauma.

PMID- 22971384
TI  - Re: Urinary incontinence: an under-recognized risk factor for falls among elderly
      dementia patients.

PMID- 22971385
TI  - Re: Patients aged 80 and older undergoing orthopedic or urologic surgery: a
      prospective study focusing on perioperative morbidity and mortality.

PMID- 22971386
TI  - Re: Preservation solutions for static cold storage of kidney allografts: a
      systematic review and meta-analysis.

PMID- 22971387
TI  - Re: Defining cure.

PMID- 22971388
TI  - Re: Reducing nocturia in the elderly: a randomized placebo-controlled trial of
      staggered furosemide and desmopressin.

PMID- 22971389
TI  - Re: Incontinence improves in older women after intensive pelvic floor muscle
      training: an assessor-blinded randomized controlled trial.

PMID- 22971390
TI  - Re: Nocturia and quality of life: results from the Boston area community health
      survey.

PMID- 22971392
TI  - Re: Comparison of the clinical efficacy of medical treatment of symptomatic
      benign prostatic hyperplasia between normal and obese patients.

PMID- 22971391
TI  - Re: Lessons from a patient experience survey in a randomized surgical trial of
      treatment of stress urinary incontinence in women.

PMID- 22971393
TI  - Re: Comparison of Murraya koenigii- and Tribulus terrestris-based oral
      formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in
      men aged >50 years: a double-blind, double-dummy, randomized controlled trial.

PMID- 22971394
TI  - Re: Cost-effectiveness of combination therapy for treatment of benign prostatic
      hyperplasia: a model based on the findings of the Combination of Avodart and
      Tamsulosin trial.

PMID- 22971395
TI  - Re: What we don't talk about when we don't talk about sex(1): results of a
      national survey of U.S. obstetrician/gynecologists.

PMID- 22971396
TI  - Re: Depression in premenopausal women with HSDD: baseline findings from the HSDD
      Registry for Women.

PMID- 22971397
TI  - Re: Assessing couples' preferences for postoperative sexual rehabilitation before
      radical prostatectomy.

PMID- 22971398
TI  - Re: The relationship between pelvic organ prolapse, genital body image, and
      sexual health.

PMID- 22971399
TI  - Re: Demonstration of erectile management techniques to men scheduled for radical
      prostatectomy reduces long-term regret: a comparative cohort study.

PMID- 22971401
TI  - Re: Are there subtle genome-wide epigenetic alterations in normal offspring
      conceived by assisted reproductive technologies?

PMID- 22971400
TI  - Re: Epigenetics of the male gamete.

PMID- 22971402
TI  - Re: Are ICSI adolescents at risk for increased adiposity?

PMID- 22971403
TI  - Re: Food intake and social habits in male patients and its relationship to
      intracytoplasmic sperm injection outcomes.

PMID- 22971404
TI  - Re: Association between obesity and alteration of sperm DNA integrity and
      mitochondrial activity.

PMID- 22971406
TI  - Re: Current status of organ transplantation in Japan.

PMID- 22971407
TI  - Re: Current referral patterns and means to improve accuracy in diagnosis of
      undescended testis.

PMID- 22971409
TI  - Re: Risk factors for progressive deterioration of semen quality in patients with
      varicocele.

PMID- 22971411
TI  - Re: Familial testicular torsion in three consecutive generations of first-degree
      relatives.

PMID- 22971410
TI  - Re: Incomplete prenatal torsion of the testicle--a successful salvage.

PMID- 22971412
TI  - Re: Urine risk factors in children with calcium kidney stones and their siblings.

PMID- 22971414
TI  - Re: Collective and single cell behavior in epithelial contact inhibition.

PMID- 22971415
TI  - Re: Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets
      malignant cancer but not benign cells.

PMID- 22971416
TI  - Re: Three-dimensional cancer-bone metastasis model using ex-vivo co-cultures of
      live calvarial bones and cancer cells.

PMID- 22971417
TI  - Re: Percutaneous radiofrequency ablation of virtual tumours in canine kidney
      using global positioning system-like technology.

PMID- 22971418
TI  - Exciton-related nonlinear optical properties in cylindrical quantum dots with
      asymmetric axial potential: combined effects of hydrostatic pressure, intense
      laser field, and applied electric field.
AB  - : The exciton binding energy of an asymmetrical GaAs-Ga1-xAlxAs cylindrical
      quantum dot is studied with the use of the effective mass approximation and a
      variational calculation procedure. The influence on this quantity of the
      application of a direct-current electric field along the growth direction of the
      cylinder, together with that of an intense laser field, is particularly
      considered. The resulting states are used to calculate the exciton-related
      nonlinear optical absorption and optical rectification, whose corresponding
      resonant peaks are reported as functions of the external probes, the quantum dot
      dimensions, and the aluminum molar fraction in the potential barrier regions.

PMID- 22971419
TI  - Recurrent unexplained hyperammonemia in an adolescent with arginase deficiency.
AB  - OBJECTIVES: This report investigates the etiology of recurrent episodic
      elevations in plasma ammonia in an adolescent male with arginase deficiency as
      there were concerns regarding pre-analytical and analytical perturbations of
      ammonia measurements. There were repeated discrepancies between the magnitude of
      his ammonia levels and the severity of his clinical signs of hyperammonemia.
      PATIENT AND METHODS: The patient is a fourteen-year-old arginase-deficient male
      diagnosed at three years of age. Since 2008 (when he reached 10 years of age),
      there appeared to be an increase in the frequency of hospitalizations with
      elevated ammonia. A typical emergency visit with initial ammonia of 105 MUmol/L
      (reference interval: 16-47 MUmol/L) is illustrated. Pre-analytical and analytical
      procedures for the patient's sample handling were retrospectively examined. His
      ammonia levels were compiled since diagnosis. The frequency of his initial or
      peak ammonia levels greater than two times (94 MUmol/L) or four times (188
      MUmol/L) the upper limit of normal was computed. Student t-test was used to
      calculate the significance of the differences before 2008 and since 2008.
      RESULTS: One out of eleven and ten out of 19 hospitalizations had initial ammonia
      greater than two times normal before and after 2008, respectively. Both the
      patient's overall ammonia and peak ammonia levels are significantly higher since
      2008 (p value <0.001 for both) than those before 2008. CONCLUSIONS: To our
      knowledge, few adolescent males with arginase deficiency experience recurrent
      episodes of hyperammonemia requiring intravenous nitrogen scavenging agents. We
      hope that this study provides new insights into the natural history of arginase
      deficiency and the management of such patients.

PMID- 22971420
TI  - A tool to facilitate clinical biomarker studies--a tissue dictionary based on the
      Human Protein Atlas.
AB  - The complexity of tissue and the alterations that distinguish normal from cancer
      remain a challenge for translating results from tumor biological studies into
      clinical medicine. This has generated an unmet need to exploit the findings from
      studies based on cell lines and model organisms to develop, validate and
      clinically apply novel diagnostic, prognostic and treatment predictive markers.
      As one step to meet this challenge, the Human Protein Atlas project has been set
      up to produce antibodies towards human protein targets corresponding to all human
      protein coding genes and to map protein expression in normal human tissues,
      cancer and cells. Here, we present a dictionary based on microscopy images
      created as an amendment to the Human Protein Atlas. The aim of the dictionary is
      to facilitate the interpretation and use of the image-based data available in the
      Human Protein Atlas, but also to serve as a tool for training and understanding
      tissue histology, pathology and cell biology. The dictionary contains three main
      parts, normal tissues, cancer tissues and cells, and is based on high-resolution
      images at different magnifications of full tissue sections stained with H & E.
      The cell atlas is centered on immunofluorescence and confocal microscopy images,
      using different color channels to highlight the organelle structure of a cell.
      Here, we explain how this dictionary can be used as a tool to aid clinicians and
      scientists in understanding the use of tissue histology and cancer pathology in
      diagnostics and biomarker studies.

PMID- 22971421
TI  - Development of a rapid and inexpensive method to reveal natural antisense
      transcripts.
AB  - BACKGROUND: Natural antisense transcripts (NATs) are a group of RNAs encoded
      within a cell that have transcript complementarity to other RNA transcripts. NATs
      have been identified in multiple eukaryotes, including humans, mice, yeast and
      several plants, and are known to play crucial roles in gene regulation and
      modification via RNA interference, alternative splicing and genomic imprinting.
      NATs are also involved in several human diseases. RESULTS: We describe a novel
      method to detect the occurrence of target NATs in specific plant tissues. This
      method differs from the others currently used in molecular biology laboratories
      for a number of reasons, particularly the simplicity and versatility of
      application, low cost and lower material requirement. We demonstrate that NATs
      can be detected by using diluted cDNA, avoiding the need for a large amount of
      RNA, thus differing from basic techniques, such as Northern blot hybridisation
      and reverse-transcription PCR amplification. Furthermore, our method also allows
      the precise detection of long NATs and their cloning into plasmid vectors for
      downstream applications. We also reported the first case of a tissue-specific NAT
      occurring in Oleaceae family and, the antisense orientation of this transcript,
      allows the splicing of two introns otherwise impossible in the sense orientation.
      CONCLUSIONS: This method is the first that combines the polymerisation and
      cleavage activity of DNA polymerase and exonuclease enzymes, respectively, to
      discover NATs in living organisms. It may simplify the discovery of NATs in
      plants providing a new strategy for an easy identification and characterization
      of this group of RNA molecules. Furthermore, since NATs are found in multiple
      eukaryotes, our method can be easily applied to a wide range of organisms,
      including human, mice and yeast.

PMID- 22971423
TI  - Publishing survey research.

PMID- 22971422
TI  - Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation
      of adipose function.
AB  - G protein-coupled receptor 116 (GPR116) is a novel member of the G protein
      coupled receptors and its function is largely unknown. To investigate the
      physiological function of GPR116 in vivo, we generated adipose tissue specific
      conditional Gpr116 knockout mice (CKO) and fed them on standard chow or high fat
      diets. Selective deletion of Gpr116 in adipose tissue caused a pronounced glucose
      intolerance and insulin resistance in mice, especially when challenged with a
      high fat diet. Biochemical analysis revealed a more severe hepatosteatosis in CKO
      mice. Additionally, we found that CKO mice showed a lowered concentration of
      circulating adiponectin and an increased level of serum resistin. Our study
      suggests that GPR116 may play a critical role in controlling adipocyte biology
      and systemic energy homeostasis.

PMID- 22971424
TI  - Stage and age structured Aedes vexans and Culex pipiens (Diptera: Culicidae)
      climate-dependent matrix population model.
AB  - Aedes vexans and Culex pipiens mosquitoes are potential vectors of many
      arbovirial diseases. Due to the ongoing climate changes and reappearance of some
      zoonoses that were considered eradicated, there is a growing concern about
      potential disease outbreaks. Therefore, the prediction of increased adult
      population abundances becomes an essential tool for the appropriate
      implementation of mosquito control strategies. In order to describe the
      population dynamics of A. vexans and C. pipiens mosquitoes in temperate climate
      regions, a 3-year period (2008-2010) climate-dependent model was constructed. The
      models represent a combination of mathematical modeling and computer simulations,
      and include temperature, rainfall, photoperiods, and the flooding dynamics of A.
      vexans breeding sites. Both models are structured according to the developmental
      stages, and by individuals' "age" (i.e., time spent in each developmental stage),
      as we wanted to enable a time delay between the appearances of different
      developmental stages of mosquitoes. The time delay length is temperature
      dependent, with temperature being the most important factor influencing
      morphogenesis rates in immatures and gonotrophic cycle durations in adult
      mosquitoes. To determine which developmental stages are the most sensitive and
      are those at which control measures should be aimed, transient elasticities were
      calculated. The analysis showed that both mosquito species reacted to
      perturbation of the same matrix elements; however, in the C. pipiens model, the
      stage with greatest proportional sensitivity (i.e., elasticity) during most of
      the three-year reproduction season contained adults, while in the A. vexans model
      it contained larvae. The models were validated by comparing 7-day model outputs
      with data on human bait collection (HBC) obtained from the Public Health
      Institute of Osijek-Baranja, with both model outputs showing valid compatibility
      with field data over the three-year period. The proposed models can easily be
      modified to describe population dynamics of other mosquito species in different
      geographical areas, as well as for assessing the efficiency and optimization of
      different mosquito control strategies.

PMID- 22971425
TI  - [A man with progressive diplopia].
AB  - A 71-year-old man presented with progressive diplopia due to swelling of a
      Miragel explant. Removal of the explant resulted in relief of symptoms.

PMID- 22971426
TI  - [A young woman with progressive cerebral atrophy].
AB  - A 21-year-old patient suffering from neurofibromatosis type 1 had received
      radiotherapy for a chiasm glioma 17 years ago. Fourteen years later, there was
      progressive deterioration of several neurological functions. MRI scans showed a
      progressively increasing volume loss of the left hemisphere and stenoses around
      the circle of Willis with secondary parenchymal effects. Based on conventional
      cerebral angiography, the diagnosis 'moyamoya syndrome' was made.

PMID- 22971427
TI  - [A newborn with pustules].
AB  - A full-term afebrile male infant was born with multiple sterile pustules, which
      easily ruptured to reveal an underlying erythematous skin. He was diagnosed with
      'transient neonatal pustulosis', a benign self-limiting condition which
      disappears within a few days. However, hyperpigmented skin lesions (melanosis)
      may remain visible for several months.

PMID- 22971428
TI  - [How do patients interpret terms for medically unexplained symptoms?].
AB  - OBJECTIVE: To investigate how primary care patients interpret the existing
      terminology used to describe medically unexplained symptoms; to contribute to the
      current academic discussion on unequivocal terminology. DESIGN: Descriptive
      cohort study. METHODS: We approached patients in the waiting rooms of two general
      medical practices in the city of Groningen and in the province of Drenthe. Based
      on a fictitious case, the patients were asked to assign connotations to a number
      of possible diagnoses for medically unexplained tiredness. The patients could
      choose from seven predetermined connotations. Among the diagnoses for medically
      unexplained tiredness were 'functional fatigue', 'chronic fatigue syndrome',
      'psychosomatic tiredness', and 'medically unexplained tiredness'. From the seven
      connotations, we labeled three connotations as being negative. When patients gave
      at least one negative connotation to a possible diagnosis, the diagnosis was
      labeled as 'offensive'. RESULTS: A total of 184 patients participated in the
      study. From the alternative diagnoses for medically unexplained tiredness,
      'psychosomatic tiredness' had the most negative connotations: at least one
      negative connotation for 65 (35%) patients. 'Chronic fatigue syndrome' and
      'functional fatigue' had the fewest negative connotations: at least one negative
      connotation for respectively 17 (9%) and 24 (13%) patients. CONCLUSION: The terms
      'chronic fatigue syndrome' and 'functional fatigue' were less offensive. Our
      results could imply that terms for medically unexplained tiredness that refer
      less to a psychological basis are most acceptable for the patient.

PMID- 22971429
TI  - [Submucosal presentation of Whipple's disease: a variant that is easily missed].
AB  - Whipple's disease is a multisystem, and often chronic, disease caused by
      infection with the bacterium Tropheryma whipplei, and mainly occurs in middle
      aged Caucasian men. In most cases, histological detection of large numbers of
      bacteria-laden macrophages in the mucosa of the small intestine confirms the
      diagnosis. Less commonly, these macrophages may be sparse and predominantly
      located beneath the mucosa. In these submucosally presenting cases, endoscopic
      and classic histological clues are absent and, therefore, the diagnosis can be
      missed. As a result, further periodic acid-Schiff (PAS) staining and PCR analysis
      are of great importance in arriving at the correct diagnosis.

PMID- 22971432
TI  - [Revision of the practical guideline 'Treatment of chronic viral hepatitis B
      infection'].
AB  - This article contains our comments on the practical guideline for treating
      chronic hepatitis B in the Netherlands, which was published in 2008. Revision of
      this guideline had already become necessary in 2011 due to rapidly changing
      therapeutic strategies. New second-generation drugs show minimal antiviral
      resistance and their use should be considered more frequently. In addition,
      certified multidisciplinary centres of expertise should contribute to the
      improvement of care for patients with chronic hepatitis B. Our opinion is that
      the revisions make the guideline for treating chronic hepatitis B more complete
      and up to date.

PMID- 22971434
TI  - [Tailored breast cancer screening with ultrasound and MRI?].
AB  - The ACRIN 6666 trial has shown that the addition of ultrasound or MRI to
      mammography screening detects more breast cancers in women with dense breasts and
      at least one other breast cancer risk factor. This higher detection yield is
      accompanied by an increase in false-positive findings. Unfortunately, this study
      was not randomized into groups with and without the addition of ultrasound and
      MRI. It is therefore impossible to investigate if the improved detection rate
      also results in a smaller number of interval tumours which would be the best
      indication of the ultimate goal - a decrease in breast cancer mortality. Before
      any new and costly imaging is added to the breast cancer screening program, it is
      necessary to investigate if this will not merely increase the detection of
      indolent tumours. If additional imaging is implemented too hastily it will be
      hard to turn it back, and impossible to assess it in a randomized study.

PMID- 22971436
TI  - [Appropriate and inappropriate use of indwelling urinary catheters].
AB  - Many hospitalized patients receive a urinary catheter during their stay. In 21
      54% of patients, however, there is no appropriate indication for this. The most
      significant complication caused by the use of urinary catheters is the
      development of a urinary tract infection (UTI), one of the most common nosocomial
      infections. In 71-80% of hospital acquired UTIs a urinary catheter is present.
      The duration of the presence of a catheter is the major risk factor for catheter
      associated UTI. Reducing the number of inappropriate catheterisations is an
      effective way of preventing catheter-related UTIs. Inappropriate use of
      indwelling urinary catheters can be reduced by maintaining strict guidelines on
      justifiable indications for inserting a urinary catheter, verifying daily whether
      the indication still applies, and by timely removal of the catheter when it is
      not or no longer needed.

PMID- 22971438
TI  - Simple and efficient methods to generate split roots and grafted plants useful
      for long-distance signaling studies in Medicago truncatula and other small
      plants.
AB  - BACKGROUND: Long distance signaling is a common phenomenon in animal and plant
      development. In plants, lateral organs such as nodules and lateral roots are
      developmentally regulated by root-to-shoot and shoot-to-root long distance
      signaling. Grafting and split root experiments have been used in the past to
      study the systemic long distance effect of endogenous and environmental factors,
      however the potential of these techniques has not been fully realized because
      data replicates are often limited due to cumbersome and difficult approaches and
      many plant species with soft tissue are difficult to work with. Hence, developing
      simple and efficient methods for grafting and split root inoculation in these
      plants is of great importance. RESULTS: We report a split root inoculation system
      for the small legume M. truncatula as well as robust and reliable techniques of
      inverted-Y grafting and reciprocal grafting. Although the split root technique
      has been historically used for a variety of experimental purposes, we made it
      simple, efficient and reproducible for M. truncatula. Using our split root
      experiments, we showed the systemic long distance suppression of nodulation on a
      second wild type root inoculated after a delay, as well as the lack of this
      suppression in mutants defective in autoregulation. We demonstrated inverted-Y
      grafting as a method to generate plants having two different root genotypes. We
      confirmed that our grafting method does not affect the normal growth and
      development of the inserted root; the composite plants maintained normal root
      morphology and anatomy. Shoot-to-root reciprocal grafts were efficiently made
      with a modification of this technique and, like standard grafts, demonstrate that
      the regulatory signal defective in rdn1 mutants acts in the root. CONCLUSIONS:
      Our split root inoculation protocol shows marked improvement over existing
      methods in the number and quality of the roots produced. The dual functions of
      the inverted-Y grafting approach are demonstrated: it is a useful system to
      produce a plant having roots of two different genotypes and is also more
      efficient than published shoot-to-root reciprocal grafting techniques. Both
      techniques together allow dissection of long distance plant developmental
      regulation with very simple, efficient and reproducible approaches.

PMID- 22971439
TI  - Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory
      mechanism in the rat.
AB  - BACKGROUND: Kinins are mediators of pain and inflammation. Their role in
      thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was
      found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study
      was to investigate the mechanism by which peripheral B1R affects body core
      temperature in a rat model known to show up-regulated levels of B1R. METHODS:
      Male Sprague-Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p.) to enhance
      B1R expression. Control rats received the vehicle only. One week later, rectal
      temperature was measured in awake rats after i.p. injection of increasing doses
      (0.01 to 5 mg/kg) of des-Arg(9)-Bradykinin (BK) and Sar-[D-Phe(8)]des-Arg(9)-BK
      (B1R agonists) or BK (B2R agonist). The mechanism of B1R-induced hyperthermia was
      addressed using specific inhibitors and in rats subjected to subdiaphragmatic
      vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time
      polymerase chain reaction (qRT-PCR) and B1R was localized by confocal microscopy.
      RESULTS: B1R agonists (0.1 to 5 mg/kg) showed transient (5- to 30-minute) and
      dose-dependent increases of rectal temperature (+1.5 degrees C) in STZ-treated
      rats, but not in control rats. BK caused no effect in STZ and control rats. In
      STZ-treated rats, B1R agonist-induced hyperthermia was blocked by
      antagonists/inhibitors of B1R (SSR240612), cyclooxygenase-2 (COX-2) (niflumic
      acid) and nitric oxide synthase (NOS) (L-NAME), and after vagal nerve ligation.
      In contrast, COX-1 inhibition (indomethacin) had no effect on B1R agonist-induced
      hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the
      hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene
      related peptide in sensory C-fibers. CONCLUSION: B1R, which is induced in
      inflammatory diseases, could contribute to hyperthermia through a vagal sensory
      mechanism involving prostaglandins (via COX-2) and nitric oxide.

PMID- 22971440
TI  - Lipidomic profiling of model organisms and the world's major pathogens.
AB  - Lipidomics is a subspecialty of metabolomics that focuses on water insoluble
      metabolites that form membrane barriers. Most lipidomic databases catalog lipids
      from common model organisms, like humans or Escherichia coli. However, model
      organisms' lipid profiles show surprisingly little overlap with those of
      specialized pathogens, creating the need for organism-specific lipidomic
      databases. Here we review rapid progress in lipidomic platform development with
      regard to chromatography, detection and bioinformatics. We emphasize new methods
      of comparative lipidomics, which use aligned datasets to identify lipids changed
      after introducing a biological variable. These new methods provide an
      unprecedented ability to broadly and quantitatively describe lipidic change
      during biological processes and identify changed lipids with low error rates.

PMID- 22971441
TI  - Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in
      Iranian postmenopausal women.
AB  - The bone and fat interface is implicated in the pathogenesis of postmenopausal
      osteoporosis. The association between circulating omentin-1 levels and bone
      mineral density (BMD) in postmenopausal women has never been assessed. A total of
      382 healthy postmenopausal women were randomly selected. Omentin-1, visfatin,
      adiponectin, the receptor activator of nuclear factor-kappaB ligand (RANKL),
      osteoprotegerin, high sensitivity C-reactive protein, degradation products of C
      terminal telopeptides of type I collagen, and osteocalcin were measured by highly
      specific enzyme-linked immunosorbent assay methods. BMD was determined for the
      lumbar spine (L2-L4) and the proximal femur using dual-energy X-ray
      absorptiometry. In multivariable-adjusted linear regression, serum omentin-1
      levels were inversely correlated with BMD at the lumbar spine (beta=-0.11,
      p=0.020). In multiple regression analyses, serum visfatin and adiponectin levels
      were not significantly correlated with BMD at different skeletal sites after
      controlling for age, body mass index, and bone-related markers. However, the
      highest quartile of adiponectin compared to the lowest quartile, after adjusting
      for potential confounders, revealed an inverse association with BMD in the lumbar
      spine (beta=-0.19, p=0.010). In conclusion, circulating omentin-1 levels had an
      inverse correlation with BMD at the lumbar spine in Iranian postmenopausal women.
      To further understand the role of omentin-1 in bone and mineral metabolism, large
      scale longitudinal studies focusing on BMD and osteoporotic fractures are
      warranted.

PMID- 22971443
TI  - Kilts, governance, and information technology: change is coming to SOGC.

PMID- 22971442
TI  - Mento-anterior face presentation in a primigravida.

PMID- 22971444
TI  - Fundamental errors in the Canadian Institute for Health Information's "risk
      adjusted rate" for caesarean sections will yield misleading results.

PMID- 22971445
TI  - At the forefront of a new research culture for collaborative perinatal research.

PMID- 22971446
TI  - The Society of Obstetricians and Gynaecologists of Canada's position statement on
      federal budget cuts to the Interim Federal Health Program.

PMID- 22971447
TI  - The Society of Obstetricians and Gynaecologists of Canada's position statement on
      federal budget cuts to the Interim Federal Health Program.

PMID- 22971448
TI  - A contemporary approach to the obstetric management of women with heart disease.
AB  - OBJECTIVES: Recommendations for the peripartum obstetric management of women with
      heart disease have included early induction of labour, shortening the second
      stage of labour during vaginal delivery, and low threshold for elective Caesarean
      section, although such techniques may result in complications. The objective of
      this study was to determine whether a less aggressive approach without routine
      preterm induction, shortening of the second stage, or Caesarean section adversely
      affects the mother or neonate. METHODS: We examined peripartum obstetric
      management and its relationship with adverse maternal and neonatal outcomes in
      1677 pregnancies: 559 in women with heart disease and 1118 in women without heart
      disease (control subjects). Logistic regression with propensity matching was used
      to compare outcomes in women with and without heart disease. RESULTS: Women with
      heart disease were more likely than control subjects to undergo induction of
      labour (P < 0.001). Induction of labour tended to be at term and for logistical
      reasons, not for the indication of maternal heart disease. Assisted vaginal
      deliveries were more common in women with heart disease (29% vs. 11%, P < 0.001)
      than in those without, and the second stage of labour was also more prolonged in
      women with heart disease. Rates  of Caesarean section were similar in both groups
      (P = 0.66).  A significant proportion of women with heart disease had unassisted
      vaginal deliveries. Invasive cardiac monitoring was rarely used. Adverse maternal
      cardiac events at delivery were rare (2% of pregnancies) and were not associated
      with mode of delivery. In multivariate analysis, maternal heart disease was not
      predictive of adverse neonatal events or third- or fourth- degree lacerations.
      Maternal heart disease was associated with postpartum hemorrhage, but this was
      not related to assisted delivery or prolonged second stage of labour. CONCLUSION:
      This large study has shown that in women with heart disease, avoidance of early
      induction of labour, rare use of Caesarean section for cardiac indications, and
      selective use of invasive monitoring produces safe obstetric outcomes.

PMID- 22971449
TI  - Validation of a prediction model for predicting the probability of morbidity
      related to a trial of labour in Quebec.
AB  - BACKGROUND: Pregnant women with a history of previous Caesarean section face the
      decision either to undergo an elective repeat Caesarean section (ERCS) or to
      attempt a trial of labour with the goal of achieving a vaginal birth after
      Caesarean (VBAC). Both choices are associated with their own risks of maternal
      and neonatal morbidity. We aimed to determine the external validity of a
      prediction model for the success of trial of labour after Caesarean section
      (TOLAC) that could help these women in their decision-making. METHODS: We used a
      perinatal database including 185,437 deliveries from 32 obstetrical centres in
      Quebec between 2007 and 2011 and selected women with one previous Caesarean
      section who were eligible for a TOLAC. We compared the frequency of maternal and
      neonatal morbidity between women who underwent TOLAC and those who underwent an
      ERCS according to the probability of success of TOLAC calculated from a published
      model of prediction. RESULTS: Of 8508 eligible women, including 3113 who
      underwent TOLAC, both maternal and neonatal morbidities became less frequent as
      the predicted chance of VBAC increased (P < 0.05). Women undergoing a TOLAC were
      more likely to have maternal morbidity than those who underwent an ERCS when the
      predicted probability of VBAC was less than 60% (relative risk [RR] 2.3; 95% CI
      1.4 to 4.0); conversely, maternal morbidity was not different between the two
      groups when the predicted probability of VBAC was at least 60% (RR 0.8; 95% CI
      0.6 to 1.1). Neonatal morbidity was similar between groups when the probability
      of VBAC success was 70% or greater (RR 1.2; 95% CI 0.9 to 1.5). CONCLUSION: The
      use of a prediction model for TOLAC success could be useful in the prediction of
      TOLAC success and perinatal morbidity in a Canadian population. Neither maternal
      nor neonatal morbidity are increased with a TOLAC when the probability of VBAC
      success is at least 70%.

PMID- 22971450
TI  - Ethnicity-specific growth distributions for prediction of newborn morbidity.
AB  - OBJECTIVES: Birth weight distributions differ according to the ethnic origin of
      the mother. We aimed to determine whether using ethnicity-specific growth
      distributions would identify newborns at risk for adverse infant outcomes
      associated with small for gestational age (SGA) birth better than population
      based distributions. METHODS: We examined 2647 singletons born to healthy non
      smoking mothers at British Columbia Women's Hospital at 37 to 41 completed weeks'
      gestation. We compared the ability of ethnicity-specific growth distributions and
      population-based distributions to predict which infants were at increased risk of
      adverse outcomes associated with SGA, as well as extended length of stay in
      hospital, using crude and adjusted odds ratios. RESULTS: The ethnicity-specific
      growth distributions were associated with an increased risk of adverse infant
      outcomes while the population-based distributions were not (adjusted odds ratio
      [aOR] 1.49 [95% CI 0.82 to 2.70] vs. aOR 0.88 [95% CI 0.48 to 1.64]). While both
      distributions predicted extended length of stay in hospital, this likely reflects
      clinicians' use of the population-based distribution to identify SGA infants.
      CONCLUSIONS: The use of ethnicity-specific growth distributions  will likely
      improve our ability to differentiate between babies  who are pathologically small
      and those who are constitutionally small, and prevent misclassification of
      constitutionally small but healthy newborns born to mothers of Chinese or South
      Asian descent as SGA.

PMID- 22971451
TI  - Ten-year, thirty-year, and lifetime cardiovascular disease risk estimates
      following a pregnancy complicated by preeclampsia.
AB  - OBJECTIVE: To calculate the cardiovascular disease (CVD) risk estimates for women
      following a pregnancy with or without preeclampsia. METHODS: We calculated 10
      year, 30-year, and lifetime CVD risk estimates at one year postpartum for women
      recruited into the Pre-Eclampsia New Emerging Team's prospective cohort. RESULTS:
      Complete CVD risk screening data were obtained from 118 control women and 99
      preeclamptic women. A total of 18.2% of preeclamptic women and 1.7% of control
      women had a high 10-year risk (OR 13.08; 95% CI 3.38 to 85.5), 31.3% of
      preeclamptic women and 5.1% of control women had a high 30-year risk (OR 8.43;
      95% CI 3.48 to 23.23), and 41.4% of preeclamptic women and 17.8% of control women
      had a high lifetime risk for CVD (OR 3.25; 95% CI 1.76 to 6.11). CONCLUSIONS: The
      association of preeclampsia with the future development of CVD makes pregnancy an
      early window of opportunity for the preservation of health and prevention of CVD.

PMID- 22971452
TI  - Risk estimation of metabolic syndrome at one and three years after a pregnancy
      complicated by preeclampsia.
AB  - BACKGROUND: Our goal was to determine the prevalence of metabolic syndrome in
      women following a pregnancy complicated by preeclampsia and to determine whether
      this changes between one- and three-years postpartum. METHODS: We recruited women
      into a longitudinal prospective  cohort following a pregnancy with or without
      preeclampsia.  The prevalence of cardiometabolic factors were assessed at  one-
      and three-years postpartum. A total of 217 women completed a visit at one year
      postpartum (n = 99 preeclampsia, n = 118 control subjects) and 120 completed a
      visit at three-years  (n = 73 preeclampsia, n = 47 control subjects). RESULTS:
      The prevalence of metabolic syndrome at one- and three-years postpartum was
      significantly greater in women who had preeclampsia (18.18% at one year, 21.92%
      at three-years) than in control subjects (6.78%, 6.38%) (P < 0.05), but did not
      change over time. CONCLUSIONS: Given the difficulty in following women long-term,
      either clinically or as part of study, and because cardiometabolic factors do not
      change significantly between one- and three-years postpartum, strategies for
      health preservation and disease prevention should be adopted in the first-year
      postpartum.

PMID- 22971453
TI  - A population-based study of antenatal corticosteroid prophylaxis for preterm
      birth.
AB  - OBJECTIVE: National and international clinical practice guidelines, based on the
      meta-analysis of randomized trials, recommend antenatal corticosteroid (ACS)
      prophylaxis for threatened preterm delivery. We carried out a study to determine
      the extent to which current clinical practice in British Columbia adheres to
      these guidelines with a focus on preterm deliveries at 33 to 34 weeks of
      gestation. METHODS: Data were obtained from the British Columbia Perinatal
      Database Registry, a comprehensive provincial registry containing detailed
      information on all births in the province. All preterm live births between 2000
      and 2009 were included in the study. The rate of ACS administration was assessed
      in different gestational age groups. Determinants of ACS administration (such as
      maternal characteristics and obstetric factors) were also studied. The frequency
      of ACS prophylaxis was estimated using rates and exact 95% confidence intervals,
      and associations were assessed using odds ratios and 95% confidence intervals.
      RESULTS: Among 35 862 preterm births in British Columbia, the rate of ACS
      administration was 56.0% in the 26- to 32-week group (95% CI 54.7% to 57.4%) and
      19.4% in the 33- to 34-week group (95% CI 18.5% to 20.4%). Rates were reasonably
      consistent between 2000 and 2009 and by region of residence in British Columbia.
      Women with hypertension (OR 1.51; 95% CI 1.32 to 1.72), gestational diabetes (OR
      1.21; 95% CI 1.05 t01.40), and iatrogenic deliveries (OR 1.34; 95% CI 1.22 to
      1.47) were significantly more likely to receive ACS. CONCLUSION: Despite explicit
      clinical guidelines, ACS usage in preterm deliveries at 33 to 34 weeks of
      gestation appears to be suboptimal.

PMID- 22971454
TI  - A national study of the provision of oncofertility services to female patients in
      Canada.
AB  - OBJECTIVE: This study aimed to gain a better understanding of the fertility
      preservation services provided by Canadian fertility clinics to women with
      cancer. METHODS: We invited a total of 76 fertility clinics across Canada to
      complete a mailed questionnaire related to the availability, accessibility,
      affordability, and utilization of fertility preservation services for oncology
      patients. RESULTS: The total response rate was 59.2%: 72.4% for IVF clinics and
      51.1% for fertility centres without on-site IVF. Not all the responding IVF
      centres accepted oncology referrals for women. Six clinics without on-site IVF
      accepted cancer patients for consultation. The medical consultation fees are
      covered by public health insurance in all provinces. The majority of respondents
      expedited the referrals to schedule an initial medical appointment within three
      days. Despite that, the referral volume reported by respondents was markedly low
      for all except two facilities. With over 4000 young women of reproductive age
      given a diagnosis of cancer each year in Canada, the findings suggest that cancer
      patients are severely under-served by fertility clinics. CONCLUSION: There is a
      need to develop a stronger partnership between the fields of oncology and
      reproductive medicine to further improve access of patients with cancer to
      fertility preservation services. Development of evidence-based practice
      guidelines covering medical, clinical, psychosocial, ethical, and legal aspects
      geared to the Canadian health care system would help to avoid ambiguity relating
      to the roles and responsibilities in the provision of fertility preservation
      services. Such processes would ensure optimization of services so that all young
      cancer patients would receive the best care in protecting their fertility.

PMID- 22971455
TI  - The safety of testosterone therapy in women.
AB  - Hypoactive sexual desire disorder (HSDD), a subset of female sexual dysfunction,
      causes personal distress for surgically and naturally postmenopausal and
      premenopausal women. HSDD has a multi-factorial etiology, including psychosocial
      factors such as relationship issues and medical factors such as medications,
      chronic illnesses, and hormonal effects. Although no androgen therapies for
      female sexual dysfunction are currently approved for use in Canada, clinical
      trials support the efficacy and short-term safety of testosterone therapy for
      HSDD. We review the scientific evidence for the safety of testosterone therapy
      for HSDD.

PMID- 22971456
TI  - Serum albumin levels in women with ovarian hyperstimulation syndrome with or
      without polycystic ovaries.
AB  - OBJECTIVE: To evaluate serum albumin levels in women with and without polycystic
      ovaries (PCO) before and during the development of ovarian hyperstimulation
      syndrome (OHSS), and to compare them with control women who did not develop OHSS.
      METHODS: We conducted a case-control study in a teaching hospital in which 49
      women who developed OHSS after ovarian follicular stimulation for infertility
      were evaluated and compared with 91 control women who did not develop OHSS. The
      main outcome measures were levels of serum albumin, measured once in control
      subjects and before and after the development of OHSS in cases. RESULTS: Among
      women who developed OHSS, 30 had PCO and 19 others had no PCO. The mean baseline
      serum albumin level in women with PCO who subsequently had severe OHSS (38.8 +/-
      1.0 g/L) was lower than in those who developed moderate OHSS (41.8 +/- 0.8 g/L)
      (P < 0.05) and in the control group  (41.7 +/- 0.4 g/L) (P < 0.03). CONCLUSION:
      Baseline serum albumin levels in women with PCO who subsequently develop severe
      OHSS are lower than in those who develop moderate OHSS or do not develop OHSS.
      Confirmation of these findings with a large study is needed.

PMID- 22971457
TI  - Emergency contraception.
AB  - OBJECTIVE: To review current knowledge about emergency contraception (EC),
      including available options, their modes of action, efficacy, safety, and the
      effective provision of EC within a practice setting. OPTIONS: The combined
      estradiol-levonorgestrel (Yuzpe regimen) and the levonorgestrel-only regimen, as
      well as post-coital use of copper intrauterine devices, are reviewed. OUTCOMES:
      Efficacy in terms of reduction in risk of pregnancy, safety, and side effects of
      methods for EC and the effect of the means of access to EC on its appropriate use
      and the use of consistent contraception. EVIDENCE: Studies published in English
      between January 1998 and March 2010 were retrieved though searches of Medline and
      the Cochrane Database, using appropriate key words (emergency contraception, post
      coital contraception, emergency contraceptive pills, post-coital copper IUD).
      Clinical guidelines and position papers developed by health or family planning
      organizations were also reviewed. VALUES: The studies reviewed were classified
      according to criteria described by the Canadian Task Force on Preventive Health
      Care, and the recommendations for practice were ranked according to this
      classification (Table 1). BENEFITS, HARMS, AND COSTS: These guidelines are
      intended to help reduce unintended pregnancies by increasing awareness and
      appropriate use of EC. SPONSOR: The Society of Obstetricians and Gynaecologists
      of Canada. Summary Statements 1. Hormonal emergency contraception may be
      effective if used up to 5 days after unprotected intercourse. (II-2) 2. The
      earlier hormonal emergency contraception is used, the more effective it is. (II
      2) 3. A copper IUD can be effective emergency contraception if used within 7 days
      after intercourse. (II-2) 4. Levonorgestrel emergency contraception regimens are
      more effective and cause fewer side effects than the Yuzpe regimen. (I) 5.
      Levonorgestrel emergency contraception single dose (1.5 mg) and the 2-dose
      levonorgestrel regimen (0.75 mg 12 hours apart) have similar efficacy with no
      difference in side effects. (I) 6. Of the hormonal emergency contraception
      regimens available in Canada, levonorgestrel-only is the drug of choice. (I) 7. A
      pregnancy that results from failure of emergency contraception need not be
      terminated (I) Recommendations 1. Emergency contraception should be used as soon
      as possible after unprotected sexual intercourse. (II-2A) 2. Emergency
      contraception should be offered to women if unprotected intercourse has occurred
      within the time it is known to be effective (5 days for hormonal methods and up
      to 7 days for a copper IUD). (II-2B) 3. Women should be evaluated for pregnancy
      if menses have not begun within 21 days following emergency contraception
      treatment. (III-A) 4. During physician visits for periodic health examinations or
      reproductive health concerns, any woman in the reproductive age group who has not
      been sterilized may be counselled about emergency contraception in advance with
      detailed information about how and when to use it. (III-C).

PMID- 22971458
TI  - Implementation and impact of anti-smoking interventions in three prisons in the
      absence of appropriate legislation.
AB  - OBJECTIVE: To assess the acceptability and impact of anti-smoking policies in
      three prisons in Switzerland. METHODS: A before-after intervention study in A) an
      open prison for sentenced prisoners, B) a closed prison for sentenced prisoners,
      and C) a prison for pretrial detainees. Prisoners and staff were surveyed before
      (2009, n=417) and after (2010-2011, n=228) the interventions. Medical staff were
      trained to address tobacco dependence systematically in prisoners. In prison A, a
      partial smoking ban was extended. No additional protection against second-hand
      smoke was feasible in prisons B and C. RESULTS: In prison A, more prisoners
      reported receiving medical help to quit smoking in 2011 (20%) than in 2009 (4%,
      p=0.012). In prison A, prisoners and staff reported less exposure to second-hand
      smoke in 2011 than in 2009: 31% of prisoners were exposed to smoke at workplaces
      in 2009 vs 8% in 2011 (p=0.001); in common rooms: 43% vs 8%, (p<0.001). No
      changes were observed in prisons B and C. CONCLUSIONS: Reinforcement of non
      smoking rules was possible in only one of the three prisons but had an impact on
      exposure to tobacco smoke and medical help to quit. Implementing anti-smoking
      policies in prisons is difficult in the absence of appropriate legislation.

PMID- 22971460
TI  - The 12th edition of the European Symposium on Controlled Drug Delivery,
      (ESCDD2012) April 4-6, 2012, Egmond aan Zee, The Netherlands. Preface.

PMID- 22971459
TI  - Using population genetic methods to identify the origin of an invasive population
      and to diagnose cryptic subspecies of Telchin licus (Lepidoptera: Castniidae).
AB  - Telchin licus, the giant sugarcane borer, is an important pest species of
      sugarcane in northeast Brazil. Four subspecies of Telchin licus are recognized in
      Brazil based on their geographic distribution and subtle differences in wing
      colour pattern. Some taxa are morphologically indistinguishable, and their
      accurate identification is key to their efficient control. Mitochondrial genes
      sequences (cytochrome oxidase I and subunit 6 of the nicotinamide adenine
      dinucleotide dehydrogenase) were applied to delimit taxonomic entities of T.
      licus, and to infer the origin of a newly established population in the state of
      Sao Paulo. The molecular data indicated that specimens sampled at different
      regions in Brazil are morphologically cryptic but genetically isolated entities,
      and at least three subspecies were assigned to the sampled localities. These data
      also suggested that the population collected from the state of Sao Paulo must
      have a common origin with populations from northeast Brazil, which corroborate
      the hypothesis that ornamental plants infested with larvae of T. licus might have
      been transported from the northeast to the southeast regions.

PMID- 22971461
TI  - Scientific Meeting at the Dakar (Senegal) site of the French National Agency for
      AIDS Research (ANRS), 31 May 2012.

PMID- 22971462
TI  - In vitro cell subtype-specific transduction of adeno-associated virus in mouse
      and marmoset retinal explant culture.
AB  - Adeno-associated virus (AAV) is a non-pathogenic human parvovirus that can infect
      both non-proliferating and proliferating cells. Owing to its favorable safety
      profile, AAV is regarded as suitable for clinical purposes such as gene therapy.
      The target cell types of AAV depend largely on the serotype. In the retina, AAV
      has been used to introduce exogenous genes into photoreceptors, and photoreceptor
      specific enhancers/promoters are used in most cases. Therefore, serotype
      specificity of AAV in retinal subtypes is unclear, particularly in vitro. We
      compared its infection profile in mouse and monkey retinas using EGFP under the
      control of the CAG promoter, which expressed the gene ubiquitously and strongly
      regardless of cell type. AAV1, 8, and 9 infected the horizontal cells when an
      embryonic day-17 retina was used as a host. Amacrine cell was also a major target
      of AAVs, and a small number of rod photoreceptors were infected. When adult
      retinas were used as a host, the main target of AAV was Muller glia. A small
      number of rod photoreceptors were also infected. In the adult common marmoset
      retina, rod and cone photoreceptors were efficiently infected by AAV1, 8, and 9.
      A portion of the Muller glia and amacrine cells were also infected. In summary,
      the infection specificity of different AAV serotypes did not differ, but was
      dependent on the stage of the host retina. In addition, infection specificities
      differed between mature marmoset retinas and mature mouse retinas.

PMID- 22971463
TI  - Nationwide inventory of mosquito biodiversity (Diptera: Culicidae) in Belgium,
      Europe.
AB  - To advance our restricted knowledge on mosquito biodiversity and distribution in
      Belgium, a national inventory started in 2007 (MODIRISK) based on a random
      selection of 936 collection points in three main environmental types: urban,
      rural and natural areas. Additionally, 64 sites were selected because of the risk
      of importing a vector or pathogen in these sites. Each site was sampled once
      between May and October 2007 and once in 2008 using Mosquito Magnet Liberty Plus
      traps. Diversity in pre-defined habitat types was calculated using three indices.
      The association between species and environmental types was assessed using a
      correspondence analysis. Twenty-three mosquito species belonging to traditionally
      recognized genera were found, including 21 indigenous and two exotic species.
      Highest species diversity (Simpson 0.765) and species richness (20 species) was
      observed in natural areas, although urban sites scored also well (Simpson 0.476,
      16 species). Four clusters could be distinguished based on the correspondence
      analysis. The first one is related to human modified landscapes (such as urban,
      rural and industrial sites). A second is composed of species not associated with
      a specific habitat type, including the now widely distributed Anopheles plumbeus.
      A third group includes species commonly found in restored natural or bird
      migration areas, and a fourth cluster is composed of forest species. Outcomes of
      this study demonstrate the effectiveness of the designed sampling scheme and
      support the choice of the trap type. Obtained results of this first country-wide
      inventory of the Culicidae in Belgium may serve as a basis for risk assessment of
      emerging mosquito-borne diseases.

PMID- 22971464
TI  - Vascular pathology of multiple sclerosis.

PMID- 22971465
TI  - Arterial, venous and other vascular risk factors in multiple sclerosis.
AB  - PURPOSE OF REVIEW: This article reviews vascular risk factors with specific
      emphasis on lipid abnormalities reported to be associated with multiple sclerosis
      (MS). RECENT FINDINGS: The current paradigm of MS, supported only partially by MS
      lesion histopathology and its animal model (experimental allergic
      encephalomyelitis) considers MS to be a predominantly autoimmune disease. Until
      recently, most of the known risk factors for MS were interpreted in the context
      of the autoimmune theory, which still fails to explain why genetically close
      populations exposed to similar pathogens and/or environmental risk factors have
      different incidences of MS. Therapies which partially modulate the inflammatory
      arm of MS pathogenesis, fail to achieve similar benefits in later disease stages,
      when less inflammatory lesions and more neurodegeneration are present. Several
      studies have reported an increased cardiovascular morbidity in MS patients and
      that vascular comorbidity at any time during the disease course also increased
      the risk of progressive disability. A condition named chronic cerebrospinal
      venous insufficiency provided a different perspective, on the possible
      association of MS with the abnormalities of the venous system. Our recent
      findings revealed increased prevalence of chronic cerebrospinal venous
      insufficiency associated with MS disease progression as well as with other
      neurologic disorders. On the other hand, recently emerging evidence indicates
      that there is an association between lipoproteins and cholesterol metabolism and
      MS disease progression. Expanded disability status scale worsening was associated
      with higher baseline low-density lipoprotein and total cholesterol, and higher
      serum high-density lipoprotein levels were associated with lower contrast
      enhancing T1-weigthed lesion volume. It is thought that apolipoprotein A-1 and
      paraoxonase anti-oxidant enzyme are associated with high-density lipoprotein and
      contribute to its anti-oxidant and anti-inflammatory properties. A significant
      inter-dependence was also recently demonstrated between vitamin D, one of the
      best known environmental risk factors for MS and MS disease progression and the
      serum lipid profile. Future work in this direction is required in order to better
      elucidate the role of lipid metabolism and vascular pathology in pathogenesis of
      MS.

PMID- 22971466
TI  - Anti-phospholipid antibodies are associated with response to interferon-beta1a
      treatment in MS: results from a 3-year longitudinal study.
AB  - OBJECTIVES: To prospectively investigate the associations of baseline serum anti
      phospholipid antibody (APLA) status on evolution of clinical and MRI measures in
      a multiple sclerosis (MS) patient cohort treated with interferon-beta (IFN-beta).
      METHODS: Forty-seven relapsing-remitting (RR) MS patients, [26 APLA-positive
      (APLA(+)) and 21 APLA-negative (APLA(-))] matched for age, sex, disease duration,
      MRI characteristics, disability, and time on IFN-beta treatment, were enrolled.
      All patients were on intramuscular (IM) IFN-beta1a for at least 3 years and
      remained on the same treatment over the 3-year duration of the study. RESULTS:
      The APLA(+) group accumulated significantly higher T2-LV over the 3-year follow
      up than the APLA(-) group (+31% versus -1.1%, P = 0.043). The MTR of T1-LV (-3.3%
      versus +4.7%, P = 0.04) in the APLA(+) group was lower compared to the APLA(-)
      group. At 3-year follow-up, the APLA(+) group had increased tissue damage as
      measured by diffusion entropy (+4% versus -2.5%, P = 0.019) and whole brain
      volume loss (-0.69% versus -0.37%, P = 0.041), compared to the APLA(-) group.
      There were more clinical relapses in the MS APLA(+) group compared to APLA(-)
      patients (18 versus 10) and a higher frequency of sustained disability
      progression (7/26 or 27% versus 2/21 or 9.5%). CONCLUSIONS: This study suggests
      that APLA(+) RRMS patients treated with IFN-beta1a develop more severe MRI and
      clinical deterioration. Future studies are required to evaluate the role of APLA
      as potential biomarkers for disease prognosis versus predictors for therapeutic
      response to IFN-beta therapy.

PMID- 22971467
TI  - CCSVI is associated with multiple sclerosis.
AB  - OBJECTIVES: To analyze all the arguments against chronic cerebrospinal venous
      insufficiency (CCSVI) as a medical entity, and its association with multiple
      sclerosis (MS) and to revise all the findings suggesting a possible connection
      between these two entities. METHODS: We revised the methodology and results of
      all fourteen published studies on prevalence of CCSVI in MS patients.
      Furthermore, we take into consideration other work dealing with possible causes
      and explanations of venous, as well as vascular dysfunctions linked with MS.
      RESULTS: Studies  of prevalence show a great variability in prevalence of CCSVI
      in MS patients. However, a recent meta-analysis assessed an over 13 times
      increased prevalence in MS. Global hypoperfusion of the brain, and reduced
      cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Post
      mortem  studies show a higher prevalence of intraluminal defects in the main
      extracranial vein in MS patients in respect to controls. DISCUSSION: Taking into
      account the current epidemiological data, the autoptic findings, and the
      relationship between CCSVI and both hypoperfusion and cerebrospinal  fluid flow,
      CCSVI can be inserted in the list of multiple factors involved in MS
      pathogenesis. Our careful data analysis may conclude that great variability in
      prevalence of CCSVI in MS patients can be a result of different methodologies
      used in venous ultrasound assessment. Finally, it has  been proven that CCSVI
      share the three main risk factors with MS. On the other hand, smoking is the most
      important risk factor for endothelial cell damage, vitamin D has a protective
      role and Epstein-Barr virus passes the blood-brain barrier by invading the
      endothelial cells,  therefore, epidemiologically, linking the imbalance of these
      three factors to MS through autoimmunity.

PMID- 22971468
TI  - Magnetic resonance imaging signatures of vascular pathology in multiple
      sclerosis.
AB  - Venous vascular contributing factors to multiple sclerosis (MS) have been known
      for some time. Only recently has the scope of their potential role become more
      apparent with the theory of chronic cerebrospinal venous insufficiency (CCSVI).
      As research expands to further explore the role  of vascular pathology in the MS
      population, it is expedient to review the evidence from an imaging perspective.
      In this paper, we review the current state-of-the-art methods using magnetic
      resonance imaging (MRI) as applied to imaging MS patients and CCSVI. This
      includes evaluating imaging  signatures of vascular structure and flow as well as
      brain iron content. Upon review of the literature, we find that extracranial
      venous anomalies including stenosis, venous malformations, and collateralization
      of flow in the major veins of the neck have been observed to be prevalent in the 
      MS population. Abnormal flow has been reported in MS patients both in major
      vessels using phase-contrast flow quantification and in the brain using perfusion
      weighted imaging. We discuss the role of quantitative flow imaging and its
      potential in assessing possible biomarkers for abnormal flow.  Finally, it has
      been suggested that the presence of high iron content may indirectly indicate
      progression of existing vascular pathology. To that end, we review the use of
      susceptibility-weighted imaging in monitoring iron in the thalamus, basal
      ganglia, and MS lesions.

PMID- 22971469
TI  - Characteristics of flow through the internal jugular veins at cervical C2/C3 and
      C5/C6 levels for multiple sclerosis patients using MR phase contrast imaging.
AB  - OBJECTIVES: To study blood flow characteristics through the internal jugular
      veins (IJVs) at the cervical levels C2/C3 and C5/C6 in the neck of multiple
      sclerosis (MS) patients. METHODS: Magnetic resonance imaging at 3T was performed
      on 323 MS patients. Phase contrast  imaging was used to quantify blood flow at
      both the C2/C3 and C5/C6 levels. Total IJV flow (tIJF) was normalized by total
      arterial flow (tAF). Contrast-enhanced time-resolved 3D MR arteriovenography and
      2D time-of-flight MR venography were performed to assess IJV anatomy. Based on
      this assessment,  the MS population was divided into non-stenotic (NST) and
      stenotic (ST) subjects. RESULTS: Of all the patients, 100 (31%) belonged to the
      NST group and 223 (69%) belonged to the ST group. At the C2/C3 and C5/C6 levels,
      the normalized tIJF of the ST group was 56+/-26% and 51+/-23%,  respectively.
      This was significantly lower than that of the NST group, 85+/-13% and 73+/-12%
      (P<0.001). Zero percent and 5% of the NST group had a normalized tIJF of less
      than 50% at the C2/C3 and C5/C6 levels, compared to 37% and 47% for the ST group.
      The tAF was  smaller for the secondary and primary progressive MS patients than
      the relapsing remitting MS patients (P = 0.02 and 0.01, respectively), while the
      tIJF was similar among all MS types. CONCLUSION: Total blood flow through the
      IJVs at both the C2/C3  and C5/C6 levels was reduced in the ST group compared to
      the NST group.

PMID- 22971470
TI  - A technical approach to dissecting and assessing cadaveric veins pertinent to
      chronic cerebrospinal venous insufficiency in multiple sclerosis.
AB  - OBJECTIVE: To establish a detailed technical procedure for studying the
      anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers
      of multiple sclerosis and control subjects, and to present our findings of the
      normal anatomic venous structures, with reference  to previous descriptions from
      the literature. METHODS: This study examined the internal jugular veins (IJVs),
      the brachiocephalic veins, and the azygos vein from 20 cadavers (10 control and
      10 multiple sclerosis). These veins were exposed, isolated by clamps from the
      rest of the  venous system, flushed with water, and then injected with fluid
      silicone from the superior ends of both IJVs. After the silicone cured to its
      solid state, the venous tree was removed en bloc and dissected longitudinally to
      expose the luminal surface. All vein segments were analyzed  for anatomic
      variation. Anatomical analysis for this manuscript focused on normal vein
      architecture and its variants. RESULTS: Thirty-seven of 40 IJVs contained valves:
      29 bicuspid, 6 tricuspid, and 2 unicuspid. The average circumferences of the
      right and left IJVs were 2.2  and 1.8 cm, respectively. Thirteen of 20 azygos
      veins contained a valve, located on average 3.6 cm away from the superior vena
      cava junction. Nine of the 13 azygos valves were bicuspid; four were tricuspid.
      Only one of the 40 brachiocephalic veins contained a valve. DISCUSSION: We
      detailed a technical approach for harvesting cadaveric neck and thoracic veins
      with relevance to chronic cerebrospinal venous insufficiency. The anatomy of the
      venous system has significant variability, including differing number of valves
      in different regions and variable characteristics  of the valves. Average vein
      circumference was less than that typically reported in imaging studies of live
      patients.

PMID- 22971471
TI  - Heart disease, overweight, and cigarette smoking are associated with increased
      prevalence of extra-cranial venous abnormalities.
AB  - OBJECTIVES: Most of the extra-cranial venous abnormalities have been previously
      described as truncular venous malformations. In this hypothesis-driven study, we
      evaluated possible association of risk/protective factors with the presence of
      truncular and functional venous abnormalities in internal jugular veins (IJVs) in
      a large cohort of volunteers without known central nervous system (CNS)
      pathology. METHODS: The study included 240 controls who underwent physical and
      Doppler sonography (DS) examinations for the presence of intra- and extra-luminal
      structural and functional abnormalities of the IJVs, and were assessed with a
      physical examination and structured environmental questionnaire for demographic
      characteristics, presence of autoimmune and other concomitant diseases, vascular
      risk factors, environmental factors, and habits. Logistic regression analysis was
      used to test which risk/protective factors were associated with the presence and
      number of extra-cranial venous abnormalities. RESULTS: Subjects with heart
      disease (P<0.001), overweight (P = 0.005), and smoking (P = 0.016) had a
      significantly increased number of intra-luminal structural venous abnormalities.
      Presence of heart disease increased the risk of a malformed valve 12.9 times (95%
      CI: 5.4-31.3, P<0.001), while smoking increased it 2.21 times (95% CI: 1-4.9, P =
      0.033). Being overweight (P = 0.003), a history of mononucleosis (P = 0.012) and
      smoking (P = 0.042) increased risk for presence of a flap. No association was
      found between the investigated risk factors and extra-luminal or functional
      venous abnormalities. However, use of dietary and herbal supplements had a
      protective role for the presence of functional venous abnormalities. CONCLUSIONS:
      There is a close association between intra-luminal, structural, extra-cranial,
      venous system pathology and the presence of heart disease, overweight, and
      smoking.

PMID- 22971472
TI  - A randomized, prospective pilot study of patient expectancy and antidepressant
      outcome.
AB  - BACKGROUND: This study is a randomized, prospective, investigation of the
      relationships between clinical trial design, patient expectancy and the outcome
      of treatment with antidepressant medication. Method Adult out-patients with major
      depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50%
      probability of receiving active medication) or comparator (COMP, 100% probability
      of receiving active medication) administration of antidepressant medication.
      Independent-samples t tests and analysis of covariance (ANCOVA) were used to
      determine whether the probability of receiving active medication influenced
      patient expectancy and to compare medication response in the PC v. COMP
      conditions. We also tested the correlations between baseline expectancy score and
      final improvement in depressive symptoms across study groups. RESULTS: Subjects
      randomized to the COMP condition reported greater expectancy of improvement
      compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There
      were no statistically significant differences in the analyses comparing
      antidepressant outcomes between subjects receiving medication in the COMP
      condition and those receiving medication in the PC condition. Higher baseline
      expectancy of improvement was correlated with lower final depression severity
      scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over
      the course of the study (r = 0.44, p = 0.058). CONCLUSIONS: The methods described
      represent a promising way of subjecting patient expectancy to scientific study.
      Expectancy of improvement is affected by the probability of receiving active
      antidepressant medication and seems to influence antidepressant response.

PMID- 22971473
TI  - Fatty acid compositions of Taenia solium metacestode and its surrounding tissues.
AB  - Fatty acids (FAs) are the main energy sources of living organisms and are the
      major components of cellular and organelle membranes. Their compositions also
      affect the flexibility/rigidity of cells and cell vitality. The Taenia solium
      metacestode (TsM) causes neurocysticercosis (NC), which is one of the most common
      helminthic infections of the central nerve system. We investigated the FA
      composition of the cyst fluid (CF) and parenchyma of the TsM, together with those
      of the granuloma and swine tissue surrounding the granuloma. The FA fractions of
      the TsM CF and swine tissue showed a composition and proportional contents
      comparable to each other, in which C18:0 (stearic acid), C18:1n9c (oleic acid),
      C20:4 (arachidonic acid) and C16:0 (palmitic acid) constituted the major
      fractions. However, the relative amount of individual FAs of the TsM parenchyma
      and granuloma differed from those of TsM CF and swine tissue, which contained
      enriched C16:0 and a lower amount of C20:4. Saturated FAs were the major
      constituents in parenchyma and granuloma, 50.4% and 46.1%, respectively.
      Conversely, monounsaturated FAs were the major constituents of CF and swine
      tissue, 38.7% and 40.3%, respectively. Our results strongly suggest that host
      derived FAs might translocate across the parasite syncytial membrane and be
      stored in the CF.

PMID- 22971474
TI  - New agonist- and antagonist-based treatment approaches for advanced prostate
      cancer.
AB  - Increased understanding of prostate cancer biology has led to new treatment
      strategies and promising new agents for treating prostate cancer, in particular
      peptide-based agonists and antagonists. In this review article, new therapy
      modalities and potential approaches for the treatment  of advanced prostate
      cancer are discussed, including agonists and antagonists of luteinizing hormone
      releasing hormone, antagonists of bombesin/gastrin-releasing peptide, and growth
      hormone-releasing hormone and somatostatin analogues. Though the prognosis of
      patients with prostate cancer  is much improved by some of these treatment
      approaches, including combination treatment methods, extensive side-effects are
      still reported. These include sexual dysfunction, functional lesions of the liver
      and renal system, osteoporosis, anaemia and diarrhoea. Future studies should
      focus on  new treatment agents and treatment approaches that can eliminate side
      effects and improve quality of life in patients with prostate cancer on the basis
      of potent treatment efficacy.

PMID- 22971476
TI  - The role of telomeres in musculoskeletal diseases.
AB  - The telomeric region of repetitive DNA sequences at the end of chromosomes
      prevents end-to-end fusion of chromosome terminals and deterioration of the
      doublestrand free ends. Because of the 'end-replication problem', telomeres
      shorten with each round of cell division, resulting in cell  senescence. The
      enzyme telomerase compensates for telomere shortening by elongating telomeric
      sequences, thereby prolonging the lifespan of the cell. Studies of articular
      cartilage and bone tissues have indicated that telomere shortening limits normal
      cell function and proliferation, while  the telomere maintenance mechanisms of
      osteosarcoma cells facilitate escape from cell death and promote immortality.
      This article reviews the literature on this topic and provides an extensive
      discussion of the basic molecular biology and roles of telomeres and telomerase
      in musculoskeletal  diseases such as osteoarthritis, osteoporosis and
      osteosarcoma. Findings to date suggest that telomeres and telomerase may become
      novel therapeutic targets for the diagnosis, treatment and prevention of
      musculoskeletal disorders.

PMID- 22971475
TI  - Development and feasibility study of an algorithm for intraoperative goaldirected
      haemodynamic management in noncardiac surgery.
AB  - This study developed an evidence-based, goal-directed haemodynamic management
      algorithm to standardize intraoperative haemodynamic therapy. A systematic
      literature search identified three haemodynamic management goals: stroke volume
      optimization by fluid therapy; maintenance of a target mean arterial pressure by
      vasopressor therapy; maintenance of a target cardiac index>=2.5 l/min per m2 by
      inotropic therapy. The algorithm was adapted to international standards and
      consensus was reached through a modified Delphi method at international meetings.
      Implementation of the algorithm into routine intraoperative management in
      noncardiac surgery was shown to be feasible. Compared with conventional
      haemodynamic management, use of the algorithm significantly reduced length of
      hospital stay, requirement for ventilation and incidence of prolonged hospital
      stay, thereby resulting in reduced hospital costs.

PMID- 22971477
TI  - ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma
      cells in vitro and in vivo.
AB  - OBJECTIVE: This study investigated the potential synergistic effects of two
      inducers of apoptosis: the small molecule ABT-737 and arsenic trioxide (ATO).
      METHODS: Human gastric carcinoma cell lines SGC-7901 and MGC-803 were used to
      determine the effects of ABT-737 and ATO (alone or  in combination) on cell
      proliferation and apoptosis in vitro. In vivo effects of these drugs were
      investigated in SGC-7901 solid tumours, grown in immunodeficient mice. RESULTS:
      ABT-737 and ATO inhibited proliferation and induced apoptosis in SGC-7901 and MGC
      803 cells in concentration-  and time-dependent manners, and showed a synergistic
      effect. ABT-737 disturbed the binding of B cell lymphoma (Bcl)-2 homologous
      antagonist killer and Bcl-extra large; ATO downregulated myeloid cell leukaemia
      (Mcl)-1 protein and upregulated Mcl-1short, the short splicing variant. ABT-737
      and  ATO significantly suppressed SGC-7901 xenograft growth, synergistically
      inhibited tumour growth and induced apoptosis in vivo. CONCLUSIONS: This study
      provides preclinical evidence that ABT-737 and ATO synergize to induce apoptosis
      of gastric carcinoma cells, suggesting that further  investigation of these
      agents (as potential treatments for gastric cancer) is warranted.

PMID- 22971479
TI  - Elevated lysosome-associated protein transmembrane-4beta-35 is an independent
      prognostic marker in pancreatic carcinoma.
AB  - OBJECTIVES: To investigate the relationship between lysosome-associated protein
      transmembrane-4beta-35 (LAPTM4B-35) and the clinicopathological features and
      prognosis of pancreatic carcinoma. METHODS: The level of LAPTM4B-35 protein was
      determined by semi quantitative immunohistochemistry  in pancreatic carcinoma
      specimens. The relationship between LAPTM4B-35 level and prognosis was determined
      using univariate and multivariate analyses. RESULTS: A total of 98 patient
      samples were included. The presence of LAPTM4B-35 protein was confirmed in 77/98
      (78.6%) patients and was significantly  associated with tumour stage, degree of
      differentiation and pathological staging of pancreatic carcinoma after primary
      surgery. Patients with high LAPTM4B-35 levels had a poorer overall survival
      compared with patients with lower levels. Multivariate analysis showed that
      LAPTM4B-35 was an independent  prognostic factor for overall survival.
      CONCLUSIONS: LAPTM4B-35 was found to be present at high levels in a large
      proportion of patients with pancreatic carcinoma, and was closely related to
      disease progression and poor prognosis. LAPTM4B-35 may represent a new molecular
      target for the clinical  evaluation and treatment of pancreatic carcinoma.

PMID- 22971478
TI  - Autologous dendritic cells combined with cytokine-induced killer cells synergize
      low-dose chemotherapy in elderly patients with acute myeloid leukaemia.
AB  - OBJECTIVES: To investigate the possibility of culturing dendritic cells (DCs) and
      cytokine-induced killer (CIK) cells, obtained at initial diagnosis of AML in
      elderly patients, and to investigate the safety and efficacy of treatment with
      autologous DCs and CIK cells when administered  to these patients in combination
      with low-dose chemo therapy. METHODS: DCs and CIK cells obtained at initial
      diagnosis of AML in elderly patients were cultured and used in combination with
      low-dose chemo therapy to treat these patients (immunotherapy group). Elderly
      patients with AML treated  only with low-dose chemotherapy served as the control.
      Before treatment and on day 7 after treatment with autologous DCs and CIK cells,
      T cell subsets and cytokine levels were evaluated in the immunotherapy group.
      RESULTS: A total of 21 elderly patients with AML were included in the
      immunotherapy  group and 23 in the control group. The clinical efficacy in the
      immunotherapy group was greater than in the control group. The percentages of T
      cell subsets and cytokine levels after immunotherapy treatment were significantly
      higher than before the treatment. CONCLUSION: Immuno therapy with  autologous DCs
      and CIK cells was found to be a promising candidate for treatment of AML in
      elderly patients.

PMID- 22971480
TI  - Thrombospondin-1 and transforming growth factor-beta1 levels in prolactinoma and
      their clinical significance.
AB  - OBJECTIVE: To investigate the roles of angiogenesis, thrombospondin-1 (TSP-1) and
      transforming growth factor-beta1 (TGF-beta1) in invasive and noninvasive
      prolactinoma. METHODS: TSP-1 and TGF-beta1 protein were examined using
      immunohistochemistry and Western blotting in 81 prolactinomas. Angiogenesis was
      assessed by measuring microvessel density via CD34 immunostaining. RESULTS:
      Microvessel density was significantly higher in invasive prolactinomas than in
      noninvasive prolactinomas. Immunohistochemistry demonstrated that significantly
      fewer invasive prolactinomas were positive for TSP-1 compared with noninvasive
      prolactinomas (17.9% versus 50.0%, respectively), and significantly higher
      numbers of invasive prolactinomas were positive for TGF-beta1 compared with
      noninvasive prolactinomas (82.1% versus 42.9%, respectively). Microvessel density
      was significantly lower in TSP-1-positive prolactinomas than in TSP-1-negative
      prolactinomas, and significantly higher in TGF-beta1-positive prolactinomas than
      in TGF-beta1-negative prolactinomas. CONCLUSIONS: These results suggest a close
      relationship between angiogenesis and tumour invasiveness in prolactinoma. TSP-1
      and TGF-beta1 may play important roles in the progression of prolactinoma, by
      affecting angiogenesis.

PMID- 22971481
TI  - Relationship between fasting and 2-hour postprandial plasma glucose levels and
      vascular complications in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate the relationship between fasting and 2-h postprandial
      plasma glucose concentrations and vascular complications in type 2 diabetes.
      METHODS: Consecutive patients with type 2 diabetes admitted for blood glucose
      control were grouped according to their fasting and 2-h postprandial plasma
      glucose levels. Frequency and severity of diabetic retinopathy and nephropathy,
      number of carotid artery plaques, coefficient of variation of R-R intervals
      (CVRR), brachial-ankle pulse wave velocity (baPWV), intima-media thickness, brain
      natriuretic peptide level, ankle-brachial index, and high-sensitivity C-reactive
      protein levels were compared. RESULTS: In the 206 patients studied, mean+/-SD
      age, glycosylated haemoglobin and duration of diabetes were 63.4+/-13.7 years,
      9.8+/-1.8% and 13.4+/-8.9 years, respectively. Patients with high fasting plasma
      glucose levels had a higher frequency of proliferative retinopathy than those
      with low fasting levels. Patients with medium or high 2-h postprandial plasma
      glucose levels had higher baPWV and lower CVRR, respectively, than those with low
      2-h levels. There was an inverse correlation between baPWV and CVRR. CONCLUSION:
      Elevated fasting and postprandial plasma glucose levels are risk factors for
      vascular complications in type 2 diabetes mellitus.

PMID- 22971482
TI  - The adipose tissue endocrine mechanism of the prophylactic protective effect of
      pioglitazone in high-fat diet-induced insulin resistance.
AB  - OBJECTIVE: To explore the adipose tissue endocrine mechanism of pioglitazone and
      its possible prophylactic role in insulin resistance. METHODS: Male Wistar rats
      were randomized to receive a normal diet (N group), a high-fat insulin resistance
      inducing diet (IR group), or a high-fat diet plus treatment with pioglitazone (P
      group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11
      after starting the diet and, at week 12, adipose, liver and skeletal muscle
      tissue samples were taken. HepG2 cells were cultured with palmitic acid (PA),
      pioglitazone and PA plus pioglitazone, and RNA interference was used to
      downregulate adiponectin receptor (AdipoR) 2 in these cells. The mRNA and protein
      levels of adipokines (resistin and adiponectin), AdipoR1 and 2 and uptake of [3H]
      labelled glucose were measured in the HepG2 cells. RESULTS: Resistin and
      adiponectin in adipose tissue and AdipoR2 in liver tissue were significantly
      decreased in the IR group compared with the N group. Adiponectin and AdipoR2 were
      significantly increased and insulin resistance significantly decreased in the P
      group versus the IR group. In HepG2 cells, AdipoR2 levels and glucose uptake
      decreased significantly when PA was >=200 MUM, but were elevated by pioglitazone.
      Small interfering RNA-AdipoR2 confirmed glucose uptake in liver was regulated by
      AdipoR2. CONCLUSIONS: Pioglitazone prevented insulin resistance in rats fed a
      high-fat diet. Liver AdipoR2-mediated glucose uptake is important in the
      prophylactic effect of pioglitazone on insulin resistance.

PMID- 22971484
TI  - Altered aggrecan synthesis and collagen expression profiles in chondrocytes from
      patients with Kashin-Beck disease and osteoarthritis.
AB  - OBJECTIVES: To investigate cell morphology, aggrecan expression, and type I, II,
      III and X collagen expression in chondrocytes from adults with Kashin-Beck
      disease or osteoarthritis (OA). METHODS: Samples of knee articular cartilage were
      taken during surgery; cartilage samples  obtained from fresh cadavers without
      arthritic disease were used as controls. Samples were digested with collagenase;
      isolated chondrocytes were cultured in monolayers. Aggrecan was detected by
      toluidine blue staining; collagen and aggrecan protein levels were evaluated by
      immuno cytochemistry  and immuno fluorescence staining. RESULTS: Samples were
      obtained from six participants per group. Aggrecan and type II collagen levels in
      chondrocytes from patients were significantly lower than those from controls, but
      levels of type I, III and X collagen were enhanced in patients compared  with
      controls. Production of type III and X collagen was higher in chondrocytes from
      patients with Kashin-Beck disease than in those from OA patients. CONCLUSIONS:
      Biochemical and morphological mechanisms underlying Kashin-Beck disease and OA
      include enhanced dedifferentiation  and hypertrophy of chondrocytes, increased
      type I, III and X collagen levels, and suppressed type II collagen and aggrecan
      production compared with control samples.

PMID- 22971483
TI  - Higher serum retinol binding protein 4 may be a predictor of weak metabolic
      control in chinese patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate relationships between serum levels of retinol binding
      protein 4 (RBP4) and clinical and metabolic variables in Chinese patients with
      type 2 diabetes mellitus. METHODS: A total of 513 patients (286 males/227
      females) provided clinical and lifestyle data and blood and urine samples for
      analysis. Patients were stratified into four quartile groups according to serum
      RBP4 concentrations. RESULTS: RBP4 concentration was independently associated
      with gender, systolic blood pressure, serum triglyceride and creatinine levels,
      and estimated glomerular filtration rate (eGFR). Hypertension, dyslipidaemia,
      micro albuminuria and impaired eGFR (<60 ml/min per 1.73 m2) were significantly
      more prevalent in patients with the highest RBP4 levels than in those with the
      lowest levels. Increased serum RBP4 was associated with increased risk of
      hypertension, dyslipidaemia, micro albuminuria and impaired eGFR after adjusting
      for gender, age, body mass index and duration of diabetes. CONCLUSION: Serum RBP4
      may be a useful marker of overall metabolic control in Chinese patients with type
      2 diabetes mellitus.

PMID- 22971485
TI  - Intact versus fragmented 99mTc-monoclonal antibody imaging of infection in
      patients with septically loosened total knee arthroplasty.
AB  - OBJECTIVE: This prospective study compared the diagnostic accuracy of imaging
      using an intact murine antigranulocyte antibody 99mTc-besilesomab, and a murine
      antibody Fab fragment 99mTc-sulesomab, in patients with suspected septically
      loosened total knee arthroplasty. METHODS: Images from 20 patients who underwent
      threephase bone scintigraphy followed by imaging using 99mTc-besilesomab (n=10)
      or 99mTc-sulesomab (n=10) were evaluated and compared. Final diagnosis was
      determined by microbiological evaluation of aspirated synovial fluid,
      intraoperative samples through the clinical course, or by long-term follow-up.
      RESULTS: Prosthesis infection was shown in 18 patients. At 4 and 24 h after
      intravenous injection, absolute uptake of 99mTc-besilesomab was significantly
      higher than 99mTc-sulesomab in infected knee joints. Infected-to-healthy knee
      activity ratios were similar at 4 and 24 h for 99mTc-besilesomab and 99mTc
      sulesomab. CONCLUSIONS: Both 99mTc-besilesomab and 99mTc-sulesomab had similar
      diagnostic accuracy for the detection of septic arthroplasty. If repeated use of
      immunoscintigraphy is needed for follow-up, 99mTc-sulesomab should be preferred
      over 99mTc-besilesomab since it is known to be well tolerated and without side
      effects or incompatibility reactions.

PMID- 22971486
TI  - Comparison of a paraspinal approach with a percutaneous approach in the treatment
      of thoracolumbar burst fractures with posterior ligamentous complex injury: a
      prospective randomized controlled trial.
AB  - OBJECTIVE: This prospective randomized controlled study compared the efficacy and
      safety of two paraspinal muscle-sparing surgical approaches for the management of
      neurologically intact patients with thoracolumbar burst fractures and posterior
      ligamentous complex injuries. METHODS: Patients were randomized to undergo either
      percutaneous (n=31) or paraspinal (n=30) fluoroscopically-guided pedicle screw
      rod fixation, and were followed for >=3 years. Preoperative postural reduction
      was attempted in all patients. RESULTS: The percutaneous approach was associated
      with significantly less intraoperative blood loss and shorter duration of surgery
      and hospitalization, as well as less pain and better functional recovery at 3
      months after surgery compared with the paraspinal approach. Paraspinal surgery
      resulted in significantly better correction of kyphosis and restoration of
      vertebral height compared with percutaneous surgery. There were no differences in
      long-term clinical outcomes between the two groups. CONCLUSIONS: The minimally
      invasive percutaneous approach appears to be better in cases of successful
      postural reduction. The paraspinal approach results in better surgical correction
      and is, therefore, recommended for patients without successful postural
      reduction.

PMID- 22971487
TI  - Efficacy and tolerability of celecoxib versus naproxen in patients with
      osteoarthritis of the knee: a randomized, double-blind, double-dummy trial.
AB  - OBJECTIVE: To assess the efficacy and tolerability of celecoxib versus naproxen
      in patients with osteoarthritis (OA) of the knee. METHODS: This 6-month,
      randomized, double-blind, double-dummy trial was conducted at 47 centres in the
      USA. Patients with OA of the knee were randomized to receive 200 mg celecoxib
      orally once daily or 500 mg naproxen orally twice daily. The primary endpoint was
      defined as a 20% improvement from baseline to 6 months in Western Ontario and
      McMaster Universities (WOMAC) OA total score. RESULTS: A total of 586 out of 589
      randomized patients received at least one dose of celecoxib (n=294) or naproxen
      (n=292). The primary endpoint (6-month response rate) was achieved by 52.7% and
      49.7% of patients in the celecoxib and naproxen treatment groups, respectively.
      Significantly fewer discontinuations due to gastrointestinal adverse events
      occurred in patients receiving celecoxib than in those receiving naproxen (4.1%
      versus 15.1%, respectively). CONCLUSIONS: Over the 6month study period, celecoxib
      provided similar improvements in OA symptoms to naproxen. In addition, celecoxib
      provided better upper gastrointestinal tolerability than naproxen.

PMID- 22971488
TI  - Dexmedetomidine versus midazolam for conscious sedation in postoperative patients
      undergoing flexible bronchoscopy: a randomized study.
AB  - OBJECTIVE: This prospective randomized study evaluated the efficacy and patient
      tolerance of dexmedetomidine compared with midazolam for sedation in
      postoperative patients undergoing flexible bronchoscopy. METHODS: A total of 198
      postoperative patients were randomized to receive dexmedetomidine (n=99) or
      midazolam (n=99) to produce conscious sedation for bronchoscopy. Peripheral
      oxygen saturation, heart rate and systolic and diastolic arterial pressures were
      recorded before, during and after the procedure. Patient tolerance was recorded
      using various visual analogue scales. RESULTS: The mean lowest peripheral oxygen
      saturation was significantly lower in the midazolam group than in the
      dexmedetomidine group. Heart rate and systolic arterial pressure were both
      significantly higher during bronchoscopy in the midazolam group than in the
      dexmedetomidine group. Bronchoscopy was well tolerated in both groups; there was
      no between-group difference in patient discomfort scores or in the percentage of
      patients who would accept repeat bronchoscopy. CONCLUSIONS: Compared with
      midazolam, dexmedetomidine provided better oxygen saturation and was equally well
      tolerated for conscious sedation in postoperative patients undergoing
      bronchoscopy.

PMID- 22971489
TI  - High anxiety, young age and long waits increase the need for preoperative
      sedatives in children.
AB  - OBJECTIVE: This prospective, observational study aimed to identify children
      likely to require sedation preoperatively by measuring anxiety levels using the
      modified Yale Preoperative Anxiety Scale (mYPAS). Other possible predictive
      factors for preoperative sedation were also investigated. METHODS: A total of 455
      patients aged 2-12 years scheduled for surgery requiring general anaesthesia were
      enrolled in the study. Patients' anxiety levels were measured using the mYPAS in
      a preoperative holding area just before patients were separated from their
      parents or guardians and entered the operating theatre. Anaesthetists blindedto
      the mYPAS assessments judged whether the child could be separated and enter the
      operating theatre without a sedative. The ability of the mYPAS to predict the
      need for preoperative sedation was analysed by receiver operating characteristic
      (ROC) curve analysis. RESULTS: The optimum mYPAS cut-off for requiring sedatives
      was 41.7 according to ROC curve analysis. Multivariate logistic regression
      analysis showed that age, mYPAS>40 and waiting time were independent predictors
      of the requirement for sedative administration. CONCLUSIONS: High anxiety levels,
      young age and long waits contributed to the need for preoperative sedation in
      children.

PMID- 22971490
TI  - Bilateral superficial cervical plexus block reduces postoperative nausea and
      vomiting and early postoperative pain after thyroidectomy.
AB  - OBJECTIVE: To compare the incidence of postoperative nausea and vomiting (PONV)
      and postoperative pain in thyroidectomy patients undergoing general anaesthesia,
      with or without bilateral superficial cervical plexus block (BSCPB). METHODS: In
      this prospective, randomized, double-blind study, adult patients scheduled for
      thyroid surgery under general anaesthesia were randomized to receive BSCPB with
      20 ml 0.5% ropivacaine (ropivacaine group) or placebo (20 ml saline; saline
      group) before surgery. The incidence of PONV and postoperative pain, and the need
      for rescue antiemetics were assessed at 0-24 h postoperatively. RESULTS: Data
      from 135 patients were evaluated and the incidence of PONV, the need for rescue
      antiemetics and the number of patients needing additional perioperative pain
      relief in the postanaesthetic care unit were significantly lower in the
      ropivacaine group compared with the saline group. Early postoperative (0-8 h)
      visual analogue scale pain scores were significantly lower in the ropivacaine
      group compared with the saline group. CONCLUSIONS: BSCPB with 0.5% ropivacaine
      administered before surgery can significantly reduce the incidence of PONV and
      early postoperative pain and also reduce perioperative opioid requirements in
      thyroidectomy patients undergoing general anaesthesia.

PMID- 22971491
TI  - Autologous platelet-rich clot releasate stimulates proliferation and inhibits
      differentiation of adult rat tendon stem cells towards nontenocyte lineages.
AB  - OBJECTIVE: To explore the effects of autologous platelet-rich clot releasate
      (PRCR) on proliferation and differentiation of adult rat tendon stem cells (TSCs)
      in vitro, following intense mechanical stretching. METHODS: TSCs were subjected
      to 8% mechanical stretching and subsequently incubated in control medium or
      medium supplemented with 2% or 10% PRCR. Collagen types I and III, peroxisome
      proliferator-activated receptor-gamma (PPARgamma), sex determining region Y-box 9
      (SOX-9) and runt-related transcription factor 2 (RUNX2) concentrations were
      assessed via Western blotting and flow cytometry. Transforming growth factor
      (TGF)-beta1 and vascular endothelial growth factor concentrations were measured
      using enzyme-linked immunosorbent assay. Treated TSCs were also cultured in
      adipogenic, chondrogenic or osteogenic culture media. RESULTS: PRCR increased the
      number of TSCs, and the concentrations of collagen types I and III and TGF-beta1.
      In contrast, PRCR significantly reduced PPARgamma, SOX-9 and RUNX2-positive cell
      numbers, and significantly reduced the numbers of TSC-derived adipocytes,
      chondrocytes and osteocytes. CONCLUSION: PRCR induced tenocyte differentiation
      while suppressing the adipocyte, chondrocyte and osteocyte lineages believed to
      impede tendon healing.

PMID- 22971492
TI  - Clinical evaluation of extraperitoneal colostomy without damaging the muscle
      layer of the abdominal wall.
AB  - OBJECTIVE: This study investigated whether extraperitoneal colostomy without
      damaging the muscle layer of the abdominal wall is an improved surgical procedure
      compared with conventional sigmoid colostomy in patients undergoing
      abdominoperineal resection. METHODS: Patients with rectal  cancer undergoing
      abdominoperineal resection were selected and randomly divided into two groups:
      the study group received extraperitoneal colostomy without damaging the muscle
      layer of the abdominal wall and the control group received conventional
      colostomy. Clinical data from both groups  were analysed. RESULTS: A total of 128
      patients were included: 66 received extraperitoneal colostomy without damaging
      the muscle layer of the abdominal wall and 62 received conventional colostomy.
      Significant differences between the two groups were found in relation to
      colostomy operating  time, defaecation sensation, bowel control and overall stoma
      related complications. Duration of postoperative hospital stay was also
      significantly different between the study groups. CONCLUSIONS: Extraperitoneal
      colostomy without damaging the muscle layer of the abdominal wall was found to 
      be an improved procedure compared with conventional sigmoid colostomy in
      abdominoperineal resection, and may reduce colostomy-related complications,
      shorten operating time and postoperative hospital stay, and potentially improve
      patients' quality of life.

PMID- 22971493
TI  - Switching to an L/N-type calcium channel blocker shows renoprotective effects in
      patients with chronic kidney disease: the Kyoto Cilnidipine Study.
AB  - OBJECTIVE: This open-label, randomized controlled trial investigated the effects
      of cilnidipine, an L/N-type calcium channel blocker (CCB), in patients with
      chronic kidney disease (CKD). METHODS: Sixty patients with CKD and well
      controlled hypertension being treated with a renin-  angiotensin system (RAS)
      inhibitor and an L-type CCB (L-CCB) were randomly assigned either to switch from
      the L-CCB to cilnidipine after a 4-week observation period or to continue with L
      CCB treatment. Blood pressure, heart rate and renal function were monitored for
      12 months. Data were available  for analysis from 50 patients: 24 from the
      cilnidipine group and 26 from the L-CCB group. RESULTS: Blood pressure was well
      controlled in both groups. After 12 months, proteinuria and heart rate were
      significantly decreased in the cilnidipine group, but proteinuria increased and
      heart rate  remained unchanged in the L-CCB group. There was a significant
      positive correlation between the percentage changes in proteinuria and heart
      rate. CONCLUSIONS: Cilnidipine has antihypertensive effects equivalent to those
      of L-CCBs. In patients with CKD, proteinuria can be decreased by switching  from
      an L-CCB to cilnidipine, thereby improving renal function.

PMID- 22971494
TI  - Noninvasive evaluation of the chronic influence of local air velocity from an air
      conditioner using salivary cortisol and skin caspase-14 as biomarkers of
      psychosomatic and environmental stress.
AB  - OBJECTIVE: To demonstrate the possibility of evaluating the chronic influence of
      local air velocity from an air conditioner using noninvasive biomarkers. METHODS:
      Over a consecutive 5-day period, 16 healthy young male adults were exposed to air
      flow from a whole ceiling-type air conditioner (low local air velocity) and from
      a commercial concentrated exhaust air conditioner (high local air velocity).
      Salivary cortisol was used as an index of the psychological effects and caspase
      14, collected from the stratum corneum, was used as a marker of environmental
      stress on the skin. RESULTS: Local air velocity generated from the whole ceiling
      type air conditioner where the subject's head was positioned was one-seventh that
      of the exhaust air conditioner. After exposure to the exhaust air conditioner for
      5 days, salivary cortisol decreased significantly from morning to evening and
      skin caspase-14 gradually increased during the day. A significant increase in
      hydration index from the morning to the evening was found with the whole ceiling
      type air conditioner. CONCLUSION: The effects of chronic exposure to air movement
      generated by an air conditioner may be quantified by measurement of salivary
      cortisol and skin caspase-14.

PMID- 22971495
TI  - Naloxone inhibition of lipopolysaccharide-induced activation of retinal microglia
      is partly mediated via the p38 mitogen activated protein kinase signalling
      pathway.
AB  - OBJECTIVES: To investigate the effects and underlying mechanism of action of
      naloxone on lipopolysaccharide (LPS)-induced activation of retinal microglia in
      vitro. METHODS: Rat retinal microglia primary cultures were divided into four
      treatment groups: untreated; 1 MUg/ml LPS  for 12 h; 0.5, 1.0 or 2.0 MUM naloxone
      for 30 min before LPS; 2.5 or 5.0 MUM SB203580 for 12 h before LPS and naloxone.
      Levels of tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta were
      determined by enzyme-linked immuno sorbent assay. Western blot analysis and
      double immunofluorescence  were used to examine activation of the mitogen
      activated protein kinase (MAPK) signalling pathway. RESULTS: LPS induced an
      increase in TNF-alpha and IL-1beta in culture supernatants, which was dose
      dependently inhibited by naloxone. Naloxone also dose-dependently inhibited LPS
      induced  increases in phosphorylated p38 MAPK. Pretreatment of cells with
      SB203580 attenuated the inhibitory effect of naloxone on TNF-alpha and IL-1beta
      production. CONCLUSIONS: Naloxone suppressed LPS-induced activation of cultured
      retinal microglia and this suppression appeared to occur partly  through the p38
      MAPK signalling pathway. Naloxone may have therapeutic potential in neuro
      degenerative diseases characterized by the activation of microglia.

PMID- 22971496
TI  - Modification of the neurotrophin-3 gene promotes cholinergic neuronal
      differentiation and survival of neural stem cells derived from rat embryonic
      spinal cord in vitro and in vivo.
AB  - OBJECTIVE: To investigate the effects of the neurotrophin-3 (NTF3) gene on the
      survival and differentiation of neural stem cells (NSCs) in vitro and in vivo.
      METHODS: The NTF3 gene was isolated from rats, amplified by polymerase chain
      reaction (PCR) and subcloned into the lentiviral vector pWPXL-MOD to construct a
      lentiviral expression vector pWPXL-MOD-NTF3. Reverse transcription-PCR and
      Western blotting were used to analyse NTF3 mRNA and protein levels, respectively.
      Adult rats with sectioned tibial nerves received implants of NSCs transfected
      with either pWPXL-MOD-NTF3 (n=30) or an empty expression vector (n=30). In vitro
      and in vivo cell differentiation and survival were determined by fluorescence
      immunohistochemistry. RESULTS: Expression of NTF3 significantly increased the
      differentiation of NSCs into cholinergic neurons both in vitro and in vivo. NTF3
      expressing NSCs implanted into the tibial nerve also survived longer than cells
      without NTF3 gene modification. CONCLUSIONS: The NTF3 gene promoted
      differentiation of NSCs into cholinergic neurons and enhanced neuronal cell
      survival. These findings may have clinical implications for cell transplantation
      therapy in patients with nerve injury.

PMID- 22971497
TI  - A mathematical model for predicting outcome in preterm labour.
AB  - OBJECTIVE: This study aimed to develop a model for predicting the outcome and
      evaluating the treatment of patients with threatened of preterm labour. METHODS:
      Clinical data from 236 patients at <32 weeks gestation who were in preterm labour
      were analysed to develop a discriminant function using multiple logistic
      regression to identify significant risk factors. The function was validated
      retrospectively in a further 501 patients and prospectively in 63 patients with
      premature labour. RESULTS: Factors that increased the risk of preterm birth were
      premature rupture of the membranes, intrauterine infection, dilatation of the
      cervix and uterine bleeding. Factors that decreased the risk of preterm birth
      were hospital admission after 28 weeks of gestation and intravenous
      administration of ritodrine. The predictive accuracy of the function was 75.4% in
      the 236 patients analysed, 84.8% in the further 501 retrospectively studied
      patients and 85.7% in the prospective group. CONCLUSIONS: The discriminant
      function described was clinically useful for predicting the outcome of threatened
      preterm labour before initiating treatment and for determining the medical care
      of patients, including maternal transfer to a high-level perinatal care centre.

PMID- 22971498
TI  - Atypical antipsychotics do not reverse prepulse inhibition deficits in acutely
      psychotic schizophrenia.
AB  - OBJECTIVES: To investigate the effects of atypical antipsychotics on prepulse
      inhibition, startle response and habituation in acutely psychotic patients with
      schizophrenia, and investigate whether prepulse inhibition deficit improvements
      are a result of the direct impact of atypical  antipsychotics or improvements in
      antipsychotic-related symptoms. METHODS: Prepulse inhibition, habituation and
      acoustic startle response were evaluated in healthy control subjects and patients
      with schizophrenia (either unmedicated with antipsychotics at the time of
      hospitalization or medicated  with atypical antipsychotics for >=1 month before
      hospitalization). RESULTS: Data were analysed for 26 patients in the unmedicated
      group, 20 patients in the medicated group and 31 control subjects. Compared with
      controls, both medicated and unmedicated patients showed prepulse inhibition 
      deficits; however, there were no significant differences between the two patient
      groups. Lower prepulse inhibition levels were correlated with higher levels of
      positive, negative, general and total scores on the Positive and Negative
      Syndrome Scale. CONCLUSIONS: These results suggest that  effects of atypical
      antipsychotics on prepulse inhibition may not be evident when patients with
      schizophrenia are acutely symptomatic, and do not directly influence prepulse
      inhibition.

PMID- 22971499
TI  - Target-controlled infusion of remifentanil for laryngeal mask airway insertion
      during sevoflurane induction in adults.
AB  - OBJECTIVE: This randomized, double-blind study investigated the suitable target
      effect-site concentration of remifentanil for laryngeal mask airway (LMA)
      insertion during inhalation induction with sevoflurane. METHODS: Patients aged 18
      - 60 years were randomly assigned to one of three groups receiving infusions of
      normal saline (control group), or infusions with target effect-site remifentanil
      concentrations of either 1 ng/ml (R1 group) or 2 ng/ml (R2 group), 1 min after
      the induction of anaesthesia with sevoflurane. LMA insertion was attempted 2 min
      after induction. Insertion conditions were graded using a six-variable, three
      point scale (excellent, intermediate or poor). RESULTS: A total of 102 patients
      were included. The proportion of patients ranked as excellent for the LMA
      insertion was significantly higher in groups R1 and R2 compared with the control
      group. The incidence of apnoea was significantly more frequent in the R2 group
      than in the control or R1 groups. CONCLUSIONS: Compared with 1 ng/ml remifentanil
      or normal saline, target-controlled infusion of 2 ng/ml remifentanil
      significantly improved the LMA insertion conditions during sevoflurane
      inhalational induction, although apnoeic episodes were more frequently observed.

PMID- 22971500
TI  - Blood-brain barrier disruption is more severe in neuromyelitis optica than in
      multiple sclerosis and correlates with clinical disability.
AB  - OBJECTIVES: This study evaluated blood-brain barrier (BBB) integrity, using blood
      and cerebrospinal fluid (CSF) markers, and assessed the practicality of these
      markers in the differential diagnosis of neuromyelitis optica (NMO) and multiple
      sclerosis (MS). METHODS: This was a retrospective observational study of
      consecutive patients presenting with acute phase NMO or MS (first attack or
      relapse). Haematological tests (including antiaquaporin-4 antibody levels) and
      CSF parameters (using primary component analyses) were undertaken; the
      correlation between BBB permeability and disease severity (by Expanded Disability
      Status Scale [EDSS] score) was examined. RESULTS: Levels of several markers of
      BBB permeability were higher in patients with NMO (n=21) than in those with MS
      (n=52). The CSF:serum albumin ratio (AR) was the one of the main differentiators
      of NMO and MS. Additionally, there was a significant correlation between AR and
      clinical severity for NMO but not for MS. CONCLUSIONS: Markers of BBB
      permeability were significantly higher in NMO patients than in MS patients. AR
      was the best marker for differentiating NMO and MS. Thus, measurement of BBB
      disruption markers (such as AR) might help to differentiate the diagnosis of NMO
      and MS in acute clinical settings.

PMID- 22971501
TI  - Comparison of desflurane and sevoflurane anaesthesia in relation to the risk of
      vagally mediated reflex bradycardia during gastrectomy.
AB  - OBJECTIVE: This study compared the risk of clinically significant reflex
      bradycardia during anaesthesia with sevoflurane or desflurane in patients
      undergoing gastrectomy. METHODS: In this randomized prospective study, 100
      patients undergoing gastrectomy were assigned to receive sevoflurane (n=50) or
      desflurane (n=50) anaesthesia. No anticholinergic prophylaxis was administered.
      Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to
      <50 beats/min, or a decrease to 50-59 beats/min if associated with a systolic
      arterial pressure of 70 mmHg in response to surgical manoeuvres. If reflex
      bradycardia developed, atropine or ephedrine were administered according to a
      predefined treatment protocol. RESULTS: Data from 85 patients were available for
      analysis. The proportion of patients with symptomatic reflex bradycardia in the
      sevoflurane and desflurane groups was similar (69.0% versus 55.8%, respectively)
      and both groups required a similar amount of atropine and/or ephedrine.
      CONCLUSIONS: Clinically significant reflex bradycardia occurred with a relatively
      high frequency during gastrectomy. Although desflurane is associated with
      sympathetic activation, it did not provide a protective effect against vagally
      mediated reflex bradycardia during gastrectomy compared with sevoflurane.

PMID- 22971502
TI  - Changes in spontaneous dorsal horn potentials after dorsal root entry zone
      lesioning in patients with pain after brachial plexus avulsion.
AB  - OBJECTIVES: This study investigated spontaneous dorsal horn potentials in
      patients with pain after brachial plexus avulsion and determined the effect of
      dorsal root entry zone (DREZ) lesioning on these potentials and on pain levels.
      METHODS: Electrospinography (ESG) recordings were  undertaken in seven patients
      using a noninvasive electrocorticography strip electrode. Measurements were taken
      from the DREZ on the intact side of the spinal cord before lesioning of the
      injured DREZ and from the injured DREZ before and after lesioning. RESULTS: DREZ
      lesioning had a significant  positive effect on pain at 12 months
      postoperatively. At 15.0 Hz, the mean ESG power from the injured DREZ before
      lesioning was significantly higher than that from the intact DREZ. In addition,
      the mean ESG power from the injured DREZ after successful DREZ lesioning was
      significantly lower  than that from the intact DREZ and that from the injured
      DREZ before lesioning. CONCLUSIONS: The ESG power from the injured DREZ increases
      in patients with pain after brachial plexus avulsion compared with that of the
      intact DREZ; this increase is reduced by successful DREZ lesioning.

PMID- 22971503
TI  - Gender-specific normal levels of myocardial metabolites determined by localized
      1H-magnetic resonance spectroscopy.
AB  - OBJECTIVE: Gender-specific normal concentrations of myocardial metabolites and
      the differences that might exist between healthy males and females were measured
      in vivo using 1H-magnetic resonance spectroscopy (1H-MRS). METHODS: A total of
      100 healthy individuals (57 males, 43 females) were studied. Cardiac magnetic
      resonance imaging and localized 1H-MRS were used to localize the voxels and
      quantify myocardial metabolite concentrations, respectively, for each gender.
      RESULTS: A total of 14 participants were excluded because of motion and poor
      spectra, which meant that 86 participants (46 males, 40 females) were included in
      the final analysis. Spectral peaks were identified with chemical shifts
      corresponding to water, choline, creatine and triglyceride. Myocardial choline
      and creatine levels showed no statistically significant differences between males
      and females. Females had a significantly lower body mass index and body surface
      area compared with males, and a significantly higher concentration of myocardial
      triglycerides. CONCLUSIONS: Myocardial triglyceride concentration was shown to be
      related to gender, whereas myocardial creatine and choline concentrations were
      not gender-related.

PMID- 22971504
TI  - Paraoxonase-1 gene Q192R polymorphism and reactive oxygen metabolites.
AB  - OBJECTIVE: Paraoxonase-1 (PON1) is a high-density lipoprotein-associated
      antioxidant enzyme. The Q192R polymorphism of the PON1 gene can protect against
      oxidative conditions, but the relationship between Q192R polymorphism and
      oxidative stress-related markers remains controversial.  In this study, the
      diacron reactive oxygen metabolites (d-ROMs) test was used to investigate the
      relationship between Q192R polymorphism and oxidative stress-related markers in
      Japanese subjects. METHODS: Patients without a history of overt cardiovascular
      disease who were not receiving antioxidant  medication were enrolled in a cross
      sectional clinic-based study. An allele-specific polymerase chain reaction method
      was used to assess the PON1 Q192R polymorphism and compare the level of d-ROMs
      between genotypes. RESULTS: A total of 103 subjects were analysed. The RR
      genotype was  associated with a significantly lower level of d-ROMs than the RQ
      and QQ genotypes. After multivariate analysis the relationship between the
      genotypes and level of d-ROMs remained independently significant. CONCLUSIONS:
      The RR genotype may be protective against oxidative stress in cardiovascular 
      diseasefree Japanese subjects. In addition, the d-ROMs test can be useful for
      examining the role of the PON1 Q192R polymorphism under oxidative conditions.

PMID- 22971505
TI  - Optimal bent length of lightwand for intubation in adults: a randomized,
      prospective, comparative study.
AB  - OBJECTIVE: To evaluate the effect on intubation success of different bent lengths
      of a lightwand (a malleable illuminating stylet used for intubation), based on
      the patient's thyroid prominence-to-mandibular angle distance (TMD), thyroid
      prominence-to-incisor distance (TID) and gender. METHODS: This prospective,
      randomized, blinded study included patients undergoing elective surgery. In group
      A, the bent length was determined based on the patient's gender. In groups B and
      C, the bent length was calculated according to the patient's TMD or TID,
      respectively. Intubation success rate, time required for intubation,
      haemodynamics and complications postintubation were documented. RESULTS: A total
      of 246 patients were recruited and randomly assigned to one of the study groups.
      There were no significant differences in number of intubation attempts and
      success rate among the three groups. The mean time required for intubation was
      significantly shorter in group A than in the other groups. There were no major
      complications in any group. CONCLUSIONS: Gender-determined bent length was more
      suitable for lightwand-guided intubation than TID or TMD. For most patients, the
      optimal bent length was in the range of 6.0-6.9 cm.

PMID- 22971506
TI  - Hemoglobin decline in chemotherapy patients prior to and after policy changes
      affecting use of erythropoiesis-stimulating agents: 2006-2009.
AB  - OBJECTIVE: Since 2007, the use of erythropoiesis-stimulating agents (ESAs) to
      treat anemia in cancer patients receiving chemotherapy has been increasingly
      restricted in the USA. This study assessed hemoglobin (Hb) decline over time
      among chemotherapy patients. METHODS: Episodes of chemotherapy care were
      identified in a large US-oncology electronic medical record database; weekly Hb
      levels were computed in the first 8 weeks. Unadjusted and adjusted proportions of
      patient-weeks with Hb decline>1 g/dl (i.e. representing clinically significant
      decline) within 1 or 2 weeks were analyzed. RESULTS: Between 2006 and 2009,
      unadjusted proportions of patient-weeks with Hb decline>1 g/dl increased (1-week,
      from 12.7% to 14.9%; 2-week, from 19.3% to 26.3%). Adjusted 1-week proportions in
      2007 were similar to 2006, but increased in 2008 (odds ratio [OR] 1.135; 95%
      confidence intervals [CI] 1.067, 1.208) and in 2009 (OR 1.235; 95% CI 1.094,
      1.395). Adjusted 2-week proportions had the same pattern. CONCLUSIONS: Since
      restrictions on ESA use were introduced in the USA, more patients have
      experienced a clinically significant Hb decline after chemotherapy initiation.
      Initiating anemia therapy at the earliest indicated opportunity may help reduce
      the risk of such declines.

PMID- 22971507
TI  - Continuous subcutaneous insulin infusion in adult type 1 diabetes mellitus: data
      from a registry at the University Medical Centre Ljubljana, Slovenia.
AB  - OBJECTIVE: To evaluate the treatment indications, effectiveness and adverse
      events of continuous subcutaneous insulin infusion (CSII) in adults with type 1
      diabetes mellitus using data from a registry at the University Medical Centre
      Ljubljana, Ljubljana, Slovenia. METHODS: The registry included patients with type
      1 diabetes who had converted from multiple daily injection (MDI) to CSII.
      Patients with complete data sets covering a period of >=3 years were included in
      the study (n=184). Complications, glycaemic control and insulin dose during CSII
      were compared with data obtained during MDI. RESULTS: CSII resulted in
      significant reductions in glycosyated haemoglobin level and total daily insulin
      dose. The mean number of severe hypoglycaemic episodes during CSII was 0.17 per
      patient per year. CONCLUSIONS: Treatment of adults with type 1 diabetes mellitus
      by CSII can improve glycaemic control and reduce insulin requirements compared
      with MDI, however patient selection, education and continuous care are important
      parts of this therapy.

PMID- 22971508
TI  - Plasma adrenomedullin and subclinical cardiorenal syndrome in patients with type
      2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate whether plasma adrenomedullin is involved in the
      previously reported significant inverse correlation between left ventricular (LV)
      end-diastolic pressure (peak velocity of early transmitral flow/peak velocity of
      early diastolic mitral annular motion ratio [E/E' ]) and estimated glomerular
      filtration rate (eGFR) in patients with type 2 diabetes mellitus, mild-to
      moderate renal function impairment and LV relaxation impairment (E'<=7.1 cm/s).
      METHODS: Plasma adrenomedullin concentration, E/E' and eGFR were assessed in 82
      patients with type 2 diabetes. RESULTS: Plasma adrenomedullin concentration was
      positively correlated with eGFR in patients with or without LV relaxation
      impairment, and inversely correlated with E/E' in patients with LV relaxation
      impairment. Multivariate linear regression analysis supported a role for plasma
      adrenomedullin in the association between E/E' and eGFR. CONCLUSION: These
      results support the hypothesis that adrenomedullin modulates the interaction
      between the heart and kidneys in early subclinical cardiorenal syndrome in
      patients with type 2 diabetes mellitus.

PMID- 22971509
TI  - A morphological study of the left atrial appendage in chinese patients with
      atrial fibrillation.
AB  - OBJECTIVE: Using angiography, this study examined left atrial appendage (LAA)
      morphology in Chinese patients with atrial fibrillation (AF) or congenital atrial
      septal defects (ASD), to provide data that might aid the design of new LAA
      occluding devices to prevent cardioembolism and  stroke in patients with AF.
      METHODS: Patients with AF or ASD were enrolled. The LAA was visualized
      angiographically; its dimensions were measured and the emptying fraction was
      calculated. RESULTS: A total of 45 patients with AF and 30 patients with ASD were
      included in the study. LAA morphology  was classified into eight categories. The
      majority of patients with AF had tube-shaped LAAs with a single lobe; the most
      common LAA morphologies in patients with ASD were irregular or sphere-like, with
      multiple lobes. Patients with AF had significantly larger LAAs with significantly
      lower  emptying fractions compared with LAAs of patients with ASD. CONCLUSIONS:
      The LAA demonstrated considerable morpho logical variability in terms of its
      size, shape and number of lobes. The design of new occluding devices must take
      into account the size and shape of the LAA in patients with AF.

PMID- 22971510
TI  - Clinical Analysis of 50 Chinese Patients with Aqueous Misdirection Syndrome: a
      Retrospective Hospital-based Study.
AB  - OBJECTIVES: To evaluate the efficacy of treatments for aqueous misdirection
      syndrome and explore possible risk factors influencing prognosis. METHODS: Data
      including demographics, initial clinical characteristics and ocular outcomes at
      follow-up were collected for patients treated for aqueous misdirection syndrome.
      Main outcome measures were: best-corrected visual acuity (BCVA); intraocular
      pressure (IOP); number of antiglaucoma medications; recurrence; complications.
      RESULTS: Data were available for 50 patients (57 eyes). Final mean BCVA improved
      significantly and correlated with baseline BCVA (mean follow-up, 34.47+/-28.65
      months). Final mean IOP and mean number of antiglaucoma medications were
      significantly reduced. Treatment failure rates were higher in patients with
      significantly higher IOP at baseline and/or shorter axial length. Following pars
      plana vitrectomy (PPV), recurrence occurred in two of 10 pseudophakic and one of
      40 phakic eyes; complications were observed in 12/50 eyes (choroidal detachment,
      corneal decompensation, retinal detachment, vitreous haemorrhage, hyphaema).
      CONCLUSIONS: PPV and laser treatments, augmented by pharmacotherapy, were
      effective in treating aqueous misdirection syndrome. Surgical intervention should
      be undertaken early in eyes with higher baseline IOP and/or shorter axial length.
      Total vitrectomy-zonulectomy-iridectomy is a potential approach for recalcitrant
      cases.

PMID- 22971511
TI  - The characterization and management of Castleman's disease.
AB  - OBJECTIVE: Castleman's disease (CD) is a rare disorder of unknown aetiology
      characterized by lymph node enlargement. This study evaluated the clinical
      features, diagnosis and outcomes of surgical treatment in patients with CD.
      METHODS: The medical records of 10 patients with histologically  confirmed CD who
      underwent surgery between 2003 and 2008 were retrospectively reviewed. Study
      endpoints were survival and recurrence. RESULTS: The age of disease onset ranged
      from 11 to 63 years (median 38 years). Of the 10 patients included in the study,
      eight were diagnosed with localized  (unicentric) CD and two with multicentric
      CD. All eight patients with localized (unicentric) CD were asymptomatic.
      Histological evidence indicated the hyaline vascular form of CD in eight patients
      and the plasmacytic form in the remaining two patients. The primary treatment was
      complete surgical  resection in nine cases, and these patients were alive with no
      evidence of recurrence or exacerbation at the time of writing (June 2011).
      CONCLUSIONS: Localized (unicentric) CD is usually of the hyaline vascular form
      and complete surgical excision of the tumour allows full recovery in most  cases.

PMID- 22971512
TI  - Detection of KRAS mutations and their associations with clinicopathological
      features and survival in Chinese colorectal cancer patients.
AB  - OBJECTIVE: Mutation of the KRAS (v-Kiras2 Kirsten rat sarcoma viral oncogene
      homologue) gene plays an important role in colorectal tumorigenesis. This study
      examined associations between KRAS gene mutations and clinicopathological and
      survival data in Chinese patients  with colorectal cancer (CRC). METHODS: CRC
      patients were recruited for the detection of KRAS gene mutations using polymerase
      chain reaction and DNA sequencing. Data on clinicopathological features and
      survival times were collected. RESULTS: The study included 78 CRC patients. The
      overall  mutation frequency of the KRAS gene at codons 12 and 13 was 33.3%
      (26/78). KRAS gene mutations were significantly associated with poor tumour
      differentiation and liver metastasis. Patients with the wild-type KRAS gene had
      significantly higher median survival times than  patients with KRAS gene
      mutations (35.05 months versus 25.72 months). Those with KRAS gene mutations at
      codons 12 or 13 did not have significantly different median survival times (25.69
      months versus 20.67 months, respectively). CONCLUSIONS: These findings suggest
      that a high  frequency of KRAS gene mutations exists in Chinese patients with
      CRC, and that such mutations are associated with poor survival, tumour
      differentiation and liver metastasis in CRC patients.

PMID- 22971513
TI  - Laparoscopic versus open surgery for rectal cancer: a clinical comparative study.
AB  - OBJECTIVE: To compare short-term surgical outcomes and long-term survival
      following laparoscopic or open resection for rectal cancer. METHODS: A total of
      381 patients undergoing laparoscopic surgery and 276 undergoing open surgery for
      curative resection of rectal cancer were included. Long-term survival and peri-
      and postoperative data were retrospectively reviewed from a prospectively
      collected database. RESULTS: Surgical groups were comparable regarding age,
      gender, tumour stage and preoperative comorbidities. Laparascopic surgery was
      associated with significantly longer duration of surgery, less intraoperative
      blood loss and fewer postoperative infections than open surgery. Patients who
      underwent laparoscopic resection had significantly earlier recovery of
      gastrointestinal function than those who underwent open surgery. There were no
      significant between-group differences in number of lymph nodes excised, specimen
      length or distal margin. The 3- and 5-year survival rates and overall survival
      were similar in the two groups, and survival was not influenced by tumour
      location. CONCLUSION: Laparoscopic surgery can achieve the same oncological
      results as open resection in patients with rectal cancer, supporting its
      continued use in the management of this disease.

PMID- 22971514
TI  - Multifactor analysis on the outcomes of cervical spondylotic myelopathy with
      expansive open-door laminoplasty.
AB  - OBJECTIVES: To examine clinical outcomes following expansive open-door
      laminoplasty (EOLP) in the treatment of multilevel cervical spondylotic
      myelopathy (CSM) and the factors that influence these outcomes. METHODS: This
      retrospective analysis in CSM patients following EOLP investigated the
      relationship between recovery rate, based on the Japanese Orthopaedic Association
      (JOA) score, and the impact of age, duration of CSM, and axial symptoms,
      including the effect of EOLP on cervical curvature. RESULTS: In total, 79 CSM
      patients were included. Overall, the preand postoperative (1 year after surgery)
      mean+/-SD JOA scores were 9.6+/-1.4 and 14.7+/-1.9, respectively, indicating an
      improvement of 68.9%. Factors that were significantly related to 'excellent'
      (>=75%) or 'good' (>=50%-<75%) recovery rates included a high preoperative JOA
      score, short duration of CSM (<=12 months) and patient age<50 years. Significant
      reductions in cervical curvature angle were only observed in patients with axial
      symptoms. CONCLUSIONS: These results indicate that CSM should be treated early.
      The severity of CSM, the patient's age, cervical curvature angle, operation
      technique and axial symptoms play important roles in clinical outcomes.

PMID- 22971515
TI  - Primary paraganglioma of the lung: a case report and literature review.
AB  - Only 22 cases of primary pulmonary paraganglioma have been reported previously.
      This report presents a case of paraganglioma that arose in the lung of a 38-year
      old woman who presented with chest pain and paroxysmal cough with little sputum.
      Positron emission tomography-computed  tomography scan demonstrated two
      homogeneous masses in the left lower lobe accompanied by multiple mediastinal
      lymph node metastases. After resection, gross pathological examination confirmed
      two solid masses, which had a yellow-grey complexion and decreased blood supply
      and that invaded  the mediastinum. Immunohistochemical analysis confirmed the
      presence of several biological tumour markers. This is the first known report to
      describe the computed tomography imaging characteristics of a paraganglioma,
      thereby improving understanding of its morphological features and helping  in the
      differential diagnosis of lung tumours.

PMID- 22971516
TI  - Biophysical and computational fragment-based approaches to targeting protein
      protein interactions: applications in structure-guided drug discovery.
AB  - Drug discovery has classically targeted the active sites of enzymes or ligand
      binding sites of receptors and ion channels. In an attempt to improve selectivity
      of drug candidates, modulation of protein-protein interfaces (PPIs) of
      multiprotein complexes that mediate conformation or colocation of components of
      cell-regulatory pathways has become a focus of interest. However, PPIs in
      multiprotein systems continue to pose significant challenges, as they are
      generally large, flat and poor in distinguishing features, making the design of
      small molecule antagonists a difficult task. Nevertheless, encouragement has come
      from the recognition that a few amino acids - so-called hotspots - may contribute
      the majority of interaction-free energy. The challenges posed by protein-protein
      interactions have led to a wellspring of creative approaches, including
      proteomimetics, stapled alpha-helical peptides and a plethora of antibody
      inspired molecular designs. Here, we review a more generic approach: fragment
      based drug discovery. Fragments allow novel areas of chemical space to be
      explored more efficiently, but the initial hits have low affinity. This means
      that they will not normally disrupt PPIs, unless they are tethered, an approach
      that has been pioneered by Wells and co-workers. An alternative fragment-based
      approach is to stabilise the uncomplexed components of the multiprotein system in
      solution and employ conventional fragment-based screening. Here, we describe the
      current knowledge of the structures and properties of protein-protein
      interactions and the small molecules that can modulate them. We then describe the
      use of sensitive biophysical methods - nuclear magnetic resonance, X-ray
      crystallography, surface plasmon resonance, differential scanning fluorimetry or
      isothermal calorimetry - to screen and validate fragment binding. Fragment hits
      can subsequently be evolved into larger molecules with higher affinity and
      potency. These may provide new leads for drug candidates that target protein
      protein interactions and have therapeutic value.

PMID- 22971517
TI  - Contrasting effects of alpha-tocopheryl succinate on cisplatin- and etoposide
      induced apoptosis.
AB  - Targeting mitochondria is a promising strategy in tumor cell elimination. d-alpha
      tocopheryl succinate (alpha-TOS), a redox-silent analog of vitamin E, is a
      potentially powerful tool for fighting tumors by directly affecting mitochondria.
      However, when used at low concentrations it can suppress apoptosis induced by the
      conventionally used anticancer drug cisplatin. In cells treated with cisplatin,
      30MUM alpha-TOS prominently attenuated the manifestation of characteristic
      features of apoptosis - release of cytochrome c from mitochondria, caspase-3-like
      activity, and cleavage of poly(ADP-ribose) polymerase. In contrast, cell death
      induced by etoposide was not inhibited but rather stimulated by alpha-TOS. Thus,
      co-treatment with alpha-TOS and conventional antitumor drugs should be carried
      out with caution. 

PMID- 22971519
TI  - Primary angiitis of the central nervous system.
AB  - Despite the multiple areas of progress that have been made in our understanding
      of primary angiitis of the central nervous system (PACNS ), many challenges exist
      when facing this diagnosis. This review will address the clinical presentation,
      diagnosis and differential diagnosis of PACNS, with emphasis on the recognized
      advancement in the field. Appreciation of different mimics especially the
      recognition of reversible cerebral vasoconstriction syndromes (RCVS) as a major
      mimic will be addressed. Finally, approach to treatment will be summarized.

PMID- 22971518
TI  - First molecular characterization of Giardia duodenalis from goats in Malaysia.
AB  - In the present study, 310 faecal samples from goats from eight different farms in
      Malaysia were tested for the presence of Giardia using a PCR-coupled approach.
      The nested PCR for SSU amplified products of the expected size (~200 bp) from 21
      of 310 (6.8%) samples. Sixteen of these 21 products could be sequenced
      successfully and represented six distinct sequence types. Phylogenetic analysis
      of the SSU sequence data using Bayesian Inference (BI) identified Giardia
      assemblages A, B and E. The identification of the 'zoonotic' assemblages A and B
      suggests that Giardia-infected goats represent a possible reservoir for human
      giardiasis in Malaysia.

PMID- 22971520
TI  - Plasmons and optical excitations in graphene rings.
AB  - A simple semiclassical drude-like conductivity of graphene is employed to
      describe plasmon excitations of graphene in the ring structures. A quasi-static
      self-consistent integral equation approach is performed, allowing the calculation
      of all the plasmon modes with different angular momentum l. Among them only the
      dipole modes (l = 1) will couple out to the radiation modes, which in turn can be
      excited optically by the plane waves, and the excitation energies as a function
      of the ratio of the radius of the inner hole to that of the outer ring have also
      been investigated. It is demonstrated that the energy of symmetric modes will
      monotonically decrease as the ratio rises, and the energy of antisymmetric modes
      does not exhibit a monotonically increasing behavior as in a three-dimensional
      metallic ring, but first reduces and then increases. These predictions are tested
      by full-wave simulations using the optical conductivity of graphene that was
      obtained from the random phase approximation (RPA).

PMID- 22971521
TI  - Repeated low-dose intradermal allergen injection suppresses allergen-induced
      cutaneous late responses.
AB  - BACKGROUND: Subcutaneous immunotherapy with high-dose grass pollen was first
      described more than 100 years ago. This treatment suppresses allergen-induced
      cutaneous late responses, with lesser effects on early responses. In contrast,
      low-dose subcutaneous immunotherapy has not shown clinical benefit. Uncontrolled
      reports from the early 20th century describe low-dose allergen inoculation
      directly into the dermis, an immunologically active area containing abundant
      dendritic cells and lymphatics. OBJECTIVE: We sought to investigate the effect of
      low-dose intradermal grass pollen administration on cutaneous reactivity to
      allergen. METHODS: Thirty adults sensitized to grass and tree pollens were
      randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of
      grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per
      injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single
      intradermal injection at 10 weeks. At the end of the study, cutaneous early and
      late responses were measured after double-blind intradermal injection with grass
      and birch pollen. RESULTS: Participants who received 6 fortnightly intradermal
      grass pollen injections had markedly smaller cutaneous late responses to grass
      pollen than control subjects who received 2 injections separated by 10 weeks (P <
      .01) or a single injection (P < .001) and showed induction of grass pollen
      specific IgG antibodies. Suppression was observed whether late responses were
      measured on the arms or the back. However, early responses were equivalent in all
      groups. CONCLUSION: Low-dose intradermal allergen, like conventional subcutaneous
      high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in
      a manner that is allergen specific, systemic, and associated with induction of
      IgG antibodies.

PMID- 22971522
TI  - Pretreatment neutrophil-to-lymphocyte ratio in metastatic castration-resistant
      prostate cancer patients treated with ketoconazole: association with outcome and
      predictive nomogram.
AB  - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), an inflammation marker, is
      prognostic in several cancers. We assessed the association between the
      pretreatment NLR and outcome of patients with metastatic castration-resistant
      prostate cancer (mCRPC) treated with the CYP17 inhibitor ketoconazole. METHODS:
      This was an international, retrospective study of 156 mCRPC patients treated with
      ketoconazole. The independent effect of the pretreatment NLR and factors
      associated with treatment outcome were determined by multivariate analysis.
      RESULTS: Seventy-eight patients (50%) had a >=50% decline in prostate-specific
      antigen (PSA). The median progression-free survival (PFS) time was 8 months.
      Excluded from the analysis were 23 patients without available data on their NLR
      and those with a recent health event or treatment associated with a blood count
      change. Sixty-two patients (47%) had a pretreatment NLR >3. Risk factors
      associated with the PFS outcome were a pretreatment NLR >3 and PSA doubling time
      (PSADT) <3 months and a prior response to a gonadotropin-releasing hormone
      agonist of <24 months or to an antiandrogen of <6 months. The number of risk
      factors was used to form a predictive nomogram by patient categorization into
      favorable (zero or one factor), intermediate (two factors), and poor (three or
      four factors) risk groups. CONCLUSIONS: In mCRPC patients treated with
      ketoconazole, the pretreatment NLR and PSADT, and prior response to androgen
      deprivation therapy, may be associated with the PFS time and used to form a risk
      stratification predictive nomogram.

PMID- 22971523
TI  - Decreasing trend in mortality of chronic myelogenous leukemia patients after
      introduction of imatinib in Japan and the U.S.
AB  - PURPOSE: Although the impact of imatinib in improving survival outcomes in
      chronic myelogenous leukemia (CML) patients has been widely reported, its impact
      on mortality from CML has not been evaluated. A survival benefit demonstrated in
      clinical trials does not simply translate to a decrease in mortality. To evaluate
      the impact of imatinib on the public health, we estimated the age-standardized
      mortality rate of CML patients in Japan and the U.S. using vital statistics data
      for Japan and data from the Surveillance, Epidemiology, and End Results (SEER)
      Program of the National Cancer Institute for the U.S. PATIENTS AND METHODS: The
      period covered in this analysis is 1993-2008, during which 64,203 patients in
      Japan and 26,888 patients in nine registries in the U.S. died as a result of CML.
      We used joinpoint regression analysis to evaluate the significance of trends in
      mortality. RESULTS: Estimated age-standardized mortality rates decreased
      significantly in both countries after the availability of imatinib. The annual
      percent changes (95% confidence interval) in the U.S. were -12.3% (-14.8% to 
      9.7%) for men and -11.6% (-13.1% to -10.1%) for women. In Japan, these were 
      20.8% (-36.2% to -1.6%) for men and -15.6% (-18.8% to -12.2%) for women. The
      period of change in the mortality trend seems to correlate with the period in
      which imatinib appeared in the two countries. The CML mortality rate in 2008 was
      nearly 30% that of the 1993 level. CONCLUSION: This is one example of the advent
      of a single new drug changing the picture of a single disease, CML. These results
      may encourage further development of drugs based on the concept of molecular
      targeting.

PMID- 22971524
TI  - The antioxidant effect of carnosol in bovine aortic endothelial cells is mainly
      mediated via estrogen receptor alpha pathway.
AB  - Antioxidant action is critical for maintaining the normal cardiovascular function
      and vascular endothelial cell is an important target of estrogen action through
      estrogen receptor (ER) pathway. This study is carried out to explore the
      antioxidant effect of carnosol in bovine aortic endothelial cells (BAECs) via ER
      pathway. The ER subtype specific estrogenic effect of carnosol was further
      demonstrated by luciferase reporter gene assay in human embryonic kidney (HEK)
      293 cells. Carnosol was extracted from Chinese medicine Rosmarinus officinalis.
      ER positive BAECs were employed in cell proliferation assay and cell apoptosis
      tests. Oxidative stress by intracellular reactive oxygen species (ROS) were
      measured via 2'7'-dichlorofluorescein (DCF) production. ERalpha and ERbeta
      specific antagonists 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2
      piperidinylethoxy)phenol]-1H-pyrazole (MPP) and 4-[2-phenyl-5,7
      bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-yl]phenol (PHTPP) were employed
      as tools in the experiment. ER negative HEK 293 cells were employed in luciferase
      reporter gene assay. The results indicate that carnosol can effectively attenuate
      H(2)O(2) induced slowing down of cell growth and increasing of cell apoptosis. At
      the meantime, carnosol pretreating can also effectively reduce the H(2)O(2)
      induced intracellular ROS elevation in BAECs. ERalpha and ERbeta antagonist,
      especially ERalpha antagonist, can effectively decrease the above antioxidant
      effects of carnosol. The reporter gene analysis further demonstrates that the
      action of carnosol on inducing ERE dependent luciferase expression is realized
      via ER pathway. The conclusion is that carnosol can exert antioxidant effects
      towards oxidative stress induced by H(2)O(2) in BAECs. And such effects are
      realized via ER, especially ERalpha pathway. The results contribute to explain
      the mechanism of cardiovascular protective function of carnosol in postmenopausal
      women.

PMID- 22971526
TI  - Decreased levels of nuclear glucocorticoid receptor protein in the hippocampus of
      aged Long-Evans rats with cognitive impairment.
AB  - Previous studies using animal models of cognitive aging showed that hypothalamic
      pituitary-adrenal (HPA) responses to stress are impaired and glucocorticoid
      receptor (GR) mRNA is decreased in cognitively impaired aged rats, compared with
      those in young rats and cognitively unimpaired aged rats. Increased HPA activity
      is associated with the loss of hippocampal corticosteroid receptors. In the
      current investigation, GR expressions in the hippocampus were examined in young
      and aged male Long-Evans rats whose spatial memory was initially assessed on the
      Morris water maze task. We evaluated GR protein level in the hippocampus in young
      and aged rats characterized on the basis of the spatial task. In the hippocampus
      of aged rats with spatial memory impairments, GR protein level was decreased in
      the nucleus but not in the cytosol, and levels of glucocorticoid response
      elements binding activity was decreased. These results suggest that GR signaling
      is impaired in the hippocampus of rats with cognitive impairment. Impaired GR
      signaling may contribute to HPA axis dysfunction in aged rats and aged humans
      with cognitive impairment.

PMID- 22971525
TI  - An imaging-based stochastic model for simulation of tumour vasculature.
AB  - A mathematical model which reconstructs the structure of existing vasculature
      using patient-specific anatomical, functional and molecular imaging as input was
      developed. The vessel structure is modelled according to empirical vascular
      parameters, such as the mean vessel branching angle. The model is calibrated such
      that the resultant oxygen map modelled from the simulated microvasculature
      stochastically matches the input oxygen map to a high degree of accuracy (R(2) ~
      1). The calibrated model was successfully applied to preclinical imaging data.
      Starting from the anatomical vasculature image (obtained from contrast-enhanced
      computed tomography), a representative map of the complete vasculature was
      stochastically simulated as determined by the oxygen map (obtained from hypoxia
      [(64)Cu]Cu-ATSM positron emission tomography). The simulated microscopic
      vasculature and the calculated oxygenation map successfully represent the imaged
      hypoxia distribution (R(2) = 0.94). The model elicits the parameters required to
      simulate vasculature consistent with imaging and provides a key mathematical
      relationship relating the vessel volume to the tissue oxygen tension. Apart from
      providing an excellent framework for visualizing the imaging gap between the
      microscopic and macroscopic imagings, the model has the potential to be extended
      as a tool to study the dynamics between the tumour and the vasculature in a
      patient-specific manner and has an application in the simulation of anti
      angiogenic therapies.

PMID- 22971527
TI  - Correlation of plasma amino acid concentrations and chondroprotective effects of
      glucosamine and fish collagen peptide on the development of osteoarthritis.
AB  - We investigated the correlation of plasma amino acid concentrations and the
      effects of glucosamine and fish collagen peptide (FCP) on osteoarthritis (OA). OA
      was induced according to the rabbit anterior cruciate ligament transection (ACLT)
      model. After surgery, the rabbits were orally administered FCP (F group),
      glucosamine (G group) or both (FG group) for 4 weeks. The control group (C group)
      was not administered anything. Blood was collected before surgery (pre-ACLT) and
      before euthanasia (post-ACLT). Changes in the alanine, threonine and methionine
      concentrations were significant between pre- and post-ACLT. The correlation
      between the histological assessment and arginine concentration post-ACLT was
      significant. These findings indicate that measurement of plasma amino acids is
      useful for evaluation of the efficacy of intervention for OA.

PMID- 22971528
TI  - Cupping for treating neck pain in video display terminal (VDT) users: a
      randomized controlled pilot trial.
AB  - OBJECTIVES: This was a randomized controlled pilot trial to evaluate the
      effectiveness of cupping therapy for neck pain in video display terminal (VDT)
      workers. METHODS: Forty VDT workers with moderate to severe neck pain were
      recruited from May, 2011 to February, 2012. Participants were randomly allocated
      into one of the two interventions: 6 sessions of wet and dry cupping or heating
      pad application. The participants were offered an exercise program to perform
      during the participation period. A 0 to 100 numeric rating scale (NRS) for neck
      pain, measure yourself medical outcome profile 2 score (MYMOP2 score), cervical
      spine range of motion (C-spine ROM), neck disability index (NDI), the EuroQol
      health index (EQ-5D), short form stress response inventory (SRI-SF) and fatigue
      severity scale (FSS) were assessed at several points during a 7-week period.
      RESULTS: Compared with a heating pad, cupping was more effective in improving
      pain (adjusted NRS difference: -1.29 [95% CI -1.61, -0.97] at 3 weeks (p=0.025)
      and -1.16 [-1.48, -0.84] at 7 weeks (p=0.005)), neck function (adjusted NDI
      difference: -0.79 [-1.11, -0.47] at 3 (p=0.0039) and 7 weeks (p<0.0001)) and
      discomfort (adjusted MYMOP2 difference score: -0.72 [-1.04 to -0.40] at 3 weeks
      and -0.92 [-1.24, -0.60] at 7 weeks). Significant improvement in EQ-5D was
      observed at 7 weeks (1.0 [0.88, 1.0] with cupping and 0.91 [0.86, 0.91] with
      heating pad treatment, p=0.0054). Four participants reported mild adverse events
      of cupping. CONCLUSION: Two weeks of cupping therapy and an exercise program may
      be effective in reducing pain and improving neck function in VDT workers.

PMID- 22971529
TI  - Guidelines on obtaining consent for systemic anti-cancer therapy in adults.
AB  - This guideline, initially drawn up for use in the UK, is essentially based on
      ethical principles and should be applicable across other jurisdictions. The
      document specifically addresses the issues which surround obtaining consent from
      adults for the administration of systemic anti-cancer  therapy in the haemato
      oncology setting. Consenting to a treatment or procedure is a complex medical,
      ethical, and legal issue. The process of obtaining consent and the general steps
      that should be taken by the healthcare professional involved in obtaining consent
      from a patient are discussed,  and the potential legal and ethical pitfalls which
      can be encountered are outlined. Of fundamental importance are the requirements
      that agreement must be given voluntarily, based on adequate information, and the
      patient must have the ability to understand and retain the information given and 
      be in a position to use it in order to reach a decision. The consenting process
      should include an explanation of the expected outcomes and possible side effects
      of treatment even if these are unlikely to occur, and the nature of the
      consenting process undertaken should be clearly documented.  Obtaining consent in
      an emergency situation is also discussed, as is the process of consenting in
      individuals with impaired capacity or special needs. Withdrawal of consent and
      refusal of treatment are also considered.

PMID- 22971530
TI  - The effect of the combination of bisphosphonates and conventional chemotherapy on
      bone metabolic markers in multiple myeloma patients.
AB  - PURPOSE: Urinary N-terminal telopeptides of type I collagen (uNTX), serum bone
      alkaline phosphatase (sBAP) have been acknowledged in observing bone metastases
      of solid tumors. The paper is designed to study the value of clinical application
      of uNTX and sBAP in the treatment  of multiple myeloma (MM), as well as the
      action of bisphosphonates for osteolytic bone lesion. METHODOLOGY: Thirty-three
      MM cases were treated with bisphosphonates (hereinafter called clodronate therapy
      group) and 20 MM cases were treated with simple chemotherapy (hereinafter  called
      control group). uNTX and sBAP were tested during the courses of treatment three
      times (pretreatment, 3 months, and 6 months). uNTX was tested by enzyme-linked
      immunosorbent assay. sBAP was tested by chemiluminescence analysis. All the
      results were analyzed with t-test by using  SPSS 11.0. RESULTS: There were no
      significant differences between therapy and control groups: in uNTX (173.74 +/-
      14.55) and (129.79 +/- 12.13) MUg/l before treatment (P > 0.05). After 6 months
      there were significant differences  between them: (85.71 +/- 8.23) and (121.59 +/
      12.43) MUg/l (P < 0.05). And also there were significant differences among the
      courses in the therapy group. There were no significant differences between
      therapy and control groups in sBAP concentration:  (4.78 +/- 0.55) and (8.42 +/-
      1.32) MUg/l before treatment (P > 0.05). After 6 months there were significant
      differences between them: (16.01 +/- 0.52) and (9.62 +/- 1.29) MUg/l (P < 0.001).
      And also there were significant differences among the courses in the therapy
      group. CONCLUSION: uNTX and sBAP were important to measure the situation of the
      osteolytic bone lesion in MM. Bisphosphonates can significantly reduce bone
      degradation and metabolism, improve the  synthesis, which is valuable for the
      treatment of MM cases.

PMID- 22971531
TI  - Halofugine prevents cutaneous graft versus host disease by suppression of Th17
      differentiation.
AB  - Halofuginone, isolated from Dichroa febreifuga, is a potent inhibitor of skin
      collagen in chronic graft-versus-host disease (GVHD). To evaluate the effect of
      halofuginone on the development of cutaneous GVHD, we developed a murine model
      based on BALB/c (H-2d) as recipients with  transplantation of C57BL/6(H-2b) bone
      marrow plus splenocytes. Halofuginone or its vehicle dimethyl sulfoxide (DMSO)
      was given introperitoneally at a dose of 5 ug/mouse daily from one day before
      transplantation until 20 days post-transplantation. Halofuginone-treated
      recipients showed  only very mild appearance of cutaneous GVHD, whereas DMSO
      treated recipients rapidly showed manifestation of severe cutaneous GVHD,
      indicating a protective effect of halofuginone in cutaneous GVHD. After injected
      with halofuginone, we observed a decrease in the number of CD4(+) interleukin 
      (IL)-17(+) cells and a parallel increase in that of CD4(+) interferon (IFN)
      gamma(+) cells in peripheral blood. This shift between CD4(+) IL-17(+) cells and
      CD4(+) IFN-gamma(+) cells developed through modulation of cytokine profile 
      indicated by a marked increase in the levels of IFN-gamma, tumor necrosis factor
      (TNF)-alpha, and IL-6. The level of IL-10 was not changed obviously.
      Mechanistically, we demonstrate that severe tissue damage was associated with the
      production of IL-17 and expansion of CD4(+)IL-17(+)  cells during this disorder.
      Specific inhibition of Th17 differentiation by halofuginone reduced disease
      severity. Our results indicate a significant role of halofuginone in suppressing
      cutaneous GVHD, apparently through effect on inhibition of Th17 cells
      differentiation.

PMID- 22971532
TI  - Pitfalls and limitations of ZAP-70 detection in chronic lymphocytic leukemia.
AB  - Zeta-associated protein of 70 kDa (ZAP-70) is a tyrosine kinase that plays a role
      in signal transduction from the T-cell receptor. ZAP-70 is expressed in normal T
      cells and NK-cells. Increased expression of ZAP-70 has been identified in chronic
      lymphocytic leukemia (CLL). CLL patients  with increased ZAP-70 expression have
      significantly worse prognosis in terms of both progression-free survival and
      overall survival. There are several methods to quantify ZAP-70: polymerase chain
      reaction (PCR), immunoblotting, immunohistochemistry, and flow cytometry. Use of
      flow cytometry  for ZAP-70 detection seems to be advantageous as this technique
      enables us to assess the presence of ZAP-70 separately on CLL clone, T-cells, and
      NK-cells. On the other hand, detection of ZAP-70 by flow cytometry is
      substantially influenced by many variables. The principal drawback of flow 
      cytometry is the absence of consensus regarding selection of optimal anti-ZAP-70
      antibody, fluorochrome conjugate, the most reliable staining technique, and
      optimal positivity threshold. This article summarizes pitfalls of flow cytometric
      analysis of ZAP-70 in CLL.

PMID- 22971533
TI  - Aberration of p73 promoter methylation in de novo myelodysplastic syndrome.
AB  - p73, a tumor suppressor gene with significant homology to p53, is hypermethylated
      in a high percentage of NK-cell lymphoma and B-cell lymphomas patients. Given
      these data, we sought to study the role of p73 methylation in the pathogenesis of
      myelodysplastic syndromes (MDS).  In this study, the methylation status of the
      p73 gene promoter was analyzed by methylation-specific polymerase chain reaction
      (MS-PCR) in bone marrow (BM) samples from 135 adult patients with de novo MDS.
      The results of MS-PCR were confirmed by bisulfite sequencing. We found  that p73
      methylation was present in 37% (n = 50) of these cases and methylaiton was
      correlated significantly with World Health Organization (WHO) subtypes. Patients
      with advanced stages of WHO subtypes (30 vs. 59%, P = 0.002) exhibited a
      significantly  higher frequency of p73 methylation. Moreover, a decrease in
      transcription of p73 was accompanied by methylation (P = 0.032) and the
      decitabine treatment restored the expression of p73. The median survival of
      patients with p73 methylation was shorter  than that for patients without p73
      methylation (15 vs. >33 months, P = 0.002). A multivariate analysis also
      indicated that the p73 methylation status was the independent factor that
      impacted overall survival (OS) and leukemia-free survival (LFS). However,  we
      failed to find any significant association between p73 methylation and clinical
      responses to decitabine, a hypomethylating agent that was approved by the US Food
      and Drug Administration for the treatment of patients with MDS. In conclusion,
      p73 methylation is common in patients  with MDS and indicate poor prognosis. p73
      may be a therapeutic target in MDS.

PMID- 22971534
TI  - The clinical significance of circulating B cells secreting anti-glycoprotein
      IIb/IIIa antibody and platelet glycoprotein IIb/IIIa in patients with primary
      immune thrombocytopenia.
AB  - OBJECTIVES: The objective of the study is to evaluate the possible roles of the
      detection of circulating B cells secreting anti-glycoprotein IIb/IIIa antibody,
      platelet glycoprotein IIb/IIIa, and anti-glycoprotein IIb/IIIa antibody in the
      diagnosis of primary immune thrombocytopenia  (ITP) patients. METHODS:
      Circulating B cells secreting anti-glycoprotein IIb/IIIa antibody, platelet
      glycoprotein IIb/IIIa and anti-glycoprotein IIb/IIIa antibody in 64 patients with
      ITP, 33 non-ITP patients, and 32 controls were measured with enzyme-linked
      immunospot assay  (ELISPOT), monoclonal antibody immobilization of platelet
      antigens assay (MAIPA) and flow cytometic analysis (FCM), respectively. RESULTS:
      Compared with the controls and non-ITP patients, the frequency of circulating B
      cells secreting anti-glycoprotein IIb/IIIa antibody  was significantly increased,
      whereas the positive rate of platelet glycoprotein IIb/IIIa was significantly
      decreased (P < 0.05) in ITP patients, respectively. The sensitivities for the
      diagnosis of ITP of ELISPOT and FCM were 68.8% and 57.8%, and the specificities
      of 90.9%  and 90.9%, respectively. The sensitivities of ELISPOT and FCM were
      higher than MAIPA's sensitivity (39.1%) (P < 0.05). However, there was no
      apparent difference of the sensitivities of ELISPOT and FCM and the specificities
      of those three detections (MAIPA's specificity  was 81.8%) (P > 0.05).
      DISCUSSION: ELISPOT and FCM for detecting the circulating B cells secreting anti
      glycoprotein IIb/IIIa antibody and the platelet glycoprotein IIb/IIIa were as
      specific as that of MAIPA for assay of anti-glycoprotein IIb/IIIa antibody, but 
      ELISPOT and FCM had higher sensitivities. So ELISPOT and FCM were sensitive and
      specific for identifying patients with autoantibody-mediated thrombocytopenia and
      these should be used as diagnostic tests in clinic.

PMID- 22971535
TI  - Status of 25-hydroxyvitamin D deficiency and effect of vitamin D receptor gene
      polymorphisms on bone mineral density in thalassemia patients of North India.
AB  - BACKGROUND: Bone disease comprising of low bone mineral density (BMD), bone pain,
      and fractures is a characteristic feature of thalassemia. Vitamin D receptors
      (VDRs - FokI, TaqI, and Bsml) polymorphisms are closely related to low BMD at the
      lumbar  spine and hips which can be used as a useful genetic marker in predicting
      bone disease in these patients. AIM: To find out the status of VDRs gene
      polymorphisms and its effect on osteoporosis in thalassemia patients of North
      Indian origin. MATERIAL AND METHODS: BMD was measured in 40 beta-thalassemia
      major patients by dual-energy X-ray densitometry (DXA). Serum vitamin D levels
      were estimated by enzyme linked immunosorbant assay. VDR gene polymorphisms
      (FokI, TaqI, and BsmI) were analyzed by polymerase chain reaction restriction 
      fragment length polymorphism (PCR-RFLP) method. RESULTS: About 80.6% cases were
      found to be vitamin D deficient. Z score of BMD of lumbar spine and hips were 
      2.31 +/- 1.18 and -2.09 +/- 0.89. Osteoporotic lumbar spine was  observed in
      42.5% cases of thalassemia. A positive correlation of vitamin D level was found
      with Z score of BMD of lumbar spine (r = 0.398, P value = 0.027). Polymorphisms
      of FokI and BsmI were found significantly correlated with BMD of  lumbar spine.
      However, no association of BMD was observed with TaqI polymorphism. CONCLUSION:
      The present study showed a high prevalence of low BMD in thalassemia, suggesting
      that they should be targeted for DXA screening and osteoporosis prevention before
      permanent  end organ bone damage occurs. The VDR genotyping can be used as
      additional test in individuals who are susceptible to osteoporosis so that early
      preventive measurements can be taken.

PMID- 22971536
TI  - Correlation between bone mineral densitometry and liver/heart iron overload
      evaluated by quantitative T2* MRI.
AB  - BACKGROUND: Osteomalacia and osteoporosis are a common clinical problem in
      patients with beta thalassemia major. The purpose of this study is to assess the
      possible correlation of excess iron in liver and heart of beta thalassemia
      patient with bone mineral density (BMD). MATERIALS AND METHODS: We performed a
      prospective cross-sectional study on 80 patients with beta thalassemia major and
      inermedia. The patients were stratified into normal BMD and those with abnormal
      BMD test based on T-score. All patients underwent magnetic resonance imaging 
      examinations of heart and liver. Multi-echo fast gradient-echo sequence was used
      and T2* values were calculated based on the Royal Brompton Hospital protocol.
      Correlations between T2* values in heart and liver as well as serum ferritin
      levels with femoral and lumbar BMD were investigated. RESULTS: There were no
      significant differences between patients with and without osteopenia or
      osteoporosis with respect to age and sex. Patients with abnormal BMD had lower
      T2* values in the heart. Serum ferritin and heart iron load (based on T2*) were
      negatively correlated  with BMD. CONCLUSION: Serum ferritin and heart iron
      content are good indicators of BMD in patients with beta thalassemia major and
      intermedia.

PMID- 22971537
TI  - Screening of blood donors for erythrocyte alloantibodies.
AB  - OBJECTIVE: To assess the prevalence of the anti-red blood cell antibodies in the
      donor population of Delhi. METHODS: This prospective study was conducted in
      Regional Blood Transfusion Centre (RBTC), Lady Hardinge Medical College (LHMC)
      and associated hospitals  from March 2010 to March 2011. Antibody screening of
      all donor serum/plasma was performed as routine immunohaematological procedure.
      Any positive sera were further investigated to identify the specificity of
      irregular erythrocyte antibody by commercially available red cell panel (ID-Dia
      Panel,  Diamed-ID Microtyping System). The titres and thermal amplitude of the
      identified antibodies were evaluated. RESULTS: A total of 7756 donors were
      screened, of which 7648 donors were males (98.6%) and 108 were females (1.4%).
      The maximum number of donors belonged to age group  of 26-30 years. A total of
      four donors showed presence of alloantibodies in their serum (0.05%). On antibody
      identification, two of them were anti-C, one was anti-Lewis(a) antibody and one
      was autoantibody. DISCUSSION: This study was conducted to highlight  the
      significance of detecting irregular erythrocyte antibodies in healthy donors.

PMID- 22971538
TI  - Concurrent audit of fresh frozen plasma: experience of a tertiary care hospital.
AB  - Fresh frozen plasma (FFP) transfusion is among the highest risk of all blood
      component transfusions and also the most inappropriately used blood component.
      All these factors have impact on safety, economy, and work burden. OBJECTIVE: To
      assess the utilization of FFP  in a tertiary care hospital. METHODS: Concurrent
      audit was conducted manually over the period of 4 months from April 2010 to July
      2010. Patient's age, sex, clinical diagnosis, indication for FFP transfusion, and
      coagulation profile were noted. Data were analysed and episodes  of transfusion
      were divided into appropriate and inappropriate. Requests were further classified
      according to the requesting department, clinical diagnosis, and coagulation
      profile. RESULTS: A total of 1763 units of FFP were transfused to 560 patients in
      877 episodes of  requisition. Out of 877 episodes, about 686 (78.2%) requests
      were found to be inappropriate. Highest number of FFP requisitions was received
      from department of paediatrics and paediatric surgery (580 episodes). Most
      inappropriate requests were received from the department of orthopaedics (88.9%) 
      and paediatrics (80.17%). The most common indication for FFP transfusion was
      surgical/traumatic bleeding/massive transfusion (40.9%) in which 68.5% requests
      were inappropriate. Out of 686 inappropriate episodes, the most common cause was
      in setting of normal or mildly altered coagulation profile  irrespective of
      bleeding status of patient. DISCUSSION: Inadvertent use of FFP is a major problem
      and guidelines are not strictly adhered to. Concurrent audit of FFP use needs to
      be done to make appropriate interventions to prevent misuse of this valuable
      commodity.

PMID- 22971539
TI  - Dosimetric verification of radiotherapy treatment planning systems in Serbia:
      national audit.
AB  - BACKGROUND: Independent external audits play an important role in quality
      assurance programme in radiation oncology. The audit supported by the IAEA in
      Serbia was designed to review the whole chain of activities in 3D conformal
      radiotherapy (3D-CRT) workflow, from patient data acquisition to treatment
      planning and dose delivery. The audit was based on the IAEA recommendations and
      focused on dosimetry part of the treatment planning and delivery processes.
      METHODS: The audit was conducted in three radiotherapy departments of Serbia. An
      anthropomorphic phantom was scanned with a computed tomography unit (CT) and
      treatment plans for eight different test cases involving various beam
      configurations suggested by the IAEA were prepared on local treatment planning
      systems (TPSs). The phantom was irradiated following the treatment plans for
      these test cases and doses in specific points were measured with an ionization
      chamber. The differences between the measured and calculated doses were reported.
      RESULTS: The measurements were conducted for different photon beam energies and
      TPS calculation algorithms. The deviation between the measured and calculated
      values for all test cases made with advanced algorithms were within the agreement
      criteria, while the larger deviations were observed for simpler algorithms. The
      number of measurements with results outside the agreement criteria increased with
      the increase of the beam energy and decreased with TPS calculation algorithm
      sophistication. Also, a few errors in the basic dosimetry data in TPS were
      detected and corrected. CONCLUSIONS: The audit helped the users to better
      understand the operational features and limitations of their TPSs and resulted in
      increased confidence in dose calculation accuracy using TPSs. The audit results
      indicated the shortcomings of simpler algorithms for the test cases performed
      and, therefore the transition to more advanced algorithms is highly desirable.

PMID- 22971540
TI  - Significant reduction of acute cardiac allograft rejection by selective janus
      kinase-1/3 inhibition using R507 and R545.
AB  - BACKGROUND: Selective inhibition of lymphocyte activation through abrogation of
      signal 3-cytokine transduction emerges as a new strategy for immunosuppression.
      This is the first report on the novel Janus kinase (JAK)1/3 inhibitors R507 and
      R545 for prevention of acute allograft rejection. METHODS: Pharmacokinetic and in
      vitro enzyme inhibition assays were performed to characterize the drugs.
      Heterotopic Brown Norway-Lewis heart transplantations were performed to study
      acute cardiac allograft rejection, graft survival, suppression of cellular host
      responsiveness, and antibody production. Therapeutic and subtherapeutic doses of
      R507 (60 and 15 mg/kg 2 times per day) and R545 (20 and 5 mg/kg 2 times per day)
      were compared with those of tacrolimus (Tac; 4 and 1 mg/kg once per day).
      RESULTS: Plasma levels of R507 and R545 were sustained high for several hours.
      Cell-based enzyme assays showed selective inhibition of JAK1/3-dependent pathways
      with 20-fold or greater selectivity over JAK2 and Tyrosine kinase 2 kinases.
      After heart transplantation, both JAK1/3 inhibitors reduced early mononuclear
      graft infiltration, even significantly more potent than Tac. Intragraft
      interferon-gamma release was significantly reduced by R507 and R545, and for
      interleukin-10 suppression, they were even significantly more potent than Tac.
      Both JAK1/3 inhibitors and Tac were similarly effective in reducing the host Th1
      and Th2, but not Th17, responsiveness and similarly prevented donor-specific
      immunoglobulin M antibody production. Subtherapeutic and therapeutic R507 and
      R545 doses prolonged the mean graft survival and were similarly effective as 1
      and 4 mg/kg Tac, respectively. In combination regimens, however, only R507 showed
      highly beneficial synergistic drug interactions with Tac. CONCLUSIONS: Both R507
      and R545 are potent novel immunosuppressants with favorable pharmacokinetics and
      high JAK1/3 selectivity, but only R507 synergistically interacts with Tac.

PMID- 22971541
TI  - Repeated orexin 1 receptor antagonism effects on cocaine seeking in rats.
AB  - The orexin/hypocretin system has been implicated in multiple phases of drug
      addiction. Acute orexin receptor blockade with the orexin-1 receptor (OX1R)
      antagonist, SB-334867, has been found to reduce cocaine seeking after cocaine
      self-administration. As repeated drug dosing can have differential effects and is
      more clinically relevant than acute dosing, in the current study we examined the
      effects of repeated SB-334867 on cocaine self-administration, extinction, and
      reinstatement to cocaine seeking in Sprague-Dawley rats. We found that repeated
      SB-334867 (10 mg/kg/day) had no effect on established cocaine self
      administration. Repeated SB-334867 (both 10 and 20 mg/kg) attenuated cocaine
      seeking during extinction; however, this effect was only observed when animals
      had no prior experience with SB-334867 and when SB-334867 was administered prior
      to, but not after, daily extinction sessions. Notably, daily treatment with SB
      334867 (10 mg/kg) during extinction increased subsequent cue-induced
      reinstatement, whereas repeated SB-334867 (20 mg/kg) administration during
      extinction enabled acute SB-334867 to reduce cue-induced reinstatement. Repeated
      SB-334867 treatment (10 or 20 mg/kg) failed to affect reinstatement induced by
      priming injections of cocaine (10 mg/kg). These results show that repeated
      inhibition of OX1R-mediated signaling exerts a lasting and specific role in
      mediating environmentally activated cocaine seeking.

PMID- 22971544
TI  - Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and
      provides functional protection in the 6-hydroxydopamine-lesioned rat model of
      Parkinson's disease.
AB  - Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic
      neurons against a range of toxic insults in vitro, through activation of
      fibroblast growth factor receptor 1 (FGFR1). This study set out to examine
      whether FGF-20 also displayed protective efficacy in the unilateral, 6
      hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies
      demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was
      expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with
      previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH
      positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH
      staining was also demonstrated in the substantia nigra pars compacta (SNpc) of
      naive adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal
      tract, supra-nigral infusion of FGF-20 (2.5 MUg/day) for 6 days post-lesion gave
      significant protection (~40%) against the loss of TH-positive cells in the SNpc
      and the loss of striatal TH immunoreactivity. This protection of the
      nigrostriatal tract was accompanied by a significant preservation of gross
      locomotion and fine motor movements and reversal of apomorphine-induced
      contraversive rotations, although forelimb akinesia, assessed using cylinder test
      reaching, was not improved. These results support a role for FGF-20 in preserving
      dopamine neuron integrity and some aspects of motor function in a rodent model of
      Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in
      this disease.

PMID- 22971543
TI  - Muscarinic receptors acting at pre- and post-synaptic sites differentially
      regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal
      neurons.
AB  - Muscarinic receptors, activated by acetylcholine, play critical roles in the
      functional regulation of medium spiny neurons in the striatum. However, the
      muscarinic receptor signaling pathways are not fully elucidated due to their
      complexity. In this study, we investigated the function of muscarinic receptors
      in the striatum by monitoring DARPP-32 (dopamine- and cAMP-regulated
      phosphoprotein of M(r) 32 kDa) phosphorylation at Thr34 (the PKA-site) using
      mouse striatal slices. Treatment of slices with a non-selective muscarinic
      receptor agonist, oxotremorine (10 MUM), rapidly and transiently increased DARPP
      32 phosphorylation. The increase in DARPP-32 phosphorylation was completely
      abolished either by a dopamine D(1) receptor antagonist (SCH23390), tetrodotoxin,
      genetic deletion of M5 receptors, muscarinic toxins for M1 and M4 receptors, or 6
      hydroxydopamine lesioning of dopaminergic neurons, whereas it was enhanced by
      nicotine. Analysis in D(1)-DARPP-32-Flag/D(2)-DARPP-32-Myc transgenic mice
      revealed that oxotremorine increases DARPP-32 phosphorylation selectively in D(1)
      type/striatonigral, but not in D(2)-type/striatopallidal, neurons. When D(1) and
      D(2) receptors were blocked by selective antagonists to exclude the effects of
      released dopamine, oxotremorine increased DARPP-32 Thr34 phosphorylation only in
      D(2)-type/striatopallidal neurons. This increase required activation of M1
      receptors and was dependent upon adenosine A(2A) receptor activity. The results
      demonstrate that muscarinic receptors, especially M5 receptors, act at
      presynaptic dopaminergic terminals, regulate the release of dopamine in
      cooperation with nicotinic receptors, and activate D(1) receptor/DARPP-32
      signaling in the striatonigral neurons. Muscarinic M1 receptors expressed in
      striatopallidal neurons interact with adenosine A(2A) receptors and activate
      DARPP-32 signaling.

PMID- 22971542
TI  - Altered cerebellar organization and function in monoamine oxidase A hypomorphic
      mice.
AB  - Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain
      serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We
      recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO
      A(Neo)), featuring elevated monoamine levels, social deficits and perseverative
      behaviors as well as morphological changes in the basolateral amygdala and
      orbitofrontal cortex. Here we showed that MAO-A(Neo) mice displayed deficits in
      motor control, manifested as subtle disturbances in gait, motor coordination, and
      balance. Furthermore, magnetic resonance imaging of the cerebellum revealed
      morphological changes and a moderate reduction in the cerebellar size of MAO
      A(Neo) mice compared to wild type (WT) mice. Histological and immunohistochemical
      analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed
      abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje
      cell count and their dendritic density in MAO-A(Neo) mice compared to WT. Our
      current findings suggest that congenitally low MAO-A activity leads to abnormal
      development of the cerebellum.

PMID- 22971545
TI  - Uremia causes premature ageing of the T cell compartment in end-stage renal
      disease patients.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients treated with renal
      replacement therapy (RRT) have premature immunologically aged T cells which may
      underlie uremia-associated immune dysfunction. The aim of this study was to
      investigate whether uremia was able to induce premature ageing of the T cell
      compartment. For this purpose, we examined the degree of premature immunological
      T cell ageing by examining the T cell differentiation status, thymic output via T
      cell receptor excision circle (TREC) content and proliferative history via
      relative telomere length in ESRD patients not on RRT. RESULTS: Compared to
      healthy controls, these patients already had a lower TREC content and an
      increased T cell differentiation accompanied by shorter telomeres. RRT was able
      to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length
      in young dialysis patients. An increased differentiation status of memory CD4+ T
      cells was also noted in young dialysis patients. CONCLUSION: Based on these
      results we can conclude that uremia already causes premature immunological ageing
      of the T cell system and RRT further increases immunological ageing of the CD8+ T
      cell compartment in particular in young ESRD patients.

PMID- 22971546
TI  - The electronic structure of RbTiOPO4 and the effects of the A-site cation
      substitution in KTiOPO4-family crystals.
AB  - The electronic structure of RbTiOPO(4) has been investigated with x-ray
      photoemission spectroscopy. Detailed photoemission spectra of the element core
      levels have been recorded under excitation by nonmonochromatic Al Kalpha
      radiation (1486.6 eV). The chemical bonding parameters are compared to those
      reported for complex titanates and phosphates. The band structures of KTiOPO(4),
      RbTiOPO(4), K(0.535)R(0.465)TiOPO(4) and TlTiOPO(4) have been calculated by ab
      initio methods and compared to available experimental results. It is found that
      the band structure of KTP-type phosphate crystals is weakly dependent on the
      nature of the A-site (A=K, Rb, Tl) element.

PMID- 22971547
TI  - Reward modulates the neural dynamics of early visual category processing.
AB  - Converging evidence suggests that visual brain regions are part of a widespread
      network that signals forthcoming reward. However, the precise temporal dynamics
      underlying the interaction between reward and visual information processing
      remain unclear. To further investigate this issue, we used magnetoencephalography
      (MEG) in combination with two versions of a face/scene discrimination task
      followed by a recognition memory test. In experiment 1, the distinction between
      faces and scenes was associated with monetary reward prospect, whereas in
      experiment 2 subjects distinguished between both categories in the absence of
      reward. In both experiments characteristic neural category effects (i.e.,
      differences between faces and scenes) were observed in the event-related magnetic
      fields (ERF) at ~100 ms (M100) and ~170 ms (M170) after stimulus onset.
      Importantly, both ERF components (M100 and M170) were amplified in the context of
      reward (i.e., experiment 1) and this interaction could be source localized to the
      lateral occipital cortex (~100 ms) and fusiform gyrus (~170 ms). Furthermore,
      neural effects of reward prediction emerged over frontal sensors at ~300 ms after
      stimulus onset which reliably correlated with subsequent recognition memory
      performance. These results demonstrate that reward motivation can modulate early
      neural computations of complex visual information, possibly by tuning sensory
      neurons within the visual cortex.

PMID- 22971548
TI  - Brain perfusion SPECT in the mouse: normal pattern according to gender and age.
AB  - Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal
      activity and a parameter of primary interest in the diagnosis of many diseases.
      The increasing use of mouse models spawns the demand for in vivo measurement of
      rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at
      adequate sensitivity and is therefore a promising tool for imaging the mouse
      brain. This study evaluates the feasibility of mouse brain perfusion SPECT and
      assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age
      and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD
      using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake
      pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were
      performed in 18 juvenile mice aged 7.5 +/- 1.5weeks, and in the same animals at
      young adulthood, 19.1 +/- 4.0 weeks (nanoSPECT/CTplus, general purpose mouse
      apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an
      adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT
      images were stereotactically normalized using SPM8 and a custom made, left-right
      symmetric HMPAO template in atlas space. For testing lateral asymmetry, each
      SPECT was left-right flipped prior to stereotactical normalization. Flipped and
      unflipped SPECTs were compared by paired testing. Peak brain uptake was similar
      for ECD and HMPAO: 1.8 +/- 0.2 and 2.1 +/- 0.6 %ID (p=0.357). Washout after the
      peak was much faster for ECD than for HMPAO: 24 +/- 7min vs. 4.6 +/- 1.7h
      (p=0.001). The general linear model for repeated measures with gender as an
      intersubject factor revealed an increase in relative HMPAO uptake with age in the
      neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the
      midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left
      hemisphere, was detected primarily in the neocortex, both at juvenile age
      (asymmetry index AI=2.7 +/- 1.7%, p=0.000) and at young adult age (AI=2.4 +/-
      1.7%, p=0.000). Gender had no effect on asymmetry. Voxel-wise testing confirmed
      the ROI-based findings. In conclusion, high-resolution HMPAO SPECT is a promising
      technique for measuring rCBF in preclinical research. It indicates lateral
      asymmetry of rCBF in the mouse brain as well as age-related changes during late
      maturation. ECD is not suitable as tracer for brain SPECT in the mouse because of
      its fast clearance from tissue indicating an interspecies difference in esterase
      activity between mice and humans.

PMID- 22971549
TI  - Calibrated BOLD using direct measurement of changes in venous oxygenation.
AB  - Calibration of the BOLD signal is potentially of great value in providing a
      closer measure of the underlying changes in brain function related to neuronal
      activity than the BOLD signal alone, but current approaches rely on an assumed
      relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF).
      This is poorly characterised in humans and does not reflect the predominantly
      venous nature of BOLD contrast, whilst this relationship may vary across brain
      regions and depend on the structure of the local vascular bed. This work
      demonstrates a new approach to BOLD calibration which does not require an
      assumption about the relationship between cerebral blood volume and cerebral
      blood flow. This method involves repeating the same stimulus both at normoxia and
      hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in
      venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on
      venous blood oxygenation has to be calculated, which requires an estimate of
      basal oxygen extraction fraction, and this can be estimated from the phase as an
      alternative to using a literature estimate. Additional measurement of the
      relative change in CBF, combined with the blood oxygenation change can be used to
      calculate the relative change in CMRO(2) due to the stimulus. CMRO(2) changes of
      18 +/- 8% in response to a motor task were measured without requiring the
      assumption of a CBV/CBF coupling relationship, and are in agreement with previous
      approaches.

PMID- 22971550
TI  - Epidemiology and predictors of end-stage renal disease in Taiwanese children with
      idiopathic nephrotic syndrome.
AB  - BACKGROUND: The incidence of idiopathic nephrotic syndrome (INS) varies among
      countries, with Asia reporting a higher incidence in comparison with Western
      countries. We investigated the epidemiologic features of INS and attempted to
      identify factors that predispose individuals to develop end-stage renal disease
      (ESRD). METHODS: Claims data from the Taiwanese National Health Insurance program
      from 1996 to 2008 were used to investigate the epidemiologic features and
      clinical variables of INS (International Classification of Diseases, Ninth
      Revision, Clinical Modification code, 581) in children younger than 18 years.
      RESULTS: We enrolled 4083 children (male-female ratio, 1.91:1). During the 13
      years of observation, annual incidence decreased from 9.91 to 3.36 per 100 000
      children. Annual number of hospital admissions progressively decreased during the
      first 3 years after diagnosis. At 3.14 +/- 2.77 years after INS onset, ESRD had
      developed in 145 (3.6%) children. Independent predictors of ESRD included older
      age at onset, acute renal failure (ARF), hypertensive encephalopathy, and a
      histologic subtype with focal segmental glomerulosclerosis (FSGS). CONCLUSIONS:
      Pediatric INS in Taiwan was more frequent in boys. Unlike India, the current
      incidence of pediatric INS in Taiwan is very similar to that reported in Western
      studies. Older age at disease onset, ARF, hypertensive encephalopathy, and FSGS
      on biopsy are important predictors of poor renal outcome.

PMID- 22971551
TI  - Specific types of family support and adolescent non-school physical activity
      levels.
AB  - In a sample of 291 adolescents (mean age 13 yr), seven psychosocial factors,
      including family support, were examined in relation to accelerometry-derived
      physical activity (PA) measured after school and during the weekend. Gender
      specific stepwise linear regression analyses determined which combinations of
      factors explained the variance in nonschool moderate to vigorous PA and nonschool
      total PA after adjusting for % BF, age, and maturity (p <= 0.05). Being praised
      by a family member and % BF explained 13% of the variance in female nonschool
      MVPA, while being praised and maturity explained 13% of the variance in nonschool
      total PA. Having a family member watch him participate, % BF, and age explained
      11.5% of the variance in male nonschool MVPA, while having a family member
      participate with him explained 6.4% of the variance in nonschool total PA.
      Despite adolescents' growing independence, family support continues to influence
      PA levels.

PMID- 22971552
TI  - The influence of maturation on the oxygen uptake efficiency slope.
AB  - This study examined the influence of maturation on the oxygen uptake efficiency
      slope (OUES) in healthy male subjects. Seventy-six healthy male subjects (8-27
      yr) were divided into groups based on maturation status: prepubertal (PP),
      midpubertal (MP), late-pubertal (LP), and young-adult (YA) males. Puberty status
      was determined by physical examination. Subjects performed a graded exercise test
      on a cycle ergometer to determine OUES. Group differences were assessed using a
      one-way ANOVA. OUES values (VO(2)L.min(-1)/log(10)V(E)L.min(-1)) were lower in PP
      and MP compared with LP and YA (p < .05). When OUES was expressed relative to
      body mass (VO(2)mL.kg-1.min(-1)/log(10)V(E)mL.kg(-1).min(-1)) differences between
      groups reversed whereby PP and MP had higher mass relative OUES values compared
      with LP and YA (p < .05). Adjusting OUES by measures of body mass failed to
      eliminate differences across maturational groups. This suggests that qualitative
      factors, perhaps related to oxidative metabolism, account for the responses
      observed in this study.

PMID- 22971553
TI  - Using the oxygen uptake efficiency slope as an indicator of cardiorespiratory
      fitness in the obese pediatric population.
AB  - The aim of the current study was to investigate the relationship between the
      Oxygen Uptake Efficiency Slope (OUES) and traditional measures of
      cardiorespiratory function in an overweight/obese pediatric sample. Maximal
      treadmill exercise testing with indirect calorimetry was completed on 56 obese
      children aged 7-18 years. Maximal OUES, submaximal OUES, VO(2peak), VE(peak), and
      ventilatory threshold (VT) were determined. In line with comparable research in
      healthy-weight samples, maximal and submaximal OUES were both correlated with
      VO(2peak), VE(peak), and VT (r(2)= 0.44-0.91) in the obese pediatric sample.
      Correlations were also found with anthropometric variables, including height
      (cm), body surface area (m(2)), body mass (kg), and fat free mass (kg). In
      comparing our data to a published sample of healthy weight children, maximal and
      submaximal exercise OUES were both higher in our obese sample. However, when we
      adjusted for any of body mass (kg), BSA (m(2)), or FFM (kg) the obese children
      were found to be less efficient. The results of this study suggest the use of
      OUES to be an appropriate measure of efficiency of ventilation and
      cardiorespiratory function in obese children, while also showing that our sample
      of obese children were less efficient on a per kilogram basis when compared with
      their healthy weight peers.

PMID- 22971554
TI  - Bicycling to school during the transition from childhood into adolescence: a six
      year longitudinal study.
AB  - Little is known about bicycling to school as children age. At baseline (2002)
      self-report data from 1070 children were gathered (51.9% boys; mean age: 10
      years).The measurements were repeated in 2003 (n = 1039), 2004 (n = 907), 2005 (n
      = 549) and 2008 (n = 515). The rates of children bicycling to school
      significantly varied across time points from 46% at the age of ten, 69% at the
      age of 11, 83% at the age of 12, 70% at the age of 13 toward 78% at the age of
      16. Starting from the age of 11, the average duration of time spent bicycling to
      school significantly increased over time. According to multilevel regression
      analyses 13.6% of the variance in rates of bicycling to school was situated at
      the school level, 39.6% at the pupil level and 46.7% at the measurement level.
      The differences in rates and durations across time points were independent from
      gender, BMI, SES and having siblings. Pupils engaging in bicycling to school at
      younger ages had a higher change of engaging in bicycling to school at 16 years
      old (ORs: 2.69-7.61; ICC bicycling rates: 0.46, ICC bicycling durations: 0.82).
      This finding emphasizes the need for promoting bicycling to school at young age.

PMID- 22971555
TI  - Use of an open-loop system to increase physical activity.
AB  - This study evaluated the effectiveness of an open-loop system that reinforces
      physical activity with TV watching to increase children's physical activity.
      Nonoverweight, sedentary boys and girls (8-12 y) were randomized to a group that
      received feedback of activity counts + reinforcement for physical activity by
      providing access to television (F+R, n = 20); or to feedback, no reinforcement
      (Feedback, n = 20) or no feedback, no reinforcement control (Control, n = 21)
      groups. Children wore an accelerometer with a count display for 4-months with a 1
      year follow-up. F+R reduced TV by 68 min/day and TV time was lower than the
      Feedback (p < .005) and Control (p < .002) groups. TV time of F+R remained 31 min
      lower (p < .02) than baseline at 1-year. F+R had a 44% increase in physical
      activity, which was greater than the feedback (p < .04) and control (p < .01)
      groups. An open-loop system decreases TV viewing and increases physical activity
      of children for 4-months. TV of the F+R group remained lower at 12 months,
      suggesting a reduction in screen-time habits.

PMID- 22971556
TI  - A steps/minute value for moderate intensity physical activity in adolescent
      females.
AB  - The number of steps/minute (i.e., cadence) that equates to moderate intensity in
      adolescents is not known. To that end, 31 adolescent females walked on a
      treadmill at 5 different speeds while wearing an ActivPAL accelerometer and
      oxygen uptake was recorded by indirect calorimetry. The relationship between
      metabolic equivalents (METs) and cadence was explored using 3 different
      analytical approaches. Cadence was a significant predictor of METs (r = .70; p <
      .001). Moderate intensity (3 METs) corresponded to 94 or 114 steps/minute based
      on the mixed model and ROC analysis, respectively. These two values, and a
      practical value of 100 steps/minute, were cross-validated on an independent
      sample of 33 adolescent females during over-ground walking at 3 speeds. The
      sensitivity and specificity of each value correctly identifying 3 METs were 98.5%
      and 87.2% for 94 steps/minute, 72.9% and 98.8 for 114 steps/minute and 96.5% and
      95.7% for 100 steps/minute. Compromising on a single cadence of 100 steps/minute
      would be a practical value that approximates moderate intensity in adolescent
      females and can be used for physical activity interpretation and promotion.

PMID- 22971557
TI  - Front crawl technical characterization of 11- to 13-year- old swimmers.
AB  - Our aim was to characterize front crawl swimming performed at very high intensity
      by young practitioners. 114 swimmers 11-13 years old performed 25 m front crawl
      swimming at 50 m pace. Two underwater cameras was used to assess general
      biomechanical parameters (velocity, stroke rate, stroke length and stroke index)
      and interarm coordination (Index of Coordination), being also identified each
      front crawl stroke phase. Swimmers presented lower values in all biomechanical
      parameters than data presented in studies conducted with older swimmers, having
      the postpubertal group closest values to adult literature due to their superior
      anthropometric and maturational characteristics. Boys showed higher velocity and
      stroke index than girls (as reported for elite swimmers), but higher stroke rate
      than girls (in opposition to what is described for adults). In addition, when
      considering the total sample, a higher relationship was observed between velocity
      and stroke length (than with stroke rate), indicating that improving stroke
      length is a fundamental skill to develop in these ages. Furthermore, only catch
      up coordination mode was adopted (being evident a lag time between propulsion of
      the arms), and the catch and the pull phases presented the highest and smallest
      durations, respectively.

PMID- 22971558
TI  - Locomotive and non-locomotive activity as determined by triaxial accelerometry
      and physical fitness in Japanese preschool children.
AB  - This study examined the potential relationship between participation in physical
      activity (PA) assessed by triaxial accelerometry and physical fitness testing,
      including health-related and skill-related parameters of fitness, in 136 Japanese
      preschoolers (65 girls and 71 boys, 5.5 +/- 0.6 years).  In partial correlation
      analyses, grip strength and 20m shuttle run test were positively correlated with
      time spent in physical activity ratio (PAR) >= 4. Better scores on standing long
      jump distance and jump over and crawl under tests were associated with lower
      sedentary time and greater moderate-to-vigorous PA time and PAR >= 4 time, and
      increased physical activity level. Moreover, 25m run speed was positively
      correlated with time spent in PAR >= 4 and locomotive activity. These findings
      suggest that development of both health-related (muscle strength and aerobic
      fitness) and skill-related fitness (power, agility and speed) may make engagement
      in PA easier for preschool children, although further research on the cause
      effect relationship is needed.

PMID- 22971559
TI  - Effects of locomotor skill program on minority preschoolers' physical activity
      levels.
AB  - This pilot study examined the effects of a teacher-taught, locomotor skill (LMS)
      based physical activity (PA) program on the LMS and PA levels of minority
      preschooler-aged children. Eight low-socioeconomic status preschool classrooms
      were randomized into LMS-PA (LMS-oriented lesson plans) or control group
      (supervised free playtime). Interventions were delivered for 30 min/day, five
      days/week for six months. Changes in PA (accelerometer) and LMS variables were
      assessed with MANCOVA. LMS-PA group exhibited a significant reduction in during
      preschool (F (1,16) = 6.34, p = .02, d = 0.02) and total daily (F (1,16) = 9.78,
      p = .01, d = 0.30) percent time spent in sedentary activity. LMS-PA group also
      exhibited significant improvement in leaping skills, F (1, 51) = 7.18, p = .01, d
      = 0.80). No other, significant changes were observed. The implementation of a
      teacher-taught, LMS-based PA program could potentially improve LMS and reduce
      sedentary time of minority preschoolers.

PMID- 22971560
TI  - Comparison of epoch and uniaxial versus triaxial accelerometers in the
      measurement of physical activity in preschool children: a validation study.
AB  - The objectives of this study were to explore whether triaxial is more accurate
      than uniaxial accelerometry and whether shorter sampling periods (epochs) are
      more accurate than longer epochs. Physical activity data from uniaxial and
      triaxial (RT3) devices were collected in 1-s epochs from 31 preschool children
      (15 males, 16 females, 4.4 +/- 0.8 yrs) who were videoed while they engaged in 1
      hr of free-play. Video data were coded using the Children's Activity Rating Scale
      (CARS). A significant difference (p < .001) in the number of minutes classified
      as moderate to vigorous physical activity (MVPA) was found between the RT3 and
      the CARS (p < .002) using the cut point of relaxed walk. No significant
      difference was found between the GT1M and the CARS or between the RT3 and the
      CARS using the cut point for light jog. Shorter epochs resulted in significantly
      greater overestimation of MVPA, with the bias increasing from 0.7 mins at 15-s to
      3.2 mins at 60-s epochs for the GT1M and 0 mins to 1.7 mins for the RT3. Results
      suggest that there was no advantage of a triaxial accelerometer over a uniaxial
      model. Shorter epochs result in significantly higher number of minutes of MVPA
      with smaller bias relative to direct observation.

PMID- 22971561
TI  - Adipocytokine levels in children: effects of fatness and training.
AB  - To investigate the effects of obesity and exercise training on plasma
      adipocytokines a sample of 42 children (lean = 24, %BF = 17.8 +/- 7.5%; obese =
      18; %BF = 29.1 +/- 9.3%; mean age = 12.4 +/- 1.9 yrs), were divided into 4 age
      matched for activity groups: lean inactive (n = 11), obese inactive (n = 9), lean
      active (n = 13) and obese active (n = 9). Active children participated in
      swimming training (>=1 year, >=3 times/week, >=1 h per session, covering a
      distance of 10,000-12,000 m per week).Obese individuals demonstrated greater
      visfatin levels (3.3 +/- 1.3 ng/ml) than their lean counterparts (2.6 +/- 1.1
      ng/ml; p = .06) whereas adiponectin was significantly lower in obese children
      (3.8 +/- 1.9) than their lean counterparts (5.9 +/- 2.7; p L .05). Insulin and
      HOMA values were significantly greater in obese compared with lean children (p L
      .05). Within obese individuals, active individuals had significantly lower
      visfatin levels (2.8 +/- 1.2 ng/ml) compared with their inactive counterparts
      (3.8 +/- 1.2 ng/ml; p L .05). Resistin levels were comparable between groups (p >
      .05). Childhood obesity elevates visfatin and lowers adiponectin levels whereas
      exercise training could reduce visfatin levels in obese children.

PMID- 22971562
TI  - The effect of physical training in children with asthma on pulmonary function,
      aerobic capacity and health-related quality of life: a systematic review of
      randomized control trials.
AB  - OBJECTIVE: Asthma is a leading cause of chronic illness in children, impacting
      heavily on their daily life and participation in physical activity. The purpose
      of this systematic review was to investigate the evidence for the use of physical
      therapy to improve pulmonary function and aerobic capacity in children with
      asthma. Furthermore, the review aims to update previous literature on the effect
      of exercise on health related quality of life. METHODS: A search was conducted
      for randomized control trials (RCTs) using the electronic databases Medline,
      Embase, SPORTDiscus, AMED, CINAHL, and The Cochrane Central Register of
      Controlled Trials. Studies were included if the participants were asthmatic
      children aged 6-18 years participating in any mode of physical exercise. Studies
      were reviewed for study quality, participant details, exercise intervention
      details, and intervention outcomes. RESULTS: A total of 16 studies and 516
      subjects met inclusion criteria for review. Severity of asthma ranged from mild
      to severe. No improvement in pulmonary function was observed. Physical training
      led to an increase in aerobic capacity as measured by VO(2max) (mL/kg/min).
      CONCLUSIONS: Findings suggest that physical training does not improve pulmonary
      function in children with asthma, but does increase aerobic capacity. The small
      number of studies investigating quality of life suggests that physical training
      does improve health related quality of life; however further well designed
      randomized control trials are needed to verify these findings.

PMID- 22971563
TI  - Surveillance for an outbreak of Encephalitozoon cuniculi infection in rabbits
      housed at a zoo and biosecurity countermeasures.
AB  - An outbreak of encephalitozoonosis occurred in a rabbit colony at a zoo in Japan.
      Throughout the two years after the onset, all 42 rabbits were investigated
      clinically, pathologically and serologically for prevention and control of the
      disease. Eleven rabbits (11/42, 26.2%) showed clinical symptoms. Of 38 rabbits
      examined to detect specific antibodies against Encephalitozoon cuniculi, 71.1%
      (n=27) were found seropositive; 20 out of 30 clinically healthy rabbits (except
      for 8 clinical cases) were seropositive. The infection rate was 76.2% (32/42),
      including 5 pathologically diagnosed cases. The results of serological survey
      revealed that asymptomatic infection was widespread, even among clinically
      healthy rabbits. However, encephalitozoonosis was not found by pathological
      examination in any other species of animals kept in the same area within the zoo.
      Isolation and elimination of the rabbits with suspected infection based on the
      results of serological examination were carried out immediately; however,
      encephalitozoonosis continued to occur sporadically. Therefore, all the remaining
      rabbits were finally slaughtered. Then, the facility was closed, and all the
      equipment was disinfected. After a two-month interval, founder rabbits were
      introduced from encephalitozoonosis-free rabbitries for new colony formation.
      Since then, encephalitozoonosis has not been seen in any animals at the zoo. In
      this study, biosecurity countermeasures including staff education,
      epidemiological surveillance and application of an "all-out and all-in" system
      for rabbit colony establishment based on serological examination were
      successfully accomplished with regard to animal hygiene and public health for the
      eradication of E. cuniculi.

PMID- 22971565
TI  - Development and validation of a simple and rapid liquid chromatography method for
      the determination of genistein in skin permeation studies.
AB  - Genistein (GEN) has potential advantages for topical skin delivery, but no
      literature data are available for its quantitation in different skin layers, such
      as the stratum corneum (SC). Therefore, a simple, rapid, selective and sensitive
      bioanalytical method was developed and validated for GEN quantitation in porcine
      skin samples following in vitro permeation studies. GEN was assayed by HPLC with
      UV-Vis detection (270 nm) using 0.5% acetic acid in water-n-propanol-acetonitrile
      (50 : 2 : 48, v/v/v) as mobile phase (flow-rate of 1.0 mL/min). Specificity was
      demonstrated since endogenous skin components did not interfere with GEN peak.
      Standard analytical curve was linear over the concentration range (0.1-60 ug/mL)
      and the lower limit of quantitation was determined for different skin layers (100
      ng/mL). GEN recovery from skin layers ranged from 95.57 to 97.57%. Permeation
      studies were carried out using an automated vertical diffusion cell apparatus. No
      fluctuation on the amount of GEN retained in the SC was observed over time, but
      increasing amounts of the drug were found in deeper layers of the skin. The
      method was reliable and reproducible for the quantitation GEN in skin samples
      enabling the determination of the cutaneous penetration profile of this drug in
      permeation experiments.

PMID- 22971564
TI  - Registration-based segmentation of murine 4D cardiac micro-CT data using
      symmetric normalization.
AB  - Micro-CT can play an important role in preclinical studies of cardiovascular
      disease because of its high spatial and temporal resolution. Quantitative
      analysis of 4D cardiac images requires segmentation of the cardiac chambers at
      each time point, an extremely time consuming process if done manually. To improve
      throughput this study proposes a pipeline for registration-based segmentation and
      functional analysis of 4D cardiac micro-CT data in the mouse. Following
      optimization and validation using simulations, the pipeline was applied to in
      vivo cardiac micro-CT data corresponding to ten cardiac phases acquired in
      C57BL/6 mice (n = 5). After edge-preserving smoothing with a novel adaptation of
      4D bilateral filtration, one phase within each cardiac sequence was manually
      segmented. Deformable registration was used to propagate these labels to all
      other cardiac phases for segmentation. The volumes of each cardiac chamber were
      calculated and used to derive stroke volume, ejection fraction, cardiac output,
      and cardiac index. Dice coefficients and volume accuracies were used to compare
      manual segmentations of two additional phases with their corresponding propagated
      labels. Both measures were, on average, >0.90 for the left ventricle and >0.80
      for the myocardium, the right ventricle, and the right atrium, consistent with
      trends in inter- and intra-segmenter variability. Segmentation of the left atrium
      was less reliable. On average, the functional metrics of interest were
      underestimated by 6.76% or more due to systematic label propagation errors around
      atrioventricular valves; however, execution of the pipeline was 80% faster than
      performing analogous manual segmentation of each phase.

PMID- 22971566
TI  - Immunology and Cell Biology Publication of the Year Awards 2011.

PMID- 22971569
TI  - Combined expression of antimicrobial genes (Bbchit1 and LJAMP2) in transgenic
      poplar enhances resistance to fungal pathogens.
AB  - Populus species are susceptible to infection by microbial pathogens that severely
      affect their growth and substantially decrease their economic value. In this
      study, two pathogenesis-related protein genes consisting of Beauveria bassiana
      chitinase (Bbchit1) and motherwort lipid-transfer protein (LJAMP2) were
      introduced into Chinese white poplar (Populus tomentosa Carr.) via Agrobacterium
      mediated transformation using the hygromycin (hyg) and neomycin
      phosphotransferase (NPTII) genes as selectable markers, respectively. Polymerase
      chain reaction analysis confirmed the stable integration of transgenes in the
      genome of transgenic plants. In vitro assays showed that inhibitory activity
      against the fungal pathogen Alternaria alternata (Fr.) Keissler was evident from
      the crude leaf extracts from transgenic plants. Importantly, the double
      transgenic plants exhibited significantly higher resistance to the pathogen than
      either of the single-gene transformants and wild-type plants when inoculated with
      A. alternata. The level of disease reduction in double-transgenic lines was
      between 82 and 95%, whereas that of single-gene transformants carrying either
      LJAMP2 or Bbchit1 was between 65 and 89%. These results indicated that the
      combined expression of the LJAMP2 and Bbchit-1 genes could significantly enhance
      resistance to necrotrophic fungal pathogens in poplar.

PMID- 22971570
TI  - Serum testosterone quantitation by liquid chromatography-tandem mass
      spectrometry: interference from blood collection tubes.
AB  - OBJECTIVES: During the development of a testosterone assay by LC-MS/MS, we
      encountered significant assay interference introduced by blood collection tubes.
      We examined a number of commonly used blood collection tubes for the presence of
      interference and its impact on testosterone quantitation. DESIGN AND METHODS: A
      number of commonly used blood collection tubes were examined by incubation of
      zero, low and high testosterone concentration samples with them over time,
      followed by sample preparation using liquid-liquid extraction and analysis by LC
      MS/MS. Source of interference was identified by separately incubating blood
      collection tube coating, stopper and separator gel in clean glass tubes
      containing zero calibrator. RESULTS: Significant interference was found in some
      blood collection tubes, with the separator gel identified as the main source. The
      magnitude of the interference increases over time and mainly affected one of the
      two testosterone mass transitions used in the quantitation, making it readily
      detected by the discrepant results obtained by each of the two testosterone mass
      transitions. We were unable to eliminate the interference by adjustment of the
      sample preparation procedure, and by changing LC or MS parameters. Accurate
      quantitation of testosterone is possible when the problematic tubes are avoided,
      and blood collection tubes free of interference are used instead. CONCLUSIONS:
      Significant LC-MS/MS testosterone assay interference that originated from certain
      type of blood collection tubes hampered testosterone analysis. Examination of
      blood collection tube and any other laboratory test tubes for interference should
      therefore be an integral part of the development and validation of any LC-MS/MS
      assay used in a clinical diagnostic laboratory.

PMID- 22971571
TI  - Optical microplates for high-throughput screening of photosynthesis in lipid
      producing algae.
AB  - It is well known that biological systems respond to chemical signals as well as
      physical stimuli. The workhorses of high throughput screening, microplates and
      pipetting robots, are well suited for screening chemical stimuli; however, there
      are fewer options for screening physical stimuli, particularly those which
      involve temporal patterns. This paper presents an optical microplate for photonic
      high-throughput screening. The system provides addressable intensity and temporal
      control of LED light emission in each well, and operates on standard black-wall
      clear-bottom 96-well microplates, which prevent light spillover. Light intensity
      can be controlled to 7-bit resolution (128 levels), with a maximum intensity of
      120 mE cm(-2). The temporal resolution, useful for studying dynamics of light
      driven bioprocesses, can be as low as 10 MUs. The microplate is used for high
      throughput studies of light-dependent growth rates and photosynthetic efficiency
      in the model organism Dunaliella tertiolecta, a lipid-producing algae of interest
      in 2(nd) generation biofuels. By conducting 96 experiments in parallel,
      photoirradiance studies, which would require 2 years using conventional tools,
      can be completed in <2 weeks. In a 12 day culture, algal growth rates increase
      with total photon flux, as expected. Interestingly, the lipid production
      efficiency, defined as lipid production per unit photon flux per capita,
      increases nearly 5 fold at low light intensity (constant light) and at low duty
      cycle (pulsed light). High throughput protocols enabled by this system are
      conducive to systematic studies and discovery in the fields of photobiology and
      photochemistry.

PMID- 22971572
TI  - Suicide or accident? A psychological autopsy study of suicide in youths under the
      age of 16 compared to deaths labeled as accidents.
AB  - OBJECTIVE: In the present paper, we describe suicide in youths under 16 years of
      age and compare their risk factors for suicide to those of older adolescents as
      described in the literature. Furthermore, we evaluate the possible mislabeling of
      suicides as accidents, and vice versa. METHOD: We used the data from a nationwide
      psychological autopsy of youths 15 years and younger who had committed suicide or
      died in accidents in Norway from 1993 to 2004 (n = 84). We additionally
      constructed a suicide index to distinguish between the two causes of death.
      RESULTS: The young suicide victims presented, with little gender difference,
      fewer obvious risk factors and less suicide intent than commonly described for
      older adolescents. The suicide index distinguished quite well between suicides
      and accidents, with few cases indicating a possible mislabeling, although some
      suicide cases could have been labeled as uncertain. CONCLUSION: In line with
      previous research, suicides in 11-15-year-olds have many similarities to suicides
      in older adolescents in terms of external circumstances, but they present less
      apparent warning signs. In our total sample of 84 deaths, there were few
      indications of incorrect labeling.

PMID- 22971573
TI  - Anticancer action of garcinol in vitro and in vivo is in part mediated through
      inhibition of STAT-3 signaling.
AB  - Garcinol, obtained from Garcinia indica, has exhibited some promising anticancer
      activity. In particular, our earlier work has demonstrated its ability to inhibit
      cell proliferation and induction of apoptosis in multiple cancer cell lines
      representative of breast, prostate, as well as pancreatic cancers. However, its
      exact mechanism of action remains largely unclear. Here we show that garcinol
      also targets signal transducer and activator of transcription-3 (STAT-3)
      signaling pathway. STAT-3 is frequently found to be activated in many cancer
      types and this is the first report on such action of garcinol leading to its
      anticancer effects. Garcinol inhibited total, as well as phosphorylated, STAT-3
      in breast, prostate and pancreatic cancer cell lines and was also found to
      inhibit cell invasion of all the cancer cell lines tested. STAT-3 phosphorylation
      was inhibited by garcinol in a dose-dependent manner. We also observed an
      inhibitory effect of garcinol on IL-6-induced STAT-3 phosphorylation and
      production of urokinase-type plasminogen activator, vascular endothelial growth
      factor and matrix metalloproteinase-9, which might explain the reduced invasion
      and aggressiveness of cells treated with garcinol. The results were further
      verified in vivo using MDA-MB-231 breast cancer mouse xenograft model where
      administration of garcinol significantly inhibited tumor growth, and western blot
      analysis of remnant tumor lysates showed reduced STAT-3 expression and
      activation. These results suggest that garcinol may have translational potential
      as chemopreventive or therapeutic agent against multiple cancers and inhibition
      of STAT-3 signaling pathway is one of the mechanisms by which garcinol exerts its
      anticancer effects.

PMID- 22971574
TI  - Genetic polymorphism at miR-181a binding site contributes to gastric cancer
      susceptibility.
AB  - Recent evidences show that genetic polymorphisms falling in miRNA binding sites
      can alter the strength of miRNA binding and disturb miRNA-mediated
      posttranscriptional regulation. Our study aimed to investigate the role of single
      nucleotide polymorphisms (SNPs) in putative miRNA binding sites in gastric cancer
      (GC). Based on microarray and quantitative reverse transcription PCR analyses, we
      found that miR-181a was significantly upregulated in GC tissues. Bioinformatics
      survey was used to explore SNPs within miR-181a binding sites. Three SNPs were
      genotyped in a case-control study (500 cases and 502 controls). The T allele
      genotypes (rs12537CT and TT) of MTMR3 were found associated with significantly
      increased GC risk [adjusted odds ratio 1.72, 95% confidence interval (CI) 1.36
      2.16, P = 3.99*10(-5)] and poor overall survival [hazard ratio (HR) 1.38, 95% CI
      1.03-1.83, P = 0.029], although they were not an independent prognostic factor in
      multivariate Cox regression analysis (HR 1.28, 95% CI 0.95-1.72, P = 0.11). We
      further demonstrated that the rs12537CT genotype carriers had lower MTMR3 mRNA
      expression levels than CC genotype carriers in GC tissues (P = 0.013), whereas no
      significant difference in miR-181a expression levels was found (P = 0.135).
      Luciferase assay revealed that miR-181a directly targeted MTMR3, and its
      suppressive effect was enhanced when the rs12537C allele was substituted by T
      variant, although the difference was not significant (P = 0.055). Our study
      suggested that rs12537 is associated with susceptibility and prognosis of GC in
      southern Han Chinese, and miR-181a and its target gene MTMR3 play important roles
      in GC.

PMID- 22971575
TI  - Focal adhesion kinase is required for beta-catenin-induced mobilization of
      epidermal stem cells.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates
      signals downstream of integrin and growth factor activation. Previously, we have
      shown that skin-specific loss of fak prevents chemically induced skin
      carcinogenesis in mice following phorbol ester treatment. In this study, we show
      that skin-specific deletion of fak prevents mobilization of stem cells within the
      bulge region of the hair follicle, which are the precursors of papillomas
      following phorbol ester treatment. We also show that phorbol ester treatment
      results in activation of-catenin within the skin and that FAK is required for
      beta-catenin-induced stem cell mobilization. In addition, inhibition of Src
      kinase activity, a major binding partner of FAK also prevents stem cell
      mobilization. We show that FAK is required for the nuclear localization of beta
      catenin in the skin following phorbol ester treatment and the transcriptional
      activation of the beta-catenin target gene c-Myc. This provides the first
      evidence of cross-talk between integrin and Wnt signalling pathways in the
      control of epidermal stem cells and the early events associated with skin
      carcinogenesis.

PMID- 22971576
TI  - Retinoic acid induced 16 enhances tumorigenesis and serves as a novel tumor
      marker for hepatocellular carcinoma.
AB  - Our previous work identified downregulated miR-483-5p in hepatocellular carcinoma
      (HCC). This study aims to identify the target of miR-483-5p, evaluate the
      potential value of this target as a tumor marker for HCC and explore the role of
      this target in HCC tumorigenesis. Upregulated retinoic acid induced 16 (RAI16)
      (17/18 cases) was negatively correlated with downregulated miR-483-5p (14/18
      cases) in HCC tissues. The dual-luciferase reporter assay showed that RAI16 is a
      target of miR-483-5p. Immunohistochemistry analysis showed RAI16 was moderate or
      strong staining in tumor tissues but negative or weak staining in adjacent non
      tumor tissues. The sensitivity and specificity of RAI16 for HCC diagnosis were
      70.6 and 93.6%, respectively, and increased to 80.9 and 92.0% when combined with
      glypican-3. Finally, overexpression or knockdown of RAI16 increased or decreased
      cell viability and colony formation in HCC cell lines and enhanced or inhibited
      tumor cell growth in xenograft nude mice. Mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) and transforming growth factor
      beta pathways were mostly affected by RAI16. RAI16 could activate the
      phosphorylation of ERK1/2 and SMAD2/3. In conclusion, RAI16 may serve as a useful
      therapeutic agent for HCC gene therapy and tumor marker for HCC diagnosis.

PMID- 22971577
TI  - Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas.
AB  - Members of the metallothionein (MT) family are short, cysteine-rich proteins
      involved in metal metabolism and detoxification, suggesting that MT proteins
      protect cells from damage caused by electrophilic carcinogens and thereby
      constitute a critical surveillance system against carcinogenesis. However, the
      roles of MT proteins in human hepatocellular carcinoma (HCC) are not fully
      understood. We identified a member of the MT family, termed MT1M. MT1M is
      expressed in various normal tissues with the highest level in the liver. MT1M
      expression can be induced by heavy metals and protect Escherichia coli from heavy
      metal toxicity. However, MT1M expression markedly decreased in human HCC
      specimens. A methylation profiling analysis indicated that the MT1M promoter is
      methylated in the majority of HCC tumors examined. Moreover, restored expression
      of MT1M in the HCC cell line Hep3B, which lacks endogenous MT1M expression,
      suppressed cell growth in vitro and in vivo and augmented apoptosis induced by
      tumor necrosis factor alpha. Furthermore, stable expression of MT1M in Hep3B
      cells blocked tumor necrosis factor alpha-induced degradation of IkappaBalpha and
      transactivation of NF-kappaB. We conclude that MT1M is a novel member of the MT
      family. Frequent downregulation of MT1M in human HCC may contribute to liver
      tumorigenesis by increasing cellular NF-kappaB activity.

PMID- 22971579
TI  - Systematic study of the physicochemical properties of a homologous series of
      aminobisphosphonates.
AB  - Aminobisphosphonates, e.g., alendronate and neridronate, are a well known class
      of molecules used as drugs for various bone diseases. Although these molecules
      have been available for decades, a detailed understanding of their most important
      physicochemical properties under comparable conditions is lacking. In this study,
      ten aminobisphosphonates, H(2)N(CH2)(n)C(OH)[P(O)(OH)(2)](2) in which n = 2-5, 7
      11 and 15 have been synthesized. Their aqueous solubility as a function of
      temperature and pH, pK(a-) values, thermal stability, IR absorptions, and NMR
      spectral data for both liquid (1)H, (13)C, (31)P-NMR and solid state(13)C, (15)N
      and (31)P-CPMAS NMR) were determined.

PMID- 22971580
TI  - A comparative study of the characteristics of cross-linked, oxidized and dual
      modified rice starches.
AB  - Rice starch was cross-linked with epichlorohydrin (0.3%, w/w, on a dry starch
      basis) and oxidized with sodium hypochlorite (2.5% w/w), respectively. Two dual
      modified rice starch samples (oxidized cross-linked rice starch and cross-linked
      oxidized rice starch) were obtained by the oxidation of cross-linked rice starch
      and the cross-linking of oxidized rice starch at the same level of reagents. The
      physicochemical properties of native rice starch, cross-linked rice starch and
      oxidized rice starch were also studied parallel with those of the two dual
      modified rice starch samples using rapid visco analysis (RVA), differential
      scanning calorimetry (DSC), dynamic rheometry and scanning electron microscopy
      (SEM). It was found that the levels of cross-linking and oxidation used in this
      study did not cause any significant changes in the morphology of rice starch
      granules. Cross-linked oxidized starch showed lower swelling power (SP) and
      solubility, and higher paste clarity in comparison with native starch. Cross
      linked oxidized rice starch also had the lowest tendency of retrogradation and
      highest ability to resistant to shear compared with native, cross-linked,
      oxidized and oxidized cross-linked rice starches. These results suggest that the
      undesirable properties in native, cross-linked and oxidized rice starch samples
      could be overcome through dual-modification.

PMID- 22971578
TI  - Production and characterization of human anti-V3 monoclonal antibodies from the
      cells of HIV-1 infected Indian donors.
AB  - BACKGROUND: Analysis of human monoclonal antibodies (mAbs) developed from HIV-1
      infected donors have enormously contributed to the identification of
      neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third
      variable region (V3) is a crucial target on gp120, primarily due to its
      involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes
      recognized by broadly neutralizing antibodies. METHODS: Thirty-three HIV-1
      seropositive drug naive patients (18 males and 15 females) within the age range
      of 20-57 years (median = 33 years) were recruited in this study for mAb
      production. The mAbs were selected from EBV transformed cultures with
      conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion
      protein. We tested the mAbs for their binding with HIV-1 derived proteins and
      peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays.
      RESULTS: We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of
      different individuals. The ELISA binding revealed a subtype-C and subtype-A
      specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity
      also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides
      showed exclusive binding to V3 crown. The antibodies displayed high and low
      neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively.
      Overall, we observed a resistance of the tier 2 viruses to neutralization by the
      anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies
      on two representative native viruses (Du156.12 and JRFL), suggesting that the
      affinity of mAb might equally be crucial for neutralization, as the epitope
      recognition. CONCLUSIONS: Our study suggests that the anti-V3 antibodies derived
      from subtype-C infected Indian patients display neutralization potential against
      tier 1 viruses while such activity may be limited against more resistant tier 2
      viruses. Defining the fine epitope specificities of these mAbs and further
      experimental manipulations will be helpful in identification of epitopes, unique
      to clade C or shared with non-clade C viruses, in context of V3 region.

PMID- 22971582
TI  - Steady impact factor growth for MDPI open access journals.
AB  - For the past three years MDPI has announced the newly released impact factors for
      its Open Access journals by the means of an annual editorial [1-3]. In 2012 we
      are-once again-pleased to report that the growth of the impact factors of MDPI's
      Open Access journals continues. This year's edition of the Journal Citation
      Reports (JCR), which is published annually by Thomson Reuters, includes 10
      journals published by MDPI, including three that have received their first
      official Impact Factors- International Journal of Environmental Research and
      Public Health (IJERPH), Materials Nutrients. Table 1 reports the latest Impact
      Factors for 2011. Figure 1 graphically depicts the evolution of the Impact
      Factors for four MDPI open access journals that have received Impact Factors in
      the past. Table 2 reports the ranking of the MDPI journals within the subject
      categories of the Science Citation Index Expanded.

PMID- 22971581
TI  - Applied biological and physicochemical activity of isoquinoline alkaloids:
      oxoisoaporphine and boldine.
AB  - The aim of this study was to determine the electronic influence of substituent
      groups and annelated rings such as oxazole-oxazinone on the physicochemical and
      photoprotection, antioxidant capacity, toxicity and singlet oxygen
      photosensitization biological properties of isoquinoline alkaloid frameworks.
      Thus, oxoisoaporphine derivatives 1-5 and 3-azaoxoisoaporphine (6), some of them
      with phenolic structures, did not present any antioxidant capacity, possibly
      either by formation of keto-enol tautomerism species or the formation of unstable
      free radicals. Due to the singlet oxygen quantum yields (FD) near to unity, and
      greater photostability than phenalenone, oxoisoaporphines 4-6 may be considered
      as photosensitizers for singlet oxygen production and can be used as new
      universal study tools. The biological application as antibacterial agents is an
      important and possible tool in the study of compounds with low cytotoxicity and
      high reactivity in antineoplastic chemotherapy. On the other hand, when boldine
      and its annelated derivatives B1-4 are irradiated, a photoprotector effect is
      observed (SPF = 2.35), even after 30 minutes of irradiation. They also act as
      photoprotectors in cell fibroblast cultures. No hemolysis was detected for
      boldine hydrochloride and its salts without irradiation. In solutions irradiated
      before incubation (at concentrations over 200 ppm) photoproducts were toxic to
      the nauplii of Artemia salina.

PMID- 22971583
TI  - A structural study of epoxidized natural rubber (ENR-50) and its cyclic
      dithiocarbonate derivative using NMR spectroscopy techniques.
AB  - A structural study of epoxidized natural rubber (ENR-50) and its cyclic
      dithiocarbonate derivative was carried out using NMR spectroscopy techniques. The
      overlapping (1)H-NMR signals of ENR-50 at delta 1.56, 1.68-1.70, 2.06, 2.15-2.17
      ppm were successfully assigned. In this work, the <(13)C-NMR chemical shift
      assignments of ENR-50 were consistent to the previously reported work. A cyclic
      dithiocarbonate derivative of ENR-50 was synthesized from the reaction of
      purified ENR-50 with carbon disulfide (CS(2)), in the presence of 4
      dimethylaminopyridine (DMAP) as catalyst at reflux temperature. The cyclic
      dithiocarbonate formation involved the epoxide ring opening of the ENR-50. This
      was followed by insertion of the C-S moiety of CS(2) at the oxygen attached to
      the quaternary carbon and methine carbon of epoxidized isoprene unit,
      respectively. The bands due to the C=S and C-O were clearly observed in the FTIR
      spectrum while the (1)H-NMR spectrum of the derivative revealed the peak
      attributed to the methylene protons had split. The (13)C-NMR spectrum of the
      derivative further indicates two new carbon peaks arising from the >C=S and
      quaternary carbon of cyclic dithiocarbonate. All other (1)H- and (13)C-NMR
      chemical shifts of the derivative remain unchanged with respect to the ENR-50.

PMID- 22971584
TI  - Inhibition of cytochrome P450 3A in rat liver by the Diorganotin (IV) compound di
      n-Butyl-di-(4-chlorobenzo-hydroxamato)tin (IV) and Its Probable Mechanism.
AB  - The specific aims of this study were to evaluate the inhibition effect on CYP3A
      of di-n-butyl-di-(4-chlorobenzohydroxamato)tin (IV) (DBDCT), a tin-based complex
      with high antitumor activity, and the probable mechanism(s) of this action. Adult
      male SD rats were treated separately with natural saline (NS), lipopolysaccharide
      (LPS, 5 mg/kg), DBDCT (1.25, 2.5 and 5.0 mg/kg) intraperitoneally for 2 days
      after induction of CYP3A with dexamethasone (DEX, 100 mg/kg) for 4 days. Western
      blot analysis and fluorescent quantitation PCR (FQ-PCR) were conducted to
      determine the changes in expression of CYP3A, PXR, CAR and RXR. The biological
      accumulation of DBDCT and total Sn were determined by high-performance liquid
      chromatography (HPLC) and atomic fluorescence spectrometry (AFS). CYP450 content
      and CYP3A activities were significantly inhibited (p < 0.05) in DBDCT-treated
      rats compared with the control group, as was the expression of CYP3A (p < 0.05)
      at both protein and mRNA levels. In DBDCT-treated groups, the expression of PXR
      protein and mRNA increased, while the expression of CAR decreased. The biological
      accumulation of DBDCT and Sn in rat livers treated with DBDCT was high. The
      accumulation of DBDCT and Sn due to the inhibition of CYP3A may be involved in
      the mechanism of toxicity of DBDCT in rat liver.

PMID- 22971585
TI  - Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and
      purine moieties: synthesis and evaluation of their cytostatic activity.
AB  - We report here on the synthesis and in vitro anti-tumor effects of a series of
      novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and
      purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside
      analogues 14-18. Structures of novel compounds 3-18 were deduced from their (1)H-
      and (13)C-NMR and corresponding mass spectra. Results of anti-proliferative
      assays performed on a panel of selected human tumor cell lines revealed that
      compound 6 had moderate cytostatic activity against the HeLa cell line (IC(50) =
      35 uM), whereas compound 10 showed moderate activity against the HeLa (IC(50) =
      33 uM), HepG2 (IC(50) = 25 uM) and SW620 (IC(50) = 35 uM) cell lines. These
      compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.

PMID- 22971586
TI  - Etomidate is associated with mortality and adrenal insufficiency in sepsis: a
      meta-analysis*.
AB  - OBJECTIVE: To evaluate the effects of single-dose etomidate on the adrenal axis
      and mortality in patients with severe sepsis and septic shock. DESIGN: A
      systematic review of randomized controlled trials and observational studies with
      meta-analysis. SETTING: Literature search of EMBASE, Medline, Cochrane Database,
      and Evidence-Based Medical Reviews. SUBJECTS: Sepsis patients who received
      etomidate for rapid sequence intubation. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: We conducted a systematic review of randomized controlled trials
      and observational studies with meta-analysis assessing the effects of etomidate
      on adrenal insufficiency and all-cause mortality published between January 1950
      and February 2012. We only examined studies including septic patients. All-cause
      mortality served as our primary end point, whereas the prevalence of adrenal
      insufficiency was our secondary end point. Adrenal insufficiency was determined
      using a cosyntropin stimulation test in all studies. We used a random effects
      model for analysis; heterogeneity was assessed with the I statistic. Publication
      bias was evaluated with Begg's test. Five studies were identified that assessed
      mortality in those who received etomidate. A total of 865 subjects were included.
      Subjects who received etomidate were more likely to die (pooled relative risk
      1.20; 95% confidence interval 1.02-1.42; Q statistic, 4.20; I2 statistic, 4.9%).
      Seven studies addressed the development of adrenal suppression associated with
      the administration of etomidate; 1,303 subjects were included. Etomidate
      administration increased the likelihood of developing adrenal insufficiency
      (pooled relative risk 1.33; 95% confidence interval 1.22-1.46; Q statistic, 10.7;
      I2 statistic, 43.9%). CONCLUSIONS: Administration of etomidate for rapid sequence
      intubation is associated with higher rates of adrenal insufficiency and mortality
      in patients with sepsis.

PMID- 22971587
TI  - Coinfection with Staphylococcus aureus increases risk of severe coagulopathy in
      critically ill children with influenza A (H1N1) virus infection.
AB  - OBJECTIVES: H1N1 influenza with coinfections has been implicated to have high
      morbidity and mortality. We hypothesized that critically ill children with 2009
      H1N1 and coinfections are at a higher risk of developing disseminated
      intravascular coagulation. DESIGN: The chart review included demographics, length
      of-stay, severity of illness score (Pediatric Risk of Mortality III acute
      physiology score), clinical laboratories, and outcomes at hospital day 90 data.
      Patients were classified as having methicillin-sensitive or -resistant
      Staphylococcus aureus, other, or no coinfections. SETTING: Single-center
      pediatric intensive care unit. PATIENTS: Sixty-six consecutive patients with 2009
      H1N1 and influenza A infection. INTERVENTIONS: None. MAIN RESULTS: : There were
      12, 22, and 32 patients with methicillin-sensitive or -resistant Staphylococcus
      aureus, other, and no coinfections, respectively. Pediatric critical care unit
      length-of-stay was 11, 10, and 5.5 days (median), and survival at day 90 was 83%,
      96%, and 91% in patients with methicillin-sensitive or -resistant Staphylococcus
      aureus, other, and no coinfections. Patients with methicillin-sensitive or 
      resistant Staphylococcus aureus coinfections compared to patients with other, and
      no coinfections had higher Pediatric Risk of Mortality III acute physiology
      scores (14 [6-25] vs. 7 [2-10], p = .052 and 6 [2.5-10], p = .008; median
      [interquartile range]), higher D-dimer (16.1 [7.9-19.3] vs. 1.6 [1.1-4], p = .02
      and 2.3 [0.8-8.7] ug/mL, p = .05), longer prothrombin time (19.3 [15.4-25.9] vs.
      15.3 [14.8-17.1], p = .04 and 16.6 [14.7-20.4] secs, p < .39) at admission, and
      lower day-7 platelet counts (90K [26-161K] vs. 277K [98-314], p = .03 and 256K
      [152-339]/mm, p < .07). Patients with methicillin-sensitive or -resistant
      Staphylococcus aureus coinfections compared to patients without coinfections were
      more likely to be sicker with Pediatric Risk of Mortality III acute physiology
      score >10 vs. <10 (relative risk 2.4; 95% confidence interval 1.2-4.7; p = .035)
      and have overt disseminated intravascular coagulation (relative risk 4.4; 95%
      confidence interval 1.3-15.8, p = .025). CONCLUSIONS: During the 2009-2010 H1N1
      pandemic, pediatric patients with influenza A and methicillin-sensitive or 
      resistant Staphylococcus aureus coinfections were sicker and more likely to
      develop disseminated intravascular coagulation than patients with other or no
      coinfections.

PMID- 22971588
TI  - Interferon-gamma production by natural killer cells and cytomegalovirus in
      critically ill patients.
AB  - OBJECTIVE: The mechanisms involved in cytomegalovirus reactivation in critically
      ill patients who were previously immunocompetent are still unknown. The current
      study was designed to evaluate the possible role of natural killer cells in the
      reactivation of cytomegalovirus in these patients. DESIGN: Prospective
      observational. SETTING: : A medical intensive care unit of a university hospital.
      PATIENTS: Fifty-one subjects, including 15 patients who experienced
      cytomegalovirus reactivation (cases) during their intensive care unit stay and 15
      patients who matched intensive care unit controls, selected from a cohort of
      consecutive nonimmunocompromised intensive care unit patients, as well as healthy
      controls. INTERVENTIONS: Tests included weekly systematic immunomonitoring and
      routine screening for cytomegalovirus infection until discharge from the
      intensive care unit or death. The immunophenotype and functions of natural killer
      cells were performed by flow cytometry, and serum levels of pro- and anti
      inflammatory cytokines were determined by enzyme-linked immunosorbent assay.
      MEASUREMENTS AND MAIN RESULTS: The overall occurrence of cytomegalovirus
      reactivation in the cohort was 27%. No differences of natural killer cell
      effector functions were observed at admission between cases and controls.
      Instead, before cytomegalovirus reactivation, the ability of natural killer cells
      to secrete interferon-gamma was significantly reduced in cases as compared with
      controls upon stimulation with antibody-coated target cells (p = .029) and with
      K562 cell stimulation (p = .029). No phenotypic or quantitative differences were
      observed between cases and controls. Cases exhibited higher levels of interleukin
      10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus
      reactivation. CONCLUSIONS: Impaired natural killer cell function with reduced
      interferon-gamma secretion precedes the occurrence of cytomegalovirus
      reactivation among previously immunocompetent critically ill patients.

PMID- 22971590
TI  - Association between intensive care unit-acquired dysglycemia and in-hospital
      mortality.
AB  - OBJECTIVE: Our objective was to quantify the association between intensive care
      unit-acquired dysglycemia (hyperglycemia, hypoglycemia, and high variability) and
      in-hospital mortality. DESIGN: Retrospective, observational study. SETTING: eICU
      Research Institute participating hospitals with an active tele-ICU program
      between January 1, 2008, and September 30, 2010, representing 784,392 adult
      intensive care unit patients. PATIENTS: A total of 194,772 patients met inclusion
      criteria with an intensive care unit length of stay >48 hrs. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation IV
      standardized mortality ratios were calculated for dysglycemia present at
      admission and acquired in the intensive care unit. Intensive care unit-acquired
      dysglycemia was modeled using multivariable modified Poisson regression to
      account for confounding not incorporated in Acute Physiology and Chronic Health
      Evaluation. Dysglycemia severity was assessed by the relative risk of in-hospital
      mortality associated with the maximum, time-weighted average daily glucose;
      lowest glucose value throughout the intensive care unit stay; and quintiles of
      variability (coefficient of variation). The association of duration beyond
      thresholds of dysglycemia on mortality was also modeled. The adjusted relative
      risk (95% confidence interval) of mortality for the maximum intensive care unit
      average daily glucose was 1.13 (1.04-1.58), 1.43 (1.30-1.58), 1.63 (1.47-1.81),
      1.76 (1.55-1.99), and 1.89 (1.62-2.19) for 110-150 mg/dL, 151-180 mg/dL, 180-240
      mg/dL, 240-300 mg/dL, and >300 mg/dL, respectively, compared to patients whose
      highest average daily glucose was 80-110 mg/dL. The relative risk of mortality
      for the lowest glucose value was 1.67 (1.37-2.03), 1.53 (1.37-1.70), 1.12 (1.04
      1.21), and 1.06 (1.01-1.11) for <20 mg/dL, 20-40 mg/dL, 40-60 mg/dL, and 60-80
      mg/dL, respectively, compared to patients whose lowest value was 80-110 mg/dL.
      The relative risk of mortality increased with greater duration of hyperglycemia
      and with increased variability. The relative risk for the highest compared to
      lowest quintile of variability was 1.61 (1.47-1.78). The association of duration
      of hyperglycemia on mortality was more pronounced with more severe hyperglycemia.
      CONCLUSIONS: The risk of mortality progressively increased with severity and
      duration of deviation from euglycemia and with increased variability. These data
      suggest that severe intensive care unit-acquired hyperglycemia, hypoglycemia, and
      variability are associated with similar risks of mortality.

PMID- 22971589
TI  - Hyperoxia is associated with increased mortality in patients treated with mild
      therapeutic hypothermia after sudden cardiac arrest.
AB  - OBJECTIVE: To determine whether higher levels of PaO2 are associated with in
      hospital mortality and poor neurological status at hospital discharge in patients
      treated with mild therapeutic hypothermia after sudden cardiac arrest. DESIGN:
      Retrospective analysis of a prospective cohort. PATIENTS: A total of 170
      consecutive patients treated with therapeutic hypothermia in the cardiovascular
      care unit of an academic tertiary care hospital. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Of 170 patients, 77 (45.2%) survived to hospital
      discharge. Survivors had a significantly lower maximum PaO2 (198 mm Hg;
      interquartile range, 152.5-282) measured in the first 24 hrs following cardiac
      arrest compared to nonsurvivors (254 mm Hg; interquartile range, 172-363; p =
      .022). A multivariable analysis including age, time to return of spontaneous
      circulation, the presence of shock, bystander cardiopulmonary resuscitation, and
      initial rhythm revealed that higher levels of PaO2 were significantly associated
      with increased in-hospital mortality (odds ratio 1.439; 95% confidence interval
      1.028-2.015; p = .034) and poor neurological status at hospital discharge (odds
      ratio 1.485; 95% confidence interval 1.032-2.136; p = .033). CONCLUSIONS: Higher
      levels of the maximum measured PaO2 are associated with increased in-hospital
      mortality and poor neurological status on hospital discharge in patients treated
      with mild therapeutic hypothermia after sudden cardiac arrest.

PMID- 22971591
TI  - Analysis of structural and electronic properties of Pr2NiO4 through first
      principles calculations.
AB  - The structural and electronic properties of bulk Pr(2)NiO(4+delta) (delta = 0 and
      0.031) were analyzed using first-principles calculations based on the density
      functional theory (DFT) for application to electrode materials in solid-oxide
      fuel cells (SOFCs). Two structures of Pr(2)NiO(4) were analyzed: one in space
      group I4/mmm associated with the high temperature tetragonal (HTT) structure, and
      the other in Bmab with the low temperature orthorhombic (LTO) structure. The main
      difference between the two structures is the pronounced tilting of the nickelate
      octahedra found in the Bmab structure. Here, we will show that the difference in
      the electronic properties between the two structures, i.e. half-metallic for the
      I4/mmm structure and metallic for the Bmab structure, is attributed to the
      tilting of the nickelate octahedra. Furthermore, we found that the presence of
      interstitial O atoms at the Pr(2)O(2) bilayers is responsible for the tilting of
      the octahedra and thus is a dominant factor in the transition from the I4/mmm
      structure to the Bmab structure. These results would be of great significance to
      materials design related to the enhancement of O diffusivity in this material.

PMID- 22971592
TI  - Neuroprotective effect of sinapic acid in a mouse model of amyloid beta(1-42)
      protein-induced Alzheimer's disease.
AB  - Sinapic acid (SA) is a phenylpropanoid compound with anti-inflammatory and
      neuroprotective activities. The neuroprotective effects of SA in a mouse model of
      amyloid beta (Abeta)(1-42) protein-induced Alzheimer's disease (AD) were
      investigated. Mice received a bilateral injection of Abeta(1-42) protein into the
      hippocampus to verify the efficacy of SA. Mice were treated with SA (10mg/kg/day,
      p.o.) for 7days beginning immediately after Abeta(1-42) protein injection, and an
      acquisition trial of the passive avoidance task was conducted 1h after the last
      administration of SA. Retention trial was conducted 24h after the acquisition
      trial, and mice were sacrificed for immunohistochemistry immediately after the
      retention trial. SA rescued neuronal cell death in the hippocampal CA1 region and
      also attenuated the increase of iNOS expression, glial cell activations and
      nitrotyrosine expressions induced by Abeta(1-42) protein. SA significantly
      attenuated memory impairment in the passive avoidance task. These results suggest
      that SA ameliorated Abeta(1-42) protein-related pathology including neuronal cell
      death and cognitive dysfunction via its anti-oxidative and anti-inflammatory
      activities, and may be an efficacious treatment for AD.

PMID- 22971594
TI  - Inhibitory effects of hydroxysafflor yellow A on the formation of advanced
      glycation end products in vitro.
AB  - To investigate the inhibitory effects of hydroxysafflor yellow A (HSYA) on the
      protein glycation in vitro. Using bovine serum albumin (BSA)-glucose assay, BSA
      methylglyoxal (MGO) assay, and N-acetylglycyl-lysine methyl ester (G.K.) peptide
      ribose assay, inhibitory effects of HSYA were investigated. Advanced glycation
      end products (AGEs) production was assessed by AGEs-specific fluorescence and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In BSA
      glucose assay, HSYA concentration dependently decreased AGEs formation, with
      maximum inhibitory effects at 1 mM by 95%. Further more, HSYA also showed
      significant inhibitory effects on MGO-medicated protein modification and
      subsequent cross-linking of proteins. Finally, when co-incubated with G.K.
      peptide and ribose, HSYA exhibited its antiglycation effects, and the maximum
      inhibitory effects of HSYA at 1 mM were 84%. Overall, our present study provides
      the first evidence of the antiglycation effects of HSYA on AGEs formation in
      vitro.

PMID- 22971593
TI  - The cost-effectiveness of rapid HIV testing in substance abuse treatment: results
      of a randomized trial.
AB  - BACKGROUND: The President's National HIV/AIDS Strategy calls for coupling HIV
      screening and prevention services with substance abuse treatment programs. Fewer
      than half of US community-based substance abuse treatment programs make HIV
      testing available on-site or through referral. METHODS: We measured the cost
      effectiveness of three HIV testing strategies evaluated in a randomized trial
      conducted in 12 community-based substance abuse treatment programs in 2009: off
      site testing referral, on-site rapid testing with information only, on-site rapid
      testing with risk-reduction counseling. Data from the trial included patient
      demographics, prior testing history, test acceptance and receipt of results,
      undiagnosed HIV prevalence (0.4%) and program costs. The Cost-Effectiveness of
      Preventing AIDS Complications (CEPAC) computer simulation model was used to
      project life expectancy, lifetime costs, and quality-adjusted life years (QALYs)
      for HIV-infected individuals. Incremental cost-effectiveness ratios (2009 US
      $/QALY) were calculated after adding costs of testing HIV-uninfected individuals;
      costs and QALYs were discounted at 3% annually. RESULTS: Referral for off-site
      testing is less efficient (dominated) compared to offering on-site testing with
      information only. The cost-effectiveness ratio for on-site testing with
      information is $60,300/QALY in the base case, or $76,300/QALY with 0.1%
      undiagnosed HIV prevalence. HIV risk-reduction counseling costs $36 per person
      more without additional benefit. CONCLUSIONS: A strategy of on-site rapid HIV
      testing offer with information only in substance abuse treatment programs
      increases life expectancy at a cost-effectiveness ratio <$100,000/QALY.
      Policymakers and substance abuse treatment leaders should seek funding to
      implement on-site rapid HIV testing in substance abuse treatment programs for
      those not recently tested.

PMID- 22971595
TI  - Simultaneous detection of canine respiratory disease associated viruses by a
      multiplex reverse transcription-polymerase chain reaction assay.
AB  - A multiplex reverse transcription polymerase chain reaction (mRT-PCR) assay was
      developed for the simultaneous detection of canine distemper virus (CDV), canine
      respiratory coronavirus (CRCoV) and canine influenza virus (CIV). These viral
      pathogens are all causative agents of canine infectious respiratory disease
      (CIRD). The sensitivity and specificity of the mRT-PCR were determined by
      comparing it to a rapid antigen test (RAT) or immuno-chromatography test kit and
      reverse transcription-polymerase chain reaction (RT-PCR) in the detection of CDV,
      CRCoV and CIV antigens present in 100 clinical samples (nasal swabs and whole
      blood samples) from 50 dogs with respiratory disease symptoms. This study
      revealed that mRT-PCR had almost exactly the same performance or results were
      almost 100% in agreement with that of RT-PCR and RAT both in terms of the assay
      sensitivity and specificity which was more highly evident in detecting CIV, CDV
      and CRCoV antigens present in canine nasal swab samples. Therefore, this assay
      could be a better alternative for the definitive and simultaneous ante-mortem
      detection of the three viral pathogens that cause CIRD by using nasal swabs.

PMID- 22971602
TI  - Functional cooperation of SMCTs and URAT1 for renal reabsorption transport of
      urate.
AB  - Urate is mainly excreted into urine in humans. Serum urate level is regulated
      by a urate transport system located on the renal proximal tubule. Urate
      transporter 1 (URAT1) is located on the apical side of the renal proximal tubule
      and is responsible for the reabsorption of urate from the luminal side into
      tubular cells. At the same site, it has been hypothesized that sodium-coupled
      monocarboxylate transporters (SMCTs) are responsible for the transportation of
      monocarboxylates such as lactate and nicotinate, which are exchanged for urate
      transport via URAT1. Accordingly, SMCTs could enhance URAT1-mediated urate
      reabsorption by providing monocarboxylates for the exchange. The present study
      was carried out to clarify the hypothesized functional cooperative relationship
      between URAT1 and SMCTs in the reabsorptive transport of urate. By preloading
      nicotinate in SMCT1/URAT1-coexpressing Xenopus oocytes, URAT1-mediated urate
      transport was stimulated. Nicotinate was taken up by SMCT1 but not by URAT1. When
      removing sodium ions from the uptake medium, the stimulation effect was
      decreased. When adding SMCT1 inhibitors, the stimulation effect was also reduced.
      The results from this study indicate the cooperative relationship of URAT1 and
      SMCT1, and that SMCT1 is a potential target for the alteration of renal handling
      of urate indirectly.

PMID- 22971603
TI  - Editorial process in Japan.

PMID- 22971604
TI  - Operative repair of massive rotator cuff tears: Long-term results.
AB  - Sixty-one patients had operative repair of a massive rotator cuff tear and were
      followed an average of 7 years (range 3 to 13 years). The mean age of the
      patients was 62 years; there were 40 male and 21 female patients. All patients
      had significant pain, 31 patients had insidious onset of pain, and 30 patients
      recalled a traumatic event. Preoperatively, average active forward elevation was
      88 degrees , and average active external rotation was 27 degrees . Forty-nine
      (80%) patients had marked atrophy of the supraspinatus and infraspinatus muscles.
      All patients had subacromial decompression as well as mobilization and
      transposition of rotator cuff tendons with tendon repair to bone. Fifty-two (85%)
      patients had satisfactory results, with 32 (52%) rated excellent and 20 (33%)
      rated good. Nine (15%) patients had unsatisfactory results, with four (7%) rated
      fair and five (8%) rated poor. Ninety-two percent of patients had satisfactory
      pain relief. The mean gain in forward elevation was 76%, and in active external
      rotation it was 30 degrees . Adequate pain relief and the ability to raise the
      arm above the horizontal plane were achieved in 56 (92%) patients. Two patients
      tore their rotator cuff again after significant trauma.

PMID- 22971605
TI  - Scapular inclination and inferior stability of the shoulder.
AB  - Eleven fresh-frozen cadaver shoulders were studied to examine the influence of
      scapular inclination on inferior stability of the glenohumeral joint. All muscles
      except the rotator cuff were removed, and the capsule was vented. Inferior
      stability tests in the hanging position (sulcus test) and in 90 degrees 
      abduction (abduction inferior stability [ABIS] test) were simulated by the
      application of a 1.5 kg load with the scapula inclined at - 15 degrees , 0
      degrees , 15 degrees , and 30 degrees  in the sulcus test and at 15 degrees , 30
      degrees , 45 degrees , and 60 degrees  in the ABIS test. An electromagnetic
      tracking device was used to record the position of the humerus in relation to the
      glenoid. In the sulcus test all of the shoulders dislocated when the scapula was
      inclined at - 15 degrees . However, when the scapula was inclined at 30 degrees ,
      no shoulder dislocated before loading, and one shoulder dislocated after loading.
      As a result both the loaded and unloaded positions of the humeral head shifted
      significantly to the superior direction as the scapular inclination increased (p
      < 0.0001). In the ABIS test, however, the positions of the humeral head shifted
      interiorly with an increase in scapular inclination (p < 0.0001), although none
      of the shoulders dislocated in any of the inclination angles. We conclude that
      scapular inclination contributes significantly to inferior stability of the
      glenohumeral joint. Increased scapular inclination prevents inferior displacement
      of the humeral head, probably because of a bony cam effect that causes tightening
      of the superior capsule.

PMID- 22971606
TI  - Anterior shoulder stability: Contributions of rotator cuff forces and the
      capsular ligaments in a cadaver model.
AB  - The purpose of this study was to quantify in a biomechanical model the
      contributions to shoulder joint stability that are made by tensions in the four
      tendons of the rotator cuff and by static resistance of defined portions of the
      capsular ligaments. A materials testing machine was used to directly determine
      anterior joint laxity by measurement of the force required to produce a standard
      anterior subluxation. Shoulders were tested in external or neutral humeral
      rotation. Data were analyzed by multiway analysis of variance with regression
      analysis. This model simulated tensions in the rotator cuff musculature by
      applying static loads at the tendon insertion sites acting along the anatomic
      lines of action. A load in any of the cuff tendons resulted in a measurable and
      statistically significant contribution to anterior joint stability. The
      contributions between different tendons were not significantly different and did
      not depend on the humeral rotation (neutral or external). In neutral humeral
      rotation the superior and middle glenohumeral ligaments together function equally
      with the inferior glenohumeral ligament as primary stabilizers against anterior
      humeral translation. The posterior capsule is a secondary stabilizer. The
      external rotation of the abducted humerus increases anterior stability by more
      than doubling the stability contribution from the inferior glenohumeral ligament.
      The stability contribution from the posterior capsule is larger in external
      rotation than in neutral rotation but is still of secondary magnitude. In
      external rotation the stability contribution of the anterior capsule, including
      the superior glenohumeral ligament and the middle glenohumeral ligament, becomes
      insignificant. The model presented here simulates the combined effect of two
      major sources of shoulder stability. This versatile model permits the direct
      measurement of the contributions to anterior shoulder stability that are made by
      tensions in the rotator cuff tendons and by static resistance of defined capsular
      zones. The use of multiple regression analysis-a standard statistical technique
      but one relatively new to the orthopaedic literature-permits quantitative
      determination of the contribution of each independent variable to the dependent
      variable, shoulder stability.

PMID- 22971607
TI  - Focal cortical bone loss at the inferior aspect of the glenoid: A new
      radiographic sign of anterior shoulder instability.
AB  - This report describes the detection of localized cortical bone loss at the
      inferior glenoid with the use of anteroposterior radiographs of the shoulder.
      This bone loss was noticed in two of 100 patients who had recurrent anterior
      instability of traumatic origin. Double-contrast arthrography and the operative
      findings disclosed that this lesion coincided anatomically with the scapular
      insertion of the detached anterior capsule. A survey of 544 radiographs from
      patients who had various other shoulder disorders did not detect any similar bony
      changes. Thus this pattern of bone loss, although small and uncommon, appears to
      be a new radiographic sign of damage to the anterior capsular mechanism.

PMID- 22971608
TI  - Correction.

PMID- 22971609
TI  - Syringomyelia presenting as shoulder instability.
AB  - Three middle-aged women presented with shoulder instability as the first sign of
      syringomyelia. The patients' symptoms were unilateral in each case. Two patients
      had posterior shoulder instability, and one patient had anterior instability. Two
      patients had undergone surgery to stabilize the shoulder before referral to our
      center. In both cases the surgery had been unsuccessful. Review of two of the
      patients' plain radiographs after referral demonstrated radiographic changes
      highly suggestive of neuropathic arthropathy. The diagnosis of syringomyelia was
      confirmed by myelography, computed tomographic scanning, and magnetic resonance
      imaging. One patient had an associated Arnold-Chiari malformation that was
      treated by a syringosubarachnoid shunt. Each patient's shoulder disability,
      although significant, remained static throughout a follow-up period averaging 79
      months. Shoulder instability can be a presenting symptom and sign of
      syringomyelia. Patients over age 40 presenting with a glenohumeral dislocation
      may, in addition to having a high probability of rotator cuff injury, have
      neuropathic arthropathy. Syringomyelia should be included in the differential
      diagnosis of shoulder instability so that unnecessary and unsuccessful surgery
      can be avoided.

PMID- 22971610
TI  - Vincula of the biceps tendon in the glenohumeral joint: An arthroscopic and
      anatomic study.
AB  - An anatomic structure frequently observed during glenohumeral joint arthroscopy
      is described as the vincula of the long head of the biceps brachia tendon. These
      vincula were present in 24.3% of 411 shoulders (390 patients) undergoing shoulder
      arthroscopy. There was single vinculum in 56 shoulders, two vincula in 32, three
      in 12, and four in one shoulder. Younger age is a significant predictor of the
      presence of vincula. The presence of vincula was also related to subacromial
      impingement and glenoid labrum tearing. The absence of vincula was related to the
      diagnosis of rotator cuff tearing. The gross and microscopic structure is similar
      to the vincula of the finger flexor tendons.

PMID- 22971611
TI  - Thoracoglenoid fusion after subtotal scapulectomy.
AB  - Three cases of malignant tumors involving the scapula were treated primarily with
      a radical subtotal scapulectomy. Humeral head stabilization was achieved by
      fusion of the preserved neck of both the scapula and the glenoid to the chest
      wall, with good functional and cosmetic results.

PMID- 22971612
TI  - Computational analysis of thresholds for magnetophosphenes.
AB  - In international guidelines, basic restriction limits on the exposure of humans
      to low-frequency magnetic and electric fields are set with the objective of
      preventing the generation of phosphenes, visual sensations of flashing light not
      caused by light. Measured data on magnetophosphenes, i.e. phosphenes caused by a
      magnetically induced electric field on the retina, are available from volunteer
      studies. However, there is no simple way for determining the retinal threshold
      electric field or current density from the measured threshold magnetic flux
      density. In this study, the experimental field configuration of a previous study,
      in which phosphenes were generated in volunteers by exposing their heads to a
      magnetic field between the poles of an electromagnet, is computationally
      reproduced. The finite-element method is used for determining the induced
      electric field and current in five different MRI-based anatomical models of the
      head. The direction of the induced current density on the retina is dominantly
      radial to the eyeball, and the maximum induced current density is observed at the
      superior and inferior sides of the retina, which agrees with literature data on
      the location of magnetophosphenes at the periphery of the visual field. On the
      basis of computed data, the macroscopic retinal threshold current density for
      phosphenes at 20 Hz can be estimated as 10 mA m(-2) (-20% to + 30%, depending on
      the anatomical model); this current density corresponds to an induced eddy
      current of 14 MUA (-20% to + 10%), and about 20% of this eddy current flows
      through each eye. The ICNIRP basic restriction limit for the induced electric
      field in the case of occupational exposure is not exceeded until the magnetic
      flux density is about two to three times the measured threshold for
      magnetophosphenes, so the basic restriction limit does not seem to be
      conservative. However, the reasons for the non-conservativeness are purely
      technical: removal of the highest 1% of electric field values by taking the 99th
      percentile as recommended by the ICNIRP leads to the underestimation of the
      induced electric field, and there are difficulties in applying the basic
      restriction limit for the retinal electric field.

PMID- 22971613
TI  - 1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and
      downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway.
AB  - Cytochrome P4501B1 (CYP1B1) is responsible for tumor progression in estrogen
      receptor-positive breast cancer due to its key role in estrogen metabolism, which
      is upregulated by PGE2, the main product of COX-2 that is found to be
      overexpressed in many breast tumors. Previous studies reported that inhibition of
      the COX-2/PGE2 pathway, by 1,25-dihydroxyvitamin D3 in MCF-7 breast cancer cells.
      The aim of this study was to investigate if the CYP1B1 protein expression shows
      covariation with the COX-2 and phosphorylated ERalpha (p-ERalpha) in human breast
      cancer. We also investigated whether 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      downregulates CYP1B1 via the COX-2/PGE2 pathway in MCF-7 cells. We analyzed the
      expression of COX-2, p-ERalpha and CYP1B1 using an immunohistochemical staining
      assay. In the present study, COX-2 was correlated to p-ERalpha (P<0.001) and
      CYP1B1 (P=0.001), p-ERalpha was correlated to CYP1B1 (P=0.012). We assessed the
      effects of 1,25(OH)2D3 on MCF-7 cells. 1,25(OH)2D3 treatment inhibited MCF-7 cell
      growth in a time-and dose-dependent manner; the cell cycle was arrested in the
      G0/G1 phase. Treatment with 100 nmol/l 1,25(OH)2D3 for 72 h significantly
      decreased the expression of COX-2 mRNA in MCF-7 cells (P<0.05), decreased the
      levels of PGE2 in cell culture supernatant (P<0.01), and downregul-ated p-ERK, p
      ERalpha and CYP1B1 protein expression (P<0.05). Taken together, these results
      suggest that the COX-2/PGE2 pathway positively regulates the expression of CYP1B1
      in breast cancer. 1,25-Dihydroxyvitamin D3 inhibits the growth of MCF-7 cells and
      downregulates CYP1B1 mediated by the COX-2/PGE2 pathway.

PMID- 22971614
TI  - Testosterone replacement therapy in the setting of prostate cancer treated with
      radiation.
AB  - A lack of consensus and few data support testosterone replacement therapy (TRT)
      in hypogonadal men who have been treated for prostate cancer (CaP), particularly
      those who have received radiation therapy. We performed retrospective review of
      13 hypogonadal men with CaP, treated with brachytherapy or external beam
      radiotherapy who were subsequently treated with testosterone (T) between 2006 and
      2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG),
      prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values
      were evaluated approximately every 3 months after TRT initiation up to 67 months
      of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with
      Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation
      was 68.0 (62.0-77.0) years, initial T 178.0 (88.0-263.5) ng dl(-1), FT 10.1 (5.7
      15.0) pg ml(-1) and PSA 0.30 (0.06-0.95) ng ml(-1). Median follow-up after TRT
      initiation was 29.7 months (range 2.3-67.3 months). At median follow-up, a
      significant increase in mean T (368.0 (281.3-591.0) ng dl(-1), P=0.012) and SHBG
      were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66
      (0.16-1.35) ng ml(-1), P=0.345). No significant increases in PSA or CaP
      recurrences were observed at any follow-up interval. TRT in the setting of CaP
      after treatment with radiation therapy results in a rise in serum T levels and
      improvement in hypogonadal symptoms without evidence of CaP recurrence or
      progression.

PMID- 22971615
TI  - Combination therapy of testosterone enanthate and tadalafil on PDE5 inhibitor non
      reponders with severe and intermediate testosterone deficiency.
AB  - Several studies have suggested combination therapy with testosterone
      supplementation in patients not responding to PDE5 inhibitors. Considering the
      pathophysiological basis for testosterone supplementation, the present study aims
      to identify whether combination therapy allows persistence of treatment effect
      after testosterone discontinuation. Furthermore, we evaluated whether the degree
      of testosterone depletion affects treatment outcome from combination therapy.
      Hypogonadal patients (<350 ng dl(-1)) with erectile dysfunction who previously
      did not respond to PDE5 inhibitors were treated with testosterone enanthate
      injections and daily tadalafil. Patients were stratified into two groups
      depending on the level of testosterone deficiency, with 250 ng dl(-1) as a
      reference point. Following testosterone supplementation (12 weeks) and
      combination therapy (12 weeks), patients with severe testosterone deficiency
      showed higher IIEF (International Index of Erectile Function) erectile function
      (EF) domain score (16.47+/-4.019 vs 12.36+/-4.051, P=0.001) and more patients
      responding satisfactorily to treatment by general assessment (57.9 vs 16.0%,
      P=0.009), despite reaching similar levels of serum total testosterone (602+/-169
      ng dl(-1) vs 698+/-165 ng dl(-1), P=0.057). Testosterone supplementation was then
      discontinued and patients were maintained only on daily tadalafil (12 weeks). The
      severe depletion group maintained higher EF domain scores than baseline (13.06+/
      3.38 vs 7.20+/-2.24, P=0.0004), despite testosterone levels returning to
      baseline. The results suggest that combination therapy was more beneficial to
      patients with severe testosterone depletion, possibly by improving underlying
      pathophysiology.

PMID- 22971616
TI  - Associations of desire for change in sexual life amongst female medical students
      in North America.
AB  - We analyzed associations of dissatisfaction with sexual life and desire for
      change in female medical students. Students enrolled in medical schools in North
      America between February and July 2008 were invited to participate in an internet
      based survey of sexual function. The principle outcome measure was a single item
      question on sexual life satisfaction and desire for change. Women who reported
      dissatisfaction and desire for change were classified as 'sexually bothered'. The
      survey also assessed ethnodemographic factors, student status, sexual history and
      depressive symptoms. Respondents completed the Female Sexual Function Index
      (FSFI) and the Index of Sexual Life. Descriptive statistics, analysis of variance
      and multivariable logistic regression were utilized to analyze responses. There
      were 661 non-virgin female subjects with data adequate for analysis. Whereas 281
      (43%) of these met criteria for high risk of female sexual dysfunction (HRFSD)
      based on FSFI scoring, just 173 (26%) reported sexual bother. Among women with
      HRFSD, 126 (45%) reported sexual bother; in women without HRFSD, 362 (95%) were
      not sexually bothered. Interference in sexual life from tiredness and stress were
      associated with sexual bother. Progressively better scores on the FSFI desire,
      orgasm and satisfaction domains were significantly associated with lower odds of
      sexual bother. Few women in this cohort with FSFI score >26.55 reported sexual
      bother. Women with FSFI <26.55 had greater odds of sexual bother but this
      criterion alone was not pathognomonic for sexual concerns. Issues of sexual
      desire and orgasm appear to have a more important role than lubrication, arousal
      and sexual pain issues in this population.

PMID- 22971617
TI  - Acute myocardial infarction following a possible direct intravenous bite of
      Russell's viper (Daboia russelli).
AB  - BACKGROUND: Russell's viper (Daboia russelli) bites lead to high morbidity and
      mortality in South Asia. Although variety of clinical manifestations is reported
      in viper bite victims, myocardial ischemic events are rare. CASE PRESENTATION: We
      report a unique case of inferior wall ST elevation myocardial infarction due to a
      Russell's viper bite over a vein with possible direct intravenous envenoming, in
      a young male with no past history or family history suggestive of ischemic
      cardiac disease, from Sri Lanka. In addition, the possible mechanisms of
      myocardial ischemia in snake bite victims are also briefly discussed. CONCLUSION:
      Importance of the awareness of physicians on the rare, yet fatal manifestations
      of snake envenoming is highlighted.

PMID- 22971618
TI  - Concanavalin-A triggers inflammatory response through JAK/STAT3 signalling and
      modulates MT1-MMP regulation of COX-2 in mesenchymal stromal cells.
AB  - Pharmacological targeting of inflammation through STAT3 and NF-kappaB signaling
      pathways is, among other inflammatory biomarkers, associated with cyclooxygenase
      (COX)-2 inhibition and is believed to play a crucial role in prevention and
      therapy of cancer. Recently, inflammatory factors were found to impact on
      mesenchymal stromal cells (MSC) contribution to tumor angiogenesis. Given MSC
      chemotaxis and cell survival are regulated, in part, by the membrane type-1
      matrix metalloproteinase (MT1-MMP), an MMP also involved in transducing NF-kappaB
      intracellular signaling pathways, we tested whether STAT3 regulation by MT1-MMP
      may also contribute to the expression balance of COX-2 in MSC. We demonstrate
      that STAT3 phosphorylation was triggered in MSC treated with the MT1-MMP inducer
      lectin Concanavalin-A (ConA), and that this phosphorylation was abrogated by the
      JAK2 inhibitor AG490. MT1-MMP gene silencing significantly inhibited ConA-induced
      STAT3 phosphorylation and this was correlated with reduced proMMP-2 activation
      and COX-2 expression. On the other hand, STAT3 gene silencing potentiated ConA
      induced COX-2 expression, providing evidence for a new MT1-MMP/JAK/STAT3
      signaling axis that may, in part, explain how MT1-MMP contributes to
      proinflammatory intracellular signaling. Given that MSC are avidly recruited
      within inflammatory microenvironments and within experimental vascularizing
      tumors, these mechanistic observations support a possible dual control of cell
      adaptation to inflammation by MT1-MMP and that may enable MSC to be active
      participants within inflamed tissues.

PMID- 22971619
TI  - Integrin-linked kinase (ILK) modulates wound healing through regulation of
      hepatocyte growth factor (HGF).
AB  - Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix
      interactions and regulates many cellular processes, including growth,
      proliferation, survival, differentiation, migration, invasion and angiogenesis.
      The present work analyzes the role of ILK in wound healing in adult animals using
      a conditional knock-out of the ILK gene generated with the tamoxifen-inducible
      Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded
      wound closure in skin. Intracellular mechanisms involved in this process were
      analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice
      and revealed that wounding promotes rapid activation of phosphatidylinositol 3
      kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due
      to a decrease in cellular proliferation and loss of HGF protein expression during
      the healing process, in vitro and in vivo. Alterations in cell proliferation and
      wound closure in ILK-deficient MEF or mice could be rescued by exogenous
      administration of human HGF. These data demonstrate, for the first time, that the
      activation of PI3K and ILK after skin wounding are critical for HGF-dependent
      tissue repair and wound healing.

PMID- 22971620
TI  - Local spin density in the Cr7Ni antiferromagnetic molecular ring and 53Cr-NMR.
AB  - We present (53)Cr-NMR spectra collected at low temperature in a single crystal of
      the heterometallic antiferromagnetic (AF) ring Cr(7)Ni in the S = 1/2 ground
      state with the aim of establishing the distribution of the local electronic
      moment in the ring. Due to the poor S/N we observed only one signal which is
      ascribed to three almost equivalent (53)Cr nuclei in the ring. The calculated
      spin density in Cr(7)Ni in the ground state, with the applied magnetic field both
      parallel and perpendicular to the plane of the ring, turns out to be AF staggered
      with the greatest component of the local spin <s> for the Cr(3+) ions next to the
      Ni(2+) ion. The (53)Cr-NMR frequency was found to be in good agreement with the
      local spin density calculated theoretically by assuming a core polarization field
      of H(cp) = - 11 T/MU(B) for both orientations, close to the value found
      previously in Cr(7)Cd. The observed orientation dependence of the local spin
      moments is well reproduced by the theoretical calculation and evidences the
      importance of single-ion and dipolar anisotropies.

PMID- 22971621
TI  - Prosthetic replacement in rotator cuff-deficient shoulders.
AB  - We reviewed a series of 30 shoulders in 25 patients who had glenohumeral
      arthritis and rotator cuff deficiency and who underwent prosthetic replacement.
      Nineteen shoulders underwent humeral head replacement, and 11 shoulders had total
      shoulder arthroplasty. Meticulous mobilization and reconstruction of the
      deficiencies in the thin atrophic rotator cuff tissues were attempted in all
      shoulders. Emphasis was placed on anteroposterior stability, and this was
      achieved in all shoulders; superior coverage was fully achieved in 15 shoulders
      and was partially achieved in 11. All shoulders had less pain after surgery, and
      93% achieved satisfactory pain relief. Total shoulder arthroplasty and humeral
      hemiarthroplasty were found to provide similar results with respect to pain
      relief, functional improvement, and patient satisfaction. Shoulders with
      hemiarthroplasty gained significantly more active elevation (+52 degrees  vs + 2
      degrees ) after surgery. Cuff repair was easier when a humeral head prosthesis
      alone was used because less lateralization of the humerus occurred. Also,
      operative time, anesthesia time, and blood loss were decreased with
      hemiarthroplasty. Because the lack of glenoid resurfacing did not adversely
      affect pain relief or function and avoided the potential problem of glenoid
      loosening, we favor humeral hemiarthroplasty as a treatment for glenohumeral
      arthritis in the rotator cuff-deficient shoulder.

PMID- 22971622
TI  - Collagen type III in rotator cuff tears: An immunohistochemical study.
AB  - The presence and distribution of collagen type III, which represents newly formed
      fibers of early repair, were investigated in four surgically removed en bloc
      specimens of complete rotator cuff tears. The patients were two men and two women
      who ranged in age from 63 to 71 years. They had received preoperative,
      conservative treatment for a period varying from 3 months to 3 years. For the
      identification of the collagen immunohistochemical staining was performed by the
      peroxidase-antiperoxidase method with the use of monoclonal antibody against
      human collagen type III. Collagen type III was discernible throughout the tendon
      proper in all specimens. It often occurred in association with proliferating
      fibroblastic cells. Collagen type III was abundant only in the perivascular
      spaces of the much thickened bursal wall that extended over the margins of the
      tear. We concluded that the presence of collagen type III indicates the need for
      a continued attempt for repair at the site of the tear, including both bursal and
      tendinous tissues.

PMID- 22971623
TI  - The anatomy of the proximal radioulnar joint.
AB  - This study is an anatomic investigation to define the architecture of and the
      stabilizing structures for the proximal radioulnar joint. Ten fresh-frozen
      cadaver elbows were dissected. Measurements of the radial head, annular ligament,
      radial fossa of the ulna, and interosseous membrane were made and were correlated
      to clinical observations of elbow stability. Sequential transection of the soft
      tissue constraints of the proximal radioulnar joint demonstrated the annular
      ligament and the central band of the interosseous membrane to be the main
      stabilizers in pronation and the central band to be the significant stabilizer in
      supination. Eccentric loading of the joint was noted on anterior-posterior
      shifting of the radial head during forearm rotation. The clinical relevance of
      these observations in relation to radial head dislocation, fracture pattern, and
      elbow stability is discussed.

PMID- 22971624
TI  - Inferior capsular shift for inferior and multidirectional instability of the
      shoulder in young children: Report of two cases.
AB  - The literature contains few reports of shoulder multidirectional instability in
      young children and no reports of surgical treatment of this condition in young
      children. This article presents the case reports of a 4-year-old girl and an 8
      year-old girl who were treated with Neer's inferior capsular shift procedure. The
      surgical results of these patients remained good 4 and 5 years after the
      procedure, respectively. Surgical correction of multidirectional instability of
      the shoulder in a child should be performed only if the following indications are
      present: (1) the patients must have severe multidirectional instability, (2) the
      instability must have a significant negative impact on their daily activities,
      (3) the children must be able to understand the significance of the instability,
      and (4) school attendance and school participation must be compromised by the
      instability.

PMID- 22971625
TI  - Anatomic study of the glenoid labrum.
AB  - Thirty-one shoulder joints from the cadavers of 13 men and four women and from
      two cadavers of unspecified sex were dissected to investigate the anatomic
      characteristics of the glenoid labrum. The ages at death ranged from 63 to 90
      years with a mean age of 78.5 years. The glenoids were divided with a bone saw
      along both their long and short axes. The size of the glenoid and the labrum of
      each specimen was then measured with calipers. No significant correlation existed
      between the size of the labrum and that of the glenoid. This indicated that even
      if the glenoid was large, the labrum was not always correspondingly large. If one
      aspect of the labrum was large, other portions of the labrum tended to be large
      also. The anterior and inferior portions of the labrum were the largest, and this
      may have contributed to stability in the anterior and inferior directions.

PMID- 22971626
TI  - Development of pseudarthrosis in a dysplastic clavicle: A variant of congenital
      pseudarthrosis?
AB  - The development of a pseudarthrosis is reported in a child's right clavicle,
      which was previously noted to have been morphologically abnormal. Such
      pseudarthroses are uncommon, but they usually appear on the right side and may
      rarely be bilateral. The differential diagnosis is of a postpartum fracture, a
      posttraumatic pseudarthrosis, cleidocranial dysostosis, or neurofibromatosis. A
      review of the development of the clavicle and the hypotheses for such anomalous
      development are given.

PMID- 22971627
TI  - Codman's paradox: Sixty years later.

PMID- 22971628
TI  - Letter to the editor.

PMID- 22971629
TI  - Robotic bariatric surgery: bypass, band and sleeve. Where are we now? And what is
      the future?
AB  - Rates of Obesity and Bariatric surgery continue to increase worldwide. Obese
      patients represent a unique cohort with important anatomical and physiological
      challenges that can influence operative outcome. The aim of this review is to
      evaluate the current evidence regarding the role of robotics in bariatric
      surgery. Robotic surgery confers several technical advantages including better
      visual field with improved three-dimensional image, seven degrees of freedom and
      anti-tremor filters to enable more precise manipulations and increased dexterity
      by downscaling the surgeon's movements. These technical advantages are more
      likely to confer a benefit in terms of clinical outcome in more complicated
      minimally invasive procedures especially gastric bypass and in particular with
      important steps of the procedure such as anastomotic suturing. Despite these
      advantages robotic bariatric surgery is associated with increased cost and
      operative time, which may limit its use in less complicated procedures such as
      gastric band surgery. Future highly powered randomized controlled trials are
      required to accurately evaluate clinical outcome and cost-effectiveness of
      robotics both in gastric bypass and in sleeve gastrectomy.

PMID- 22971630
TI  - Role of robotic surgery in colorectal resections for cancer.
AB  - In recent years, robotic surgery is becoming a valid alternative in colorectal
      diseases treatment to laparoscopic and traditional open surgery. The most
      relevant reported technical advantages of the robotic surgery are 3D-view, tremor
      filtering, seven degree-free motion and a higher comfortable setting for the
      surgeon. Both case series and comparative studies available in Literature report
      only short and mid-term outcomes. These studies are able to demonstrate that
      robotic surgery is as safe and feasible as laparoscopic surgery regarding
      perioperative outcomes. Trials with long term follow up are needed to establish
      the real safety and effectiveness of the robotic surgery especially concerning
      resections for cancer. The robotic surgery could be considered a promising
      surgical field. The high costs represent one of the most relevant drawbacks.

PMID- 22971631
TI  - Minimally invasive colorectal surgery.
AB  - Adoption of laparoscopic colorectal surgery has been slow. In the United States,
      of approximately 250,000 colectomies each year, only 5% to 15% of these cases are
      being done laparoscopically. Laparoscopic colorectal surgery can be performed
      successfully on patients for both benign and malignant conditions in any anatomic
      location of the colon and rectum. The COST trial definitively established that
      laparoscopic colon surgery for cancer had similar rates of local recurrence and
      survival compared to open surgery, with better short-term outcomes. It
      demonstrated that laparoscopic resections resulted in shorter hospital stays,
      decreased IV narcotics and oral analgesics, and improved quality of life within
      two weeks of surgery. In the authors' clinical experience of more than 1500
      laparoscopic surgeries, patients who undergo laparoscopic colorectal surgery
      experience decreased rates of wound infection, hernia, and bowel obstruction. One
      of the challenges of laparoscopic colorectal surgery is standardizing these
      complex, minimally invasive procedures in the operating room. With standard
      techniques, one can create optimal outcomes for patients, minimizing
      perioperative complications and maximizing oncologic results. This paper
      describes a sequenced step approach for each procedure to facilitate this. Left
      colectomy follows a nine-step process, and right colectomy follows a four-step
      process. Both of these procedures are described in detail. The newest horizon in
      minimally invasive surgery is single incision surgery, which allows for
      colorectal resections through a single 2.5 cm incision, producing an excellent
      cosmetic result. Based on this chapter, we advocate the laparoscopic approach be
      used as the primary method for colorectal surgery.

PMID- 22971632
TI  - Single port laparoscopic colorectal surgery in debilitated patients and in the
      urgent setting.
AB  - Single port laparoscopy is a relatively new niche in the expanding spectrum of
      minimal access surgery for colorectal disease. To date the published experience
      has predominantly focused on planned operations for neoplasia in the elective
      setting. It seems probable however that the benefits of minimal abdominal
      wounding will be greatest among those patients with the highest risk of impaired
      wound healing. Combining this with the impression of improved cosmesis suggests
      that (the mostly young) patients with inflammatory bowel disease needing urgent
      operation are the most likely to appreciate and benefit from the extraoperative
      effort. The extension of single port surgery to the acute setting and for
      debilitated individuals is therefore a likely next step advance in broadening the
      category of patients for whom it represents a real benefit and ultimately aid in
      focusing by selection the subgroups for whom this technique is best suited and
      most appropriate. We describe here our approach (including routine use of a
      surgical glove port) to patients presenting for urgent colorectal operation for
      benign disease. As provision of specialized approaches regardless of timing or
      mode of presentation is a defining component of any specialty service, this
      concept will soon be more fully elucidated and established.

PMID- 22971633
TI  - Medical and surgical management of esophageal and gastric motor dysfunction.
AB  - he occurrence of esophageal and gastric motor dysfunctions happens, when the
      software of the esophagus and the stomach is injured. This is really a program
      previously established in the enteric nervous system as a constituent of the
      newly called neurogastroenterology. The enteric nervous system is composed of
      small aggregations of nerve cells, enteric ganglia, the neural connections
      between these ganglia, and nerve fibers that supply effectors tissues, including
      the muscle of the gut wall. The wide range of enteric neuropathies that includes
      esophageal achalasia and gastroparesis highlights the importance of the enteric
      nervous system. A classification of functional gastrointestinal disorders based
      on symptoms has received attention. However, a classification based solely in
      symptoms and consensus may lack an integral approach of disease. As an
      alternative to the Rome classification, an international working team in Bangkok
      presented a classification of motility disorders as a physiology-based diagnosis.
      Besides, the Chicago Classification of esophageal motility was developed to
      facilitate the interpretation of clinical high-resolution esophageal pressure
      topography studies. This review covers exclusively the medical and surgical
      management of the esophageal and gastric motor dysfunction using evidence from
      well-designed studies. Motor control of the esophagus and the stomach, motor
      esophageal and gastric alterations, treatment failure, side effects of PPIs,
      overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD
      medical management, data related to conservative treatment vs. antireflux
      surgery, and postsurgical esophagus and gastric motor dysfunction are also taken
      into account.

PMID- 22971634
TI  - Current status of laparoscopic distal pancreatectomy.
AB  - Distal pancreatectomy is the therapeutic option of choice for patients with a
      benign or malignant lesion located in the body and/or tail of the pancreas when
      surgical intervention is indicated. With recent advances in and wide spread use
      of imaging studies, lesions of the pancreas are being diagnosed more commonly and
      it is likely that this will translate into an increased number of patients
      undergoing surgical resection. The laparoscopic approach to pancreatic resections
      has not been adopted as rapidly as it has for most other general surgical
      procedures. This is despite the fact that the current literature appears to
      validate laparoscopy as an acceptable and safe approach for distal pancreatectomy
      in patients with benign lesions, and has demonstrated the known benefits inherent
      to the laparoscopic technique. These benefits include lower intraoperative blood
      loss, less pain and analgesic requirements, earlier return of bowel function, and
      shorter recovery and hospital stay. Yet controversy still exists for the role of
      laparoscopy in the resection of malignant lesions. Recent reports however, have
      shown that laparoscopic distal pancreatectomy can safely be performed in known
      malignancies and, most importantly, after a laparoscopic oncological resection,
      the oncological benchmarks that have been related to survival, (such as negative
      surgical margins and number of peripancreatic lymph nodes resected), can also be
      accomplished. We sought to review the current literature on distal
      pancreatectomy, specifically the indications, laparoscopic approaches,
      splenectomy and spleen-preserving techniques, intraoperative and short-term
      outcomes, morbidity, mortality and oncological outcomes.

PMID- 22971635
TI  - Nutritional intervention for amyotrophic lateral sclerosis.
AB  - AIM: The aim of the study was to assess the consequences of early and systematic
      nutritional intervention on the clinical conditions of amyotrophic lateral
      sclerosis (ALS) patients and on the opportunity to maintain a good nutritional
      status for as long as possible. METHODS: Thirty-three subjects with ALS. Protocol
      Group: 12 subjects (9 M and 3 F) monitored according to a precise nutritional
      intervention protocol. CONTROL GROUP: 21 subjects (10 M and 11 F) monitored
      before applying the protocol. RESULTS: Data recorded at the time of initial
      assessment were compared and expressed as the mean +/- standard deviation for the
      Protocol Group vs. the CONTROL GROUP: BMI (kg/m2) 23.6 +/- 4.1 vs. 21.6 +/- 3.5;
      weight loss as a percentage of usual weight 6.6 +/- 7.9 vs. 16.3 +/- 8.8
      (P=0.003). At six months: weight loss as a percentage of usual weight 4.9 +/- 6.2
      vs. 16.9 +/- 10.2 (P=0.002). At 12 months: weight loss as a percentage of usual
      weight 7.3 +/- 7.1 vs. 17.5 +/- 11.1 (P=0.03). At the first follow-up visit,
      fewer patients in the Protocol Group were receiving enteral nutrition (25%) than
      patients in the CONTROL GROUP (60%). At six-month follow-up visit: 30% vs. 68%.
      Standard enteral nutrition formulas were used. One year after initial assessment,
      the mortality rate was 17% for the Protocol Group, whereas it was 24% at six
      months and 33% after one year for the CONTROL GROUP. CONCLUSION: If patients are
      treated before any significant weight loss occurs, early and specific nutritional
      intervention allows good nutritional status to be maintained for a longer period;
      if artificial nutrition is required, standard diets are able to ensure adequate
      clinical results.

PMID- 22971636
TI  - New techniques in imaging in Barrett's esophagus.
AB  - The presence of dysplasia in patients with Barrett's esophagus identifies who is
      at increased risk for the development of esophageal adenocarcinoma and who may
      most benefit from intervention. Several technologies have emerged as potent tools
      to identify subtle or occult neoplasia in the gastrointestinal tract. Detailed
      inspection of the mucosa with high resolution white light endoscopy is the most
      critical tool to detect subtle neoplasia. This review also chromoendoscopy,
      narrow band imaging, autofluorescence imaging, optical coherence tomography,
      confocal laser endomicroscopy, and spectroscopy in the context of detection of
      neoplasia in Barrett's esophagus.

PMID- 22971637
TI  - Transanal endoscopic surgery using single access and standard laparoscopic
      instrumentation.
AB  - Transanal endoscopic microsurgery (TEM) or operation (TEO) refer to the concept
      of performing intraluminal excision of rectal lesions with specialized, high
      specification equipment that maintains a stable pneumorectum and allows either
      high definition or binocular optical visualization of the target site along with
      the capacity for using precise instrumentation (including electocautery) for
      tissue tensioning, dissection, resection and re-apposition. However, neither
      technology is widely available and capital set-up costs are high. Furthermore,
      the rigid, elongated cylindrical configuration of the rectoscope can prove
      restrictive for non-expert practitioners in that it demands a rarefied and
      hitherto relatively non-transferrable skill-set only achievable with high volume
      caseloads. The advent of single port minimally invasive surgery arising on a
      broadened background of widespread advanced laparoscopic skills and equipment
      among colorectal departments along with an increasing incidence of appropriate
      lesions (either large dysplastic tumors or early and neoadjuvantly downstaged
      rectal cancers) may, however, provide the means for this approach to become more
      integrated into mainstream practice by the removal of these barriers for
      interested practitioners. While early generation devices still need adaption for
      perfect applicability to transanal access and oncologic standards need to be
      carefully maintained in parallel with increased proliferation of technical
      capacity, the transfer of single port techniques and access platforms to
      transanal work has great potential through the convergence of practice of these
      two niche applications. Here we present a detailed analysis of currently
      available single port devices (including the table-side constructed "Glove TEM
      Port") in transanal application and define the ideal parameters required to make
      this a reality.

PMID- 22971638
TI  - RL66 a second-generation curcumin analog has potent in vivo and in vitro
      anticancer activity in ER-negative breast cancer models.
AB  - There is a need for the development of new safe and efficacious drug therapies
      for the treatment of estrogen receptor (ER)-negative breast cancers. 1-Methyl-3,5
      bis[(E)-4-pyridyl)methylidene]-4-piperidone (RL66) is a second generation
      curcumin analog that exhibits potent cytotoxicity towards a variety of ER
      negative breast cancer cells. Therefore, we have further examined the mechanism
      of this novel drug in in vitro and in vivo models of ER-negative breast cancer.
      The mechanistic studies demonstrated that RL66 (2 uM) induced cell cycle arrest
      in the G2/M phase of the cell cycle. Moreover, RL66 (2 uM) caused 40% of SKBr3
      cells to undergo apoptosis after 48 h and this effect was time-dependent. This
      correlated with an increase in cleaved caspase-3 as shown by western blot
      analysis. RL66 (2 uM) also decreased HER2/neu phosphorylation and increased p27
      in SKBr3 cells, while in MDA-MB-231 and MDA-MB-468 cells RL66 (2 uM)
      significantly decreased Akt phosphorylation and transiently increased the stress
      kinases JNK1/2 and MAPK p38. In addition, RL66 exhibited anti-angiogenic
      potential in vitro as it inhibited HUVEC cell migration 46% and the ability of
      these cells to form tube-like networks. RL66 (8.5 mg/kg) suppressed the growth of
      MDA-MB-468 xenograft tumors by 48% compared to vehicle control following 10 weeks
      of daily oral administration. Microvessel density in the tumors from treated mice
      was also decreased 57% compared to control. Thus our findings demonstrate that
      RL66 has potent proapoptotic and anti-angiogenic properties in vivo and in vitro
      and has the potential to be further developed as a drug for the treatment of ER
      negative breast cancer.

PMID- 22971639
TI  - A single nucleotide polymorphism of reduced folate carrier 1 predicts
      methotrexate efficacy in Japanese patients with rheumatoid arthritis.
AB  - Methotrexate (MTX) exhibits large inter-individual and inter-ethnic differences
      in the dose required for its anti-rheumatic effect. To maintain low disease
      activity, patients may require increased MTX doses or co-administration of
      biologic disease-modifying anti-rheumatic drugs (bDMARDs). The availability of a
      marker predicting the effect of MTX will make it possible to increase the MTX
      dose and prescribe bDMARDs to patients at an early stage. To establish
      individualized medication for rheumatoid arthritis (RA), we investigated genetic
      polymorphisms of the folate pathway in Japanese RA patients. Eighty-nine patients
      were treated with MTX alone (MTX group). MTX and bDMARDs were co-administered to
      81 patients because of insufficient MTX efficacy (MTX + bDMARDs group); an
      equally stable therapeutic effect was achieved in both groups. Polymorphism
      analyses using bDMARD co-treatment as the objective variable revealed a
      significant association between age and the G80A polymorphism of the reduced
      folate carrier 1 gene (RFC1) as an explanatory variable. Compared to patients
      with the A allele, patients with the G allele may have less intracellular MTX
      uptake and, therefore, poor efficacy; a greater number of them were found to be
      bDMARD concomitant cases. The results of this study suggest that the RFC1 G80A
      polymorphism may be a useful marker for predicting MTX efficacy in Japanese
      patients with RA.

PMID- 22971640
TI  - Cost-effectiveness analysis of microdose clinical trials in drug development.
AB  - Microdose (MD) clinical trials have been introduced to obtain human
      pharmacokinetic data early in drug development. Here we assessed the cost
      effectiveness of microdose integrated drug development in a hypothetical model,
      as there was no such quantitative research that weighed the additional
      effectiveness against the additional time and/or cost. First, we calculated the
      cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug
      development strategies: liquid chromatography-tandem mass spectrometry,
      accelerator mass spectrometry, and positron emission tomography. Then, we
      analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug
      candidates entering into a non-clinical toxicity study were selected by different
      methods as the conventional scenario without MD. In the base-case, where 70 drug
      candidates were selected without MD and 30 selected evenly by one of the three MD
      methods, incremental cost-effectiveness ratio per one additional drug approved
      was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness
      ratio of the conventional strategy was JPY 24.4 billion, which we set as a
      threshold. Integrating MD in the conventional drug development was cost-effective
      in this model. This quantitative analytical model which allows various
      modifications according to each company's conditions, would be helpful for
      guiding decisions early in clinical development.

PMID- 22971642
TI  - Analysis of the pharmacokinetic boosting effects of ritonavir on oral
      bioavailability of drugs in mice.
AB  - Ritonavir dramatically increases the bioavailability of a variety of
      concurrently administered drugs by inhibition of metabolic enzymes and drug
      transporters. The purpose of this study was to investigate the extent to which
      ritonavir's inhibition of drug transporters and/or CYP3A contributes to the
      increased oral bioavailability in mice. The area under the plasma concentration
      time curves (AUC) for orally administered saquinavir after coadministration with
      50 mg/kg ritonavir dramatically increased (325-fold). As a result, the
      bioavailability, Fa.Fg and Fh increased 75-, 38- and twofold, respectively. In
      addition, the increase in the AUC predicted from the in vitro Ki value was
      ninefold, which was derived from the inhibition of metabolic enzymes by ritonavir
      in the liver. The remaining 36-fold increase in the AUC was considered to be
      derived from the inhibition in the small intestine. The AUCinf for probe
      substrate midazolam, fexofenadine, and pravastatin increased after the oral
      administration of ritonavir by only five-, 13-, and sevenfold, respectively.
      Moreover, the AUC0-12 for saquinavir was affected negligibly by itraconazole.
      These results indicate ritonavir mainly affects the first-pass effect of
      saquinavir in the small intestine, increasing the bioavailability of orally
      administered saquinavir. Furthermore, cyp isoforms other than CYP3A, which
      contribute to the metabolism of saquinavir in humans, are involved in the
      metabolism of saquinavir in mice.

PMID- 22971641
TI  - MDR1 C3435T polymorphism and interaction with environmental factors in risk of
      Parkinson's disease: a case-control study in Japan.
AB  - It has been suggested that P-glycoprotein (P-gp), the product of multidrug
      resistance 1 (MDR1) gene, regulates the brain entry of various xenobiotics.
      Impaired function of P-gp may be associated with an increased risk of Parkinson's
      disease (PD). The aim of this study was to investigate the impact of a MDR1
      C3435T polymorphism on PD risk alone or in combination with environmental
      factors. A total of 238 patients with PD and 368 controls were genotyped for the
      MDR1 C3435T polymorphism. Subjects with the TT genotype of the C3435T
      polymorphism showed a nonsignificantly increased risk of PD [odds ratio
      (OR)=1.49, 95% confidence interval (CI)=0.85-2.25] compared with those with the
      CC genotype. A gene-environment interaction was suggested, with a combination of
      at least one T allele and ever drinking conferring significantly higher risk
      (OR=1.83, 95% CI=1.07-3.15, p=0.029), compared with the CC genotype and never
      drinking. No significant interaction of smoking or occupational pesticide use
      with the C3435T polymorphism was observed. Our results suggest that the C3435T
      polymorphism may not play an important role in PD susceptibility in Japanese.
      Evidence of an interaction between the C3435T polymorphism and alcohol
      consumption was suggested.

PMID- 22971643
TI  - Battery-triggered microfluidic paper-based multiplex electrochemiluminescence
      immunodevice based on potential-resolution strategy.
AB  - A potential-resolution strategy for multiplex electrochemiluminescence (ECL)
      immunoassay on a microfluidic paper-based analytical device (MU-PAD) was
      demonstrated for the first time, using tris-(bipyridine)-ruthenium(ii)
      (Ru(bpy)(3)(2+)) and carbon nanodots (CNDs) as the ECL labels for high-throughput
      ECL immunoassay on MU-PAD. Based on this strategy, simultaneous detection of four
      tumor markers using only two screen-printed carbon working electrodes (one
      electrode for two analytes) on an immunodevice consisting of a piece of patterned
      paper (denoted as MU-PECLI in this work) was realized, which is a simplification
      of the configuration of traditional MU-PADs. As a further development of MU-PECLI
      in low-cost and disposable applications, battery-triggered (constant-potential)
      ECL detection on MU-PECLI was developed, allowing the traditional electrochemical
      workstation to be abandoned. In addition, to exactly control the output voltage
      of the battery, a low-cost and simple voltage-controller was designed and
      fabricated for the first time. The battery-triggered ECL immunoassay principle on
      MU-PECLI is explained. We found that the simultaneous determination of two
      analytes in one paper working zone could be achieved by controlling the
      operational constant-potential (+1.2 V for Ru(bpy)(3)(2+) labels and -1.2 V for
      CNDs labels (vs. Ag/AgCl auxiliary electrode)) by simply reversing the connection
      mode. Finally, four tumor markers in human serum samples from the Tumor Hospital
      were assayed and the results obtained were in acceptable agreement with the
      reference values from parallel single-analyte test. This battery-triggered MU
      PECLI provides a new strategy for high-throughput, low-cost, sensitive, automated
      and simultaneous multiplex immunoassay and point-of-care diagnosis.

PMID- 22971644
TI  - Ultrasound-guided peripheral intravenous placement with standard-length catheters
      and long catheters.

PMID- 22971645
TI  - Hanging Pt hollow nanocrystal assemblies on graphene resulting in an enhanced
      electrocatalyst.
AB  - Pt hollow nanostructures assembled by nanocrystals were in situ grown and hung
      onto graphene layers to combine the merits from favorable catalyst morphology
      control and synergetic improvement effect of the graphene support, resulting in a
      composite with enhanced electrocatalytic performance.

PMID- 22971647
TI  - Lack of detection of host associated differences in Newcastle disease viruses of
      genotype VIId isolated from chickens and geese.
AB  - BACKGROUND: The goose is usually considered to be resistant even to strains of
      Newcastle disease virus (NDV) that are markedly virulent for chickens. However,
      ND outbreaks have been frequently reported in goose flocks in China since the
      late 1990s with the concurrent emergence of genotype VIId NDV in chickens.
      Although the NDVs isolated from both chickens and geese in the past 15 years have
      been predominantly VIId viruses, published data comparing goose- and chicken
      originated ND viruses are scarce and controversial. RESULTS: In this paper, we
      compared genotype VIId NDVs originated from geese and chickens genetically and
      pathologically. Ten entire genomic sequences and 329 complete coding sequences of
      individual genes from genotype VIId NDVs of both goose- and chicken-origin were
      analyzed. We then randomly selected two goose-originated and two chicken
      originated VIId NDVs and compared their pathobiology in both geese and chickens
      in vivo and in vitro with genotype IV virus Herts/33 as a reference. The results
      showed that all the VIId NDVs either from geese or from chickens shared high
      sequence homology and characteristic amino acid substitutions and clustered
      together in phylogenetic trees. In addition, geese and chickens infected by goose
      or chicken VIId viruses manifested very similar pathological features distinct
      from those of birds infected with Herts/33. CONCLUSIONS: There is no genetic or
      phenotypic difference between genotype VIId NDVs originated from geese and
      chickens. Therefore, no species-preference exists for either goose or chicken
      viruses and more attention should be paid to the trans-species transmission of
      VIId NDVs between geese and chickens for the control and eradication of ND.

PMID- 22971649
TI  - Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute
      respiratory syndrome coronavirus.
AB  - The papain-like protease (PL(pro)), which controls replication of the severe
      acute respiratory syndrome coronavirus (SARS-CoV), has been identified as a
      potential drug target for the treatment of SARS. An intensive hunt for effective
      anti-SARS drugs has been undertaken by screening for natural product inhibitors
      that target SARS-CoV PL(pro). In this study, diarylheptanoids 1-9 were isolated
      from Alnus japonica, and the inhibitory activities of these compounds against
      PL(pro) were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed
      the most potent PL(pro) inhibitory activity, with an inhibitory concentration
      (IC(50)) value of 4.1 uM. Structure-activity analysis showed that catechol and
      alpha,beta-unsaturated carbonyl moiety in the molecule were the key requirement
      for SARS-CoV cysteine protease inhibition.

PMID- 22971648
TI  - Hyperin and quercetin modulate oxidative stress-induced melanogenesis.
AB  - Hyperin and quercetin are phenolic compounds present in fruits and vegetables
      that have been reported to possess strong anti-oxidative properties. Although
      increasing evidence strongly suggests that antioxidants suppress the melanin
      synthesis that is causally associated with oxidative stress, the protective
      actions of hyperin and quercetin against oxidative stress-induced melanogenesis
      have not been fully explored. To elucidate the suppressive effects of hyperin and
      quercetin on oxidative stress and melanin synthesis, peroxynitrite (ONOO(-))
      scavenging activity was measured in vitro as were quantifications of melanin
      content, intracellular total RS, ONOO(-), superoxide ((*)O(2)), nitric oxide
      (NO(*)), catalase activity and the reduced glutathione (GSH)/oxidized glutathione
      (GSSG) ratio. Results showed that in vitro, hyperin and quercetin reduced ONOO(
      ). Additionally, hyperin and quercetin suppressed total RS, ONOO(-), (*)O(2), and
      NO(*), catalase activity, and melanin synthesis, while they boosted the GSH/GSSG
      ratio in B16F10 melanoma cells (B16 cells). Therefore, I propose that hyperin and
      quercetin have a powerful capacity to modulate oxidative stress-induced
      melanogenesis.

PMID- 22971650
TI  - [Assessment of somatic development and body composition in the 7th year of life
      in children born as extremely low birth weight infants (<=1000g); a multi-centre
      cross-sectional study of a cohort born between 2002 and 2004 in the Malopolska
      voivodship].
AB  - Children born with extremely low birth weight often present delayed growth in the
      first years of their lives: they remain shorter and weigh less than their peers.
      Current reports published worldwide state that later in life these children are
      at an increased risk of cardiac and vascular diseases, diabetes and obesity.
      Abnormal distribution and the excess of fat tissue predispose them to develop the
      metabolic syndrome. THE AIM of the study was to evaluate the somatic development
      of seven-year-old children born with birth-weight <=1000 g (ELBW) in the
      Malopolska voivodship and to estimate the content and distribution of fat tissue.
      Moreover, the risk factors of disturbed somatic development were evaluated.
      MATERIALS AND METHODS: Two hundred and four live newborns with birth weight
      <=1000 g were born in the Malopolska voivodship between 1.09.2002 and 31.08.2004.
      One hundred and fifteen of these children (56%) died in early infancy. The study
      included 81 children in the 7th year of life out of the 89 surviving ones. Their
      mean gestational age at birth was 27.3 weeks. (SD: 2.1 weeks) and their mean
      birth-weight was 840 g (SD: 130 g). All the children underwent anthropometric
      measurements and the thickness of the skin fold over the triceps was measured.
      Body mass index (BMI) was calculated and the body composition was assessed by
      multifrequency bioimpedance. The control group consisted of 39 children born at
      term chosen randomly from the general population and matched with regard to age
      and sex. RESULTS: The ELBW children in the 7th year of life were shorter (z
      score: -1.06+/-1.4 p<0.001), had lower body mass (z-score: -0.57+/-0.9; p=0.01),
      smaller head circumference (z-score: -1.2+/-1.3; p<0.001), lower BMI (z-score: 
      0.99+/-1.6; p<0.001) as compared to their peers. Fat tissue mass was lower in the
      ELBW group than in the control group (11% vs 16%; p<0.01). The most retarded
      somatic development was observed in the group of children suffering from cerebral
      palsy. CONCLUSIONS: 1. Children born with ELBW, at 7 years of life, present
      significantly retarded somatic development as compared with their full-term
      peers. 2. The most important risk factor of somatic development disturbances is
      cerebral palsy. 3. Children born with low birth weight and ELBW, need long term
      follow up.

PMID- 22971651
TI  - [Causes of short stature in children in relation to their midparental height].
AB  - INTRODUCTION: It is considered that the evaluation of a child's height strongly
      depends on the evaluation of his/her midparental height. AIM OF STUDY: Analysis
      of causes of short stature in children in relation to midparental height.
      MATERIAL AND METHODS: The study included 452 children with short stature, aged 3
      18 yrs. The group of children included 178 girls and 274 boys. The children's
      measurements were standardized using the arithmetic mean and standard deviation
      for the Institute of Mother and Child norms. Midparental height was evaluated
      according to standards for 18-year-olds. The average height deficit was -2.5
      SDS+/-0.65. The average midparental height was 166.07 cm+/-4,63 and in SDS it was
      -0.93+/-0,74. RESULTS: Growth hormone deficiency (GHD) or multihormonal pituitary
      deficiency was found in 34.3% of the patients (50 girls and 105 boys). In 22
      girls (12.48) the Turner syndrome (TS) was diagnosed. Other causes of short
      stature were observed in 37 children. No hormonal disorders were found in the
      remaining group (275 children). 7% of those children were characterized by
      significant height deficit (-3 SDS). The difference between midparental height of
      GHD children and healthy children was not statistically significant. Body height
      of 20% of GHD children was consistent with their midparental height. The
      midparental height of girls with TS was significantly higher than the midparental
      height of the other children. The body height of 50% of girls with TS differed
      from their midparental height. The body height of 40% of healthy short children
      was consistent with their midparental height. CONCLUSIONS: 1. Children with short
      stature are a very heterogenous group of patients. 2. Comprehensive evaluation of
      physical development in children should not be restricted to the widely used
      criterion of midparental height.

PMID- 22971652
TI  - [The frequency of risk factors for atherosclerosis in youth aged 16 and 18 years-
      students of upper-secondary schools in Poland].
AB  - OBJECTIVES: 1. To examine the prevalence of selected risk factors for
      atherosclerosis: overweight, tobacco smoking, low physical activity,
      psychological distress and type A personality (characterized by tenseness,
      impatience, competitiveness, and aggressiveness) in adolescents and to assess the
      frequency the coexistence of risk factors (>=3) in relation to gender, age and
      school type. METHODS: A cross-sectional study was carried out in a representative
      sample of youth aged 16 and 18 years (N=2983) in 8 voivodeships in Poland. The
      frequency of five atherosclerosis risk factors and their coexistence (>=3) was
      examined using self-reported questionnaires, in relation to gender, age and
      school type. Logistic regression analyses were used to assess the influence of
      the variables (gender, age and school type) on odds ratios of risk factor
      coexistence. RESULTS: Low physical activity was the most common risk factor,
      statistically more frequent in students from Basic Vocational Schools than in
      other school types (p<0.05). In Basic Vocational Schools there was also the
      highest percentage of cigarette smokers (p<0.001). Psychological distress and
      type A behaviour were observed most frequently in students from General Upper
      Secondary Schools. The highest risk factor accumulation (>=3) was observed among
      students from Basic Vocational Schools (40%), significantly more frequent in
      girls than boys (47.5% and 37.5% respectively). Multivariable analyses show that
      students from Basic Vocational Schools had twice the odds (OR=2.25, p<0.001) to
      have the coexistence of risk factors for atherosclerosis as compared with
      students from General Upper Secondary Schools, girls had almost twice as many
      occurrences (OR=1.83, p<0.001) as boys and 18-year-olds 1.5 more than 16-year
      olds (OR=1.46, p<0.001). CONCLUSION: 1. A significant difference in the
      prevalence of risk factors for atherosclerosis in youth from different school
      types requires precise definition of priority health promotion activities
      depending on school type. 2. Students from Basic Vocational Schools should be the
      target group for intervention aimed at reducing atherosclerosis risk factors.

PMID- 22971653
TI  - [Can the concentration of immunomodulating factors in mature breastmilk be
      associated with food allergy in breastfed children?].
AB  - OBJECTIVES: The aim of the study was to determine the concentration of such
      immunomodulating factors as transforming growth factor beta1 (TGF-beta1),
      interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) in mature human
      milk and to relate the levels of the above mentioned cytokines in mature breast
      milk to the occurence of food allergy in children during the first 24 months of
      life. MATERIALS AND METHODS: Data on breastfeeding, symptoms of food allergy in
      children and breast milk samples were collected prospectively from birth to 24
      months of age from 84 mothers participating in the Polish birth cohort of
      "EuroPrevall" study, in the years 2005-2007. Cytokine levels were measured in the
      whey with commercial enzyme-linked immunosorbent assays (ELISA) kits. RESULTS:
      Ten out of the eighty four (11.9%) participating children had positive SPT and/or
      sIgE to food antigens. In 7 out of 84 (8.4%) children DBPCFC confirmed the
      diagnosis of food allergy. The median concentration of TGF-beta1 was 21.94 pg/ml
      (range 10.47-83.19), TNF-alpha 1.46 pg/ml (range 0.35-16.50), IL- 101.83 pg/ml
      (range 0.58-31.04). There was a positive correlation between the concentration of
      IL-10 and TGF-beta1. The level of TNF-alpha correlated positively with the
      duration of lactation (p=0.04). There was no significant difference between the
      concentration of IL-10, TGF-beta1, TNF-alpha, in the mature breast milk of
      mothers of children with symptoms of allergy and positive SPT and/or sIgE,
      mothers of children with positive DBPCFC and in the milk of mothers of control
      children. CONCLUSIONS: There was no significant difference between the
      concentration of IL-10, TGF-beta1, TNF-alpha, in the mature breast milk of
      mothers of children with food allergy and in the breast milk of mothers of
      control children.

PMID- 22971655
TI  - [Assessment of selected bone metabolism marker concentrations in children with
      cystic fibrosis].
AB  - AIM: The aim of this study was to assess bone formation and resorption processes
      and bone metabolism regulators, such as osteoprotegerin and fetuin-A in children
      with cystic fibrosis. MATERIAL AND METHODS: We examined 45 children with cystic
      fibrosis aged 5-13 years treated at the Institute of Mother and Child in Warsaw.
      The control group consisted of 35 healthy children in the same synage range
      without any diseases which may influence bone metabolism. We determined serum
      calcium and phosphate levels by colorimetric methods, vitamin D3 by the
      chemiluminiscence method and bone metabolism markers (osteocalcin, 5b isoenzyme
      of tartrate-resistant acid phosphatase, osteoprotegerin, fetuin-A) by
      immunoenzymatic methods. RESULTS: Mean serum concentrations of calcium and
      phosphate in the studied children were within the reference ranges. However, the
      level of 25-hydroxyvitamin D3 was significantly lower in patients with cystic
      fibrosis compared to the controls (19.3+/-7.6 vs 25.2+/-8.9 ng/ml, p<0.01). In
      cystic fibrosis children we observed a statistically significant lower
      concentration of osteocalcin (81.9+/-28.9 vs 97.9+/-28.6 ng/ ml, p<0.01) and
      similar activity of 5b isoenzyme of tartrate-resistant acid phosphatase (12.5+/
      2.9 vs 13.4+/-3.5 U/L) as compared to healthy peers. Mean serum concentration of
      osteoprotegerin in patients with CF was significantly lower than in the control
      children (4.1+/-0.98 vs 4.59+/-0.86 pmol/l, p<0.05). Serum concentration of
      fetuin-A was comparable in both groups of children. CONCLUSIONS: In children with
      cystic fibrosis changes in the profile of bone metabolism markers were observed.
      Even patients with CF who are clinically stable and supplemented with vitamins
      are at risk of osteopenia and osteoporosis in their later life. Therefore, they
      should be under a comprehensive medical and nutritional care in order to achieve
      their optimal peak bone mass.

PMID- 22971656
TI  - [Atypical celiac disease--diagnostic difficulties].
AB  - In predisposed individuals dietary intake of cereal products may lead to the
      development of food allergy or celiac disease. These diseases may also coexist
      with each other. In recent years, a change in the clinical picture of celiac
      disease has been observed and the incidence of atypical forms has increased. The
      disease is currently either diagnosed late or often remains undiagnosed. The
      article presents a case of an underweight 11- year old girl with height
      deficiency and recurrent respiratory infections, as well as chronic rhinitis,
      occurring from the age of three. On the basis of complex differential diagnosis,
      sensitization to tree pollens, and to cow's milk protein and gluten were
      identified. Despite the detection of antibodies specific for celiac disease, such
      as the antibodies against smooth muscle endomysium (IgAEMA) and anti-tissue
      transglutaminase antibodies (IgAtTGAb), the histological confirmation of the
      diagnosis was not obtained. Implementation of the gluten and milk protein-free -
      elimination diet and the use of antihistamines resulted in clinical improvement
      and the disappearance of markers of both food sensitization and celiac disease.
      The second food provocation test was negative for previously detected markers of
      food sensitization but showed the presence of IgAEMA and IgAtTGAb and the
      histological features of intestinal mucosa typical for celiac disease.
      CONCLUSIONS: The diagnosis of food allergy or other chronic diseases which can
      cause growth disturbance (short stature and/or impaired weight gain ) should not
      exempt from the obligation of estimating the markers specific for celiac disease.

PMID- 22971654
TI  - [The evaluation of selected parameters of calcium and phosphorus metabolism in
      children with cow's milk allergy].
AB  - THE AIM of this study was to evaluate selected parameters of calcium and
      phosphorus metabolism in children with CMA treated with the following milk
      substitute formulas: lactose-containing extensively hydrolyzed wheat protein
      formula, lactose-free extensively hydrolyzed casein protein formula, as well as
      soy-based formula. MATERIAL AND METHODS: The study involved 66 children with CMA
      aged 2-5 years treated with milk-free diet for at least one year. Group I
      included 31 children fed with a lactose-containing formula, group II - 35
      children treated with lactose-free formula. In all children the mean energy
      intake and nutritional value of daily food rations were assessed. Serum
      concentrations of calcium (Ca), phosphorus (P), sodium (Na) and magnesium (Mg)
      were determined using standard methods. Serum values of 25 hydroxyvitamin D (25
      OH D) and parathormone (PTH) were assessed by chemiluminescence, whereas
      concentrations of biochemical markers of bone formation-bone alkaline phosphatase
      (BALP), osteocalcin (OC) and bone resorption marker-collagen type I crosslinked C
      telopeptide (CTX) were determined by immunoenzymatic methods (ELISA), using
      specific monoclonal antibodies. RESULTS: There were no significant differences in
      the mean dietary supply of calcium, phosphorus, magnesium, sodium, total protein
      and vitamin C in children from both groups. In the diets of children from group
      II, the mean content of lactose (0.5+/-1.0 vs 10.0+/-6.8 g/d) and 25-OH vitamin D
      (4.1+/-2.3 vs 8.5+/-4.0 ug/d) were significantly lower and dietary fibre content
      (14.7+/-3.9 vs 10.4+/-3.9 g/d) was higher. Calcium and vitamin D dietary supply
      was lower with respect to nutritional recommendations in all the studied
      children, whereas the dietary deficiency of vitamin D was higher in children from
      group II. The mean serum concentrations of evaluated biochemical parameters did
      not reveal any differences in children from the study groups and were in the
      normal ranges. There were also no differences in the mean serum concentration of
      25-OH vitamin D, ALP, BALP, CTX and PTH in patients from both groups. The mean
      concentration of OC was significantly higher in group II (71+/-26.6 ng/ml) than
      in children from group I (61.1+/-23.4 ng/ml) <0.01. Positive correlation was
      found between OC and CTX in both study groups. CONCLUSIONS: 1. In children with
      CMA basic blood laboratory tests may have limited importance in the evaluation of
      calcium and phosphorus metabolism. 2. Our results suggest that the disturbances
      in the balance between bone formation and bone resorption processes may occur in
      children with CMA treated with lactose-free formulas. 3. In order to assure
      optimal conditions for achieving adequate bone mass by children with CMA, it is
      necessary to provide them with regular medical and nutritional care.

PMID- 22971657
TI  - [Late sequelae of central nervous system prophylaxis in children with acute
      lymphoblastic leukemia: high doses of intravenous methotrexate versus
      radiotherapy of the central nervous system--review of literature].
AB  - Acute lymphoblastic leukemia is the most common malignancy in children. All
      current therapy regimens used in the treatment of childhood acute lymphoblastic
      leukemia include prophylaxis of the central nervous system. Initially it was
      thought that the best way of central nervous system prophylaxis is radiotherapy.
      But despite its effectiveness this method, may cause late sequelae and
      complications. In the programme currently used in Poland to treat acute
      lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy)
      and is used only in patients stratified into the high risk group and in patients
      diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal
      methotrexate is given alone or in combination with cytarabine and hydrocortisone
      is given, as well as systemic chemotherapy with intravenous methotrexate is
      administered in high or medium doses (depending on risk groups and leukemia
      immunophenotype). Recent studies have shown that high dose irradiation of the
      central nervous system impairs cognitive development causing memory loss,
      visuomotor coordination impairment, attention disorders and reduction in the
      intelligence quotient. It has been proved that the degree of cognitive impairment
      depends on the radiation dose directed to the medial temporal lobe structures,
      particularly in the hippocampus and the surrounding cortex. Also, methotrexate
      used intravenously in high doses, interferes with the metabolism of folic acid
      which is necessary for normal development and the optimal functioning of neurons
      in the central nervous system. It has been proved that patients who have been
      treated with high doses of methotrexate are characterized by reduced memory
      skills and a lower intelligence quotient. The literature data concerning long
      term neuroanatomical abnormalities and neuropsychological deficits are ambiguous,
      and there is still no data concerning current methods of central nervous system
      prophylaxis with low doses of irradiation in combination with high doses of
      intravenous methotrexate.

PMID- 22971658
TI  - [Diagnostic difficulties in Smith-Magenis Syndrome (SMS) on the basis of own
      experience and literature data].
AB  - The Smith-Magenis syndrome (SMS) is a rare microdeletion dysmorphic syndrome
      (interstitial microdeletion of chromosome 17p11.2), which occurs sporadically.
      Mutations in the RAI1 gene are found in part of the patients. SMS is
      characterized by intellectual disability and behavioural disturbances (sleep
      disturbances, hyperactivity, attention deficit, self-injury behaviour),
      craniofacial dysmorphism and defects of other organs and systems (teeth, eyes and
      upper respiratory and hearing disturbances, short stature, brachydactyly,
      scoliosis, cardiac and genitourinary defects). There are also neurological
      problems (muscular hypotonia, peripheral neuropathy, epilepsy and decreased
      sensitivity to pain). Many of the features that appear in the SMS may occur in
      other genetic syndromes, which may cause diagnostic difficulties. We report two
      cases of late diagnosed patients with the Smith-Magenis syndrome. Additionally,
      we present a review of literature and differential diagnosis. This may help in
      making the diagnosis and in giving optimal medical and psychological care to
      patients with SMS.

PMID- 22971659
TI  - [Precocious puberty in a vertically HIV-infected girl].
AB  - The authors present the case of a vertically HIV infected, six-year-old girl,
      with precocious puberty. The late diagnosis of HIV both in the mother and in the
      child is of significance. Different causes of adrenarche precox are also
      discussed. In pediatric practice vertical HIV infection should be taken into
      consideration in differential diagnosis. In routine care of HIV-infected
      children, monitoring of development including sexual development is indicated.
      The presence of symptoms of adrenarche precox, as in noninfected children needs
      in depth diagnostic investigations. The role of HIV infection and of
      antiretrovirus treatment in the pathogenesis of adrenarche precox remains unclear
      and needs further investigation.

PMID- 22971660
TI  - [Mother-to-child HBV transmission--atypical course of hepatitis B in an infant].
AB  - The article presents the course of hepatitis B transmitted from mother to her
      child. In the nine-week-pregnant mother HBsAg was not detected, but five months
      after delivery chronic stage hepatitis B was diagnosed. The infant was vaccinated
      twice against HBV without HBIG. At six months of age, the infant developed acute
      hepatitis B and Gianotti-Crosti syndrome (GCS) with high level of
      aminotransferase activity. In the 2nd year of life seroconversion in the HBe
      system and reduction of hepatitis B activity was observed. CONCLUSIONS: 1. The
      double HBsAg test in pregnant women may increase the detectability of HBV
      infection. 2. Current prophylaxis of HBV infection is not sufficient to protect
      mother-to-child transmission. 3. Spontaneous regression of acute hepatitis B in
      infants may occur in the period of more than 6 months from the onset, that is in
      the chronic stage.

PMID- 22971661
TI  - Acute appendicitis in children under 3 years of age. Diagnostic and therapeutic
      problems.
AB  - AIM: Analysis of diagnostic and therapeutic problems in acute appendicitis in
      children below 3 years of age. MATERIAL AND METHODS: The analysis was based on
      medical data of 53 children under 3 years of age, treated in our department for
      acute appendicitis in the years 1988-2008. Among 53 children, 29 (53.7%) were
      admitted directly to the surgical department and 24 (45.3%) were transferred from
      the regional pediatric department. In the period of 1 month before admission to
      the surgical department 13 patients (24.5%) were treated as outpatients due to
      acute respiratory or alimentary tract infection. On the basis of the data from
      the case histories, the most frequent symptoms and their duration were evaluated,
      as well as the clinical signs, intraoperative diagnosis and the postoperative
      course. RESULTS: The most frequent symptoms and clinical signs in this group of
      children were: abdominal pain, vomiting and fever, present in 83.0%, 75.5%, and
      67.0% patients respectively. The mean time of the symptoms' duration was 3.6
      days. The most frequently found physical signs on admission to the surgical ward
      were: abdominal pain on palpation, increased tonus of abdominal muscles and
      abdominal distension. On laparotomy gangrenous appendicitis was found in 49% of
      the children operated. In 24.5% of patients perforation of the appendix was
      confirmed. Further complications occurred in 9 children (16.9%). The average stay
      in hospital after the operation lasted 7.9 days. CONCLUSIONS: 1. Acute
      appendicitis in small children is a diagnostic problem not only for primary
      health care doctors but also for experienced pediatricians and pediatric
      surgeons. 2. Early surgical consultation should be a standard procedure in small
      children with acute symptoms of various locations when there is accompaning
      abdominal pain, not reacting to conservative treatment. Surgical consultation is
      also indicated in children under 3 years of age with relapses of abdominal pain.
      3. Clinical signs of appendicitis in children aged less than 3 years, may differ
      from those in older children due to changes in their immunological reactivity.
      This problem should be included in under-graduate and post-graduate medical
      studies.

PMID- 22971662
TI  - Interleukin-9 release from human kidney grafts and its potential protective role
      in renal ischemia/reperfusion injury.
AB  - OBJECTIVE AND DESIGN: The pathophysiology of ischemia/reperfusion (I/R) injury is
      dominated by an inflammatory response. In the identification of new therapeutic
      agents, the role of individual cytokines may be essential. Interleukin (IL)-9 is
      a pleiotropic cytokine recently identified to be involved in various immune
      responses. In this study, the role of IL-9 in renal I/R injury was assessed.
      METHODS: We performed repeated direct measurements of arteriovenous IL-9
      concentration differences over the reperfused graft in human kidney
      transplantation. RESULTS: Substantial renal IL-9 release was observed from
      deceased donor kidneys (P = 0.006). In contrast, living donor kidneys, which have
      a more favourable clinical outcome, did not release IL-9 during early reperfusion
      (P = 0.78). Tissue expression of IL-9 did not change upon reperfusion in both
      living and deceased human donor kidneys. To assess the role of IL-9 in I/R
      injury, an experimental study comprising IL-9 inhibition in mice undergoing renal
      I/R was performed. Although there was no difference in kidney function,
      structural damage was significantly aggravated in anti-IL-9 treated mice.
      CONCLUSIONS: Deceased donor grafts show a substantial IL-9 release upon
      reperfusion in clinical kidney transplantation. However, inhibition of IL-9
      aggravated kidney damage, suggesting a regulating or minor role of IL-9 in
      clinical I/R injury.

PMID- 22971663
TI  - Cytotoxic effects of Echinacea purpurea flower extracts and cichoric acid on
      human colon cancer cells through induction of apoptosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea is a top-selling herbal supplement that
      acts as immunostimulant. It has been used to treat common cold, coughs,
      bronchitis and upper respiratory infections. It is also a popular product used in
      anticancer therapy. The cytotoxic effects of Echinacea on cancer cells are still
      not clear. The aims of this study were to provide a preliminary validation of the
      effects of 50% aqueous ethanol extract of Echinacea purpurea flowers and its
      major compound, cichoric acid, on human colon cancer cells Caco-2 and HCT-116.
      MATERIALS AND METHODS: The cytotoxic effects of Echinace flower extracts and
      cichoric acid on cell viability, telomerase activity, DNA fragmentation, beta
      catenin, caspase-9, and cleavage of poly-ADP-ribose polymerase (PARP) of human
      colon cancer cell were examined. RESULTS: The results showed a significant
      inhibition of proliferation in E. purpurea flower extract and cichoric acid in a
      dose- and time-dependent manner. Cichoric acid treatment decreased telomerase
      activity in HCT-116 cells. Moreover, cichoric acid effectively induced apoptosis
      in colon cancer cells, which were characterized by DNA fragmentation, activation
      of caspase-9, cleavage of PARP and downregulation of beta-catenin. CONCLUSIONS:
      Our data indicate that cichoric acid has a strong growth-inhibitory effect
      against colon cancer cells, presumably resulting from the reduced telomerase
      activity and the induction of apoptosis. The exact mechanism of action should
      still be determined in future studies. Overall, the effects of 50% aqueous
      ethanol extract of E. purpurea flowers and cichoric acid may have provided in
      vitro evidence for the use as chemotherapeutic agents.

PMID- 22971664
TI  - Estimation of neutron-equivalent dose in organs of patients undergoing
      radiotherapy by the use of a novel online digital detector.
AB  - Neutron peripheral contamination in patients undergoing high-energy photon
      radiotherapy is considered as a risk factor for secondary cancer induction. Organ
      specific neutron-equivalent dose estimation is therefore essential for a
      reasonable assessment of these associated risks. This work aimed to develop a
      method to estimate neutron-equivalent doses in multiple organs of radiotherapy
      patients. The method involved the convolution, at 16 reference points in an
      anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy
      spectra with the kerma and energy-dependent radiation weighting factor. This was
      then scaled with the total neutron fluence measured with passive detectors, at
      the same reference points, in order to obtain the equivalent doses in organs. The
      latter were correlated with the readings of a neutron digital detector located
      inside the treatment room during phantom irradiation. This digital detector,
      designed and developed by our group, integrates the thermal neutron fluence. The
      correlation model, applied to the digital detector readings during patient
      irradiation, enables the online estimation of neutron-equivalent doses in organs.
      The model takes into account the specific irradiation site, the field parameters
      (energy, field size, angle incidence, etc) and the installation (linac and bunker
      geometry). This method, which is suitable for routine clinical use, will help to
      systematically generate the dosimetric data essential for the improvement of
      current risk-estimation models.

PMID- 22971666
TI  - Modified loop technique in three dogs with mitral regurgitation.
AB  - Mitral valvuloplasty (MVP) is used in dogs with refractory mitral regurgitation
      (MR); however, it is difficult to tie the artificial chord, i.e., the expanded
      polytetrafluoroethylene suture, at the planned height of the mitral valve,
      because of the slippery nature of the knot. The loop technique has resolved these
      difficulties in humans. Premanufactured loops (length, 8.0-15.0 mm with 1.0-mm
      increments) were used in the new modified loop technique. In the current study,
      cardiac murmurs disappeared, and the MR markedly improved or completely
      disappeared approximately 3 months after surgery in 3 dogs. Therefore, this new
      technique might be effective in dogs.

PMID- 22971667
TI  - Association of puppies' behavioral reaction at five months of age assessed by
      questionnaire with their later 'Distraction' at 15 months of age, an important
      behavioral trait for guide dog qualification.
AB  - Guide dogs help visually impaired persons both physically and psychologically.
      More than half of all candidate dogs do not qualify, mainly for behavioral
      reasons. Improved training efficacy is desirable, and earlier prediction of
      qualification-related traits would be beneficial. In a previous study, we
      identified 'Distraction', assessed during the training period, as an important
      behavioral trait for judging the qualification of guide dogs at the Japan Guide
      Dog Association. As a second step, we aimed to develop an index that can predict
      during the puppy period. In this study, candidate guide dogs, 5-month-old
      Labrador retrievers, were assessed by puppy raisers using a newly developed
      questionnaire that consisted of 20 items. The same dogs were assessed later, at
      15 months, by trainers to determine 'Distraction'. In principal components
      analysis, nine items, including excitability toward strangers, initiative while
      out for a walk, and exploration, composed the first principal component (PC1).
      When we compared PC1 points with 'Distraction' points, the two categories were
      positively correlated (n=110, r(s)=0.31, P=0.0009). Although the accuracy of the
      questionnaire should be increased, the results of the present study suggest that
      it may be possible to assess and predict 'Distraction', which is associated with
      disqualification for guide dogs, early in the puppy-raising period.

PMID- 22971665
TI  - Cardiomyocytes derived from human induced pluripotent stem cells as models for
      normal and diseased cardiac electrophysiology and contractility.
AB  - Since the first description of human induced pluripotent stem cell-derived
      cardiomyocytes (hiPSC-CMs), these cells have garnered tremendous interest for
      their potential use in patient-specific analysis and therapy. Additionally, hiPSC
      CMs can be derived from donor cells from patients with specific cardiac
      disorders, enabling in vitro human disease models for mechanistic study and
      therapeutic drug assessment. However, a full understanding of their
      electrophysiological and contractile function is necessary before this potential
      can be realized. Here, we review this emerging field from a functional
      perspective, with particular emphasis on beating rate, action potential, ionic
      currents, multicellular conduction, calcium handling and contraction. We further
      review extant hiPSC-CM disease models that recapitulate genetic myocardial
      disease.

PMID- 22971668
TI  - Effect of emergency oral contraceptive use on condom utilization and sexual risk
      taking behaviours among university students, Northwest Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Young people between the ages of 15 and 24 years are both the most at
      risk of HIV and the greatest hope for turning the tide against HIV/AIDS. Although
      various surveys have been done on sexual behaviour of youth in Ethiopia, studies
      assessing the effect of emergency oral contraceptives on condom utilization of
      university students are lacking. METHODS: A cross-sectional study was conducted
      in two major universities of Ethiopia from January to May 2011 using structured
      self administered questionnaire with the aim to assess the effect of introducing
      oral emergency contraceptive pills on condom utilization and sexual risk taking
      behaviours among female university students. Study participants were selected by
      simple random sampling using the list from the associate registrars of each
      University. Data were entered, cleaned and analyzed using SPSS version 17.0.
      Bivariate and multiple logistic regression analyses were used to determine
      factors associated with condom utilization. RESULTS: a total of 623 students out
      of 660 were included giving response rate of 94.4%. A total of 103(16.5%) had
      history of sexual intercourse and nearly half (45.6%) of them had sex before the
      age of 20 years. Forty (6.4%) students had history of sexually transmitted
      infections (STI). Sixty seven percent of students had heard about emergency oral
      contraceptives. One hundred and ninety one (45.7%) of students believe that EOC
      is effective in preventing pregnancy. Believing that EOC is effective in
      preventing pregnancy (adjusted Odds ratio, AOR = 0.22 95% CI 0.06, 0.87), condom
      prevents STI (AOR = 10.37, 95% CI 1.73, 62.24) and younger age below 20 years
      (AOR = 11.68 95% CI 1.25, 109.19) were statistically significantly associated
      with condom use. CONCLUSION: a significant number of students had history of
      sexual intercourse and used emergency contraception. The belief in the
      effectiveness of EOC negatively affects condom use. The preference for the pill
      may make teenagers less prepared to practice STI protective behaviours in
      specific situations. Therefore, there is an urgent need to educate young people
      in universities about reproductive health and family planning and skills on how
      to prevent HIV/STIs including unwanted pregnancy.

PMID- 22971670
TI  - Ten-year assessment of primary rotator cuff repairs.
AB  - A review of 30 patients who underwent a primary repair of their rotator cuff 10
      years previously was performed. The average age of the patients at the time the
      operation was performed was 51 years (range 20 to 65 years). Twenty-seven men and
      three women were reviewed. An acromioplasty was performed in all patients. No
      patient had a distal clavicle excision. There were 12 small, 11 medium, five
      large, and two massive tears. A significant decrease in pain after surgery and a
      return to preinjury activities occurred in 82% of the patients. Subjective
      results were excellent or good in 70% of the patients. Good or excellent results
      were achieved in 80% of the 25 patients with objective data. In the overall
      results (subjective and objective), 64% of the patients had a good or excellent
      outcome. By Neer's criteria, 72% satisfactory results were achieved. No
      significant prognostic indicators were identified in this study, although a trend
      toward better results occurred in patients less than 55 years old and in those
      patients with smallor medium-sized tears. The findings of this study confirm the
      view that the results of rotator cuff repairs do not deteriorate, with follow-up
      extending to 10 years.

PMID- 22971669
TI  - Efficacy and safety of duloxetine 30 mg/d in patients with fibromyalgia: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of duloxetine 30 mg/d in adults
      with fibromyalgia. METHODS: This 12-week, randomized, double-blind, placebo
      controlled study was conducted in the United States, Mexico, Argentina, and
      Israel and enrolled patients meeting the criteria for primary fibromyalgia as
      defined by the American College of Rheumatology. The primary endpoint was the
      average pain severity item from the Brief Pain Inventory (BPI)-Modified Short
      Form, assessed by an analysis of covariance model using change from baseline to
      the modified baseline-observation-carried-forward endpoint. Secondary endpoints
      included the Patient Global Impression of Improvement (PGI-I) score and the
      Fibromyalgia Impact Questionnaire (FIQ) total score and those measuring pain,
      depression, anxiety, health outcomes, and safety. RESULTS: Patients (mean age, 51
      y; 95% female; 87% White; 22% with major depressive disorder) received duloxetine
      30 mg/d (N=155) or placebo (N=153). Duloxetine-treated patients did not have a
      statistically significant BPI-Modified Short Form average pain severity reduction
      versus placebo-treated patients (-2.04 vs. -1.70; P=0.202). There was a
      significant difference between duloxetine-treated and placebo-treated patients
      (P<0.05) for the PGI-I endpoint score (2.97 vs. 3.35) and the changes in FIQ
      total score (-14.62 vs. -9.75) and the Short-Form Health Survey (SF)-36 mental
      component score. Discontinuations due to adverse events did not differ
      significantly between treatment groups; nausea and dry mouth were the only
      adverse events with a significantly higher incidence with duloxetine versus
      placebo. DISCUSSION: Duloxetine 30 mg/d did not significantly reduce pain
      severity in patients with fibromyalgia. However, duloxetine-treated patients
      reported global improvement in symptoms and function. Safety findings were
      consistent with the known duloxetine safety profile.

PMID- 22971671
TI  - Rotator cuff tears in the patient with paraplegia.
AB  - Shoulder problems are common in patients with paraplegia because of long-term
      weight bearing that occurs when crutches or wheelchairs are used and when
      transfers are done. Two moderate and two large rotator cuff tears in three
      patients with paraplegia were operated on and evaluated with the use of our
      shoulder assessment system. A special roentgenographic projection designated as a
      "push-up view" was used after the operation for evaluation. It is an
      anteroposterior projection of both shoulders on a large casette and is done while
      the patient lifts himself or herself up with extended elbows off the seat of an
      armchair. The operative methods employed were anterior acromioplasty in all
      shoulders, tenorrhaphy in two, lateral transfer of the tendon of the long head of
      the biceps brachii (Bush procedure) in two with large tears, and superior
      capsular reconstruction with the use of an autogenous fascia lata graft for a
      recurrent large tear. The results were satisfactory in three shoulders and
      unsatisfactory in the shoulder with the recurrent tear. To relieve pain and
      preserve function in the patient with paraplegia, especially during transfers,
      early recognition of the cuff tear, a meticulous repair, and rehabilitation are
      essential. The "push-up" view is useful for assessment of the integrity of the
      rotator cuff.

PMID- 22971672
TI  - The structure and function of the coracohumeral ligament: An anatomic and
      microscopic study.
AB  - Twelve fresh-frozen cadaver shoulders were dissected to study the anatomy and
      histology of the coracohumeral ligament. Based on the gross and microscopic
      anatomy, the ligament was found in three variations. In the most common pattern
      (nine of 12 specimens), the coracohumeral ligament represented a folded portion
      of glenohumeral joint capsule in the rotator interval between subscapularis and
      supraspinatus. Because of its inverted "v"-shaped origin from the coracoid base,
      tension on this structure creates the appearance of a prominent ligamentous
      structure. However, histologic cross-sections of this pattern of coracohumeral
      ligament reveal that it is lined by synovium on its undersurface and contains no
      discretely organized collagen bundles representative of a ligament. The second
      pattern (two of 12 specimens) was similar, except that the capsular reflection
      representing the ligament was fused together, giving the structure a more clearly
      definable anterior edge. In only one specimen was the ligament a truly
      ligamentous structure. In its normal state the coracohumeral ligament usually
      appears as a capsular reflection on the coracoid base, and though it courses
      toward the superior aspect of the intertubercular groove, it is not a true
      ligamentous structure. These findings support the position of those authors who
      state that the coracohumeral ligament is unlikely to play a significant role as a
      suspensory structure in its physiologic state.

PMID- 22971673
TI  - Osteoporosis of the proximal humerus: Comparison of bone-mineral density and
      mechanical strength with the proximal femur.
AB  - The hypothesis that the proximal humerus is more osteoporotic than the proximal
      femur has been examined by the indention test and bone-mineral density
      measurement on dissected proximal humeri and femora. The bone section at the base
      of the humeral head had about 65% of the bone-mineral density of the base of the
      femoral head. The energy required for 50% strain in the indention test on the
      humeral bone section was about 50% of that on the femoral head. The fact that the
      cancellous bone in the humeral head is more osteoporotic than in the femur may
      complicate surgical treatment of displaced humeral neck fractures.

PMID- 22971674
TI  - Modified-tension band wiring of displaced surgical neck fractures of the humerus.
AB  - Fifteen two-part surgical neck fractures of the humerus in 14 patients were
      treated with a modified-tension band wiring technique. In this technique, one
      wire is placed through the greater tuberosity and supraspinatus tendon, and the
      other wire is placed through the lesser tuberosity and subscapularis tendon. Each
      wire is connected to the shaft in a similar figure-of-eight technique. This
      places the wires approximately 90 degrees  apart from each other, with neither
      wire crossing over the biceps tendon. Four (26.7%) fractures had early loss of
      fixation, and one patient was lost to follow-up. Follow-up evaluation in the
      remaining 10 fractures (nine patients) averaged 33.4 months (range 26 to 53
      months). Clinically, there were three (30%) excellent results, five (50%)
      satisfactory results, one (10%) unsatisfactory result, and one (10%) failure with
      the rating scale described by Neer. Based upon these results we cannot recommend
      the tension band wiring technique used. We consider the high incidence of loss of
      fixation (26.7%) reported in this series to be unacceptable.

PMID- 22971675
TI  - Surgical and methodologic aspects of proximal humeral osteotomy for stabilization
      of the shoulder joint.
AB  - It has previously been shown that a small retroversion angle might predispose to
      recurrent anterior shoulder dislocation, and in patients with remaining
      instability after soft-tissue repair the retroversion angle is often reduced. In
      these patients a rotation osteotomy of the proximal humerus to correct the
      anatomy in order to stabilize the joint can be advocated. The surgical technique
      for subcapital rotational osteotomy of the humerus is presented in this report.
      An isolated humerus has been osteotomized and radiographically examined in
      various positions. These findings, supplemented with mathematic calculations of
      the relationship between shift in millimeters of the osteotomy and angle of
      correction, have provided guidelines for obtaining accurate correction of the
      humeral head retroversion angle at surgery. The method has been used in seven
      patients with recurrent anterior shoulder dislocations, and all patients were
      operated on with a rotational osteotomy. Mean retroversion before surgery was 15
      degrees . It was changed after surgery to a mean value of 32 degrees . All
      shoulders became stable and pain-free and had a normal range of motion. At the 3
      year follow-up no radiologic signs of osteoarthrosis were found.

PMID- 22971676
TI  - Superoinferior translation in the intact and vented glenohumeral joint.
AB  - The purpose of this investigation was to measure inferior translation in the
      intact and vented shoulder in different positions of abduction and rotation.
      Fifteen shoulders from adult cadavers were tested before and after venting of the
      joint capsule on an apparatus that permitted unconstrained translation when a 50
      N inferior force was applied to the humeral shaft. The greatest inferior
      translation in the intact shoulder occurred at 45 degrees  abduction in neutral
      rotation. Venting the capsule significantly increased inferior translation in all
      positions but 45 degrees  abduction, and the greatest effect was seen at 0
      degrees  glenohumeral abduction in neutral rotation. The so-called "sulcus sign"
      is the result of intraarficular vacuum effect and capsular laxity. Venting the
      capsule results in a significant increase in inferior translation. This is an
      important effect to consider during procedures for repairing instability of the
      shoulder, because failure to appreciate the normal "play" in inferior
      glenohumeral translation might lead the surgeon to believe that perceived laxity
      represents actual instability.

PMID- 22971677
TI  - Shoulder arthroscopy with the use of local anesthesia.
AB  - In recent years shoulder arthroscopy has become increasingly used. To simplify
      the procedure and to minimize cost and operative risks, a study has been
      conducted to evaluate the use of local anesthesia for diagnostic shoulder
      arthroscopy. Two groups of patients were studied. The first group of 17 patients
      was examined while the patients were under general anesthesia, but a continuous
      infusion of lidocaine-chloride 0.2% was also performed. Serial blood samples were
      obtained. In all patients the peak serum level of local anesthetic was below the
      toxic levels. Seventeen other patients were operated on while they were under
      local anesthesia; 20 ml 1% prilocaine-epinephrine was injected into the soft
      tissues on the posterior aspect of the shoulder, and a continuous infusion of
      0.2% lidocaine-chloride was infused intraarticularly during the procedure. In
      addition, adjunctive diazepam was used in eight patients. Three patients could
      not complete the procedure because of pain. We conclude that the absorption
      pattern of local anesthetic from the shoulder joint during arthroscopy is within
      the acceptable dose range. However, performing diagnostic shoulder arthroscopy
      with the patient under local anesthesia is a demanding procedure for the patient
      and may not always be possible.

PMID- 22971678
TI  - Suprascapular nerve compression by a ganglion cyst: Diagnosis by magnetic
      resonance imaging.

PMID- 22971680
TI  - Peritoneal dialysis and cardiovascular disease.
AB  - Cardiovascular (CV) death is the most frequent cause of dying in peritoneal
      dialysis (PD) patients. Risk factors include not only those that can be present
      in the general population, but also those related to the presence of end-stage
      renal disease (ESRD) and factors that are specific for PD modality. Hypertension
      is the most important general risk factor in PD patients, while obesity remains
      controversial. Inflammation, malnutrition, calcifications and probably
      endothelial dysfunction and oxidative stress are all CV risk factors present in
      ESRD that contribute to mortality in PD patients. Additional CV risk factors in
      PD are related to the glucose load, leading to increasing insulin resistance and
      a more atherogenic lipid profile. The presence of glucose degradation products in
      conventional dialysis solutions is mainly related to the development of
      peritoneal abnormalities, but not directly to cardiovascular disease. Loss of
      residual renal function and ultrafiltration failure promote overhydration, which
      is the most important PD-related risk factor for CV disease.

PMID- 22971679
TI  - Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in
      patients with hepatocellular carcinoma.
AB  - Dendritic cells (DCs) are increasingly used as adjuvants for vaccination
      strategies; however, there has been very little development in DC vaccines for
      patients with hepatocellular carcinoma (HCC). In this study, we assessed the
      safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)
      pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by
      culturing blood monocytes in the presence of granulocyte macrophage-colony
      stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by
      pulsing DCs with cytoplasmic transduction peptide-attached alpha-fetoprotein,
      glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the
      presence of maturation cocktail. DCs were injected subcutaneously near the
      inguinal lymph nodes, followed by topical application of toll-like receptor-7
      agonist around the injection site. We showed that our DC vaccine was safe and
      well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell
      responses against TAAs. Clinical benefit was observed in one of the 5 patients.
      In conclusion, the feasibility, safety and immune activity of DCs pulsed with
      TAAs were confirmed in HCC patients. However, clinical response was detected only
      in one patient. Future trials may consider applying this therapy in a less
      advanced stage to obtain better clinical responses.

PMID- 22971681
TI  - Peritoneal dialysis in patients with heart failure.
AB  - Both in dialysis patients and non-uremic patients heart failure is associated
      with an adverse prognosis. In a state of abrupt worsening of cardiac function,
      acute cardiogenic shock or decompensated congestive heart failure, acute kidney
      injury may occur, whereas in a more chronic worsening of cardiac function chronic
      kidney injury may occur. Recently, the term cardiorenal syndrome was adopted and
      defined as "a pathophysiological disorder of the heart and kidneys whereby acute
      or chronic dysfunction in one organ may induce acute or chronic dysfunction in
      the other organ". Despite better treatment techniques and the continuous
      development of new medications volume overload in patients with cardiorenal
      syndrome is difficult to treat. Especially treatment of cardiorenal syndrome type
      I and II is notoriously difficult. Peritoneal dialysis might be, because of the
      gradual fluid removal, a therapeutic option in these patients. However, data on
      the effect of peritoneal dialysis in patients with heart failure with fluid
      overload and/or renal impairment are scarce. In this review, the role of
      peritoneal dialysis in the treatment cardiorenal syndrome type I, II and IV will
      be discussed.

PMID- 22971682
TI  - Dialysis in diabetic patients: hemodialysis and peritoneal dialysis. Pros and
      cons.
AB  - Both hemodialysis (HD) as well as peritoneal dialysis (PD), are efficient renal
      replacement therapies in uremic patients with and without diabetes. PD is less
      expensive dialysis modality and may provide a survival advantage over
      hemodialysis in first 2 to 4 years of treatment. Chronic ambulatory peritoneal
      dialysis (CAPD) as well as Continuous Cycler-Assisted Peritoneal Dialysis (CCPD)
      have additional advantages in patients with diabetes. PD therapy will be better
      tolerated than HD, the blood pressure is more stable and vascular access is not
      necessary. Preserving residual renal function (RRF) is of paramount importance to
      prolong the survival outcomes in PD patients. In insulin-dependent diabetic
      patients intraperitoneal insulin substitution can be used. The development of
      new, more biocompatible PD solutions holds promise for the future. Nevertheless,
      in many countries HD is further more favoured in the treatment of patients with
      ESRD.

PMID- 22971683
TI  - Kidney transplantation in emerging countries: do we know all issues?
AB  - Although it seems that end stage renal disease (ESRD) therapies gradually become
      more accessible in the developing world, yet, the vast majority of people living
      in those areas do not have access to dialysis and especially transplantation
      because of the economic and technological inequality as compared with the
      developed world. Despite the great advantage in survival and considerable
      socioeconomic advantages of transplantation vs. dialysis, there is a widespread
      recognition that the growing gap between organ supply and demand will continue
      into the foreseeable future. Several reasons might be considered in this regard
      as: insufficient data on the topic in the public domain, inadequate governmental
      financial resources, lack of public awareness, education and motivation for organ
      donation as well as the low number of organized teams of transplant surgeons and
      nephrologists, and lack of organizational infrastructure, i.e. coordinators. The
      defined priorities for the future in terms of improving living donor
      transplantation, composition of the official waiting lists and registries of
      transplant recipients and living donors and the role of transplant professionals
      have been discussed. In conclusion, whatever the governmental support is, as
      professionals, we should just reinforce our efforts to help our patients as best
      as we can in the current situation.

PMID- 22971684
TI  - Cardiac autonomic dysfunction in hemodialysis patients assessed by heart rate
      variability.
AB  - Sudden cardiac death (SCD) is a major problem in patients with end stage renal
      disease (ESRD) on haemodialysis (HD) and several risk factors are recognized. A
      major problem may be the autonomic dysfunction which is observed in more than 50
      % of ESRD patients. Autonomic dysfunction, and in particular cardiac autonomic
      dysfunction, is associated with a high risk of ventricular arrhythmias which may
      eventually lead to SCD. A non-invasive method for measuring cardiac autonomic
      function is by assessing heart rate variability (HRV) and this review will focus
      on HRV in HD patients. ESRD patients have an impaired HRV which may partly
      explain their high risk of SCD. Some intervention studies in HD patients using
      HRV as a surrogate parameter have been published and are also discussed in this
      review.

PMID- 22971685
TI  - Serum adiponectin and leptin levels are useful markers for prostate cancer
      screening after adjustments for age, obesity-related factors, and prostate
      volume.
AB  - AIM: Adiponectin and leptin, polypeptide hormones produced by adipocytes, have
      recently been reported to be associated with prostate cancer risk, though, the
      relationship remains poorly understood. We examined the association of
      adiponectin and leptin levels in serum with prostate cancer risk after
      adjustments for age, obesity-related factors, and prostate cancer risk. METHODS:
      Fifty-four prostate cancer patients and 70 control subjects provided blood
      sampled between 2008 and 2009. Using those, we determined serum adiponectin and
      leptin levels, and evaluated their relationships with prostate cancer risk after
      adjustments for age, obesity-related factors (body weight, body mass index, waist
      circumference), and prostate volume. Adipokine densities were calculated by
      dividing serum level with prostate volume. RESULTS: There were no differences for
      median serum adiponectin and leptin levels between the prostate cancer and benign
      control groups (P=0.22 and 0.78, respectively). Patients with levels of both
      adipokines in the highest quartile after adjustment for age had significantly
      higher risks of prostate cancer (adiponectin: odds ratio [OR] 2.79, P=0.014;
      leptin: OR 2.72, P=0.027). Patients with an adiponectin level greater than the
      median after adjustment for body weight also had a significantly elevated risk of
      prostate cancer (OR 2.22, P=0.031), whereas, those with a leptin level
      significantly greater than the median had a significantly lower risk (OR 0.46,
      P=0.027). Furthermore, median adiponectin density was significantly higher in the
      prostate cancer group than the benign group (P=0.0033). CONCLUSION: Serum
      adiponectin and leptin levels are useful markers for prostate cancer risk after
      adjustments for age, obesity-related factors, and prostate volume.

PMID- 22971686
TI  - Cholinergic drugs for treatment of recurrent urinary retention in high surgical
      risk/elderly BPH patients. A pilot study.
AB  - AIM: Urinary retention (UR) secondary to benign prostatic hyperplasia often leads
      patients to surgery, especially those who fail to urinate following a trial
      without catheter (TWOC). However, patients of high surgical risk and/or elderly
      patients with co-morbidities are usually not eligible for surgical treatment.
      Moreover, recurrent UR may indicate a poor detrusor function representing a risk
      factor of surgical therapy failure. Our objective was to evaluate the role of
      distigmine bromide, an anticholinesterase agent, to promote a successful TWOC in
      patients with recurrent UR. METHODS: Seventeen elderly and/or high surgical-risk
      patients with recurrent UR and prior failures to TWOCs received a combination of
      alpha-blocker along with distigmine bromide and have been retrospectively
      compared with that of 20 first-time UR patients who received only the alpha
      blocker just after emergency catheterization. The short-term outcome was measured
      by resumption of voiding, number of TWOC failures preceding successful voiding,
      determination of post-voiding residual volume (PVR), and International Prostate
      Symptom Score (IPSS). RESULTS: The majority of patients on combination therapy
      had a successful TWOC, similarly to all first-time urinary retention patients.
      Compared to patients on monotherapy, patients on combination therapy needed more
      TWOCs to void due to gradual increase in the dosage of distigmine bromide. PVR
      was significantly reduced with treatment in both groups. Statistically, there was
      no significant difference between the two groups on the PVR and IPSS mean change.
      CONCLUSION: Our results suggest that the combination of alpha-blocker and
      distigmine may eventually benefit patients with recurrent UR and prior
      unsuccessful TWOCs, to void.

PMID- 22971687
TI  - Serum carbohydrate antigen 19-9 levels in patients with unilateral hydronephrosis
      due to urinary lithiasis.
AB  - AIM: We aimed to investigate that the association between serum carbohydrate
      antigen 19-9 (CA 19-9) levels and unilateral hydronephrosis due to urinary
      lithiasis in homogeneous groups who had no urinary tract infection and renal
      impairment. METHODS: A total of 50 patients with ureteral stone enrolled in this
      study prospectively. The patients were divided into two groups according to
      degree of hydronephrosis. Patients without hydronephrosis were taken into Group I
      and who had hydronephrosis were taken into Group II. All patients were underwent
      treatment of shock wave lithotripsy (SWL). Serum CA 19-9 was measured using
      immunassay method pre-treatment of SWL. After complete stone clearence and
      recovery of hydronephrosis in all patients, patiens were re-evaluated and CA 19-9
      levels were measured. RESULTS: There were no significant differences for age,
      gender, body mass index, stone volume, shock wave number, number of SWL seasons,
      and serum creatinin between the groups (P>0.05). Pre-SWL serum mean Ca 19-9
      levels were 14.82+/-14.64 U/mL. in Group I and 13.89+/-13.03 U/mL. in Group II
      (P=0.8686). After complete stone clearance and recovery of hydronephosis with
      SWL, the mean CA 19-9 values were measured as 14.14+/-10.67 U/mL. in Group II and
      there were not found significant change as compared pre-SWL values for Group II
      (P=0.7334). CONCLUSION: The relationship between CA 19-9 values and
      hydronephrosis was not found to be statistically meaningful on the contrary to
      previous reports and it does not appear as a useful parameter to predict of
      urinary obstruction non-invasively.

PMID- 22971688
TI  - BK virus nephropathy and immunosuppression: the non-transplant setting.

PMID- 22971690
TI  - Non-emissive plastic colour filters for fluorescence detection.
AB  - We report the fabrication of non-emissive short- and long-pass filters on plastic
      for high sensitivity fluorescence detection. The filters were prepared by
      overnight immersion of titania-coated polyethylene terephthalate (PET) in an
      appropriate dye solution - xylene cyanol for short-pass filtering and fluorescein
      disodium salt for long-pass filtering - followed by repeated washing to remove
      excess dye. The interface between the titania and the dye molecule induces
      efficient quenching of photo-generated excitons in the dye molecule, reducing
      auto-fluorescence to negligible values and so overcoming the principal weakness
      of conventional colour filters. Using the filters in conjunction with a 505 nm
      cyan light-emitting diode and a Si photodiode, dose-response measurements were
      made for T8661 Transfluosphere beads in the concentration range 1 * 10(9) to 1 *
      10(5) beads MUL(-1), yielding a limit of detection of 3 * 10(4) beads MUL(-1).
      The LED/short-pass filter/T8661/long-pass filter/Si-photodiode combination
      reported here offers an attractive solution for sensitive, low cost fluorescence
      detection that is readily applicable to a wide range of bead-based
      immunodiagnostic assays.

PMID- 22971691
TI  - Control of framework interpenetration for in situ modified hydroxyl
      functionalised IRMOFs.
AB  - By intimate control of reaction conditions, phase-pure crystalline porous metal
      organic framework materials [Zn(4)O(L)(3)] with interpenetrated and non
      interpenetrated structures can be synthesised. Under certain conditions, these
      reactions occur with concomitant deprotection of masked alcohols located on the
      organic links which yield accessible 'metal-binding' functional groups within the
      frameworks.

PMID- 22971689
TI  - Interview as intervention: the case of young adult multidrug users in the club
      scene.
AB  - This paper reports on changes in substance use and substance dependence symptoms
      without intervention-among young adult multidrug users in the club scene, ages 18
      29, (N = 444) who participated in a natural history study. Computer-assisted
      personal interviews at baseline and 6-, 12-, and 18-month follow-ups included
      well-tested measures of substance use and dependence. Changes in substance
      dependence symptoms and drug use frequencies were calculated using Cohen's d
      statistic. Mean age was 22; 40% were female; 58% were Hispanic, 17% White, and
      21% Black. At 18-month follow-up assessment, participants reported significantly
      fewer days of cocaine (d = -.85 at 18 months), ecstasy (d = -.93), benzodiazepine
      (d = -.82), and prescription opioid (d = -.81) use, as well as reduced substance
      dependence symptoms (d = -.42). These results, together with data from focus
      groups with completers, suggest that comprehensive health and social risk
      assessments may have quite strong intervention effects among young adult
      multidrug users.

PMID- 22971693
TI  - Development of pyrrole-imidazole polyamide targeting fc receptor common gamma
      chain for the treatment of immune-complex related renal disease.
AB  - Fcgamma receptors I and III are thought to be involved in the development of
      lupus nephritis. Expression of Fc receptor common gamma chain (FcRgamma) is
      necessary for the stable expression of Fcgamma receptors I and III. The aim of
      this study was to develop a novel agent for the treatment of immune complex
      related renal disease using a gene regulator, pyrrole(Py)-imidazole(Im) (PI)
      polyamide, targeting the mouse FcRgamma gene promoter. Two PI polyamides
      targeting FcRgamma promoters were designed and synthesized. The effect of the PI
      polyamides on FcRgamma mRNA expression was evaluated in J774.A cells by real-time
      polymerase chain reaction (PCR), and CD16/32 protein expression was determined by
      immunocytochemical analysis and flow cytometry. The effects of these polyamides
      on FcRgamma gene expression and CD16/32 protein expression were evaluated in
      mouse peripheral blood mononuclear cells (PBMCs). One milligram per kilogram body
      weight of PI polyamide was injected via the tail vein every 2 d for 1 week and
      PBMCs were collected and analyzed. PI polyamide showed a specific binding to the
      target DNA in a gel mobility shift assay. Treatment of J774.A cells with 1.0 uM
      PI polyamide 1 significantly reduced FcRgamma mRNA expression and CD16/32 surface
      protein expression in J774.A cells. Similarly, PI polyamide significantly
      decreased expression of FcRgamma mRNA and CD16/32 in the PBMCs of C57B6 mice. PI
      polyamide designed to bind the FcRgamma promoter decreased FcRgamma gene and
      CD16/32 protein expression. PI polyamide targeting the FcRgamma gene may be a
      novel gene regulator for the prevention of lupus nephritis or other immune
      complex-related disease.

PMID- 22971694
TI  - Rapid sequencing of a peptide containing a single disulfide bond using high
      energy  collision-induced dissociation.
AB  - A peptide containing a single disulfide bond was sequenced using high-energy
      collision-induced dissociation (HE-CID) in conjunction with a high mass
      resolution time-of-flight  tandem mass spectrometer equipped with a matrix
      assisted laser desorption/ionization source. This mass spectrometer, which has
      spiral ion  trajectory, allowed both high mass resolution and high precursor ion
      selectivity. It is difficult to obtain sufficient product ions from peptides
      containing disulfide bonds using HE-CID due to the single collision in the gas
      phase. To compensate for insufficient dissociation, the disulfide bond was
      cleaved via an in-source reduction process using 1,5-diaminonaphthalene, a
      reducing matrix. After applying the reduction in the ionization, subsequent
      sequencing using HE-CID provided the detailed structural information of the
      peptide containing the single disulfide bond.

PMID- 22971695
TI  - A comparative study of homolytic reactions of fullerenes with aldehydes in a mass
      spectrometer under electron impact and in solution under UV irradiation.
AB  - C(60) was reacted in the ionization chamber of a mass spectrometer under electron
      impact (EI) with aldehydes, RCHO (R = Ph, p-FC(6)H(4), F(5)C(6), p-MeOC(6)H(4),
      alpha-thienyl, o-HOC(6)H(4), o-BrC(6)H(4), m-BrC(6)H(4) and t-Bu), with the
      transfer of R* radicals and with Me*-transfer from i-PrCHO and t-BuCHO.
      Paramagnetic fullerene derivatives were stabilized by the addition of the next R*
      radical or a hydrogen atom, or hydrogen or bromine atom loss. A detailed study
      showed that the reaction between C(60) and PhCHO occurred via a homolytic
      mechanism that matches one reported earlier for the reaction with acetone. This
      suggests the generality of the mechanism for the reactions of fullerenes with
      other species in ionization chambers under EI at ca 300 degrees C. All aldehydes,
      except one, had radicals at the carbonyl group which were different from those in
      the ketones examined earlier in the reactions. This expanded the variety of
      radicals which can be transferred to fullerenes during reactions in ionization
      chambers under EI. Due to this and the hydrogen atom at the CO group of
      aldehydes, some reactions occurred that were not found for the ketones: the
      formation of cyclic products C(60)COC(6)H(4) and C(60)OC(6)H(4) for PhCHO, o
      BrC(6)H(4)CHO and o-HOC(6)H(4)CHO, respectively, and HC(60)Ph for o- and m
      BrC(6)H(4)CHO. The reaction with alpha- formylthiophen gives the first example of
      transferring an aromatic heterocyclic radical to C(60) in an ionization chamber
      under EI. C(70) reacted with PhCHO, p-FC(6)H(4)CHO and i- PrCHO similarly to
      C(60). The results for the reactions of C(60) with PhCHO and with i- PrCHO were
      compared with those in solution under UV irradiation. Incomplete but reasonable
      coincidence was found; in both modes, the addition of Ph*, PhCO* and Me* radicals
      to C(60) occurred, whereas some other products were formed in solution, and the
      explanation is given as  to why this occurred. This conformity supports the
      hypothesis based on the results of kindred reactions with ketones and
      organomercurials: the results of EI-initiated homolytic reactions between
      fullerenes and other compounds in an ionization chamber can predict the
      reactivity of the fullerenes toward them in solution.

PMID- 22971696
TI  - Use of ESI-MS to determine reaction pathway for hydrogen sulphide scavenging with
      1,3,5-tri-(2-hydroxyethyl)-hexahydro-s-triazine.
AB  - To study the reaction between hydrogen sulphide and 1,3,5-tri-(2-hydroxyethyl)
      hexahydro-s-triazine, which is an often used hydrogen sulphide scavenger, electro
      spray ionisation mass spectrometry (ESI-MS) was used. The investigation was
      carried out in positive mode, and tandem mass spectrometry was used to
      investigate the nature of unknown peaks in the mass spectra. The reaction was
      found to proceed as expected from theory with the triazine reacting with hydrogen
      sulphide to form the corresponding thiadiazine. This species subsequently reacted
      with a second hydrogen sulphide molecule to form the dithiazine species, hereby
      confirming previously obtained results and showing the ability of the ESI-MS
      method for studying the scavenging reaction. The final theoretical product s
      trithiane was not detected. Furthermore, fragmentation products of thiadiazine
      and dithiazine were detected in the solution, and possible pathways and
      structures were  suggested to describe the observed fragments. In these,
      thiadiazine fragmented to 2-(methylidene amino)-ethanol and 2-(1,3-thiazetidin-3
      yl)-ethanol and N-(2-hydroxyethyl)-N-(sulfanylmethyl)-ethaniminium, which
      underwent a further fragmentation to N-methyl-N-(2-oxoethyl)-methaniminium.
      Dithiazine fragmented to N-methyl-N-(2-oxoethyl)-methaniminium as well. The by
      product from this reaction is methanedithiol, which was not detected due to its
      low polarity.

PMID- 22971697
TI  - Reactions of aminoguanidine with alpha-dicarbonyl compounds studied by
      electrospray ionization mass spectrometry.
AB  - Aminoguanidine possesses extensive pharmacological properties. This drug is
      recognized as a powerful alpha-dicarbonyl scavenger. In order to better elucidate
      the reactivity of aminoguanidine with alpha-dicarbonyls, aminoguanidine was
      reacted with several aldehydic and diketonic alpha-dicarbonyls. Electrospray
      ionization mass spectrometry is a suitable technique to study chemical and
      biochemical processes, and was selected for the purpose. In aminoguanidine
      reactions, triazines were detected and, other compounds that have never been
      reported before were identified. Triazine precursor forms were detected, namely
      tetrahydrotriazines and singly dehydrated tetrahydrotriazines. Moreover, species
      with bicyclic ring structures, and dehydrated forms, were also identified in
      aminoguanidine reactions. These species appear to result from tetrahydrotriazines
      and triazines reactions with one dicarbonyl molecule. Experiments revealed that
      these bicyclic species, in particular the ones resulting from triazines
      reactivity, could exist in solution, since they were both identified in the
      reactions of aminoguanidine and of a selected triazine with the dicarbonyls
      studied. The results obtained, regarding aminoguanidine/triazines reactivities,
      appear to support the capability of triazines to condensate and form polycyclic
      ring structures, and also to support literature mechanistic data for
      dihydroimidazotriazines formation via dihydroxyimidazolidine-triazines. The data
      obtained in this study may prove to be valuable to complement solution
      information, concerning the reactivity of amines with alpha-dicarbonyls, in
      particular.

PMID- 22971698
TI  - Design and performance of a desktop time-of-flight mass spectrometer for
      analyzing metal ions.
AB  - We have described a home-made desktop orthogonal-injection time-of-flight (O-ToF)
      mass spectrometer combining a collisional cooling system. This O-ToF consists of
      a simple electrospray ion source, an atmosphere-vacuum interface, an area of
      transmission, including a radio-frequency only quadrupole (RF- only quadrupole,
      RFQ) as a collisional cooling cell and an orthogonal ToF mass analyzer. In order
      to detect ions of small m/z value, such as small metal ions, the RFQ has been
      improved to weaken the mass discrimination effect against low mass ions. Metal
      salt solutions were used in the experiment. The system has shown a satisfactory
      resolving power in the spectra (m/Deltam = 3500), a good mass stability, a limit
      of detection of 80 fg and a mass accuracy of 48 ppm. The dynamic range is found
      to be from 10(-8) mol L(-1) to 10(-5) mol L(-1), allowing the semi-quantitative
      analysis of metal ions.

PMID- 22971699
TI  - Detection of peginesatide in equine serum using liquid chromatography-tandem mass
      spectrometry for doping control purposes.
AB  - Erythropoietin (EPO) and its recombinant analogues are suspected to be illicitly
      administered to horses for performance enhancing purposes and, consequently,
      prohibited in equine sports. Recently, a new erythropoiesis-stimulating agent,
      peginesatide (Omontys, formerly referred to as Hematide), belonging to the
      upcoming class of EPO-mimetic peptides, received approval for the treatment of
      anaemia in humans with chronic kidney disease on dialysis. As the pegylated
      dimeric peptide of approximately 45 kDa without sequence  homology to EPO is not
      detectable by conventional EPO detection assays, specific methods are bound to be
      established for horse sports drug testing. Thus, by fortifying equine serum with
      peginesatide, an approach consisting of a proteolytic digestion with subtilisin
      after protein precipitation was developed, eventually targeting a proteotypic and
      xenobiotic pentapeptide which is easily accessible to liquid chromatography-
      tandem mass spectrometry analysis. The method was validated for qualitative
      purposes and demonstrated to be  specific, precise (relative standard deviations
      below 14%), sensitive (limit of detection 10 ng mL(-1)) and linear. Being simple,
      cost-effective and readily transferable to other doping control laboratories, a
      mass spectrometric assay for the detection of therapeutic concentrations of
      peginesatide in equine serum is, in terms of preventive doping research,
      applicable to routine analysis shortly after approval of the drug.

PMID- 22971700
TI  - Characterization by electrospray ionization and tandem mass spectrometry of
      rhamnolipids produced by two Pseudomonas aeruginosa strains isolated from
      Brazilian crude oil.
AB  - In this work, biosurfactants produced by two Pseudomonas aeruginosa strains
      isolated from Brazilian crude oils were identified by proton nuclear magnetic
      resonance ((1)H NMR) and further characterized by mass spectrometry (MS) coupled
      with electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) analysis
      in positive mode and their surface activities evaluated. Mono-rhamnolipids and di
      rhamnolipids were identified for both isolates, but the most abundant were found
      to be mono-rhamnolipids. The similarity of rhamnolipids produced by the two
      strains was in good agreement with their surface activities. Both biosurfactants
      exhibited similar aqueous solution surface tensions, high emulsification indexes
      and critical  micelle concentration values. The results obtained show that ESI-MS
      and MS/MS analysis alone provide a fast  and highly specific characterization of
      biosurfactants produced by microbial strains.

PMID- 22971701
TI  - Hepatoblastoma metastasis confined to the pulmonary artery: report of a case.
AB  - Here, we report a case of hepatoblastoma metastasis to the left pulmonary artery
      which was resected by left lingular segmentectomy plus left lower lobectomy in 5
      year-old girl. She had previously undertaken right upper lobectomy and multiple
      lung partial resections on bilateral lungs as hepatoblastoma metastatectomies.
      Prediction of postoperative pulmonary function based on perfusion scan merged
      with CT image and the measurement by CT volumetry, showed that left lingular
      segmentectomy plus left lower lobectomy could preserve 78% of the preoperative
      functional values and resection was done. Three weeks after the operation, her
      condition recovered to the preoperative level. Pathological examination showed
      that the metastasis was tumor embolism of hepatoblastoma which extended into the
      pulmonary arterial wall, which to our knowledge, has not been previously
      reported.

PMID- 22971702
TI  - Left atrial papillary fibroelastoma accidentally diagnosed with gastric cancer.
AB  - Papillary fibroelastoma is a rare but benign cardiac tumor and usually originates
      from the cardiac valve. We describe a 78-year-old woman who was initially
      diagnosed with gastric cancer, and was incidentally found to have a mass in the
      free wall of her left atrium between the left atrial appendage and the left
      superior pulmonary vein. An excision was performed through the left atrial
      appendage under cardiopulmonary bypass. The histopathologic examination of the
      resected tissue revealed a papillary fibroelastoma. The unusual localization of
      this papillary fibroelastoma was discussed.

PMID- 22971703
TI  - Spontaneous rupture of internal iliac artery secondary to anticoagulant therapy.
AB  - We present a case of spontaneous retroperitoneal hemorrhage secondary to
      anticoagulant therapy. A 41-year-old woman who underwent aortic valve replacement
      due to infective endocarditis 2 months ago was admitted for evaluation of
      dizziness and fatigue. Physical examination revealed the abdomen to be distended.
      Blood work showed a hemoglobin 4.5 and INR 3.5. Abdominal CT showed a huge intra
      abdominal hematoma with right internal iliac artery rupture. In abdominal aortic
      angiography, rupture of right internal iliac artery was confirmed and treated
      with embolization. Bleeding stopped after embolization, but she developed acute
      renal failure secondary to a huge hematoma. On POD#4, she underwent a laparotomy
      and the hematoma was evacuated. The patient had an uneventful recovery and was
      discharged from the hospital with no further bleeding episodes.

PMID- 22971704
TI  - Aortic bleeding one week after removal of an intraoperative epicardial temporary
      pacing wire.
AB  - A 56-year-old man had left nephrectomy and resection of a cavoatrial tumor
      thrombus under a cardiopulmonary bypass assist for left renal cell carcinoma. An
      intraoperative bipolar temporary epicardial atrial pacing wire was removed on
      postoperative day 8. The patient collapsed on postoperative day 15. Emergent
      transthoracic echocardiography and computed tomography scanning with contrast
      media detected cardiac tamponade. The three-dimensional volume-rendering images
      from the multislice computed tomography scan demonstrated bleeding from the
      aortic root. Upon emergency operation, active arterial bleeding from the aortic
      root distal to the sites of cannulation and cardioplegia was confirmed, and
      hemostasis with sutures was completed. It is well known that the intraoperative
      temporary epicardial pacing wire can cause bleeding or arrhythmia, especially
      when the wire is being removed. However, bleeding usually occurs from the
      inserted epicardial point of the pacing wire soon after removal of the wire. To
      our knowledge, this late bleeding complication of the pacing wire is a previously
      unreported serious iatrogenic complication after cardiac surgery.

PMID- 22971705
TI  - A case of solitary pulmonary nodular amyloidosis with Sjogren's syndrome.
AB  - Patients with Sjogren's syndrome frequently have pulmonary involvement, but the
      involvement of nodular pulmonary lesions, including pulmonary amyloidosis, is
      rare. Most cases of pulmonary amyloidosis involve multiple nodules; solitary
      pulmonary nodular amyloidosis, as an associated condition of Sjogren's syndrome,
      is very rare.In our report, we present the case of an 80-year-old female with
      Sjogren's syndrome who was incidentally found to have a small solitary pulmonary
      nodule. The nodule showed high fluorodeoxyglucose uptake and contained areas of
      calcification. Because the probability that the nodular lesion was malignant
      could not be excluded, the tumor was excised using a thoracoscopic procedure; the
      final diagnosis was pulmonary nodular amyloidosis. Although most cases of
      pulmonary amyloidosis involve multiple nodules, amyloidosis should be considered
      in the differential diagnosis for a solitary pulmonary nodule in patients with
      Sjogren's syndrome.

PMID- 22971706
TI  - Thoracoscopic plication for diaphragmatic eventration in a neonate.
AB  - BACKGROUND: Currently, thoracoscopic surgery is replacing thoracotomy for an ever
      increasing number of indications, even in pediatric surgery. However, there are
      few reports describing thoracoscopic plication (TP) for diaphragmatic eventration
      in children, particularly in neonates. We report a case of TP under single-lung
      ventilation in a neonate with diaphragmatic eventration. CASE REPORT: A 10-day
      old boy was referred for surgical management of right diaphragmatic eventration.
      Birth was at term, following an uncomplicated pregnancy and delivery. Shortness
      of breath, labored respiration and chest retraction presented soon after birth,
      necessitating mechanical ventilation. Chest radiography and computed tomography
      revealed an elevated right hemidiaphragm. Attempted weaning off mechanical
      ventilation failed with persistence of respiratory symptoms, requiring nasal
      directional positive airway pressure. However, because there was no resolution of
      symptoms, TP was performed using a 3 port technique under single-lung ventilation
      on day 17 of life. The postoperative course was excellent with complete
      resolution of respiratory symptoms with no recurrence for 9 months. CONCLUSION:
      To the best of our knowledge, this is the youngest case of TP for diaphragmatic
      eventration performed under single-lung ventilation. TP is safe, effective and
      minimally invasive and should be considered actively for the treatment of
      symptomatic diaphragmatic eventration even in neonates.

PMID- 22971707
TI  - Recurrent aortic aneurysm due to Behcet's disease: a case report from China.
AB  - In this report, we present a twenty-nine year old patient with a five-year
      history of Behcet's disease (BD), who developed an ascending aortic aneurysm.
      Chest enhanced computed tomography scanning demonstrated a saccular aneurysm of
      the ascending aorta, with a maximum diameter of 11 cm. The patient was
      administered with prednisone, thalidomide and anticoagulant. A regular follow up
      was carried out. The patient lived well with blood sedimentation and C-reactive
      protein in the normal range.

PMID- 22971708
TI  - Eight-year follow-up of a high-risk patient treated for Crawford Type II
      thoracoabdominal aortic aneurysm (TAAA) with a multistage hybrid open
      endovascular repair.
AB  - The case of a patient with type II TAAA (thoracoabdominal aortic aneurysm), who
      underwent multistage hybrid procedure, is presented. This high-risk patient was
      excluded as ineligible for conventional open repair. At first, the bypass between
      both common carotid arteries was inserted. Then, the transperitoneal viscerorenal
      revascularization was performed to ensure blood perfusion. At the end, the stent
      graft from the aorta arch to its bifurcation was deployed with endovascular
      techniques. This stent graft covered left common carotid artery, left subclavian
      artery, visceral trunk, superior mesenteric artery and both renal arteries. The
      patient had been observed for eight years with relatively low complication rate.
      The hybrid open-endovascular repair (HOER) shows promising results in patients at
      prohibitive risk for classic reconstruction.

PMID- 22971709
TI  - Chondromyxoid fibroma with secondary aneurysmal bone cyst of the rib.
AB  - Chondromyxoid fibroma (CMF) is a rare, benign cartilaginous tumor, comprising
      less than 1% of primary bone tumors, and usually occurs in the metaphysis of a
      long tubular bone around the knee. We report a rare case of CMF of the rib. The
      patient was a 25-year-old man who visited the hospital for left upper back pain.
      Roentgenography revealed an 8-cm mass in the left upper lung field; computed
      tomography revealed a large multicystic tumor with aneurysmal bone cyst (ABC)
      like features in the posterior mediastinum. ABCs are also a rare benign tumor
      representing 2.5% of primary bone tumors, and most of ABCs are located in the
      metaphysis of long bones and vertebrae. To the best of my knowledge, there is no
      report of CMF with secondary ABC of the rib. We performed total resection of the
      tumor. Complete tumor resection may be the best treatment option for a cure.

PMID- 22971710
TI  - Complete laceration of the middle lobe bronchus caused by blunt trauma.
AB  - Bronchial ruptures due to blunt trauma are rarely encountered injuries. A
      previously healthy 42-year-old man fell from heights of 8 meters. A prompt chest
      tube-drainage for suspected right sided tension pneumothorax and a tracheal
      intubation were performed. Massive air leak and pneumothorax of the right lung
      continued. Laceration of the tracheobronchial tree was suspected. Operation was
      performed 20 hours after patient's arrival. The complete avulsion of the middle
      lobe bronchus was identified during operation, and a middle lobectomy was
      performed. The patient was transferred to a rehabilitation hospital on 20th post
      operative day without complication. Early decision making for surgery resulted in
      a good outcome. When a complete atelectasis of the whole right lung and a massive
      air leakage continues despite appropriate chest-tube drainage in a blunt trauma
      patient, laceration of the tracheobronchial tree should be suspected.

PMID- 22971711
TI  - Valve-sparing replacement of the aortic root after repair of tetralogy of Fallot.
AB  - Progressive aortic root dilatation is a common feature after surgical repair of
      tetralogy of Fallot. This report describes a successful valve-sparing replacement
      of the aortic root in a patient with significant dilated aortic root and aortic
      regurgitation after repair of tetralogy of Fallot.

PMID- 22971712
TI  - Multiregional embolizations and Takotsubo cardiomyopathy associated with left
      atrial myxoma.
AB  - Cardiac myxoma represents the most common primary cardiac neoplasm, accounting
      for nearly 75% of benign cardiac tumor. Tumor embolisms occur in 30% to 40% of
      patients with myxoma, and half of these are cerebral arteries. To our knowledge,
      this is the first published report of multiregional tumor embolizations except
      for cerebral artery and Takotsubo cardiomyopathy in patients with left atrial
      myxoma.

PMID- 22971713
TI  - Effective utilization of chest X-ray for follow-up of metastatic lung tumor due
      to soft tissue sarcoma.
AB  - Computed tomography (CT) is widely used for follow-up of lung metastasis in
      patients due to soft tissue sarcoma (STS), the frequency of chest X-ray (CXR) is
      obviously reduced. This study verified the current status of diagnostic measures
      and the efficacy of CXR. A retrospective analysis of 18 patients that underwent
      surgery for lung metastasis due to STS was performed. The investigation compared
      the follow-up interval using CT after STS surgery, time from STS surgery to lung
      metastasis, tumor size of lung metastasis, detection rate with CXR, time from
      detection to surgery for lung metastasis, number of CT scans and follow-up
      interval using CT after detection of lung metastasis. The follow-up interval when
      using CT after STS surgery was 3.5 months (m). Time from STS surgery to lung
      metastasis was 34.3m. Tumor size of lung metastasis was 15 mm, and the detection
      rate by CXR was 66.7%. The time from detection to surgery for lung metastasis was
      4.8m, the number of CT scans was 3.1, and the interval was markedly shortened to
      1.6m. Follow-up should be performed by CXR if the tumor is detected by CXR. CT
      evaluation is required when the tumor size has increased, and prior to surgery
      for lung metastasis.

PMID- 22971714
TI  - Inhibition of TNF-alpha by cyclophosphamide reduces myocardial injury after
      ischemia-reperfusion.
AB  - PURPOSE: The purpose of this study was to determine whether cyclophosphamide (CP)
      can decrease myocardial and systemic TNF-alpha expression and thus protects
      myocardial I/R injury. METHODS: Open chest rats were subjected to 30 min of
      ischemia followed by 3h, 12h or 24h of reperfusion. Rats were divided into sham
      group, I/R group and CP group, and each group included 3 timepoint subgroups (3h,
      12h and 24h). Plasma TNF-alpha was measured by cytometric bead array (CBA) and
      immunohistochemistry was used to detect TNF-alpha in myocardium. RESULTS:
      Compared with I/R group, rats treated with CP showed a significant difference
      with decreased plasma TNF-alpha (13.31 +/- 2.62 vs 14.13 +/- 5.95 pg/mL at 3 h
      reperfusion, 10.1 +/- 2.73 vs 12.54 +/- 5.00 pg/mL at 12 h reperfusion, 10.38 +/-
      5.59 vs 13.00 +/- 3.59 pg/mL at 24 h reperfusion, p <0.05 respectively).
      Immunostaining was less intense with CP injection at each reperfusion time. The
      score of the intensity of myocardial TNF-alpha staining was down regulated.
      CONCLUSIONS: TNF-alpha is expressed in the myocardium and plasma after myocardial
      I/R injury. CP might be a feasible strategy for anti-TNF-alpha to protect
      myocardial I/R injury.

PMID- 22971715
TI  - Long-term results of modified Bentall procedure using flanged composite aortic
      prosthesis.
AB  - PURPOSE: We have been using the flanged composite aortic prosthesis and Carrel
      button technique to re-attach the coronary ostia in aortic root replacement
      procedures at our institution over the last twenty five years. Our objective was
      to evaluate the long-term results of aortic root replacement with this technique.
      METHODS: A total of 73 patients from January 1984 to August 2010 were included in
      this study. The median age was 52.7 +/- 14.4 years (range 28-80 years). There
      were 48 male and 25 female patients. 44 patients (60.3%) had annuloaortic
      ectasia, and 15 patients (20.5%) had acute type A aortic dissection. Marfan
      syndrome was recognized in 12 patients (16.5%). RESULTS: The early mortality rate
      was 5.5% (n = 4). Causes of death were multiple organ failures in two patients
      and sepsis in another two patients. The actuarial survival rate was 84.2% at 5
      years, 64.3% at 15 years and 51.9% at 25 years. Only one patient with aortitis
      needed a reoperation because of coronary pseudoaneurysm after 23 years from the
      previous operation. CONCLUSION: This modified Bentall procedure is reliable and
      safe, with superior long-term survival and a low rate of aortic reoperation.

PMID- 22971716
TI  - Perfect and least invasive sealing technique on the lesser curvature of the
      aortic arch: application of a novel stent graft to an aneurysm developing on a
      postoperative ductus arteriosus.
AB  - A 78-year-old woman who underwent an operation for a patent ductus arteriosus
      (PDA) about thirty years ago developed an aneurysm on the aortic side of the
      remnant ductal tissue. To avoid risky, open surgery, we performed endovascular
      aortic therapy using a novel stent graft (SG), which was pre-curved, fenestrated
      and custom-made type. This graft was designed to configure to the patient's whole
      aortic arch anatomy, and was capable of accurately adjusting its fenestrations to
      the arch branch orifices during the procedure. The operation was successful, and
      the patient was discharged uneventfully on 16th postoperative day. The advantage
      of this fenestrated SG is close sealing, especially over the lesser curvature of
      the arch. This device could be a simple and effective option to deal with an
      otherwise normal aortic arch with such a ductus-related localized lesion.

PMID- 22971717
TI  - Surgical results of video-assisted thoracic surgery and risk factors for
      prolonged hospitalization for secondary pneumothorax in elderly patients.
AB  - BACKGROUND: The treatment of secondary pneumothorax in elderly patients is
      difficult because of underlying diffuse lung injury and complex medical
      comorbidities. Such patients still have high morbidity rates, resulting in longer
      periods of hospitalization. METHODS: To examine the results of video-assisted
      thoracic surgery for elderly patients (aged 70 years or over) with secondary
      pneumothorax and investigate the risk factors for hospital stay longer than 7
      days, we retrospectively analyzed the results obtained in such patients at our
      institution. RESULTS: From among 73 patients who entered this study, 7 patients
      (9.6%) had postoperative complications. Video-assisted thoracic surgery could
      treat pneumothorax in 71 patients, except for the 2 who died in hospital. The
      median postoperative drainage and hospital stay periods were 2 days (1-40 days)
      and 5 days (2-51 days). Patients with interstitial pneumonitis, pulmonary
      infection and low total protein or sodium levels were the risk factors for
      hospital stay longer than 7 days. CONCLUSIONS: VATS is a safe and effective
      procedure for secondary pneumothorax in elderly patients. Patients with
      interstitial pneumonitis, pulmonary infection, and hyponutrition state were the
      risk factors for postoperative hospital stay prolongation.

PMID- 22971718
TI  - Endovascular aortic repair as second-stage surgery after hybrid open arch repair
      by the frozen elephant trunk technique for extended thoracic aneurysm.
AB  - PURPOSE: To retrospectively evaluate endovascular aortic repair after hybrid open
      arch repair using the frozen elephant trunk technique for extended thoracic
      aneurysm. METHODS: Thoracic endovascular aortic repair was performed in 10 of 227
      patients (4.4%) who had previously undergone treatment by use of the frozen
      elephant trunk technique. Six patients had extended thoracic aorta, and 4,
      complicated aortic dissection. Surgery was scheduled at an early stage in 5
      patients; the remaining 5 underwent repair for a new lesion that had developed
      during the chronic period. The interval between 2 stages was 0 to 86 months
      (mean, 24 months). The distal landing zone was at the level of thoracic vertebra
      10 level in 2 patients; 11, in 4; 12, in 2; and lumbar vertebra 1, in 2. All
      patients underwent preoperative cerebrospinal fluid drainage. RESULTS: None of
      the patients died, nor did any have spinal cord injuries. An Endoleak of the
      stent graft with shrinkage of aneurysm was not observed. The mean follow-up
      period was 18 months (range, 5-53 months). No deaths or aortic events occurred
      after the second-stage operation. CONCLUSIONS: The frozen elephant trunk
      technique reduced the incidence of second-stage thoracic endovascular aortic
      repair for extended thoracic aorta and also made the procedure easy and safe.

PMID- 22971719
TI  - Does warfarin help prevent ischemic stroke in patients presenting with post
      coronary bypass paroxysmal atrial fibrillation?
AB  - PURPOSE: This study examines the efficacy of warfarin in preventing ischemic
      stroke due to paroxysmal atrial fibrillation (PAF) after coronary artery bypass
      grafting (CABG). METHODS: Postoperative PAF occurred in 151(33.5%) of 447
      patients undergoing conventional CABG. The patients were divided into two groups:
      group I consisting of 93 patients administered two types of antiplatelet agents
      and group II consisting of 58 patients treated with a single antiplatelet agent
      and warfarin. We compared the two groups in terms of CHADS2 score, incidence of
      ischemic stroke, and independent risk for stroke associated with post-CABG PAF.
      RESULTS: The group I CHADS2 score (2.24 +/-1.67) was significantly lower than the
      group II score (2.64 +/- 1.22), p = 0.0452. However, 12 patients in group I
      (12.9%) suffered postoperative ischemic stroke, a rate significantly higher than
      that of group II (1 patient, 1.7%; p = 0.0173). Any recurrence of PAF or atrial
      fibrillation with bradycardia was assessed at the time of stroke onset. Logistic
      regression analysis showed that the absence of warfarin therapy constituted a
      risk factor for post-CABG stroke associated with PAF (Odds 13.04, p = 0.027).
      CONCLUSION: Warfarin therapy administered concomitantly with an antiplatelet
      agent dramatically reduced the incidence of ischemic stroke associated with
      postoperative PAF.

PMID- 22971720
TI  - Influence of weather conditions on the onset of primary spontaneous pneumothorax:
      positive association with decreased atmospheric pressure.
AB  - PURPOSE: Primary spontaneous pneumothorax is believed to result from blebs, or
      from other abnormalities of the pleural surface. There is no consensus as to
      whether a change in weather conditions can precipitate spontaneous pneumothorax.
      The aim of the present study was to investigate the influence of weather
      conditions on the onset of primary spontaneous pneumothorax. METHODS: The case
      histories of 1051 inpatients with primary spontaneous pneumothorax treated at
      Nissan Tamagawa Hospital between January 2006 and December 2011 were analyzed
      retrospectively. Data on weather conditions were collected daily throughout the 6
      year period. The data were analyzed to determine differences in weather
      conditions between days on which primary spontaneous pneumothorax occurred and
      those on which it did not. RESULTS: Primary spontaneous pneumothorax occurred on
      819 (37.3%) of 2191 study days. On days before and the day of primary spontaneous
      pneumothorax onset, the difference in mean atmospheric pressure was 0.6 hPa lower
      than on days in which no primary spontaneous pneumothorax occurred. This
      difference was statistically significant (P = 0.015). There was no statistical
      difference in mean, maximum, and minimum temperature, hours of sunshine, amount
      of precipitation, and mean and minimum humidity between days with and those
      without primary spontaneous pneumothorax. CONCLUSION: This largest study of the
      literature showed decreased atmospheric pressure might play an important role in
      the occurrence of primary spontaneous pneumothorax.

PMID- 22971721
TI  - A canine model of proximal descending thoracic aortic aneurysm created with an
      autologous pericardial patch.
AB  - OBJECTIVES: To establish an animal model of proximal descending thoracic aortic
      aneurysm for the study of branched stent grafts. MATERIALS AND METHODS: Eleven
      mongrel dogs underwent the surgical procedure during which an autologous
      pericardial patch was sewn onto a longitudinal incision in the anterolateral wall
      of the thoracic aorta near the left subclavian artery to create an artificial
      thoracic aortic aneurysm. RESULTS: All eleven animals survived the surgical
      procedure. One animal died from rupture at the surgical site during the first
      week after surgery. The distance between the artificial aneurysm and the left
      subclavian artery was 8.29 +/- 0.91 mm. The average diameter of the artificial
      aneurysms did not significantly change over the 4-month follow-up period.
      CONCLUSION: A canine model for proximal descending thoracic aortic aneurysm can
      be achieved using a safe and convenient method. The model can be used in the
      study of new branched stent graft applied to the aortic arch.

PMID- 22971722
TI  - Comparison of glucose fluctuations between day- and night-time measured using a
      continuous glucose monitoring system in diabetic dogs.
AB  - Monitoring of blood glucose concentration is important to evaluate the diabetic
      status of dogs. Continuous glucose monitoring systems (CGMS) have been applied in
      veterinary medicine for glucose monitoring in diabetic dogs. The purpose of the
      study was to evaluate the daily glycemic profiles obtained with CGMS and compare
      glucose fluctuations between day- and night-time in diabetic dogs. Five diabetic
      dogs were used in this study and were treated with either NPH insulin or insulin
      detemir. For data analyses, day-time was defined as 9:00 am-9:00 pm and night
      time as 9:00 pm-9:00 am. Using glucose profiles, we determined the mean glucose
      concentrations (1- and 12-hr intervals), and times spent in hyperglycemia >200
      mg/dl or hypoglycemia <60 mg/dl. None of the parameters differed significantly
      between day-time and night-time in dogs treated with NPH insulin or insulin
      detemir. In conclusion, this study confirmed, using CGMS, that there are no
      differences in glucose fluctuations between day- and night-time, in diabetic dogs
      on a similar feeding regimen and insulin administration.

PMID- 22971723
TI  - Minimal erythema dose (MED) in normal canine skin by irradiation of narrow-band
      ultraviolet B (NB-UVB).
AB  - Narrow-band UVB (NB-UVB) is light over a very narrow band of wavelengths (around
      311 nm) that is concentrated in the therapeutic range and minimally in the
      sunburn range. It has therefore become the phototherapy treatment of choice for
      skin diseases. The minimal erythema dose (MED) on canine skin for standardizing
      dosage schedules in NB-UVB treatment and histopathological analyses were
      performed in these dogs. In all 32 dogs tested, the MED ranged from 432 to 864
      mJ/cm(2). There were no significant differences in MED among breeds, sex and age
      groups. Histopathology obtained from areas irradiated by MED showed only mild
      vascular dilatation. These findings might be valuable for the application of NB
      UVB phototherapy to canine skin diseases.

PMID- 22971724
TI  - Different responses of selected hormones to three types of exercise in young men.
AB  - Exercise is a potent stimulus for release of growth hormone (GH), cortisol,
      testosterone and prolactin, and prolonged exercise inhibits insulin secretion.
      These responses seem to be specific to the type of exercise but this has been
      poorly characterised primarily because they have not been compared during
      exercise performed by the same individuals. We investigated hormone responses to
      resistance, sprint and endurance exercise in young men using a repeated measures
      design in which each subject served as their own control. Eight healthy non-obese
      young adults (18-25 years) were studied on four occasions in random order: 30-s
      cycle ergometer sprint (Sprint), 30-min resistance exercise bout (Resistance), 30
      min cycle at 70 % VO(2max) (Endurance), and seated rest in the laboratory (Rest).
      Cortisol, GH, testosterone, prolactin, insulin and glucose concentrations were
      measured for 60 min after the four different interventions. Endurance and sprint
      exercise significantly increased GH, cortisol, prolactin and testosterone. Sprint
      exercise also increased insulin concentrations, whereas this decreased in
      response to endurance exercise. Resistance exercise significantly increased only
      testosterone and glucose. Sprint exercise elicited the largest response per unit
      of work, but the smallest response relative to mean work rate in all hormones. In
      conclusion, the nature and magnitude of the hormone response were influenced by
      exercise type, perhaps reflecting the roles of these hormones in regulating
      metabolism during and after resistance, sprint and endurance exercise.

PMID- 22971725
TI  - Aortic distensibility is reduced during intense lower body negative pressure and
      is related to low frequency power of systolic blood pressure.
AB  - As sympathetic activity approximately doubles during intense lower body negative
      pressure (LBNP) of -60 mmHg or greater, we examined the relationship between
      surrogate markers of sympathetic activation and central arterial distensibility
      during severe LBNP. Eight participants were exposed to progressive 8-min stages
      of LBNP of increasing intensity (-20, -40, -60, and -80 mmHg), while recording
      carotid-femoral pulse wave velocity (cPWV), stroke volume (SV), heart rate, and
      beat-by-beat blood pressure. The spectral power of low frequency oscillations in
      SBP (SBP(LF)) was used as a surrogate indicator of sympathetically modulated
      vasomotor modulation. Total arterial compliance (C) was calculated as C =
      SV/pulse pressure. Both cPWV and C were compared between baseline, 50 % of the
      maximally tolerated LBNP stage (LBNP(50)), and the maximum fully tolerated stage
      of LBNP (LBNP(max)). No change in mean arterial pressure (MAP) occurred over
      LBNP. An increase in cPWV (6.5 +/- 2.2; 7.2 +/- 1.4; 9.0 +/- 2.5 m/s; P = 0.004)
      occurred during LBNP(max). Over progressive LBNP, SBP(LF) increased (8.5 +/- 4.6;
      9.3 +/- 5.8; 16.1 +/- 12.9 mmHg(2); P = 0.04) and C decreased significantly (18.3
      +/- 6.8; 14.3 +/- 4.1; 11.6 +/- 4.8 ml/mmHg * 10; P = 0.03). The mean correlation
      (r) between cPWV and SBP(LF) was 0.9 +/- 0.03 (95 % CI 0.79-0.99). Severe LBNP
      increased central stiffness and reduced total arterial compliance. It appears
      that increased sympathetic vasomotor tone during LBNP is associated with reduced
      aortic distensibility in the absence of changes in MAP.

PMID- 22971726
TI  - Enforced effect of tk-MCP-1 fusion gene in ovarian cancer.
AB  - OBJECTIVE: The efficiency of HSV-tk/GCV system is not high because of
      insufficient gene transfer and incompletely initiative of host antineoplastic
      potency. The present study was designed to assess the antitumor efficacy of tk
      MCP-1 on ovarian cancer in vitro and vivo. METHODS: A novel bicistronic
      expression system can help to improve the expression level of a gene in a stable
      manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a
      pLXSN retroviral vector and an internal ribosome entry site sequence by
      restriction enzyme. Western blot was performed to determine tk and MCP-1
      expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of
      SKOV3/tk-MCP-1 with or without monocytes were compared to those of SKOV3
      expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in
      SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in
      conjunction with suicide gene. RESULTS: The significant GCV-sensitively
      tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of
      pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The
      growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly
      suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor
      effect was associated with the recruitment of monocytes. CONCLUSION: These
      results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on
      ovarian cancer by orchestration of immune responses.

PMID- 22971727
TI  - Huntington disease-like 2 (HDL2) in Venezuela: frequency and ethnic origin.
AB  - Huntington disease (HD) phenotypes without a HTT mutation are known as HD-like
      (HDL) syndromes and are caused by mutations in other loci. HDL2, almost
      indistinguishable from HD, is due to expansions in the Junctophilin 3 locus
      (JPH3) with a worldwide Sub-Saharan ethnic origin. Sixteen independent patients
      with involuntary movements, psychiatric disturbances and ataxia not having a HTT
      mutation were searched for loci PRNP (prion protein, HDL1), JPH3 (HDL2), ATN1
      (dentatorubral-pallidoluysian atrophy), ATX2 (spinocerebellar ataxia 2) ATXN3
      (spinocerebellar ataxia 3), and TBP (spinocerebellar ataxia 17=HDL4). Markers
      Duffy, Kell, Diego, D9S1120, plus six JPH3 intragenic single-nucleotide
      polymorphisms were tested to ascertain ethnic origin. Four unrelated choreic
      patients had an expanded allele at JPH3. Three of them carried the African marker
      Duffy null. All four families carried with the mutation the same haplotype most
      frequent in African populations; Amerindian alleles D9D1120*9 and Diego A; or
      Kell allele K were absent. HDL2 in Venezuela had a low, but higher relative
      frequency (2.6%) than that in other Caucasoid populations. It should be searched
      first in choreic patients not having HTT mutations. The most likely remote ethnic
      origin for all detected families was African.

PMID- 22971728
TI  - Associations of variations in the MRF2/ARID5B gene with susceptibility to type 2
      diabetes in the Japanese population.
AB  - Modulator recognition factor-2 (Mrf2/AT-rich interaction domain (Arid)5b) has
      been revealed to be involved in pathogenesis of atherosclerosis and adipogenesis.
      Single-nucleotide polymorphisms (SNPs) in the MRF2/ARID5B gene are associated
      with coronary artery disease (CAD) and has been proposed as a candidate gene for
      type 2 diabetes (T2D). The study was aimed to determine whether any of the four
      MRF2/ARID5B SNPs (rs2893880, rs10740055, rs7087507 and rs10761600) associated
      with susceptibility to CAD are also associated with T2D, and to determine whether
      SNP genotype influences the levels of adiponectin and other clinical factors.
      Association of MRF2/ARID5B SNPs was investigated in 500 diabetic patients from
      the Department of Metabolic Diseases at the University of Tokyo and 243 hospital
      based nondiabetic individuals from the Institute for Adult Disease Asahi Life
      Foundation Hospital and 500 community-based nondiabetic individuals from the
      Hiroshima Atomic Bomb Casualty Council Health Management Center. Associations of
      haplotypes of these SNP with levels of adiponectin and other clinical factors
      were evaluated when the data was available. We found rs2893880C, rs10740055A,
      rs7087507A and rs10761600T were increasingly associated with T2D in terms of
      allele/genotype frequencies of each SNP and their haplotype combinations.
      Individuals with haplotype CAAT indicated an 1.86 times higher prevalence of
      diabetes compared with individuals with GCGA (OR 1.86 (95% confidence interval
      (CI) 1.43-2.41)). Furthermore, CAAT significantly associated with adiponectin
      levels and other clinical factors. In conclusion, polymorphisms on the
      MRF2/ARID5B gene were associated with susceptibility to T2D as well as
      adiponectin and other clinical factors, which was in a completely concordant way
      with their associations with CAD.

PMID- 22971729
TI  - Extended screening for major mitochondrial DNA point mutations in patients with
      hereditary hearing loss.
AB  - Hearing loss (HL) is the most common sensory disorder in humans. Many patients
      with mitochondrial diseases have sensorineural HL (SNHL). The HL of these
      patients manifests as a consequence of either syndromic or nonsyndromic
      mitochondrial diseases. Furthermore, the phenotypes vary among patients even if
      they are carrying the same mutation. Therefore, these features make it necessary
      to analyze every presumed mutation in patients with hereditary HL, but the
      extensive analysis of various mutations is laborious. We analyzed 373 patients
      with suspected hereditary HL by using an extended suspension-array screening
      system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other
      mtDNA mutations in addition to the previously analyzed 29 mutations. In the
      present study, we detected 2 different mtDNA mutations among these 373 patients;
      m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient
      (0.3%) for each. As these two patients had no clinical features other than HL,
      they had not been suspected of having mtDNA mutations. This extended screening
      system together with the previous one is useful for the genetic diagnosis and
      epidemiological study of both syndromic and nonsyndromic HL.

PMID- 22971732
TI  - An anatomic investigation of the elbow joint, with special reference to aging of
      the articular cartilage.
AB  - The architecture of the articular surface of the elbow joint and the location of
      cartilage degeneration with aging was analyzed. The study included 131 elbow
      joints of 66 cadavers preserved by embalming. The age of subjects at death ranged
      from 49 to 96 years (mean 79 years). The elbow joint was observed macroscopically
      and analyzed. The degenerative changes in the radiohumeral joint were always more
      advanced than those in the humeroulnar joint. The erosion or chondral defect in
      the capitulum is located in the area 45 degrees  anterior to the long axis of the
      humerus. The anterior part of the erosion in the crest separating the trochlea
      from the capitulum was roughly 48.5 degrees  to the long axis of the humerus. It
      was similar in position to the erosion found in the capitulum. Based on the
      degree and area of cartilage degeneration, the changes in the radial head could
      be divided into four types. The mode of radial head cartilage degeneration
      correlated well with cartilage degeneration in the radiohumeral articulation and
      also with osteoarthritis of the elbow joint. Simplistically, one could classify
      elbow joint osteoarthritis by knowing the extent of radial head degeneration.

PMID- 22971731
TI  - Ubiquitin-conjugating enzyme E2-like gene associated to pathogen response in
      Concholepas concholepas: SNP identification and transcription expression.
AB  - Ubiquitin-conjugated E2 enzyme (UBE2) is one of the main components of the
      proteasome degradation cascade. Previous studies have shown an increase of
      expression levels in individuals challenged to some pathogen organism such as
      virus and bacteria. The study was to characterize the immune response of UBE2
      gene in the gastropod Concholepas concholepas through expression analysis and
      single nucleotide polymorphisms (SNP) discovery. Hence, UBE2 was identified from
      a cDNA library by 454 pyrosequencing, while SNP identification and validation
      were performed using De novo assembly and high resolution melting analysis.
      Challenge trials with Vibrio anguillarum was carried out to evaluate the relative
      transcript abundance of UBE2 gene from two to thirty-three hours post-treatment.
      The results showed a partial UBE2 sequence of 889 base pair (bp) with a partial
      coding region of 291 bp. SNP variation (A/C) was observed at the 546th position.
      Individuals challenged by V. anguillarum showed an overexpression of the UBE2
      gene, the expression being significantly higher in homozygous individuals (AA)
      than (CC) or heterozygous individuals (A/C). This study contributes useful
      information relating to the UBE2 gene and its association with innate immune
      response in marine invertebrates.

PMID- 22971730
TI  - Dietary protein in weight management: a review proposing protein spread and
      change theories.
AB  - A large volume of human clinical data supports increased dietary protein for
      favorable changes to body composition, but not all data are conclusive. The aim
      of this review is to propose two theories, "protein spread theory" and "protein
      change theory" in an effort to explain discrepancies in the literature. Protein
      spread theory proposed that there must have been a sufficient spread or %
      difference in g/kg/day protein intake between groups during a protein
      intervention to see body composition and anthropometric differences. Protein
      change theory postulated that for the higher protein group, there must be a
      sufficient change from baseline g/kg/day protein intake to during study g/kg/day
      protein intake to see body composition and anthropometric benefits. Fifty-one
      studies met inclusion criteria. In studies where a higher protein intervention
      was deemed successful there was, on average, a 58.4% g/kg/day between group
      protein intake spread versus a 38.8% g/kg/day spread in studies where a higher
      protein diet was no more effective than control. The average change in habitual
      protein intake in studies showing higher protein to be more effective than
      control was +28.6% compared to +4.9% when additional protein was no more
      effective than control. Providing a sufficient deviation from habitual intake
      appears to be an important factor in determining the success of additional
      protein in weight management interventions. A modest increase in dietary protein
      favorably effects body composition during weight management interventions.

PMID- 22971733
TI  - The technique and efficacy of axillary catheter analgesia as an adjunct to
      distraction elbow arthroplasty: A prospective study.
AB  - A prospective study was done on 99 consecutive patients who underwent distraction
      elbow arthroplasty and postoperative continuous passive motion from 1986 to 1992.
      Postoperative axillary catheter infusion in 73 patients was compared with patient
      controlled analgesia-opioid treatment in 26 patients. Group comparisons for
      analgesia, complications, time to initiation, and tolerance of postoperative
      continuous passive motion were made. The postoperative axillary catheter infusion
      group was more comfortable and had better postoperative continuous passive motion
      compliance than did the patient-controlled analgesia-opioid group. The
      postoperative axillary catheter infusion group had a 2.7% (2 of 73) incidence of
      respiratory toxicity. There was an 11.5% (3 of 26) incidence of respiratory
      depression in the patient-controlled analgesia-opioid group. Final arc range of
      motion was similar between postoperative axillary catheter infusion and patient
      controlled analgesia-opioid groups. The data support the hypothesis that
      postoperative axillary catheter infusion provides better patient comfort and
      earlier postoperative continuous passive motion initiation, but they do not show
      additional improvement in the final arc of motion after distraction elbow
      arthroplasty as compared with a patient-controlled analgesia-opioid treatment
      group.

PMID- 22971734
TI  - Suprascapular nerve entrapment: Diagnosis and results of treatment.
AB  - Twenty-eight patients with suprascapular nerve entrapment confirmed by
      electromyographic and nerve conduction studies were identified and treated. This
      diagnosis was not previously suspected in these patients, because 22 previous
      operations had been done in 13 of the patients. In 26 patients the authors
      performed a release of the suprascapular ligament. One patient required a second
      operation to release an incompletely divided ligament. The recommended surgical
      technique requires elevation of the trapezius muscle from the scapular spine. The
      trapezius is retracted cephalad, and the supraspinatus is retracted posteriorly.
      The suprascapular ligament is resected. Notch resection is unnecessary in the
      usual case. There were 25 excellent or good results and one fair result.
      Suprascapular nerve entrapment should be suspected and included in the
      differential diagnosis of vogue shoulder pain.

PMID- 22971735
TI  - A spherical model analyzing shoulder motion in overhand and sidearm pitching.
AB  - An accurate measurement of shoulder movement in pitching is indispensable in
      clarifying the causes of shoulder problems stemming from baseball pitching and in
      preventing these disorders. In this investigation, three-dimensional imaging and
      electromyography were performed during pitching. Two different pitching methods
      (overhand throwing and sidearm throwing) of 35 amateur pitchers were analyzed
      with a high-speed video imaging system. In 25 subjects shoulder rotation during
      pitching was measured with a compact camera attached to the shoulder. In 21
      subjects, the electromyographic activity of the biceps and triceps muscles during
      pitching was examined. Image analysis showed little difference in shoulder
      movement between the two pitching methods for each subject, while individual
      subjects had specific shoulder movements. Electromyography demonstrated the role
      of the triceps muscle during pitching. The clinical ramifications of these
      analyses may be very useful.

PMID- 22971736
TI  - Glenohumeral movement patterns after puncture of the joint capsule: An
      experimental study.
AB  - In on experimental series comprising 22 shoulder specimens obtained at autopsy,
      we investigated the influence of an intact capsule on glenohumeral stability.
      Puncture of the capsule resulted in significant glenohumeral translation in
      unloaded and loaded specimens during shoulder abduction. A maximum of 16.6 mm of
      distal translation was observed at 20 degrees  of abduction. Concomitant with
      this translation the humerus spontaneously rotated externally, with a maximum
      rotation of 15.8 degrees  at 50 degrees  of abduction. After venting the capsule,
      anterior and posterior translation and external rotation were increased
      significantly. Maximum total increase in anteroposterior translation was 14 mm at
      30 degrees  of abduction. The external rotation was increased up to 7.1 degrees 
      at 40 degrees  of abduction. These findings indicate that studies evaluating
      glenohumeral instability are compromised unless the translations resulting from
      capsular venting ore corrected. Evaluation of shoulder stability should be
      performed before violation of the intraarticular pressure mechanisms.

PMID- 22971737
TI  - Efficacy and pitfalls of the STATAK soft-tissue attachment device for the Bankart
      repair.
AB  - This report describes the results of Bankart repair with the use of a soft-tissue
      attachment device in 15 consecutive patients with traumatic, recurrent anterior
      instability of the shoulder. The mean operative time was 18 minutes shorter when
      compared with our previous series with the traditional transosseous suture
      technique. The surgical outcome was satisfactory in 12 patients and
      unsatisfactory in three. In two of these three patients, incomplete anchoring of
      the device seemed to have caused subluxation after the operation. Thus this
      device has the potential to shorten the operative time, but great care must be
      taken to securely position it below the cortical surface.

PMID- 22971738
TI  - Isolated avulsion fracture of the lesser tuberosity of the humerus: A case
      report.
AB  - Isolated avulsion fractures of the lesser tuberosity are extremely rare. A 24
      year-old woman fell on her back as her arm was forcibly extended and adducted.
      Radiographs revealed a small fragment of bone beneath the glenoid. Axillary
      radiography showed the bone fragment and a bone defect of the lesser tuberosity.
      Computed tomography scan clearly demonstrated those findings. Surgery was
      performed 3 weeks after the occurrence of the injury. The bone fragment was
      reduced and fixed by means of two screws. After 3 weeks, light exercise was
      started. At follow-up 7 months later she had no complaints. Most reported cases
      involved sudden contraction of the subscapularis tendon. This type of fracture is
      sometimes misdiagnosed; computed tomography scan is useful for diagnosis.
      Previously reported cases have similarly demonstrated a good outcome after
      surgery, except in cases involving children.

PMID- 22971740
TI  - Acoustofluidics 19: ultrasonic microrobotics in cavities: devices and numerical
      simulation.
AB  - Acoustic radiation forces are increasingly used for the handling of micron sized
      particles (cells, functionalized beads, etc.) suspended in a fluid in the chamber
      of a manipulation device. The primary radiation forces arise as a nonlinear
      effect when an acoustic wave interacts with a particle. For specific robotic
      applications, precise control of the acoustic field in the cavity is important,
      which is excited, for example, by piezoelectric transducers attached to the
      device. Based on Gor'kov's potential the relevant forces on spherical particles
      can be computed. The field can be controlled by varying the excitation
      parameters: chamber and electrode configuration, as well as frequency, amplitude
      and phase of the excitation and their modulation. In the first part of the
      present tutorial, a number of examples are described: displacement and rotation
      of particles in micro machined chambers and macroscopic transport of particles in
      a larger chamber. In the second part, numerical tools (Finite Volume Method,
      COMSOL) are used to model the interaction of the acoustic field with a particle
      beyond a Gor'kov potential: viscosity, effects of walls near particles and
      acoustic radiation torque to rotate the particle. Excellent agreement between the
      various methods has been found.

PMID- 22971743
TI  - Household preparedness for public health emergencies--14 states, 2006-2010.
AB  - Populations affected by disaster increase the demand on emergency response and
      public health systems and on acute care hospitals, often causing disruptions of
      services. Household preparedness measures, such as having a 3-day supply of food,
      water, and medication and a written household evacuation plan, can improve a
      population's ability to cope with service disruption, decreasing the number of
      persons who might otherwise overwhelm emergency services and health-care systems.
      To estimate current levels of self-reported household preparedness by state and
      sociodemographic characteristics, CDC analyzed Behavioral Risk Factor
      Surveillance System (BRFSS) survey data collected in 14 states during 2006-2010.
      The results of this analysis indicated that an estimated 94.8% of households had
      a working battery-operated flashlight, 89.7% had a 3-day supply of medications
      for everyone who required them, 82.9% had a 3-day supply of food, 77.7% had a
      working battery-operated radio, 53.6% had a 3-day supply of water, and 21.1% had
      a written evacuation plan. Non-English speaking and minority respondents,
      particularly Hispanics, were less likely to report household preparedness for an
      emergency or disaster, suggesting that more outreach activities should be
      directed toward these populations.

PMID- 22971742
TI  - Analgesic efficacy and clinical acceptability of adjunct pre-emptive intravenous
      tramadol in midazolam sedation for third molar surgery.
AB  - INTRODUCTION: This study aims to compare two routine procedures of sedation, with
      and without intravenous adjunct analgesia, in third molar surgery regarding
      postoperative pain and consumption of analgesics. MATERIAL AND METHODS: In a
      randomized, controlled, single-blinded procedure, 87 men and women aged 18-44
      years were divided into two treatment groups, midazolam + tramadol (M + T) and
      midazolam + saline (M + S), and one control group (C), with no additional
      medication. After removal of a third lower molar, patients recorded postoperative
      pain on a visual analog scale (VAS) and consumption of analgesics during the
      first day after surgery. RESULTS: Time from the end of operation until first
      rescue pill (400 mg Ibuprofen tablet) differed significantly between the M + S
      group (193 min) and the C group (110 min) (p = 0.001) as well as the M + T group
      (157 min) and the C group (p = 0.049). The study did not show any significant
      reduction of postoperative pain, VAS, after third molar surgery in patients who
      received adjunct pre-emptive intravenous administration of 1 mg/kg tramadol under
      midazolam sedation. DISCUSSION AND CONCLUSION: The lack of significant difference
      between the study and placebo groups indicates that tramadol at 1 mg/kg might be
      an insufficient dose, though the suitability for tramadol in oral and
      maxillofacial surgery has already been settled in other studies.

PMID- 22971741
TI  - Necrosis-like death can engage multiple pro-apoptotic Bcl-2 protein family
      members.
AB  - Necroptosis is a physiologically relevant mode of cell death with some well
      described initiating events, but largely unknown executioners. Here we
      investigated necrostatin-1 (Nec-1) sensitive death elicited by different
      necroptosis stimuli in L929 mouse fibrosarcoma cells, mouse embryonic fibroblasts
      (MEF) and bone marrow-derived macrophages. We found that TNFalpha- or zVAD
      induced necroptosis occurs independently of the recently implicated executioners
      Bmf or PARP-2, but can involve the Bcl-2 family proteins Bid and Bak.
      Furthermore, this type of necroptosis is associated with mitochondrial cytochrome
      c release and partly sensitive to cyclosporine A inhibition, suggesting a cross
      talk with the mitochondrial permeability transition pore. Necroptosis triggered
      by cadmium (Cd) exposure caused fully Nec-1-sensitive and caspase-independent
      death in L929 cells that was associated with autocrine TNFalpha-mediated feed
      forward signalling. In MEF Cd-exposure elicited a mixed mode of cell death that
      was to some extent Nec-1-sensitive but also displayed features of apoptosis. It
      was partly dependent on Bmf and Bax/Bak, proteins typically considered to act pro
      apoptotic, but ultimately insensitive to caspase inhibition. Overall, our study
      indicates that inducers of "extrinsic" and "intrinsic" necroptosis can both
      trigger TNF-receptor signalling. Further, necroptosis may depend on mitochondrial
      changes engaging proteins considered critical for MOMP during apoptosis that
      ultimately contribute to caspase-independent necrotic cell death.

PMID- 22971744
TI  - Assessment of household preparedness through training exercises--two metropolitan
      counties, Tennessee, 2011.
AB  - Public health emergency preparedness involves improving both workforce and
      household capacity to manage disasters. To improve preparedness at both levels,
      the Tennessee Department of Health (TDH) formed a Rapid Assessment of Populations
      Impacted by Disasters (RAPID) team. In 2011, the team used Community Assessment
      for Public Health Emergency Response (CASPER) two-stage cluster sampling
      methodology to measure household preparedness for disasters or emergencies in two
      metropolitan counties. In the two counties, 23% and 31% of households reported
      being "well-prepared" to handle disasters or emergencies, 43% and 44% reported
      being "somewhat prepared," and 25% and 20% reported being "not at all prepared."
      As a result of this experience, RAPID teams were able to improve their methods,
      streamline processes, and create a better community assessment toolkit. To
      increase preparedness at both the community and workforce levels, public health
      departments should assess community preparedness to inform the planning process
      and provide field training and exercise opportunities for public health workers.

PMID- 22971745
TI  - Tuberculosis genotyping--United States, 2004-2010.
AB  - Tuberculosis (TB) genotyping is a laboratory-based genetic analysis of the
      bacteria that cause TB disease (i.e., any of the organisms in the Mycobacterium
      tuberculosis complex). When combined with epidemiologic data, TB genotyping has
      sufficient discriminatory power to help find TB cases likely to be in the same
      chain of transmission or determine that cases are not related. Since 2004,
      >70,000 M. tuberculosis isolates have been genotyped through partnerships between
      CDC, national genotyping laboratories, and state and local public health
      departments, with a goal to genotype at least one M. tuberculosis isolate for
      each case of culture-positive TB in the United States. National genotype
      surveillance coverage, or the proportion of culture-positive TB cases with a
      genotyped isolate, increased from 51.2% in 2004 to 88.2% in 2010. The TB
      Genotyping Information Management System (TB GIMS), accessible to public health
      departments through a secure, online web portal, was launched in 2010. TB GIMS
      enables systematic collection of genotyping results, which have been available
      since 2004, and integrates those results with epidemiologic, geographic,
      demographic, and clinical data collected by the National TB Surveillance System
      (NTSS) since 1993. Genotyping timeliness, represented by the median time from
      specimen collection until linked genotyping results and surveillance data are
      available to TB GIMS users, improved from 22 weeks in July 2010 to 11 weeks in
      December 2010. These improvements in genotype surveillance coverage and
      timeliness will improve outbreak detection efforts and enable more in-depth
      studies of TB epidemiology, leading to better use of limited public health
      resources.

PMID- 22971746
TI  - Notes from the field: Highly pathogenic avian influenza A (H7N3) virus infection
      in two poultry workers--Jalisco, Mexico, July 2012.
AB  - During June-August 2012, Mexico's National Service for Health, Safety, and Food
      Quality reported outbreaks of highly pathogenic avian influenza (HPAI) A (H7N3)
      virus in poultry on farms throughout the state of Jalisco. This report describes
      two cases of conjunctivitis without fever or respiratory symptoms caused by HPAI
      A (H7N3) virus infection in humans associated with exposure to infected poultry.

PMID- 22971748
TI  - Inhibitory effects of Yangzheng Xiaoji on angiogenesis and the role of the focal
      adhesion kinase pathway.
AB  - Angiogenesis is an essential event during the excessive growth and metastatic
      spread of solid tumours. Anti-angiogenic agents have become a new choice of
      therapy for patients with cancer. In the present study, we investigated the
      potential effect of Yangzheng Xiaoji, a traditional Chinese medicinal formula
      presently used in the treatment of several solid tumours including liver cancer
      and gastric cancer, on angiogenesis, in vitro. The human vascular endothelial
      cell line HECV was used. A Matrigel-based sandwich tubule formation assay was
      employed to assess in vitro angiogenesis, a colorimetric method for assessing in
      vitro cell growth. Electric cell-substrate impedance sensing (ECIS) was used to
      evaluate the adhesion and migration of endothelial cells. The effects on
      activation of focal adhesion kinase (FAK) were evaluated using western blotting
      and immunofluorescence methods. Yangzhen Xiaoji extract DME25 significantly
      inhibited tube formation (p=0.046 vs control). This was seen together with a
      concentration-dependent inhibition on cell-matrix adhesion and cellular
      migration. It was demonstrated that the focal adhesion kinase (FAK) inhibitor
      PF557328 had a significant synergistic effect on DME25-induced inhibition of cell
      adhesion, migration and tube formation. The study showed that DME25 inhibited the
      phosphorylation of FAK in endothelial cells. In conclusion, Yangzhen Xiaoji has a
      marked effect on angiogenesis, in vitro and that this effect is at least partly
      mediated by the focal adhesion kinase (FAK) pathway.

PMID- 22971749
TI  - The conserved 12-amino acid stretch in the inter-bromodomain region of BET family
      proteins functions as a nuclear localization signal.
AB  - The bromodomain and extraterminal (BET) family is a group of chromatin-binding
      proteins characterized by two bromodomains, an extraterminal (ET) domain, and
      several other conserved regions of unknown function. In humans, the BET family
      consists of four members, BRD2, BRD3, BRD4 and BRDT, that all normally localize
      to the nucleus. We identified a 12-amino acid stretch in the inter-bromodomain
      region that is perfectly conserved among the BET family members. We deleted these
      residues and expressed the mutant proteins in HEK293T cells to investigate the
      function of this motif. We found that the deletion of this motif alters the
      localization of BET proteins. Mutated BRD3 and BRD4 were excluded from the
      nucleus, and BRDT was found to be diffused throughout the nucleus and cytoplasm.
      Although the mutant BRD2 remained predominantly in the nucleus, a punctate
      distribution was also observed in the cytosol. It has been reported that a
      conserved motif between the second bromodomain and the ET domain serves as a
      nuclear localization signal for BRD2. Nevertheless, BET mutants lacking the
      reported nuclear localization signal motif but retaining the 12-amino acid
      stretch resided in the nucleus. Furthermore, these mutants were diffused
      throughout the cytoplasm when the 12 residues were removed. These results
      indicate that the conserved amino acid stretch in the inter-bromodomain region of
      the BET family functions as a nuclear localization signal.

PMID- 22971750
TI  - Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs genetic
      polymorphisms and plasma levels in hypertensive disorders of pregnancy.

PMID- 22971751
TI  - Prevalence, risk factors and awareness of hypertension in India: a systematic
      review.
AB  - Indians have high rates of cardiovascular disease. Hypertension (HTN) is an
      important modifiable risk factor. There are no comprehensive reviews or a
      nationally representative study of the burden, treatments and outcomes of HTN in
      India. A systematic review was conducted to study the trends in prevalence, risk
      factors and awareness of HTN in India. We searched MEDLINE from January 1969 to
      July 2011 using prespecified medical subject heading (MeSH) terms. Of 3372
      studies, 206 were included for data extraction and 174 were observational
      studies. Prevalence was reported in 48 studies with sample size varying from 206
      to 167 331. A significant positive trend (P<0.0001) was observed over time in
      prevalence of HTN by region and gender. Awareness and control of HTN (11 studies)
      ranged from 20 to 54% and 7.5 to 25%, respectively. Increasing age, body mass
      index, smoking, diabetes and extra salt intake were common risk factors. In
      conclusion, from this systematic review, we record an increasing trend in
      prevalence of HTN in India by region and gender. The awareness of HTN in India is
      low with suboptimal control rates. There are few long-term studies to assess
      outcomes. Good quality long-term studies will help to understand HTN better and
      implement effective prevention and management programs.

PMID- 22971752
TI  - The association between apolipoprotein E gene polymorphisms and essential
      hypertension: a meta-analysis of 45 studies including 13,940 cases and 16,364
      controls.
AB  - The apolipoprotein E single-nucleotide polymorphisms are among the potential
      candidate genes that may serve as modulators in susceptibility to essential
      hypertension. In an effort to clarify earlier inconclusive results, we performed
      a meta-analysis of population-based case-control genetic association studies.
      Random-effects methods were applied on summary data in order to combine the
      results of the individual studies. We identified in total 45 studies, including
      13 940 hypertensive cases and 16 364 controls. The contrast of E4 carriers versus
      non-carriers yielded an overall odds ratio (OR) of 1.16 (95% confidence interval
      (CI): 1.02, 1.31), whereas the contrast of E4 allele versus the others in a
      subtotal of 6617 cases and 7330 controls, yielded an OR of 1.39 (95% CI: 1.12,
      1.72). There was moderate evidence of publication bias in both contrasts, which
      was eliminated after excluding studies not in Hardy-Weinberg equilibrium.
      Subgroup analyses revealed that significant estimates arose from studies on Asian
      populations, as opposed to the Caucasian ones. Furthermore, no evidence of
      publication bias was demonstrated in the comparisons within this subgroup. Our
      results are consistent with recent meta-analyses but show that the association is
      weaker than that has been previously demonstrated. Further studies are needed in
      order to fully address questions about the etiological mechanism of the
      particular association, as well as to study the effect in populations of African
      descent.

PMID- 22971753
TI  - Within-visit blood pressure variability: relevant factors in the general
      population.
AB  - The objective of this study was to use a nationwide epidemiological survey to
      investigate the factors that affect within-visit blood pressure (BP) variability.
      We analyzed the Korean National Health and Nutrition Examination Survey (KNHNES)
      data for 2005 (n=5488). We examined three within-visit BP variability parameters
      that include the following: the alarm reaction (AR), defined as the first BP
      reading minus the third BP reading; the BP discrepancy, defined as the maximal BP
      reading minus the minimal BP reading (DeltaBPmax); and the s.d. (BPSD). Age,
      fasting glucose, eGFR, total cholesterol, LDL cholesterol, and the metabolic
      syndrome (MetS) score were the relevant factors that affected the systolic AR,
      DeltaSBPmax and SBPSD. Multiple linear regression models revealed that age
      (P<0.0001), the office systolic BP (SBP) level (P<0.0001), the MetS score
      (P<0.0001), the female gender (P=0.007) and the eGFR (P=0.049) were independently
      associated with the systolic AR, whereas age (P<0.0001), the office SBP level
      (P<0.0001), and the female gender (P=0.024 and 0.022) were independently
      associated with DeltaSBPmax and SBPSD, respectively. Within-visit BP variability,
      especially the variability associated with the SBP, was significantly associated
      with increased age, female gender and cardiovascular risk factors, such as
      hypertension, low eGFR and adverse glucose and lipid profiles. In addition,
      increased age, female gender, the eGFR and the MetS score were independently
      relevant factors that affected the systolic AR. Systolic within-visit BP
      variability and systolic AR are associated with cardiovascular risk factors.

PMID- 22971754
TI  - Dietary fructose in relation to blood pressure and serum uric acid in adolescent
      boys and girls.
AB  - Evidence that fructose intake may modify blood pressure is generally limited to
      adult populations. This study examined cross-sectional associations between
      dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents
      aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine)
      Study. Energy-adjusted fructose intake was derived from 3-day food records, serum
      uric acid concentration was assessed using fasting blood and resting blood
      pressure was determined using repeated oscillometric readings. In multivariate
      linear regression models, we did not see a significant association between
      fructose and blood pressure in boys or girls. In boys, fructose intake was
      independently associated with serum uric acid (P<0.01), and serum uric acid was
      independently associated with systolic blood pressure (P<0.01) and mean arterial
      pressure (P<0.001). Although there are independent associations, there is no
      direct relationship between fructose intake and blood pressure. Our data suggest
      that gender may influence these relationships in adolescence, with significant
      associations observed more frequently in boys than girls.

PMID- 22971755
TI  - Cell adhesion and migration on nanopatterned substrates and their effects on cell
      capture yield.
AB  - With scanning electron microscopy analysis, we investigated the role of nanoscale
      topography on cellular activities; e.g. cell adhesion and spreading by culturing
      A549 cells (human lung carcinoma cell line cells) for 1-48 h on three sets of
      nanostructures; quartz nanopillars (QNPs), silicon nanopillars and silicon
      nanowire (SiNW) arrays, along with planar glass substrates. We found that cells
      on QNP arrays developed a longer shape than those on SiNW arrays. In addition, we
      studied how cell morphologies influence the cell-capture yield on the three sets
      of nanostructures. This research showed that the filopodial formations were
      directing the cell-capture yield on nanostructured substrates. This finding
      implies the possibility of using nanoscale topography features to control the
      filopodial formation including extension and migration from the cells. Using
      streptavidin-functionalized SiNW substrate, we further demonstrated a
      substantially higher yield (~91.8 +/- 5.9%) than the planar glass wafers (~24.1
      +/- 7.5%) in the range of 200-3000 cells.

PMID- 22971756
TI  - Effect of cycloheximide on epidermal growth factor receptor trafficking and
      signaling.
AB  - Cycloheximide is the most common protein synthesis inhibitor, and is believed to
      specifically inhibit the cytoplasmic protein synthesis. Here we demonstrate that
      cycloheximide induces internalization and redistribution of EGF receptor to early
      endosomes in HeLa cells independent of receptor tyrosine phosphorylation, but
      dependent on p38 MAPK activity. Degradation of EGF receptor or its downstream
      effectors was not observed. EGF-induced activation of ERK1/2 was inhibited upon
      pre-treatment with cycloheximide, but did not activate JNK. The observed effects
      of treatment with cycloheximide alone are significant and therefore results
      involving the use of cycloheximide for inhibition of protein synthesis must be
      interpreted with caution.

PMID- 22971757
TI  - Mitral valve mobility.

PMID- 22971758
TI  - Complex anomalies of type 1 proatlantal intersegmental artery and aortic arch
      variations.
AB  - PURPOSE: We report a case of type 1 proatlantal intersegmental artery (PIA)
      associated with multiple anomalies of the aortic arch, and discuss the possible
      embryonic mechanism and clinical importance of the multiple cerebrovascular
      variants in this patient. METHODS: A 65-year-old woman with dizziness underwent
      cerebral magnetic resonance (MR) imaging and head and neck MR angiography using a
      3-tesla scanner and computed tomography (CT) angiography using a 64-slice
      multidetector CT scanner. RESULTS: MR and CT angiography demonstrated an aneurysm
      of the distal end of the azygos anterior cerebral arteries and hypoplasia of the
      proximal right vertebral artery (VA) with an anastomotic artery, between the
      right internal carotid artery (ICA) and distal right VA that passed through the
      foramen magnum, indicating a type 1 PIA. She also demonstrated an aberrant right
      subclavian artery (ARSA) with hypoplasia of the right VA, and the left VA arose
      directly from the aortic arch. CONCLUSION: To our knowledge, this is the first
      report of a type 1 PIA associated with multiple vascular anomalies of the aortic
      arch, such as ARSA and origin of the left VA from the arch. In cases of
      persistent anastomoses between the carotid and vertebrobasilar arteries, such as
      PIAs, imaging examination should include the aortic arch to identify associated
      vascular variations.

PMID- 22971759
TI  - 3-T MRI of the biliary tract variations.
AB  - PURPOSE: The gallbladder and the biliary tract are structures in close connection
      with the adjacent organs and may show a number of variations and anomalies. It is
      therefore important for surgical purposes to know their anatomy and variations in
      detail. Various methods are used in the imaging of the variations of the biliary
      tract and its pathologies, including ultrasonography, computed tomography; direct
      cholangiographic methods like endoscopic retrograde cholangiopancreatography,
      percutaneous transhepatic cholangiography, intravenous cholangiography and T-tube
      cholangiography, as well as indirect methods like magnetic resonance
      cholangiopancreatography (MRCP) or cholescintigraphy. The aim of this study is to
      investigate the frequency of the anatomic variations of the biliary tract using 3
      T MRCP and to compare the findings with the data in the literature. MATERIALS AND
      METHODS: For the purposes of this study, patients who underwent MRCP at our
      hospital (Dicle University Hospital) between November 2009 and February 2012 were
      investigated retrospectively. A total of 590 patients (between 6 and 88 years of
      age; mean age: 51 +/- 9 years) were included in the study. The MRCP imaging was
      carried out with an magnetic resonance imaging (MRI) device supplied with 3-T
      magnetic power and by obtaining T2-weighted images through the single-shot fast
      spin echo technique using the standard body coil. The axial and coronal source
      images and the reformatted images were evaluated together in terms of the
      possible anatomic variations. RESULTS: Among the 590 patients included in the
      study, of 233 (39.5 %) showed anatomic variations at different levels in the
      intra- and extrahepatic biliary tracts. Among these variations, a right posterior
      hepatic duct insertion to the left hepatic duct at the level of the bifurcation
      has been observed in 71 patients (12.1 %), trifurcation was observed in 30
      patients (5.1 %) and insertion into the main hepatic duct at the proximal aspect
      of the cystic duct was observed in 18 patients (3.1 %). At the level of the
      cystic duct, medial insertion of the cystic duct was viewed in 58 patients (9.8
      %), distal medial insertion was seen in 40 patients (6.8 %), a short cystic duct
      was detected in 10 patients (1.7 %), pancreatobiliary junction anomaly was viewed
      in two patients (0.4 %) and duplicate anatomic variations have been observed in
      42 patients (7.2 %). CONCLUSION: MRCP studies conducted using 3-T MRI devices may
      reveal similar or greater numbers of variations when compared to the existing
      MRCP studies in the literature. 3-T MRI shows a couple of variations. Pointing
      out these anatomical variations before the surgical intervention may prevent
      possible iatrogenic traumas. Donors with unsuitable variations for liver
      transplant may be spotted out at an early phase through the MRCP and certain
      operations with a high morbidity rate may thus be avoided.

PMID- 22971761
TI  - Laparoscopic treatment of genitourinary fistulae.
AB  - We present the laparoscopic management of genitourinary fistulae, mainly five
      types of fistulae, vesicovaginal, ureterovaginal, vesicouterine, rectourethral
      and rectovesical  fistula. Vesicovaginal fistula (VVF) is mostly secondary to
      urogynecologic procedures in developed countries, abdominal hysterectomy being
      the main cause of this  condition;  they represent 84.9% of the genitourinary
      fistulae (1).Management has been described for this type of fistula, where low
      success  rate (7-12%) has been reported. Ureterovaginal  fistulas may occur
      following pelvic surgery, particularly gynecological procedures, or as a result
      of vaginal foreign bodies or stone fragments after shock wave lithotripsy, 
      patients typically present with global and persistent urine leakage through the
      vagina, this causes patient discomfort, distress, and typically protection is
      used to stay dry, the initial management is often conservative but typically
      fails.  Vesicouterine fistula is a rare condition that only occurs in 1 to 4% of
      genitourinary fistulas, the primary cause is low segment cesareansection, and
      clinically  presents in  three different forms, which will be described.
      Treatment of this type of fistulae has been conservative,with hormone therapy and
      surgery, depending on the presenting  symptoms. Recto-urinary (rectovesical and
      rectourethral) fistulae (RUF) are uncommon and can be difficult to manage
      clinically. Although they may  develop  in patients  with inflammatory bowel
      disease and perirectal abscesses, rectourethral fistula frequently result as an
      iatrogenic complication of extirpative or ablative prostate  procedures.
      Rectovesical fistula usually develops following radical prostatectomy, and occurs
      along the vesicourethral anastomotic line or along the suture line of  a
      posterior "racquet-handle" closure of the bladder. Conservative management
      consisting of urinary diversion, broad-spectrum antibiotics and  parenteral 
      nutrition is  often initially attempted but these measures often fail. Timing of
      repair is often individualized mainly according to the etiology, delay of
      diagnosis, size of  fistula, the first or subsequent repairs, and the general
      condition of the patient. Different surgical techniques for the management of RUF
      have been reported.  Encouraged by our experience in minimally invasive  surgery
      we present the laparoscopic approach.

PMID- 22971762
TI  - [Laparoscopic treatment of genitourinary fistulae. Editorial comment].

PMID- 22971763
TI  - Importance of previous transurethral resection of the prostate before eerpe.short
      term functional outcomes in a single surgeon series.
AB  - OBJECTIVES: Laparoscopic Radical Prostatectomy (LRP) is technically a very
      demanding procedure and potentially even more challenging in patients with
      previous  transurethral resection (TURP). This study evaluates the impact of
      previous TURP on the short-term functional outcome of patients undergoing
      extraperitoneal  LRP. METHODS: Retrospective analysis of a prospectively
      collected database, comprising a single-surgeon cohort of 155 consecutive LRP
      cases, 19 of which had previous history of TURP. Demographics, clinical and
      functional outcomes were evaluated and compared among patients with and without
      previous TURP. Multivariate analysis  was performed to identify potential
      variables independently associated with continence outcomes. Incontinence was
      defined as the need of more than 1 pad/day.  Potency was defined as the ability
      for sexual intercourse with or without the use of phosphodiesterase inhibitors.
      RESULTS: Demographic and clinical variables were comparable among the two study
      groups. Neurovascular bundle preservation was possible in 26% and 37%   of
      patients  with and without previous TURP, respectively. No major complications
      were recorded and the incidence of minor complications was comparable. Overall
      continence  rate at 3 months was 82,58%, for the entire cohort. Subset analysis
      demonstrated a 3-month continence rate of 73.7% vs. 83.8%  (p>0.05)  in patients 
      with and without  TURP, respectively. Multivariate analysis demonstrated age, BMI
      and ASA were variables independently associated with continence outcomes. In the
      cohort of patients  with previous TURP, 2 out of 7 undergoing preservation
      recovered erections, with a mean follow up of 15.5 months, comparable to the 30%
      achieved in patients without TURP and nerve sparing procedure. CONCLUSIONS:
      Laparoscopic Radical Prostatectomy in patients with previous TURP is feasible,
      with complication rates and short-term functional outcomes comparable  to those
      in patients without previous resection.

PMID- 22971764
TI  - Early treatment of penile fractures: our experience.
AB  - OBJECTIVES: To report our experience in early surgery of penile fractures.
      METHODS: We review retrospectively all the cases that underwent surgery at our
      center from 1989 to 2009, with a total of 24. RESULTS: The cause of the fracture
      was sexual intercourse in most cases, and in all of them, surgical management was
      performed according to clinical  presentation and physical exploration. In only 7
      cases an ultrasound was performed as a complementary test. DISCUSSION: Early
      surgery allows prompt resolution of the problem with excellent functional
      outcomes and little side effects. CONCLUSIONS: The prognosis after emergency
      surgery was excellent in this review.

PMID- 22971765
TI  - Prevalence and risk factors of erectile dysfunction and testosterone deficiency
      symptoms in a rural population in Uganda.
AB  - OBJECTIVES: To determine the prevalence and risk factors of erectile dysfunction
      (ED) and the prevalence of hypogonadism symptoms in Buluba, a rural population in
      Uganda. METHODS: Prospective, consecutive, cross-sectional study was conducted
      between September and December 2010. 902 men attending the outpatient clinic of
      Saint Francis Hospital in Buluba were enrolled. From these 902 men, 204 had been
      previously diagnosed as HIV+ followed in a specific HIV outpatient clinic in the
      same centre. Variables age, weight, height, tobacco use and drinking habits,
      Erection Hardness Score and Aging Male Symptoms Scale (AMSS), as well as
      Hypertension, Diabetes, Dyslipidemia, lung diseases, peptic ulcer, urinary
      symptoms and HIV were prospectively recorded. A multivariate analysis was used to
      analyze the variables related to erectile function and AMSS. RESULTS: Mean age
      was 39+/-11,8 years. ED rate was 47,8% (Mild ED 28,8%; Moderate 14%; Severe 5%).
      In the multivariate analysis, variables age (Odds ratio (OR) 1,032), HIV+ (OR
      11,280), AMSS (OR 1,138) and AMSS>=50 (OR 1,164) were related to ED. When
      excluding HIV+ population, 36,8% of men suffered ED (Mild ED 23%; Moderate 10,2%;
      Severe 3,6%). 5,7% of men had severe symptoms(>=50) of hypogonadism according to
      AMSS. No clinical variable was related to the presence of AMSS>=50 in the
      multivariate analysis. CONCLUSIONS: The rate of ED in a rural milieu in Uganda is
      high. Variables age, AMSS and AMSS>=50 and HIV+ were related to ED. The rate of
      AMSS>=50 was 5,7%. No variable was found to be related to AMSS>=50.

PMID- 22971766
TI  - Secondary bladder amyloidosis: a new case report.
AB  - OBJECTIVE: To report a new case of secondary bladder amyloidosis,
      beinginvolvement of the urinary bladder by amyloidosis infrequent on the basis of
      very few  references in the literature (we estimate the number of cases of
      secondary vesical amyloidosis reported to be around 30). METHODS/RESULTS: The
      case presented here corresponds to secondary bladder amyloidosis in a patient
      suffering from Still's disease, who began with hematuria  and ended dying.
      CONCLUSION: Secondary bladder amyloidosis constitutes a very infrequent
      pathology, and we can distinguish between primary forms of bladder amyloidosis
      and  systemic forms of amyloidosis that affect the urinary bladder (secondary
      bladder amyloidosis). It is associated in the majority of patients with
      rheumatoid  arthritis that has evolved over a long period. Clinical diagnosis is
      difficult, and it is necessary to carry out differential diagnosis with bladder
      tumours.  The pathological and immunohistochemical studies confirm the diagnosis.

PMID- 22971767
TI  - Epithelioid angiomyolipoma presenting as an urothelial.
AB  - OBJECTIVE: Renal angiomyolipoma is a mesenchymal neoplasm composed of dysmorphic
      blood vessels, smooth muscle, and adipose tissue. Epithelioidangiomyolipoma is an
      uncommon variant considered potentially malignant. We report a case of renal
      epithelioid angiomyolipoma suspicious for urothelialcarcinoma of renal pelvis.
      METHODS: A 50-year-old woman with a 3-day history of macroscopic hematuria and CT
      scan showing a tumor arising from the left renal pelvis suspicious for
      urothelialcarcinoma. Nephrectomy was analysed in multiple slides of hematoxilin
      eosin and immunohistochemistry. RESULTS: Left nephrectomy was performed. Tumor
      sized 8 cm and showed pathologic findings of epithelioid angiomyolipoma with a
      little component of classic angiomyolipoma. We studied differential diagnosis and
      pathologic characteristics for the prognosis. CONCLUSIONS: Pathologic study in
      detail is fundamental for differential diagnosis and prognosis of this tumor. Our
      patient's pathology showed good prognosis, however follow-up is important due the
      malignant potential of the neoplasm.

PMID- 22971768
TI  - Eosinophilic ureteritis. Report of a case.
AB  - OBJECTIVE: We present the case of a patient with eosinophilic ureteritis.
      METHODS: The patient was admitted with pain on the right renal fossa, and after
      several imaging tests, a mass was found on the right ureter, compatible with
      urothelial neoplasia on the right ureter. RESULTS: Right nephroureterectomy was
      performed and the histopathological diagnosis was eosinophilic ureteritis
      CONCLUSION: Eosinophilic ureteritis is a rare entity with an unclear
      etiology,which is not easily distinguished from urothelial tumours. In the
      differential diagnosis we must take it into account whenever we find a ureteral
      mass associated to eosinophilia.

PMID- 22971769
TI  - Morphological keys in the differential diagnosis of bladder inverted papilloma.
      Study of two types, trabecular and glandular.
AB  - OBJECTIVE: Inverted papilloma of the urinary bladder is an uncommon urothelial
      neoplasm that may be specially difficult to distinguish from urothelial
      carcinoma. METHODS: Two patients with obstructive symptoms and hematuria have
      been studied. In the transurethral resection, accidentally, one showed a
      papillary lesion in the  context of nodular hyperplasia of the prostate, where as
      the other showed a polypoid tumor of the urinary bladder RESULTS: Histologically,
      in both cases, a bladder inverted papilloma was demonstrated, originating from
      the surface transitional epithelium. Basal cells exhibited  peripheral palisading
      pattern in the trabecular form. In the glandular type, Dogiel or umbrella cells
      into the gland-like structures, were recognized.  Immunohistochemical  stains for
      p53 and Ki-67 were negative. Umbrella cells were positive for cytokeratin 20.
      CONCLUSIONS: Two cases of bladder inverted papilloma with relevant morphological
      aspects are presented, which we consider useful for the differential diagnosis
      with  urothelial carcinoma.

PMID- 22971770
TI  - Mixed epithelial and stromal tumor of the kidney (MEST).
AB  - OBJECTIVE: To report an unusual case of renal tumor and review the literature.
      METHODS: We present a 20 years old female with a history of acute right
      pyelonephritis. The ultrasound study revealed a tumor-like image in the lower
      pole  of the right kidney . The CT-scan showed a mixed solid and cystic mass of 7
      cm. in the lower pole of the right kidney. RESULTS: A right laparoscopic partial
      nephrectomy was performed. The total operative time was 90 minutes, with 24
      minutes of warm ischemia. The estimated blood  loss was 50 ml. and the length of
      stay (LOS) 36 hours. The pathology findings confirm a mixed epithelial and
      stromal tumor (MEST) of the kidney. CONCLUSION: Mixed epithelial and stromal
      tumor (MEST) of the kidney is a benign and rare condition that doesn't show a
      clear difference with other renal tumors  in image studies. Nephron-sparing
      surgery with margin study is the standard treatment when is feasible.

PMID- 22971771
TI  - Multinodular polypoid lesion in a non anatomic pit of veromontanum.

PMID- 22971772
TI  - Renal ischemia secondary to retroperitoneal hematoma.

PMID- 22971773
TI  - MicroRNA-29 in the adaptive immune system: setting the threshold.
AB  - Recent research into the role of microRNA (miR) in the immune system has
      identified the miR-29 family as critical regulators of key processes in adaptive
      immunity. The miR-29 family consists of four members with shared regulatory
      capacity, namely miR-29a, miR-29b-1, miR-29b-2 and miR-29c. Being expressed in
      both T and B cells, as well as the main accessory cell types of thymic epithelium
      and dendritic cells, the miR-29 family has been identified as a putative
      regulator of immunity due to the predicted suppression of key immunological
      pathways. The generation of a series of in vivo molecular tools targeting the miR
      29 family has identified the critical role of these miR in setting the molecular
      threshold for three central events in adaptive immunity: (1) control over thymic
      production of T cells by modulating the threshold for infection-associated thymic
      involution, (2) creating a neutral threshold for T cell polarization following
      activation, and (3) setting the threshold for B cell oncogenic transformation.
      These results identify the miR-29 family as potent immune modulators which have
      already been exploited through the evolution of a viral mimic and could
      potentially be exploited further for therapeutic intervention.

PMID- 22971776
TI  - Parenting and Beyond: Common Neurocircuits Underlying Parental and Altruistic
      Caregiving.
AB  - Interpersonal relationships constitute the foundation on which human society is
      based. The infant-caregiver bond is the earliest and most influential of these
      relationships. Driven by evolutionary pressure for survival, parents feel
      compelled to provide care to their biological offspring. However, compassion for
      non-kin is also ubiquitous in human societies, motivating individuals to suppress
      their own self-interests to promote the well-being of non-kin members of the
      society. We argue that the process of early kinship-selective parental care
      provides the foundation for non-exclusive altruism via the activation of a
      general Caregiving System that regulates compassion in any of its forms. We
      propose a tripartite structure of this system that includes (1) the perception of
      need in another, (2) a caring motivational or feeling state, and (3) the delivery
      of a helping response to the individual in need. Findings from human and animal
      research point to specific neurobiological mechanisms including activation of the
      insula and the secretion of oxytocin that support the adaptive functioning of
      this Caregiving System.

PMID- 22971777
TI  - New alkaloids from Lycopodium japonicum.
AB  - Three new alkaloids (1-3), together with ten known alkaloids, were isolated from
      the ethanolic extract of the whole plants of Lycopodium japonicum THUNB. Their
      structures were elucidated on the basis of spectroscopic analysis, including MS
      and NMR methods. All alkaloids isolated were assayed for cytotoxic activity
      against four human cancer cell lines and acetylcholinesterase (AChE) inhibitory
      activity. No alkaloid showed either cytotoxic activity against four human cancer
      cell lines or AChE inhibitory activity.

PMID- 22971778
TI  - Measles virus IgG avidity assay for use in classification of measles vaccine
      failure in measles elimination settings.
AB  - In regions where endemic measles virus has been eliminated, diagnostic assays are
      needed to assist in correctly classifying measles cases irrespective of
      vaccination status. A measles IgG avidity assay was configured using a
      commercially available measles-specific IgG enzyme immunoassay by modifying the
      protocol to include three 5-min washes with diethylamine (60 mM; pH 10.25)
      following serum incubation; serum was serially diluted, and the results were
      expressed as the end titer avidity index. Receiver operating characteristic
      analysis was used for evaluation and validation and to establish low (<=30%) and
      high (>=70%) end titer avidity thresholds. Analysis of 319 serum specimens
      expected to contain either high- or low-avidity antibodies according to clinical
      and epidemiological data indicated that the assay is highly accurate, with an
      area under the curve of 0.998 (95% confidence interval [CI], 0.978 to 1.000),
      sensitivity of 91.9% (95% CI, 83.2% to 97.0%), and specificity of 98.4% (95% CI,
      91.6% to 100%). The assay is rapid (<2 h) and precise (standard deviation [SD],
      4% to 7%). In 18 samples from an elimination setting outbreak, the assay
      identified 2 acute measles cases with low-avidity results; both were IgM-positive
      samples. Additionally, 11 patients (15 samples) with modified measles who were
      found to have high-avidity IgG results were classified as secondary vaccine
      failures; one sample with an intermediate-avidity result was not interpretable.
      In elimination settings, measles IgG avidity assays can complement existing
      diagnostic tools in confirming unvaccinated acute cases and, in conjunction with
      adequate clinical and epidemiologic investigation, aid in the classification of
      vaccine failure cases.

PMID- 22971775
TI  - Genetic visualization of notch signaling in mammalian neurogenesis.
AB  - Notch signaling plays crucial roles in fate determination and the differentiation
      of neural stem cells in embryonic and adult brains. It is now clear that the
      notch pathway is under more complex and dynamic regulation than previously
      thought. To understand the functional details of notch signaling more precisely,
      it is important to reveal when, where, and how notch signaling is dynamically
      communicated between cells, for which the visualization of notch signaling is
      essential. In this review, we introduce recent technical advances in the
      visualization of notch signaling during neural development and in the adult
      brain, and we discuss the physiological significance of dynamic regulation of
      notch signaling.

PMID- 22971779
TI  - Misdiagnosis of late-onset Lyme arthritis by inappropriate use of Borrelia
      burgdorferi immunoblot testing with synovial fluid.
AB  - The primary objective of this study was to determine whether patients with
      putative late-onset Lyme arthritis based upon synovial fluid Borrelia burgdorferi
      IgM and IgG immunoblot testing offered by commercial laboratories satisfied
      conventional criteria for the diagnosis of Lyme arthritis. Secondary objectives
      included assessing the prior duration and responsiveness of associated antibiotic
      therapy. We conducted a retrospective analysis of 11 patients referred to an
      academic medical center infectious disease clinic during the years 2007 to 2009
      with a diagnosis of Lyme disease based upon previously obtained synovial fluid B.
      burgdorferi immunoblot testing. Ten of the 11 (91%) patients with a diagnosis of
      late-onset Lyme arthritis based upon interpretation of synovial fluid B.
      burgdorferi immunoblot testing were seronegative and did not satisfy published
      criteria for the diagnosis of late-onset Lyme arthritis. None of the 10 patients
      had a clinical response to previously received antibiotics despite an average
      course of 72 days. Diagnosis of Lyme arthritis should not be based on synovial
      fluid B. burgdorferi immunoblot testing. This unvalidated test does not appear
      useful for the diagnosis of Lyme disease, and this study reinforces the
      longstanding recommendation to use B. burgdorferi immunoblot testing only on
      serum samples and not other body fluids. Erroneous interpretations of "positive"
      synovial fluid immunoblots may lead to inappropriate antibiotic courses and
      delays in diagnosis of other joint diseases.

PMID- 22971774
TI  - The Eyes Absent proteins in development and disease.
AB  - The Eyes Absent (EYA) proteins, first described in the context of fly eye
      development, are now implicated in processes as disparate as organ development,
      innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer
      metastasis. These functions are associated with an unusual combination of
      biochemical activities: tyrosine phosphatase and threonine phosphatase activities
      in separate domains, and transactivation potential when associated with a DNA
      binding partner. EYA mutations are linked to multiorgan developmental disorders,
      as well as to adult diseases ranging from dilated cardiomyopathy to late-onset
      sensorineural hearing loss. With the growing understanding of EYA biochemical and
      cellular activity, biological function, and association with disease, comes the
      possibility that the EYA proteins are amenable to the design of targeted
      therapeutics. The availability of structural information, direct links to disease
      states, available animal models, and the fact that they utilize unconventional
      reaction mechanisms that could allow specificity, suggest that EYAs are well
      positioned for drug discovery efforts. This review provides a summary of EYA
      structure, activity, and function, as they relate to development and disease,
      with particular emphasis on recent findings.

PMID- 22971780
TI  - HIV-1-specific enzyme-linked immunosorbent spot assay responses in HIV-1-exposed
      uninfected partners in discordant relationships compared to those in low-risk
      controls.
AB  - A number of studies of highly exposed HIV-1-seronegative individuals (HESN) have
      found HIV-1-specific cellular responses. However, there is limited evidence that
      responses prevent infection or are linked to HIV-1 exposure. Peripheral blood
      mononuclear cells (PBMC) were isolated from HESN in HIV-1-discordant
      relationships and low-risk controls in Nairobi, Kenya. HIV-1-specific responses
      were detected using gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot
      (ELISpot) assays stimulated by peptide pools spanning the subtype A HIV-1 genome.
      The HIV-1 incidence in this HESN cohort was 1.5 per 100 person years. Positive
      ELISpot responses were found in 34 (10%) of 331 HESN and 14 (13%) of 107 low-risk
      controls (odds ratio [OR] = 0.76; P = 0.476). The median immunodominant response
      was 18.9 spot-forming units (SFU)/10(6) peripheral blood mononuclear cells
      (PBMC). Among HESN, increasing age (OR = 1.24 per 5 years; P = 0.026) and longer
      cohabitation with the HIV-1-infected partner (OR = 5.88 per 5 years; P = 0.003)
      were associated with responses. These factors were not associated with responses
      in controls. Other exposure indicators, including the partner's HIV-1 load (OR =
      0.99 per log(10) copy/ml; P = 0.974) and CD4 count (OR = 1.09 per 100 cells/MUl;
      P = 0.238), were not associated with responses in HESN. HIV-1-specific cellular
      responses may be less relevant to resistance to infection among HESN who are
      using risk reduction strategies that decrease their direct viral exposure.

PMID- 22971781
TI  - Western blotting is an efficient tool for differential diagnosis of
      paracoccidioidomycosis and pulmonary tuberculosis.
AB  - Sputum and sera from 134 patients screened for tuberculosis (TB) were analyzed to
      investigate TB and paracoccidioidomycosis (PCM). Of these patients, 11 (8.2%)
      were confirmed to have TB, but six (4.5%) were positive only for PCM. All
      patients with PCM presented anti-43-kDa-component antibodies in Western blotting
      (WB) assays, while in the TB-positive patients these antibodies did not appear.
      This preliminary study suggests WB as a potential tool for differential
      laboratory diagnosis between TB and PCM.

PMID- 22971782
TI  - Variability in the distribution of genes encoding virulence factors and putative
      extracellular proteins of Streptococcus pyogenes in India, a region with high
      streptococcal disease burden, and implication for development of a regional
      multisubunit vaccine.
AB  - Streptococcus pyogenes causes a wide variety of human diseases and is a
      significant cause of morbidity and mortality. Attempts to develop a vaccine were
      hampered by the genetic diversity of S. pyogenes across different regions of the
      world. This study sought to identify streptococcal antigens suitable for a region
      specific vaccine in India. We used a two-step approach, first performing
      epidemiological analysis to identify the conserved antigens among Indian
      isolates. The second step consisted of validating the identified antigens by
      serological analysis. The 201 streptococcal clinical isolates from India used in
      this study represented 69 different emm types, with emm12 being the most
      prevalent. Virulence profiling of the North and South Indian S. pyogenes isolates
      with a custom-designed streptococcal virulence microarray identified seven
      conserved putative vaccine candidates. Collagen-like surface protein (SCI),
      putative secreted 5'-nucleotidase (PSNT), and C5a peptidase were found in 100% of
      the isolates, while R28, a putative surface antigen (PSA), and a hypothetical
      protein (HYP) were found in 90% of the isolates. A fibronectin binding protein,
      SfbI, was present in only 78% of the isolates. In order to validate the
      identified potential vaccine candidates, 185 serum samples obtained from patients
      with different clinical manifestations were tested for antibodies. Irrespective
      of clinical manifestations, serum samples showed high antibody titers to all
      proteins except for SCI and R28. Thus, the data indicate that PSNT, C5a
      peptidase, PSA, HYP, and SfbI are promising candidates for a region-specific
      streptococcal vaccine for the different parts of India.

PMID- 22971783
TI  - Two outer membrane lipoproteins from Histophilus somni are immunogenic in rabbits
      and sheep and induce protection against bacterial challenge in mice.
AB  - Histophilus somni is an economically important pathogen of cattle and other
      ruminants and is considered one of the key components of the bovine respiratory
      disease (BRD) complex, the leading cause of economic loss in the livestock
      industry. BRD is a multifactorial syndrome, in which a triad of agents, including
      bacteria, viruses, and predisposing factors or "stressors," combines to induce
      disease. Although vaccines against H. somni have been used for many decades,
      traditional bacterins have failed to demonstrate effective protection in
      vaccinated animals. Hence, the BRD complex continues to produce strong adverse
      effects on the health and well-being of stock and feeder cattle. The generation
      of recombinant proteins may facilitate the development of more effective vaccines
      against H. somni, which could confer better protection against BRD. In the
      present study, primers were designed to amplify, clone, express, and purify two
      recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are
      structural proteins of the outer bacterial membrane. The results presented here
      demonstrate, to our knowledge for the first time, that when formulated, an
      experimental vaccine enriched with these two recombinant lipoproteins generates
      high antibody titers in rabbits and sheep and exerts a protective effect in mice
      against septicemia induced by H. somni bacterial challenge.

PMID- 22971784
TI  - Multimodal treatment of esophageal cancer.
AB  - BACKGROUND: The treatment of localized esophageal cancer has been debated
      controversially over the past decades. Neoadjuvant treatment was used
      empirically, but evidence was limited due to the lack of high-quality
      confirmatory studies. Meanwhile, data have become much clearer due to recently
      published well-conducted randomized controlled trials and meta-analyses. METHODS:
      Neoadjuvant and perioperative platinum fluoropyrimidine-based combination
      chemotherapy has now an established role in the treatment of stage II and stage
      III esophageal adenocarcinoma and cancer of the esophago-gastric junction.
      Neoadjuvant chemoradiation is now the standard of care for treating stage II and
      stage III esophageal squamous cell cancer and can also be considered for treating
      esophageal adenocarcinoma. RESULTS: Patients with esophageal squamous cell cancer
      treated with definitive chemoradiation achieve comparable long-term survival
      compared with surgery. Short-term mortality is less with chemoradiation alone,
      but local tumor control is significantly better with surgery. CONCLUSION: This
      expert review article outlines current data and literature and delineates
      recommendable treatment guidelines for localized esophageal cancer.

PMID- 22971787
TI  - Residual motion and function after glenohumeral or scapulothoracic arthrodesis.
AB  - The purpose of this study was to characterize humerothoracic motion and function
      after glenohumeral or scapulothoracic arthrodesis and to compare those results
      with those from normal shoulders. We evaluated 12 shoulders in 11 patients at an
      average of 71 months after glenohumeral arthrodesis and seven shoulders in six
      patients at an average of 32 months after scapulothoracic arthrodesis. The
      residual motion of the unfused articulation was measured with a spatial position
      sensor. Various activities of daily living and standard clinical range-of-motion
      tests were performed. Nearly all humerothoracic motions were significantly
      decreased in patients after either type of shoulder arthrodesis. Patients with a
      glenohumeral fusion maintained their scapulothoracic motion at levels comparable
      with that of normal subjects. Residual glenohumeral extension and external
      rotation after scapulothoracic fusion were significantly decreased; internal
      rotation remained unchanged compared with motion in subjects with normal
      shoulders. Glenohumeral fusion decreased the patients' ability to perform
      personal care activities requiring extremes of internal rotation or elevation.
      Although glenohumeral arthrodesis limited total humerothoracic motion
      considerably, the majority of patients were improved functionally and were
      relatively free from pain. Most personal care activities were performed
      successfully by all patients with scapulothoracic fusion.

PMID- 22971786
TI  - A 21-day Daniel fast with or without krill oil supplementation improves
      anthropometric parameters and the cardiometabolic profile in men and women.
AB  - BACKGROUND: The Daniel Fast is a vegan diet that prohibits the consumption of
      animal products, refined foods, white flour, preservatives, additives,
      sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21
      days has been demonstrated to improve blood pressure, LDL-C, and certain markers
      of oxidative stress, but it has also been shown to lower HDL-C. Krill oil
      supplementation has been shown to increase HDL-C. METHODS: We investigated the
      effects of following a Daniel Fast dietary plan with either krill oil
      supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for
      21 days. The subjects in this study (12 men and 27 women) were heterogeneous with
      respect to body mass index (BMI) (normal weight, overweight, and obese), blood
      lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting
      glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure
      (normotensive and hypertensive). RESULTS: Krill oil supplementation had no effect
      on any outcome measure (all p > 0.05), and so the data from the krill oil group
      and the placebo group were collapsed and analyzed to examine the effects of
      following a 21-day Daniel Fast. Significant reductions were observed in LDL-C
      (100.6 +/- 4.3 mg/dL vs. 80.0 +/- 3.7 mg/dL), the LDL:HDL ratio (2.0 +/- 0.1 vs.
      1.7 +/- 0.1), fasting blood glucose (101.4 +/- 7.5 mg/dL vs. 91.7 +/- 3.4 mg/dL),
      fasting blood insulin (7.92 +/- 0.80 MUU/mL vs. 5.76 +/- 0.59 MUU/mL),
      homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 +/- 0.30 vs.
      1.40 +/- 0.21), systolic BP (110.7 +/- 2.2 mm Hg vs. 105.5 +/- 1.7 mm Hg), and
      body weight (74.1 +/- 2.4 kg vs. 71.5 +/- 2.3 kg) (all p < 0.05). CONCLUSION:
      Following a Daniel Fast dietary plan improves a variety of cardiometabolic
      parameters in a wide range of individuals in as little as 21 days, and these
      improvements are unaffected by krill oil supplementation. TRIAL REGISTRATION:
      Clinicaltrial.govNCT01378767.

PMID- 22971785
TI  - Molecular pathogenesis of myocardial remodeling and new potential therapeutic
      targets in chronic heart failure.
AB  - It is well known that the natural history of chronic heart failure
      (CHF),regardless of age and aetiology,is characterized by progressive cardiac
      dysfunction refractory to conventional cardiokinetic, diuretic and peripheral
      vasodilator therapy. Several previous studies, both in animals and humans, showed
      that the key pathogenetic element of CHF negative clinical evolution is
      constituted by myocardial remodeling. This is a complex pathologic process of
      ultrastructural rearrangement of the heart induced by various neuro-humoral
      factors released by cardiac fibrocells in response to biomechanical stress
      connected to chronic haemodynamic overload. Typical features of myocardial
      remodeling are represented by cardiomyocytes hypertrophy and apoptosis,
      extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes
      and by cardiac gene expression modifications with fetal genetic program
      reactivation. In the last years, increasing knowledge of subtle molecular and
      cellular mechanisms involved in myocardial remodeling has led to the discovery of
      some new potential therapeutic targets capable of inducing its regression. In
      this paper our attention is focused on the possible use of antiapoptotic and
      antifibrotic agents, and on the fascinating perspectives offered by the
      development of myocardial gene therapy and, in particular, by myocardial
      regenerative therapy.

PMID- 22971788
TI  - Surface replacement of the humeral head in the rheumatoid shoulder.
AB  - The clinical results obtained an average of 4.2 years after resurfacing of the
      humeral head in 72 rheumatoid shoulders showed 94% of the patients being pleased
      regarding pain relief and 82% reporting improved shoulder mobility. Shoulder
      function was significantly improved. The radiographs were analyzed regarding the
      position of the humeral head resurfacing cup, proximal migration of the humerus,
      and glenoid attrition during the follow-up period. Change of the distance between
      the superior margin of the cup and the greater tuberosity and/or change of
      inclination of the prosthesis were regarded as signs of prosthetic loosening.
      With that definition, 25% of the cups were found to be loose at follow-up.
      Prosthetic loosening, however, had no bearing on the clinical result. Also, no
      relationship was found between the position of the cup and the clinical outcome.
      Neither progressive proximal migration of the humerus in 38% of the shoulders nor
      central attrition of the glenoid in 22% of the shoulders showed any relationship
      to gain of mobility, pain relief, or functional ability.

PMID- 22971789
TI  - Humeral head prosthetic arthroplasty: Surgically relevant geometric
      considerations.
AB  - The relationship of the humeral head prosthesis to the humerus is a critical
      determinant of the result in glenohumeral arthroplasty. With canal-fitting
      humeral prostheses, the position of the component is largely dictated by the
      location of the reamed medullary canal. This study explores the geometric
      relationships of a surgically defined humeral reference, the "orthopedic axis."
      This is the axis of a cylindric reamer or press-fit prosthetic stem inserted to
      the appropriate depth for the humeral prosthesis. The orthopedic axis provides a
      reference for measuring surgically important geometric features of the normal
      humeral articular surface and comparing them with those available with humeral
      prosthetic components. In 10 cadaveric proximal humeri, we measured the following
      seven parameters in a radiologic projection of the humerus on the plane
      transverse to the orthopedic axis: the surgically-determined reamed diameter of
      the humeral canal, the diameter of curvature of the humeral head articular
      surface, the effective humeral neck length, the combined head and neck length,
      the subtended angle of the humeral joint surface, the anterior/posterior offset
      of the center of the humeral head, and the biceps-articular surface angle. We
      then determined the prosthetic geometry of a canal-fitting humeral component
      necessary to match the stem size, head diameter, head and neck length, and
      effective humeral neck length. To examine the effect of changing component
      version, we determined the maximal angle of anteversion and retroversion
      achievable by rotation of the component about the orthopedic axis without
      compromising the tuberosities. In the maximal possible anteversion or
      retroversion, the combined head and neck length changed by only 2 mm. Thus the
      effect of component version of a press-fit prosthesis on glenohumeral soft-tissue
      tension is small. The study suggests that the surgeon controls relatively few
      important variables in a canal-fitting humeral arthroplasty. Kinematics of the
      arthroplasty are controlled primarily by soft-tissue releases and the selection
      of the prosthetic head-neck length.

PMID- 22971790
TI  - Anterior and anterior-inferior shoulder instability: Treatment by glenoid labrum
      reconstruction and a modified capsular shift procedure.
AB  - An anterior glenoid labrum reconstruction in conjunction with a modified anterior
      inferior capsular shift is described and was performed in 64 patients (69
      shoulders) with traumatic anterior or anterior-inferior glenohumeral instability.
      Sixty-three operations were performed for recurrent dislocation and six for
      recurrent subluxation. The patients in this study were extremely active in
      sports, with the majority of Tegner ratings exceeding 7.0. Fifty-six patients
      with 61 operated shoulders were available for clinical follow-up at an average of
      36 months (range 28 to 78 months). With rating scales from the American Shoulder
      and Elbow Surgeons, pain improved from an average of 3.1 to an average of 4.4,
      stability improved from 1.1 to 4.5, and function improved from 2.5 to 3.8.
      Postoperative average ranges of motion were 180 degrees  of forward elevation, 72
      degrees  of external rotation with the arm at the side, 92 degrees  of external
      rotation with the arm at 90 degrees  of abduction, and 90 degrees  of internal
      rotation with the arm at 90 degrees  of abduction. Ninety-five percent of the
      patients were satisfied with the procedure. Five patients suffered a recurrent
      dislocation, four from significant trauma. One additional patient experienced an
      episode of subluxation early in the recovery period. According to the criteria of
      Rowe, 90% had excellent or good results.

PMID- 22971791
TI  - Dispelling the fears of plating midclavicular fractures.
AB  - Eighteen midclavicular fractures treated by plate fixation were reviewed at an
      average follow-up of 39 months. The indications for surgery were gross
      displacement and comminution or shortening of greater than 15 mm. The fractures
      united in all cases within 2 to 4 months from the time of operation, without
      significant complications. Many orthopaedic surgeons are reluctant to internally
      fix midclavicular fractures even with gross displacement, citing operative
      treatment as a predisposing factor in the etiology of nonunions. It is now
      appreciated that malunion with shortening of midclavicular fractures, especially
      in young patients, is not benign. We recommend plate fixation for midclavicular
      fractures with gross displacement and comminution or shortening of greater than
      15 mm. It is a safe procedure and does not predispose to nonunion if the
      principles of internal fixation are rigidly followed.

PMID- 22971792
TI  - Snapping scapula: Formation of an erosive, subscapular bursal cyst after partial
      scapulectomy.

PMID- 22971794
TI  - Presidential address: american shoulder and elbow surgeons, eleventh annuel
      meeting vail, colorado, september 10-12, 1992.

PMID- 22971793
TI  - Brachial neuritis after human parvovirus B19 infection.
AB  - This case report presents the clinical picture of a patient with brachial
      neuritis who was investigated and found to have infection with human parvovirus
      B19. The clinical presentations and prevalence of human parvovirus infection are
      discussed, as is the prognosis for brachial neuritis. It is recommended that
      viral serologic testing, including that for human parvovirus, be carried out in
      cases of brachial neuritis. (J Shoulder Elbow Surg 1993;2:321-3).

PMID- 22971795
TI  - Meta-analyses of lightweight versus conventional (heavy weight) mesh in inguinal
      hernia surgery.

PMID- 22971796
TI  - Long-term follow-up after elective adult umbilical hernia repair: low recurrence
      rates also after non-mesh repairs.
AB  - PURPOSE: The purpose of this study was to establish long-term outcome after
      elective adult umbilical hernia (AUH) repair. METHODS: Peri- and postoperative
      data considering all consecutive procedures at our institution during the time
      span from 1999 to 2009 were retrospectively gathered and followed by a
      questionnaire and, if needed, a clinical investigation in early 2011. RESULTS: A
      total of 162 patients (female/male 35 %/65 %) were operated, and 144/162 (89 %)
      answers were gathered, mean follow-up time 70 months; 77 % were sutured, non-mesh
      repairs; 94 % of all AUHs were smaller than 3 cm; and 49 % of the operations were
      performed under local anaesthesia. No perioperative complications were
      encountered. Five postoperative complications were encountered, two serious, both
      after mesh-based repairs. Wound infection rate (SSI) was low, 2/144 (1.4 %).
      7/144 (4.9 %) recurrences were registered, none if mesh-based techniques were
      used, giving a recurrence rate of 6.3 % in suture-based repairs, the difference,
      however, not statistically significant (p = 0.141); 2 % reported persistent pain
      at follow-up, 89 % were overall satisfied with the outcome. CONCLUSIONS: AUH
      repair could be performed with low early and long-term complication rates, with
      low recurrence rates also after non-mesh repairs. A substantial cohort of
      patients will unnecessary be implanted with meshes if mesh-reinforced repairs
      should be used on a routine basis, that is, 16 surplus meshes to prevent one
      recurrence in the present study. We recommend a tailored approach to AUH repair:
      suture-based methods with defects smaller than 2 cm and mesh-based repairs
      considered if larger than that.

PMID- 22971797
TI  - Surveillance for violent deaths--National Violent Death Reporting System, 16
      states, 2009.
AB  - PROBLEM/CONDITION: An estimated 50,000 persons die annually in the United States
      as a result of violence-related injuries. This report summarizes data from CDC's
      National Violent Death Reporting System (NVDRS) regarding violent deaths from 16
      U.S. states for 2009. Results are reported by sex, age group, race/ethnicity,
      marital status, location of injury, method of injury, circumstances of injury,
      and other selected characteristics. REPORTING PERIOD COVERED: 2009. DESCRIPTION
      OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death
      certificates, coroner/medical examiner reports, and law enforcement reports.
      NVDRS data collection began in 2003 with seven states (Alaska, Maryland,
      Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating;
      six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and
      Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in
      2005, and two (Ohio and Michigan) in 2010, for a total of 19 states. This report
      includes data from 16 states that collected statewide data in 2009. California is
      excluded because data were collected in only four counties. Ohio and Michigan are
      excluded because data collection did not begin until 2010. RESULTS: For 2009, a
      total of 15,981 fatal incidents involving 16,418 deaths were captured by NVDRS in
      the 16 states included in this report. The majority (60.6%) of deaths were
      suicides, followed by homicides and deaths involving legal intervention (i.e.,
      deaths caused by police and other persons with legal authority to use deadly
      force, excluding legal executions) (24.7%), deaths of undetermined intent
      (14.2%), and unintentional firearm deaths (0.5%). Suicides occurred at higher
      rates among males, non-Hispanic whites, American Indians/Alaska Natives, and
      persons aged 45-54 years. Suicides occurred most often in a house or apartment
      and involved the use of firearms. Suicides were preceded primarily by mental
      health, intimate partner, or physical health problems or by a crisis during the
      previous 2 weeks. Homicides occurred at higher rates among males and persons aged
      20-24 years; rates were highest among non-Hispanic black males. The majority of
      homicides involved the use of a firearm and occurred in a house or apartment or
      on a street/highway. Homicides were preceded primarily by arguments and
      interpersonal conflicts or in conjunction with another crime. Characteristics
      associated with other manners of death, circumstances preceding death, and
      special populations also are highlighted in this report. INTERPRETATION: This
      report provides a detailed summary of data from NVDRS for 2009. The results
      indicate that violent deaths resulting from self-inflicted or interpersonal
      violence disproportionately affected adults aged <55 years, males, and certain
      racial/ethnic minority populations. For homicides and suicides, relationship
      problems, interpersonal conflicts, mental health problems, and recent crises were
      among the primary factors that might have precipitated the fatal injuries.
      Because additional information might be reported subsequently as participating
      states update their findings, the data provided in this report are preliminary.
      PUBLIC HEALTH ACTION: For the occurrence of violent deaths in the United States
      to be better understood and ultimately prevented, accurate, timely, and
      comprehensive surveillance data are necessary. NVDRS data can be used to monitor
      the occurrence of violence-related fatal injuries and assist public health
      authorities in the development, implementation, and evaluation of programs and
      policies to reduce and prevent violent deaths at the national, state, and local
      levels. The continued development and expansion of NVDRS is essential to CDC's
      efforts to reduce the personal, familial, and societal costs of violence.
      Additional efforts are needed to increase the number of states participating in
      NVDRS, with an ultimate goal of full national representation.

PMID- 22971798
TI  - Regulation of glucose transporter protein-1 and vascular endothelial growth
      factor by hypoxia inducible factor 1alpha under hypoxic conditions in Hep-2 human
      cells.
AB  - The present study evaluated the regulation of glucose transporter protein-1 (Glut
      1) and vascular endothelial growth factor (VEGF) by hypoxia inducible factor
      1alpha (HIF-1alpha) under hypoxic conditions in Hep-2 human cells to explore the
      feasibility of these three genes as tumor markers. Hep-2 cells were cultured
      under hypoxic and normoxic conditions for 6, 12, 24, 36 and 48 h. The
      proliferation of Hep-2 cells was evaluated using an MTT assay. The protein and
      mRNA expression levels of HIF-1alpha, Glut-1 and VEGF were detected using the S-P
      immunocytochemical method, western blotting and reverse transcription polymerase
      chain reaction (RT-PCR). The results revealed that the expression levels of HIF
      1alpha, Glut-1 and VEGF protein in Hep-2 cells were significantly elevated under
      hypoxic conditions compared with those under normoxic conditions over 36 h. Under
      hypoxic conditions, mRNA levels of HIF-1alpha were stable, while mRNA levels of
      Glut-1 and VEGF changed over time. In conclusion, Glut-1 and VEGF were
      upregulated by HIF-1alpha under hypoxic conditions in a time-dependent manner in
      Hep-2 cells and their co-expression serves as a tumor marker.

PMID- 22971800
TI  - Abstracts from the 2012 Annual Scientific Meeting of the BHS.

PMID- 22971799
TI  - A case report concerning male gametes rescued from a Siamese Eld's deer (Rucervus
      eldii siamensis): post-thawed testicular and epididymal sperm quality and
      heterologous zona pellucida binding ability.
AB  - In the present study, the quality of frozen-thawed epididymal and testicular
      sperm recovered from a Siamese Eld's deer was examined. The epididymal sperm
      quality was assessed in fresh, cold-stored at 4 degrees C and frozen-thawed
      samples. Zona binding ability of the frozen-thawed epididymal samples with
      Burmese Eld's deer oocytes was also evaluated. Testicular sperm extracted from
      tissues frozen at -80 or -196 degrees C for one month were examined for membrane
      and DNA integrity. Epididymal sperm retained their quality for up to 24 hr of
      cold storage at 4 degrees C. The percentages of sperm motility, intact membrane,
      intact acrosome and intact DNA were 30, 46.5, 27 and 89.5% in the frozen and
      thawed epididymal sperm, and the average ability to bind with oocytes was 92.5 +/
      64 sperm/oocytes. Around 70% of the sperm extracted from testicular tissues
      cryopreserved at -196 and -80 degrees C for one month showed an intact membrane.
      In conclusion, epididymal and testicular sperm survived for more than 13 hr post
      mortem. Furthermore, cold storage at 4 degrees C and cryopreservation at -196 and
      -80 degrees C maintain the quality of epididymal and testicular sperm. This study
      represents a model for male gamete rescue in endangered Eld's deer.

PMID- 22971802
TI  - Is a woman's preference for chest hair in men influenced by parasite threat?
AB  - Humans (Homo sapiens) are unique primates due to a lack of a thermally insulating
      fur covering, typical of all other primates. Our primary goal was to examine the
      "ectoparasite avoidance mediated by mate choice hypothesis" suggesting that women
      prefer men lacking chest hair in order to avoid ectoparasite loads. We predicted
      that women living in areas with high prevalence of pathogens (n = 161) would be
      less likely to show a preference for a male with chest hair in comparison with
      women living in areas with low pathogen prevalence (n = 183). We found that
      overall preference for man chest hair was low, but there were no significant
      associations between perceived vulnerability to diseases or disgust sensitivity
      and preference of men who have had experimentally removed chest hair. Women who
      lived in an environment with a high parasite prevalence rate (Turkey) showed a
      similar preference for man chest hair as did women from an environment with low
      parasite prevalence (Slovakia). The participants biological fathers' chest hair
      had no significant effect on their preference for men with chest hair. Women
      living in a high-parasite-prevalence environment reported a higher disgust score
      in the sexual domain and more recent experiences with illnesses, suggesting that
      parasites influence sensitivity to sexual disgust. These results provide no
      support for the ectoparasite avoidance hypothesis mediated by mate choice and
      suggest that shaved men bodies are preferred more by women.

PMID- 22971801
TI  - Unwanted sexual experiences in young men: evidence from a survey of university
      students in Chile.
AB  - The public health problem of unwanted sexual experiences (USE) in male youths has
      received little attention. In this study, we examined prevalence of USE, risk
      factors, contexts, and barriers to disclosure with data from a quantitative
      survey of students enrolled in General Education courses at a public university
      in Chile. This study focused on the male sample (N = 466). Approximately 20.4 %
      of participants reported some form of USE since age 14. Forced sex through
      physical coercion, forced sex through verbal coercion or while intoxicated,
      attempted forced sex, and less severe forms of USE were reported by 0.2, 10.1,
      1.4, and 8.7 % of participants, respectively. USE before age 14 was reported by
      9.4 % of participants and was a significant predictor of USE since age 14 (AOR
      6.38, 95 % CI 3.22-12.65, p < .01). The perpetrator of USE since age 14 was most
      commonly identified as a date/partner or friend/acquaintance; other findings on
      contexts and barriers to disclosure were also generally consistent with previous
      results in the literature. In addition, we found substantial co-occurrence of USE
      since age 14 with two other forms of coercion: physical dating violence
      victimization and coerced condom non-use. The study findings indicate a need for
      further attention to these public health problems and have implications for the
      development of violence and HIV/STI prevention programs for adolescent boys and
      young adult men in Chile and elsewhere.

PMID- 22971803
TI  - Caseous mitral annular calcification along the anterolateral annulus causing mild
      mitral regurgitation: multi-modality imaging and diagnosis.

PMID- 22971804
TI  - High performance horizontal gate-all-around silicon nanowire field-effect
      transistors.
AB  - Semiconducting nanowires have been pointed out as one of the most promising
      building blocks for submicron electrical applications. These nanometer materials
      open new opportunities in the area of post-planar traditional metal-oxide
      semiconductor devices. Herein, we demonstrate a new technique to fabricate
      horizontally suspended silicon nanowires with gate-all-around field-effect
      transistors. We present the design, fabrication and electrical measurements of a
      high performance transistor with high on current density (~150 MUA MUm(-1)), high
      on/off current ratio (10(6)), low threshold voltage (~ - 0.4 V), low subthreshold
      slope (~100 mV /dec) and high transconductance (g(m) ~ 9.5 MUS). These high
      performance characteristics were possible due to the tight electrostatic coupling
      of the surrounding gate, which significantly reduced the Schottky-barrier
      effective height, as was confirmed experimentally in this study.

PMID- 22971805
TI  - Refractory ulcer of reconstructed gastric tube after esophagectomy: a case
      report.
AB  - We report a case in which rabeprazole cured gastric tube ulcer after
      esophagectomy for esophageal squamous cell carcinoma (ESCC). A 47-year-old
      Japanese man was referred to our hospital with refractory ulcer of the
      reconstructed gastric tube one year after esophagectomy for ESCC. The ulcer
      proved refractory to healing by the administration of omeprazole or lansoprazole,
      or eradication of Helicobacter pylori after examinations concerning ischemia,
      acid over-secretion and H. pylori infection. Finally, metabolizer type was
      examined for proton pump inhibitors (PPIs), revealing the patient as a hetero
      extensive metabolizer for the CYP2C19 genotype. This suggested sensitivity to
      rabeprazole, but resistance to omeprazole and lansoprazole. The refractory ulcer
      was subsequently cured after changing the PPI to rabeprazole. Examination of PPI
      metabolizer type might thus be important, along with an investigation of
      ischemia, acid secretion and H. pylori infection in the treatment of refractory
      gastric tube ulcer after esophagectomy.

PMID- 22971806
TI  - Radiation-induced synovial sarcoma of the lung diagnosed by gene analysis after
      the surgical resection of chondrosarcoma arising from the scapula.
AB  - The patient was a 62-year-old male who underwent wide resection and radiotherapy
      for right scapular chondrosarcoma 12 years ago. An abnormal shadow was detected
      in the right upper lung field included in the irradiated field on chest X-ray.
      Since the nodule tended to enlarge, a malignant lung tumor was suspected, and
      surgery was performed. On histological examination, spindle cells densely
      proliferated in a bundle pattern. Vimentin, bcl-2 protein, and CD99 were
      positive, and CD34, cytokeratin, AE1/AE3, and EMA were partially positive on
      immunohistochemical staining. The SYT-SSX (synaptotagmin- synovial sarcoma X)
      fusion gene was detected employing RT-PCR, based on which primary synovial
      sarcoma of the lung was diagnosed. The findings also matched the diagnostic
      criteria of radiation-induced sarcoma, suggesting radiation-induced primary
      synovial sarcoma of the lung. Primary synovial sarcoma of the lung is a rare
      tumor. It is difficult to diagnose based on cellular findings, and
      immunohistochemical and genetic investigations are essential. Radiation-induced
      sarcoma may develop through a long-term course, as seen in this patient, for
      which long-term follow-up after radiotherapy is important.

PMID- 22971807
TI  - A stable prostacyclin analogue (iloprost) in the treatment of Buerger's disease:
      a prospective analysis of 150 patients.
AB  - PURPOSE: To assess the efficacy and of iloprost in the treatment of Buerger's
      disease. METHODS: In this prospective study, 158 patients with rest pain and/or
      ischemic ulcers from 17 clinics were administered 1 ng/kg/min intravenous
      iloprost for 28-days. The primary endpoint was complete healing without pain or
      major amputation at 24 weeks. The secondary endpoints were pain assessment,
      reduction in ulcer area, 50% reduction of the ulcer size, shift in the modified
      SVS/ISCVS clinical status grading scale, global assessment by the investigator
      and an independent observer at 4 and 24 weeks. The comparisons were carried out
      with the initial values. The final evaluation was carried out in 150 patients.
      RESULTS: Complete healing rate was significantly better with iloprost treatment
      in comparison to the initial values at 24 weeks (<0.001). The secondary
      endpoints; complete healing rate, pain, the size of the ulcer, 50% reduction of
      the ulcer size, SVS/ISCVS grading scale, assessment by investigator, assessment
      by observer parameters were significantly better at 4 and 24 weeks (<0.001). The
      reduction of the ulcer size was significantly better when comparing 4th and 24th
      week values (<0.05). CONCLUSION: The results of this independent study indicate
      that intravenous iloprost relieves ischemic symptoms efficiently in the acute
      phase Buerger's disease patients. Considering unsatisfactory results following
      surgical revascularisation and sympathectomy in Buerger's disease, prostacyclin
      analogues might be the first line treatment as long as complete abstinence from
      smoking is achieved.

PMID- 22971808
TI  - Replacement of dynamic cultured biograft improves damaged heart function
      comparative study of static cultured biografts-.
AB  - PURPOSE: To determine whether a dynamic cultured biograft can positively affect
      the function of the damaged heart. METHODS: We ligated the coronary artery (LAD)
      of rats to generate a model of myocardial infarction (MI) and then implanted them
      with the following grafts comprising vascular smooth muscle cells (VSMCs) derived
      from the rat aorta and seeded onto biodegradable patches (patch replacement
      therapy; (PRTx)): control without PRTx, PRTx without seeded cells, PRTx with
      static cultured VSMCs, PRTx with dynamic cultured VSMCs and sham-operated.
      Cultured VSMCs were labeled with PKH26 for identification after implantation, and
      the centre of the MI site was excised and replaced with an implanted biograft.
      Cardiac performance was monitored for 12 weeks thereafter and followed by a
      histological study. RESULTS: Although the ejection fraction of the damaged heart
      improved in all groups that were transplanted with grafts, remodeling was
      prevented only in groups with a dynamic or static cultured patch. More cells were
      alpha-SMA-positive in the group with the dynamic, rather than the static cultured
      patch. Cells were positive for PKH26 in the biograft and in the infarcted
      myocardium. CONCLUSIONS: Dynamic cultured biografts improved the function of the
      infarcted myocardium more than statically cultured biografts or those without
      cells.

PMID- 22971809
TI  - Transfemoral versus conventional aortic valve implantation--early postoperative
      cognitive outcome.
AB  - OBJECTIVES: Reduction of cognitive function is a possible side effect after
      cardiac surgery. We investigated the effect of transfemoral versus conventional
      aortic valve replacement on cognitive performance early after surgery. METHODS:
      50 patients with transfemoral, catheter-based aortic valve implantations were
      compared to 50 patients with conventional surgical aortic valve replacement. Six
      neuropsychological subtests from the Syndrom Kurz Test and Alzheimer's Disease
      Assessment Scale were performed preoperatively and on the third postoperative day
      in a double blind fashion. To assess the overall cognitive function and the
      degree of cognitive change across all tests after surgery we combined the six
      test-scores by principal component analysis. RESULTS: The preoperative (Spre), as
      well as postoperative (Spost) overall cognitive function scores, were not
      significantly different between the groups and showed deterioration within both
      groups (Spre conv. 0.2 +/- 1.0 vs Spost conv. -0.6 +/- 1.1, p <0.0005 and Spre
      transfem. -0.2 +/- 1.0 vs Spost transfem. -0.6 +/- 1.1, p = 0.002). This decline
      (Spre -Spost) was not associated with the type of operation (p = 0.1).
      CONCLUSION: Transfemoral aortic valve implantation has no cerebroprotective
      advantage since it leads also to an early postoperative decline of
      neuropsychological abilities, which is comparable to conventional aortic valve
      replacement.

PMID- 22971810
TI  - Determination of oxidative stress and cardiac dysfunction after
      ischemia/reperfusion injury in isolated rat hearts.
AB  - BACKGROUND: Oxidative stress due to reactive oxygen species (ROS) is thought to
      play a considerable role in ischemia/reperfusion (I/R) injury that impairs
      cardiac function. The present study examined oxidative damage in I/R injury and
      investigated the correlation between oxidative stress and impaired cardiac
      function after I/R injury of the isolated rat heart. METHODS: Hearts isolated
      from male Sprague-Dawley rats were mounted on a Langendorff apparatus. Hearts
      arrested using St. Thomas cardioplegic solution and then they were reperfused.
      The hearts were divided into three groups depending on the frequency (0-2) of
      I/R. After I/R, left ventricular developed pressure (LVDP), left ventricular end
      diastolic pressure (LVEDP), positive maximum left ventricular developing pressure
      (max LV dP/dt) and coronary flow (CF) were measured. Creatine kinase (CK) was
      measured in the coronary effluent and 8-hydroxy-2'deoxyguanosine (8OHdG), a
      marker of oxidative DNA damage, was measured. Adenosine triphosphate (ATP) was
      measured from frozen myocardial tissue after experiment. RESULTS: We
      immunohistochemically demonstrated and quantified levels of 8-OHdG after I/R
      injury of the heart. The frequency of I/R injury and cardiac dysfunction
      significantly and negatively correlated. The ATP products were similar among the
      three groups. The incidence of ventricular arrhythmias was not by affected
      oxidative stress. CONCLUSION: The frequency of I/R injury had more of an effect
      on 8-OHdG products and on impaired cardiac function with less myocyte damage than
      ischemic duration within 30 minutes of ischemia.

PMID- 22971811
TI  - Interrelationship and expression profiling of cyclooxygenase and angiogenic
      factors in Indian patients with multiple myeloma.
AB  - Multiple myeloma (MM) is classically illustrated by a desynchronized cytokine
      system with rise in inflammatory cytokines. There are recent reports which
      emphasized the potential role of angiogenesis in the development of MM. Role of
      cyclooxygenase 2 (COX-2) is well documented in the pathogenesis of solid tumors,
      but little is known about its occurrence and function in hematologic neoplasms.
      Involvement of neoangiogenesis is reported in the progression of MM, and
      angiopoietins probably contribute to this progression by enhancing
      neovascularization. Circulatory and mRNA levels of angiogenic factors and
      cyclooxygenase were determined in 125 subjects (75 MM patients and 50 healthy
      controls) by using enzyme-linked immunosorbent assay and quantitative PCR. We
      observed significant increase for angiogenic factors (Ang-1, Ang-2, hepatocyte
      growth factor, and vascular endothelial growth factor) and cyclooxygenase at
      circulatory level, as well as at mRNA level, as compared to healthy controls
      except insignificant increase for Ang-1 at circulatory level. We have also
      observed the significant positive correlation of all angiogenic factors with
      cyclooxygenase. The strong association found between angiogenic factors and COX-2
      in this study may lead to the development of combination therapeutic strategy to
      treat MM. Therefore, targeting COX-2 by using its effective inhibitors
      demonstrating antiangiogenic and antitumor effects could be used as a new
      therapeutic approach for treatment of MM.

PMID- 22971812
TI  - Role and activation time course of phonological and orthographic information
      during phoneme judgments.
AB  - Acquiring literacy establishes connections between the spoken and written system
      and modifies the functioning of the spoken system. As most evidence comes from on
      line speech recognition tasks, it is still a matter of debate when and how these
      two systems interact in metaphonological tasks. The present event-related
      potentials study investigated the role and activation time course of the
      phonological and orthographic representations in an auditory same/different
      phoneme judgment task in which the congruency between phoneme and grapheme was
      orthogonally manipulated. We reported distinct time windows and topographies for
      phonological and orthographic effects. The phonological effect emerged early at
      central and parietal electrode sites and faded away later on, whereas the
      orthographic effect increased progressively, first observable at central and
      parietal sites before generalizing at the frontal site. These effects are clearly
      different from what has been reported in speech recognition tasks and suggest
      that our cognitive system is flexible enough to adjust its functioning to respond
      to the task demands in an optimal way.

PMID- 22971813
TI  - Microfluidic diagnostic tool for the developing world: contactless impedance flow
      cytometry.
AB  - In this work, we demonstrate a novel and cost-effective approach to implement a
      disposable microfluidic contactless impedance cytometer. Conventional methods for
      single cell impedance cytometry use microfabricated electrodes in direct contact
      with the buffer to measure changes of its electrical impedance when cells pass
      through the applied electric field. However, this approach requires expensive
      microfabrication of electrodes, and also, the fabricated electrodes cannot be
      reused without thorough and time-consuming cleaning process. Here, we introduce a
      novel approach to allow for single cell impedance cytometry using electrodes that
      can be reused, without the need for microfabrication of the electrodes. This
      disposable device can be potentially inserted onto a printed circuit board (PCB)
      which has a non-disposable, yet inexpensive, electronic reading apparatus. This
      significantly reduces the manufacturing costs, making it suitable for low
      resource settings, such as point-of-care testing in the developing countries.

PMID- 22971814
TI  - Flexible piezoelectric nanogenerators based on ZnO nanorods grown on common paper
      substrates.
AB  - Nanogenerators capable of harvesting energy from environmental mechanical energy
      are attractive for many applications. In this paper, we present a simple, low
      cost approach to convert low-frequency mechanical energy into electric power
      using piezoelectric ZnO nanorods grown on a common paper substrate. This energy
      conversion device has ultrahigh flexibility and piezoelectric sensitivity and can
      produce an output voltage of up to 10 mV and an output current of about 10 nA. It
      is demonstrated that the device's electric output behavior can be optionally
      changed between four types of mode simply by controlling the straining rate.
      Furthermore, it is also shown that the electric output can be enhanced by scaling
      the size of the device. This energy-harvesting technology provides a simple and
      cost-effective platform to capture low-frequency mechanical energy, such as body
      movements, for practical applications.

PMID- 22971815
TI  - The aging hand and the ergonomics of hearing aid controls.
AB  - OBJECTIVES: The authors investigated the effects of hand function and aging on
      the ability to manipulate different hearing instrument controls. Over the past
      quarter century, hearing aids and hearing aid controls have become increasingly
      miniaturized. It is important to investigate the aging hand and hearing aid
      ergonomics because most hearing aid wearers are adults aged 65 years and above,
      who may have difficulty handling these devices. DESIGN: In Experiment 1, the
      effect of age on the ability to manipulate two different open-fit behind-the-ear
      style hearing aids was investigated by comparing the performance of 20 younger
      (18-25 years of age), 20 young-old (60-70 years of age), and 20 older adults (71
      80 years of age). In Experiment 2, ability to manipulate 11 different hearing
      instrument controls was investigated in 28 older adults who self-reported having
      arthritis in their hand, wrist, or finger and 28 older adults who did not report
      arthritis. For both experiments, the relationship between performance on the
      measures of ability to manipulate the devices and performance on a battery of
      tests to assess hand function was investigated. RESULTS: In Experiment 1, age
      related differences in performance were observed in all the tasks assessing hand
      function and in the tasks assessing ability to manipulate a hearing aid. In
      Experiment 2, although minimal differences were observed between the two groups,
      significant differences were observed depending on the type of hearing instrument
      control. Performance on several of the objective tests of hand function was
      associated with the ability to manipulate hearing instruments. CONCLUSIONS: The
      overall pattern of findings suggest that haptic (touch) sensitivity in the
      fingertips and manual dexterity, as well as disability, pain, and joint stiffness
      of the hand, all contribute to the successful operation of a hearing instrument.
      However, although aging is associated with declining hand function and co
      occurring declines in ability to manipulate a hearing instrument, for the sample
      of individuals in this study, including those who self-reported having arthritis,
      only minimal declines were observed.

PMID- 22971816
TI  - [Appropriate diagnostics in emergency admission. Echocardiography].
AB  - Echocardiography is the central imaging modality for the diagnosis of myocardial,
      valvular and structural heart disease. Coronary artery disease can be detected by
      impaired left ventricular function. The rapid bedside application in unstable
      patients requiring immediate diagnostics and treatment is a decisive advantage of
      echocardiography. The so-called appropriateness criteria propose the use of
      echocardiography in the following emergency situations: (1) assessment of
      patients with hypotension or hemodynamic instability, (2) assessment of patients
      with myocardial ischemia or infarction, (3) evaluation of patients with
      respiratory failure and suspected cardiac origin and (4) application of
      echocardiography in suspected or proven pulmonary embolism for treatment
      decisions. Echocardiography also has an important impact in the differential
      diagnosis of chest pain symptoms. The application of echocardiography in the
      emergency department may set the course for understanding of the underlying
      disease processes as well as the required treatment strategy. Due to the operator
      dependency of the technique, a meaningful application of echocardiography
      requires an experienced investigator even in the emergency department.

PMID- 22971818
TI  - Characterization of a full-length infectious cDNA clone and a GFP reporter
      derivative of the oncolytic picornavirus SVV-001.
AB  - Seneca Valley virus (SVV-001) is an oncolytic picornavirus with selective tropism
      for a subset of human cancers with neuroendocrine differentiation. To
      characterize further the specificity of SVV-001 and its patterns and kinetics of
      intratumoral spread, bacterial plasmids encoding a cDNA clone of the full-length
      wild-type virus and a derivative virus expressing GFP were generated. The full
      length cDNA of the SVV-001 RNA genome was cloned into a bacterial plasmid under
      the control of the T7 core promoter sequence to create an infectious cDNA clone,
      pNTX-09. A GFP reporter virus cDNA clone, pNTX-11, was then generated by cloning
      a fusion protein of GFP and the 2A protein from foot-and-mouth disease virus
      immediately following the native SVV-001 2A sequence. Recombinant GFP-expressing
      reporter virus, SVV-GFP, was rescued from cells transfected with in vitro RNA
      transcripts from pNTX-11 and propagated in cell culture. The proliferation
      kinetics of SVV-001 and SVV-GFP were indistinguishable. The SVV-GFP reporter
      virus was used to determine that a subpopulation of permissive cells is present
      in small-cell lung cancer cell lines previously thought to lack permissivity to
      SVV-001. Finally, it was shown that SVV-GFP administered to tumour-bearing
      animals homes in to and infects tumours whilst having no detectable tropism for
      normal mouse tissues at 1*10(11) viral particles kg(-1), a dose equivalent to
      that administered in ongoing clinical trials. These infectious clones will be of
      substantial value in further characterizing the biology of this virus and as a
      backbone for the generation of additional oncolytic derivatives.

PMID- 22971817
TI  - Phylogenetic viewpoints on regulation of light harvesting and electron transport
      in eukaryotic photosynthetic organisms.
AB  - The comparative study of photosynthetic regulation in the thylakoid membrane of
      different phylogenetic groups can yield valuable insights into mechanisms,
      genetic requirements and redundancy of regulatory processes. This review offers a
      brief summary on the current understanding of light harvesting and photosynthetic
      electron transport regulation in different photosynthetic eukaryotes, with a
      special focus on the comparison between higher plants and unicellular algae of
      secondary endosymbiotic origin. The foundations of thylakoid structure, light
      harvesting, reversible protein phosphorylation and PSI-mediated cyclic electron
      transport are traced not only from green algae to vascular plants but also at the
      branching point between the "green" and the "red" lineage of photosynthetic
      organisms. This approach was particularly valuable in revealing processes that
      (1) are highly conserved between phylogenetic groups, (2) serve a common
      physiological role but nevertheless originate in divergent genetic backgrounds or
      (3) are missing in one phylogenetic branch despite their unequivocal importance
      in another, necessitating a search for alternative regulatory mechanisms and
      interactions.

PMID- 22971820
TI  - Typing of viral hemorrhagic septicemia virus by monoclonal antibodies.
AB  - Seven mAbs with specific reaction patterns against each of the four genotypes and
      eight subtypes of viral hemorrhagic septicemia virus (VHSV) were produced, aiming
      to establish an immunoassay for typing VHSV isolates according to their genotype.
      Among the mAbs, VHS-1.24 reacted with all genotypes except genotype Ie, whilst
      mAb VHS-9.23 reacted with all genotypes except genotype III. mAb VHS-3.80 reacted
      with genotypes Ib, Ic, Id and II. mAb VHS-7.57 reacted with genotypes II and IVa,
      and mAb VHS-5.18 with genotype Ib only. Interestingly, mAb VHS-3.75 reacted with
      all of the genotype III isolates except a rainbow trout-pathogenic isolate from
      the west coast of Norway, and reacted in addition with the IVb isolate, CA-NB00
      01, from the east coast of the USA. Finally, mAb VHS-1.88 reacted with all
      genotype IVb isolates from the Great Lakes, but not with CA-NB00-01. In
      conclusion, we can distinguish between all four genotypes and between five of
      eight subtypes of VHSV by testing isolates in immunoassay using a panel of nine
      mAbs. By Western blotting and transfection of cell cultures, it was shown that
      mAb VHS-1.24 recognized an epitope on the viral phosphoprotein (P), whilst all
      others recognized antigenic determinants on the nucleoprotein (N). From amino
      acid alignments of the various genotypes and subtypes of VHSV isolates, it was
      possible to determine the epitope specificity of mAb VHS-1.24 to be aa 32-34 in
      the P-protein; the specificities of mAbs VHS-3.80, VHS-7.57 and VHS-3.75 were
      found to be aa 43 and 45-48, aa 117 and 121, and aa 103, 118 and 121 of the N
      protein, respectively.

PMID- 22971821
TI  - Significant differences in incubation times in sheep infected with bovine
      spongiform encephalopathy result from variation at codon 141 in the PRNP gene.
AB  - The susceptibility of sheep to prion infection is linked to variation in the PRNP
      gene, which encodes the prion protein. Common polymorphisms occur at codons 136,
      154 and 171. Sheep which are homozygous for the A(136)R(154)Q(171) allele are the
      most susceptible to bovine spongiform encephalopathy (BSE). The effect of other
      polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ
      Cheviot sheep with equal amounts of BSE brain homogenate and a range of
      incubation periods was observed. When we segregated sheep according to the amino
      acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation
      period was observed in LL(141) sheep, whilst incubation periods in FF(141) and
      LF(141) sheep were significantly longer. No statistically significant differences
      existed in the expression of total prion protein or the disease-associated
      isoform in BSE-infected sheep within each genotype subgroup. This suggested that
      the amino acid encoded at codon 141 probably affects incubation times through
      direct effects on protein misfolding rates.

PMID- 22971822
TI  - Two distinct sites are essential for virulent infection and support of variant
      satellite RNA replication in spontaneous beet black scorch virus variants.
AB  - Spontaneous point mutations of virus genomes are important in RNA virus evolution
      and often result in modifications of their biological properties. Spontaneous
      variants of beet black scorch virus (BBSV) and its satellite (sat) RNA were
      generated from cDNA clones by serial propagation in Chenopodium amaranticolor and
      Nicotiana benthamiana. Inoculation with recombinant RNAs synthesized in vitro
      revealed BBSV variants with divergent infectious phenotypes that affected either
      symptom expression or replication of satRNA variants. Sequence alignments showed
      a correlation between the phenotypes and distinct BBSV genomic loci in the 3'UTR
      or in the domain encoding the viral replicase. Comparative analysis between a
      virulent variant, BBSV-m294, and the wild-type (wt) BBSV by site-directed
      mutagenesis indicated that a single-nucleotide substitution of a uridine to a
      guanine at nt 3477 in the 3'UTR was responsible for significant increases in
      viral pathogenicity. Gain-of-function analyses demonstrated that the ability of
      the BBSV variants to support replication of variant satRNAs was mainly determined
      by aa 516 in the P82 replicase. In this case, an arginine substitution for a
      glutamine residue was essential for high levels of replication, and alterations
      of other residues surrounding position 516 in the wtBBSV isolate led to only
      minor phenotypic effects. These results provide evidence that divergence of virus
      functions affecting pathogenicity and supporting parasitic replication can be
      determined by a single genetic site, either a nucleotide or an amino acid. The
      results suggest that complex interactions occur between virus and associated
      satRNAs during virus evolution.

PMID- 22971823
TI  - Novel polyomaviruses in South American bats and their relationship to other
      members of the family Polyomaviridae.
AB  - Bats are the natural reservoir of a variety of viruses, including a polyomavirus
      (PyV) from a North American brown bat. We investigated 163 spleen samples from 22
      bat species from French Guiana for the presence of PyVs. In total, we detected 25
      PyV-positive animals belonging to nine different bat species. Phylogenetic
      analysis was performed on the genomes of eight representative PyVs, and showed
      that the bat PyVs form three distinct lineages within the genus Orthopolyomavirus
      and are genetically different from the previously described North American bat
      virus. Interestingly, two lineages cluster with PyVs found in chimpanzees,
      orangutans and gorillas. In addition, one group of bat PyVs is genetically
      related to the human Merkel cell polyomavirus.

PMID- 22971824
TI  - Recombination profiles between Tomato yellow leaf curl virus and Tomato yellow
      leaf curl Sardinia virus in laboratory and field conditions: evolutionary and
      taxonomic implications.
AB  - Tomato yellow leaf curl Sardinia virus and Tomato yellow leaf curl virus have co
      existed in Italian tomato crops since 2002 and have reached equilibrium, with
      plants hosting molecules of both species plus their recombinants being the most
      frequent case. Recombination events are studied in field samples, as well as in
      experimental co-infections, when recombinants were detected as early as 45 days
      following inoculation. In both conditions, recombination breakpoints were
      essentially absent in regions corresponding to ORFs V2, CP and C4, whereas
      density was highest in the 3'-terminal portion of ORF C3, next to the region
      where the two transcription units co-terminate. The vast majority of breakpoints
      were mapped at antisense ORFs, supporting speculation that the rolling-circle
      replication mechanism, and the existence of sense and antisense ORFs on the
      circular genome, may result in clashes between replication and transcription
      complexes.

PMID- 22971825
TI  - Insertion and recombination events at hypervariable region 1 over 9.6 years of
      hepatitis C virus chronic infection.
AB  - Hepatitis C virus (HCV) exists as a quasispecies within an infected individual.
      We have previously reported an in-frame 3 bp insertion event at the N-terminal
      region of the E2 glycoprotein from a genotype 4a HCV isolate giving rise to an
      atypical 28 aa hypervariable region (HVR) 1. To further explore quasispecies
      evolution at the HVR1, serum samples collected over 9.6 years from the same
      chronically infected, treatment naive individual were subjected to retrospective
      clonal analysis. Uniquely, we observed that isolates containing this atypical
      HVR1 not only persisted for 7.6 years, but dominated the quasispecies swarm. Just
      as striking was the collapse of this population of variants towards the end of
      the sampling period in synchrony with variants containing a classical HVR1 from
      the same lineage. The replication space was subsequently occupied by a second
      minor lineage, which itself was only intermittently detectable at earlier
      sampling points. In conjunction with the observed genetic shift, the coexistence
      of two distinct HVR1 populations facilitated the detection of putative intra
      subtype recombinants, which included the identification of the likely ancestral
      parental donors. Juxtaposed to the considerable plasticity of the HVR1, we also
      document a degree of mutational inflexibility as each of the HVR1 subpopulations
      within our dataset exhibited overall genetic conservation and convergence.
      Finally, we raise the issue of genetic analysis in the context of mixed lineage
      infections.

PMID- 22971826
TI  - Brachypodium distachyon line Bd3-1 resistance is elicited by the barley stripe
      mosaic virus triple gene block 1 movement protein.
AB  - Barley stripe mosaic virus North Dakota 18 (ND18), Beijing (BJ), Xinjiang (XJ),
      Type (TY) and CV21 strains are unable to infect the Brachypodium distachyon Bd3-1
      inbred line, which harbours a resistance gene designated Bsr1, but the Norwich
      (NW) strain is virulent on Bd3-1. Analysis of ND18 and NW genomic RNA
      reassortants and RNAbeta mutants demonstrates that two amino acids within the
      helicase motif of the triple gene block 1 (TGB1) movement protein have major
      effects on their Bd3-1 phenotypes. Resistance to ND18 correlates with an arginine
      residue at TGB1 position 390 (R(390)) and a threonine at position 392 (T(392)),
      whereas the virulent NW strain contains lysines (K) at both positions. ND18 TGB1
      R390K ((ND)TGB1(R390K)) and (ND)TGB1(T392K) single substitutions, and an
      (ND)TGB1(R390K,T392K) double mutation resulted in systemic infections of Bd3-1.
      Reciprocal (ND)TGB1 substitutions into (NW)TGB1 ((NW)TGB1(K390R) and
      (NW)TGB1(K392T)) failed to affect virulence, implying that K(390) and K(392)
      compensate for each other. In contrast, an (NW)TGB1(K390R,K392T) double mutant
      exhibited limited vascular movement in Bd3-1, but developed prominent necrotic
      streaks that spread from secondary leaf veins. This phenotype, combined with the
      appearance of necrotic spots in certain ND18 mutants, and necrosis and rapid
      wilting of Bd3-1 plants after BJ strain ((BJ)TGB1(K390,T392)) inoculations, show
      that Bd3-1 Bsr1 resistance is elicited by the TGB1 protein and suggest that it
      involves a hypersensitive response.

PMID- 22971819
TI  - Estimating reassortment rates in co-circulating Eurasian swine influenza viruses.
AB  - Swine have often been considered as a mixing vessel for different influenza
      strains. In order to assess their role in more detail, we undertook a
      retrospective sequencing study to detect and characterize the reassortants
      present in European swine and to estimate the rate of reassortment between H1N1,
      H1N2 and H3N2 subtypes with Eurasian (avian-like) internal protein-coding
      segments. We analysed 69 newly obtained whole genome sequences of subtypes H1N1
      H3N2 from swine influenza viruses sampled between 1982 and 2008, using Illumina
      and 454 platforms. Analyses of these genomes, together with previously published
      genomes, revealed a large monophyletic clade of Eurasian swine-lineage polymerase
      segments containing H1N1, H1N2 and H3N2 subtypes. We subsequently examined
      reassortments between the haemagglutinin and neuraminidase segments and estimated
      the reassortment rates between lineages using a recently developed evolutionary
      analysis method. High rates of reassortment between H1N2 and H1N1 Eurasian swine
      lineages were detected in European strains, with an average of one reassortment
      every 2-3 years. This rapid reassortment results from co-circulating lineages in
      swine, and in consequence we should expect further reassortments between
      currently circulating swine strains and the recent swine-origin H1N1v pandemic
      strain.

PMID- 22971827
TI  - Furandiones from an endophytic Aspergillus terreus residing in Malus halliana.
AB  - Two new furandiones named asperterone B (1) and C (2) together with four known
      metabolites (3-6) were isolated from the liquid culture of the endophytic fungus
      Aspergillus terreus MHL-P22 residing in the fresh leaves of Malus halliana. The
      structures of the new compounds were elucidated by analysis of their MS, IR, 1D-
      and 2D-NMR spectra. 1 and 2 showed moderate cytotoxic activities against human
      colorectal carcinoma SW1116 cells with IC(50) values of 57.5 and 71.0 uM,
      respectively. The biosynthetic pathway for 1, 2 and their analogues was also
      postulated and briefly discussed.

PMID- 22971828
TI  - Altered regulatory mechanisms governing cell survival in children affected with
      clustering of autoimmune disorders.
AB  - Clustering of Autoimmune Diseases (CAD) is now emerging as a novel clinical
      entity within monogenic immune defects with a high familial occurrence. Aim of
      this study is to evaluate the regulatory mechanisms governing cell survival,
      paying a particular attention to Fas-induced apoptosis, in a cohort of 23
      children affected with CAD. In 14 patients, Fas stimulation failed to induce cell
      apoptosis and in 1 case it was associated with Fas gene mutation. Our study
      highlights the importance to evaluate cell apoptosis in the group of children
      with CAD, which, with this regard, represents a distinct clinical entity.

PMID- 22971829
TI  - Appraisal of conjugated linoleic acid production by probiotic potential of
      Pediococcus spp. GS4.
AB  - Probiotics with ability to produce conjugated linoleic acid (CLA) is considered
      as an additive health benefit property for its known role in colon cancer
      mitigation. The conversion involves the biohydrogenation of the unsaturated fatty
      acid into conjugated form. Probiotic strain Pediococcus spp. GS4 was efficiently
      able to biohydrogenate linoleic acid (LA) into its conjugated form within 48 h of
      incubation. Quantum of CLA produced with a concentration of 121 MUg/ml and
      sustained cell viability of 8.94 log cfu/ml maximally. Moreover, antibacterial
      effect of LA on the strain ability for biohydrogenation was examined at different
      concentrations and concluded to have a direct relationship between LA and amount
      of CLA produced. The efficiency of the strain for CLA production at different pH
      was also estimated and found maximum at pH 6.0 with 149 MUg/ml while this ability
      was reduced at pH 9.0 to 63 MUg/ml. Sesame oil, which is rich in the
      triacylglycerol form of LA, was also found to act as a substrate for CLA
      production by Pediococcus spp. GS4 with the aid of lipase-catalyzed
      triacylglycerol hydrolysis and amount of CLA produced was 31 MUg/ml at 0.2 %
      while 150 MUg/ml at 1.0 % of lipolysed oil in skim milk medium. Conjugated form
      was analyzed using UV scanning, RP-HPLC, and GC-MS. This study also focused on
      the alternative use of lipolysed sesame oil instead of costly LA for
      biohydrogenation and could be a potential source for the industrial production of
      CLA.

PMID- 22971830
TI  - Effect of acetic acid on Saccharomyces carlsbergensis ATCC 6269 batch ethanol
      production monitored by flow cytometry.
AB  - Bioethanol produced from lignocellulosic materials has been considered a
      sustainable alternative fuel. Such type of raw materials have a huge potential,
      but their hydrolysis into mono-sugars releases toxic compounds such as weak
      acids, which affect the microorganisms' physiology, inhibiting the growth and
      ethanol production. Acetic acid (HAc) is the most abundant weak acid in the
      lignocellulosic materials hydrolysates. In order to understand the physiological
      changes of Saccharomyces carlsbergensis when fermenting in the presence of
      different acetic acid (HAc) concentrations, the yeast growth was monitored by
      multi-parameter flow cytometry at same time that the ethanol production was
      assessed. The membrane potential stain DiOC(6)(3) fluorescence intensity
      decreased as the HAc concentration increased, which was attributed to the plasmic
      membrane potential reduction as a result of the toxic effect of the HAc
      undissociated form. Nevertheless, the proportion of cells with permeabilized
      membrane did not increase with the HAc concentration increase. Fermentations
      ending at lower external pH and higher ethanol concentrations depicted the
      highest proportions of permeabilized cells and cells with increased reactive
      oxygen species levels. Flow cytometry allowed monitoring, near real time (at
      line), the physiological states of the yeast during the fermentations. The
      information obtained can be used to optimize culture conditions to improve
      bioethanol production.

PMID- 22971831
TI  - Metal-chelating nanopolymers for antibody purification from human plasma.
AB  - The purification of immunoglobulin G (IgG) from human plasma was performed by
      using a novel metal-chelated adsorbent with nano size. The non-porous
      nanoparticles were produced by surfactant free emulsion polymerization of
      ethylene glycol dimethacrylate (EDMA) and 2-methacryloylamidohistidine (MAH).
      Then, Cu(II) ions were chelated on the nanoparticles. The nano-poly(EDMA-MAH)
      nanoparticles were characterized by Fourier transform infrared, scanning electron
      microscope, atomic force microscope and elemental analysis. The non-porous
      nanoparticles were spherical form and have 100-250 nm size distribution. The
      maximum IgG adsorption capacity of the Cu(II) chelated nanoparticles was found to
      be 463 mg/g polymer at pH 7.0 in HEPES buffer. Desorption of IgG was performed by
      1.0 M NaCl and desorption rate was found to be 97 %. IgG was obtained from human
      plasma with purity of 94 % (up to 578 mg/g polymer). The non-porous nanoparticles
      allowed one-step purification of IgG from human plasma.

PMID- 22971832
TI  - In vitro inhibition effect of some dihydroxy coumarin compounds on purified human
      serum paraoxonase 1 (PON1).
AB  - Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein
      associated, calcium-dependent enzyme that hydrolyses aromatic esters,
      organophosphates and lactones and can protect the low-density lipoprotein against
      oxidation. In this study, in vitro inhibition effect of some dihydroxy coumarin
      compounds namely 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (A), 6,7
      dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (B) and 6,7-dihydroxy-3-(4
      methylphenyl)-2H-chromen-2-one (C) on purified PON1 were investigated by using
      paraoxon as a substrate. PON1 was purified using two-step procedures, namely
      ammonium sulphate precipitation and Sepharose-4B-L-tyrosine-1-naphthylamine
      hydrophobic interaction chromatography. The purified enzyme had a specific
      activity of 11.76 U/mg. The dihydroxy coumarin derivatives of A and B compounds
      inhibited PON1 enzyme activity in a noncompetitive inhibition manner with K(i) of
      0.0080+/-0.256 and 0.0003+/-0.018 mM values, respectively. C compound exerted an
      uncompetitive inhibition of PON1 enzyme activity with K(i) of 0.0010+/-0.173 mM.
      Moreover, dihydroxy coumarin derivatives of A, B and C compounds were effective
      inhibitors on purified human serum PON1 activity with IC(50) of 0.012, 0.022 and
      0.003 mM values, respectively. IC(50) value of unsubstituted 6,7 dihydroxy
      coumarin was found as 0.178 mM. The present study has demonstrated that PON1
      activity is very highly sensitive to studied coumarin derivatives.

PMID- 22971833
TI  - Development and characterization of microsatellite markers (SSR) in Sesamum
      (Sesamum indicum L.) species.
AB  - Microsatellites, also known as simple sequence repeats (SSRs), are the class of
      repetitive DNA sequences present throughout the genome of many plant and animal
      species. Recent advances in molecular genetics had been the introduction of
      microsatellite markers to investigate the genetic structuring of natural plant
      populations. We have employed an enrichment strategy for microsatellite isolation
      by using multi-enzymes digestion, microsatellite oligoprobes, and streptavidin
      magnetic beads in Sesamum (Sesamum indicum L.). More than 200 SSR motifs were
      detected (SSR motifs >=2 repeat units or 6 bp); 80 % of the clones contained SSR
      motifs. When regarding SSRs with four or more repeat units and a minimum length
      of 10 bp, 132 of them showed repeats. Eighteen SSR markers were initially
      characterized for optimum annealing temperature using a gradient PCR technique.
      Among the 18 SSR markers characterized, five were found to be polymorphic and
      used to analyze 60 Sesamum germplasm accessions. The maximum number of alleles
      detected was four with a single primer and the least number of two alleles with
      three primers with an average PIC value of 0.77. SSRs are a valuable tool for
      estimating genetic diversity and analyzing the evolutionary and historical
      development of cultivars at the genomic level in sesame breeding programs.

PMID- 22971834
TI  - Influence of biofilm density on anaerobic sequencing batch biofilm reactor
      treating mustard tuber wastewater.
AB  - Considering the characteristics of high salinity, high concentration of organic
      matter, and high biodegradability, a new and efficient anaerobic sequencing batch
      biofilm reactor (ASBBR) was chosen as an anaerobic pretreatment unit to treat
      most organic compounds in mustard tuber wastewater. By changing the biofilm
      density of the reactor, the test was carried out to find out the influence of
      biofilm density on effluent COD, the content of the sludge dehydrogenase, and gas
      production rate. Results showed that under the condition of 30  degrees C,
      draining ratio of 1/3, and 2 days of hydraulic retention time, COD removal rate
      increased from 71.5 to 90.5 % when the biofilm density increased from 15 to 50 %;
      however, COD removal rate increased from 90.5 to 91.3 % when the biofilm density
      increased from 50 to 70 %. According to the influence of biofilm density on
      effluent COD, the content of the sludge dehydrogenase, and gas production rate,
      ASBBR should take 50 % biofilm density in mustard wastewater treatment. At the
      same time, these design parameters can be used to guide practical engineering.

PMID- 22971835
TI  - Saliva metabolomics opens door to biomarker discovery, disease diagnosis, and
      treatment.
AB  - Metabolomics is the systematic study of the unique chemical fingerprints of low
      molecular weight endogenous metabolites or metabolite profiles in a biological
      sample. Metabolites that are important indicators of physiological or
      pathological states can provide information for the identification of early and
      differential markers for disease and help to understand its occurrence and
      progression. Analysis of these key biomarkers has become an important role to
      monitor the state of biological organisms and is a widely used diagnostic tool
      for disease. Metabolomic analyses are propelling the field of medical diagnostics
      forward at unprecedented rates because of its ability to reliably identify
      metabolites that are at the metabolic level in concentration. These advancements
      have benefited biomarker research to the point where saliva is now recognized as
      an excellent diagnostic medium for the detection of disease. Saliva contains a
      large array of metabolites, many of which can be informative for the detection of
      diseases. Salivary diagnostics offer an easy, inexpensive, safe, and noninvasive
      approach for disease detection. Discovery of salivary biomarkers that could be
      used to scrutinize health and disease surveillance has addressed its diagnostic
      value for clinical applications. Availability of emerging metabolomic techniques
      gives optimism that saliva can eventually be placed as a biomedium for clinical
      diagnostics. Comprehensive salivary metabolome will be an important resource for
      researchers who are studying metabolite chemistry, especially in the fields of
      salivary diagnostics, and will be helpful for analyzing and hence identifying
      corresponding disease-related salivary biomarkers. This review presents an
      overview of the value of saliva as a credible diagnostic tool, the discovery of
      salivary biomarkers, and the development of salivary diagnostics now and in the
      future. In particular, proof of principle has been demonstrated for salivary
      biomarker research.

PMID- 22971836
TI  - New carbosilane polymers with interacting ferrocenes as support and
      bioelectrocatalysts of oxidases to develop versatile and specific amperometric
      biodevices.
AB  - In this work, the bioelectrocatalytical properties and kinetic characteristics of
      new oxidase amperometric biosensors based on two different ferrocene
      functionalized carbosilane polymers, polydiallylmethylsilane (PDAMS) and
      polymethyldiundecenylsilane (PMDUS) are described. In the development of these
      biodevices, glucose oxidase has been used as example of oxidase enzyme, and two
      different immobilization procedures have been studied. The polymer-modified
      electrodes act as efficient transducers for glucose sensing in anodic and
      cathodic aerobic conditions and also in anodic anaerobic conditions, and this
      fact turns them into useful devices for a wide field of applications. PMDUS has
      shown to be the bioelectrocatalyst with best kinetic and analytical properties in
      aerobic media while PDAMS was better in anaerobic conditions. The best aerobic
      biosensor developed displayed a strictly linear range from 0 to 3.0 mM, a
      detection limit of 7.8 MUM and a response time less than 2 s in an ascorbate
      interference free work potential interval. The apparent Michaelis-Menten constant
      was calculated to be 1.36 mM according to the Lineweaver-Burk equation.

PMID- 22971838
TI  - The Salvia miltiorrhiza monomer IH764-3 induces apoptosis of hepatic stellate
      cells in vivo in a bile duct ligation-induced model of liver fibrosis.
AB  - During the process of liver fibrosis, hepatic stellate cells (HSCs) play a
      critical role in the excessive production of extracellular matrix (ECM). Previous
      studies have indicated that the monomer IH764-3, one of the major bioactive
      components of Salvia miltiorrhiza, is able to inhibit HSC proliferation and
      induce the apoptosis of activated HSCs in vitro. In the current study, we used a
      rat model of liver fibrosis induced by bile duct ligation (BDL) to investigate
      the effect of the monomer IH764-3 on the induction of apoptosis in HSCs in vivo.
      The rat model of liver fibrosis was established by BDL. Immunohistochemical
      staining of alpha-smooth muscle actin (alpha-SMA) was performed to detect HSC
      activation and proliferation and HSC apoptosis was detected by terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and alpha-SMA
      immunohistochemical double staining. In addition, the protein expression levels
      of focal adhesion kinase (FAK), p-FAK (Tyr397), extracellular signal-regulated
      kinase (ERK) and p-ERK and the mRNA expression levels of FAK and ERK were
      measured by western blotting and reverse transcription-polymerase chain reaction
      (RT-PCR), respectively. The monomer IH764-3 was associated with a significant
      decrease in intrahepatic fibrogenesis and collagen deposition and attenuated the
      liver fibrosis induced by BDL. Immunohistochemical staining revealed that the
      expression of alpha-SMA in the IH764-3 group was significantly decreased compared
      with that in the model group (12.92+/-2.45 vs. 22.65+/-2.16%, P<0.01). TUNEL and
      alpha-SMA immunohistochemical double staining also confirmed that IH764-3
      increased the apoptotic rate of the activated HSCs (34.8+/-4.5 vs. 4.72+/-0.37%,
      P<0.01). Moreover, the results revealed that IH764-3 downregulated the expression
      levels of FAK, p-FAK (Tyr397), ERK and p-ERK in the liver tissue of rats with
      liver fibrosis. The monomer IH764-3 ameliorates experimental liver fibrosis by
      inhibiting HSC proliferation and inducing HSC apoptosis, warranting its use as a
      potential therapeutic agent in the treatment of liver fibrosis.

PMID- 22971837
TI  - A cannabigerol quinone alleviates neuroinflammation in a chronic model of
      multiple sclerosis.
AB  - Phytocannabinoids like ?(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show
      a beneficial effect on neuroinflammatory and neurodegenerative processes through
      cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms.
      Natural and synthetic cannabinoids also target the nuclear receptor peroxisome
      proliferator-activated receptor-gamma (PPARgamma), an attractive molecular target
      for the treatment of neuroinflammation. As part of a study on the SAR of
      phytocannabinoids, we have investigated the effect of the oxidation modification
      in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) and PPARgamma
      binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti
      inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity,
      activated PPARgamma transcriptional activity and inhibited the release of pro
      inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine
      encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to
      investigate the anti-inflammatory activity of this compound in vivo. Motor
      function performance was evaluated and the neuroinflammatory response and gene
      expression pattern in brain and spinal cord were studied by immunostaining and
      qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV
      infection, decreased microglia reactivity and modulated the expression of genes
      involved in MS pathophysiology. These data lead us to consider VCE-003 to have
      high potential for drug development against MS and perhaps other
      neuroinflammatory diseases.

PMID- 22971840
TI  - Rule learning by zebra finches in an artificial grammar learning task: which
      rule?
AB  - A hallmark of the human language faculty is the use of syntactic rules. The
      natural vocalizations of animals are syntactically simple, but several studies
      indicate that animals can detect and discriminate more complex structures in
      acoustic stimuli. However, how they discriminate such structures is often not
      clear. Using an artificial grammar learning paradigm, zebra finches were tested
      in a Go/No-go experiment for their ability to distinguish structurally different
      three-element sound sequences. In Experiment 1, zebra finches learned to
      discriminate ABA and BAB from ABB, AAB, BBA, and ABB sequences. Tests with probe
      sounds consisting of four elements suggested that the discrimination was based on
      attending to the presence or absence of repeated A- and B-elements. One bird
      generalized the discrimination to a new element type. In Experiment 2, we
      continued the training by adding four-element songs following a 'first and last
      identical versus different' rule that could not be solved by attending to
      repetitions. Only two out of five birds learned the overall discrimination.
      Testing with novel probes demonstrated that discrimination was not based on using
      the 'first and last identical' rule, but on attending to the presence or absence
      of the individual training stimuli. The two birds differed in the strategies
      used. Our results thus demonstrate only a limited degree of abstract rule
      learning but highlight the need for extensive and critical probe testing to
      examine the rules that animals (and humans) use to solve artificial grammar
      learning tasks. They also underline that rule learning strategies may differ
      between individuals.

PMID- 22971841
TI  - Persistent electrical scar in the atrium evaluated on voltage mapping with a
      CARTO system in suspected acute myocarditis.

PMID- 22971839
TI  - Sample preparation of Mycobacterium tuberculosis extracts for nuclear magnetic
      resonance metabolomic studies.
AB  - Mycobacterium tuberculosis is a major cause of mortality in human beings on a
      global scale. The emergence of both multi- (MDR) and extensively-(XDR) drug
      resistant strains threatens to derail current disease control efforts. Thus,
      there is an urgent need to develop drugs and vaccines that are more effective
      than those currently available. The genome of M. tuberculosis has been known for
      more than 10 years, yet there are important gaps in our knowledge of gene
      function and essentiality. Many studies have since used gene expression analysis
      at both the transcriptomic and proteomic levels to determine the effects of
      drugs, oxidants, and growth conditions on the global patterns of gene expression.
      Ultimately, the final response of these changes is reflected in the metabolic
      composition of the bacterium including a few thousand small molecular weight
      chemicals. Comparing the metabolic profiles of wild type and mutant strains,
      either untreated or treated with a particular drug, can effectively allow target
      identification and may lead to the development of novel inhibitors with anti
      tubercular activity. Likewise, the effects of two or more conditions on the
      metabolome can also be assessed. Nuclear magnetic resonance (NMR) is a powerful
      technology that is used to identify and quantify metabolic intermediates. In this
      protocol, procedures for the preparation of M. tuberculosis cell extracts for NMR
      metabolomic analysis are described. Cell cultures are grown under appropriate
      conditions and required Biosafety Level 3 containment, harvested, and subjected
      to mechanical lysis while maintaining cold temperatures to maximize preservation
      of metabolites. Cell lysates are recovered, filtered sterilized, and stored at
      ultra-low temperatures. Aliquots from these cell extracts are plated on
      Middlebrook 7H9 agar for colony-forming units to verify absence of viable cells.
      Upon two months of incubation at 37  degrees C, if no viable colonies are
      observed, samples are removed from the containment facility for downstream
      processing. Extracts are lyophilized, resuspended in deuterated buffer and
      injected in the NMR instrument, capturing spectroscopic data that is then
      subjected to statistical analysis. The procedures described can be applied for
      both one-dimensional (1D) H NMR and two-dimensional (2D) H-(13)C NMR analyses.
      This methodology provides more reliable small molecular weight metabolite
      identification and more reliable and sensitive quantitative analyses of cell
      extract metabolic compositions than chromatographic methods. Variations of the
      procedure described following the cell lysis step can also be adapted for
      parallel proteomic analysis.

PMID- 22971842
TI  - Peri-atrial epicardial adipose tissue is associated with new-onset nonvalvular
      atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with considerable morbidity
      and mortality in patients with coronary artery disease (CAD). Epicardial adipose
      tissue (EAT) is recognized as an important inflammatory tissue that may exert
      deleterious effects on the adjacent left atrial (LA) wall. Multidetector computed
      tomography (MDCT) can accurately assess EAT's volume and distribution. This study
      used MDCT to investigate the effect of peri-atrial EAT on new-onset nonvalvular
      AF. METHODS AND RESULTS: The study group consisted of 279 patients (176 men; age,
      65+/-10 years) with no history of AF who underwent MDCT examination for
      evaluation of CAD. EAT was automatically identified on the basis of threshold
      attenuation values of -30 to -250 Hounsfield units. EAT volume was calculated as
      the sum of EAT area and subsequently divided into peri-atrial and peri
      ventricular EAT. During follow-up of 3.3+/-1.0 years, AF occurred in 17 (6.1%)
      patients. Cox proportional hazards regression analysis indicated that male sex,
      and the LA and peri-atrial EAT volumes (P=0.03, P<0.001, and P<0.001,
      respectively) were independent predictors for future AF. The sensitivity and
      specificity for the prediction of AF using a peri-atrial EAT volume index of >=27
      ml/m(2) were 88% and 92%, respectively. CONCLUSIONS: This is the first study
      demonstrating that peri-atrial EAT volume estimated by MDCT excellently predicted
      the development of new-onset AF in patients with CAD, independent of LA
      enlargement.

PMID- 22971843
TI  - Inhibitory effect of cibenzoline on Na+/Ca2+ exchange current in guinea-pig
      cardiac ventricular myocytes.
AB  - The effect of cibenzoline, a class I antiarrhythmic drug, on Na(+)/Ca(2+)
      exchange current (I(NCX)) was investigated using the patch-clamp method.
      Cibenzoline inhibited the bi-directional I(NCX) in a concentration-dependent
      manner. The IC(50) values of cibenzoline for the outward and inward components of
      I(NCX) were 77 and 84 MUM, respectively, with Hill coefficients of 1.
      Intracellular application of trypsin via the pipette solution did not change the
      inhibitory effect of cibenzoline. The inhibitory effect of cibenzoline on I(NCX)
      at pH(o) 6.5 was smaller than those at pH(o) 7.4 and pH(o) 8.2. We conclude that
      cibenzoline inhibits I(NCX) in supra-therapeutic concentrations.

PMID- 22971844
TI  - Methylglyoxal accumulation in arterial walls causes vascular contractile
      dysfunction in spontaneously hypertensive rats.
AB  - Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetes
      related macrovascular complications including hypertension. In the present study,
      we examined if MGO accumulation affects vascular reactivity of isolated
      mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR
      were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG
      partially normalized increased blood pressure in SHR. In mesenteric artery from
      SHR treated with AG, increased accumulation of MGO-derived advanced glycation end
      products was reversed. In mesenteric artery from SHR, AG normalized impaired
      acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced
      contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric
      artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase (NOX) inhibitor augmented ACh-induced relaxation. Protein
      expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric
      artery, which was normalized by AG. Acute treatment with an AT2R blocker but not
      a NOX inhibitor normalized the increased Ang II-induced contraction in SHR
      mesenteric artery. The present results demonstrate that MGO accumulation in
      mesenteric artery may mediate development of hypertension in SHR at least in part
      via increased ROS-mediated impairment of endothelium-dependent relaxation and
      AT2R-mediated increased Ang II contraction.

PMID- 22971845
TI  - Antidiabetic effects of SGLT2-selective inhibitor ipragliflozin in streptozotocin
      nicotinamide-induced mildly diabetic mice.
AB  - Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose
      reabsorption, and inhibition of renal SGLT2 activity represents an innovative
      strategy for the treatment of hyperglycemia in diabetic patients. The present
      study investigated the antidiabetic effects of ipragliflozin, a SGLT2-selective
      inhibitor, in streptozotocin-nicotinamide-induced mildly diabetic mice, which
      exhibited a mild decline in glucose tolerance associated with the loss of early
      phase insulin secretion. Oral administration of ipragliflozin increased urinary
      glucose excretion in a dose-dependent manner, an effect which was significant at
      doses of 0.3 mg/kg or higher and lasted over 12 h. In addition, ipragliflozin
      dose-dependently improved hyperglycemia and glucose intolerance with concomitant
      decreases in plasma insulin levels without causing hypoglycemia. Once-daily
      dosing of ipragliflozin (0.1 - 3 mg/kg) for 4 weeks attenuated hyperglycemia,
      glucose intolerance, and impaired insulin secretion. These results suggest that
      the SGLT2-selective inhibitor ipragliflozin increases urinary glucose excretion
      by inhibiting renal glucose reabsorption, improves hyperglycemia in
      streptozotocin-nicotinamide-induced mildly diabetic mice, and may be useful for
      treating type 2 diabetes.

PMID- 22971846
TI  - Involvement of the endocannabinoid system in ethanol-induced corticostriatal
      synaptic depression.
AB  - Ethanol is a wildly abused substance that causes various problems and damage in
      our society. We examined the connection between the action of ethanol and the
      endocannabinoid system in corticostriatal synaptic transmission by recording
      excitatory post-synaptic currents (EPSCs). Acute treatment of ethanol (100 mM)
      inhibited corticostriatal EPSCs. In the presence of AM 251 (5 MUM), a cannabinoid
      1 (CB(1))-receptor antagonist, or AM 404 (5 MUM), a cannabinoid transporter
      inhibitor, the inhibition of corticostriatal EPSCs caused by ethanol was
      significantly reduced. This result suggests the possibility that the
      endocannabinoid system is involved in the action of ethanol. To support this
      result, brain slices were pre-treated with WIN 55,212-2 (1 MUM), a CB(1)-receptor
      agonist, following treatment of ethanol or treated with WIN 55,212-2 alone. There
      was no significant difference between each other, indicating that when CB(1)
      receptors are previously activated, the effect of ethanol is blunted. These
      results suggest that the activation of the endocannabinoid system is one of the
      possible mechanisms involved in ethanol-induced corticostriatal synaptic
      depression.

PMID- 22971847
TI  - A new method for evaluation of motivational effects of drugs.
AB  - Motivation is a process that continuously changes behavior to achieve a goal and
      can be conceptualized as a series of steps relating to that process. Intracranial
      self-stimulation (ICSS) behavior is considered to consist of reward and
      motivational effects. Moreover, priming stimulation of ICSS behavior is known to
      promote motivational effects. Using the runway method and priming stimulation,
      rewards and motivational effects of ICSS behavior can be differentiated. We
      investigated whether the runway method and priming stimulation of ICSS behavior
      could be used to evaluate motivational effects of a drug. In the ICSS runway
      model, running speed was considered as a reference of motivational effect. An
      assessment of pharmacological drugs known to influence motivational states was
      also undertaken. Using our experimental methods, prominent changes were observed
      in running speed when animals were administered methamphetamine and nicotine.
      Based on our results, we conclude that the runway method may be useful for the
      evaluation of substances that affect motivation. This review introduces 4 types
      of neuronal processes involved in motivation, reward mechanisms, outlines
      evaluation methods, and describes motivational properties of psychoactive drugs.

PMID- 22971848
TI  - Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo
      epidermal skin substitutes.
AB  - Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat
      gland cells can develop a multilayered epidermis. The question still remains
      whether these cells can fulfill exclusive and very specific functional properties
      of epidermal keratinocytes, such as the incorporation of melanin, a feature
      absent in sweat gland cells. We added human melanocytes to eccrine sweat gland
      cells to let them develop into an epidermal analog in vivo. The interaction
      between melanocytes and sweat gland-derived keratinocytes was investigated. The
      following results were gained: (1) macroscopically, a pigmentation of the
      substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the
      development of a multilayered, stratified epidermis with melanocytes distributed
      evenly throughout the basal layer; (3) melanocytic dendrites projected to
      suprabasal layers; and (4) melanin was observed to be integrated into former
      eccrine sweat gland cells. These skin substitutes were similar or equal to skin
      substitutes cultured from human epidermal keratinocytes. The only differences
      observed were a delay in pigmentation and less melanin uptake. These data suggest
      that eccrine sweat gland cells can form a functional epidermal melanin unit,
      thereby providing striking evidence that they can assume one of the most
      characteristic keratinocyte properties.

PMID- 22971849
TI  - Examining youth and program predictors of engagement in out-of-school time
      programs.
AB  - Prior research suggests that youths' engagement in out-of-school time programs
      may be a crucial factor linking program participation to positive outcomes during
      adolescence. Guided by the theoretical concept of flow and by stage-environment
      fit theory, the present study explored correlates of engagement in youth
      programs. Engagement was conceptualized as the extent to which youth found the
      program activities enjoyable, interesting, and challenging. The current study
      examined how program content, monetary incentives, and youth demographic
      characteristics were linked to youth engagement among a sample of primarily low
      income middle and high school youth attending 30 out-of-school programs (n = 435,
      51 % female). Results from multilevel models suggested that program content and
      staff quality were strongly associated with youth engagement. Youth who reported
      learning new skills, learning about college, and learning about jobs through
      activities in the program were more engaged, as were youth who found the staff
      caring and competent. Results demonstrated that the link between learning content
      for the future and engagement was stronger for older youth than younger youth. In
      addition, there was a trend suggesting that providing a monetary incentive was
      associated negatively with youth engagement. Taken as a whole, these findings
      have important implications for researchers, practitioners, and policymakers
      interested in understanding the characteristics of out-of-school time programs
      that engage older youth.

PMID- 22971850
TI  - The Stoppa approach for acetabular fracture.
AB  - OBJECTIVE: Acetabular fractures pose a great surgical challenge for orthopedic
      trauma surgeons. We believe that the Stoppa approach with an iliac window
      extension, previously described as a modified Stoppa approach is adequate for the
      majority of acetabular fractures excluding those with predominant posterior wall
      involvement. In this paper we will present our experience in using the Stoppa
      approach, its indications, preparations, the detailed surgical approach,
      complications and the different tips used in this relatively modern approach.
      INDICATIONS: All simple and combined fracture types that involve the anterior
      column of the pelvis including the quadrilateral plate. CONTRAINDICATIONS:
      Posterior wall or extensive posterior column involvement. Transverse and T
      fractures with mainly posterior displacement. SURGICAL TECHNIQUE: Suprapubic,
      intrapelvic approach, extending from the symphysis pubis anteriorly to the
      sacroiliac joint posteriorly. Superficial landmarks are identical to the
      Pfannenstiel approach, the rectus abdominis muscles are longitudinally dissected,
      the symphysis pubis is exposed and a sub-periosteal deep surgical dissection is
      carried out along the anterior column and the quadrilateral plate, and
      posteriorly toward the greater sciatic notch and the sacroiliac joint. RESULTS:
      In a 5-year review of 60 acetabular fractures that underwent open reduction and
      internal fixation using the modified Stoppa approach, there were 36% anterior
      column fractures, 28% both-column fractures, the rest being anterior column with
      posterior hemi transverse fractures, transverse and T-fractures. Any extension of
      the fracture to the iliac wing necessitated an additional lateral window (93% of
      cases). In cases with posterior displacement, an additional approach was utilized
      to address a posterior wall fracture. All fractures healed within 12 weeks. Mean
      Merle d'Aubigne score was 15.22. Postoperative radiological evaluation revealed
      anatomical reduction in 54% of the patients, satisfactory in 43%, and
      unsatisfactory in 3% of the patients. Overall there were 15 minor and major
      complications.

PMID- 22971851
TI  - Leprosy:before and after elimination from Nepal.

PMID- 22971852
TI  - Prevalence of intestinal parasitosis among school children in Baglung districts
      of Western Nepal.
AB  - BACKGROUND: This study was carried out to estimate the prevalence of intestinal
      parasites among school-going children of the Baglung municipality from December
      2010 to January 2011. OBJECTIVE: To find out prevalence of parasitosis among
      school aged children and to make necessary recommendations for preventive
      measures. METHOD: A total of 260 stool samples were collected. A structured
      questionnaire was used to collect data on predisposing factors. Nails were
      observed without prior information to the subjects so as to find their hygienic
      practice. The stool samples were examined by direct wet mount and formal ether
      concentration technique. RESULTS: The total prevalence of the intestinal
      parasitosis was found to be 21.05%. The prevalence for individual parasites was
      as follows: Entamoeba histolytica (9.23%), Giardia lamblia (5.76%), Trichuris
      trichuria (5%), Ancylostoma duodenale (2.65%) and Ascaris lumbricoides (2.3%).
      Nail hygiene and level of education were significantly associated with intestinal
      parasitosis. The gender and age of the children, sanitary habits including toilet
      use, hand washing practice, and the use of the antihelminthic drug (albendazole)
      were not significantly associated with intestinal parasitosis. Higher prevalence
      was seen in boys, children belonging to age group 10-14 years, lower secondary
      students, among those who reported gastrointestinal problems within last six
      months, children from agriculture-based families and children with untrimmed
      nail. CONCLUSION: Major contributors for the prevalence of parasites were found
      to be poor personal hygiene and educational level of the children. Health
      education and mass treatment are recommended as a preventive measures.

PMID- 22971853
TI  - Prognostic value of rapid test for diagnosis of dengue in Nepalese patients
      during 2010 epidemic.
AB  - BACKGROUND: Dengue is an emerging vector borne disease in Nepal and rapid
      diagnostic test is important for early diagnosis of the disease. OBJECTIVES: The
      aim of the study was to evaluate the diagnostic accuracy of commonly used rapid
      immunochromatographic test kit in Nepal during 2010 dengue epidemic and to assess
      disease burden of dengue. METHODS: A total of 131 acute and nonacute serum
      samples were collected during recent epidemic of dengue in 2010 from clinically
      suspected Nepalese patients of different hospitals. Rapid immunochromatographic
      test kit was used for early diagnosis and enzyme immunosorbent was chosen as a
      reference assay. RESULTS: The sensitivity and specificity of rapid test was 70%
      and 76.54% respectively whereas the prevalence of the disease was 38.17%. The
      odds ratio for males was 1.8 however; the association with the disease was
      statistically not significant. CONCLUSION: The diagnostic accuracy of rapid
      immunochromatographic test for dengue diagnosis was low (k=0.46). So, it should
      be substituted by highly sensitive test device for prompt diagnosis and health
      personnel should consider appropriate timing of sample collection for better
      performance of rapid test.

PMID- 22971854
TI  - Clinical evaluation of intrabony defects in localized aggressive periodontitis
      patients with and without bioglass- an in-vivo study.
AB  - BACKGROUND: Aggressive periodontitis is a specific type of periodontitis with
      clearly identifiable clinical characteristics such as rapid attachment loss, bone
      destruction and familial aggregation. Regeneration of mineralized tissues
      affected by aggressive periodontitis comprises a major scientific and clinical
      challenge. In recent years some evidence has been provided that bioactive glass
      is also capable of supporting the regenerative healing of periodontal lesions.
      OBJECTIVE: The aim of this clinical and radiological prospective study was to
      evaluate the efficacy of bioactive glass in the treatment of intra-bony defects
      in patients with localized aggressive periodontitis. METHODS: Twelve localized
      aggressive periodontitis patients with bilaterally located three-walled intra
      bony defect depth = 2 mm, preoperative probing depths = 5 mm were randomly
      treated either with the bioactive glass or without the bioactive glass. The
      clinical parameters plaque index, gingival index, probing depth, gingival
      recession, clinical attachment level, and mobility were recorded prior to surgery
      as well as 12 months after surgery. Intraoral radiographs were digitized to
      evaluate the bone defect depth at baseline and 12 months after the surgery.
      RESULTS: After 12 months, a reduction in probing depth of 3.92 + 0.313 mm (P <
      0.001) and a gain in clinical attachment level of 4.42+0358mm (P < 0.001) were
      registered in the test group. In the control group, a reduction in probing depth
      of 2.5 +0.230mm (P <0.001) and a gain in clinical attachment level of 2.58 +
      0.149 mm (P <0.001) was recorded. Radiographically, the defects were found to be
      filled by 2.587 + 0.218 mm (P < 0.001) in the test group and by 0.1792 + 0.031mm
      (P < 0.001) in the control group. Changes in gingival recession showed no
      significant differences. . CONCLUSION: Highly significant improvements in the
      parameters Probing depth, Clinical attachment level, and Bone defect depth were
      recorded after 12 months, with regenerative material.

PMID- 22971855
TI  - Estimation of stature from foot length in adult Nepalese population and its
      clinical relevance.
AB  - BACKGROUND: Stature is the height of the person in the upright posture. It is an
      important measure of physical identity. Interrelationships among different body
      measurements may be used to estimate one from another in case of missing body
      parts. OBJECTIVE: Stature is an important indicator for identification. There are
      numerous means to establish stature and their significance lies in the simplicity
      of measurement, applicability and accuracy in prediction. The current study dealt
      with developing a regression equation for stature estimation from foot length and
      to find out the correlation between body height and foot length of Nepalese
      people. METHODS: The present study was carried out to establish the regression
      equation and correlation coefficient between individual height and mean foot
      length. It was conducted on 440 students of age group 17 to 25 years studying in
      Kathmandu University School of Medical Sciences, Dhulikhel, Nepal. Body height
      and foot length were measured in centimeter. RESULTS: There was significant
      correlation between height and foot length (r = 0. 703, p < 0.01).The regression
      equation for height and foot length was found to be Y = 3.179 X + 87.65, where X
      is the foot length and Y the height. CONCLUSIONS: This study will help in medico
      legal cases in establishing identity of an individual and this would be useful
      for Anatomists and Anthropologists to calculate stature of adult Nepalese based
      on foot length.

PMID- 22971856
TI  - Is ethnicity an important determinant of high blood pressure in Nepalese
      population? A community-based cross sectional study in Duwakot, Nepal.
AB  - Background Hypertension is a rising public health problem in Nepal. Most of the
      upsurge is attributed to the behavioural and lifestyle transitions. However, the
      hereditary component such as ethnicity, which may also be an important
      determinant, has not been studied. Objective This study aims to investigate if
      ethnicity is a key determinant of having a high blood pressure in the Nepalese
      population. Methods A population-based cross sectional study was conducted in the
      Duwakot village of Bhaktapur District, Nepal. Systematic random sampling of the
      adults was done in all the nine wards. A total of 641 adults of both sexes, of
      age 35 years or more were included in the analysis. Results Most of the life
      style related risk factors were comparable in the broad two ethnic groups- Tibeto
      Burmans and Indo-Aryans. The prevalence of hypertension was 25.3% in the Tibeto
      Burmans compared to the 14.0% in the Indo-Aryans. Crude odds ratio (95% CI) of
      being hypertensive for the Tibeto-Burmans compared to the Indo-Aryans was 2.07
      (1.36-3.15) (p=0.01). After adjusting for the different factors the adjusted odds
      ratio (95% CI) for the same was found to be 1.78 (1.12-2.81) (p=0.014).
      Conclusion There is an ethnic variation in the blood pressure distribution in the
      Nepalese population, which might be acting independent of the different life
      style factors. More elaborate studies, including longitudinal and migration
      studies, and probably genetic analyses, can provide a more definite answer.

PMID- 22971857
TI  - Current fluoroquinolone susceptibility criteria for Salmonella needs re
      evaluation.
AB  - BACKGROUND: Disc diffusion technique is the routine susceptibility testing
      procedure for isolates of enteric fever, the most common clinical diagnosis among
      febrile patients in Nepal. OBJECTIVE: To evaluated the current fluoroquinolones
      (FQs) susceptibility criteria and nalidixic acid screening test in Salmonella
      enterica serovar Typhi and Paratyphi A. METHODS: S. Typhi and Paratyphi A strains
      isolated from 443 suspected enteric fever patients visiting National Public
      Health Laboratory (NPHL) during April through October 2008 were analyzed. All
      isolates were confirmed by standard microbiological procedures including
      serotyping. Antibiotic susceptibility testing was performed by using Kirby Bauer
      disc diffusion method and Clinical and Laboratory Standards Institute (CLSI)
      approved interpretive criteria. Agar dilution method was used to determine
      Minimum Inhibitory Concentration (MIC) of ciprofloxacin, ofloxacin and nalidixic
      acid. RESULT: Out of 41 Salmonella isolates, 80.49% were nalidixic acid
      resistant, with S. Paratyphi A showing higher resistance rate (88.23%) compared
      to S. Typhi (75%). The difference in both MIC and zone diameter in nalidixic acid
      susceptible and nalidixic acid resistant isolates was found to be significant (P
      < 0.001) and decreased susceptibility to FQs was strongly correlated (sensitivity
      and specificity of 100%) with resistance to nalidixic acid. Regression analysis
      of MIC against zone diameter based on the current CLSI recommended guidelines
      suggests that accommodation of current susceptible and resistant MIC requires
      increase in the zone diameter of ciprofloxacin and ofloxacin. CONCLUSION: Before
      using these drugs for management of enteric fever, appropriate identification of
      Salmonella isolates with reduced susceptibility to FQs is essential to limit the
      possible treatment failure and development of highly resistant strains. The
      current FQs susceptibility break point criteria for Salmonella need re
      evaluation.

PMID- 22971858
TI  - "Epizoonosis of dermatophytosis": a clinico- mycological study of dermatophytic
      infections in central Nepal.
AB  - BACKGROUND: Identification of dermatophytic species in clinical settings are
      important not only for epidemiological but also for the treatment. OBJECTIVES:
      Present study was carried out to find out the clinical variants of
      Dermatophytosis and species of fungus responsible for the disease. METHODS: The
      prospective observational analysis of 200 clinically suspected cases of
      dermatophytic infection attending Dermatology department of College of Medical
      Sciences Teaching Hospital, Bharatpur, Chitwan, Nepal. Skin scraping, hair and
      nail samples were collected and processed according to standard protocol.
      RESULTS: Maximum number of patients enrolled in study were reported for treatment
      5-8 weeks after the onset of disease. Overall male predominance was observed and
      ages between 26-30 years. Tinea corporis was the most common clinical type of
      tinea with female dominance in our study. 10 % of cases were having extensive
      Tinea. 71.5% of samples were positive on direct microscopy and 62 % positive on
      culture. Samples from T capitis were highest positive by direct microscopy (80%)
      and over all dominant species of fungus isolated in our study was Trichophyton
      verrucosum (30.6%). CONCLUSIONS: The study highlighted Tinea corporis as the most
      common clinical type with female predominance. Overall predominant causative
      fungal species isolated was Trichophyton verrucosum.

PMID- 22971859
TI  - The utilization of health care services and their determinants among the elderly
      population of Dhulikhel municipality.
AB  - BACKGROUND: Population ageing is a common problem faced in many countries world
      wide. Due to physiological and biochemical changes in the elderly, increased
      incidence of diseases is observed. There is often low use of health services by
      the elderly for a variety of reasons. OBJECTIVE: To examine the status of health
      care utilization and to determine the factors associated with utilization of
      health care among the elderly population of Dhulikhel Municipality. METHODS: A
      quantitative descriptive-cross sectional study, with a total number of 200
      elderly people residing in Dhulikhel Municipality, was selected for the study.
      Data were collected across the months of June - July 2011 applying two-staged
      cluster and systematic random sampling method. Both descriptive and inferential
      statistics were measured. RESULTS: Sixty eight percent of the elderly visited
      medical personnel in the past year. Eight percent of them visited the emergency
      department where most of them reported with symptoms attributed to heart disease.
      Among 200 elderly, 12.5% of them were admitted to the hospital and 53.0% utilized
      diagnostic services. Age, marital status, activities of daily living, and regular
      medication showed significant association with health services utilization at 95%
      level of confidence (p >0.05). CONCLUSION: Marital status, daily living habits,
      existence of chronic disease, and regular medication demonstrated significant
      association with the utilization of health care. Social support services,
      informal education, and awareness programs targeting the senior citizens and
      studies covering a diverse population are recommended.

PMID- 22971860
TI  - Oxygen saturation of hemoglobin in healthy children of 2-14 years at high
      altitude in Nepal.
AB  - BACKGROUND: Individuals residing at higher altitude may have oxygen saturation of
      hemoglobin different to those living at lower altitude. OBJECTIVES: To find out
      the baseline value of SpO2 in healthy Nepali children (2-14 years) living
      permanently at high altitude using pulse oximeter and also to study the relation
      of SpO2 with age, sex and ethnicity. METHODS: A descriptive observational study
      was conducted at 4 different altitudes ranging from 2700 to 3800 m in Mustang
      district. The mean pulse oximery values at different altitudes were calculated
      and compared. RESULTS: One hundred six children were enrolled with the median age
      of 10 years. The mean SpO2 value of children permanently residing at altitude
      2700m was 95.18%, at 2800m was 94.82%, at 3550m was 94.1% and 3800m was 93.1%.The
      difference in the SpO2 values at different altitude was statistically
      significant. No sex or age wise differences were noted on the mean SpO2 values in
      the study group. CONCLUSIONS: The mean SpO2 values were higher than several other
      studies done in the altitude above 2500 meters. Enrollment of older children and
      the different ethnic background could be the contributing factors for the
      differences.

PMID- 22971861
TI  - The role of argyrophilic nucleolar organizer region (AgNoR) study in cytological
      evalution of fluids, especially for detection of malignancy.
AB  - BACKGROUND: Serous effusion smears reported as (suspicious for malignancy) pose
      problems in clinical management. Silver staining for argyrophilic nucleolar
      organizer regions (AgNOR) has proved useful in making a cytopathologic
      differential diagnosis between benign and malignant cells. Nucleolar organizer
      regions(NORs) are loops of DNA located in acrocentric chromosomes. These NORs are
      visualized by silver staining technique that recognizes these argyrophilia
      associated proteins which are increased in malignancy. OBJECTIVE: This study
      aimed to distinguish reactive mesothelial cells from malignant cells in serous
      effusions using these NORs. METHODS: A total of 174 serous effusions received at
      the Department of Pathology, TUTH, during a period of one year were included in
      the study. Smears were studied by conventional Papanicolaou and Giemsa stains.
      AgNOR counts, variation in size and dispersion of AgNOR dots in smears were
      graded and compared in malignant and non-malignant effusions. RESULTS: Mean AgNOR
      counts of 10.43+?-0.73 and 10.21+?-0.51 in malignant peritoneal and pleural
      effusions, respectively, were significantly (p < 0.0001) greater as compared with
      counts of 2.12 +?- 0.54 and 2.11 +?- 0.54 in non-malignant effusions. The AgNORs
      were irregular in shape in malignant effusions whereas they were comparatively
      larger, single dots in benign effusions. AgNOR size and dispersion were of higher
      grade in significantly greater proportion of malignant as compared with non
      malignant effusions (p < 0.0001). Of the cytologically suspicious samples, nine
      were in the malignant range and one was in the benign range. CONCLUSION: AgNOR
      study appears to be clinically useful as an additional diagnostic tool for use in
      serous effusion when the cytologic diagnosis is difficult.

PMID- 22971862
TI  - Stigma related to tuberculosis among patients attending DOTS clinics of Dharan
      municipality.
AB  - BACKGROUND: The patients suffering from tuberculosis are receiving shame and
      unfair treatment from the people living around them within their own society
      attending DOTS clinic of Dharan municipality. OBJECTIVE: To assess the stigma
      experienced by tuberculosis patients and to find out the association between
      stigma experienced by Tuberculosis patient and the selected variables (socio
      demographic characteristics, clinical profile and illness experience). METHODS:
      Descriptive Cross Sectional study was done among sixty tuberculosis patients.
      Stratified random sampling was used to select the main center and sub center of
      Tuberculosis treatment and population proportionate simple random sampling using
      lottery method was done. Data was collected using predesigned, pretested performa
      from Explanatory Model Interview Catalogue developed by World Health
      Organization. RESULTS: The study revealed that 63.3% of the subjects were
      stigmatized. There was association between stigma and variables such as
      occupation, monthly family income and past history of Tuberculosis. There was
      also association of stigma with treatment phase, category of the patient and past
      outcome of illness. CONCLUSION: Due to lack of knowledge and awareness about
      Tuberculosis, many patients were stigmatized. Efforts should be made to educate
      the public about Tuberculosis to reduce stigma experienced by Tuberculosis
      patients and improve the compliance of the patient.

PMID- 22971863
TI  - Adenomyosis at hysterectomy: prevalence, patient characteristics, clinical
      profile and histopatholgical findings.
AB  - BACKGROUND: Underlying adenomyosis is often the cause of treatment failure for
      patients undergoing medical therapy for abnormal uterine bleeding and or chronic
      pelvic pain. Given the limitation of ultrasonography in diagnosing adenomyosis
      and MRI being unaffordable to most of the patients belonging to developing
      countries like us, it often remains undiagnosed before a hysterectomy. OBJECTIVE:
      To find out the clinical profile associated with adenomyosis and to determine the
      prevalence of adenomyosis in hysterectomy specimens; frequency distribution, as
      well as to correlate clinical examination with histopathological examination.
      METHODS: A total of 60 women who had undergone hysterectomy with
      histopathologically proven adenomyosis between April 2009 and March 2010 were
      included . Data were collected on indication for the intervention, age, symptoms,
      clinical findings, hemoglobin, menopausal status, gross and histopathological
      findings. RESULTS: A total of 256 women were scheduled for hysterectomy.
      Adenomyosis was diagnosed in 60 of 256 cases (23.4%). Menorrhagia (91.2%),
      dysmenorrhoea (84.2%), lower abdominal pain (84.2%) beginning later in
      reproductive life (mean age- 45yrs) is the classic presentation. Adenomyosis was
      present in 10 of 61 patients (16.3%) with fibroids; 27 of 60 (45%) with abnormal
      uterine bleeding; 11 of 55 (20%) with prolapse; four of 35 (11.4%) with ovarian
      mass; five of 25 (20%) with chronic pelvic pain; three of four (75%) with
      endometriosis. CONCLUSION: Women undergoing hysterectomy with diagnosis of
      adenomyosis have a distinct symptomatology. The choice of therapy in adenomyosis
      is hysterectomy for those women who have completed family and had failed medical
      therapy .

PMID- 22971864
TI  - Comparative study of effectiveness of oral acyclovir with oral erythromycin in
      the treatment of Pityriasis rosea.
AB  - BACKGROUND: Pityriasis rosea is an acute, self-limiting disease, probably
      infective in origin, affecting mainly children and young adults, characterized by
      distinctive skin eruptions and minimal constitutional symptoms. Both oral
      Erythromycin and oral Acyclovir have been used in its management. OBJECTIVES: To
      compare the effectiveness of oral Erythromycin and oral Acyclovir in the
      treatment of Pityriasis rosea. METHOD: Forty two patients with clinical diagnosis
      of Pityriasis rosea were enrolled. They were randomized into two groups. One
      group was given high-dose oral Acyclovir and another group oral Erythromycin in
      standard dose. The participants were evaluated one, two, four, six and eight
      weeks and six months after commencement of the study. RESULTS: Forty two patients
      including 26 males and 16 females completed the study. After 8th week, all
      patients showed complete response in both the groups. The response to oral
      Acyclovir compared with that to oral Erythromycin was better and was
      statistically significant in 1st, 2nd, 4th and 6th weeks. CONCLUSION: Although it
      is a self-limiting disease which resolves within three weeks to three months,
      this study reveals that both oral Acyclovir and oral Erythromycin are helpful in
      decreasing the severity and duration of Pityriasis rosea. Moreover, the study
      also indicates that oral Acyclovir is more effective than oral Erythromycin in
      reducing the severity and duration of Pityriasis rosea.

PMID- 22971865
TI  - Comparative analysis between objective structured clinical examination (OSCE) and
      conventional examination (CE) as a formative evaluation tool in Pediatrics in
      semester examination for final MBBS students.
AB  - BACKGROUND: The use of objective structured clinical examination in pediatrics is
      not common in undergraduate evaluation process. OBJECTIVE: To evaluate the
      effectiveness of objective structured clinical examination as compare to
      conventional examination as formative assessment tool in Pediatrics. METHODS: We
      conducted a cross sectional comparative study in defined population of 9th
      semester MBBS students to evaluate the effectiveness of objective structured
      clinical examination as comparison to conventional examination as formative
      assessment tool in Pediatrics. We analyzed the perception of objective structured
      clinical examination among the students. RESULTS: Fifty-two students appeared for
      the objective structured clinical examination evaluation on the first day and 42
      turned up for conventional examination on the next day. The 42 students who
      turned up for both examinations were asked to respond to the perception
      evaluation questionnaire. Comparison of the two examination styles showed that
      students fared better in objective structured clinical examination than in
      conventional examination both with respect to mean total score (p less than
      0.001) as well as mean percentage score. Out of the 42 subjects who appeared in
      both examinations, all passed in objective structured clinical examination and 35
      passed in conventional examination, this difference was significant by McNemar
      chi-square test (p = 0.016). 73.8% of the students opined in favor of objective
      structured clinical examination as a better formative assessment tool whereas
      9.5% students preferred conventional examination. CONCLUSIONS: Objective
      structured clinical examination a statistically significant better evaluation
      tool with comparison to conventional examination.

PMID- 22971866
TI  - Examination of relationship of scores obtained in grades 10 and 12 with the entry
      and success in undergraduate medical education.
AB  - BACKGROUND: Entrance examination (admission test) is the most important and
      widely accepted method of student selection for admission into medical schools in
      Nepal. For many schools it is the only criterion of student selection.
      OBJECTIVES: To examine relationships of scores obtained in schooling (grade 10
      and 12), medical entrance and MBBS professional examinations in a cohort to
      identify predictive strength for entry into medical school and success in medical
      education. METHODS: Exam scores from grade 10 to medical entrance and
      professional exams of undergraduate medical education of a total of 118 medical
      students who entered medical school between 1994 and 1998 only through the merit
      of open competitive medical entrance examination at the BP Koirala Institute of
      Health Sciences (BPKIHS) were assessed. RESULTS: Student selection for admission
      in MBBS course at BPKIHS and their subsequent success were not determined by
      difference in outcomes of public and private management of schools at grade 10
      (selection p= 0.80 and success p= 0.32 ) and grade 12 (selection p= 0.59 and
      success p= 0.55). Grade 12 averaged scores had no relationship in getting these
      students selected for admission into medical course (r= 0.08, p= 0.37), but did
      show correlation with the overall success in medical education (r= 0.32, p=
      0.00). Scores in physics at grade 12 retained predictive strength in success in
      medical education (r= 0.19, p= 0.04). CONCLUSION: The present student selection
      criteria for medical education are not appropriate and need to incorporate other
      attributes of candidates along with cognitive aspects.

PMID- 22971867
TI  - Progeria: pathogenesis and oral manifestation--a review.
AB  - Our life span is genetically programmed and it is possible that a defect in
      produced proteins encoded by the longevity gene is a cause of aging. Progeria
      which is a rare, fatal genetic condition which affects between one in four
      million and one in eight million children of both sexes equally and characterized
      by premature and accelerated aging. The appearance and physiology of these
      children resembles to elderly people but they typically have life span to their
      mid teens. It is also known as the Hutchinson-Gilford syndrome, which was
      initially reported by Johnathan Hutchinson in 1886 and further described by
      Hastings Gilford in 1904. It is an autosomal recessive disorder, which means an
      individual has inherited a mutated gene from both parents. It is added to the
      expanding catalogue of laminopathies, diseases caused by mutations affecting
      nuclear lamina proteins known as lamin A (LMNA). In oral manifestation primary
      finding is micrognathia with delayed tooth eruption and incomplete formation of
      root of permanent tooth. Presently there are no known cures for this abnormality.

PMID- 22971869
TI  - Concurrent vitiligo and psoriasis.
AB  - Coexistence of vitiligo and psoriasis in a single patient is a rare occurrence.
      The exact pathogenesis of this coexistence is obscure. Various autoimmune
      disorders are reported to occur more frequently in patients with both diseases. A
      case of this interesting coexistence seen on a 26 year old female patient who
      presented to the dermatology department of Dhulikhel hospital is presented here.
      She also had hypothyroidism. The possible pathogenesis and literature review of
      this rare condition is discussed here.

PMID- 22971868
TI  - Preventing dental caries in children: Indian scenario.
AB  - The prevalence of dental caries in developing countries like India is increasing
      to an alarming level in contrast to developed countries where it has decreased
      because of variety of preventive measures at the community and individual level.
      There is no State or Centre funded programs for prevention of dental diseases in
      India. The present review enlists the targeted prevention of dental caries in
      permanent teeth of 6 to 16 years old children presenting for dental care.

PMID- 22971870
TI  - Severe immune thrombocytopenic purpura treated with plasma exchange.
AB  - Immune thrombocytopenic purpura (ITP) is a hematological disorder characterized
      by immunologically mediated destruction of platelets and absence of other causes
      of thrombocytopenia. Treatment is required when the low platelet count entails
      risk of serious bleeding. Steroid is the first line of management. Acute
      refractory ITP with very low platelet count is variably treated with high dose
      steroid, intravenous immunoglobulin (IVIg), anti D or emergency splenectomy.
      Here, we present a case of steroid resistant ITP with severe thrombocytopenia
      treated with plasma exchange and low dose IVIg who responded dramatically to the
      therapy with maintained platelet count till one month from the institution of
      therapy.

PMID- 22971871
TI  - Bilateral high-orgin anterior tibial arteries and its clinical importance.
AB  - Reported here is a case of bilateral high - origin anterior tibial arteries as
      detected during routine dissection of a 40 years old male cadaver at the
      Kathmandu University School of Medical Sciences, Kavre District, Nepal. The aim
      of the present study was to underline the clinical importance of high origin of
      anterior tibial artery from the popliteal artery.The high origin anterior tibial
      artery from the popliteal artery and its relations with the popliteus muscle is
      an important anatomical variation which should be paid attention during knee
      joint surgery, total knee arthroplasty and angiographic evaluations.

PMID- 22971873
TI  - Medicine and smart phones.

PMID- 22971872
TI  - Association of seizure, facial dysmorphism, congenital umbilical hernia and
      undescended testes.
AB  - With the advances in neurogenetics association of epilepsy and intellectual
      disability with chromosomal abnormalities are being increasingly recognized.
      While onset of seizures with mental retardation at an early age indicate
      chromosomal abnormality, combination of characteristics facial dysmorphism and
      congenital abnormalities gives a clue of a particular syndrome. In addition MRI
      findings may help in confirming the diagnosis. A nine years old boy is presented
      where early onset seizure, mental retardation, delayed development of speech,
      presence of facial dysmorphism,, umbilical hernia and undescended testes
      suggested possibility of chromosomal 6q deletion disorder. Important deletion
      disorders are discussed and importance of clinical examination is stressed.

PMID- 22971874
TI  - Unusual pyrrolyl 4-quinolinone alkaloids from the marine-derived fungus
      Penicillium sp. ghq208.
AB  - One new pyrrolyl 4-quinolinone alkaloid, penicinoline E (1), together with three
      known deriverites, methyl-penicinoline (2), penicinoline (3), and quinolactacide
      (4), were isolated from the marine-derived fungus Penicillium sp. ghq208. The
      structures of these isolated compounds were elucidated by spectroscopic methods.
      Compounds (2, 3) exhibited moderate cytotoxicities against the HepG2 cell line
      with IC(50) values of 11.3 and 13.2 uM, respectively.

PMID- 22971875
TI  - Adjusted confidence intervals for a bounded parameter.
AB  - It is well known that the regular likelihood ratio test of a bounded parameter is
      not valid if the boundary value is being tested. This is the case for testing the
      null value of a scalar variance component. Although an adjusted test of variance
      component has been suggested to account for the effect of its lower bound of
      zero, no adjustment of its interval estimate has ever been proposed. If left
      unadjusted, the confidence interval of the variance may still contain zero when
      the adjusted test rejects the null hypothesis of a zero variance, leading to
      conflicting conclusions. In this research, we propose two ways to adjust the
      confidence interval of a parameter subject to a lower bound, one based on the
      Wald test and the other on the likelihood ratio test. Both are compatible to the
      adjusted test and parametrization-invariant. A simulation study and two examples
      are given in the framework of ACDE models in twin studies.

PMID- 22971876
TI  - Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes.
AB  - Magnetic resonance imaging (MRI) yields high spatially resolved contrast with
      anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning.
      To improve imaging sensitivity, adding contrast agents accelerates the relaxation
      rate of water molecules, thereby greatly increasing the contrast between specific
      issues or organs of interest. Currently, the majority of T(1) contrast agents are
      paramagnetic molecular complexes, typically Gd(iii) chelates. Various
      nanoparticulate T(1) and T(1)/T(2) contrast agents have recently been
      investigated as novel agents possessing the advantages of both the T(1) contrast
      effect and nanostructural characteristics. In this minireview, we describe the
      recent progress of these inorganic nanoparticle-based MRI contrast agents.
      Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and
      ultrasmall iron oxide/ferrite nanoparticles.

PMID- 22971877
TI  - Influence of structural properties on ballistic transport in nanoscale epitaxial
      graphene cross junctions.
AB  - In this paper we investigate the influence of material and device properties on
      the ballistic transport in epitaxial monolayer graphene and epitaxial quasi-free
      standing monolayer graphene. Our studies comprise (a) magneto-transport in two
      dimensional (2D) Hall bars, (b) temperature- and magnetic-field-dependent bend
      resistance of unaligned and step-edge-aligned orthogonal cross junctions, and (c)
      the influence of the lead width of the cross junctions on ballistic transport. We
      found that ballistic transport is highly sensitive to scattering at the step
      edges of the silicon carbide substrate. A suppression of the ballistic transport
      is observed if the lead width of the cross junction is reduced from 50 nm to 30
      nm. In a 50 nm wide device prepared on quasi-free-standing graphene we observe a
      gradual transition from the ballistic into the diffusive transport regime if the
      temperature is increased from 4.2 to about 50 K, although 2D Hall bars show a
      temperature-independent mobility. Thus, in 1D devices additional temperature
      dependent scattering mechanisms play a pivotal role.

PMID- 22971878
TI  - High neighborhood walkability mitigates declines in middle-to-older aged adults'
      walking for transport.
AB  - BACKGROUND: Neighborhood walkability shows significant positive relationship with
      residents' walking for transport in cross-sectional studies. We examined
      prospective relationships of neighborhood walkability with the change in walking
      behaviors over 4 years among middle-to-older aged adults (50-65 years) residing
      in Adelaide, Australia. METHODS: A baseline survey was conducted during 2003
      2004, and a follow-up survey during 2007-2008. Walking for transport and walking
      for recreation were assessed at both times among 504 adults aged 50-65 years
      living in objectively determined high- and low-walkable neighborhoods. Multilevel
      linear regression analyses examined the associations of neighborhood walkability
      with changes over 4 years in walking for transport and walking for recreation.
      RESULTS: On average, participants decreased their time spent in walking for
      transport (-4.1 min/day) and for recreation (-3.7 min/day) between the baseline
      and 4-year follow-up. However, those living in high-walkable neighborhoods showed
      significantly smaller reduction (adjusted mean change: -1.1 min/day) in their
      time spent in walking for transport than did those living in low-walkable
      neighborhoods (-6.7 min/day). No such statistically-significant differences were
      found with the changes in walking for recreation. CONCLUSIONS: High-walkable
      neighborhoods may help middle-to-older aged adults to maintain their walking for
      transport.

PMID- 22971879
TI  - Difference in caloric expenditure in sitting versus standing desks.
AB  - BACKGROUND: Traditional desks require students to sit; however, recently schools
      have provided students with nontraditional standing desks. The purpose of this
      study was to investigate differences in caloric expenditure of young adults while
      sitting at a standard classroom desk and standing at a nontraditional standing
      classroom desk. METHODS: Twenty (10 male/10 female) young (22.8 +/- 1.9 y),
      healthy participants reported to the laboratory between the hours of 7:00 AM and
      2:00 PM following a 12-h fast and 48-h break in exercise. Participants were
      randomly assigned to perform a series of mathematical problems either sitting at
      a normal classroom desk or standing at a nontraditional standing desk. Inspired
      and expired gases were collected for 45-min for the determination of oxygen
      consumption (VO2), carbon dioxide production (VCO2), and minute ventilation (VE)
      using a metabolic gas system. RESULTS: There were significant increases from
      sitting to standing in VO2 (0.22 +/- 0.05 vs. 0.28 +/- 0.05 L.min-1, P <= .0001),
      VCO2 (0.18 +/- 0.05 vs. 0.24 +/- 0.050 L.min-1, P <= .0001), VE (7.72 +/- 0.67
      vs. 9.41 +/- 1.20 L.min-1, P <= .0001), and kilocalories expended per minute
      (1.36 +/- 0.20 kcal/min, P <= .0001 vs. 1.02 +/- 0.22 kcal/min, P <= .0001).
      CONCLUSIONS: Results indicate a significant increase in caloric expenditure in
      subjects that were standing at a standing classroom desk compared with sitting at
      a standard classroom desk.

PMID- 22971880
TI  - Relationships between negative affect and academic achievement among secondary
      school students: the mediating effects of habituated exercise.
AB  - BACKGROUND: The current study was undertaken to examine the associations between
      self-determination, exercise habit, anxiety, depression, stress, and academic
      achievement among adolescents aged 13 and 14 years in eastern Malaysia. METHODS:
      The sample consisted of 750 secondary school students (mean age = 13.4 years, SD
      = 0.49). Participants completed self-report measures of exercise behavioral
      regulation, negative affect, and exercise habit strength. Midyear exam results
      were used as an indicator of academic performance. Structural equation modeling
      was used to analyze the data. RESULTS: The results of structural equation
      modeling revealed a close model fit for the hypothesized model, which indicates
      that higher levels of self-determination were positively associated with
      habituated exercise behavior. In turn, exercise habit strength fostered academic
      achievement and buffered the debilitative effect of stress, depression, and
      anxiety on student academic performance. The analysis of model invariance
      revealed a nonsignificant difference between male and female subjects.
      CONCLUSION: The findings support the notion that habituated exercise fosters
      academic performance. In addition, we found that habituated exercise buffers the
      combined effects of stress, anxiety and depression on academic performance. The
      finding also supports the roles of self-determination in promoting exercise
      habituation.

PMID- 22971881
TI  - Modeling the impact of prepregnancy BMI, physical activity, and energy intake on
      gestational weight gain, infant birth weight, and postpartum weight retention.
AB  - BACKGROUND: A "fit pregnancy" requires balancing energy expenditure with energy
      intake (EI) to achieve appropriate gestational weight gains (GWG), healthy infant
      birth weights (IBW), and minimal postpartum weight retention (PPWR). Our
      objective was to develop an integrated conceptual framework to assess the
      contribution of prepregnancy weight (PP-BMI), EI, and physical activity (PA) as
      determinants of GWG, IBW, and PPWR. METHODS: Pregnant women (n = 59) were
      recruited from prenatal classes. Energy intake was estimated using 3 24-hr diet
      recalls and PA using a validated PA questionnaire and a pedometer. Telephone
      interviews at 6-weeks postpartum assessed self-reported GWG, IBW, and PPWR.
      Hierarchical multiple regression analyses were used to explore the potential
      predictors of GWG, IBW, and PPWR. RESULTS: Prepregnancy BMI was associated with
      GWG, and EI was associated with IBW; each model captured only 6%-18% of the
      variability. In contrast, PPWR was predicted by PP-BMI, GWG, and EI, which
      together explained 61% of its variability, whereas GWG alone explained 51% of the
      variability in PPWR. CONCLUSIONS: Modeling the relationship using hierarchical
      models suggests that PP-BMI, prepartum PA, and EI differentially impact GWG, IBW,
      and PPWR.

PMID- 22971882
TI  - Assessment of the benefit of powered exercises for muscular endurance and
      functional capacity in elderly participants.
AB  - BACKGROUND: Aging is accompanied by a significant loss of strength which further
      contributes to loss of functional ability and a propensity for injury. The
      purpose of this study was to assess the effectiveness of power assisted exercises
      on muscle endurance and functional capacity of elderly participants following 12
      weeks of supervised training. METHODS: Elderly subjects (N = 53) were randomly
      assigned to either the experimental or the control group. The experimental group
      trained for 12 weeks using powered exercise machines incorporating only
      concentric contractions while attempting to accelerate the preset, moving levers.
      Training involved 6 separate machines and using both upper- and lower-body
      musculature. Pre- and posttests consisted of Timed Chair Stand, Up and Go Test,
      arm curl, bench press, leg extension, triceps extension, and the Berg Balance
      Scale Assessment. RESULTS: Analysis yielded significant improvements (P < .05) by
      the experimental group over the control group in all measures of muscle
      endurance, balance, and functional capacity. An improvement in balance paralleled
      muscle endurance improvements. CONCLUSIONS: Powered exercise equipment when used
      actively, will generate both upper- and lower-body muscle endurance in elderly
      participants in a safe exercise environment and such improvement also generated
      improvement in balance.

PMID- 22971883
TI  - Physical activity in rheumatoid arthritis: a systematic review.
AB  - BACKGROUND: Physical activity is associated with improved health outcomes in many
      populations. It is assumed that physical activity levels in the rheumatoid
      arthritis (RA) population may be reduced as a result of symptoms of the disease.
      The objective of this review is to establish the current evidence base for levels
      of physical activity in the RA population. METHODS: A systematic review was
      performed of 7 databases (Emabase, MEDLINE, AMED, Biomedical Reference Collection
      Expanded, CINAHL, Nursing and Allied Health Collection, and SportsDiscus) up to
      February 2011 to examine the evidence in the area. RESULTS: One hundred and
      thirty-six studies were identified through electronic searching. One hundred and
      six were excluded based on title and/or abstract analysis and a further 14 were
      excluded based on full text analysis. Sixteen studies meeting the criteria were
      deemed suitable for inclusion. The results of the included studies indicate that
      the level of physical activity may be lower among individuals with RA when
      compared with healthy controls or normative data. CONCLUSIONS: There are a number
      of methodological considerations at play within the studies reviewed which
      prohibits definitive conclusion on the physical activity levels of this
      population group. Given the known health benefits of physical activity, further
      research in this area appears indicated.

PMID- 22971884
TI  - Validation and comparison of 3 accelerometers for measuring physical activity
      intensity during nonlocomotive activities and locomotive movements.
AB  - BACKGROUND: The current study evaluated the validity of 3 commercially-available
      accelerometers to assess metabolic equivalent values (METs) during 12 activities.
      METHODS: Thirty-three men and thirty-two women were enrolled in this study. The
      subjects performed 5 nonlocomotive activities and 7 locomotive movements. The
      Douglas bag method was used to gather expired air. The subjects also wore 3 hip
      accelerometers, a Lifecorder uniaxial accelerometer (LC), and 2 triaxial
      accelerometers (ActivTracer, AT; Actimarker, AM). RESULTS: For nonlocomotive
      activities, the LC largely underestimated METs for all activities (20.3%-55.6%)
      except for desk work. The AT overestimated METs for desk work (11.3%) and hanging
      clothes (11.7%), but underestimated for vacuuming (2.3%). The AM underestimated
      METs for all nonlocomotive activities (8.0%-19.4%) except for hanging clothes
      (overestimated by 16.7%). The AT and AM errors were significant, but much smaller
      than the LC errors (23.2% for desk work and -22.3 to -55.6% for the other
      activities). For locomotive movements, the 3 accelerometers significantly
      underestimated METs for all activities except for climbing down stairs.
      CONCLUSIONS: We conclude that there were significant differences for most
      activities in 3 accelerometers. However, the AT, which uses separate equations
      for nonlocomotive and locomotive activities, was more accurate for nonlocomotive
      activities than the LC.

PMID- 22971886
TI  - Prompts to increase stair climbing in stations: the effect of message complexity.
AB  - BACKGROUND/OBJECTIVE: While point-of-choice prompts consistently increase stair
      climbing, experimental comparisons of message content are rare. Here, the effects
      of 2 messages differing in complexity about the health outcomes obtainable from
      stair climbing were compared. METHODS: In a UK train station with 2 independent
      platforms exited by identical 39-step staircases and adjacent escalators,
      observers recorded travelers ascent method and gender from 8:00 A.M. to 10:00
      A.M. on 2 weekdays during February/March 2008 (n = 48,697). Baseline observations
      (2-weeks) preceded a 3-week poster phase. Two posters (594 * 841 mm) that
      differed in the complexity of the message were positioned at the point-of-choice
      between ascent methods, with 1 placed on each side of the station simultaneously.
      Logistic regression analysis was conducted in April 2010. RESULTS: Omnibus
      analysis contained main effects of the intervention (OR = 1.07, CI = 1.02-1.13, P
      = .01) and pedestrian traffic volume (OR = 5.42, CI = 3.05-9.62, P < .001).
      Similar effects occurred for complex (OR = 1.10, CI = 1.02-1.18, P = .01) and
      simple messages (OR = 1.07, CI = 1.01-1.13, P = .02) when analyses controlled for
      the influence of pedestrian traffic volume. There was reduced efficacy for the
      complex message during busier periods (OR = 0.36, CI = 0.20-0.66, P = .001),
      whereas the simple message was immune to these effects of traffic volume.
      CONCLUSIONS: Pedestrian traffic flow in stations can influence message
      effectiveness. Simple messages appear more suitable for busy sites.

PMID- 22971888
TI  - Assessing physical activity in Muslim women of South Asian origin.
AB  - BACKGROUND: We assessed the quality of data on physical activity obtained by
      recall from Muslim women of South Asian origin, and the feasibility of using
      accelerometer-based physical activity monitors to provide more objective measures
      of physical activity in this group. METHODS: In this largely qualitative study,
      22 British Pakistani women were asked to wear accelerometers (the GT1M Actigraph
      and/or the Sensewear Armband) for 4 days, provided 2 24-hour recalls of
      activities, and were interviewed about their experiences with the monitors.
      RESULTS: Women reported spending most of their time in housework and childcare,
      activities which generated the majority of recorded bouts of moderate to vigorous
      physical activity. However, women had difficulty in recalling the timing, and
      assessing the intensity, of these usually unstructured activities. A significant
      minority of accelerometer datasets were incomplete and some women reported either
      forgetting to wear the accelerometer or finding it intrusive. CONCLUSIONS:
      Questionnaires are unlikely to provide an accurate assessment of physical
      activity in this group of women. This suggests that accelerometer data will be
      preferable. However, collecting sufficient data for large-scale studies using
      activity monitors in this population will be challenging.

PMID- 22971892
TI  - A study on anti-mannose binding lectin (anti-MBL) antibodies and serum MBL levels
      in Indian systemic lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) is a prototype autoimmune disease
      characterized by systemic inflammation and autoantibody production. Anti-mannose
      binding lectin (anti-MBL) autoantibodies have been studied in SLE for their
      possible effect on mannose binding lectin (MBL) levels and functional activity.
      This study aimed at the detection of anti-MBL autoantibodies in Indian SLE
      patients and evaluates their relationship with related immunological parameters.
      Two hundred diagnosed SLE patients from Western India were included in the study
      where 87 patients were lupus nephritis (LN) (43.5 %) and remaining (56.5 %) were
      non-LN. Disease activity was assessed using the Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI). Anti-MBL autoantibodies to IgG and IgM isotypes,
      anti-C1q autoantibodies, MBL levels and circulating immune complex levels were
      detected by ELISA. C3, C4 and CRP levels were detected by nephelometer. Anti-MBL
      autoantibodies were detected in 52 % SLE patients, where 55 % had IgG-anti-MBL,
      33.8 % had IgM-anti-MBL and 11.3 % had both subclasses. Low MBL levels were
      present in 64.4 % anti-MBL positives as compared to 61.5 % in anti-MBL negatives.
      Among anti-MBL positives, 74 % had anti-C1q antibodies, whereas 41.7 % of anti
      MBL negatives had anti-C1q autoantibodies (p = 3.45E06). An inverse correlation
      was observed between serum MBL and CIC levels. A statistically significant
      difference was noted between anti-MBL positives and anti-MBL negative patients
      with hsCRP levels (p = 0.002). Occurrence of infections was higher among anti-MBL
      positives (65 %) as compared to anti-MBL negatives (35 %). The difference between
      SLEDAI scores among anti-MBL-positive and anti-MBL-negative groups was
      statistically insignificant. Anti-MBL autoantibodies in SLE patients can
      influence functional activity of MBL and have a significant role in SLE disease
      pathogenesis.

PMID- 22971893
TI  - Manganese alters rat brain amino acids levels.
AB  - Manganese (Mn) is an essential element and it acts as a cofactor for a number of
      enzymatic reactions, including those involved in amino acid, lipid, protein, and
      carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning,
      characterized by psychiatric disturbances and an extrapyramidal disorder. Mn
      induced neuronal degeneration is associated with alterations in amino acids
      metabolism. In the present study, we analyzed whole rat brain amino acid content
      subsequent to four or eight intraperitoneal injections, with 25 mg MnCl2/kg/day,
      at 48-h intervals. We noted a significant increase in glycine brain levels after
      four or eight Mn injections (p < 0.05 and p < 0.01, respectively) and arginine
      also after four or eight injections (p < 0.001). Significant increases were also
      noted in brain proline (p < 0.01), cysteine (p < 0.05), phenylalanine (p < 0.01),
      and tyrosine (p < 0.01) levels after eight Mn injections vs. the control group.
      These findings suggest that Mn-induced alterations in amino acid levels secondary
      to Mn affect the neurochemical milieu.

PMID- 22971894
TI  - Rosette-forming glioneuronal tumor -- evidence of stem cell origin with
      biphenotypic differentiation.
AB  - Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a new
      addition to the WHO classification of central nervous system tumors. To date, 72
      cases have been described in literature. In the present study, we report the
      clinical and imaging features, with detailed histopathological and
      immunohistochemical profile, of eight cases. Confocal microscopic evidence of
      stem cell origin with biphenotypic, glial and neurocytic differentiation is
      presented with a comprehensive review of literature.

PMID- 22971895
TI  - Adapting source grid parameters to improve the condition of the magnetostatic
      linear inverse problem of estimating nanoparticle distributions.
AB  - The problem of estimating magnetic nanoparticle distributions from
      magnetorelaxometric measurements is addressed here. The objective of this work
      was to identify source grid parameters that provide a good condition for the
      related linear inverse problem. The parameters investigated here were the number
      of sources, the extension of the source grid, and the source direction. A new
      measure of the condition, the ratio between the largest and mean singular value
      of the lead field matrix, is proposed. Our results indicated that the source
      grids should be larger than the sensor area. The sources and, consequently, the
      magnetic excitation field, should be directed toward the Z-direction. For
      underdetermined linear inverse problems, such as in our application, the number
      of sources affects the condition to a relatively small degree. Overdetermined
      magnetostatic linear inverse problems, however, benefit from a reduction in the
      number of sources, which considerably improves the condition. The adapted source
      grids proposed here were used to estimate the magnetostatic dipole from simulated
      data; the L2-norm, residual, and distances between the estimated and simulated
      sources were significantly reduced.

PMID- 22971896
TI  - Finite element modeling of mitral leaflet tissue using a layered shell
      approximation.
AB  - The current study presents a finite element model of mitral leaflet tissue, which
      incorporates the anisotropic material response and approximates the layered
      structure. First, continuum mechanics and the theory of layered composites are
      used to develop an analytical representation of membrane stress in the leaflet
      material. This is done with an existing anisotropic constitutive law from
      literature. Then, the concept is implemented in a finite element (FE) model by
      overlapping and merging two layers of transversely isotropic membrane elements in
      LS-DYNA, which homogenizes the response. The FE model is then used to simulate
      various biaxial extension tests and out-of-plane pressure loading. Both the
      analytical and FE model show good agreement with experimental biaxial extension
      data, and show good mutual agreement. This confirms that the layered composite
      approximation presented in the current study is able to capture the exponential
      stiffening seen in both the circumferential and radial directions of mitral
      leaflets.

PMID- 22971897
TI  - Inulin-rich fractions from Vernonia kotschyana roots have anti-ulcer activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Roots from Vernonia kotschyana are on the
      national list of essential drugs in Mali (West-Africa). It is sold under the name
      Gastrosedal and it used against ailments like gastritis and gastric ulcer. To
      evaluate the anti-ulcer, immunomodulating activities and toxicity of 50 and 100 
      degrees C water extracts, Vk50-I and Vk100-I respectively, from the roots of
      Vernonia kotschyana. MATERIALS AND METHODS: Characterization of extracts was
      carried out by GC, colorimetric and biological methods. Vk50-I and Vk100-I were
      administrated 50 min before induction of gastric ulcers in mice with 0.3 M HCl
      60% EtOH. Inhibition of ulcer formation was calculated based on lesion index.
      Immunological activities were measured by complement fixation and macrophage
      activation. Toxicity assay was carried out on brine shrimps. RESULTS: Vk50-I (98%
      inulin) and Vk100-I (83% inulin) from Vernonia kotschyana significantly inhibited
      the formation of gastric lesions in mice (100 mg/kg). No immunomodulating
      activities or toxicity were found. CONCLUSIONS: Our results show that inulin is
      probably partly responsible for the anti-ulcer activity of Gastrosedal. In
      addition, it is possible that water soluble polysaccharides (mainly inulin) have
      an indirect impact on the general health of the GI.

PMID- 22971898
TI  - Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK
      and NF-kappaB pathway in RAW 264.7 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum nitidium (Roxb.) DC. has long been
      used as a traditional herbal medicine for inflammatory diseases such as rheumatic
      arthritis and peridentitis. However, the anti-inflammatory mechanism of Nitidine
      chloride has not been fully elucidated. AIM OF THE STUDY: To determine the anti
      inflammatory effects and mechanism of Nitidine chloride (NTD), a pentacyclic
      alkaloid is isolated from the root of Z. nitidium, in murine macrophages.
      MATERIALS AND METHODS: Anti-inflammatory properties of NTD were investigated
      using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro
      model. The pro-inflammatory cytokines were evaluated by real-time RT-PCR and
      ELISA. Furthermore, intracellular signaling pathways were analyzed by Western
      blot and Immunofluorescence staining using specific antibodies. RESULTS: NTD
      significantly reduced the production of pro-inflammatory cytokines such as tumor
      necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in both
      RNA and protein level. Moreover, transcriptional activity of NF-kB as well as the
      phosphorylation of mitogen-activated protein kinases (MAPKs) in LPS-treated RAW
      264.7 was significantly inhibited by NTD in a dose dependent manner. These
      results suggested that NTD exerts an anti-inflammatory property by inhibiting TNF
      alpha, IL-1beta, and IL-6 production in association with reduced NF-kappaB and
      MAPK signaling pathways in RAW 264.7 cells. CONCLUSION: These results suggested
      that NTD exerts an anti-inflammatory property by inhibiting TNF-alpha, IL-1beta,
      and IL-6 production in association with reduced NF-kappaB and MAPK signaling
      pathways in RAW 264.7 cells. Nitidine chloride inhibits LPS-induced TNF alpha, IL
      1beta and IL-6 production via the suppression of phosphorylation of MAPK and the
      translocation of p65. In addition, these results revealed a novel role of NTD in
      regulation of inflammatory diseases.

PMID- 22971899
TI  - Topical application of an ethanol extract prepared from Illicium verum suppresses
      atopic dermatitis in NC/Nga mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Illicium verum is a traditional herbal medicine
      with anti-inflammatory properties used in Asia. However, its usefulness in the
      treatment of allergic diseases remains unclear. This study evaluated the anti
      inflammatory and antiallergic effects of I. verum extract (IVE) in a mouse model
      of atopic dermatitis. MATERIALS AND METHODS: We investigated the effects of IVE
      on compound 48/80-induced histamine release, and phorbol 12-myristate13-acetate
      and calcium ionophore A23187-stimulated cytokines secretion in MC/9 mast cells.
      Atopic dermatitis was induced in NC/Nga mice by exposure to extract of house dust
      mite (Dermatophagoides farinae). After a topical application of IVE on ear and
      skin lesions, we evaluated the severity of skin symptoms, ear thickness,
      inflammatory cell infiltration, and serum levels of immunoglobulin E (IgE),
      histamine, interleukin (IL)-6, and intercellular adhesion molecule (ICAM)-1. In
      addition, we determined the expression of IL-4, IL-6, tumor necrosis factor (TNF)
      alpha, interferon (IFN)-gamma thymus- and activation-regulated chemokine (TARC),
      regulated on activation, normal T cell expressed and secreted (RANTES), ICAM-1,
      and vascular cell adhesion molecule (VCAM)-1 in ear tissues. RESULTS: IVE
      inhibited secretion of histamine, IL-4, IL-6, and TNF-alpha from mast cells in a
      dose-dependent manner. Topical application of IVE significantly reduced
      dermatitis scores, ear thickness, and serum levels of IgE, histamine, IL-6, and
      ICAM-1. Histopathological analysis demonstrated decreased epidermal thickening
      and dermal infiltration by inflammatory cells. In the ear lesions, IVE treatment
      reduced expression of IL-4, IL-6, TNF-alpha, TARC, RANTES, ICAM-1, and VCAM-1,
      but not IFN-gamma. CONCLUSIONS: These results indicate that IVE inhibits atopic
      dermatitis-like skin lesions by suppressing the expression of cytokines,
      chemokines, and adhesion molecules. These results suggest that IVE may be a
      potential therapeutic candidate for atopic dermatitis.

PMID- 22971900
TI  - Side-effects of resveratrol in HepG2 cells: reduced pten and increased bcl-xl
      mRNA expression.
AB  - Resveratrol is a natural compound present in red grapes and red wine, and is
      often consumed in the human diet. The chemopreventive and chemotherapeutic
      potential of resveratrol in hepatocellular carcinoma (HCC), one of the most
      common types of liver cancer, has received much attention in recent years.
      However, the side-effects of resveratrol stimulation are of concern due to the
      high doses administered to humans. This study investigated the effects of
      resveratrol on the mRNA expression of pten and bcl-xl in HepG2 cells using semi
      quantitative and quantitative PCR. This study demonstrated that 200 umol/l
      resveratrol stimulation for 12 h resulted in the inhibition of HepG2
      proliferation, reduced pten and increased bcl-xl mRNA expression. The data
      suggest that (a) the anticancer mechanism of resveratrol does not involve the
      induction of pten and inhibition of bcl-xl expression and (b) resveratrol induces
      a cellular self-protection response, which underlies the cellular chemoresistance
      against resveratrol in HepG2 cells.

PMID- 22971902
TI  - Time to first cigarette and upper aerodigestive tract cancer risk in Japan.
AB  - BACKGROUND: Cigarette smoking is the major cause for upper aerodigestive tract
      (UADT) cancers. The time to first cigarette (TTFC) of the day is a distinct
      indicator of nicotine dependence, but scanty information is available on its
      possible relation with UADT cancers (oral, oropharyngeal, hypopharyngeal,
      laryngeal, nasopharyngeal, and esophageal cancers). METHODS: This case-control
      study includes a total of 1,009 incident UADT cancer cases and 3,027 age- and sex
      matched noncancer controls admitted to the Aichi Cancer Center (Nagoya, Japan)
      between 2001 and 2005. We estimated OR and 95% confidence intervals (CI) for TTFC
      using logistic regression models after adjustment for several potential
      confounders. RESULTS: TTFC was inversely related to the risk of UADT cancer, and
      this association was consistent across subtypes of head and neck cancer and
      esophageal cancer. For all UADT cancers considered among ever smokers and after
      accurate allowance for smoking quantity and duration, besides other relevant
      covariates, compared with TTFC more than 60 minutes, the adjusted ORs were 1.40
      (95% CI: 0.93-2.11) for 31 to 60 minutes, 1.76 (95% CI: 1.20-2.58) for 6 to 30
      minutes, and 2.43 (95% CI: 1.64-3.61) for within 5 minutes. No significant
      heterogeneity was found in strata of sex, age, alcohol consumption, fruit and
      vegetable intake, and occupation for overall and site-specific analysis.
      CONCLUSION: Nicotine dependence, as indicated by the TTFC, is associated with
      increased risk of UADT cancers and is therefore an independent marker of exposure
      to smoking. IMPACT: Our result indicates more detailed risk evaluation of UADT
      cancers that is enabled by the TTFC.

PMID- 22971901
TI  - Results of a randomized controlled trial testing the efficacy of a culturally
      targeted and a generic video on mammography screening among chinese-american
      immigrants.
AB  - BACKGROUND: Research comparing the effects of culturally targeted and generic but
      linguistically appropriate intervention programs is limited. We conducted a
      randomized controlled trial comparing the efficacy of a culturally targeted
      video, a generic video, and a fact sheet (control) in promoting mammography
      screening among Chinese-American immigrants. METHODS: We randomized 664 Chinese
      American women from the Washington, DC, and New York City areas who were older
      than 40 years and nonadherent to annual mammography screening guidelines to three
      study arms (each with ~221 women). The outcome was self-reported mammography
      screening 6 months post intervention. Measures of knowledge, Eastern cultural
      views, and health beliefs were administered before and after the intervention.
      RESULTS: The culturally targeted video, the generic video, and the fact sheet
      increased mammography use by 40.3%, 38.5%, and 31.1% from baseline, respectively.
      A significant intervention effect was observed only in one subgroup: The
      culturally targeted video significantly increased mammography screening among low
      acculturated women over the fact sheet [OR, 1.70; 95% confidence interval (CI),
      1.04-2.78]. Overall, women who obtained a mammogram during the follow-up period
      reported significantly fewer barriers to screening after intervention than those
      who had not obtained screening. Both of the video groups reported fewer barriers
      after intervention than the control group. CONCLUSIONS: Both theoretically guided
      videos increased the likelihood of mammography use to a similar extent. Cultural
      targeting was only effective for low-acculturated women. Both videos reduced
      perceived barriers to screening and consequently increased screening behavior.
      IMPACT: The results of this study provide empirical evidence on the efficacy of
      cultural targeting for minority immigrants.

PMID- 22971903
TI  - Searching for two things at once: establishment of multiple attentional control
      settings on a trial-by-trial basis.
AB  - Recent work has demonstrated that attention can be configured to multiple
      potential targets in spatial search. However, this previous work relied on a
      fixed set of targets across multiple trials, allowing observers to offload
      attentional control settings to longer-term representations. In the present
      experiments, we demonstrate multiple attentional control settings that operate
      independently of space (Experiments 1 and 2). More important, we show that
      observers can be cued to different control settings on a trial-by-trial basis
      (Experiment 3). The latter result suggests that observers were capable of
      maintaining multiple control settings when the demands of the task required an
      attentional search for specific feature values. Attention can be configured to
      extract multiple feature values in a goal-directed manner, and this configuration
      can be can be dynamically engaged on a trial-by-trial basis. These results
      support recent findings that reveal the high precision, complexity, and
      flexibility of attentional control settings.

PMID- 22971904
TI  - Suppression of cardiocirculatory responses to orthostatic stress by passive
      walking-like leg movement in healthy young men.
AB  - BACKGROUND: Although passive walking-like leg movement in the standing posture
      (PWM) has been used in the clinical field, the safety of PWM has not been fully
      determined despite the risks of orthostatic intolerance due to standing posture.
      The aim of the present study was to examine cardiocirculatory response during PWM
      in healthy young men. METHODS: The subjects (n = 13) spent 5 min in a sitting
      position and then 5 min in a quiet standing position to determine baseline
      levels. Thereafter, they underwent 25-min rhythmic PWM at 1 Hz while standing. In
      another bout, subjects experienced the same protocol except that they underwent
      25-min quiet standing (QS) instead of 25-min PWM. Two subjects dropped out of the
      25-min QS due to feeling of discomfort. Thus, data obtained in the remaining
      eleven subjects are presented. RESULTS: In the PWM trial, systolic arterial blood
      pressure (SAP) decreased from 112 +/- 8 mmHg during the sitting baseline period
      to 107 +/- 8 mmHg during the standing baseline period (p <0.05), while heart rate
      (HR) increased from 73 +/- 9 bpm during the sitting baseline period to 84 +/- 10
      bpm during the standing baseline period (p <0.001). After the imposition of PWM,
      SAP increased from 107 +/- 8 mmHg in the standing baseline period to 120 +/- 6
      mmHg (p <0.001), while HR decreased from 84 +/- 10 bpm in the standing baseline
      period to 76 +/- 9 bpm (p <0.05). In the QS trial, SAP, which had decreased
      during the standing baseline period compared to that during the sitting baseline
      period, remained lowered during the 25-min QS period, while HR, which had
      increased during the standing baseline period compared to that during the sitting
      baseline period, remained elevated during the 25-min QS period. In both bouts, HR
      showed almost mirror-image changes in the high-frequency component of HR
      variability, suggesting that the changes in HR were due to change in
      parasympathetic activation. Double product (HR * SAP), as a predictor of
      myocardial oxygen consumption, during the 25-min QS period tended to increase
      with time, but double product remained almost constant during the 25-min PWM
      period. CONCLUSIONS: The results suggest that PWM is effective for suppressing
      cardiocirculatory responses to orthostatic stress.

PMID- 22971905
TI  - Association of CYP2C19 genotype with periprocedural myocardial infarction after
      uneventful stent implantation in Chinese patients receiving clopidogrel
      pretreatment.
AB  - BACKGROUND: High platelet reactivity (HPR) after clopidogrel treatment is linked
      to an increased risk of periprocedural myocardial infarction (PMI). The
      occurrence of PMI that could be associated with CYP2C19 genotype status was our
      hypothesis. METHODS AND RESULTS: A total of 233 patients with non-ST elevation
      acute coronary syndromes (NSTACS) undergoing uneventful elective percutaneous
      coronary intervention were included. Platelet reactivity was assessed by
      thrombelastograph at 24 h after 300 mg clopidogrel loading. HPR was defined as
      >=70% adenosine diphosphate-induced platelet aggregation. The CYP2C19*2 and *3
      loss-of-function (LOF) alleles were determined using DNA microarray method.
      Patients with PMI had significantly higher on-clopidogrel platelet reactivity
      compared to those without PMI (60.0+/-24.4% vs. 43.0+/-24.0%, P<0.001). HPR was
      more frequently observed in patients with PMI and was the strongest risk factor
      of PMI in multivariate analysis (OR(adj)=4.348, 95% CI: 1.846-10.241, P=0.001).
      Furthermore, the incidence of HPR was significantly associated with the carriage
      of 2 CYP2C19 LOF alleles. Compared with non-carriers, patients carrying 2 CYP2C19
      LOF alleles had a 3.000-fold increased risk (95% CI: 1.071-8.400, P=0.037) for
      PMI in multivariate analysis. However, inclusion of HPR as a covariate in the
      regression model changed the significant relationship between the carriage of 2
      CYP2C19 LOF alleles and PMI. CONCLUSIONS: Among Chinese patients with NSTACS,
      carriers with 2 CYP2C19 LOF alleles are more prone to HPR, which is associated
      with an increased risk for PMI.

PMID- 22971906
TI  - Diversity and plasticity of monocyte subsets. Tipping the delicate balance
      involved in the pathogenesis of atherosclerosis.

PMID- 22971907
TI  - Use of a robot for high-throughput crystallization of membrane proteins in
      lipidic mesophases.
AB  - Structure-function studies of membrane proteins greatly benefit from having
      available high-resolution 3-D structures of the type provided through
      macromolecular X-ray crystallography (MX). An essential ingredient of MX is a
      steady supply of ideally diffraction-quality crystals. The in meso or lipidic
      cubic phase (LCP) method for crystallizing membrane proteins is one of several
      methods available for crystallizing membrane proteins. It makes use of a
      bicontinuous mesophase in which to grow crystals. As a method, it has had some
      spectacular successes of late and has attracted much attention with many research
      groups now interested in using it. One of the challenges associated with the
      method is that the hosting mesophase is extremely viscous and sticky, reminiscent
      of a thick toothpaste. Thus, dispensing it manually in a reproducible manner in
      small volumes into crystallization wells requires skill, patience and a steady
      hand. A protocol for doing just that was developed in the Membrane Structural &
      Functional Biology (MS&FB) Group(1-3). JoVE video articles describing the method
      are available(1,4). The manual approach for setting up in meso trials has
      distinct advantages with specialty applications, such as crystal optimization and
      derivatization. It does however suffer from being a low throughput method. Here,
      we demonstrate a protocol for performing in meso crystallization trials
      robotically. A robot offers the advantages of speed, accuracy, precision,
      miniaturization and being able to work continuously for extended periods under
      what could be regarded as hostile conditions such as in the dark, in a reducing
      atmosphere or at low or high temperatures. An in meso robot, when used properly,
      can greatly improve the productivity of membrane protein structure and function
      research by facilitating crystallization which is one of the slow steps in the
      overall structure determination pipeline. In this video article, we demonstrate
      the use of three commercially available robots that can dispense the viscous and
      sticky mesophase integral to in meso crystallogenesis. The first robot was
      developed in the MS&FB Group(5,6). The other two have recently become available
      and are included here for completeness. An overview of the protocol covered in
      this article is presented in Figure 1. All manipulations were performed at room
      temperature (~20  degrees C) under ambient conditions.

PMID- 22971908
TI  - Guidelines on adequate data reporting:  use them!

PMID- 22971909
TI  - How can we explain the gap between randomised studies and 'real life' practice in
      postoperative transfusion triggers? Do we need to change recommended thresholds
      for transfusion?

PMID- 22971910
TI  - Surveys, samplings and botched US presidential election predictions.

PMID- 22971911
TI  - Placental extract improves hippocampal neuronal loss and fear memory impairment
      resulting from chronic restraint stress in ovariectomized mice.
AB  - We have recently found that combination of ovariectomy (OVX) and chronic
      restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons
      in female rats and mice and that estrogen replacement and chronic treatment with
      Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and
      morphological changes. In this study, we examined the effect of placental extract
      on the memory impairment and neuromorphological change in OVX/stress-subjected
      mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle
      treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham
      operated control groups. Two weeks after surgical operation, OVX mice underwent
      restraint stress for 21 days (6 h/day), and all animals were then subjected to a
      contextual fear conditioning test followed by morphological examination by Nissl
      staining. Placental extract was orally administered once daily until the
      behavioral analysis was carried out. Chronic treatment with both doses of
      placental extract improved the OVX/stress-induced fear memory impairment and
      Nissl-positive cell loss of the hippocampal CA3 region, although it did not
      affect the loss of bone mineral density and increase in body weight after OVX.
      These results have important implications for the neuroprotective and cognition
      enhancing effects of placental extract in postmenopausal women.

PMID- 22971912
TI  - Influence of photoactivation method and mold for restoration on the Knoop
      hardness of resin composite restorations.
AB  - The aim of this study was to evaluate in vitro the Knoop hardness in the top and
      bottom of composite photo activated by different methods when different mold
      materials were used. Z250 (3M ESPE) and XL2500 halogen unit (3M ESPE) were used.
      For hardness test, conical restorations were made in extracted bovine incisors
      (tooth mold) and also metal mold (approximately 2 mm top diameter * 1.5 mm bottom
      diameter * 2 mm in height). Different photoactivation methods were tested: high
      intensity continuous (HIC), low-intensity continuous (LIC), soft-start, or pulse
      delay (PD), with constant radiant exposure. Knoop readings were performed on top
      and bottom restoration surfaces. Data were submitted to two-way ANOVA and Tukey's
      test (p = 0.05). On the top, regardless of the mold used, no significant
      difference in the Knoop hardness (Knoop hardness number, in kilograms-force per
      square millimeter) was observed between the photoactivation methods. On the
      bottom surface, the photoactivation method HIC shows higher means of hardness
      than LIC when tooth and metal were used. Significant differences of hardness on
      the top and in the bottom were detected between tooth and metal. The
      photoactivation method LIC and the material mold can interfere in the hardness
      values of composite restorations. 

PMID- 22971914
TI  - Laminated thin-film Teflon chips for petrochemical applications.
AB  - We present Teflon-based microfluidic chips fabricated by laminating multiple
      layers of laser-cut Teflon film. In addition to being solvent-resistant, these
      chips enable simple multilayer fabrication, have uniform rectangular cross
      section and are sufficiently thin to (1) reduce cost, (2) enable rapid
      temperature control, and (3) provide optical transparency. The chips can be
      fabricated without a cleanroom from start to finish in less than 2 h. We
      demonstrate the potential of this approach by measuring the displacement of an
      oil solution by carbon dioxide in a nine-layer thin-film Teflon chip modelling
      porous media. Optical transparency through the 9-layers enables the determination
      of an oil recovery rate. We also demonstrate a thin-film chip measurement of the
      viscosity of heavy oil/toluene mixtures.

PMID- 22971913
TI  - Effects of different surface treatments on shear bond strength in two different
      ceramic systems.
AB  - The purpose of this study was to evaluate the influence of different surface
      treatments (sandblasting, acid etching, and laser irradiation) on the shear bond
      strength of lithium disilicate-based core (IPS Empress 2) and feldspathic
      ceramics (VITA VM 9). One hundred ceramic discs were divided into two groups of
      50 discs each for two ceramic systems: IPS Empress 2 (group I) and VITA VM 9
      (group II). Each of the two groups was further divided into five surface
      treatment groups (ten each) as follows: group SB, sandblasting with alumina
      particles (50 MUm); group HF, 5 % hydrofluoric acid etching; group L, Er:YAG
      laser irradiation (distance, 1 mm; 500 mJ; 20 Hz; 10 W; manually, noncontact R14
      handpiece); group SB-L, sandblasting + Er:YAG laser; and group HF-L, 5 %
      hydrofluoric acid + Er:YAG laser. Luting cement (Panavia 2.0) was bonded to the
      ceramic specimens using Teflon tubes. After 24 h of water storage, a shear bond
      strength test was performed using a universal testing machine at a crosshead
      speed of 0.5 mm/min. The data were analyzed with a two-way analysis of variance
      (ANOVA) and Tukey's honestly significant difference tests (alpha = 0.05). The two
      way ANOVA indicated that the shear bond strength was significantly affected by
      the surface treatment methods (p < 0.05), but there was no significant
      interaction between the ceramic systems. Group SB-L had the highest mean values
      for each ceramic system. Sandblasting, followed by Er:YAG laser irradiation,
      enhanced the bond strength, indicating its potential use as an alternative
      method. The atomic force microscopic evaluation revealed that group SB had the
      most distinct sharp peaks among the groups. 

PMID- 22971915
TI  - Confessions of a JID-lapsed clinician-educator.

PMID- 22971919
TI  - Mimicking hair disorders by genetic manipulation of organ-cultured human hair
      follicles.
AB  - Human hair follicles can be dissected out of scalp skin and cultured in vitro in
      defined growth medium. Hair follicle organ cultures have previously been used to
      investigate the molecular and cellular mechanisms through which various factors
      regulate the maintenance and cycling of adult hair follicles. In this issue,
      Samuelov et al. transfected organ-cultured human hair follicles with siRNA
      nucleotides and suppressed the expression of the endogenous P-cadherin gene in
      follicular keratinocytes. Knocking down the expression of P-cadherin in hair
      follicles in vitro recapitulated the hair follicle phenotype observed in patients
      with hypotrichosis with juvenile macular dystrophy (HJMD) and enabled the authors
      to establish a cause-effect relationship between loss of P-cadherin and
      suppression of the canonical Wnt signaling pathway and upregulation of TGFbeta2
      during development of the hair abnormalities observed in HJMD patients.

PMID- 22971920
TI  - Keratin 71 mutations: from water dogs to woolly hair.
AB  - The study of rare genetic disorders of the hair follicle has resulted in the
      identification of many causative genes, leading to the potential for the
      development of novel therapeutic approaches for both inherited and acquired hair
      disorders. In this issue, Fujimoto et al. identify a missense mutation within the
      keratin 71 (KRT71) gene as the cause for autosomal dominant woolly
      hair/hypotrichosis in a Japanese family. This represents the first human mutation
      in KRT71 to be linked to a hair disorder, establishing this gene as an important
      determinant of mammalian hair texture. Moreover, this finding provides new
      insight into the relationship between similar phenotypes resulting from mutations
      in distinct regulatory pathways and underscores the role of the inner root sheath
      in human hair growth.

PMID- 22971921
TI  - Beyond ABC: another mechanism of drug resistance in melanoma side population.
AB  - It has been shown that a side population (SP), which is characterized by high
      chemical efflux capacity, is present in human melanoma cell lines. However, it
      was not clear whether patients' samples contain the same subpopulation. In this
      issue, Luo et al. (2012) report that they have isolated SP cells directly from
      patients' melanomas. SP cells are resistant to paclitaxel because of the
      upregulation of ABCB1 and ABCB5. Notably, these cells are also resistant to
      temozolomide, which is not a substrate for ATP-Binding Cassette (ABC)
      transporters, in an interleukin (IL)-8-dependent manner. This study provides
      novel clues for understanding how a small, but critical, subpopulation within
      melanomas is resistant to therapies.

PMID- 22971922
TI  - Flow cytometry.

PMID- 22971924
TI  - Tuning the structural coupling between the transmembrane and cytoplasmic domains
      of phospholamban to control sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)
      function.
AB  - Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70
      % of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation
      in humans. Dysfunctions in SERCA:PLN interactions have been implicated as having
      a critical role in cardiac disease, and targeting Ca(2+) transport has been
      demonstrated to be a promising avenue in treating conditions of heart failure.
      Here, we designed a series of new mutants able to tune SERCA function, targeting
      the loop sequence that connects the transmembrane and cytoplasmic helices of PLN.
      We found that a variable degree of loss of inhibition mutants is attainable by
      engineering glycine mutations along PLN's loop domain. Remarkably, a double
      glycine mutation results in a complete loss-of-function mutant, fully mimicking
      the phosphorylated state of PLN. Using nuclear magnetic resonance spectroscopy,
      we rationalized the effects of these mutations in terms of entropic control on
      PLN function, whose inhibitory function can be modulated by increasing its
      conformational dynamics. However, if PLN mutations go past a threshold set by the
      phosphorylated state, they break the structural coupling between the
      transmembrane and cytoplasmic domains, resulting in a species that behaves as the
      inhibitory transmembrane domain alone. These studies provide new potential
      candidates for gene therapy to reverse the effects of heart failure.

PMID- 22971925
TI  - 2D-DIGE proteomic analysis of mesenchymal stem cell cultured on the elasticity
      tunable hydrogels.
AB  - The present study focuses on mechanotransduction in mesenchymal stem cells (MSCs)
      in response to matrix elasticity. By using photocurable gelatinous gels with
      tunable stiffness, proteomic profiles of MSCs cultured on tissue culture plastic,
      soft (3 kPa) and stiff (52 kPa) matrices were deciphered using 2-dimensional
      differential in-gel analysis (2D-DIGE). The DIGE data, tied to
      immunofluorescence, indicated abundance and organization changes in the
      cytoskeletonal proteins as well as differential regulation of important signaling
      related proteins, stress-responsing proteins and also proteins involved in
      collagen synthesis. The major CSK proteins including actin, tubulin and vimentin
      of the cells cultured on the gels were remarkably changed their expressions.
      Significant down-regulation of alpha-tubulin and beta-actin can be observed on
      gel samples in comparison to the rigid tissue culture plates. The expression
      abundance of vimentin appeared to be highest in the MSCs cultured on hard gels.
      These results suggested that the substrate stiffness significantly affects
      expression balances in cytoskeletal proteins of MSCs with some implications to
      cellular tensegrity.

PMID- 22971923
TI  - [Cardiopulmonary bypass in cardiac surgery].
AB  - Cardiopulmonary bypass (CPB) is a standard procedure in cardiac surgery; however,
      apart from its therapeutic options a CPB might also initiate systemic and organ
      specific complications, such as heart failure, renal and pulmonary dysfunction,
      impaired coagulation as well as neurological and cognitive dysfunction. The
      immunological response to the extracorporeal circulation generates systemic
      inflammation which often meets the definition of systemic inflammatory response
      syndrome (SIRS). The main inducers of SIRS are contact of blood with the
      artificial surfaces of the CPB, mechanical stress which affects the blood
      components and the extensive surgical trauma. Hence, a number of technical and
      surgical developments aim at reduction of the inflammatory response caused by the
      CPB. By reason of surgical demands, the majority of cardiothoracic procedures
      still depend on the use of CPB; however, there is an on-going development of new
      techniques trying to reduce the surgical trauma and the negative consequences of
      CPB. Here, minimized systems with biocompatible surfaces have been shown to be
      effective in attenuating the inflammatory response to CPB. Alternative procedures
      such as off-pump surgery may help to avoid CPB-associated complications but due
      to specific limitations will not replace conventional bypass surgery.

PMID- 22971926
TI  - Cytosolic malate dehydrogenase regulates senescence in human fibroblasts.
AB  - Carbohydrate metabolism changes during cellular senescence. Cytosolic malate
      dehydrogenase (MDH1) catalyzes the reversible reduction of oxaloacetate to malate
      at the expense of reduced nicotinamide adenine dinucleotide (NADH). Here, we show
      that MDH1 plays a critical role in the cellular senescence of human fibroblasts.
      We observed that the activity of MDH1 was reduced in old human dermal fibroblasts
      (HDFs) [population doublings (PD) 56], suggesting a link between decreased MDH1
      protein levels and aging. Knockdown of MDH1 in young HDFs (PD 20) and the IMR90
      human fibroblast cell line resulted in the appearance of significant cellular
      senescence features, including senescence-associated beta-galactosidase staining,
      flattened and enlarged morphology, increased population doubling time, and
      elevated p16(INK4A) and p21(CIP1) protein levels. Cytosolic NAD/NADH ratios were
      decreased in old HDFs to the same extent as in MDH1 knockdown HDFs, suggesting
      that cytosolic NAD depletion is related to cellular senescence. We found that AMP
      activated protein kinase, a sensor of cellular energy, was activated in MDH1
      knockdown cells. We also found that sirtuin 1 (SIRT1) deacetylase, a controller
      of cellular senescence, was decreased in MDH1 knockdown cells. These results
      indicate that the decrease in MDH1 and subsequent reduction in NAD/NADH ratio,
      which causes SIRT1 inhibition, is a likely carbohydrate metabolism-controlled
      cellular senescence mechanism.

PMID- 22971927
TI  - Nanoscale investigation of AlGaN/GaN-on-Si high electron mobility transistors.
AB  - AlGaN/GaN HEMTs are devices which are strongly influenced by surface properties
      such as donor states, roughness or any kind of inhomogeneity. The electron gas is
      only a few nanometers away from the surface and the transistor forward and
      reverse currents are considerably affected by any variation of surface property
      within the atomic scale. Consequently, we have used the technique known as
      conductive AFM (CAFM) to perform electrical characterization at the nanoscale.
      The AlGaN/GaN HEMT ohmic (drain and source) and Schottky (gate) contacts were
      investigated by the CAFM technique. The estimated area of these highly conductive
      pillars (each of them of approximately 20-50 nm radius) represents around 5% of
      the total contact area. Analogously, the reverse leakage of the gate Schottky
      contact at the nanoscale seems to correlate somehow with the topography of the
      narrow AlGaN barrier regions producing larger currents.

PMID- 22971928
TI  - Organocatalytic asymmetric syntheses of inthomycins A, B and C.
AB  - The total syntheses of (+)-inthomycin A, (+)-inthomycin B and (-)-inthomycin C,
      the oxazole-triene antibiotics isolated from Streptomyces sp., have been
      accomplished via the highly enantio- and stereoselective construction of the C1
      C7 (iododienyl)aldol units by taking advantage of a Cinchona alkaloid-catalyzed
      asymmetric beta-lactone synthesis and their isomerisation-free Stille coupling
      with (E)-5-(3-(tributylstannyl)allyl)oxazole.

PMID- 22971929
TI  - Renin-angiotensin system modulates neurotransmitters in the paraventricular
      nucleus and contributes to angiotensin II-induced hypertensive response.
AB  - Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses
      contribute to the pathogenesis of hypertension. In this study, we determined
      whether renin-angiotensin system (RAS) activation in the hypothalamic
      paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive
      response via interaction with neurotransmitters in the PVN. Rats underwent
      subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated
      for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS),
      an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG
      II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R
      and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid
      (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial
      pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with
      LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these
      findings suggest that the RAS activation in the PVN contributes to the ANG II
      induced hypertensive response via interaction with PIC and neurotransmitters
      (glutamate, NE and GABA) in the PVN.

PMID- 22971930
TI  - Zebrafish as potential model for developmental neurotoxicity testing: a mini
      review.
AB  - The zebrafish is a powerful toxicity model; biochemical assays can be combined
      with observations at a structural and functional level within one individual.
      This mini review summarises the potency of zebrafish as a model for developmental
      neurotoxicity screening, and its possibilities to investigate working mechanisms
      of toxicants. The use of zebrafish in toxicity research can ultimately lead to
      the refinement or reduction of animal use.

PMID- 22971931
TI  - Urban health challenges in Europe.
AB  - This article synthesizes diverse official reports, statistics, and scientific
      papers that present demographic, economic, environmental, and social trends
      impacting on the health and quality of life of citizens living in European
      cities. A literature review led to the identification of some key challenges
      including an aging society, migration flows, inequalities in health, global
      change, and risk behaviors that should be addressed in order to promote urban
      health. Other challenges, such as food production and consumption, are also
      relevant, but not included. Cities that have participated in one or more of the
      phases of the WHO European Healthy Cities Network have implemented a number of
      policies, programs, and measures to deal with the challenges discussed in this
      article. Some contributions are presented to illustrate how health and quality of
      life in urban areas can be promoted by local authorities. 

PMID- 22971932
TI  - Equity and the social determinants of health in European cities.
AB  - Equity in health has been the underlying value of the World Health Organization's
      (WHO) Health for All policy for 30 years. This article examines how cities have
      translated this principle into action. Using information designed to help
      evaluate phase IV (2003-2008) of the WHO European Healthy Cities Network (WHO
      EHCN) plus documentation from city programs and websites, an attempt is made to
      assess how far the concept of equity in health is understood, the political will
      to tackle the issue, and types of action taken. Results show that although cities
      continue to focus considerable support on vulnerable groups, rather than the full
      social gradient, most are now making the necessary shift towards more upstream
      policies to tackle determinants of health such as poverty, unemployment,
      education, housing, and the environment, without neglecting access to care.
      Although local level data reflecting inequalities in health is improving, there
      is still a long way to go in some cities. The Healthy Cities Project is becoming
      an integral part of structures for long-term planning and intersectoral action
      for health in cities, and Health Impact Assessment is gradually being developed.
      Participation in the WHO-EHCN appears to allow new members to leap-frog ahead
      established cities. However, this evaluation also exposes barriers to effective
      local policies and processes to reduce health inequalities. Armed with locally
      generated evidence of critical success factors, the WHO-EHCN has embarked on a
      more rigorous and determined effort to achieve the prerequisites for equity in
      health. More attention will be given to evaluating the effectiveness of action
      taken and to dealing not only with the most vulnerable but a greater part of the
      gradient in socioeconomic health inequalities. 

PMID- 22971933
TI  - Materials for Healthcare Applications Symposium, EUROMAT 2011 (Montpellier,
      France, 12-15 September 2011).

PMID- 22971934
TI  - Effects of HIV-1 protease on cellular functions and their potential applications
      in antiretroviral therapy.
AB  - Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the
      most potent class of drugs in antiretroviral therapies. However, viral drug
      resistance to PIs could emerge rapidly thus reducing the effectiveness of those
      drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e.,
      inhibitors that compete with substrates for the active enzymatic site. This
      common inhibitory approach increases the likelihood of developing drug resistant
      HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that
      move away from the current target of the active enzymatic site are needed.
      Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic
      activities through non-competitive binding to PR, should be sought. Another
      common feature of current PIs is they were all developed based on the structure
      based design. Drugs derived from a structure-based strategy may generate target
      specific and potent inhibitors. However, this type of drug design can only target
      one site at a time and drugs discovered by this method are often associated with
      strong side effects such as cellular toxicity, limiting its number of target
      choices, efficacy, and applicability. In contrast, a cell-based system may
      provide a useful alternative strategy that can overcome many of the inherited
      shortcomings associated with structure-based drug designs. For example,
      allosteric PIs can be sought using a cell-based system without considering the
      site or mechanism of inhibition. In addition, a cell-based system can eliminate
      those PIs that have strong cytotoxic effect. Most importantly, a simple,
      economical, and easy-to-maintained eukaryotic cellular system such as yeast will
      allow us to search for potential PIs in a large-scaled high throughput screening
      (HTS) system, thus increasing the chances of success. Based on our many years of
      experience in using fission yeast as a model system to study HIV-1 Vpr, we
      propose the use of fission yeast as a possible surrogate system to study the
      effects of HIV-1 protease on cellular functions and to explore its utility as a
      HTS system to search for new PIs to battle HIV-1 resistant strains.

PMID- 22971935
TI  - Electron microscopic structures, serum resistance, and plasmid restructuring of
      New Delhi metallo-beta-lactamase-1 (NDM-1)-producing ST42 Klebsiella pneumoniae
      emerging in Japan.
AB  - Enterobacteriaceae, carrying the New Delhi metallo-beta-lactamase-1 (NDM-1) gene
      (bla (NDM-1)), have emerged and posed a threat since 2006. In Japan, bla (NDM-1)
      carrying Escherichia coli was first described in 2010. In this study, we
      characterized NDM-1-positive Klebsiella pneumoniae strain 419 in Japan, which was
      isolated from the urine of a 90-year-old Japanese patient who had never been to
      the Indian subcontinent. K. pneumoniae 419 belonged to ST42. It possessed a
      surface capsule (with untypeable capsular PCR types) and was resistant to serum
      killing. K. pneumoniae 419 cells were occasionally flagellated or piliated and
      autoaggregated. K. pneumoniae 419 was resistant to beta-lactams (including
      carbapenems), aminoglycosides, and fluoroquinolones, and was susceptible to
      imipenem (or biapenem), aztreonam, polymixin B, and colistin. It possessed at
      least eight plasmids; of those, a 74-kb plasmid (pKPJ1) of the replicon FIIA
      carried bla (NDM-1) and was conjugally transferred to E. coli strains, with a 71
      kb transferable azithromycin-resistant (mphA (+)) plasmid of the replicon F
      (pKPJ2), as a large (145-kb) plasmid (pKPJF100) through a transposition event. In
      addition to bla (NDM-1), pKPJ1 carried arr-2, pKPJ2 carried mphA, and pKPJF100
      carried both. They were negative for the 16S rRNA methylase gene, e.g., which is
      frequently associated with bla (NDM-1). The data demonstrate that K. pneumoniae
      419 possessed virulence- and fitness-associated surface structures, was resistant
      to serum killing, and possessed a unique (or rare) genetic background in terms of
      ST type and bla (NDM-1)-carrying plasmid.

PMID- 22971936
TI  - Pet animals and foreign travel are risk factors for colonisation with extended
      spectrum beta-lactamase-producing Escherichia coli.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of extended
      spectrum beta-lactamase (ESBL) and vancomycin-resistant enterococci (VRE)
      colonisation among healthy infection control personnel and to determine risk
      factors for ESBL or VRE colonisation within this group. METHODS: Participants
      were recruited at an infection control symposium in 2011. Volunteers were asked
      to perform a rectal swab and to fill in questionnaires on risk factors of ESBL or
      VRE carriage (report on diet, contact with domestic or production animals,
      travel, hospital stay and antibiotic use all within the last 12 months). Rectal
      swabs were inoculated onto ESBL and VRE chromogenic agar; species identification
      and susceptibility testing was done by using a VITEK 2 system. In the
      multivariable analysis, a logistic regression with stepwise forward variable
      selection was performed. RESULTS: Two hundred and thirty people participated in
      the study, i.e. 36 % of the symposium attendees (231/639). No VRE faecium or
      faecalis were isolated, whereas ESBL were isolated from 8 out of 231 individuals,
      i.e. 3.5 % (95 % confidence interval 1.5-6.7). In the multivariable analysis,
      travel to Greece or Africa and contact with pets were independently associated
      with ESBL positivity. The odds ratios were as follows: travel to Greece 15.2,
      travel to Africa 14.8 and for having a pet animal 6.7. CONCLUSION: This is the
      first report showing that contact with pets increases by almost seven-fold the
      chance to be colonised with ESBL Escherichia coli. A colonisation rate of 3.5 %
      with ESBL-producing enterobacteriaceae among infection control personnel is of
      concern and reflects probably less an occupational health risk but the reservoir
      of and the expansion into the community, especially in persons with pet animals
      and travel history to high-endemicity countries.

PMID- 22971937
TI  - Successful ganciclovir therapy in a patient with human herpesvirus-6 encephalitis
      after unrelated cord blood transplantation: usefulness of longitudinal
      measurements of viral load in cerebrospinal fluid.
AB  - BACKGROUND: There have been no reports of human herpesvirus-6 (HHV-6)
      encephalitis treatment based on both HHV-6 DNA load and the antiviral agent's
      concentration in the cerebrospinal fluid (CSF). PATIENT: A 20-year-old male with
      a hematological malignancy developed HHV-6 encephalitis 15 days after unrelated
      cord blood transplantation (UCBT). He had fever, chest pain, memory impairment,
      and insomnia. His CSF showed no increased cell counts, but the amount of HHV-6
      DNA was elevated to 2.0 * 10(6) copies/igDNA. Magnetic resonance imaging (MRI) of
      the head revealed abnormal high-intensity signals in the left limbic system on T2
      weighted and diffusion-weighted images. Intravenous administration of ganciclovir
      (GCV) was initiated at 5 mg/kg every 12 h on day 18, and was continued until day
      137. The amount of HHV-6 DNA in the plasma became undetectable on day 25. The HHV
      6 load in the CSF decreased to 1.5 * 10(3) copies/igDNA on day 32, and reached
      undetectable levels on day 53. The mean concentration of GCV 1 h after an
      infusion of 5 mg/kg was 4.12 mg/mL in plasma and 0.7 mg/mL in CSF. The chest pain
      and insomnia disappeared on days 35 and 47, respectively. Memory defects
      recovered up to day 85. CONCLUSION: Serial quantification of HHV-6 DNA in CSF may
      be useful for successful treatment with GCV in post-transplant HHV-6
      encephalitis.

PMID- 22971938
TI  - Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected
      patients in the HAART era?
AB  - PURPOSE: The objective of our study was to evaluate the presence of respiratory
      symptoms and chronic obstructive pulmonary disease (COPD) in a human
      immunodeficiency virus (HIV)-infected outpatient population and to further
      investigate the role of highly active antiretroviral therapy (HAART) and other
      possibly associated risk factors. METHODS: We consecutively enrolled in a cross
      sectional study HIV-infected patients and HIV-negative age, sex and smoking
      status matched controls. All participants completed a questionnaire for pulmonary
      symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV
      infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected
      patients had a significantly higher prevalence of any respiratory symptom (p =
      0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had
      a significantly higher prevalence of COPD in respect of HIV-negative controls (p
      = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002)
      lower forced expiratory volume at one second (FEV1) and FEV1/forced vital
      capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung
      capacity (TLC) was significantly higher (p = 0.018). In the multivariate
      analysis, significant predictors of respiratory symptoms were current smoking
      [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and
      previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only
      significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96).
      HAART receipt was not associated with respiratory symptoms nor with COPD.
      CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD
      among HIV-infected patients. HIV infection, current cigarette smoking and
      previous bacterial pneumonia seem to play a significant role in the development
      of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk
      HIV-infected patients should be screened for COPD to early identify those who may
      need specific treatment.

PMID- 22971939
TI  - Endogenous nitric oxide generation in protoplast chloroplasts.
AB  - KEY MESSAGE : NO generation is studied in the protoplast chloroplasts. NO, ONOO (
      - ) and ROS (O ( 2 ) ( - ) and H ( 2 ) O ( 2 ) ) are generated in chloroplasts.
      Nitric oxide synthase-like protein appears to be involved in NO generation.
      Nitric oxide stimulates chlorophyll biosynthesis and chloroplast differentiation.
      The present study was conducted to better understand the process of NO generation
      in the leaf chloroplasts and protoplasts. NO, peroxynitrite and superoxide anion
      were investigated in the protoplasts and isolated chloroplasts using specific
      dyes, confocal laser scanning and light microscopy. The level of NO was highest
      after protoplast isolation and subsequently decreased during culture. Suppression
      of NO signal in the presence of PTIO, suggests that diaminofluorescein-2
      diacetate (DAF-2DA) detected NO. Detection of peroxynitrite, a reaction product
      of NO and superoxide anion, further suggests NO generation. Moreover, generation
      of NO and peroxynitrite in the chloroplasts of wild-type Arabidopsis and their
      absence or weak signals in the leaf-derived protoplasts of Atnoa1 mutants
      confirmed the reactivity of DAF-2DA and aminophenyl fluorescein to NO and
      peroxynitrite, respectively. Isolated chloroplasts also showed signal of NO.
      Suppression of NO signal in the presence of 100 MUM nitric oxide synthase
      inhibitors [L-NNA, Nomega-nitro-L-arginine and PBIT, S,S'-1,3-phenylene-bis(1,2
      ethanediyl)-bis-isothiourea] revealed that nitric oxide synthase-like system is
      involved in NO synthesis. Suppression of NO signal in the protoplasts isolated in
      the presence of cycloheximide suggests de novo synthesis of NO generating protein
      during the process of protoplast isolation. Furthermore, the lack of inhibition
      of NO production by sodium tungstate (250 MUM) and inhibition by L-NNA, and PBIT
      suggest involvement NOS-like protein, but not nitrate reductase, in NO generation
      in the leaf chloroplasts and protoplasts.

PMID- 22971940
TI  - Metabolic syndrome influencing infarct size and heart failure in patients with
      acute coronary syndrome: does gender matter?
AB  - Metabolic syndrome (MetS) is the occurrence of diabetes mellitus/glucose
      intolerance, arterial hypertension, central obesity, dyslipidemia, and
      microalbuminuria in the same patient (definition by WHO).  Presence of metabolic
      syndrome is associated with larger myocardial infarction size and complications
      following acute myocardial infarction.  Two hundred and thirty patients with
      acute coronary syndromes were analyzed.  Those with MetS (n=141) included
      patients with diabetes mellitus/glucose intolerance and at least two of the
      following criteria: hypertension, hypertriglyceridemia/low HDL cholesterol,
      android obesity/body mass index (BMI) >= 30, or microalbuminuria.  Control group
      did not meet criteria for MetS.  Presence of heart failure was assigned according
      to Killip classification.  The MetS group had larger myocardial infarction size
      determined by peak creatine-kinase (CK) (1484+/-1354 vs. 981+/-890, p = 0.003)
      and CK MB (141+/-117 vs. 95+/-78, p = 0.002).  While in non-MetS group males had
      larger myocardial infarction than females, in MetS group females had larger
      myocardial infarction than males.  Cardiac failure occurred more in MetS group of
      patients, again was more prominent in females.  Occurrence of metabolic syndrome
      in acute coronary syndrome patients predisposes to larger myocardial infarction
      size, more on the account of female patients having MetS.  MetS, again
      particularly in females, predisposes to higher chance of having heart failure
      during acute coronary syndrome.  Recognizing the female group with MetS as of
      higher risk for large myocardial infarction and heart failure leads us to pay
      special attention on this patient population.

PMID- 22971941
TI  - Annexin A5 protein expression is associated with the histological differentiation
      of uterine cervical squamous cell carcinoma in patients with an increased serum
      concentration.
AB  - Annexin A5 (ANXA5) is a calcium-dependent phospholipid-binding protein belonging
      to the annexin family and is expressed abnormally in several types of carcinoma.
      In the present study, ANXA5 protein expression was evaluated by western blot
      analysis in a series of 60 human uterine cervical squamous cell carcinomas
      (UCSCCs) to search for molecular alterations that may be able to serve as useful
      diagnostic/prognostic markers. The upregulation of ANXA5 expression was observed
      in 48/60 UCSCC cases (80%), whereas a weak expression was observed in the 25
      normal uterine cervical tissues. ANXA5 expression was also analyzed by
      immunohistochemical staining, western blot and reverse transcription-polymerase
      chain reaction (RT-PCR) assays of the UCSCC and uterine cervical normal tissue
      lesions. All dysplastic tissues showed significantly increased ANXA5 expression
      compared with the weak signal observed in normal epithelia. A close association
      was observed between the ANXA5 expression levels and the histological grade of
      UCSCC. Compared with moderately and well-differentiated tumors, there was a
      significant increase in ANXA5 expression in poorly differentiated tumors.
      Furthermore, ANXA5 concentrations in the blood serum of the patients were
      significantly increased. Our findings clearly identify ANXA5 as an effective
      differentiation marker for the histopathological grading of UCSCCs and for the
      detection of epithelial dysplasia. The results from our study support the
      critical role of ANXA5 in the molecular profiling of UCSCC.

PMID- 22971942
TI  - Harvesting and cryo-cooling crystals of membrane proteins grown in lipidic
      mesophases for structure determination by macromolecular crystallography.
AB  - An important route to understanding how proteins function at a mechanistic level
      is to have the structure of the target protein available, ideally at atomic
      resolution. Presently, there is only one way to capture such information as
      applied to integral membrane proteins (Figure 1), and the complexes they form,
      and that method is macromolecular X-ray crystallography (MX). To do MX
      diffraction quality crystals are needed which, in the case of membrane proteins,
      do not form readily. A method for crystallizing membrane proteins that involves
      the use of lipidic mesophases, specifically the cubic and sponge phases(1-5), has
      gained considerable attention of late due to the successes it has had in the G
      protein-coupled receptor field(6-21) (www.mpdb.tcd.ie). However, the method,
      henceforth referred to as the in meso or lipidic cubic phase method, comes with
      its own technical challenges. These arise, in part, due to the generally viscous
      and sticky nature of the lipidic mesophase in which the crystals, which are often
      micro-crystals, grow. Manipulating crystals becomes difficult as a result and
      particularly so during harvesting(22,23). Problems arise too at the step that
      precedes harvesting which requires that the glass sandwich plates in which the
      crystals grow (Figure 2)(24,25) are opened to expose the mesophase bolus, and the
      crystals therein, for harvesting, cryo-cooling and eventual X-ray diffraction
      data collection. The cubic and sponge mesophase variants (Figure 3) from which
      crystals must be harvested have profoundly different rheologies(4,26). The cubic
      phase is viscous and sticky akin to a thick toothpaste. By contrast, the sponge
      phase is more fluid with a distinct tendency to flow. Accordingly, different
      approaches for opening crystallization wells containing crystals growing in the
      cubic and the sponge phase are called for as indeed different methods are
      required for harvesting crystals from the two mesophase types. Protocols for
      doing just that have been refined and implemented in the Membrane Structural and
      Functional Biology (MS&FB) Group, and are described in detail in this JoVE
      article (Figure 4). Examples are given of situations where crystals are
      successfully harvested and cryo-cooled. We also provide examples of cases where
      problems arise that lead to the irretrievable loss of crystals and describe how
      these problems can be avoided. In this article the Viewer is provided with step
      by-step instructions for opening glass sandwich crystallization wells, for
      harvesting and for cryo-cooling crystals of membrane proteins growing in cubic
      and in sponge phases.

PMID- 22971943
TI  - Evaluation of tissue blood flow of the gastric tube after vessel anastomosis  for
      esophageal reconstruction.
AB  - OBJECTIVES AND METHODS: Impaired blood flow of the upper end of the gastric tube
      is one of the major causes of anastomotic leak following esophageal
      reconstruction after esophagectomy for cancer. We applied an additional
      microvascular anastomosis procedure--the supercharging technique--to improve
      blood flow. We investigated blood flow improvement in 15 patients who underwent
      the supercharging technique after total excision of the thoracic esophagus and
      gastric tube reconstruction through the posterior mediastinal route from August
      2003 to March 2005. RESULTS: Tissue blood flow was measured with laser Doppler
      flowmetry during surgery and was improved after microvascular anastomosis.
      Patency and blood flow of anastomosed arteries were evaluated with computed
      tomography and ultrasonography, respectively. Patency and stable blood flow of
      anastomosed arteries were confirmed more than 1 month after surgery. Therefore,
      microvascular anastomosis improved the tissue blood flow of the upper end of the
      gastric tube. Long-term blood flow improvement was confirmed, which suggests that
      microvascular anastomosis contributes to reducing the risk of anastomotic leak.

PMID- 22971944
TI  - Long-term stabilization of respiratory conditions in patients with spinal
      muscular atrophy  type 2 by continuous positive airway pressure: a report of two
      cases.
AB  - Spinal muscular atrophy (SMA) type 2 is a motor neuron disease that leads to
      severe congenital muscle atrophy. The majority of adult patients are at risk of
      death due to respiratory failure. Here, we report on two patients with SMA type 2
      who repeatedly developed bronchitis and pneumonia. The patient in Case 1 was a 48
      year-old female lacking exon 7 of the survival motor neuron gene (SMN) 1. The
      patient in Case 2 was a 37-year-old female lacking exons 7 and 8 in SMN 1 and
      exon 5 in the neuronal apoptosis inhibitory protein (NAIP) gene. We applied
      continuous positive airway pressure (CPAP) in both cases because their data on
      polysomnography showed obstructive sleep apnea (OSA). CPAP treated their
      respiratory symptoms as well as those due to OSA. Moreover, CPAP stabilized the
      respiratory condition of Case 1 for seven years and seven months and that of Case
      2 for five years and four months. These findings suggest that CPAP alone can
      achieve long-term improvement in the respiratory condition in patients with SMA
      type 2.

PMID- 22971945
TI  - A modified simple questionnaire to estimate dietary energy intake for the
      Japanese.
AB  - To produce a simple food questionnaire for estimating total energy intake and
      intake of  three major nutrients which medical or health care staff such as
      nurses can rapidly use for the  determination of health guidance for individuals.
      The study group comprised 116 normal healthy subjects (mean age +/- S.D. = 40.0
      +/- 17.8 years),  76 women and 40 men. Using findings based on our previous
      research and experiences and the simple  food questionnaire (MHW-FQ) that the
      "Kenkoh Shihyoh Sakutei Iinkai" established by the then  Ministry of Health and
      Welfare developed in 1975, we produced a modified version of the MHW-FQ  and
      named it M-MHW-FQ. The study presented here was conducted for the statistical
      determination of  the usefulness of M-MHW-FQ. M-MHW-FQ yielded much better
      results than MHW-FQ as evidenced by improved correlation coefficients,  which
      ranged between 0.56 and 0.75. The findings showed that, despite its simplicity, M
      MHW-FQ yielded  relatively accurate results and was satisfactory for the rapid
      estimation of total energy intake including  that of three major nutrients. This
      study provides evidence that our simple questionnaire, M-MHW-FQ, is useful for
      the rapid estimation  of individual total dietary energy intake and nutrient
      balance. We expect that our questionnaire can make  a significant contribution to
      an improvement in lifestyle-related diseases.

PMID- 22971946
TI  - Characteristics of influenza virus genome mutations.
AB  - Although the viral factors of host adaptation from domestic poultry to humans
      have been  studied several times since the first cases of direct transmission of
      highly pathogenic avian influenza  viruses from domestic poultry to humans were
      confirmed in 1997, the host-specific adaptation mechanisms  from waterfowl to
      domestic poultry remain unknown.  To study the mechanisms involved, a waterfowl
      derived  virus was passaged in a chicken fibroblast cell line.  This passaged
      virus was found to have much higher  growth titer than that of the original virus
      and several mutations were discovered in its genome.  One of  the most
      characteristics was an increase of the polymorphism of the internal genes.  In
      addition, the general  applicability of this property to the field isolates of
      influenza A viruses by database sequences analysis  was confirmed, with the
      smallest amount of amino acid polymorphism in viral internal proteins observed in
      waterfowl-derived viruses, more in domestic poultry and the most in human
      derived viruses. Although specific  amino acid changes conserved in human-derived
      viruses were found, such amino acid changes were not observed  in poultry-derived
      viruses.

PMID- 22971947
TI  - Smoking promotes subclinical atherosclerosis in apparently healthy men: 2-year
      ultrasonographic follow-up.
AB  - BACKGROUND: Smoking is a major risk factor for cardiovascular disease. Also,
      inflammatory activation and metabolic disorder are the mediators of smoking
      induced atherosclerotic progression. The aim of the present study was to
      investigate whether current smoking and smoking cessation alter inflammatory or
      metabolic status and affect subclinical atherosclerosis in apparently healthy
      men. METHODS AND RESULTS: Classical risk factors and smoking habit were evaluated
      in 354 men who completed health examinations annually without any current
      medications. Carotid intima-media thickness (IMT) was followed for 27.1+/-4.5
      months. At baseline, both maximum and mean IMT significantly changed during 2
      year follow-up. They tended to increase along with progression of smoking habit,
      with significantly greater maximum IMT in current smokers compared with never
      smokers. Both maximum and mean IMT significantly changed during 2-year follow-up,
      and tended to increase with progression of smoking habit, with maximum IMT being
      greatest for current smokers. Past smokers tended to have greater IMT increase
      than never smokers. Among smoking habit and some atherosclerotic risk markers
      that showed significant correlation with maximum IMT increase, stepwise
      regression showed that smoking habit and serum low-density lipoprotein
      cholesterol (LDL-C) level were the only independent predictors. CONCLUSIONS:
      Significant 2-year progression of subclinical atherosclerosis was associated with
      continuous smoking and LDL-C. This was only partly moderated in past smokers
      despite complete reversal of inflammatory activation, suggesting another crucial
      factor for inhibiting accelerated progression of subclinical atherosclerosis in
      men.

PMID- 22971948
TI  - Blood urea nitrogen as an integrated biomarker for hospitalized heart failure.

PMID- 22971949
TI  - Quantitative optical frequency domain imaging assessment of in-stent structures
      in patients with ST-segment elevation myocardial infarction: impact of imaging
      sampling rate.
AB  - BACKGROUND: The impact of the sampling rate (SR) of optical frequency domain
      imaging (OFDI) on quantitative assessment of in-stent structures (ISS) such as
      plaque prolapse and thrombus remains unexplored. METHODS AND RESULTS: OFDI after
      stenting was performed in ST-segment elevation myocardial infarction (STEMI)
      patients using a TERUMO OFDI system (Terumo Europe, Leuven, Belgium) with 160
      frames/s and pullback speed of 20 mm/s. A total of 126 stented segments were
      analyzed. ISS were classified as either attached or non-attached to stent area
      boundaries. The volume, mean area and largest area of ISS were assessed according
      to 4 frequencies of SR, corresponding to distances between the analyzed frames of
      0.125, 0.25, 0.50 and 1.0 mm. ISS volume was calculated by integrating cross
      sectional ISS areas multiplied by each sampling distance using the disk summation
      method. The volume and mean area of ISS became significantly larger, while the
      largest area became significantly smaller as sampling distance became larger
      (1.11 mm(2) for 0.125 mm vs. 1.00 mm(2) for 1.0 mm, P for trend=0.036). In
      addition, variance of difference was positively associated with increasing width
      of sampling distance. CONCLUSIONS: Quantification of ISS is significantly
      influenced by the applied frequency of SR. This should be taken into account when
      designing future OFDI studies in which quantitative assessment of ISS is critical
      for the evaluation of STEMI patients.

PMID- 22971950
TI  - Disease surveillance system evaluation as a model for improved integration and
      standardization of the laboratory component in the Field Epidemiology and
      Laboratory Training Program (FELTP) curriculum worldwide.
AB  - Integration of laboratory training into the Centers for Disease Control and
      Prevention's (CDC) Field Epidemiology Training Program (FETP) began in 2004 and
      has advanced the training of laboratory scientists worldwide on the basic
      principles of epidemiology, disease surveillance, and outbreak investigation. The
      laboratory component of the FE(L)TP training has traditionally been disease
      specific, revolving around classroom and bench training on laboratory methods,
      and field placement in areas where services are needed. There is however a need
      to improve the integration of epidemiology elements used in surveillance,
      outbreak investigation, and evaluation activities with specific measurable
      laboratory activities that could in turn impact the overall disease surveillance
      and response. A systematic and clear evaluation guideline for the laboratory
      components of disease surveillance systems alongside the corresponding
      epidemiological indicators can better identify, address, and mitigate weaknesses
      that may exist in the entire surveillance system, and also help to integrate and
      standardize the FE(L)TP curriculum content. The institution of laboratory Quality
      Management System principles linked to a comprehensive surveillance evaluation
      scheme will result in improved disease surveillance, response, and overall
      laboratory capacity over time.

PMID- 22971951
TI  - Adrenal venous catecholamine concentrations in patients with adrenal masses other
      than pheochromocytoma.
AB  - The aim of this study was to retrospectively examine adrenal venous catecholamine
      concentrations and related indices in non-pheochromocytoma patients and to
      estimate from the obtained results whether measurements of adrenal venous
      catecholamine concentrations by adrenal venous sampling (AVS) are useful for
      localizing adrenal pheochromocytoma. The study population comprised 15 patients
      in whom AVS was performed for evaluation of adrenal non-pheochromocytoma masses
      (primary aldosteronism, n = 8; Cushing syndrome, n = 5; non-hyperfunctioning
      tumor, n = 2) without hormonal intervention and was successful in bilaterally
      judging adrenal vein to infra-renal inferior vena cava cortisol ratios as >3.0.
      Wide ranges of catecholamine concentrations were seen for both right
      (epinephrine, 35-175,821 pg/ml; norepinephrine, 115-32,102 pg/ml; dopamine, 9-232
      pg/ml) and left (epinephrine, 16-27,251 pg/ml; norepinephrine, 155-9,267 pg/ml;
      dopamine, 5-234 pg/ml) adrenal veins. High- to low-side adrenal vein
      concentration ratios also showed wide ranges of up to 779 for epinephrine, 22.5
      for norepinephrine, and 7.8 for dopamine. Adrenal venous catecholamine
      concentrations obtained by AVS and simple comparisons between bilateral adrenal
      veins might not be useful to localize adrenal pheochromocytoma, as wide
      variations in concentrations and high- to low-side adrenal vein concentration
      ratios were noted in patients with adrenal non-pheochromocytoma.

PMID- 22971953
TI  - A comparative physico-chemical study of chlorapatite and hydroxyapatite: from
      powders to plasma sprayed thin coatings.
AB  - Due to their bioactivity and osteoconductivity, hydroxyapatite (HA) plasma
      sprayed coatings have been widely developed for orthopedic uses. However, the
      thermodynamic instability of HA leads frequently to a mixture of phases which
      limit the functional durability of the coating. This study investigates the
      plasma spraying of chlorapatite (ClA) powder, known to melt without
      decomposition, onto pure titanium substrates using a low energy plasma spray
      system (LEPS). Pure ClA powder was prepared by a solid gas reaction at 950 
      degrees C and thermogravimetric analysis showed the good thermal stability of ClA
      powder in the range 30-1400  degrees C compared to that of the HA powder.
      Characterization of ClA coating showed that ClA had a very high crystalline ratio
      and no other crystalline phase was detected in the coating. HA and ClA coatings
      composition, microstructure and in vitro bioactivity potential were studied,
      compared and discussed. In vitro SBF test on HA and ClA coatings revealed the
      formation of a poorly crystalline apatite on the coating surface suggesting that
      we could expect a good osteoconductivity especially for the ClA coating prepared
      by the LEPS system.

PMID- 22971952
TI  - Inhibitory function of parathyroid hormone-related protein on chondrocyte
      hypertrophy: the implication for articular cartilage repair.
AB  - Cartilage repair tissue is usually accompanied by chondrocyte hypertrophy and
      osseous overgrowths, and a role for parathyroid hormone-related protein (PTHrP)
      in inhibiting chondrocytes from hypertrophic differentiation during the process
      of endochondral ossification has been demonstrated. However, application of PTHrP
      in cartilage repair has not been extensively considered. This review systemically
      summarizes for the first time the inhibitory function of PTHrP on chondrocyte
      hypertrophy in articular cartilage and during the process of endochondral
      ossification, as well as the process of mesenchymal stem cell chondrogenic
      differentiation. Based on the literature review, the strategy of using PTHrP for
      articular cartilage repair is suggested, which is instructive for clinical
      treatment of cartilage injuries as well as osteoarthritis. 

PMID- 22971954
TI  - [Cortisone-induced humerus head necrosis in acute myeloid leukemia: cartilage
      preserving arthroscopic spongioplasty].
AB  - Osteonecrosis is a long known side effect in patients receiving cortisone or
      chemotherapy. A young patient was diagnosed with acute myeloid leukemia (AML) in
      2005. After receiving combined cortisone and chemotherapy the patient was in
      complete remission. In 2007 a total hip replacement was necessary due to femoral
      head necrosis. Years after the joint replacement the patient reported acute
      shoulder pain without trauma. In this article an alternative procedure to an
      endoprothesis in a young patient with a humeral head osteonecrosis is presented.

PMID- 22971956
TI  - Environmental photostability of SF6-etched silicon nanocrystals.
AB  - We report on the long-term environmental stability of the photoluminescent (PL)
      properties of silicon nanocrystals (SiNCs). We prepared sulfur hexafluoride
      (SF(6)) etched SiNCs in a two-stage plasma reactor and investigated their PL
      stability against UV irradiation in air. Unlike SiNCs with hydrogen-passivated
      surfaces, the SF(6)-etched SiNCs exhibit no photobleaching upon extended UV
      irradiation despite surface oxidation. Furthermore, the PL quantum yield also
      remains stable upon heating the SF(6)-etched SiNCs up to 160  degrees C. The
      observed thermal and UV stability of SF(6)-etched SiNCs combined with their PL
      quantum yields of up to ~50% make them attractive candidates for UV downshifting
      to enhance the efficiency of solar cells. Electron paramagnetic spin resonance
      indicates that the SF(6)-etched SiNCs have a lowered density of defect states,
      both as-formed and after room temperature oxidation in air.

PMID- 22971955
TI  - [The TraumaRegister DGU(r) as the basis of medical quality management. Ten years
      experience of a national trauma centre exemplified by emergency room treatment].
AB  - BACKGROUND: The trauma register of the German Society of Trauma Surgery
      (TraumaRegister DGU(r)/TR-DGU) has been proven to be a valuable tool for external
      assessment of quality in the treatment of patients with major trauma. This
      publication shows for the first time how the quality of trauma treatment in a
      level I trauma centre could be improved over a period of almost ten years with
      the help of continuous quality management, i.e. recognizing a problem, developing
      a solution and evaluating its effect. MATERIALS AND METHODS: Tracer parameters
      and indicators of quality are presented in four periods over a total study period
      from 1st January 1989 to 31st March 2007. The division into four periods is due
      to major changes in the trauma treatment algorithms or structural changes in the
      trauma room. The results are displayed for all patients treated in the trauma
      room and for those patients with an injury severity score (ISS)>=16. RESULTS:
      Over all four periods a total number of n=2,239 patients were admitted to the
      trauma room. Based on the results of the trauma register a number of changes were
      made, not only structural changes, such as the introduction of point-of-care
      diagnostics, initially conventional X-ray, then digital X-ray and finally
      multislice computed tomography (CT) scanning in the trauma room but also changes
      in the way personnel participating in the trauma treatment are trained. Advanced
      trauma life support (ATLS(r)) has become the standard training for doctors and
      prehospital trauma life support (PHTLS(r)) for nurses. Time efficient treatment
      algorithms were introduced. All measures led to changes in several parameters
      which are chosen as indicators for good treatment quality. It was for instance
      possible to reduce the average total trauma treatment time for patients with an
      ISS>=16 from initially 90.9+/-48.6 min to 37.4+/-18.  min in the final study
      period. CONCLUSIONS: The external quality management performed by the TR-DGU has
      proved to be a constant source of inspiration. The effects of the changes made
      can be scientifically proven. It is to be discussed to what extent a sole
      external quality management can be useful.

PMID- 22971957
TI  - Sustained high plasma mannose less sensitive to fluctuating blood glucose in
      glycogen storage disease type Ia children.
AB  - Plasma mannose is suggested to be largely generated from liver glycogen-oriented
      glucose-6-phosphate. This study examined plasma mannose in glycogen storage
      disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in
      the liver. We initially examined fasting--and postprandial 2 h--plasma mannose
      and other blood carbohydrates and lipids for seven GSD Ia children receiving
      dietary interventions using cornstarch and six healthy age-matched children.
      Next, one-day successive intra-individual parameter changes were examined for six
      affected and two control children. Although there were no significant differences
      in fasting--and postprandial 2 h--glucose and insulin levels, the mannose level
      of the affected group was invariably much higher than that of the control group
      (p < 0.001): the fasting level of the affected group was about two-fold that of
      the control group; the postprandial-2 h level remained almost unchanged in the
      affected group, although it was one-half of the fasting level in the control
      group. Inter-individual analyses revealed that the GSD Ia group mannose level was
      significantly and positively correlated with lactate and triglycerides levels at
      both time points (p < 0.01). In each control, mannose levels fluctuated greatly,
      maintaining strong and significant negative correlations with glucose and insulin
      levels (p < 0.001). Correlations were lower or nonexistent in GSD Ia children. In
      individuals with high lactate and triglycerides levels, strikingly high mannose
      levels never changed against glucose and insulin fluctuations. Plasma mannose is
      less sensitive to blood glucose and insulin in GSD Ia children. Its basal level
      and the fluctuation pattern differ by their metabolic activity.

PMID- 22971958
TI  - Low lysine diet in glutaric aciduria type I--effect on anthropometric and
      biochemical follow-up parameters.
AB  - BACKGROUND: Metabolic treatment in glutaric aciduria type I (GA-I) including a
      low lysine diet with lysine-free, tryptophan-reduced amino acid supplements
      (AAS), carnitine supplementation and early start of emergency treatment during
      putatively threatening episodes of intermittent febrile illness dramatically
      improves the outcome and thus has been recommended by an international guideline
      group (Kolker et al, J Inherit Metab Dis 30:5-22, 2007). However, possible
      affection of linear growth, weight gain and biochemical follow-up monitoring has
      not been studied systematically. METHODS: Thirty-three patients (n = 29
      asymptomatic, n = 4 dystonic) with GA-I who have been identified by newborn
      screening in Germany from 1999 to 2009 were followed prospectively during the
      first six years of life. Dietary treatment protocols, anthropometrical and
      biochemical parameters were longitudinally evaluated. RESULTS: Mean daily intake
      as percentage of guideline recommendations was excellent for lysine (asymptomatic
      patients: 101 %; dystonic patients: 103 %), lysine-free, tryptophan-reduced AAS
      (108 %; 104 %), energy (106 %; 110 %), and carnitine (92 %; 102 %). Low lysine
      diet did not affect weight gain (mean SDS 0.05) but mildly impaired linear growth
      in asymptomatic patients (mean SDS -0.38), while dystonic patients showed
      significantly reduced weight gain (mean SDS -1.32) and a tendency towards linear
      growth retardation (mean SDS -1.03). Patients treated in accordance with recent
      recommendations did not show relevant abnormalities of routine biochemical follow
      up parameters. INTERPRETATION: Low lysine diet promotes sufficient intake of
      essential nutrients and anthropometric development in asymptomatic children up to
      age 6 year, whereas individualized nutritional concepts are required for dystonic
      patients. Revised recommendations for biochemical monitoring might be required
      for asymptomatic patients.

PMID- 22971959
TI  - Pharmacological read-through of nonsense ARSB mutations as a potential
      therapeutic approach for mucopolysaccharidosis VI.
AB  - Mucopolysaccharidosis type VI (MPS VI) is a severe lysosomal storage disorder
      without central nervous system involvement caused by arylsulfatase B (ARSB)
      deficiency. MPS VI is characterized by dysostosis multiplex, corneal clouding,
      heart valve defects and urinary excretion of glycosaminoglycans (GAGs). The
      current treatment for MPS VI is enzyme replacement therapy (ERT) which has
      limited efficacy on bone, joints and heart valve disease, as well as high costs.
      A potential therapeutic approach for the subgroup of MPS VI patients that carry
      nonsense mutations is to enhance stop-codon read-through, using small molecules,
      to restore production of the full-length ARSB protein. In this study we
      investigated whether two compounds known to induce stop codon read-through, the
      aminoglycoside gentamicin and PTC124, can promote read-through of four different
      ARSB nonsense mutations (p.R315X, p.R327X, p.Q456X and p.Q503X) associated with
      MPS VI and enable the synthesis of full-length functional ARSB protein in
      patients fibroblast cell lines. Our study demonstrates that PTC124 but not
      gentamicin, increases the level of ARSB activity in three MPS VI patient
      fibroblast cell lines. In two of them the levels of ARSB activity obtained were
      significantly higher than in untreated cells, reaching <=2.5 % of those detected
      in wild-type fibroblasts and resulting in significant reduction of lysosomal
      size. Since even small increases in enzyme activity can dramatically influence
      the clinical phenotype of MPS VI, our study suggests that pharmacological read
      through may be combined with ERT potentially increasing therapeutic efficacy in
      those patients bearing nonsense ARSB mutations.

PMID- 22971960
TI  - Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse
      models for mucopolysaccharidosis type I, IIIA, IVA, and VII.
AB  - Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by
      mutations in lysosomal enzymes involved in degradation of glycosaminoglycans
      (GAGs). Patients with MPS grow poorly and become physically disabled due to
      systemic bone disease. While many of the major skeletal effects in mouse models
      for MPS have been described, no detailed analysis that compares GAGs levels and
      characteristics of bone by micro-CT has been done. The aims of this study were to
      assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA
      and VII), to determine the relationship between severity of bone dysplasia and
      serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and
      to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models.
      Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and
      IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone
      dysplasia, higher bone mineral density, narrowed spinal canal, and shorter
      sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated
      in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT,
      radiographs and histopathology correlated with the level of KS elevation. We
      showed that elevated HS levels in MPS mouse models could inhibit N
      acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS
      could be released from chondrocytes affected by accumulation of other GAGs and
      that KS could be useful as a biomarker for severity of bone dysplasia in MPS
      disorders.

PMID- 22971962
TI  - Corrole isomers: intrinsic gas-phase shapes via traveling wave ion mobility mass
      spectrometry and dissociation chemistries via tandem mass spectrometry.
AB  - Corrole and four of its isomers with subtle structural changes promoted by
      exchange of nitrogen and carbon atoms in the corrole ring have been studied by
      traveling wave ion mobility mass spectrometry and collision induced dissociation
      experiments. Significant differences in shapes and charge distributions for their
      protonated molecules were found to lead to contrasting gas phase mobilities, most
      particularly for corrorin, the most "confused" isomer. Accordingly, corrorin was
      predicted by B3LYP/6-31g(d,p) and collisional cross section calculations to
      display the most compact tri-dimensional structure, whereas NCC4 and corrole were
      found to be the most planar isomers. Better resolution between the corrole
      isomers was achieved using the more polarizable and massive CO(2) as the drift
      gas. Sequential losses of HF molecules were found to dominate the dissociation
      chemistry of the protonated molecules of these corrole isomers, but their unique
      structures caused contrasting labilities towards CID, whereas NCC4 showed a
      peculiar and structurally diagnostic loss of NH(3), allowing its prompt
      differentiation from the other isomers.

PMID- 22971961
TI  - Letter to the editor re: spectral Hounsfield units--a new radiological concept.

PMID- 22971963
TI  - Primary membranoproliferative glomerulonephritis on the decline: decreased rate
      from the 1970s to the 2000s in Japan.
AB  - BACKGROUND: A prolonged change in the rate of primary membranoproliferative
      glomerulonephritis (MPGN) was identified using a Japanese database of renal
      biopsies. METHODS: We retrospectively investigated 6,369 renal biopsies that were
      performed between 1976 and 2009. Primary MPGN patients were selected, and the
      clinical and pathological findings were examined. We also statistically analyzed
      the changing rate of the onset of primary MPGN according to each decade. RESULTS:
      Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed.
      The age of the patients ranged from 6-79 years (average 34.6 years). There were
      24 children and 55 adults, including 37 male and 42 female patients. Thirty-six
      cases of primary MPGN (45.6 %) showed nephrotic syndrome-8 childhood and 28 adult
      cases. In the pathological classification of 44 samples using electron
      microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were
      MPGN type III. The secular change of the rate of primary MPGN onset showed a
      statistically significant reduction from the 1970s to the 2000s. The rate of
      primary MPGN onset in the child population also significantly decreased, but not
      in the adult population. Among the clinical parameters, disease severity and
      prognosis remained unchanged. Regarding treatment in recent years, steroid pulse
      therapy became more available but the administration of warfarin and anti
      platelet drugs significantly decreased. CONCLUSION: We concluded that the rate of
      total primary MPGN and that of pediatric patients with primary MPGN decreased.

PMID- 22971964
TI  - Annual incidence of persistent proteinuria in the general population from Ibaraki
      annual urinalysis study.
AB  - BACKGROUND: For a definitive diagnosis of chronic kidney disease, at least 2
      consecutive positive results of proteinuria with an interval of >3 months are
      required. However, most previous reports were based on single-screening data.
      PATIENTS AND METHODS: The subjects in this study were participants in an annual
      health examination held in Ibaraki, Japan, between 1993 and 2003. The follow-up
      duration with serial urinalysis for 3 years of patients who were negative for
      proteinuria in the initial year was 330,614 person-years in males and 687,381
      person-years in females among 81,854 male and 155,256 female subjects. We
      evaluated the incidence and risk factor for the incidence of proteinuria and
      persistent proteinuria. RESULT: The annual incidence of proteinuria and
      persistent proteinuria was 1.31 and 0.33 % in males and 0.68 and 0.14 % in
      females. Among the subjects without hypertension and diabetes, the annual
      incidence was 0.81 and 0.16 % in males and 0.37 and 0.06 % in females,
      respectively. Risk analysis indicated that hypertension in males [hazard ratio
      (HR) 2.052] and females (2.477), diabetes in males (3.532) and females (3.534)
      and reduced renal function in males (3.097) and females (2.827) were significant
      positive risks for development of persistent proteinuria. CONCLUSION: By annual
      urinalysis screening of the general population, 1 out of 303 male subjects and 1
      out of 725 female subjects developed persistent proteinuria every year. Subjects
      with diabetes, hypertension and reduced renal function had a 2 or 3 times higher
      risk for the incidence of persistent proteinuria in both males and females.

PMID- 22971965
TI  - Autophagy: a novel therapeutic target for kidney diseases.
AB  - Autophagy meaning 'self-eating' in Greek, is a large-scale mechanism of
      intracellular degradation that seeks to maintain homeostasis in cells of all
      eukaryotes, from yeast to humans. Over the past several decades, autophagy
      research has actively proceeded both at home and abroad. As a result, studies
      have reported the physiological role of autophagy in different organs of mammals
      and of the role that impairment of its activation plays in the development of age
      related diseases, abnormal glucose-lipid metabolism, and neurodegenerative
      disorders. Currently, new therapies targeting the regulation of activation of
      autophagy are anticipated, and research is continuing. In recent years, the role
      of autophagy in the kidneys has gradually been elucidated, and reports are
      indicating an association between autophagy and the development of various kidney
      diseases. This paper reviews the molecular mechanisms regulating autophagy and
      discusses new findings from autophagy research on the kidney and issues that have
      yet to be resolved.

PMID- 22971967
TI  - [Colonoscopy: propofol well suited for sedation].

PMID- 22971966
TI  - Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces
      post-ischemic brain injury in mice with an extended therapeutic window.
AB  - Nuclear factor-kappaB (NF-kappaB) p50/RelA is a key molecule with a dual effect
      in the progression of ischemic stroke. In harmful ischemia, but not in
      preconditioning insult, neurotoxic activation of p50/RelA is characterized by
      RelA-specific acetylation at Lys310 (K310) and deacetylation at other Lys
      residues. The derangement of RelA acetylation is associated with activation of
      Bim promoter. OBJECTIVE: With the aim of producing neuroprotection by correcting
      altered acetylation of RelA in brain ischemia, we combined the pharmacological
      inhibition of histone deacetylase (HDAC) 1-3, the enzymes known to reduce global
      RelA acetylation, and the activation of sirtuin 1, endowed with a specific
      deacetylase activity on the K310 residue of RelA. To afford this aim, we tested
      the clinically used HDAC 1-3 inhibitor entinostat (MS-275) and the sirtuin 1
      activator resveratrol. METHODS: We used the mouse model of transient middle
      cerebral artery occlusion (MCAO) and primary cortical neurons exposed to oxygen
      glucose deprivation (OGD). RESULTS: The combined use of MS-275 and resveratrol,
      by restoring normal RelA acetylation, elicited a synergistic neuroprotection in
      neurons exposed to OGD. This effect correlated with MS-275 capability to increase
      total RelA acetylation and resveratrol capability to reduce RelA K310 acetylation
      through the activation of an AMP-activated protein kinase-sirtuin 1 pathway. The
      synergistic treatment reproduced the acetylation state of RelA peculiar of
      preconditioning ischemia. Neurons exposed to the combined drugs totally recovered
      the optimal histone H3 acetylation. Neuroprotection was reproduced in mice
      subjected to MCAO and treated with MS-275 (20MUg/kg and 200MUg/kg) or resveratrol
      (6800MUg/kg) individually. However, the administration of lowest doses of MS-275
      (2MUg/kg) and resveratrol (68MUg/kg) synergistically reduced infarct volume and
      neurological deficits. Importantly, the treatment was effective even when
      administered 7h after the stroke onset. Chromatin immunoprecipitation analysis of
      cortices harvested from treated mice showed that the RelA binding and histone
      acetylation increased at the Bcl-xL promoter and decreased at the Bim promoter.
      CONCLUSION: Our study reveals that epigenetic therapy shaping acetylation of both
      RelA and histones may be a promising strategy to limit post-ischemic injury with
      an extended therapeutic window.

PMID- 22971968
TI  - [Colonoscopy: is nitrous oxide helpful for sedation?].

PMID- 22971969
TI  - [More accurate determination of glomerular filtration rate by combined equation?-
      additional consideration of albuminuria is more important than cystatin C].

PMID- 22971970
TI  - [Inhouse coordination to promote organ donation: a pilot project in three full
      service hospitals].
AB  - BACKGROUND: There is still a lack of organ donors in Germany to provide organs
      for everyone on the waiting list. Against this background, the project "inhouse
      coordination" was initiated in 112 German hospitals in order to promote organ
      donation. We report the first results and experiences with this project at three
      full-service university hospitals. METHODS: From April 2010 to March 2011 data on
      all deceased patients with primary or secondary brain damage were collected
      retrospectively. The analysis of anonymised data was carried out by using the
      Software "Transplant-check" of the German Hospital Institute, as well as in-house
      databases. RESULTS: In comparison to the year before, no increase in numbers of
      organ donation was achieved during the study period. A total of 544 patients were
      deceased with a primary or secondary brain damage as main or secondary diagnosis.
      In 40.3 % medical contraindications prevented organ donation. In 34.5 % treatment
      limitation was introduced. Brain death was diagnosed in 59 of 544 patients (10.8
      %) and organ donation was possible in 5.5 %. CONCLUSION: In our analysis, a
      potential donor gap was noted which could not be clarified. Above all, it remains
      unclear in how many deceased patients with a fatal brain damage, the final
      diagnosis of brain death would have been possible. Even if these analyses did not
      lead to reliable results or conclusive evidence of organ donor potential,
      structural qualities were achieved in all hospitals. Ensuring the identification
      of potential organ donors and the accompanying support of the process should be
      of priority for future collaborative efforts of hospitals, transplant centers and
      the organ procurement organisation.

PMID- 22971971
TI  - [21-year-old woman with Reye's syndrome after influenza].
AB  - HISTORY AND ADMISSION FINDINGS: A 21-year old woman was referred to the hospital
      because of progressively deteriorating consciousness. Initially agitation and
      irritability, later confusion and delirium predominated. Previously influenza
      with high temperature, headache and vomiting had occurred and been treated with
      acetylsalicylic acid for some days. Non preliminary diseases were reported.
      CLINICAL INVESTIGATION: Besides of the deterioration in consciousness no clinical
      or neurological abnormalities were found. Electroencephalography demonstrated
      general abnormalities of medium range. Cranial magnetic resonance imaging and
      liquor investigations showed no pathological findings. In laboratory tests a
      marked increase of transaminases and ammonia were found. The toxicological
      screening was normal. TREATMENT AND COURSE: A hepatic encephalopathy due to acute
      hepatic failure was diagnosed and a detoxication of ammonemia with lactulose was
      started immediately. Transjugular liver biopsy showed a marked fattening of liver
      tissue without serological or histological findings for a reason. Because of
      progressive deterioration in consciousness mechanical ventilation became
      necessary. Despite of a rapid decline of ammonium serum levels further
      neurological deterioration occurred. Cranial computed tomography showed oedema of
      the cerebrum with beginning cerebral occlusion. Despite immediate therapy of
      cerebral oedema the patient died because of secondary cerebral oedema in hepatic
      encephalopathy. CONCLUSION: Reye's syndrome is an acute illness characterized by
      hepatic encephalopathy and fatty degeneration of the liver. It often occurs after
      viral infections. After a viral infection that was eventually treated with
      acetylsalicylic acid Reye's syndrome has to be discussed after exclusion of
      common causes of hepatic failure.

PMID- 22971972
TI  - [44-year-old patient with dyspnoea and hypertension. Stenosis of the aortic
      isthmus].

PMID- 22971973
TI  - [Oral treatment of type 2 diabetes mellitus].

PMID- 22971974
TI  - [Drug-induced impairment of renal function].
AB  - Acute kidney injury (AKI) of any origin is a common complication/disease in
      hospitalized patients, going along with significantly increased mortality and
      morbidity, as well as hospitalization duration and expenses. Drug-induced AKI is
      usually seen in patients with concurrent risk factors such as existing kidney
      disease, dehydration with or without hypotension, older age or diabetes mellitus.
      In cases with multiple risk factors or therapies the triggering drug is often
      impossible to define. Hemodynamic alterations, intrinsic tubulointerstitial
      damages and intrarenal (i. e. tubular) obstructions as a result of drug
      precipitations are the pathophysiological basis of this disease entity.
      Clinically the AKI is perceived as the most important problem, due to the
      development of hyperhydration (including pulmonary edema) and reduced/lacking
      clearance of toxic metabolites. The prognosis of drug-induced AKI is usually
      good, especially if the agents are stopped early in the process, but nevertheless
      some patients experience severe acute AKI requiring dialysis with/without
      subsequent restoration. Considering and recognizing potential risk factors may
      help to identify patients at risk and lead to introduction of prophylactic
      actions. Identification of risk factors and the introduction of prevention
      strategies should be an integral part of everybody's daily clinical work,
      especially in intensive care medicine due to the high susceptibility to AKI.

PMID- 22971975
TI  - [Multiple sclerosis and peripheral neuropathy].

PMID- 22971976
TI  - Plasmid DNA containing multiple CpG motifs triggers a strong immune response to
      hepatitis B surface antigen when combined with incomplete Freund's adjuvant but
      not aluminum hydroxide.
AB  - Adjuvants are important components of recombinant protein vaccines which are
      often poorly immunogenic. For decades, the search for new vaccine adjuvants has
      been predominantly empirical. In addition, combinations of more than one adjuvant
      plus antigen have been systematically studied. Plasmid DNA containing additional
      oligodeoxynucleotides with unmethylated CpG motifs (CpG ODN) entrapped in
      liposomes has been used as an adjuvant for DNA vaccines and has shown powerful
      immunostimulatory functions. In our study, the combination of plasmid DNA
      containing 16 additional CpG ODNs (pv-16CpG) and aluminum hydroxide (AL) or
      incomplete Freund's adjuvant (IFA) was used as an adjuvant for a hepatitis B
      surface antigen (HBsAg) vaccine to immunize C57BL/6J mice. ELISA and ELISPOT
      assays were used to analyze the immunological effects of the novel vaccine. A
      significant enhancement of the anti-HBs titer and seroconversion was observed
      when the CpG plasmid was combined with IFA, but not with AL. In addition, anti
      HBs antibody isotype analysis revealed that the combination of CpG plasmid and
      IFA induced a strong HBsAg-specific IgG2a response. Moreover, the ELISPOT assays
      suggested that pv-16CpG suspended in IFA evoked a strong T helper 1 (Th1) immune
      response and high IFN-gamma production. These results demonstrate that pv-16CpG
      suspended in IFA is able to induce cellular and humoral immune responses to
      HBsAg, and confirm its potential as an adjuvant for use in protein vaccines.

PMID- 22971977
TI  - ARF1 and ARF3 are required for the integrity of recycling endosomes and the
      recycling pathway.
AB  - Small GTPases ARF1 and ARF3 localize mainly to the Golgi apparatus, where they
      trigger formation of coated carrier vesicles. We previously showed that BIG2, a
      guanine nucleotide exchange factor specific for ARF1 and ARF3, localizes not only
      to the trans-Golgi network (TGN) but also to recycling endosomes, where it is
      involved in regulating the integrity of recycling endosomes. However, it is not
      yet clear whether ARF1 and ARF3 act downstream of BIG2 to ensure endosome
      integrity. In this study, we show that EGFP-tagged ARF1 and ARF3 localize to
      endosomal compartments containing endocytosed transferrin. We further demonstrate
      that simultaneous depletion of ARF1 and ARF3 induces tubulation of recycling
      endosomal compartments positive for transferrin receptor, Rab4, and Rab11, but
      does not significantly affect the integrity of the Golgi apparatus or early or
      late endosomes. Moreover, the simultaneous depletion of ARF1 and ARF3 suppresses
      recycling of transferrin but does not affect either its endocytosis or the
      retrograde transport of TGN38 from early/recycling endosomes to the TGN. In
      addition, depletion of ARF1 and ARF3 does not affect retrograde transport of CD4
      furin from late endosomes to the TGN, or of endocytosed EGF from late endosomes
      to lysosomes. These results indicate that ARF1 and ARF3 are redundantly required
      for the integrity of recycling endosomes, and that they regulate transferrin
      recycling from endosomes to the plasma membrane, but not retrograde transport
      from endosomal compartments to the TGN.

PMID- 22971978
TI  - Effects of sterilization and storage on the properties of ALP-grafted
      biomaterials for prosthetic and bone tissue engineering applications.
AB  - Grafting of the biomaterial surfaces with biomolecules is nowadays a challenging
      research field for prosthetic and bone tissue engineering applications. On the
      other hand, very few research works investigate the effect of the sterilization
      processes on the properties of functionalized biomaterials. In this study, the
      effects of different sterilization techniques (e.g. gamma and electron beam
      irradiation, ethylene oxide) on the enzymatic activity of bioactive glasses and
      Ti6Al4V grafted with alkaline phosphatase (ALP) have been analyzed. Sterility
      maintenance and in vitro bioactivity of the sterilized surfaces have also been
      investigated. Finally the effect of packaging and storage conditions has been
      considered.

PMID- 22971979
TI  - Experimental study of the effect of autologous platelet-rich plasma on the early
      phases of osteoinduction by allogenic demineralized bone matrix.
AB  - PURPOSE: To evaluate the effect of autologous platelet-rich plasma (PRP) on the
      early phases of osteoinduction by allogenic demineralized bone matrix (DBM) in
      rabbit intramuscular positions. MATERIALS AND METHODS: Allogenic DBM was produced
      from bones of 3 healthy rabbits. In each of 6 experimental animals, 0.3 mL
      autologous PRP was prepared and 2 muscle pouches were created, where 250 mg DBM +
      PRP (experimental sites) and 250 mg DBM without PRP (control sites) were randomly
      implanted. Animals were euthanized 3 weeks postoperatively. RESULTS: Histologic
      examination revealed uneventful healing in all cases, whereas remineralization of
      the periphery of the bone graft particles was a constant finding. In both control
      and experimental sites, fibroblasts and other mesenchymal cells (probably
      osteoprogenitor cells and preosteoblasts) were observed. The main histological
      difference was the recolonization of the empty lacunae of the bone graft
      particles by osteocytes at the control sites. The degradation of the graft at the
      control sites was statistically significantly quicker, although a statistically
      significant difference regarding the amount of the newly formed fibrous
      connective tissue was not observed. CONCLUSION: The present study demonstrated
      that in this experimental model, the addition of PRP to DBM had a negative effect
      on the early phases of osteoinduction at 3 weeks of observation.

PMID- 22971980
TI  - Prevention of lingual inclination of the transport segment in vertical
      distraction osteogenesis in the mandible.
AB  - Vertical distraction osteogenesis can extend not only to hard tissues but also to
      soft tissues. There is a tendency to cause progressive lingual inclination of the
      distracted segment. This study describes a method for preventing the lingual
      inclination of the transport segment in patients with vertical distraction
      osteogenesis in the anterior region of the mandible and reports the results of
      long-term follow-up. The subjects included 5 patients who had severely atrophic
      ridges in the anterior mandible. In all cases, a part of the mental protuberance
      was scraped out, and the distractor was placed suitably in a labioinclination
      beforehand. Therefore, the transport segments did not lean to the lingual side
      and had long-term stability.

PMID- 22971981
TI  - Evaluation of early bone response to fluoride-modified and anodically oxidized
      titanium implants through continuous removal torque analysis.
AB  - PURPOSE: To compare between a bioactive and a bioinert implant with different
      geometries by continuous measurement of the removal torque and calculation of the
      angular momentum of each surfaced implant. MATERIALS AND METHODS: Six New Zealand
      white rabbits were used in the study. Each rabbit received 2 implants. A
      bioactive fluoride-modified implant with a conical connection and microthread
      design was inserted into one tibia, and a bioinert anodically oxidized implant
      with an external connection design was inserted into the other. After 2 weeks of
      implant insertion, the removal torque values were continuously measured according
      to time. Using the time-torque curve resulting from the measurements, the maximum
      values were determined, and the angular momenta were calculated. RESULTS: The
      anodically oxidized implant had significantly higher peak removal torque and
      angular momentum values than the fluoride-modified implant (P < 0.05).
      CONCLUSIONS: The impact of the fluoride-modified bioactive implant on early bone
      response remains unclear. Considering the angular momentum of dental implants may
      assist in the elucidation of the effect of implant geometry on bone response.

PMID- 22971982
TI  - Hybrid implant education and the app.

PMID- 22971983
TI  - A new in vitro invasion model for oral cancer using an acellular allogenic dermal
      matrix (Alloderm): the relationship among in vitro invasion activity, in vivo
      invasion and metastasis.
AB  - The purpose of this study was to develop a new in vitro model of cancer invasion
      using a human  dermal equivalent, AlloDerm(r). A squamous cell carcinoma line
      (HSC-2, HSC-3 and OSC20) and a malignant  melanoma line (G361) were cultured on
      AlloDerm(r) and evaluated histologically to examine destruction of  the basement
      membrane and invasion into the dermis of AlloDerm(r). HSC-3 and G361 cells
      invaded through  the basement membrane of AlloDerm(r) at 21-28 days after
      seeding, while HSC-2 and OSC20 cells did not. Next,  these cells were
      transplanted into the tongues of nude mice, and the degree of local invasiveness
      was  examined histologically. HSC-3 and G361 cells invaded diffusely to the
      surrounding tongue tissue, although  HSC-2 and OSC20 showed only expansive
      growth. Further, these cells were transplanted subcutaneously in nude  mice to
      study metastatic activity. Regional and distant metastases were rarely observed
      after transplantation  of HSC-2 and OSC20 cells. On the other hand, HSC-3 and
      G361 cells frequently metastasized. These findings  show a close relationship
      among in vitro invasiveness on AlloDerm(r), in vivo invasiveness, and metastatic 
      activity. This experimental model using AlloDerm(r) is a potentially new in vitro
      model of cancer invasion.

PMID- 22971984
TI  - Prophylactic antibiotic administration for prevention of surgical site infection
      in  urological laparoscopic surgeries.
AB  - BACKGROUND: The purpose of this study is to investigate the occurrence of
      surgical site infection (SSI) in our cases after laparoscopic surgery with
      prophylactic antibiotics administration (PAA) of 1-2 days or 3 days duration.
      METHODS: Two hundred and nine patients were enrolled in this study. SSIs were
      categorized as urinary tract and/or wound infection. Laboratory data relating to
      infection such as serum white blood cell (WBC) and C-reactive protein (CRP) were
      investigated after surgeries and compared to the data before surgeries. Data were
      collected and analyzed retrospectively. RESULTS: There were 4 SSI patients in
      total. SSI was 4/125 (3.2 %) cases of PAA of 1-2 days (shorter) duration patients
      and there was 0/84 (0 %) of PAA of 3 days (longer) duration. Longer group showed
      the tendency of lower SSI ratio even though the difference did not reach
      statistically significant (p=0.0978) because of small number of SSI cases and
      ratios. Change of serum WBC at 4th day from pre-surgery was significantly
      suppressed in longer group than shorter group. CONCLUSIONS: Our data showed 3
      days of PAA might be better to be selected according to the cases especially such
      as, for instance, immune-compromised hosts. Future prospective study with more
      number of patients may be necessary for further evaluation.

PMID- 22971985
TI  - Effects of occupational therapy on hospitalized chronic schizophrenia patients
      with severe  negative symptoms.
AB  - The aim of this study was to determine whether occupational therapy (OT) can
      improve  the interpersonal relationships and negative symptoms of hospitalized
      chronic schizophrenia patients  with severe negative symptoms. Subjects were 38
      patients with chronic schizophrenia. They were randomly  divided into an OT group
      and a control group. Patients in the OT group participated in cooking  activities
      once a week for 15 weeks, while patients in the control group did not. During
      this  period, both groups had the usual treatment except for the cooking
      activities. In interviews,  the patient was asked to place a chair toward the
      interviewer (a therapist). The angle and distance  from the interviewer were
      taken as indicators of an ability to have interpersonal relationships.  Negative
      symptoms were evaluated with the Scale for the Assessment of Negative Symptoms
      (SANS).  Patients who received OT were able to sit at the smaller angle and
      shorter distance from the  interviewer than before OT (p=0.015 and p=0.013,
      respectively). The total SANS score was lower  after OT than before OT (p=0.033).
      In the control group, the distance from the interviewer also  decreased during
      the experimental period (p=0.040) but the seating angle and the SANS scores  did
      not change. The results suggest that OT can help to improve a relationship
      allowing the patient  to face the therapist and that it might improve negative
      symptoms of schizophrenia.

PMID- 22971986
TI  - The natural degeneration course in the T1rho values of normal knee cartilage.
AB  - The purpose of our study is to investigate whether there is an age-related change
      in T1 rho values and to evaluate the effects of weight bearing on age-related
      increase in T1  rho values of normal cartilage. Thirty-two asymptomatic patients
      were examined using a 3.0T  MRI to determine knee cartilage T1 rho values.
      Femorotibial and patella cartilage was defined  as weight-bearing cartilage (WB
      C) and non-weight-bearing cartilage (NWB-C), respectively.  The femoral cartilage
      was divided into weight-bearing (WB-P) and less-weight-bearing (LWB-P)  portions.
      Pearson's correlation coefficient and single regression analysis were used to
      assess  the relationship between cartilage T1 rho values and age. The slopes of
      the regression lines  of cartilage T1 rho values and age were compared between WB
      C and NWB-C and between WB-P and LWB-P.  Cartilage T1 rho values correlated
      positively with aging for all cartilage regions and all age  groups (p<0.001). In
      the medial femoral cartilage, the age-related increase in T1 rho values was 
      significantly greater for WB-P than for NWB-P (p<0.05). For several cartilage
      regions, this increase  was greater for WB-C than for LWB-C (p<0.05). The T1 rho
      value is very sensitive to age-related  cartilage degeneration and weight bearing
      related degeneration, and hence may be a very sensitive  and useful measure for
      the early diagnosis of osteoarthritis.

PMID- 22971987
TI  - Inflammablog: peer-to-peer online learning in immunology.
AB  - Is it possible for students in different courses, at different academic levels,
      and at different universities to learn immunology together using the Internet? We
      teach a colloquium on inflammation for undergraduates at the University of
      Arizona and a lecture course on human immunology for graduate students and
      clinical and basic science fellows at the University of Colorado Anschutz Medical
      Campus. Students in these programs, being scattered about large campuses, have
      little time for student-directed discussion and peer interactions, and they never
      have the opportunity to meet students in the course in the other state. Instead
      of requiring the usual essays and term papers, we set up a blog (an online
      discussion group) for the two courses, and required all students to post, and
      comment on other posts, within and between the courses. Student writing is
      normally directed at a single reader, the instructor, which seems like a waste of
      talent; we encouraged peer exchanges. Furthermore, we were interested in
      observing the interactions between the Colorado students, who were older and
      sometimes experienced professionals, and the younger Arizonans. We used a blog
      because it is administratively impossible to enroll the students in two
      universities in a single courseware (learning management system) site. Blogging
      has offered insights into students' comfort with this form of social medium, and
      into the potential for this approach in light of the rapid adoption of blended
      and massively open online courses.

PMID- 22971988
TI  - Novel autoantigens for diabetogenic CD4 T cells in autoimmune diabetes.
AB  - Autoreactive CD4 T cells play a central role in the development of type 1
      diabetes. The BDC panel of diabetogenic T cell clones was originally isolated
      from non-obese diabetic mice and has been used to study the role of autoreactive
      CD4 T cells and T cell autoantigens in the development of diabetes. Recent
      studies by our group have led to the identification of two new target antigens
      for clones of this panel. This review describes the proteomic strategy used for
      antigen identification, the antigens identified, and the potential contribution
      of post-translational modification to autoantigen generation. In addition, we
      compare peptide epitopes for the T cell clones and discuss their potential
      applications in investigating the role of T cell autoantigens in the pathogenesis
      and regulation of disease.

PMID- 22971989
TI  - Changes in the thyroid function of Graves' disease patients treated by subtotal
      thyroidectomy.
AB  - The extent of thyroidectomy in Graves' disease is still a matter of controversy. 
      Subtotal thyroidectomy has been used as the standard surgical procedure for
      Graves' disease in Japan, but high hyperthyroidism relapse rates have been
      reported.  We retrospectively studied serial changes in the thyroid function
      Graves' disease patients after they had been treated by subtotal thyroidectomy
      and assessed whether subtotal thyroidectomy should be recommended as the standard
      surgical procedure for the treatment of Graves' disease.  The subjects were 478
      Graves' disease patients who underwent subtotal thyroidectomy at our institution
      between 1994 and 1997 and were followed up on a regular basis, and their thyroid
      function 2-3 years after surgery (the early period) and 8-10 years after surgery
      (the late period) was evaluated and compared.  The evaluations in the late period
      showed that 57% of the euthyroid patients in the early period remained euthyroid,
      30% had developed a relapse of hyperthyroidism, and 13 % had become hypothyroid. 
      Approximately 80% of the patients who were overtly hyperthyroid or overtly
      hypothyroid in the early period remained so in the late period.  During the
      entire periods 47 patients had subclinical hyperthyroidism and were followed up
      without any postoperative medication.  Twenty (42.6%) of them developed overt
      hyperthyroidism, 11 (23.4%) experienced a spontaneous remission, and 16 (34%)
      continued to be subclinically hyperthyroid.  Because thyroid function after
      subtotal thyroidectomy is unstable and reduces quality of life, subtotal
      thyroidectomy is concluded not to be suitable as a standard surgical procedure
      for the treatment of Graves' disease.

PMID- 22971990
TI  - Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T
      cells.
AB  - Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key
      element low CD4 T-cell counts (below 300/mm3) without evidence of HIV infection
      or other known immunodeficiency. The etiology, pathogenesis, and management of
      ICL remain poorly understood and inadequately defined. The clinical presentation
      can range from serious opportunistic infections to incidentally diagnosed
      asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial
      infections and progressive multifocal leukoencephalopathy are the most
      significant presenting infections, although the spectrum of opportunistic
      diseases can be similar to that in patients with lymphopenia and HIV infection.
      Malignancy is common and related to opportunistic pathogens with an oncogenic
      potential. Autoimmune diseases are also seen in ICL with an increased incidence.
      The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may
      include decreased production, increased destruction, and tissue sequestration.
      New distinct genetic defects have been identified in certain patients with ICL,
      supporting the hypothesis of the lack of a common etiology in this syndrome. The
      management of ICL is focused on the treatment of opportunistic infections,
      appropriate prophylactic antibiotics, and close monitoring. In selected patients
      with life-threatening infections or profound immunodeficiency, strategies to
      increase T-cell counts or enhance immune function could be considered and have
      included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem
      cell transplantation. The prognosis is influenced by the accompanying
      opportunistic infections and may be affected by publication bias of severe cases
      with unfavorable outcomes. As newer laboratory investigation techniques are being
      developed and targeted experimental treatments become available, our
      comprehension and prognosis of this rare syndrome could be significantly
      improved.

PMID- 22971991
TI  - Plasma endothelin-1 level is a predictor of 10-year mortality in a general
      population: the Tanushimaru study.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor and an elevated
      plasma level is a prognostic marker in patients with cardiovascular diseases
      and/or malignancies. We hypothesized that an elevated plasma level might be a
      prognostic marker even in subjects without apparent cardiovascular disease or
      malignancy at baseline. METHODS AND RESULTS: We measured plasma ET-1 levels in
      1,440 healthy subjects over 40 years of age (580 men, 860 women) who were
      periodically followed for 10 years. The follow-up rate was 96.8%. Baseline plasma
      ET-1 levels were categorized into quartiles. Baseline plasma ET-1 levels were
      significantly associated with age, blood pressure, high-density lipoprotein
      cholesterol, renal function, uric acid and all-cause death, but not with
      cardiovascular or cancer death. Kaplan-Meier curves demonstrated that all-cause
      mortality was significantly higher in the highest quartile of ET-1 than in the
      lowest quartile. Cox proportional hazards regression analysis demonstrated that
      ET-1 was an independent predictor of all-cause death [hazard ratio: 1.11, 95%
      confidence interval (CI) 1.01-1.23 per 1 pg/ml difference]. The hazard ratio of
      all-cause death in the highest quartile of plasma ET-1 (>=5.9 pg/ml) vs. the
      lowest quartile after adjusting for confounding factors was 1.54 (95% CI 1.09
      2.20). CONCLUSIONS: The plasma ET-1 level may be a predictor of all-cause death
      in a healthy population.

PMID- 22971993
TI  - Intraductal injection of LPS as a mouse model of mastitis: signaling visualized
      via an NF-kappaB reporter transgenic.
AB  - Animal models of human disease are necessary in order to rigorously study stages
      of disease progression and associated mechanisms, and ultimately, as pre-clinical
      models to test interventions. In these methods, we describe a technique in which
      lipopolysaccharide (LPS) is injected into the lactating mouse mammary gland via
      the nipple, effectively modeling mastitis, or inflammation, of the gland. This
      simulated infection results in increased nuclear factor kappa B (NF-kappaB)
      signaling, as visualized through bioluminescent imaging of an NF-kappaB
      luciferase reporter mouse. Our ultimate goal in developing these methods was to
      study the inflammation associated with mastitis in the lactating gland, which
      often includes redness, swelling, and immune cell infiltration. Therefore, we
      were keenly aware that incision or any type of wounding of the skin, the nipple,
      or the gland in order to introduce the LPS could not be utilized in our methods
      since the approach would likely confound the read-out of inflammation. We also
      desired a straight-forward method that did not require specially made hand-drawn
      pipettes or the use of micromanipulators to hold these specialized tools in
      place. Thus, we determined to use a commercially available insulin syringe and to
      inject the agent into the mammary duct of an intact nipple. This method was
      successful and allowed us to study the inflammation associated with LPS injection
      without any additional effects overlaid by the process of injection. In addition,
      this method also utilized an NF-kappaB luciferase reporter transgenic mouse and
      bioluminescent imaging technology to visually and quantitatively show increased
      NF-kappaB signaling within the LPS-injected gland. These methods are of interest
      to researchers of many disciplines who wish to model disease within the lactating
      mammary gland, as ultimately, the technique described here could be utilized for
      injection of a number of substances, and is not limited to only LPS.

PMID- 22971992
TI  - EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb
      C nude mice through modulation of FKHRL1/FOXO3a and neuropilin.
AB  - Human pancreatic cancer is currently one of the fourth leading causes of cancer
      related mortality with a 5-year survival rate of less than 5 %. Since pancreatic
      carcinoma is largely refractory to conventional therapies, there is a strong
      medical need for the development of novel and innovative cancer preventive
      strategies. The forkhead transcription factors of the O class (FOXO) play a major
      role in cell proliferation, angiogenesis, metastasis, and tumorigenesis. The
      objectives of this study were to examine whether FKHRL1/FOXO3a modulates
      antitumor activity of (-)-epigallocatechin-3-gallate (EGCG), an active ingredient
      in green tea, in pancreatic cancer model in vivo. PANC-1 cells were
      orthotopically implanted into Balb c nude mice and gavaged with EGCG after tumor
      formation. Cell proliferation and apoptosis were measured by Ki67 and TUNEL
      staining, respectively. The expression of PI3K, AKT, ERK, and FOXO3a/FKHRL1 and
      its target genes were measured by the western blot analysis and/or q-RT-PCR. FOXO
      DNA binding was measured by gel shift assay. EGCG-treated mice showed significant
      inhibition in tumor growth which was associated with reduced phosphorylation of
      ERK, PI3K, AKT, and FKHRL1/FOXO3a, and modulation of FOXO target genes. EGCG
      induced apoptosis by upregulating Bim and activating caspase-3. EGCG modulated
      markers of cell cycle (p27/KIP1), angiogenesis (CD31, VEGF, IL-6, IL-8, SEMA3F,
      and HIF1alpha), and metastasis (MMP2 and MMP7). The inhibition of VEGF by EGCG
      was associated with suppression of neuropilin. EGCG inhibited epithelial
      mesenchymal transition by upregulating the expression of E-cadherin and
      inhibiting the expression of N-cadherin and Zeb1. These data suggest that EGCG
      inhibits pancreatic cancer orthotopic tumor growth, angiogenesis, and metastasis
      which are associated with inhibition of PI3K/AKT and ERK pathways and activation
      of FKHRL1/FOXO3a. As a conclusion, EGCG can be used for the prevention and/or
      treatment of pancreatic cancer.

PMID- 22971994
TI  - [Dose reduction in abdominal computed tomography].
AB  - CLINICAL/METHODICAL ISSUE: The broad availability and use of multidetector
      computed tomography (MDCT) in recent years has increased the radiation dose for
      patients. STANDARD RADIOLOGICAL METHODS: Multiphase MDCT protocols are used in
      abdominal imaging for various indications. METHODICAL INNOVATIONS: Dose reduction
      though novel technologies, such as dual energy CT or adapted contrast injection
      protocols (split bolus etc.) for reduction of scans. PRACTICAL RECOMMENDATIONS:
      An optimized dose reduction can be achieved by using strict protocols which are
      adapted to the clinical situation of the patient.

PMID- 22971996
TI  - A multinational cohort study of in-center daily hemodialysis and patient
      survival.
AB  - Increasing hemodialysis frequency from three to six times per week improves left
      ventricular mass and health-related quality of life; however, effects on survival
      remain uncertain. To study this, we identified 556 patients in the International
      Quotidian Dialysis Registry who received daily hemodialysis (more than five times
      per week) between 2001 and 2010. Using propensity score-based matching, we
      matched 318 of these patients to 575 contemporaneous patients receiving
      conventional (three times weekly) hemodialysis in the Dialysis Outcomes and
      Practice Patterns Study. All patients had session times of <5 h, and received
      dialysis in the clinic or hospital setting. Mortality rates between groups were
      compared using Cox proportional hazards regression. Mean dialysis frequency in
      the daily group was 5.8 sessions per week. Mean weekly treatment time was 15.7 h
      for daily and 11.9 h for conventional patients. During 1382 patient-years of
      follow-up, 170 patients died. Those receiving daily hemodialysis had a
      significantly higher mortality rate than those receiving conventional
      hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard
      ratio 1.6). Similar results were found in prespecified subgroup and sensitivity
      analyses. Unlike previous studies, we found that in-center daily hemodialysis was
      not associated with any mortality benefit. Thus, decisions to undertake daily
      hemodialysis should be based on quality-of-life improvements, rather than on
      claims of improved survival.

PMID- 22971997
TI  - A novel mutation, outside of the candidate region for diagnosis, in the inverted
      formin 2 gene can cause focal segmental glomerulosclerosis.
AB  - Focal and segmental glomerulosclerosis (FSGS) is a histological pattern that has
      several etiologies, including genetics. The autosomal dominant form of FSGS is a
      heterogenic disease caused by mutations within three known genes: alpha-actinin 4
      (ACTN4), canonical transient receptor potential 6 (TRPC6), and the inverted
      formin 2 (INF2) gene. More recently, INF2 mutations have also been attributed to
      Charcot-Marie-Tooth neuropathy associated with FSGS. Here we performed direct
      sequencing, histological characterization, and functional studies in a cohort of
      families with autosomal dominant FSGS. We detected a novel mutation in exon 6 of
      the INF2 gene outside of the exon 2-4 candidate region used for rapid diagnosis
      of autosomal dominant FSGS. This new mutation is predicted to alter a highly
      conserved amino-acid residue within the 17th alpha-helix of the diaphanous
      inhibitory domain of the protein. A long-term follow-up of this family indicated
      that all patients were diagnosed in adulthood, as opposed to early childhood, and
      progression to end-stage renal disease was at different times without clinical or
      electrodiagnostic evidence of neuropathy. Thus, this novel mutation in INF2
      linked to nonsyndromic FSGS indicates the necessity for full gene sequencing if
      no mutation is found in the current rapid-screen region of the gene.

PMID- 22971995
TI  - Tubular expression of heat-shock protein 27 inhibits fibrogenesis in obstructive
      nephropathy.
AB  - Morphological changes that occur during kidney injury involve actin skeleton
      remodeling. Here we tested whether heat-shock protein 27 (HSP27), a small stress
      response protein involved in cytoskeletal remodeling, protects the kidney from
      tubulointerstitial fibrosis in obstructive nephropathy. Tubular cell HSP27
      immunostaining was significantly increased in human kidneys with ureteropelvic
      junction obstruction, supporting the clinical relevance of our studies. To
      develop an animal model for mechanistic studies, we generated transgenic mice
      that specifically overexpress human HSP27 in renal tubules, under the kidney
      androgen-regulated protein promoter, and determined the effects of HSP27
      overexpression on epithelial-to-mesenchymal transition and tubulointerstitial
      fibrosis following unilateral ureteral obstruction. This was associated with
      decreased fibrogenesis as evidenced by significant declines in phosphorylated
      p38MAPK, collagen III, alpha-smooth muscle actin, 4-hydroxynonenal, and reduced
      trichrome staining following obstruction. Notably, E-cadherin and beta-catenin
      remained at the cell membrane of tubular cells in transgenic mice with an
      obstructed ureter. Monocyte/macrophage infiltration, however, was not
      significantly affected in these transgenic mice. Thus, tubular HSP27 inhibits
      fibrogenesis in obstructive nephropathy. Further studies are needed to determine
      pathways regulating the interactions between HSP27 and the E-cadherin-beta
      catenin complex.

PMID- 22971998
TI  - Associations of type 2 diabetes and diabetes treatment with breast cancer risk
      and mortality: a population-based cohort study among British women.
AB  - PURPOSE: There is great interest in whether type 2 diabetes and its treatments
      alter breast cancer risk and prognosis, but previous studies are inconclusive. We
      conducted a cohort study within the UK General Practice Research Database to
      investigate associations of type 2 diabetes and patterns of diabetes treatment
      with breast cancer risk and all-cause mortality. METHODS: We identified 52,657
      women with type 2 diabetes, diagnosed between 1987 and 2007, and 30,210 randomly
      selected women without diabetes. We performed a time-dependent analysis using Cox
      proportional hazards models. RESULTS: Diabetes was associated with a 29 %
      increased overall breast cancer risk (95 % CI: 1.16-1.44), but the association
      markedly attenuated when adjusted for age, period of cohort entry, region, and
      body mass index (BMI) (HR: 1.12; 95 % CI: 0.98-1.29). Women with breast cancer
      and pre-existing diabetes had a 49 % (95 % CI: 1.17-1.88) increased all-cause
      mortality risk compared with women with breast cancer but without diabetes, after
      controlling for age, period, region, BMI, smoking, alcohol, and deprivation.
      Compared with sulfonylurea, we found weak evidence that metformin monotherapy
      (HR: 1.04; 95 % CI: 0.79-1.37) and insulin (HR: 1.33; 95 % CI: 0.63-2.83)
      modified breast cancer risk among women with diabetes. CONCLUSIONS: We found weak
      evidence that diabetes is associated with a small increased risk of breast
      cancer. Among treated women, there is no evidence that anti-diabetes treatments
      modify the risk of developing breast cancer, with wide confidence intervals
      indicating imprecise effect estimates. Women with breast cancer and diabetes,
      however, had an increased all-cause mortality risk highlighting the potential
      importance of maintaining adequate glycemic control alongside anti-cancer
      treatments and subsequent follow-up.

PMID- 22971999
TI  - Understanding disparities in leukemia: a national study.
AB  - PURPOSE: Disparities in solid tumors have been well studied. However, disparities
      in hematologic malignancies have been relatively unexplored on population-based
      levels. The purpose of this study is to examine the relationship between
      race/ethnicity and acute leukemia mortality. METHODS: All patients with acute
      leukemia [acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia
      (AML)] were identified in the Surveillance Epidemiology and End Results database,
      1999-2008. Kaplan-Meier curves were generated to reflect survival probabilities
      by race/ethnicity. Multivariable Cox proportional hazard models estimated hazard
      of mortality by race with adjustment for individual (age, gender, year of
      diagnosis) and select genetic factors. RESULTS: A total of 39,002 patients with
      acute leukemia were included in the study. Overall, there was a mortality
      disparity in acute leukemia for blacks (HR 1.17, p < 0.0001) and Hispanics (HR
      1.13, p < 0.0001) compared with non-Hispanic whites. In stratified analysis,
      disparities in ALL were greater than AML; blacks (HR[ALL]1.45, p < 0.0001;
      HR[AML]1.12, p < 0.0011); Hispanics (HR[ALL]1.46, p < 0.0001; HR[AML]1.06, p <
      0.0001). Adjustment for individual patient and select genetic factors did not
      explain disparities. CONCLUSIONS: Blacks and Hispanics suffer decreased survival
      in acute leukemia as compared to others. Further investigation is needed to
      understand the drivers of poor cancer outcomes in these populations.

PMID- 22972001
TI  - Retraction note: Targeting EGFR in bladder cancer. World J Urol (2007) 25:573-9.

PMID- 22972000
TI  - Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from
      the NIH-AARP Diet and Health Study and systematic review.
AB  - BACKGROUND: Chronic inflammation has been proposed as a risk factor for ovarian
      cancer. Some data suggest that anti-inflammatory medications may be protective
      against ovarian cancer; however, results have been inconsistent. METHODS: We
      evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs
      prospectively in the NIH-AARP Diet and Health Study, using Cox proportional
      hazard models. We also examined the risk of common subtypes of epithelial ovarian
      cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with
      regular use of NSAIDs. In addition, we performed meta-analyses summarizing the
      risk of ovarian cancer with "regular use" of NSAIDs in previously published
      studies. RESULTS: We did not observe a significant association between regular
      use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95 %
      CI 0.87-1.29; non-aspirin NSAIDs: RR 0.93, 95 % CI 0.74-1.15); however, summary
      estimates from prospective cohort studies demonstrated that use of non-aspirin
      NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95 % CI 0.77-1.01).
      Although not significant, we found that mucinous tumors were inversely associated
      with non-aspirin NSAID use (RR 0.69, 95 % CI 0.23-2.10) in the AARP cohort, which
      was supported by the meta-analysis (RR 0.69, CI 0.50-0.94.) CONCLUSION: Although
      results from the NIH-AARP cohort study were not statistically significant, our
      meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian
      cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID
      use and accounting for ovarian cancer heterogeneity are necessary to further
      elucidate the association between NSAID use and ovarian cancer risk.

PMID- 22972003
TI  - Helium ion beam milling to create a nano-structured domain wall magnetoresistance
      spin valve.
AB  - We have fabricated and measured single domain wall magnetoresistance devices with
      sub-20 nm gap widths using a novel combination of electron beam lithography and
      helium ion beam milling. The measurement wires and external profile of the spin
      valve are fabricated by electron beam lithography and lift-off. The critical
      bridge structure is created using helium ion beam milling, enabling the formation
      of a thinner gap (and so a narrower domain wall) than that which is possible with
      electron beam techniques alone. Four-point probe resistance measurements and
      scanning electron microscopy are used to characterize the milled structures and
      optimize the He ion dose. Successful operation of the device as a spin valve is
      demonstrated, with a 0.2% resistance change as the external magnetic field is
      cycled. The helium ion beam milling efficiency as extracted from electrical
      resistance measurements is 0.044 atoms/ion, about half the theoretical value. The
      gap in the device is limited to a maximum of 20 nm with this technique due to sub
      surface swelling caused by injected ions which can induce catastrophic failure in
      the device. The fine patterning capabilities of the helium ion microscope milling
      technique indicate that sub-5 nm constriction widths could be possible.

PMID- 22972002
TI  - Clinical significance of preoperative peripheral blood neutrophil count in
      patients with non-metastatic upper urinary tract carcinoma.
AB  - PURPOSE: Preoperative elevation of markers of systemic inflammation is associated
      with a poor outcome in several cancers. The purpose of this study was to evaluate
      the prognostic significance of preoperative systemic inflammatory markers in
      patients with non-metastatic upper urinary tract cancer (UUTC). METHODS: The
      records of 84 patients with non-metastatic UUTC who had undergone
      nephroureterectomy were reviewed, and the associations between preoperative
      clinical variables and recurrence-free survival (RFS) were analyzed by univariate
      and multivariate analyses. RESULTS: Clinical tumor stage, neutrophil count, and
      neutrophil-to-lymphocyte ratio were significantly associated with RFS in
      univariate analysis. Multivariate analysis showed that clinical T stage (hazard
      ratio [HR], 3.009; 95 % confidence interval [CI], 1.149-9.321; p = 0.024) and
      neutrophil count (HR, 3.521; 95 % CI, 1.423-9.108; p = 0.007) were independent
      predictors of RFS. The 3-year RFS in patients with a neutrophil count <4,000/MUL
      was significantly higher than that in patients with a neutrophil count >=
      4,000/MUL (82.9 vs. 51.0 %, p = 0.004). Based on clinical T stage (T2 or less vs.
      T3 or greater) and neutrophil count (<4,000 vs. >= 4,000/MUL), patients were
      stratified into 3 groups: low, intermediate, and high risk groups. RFS rates were
      significantly different between the 3 groups (p = 0.0005). CONCLUSIONS:
      Preoperative neutrophil count was an independent predictor of RFS in patients
      with non-metastatic UUTC. Stratification of patients based on neutrophil count
      and clinical T stage may be valuable for preoperative patient counseling and
      identifying patients with poor prognosis who may be candidates for neoadjuvant
      chemotherapy.

PMID- 22972004
TI  - Genomics-driven discovery of taiwachelin, a lipopeptide siderophore from
      Cupriavidus taiwanensis.
AB  - A genome mining study led to the identification of a previously unrecognised
      siderophore biosynthesis gene cluster in the nitrogen-fixing bacterium
      Cupriavidus taiwanensis LMG19424. Based upon predicted structural residues, a
      convenient strategy for an NMR-assisted isolation of the associated metabolite
      was designed. The structure of the purified siderophore, taiwachelin, was fully
      characterized by spectroscopic methods and chemical derivatisation.

PMID- 22972005
TI  - Artificial enzymes based on supramolecular scaffolds.
AB  - Enzymes are nanometer-sized molecules with three-dimensional structures created
      by the folding and self-assembly of polymeric chain-like components through
      supramolecular interactions. They are capable of performing catalytic functions
      usually accompanied by a variety of conformational states. The conformational
      diversities and complexities of natural enzymes exerted in catalysis seriously
      restrict the detailed understanding of enzymatic mechanisms in molecular terms. A
      supramolecular viewpoint is undoubtedly helpful in understanding the principle of
      enzyme catalysis. The emergence of supramolecular artificial enzymes therefore
      provides an alternative way to approach the structural complexity and thus to
      unravel the mystery of enzyme catalysis. This critical review covers the recent
      development of artificial enzymes designed based on supramolecular scaffolds
      ranging from the synthetic macrocycles to self-assembled nanometer-sized objects.
      Such findings are anticipated to facilitate the design of supramolecular
      artificial enzymes as well as their potential uses in important fields, such as
      manufacturing and food industries, environmental biosensors, pharmaceutics and so
      on.

PMID- 22972010
TI  - Is there a role for simultaneous hepatic and colorectal resections? A
      contemporary view from NSQIP.
AB  - INTRODUCTION: The optimal timing of primary and metastatic tumor management in
      patients with synchronous hepatic colorectal metastases remains controversial. We
      aimed to compare perioperative outcomes of simultaneous colorectal/liver
      resection (SCLR) with isolated resections utilizing a national clinical database.
      METHODS: NSQIP data from 2005 to 2009 were examined to construct risk-adjusted
      generalized linear models and to calculate group-specific predicted estimates.
      These were used to compare 30-day perioperative outcomes among patients
      undergoing SCLR with colorectal (CR) and liver resections (LR) only in patients
      with metastatic colorectal cancer. RESULTS: A total of 3,983 patients were
      identified, who underwent SCLR (192), LR (1,857), or CR (1,934). Rectal resection
      was performed in 45 (23.4 %) SCLR patients and 269 (13.9 %) CR patients (p <
      0.001). Major hepatectomy was performed in 69 (35.9 %) SCLR patients and 774
      (41.7 %) LR patients (p = 0.12). Median adjusted operation time (SCLR: 273 min,
      95 % CI: 253-295; CR: 172, CI: 168-177; LR: 222, CI: 217-228; p < 0.001) and
      median adjusted length of hospital stay (SCLR: 9.5 days, CI: 8.8-10.4; CR: 8.1,
      CI: 7.9-8.3; LR: 6.4, CI: 6.3-6.6; p < 0.001) were longer for SCLR compared to CR
      and LR. Adjusted predicted risks for at least one postoperative complication were
      higher in SCLR (36.3 %) than in CR (26.6 %) and LR (19.8 %) (p < 0.003), mostly
      due to infectious/cardiopulmonary issues. DISCUSSION: In SCLR patients, the risk
      of 30-day adverse outcomes is higher, and median operation time as well as length
      of hospital stay is longer compared to CR and LR patients. However, the expected
      combined morbidities of staged procedures though likely favor SCLR in carefully
      selected patients undergoing even complex hepatic and colorectal resections and
      should be considered.

PMID- 22972011
TI  - Overweight patients operated on for cancer of the esophagus survive longer than
      normal-weight patients.
AB  - BACKGROUND: Esophageal adenocarcinoma is often associated with obesity, and a 5
      Kg m(-2) increase in body mass index (BMI) has, in fact, been found to be
      strongly associated with the risk of this type of cancer (RR, 1.52; p < 0.0001).
      Esophagectomy with lymphoadenectomy is the mainstay of therapy for these
      patients. The aim of this study was to assess and compare the surgical and
      oncological outcomes as well as the survival rates of underweight, normal weight,
      overweight, and obese patients following esophagectomy for esophageal cancer.
      PATIENTS AND METHODS: Data relative to 1,127 patients with esophageal
      adenocarcinoma presenting at a specialized tertiary hospital (the Center of
      Esophageal Diseases for the Veneto Region) between 2000 and 2008 were
      prospectively collected. The 278 subjects whose BMI values before disease onset
      were available and underwent esophagectomy were enrolled in the study. Sixty-one
      of the 278 patients were classified as obese (BMI >30), 121 were classified as
      overweight (BMI, 25-29.9), 81 were classified as normal weight (BMI <24.9), and
      15 ones as underweight (BMI <20). The outcome and survival of the four groups
      were compared. Frequency and survival analyses were carried out. RESULTS: The
      rate of R0 esophagectomy and the incidence of toxicity during neoadjuvant
      chemotherapy were similar in the four groups. Respiratory complications after R0
      esophagectomy seemed to be more frequent in the underweight and normal-weight
      patients group (p < 0.01). Moreover, underweight patients had a significantly
      higher rate of septic, cardiovascular, and metabolic postoperative complications.
      The 121 overweight patients had a better overall survival rate compared to normal
      weight and obese patients (p = 0.05). This difference was not significant if
      patients were stratified in stages I or II or stages III or IV. CONCLUSION:
      Overweight patients seem to respond better to esophageal cancer and esophagectomy
      with respect to normal-weight ones. This data seem to suggest that in spite of
      several unfavorable features, a moderate increase of weight may be helpful to
      survive after esophagectomy for cancer.

PMID- 22972012
TI  - Recognizing risk: bowel resection in the chronic renal failure population.
AB  - BACKGROUND: There is a paucity of quality data on the effects of chronic kidney
      disease in abdominal surgery. The aim of this study was to define the risk and
      outcome predictors of bowel resection in stage 5 chronic kidney disease using a
      large national clinical database. METHODS: The American College of Surgeons
      National Surgical Quality Improvement Program database was queried from years
      2005-2010 for major bowel resection in dialysis-dependent patients. Patient
      demographics, preoperative risk factors, and intraoperative variables were
      evaluated. Primary endpoints were mortality and morbidity after 30 days.
      Predictors of outcome were assessed by multivariate regression. RESULTS: The
      study included 1,685 patients with chronic kidney disease undergoing bowel
      resection. Overall mortality and morbidity were 27.5 and 58.3 %, respectively.
      Acute presentation was the strongest predictor of mortality (OR 2.39, CI 1.54
      3.72, p < 0.001). Other predictors of mortality included hypoalbuminemia (OR
      2.12, CI 1.39-3.24, p < 0.001), pulmonary comorbidity (OR 2.25, CI 1.67-3.03, p <
      0.001), and cardiac comorbidity (OR 1.54, CI 1.16-2.05, p = 0.003). CONCLUSION:
      This study demonstrates that bowel resection in patients with chronic kidney
      disease confers a high mortality risk. Preoperative optimization of comorbid
      conditions may reduce mortality after bowel resection in dialysis-dependent
      patients. In addition, laparoscopy was associated with a reduction in
      postoperative morbidity suggesting that it should be used preferentially.

PMID- 22972013
TI  - A case of refractory cutaneous polyarteritis nodosa in a patient with hepatitis B
      carrier status successfully treated with tumor necrosis factor alpha blockade.
AB  - We describe a patient with refractory cutaneous polyarteritis nodosa (CPAN) with
      hepatitis B virus (HBV) carrier status who was successfully treated with tumor
      necrosis factor alpha (TNF-alpha) blockade, using etanercept, and we review 5
      similar cases. We administered etanercept because of the occurrence of repeated
      flares despite aggressive therapy. C-reactive protein normalization; prednisolone
      dose-sparing; and absence of any adverse events, including HBV reactivation with
      nucleotide analogue administration, or renal dysfunction, have been achieved for
      8 months. TNF-alpha blockade should be considered for intractable CPAN. 

PMID- 22972014
TI  - MR-defined fat infiltration of the lumbar paravertebral muscles differs between
      non-radiographic axial spondyloarthritis and established ankylosing spondylitis.
AB  - OBJECTIVE: The aim of our study was to compare the magnetic resonance imaging
      (MRI)-defined cross-sectional area and semi-quantitative grading of fatty
      degeneration of lumbar paravertebral muscles in patients with non-radiographic
      axial spondyloarthritis (nr-axSpA) and established ankylosing spondylitis (AS).
      METHODS: Cross-sectional area (CSA) of lumbar paravertebral muscles, including
      the right and left multifidus (MF), erector spina (ES), psoas (PS), vertebral
      body and muscle:vertebra ratio (MVr), was measured. Fat infiltration of the
      paravertebral muscles was graded semi-quantitatively. RESULTS: The CSA of the MF,
      ES and PS muscles and the MVr (at the L2, L3, L4 and L5 levels) were quite
      similar between patients with nr-axSpA (n = 14) and AS (n = 22). However,
      patients with AS had higher grades of fat infiltration than those with nr-axSpA
      (Right L4 grading of MF + ES muscles: 1.4 +/- 0.73 vs. 0.51 +/- 0.52,
      respectively, p = 0.001; left L4 grading: 1.36 +/- 0.65 vs. 0.38 +/- 0.50,
      respectively, p < 0.0001). This difference remained significant after adjusting
      for age and symptom duration. The inter-rater reliability was good (intraclass
      correlation coefficient 0.75 and 0.85). CONCLUSIONS: This is first study
      demonstrating that MRI-defined fatty degeneration differs between patients with
      nr-axSpA and established AS. Semi-quantitative grading is reliable, and fatty
      degeneration of paravertebral muscles seems to be related to chronicity and
      spinal functions in patients with nr-axSpA and AS.

PMID- 22972016
TI  - Dynamics of serum angiopoietin-2 levels correlate with efficacy of intravenous
      pulse cyclophosphamide therapy for interstitial lung disease associated with
      systemic sclerosis.
AB  - OBJECTIVE: Angiopoietin-2 (Ang2) regulates the transition between vascular
      quiescence and angiogenesis in a context-dependent manner. In systemic sclerosis
      (SSc), serum Ang2 levels correlate with its disease activity. Therefore, we
      investigated the clinical significance of monitoring serum Ang2 levels during
      intravenous pulse cyclophosphamide (IVCY) therapy in SSc patients with
      interstitial lung disease (ILD). METHODS: Serum Ang2 levels were determined by a
      specific enzyme-linked immunosorbent assay in seven SSc patients treated with
      IVCY and 20 healthy controls. In the patient group, serum samples were drawn the
      day before each IVCY therapy. RESULTS: Serum Ang2 levels tended to be higher in
      SSc patients before IVCY than in healthy controls and significantly correlated
      with KL-6, surfactant protein D, erythrocyte sedimentation rate, and C-reactive
      protein in SSc patients with ILD. In sera drawn before the last IVCY, Ang2 levels
      were significantly decreased compared with initial levels. Notably, Delta serum
      Ang2 levels between baseline and after the first IVCY significantly correlated
      with Delta ILD score between before and after the entire IVCY therapy (r = 0.90,
      p < 0.01). CONCLUSION: Monitoring Ang2 levels during IVCY treatment may be useful
      to evaluate and predict the efficacy of this treatment for SSc-ILD.

PMID- 22972017
TI  - New insights into plant isoprenoid metabolism.

PMID- 22972018
TI  - Emergency neurological life support: acute non-traumatic weakness.
AB  - Acute non-traumatic weakness may be life-threatening if it involves respiratory
      muscles or is associated with dysautonomia. Most patients presenting with an
      acute muscle weakness have a worsening neurologic disorder that requires a rapid,
      systematic approach, and detailed neurologic localization of the findings. In
      many patients, urgent laboratory tests are needed and may involve neuroimaging.
      Because acute weakness is a common presenting sign of neurological emergencies,
      it was chosen as an Emergency Neurological Life Support protocol. An inclusive
      list of causes of acute weakness is explored, both by presenting complaint and
      anatomical location, with an outline of the key features of the history,
      examination, investigations, and treatment for each diagnosis.

PMID- 22972020
TI  - Investigating a sexual network of black men who have sex with men: implications
      for transmission and prevention of HIV infection in the United States.
AB  - BACKGROUND: HIV infections increased 48% among young Black men who have sex with
      men (MSM) in the United States between 2006 and 2009. Incomplete understanding of
      this trend undermines prevention strategy development. We investigated a sexual
      network to characterize the risk environment in which young Black MSM acquire
      HIV. METHODS: Persons reported to the state after diagnosis of HIV or syphilis
      were included, along with sexual partners. We used network mapping alongside
      descriptive and bivariate statistics to characterize network connections.
      Generalized linear models assessed predictors of having untraceable sex partners.
      RESULTS: The network included 398 individuals and 419 sexual relationships. Three
      quarters were Black (n = 299); 92% were MSM. Median age at first network
      appearance was 26 years and decreased over time (P < 0.001). HIV prevalence was
      at least 29% (n = 117); serostatus was unknown for 47% of the network, either
      because they were untraceable (n = 150) or refused HIV testing (n = 39). One in 5
      network members diagnosed with HIV had a subsequent incident sexually transmitted
      infection. In multivariable models, one-time encounters increased the risk of
      having an untraceable partner (risk ratio = 4.51, 95% CI: 2.27 to 8.97), whereas
      being acutely HIV infected at diagnosis reduced it (risk ratio = 0.27, 95% CI:
      0.08 to 0.89). CONCLUSIONS: HIV prevalence in this sexual network of young Black
      MSM rivals that of sub-Saharan Africa, reflecting dramatically increased risk of
      acquiring HIV from the moment one entered the network. Prevention efforts for
      this population must consider the effect of sexual networks on HIV risk and find
      ways of leveraging network structure to reduce transmission.

PMID- 22972019
TI  - Emergency neurological life support: airway, ventilation, and sedation.
AB  - Airway management is central to the resuscitation of the neurologically ill.
      These patients often have evolving processes that threaten the airway and
      adequate ventilation. Therefore, airway, ventilation, and sedation were chosen as
      an Emergency Neurological Life Support (ENLS) protocol. Reviewed topics include
      airway management; the decision to intubate; when and how to intubate with
      attention to cardiovascular status; mechanical ventilation settings; and the use
      of sedation, including how to select sedative agents based on the patient's
      neurological status.

PMID- 22972022
TI  - Increased frequency of anxiety, depression, quality of life and sexual life in
      young hypogonadotropic hypogonadal males and impacts of testosterone replacement
      therapy on these conditions.
AB  - Hypogonadotropic hypogonadism is defined as the failure in production of gonadal
      hormones, thus resulting in lower amounts of testosterone.  Depression, anxiety
      and decreased quality of life are the most common psychopathological conditions
      in young hypogonadal men.  The aim of the present study was to assess the still
      debated relationship with testosterone levels and psychological symptoms in young
      male patients with congenital hypogonadotropic hypogonadism (CHH).  Thirty-nine
      young male patients with CHH and 40 age-matched healthy males were enrolled in
      the present study.  The impact of testosterone replacement treatment (TRT) on the
      patients' anxiety and depression levels, sexual function and quality of life were
      assessed before and after 6 months of treatment using valid and reliable scales,
      including the Short Form-36 (SF-36), Beck Depression Inventory (BDI), Beck
      Anxiety Inventory (BAI), and Arizona Sexual Experiences (ASEX).  Patients with
      CHH had significantly higher scores for BDI, BAI, and ASEX than the control
      subjects at baseline (p=0.011, p=0.036, p<0.001, respectively).  The ASEX and BDI
      scores significantly improved after the TRT (p<0.001 for both), while the
      improvement in the BAI score was not statistically significant (p=0.135).  When
      compared to the control group, treatment naive hypogonadal patients had more
      severe symptoms of sexual dysfunction, anxiety, depression, and worse quality of
      life.  After 6 months of TRT, we observed improvements in the above parameters,
      suggesting that low endogenous levels of testosterone might be related to the
      increased incidence of psychological symptoms.

PMID- 22972021
TI  - Serum (1->3)-beta-D-glucan levels in HIV-infected individuals are associated with
      immunosuppression, inflammation, and cardiopulmonary function.
AB  - BACKGROUND: Translocation of gastrointestinal bacteria in HIV-infected
      individuals is associated with systemic inflammation, HIV progression, mortality,
      and comorbidities. HIV-infected individuals are also susceptible to fungal
      infection and colonization, but whether fungal translocation occurs and
      influences HIV progression or comorbidities is unknown. METHODS: Serum (1->3)
      beta-D-glucan (BG) was measured by a Limulus Amebocyte Lysate assay (Fungitell)
      in 132 HIV-infected outpatients. Selected plasma cytokines and markers of
      peripheral T-cell activation were measured. Pulmonary function testing and
      Doppler echocardiography were performed. Relationship of high (>=40 pg/mL) and
      low (<40 pg/mL) levels of BG with HIV-associated variables, inflammation markers,
      and pulmonary function and pulmonary hypertension measures were determined.
      RESULTS: Forty-eight percent of patients had detectable BG, and 16.7% had high
      levels. Individuals with high BG were more likely to have CD4 counts less than
      200 cells/MUL (31.8% vs. 8.4%, P = 0.002), had higher log10 HIV viral levels
      (2.85 vs. 2.13 log copies/mL, P = 0.004), and were less likely to use
      antiretroviral therapy (68.2% vs. 90.0%, P = 0.006). Plasma IL-8 (P = 0.033), TNF
      alpha (P = 0.029), and CD8CD38 (P = 0.046) and CD8HLA-DR (P = 0.029) were also
      increased with high levels. Abnormalities in diffusing capacity (P = 0.041) and
      in pulmonary artery pressures (P = 0.006 for pulmonary artery systolic pressure
      and 0.013 for tricuspid regurgitant velocity) were more common in those with high
      BG. CONCLUSIONS: We found evidence of peripheral fungal cell wall polysaccharides
      in an HIV-infected cohort. We also demonstrated an association between high serum
      BG, HIV-associated immunosuppression, inflammation, and cardiopulmonary
      comorbidity. These results implicate a new class of pathogen in HIV-associated
      microbial translocation and suggest a role in HIV progression and comorbidities.

PMID- 22972023
TI  - Nanocomposites of high-density polyethylene with amorphous calcium phosphate: in
      vitro biomineralization and cytocompatibility of human mesenchymal stem cells.
AB  - Polyethylene is widely used as a component of implants in medicine. Composites
      made of high-density polyethylene (HDPE) containing different amounts of
      amorphous calcium phosphate nanoparticles were investigated concerning their in
      vitro biomedical performance. The nanoparticles were produced by flame spray
      synthesis and extruded with HDPE, the latter complying with Food and Drug
      Administration regulations. Mechanical properties such as Young's modulus and
      contact angle as well as in vitro biomineralization of the nanocomposites hot
      pressed into thin films were evaluated. The deposition of a hydroxyapatite layer
      occurred upon immersion in simulated body fluid. Additionally, a cell culture
      study with human mesenchymal stem cells for six weeks allowed a primary
      assessment of the cytocompatibility. Viability assays (alamarBlue and lactate
      dehydrogenase detection) proved the absence of cytotoxic effects of the
      scaffolds. Microscopic images after hematoxylin and eosin staining confirmed
      typical growth and morphology. A preliminary experiment analyzed the alkaline
      phosphatase activity after two weeks. These findings motivate further
      investigations on bioactive HDPE in bone tissue engineering.

PMID- 22972024
TI  - A study of executive functions in delinquents with developmental disabilities
      within a Japanese reformatory.
AB  - Many attempts have been made to address the relation between antisocial behavior
      and executive  function deficits. The purpose of this paper is to evaluate
      executive functions in juvenile delinquents  with developmental disabilities by
      using the Behavioral Assessment of the Dysexecutive Syndrome (BADS),  and then
      cross referencing this to their performance on Wechsler IQ Test, Das Naglieri
      Cognitive  Assessment System (DN-CAS), and Rey's Auditory Verbal Learning Test
      (AVLT). The data was collected  from 164 participants with Mental Retardation
      (MR), Pervasive Developmental Disorder (PDD), and  Attention Deficit
      Hyperactivity Disorder (ADHD), and a factor analysis was applied to results of
      the BADS.  Two factors were extracted from the results; one factor was
      interpreted as low-degree of freedom executive  ability (LDF-EA) and the other
      factor as high-degree of freedom executive ability (HDF-EA). There was no 
      difference in IQ-matched groups with MR, ADHD and PDD, or in either factor in age
      and IQ-matched groups  with ADHD and PDD. While both factors had correlations
      with IQ and AVLT, where subjects were confined to  MR, the HDF-EA had no
      correlation. Neither factor showed correlation with the DN-CAS performance. 
      Moreover, scores of the LDF-EA increased associated with increases in IQ levels,
      however, scores of  the HDF-EA appeared broadly unrelated to IQ points. The
      results suggested that the HDF-EA could be  interpreted as a different level of
      executive functions compared to the LDF-EA. It is difficult to  evaluate
      executive abilities by using only IQ testing, and the BADS would be useful to
      assess the level  of high-degree of freedom executive functions.

PMID- 22972025
TI  - Physiological relevance of hydrolysis of atrial natriuretic peptide by endothelin
      converting enzyme-1.
AB  - Endothelin-converting enzyme-1 (ECE-1) is a membrane-bound metalloprotease that
      cleaves  biologically inactive big endothelin-1 (ET-1) into active ET-1. ET-1 is
      involved in the cardiovascular  homeostasis and the development of cardiovascular
      diseases including pulmonary arterial hypertension  and heart failure. Atrial
      natriuretic peptide (ANP) is an endogenous hormone that is released from the 
      heart in response to myocardial stretch and overload. ANP was shown to be
      hydrolyzed by neutral  endopeptidase 24.11 (NEP) which shares important
      structural features with ECE-1. Previous in vitro  studies using recombinant
      soluble ECE-1 suggested that ECE-1 cleaved several biologically active  peptides
      including ANP in addition to big ET-1. However, physiological relevance of ANP
      degrading  activity by ECE-1 has stayed unclear. Here, we aimed to investigate
      whether endogenous ECE-1 is  able to hydrolyze ANP using live-cell based assay
      and ECE-1-deficient mice. Chinese hamster  ovary (CHO) cells, which lack
      detectable levels of ECE activity, degraded ANP in the medium efficiently  when
      transfected with ECE-1 cDNA. ANP peptide contents in the E14-15 embryos were
      significantly higher  in ECE-1+/- mice compared with ECE-1+/+ mice. These
      observations strongly suggest that ECE-1 is involved  in the physiological
      degradation of ANP in vivo. Thus, pharmacological inhibition of ECE-1 may provide
      a novel strategy to treat various cardiovascular diseases by suppressing and
      potentiating the ET and  ANP pathway, respectively.

PMID- 22972026
TI  - Analysis of the 619 Branemark System TiUnite implants: a retrospective study.
AB  - The purpose of this retrospective study was to determine the outcome of Branemark
      System TiUnite(r) implants (Nobel Biocare/Sweden), and to identify the risk
      factors associated  with implant failure. A total of 151 patients (83 maxillae
      and 91 mandibles) received 619  implants from July 2003 until May 2010. The
      patients included 86 males and 65 females, with a  median age of 51.6 years and
      an age range of 16 to 90 years at the time of implant surgery.  Seventeen
      maxillae and 16 mandibles were completely edentulous, and 66 maxillae and 75
      mandibles  were partially edentulous. All the patients were followed until June
      2011. Among the 619 implants,  9 maxillary implants and 8 mandibular implants
      were unsuccessful. The overall survival rate was 96.82%.  A logistic regression
      analysis identified that a history of steroid treatment, application of a  dento
      maxillary prosthesis, a lack of mechanical coupling between the implants, and the
      length of  the implants (<=8.5mm) were significant predictors of implant failure.

PMID- 22972027
TI  - Nontraumatic true aneurysm of the superficial palmar arch: a case report.
AB  - A case of a 62 year-old woman with true aneurysm of the superficial palmar arch
      with no previous history of trauma is described. The aneurysm was resected
      without reconstruction based on intraoperative evidence of adequate finger
      perfusion after clumping the distal and proximal ends. Three years after the
      operation, there has been no recurrence of the aneurysm and the patient has
      neither complaints nor symptoms.

PMID- 22972028
TI  - Pingmu decoction enhances apoptosis of orbital adipocytes derived from patients
      with Graves' ophthalmophathy.
AB  - Graves' ophthalmopathy (GO), an autoimmune disease, has been demonstrated to
      result from an increased volume of orbital contents, including adipose,
      connective and extraocular muscle tissues. In our previous study, we showed that
      Pingmu decoction is capable of alleviating GO progression. In this study, to
      further investigate the underlying mechanism(s), we examined the effects of
      Pingmu decoction-containing serum on the proliferation and apoptosis of
      preadipocytes and adipocytes derived from the orbital adipose tissue of GO
      patients. Our data demonstrate for the first time that Pingmu decoction
      containing serum significantly reduces preadipocyte proliferation and increases
      adipocyte apoptosis as measured by MTT assay and Annexin V/FITC staining,
      respectively. Moreover, Pingmu decoction elevated the levels of cleaved caspase
      3, 8 and 9 and decreased the levels of cell cycle-related genes compared to those
      of the control. In addition, cell cycle arrest at the G0/G1 phase was observed
      following Pingmu decoction treatment. This study shows a mechanism by which
      Pingmu decoction serves as an effective GO medicine by downregulating
      preadipocyte proliferation and increasing adipocyte apoptosis.

PMID- 22972029
TI  - Tauroursodeoxycholate, a chemical chaperone, prevents palmitate-induced apoptosis
      in pancreatic beta-cells by reducing ER stress.
AB  - BACKGROUND: Free fatty acids (FFA) can have deleterious effects on beta-cells and
      promote type 2 diabetes, a process known as lipotoxicity. Recently, the induction
      of endoplasmic reticulum (ER) stress is one mechanism proposed to contribute to
      the detrimental effects of FFA on beta-cells. Tauroursodeoxycholic acid (TUDCA)
      has been reported to show cytoprotective effects by alleviating ER stress induced
      by some cytotoxic stimuli. The aim of this study was to investigate the effects
      of TUDCA on FFA (palmitate)-induced apoptosis and ER stress in rat islet beta
      cells. METHODS: The rat pancreatic beta-cell line INS-1 was cultured with
      palmitate (0.5 mM), or cultured togther with TUDCA (100 MUM), Annexin V
      fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess
      apoptosis in INS-1 cells. Cell viability was evaluated with MTT reduction
      conversion assay. The expressions of ER stress marker GRP78, ER stress-associated
      pro-apoptotic effectors CHOP and ATF4 were detected by Western blotting. RESULTS:
      TUDCA significantly reduced palmitate-induced cell apoptosis and growth
      inhibition in INS-1 cells. TUDCA also attenuated palmitate-induced expressions of
      GRP78, CHOP and ATF4 in INS-1 cells. CONCLUSIONS: Our results thus suggested that
      TUDCA could protect INS-1 cells from palmitate-induced injury, which might be due
      to the amelioration of ER stress and blocking the ATF4/CHOP signaling pathway.

PMID- 22972030
TI  - Angiopoietin-like protein 4 is differentially regulated by glucocorticoids and
      insulin in vitro and in vivo in healthy humans.
AB  - OBJECTIVE: Angiopoietin-like protein 4 (Angptl4) is a circulating inhibitor of
      plasma triglyceride clearance via inhibition of lipoprotein lipase. The aim of
      the present study was to examine the regulation of Angptl4 by glucocorticoids and
      insulin in vivo in humans, since these factors regulate Angptl4 expression in
      vitro. RESEARCH DESIGN AND METHODS: In a randomized, placebo-controlled, double
      blind, dose-response intervention study, 32 healthy males (age: 22 +/- 3 years;
      BMI 22.4 +/- 1.7 kg m-2) were allocated to prednisolone 30 mg once daily (n =
      12), prednisolone 7.5 mg once daily (n = 12), or placebo (n = 8) for 2 weeks.
      Angptl4 levels and lipid metabolism were measured before and at 2 weeks of
      treatment, in the fasted state and during a 2-step hyperinsulinemic clamp.
      Additionally, human hepatoma cells were treated with dexamethasone and/or
      insulin. RESULTS: Compared to placebo, prednisolone treatment tended to lower
      fasting Angptl4 levels (P = 0.073), raised fasting insulin levels (P = 0.0004)
      and decreased fasting nonesterified fatty acid concentrations (NEFA) (P = 0.017).
      Insulin infusion reduced Angptl4 levels by 6 % (plasma insulin ~200 pmol/l, P =
      0.006) and 22 % (plasma insulin ~600 pmol/l, P < 0.0001), which was attenuated by
      prednisolone treatment (P = 0.03). Prednisolone 7.5 mg and 30 mg dose-dependently
      decreased insulin-mediated suppression of lipolysis (by 11 +/- 5 % and 34 +/- 6 %
      respectively). Prednisolone 30 mg enhanced fasting triglyceride levels ( P =
      0.028). Plasma Angptl4 was not related to prednisolone-induced changes in lipid
      metabolism. In human hepatoma cells, dexamethasone increased Angptl4 mRNA
      expression and protein secretion, whereas insulin had the opposite effect.
      CONCLUSIONS: Insulin lowers plasma Angptl4 levels in humans by lowering NEFA and
      by inhibiting Angptl4 expression and release. Glucocorticoids counteract insulin
      mediated suppression of Angptl4.

PMID- 22972031
TI  - How do patients' preferences compare to the present spectrum of diabetes
      research?
AB  - OBJECTIVE: To compare patients' preferences in diabetes research to the current
      scientific research spectrum as presented during annual meetings of the European
      Association for the Study of Diabetes (EASD). METHODS: After dividing all
      scientific activities in diabetes research into 9 main fields, a questionnaire
      was published in a popular German weekly news magazine, inviting diabetic
      patients to express their research preferences. Thereafter, all abstracts
      accepted for publication at 2 recent EASD meetings were allocated to one of these
      research fields. RESULTS: In May and July 2011 the questionnaire was answered by
      652 patients with diabetes, 205 relatives and 61 other persons interested. The
      most important research fields were "development, pathophysiology and prevention
      of diabetes" (25.6%), "transplantation and cell therapy" (19.4%) and "blood
      glucose measurement and artificial pancreas" (16.5%). The most often covered
      topic of the 2,645 EASD abstracts was "development, pathophysiology and
      prevention" (46.3%), followed by "diabetes complications in man" (17.5%) and
      "special situations, training, psychology, treatment- and care structures"
      (10.5%). CONCLUSION: Views of diabetic patients and their relatives regarding
      their preferred research fields may differ when compared to current scientific
      activity in diabetology. Diabetic patients and their relatives should be involved
      in the weighting and selection of research topics more often.

PMID- 22972032
TI  - Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for
      drug therapies in rheumatoid arthritis: results of a randomized, two-center
      placebo-controlled study.
AB  - INTRODUCTION: We aimed to investigate the sensitivity and reliability of two
      dimensional ultrasonographic endpoints at the metacarpophalageal joints (MCPJs)
      and their potential to provide an early and objective indication of a therapeutic
      response to treatment intervention in rheumatoid arthritis (RA). METHODS: A
      randomized, double-blind, parallel-group, two-center, placebo-controlled trial
      investigated the effect on ultrasonographic measures of synovitis of repeat dose
      oral prednisone, 15 mg or 7.5 mg, each compared to placebo, in consecutive two
      week studies; there were 18 subjects in a 1:1 ratio and 27 subjects in a 2:1
      ratio, respectively. All subjects met the 1987 American College of Rheumatology
      criteria for the diagnosis of RA, were >=18 years-old with RA disease duration
      >=6 months, and had a Disease Activity Score 28 based on C-reactive protein
      (DAS28(CRP)) >=3.2. Subjects underwent high-frequency (gray-scale) and power
      Doppler ultrasonography at Days 1 (baseline), 2, 8 and 15 in the dorsal
      transverse and longitudinal planes of all 10 MCPJs to obtain summated scores of
      quantitative and semi-quantitative measures of synovial thickness as well as
      vascularity. The primary endpoint was the summated score of power Doppler area
      measured quantitatively in all 10 MCPJs in the transverse plane at Day 15.
      Clinical efficacy was assessed at the same time points by DAS28(CRP). RESULTS:
      All randomized subjects completed the trial. The comparison between daily 15 mg
      prednisone and placebo at Day 15 yielded a statistically significant treatment
      effect (effect size = 1.17, P = 0.013) in change from baseline in the primary
      endpoint, but borderline for prednisone 7.5 mg daily versus placebo (effect size
      = 0.61, P = 0.071). A significant treatment effect for DAS28(CRP) was only
      observed at Day 15 in the prednisone 15 mg group (effect size = 0.95, P = 0.032).
      However, significant treatment effects at all time points for a variety of
      ultrasound (US) endpoints were detected with both prednisone doses; the largest
      observed effect size = 2.33. Combining US endpoints with DAS28(CRP) improved the
      registration of significant treatment effects. The parallel scan inter-reader
      reliability of summated 10 MCPJ scores were good to excellent (ICC values >0.61)
      for the majority of US measures. CONCLUSIONS: Ultrasonography of MCPJs is an
      early, reliable indicator of therapeutic response in RA with potential to reduce
      patient numbers and length of trials designed to give preliminary indications of
      efficacy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00746512.

PMID- 22972033
TI  - Optical recording of suprathreshold neural activity with single-cell and single
      spike resolution.
AB  - Signaling of information in the vertebrate central nervous system is often
      carried by populations of neurons rather than individual neurons. Also
      propagation of suprathreshold spiking activity involves populations of neurons.
      Empirical studies addressing cortical function directly thus require recordings
      from populations of neurons with high resolution. Here we describe an optical
      method and a deconvolution algorithm to record neural activity from up to 100
      neurons with single-cell and single-spike resolution. This method relies on
      detection of the transient increases in intracellular somatic calcium
      concentration associated with suprathreshold electrical spikes (action
      potentials) in cortical neurons. High temporal resolution of the optical
      recordings is achieved by a fast random-access scanning technique using acousto
      optical deflectors (AODs). Two-photon excitation of the calcium-sensitive dye
      results in high spatial resolution in opaque brain tissue. Reconstruction of
      spikes from the fluorescence calcium recordings is achieved by a maximum
      likelihood method. Simultaneous electrophysiological and optical recordings
      indicate that our method reliably detects spikes (>97% spike detection
      efficiency), has a low rate of false positive spike detection (< 0.003
      spikes/sec), and a high temporal precision (about 3 msec). This optical method of
      spike detection can be used to record neural activity in vitro and in
      anesthetized animals in vivo.

PMID- 22972035
TI  - Profiles of ovarian steroids, luteinizing hormone and estrous signs from
      luteolysis to ovulation in lactating and non-lactating dairy cows.
AB  - The aims of the present study were to investigate the profiles of ovarian
      steroids and luteinizing hormone (LH) and the appearance of estrous signs in
      relation to luteolysis and ovulation in lactating and non-lactating cows and to
      examine the influence of lactation on those observations. Five lactating (daily
      milk yield of 28.4 +/- 3.2 kg; mean +/- SD) and five non-lactating cycling
      Holstein cows were examined. Their ovaries were monitored by ultrasonography
      daily during one estrous cycle. Blood samples were collected daily and then at 3
      h intervals after luteolysis until ovulation. Estrous signs in terms of behavior,
      the vulva and the vagina were checked at 8-h intervals after luteolysis until
      ovulation. Profiles of progesterone, estradiol-17beta and LH did not differ
      between the groups. There were no differences in the interval from luteolysis to
      ovulation (4.6 +/- 0.5 and 4.2 +/- 0.8 days) and the interval from the estradiol
      17beta peak to ovulation (34.2 +/- 4.5 and 30.6 +/- 3.9 h) between lactating and
      non-lactating cows. The interval from the peak of the LH surge to ovulation was
      27 h in all cows examined. Appearance of estrous signs did not differ between the
      groups. The vaginal estrous signs were observed conspicuously in all cows
      examined, but the behavioral signs were not observed in 20.0% of the cows. The
      duration of behavioral signs (41.3 +/- 23.6 h) was shorter (P<0.05) than that of
      the vagina (68.9 +/- 25.4 h). These results imply that lactation might not
      interfere with the hormonal profiles from luteolysis to ovulation.

PMID- 22972034
TI  - MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c
      MYC.
AB  - Multiple myeloma (MM) represents the malignant proliferation of terminally
      differentiated B cells, which, in many cases, is associated with the maintenance
      of high levels of the oncoprotein c-MYC. Overexpression of the histone
      methyltransferase MMSET (WHSC1/NSD2), due to t(4;14) chromosomal translocation,
      promotes the proliferation of MM cells along with global changes in chromatin;
      nevertheless, the precise mechanisms by which MMSET stimulates neoplasia remain
      incompletely understood. We found that MMSET enhances the proliferation of MM
      cells by stimulating the expression of c-MYC at the post-transcriptional level. A
      microRNA (miRNA) profiling experiment in t(4;14) MM cells identified miR-126* as
      an MMSET-regulated miRNA predicted to target c-MYC mRNA. We show that miR-126*
      specifically targets the 3'-untranslated region (3'-UTR) of c-MYC, inhibiting its
      translation and leading to decreased c-MYC protein levels. Moreover, the
      expression of this miRNA was sufficient to decrease the proliferation rate of
      t(4;14) MM cells. Chromatin immunoprecipitation analysis showed that MMSET binds
      to the miR-126* promoter along with the KAP1 corepressor and histone
      deacetylases, and is associated with heterochromatic modifications, characterized
      by increased trimethylation of H3K9 and decreased H3 acetylation, leading to miR
      126* repression. Collectively, this study shows a novel mechanism that leads to
      increased c-MYC levels and enhanced proliferation of t(4;14) MM, and potentially
      other cancers with high MMSET expression.

PMID- 22972036
TI  - Regulatory effect of hypoxia-inducible factor-1alpha on hCG-stimulated endothelin
      2 expression in granulosa cells from the PMSG-treated rat ovary.
AB  - Endothelin (ET)-2 plays a crucial role in ovarian ovulation in mammals. The
      present study was designed to test the hypothesis that hypoxia-inducible factor
      (HIF)-1alpha-mediated transcriptional activation contributes to the increased
      expression of ET-2 gene in response to hCG in rat ovarian granulosa cells (GCs)
      during gonadotropin-induced superovulation. By real-time RT-PCR analysis, ET-2
      mRNA expression was found to significantly increase in cultured ovarian GCs after
      treatment with hCG, or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal
      (MG-132), while this increased ET-2 mRNA expression could also be blocked by
      ferrous ammonium sulfate (FAS) under human chorionic gonadotropin (hCG)
      treatment. Further analysis also found that these changes of ET-2 mRNA were
      consistent with HIF-1alpha expression or HIF-1 activity, and HIF-1alpha inhibitor
      echinomycin inhibited ovulation in rats. Taken together, these results indicate
      that ET-2 is transcriptionally activated by hCG through HIF-1alpha-mediated
      mechanism in GCs. This HIF-1alpha-induced transcriptional activation may be one
      of the important mechanisms mediating the increase of ET-2 expression in GCs
      during the gonadotropin-induced mammalian ovulatory process in vivo.

PMID- 22972037
TI  - Structural and optical characterization of electrodeposited CdSe in mesoporous
      anatase TiO2 for regenerative quantum-dot-sensitized solar cells.
AB  - We investigated CdSe-sensitized TiO(2) solar cells by means of electrodeposition
      under galvanostatic control. The electrodeposition of CdSe within the mesoporous
      film of TiO(2) gives rise to a uniform, thickness controlled, conformal layer of
      nanostructured CdSe particles intimately wrapping the anatase TiO(2)
      nanoparticles. This technique has the advantage of providing not only a fast
      method for sensitization ( < 5 min) but also being easily scalable to the
      sensitization of large-area panels. XRD together with SAED analysis highlight
      that the deposit of CdSe is exclusively constituted of the hexagonal polymorph.
      In addition, hierarchical growth has also been shown, starting from the formation
      of a TiO(2)-CdSe core-shell structure followed by the growth of an assembly of
      CdSe nanoparticles resembling cauliflowers. This assembly exhibits at its core a
      mosaic texture with crystallites of about 3 nm in size, in contrast to a shell
      composed of well-crystallized single crystals between 5 and 10 nm in size.
      Preliminary results on the photovoltaic performance of such a nanostructured
      composite of TiO(2) and CdSe show 0.8% power conversion efficiency under A.M.1.5
      G conditions-100 mW cm(-2) in association with a new regenerative redox couple
      based on cobalt(+III/+II) polypyridil complex (V(oc ) = 485 mV, J(sc ) = 4.26 mA
      cm (-2), ff=0.37).

PMID- 22972038
TI  - Antenatal dietary advice and supplementation to increase energy and protein
      intake.
AB  - BACKGROUND: Gestational weight gain is positively associated with fetal growth,
      and observational studies of food supplementation in pregnancy have reported
      increases in gestational weight gain and fetal growth. OBJECTIVES: To assess the
      effects of advice during pregnancy to increase energy and protein intake, or of
      actual energy and protein supplementation, on energy and protein intakes, and the
      effect on maternal and infant health outcomes. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (22 July 2011) and
      contacted researchers in the field. We updated the search on 12 July 2012 and
      added the results to the awaiting classification section of the review. SELECTION
      CRITERIA: Randomised controlled trials of dietary advice to increase energy and
      protein intake, or of actual energy and protein supplementation, during
      pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trials for inclusion and assessed risk of bias. Two review authors
      independently extracted data and checked for accuracy. Extracted data were
      supplemented by additional information from the trialists we contacted. MAIN
      RESULTS: We examined 110 reports corresponding to 46 trials. Of these trials, 15
      were included, 30 were excluded, and one is ongoing. Overall, 15 trials involving
      7410 women were included.Nutritional advice (four trials, 790 women)Women given
      nutritional advice had a lower relative risk of having a preterm birth (two
      trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98 ), head
      circumference at birth was increased in one trial (389 women) (mean difference
      (MD) 0.99 cm, 95% CI 0.43 to 1.55) and protein intake increased (three trials,
      632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant
      differences were observed on any other outcomes.Balanced energy and protein
      supplementation (11 trials, 5385 women)Risk of stillbirth was significantly
      reduced for women given balanced energy and protein supplementation (RR 0.62, 95%
      CI 0.40 to 0.98, five trials, 3408 women), mean birthweight was significantly
      increased (random-effects MD +40.96  g, 95% CI 4.66 to 77.26 , Tau(2)= 1744, I(2)
      = 44%, 11 trials, 5385 women). There was also a significant reduction in the risk
      of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I(2) = 16%, seven
      trials, 4408 women). No significant effect was detected for preterm birth or
      neonatal death.High-protein supplementation (one trial, 1051 women)High-protein
      supplementation (one trial, 505 women), was associated with a significantly
      increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to
      2.41).Isocaloric protein supplementation (two trials, 184 women)Isocaloric
      protein supplementation (two trials,184 women) had no significant effect on
      birthweight and weekly gestational weight gain. AUTHORS' CONCLUSIONS: This review
      provides encouraging evidence that antenatal nutritional advice with the aim of
      increasing energy and protein intake in the general obstetric population appears
      to be effective in reducing the risk of preterm birth, increasing head
      circumference at birth and increasing protein intake, there was no evidence of
      benefit or adverse effect for any other outcome reported.Balanced energy and
      protein supplementation seems to improve fetal growth, and may reduce the risk of
      stillbirth and infants born small-for-gestational age. High-protein
      supplementation does not seem to be beneficial and may be harmful to the fetus.
      Balanced-protein supplementation alone had no significant effects on perinatal
      outcomes.The results of this review should be interpreted with caution, the risk
      of bias was either unclear or high for at least one category examined in several
      of the included trials and the quality of the evidence was low for several
      important outcomes. Also the anthropometric characteristics of the general
      obstetric population is changing, therefore, those developing interventions aimed
      at altering energy and protein intake should ensure that only those women likely
      to benefit are included. Large, well designed randomised trials are needed to
      assess the effects of increasing energy and protein intake during pregnancy in
      women whose intake is below recommended levels.

PMID- 22972039
TI  - Maternal dietary antigen avoidance during pregnancy or lactation, or both, for
      preventing or treating atopic disease in the child.
AB  - BACKGROUND: Some breastfed infants with atopic eczema benefit from elimination of
      cow milk, egg, or other antigens from their mother's diet. Maternal dietary
      antigens are also known to cross the placenta. OBJECTIVES: To assess the effects
      of prescribing an antigen avoidance diet during pregnancy or lactation, or both,
      on maternal and infant nutrition and on the prevention or treatment of atopic
      disease in the child. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (6 July 2012). SELECTION CRITERIA: All
      randomized or quasi-randomized comparisons of maternal dietary antigen avoidance
      prescribed to pregnant or lactating women. We excluded trials of multimodal
      interventions that included manipulation of the infant's diet other than breast
      milk or of non-dietary aspects of the infant's environment. DATA COLLECTION AND
      ANALYSIS: We extracted data from published reports, supplemented by additional
      information received from the trialists we contacted. MAIN RESULTS: The evidence
      from five trials, involving 952 participants, does not suggest a protective
      effect of maternal dietary antigen avoidance during pregnancy on the incidence of
      atopic eczema during the first 18 months of life. Data on allergic rhinitis or
      conjunctivitis, or both, and urticaria are limited to a single trial each and are
      insufficient to draw meaningful inferences. Longer-term atopic outcomes have not
      been reported. The restricted diet during pregnancy was associated with a
      slightly but statistically significantly lower mean gestational weight gain, a
      non-significantly higher risk of preterm birth, and a non-significant reduction
      in mean birthweight.The evidence from two trials, involving 523 participants, did
      not observe a significant protective effect of maternal antigen avoidance during
      lactation on the incidence of atopic eczema during the first 18 months or on
      positive skin-prick tests to cow milk, egg, or peanut antigen at one, two, or
      seven years.One crossover trial involving 17 lactating mothers of infants with
      established atopic eczema found that maternal dietary antigen avoidance was
      associated with a non-significant reduction in eczema severity. AUTHORS'
      CONCLUSIONS: Prescription of an antigen avoidance diet to a high-risk woman
      during pregnancy is unlikely to reduce substantially her child's risk of atopic
      diseases, and such a diet may adversely affect maternal or fetal nutrition, or
      both. Prescription of an antigen avoidance diet to a high-risk woman during
      lactation may reduce her child's risk of developing atopic eczema, but better
      trials are needed.Dietary antigen avoidance by lactating mothers of infants with
      atopic eczema may reduce the severity of the eczema, but larger trials are
      needed.

PMID- 22972040
TI  - Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.
AB  - BACKGROUND: Amnioinfusion aims to relieve umbilical cord compression during
      labour by infusing a liquid into the uterine cavity. OBJECTIVES: The objective of
      this review was to assess the effects of prophylactic amnioinfusion for women in
      labour with oligohydramnios, but not fetal heart deceleration, compared with
      therapeutic amnioinfusion only if fetal heart rate decelerations or thick
      meconium-staining of the liquor occur. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (28 February 2012). SELECTION
      CRITERIA: Randomised trials comparing prophylactic amnioinfusion in women in
      labour with oligohydramnios but not fetal heart rate deceleration in labour with
      therapeutic amnioinfusion. DATA COLLECTION AND ANALYSIS: The authors assessed
      trial quality and extracted data. MAIN RESULTS: One randomized trial of 116 women
      was included. No differences were found in the rate of caesarean section (risk
      ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in
      cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum
      endometritis. Prophylactic amnioinfusion was associated with increased
      intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05).
      AUTHORS' CONCLUSIONS: There appears to be no advantage of prophylactic
      amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart
      rate decelerations or thick meconium-staining of the liquor occur.

PMID- 22972041
TI  - Silver acetate for smoking cessation.
AB  - BACKGROUND: Silver acetate produces an unpleasant taste when combined with
      cigarettes, thereby producing an aversive stimulus. It has been marketed in
      various forms with the aim of extinguishing the urge to smoke, by pairing the
      urge with an unpleasant stimulus. OBJECTIVES: The aim of this review was to
      determine the effectiveness of silver acetate products (gum, lozenge, spray) in
      promoting smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco
      Addiction Group specialised trials register. Most recent search was in July 2012.
      SELECTION CRITERIA: We included randomised trials of silver acetate for smoking
      cessation with reports of smoking status at least six months after the beginning
      of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the
      type of subjects, the dose and form of silver acetate, the outcome measures,
      method of randomisation, and completeness of follow-up.The main outcome measure
      was biochemically validated abstinence from smoking after at least six months
      follow-up in patients smoking at baseline. Subjects lost to follow-up were
      counted as continuing smokers. Where appropriate, we performed meta-analysis
      using a fixed effects model. MAIN RESULTS: Two studies provided long-term follow
      up data on patients randomised to silver acetate or placebo. In one of these
      studies, there was a third arm, randomised to 2mg nicotine gum. The pooled risk
      ratio for quitting for silver acetate vs placebo was 1.04 (95% confidence
      interval 0.69 to 1.57). AUTHORS' CONCLUSIONS: Existing trials show little
      evidence for a specific effect of silver acetate in promoting smoking cessation.
      The confidence intervals for the ratio are quite wide. However, the upper limit
      of the confidence intervals for a positive effect equates to an absolute increase
      in the smoking cessation rate of about 4%. Any effect of this agent is therefore
      likely to be smaller than nicotine replacement therapy. The lack of effect of
      silver acetate may reflect poor compliance with a treatment whose rationale is to
      create an unpleasant stimulus.

PMID- 22972042
TI  - WITHDRAWN: Managements for people with disorders of sexual preference and for
      convicted sexual offenders.

PMID- 22972043
TI  - Planned hospital birth versus planned home birth.
AB  - BACKGROUND: Observational studies of increasingly better quality and in different
      settings suggest that planned home birth in many places can be as safe as planned
      hospital birth and with less intervention and fewer complications. This is an
      update of a Cochrane review first published in 1998. OBJECTIVES: To assess the
      effects of planned hospital birth compared with planned home birth in selected
      low-risk women, assisted by an experienced midwife with collaborative medical
      back up in case transfer should be necessary. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 March 2012) and
      contacted editors and authors involved with possible trials. SELECTION CRITERIA:
      Randomised controlled trials comparing planned hospital birth with planned home
      birth in low-risk women as described in the objectives. DATA COLLECTION AND
      ANALYSIS: The two review authors as independently as possible assessed trial
      quality and extracted data. We contacted study authors for additional
      information. MAIN RESULTS: Two trials met the inclusion criteria but only one
      trial involving 11 women provided some outcome data and was included. The
      evidence from this trial was of moderate quality and too small to allow
      conclusions to be drawn. AUTHORS' CONCLUSIONS: There is no strong evidence from
      randomised trials to favour either planned hospital birth or planned home birth
      for low-risk pregnant women. However, the trials show that women living in areas
      where they are not well informed about home birth may welcome ethically well
      designed trials that would ensure an informed choice. As the quality of evidence
      in favour of home birth from observational studies seems to be steadily
      increasing, it might be as important to prepare a regularly updated systematic
      review including observational studies as described in the Cochrane Handbook for
      Systematic Reviews of Interventions as to attempt to set up new randomised
      controlled trials.

PMID- 22972044
TI  - Piracetam for acute ischaemic stroke.
AB  - BACKGROUND: Piracetam has neuroprotective and antithrombotic effects that may
      help to reduce death and disability in people with acute stroke. This is an
      update of a Cochrane Review first published in 1999, and previously updated in
      2006 and 2009. OBJECTIVES: To assess the effects of piracetam in acute, presumed
      ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials
      Register (last searched 15 May 2011), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May
      2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May
      2011). We also contacted the manufacturer of piracetam to identify further
      published and unpublished studies. SELECTION CRITERIA: Randomised trials
      comparing piracetam with control, with at least mortality reported and entry to
      the trial within three days of stroke onset. DATA COLLECTION AND ANALYSIS: Two
      review authors extracted data and assessed trial quality and this was checked by
      the other two review authors. We contacted study authors for missing information.
      MAIN RESULTS: We included three trials involving 1002 patients, with one trial
      contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and
      both sexes were equally represented. Piracetam was associated with a
      statistically non-significant increase in death at one month (approximately 31%
      increase, 95% confidence interval 81% increase to 5% reduction). This trend was
      no longer apparent in the large trial after correction for imbalance in stroke
      severity. Limited data showed no difference between the treatment and control
      groups for functional outcome, dependence or proportion of patients dead or
      dependent. Adverse effects were not reported. AUTHORS' CONCLUSIONS: There is some
      suggestion (but no statistically significant result) of an unfavourable effect of
      piracetam on early death, but this may have been caused by baseline differences
      in stroke severity in the trials. There is not enough evidence to assess the
      effect of piracetam on dependence.

PMID- 22972045
TI  - Services for reducing duration of hospital care for acute stroke patients.
AB  - BACKGROUND: Stroke patients conventionally receive a substantial part of their
      rehabilitation in hospital. Services have now been developed which offer patients
      in hospital an early discharge with rehabilitation at home (early supported
      discharge (ESD)). OBJECTIVES: To establish the effects and costs of ESD services
      compared with conventional services. SEARCH METHODS: We searched the trials
      registers of the Cochrane Stroke Group (January 2012) and the Cochrane Effective
      Practice and Organisation of Care (EPOC) Group, MEDLINE (2008 to 7 February
      2012), EMBASE (2008 to 7 February 2012) and CINAHL (1982 to 7 February 2012). In
      an effort to identify further published, unpublished and ongoing trials we
      searched 17 trial registers (February 2012), performed citation tracking of
      included studies, checked reference lists of relevant articles and contacted
      trialists. SELECTION CRITERIA: Randomised controlled trials recruiting stroke
      patients in hospital to receive either conventional care or any service
      intervention which has provided rehabilitation and support in a community setting
      with an aim of reducing the duration of hospital care. DATA COLLECTION AND
      ANALYSIS: The primary patient outcome was the composite end-point of death or
      long-term dependency recorded at the end of scheduled follow-up. Two review
      authors scrutinised trials and categorised them on their eligibility. We then
      sought standardised individual patient data from the primary trialists. We
      analysed the results for all trials and for subgroups of patients and services,
      in particular whether the intervention was provided by a co-ordinated
      multidisciplinary team (co-ordinated ESD team) or not. MAIN RESULTS: Outcome data
      are currently available for 14 trials (1957 patients). Patients tended to be a
      selected elderly group with moderate disability. The ESD group showed significant
      reductions (P < 0.0001) in the length of hospital stay equivalent to
      approximately seven days. Overall, the odds ratios (OR) (95% confidence interval
      (CI)) for death, death or institutionalisation, death or dependency at the end of
      scheduled follow-up were OR 0.91 (95% CI 0.67 to 1.25, P = 0.58), OR 0.78 (95% CI
      0.61 to 1.00, P = 0.05) and OR 0.80 (95% CI 0.67 to 0.97, P = 0.02) respectively.
      The greatest benefits were seen in the trials evaluating a co-ordinated ESD team
      and in stroke patients with mild to moderate disability. Improvements were also
      seen in patients' extended activities of daily living scores (standardised mean
      difference 0.12, 95% CI 0.00 to 0.25, P = 0.05) and satisfaction with services
      (OR 1.60, 95% CI 1.08 to 2.38, P = 0.02) but no statistically significant
      differences were seen in carers' subjective health status, mood or satisfaction
      with services. The apparent benefits were no longer statistically significant at
      five-year follow-up. AUTHORS' CONCLUSIONS: Appropriately resourced ESD services
      provided for a selected group of stroke patients can reduce long-term dependency
      and admission to institutional care as well as reducing the length of hospital
      stay. We observed no adverse impact on the mood or subjective health status of
      patients or carers.

PMID- 22972046
TI  - Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative
      colitis.
AB  - BACKGROUND: Maintenance of remission is a major issue in inflammatory bowel
      disease. In ulcerative colitis, the evidence for the effectiveness of
      azathioprine and 6-mercaptopurine for the maintenance of remission is still
      controversial. OBJECTIVES: To assess the effectiveness and safety of azathioprine
      and 6-mercaptopurine for maintaining remission of ulcerative colitis. SEARCH
      METHODS: The MEDLINE, EMBASE and Cochrane Library databases were searched from
      inception to June 2012. A manual search was also performed using references from
      these articles as well as review articles, and proceedings from major
      gastrointestinal meetings. Authors of maintenance trials were asked about
      unpublished studies. SELECTION CRITERIA: Randomized controlled trials of at least
      12 months duration that compared azathioprine or 6-mercaptopurine with placebo or
      standard maintenance therapy (e.g. mesalazine) were included. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted data using standard forms.
      Disagreements were solved by consensus including a third author. Study quality
      was assessed using the Cochrane risk of bias tool. The primary outcome was
      failure to maintain clinical or endoscopic remission. Secondary outcomes included
      adverse events and withdrawal due to adverse events. Analyses were performed
      separately by type of control (placebo, or active comparator). Pooled risk ratios
      were calculated based on the fixed-effect model unless heterogeneity was shown.
      The GRADE approach was used to assess the overall quality of evidence for pooled
      outcomes. MAIN RESULTS: Six studies including 286 patients with ulcerative
      colitis were included in the review. The risk of bias was high in three of the
      studies due to lack of blinding. Azathioprine was shown to be significantly
      superior to placebo for maintenance of remission. Fourty-four per cent (51/115)
      of azathioprine patients failed to maintain remission compared to 65% (76/117) of
      placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE
      analysis rated the overall quality of the evidence for this outcome as low due to
      risk of bias and imprecision (sparse data). Two trials that compared 6
      mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant
      heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6-mercaptopurine
      patients failed to maintain remission compared to 100% (8/8) of mesalamine
      patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty-eight per
      cent (7/12) of azathioprine patients failed to maintain remission compared to 38%
      (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52, 95% CI 0.66 to
      3.50). One small study found that 6-mercaptopurine was superior to methotrexate
      for maintenance of remission. In the study, 50% (7/14) of 6-mercaptopurine
      patients and 92% (11/12) of methotrexate patients failed to maintain remission (1
      study, 26 patients; RR 0.55, 95% CI 0.31 to 0.95). All of the studies which used
      active comparators were open label. When placebo and active comparator studies
      were pooled to assess adverse events, there was no statistically significant
      difference between azathioprine and control in the incidence of adverse events.
      Nine per cent (11/127) of azathioprine patients experienced at least one adverse
      event compared to 2% (3/130) of placebo patients (5 studies, 257 patients; RR
      2.82, 95% CI 0.99 to 8.01). Patients receiving azathioprine were at significantly
      increased risk of withdrawing due to adverse events. Eight per cent (8/101) of
      azathioprine patients withdrew due to adverse events compared to 0% (0/98) of
      control patients (5 studies, 199 patients; RR 5.43, 95% CI 1.02 to 28.75).
      Adverse events related to study medication included acute pancreatitis (3 cases)
      and significant bone marrow suppression (5 cases). Deaths, opportunistic
      infection or neoplasia were not reported. AUTHORS' CONCLUSIONS: Azathioprine
      therapy appears to be more effective than placebo for maintenance of remission in
      ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as
      maintenance therapy for patients who have failed or cannot tolerate mesalazine or
      sulfasalazine and for patients who require repeated courses of steroids. More
      research is needed to evaluate superiority over standard maintenance therapy,
      especially in the light of a potential for adverse events from azathioprine. This
      review updates the existing review of azathioprine and 6-mercaptopurine for
      maintenance of remission in ulcerative colitis which was published in the
      Cochrane Library (Issue 1, 2007).

PMID- 22972047
TI  - Percutaneous transluminal balloon angioplasty and stenting for carotid artery
      stenosis.
AB  - BACKGROUND: Endovascular treatment by transluminal balloon angioplasty or stent
      insertion may be a useful alternative to carotid endarterectomy for the treatment
      of atherosclerotic carotid artery stenosis. This review updates a previous
      version first published in 1997 and subsequently updated in 2004 and 2007.
      OBJECTIVES: To assess the benefits and risks of endovascular treatment compared
      with carotid endarterectomy or medical therapy in patients with symptomatic or
      asymptomatic carotid stenosis. SEARCH METHODS: We searched the Cochrane Stroke
      Group Trials Register (last searched January 2012) and the following databases:
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2010, Issue 4), MEDLINE (1950 to January 2011), EMBASE (1980 to January
      2011) and Science Citation Index (1945 to January 2011). We also searched ongoing
      trials registers (January 2011) and reference lists and contacted researchers in
      the field. SELECTION CRITERIA: Randomised trials comparing endovascular treatment
      (including balloon angioplasty or stenting) with endarterectomy or medical
      therapy for symptomatic or asymptomatic atherosclerotic carotid stenosis. DATA
      COLLECTION AND ANALYSIS: One review author selected trials for inclusion,
      assessed trial quality and extracted data. A second review author independently
      validated trial selection and a third review author independently validated data
      extraction. We calculated treatment effects as odds ratios (OR) and 95%
      confidence intervals (CI), with endovascular treatment as the reference group. We
      quantified heterogeneity using the I(2) statistic. MAIN RESULTS: We included 16
      trials involving 7572 patients. In patients with symptomatic carotid stenosis at
      standard surgical risk, endovascular treatment was associated with a higher risk
      of the following outcome measures occurring between randomisation and 30 days
      after treatment than endarterectomy: death or any stroke (the primary safety
      outcome) (OR 1.72, 95% CI 1.29 to 2.31, P = 0.0003; I(2) = 27%), death or any
      stroke or myocardial infarction (OR 1.44, 95% CI 1.15 to 1.80, P = 0.002; I(2) =
      7%), and any stroke (OR 1.81, 95% CI 1.40 to 2.34, P < 0.00001;I(2) = 12%). The
      OR for the primary safety outcome was 1.16 (95% CI 0.80 to 1.67) in patients < 70
      years old and 2.20 (95% CI 1.47 to 3.29) in patients >= 70 years old (interaction
      P = 0.02).The rate of death or major or disabling stroke did not differ
      significantly between treatments (OR 1.28, 95% CI 0.93 to 1.77, P = 0.13; I(2) =
      0%). Endovascular treatment was associated with lower risks of myocardial
      infarction (OR 0.44, 95% CI 0.23 to 0.87, P = 0.02; I(2) = 0%), cranial nerve
      palsy (OR 0.08, 95% CI 0.05 to 0.14, P < 0.00001; I(2) = 0%) and access site
      haematomas (OR 0.37, 95% CI 0.18 to 0.77, P = 0.008; I(2) = 27%).The combination
      of death or any stroke up to 30 days after treatment or ipsilateral stroke during
      follow-up (the primary combined safety and efficacy outcome) favoured
      endarterectomy (OR 1.39, 95% CI 1.10 to 1.75, P = 0.005; I(2) = 0%), but the rate
      of ipsilateral stroke after the peri-procedural period did not differ between
      treatments (OR 0.93, 95% CI 0.60 to 1.45, P = 0.76; I(2) = 0%).Restenosis during
      follow-up was more common in patients receiving endovascular treatment than in
      patients assigned surgery (OR 2.41, 95% CI 1.28 to 4.53, P = 0.007; I(2) = 55%).
      In patients with asymptomatic carotid stenosis, treatment effects on the primary
      safety (OR 1.71, 95% CI 0.78 to 3.76, P = 0.18; I(2) = 0%) and combined safety
      and efficacy outcomes (OR 1.75, 95% CI 0.92 to 3.33, P = 0.09; I(2) = 0%) were
      similar to symptomatic patients, but differences between treatments were not
      statistically significant. Among patients not suitable for surgery, the rate of
      death or any stroke between randomisation and end of follow-up did not differ
      significantly between endovascular treatment and medical care (OR 0.22, 95% CI
      0.01 to 7.92, P = 0.41; I(2)= 79%). AUTHORS' CONCLUSIONS: Endovascular treatment
      is associated with an increased risk of peri-procedural stroke or death compared
      with endarterectomy. However, this excess risk appears to be limited to older
      patients. The longer term efficacy of endovascular treatment and the risk of
      restenosis are unclear and require further follow-up of existing trials. Further
      trials are needed to determine the optimal treatment for asymptomatic carotid
      stenosis.

PMID- 22972048
TI  - Alexander technique for chronic asthma.
AB  - BACKGROUND: 'The Alexander technique' is a taught form of physical therapy
      involving a series of movements designed to correct posture and bring the body
      into natural alignment with the object of helping it to function efficiently, and
      is reported to aid relaxation. Some practitioners claim benefits for those who
      desire greater ease and efficiency of breathing, including asthmatics.
      OBJECTIVES: The objective of this review was to evaluate the efficacy of the
      Alexander technique in people with chronic, stable asthma. SEARCH METHODS: We
      searched the Cochrane Airways Group Specialised Register, the Cochrane
      Complementary Medicine Field trials register and the bibliographies of relevant
      articles. The most recent search was run in June 2012. SELECTION CRITERIA:
      Randomised controlled trials of Alexander technique (AT) for the improvement of
      the symptoms of chronic, stable asthma, comparing the treatment with either
      another intervention or no intervention. DATA COLLECTION AND ANALYSIS: No trials
      were found that met the selection criteria. MAIN RESULTS: No meta-analysis could
      be performed. AUTHORS' CONCLUSIONS: Robust, well-designed randomised controlled
      trials are required in order to test claims by practitioners that AT can have a
      positive effect on the symptoms of chronic asthma and thereby help people with
      asthma to reduce medication.

PMID- 22972049
TI  - Antibiotics versus placebo for acute bacterial conjunctivitis.
AB  - BACKGROUND: Acute bacterial conjunctivitis is an infection of the conjunctiva.
      Both the palpebral and the bulbar ocular conjunctival surfaces are usually
      affected and typically become red and inflamed. Antibiotic therapy is widely used
      for the treatment of acute bacterial conjunctivitis. This Cochrane Review was
      first published in The Cochrane Library in 1999; updated in 2006 and again in
      2012. OBJECTIVES: To assess the benefits and harms of antibiotic therapy in the
      management of acute bacterial conjunctivitis. SEARCH METHODS: We searched CENTRAL
      (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane
      Library 2012, Issue 7), MEDLINE (January 1950 to July 2012), EMBASE (January 1980
      to July 2012), OpenGrey (System for Information on Grey Literature in Europe)
      (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled
      trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 18 July 2012. SELECTION CRITERIA: We included double-masked randomised
      controlled trials (RCTs) in which any form of antibiotic treatment had been
      compared with placebo/vehicle in the management of acute bacterial
      conjunctivitis. This included topical, systemic and combination (for example,
      antibiotics and steroids) antibiotic treatments. DATA COLLECTION AND ANALYSIS:
      Two authors (UN and SM) independently checked and reviewed the titles and
      abstracts of identified studies. We assessed the full text of all potentially
      relevant studies. We graded the included RCTs for methodological quality using
      Cochrane methodology. We performed data extraction in a standardised manner. We
      performed random-effects meta-analyses using RevMan. MAIN RESULTS: We identified
      11 eligible RCTs which randomised a total of 3673 participants. One further
      trial, which was published in abstract form in 1990 but has yet to be reported
      fully, is currently 'awaiting assessment'. Six of the 11 included studies have
      been included for the first time in this latest (2012) update. The trials were
      heterogeneous in terms of their inclusion and exclusion criteria, the nature of
      the intervention, and the outcome measures assessed. We judged two of the trials
      to be of high quality and graded the remainder as poor quality.Meta-analyses of
      data on clinical and microbiological remission rates revealed that topical
      antibiotics were of benefit in improving 'early' (days two to five) clinical
      (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.15 to 1.61) and
      microbiological (RR 1.55, 95% CI 1.37 to 1.76) remission rates. At the 'late'
      time point (days six to 10), antibiotics were found to still confer modest
      benefits in clinical remission (RR 1.21, 95% CI 1.10 to 1.33) and microbiological
      cure rates (RR 1.37, 95% CI 1.24 to 1.52). By days six to 10, 41% (95% CI 38 to
      43) of cases had resolved in those receiving placebo. We found no data on the
      cost-effectiveness of antibiotics. No serious outcomes were reported in either
      the active or placebo arms of these trials, suggesting that important sight
      threatening complications are an infrequent occurrence. AUTHORS' CONCLUSIONS:
      Although acute bacterial conjunctivitis is frequently self limiting, the findings
      from this updated systematic review suggest that the use of antibiotic eye drops
      is associated with modestly improved rates of clinical and microbiological
      remission in comparison to the use of placebo. Use of antibiotic eye drops should
      therefore be considered in order to speed the resolution of symptoms and
      infection.

PMID- 22972050
TI  - Voluntary counseling and testing (VCT) for changing HIV-related risk behavior in
      developing countries.
AB  - BACKGROUND: Voluntary counseling and testing (VCT) continues to play a critical
      role in HIV prevention, care and treatment. In recent years, different modalities
      of VCT have been implemented, including clinic-, mobile- and home-based testing
      and counseling. This review assesses the effects of all VCT types on HIV-related
      risk behaviors in low- and middle-income countries. OBJECTIVES: The primary
      objective of this review is to systematically review the literature examining the
      efficacy of VCT in changing HIV-related risk behaviors in developing countries
      across various populations. SEARCH METHODS: Five electronic databases - PubMed,
      Excerpta Medica Database (EMBASE), PsycINFO, Sociological Abstracts, and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL) - were searched
      using predetermined key words and phrases. Hand-searching was conducted in four
      key journals including AIDS, AIDS and Behavior, AIDS Education and Prevention,
      and AIDS Care; the tables of contents of these four journals during the included
      time period were individually screened for relevant articles. The reference lists
      of all articles included in the review were screened to identify any additional
      studies; this process was iterated until no additional articles were found.
      SELECTION CRITERIA: To be included in the review, eligible studies had to meet
      the following inclusion criteria: 1) Take place in a low- or middle-income
      country as defined by the World Bank, 2) Published in a peer-reviewed journal
      between January 1, 1990 and July 6, 2010, 3) Involve client-initiated VCT,
      including pre-test counseling, HIV-testing, and post-test counseling, and 4) Use
      a pre/post or multi-arm design that compares individuals before and after
      receiving VCT or individuals who received VCT to those who did not, and 5) Report
      results pertaining to behavioral, psychological, biological, or social HIV
      related outcomes. DATA COLLECTION AND ANALYSIS: All citations were initially
      screened and all relevant citations were independently screened by two reviewers
      to assess eligibility. For all included studies data were extracted by two team
      members working independently using a standardized form.  Differences were
      resolved through consensus or discussion with the study coordinator when
      necessary. Study rigor was assessed using an eight point quality score and
      through the Cochrane Collaboration's Risk of Bias Assessment Tool. Outcomes
      comparable across studies, including condom use and number of sex partners, were
      meta-analyzed using random effects models. With respect to both meta-analyses,
      data were included from multi-arm studies and from pre/post studies if adequate
      data were provided. Other outcomes, including HIV-incidence, STI
      incidence/prevalence, and positive and negative life events were synthesized
      qualitatively. For meta-analysis, all outcomes were converted to the standard
      metric of the odds ratio. If an outcome could not be converted to an odds ratio,
      the study was excluded from analysis. MAIN RESULTS:  An initial search yielded
      2808 citations. After excluding studies failing to meet the inclusion criteria,
      19 were deemed eligible for inclusion. Of these studies, two presented duplicate
      data and were removed. The remaining 17 studies were included in the qualitative
      synthesis and 8 studies were meta-analyzed.  Twelve studies offered  clinic-based
      VCT, 3 were employment-based, 1 involved mobile VCT, and 1 provided home-based
      VCT.  In meta-analysis, the odds of reporting increased number of sexual partners
      were reduced when comparing participants who received VCT to those who did not,
      unadjusted random effects pooled OR= 0.69 (95% CI: 0.53-0.90, p=0.007). When
      stratified by serostatus, these results only remained significant for those who
      tested HIV-positive. There was an insignificant increase in the odds of condom
      use/protected sex among participants who received VCT compared to those who did
      not, unadjusted random effects pooled OR=1.39 (95% CI: 0.97-1.99, p=0.076). When
      stratified by HIV status, this effect became significant among HIV-positive
      participants, random effects pooled OR= 3.24 (95% CI: 2.29-4.58, p<0.001).
      AUTHORS' CONCLUSIONS: These findings add to growing evidence that VCT can change
      HIV-related sexual risk behaviors thereby reducing HIV-related risk, and
      confirming its importance as an HIV prevention strategy. To maximize the
      effectiveness of VCT, more studies should be conducted to understand which
      modalities and counseling strategies produce significant reductions in risky
      behaviors and lead to the greatest uptake of VCT.

PMID- 22972051
TI  - Vitamin K antagonists versus antiplatelet therapy after transient ischaemic
      attack or minor ischaemic stroke of presumed arterial origin.
AB  - BACKGROUND: People who have had a transient ischaemic attack (TIA) or non
      disabling ischaemic stroke have an annual risk of major vascular events of
      between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary
      prevention trials after myocardial infarction indicate that treatment with
      vitamin K antagonists is associated with a risk reduction approximately twice
      that of treatment with antiplatelet therapy. OBJECTIVES: To compare the efficacy
      and safety of vitamin K antagonists and antiplatelet therapy in the secondary
      prevention of vascular events after cerebral ischaemia of presumed arterial
      origin. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register
      (last searched 15 September 2011), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September
      2011) and EMBASE (2008 to September 2011). In an effort to identify further
      relevant trials we searched ongoing trials registers and reference lists. We also
      contacted authors of published trials for further information and unpublished
      data. SELECTION CRITERIA: Randomised trials of oral anticoagulant therapy with
      vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus
      antiplatelet therapy for long-term secondary prevention after recent transient
      ischaemic attack or minor ischaemic stroke of presumed arterial origin. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials,
      assessed trial quality and extracted data. MAIN RESULTS: We included eight trials
      with a total of 5762 participants. The data showed that anticoagulants (in any
      intensity) are not more efficacious in the prevention of vascular events than
      antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80,
      95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR
      1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low
      intensity anticoagulation gives a higher bleeding risk than treatment with
      antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that
      medium and high intensity anticoagulation with vitamin K antagonists, with an INR
      of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding
      complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94;
      high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21). AUTHORS' CONCLUSIONS:
      For the secondary prevention of further vascular events after TIA or minor stroke
      of presumed arterial origin, there is sufficient evidence to conclude that
      vitamin K antagonists in any dose are not more efficacious than antiplatelet
      therapy and that medium and high intensity anticoagulation leads to a significant
      increase in major bleeding complications.

PMID- 22972052
TI  - Topical treatments for cutaneous warts.
AB  - BACKGROUND: Viral warts are a common skin condition, which can range in severity
      from a minor nuisance that resolve spontaneously to a troublesome, chronic
      condition. Many different topical treatments are available. OBJECTIVES: To
      evaluate the efficacy of local treatments for cutaneous non-genital warts in
      healthy, immunocompetent adults and children. SEARCH METHODS: We updated our
      searches of the following databases to May 2011: the Cochrane Skin Group
      Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005),
      EMBASE (from 2010), AMED (from 1985), LILACS (from 1982), and CINAHL (from 1981).
      We searched reference lists of articles and online trials registries for ongoing
      trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of topical
      treatments for cutaneous non-genital warts. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected trials and extracted data; a third author resolved
      any disagreements. MAIN RESULTS: We included 85 trials involving a total of 8815
      randomised participants (26 new studies were included in this update). There was
      a wide range of different treatments and a variety of trial designs. Many of the
      studies were judged to be at high risk of bias in one or more areas of trial
      design.Trials of salicylic acid (SA) versus placebo showed that the former
      significantly increased the chance of clearance of warts at all sites (RR (risk
      ratio) 1.56, 95% CI (confidence interval) 1.20 to 2.03). Subgroup analysis for
      different sites, hands (RR 2.67, 95% CI 1.43 to 5.01) and feet (RR 1.29, 95% CI
      1.07 to 1.55), suggested it might be more effective for hands than feet.A meta
      analysis of cryotherapy versus placebo for warts at all sites favoured neither
      intervention nor control (RR 1.45, 95% CI 0.65 to 3.23). Subgroup analysis for
      different sites, hands (RR 2.63, 95% CI 0.43 to 15.94) and feet (RR 0.90, 95% CI
      0.26 to 3.07), again suggested better outcomes for hands than feet. One trial
      showed cryotherapy to be better than both placebo and SA, but only for hand
      warts.There was no significant difference in cure rates between cryotherapy at 2
      , 3-, and 4-weekly intervals.Aggressive cryotherapy appeared more effective than
      gentle cryotherapy (RR 1.90, 95% CI 1.15 to 3.15), but with increased adverse
      effects.Meta-analysis did not demonstrate a significant difference in
      effectiveness between cryotherapy and SA at all sites (RR 1.23, 95% CI 0.88 to
      1.71) or in subgroup analyses for hands and feet.Two trials with 328 participants
      showed that SA and cryotherapy combined appeared more effective than SA alone (RR
      1.24, 95% CI 1.07 to 1.43).The benefit of intralesional bleomycin remains
      uncertain as the evidence was inconsistent. The most informative trial with 31
      participants showed no significant difference in cure rate between bleomycin and
      saline injections (RR 1.28, 95% CI 0.92 to 1.78).Dinitrochlorobenzene was more
      than twice as effective as placebo in 2 trials with 80 participants (RR 2.12, 95%
      CI 1.38 to 3.26).Two trials of clear duct tape with 193 participants demonstrated
      no advantage over placebo (RR 1.43, 95% CI 0.51 to 4.05).We could not combine
      data from trials of the following treatments: intralesional 5-fluorouracil,
      topical zinc, silver nitrate (which demonstrated possible beneficial effects),
      topical 5-fluorouracil, pulsed dye laser, photodynamic therapy, 80% phenol, 5%
      imiquimod cream, intralesional antigen, and topical alpha-lactalbumin-oleic acid
      (which showed no advantage over placebo).We did not identify any RCTs that
      evaluated surgery (curettage, excision), formaldehyde, podophyllotoxin,
      cantharidin, diphencyprone, or squaric acid dibutylester. AUTHORS' CONCLUSIONS:
      Data from two new trials comparing SA and cryotherapy have allowed a better
      appraisal of their effectiveness. The evidence remains more consistent for SA,
      but only shows a modest therapeutic effect. Overall, trials comparing cryotherapy
      with placebo showed no significant difference in effectiveness, but the same was
      also true for trials comparing cryotherapy with SA. Only one trial showed
      cryotherapy to be better than both SA and placebo, and this was only for hand
      warts. Adverse effects, such as pain, blistering, and scarring, were not
      consistently reported but are probably more common with cryotherapy.None of the
      other reviewed treatments appeared safer or more effective than SA and
      cryotherapy. Two trials of clear duct tape demonstrated no advantage over
      placebo. Dinitrochlorobenzene (and possibly other similar contact sensitisers)
      may be useful for the treatment of refractory warts.

PMID- 22972053
TI  - Intra-uterine insemination for unexplained subfertility.
AB  - BACKGROUND: Intra-uterine insemination (IUI) is a widely used fertility treatment
      for couples with unexplained subfertility. Although IUI is less invasive and less
      expensive than in vitro fertilisation (IVF), the safety of IUI in combination
      with ovarian hyperstimulation (OH) is debated. The main concern about IUI
      treatment with OH is the increase in multiple pregnancy rate. OBJECTIVES: To
      determine whether, for couples with unexplained subfertility, IUI improves the
      live birth rate compared with timed intercourse (TI), both with and without
      ovarian hyperstimulation (OH). SEARCH METHODS: We searched the Cochrane Menstrual
      Disorders and Subfertility Group Trials Register (searched July 2011), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2011, Issue 7), MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), PsycINFO
      (1806 to July 2011), SCIsearch and reference lists of articles. Authors of
      identified studies were contacted for missing or unpublished data. SELECTION
      CRITERIA: Truly randomised controlled trials (RCTs) with at least one of the
      following comparisons were included: IUI versus TI, both in a natural cycle; IUI
      versus TI, both in a stimulated cycle; IUI in a natural cycle versus IUI in a
      stimulated cycle; IUI with OH versus TI in a natural cycle; IUI in a natural
      cycle versus TI with OH. Only couples with unexplained subfertility were
      included. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction
      were performed independently by two review authors. Outcomes were extracted and
      the data were pooled. Subgroup and sensitivity analyses were done where possible.
      MAIN RESULTS: One trial compared IUI in a natural cycle with expectant management
      and showed no evidence of increased live births (334 women: odds ratio (OR) 1.60,
      95% confidence interval (CI) 0.92 to 2.8). In the six trials where IUI was
      compared with TI, both in stimulated cycles, there was evidence of an increased
      chance of pregnancy after IUI (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to
      2.50). A significant increase in live birth rate was found for women where IUI
      with OH was compared with IUI in a natural cycle (four RCTs, 396 women: OR 2.07,
      95% CI 1.22 to 3.50). However the trials provided insufficient data to
      investigate the impact of IUI with or without OH on several important outcomes
      including live births, multiple pregnancies, miscarriage and risk of ovarian
      hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI
      with OH compared with TI in a natural cycle (two RCTs, total 304 women: data not
      pooled). The final comparison of IUI in natural cycle to TI with OH showed a
      marginal, significant increase in live births for IUI (one RCT, 342 women: OR
      1.95, 95% CI 1.10 to 3.44). AUTHORS' CONCLUSIONS: There is evidence that IUI with
      OH increases the live birth rate compared to IUI alone. The likelihood of
      pregnancy was also increased for treatment with IUI compared to TI in stimulated
      cycles. One adequately powered multicentre trial showed no evidence of effect of
      IUI in natural cycles compared with expectant management. There is insufficient
      data on multiple pregnancies and other adverse events for treatment with OH.
      Therefore couples should be fully informed about the risks of IUI and OH as well
      as alternative treatment options.

PMID- 22972054
TI  - Interventions for recurrent corneal erosions.
AB  - BACKGROUND: Recurrent corneal erosion is a common cause of disabling ocular
      symptoms and predisposes the cornea to infection. It may follow corneal trauma.
      Measures to prevent the development of recurrent corneal erosion following
      corneal trauma have not been firmly established. Once recurrent corneal erosion
      develops simple medical therapy (standard treatment) may lead to resolution of
      the episode. However, some patients continue to suffer when such therapy fails
      and once resolved further episodes of recurrent erosion may occur. A number of
      treatment and prophylactic options are then available but there is no agreement
      as to the best option. OBJECTIVES: To assess the effectiveness and safety of
      prophylactic and treatment regimens for recurrent corneal erosion. SEARCH
      METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
      Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to
      June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean
      Literature on Health Sciences (LILACS) (January 1982 to June 2012), the
      metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use
      any date or language restrictions in the electronic searches for trials. We last
      searched the electronic databases on 13 June 2012. We also contacted researchers
      in the field. SELECTION CRITERIA: We included randomised and quasi-randomised
      trials that compared a prophylactic or treatment regimen with another
      prophylaxis/treatment or no prophylaxis/treatment for patients with recurrent
      corneal erosion. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data and assessed trial quality. We contacted study authors for
      additional information. MAIN RESULTS: Seven randomised and one quasi-randomised
      controlled trial were included in the review. The trials were heterogenous and of
      poor quality. Safety data presented were incomplete. For the treatment of
      recurrent corneal erosion, a single-centre trial in the UK with 30 participants
      showed that oral tetracycline 250 mg twice daily for 12 weeks or topical
      prednisolone 0.5% four times daily for one week, or both, in addition to standard
      treatment, accelerated healing rates and improved symptoms. A single-centre trial
      in Sweden with 56 participants showed that excimer laser ablation in addition to
      mechanical debridement may reduce the number of erosions and improve symptoms.
      Furthermore, in a single-centre trial in Germany with 100 participants,
      transepithelial technique for excimer laser ablation had the same efficacy as the
      traditional subepithelial excimer laser technique but caused less pain. In a
      small study of 24 participants in UK, therapeutic contact lens wear was inferior
      to lubricant drops and ointment in abolishing the symptoms of recurrent corneal
      erosion and had a high complication rate, although the contact lenses used were
      the older generation with low oxygen permeability. A recent study in Hong Kong
      with 48 participants found diamond burr polishing to reduce episodes of recurrent
      corneal erosion. For prophylaxis of further episodes of recurrent corneal
      erosion, there was no difference in the occurrence of objective signs of
      recurrent erosion between hypertonic saline ointment versus tetracycline ointment
      or lubricating ointment in a small Japanese study with 26 participants. Also, in
      a single-centre study in the UK with 117 participants, there was no difference in
      symptom improvement between hypertonic saline versus paraffin ointment when used
      for prophylaxis. In a UK study with 42 participants, lubricating ointment at
      night in addition to standard treatment to prevent recurrence following traumatic
      corneal abrasion (erosion) caused by fingernail injury led to increased symptoms
      of recurrent corneal erosion compared to standard therapy alone. AUTHORS'
      CONCLUSIONS: Well-designed, masked, randomised controlled trials using
      standardised methods are needed to establish the benefits of new and existing
      prophylactic and treatment regimes for recurrent corneal erosion. International
      consensus is also needed to progress research efforts towards evaluation of the
      major effective treatments for recurrent corneal erosions.

PMID- 22972055
TI  - Progestogens with or without oestrogen for irregular uterine bleeding associated
      with anovulation.
AB  - BACKGROUND: Irregular menstrual bleeding may arise due to exogenous sex steroids,
      lesions of the genital tract or be associated with anovulation. Irregular
      bleeding due to oligo/anovulation (previously called dysfunctional uterine
      bleeding or DUB) is more common at the extremes of reproductive life, and in
      women with ovulatory disorders such as polycystic ovary syndrome (PCOS). In
      anovulatory cycles there may be prolonged oestrogen stimulation of the
      endometrium without progesterone withdrawal and so cycles are irregular and
      bleeding may be heavy. This is the rationale for using cyclical progestogens
      during the second half of the menstrual cycle, in order to provoke a regular
      withdrawal bleed. Continuous progestogen is intended to induce endometrial
      atrophy and hence to prevent oestrogen-stimulated endometrial proliferation.
      Progestogens, and oestrogens and progestogens in combination, are widely used in
      the management of irregular menstrual bleeding, but the regime, dose and type of
      progestogen used vary widely, with little consensus about the optimum treatment
      approach. OBJECTIVES: To determine the effectiveness and acceptability of
      progestogens alone or in combination with oestrogens in the regulation of
      irregular menstrual bleeding associated with oligo/anovulation. SEARCH METHODS:
      We searched the following databases in February 2012: Cochrane Menstrual
      Disorders and Subfertility Group Trials Register, Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and reference lists of
      articles. SELECTION CRITERIA: All randomised controlled trials of progestogens
      (via any route) alone or in combination with oestrogens in the treatment of
      irregular menstrual bleeding associated with oligo/anovulation. DATA COLLECTION
      AND ANALYSIS: Study quality assessment and data extraction were carried out
      independently by two review authors. All authors were experts in the content of
      this review. MAIN RESULTS: No randomised trials were identified that compared
      progestogens with oestrogens and progestogens or with placebo in the management
      of irregular bleeding associated with oligo/anovulation. AUTHORS' CONCLUSIONS:
      There is a paucity of randomised studies relating to the use of progestogens and
      of oestrogens and progestogens in combination in the treatment of irregular
      menstrual bleeding associated with anovulation. There is no consensus about which
      regimens are most effective. Further research is needed to establish the role of
      these hormonal treatments in the management of this common gynaecological
      problem.

PMID- 22972056
TI  - Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane
      Review.
AB  - BACKGROUND: Epilepsy is an important neurological condition and drug resistance
      in epilepsy is particularly common in individuals with focal seizures. In this
      review, we summarise the current evidence regarding a new antiepileptic drug,
      levetiracetam, when used as add-on treatment for controlling drug-resistant focal
      epilepsy. This is an update to a Cochrane Review that was originally published in
      2001. OBJECTIVES: To evaluate the effectiveness of levetiracetam, added on to
      usual care, in treating drug-resistant focal epilepsy. SEARCH METHODS: We
      searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library
      Issue 7, 2012), and MEDLINE (1946 to August week 1, 2012). We also contacted the
      manufacturers of levetiracetam and researchers in the field to seek any ongoing
      or unpublished trials. SELECTION CRITERIA: Randomised, placebo-controlled trials
      of add-on levetiracetam treatment in people with drug-resistant focal epilepsy.
      DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials
      for inclusion, assessed trials for bias, extracted data, and evaluated the
      overall quality of evidence. Outcomes investigated included 50% or greater
      reduction in focal seizure frequency (response); less than 50% reduction in focal
      seizure frequency (non-response); treatment withdrawal; adverse effects
      (including a specific analysis of changes in behaviour); cognitive effects and
      quality of life (QoL). Risk ratios (RR) with 95% confidence intervals (CIs) were
      used as measures of effect (99% CIs for adverse effects). Primary analyses were
      Intention-to-Treat (ITT). Dose response and inter-trial heterogeneity were
      evaluated in regression models. MAIN RESULTS: Eleven trials (1861 participants)
      were included. They predominantly possessed low risks of bias. Participants were
      adults in nine trials (1565 participants) and children in the remaining two
      trials (296 participants). The dose of levetiracetam tested was 1000 to 4000
      mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24
      weeks. For the 50% or greater reduction in focal seizure frequency outcome, the
      RR was significantly in favour of levetiracetam at all doses. The naive
      estimates, ignoring dose, showed children (52% responded) as better responders
      than adults (39% responded) on levetiracetam. 25% of children and 16% of adults
      responded to placebo. The Number Needed to Treat for an additional beneficial
      outcome for children and adults was four (95% CI three to seven) and five (95% CI
      four to six), respectively. The significant levels of statistical heterogeneity
      between trials on adults precluded valid provision of an overall RR (ignoring
      dose). Results for the two trials that tested levetiracetam 2000 mg on adults
      were sufficiently similar to be combined to give an RR for 50% or greater
      reduction in focal seizure frequency of 4.91 (95% CI 2.75 to 8.77), with an RR of
      0.68 (95% CI 0.60 to 0.77) for non-response. At this dose, 37% and 8% of adults
      were responders in the levetiracetam and placebo groups, respectively. Regression
      analysis demonstrated that much of the heterogeneity between adult trials was
      likely to be explained by different doses of levetiracetam tested and different
      years of trial publication. There was no evidence of statistical heterogeneity
      between trials on children. For these trials, the RR for 50% or greater reduction
      in focal seizure frequency was 1.91 (95% CI 1.38 to 2.63), with an RR of 0.68
      (95% CI 0.56 to 0.81) for non-response. 27% of children responded. Participants
      were not significantly more likely to have levetiracetam withdrawn (RR 0.98; 95%
      CI 0.73 to 1.32 and RR 0.80; 95% CI 0.43 to 1.46 for adults and children,
      respectively). For adults, somnolence (RR 1.51; 99% CI 1.06 to 2.17) and
      infection (RR 1.76; 99% CI 1.03 to 3.02) were significantly associated with
      levetiracetam. Accidental injury was significantly associated with placebo (RR
      0.60; 99% CI 0.39 to 0.92). No individual adverse effect was significantly
      associated with levetiracetam in children. Changes in behaviour were negligible
      in adults (1% affected; RR 1.79; 99% CI 0.59 to 5.41) but significant in children
      (23% affected; RR 1.90; 99% CI 1.16 to 3.11). Cognitive effect and QoL outcomes
      suggested that levetiracetam had a positive effect on cognition and some aspects
      of QoL in adults. In children, levetiracetam did not appear to alter cognitive
      function but there was evidence of worsening in certain aspects of child
      behaviour. The overall quality of evidence used was high. AUTHORS' CONCLUSIONS:
      This update adds seven more trials to the original review, which contained four
      trials. At every dose analysed, levetiracetam significantly reduced focal seizure
      frequency relative to placebo. This indicates that levetiracetam can
      significantly reduce focal seizure frequency when it is used as an add-on
      treatment for both adults and children with drug-resistant focal epilepsy. As
      there was evidence of significant levels of statistical heterogeneity within this
      positive effect it is difficult to be precise about the relative magnitude of the
      effect. At a dose of 2000 mg, levetiracetam may be expected to be 3.9 times more
      effective than placebo; with 30% of adults being responders at this dose. At a
      dose of 60 mg/kg/day, levetiracetam may be expected to be 0.9 times more
      effective than placebo; with 25% of children being responders at this dose. When
      dose was ignored, children were better responders than adults by around 4% to
      13%. The results grossly suggest that one child or adult may respond to
      levetiracetam for every four or five children or adults, respectively, that have
      received levetiracetam rather than placebo. The drug seems to be well tolerated
      in both adults and children although non-specific changes in behaviour may be
      experienced in as high as 20% of children. This aspect of the adverse-effect
      profile of levetiracetam was analysed crudely and requires further investigation
      and validation. It seems reasonable to continue the use of levetiracetam in both
      adults and children with drug-resistant focal epilepsy. The results cannot be
      used to confirm longer-term or monotherapy effects of levetiracetam or its
      effects on generalised seizures. The conclusions are largely unchanged from those
      in the original review. The most significant contribution of this update is the
      addition of paediatric data into the analysis.

PMID- 22972057
TI  - Antipyretic measures for treating fever in malaria.
AB  - BACKGROUND: Fever is common in malaria, and drugs and sponging are widely used
      for symptomatic relief. Some researchers have suggested that fever reduction may
      prolong malaria illness. OBJECTIVES: We aimed to assess whether treatments to
      reduce fever in malaria influence the course of the illness. SEARCH METHODS: We
      searched the Cochrane Infectious Diseases Group Trial Register (June 2012), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 6,
      2012), MEDLINE (1966 to June 2012); EMBASE (1980 to June 2012) and LILACS (June
      2012). We contacted researchers and organisations working in the field to enable
      us identify other unpublished or ongoing trials. SELECTION CRITERIA: Randomized
      controlled trials of fever reduction measures in adults or children with
      confirmed malaria. DATA COLLECTION AND ANALYSIS: Inclusion criteria were
      independently applied by two authors. We extracted data from trials that met our
      pre-specified criteria using a standard data extraction form. Mean differences
      with 95% confidence intervals (CI) were calculated for continuous data. GRADE was
      used to evaluate and summarize the quality of the evidence. MAIN RESULTS: Ten
      randomized controlled trials with 990 participants including both adults and
      children met our inclusion criteria. All were small scale trials with
      methodological limitations and were conducted in a variety of patients. Some
      trials detected an impact of antipyretic drugs on fever clearance time, while
      others did not. Regarding parasite clearance,no clear influence of anti-pyresis
      was demonstrated (six trials, 423 participants, very low quality of evidence). No
      difference in the number or severity of adverse events between antipyretic drugs
      and control was detected. AUTHORS' CONCLUSIONS: We do not know whether
      antipyretics alter parasite clearance time. Whether further trials are worthwhile
      to investigate this or not would require a judgement of whether this was an
      important question to resolve using interventional trials.

PMID- 22972058
TI  - Clinical service organisation for heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is a serious, common condition associated
      with frequent hospitalisation. Several different disease management interventions
      (clinical service organisation interventions) for patients with CHF have been
      proposed. OBJECTIVES: To update the previously published review which assessed
      the effectiveness of disease management interventions for patients with CHF.
      SEARCH METHODS: A number of databases were searched for the updated review:
      CENTRAL, (the Cochrane Central Register of Controlled Trials) and DARE, on The
      Cochrane Library, ( Issue 1 2009); MEDLINE (1950-January 2009); EMBASE (1980
      January 2009); CINAHL (1982-January 2009); AMED (1985-January 2009). For the
      original review (but not the update) we had also searched: Science Citation Index
      Expanded (1981-2001); SIGLE (1980-2003); National Research Register (2003) and
      NHS Economic Evaluations Database (2001). We also searched reference lists of
      included studies for both the original and updated reviews. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) with at least six months follow up, comparing
      disease management interventions specifically directed at patients with CHF to
      usual care. DATA COLLECTION AND ANALYSIS: At least two reviewers independently
      extracted data and assessed study quality. Study authors were contacted for
      further information where necessary. Data were analysed and presented as odds
      ratios (OR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty five trials
      (5,942 people) were included. Interventions were classified by: (1) case
      management interventions (intense monitoring of patients following discharge
      often involving telephone follow up and home visits); (2) clinic interventions
      (follow up in a CHF clinic) and (3) multidisciplinary interventions (holistic
      approach bridging the gap between hospital admission and discharge home delivered
      by a team). The components, intensity and duration of the interventions varied,
      as did the 'usual care' comparator provided in different trials.Case management
      interventions were associated with reduction in all cause mortality at 12 months
      follow up, OR 0.66 (95% CI 0.47 to 0.91, but not at six months. No reductions
      were seen for deaths from CHF or cardiovascular causes. However, case management
      type interventions reduced CHF related readmissions at six month (OR 0.64, 95% CI
      0.46 to 0.88, P = 0.007) and 12 month follow up (OR 0.47, 95% CI 0.30 to 0.76).
      Impact of these interventions on all cause hospital admissions was not apparent
      at six months but was at 12 months (OR 0.75, 95% CI 0.57 to 0.99, I(2) = 58%).  
      CHF clinic interventions (for six and 12 month follow up) revealed non
      significant reductions in all cause mortality, CHF related admissions and all
      cause readmissions. Mortality was not reduced in the two studies that looked at
      multidisciplinary interventions. However, both all cause and CHF related
      readmissions were reduced (OR 0.46, 95% CI 0.46-0.69, and 0.45, 95% CI 0.28-0.72,
      respectively).  AUTHORS' CONCLUSIONS: Amongst CHF patients who have previously
      been admitted to hospital for this condition there is now good evidence that case
      management type interventions led by a heart failure specialist nurse reduces CHF
      related readmissions after 12 months follow up, all cause readmissions and all
      cause mortality.  It is not possible to say what the optimal components of these
      case management type interventions are, however telephone follow up by the nurse
      specialist was a common component.Multidisciplinary interventions may be
      effective in reducing both CHF and all cause readmissions. There is currently
      limited evidence to support interventions whose major component is follow up in a
      CHF clinic.

PMID- 22972059
TI  - Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular
      carcinoma in patients with chronic hepatitis B.
AB  - BACKGROUND: Chronic hepatitis B virus infection is a risk factor for development
      of hepatocellular carcinoma. Alpha-foetoprotein and liver ultrasonography are
      used to screen patients with chronic hepatitis B for hepatocellular carcinoma. It
      is uncertain whether screening is worthwhile. OBJECTIVES: To determine the
      beneficial and harmful effects of alpha-foetoprotein or ultrasound, or both, for
      screening of hepatocellular carcinoma in patients with chronic hepatitis B virus
      infection. SEARCH METHODS: Electronic searches were performed until December 2011
      in the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011),
      Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4) in The
      Cochrane Library, MEDLINE (1948 to 2011), EMBASE (1980 to 2011), Science Citation
      Index Expanded (1900 to 2011), Chinese Medical Literature Electronic Database
      (WanFang Data 1998 to 2011), and Chinese Knowledge Resource Integrated Database
      (1994 to 2011). SELECTION CRITERIA: All published reports of randomised trials on
      screening for liver cancer were eligible for inclusion, irrespective of language
      of publication. Studies were excluded when the hepatitis B status was uncertain,
      the screening tests were not sensitive or widely-used, or when the test was used
      for diagnosis of hepatocellular carcinoma rather than screening. DATA COLLECTION
      AND ANALYSIS: We independently analysed all the trials considered for inclusion.
      We wrote to the authors of one of the trials to obtain further information. MAIN
      RESULTS: Three randomised clinical trials were included in this review. All of
      them had a high risk of bias. One trial was conducted in Shanghai, China. There
      are several published reports on this trial, in which data were presented
      differently. According to the 2004 trial report, participants were randomised to
      screening every six months with alpha-foetoprotein and ultrasonography (n = 9373)
      versus no screening (n = 9443). We could not draw any definite conclusions from
      it. A second trial was conducted in Toronto, Canada. In this trial, there were
      1069 participants with chronic hepatitis B. The trial compared screening every
      six months with alpha-foetoprotein alone (n = 532) versus alpha-foetoprotein and
      ultrasound (n = 538) over a period of five years. This trial was designed as a
      pilot trial; the small number of participants and the rare events did not allow
      an effective comparison between the two modes of screening that were studied. The
      remaining trial, conducted in Taiwan and published as an abstract, was designed
      as a cluster randomised trial to determine the optimal interval for screening
      using alpha foetoprotein and ultrasound. Screening intervals of four months and
      12 months were compared in the two groups. Further details about the screening
      strategy were not available. The trial reported on cumulative four-year survival,
      cumulative three-year incidence of hepatocellular carcinoma, and mean tumour
      size. The cumulative four-year survival was not significantly different between
      the two screening intervals. The incidence of hepatocellular cancer was higher in
      the four-monthly screening group. The included trials did not report on adverse
      events. It appears that the sensitivity and specificity of the screening modes
      were poor, accounting for a substantial number of false-positive and false
      negative screening results. AUTHORS' CONCLUSIONS: There is not enough evidence to
      support or refute the value of alpha-foetoprotein or ultrasound screening, or
      both, of hepatitis B surface antigen (HBsAg) positive patients for hepatocellular
      carcinoma. More and better designed randomised trials are required to compare
      screening against no screening.

PMID- 22972060
TI  - Ionisers for chronic asthma.
AB  - BACKGROUND: Previous reports have shown that ion content in the air may have an
      effect on respiratory function. Results from studies which test the efficacy of
      air ionisers to reduce asthma symptoms are often inconclusive and their use as a
      treatment for asthma remains debatable. OBJECTIVES: We conducted a systematic
      review of the available evidence to determine the effectiveness of positive and
      negative ion generators in people with asthma. SEARCH METHODS: We searched the
      Cochrane Airways Group Specialised Register, Cochrane Central Register of
      Controlled Trials (CENTRAL) as well as the alternative medicine database AMED.
      Searches were current as of June 2012. SELECTION CRITERIA: Randomised controlled
      trials (parallel or crossover design studies) comparing ionisers with dummy
      ionisers (being negative or positive ion emitters), in children or adults with
      chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed titles and abstracts of studies and assessed trial quality. Study
      quality was determined using two methods:The Cochrane approach to allocation
      concealment and the five point Jadad scale. MAIN RESULTS: Six studies were
      selected for inclusion (106 participants). No results were combined as the
      studies were all of a crossover design.EFFECTS OF NEGATIVE ION GENERATORS (five
      studies) No study reported a significant difference in lung function between
      ionised and control air (morning Peak expiratory flow (PEF) - three studies;
      forced expiratory flow in one second (FEV1) - one study). There were no
      significant differences in symptoms or beta-2 agonist usage between ionised and
      control air in three studies.EFFECTS OF POSITIVE ION GENERATORS (one study) This
      study demonstrated that although positively ionised air was associated with a
      larger fall in FEV1 with exercise, this did not reach statistical significance.
      Baseline FEV1 was not demonstrated to be significantly different between
      treatment groups. AUTHORS' CONCLUSIONS: Based on the evidence currently available
      from randomised controlled trials, a recommendation cannot be given for the use
      of room air ionisers to reduce symptoms in patients with chronic asthma.

PMID- 22972061
TI  - Multifocal versus monofocal intraocular lenses after cataract extraction.
AB  - BACKGROUND: Good unaided distance visual acuity is now a realistic expectation
      following cataract surgery and intraocular lens (IOL) implantation. Near vision,
      however, still requires additional refractive power, usually in the form of
      reading glasses. Multiple optic (multifocal) IOLs are available which claim to
      allow good vision at a range of distances. It is unclear whether this benefit
      outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The
      objective of this review was to assess the effects of multifocal IOLs, including
      effects on visual acuity, subjective visual satisfaction, spectacle dependence,
      glare and contrast sensitivity, compared to standard monofocal lenses in people
      undergoing cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains
      the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012,
      Issue 2), MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March
      2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use
      any date or language restrictions in the electronic searches for trials. The
      electronic databases were last searched on 6 March 2012. We searched the
      reference lists of relevant articles and contacted investigators of included
      studies and manufacturers of multifocal IOLs for information about additional
      published and unpublished studies. SELECTION CRITERIA: All randomised controlled
      trials comparing a multifocal IOL of any type with a monofocal IOL as control
      were included. Both unilateral and bilateral implantation trials were included.
      DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial
      quality. Where possible, we pooled data from the individual studies using a
      random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen
      completed trials (1608 participants) and two ongoing trials were identified. All
      included trials compared multifocal and monofocal lenses but there was
      considerable variety in the make and model of lenses implanted. Overall we
      considered the trials at risk of performance and detection bias because it was
      difficult to mask patients and outcome assessors. It was also difficult to assess
      the role of reporting bias. There was moderate quality evidence that similar
      distance acuity is achieved with both types of lenses (pooled risk ratio (RR) for
      unaided visual acuity worse than 6/6: 0.98, 95% confidence interval (CI) 0.91 to
      1.05). There was also evidence that people with multifocal lenses had better near
      vision but methodological and statistical heterogeneity meant that we did not
      calculate a pooled estimate for effect on near vision. Total freedom from use of
      glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse
      subjective visual phenomena, particularly haloes, or rings around lights, were
      more prevalent and more troublesome in participants with the multifocal IOL and
      there was evidence of reduced contrast sensitivity with the multifocal lenses.
      AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision
      relative to monofocal IOLs. Whether that improvement outweighs the adverse
      effects of multifocal IOLs will vary between patients. Motivation to achieve
      spectacle independence is likely to be the deciding factor.

PMID- 22972062
TI  - Maternal glucose administration for facilitating tests of fetal wellbeing.
AB  - BACKGROUND: Antenatal maternal glucose administration has been suggested to
      improve the efficiency of antepartum fetal heart rate testing. OBJECTIVES: The
      objective of this review was to assess the merits or adverse effects of antenatal
      maternal glucose administration in conjunction with tests of fetal wellbeing.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (6 July 2012). SELECTION CRITERIA: All published and unpublished
      randomized controlled trials assessing the merits of antenatal maternal (oral or
      intravenous) glucose administration in conjunction with tests of fetal wellbeing.
      DATA COLLECTION AND ANALYSIS: Both review authors independently extracted data
      and assessed trial quality. Authors of published and unpublished trials were
      contacted for further information. MAIN RESULTS: A total of two trials, involving
      708 participants, were included. Antenatal maternal glucose administration did
      not decrease the incidence of non-reactive antenatal cardiotocography tests.
      AUTHORS' CONCLUSIONS: Antenatal maternal glucose administration has not been
      shown to reduce non-reactive cardiotocography. More trials are needed to further
      substantiate this and to determine not only the optimum dose, but also to
      evaluate the efficacy, predictive reliability, safety and perinatal outcome of
      glucose administration in conjunction with cardiotocography and also other tests
      of fetal wellbeing.

PMID- 22972063
TI  - Prophylactic antibiotics for preventing pneumococcal infection in children with
      sickle cell disease.
AB  - BACKGROUND: People with sickle cell disease are particularly susceptible to
      infection. Infants and very young children are especially vulnerable, and the 'Co
      operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100
      patient years of pneumococcal septicaemia in children under the age of three.
      Vaccines, including customary pneumococcal vaccines, may be of limited use in
      this age group. Therefore, prophylactic penicillin regimens may be advisable for
      this population. OBJECTIVES: To assess the effects of prophylactic antibiotic
      regimens for preventing pneumococcal infection in children with sickle cell
      disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Haemoglobinopathies Trials Register, which is comprised of
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference
      proceedings.Date of the most recent search: 28 March 2012. SELECTION CRITERIA:
      All randomised or quasi-randomised controlled trials comparing prophylactic
      antibiotics to prevent pneumococcal infection in children with sickle cell
      disease with placebo, no treatment or a comparator drug. DATA COLLECTION AND
      ANALYSIS: Both authors independently extracted data and assessed trial quality.
      MAIN RESULTS: Five trials were identified by the initial search, of which three
      trials met the inclusion criteria. All of the included trials showed a reduced
      incidence of infection in children with sickle cell disease (SS or Sbeta0Thal)
      receiving prophylactic penicillin. In trials which investigated initiation of
      penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI
      0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to
      2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection
      were found to be relatively low in children over the age of five. AUTHORS'
      CONCLUSIONS: Prophylactic penicillin significantly reduces risk of pneumococcal
      infection in children with homozygous sickle cell disease, and is associated with
      minimal adverse reactions. Further research may help to determine the ideal age
      to safely withdraw penicillin.

PMID- 22972064
TI  - Techniques and materials for skin closure in caesarean section.
AB  - BACKGROUND: Caesarean section is a common operation with no agreed upon standard
      regarding certain operative techniques or materials to use. With regard to skin
      closure, the skin incision can be re-approximated by a subcuticular suture
      immediately below the skin layer, by an interrupted suture, or by staples. A
      great variety of materials and techniques are used for skin closure after
      caesarean section and there is a need to identify which provide the best outcomes
      for women. OBJECTIVES: To compare the effects of skin closure techniques and
      materials on maternal and operative outcomes after caesarean section. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (10 January 2012). SELECTION CRITERIA: All randomized trials comparing
      different skin closure materials in caesareans were selected. Two review authors
      independently extracted the data. DATA COLLECTION AND ANALYSIS: We identified 18
      trials and included 10, but only eight trials contributed data. Three trials were
      not randomized controlled trials; three were ongoing; and one did not compare
      skin closure materials, but rather suture to suture and drain placement. MAIN
      RESULTS: The two methods of skin closure for caesarean that have been most often
      compared are non-absorbable staples and absorbable subcutaneous sutures. Compared
      with absorbable subcutaneous sutures, non-absorbable staples are associated with
      similar incidences of wound infection. Other important secondary outcomes, such
      as wound complications, were also similar between the groups in women with
      Pfannenstiel incisions. However, it is important to note, that for both of these
      outcomes (wound infection and wound complication), staples may have a
      differential effect depending on the type of skin incision, i.e., Pfannenstiel or
      vertical. Compared with absorbable subcutaneous sutures, non-absorbable staples
      are associated with an increased risk of skin separation, and therefore,
      reclosure. However, skin separation was variably defined across trials, and most
      staples were removed before four days postpartum. AUTHORS' CONCLUSIONS: There is
      currently no conclusive evidence about how the skin should be closed after
      caesarean section. Staples are associated with similar outcomes in terms of wound
      infection, pain and cosmesis compared with sutures, and these two are the most
      commonly studied methods for skin closure after caesarean section. If staples are
      removed on day three, there is an increased incidence of skin separation and the
      need for reclosure compared with absorbable sutures.

PMID- 22972065
TI  - Antidepressants for patients with tinnitus.
AB  - BACKGROUND: This is an update of a Cochrane review first published in The
      Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is
      described as the perception of sound or noise in the absence of real acoustic
      stimulation. It has been compared with chronic pain, and may be associated with
      depression or depressive symptoms which can affect quality of life and the
      ability to work. Antidepressant drugs have been used to treat tinnitus in
      patients with and without depressive symptoms. OBJECTIVES: To assess the
      effectiveness of antidepressants in the treatment of tinnitus and to ascertain
      whether any benefit is due to a direct tinnitus effect or a secondary effect due
      to treatment of concomitant depressive states. SEARCH METHODS: We searched the
      Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane
      Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; PsycINFO;
      CINAHL; Web of Science; BIOSIS; ICTRP and additional sources for published and
      unpublished trials. The date of the most recent search was 5 January 2012.
      SELECTION CRITERIA: Randomised controlled clinical studies of antidepressant
      drugs versus placebo in patients with tinnitus. DATA COLLECTION AND ANALYSIS: Two
      authors critically appraised the retrieved studies and extracted data
      independently. Where necessary we contacted study authors for further
      information. MAIN RESULTS: Six trials involving 610 patients were included. Trial
      quality was generally low. Four of the trials looked at the effect of tricyclic
      antidepressants on tinnitus, investigating 405 patients. One trial investigated
      the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120
      patients. One study investigated trazodone, an atypical antidepressant, versus
      placebo. Only the trial using the SSRI drug reached the highest quality standard.
      None of the other included trials met the highest quality standard, due to use of
      inadequate outcome measures, large drop-out rates or failure to separate the
      effects on tinnitus from the effects on symptoms of anxiety and depression. All
      the trials assessing tricyclic antidepressants suggested that there was a slight
      improvement in tinnitus but these effects may have been attributable to
      methodological bias. The trial that investigated the SSRI drug found no overall
      improvement in any of the validated outcome measures that were used in the study
      although there was possible benefit for a subgroup that received higher doses of
      the drug. This observation merits further investigation. In the trial
      investigating trazodone, the results showed an improvement in tinnitus intensity
      and in quality of life after treatment, but in neither case reached statistical
      significance. Reports of side effects including sedation, sexual dysfunction and
      dry mouth were common. AUTHORS' CONCLUSIONS: There is as yet insufficient
      evidence to say that antidepressant drug therapy improves tinnitus.

PMID- 22972066
TI  - Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is
      an uncommon progressive or relapsing paralysing disease caused by inflammation of
      the peripheral nerves. If the hypothesis that it is due to autoimmunity is
      correct, removal of autoantibodies in the blood by plasma exchange should be
      beneficial. OBJECTIVES: To evaluate the efficacy of plasma exchange in CIDP.
      SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized
      Register (14 May 2012), CENTRAL (2012, Issue 4), MEDLINE (January 1966 to May
      2012), EMBASE (January 1980 to May 2012), CINAHL Plus (January 1937 to May 2012)
      and LILACS (January 1982 to May 2012). We also scrutinised the bibliographies of
      the trials, and contacted the trial authors and other disease experts. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs in participants of
      any age comparing plasma exchange with sham treatment or no treatment. DATA
      COLLECTION AND ANALYSIS: Two authors selected the trials, extracted the data and
      assessed risk of bias independently. Where possible data were combined according
      to the methods of the Cochrane Neuromuscular Disease Review Group. MAIN RESULTS: 
      PRIMARY OUTCOME MEASURE: one cross-over trial including 18 participants showed
      two (95% confidence interval (CI) 0.8 to 3.0) points more improvement after four
      weeks on an 11-point disability scale with plasma exchange (10 exchanges over
      four weeks) than with sham exchange. Rapid deterioration after plasma exchange
      occurred in eight of 12 who had improved. SECONDARY OUTCOME MEASURES: when the
      results of this trial and another with 29 participants treated in a parallel
      group design trial were combined, there were 31 points (95% CI 16 to 45, maximum
      score 280) more improvement in an impairment scale after plasma exchange (six
      exchanges over three weeks) than after sham exchange. There were significant
      improvements in both trials in an electrophysiological measure, the proximally
      evoked compound muscle action potential, after three or four weeks. Non
      randomised evidence indicates that plasma exchange induces adverse events in 3%
      to 17% of procedures. These are sometimes serious. A trial showing no significant
      difference in the benefit between plasma exchange and intravenous immunoglobulin
      has been included in the Cochrane review of intravenous immunoglobulin for this
      condition. AUTHORS' CONCLUSIONS: Moderate to high quality evidence from two small
      trials showed that plasma exchange provides significant short-term improvement in
      disability, clinical impairment and motor nerve conduction velocity in CIDP but
      rapid deterioration may occur afterwards. Adverse events related to difficulty
      with venous access, use of citrate and haemodynamic changes are not uncommon.
      More research is needed to identify agents which will prolong the beneficial
      action of plasma exchange.

PMID- 22972067
TI  - Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.
AB  - BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve.
      Interventions during the resuscitation phase and treatment within the first hours
      after the event are critical. Experimental evidence suggests that therapeutic
      hypothermia is beneficial, and a number of clinical studies on this subject have
      been published. This review was originally published in 2009. OBJECTIVES: We
      performed a systematic review and meta-analysis to assess the effectiveness of
      therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome,
      survival and adverse events were our main outcomes. We aimed to perform
      individual patient data analysis, if data were available, and to form subgroups
      according to the cardiac arrest situation. SEARCH METHODS: We searched the
      following databases: the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2001, Issue 7); MEDLINE (1971 to July 2011); EMBASE (1987
      to July 2011); CINAHL (1988 to July 2011); PASCAL (2000 to July 2011); and BIOSIS
      (1989 to July 2011). The original search was performed in January 2007. SELECTION
      CRITERIA: We included all randomized controlled trials assessing the
      effectiveness of therapeutic hypothermia in patients after cardiac arrest,
      without language restrictions. Studies were restricted to adult populations
      cooled with any cooling method, applied within six hours of cardiac arrest. DATA
      COLLECTION AND ANALYSIS: Validity measures, the intervention, outcomes and
      additional baseline variables were entered into a database. Meta-analysis was
      only done for a subset of comparable studies with negligible heterogeneity. For
      these studies, individual patient data were available. MAIN RESULTS: We included
      four trials and one abstract reporting on 481 patients in the systematic review.
      The updated search resulted in no new studies to include. Quality of the included
      studies was good in three out of five studies. For the three comparable studies
      on conventional cooling methods all authors provided individual patient data.
      With conventional cooling methods, patients in the hypothermia group were more
      likely to reach a best cerebral performance categories (CPC) score of one or two
      (five point scale: 1 = good cerebral performance, to 5 = brain death) during the
      hospital stay (individual patient data; RR 1.55; 95% CI 1.22 to 1.96) and were
      more likely to survive to hospital discharge (individual patient data; RR 1.35;
      95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all
      studies, there was no significant difference in reported adverse events between
      hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to
      induce mild therapeutic hypothermia seem to improve survival and neurologic
      outcome after cardiac arrest. Our review supports the current best medical
      practice as recommended by the International Resuscitation Guidelines.

PMID- 22972068
TI  - Microwave thermotherapy for benign prostatic hyperplasia.
AB  - BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold
      standard treatment for alleviating urinary symptoms and improving urinary flow in
      men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity
      of TURP approaches 20%, and less invasive techniques have been developed for
      treating BPH. Preliminary data suggest that microwave thermotherapy, which
      delivers microwave energy to produce coagulation necrosis in prostatic tissue, is
      a safe, effective treatment for BPH. OBJECTIVES: To assess the therapeutic
      efficacy and safety of microwave thermotherapy techniques for treating men with
      symptomatic benign prostatic obstruction. SEARCH METHODS: Randomized controlled
      trials were identified from The Cochrane Library, MEDLINE, EMBASE, bibliographies
      of retrieved articles, reviews, technical reports, and by contacting relevant
      expert trialists and microwave manufacturers. SELECTION CRITERIA: All randomized
      controlled trials evaluating transurethral microwave thermotherapy (TUMT) for men
      with symptomatic BPH were eligible for this review. Comparison groups could
      include transurethral resection of the prostate, minimally invasive prostatectomy
      techniques, sham thermotherapy procedures, and medications. Outcome measures
      included urinary symptoms, urinary function, prostate volume, mortality,
      morbidity, and retreatment. Two review authors independently identified
      potentially relevant abstracts and then assessed the full papers for inclusion.
      DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted study
      design, baseline characteristics, and outcomes data and assessed methodological
      quality using a standard form. We attempted to obtain missing data from authors
      or sponsors, or both. MAIN RESULTS: In this update, we identified no new
      randomized comparisons of TUMT that provided evaluable effectiveness data.
      Fifteen studies involving 1585 patients met the inclusion criteria, including six
      comparisons of microwave thermotherapy with TURP, eight comparisons with sham
      thermotherapy procedures, and one comparison with an alpha-blocker. Study
      durations ranged from 3 to 60 months. The mean age of participants was 66.8 years
      and the baseline symptom scores and urinary flow rates, which did not differ
      across treatment groups, demonstrated moderately severe lower urinary tract
      symptoms. The pooled mean urinary symptom scores decreased by 65% with TUMT and
      by 77% with TURP. The weighted mean difference (WMD) with 95% confidence interval
      (CI) for the International Prostate Symptom Score (IPSS) was -1.00 (95% CI -2.03
      to -0.03), favoring TURP. The pooled mean peak urinary flow increased by 70% with
      TUMT and by 119% with TURP. The WMD for peak urinary flow was 5.08 mL/s (95% CI
      3.88 to 6.28 mL/s), favoring TURP. Compared to TURP, TUMT was associated with
      decreased risks for retrograde ejaculation, treatment for strictures, hematuria,
      blood transfusions, and the transurethral resection syndrome, but increased risks
      for dysuria, urinary retention, and retreatment for BPH symptoms. Microwave
      thermotherapy improved IPSS symptom scores (WMD -5.15, 95% CI -4.26 to -6.04) and
      peak urinary flow (WMD 2.01 mL/s, 95% CI 0.85 to 3.16) compared with sham
      procedures. Microwave thermotherapy also improved IPSS symptom scores (WMD -4.20,
      95% CI -3.15 to -5.25) and peak urinary flow (WMD 2.30 mL/s, 95% CI 1.47 to 3.13)
      in the one comparison with alpha-blockers. No studies evaluated the effects of
      symptom duration, patient characteristics, prostate-specific antigen levels, or
      prostate volume on treatment response. AUTHORS' CONCLUSIONS: Microwave
      thermotherapy techniques are effective alternatives to TURP and alpha-blockers
      for treating symptomatic BPH in men with no history of urinary retention or
      previous prostate procedures and prostate volumes between 30 to 100 mL. However,
      TURP provided greater symptom score and urinary flow improvements and reduced the
      need for subsequent BPH treatments compared to TUMT. Small sample sizes and
      differences in study design limit comparisons between devices with different
      designs and energy levels. The effects of symptom duration, patient
      characteristics, or prostate volume on treatment response are unknown.

PMID- 22972069
TI  - Medical versus surgical interventions for open angle glaucoma.
AB  - BACKGROUND: Open angle glaucoma (OAG) is a common cause of blindness. OBJECTIVES:
      To assess the effects of medication compared with initial surgery in adults with
      OAG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE,
      Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid
      OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012),
      Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982
      to August 2012), Biosciences Information Service (BIOSIS) (January 1969 to August
      2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January
      1937 to August 2012), OpenGrey (System for Information on Grey Literature in
      Europe) (www.opengrey.eu/), Zetoc, the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com) and the WHO International Clinical Trials Registry
      Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or
      language restrictions in the electronic searches for trials. We last searched the
      electronic databases on 1 August 2012. The National Research Register (NRR) was
      last searched in 2007 after which the database was archived. We also checked the
      reference lists of articles and contacted researchers in the field. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) comparing medications
      with surgery in adults with OAG. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted study
      authors for missing information. MAIN RESULTS: Four trials involving 888
      participants with previously untreated OAG were included. Surgery was Scheie's
      procedure in one trial and trabeculectomy in three trials. In three trials,
      primary medication was usually pilocarpine, in one trial it was a beta
      blocker.The most recent trial included participants with on average mild OAG. At
      five years, the risk of progressive visual field loss, based on a three unit
      change of a composite visual field score, was not significantly different
      according to initial medication or initial trabeculectomy (odds ratio (OR) 0.74,
      95% confidence interval (CI) 0.54 to 1.01). In an analysis based on mean
      difference (MD) as a single index of visual field loss, the between treatment
      group difference in MD was -0.20 decibel (dB) (95% CI -1.31 to 0.91). For a
      subgroup with more severe glaucoma (MD -10 dB), findings from an exploratory
      analysis suggest that initial trabeculectomy was associated with marginally less
      visual field loss at five years than initial medication, (mean difference 0.74 dB
      (95% CI -0.00 to 1.48). Initial trabeculectomy was associated with lower average
      intraocular pressure (IOP) (mean difference 2.20 mmHg (95% CI 1.63 to 2.77) but
      more eye symptoms than medication (P = 0.0053). Beyond five years, visual acuity
      did not differ according to initial treatment (OR 1.48, 95% CI 0.58 to 3.81).From
      three trials in more severe OAG, there is some evidence that medication was
      associated with more progressive visual field loss and 3 to 8 mmHg less IOP
      lowering than surgery. In the longer-term (two trials) the risk of failure of the
      randomised treatment was greater with medication than trabeculectomy (OR 3.90,
      95% CI 1.60 to 9.53; hazard ratio (HR) 7.27, 95% CI 2.23 to 25.71). Medications
      and surgery have evolved since these trials were undertaken.In three trials the
      risk of developing cataract was higher with trabeculectomy (OR 2.69, 95% CI 1.64
      to 4.42). Evidence from one trial suggests that, beyond five years, the risk of
      needing cataract surgery did not differ according to initial treatment policy (OR
      0.63, 95% CI 0.15 to 2.62).Methodological weaknesses were identified in all the
      trials. AUTHORS' CONCLUSIONS: Primary surgery lowers IOP more than primary
      medication but is associated with more eye discomfort. One trial suggests that
      visual field restriction at five years is not significantly different whether
      initial treatment is medication or trabeculectomy. There is some evidence from
      two small trials in more severe OAG, that initial medication (pilocarpine, now
      rarely used as first line medication) is associated with more glaucoma
      progression than surgery. Beyond five years, there is no evidence of a difference
      in the need for cataract surgery according to initial treatment.The clinical and
      cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2
      agonists and topical carbonic anhydrase inhibitors) compared with primary surgery
      is not known.Further RCTs of current medical treatments compared with surgery are
      required, particularly for people with severe glaucoma and in black ethnic
      groups. Outcomes should include those reported by patients. Economic evaluations
      are required to inform treatment policy.

PMID- 22972070
TI  - Empiric antibiotic coverage of atypical pathogens for community-acquired
      pneumonia in hospitalized adults.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is caused by various pathogens,
      traditionally divided into 'typical' and 'atypical'. Initial antibiotic treatment
      of CAP is usually empirical, customarily covering both typical and atypical
      pathogens. To date, no sufficient evidence exists to support this broad coverage,
      while limiting coverage is bound to reduce toxicity, resistance and expense.
      OBJECTIVES: The main objective was to estimate the mortality and proportion with
      treatment failure using regimens containing atypical antibiotic coverage compared
      to those that had typical coverage only. Secondary objectives included the
      assessment of adverse events. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) Issue 3, 2012 which includes the Acute
      Respiratory Infection Group's Specialized Register, MEDLINE (January 1966 to
      April week 1, 2012) and EMBASE (January 1980 to April 2012). SELECTION CRITERIA:
      Randomized controlled trials (RCTs) of adult patients hospitalized due to CAP,
      comparing antibiotic regimens with atypical coverage (quinolones, macrolides,
      tetracyclines, chloramphenicol, streptogramins or ketolides) to a regimen without
      atypical antibiotic coverage. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the risk of bias and extracted data from included trials.
      We estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assessed
      heterogeneity using a Chi(2) test. MAIN RESULTS: We included 28 trials,
      encompassing 5939 randomized patients. The atypical antibiotic was administered
      as monotherapy in all but three studies. Only one study assessed a beta-lactam
      combined with a macrolide compared to the same beta-lactam. There was no
      difference in mortality between the atypical arm and the non-atypical arm (RR
      1.14; 95% CI 0.84 to 1.55), RR < 1 favors the atypical arm. The atypical arm
      showed an insignificant trend toward clinical success and a significant advantage
      to bacteriological eradication, which disappeared when evaluating
      methodologically high quality studies alone. Clinical success for the atypical
      arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and
      non-significantly lower for pneumococcal pneumonia. There was no significant
      difference between the groups in the frequency of (total) adverse events, or
      those requiring discontinuation of treatment. However, gastrointestinal events
      were less common in the atypical arm (RR 0.70; 95% CI 0.53 to 0.92). Although the
      trials assessed different antibiotics, no significant heterogeneity was detected
      in the analyses. AUTHORS' CONCLUSIONS: No benefit of survival or clinical
      efficacy was shown with empirical atypical coverage in hospitalized patients with
      CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to
      beta-lactams. Further trials, comparing beta-lactam monotherapy to the same
      combined with a macrolide, should be performed.

PMID- 22972071
TI  - Interventions for recurrent idiopathic epistaxis (nosebleeds) in children.
AB  - BACKGROUND: Recurrent idiopathic epistaxis (nosebleeds) in children is repeated
      nasal bleeding in patients up to the age of 16 for which no specific cause has
      been identified. Although nosebleeds are very common in children, and most cases
      are self limiting or settle with simple measures (such as pinching the nose),
      more severe recurrent cases can require treatment from a healthcare professional.
      However, there is no consensus on the effectiveness of the different clinical
      interventions currently used in managing this condition. OBJECTIVES: To assess
      the effects of different interventions for the management of recurrent idiopathic
      epistaxis in children. SEARCH METHODS: We searched the Cochrane Ear, Nose and
      Throat Disorders Group Trials Register; the Cochrane Central Register of
      Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS
      Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for
      published and unpublished trials. The date of the most recent search was 5 March
      2012. SELECTION CRITERIA: We identified all randomised controlled trials (RCTs)
      (with or without blinding) in which any surgical or medical intervention for the
      treatment of recurrent idiopathic epistaxis in children was evaluated in
      comparison with either no treatment, a placebo or another intervention, and in
      which the frequency and severity of episodes of nasal bleeding following
      treatment was stated or calculable. The two authors reviewed the full-text
      articles of all retrieved trials of possible relevance and applied the inclusion
      criteria independently. DATA COLLECTION AND ANALYSIS: We graded trials for risk
      of bias using the Cochrane approach. One author performed data extraction in a
      standardised manner and this was rechecked by the other author. Where necessary
      we contacted investigators to obtain missing information. We did not undertake a
      meta-analysis because of the heterogeneity of the treatments, procedures and
      quality of the included trials. A narrative overview of the results is therefore
      presented. MAIN RESULTS: Five studies (four RCTs and one quasi-randomised
      controlled trial) involving 468 participants satisfied the inclusion criteria.
      The identified RCTs compared 0.5% neomycin + 0.1% chlorhexidine (Naseptin(r))
      cream with no treatment, Vaseline(r) petroleum jelly with no treatment, 75% with
      95% silver nitrate nasal cautery, and silver nitrate cautery combined with
      Naseptin(r) against Naseptin(r) alone; the quasi-randomised controlled trial
      compared Naseptin(r) antiseptic cream with silver nitrate cautery. Overall
      results were inconclusive, with no statistically significant difference found
      between the compared treatments upon completion of the trials, however 75% silver
      nitrate was more effective than 95% silver nitrate at two weeks following
      application. The group treated with 75% silver nitrate had 88% complete
      resolution of epistaxis compared to 65% in the group treated with 95% silver
      nitrate (P = 0.01). No serious adverse effects were reported from any of the
      interventions, although children receiving silver nitrate cautery reported that
      it was a painful experience (despite the use of local anaesthetic). The pain
      scores were significantly less in those treated with 75% silver nitrate, the mean
      score being 1 compared to a mean score of 5 in those treated with 95% silver
      nitrate; this was statistically significant (P = 0.001).We carried out a 'Risk of
      bias' assessment of each study according to the Cochrane methodology and judged
      that two randomised controlled trials had a low risk of bias, two had an unclear
      risk of bias and the quasi-randomised controlled trial had a high risk of bias.
      AUTHORS' CONCLUSIONS: The optimal management of children with recurrent
      idiopathic epistaxis is unknown, however if silver nitrate nasal cautery is
      undertaken 75% is preferable to 95% as it is more effective in the short term and
      causes less pain. High-quality randomised controlled trials comparing
      interventions either with placebo or no treatment, and with a follow-up period of
      at least a year, are needed to assess the relative merits of the various
      treatments currently in use.

PMID- 22972072
TI  - Incentive spirometry for preventing pulmonary complications after coronary artery
      bypass graft.
AB  - BACKGROUND: Incentive spirometry (IS) is a treatment technique that uses a
      mechanical device to reduce pulmonary complications during postoperative care.
      This is an update of a Cochrane review first published in 2007. OBJECTIVES:
      Update the previously published systematic review to compare the effects of IS
      for preventing postoperative pulmonary complications in adults undergoing
      coronary artery bypass graft (CABG). SEARCH METHODS: We searched CENTRAL and DARE
      on The Cochrane Library (Issue 2 of 4 2011), MEDLINE OVID (1948 to May 2011),
      EMBASE (1980 to Week 20 2011), LILACS (1982 to July 2011) , the Physiotherapy
      Evidence Database (PEDro) (1980 to July 2011), Allied & Complementary Medicine
      (AMED) (1985 to May 2011), CINAHL (1982 to May 2011). SELECTION CRITERIA:
      Randomised controlled trials comparing IS with any type of prophylactic
      physiotherapy for prevention of postoperative pulmonary complications in adults
      undergoing CABG. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      evaluated trial quality using the guidelines of the Cochrane Handbook for
      Systematic Reviews and extracted data from included trials. For continuous
      outcomes, we used the generic inverse variance method for meta-analysis and for
      dichotomous data we used the Peto Odds Ratio. MAIN RESULTS: This update included
      592 participants from seven studies (two new and one that had been excluded in
      the previous review in 2007. There was no evidence of a difference between groups
      in the incidence of any pulmonary complications and functional capacity between
      treatment with IS and treatment with physical therapy, positive pressure
      breathing techniques (including continuous positive airway pressure (CPAP),
      bilevel positive airway pressure (BiPAP) and intermittent positive pressure
      breathing (IPPB), active cycle of breathing techniques (ACBT) or preoperative
      patient education. Patients treated with IS had worse pulmonary function and
      arterial oxygenation compared with positive pressure breathing. Based on these
      studies there was no improvement in the muscle strength between groups who
      received IS demonstrated by maximal inspiratory pressure and maximal expiratory
      pressure . AUTHORS' CONCLUSIONS: Our update review suggests there is no evidence
      of benefit from IS in reducing pulmonary complications and in decreasing the
      negative effects on pulmonary function in patients undergoing CABG. In view of
      the modest number of patients studied, methodological shortcomings and poor
      reporting of the included trials, these results should still be interpreted
      cautiously. An appropriately powered trial of high methodological rigour is
      needed to determine if there are patients who may derive benefit from IS
      following CABG.

PMID- 22972073
TI  - WITHDRAWN: Herbal medicines for advanced colorectal cancer.

PMID- 22972074
TI  - Prophylactic oral betamimetics for reducing preterm birth in women with a twin
      pregnancy.
AB  - BACKGROUND: Twin pregnancies are associated with a high risk of neonatal
      mortality and morbidity due to an increased rate of preterm birth. Betamimetics
      can decrease contraction frequency or delay preterm birth in singleton
      pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a
      twin pregnancy is unproven. OBJECTIVES: To assess the effectiveness of
      prophylactic oral betamimetics for the prevention of preterm labour and birth for
      women with twin pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy
      and Childbirth Group Trials Register (31 January 2012), the Central Register of
      Controlled Trials (The Cochrane Library 2012, Issue 2), MEDLINE (January 1966 to
      1 February 2012) and EMBASE (January 1985 to 1 February 2012). SELECTION
      CRITERIA: Randomised controlled trials in twin pregnancies comparing oral
      betamimetics with placebo or any intervention with the specific aim of preventing
      preterm birth. Quasi-randomised controlled trials, cluster-randomised trials and
      cross-over trials were not included. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trials for inclusion and trial quality. Two review
      authors extracted data. Data were checked for accuracy. MAIN RESULTS: Six trials
      (374 twin pregnancies) were included, but only five trials (344 twin pregnancies)
      contributed data. All trials compared oral betamimetics with placebo.Betamimetics
      reduced the incidence of preterm labour (one trial, 50 twin pregnancies, risk
      ratio (RR) 0.40; 95% confidence interval (CI) 0.19 to 0.86). However,
      betamimetics did not reduce preterm birth less than 37 weeks' gestation (four
      trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10) or less than 34
      weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50).
      Mean neonatal birthweight in the betamimetic group was significantly higher than
      in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95%
      CI 22.2 to 200.2). Nevertheless, there was no evidence of an effect of
      betamimetics in reduction of low birthweight (two trials, 366 neonates, average
      RR 1.19; 95% CI 0.77 to 1.85, random-effects) or small-for-gestational age
      neonates (two trials, 178 neonates, RR 0.92; 95% CI 0.52 to 1.65). Two trials
      (388 neonates) showed that betamimetics significantly reduced the incidence of
      respiratory distress syndrome but the difference was not significant when the
      analysis was adjusted for correlation of babies from twins. Three trials (452
      neonates) showed no evidence of an effect of betamimetics in reducing neonatal
      mortality (RR 0.80; 95% CI 0.35 to 1.82). AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support or refute the use of prophylactic oral
      betamimetics for preventing preterm birth in women with a twin pregnancy.

PMID- 22972075
TI  - Vitamin K for upper gastrointestinal bleeding in patients with acute or chronic
      liver diseases.
AB  - BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of
      morbidity and mortality in the course of liver cirrhosis. Several treatments are
      used for upper gastrointestinal bleeding in patients with liver diseases. One of
      them is vitamin K administration, but it is not known whether it benefits or
      harms patients with acute or chronic liver disease and upper gastrointestinal
      bleeding. OBJECTIVES: To assess the beneficial and harmful effects of vitamin K
      for patients with acute or chronic liver disease and upper gastrointestinal
      bleeding. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group
      Controlled Trials Register (12 June 2012), the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (Issue 5 of 12, 2012),
      MEDLINE (Ovid SP) (1946 to 12 June 2012), EMBASE (Ovid SP) (1974 to 12 June
      2012), Science Citation Index EXPANDED (1900 to 12 June 2012), and LILACS (1982
      to 19 June 2012). Additional randomised trials were sought from two registries of
      clinical trials: the Clinical Trials Search Portal of the WHO, and the
      Metaregister of Controlled Trials. We looked through the reference lists of the
      retrieved publications and review articles. SELECTION CRITERIA: Randomised
      clinical trials irrespective of blinding, language, or publication status for
      assessment of benefits and harms. Observational studies were considered for
      assessment of harms only. DATA COLLECTION AND ANALYSIS: Data from randomised
      clinical trials were to be summarised by standard Cochrane Collaboration
      methodologies. MAIN RESULTS: We could not find any randomised trials on vitamin K
      for upper gastrointestinal bleeding in patients with liver diseases in which we
      could assess benefits and harms. We could not identify quasi-randomised studies,
      historically controlled or observational studies in which we could assess harms.
      AUTHORS' CONCLUSIONS: This updated review found no randomised clinical trials on
      the benefits and harms of vitamin K for upper gastrointestinal bleeding in
      patients with liver diseases. The effects of vitamin K need to be tested in
      randomised clinical trials. Until randomised clinical trials are conducted to
      assess the trade off between benefits and harms, we cannot recommend nor refute
      vitamin K for upper gastrointestinal bleeding in patients with liver diseases.

PMID- 22972076
TI  - Early erythropoietin for preventing red blood cell transfusion in preterm and/or
      low birth weight infants.
AB  - BACKGROUND: Low plasma levels of erythropoietin (EPO) in preterm infants provide
      a rationale for the use of EPO to prevent or treat anaemia. OBJECTIVES: To assess
      the effectiveness and safety of early initiation of EPO in reducing red blood
      cell (RBC) transfusions in preterm and/or low birth weight infants. SEARCH
      METHODS: The Cochrane Central Register of Controlled Trials (The Cochrane
      Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published
      in Pediatric Research and reference lists of identified trials and reviews were
      searched through July 2009. Searches were repeated in March 2012 including
      searches of Pediatric Academic Societies Annual meetings 2000 to 2012
      (Abstracts2View(TM)) and clinical trials registries (clinicaltrials.gov;
      controlled-trials.com; and who.int/ictrp). SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials of early (< eight days of age) initiation of
      EPO treatment versus placebo or no intervention in preterm and/or low birth
      weight neonates. DATA COLLECTION AND ANALYSIS: Data collection and analysis were
      accomplished using the methods of the Neonatal Cochrane Review Group. MAIN
      RESULTS: The May 2012 update did not identify any new studies for inclusion. A
      number of randomised controlled trials were excluded as they compared one EPO
      dosing regimen with another, did not provide the numbers of infants randomised to
      the EPO and the placebo group, or the dose of EPO was not stated. The update
      includes 27 studies that enrolled 2293 preterm infants. Early EPO reduced the
      risk of the "use of one or more RBC transfusions" [typical risk ratio (RR); 0.80
      (95% confidence interval (CI) 0.75 to 0.86); typical risk difference (RD) -0.13,
      (95% CI -0.17 to -0.09); number needed to benefit (NNTB) = eight, (95% CI 6 to
      11); 16 studies, 1,825 infants].There was moderate heterogeneity for this outcome
      [RR (P = 0.004; I(2) = 56.7%); RD (P = 0.003; I(2) = 56.0%)].A total of six
      studies enrolling 515 infants reported on the total volume of red blood cells
      transfused per infant. The significant typical mean difference (MD) was a
      reduction of 6 mL/kg of blood transfused (mL/kg) per infant (95% CI -11 to - 1).
      There was moderate heterogeneity for this outcome (P = 0.02; I(2) = 63.0%). The
      results from 14 studies enrolling 1131 infants reported on the number of red
      blood cell transfusions per infant. The significant typical MD for number of red
      blood cell transfusions per infant was -0.33, (95% CI -0.48 to -0.18). There was
      high heterogeneity for this outcome (P = 0.00001, I(2) = 78%). Two studies
      enrolling 188 infants reported on the number of donors to whom the infant was
      exposed; the MD was significantly reduced -0.63, (-1.07 to -0.19). There was no
      heterogeneity for this outcome (P = 0.59; I(2) = 0%).There was a significant
      increase in the risk of stage >= 3 retinopathy of prematurity (ROP) in the early
      EPO group [typical RR; 1.65, (95% CI 1.12 to 2.43); typical RD; 0.05 (95% CI 0.01
      to 0.08); number needed to harm (NNTH); 20, (95% CI 13 to 100); eight studies,
      984 infants]. There was no heterogeneity for this outcome for RR (P = 0.87; I(2)
      = 0%), but there was moderate heterogeneity for RD (P = 0.006; I(2) = 65%). The
      rates for mortality and other neonatal morbidities were not significantly changed
      by early EPO treatment nor were neurodevelopmental outcomes at 18 to 22 months in
      the small number of infants tested to-date. AUTHORS' CONCLUSIONS: Early
      administration of EPO reduces the use of RBC transfusions and the volume of RBCs
      transfused. These small reductions are of limited clinical importance. Donor
      exposure is probably not avoided since most studies included infants who had
      received RBC transfusions prior to trial entry. There was a significant increase
      in the rate of ROP (stage >= 3). Early EPO does not significantly decrease or
      increase any of the other important adverse outcomes. Ongoing research should
      deal with the issue of ROP and evaluate the current clinical practice that will
      limit donor exposure. Due to the limited benefits and the increased risk of ROP,
      early administration of EPO is not recommended. Evidence is lacking for the
      possible neuro protective role of EPO in preterm infants. This topic will be
      reviewed in separate Cochrane reviews for preterm and term and late preterm
      infants.

PMID- 22972077
TI  - Late erythropoietin for preventing red blood cell transfusion in preterm and/or
      low birth weight infants.
AB  - BACKGROUND: Low plasma levels of erythropoietin (EPO) in preterm infants provide
      a rationale for the use of EPO to prevent or treat anaemia. OBJECTIVES: To assess
      the effectiveness and safety of late initiation of EPO (initiated at eight days
      after birth or later) in reducing the use of red blood cell (RBC) transfusions in
      preterm and/or low birth weight infants. SEARCH METHODS: For this update MEDLINE,
      EMBASE, CINAHL, and The Cochrane Library were searched in March 2012. Additional
      searches included the Pediatric Academic Societies Annual Meetings from 2000 to
      2012 (Abstracts2 View(TM)) and clinical trials registries (clinicaltrials.gov;
      controlled-trials.com; and who.int/ictrp). SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials of late initiation of EPO treatment (started
      at >= eight days of age) versus placebo or no intervention in preterm (< 37
      weeks) and/or low birth weight (< 2500 g) neonates. DATA COLLECTION AND ANALYSIS:
      Data collection and analyses were performed in accordance with the methods of the
      Cochrane Neonatal Review Group. MAIN RESULTS: In this 2012 update one new study
      for inclusion was identified. Twenty-eight studies enrolling 1361 preterm infants
      in 21 countries were included. Most trials were of small sample size. The meta
      analysis showed a significant effect on the use of one or more RBC transfusions
      [typical risk ratio (RR); 0.66 (95% confidence interval (CI); 0.59 to 0.74);
      typical risk difference (RD) -0.21 (95% CI; -0.26 to -0.16); typical number
      needed to benefit (NNTB) of 5 (95% CI 4 to 6) 19 studies, 912 infants]. There was
      moderate heterogeneity for this outcome [for RR (P < 0.00001; I(2) = 74.0%); for
      RD (P = 0.0006; I(2) = 58.9%)]. Similar results were obtained in secondary
      analyses based on different combinations of high/low doses of EPO and iron
      supplementation. In this update there was no significant reduction in the total
      volume (mL/kg) of blood transfused per infant [typical MD -1.61mL/kg (95% CI 
      5.78 to 2.57); 5 studies, 197 infants] There was high heterogeneity for this
      outcome (P = 0.00001, I(2) = 92%). There was a significant reduction in the
      number of transfusions per infant (nine studies enrolling 567 infants); [typical
      MD -0.78 (-0.97 to -0.59)]. Three studies including 331 patients reported on
      retinopathy of prematurity (ROP) (all stages), with a typical RR 0.79 (95% CI
      0.57 to 1.10) and a typical RD of -0.05 (95% CI -0.13 to 0.02). This outcome was
      not statistically significantly different between the groups. There was no
      heterogeneity for this outcome for either RR (P = 0.41; I(2) = 0%) or RD (P =
      0.43; I(2) = 0%). Two trials enrolling 212 patients reported on severe ROP (stage
      3 or greater). The typical RR was 0.83 (95% CI 0.23 to 2.98) and the typical RD
      was -0.01 (95% CI -0.06 to 0.05); neither were statistically significant. There
      was no heterogeneity for this outcome for either RR (P = 0.29; I(2) = 9.3%) or RD
      (P = 0.36; I(2) = 0%).There were no significant differences in other clinical
      outcomes. Long-term neurodevelopmental outcomes were not reported. AUTHORS'
      CONCLUSIONS: Late administration of EPO reduces the use of one or more RBC
      transfusions, the number of RBC transfusions per infant but not the total volume
      of RBCs transfused per infant. Any donor exposure is likely not avoided as most
      studies included infants who had received RBC transfusions prior to trial entry.
      Late EPO does not significantly reduce or increase any clinically important
      adverse outcomes. Further research of the use of late EPO treatment to prevent
      donor exposure is not indicated. Research efforts should focus on limiting donor
      exposure during the first few days of life in sick neonates, when RBC
      requirements are most likely to be required and cannot be prevented by late EPO
      treatment.

PMID- 22972078
TI  - Massage for mechanical neck disorders.
AB  - BACKGROUND: The prevalence of mechanical neck disorders (MND) is known to be both
      a hindrance to individuals and costly to society. As such, massage is widely used
      as a form of treatment for MND. OBJECTIVES: To assess the effects of massage on
      pain, function, patient satisfaction, global perceived effect, adverse effects
      and cost of care in adults with neck pain versus any comparison at immediate post
      treatment to long-term follow-up. SEARCH METHODS: We searched The Cochrane
      Library (CENTRAL), MEDLINE, EMBASE, MANTIS, CINAHL, and ICL databases from date
      of inception to 4 Feburary 2012. SELECTION CRITERIA: Studies using random
      assignment were included. DATA COLLECTION AND ANALYSIS: Two review authors
      independently conducted citation identification, study selection, data
      abstraction and methodological quality assessment. Using a random-effects model,
      we calculated the risk ratio and standardised mean difference. MAIN RESULTS:
      Fifteen trials met the inclusion criteria. The overall methodology of all the
      trials assessed was either low or very low GRADE level. None of the trials were
      of strong to moderate GRADE level. The results showed very low level evidence
      that certain massage techniques (traditional Chinese massage, classical and
      modified strain/counter strain technique) may have been more effective than
      control or placebo treatment in improving function and tenderness. There was very
      low level evidence that massage may have been more beneficial than education in
      the short term for pain bothersomeness. Along with that, there was low level
      evidence that ischaemic compression and passive stretch may have been more
      effective in combination rather than individually for pain reduction. The
      clinical applicability assessment showed that only 4/15 trials adequately
      described the massage technique. The majority of the trials assessed outcomes at
      immediate post-treatment, which is not an adequate time to assess clinical
      change. Due to the limitations in the quality of existing studies, we were unable
      to make any firm statement to guide clinical practice. We noted that only four of
      the 15 studies reported side effects. All four studies reported post-treatment
      pain as a side effect and one study (Irnich 2001) showed that 22% of the
      participants experienced low blood pressure following treatment. AUTHORS'
      CONCLUSIONS: No recommendations for practice can be made at this time because the
      effectiveness of massage for neck pain remains uncertain.As a stand-alone
      treatment, massage for MND was found to provide an immediate or short-term
      effectiveness or both in pain and tenderness. Additionally, future research is
      needed in order to assess the long-term effects of treatment and treatments
      provided on more than one occasion.

PMID- 22972079
TI  - Antibiotics for community-acquired lower respiratory tract infections secondary
      to Mycoplasma pneumoniae in children.
AB  - BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an
      important cause of community-acquired lower respiratory tract infection (LRTI) in
      children. Pulmonary manifestations are typically tracheobronchitis or pneumonia
      but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and
      non-asthmatic individuals. Although antibiotics are used to treat LRTIs, a review
      of several major textbooks offers conflicting advice for using antibiotics in the
      management of M. pneumoniae LRTI in children. OBJECTIVES: To determine whether
      antibiotics are effective in the treatment of childhood LRTI secondary to M.
      pneumoniae infections acquired in the community. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's
      Specialised Register, MEDLINE (1966 to February week 5, 2012) and EMBASE (1980 to
      March 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      antibiotics commonly used for treating M. pneumoniae (i.e. macrolide,
      tetracycline or quinolone classes) versus placebo, or antibiotics from any other
      class in the treatment of children under 18 years of age with community-acquired
      LRTI secondary to M. pneumoniae. DATA COLLECTION AND ANALYSIS: The review authors
      independently selected trials for inclusion and assessed methodological quality.
      We extracted and analysed relevant data separately. We resolved disagreements by
      consensus. MAIN RESULTS: A total of 1912 children were enrolled from seven
      studies. Data interpretation was limited by the inability to extract data that
      referred to children with M. pneumoniae. In most studies, clinical response did
      not differ between children randomised to a macrolide antibiotic and children
      randomised to a non-macrolide antibiotic. In one controlled study (of children
      with recurrent respiratory infections, whose acute LRTI was associated with
      Mycoplasma, Chlamydia or both by polymerase chain reaction, and/or paired sera)
      100% of children treated with azithromycin had clinical resolution of their
      illness compared to 77% not treated with azithromycin at one month. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to draw any specific conclusions
      about the efficacy of antibiotics for this condition in children (although one
      trial suggests macrolides may be efficacious in some children with LRTI secondary
      to Mycoplasma). The use of antibiotics has to be balanced with possible adverse
      events. There is still a need for high quality, double-blinded RCTs to assess the
      efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in
      children.

PMID- 22972080
TI  - Preoperative bathing or showering with skin antiseptics to prevent surgical site
      infection.
AB  - BACKGROUND: Surgical site infections (SSIs) are wound infections that occur after
      invasive (surgical) procedures. Preoperative bathing or showering with an
      antiseptic skin wash product is a well-accepted procedure for reducing skin
      bacteria (microflora). It is less clear whether reducing skin microflora leads to
      a lower incidence of surgical site infection. OBJECTIVES: To review the evidence
      for preoperative bathing or showering with antiseptics for preventing hospital
      acquired (nosocomial) surgical site infections. SEARCH METHODS: For this fourth
      update we searched the Cochrane Wounds Group Specialised Register (searched 29
      June 2012); the Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2012 Issue 6); Ovid MEDLINE (2010 to June Week 3 2012), Ovid MEDLINE (In
      Process & Other Non-Indexed Citations June 27, 2012); Ovid EMBASE (2010 to 2012
      Week 25), EBSCO CINAHL (1882 to 21 June 2012) and reference lists of articles.
      SELECTION CRITERIA: Randomised controlled trials comparing any antiseptic
      preparation used for preoperative full-body bathing or showering with non
      antiseptic preparations in people undergoing surgery. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed studies for selection, risk
      of bias and extracted data. Study authors were contacted for additional
      information. MAIN RESULTS: We did not identify any new trials for inclusion in
      this fourth update. Seven trials involving a total of 10,157 participants were
      included. Four of the included trials had three comparison groups. The antiseptic
      used in all trials was 4% chlorhexidine gluconate (Hibiscrub/Riohex). Three
      trials involving 7791 participants compared chlorhexidine with a placebo. Bathing
      with chlorhexidine compared with placebo did not result in a statistically
      significant reduction in SSIs; the relative risk of SSI (RR) was 0.91 (95%
      confidence interval (CI) 0.80 to 1.04). When only trials of high quality were
      included in this comparison, the RR of SSI was 0.95 (95%CI 0.82 to 1.10). Three
      trials of 1443 participants compared bar soap with chlorhexidine; when combined
      there was no difference in the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Three
      trials of 1192 patients compared bathing with chlorhexidine with no washing, one
      large study found a statistically significant difference in favour of bathing
      with chlorhexidine (RR 0.36, 95%CI 0.17 to 0.79). The smaller studies found no
      difference between patients who washed with chlorhexidine and those who did not
      wash preoperatively. AUTHORS' CONCLUSIONS: This review provides no clear evidence
      of benefit for preoperative showering or bathing with chlorhexidine over other
      wash products, to reduce surgical site infection. Efforts to reduce the incidence
      of nosocomial surgical site infection should focus on interventions where effect
      has been demonstrated.

PMID- 22972081
TI  - Home safety education and provision of safety equipment for injury prevention.
AB  - BACKGROUND: In industrialised countries injuries (including burns, poisoning or
      drowning) are the leading cause of childhood death and steep social gradients
      exist in child injury mortality and morbidity. The majority of injuries in pre
      school children occur at home but there is little meta-analytic evidence that
      child home safety interventions reduce injury rates or improve a range of safety
      practices, and little evidence on their effect by social group. OBJECTIVES: We
      evaluated the effectiveness of home safety education, with or without the
      provision of low cost, discounted or free equipment (hereafter referred to as
      home safety interventions), in reducing child injury rates or increasing home
      safety practices and whether the effect varied by social group. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2009,
      Issue 2) in The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid),
      ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of
      Science: Social Sciences Citation Index (SSCI), ISI Web of Science: Conference
      Proceedings Citation Index- Science (CPCI-S), CINAHL (EBSCO) and DARE (2009,
      Issue 2) in The Cochrane Library. We also searched websites and conference
      proceedings and searched the bibliographies of relevant studies and previously
      published reviews. We contacted authors of included studies as well as relevant
      organisations. The most recent search for trials was May 2009. SELECTION
      CRITERIA: Randomised controlled trials (RCTs), non-randomised controlled trials
      and controlled before and after (CBA) studies where home safety education with or
      without the provision of safety equipment was provided to those aged 19 years and
      under, and which reported injury, safety practices or possession of safety
      equipment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study
      quality and extracted data. We attempted to obtain individual participant level
      data (IPD) for all included studies and summary data and IPD were simultaneously
      combined in meta-regressions by social and demographic variables. Pooled
      incidence rate ratios (IRR) were calculated for injuries which occurred during
      the studies, and pooled odds ratios were calculated for the uptake of safety
      equipment or safety practices, with 95% confidence intervals. MAIN RESULTS:
      Ninety-eight studies, involving 2,605,044 people, are included in this review.
      Fifty-four studies involving 812,705 people were comparable enough to be included
      in at least one meta-analysis. Thirty-five (65%) studies were RCTs. Nineteen
      (35%) of the studies included in the meta-analysis provided IPD.There was a lack
      of evidence that home safety interventions reduced rates of thermal injuries or
      poisoning. There was some evidence that interventions may reduce injury rates
      after adjusting CBA studies for baseline injury rates (IRR 0.89, 95% CI 0.78 to
      1.01). Greater reductions in injury rates were found for interventions delivered
      in the home (IRR 0.75, 95% CI 0.62 to 0.91), and for those interventions not
      providing safety equipment (IRR 0.78, 95% CI 0.66 to 0.92).Home safety
      interventions were effective in increasing the proportion of families with safe
      hot tap water temperatures (OR 1.41, 95% CI 1.07 to 1.86), functional smoke
      alarms (OR 1.81, 95% CI 1.30 to 2.52), a fire escape plan (OR 2.01, 95% CI 1.45
      to 2.77), storing medicines (OR 1.53, 95% CI 1.27 to 1.84) and cleaning products
      (OR 1.55, 95% CI 1.22 to 1.96) out of reach, having syrup of ipecac (OR 3.34, 95%
      CI 1.50 to 7.44) or poison control centre numbers accessible (OR 3.30, 95% CI
      1.70 to 6.39), having fitted stair gates (OR 1.61, 95% CI 1.19 to 2.17), and
      having socket covers on unused sockets (OR 2.69, 95% CI 1.46 to
      4.96).Interventions providing free, low cost or discounted safety equipment
      appeared to be more effective in improving some safety practices than those
      interventions not doing so. There was no consistent evidence that interventions
      were less effective in families whose children were at greater risk of injury.
      AUTHORS' CONCLUSIONS: Home safety interventions most commonly provided as one-to
      one, face-to-face education, especially with the provision of safety equipment,
      are effective in increasing a range of safety practices. There is some evidence
      that such interventions may reduce injury rates, particularly where interventions
      are provided at home. Conflicting findings regarding interventions providing
      safety equipment on safety practices and injury outcomes are likely to be
      explained by two large studies; one clinic-based study provided equipment but did
      not reduce injury rates and one school-based study did not provide equipment but
      did demonstrate a significant reduction in injury rates. There was no consistent
      evidence that home safety education, with or without the provision of safety
      equipment, was less effective in those participants at greater risk of injury.
      Further studies are still required to confirm these findings with respect to
      injury rates.

PMID- 22972082
TI  - High-flux versus low-flux membranes for end-stage kidney disease.
AB  - BACKGROUND: Clinical practice guidelines regarding the use of high-flux
      haemodialysis membranes vary widely. OBJECTIVES: We aimed to analyse the current
      evidence reported for the benefits and harms of high-flux and low-flux
      haemodialysis. SEARCH METHODS: We searched Cochrane Renal Group's specialised
      register (July 2012), the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE (1948 to March 2011), and EMBASE (1947 to March 2011) without
      language restriction. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) that compared high-flux haemodialysis with low-flux haemodialysis
      in people with end-stage kidney disease (ESKD) who required long-term
      haemodialysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by
      two authors for study characteristics (participants and interventions), risks of
      bias, and outcomes (all-cause mortality and cause-specific mortality,
      hospitalisation, health-related quality of life, carpal tunnel syndrome, dialysis
      related arthropathy, kidney function, and symptoms) among people on
      haemodialysis. Treatment effects were expressed as a risk ratio (RR) or mean
      difference (MD), with 95% confidence intervals (CI) using the random-effects
      model. MAIN RESULTS: We included 33 studies that involved 3820 participants with
      ESKD. High-flux membranes reduced cardiovascular mortality (5 studies, 2612
      participants: RR 0.83, 95% CI 0.70 to 0.99) but not all-cause mortality (10
      studies, 2915 participants: RR 0.95, 95% CI 0.87 to 1.04) or infection-related
      mortality (3 studies, 2547 participants: RR 0.91, 95% CI 0.71 to 1.14). In
      absolute terms, high-flux membranes may prevent three cardiovascular deaths in
      100 people treated with haemodialysis for two years. While high-flux membranes
      reduced predialysis beta-2 microglobulin levels (MD -12.17 mg/L, 95% CI -15.83 to
      -8.51 mg/L), insufficient data were available to reliably estimate the effects of
      membrane flux on hospitalisation, carpal tunnel syndrome, or amyloid-related
      arthropathy. Evidence for effects of high-flux membranes was limited by selective
      reporting in a few studies. Insufficient numbers of studies limited our ability
      to conduct subgroup analyses for membrane type, biocompatibility, or reuse. In
      general, the risk of bias was either high or unclear in the majority of studies.
      AUTHORS' CONCLUSIONS: High-flux haemodialysis may reduce cardiovascular mortality
      in people requiring haemodialysis by about 15%. A large well-designed RCT is now
      required to confirm this finding.

PMID- 22972083
TI  - Terlipressin for hepatorenal syndrome.
AB  - BACKGROUND: Clinical trials suggest that terlipressin improves renal function in
      hepatorenal syndrome, but the evidence concerning mortality is equivocal.
      OBJECTIVES: To assess the beneficial and harmful effects of terlipressin alone or
      with albumin versus placebo, no intervention or albumin for hepatorenal syndrome.
      SEARCH METHODS: Eligible trials were identified through electronic (The Cochrane
      Library, MEDLINE, EMBASE and Science Citation Index databases) and manual
      searches until January 2012. SELECTION CRITERIA: Randomised clinical trials
      involving patients with type 1 or type 2 hepatorenal syndrome were included
      irrespective of publication status or language. DATA COLLECTION AND ANALYSIS: The
      review authors independently extracted data from trial reports and undertook
      correspondence with the authors. Primary outcome measures included mortality,
      reversal of hepatorenal syndrome and adverse events. Intention-to-treat, random
      effects model meta-analyses were performed and results were expressed as risk
      ratios (RR) with 95% confidence intervals (CI), and the I(2) statistic provided a
      measure of intertrial heterogeneity. Subgroup, sensitivity, regression and
      sequential analyses were performed. MAIN RESULTS: We identified six randomised
      clinical trials. All had high risk of bias. Five trials assessed terlipressin
      (with albumin in three trials) versus no intervention (with albumin in three
      trials) and one trial assessed terlipressin versus albumin. Data from five
      randomised trials on terlipressin alone (one trial) or terlipressin and albumin
      (four trials) were included in the review. In total, 74 of 155 (47.7%) patients
      randomised to terlipressin alone or terlipressin with albumin versus 98 of 154
      (63.6%) patients randomised to no intervention, placebo or albumin died. Random
      effects model meta-analysis found that terlipressin reduced mortality (RR 0.76,
      95% CI 0.61 to 0.95). The results were stable when repeated with trials on
      terlipressin plus albumin, trials on patients with type 2 hepatorenal syndrome,
      and trials with a low risk of selection bias. No evidence of bias or small study
      effects were identified in regression analyses. In a trial sequential analysis on
      mortality, the cumulative Z curve approached but did not cross the monitoring
      boundary suggesting that the results were not stable to adjustment for sparse
      data and multiple comparisons. Analyses of the remaining outcome measures found
      that terlipressin and albumin increased the number of patients with reversal of
      hepatorenal syndrome as well as adverse events, including cardiovascular and
      gastrointestinal symptoms. AUTHORS' CONCLUSIONS: Terlipressin may reduce
      mortality and improve renal function in patients with type 1 hepatorenal
      syndrome. Whether the evidence is strong enough to support the intervention for
      clinical practice could be debated due to the results of the trial sequential
      analyses. However, the outcome measures assessed are objective, which reduces the
      risk of bias.

PMID- 22972084
TI  - Restriction of oral intake of water for aspiration lung disease in children.
AB  - BACKGROUND: Primary aspiration of food and fluid is commonly seen in children
      with feeding and swallowing difficulties associated with a range of diseases and
      complex medical conditions. Respiratory sequelae and pneumonia are known to be
      associated with primary aspiration of ingested material, however causality
      between primary aspiration of specific food and fluid types and pulmonary effects
      in children is yet to be established in controlled trials. The relative pulmonary
      morbidity of aspiration of ingested food and fluid materials versus other causes
      of respiratory disease such as viral and bacterial causes, secondary aspiration
      of gastrointestinal contents and predisposing lung conditions such as chronic
      neonatal lung disease in a developing immune system is also unclear. Current
      management decisions for children who aspirate have to optimise oral nutrition
      and hydration, while reducing the risk of aspiration to preserve pulmonary
      integrity. This generally includes restricting aspirated food or fluids and
      providing texture-modified diets and thickened fluids. Young children frequently
      refuse thickened fluids providing a management dilemma for both families and
      health professionals. OBJECTIVES: Our objective was to evaluate the efficacy of
      restriction of oral water ingestion on the pulmonary status of children with thin
      fluid aspiration demonstrated on a modified barium swallow study. SEARCH METHODS:
      The Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane
      Airways Collaborative Review Group Specialised Register, MEDLINE, EMBASE and
      CINAHL databases were searched by the Cochrane Airways Group. The latest search
      was performed in May 2102. SELECTION CRITERIA: All randomised controlled trials
      comparing restriction of oral intake of water with unlimited oral water ingestion
      were eligible to be included. DATA COLLECTION AND ANALYSIS: Results of searches
      were reviewed against a pre-determined criteria for inclusion. No eligible trials
      were identified for a paediatric population and thus no data were available for
      analysis. One trial in an adult population was identified and reported. MAIN
      RESULTS: No randomised controlled trials examining the efficacy of restriction of
      oral intake of water in the management of children with thin fluid aspiration
      were found. In a single study in an adult population with stroke, no significant
      differences were seen between a control group of oral water restriction and the
      experimental group of unlimited oral water ingestion on outcomes such as
      pneumonia, total oral fluid intake and dehydration. AUTHORS' CONCLUSIONS: There
      are no trials that have adequately evaluated the pulmonary effects of allowing or
      restricting oral water ingestion in children known to have primary aspiration of
      thin fluids. Thus, there is currently an absence of evidence to support a strict
      approach of full restriction of oral intake of water or support a more liberal
      approach of allowing oral water ingestion in children with primary aspiration of
      thin fluids.

PMID- 22972085
TI  - Systemic interventions for recurrent aphthous stomatitis (mouth ulcers).
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most frequent form of oral
      ulceration, characterised by recurrent oral mucosal ulceration in an otherwise
      healthy individual. At its worst RAS can cause significant difficulties in eating
      and drinking. Treatment is primarily aimed at pain relief and the promotion of
      healing to reduce the duration of the disease or reduce the rate of recurrence. A
      variety of topical and systemic therapies have been utilised. OBJECTIVES: To
      determine the clinical effect of systemic interventions in the reduction of pain
      associated with RAS, a reduction in episode duration or frequency. SEARCH
      METHODS: We undertook electronic searches of: Cochrane Oral Health Group and
      PaPaS Trials Registers (to 6 June 2012); CENTRAL via The Cochrane Library (to
      Issue 4, 2012); MEDLINE via OVID (1950 to 6 June 2012); EMBASE via OVID (1980 to
      6 June 2012); CINAHL via EBSCO (1980 to 6 June 2012); and AMED via PubMed (1950
      to 6 June 2012). We searched reference lists from relevant articles and contacted
      the authors of eligible trials to identify further trials and obtain additional
      information. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      in which the primary outcome measures assess a reduction of pain associated with
      RAS, a reduction in episode duration or a reduction in episode frequency. Trials
      were not restricted by outcome alone. We also included RCTs of a cross-over
      design. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      data in duplicate. We contacted trial authors for details of randomisation,
      blindness and withdrawals. We carried out risk of bias assessment on six domains.
      We followed The Cochrane Collaboration statistical guidelines and risk ratio (RR)
      values were to be calculated using fixed-effect models (if two or three trials in
      each meta-analysis) or random-effects models (if four or more trials in each meta
      analysis). MAIN RESULTS: A total of 25 trials were included, 22 of which were
      placebo controlled and eight made head-to-head comparisons (five trials had more
      than two treatment arms). Twenty-one different interventions were assessed. The
      interventions were grouped into two categories: immunomodulatory/anti
      inflammatory and uncertain. Only one study was assessed as being at low risk of
      bias. There was insufficient evidence to support or refute the use of any
      intervention. AUTHORS' CONCLUSIONS: No single treatment was found to be effective
      and therefore the results remain inconclusive in regard to the best systemic
      intervention for RAS. This is likely to reflect the poor methodological rigour of
      trials, and lack of studies for certain drugs, rather than the true effect of the
      intervention. It is also recognised that in clinical practice, individual drugs
      appear to work for individual patients and so the interventions are likely to be
      complex in nature. In addition, it is acknowledged that systemic interventions
      are often reserved for those patients who have been unresponsive to topical
      treatments, and therefore may represent a select group of patients.

PMID- 22972087
TI  - Acupuncture for insomnia.
AB  - BACKGROUND: Although conventional non-pharmacological and pharmacological
      treatments for insomnia are effective in many people, alternative therapies such
      as acupuncture are widely practised. However, it remains unclear whether current
      evidence is rigorous enough to support acupuncture for the treatment of insomnia.
      OBJECTIVES: To determine the efficacy and safety of acupuncture for insomnia.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts International,
      CINAHL, AMED, the Traditional Chinese Medical Literature Analysis and Retrieval
      System (TCMLARS), the World Health Organization (WHO) Trials Portal (ICTRP) and
      relevant specialised registers of the Cochrane Collaboration in October 2011. We
      screened reference lists of all eligible reports and contacted trial authors and
      experts in the field. SELECTION CRITERIA: Randomised controlled trials evaluating
      any form of acupuncture for insomnia. They compared acupuncture with/without
      additional treatment against placebo or sham or no treatment or same additional
      treatment. We excluded trials that compared different acupuncture methods or
      acupuncture against other treatments. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data and assessed risk of bias. We used odds
      ratio (OR) and mean difference for binary and continuous outcomes respectively.
      We combined data in meta-analyses where appropriate. MAIN RESULTS: Thirty-three
      trials were included. They recruited 2293 participants with insomnia, aged 15 to
      98 years, some with medical conditions contributing to insomnia (stroke, end
      stage renal disease, perimenopause, pregnancy, psychiatric diseases). They
      evaluated needle acupuncture, electroacupuncture, acupressure or magnetic
      acupressure.Compared with no treatment (two studies, 280 participants) or
      sham/placebo (two studies, 112 participants), acupressure resulted in more people
      with improvement in sleep quality (compared to no treatment: OR 13.08, 95%
      confidence interval (CI) 1.79 to 95.59; compared to sham/placebo: OR 6.62, 95% CI
      1.78 to 24.55). However, when assuming that dropouts had a worse outcome in
      sensitivity analysis the beneficial effect of acupuncture was inconclusive.
      Compared with other treatment alone, acupuncture as an adjunct to other treatment
      might marginally increase the proportion of people with improved sleep quality
      (13 studies, 883 participants, OR 3.08, 95% CI 1.93 to 4.90). On subgroup
      analysis, only needle acupuncture but not electroacupuncture showed benefits. All
      trials had high risk of bias and were heterogeneous in the definition of
      insomnia, participant characteristics, acupoints and treatment regimen. The
      effect sizes were generally small with wide confidence intervals. Publication
      bias was likely present. Adverse effects were rarely reported and they were
      minor. AUTHORS' CONCLUSIONS: Due to poor methodological quality, high levels of
      heterogeneity and publication bias, the current evidence is not sufficiently
      rigorous to support or refute acupuncture for treating insomnia. Larger high
      quality clinical trials are required.

PMID- 22972086
TI  - Pre-operative biliary drainage for obstructive jaundice.
AB  - BACKGROUND: Patients with obstructive jaundice have various pathophysiological
      changes that affect the liver, kidney, heart, and the immune system. There is
      considerable controversy as to whether temporary relief of biliary obstruction
      prior to major definitive surgery (pre-operative biliary drainage) is of any
      benefit to the patient. OBJECTIVES: To assess the benefits and harms of pre
      operative biliary drainage versus no pre-operative biliary drainage (direct
      surgery) in patients with obstructive jaundice (irrespective of a benign or
      malignant cause). SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group
      Controlled Trials Register, Cochrane Central Register of Controlled Clinical
      Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation
      Index Expanded until February 2012. SELECTION CRITERIA: We included all
      randomised clinical trials comparing biliary drainage followed by surgery versus
      direct surgery, performed for obstructive jaundice, irrespective of the sample
      size, language, and publication status. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trials for inclusion and extracted data. We calculated the
      risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence
      intervals (CI) based on the available patient analyses. We assessed the risk of
      bias (systematic overestimation of benefit or systematic underestimation of harm)
      with components of the Cochrane risk of bias tool. We assessed the risk of play
      of chance (random errors) with trial sequential analysis. MAIN RESULTS: We
      included six trials with 520 patients comparing pre-operative biliary drainage
      (265 patients) versus no pre-operative biliary drainage (255 patients). Four
      trials used percutaneous transhepatic biliary drainage and two trials used
      endoscopic sphincterotomy and stenting as the method of pre-operative biliary
      drainage. The risk of bias was high in all trials. The proportion of patients
      with malignant obstruction varied between 60% and 100%. There was no significant
      difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative
      biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12;
      95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the
      pre-operative biliary drainage group (60 per 100 patients in the pre-operative
      biliary drainage group versus 26 per 100 patients in the direct surgery group)
      (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who
      developed serious morbidity was significantly higher in the pre-operative biliary
      drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus
      the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not
      reported in any of the trials. There was no significant difference in the length
      of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI -1.28 to 11.02; P
      = 0.12) between the two groups. Trial sequential analysis showed that for
      mortality only a small proportion of the required information size had been
      obtained. There seemed to be no significant differences in the subgroup of trials
      assessing percutaneous compared to endoscopic drainage. AUTHORS' CONCLUSIONS:
      There is currently not sufficient evidence to support or refute routine pre
      operative biliary drainage for patients with obstructive jaundice. Pre-operative
      biliary drainage may increase the rate of serious adverse events. So, the safety
      of routine pre-operative biliary drainage has not been established. Pre-operative
      biliary drainage should not be used in patients undergoing surgery for
      obstructive jaundice outside randomised clinical trials.

PMID- 22972088
TI  - Treatments for suppression of lactation.
AB  - BACKGROUND: Various pharmacologic and non-pharmacologic interventions have been
      used to suppress lactation after childbirth and relieve associated symptoms.
      Despite the large volume of literature on the subject, there is currently no
      universal guideline on the most appropriate approach for suppressing lactation in
      postpartum women. OBJECTIVES: To evaluate the effectiveness and safety of
      interventions used for suppression of lactation in postpartum women (who have not
      breastfed or expressed breastmilk) to determine which approach has the greatest
      comparative benefits with least risk. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 June 2012). SELECTION
      CRITERIA: Randomised trials evaluating the effectiveness of treatments used for
      suppression of postpartum lactation. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial quality and extracted data. MAIN RESULTS: We
      included 62 trials (6428 women). Twenty-two trials did not contribute data to the
      meta-analyses. The trials were generally small and of limited quality. Three
      trials (107 women) indicated that bromocriptine significantly reduced the
      proportion of women lactating compared with no treatment at or within seven days
      postpartum (three trials, 107 women; risk ratio (RR) 0.36, 95% confidence
      interval (CI) 0.24 to 0.54). Seven trials involving oestrogen preparations
      (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol) suggested that they
      significantly reduced the proportion of lactating women compared with no
      treatment at or within seven days postpartum (RR 0.40, 95% CI 0.29 to 0.56). We
      found no trials comparing non-pharmacologic methods with no treatment. Trials
      comparing bromocriptine with other pharmacologic agents such as methergoline,
      prostaglandins, pyridoxine, carbegoline, diethylstilbestrol and cyclofenil
      suggested similarity in their effectiveness. Side effects were poorly reported in
      the trials and no case of thromboembolism was recorded in the four trials that
      reported it as an outcome. AUTHORS' CONCLUSIONS: There is weak evidence that some
      pharmacologic treatments (most of which are currently unavailable to the public)
      are better than no treatment for suppressing lactation symptoms in the first
      postpartum week. No evidence currently exists to indicate whether non
      pharmacologic approaches are more effective than no treatment. Presently, there
      is insufficient evidence to address the side effects of methods employed for
      suppressing lactation. When women desire treatment, bromocriptine may be
      considered where it is registered for lactation suppression in those without
      predisposition to its major side effects of public concerns. Many trials did not
      contribute data that could be included in analyses. Large randomised trials are
      needed to compare the effectiveness of pharmacologic (especially bromocriptine)
      and non-pharmacologic methods with no treatment. Such trials should consider the
      acceptability of the intervention and lactation symptoms of concern to women and
      be large enough to detect clinically important differences in major side effects
      between comparison groups.

PMID- 22972089
TI  - Antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with
      acute or chronic liver disease.
AB  - BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of
      morbidity and mortality in the course of liver cirrhosis. Patients with liver
      disease frequently have haemostatic abnormalities like hyperfibrinolysis.
      Therefore, antifibrinolytic amino acids have been proposed to be used as
      supplementary interventions alongside any of the primary treatments for upper
      gastrointestinal bleeding in patients with liver diseases. OBJECTIVES: To assess
      the beneficial and harmful effects of antifibrinolytic amino acids for upper
      gastrointestinal bleeding in patients with acute or chronic liver disease. SEARCH
      METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register
      (11 June 2012), Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library (2012, Issue 5 of 12), MEDLINE (Ovid SP) (1946 to June 2012),
      EMBASE (Ovid SP) (1974 to June 2012), Science Citation Index EXPANDED (1900 to
      June 2012), LILACS (1982 to June 2012), Clinical Trials Search Portal of the WHO
      (accessed June 18, 2012), and the Metaregister of Controlled Trials (accessed
      June 18, 2012). We scrutinised the reference lists of the retrieved publications.
      SELECTION CRITERIA: Randomised clinical trials irrespective of blinding,
      language, or publication status for assessment of benefits and harms.
      Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: Data
      from randomised clinical trials were to be summarised by standard Cochrane
      Collaboration methodologies. MAIN RESULTS: We could not find any randomised
      clinical trials assessing antifibrinolytic amino acids for treating upper
      gastrointestinal bleeding in patients with acute or chronic liver disease. We
      could not identify quasi-randomised, historically controlled, or observational
      studies in which we could assess harms. AUTHORS' CONCLUSIONS: No randomised
      clinical trials assessing the benefits and harms of antifibrinolytic amino acids
      for upper gastrointestinal bleeding in patients with acute or chronic liver
      disease were identified. The benefits and harms of antifibrinolytic amino acids
      need to be tested in randomised clinical trials. Unless randomised clinical
      trials are conducted to assess the trade off between benefits and harms, we
      cannot recommend nor refute antifibrinolytic amino acids for upper
      gastrointestinal bleeding in patients with acute or chronic liver diseases.

PMID- 22972090
TI  - Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the
      treatment of brain metastases.
AB  - BACKGROUND: Historically, whole brain radiation therapy (WBRT) has been the main
      treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high
      dose focused radiation and is being increasingly utilized to treat brain
      metastases. The benefit of adding SRS to WBRT is unclear. This is an updated
      version of the original Cochrane review published in Issue 6, 2010. OBJECTIVES:
      To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of
      brain metastases. SEARCH METHODS: In the original review we searched the
      following electronic databases: Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and
      CancerLit (1975 to 2009) in order to identify trials for inclusion in this
      review.In this update we searched the following electronic databases in May 2012:
      Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2012), MEDLINE
      (2009 to May week 4 2012), and EMBASE (2009 to 2012 week 21) in order to identify
      trials for inclusion in the review. SELECTION CRITERIA: The review was restricted
      to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus
      WBRT alone for upfront treatment of adult patients with newly diagnosed
      metastases (single or multiple) in the brain resulting from any primary,
      extracranial cancer. DATA COLLECTION AND ANALYSIS: The Generic Inverse Variance
      method, random-effects model in RevMan 5 was used for the meta-analysis. MAIN
      RESULTS: A meta-analysis of two trials with a total of 358 participants, found no
      statistically significant difference in overall survival (OS) between WBRT plus
      SRS and WBRT alone groups (hazard ratio (HR) 0.82; 95% confidence interval (CI)
      0.65 to 1.02). For patients with one brain metastasis median survival was
      significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9
      months; P = 0.04). Patients in the WBRT plus SRS group had decreased local
      failure compared to patients who received WBRT alone (HR 0.27; 95% CI 0.14 to
      0.52). Furthermore, a statistically significant improvement in performance status
      scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged
      or improved Karnofsky Performance Scale (KPS) at 6 months was seen in 43% of
      patients in the combined therapy group versus only 28% in WBRT group (P = 0.03).
      Overall, risk of bias in the included studies was unclear. AUTHORS' CONCLUSIONS:
      Since the last version of this review no new studies were found that met the
      inclusion criteria. Given the unclear risk of bias in the included studies, the
      results of this analysis have to be interpreted with caution. Analysis of all
      included patients, SRS plus WBRT, did not show a survival benefit over WBRT
      alone. However, performance status and local control were significantly better in
      the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the
      combined treatment group for recursive partitioning analysis (RPA) Class I
      patients as well as patients with single metastasis.

PMID- 22972091
TI  - Low bacterial diet versus control diet to prevent infection in cancer patients
      treated with chemotherapy causing episodes of neutropenia.
AB  - BACKGROUND: Neutropenia is a potentially serious side effect of chemotherapy and
      a major risk factor for infections, which can be life-threatening. It has been
      hypothesised that a low bacterial diet (LBD) can prevent the occurrence of
      infections and (infection-related) mortality in cancer patients receiving
      chemotherapy causing episodes of neutropenia, but much remains unclear.
      OBJECTIVES: The primary objective was to determine the efficacy of an LBD versus
      a control diet in preventing the occurrence of infection and to decrease
      (infection-related) mortality in adult and paediatric cancer patients receiving
      chemotherapy causing episodes of neutropenia. Secondary objectives were to assess
      the time to first febrile episode, the need for empirical antibiotic therapy,
      diet acceptability and quality of life. SEARCH METHODS: We searched the following
      electronic databases: the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, issue 3 2011), Database of Abstracts of Reviews
      of Effects (DARE) (The Cochrane Library, issue 3 2011), PubMed (from 1946 to 20
      October 2011), EMBASE (from 1980 to 20 October 2011) and CINAHL (from 1981 to 20
      October 2011). In addition, we searched several conference proceedings (from 2000
      to either 2010 or 2011) and reference lists of relevant articles. To identify
      ongoing trials we contacted researchers working on this topic and we scanned the
      National Institute of Health Register and the ISRCTN Register (www.controlled
      trials.com; searched May 2012). SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing the use of an LBD with a control diet with regard to infection
      rate, (infection-related) mortality, time to first febrile episode, need for
      empirical antibiotic therapy, diet acceptability, and quality of life in adult
      and paediatric cancer patients receiving chemotherapy causing episodes of
      neutropenia. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed the study selection, 'Risk of bias' assessment and data extraction.
      Analyses were performed according to the guidelines of the Cochrane Handbook for
      Systematic Reviews of Interventions. MAIN RESULTS: We identified three RCTs
      assessing different intervention and control diets in 192 patients (97 randomised
      to intervention diet; 95 to control diet) with different types of malignancies.
      Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central
      venous catheter care, oral care, hygiene practices and colony-stimulating
      factors) and outcome definitions also differed between studies. In all included
      studies it was standard policy to give empirical antibiotics (and sometimes also
      antimycotics) to (some of) the patients diagnosed with an infection. Two studies
      included adults and one study included children. In all studies only a scant
      description of treatment regimens was provided. All studies had methodological
      limitations. Pooling of results of included studies was not possible. In two
      individual studies no statistically significant difference in infection rate
      between the intervention and control diet was identified; another study showed no
      significant difference in the number of chemotherapy cycles with an infection
      between the treatment groups. None of the studies mentioned infection-related
      mortality, but in one study no significant difference in overall survival between
      the treatment groups was observed. Time from onset of neutropenia to fever, the
      duration of empirical antibiotics and antimycotics, diet acceptability (i.e.
      following the diet easily and following the diet throughout all chemotherapy
      cycles) and quality of life were all evaluated by only one study; for all
      outcomes no statistically significant differences between the treatment arms was
      observed. AUTHORS' CONCLUSIONS: At the moment there is no evidence from
      individual RCTs in children and adults with different malignancies that
      underscores the use of an LBD for the prevention of infection and related
      outcomes. All studies differed with regard to co-interventions, outcome
      definitions, and intervention and control diets. Since pooling of results was not
      possible and all studies had serious methodological limitations, no definitive
      conclusions can be made. It should be noted that 'no evidence of effect', as
      identified in this review, is not the same as 'evidence of no effect'. Based on
      the currently available evidence, we are not able to give recommendations for
      clinical practice. More high-quality research is needed.

PMID- 22972092
TI  - Antenatal breastfeeding education for increasing breastfeeding duration.
AB  - BACKGROUND: Breastfeeding (BF) is well recognised as the best food for infants.
      The impact of antenatal BF education on the duration of BF has not been
      evaluated. OBJECTIVES: To evaluate the effectiveness of antenatal BF education
      for increasing BF initiation and duration. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (2 December 2011),
      CENTRAL (The Cochrane Library 2011, Issue 11), MEDLINE (1966 to 30 November 2011)
      and Scopus (January 1985 to 30 November 2011). We contacted experts and searched
      reference lists of retrieved articles. SELECTION CRITERIA: All identified
      published, unpublished and ongoing randomised controlled trials (RCTs) assessing
      the effect of formal antenatal BF education or comparing two different methods of
      formal antenatal BF education, on duration of BF. We excluded RCTs that also
      included intrapartum or postpartum BF education. DATA COLLECTION AND ANALYSIS: We
      assessed all potential studies identified as a result of the search strategy. Two
      review authors extracted data from each included study using the agreed form and
      assessed risk of bias. We resolved discrepancies through discussion. MAIN
      RESULTS: We included 19 studies with 8506 women in the review and 16 studies
      involving 8262 women contributed data to the analyses. We did not carry out any
      meta-analysis because there was only one study for each comparison.Five studies
      compared a single method of BF education with routine care. Peer counselling
      significantly increased BF initiation.Three studies compared one form of BF
      education versus another. No intervention was significantly more effective than
      another intervention in increasing initiation or duration of BF.Seven studies
      compared multiple methods versus a single method of BF education. Combined BF
      educational interventions were not significantly better than a single
      intervention in initiating or increasing BF duration. However, in one trial a
      combined BF education significantly reduced nipple pain and trauma.One study
      compared different combinations of interventions. There was a marginally
      significant increase in exclusive BF at six months in women receiving a booklet
      plus video plus lactation consultation (LC) compared with the booklet plus video
      only.Two studies compared multiple methods of BF education versus routine care.
      The combination of BF booklet plus video plus LC was significantly better than
      routine care for exclusive BF at three months. AUTHORS' CONCLUSIONS: Because
      there were significant methodological limitations and the observed effect sizes
      were small, it is not appropriate to recommend any specific antenatal BF
      education.There is an urgent need to conduct RCTs with adequate power to evaluate
      the effectiveness of antenatal BF education.

PMID- 22972093
TI  - Robot assistant versus human or another robot assistant in patients undergoing
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The role of a robotic assistant in laparoscopic cholecystectomy is
      controversial. While some trials have shown distinct advantages of a robotic
      assistant over a human assistant others have not, and it is unclear which robotic
      assistant is best. OBJECTIVES: The aims of this review are to assess the benefits
      and harms of a robot assistant versus human assistant or versus another robot
      assistant in laparoscopic cholecystectomy, and to assess whether the robot can
      substitute the human assistant. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE,
      and Science Citation Index Expanded (until February 2012) for identifying the
      randomised clinical trials. SELECTION CRITERIA: Only randomised clinical trials
      (irrespective of language, blinding, or publication status) comparing robot
      assistants versus human assistants in laparoscopic cholecystectomy were
      considered for the review. Randomised clinical trials comparing different types
      of robot assistants were also considered for the review. DATA COLLECTION AND
      ANALYSIS: Two authors independently identified the trials for inclusion and
      independently extracted the data. We calculated the risk ratio (RR) or mean
      difference (MD) with 95% confidence interval (CI) using the fixed-effect and the
      random-effects models based on intention-to-treat analysis, when possible, using
      Review Manager 5. MAIN RESULTS: We included six trials with 560 patients. One
      trial involving 129 patients did not state the number of patients randomised to
      the two groups. In the remaining five trials 431 patients were randomised, 212 to
      the robot assistant group and 219 to the human assistant group. All the trials
      were at high risk of bias. Mortality and morbidity were reported in only one
      trial with 40 patients. There was no mortality or morbidity in either group.
      Mortality and morbidity were not reported in the remaining trials. Quality of
      life or the proportion of patients who were discharged as day-patient
      laparoscopic cholecystectomy patients were not reported in any trial. There was
      no significant difference in the proportion of patients who required conversion
      to open cholecystectomy (2 trials; 4/63 (weighted proportion 6.4%) in the robot
      assistant group versus 5/70 (7.1%) in the human assistant group; RR 0.90; 95% CI
      0.25 to 3.20). There was no significant difference in the operating time between
      the two groups (4 trials; 324 patients; MD 5.00 minutes; 95% CI -0.55 to 10.54).
      In one trial, about one sixth of the laparoscopic cholecystectomies in which a
      robot assistant was used required temporary use of a human assistant. In another
      trial, there was no requirement for human assistants. One trial did not report
      this information. It appears that there was little or no requirement for human
      assistants in the other three trials. There were no randomised trials comparing
      one type of robot versus another type of robot. AUTHORS' CONCLUSIONS: Robot
      assisted laparoscopic cholecystectomy does not seem to offer any significant
      advantages over human assisted laparoscopic cholecystectomy. However, all trials
      had a high risk of systematic errors or bias (that is, risk of overestimation of
      benefit and underestimation of harm). All trials were small, with few or no
      outcomes. Hence, the risk of random errors (that is, play of chance) is high.
      Further randomised trials with low risk of bias or random errors are needed.

PMID- 22972094
TI  - N-acetylcysteine for sepsis and systemic inflammatory response in adults.
AB  - BACKGROUND: Death is common in systemic inflammatory response syndrome (SIRS) or
      sepsis-induced multisystem organ failure and it has been thought that
      antioxidants such as N-acetylcysteine could be beneficial. OBJECTIVES: We
      assessed the clinical effectiveness of intravenous N-acetylcysteine for the
      treatment of patients with SIRS or sepsis. SEARCH METHODS: We searched the
      following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The
      Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE
      (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts
      Clinical Trials Register and Current Controlled Trials (www.controlled
      trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of
      Knowledge and the National Trials Register to identify all relevant randomized
      controlled trials available for review. SELECTION CRITERIA: We included only
      randomized controlled trials (RCTs) in the meta-analysis. DATA COLLECTION AND
      ANALYSIS: We independently performed study selection, quality assessment and data
      extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured
      statistical heterogeneity using the I(2) statistic. MAIN RESULTS: We included 41
      fully published studies (2768 patients). Mortality was similar in the N
      acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) =
      0%). Neither did N-acetylcysteine show any significant effect on length of stay,
      duration of mechanical ventilation or incidence of new organ failure. Early
      application of N-acetylcysteine to prevent the development of an oxidato
      inflammatory response did not affect the outcome, nor did late application that
      is after 24 hours of developing symptoms. Late application was associated with
      cardiovascular instability. AUTHORS' CONCLUSIONS: Overall, this meta-analysis
      puts doubt on the safety and utility of intravenous N-acetylcysteine as an
      adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in
      reducing mortality and complications in this patient population. At worst, it can
      be harmful, especially when administered later than 24 hours after the onset of
      symptoms, by causing cardiovascular depression. Unless future RCTs provide
      evidence of treatment effect, clinicians should not routinely use intravenous N
      acetylcysteine in SIRS or sepsis and academics should not promote its use.

PMID- 22972095
TI  - Separate care for new mother and infant versus rooming-in for increasing the
      duration of breastfeeding.
AB  - BACKGROUND: Separate care for a new mother and infant may affect the duration of
      breastfeeding, breastfeeding behaviour and may have an adverse effect on neonatal
      and maternal outcomes. OBJECTIVES: To assess the effect of mother-infant
      separation versus rooming-in on the duration of breastfeeding (exclusive and
      total duration of breastfeeding). SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (30 June 2012). SELECTION
      CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) investigating
      the effect of separate mother-infant care versus rooming-in after hospital birth
      or at home on the duration of breastfeeding, proportion of breastfeeding at six
      months and adverse neonatal and maternal outcomes. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed the studies for inclusion and assessed
      trial quality. Two review authors extracted data. Data were checked for accuracy.
      MAIN RESULTS: There were 23 reports from 19 potential trials identified. After
      assessment, one trial (involving 176 women) met our inclusion criteria.One trial
      reported an overall median duration of any breastfeeding of four months.
      Exclusive breastfeeding before discharge from hospital (at day four postpartum)
      was significantly lower in the separate care group compared with the rooming-in
      group (risk ratio (RR) 0.58; 95% CI 0.42 to 0.81; one trial, 141 women). 
      AUTHORS' CONCLUSIONS: We found little evidence to support or refute the practice
      of mother-infant separation versus rooming-in. Therefore, we see no reason to
      practise it. We recommend a well designed RCT to investigate full mother-infant
      rooming-in versus partial rooming-in or separate care on all of the primary and
      secondary outcomes suggested.

PMID- 22972096
TI  - Laparoscopy versus laparotomy for the management of early stage endometrial
      cancer.
AB  - BACKGROUND: Traditionally, surgery for endometrial cancer (hysterectomy with
      removal of both fallopian tubes and ovaries) is performed through laparotomy. It
      has been suggested that the laparoscopic approach is associated with a reduction
      in operative morbidity. Over the last 10 to 15 years there has been a steady
      increase of laparoscopy for endometrial cancer. This review investigates the
      evidence of benefits and harms of laparoscopic surgery compared with laparotomy
      for presumed early stage endometrial cancer. OBJECTIVES: To compare the overall
      survival (OS) and disease-free survival (DFS) for laparoscopic surgery versus
      laparotomy in women with presumed early stage endometrial cancer. SEARCH METHODS:
      We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane
      Central Register of Controlled Trials (CENTRAL) Issue 3, 2012, MEDLINE, EMBASE
      and CINAHL up to April 2012. We also searched registers of clinical trials,
      abstracts of scientific meetings, and reference lists of included studies. Trial
      registers we searched included NHMRC Clinical Trials Register, UKCCCR Register of
      Cancer Trials, Meta-Register and Physician Data Query Protocol, as well as
      abstracts of scientific meetings. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial
      cancer. DATA COLLECTION AND ANALYSIS: We independently abstracted data and
      assessed risk of bias. Hazard ratios (HRs) were used for OS and recurrence-free
      survival (RFS), risk ratios (RR) for severe adverse events and the mean
      difference (MD) method was used for continuous outcomes in women who received
      laparoscopy or laparotomy and these were then pooled in random-effects meta
      analyses. MAIN RESULTS: Eight RCTs comparing laparoscopy with laparotomy for the
      surgical management of early stage endometrial cancer were identified.All eight
      trials met the inclusion criteria, 3644 women were assessed at the end of the
      trials. Three trials assessing 359 participants with early stage endometrial
      cancer, found no statistically significant difference in the risk of death and
      disease or recurrence between women who underwent laparoscopy and those who
      underwent laparotomy (HR = 1.14, 95% confidence interval (CI): 0.62 to 2.10) and
      HR = 1.13, 95% CI: 0.90 to 1.42 for OS and RFS respectively). There was no
      statistically significant difference in the rate of peri-operative death, women
      requiring a blood transfusion, and bladder, ureteric, bowel and vascular injury.
      However, a meta-analysis of two trials found that women in the laparoscopy group
      lost significantly less blood than those in the laparotomy group (MD = -106.82
      mL, 95% CI: -141.59 to -72.06). A further meta-analysis of two trials, which
      assessed 2923 women and included one very large trial of over 2500 participants,
      found that the rate of severe post-operative adverse events was significantly
      lower in the laparoscopy group compared with the laparotomy group (RR = 0.58, 95%
      CI: 0.37 to 0.91). The large trial did not give a breakdown of these severe post
      operative adverse events into different adverse event categories. Most trials
      were at moderate risk of bias. Hospital stay was reported in all of the trials
      and results show that on average, laparoscopy was associated with a significantly
      shorter hospital stay. AUTHORS' CONCLUSIONS: This review has found evidence to
      support the role of laparoscopy for the management of early endometrial
      cancer.For presumed early stage primary endometrioid adenocarcinoma of the
      endometrium, laparoscopy is associated with similar overall and disease-free
      survival. Laparoscopy is associated with reduced operative morbidity and hospital
      stay. There is no significant difference in severe post-operative morbidity
      between the two modalities.

PMID- 22972097
TI  - Interventions for late trabeculectomy bleb leak.
AB  - BACKGROUND: Late trabeculectomy bleb leaks are a common complication after
      filtering glaucoma surgery. Although asymptomatic, late bleb leaks may lead to
      hypotony and are associated with bleb related infections. OBJECTIVES: To assess
      the effects of interventions for late trabeculectomy bleb leak. SEARCH METHODS:
      We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2012, Issue 7), MEDLINE (January 1946 to July
      2012), EMBASE (January 1980 to July 2012), the metaRegister of Controlled Trials
      (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov)
      and the WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 18 July 2012. SELECTION CRITERIA: We included randomised and quasi-randomised
      trials in which any treatments for eyes with late bleb leak (interventional and
      non-interventional) were compared with each other. DATA COLLECTION AND ANALYSIS:
      Two authors independently assessed trial quality and extracted data. We contacted
      study authors when additional information was needed. MAIN RESULTS: The review
      included one multicentre trial based in the USA with 30 eyes of 30 participants.
      The trial compared two surgical procedures (conjunctival advancement and amniotic
      membrane transplant) to cover a filtering bleb leak. Conjunctival advancement has
      been shown to be more effective in sealing filtering bleb leaks. AUTHORS'
      CONCLUSIONS: Although a variety of treatments have been proposed for bleb leaks,
      there is no evidence of their comparative effectiveness.The evidence in this
      review was provided by a single trial that compared two surgical procedures
      (conjunctival advancement and amniotic membrane transplant). The trial did show a
      superiority of conjunctival advancement, which was regarded as standard
      treatment, to amniotic membrane transplantation. There is a need for more
      randomised trials to validate the findings of this single trial and provide more
      information on the different types of interventions, especially non-surgical
      treatments compared to surgical procedures. We recommend that any intervention
      should be compared to a standard procedure, which is to date conjunctival
      advancement.

PMID- 22972098
TI  - Early amniotomy and early oxytocin for prevention of, or therapy for, delay in
      first stage spontaneous labour compared with routine care.
AB  - BACKGROUND: Caesarean section rates are over 20% in many developed countries. The
      main diagnosis contributing to the high rate in nulliparae is dystocia or
      prolonged labour. The present review assesses the effects of a policy of early
      amniotomy with early oxytocin administration for the prevention of, or the
      therapy for, delay in labour progress. OBJECTIVES: To estimate the effects of
      early augmentation with amniotomy and oxytocin for prevention of, or therapy for,
      delay in labour progress on the caesarean birth rate and on indicators of
      maternal and neonatal morbidity. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (15 February 2012), MEDLINE
      (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15
      February 2012), MIDIRS (1985 to February 2012) and contacted authors for data
      from unpublished trials. SELECTION CRITERIA: Randomized and quasi-randomized
      controlled trials that compared oxytocin and amniotomy with expectant management.
      DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently.
      We stratified the analyses into 'Prevention Trials' and 'Therapy Trials'
      according to the status of the woman at the time of randomization. Participants
      in the 'Prevention Trials' were unselected women, without slow progress in
      labour, who were randomized to a policy of early augmentation or to routine care.
      In 'Treatment Trials' women were eligible if they had an established delay in
      labour progress. MAIN RESULTS: For this update, we have included a further two
      new clinical trials. This updated review includes 14 trials, randomizing a total
      of 8033 women. The unstratified analysis found early intervention with amniotomy
      and oxytocin to be associated with a modest reduction in the risk of caesarean
      section; however, the confidence interval (CI) included the null effect (risk
      ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention
      trials, early augmentation was associated with a modest reduction in the number
      of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of
      early amniotomy and early oxytocin was associated with a shortened duration of
      labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight
      trials; 4816 women). Sensitivity analyses excluding four trials with a full
      package of active management did not substantially affect the point estimate for
      risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women).
      We found no other significant effects for the other indicators of maternal or
      neonatal morbidity. AUTHORS' CONCLUSIONS: In prevention trials, early
      intervention with amniotomy and oxytocin appears to be associated with a modest
      reduction in the rate of caesarean section over standard care.

PMID- 22972100
TI  - High initial concentration versus low initial concentration sevoflurane for
      inhalational induction of anaesthesia.
AB  - BACKGROUND: Sevoflurane induction for general anaesthesia has been reported to be
      safe, reliable and well accepted by patients. Sevoflurane induction uses either
      low or high initial concentrations. The low initial concentration technique
      involves initially administering a low concentration then gradually increasing
      the dose until the patient is anaesthetized. The high initial concentration
      technique involves administering high concentrations from the beginning,
      continuing until the patient is anaesthetized. OBJECTIVES: We aimed to compare
      the induction times and complications between high and low initial concentration
      sevoflurane induction in patients who received inhalational induction for general
      anaesthesia. We defined 'high' as greater and 'low' as less than a 4% initial
      concentration. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 9); MEDLINE (1950
      to September 2011); EMBASE (1980 to September 2011); LILACS (1982 to September
      2011) and ISI Web of Science (1946 to September 2011). We also searched the
      reference lists of relevant articles, conference proceedings; and contacted the
      authors of included trials. SELECTION CRITERIA: We sought all published and
      unpublished, randomized controlled trials comparing high versus low initial
      sevoflurane concentration inhalational induction. Our primary outcomes were two
      measures of anaesthesia (time to loss of the eyelash reflex (LOER) and time until
      a weighted object held in the patient's hand was dropped), time to successful
      insertion of a laryngeal mask airway (LMA), and time to endotracheal intubation.
      Other outcomes were complications of the technique. DATA COLLECTION AND ANALYSIS:
      We used the standardized methods for conducting a systematic review as described
      by the Cochrane Handbook for Systematic Reviews of Interventions. Two authors
      independently extracted details of trial methodology and outcome data from
      reports of all trials considered eligible for inclusion. All analyses were made
      on an intention-to-treat basis, where possible. The overall treatment effects
      were estimated by using a fixed-effect model when there was no substantial
      heterogeneity, whereas the random-effects model was applied in the presence of
      considerable heterogeneity. MAIN RESULTS: We used data from 10 studies with 729
      participants in the review, though most analyses were based on data from fewer
      participants. There was substantial heterogeneity in the trials. Thus, our
      results should be read with caution. It was not possible to combine the trials
      for the primary outcome (LOER) but individual trials found faster induction times
      (typically 24 to 82 seconds faster) with high initial concentration sevoflurane.
      Apnoea appeared to be more common in the high initial concentration sevoflurane
      group (two trials,160 participants). There was no evidence of a difference in the
      incidence of cough, laryngospasm, breath holding, bradycardia, salivation and
      hypotension between the two groups, with the overall incidence of complications
      being low. AUTHORS' CONCLUSIONS: A high initial concentration sevoflurane
      technique probably offers more rapid induction of anaesthesia and a similar rate
      of complications except for apnoea, which may be more common with a high initial
      concentration. However, this conclusion is not definitive.

PMID- 22972099
TI  - Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus
      long-acting beta(2)-agonists for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Both inhaled steroids (ICS) and long-acting beta(2)-agonists (LABA)
      are used in the management of chronic obstructive pulmonary disease (COPD). This
      updated review compared compound LABA plus ICS therapy (LABA/ICS) with the LABA
      component drug given alone. OBJECTIVES: To assess the efficacy of ICS and LABA in
      a single inhaler with mono-component LABA alone in adults with COPD. SEARCH
      METHODS: We searched the Cochrane Airways Group Specialised Register of trials.
      The date of the most recent search was November 2011. SELECTION CRITERIA: We
      included randomised, double-blind controlled trials. We included trials comparing
      compound ICS and LABA preparations with their component LABA preparations in
      people with COPD. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed study risk of bias and extracted data. The primary outcomes were
      exacerbations, mortality and pneumonia, while secondary outcomes were health
      related quality of life (measured by validated scales), lung function,
      withdrawals due to lack of efficacy, withdrawals due to adverse events and side
      effects. Dichotomous data were analysed as random-effects model odds ratios or
      rate ratios with 95% confidence intervals (CIs), and continuous data as mean
      differences and 95% CIs. We rated the quality of evidence for exacerbations,
      mortality and pneumonia according to recommendations made by the GRADE working
      group. MAIN RESULTS: Fourteen studies met the inclusion criteria, randomising
      11,794 people with severe COPD. We looked at any LABA plus ICS inhaler (LABA/ICS)
      versus the same LABA component alone, and then we looked at the 10 studies which
      assessed fluticasone plus salmeterol (FPS) and the four studies assessing
      budesonide plus formoterol (BDF) separately. The studies were well-designed with
      low risk of bias for randomisation and blinding but they had high rates of
      attrition, which reduced our confidence in the results for outcomes other than
      mortality.Primary outcomes There was low quality evidence that exacerbation rates
      in people using LABA/ICS inhalers were lower in comparison to those with LABA
      alone, from nine studies which randomised 9921 participants (rate ratio 0.76; 95%
      CI 0.68 to 0.84). This corresponds to one exacerbation per person per year on
      LABA and 0.76 exacerbations per person per year on ICS/LABA. Our confidence in
      this effect was limited by statistical heterogeneity between the results of the
      studies (I(2) = 68%) and a risk of bias from the high withdrawal rates across the
      studies. When analysed as the number of people experiencing one or more
      exacerbations over the course of the study, FPS lowered the odds of an
      exacerbation with an odds ratio (OR) of 0.83 (95% CI 0.70 to 0.98, 6 studies,
      3357 participants). With a risk of an exacerbation of 47% in the LABA group over
      one year, 42% of people treated with LABA/ICS would be expected to experience an
      exacerbation. Concerns over the effect of reporting biases led us to downgrade
      the quality of evidence for this effect from high to moderate.There was no
      significant difference in the rate of hospitalisations (rate ratio 0.79; 95% CI
      0.55 to 1.13, very low quality evidence due to risk of bias, statistical
      imprecision and inconsistency). There was no significant difference in mortality
      between people on combined inhalers and those on LABA, from 10 studies on 10,680
      participants (OR 0.92; 95% CI 0.76 to 1.11, downgraded to moderate quality
      evidence due to statistical imprecision). Pneumonia occurred more commonly in
      people randomised to combined inhalers, from 12 studies with 11,076 participants
      (OR 1.55; 95% CI 1.20 to 2.01, moderate quality evidence due to risk of bias in
      relation to attrition) with an annual risk of around 3% on LABA alone compared to
      4% on combination treatment. There were no significant differences between the
      results for either exacerbations or pneumonia from trials adding different doses
      or types of inhaled corticosteroid.Secondary outcomes ICS/LABA was more effective
      than LABA alone in improving health-related quality of life measured by the St
      George's Respiratory Questionnaire (1.58 units lower with FPS; 2.69 units lower
      with BDF), dyspnoea (0.09 units lower with FPS), symptoms (0.07 units lower with
      BDF), rescue medication (0.38 puffs per day fewer with FPS, 0.33 puffs per day
      fewer with BDF), and forced expiratory volume in one second (FEV(1)) (70 mL
      higher with FPS, 50 mL higher with BDF). Candidiasis (OR 3.75) and upper
      respiratory infection (OR 1.32) occurred more frequently with FPS than SAL. We
      did not combine adverse event data relating to candidiasis for BDF studies as the
      results were very inconsistent. AUTHORS' CONCLUSIONS: Concerns over the analysis
      and availability of data from the studies bring into question the superiority of
      ICS/LABA over LABA alone in preventing exacerbations. The effects on
      hospitalisations were inconsistent and require further exploration. There was
      moderate quality evidence of an increased risk of pneumonia with ICS/LABA. There
      was moderate quality evidence that treatments had similar effects on mortality.
      Quality of life, symptoms score, rescue medication use and FEV(1) improved more
      on ICS/LABA than on LABA, but the average differences were probably not
      clinically significant for these outcomes. To an individual patient the increased
      risk of pneumonia needs to be balanced against the possible reduction in
      exacerbations.More information would be useful on the relative benefits and
      adverse event rates with combination inhalers using different doses of inhaled
      corticosteroids. Evidence from head-to-head comparisons is needed to assess the
      comparative risks and benefits of the different combination inhalers.

PMID- 22972101
TI  - Repositioning for treating pressure ulcers.
AB  - BACKGROUND: Pressure, from lying or sitting on a particular part of the body
      results in reduced oxygen and nutrient supply, impaired drainage of waste
      products and damage to cells. If a patient with an existing pressure ulcer
      continues to lie or bear weight on the affected area, the tissues become depleted
      of blood flow and there is no oxygen or nutrient supply to the wound, and no
      removal of waste products from the wound, all of which are necessary for healing.
      Patients who cannot reposition themselves require assistance. International best
      practice advocates the use of repositioning as an integral component of a
      pressure ulcer management strategy. This review has been conducted to clarify the
      role of repositioning in the management of patients with pressure ulcers.
      OBJECTIVES: To assess the effects of repositioning patients on the healing rates
      of pressure ulcers. SEARCH METHODS: For this second update we searched the
      Cochrane Wounds Group Specialised Register (searched 23 May 2012); The Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      5); Ovid MEDLINE (2010 to May Week 2 2012); Ovid MEDLINE (In-Process & Other Non
      Indexed Citations May 22, 2012); Ovid EMBASE (2010 to 2012 Week 20); and EBSCO
      CINAHL (2010 to 16 May 2012). SELECTION CRITERIA: We considered randomised
      controlled trials (RCTs) comparing repositioning with no repositioning, or RCTs
      comparing different repositioning techniques, or RCTs comparing different
      repositioning frequencies for the review. Controlled clinical trials (CCTs) were
      only to be considered in the absence of RCTs. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed titles and, where available, abstracts of the
      studies identified by the search strategy for their eligibility. We obtained full
      versions of potentially relevant studies and two authors independently screened
      these against the inclusion criteria. MAIN RESULTS: We identified no studies that
      met the inclusion criteria. AUTHORS' CONCLUSIONS: Despite the widespread use of
      repositioning as a component of the management plan for individuals with existing
      pressure ulcers, no randomised trials exist that assess the effects of
      repositioning patients on the healing rates of pressure ulcers. Therefore, we
      cannot conclude whether repositioning patients improves the healing rates of
      pressure ulcers. The effect of repositioning on pressure ulcer healing needs to
      be evaluated.

PMID- 22972102
TI  - Techniques of intrauterine fetal transfusion for women with red-cell
      isoimmunisation for improving health outcomes.
AB  - BACKGROUND: Red-cell alloimmunisation can occur when there are incompatibilities
      between a woman's blood type and that of her unborn baby. This can cause the baby
      to become anaemic (low red blood cell count), which may require treatment during
      the pregnancy by blood transfusion while the baby remains within the uterus
      (called an intrauterine blood transfusion). OBJECTIVES: To compare, using the
      best available evidence, the benefits and harms of different techniques of
      intrauterine fetal blood transfusion for women with red-cell alloimmunisation.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (13 June 2012). SELECTION CRITERIA: We considered randomised controlled
      trials comparing different techniques of intrauterine fetal blood transfusion
      (either alone or in combination with another technique) for inclusion. DATA
      COLLECTION AND ANALYSIS: Two authors evaluated trials under consideration for
      appropriateness for inclusion and methodological quality, without consideration
      of their results according to the prestated eligibility criteria. We planned to
      use a fixed-effect meta-analysis for combining study data if we judged the trials
      to be sufficiently similar. We planned to investigate statistical heterogeneity
      using the I2 statistic; if this indicated a high degree of statistical
      heterogeneity, we planned to use a random-effects model. MAIN RESULTS: Our search
      strategy identified four reports of three studies for consideration, of which two
      met the inclusion criteria, involving 44 women. We identified a single trial
      comparing the use of intrauterine fetal blood transfusion and intravenous
      immunoglobulin versus intrauterine fetal blood transfusion alone, and a single
      trial comparing the use of atracurium and pancuronium. There were no
      statistically significant differences identified for any of the reported
      outcomes. AUTHORS' CONCLUSIONS: There is little available high quality
      information from randomised controlled trials to inform the optimal procedural
      technique when performing fetal intrauterine fetal blood transfusions for women
      with an anaemic fetus due to red cell alloimmunisation. Further research
      evaluating the benefits and harms associated with different techniques is
      required.

PMID- 22972103
TI  - Interventions for preventing falls in older people living in the community.
AB  - BACKGROUND: Approximately 30% of people over 65 years of age living in the
      community fall each year. This is an update of a Cochrane review first published
      in 2009. OBJECTIVES: To assess the effects of interventions designed to reduce
      the incidence of falls in older people living in the community. SEARCH METHODS:
      We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register
      (February 2012), CENTRAL (The Cochrane Library 2012, Issue 3), MEDLINE (1946 to
      March 2012), EMBASE (1947 to March 2012), CINAHL (1982 to February 2012), and
      online trial registers. SELECTION CRITERIA: Randomised trials of interventions to
      reduce falls in community-dwelling older people. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed risk of bias and extracted data. We
      used a rate ratio (RaR) and 95% confidence interval (CI) to compare the rate of
      falls (e.g. falls per person year) between intervention and control groups. For
      risk of falling, we used a risk ratio (RR) and 95% CI based on the number of
      people falling (fallers) in each group. We pooled data where appropriate. MAIN
      RESULTS: We included 159 trials with 79,193 participants. Most trials compared a
      fall prevention intervention with no intervention or an intervention not expected
      to reduce falls. The most common interventions tested were exercise as a single
      intervention (59 trials) and multifactorial programmes (40 trials). Sixty-two per
      cent (99/159) of trials were at low risk of bias for sequence generation, 60% for
      attrition bias for falls (66/110), 73% for attrition bias for fallers (96/131),
      and only 38% (60/159) for allocation concealment.Multiple-component group
      exercise significantly reduced rate of falls (RaR 0.71, 95% CI 0.63 to 0.82; 16
      trials; 3622 participants) and risk of falling (RR 0.85, 95% CI 0.76 to 0.96; 22
      trials; 5333 participants), as did multiple-component home-based exercise (RaR
      0.68, 95% CI 0.58 to 0.80; seven trials; 951 participants and RR 0.78, 95% CI
      0.64 to 0.94; six trials; 714 participants). For Tai Chi, the reduction in rate
      of falls bordered on statistical significance (RaR 0.72, 95% CI 0.52 to 1.00;
      five trials; 1563 participants) but Tai Chi did significantly reduce risk of
      falling (RR 0.71, 95% CI 0.57 to 0.87; six trials; 1625
      participants).Multifactorial interventions, which include individual risk
      assessment, reduced rate of falls (RaR 0.76, 95% CI 0.67 to 0.86; 19 trials; 9503
      participants), but not risk of falling (RR 0.93, 95% CI 0.86 to 1.02; 34 trials;
      13,617 participants).Overall, vitamin D did not reduce rate of falls (RaR 1.00,
      95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR
      0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in
      people with lower vitamin D levels before treatment.Home safety assessment and
      modification interventions were effective in reducing rate of falls (RR 0.81, 95%
      CI 0.68 to 0.97; six trials; 4208 participants) and risk of falling (RR 0.88, 95%
      CI 0.80 to 0.96; seven trials; 4051 participants). These interventions were more
      effective in people at higher risk of falling, including those with severe visual
      impairment. Home safety interventions appear to be more effective when delivered
      by an occupational therapist.An intervention to treat vision problems (616
      participants) resulted in a significant increase in the rate of falls (RaR 1.57,
      95% CI 1.19 to 2.06) and risk of falling (RR 1.54, 95% CI 1.24 to 1.91). When
      regular wearers of multifocal glasses (597 participants) were given single lens
      glasses, all falls and outside falls were significantly reduced in the subgroup
      that regularly took part in outside activities. Conversely, there was a
      significant increase in outside falls in intervention group participants who took
      part in little outside activity.Pacemakers reduced rate of falls in people with
      carotid sinus hypersensitivity (RaR 0.73, 95% CI 0.57 to 0.93; three trials; 349
      participants) but not risk of falling. First eye cataract surgery in women
      reduced rate of falls (RaR 0.66, 95% CI 0.45 to 0.95; one trial; 306
      participants), but second eye cataract surgery did not.Gradual withdrawal of
      psychotropic medication reduced rate of falls (RaR 0.34, 95% CI 0.16 to 0.73; one
      trial; 93 participants), but not risk of falling. A prescribing modification
      programme for primary care physicians significantly reduced risk of falling (RR
      0.61, 95% CI 0.41 to 0.91; one trial; 659 participants).An anti-slip shoe device
      reduced rate of falls in icy conditions (RaR 0.42, 95% CI 0.22 to 0.78; one
      trial; 109 participants). One trial (305 participants) comparing multifaceted
      podiatry including foot and ankle exercises with standard podiatry in people with
      disabling foot pain significantly reduced the rate of falls (RaR 0.64, 95% CI
      0.45 to 0.91) but not the risk of falling.There is no evidence of effect for
      cognitive behavioural interventions on rate of falls (RaR 1.00, 95% CI 0.37 to
      2.72; one trial; 120 participants) or risk of falling (RR 1.11, 95% CI 0.80 to
      1.54; two trials; 350 participants).Trials testing interventions to increase
      knowledge/educate about fall prevention alone did not significantly reduce the
      rate of falls (RaR 0.33, 95% CI 0.09 to 1.20; one trial; 45 participants) or risk
      of falling (RR 0.88, 95% CI 0.75 to 1.03; four trials; 2555 participants).No
      conclusions can be drawn from the 47 trials reporting fall-related
      fractures.Thirteen trials provided a comprehensive economic evaluation. Three of
      these indicated cost savings for their interventions during the trial period:
      home-based exercise in over 80-year-olds, home safety assessment and modification
      in those with a previous fall, and one multifactorial programme targeting eight
      specific risk factors. AUTHORS' CONCLUSIONS: Group and home-based exercise
      programmes, and home safety interventions reduce rate of falls and risk of
      falling.Multifactorial assessment and intervention programmes reduce rate of
      falls but not risk of falling; Tai Chi reduces risk of falling.Overall, vitamin D
      supplementation does not appear to reduce falls but may be effective in people
      who have lower vitamin D levels before treatment.

PMID- 22972104
TI  - Cinnamon for diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disorder that is associated
      with an increased risk of cardiovascular disease, retinopathy, nephropathy,
      neuropathy, sexual dysfunction and periodontal disease. Improvements in glycaemic
      control may help to reduce the risk of these complications. Several animal
      studies show that cinnamon may be effective in improving glycaemic control. While
      these effects have been explored in humans also, findings from these studies have
      not yet been systematically reviewed. OBJECTIVES: To evaluate the effects of
      cinnamon in patients with diabetes mellitus. SEARCH METHODS: Pertinent randomised
      controlled trials were identified through AARP Ageline, AMED, AMI, BioMed Central
      gateway, CAM on PubMed, CINAHL, Dissertations Abstracts International, EMBASE,
      Health Source Nursing/Academic edition, International Pharmaceutical Abstracts,
      MEDLINE, Natural medicines comprehensive database, The Cochrane Library and TRIP
      database. Clinical trial registers and the reference lists of included trials
      were searched also (all up to January 2012). Content experts and manufacturers of
      cinnamon extracts were also contacted. SELECTION CRITERIA: All randomised
      controlled trials comparing the effects of orally administered monopreparations
      of cinnamon (Cinnamomum spp.) to placebo, active medication or no treatment in
      persons with either type 1 or type 2 diabetes mellitus. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials, assessed risk of bias
      and trial quality, and extracted data. We contacted study authors for missing
      information. MAIN RESULTS: Ten prospective, parallel-group design, randomised
      controlled trials, involving a total of 577 participants with type 1 and type 2
      diabetes mellitus, were identified. Risk of bias was high or unclear in all but
      two trials, which were assessed as having moderate risk of bias. Risk of bias in
      some domains was high in 50% of trials. Oral monopreparations of cinnamon
      (predominantly Cinnamomum cassia) were administered at a mean dose of 2 g daily,
      for a period ranging from 4 to 16 weeks. The effect of cinnamon on fasting blood
      glucose level was inconclusive. No statistically significant difference in
      glycosylated haemoglobin A1c (HbA1c), serum insulin or postprandial glucose was
      found between cinnamon and control groups. There were insufficient data to pool
      results for insulin sensitivity. No trials reported health-related quality of
      life, morbidity, mortality or costs. Adverse reactions to oral cinnamon were
      infrequent and generally mild in nature. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support the use of cinnamon for type 1 or type 2
      diabetes mellitus. Further trials, which address the issues of allocation
      concealment and blinding, are now required. The inclusion of other important
      endpoints, such as health-related quality of life, diabetes complications and
      costs, is also needed.

PMID- 22972105
TI  - Black cohosh (Cimicifuga spp.) for menopausal symptoms.
AB  - BACKGROUND: Menopause can be a distressing and disruptive time for many women,
      with many experiencing hot flushes, night sweats, vaginal atrophy and dryness.
      Postmenopausal women are also at increased risk of osteoporosis. Interventions
      that decrease the severity and frequency of these menopausal symptoms are likely
      to improve a woman's well-being and quality of life. Hormone therapy has been
      shown to be effective in controlling the symptoms of menopause; however, many
      potentially serious adverse effects have been associated with this treatment.
      Evidence from experimental studies suggests that black cohosh may be a
      biologically plausible alternative treatment for menopause; even so, findings
      from studies investigating the clinical effectiveness of black cohosh have, to
      date, been inconsistent. OBJECTIVES: To evaluate the clinical effectiveness and
      safety of black cohosh (Cimicifuga racemosa or Actaea racemosa) for treating
      menopausal symptoms in perimenopausal and postmenopausal women. SEARCH METHODS:
      Relevant studies were identified through AARP Ageline, AMED, AMI, BioMed Central
      gateway, CAM on PubMed, CINAHL, CENTRAL, EMBASE, Health Source Nursing/Academic
      edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines
      comprehensive database, PsycINFO, TRIP database, clinical trial registers and the
      reference lists of included trials; up to March 2012. Content experts and
      manufacturers of black cohosh extracts were also contacted. SELECTION CRITERIA:
      All randomised controlled trials comparing orally administered monopreparations
      of black cohosh to placebo or active medication in perimenopausal and
      postmenopausal women. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials, extracted data and completed the 'Risk of bias'
      assessment. Study authors were contacted for missing information. MAIN RESULTS:
      Sixteen randomised controlled trials, recruiting a total of 2027 perimenopausal
      or postmenopausal women, were identified. All studies used oral monopreparations
      of black cohosh at a median daily dose of 40 mg, for a mean duration of 23 weeks.
      Comparator interventions included placebo, hormone therapy, red clover and
      fluoxetine. Reported outcomes included vasomotor symptoms, vulvovaginal symptoms,
      menopausal symptom scores and adverse effects. There was no significant
      difference between black cohosh and placebo in the frequency of hot flushes (mean
      difference (MD) 0.07 flushes per day; 95% confidence interval (CI) -0.43 to 0.56
      flushes per day; P=0.79; 393 women; three trials; moderate heterogeneity: I(2) =
      47%) or in menopausal symptom scores (standardised mean difference (SMD) -0.10;
      95% CI -0.32 to 0.11; P = 0.34; 357 women; four trials; low heterogeneity: I(2) =
      21%). Compared to black cohosh, hormone therapy significantly reduced daily hot
      flush frequency (three trials; data not pooled) and menopausal symptom scores
      (SMD 0.32; 95% CI 0.13 to 0.51; P=0.0009; 468 women; five trials; substantial
      heterogeneity: I(2) = 69%). These findings should be interpreted with caution
      given the heterogeneity between studies. Comparisons of the effectiveness of
      black cohosh and other interventions were either inconclusive (because of
      considerable heterogeneity or an insufficient number of studies) or not
      statistically significant. Similarly, evidence on the safety of black cohosh was
      inconclusive, owing to poor reporting. There were insufficient data to pool
      results for health-related quality of life, sexuality, bone health, vulvovaginal
      atrophic symptoms and night sweats. No trials reported cost-effectiveness data.
      The quality of included trials was generally unclear, owing to inadequate
      reporting. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to
      support the use of black cohosh for menopausal symptoms. However, there is
      adequate justification for conducting further studies in this area. The uncertain
      quality of identified trials highlights the need for improved reporting of study
      methods, particularly with regards to allocation concealment and the handling of
      incomplete outcome data. The effect of black cohosh on other important outcomes,
      such as health-related quality of life, sexuality, bone health, night sweats and
      cost-effectiveness also warrants further investigation.

PMID- 22972106
TI  - Perioperative glycaemic control for diabetic patients undergoing surgery.
AB  - BACKGROUND: Patients with diabetes mellitus are at increased risk of
      postoperative complications. Data from randomised clinical trials and meta
      analyses point to a potential benefit of intensive glycaemic control, targeting
      near-normal blood glucose, in patients with hyperglycaemia (with and without
      diabetes mellitus) being submitted to surgical procedures. However, there is
      limited evidence concerning this question in patients with diabetes mellitus
      undergoing surgery. OBJECTIVES: To assess the effects of perioperative glycaemic
      control for diabetic patients undergoing surgery. SEARCH METHODS: Trials were
      obtained from searches of The Cochrane Library, MEDLINE, EMBASE, LILACS, CINAHL
      and ISIS (all up to February 2012). SELECTION CRITERIA: We included randomised
      controlled clinical trials that prespecified different targets of perioperative
      glycaemic control (intensive versus conventional or standard care) DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      risk of bias. We summarised studies using meta-analysis or descriptive methods.
      MAIN RESULTS: Twelve trials randomised 694 diabetic participants to intensive
      control and 709 diabetic participants to conventional glycaemic control. The
      duration of the intervention ranged from just the duration of the surgical
      procedure up to 90 days. The number of participants ranged from 13 to 421, and
      the mean age was 64 years. Comparison of intensive with conventional glycaemic
      control demonstrated the following results for our predefined primary outcomes:
      analysis restricted to studies with low or unclear detection or attrition bias
      for infectious complications showed a risk ratio (RR) of 0.46 (95% confidence
      interval (CI) 0.18 to 1.18), P = 0.11, 627 participants, eight trials, moderate
      quality of the evidence (grading of recommendations assessment, development and
      evaluation - (GRADE)). Evaluation of death from any cause revealed a RR of 1.19
      (95% CI 0.89 to 1.59), P = 0.24, 1365 participants, 11 trials, high quality of
      the evidence (GRADE).On the basis of a posthoc analysis, there is the hypothesis
      that intensive glycaemic control may increase the risk of hypoglycaemic episodes
      if longer-term outcome measures are analysed (RR 6.92, 95% CI 2.04 to 23.41), P =
      0.002, 724 patients, three trials, low quality of the evidence (GRADE). Analysis
      of our predefined secondary outcomes revealed the following findings:
      cardiovascular events had a RR of 1.03 (95% CI 0.21 to 5.13), P = 0.97, 682
      participants, six trials, moderate quality of the evidence (GRADE) when comparing
      the two treatment modalities; and renal failure also did not show significant
      differences between intensive and regular glucose control (RR 0.61, 95% CI 0.34
      to 1.08), P = 0.09, 434 participants, two trials, moderate quality of the
      evidence (GRADE). We did not meta-analyse length of hospital stay and intensive
      care unit (ICU) stay due to substantial unexplained heterogeneity. Mean
      differences between intensive and regular glucose control groups ranged from -1.7
      days to 2.1 days for ICU stay and between -8 days to 3.7 days for hospital stay
      (moderate quality of the evidence (GRADE)). One trial assessed health-related
      quality of life in 12/37 (32.4%) of participants in the intervention group and
      13/44 (29.5%) of participants in the control group, and did not show an important
      difference (low quality of the evidence (GRADE)) in the measured physical health
      composite score of the short-form 12-item health survey (SF-12). None of the
      trials examined the effects of the interventions in terms of costs. AUTHORS'
      CONCLUSIONS: The included trials did not demonstrate significant differences for
      most of the outcomes when targeting intensive perioperative glycaemic control
      compared with conventional glycaemic control in patients with diabetes mellitus.
      However, posthoc analysis indicated that intensive glycaemic control was
      associated with an increased number of patients experiencing hypoglycaemic
      episodes. Intensive glycaemic control protocols with near-normal blood glucose
      targets for patients with diabetes mellitus undergoing surgical procedures are
      currently not supported by an adequate scientific basis. We suggest that insulin
      treatment regimens, patient- and health-system relevant outcomes, and time points
      for outcome measures should be defined in a thorough and uniform way in future
      studies.

PMID- 22972107
TI  - Disease modifying anti-rheumatic drugs in people with cystic fibrosis-related
      arthritis.
AB  - BACKGROUND: Arthritis remains a relatively infrequent complication of cystic
      fibrosis, but is a cause of significant morbidity when it does occur. Two
      distinct types of arthritis are described in cystic fibrosis: cystic fibrosis
      related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in
      people with cystic fibrosis is uncertain and complex because of the underlying
      disease and its treatment. OBJECTIVES: To review the effectiveness and safety of
      disease-modifying anti-rheumatic drugs for the management of arthritis related to
      cystic fibrosis in adults and children. SEARCH METHODS: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which
      comprises references identified from comprehensive electronic database
      handsearches of relevant journal and abstract books of conference
      proceedings.Date of most recent search: 10 July 2012. SELECTION CRITERIA:
      Randomised controlled trials which compared the efficacy and safety of disease
      modifying anti-rheumatic drugs (e.g. methotrexate, gold, sulfasalazine,
      penicillamine, leflunomide, hydroxychloroquine and newer agents such as biologic
      disease modifying agents and monoclonal antibodies) with each other, with no
      treatment or with placebo for cystic fibrosis-related arthropathy or hypertrophic
      osteoarthropathy. DATA COLLECTION AND ANALYSIS: No relevant studies were
      identified. MAIN RESULTS: No studies were included in this review. AUTHORS'
      CONCLUSIONS: Although it is generally recognised that cystic fibrosis-related
      arthritis can be episodic and resolve spontaneously, treatment with analgesics
      and anti-inflammatory agents may be needed. But when episodic symptoms progress
      to persistent disease, disease-modifying anti-rheumatic drugs may be needed to
      limit the course of the disease. It is disappointing that no randomised
      controlled trials to rigorously evaluate these drugs could be found. This
      systematic review has identified the need for a well-designed adequately powered
      randomised controlled trial to assess the efficacy and safety of disease
      modifying anti-rheumatic drugs for the management of cystic fibrosis-related
      arthropathy and hypertrophic osteoarthropathy in adults and children with cystic
      fibrosis. However, given the infrequency of cystic fibrosis-related arthritis and
      the range of symptoms and severity, randomised controlled trials may not be
      feasible and well-designed non-randomised observational studies may be more
      appropriate. Studies should also better define the two conditions.

PMID- 22972108
TI  - Topical NSAIDs for chronic musculoskeletal pain in adults.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken
      orally, but they are also available in topical preparations to be applied to or
      rubbed onto the skin of a painful joint, typically one affected by arthritis,
      with the aim of relieving pain locally. Topical NSAIDs are widely used in some
      parts of the world for acute and chronic painful conditions, but have not been
      universally accepted until recently. One of the problems has been that older
      clinical studies were generally short, lasting four weeks or less, and short
      duration studies are not regarded as adequate in ongoing painful conditions.
      OBJECTIVES: To examine the use of topical NSAIDs in chronic musculoskeletal pain,
      focusing on studies of high methodological quality, and examining the measured
      effect of the preparations according to study duration. The principal aim was to
      estimate treatment efficacy in longer duration studies of at least 8 weeks.
      SEARCH METHODS: A series of electronic searches, together with bibliographic
      searches, and searches of in-house databases were combined with electronic
      searches of clinical trial registers and manufacturers of topical NSAIDs, or
      companies known to be actively researching topical NSAIDs. There had to be at
      least 10 participants in each treatment arm, with application of treatment at
      least once daily. SELECTION CRITERIA: Randomised, double blind studies with
      placebo or active comparators, where at least one treatment was a topical NSAID
      product, in any topical formulation (cream, gel, patch, solution), in studies
      lasting at least two weeks. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study quality and validity, and extracted data. Numbers of
      participants achieving each outcome were used to calculate relative risk (RR) and
      numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active
      treatment. MAIN RESULTS: Information was available from 7688 participants in 34
      studies from 32 publications; 23 studies compared a topical NSAID with placebo.
      Topical NSAIDs were significantly more effective than placebo for reducing pain
      due to chronic musculoskeletal conditions. The best data were for topical
      diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8
      to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel
      formulation. There were too few data of good quality to calculate NNTs for other
      individual topical NSAIDs compared with placebo. Direct comparison of topical
      NSAID with an oral NSAID did not show any difference in efficacy. There was an
      increase in local adverse events (mostly mild skin reactions) with topical NSAIDs
      compared with placebo or oral NSAIDs, but no increase in serious adverse events.
      Gastrointestinal adverse events with topical NSAID did not differ from placebo,
      but were less frequent than with oral NSAIDs.A substantial amount of data from
      unpublished studies was unavailable. Much of this probably relates to
      formulations that have never been marketed. AUTHORS' CONCLUSIONS: Topical NSAIDs
      can provide good levels of pain relief; topical diclofenac solution is equivalent
      to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence
      for other chronic painful conditions. Formulation can influence efficacy. The
      incidence of local adverse events is increased with topical NSAIDs, but
      gastrointestinal adverse events are reduced compared with oral NSAIDs.

PMID- 22972109
TI  - Skin preparation for preventing infection following caesarean section.
AB  - BACKGROUND: The risk of maternal mortality and morbidity (particularly
      postoperative infection) is higher for caesarean section than for vaginal birth.
      With the increase in caesarean section, it is important that the risks to the
      mother are minimised as far as possible. This review focuses on different forms
      and methods for preoperative skin preparation to prevent infection. OBJECTIVES:
      To compare the effects of different agent forms and methods of preoperative skin
      preparation for preventing postcaesarean infection. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (2 January 2012)
      and the reference lists of all included studies and review articles SELECTION
      CRITERIA: Randomised and quasi-randomised trials, including cluster-randomised
      trials, evaluating any type of preoperative skin preparation agents, forms and
      methods of application for caesarean section. DATA COLLECTION AND ANALYSIS: Three
      review authors independently assessed all potential studies for inclusion,
      assessed risk of bias and extracted the data using a predesigned form. Data were
      checked for accuracy. MAIN RESULTS: We included five trials with a total of 1462
      women. No difference was found in the primary outcomes of either wound infection
      or endometritis. Two trials of 1294 women, compared drape with no drape (one
      trial using iodine and the other using chlorhexidine) and found no significant
      difference in wound infection (risk ratio (RR) 1.29; 95% confidence interval (CI)
      0.97 to 1.71). One trial of 79 women comparing alcohol scrub and iodophor drape
      with iodophor scrub without drape reported no wound infection in either group.
      One trial of 50 women comparing parachlorometaxylenol plus iodine with iodine
      alone reported no significant difference in wound infection (RR 0.33; 95% CI 0.04
      to 2.99).Two trials reported endometritis, one trial comparing alcohol scrub and
      iodophor drape with iodophor scrub only found no significant difference (RR 1.62;
      95% CI 0.29 to 9.16). The other trial of 50 women comparing parachlorometaxylenol
      plus iodine with iodine alone reported no significant difference in endometritis
      (RR 0.88; 95% CI 0.56 to 1.38). No difference was found in the secondary outcome
      of either length of stay or reduction of skin bacteria colony count. No trial
      reported other maternal outcomes, i.e. maternal mortality, repeat surgery and re
      admission resulting from infection. One trial, which was only available as an
      abstract, investigated the effect of skin preparation on neonatal adverse events
      and found cord blood iodine concentration to be significantly higher in the
      iodine group. AUTHORS' CONCLUSIONS: Little evidence is available from the
      included randomised controlled trials to evaluate different agent forms,
      concentrations and methods of skin preparation for preventing infection following
      caesarean section. Therefore, it is not yet clear what sort of skin preparation
      may be most efficient for preventing postcaesarean wound and surgical site
      infection. There is a need for high-quality, properly designed randomised
      controlled trials with larger sample sizes in this field. High priority questions
      include comparing types of antiseptic (especially iodine versus chlorhexidine),
      the timing and duration of applying the antiseptic (especially previous night
      versus day of surgery, and application methods (scrubbing, swabbing and draping).

PMID- 22972110
TI  - Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract
      infections.
AB  - BACKGROUND: Acute respiratory infections (ARIs) comprise a large and
      heterogeneous group of infections including bacterial, viral and other
      aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has
      emerged as a promising marker for the diagnosis of bacterial infections and for
      improving decisions about antibiotic therapy. Several randomised controlled
      trials (RCTs) have demonstrated the feasibility of using procalcitonin for
      starting and stopping antibiotics in different patient populations with acute
      respiratory infections and different settings ranging from primary care to
      emergency departments (EDs), hospital wards and intensive care units (ICUs).
      OBJECTIVES: The aim of this systematic review based on individual patient data
      was to assess the safety and efficacy of using procalcitonin for starting or
      stopping antibiotics over a large range of patients with varying severity of ARIs
      and from different clinical settings. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the
      Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May
      2011) and EMBASE (1974 to May 2011) to identify suitable trials. SELECTION
      CRITERIA: We included RCTs of adult participants with ARIs who received an
      antibiotic treatment either based on a procalcitonin algorithm or usual
      care/guidelines. Trials were excluded if they exclusively focused on paediatric
      patients or if they used procalcitonin for another purpose than to guide
      initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS:
      Two teams of review authors independently evaluated the methodology and extracted
      data from primary studies. The primary endpoints were all-cause mortality and
      treatment failure at 30 days. For the primary care setting, treatment failure was
      defined as death, hospitalisation, ARI-specific complications, recurrent or
      worsening infection, and patients reporting any symptoms of an ongoing
      respiratory infection at follow-up. For the ED setting, treatment failure was
      defined as death, ICU admission, re-hospitalisation after index hospital
      discharge, ARI-associated complications, and recurrent or worsening infection
      within 30 days of follow-up. For the ICU setting, treatment failure was defined
      as death within 30 days of follow-up. Secondary endpoints were antibiotic use
      (initiation of antibiotics, duration of antibiotics and total exposure to
      antibiotics (total amount of antibiotic days divided by total number of
      patients)), length of hospital stay for hospitalised patients, length of ICU stay
      for critically ill patients, and number of days with restricted activities within
      14 days after randomisation for primary care patients.For the two co-primary
      endpoints of all-cause mortality and treatment failure, we calculated odds ratios
      (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical
      logistic regression. The hierarchical regression model was adjusted for age and
      clinical diagnosis as fixed-effect. The different trials were added as random
      effects into the model. We fitted corresponding linear regression models for
      antibiotic use. We conducted sensitivity analyses stratified by clinical setting
      and ARI diagnosis to assess the consistency of our results. MAIN RESULTS: We
      included 14 trials with 4221 participants. There were 118 deaths in 2085 patients
      (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control
      patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure
      occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients
      (21.9%). Procalcitonin guidance was not associated with increased mortality or
      treatment failure in any clinical setting, or ARI diagnosis. These results proved
      robust in various sensitivity analyses. Total antibiotic exposure was
      significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4
      (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and
      across all the different clinical settings and diagnoses. AUTHORS' CONCLUSIONS:
      Use of procalcitonin to guide initiation and duration of antibiotic treatment in
      patients with ARI was not associated with higher mortality rates or treatment
      failure. Antibiotic consumption was significantly reduced across different
      clinical settings and ARI diagnoses. Further high-quality research is needed to
      confirm the safety of this approach for non-European countries and patients in
      intensive care. Moreover, future studies should also establish cost-effectiveness
      by considering country-specific costs of procalcitonin measurement and potential
      savings in consumption of antibiotics and other healthcare resources, as well as
      secondary cost savings due to lower risk of side effects and reduced
      antimicrobial resistance.

PMID- 22972111
TI  - Unfractionated heparin versus low molecular weight heparin for avoiding heparin
      induced thrombocytopenia in postoperative patients.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction
      presenting as a prothrombotic disorder related to antibody-mediated platelet
      activation. It is a poorly understood paradoxical immune reaction resulting in
      thrombin generation in vivo, which leads to a hypercoagulable state and the
      potential to initiate venous or arterial thrombosis. A number of factors are
      thought to influence the incidence of HIT including the type and preparation of
      heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and
      the heparin-exposed patient population, with the postoperative patient population
      presenting a higher risk.Although LMWH has largely replaced UFH as a front-line
      therapy, there is evidence supporting a lack of superiority of LMWH compared with
      UFH regarding prevention of deep vein thrombosis and pulmonary embolism following
      surgery, and similar frequencies of bleeding have been described with LMWH and
      UFH. The decision as to which of these two preparations of heparin to use may
      thus be influenced by adverse reactions such as HIT. We therefore sought to
      determine the relative impact of UFH and LMWH specifically on HIT in
      postoperative patients receiving thromboembolism prophylaxis. OBJECTIVES: The
      objective of this review was to compare the incidence of HIT and HIT complicated
      by thrombosis in patients exposed to UFH versus LMWH in randomised controlled
      trials (RCTs) of postoperative heparin therapy. SEARCH METHODS: The Cochrane
      Peripheral Vascular Diseases Group searched their Specialised Register (March
      2012) and CENTRAL (2012, Issue 2). In addition, the authors searched LILACS
      (March 2012) and additional trials were sought from reference lists of relevant
      publications. SELECTION CRITERIA: We were interested in comparing the incidence
      of HIT occurring during exposure to UFH or LMWH after any surgical intervention.
      Therefore, we studied RCTs in which participants were postoperative patients
      allocated to receive UFH or LMWH, in a blinded or unblinded fashion. Eligible
      studies were required to have as an outcome clinically diagnosed HIT, defined as
      a relative reduction in the platelet count of 50% or greater from the
      postoperative peak (even if the platelet count at its lowest remained > 150 x
      10(9)/L) occurring within five to 14 days after the surgery, with or without a
      thrombotic event occurring in this timeframe. Additionally, circulating
      antibodies associated with the syndrome were required to have been investigated
      through laboratory assays. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed the risk of bias. Disagreements were
      resolved by consensus with participation of a third author. MAIN RESULTS: In
      total two studies involving 923 participants met all the inclusion criteria and
      were included in the review. Pooled analysis showed a statistically significant
      reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.24,
      95% confidence interval (CI) 0.07 to 0.82; P = 0.02). This result suggests that
      patients treated with LMWH would have a relative risk reduction (RRR) of 76% in
      the probability of developing HIT compared with patients treated with UFH.Venous
      thromboembolism (VTE) complicating HIT occurred in 12 of 17 patients who
      developed HIT. Pooled analysis showed a statistically significant reduction in
      HIT complicated by VTE with LMWH compared with UFH (RR 0.20, 95% CI 0.04 to 0.90;
      P = 0.04). This result indicates that patients using LMWH would have a RRR of 80%
      for developing HIT complicated by VTE compared with patients using UFH. Arterial
      thrombosis occurred in only one patient who received UFH and there were no
      amputations or deaths documented. AUTHORS' CONCLUSIONS: There was a lower
      incidence of HIT and HIT complicated by VTE in postoperative patients undergoing
      thromboprophylaxis with LMWH compared with UFH. This is consistent with the
      current clinical use of LMWH over UFH as front-line heparin therapy. However,
      conclusions are limited by a scarcity of high quality evidence. We did not expect
      the paucity of RCTs including HIT as an outcome as heparin is one of the most
      commonly used drugs worldwide and HIT is a life-threatening adverse drug
      reaction. To address the scarcity of clinically-relevant information on the topic
      of HIT as a whole, HIT should be included as an outcome in future RCTs of
      heparin, and HIT as an adverse drug reaction should be considered in clinical
      recommendations regarding monitoring of the platelet count for HIT.

PMID- 22972113
TI  - Decongestants, antihistamines and nasal irrigation for acute sinusitis in
      children.
AB  - BACKGROUND: The efficacy of decongestants, antihistamines and nasal irrigation in
      children with clinically diagnosed acute sinusitis has not been systematically
      evaluated. OBJECTIVES: To systematically review the efficacy of decongestants,
      antihistamines and nasal irrigation in children with clinically diagnosed acute
      sinusitis. We considered the following four interventions: 1) decongestants
      versus placebo or no medication, 2) antihistamines versus placebo or no
      medication, 3) decongestant and antihistamine combination versus placebo or no
      medication, 4) nasal irrigation versus no irrigation. The primary outcomes of the
      review were symptom resolution (improvement in symptom score from enrolment to
      day five and overall symptom burden (as measured by average symptom scores while
      on therapy). SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL 2012, Issue 1), which includes the Acute Respiratory
      Infections Group's Specialized Register, MEDLINE (1950 to January week 3, 2012)
      and EMBASE (1950 to January 2012). SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) and quasi-RCTs which evaluated children less than 18
      years of age with acute sinusitis, defined as 10 to 30 days of rhinorrhea,
      congestion or daytime cough. We excluded trials of children with chronic
      sinusitis and allergic rhinitis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed each study for inclusion. MAIN RESULTS: Of the 526 studies
      found through the electronic searches and handsearching, none met all the
      inclusion criteria. AUTHORS' CONCLUSIONS: There is no evidence to determine
      whether the use of antihistamines, decongestants or nasal irrigation is
      efficacious in children with acute sinusitis. Further research is needed to
      determine whether these interventions are beneficial in the treatment of children
      with acute sinusitis.

PMID- 22972114
TI  - Cryotherapy following total knee replacement.
AB  - BACKGROUND: Total knee replacement (TKR) is a common intervention for patients
      with end-stage osteoarthritis of the knee. Post-surgical management may include
      cryotherapy. However, the effectiveness of cryotherapy is unclear. OBJECTIVES: To
      evaluate the acute (within 48 hours) application of cryotherapy following TKR on
      pain, blood loss and function. SEARCH METHODS: We searched the Cochrane Database
      of Systematic Reviews, CENTRAL, DARE, HTA Database, MEDLINE, EMBASE, CINAHL,
      PEDro and Web of Science on 15th March 2012. SELECTION CRITERIA: Randomised
      controlled trials or controlled clinical trials in which the experimental group
      received any form of cryotherapy, and was compared to any control group following
      TKR indicated for osteoarthritis. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion. Disagreements were discussed and
      resolved involving a third reviewer if required. Data were then extracted and the
      risk of bias of trials assessed. Main outcomes were blood loss, visual analogue
      score (VAS) pain, adverse events, knee range of motion, transfusion rate and knee
      function. Secondary outcomes were analgesia use, knee swelling, length of
      hospital stay, quality of life and activity level. Effects of interventions were
      estimated as mean differences (MD), standardised mean differences (SMD) or given
      as risk ratios (RR), with 95% confidence intervals (CI). Meta-analyses were
      performed using the inverse variance method and pooled using random effects. MAIN
      RESULTS: Eleven randomised trials and one controlled clinical trial involving 809
      participants met the inclusion criteria. There is very low quality evidence from
      10 trials (666 participants) that cryotherapy has a small benefit on blood loss
      (SMD -0.46, 95% CI, -0.84 to -0.08), equivalent to 225mL less blood loss in
      cryotherapy group (95% CI, 39 to 410mL). This benefit may not be clinically
      significant. There was very low quality evidence from four trials (322
      participants) that cryotherapy improved visual analogue score pain at 48 hours
      (MD = -1.32 points on a 10 point scale, 95% CI, -2.37 to -0.27), but not at 24 or
      72 hours. This benefit may not be clinically significant. There was no difference
      between groups in adverse events (RR = 0.98, 95% CI, 0.28 to 3.47). There is low
      quality evidence from two trials (107 participants) for improved range of motion
      at discharge (MD 11.39 degrees of additional flexion, 95% CI 4.13 to 18.66), but
      this benefit may not be clinically significant. There was no difference between
      groups in transfusion rate (RR 2.13, 95% CI 0.04 to 109.63), and knee function
      was not measured in any trial. No significant benefit were found for analgesia
      use, swelling or length of stay. Outcomes measuring quality of life or activity
      level were not reported. AUTHORS' CONCLUSIONS: Potential benefits of cryotherapy
      on blood loss, postoperative pain, and range of motion may be too small to
      justify its use, and the quality of the evidence was very low or low for all main
      outcomes. This needs to be balanced against potential inconveniences and expenses
      of using cryotherapy. Well designed randomised trials are required to improve the
      quality of the evidence.

PMID- 22972115
TI  - Interposition vein cuff for infragenicular prosthetic bypass graft.
AB  - BACKGROUND: The use of prosthetic grafts such as polytetrafluorethylene (PTFE) or
      Dacron to bypass occluded arteries in the lower leg is an accepted practice in
      the absence of suitable autologous vein. The aim is limb salvage or functional
      improvement in critical limb ischaemia, but patency rates for below knee
      prosthetic bypasses are low. Creating a vein cuff at the distal anastomosis is
      thought to improve outcomes. Other techniques including the use of pre-cuffed
      synthetic grafts, spliced segments of vein and the creation of an arterio-venous
      fistula (AVF) are also used to improve patency. OBJECTIVES: To compare the
      beneficial effects of using vein cuffed prosthetic grafts for below knee bypass
      in critical limb ischaemia with other types of reconstruction. SEARCH METHODS:
      The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator
      searched the Specialised Register (last searched May 2012) and CENTRAL (2012,
      Issue 5) for publications comparing prosthetic infragenicular bypass using vein
      cuffs with other bypass techniques. SELECTION CRITERIA: Randomised controlled
      trials comparing interposition vein cuff prosthetic graft with autologous vein
      graft and non-cuffed prosthetic graft for infragenicular bypass in patients with
      critical limb ischaemia were included. Trials comparing vein cuff prosthetic
      grafts with or without AVF and vein cuff prosthetic grafts with pre-cuffed
      prosthetic grafts were also included. DATA COLLECTION AND ANALYSIS: The trials
      were selected and assessed independently by two review authors. MAIN RESULTS: Six
      trials with a combined total of 885 patients were included in this review. Only
      studies using prosthetic PTFE grafts were identified.Two trials compared PTFE
      graft with or without a vein cuff. In one underpowered trial for below knee
      bypass the cumulative primary patency rate was statistically significantly higher
      in the vein cuff group (80.3% versus 65.3% at 12 months and 51.8% versus 29.1% at
      24 months, P = 0.03). There was no statistically significant difference in
      secondary patency (82.9% versus 72.5% and 58.6% versus 34.9%, P = 0.14) and limb
      salvage rates (86.3% versus 71.8% and 82.6% versus 62.2%, P = 0.08) at 12 and 24
      months respectively. The other trial showed no statistically significant
      difference between the groups at three years in the below knee femoro-popliteal
      bypasses (primary patency rate 26% (95% confidence interval (CI) 18 to 38) and
      43% (95% CI 33 to 58), secondary patency rate 32% (95% CI 23 to 44) and 42% (95%
      CI 31 to 56) and limb salvage rate 64% (95% CI 54 to 75) and 61% (95% CI 50 to
      74) in the collar and no collar groups respectively). In the femoro-distal bypass
      group, the differences in primary patency, secondary patency and limb salvage
      rates were also not statistically significant at three years (primary patency
      rate 20% (95% CI 11 to 38) and 17% (95% CI 9 to 33), secondary patency rate 22%
      (95% CI 12 to 39) and 20% (95% CI 11 to 35) and limb salvage rate 59% (95% CI 46
      to 76) and 44% (95% CI 32 to 61) in the collar and no collar groups
      respectively).One trial compared pre-cuffed PTFE grafts with vein cuffed grafts.
      There was no statistically significant difference in primary patency rate (62%
      pre-cuffed PTFE versus 52% vein cuff PTFE and 49% versus 44%, P = 0.53),
      secondary patency rate (66% pre-cuffed PTFE versus 53% vein cuff PTFE and 55%
      versus 50%, P = 0.30) or limb salvage rate (75% pre-cuffed PTFE versus 72% vein
      cuff PTFE and 62% versus 65%, P = 0.88) at 12 and 24 months respectively.One
      trial compared spliced vein grafts with vein cuffed PTFE grafts. At 24 months,
      the secondary patency rate was statistically significantly higher in the spliced
      vein group (86% in the spliced vein and 52% in the vein cuff group, P < 0.05).
      There was no statistical significant difference in primary patency rate (44%
      versus 50%, P > 0.05) and limb salvage rate (94% versus 85%, P > 0.05).Two trials
      compared vein cuff PTFE grafts with and without AVF. There was no statistical
      significant difference at 24 months in primary patency rate (29% versus 36%, P =
      0.77; 32% versus 28%, P = 0.2), secondary patency rate (40% versus 40%, P = 0.89;
      28% versus 24%, P = 0.2) and limb salvage rate (65% versus 70%, P = 0.97; 62%
      versus 71%, P = 0.3). AUTHORS' CONCLUSIONS: There is evidence that a vein cuff at
      the distal anastomosis site improves primary graft patency rates for below knee
      PTFE graft, but this does not reduce the risk of limb loss. Pre-cuffed PTFE
      grafts have comparable patency and limb salvage rates to vein cuff PTFE grafts.
      The use of spliced veins improved secondary patency but this did not translate
      into improved limb salvage. The use of an AVF alone showed no added benefits.
      Evidence for a beneficial effect of vein cuffed PTFE grafts is weak and based on
      underpowered trials. A large study with a specific focus on below knee vein cuff
      prosthetic grafts, including PTFE, is required.

PMID- 22972112
TI  - Interventions for preventing nausea and vomiting in women undergoing regional
      anaesthesia for caesarean section.
AB  - BACKGROUND: Nausea and vomiting are distressing symptoms which are experienced
      commonly during caesarean section under regional anaesthesia and can also occur
      in the period following the procedure.  OBJECTIVES: To assess the efficacy of
      pharmacological and non-pharmacological interventions given prophylactically to
      prevent nausea and vomiting in women undergoing regional anaesthesia for
      caesarean section. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (27 February 2012) and reference lists of
      identified studies. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) and excluded quasi-RCTs and cross-over studies. DATA COLLECTION AND
      ANALYSIS: Review authors independently assessed the studies for inclusion,
      assessed risk of bias and carried out data extraction. Data entry was checked.  
      MAIN RESULTS: Fifty-two studies met the inclusion criteria but only 41 studies,
      involving 5046 women, provided useable data for the review involving women having
      caesareans under regional anaesthesia. The majority of the studies involved women
      undergoing elective caesarean section. Only two studies included emergency
      surgery, however, they did not stratify data according to type of surgery. The
      studies covered numerous comparisons, but the majority of studies involved 5
      HT(3) receptor antagonists, dopamine receptor antagonists, corticosteroids or
      acupressure. Studies were mainly small and of unclear quality.Three classes of
      intervention were found to be effective in at least three out of four of our
      primary outcomes (intraoperative nausea, intraoperative vomiting, postoperative
      nausea and postoperative vomiting). These interventions were 5-HT(3) antagonists,
      dopamine antagonists and sedatives. Other classes of intervention were effective
      for fewer than three of our primary outcomes.With 5-HT antagonists, we found a
      reduction in intraoperative nausea (average risk ratio (RR) 0.64, 95% confidence
      interval (CI) 0.46 to 0.88, eight studies, 720 women). There were also reductions
      in postoperative nausea (average RR 0.40, 95% CI 0.25 to 0.64, four studies, 405
      women) and vomiting (average RR 0.50, 95% CI 0.32 to 0.77, five studies, 565
      women). We did not detect a significant reduction in intraoperative vomiting
      (average RR 0.56, 95% CI 0.31 to 1.00, seven studies, 668 women).Dopamine
      antagonists demonstrated a reduction in intraoperative nausea (average RR 0.38,
      95% CI 0.25 to 0.57, nine studies, 636 women) and intraoperative vomiting
      (average 0.39, 95% CI 0.24 to 0.64, eight studies, 536 women), with similar
      reductions in postoperative nausea (average RR 0.60, 95% CI 0.40 to 0.91, five
      studies, 412 women) and vomiting (average RR 0.57, 95% CI 0.36 to 0.91, six
      studies, 472 women). These differences were observed with both metoclopramide and
      droperidol.Sedatives (most commonly propofol) demonstrated a reduction in
      intraoperative nausea (average RR 0.71, 95% CI 0.52 to 0.96, four studies, 285
      women) and intraoperative vomiting (average RR 0.42, 95% CI 0.26 to 0.68, four
      studies, 285 women), also with a reduction in postoperative nausea (average RR
      0.25, 95% CI 0.09 to 0.71, two studies 145 women) and vomiting (average RR 0.09,
      95% CI 0.03 to 0.28, two studies, 145 women).Acupressure was found to be
      effective for intraoperative nausea (average RR 0.59, 95% CI 0.38 to 0.90, six
      studies, 649 women) but not postoperative nausea (average RR 0.83, 95% CI 0.68 to
      1.00, three studies, 429 women). Acupressure was not effective at reducing
      vomiting either intraoperatively (average RR 0.74, 95% CI 0.46 to 1.18, six
      studies, 649 women) or postoperatively (average RR 0.69, 95% CI 0.45 to 1.06,
      three studies, 429 women).Other effective intervention classes included
      corticosteroids, antihistamines, and anticholinergics.There were insufficient
      data to demonstrate any class of intervention was superior to another. There were
      no significant differences observed in the comparison of combined versus single
      interventions.Few studies assessed our secondary outcomes or the incidence of
      adverse effects. However, one study showed an increase in respiratory depression
      with sedation (midazolam) compared with dopamine antagonists. AUTHORS'
      CONCLUSIONS: This review indicates that many different interventions have
      efficacy in preventing nausea and vomiting in women undergoing regional
      anaesthesia for caesarean section. There is little evidence that combinations of
      treatment are better than single agents.

PMID- 22972116
TI  - Email for clinical communication between healthcare professionals.
AB  - BACKGROUND: Email is a popular and commonly-used method of communication, but its
      use in healthcare is not routine. Where email communication has been utilised in
      health care, its purposes have included use for clinical communication between
      healthcare professionals, but the effects of using email in this way are not
      known. This review assesses the use of email for two-way clinical communication
      between healthcare professionals. OBJECTIVES: To assess the effects of healthcare
      professionals using email to communicate clinical information, on healthcare
      professional outcomes, patient outcomes, health service performance, and service
      efficiency and acceptability, when compared to other forms of communicating
      clinical information. SEARCH METHODS: We searched: the Cochrane Consumers and
      Communication Review Group Specialised Register, Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (OvidSP)
      (1950 to January 2010), EMBASE (OvidSP) (1980 to January 2010), PsycINFO (1967 to
      January 2010), CINAHL (EbscoHOST) (1982 to February 2010), and ERIC (CSA) (1965
      to January 2010). We searched grey literature: theses/dissertation repositories,
      trials registers and Google Scholar (searched July 2010). We used additional
      search methods: examining reference lists, contacting authors. SELECTION
      CRITERIA: Randomised controlled trials, quasi-randomised trials, controlled
      before and after studies and interrupted time series studies examining
      interventions in which healthcare professionals used email for communicating
      clinical information, and that took the form of 1) unsecured email 2) secure
      email or 3) web messaging. All healthcare professionals, patients and caregivers
      in all settings were considered. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed studies for inclusion, assessed the included studies' risk
      of bias, and extracted data. We contacted study authors for additional
      information. We report all measures as per the study report. MAIN RESULTS: We
      included one randomised controlled trial involving 327 patients and 159
      healthcare providers at baseline. It compared an email to physicians containing
      patient-specific osteoporosis risk information and guidelines for evaluation and
      treatment with usual care (no email). This study was at high risk of bias for the
      allocation concealment and blinding domains. The email reminder changed health
      professional actions significantly, with professionals more likely to provide
      guideline-recommended osteoporosis treatment (bone density measurement and/or
      osteoporosis medication) when compared with usual care. The evidence for its
      impact on patient behaviours/actions was inconclusive. One measure found that the
      electronic medical reminder message impacted patient behaviour positively:
      patients had a higher calcium intake, and two found no difference between the two
      groups. The study did not assess primary health service outcomes or harms.
      AUTHORS' CONCLUSIONS: As only one study was identified for inclusion, the results
      are inadequate to inform clinical practice in regard to the use of email for
      clinical communication between healthcare professionals. Future research needs to
      use high-quality study designs that take advantage of the most recent
      developments in information technology, with consideration of the complexity of
      email as an intervention, and costs.

PMID- 22972117
TI  - Primaquine for reducing Plasmodium falciparum transmission.
AB  - BACKGROUND: Mosquitoes become infected with malaria when they ingest gametocyte
      stages of the parasite from the blood of a human host. Plasmodium falciparum
      gametocytes are sensitive to the drug primaquine (PQ). The World Health
      Organization (WHO) recommends giving a single dose or short course of PQ
      alongside primary treatment for people ill with P. falciparum infection to reduce
      malaria transmission. Gametocytes themselves cause no symptoms, so this
      intervention does not directly benefit individuals. PQ causes haemolysis in some
      people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be
      safe.   OBJECTIVES: To assess whether a single dose or short course of PQ added
      to treatments for malaria caused by P. falciparum infection reduces malaria
      transmission and is safe. SEARCH METHODS: We searched the following databases up
      to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized
      Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published
      in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled
      Trials (mRCT) and the WHO trials search portal using 'malaria*', 'falciparum',
      and 'primaquine' as search terms. In addition, we searched conference proceedings
      and reference lists of included studies, and we contacted likely researchers and
      organizations for relevant trials. SELECTION CRITERIA: Trials of mass treatment
      of whole populations (or actively detected fever or malaria cases within such
      populations) with antimalarial drugs, compared to treatment with the same drug
      plus PQ; or patients with clinical malaria being treated for malaria at health
      facilities randomized to short course/single dose PQ versus no PQ. DATA
      COLLECTION AND ANALYSIS: Two authors (PMG and HG) independently screened all
      abstracts, applied inclusion criteria, and abstracted data. We sought data on the
      effect of PQ on malaria transmission intensity, participant infectiousness, the
      number of participants with gametocytes, and gametocyte density over time. We
      stratified results by primary treatment drug as this may modify any PQ effect. We
      calculated the area under the curve (AUC) for gametocyte density over time for
      comparisons for which data were available, and also sought data on haematologic
      and other adverse effects. We used GRADE guidelines to assess evidence quality,
      and this is reflected in the wording of the results: high quality ("PQ reduces
      ...."); moderate quality ("PQ probably reduces ..."); low quality ("PQ may
      reduce...."); and very low quality ("we don't know if PQ reduces...."). MAIN
      RESULTS: We included 11 individually randomized trials, with a total of 1776
      individuals. The 11 trials included 20 comparisons with partner drugs, which
      included chloroquine (CQ), sulfadoxine-pyrimethamine (SP), mefloquine (MQ),
      quinine (QN), artesunate (AS), and a variety of artemisinin combination therapies
      (ACTs). For G6PD deficiency, studies either did not test (one study), tested and
      included all (one study), included only G6PD deficient (one study), excluded G6PD
      deficient (two studies), or made no comment (six studies).None of the trials we
      included assessed effects on malaria transmission (incidence, prevalence, or
      entomological inoculation rate (EIR)) in the trial area.With non-artemisinin drug
      regimens, PQ may reduce the infectiousness to mosquitoes of individuals treated,
      based on one small study with large effects (Risk Ratio (RR) 0.06 on day 8 after
      treatment, 95% confidence interval (CI) 0 to 0.89; low quality evidence).
      Participants who received PQ had fewer circulating gametocytes up to day 43
      (log(10) AUC relative decrease from 24.3 to 27.1%, one study (two comparisons),
      moderate quality evidence); and there were 38% fewer people with gametocytes on
      day 8 (RR 0.62, 95% CI 0.51 to 0.76, four studies (five comparisons), moderate
      quality evidence). We did not identify any study that looked for effects of the
      drug on haemolytic anaemia.With artemisinin-based drug regimens, we do not know
      if PQ influences infectiousness to mosquitoes, as no study has examined this
      directly. PQ probably reduces infectiousness, based on reduction in log(10) AUC
      (relative decrease range from 26.1% to 87.5%, two studies (six comparisons),
      moderate quality evidence); and reduces by 88% the number of participants with
      gametocytes on day 8 (RR 0.12, 95% CI 0.08 to 0.20, four studies (eight
      comparisons), moderate quality evidence).When used with artemisinin-based
      regimens, we do not know if PQ results in haemolytic anaemia; one trial reported
      percent change in mean haemoglobin against baseline, and for the PQ group this
      indicated a significantly greater drop at day 8 in those given PQ (very low
      quality evidence). Overall, the safety of PQ used in single dose or short course
      was poorly evaluated.  AUTHORS' CONCLUSIONS: We do not know whether PQ added to
      treatment regimens for patients with P. falciparum infection reduces transmission
      of malaria. In individual patients, it reduces gametocyte prevalence and density.
      In practical terms, even if PQ results in large reductions in gametocytes in
      people being treated for malaria, there is no reliable evidence that this will
      reduce transmission in a malaria-endemic community, where many people are
      infected but have no symptoms and are unlikely to be treated. Since PQ is acting
      as a monotherapy against gametocytes, there is a risk of the parasite developing
      resistance to the drug. In terms of harms, there is insufficient evidence from
      trials to know whether the drug can be used safely in this way in populations
      where G6PD deficiency occurs.In light of these doubts about safety, and lack of
      evidence of any benefit in reducing transmission, countries should question
      whether to continue to use PQ routinely in primary treatment of malaria. Further
      synthesis of observational data on safety and new trials may help elucidate a
      role for PQ in malaria elimination, or in situations where most infected
      individuals are symptomatic and receive treatment.

PMID- 22972118
TI  - Total disc replacement for chronic back pain in the presence of disc
      degeneration.
AB  - BACKGROUND: In the search for better surgical treatment of chronic low-back pain
      (LBP) in the presence of disc degeneration, total disc replacement has received
      increasing attention in recent years. A possible advantage of total disc
      replacement compared with fusion is maintained mobility at the operated level,
      which has been suggested to reduce the chance of adjacent segment degeneration.
      OBJECTIVES: The aim of this systematic review was to assess the effect of total
      disc replacement for chronic low-back pain in the presence of lumbar disc
      degeneration compared with other treatment options in terms of patient-centred
      improvement, motion preservation and adjacent segment degeneration. SEARCH
      METHODS: A comprehensive search in Cochrane Back Review Group (CBRG) trials
      register, CENTRAL, MEDLINE, EMBASE, BIOSIS, ISI, and the FDA register was
      conducted. We also checked the reference lists and performed citation tracking of
      included studies. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs) comparing total disc replacement with any other intervention for
      degenerative disc disease. DATA COLLECTION AND ANALYSIS: We assessed risk of bias
      per study using the criteria of the CBRG. Quality of evidence was graded
      according to the GRADE approach. Two review authors independently selected
      studies and assessed risk of bias of the studies. Results and upper bounds of
      confidence intervals were compared against predefined clinically relevant
      differences. MAIN RESULTS: We included 40 publications, describing seven unique
      RCT's. The follow-up of the studies was 24 months, with only one extended to five
      years. Five studies had a low risk of bias, although there is a risk of bias in
      the included studies due to sponsoring and absence of any kind of blinding. One
      study compared disc replacement against rehabilitation and found a statistically
      significant advantage in favour of surgery, which, however, did not reach the
      predefined threshold for clinical relevance. Six studies compared disc
      replacement against fusion and found that the mean improvement in VAS back pain
      was 5.2 mm (of 100 mm) higher (two studies, 676 patients; 95% confidence interval
      (CI) 0.18 to 10.26) with a low quality of evidence while from the same studies
      leg pain showed no difference. The improvement of Oswestry score at 24 months in
      the disc replacement group was 4.27 points more than in the fusion group (five
      studies; 1207 patients; 95% CI 1.85 to 6.68) with a low quality of evidence. Both
      upper bounds of the confidence intervals for VAS back pain and Oswestry score
      were below the predefined clinically relevant difference. Choice of control group
      (circumferential or anterior fusion) did not appear to result in different
      outcomes. AUTHORS' CONCLUSIONS: Although statistically significant, the
      differences between disc replacement and conventional fusion surgery for
      degenerative disc disease were not beyond the generally accepted clinical
      important differences with respect to short-term pain relief, disability and
      Quality of Life. Moreover, these analyses only represent a highly selected
      population. The primary goal of prevention of adjacent level disease and facet
      joint degeneration by using total disc replacement, as noted by the manufacturers
      and distributors, was not properly assessed and not a research question at all.
      Unfortunately, evidence from observational studies could not be used because of
      the high risk of bias, while these could have improved external validity
      assessment of complications in less selected patient groups. Non-randomised
      studies should however be very clear about patient selection and should
      incorporate independent, blinded outcome assessment, which was not the case in
      the excluded studies. Therefore, because we believe that harm and complications
      may occur after years, we believe that the spine surgery community should be
      prudent about adopting this technology on a large scale, despite the fact that
      total disc replacement seems to be effective in treating low-back pain in
      selected patients, and in the short term is at least equivalent to fusion
      surgery.

PMID- 22972119
TI  - Endothelin receptor antagonists for subarachnoid hemorrhage.
AB  - BACKGROUND: A subarachnoid hemorrhage (SAH) is a serious and potentially life
      threatening condition where blood leaks out of blood vessels over the surface of
      the brain. Delayed ischemic neurological deficit (DIND) and the related feature
      of vasospasm, where patients experience a delayed deterioration, have long been
      recognized as the leading potentially treatable cause of death and disability in
      patients with SAH. Endothelin is a potent, long-lasting endogenous
      vasoconstrictor that has been implicated in the pathogenesis of DIND. Therefore,
      endothelin receptor antagonists (ETAs) have emerged as a promising therapeutic
      option for SAH-induced cerebral vasospasm. OBJECTIVES: To assess the efficacy and
      tolerability of ETAs for SAH. SEARCH METHODS: We searched the Cochrane Stroke
      Group Trials Register (December 2011), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 11), MEDLINE (1950
      to December 2011), EMBASE (1946 to December 2011) and the Chinese Biomedical
      Database (1978 to December 2011). In an effort to identify further published,
      unpublished and ongoing trials we searched additional Chinese databases, ongoing
      trials registers, Google Scholar and Medical Matrix, handsearched journals,
      scanned reference lists, and contacted researchers and pharmaceutical companies.
      SELECTION CRITERIA: We only included randomized controlled trials (RCTs) that
      compared an ETA with placebo for SAH in adult (18 years of age or older) patients
      who met the diagnostic criteria for SAH based on clinical symptoms, with
      confirmation on computerized tomography scan results or angiography. Two review
      authors independently selected RCTs according to the inclusion criteria. We
      resolved disagreements by discussion with a third review author. DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected relevant articles and
      assessed their eligibility according to the inclusion and exclusion criteria. We
      resolved disagreements by discussion with a third review author. We used the
      random-effects model and expressed the results as risk ratio (RR) for dichotomous
      outcomes and mean difference (MD) for continuous outcomes with 95% confidence
      intervals (CI). MAIN RESULTS: We included four RCTs with 2024 participants that
      compared ETAs with placebo for SAH. All RCTs were multicenter, double-blind
      studies with a low risk of bias. ETAs reduced the incidence of DIND (RR 0.80; 95%
      CI 0.67 to 0.95) and angiographic vasospasm (RR 0.62; 95% CI 0.52 to 0.72) but
      did not reduce the incidence of unfavorable outcomes (RR 0.87; 95% CI 0.74 to
      1.02) or mortality (RR 1.05; 95% CI 0.77 to 1.45). ETAs increased the incidence
      of hypotension (RR 2.53; 95% CI 1.77 to 3.62) and pneumonia (RR 1.56; 95% CI 1.23
      to 1.97). AUTHORS' CONCLUSIONS: ETAs appear to reduce DIND and angiographic
      vasospasm but there were adverse events and the impact on clinical outcome is
      unclear. Additional well-designed RCTs are needed.

PMID- 22972120
TI  - Preoperative analgesics for additional pain relief in children and adolescents
      having dental treatment.
AB  - BACKGROUND: Fear of dental pain is a major barrier to children needing dental
      care. The use of preoperative analgesics has the potential to reduce
      postoperative discomfort. In addition it might also reduce intraoperative pain.
      Reviewing the available evidence will determine whether further research is
      warranted and will inform the development of prescribing guidelines. OBJECTIVES:
      To assess the effects of preoperative analgesics for pain relief in children and
      adolescents undergoing dental treatment. SEARCH METHODS: We searched the
      following electronic databases: the Cochrane Oral Health Group Trials Register
      (to 8 March 2012), the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2012, Issue 1), MEDLINE via OVID (1950 to 8 March 2012),
      EMBASE via OVID (1980 to 8 March 2012), LILACS via BIREME (1982 to 8 March 2012)
      and the ISI Web of Knowledge (1945 to 8 March 2012). There were no restrictions
      regarding language or date of publication.The reference lists of all eligible
      trials were checked for additional studies. Specialists in the field were
      contacted for any unpublished data. SELECTION CRITERIA: Randomised controlled
      clinical trials of analgesics given before dental treatment versus placebo or no
      analgesics in children and adolescents aged up to 17 years. We excluded children
      and adolescents having dental treatment under sedation (including nitrous
      oxide/oxygen) or general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review
      authors assessed titles and abstracts for eligibility and undertook data
      extraction and assessment of risk of bias. MAIN RESULTS: Five trials met the
      review's inclusion criteria with 190 participants in total. Three trials were
      dentally related i.e. restorative and extraction treatments; two trials related
      to orthodontic treatment. None of the included trials were judged to be at low
      risk of bias. Three trials compared paracetamol with placebo, only two of which
      provided data for analysis (presence or absence of parent-reported postoperative
      pain behaviour). The meta-analysis of the two trials showed a nonsignificant risk
      ratio (RR) for postoperative pain-related behaviours of 0.81 (95% confidence
      interval (CI) 0.53 to 1.22; P = 0.31), which showed no evidence of a benefit in
      taking paracetamol preoperatively (52% reporting pain in placebo versus 42% in
      test group). One of these trials was at unclear risk of bias, the other at high
      risk. Four trials compared ibuprofen with placebo. Three of these trials provided
      useable data. One trial reported no statistical difference in postoperative pain
      experienced by the ibuprofen group and the control group for children undergoing
      dental treatment. Data from two trials, including patients who were having
      orthodontic separator replacement without a general anaesthetic, were pooled to
      determine the effect of preoperative ibuprofen on the severity of postoperative
      pain. There was a statistically significant benefit, with regard to severity of
      postoperative pain, for giving ibuprofen preoperatively with mean difference 
      19.12 (95% CI -29.36 to -8.87; P = 0.0003; moderate quality evidence) on a visual
      analogue scale (0 to 100) indicating a probable benefit for preoperative
      ibuprofen before this orthodontic procedure. However, both these trials were at
      high risk of bias. Adverse events were only reported in one trial (one patient
      from the ibuprofen group and one from the placebo group reporting a lip or cheek
      biting injury). AUTHORS' CONCLUSIONS: From the available evidence we cannot
      determine whether or not preoperative analgesics are of benefit in paediatric
      dentistry for procedures under local anaesthetic. There is probably a benefit in
      prescribing preoperative analgesics prior to orthodontic separator placement.

PMID- 22972121
TI  - Acupuncture for mumps in children.
AB  - BACKGROUND: Mumps is an acute, viral illness transmitted by respiratory droplets
      and saliva. A number of studies published in China have suggested that
      acupuncture is beneficial for children with mumps but the literature reporting
      the benefits or harms of acupuncture for mumps has not been systematically
      reviewed. OBJECTIVES: To determine the efficacy and safety of acupuncture for
      children with mumps. SEARCH METHODS: We searched CENTRAL (2012, Issue 4), MEDLINE
      (1950 to April week 4, 2012), EMBASE (1974 to May 2012), CINAHL (1981 to May
      2012), AMED (1985 to May 2012), the Chinese BioMedicine Database (CBM) (1979 to
      May 2012), China National Knowledge Infrastructure (CNKI) (1979 to May 2012),
      Chinese Technology Periodical Database (CTPD) (1989 to May 2012) and WANFANG
      database (1982 to May 2012). We also handsearched a number of journals (from
      first issue to current issue). SELECTION CRITERIA: We included randomised
      controlled trials comparing acupuncture with placebo acupuncture, no management,
      Chinese medication, Western medication or other treatments for mumps. Acupuncture
      included either traditional acupuncture or contemporary acupuncture, regardless
      of the source of stimulation (body, electro, scalp, fire, hand, fine needle,
      moxibustion). DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data and assessed the quality of included studies. We calculated risk
      ratios (RR) with their 95% confidence intervals (CI) for the effective percentage
      and standardised mean differences (SMD) with 95% CIs for the time to cure. MAIN
      RESULTS: Only one study with 239 participants met our inclusion criteria. There
      were a total of 120 participants in the acupuncture group, of which 106
      recovered, with their temperature returning back to normal and no swelling or
      pain of the parotid gland; the condition of 14 participants improved, with a drop
      in temperature and alleviation of swelling or pain of the parotid gland. There
      were 119 participants in the Western medicine group, of which 56 recovered and
      the condition of 63 improved. The acupuncture group had a higher recovery rate
      than the control group. The relative RR of recovery was 1.88 (95% CI 1.53 to
      2.30). However, the acupuncture group had a longer time to cure than the control
      group. The mean was 4.20 days and the standard deviation (SD) was 0.46 in the
      acupuncture group, while in the control group the mean was 3.78 days and the SD
      was 0.46.There was a potential risk of bias in the study because of low
      methodological quality. AUTHORS' CONCLUSIONS: We could not reach any confident
      conclusions about the efficacy and safety of acupuncture based on one study. More
      high-quality research is needed.

PMID- 22972122
TI  - Extended peginterferon plus ribavirin treatment for 72 weeks versus standard
      peginterferon plus ribavirin treatment for 48 weeks in chronic hepatitis C
      genotype 1 infected slow-responder adult patients.
AB  - BACKGROUND: The standard length of peginterferon plus ribavirin treatment for
      chronic hepatitis C virus (HCV) genotype 1 infected patients is 48 weeks.
      However, the number of patients demonstrating a sustained virological response is
      not high. In order to improve sustained virological response, extending the
      length of the treatment period has been suggested. OBJECTIVES: To study the
      benefits and harms of extended 72-week treatment in comparison with 48-week
      treatment with peginterferon plus ribavirin in patients with chronic HCV genotype
      1 infection who have shown a slow antiviral response. SEARCH METHODS: We searched
      the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE,
      Science Citation Index Expanded, and LILACS until November 2011. We identified
      further trials by reviewing reference lists and contacting principal authors.
      SELECTION CRITERIA: Trials were eligible for this review if they included
      patients infected with hepatitis C virus genotype 1 who had a slow antiviral
      response, and if those patients were randomised to completing 72 weeks versus 48
      weeks of treatment with pegylated interferon and ribavirin. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the trials for risk of bias, and
      extracted the data. The primary outcomes were overall mortality, liver-related
      mortality, and liver-related morbidity. We extracted data separately according to
      two definitions of slow responders: 1) patients with >= 2 log viral reduction but
      still detectable HCV RNA after 12 weeks of treatment and undetectable HCV RNA
      after 24 weeks of treatment; 2) patients with detectable HCV RNA after four weeks
      of treatment. We calculated risk ratios from individual trials as well as in the
      meta-analyses of trials. MAIN RESULTS: We included seven trials with 1369
      participants. All trials had high risk of bias. Five trials used our first
      definition of slow responders, and three other trials (including one that used
      both definitions) used the second definition. None of the included trials
      mentioned our primary outcomes. However, regarding the secondary outcomes,
      extension of the treatment period to 72 weeks increased the sustained virological
      response according to both definitions (71/217 (32.7%) versus 52/194 (26.8%);
      risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92, P = 0.02, I(2) =
      8%; and 265/499 (53.1%) versus 207/496 (41.7%); RR 1.27, 95% CI 1.07 to 1.50, P =
      0.006, I(2) = 38%), with a risk difference of 0.11 and calculated number needed
      to treat of nine. The end of treatment response was not significantly different
      between the two treatment groups. The number of participants who relapsed
      virologically was found to be lower in the groups that had been treated for 72
      weeks using both definitions (27/84 (32.1%) versus 46/91 (50.5%); RR 0.59, 95% CI
      0.40 to 0.86, P = 0.007, I(2) = 18%, 3 trials; and 85/350 (24.3%) versus 146/353
      (41.4%); RR 0.59, 95% CI 0.47, 0.73, P < 0.000001, I(2) = 0%, 3 trials). The
      length of treatment did not significantly affect the adherence (247/279 (88.5%)
      versus 252/274 (92.0%); RR 0.95, 95% CI 0.84 to 1.07, P = 0.42, I(2) = 69%, 3
      trials). In the single trial that reported adverse events, no significant
      difference was seen between the two treatment groups. AUTHORS' CONCLUSIONS: This
      review demonstrates higher a proportion of sustained virological response after
      extension of treatment from 48 weeks to 72 weeks in HCV genotype 1 infected
      patients in whom HCV RNA was still detectable but decreased by >= 2 log after 12
      weeks and became negative after 24 weeks of treatment, and in patients with
      detectable HCV RNA after four weeks of treatment with peginterferon plus
      ribavirin. The observed intervention effects can be caused by both systematic
      error (bias) and random errors (play of chance). There was no reporting on
      mortality and the reporting of clinical outcomes and adverse events was
      insufficient. More data are needed in order to recommend or reject the policy of
      extending the treatment period for slow responders.

PMID- 22972123
TI  - Atypical antipsychotics for disruptive behaviour disorders in children and
      youths.
AB  - BACKGROUND: Disruptive behaviour disorders include conduct disorder, oppositional
      defiant disorder and disruptive behaviour not otherwise specified. Attention
      deficit hyperactivity disorder (ADHD) is frequently associated with disruptive
      behaviour disorders. The difficulties associated with disruptive behaviour
      disorders are demonstrated through aggression and severe behavioural problems.
      These often result in presentation to psychiatric services and may be treated
      with medications such as atypical antipsychotics. There is increasing evidence of
      a significant rise in the use of atypical antipsychotics for treating disruptive
      behaviour disorders in child and adolescent populations. OBJECTIVES: To evaluate
      the effect and safety of atypical antipsychotics, compared to placebo, for
      treating disruptive behaviour disorders in children and youths.  SEARCH METHODS:
      We searched the following databases in August 2011: CENTRAL (2011, Issue 3),
      MEDLINE (1948 to August Week 1), EMBASE (1980 to 2011 Week 32), PsycINFO (1806 to
      August Week 2 2011), CINAHL (1937 to current), ClinicalTrials.gov (searched 15
      August 2011), Australian New Zealand Clinical Trials Registry (ANZCTR) (searched
      15 August 2011), CenterWatch (searched 15 August 2011) and ICTRP (searched 15
      August 2011). SELECTION CRITERIA: We included randomised controlled trials with
      children and youths up to and including the age of 18, in any setting, with a
      diagnosis of a disruptive behaviour disorder. We included trials where
      participants had a comorbid diagnosis of attention deficit hyperactivity
      disorder, major depression or an anxiety disorder. DATA COLLECTION AND ANALYSIS:
      Two review authors independently selected the studies and disagreements were
      resolved by discussion. Two review authors extracted data independently. One
      review author entered data into Review Manager software and another checked it.
      We contacted trial authors for information about adverse effects and to provide
      missing data. MAIN RESULTS: We included eight randomised controlled trials,
      spanning 2000 to 2008. Seven assessed risperidone and one assessed quetiapine.
      Three of the studies were multicentre. Seven trials assessed acute efficacy and
      one assessed time to symptom recurrence over a six-month maintenance period.We
      performed meta-analyses for the primary outcomes of aggression, conduct problems
      and weight changes but these were limited by the available data as different
      trials reported either mean change scores (average difference) or final/post
      intervention raw scores and used different outcome measures. We also evaluated
      each individual trial's treatment effect size where possible, using Hedges' g.For
      aggression, we conducted two meta-analyses. The first included three trials
      (combined n = 238) using mean difference (MD) on the Aberrant Behaviour Checklist
      (ABC) Irritability subscale. Results yielded a final mean score with treatment
      that was 6.49 points lower than the post-intervention mean score with placebo
      (95% confidence interval (CI) -8.79 to -4.19). The second meta-analysis on
      aggression included two trials (combined n = 57) that employed two different
      outcome measures (Overt Aggression Scale (modified) (OAS-M) and OAS,
      respectively) and thus we used a standardised mean difference. Results yielded an
      effect estimate of -0.18 (95% CI -0.70 to 0.34), which was statistically non
      significant.We also performed two meta-analyses for conduct problems. The first
      included two trials (combined n = 225), both of which employed the Nisonger Child
      Behaviour Rating Form - Conduct Problem subscale (NCBRF-CP). The results yielded
      a final mean score with treatment that was 8.61 points lower than that with
      placebo (95% CI -11.49 to -5.74). The second meta-analysis on conduct problems
      included two trials (combined n = 36), which used the Conners' Parent Rating
      Scale - Conduct Problem subscale (CPRS-CP). Results yielded a mean score with
      treatment of 12.67 lower than with placebo (95% CI -37.45 to 12.11), which was a
      statistically non-significant result.With respect to the side effect of weight
      gain, a meta-analysis of two studies (combined n = 138) showed that participants
      on risperidone gained on average 2.37 kilograms more than those in the placebo
      group over the treatment period (MD 2.37; 95% CI 0.26 to 4.49).For individual
      trials, there was a range of effect sizes (ranging from small to large) for
      risperidone reducing aggression and conduct problems. The precision of the
      estimate of the effect size varied between trials. AUTHORS' CONCLUSIONS: There is
      some limited evidence of efficacy of risperidone reducing aggression and conduct
      problems in children aged 5 to 18 with disruptive behaviour disorders in the
      short term.For aggression, the difference in scores of 6.49 points on the ABC
      Irritability subscale (range 0 to 45) may be clinically significant. For conduct
      problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48)
      is likely to be clinically significant.Caution is required due to the limitations
      of the evidence and the small number of relevant high-quality studies. The
      findings from the one study assessing impact in the longer term suggest that the
      effects are maintained to some extent (small effect size) for up to six months.
      Inadequately powered studies produced non-significant results. The evidence is
      restricted by heterogeneity of the population (including below average and
      borderline IQ), and methodological issues in some studies, such as use of
      enriched designs and risk of selection bias. No study addressed the issue of pre
      existing/concurrent psychosocial interventions, and comorbid stimulant medication
      and its dosage was only partially addressed. There is currently no evidence to
      support the use of quetiapine for disruptive behaviour disorders in children and
      adolescents.It is uncertain to what degree the efficacy found in clinical trials
      will translate into real life clinical practice. Participants in the studies were
      recruited from clinical services but those who agree to take part in the clinical
      trials are a subset of the overall population presenting for care. There are no
      research data for children under five years of age. Further high-quality research
      is required with large samples of clinically representative youths and long-term
      follow-up to replicate current findings.

PMID- 22972124
TI  - Chinese medicinal herbs for mumps.
AB  - BACKGROUND: Mumps is an infectious disease caused by the mumps virus. Chinese
      physicians generally believe that Chinese medicinal herbs are effective in
      alleviating symptoms and reducing the duration of mumps. Herbalists tend to
      develop a treatment plan according to the individual's symptoms. OBJECTIVES: To
      evaluate the effectiveness and safety of Chinese medicinal herbs for mumps.
      SEARCH METHODS: We searched CENTRAL Issue 4, 2012, MEDLINE (1948 to April week 3,
      2012), EMBASE (1974 to April 2012), CINAHL (1981 to April 2012), AMED (1985 to
      April 2012), the Chinese Biomedical Database (CBM) (1980 to May 2012), China
      National Knowledge Infrastructure (CNKI) (1979 to May 2012), VIP Information
      (1989 to May 2012), and relevant databases of ongoing trials. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of Chinese medicinal herbs for mumps (with or
      without complications). DATA COLLECTION AND ANALYSIS: Two review authors (MS, ZL)
      independently evaluated trial quality and conducted data extraction. We contacted
      the trial authors for missing data regarding participant allocation. Some trials
      allocated participants according to the participants' admitting sequence, making
      it a pseudo-random allocation. None of the trials concealed participants
      allocation or used blinding. MAIN RESULTS: We did not identify any eligible
      trials for inclusion. We identified 102 studies which claimed to use random
      allocation. Ninety-nine studies were excluded because the allocation methods the
      authors had used were not actually randomised. We were unable to contact the
      trial authors of the remaining three studies. These trials require further
      evaluation and have been allocated to the 'Studies awaiting classification'
      section. AUTHORS' CONCLUSIONS: We did not find any RCTs for or against Chinese
      herbal medicine used in the treatment of mumps. We hope more high-quality RCTs
      will be conducted in the future.

PMID- 22972125
TI  - Chlorambucil for patients with primary biliary cirrhosis.
AB  - BACKGROUND: Chlorambucil has been used for patients with primary biliary
      cirrhosis as it possesses immunosuppressive properties. But it is unknown whether
      it benefits or harms these patients. OBJECTIVES: To evaluate the beneficial and
      any harmful effects of chlorambucil for primary biliary cirrhosis patients.
      SEARCH METHODS: Eligible trials were identified by searching the Cochrane Hepato
      Biliary Group Controlled Trials Register (March 2012), the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012, Issue 2),
      MEDLINE (1946 to March 2012), EMBASE (1974 to March 2012), Science Citation Index
      EXPANDED (1900 to March 2012), The Chinese Biomedical Database (1976 to March
      2012), The Chinese Medical Current Contents (1994 to March 2012), The China
      Hospital Knowledge Database (1994 to March 2012), and a database of ongoing
      trials (http://www.controlled-trials.com/mrct/) (accessed 6 March 2012). The
      reference lists of the retrieved publications and review articles were also read
      through, and pharmaceutical companies known to produce chlorambucil were
      contacted. SELECTION CRITERIA: Randomised clinical trials, irrespective of
      language, year of publication, and publication status, comparing chlorambucil at
      any dose versus placebo, no intervention, another active drug, or one dose of
      chlorambucil with another dose. DATA COLLECTION AND ANALYSIS: We planned to
      assess continuous data with mean differences (MD), and dichotomous outcomes with
      relative risk (RR), both with 95% confidence intervals (CI). As we only
      identified one trial, Fisher's exact tests were employed. MAIN RESULTS: Only one
      randomised trial was identified and included in the review. The bias risk in the
      trial was high. The trial compared chlorambucil versus no intervention in 24
      patients with primary biliary cirrhosis. Fisher's exact test did not show a
      significant reduction of mortality when comparing chlorambucil with no treatment
      (0/13 (0%) versus (2/11 (18.2%); P = 0.20). There was no significant difference
      regarding adverse events for chlorambucil compared with no treatment, but all
      patients receiving chlorambucil experienced adverse events (13/13 (100%) versus
      (3/11 (27%); P = 0.1). According to the authors of the trial, chlorambucil led to
      a significant improvement in mean serum levels of bilirubin (P < 0.05), albumin
      (P < 0.05), immunoglobulin M (P < 0.01), serum aspartate aminotransferase
      activity (P < 0.01), and hepatic inflammatory infiltrates (P < 0.01). AUTHORS'
      CONCLUSIONS: There is not sufficient evidence to support or reject the use of
      chlorambucil for patients with primary biliary cirrhosis. Chlorambucil may show
      benefit in some unvalidated surrogate outcome measures (for example, serum
      bilirubin and immunoglobulin M levels). Chlorambucil is, however, connected with
      a number of adverse events. Bone marrow suppression should be noted in
      particular. Further randomised clinical trials are necessary to assess the
      benefits and harms of chlorambucil in this indication.

PMID- 22972126
TI  - Pneumococcal vaccines for cystic fibrosis.
AB  - BACKGROUND: Invasive pneumococcal disease is associated with significant
      mortality and many countries have introduced routine pneumococcal vaccination
      into their childhood immunisation programmes. Whilst pneumococcal disease in
      cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection
      against pulmonary exacerbations caused by this pathogen. In the USA and UK
      pneumococcal vaccination is currently recommended for all children and adults
      with cystic fibrosis. OBJECTIVES: To assess the efficacy of pneumococcal vaccines
      in reducing morbidity in people with cystic fibrosis. SEARCH METHODS: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials
      Register, which comprises references identified from comprehensive electronic
      database searches and handsearches of relevant journals and abstract books of
      conference proceedings. In addition, the pharmaceutical manufacturers of the
      polysaccharide and conjugate pneumococcal vaccines were approached.Date of the
      most recent search: 10 July 2012. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials comparing pneumococcal vaccination (with either a
      polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo
      in children or adults with cystic fibrosis were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: There
      are no trials included in this review. AUTHORS' CONCLUSIONS: As no trials were
      identified we cannot draw conclusions on the efficacy of routine pneumococcal
      immunisation in people with cystic fibrosis in reducing their morbidity or
      mortality. As many countries now include pneumococcal immunisation in their
      routine childhood vaccination schedule it is unlikely that future randomised
      controlled trials will be initiated. Rigorously conducted epidemiological studies
      may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in
      reducing morbidity and mortality in people with cystic fibrosis.

PMID- 22972127
TI  - Spinal manipulative therapy for acute low-back pain.
AB  - BACKGROUND: Many therapies exist for the treatment of low-back pain including
      spinal manipulative therapy (SMT), which is a worldwide, extensively practised
      intervention. This report is an update of the earlier Cochrane review, first
      published in January 2004 with the last search for studies up to January 2000.
      OBJECTIVES: To examine the effects of SMT for acute low-back pain, which is
      defined as pain of less than six weeks duration. SEARCH METHODS: A comprehensive
      search was conducted on 31 March 2011 in the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PEDro, and the Index to
      Chiropractic Literature. Other search strategies were employed for completeness.
      No limitations were placed on language or publication status. SELECTION CRITERIA:
      Randomized controlled trials (RCTs) which examined the effectiveness of spinal
      manipulation or mobilization in adults with acute low-back pain were included. In
      addition, studies were included if the pain was predominantly in the lower back
      but the study allowed mixed populations, including participants with radiation of
      pain into the buttocks and legs. Studies which exclusively evaluated sciatica
      were excluded. No other restrictions were placed on the setting nor the type of
      pain. The primary outcomes were back pain, back-pain specific functional status,
      and perceived recovery. Secondary outcomes were return-to-work and quality of
      life. SMT was defined as any hands-on therapy directed towards the spine, which
      includes both manipulation and mobilization, and includes studies from
      chiropractors, manual therapists, and osteopaths. DATA COLLECTION AND ANALYSIS:
      Two review authors independently conducted the study selection and risk of bias
      (RoB) assessment. Data extraction was checked by the second review author. The
      effects were examined in the following comparisons: SMT versus 1) inert
      interventions, 2) sham SMT, 3) other interventions, and 4) SMT as an additional
      therapy. In addition, we examined the effects of different SMT techniques
      compared to one another. GRADE was used to assess the quality of the evidence.
      Authors were contacted, where possible, for missing or unclear data. Outcomes
      were evaluated at the following time intervals: short-term (one week and one
      month), intermediate (three to six months), and long-term (12 months or longer).
      Clinical relevance was defined as: 1) small, mean difference (MD) < 10% of the
      scale or standardized mean difference (SMD) < 0.4; 2) medium, MD = 10% to 20% of
      the scale or SMD = 0.41 to 0.7; and 3) large, MD > 20% of the scale or SMD > 0.7.
      MAIN RESULTS: We identified 20 RCTs (total number of participants = 2674), 12
      (60%) of which were not included in the previous review. Sample sizes ranged from
      36 to 323 (median (IQR) = 108 (61 to 189)). In total, six trials (30% of all
      included studies) had a low RoB. At most, three RCTs could be identified per
      comparison, outcome, and time interval; therefore, the amount of data should not
      be considered robust. In general, for the primary outcomes, there is low to very
      low quality evidence suggesting no difference in effect for SMT when compared to
      inert interventions, sham SMT, or when added to another intervention. There was
      varying quality of evidence (from very low to moderate) suggesting no difference
      in effect for SMT when compared with other interventions, with the exception of
      low quality evidence from one trial demonstrating a significant and moderately
      clinically relevant short-term effect of SMT on pain relief when compared to
      inert interventions, as well as low quality evidence demonstrating a significant
      short-term and moderately clinically relevant effect of SMT on functional status
      when added to another intervention. In general, side-lying and supine thrust SMT
      techniques demonstrate a short-term significant difference when compared to non
      thrust SMT techniques for the outcomes of pain, functional status, and recovery.
      AUTHORS' CONCLUSIONS: SMT is no more effective in participants with acute low
      back pain than inert interventions, sham SMT, or when added to another
      intervention. SMT also appears to be no better than other recommended therapies.
      Our evaluation is limited by the small number of studies per comparison, outcome,
      and time interval. Therefore, future research is likely to have an important
      impact on these estimates. The decision to refer patients for SMT should be based
      upon costs, preferences of the patients and providers, and relative safety of SMT
      compared to other treatment options. Future RCTs should examine specific
      subgroups and include an economic evaluation.

PMID- 22972128
TI  - Interventions for mycosis fungoides.
AB  - BACKGROUND: Mycosis fungoides is the most common type of cutaneous T-cell
      lymphoma, a malignant, chronic disease initially affecting the skin. Several
      therapies are available, which may induce clinical remission for a time.
      OBJECTIVES: To assess the effects of interventions for mycosis fungoides in all
      stages of the disease. SEARCH METHODS: We searched the following databases up to
      January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The
      Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from
      1982). We also checked reference lists of included studies for further references
      to relevant RCTs. We searched online trials registries for further references to
      unpublished trials and undertook a separate search for adverse effects of
      interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of interventions for mycosis
      fungoides in people with any stage of the disease. At least 90% of participants
      in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin
      type). DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      eligibility and methodological quality for each study and carried out data
      extraction. We resolved any disagreement by discussion. Primary outcomes were the
      impact on quality of life and the safety of interventions. When available, we
      reported on our secondary outcomes, which were the improvement or clearance of
      skin lesions, disease-free intervals, survival rates, relapse rates, and rare
      adverse effects. When possible, we combined homogeneous studies for meta
      analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the
      internal validity of all included studies in six different domains. MAIN RESULTS:
      The review included 14 RCTs involving 675 participants, covering a wide range of
      interventions. Eleven of the included trials assessed participants in clinical
      stages IA to IIB only (please see Table 1 for definitions of these
      stages).Internal validity was considerably low in studies with a high or unclear
      risk of bias. The main reasons for this were low methodological quality or
      missing data, even after we contacted the study authors, and a mean dropout rate
      of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a
      maximum of 103 participants. Only one study provided a long enough follow-up for
      reliable survival analysis.Included studies assessed topical treatments, such as
      imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional
      injections of interferon-alpha (IFN-alpha). The light therapies investigated
      included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis
      (photochemotherapy), and visible light. Oral treatments included acitretin,
      bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted
      of denileukin diftitox; a combination of chemotherapy and electron beam
      radiation; and intramuscular injections of active transfer factor. Nine studies
      evaluated therapies by using an active comparator; five were placebo-controlled
      RCTs.Twelve studies reported on common adverse effects, while only two assessed
      quality of life. None of these studies compared the health-related quality of
      life of participants undergoing different treatments. Most of the reported
      adverse effects were attributed to the interventions. Systemic treatments, and
      here in particular a combined therapeutic regimen of chemotherapy and electron
      beam, bexarotene, or denileukin diftitox, showed more adverse effects than
      topical or skin-directed treatments.In the included studies, clearance rates
      ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis
      combining the results of 2 trials comparing the effect of IFN-alpha and PUVA
      versus PUVA alone showed no significant difference in the relative risk of
      clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included
      studies demonstrated a significant increase in disease-free intervals, relapse,
      or overall survival. AUTHORS' CONCLUSIONS: This review identified trial evidence
      for a range of different topical and systemic interventions for mycosis
      fungoides. Because of substantial heterogeneity in design, small sample sizes,
      and low methodological quality, the comparative safety and efficacy of these
      interventions cannot be established on the basis of the included RCTs. Taking
      into account the possible serious adverse effects and the limited availability of
      efficacy data, topical and skin-directed treatments are recommended first,
      especially in the early stages of disease. More aggressive therapeutic regimens
      may show improvement or clearance of lesions, but they also result in more
      adverse effects; therefore, they are to be considered with caution. Larger
      studies with comparable, clearly-defined end points for all stages of mycosis
      fungoides, and a focus on safety, quality of life, and duration of remission as
      part of the outcome measures, are necessary.

PMID- 22972129
TI  - Irrigants for non-surgical root canal treatment in mature permanent teeth.
AB  - BACKGROUND: Root canal treatment is carried out on teeth in which irreversible
      pulpitis has led to necrosis of the dental pulp. As a treatment option it is an
      alternative to dental extraction. Mechanical preparation and irrigation with
      antiseptic or antibacterial solutions destroys bacteria and cleans the infected
      root canal. Irrigants should be effective in deactivating bacteria in the entire
      root canal space without causing any adverse tissue reactions. Sodium
      hypochlorite (NaOCl) and chlorhexidine are commonly used but there is uncertainty
      as to which solution, concentration or combination is the most effective.
      OBJECTIVES: To assess the effects of irrigants used in the non-surgical root
      canal treatment of mature permanent teeth. SEARCH METHODS: We searched the
      Cochrane Oral Health Group's Trials Register (to 5 July 2012), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      4), MEDLINE via Ovid (1950 to 5 July 2012), EMBASE via Ovid (1980 to 5 July
      2012), LILACS via BIREME (1980 to 5 July 2012). There were no restrictions
      regarding language or date of publication. SELECTION CRITERIA: Randomised
      controlled trials in single or multi-rooted permanent teeth with pulpal or
      periapical pathology or both, which require root canal treatment. Irrigants
      either against each other or against inactive irrigant or placebo. Combinations
      of irrigants were allowed and if used in conjunction with EDTA
      (ethylenediaminetetra-acetic acid) or similar chelating agents. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed risk of bias of included
      trials and extracted data. MAIN RESULTS: We included 11 trials involving 851
      participants with 879 teeth which had undergone root canal treatment and involved
      the use of irrigants. Two trials were assessed as being at low risk of bias, with
      six unclear and three high. Four trials compared sodium hypochlorite versus
      chlorhexidine, however, no primary outcomes and only one secondary outcome,
      bacterial growth cultures, was reported for two of these trials (20% and 50% of
      teeth in the control group had positive bacterial culture). The meta-analysis
      indicated no strong evidence of a difference in the existence of bacterial growth
      between the interventions (risk ratio 0.73; 95% confidence interval 0.34 to 1.56;
      P = 0.41). The seven remaining trials each compared different interventions and
      only two of these trials included useable data on the primary outcomes of
      swelling and pain. One trial compared sodium hypochlorite 5.25% alone versus
      sodium hypochlorite 5.25% combined with hydrogen peroxide 3%, and versus normal
      saline and reported pain at 3 to 14 days after the procedure. There was no
      evidence of a difference in pain between the three groups. The other trial
      compared sodium hypochlorite 5% versus sodium hypochlorite with 'proteolytic
      enzyme', and there was no evidence of a difference in swelling between the
      groups. Two further trials reported bacterial growth, and three trials failed to
      report any data which could be used in the review. None of the included trials
      reported any data on adverse effects nor radiological changes in periapical
      radiolucency. AUTHORS' CONCLUSIONS: Although root canal irrigants such as sodium
      hypochlorite and chlorhexidine appear to be effective at reducing bacterial
      cultures when compared to saline, most of the studies included in this review
      failed to adequately report these clinically important and potentially patient
      relevant outcomes. There is currently insufficient reliable evidence showing the
      superiority of any one individual irrigant. The strength and reliability of the
      supporting evidence was variable and clinicians should be aware that changes in
      bacterial counts or pain in the early postoperative period may not be accurate
      indicators of long-term success. Future trials should report both clinician
      relevant and patient-preferred outcomes at clearly defined perioperative, as well
      as long-term, time points.

PMID- 22972130
TI  - Allergen-specific oral immunotherapy for peanut allergy.
AB  - BACKGROUND: Peanut allergy is one of the most common forms of food allergy
      encountered in clinical practice.  In most cases, it does not spontaneously
      resolve; furthermore, it is frequently implicated in acute life-threatening
      reactions. The current management of peanut allergy centres on meticulous
      avoidance of peanuts and peanut-containing foods. Allergen-specific oral
      immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then
      tolerance to peanut, and has the potential to revolutionise the management of
      peanut allergy. However, at present there is still considerable uncertainty about
      the effectiveness and safety of this approach. OBJECTIVES: To establish the
      effectiveness and safety of OIT in people with IgE-mediated peanut allergy who
      develop symptoms after peanut ingestion. SEARCH METHODS: We searched in the
      following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE,
      Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE,
      PakMediNet and TRIP. We also searched registers of on-going and unpublished
      trials. The date of the most recent search was January 2012. SELECTION CRITERIA:
      Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials
      involving children or adults with clinical features indicative of IgE-mediated
      peanut allergy treated with allergen-specific OIT, compared with control group
      receiving either placebo or no treatment, were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: Two review authors independently checked and reviewed
      titles and abstracts of identified studies and assessed risk of bias. The full
      text of potentially relevant trials was assessed. Data extraction was
      independently performed by two reviewers with disagreements resolved through
      discussion. MAIN RESULTS: We found one small RCT, judged to be at low risk of
      bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation
      to peanut and a clinical history of reaction to peanut within 60 minutes of
      exposure. The study did not include children who had moderate to severe asthma or
      who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio
      resulting in 19 children being randomised to the intervention arm and nine to the
      placebo arm. Intervention arm children received OIT with peanut flour and control
      arm participants received placebo comprising of oat flour. The primary outcome
      was assessed using a double-blind, placebo controlled oral food challenge (OFC)
      at approximately one year. No data were available on longer term outcomes beyond
      the OFC conducted at the end of the study.Because of adverse events, three
      patients withdrew from the intervention arm before the completion of the study.
      Therefore, only 16 participants received the full course of peanut OIT, whereas
      all nine patients receiving placebo completed the trial. The per-protocol
      analysis found a significant increase in the threshold dose of peanut allergen
      required to trigger a reaction in those in the intervention arm with all 16
      participants able to ingest the maximum cumulative dose of 5000 mg of peanut
      protein (which the authors equate as being equivalent to approximately 20
      peanuts) without developing symptoms, whereas in the placebo group they were able
      to ingest a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001)
      before experiencing symptoms.  Per-protocol analyses also demonstrated that
      peanut OIT resulted in reductions in skin prick test size (P < 0.001),
      interleukin-5 (P = 0.01), interleukin-13 (P = 0.02) and an increase in peanut
      specific immunoglobulin G(4) (IgG(4)) (P < 0.01).Children in the intervention arm
      experienced more adverse events during treatment than those in the placebo arm.
      In the initial day escalation phase, nine (47%) of the 19 participants initially
      enrolled in the OIT arm experienced clinically-relevant adverse events which
      required treatment with H(1)-antihistamines, two of which required additional
      treatment with epinephrine (adrenaline). AUTHORS' CONCLUSIONS: The one small RCT
      we found showed that allergen-specific peanut OIT can result in desensitisation
      in children, and that this is associated with evidence of underlying immune
      modulation. However, this treatment approach was associated with a substantial
      risk of adverse events, although the majority of these were mild.  In view of the
      risk of adverse events and the lack of evidence of long-term benefits, allergen
      specific peanut OIT cannot currently be recommended as a treatment for the
      management of patients with IgE-mediated peanut allergy.  Larger RCTs are needed
      to investigate the acceptability, long-term effectiveness and cost-effectiveness
      of safer treatment regimens, particularly in relation to the induction of
      clinical and immunological tolerance.

PMID- 22972131
TI  - Bendamustine for patients with indolent B cell lymphoid malignancies including
      chronic lymphocytic leukaemia.
AB  - BACKGROUND: Indolent B cell lymphoid malignancies include follicular lymphoma,
      small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and
      marginal zone lymphomas. Chronic lymphocytic leukaemia (CLL) is a lymphoid
      malignancy similar to small lymphocytic lymphoma (SLL) in its leukaemic
      phase.Indolent lymphoid malignancies including CLL are characterised by slow
      growth, a high initial response rate and a relapsing and progressive disease
      course. Advanced-stage indolent B cell lymphoid malignancies are often incurable.
      If symptoms or progressive disease occur, chemotherapy plus rituximab is
      indicated. No chemotherapy regimen has been shown to improve overall survival
      compared to a different regimen.Bendamustine is efficacious in the treatment of
      patients with indolent B cell lymphoid malignancies. A number of randomised
      controlled trials have examined the effect of bendamustine compared to other
      chemotherapy regimens in these patients. Improved disease control with no
      survival benefit is shown. OBJECTIVES: To evaluate the efficacy of bendamustine
      therapy for patients with indolent B cell lymphoid malignancies including CLL.
      SEARCH METHODS: We electronically searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966
      to May 2012), EMBASE (1974 to November 2011), LILACS (1982 to May 2012),
      databases of ongoing trials (accessed 30 April 2012) and relevant conference
      proceedings. We searched references of identified trials and contacted the first
      author of each included trial. SELECTION CRITERIA: Randomised controlled trials
      that compared a bendamustine-containing regimen to other chemotherapy with or
      without immunotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently
      appraised the quality of each trial and extracted data from included trials. We
      estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence
      intervals (CI). MAIN RESULTS: We included five trials randomising 1343 adult
      patients in the systematic review. Allocation and blinding were unclear in three
      trials and adequate in two. Incomplete outcome data and selective reporting were
      adequate in all trials. Trials varied in the type of lymphoid malignancy,
      bendamustine regimen and the comparator regimen. In the three trials that
      included patients with follicular lymphoma, mantle cell lymphoma and other
      indolent lymphomas the comparator treatment was cyclophosphamide, a combination
      of cyclophosphamide, vincristine, doxorubicin and prednisone, and fludarabine.
      Two trials included only patients with CLL and compared bendamustine to
      chlorambucil, and to fludarabine. We did not conduct a meta-analysis due to the
      clinical heterogeneity among trials. Bendamustine had no statistically
      significant effect on the overall survival of patients with indolent B cell
      lymphoid malignancies in any of the included trials (trials of moderate quality).
      Progression-free survival was statistically significantly improved with
      bendamustine treatment compared to other chemotherapy in three of the four trials
      that reported on it. One trial demonstrated a non statistically significant
      improvement of PFS. The risk of grade 3 or 4 adverse events was similar when
      bendamustine was compared to CHOP and fludarabine, and higher when compared to
      chlorambucil. Compared to chlorambucil quality of life was unaffected by
      bendamustine treatment (one trial, no meta-analysis). AUTHORS' CONCLUSIONS: As
      none of the currently available chemotherapeutic protocols for induction therapy
      in indolent B cell lymphoid malignancies confer a survival benefit and due to the
      improved progression-free survival in each of the included trials, and a similar
      rate of grade 3 or 4 adverse events, bendamustine may be considered for the
      treatment of patients with indolent B cell lymphoid malignancies. However, the
      unclear effect on survival and the higher rate of adverse events compared to
      chlorambucil in patients with CLL/SLL does not support the use of bendamustine
      for these patients.The effect of bendamustine combined with rituximab should be
      evaluated in randomised clinical trials with more homogenous populations and
      outcomes for specific subgroups of patients by type of lymphoma should be
      reported. Any future trial should evaluate the effect of bendamustine on quality
      of life.

PMID- 22972132
TI  - Topical cyclosporine for atopic keratoconjunctivitis.
AB  - BACKGROUND: Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non
      infectious inflammatory condition that atopic dermatitis patients may suffer at
      any time point in the course of their dermatologic disease and is independent of
      its degree of severity. AKC is usually not self resolving and it poses a higher
      risk of corneal injuries and severe sequelae. Management of AKC should prevent or
      treat corneal damage. Although topical corticosteroids remain the standard
      treatment for patients with AKC, prolonged use may lead to complications. Topical
      cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a
      corticosteroid sparing agent. OBJECTIVES: To determine the efficacy and gather
      evidence on safety from randomised controlled trials (RCTs) of topical CsA in
      patients with AKC. SEARCH METHODS: We searched CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue
      6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012),
      Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982
      to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature
      in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal
      (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of
      Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use
      any date or language restrictions in the electronic searches for trials. The
      electronic databases were last searched on 9 July 2012. We also handsearched the
      following conference proceedings: American Academy of Ophthalmology, Association
      for Research in Vision and Ophthalmology, International Council of Opthalmology
      and Societas Ophthalmologica Europaea from 2005 to July 2011. SELECTION CRITERIA:
      We included randomised controlled trials only. DATA COLLECTION AND ANALYSIS: Two
      review authors independently extracted data. Due to the small number of studies
      and the diversity of outcome measures, interventions and participants, we
      presented results narratively. MAIN RESULTS: We found three RCTs with a total of
      58 participants that were eligible for inclusion. There was significant
      variability between the trials in interventions, methodology and outcome measures
      and therefore we did not perform meta-analysis.One study reported on the use of
      2% CsA in maize oil and two on the use of a commercial emulsion of 0.05% CsA. Of
      these three studies, one showed a beneficial effect of topical CsA in controlling
      signs and symptoms of AKC, one in controlling signs of AKC and one did not show
      evidence of an improvement. Only two studies analysed the effect of topical CsA
      in reducing topical steroid use; one showed a significant reduction in topical
      steroid use with CsA, but the other did not show evidence of this improvement. No
      serious adverse events were reported in the trials. AUTHORS' CONCLUSIONS: This
      systematic review highlights the relative scarcity of controlled clinical trials
      assessing the efficacy of topical CsA therapy in AKC and suggests that evidence
      on the efficacy and safety of topical CsA treatment in patients with CsA remains
      limited. However, the data suggest that topical CsA may provide clinical and
      symptomatic relief in AKC and may help to reduce topical steroid use in patients
      with steroid-dependent or steroid-resistant AKC. No serious adverse events were
      reported. Reported adverse events in patients treated with topical CsA include
      intense stinging and eyelid skin maceration. One patient in the placebo group
      developed a severe allergic response to maize antigens. However, the total number
      of patients in the trials was too small to assess the safety of this
      treatment.Additional well-designed and powered RCTs of topical CsA in AKC are
      needed. Ideal study designs should include adequate randomisation and concealment
      of allocation; masking of participants, personnel and outcome assessors; adequate
      follow-up periods and minimisation of attrition bias; and comparison groups with
      similar clinical and epidemiologic characteristics. Samples should be large
      enough to provide sufficient statistical power to assess the safety of CsA and to
      detect clinically relevant treatment effect sizes of the primary outcomes.
      Analyses should be appropriate to the study's design and outcome measures.
      Moreover, standardisation of outcome measures and follow-up periods across
      studies would be beneficial to maximise study comparability.

PMID- 22972133
TI  - Cholinesterase inhibitors for mild cognitive impairment.
AB  - BACKGROUND: Mild cognitive impairment is hypothesised to represent a pre-clinical
      stage of dementia but forms a heterogeneous group with variable prognosis.
      OBJECTIVES: To assess the safety and efficacy of cholinesterase inhibitors in
      people with mild cognitive impairment. SEARCH METHODS: Trials were identified
      from the Cochrane Dementia and Cognitive Improvement Group's Specialised
      Register, which is frequently updated from the major healthcare databases
      (MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs) as well as trial registers and
      grey literature. SELECTION CRITERIA: Double-blind, placebo-controlled randomised
      trials of any cholinesterase inhibitor in people with mild cognitive impairment.
      DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports of
      the included studies, combined by meta-analysis where appropriate, and treatment
      efficacy and risk of adverse events were estimated. MAIN RESULTS: Nine studies
      (from eight published reports) of 5149 individuals with mild cognitive impairment
      (however defined) were included in the review. Limited pooling of results was
      possible owing to different lengths of trials. Meta-analysis of the three studies
      reporting conversion to dementia gives no strong evidence of a beneficial effect
      of cholinesterase inhibitors on the progression to dementia at one, two or three
      years. The risk ratio (RR) for conversion at two years was significantly
      different from unity (0.67; 95% confidence interval (CI) 0.55 to 0.83), but this
      is based on only two studies reported in the same article. There was essentially
      no effect of cholinesterase inhibitors on cognitive test scores.Based on the
      results from 4207 individuals, there were significantly more adverse events in
      the cholinesterase inhibitor groups (RR 1.09; 95% CI 1.02 to 1.16), but no more
      serious adverse events or deaths. Gastrointestinal side effects were much more
      common (diarrhoea: RR 2.10; 95% CI 1.30 to 3.39; nausea: RR 2.97; 95% CI 2.57 to
      3.42; vomiting: RR 4.42; 95% CI 3.23 to 6.05). Cardiac problems were no more
      likely in either group (RR 0.71; 95% CI 0.25 to 2.02). Other side effects
      reported significantly more often in the cholinesterase inhibitor group were
      muscle spasms/leg cramps (RR 7.52; 95% CI 4.34 to 13.02), headache (RR 1.34; 95%
      CI 1.05 to 1.71), syncope or dizziness (RR 1.62; 95% CI 1.36 to 1.93), insomnia
      (RR 1.66; 95% CI 1.36 to 2.02) and abnormal dreams (RR 4.25; 95% CI 2.57 to
      7.04). AUTHORS' CONCLUSIONS: There is very little evidence that cholinesterase
      inhibitors affect progression to dementia or cognitive test scores in mild
      cognitive impairment. This weak evidence is overwhelmed by the increased risk of
      adverse events, particularly gastrointestinal. Cholinesterase inhibitors should
      not be recommended for mild cognitive impairment.

PMID- 22972134
TI  - Tiotropium versus long-acting beta-agonists for stable chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Tiotropium and long-acting beta(2)-agonists (LABAs) are both accepted
      in the routine management for people with stable chronic obstructive pulmonary
      disease (COPD). There are new studies which have compared tiotropium with LABAs,
      including some that have evaluated recently introduced LABAs. OBJECTIVES: To
      compare the relative clinical effects of tiotropium bromide alone versus LABA
      alone, upon measures of quality of life, exacerbations, lung function and serious
      adverse events, in people with stable COPD.To critically appraise and summarise
      current evidence on the costs and cost-effectiveness associated with tiotropium
      compared to LABA in people with COPD. SEARCH METHODS: We identified randomised
      controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of
      trials and economic evaluations from searching NHS EED and HEED (date of last
      search February 2012). We found additional trials from web-based clinical trial
      registers. SELECTION CRITERIA: We included RCTs and full economic evaluations if
      they compared effects of tiotropium alone with LABAs alone in people with COPD.
      We allowed co-administration of standard COPD therapy. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed studies for inclusion, then
      extracted data on study quality and outcomes. We contacted study authors and
      trial sponsors for additional information. We analysed data using the Cochrane
      Review Manager(RevMan 5.1) software. MAIN RESULTS: Seven clinical studies
      totalling 12,223 participants with COPD were included in the review. The studies
      used similar designs and were generally of good methodological quality. Inclusion
      criteria for RCTs were similar across the included studies, although studies
      varied in terms of smoking history and COPD severity of participants. They
      compared tiotropium (which was delivered by HandiHaler in all studies) with
      salmeterol (four studies, 8936 participants), formoterol (one study, 431
      participants) and indacaterol (two studies, 2856 participants). All participants
      were instructed to discontinue anticholinergic or long-acting beta(2)-agonist
      bronchodilators during treatment, but could receive inhaled corticosteroids (ICS)
      at a stable dose. Study duration ranged from 3 to 12 months. We extracted data
      for 11,223 participants. In general, the treatment groups were well matched at
      baseline. Overall, the risk of bias across the included RCTs was low.In the
      analysis of the primary outcomes in this review, a high level of heterogeneity
      amongst studies meant that we did not pool data for St George's Respiratory
      Questionnaire quality of life score. Subgroup analyses based on the type of LABA
      found statistically significant differences among effects on quality of life
      depending on whether tiotropium was compared with salmeterol, formoterol or
      indacaterol. Tiotropium reduced the number of participants experiencing one or
      more exacerbations compared with LABA (odds ratio (OR) 0.86; 95% confidence
      interval (CI) 0.79 to 0.93). For this outcome, there was no difference seen among
      the different types of LABA. There was no statistical difference in mortality
      observed between the treatment groups.For secondary outcomes, tiotropium was
      associated with a reduction in the number of COPD exacerbations leading to
      hospitalisation compared with LABA treatment (OR 0.87; 95% 0.77 to 0.99), but not
      in the overall rate of all-cause hospitalisations. There was no statistically
      significant difference in forced expiratory volume in one second (FEV(1)) or
      symptom score between tiotropium and LABA-treated participants. There was a lower
      rate of non-fatal serious adverse events recorded with tiotropium compared with
      LABA (OR 0.88; 95% CI 0.78 to 0.99). The tiotropium group was also associated
      with a lower rate of study withdrawals (OR 0.89; 95% CI 0.81 to 0.99).We
      identified six full economic evaluations assessing the cost and cost
      effectiveness of tiotropium and salmeterol. The studies were based on an economic
      model or empirical analysis of clinical data from RCTs. They all looked at
      maintenance costs and the costs for COPD exacerbations, including respiratory
      medications and hospitalisations. The setting for the evaluations was primary and
      secondary care in the UK, Greece, Netherlands, Spain and USA. All the studies
      estimated tiotropium to be superior to salmeterol based on better clinical
      outcomes (exacerbations or quality of life) and/or lower total costs. However,
      the authors of all evaluations reported there was substantial uncertainty around
      the results. AUTHORS' CONCLUSIONS: In people with COPD, the evidence is equivocal
      as to whether or not tiotropium offers greater benefit than LABAs in improving
      quality of life; however, this is complicated by differences in effect among the
      LABA types. Tiotropium was more effective than LABAs as a group in preventing
      COPD exacerbations and disease-related hospitalisations, although there were no
      statistical differences between groups in overall hospitalisation rates or
      mortality during the study periods. There were fewer serious adverse events and
      study withdrawals recorded with tiotropium compared with LABAs. Symptom
      improvement and changes in lung function were similar between the treatment
      groups. Given the small number of studies to date, with high levels of
      heterogeneity among them, one approach may be to give a COPD patient a
      substantial trial of tiotropium, followed by a LABA (or vice versa), then to
      continue prescribing the long-acting bronchodilator that the patient prefers.
      Further studies are needed to compare tiotropium with different LABAs, which are
      currently ongoing. The available economic evidence indicates that tiotropium may
      be cost-effective compared with salmeterol in several specific settings, but
      there is considerable uncertainty around this finding.

PMID- 22972135
TI  - Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host
      disease after allogeneic stem cell or bone marrow transplantation in adults.
AB  - BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is an
      established treatment for many malignant and non-malignant haematological
      disorders. Graft-versus-host disease (GVHD), a condition frequently occurring
      after HSCT, is the result of host tissues being attacked by donor immune cells.
      One strategy for the prevention of GVHD is the administration of anti-thymocyte
      globulins (ATG), a set of polyclonal antibodies directed against a variety of
      immune cell epitopes, leading to immunosuppression and immunomodulation.
      OBJECTIVES: To assess the effect of ATG used for the prevention of graft-versus
      host disease (GVHD) in patients undergoing allogeneic HSCT with regard to overall
      survival, incidence and severity of acute and chronic GVHD, incidence of relapse,
      incidence of infectious complications, non-relapse mortality, early mortality
      within 100 days of transplantation, progression-free survival, quality of life
      and adverse events. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE
      (January 1950 to February 2012), trials registries and conference proceedings.
      The search was conducted in October 2010 and was updated in July 2011 and
      February 2012. We did not apply any language restrictions. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) investigating the impact of ATG on
      GVHD prophylaxis in adults suffering from haematological diseases and undergoing
      allogeneic HSCT. Treatment arms had to differ only in the addition of ATG to the
      standard GVHD prophylaxis regimen. DATA COLLECTION AND ANALYSIS: Two review
      authors screened abstracts, extracted data and analysed the data independently.
      We contacted study authors for additional information. MAIN RESULTS: We included
      in the meta-analysis six RCTs which met the pre-defined selection criteria,
      involving a total of 568 participants. Quality of data reporting was
      heterogeneous among these studies with a lack of detailed information in the
      early studies.The primary outcome of overall survival was not significantly
      changed by the addition of ATG for the prophylaxis of GVHD (harms ratio (HR)
      0.88; 95% CI 0.67 to 1.15, P = 0.33).The incidence of treatment-requiring or
      severe acute GVHD (grade II to IV) was significantly lower in patients who
      received ATG (risk ratio (RR) 0.68; 95% CI 0.55 to 0.85, P = 0.009; number needed
      to treat (NNT) 8). Also, the incidence of severe acute GVHD (grade III to IV) was
      significantly reduced (HR 0.53; 95% CI 0.33 to 0.85, P = 0.0005; NNT 7) but
      comparable data were available for rabbit ATG only. However, pooled study results
      regarding the incidence of acute GVHD of all grades (I to IV) showed no
      significant benefit of ATG treatment (RR 0.89; 95% CI 0.74 to 1.06, P =
      0.20).Meta-analysis of data regarding the incidence of overall chronic GVHD
      (both, limited and extensive) was not possible. Nevertheless, studies reporting
      on extensive chronic GVHD (only studies evaluating rabbit ATG) suggested a lower
      incidence of extensive chronic GVHD whereas others that only reported on overall
      chronic GVHD did not show an advantage for ATG.Pooled results regarding the
      incidence of relapse were not significantly different (RR 1.13; 95% CI 0.75 to
      1.68, P = 0.56), as well as pooled results regarding non-relapse mortality (HR
      0.82; 95% CI 0.55 to 1.24, P = 0.35).Due to the lack of comparable data, we could
      not perform meta-analysis of data regarding the incidence of chronic GVHD,
      relapse-related mortality, progression-free survival, quality of life, adverse
      events and engraftment. AUTHORS' CONCLUSIONS: Our systematic review suggests that
      the addition of ATG during allogeneic HSCT significantly reduces the incidence of
      severe grades (II to IV) of acute GvHD, whereas the incidence of overall acute
      GVHD (grades I to IV) was not significantly lowered. This indicates a reduction
      of the severity but not the incidence of acute GVHD. However, this effect did not
      lead to a significant improvement of overall survival, which may be due to the
      severe potential side effects of the consecutively increased
      immunosuppression.Furthermore, future research is needed to clarify the effect of
      ATG on the incidence and severity of chronic GVHD and consequently on all aspects
      of quality of life.From the currently available data, no recommendation on the
      general use of ATG in allogeneic HSCT can be supported. Therefore, a careful
      consideration of the use of ATG based on the patient's condition and the risk
      factors of the transplantation setting should be made.

PMID- 22972136
TI  - Antibiotics for otitis media with effusion in children.
AB  - BACKGROUND: Otitis media with effusion (OME) is characterised by an accumulation
      of fluid in the middle ear behind an intact tympanic membrane, without the
      symptoms or signs of acute infection. In approximately one in three children with
      OME, however, a bacterial pathogen is identified in the middle ear fluid. In most
      cases, OME causes mild hearing impairment of short duration. When experienced in
      early life and when episodes of (bilateral) OME persist or recur, the associated
      hearing loss may be significant and have a negative impact on speech development
      and behaviour. Since most cases of OME will resolve spontaneously, only children
      with persistent middle ear effusion and associated hearing loss potentially
      require treatment. Previous Cochrane reviews have focused on the effectiveness of
      ventilation tube insertion, adenoidectomy, autoinflation, antihistamines,
      decongestants, and oral and topical intranasal steroids in OME. This review
      focuses on the effectiveness of antibiotics in children with OME. OBJECTIVES: To
      assess the effects of antibiotics in children up to 18 years with OME. SEARCH
      METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials
      Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed;
      EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts;
      ICTRP and additional sources for published and unpublished trials. The date of
      the search was 22 February 2012. SELECTION CRITERIA: Randomised controlled trials
      comparing oral antibiotics with placebo, no treatment or therapy of unproven
      effectiveness. Our primary outcome was complete resolution of OME at two to three
      months. Secondary outcomes included resolution of OME at other time points,
      hearing, language and speech, ventilation tube insertion and adverse effects.
      DATA COLLECTION AND ANALYSIS: Two authors independently extracted data using
      standardised data extraction forms and assessed the quality of the included
      studies using the Cochrane 'Risk of bias' tool. We presented dichotomous results
      as risk differences as well as risk ratios, with their 95% confidence intervals.
      If heterogeneity was greater than 75% we did not pool data. MAIN RESULTS: We
      included 23 studies (3027 children) covering a range of antibiotics,
      participants, outcome measures and time points of evaluation. Overall, we
      assessed the studies as generally being at low risk of bias.Our primary outcome
      was complete resolution of OME at two to three months. The differences
      (improvement) in the proportion of children having such resolution (risk
      difference (RD)) in the five individual included studies ranged from 1% (RD 0.01,
      95% CI -0.11 to 0.12; not significant) to 45% (RD 0.45, 95% CI 0.25 to 0.65).
      Results from these studies could not be pooled due to clinical and statistical
      heterogeneity.Pooled analysis of data for complete resolution at more than six
      months was possible, with an increase in resolution of 13% (RD 0.13, 95% CI 0.06
      to 0.19).Pooled analysis was also possible for complete resolution at the end of
      treatment, with the following increases in resolution rates: 17% (RD 0.17, 95% CI
      0.09 to 0.24) for treatment for 10 days to two weeks, 34% (RD 0.34, 95% CI 0.19
      to 0.50) for treatment for four weeks, 32% (RD 0.32, 95% CI 0.17 to 0.47) for
      treatment for three months, and 14% (RD 0.14, 95% CI 0.03 to 0.24) for treatment
      continuously for at least six months.We were unable to find evidence of a
      substantial improvement in hearing as a result of the use of antibiotics for
      otitis media with effusion; nor did we find an effect on the rate of ventilation
      tube insertion. We did not identify any trials that looked at speech, language
      and cognitive development or quality of life. Data on the adverse effects of
      antibiotic treatment reported in six studies could not be pooled due to high
      heterogeneity. Increases in the occurrence of adverse events varied from 3% (RD
      0.03, 95% CI -0.01 to 0.07; not significant) to 33% (RD 0.33, 95% CI 0.22 to
      0.44) in the individual studies. AUTHORS' CONCLUSIONS: The results of our review
      do not support the routine use of antibiotics for children up to 18 years with
      otitis media with effusion. The largest effects of antibiotics were seen in
      children treated continuously for four weeks and three months. Even when clear
      and relevant benefits of antibiotics have been demonstrated, these must be
      balanced against the potential adverse effects when making treatment decisions.
      Immediate adverse effects of antibiotics are common and the emergence of
      bacterial resistance has been causally linked to the widespread use of
      antibiotics for common conditions such as otitis media.

PMID- 22972137
TI  - Arthroplasty versus fusion in single-level cervical degenerative disc disease.
AB  - BACKGROUND: There is ongoing debate about whether fusion or arthroplasty is
      superior in the treatment of single level cervical degenerative disc disease.
      Mainly because the intended advantage of arthroplasty over fusion, that is, the
      prevention of symptoms due to adjacent segment degeneration in the long term, is
      not confirmed yet. Until sufficient long-term results become available, it is
      important to know whether results of one of the two treatments are superior to
      the other in the first one to two years. OBJECTIVES: To assess the effects of
      arthroplasty versus fusion for radiculopathy or myelopathy, or both due to single
      level cervical degenerative disc disease. SEARCH METHODS: We searched the
      following databases for randomised controlled trials (RCTs): CENTRAL (The
      Cochrane Library 2011, Issue 2), MEDLINE, EMBASE, and EBMR. Additionally, we
      searched the System for Information on Grey Literature (SIGLE), subheading
      Biological and Medical Sciences, the US Food and Drug Administration (FDA)
      database on medical devices, and Clinicaltrials.gov to identify trials in
      progress. We also screened the reference list of all selected papers. Date of
      search: 25 May 2011. SELECTION CRITERIA: We included RCTs that directly compared
      any type of cervical fusion with any type of arthroplasty, with at least one year
      of follow-up. Primary outcomes were arm pain, neck pain, neck-related functional
      status, patient satisfaction, neurological outcome, and global health status.
      Secondary outcomes were the presence of (radiological) fusion, revision surgery
      at the treated level, secondary surgery on adjacent levels, segmental mobility of
      treated and adjacent levels, and work status. DATA COLLECTION AND ANALYSIS: Study
      selection was performed independently by three review authors, and 'Risk of bias'
      assessment and data extraction were performed by two review authors. In case of
      missing data or insufficient information for a judgement about risk of bias, we
      tried to contact the study authors or the study sponsor. The data were entered
      into RevMan by one review author and subsequently checked by a second review
      author. We assessed the quality of evidence using GRADE. We analysed
      heterogeneity and performed sensitivity analyses for the pooled analyses. MAIN
      RESULTS: We included nine studies (2400 participants), five of which had a low
      risk of bias. Eight of these studies were industry sponsored. The most important
      results showed low-quality evidence for a small but significant difference in
      alleviation of arm pain at one to two years in favour of arthroplasty (mean
      difference (MD) -1.54; 95% confidence interval (CI) -2.86 to -0.22; 100-point
      scale). A small study effect could not be ruled out for this outcome in the
      sensitivity analyses. This means that smaller studies (or small published subsets
      of larger studies) showed larger differences for this outcome, which may indicate
      publication bias. Also, moderate-quality evidence showed a small difference in
      neck-related functional status at one to two years in favour of arthroplasty (MD 
      2.79; 95% CI -4.73 to -0.85; 100-point scale) and a small difference in
      neurological outcome in favour of arthroplasty (risk ratio (RR) 1.05; 95% CI 1.01
      to 1.09). These two outcomes were robust to sensitivity analyses. For none of the
      primary outcomes, was a clinically relevant difference shown. Additionally, there
      was high-quality evidence for a large, statistically significant difference in
      segmental mobility at one to two years (measured as degrees segmental range of
      motion) at the treated level (MD 6.90; 95% CI 5.45 to 8.35). There was low
      quality evidence that there was no statistically significant difference in
      secondary surgery at the adjacent levels at one to two years (RR 0.60; 95% CI
      0.35 to 1.02). The latter was not robust to sensitivity analyses. AUTHORS'
      CONCLUSIONS: There was a tendency for clinical results to be in favour of
      arthroplasty; often these were statistically significant. However, differences in
      effect size were invariably small and not clinically relevant for all primary
      outcomes. Significance was often gained or lost in the varying sensitivity
      analyses, probably owing to the relatively small number of studies, in
      combination with the small differences that were found. Given the fact that all
      of the included studies were not blinded, this could be due to patient or carer
      expectations. However, at this time both treatments can be seen as valid options
      with respect to results at a maximum of one to two years. Given the current
      absence of truly long-term results, use of these mobile disc prostheses should
      still be limited to clinical trials. There was high-quality evidence that the
      goal of preservation of segmental mobility in arthroplasty was met. A
      statistically significant effect on the incidence of secondary symptoms at
      adjacent levels, the primary goal of arthroplasty over fusion, was not found at
      one to two years. If there was a protective effect, this should become clearer
      over time. A future update, when studies with 'truly long-term' results (five
      years or more) become available, should focus on this issue.

PMID- 22972138
TI  - Surfactant therapy for bronchiolitis in critically ill infants.
AB  - BACKGROUND: Bronchiolitis is one of the most frequent causes of respiratory
      failure in infants; some infants will require intensive care and mechanical
      ventilation. There is lack of evidence regarding effective treatment for
      bronchiolitis other than supportive care. Abnormalities of surfactant quantity or
      quality (or both) have been observed in severe cases of bronchiolitis. Exogenous
      surfactant administration appears to favourably change the haemodynamics of the
      lungs and may be a potentially promising therapy for severe bronchiolitis. 
      OBJECTIVES: To evaluate the efficacy of exogenous surfactant administration (i.e.
      intratracheal administration of surfactant of any type (whether animal-derived or
      synthetic), at any dose and at any time after start of ventilation) compared to
      placebo, no intervention or standard care in reducing mortality and the duration
      of ventilation in infants and children with bronchiolitis requiring mechanical
      ventilation. SEARCH METHODS: We searched CENTRAL 2012, Issue 4 which contains the
      Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1948
      to May week 1, 2012), EMBASE (1974 to May 2012), CINAHL (1982 to May 2012),
      LILACS (1985 to May 2012) and Web of Science (1985 to May 2012). SELECTION
      CRITERIA: We considered prospective, randomised controlled trials (RCTs) and
      quasi-RCTs evaluating the effect of exogenous surfactant in infants and children
      with bronchiolitis requiring mechanical ventilation. DATA COLLECTION AND
      ANALYSIS: Two review authors selected studies independently. We extracted the
      data using a predefined proforma, independently analysed the data and performed
      meta-analyses. MAIN RESULTS: We included three small RCTs enrolling 79
      participants. Two trials did not use a placebo in the control arms and the third
      trial used air placebo. Two included studies did not describe mortality. We
      judged some of the included studies to have an unclear risk of bias but none of
      the included studies had a high risk of bias. Our pooled analysis of the three
      trials revealed that duration of mechanical ventilation was not different between
      the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to
      4.35 hours) but duration of intensive care unit (ICU) stay was less in the
      surfactant group compared to the control group: MD -3.31 (95% CI -6.38 to -0.25
      days). After excluding one trial which produced significant heterogeneity, the
      duration of mechanical ventilation and duration of ICU stay were significantly
      lower in the surfactant group compared to the control group: MD -28.99 (95% CI 
      40.10 to -17.87 hours) and MD -1.81 (95% CI -2.42 to -1.19 days), respectively.
      Use of surfactant had favourable effects on oxygenation and CO(2) elimination. No
      adverse effects and no complications were observed in any of the three included
      studies. AUTHORS' CONCLUSIONS: The available evidence is insufficient to
      establish the effectiveness of surfactant therapy for bronchiolitis in critically
      ill infants who require mechanical ventilation. There is a need for larger trials
      with adequate power and a cost-effectiveness analysis to evaluate the
      effectiveness of exogenous surfactant therapy for infants with bronchiolitis who
      require intensive care management.

PMID- 22972139
TI  - Iron chelators for acute stroke.
AB  - BACKGROUND: Stroke is a serious public health problem that causes morbidity and
      mortality throughout the world. Iron chelators are potential neuroprotective
      drugs to treat patients with both hemorrhagic and ischemic stroke. OBJECTIVES: To
      evaluate the effectiveness and safety of the administration of iron chelators in
      patients with acute stroke. SEARCH METHODS: We searched the Cochrane Stroke Group
      Trials Register (May 2012), the Chinese Stroke Trials Register (May 2012), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2012, Issue 1), MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), Science
      Citation Index (1980 to May 2012) and three Chinese databases. In an effort to
      identify further published, unpublished and ongoing trials we searched ongoing
      trials registers, checked reference lists, and contacted authors and
      pharmaceutical companies. SELECTION CRITERIA: We included published and
      unpublished randomized controlled trials (RCTs) of iron chelator versus no iron
      chelator or placebo for the treatment of acute stroke. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened search results to identify
      the full texts of potentially relevant studies for inclusion. From the results of
      the screened searches two review authors independently selected trials meeting
      the inclusion criteria, with no disagreement. MAIN RESULTS: We found no completed
      RCTs eligible for inclusion in the review. We identified one ongoing RCT but no
      data were available. AUTHORS' CONCLUSIONS: There is insufficient evidence to
      support or refute the use of iron chelators for the treatment of acute stroke.
      Further RCTs are required to assess the effect of iron chelators in people with
      acute stroke.

PMID- 22972140
TI  - Inhaled analgesia for pain management in labour.
AB  - BACKGROUND: Many women would like to have a choice in pain relief during labour
      and also would like to avoid invasive methods of pain management in labour.
      Inhaled analgesia during labour involves the self-administered inhalation of sub
      anaesthetic concentrations of agents while the mother remains awake and her
      protective laryngeal reflexes remain intact. Most of the agents are easy to
      administer, can be started in less than a minute and become effective within a
      minute. OBJECTIVES: To examine the effects of all modalities of inhaled analgesia
      on the mother and the newborn for mothers who planned to have a vaginal delivery.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 January 2012), ClinicalTrials.gov, and Current Controlled Trials (2
      June 2012), handsearched conference proceedings from the American Society of
      Clinical Anesthesia (from 1990 to 2011), contacted content experts and trialists
      and searched reference lists of retrieved studies. SELECTION CRITERIA: Randomised
      controlled trials comparing inhaled analgesia with other inhaled analgesia or
      placebo or no treatment or other methods of non-pharmacological pain management
      in labour. DATA COLLECTION AND ANALYSIS: Review authors independently assessed
      trials for eligibility, methodological quality and extracted all data. Data were
      double checked for accuracy. MAIN RESULTS: Twenty-six studies, randomising 2959
      women, were included in this review.Inhaled analgesia versus a different type of
      inhaled analgesia Pain relief was measured using a Visual Analogue Scale (VAS)
      from 0 to 100 mm where 100 corresponds to the most relief. Pain intensity was
      measured using a VAS from 0 to 100 mm, where 0 corresponds to no pain at all and
      100 corresponds to the worst pain. The highest score for pain relief is the most
      positive in contrast to 'pain intensity' in which the higher score is more
      negative. Flurane derivatives were found to offer better pain relief than nitrous
      oxide in first stage of labour as measured by a lower pain intensity score
      (average mean difference (MD) 14.39, 95% confidence interval (CI) 4.41 to 24.37,
      three studies, 70 women), also a higher pain relief score for flurane derivatives
      compared with nitrous oxide (average MD -16.32, 95% CI -26.85 to -5.79, two
      studies, 70 women). Substantial heterogeneity was found in the analyses of pain
      intensity (P = 0.003) and in the analysis of pain relief (P = 0.002).These
      findings should be considered with caution because of the questionable design of
      the included cross-over trials. More nausea was found in the nitrous oxide group
      compared with the flurane derivatives group (risk ratio (RR) 6.60 95% CI 1.85 to
      23.52, two studies, 98 women).Inhaled analgesia versus placebo or no treatment
      Placebo or no treatment was found to offer less pain relief compared to nitrous
      oxide (average RR 0.06, 95% CI 0.01 to 0.34, two studies, 310 women; MD -3.50,
      95% CI -3.75 to -3.25, one study, 509 women). However, nitrous oxide resulted in
      more side effects for women such as nausea (RR 43.10, 95% CI 2.63 to 706.74, one
      study, 509 women), vomiting (RR 9.05, 95% CI 1.18 to 69.32, two studies, 619
      women), dizziness (RR 113.98, 95% CI 7.09 to 1833.69, one study, 509 women) and
      drowsiness (RR 77.59, 95% CI 4.80 to 1254.96, one study, 509 women) when compared
      with placebo or no treatment.There were no significant differences found for any
      of the outcomes in the studies comparing one strength versus a different strength
      of inhaled analgesia, in studies comparing different delivery systems or in the
      study comparing inhaled analgesia with TENS.Due to lack of data, the following
      outcomes were not analysed within the review: sense of control; satisfaction with
      childbirth experience; effect on mother/baby interaction; breastfeeding;
      admission to special care baby unit; poor infant outcomes at long-term follow-up;
      or costs. AUTHORS' CONCLUSIONS: Inhaled analgesia appears to be effective in
      reducing pain intensity and in giving pain relief in labour. However, substantial
      heterogeneity was detected for pain intensity. Furthermore, nitrous oxide appears
      to result in more side effects compared with flurane derivatives. Flurane
      derivatives result in more drowsiness when compared with nitrous oxide. When
      inhaled analgesia is compared with no treatment or placebo, nitrous oxide appears
      to result in even more side effects such as nausea, vomiting, dizziness and
      drowsiness. There is no evidence for differences for any of the outcomes
      comparing one strength verus a different strength of inhaled analgesia, comparing
      different delivery systems or comparing inhaled analgesia with TENS.

PMID- 22972141
TI  - Amniotic membrane transplantation for acute ocular burns.
AB  - BACKGROUND: Ocular surface burns can be caused by chemicals (alkalis and acids)
      or by direct heat. Amniotic membrane transplantation (AMT) performed in the acute
      phase (day 0 to day 7) of an ocular surface burn is reported to relieve pain,
      accelerate healing and reduce scarring and blood vessel formation. The surgery
      involves applying a patch of amniotic membrane (AM) over the entire ocular
      surface up to the eyelid margins. OBJECTIVES: To assess the effects of AMT on the
      eyes of people having suffered acute ocular surface burns. SEARCH METHODS: We
      searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June
      2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean
      Literature on Health Sciences (LILACS) (January 1982 to June 2012), the
      metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use
      any date or language restrictions in the electronic searches for trials. We last
      searched the electronic databases on 11 June 2012. SELECTION CRITERIA: We
      included randomised trials of medical therapy and AMT applied in the first seven
      days after an ocular surface burn compared to medical therapy alone. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias of
      included studies and extracted relevant data. We contacted trial investigators
      for missing information. We summarised data using risk ratios (RRs) and mean
      differences (MDs) as appropriate. MAIN RESULTS: We included one RCT of 100
      participants with ocular burns that were randomised to treatment with AMT and
      medical therapy or medical therapy alone. A subset of patients (n = 68) who were
      treated within the first seven days of the injury met the inclusion criteria and
      were included in the analysis. The remaining 32 eyes were excluded. The included
      subset consisted of 36 moderate (Dua classification II-III) and 32 severe (Dua
      classification IV-VI) ocular burns from alkali, acid and thermal injuries. In the
      moderate category, 13/20 control eyes and 14/16 treatment eyes had complete
      epithelialisation by 21 days. The RR of failure of epithelialisation by day 21
      was 0.18 in the treatment group (95% confidence interval (CI) 0.02 to 1.31; P =
      0.09). Mean LogMAR final visual acuities were 0.06 (standard deviation (SD) 0.10)
      in the treatment group and 0.38 (SD 0.52) in the control group, representing a MD
      of -0.32 (95% CI -0.05 to -0.59). In the severe category, 1/17 treatment and 1/15
      control eyes were epithelialised by day 21. The RR of failure of
      epithelialisation in the treatment group was 1.01 (95% CI 0.84 to 1.21; P =
      0.93). Final visual acuity was 1.77 (SD 1.31) in the treated eyes and 1.64 (SD
      1.48) in the control group (MD 0.13; 95% CI -0.88 to 1.14). The risks of
      performance and detection biases were high, because treating personnel and
      outcome assessors could not be masked to treatment. There was also a high risk of
      bias in the visual outcomes of the moderate category, since mean visual acuity
      was significantly worse at presentation in the control eyes. This reduced
      confidence in the study findings. AUTHORS' CONCLUSIONS: Conclusive evidence
      supporting the treatment of acute ocular surface burns with AMT is lacking.
      Heterogeneity of disease presentation, variations in treatment, undefined
      criteria for treatment success and failure, and non-uniform outcome measures are
      some of the factors complicating the search for clear evidence regarding this
      treatment.

PMID- 22972142
TI  - Interventions to improve the use of systematic reviews in decision-making by
      health system managers, policy makers and clinicians.
AB  - BACKGROUND: Systematic reviews provide a transparent and robust summary of
      existing research. However, health system managers, national and local policy
      makers and healthcare professionals can face several obstacles when attempting to
      utilise this evidence. These include constraints operating within the health
      system, dealing with a large volume of research evidence and difficulties in
      adapting evidence from systematic reviews so that it is locally relevant. In an
      attempt to increase the use of systematic review evidence in decision-making a
      number of interventions have been developed. These include summaries of
      systematic review evidence that are designed to improve the accessibility of the
      findings of systematic reviews (often referred to as information products) and
      changes to organisational structures, such as employing specialist groups to
      synthesise the evidence to inform local decision-making. OBJECTIVES: To identify
      and assess the effects of information products based on the findings of
      systematic review evidence and organisational supports and processes designed to
      support the uptake of systematic review evidence by health system managers,
      policy makers and healthcare professionals. SEARCH METHODS: We searched The
      Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, and Health Economic
      Evaluations Database. We also handsearched two journals (Implementation Science
      and Evidence and Policy), Cochrane Colloquium abstracts, websites of key
      organisations and reference lists of studies considered for inclusion. Searches
      were run from 1992 to March 2011 on all databases, an update search to March 2012
      was run on MEDLINE only. SELECTION CRITERIA: Randomised controlled trials (RCTs),
      interrupted time-series (ITS) and controlled before-after studies (CBA) of
      interventions designed to aid the use of systematic reviews in healthcare
      decision-making were considered. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted the data and assessed the study quality. We extracted the
      median value across similar outcomes for each study and reported the range of
      values for each median value. We calculated the median of the two middlemost
      values if an even number of outcomes were reported. MAIN RESULTS: We included
      eight studies evaluating the effectiveness of different interventions designed to
      support the uptake of systematic review evidence. The overall quality of the
      evidence was very low to moderate.Two cluster RCTs evaluated the effectiveness of
      multifaceted interventions, which contained access to systematic reviews relevant
      to reproductive health, to change obstetric care; the high baseline performance
      in some of the key clinical indicators limited the findings of these studies.
      There were no statistically significant effects on clinical practice for all but
      one of the clinical indicators in selected obstetric units in Thailand (median
      effect size 4.2%, range -11.2% to 18.2%) and none in Mexico (median effect size
      3.5%, range 0.1% to 19.0%). In the second cluster RCT there were no statistically
      significant differences in selected obstetric units in the UK (median effect RR
      0.92; range RR 0.57 to RR 1.10). One RCT evaluated the perceived understanding
      and ease of use of summary of findings tables in Cochrane Reviews. The median
      effect of the differences in responses for the acceptability of including summary
      of findings tables in Cochrane Reviews versus not including them was 16%, range
      1% to 28%. One RCT evaluated the effect of an analgesic league table, derived
      from systematic review evidence, and there was no statistically significant
      effect on self-reported pain. Only one RCT evaluated an organisational
      intervention (which included a knowledge broker, access to a repository of
      systematic reviews and provision of tailored messages), and reported no
      statistically significant difference in evidence informed programme
      planning.Three interrupted time series studies evaluated the dissemination of
      printed bulletins based on evidence from systematic reviews. A statistically
      significant reduction in the rates of surgery for glue ear in children under 10
      years (mean annual decline of -10.1%; 95% CI -7.9 to -12.3) and in children under
      15 years (quarterly reduction -0.044; 95% CI -0.080 to -0.011) was reported. The
      distribution to general practitioners of a bulletin on the treatment of
      depression was associated with a statistically significant lower prescribing rate
      each quarter than that predicted by the rates of prescribing observed before the
      distribution of the bulletin (8.2%; P = 0.005). AUTHORS' CONCLUSIONS: Mass
      mailing a printed bulletin which summarises systematic review evidence may
      improve evidence-based practice when there is a single clear message, if the
      change is relatively simple to accomplish, and there is a growing awareness by
      users of the evidence that a change in practice is required. If the intention is
      to develop awareness and knowledge of systematic review evidence, and the skills
      for implementing this evidence, a multifaceted intervention that addresses each
      of these aims may be required, though there is insufficient evidence to support
      this approach.

PMID- 22972143
TI  - Magnesium for skeletal muscle cramps.
AB  - BACKGROUND: Skeletal muscle cramps are common and often presented to physicians
      in association with pregnancy, advanced age, exercise or disorders of the motor
      neuron (such as amyotrophic lateral sclerosis). Magnesium supplements are
      marketed for the prophylaxis of cramps but the efficacy of magnesium for this
      indication has never been evaluated by systematic review. OBJECTIVES: To assess
      the effects of magnesium supplementation compared to no treatment, placebo
      control or other cramp therapies in people with skeletal muscle cramps.   SEARCH
      METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized
      Register (11 October 2011), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (2011, Issue 3), MEDLINE (January 1966 to September 2011), EMBASE
      (January 1980 to September 2011), LILACS (January 1982 to September 2011), CINAHL
      Plus (January 1937 to September 2011), AMED (January 1985 to October 2011) and
      SPORTDiscus (January 1975 to September 2011). SELECTION CRITERIA: Randomized
      controlled trials (RCTs) of magnesium supplementation (in any form) to prevent
      skeletal muscle cramps in any patient group (i.e. all clinical presentations of
      cramp). We considered comparisons of magnesium with no treatment, placebo
      control, or other therapy. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected trials for inclusion and extracted data. Two authors
      assessed risk of bias. We attempted to contact all study authors and obtained
      patient level data for three of the included trials, one of which was
      unpublished. All data on adverse effects were collected from the included RCTs.
      MAIN RESULTS: We identified seven trials (five parallel, two cross-over)
      enrolling a total of 406 individuals amongst whom 118 cross-over participants
      additionally served as their own controls. Three trials enrolled women with
      pregnancy-associated leg cramps (N = 202) and four trials enrolled idiopathic
      cramp sufferers (N = 322 including cross-over controls). Magnesium was compared
      to placebo in six trials and to no treatment in one trial.For idiopathic cramps
      (largely older adults presumed to have nocturnal leg cramps), differences in
      measures of cramp frequency, magnesium versus placebo, were small, not
      statistically significant, and without heterogeneity (I(2) = 0%). This includes
      the primary endpoint, percentage change from baseline in the number of cramps per
      week at four weeks (-3.93%, 95% confidence interval (CI) -21.12% to 13.26%,
      moderate quality evidence) and the difference in the number of cramps per week at
      four weeks (0.01 cramps/week, 95% CI -0.52 to 0.55, moderate quality evidence).
      The percentage of individuals experiencing a 25% or better reduction in cramp
      rate from baseline was also no different, being 8% lower in the magnesium group
      (95% CI -28% to 12%, moderate quality evidence). Similarly, no statistically
      significant difference was found at four weeks in measures of cramp intensity
      (moderate quality evidence) or cramp duration (low quality evidence).Meta
      analysis was not possible for trials of pregnancy-associated leg cramps. The
      single study comparing magnesium to no treatment failed to find statistically
      significant benefit on a three-point ordinal scale of overall treatment efficacy.
      The two trials comparing magnesium to placebo differed in that one trial found no
      benefit on frequency or intensity measures while the other found benefit for
      both.Withdrawals due to adverse events were not significantly different than
      placebo. While we could not determine the number of subjects with minor adverse
      events, studies of oral magnesium generally described potential side effects as
      similar in frequency to placebo. AUTHORS' CONCLUSIONS: It is unlikely that
      magnesium supplementation provides clinically meaningful cramp prophylaxis to
      older adults experiencing skeletal muscle cramps. In contrast, for those
      experiencing pregnancy-associated rest cramps the literature is conflicting and
      further research in this patient population is needed. We found no randomized
      controlled trials evaluating magnesium for exercise-associated muscle cramps or
      disease state-associated muscle cramps (for example amyotrophic lateral
      sclerosis/motor neuron disease).

PMID- 22972144
TI  - Interventions for reducing wrong-site surgery and invasive procedures.
AB  - BACKGROUND: Specific clinical interventions are needed to reduce wrong-site
      surgery, which is a rare but potentially disastrous clinical error. Risk factors
      contributing to wrong-site surgery are variable and complex. The introduction of
      organisational and professional clinical strategies may have a role in minimising
      wrong-site surgery. OBJECTIVES: To evaluate the effectiveness of organisational
      and professional interventions for reducing wrong-site surgery (including wrong
      site, wrong-side, wrong-procedure and wrong-patient surgery), including non
      surgical invasive procedures such as regional blocks, dermatological, obstetric
      and dental procedures and emergency surgical procedures not undertaken within the
      operating theatre. SEARCH METHODS: We searched the following electronic
      databases: the Cochrane Effective Practice and Organisation of Care (EPOC) Group
      Specialised Register (June 2011), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library 2011, Issue 6), MEDLINE (1948-June 2011), EMBASE
      (1947-June 2011), CINAHL (1980-June 2011), Dissertations and Theses (1861-June
      2011), African Index Medicus, Latin American and Caribbean Health Sciences
      database, Virtual Health Library, Pan American Health Organization Database and
      the World Health Organization Library Information System. A grey literature
      search was conducted. Database searches were conducted June 2011. SELECTION
      CRITERIA: We included randomised controlled trials (RCTs), non-randomised
      controlled trials, controlled before-after studies (CBAs) with at least two
      intervention and control sites, and interrupted-time-series (ITS) studies where
      the intervention time was clearly defined and there were at least three data
      points before and three after the intervention. Studies evaluated the
      effectiveness of organisational and professional interventions for reducing wrong
      site surgery, including wrong site, wrong side and wrong procedure. Participants
      included all healthcare professionals providing care to surgical patients;
      studies where patients were involved to avoid the incorrect procedures or studies
      with interventions addressed to healthcare managers, administrators, stakeholders
      or health insurers. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the quality and abstracted data of all eligible studies
      using a standardised data extraction form, modified from the Cochrane EPOC
      checklists. We contacted study authors for additional information. MAIN RESULTS:
      We included one study in this review. One ITS study evaluated a targeted
      educational intervention aiming at reducing the incidence of wrong-site tooth
      extractions. The intervention included examination of previous cases of wrong
      site tooth extractions, educational intervention including a presentation of
      cases of erroneous extractions, explanation of relevant clinical guidelines and
      feedback by an instructor. Data was re-analysed using the Prais-Winsten time
      series and the change in level for annual number of mishaps was statistically
      significant at -4.52 (95% confidence interval (CI) -6.83 to -2.217) (standard
      error (SE) 0.5380). The change in slope was statistically significant at -1.16
      (95% CI -2.22 to -0.10) (SE 0.2472; P < 0.05). AUTHORS' CONCLUSIONS: The findings
      of this review identified one ITS study for a non-medical procedure conducted in
      a dental outpatient setting. The study suggested that the use of a specific
      educational intervention, in the above-mentioned context, which targets junior
      dental staff using a training session that included cases of wrong-site surgery,
      presentation of clinical guidelines and feedback by the instructor, was
      associated with a reduction in the incidence of wrong-site tooth extractions.
      Given the nature of the intervention in a very specific population, application
      of these results to a broader population undergoing other forms of surgery or
      invasive procedures should be undertaken cautiously.

PMID- 22972145
TI  - Transarterial (chemo)embolisation versus no intervention or placebo intervention
      for liver metastases.
AB  - BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma
      are the two most common malignant tumours to affect the liver. The liver is
      second only to the lymph nodes as the most common site for metastatic disease.
      More than half of the patients with metastatic liver disease will die from
      metastatic complications. Chemoembolisation is based on the concept that the
      blood supply to hepatic tumours originates predominantly from the hepatic artery.
      Therefore, embolisation of the hepatic artery can lead to selective necrosis of
      the liver tumour while it may leave normal parenchyma virtually unaffected.
      OBJECTIVES: To study the beneficial and harmful effects of transarterial
      (chemo)embolisation compared with no intervention or placebo intervention in
      patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato
      Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled
      Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index
      Expanded, LILACS, and CINAHL up to November 2011. SELECTION CRITERIA: We included
      all randomised clinical trials assessing beneficial and harmful effects of
      transarterial (chemo)embolisation compared with no intervention or placebo
      intervention in patients with liver metastases, no matter the location of the
      primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information
      on participant characteristics, interventions, study outcome measures, and data
      on the outcome measures for our review as well as information on the design and
      methodology of the studies. Bias risk assessment of the trials, fulfilling the
      inclusion criteria, and data extraction from the retrieved final evaluation
      trials were done by one author and checked by a second author. MAIN RESULTS: One
      randomised clinical trial fulfilled the inclusion criteria of the review. Sixty
      one patients with colorectal liver metastases were randomised into three
      intervention groups: 22 received hepatic artery embolisation, 19 received hepatic
      artery infusion chemotherapy, and 20 were randomised to control, described as "no
      active therapeutic intervention, although symptomatic treatment was provided
      whenever necessary". As hepatic artery infusion chemotherapy is not in the scope
      of this review, we have not included the data from this intervention group. In
      the remaining two groups that were of interest to the review, 43 of the
      participants were men and 18 women. Most tumours were synchronous metastases
      involving up to 75% of the liver and non-resectable. The risk of bias in the
      trial was judged to be high.Patients were followed-up for a minimum of seven
      months. Mortality at last follow-up was 86% (19/22) in the hepatic artery
      embolisation group versus 95% (19/20) in the control group (RR 0.91; 95% CI 0.75
      to 1.1), that is, no statistically significant difference was observed. Median
      survival after trial entry was 7.0 months (range 2 to 44) in the hepatic artery
      embolisation group and 7.9 months (range 1 to 26) in the control group. Nine out
      of 22 (41%) in the hepatic artery embolisation group and five out of 20 (25%) in
      the control group developed evidence of extrahepatic disease (RR 1.64; 95% CI
      0.60 to 4.07). Local recurrence was reported for 10 patients in the trial without
      details about the trial group. Most patients in the embolisation group
      experienced post-embolic syndrome (82%), and one patient had local haematoma. No
      other adverse events were reported. The authors did not report if there were any
      adverse events in the control group. AUTHORS' CONCLUSIONS: On the basis of one
      small randomised trial that did not describe sequence generation, allocation
      concealment or blinding, it can be concluded that in patients with liver
      metastases no significant survival benefit or benefit on extrahepatic recurrence
      was found in the embolisation group in comparison with the palliation group. The
      probability for selective outcome reporting bias in the trial is high. At
      present, transarterial (chemo)embolisation cannot be recommended outside
      randomised clinical trials.

PMID- 22972146
TI  - Medical treatment for small abdominal aortic aneurysms.
AB  - BACKGROUND: Screening for abdominal aortic aneurysm (AAA) in selected groups is
      now performed in England, the USA and Sweden. Patients with aneurysms over 55 mm
      in diameter are generally considered for elective surgical repair. Patients with
      aneurysm diameters below or equal to 55 mm (termed 'small AAAs') are managed with
      aneurysm surveillance as there is currently insufficient evidence to recommend
      surgery in these cases. As more patients are screened, there will be an
      increasing number of small AAAs identified. There is interest in pharmaceutical
      interventions (for example angiotensin converting enzyme (ACE) inhibitors,
      antibiotics, beta-blockers, statins) which could be given to such patients to
      delay or reverse aneurysm expansion and reduce the need for elective surgical
      repair. OBJECTIVES: To assess the effects of medical treatment on the expansion
      rate of small abdominal aortic aneurysms. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator searched the Specialised
      Register (May 2012) and CENTRAL (2012, Issue 5). Clinical trials databases were
      searched for details of ongoing or unpublished studies. The reference lists of
      articles retrieved by electronic searches were searched for additional citations.
      SELECTION CRITERIA: We selected randomised trials in which patients with small
      AAAs allocated to medical treatment with the intention of retarding aneurysm
      expansion were compared to patients allocated to a placebo treatment, alternative
      medical treatment, a different regimen of the same drug or imaging surveillance
      alone. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data
      and assessed the risk of bias in the trials. Meta-analyses were used when
      heterogeneity was considered low. The two primary outcomes were the mean
      difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to
      compare the number of individuals referred to AAA surgery in each group over the
      trial period. MAIN RESULTS: Seven trials involving 1558 participants were
      included in this review; 457 were involved in four trials of antibiotic
      medication, and 1101 were involved in three trials of beta-blocker medication.
      Five of the studies were rated at a high risk of bias.Individually, all of the
      included trials reported non-significant differences in AAA expansion rates
      between their intervention and control groups.The two major drug groups were then
      analysed separately. For AAA expansion it was only possible to combine two of the
      antibiotic trials in a meta-analysis. This demonstrated that roxithromycin had a
      small but significant protective effect (MD -0.86 mm; 95% confidence interval
      (CI) -1.57 to -0.14). When referral to AAA surgery was compared (including all
      four antibiotic trials in the meta-analysis), non-significantly fewer patients
      were referred in the intervention groups (OR 0.96; 95% CI 0.59 to 1.57) than the
      control groups. When only the trials reporting actual elective surgery were
      included in a subgroup analysis, the result remained statistically non
      significant (OR 1.17; 95% CI 0.57 to 2.42).For the beta-blocker trials, when all
      were combined in a meta-analysis, there was a very small, non-significant
      protective effect for propranolol on AAA expansion (MD -0.08 mm; 95% CI -0.25 to
      0.10), and non-significantly fewer patients were referred to AAA surgery in the
      propranolol group (OR 0.74; 95% CI 0.52 to 1.05). Bronchospasm and shortness of
      breath were the main adverse effects from the beta-blockers. In one trial the
      adverse effects were reportedly so severe that the trial was stopped early after
      two years. AUTHORS' CONCLUSIONS: There is some limited evidence that antibiotic
      medication may have a slight protective effect in retarding the expansion rates
      of small AAAs. The quality of the evidence makes it unclear whether this
      translates into fewer referrals to AAA surgery, owing mainly to the small sample
      sizes of the studies.Antibiotics were generally well tolerated with minimal
      adverse effects. Propranolol was poorly tolerated by patients in all of the beta
      blocker trials and demonstrated only minimal and non-significant protective
      effects. Further research on beta-blockers for AAA needs to consider the use of
      drugs other than propranolol.In general, there is surprisingly little high
      quality evidence on medical treatment for small AAAs, especially in relation to
      the use of newer beta-blockers, ACE inhibitors and statins.

PMID- 22972147
TI  - Motivational interviewing for improving outcomes in youth living with HIV.
AB  - BACKGROUND: Almost half of all the new HIV infections occur in youth.
      Motivational interviewing (MI) is a counselling technique that is effective in
      bringing about positive behavior changes in the general population. It is unclear
      whether it can be used to improve outcomes in youth living with HIV. OBJECTIVES:
      To determine whether MI is effective in improving outcomes in youth living with
      HIV. SEARCH METHODS: We used a comprehensive and exhaustive strategy in an
      attempt to identify all relevant studies, regardless of language or publication
      status, in electronic databases (PubMed, the Cochrane Central Register of
      Controlled Trials, EMBASE, LILACS, CINAHL, PsycINFO), conference proceedings and
      specialised databases from January 1980 to March 2012. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) in which youth (aged 10 to 24) living with
      HIV received MI, singly or in combination with another intervention compared to
      any other intervention, and reporting on the outcomes of interest (adherence to
      medication, mortality, quality of life, viral load, CD4-positive-T-lymphocyte
      count, progression to AIDS, retention in care, substance abuse and condom use).
      All settings were considered. DATA COLLECTION AND ANALYSIS: We identified 863
      references.Two authors independently examined the titles and abstracts of all
      identified trials, of which 28 full-text articles were closely screened for
      eligibility based on criteria established a-priori. The included studies were
      appraised for quality in duplicate. Data were extracted using a pre-tested and
      standardised form. No meta-analyses were performed. MAIN RESULTS: Two trials
      located in the United States, reported in four papers met our inclusion criteria.
      They enrolled a total of 237 participants and compared motivational interviewing
      singly to standard of care. None of these trials reported on adherence to HIV
      medication, mortality or quality of life. Both trials reported reductions in
      viral load (in the short term) and unprotected sexual acts. A reduction in
      alcohol use was identified only in one of two studies that reported on this
      outcome. One trial reported on retention. Retention rates were not affected by
      the intervention. AUTHORS' CONCLUSIONS: There is moderate quality evidence,
      coming from two trials which suggests that MI is effective in reducing short term
      viral load and unprotected sexual acts. There is moderate quality evidence from
      one trial that MI is effective in reducing alcohol use. There is a need for more
      trials which report on outcomes such as adherence to medication, mortality and
      quality of life in youth.

PMID- 22972148
TI  - Pharmacological interventions for promoting smoking cessation during pregnancy.
AB  - BACKGROUND: Smoking in pregnancy is a substantial public health problem. When
      used by non-pregnant smokers, pharmacotherapies [nicotine replacement therapy
      (NRT), bupropion and varenicline] are effective treatments for smoking cessation,
      however, their efficacy and safety in pregnancy remains unknown. OBJECTIVES: To
      determine the efficacy and safety of smoking cessation pharmacotherapies,
      including NRT, varenicline and bupropion (or any other medications) when used to
      support smoking cessation in pregnancy. SEARCH METHODS: We searched the Pregnancy
      and Childbirth Group's Trials Register (5 March 2012), checked references of
      retrieved studies and contacted authors in the field. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) with designs that permit the independent
      effects of any type of NRT (e.g. patch, gum etc.) or any other pharmacotherapy on
      smoking cessation to be ascertained were eligible for inclusion. Trials must
      provide very similar (ideally identical) levels of behavioural support or
      cognitive behaviour therapy (CBT) to participants in active drug and comparator
      trial arms.The following RCT designs are considered acceptable.Placebo RCTs: any
      form of NRT or other pharmacotherapy, with or without behavioural support/CBT, or
      brief advice compared with placebo NRT and additional support of similar
      intensity.RCTs providing a comparison between i) behavioural support/CBT or brief
      advice and ii) any form of NRT or other pharmacotherapy added to behavioural
      support of similar (ideally identical) intensity.Parallel- or cluster-randomised
      design trials are eligible for inclusion. However, quasi-randomised, cross-over
      and within-participant designs are not eligible for inclusion due to the
      potential biases associated with these designs. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed trials for inclusion and risk of bias and
      extracted data. Two assessors independently extracted data and cross checked
      individual outcomes of this process to ensure accuracy. The primary efficacy
      outcome was smoking cessation in later pregnancy (in all but one trial, at or
      around delivery); safety was assessed by seven birth outcomes that indicated
      neonatal well being and we also collated data on adherence. MAIN RESULTS: Six
      trials of NRT enrolling 1745 pregnant smokers were included; we found no trials
      of varenicline or bupropion. No statistically significant difference was seen for
      smoking cessation in later pregnancy after using NRT as compared to control (risk
      ratio (RR) 1.33, 95% confidence interval (CI) 0.93 to 1.91, six studies, 1745
      women). Subgroup analysis comparing placebo-RCTs with those which did not use
      placebos found that efficacy estimates for cessation varied with trial design
      (placebo RCTs, RR 1.20, 95% CI 0.93 to 1.56, four studies, 1524 women; non
      placebo RCTs, RR 7.81, 95% CI 1.51 to 40.35, two studies, 221 women; P value for
      random-effects subgroup interaction test = 0.03). There were no statistically
      significant differences in rates of miscarriage, stillbirth, premature birth,
      birthweight, low birthweight, admissions to neonatal intensive care or neonatal
      death between NRT or control groups. AUTHORS' CONCLUSIONS: Nicotine replacement
      therapy is the only pharmacotherapy for smoking cessation that has been tested in
      RCTs conducted in pregnancy. There is insufficient evidence to determine whether
      or not NRT is effective or safe when used to promote smoking cessation in
      pregnancy or to determine whether or not using NRT has positive or negative
      impacts on birth outcomes. Further research evidence of efficacy and safety is
      needed, ideally from placebo-controlled RCTs that investigate higher doses of NRT
      than were tested in the included studies.

PMID- 22972149
TI  - Topical capsaicin (low concentration) for chronic neuropathic pain in adults.
AB  - BACKGROUND: Topical creams with capsaicin are used to treat pain from a wide
      range of chronic conditions including neuropathic pain. Following application to
      the skin capsaicin causes enhanced sensitivity to noxious stimuli, followed by a
      period with reduced sensitivity and, after repeated applications, persistent
      desensitisation. There is uncertainty about the efficacy and tolerability of
      capsaicin for treating painful chronic neuropathies. This is an update of an
      earlier review of topical capsaicin for chronic neuropathic pain in adults that
      looked at all doses and formulations of capsaicin. The original review has now
      been split: here we consider only formulations using a low concentration of
      capsaicin (< 1%) applied several times daily over several weeks, while another
      review will consider a single application of capsaicin at a high concentration.
      OBJECTIVES: To review the evidence from controlled trials on the efficacy and
      tolerability of topically applied low-concentration (< 1%) capsaicin in chronic
      neuropathic pain in adults. SEARCH METHODS: Cochrane CENTRAL, MEDLINE, EMBASE and
      Oxford Pain Relief Database, searched to July 2012. SELECTION CRITERIA:
      Randomised, double-blind, placebo-controlled studies of at least six weeks'
      duration, using low-concentration (< 1%) topical capsaicin to treat neuropathic
      pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      study quality and validity, and extracted data. Information was extracted on
      numbers of participants with pain relief (clinical improvement) after at least
      six weeks, and with local skin reactions, and used to calculate relative risk (or
      risk ratio, RR) and numbers needed to treat to benefit (NNT) and harm (NNH).
      Details of definition of pain relief and specific adverse events were sought.
      MAIN RESULTS: No additional studies were identified for this update of low
      concentration capsaicin. Included studies were published before 1996. Six studies
      (389 participants in total) compared regular application of low dose (0.075%)
      capsaicin cream with placebo cream. There was substantial heterogeneity in
      results, probably as a result of the small number of studies each with small
      numbers of participants, as well as the different pain conditions studied and
      different definitions of "clinical success" reported. Only two studies reported
      data for the preferred primary outcome of at least 50% pain relief, and there
      were too few data for pooled analysis. Local skin reactions were more common with
      capsaicin, usually tolerable, and attenuated with time; the NNH for repeated low
      dose application was 2.5 (95% confidence interval (CI) 2.1 to 3.1). All studies
      satisfied minimum criteria for quality and validity, but maintenance of blinding
      remains a potential problem. AUTHORS' CONCLUSIONS: There were insufficient data
      to draw any conclusions about the efficacy of low-concentration capsaicin cream
      in the treatment of neuropathic pain. The information we have suggests that low
      concentration topical capsaicin is without meaningful effect beyond that found in
      placebo creams; given the potential for bias from small study size, this makes it
      unlikely that low-concentration topical capsaicin has any meaningful use in
      clinical practice. Local skin irritation, which was often mild and transient but
      may lead to withdrawal, was common. Systemic adverse effects were rare.

PMID- 22972150
TI  - Integration of HIV/AIDS services with maternal, neonatal and child health,
      nutrition, and family planning services.
AB  - BACKGROUND: The integration of HIV/AIDS and maternal, neonatal, child health and
      nutrition services (MNCHN), including family planning (FP) is recognized as a key
      strategy to reduce maternal and child mortality and control the HIV/AIDS
      epidemic. However, limited evidence exists on the effectiveness of service
      integration. OBJECTIVES: To evaluate the impact of integrating MNCHN-FP and
      HIV/AIDS services on health, behavioral, and economic outcomes and to identify
      research gaps. SEARCH METHODS: Using the Cochrane Collaboration's validated
      search strategies for identifying reports of HIV interventions, along with
      appropriate keywords and MeSH terms, we searched a range of electronic databases,
      including the Cochrane Central Register of Controlled Trials (CENTRAL),
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE,
      MEDLINE (via PubMed), and Web of Science / Web of Social Science. The date range
      was from 01 January 1990 to 15 October 2010. There were no limits to language.
      SELECTION CRITERIA: Included studies were published in peer-reviewed journals,
      and provided intervention evaluation data (pre-post or multi-arm study
      design).The interventions described were organizational strategies or change,
      process modifications or introductions of technologies aimed at integrating MNCHN
      FP and HIV/AIDS service delivery. DATA COLLECTION AND ANALYSIS: We identified
      10,619 citations from the electronic database searches and 101 citations from
      hand searching, cross-reference searching and interpersonal communication. After
      initial screenings for relevance by pairs of authors working independently, a
      total of 121 full-text articles were obtained for closer examination. MAIN
      RESULTS: Twenty peer-reviewed articles representing 19 interventions met
      inclusion criteria. There were no randomized controlled trials. One study
      utilized a stepped wedge design, while the rest were non-randomized trials,
      cohort studies, time series studies, cross-sectional studies, serial cross
      sectional studies, and before-after studies. It was not possible to perform meta
      analysis. Risk of bias was generally high. We found high between-study
      heterogeneity in terms of intervention types, study objectives, settings and
      designs, and reported outcomes. Most studies integrated FP with HIV testing (n=7)
      or HIV care and treatment (n=4). Overall, HIV and MNCHN-FP service integration
      was found to be feasible across a variety of integration models, settings and
      target populations. Nearly all studies reported positive post-integration effects
      on key outcomes including contraceptive use, antiretroviral therapy initiation in
      pregnancy, HIV testing, and quality of services. AUTHORS' CONCLUSIONS: This
      systematic review's findings show that integrated HIV/AIDS and MNCHN-FP services
      are feasible to implement and show promise towards improving a variety of health
      and behavioral outcomes. However, significant evidence gaps remain. Rigorous
      research comparing outcomes of integrated with non-integrated services, including
      cost, cost-effectiveness, and health outcomes such as HIV and STI incidence,
      morbidity and mortality are greatly needed to inform programs and policy.

PMID- 22972151
TI  - Organocatalytic dynamic kinetic resolution via conjugate addition: synthesis of
      chiral trans-2,5-dialkylcyclohexanones.
AB  - A novel strategy of initiating an organocatalysed dynamic kinetic resolution (dr
      up to 99 : 1 and er up to 94 : 6) for the synthesis of chiral trans-2,5
      dialkylcyclohexanones by an asymmetric conjugate addition of dimethyl malonate on
      to 6-substituted cyclohexenones is reported.

PMID- 22972154
TI  - How do we treat body fat percentages determined by bioelectrical impedance
      analysis?

PMID- 22972153
TI  - Association of body mass index, diabetes, hypertension, and blood pressure levels
      with risk of permanent atrial fibrillation.
AB  - BACKGROUND: After an initial episode of atrial fibrillation (AF), AF may recur
      and become permanent. AF progression is associated with higher morbidity and
      mortality. Understanding the risk factors for permanent AF could help identify
      people who would benefit most from interventions. OBJECTIVE: To determine whether
      body mass index (BMI), diabetes, hypertension, and blood pressure levels are
      associated with permanent AF among people whose initial AF episode terminated.
      DESIGN: Population-based inception cohort study. PARTICIPANTS: Enrollees in Group
      Health, an integrated health care system, aged 30-84 with newly diagnosed AF in
      2001-2004, whose initial AF terminated within 6 months and who had at least 6
      months of subsequent follow-up (N = 1,385). MAIN MEASURES: Clinical
      characteristics were determined from medical records. Permanent AF was determined
      from medical records and ECG and administrative databases. Permanent AF was
      defined as AF present on two separate occasions 6-36 months apart, without any
      documented sinus rhythm between the two occasions. Cox proportional hazards
      models were used to estimate adjusted hazard ratios (HRs). KEY RESULTS: Five-year
      cumulative incidence of permanent AF was 24 %. Compared with normal BMI (18.5
      24.9 kg/m(2)), BMI levels of 25.0-29.9 (overweight), 30.0-34.9 (obese 1), 35.0
      39.9 (obese 2), and >= 40.0 kg/m(2) (obese 3) were associated with HRs of
      permanent AF of 1.26 (95 % CI: 0.92, 1.72); 1.35 (0.96, 1.91); 1.50 (0.97, 2.33);
      and 1.79 (1.13, 2.84), adjusted for age, sex, diabetes, hypertension, blood
      pressure, coronary heart disease, valvular heart disease, heart failure, and
      prior stroke. Diabetes, hypertension, and blood pressure were not associated with
      permanent AF. CONCLUSIONS: For people whose initial AF episode terminates,
      benefits of having lower BMI may include a lower risk of permanent AF. Risk of
      permanent AF was similar for people with and without diabetes or hypertension and
      across blood pressure levels.

PMID- 22972155
TI  - [An accessory spleen as a very rare entity causing a spermatic cord tumor].
AB  - An accessory spleen in the region of the spermatic cord is a very rare entity so
      that preoperative screening with splenic scintigraphy is not indicated.
      Sonographically there will always be the suspicion of a malignant tumor so
      operative exploration of the testes is the therapy of choice. However, it should
      always been borne in mind that such rare entities can occur in the region of the
      spermatic cord and if there is any doubt about the identity of the mass an
      intraoperative rapid section should be performed because in the case of an
      accessory spleen ablation of the testes is not necessary.

PMID- 22972156
TI  - Association of CHKA polymorphism (rs3794186) with alpha-fetoprotein levels in
      hepatocellular carcinoma.
AB  - Choline kinase alpha (CHKA) has been identified to be associated with cancer
      development and progression. In this study, we investigated whether exonic single
      nucleotide polymorphisms (SNPs) of the CHKA gene are associated with
      hepatocellular carcinoma (HCC). Among all SNPs in the 3'-untranslated region
      (UTR), 5'-UTR and the coding region of CHA, only two SNPs (rs3794186 and rs11481)
      in the 3'-UTR had a heterozygosity above 0.1 and a minor allele frequency above
      0.1. Therefore, we selected and assessed these two SNPs (rs3794186 and rs11481)
      in 189 HCC patients and 194 controls. Genetic data were analyzed using the
      SNPAnalyzer Pro, SNPStats and Haploview programs. No SNPs of the CHKA gene were
      found to be associated with the risk of HCC development. Upon analysis of the
      clinical characteristics of HCC, the genotypic frequency of rs3794186 was
      significantly associated with serum alpha-fetoprotein (AFP) levels (P=0.022 in
      the co-dominant 1 model, P=0.0045 in the dominant model and P=0.0052 in the log
      additive model). A significant difference in the allelic frequency of rs3794186
      was also observed between the high AFP (>200 ng/ml) group and the low AFP (<=200
      ng/ml) group [P=0.009, odds ratio (OR) = 0.33, 95% confidence interval (95% CI) =
      0.14-0.75]. The T allele frequency of rs3794186 was lower in the high AFP group
      (6.6%) compared to that in the low AFP group (17.8%). Our results suggest that
      CHKA SNPs (rs3794186 and rs11481) are not associated with HCC development;
      however, rs3794186 may correlate with serum AFP levels in HCC.

PMID- 22972152
TI  - Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous
      cell carcinoma.
AB  - Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene
      with several potential functions, including cell differentiation, cell cycle
      regulation and response to hormones, nickel and stress. The purpose of this study
      was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal
      squamous cell carcinomas searching for its role in the clinical course of these
      tumors. We investigated immunohistochemical expression of NDRG1 protein in 412
      tissue microarray cores of tumor samples from 103 patients with oral and
      oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical
      margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor
      samples, but no expression in any normal tissue sample. Western blot assays
      confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1
      are associated with a high mortality rate. NDRG1 overexpression was related to
      long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph
      node metastasis showed the opposite association with survival (HR = 2.45; p =
      0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor
      role in oral and oropharyngeal squamous cell carcinomas and may be a useful
      marker for these tumors.

PMID- 22972157
TI  - Commentary: Too much sitting--a public health threat?

PMID- 22972158
TI  - Should the measurement of blood pressure in the office be redefined?

PMID- 22972159
TI  - Shooting beyond score:  targeting organ disease to improve risk prediction in
      hypertension.

PMID- 22972160
TI  - Reference blood pressure values in childhood:  an issue to be solved.

PMID- 22972161
TI  - Blood pressure in hospitalized patients:  should we still measure it?

PMID- 22972162
TI  - Future needs in exploration of gene-environment interactions.

PMID- 22972163
TI  - Role of neuroendocrine activation for left ventricular hypertrophy in
      hypertension.

PMID- 22972164
TI  - The effect of sterilization on mechanical properties of soft tissue allografts.
AB  - One major concern regarding soft tissue allograft use in surgical procedures is
      the risk of disease transmission. Current techniques of tissue sterilization,
      such as irradiation have been shown to adversely affect the mechanical properties
      of soft tissues. Grafts processed using Biocleanse processing (a proprietary
      technique developed by Regeneration Technologies to sterilize human tissues) will
      have better biomechanical characteristics than tissues that have been irradiated.
      Fifteen pairs of cadaveric Achilles tendon allografts were obtained and separated
      into three groups of 10 each. Three treatment groups were: Biocleanse,
      Irradiated, and Control (untreated). Each specimen was tested to determine the
      biomechanical properties of the tissue. Specimens were cyclically preloaded and
      then loaded to failure in tension. During testing, load, displacement, and
      optical strain data were captured. Following testing, the cross sectional area of
      the tendons was determined. Tendons in the control group were found to have a
      higher extrinsic stiffness (slope of the load-deformation curve, p = .005), have
      a higher ultimate stress (force/cross sectional area, p = .006) and higher
      ultimate failure load (p = .003) than irradiated grafts. Biocleanse grafts were
      also found to be stiffer than irradiated grafts (p = .014) yet were not found to
      be statistically different from either irradiated or non-irradiated grafts in
      terms of load to failure. Biocleanse processing seems to be a viable alternative
      to irradiation for Achilles tendon allografts sterilization in terms of their
      biomechanical properties.

PMID- 22972165
TI  - Effectiveness of autologous serum as an alternative to fetal bovine serum in
      adipose-derived stem cell engineering.
AB  - In cell culture, medium supplemented with fetal bovine serum is commonly used,
      and it is widely known that fetal bovine serum supplies an adequate environment
      for culture and differentiation of stem cells. Nevertheless, the use of
      xenogeneic serum can cause several problems. We compared the effects of four
      different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and
      adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine
      serum as a control. The stem cells were grafted on nude mice and the in vivo
      differentiation capacity was evaluated. The isolation of adipose-derived stem
      cells was successful irrespective of the culture medium. The proliferation
      potential was statistically significant at passage 2, as follows: 10% autologous
      serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1%
      autologous serum. The differentiation capacity appeared statistically significant
      at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5%
      autologous serum > 2% autologous serum = 1% autologous serum. Ten percent
      autologous serum and 10% fetal bovine serum had greater differentiation capacity
      than 1 and 2% autologous serum in vivo, and no significant difference was
      observed between the groups at >= 5% concentration at 14 weeks. In conclusion,
      10% autologous serum was at least as effective as 10% fetal bovine serum with
      respect to the number of adipose-derived stem cells at the end of both isolation
      and expansion, whereas 1 and 2% autologous serum was inferior.

PMID- 22972166
TI  - Chitosan/bioactive glass nanoparticles composites for biomedical applications.
AB  - Nanocomposite films based on a chitosan blend with bioactive glass nanoparticles
      (BG-NPs) with different formulations, namely SiO(2):CaO:P(2)O(5)(mol.%) = 55:40:5
      and SiO(2):CaO:P(2)O(5):MgO(mol.%) = 64:26:5:5 were produced in order to develop
      systems with applicability in guided tissue regeneration. The zeta (zeta)
      potential of the BG-NPs containing magnesium was found to be lower than the other
      formulation and the corresponding composite with chitosan was the most
      hydrophilic. The bioactive character of the biomaterials was also assessed in
      vitro by immersion of the materials in simulated body fluid, followed by scanning
      electron microscopy (SEM) and energy-dispersive x-ray spectroscopy evaluations.
      SaOs-2 osteoblastic-like cells were seeded on the different nanocomposites and
      their behavior was followed by SEM observations, cytotoxicity assessments, DNA
      quantification and alkaline phosphatase analysis. The introduction of the
      inorganic component in the chitosan matrix had a positive effect on the
      biological response of the membranes. The developed nanocomposite films are
      potential candidates for regenerating damaged bone tissue and could be useful in
      orthopedic and maxillo-facial applications.

PMID- 22972167
TI  - Place of death of pediatric cancer patients in a single institute during 7 years.
AB  - Place of death is an important issue at the end-of-life.  It is poorly understood
      in pediatric cancer patients in Japan. This study aimed  to clarify place of
      death of children with cancer as well as variables associated  with place of
      death.  Study population was pediatric cancer patients who died in the Department
      of  Pediatrics at Kobe University Hospital during the last 7 years. The medical 
      records were retrospectively reviewed regardless of cause of death to derive 
      data relating to patients' characteristics and disease.  18 patients were
      included. Median age at death was 12.2 years old. 6 patients  including 5
      children in complete remission had hematological disease and 12  patients
      suffered from solid tumors.  4 patients (22.2%) died at home, whereas 14 patients
      (77.8%) died in the hospital  including 6 ICU deaths. No one died in hospices.
      Preference of patients was  unavailable due to the lack of inquiry. Factors
      influencing place of death  (home, ICU, non-ICU) were disease (hematological
      disease vs. solid tumor,  p=0.010, brain tumor vs. non-brain tumor, p=0.023),
      disease status (complete  remission vs. non-complete remission, p=0.0014) and
      preference of families  (p=0.029). Among 6 families who expressed preference, no
      disparity was  observed between actual and preferred place of death.  This is the
      first English publication of place of death of pediatric  cancer patients in
      Japan. The low percentage of home death, factors  influencing place of death and
      the lack of disparity between actual and  preferred place of death were
      indicated. Further studies are required to  better understand place of death.

PMID- 22972168
TI  - A study on the selection of DMARDs for the combination therapy  with adalimumab.
AB  - We evaluated whether or not the effect of adalimumab (ADA) in  combination with
      the disease-modifying antirheumatic drugs (DMARDs) other than  methotrexate (MTX)
      is comparable to the ADA+MTX therapy for the treatment of  rheumatoid arthritis
      (RA). A total of 216 patients with active RA at Kohnan  Kakogawa Hospital and
      Kobe University Hospital were enrolled. Clinical and  functional outcomes were
      compared among 4 groups, ADA alone (A group),  ADA + MTX (B group), ADA + MTX +
      other DMARDs (C group), and ADA + other  DMARDs (D group), and the retention
      rates of ADA were evaluated with or  without MTX. CRP was significantly decreased
      from initial measurement at  1 month in all 4 groups, but the continuous efficacy
      with the statistical  significance at all measurement points were observed only
      in combination  with MTX (P<0.05), which was reflected by significantly higher
      retention  rates. Similarly, the disease activities were improved, and
      particularly  the remission rates (DAS28-CRP < 2.3) of A, B and C groups (>42.9%)
      were  higher than that of D group (29.4%) at 2 year. An index of patients' basic 
      activities of daily living, M-HAQ score of A, B and C groups was also better 
      than that of D group. While, looking at the mean changes of M-HAQ from the 
      baseline at 2 years, potential effect of other DMARDs on M-HAQ was  also
      suggested. The results show that ADA + MTX therapy is significantly  superior
      than ADA + other DMARDs in ameliorating RA.

PMID- 22972169
TI  - Detection of tumor markers in prostate cancer and comparison of sensitivity
      between real time and nested PCR.
AB  - The objective of this study is to investigate and compare the sensitivity in
      conventional PCR, quantitative real time PCR, nested PCR and western blots for
      detection of prostate cancer tumor markers using prostate cancer (PCa) cells. We
      performed conventional PCR, quantitative real time PCR, nested PCR, and western
      blots using 5 kinds of PCa cells. Prostate specific antigen (PSA), prostate
      specific membrane antigen (PSMA), and androgen receptor (AR) were compared for
      their detection sensitivity by real time PCR and nested PCR. In real time PCR,
      there was a significant correlation between cell number and the RNA concentration
      obtained (R(2)=0.9944) for PSA, PSMA, and AR. We found it possible to detect
      these markers from a single LNCaP cell in both real time and nested PCR. By
      comparison, nested PCR reached a linear curve in fewer PCR cycles than real time
      PCR, suggesting that nested PCR may offer PCR results more quickly than real time
      PCR. In conclusion, nested PCR may offer tumor maker detection in PCa cells more
      quickly (with fewer PCR cycles) with the same high sensitivity as real time PCR.
      Further study is necessary to establish and evaluate the best tool for PCa tumor
      marker detection.

PMID- 22972170
TI  - Tongue paraesthesia and dysgeusia post suspension laryngoscopy.
AB  - Suspension laryngoscopy is a common laryngeal procedure in Endolaryngeal 
      microsurgery (ELMS). Oral mucosa and dental injuries are the known complications
      of the  procedure. Nerve injury however is an infrequent encounter. We report a
      rare complication  of lingual nerve injury which manifested as tongue numbness
      and altered taste following  Endolaryngeal microsurgery procedure. The condition
      improved completely after few months  of conservative management.

PMID- 22972171
TI  - Identification of unbalanced genome copy number abnormalities in patients with
      multiple myeloma by single-nucleotide polymorphism genotyping microarray
      analysis.
AB  - Single-nucleotide polymorphism genotyping microarray (SNP array) analysis
      provides detailed information on chromosomal copy number aberrations. To obtain
      detailed information on genomic abnormalities related to pathogenesis or
      prognosis of multiple myeloma (MM), we performed 250K SNP array analysis in 39 MM
      patients and 11 cell lines. We identified an accumulation of deletions and
      uniparental disomies at 22q12.1. Among the hyperdiploid MM cases, chromosomal
      imbalance at this locus was associated with poor prognosis. On sequencing, we
      also found a mutation in the seizure-related 6 homolog (mouse)-like (SEZ6L) gene
      located at ch.22q12.1 in an MM cell line, NOP1. We further found isolated
      deletions in 17 genes, five of which are known tumor suppressor genes. Of these,
      deletion of protein tyrosine phosphatase, receptor type D (PTPRD) was found in
      three samples, including two patients. Consistent with previous reports, non
      hyperdiploid MM, deletion of 13q (del13q) and gain of 1q in non-hyperdiploid MMs
      were predictive of poor prognosis (p = 0.039, p = 0.049, and p = 0.013,
      respectively). However, our analysis revealed that unless accompanied by gain of
      1q, the prognosis of non-hyperdiploid MM was as good as that of hyperdiploid MM.
      Thus, SNP array analysis provides significant information useful to understanding
      the pathogenesis and prognosis of MM.

PMID- 22972172
TI  - Pioglitazone enhances small-sized adipocyte proliferation in subcutaneous adipose
      tissue.
AB  - The possibility that mature adipocytes proliferate has not been fully
      investigated.  In this study, we demonstrate that adipocytes can proliferate.  5
      bromo-2'-deoxyuridine (BrdU)-labeled adipocyte like cells, most of which were
      less than 30 MUm in diameter, were observed in adipose tissue.  Proliferating
      cell nuclear antigen (PCNA) was simultaneously detected in BrdU-labeled nuclei. 
      Observation of individual mature adipocytes of smeared specimens on glass slides
      revealed that small sized adipocytes more frequently incorporated BrdU.  Cultured
      mature adipocytes using the ceiling-cultured method showed clustering of
      proliferating cells in small-sized adipocytes.  These small cultured adipocytes,
      but not large ones, extensively incorporated BrdU.  Quantified analysis of BrdU
      incorporation demonstrated that mature visceral adipocytes, including epididymal,
      mesenteric and perirenal adipocytes, proliferated more actively than subcutaneous
      ones.  On the other hand, treatment with pioglitazone (Pio), a ligand of
      peroxisome proliferator-activated receptor gamma, containing food for 2w,
      elevated BrdU incorporation and expression of PCNA in mature adipocytes isolated
      from subcutaneous, but not visceral adipose tissue.  Moreover, Pio induced
      increased BrdU-labeled small-sized subcutaneous adipocytes, which was associated
      with an increased number of total small adipocytes in subcutaneous adipose
      tissue.  In conclusion, mature adipocytes have a subgroup representing the
      potential to replicate, and this proliferation is more active in visceral
      adipocytes.  Treatment with Pio increases proliferation in subcutaneous
      adipocytes.  These results may explain the mechanism of Pio-induced hyperplasia
      especially in subcutaneous adipocytes.

PMID- 22972173
TI  - [Counterfeiting of eye drops?: a laboratory study of antibiotic eye drops
      purchased in two African countries].
AB  - INTRODUCTION: Counterfeit drugs are often ineffective and are considered a
      problem with an immense risk potential especially in the treatment of infectious
      diseases. Emerging and developing countries are particularly affected. Little is
      known about the extent of counterfeit antibiotic drugs used in eye care. In the
      present study we investigated antibiotic eye drops purchased in two African
      countries with respect to the active substance and its concentration in the
      sample. METHODS: A total of 33 antibiotic eye drops purchased in Kenya and the
      Democratic Republic of Congo were tested. The bottles were labeled to contain one
      of the following substances: the quinolones ciprofloxacin, levofloxacin and
      ofloxacin and the aminoglycosides gentamicin and tobramycin. Imported quality
      products as well as cheaper generic drugs were tested. Fluoroquinolones were
      determined by high pressure liquid chromatography (HPLC) and quantified by
      fluorescence measurement and aminoglycosides were tested by using a fluorescence
      polarization immunoassay. RESULTS: All samples were found to contain the declared
      drug. Nine samples (27%) showed an under-concentration by 10% or less and ten
      (30%) showed an increased concentration of 10% or more than indicated on the
      label. 75% of the original drugs but only 12% of the generic drugs had measured
      concentrations within the standard advisory ranges of +/- 5% from the nominal
      value. CONCLUSION: Our results provide no evidence for significant criminal
      counterfeiting of eye drops in the studied countries. The frequent deviation from
      the stated concentration in the generic samples is cause for concern and
      justifies further investigation.

PMID- 22972174
TI  - [Extraconal solitary fibrous tumor of the orbit].
AB  - Solitary fibrous tumors (SFT) are rare spindle cell neoplasms derived from
      specialized fibroblasts. This tumor was first described in the pleura and later
      in the whole body including the orbit. Although an SFT is generally a benign
      tumor malignant transformation and metastasization have also been observed in a
      few cases. Complete excision is the therapy of choice. Here we report on a 50
      year-old male patient whose orbital SFT was removed by transconjunctival anterior
      orbitotomy and 1.5 years after the operation the patient is recurrence and
      complaint-free.

PMID- 22972175
TI  - [Ophthalmologic screening history and vision-targeted health status of patients
      suffering from chloroquine maculopathy].
AB  - BACKGROUND: Maculopathy or retinopathy can develop as a side effect of
      chloroquine intake. Despite recommendations for ophthalmologic screening by the
      American Academy of Ophthalmology (AAO) severe toxic retinal damage still occurs.
      This study aims to clarify how maculopathy affects patient quality of life and
      whether it arises only due to non-compliance with screening guidelines. METHODS:
      Patients suffering from chloroquine maculopathy were questioned about the
      ophthalmologic examinations that took place under therapy and completed a German
      version of the 25 item visual function questionnaire (VFQ-25). RESULTS: A total
      of ten female patients were included in the analysis. Weighted visual acuity
      ranged from 0.09 to 0.8. Median composite score of the VFQ-25 was 33.9. All
      patients were periodically screened for ocular toxicity with a median trimestrial
      screening frequency but five patients did not receive all recommended methods of
      examination. There was suspicion of retinal damage in only one patient even
      without the patient reporting complaints. Median time span between onset of
      visual complaints and the cessation of the drug was 12 months. All patients with
      complaints reported a continuing deterioration of vision even after cessation.
      CONCLUSIONS: Chloroquine maculopathy has a major impact on the vision-related
      health status of affected patients, emphasizing the need for its anticipation.
      Although patients were screened even more frequently than recommended by the AAO
      only half were examined properly and nine out of ten patients had a delay in
      diagnosis and in drug cessation. The continuing deterioration of vision even
      after termination of intake further contributes to the severity of the disease.

PMID- 22972176
TI  - [Medical malpractice in ophthalmology].
AB  - BACKGROUND: The increasing number of patients taking action for medical
      malpractice (MM) is a burden for the medical practitioners accused. After the
      assessment through an arbitration committee, which is free of cost for the
      patients,a large number of lawsuits can be avoided. Discussion of patient
      complaints and analyzing cases of MM is an important concern for the medical
      community in order to reduce errors in treatment and to contribute to patient
      safety. MATERIAL AND METHODS: The patient applications to the arbitration
      committee of the medical association of North-Rhine ("Gutachterkommission
      Nordrhein") for review of MM in the field of ophthalmology in the years 1999-2010
      were analyzed statistically. RESULTS: In the years 1999-2010 a total of 583 cases
      were related to ophthalmology (3% of all cases) and in 122 cases (21%) MM was
      recognized by the committee. In 61% of the cases MM was caused by errors in
      diagnosis, in 24% by errors in processes and in 15% by errors in surgical
      procedures. CONCLUSIONS: The proportion of ophthalmological cases in the total
      number of MM cases is low. Most errors in diagnosis are caused by the lack of
      basic diagnostic on examination procedures. Errors in processes are caused by
      instrumental errors and deficient communication. An important reason for errors
      in surgical procedures is a deficient management of complications. A standardized
      workflow of medical examinations and a quality management can help to avoid MM.

PMID- 22972177
TI  - Normal circulating PTH in Saudi healthy individuals with hypovitaminosis D.
AB  - Recent studies in the Middle East have shown an increased incidence of vitamin D
      deficiency across this region of year-round sunlight. There is scarcity of
      information, however, as to the levels of 1,25-dihydroxyvitamin D [1,25(OH)2D],
      the active form of vitamin D, and its associations with cardiometabolic
      parameters in an Arab cohort and this study aims to fill this gap. In a cross
      sectional study, 33 male and 43 female (22 children and 54 adults, total 76)
      Saudis with previously established low levels of serum 25-hydroxyvitamin D
      [25(OH)D] (<50 ng/ml or 20 nmol/l) were recruited. Anthropometrics were obtained
      and fasting blood samples were taken for a routine measurement of glucose, lipid
      profile, calcium, and albumin, while serum 25(OH)D, 1,25-(OH)2D, and intact PTH
      were quantified using specific ELISAs. Serum calcium, intact PTH, and 1,25(OH)2D
      were all within the normal range in both children and adults in both genders. In
      all subjects, serum 1,25(OH)2D was not associated with intact PTH, while
      circulating 1,25(OH)D inversely correlated with systolic blood pressure (p=0.01)
      and waist circumference (p=0.04). Thus, vitamin D deficient Saudi children and
      adults with normal levels of 1,25-(OH)2D also had normal circulating calcium and
      PTH. This study suggests that local cutoffs should be set that will be of
      clinical significance in the identification of those at true risk for harder end
      points, such as secondary hyperparathyroidism and bone-related diseases.

PMID- 22972178
TI  - GH and cortisol responses following an acute session of respiratory muscle
      endurance training in severely obese patients.
AB  - It is well established that obese patients are hypo-responsive to classical GH
      releasing stimuli, including aerobic exercise. Recently, we have demonstrated
      that whole body vibration was able to markedly stimulate GH secretion in obese
      patients, thus suggesting that this refractoriness is not absolute but dependent
      on the GH-releasing stimulus. Furthermore, we have shown the ability of a
      respiratory muscle endurance training (RMET) to stimulate GH and cortisol
      secretion in healthy subjects. The objective of this study was to evaluate the
      effects of RMET on GH and cortisol responses in severely obese patients. Eight
      severely obese patients (4 M/4 F, mean age+/-SEM: 22.8+/-1.6 years, body mass
      index, BMI: 39.9+/-1.1 kg/m2) underwent an incremental progressive RMET protocol
      of 11 daily sessions, obtained through the use of a specifically designed
      respiratory device (Spiro Tiger(r)). The 12th session of RMET (15 min duration: 1
      min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34
      acts/min, 4 min at 36 acts/min) was associated with blood samplings for
      determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched
      normal-weighted control group (n=7, 4 M/3 F, age: 26.1+/-3.1 years, BMI: 22.4+/
      0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese
      patients, GH secretion significantly increased after a 15-min RMET session.
      Although serum GH levels at 30 min were higher in normal-weighted subjects than
      in obese patients, there was no statistically significant difference in either GH
      peaks or net GH areas under the curve between the 2 groups. RMET significantly
      increased serum cortisol levels in normal-weighted subjects, but was associated
      to a progressive cortisol decline in obese patients. RMET stimulated LA
      production, with no significant differences in normal-weighted subjects and in
      obese patients. A 15-min RMET session was capable to induce a GH response in
      severely obese patients, which was comparable to that recorded in normal-weighted
      subjects. A progressive decline in serum cortisol levels occurred in obese
      patients after RMET, while an opposite pattern (i. e., a significant cortisol
      increase) was found in normal-weighted subjects. Optimization of long-term RMET
      protocols could represent a valid strategy to (physiologically) stimulate GH/IGF
      I system in those GH hyposecretory states such as obesity.

PMID- 22972179
TI  - Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses
      protein synthesis through inhibition of mTORC1 signaling.
AB  - The molecular mechanisms by which cellular energy status regulates global protein
      synthesis in mammary epithelial cells have not been characterized. The objective
      of this study was to examine the effect of AMP-activated protein kinase (AMPK)
      activation by 2-deoxyglucose on protein synthesis and the mammalian target of
      rapamycin complex 1 (mTORC1) signaling pathway in bovine mammary epithelial
      cells. Phosphorylation of AMPK at Thr172 increased by 1.4-fold within 5 min, and
      remained elevated throughout a 30-min time course, in response to 2-deoxyglucose.
      Global rates of protein synthesis declined by 78% of control values. The decline
      in protein synthesis was associated with repression of mTORC1 signaling, as
      indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E
      binding protein-1 (4E-BP1). Phosphorylation of ER-stress marker eIF2alpha was
      also increased but only at 30 min of 2-deoxyglucose exposure. 2-Deoxyglucose
      increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK
      consensus sites but did not change the amount of TSC1 bound to TSC2. Activation
      of AMPK did not result in changes in the amount of raptor bound to mTOR. The
      inhibitory effects of AMPK activation on mTORC1 signaling were associated with a
      marked increase in Ser792 phosphorylation on raptor. Collectively, the results
      suggest that activation of AMPK represses global protein synthesis in mammary
      epithelial cells through inhibition of mTORC1 signaling.

PMID- 22972180
TI  - Efficacy and safety of switching from basal insulin to sitagliptin in Japanese
      type 2 diabetes patients.
AB  - Basal-supported oral therapy (BOT) is often used to treat poorly controlled type
      2 diabetes. However, patients sometimes experience nocturnal and early morning
      hypoglycemia. Thus, maintaining targeted glycemic control by BOT is limited in
      some patients. We assessed the efficacy and safety of replacing basal insulin by
      sitagliptin therapy in Japanese type 2 diabetes patients on BOT. Forty-nine
      subjects were sequentially recruited for the 52-week, prospective, single arm
      study. Patients on BOT therapy were switched from basal insulin to sitagliptin.
      The primary endpoint was change in HbA1c in 52 weeks. The secondary endpoints
      were dropout rate, changes in body weight, frequency of hypoglycemia, and
      relationship between change in HbA1c and insulin secretion capacity evaluated by
      glucagon loading test. The average dose of basal insulin was 15.0+/-8.4 units.
      Sixteen subjects (31.3%) were dropped because replacement by sitagliptin was less
      effective for glycemic control. In these subjects, diabetes duration was longer,
      FPG and HbA1c at baseline were higher, and insulin secretion capacity was lower.
      Change in HbA1c in 52 weeks was - 4 mmol/mol (95% CI - 5 to - 4 mmol/mol)
      (p<0.05). Change in body weight was - 0.71 kg (95% CI - 1.42 to - 0.004 kg)
      (p<0.05). Frequency of hypoglycemia was decreased from 1.21+/-1.05 to 0.06+/-0.24
      times/month. HbA1c level was improved if C-peptide index (CPI) was over 1.19. In
      conclusion, basal insulin in BOT can be replaced by sitagliptin with a decrease
      in HbA1c level and frequency of hypoglycemia in cases where insulin secretion
      capacity was sufficiently preserved.

PMID- 22972181
TI  - HLA-A2 phenotype may be protective against Graves' disease but not against
      Hashimoto's thyroiditis in Caucasians.
AB  - Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the most common
      autoimmune thyroid diseases (AITDs) affecting up to 5% of the general population.
      In Caucasians HT has a prevalence of up to 4.60% and GD a prevalence of 1-2%. The
      aim of this study was to investigate the association between HLA-A2 and the AITDs
      GD and HT among Caucasians. HLA alleles of 33 patients with GD and 75 patients
      with HT were determined by serological typing. The frequency of HLA A2 was
      significantly reduced in GD (p=0.033) but not in HT (p=n.s.) as compared to
      control samples. In individuals positive for HLA-A2 odds ratio for protection
      from GD was found to be 2.8. This study supports the hypothesis that genetic
      predisposition to GD is not restricted to MHC class II molecules. The significant
      negative association between HLA A2 and GD supports the hypothesis that MHC class
      I genes may be relevant for the protection from GD. In contrast the
      nonsignificant results for HT indicate that this association may not apply to
      AITDs in general.

PMID- 22972182
TI  - Effect of physical training on the adipose tissue of diet-induced obesity mice:
      interaction between reactive oxygen species and lipolysis.
AB  - It is well known that high-fat diets (HFDs) induce obesity and result in an
      increase in oxidative stress in adipose tissue, which leads to an impairment of
      fat mobilization by a downregulation of the lipases, such as hormone-sensitive
      lipase (HSL) and adipose triglyceride lipase (ATGL). On the other hand, exercise
      training leads to a reduction in adipose tissue and an improvement of antioxidant
      status and the lipolytic pathway. Our aim was to examine the influence of
      exercise and moderate intensity training on oxidative stress parameters and the
      relationship between the proteins involved in the lipolysis of animals subjected
      to a high-fat fed diet. Twenty-four mice were used and divided into 4 groups
      (n=6): standard diet (SD); standard diet plus exercise (SD+Ex); high-fat diet
      (HFD); and high-fat diet plus exercise (HFD+Ex). The animals received HFD for 90
      days and submitted to a daily training protocol in swinging. The animals were
      euthanized 48 h after the last session of exercise. White adipose tissue
      epididymal fat was excised for the measurement of oxidative stress parameters and
      protein levels of lipolytic enzymes by Western blotting. The results show an
      increase in body weight after 90 days of HFD, and exercise training prevented
      great gain. In adipose tissue, lipid peroxidation and protein carbonylation
      increased after HFD and decreased significantly after exercise training. The
      protein level of CGI-58 was reduced, and FAS was increased in the HFD than in SD,
      whereas ATGL exhibited an increase (p<0.05) in HFD than in SD. The exercise plays
      a significant role in reducing oxidative damage, along with the regulation of
      proteins that are involved in the lipolysis of animals exposed to HFD.

PMID- 22972183
TI  - Graphene as an anti-permeation and protective layer for indium-free transparent
      electrodes.
AB  - We show that graphene can be used as a protective layer for transparent
      electrodes made of materials which would otherwise deteriorate when exposed to
      the environment. In particular, we investigate aluminum-doped zinc oxides and
      ultrathin copper films capped with a one-atom graphene layer in damp heat (95%
      relative humidity and 95  degrees C) and high temperature (up to 180  degrees C)
      conditions. The results clearly indicate that a graphene layer can strongly
      reduce degradation of the electrodes' electrical, optical properties and surface
      morphology, thus preserving the functionality of the transparent electrodes. The
      proposed technique is particularly suitable for flexible optoelectronic devices
      thanks to the mechanical strength of graphene when subjected to bending.

PMID- 22972184
TI  - B-box and SPRY domain containing protein (BSPRY) is associated with the
      maintenance of mouse embryonic stem cell pluripotency and early embryonic
      development.
AB  - Mouse embryonic stem (ES) cells consist of heterogeneous populations with
      differing abilities to proliferate and differentiate. We previously demonstrated
      that the expression level of platelet endothelial cell adhesion molecule 1
      (PECAM1)/CD31 was positively correlated with the undifferentiated state of mouse
      ES cells. In order to screen for a novel gene(s) involved in ES cell
      pluripotency, we performed an oligo microarray analysis and identified that B-box
      and SPRY domain containing protein (BSPRY) was expressed at high levels in PECAM1
      positive cells. Two splice isoforms of BSPRY, BSPRY-1 and BSPRY-2, were expressed
      in undifferentiated ES cells and in blastocysts. Knockdown of BSPRY-1/2 in ES
      cells significantly reduced the number of undifferentiated colonies and caused
      increased expression of primitive ectoderm marker gene Fgf5. The overexpression
      of BSPRY-2 reciprocally increased the number of undifferentiated ES cells in the
      presence of LIF. Similarly, injection of BSPRY-1/2 siRNAs into 2-cell embryos
      caused developmental retardation and degeneration of embryos, and a significant
      decrease in the number of cells, especially in the inner cell mass (ICM), was
      observed at the blastocyst stage. Furthermore, microinjection of a BSPRY-1
      expression vector into pronuclear stage embryos resulted in an increase in the
      hatching blastocysts rate after 120 h of culture. These results suggest that
      BSPRY-1 and BSPRY-2 are associated with both ES cell pluripotency and early
      embryonic development.

PMID- 22972185
TI  - Central administration of neurokinin B activates kisspeptin/NKB neurons in the
      arcuate nucleus and stimulates luteinizing hormone secretion in ewes during the
      non-breeding season.
AB  - Human genetic studies have suggested that kisspeptin and neurokinin B (NKB) play
      pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion.
      However, the role of NKB in this context is less clear compared with that of
      kisspeptin. In the present study, we investigated the ratio of colocalization of
      kisspeptin and NKB in neurons in the arcuate nucleus (ARC), the effects of
      intracerebroventricular infusion of NKB on luteinizing hormone (LH) secretion and
      whether the treatment activates ARC kisspeptin/NKB neurons in seasonally
      anestrous ewes. Double-labeling immunohistochemistry revealed that the majority
      of kisspeptin neurons coexpressed NKB in the ARC. Infusion of NKB for 2 h into
      the lateral ventricle elicited a discharge of LH, which resulted in significant
      increases in LH concentrations between 20 and 50 min after the start of infusion
      compared with a saline-infused control. Animals were sacrificed immediately after
      the end of infusion, and Fos expression in ARC kisspeptin neurons was
      immunohistochemically examined. The NKB treatment activated kisspeptin neurons
      throughout the ARC, and approximately 70% of kisspeptin neurons expressed Fos
      immunoreactivity at the caudal portion of the nucleus. The present study
      demonstrated that a central infusion of NKB elicited a discharge of LH, which was
      associated with the activation of a large population of ARC kisspeptin/NKB
      neurons in seasonally anestrous ewes. The results suggest that NKB plays a
      stimulatory role in the control of pulsatile GnRH secretion and that the
      population of ARC kisspeptin/NKB neurons is one of sites of the NKB action in
      sheep.

PMID- 22972186
TI  - Lysophosphatidic acid action in the bovine corpus luteum -an in vitro study.
AB  - We examined whether the CL is a site for lysophosphatidic acid (LPA) synthesis
      and/or a target for LPA action in the bovine reproductive tract. LPA
      concentrations in the CL tissue increased towards the end of the cycle and were
      stable during early pregnancy. No changes in the expression of LPA receptors
      (LPARs) occurred during the estrous cycle. The expressions of LPAR2 and LPAR4 on
      days 17-19 of pregnancy were higher than those on the respective days of the
      estrous cycle and higher than those on days 8-10 of pregnancy. LPA stimulated P4
      synthesis via 3betaHSD stimulation but did not modulate the interferon-tau
      (IFNtau) influence on P4 synthesis in steroidogenic cells. Moreover, we found LPA
      dependent stimulation of IFNtau action on 2,5'-oligoadenylate synthase (OAS1) and
      ubiquitin-like IFN-stimulated gene 15-kDa protein (ISG15) expression. The present
      study demonstrated that the CL might be a site of LPA synthesis and target of LPA
      action in the bovine reproductive tract. We postulate that during the estrous
      cycle and early pregnancy, LPA exerts autocrine and paracrine effects on the CL
      mainly via LPAR2 and LPAR4. The stimulatory effect of LPA on P4 synthesis via
      3betaHSD stimulation and LPA-dependent stimulation of IFNtau action on OAS1 and
      ISG15 expression suggest that LPA is an additional auxiliary luteosupportive
      factor in steroidogenic cells.

PMID- 22972187
TI  - Polyoxometalate water oxidation catalysts and the production of green fuel.
AB  - In the last five years and currently, research on solar fuels has been intense
      and no sub-area in this field has been more active than the development of water
      oxidation catalysts (WOCs). In this timeframe, a new class of molecular water
      oxidation catalysts based on polyoxometalates have been reported that combine the
      advantages of homogeneous and heterogeneous catalysts. This review addresses
      central issues in green energy generation, the challenges in water oxidation
      catalyst development, and the possible uses of polyoxometalates in green energy
      science.

PMID- 22972188
TI  - Postcranial morphology and the locomotor habits of living and extinct
      carnivorans.
AB  - Members of the order Carnivora display a broad range of locomotor habits,
      including cursorial, scansorial, arboreal, semiaquatic, aquatic, and
      semifossorial species from multiple families. Ecomorphological analyses from
      osteological measurements have been used successfully in prior studies of
      carnivorans and rodents to accurately infer the locomotor habits of extinct
      species. This study uses 20 postcranial measurements that have been shown to be
      effective indicators of locomotor habits in rodents and incorporates an extensive
      sample of over 300 individuals from more than 100 living carnivoran species. We
      performed statistical analyses, including analysis of variance (ANOVA) and
      stepwise discriminant function analysis, using a set of 16 functional indices
      (ratios). Our ANOVA results reveal consistent differences in postcranial skeletal
      morphology among locomotor groups. Cursorial species display distal elongation of
      the limbs, gracile limb elements, and relatively narrow humeral and femoral
      epicondyles. Aquatic and semiaquatic species display relatively robust, shortened
      femora and elongate metatarsals. Semifossorial species display relatively short,
      robust limbs with enlarged muscular attachment sites and elongate claws. Both
      semiaquatic and semifossorial species have relatively elongate olecranon process
      of the ulna and enlarged humeral and femoral epicondyles. Terrestrial,
      scansorial, and arboreal species are characterized by having primarily
      intermediate features, but arboreal species do show relatively elongate manual
      digits. Morphological indices effectively discriminate locomotor groups, with
      cursorial and arboreal species more accurately classified than terrestrial,
      scansorial, or semiaquatic species. Both within and between families, species
      with similar locomotor habits converge toward similar postcranial morphology
      despite their independent evolutionary histories. The discriminant analysis
      worked particularly well to correctly classify members of the Canidae, but not as
      well for members of the Mustelidae or Ursidae. Results are used to infer the
      locomotor habits of extinct carnivorans, including members of several extinct
      families, and also 12 species from the Pleistocene of Rancho La Brea.

PMID- 22972189
TI  - Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is
      associated with worse prognosis.
AB  - Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of
      rapamycin (mTOR) signaling, is overexpressed in and correlates with the
      pathological grade of glioma. However, the potential correlation between GOLPH3
      and clinical outcome in patients with glioblastoma multiforme (GBM) remains
      unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray
      and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue
      from 97 primary GBM patients was examined by tissue microarray and
      immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also
      examined in representative cell lines (U251 and U87) by downregulating GOLPH3
      with RNA interference. For this cohort, the median overall survival (OS) was 12
      months [95 % confidence interval (CI): 10.31-13.69 months], and the median
      progression-free survival (PFS) was 10 months (95 % CI: 7.33-12.67 months).
      Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97,
      41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %).
      Log-rank test showed that patients with low GOLPH3 expression had significantly
      longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p
      = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox
      analysis indicated that GOLPH3 was an independent prognostic factor for OS and
      PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA
      (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines.
      These findings demonstrate that high GOLPH3 expression is associated with poor
      outcome of GBM patients.

PMID- 22972190
TI  - Network science: Luck or reason.

PMID- 22972191
TI  - Restoration of auditory evoked responses by human ES-cell-derived otic
      progenitors.
AB  - Deafness is a condition with a high prevalence worldwide, produced primarily by
      the loss of the sensory hair cells and their associated spiral ganglion neurons
      (SGNs). Of all the forms of deafness, auditory neuropathy is of particular
      concern. This condition, defined primarily by damage to the SGNs with relative
      preservation of the hair cells, is responsible for a substantial proportion of
      patients with hearing impairment. Although the loss of hair cells can be
      circumvented partially by a cochlear implant, no routine treatment is available
      for sensory neuron loss, as poor innervation limits the prospective performance
      of an implant. Using stem cells to recover the damaged sensory circuitry is a
      potential therapeutic strategy. Here we present a protocol to induce
      differentiation from human embryonic stem cells (hESCs) using signals involved in
      the initial specification of the otic placode. We obtained two types of otic
      progenitors able to differentiate in vitro into hair-cell-like cells and auditory
      neurons that display expected electrophysiological properties. Moreover, when
      transplanted into an auditory neuropathy model, otic neuroprogenitors engraft,
      differentiate and significantly improve auditory-evoked response thresholds.
      These results should stimulate further research into the development of a cell
      based therapy for deafness.

PMID- 22972192
TI  - Small heat-shock proteins protect from heat-stroke-associated neurodegeneration.
AB  - Heat stroke is a life-threatening condition, characterized by catastrophic
      collapse of thermoregulation and extreme hyperthermia. In recent years,
      intensification of heat waves has caused a surge of heat-stroke fatalities. The
      mechanisms underlying heat-related pathology are poorly understood. Here we show
      that heat stroke triggers pervasive necrotic cell death and neurodegeneration in
      Caenorhabditis elegans. Preconditioning of animals at a mildly elevated
      temperature strongly protects from heat-induced necrosis. The heat-shock
      transcription factor HSF-1 and the small heat-shock protein HSP-16.1 mediate
      cytoprotection by preconditioning. HSP-16.1 localizes to the Golgi, where it
      functions with the Ca(2+)- and Mn(2+)-transporting ATPase PMR-1 to maintain
      Ca(2+) homeostasis under heat stroke. Preconditioning also suppresses cell death
      inflicted by diverse insults, and protects mammalian neurons from heat
      cytotoxicity. These findings reveal an evolutionarily conserved mechanism that
      defends against diverse necrotic stimuli, and may be relevant to heat stroke and
      other pathological conditions involving necrosis in humans.

PMID- 22972193
TI  - Afternoon rain more likely over drier soils.
AB  - Land surface properties, such as vegetation cover and soil moisture, influence
      the partitioning of radiative energy between latent and sensible heat fluxes in
      daytime hours. During dry periods, soil-water deficit can limit
      evapotranspiration, leading to warmer and drier conditions in the lower
      atmosphere. Soil moisture can influence the development of convective storms
      through such modifications of low-level atmospheric temperature and humidity,
      which in turn feeds back on soil moisture. Yet there is considerable uncertainty
      in how soil moisture affects convective storms across the world, owing to a lack
      of observational evidence and uncertainty in large-scale models. Here we present
      a global-scale observational analysis of the coupling between soil moisture and
      precipitation. We show that across all six continents studied, afternoon rain
      falls preferentially over soils that are relatively dry compared to the
      surrounding area. The signal emerges most clearly in the observations over semi
      arid regions, where surface fluxes are sensitive to soil moisture, and convective
      events are frequent. Mechanistically, our results are consistent with enhanced
      afternoon moist convection driven by increased sensible heat flux over drier
      soils, and/or mesoscale variability in soil moisture. We find no evidence in our
      analysis of a positive feedback--that is, a preference for rain over wetter soils
      at the spatial scale (50-100 kilometres) studied. In contrast, we find that a
      positive feedback of soil moisture on simulated precipitation does dominate in
      six state-of-the-art global weather and climate models--a difference that may
      contribute to excessive simulated droughts in large-scale models.

PMID- 22972194
TI  - Popularity versus similarity in growing networks.
AB  - The principle that 'popularity is attractive' underlies preferential attachment,
      which is a common explanation for the emergence of scaling in growing networks.
      If new connections are made preferentially to more popular nodes, then the
      resulting distribution of the number of connections possessed by nodes follows
      power laws, as observed in many real networks. Preferential attachment has been
      directly validated for some real networks (including the Internet), and can be a
      consequence of different underlying processes based on node fitness, ranking,
      optimization, random walks or duplication. Here we show that popularity is just
      one dimension of attractiveness; another dimension is similarity. We develop a
      framework in which new connections optimize certain trade-offs between popularity
      and similarity, instead of simply preferring popular nodes. The framework has a
      geometric interpretation in which popularity preference emerges from local
      optimization. As opposed to preferential attachment, our optimization framework
      accurately describes the large-scale evolution of technological (the Internet),
      social (trust relationships between people) and biological (Escherichia coli
      metabolic) networks, predicting the probability of new links with high precision.
      The framework that we have developed can thus be used for predicting new links in
      evolving networks, and provides a different perspective on preferential
      attachment as an emergent phenomenon.

PMID- 22972195
TI  - Attention deficits without cortical neuronal deficits.
AB  - The ability to process relevant stimuli selectively is a fundamental function of
      the primate visual system. The best-understood correlate of this function is the
      enhanced response of neurons in the visual cortex to attended stimuli. However,
      recent results show that the superior colliculus (SC), a midbrain structure, also
      has a crucial role in visual attention. It has been assumed that the SC acts
      through the same well-known mechanisms in the visual cortex. Here we tested this
      hypothesis by transiently inactivating the SC during a motion-change-detection
      task and measuring responses in two visual cortical areas. We found that despite
      large deficits in visual attention, the enhanced responses of neurons in the
      visual cortex to attended stimuli were unchanged. These results show that the SC
      contributes to visual attention through mechanisms that are independent of the
      classic effects in the visual cortex, demonstrating that other processes must
      have key roles in visual attention.

PMID- 22972196
TI  - Models of bone metastasis.
AB  - Bone metastases are a common occurrence in several malignancies, including
      breast, prostate, and lung. Once established in bone, tumors are responsible for
      significant morbidity and mortality. Thus, there is a significant need to
      understand the molecular mechanisms controlling the establishment, growth and
      activity of tumors in bone. Several in vivo models have been established to study
      these events and each has specific benefits and limitations. The most commonly
      used model utilizes intracardiac inoculation of tumor cells directly into the
      arterial blood supply of athymic (nude) BalbC mice. This procedure can be applied
      to many different tumor types (including PC-3 prostate cancer, lung carcinoma,
      and mouse mammary fat pad tumors); however, in this manuscript we will focus on
      the breast cancer model, MDA-MB-231. In this model we utilize a highly bone
      selective clone, originally derived in Dr. Mundy's group in San Antonio, that has
      since been transfected for GFP expression and re-cloned by our group. This clone
      is a bone metastatic variant with a high rate of osteotropism and very little
      metastasis to lung, liver, or adrenal glands. While intracardiac injections are
      most commonly used for studies of bone metastasis, in certain instances
      intratibial or mammary fat pad injections are more appropriate. Intracardiac
      injections are typically performed when using human tumor cells with the goal of
      monitoring later stages of metastasis, specifically the ability of cancer cells
      to arrest in bone, survive, proliferate, and establish tumors that develop into
      cancer-induced bone disease. Intratibial injections are performed if focusing on
      the relationship of cancer cells and bone after a tumor has metastasized to bone,
      which correlates roughly to established metastatic bone disease. Neither of these
      models recapitulates early steps in the metastatic process prior to embolism and
      entry of tumor cells into the circulation. If monitoring primary tumor growth or
      metastasis from the primary site to bone, then mammary fat pad inoculations are
      usually preferred; however, very few tumor cell lines will consistently
      metastasize to bone from the primary site, with 4T1 bone-preferential clones, a
      mouse mammary carcinoma, being the exception. This manuscript details inoculation
      procedures and highlights key steps in post inoculation analyses. Specifically,
      it includes cell culture, tumor cell inoculation procedures for intracardiac and
      intratibial inoculations, as well as brief information regarding weekly
      monitoring by x-ray, fluorescence and histomorphometric analyses.

PMID- 22972197
TI  - Cationic galactoporphyrin photosensitisers against UV-B resistant bacteria:
      oxidation of lipids and proteins by 1(O2).
AB  - Antimicrobial photodynamic inactivation is becoming a promising alternative to
      control microbial pathogens. The combination of positively charged groups and
      carbohydrate moieties with porphyrin derivatives results in increased cell
      recognition and water solubility, which improves cell membrane penetration.
      However, the nature of the oxidative damage and the cellular targets of
      photodamage are still not clearly identified. This work reports the use of four
      cationic galactoporphyrins as PSs against two environmental bacteria, Micrococcus
      sp. and Pseudomonas sp., resistant to oxidative stress induced by UV-B exposure.
      The effect of (1)O(2) generated during the PDI assays on oxidation of cellular
      lipids and proteins was also assessed. PDI experiments with Micrococcus sp. and
      Pseudomonas sp. were conducted with 0.5 and 5.0 MUmol L(-1) of photosensitiser,
      respectively, under white light at a fluence rate of 150 mW cm(-2) during 15 min.
      The most effective compounds against Gram (+) bacteria were PSs 3a, 5a and 6a
      leading to ~8.0 log of photoinactivation while PSs 3a and 6a caused the highest
      inactivation (~6.0 log and 5.3 log) of the Gram (-) strain. The adsorption to
      cellular material and (1)O(2) generation capacity of the PS molecule were
      determinant factors for these inactivation profiles. The occurrence of protein
      carbonylation and lipid peroxidation supports the hypothesis that antibacterial
      PDI is triggered by damage of external cell structures such as the cell wall and
      membrane.

PMID- 22972199
TI  - Potential benefit of Bachmann's bundle pacing on left ventricular performance in
      patients with cardiac resynchronized therapy.
AB  - BACKGROUND: Right atrial (RA) appendage (RAA) pacing is reported to impair
      hemodynamic benefits of cardiac resynchronization therapy (CRT) through a
      considerable delay of left atrial (LA) contraction, which compromises appropriate
      balance of atrioventricular (AV) and left ventricular (LV) synchrony. Potential
      usefulness of Bachmann's bundle (BB) pacing to solve the problem remains to be
      confirmed. METHODS AND RESULTS: Atrial synchrony and LV performance was
      investigated by echocardiography in 25 patients undergoing pacemaker implantation
      with preserved AV conduction and LV function (Group I), and 15 patients receiving
      CRT (Group II). In Group I, RAA pacing (AAI mode, n=10) increased P-wave duration
      (PWD) and RA-to-LA contraction delay (IAMD) compared with sinus rhythm (132+/-14
      and 35+/-12 ms vs. 108+/-16 and 13+/-13 ms, P<0.001). The delayed LA contraction
      was associated with early interruption of LV filling, leading to an impairment of
      LV performance (Tei index: 0.43+/-0.12 vs. 0.34+/-0.09, P<0.01). BB pacing (AAI,
      n=15) did not cause such undesirable effects. In Group II, RA (BB)-paced
      biventricular pacing (DDD) reduced PWD and IAMD compared with RA-sensed
      biventricular pacing (VDD) (102+/-14 and -3+/-13 ms vs. 117+/-10 and 21+/-18 ms,
      P<0.001). This restoration of atrial synchrony was associated with significant
      improvement of LV performance (Tei index: 0.56+/-0.18 vs. 0.62+/-0.16, P<0.05).
      CONCLUSIONS: BB pacing preserves atrial synchrony, and might be more favorable
      than RAA pacing for maximizing hemodynamic efficacy of CRT.

PMID- 22972198
TI  - Acute kidney injury following bariatric surgery.
AB  - BACKGROUND: Postoperative acute kidney injury (AKI) following bariatric surgery
      has not been well studied. The aim of this study is to identify factors
      associated with risk of AKI. METHODS: The medical records of adult patients who
      underwent bariatric surgery between March 1, 2005 and March 31, 2011 at the Mayo
      Clinic were reviewed to identify patients who experienced AKI, defined as
      postoperative increase in serum creatinine (sCr) by 0.3 mg/dL within 72 h. For
      each AKI case, two controls were matched for surgical approach (laparotomy vs.
      laparoscopic). A chart review was conducted and conditional logistic regression
      analyses were performed to identify risk factors for AKI. RESULTS: There were
      1,227 patients who underwent bariatric surgery, and of these, 71 developed AKI
      (5.8 %). The median sCr increase was 0.4 (interquartile range 0.3-0.6) mg/dL.
      Independent patient factors associated with increased risk included higher body
      mass index [odds ratio (OR) 1.24, 95 % CI 1.06-1.46 per 5 unit increase, P =
      0.01] and medically treated diabetes mellitus (OR 2.77, 1.36-5.65, P = 0.01).
      Patients experiencing AKI had higher rates of blood transfusions (P < 0.01),
      postsurgical complications (P < 0.01), and longer hospital stays (P < 0.01).
      Another 30 patients developed kidney injury after 72 postoperative hours, usually
      in the setting of dehydration. CONCLUSIONS: Kidney injury following bariatric
      surgery is not uncommon and is associated with higher body mass index and
      diabetes. Further, there should be a high risk of suspicion for kidney injury in
      postoperative patients developing volume depletion.

PMID- 22972200
TI  - Electrophysiological properties of prion-positive cardiac progenitors derived
      from murine embryonic stem cells.
AB  - BACKGROUND: The prion protein (PrP) has been reported to serve as a surface maker
      for isolation of cardiomyogenic progenitors from murine embryonic stem (ES)
      cells. Although PrP-positive cells exhibited automaticity, their
      electrophysiological characteristics remain unresolved. The aim of the present
      study was therefore to investigate the electrophysiological properties of PrP
      positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells.
      METHODS AND RESULTS: Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into
      cardiac progenitors was induced by embryoid body (EB) formation. EBs were
      dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected
      via flow cytometry. Sorted cells were subjected to reverse transcriptase
      polymerase chain reaction, immunostaining and patch-clamp experiments. PrP
      positive cells expressed mRNA of undifferentiation markers, first and second
      heart field markers, and cardiac-specific genes and ion channels, indicating
      their commitment to cardiomyogenic progenitors. PrP-positive cells with
      automaticity showed positive and negative chronotropic responses to isoproterenol
      and carbamylcholine, respectively. Hyperpolarization-activated cation current
      (I(f)) was barely detectable, whereas Na(+) and L-type Ca(2+) channel currents
      were frequently observed. Their spontaneous activity was slowed by inhibition of
      sarcoplasmic reticulum Ca(2+) uptake and release but not by blocking I(f). The
      maximum diastolic potential of their spontaneous firings was more depolarized
      than that of Nkx2.5-GFP-positive cells. CONCLUSIONS: PrP-positive cells contained
      cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP
      can be used as a marker to enrich nascent cardiac progenitors.

PMID- 22972201
TI  - Performance prediction of F1 hybrids between recombinant inbred lines derived
      from two elite maize inbred lines.
AB  - Selection of recombinant inbred lines (RILs) from elite hybrids is a key method
      in maize breeding especially in developing countries. The RILs are normally
      derived by repeated self-pollination and selection. In this study, we first
      investigated the accuracy of different models in predicting the performance of
      F(1) hybrids between RILs derived from two elite maize inbred lines Zong3 and 87
      1, and then compared these models through simulation using a wider range of
      genetic models. Results indicated that appropriate prediction models depended on
      genetic architecture, e.g., combined model using breeding value and genome-wide
      prediction (BV+GWP) has the highest prediction accuracy for high V(D)/V(A) ratio
      (>0.5) traits. Theoretical studies demonstrated that different components of
      genetic variance were captured by different prediction models, which in turn
      explained the accuracy of these models in predicting the F(1) hybrid performance.
      Based on genome-wide prediction model (GWP), 114 untested F(1) hybrids possibly
      having higher grain yield than the original F(1) hybrid Yuyu22 (the single cross
      between Zong3 and 87-1) have been identified and recommended for further field
      test.

PMID- 22972202
TI  - Development of InDel markers for Brassica rapa based on whole-genome re
      sequencing.
AB  - Genome-wide detection of short insertion/deletion length polymorphisms (InDels,
      <5 bp) in Brassica rapa (named the A genome) was performed by comparing whole
      genome re-sequencing data from two B. rapa accessions, L144 and Z16, to the
      reference genome sequence of Chiifu-401-42. In total, we identified 108,558 InDel
      polymorphisms between Chiifu-401-42 and L144, 26,795 InDels between Z16 and
      Chiifu-401-42, and 26,693 InDels between L144 and Z16. From these, 639 InDel
      polymorphisms of 3-5 bp in length between L144 and Z16 were selected for
      experimental validation; 491 (77%) yielded single PCR fragments and showed
      polymorphisms, 7 (1%) did not amplify a product, and 141 (22%) showed no
      polymorphism. For further validation of these intra-specific InDel polymorphisms,
      503 candidates, randomly selected from the 639 InDels, were screened across seven
      accessions representing different B. rapa cultivar groups. Of these assayed
      markers, 387 (77%) were polymorphic, 111 (22%) were not polymorphic and 5 (1%)
      did not amplify a PCR product. Furthermore, we randomly selected 518 InDel
      markers to validate their polymorphism in B. napus (the AC genome) and B. juncea
      (the AB genome), of which more than 90% amplified a PCR product; 132 (25%) showed
      polymorphism between the two B. napus accessions and 41 (8%) between the two B.
      juncea accessions. This set of novel PCR-based InDel markers will be a valuable
      resource for genetic studies and breeding programs in B. rapa.

PMID- 22972204
TI  - Novel poly(hydroxyalkanoates)-based composites containing Bioglass(r) and calcium
      sulfate for bone tissue engineering.
AB  - Three different poly(hydroxyalkanoates) (PHAs), copolymers of poly(3
      hydroxybutyrate) (P3HB), have been used to make composites using two different
      fillers, bioactive glass (type 45S5 Bioglass(r)) and calcium sulfate dihydrate.
      The PHAs used were poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [PHBHV] and two
      copolymers of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [PHBHHx]. The aim of
      the study was the fabrication and characterization of the new composites and the
      assessment of the influence of the particular filler combination on the physical
      properties and bioactivity of the films. The thermal behaviour was studied using
      differential scanning calorimetry while mechanical properties were evaluated
      using dynamic mechanic thermal analysis and tensile strength test. The mechanical
      and thermal properties were affected by particles addition. The distribution of
      the particles in the polymer matrix, observed by scanning electron microscopy,
      was directly related to the mechanical properties. The surface characteristics
      were investigated by contact angle measurements and Raman spectroscopy. The
      extent of formation of hydroxyapatite (HA) upon immersion in simulated body fluid
      (SBF) depended on the polymer used, the amount of fillers employed and the time
      of immersion in SBF. Bioactivity was enhanced in the composites with a rise of
      hydrophilicity. The HA formation was controllable with time in the case of PHBHHx
      composites.

PMID- 22972203
TI  - Phenotypic characterization, genetic mapping and candidate gene analysis of a
      source conferring reduced plant height in sunflower.
AB  - Reduced height germplasm has the potential to increase stem strength,
      standability, and also yields potential of the sunflower crop (Helianthus annuus
      L. var. macrocarpus Ckll.). In this study, we report on the inheritance, mapping,
      phenotypic and molecular characterization of a reduced plant height trait in
      inbred lines derived from the source DDR. This trait is controlled by a
      semidominant allele, Rht1, which maps on linkage group 12 of the sunflower public
      consensus map. Phenotypic effects of this allele include shorter height and
      internode length, insensibility to exogenous gibberellin application, normal
      skotomorphogenetic response, and reduced seed set under self-pollination
      conditions. This later effect presumably is related to the reduced pollen
      viability observed in all DDR-derived lines studied. Rht1 completely cosegregated
      with a haplotype of the HaDella1 gene sequence. This haplotype consists of a
      point mutation converting a leucine residue in a proline within the conserved
      DELLA domain. Taken together, the phenotypic, genetic, and molecular results
      reported here indicate that Rht1 in sunflower likely encodes an altered DELLA
      protein. If the DELPA motif of the HaDELLA1 sequence in the Rht1-encoded protein
      determines by itself the observed reduction in height is a matter that remains to
      be investigated.

PMID- 22972206
TI  - [Development and evaluation of shared medical decision-making scale for end-of
      life patients in Korea].
AB  - PURPOSE: The study was done to develop a shared decision-making scale for end-of
      life patients in Korea. METHODS: The process included construction of a
      conceptual framework, generation of initial items, verification of content
      validity, selection of secondary items, preliminary study, and extraction of
      final items. The participants were 388 adults who lived in one of 3 Korean
      metropolitan cities: Seoul, Daegu, or Busan. Item analysis, factor analysis,
      criterion related validity, and internal consistency were used to analyze the
      data. Data collection was done from July to October 2011. RESULTS: Thirty-four
      items were selected for the final scale, and categorized into 7 factors
      explaining 61.9% of the total variance. The factors were labeled as sharing
      information (9 items), constructing system (7 items), explanation as a duty (5
      items), autonomy (4 items), capturing time (3 items), participation of family (3
      items), and human respect (3 items). The scores for the scale were significantly
      correlated among shared decision-making scale, terminating life support scale,
      and dignified dying scale. Cronbach's alpha coefficient for the 34 items was .94.
      CONCLUSION: The above findings indicate that the shared decision-making scale has
      a good validity and reliability when used for end-of-life patients in Korea.

PMID- 22972205
TI  - Comparison of alpha-synuclein immunoreactivity in the hippocampus between the
      adult and aged beagle dogs.
AB  - Alpha-synuclein (alpha-syn), as a neuroprotein, is expressed in neural tissue,
      and it is related to a synaptic transmission and neuronal plasticity. In this
      study, we compared the distribution and immunoreactivity of alpha-syn and related
      gliosis in hippocampus between young adult (2-3 years) and aged (10-12 years)
      beagle dogs. In both groups, alpha-syn immunoreactivity was detected in neuropil
      of all the hippocampal sub-regions, but not in neuronal somata. In the aged
      hippocampus, alpha-syn immunoreactivity was apparently increased in mossy fibers
      compared to that in the adult dog. In addition, alpha-syn protein level was
      markedly increased in the aged hippocampus. On the other hand, GFAP and Iba-1
      immunoreactivity in astrocytes and microglia, respectively, were increased in all
      the hippocampal sub-regions of the aged group compared to that in the adult
      group: especially, their immunoreactivity was apparently increased around mossy
      fibers. In addition, in this study, we could not find any expression of alpha-syn
      in astrocytes and microglia. These results indicate that alpha-syn
      immunoreactivity apparently increases in the aged hippocampus and that GFAP and
      Iba-1 immunoreactivity are also apparently increased at the regions with
      increased alpha-syn immunoreactivity. This increase in alpha-syn expression might
      be a feature of normal aging.

PMID- 22972207
TI  - [Characteristics of eating behavior in elders with dementia residing in long-term
      care facilities].
AB  - PURPOSE: The purpose of this study was to explore characteristics of eating
      behavior according to level of functional status of elders with dementia (EWD),
      and to examine feeding time, change in food intake and body mass index (BMI)
      according to eating behavior. METHODS: Participants were 149 EWD residing in long
      term care facilities located in Seoul or Gyeonggi province and evaluated using
      the Mini-Mental State Exam-Korean version, Korean version-Activities of Daily
      Living, and Eating Behavior Scale (EBS). Feeding time, change in food intake, and
      BMI were also measured. Data were analyzed using SPSS 17.0, specifically
      descriptive statistics, ANOVA, and Chi-square test. RESULTS: Participants' mean
      EBS score was 10.43+/-6.01 and half of them (54.4%) needed moderate or total
      assistance while eating. The EBS score was significantly lower for elders with
      severe dementia compared to those with mild or moderate dementia; and elders with
      severe ADL dependence compared to those with mild or moderate ADL dependence.
      Lower EBS scores were related to longer feeding time, a greater the rate of
      participants with decreased food intake and 'underweight' BMI. CONCLUSION:
      Nursing intervention programs which are designed for EWD are needed to maintain
      functional eating skills and prevent negative consequences in this population.

PMID- 22972208
TI  - [Effects of antenatal depression and antenatal characteristics of pregnant women
      on birth outcomes: a prospective cohort study].
AB  - PURPOSE: This study was done to evaluate the effects of antenatal depression on
      birth outcomes. METHODS: The participants were 255 pregnant women who were
      followed in a prospective study. Of these, 197 cases were examined included birth
      weight, Apgar scores at 5 minute, premature contraction, complication of labor,
      delivery types and laboratory data. Descriptive statistics, ANOVA, Chi square
      test of linear by linear association, Kruskal Wallis test, Relative Risk,
      univariate and adjusted multiple logistic regression were used for data analysis
      with SPSS/Win. RESULTS: Level of antenatal depression was associated with low
      birth weight (chi2=7.69, p=.010). High risk pregnancy was a predictor of low
      birth weight (OR=6.98 [1.21-40.30]) and baby's weight (OR=2.12, [1.05-4.28]).
      Prepregnancy body mass index (BMI) was a predictor of complications in labor
      (OR=3.59, [1.03-12.48]). But there were no significant effects of antenatal
      depression on other birth outcomes. CONCLUSION: The results of this study
      indicate that women with antenatal depression, high risk pregnancy, prepregnancy
      BMI>=23 kg/M2 should be monitored and managed to ensure favorable birth outcomes.

PMID- 22972209
TI  - [Prerequisite for Korean advance directives: from the view of healthcare
      providers].
AB  - PURPOSE: The purpose of this study was to explore the main prerequisite for
      Korean Advance Directives [KAD] to ensure their better use. METHODS: Data were
      collected from two focus group interviews and individual email responses. Study
      participants were 5 doctors and 6 nurses. All interview data were transcribed and
      analyzed using qualitative content analysis. RESULTS: Three main themes emerged;
      establishing a philosophy of KAD, protocol to practice KAD, and the KAD document
      itself. A philosophy is needed to ensure individual needs, consensus to practice
      AD and identify principle agents. The core of protocol was found to be as
      follows; 1) process, 2) premise, 3) procedure, 4) contextual preparation, 5)
      timing, 6) feasibility. Component and feasibility need to be established for the
      document itself. CONCLUSION: For a positive acceptance of KAD in Korean society,
      a culture sensitive, reality based, and user friendly AD needs to be developed.

PMID- 22972210
TI  - [Depression of married and employed women based on social-role theory].
AB  - PURPOSE: This study was based on social-role theory, and purposes were to
      investigate (1) how depression and health determinants vary with married and
      employed women, and (2) what factors contribute to depression according to family
      cycle. METHODS: A stratified convenience sample of 765 married and employed women
      was recruited during May to August 2010. Study variables of depression, socio
      demographic threatening factors, psycho-stimulating factors, and social-role
      related factors were measured via a structured questionnaire. RESULTS: Prevalence
      rate for depression was 18.6%, with highest rate (25.4%) from elementary
      laborers. Greater levels of depression were related to women's occupation, higher
      life stress, and poorer health; lower social support and vulnerable personality;
      higher levels of social-role related stress. From multivariate analysis, women
      with preadolescents were the most vulnerable to depression affected by
      occupation, life stress, personality, and parenting stress. These factors (except
      for occupational class) combined with economic status, social support, and
      housework unfairness were significant for depression in women with adolescents.
      CONCLUSION: Depression among married and employed women differs by psycho
      stimulating and social role relevant factors in addition to occupational class
      and family life cycle. Female elementary laborers and women with children need to
      have the highest prioritization for community mental health programs.

PMID- 22972211
TI  - [Phenomenology on the lived experience of Korean women with spinal cord
      injuries].
AB  - PURPOSE: The purpose of the study was to understand and explain the essences and
      structures of the experience of Korean women who have had a spinal cord injury.
      METHODS: The data were collected in 2010 through individual in-depth interviews
      using open-ended questions. A total of 9 women with spinal cord injuries
      participated in the study. Each interview lasted about 2 hours. Verbatim
      transcripts were analyzed using phenomenological analysis. RESULTS: Five theme
      clusters emerged from the analysis using Colaizzi's method: frozen mind with
      rigid body; shame due to restrictions of physical function and dependency;
      struggle to go back to the previous normal body; disabilities that are noticeable
      in everyday family life; rebirth by discarding the obsessions of the past. These
      theme clusters illustrate that although most participants faced very strange and
      unbearable situations in most aspects of life after the injury, they were
      empowered finally by finding their hope and by giving new meanings to the current
      existence. CONCLUSION: This study provides deep understanding of women with
      spinal cord injuries who are relatively alienated from society. Based on the
      results of the study, health professionals could develop effective nursing
      interventions to improve quality of life of these women.

PMID- 22972212
TI  - [Impact of prepregnancy body mass index on pregnancy outcome in women with a
      singleton conceived by assisted reproductive technology and spontaneously
      conceived pregnancy: a case-control study].
AB  - PURPOSE: To compare and confirm the impact of prepregnancy body mass index on
      pregnancy outcome in women with a singleton conceived by assisted reproductive
      technology and spontaneously conceived pregnancy. METHODS: A sample of 165 and
      247 pregnant women with and without assisted reproductive technology were
      retrospectively recruited from electronic medical charts of C hospital. RESULTS:
      There were significant differences between the two groups for maternal age,
      paternal age, length of marriage, prepregnancy body mass index, parity,
      spontaneous abortion experience, and preterm delivery. A prepregnancy body mass
      index of >=25 was associated with higher risk for maternal and neonatal
      complication in the assisted reproductive technology group. CONCLUSION: The
      results indicate that a higher prepregnancy body mass index is associated with
      increased risks for adverse pregnancy outcomes for women using assisted
      reproductive technology. So these women need appropriate care to compensate for
      the risk.

PMID- 22972213
TI  - [Effects of a volunteer-run peer support program on health and satisfaction with
      social support of older adults living alone].
AB  - PURPOSE: The purpose of the study was to evaluate effectiveness of a peer support
      program conducted by older community volunteers for older adults living alone.
      METHODS: Thirty volunteers trained as peer supporters were matched with low
      income, older adults living alone in the community on gender. Visits occurred on
      a weekly basis over the 12 month study period, and the volunteers provided peer
      support for health management to solitary older adults. Data were collected,
      before the start of the program and again 6 and 12 months after its
      initialization, from intervention and control groups regarding physical health,
      general health, mental health, depression, social functioning, and satisfaction
      with social support. Repeated measures ANOVA was used to analyze data. RESULTS:
      By the end of the program, socially isolated older adults in the intervention
      group had significantly higher scores in physical health and general health than
      elders in the control group. Significant interaction effects between time and
      group were found for depression, social functioning, and satisfaction with social
      support. CONCLUSION: The peer support program undertaken by older community
      volunteers was effective in improving physical health, general health,
      depression, social functioning, and satisfaction with social support in socially
      isolated, low-income, older adults.

PMID- 22972214
TI  - [A meta-analysis of the variables related to depression in Korean patients with a
      stroke].
AB  - PURPOSE: The purpose of this study was to use meta-analysis to evaluate the
      variables related to depression in patients who have had a stroke. METHODS: The
      materials of this study were based on 16 variables obtained from 26 recent
      studies over a span of 10 years which were selected from doctoral dissertations,
      master's thesis and published articles. RESULTS: Related variables were
      categorized into sixteen variables and six variable groups which included general
      characteristics of the patients, disease characteristics, psychological state,
      physical function, basic needs, and social variables. Also, the classification of
      six defensive and three risk variables group was based on the negative or
      positive effect of depression. The quality of life (ES=-.79) and acceptance of
      disability (ES=-.64) were highly correlated with depression in terms of defensive
      variables. For risk variables, anxiety (ES=.66), stress (ES=.53) showed high
      correlation effect size among the risk variables. CONCLUSION: These findings
      showed that defensive and risk variables were related to depression among stroke
      patients. Psychological interventions and improvement in physical functions
      should be effective in decreasing depression among stroke patients.

PMID- 22972215
TI  - [Validation of a needs assessment tool for case management in Korean medical aid
      beneficiaries].
AB  - PURPOSE: The purpose of this study was to validate the Needs Assessment Tool for
      Case Management (NATCM) for use with Korean medical aid beneficiaries. METHODS:
      Psychometric testing was performed with a sample of 645 Korean medical aid
      beneficiaries, which included 41 beneficiaries who were selected using
      proportional sampling method, to examine intraclass correlation coefficients
      (ICC). Data were evaluated using item analyses, exploratory factor analysis
      (EFA), confirmatory factor analysis (CFA), Cronbach's alpha, and ICC. RESULTS:
      Through psychometric testing the final version of NATCM was found to consist of
      two subscales: 1) Appropriateness of Health Care Utilization (5 items) and 2)
      Self Care Ability (6 items). The two subscale model was validated by CFA
      (RMSEA=.08, GFI=.97, and CFI=.93). Internal consistency measured by Cronbach's
      alpha was .82, and subscale reliability ranged from .79 to .84. The ICC of the
      NATCM between case managers was .73 and between case managers and health care
      professionals. .82. CONCLUSION: This study suggests that the final version of
      NATCM is a brief, reliable, and valid instrument to measure needs of Korean
      medical aid beneficiaries. Therefore, the NATCM can be effectively utilized as an
      important needs assessment as well as outcome evaluation tool for case management
      programs in Korea.

PMID- 22972216
TI  - [Effects of an empowerment program on the adjustment of older adults to nursing
      home life].
AB  - PURPOSE: This study aimed to evaluate the effectiveness of the empowerment
      intervention on the levels of self-esteem, interpersonal relationships and
      adjustment to nursing home life of the Korean nursing home residents. METHODS:
      Participants (n=47) whose period of stay was less than one year were purposefully
      selected from 3 nursing homes in Korea. The experimental group (n=21) attended 10
      weekly hour-long empowerment sessions. The empowerment program comprised two
      components; group education and group discussion. The control group (n=26)
      received a two-hour education about health management. RESULTS: Compared with the
      control group, the experimental group showed significantly higher mean scores of
      self-esteem (t=5.51, p<.001), interpersonal relationships (t=2.73, p=.009) and
      adjustment to nursing home life (t=2.10, p=.041). CONCLUSION: Findings of this
      study suggest that empowerment interventions may be effective in enhancing
      nursing home residents' self-esteem, interpersonal relationships and adjustment
      to nursing home life. Future research is needed to determine if such an
      empowerment program could be used with newly institutionalized elders to speed as
      well as enhance their adjustment to nursing home life.

PMID- 22972217
TI  - [Medication error management climate and perception for system use according to
      construction of medication error prevention system].
AB  - PURPOSE: The purpose of this cross-sectional study was to examine current status
      of IT-based medication error prevention system construction and the relationships
      among system construction, medication error management climate and perception for
      system use. METHODS: The participants were 124 patient safety chief managers
      working for 124 hospitals with over 300 beds in Korea. The characteristics of the
      participants, construction status and perception of systems (electric
      pharmacopoeia, electric drug dosage calculation system, computer-based patient
      safety reporting and bar-code system) and medication error management climate
      were measured in this study. The data were collected between June and August
      2011. Descriptive statistics, partial Pearson correlation and MANCOVA were used
      for data analysis. RESULTS: Electric pharmacopoeia were constructed in 67.7% of
      participating hospitals, computer-based patient safety reporting systems were
      constructed in 50.8%, electric drug dosage calculation systems were in use in
      32.3%. Bar-code systems showed up the lowest construction rate at 16.1% of Korean
      hospitals. Higher rates of construction of IT-based medication error prevention
      systems resulted in greater safety and a more positive error management climate
      prevailed. CONCLUSION: The supportive strategies for improving perception for use
      of IT-based systems would add to system construction, and positive error
      management climate would be more easily promoted.

PMID- 22972218
TI  - [Effects on blood flow velocity, wound healing and pain in hand microsurgery
      patients following heating on non-affected side].
AB  - PURPOSE: The purpose of this study was to identify the effects of heating on the
      non-affected hand on blood flow velocity, wound healing, and pain for hand
      microsurgery patients. METHODS: This study was designed using the nonequivalent
      control group pretest-posttest design. Thirty-nine patients were assigned either
      to the experimental group (20 patients) or control group (19 patients). Data were
      analyzed with chi2-test, Fisher's exact test, t-test, and repeated measure ANOVA
      using SPSS/WIN 17.0 program. RESULTS: After treatment in this program, blood flow
      velocity (F=5.13, p=.008) and wound healing (F=4.11, p=.020) improved
      significantly in the experimental group compared to the control group. But there
      was no significant improvement in pain in the experimental group compared to the
      control group (F=2.40, p=.097). CONCLUSION: Based upon these results, the non
      affected side hand heating was recommended as an independent nursing intervention
      for the patients who need improvement in blood flow velocity and wound healing
      such as patients who have microsurgery. As the heating was effective even when
      applied on the non-affected side, it is the applicable to patients who cannot
      tolerate any therapy on affected side.

PMID- 22972219
TI  - [Factors influencing problem and pathological gambling in participants of horse
      race gambling].
AB  - PURPOSE: The purpose of this study was to examine risk factors for pathological
      gambling of horse race participants. METHODS: The participants, 508 horse race
      gamblers, completed the DSM-IV criteria of pathological gambling, Alcohol Use
      Disorders Identification Test (AUDIT-K) and Symptom Checklist-47-Revision (SCL-47
      R). Data were analyzed using t-test, chi2-test, Fisher's exact test, and logistic
      regression analyses. Behaviors related to horse racing, alcohol abuse, and mental
      health were analyzed between problem or pathological gamblers compared to
      recreational gamblers. RESULTS: The prevalence rates of recreational, problem,
      and pathological gambling were 36.6%, 39.4%, and 24.0%, respectively. Frequency
      of gambling (>=4/day), frequency of racetrack visiting (>=3/month), accompaniment
      (alone), and mental health (SCL-47-R scores) were all associated with increased
      risks of problem and pathological gambling. Expenditure on betting (>=200,000
      won/day) and alcohol abuse (AUDIT-K 8-20 scores) group members had higher levels
      of gambling pathology than recreational gamblers. CONCLUSION: Problem and
      pathological gambling are highly associated with alcohol abuse and mental health
      disorders, suggesting that clinicians should carefully evaluate this population.

PMID- 22972220
TI  - [Effects of a one session spouse-support enhancement childbirth education on
      childbirth self-efficacy and perception of childbirth experience in women and
      their husbands].
AB  - PURPOSE: This study was conducted to evaluate the effect of a one-session spouse
      support enhancement childbirth education on childbirth self-efficacy and
      perception of childbirth experience. METHODS: The design of this study was a
      nonequivalent control group pretest-posttest experiment. The participants in the
      study were 31 couples in the experimental group and 30 in the control group. The
      experimental couples were provided with one session on spouse-support enhancement
      childbirth education the night before delivery. Data were collected at two hours
      after delivery using the Childbirth Self-Efficacy Inventory (CBSEI) and
      perception of childbirth experience scale. Data were analyzed using PASW
      statistics 18 program. Frequencies, percentage, mean, chi2 test, t-test were used
      for data analysis. RESULTS: Childbirth self-efficacy significantly increased in
      the experimental group as compared to the control group, but there was no
      significant difference in perception of childbirth experience in the experimental
      group compared to the control group. CONCLUSION: The results suggest that a one
      session childbirth education has beneficial effects on enhancing childbirth self
      efficacy in pregnant couples. A one-session spouse-support enhancement childbirth
      education is recommended as an effective nursing intervention to promote couple's
      childbirth self-efficacy and it is also recommended that modifications of program
      to promote women's childbirth experience should be considered.

PMID- 22972221
TI  - Implementation of a reference-scaled average bioequivalence approach for highly
      variable generic drug products by the US Food and Drug Administration.
AB  - Highly variable (HV) drugs are defined as those for which within-subject
      variability (%CV) in bioequivalence (BE) measures is 30% or greater. Because of
      this high variability, studies designed to show whether generic HV drugs are
      bioequivalent to their corresponding HV reference drugs may need to enroll large
      numbers of subjects even when the products have no significant mean differences.
      To avoid unnecessary human testing, the US Food and Drug Administration's Office
      of Generic Drugs developed a reference-scaled average bioequivalence (RSABE)
      approach, whereby the BE acceptance limits are scaled to the variability of the
      reference product. For an acceptable RSABE study, an HV generic drug product must
      meet the scaled BE limit and a point estimate constraint. The approach has been
      implemented successfully. To date, the RSABE approach has supported four full
      approvals and one tentative approval of HV generic drug products.

PMID- 22972222
TI  - Factors associated with the glucose-lowering effect of vildagliptin identified
      from the results of the oral glucose tolerance test in Japanese patients with
      type 2 diabetes.
AB  - In order to investigate the factors contributing to the glucose-lowering effect
      of vildagliptin, we analyzed the results of the oral glucose tolerance test
      together with several clinical parameters in Japanese patients with type 2
      diabetes before and after 24 weeks of treatment with vildagliptin.  The data of
      the 13 patients who satisfactorily completed the follow-up examinations were
      included.  After 24 weeks treatment with vildagliptin, the patients were
      classified into a responder group (69.2%) and a non-responder group (30.8%); the
      responders consisting of subjects whose HbA1c decreased following 24 weeks
      treatment with vildagliptin, and the non-responders consisting of subjects who
      did not show any significant decrease of HbA1c.  There were no differences in
      baseline characteristics between the two groups before administration of
      vildagliptin.  After 24 weeks of treatment, HbA1c was significantly reduced from
      7.3 +/- 0.5% to 6.7 +/- 0.5% in the responder group (P = 0.0077), while it tended
      to rather increased from 7.1 +/- 0.6% to 7.5 +/- 0.7% in the non-responder group
      (P = 0.0679).  Also, parameters reflecting the glucose-stimulated insulin
      secretion, such as the insulinogenic index and oral disposition index, were
      significantly higher in the responder group than in the non-responder group,
      whereas insulin sensitivity was similar between the two groups.  These results
      suggest that the difference in the degree of improvement of the glucose tolerance
      between the responder group and non-responder group in this study could be
      associated with the effect of vildagliptin on the glucose-stimulated insulin
      secretion, but not on the insulin sensitivity.

PMID- 22972223
TI  - Tumor size is the strongest predictor of microscopic lymph node metastasis and
      lymph node recurrence of N0 papillary thyroid carcinoma.
AB  - It is well-known that papillary thyroid carcinoma (PTC) frequently metastasizes
      to the regional (central and lateral) lymph nodes, even though it is diagnosed as
      node-negative on preoperative imaging studies.  In this study, we investigated
      predictors of microscopic node metastasis and lymph node recurrence of PTC
      without node metastasis detected preoperatively (N0).  Of the clinicopathological
      features that can be evaluated pre- and intraoperatively, tumor size (> 2 cm) was
      the strongest predictor of microscopic central and lateral node metastasis on
      multivariate logistic analysis.  Also, the tumor size most markedly affected
      lymph node recurrence, but not distant recurrence.  Lymph node recurrence may not
      be immediately life-threatening, but it can be a stressor both for physicians and
      patients.  Therefore, careful lymph node dissection is recommended for PTC with a
      large size, even though it is prophylactic.

PMID- 22972224
TI  - Leprechaunism (Donohue syndrome): a case bearing novel compound heterozygous
      mutations in the insulin receptor gene.
AB  - Leprechaunism (Donohue syndrome) is the most severe type of insulin receptor
      (INSR) gene anomaly with the majority of patients surviving for only 2 years.  We
      report a surviving 2 -year-old male with leprechaunism, bearing novel compound
      heterozygous mutations in the INSR.  The patient is a Japanese boy with
      acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, gum
      hypertrophy and extremely high insulin levels (6702 mU/mL).  He was as having
      identified novel compound heterozygous mutations in INSR (p.T910M and p. E1047K).
      At 24 day-old, recombinant human insulin-like growth factor 1 (rh-IGF1)
      treatment was started because of poor weight gain.  At 2 years old, the patient's
      serum glucose level and HbA1C value had worsened, and both a bolus of rh-IGF-1
      and a subcutaneous injection of a rapid-acting insulin analog after meals, in
      addition to alpha-glycosidase inhibitor, were initiated from 2 years onward. 
      Oxygen administration and biphasic positive airway pressure treatment were also
      initiated from 2 years old due to upper airway obstruction with adenoidal
      hypertrophy.  In the experiments conducted using COS7 cells homozygously
      transfected with the INSR mutation, T910M INSR failed to process the proreceptor
      and decreased insulin-stimulated tyrosine phosphorylation.  E1047K INSR resulted
      in a complete absence of insulin-stimulated tyrosine phosphorylation.  These
      findings suggest the near absence of INSR in this patient.  We consider that the
      rhIGF1 treatment contributed to his long survival, but it was not able to prevent
      his diabetic condition.  Our report provides important insights into the function
      of INSR, and for the treatment of leprechaunism.

PMID- 22972225
TI  - Slip dynamics at a patterned rubber/glass interface during stick-slip motions.
AB  - We report on an experimental study of heterogeneous slip instabilities generated
      during stick-slip motions at a contact interface between a smooth rubber
      substrate and a patterned glass lens. Using a sol-gel process, the glass lens is
      patterned with a lattice of parallel ridges (wavelength, 1.6 MUm, amplitude 0.35
      MUm). Friction experiments using this patterned surface result in the systematic
      occurrence of stick-slip motions over three orders of magnitude in the imposed
      driving velocity while stable friction is achieved with a smooth surface. Using a
      contact imaging method, real-time displacement fields are measured at the surface
      of the rubber substrate. Stick-slip motions are found to involve the localized
      propagation of transverse interface shear cracks whose velocity is observed to be
      remarkably independent on the driving velocity.

PMID- 22972226
TI  - Probability distributions for the run-and-tumble bacterial dynamics: an analogy
      to the Lorentz model.
AB  - In this paper, we exploit an analogy of the run-and-tumble process for bacterial
      motility with the Lorentz model of electron conduction in order to obtain
      analytical results for the intermediate scattering function. This allows to
      obtain an analytical result for the van Hove function in real space for two
      dimensional systems. We furthermore consider the 2D circling motion of bacteria
      close to solid boundaries with tumbling, and show that the analogy to electron
      conduction in a magnetic field allows to predict the effective diffusion
      coefficient of the bacteria. The latter is shown to be reduced by the circling
      motion of the bacteria.

PMID- 22972227
TI  - Crawling motility through the analysis of model locomotors: two case studies.
AB  - We study model locomotors on a substrate, which derive their propulsive
      capabilities from the tangential (viscous or frictional) resistance offered by
      the substrate. Our aim is to develop new tools and insight for future studies of
      cellular motility by crawling and of collective bacterial motion. The purely
      viscous case (worm) is relevant for cellular motility by crawling of individual
      cells. We re-examine some recent results on snail locomotion in order to assess
      the role of finely regulated adhesion mechanisms in crawling motility. Our main
      conclusion is that such regulation, although well documented in several
      biological systems, is not indispensable to accomplish locomotion driven by
      internal deformations, provided that the crawler may execute sufficiently large
      body deformations. Thus, there is no snail theorem. Namely, the crawling analog
      of the scallop theorem of low Reynolds number hydrodynamics does not hold for
      snail-like crawlers. The frictional case is obtained by assuming that the viscous
      coefficient governing tangential resistance forces, which act parallel and in the
      direction opposite to the velocity of the point to which they are applied,
      depends on the normal force acting at that point. We combine these surface
      interactions with inertial effects in order to investigate the mechanisms
      governing the motility of a bristle-robot. This model locomotor is easily
      manufactured and has been proposed as an effective tool to replicate and study
      collective bacterial motility.

PMID- 22972228
TI  - Diblock and triblock copolymer thin films on a substrate with controlled
      selectivity.
AB  - Using self-consistent field theory (SCFT), morphology development in symmetric
      linear ABC triblock copolymer films on neutral and selective substrates has been
      studied, and it is compared with the triblock copolymer morphologies in bulk. In
      particular, the effects of the substrate preferable to B (interior) block on
      nanopattern formation of the copolymer films are of our central interest. Here,
      we report various nanopatterns with tunable square morphologies. The domain
      patterns are much more diverse than those parallel to the substrate with
      substrate selectivity for end-block or those vertical to the substrate without
      substrate selectivity. Furthermore, in order to figure out an economical and
      efficient way to fabricate useful passive pattern transfer layers, which have
      potential applications in microelectronic processes and ultrahigh density storage
      media, we propose a two-step strategy and scrutinize the conditions for
      generating square symmetries using cylinder-forming or lamella-forming AB diblock
      copolymers deposited on substrates created from ABC triblock copolymer films. It
      is found that a thinner film with weak incompatibility can produce square
      patterns.

PMID- 22972229
TI  - Sink or swim: a test of tadpole behavioral responses to predator cues and
      potential alarm pheromones from skin secretions.
AB  - Chemical signaling is a vital mode of communication for most organisms, including
      larval amphibians. However, few studies have determined the identity or source of
      chemical compounds signaling amphibian defensive behaviors, in particular,
      whether alarm pheromones can be actively secreted from tadpoles signaling danger
      to conspecifics. Here we exposed tadpoles of the common toad Bufo bufo and common
      frog Rana temporaria to known cues signaling predation risk and to potential
      alarm pheromones. In both species, an immediate reduction in swimming activity
      extending over an hour was caused by chemical cues from the predator Aeshna
      cyanea (dragonfly larvae) that had been feeding on conspecific tadpoles. However,
      B. bufo tadpoles did not detectably alter their behavior upon exposure to
      potential alarm pheromones, neither to their own skin secretions, nor to the
      abundant predator-defense peptide bradykinin. Thus, chemicals signaling active
      predation had a stronger effect than general alarm secretions of other common
      toad tadpoles. This species may invest in a defensive strategy alternative to
      communication by alarm pheromones, given that Bufonidae are toxic to some
      predators and not known to produce defensive skin peptides. Comparative
      behavioral physiology of amphibian alarm responses may elucidate functional trade
      offs in pheromone production and the evolution of chemical communication.

PMID- 22972230
TI  - Neuropeptide Y-induced feeding is dependent on GABAA receptors in neonatal
      chicks.
AB  - In mammals and birds, neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) are
      found in brain areas known to be involved in the control of ingestive behavior
      and act to increase voluntary food intake. In rats, significant evidence suggest
      a functional and behavioral interaction between NPY and GABA mediated
      transmission in various brain regions, including the arcuate and paraventricular
      nuclei of the hypothalamus which can be important in the regulation of feeding
      behavior. In the present study, the effect of intracerebroventricular (ICV)
      administration of NPY and GABA receptor antagonists on food intake was examined
      in neonatal chicks. The ICV injection of NPY strongly stimulated food intake
      while co-administration of NPY and picrotoxin, a GABA(A) antagonist, (but not
      CGP54626, a GABA(B) antagonist) weakened food intake induced by NPY. These
      results suggest that central NPY stimulates food intake in neonatal chicks by
      interaction with the GABAergic system via GABA(A) receptors.

PMID- 22972231
TI  - Coexpression of three middle wavelength-absorbing visual pigments in sexually
      dimorphic photoreceptors of the butterfly Colias erate.
AB  - The tiered ommatidia of the Eastern Pale Clouded yellow butterfly, Colias erate,
      contain nine photoreceptor cells, four of which contribute their rhabdomeral
      microvilli to the distal tier of the rhabdom. We analyzed the visual pigments and
      spectral sensitivities of these distal photoreceptors in both sexes of Colias
      erate. A subset of photoreceptor cells expresses a newly discovered middle
      wavelength-absorbing opsin, Colias erate Blue (CeB), in addition to two
      previously described middle wavelength-absorbing opsins, CeV1 and CeV2. The other
      photoreceptors either coexpress CeV1 and CeV2, or exclusively express a short
      wavelength-absorbing opsin, CeUV, or a long wavelength-absorbing opsin, CeL.
      Males and females have the same visual pigment expression patterns, but the
      photoreceptor spectral sensitivities are sexually dimorphic. The photoreceptors
      coexpressing three middle wavelength-absorbing opsins are broad-blue receptors in
      males, but in females they are narrow-blue receptors. Those with CeV1 and CeV2
      are violet receptors in females, while they are shouldered-blue receptors in
      males. The sexual dimorphism in spectral sensitivity is caused by a sex-specific
      distribution of fluorescent pigment that functions as a spectral filter.

PMID- 22972232
TI  - Parameters determining the efficacy of adoptive CD8 T-cell therapy of
      cytomegalovirus infection.
AB  - Reactivation of latent cytomegalovirus (CMV) in the transient state of
      immunodeficiency after hematopoietic cell transplantation (HCT) is the most
      frequent and severe viral complication endangering leukemia therapy success. By
      infecting the bone marrow (BM) stroma of the transplantation recipient, CMV can
      directly interfere with BM repopulation by the transplanted donor-derived
      hematopoietic cells and thus delay immune reconstitution of the recipient.
      Cytopathogenic virus spread in tissues can result in CMV disease with multiple
      organ manifestations of which interstitial pneumonia is the most feared. There
      exists a 'window of risk' between hematoablative treatment and reconstitution of
      antiviral immunity after HCT, whereby timely reconstitution of antiviral CD8 T
      cells is a recognized positive prognostic parameter for the control of
      reactivated CMV infection and prevention of CMV disease. Supplementation of
      endogenous reconstitution by adoptive cell transfer of 'ready-to-go' effector
      and/or memory virus epitope-specific CD8 T cells is a therapeutic option to
      bridge the 'window of risk.' Preclinical research in murine models of CMV disease
      has been pivotal by providing 'proof of concept' for a benefit from CD8 T-cell
      therapy of HCT-associated CMV disease (reviewed in Holtappels et al. Med
      Microbiol Immunol 197:125-134, 2008). Here, we give an update of our previous
      review with focus on parameters that determine the efficacy of adoptive
      immunotherapy of CMV infection by antiviral CD8 T cells in the murine model.

PMID- 22972235
TI  - Long-lived platinum(II) diimine complexes with broadband excited-state
      absorption: efficient nonlinear absorbing materials.
AB  - Platinum(II) diimine complexes with naphthalimide substituted fluorenylacetylide
      ligands are synthesized and characterized. The complexes exhibit long-lived
      (3)ILCT or (3)ILCT/(3)MLCT/(3)LLCT excited states (tau = ~20-30 MUs) and
      broadband triplet transient absorption in the visible-NIR region. Nonlinear
      transmission experiments at 532 nm demonstrate that these complexes are efficient
      nonlinear absorbing materials.

PMID- 22972233
TI  - Pore-forming bacterial toxins and antimicrobial peptides as modulators of ADAM
      function.
AB  - Membrane-perturbating proteins and peptides are widespread agents in biology.
      Pore-forming bacterial toxins represent major virulence factors of pathogenic
      microorganisms. Membrane-damaging peptides constitute important antimicrobial
      effectors of innate immunity. Membrane perturbation can incur multiple responses
      in mammalian cells. The present discussion will focus on the interplay between
      membrane-damaging agents and the function of cell-bound metalloproteinases of the
      ADAM family. These transmembrane enzymes have emerged as the major proteinase
      family that mediate the proteolytic release of membrane-associated proteins, a
      process designated as "shedding". They liberate a large spectrum of functionally
      active molecules including inflammatory cytokines, growth factor receptors and
      cell adhesion molecules, thereby regulating such vital cellular functions as cell
      cell adhesion, cell proliferation and cell migration. ADAM activation may
      constitute part of the cellular recovery machinery on the one hand, but likely
      also promotes inflammatory processes on the other. The mechanisms underlying ADAM
      activation and the functional consequences thereof are currently the subject of
      intensive research. Attention here is drawn to the possible involvement of
      purinergic receptors and ceramide generation in the context of ADAM activation
      following membrane perturbation by membrane-active agents.

PMID- 22972236
TI  - Establishment of self-renewing porcine embryonic stem cell-like cells by signal
      inhibition.
AB  - Although the establishment of putative porcine embryonic stem cells (ESCs) has
      been reported, such cell lines quickly lose their self-renewal ability, as they
      easily differentiate or become extinct after only a limited number of passages in
      culture. ESC-like cells exhibiting self-renewal rather than pluripotency are
      considered to be a valuable resource in applications such as drug screening and
      toxicology testing in humans, livestock and veterinary medicine. Here, we report
      the generation of unique cell lines established from the inner cell mass (ICM) of
      porcine embryos by using inhibitors of glycogen synthase kinase 3beta and mitogen
      activated protein kinase kinase 1. These ICM-derived cell lines were initially
      cultured and passaged in conventional ES medium for human ESCs and showed porcine
      ESC-like morphology with alkaline phosphatase (AP) activity. After transfer to
      culture in ES medium containing inhibitors, the morphology of the colonies was
      dramatically changed, i.e., they were closely packed smooth-edged colonies with
      close cell-cell boundaries and showed the expression of undifferentiated markers
      including OCT4 (POU5F1) and NANOG. Notably, the self-renewal capacity and
      morphology of the cells were LIF-dependent, consistent with the expression of LIF
      receptors and phosphorylation of signal transducer and activator of transcription
      3. To date, our established cell lines have been cultured continuously for over
      100 passages without any overt morphological changes. Thus, the established cell
      lines reported here provide a new ESC-like cell culture system for use not only
      in the fields of veterinary medicine and livestock but also human medical
      research, since porcine physiology closely resembles that of humans.

PMID- 22972234
TI  - Host-cell factors involved in papillomavirus entry.
AB  - Papillomaviruses infect skin and mucosa where they induce warts and cancers. For
      entry to occur, they sequentially engage numerous host proteins, allowing them to
      deliver their genetic information into target cells. This multistep process
      starts with initial binding via its L1 major capsid protein, followed by
      structural changes of the capsid on the cell surface, engagement of different
      receptors, and endocytosis. The post-entry phase includes capsid disassembly,
      endosomal escape of a complex of the minor capsid protein L2 and the viral
      genome, its transport into the nucleus, and accumulation at nuclear
      substructures. This review summarizes the current knowledge of the papillomavirus
      entry pathway and the role of cellular proteins involved in this course of
      events.

PMID- 22972237
TI  - Left ventricular mass and oxygen uptake in top handball athletes.
AB  - The key challenge in athlete's screening is the distinction between abnormal and
      normal which is hindered by the fact that the adaptation to sports activity in
      endurance athletes is different to that in power athletes. Especially
      cardiomyopathies provoke changes in ECG and echocardiography (echo) at an early
      stage when clinical symptoms are absent. ECG and echo data and their relationship
      to fitness peculiar to top handball players have never been described. We studied
      291 male first league handball players (32 Olympians/47 national players) (25.3+/
      4.4 years). Check up consisted of ECG, spiroergometry and echocardiography. None
      had T-wave inversions, 3.1% showed early repolarisation abnormalities in the
      precordial leads. Sokolow-Lyon voltage criterion for left ventricular hypertrophy
      was positive in 19.3%. Spiroergometry showed a maximum oxygen uptake (peakVO2) of
      50.3+/-7.7 ml/min/kg body weight. LVmass was increased in comparison to normal
      values. There was a correlation between peakVO2 and LVindex (p<0.001, r=0.341),
      (LVmass/peak VO2 p=0.053, r=0.125). A relationship between cardiac dimensions and
      peakVO2 could not be confirmed. In professional handball players early
      repolarisation abnormalities were less frequent and LVmass was increased when
      compared with soccer players. The need for normal values for different types of
      sports is crucial to guarantee a proper evaluation of athletes.

PMID- 22972238
TI  - Sports injuries in Brazilian blind footballers.
AB  - The purpose of this study was to assess the characteristics and prevalence of
      sports-related injuries in visually disabled athletes of the Brazilian football 5
      a-side team. The participants were 13 male athletes, all classified as B1 visual
      class, members of the Brazilian team, who played in five consecutive
      international competitions. Data were collected using the Brazilian Paralympic
      Committee and the Brazilian Confederation of Sports for the Blind report form.
      From the total of 13 athletes, 11 succumbed to some form of injury during the 5
      competitions, which incorporated 23 matches, representing a prevalence of 84.6%.
      A total of 35 sports injuries were recorded, giving a clinical incidence of 2.7
      injuries per athlete and an injury risk of 0.85 and an incidence rate of 0.12
      injuries per match. Traumatic injuries (80%) were more common than overuse
      injuries (20%) (p<0.05). The highest distribution of injury was in the lower
      limbs (80%), followed by the head (8.6%), spine (5.7%) and upper limbs (5.7%).
      The body regions most affected were the knee (28.6%), feet (17.1%), ankle (11.4%)
      and thigh (11.4%). Contusions (31.4%), sprains (25.7%) and tendinopathy (8.6%)
      were the most frequent diagnoses. This is the first study to describe the nature
      and prevalence of sports-related injuries in 5-a-side football in blind athletes.
      The results are important in guiding strategies to inform the implementation of
      preventive pathways and provide a strong rationale for the compulsory use of
      additional protective equipment.

PMID- 22972239
TI  - Footstep manipulation during uphill running.
AB  - The present study investigated the effects of step frequency manipulation during
      training on slopes (2%) on biomechanical parameters at Iso-Efficiency Speed
      (without increasing the metabolic demand). 24 male marathon runners were randomly
      allocated to one of 2 training groups for 3 weeks: step frequency manipulation
      group (SFM, n=12) and free step frequency group (SFF, n=12). Lower limb kinematic
      parameters were measured before and after the 3 weeks training. The SFM group
      increased step length 4.30% (p<0.001), flight time 29.48% (p<0.001) and decreased
      contact time 14% (p<0.01). These findings coincide with characteristics of better
      running performances. The SFF group did not elicit such results. The results from
      the study could help coaches to devise training methods which could improve an
      athlete's performance through increasing step length. The method provided may aid
      faster race times for athletes.

PMID- 22972240
TI  - The effects of aerobic training and age on plasma sICAM-1.
AB  - Chronic low-grade systemic inflammation plays a role in the development of
      cardiovascular (CV) disease. Habitual endurance exercise training reduces the
      risk of CV disease in part through anti-inflammatory mechanisms. The purpose of
      this study was to investigate the effects of age, endurance training status, and
      their interaction on pro-inflammatory plasma cytokines involved in the
      pathogenesis of CV disease. Subjects were BMI-matched young (25+/-3 years;
      endurance trained: n=9, sedentary: n=11) and older (62+/-5 years; endurance
      trained: n=12, sedentary: n=11) men. Plasma cytokine concentrations were
      determined by multiplex cytometric bead assay. Soluble intercellular adhesion
      molecule-1 (sICAM-1) levels were 40% higher in sedentary older men compared to
      young sedentary subjects (P=0.048), but they were not different between the young
      and older trained men. Furthermore, sICAM-1 levels were negatively correlated
      with maximal oxygen uptake (VO2max; r= - 0.38, P=0.01) across all subjects. There
      were no significant differences among the groups in plasma concentrations of
      monocyte chemoattractant protein-1 (MCP-1), soluble tumor necrosis-alpha receptor
      (sTNFR), soluble CD40 ligand (sCD40L), or resistin. We conclude that habitual
      endurance training is associated with an attenuated age-related increase in
      plasma sICAM-1.

PMID- 22972241
TI  - Radiological abnormalities and low back pain in gymnasts.
AB  - Several studies have shown a higher prevalence of radiological abnormalities
      among gymnasts. However, the types of radiological abnormalities associated with
      low back pain (LBP) have not been clarified. The hypothesis was that significant
      relationships between radiological abnormalities and LBP may be revealed by
      discriminating between the types of MRI abnormalities while considering
      confounding factors. The subjects were 104 Japanese collegiate gymnasts (men, 70;
      women, 34). The presence of LBP was evaluated using the questionnaire developed
      by Osaka City University (OCU Test). Magnetic resonance imaging (MRI)
      abnormalities were evaluated using T1- and T2-weighted MRI. The prevalence of
      more than 1 MRI abnormality in gymnasts was 47.1% (49/104). The chi-square test
      showed that the incidence of lumbar disc degeneration (LDDG) and limbus vertebra
      was significantly greater in gymnasts with LBP than in gymnasts without LBP. By
      using logistic regression analysis to analyze the concomitant environmental
      variables, only LDDG (odds ratio, 2.70; 95% confidence interval, 1.10-6.66) was
      selected as a statistically significant variable accounting for LBP. In
      conclusion, LDDG is a predictor for LBP in Japanese collegiate gymnasts.

PMID- 22972242
TI  - Reliability of maximal lactate-steady-state.
AB  - The aim of this study was the analysis of reliability and day-to-day-variability
      of power (PMLSS), blood lactate concentration (BLCMLSS) and heart rate (HRMLSS)
      in maximal lactate- steady-state during cycle ergometry. 32 male subjects (25+/-3
      years, 180+/-7 cm, 76+/-8 kg) have undergone several constant-load-tests lasting
      30 min to determine 4 PMLSS. During the test, blood-samples were taken from the
      earlobe after 4, 8,10, 14, 18, 22, 26 und 30 min for detecting the BLCMLSS. PMLSS
      was defined as the highest workload that can be maintained without accumulation
      of BLC by more than 0.05 mmol/l/min during the last 20 min. Mean PMLSS was 244+/
      45 W, according to 75% of VO2max. Mean of BLCMLSS was 5.3+/-1.5 mmol/l/min, mean
      of HRMLSS was 166+/-10 1/min. The coefficient of variability (CV) was calculated
      for PMLSS, BLCMLSS and HRMLSS with 3%, 16.6% and 6.3%, respectively. The Intra
      Class-Coefficient for PMLSS, BLCMLSS and for HRMLSS was determined with 0.98
      (p<=0.001), 0.71 (p<=0.001), 0.92 (p<=0.001) respectively. PMLSS and HRMLSS are
      characterized by a low day-to-day variability that is comparable with results of
      different lactate threshold concepts. In comparison to PMLSS, BLCMLSS shows a
      greater day-to-day-variability.

PMID- 22972243
TI  - Determination of the maximal lactate steady state in obese Zucker rats.
AB  - This study aims to identify the maximum lactate steady state (MLSS) in obese rats
      in order to provide a more effective tool in the exercise training prescription
      for this important animal model. To make such determination, obese (Zucker, n=5)
      (390.0+/-18.8 g) and lean (Wistar, n=5) (227.3+/-26.2 g) rats were studied. After
      adaptation of animals to treadmill, the MLSS was determined by using 3 different
      velocities (10 m.min-1, 12.5 m.min-1 and 15 m.min-1 for Zucker and 15 m.min-1, 20
      m.min-1 and 25 m.min-1 for Wistar). The MLSS was defined as the highest blood
      lactate concentration that increased up to 1 mmol.L-1 during constant exercise.
      In obese rats, the MLSS was found in a velocity considerably lower than in lean
      controls (12.5 m.min-1 and 20 m.min-1), respectively (p<0.05). Therefore, the
      identification of MLSS in obese Zucker rats is an important tool for exercise
      prescription and evaluation in obese rat models.

PMID- 22972244
TI  - Heart rate variability during 6-min walk test in adults aged 40 years and older.
AB  - We evaluated age- and sex-dependent differences in heart rate variability (HRV)
      during the 6-min walk test (6MWT) in healthy adults. We also evaluated the
      intensity of the 6MWT based on HRV. 78 participants aged 40-49, 50-59, 60-69, and
      >= 70 years (42 females; 36 men) performed the 6MWT. Heart rate and HRV were
      monitored 1 min at rest and during the last 2-min of the test. The root mean
      square (RMSSD), instantaneous beat-to-beat variability (SD1), and long-term
      standard deviation (SD2) of RR intervals were calculated. The SD1 <3 ms at the
      end of the 6MWT was defined as high-intensity exercise. Despite the significantly
      higher peak values of heart rate observed for women, we did not find sex- and age
      related differences in HRV during the 6MWT. The ROC curve identified percentage
      of maximum heart rate >67% as the best cut-point for prediction of high-intensity
      exercise with 94% of sensitivity and 65% of specificity (area under the
      curve=0.804). We may conclude that autonomic modulation of heart rate during
      exercise was not dependent of age and sex. The HRV assessment during walking
      enables a valid estimation of exercise intensity in adults. We may therefore
      suggest the use of 6MWT for assessing exercise capacity and for prescribing
      exercises in adults aged 40 yrs and older.

PMID- 22972246
TI  - Negative interaction between indomethacin and exercise in mice.
AB  - We examined the possible negative interaction of the combined use of the NSAID
      indomethacin (IND) and exercise in mice. Mice were assigned to one of 4 groups:
      Exercise 2.5 mg/kg IND (Ex-2.5), Sedentary 2.5 mg/kg IND (Sed-2.5), Exercise 5.0
      mg/kg IND (Ex-5.0) and Sedentary 5.0 mg/kg IND (Sed-5.0). Mice were given IND
      (gavage) 1 h prior to exercise (treadmill run at 30 m/min, 8% grade for 90 min)
      or rest for 14 consecutive days. Run times, body weight and mortality were
      recorded daily. Sed-5.0 was highly toxic and caused 70% mortality compared to Sed
      2.5, which was well tolerated (0% mortality) (P<0.05). While the addition of
      exercise had no greater effect on mortality in Ex-5.0, it increased it in the 2.5
      group (52% vs. 0%; P<0.05). Run time was reduced from baseline beginning on day 2
      (Ex-5.0), or day 3 (Ex-2.5) (P<0.05). Body weight (recorded in the 2.5 mg/kg
      groups only) was decreased from baseline in Ex-2.5 and Sed-2.5 (P<0.05), but this
      effect occurred earlier and was of greater magnitude in Ex-2.5. Exercise combined
      with IND use can lead to serious side effects in mice. Future research is needed
      to test the hypothesis that this effect is due to increased GI permeability and
      whether humans are also at risk.

PMID- 22972245
TI  - Training environment and Vitamin D status in athletes.
AB  - This study assessed the associations between gender, anthropometry, predominant
      training environment and Vitamin D status in 72 elite athletes. Additionally, any
      links between Vitamin D status and recent injury/health status, or sun protection
      practices were investigated. Athletes underwent an anthropometric assessment and
      provided venous blood samples for the determination of 25-hydroxyvitamin D
      (25(OH)D), the accepted biological marker of Vitamin D status. Finally, athletes
      completed a questionnaire relating to their recent training and injury history,
      and their sun protection practices. The athlete cohort were divided by
      predominant training environment as either indoor, outdoor, or mixed training
      environment athletes. The average ( +/- SD) 25(OH)D levels of the group were 111
      +/- 37 nmol/L, with the indoor training group (90 +/- 28 nmol/L) significantly
      lower than the outdoor (131 +/- 35 nmol/L), and mixed (133 +/- 29 nmol/L)
      training groups (p = 0.0001). Anthropometrical measures were positively
      associated with 25(OH)D levels; however, recent injury status or sun protection
      practice showed no association. Given the significant differences in 25(OH)D
      levels between the outdoor and indoor predominant training environments, coaches
      of indoor athletes may wish to monitor their athletes' Vitamin D levels
      throughout the year, in order to avoid any possibilities of a deficiency
      occurring.

PMID- 22972247
TI  - Seated double-poling ergometer performance of individuals with spinal cord injury
      - a new ergometer concept for standardized upper body exercise.
AB  - This study aimed to evaluate biomechanics during seated double-poling exercises
      in individuals with spinal cord injury (SCI) and to compare these with those of
      able-bodied persons (AB). 26 participants volunteered for the study; 13 with SCI
      (injury levels C7-T12), and 13 AB. A seated double-poling ergometer (SDPE) was
      developed. 3-dimensional kinematics was measured and piezoelectric force sensors
      were used to register force in both poles for calculation of power during
      incremental intensities. Significantly lower power outputs, (143.2 +/- 51.1 vs.
      198.3 +/- 74.9 W) and pole forces (137.1 +/- 43.1 vs. 238.2 +/- 81.2 N) were
      observed during maximal effort in SCI compared to AB. Sagittal upper trunk range
      of motion increased with intensity and ranged from 6.1-34.8 degrees  for SCI, and
      6.9-31.3 degrees  for AB, with larger peak amplitudes in flexion for AB (31.4 +/-
      12.9 degrees ) compared to SCI (10.0 +/- 8.0 degrees ). All subjects with SCI
      were able to exercise on the SDPE. Upper body kinematics, power and force outputs
      increased with intensity in both groups, but were in general, lower in SCI. In
      conclusion, the SDPE could be successfully used at low to high work intensities
      enabling both endurance and strength training for individuals with SCI.

PMID- 22972248
TI  - The use of heart rate variability in assessing precompetitive stress in high
      standard judo athletes.
AB  - The objective of this study is to examine the sensitivity to and changes in heart
      rate variability (HRV) in stressful situations before judo competitions and to
      observe the differences among judo athletes according to their competitive
      standards in both official and unofficial competitions. 24 (10 male and 14
      female) national- and international-standard athletes were evaluated. Each
      participant answered the Revised Competitive State Anxiety Inventory (CSAI-2R)
      and their HRV was recorded both during an official and unofficial competition.
      The MANOVA showed significant main effects of the athlete's standard and the type
      of competition in CSAI-2R, in HRV time domain, in HRV frequency domain and in HRV
      nonlinear analysis (p<0.05). International-standard judo athletes have lower
      somatic anxiety, cognitive anxiety, heart rate and low-high frequency ratio than
      national-standard athletes (p<0.05). International-standard athletes have a
      higher confidence, mean RR interval, standard deviation of RR, square root of the
      mean squared difference of successive RR intervals, number of consecutive RR that
      differ by more than 5 ms, short-term variability, long-term variability, long
      range scaling exponents and short-range scaling exponent than national-standard
      judo athletes. In conclusion, international-standard athletes show less pre
      competitive anxiety than the national-standard athletes and HRV analysis is
      sensitive to changes in pre-competitive anxiety.

PMID- 22972249
TI  - Reproducibility of pacing profiles in competitive swimmers.
AB  - This study aimed at determining the reproducibility of pacing profiles (PP)
      during simulated swimming trials as well as the comparison between simulated and
      real competitions (RC). Sixteen competitive front crawl swimmers (7 females, 9
      males) performed 2 * 200 m, 2 * 400 m and 2 * 800 m tests, each test 7 days
      apart. All 100 m split (ST) and total times (TT) were recorded (additionally 50 m
      ST for the 200 m bouts). The PP of one RC within a maximum of 8 weeks before or
      after data acquisition was used for comparison. No difference was observed
      between test and retest for TT (p<0.16). Coefficients of variation (CV) for all
      ST during 800 m were between 0.9 and 1.8% (standard error of measurement
      (SEM)=0.6-2.1 s), except for the last 2 sections (CV=2.5% and 2.9%). During 400 m
      and 200 m, CV was below 1.7% for each section (SEM=0.4-1.7 s). Mean differences
      between test and retest ranged from 1.8 s (Cl: 0.1-3.4 s) in the 400 m bouts to
      4.1 s (Cl: 1.3-9.5 s) for the 800 m races. Although section times were faster
      during all sections of RC compared to SC, PP was similar during both trials
      (p>0.22). However, swimmers were faster in each section during RC. In conclusion,
      PP seem stable, at least during the first three quarters of the race.
      Furthermore, simulated trials seem to be an acceptable model to analyse PP in
      competitive swimming.

PMID- 22972250
TI  - Effect of fat and CHO meals on intermittent exercise in soccer players.
AB  - Pre-exercise meals containing carbohydrates (CHO) are recommended to athletes,
      although there is evidence to suggest that a high fat meal prior to exercise
      increases utilisation of fats yet may not adversely affect performance. This
      study investigated the effect of a high fat and high CHO pre-exercise meal prior
      to high intensity intermittent exercise. Ten male recreational soccer players
      performed a soccer specific protocol followed by a 1 km time trial 3 1/2 h after
      ingesting one of 2 test meals, high fat meal (HFM) or a high CHO meal (HCM).
      Blood glucose, fatty acids (FA), glycerol, beta-hydroxybutyrate, lactate and
      insulin were assessed prior to the meal, pre-exercise, half-time, and post
      exercise, whilst rates of CHO and fat oxidation were determined at 4 time points
      during the exercise as well as heart rate (HR) and rating of perceived exertion
      (RPE). Significant increases in FA, glycerol, beta-hydroxybutyrate and fat
      oxidation after the HFM were observed, while CHO oxidation was significantly
      higher following the HCM (P<0.05). No performance effect was found for the 1 km
      time trial (HFM: 228.6+14.4 s; HCM: 229.4+26.5 s) (mean+SD). These findings
      suggest that the type of meal ingested prior to soccer simulated exercise has an
      impact on metabolism, but not on the subsequent performance as determined in the
      present study.

PMID- 22972251
TI  - The interaction between intra-cyclic variation of the velocity and mean swimming
      velocity in young competitive swimmers.
AB  - The aim of this study was to assess the relationship between the intra-cyclic
      variation of the horizontal velocity (dv) and the velocity of the 4 competitive
      swimming techniques in young swimmers. 45 young swimmers performed a set of
      maximal 4 * 25 m (freestyle, backstroke, breaststroke and butterfly stroke) swims
      with in water start. A speed-meter cable was attached to the swimmer's hip. The
      dv and the swimming velocity were analyzed. Within-subject tests presented
      significant variations in the dv based on the swimming technique. Post-hoc test
      revealed significant differences across all pair-wised swimming techniques
      (P<0.001), except for the comparison between freestyle and backstroke (P=0.98).
      The dv was higher in the breaststroke, followed by the butterfly, the backstroke
      and the freestyle. The quadratic models had the best goodness-of-fit and the
      lower error of estimation for the relationship between the dv and the swimming
      velocity in all swimming techniques (0.24 <= R(2) <= 0.51). As a conclusion,
      there is a non-linear relationship where the increase of swimming velocity leads
      to a decrease of dv in young competitive swimmers.

PMID- 22972252
TI  - Comparison between several muscle strength and cardiorespiratory fitness indices
      with body composition and energy expenditure in obese postmenopausal women.
AB  - The purpose of this study was to compare the relationship of several muscle
      strength and cardiorespiratory fitness indices with body composition and energy
      expenditure in obese postmenopausal women. This was a cross-sectional study
      involving 72 obese postmenopausal women (age: 60.0+/-4.8 years; body mass index:
      34.1+/-3.5 kg/m2). Muscle strength was determined by hand dynamometer and
      cardiorespiratory fitness was measured by indirect calorimetry. Muscle strength
      and cardiorespiratory fitness were expressed in absolute (kg and L/min,
      respectively) and in relative values (kg/body weight (BW) and kg/lean body mass
      (LBM) for muscle strength and ml/min/kg BW and ml/min kg LBM for
      cardiorespiratory fitness). Body composition was measured using dual energy x-ray
      absorptiometry. Anthropometric (waist and thigh circumference), physical activity
      energy expenditure and daily number of steps (SenseWear armband) as well as blood
      pressure were also assessed. Correlations of muscle strength and
      cardiorespiratory fitness indices with body composition and energy expenditure
      showed several similarities, however, several variations were also observed.
      Furthermore, our results showed that age and waist circumference were the primary
      independent predictors for the muscle strength indices, explaining 22-37% of the
      variance and % body fat and age were the primary predictors for the
      cardiorespiratory fitness indices, explaining 18-40% of the variance. In
      conclusion, the present study indicates that the different methods of expressing
      muscle strength and cardiorespiratory fitness may display several variations and
      similarities with body composition and energy expenditure associations.
      Therefore, interpretations of relationships between muscle strength and
      cardiorespiratory indices with body composition and energy expenditure factors
      should take in account the method used to express them.

PMID- 22972253
TI  - Abstracts of the Irish Endocrine Society 37th Annual Meeting. November 9-10,
      2012. Dublin, Ireland.

PMID- 22972254
TI  - Engineered nonviral nanocarriers for intracellular gene delivery applications.
AB  - The efficient delivery of nucleic acids into mammalian cells is a central aspect
      of cell biology and of medical applications, including cancer therapy and tissue
      engineering. Non-viral chemical methods have been received with great interest
      for transfecting cells. However, further development of nanocarriers that are
      biocompatible, efficient and suitable for clinical applications is still
      required. In this paper, the different material platforms for gene delivery are
      comparatively addressed, and the mechanisms of interaction with biological
      systems are discussed carefully.

PMID- 22972255
TI  - Count on me.

PMID- 22972256
TI  - Secret weapons.

PMID- 22972257
TI  - The name game.

PMID- 22972258
TI  - Predatory publishers are corrupting open access.

PMID- 22972270
TI  - Ice loss shifts Arctic cycles.

PMID- 22972271
TI  - Europe on alert for flying invaders.

PMID- 22972272
TI  - EU battles over research billions.

PMID- 22972273
TI  - Misconduct ruling is silent on intent.

PMID- 22972274
TI  - Cameras to focus on dark energy.

PMID- 22972275
TI  - India moves to tackle antibiotic resistance.

PMID- 22972276
TI  - Deep-sea research: Dive master.

PMID- 22972277
TI  - Microwave weapons: Wasted energy.

PMID- 22972278
TI  - Future impact: Predicting scientific success.

PMID- 22972279
TI  - Science policy: Well-funded investigators should receive extra scrutiny.

PMID- 22972285
TI  - Genomics: ENCODE leads the way on big data.

PMID- 22972286
TI  - History of science: Wallace pioneered astrobiology too.

PMID- 22972287
TI  - Media: Animal variants in sexual behaviour.

PMID- 22972288
TI  - Research practice: A code of conduct for European scientists.

PMID- 22972289
TI  - Policy: Clarify the limits of climate models.

PMID- 22972290
TI  - Biogeochemistry: Drought and tropical soil emissions.

PMID- 22972291
TI  - Social science: Poked to vote.

PMID- 22972292
TI  - Organic synthesis: A biochemical messenger made easily.

PMID- 22972293
TI  - Cell biology: Dormant and restless skin stem cells.

PMID- 22972294
TI  - Gut microbes and health.

PMID- 22972295
TI  - Diversity, stability and resilience of the human gut microbiota.
AB  - Trillions of microbes inhabit the human intestine, forming a complex ecological
      community that influences normal physiology and susceptibility to disease through
      its collective metabolic activities and host interactions. Understanding the
      factors that underlie changes in the composition and function of the gut
      microbiota will aid in the design of therapies that target it. This goal is
      formidable. The gut microbiota is immensely diverse, varies between individuals
      and can fluctuate over time - especially during disease and early development.
      Viewing the microbiota from an ecological perspective could provide insight into
      how to promote health by targeting this microbial community in clinical
      treatments.

PMID- 22972296
TI  - Reciprocal interactions of the intestinal microbiota and immune system.
AB  - The emergence of the adaptive immune system in vertebrates set the stage for
      evolution of an advanced symbiotic relationship with the intestinal microbiota.
      The defining features of specificity and memory that characterize adaptive
      immunity have afforded vertebrates the mechanisms for efficiently tailoring
      immune responses to diverse types of microbes, whether to promote mutualism or
      host defence. These same attributes can put the host at risk of immune-mediated
      diseases that are increasingly linked to the intestinal microbiota. Understanding
      how the adaptive immune system copes with the remarkable number and diversity of
      microbes that colonize the digestive tract, and how the system integrates with
      more primitive innate immune mechanisms to maintain immune homeostasis, holds
      considerable promise for new approaches to modulate immune networks to treat and
      prevent disease.

PMID- 22972297
TI  - Functional interactions between the gut microbiota and host metabolism.
AB  - The link between the microbes in the human gut and the development of obesity,
      cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is
      becoming clearer. However, because of the complexity of the microbial community,
      the functional connections are less well understood. Studies in both mice and
      humans are helping to show what effect the gut microbiota has on host metabolism
      by improving energy yield from food and modulating dietary or the host-derived
      compounds that alter host metabolic pathways. Through increased knowledge of the
      mechanisms involved in the interactions between the microbiota and its host, we
      will be in a better position to develop treatments for metabolic disease.

PMID- 22972298
TI  - Genomic approaches to studying the human microbiota.
AB  - The human body is colonized by a vast array of microbes, which form communities
      of bacteria, viruses and microbial eukaryotes that are specific to each
      anatomical environment. Every community must be studied as a whole because many
      organisms have never been cultured independently, and this poses formidable
      challenges. The advent of next-generation DNA sequencing has allowed more
      sophisticated analysis and sampling of these complex systems by culture
      independent methods. These methods are revealing differences in community
      structure between anatomical sites, between individuals, and between healthy and
      diseased states, and are transforming our view of human biology.

PMID- 22972299
TI  - Stabilization of Leidenfrost vapour layer by textured superhydrophobic surfaces.
AB  - In 1756, Leidenfrost observed that water drops skittered on a sufficiently hot
      skillet, owing to levitation by an evaporative vapour film. Such films are stable
      only when the hot surface is above a critical temperature, and are a central
      phenomenon in boiling. In this so-called Leidenfrost regime, the low thermal
      conductivity of the vapour layer inhibits heat transfer between the hot surface
      and the liquid. When the temperature of the cooling surface drops below the
      critical temperature, the vapour film collapses and the system enters a nucleate
      boiling regime, which can result in vapour explosions that are particularly
      detrimental in certain contexts, such as in nuclear power plants. The presence of
      these vapour films can also reduce liquid-solid drag. Here we show how vapour
      film collapse can be completely suppressed at textured superhydrophobic surfaces.
      At a smooth hydrophobic surface, the vapour film still collapses on cooling,
      albeit at a reduced critical temperature, and the system switches explosively to
      nucleate boiling. In contrast, at textured, superhydrophobic surfaces, the vapour
      layer gradually relaxes until the surface is completely cooled, without
      exhibiting a nucleate-boiling phase. This result demonstrates that topological
      texture on superhydrophobic materials is critical in stabilizing the vapour layer
      and thus in controlling--by heat transfer--the liquid-gas phase transition at hot
      surfaces. This concept can potentially be applied to control other phase
      transitions, such as ice or frost formation, and to the design of low-drag
      surfaces at which the vapour phase is stabilized in the grooves of textures
      without heating.

PMID- 22972300
TI  - A 61-million-person experiment in social influence and political mobilization.
AB  - Human behaviour is thought to spread through face-to-face social networks, but it
      is difficult to identify social influence effects in observational studies, and
      it is unknown whether online social networks operate in the same way. Here we
      report results from a randomized controlled trial of political mobilization
      messages delivered to 61 million Facebook users during the 2010 US congressional
      elections. The results show that the messages directly influenced political self
      expression, information seeking and real-world voting behaviour of millions of
      people. Furthermore, the messages not only influenced the users who received them
      but also the users' friends, and friends of friends. The effect of social
      transmission on real-world voting was greater than the direct effect of the
      messages themselves, and nearly all the transmission occurred between 'close
      friends' who were more likely to have a face-to-face relationship. These results
      suggest that strong ties are instrumental for spreading both online and real
      world behaviour in human social networks.

PMID- 22972303
TI  - Nanoporous Ge electrode as a template for nano-sized ( <5 nm) Au aggregates.
AB  - In this paper we present the extremely peculiar electrical properties of
      nanoporous Ge. A full and accurate electrical characterization showed an
      unexpected and extremely high concentration of positive carriers. Electrochemical
      analyses showed that nanoporous Ge has improved charge transfer properties with
      respect to bulk Ge. The electrode behavior, together with the large surface-to
      volume ratio, make nanoporous Ge an efficient nanostructured template for the
      realization of other porous materials by electrodeposition. The pores were
      efficiently decorated by Au nanoparticles of diameter as low as 1-5 nm, prepared
      by electrochemical deposition. These new results demonstrate the potential and
      efficient use of nanoporous Ge as a nanostructured template for nano-sized Au
      aggregates, opening the way for the realization of innovative sensor devices.

PMID- 22972301
TI  - Increased proteasome activity in human embryonic stem cells is regulated by
      PSMD11.
AB  - Embryonic stem cells can replicate continuously in the absence of senescence and,
      therefore, are immortal in culture. Although genome stability is essential for
      the survival of stem cells, proteome stability may have an equally important role
      in stem-cell identity and function. Furthermore, with the asymmetric divisions
      invoked by stem cells, the passage of damaged proteins to daughter cells could
      potentially destroy the resulting lineage of cells. Therefore, a firm
      understanding of how stem cells maintain their proteome is of central importance.
      Here we show that human embryonic stem cells (hESCs) exhibit high proteasome
      activity that is correlated with increased levels of the 19S proteasome subunit
      PSMD11 (known as RPN-6 in Caenorhabditis elegans) and a corresponding increased
      assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to
      increase proteasome assembly and activity. FOXO4, an insulin/insulin-like growth
      factor-I (IGF-I) responsive transcription factor associated with long lifespan in
      invertebrates, regulates proteasome activity by modulating the expression of
      PSMD11 in hESCs. Proteasome inhibition in hESCs affects the expression of
      pluripotency markers and the levels of specific markers of the distinct germ
      layers. Our results suggest a new regulation of proteostasis in hESCs that links
      longevity and stress resistance in invertebrates to hESC function and identity.

PMID- 22972304
TI  - Reduction of nitric oxide-mediated gamma-amino butyric acid release in rostral
      ventrolateral medulla is involved in superoxide-induced sympathoexcitation of
      hypertensive rats.
AB  - BACKGROUND: The rostral ventrolateral medulla (RVLM) in the brainstem is
      responsible for regulation of the sympathetic nervous system. In the RVLM, nitric
      oxide (NO)-mediated gamma-amino butyric acid (GABA) is a major sympathoinhibitory
      amino acid neurotransmitter and superoxide is a major sympathoexcitatory factor.
      In this study, we investigated whether or not NO-mediated GABA release is
      involved in superoxide-induced sympathoexcitation in the RVLM of hypertensive
      rats. METHODS AND RESULTS: For our model hypertensive rats with
      sympathoexcitation, we used stroke-prone spontaneously hypertensive rats (SHRSP).
      GABA levels in the RVLM were measured by in vivo microdialysis. Microinjection of
      tempol, a superoxide scavenger, into the RVLM decreased arterial pressure (AP),
      heart rate (HR), and renal sympathetic nerve activity (RSNA) with an increase in
      GABA release in the RVLM. Microinjection of N(G)-monomethyl-L-arginine (L-NMMA),
      an NO synthase inhibitor, into the RVLM increased AP, HR, and RSNA with a
      decrease in GABA release in the RVLM. Prior microinjection of L-NMMA into the
      RVLM attenuated the tempol-induced changes in AP, HR, RSNA, and GABA release in
      the RVLM. Microinjection of bicuculline, a GABA receptor blocker, into the RVLM
      attenuated the tempol- and L-NMMA-induced changes in AP, HR, and RSNA.
      CONCLUSIONS: The findings suggest that reduction of NO-mediated GABA release in
      the RVLM is partly involved in superoxide-induced sympathoexcitation of SHRSP.

PMID- 22972305
TI  - Cellular prion protein accelerates colorectal cancer metastasis via the Fyn-SP1
      SATB1 axis.
AB  - The cellular prion protein (PrPc) is a glycoprotein anchored by
      glycosylphosphatidylinositol to the cell surface and is abundantly expressed in
      various tissues. The putative roles of PrPc are thought to be related to cell
      signaling, survival, and differentiation and cancer progression. In this study,
      we demonstrated that the expression of PrPc correlates with a more aggressive and
      histologically unfavorable disease in colorectal carcinomas. Moreover, we found
      that PrPc mediates the process of epithelial-mesenchymal transition and, thereby,
      promotes CRC metastasis. Transcriptome profiling of PrPc-depleted cells revealed
      downregulation of the special AT-rich sequence-binding protein-1 (SATB1). PrPc is
      demonstrated to be involved in regulating SATB1 expression via the Fyn-SP1
      pathway. Since SATB1 has been previously proposed as a key protein that controls
      tumor development and progression, knockdown of PrPc resulted in a reduced
      metastatic capacity in CRC cells, as well as a reduction in distant metastases in
      vivo. In conclusion, our data characterize a novel molecular mechanism that links
      PrPc expression to the regulation of CRC metastasis. Targeting PrPc will,
      therefore, be a promising strategy to overcome the metastatic advantage in
      colorectal tumors.

PMID- 22972306
TI  - Isolation of lymphocytes from mouse genital tract mucosa.
AB  - Mucosal surfaces, including in the gastrointestinal, urogenital, and respiratory
      tracts, provide portals of entry for pathogens, such as viruses and bacteria.
      Mucosae are also inductive sites in the host to generate immunity against
      pathogens, such as the Peyers patches in the intestinal tract and the nasal
      associated lymphoreticular tissue in the respiratory tract. This unique feature
      brings mucosal immunity as a crucial player of the host defense system. Many
      studies have been focused on gastrointestinal and respiratory mucosal sites.
      However, there has been little investigation of reproductive mucosal sites. The
      genital tract mucosa is the primary infection site for sexually transmitted
      diseases (STD), including bacterial and viral infections. STDs are one of the
      most critical health challenges facing the world today. Centers for Disease
      Control and Prevention estimates that there are 19 million new infectious every
      year in the United States. STDs cost the U.S. health care system $17 billion
      every year, and cost individuals even more in immediate and life-long health
      consequences. In order to confront this challenge, a greater understanding of
      reproductive mucosal immunity is needed and isolating lymphocytes is an essential
      component of these studies. Here, we present a method to reproducibly isolate
      lymphocytes from murine female genital tracts for immunological studies that can
      be modified for adaption to other species. The method described below is based on
      one mouse.

PMID- 22972308
TI  - Minocycline and fluorocitrate suppress spinal nociceptive signaling in
      intrathecal IL-1beta-induced thermal hyperalgesic rats.
AB  - We previously demonstrated that intrathecal IL-1beta caused thermal hyperalgesia
      in rats. This study was conducted to examine the effects and cellular mechanisms
      of glial inhibitors on IL-1beta-induced nociception in rats. The effects of
      minocycline (20 MUg), fluorocitrate (1 nmol), and SB203580 (5 MUg) on IL-1beta
      (100 ng) treatment in rats were measured by nociceptive behaviors, western
      blotting of p38 mitogen-activated protein kinase (MAPK) and inducible nitric
      oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels,
      and immunohistochemical analyses. The results demonstrated that intrathecal IL
      1beta activated microglia and astrocytes, but not neurons, in the dorsal horn of
      the lumbar spinal cord, as evidenced by morphological changes and increased
      immunoreactivity, phosphorylated p38 (P-p38) MAPK, and iNOS expression; the
      activation of microglia and astrocytes peaked at 30 min and lasted for 6 h. The
      immunoreactivities of microglia and astrocytes were significantly increased at 30
      min (6.6- and 2.7-fold, respectively) and 6 h (3.3- and 4.0-fold, respectively)
      following IL-1beta injection, as compared with saline controls at 30 min (all P <
      0.01). IL-1beta induced P-p38 MAPK and iNOS expression predominantly in microglia
      and less in astrocytes. Minocycline, fluorocitrate, or SB203580 pretreatment
      suppressed this IL-1beta-upregulated P-p38 MAPK mainly in microglia and iNOS
      mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline
      and fluorocitrate pretreatment abrogated IL-1beta-induced NO release and thermal
      hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580
      effectively suppressed the IL-1beta-induced central sensitization and
      hyperalgesia in rats.

PMID- 22972309
TI  - NIR fluorescent biotinylated cyanine dye: optical properties and combination with
      quantum dots as a potential sensing device.
AB  - We present a water soluble and fluorescent biotinylated probe derived from a
      carbocyanine dye. A high efficiency of energy transfer was measured when the dyes
      were placed on the surface of streptavidin conjugated quantum dots. The system is
      a model platform for potential application as a FRET-based fluorescent sensor.

PMID- 22972310
TI  - Effect of tacrolimus on myocardial infarction is associated with inflammation,
      ROS, MAP kinase and Akt pathways in mini-pigs.
AB  - AIM: This study tested the hypothesis that tacrolimus therapy limited left
      ventricular (LV) infarct and remodeling by suppressing the inflammatory response,
      oxidative stress and regulating the mitogen-activated protein kinase (MAPK) and
      Akt signaling pathways in an acute myocardial infarction (AMI) mini-pig model by
      ligating the left anterior descending coronary artery (LAD). METHODS: Twelve male
      mini-pigs were equally randomized into AMI treated by saline (3.0 mL) (AMI(S)),
      and AMI treated by tacrolimus (0.5 mg) (AMI(T)). Thirty minutes after the
      procedure, intra-LAD injections were performed just beyond the ligation. RESULTS:
      Inflammatory biomarkers at transcription or protein levels [matrix
      metalloproteinase (MMP9), plasminogen activator inhitor-1, tumor necrotic factor
      (TNF-alpha), nuclear factor (NF)-kappaB] and the cellular level (CD40+ cells)
      were markedly higher in AMI(S) than in AMI(T) animals (all p<0.001). Fibrosis
      biomarkers at the protein level (alpha-smooth muscle actin, transforming growth
      factor-beta) and Sirius-red staining were notably higher in AMI(S) than in AMI(T)
      animals (all p<0.03). Antioxidant biomarkers at protein or transcription levels
      (heme oxygenase-1, quinone oxidoreductase-1, glutathione reductase, glutathione
      peroxidase) were significantly higher in AMI(S) than in AMI(T) animals (all
      p<0.01). Protein expressions of ERK1, p38 MAPK and Akt were markedly increased in
      AMI(S) compared to AMI(T) animals (all p<0.001). Significantly aggravated LV
      infarction and remodeling were noted in AMI(S) compared to AMI(T) animals,
      whereas LV ejection fraction was markedly decreased in AMI(S) compared to AMI(T)
      animals (all p<0.001). CONCLUSIONS: Intra-coronary administration of tacrolimus
      attenuated inflammation and MAPK signaling, limited infarct size, and preserved
      LV function.

PMID- 22972311
TI  - Age- and gender-associated determinants of carotid intima-media thickness: a
      community-based study.
AB  - AIM: Few population-based studies have assessed the risk factors of and gender
      differences in intima-media thickness (IMT) at the common carotid artery (CCA)
      for different age groups. OBJECTIVE: Factors determining age and gender
      differences in IMT were studied in ethnic Chinese participants of the Chin-Shan
      Community Cardiovascular Cohort in Taiwan. METHODS: From July 1994 through August
      1996, the CCA-IMT of 1203 men and 1487 women aged 35 years or more was measured
      using high-resolution B-mode carotid ultrasound. Cardiovascular risk factors were
      recorded for each subject. RESULTS: The CCA-IMT consistently increased with age
      and was more in men than in women. For participants aged 55 years or more, women
      showed a more rapid increase in systolic blood pressure (SBP) and low-density
      lipoprotein cholesterol (LDL) than men. The gender difference in CCA-IMT became
      insignificant after 75 years of age. The major determinants of CCA-IMT in
      addition to age and gender were body mass index at 35-44 years of age, LDL in
      both genders and SBP in women at 45-54 years old, SBP at 55-64 and 65-74 years
      old, and women with left ventricular hypertrophy, hypertension with medication,
      and high LDL levels at 65-74 years old after multivariate linear regression
      analysis. For those aged over 75 years, SBP was an important determinant of CCA
      IMT. CONCLUSIONS: The CCA-IMT increases with age and its determinants are
      associated with age and gender. The rapid increase in cardiovascular risk factors
      in women after 55 years of age attenuates the female advantage in CCA-IMT.

PMID- 22972313
TI  - Successful fixation of Mason type 2 radial head fractures using Meniscus Arrows.
AB  - PURPOSE: Previous experience has revealed excellent outcomes when using the
      Meniscus Arrow (Conmed Linvatec Ltd., Tampere, Finland) bioabsorable meniscal
      repair system for the fixation of small fracture fragments. This study describes
      the results of the fixation of Mason type 2 radial head fractures with these
      Arrows in a prospective series of 21 patients. METHODS: Between 2006 and 2010, a
      total of 21 patients were treated with Meniscus Arrows for the fixation of Mason
      type 2 fractures of the radial head during an open procedure. Twenty-one, twenty
      and seventeen patients were followed up at 2 and 6 post-operative weeks, 18 weeks
      and 24 months, respectively. Radiographs were obtained during follow-up visits,
      and range of motion was classified according to the Weseley classification.
      RESULTS: At 24 post-operative months, 88 % of patients showed 'excellent' and 12
      % showed 'good' results in terms of extension. All patients (100 %) showed
      'excellent' results for flexion, supination and pronation. Uneventful healing of
      the fracture was observed in all patients. No complications were noted.
      CONCLUSION: This study shows promising outcomes for the use of Meniscus Arrows as
      fixation devices in the treatment for Mason type 2 fractures of the radial head.

PMID- 22972312
TI  - Origin of developmental precursors dictates the pathophysiologic role of cardiac
      fibroblasts.
AB  - Fibroblasts in the heart play a critical function in the secretion and modulation
      of extracellular matrix critical for optimal cellular architecture and mechanical
      stability required for its mechanical function. Fibroblasts are also intimately
      involved in both adaptive and nonadaptive responses to cardiac injury.
      Fibroblasts provide the elaboration of extracellular matrix and, as
      myofibroblasts, are responsible for cross-linking this matrix to form a
      mechanically stable scar after myocardial infarction. By contrast, during heart
      failure, fibroblasts secrete extracellular matrix, which manifests itself as
      excessive interstitial fibrosis that may mechanically limit cardiac function and
      distort cardiac architecture (adverse remodeling). This review examines the
      hypothesis that fibroblasts mediating scar formation and fibroblasts mediating
      interstitial fibrosis arise from different cellular precursors and in response to
      different autocoidal signaling cascades. We demonstrate that fibroblasts which
      generate scars arise from endogenous mesenchymal stem cells, whereas those
      mediating adverse remodeling are of myeloid origin and represent
      immunoinflammatory dysregulation.

PMID- 22972314
TI  - Returning to sports after surgical repair of acute proximal hamstring ruptures.
AB  - PURPOSE: Although the treatment of choice for acute proximal hamstring ruptures
      is now surgical repair, this technique is relatively new and requires further
      evaluation. Our hypothesis was that patients return to sports at the same level
      after surgical repair as before injury. METHODS: From 2002 to 2011, a prospective
      observational study including 34 patients, mean age 39.3 +/- 11.4 years old
      underwent surgical repair of an acute proximal hamstring rupture. Surgical,
      rehabilitation and follow-up protocols were standardized. Mean follow-up was 27.2
      +/- 22.9 months and there were no lost to follow-up. The primary outcome was the
      level of activity on the UCLA and Tegner scores. RESULTS: The mean UCLA score was
      9.1 +/- 1.3 before injury and 8.7 +/- 1.7 at the final follow-up (p = 0.03). The
      median Tegner activity level was 6 (range, 4-10) before injury and 6 (range, 3
      10) at the final follow-up (p = 0.05). The two scores were correlated (r = 0.76,
      p = 0.00001). Patients returned to sports within a mean 5.7 +/- 1.6 months, at
      the same level in 27 patients (79.4 %) and at a lower level in 7 patients (20.6
      %). The average hamstring/quadriceps ratio at 240 degrees /second was 54.7 +/-
      8.6 % which was positively correlated to the level of activity on the UCLA score
      (r = 0.49, n.s.). The level of satisfaction was related to their level of
      activity at the final follow-up (p = 0.03). CONCLUSION: Although surgical repair
      of acute proximal hamstring ruptures has significantly improved the functional
      prognosis of patients it remains a serious condition that can compromise future
      sports activities. LEVEL OF EVIDENCE: Case-control study, Level III.

PMID- 22972315
TI  - Atmospheric influences on water quality: a simulation of nutrient loading for the
      Pearl River Basin, USA.
AB  - Knowledge of water quality conditions is essential in assessing the health of
      riverine ecosystems. The goal of this study is to determine the degree to which
      water quality variables are related to precipitation and air temperature
      conditions for a segment of the Pearl River Basin near Bogalusa, LA, USA. The
      AQUATOX ecological fate simulation model is used to estimate daily total
      nitrogen, total phosphorus, and dissolved oxygen concentrations over a 2-year
      period. Daily modeled output for each variable was calibrated against reliably
      measured data to assess the accuracy. Observed data were plotted against
      simulated data for controlled and perturbed models for validation, and stepwise
      multiple regression analysis was used to quantify the relationships between the
      water quality and meteorological variables. Results suggest that daily dissolved
      oxygen is significantly negatively correlated to concurrent daily mean air
      temperature with a total explained variance of 0.679 (p < 0.01), and monthly
      dissolved oxygen is significantly negatively correlated to monthly mean air
      temperature with a total explained variance of 0.567 (p < 0.01). Total mean
      monthly phosphorus concentration is significantly positively related to the
      previous month's precipitation with a total explained variance of 0.302 (p <
      0.01). These relationships suggest that atmospheric conditions have a strong
      influence on water quality in the Pearl Basin. Therefore, environmental planners
      should expect that future climatic changes are likely to alter water quality.

PMID- 22972316
TI  - Drought impact assessment from monitoring the seasonality of vegetation condition
      using long-term time-series satellite images: a case study of Mt. Kenya region.
AB  - Drought-induced anomalies in vegetation condition over wide areas can be observed
      by using time-series satellite remote sensing data. Previous methods to assess
      the anomalies may include limitations in considering (1) the seasonality in terms
      of each vegetation-cover type, (2) cumulative damage during the drought event,
      and (3) the application to various types of land cover. This study proposed an
      improved methodology to assess drought impact from the annual vegetation
      responses, and discussed the result in terms of diverse landscape mosaics in the
      Mt. Kenya region (0.4 degrees  N 35.8 degrees  E ~ 1.6 degrees  S 38.4 degrees 
      E). From the 30-year annual rainfall records at the six meteorological stations
      in the study area, we identified 2000 as the drought year and 2001, 2004, and
      2007 as the normal precipitation years. The time-series profiles of vegetation
      condition in the drought and normal precipitation years were obtained from the
      values of Enhanced Vegetation Index (EVI; Huete et al. 2002), which were acquired
      from Terra MODIS remote sensing dataset (MOD13Q1) taken every 16 days at the
      scale of 250-m spatial resolution. The drought impact was determined by
      integrating the annual differences in EVI profiles between drought and normal
      conditions, per pixel based on nearly same day of year. As a result, we
      successfully described the distribution of landscape vulnerability to drought,
      considering the seasonality of each vegetation-cover type at every MODIS pixel.
      This result will contribute to the large-scale landscape management of Mt. Kenya
      region. Future study should improve this method by considering land-use change
      occurred during the long-term monitoring period.

PMID- 22972317
TI  - Contamination and ecological risk assessment of toxic trace elements in the Xi
      River, an urban river of Shenyang city, China.
AB  - The objectives of this study were to assess the enrichment, contamination, and
      ecological risk posed by toxic trace elements in the sediments of the Xi River in
      the industrialized city of Shenyang, China. Surface sediment and sediment core
      were collected; analyzed for toxic trace elements; and assessed with an index of
      geoaccumulation (Igeo), enrichment factor (EF) value, potential ecological risk
      factor (Er), ecological risk index (RI), and probable effect concentration
      quotient (PECQ). Elemental concentrations (milligram per kilogram) were 8.5-637.9
      for As, 6.5-103.9 for Cd, 12.2-21.9 for Co, 90.6-516.0 for Cr, 258.1-1,791.5 for
      Cu, 2.6-19.0 for Hg, 70.5-174.5 for Ni, 126.9-1,405.8 for Pb, 3.7-260.0 for Sb,
      38.4-100.4 for V, and 503-4,929 for Zn. The Igeo, EF, Er, and PECQ indices showed
      that the contamination of Cd and Hg was more serious than that of As, Cr, Cu, Ni,
      Pb, Sb, and Zn, whereas the presence of Co and V might be primarily from natural
      sources. The Igeo index for Cr and Ni might underestimate the degree of
      contamination, potentially as a result of high concentrations of these elements
      in the shale. The RI index was higher than 600, indicating a notably high
      ecological risk of sediment for the river. The average PECQ for As, Cd, Cr, Cu,
      Hg, Ni, Pb, and Zn ranged from 1.4 to 4.1 for surface sediment and from 5.2 to
      9.6 in the sediment cores, indicating a high potential for an adverse biological
      effect. It was concluded that the sediment in the Xi River was severely
      contaminated and should be remediated as a hazardous material.

PMID- 22972318
TI  - Oxidative DNA damage and in vivo mutagenicity caused by reactive oxygen species
      generated in the livers of p53-proficient or -deficient gpt delta mice treated
      with non-genotoxic hepatocarcinogens.
AB  - Oxidative stress is thought to participate in chemical carcinogenesis and may
      trigger gene mutations. To accurately assess the carcinogenesis risk posed to
      humans by chemical exposure, it is important to understand the pathways by which
      reactive oxygen species (ROS) are generated and the effects of the resulting
      oxidative stress. In the present study, p53-proficient and -deficient gpt delta
      mice were given pentachlorophenol (PCP), phenobarbital (PhB) or piperonyl
      butoxide (PBO), which are classified as non-genotoxic hepatocarcinogens in
      rodents, at the respective carcinogenic doses for 13 weeks. Exposure to PCP or
      PBO, but not PhB, invoked significant increases in liver DNA 8
      hydroxydeoxyguanosine (8-OHdG) levels. Treatment with PCP significantly increased
      mRNA levels of the gene encoding NAD(P):quinone oxidoreductase 1 (NQO1) in the
      liver, suggesting that redox cycling of the PCP metabolite
      tetrachlorohydroquinone gave rise to ROS. Exposure to PhB or PBO significantly
      elevated CYP 2B10 mRNA levels while NQO1 levels were also significantly increased
      in PBO-treated mice. Therefore, in addition to involvement of the CYP catalytic
      pathway in the ROS-generated system of PBO, catechol derivatives produced from
      the opening of the PBO functional group methylenedioxy ring probably resulted in
      ROS generation. However, PCP, PBO and PhB failed to increase gpt and red/gam gene
      mutations in the liver independently of p53. Overall, the action of oxidative
      stress by ROS derived from the metabolism of these carcinogens might be limited
      to cancer-promoting activity, which supports the previous classification of these
      carcinogens as non-genotoxic.

PMID- 22972319
TI  - Anthraquinone derivatives produced by marine-derived fungus Aspergillus
      versicolor EN-7.
AB  - The new anthraquinone derivative, 6,8-di-O-methylaverantin (1), together with six
      known congeners (2-7), were characterized from a culture extract of the marine
      algous fungus, Aspergillus versicolor EN-7. Their structures were elucidated by
      spectroscopic methods. A bioassay showed compounds 1, 2 and 5 to have weak
      inhibition against Escherichia coli, while compound 5 also displayed weak
      inhibition against Staphylococcus aureus.

PMID- 22972320
TI  - Accumulation of ACE inhibitory tripeptides, Val-Pro-Pro and Ile-Pro-Pro, in
      vascular endothelial cells.
AB  - The antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro, were successfully
      detected in the aorta of spontaneously hypertensive rats after orally
      administering these peptides by a guanidine-thiocyanate treatment to prevent
      proteolysis. Cy3-labeled versions of both peptides were localized in the
      endothelial cells of arterial vessels in the rats. The accumulation of both
      peptides in the endothelial cells suggested in vivo inhibitory activity of the
      angiotensin I-converting enzyme.

PMID- 22972321
TI  - Antifibrotic activity of diarylheptanoids from Betula platyphylla toward HSC-T6
      cells.
AB  - A chemical investigation of the n-butanol fraction of the inner bark of Betula
      platyphylla led to the isolation of seven diarylhepanoids, (-)-centrolobol (1),
      aceroside VII (2), aceroside VIII (3), (3R)-1,7-bis-(4-hydroxyphenyl)-3-heptanol
      3-O-[2,6-bis-O-(beta-D-apiofuranosyl)-beta-D-glucopyranoside (4), 1,7-bis-(4
      hydroxyphenyl)-5-hepten-3-one (5), platyphyllone (6) and platyphylloside (7). The
      antifibrotic effects of these isolates were evaluated with HSC-T6 cells by
      assessing cell proliferation. Among them, compounds 1, 2, 5 and 6 significantly
      inhibited the proliferation of HSCs in a dose-dependent manner at concentrations
      from 10 uM to 100 uM. Compound 5 in particular dramatically decreased the
      collagen content and increased the Caspase-3/7 activity. Taken together, the
      antifibrotic activity of B. platyphylla and its constituents might suggest
      therapeutic potential against liver fibrosis.

PMID- 22972322
TI  - Impairment of pachytene spermatogenesis in Dmrt7 deficient mice, possibly causing
      meiotic arrest.
AB  - Although Dmrt7 has been reported to be essential for male spermatogenesis, the
      molecular mechanism underlying pachytene spermatogenesis by Dmrt7 is not known.
      In the present study, by detailed analysis of Dmrt7 protein distribution in
      spermatocytes in the first wave of spermatogenesis, we clarified the profile of
      Dmrt7 expression and localization in pachytene spermatogenesis. Dmrt7-deficient
      spermatocytes were arrested in the pachytene stage, followed by apoptosis. We
      analyzed to determine whether every event in the spermatogenesis at the Dmrt7
      deficient mice progressed normally, because in several gene knockout mice with
      spermatogenic arrest described in the previous reports impairments of these
      events often appeared. Mutant mice showed normal synapsis and XY body formation,
      while impairment of meiotic sex chromosome inactivation (MSCI), decreased
      expression of backup genes, and increased expression of retrotransposons
      indicated incomplete meiotic recombination.

PMID- 22972323
TI  - Anti-influenza virus effects of elderberry juice and its fractions.
AB  - Elderberry (Sambucus nigra L.) has traditionally been used for treating influenza
      and colds. We evaluated the antiviral effect of concentrated juice of elderberry
      (CJ-E) on the human influenza A virus (IFV). CJ-E had a relatively strong effect
      on IFV-infected mice, although its anti-IFV activity was weak in a cell culture
      system. The in vivo anti-IFV activities of the fractions were determined after
      separating CJ-E by ultrafiltration and anion-exchange chromatography. Oral
      administration of the high-molecular-weight fractions of CJ-E to IFV-infected
      mice suppressed viral replication in the bronchoalveolar lavage fluids (BALFs),
      and increased the level of the IFV-specific neutralizing antibody in the serum,
      as well as the level of secretory IgA in BALFs and feces. Fr. II from high
      molecular-weight fraction HM, which contained acidic polysaccharides, showed
      relatively strong defense against IFV infection. We conclude that CJ-E had a
      beneficial effect by the stimulating immune response and preventing viral
      infection.

PMID- 22972324
TI  - Loss-of-function mutation in bi-functional marine bacterial sialyltransferase.
AB  - An alpha2,3-sialyltransferase produced by Photobacterium phosphoreum JT-ISH-467
      is a bi-functional enzyme showing both alpha2,3-sialyltransferase and alpha2,3
      linkage specific sialidase activity. To date, the crystal structures of several
      sialyltransferases have been solved, but the roles of amino acid residues around
      the catalytic site have not been completely clarified. Hence we performed a
      mutational study using alpha2,3-sialyltransferase cloned from P. phosphoreum JT
      ISH-467 as a model enzyme to study the role of the amino acid residues around the
      substrate-binding site. It was found that a mutation of the glutamic acid at
      position 342 in the sialyltransferase resulted in a loss of sialidase activity,
      although the mutant showed no decrease in sialyltransferase activity. Based on
      this result, it is strongly expected that the Glu342 of the enzyme is an
      important amino acid residue for sialidase activity.

PMID- 22972325
TI  - Labeling of polyethylenimine with fluorescent dye to image nucleus, nucleolus,
      and chromosomes in digitonin-permeabilized HeLa cells.
AB  - The visualization of nuclear architecture, which changes dynamically depending on
      the physiological and the pathological situation, remains an important challenge.
      Here we report that exposure of fluoresceinisothiocyanate-labeled
      polyethylenimine (FITC-PEI) to digitonin-permeabilized cervical cancer HeLa cells
      enable rapid detection of the morphology of the nuclear rim, the nucleolus, and
      mitotic chromosomes. This simple detection strategy can aid in scientific
      investigation for both basic research and diagnostic purposes.

PMID- 22972326
TI  - An adhesin-like protein, Lam29, from Lactobacillus mucosae ME-340 binds to
      histone H3 and blood group antigens in human colonic mucus.
AB  - A cell-surface 29-kDa protein (Lam29, cysteine-binding protein of the ABC
      transporter) from Lactobacillus mucosae ME-340 showed an adhesin-like property
      for human ABO blood group antigens expressed on the gastrointestinal mucosa. In
      addition, here we report that Lam29 also bound to an 18-kDa protein on human
      colonic mucus. By ligand blot assay and N-terminal amino acid sequence of the
      protein, it was identified as human histone H3. By ligand blot and microplate
      binding assays with recombinant histone H3, binding between Lam29 and histone H3
      was confirmed. The adhesion of ME-340 cells to histone H3 was significantly
      inhibited by 26% after the addition of 2.5 mg/mL Lam29 as compared to the absence
      of Lam29 (p<0.01). By GHCl extraction and transcription attenuation of ME-340
      cells, binding reduction of ME340 cells against histone H3 was detected at 12%
      and 13% respectively, as compared to control cells by the BIACORE assay (p<0.01).
      These data indicate that Lam29 shows multiple binding activities to blood group
      antigens and histone H3 in human colonic mucus. This is the first report to
      indicate that lactobacilli expressing Lam29 adhere to histone H3 on
      gastrointestinal mucosa.

PMID- 22972327
TI  - Citronellal ingestion decreases the appeal of male mouse urinary pheromone for
      female mice.
AB  - To determine whether ingestion of citronellal decreases the attractive power of
      the male mouse urinary odor, female mice were used in preference tests. A series
      of tests revealed that the female mice preferred voided urine odors from aged
      mice over those from younger adult mice. However, exogenous citronellal directly
      inhibited the advantage of the aged males with regard to attraction.

PMID- 22972328
TI  - Identification of des-methyl-DIF-1 methyltransferase in Dictyostelium purpureum.
AB  - The signalling molecule 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1
      one (DIF-1) is required for differentiation and pattern formation in
      Dictyostelium discoideum development. DIF-1 is synthesized by three enzymes, a
      hybrid polyketide synthase, a flavin-dependent halogenase, and a des-methyl-DIF-1
      methyltransferase. The genome data on the related species D. purpureum are now
      public. Using this genome information, des-methyl-DIF-1 methyltransferase of D.
      purpureum was identified, and was named Dp dmtA. Overexpression of Dp dmtA
      complemented the defects in basal disc formation and lower cup formation in a
      dmtA knock-out mutant of D. discoideum. This indicates that Dp dmtA has the same
      function as D. discoideum dmtA and compensates for loss of the dmtA gene in the
      D. discoideum dmtA mutant. The materials released in the medium by D. purpureum
      contained stalk-inducing activity with the same retention time as that of DIF-1
      in HPLC fractionation. This indicates that the stalk-inducing signal of DIF-1 and
      des-methyl-DIF-1 methyltransferase are conserved in D. purpureum.

PMID- 22972329
TI  - Transcriptome analyses of metabolic enzymes in thiosulfate- and hydrogen-grown
      Hydrogenobacter thermophilus cells.
AB  - Hydrogenobacter thermophilus is a chemolithoautotroph that utilizes not only
      hydrogen (H(2)) but also thiosulfate as sole source of energy and assimilates
      carbon dioxide via the reductive tricarboxylic acid (RTCA) cycle. We
      systematically carried out transcriptome analysis of metabolic enzymes in both
      H(2)- and thiosulfate-grown H. thermophilus cells. The analysis indicated that
      the expression of hydrogenase genes is repressed under thiosulfate oxidation
      conditions as compared with H(2) oxidation conditions. This was confirmed by
      enzyme assay. In contrast, some genes for sulfur metabolism, including sox genes,
      showed almost the same expression levels under both conditions. In addition, the
      genes for the RTCA cycle showed high expression levels under both conditions. It
      was suggested that sulfur metabolism and the RTCA cycle function as forms of
      basal metabolism, and H(2) oxidation is inducible. Switching of H(2) oxidation
      can be advantageous for the lifestyle of this bacterium in nature.

PMID- 22972330
TI  - MAP kinases, MPK9 and MPK12, regulate chitosan-induced stomatal closure.
AB  - Chitosan (CHT)-induced stomatal closure was inhibited by an MAPKK inhibitor,
      PD98059, and was impaired in mpk9 mpk12 but not in mpk9 or mpk12. CHT induced the
      production of reactive oxygen species, cytosolic alkalization, and cytosolic
      Ca(2+) oscillation in mpk9 mpk12. These results suggest that MPK9 and MPK12 are
      involved in CHT-induced stomatal closure.

PMID- 22972331
TI  - Isolation and screening of glycolipid biosurfactant producers from sugarcane.
AB  - Forty-three fungal producers for glycolipid biosurfactants, mannosylerythritol
      lipids (MELs), were isolated from leaves and smuts of sugarcane plants. These
      isolates produced MELs with sugarcane juice as nutrient source. The strains were
      taxonomically categorized into the genera Pseudozyma and Ustilago on the basis of
      partial sequences of the ribosomal RNA gene.

PMID- 22972332
TI  - YdfH identified as a repressor of rspA by the use of reduced genome Escherichia
      coli MGF-01.
AB  - We have reported the construction of 1 Mb reduced genome Escherichia coli MGF-01
      by a 28-step operation. This time, transcriptome analysis of MGF-01 was
      performed. Although the transcriptome profiles of the exponential phase in
      parental strain W3110red were well-conserved in MGF-01, the rspAB operon was
      highly expressed. A LacZ reporter assay of a series of stepwise deletion strains
      prepared in the course of MGF-01 construction indicated that rspA was highly
      expressed after the 5th step. Further analysis indicated that Delta29, one of the
      deleted regions at the 5th step, relates to an increase in rspA expression, and
      that transcriptional regulator ydfH, in the Delta29 region, is responsible for
      the expression of rspA, gel shift assay indicated that YdfH bound directly to the
      upstream region of rspA. Based on these results, it was concluded that YdfH is a
      transcriptional repressor of the rspAB operon.

PMID- 22972333
TI  - Sodium-dependent uptake of glutamate by novel ApGltS enhanced growth under salt
      stress of halotolerant cyanobacterium Aphanothece halophytica.
AB  - Glutamate is a major free amino acid in cyanobacteria, but its transport
      properties remain largely unknown. In this study, we found that a halotolerant
      cyanobacterium, Aphanothece halophytica, contained a sodium dependent glutamate
      transporter (ApGltS). The deduced amino acid sequence of ApGltS exhibited low
      homology (18-19% identity) to GltS from Synechocystis sp. PCC 6803 (slr1145) and
      Escherichia coli. The predicted ApGltS consisted of 476 amino acid residues with
      a molecular weight of 50,976 Da. As analysed by hydropathy profiling, ApGltS
      contains 11 transmembrane segments. The ApgltS gene was isolated and expressed in
      E. coli ME9107, which is deficient in glutamate uptake. ME9107, expressing
      ApGltS, took up glutamate and its rates increased with increasing concentrations
      of NaCl. Kinetics studies revealed that ApGltS is a high-affinity glutamate
      transporter with a K(m) of about 5 uM. The presence of 0.5 M NaCl in the assay
      medium increased V(max) by about 3-fold. Competition experiments revealed that
      glutamate, glutamine, aspartate, and asparagine inhibited glutamate uptake. The
      level of mRNA for ApgltS was higher in A. halophytica grown at high salinity.
      Under high salinity conditions supplemented with glutamate, A. halophytica showed
      a significant increase in intracellular glycine betaine.

PMID- 22972334
TI  - Total syntheses of (-)- and (+)-boronolide and their plant growth-inhibitory
      activity.
AB  - Optically pure (+)- and (-)-boronolides were stereoselectively synthesized from
      yeast reductive products which had been obtained by yeast reduction of one common
      racemic substrate. The lactone structure of boronolide was constructed by Baeyer
      Villiger oxidation. The stereochemistry of the yeast reduction products was
      studied to obtain the stereocenters at 5 positions of the dodecanolides of (+)-
      and (-)-boronolides. The stereochemistry of the 6 and 7 positions was obtained by
      AD-mix-alpha or beta oxidation. The chiral center at the 8 position was
      constructed by employing (R)-(+)- or (S)-(-)-2-methyl-CBS-oxazaborolidine
      reduction or the Mitsunobu reaction. The plant growth-inhibitory activity against
      Echinochloa crusgalli L. of naturally occurring (+)-boronolide was higher than
      that of the (-)-boronolide.

PMID- 22972335
TI  - Efficient preparation of (R)-3-hydroxypentanenitrile with high enantiomeric
      excess by enzymatic reduction with subsequent enhancement of the optical purity
      by lipase-catalyzed ester hydrolysis.
AB  - An efficient chemo-enzymatic procedure for the synthesis of (R)-3
      hydroxypentanenitrile (1) with over 99% enantiomeric excess using two enzymatic
      reactions was successfully established. Initial enantioselective enzymatic
      reduction of 3-oxopentanenitrile with reductase S1 gave (R)-1 with an 81.5% ee
      which was then converted to (R)-1-(cyanomethyl) propyl n-butyrate (3b).
      Subsequent lipase-catalyzed enantioselective hydrolysis of 3b gave (R)-1 in a
      high yield with over 99% ee.

PMID- 22972336
TI  - A novel alkaline esterase from Sporosarcina sp. nov. strain eSP04 catalyzing the
      hydrolysis of a wide variety of aryl-carboxylic acid esters.
AB  - A novel esterase showing activity specific for esters of aryl-carboxylic acids
      was discovered in Sporosarcina sp. nov., which was identified by the 16S rDNA
      sequencing method in addition to morphological and physiological analyses. The
      aryl-carboxylesterase (named EstAC) was purified 780-fold from crude cell
      extracts by a 5-step procedure. EstAC was characterized as a monomeric protein
      with a molecular weight of 43,000, an optimum pH of around 9.0, and an optimum
      temperature of 40  degrees C. The pH optimum and the effects of inhibitors
      together with an internal amino acid sequence suggested that EstAC is a member of
      family VIII esterases. EstAC was found to be highly active on a wide variety of
      substrates such as alkyl benzoates, alkyl phenylacetates, ethyl alpha- or beta
      substituted phenylpropionates, dialkyl terephthalates, dimethyl isophthalate, and
      ethylene glycol dibenzoate. However, monomethyl terephthalate was not hydrolyzed.
      It was suggested that EstAC had 4-hydroxybenzoyl and cinnamoyl esterase
      activities as well.

PMID- 22972337
TI  - Synthesis of sphingolipids with an omega-esterified long acyl chain, ceramide
      components of the human epidermis.
AB  - Esterified ceramides, (2S,3R,4E)-2-[(30'-stearoyloxy)triacontanamido]octadec-4
      ene-1,3-diol (2) and (2S,3R,4E,6R)-2-[(30'-stearoyloxy)triacontanamido]octadec-4
      ene-1,3,6-triol (4), are minor components of the human stratum corneum. We
      synthesized these ceramides by employing olefin cross metathesis as the key
      reaction for constructing their omega-hydroxytriacontanoyl part (13).

PMID- 22972338
TI  - Different impacts of purified and nonpurified diets on microbiota and toll-like
      receptors in the mouse stomach.
AB  - We compared the colonization of lactobacilli in the stomachs of mice fed
      nonpurified and purified diets and examined to determine whether the expression
      of Toll-like receptor 2, which is involved in the recognition of lactobacilli, is
      influenced by diet. Female BALB/c mice were fed a nonpurified or a purified diet
      for 2 weeks. Conventional cultivation and cultivation-independent molecular
      biological analysis based on the 16S rRNA gene sequence revealed that the number
      of lactobacilli associated with the gastric tissue was significantly higher in
      the mice fed the nonpurified diet than in those fed the purified diet. Sequencing
      analysis indicated that L. gasseri and L. johnsonii were predominant
      Lactobacillus species associated with the gastric tissue of the mice fed the
      nonpurified diet. The mRNA levels of Toll-like receptor 2, but not of 9, in the
      gastric tissue were significantly higher in the mice fed the purified diet than
      in those fed the nonpurified diet. We propose that nonpurified and purified diets
      have different impacts on gastric microbiota, which can in turn influence the
      expression of Toll-like receptor 2 in the stomach.

PMID- 22972339
TI  - Proton transfer in a reaction catalyzed by onion lachrymatory factor synthase.
AB  - We produced a single deuterated lachrymatory factor (propanthial S-oxide, m/z =
      91) in a model reaction system comprising purified alliinase, lachrymatory factor
      synthase (LFS), and (E)-(+)-S-(1-propenyl)-L-cysteine sulfoxide ((E)-PRENCSO) in
      D(2)O. Onion LFS reacted with the degraded products of (E)-PRENCSO by alliinase,
      but not with those of (Z)-PRENCSO. These findings indicate that onion LFS is an
      (E)-1-propenylsulfenic acid isomerase.

PMID- 22972340
TI  - Advanced glycation endproducts stimulate renal epithelial cells to release
      chemokines that recruit macrophages, leading to renal fibrosis.
AB  - Diabetic nephropathy is a major complication of diabetes and tubulointerstitial
      fibrosis is one of its manifestations. This study aimed to clarify the
      pathogenicity of advanced glycation endproducts (AGEs) toward NRK-52E, a tubular
      epithelial cell line. The AGE-exposed cells significantly increased gene
      expression of transforming growth factor beta, plasminogen activator inhibitor-1,
      and tissue transglutaminase, and a medium conditioned by them showed strong
      potential to recruit macrophages, partly through a chemokine, monocyte
      chemoattractant protein-1. Albumin denatured by maintenance at 37  degrees C for
      120 d exhibited similar activities, but they were lower than those of the AGEs.
      Thus, AGEs generated in diabetic patients might exacerbate fibrosis in the
      kidneys directly through renal epithelial cell stimulation, and indirectly by
      recruitment of macrophages.

PMID- 22972341
TI  - Glycoglycerolipids isolated from marine derived Streptomyces coelescens PK206-15.
AB  - Glycoglycerolipids were isolated from seaweed-associated marine actinomycete
      strain PK206-15, which was identified as Streptomyces coelescens based on 16S
      rDNA sequence analysis. The compounds were isolated by silica gel chromatography
      and high performance liquid chromatography. The structures were analyzed by
      nuclear magnetic resonance, high resolution-electrospray ionization-mass
      spectrometry, and methanolysis. The compounds were identified as 2R-1,2-di-12
      methylhexadecanoic acid-3-O-[beta-D-galactopyranosyl-(1''-6')-O-beta-D
      galactopyranosyl]-glycerol, 2R-1-12-methylhexadecanoic acid-2-hydroxyl-3-O-[beta
      D-galactopyranosyl-(1''-6')-O-beta-D-galactopyranosyl]-gly cerol, 2R-1,2-di-12
      methylhexadecanoic acid-3-O-beta-D-galactopyranosyl-glycerol, and 2R-1,2-di-14
      methylhexadecanoic acid-3-O-beta-D-galactopyranosyl-glycerol. These were active
      against the following fouling organisms: zoospores of Ulva pertusa, the diatom
      Navicula annexa, the mussel Mytilus edulis, and fouling bacteria with an EC(50)
      range of 0.005-0.2 ug/mL.

PMID- 22972342
TI  - Determination of the geographical origin of kimchi by (1)H NMR-based metabolite
      profiling.
AB  - Kimchi is a well-known traditional Korean food. Its geographical origins can be
      determined by its biochemical composition. This study identified the biochemical
      compositions of kimchi extracts from Korea and China by (1)H nuclear magnetic
      resonance (NMR) spectroscopy followed by multivariate data analysis. Principal
      component analyses (PCA) clearly discriminated between extracts prepared in the
      two countries. The identified metabolites, including amino acids, organic acids,
      sugars, and ethanol, contributed to discriminating the geographical origin of
      kimchi extracts. Furthermore, differences in composition by origin were predicted
      with high accuracy in external validation models. These results establish
      biochemical profiles for kimchi extracts, and indicate that metabolomics can be
      used in the discrimination of food origins.

PMID- 22972343
TI  - New chrodrimanin congeners, chrodrimanins D-H, from YO-2 of Talaromyces sp.
AB  - Four new meroterpenoids, named chrodrimanins D-G (4-7), and one known compound,
      renamed chrodrimanin H (8), were isolated from okara (the insoluble residue of
      whole soybean) that had been fermented with the YO-2 strain of Talaromyces sp.
      Their structures were elucidated by spectroscopic methods. Chrodrimanins D (4), E
      (5), and F (6) showed insecticidal activity against silkworms with respective
      LD(50) values of 20, 10, and 50 ug/g of diet.

PMID- 22972344
TI  - Structural characteristics of active and inactive glutamate dehydrogenases from
      the hyperthermophile Pyrobaculum islandicum.
AB  - The enzymes from hyperthermophiles are generally extremely thermostable and lose
      little or no activity during long periods under a variety conditions. This high
      stability is very attractive, in that it gives the enzymes potential for use in
      numerous bioprocesses. My research group has investigated this high stability
      from the viewpoint of the relationship between function and structure. In this
      review, I describe the molecular mechanism underlying the extreme stability of
      unboiled NAD-dependent glutamate dehydrogenase from the hyperthermophile
      Pyrobaculum islandicum. I also describe the activation of the inactive
      recombinant enzyme produced in mesophilic Escherichia coli from the viewpoint of
      the relationship between structure and activity.

PMID- 22972345
TI  - ATP-dependent export of neutral amino acids by vacuolar membrane vesicles of
      Saccharomyces cerevisiae.
AB  - Amino acid analysis of Saccharomyces cerevisiae cells indicated that neutral
      amino acids such as glycine and alanine were probably excluded from the vacuoles,
      and that vacuolar H(+)-ATPase (V-ATPase) was involved in the vacuolar
      compartmentalization of these amino acids. We found that vacuolar membrane
      vesicles export neutral amino acids in an ATP-dependent manner. This is important
      in identifying vacuolar transporters for neutral amino acids.

PMID- 22972346
TI  - Expression of a novel sphingosine 1-phosphate receptor motif protein gene in
      maturing rat testes.
AB  - We screened a novel sphingosine 1-phosphate receptor type 5 motif-containing
      gene, LOC290876, from maturing rat testes by differential display. Gene
      expression was testis-specific, increased at week 7, and continued for 15 weeks.
      PCR analysis clarified two gene transcript isoforms, which were expressed at the
      same level in all samples detected in Northern blot. The deduced amino acid
      sequences of the two isoforms revealed differences in carboxyl terminal
      sequences. Gene and protein expression in the testes was dominant in the
      spermatocytes, and protein expression was localized to the nucleus. Taken
      together, these findings suggest that the LOC290876-encoded gene product is not
      involved in sphingosine signaling, but has distinct roles in the nucleus during
      the processes of spermatocyte maturation and meiosis producing spermatids.

PMID- 22972347
TI  - Physiological effects and tissue distribution from large doses of tocotrienol in
      rats.
AB  - Supplementation to an AIN93G-based diet of tocotrienol (T3) for 13 weeks
      administered to Fischer 344/slc rats showed a safety profile with no side
      effects. Dose-dependent T3 levels were detected in many tissues. Under the
      present experimental conditions, a continuous intake of the T3 concentrate would
      be safe in the rats as long as the T3 content was less than 0.20% of the dietary
      intake.

PMID- 22972348
TI  - Trans fatty acid intake and serum cholesterol levels in young Japanese women.
AB  - There are very limited data concerning the influence of low-level trans fatty
      acid (TFA) intake on blood lipid levels. In this study, correlation of total and
      diene TFA intake with serum cholesterol levels was studied in young Japanese
      women. The mean intakes of total and diene TFAs were 0.36% and 0.05% of energy,
      respectively. There was a significant correlation between total fat intake and
      TFA intake. TFA intake was significantly correlated with erythrocyte TFA content.
      Total TFA intake was not correlated with total, LDL- or HDL-cholesterol levels.
      No correlatuon was found between diene TFA intake and cholesterol level. Total
      and diene TFA intake were not correlated with hemoglobin A1c or C-reactive
      protein levels. These results suggest that the average TFA intake of young
      Japanese women does not adversely affect serum cholesterol levels.

PMID- 22972349
TI  - Enhancing effect of IMP on myosin and actin extraction from porcine meat.
AB  - We examined the effects of nucleoside monophosphates on the dissociation of
      actomyosin into myosin and actin. GMP was effective only among GMP, CMP, dTMP,
      and UMP. Hence we concluded that purine-based nucleoside monophosphates such as
      GMP, AMP, and IMP are effective, incorporating this with our previous results
      (Okitani A et al., Biosci. Biotechnol. Biochem., 72, 2005-2011 (2008)). Then we
      examined whether IMP enhances the extraction of myosin and actin as well as
      pyrophosphate (KPP), using homogenates of pork with 9 volumes of 0.3, 0.4, and
      0.5 M NaCl solutions containing 0-36 mM IMP or 0-9 mM KPP. Maximum
      extractability, about 70% for both proteins, was attained by means of NaCl
      solutions containing 36 mM IMP. These values were comparable to the maximum
      values, about 90% for myosin and 50% for actin, attained by means of solutions
      containing 9 mM KPP. Hence we concluded that IMP enhances the extraction of
      myosin and actin from porcine meat.

PMID- 22972350
TI  - Search for cell-wall-degrading enzymes of world-wide rice grains by PCR and their
      effects on the palatability of rice.
AB  - Such rice cultivars as Japonica, Japonica-Indica hybrid, Javanica and Indica,
      were evaluated for their main chemical components (amylose content and protein
      content), pasting property of rice flour (consistency), physical property of the
      cooked rice grains (adhesion, L3), and enzyme activities (cellulase and
      xylanase). The amylose content, cellulase activity and xylanase activity showed
      significant positive or negative correlation with the pasting property
      (consistency) of rice flour (r = 0.89, r = 0.58, r = 0.70, respectively) and with
      the physical property of the cooked rice grains (adhesion, L3: r = -0.51, r = 
      0.61, r = -0.71, respectively) at the level of 1%. Endogenous xylanase and
      cellulase played important roles to determine the texture of the cooked rice
      grains similarly to the amylose content. Part of the DNA sequences of the alpha
      glucosidase gene differed among the Japonica, Japonica-Indica hybrid and Indica
      subspecies. We found discriminative DNA bands appearing by PCR, corresponding to
      1,4-beta-xylanase and endo-1,4-beta-glucanase 13 in the case of Indica rice,
      Indica-Japonica hybrid rice, and Javanica rice (non-Japonica subspecies). The
      equation for estimating the physical property (adhesion) of cooked rice grains by
      PCR was improved by adding novel primers related to the cell-wall-degrading
      enzymes.

PMID- 22972351
TI  - Molecular cloning, expression, and characterization of starfish DNA (cytosine-5)
      methyltransferases.
AB  - To determine whether and if so how a DNA methylation-dependent epigenetic
      mechanism for transcriptional gene silencing functions in Echinoderms, we cloned
      and sequenced dnmt1 and dnmt3 cDNAs of the starfish Asterina pectinifera. Since
      the Strongylocentrotus purpuratus genome has only two loci of DNA (cytosine-5)
      methyltransferase genes encoding Dnmt1 and Dnmt3, they might constitute a
      sufficient set of dnmt genes in Echinoderms. The starfish Dnmt3 whose cDNA we
      cloned showed highest homology to a mammalian Dnmt3a2 splicing variant.
      Essentially all the characteristic motifs and sequences of the mammalian
      counterparts were found in the starfish Dnmts as well, except that a typical PCNA
      binding domain motif was lacking in the starfish Dnmt1. RT-PCR analysis indicated
      that the dnmt1 mRNA exists in both ovary and oocytes, but its levels in other
      tissues were very low or almost negligible. In contrast, the dnmt3 mRNA was
      detected only in the ovary, and not at all in the oocytes. The size of a dnmt1
      transcript was about 6.5 kb on Northern blot analysis. On heterologous
      expression, the starfish Dnmt1 protein was expressed in insect cells in
      catalytically active form.

PMID- 22972352
TI  - Antihypertensive effect of boysenberry seed polyphenols on spontaneously
      hypertensive rats and identification of orally absorbable proanthocyanidins with
      vasorelaxant activity.
AB  - The antihypertensive effect of a single oral administration of a boysenberry seed
      polyphenol extract to spontaneously hypertensive rats was evaluated at different
      doses (100 and 200 mg/kg), and a significant decrease in systolic blood pressure
      (SBP) was observed up to 6 h post administration. The extract was separated into
      proanthocyanidin-rich and ellagitannin fractions by solvent partition. A
      significant decrease in SBP was observed only after administering the
      proanthocyanidin-rich fraction, and this decrease was abolished by an N(G)-nitro
      L-arginine methyl ester (L-NAME) injection. An analysis of the orally absorbable
      components showed that intact dimeric and trimeric procyanidins and
      propelargonidins were detectable in the plasma with a maximal concentration 2 h
      post administration. The vasorelaxant activity of the extract was also confirmed
      by in vitro assay using rat aorta rings. These results suggest that
      proanthocyanidins (PAs) in boysenberry seeds may have played an important role in
      the observed antihypertensive effect.

PMID- 22972353
TI  - Purification and characterization of a highly thermostable chitinase from the
      stomach of the red scorpionfish Scorpaena scrofa with bioinsecticidal activity
      toward cowpea weevil Callosobruchus maculatus (Coleoptera: Bruchidae).
AB  - This present study is the first attempt to report on the purification and
      characterization of a chitinase from the stomach of the red scorpionfish
      Scorpaena scrofa. A 50-kDa chitinase (SsChi50) was purified to homogeneity, and
      matrix assisted laser desorption ionization-time of flight/mass spectrometry
      (MALDI-TOF/MS) analysis showed that SsChi50 was a monomer with a molecular mass
      of 50,103 Da. The 25 N-terminal residues of SsChi50 displayed high homology with
      family-18 chitinases. Optimal activity was obtained at pH 5.0 at 80  degrees C.
      SsChi50 was stable at pH and temperature ranges of 3.0 to 7.0 and 70 to 90 
      degrees C for 48 and 4 h respectively. Among the inhibitors and metals tested, p
      chloromercuribenzoic acid, N-ethylmaleimide, Hg(2+), and Hg(+) completely
      inhibited enzyme activity. Chitinase activity was high on colloidal chitin,
      glycol chitin, glycol chitosane, chitotriose, and chitooligosaccharide. Chitinase
      activity towards synthetic substrates in the order of p-NP-(GlcNAc)(n) (n = 2-4)
      was p-NP-(GlcNAc)(2) > p-NP-(GlcNAc)(4) > p-NP-(GlcNAc)(3). Our results suggest
      that the SsChi50 enzyme preferentially hydrolyzed the second glycosidic link from
      the non-reducing end of (GlcNAc)(n). This enzyme obeyed Michaelis-Menten
      kinetics, the K(m) and k(cat) values being 0.412 mg, colloidal chitin mL(-1) and
      5.33 s(-1) respectively. An in vivo bioinsecticidal assay was developed for
      SsChi50 against Callosobruchus maculatus adults. The enzyme showed
      bioinsecticidal activity toward Callosobruchus maculatus, indicating the
      possibility of using it in biotechnological strategies for insect management for
      stored cowpea seeds.

PMID- 22972354
TI  - Practical removal of radioactivity from soil in Fukushima using immobilized
      photosynthetic bacteria combined with anaerobic digestion and lactic acid
      fermentation as pre-treatment.
AB  - Practical removal of radioactivity from polluted soil in Fukushima, Japan was
      done using a photosynthetic bacterium, Rhodobacter sphaeroides SSI, immobilized
      in alginate beads. The beads were put in a mesh bag and soaked in which soil was
      suspended (5 kg of soil/10 L of tap water). The radioactivity of the broth
      decreased by 31% after 15 d of aerobic treatment. When lactic acid bacterial
      culture broth was added to the suspend broth, about 50% of the radioactivity was
      transferred to a suspend broth fraction consisting of small particles from the
      soil after 3 d of fermentation and 20 s of sedimentation. The results suggest
      that organic matter in the soil was decomposed by anaerobic digestion and lactic
      acid fermentation simultaneously, and was then transferred into the liquid as
      small particles. With combined treatment by anaerobic digestion and lactic acid
      fermentation for 5 d and immobilized bead aerobic treatment for an additional 19
      d, the radioactivity of suspend broth decreased by 66%. The radioactivity of the
      original soil (10.56 uSv/h) ultimately decreased by 67% (3.52 uSv/h) after the
      combined treatment.

PMID- 22972355
TI  - [Inflammatory choroidal neovascularisations].
AB  - Inflammation plays a key role in the induction of choroidal neovascular membranes
      (CNV). This explains why each form of posterior uveitis may lead to CNV
      formation. Diseases like presumed ocular histoplasmosis syndrome (POHS),
      multifocal choroiditis (MFC) or punctate inner choroidopathy (PIC) carry a high
      risk of CNV creation. Inflammatory processes mostly cause classical membranes.
      Because of the classical membrane form, smaller membrane size and the younger age
      of the patients' inflammatory membranes are often better treatable than membranes
      in AMD patients. In the times before VEGF inhibition inflammatory membranes were
      treated with argon laser coagulation and later with PDT. Nowadays better visual
      acuity results are achievable through VEGF inhibitor injections with or without
      PDT. This is proven by a few publications with greater numbers of patients
      because of the rarity of the diseases and several case reports in the literature.
      In addition to CNV treatment the control of intraocular inflammation should never
      be forgotten because it forms the leading CNV trigger.

PMID- 22972356
TI  - [Infections after intraocular lens surgery: implications for refractive surgery].
AB  - Apart from the classical indication of removing an opaque lens that is
      compromising vision, extraction of the crystalline lens is gaining increasing
      importance as a refractive procedure. This literature review which considers the
      present guidelines of various ophthalmological societies and recently published
      studies is intended to give an estimate of the incidence of postoperative
      endophthalmitis and evidence-based recommendations for its prophylaxis,
      diagnosis, and therapy. The incidence of endophthalmitis after cataract
      extraction is reported to be 0.04% to 0.3% in most sizeable studies. Immediate
      sequential bilateral cataract surgery is internationally gaining popularity. It
      remains difficult to estimate whether or not the risk of endophthalmitis is
      affected with this approach. A toxic anterior segment syndrome (TASS) needs to be
      differentiated from postoperative endophthalmitis. TASS is an acute sterile
      inflammation after cataract surgery. Remnants of detergents and antiseptics on
      the surgical instruments are supposed to be main triggers. Additionally, the
      inappropriate preparation of solutions and antibiotics for intracameral use is
      considered to be a major cause. A case of TASS was also reported after
      implantation of an iris-fixated anterior chamber lens in a phakic eye. The
      cefuroxime solution that was prophylactically used in the ESCRS study and that is
      recommended for routine cataract surgery is not commercially available in Germany
      as a ready preparation for intraoperative application. Different measures are
      undertaken in different countries to prevent postoperative endophthalmitis, whose
      values are not exactly quantifiable. Antisepsis with povidone-iodine is still
      considered to be the component with the best evidence. For management of acute
      postoperative endophthalmitis, the systemic application of antibiotics is
      recommended in addition to their intravitreal injection. Few case reports have
      been published describing an infection after the implantation of refractive
      intraocular lenses (IOLs) in a phakic eye. However, we could not find meaningful
      information regarding the incidence of endophthalmitis after implantation of
      refractive IOLs. Based on the fact that these IOLs are not implanted into the
      capsular bag but in front of the crystalline lens or into the anterior chamber,
      and the presumably better anti-microbial immunity of this younger population
      compared to cataract patients, one may assume that the infection rate is lower
      than after cataract surgery. Nevertheless, a prospective register to document all
      endophthalmitis cases is desirable.

PMID- 22972357
TI  - [How does central cornea thickness influence intraocular pressure during
      applanation and contour tonometry?].
AB  - BACKGROUND: Golmann applanation tonometry represents a well-established procedure
      for measuring intraocular pressure (IOP). This implies the necessity of an
      accurate measurement of IOP with the reference tonometer. One example is the
      contour tonometer Pascal with a measuring probe, adapted to the cornea geometry,
      for measuring the IOP and the ocular pulse amplitude. There is controversy of how
      strongly corneal thickness affects the measurement of IOP. We thus analysed, for
      a number of eyes, the correlation of IOP, as measured by two types of applanation
      tonometers and one contour tonometer and the central corneal thickness. METHODS:
      In all 158 patient eyes were investigated in a clinical comparison of applanation
      tonometers AT 870 and Ocuton-A. The study was performed by a trained
      ophthalmologist and the comparison was in accordance with international standard
      ISO 8612. In addition, the corneal thickness in the vertex was repeatedly
      determined using an Oculus Pentacam. The potential effect of central corneal
      thickness on the IOP as measured by the mentioned tonometers was statistically
      evaluated by rank correlation analysis. RESULTS: We found that the measured IOP
      values for the three investigated tonometers were not normally distributed. The
      central corneal thickness values, in contrast, measured on 158 eyes by means of
      an ultrasound pachymeter and additionally on 235 eyes by the Pentacam, obeyed a
      Gaussian distribution. For the correlation analysis of both parameters the
      Spearman linear rank correlation coefficient (r) was considered. We found a very
      weak (|r| < 0.2) correlation between central corneal thickness and IOP for all 3
      tonometers. The softness of the correlation is also illustrated by a large
      standard deviation of the regression line. A comparison of the different devices
      for corneal-thickness measurements shows less variance and a smaller variation
      coefficient when the ultrasoundpachymeter AL-1000 is used. CONCLUSIONS: The
      measured values for IOP are only very weakly correlated to the central corneal
      thickness. For the 3 tonometer types studied there is no need to correct the
      indicated pressure values according to the central corneal thickness of the
      investigated eye. Clinical comparisons according to the ISO 8612 standard between
      a tonometer under test and a reference Goldmann applanation tonometer are always
      a time-consuming procedure. Additional measures to determine the central corneal
      thickness of every investigated eyes are dispensable.

PMID- 22972358
TI  - Structures and properties of lanthanide metal-organic frameworks based on a 1,2,3
      triazole-containing tetracarboxylate ligand.
AB  - A family of 3D lanthanide metal-organic frameworks, [La(HTADIP)(H(2)O)(4)].xH(2)O
      (2 < x < 2.5) (1), [Eu(HTADIP)(H(2)O)(4)].H(2)O (2),
      [Tb(HTADIP)(H(2)O)(3)].2H(2)O (3), and [Er(HTADIP)(H(2)O)(3)].2H(2)O (4)
      (H(4)TADIP = 5,5'-(1H-1,2,3-triazole-1,4-diyl)diisophthalic acid), have been
      hydrothermally synthesized and characterized. The unsymmetrical 1,2,3-triazole
      containing tetracarboxylate ligand was synthesized through the copper-catalyzed
      azide-alkyne cycloaddition (CuAAC) reaction of diethyl-5-azidoisophthalate (M1)
      and diethyl-5-ethynylisophthalate (M2). Single-crystal X-ray diffraction analyses
      for 1-4 reveal that they are isostructural. These compounds crystallize in the
      monoclinic P2(1)/c space group with the rutile topology. The luminescent
      properties of compounds 2 and 3 were investigated and characteristic Eu(III) and
      Tb(III) emissions are observed. Compound 3 exhibits selective luminescent sensing
      behavior for Cu(2+) ions in aqueous solution. The magnetic properties of
      compounds 3 and 4 were studied.

PMID- 22972359
TI  - Protective effect of Azadirachta indica extract against Eimeria papillata-induced
      coccidiosis.
AB  - Coccidiosis in poultry is caused by protozoan parasites of the genus Eimeria,
      which is responsible for worldwide economic losses. The methanolic extract of
      Azadirachta indica (neem) leaves was used in vivo for its pharmacological,
      antioxidant, and anticoccidial properties. Four groups of mice were investigated.
      The first group was inoculated only with sterile saline and served as the control
      group. The second group was treated by oral gavage with neem extract (500 mg/kg)
      daily for 4 days. The third and fourth groups were infected with 10(3) sporulated
      oocysts of Eimeria papillata. The fourth group was also treated once daily with
      neem extract for 4 days. Paraffin sections from the jejunum as well as jejunal
      homogenate were prepared for the histopathological and biochemical
      investigations, respectively. The data showed that mice infected with E.
      papillata revealed an output of 6.5 * 10(5) +/- 29,753 oocysts per gram feces on
      day 4 postinoculation. This output is significantly decreased to 2.7 * 10(5) +/-
      37,341 oocysts in neem-treated mice. Infection with E. papillata induced marked
      histopathological alterations in the jejunum in the form of inflammation,
      vacuolation of the epithelium, and destruction of some villi. Also, the neem
      extract greatly diminished body weight loss of infected mice. Moreover, the
      number of goblet cells stained with Alcian blue within the infected villi was
      significantly lowered (P <= 0.05). In addition, E. papillata enhanced lipid
      peroxidation and nitric oxide production in both serum and jejunum with
      concomitant reduction in glutathione. Neem induced marked improvements in all of
      the studied parameters as well as the histopathological features of the jejunum.
      Our study revealed that neem as a natural product has protective effects against
      E. papillata-induced coccidiosis.

PMID- 22972360
TI  - Adipogenic differentiation of scaffold-bound human adipose tissue-derived stem
      cells (hASC) for soft tissue engineering.
AB  - Adipose tissue engineering, instead of tissue substitution, often uses autologous
      adipose tissue-derived stem cells (hASC). These cells are known to improve graft
      integration and to support neovascularization of scaffolds when seeded onto
      biomaterials. In this study we thought to engineer adipose tissue using scaffold
      bound hASC, since they can be differentiated into the adipocyte cell lineage and
      used for soft tissue regeneration. We show here by microscopy and gene expression
      of the peroxysome proliferator-activated receptor gene (PPARgamma2) that hASC
      growing on polypropylene fibrous scaffolds as well as on three-dimensional
      nonwoven scaffolds can be turned into adipose tissue within 19 days. Freshly
      isolated hASC displayed a higher differentiation potential than hASC cultured for
      eight passages. In addition, we proved a modified alginate microcapsule to
      directly induce adipogenic differentiation of incorporated hASC. The results may
      help to improve long-term success of adipose tissue regeneration, especially for
      large-scale soft tissue defects, and support the development of cell-scaffold
      combinations which can be shaped individually and directly induce the adipogenic
      differentiation of incorporated hASC at the site of implantation.

PMID- 22972361
TI  - The tradeoff between torpor use and reproduction in little brown bats (Myotis
      lucifugus).
AB  - In mammals, reproduction, especially for females is energetically demanding.
      Therefore, during the reproductive period females could potentially adjust
      patterns of thermoregulation and foraging in concert to minimise the energetic
      constraints associated with pregnancy and lactation. We assessed the influence of
      pregnancy, lactation, and post-lactation on torpor use and foraging behaviour by
      female little brown bats, Myotis lucifugus. We measured thermoregulation by
      recording skin temperature and foraging by tracking bats which carried
      temperature-sensitive radio-tags. We found that individuals, regardless of
      reproductive condition, used torpor, but the patterns of torpor use varied
      significantly between reproductive (pregnant and lactating) females and post
      lactating females. As we predicted, reproductive females entered torpor for
      shorter bouts than post-lactating females. Although all females used torpor
      frequently, pregnant females spent less time in torpor, and maintained higher
      skin temperatures than either lactating or post-lactating females. This result
      suggests that delayed offspring development which has been associated with torpor
      use during pregnancy, may pose a higher risk to an individual's reproductive
      success than reduced milk production during lactation. Conversely, foraging
      behaviour of radio-tagged bats did not vary with reproductive condition,
      suggesting that even short, shallow bouts of torpor produce substantial energy
      savings, likely obviating the need to spend more time foraging. Our data clearly
      show that torpor use and reproduction are not mutually exclusive and that torpor
      use (no matter how short or shallow) is an important means of balancing the costs
      of reproduction for M. lucifugus.

PMID- 22972363
TI  - Photovoltaic efficiency enhancement by the generation of an embedded silica-like
      passivation layer along the P3HT/PCBM interface using an asymmetric block
      copolymer additive.
AB  - A new approach to improve the power conversion efficiency of polymer bulk
      heterojunction solar cells is demonstrated by generating a silica-like
      passivation layer embedded along the three-dimensionally intertwined interfaces
      between the nanoscopic domains of P3HT and PCBM by addition of an aymmetric block
      copolymer containing a short organo-silica precursor.

PMID- 22972362
TI  - Expression of genes involved in energy mobilization and osmoprotectant synthesis
      during thermal and dehydration stress in the Antarctic midge, Belgica antarctica.
AB  - The Antarctic midge, Belgica antarctica, experiences sub-zero temperatures and
      desiccating conditions for much of the year, and in response to these
      environmental insults, larvae undergo rapid shifts in metabolism, mobilizing
      carbohydrate energy reserves to promote synthesis of low-molecular-mass
      osmoprotectants. In this study, we measured the expression of 11 metabolic genes
      in response to thermal and dehydration stress. During both heat and cold stress,
      we observed upregulation of phosphoenolpyruvate carboxykinase (pepck) and
      glycogen phosphorylase (gp) to support rapid glucose mobilization. In contrast,
      there was a general downregulation of pathways related to polyol, trehalose, and
      proline synthesis during both high- and low-temperature stress. Pepck was
      likewise upregulated in response to different types of dehydration stress;
      however, for many of the other genes, expression patterns depended on the nature
      of dehydration stress. Following fast dehydration, expression patterns were
      similar to those observed during thermal stress, i.e., upregulation of gp
      accompanied by downregulation of trehalose and proline synthetic genes. In
      contrast, gradual, prolonged dehydration (both at a constant temperature and in
      conjunction with chilling) promoted marked upregulation of genes responsible for
      trehalose and proline synthesis. On the whole, our data agree with known
      metabolic adaptations to stress in B. antarctica, although a few discrepancies
      between gene expression patterns and downstream metabolite contents point to
      fluxes that are not controlled at the level of transcription.

PMID- 22972365
TI  - Cheyne-stokes respiration in chronic heart failure. Treatment with adaptive
      servoventilation therapy.
AB  - Sleep-disordered breathing (SDB) with predominant obstructive or central sleep
      apnea (OSA/CSA) with Cheyne-Stokes respiration (CSR) is a common, but
      underestimated and underappreciated, comorbidity in patients with heart failure
      (HF). Regardless of the type of HF (systolic or diastolic) or its etiology
      (ischemic, non-ischemic, valvular etc), the prevalence of SDB is remarkably high
      in this patient group, at 70-76%. Even more so in HF than in the general
      population, OSA and CSA in particular are independently associated with an
      impaired prognosis. This review details the pathophysiology of CSA-CSR in HF,
      highlights the challenges and tools available for diagnosis, explains the concept
      of adaptive servoventilation (ASV) therapy, and summarizes the existing
      literature on the use of ASV therapy in HF patients in general and HF with
      reduced ejection fraction in particular.

PMID- 22972364
TI  - Clustering of metabolic syndrome components attenuates coronary plaque regression
      during intensive statin therapy in patients with acute coronary syndrome: the
      JAPAN-ACS subanalysis study.
AB  - BACKGROUND: The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in
      Acute Coronary Syndrome) trial showed that intensive statin therapy could induce
      significant coronary plaque regression in acute coronary syndrome (ACS). We
      evaluated the impact of metabolic syndrome (MetS) and its components on coronary
      plaque regression in the JAPAN-ACS patients. METHODS AND RESULTS: Serial
      intravascular ultrasound measurements over 8-12 months were performed in 242 ACS
      patients receiving pitavastatin or atorvastatin. Patients were divided into
      groups according to the presence of MetS or the number of MetS components.
      Although the percent change in plaque volume (%PV) was not significantly
      different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was
      significantly associated with an increasing number of MetS components (component
      0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69;
      components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The
      percent change in body mass index (%BMI) significantly correlated with %PV
      (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017).
      In addition, %BMI was an independent predictor of plaque regression after
      adjustment for the changes of low- and high-density lipoprotein cholesterol,
      triglycerides and HbA(1c). CONCLUSIONS: The clustering of MetS components, but
      not the presence of MetS itself, could attenuate coronary plaque regression
      during intensive statin therapy in ACS patients. Therefore, to achieve a greater
      degree of plaque regression, it is necessary to treat to each MetS component and
      use lifestyle modification.

PMID- 22972366
TI  - Novel strategy to prevent atrial fibrosis and fibrillation.
AB  - To explore a novel strategy of preventing atrial fibrosis and atrial fibrillation
      (AF), we have established 3 appropriate experimental models of AF. Firstly,
      atrial fibrosis was induced by pressure overload by abdominal aortic constriction
      (AAC). AAC enhanced left atrial (LA) expression of monocyte chemoattractant
      protein-1. Scanning electron microscopy revealed that LA endothelial cells were
      irregularly hypertrophied, with disarrangement of lines of cells. Possible
      "arrested" leukocyte-derived cells were observed on the surface of LA endothelial
      cells. Treatment with pioglitazone, a peroxisome proliferator-activated receptor
      gamma agonist, resulted in attenuation of pressure overload-induced LA fibrosis.
      Secondly, LA fibrosis was induced by continuous infusion of angiotensin II (AII).
      Repeated whole-body hyperthermia led to the induction of heat shock protein (HSP)
      72, which resulted in attenuation of AII-induced LA fibrosis. Thirdly, atrial
      fibrosis was induced by 5/6 nephrectomy as a model of AF associated with chronic
      kidney disease. Because the amount of nicotinamide adenine dinucleotide phosphate
      oxidase was increased and the potent antioxidant agent was effective, oxidative
      stress may be involved in the pathogenesis of LA fibrosis and enhanced AF
      vulnerability in this model. These observations suggest that inflammatory
      profibrotic processes are essential for the development of atrial fibrosis in
      these 3 models. Pioglitazone, induction of HSPs and antioxidant agent could be
      novel therapeutic approaches to preventing atrial fibrosis and AF. 

PMID- 22972367
TI  - Multiaxial mechanical behavior of human fetal membranes and its relationship to
      microstructure.
AB  - This study was directed to the measurement of the mechanical response of fetal
      membranes to physiologically relevant loading conditions. Characteristic
      mechanical parameters were determined and their relation to the microstructural
      constituents collagen and elastin as well as to the pyridinium cross-link
      concentrations analyzed. 51 samples from twelve fetal membranes were tested on a
      custom-built inflation device, which allows mechanical characterization within a
      multiaxial state of stress. Methods of nonlinear continuum mechanics were used to
      extract representative mechanical parameters. Established biochemical assays were
      applied for the determination of the collagen and elastin content. Collagen cross
      link concentrations were determined by high-performance liquid chromatography
      measurements. The results indicate a distinct correlation between the mechanical
      parameters of high stretch stiffness and membrane tension at rupture and the
      biochemical data of collagen content and pyridinoline as well as
      deoxypyridinoline concentrations. No correlation was observed between the
      mechanical parameters and the elastin content. Moreover, the low stretch
      stiffness is, with a value of 105 +/- 31 * 10(-3) N/ mm much higher for a biaxial
      state of stress compared to a uniaxial stress configuration. Determination of
      constitutive model equations leads to better predictive capabilities for a
      reduced polynomial hyperelastic model with only terms related to the second
      invariant, I 2, of the right Cauchy-Green deformation tensor. Relevant insights
      were obtained on the mechanical behavior of fetal membranes. Collagen and its
      cross-linking were shown to determine membrane's stiffness and strength for
      multiaxial stress states. Their nonlinear deformation behavior characterizes the
      fetal membranes as I 2 material. 

PMID- 22972368
TI  - A simple model for estimating the active reactions of embryonic tissues to a
      deforming mechanical force.
AB  - Active reactions of embryonic tissues to mechanical forces play an important role
      in morphogenesis. To study these reactions, experimental models that enable to
      evaluate the applied forces and the deformations of the tissues are required. A
      model based upon the active intrusion of a living early gastrula Xenopus embryo
      into a tube half the embryo in diameter is described. The intrusion is initially
      triggered by a suction force of several dozen Pa but then continues in the
      absence of external driving force, stopping immediately after the entire embryo
      has penetrated into the tube. The process can be stopped by cytoskeletal drugs or
      by the damage of the part of the embryo still non-aspirated and is associated
      with the transversal contraction and meridional elongation of the non-aspirated
      part of the embryo surface and quasi-periodic longitudinal
      contractions/extensions of the cells within the part already aspirated. We
      suggest that this reaction is an active response to the embryo deformation and
      discuss its morphogenetic role. The problem of estimating the elastic modules of
      embryonic tissues is also discussed.

PMID- 22972369
TI  - Advanced non-small cell lung cancer (NSCLC): maintenance therapy for all?
AB  - OPINION STATEMENT: The standard of care for the treatment of patients with
      advanced NSCLC includes 4-6 cycles of platinum-doublet chemotherapy with or
      without bevacizumab, with modest improvements in survival. To improve upon
      outcomes, recent studies have investigated the role of maintenance therapy after
      first-line chemotherapy. This concept can be divided into continuation and switch
      maintenance. The majority of studies have shown significant improvements in
      progression-free survival (PFS) with the addition of maintenance, but the
      improved PFS has not always resulted in an improvement of overall survival (OS).
      Two notable exceptions are erlotinib and, for non-squamous NSCLC, pemetrexed. For
      patients with non-squamous NSCLC who respond or remain stable after four cycles
      of platinum-doublet chemotherapy, either continuation of pemetrexed (if included
      in the induction regimen) or switch to pemetrexed as maintenance has been shown
      to improve OS compared with observation. Whether maintenance pemetrexed improves
      OS compared with treatment with pemetrexed at progression is unknown. Recent
      trials suggest that maintenance therapy benefits both patients with initial
      response and stable disease after chemotherapy. There is insufficient evidence to
      support recommending the combination of pemetrexed and bevacizumab over
      maintenance pemetrexed alone as a switch maintenance approach, although the
      combination seems to be more effective than bevacizumab alone. The ongoing ECOG
      5508 trial is examining this question. For both squamous and non-squamous NSCLC,
      switch maintenance with erlotinib has been shown to improve both PFS and OS,
      although the improvement is modest. Switch maintenance with docetaxel or
      continuation maintenance with gemcitabine confers improvements in PFS regardless
      of histology but has failed to show improvements in OS. For this reason, switch
      maintenance with erlotinib can be considered in patients with squamous NSCLC.
      Overall, maintenance therapy may benefit patients with good performance status
      who complete four cycles of induction chemotherapy with manageable toxicity, but
      there is insufficient evidence to make this a blanket recommendation for
      everyone. Maintenance should remain an individual decision between patients and
      the treating oncologist.

PMID- 22972371
TI  - Editorial comment: Re: Brubaker L. Conflict of interest: what is the role of our
      professional societies? Neurourol Urodyn 2012;31:1217-1218.

PMID- 22972370
TI  - Blocking of p38 and transforming growth factor beta receptor pathways impairs the
      ability of tolerogenic dendritic cells to suppress murine arthritis.
AB  - OBJECTIVE: Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able
      to reduce inflammation when therapeutically administered into mice with collagen
      induced arthritis (CIA). The aim of this study was to uncover the mechanisms that
      define the tolerogenic effect of short-term LPS-modulated DCs on CIA. METHODS:
      Bone marrow-derived DCs were stimulated for 4 hours with LPS and characterized
      for their expression of maturation markers and their cytokine secretion profiles.
      Stimulated cells were treated with SB203580 or SB431542 to inhibit the p38 or
      transforming growth factor beta (TGFbeta) receptor pathway, respectively, or were
      left unmodified and, on day 35 after CIA induction, were used to inoculate mice.
      Disease severity was evaluated clinically. CD4+ T cell populations were counted
      in the spleen and lymph nodes from inoculated or untreated mice with CIA. CD4+
      splenic T cells were transferred from mice with CIA treated with LPS-stimulated
      DCs or from untreated mice with CIA into other mice with CIA on day 35 of
      arthritis. RESULTS: Treatment with LPS-stimulated DCs increased the numbers of
      interleukin-10 (IL-10)-secreting and TGFbeta-secreting CD4+ T cells, but
      decreased the numbers of Th17 cells. Adoptive transfer of CD4+ T cells from
      treated mice with CIA reproduced the inhibition of active CIA accomplished with
      LPS-stimulated DCs. The therapeutic effect of LPS-stimulated DCs and their
      influence on T cell populations were abolished when the p38 and the TGFbeta
      receptor pathways were inhibited. CONCLUSION: DCs modulated short-term (4 hours)
      with LPS are able to confer a sustained cure in mice with established arthritis
      by re-educating the CD4+ T cell populations. This effect is dependent on the p38
      and the TGFbeta receptor signaling pathways, which suggests the participation of
      IL-10 and TGFbeta in the recovery of tolerance.

PMID- 22972373
TI  - The reproducibility of measurements of differential renal function in paediatric
      99mTc-MAG3 renography:  is this correct?

PMID- 22972372
TI  - Apoptosis of K562 leukemia cells by Abnobaviscum F(r), a European mistletoe
      extract.
AB  - Evidence suggests that mistletoe extract has the potential to be used as an
      anticancer agent. Abnobaviscum F(r) is a European mistletoe extract from the host
      tree Fraxinus. We investigated the effect of Abnobaviscum F on the growth and
      survival of different leukemia cell lines. Abnobaviscum F treatment strongly
      reduced survival and induced apoptosis of K562 (human myeloid leukemia), RPMI
      8226 (human plasmacytoma) and L1210 (murine lymphocytic leukemia) cells in
      culture. Using K562 cells to further investigate the mechanism of action of
      Abnobaviscum F, we showed that Abnobaviscum F-induced cell death was associated
      with the activation of caspase-9, JNK-1/2 and p38 MAPK, as well as with the
      downregulation of Mcl-1, and inhibition of ERK-1/2 and PKB phosphorylation.
      Moreover, Abnobaviscum F treatment led to both a reduction of cellular
      glutathione (GSH) and the induction of ER stress (GRP78 and CHOP induction and
      eIF-2alpha phosphorylation). By contrast, Abnobaviscum F did not impact the
      expression of the DR4 and DR5 death receptors. The Abnobaviscum F-induced
      apoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmk or
      SP600125. Our results, therefore, show that Abnobaviscum F induces apoptosis of
      K562 cells through the activation of the intrinsic caspase pathway, the
      phosphorylation of JNK-1, the reduction of cellular GSH, and the induction of ER
      stress.

PMID- 22972374
TI  - On the use of capillary cytometry for assessing the bactericidal effect of TiO2.
      Identification and involvement of reactive oxygen species.
AB  - The photocatalytic antimicrobial properties of TiO2 were studied on
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacterial
      strains taken as model strains for pathogenic species mainly implied in
      nosocomial infections. Capillary cytometry, coupled to a double-staining method
      for visualizing membrane integrity as a cell viability indicator, was highlighted
      as a rapid, easy-to-use, and automated numeration technique for quantitative and
      reproducible determination of cellular viability and thus, was able to give an
      accurate evaluation of the bactericidal effect of UV-A photocatalysis. Cytometry
      also enabled the study of TiO2-bacteria interactions and aggregation in the dark
      as well as TiO2 cytotoxicity. Compared with the traditional agar plate
      cultivation method, a significatively weaker reduction in cell viability was
      recorded by cytometry whatever the bacteria, TiO2 concentration, and duration of
      the photocatalytic treatment. The mismatch between both numeration methods was
      attributed to: (i) the presence of mixed bacteria-TiO2 aggregates that could
      interfere with bacteria measurement on plates, (ii) prolonged contact of the
      bacteria with TiO2 during incubation, which could cause additional cytotoxic
      damage to the bacterial wall, and (iii) the counting of viable but non-culturable
      bacteria as live bacteria in cytometry, whereas they cannot grow on solid media.
      A more pronounced difference was observed for P. aeruginosa and S. aureus
      bacteria, for which 2.9 and 1.9 log10 survival reduction overestimations were
      measured by plate counting, respectively. Using chemiluminescence, full
      restoration of cell viability by controlled addition of the O2(-) scavenger
      superoxide dismutase enzyme suggests that O2(-) acts, in our conditions, as the
      main reactive oxygen species responsible for the photocatalytic attack towards
      the targeted bacteria.

PMID- 22972375
TI  - Biochemical and histological changes in the liver tissue of rainbow trout
      (Oncorhynchus mykiss) exposed to sub-lethal concentrations of diazinon.
AB  - The organophosphate insecticide diazinon is widely used to control pest in Iran.
      The purpose of the present study was to investigate the antioxidant and
      histopathological changes in the liver tissue of rainbow trout (Oncorhynchus
      mykiss) exposed to 0.1 and 0.2 mg/L of a commercial formula of diazinon for a
      period of 28 days. Antioxidant enzyme activities--catalase, superoxide dismutase,
      glutathione peroxidase and glutathione reductase--were determined after 7, 14 and
      28 days of exposure. Histopathological analyses were performed at the 28th day.
      All antioxidant enzymes were induced after 7 days of diazinon treatment in both
      concentrations of diazinon. Catalase and superoxide dismutase maintained elevated
      activities during all the treatment period. Glutathione peroxidase activity
      returned to the control values at the 14th day, decreasing to values below
      control at the 28th day in both diazinon concentrations. Glutathione reductase
      maintained increased activities at the 14th day in the 0.1 mg/L diazinon,
      decreasing to control values at the 28th day. In the 0.2 mg/L group, the activity
      returned to control values at the 14th and decreased below the control at the
      28th day. Total antioxidant capacity of hepatocytes significantly decreased in
      fishes exposed to diazinon during all experimental periods. Hypertrophy of
      hepatocytes, vacuolization of cell cytoplasm and hepatocyte cloudy swelling were
      observed in the liver tissue of fish exposed to both concentrations of diazinon.
      The results showed that diazinon altered the activity of antioxidant enzymes and
      the cellular total antioxidant capacity inducing oxidative stress and cellular
      damage in hepatocytes evidenced by histopathological analysis.

PMID- 22972377
TI  - Platelet response to aspirin in Chinese stroke patients is independent of genetic
      polymorphisms of COX-1 C50T and COX-2 G765C.
AB  - AIM: Aspirin resistance (AR) is common in Chinese stroke patients taking
      antiplatelet medications; however, few studies have documented the role of
      cyclooxygenase (COX)-1 C50T and COX-2 G765C polymorphisms in AR. The aim of this
      study was to investigate the prevalence of AR in Chinese stroke patients and the
      relationships between AR and COX-1 C50T and COX-2 G765C polymorphisms, and to
      evaluate the effect of these polymorphisms on platelet response to aspirin.
      METHODS: We prospectively enrolled 634 Chinese stroke patients. Platelet
      aggregation testing was performed before and after aspirin administration. The
      pre- and post-aspirin levels of 11-dehydrothromboxane B(2) (11-dTxB(2)) were
      determined in urine samples. COX-1 C50T and COX-2 G765C genotypes were determined
      by a polymerase chain reaction-allelic restriction assay. RESULTS: AR was
      detected in 129 patients (20.4%), aspirin semi-resistance (ASR) was detected in
      28 patients (4.4%), and aspirin sensitivity (AS) was detected in 477 patients
      (75.2%). There was no association between COX-1 C50T or COX-2 G765C polymorphisms
      and ASR+AR. Aspirin could efficiently reduce 11-dTxB(2) production by
      approximately 75%. In addition, platelet aggregation, both in response to
      arachidonic acid (AA) and adenosine 5'-diphosphate (ADP), was inhibited by more
      than 80% and 40%, respectively; however, the percentage reduction in platelet
      aggregation and 11-dTxB(2) levels was not significantly different between the COX
      1 C50T and COX-2 G765C genotypes (p>0.05). CONCLUSIONS: There was no association
      between COX-1 C50T and COX-2 G765C polymorphisms and AR in Chinese stroke
      patients. In addition, COX-1 C50T and COX-2 G765C polymorphisms had no effect on
      the platelet response to aspirin.

PMID- 22972376
TI  - AIF-mediated caspase-independent necroptosis requires ATM and DNA-PK-induced
      histone H2AX Ser139 phosphorylation.
AB  - The alkylating DNA-damage agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      induces a form of caspase-independent necroptosis implicating the mitochondrial
      flavoprotein apoptosis-inducing factor (AIF). Following the activation of PARP-1
      (poly(ADP-ribose) polymerase-1), calpains, BID (BH3 interacting domain death
      agonist), and BAX (Bcl-2-associated X protein), the apoptogenic form of AIF
      (tAIF) is translocated to the nucleus where, associated with Ser139
      phosphorylated histone H2AX (gammaH2AX), it creates a DNA-degrading complex that
      provokes chromatinolysis and cell death by necroptosis. The generation of
      gammaH2AX is crucial for this form of cell death, as mutation of H2AX Ser139 to
      Ala or genetic ablation of H2AX abolish both chromatinolysis and necroptosis. On
      the contrary, reintroduction of H2AX-wt or the phosphomimetic H2AX mutant (H2AX
      S139E) into H2AX(-/-) cells resensitizes to MNNG-triggered necroptosis. Employing
      a pharmacological approach and gene knockout cells, we also demonstrate in this
      paper that the phosphatidylinositol-3-OH kinase-related kinases (PIKKs) ATM
      (ataxia telangiectasia mutated) and DNA-dependent protein kinase (DNA-PK) mediate
      gammaH2AX generation and, consequently, MNNG-induced necroptosis. By contrast,
      H2AX phosphorylation is not regulated by ATR or other H2AX-related kinases, such
      as JNK. Interestingly, ATM and DNA-PK phosphorylate H2AX at Ser139 in a
      synergistic manner with different kinetics of activation. Early after MNNG
      treatment, ATM generates gammaH2AX. Further, DNA-PK contributes to H2AX Ser139
      phosphorylation. In revealing the pivotal role of PIKKs in MNNG-induced cell
      death, our data uncover a milestone in the mechanisms regulating AIF-mediated
      caspase-independent necroptosis.

PMID- 22972378
TI  - A cross-cultural perspective on psychological determinants of chronic fatigue
      syndrome: a comparison between a Portuguese and a Dutch patient sample.
AB  - BACKGROUND: Few studies focus on cross-cultural differences in Chronic fatigue
      syndrome (CFS). PURPOSE: This study aimed to (1) compare fatigue severity and
      impairment, somatic complaints, psychological distress, and quality of life (QoL)
      in a population of Portuguese and Dutch patients; (2) explore the differential
      contribution of behavioral and cognitive determinants of fatigue severity; and
      (3) investigate the relation between fatigue severity and somatic complaints on
      one hand and QoL on the other in both populations. METHOD: Eighty-five female
      patients from Portugal (Mean age = 47.54) and 167 female CFS patients from The
      Netherlands (Mean age = 44.93) participated in the study. All participants were
      surveyed for demographic and clinical characteristics, fatigue severity, somatic
      symptoms, psychological distress, (physical and psychological) QoL, physical
      activity, behavior regulation patterns, and illness representations. RESULTS:
      Cross-cultural differences were found in relation to working status, duration of
      fatigue symptoms, psychological distress, somatic complaints, and psychological
      QoL. Although behavioral characteristics and illness representations were
      significantly associated with fatigue severity in both Portuguese and Dutch
      patients, there were important differences in the determinants of CFS. Moreover,
      higher levels of fatigue and severity of other somatic complaints were related to
      poor QoL. CONCLUSIONS: These findings show cross-cultural similarities and
      differences in clinical characteristics and psychological determinants of CFS
      that are important in view of diagnosis and treatment.

PMID- 22972379
TI  - Using passive air samplers to assess local sources versus long range atmospheric
      transport of POPs.
AB  - Passive air samplers (PAS) are cost-efficient tools suitable for spatial mapping
      of atmospheric concentrations of persistent organic pollutants (POPs). The
      objective of this study was to use PAS to (i) determine atmospheric
      concentrations of selected POPs in Norwegian coastal zones with consumption
      advisories on seafood (N = 22), and (ii) evaluate a simple nested monitoring
      approach to assess the relative influence of local vs. long-range atmospheric
      transport (LRAT) at coastal sites. The latter was facilitated by comparison with
      data from a coordinated European-wide campaign in which an identical sampling and
      analytical approach was followed. Air concentrations were calculated based on the
      loss of performance reference compounds (PRCs), and results are presented for
      selected polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons
      (PAHs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB),
      dichlorodiphenyltrichloroethanes (DDTs) and chlordanes. Air concentrations of
      PCBs were generally highest at sites within larger cities and up to about an
      order of magnitude higher than anticipated on the basis of LRAT alone. The
      distribution of PAHs and HCB occasionally showed elevated concentrations at
      coastal sites with ongoing or former industrial activity, while an urban site was
      significantly influenced by banned insecticides (technical DDT and lindane).
      Coastal sites were also elevated in alpha-HCH beyond the anticipated LRAT
      contribution, which we attribute to volatilization from the sea. We conclude that
      a simple nested PAS monitoring approach provides useful information for screening
      efforts aiming to assess both atmospheric burdens as well as the relative
      significance of local sources in controlling these burdens at sites in
      contaminated areas.

PMID- 22972380
TI  - Investigation of genetic risk factors for chronic adult diseases for association
      with preterm birth.
AB  - Preterm birth (PTB) is the leading cause of infant mortality. PTB pathophysiology
      overlaps with those of adult cardiovascular, immune and metabolic disorders
      (CIMD), with mechanisms including inflammation, immunotolerance, thrombosis, and
      nutrient metabolism. Whereas many genetic factors for CIMD have been identified,
      progress in PTB has lagged. We hypothesized that highly validated genetic risk
      factors for CIMD may also be associated with PTB. We conducted case-control study
      of four female cohorts with spontaneous PTB (n = 673) versus term (n = 1119). Of
      35 SNPs genotyped, there were 13 statistically significant associations (P <
      0.05), which were more than expected (binomial test; P = 0.02). In US White (307
      cases/342 controls), the G allele of HLA-DQA1 (A/G) rs9272346 was protective for
      PTB in the initial discovery cohort (P = 0.02; OR = 0.65; 95 % CI 0.46, 0.94).
      This protective association replicated (P = 0.02; OR = 0.85; 95 % CI 0.75, 0.97)
      nominally in the Danish Cohort (883 cases, 959 controls), but lost significance
      upon multiple testing correction. We observed more statistically significant
      associations than expected, suggesting that chance is an unlikely explanation for
      one or more of the associations. Particularly, a protective association of the G
      allele of HLA-DQA1 was found in two independent cohorts, and in previous studies,
      this same allele was found to protect against type-1-diabetes (meta-analysis P
      value 5.52 * 10(-219)). Previous investigations have implicated HLA phenotypic
      variation in recurrent fetal loss and in chronic chorioamnionitis. Given the
      limited sample size in his study, we suggest larger studies to further
      investigate possible HLA genetic involvement in PTB.

PMID- 22972381
TI  - Phenotypic analysis of Salmonella enterica serovar Typhimurium rpoE mutants
      encoding RNA polymerase extracytoplasmic stress response sigma factors sigma(E)
      with altered promoter specificity.
AB  - We previously identified mutants in the rpoE gene of Salmonella enterica serovar
      Typhimurium (S. Typhimurium) encoding RNA polymerase extracytoplasmic stress
      response sigma factors sigma(E) with altered promoter specificity. The
      replacement of the conserved R171 residue in the conserved region 4.2 of sigma(E)
      by different amino acid residues exhibited different phenotypes. While R171A
      almost completely abolished sigma factor activity, R171G and R171C mutant changes
      imparted a relaxed recognition phenotype to the sigma factor. In the present
      study, we introduced these mutations into the S. Typhimurium chromosome to
      investigate their phenotype during ethanol stress and in promoter recognition.
      Both relaxed sigma factors were found to initiate transcription from a high
      number of artificial promoters in the S. Typhimurium genome. Both mutants had
      substantially decreased activity under stress conditions. However, this decreased
      activity and also the recognition of atypical promoters had no significant effect
      upon growth, even in stressful conditions.

PMID- 22972382
TI  - Brominated flame retardants stimulate mouse immune cells in vitro.
AB  - Brominated flame retardants (BFRs) are widely used in consumer products. Their
      toxicological effects as endocrine disruptors have been partly examined. However,
      their immunological effects have not been elucidated. To evaluate the effects of
      BFRs on immune responses, we investigated whether BFRs affect phenotypes and the
      function of immune cells in vitro. Here we examined the commercial
      pentabromodiphenyl ether mixture (DE-71), octabromodiphenyl ether mixture (DE
      79), decabromodiphenyl ether mixture (DE-83R), hexabromocyclododecane (HBCD) and
      tetrabromobisphenol A (TBBPA). Splenocytes and bone marrow (BM) cells were
      prepared from atopic prone NC/Nga mice. Splenocytes were exposed to each BFR for
      24 h. BM cells were cultured with granulocyte macrophage-colony stimulating
      factor (GM-CSF) for 8 days and BM-derived dendritic cells (BMDCs) were exposed to
      each BFR for 24 h. In another experiment, BM cells were cultured with GM-CSF in
      the presence of each BFR for 6 days during BMDC differentiation. After exposure,
      cell surface molecule expression and cytokine production were investigated. Each
      BFR increased MHC class II and CD86 expression and interleukin (IL)-4 production
      in splenocytes. DE-71, HBCD and TBBPA increased T cell receptor (TCR) expression
      in splenocytes. In both experiments, all BFRs except TBBPA increased DEC205
      expression in BMDCs. BMDCs that differentiated in the presence of HBCD showed
      enhanced MHC class II, CD80, CD86 and CD11c expression. The results demonstrate
      that some BFRs may stimulate immune cells. BFRs can induce or enhance
      immune/allergic responses by increasing antigen presentation-related molecule
      expression and IL-4 production.

PMID- 22972383
TI  - Clinical pharmacist's contribution to medication reconciliation on admission to
      hospital in Ireland.
AB  - BACKGROUND: Medication reconciliation has been mandated by the Irish government
      at transfer of care. Research is needed to determine the contribution of clinical
      pharmacists to the process. OBJECTIVE: To describe the contribution of emergency
      department based clinical pharmacists to admission medication reconciliation in
      Ireland. MAIN OUTCOME MEASURE: Frequency of clinical pharmacist's activities.
      SETTING: Two public university teaching hospitals. METHODOLOGY: Adults admitted
      via the accident and emergency department, from a non-acute setting, reporting
      the use of at least three regular prescription medications, were eligible for
      inclusion. Medication reconciliation was provided by clinical pharmacists to
      randomly-selected patients within 24-hours of admission. This process includes
      collecting a gold-standard pre-admission medication list, checking this against
      the admission prescription and communicating any changes. A discrepancy was
      defined as any difference between the gold-standard pre-admission medication list
      and the admission prescription. Discrepancies were communicated to the clinician
      in the patient's healthcare record. Potentially harmful discrepancies were also
      communicated verbally. Pharmacist activities and unintentional discrepancies,
      both resolved and unresolved at 48-hours were measured. Unresolved discrepancies
      were confirmed verbally by the team as intentional or unintentional. A reliable
      and validated tool was used to assess clinical significance by medical
      consultants, clinical pharmacists, community pharmacists and general
      practitioners. RESULTS: In total, 134 patients, involving 1,556 medications, were
      included in the survey. Over 97 % of patients (involving 59 % of medications)
      experienced a medication change on admission. Over 90 % of patients (involving 29
      % of medications) warranted clinical pharmacy input to determine whether such
      changes were intentional or unintentional. There were 447 interventions by the
      clinical pharmacist regarding apparently unintentional discrepancies, a mean of
      3.3 per patient. In total, 227 (50 %) interventions were accepted and
      discrepancies resolved. At 48-hours under half (46 %) of patients remained
      affected by an unintentional unresolved discrepancy (60 % related to omissions).
      Verbally communicated discrepancies were more likely to be resolved than those
      not communicated verbally (Chi-square (1) = 30.029 p < 0.05). Under half of
      unintentional unresolved discrepancies (46 %) had the potential to cause minor
      harm compared to 70 % of the resolved unintentional discrepancies. None had the
      potential to result in severe harm. CONCLUSION: Clinical pharmacists contribute
      positively to admission medication reconciliation and should be engaged to
      deliver this service in Ireland.

PMID- 22972384
TI  - From Tyrian purple to kinase modulators: naturally halogenated indirubins and
      synthetic analogues.
AB  - Indirubins represent a small category of compounds with significant
      pharmacological activity focusing on the inhibition of protein kinases. A series
      of derivatives has been developed during the last 15 years aiming the
      investigation and amelioration of the indirubin scaffold in terms of activity,
      selectivity, and drug-likeness. The current article focuses on the naturally
      brominated indirubins present in the famous historic dye of Tyrian purple,
      attempting to gather all available literature regarding biosynthesis, isolation,
      and synthesis of related analogues. Halogenated indirubins are by far one of the
      most important subcategories of indirubins, with its main representatives 6
      bromoindirubin (6BI) and 6-bromoindirubin-3'-oxime (6BIO) possessing an increased
      selectivity against GSK-3. This review attempts to summarize concisely
      structure/activity relationships among closely related halogenated analogues in
      terms of protein kinase inhibition and selectivity, while it also focuses on the
      various biological applications arising from the interactions of halogenated
      indirubins with molecular targets. Those include effects of halogenated
      indirubins on stem cells, cardiac, renal, and pancreatic cells, on leukemia and
      solid tumors, and on neurodegeneration.

PMID- 22972385
TI  - Identification of chemotaxis sensory proteins for amino acids in Pseudomonas
      fluorescens Pf0-1 and their involvement in chemotaxis to tomato root exudate and
      root colonization.
AB  - Pseudomonas fluorescens Pf0-1 showed positive chemotactic responses toward 20
      commonly-occurring l-amino acids. Genomic analysis revealed that P. fluorescens
      Pf0-1 possesses three genes (Pfl01_0124, Pfl01_0354, and Pfl01_4431) homologous
      to the Pseudomonas aeruginosa PAO1 pctA gene, which has been identified as a
      chemotaxis sensory protein for amino acids. When Pf01_4431, Pfl01_0124, and
      Pfl01_0354 were introduced into the pctA pctB pctC triple mutant of P. aeruginosa
      PAO1, a mutant defective in chemotaxis to amino acids, its transformants showed
      chemotactic responses to 18, 16, and one amino acid, respectively. This result
      suggests that Pf01_4431, Pfl01_0124, and Pfl01_0354 are chemotaxis sensory
      proteins for amino acids and their genes were designated ctaA, ctaB, and ctaC,
      respectively. The ctaA ctaB ctaC triple mutant of P. fluorescens Pf0-1 showed
      only weak responses to Cys and Pro but no responses to the other 18 amino acids,
      indicating that CtaA, CtaB, and CtaC are major chemotaxis sensory proteins in P.
      fluorescens Pf0-1. Tomato root colonization by P. fluorescens strains was
      analyzed by gnotobiotic competitive root colonization assay. It was found that
      ctaA ctaB ctaC mutant was less competitive than the wild-type strain, suggesting
      that chemotaxis to amino acids, major components of root exudate, has an
      important role in root colonization by P. fluorescens Pf0-1. The ctaA ctaB ctaC
      triple mutant was more competitive than the cheA mutant of P. fluorescens Pf0-1,
      which is non-chemotactic, but motile. This result suggests that chemoattractants
      other than amino acids are also involved in root colonization by P. fluorescens
      Pf0-1.

PMID- 22972386
TI  - Ammonia-oxidizing bacteria rather than ammonia-oxidizing archaea were widely
      distributed in animal manure composts from field-scale facilities.
AB  - The distribution of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in cattle,
      swine, and chicken manure compost was analyzed. PCR-denaturing gradient gel
      electrophoresis (DGGE) showed that a Candidatus Nitrososphaera gargensis-like
      sequence dominated in cattle manure compost, while few AOA were detected in other
      composts. In the case of AOB, Nitrosomonas-like sequences were detected with
      higher diversity in cattle and swine manure composts. The relative abundance of
      ammonia oxidizers by real-time PCR revealed that more AOB was present in compost
      except in one swine manure compost. Our results indicated that AOB rather than
      AOA are widely distributed in animal manure compost.

PMID- 22972389
TI  - Interaction between a bisphosphonate, tiludronate and nanocrystalline apatite: in
      vitro viability and proliferation of HOP and HBMSC cells.
AB  - Nanocrystalline apatites (NCA) are the inorganic components of mineralized
      tissues and they have been recently proposed as biomaterials for drug delivery
      systems. Bisphosphonates (BPs) are currently the reference drugs used to treat
      diseases involving bone disorders such as osteoporosis. Nevertheless, the
      interaction phenomena between BP molecules and apatite nanocrystals of bone are
      not well understood. Therefore, the adsorption characteristics have been examined
      and cellular activity of tiludronate molecules on NCA as models of bone mineral
      has been investigated. Adsorption experiments of tiludronate onto NCA were
      carried out and revealed a Langmuir-type adsorption isotherm. The uptake of
      tiludronate molecules is associated with a release of phosphate ions, indicating
      that the main reaction is an ion exchange process involving surface anions. The
      results evidence the strong affinity of BP molecules for the apatitic surface.
      The interactions of NCA-tiludronate associations with human osteoprogenitor cells
      and human bone marrow stromal cells do not reveal any cytotoxicity and evidence
      the activity of adsorbed tiludronate molecules. Moreover, an evolution of the
      physico-chemical characteristics of the apatitic substrate during biological
      study was observed, highlighting the existence of dynamic interactions. This work
      contributes to clarifying the reaction mechanisms between BPs and biomimetic
      apatites.

PMID- 22972388
TI  - Multidrug-resistance and toxic metal tolerance of medically important bacteria
      isolated from an aquaculture system.
AB  - The use of antimicrobials and toxic metals should be considered carefully in
      aquaculture and surrounding environments. We aimed to evaluate medically relevant
      bacteria in an aquaculture system and their susceptibility to antimicrobials and
      toxic metals. Selective cultures for enterobacteria (ENT), non-fermenting Gram
      negative rods (NFR) and Gram-positive cocci (GPC) were obtained from water
      samples collected in two different year seasons. The isolated bacteria were
      biochemically identified and antimicrobial and toxic metal susceptibility
      patterns were determined. Overall, 407 representative strains were recovered. In
      general, bacteria isolated from fish ponds showed higher multiple antibiotic
      resistance indices when compared to those isolated from a water-fed canal.
      Resistance to penicillin and azithromycin was observed more frequently in the GPC
      group, whereas resistance to ampicillin and ampicillin/sulbactam or gentamicin
      was observed more frequently in the ENT and NFR groups, respectively. All the
      isolated bacteria were tolerant to nickel, zinc, chromium and copper at high
      levels (>=1,024 MUg mL(-1)), whereas tolerance to cadmium and mercury varied
      among the isolated bacteria (2-1,024 MUg mL(-1)). Multidrug-resistant bacteria
      were more frequent and diverse in fish ponds than in the water-fed canal. A
      positive correlation was observed between antimicrobial resistance and metal
      tolerance. The data point out the need for water treatment associated with the
      aquaculture system.

PMID- 22972387
TI  - Identification of active denitrifiers in rice paddy soil by DNA- and RNA-based
      analyses.
AB  - Denitrification occurs markedly in rice paddy fields; however, few microbes that
      are actively involved in denitrification in these environments have been
      identified. In this study, we used a laboratory soil microcosm system in which
      denitrification activity was enhanced. DNA and RNA were extracted from soil at
      six time points after enhancing denitrification activity, and quantitative PCR
      and clone library analyses were performed targeting the 16S rRNA gene and
      denitrification functional genes (nirS, nirK and nosZ) to clarify which microbes
      are actively involved in denitrification in rice paddy soil. Based on the
      quantitative PCR results, transcription levels of the functional genes agreed
      with the denitrification activity, although gene abundance did not change at the
      DNA level. Diverse denitrifiers were detected in clone library analysis, but
      comparative analysis suggested that only some of the putative denitrifiers,
      especially those belonging to the orders Neisseriales, Rhodocyclales and
      Burkholderiales, were actively involved in denitrification in rice paddy soil.

PMID- 22972390
TI  - Metal chelates anchored to poly-L-peptides and linear D,L-alpha-peptides with
      promising nanotechnological applications.
AB  - Regular configurationally alternating amino acid sequences generate cyclic and
      linear helical peptides with a local beta-conformation able to self-assemble in
      nanowires and nanoscaffolds directed and stabilized by hydrogen bonds. The
      possibility of modulating the chemical profile of the various amino acid residues
      containing reactive side chains means that peptides could be flexible templates
      for creating various building blocks. A method for the design of molecules with
      potential spintronic properties is described. Peptides containing lysine
      residues, the side chains of which are bridged through the formation of metal
      chelates via Schiff bases, could provide stable molecular channels. When metal
      chelates with high electron spin states are used, their coupling could generate
      materials that are interesting due to their magnetic properties as well as for
      the patterning of nanometric lattices driven by their orientation under a
      magnetic field. With this aim, three alternating D- and L-lysine-containing
      octapeptides are synthesized and the formation of their bis(pyridoxalaldimine)
      copper(II) chelate derivatives is shown by absorption and circular dichroism
      spectroscopies.

PMID- 22972392
TI  - Changing paradigms in spondylarthritis: the myofibroblast signature.

PMID- 22972391
TI  - Transient receptor potentials (TRPs) and anaphylaxis.
AB  - The transient receptor potential (TRP) superfamily consists of 28 members in
      mammals (27 in human) that act as polymodal sensors and ion channels. They
      regulate cellular calcium influx, generate depolarization thereby triggering
      voltage dependent cellular processes, and in turn they are critical in inducing
      the metabolic activities of cells. It is increasingly apparent that many of the
      inflammatory mediators released in allergic reactions involve at least two of
      these ion channels, the 'Vanilloid' TRPV1 and the 'Ankyrin" TRPA1. This review
      mainly focuses on TRPV1 and TRPA1 and the role they have in the allergic response
      and how these receptors may be influenced in exercise-induced anaphylaxis. The
      threshold to react to an allergen for mast cells and lymphocytes can be reduced
      by activating the melastatin channel TRPM4. This channel is briefly discussed in
      the context of allergy.

PMID- 22972393
TI  - Effect of autologous platelet-rich plasma on persistent corneal epithelial defect
      after infectious keratitis.
AB  - PURPOSE: Platelet-rich plasma (PRP) harbors high concentrations of growth factors
      related to the promotion of wound healing. We evaluated the efficacy of PRP
      eyedrops in the treatment of persistent epithelial defects (PEDs). METHODS:
      Autologous PRP and autologous serum (AS) were prepared from whole blood. The
      concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, epidermal
      growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed
      and compared. The corneal epithelial healing efficacy of PRP was compared with
      that of AS in patients with PED induced by post-infectious inflammation. RESULTS:
      The concentrations of TGF-beta1, TGF-beta2, EGF, vitamin A and fibronectin in the
      PRP and AS were not statistically different. However, the concentrations of EGF
      in the PRP were significantly greater than in the AS. AS was used in 17 and PRP
      in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP
      treated eyes were significantly higher than those treated with AS. CONCLUSIONS:
      The PRP was effective in the treatment of PEDs. This may be attributable to its
      high concentration of platelet-contained growth factors, most notably EGF. PRP
      could be an effective, novel treatment option for chronic ocular surface disease.

PMID- 22972394
TI  - Hong's grading for evaluating anterior chamber angle width.
AB  - PURPOSE: To compare Hong's grading method with anterior segment optical coherence
      tomography (AS-OCT), gonioscopy, and the dark-room prone-position test (DRPT) for
      evaluating anterior chamber width. METHODS: The anterior chamber angle was graded
      using Hong's grading method, and Hong's angle width was calculated from the
      arctangent of Hong's grades. The correlation between Hong's angle width and AS
      OCT parameters was analyzed. The area under the receiver operating characteristic
      curve (AUC) for Hong's grading method when discriminating between narrow and open
      angles as determined by gonioscopy was calculated. Correlation analysis was
      performed between Hong's angle width and intraocular pressure (IOP) changes
      determined by DRPT. RESULTS: A total of 60 subjects were enrolled. Of these
      subjects, 53.5 % had a narrow angle. Hong's angle width correlated significantly
      with the AS-OCT parameters (r = 0.562-0.719, P < 0.01). A Bland-Altman plot
      showed relatively good agreement between Hong's angle width and the angle width
      obtained by AS-OCT. The ability of Hong's grading method to discriminate between
      open and narrow angles was good (AUC = 0.868, 95 % CI 0.756-0.942). A significant
      linear correlation was found between Hong's angle width and IOP change determined
      by DRPT (r = -0.761, P < 0.01). CONCLUSIONS: Hong's grading method is useful for
      detecting narrow angles. Hong's grading correlated well with AS-OCT parameters
      and DRPT.

PMID- 22972395
TI  - A novel cell therapy for stress urinary incontinence, short-term outcome.
AB  - AIMS: The aim of this study was the safety assessment of urethra injections of
      autologous total nucleated cells (TNCs) along with platelets, which focused on
      the outcome over a 6 month period. METHODS: An open, prospective study was
      conducted on 9 patients with severe stress urinary incontinence (SUI). At the
      baseline, 1, 3, and 6 months after external urethral sphincteric and submucosal
      injections of autologous TNCs along with platelets, the patients were assessed
      according to cough tests, Q-Tip tests, urodynamics, 1 hr pad tests, upper tract
      ultrasonography (UTU), post voiding residue (PVR), International Consultation on
      Incontinence Questionnaire-Urinary incontinence (ICIQ-UI), and International
      Consultation on Incontinence Modular Questionnaire-Quality of Life (ICIQ-QOL). On
      the 3rd month post-injection, the maximum urethral closure pressure (MUCP) and
      abdominal leak point pressure (ALPP) were measured in one patient with intrinsic
      sphincteric deficiency (ISD; the baseline: ALPP < 60 and MUCP < 30 cmH(2)O).
      RESULTS: No complications were observed after injection. At 6-months' follow up
      (F/U), all the patients considered themselves clinically cured with eight women
      completely continent and one marked improvement. Mean age was 48.9 +/- 13.8
      years. Before the injection, urodynamics, UTU, and PVR were normal and cough
      tests, 1 hr pad tests were positive in patients. At 1, 3, and 6 months post
      injection, there was a significant improvement in ICIQ-UI, ICIQ-QOL (P < 0.05).
      UTU and PVR were normal, cough tests, and 1 hr pad tests were negative, except
      for ISD patient with severe coughs (at month 3: ALPP = 92 and MUCP > 30 cmH(2)O).
      CONCLUSION: Cell therapy consisting of intrasphincteric and submucosal injections
      of autologous TNCs along with platelets in SUI patients is a feasible and safe
      procedure. The results point out those subjects cured or with marked improvement
      after 6 months F/U.

PMID- 22972396
TI  - Luminescent neutral platinum complexes bearing an asymmetric N(^) N(^) N ligand
      for high-performance solution-processed OLEDs.
AB  - The synthesis and full characterization of new platinum complexes bearing a bulky
      asymmetric dianionic tridentate ligand is reported. The hindrance of the ligand
      prevents detrimental intermolecular interactions yielding to highly emitting
      species in both crystalline state and thin-film. Such properties prompted their
      successful use in solution-processed OLEDs, showing remarkable external quantum
      efficiency up to 5.6%.

PMID- 22972399
TI  - Effect of low-and high-dose atorvastatin on carotid artery distensibility using
      carotid magnetic resonance imaging -a post-hoc sub group analysis of ATHEROMA
      (Atorvastatin Therapy: Effects On Reduction Of Macrophage Activity) Study.
AB  - AIM: To assess the effect of low-(10 mg) or high-(80 mg) dose atorvastatin on
      carotid artery distensibility in patients with asymptomatic carotid artery
      disease using carotid magnetic resonance imaging. METHODS: Eighteen patients
      underwent initial 2-dimensional ECG gated-phase contrast carotid MR imaging and
      off-line applanation tonometry for distensibility assessment before randomisation
      to receive low- or high-dose statins and this was repeated at 12 weeks. Phase and
      magnitude images from the 2-D phase contrast acquisitions were used for
      quantification of distensibility and compliance coefficients and were compared
      between the low- and high-dose statin groups. RESULTS: Both groups were
      comparable with regards to their demographics, co-morbidities and baseline
      cholesterol levels. After 12 weeks of high-dose statin administration, a
      significant decrease in LDL (p=0.003) and CRP (p=0.03) was observed. At 12 weeks,
      the distensibility coefficient of the common and internal carotid artery was
      found to be significantly higher (with respect to baseline) in the high-dose
      group (p=0.004 and p=0.007, respectively). The compliance coefficient was
      likewise found to be raised in the high-dose group when compared with the low
      dose group [common carotid (p=0.002), internal carotid (p=0.009)]. CONCLUSIONS:
      High-dose atorvastatin tends to reduce carotid arterial stiffness, as suggested
      by increased distensibility and compliance coefficients; however, these results
      need validation through large-scale trials to fully establish their possible use
      in clinical practice.

PMID- 22972397
TI  - SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells.
AB  - Unlike activated CD4(+) T cells, resting CD4(+) T cells are highly resistant to
      productive HIV-1 infection. Early after HIV-1 entry, a major block limits reverse
      transcription of incoming viral genomes. Here we show that the deoxynucleoside
      triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1
      RNA in resting CD4(+) T cells. SAMHD1 is abundantly expressed in resting CD4(+) T
      cells circulating in peripheral blood and residing in lymphoid organs. The early
      restriction to infection in unstimulated CD4(+) T cells is overcome by HIV-1 or
      HIV-2 virions into which viral Vpx is artificially or naturally packaged,
      respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated
      proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide
      pools precede successful infection by Vpx-carrying HIV. Resting CD4(+) T cells
      from healthy donors following SAMHD1 silencing or from a patient with Aicardi
      Goutieres syndrome homozygous for a nonsense mutation in SAMHD1 were permissive
      for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1
      infection in the large pool of noncycling CD4(+) T cells in vivo. Bypassing
      SAMHD1 was insufficient for the release of viral progeny, implicating other
      barriers at later stages of HIV replication. Together, these findings may unveil
      new ways to interfere with the immune evasion and T cell immunopathology of
      pandemic HIV-1.

PMID- 22972400
TI  - Surgical resection of pediatric skull base meningiomas.
AB  - PURPOSE: Meningiomas in children are rare, especially those located at the skull
      base. In this study, we report our experience of meningioma surgery in the
      pediatric population and compare our findings of skull base (SB) versus non-skull
      base (NSB) meningiomas. METHODS: From our database of 724 surgically treated
      meningioma patients at the University Hospital, Zurich between 1995 and 2010, 12
      patients under 18 years of age were identified. Data for those patients was
      retrospectively collected through chart review. A descriptive comparison between
      SB and NSB meningiomas was undertaken to determine statistical significance.
      RESULTS: In all 12 children (seven males, five females; mean age 12.2 +/- 4.3
      years), surgical removal of the meningioma was performed microsurgically with a
      mean follow-up of 53 months (range 12-137 months). Of the 12 tumors, six were
      located in the SB and six in the NSB. Comparing SB to NSB lesions, the mean age
      was 11 +/- 3.8 versus 14 +/- 4.6 years, male/female gender distribution was 5:1
      compared to 1:5, mean tumor size was 7.5 +/- 6.2 versus 26 +/- 15.8 cm(2) (p =
      0.03), and mean surgery time was 347 versus 214 min. While WHO grade was similar
      for both groups, the Simpson grade revealed more extensive resection for NSB
      meningiomas. The Glasgow Outcome Scale at last follow-up was favorable for both
      groups. CONCLUSIONS: Meningioma surgery was safe with favorable outcomes. SB
      meningiomas were significantly smaller in size, were less likely to undergo
      complete resection, and had a predilection for younger, male patients.

PMID- 22972401
TI  - Mapping of the atomic lattice orientation of a graphite flake using macroscopic
      liquid crystal texture.
AB  - The electronic properties of graphene depend critically on its lattice
      orientation and edge type. However, it is very difficult to identify them, and
      they are accessible only using sophisticated tools. In this paper, we show an
      easy and reliable way to reveal the lattice orientation and edge type of graphene
      and graphite flakes, i.e. multi-layered graphene. Nematic liquid crystals have
      the potential to align themselves into three symmetric and equivalent
      orientations on crystalline graphite. The director of macroscopic texture due to
      the elasticity indicates the lattice orientation of the top graphite layer. By
      analyzing the director orientation using a polarizing optical microscope, we were
      able to show the lattice orientation, chiral angle and edge type of graphene and
      graphite flakes on the macroscopic scale. As liquid crystals are soft and easily
      removable, our technique has little chance of influencing the following processes
      for graphene manipulation.

PMID- 22972402
TI  - Antihyperlipidemic and antitumor effects of chickpea albumin hydrolysate.
AB  - This study was undertaken to determine the effects of chickpea albumin
      hydrolysate (CAH) on antihyperlipidemic and antitumor functions. The
      antihyperlipidemic results showed that CAH exhibited a dose dependent ability to
      decrease the levels of serum total cholesterol, triglyceride, LDL cholesterol
      (LDL-C), while increasing HDL cholesterol (HDL-C). Additionally, the appearance
      of the hyperlipidemic livers was ameliorated significantly. The antitumor results
      showed that CAH administration significantly increased the tumor inhibition rate
      and decreased tumor volume. CAH was also able to increase the spleen index and
      promote spleen lymphocyte proliferation. In addition, CAH treatment led to a
      remarkable rise in the superoxide dismutase (SOD) activity, while dramatically
      decreasing malondialdehyde (MDA) in the liver. Most importantly, we found that
      the physical conditions, such as appetite, activity, and coat luster of the mice
      in the CAH test group were better than those in the tumor control (TC) and
      positive control (PC) groups. These results taken together indicate that CAH
      warrants being further investigated and developed as an adjunctive element for
      hepatic lipid control, as well as antitumor and hypolipidemic therapies.

PMID- 22972403
TI  - Size dependent aqueous dispersibility of carboxylated multiwall carbon nanotubes.
AB  - The size dependent colloidal behavior of aqueous dispersions of carboxylated
      multiwall carbon nanotubes (c-MWCNTs) is presented. The presence of carboxylic
      groups provided electrostatic stabilization in water, where the size affected
      agglomeration. While aspect ratio did not show any definite correlation, the
      hydrophobicity indices (HI), zeta potential and aggregation kinetics showed
      dependence on the length of the c-MWCNTs where the shorter c-MWCNTs showed
      significantly lower HI values, smaller particle aggregates, higher zeta potential
      values and higher critical coagulation concentrations (ccc) in the presence of
      electrolytes. Although the diameter of the short c-MWCNTs did not appear to
      influence their aggregation behavior, the longer c-MWCNTs showed a dependence on
      diameter where stability decreased with increasing CNT diameter.

PMID- 22972404
TI  - Let-7a inhibits proliferation and induces apoptosis by targeting EZH2 in
      nasopharyngeal carcinoma cells.
AB  - Let-7a is frequently downregulated in various types of human cancer including
      nasopharyngeal carcinoma. However, the underlying mechanism of let-7a action in
      nasopharyngeal carcinoma remains elusive. In this study, we show that the
      enhancer of zeste homolog 2 (EZH2) is a direct target of let-7a in human
      nasopharyngeal carcinoma cells. The inhibition of EZH2 in vitro by let-7a, EZH2
      siRNA, attenuated nasopharyngeal carcinoma cell growth, inhibited cell
      proliferation and induced cell apoptosis. In addition, for each biological
      process we identified ontology-associated transcripts that significantly
      correlate with EZH2 expression. Finally, the expression of EZH2 significantly
      abrogated let-7a-mediated cell proliferation and apoptosis in the nasopharyngeal
      carcinoma cells. Taken together, our results suggest that let-7a and EZH2 may be
      potential therapeutic targets for nasopharyngeal carcinoma.

PMID- 22972407
TI  - Ventriculoperitoneal shunts in children on peritoneal dialysis: a survey of the
      International Pediatric Peritoneal Dialysis Network.
AB  - OBJECTIVE: The aim of this study was to inform best evidence-based practice by
      collating and disseminating the experiences of members of the International
      Pediatric Peritoneal Dialysis Network with children having concurrent
      ventriculoperitoneal shunts (VPS) and peritoneal dialysis catheters (PDC).
      METHODS: An online questionnaire was created and distributed to all 135 centers
      participating in the International Pediatric Peritoneal Dialysis Network; the
      overall response rate was 56 %. RESULTS: A total of 18 patients with a concurrent
      VPS and PDC were reported. The children were 0-12 (mean 6.8) years old at the
      time of placement of the second indwelling device (PDC or VPS). In 15 cases, the
      PDC was inserted post-VPS. On average, the two catheters were present
      concurrently for 23 (range 1-60) months. There were 20 episodes of peritonitis
      observed in 11 of the 18 patients during a period of 392 months at risk, which is
      a peritonitis rate of 1/19.6 months. Only one patient developed both a VPS
      infection and an episode of peritonitis, and these events were temporally
      unrelated. No episodes of an ascending shunt infection or meningitis occurred in
      association with any episode of peritonitis, and no other complications of
      catheter dysfunction were described. CONCLUSIONS: The rate of peritonitis, the
      absence of any documented ascending or descending infections and the lack of
      catheter dysfunction during the period of observation suggests that the presence
      of, or need for, a VPS should not preclude PD as a safe option for children
      requiring renal replacement therapy.

PMID- 22972408
TI  - [Risks for Burden among Relatives Caring for Schizophrenia Patients].
AB  - OBJECTIVE: Relatives of persons with schizophrenia have an essential role in
      informal caregiving. This may result in a high level of burden. Aim of the study
      was to investigate, if the frequency of unmet needs among relatives caring for
      schizophrenia patients increases the risk for burden among these relatives.
      METHODS: 135 relatives of patients with schizophrenia or schizoaffective disorder
      were investigated by means of the "Involvement Evaluation Questionnaire" (IEQ)
      and the "Carer's Needs Assessment for Schizophrenia" (CNA-S). RESULTS: Multiple
      linear regression analyses showed positive associations between the frequency of
      caregivers' unmet needs and the IEQ-subscores "tension" and "worrying". Further,
      the IEQ-subscore "worrying" was significantly lower among caregivers of
      outpatients than among caregivers of inpatients or day hospital patients. The IEQ
      subscore "urging" was significantly associated with patient's negative symptoms.
      CONCLUSION: Unmet needs among caring relatives have negative effects on their
      burden. Further, the patients' type of treatment setting (inpatient, outpatient,
      day hospital) seems to predict caregivers' burden.

PMID- 22972409
TI  - [Behavioural problems and personality change related to cerebral amyloid
      angiopathy].
AB  - OBJECTIVE: Cerebral amyloid angiopathy (CAA) belongs to the group of amyloidoses
      that are characterized by the deposition of insoluble and tissue-damaging amyloid
      proteins. Spontaneous intracerebral hemorrhage is the common clinical
      presentation of CAA resulting from the degenerative effect of beta amyloid on the
      cerebral vascular system. Though CAA is rather a neurological disease psychiatric
      symptoms can occur and even dominate the clinical picture. METHODS: A case report
      is presented in order to illustrate the association between CAA and psychiatric
      symptoms. RESULTS: We report the case of a 54-year-old female patient with
      radiologic references to a probable CAA and mild cognitive impairment who
      developed behavioural difficulties and personality change that necessitated a
      psychiatric treatment. Psychiatric symptoms were most likely due to CAA.
      CONCLUSIONS: CAA can be associated with psychiatric symptoms and hence should be
      considered in the treatment of elderly patients with behavioural problems or
      personality changes. Diagnostic neuroimaging and examination of cerebrospinal
      fluid is recommended.

PMID- 22972410
TI  - Disease-specific and inflammation-independent stromal alterations in
      spondylarthritis synovitis.
AB  - OBJECTIVE: The molecular processes driving the distinct patterns of synovial
      inflammation and tissue remodeling in spondylarthritis (SpA) as compared to
      rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify
      novel and unsuspected disease-specific pathways in SpA by a systematic and
      unbiased synovial gene expression analysis. METHODS: Differentially expressed
      genes were identified by pan-genomic microarray and confirmed by quantitative
      polymerase chain reaction and immunohistochemical analyses of synovial tissue
      biopsy samples from patients with SpA (n=63), RA (n=28), and gout (n=9). The
      effect of inflammation on gene expression was assessed by stimulating fibroblast
      like synoviocytes (FLS) with synovial fluid and by analysis of synovial tissue
      samples at weeks 0 and 12 of etanercept treatment. RESULTS: Using very stringent
      statistical thresholds, microarray analysis identified 64 up-regulated
      transcripts in patients with SpA synovitis as compared to those with RA
      synovitis. Pathway analysis revealed a robust myogene signature in this gene set.
      The myogene signature was technically and biologically reproducible, was specific
      for SpA, and was independent of disease duration, treatment, and SpA subtype
      (nonpsoriatic versus psoriatic). Synovial tissue staining identified the myogene
      expressing cells as vimentin-positive, prolyl 4-hydroxylase beta-positive, CD90+,
      and CD146+ mesenchymal cells that were significantly overrepresented in the
      intimal lining layer and synovial sublining of inflamed SpA synovium. Neither in
      vitro exposure to synovial fluid from inflamed SpA joints nor in vivo blockade of
      tumor necrosis factor modulated the SpA-specific myogene signature. CONCLUSION:
      These data identify a novel and disease-specific myogene signature in SpA
      synovitis. The fact that this stromal alteration appeared not to be downstream of
      local inflammation warrants further analysis of its functional role in the
      pathogenesis of the disease.

PMID- 22972411
TI  - The effects of AMPA receptor blockade in the prelimbic cortex on systemic and
      ventral tegmental area opiate reward sensitivity.
AB  - RATIONALE: The medial prefrontal cortex (mPFC) is a key neural region involved in
      opiate-related reward memory processing. AMPA receptor transmission in the mPFC
      modulates opiate-related reward memory processing, and chronic opiate exposure is
      associated with alterations in intra-mPFC AMPA receptor function. OBJECTIVE: The
      objectives of this study were to examine how pharmacological blockade of AMPA
      receptor transmission in the prelimbic (PLC) division of the mPFC may modulate
      opiate reward memory acquisition and whether opiate exposure state may modulate
      the functional role of intra-PLC AMPA receptor transmission during opiate reward
      learning. METHODS: Using an unbiased conditioned place preference (CPP) procedure
      in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA
      receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral
      morphine CPP conditioning, using sub-reward threshold conditioning doses of
      either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine
      (250 ng/0.5 MUl). RESULTS: We show that, in both opiate-naive and opiate
      dependent states, intra-PLC blockade of AMPA receptor transmission, but not the
      infralimbic cortex, increases the behavioral reward magnitude of systemic or
      intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling
      because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (alpha-flu), a
      broad-spectrum dopamine receptor antagonist, blocked the morphine-reward
      potentiating effects of AMPA receptor blockade. CONCLUSIONS: These findings
      suggest a critical role for intra-PLC AMPA receptor transmission in the
      processing of opiate reward signaling. Furthermore, blockade of AMPA transmission
      specifically within the PLC is capable of switching opiate reward processing to a
      DA-dependent reward system, independently of previous opiate exposure history.

PMID- 22972412
TI  - Comparison of the behavioral and cardiovascular effects of mephedrone with other
      drugs of abuse in rats.
AB  - RATIONALE: Exceedingly little experimental research exists on the popular
      recreational drug mephedrone (4-methylmethcathinone) despite clinical reports
      concerning its behavioral and cardiovascular toxicity. OBJECTIVES: To
      characterize mephedrone preclinically by examining its capacity to (1) serve as a
      discriminative stimulus, (2) disrupt the acquisition of response sequences, and
      (3) disrupt mean arterial pressure (MAP) and heart rate (HR). METHODS AND
      RESULTS: In one group of subjects that reliably discriminated 3.2 mg/kg of
      mephedrone from saline (n = 9), substitution tests indicated that stimulants
      (cocaine, MDMA, and methamphetamine) more closely approximated the mephedrone
      discriminative stimulus than non-stimulants (fenfluramine, morphine, and
      phencyclidine), although none fully substituted. In a second group (n = 6),
      mephedrone (0.56-10 mg/kg, i.p.) dose-dependently decreased response rate and
      increased errors in both components of a procedure in which subjects either
      acquired a new response sequence each session (repeated acquisition) or completed
      the same response sequence each session (performance). Finally, in a third group
      (n = 12), radio telemetry probes were used to measure the changes in MAP and HR
      elicited by mephedrone and then compared them to a known stimulant,
      methamphetamine. In these studies, mephedrone (0.01-9 mg/kg, i.v.) elicited
      increases in MAP and HR that were very similar to those elicited by
      methamphetamine (0.01-9 mg/kg, i.v.). The tachycardia and pressor responses to
      mephedrone (3 mg/kg) were blocked by the beta-blocker atenolol (1 mg/kg, i.v.)
      and the alpha1, alpha2-blocker phentolamine (3 mg/kg, i.v.), respectively.
      CONCLUSIONS: Mephedrone produces behavioral and cardiovascular responses that are
      similar to other stimulants; however, differences from the classical stimulants
      were also apparent.

PMID- 22972414
TI  - Photochemistry between a ruthenium(II) pyridylimidazole complex and benzoquinone:
      simple electron transfer versus proton-coupled electron transfer.
AB  - A ruthenium(II) complex with two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine
      chelates and a 2-(2'-pyridyl)imidazole ligand was synthesized and characterized
      by electrochemical and optical spectroscopic means. The respective complex has
      the potential to act as a combined electron-proton donor when promoted to its
      long-lived (3)MLCT excited state with visible light. The possibility of proton
      coupled electron transfer (PCET) between the ruthenium(II) complex and 1,4
      benzoquinone as an electron/proton acceptor was explored by steady-state and time
      resolved luminescence spectroscopy, as well as by transient absorption
      spectroscopy in the nanosecond time regime. Excited-state deactivation is found
      to occur predominantly via simple oxidative quenching involving no proton motion,
      but a minor fraction of the photoexcited complex appears to react via PCET since
      there is spectral evidence for semiquinone as a photoproduct. Presumably, PCET is
      not kinetically competitive with simple electron transfer because the latter
      process is sufficiently exergonic and because there is little thermodynamic
      benefit from coupling proton transfer to the photoinduced electron transfer.

PMID- 22972413
TI  - The effects of perinatal fluoxetine treatment on the circadian system of the
      adult mouse.
AB  - RATIONAL: Depression is prevalent among women of childbearing age and is
      frequently treated with selective serotonin reuptake inhibitors (SSRIs). As some
      SSRIs, such as fluoxetine (Flx), can cross the placenta, it is possible that the
      neurodevelopment of the fetus may be affected, leading to altered behavior in
      adulthood. OBJECTIVES: In this study, we examined the effects of perinatal Flx
      exposure on the subsequent expression of circadian rhythms in adult mice.
      METHODS: Dams were treated with 25 mg/kg/day Flx in their drinking water from
      embryonic day 15 to postnatal day 12. Circadian organization of wheel running
      rhythms and phase shifts to photic and non-photic stimuli were assessed in the
      offspring starting at 6 weeks of age. RESULTS: We found that perinatal Flx
      exposure led to larger light-induced phase advances (1.19 +/- 0.51 vs. 0.55 +/-
      0.25 h), smaller phase advances to the serotonin agonist 8-OH-DPAT during the mid
      subjective day (0.44 +/- 0.15 vs. 0.70 +/- 0.17 h), and a shorter free-running
      period in constant darkness (23.47 +/- 0.13 vs. 23.64 +/- 0.13 h). CONCLUSIONS:
      These results suggest that perinatal exposure to SSRIs may have consequences for
      the functioning of the circadian system later in life.

PMID- 22972415
TI  - Prognostic significance of expression of cyclooxygenase-2, vascular endothelial
      growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma.
AB  - BACKGROUND: The association between expression of cyclooxygenase-2 (COX-2),
      vascular endothelial growth factor (VEGF), epidermal growth factor receptor
      (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was
      studied. METHODS: Expression of COX-2, VEGF, and EGFR by immunohistochemical
      (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS),
      disease-free survival (DFS), locoregional control, and distant metastasis-free
      survival rates were compared for different expression levels of each marker.
      Multivariate analysis was by the Cox regression model. RESULTS: Median follow-up
      after radiation therapy +/- chemotherapy was 116 months. Univariate and
      multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage
      were all independent predictors for OS, DFS, locoregional control, and distant
      metastasis-free survival rates. CONCLUSIONS: High expression of COX-2, VEGF, and
      EGFR were independent adverse prognostic factors for long-term outcomes in
      nonmetastatic NPC independent of clinical stage.

PMID- 22972416
TI  - Stable liquid glucagon formulations for rescue treatment and bi-hormonal closed
      loop pancreas.
AB  - Small doses of glucagon given subcutaneously in the research setting by an
      automated system prevent most cases of hypoglycemia in persons with diabetes.
      However, glucagon is very unstable and cannot be kept in a portable pump.
      Glucagon rapidly forms amyloid fibrils, even within the first day after
      reconstitution. Aggregation eventually leads to insoluble gels, which occlude
      pump catheters. Fibrillation occurs rapidly at acid pH, but is absent or minimal
      at alkaline pH values of ~10. Glucagon also degrades over time; this problem is
      greater at alkaline pH. Several studies suggest that its primary degradative
      pathway is deamidation, which results in a conversion of asparagine to aspartic
      acid. A cell-based assay for glucagon bioactivity that assesses glucagon receptor
      (GluR) activation can screen promising glucagon formulations. However, mammalian
      hepatocytes are usually problematic as they can lose GluR expression during
      culture. Assays for cyclic AMP (cAMP) or its downstream effector, protein kinase
      A (PKA), in engineered cell systems, are more reliable and suitable for
      inexpensive, high-throughput assessment of bioactivity.

PMID- 22972418
TI  - Pro-apoptotic properties of morphine in neuroblastoma * glioma NG108-15 hybrid
      cells: modulation by yohimbine.
AB  - Short-term incubation with pharmacologically relevant concentrations of morphine
      has been shown to transiently affect the metabolism and redox status of NG108-15
      cells through delta-opioid receptor stimulation, but apparently did not provoke
      cell death. The present work tries to determine if incubation with morphine at
      longer time intervals (24 h) provokes apoptosis and/or necrosis, as it has been
      described in other cell lines. We have also checked the potential modulatory role
      of yohimbine on these effects, on the basis of the previously described
      interactions between this drug and opioid receptor ligands. Incubation with
      morphine 0.1 and 10 MUM provoked the appearance of images compatible with
      apoptosis (bebbling, pyknotic cells with cytoplasmic and nuclear condensation)
      and necrosis (cells swollen with vacuolated cytoplasm lacking cell processes)
      that could be observed directly and/or after staining with methylene blue,
      crystal violet and propidium iodide/4',6-diamidino-2-phenylindole (IP/DAPI).
      Quantification of apoptosis by activation of caspases 3 and 7 and DNA
      fragmentation with the Tunel assay revealed a modest but significant increase
      after incubation with the two concentrations of morphine used. Co-incubation with
      10 MUM yohimbine prevented all these effects of the opioid. The results extend
      previous findings of a yohimbine-sensitive, neurotoxic effect of morphine on
      NG108-15 cells.

PMID- 22972417
TI  - Oxidative stress-related lung dysfunction by chromium(VI): alleviation by Citrus
      aurantium L.
AB  - Chromium(VI), a very strong oxidant, causes high cytotoxicity through oxidative
      stress in tissue systems. Our study investigated the potential ability of
      ethanolic Citrus aurantium L., family Rutaceae extract, used as a nutritional
      supplement, to alleviate lung oxidative damage induced by Cr(VI). A high
      performance liquid chromatography coupled with a mass spectrometer method was
      developed to separate and identify flavonoids in C. aurantium L. Six flavonoids
      were identified, as (1) poncirin, (2) naringin, (3) naringenin, (4) quercetin,
      (5) isosinensetin, and (6) tetramethyl-o-isoscutellarein. Adult Wistar rats, used
      in this study, were divided into six groups of six animals each: group I served
      as controls which received standard diet, group II received via drinking water
      K2Cr2O7 alone (700 ppm), groups III and IV were pretreated for 10 days with
      ethanol extract of C. aurantium L. at doses of 100 and 300 mg/kg body weight/day,
      respectively, and then K2Cr2O7 was administrated during 3 weeks, and groups V and
      VI received during 10 days only C. aurantium L. ethanol extract at doses of 100
      and 300 mg/kg/day, respectively. Ethanol extract of C. aurantium L. was
      administered orally. Rats exposed to Cr(VI) showed in lung an increase in
      malondialdehyde and protein carbonyl levels and a decrease in sulflydryl content,
      glutathione, nonprotein thiol, and vitamins C and E levels. Decreases in enzyme
      activities such as in Na(+)K(+) ATPase, catalase, glutathione peroxidase, and
      superoxide dismutase were noted. Pretreatment with C. aurantium L. of chromium
      treated rats ameliorated all biochemical parameters. Lung histological studies
      confirmed the biochemical parameters and the beneficial role of C. aurantium L.

PMID- 22972419
TI  - Preoperative levels of bilirubin or creatinine adjusted by age can predict their
      reversibility after implantation of left ventricular assist device.
AB  - BACKGROUND: It is often difficult to predict reversibility of liver or renal
      function after left ventricular assist device (LVAD) implantation in patients
      with stage D heart failure. METHODS AND RESULTS: Data were obtained for 69
      patients who had received a LVAD (18 continuous-flow, 51 pulsatile). Persistent
      hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or
      creatinine (Cre) >1.5mg/dl at 6 months after LVAD implantation. TB score or Cre
      score was calculated: 0.15 * age+1.1 * (preoperative TB) or 0.2 * age+3.6 *
      (preoperative Cre), in which coefficients were determined on the basis of odds
      ratios for persistent hepatic or renal dysfunction, respectively. Receiver
      operating characteristics analyses showed good predictabilities for persistent
      end-organ dysfunction (area under curve: 0.794 for TB score and 0.839 for Cre
      score). High-risk strata of TB score (>11.0 points) or Cre score (>14.1 points)
      were associated with persistently higher levels of TB or Cre (TB, 1.32 +/- 0.51;
      Cre, 1.23 +/- 0.41 mg/dl; both P<0.001 vs. low-risk strata). CONCLUSIONS:
      Reversibility of end-organ function with LVAD implantation can be well predicted
      by our new risk scoring system that consists of the preoperative TB or Cre level
      adjusted by the patient's age. The scoring system would be beneficial, especially
      in considering the indication of a bridge to candidacy.

PMID- 22972420
TI  - Optically and electrically controlled circularly polarized emission from
      cholesteric liquid crystal materials doped with semiconductor quantum dots.
AB  - Novel types of electro- and photoactive quantum dot-doped cholesteric materials
      have been engineered. UV-irradiation or electric field application allows one to
      control the degree of circular polarization and intensity of fluorescence
      emission by prepared quantum dot-doped liquid crystal films.

PMID- 22972421
TI  - Sulfatides inhibit adhesion, migration, and invasion of murine melanoma B16F10
      cell line in vitro.
AB  - Endogenous sulfatide, such as 3-sulfated galactosylceramide (3-sulfatide) has
      been reported to be involved in neuronal development and regulation of tumor cell
      metastasis. Recently, a new 6-sulfated glucosylceramide (6-sulfatide) has been
      isolated from the ascidian, Ciona intestinalis. To determine the antitumor
      function of the new sulfatide, we examined the effects of synthetic 6-sulfatide
      and 3-sulfatide on the metastatic features of a murine melanoma cell line,
      B16F10. Both sulfatides significantly inhibited the adhesion of melanoma cells
      onto fibronectin-coated tissue plates and, the motility and invasion of the
      cells, with 6-sulfatide showing stronger inhibitory activities. In addition, both
      sulfatides inhibited alpha(5)-, and beta(1)- but not alpha(v)- or beta(3)
      integrin expression. Furthermore, these sulfatides inhibited the activation of
      focal adhesion kinase, Akt, and extracellular signal-regulated kinase signaling
      pathways, which are thought to be important for cell migration and invasion.
      Therefore, these sulfatides may serve as promising drug candidates for the
      treatment of cancer metastasis.

PMID- 22972422
TI  - The round window: is it the "cochleostomy" of choice? Experience in 130
      consecutive cochlear implants.
AB  - OBJECTIVE: To demonstrate that the round window insertion (RWI) for cochlear
      implantation with multichannel electrodes is a reliable, safe, and effective
      technique. STUDY DESIGN: Retrospective case review. SETTING: Academic tertiary
      referral center. PATIENTS: One hundred thirty consecutive cochlear implants (72
      female and 58 male subjects) performed from August 2009 to August 2011. Devices
      included 83 Cochlear, 40 Med El, and 7 Advanced Bionics (AB) cochlear implants.
      INTERVENTION: Subsequent to a full audiometric assessment, patients underwent a
      mastoidectomy with facial recess approach whereby the primary surgical objective
      was to perform a RWI. When the surgeon was unable to access the round window
      safely, a cochleostomy was performed anterior and inferior to the round window.
      Postoperative performance was measured with Hearing in Noise Test, the Consonant
      Nucleus-Consonant test, and/or the Arizona Biomedical Sentences test. MAIN
      OUTCOME MEASURES: Surgical feasibility of reliably performing a RWI, reason for
      cochleostomy, postoperative complications, and audiometric performance. RESULTS:
      In 111 (85.4%) of 130 procedures, a RWI was performed; in 19 (14.6%), a
      cochleostomy was readily performed by the same approach. Reasons for creating a
      cochleostomy included facial nerve and jugular bulb location. There were no major
      postoperative complications in either group and 13 total minor complications.
      There was no statistically significant difference in postoperative complications
      or in audiometric performance between the 2 groups. CONCLUSION: The RWI may offer
      several advantages over a cochleostomy, and it seems to be a reliable, safe, and
      effective technique for cochlear implantation with today's cochlear implant
      electrodes. Further studies would be necessary to verify these findings for broad
      application to the cochlear implant patient population.

PMID- 22972423
TI  - Stimulation rate reduction and auditory development in poorly performing cochlear
      implant users with auditory neuropathy.
AB  - OBJECTIVE: Patients with auditory neuropathy spectrum disorder (ANSD) exhibit
      altered neural synchrony in response to auditory stimuli. It has been
      hypothesized that a slower rate of electrical stimulation in programming
      strategies for cochlear implant (CI) users with ANSD may enhance development of
      neural synchrony and speech perception abilities. STUDY DESIGN: Retrospective
      case series. SETTING: Tertiary otologic practice. PATIENTS: Twenty-two patients
      with ANSD underwent CI. Patients with complete postoperative audiometric data and
      at least 2 years of follow-up were included in further analysis. INTERVENTION:
      Thirteen patients patients met inclusion criteria. Five "poorly performing" CI
      recipients with ANSD who had not developed closed-set speech perception abilities
      despite at least 2 years of implant use underwent implant programming to lower
      the neural stimulation rate. MAIN OUTCOME MEASURES: Speech perception abilities
      over time using parent questionnaire, closed-set testing, and open-set measures.
      RESULTS: A high incidence of comorbid conditions was present in the poor
      performers, including cognitive delay (n = 2), motor delay (n = 3), and autism
      spectrum disorder (n = 1). The median time to rate slowing in 5 poor performers
      was 29 months after implant activation. Three of 5 patients achieved closed-set
      speech perception scores higher than 60% after 6 to 16 months of implant use at
      the slower rates. At last follow-up (median, 42 mo), no poor performer had yet
      achieved open-set speech perception abilities. Of all CI recipients with ANSD
      included in analysis, open-set speech perception abilities developed in 46%
      (6/13). CONCLUSION: In CI recipients with ANSD who demonstrate limited auditory
      skills development despite prolonged implant use, lowering the stimulation rate
      may facilitate acquisition of closed-set speech perception abilities. Further
      efforts on the study of programming parameters in ANSD patients with CIs are
      necessary to maximize auditory development in this patient population.

PMID- 22972424
TI  - Petrous bone fractures violating otic capsule.
AB  - OBJECTIVE: This study presents our experience with a series of patients suffering
      from petrous bone fractures violating the otic capsule who underwent subtotal
      petrosectomy combined with eustachian tube, middle ear, and mastoid obliteration,
      with the goal of preventing cerebrospinal fluid (CSF) leak and meningitis.
      METHODS: This study enrolled 26 patients between 1997 and 2011. The clinical
      symptoms, otoscopy, and preoperative and postoperative audiometry and facial
      function, as well as CSF leak or meningitis, were evaluated in each patient. The
      entire group underwent a subtotal petrosectomy using the technique described in
      detail by Fisch. In addition, each patient was interviewed using a questionnaire
      to evaluate the impact on quality of life. RESULTS: Intraoperatively, we found
      significant CSF leaks in 14 patients (42.5%). No patient reported other episodes
      of CSF leak or meningitis after the surgery. The patients' responses of facial
      nerve function were slightly worse than the House-Brackmann evaluation (50%
      versus 42.3%; p < 0.05). The vast majority (88.5%) of the patients experienced no
      social impact. CONCLUSION: Our findings suggest the importance of not
      underestimating the risk for CSF leak in the petrous bone fractures violating the
      otic capsule. Preoperative counseling regarding the various troublesome
      complications must adequately motivate candidates to undergo surgery by pointing
      out the positive impact of the proposed treatment.

PMID- 22972425
TI  - Adipose replacing intracochlear architecture after meningioma removal.

PMID- 22972427
TI  - Can the OCT replace functional tests such as the mfERG?

PMID- 22972428
TI  - Testing endothelial function and its clinical relevance.
AB  - Endothelial dysfunction as an integrating index of the risk factor burden and
      genetic susceptibility is an early marker of atherothrombotic disease. Therefore,
      tremendous interest exists in its measurement and determination of the clinical
      utility of the evaluation of endothelial function.Different invasive and non
      invasive techniques exist for exploring various aspects of the pathobiology of
      the endothelium. As endothelial dysfunction is a diffuse-systemic disorder, the
      peripheral arteries, because of their accessibility, represent the basis for
      assessment of endothelial dysfunction. Flow-mediated dilation (FMD) of the
      peripheral conduit arteries is one of the most widely used tests of endothelial
      function. FMD measures the endothelial vasomotor response during reactive
      hyperemia, but it does not provide information concerning the control of arterial
      tone at rest. A new technique, low-flow-mediated constriction (L-FMC), provides
      complementary information to that by FMD, quantifying the decrease in the forearm
      conduit artery diameter that occurs in response to the decrease in blood flow
      during occlusion. This indicated that the L-FMC response is not based on nitric
      oxide availability but it might be mediated by other substances, providing a
      coordinated effect of vasodilation and its inhibition; therefore, simultaneous
      determination of FMD and L-FMC may provide comprehensive information on vascular
      homeostasis.Peripheral arterial tonometry (PAT) evaluates pulse wave amplitude,
      which is linked to endothelial function. Like FMD, PAT has also been shown to be
      reduced in the presence of risk factors, as well as in patients with
      atherosclerosis; however, FMD of the brachial artery and PAT are very different
      methods for identification of the vascular reactivity of different arterial
      territories. FMD directly registers the dilation capability of the large-conduit
      artery, whereas PAT measures flow response hyperemia, which is related to the
      endothelial function of small arteries and to the endothelial function of the
      microcirculation. Therefore, this technique is mostly used for investigation of
      the functional capability of the microcirculation.Determination of venous
      endothelial dysfunction is more complicated and invasive and is less
      reproducible. Micro-invasive techniques such as the dorsal hand vein technique
      and radionuclide assessment of changes in volume of the legs provide limited
      information about venous endothelial health; however, as endothelial dysfunction
      is expected to be a systemic disorder affecting the complete circulatory system,
      determination of the endothelial function of peripheral arteries also gives
      insight into venous functional status.

PMID- 22972429
TI  - Expression of endothelial lipase correlates with the size of neointima in a
      murine model of vascular remodeling.
AB  - AIM: Endothelial lipase (EL) regulates plasma high-density lipoprotein
      cholesterol (HDL-C) levels by promoting HDL catabolism. However, it remains
      unknown whether the inhibition of EL has beneficial effects on the genesis of
      vascular diseases. Here, we investigated the role of EL on vascular remodeling in
      mice. METHODS: Vascular remodeling was developed by ligation of the left common
      carotid artery and neointimal lesions were histologically compared between EL
      knockout (ELKO), EL-transgenic (ELTg), and wild-type (WT) mice. HDL was isolated
      from these mice, and effects of the HDL on cell growth and Erk activation were
      evaluated in vitro using cultured vascular smooth muscle cells. RESULTS: Plasma
      HDL-C levels were 62% higher in ELKO and 13% lower in ELTg than in WT mice, after
      the carotid ligation. The size of neointimal lesion was significantly larger in
      ELTg and smaller in ELKO than in WT mice. Vascular expression of adhesion
      molecules was lower in ELKO and higher in ELTg compared with WT mice. Moreover,
      oxidative stress was attenuated in ELKO mice. HDL isolated from ELKO, ELTg, and
      WT mice inhibited expression of intercellular adhesion molecule-1, angiotensin II
      induced activation of Erk, and growth of cultured vascular smooth muscle cells,
      whereas EL expression itself did not affect cell migration or growth. CONCLUSION:
      EL expression modulates vascular remodeling as well as plasma HDL-C levels. EL
      inactivation may increase HDL particles that can inhibit smooth muscle cell
      growth and migration.

PMID- 22972430
TI  - Circulating adiponectin levels and their associated factors in young lean healthy
      Japanese women.
AB  - AIM: The aim of the current study was to investigate circulating adiponectin
      levels and their associated factors in young lean healthy Japanese women.
      METHODS: We recruited 82 healthy Japanese women in their twenties and thirties
      with their body mass index <25 kg/m(2), and performed anthropometric,
      sphygmomanometric, and laboratory examinations. Laboratory examinations included
      adiponectin levels, as well as lipid profiles, glucose, hemoglobin A1c,
      transaminase, and creatinine levels, from which the glomerular filtration rate
      was estimated (eGFR). RESULTS: The median and interquartile range of circulating
      adiponectin levels were 8.1 (6.2-10.0) ug/ mL. HDL cholesterol levels and eGFR,
      but not the other examined clinical parameters, were significantly correlated
      with log-transformed adiponectin levels; their correlation coefficients were
      0.323 (p<0.01) and -0.311 (p<0.01), respectively. Statistical significance was
      still observed even after adjustment for each other (both p= 0.02). In adjusted
      models, subjects with HDL cholesterol levels >=80 mg/dL had 1.3 times higher
      adiponectin levels than those with 40-60 mg/dL, whereas eGFR >=110
      mL/min/1.73m(2) and 60-90 mL/min/1.73m(2) showed a 1.5-fold difference in
      adiponectin levels. CONCLUSIONS: Adiponectin levels of young lean healthy
      Japanese women had significant associations with HDL cholesterol levels and eGFR,
      even though their HDL cholesterol levels and eGFR were distributed within normal
      ranges. It seems important to take into account these two variables in evaluating
      adiponectin levels of these subjects, even if the two variables are within normal
      ranges.

PMID- 22972431
TI  - Comparison of the impact of changes in waist circumference and body mass index in
      relation to changes in serum gamma-glutamyltransferase levels.
AB  - AIM: Serum gamma-glutamyltransferase (GGT) levels, which are associated with
      insulin resistance, may predict the incidence of cardiovascular disease and
      mortality. Here, the relationship was analyzed between changes in obesity
      parameters and those in serum GGT over a one-year period. METHODS: Data were
      analyzed from individuals who underwent general health screening two years
      running. RESULTS: Among 3086 individuals (1954 men, 1132 women), percent changes
      in both waist circumference (%dWC) and body mass index (BMI) (%dBMI) were
      significantly correlated with percent changes in GGT (%dGGT) in men (r=0.17 and
      r=0.31, respectively). On the other hand, in women, %dBMI, but not %dWC, had a
      significant association with %dGGT. When age, %dWC, %dBMI, smoking status, and
      alcohol intake were all included as independent variables, %dBMI, but not %dWC,
      showed a graded association with the highest %dGGT quartile in both genders.
      Furthermore, incorporation of %dWC as an additional independent variable to age,
      gender, and %dBMI did not show an incremental improvement in prediction for the
      highest %dGGT quartile (C statistic, 0.643 to 0.648; p= 0.380), suggesting that
      taking WC changes into account does not significantly improve the prediction of
      GGT changes when BMI has already been taken into consideration. CONCLUSION:
      Changes in BMI are dose-dependently associated with GGT changes in both genders;
      however, the additional consideration of changes in WC does not show a
      significant statistical improvement in the prediction of GGT changes.

PMID- 22972432
TI  - An investigation into the feasibility of myoglobin-based single-electron
      transistors.
AB  - Myoglobin single-electron transistors were investigated using nanometer-gap
      platinum electrodes fabricated by electromigration at cryogenic temperatures.
      Apomyoglobin (myoglobin without the heme group) was used as a reference. The
      results suggest single-electron transport is mediated by resonant tunneling with
      the electronic and vibrational levels of the heme group in a single protein. They
      also represent a proof-of-principle that proteins with redox centers across
      nanometer-gap electrodes can be utilized to fabricate single-electron
      transistors. The protein orientation and conformation may significantly affect
      the conductance of these devices. Future improvements in device reproducibility
      and yield will require control of these factors.

PMID- 22972433
TI  - Islet-derived stem cells from adult rats participate in the repair of islet
      damage.
AB  - This study investigated the role of adult islet-derived stem cells in repairing
      islet damage. Using intraperitoneal injection of cerulein, a rat model of acute
      pancreatitis was induced in an experimental group. The expression of the protein
      c-kit, a pancreatic stem cell marker, was observed using immunohistochemistry at
      set intervals following successful model preparation. Pathological changes in
      pancreatic tissues were also observed using routine hematoxylin and eosin
      staining. Cells with positive c-kit staining were rarely observed in normal
      tissues. At all observation intervals after the induction of acute pancreatitis,
      c-kit staining was restricted to the islets. Over the course of observations,
      staining changed from low to high intensity, and then back to low intensity
      again. The primary pathological manifestation in the experimental group was
      edematous pancreatic tissues with local necrotic lesions. These findings
      suggested that c-kit positive cells are likely to be a type of pancreatic
      progenitor cell that is involved only in the self-repair of islet damage and does
      not migrate.

PMID- 22972434
TI  - Light and electron-microscopic study of leucine enkephalin immunoreactivity in
      the cat claustrum.
AB  - The claustrum is a complex telencephalic structure owing to its reciprocal
      connectivity with most--if not all--cortical areas. However, there is a paucity
      of data in the literature concerning its histochemical components, including
      opioid peptide neurotransmitters. The aim of the present study was to examine the
      morphology, distribution and ultrastructure of leucine-enkephalin-immunoreactive
      (Leu-enk-ir) neurons and fibers in the dorsal claustrum (DC) of the cat. Seven
      healthy, adult male and female cats were used in our study. All animals received
      humane care. They were irreversibly anesthetized and transcardially perfused with
      fixative. Brains were removed, postfixed, blocked and sectioned. Sections were
      incubated with polyclonal anti-Leu-enk antibodies using the Avidin-Biotin
      Peroxidase Complex method. Leu-enk-ir neurons and fibers were distributed
      throughout the DC. Some of the neurons were lightly-stained, while others were
      darkly-stained. Light-microscopically, they varied in shape: oval, fusiform,
      multipolar and irregular. With regard to size, they were categorized as small (15
      MUm or less in diameter), medium (16-20 MUm in diameter) and large (21 MUm or
      more in diameter). No specific pattern of regional distribution was found. On the
      electron microscope level, immunoproduct was observed in neurons, dendrites and
      terminal boutons. Different types of Leu-enk-ir neurons differ in their
      ultrastructural features, including two types of synaptic boutons. No gender
      specific features were observed. In conclusion, it is our hope that our study
      will serve to contribute to a better understanding of the functional neuroanatomy
      of the DC in the cat, and that it can be extrapolated and applied to other
      mammals, including humans.

PMID- 22972435
TI  - Expression of FSH and its co-localization with FSH receptor and GnRH receptor in
      rat cerebellar cortex.
AB  - The expression of follicle-stimulating hormone (FSH) and its receptor in
      extrapituitary and non-HPG axis tissues has been demonstrated and their non
      reproductive functions in these tissues have been found. However, there have been
      no reports concerning the expression and function of FSH and its receptor in the
      cerebellum. In our study, immunofluorescence staining and in situ hybridization
      were used to detect the expression of FSH, double-labeled immunofluorescence
      staining was used to detect co-localization of FSH and its receptor and co
      localization of FSH and gonadotropin-releasing hormone (GnRH) receptor in the rat
      cerebellar cortex. Results showed that some cells of the Purkinje cell layer,
      granular layer, and molecular layer of the cerebellar cortex showed both FSH
      immunoreactivity and FSH mRNA positive signals; not only for FSH and FSH
      receptor, but also for FSH and GnRH receptor co-localized in some cells
      throughout the Purkinje cell layer, granular layer, and molecular layer of the
      cerebellar cortex. These suggested that rat cerebellum could express FSH;
      cerebellum is a target tissue of FSH; FSH may exert certain functions through FSH
      receptor in a paracrine or autocrine manner; GnRH may regulate FSH positive cells
      through GnRH receptor in the cerebellum. Our study provides morphological
      evidence for further functional research on FSH and related hormones in the
      cerebellum.

PMID- 22972436
TI  - Dietary patterns and the risk of type 2 diabetes in overweight and obese
      individuals.
AB  - PURPOSE: Although overweight is an important determinant of diabetes risk, it
      remains unclear whether food choices can still influence the risk for type 2
      diabetes in overweight persons. In this paper, we aim to clarify the role of
      dietary patterns in the development of type 2 diabetes in overweight and obese
      individuals. METHODS: We studied 20,835 overweight and obese participants in the
      Dutch part of the European Investigation into Cancer and Nutrition (EPIC-NL)
      study. Dietary intake was measured using a validated food frequency
      questionnaire, and dietary patterns were generated using factor analysis.
      Incident type 2 diabetes was verified against medical records. Cox proportional
      hazards models were used to assess the association between the dietary patterns
      (factor scores categorized in quartiles) and incident type 2 diabetes. RESULTS:
      Scoring on Pattern 1, characterized by fish, wine, chicken, raw vegetables and
      fruit juices, was not associated with type 2 diabetes risk after confounder
      adjustment. A high score on Pattern 2, characterized by soft drinks, fries and
      snacks, was associated with higher risk of type 2 diabetes (HR Q4 vs. Q1 (95 %
      CI): 1.70 (1.31; 2.20), P(trend) <= 0.0001), particularly among less active
      individuals [less active: HR Q4 vs. Q1 (95 % CI): 2.14 (1.48; 3.09), P(trend) =
      0.00004, more active: HR Q4 vs. Q1 (95 % CI): 1.35 (0.93; 1.97), P(trend) = 0.01;
      P(interaction) = 0.02]. CONCLUSIONS: A high score on a pattern high in soft
      drinks, fries and snacks and low in fruit and vegetables was associated with
      higher risk of type 2 diabetes in overweight and obese subjects especially among
      physically less active individuals.

PMID- 22972438
TI  - Silencing of CXCR4 by RNA interference inhibits cell growth and metastasis in
      human renal cancer cells.
AB  - Renal cell carcinoma (RCC) is the third most common genitourinary malignancy,
      accounting for 3% of cancer in adults. The mortality and morbidity of RCC is
      strongly associated with its high propensity to metastasize to specific organs.
      This may be attributed to the fact that the CXCR4 G protein-coupled receptor
      (GPCR) on RCC cells mediates chemoattraction toward stromal-derived factor 1 (SDF
      1) secreted by target organs. RNA interference (RNAi), which has been proven to
      be a powerful tool for suppressing gene expression, may lead to novel strategies
      for treating RCC. Our previous experiments confirmed that RCC A-498 cells
      overexpressing CXCR4 are associated with increased invasiveness. In this study,
      we constructed recombinant CXCR4-RNAi plasmids and transfected them into A-498
      cells in vitro. Reverse transcription polymerase chain reaction (RT-PCR) and
      western blotting revealed that CXCR4 was downregulated in transfected cells
      compared with control cells. Our results from MTT and transwell migration assays
      indicated that specific downregulation of CXCR4 inhibited cell growth,
      invasiveness and migration. Flow cytometric analysis indicated that silencing of
      CXCR4 in A-498 cells by RNA interference induced cell apoptosis in RCC in vitro.
      Thus, siRNA targeting of CXCR4 can effectively inhibit the growth and metastasis
      of RCC cells and may be a promising innovative anticancer therapy.

PMID- 22972437
TI  - Comparison of three societally derived health-state classification values among
      older African Americans with depressive symptoms.
AB  - PURPOSE: To compare societal values across three health-state classification
      systems in older African Americans with depression and to describe the
      association of these instruments to depression severity. METHODS: We summarized
      baseline values for EQ-5D (US weights) and HUI2/3 (Canadian weights) and their
      subscales for 118 older African American participants enrolled in a randomized
      depression treatment trial and calculated correlations between the different
      instruments. We evaluated ceiling and floor effects for each instrument by
      comparing the proportion at the highest and lowest possible score for each tool.
      Also, utility scores were assessed by level of depression severity (mild,
      moderate, moderate severe, severe) scores as measured by the Patient Health
      Questionnaire (PHQ-9). RESULTS: Mean utility values were 0.58 (SD = 0.21) for EQ
      5D, 0.52 (SD = 0.21) for HUI2, and 0.36 (SD = 0.31) for HUI3. For the EQ-5D, 72 %
      of participants reported having some problems on the anxiety/depression domain.
      On the emotion domain for the HUI2, 23 % reported the highest level of impairment
      compared to only 3 % on the HUI3. No participant scored at the floor for the EQ
      5D, HUI2, or HUI3 index; one participant scored at the ceiling value on the HUI3
      index. Correlations ranged from 0.63 to 0.82 (all of which were significant at an
      alpha level of 0.05). In general, utility scores trended inversely with
      depression level. CONCLUSION: Small differences in the three preference-weighted
      health-state classification systems were evident for this sample of older African
      Americans with depressive symptoms, with HUI scores lower than EQ-5D. For this
      sample, utility scores were lower (i.e., poorer) than the general United States
      population with depression on each utility measure.

PMID- 22972439
TI  - The epidemiology of urinary incontinence and it's influence on quality of life in
      Taiwanese middle-aged women.
AB  - AIM: To evaluate the prevalence and risk factors of urinary incontinence (UI) and
      its effects on quality of life in women aged between 35 and 64 years. METHODS:
      Data were obtained from the 2005 National Health Interview survey, in which 4,661
      women aged between 35 and 64 years responded to questions concerning UI
      occurrence and health-related quality of life (HRQL), assessed using the Short
      Form 36, Taiwan version. Chi-square tests and multiple logistic regressions were
      applied to analyze comorbidity and risk factors of UI. Multivariable liner
      regression was used to evaluate the association between UI and HRQL. RESULTS: The
      weighted UI prevalence in Taiwanese women aged 35-44, 45-54 years, and 55-64
      years were 14.7%, 24.7%, and 32.4%, respectively. After adjustment, increased
      age, greater parity, higher BMI (body mass index), former HRT use, having a
      psychiatric disease, hyperlipidemia, and respiratory disease were identified as
      significant UI risk factors. Women with UI had significantly lower scores on all
      SF-36 dimensions. After adjusting for other factors, UI remained a significant
      predictor of all domains of SF-36 and was associated with reduced physical (by
      2.31 points) and mental (by 2.76 points) component summary scores. From a mental
      health perspective, UI had a greater influence on HRQL than diabetes,
      hyperlipidemia, and chronic kidney disease. CONCLUSION: The UI prevalence of
      Taiwanese women is high, and its negative effects on quality of life are greater
      than those of other major chronic conditions, but are often overlooked and seldom
      intervened.

PMID- 22972440
TI  - The application of biochemical responses to assess environmental quality of
      tropical estuaries: field surveys.
AB  - A battery of biomarkers of exposure (EROD, DBF, GST and GPx) and effect (lipid
      peroxidation and DNA damage - strand breaks) were analyzed in gill tissues from
      caged and native oysters Crassostrea rhizophorae exposed to two tropical
      estuarine systems in SW Brazil: Santos (S1, S2, S3, S4) and Paranagua (P1 -
      control, P2, P3, P4). The exposure lasted 28 days. Native oysters were sampled in
      the same areas where caged systems were exposed. Significant induction of
      biomarkers of exposure to organic compounds and oxidative stress (p < 0.05) were
      observed in all transplanted individuals from Santos resulting in DNA damage and
      lipid peroxidation. Biological adverse effects were more evident in oysters
      transplanted in the Santos Estuarine System, a recognized contaminated area, than
      in the Paranagua Estuarine System, surrounded by urban areas and Environmental
      Protected Areas. Native specimens from both estuaries showed adaption to the
      impacts of several contamination sources affecting the ecosystem. The use of
      transplanted C. rhizophorae proved to be a suitable tool for assessing and
      monitoring the environmental quality in mangrove ecosystems. This integrated
      approach employing multi-biomarker responses under field conditions could be
      incorporated as a descriptor of health status in tropical estuarine systems.

PMID- 22972441
TI  - Genetic and environmental factors associated with type 2 diabetes and diabetic
      vascular complications.
AB  - Faced with a global epidemic of type 2 diabetes (T2D), it is critical that
      researchers improve our understanding of the pathogenesis of T2D and related
      vascular complications. These findings may ultimately lead to novel treatment
      options for disease prevention or delaying progression. Two major paradigms
      jointly underlie the development of T2D and related coronary artery disease,
      diabetic nephropathy, and diabetic retinopathy. These paradigms include the
      genetic risk variants and behavioral/environmental factors. This article
      systematically reviews the literature supporting genetic determinants in the
      pathogenesis of T2D and diabetic vasculopathy, and the functional implications of
      these gene variants on the regulation of beta-cell function and glucose
      homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk
      variants, and describe the genetic technologies that have uncovered them. Also,
      genomic linkage between obesity and T2D is discussed. There is a complementary
      role for behavioral and environmental factors modulating the genetic
      susceptibility and diabetes risk. Epidemiological and clinical data demonstrating
      the effects of behavioral and novel environmental exposures on disease expression
      are reviewed. Finally, a succinct overview of recent landmark clinical trials
      addressing glycemic control and its impact on rates of vascular complications is
      presented. It is expected that novel strategies to exploit the gene- and exposure
      related underpinnings of T2D will soon result.

PMID- 22972443
TI  - Telephone counseling intervention improves dietary habits and metabolic
      parameters of patients with the metabolic syndrome: a randomized controlled
      trial.
AB  - BACKGROUND: Patients with the metabolic syndrome (MetS) can suffer from poor
      metabolic parameters through lack of adherence to requisite lifestyle changes in
      dietary and physical activity. Usually, interventions in MetS patients are
      infrequent face-to-face consultations. The low frequency or absence of counseling
      interviews leads to a shortage of information and motivation to adhere to the
      recommended lifestyle changes. Telephone interventions could be an additional low
      cost tool for effective interventions. AIM: To evaluate the effectiveness of
      telephone intervention in improving lifestyle habits and metabolic parameters in
      MetS patients compared with similar face-to-face or a usual care interventions.
      METHODS: Eighty-seven MetS patients recruited from the outpatient clinic of a
      major public hospital were randomly assigned to one of the three intervention
      groups: "usual care", "telephone" or "face-to-face". At the beginning of the
      study, all patients were provided with a hypocaloric Mediterranean-type diet.
      Afterwards, patients in the telephone group received 7 dietary counseling calls,
      patients in the face-to-face group participated in 7 one-to-one dietary
      counseling sessions, while patients in the usual care group received no other
      contact until the end of the study, 6 months later. All patients underwent full
      medical and nutritional evaluation at the beginning and at the end of the
      intervention. RESULTS: At the end of the intervention, 42% of the participants no
      longer showed symptoms of MetS; the reduction rates differed significantly
      between the groups (p = 0.024), with those in the face-to-face and telephone
      group exhibiting similar rates (52% and 54%, respectively, vs. 21% in the usual
      care group). Between-group analysis revealed that the face-to-face group achieved
      the greatest improvement in metabolic parameters, while the telephone group had
      the greatest improvement in dietary adherence compared with the usual care group.
      CONCLUSIONS: Telephone counseling is an effective way to implement behavioral
      counseling to improve lifestyle habits in MetS patients.

PMID- 22972442
TI  - The diabetic lung--a new target organ?
AB  - Several abnormalities of the respiratory function have been reported in patients
      with type 1 and type 2 diabetes. These abnormalities concern lung volume,
      pulmonary diffusing capacity, control of ventilation, bronchomotor tone, and
      neuroadrenergic bronchial innervation. Many hypotheses have emerged, and
      characteristic histological changes have been described in the "diabetic lung",
      which could explain this abnormal respiratory function. Given the specific
      abnormalities in diabetic patients, the lung could thus be considered as a target
      organ in diabetes. Although the practical implications of these functional
      changes are mild, the presence of an associated acute or chronic pulmonary and/or
      cardiac disease could determine severe respiratory derangements in diabetic
      patients. Another clinical consequence of the pulmonary involvement in diabetes
      is the accelerated decline in respiratory function. The rate of decline in
      respiratory function in diabetics has been found to be two-to-three times faster
      than in normal non-smoking subjects, as reported in longitudinal studies. This
      finding, together with the presence of anatomical and biological changes similar
      to those described in the aging lung, indicates that the "diabetic lung" could
      even be considered a model of accelerated aging. This review describes and
      analyses the current insight into the relationship of diabetes and lung disease,
      and suggests intensifying research into the lung as a possible target organ in
      diabetes.

PMID- 22972444
TI  - Quality of life and patient-perceived difficulties in the treatment of type 2
      diabetes.
AB  - BACKGROUND: Clinical evidence points to patient-perceived difficulties and
      compliance problems in implementing early insulin therapy. Therefore, individual
      treatment aims are necessary to optimize diabetes therapy, as currently
      acknowledged by the new ADA/EASD guidelines. Better characterization of patient
      perceived difficulties in the implementation of early insulin treatment may
      contribute to improved compliance and optimal tailoring of treatment regimens for
      the individual patient. OBJECTIVES: To assess differences in quality of life
      (QoL) and patient-perceived difficulties in health care with every addition of
      oral hypoglycemic agents (OHAs) and insulin therapy. METHODS: The analysis was
      conducted on a cross-sectional sample of 714 diabetic patients treated with OHAs
      or with insulin once or twice daily. Differences in diabetes-specific QoL,
      overall QoL, and perception of difficulties associated with specific diabetes
      treatment attributes were evaluated using trend analysis and comparisons between
      groups. The contribution of each diabetes treatment attribute to QoL measures and
      glycemic control was also assessed. RESULTS: No significant differences were
      found in QoL measures among patients treated exclusively with OHAs when these
      patients were assessed by the number of oral agents, irrespective of the degree
      of glycemic control. Better controlled patients treated with 2 OHAs, compared
      with poorly controlled patients treated with a single OHA, had a lower perception
      of difficulties associated with diabetes treatment attributes. Poorly controlled
      patients treated with 2 OHAs and better controlled patients treated with 3 OHAs
      had similar QoL and perceived difficulties with care. However, the insulin-based
      alternative was consistently associated with a significantly higher perception of
      pain and lower overall QoL when compared with the oral regimens. Multivariate
      models accounted for 52% and 32% of the variance in QoL measures. CONCLUSIONS:
      From the patients' perspective, oral therapy is the preferred strategy for
      attaining the treatment goals since the addition of OHAs was not associated with
      lower QoL or patient-perceived difficulties with care. If early insulin treatment
      is considered, physicians should address specific diabetes treatment
      characteristics, mainly the issue of pain, to promote improved QoL and disease
      control.

PMID- 22972445
TI  - Computational intelligence-based diagnosis tool for the detection of prediabetes
      and type 2 diabetes in India.
AB  - BACKGROUND: The incidence of diabetes is increasing rapidly across the globe.
      India has the highest proportion of diabetic patients, earning it the doubtful
      distinction of the 'diabetes capital of the world'. Early detection of diabetes
      could help to prevent or postpone its onset by taking appropriate preventive
      measures, including the initiation of lifestyle changes. To date, early
      identification of prediabetes or type 2 diabetes has proven problematic, such
      that there is an urgent requirement for tools enabling easy, quick, and accurate
      diagnosis. AIM: To develop an easy, quick, and precise tool for diagnosing early
      diabetes based on machine learning algorithms. METHODS: The dataset used in this
      study was based on the health profiles of diabetic and non-diabetic patients from
      hospitals in India. A novel machine learning algorithm, termed "mixture of
      expert", was used for the determination of a patient's diabetic state. Out of a
      total of 1415 subjects, 1104 were used to train the mixture of expert system. The
      remaining 311 data sets were reserved for validation of the algorithm. Mixture of
      expert was implemented in matlab to train the data for the development of the
      model. The model with the minimum mean square error was selected and used for the
      validation of the results. RESULTS: Different combinations and numbers of hidden
      nodes and expectation maximization (EM) iterations were used to optimize the
      accuracy of the algorithm. The overall best accuracy of 99.36% was achieved with
      an iteration of 150 and 20 hidden nodes. Sensitivity, specificity, and total
      classification accuracy were calculated as 99.5%, 99.07%, and 99.36%,
      respectively. Furthermore, a graphical user interface was developed in java
      script such that the user can readily enter the variables and easily use the
      algorithm as a tool. CONCLUSIONS: This study describes a highly precise machine
      learning prediction tool for identifying prediabetic, diabetic, and non-diabetic
      individuals with high accuracy. The tool could be used for large scale screening
      in hopsitals or diabetes prevention programs.

PMID- 22972446
TI  - Preretinal partial pressure of oxygen gradients before and after experimental
      pars plana vitrectomy.
AB  - PURPOSE: To evaluate preretinal partial pressure of oxygen (PO2) gradients before
      and after experimental pars plana vitrectomy. METHODS: Arteriolar, venous, and
      intervascular preretinal PO2 gradients were recorded in 7 minipigs during slow
      withdrawal of oxygen-sensitive microelectrodes (10-MUm tip diameter) from the
      vitreoretinal interface to 2 mm into the vitreous cavity. Recordings were
      repeated after pars plana vitrectomy and balanced salt solution (BSS) intraocular
      perfusion. RESULTS: Arteriolar, venous, and intervascular preretinal PO2 at the
      vitreoretinal interface were 62.3 +/- 13.8, 22.5 +/- 3.3, and 17.0 +/- 7.5 mmHg,
      respectively, before vitrectomy; 97.7 +/- 19.9, 40.0 +/- 21.9, and 56.3 +/- 28.4
      mmHg, respectively, immediately after vitrectomy; and 59.0 +/- 27.4, 25.2 +/-
      3.0, and 21.5 +/- 4.5 mmHg, respectively, 21/2 hours after interruption of BSS
      perfusion. PO2 2 mm from the vitreoretinal interface was 28.4 +/- 3.6 mmHg before
      vitrectomy; 151.8 +/- 4.5 mmHg immediately after vitrectomy; and 34.8 +/- 4.1
      mmHg 21/2 hours after interruption of BSS perfusion. PO2 gradients were still
      present after vitrectomy, with the same patterns as before vitrectomy.
      CONCLUSION: Preretinal PO2 gradients are not eliminated after pars plana
      vitrectomy. During BSS perfusion, vitreous cavity PO2 is very high. Interruption
      of BSS perfusion evokes progressive equilibration of vitreous cavity PO2 with
      concomitant progressive return of preretinal PO2 gradients to their previtrectomy
      patterns. This indicates that preretinal diffusion of oxygen is not altered after
      vitrectomy. The beneficial effect of vitrectomy in ischemic retinal diseases or
      macular edema may be related to other mechanisms, such as increased oxygen
      convection currents or removal of growth factors and cytokines secreted in the
      vitreous.

PMID- 22972447
TI  - Reduction of vitreous contamination rate after 25-gauge vitrectomy by surface
      irrigation with 0.25% povidone-iodine.
AB  - PURPOSE: To examine whether repeated ocular surface irrigation with 0.25%
      povidone-iodine, which is highly bactericidal and nonoculotoxic, reduces
      bacterial contamination of the vitreous during 25-gauge vitrectomy. METHODS:
      Overall, 4,407 eyes undergoing 25-gauge vitrectomy were studied; of these, 2,801
      were irrigated with infusion fluid (group A) and 1,606 with 0.25% povidone-iodine
      (group B). In each group (A and B), 103 eyes were studied bacteriologically,
      using ocular surface fluid samples after placing lid speculum (S1), after
      operative field irrigation (S2), and in vitreous samples at the beginning (V1)
      and at the completion of vitrectomy (V2). RESULTS: Bacterial contamination rate
      in S1 did not differ significantly between the groups A (5.5%) and B (6.8%).
      However, the contamination rates in S2, V1, and V2 were apparently lower in group
      B (0%, 0%, and 0%, respectively) than in group A (2.0%, 1.0%, and 2.0%,
      respectively). Incidence of endophthalmitis was 0 of 2,801 eyes in group A and 0
      of 1,606 eyes in group B. CONCLUSION: In 25-gauge vitrectomy, repeated operative
      field irrigation with 0.25% povidone-iodine reduced bacterial contamination in
      vitreous to extremely low level.

PMID- 22972448
TI  - Score Study Report 12: Development of venous collaterals in the Score Study.
AB  - PURPOSE: To investigate the prevalence of venous collaterals after branch and
      central retinal vein occlusion, assess the association of venous collaterals with
      other clinical features (including visual acuity), and determine if treatment
      with intravitreal corticosteroids influences the development of new venous
      collaterals. METHODS: Review of data from two multicenter randomized clinical
      trials in the Standard of Care versus COrticosteroid for REtinal Vein Occlusion
      (SCORE) Study. RESULTS: Statistically significant associations of venous
      collaterals and visual acuity at baseline or at follow-up were not found.
      Treatment with intravitreal triamcinolone acetonide did not appear to influence
      the development of venous collaterals. CONCLUSION: In contrast to some previous
      reports, development of venous collaterals did not demonstrate an independent
      association with visual acuity in eyes with branch retinal vein occlusion or
      central retinal vein occlusion in the SCORE Study. Intravitreal steroid effects
      do not appear to influence the development of venous collaterals.

PMID- 22972449
TI  - Object affordance influences instruction span.
AB  - We measured memory span for assembly instructions involving objects with handles
      oriented to the left or right side. Right-handed participants remembered more
      instructions when objects' handles were spatially congruent with the hand used in
      forthcoming assembly actions. No such affordance-based memory benefit was found
      for left-handed participants. These results are discussed in terms of motor
      simulation as an embodied rehearsal mechanism.

PMID- 22972450
TI  - Factors leading to obstacle contact during adaptive locomotion.
AB  - During everyday life, healthy adults occasionally trip over an obstacle that they
      knew was there. These 'spontaneous' trips can provide insight into the
      circumstances leading to trips and falls. The goal of this study was to describe
      the errors in foot placement and/or foot elevation that resulted in a spontaneous
      contact with a fixed, visible obstacle in young, healthy adults. Fifteen subjects
      stepped over an obstacle (height set to 25 % leg length) placed in the middle of
      an 8 m walkway, up to 300 times. Three subjects never contacted the obstacle and
      12 subjects contacted the obstacle 1-4 times, totaling 24 contacts in 3,843
      trials (0.6 %). Most of the contacts (92 %) were with the trail limb. Minimum
      foot clearance of the trail limb (trail MFC) decreased linearly (average slope of
      -1 mm/trial) with repeated trials. The majority of subjects (70 %) continued the
      linear decrease of trail MFC until they contacted the obstacle. The remaining
      contacts resulted from an apparent misjudgment of foot placement and/or foot
      elevation. Following contact, trail MFC increased 75 % in the subsequent trials
      and remained elevated at least up to 30 trials post-contact, but the trajectory
      of the unperturbed lead limb did not change, further supporting the idea of
      independent control for the lead and trail limbs during obstacle crossing.
      Possible causes of the progressive decrease in trail MFC until obstacle contact
      are considered.

PMID- 22972451
TI  - Time dilation caused by static images with implied motion.
AB  - The present study examined whether implicit motion information from static images
      influences perceived duration of image presentation. In Experiments 1 and 2, we
      presented observers with images of a human and an animal character in running and
      standing postures. The results revealed that the perceived presentation duration
      of running images was longer than that of standing images. In Experiments 3 and
      4, we used abstract block-like images that imitated the human figures used in
      Experiment 1, presented with different instructions to change the observers'
      interpretations of the stimuli. We found that the perceived duration of the block
      image presented as a man running was longer than that of the image presented as a
      man standing still. However, this effect diminished when the participants were
      told the images were green onions (objects with no implied motion), suggesting
      that the effect of implied motion cannot be attributed to low-level visual
      differences. These results suggest that implied motion increases the perceived
      duration of image presentation. The potential involvement of higher-order motion
      processing and the mirror neuron system is discussed.

PMID- 22972452
TI  - Neck and shoulder function in patients treated for oral malignancies: a 1-year
      prospective cohort study.
AB  - BACKGROUND: Neck and shoulder complaints can be a direct result of a neck
      dissection. METHODS: Maximal active lateral flexion of the neck, forward flexion
      and abduction of the shoulder, and self-perceived function were determined in 145
      patients treated for oral cancer. RESULTS: No short-term influence of
      radiotherapy was found on measured range of motion and self-perceived neck and
      shoulder function (p > .05). One year after a bilateral neck dissection, patients
      showed deteriorated lateral flexion of the neck, whereas patients treated with a
      unilateral modified radical neck dissection still reported pain during neck
      movements. Maximal forward flexion of the shoulder recovered to the level of
      healthy controls, but maximal abduction was still reduced in all patients.
      CONCLUSIONS: Neck dissection, tumor site, and extensive reconstruction are
      related to deterioration of shoulder function shortly after intervention. Maximal
      active shoulder abduction was affected most.

PMID- 22972453
TI  - Advances in the investigation of obstructive jaundice.
AB  - The causes of obstructive jaundice are varied, and timely, accurate methods of
      investigation are essential to avoid the development of complications. Imaging,
      invasive or non-invasive, should be carefully selected depending on the suspected
      underlying pathology in order to determine the degree and level of obstruction
      along with tissue acquisition and staging where relevant. Several imaging
      techniques will also allow subsequent therapeutic interventions to be carried
      out. This article reviews advances in the investigation of obstructive jaundice,
      highlighting recent developments, many of which at present remain restricted to
      large centres of expertise, but are likely to become more widespread in use as
      research progresses and local experience continues to improve.

PMID- 22972454
TI  - [Chronic pain patients' readiness to change after multimodal treatment. Short-
      and long-term effects].
AB  - BACKGROUND: Patients' readiness to behavioural changes according to the
      transtheoretical model (TTM) and criteria of treatment outcome are positively
      associated and have in part already been confirmed. For a stable effect of
      therapeutic treatment, patients' readiness to change seems indispensable for an
      independent and active pain management. Thus, in addition to an enhanced quality
      of life, increasing patients' motivation is a declared objective of the treatment
      at Dresden's Comprehensive Pain Center. In this study, it was examined how the
      readiness to change develops in the course of and during the 2 years following
      the multimodal treatment program. Furthermore, associations between outcome
      criteria of the treatment and patients' readiness to change were explored.
      MATERIALS AND METHODS: The database constitutes 169 patients who took part in a 4
      week interdisciplinary, partially residential pain treatment. Beside the Freiburg
      Pain Stages questionnaire ("Frieburger Fragebogen - Stadien der Bewaltigung
      chronischer Schmerzen", FF-STABS), a comprehensive pain diagnostic inventory
      including the Pain Disability Index (PDI), the SF-36 questionnaire, and the
      Hospital Anxiety and Depression Scale (HADS) was completed at six different time
      points (beginning of treatment, end of treatment, booster session after 10 weeks,
      after 6, 12, and 24 months). The statistical analyses were performed with SPSS
      16.0 including nonparametric analyses and variance analyses. RESULTS: Significant
      differences in the level of readiness to change between the beginning of
      treatment and all follow-up measures were observed. The average patients'
      readiness to change was still higher after 2 years than at the first measurement.
      However, a differentiated consideration revealed a small portion of patients who
      showed no change or even a reduction of motivation. After an additional week
      (booster session), the stages of readiness to change remained stable,
      irrespective of the direction of the previous change. Regarding therapeutic
      outcome, significant short- and long-term improvements were evident. For single
      outcome parameters, positive associations with the stages of readiness to change
      were found. CONCLUSION: The results indicate that the outpatient pain management
      program favorably affects patients' motivation and general quality of life. This
      effect also seems to be stable over a long period of time. As not all patients
      show an improvement in stage of readiness to change, the question arises whether
      the reason of the differences might lie within the patients' and whether specific
      interventions for motivation might be useful to enhance motivation before
      starting treatment.

PMID- 22972455
TI  - Mitochondria: Getting together.

PMID- 22972456
TI  - Bacterial pathogenesis: E. coli claims the driving seat for cancer.

PMID- 22972457
TI  - Chromothripsis and cancer: causes and consequences of chromosome shattering.
AB  - Genomic alterations that lead to oncogene activation and tumour suppressor loss
      are important driving forces for cancer development. Although these changes can
      accumulate progressively during cancer evolution, recent studies have revealed
      that many cancer cells harbour chromosomes bearing tens to hundreds of clustered
      genome rearrangements. In this Review, we describe how this striking phenomenon,
      termed chromothripsis, is likely to arise through chromosome breakage and
      inaccurate reassembly. We also discuss the potential diagnostic, prognostic and
      therapeutic implications of chromothripsis in cancer.

PMID- 22972459
TI  - Standardized curcuminoid extract (Curcuma longa l.) decreases gene expression
      related to inflammation and interacts with associated microRNAs in human
      umbilical vein endothelial cells (HUVEC).
AB  - The anti-inflammatory effects of curcuminoids have been extensively investigated.
      However, few studies investigate the mechanistic involvement of microRNAs
      (miRNAs) in their activity. The objective of this study was to examine the
      protective effects of standardized curcuminoid extract (SCE) in vascular
      inflammation of human umbilical vein endothelial cells (HUVEC) and the potential
      involvement of miRNA-126 and miRNA-146a. Escherichia coli lipopolysacharides
      (LPS) were used to induce inflammation. LPS-challenge increased gene-expression
      of toll-like receptor-4 (TLR-4) and downstream genes IL-1 receptor-associated
      kinase 1 (IRAK-1) and tumor necrosis factor receptor-associated factor 6 (TRAF-6)
      up to 2.58-, 2.39-, and 3.73-fold, respectively, relative to DMSO-treated
      controls that were not challenged with LPS. LPS up-regulated TLR-4, IRAK-1, and
      TRAF-6 in SCE pretreated cells (5 mg L(-1)), only up to 0.69-, 1.28-, and 1.15
      fold, respectively. miRNA-146a can be up-regulated by transcription nuclear
      factor kappa B (NF-kappaB) and acts as a negative feedback loop regulator
      involving IRAK-1 and TRAF-6 downregulation. In this study, the down-regulation of
      NF-kappaB was accompanied by reduced miRNA-146a expression. LPS-challenge induced
      mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell
      adhesion molecule-1 (ICAM-1) up to 5.65- and 10.65-fold, respectively. SCE
      prevented this effect and increases of up to only 2.92- and 5.26-fold of DMSO
      treated controls not challenged with LPS were observed. miRNA-126 regulates
      endothelial expression of VCAM-1, but was not inversely correlated to the
      expression of its target gene VCAM-1 upon SCE treatment; therefore, miRNA-126
      does not appear to be involved in the down-regulation of VCAM-1. Overall,
      curcuminoids are confirmed to have anti-inflammatory properties in HUVEC;
      however, neither miRNA-146a nor miRNA-126 seem to be involved in the SCE-induced
      down-regulation of the NF-kappaB-target genes IRAK-1, TRAF-6, and VCAM-1.

PMID- 22972460
TI  - Tailoring of molecular planarity to reduce charge injection barrier for high
      performance small-molecule-based ternary memory device with low threshold
      voltage.
AB  - By introducing a coplanar fluorenone into the center of an azo molecule, the turn
      on voltages of the ternary memory devices are significantly decreased to lower
      than -2 V due to the improved crystallinity and the reduced charge injection
      barrier. The resulting low-power consumption devices will have great potential
      applications in high-performance chips for future portable nanoelectronic
      devices.

PMID- 22972461
TI  - Systemic sclerosis endothelial cells recruit and activate dermal fibroblasts by
      induction of a connective tissue growth factor (CCN2)/transforming growth factor
      beta-dependent mesenchymal-to-mesenchymal transition.
AB  - OBJECTIVE: Clinical evidence suggests that the vascular abnormalities of systemic
      sclerosis (SSc) precede the onset of fibrosis, but molecular cues accounting for
      a possible vascular connection of SSc fibrosis have been elusive, although they
      have been searched for intensively. Since we had previously shown that connective
      tissue growth factor (CCN2), endowed with fibroblast-oriented activities, was
      overexpressed by endothelial cells (ECs) from SSc patients, we undertook this
      study to investigate its role and mechanisms in fibroblast activation. METHODS:
      Normal fibroblasts were challenged with conditioned medium of normal
      microvascular ECs (MVECs) and MVECs obtained from SSc patients with the diffuse
      form of the disease. Fibroblast invasion was studied using the Boyden chamber
      Matrigel assay. Fibroblast activation was evaluated by Western blotting and
      immunofluorescence of alpha-smooth muscle actin (alpha-SMA), vimentin, and type I
      collagen. Matrix metalloproteinase (MMP) production was evaluated by zymography
      and reverse transcription-polymerase chain reaction. Signal transduction and
      activation of the small GTPases RhoA and Rac1 were studied by Western blotting.
      Inhibition of SSc MVEC conditioned medium-dependent fibroblast activation was
      obtained by anti-CCN2 antibodies and the transforming growth factor beta
      (TGFbeta) antagonist peptide p17. RESULTS: SSc MVEC CCN2 stimulated fibroblast
      activation and invasion. Such activities depended on CCN2-induced overexpression
      of TGFbeta and its type I, II, and III receptors combined with overproduction of
      MMP-2 and MMP-9 gelatinases. All of these effects were reversed by the TGFbeta
      antagonist peptide p17. Motility increase required Rac1 activation and RhoA
      inhibition and was inhibited by an MMP inhibitor. These features connoted a
      mesenchymal style of cell invasion. Since fibroblast activation also fostered
      overexpression of alpha-SMA, vimentin, and type I collagen, the CCN2-dependent
      increase in fibroblast activities recapitulated the characteristics of a
      mesenchymal-to-mesenchymal transition. CONCLUSION: SSc MVECs recruit and activate
      dermal fibroblasts by induction of a CCN2/TGFbeta-dependent mesenchymal-to
      mesenchymal transition.

PMID- 22972462
TI  - Total sialic acid profile in regressing and remodelling organs during the
      metamorphosis of marsh frog (Pelophylax ridibundus Pallas 1771).
AB  - This study aimed to investigate the functional relationship of sialic acid in
      regressing and remodelling organs such as the tail, small intestine and liver
      during the metamorphosis of Pelophylax ridibundus. For this purpose, four groups
      were composed according to developmental periods by considering Gosner's criteria
      (1964). Our findings showed that the sialic acid content of the larval tail has
      an opposite profile to cell death process. Although the sialic acid content of
      the small intestine and liver did not change evidently during metamorphosis, it
      increased after the completion of metamorphosis. Frog tail extensively exhibited
      cell death process and decreased proliferative activity and underwent complete
      degeneration during metamorphic climax. In spite of increased apoptotic index, a
      decreased sialic acid level in the tail tissues during climax can be the
      indication of a death cell removal process. However, the intestine and the liver
      included both cell death and proliferative process and remodelling in their adult
      forms. Thus, their sialic acid profiles during metamorphosis were different from
      the tail's profile. These data show that sialic acid may be an indicator of the
      presence of some cellular events during metamorphosis and that it can have
      different roles in the developmental process depending on the organ's fate
      throughout metamorphosis.

PMID- 22972463
TI  - Strain characterization of the Korean CWD cases in 2001 and 2004.
AB  - Chronic wasting disease (CWD) has been recognized as a naturally occurring prion
      disease in North American deer (Odocoileus species), Rocky Mountain elk (Cervus
      elaphus nelsoni) and moose (Alces alces). The disease was confirmed only in elk
      in the Republic of Korea in 2001, 2004 and 2005. Epidemiological investigations
      showed that CWD was introduced via importation of infected elk from Canada
      between 1994 and 1997. In spite of the increasing geographic distribution and
      host range of CWD, little is known about the prion strain (s) responsible for
      distinct outbreaks of the disease. We carried out strain characterization, using
      transgenic mice overexpressing elk prion protein, including clinical assessment,
      pathological examination and biochemical analyses, in brain tissues derived
      following primary through tertiary transmissions. The final incubation period was
      shortened to approximately 130 dpi due to adaptation. Biochemical profiles
      remained identical between passages. Lesion profiling in recipient mice brains
      showed similar patterns of vacuolation scores and intensity. It is clear that
      there were no biochemical or histopathological differences in Korean CWD cases in
      2001 and 2004, suggesting a single strain was responsible for the outbreaks.

PMID- 22972464
TI  - An autoradiogram of skeletal muscle from a pig raised on a farm within 20 km of
      the Fukushima Daiichi nuclear power plant.
AB  - We utilized autoradiography to visualize radioactive contamination in the
      skeletal muscles of a pig raised within 20 km of the Fukushima Daiichi nuclear
      power plant following the nuclear accident. The autoradiogram of control muscle
      showed relatively homogenous exposure. In contrast, the autoradiogram of affected
      muscle showed a heterogeneous and sporadically dense imaging pattern. Photo
      luminescence densities of the affected and control muscles were 3.89 +/- 0.67 and
      2.13 +/- 0.43 PSL/mm(2), respectively. This difference indicated that radioactive
      cesium was distributed in the skeletal muscle of the affected pig.

PMID- 22972465
TI  - Cloning and quantification of ferret serum amyloid A.
AB  - Serum amyloid A (SAA) is used as a biomarker for infections and inflammation in
      humans and veterinary medicine. We cloned ferret cDNA encoding SAA from the liver
      of a ferret via reverse transcription PCR (RT-PCR). The sequence of the cDNA
      clone revealed that ferret SAA has an open reading frame of 387 bp that encodes
      129 amino acids. The deduced amino acid sequence of ferret SAA has 96.1, 89.9,
      86.0, 83.8, 83.0, 73.8 and 65.3% similarity to the mink, dog, cat, cattle, horse,
      human and mouse SAA genes, respectively. Compared to human SAA, the deduced
      ferret SAA amino acid sequence had an insertion of an 8-amino acid fragment
      between amino acids 88 and 95. Recombinant ferret SAA (rfrSAA) was expressed
      using an Escherichia coli (E. coli) strain, BL21 Star. Using Western blot
      analysis, anti-SAA mAb provided with the multispecies SAA ELISA kit reacted with
      purified rfrSAA. A significant dose-response relationship was observed between
      the rfrSAA protein and a commercial multispecies SAA ELISA kit. In contrast,
      rfrSAA was not recognized with the antibodies included in a commercial human SAA
      ELISA kit. These results suggest that the structure of ferret SAA is
      antigenically similar to other domestic animal SAAs, and the multispecies ELISA
      kit allows for the detection and quantification of ferret SAA in vivo.

PMID- 22972466
TI  - Large-scale survey of mitochondrial D-loop of the red-crowned crane Grus
      japonensis in Hokkaido, Japan by convenient genotyping method.
AB  - The Red-crowned Crane, Grus japonensis, is an endangered species of crane that
      has two separate breeding populations, one in the Amur River basin (continental
      population) and the other in eastern or northern Hokkaido, Japan (island
      population). So far, only two haplotypes (Gj1 and Gj2) have been identified in
      the mitochondrial D-loop in island population, whereas seven haplotypes have been
      found in continental population (Gj3-Gj9). We developed a rapid and inexpensive
      method of extensive genotyping of D-loop haplotypes in Red-crowned Cranes, based
      on amplification refractory mutation system (ARMS) PCR assay. Two hundred and
      three cranes in eastern Hokkaido were studied with this method and supplemental
      DNA sequencing. Only two haplotypes, Gj1 and Gj2, were confirmed in eastern
      Hokkaido with Gj2 as a major haplotype. Additionally, only Gj2 was identified in
      twelve feathers from both sexes found in northern Hokkaido. These results suggest
      scarce genetic diversity in island population of Red-crowned Cranes in Hokkaido,
      Japan.

PMID- 22972467
TI  - Serum zinc levels and their relationship with diseases in racehorses.
AB  - Zinc is one of the essential microelements involved in the regulation of enzyme
      activity, as well as metabolism of nucleic acid and proteins. There have been few
      reports on equine serum zinc concentrations during the training period, and
      little is known about the relationship between zinc levels and diseases in
      horses. In this study, we measured serum zinc levels in healthy Thoroughbred
      racehorses, as well as in other horses, under general disease or training
      conditions. The reference value for serum zinc levels in Thoroughbred horses was
      41-79 MUg/dl. There were no differences in serum zinc levels due to sex or age.
      Significant decreases in serum zinc levels were observed after training, but
      serum zinc levels did not vary with intensity of sweating. Serum zinc levels were
      lower in horses clinically diagnosed as having shipping fever (36.3 +/- 2.7
      MUg/dl), fever (45.3 +/- 3.0 MUg/dl) and cellulitis (44.0 +/- 3.4 MUg/dl), as
      compared to control values (59.7 +/- 9.7 MUg/dl). They also tended to decrease in
      experimentally infected horses one day after inoculation. Changes in serum zinc
      levels reached nadir one day after surgical invasion, except for a horse that
      experienced complicating shock. These results suggest that zinc is a serological
      indicator of inflammatory status in Thoroughbred horses.

PMID- 22972468
TI  - Upregulation of superoxide dismutase activity in the intestinal tract mucosa of
      germ-free mice.
AB  - Superoxide dismutase (SOD) catalyzes the breakdown of superoxide into hydrogen
      peroxide and oxygen in the antioxidant defense system. We had reported that the
      SOD activities in the ceca of germ-free (GF) mice were significantly higher than
      those in conventional (CV) mice. In this study, we confirmed the location where
      SOD activity and protein expression increased in the ceca of GF mice. An
      immunohistochemical analysis and total SOD activity assay were conducted using
      the mucosa and other remaining tissues in the ceca. In addition to SOD activity
      in the ceca, 4 sites of intestinal (duodenal, jejunal, ileal and colonic) mucosae
      in GF mice were compared with those of CV mice. Total SOD activity in the cecal
      mucosa of GF mice was significantly higher than that in CV mice (P<0.01), and the
      intensity of CuZnSOD-positive cells in cecal mucosa was increased in all GF mice.
      Total and CuZnSOD activities in the duodenal, jejunal, ileal, cecal and colonic
      mucosae of GF mice were significantly higher than those in CV mice (P<0.05, or
      P<0.01). Furthermore, CuZnSOD mRNA showed similar tendencies with respect to
      these activities. Our results suggest for the first time that upregulation of SOD
      activity occurs in the entire intestinal mucosa of GF mice.

PMID- 22972470
TI  - Synthesis and biological evaluation of a 6-aminofuro[3,2-c]pyridin-3(2H)-one
      series of GPR 119 agonists.
AB  - G protein-coupled receptor 119 (GPCR 119 (GPR119)) agonists have received
      considerable attention as a promising therapeutic option for treatment of type 2
      diabetes mellitus. GPR119 is one of the GPCRs expressed in pancreatic islet beta
      cells and its activation enhances stimulation of insulin secretion in a glucose
      dependent manner. We have recently described a series of 6-amino-1H-indan-1-ones
      as potent, selective, and orally bioavailable GPR119 agonists with an amino group
      that plays important roles not only in their drug-like properties, such as high
      aqueous solubility, but also in their potent agonistic activity. However, many of
      these compounds displayed strong to moderate inhibition of human ether-a-go-go
      related gene channel. Attenuation of the basicity of the amino group by replacing
      the adjacent benzene ring with electron-deficient heteroaromatic rings provided
      several heterocyclic cores among which 6-aminofuro[3,2-c]pyridin-3(2H)-one was
      selected as a promising scaffold. Further optimization around the side chain
      moiety led to the discovery of 17i, which showed not only strong human GPR119
      agonistic activity (EC50=14 nM), but also beneficial effects on gastric emptying
      and plasma total glucagon-like peptide-1 levels in mice.

PMID- 22972469
TI  - Computational modelling of anti-angiogenic therapies based on multiparametric
      molecular imaging data.
AB  - Computational tumour models have emerged as powerful tools for the optimization
      of cancer therapies; ideally, these models should incorporate patient-specific
      imaging data indicative of therapeutic response. The purpose of this study was to
      develop a tumour modelling framework in order to simulate the therapeutic effects
      of anti-angiogenic agents based upon clinical molecular imaging data. The model
      was applied to positron emission tomography (PET) data of cellular proliferation
      and hypoxia from a phase I clinical trial of bevacizumab, an antibody that
      neutralizes the vascular endothelial growth factor (VEGF). When using pre-therapy
      PET data in combination with literature-based dose response parameters, simulated
      follow-up hypoxia data yielded good qualitative agreement with imaged hypoxia
      levels. Improving the quantitative agreement with follow-up hypoxia and
      proliferation PET data required tuning of the maximum vascular growth fraction
      (VGF(max)) and the tumour cell cycle time to patient-specific values. VGF(max)
      was found to be the most sensitive model parameter (CV = 22%). Assuming
      availability of patient-specific, intratumoural VEGF levels, we show how
      bevacizumab dose levels can potentially be 'tailored' to improve levels of tumour
      hypoxia while maintaining proliferative response, both of which are critically
      important in the context of combination therapy. Our results suggest that, upon
      further validation, the application of image-driven computational models may
      afford opportunities to optimize dosing regimens and combination therapies in a
      patient-specific manner.

PMID- 22972471
TI  - Inherited thrombocytopenias: the evolving spectrum.
AB  - The chapter of inherited thrombocytopenias has expanded greatly over the last
      decade and many "new" forms deriving from mutations in "new" genes have been
      identified. Nevertheless, nearly half of patients remain without a definite
      diagnosis because their illnesses have not yet been described. The diagnostic
      approach to these diseases can still take advantage of the algorithm proposed by
      the Italian Platelet Study Group in 2003, although an update is required to
      include the recently described disorders. So far, transfusions of platelet
      concentrates have represented the main tool for preventing or treating bleedings,
      while haematopoietic stem cell transplantation has been reserved for patients
      with very severe forms. However, recent disclosure that an oral thrombopoietin
      mimetic is effective in increasing platelet count in patients with MYH9-related
      thrombocytopenia opened new therapeutic perspectives. This review summarizes the
      general aspects of inherited thrombocytopenias and describes in more detail MYH9
      related diseases (encompassing four thrombocytopenias previously recognized as
      separate diseases) and the recently described ANKRD26-related thrombocytopenia,
      which are among the most frequent forms of inherited thrombocytopenia.

PMID- 22972472
TI  - An intronic variant associated with systemic lupus erythematosus changes the
      binding affinity of Yinyang1 to downregulate WDFY4.
AB  - Two recent genome-wide association studies of East Asian populations revealed
      three genetic variants in WDFY4/LRRC18 associated with systemic lupus
      erythematosus (SLE). To identify the gene contributing to this disease
      susceptibility, we examined the mRNA expression of WDFY4 and LRRC18 in patients
      with SLE and healthy controls. WDFY4 was significantly downregulated in SLE
      patients as compared with controls. We used allelic expression and dual
      luciferase assays to identify the functional variant. Transcriptional activity
      was lower for the rs877819A than -G allele. Electrophoretic mobility shift and
      supershift assays revealed that the transcription factor Yinyang1 (YY1) binds to
      rs877819, with lower affinity to the A allele, which explained the reduced
      transcriptional activity. This effect was further confirmed by YY1 small
      interfering RNA knockdown, overexpression and chromatin immunoprecipitation
      experiments. rs877819 in WDFY4 might be the functional site associated with SLE
      by reduced binding of YY1 and downregulating WDFY4 expression.

PMID- 22972473
TI  - Fine-mapping in African-American women confirms the importance of the 10p12 locus
      to sarcoidosis.
AB  - Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms.
      Genome-wide association studies in European populations have reported significant
      associations between sarcoidosis and single-nucleotide polymorphisms (SNPs)
      located in the intergenic region between the C10ORF67 and OTUD1 genes on
      chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine
      mapping at 10p12 and 10q22 to assess associations of genetic variants in these
      regions with sarcoidosis risk in African-American women, based on 486 sarcoidosis
      cases and 943 age- and geography-matched controls in a nested case-control study
      within the Black Women's Health Study. There were no significant associations
      with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67
      OTUD1 intergenic region revealed a strong inverse association of the variants
      rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). Both SNPs
      are located inside an ~300 kb low recombination region of chromosome 10p12,
      suggesting that both SNPs are tagging the same causal variant. Our top SNP
      (rs11013452) is located inside a smaller linkage disequilibrium block in HapMap
      YRI, further narrowing the position of the causal SNP to a region of ~8 kb on
      chromosome 10p12. The present findings confirm the potential importance of the
      10p12 locus in the etiology of sarcoidosis.

PMID- 22972474
TI  - Transcriptional signatures as a disease-specific and predictive inflammatory
      biomarker for type 1 diabetes.
AB  - The complex milieu of inflammatory mediators associated with many diseases is
      often too dilute to directly measure in the periphery, necessitating development
      of more sensitive measurements suitable for mechanistic studies, earlier
      diagnosis, guiding therapeutic decisions and monitoring interventions. We
      previously demonstrated that plasma samples from recent-onset type 1 diabetes (RO
      T1D) patients induce a proinflammatory transcriptional signature in freshly drawn
      peripheral blood mononuclear cells (PBMCs) relative to that of unrelated healthy
      controls (HC). Here, using cryopreserved PBMC, we analyzed larger RO T1D and HC
      cohorts, examined T1D progression in pre-onset samples, and compared the RO T1D
      signature to those associated with three disorders characterized by airway
      infection and inflammation. The RO T1D signature, consisting of interleukin-1
      cytokine family members, chemokines involved in immunocyte chemotaxis, immune
      receptors and signaling molecules, was detected during early pre-diabetes and
      found to resolve post-onset. The signatures associated with cystic fibrosis
      patients chronically infected with Pseudomonas aeruginosa, patients with
      confirmed bacterial pneumonia, and subjects with H1N1 influenza all reflected
      immunological activation, yet each were distinct from one another and negatively
      correlated with that of T1D. This study highlights the remarkable capacity of
      cells to serve as biosensors capable of sensitively and comprehensively
      differentiating immunological states.

PMID- 22972475
TI  - Heart rate reduction in heart failure: ivabradine or beta blockers?
AB  - Ivabradine, a selective I f current inhibitor, decreasing the heart rate in those
      with sinus rhythm, has been added to the most recent European guidelines on heart
      failure. It is indicated in addition to beta blockers in patients with decreased
      left ventricular ejection fraction and sinus rate of over 70 beats per minute.
      Several well-designed studies including the BEAUTIFUL and the SHIFT trials
      demonstrated clear benefits of ivabradine in symptomatic patients, both with
      angina and with heart failure, with left ventricular systolic dysfunction. The
      main objective of this review is to provide a comprehensive summary of data on
      ivabradine, and to discuss the potential role of this new agent in the spectrum
      of modern therapeutics for heart failure.

PMID- 22972476
TI  - Delivery of multiple transgenes to plant cells by an improved version of
      MultiRound Gateway technology.
AB  - At present, only few methods for the effective assembly of multigene constructs
      have been described. Here we present an improved version of the MultiRound
      Gateway technology, which facilitates plant multigene transformation. The system
      consists of two attL-flanked entry vectors, which contain an attR cassette, and a
      transformation-competent artificial chromosome based destination vector. By
      alternate use of the two entry vectors, multiple transgenes can be delivered
      sequentially into the Gateway-compatible destination vector. Multigene constructs
      that carried up to seven transgenes corresponding to more than 26 kb were
      assembled by seven rounds of LR recombination. The constructs were successfully
      transformed into tobacco plants and were stably inherited for at least two
      generations. Thus, our system represents a powerful, highly efficient tool for
      multigene plant transformation and may facilitate genetic engineering of
      agronomic traits or the assembly of genetic pathways for the production of
      biofuels, industrial or pharmaceutical compounds in plants.

PMID- 22972477
TI  - Gender non-specific efficacy of ZFN mediated gene targeting in pigs.

PMID- 22972479
TI  - Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the
      caspase- and mitochondria-dependent pathways.
AB  - Leukemia, one of the causes of cancer-related death in humans, is an aggressive
      malignancy via the rapid growth of abnormal white blood cells. The aim of this
      study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a
      mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra,
      has been proven to induce cytotoxic effects in many cancer cell lines. In the
      current study, we investigated the effects of GA in mouse leukemia cells in
      vitro. The results indicated that GA induced morphological changes, G0/G1 phase
      arrest, apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast
      microscopy, DAPI-staining, flow cytometry and comet assay. The results from the
      flow cytometric assay showed that GA increased ROS levels, reduced the
      mitochondrial membrane potential (DeltaPsim) and stimulated caspase-3 activity in
      WEHI-3 cells. GA regulated the intrinsic and extrinsic apoptosis-associated
      protein expression which was determined by western blotting. In addition,
      endoplasmic reticulum (ER) stress responses were observed in GA-treated WEHI-3
      cells. GA promoted the trafficking of apoptosis-inducing factor (AIF), cytochrome
      c and endonuclease G (Endo G) in WEHI-3 cells. Based on this evidence, GA
      triggered apoptosis occurs through the death receptor, mitochondria-mediated and
      ER stress multiple signaling pathways.

PMID- 22972478
TI  - Characterization of estrogen-responsive transgenic marine medaka Oryzias dancena
      germlines harboring red fluorescent protein gene under the control by endogenous
      choriogenin H promoter.
AB  - Transgenic marine medaka (Oryzias dancena) germlines were generated by the
      microinjection of the red fluorescent protein (RFP) reporter gene (rfp) driven by
      the endogenous choriogenin H gene (chgH) promoter. The selected transgenic lines
      contained multiple copies of the transgene (3-42 copies per cell) in their
      genomes. Although all the founders were mosaic, the transgene was stably
      transmitted from the F1 generation to all subsequent generations following a
      Mendelian pattern. Different transgenic lines showed different responsiveness to
      estradiol-17beta (E2) exposure at the mRNA and protein levels, and the expression
      efficiency was dependent upon the transgene copy number. The induction of RFP was
      significantly affected by the developmental stage of transgenic larvae: later
      stage larvae (older than 7 days post-hatching) showed higher sensitivity to E2
      exposure than earlier-stage larvae. The response of transgenic expression to E2
      was fairly dependent upon the E2 dose (200-3,200 ng/L) and exposure period (1-7
      days), according to both a microscopic examination of RFP intensity and a qRT-PCR
      assay. The transgenic marine medaka showed similar transgenic responses to E2
      under freshwater, brackish, and seawater conditions. In addition to E2, the
      transgenic RFP signal was also successfully induced during 1-week exposure to
      various other natural (1 MUg/L estrone and 10 MUg/L estriol) and synthetic
      (xeno)estrogens (0.1 MUg/L 17alpha-ethynylestradiol, 1 MUg/L diethylstilbestrol,
      and 10 mg/L bisphenol A). The efficiency of transgene expression varied greatly
      among the chemicals tested. The results of this study suggest that the chgH-rfp
      transgenic marine medaka species will be useful in the in vivo detection of
      waterborne estrogens under a wide range of salinity conditions.

PMID- 22972480
TI  - A phantom for verification of dwell position and time of a high dose rate
      brachytherapy source.
AB  - Accuracy of dwell position and reproducibility of dwell time are critical in high
      dose rate (HDR) brachytherapy. A phantom was designed to verify dwell position
      and dwell time reproducibility for an Ir-192 HDR stepping source using Computed
      Radiography (CR). The central part of the phantom, incorporating thin alternating
      strips of lead and acrylic, was used to measure dwell positions. The outer part
      of the phantom features recesses containing different absorber materials (lead,
      aluminium, acrylic and polystyrene foam), and was used for determining
      reproducibility of dwell times. Dwell position errors of < 1 mm were easily
      detectable using the phantom. The effect of bending a transfer tube was studied
      with this phantom and no change of clinical significance was observed when
      varying the curvature of the transfer tube in typical clinical scenarios. Changes
      of dwell time as low as 0.1 s, the minimum dwell time of the treatment unit,
      could be detected by choosing dwell times over the four materials that produce
      identical exposure at the CR detector.

PMID- 22972481
TI  - Measurement and effects of MOSKIN detectors on skin dose during high energy
      radiotherapy treatment.
AB  - During in vivo dosimetry for megavoltage X-ray beams, detectors such as diodes,
      Thermo luminescent dosimeters (TLD's) and MOSFET devices are placed on the
      patient's skin. This of course will affect the skin dose delivered during that
      fraction of the treatment. Whilst the overall impact on increasing skin dose
      would be minimal, little has been quantified concerning the level of increase in
      absorbed dose, in vivo dosimeters produce when placed in the beams path. To this
      extent, measurements have been made and analysis performed on dose changes caused
      by MOSKIN, MOSFET, skin dose detectors. Maximum increases in skin dose were
      measured as 15 % for 6 MV X-rays and 10 % for 10 MV X-rays at the active crystal
      of the MOSKIN device which is the thickest part of the detector. This is compared
      to 32 and 26 % for a standard 1 mm thick LiF TLD at 10 * 10 cm(2) field size for
      6 and 10 MV X-rays respectively. Radiochromic film, EBT2 has been shown to
      provide a high resolution 2 dimensional map of skin dose from these detectors and
      measures the effects of in vivo dosimeters used for radiotherapy dose assessment.

PMID- 22972482
TI  - Changes in lymphocyte and neutrophil function induced by a marathon race.
AB  - The aim of this study was to investigate the changes in lymphocyte and neutrophil
      selected functions before and after a marathon race. Fifteen professional
      athletes were recruited, and the following parameters were measured: plasma
      concentrations of IL-1ra, IL-6, IL-8, IL-10, TNF-alpha and C-reactive protein
      (CRP); neutrophil phagocytic capacity; cytokine production by neutrophils and
      lymphocytes and signs of neutrophil and lymphocyte death. The marathon race had
      no effect on CRP levels, but plasma concentrations of IL-6 and IL-1ra were
      increased. Although no effect was observed on the production of IL-6, IL1-ra, TNF
      alpha, IL-1beta and IL-8 by unstimulated or stimulated neutrophils, a decrease in
      neutrophil phagocytic activity was observed immediately following the marathon. A
      high percentage of neutrophils undergoing apoptosis was observed due to the
      intense training regimen, whereas the percentages of apoptotic neutrophils were
      reduced after the race. The production of IL-2, TNF-alpha, IL-1beta and IL-10 by
      lymphocytes was decreased by 50%-80%, and the percentage of apoptotic and
      necrotic lymphocytes was increased by 42% and fourfold, respectively, as a result
      of the race. In conclusion, the increase in plasma levels of IL-6, IL-8, IL-1ra
      and IL-10 after the race was not due to the production of the cytokines by
      neutrophils or lymphocytes. In fact, the marathon led to a decrease in lymphocyte
      and neutrophil function, and the diminished function was more pronounced in
      lymphocytes, indicating an impairment in acquired immunity.

PMID- 22972483
TI  - Intravenous administration of multi-walled carbon nanotubes affects the formation
      of atherosclerosis in Sprague-Dawley rats.
AB  - BACKGROUND: Carbon nanotubes (CNTs) have many potential applications, including
      as delivery systems for a variety of diagnostic or therapeutic agents. However,
      it has been suggested that exposure to carbon nano-materials may be a risk for
      the development of vascular diseases due to its impact on the vascular
      endothelium. MATERIALS AND METHODS: Male Sprague-Dawley rats (180-200 g) were
      used to generate an atherosclerosis (AS) model, and the effect of intravenous
      administration of multi-walled carbon nanotubes (MWCNTs) on AS was studied. To
      further understand the underlying mechanisms, the effects of exposure of human
      umbilical vascular endothelial cells (HUVECs) to MWCNTs were examined. RESULTS:
      Exposure to 200 MUg/kg MWCNTs aggravated AS in this model. In addition, exposure
      to 50, 100 and 200 MUg/kg MWCNTs increased the calcification of the aorta in the
      model. Short-term exposure also revealed that 200 MUg/kg MWCNTs injured the
      endothelium in the aorta. MWCNTs disrupted the endothelial tight junction and
      induced endothelial cell death. CONCLUSION: The results demonstrated that MWCNTs
      could induce structural and functional changes in the endothelium, probably
      through vascular endotheliocyte injury, which eventually affected the development
      of AS in SD rats.

PMID- 22972484
TI  - Flexible ureterorenoscopic management of upper tract pathologies.
AB  - The last decade flexible ureteroscopy has progressed from an awkward diagnostic
      procedure with limited visualization to a precise surgical intervention allowing
      access to the entire collecting system. In this review, we present the current
      status and future perspectives of the ureterorenoscopic management of
      urolithiasis and non-stone-related upper tract pathologies.

PMID- 22972485
TI  - Involvement of p53 and nuclear factor-kappaB signaling pathway for the induction
      of G1-phase cell cycle arrest of cholangiocarcinoma cell lines by isomorellin.
AB  - Cell cycle arrest is closely linked to apoptosis. Isomorellin-a caged xanthone
      isolated from Garcinia hanburyi-induced apoptosis in cholangiocarcinoma (CCA)
      cell lines. To elucidate potential anticancer mechanisms, we investigated the
      effects of isomorellin on the growth, cell cycle progression, cell cycle
      regulated protein expression and nuclear factor-kappa B (NF-kappaB) activation of
      KKU-100 and KKU-M156 CCA cell lines; using sulforhodamine B assay, flow cytometry
      and Western blot analysis. The growth of both CCA cell lines was significantly
      inhibited by isomorellin treatment in a time- and dose-dependent manner. The
      respective IC(50) value of isomorellin for KKU-100 cells was 6.2+/-0.13, 5.1+/
      0.11 and 3.5+/-0.25 uM at 24, 48 and 72 h. By comparison, the respective IC(50)
      value for KKU-M156 cells was 1.9+/-0.22, 1.7+/-0.14 and 1.5+/-0.14 uM at 24, 48
      and 72 h. The growth inhibition of CCA cells by isomorellin was through the G0/G1
      phase arrest mediated by inhibition of NF-kappaB activation, up-regulation of
      p53, p21 and p27 and down-regulation of cyclin D1, cyclin E, Cdk4 and Cdk2
      protein levels. Our research suggests that isomorellin induces cell cycle arrest
      and apoptosis in CCA cell lines through p53 and the NF-kappaB-signaling pathway.
      The growth inhibitory potential of isomorellin was comparable to that of gambogic
      acid. Isomorellin shows potential as a therapeutic agent against human
      cholangiocarcinoma.

PMID- 22972486
TI  - Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting
      neuroinflammation.
AB  - Stroke is the third leading cause of death in industrialized countries and the
      most important cause of acquired adult disability. Many evidences suggest that
      inflammation accounts for the progression of cerebral ischemic injury.
      Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain
      plants, has shown anti-inflammatory activity against diabetes and Alzheimer's
      disease. In this study, we tested whether arctigenin can protect middle cerebral
      artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with
      arctigenin or vehicle for 7 d before being subjected to transient occlusion of
      middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO
      for neurological deficit scoring. Furthermore, the mechanism of the anti
      inflammatory effect of arctigenin was investigated with a focus on inflammatory
      cells, proinflammatory cytokines, and transcriptional factors. Arctigenin
      significantly reduced cerebral infarction and improved neurological outcome.
      Arctigenin suppressed the activation of microglia and decreased the expression of
      interleukin (IL)- 1beta and tumor necrosis factor (TNF)-alpha. These results
      revealed that arctigenin has a promising therapeutic effect in ischemic stroke
      treatment through an anti-inflammatory mechanism.

PMID- 22972488
TI  - Primary prophylaxis with granulocyte colony-stimulating factor (GCSF) reduces the
      incidence of febrile neutropenia in patients with non-Hodgkin lymphoma (NHL)
      receiving CHOP chemotherapy treatment without adversely affecting their quality
      of life: cost-benefit and quality of life analysis.
AB  - PURPOSE: Treatment of non-Hodgkin lymphoma (NHL) with cyclophosphamide,
      vincristine, doxorubicin and prednisone (CHOP) is known to be associated with a
      significant risk of febrile neutropenia (FN) of up to 50% [Osby et al. 2003 Blood
      101(10): 3840-3848; Lyman and Delgado 2003 Cancer 98(11): 2402-2409]. This study
      sought to examine the impact of primary granulocyte colony-stimulating factor
      (GCSF) prophylaxis on the incidence of FN, quality of life and overall cost.
      METHODS: In this retrospective cohort study, a group of 65 consecutive patients
      who received CHOP chemotherapy for NHL between December 2006 and October 2009 was
      studied. Patients either received filgrastim (300 mcg, average of seven doses),
      pegylated filgrastim (6 mg, single dose), or no GCSF prophylaxis. In addition, 19
      patients were asked to complete Functional Assessment of Cancer Therapy: General
      quality-of-life questionnaires. RESULTS: Overall, patients who received primary
      GCSF prophylaxis had significantly fewer FN compared to those who did not (5 vs.
      60%, p < 0.0001; numbers needed to treat of 1.8; 95% confidence interval, 1.6
      2.9). Cost-benefit analysis showed that the GCSF prophylaxis was associated with
      only a small increase in direct financial cost ($238 NZD [US$189] more to give
      primary GCSF prophylaxis per patient vs. no prophylaxis). The quality of life
      assessment showed that the patients' quality of life scores were similar to the
      published data from the validation study population (466 patients with mixed
      cancers) for Functional Assessment of Cancer Therapy. CONCLUSIONS: Our study
      shows that primary GCSF prophylaxis is effective in preventing FN in patients
      receiving CHOP chemotherapy for NHL without adversely affecting their quality of
      life, and is cost effective.

PMID- 22972487
TI  - Qualitative research into the symptom experiences of adult cancer patients after
      treatments: a systematic review and meta-synthesis.
AB  - PURPOSE: This review paper aimed to draw together the findings of qualitative
      research into the symptom experience of adult cancer patients in order to develop
      a better understanding of symptom experiences following cancer treatment.
      METHODS: Systematic review and meta-synthesis techniques were used to identify,
      appraise and synthesise the relevant literature. RESULTS: A thematic account of
      shared symptom experiences reported across papers is presented. Four main themes
      are discussed: interaction with health services, changing relationships, changing
      self and coping. In addition the range of symptoms reported across qualitative
      cancer research is highlighted. CONCLUSIONS: Unexpected symptoms can have
      negative effects on patients who need to be better prepared for long-term symptom
      experiences. In addition, it is important to acknowledge that patients' symptom
      experiences do not happen in isolation and should be addressed holistically
      within the context of patients' lives.

PMID- 22972489
TI  - Are polymorphisms of the beta(3)-adrenoceptor gene associated with an altered
      bladder function?
AB  - AIMS: As the presence of a Trp64Arg polymorphism of the gene encoding the beta(3)
      adrenoceptor (B3AR) has been linked to the presence of overactive bladder, we
      investigated whether additional polymorphisms are detectable in this gene and
      explore their relationships parameters related to lower urinary tract function.
      METHODS: The coding region and adjacent stretches of the B3AR gene was sequenced
      in 91 patients. In total, 1015 patients from a single academic hospital were
      genotyped for the presence of two single nucleotide polymorphisms. Symptom scores
      and parameters from pressure-flow studies were analyzed relative to genotype in
      the B3AR gene. RESULTS: No frequent novel polymorphisms were detected in the
      coding region. Five polymorphisms were found in the non-coding region of the gene
      but were in complete linkage with the 64Arg allele. Out of 32 parameters
      including bladder compliance, only prostate size was weakly (44 vs. 39 mL) but
      significantly associated with the 64Arg allele, but was not mirrored by an
      association with prostate-specific antigen levels. CONCLUSIONS: Our data do not
      support the hypothesis that polymorphisms in the B3AR gene are associated with
      alterations of bladder function.

PMID- 22972490
TI  - Systematic review of resection of primary midgut carcinoid tumour in patients
      with unresectable liver metastases.
AB  - BACKGROUND: Surgery for small intestinal neuroendocrine tumours (SI-NETs) is
      limited by metastatic disease in most patients. However, resection of the primary
      lesion alone has been advocated in patients with unresectable liver metastases.
      The present systematic review investigated the value of surgical resection of the
      primary lesion in patients with unresectable metastatic disease. METHODS: MEDLINE
      was searched for studies reporting the outcome of patients with SI-NETs and
      unresectable liver metastases where there was an explicit comparison between
      resection of the primary lesion alone and no resection. The primary outcome was
      overall survival. Secondary outcomes were progression-free survival, treatment
      related mortality and relief of symptoms. RESULTS: Meta-analysis was not
      possible, but six studies were analysed qualitatively to highlight useful
      information. Possible confounders in these studies were the inclusion of patients
      with other primary tumour sites, unknown primary tumour or non-metastatic
      disease. Bearing in mind these limitations, there was a clear trend towards
      longer survival in patients who underwent surgical resection in all studies;
      their median overall survival ranged from 75 to 139 months compared with 50-88
      months in patients who did not have resection. The difference between the two
      groups was statistically significant in three studies. Data on symptomatic
      improvement were scarce and did not suggest a clear benefit of surgery. Surgery
      related mortality seemed low. CONCLUSION: Available data suggest a possible
      benefit of resection of the primary lesion in patients with unresectable liver
      metastases, but the studies have several limitations and the results should
      therefore be considered with caution.

PMID- 22972492
TI  - Plasma electrochemistry: development of a reference electrode material for high
      temperature plasma.
AB  - This report describes the development of a high temperature reference electrode
      material for gas phase electrochemistry investigations. The electrode is
      constructed by careful assessment of different metal/metal oxide materials and
      operational stability in flame electrolyte medium. This will enable reliable
      dynamic electrochemistry investigations into redox reactions at the solid/gas
      interface, free of any solvent defined potential window restrictions.

PMID- 22972491
TI  - Determination of prostaglandin profiles in lipopolysaccharide-challenged guinea
      pig spleen.
AB  - We previously reported that splenic extract from lipopolysaccharide (LPS)
      challenged guinea pigs inhibits the exaggerated febrile response of
      splenectomized guinea pigs, suggesting that the spleen generates an inhibitory
      factor. Earlier results indicate that the factor is a lipid. In an effort to
      identify this factor, lipid fractions, isolated from splenic extracts of control
      and LPS-challenged guinea pigs, were analyzed with emphasis on identifying and
      quantifying prostanoids, which according to current knowledge are the likely
      bioactive factors. Prostaglandins have been extensively implicated in central and
      peripheral thermoregulation, and thus these lipids were targeted for
      characterization in the spleen. Analysis was done on the splenic extracts using
      solid-phase extraction, analytical and preparative thin-layer chromatography
      (TLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS).
      Four prostaglandins (PGs, 6-keto-PGF(1alpha) , PGF(2alpha) , PGE(2) and PGD(2) )
      were identified and quantified. Our data shows that these PG levels are doubled
      in LPS-treated guinea pig spleen compared with the control group. The methods
      used in this investigation to characterize PG in the spleen offer significant
      advantages over immunoassays previously used to identify and quantify PG in the
      spleen and other biological tissues. These methods will be utilized in further
      research needed to definitively characterize the role of splenic-derived PG in
      modulation of the febrile response induced by LPS.

PMID- 22972493
TI  - Viral dose, radioiodide uptake, and delayed efflux in adenovirus-mediated NIS
      radiovirotherapy correlates with treatment efficacy.
AB  - We have constructed a prostate tumor-specific conditionally replicating
      adenovirus (CRAd), named Ad5PB_RSV-NIS, which expresses the human sodium iodine
      symporter (NIS) gene. LNCaP tumors were established in nude mice and infected
      with this CRAd to study tumor viral spread, NIS expression, and efficacy. Using
      quantitative PCR, we found a linear correlation between the viral dose and viral
      genome copy numbers recovered after tumor infection. Confocal microscopy showed a
      linear correlation between adenovirus density and NIS expression. Radioiodide
      uptake vs virus dose-response curves revealed that the dose response curve was
      not linear and displayed a lower threshold of detection at 10(7) vp (virus
      particles) and an upper plateau of uptake at 10(11) vp. The outcome of
      radiovirotherapy was highly dependent upon viral dose. At 10(10) vp, no
      significant differences were observed between virotherapy alone or
      radiovirotherapy. However, when radioiodide therapy was combined with virotherapy
      at a dose of 10(11) vp, significant improvement in survival was observed,
      indicating a relationship between viral dose-response uptake and the efficacy of
      radiovirotherapy. The reasons behind the differences in radioiodide therapy
      efficacy can be ascribed to more efficient viral tumor spread and a decrease in
      the rate of radioisotope efflux. Our results have important implications
      regarding the desirable and undesirable characteristics of vectors for clinical
      translation of virus-mediated NIS transfer therapy.

PMID- 22972494
TI  - Inhibition of TGF-beta signaling in genetically engineered tumor antigen-reactive
      T cells significantly enhances tumor treatment efficacy.
AB  - Transforming growth factor beta (TGF-beta) is a cytokine with complex biological
      functions that may involve tumor promotion or tumor suppression. It has been
      reported that multiple types of tumors secrete TGF-beta, which can inhibit tumor
      specific cellular immunity and may represent a major obstacle to the success of
      tumor immunotherapy. In this study, we sought to enhance tumor immunotherapy
      using genetically modified antigen-specific T cells by interfering with TGF-beta
      signaling. We constructed three gamma-retroviral vectors, one that expressed TGF
      beta-dominant-negative receptor II (DNRII) or two that secreted soluble TGF-beta
      receptors: soluble TGF-beta receptor II (sRII) and the sRII fused with mouse IgG
      Fc domain (sRIIFc). We demonstrated that T cells genetically modified with these
      viral vectors were resistant to exogenous TGF-beta-induced smad-2 phosphorylation
      in vitro. The functionality of antigen-specific T cells engineered to resist TGF
      beta signaling was further evaluated in vivo using the B16 melanoma tumor model.
      Antigen-specific CD8+ T cells (pmel-1) or CD4+ T cells (tyrosinase-related
      protein-1) expressing DNRII dramatically improved tumor treatment efficacy. There
      was no enhancement in the B16 tumor treatment using cells secreting soluble
      receptors. Our data support the potential application of the blockade of TGF-beta
      signaling in tumor-specific T cells for cancer immunotherapy.

PMID- 22972495
TI  - Interventions to address chronic disease and HIV: strategies to promote smoking
      cessation among HIV-infected individuals.
AB  - Tobacco use, especially cigarette smoking, is higher than average in persons
      living with HIV/AIDS (PLWHA). The Public Health Service Clinical Practice
      Guideline for Treating Tobacco Use and Dependence states that, during every
      medical encounter, all smokers should be offered smoking cessation counseling,
      along with approved medications. The Guideline also recognizes PLWHA as a
      priority population, given the scarcity of research on effective cessation
      treatments in this group. The scant evidence suggests that conventional
      treatments, though worthwhile, are not as successful as might be hoped for. The
      reasons for this are not entirely clear, but may have to do with the complex
      array of medical and psychosocial factors that complicate their lives. Clinicians
      should consider re-treatment strategies for those patients who encounter
      difficulty when quitting smoking with conventional approaches, switching or
      augmenting treatments as needed to minimize adverse experiences, and to maximize
      tolerability, adherence, and cessation outcomes.

PMID- 22972496
TI  - Quantitative assessment of the association between GSTM1 null genotype and
      laryngeal cancer risk.
AB  - Previous studies investigating the association between glutathione S-transferase
      M1 (GSTM1) null genotype and laryngeal cancer risk reported controversial
      results. Thus, a meta-analysis was performed to clarify the effect of GSTM1 null
      genotype on laryngeal cancer risk. A literature search was performed for all
      possible studies. We estimated summary odd ratio (OR) with its 95 % confidence
      interval (95 % CI) to assess the association. Subgroup analyses were performed by
      ethnicity or the sample size. 24 individual case-control studies involving a
      total of 2,809 laryngeal cancer cases and 4,478 controls were finally included
      into this meta-analysis. Meta-analyses of total 24 studies showed the GSTM1 null
      genotype was significantly associated with increased laryngeal cancer risk
      (random-effects OR = 1.44, 95 % CI 1.19-1.73, P < 0.001). Subgroup analyses by
      ethnicity showed that the GSTM1 null genotype was associated with increased
      laryngeal cancer risk in both Caucasians (fixed-effects OR = 1.17, 95 % CI 1.04
      1.33, P = 0.012) and Asians (random-effects OR = 1.89, 95 % CI 1.28-2.77, P =
      0.001). Also, subgroup analyses by sample size also further identified this
      association above. The cumulative meta-analyses showed a trend of more obvious
      association between GSTM1 null genotype and increased risk of laryngeal cancer as
      information accumulated by year. Meta-analysis of available data suggests that
      GSTM1 null genotype contributes to increased laryngeal cancer risk in both
      Caucasians and East Asians.

PMID- 22972498
TI  - TOPORS modulates H2AX discriminating genotoxic stresses.
AB  - H2AX plays an important role in chromatin reorganization implicated in DNA repair
      and apoptosis under various DNA damaging conditions. In this study, the
      interaction between TOPORS (topoisomerase I-binding protein) and H2AX was
      verified using mammalian cell extracts exposed to diverse DNA damaging stresses
      such as ionizing radiation, doxorubicin, camptothecin, and hydrogen peroxide. In
      vitro assays for ubiquitination revealed that TOPORS functions as a novel E3
      ligase for H2AX ubiquitination. TOPORS was found to be dissociated from H2AX
      proteins when cells were exposed to oxidative stress, but not replication
      inducing DNA damaging stress. The protein stability of H2AX was decreased when
      TOPORS was ectopically expressed in cells, and oxidative stresses such as
      hydrogen peroxide and ionizing radiation induced recovery of the H2AX protein
      level. Therefore, these biochemical data suggest that TOPORS plays a key role in
      the turnover of H2AX protein, discriminating the type of DNA damaging stress.

PMID- 22972497
TI  - Post-therapeutic surveillance strategies in head and neck squamous cell
      carcinoma.
AB  - The management of head and neck squamous cell carcinomas does not end with the
      completion of ablative therapy. The oncologic objectives of post-treatment follow
      up are to detect recurrences and second primary tumors; beyond that, follow-up
      should evaluate acute and chronic treatment-related side effects, guide the
      rehabilitation process, alleviate functional loss, manage pain, restore
      nutritional status and assess psychosocial factors. In this structured review, we
      address the questions of timing and the tools required to achieve a complete and
      coherent routine surveillance. Several guidelines and consensus statements
      recommend clinical examination as the cornerstone of follow-up which should be
      performed for at least 5 years, although there are no data in favor of any one
      particular follow-up program, and only low-level evidence suggests an improvement
      in oncologic outcomes by close follow-up. Baseline imaging (computed tomography
      and magnetic resonance imaging) should be obtained within 2-6 months after
      definitive therapy if used for treatment response evaluation. Metabolic response,
      if indicated, should be assessed preferably after 3 months in patients who
      undergo curative-intent therapy with (chemo)-radiotherapy. Chest computed
      tomography is more sensitive than plain radiography, if used in follow-up, but
      the benefit and cost-effectiveness of routine chest computed tomography has not
      been demonstrated. There are no current data supporting modifications specific to
      the surveillance plan of patients with human papillomavirus-associated disease.

PMID- 22972500
TI  - Using the prevent-teach-reinforce model with families of young children with ASD.
AB  - This study was conducted to examine the feasibility and potential efficacy of
      implementing an adapted, family-centered version of the school-based prevent
      teach-reinforce (PTR) model. The research included two families who implemented
      the PTR process for their children in collaboration with the researchers. The
      adapted PTR was tested using a multiple baseline design across routines to
      examine changes in child behavior across experimental conditions. Results
      indicated that the adapted PTR intervention was associated with reduction in
      child problem behavior and increases in alternative behavior in both target and
      non-target routines. The results also indicated that the parents were able to
      implement the behavior intervention plan with fidelity and successfully use the
      PTR process for a novel routine. The PTR intervention also had high social
      validity ratings; both self- and novel-rated validity indicated that the PTR
      intervention was acceptable to both families and the community at large. The data
      are discussed in terms of the expanding evidence related to the PTR model and the
      extension to a family context.

PMID- 22972499
TI  - Identification of E2F target genes that are rate limiting for dE2F1-dependent
      cell proliferation.
AB  - BACKGROUND: Microarray studies have shown that the E2F transcription factor
      influences the expression of many genes but it is unclear how many of these
      targets are important for E2F-mediated control of cell proliferation. RESULTS: We
      assembled a collection of mutant alleles of 44 dE2F1-dependent genes and tested
      whether these could modify visible phenotypes caused by the tissue-specific
      depletion of dE2F1. More than half of the mutant alleles dominantly enhanced
      de2f1-dsRNA phenotypes suggesting that the in vivo functions of dE2F1 can be
      limited by the reduction in the level of expression of many different targets.
      Unexpectedly, several mutant alleles suppressed de2f1-dsRNA phenotypes. One of
      the strongest of these suppressors was Orc5. Depletion of ORC5 increased
      proliferation in cells with reduced dE2F1 and specifically elevated the
      expression of dE2F1-regulated genes. Importantly, these effects were independent
      of dE2F1 protein levels, suggesting that reducing the level of ORC5 did not
      interfere with the general targeting of dE2F1. CONCLUSIONS: We propose that the
      interaction between ORC5 and dE2F1 may reflect a feedback mechanism between
      replication initiation proteins and dE2F1 that ensures that proliferating cells
      maintain a robust level of replication proteins for the next cell cycle.

PMID- 22972501
TI  - The use of the autism diagnostic interview-revised with a latino population of
      adolescents and adults with autism.
AB  - Research shows that Latinos are less likely to be diagnosed with autism than
      their non-Latino counterparts. One factor that may contribute to these
      differences is that autism diagnostic instruments have not been adapted for the
      Latino population. The present study compared scores from the Autism Diagnostic
      Interview-Revised for two groups: 48 Latino adolescents and adults with autism
      and a matched sample of 96 non-Latino Whites. There were no significant
      differences between the two groups in total impairments in social reciprocity or
      communication. However, lower levels of restrictive-and-repetitive behaviors were
      found among Latino adolescents and adults with autism compared to Whites.
      Findings suggest that there may be cultural equivalency in some domains, but
      others may warrant further exploration.

PMID- 22972502
TI  - Oncologic and functional outcome of the preserved eye in malignant sinonasal
      tumors.
AB  - BACKGROUND: The purpose of this study was to analyze the oncologic and functional
      outcomes of the preserved eye in malignant sinonasal tumors with orbital
      involvement. METHODS: In a retrospective study of 19 consecutive patients who
      underwent craniofacial resection or maxillectomy with preservation of orbital
      contents and adjuvant radiotherapy, the oncological outcome in terms of local
      recurrence and survival was analyzed. The functional outcome in the preserved eye
      was analyzed for the cases that did not recur in the orbit. RESULTS: Nineteen
      patients were analyzed for their oncologic and functional outcomes. Fifteen
      patients underwent immediate reconstruction of the orbital support. Eight
      patients had local recurrences; 11 patients were disease free at the end of the
      follow-up. Squamous cell carcinoma has a high propensity for local recurrences
      (ie, 5 of 8 local recurrences were squamous cell carcinoma). Sixteen patients, in
      whom a satisfactory orbital tumor clearance was obtained, remained recurrence
      free in the orbit. All the preserved eyes retained adequate function after
      adjuvant radiotherapy. CONCLUSIONS: Adequate local control with preserved visual
      function can be obtained with surgery and adjuvant radiation in appropriately
      selected malignant sinonasal tumors with orbital involvement. The preserved eye,
      if reconstructed appropriately, maintains good overall function with acceptable
      morbidity.

PMID- 22972503
TI  - Expression of the molecular chaperone alphaB-crystallin in infiltrating ductal
      breast carcinomas and the significance thereof: an immunohistochemical and
      proteomics-based strategy.
AB  - This study aims to evaluate alphaB-crystallin expression in infiltrating ductal
      breast carcinomas (IDCAs), as well as, its prognostic significance. Using a two
      dimensional electrophoresis matrix-assisted laser desorption/ionisation-time of
      flight mass spectrometry investigation coupled to an immunohistochemical
      approach, we have assessed the expression of alphaB-crystallin in IDCAs, as well
      as, in other types of breast tumors (invasive lobular carcinomas, medullary
      carcinomas, and in situ ductal carcinomas). Correlation between alphaB-crystallin
      expression and clinicopathological parameters of breast cancer has also been
      investigated. Proteomic analyses revealed an increased expression of alphaB
      crystallin in IDCA tumors compared to adjacent nontumor tissues. Overexpression
      of this molecular chaperone was further confirmed in 51 tumor specimens.
      Statistical analyses revealed, however, no significant correlations between
      alphaB-crystallin expression and clinicopathological parameters of the disease
      (tumor stage, patient age, hormone receptors, SBR grade, and lymph node
      metastases). This study demonstrates the upregulation of alphaB-crystallin in
      IDCA tissues which may highlight its possible involvement in breast cancer
      development. Our findings do not, however, support the involvement of this
      molecular chaperone in the progression of this disease.

PMID- 22972504
TI  - A functional NQO1 609C>T polymorphism and risk of hepatocellular carcinoma in a
      Chinese population.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that
      catalyzes the two-electron reduction of quinoid compounds into hydroquinones,
      thus protecting cells from oxidative damage. A single base substitution (C->T)
      polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Thus,
      the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism
      (rs1800566) may play a pivotal role in tumor development. We hypothesized that a
      genetic variant in NQO1 may modify individual susceptibility to hepatocellular
      carcinoma (HCC). To test this hypothesis that the variant may play a role in HCC
      susceptibility, we conducted a hospital-based case-control study of 476 HCC
      patients and 526 cancer-free controls in a Chinese population. The matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry method was
      performed to detect the polymorphism. The results showed that the variant alleles
      and genotypes of NQO1 C609T were more common among cases than those among
      controls (P = 0.003 and P = 0.024). Compared with the NQO1 609CC genotype, there
      was a significantly greater risk of HCC associated with the variant NQO1 609TT
      [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI) = 1.12-2.28] and
      combined NQO1 609TC/TT (adjusted OR = 1.37, 95 % CI = 1.04-1.80) genotypes.
      Moreover, when subgroup analyses were performed, we found that the increase in
      risk was more evident among younger subjects, men, HbsAg-positive individuals,
      never smokers, never drinkers, and subjects without family history of cancer.
      These results suggest that the presence of the NQO1 C609T polymorphism may be a
      marker of genetic susceptibility to HCC.

PMID- 22972505
TI  - Association of human herpes, papilloma and polyoma virus families with bladder
      cancer.
AB  - The aim of the present study was to assess the possible etiologic role of human
      papillomavirus (HPV), human herpes virus (HHV) and the human polyoma virus
      families (BKV and JCV) in the tumourigenesis of bladder cancer. Thirty biopsy
      specimens from patients with different grades and stages of bladder cancer, who
      underwent transurethral bladder cancer resection, and 30 normal bladder mucosa
      specimens were analysed using polymerase chain reaction (PCR) for the detection
      of the above three virus family members. The presence of HPV was determined in
      all specimens with nested PCR and real-time quantitative PCR. All cancerous
      specimens, including the control group, were found to be negative both by PCR and
      real-time qPCR for the presence of HPV DNA, whilst all samples examined by PCR
      tested negative for the presence of HSV-1,2 Varicella zoster virus and HSV-7 DNA.
      Cytomegalovirus, HHV-6 and HHV-8 exhibited similar incidence in sample positivity
      in both cancerous and healthy tissues. EBV showed a higher prevalence in bladder
      cancer specimens compared to healthy tissue (p = 0.048), whilst BKV and JCV were
      detected only in tumour samples. The presence of EBV in a significant proportion
      of bladder tumours indicates the etiological role of this virus in cancer
      tumourigenesis.

PMID- 22972506
TI  - Preoperative axillary ultrasound and fine-needle aspiration biopsy in the
      diagnosis of axillary metastases in patients with breast cancer: predictors of
      accuracy and future implications.
AB  - BACKGROUND: The utility of axillary lymph node dissection after sentinel lymph
      node biopsy has been called into question. We sought to determine the
      sensitivity, specificity, and accuracy of axillary ultrasound and fine-needle
      aspiration biopsy (FNAB) in the identification of axillary nodal metastasis in
      early breast cancer patients. METHODS: Data of patients with stage I and II
      breast cancer who underwent surgery and staging were reviewed. Axillary
      ultrasound findings were assessed and lymph node status recorded after axillary
      dissection. The data were cross-tabulated, and test characteristics were
      calculated. RESULTS: Of 235 patients, none demonstrated more than 2 positive
      sentinel lymph nodes. Ductal carcinoma was present in 68%, estrogen and
      progesterone receptors were positive in 81 and 64%, respectively, Her-2/neu was
      positive in 10%, and 36% were axillary node positive. The sensitivity and
      specificity of ultrasound alone were 55 and 88%, respectively. Predictors of
      abnormal ultrasound included size of metastasis, estrogen receptor and Her-2
      status, tumor grade, and presence of lymphovascular invasion. Addition of FNAB
      increased the sensitivity and specificity to 69 and 100%. In conjunction with
      FNAB, the positive and negative predictive values were 100 and 54%, respectively.
      Ten percent of patients with nodal metastases demonstrated a positive FNAB.
      Patients with a positive FNAB did not harbor more nodal metastases or a greater
      proportion of gross extranodal disease compared to patients not subjected to
      FNAB. CONCLUSIONS: Axillary ultrasound with FNAB has an accuracy of >70% in this
      series. It is easily performed and may avoid unnecessary sentinel lymph node
      biopsy in a significant number of patients.

PMID- 22972507
TI  - Management and recurrence patterns of desmoids tumors: a multi-institutional
      analysis of 211 patients.
AB  - BACKGROUND: Desmoid tumors are rare soft-tissue neoplasms with limited data on
      their management. We sought to determine the rates of recurrence following
      surgery for desmoid tumors and identify factors predictive of disease-free
      survival. METHODS: Between January 1983 and December 2011, 211 patients with
      desmoid tumors were identified from three major surgical centers.
      Clinicopathologic and treatment characteristics were analyzed to identify
      predictors of recurrence. RESULTS: Median age was 36 years; patients were
      predominantly female (68 %). Desmoid tumors most commonly arose in extremities
      (32 %), abdominal cavity (23 %) or wall (21 %), and thorax (15 %); median size
      was 7.5 cm. Most patients had an R0 surgical margin (60 %). The 1- and 5-year
      recurrence-free survival was 81.3 and 52.8 %, respectively. Factors associated
      with worse recurrence-free survival were: younger age (for each 5-year increase
      in age, hazard ratio [HR] = 0.90, 95 % confidence interval [95 % CI] 0.82-0.98)
      and extra-abdominal tumor location (abdominal wall referent: extra-abdominal
      site, HR = 3.28, 95 % CI, 1.46-7.36) (both P < 0.05). CONCLUSIONS: Recurrence
      remains a problem following resection of desmoid tumors with as many as 50 % of
      patients experiencing a recurrence within 5 years. Factors associated with
      recurrence included age, tumor location, and margin status. While surgical
      resection remains central to the management of patients with desmoid tumors, the
      high rate of recurrence highlights the need for more effective adjuvant
      therapies.

PMID- 22972508
TI  - Multifocality and total tumor diameter predict central neck lymph node metastases
      in papillary thyroid microcarcinoma.
AB  - PURPOSE: To identify the subgroup of high-risk papillary thyroid microcarcinoma
      (PTMC) inclined to lymph node metastasis (LNM). METHODS: Patients who underwent
      total thyroidectomy with central neck dissection and had a pathologic diagnosis
      of PTMC between 2003 and 2010 at Wuhan Union Hospital were identified. The
      frequency of LNM was retrospectively analyzed according to the
      clinicopathological features. For multifocal lesions, total tumor diameter (TTD)
      was calculated as the sum of the maximal diameter of each lesion. Last, a meta
      analysis was performed with respect to multifocality and LNM in the PTMCs.
      RESULTS: The proportion of LNM was similar between multifocal PTMCs with TTD <= 1
      cm and unifocal tumors with diameter <= 1 cm (37.5 vs. 30%, P = 0.463). LNM
      frequency was also similar between multifocal PTMCs with 1 < TTD <= 2 cm (TTD
      greater than 1 cm but less than or equal to 2 cm) and unifocal tumors with 1 <
      diameter <= 2 cm (56.8 vs. 64.9%, P = 0.330). However, LNM frequency was
      significantly higher in multifocal PTMCs with TTD > 1 cm than unifocal tumors
      with diameter <= 1 cm (60.4 vs. 30%, P < 0.001). A meta-analysis of nine
      publications plus our own data with a total 1,586 PTMCs demonstrated that
      multifocality was significantly associated with LNM risk (odds ratio 1.9, 95%
      confidence interval 1.5-2.4). CONCLUSIONS: Multifocal PTMC with TTD > 1 cm has a
      similar risk of LNM as a clinical papillary cancer. Routine central neck
      dissection is recommended in this subgroup of patients.

PMID- 22972509
TI  - Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle
      after ischaemic injury.
AB  - Biomaterial-guided regeneration represents a novel approach for the treatment of
      myopathies. Revascularisation and the intramuscular extracellular matrix are
      important factors in stimulating myogenesis and regenerating muscle damaged by
      ischaemia. In this study, we used an injectable collagen matrix, enhanced with
      sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration.
      The elastic properties of collagen and sLeX-collagen matrices were similar to
      those of skeletal muscle, and culture of pluripotent mESCs on the matrices
      promoted their differentiation into myocyte-like cells expressing Pax3, MHC3,
      myogenin and Myf5. The regenerative properties of matrices were evaluated in
      ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the
      production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and
      IGF binding protein-2 and -5 after 3 days. This was followed by muscle
      regeneration, including a greater number of regenerating myofibres and increased
      transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days.
      Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment
      of bone marrow-derived progenitor cells, the development of larger arterioles and
      the restoration of tissue perfusion. Both matrix treatments tended to reduce
      maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of
      force and also prevented muscle fatigue. Only sLeX-matrix treatment improved
      mobility of mice on a treadmill. Together, these results suggest a novel approach
      for regenerative myogenesis, whereby treatment only with a matrix, which
      possesses an inherent ability to guide myogenic differentiation of pluripotent
      stem cells, can enhance the endogenous vascular and myogenic regeneration of
      skeletal muscle, thus holding promise for future clinical use.

PMID- 22972511
TI  - Soft-tissue damage and segmental instability in adult patients with cervical
      spinal cord injury without major bone injury.
AB  - STUDY DESIGN: A retrospective imaging and clinical study. OBJECTIVE: To evaluate
      the extraneural soft-tissue damage and its clinical relevance in patients with
      traumatic cervical spinal cord injury (SCI) without major bone injury. SUMMARY OF
      BACKGROUND DATA: To date, various kinds of cervical discoligamentous injuries
      have been demonstrated on magnetic resonance images in patients with SCI without
      bony injury. However, it has not been clear whether these magnetic resonance
      imaging abnormalities are actually related to spinal segmental instability and
      the patients' neurological status. METHODS: Eighty-eight adult patients with
      acute traumatic cervical SCI without major bone injury were examined by flexion
      extension lateral radiographs and magnetic resonance images within 2 days after
      trauma. We excluded patients with flexion recoil injury; therefore, most of the
      patients included were considered to have sustained a hyperextension injury.
      Instability of the injured cervical segment was defined when there was more than
      3.5-mm posterior translation and/or more than a 11 degrees  difference in the
      intervertebral angle between the site of interest and adjacent segments. The
      neurological status was evaluated according to the American Spinal Injury
      Association motor score. RESULTS: On magnetic resonance images, the damage to the
      anterior longitudinal ligament and intervertebral disc were apparent in 44 and 37
      patients, respectively. Various degrees of prevertebral fluid collection
      (prevertebral hyperintensity) were demonstrated in 76 patients. These magnetic
      resonance imaging abnormalities were significantly associated with initial
      cervical segmental instability as judged by flexion-extension radiographs.
      Interestingly, the American Spinal Injury Association motor score had a
      significant association with either magnetic resonance imaging abnormalities or
      segmental instability but not with the cervical canal diameter. CONCLUSION: A
      considerable proportion of the patients with traumatic cervical SCI without major
      bone injury were shown to have various types of soft-tissue damage associated
      with cervical segmental instability at the early stages of the injury. The
      severity of paralysis greatly depended on these discoligamentous injuries.

PMID- 22972510
TI  - Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte
      apoptosis through activation of beta-catenin.
AB  - It is a widely held belief that the sole effect of muscle on bone is through
      mechanical loading. However, as the two tissues are intimately associated, we
      hypothesized that muscle myokines may have positive effects on bone. We found
      that factors produced by muscle will protect osteocytes from undergoing cell
      death induced by dexamethasone (dex), a glucocorticoid known to induce osteocyte
      apoptosis thereby compromising their capacity to regulate bone remodeling. Both
      the trypan blue exclusion assay for cell death and nuclear fragmentation assay
      for apoptosis were used. MLO-Y4 osteocytes, primary osteocytes, and MC3T3
      osteoblastic cells were protected against dex-induced apoptosis by C2C12 myotube
      conditioned media (MT-CM) or by CM from ex vivo electrically stimulated, intact
      extensor digitorum longus (EDL) or soleus muscle derived from 4 month-old mice.
      C2C12 MT-CM, but not undifferentiated myoblast CM prevented dex-induced cell
      apoptosis and was potent down to 0.1 % CM. The CM from EDL muscle electrically
      stimulated tetanically at 80 Hz was more potent (10 fold) in prevention of dex
      induced osteocyte death than CM from soleus muscle stimulated at the same
      frequency or CM from EDL stimulated at 1 Hz. This suggests that electrical
      stimulation increases production of factors that preserve osteocyte viability and
      that type II fibers are greater producers than type I fibers. The muscle
      factor(s) appears to protect osteocytes from cell death through activation of the
      Wnt/beta-catenin pathway, as MT-CM induces beta-catenin nuclear translocation and
      beta-catenin siRNA abrogated the positive effects of MT-CM on dex-induced
      apoptosis. We conclude that muscle cells naturally secrete factor(s) that
      preserve osteocyte viability.

PMID- 22972512
TI  - Upregulation of T-type Ca2+ channels in primary sensory neurons in spinal nerve
      injury.
AB  - STUDY DESIGN: Painful behavior testing, whole-cell patch clamp recordings, and
      PCR analysis were served to test the influence of T-type Ca channels in spinal
      nerve-injured rats. OBJECTIVE: To determine the changes of T-type Ca channels in
      dorsal root ganglion (DRG) neurons of different sizes and the contribution to
      neuronal firing and painful behavior in neuropathic pain induced by nerve injury.
      SUMMARY OF BACKGROUND DATA: T-type and high-voltage-activated Ca channels play an
      important role in the transmission of nociceptive signals, especially in neuronal
      hyperexcitability in neuropathic pain. However, little is known about how nerve
      injury affects T-type Ca channels in DRG neurons of different sizes. METHODS: The
      effect of intrathecal administration of mibefradil in nerve-ligated rats was
      examined by painful behavior testing and current clamp. The changes of T-type Ca
      channels in DRG neurons caused by spinal nerve ligation were determined by RT-PCR
      analysis and voltage clamp. RESULTS: Spinal nerve injury significantly increased
      current density of T-type Ca channels in small DRG neurons. In addition, nerve
      injury significantly increased the percentage of T-type Ca channels in medium and
      large DRG neurons. Nerve injury significantly increased the mRNA levels of Cav3.2
      and Cav3.3 in DRGs. Block of T-type Ca channels on mibefradil administration
      significantly normalized painful behavior and hyperexcitability in neuronal
      firing in spinal nerve-injured rats. CONCLUSION: Our study first indicated the
      upregulation of functional T-type Ca channels in DRG neurons of different sizes
      and the changes in different subtypes of T-type Ca channels by spinal nerve
      injury. Considering the effect of blocking T-type Ca channels in painful behavior
      and abnormal neuronal firing in rats with nerve injury, our results suggest that
      T-type Ca channels are potential therapeutic targets for the treatment of spinal
      nerve ligation-induced neuropathic pain.

PMID- 22972513
TI  - A misdiagnosed iliac pseudoaneurysm complicated lumbar disc surgery performed 13
      years ago.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a unique case of iliac
      pseudoaneurysm-complicated lumbar disc surgery performed 13 years ago. SUMMARY OF
      BACKGROUND DATA: Major vascular injury is an unusual but life-threatening
      complication of lumbar disc surgery. If a major vascular injury is unnoticed, the
      late complications, pseudoaneurysm, may be diagnosed years after primary lumbar
      disc surgery. Pseudoaneurysm can lead to compression of adjacent neurovascular
      structures; however, erosion into the adjacent vertebras and presentation with
      symptoms of nerve root irritation are rare. METHODS: The patient was a 54-year
      old man who presented with pain and numbness in right hip and leg. Examination
      was normal. A plain radiograph showed destruction of the fourth and fifth lumbar
      vertebras. Magnetic resonance image showed a retroperitoneal mass eroding into
      the adjacent vertebras. The mass was primarily misdiagnosed as a neoplasm and a
      percutaneous needle biopsy was recommended. Before puncture, the computed
      tomographic angiogram confirmed it to be a pseudoaneurysm of left common iliac
      artery. Then, implantation of a covered stent was undergone. RESULTS: After
      implantation of a covered stent, the symptoms were relieved immediately. At the
      12-month follow-up, the patient remained asymptomatic, and a computed tomographic
      angiogram revealed progressive shrinkage of the mass and significant healing of
      the eroded vertebras. CONCLUSION: As an unusual complication of lumbar disc
      surgery, iliac pseudoaneurysm can present with radiating pain even after 13 years
      and erode into the adjacent vertebras producing appearances mimicking a tumor.
      For mass located anterior to vertebras, the percutaneous biopsy must be
      cautiously performed, and a contrast-enhanced computed tomographic scan is
      necessary.

PMID- 22972514
TI  - Spine is the most cited orthopedic journal.

PMID- 22972515
TI  - Oats (Avena strigosa) as winter forage for dairy cows in Vietnam: an on-farm
      study.
AB  - In North Vietnam, during winter, alternative forage resources are needed to
      balance the feed ration of dairy cows. The objective of this study was to
      investigate the effect of oat forage as a component of traditional winter
      roughage diets on feed intake, milk production and feeding cost in dairy cows.
      The study was conducted on-farm using 24 mid-lactation Holstein-Friesian cows.
      The feeding experiment consisted of two successive periods and two dietary
      treatments per period. Traditional basal diets included fresh tropical grasses,
      maize silage and hay. The oat forage had no effect on the dry matter intake of
      the basal diet, but the total crude protein intake was higher in cows fed with
      oat diets than in those fed with control diets. The yield of butterfat-corrected
      milk (FCM) was not significantly different between diets during period 1, but
      there was a trend (P = 0.078) of higher FCM yields in cows fed with the oat diet
      compared to those with control diet during period 2 (17.3 vs. 16.3 kg/day). The
      decline rate in milk yield was significantly higher (P < 0.001) in cows fed with
      control diets than in those fed with oat diets in both experimental periods. The
      total feeding cost of cows fed with oat diets was on average 12 % lower than
      those fed with control diets (P < 0.01). So, the oat forage is an important
      winter resource for cows in North Vietnam allowing higher milk yield whilst
      reducing feeding cost, compared to traditional roughage diets.

PMID- 22972516
TI  - Dispersion durations of P-wave and QT interval in children with congenital heart
      disease and pulmonary arterial hypertension.
AB  - This study aimed to investigate homogeneity disorders of ventricular
      repolarization and atrial conduction via QT dispersion and P-wave dispersion in
      children with congenital heart disease (CHD) and pulmonary arterial hypertension
      (PAH). Three groups of 20 each were generated and involved in this study. The
      first group included 20 children with both CHD and PAH. The second group
      consisted of 20 children with CHD but no PAH, and the third group was composed of
      20 age- and sex-matched healthy children. Electrocardiographic records were used
      to determine P-wave, QT, and corrected QT (QTc) dispersions. The pulmonary
      hypertension group compared with the group having no pulmonary hypertension and
      the control group showed a significantly longer P-wave dispersion duration (39.10
      +/- 9.54 vs. 26.30 +/- 4.99 ms, p < 0.001; and 24.80 +/- 6.94 ms, p < 0.001,
      respectively) and QT dispersion duration (52.80 +/- 15.11 vs. 37.60 +/- 6.00 ms,
      p < 0.001; and 35.00 +/- 7.77 ms, p < 0.001, respectively). In addition, the
      durations of maximum QTc and QTc dispersion were significantly longer in
      pulmonary hypertension group than in the other two groups. The risk of atrial and
      ventricular arrhythmia was found to be increased in the patients with both CHD
      and PAH. Physicians should pay close attention to possible atrial and ventricular
      arrhythmias during the treatment and follow-up evaluation of these patients.

PMID- 22972517
TI  - Improving teamwork, confidence, and collaboration among members of a pediatric
      cardiovascular intensive care unit multidisciplinary team using simulation-based
      team training.
AB  - Findings show that simulation-based team training (SBTT) is effective at
      increasing teamwork skills. Postpediatric cardiac surgery cardiac arrest (PPCS
      CA) is a high-risk clinical situation with high morbidity and mortality. Whereas
      adult guidelines managing cardiac arrest after cardiac surgery are available,
      little exists for pediatric cardiac surgery. The authors developed a post-PPCS-CA
      algorithm and used SBTT to improve identification and management of PPCS-CA in
      the pediatric cardiovascular intensive care unit. Their goal was to determine
      whether participation aids in improving teamwork, confidence, and communication
      during these events. The authors developed a simulation-based training course
      using common postcardiac surgical emergency scenarios with specific learning
      objectives. Simulated scenarios are followed by structured debriefings.
      Participants were evaluated based on critical performance criteria, key elements
      in the PPCS-CA algorithm, and Team Strategies and Tools to Enhance Performance
      and Patient Safety (Team STEPPS) principles. Surveys performed before,
      immediately after, and 3 months after participation evaluated perception of
      skill, knowledge, and confidence. The study had 37 participants (23 nurses, 5
      cardiology/critical care trainees, 5 respiratory therapists, and 4 noncategorized
      subjects). Confidence and skill in the roles of team leader, advanced airway
      management, and cardioversion/defibrillation were increased significantly (p <
      0.05) immediately after training and 3 months later. A significant increase (p <
      0.05) also was observed in the use of Team STEPPS concepts immediately after
      training and 3 months later. This study showed SBTT to be effective in improving
      communication and increasing confidence among members of a multidisciplinary team
      during crisis scenarios. Thus, SBTT provides an excellent tool for teaching and
      implementing new processes.

PMID- 22972519
TI  - Surface functionality of nanoparticles determines cellular uptake mechanisms in
      mammalian cells.
AB  - Nanoparticles (NPs) are versatile scaffolds for numerous biomedical applications
      including drug delivery and bioimaging. The surface functionality of NPs
      essentially dictates intracellular NP uptake and controls their therapeutic
      action. Using several pharmacological inhibitors, it is demonstrated that the
      cellular uptake mechanisms of cationic gold NPs in both cancer (HeLa) and normal
      cells (MCF10A) strongly depend on the NP surface monolayer, and mostly involve
      caveolae and dynamin-dependent pathways as well as specific cell surface
      receptors (scavenger receptors). Moreover, these NPs show different uptake
      mechanisms in cancer and normal cells, providing an opportunity to develop NPs
      with improved selectivity for delivery applications.

PMID- 22972520
TI  - Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed
      atherogenic plus high-fat diet.
AB  - BACKGROUND: The transcription factor nuclear factor-E2-related factor-2 (Nrf2)
      inhibits lipid accumulation and oxidative stress in the liver by interfering with
      lipogenic pathways and inducing antioxidative stress genes. METHODS: The
      involvement of Nrf2 in defense against the development of steatohepatitis was
      studied in an experimental model induced by an atherogenic plus high-fat (Ath +
      HF) diet. Wild-type (WT) and Nrf2-null mice were fed the diet. Their specimens
      were analyzed for pathology as well as for the expression levels of genes
      involved in fatty acid metabolism and those involved via the Nrf2 transcriptional
      pathway. RESULTS: In Nrf2-null mice fed the diet, steatohepatitis developed
      rapidly, leading to precirrhosis. The Ath + HF diet increased hepatic
      triglyceride levels and changed fatty acid composition in both mouse groups.
      However, oleic acid (C18:1 n-9) predominated in the livers of Nrf2-null mice.
      Correlating well with the pathology, the mRNA levels of the factors involved in
      fatty acid metabolism (Lxr, Srebp-1a, 1c, Acc-1, Fas, Scd-1, and Fatty acid
      transporting peptides 1, 3, 4), the inflammatory cytokine genes (Tnf-alpha and IL
      1beta), and the fibrogenesis-related genes (Tgf-beta1 and alpha-Sma) were
      significantly increased in the livers of Nrf2-null mice fed the diet, compared
      with the levels of these factors in matched WT mice. Oxidative stress was
      significantly increased in the livers of Nrf2-null mice fed the diet. This change
      was closely associated with the decreased levels of antioxidative stress genes.
      CONCLUSIONS: Nrf2 deletion leads to the rapid onset and progression of
      steatohepatitis induced by an Ath + HF diet, through both up-regulation of co
      regulators of fatty acid metabolism and down-regulation of oxidative metabolism
      regulators in the liver.

PMID- 22972522
TI  - Wentilactone B from Aspergillus wentii induces apoptosis and inhibits
      proliferation and migration of human hepatoma SMMC-7721 cells.
AB  - Wentilactone B (EN-48-57) is one of the six derivatives separated from
      Aspergillus wentii (EN-48). Of these derivatives, Wentilactone B exerted a more
      significant antibacterial and cytotoxic activity in several tumor cell lines. The
      present study demonstrates that Wentilactone B could efficiently induce SMMC-7721
      cells apoptosis, but not normal hepatic cells, as measured by an inverted
      microscope, 4',6-diamidino-2-phenylindole staining and flow cytometry. In
      addition, Wentilactone B could inhibit the metastasis of SMMC-7721 cells, which
      was detected by colony formation, scratch migration and a transwell assay, and
      could induce a series of intracellular events, including the down-regulation of
      CD44 and epidermal growth factor receptor proteins. In conclusion, Wentilactone B
      inhibited the growth of SMMC-7721 cells by triggering apoptosis and inhibiting
      metastasis.

PMID- 22972521
TI  - Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue
      and involved in cell metastasis.
AB  - Protein inhibitor of activated STAT-1 (PIAS1) is a novel modulator of the
      JAK/STAT signaling pathway that negatively regulates the inflammatory response.
      It has been also reported to be downregulated in a variety of human cancer cell
      lines. However, the role of PIAS1 in gastric cancer remains unclear. In this
      study, we investigated the prognostic value of PIAS1 expression and its regulated
      mechanisms in gastric cancer cell metastasis. Therefore, the expression of PIASI
      was explored in gastric cancer tissues and adjacent tissues of gastric cancer
      with 31 cases of patients, and the prognostic value was analyzed. In addition,
      the growth and invasion in SGC7901 cells were investigated in the restoration of
      PIAS1 expression with Ad5/F35-PIAS1 or Ad5/F35-vector or PBS treatment, and the
      activity of P38MAPK, P-P38MAPK, JNK/SAPK, P-JNK/SAPK, ERK and P-ERK, were
      detected by western blotting. The tumor migratory factors MMP-9, MMP-2 and ICAM-1
      were analyzed by western blotting. The results demonstrated that 22 of 31 (70.9%)
      gastric cancer specimens showed low levels of PIAS1 expression from
      immunohistochemistry staining using tissue microarrays. Statistical analysis
      suggested that the downregulation of PIAS1 was significantly correlated with
      tumor staging. Furthermore, we found that the restoration of PIAS1 expression
      mediated by Ad5/F35 virus suppressed cell proliferation and invasion accompanied
      by the inhibition of P38MAPK and ERK protein expression and activity, but not
      JNK/SAPK protein. Notably, PIAS1 restoration with the transfection of Ad5/F35
      PIAS1 robustly decreased the expression of tumor migratory factors including MMP
      9, MMP-2 and ICAM-1 compared to Ad5/F35-vector. These data suggest that PIAS1 may
      function as a tumor suppressor to regulate gastric cancer cell metastasis by
      targeting the MAPK signaling pathway.

PMID- 22972523
TI  - Preparation, characterization and related in vivo release, safety and toxicity
      studies of long acting lanreotide microspheres.
AB  - The goal of this project was to prepare long-acting lanreotide acetate
      poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and
      in vitro release, safety and toxicology of these preparations. Long-acting
      lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period
      were prepared by a multiple-emulsion solvent evaporation method. Physical
      characterization, as well as the analysis of the in vivo and in vitro release,
      safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were
      conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The
      lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent
      evaporation had smooth surfaces, uniform particle size and stable lanreotide
      loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA
      microspheres could continuously release lanreotide for 5 weeks. The safety of
      these long acting lanreotide microspheres was good in the following animal
      models: active systemic anaphylaxis test in guinea pigs, passive cutaneous
      anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test
      after subcutaneous administration in rabbits and muscle stimulation test in
      rabbits. Furthermore, no significant acute toxicity or chronic toxicity was
      observed after administration of lanreotide acetate PLGA microspheres in beagle
      dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that
      were prepared in this study exhibited beneficial characteristics in apparent
      property and structural stability, as well as in release trends in vivo and in
      vitro.

PMID- 22972524
TI  - Long-term durability of the response to desmopressin in female and male nocturia
      patients.
AB  - AIMS: To explore the durability of efficacy and gender differences during chronic
      administration of desmopressin in nocturia. METHODS: This pooled analysis of
      three short-term efficacy studies, with extensions, of desmopressin administered
      as orally disintegrating tablet (ODT) or solid tablet in nocturia treatment,
      comprised 351 patients completing 40-56 weeks' treatment. Efficacy endpoints of
      change in number of nocturnal voids and duration of initial undisturbed sleep
      period from baseline were analyzed to determine response durability and gender
      differences. RESULTS: The mean decrease in number of nocturnal voids during short
      term treatment was maintained and further reduced during the long term. At 52
      weeks, the mean decrease in number of nocturnal voids from baseline reached 1.4
      2.1 voids for desmopressin ODT 25-100 ug. Following 40-week tablet treatment, the
      decrease in number of nocturnal voids was 0.8-1.5 for desmopressin 100-400 ug.
      The mean decrease in nocturnal voids (25-50 ug ODT) was greater for females than
      males. For females, the improvement in initial period of undisturbed sleep was
      2.5-3 hr for desmopressin ODT 25-100 ug, compared with 1.3-2.6 hr for males. No
      gender difference in efficacy was seen in the tablet studies. CONCLUSIONS: The
      decrease in nocturnal voids and improvement in sleep with short-term desmopressin
      treatment were maintained throughout long-term treatment. A durable gender
      difference in efficacy in favor of females was observed with desmopressin ODT 25
      ug. Further, large-scale long-term trials are needed to confirm the durability of
      efficacy with gender-specific doses of desmopressin.

PMID- 22972525
TI  - Systematic review and meta-analysis of outcomes following emergency surgery for
      Clostridium difficile colitis.
AB  - BACKGROUND: Only a small proportion of patients with severe Clostridium difficile
      infection (CDI) undergo emergency surgery, the timing and nature of which is
      unclear. The aim of this study was to describe the operations performed and to
      identify factors predictive of death following emergency surgery for CDI.
      METHODS: A systematic review of published literature was performed for studies
      comparing survivors and non-survivors of emergency surgery for CDI. Meta-analysis
      was carried out for 30-day and in-hospital mortality. RESULTS: Overall 31 studies
      were included, which presented data on a total of 1433 patients undergoing
      emergency surgery for CDI. Some 1.1 per cent of all patients with CDI and 29.9
      per cent with severe CDI underwent emergency surgery, although rates varied
      between studies (0.2-7.6 and 2.2-86 per cent respectively). The most commonly
      performed operation was total colectomy with end ileostomy (89.0 per cent, 1247
      of 1401 detailed surgical procedures). When total colectomy with end ileostomy
      was not performed, reoperation to resect further bowel was needed in 15.9 per
      cent (20 of 126). Where described, the 30-day mortality rate was 41.3 per cent
      (160 of 387). Meta-analysis of high-quality studies revealed that the strongest
      predictors of postoperative death were those relating to preoperative
      physiological status: preoperative intubation, acute renal failure, multiple
      organ failure and shock requiring vasopressors. CONCLUSION: This systematic
      review supports total colectomy with end ileostomy as the primary surgical
      treatment for patients with severe CDI; other surgical procedures are associated
      with high rates of reoperation and mortality. Less extensive surgery may have a
      role in selected patients with earlier-stage disease.

PMID- 22972526
TI  - Proteome analysis of altered proteins in streptozotocin-induced diabetic rat
      kidney using the fluorogenic derivatization-liquid chromatography-tandem mass
      spectrometry method.
AB  - To find new molecular markers for early diagnosis of diabetic nephropathy, we
      applied fluorogenic derivatization-liquid chromatography-tandem mass spectrometry
      to identify the differentially expressed proteins in the kidney of control and
      streptozotocin-induced diabetic rats. The Sprague-Dawley rats were injected with
      the sodium citrate buffer or streptozotocin and then killed after 1, 4, 12 and 24
      weeks. The results showed that seven proteins were significantly changed after 1
      week of injection. Only one protein had significantly changed after 4 weeks of
      injection. However, after 12 weeks of injection, the number of altered proteins
      rose to 10. After 24 weeks of injection, 18 proteins had altered significantly.
      Five common proteins were significantly altered at week 12 and 24 after
      injection, respectively. Importantly, these proteins appeared prior to
      microalbuminuria and may serve as new biomarkers that are able to improve early
      detection of and new drug development for diabetic-related nephropathy.

PMID- 22972527
TI  - Using rituximab plus fludarabine and cyclophosphamide as a treatment for
      refractory mixed cryoglobulinemia associated with lymphoma.
AB  - OBJECTIVE: Treatment of refractory mixed cryoglobulinemia (MC) with severe organ
      involvement remains challenging. Fludarabine, cyclophosphamide, and rituximab
      (FCR) treatment is highly effective for patients with chronic lymphocytic
      leukemia and marginal-zone lymphoma. We first report the safety and efficacy of
      FCR treatment in severe and refractory MC vasculitis associated with lymphoma.
      METHODS: We report the safety and efficacy of fludarabine (40 mg/m(2) orally on
      days 2-4), cyclophosphamide (250 mg/m(2) orally on days 2-4), and rituximab (375
      mg/m(2) on day 1), every 4 weeks, for 3 to 6 cycles in 7 consecutive patients
      with severe and refractory MC. RESULTS: Clinical features of MC included purpura
      (n = 7), polyneuropathy (n = 6), and kidney (n = 4) and cardiac involvement (n =
      2). Previous treatment included rituximab (n = 5), corticosteroids (n = 5),
      antiviral therapy (n = 5), cyclophosphamide (n = 3), and plasmapheresis (n = 2).
      All patients achieved clinical response, with 3 patients (42.9%) achieving a
      complete remission and 4 patients (57.1%) a partial remission. Cryoglobulin
      decreased from 0.94 to 0.41 gm/liter (P = 0.015). After a followup of 27 months,
      2 patients experienced a relapse of MC. Five patients (71.4%) experienced side
      effects, including cytopenia (n = 5), pneumopathy (n = 2), and serum sickness (n
      = 1). CONCLUSION: The FCR regimen represents an effective treatment in severe and
      refractory MC.

PMID- 22972528
TI  - Complications in orthopaedic surgery.

PMID- 22972529
TI  - A synergistically enhanced T(1) -T(2) dual-modal contrast agent.
AB  - Monodisperse Gd(2) O(3) -embedded iron oxide (GdIO) nanoparticles can
      simultaneously enhance the local magnetic field intensities of each other under
      an external magnetic field and result in synergistic enhancement of T(1)  and
      T(2)  effects. GdIO nanoparticles have the unique property to be both T(1)  and
      T(2)  contrast agents and can potentially lead to higher accuracy in cancer
      diagnosis, particularly liver tumors.

PMID- 22972530
TI  - Non-communicable disease: a welcome and long needed addition to the WHO's 2012
      World Heath Statistics.
AB  - The World Health Organization's annual report World Health Statistics 2012 was
      recently published. In addition to annually published indicators of health, this
      year's report contains a highlighted new section on non-communicable diseases and
      their impact on world health. The section gives particular attention to
      hypertension and obesity. Interestingly, despite worldwide increases in obesity
      and metabolic syndrome, hypertension rates have actually improved in wealthy
      nations since 1980, while rates have greatly increased in developing regions and
      particularly in Africa. Potential contributors to these disparities likely
      include access to screening and treatment, and the rise of high sodium and low
      potassium processed foods in poorer nations. It will be imperative in years to
      come to identify and employ the success seen in wealthy nations worldwide to
      improve outcomes and productivity in the developing world.

PMID- 22972531
TI  - Mitochondria, myocardial remodeling, and cardiovascular disease.
AB  - The process of muscle remodeling lies at the core of most cardiovascular
      diseases. Cardiac adaptation to pressure or volume overload is associated with a
      complex molecular change in cardiomyocytes which leads to anatomic remodeling of
      the heart muscle. Although adaptive at its beginnings, the sustained cardiac
      hypertrophic remodeling almost unavoidably ends in progressive muscle
      dysfunction, heart failure and ultimately death. One of the features of cardiac
      remodeling is a progressive impairment in mitochondrial function. The heart has
      the highest oxygen uptake in the human body and accordingly it has a large number
      of mitochondria, which form a complex network under constant remodeling in order
      to sustain the high metabolic rate of cardiac cells and serve as Ca(2+) buffers
      acting together with the endoplasmic reticulum (ER). However, this high
      dependence on mitochondrial metabolism has its costs: when oxygen supply is
      threatened, high leak of electrons from the electron transport chain leads to
      oxidative stress and mitochondrial failure. These three aspects of mitochondrial
      function (Reactive oxygen species signaling, Ca(2+) handling and mitochondrial
      dynamics) are critical for normal muscle homeostasis. In this article, we will
      review the latest evidence linking mitochondrial morphology and function with the
      process of myocardial remodeling and cardiovascular disease.

PMID- 22972534
TI  - False-positive amphetamine/ecstasy (MDMA/3,4-methylenedioxymethamphetamine)
      (CEDIA) and ecstasy (MDMA/3,4-methylenedioxymethamphetamine) (DRI) test results
      with fenofibrate.
AB  - This case report describes a false-positive amphetamine/ecstasy [3,4
      methylenedioxymethamphetamine (MDMA)] and ecstasy (MDMA) screen after therapeutic
      use of antihyperlipidemic drug, fenofibrate. A 60-year-old male patient was
      admitted to inpatient psychiatry unit with the diagnosis of alcohol dependency.
      He was prescribed diazepam 30 mg/day, thiamine 300 mg/day, and naltrexone 50
      mg/day. He had also been using fenofibrate 267 mg/day for 3 years for
      hyperlipidemia and trazodone 100 mg/day for 5 months for insomnia. On routine,
      urine drugs-of-abuse screening amphetamine/MDMA (CEDIA) test was positive for 4
      different occasions and MDMA (DRI) test was positive on 5 different occasions.
      Gas chromatography/mass spectrometry confirmation of the first positive 3 samples
      were negative for amphetamine and MDMA. After discontinuation of fenofibrate,
      amphetamine/MDMA, and MDMA immunoassay results turned out to be negative. Caution
      should be given to interpretation of amphetamine/MDMA (CEDIA) and MDMA (DRI)
      tests in patients taking fenofibrate. Specific confirmation with a suitable
      method should be used to prevent erroneous interpretations.

PMID- 22972532
TI  - Heart rate and blood pressure: any possible implications for management of
      hypertension?
AB  - Hypertension is a common clinical problem and a major risk factor for
      cardiovascular disease and stroke. Elevated heart rate is associated with
      elevated blood pressure, increased risk for hypertension, and, among
      hypertensives, increased risk for cardiovascular disease. Despite these important
      relationships, heart rate is generally not a major consideration in choosing
      antihypertensive medications. In part, this is due to a lack of evidence
      supporting heart rate lowering as a therapeutic strategy in hypertension.
      Additionally, while there is a positive correlation between heart rate and
      peripheral blood pressure, there is an inverse relationship between heart rate
      and central blood pressure. The use of antihypertensive medications, specifically
      medications that affect heart rate, may not reliably reduce central blood
      pressure to a similar extent as observed peripherally. We review the relationship
      between heart rate and peripheral and central blood pressure, with a focus on the
      implications for chronotropic therapy in hypertension.

PMID- 22972535
TI  - Valproic Acid significantly lowers serum concentrations of olanzapine-an
      interaction effect comparable with smoking.
AB  - BACKGROUND: Preliminary reports have indicated that valproic acid (VPA) reduces
      serum concentrations of olanzapine (OLZ). The aim of this study was to
      investigate the impact of VPA and other antiepileptic drugs (AEDs) on serum
      concentrations of OLZ and 3 of its major metabolites in a large-scale material of
      therapeutic drug monitoring samples. METHODS: OLZ-treated patients were
      stratified into subgroups according to coadministration of various AEDs, that is,
      lamotrigine (LTG; 110 patients/153 samples), VPA (92/166), LTG + VPA (7/12),
      carbamazepine (CBZ) (8/8), oxcarbazepine (2/3), gabapentin (3/4), levetiracetam
      (2/3), and topiramate (2/2). A control group treated with OLZ without AEDs was
      also included (205/247). Dose-adjusted serum concentrations (C:D ratios) of OLZ
      and its major metabolites (N-desmethyl, N-oxide, and 10-N-glucuronide) were
      compared between AED subgroups and controls, using linear mixed model analyses
      with age, gender, and cigarette smoking as covariates. RESULTS: Significantly
      lower OLZ C:D ratios were found in patients comedicated with VPA (-32%, P <
      0.001), VPA + LTG (-31%, P < 0.01), and CBZ (-50%, P < 0.001), compared with
      controls. The 10-N-glucuronide concentration was significantly lower in patients
      comedicated with VPA (-26%, P < 0.001), whereas CBZ significantly lowered N
      desmethyl (-42%, P = 0.001) and N-oxide (-52%, P < 0.001) metabolite
      concentrations. C:D ratios of OLZ and metabolites were not significantly affected
      by comedication with LTG or any of the other AEDs. All covariates were
      significant determinants of OLZ C:D ratio, that is, age 60 years or above +35% (P
      < 0.001), female gender +11% (P < 0.01) and smoking -32% (P < 0.001).
      CONCLUSIONS: Concurrent use of VPA significantly decreases serum concentrations
      of OLZ to an extent comparable with smoking. The mechanism behind the interaction
      could not be derived from the results of this study.

PMID- 22972536
TI  - Association between lamotrigine concentrations and ABCB1 polymorphisms in
      patients with epilepsy.
AB  - BACKGROUND: Epilepsy is treated with a variety of anticonvulsants that are often
      used concomitantly. Therefore, therapeutic drug monitoring is often necessary.
      Along with clinical and environmental factors, genetic predisposition has been
      recognized to be relevant for interindividual variability in drug response.
      Polymorphic transporter proteins such as P-glycoprotein significantly influence
      pharmacokinetics and bioavailability of many structurally unrelated drugs. The
      aim of the study was to evaluate the impact of polymorphisms in the P
      glycoprotein-encoding gene ABCB1 (C1236T, G2677T/A, C3435T) on antiepileptic drug
      disposition. METHODS: We recruited 222 patients with epilepsy who were prescribed
      lamotrigine in monotherapy or polytherapy. Lamotrigine plasma concentrations were
      analyzed and compared with ABCB1 gene variants. The ABCB1 genotyping was
      performed by real-time polymerase chain reaction methods. The therapeutic drug
      monitoring was performed by high-performance liquid chromatography-diode array
      detector (DAD) and immunoassay. RESULTS: A significant correlation was confirmed
      between lamotrigine concentration and additional drugs (P < 0.001). In the whole
      group, statistical analysis showed correlations between lamotrigine
      concentrations and ABCB1 C1236T variants: 10.1 and 6.5 MUmol/L for CC versus CT +
      TT, respectively (P = 0.021), and for dose corrected lamotrigine 0.068 and 0.053
      MUmol.L.mg, for CC versus CT + TT, respectively (P = 0.017). Analysis of a
      specific haplotype showed that 1236C-2677G-3435C carriers had higher lamotrigine
      concentrations than 1236T-2677G-3435T carriers (P < 0.001), followed by 1236T
      2677T-3435C carriers (P < 0.001). CONCLUSIONS: ABCB1 C1236T, G2677T/A, C3435T
      polymorphisms have an influence on lamotrigine serum concentrations.

PMID- 22972537
TI  - How can analytical diagnostics in clinical toxicology be successfully performed
      today?
AB  - This article discusses current strategies for efficient analytical diagnostics in
      clinical toxicology. The tasks for such diagnostics, different analytical
      strategies and various methods were reviewed. They cover mainly gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry
      procedures for target or comprehensive screening for drugs (of abuse) and
      poisons, and for quantification in blood. Quality control aspects and strategies
      for competent interpretation of the analytical result in correlation with the
      clinical signs presented by the patient are discussed.

PMID- 22972538
TI  - Determinants of adherence to delayed-release doxylamine and pyridoxine in
      patients with nausea and vomiting of pregnancy.
AB  - OBJECTIVE: Women often hesitate to take medications in pregnancy due to fears of
      perceived potential fetal damage. The authors' objective is to identify the
      determinants of adherence to delayed-release doxylamine-pyridoxine (Diclectin) in
      patients with nausea and vomiting of pregnancy (NVP). METHODS: The authors
      performed a prespecified secondary analysis of a multicenter double-blind
      randomized controlled trial of Diclectin versus placebo for the treatment of NVP.
      Data on adherence to study medication were collected in all patients. The primary
      outcome of this analysis was adherence to study medication, which was determined
      by pill counting and patient diaries. The treatment regimen in the original trial
      was not fixed and depended on patient's symptoms. There was no difference in the
      adherence rates between subjects in the Diclectin or placebo arms of the study,
      so the 2 arms were analyzed as one cohort. The degree of adherence was analyzed
      in the various subgroups. Subsequently, a multiple linear regression model was
      constructed to identify predictors to adherence. RESULTS: Two hundred fifty-eight
      women were included in this analysis. There were no differences in adherence
      rates according to ethnicity, race, or the presence of adverse events. Gravidity,
      average number of prescribed tablets per day, site of enrollment, and change in
      NVP severity measured by the pregnancy unique-quantification of emesis score were
      associated with adherence. In multivariable analysis, average number of tablets
      per day, change in pregnancy unique-quantification of emesis, number of treatment
      days, site of enrollment were significantly predictive of adherence, with the
      former being negatively correlated. CONCLUSION: Adherence to antinauseants for
      NVP is affected by number of tablets prescribed per day, and treatment duration
      and effectiveness.

PMID- 22972539
TI  - Predictive performance of a busulfan pharmacokinetic model in children and young
      adults.
AB  - BACKGROUND: Recently a pediatric pharmacokinetic (PK) model was developed for
      busulfan to explain the wide variability in PK of busulfan in children, as this
      variability is known to influence the outcome of hematopoietic stem cell
      transplantation in terms of toxicity and event free survival. This study assesses
      the predictive performance of this busulfan PK model in a new, more diverse
      pediatric population, including data from patients with different underlying
      diseases, ethnicities, body weights, ages, and body mass indices, from 5
      international pediatric transplant centers. PATIENTS AND METHODS: The previously
      published (original) busulfan PK model was developed from data of 245 patients
      (0.1-26 years of age). To externally validate this model, data were collected
      from another 158 patients (0.1-35 years) who underwent hematopoietic stem cell
      transplantation in 5 international transplant centers. Observed versus predicted
      plots, normalized prediction distribution error analysis, refit of the model on
      the external (n = 158) and combined datasets (n = 403), and subpopulation
      analyses were evaluated. RESULTS: The original busulfan PK model was found to be
      stable and parameter estimates precise. Concentrations predicted by this model
      were in good agreement with the observed concentrations from the 5 external
      datasets. Plasma concentrations in patients with different underlying diseases,
      ethnicities, body weights, ages, and body mass indices were adequately predicted.
      CONCLUSIONS: Our pediatric busulfan PK model has been externally validated. This
      model predicts busulfan concentrations in pediatric and young adult patients
      ranging between 3 and 86 kg without bias and with good precision, regardless of
      transplant center, underlying disease, ethnicity, body weight age, or body mass
      index. This busulfan PK model forms the basis for individualized busulfan dosing.

PMID- 22972540
TI  - Establishment of thiopurine S-methyltransferase gene knockdown in jurkat T
      lymphocytes: an in vitro model of TPMT polymorphism.
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an excellent example of an
      enzyme whose pharmacogenetic polymorphisms affect efficacy and toxicity of a
      drug. The association between TPMT activity and thiopurine-related
      myelosuppression is well recognized. To study the significance of TPMT deficiency
      in thiopurine metabolism and immunosuppressive activity in vitro, we established
      RNA interference-based TPMT knockdown (kd) in a Jurkat cell line. RESULTS: In
      Jurkat TPMT kd cells, TPMT expression was reduced to 73% at the RNA level and 83%
      at the protein level. TPMT kd cells were more sensitive to 6-mercaptopurine (6
      MP) (10 MUmol/L) and 6-thioguanine (6-TG) (8 MUmol/L) than wild-type (wt) cells,
      (32% versus 20%) and (18% versus 9%), respectively. Both Jurkat wt and kd cells
      were more sensitive to 6-TG-induced apoptosis than to 6-MP. 6-TG activity was
      also more affected by TPMT levels than was 6-MP as reflected by IC60,
      concentrations that is, 6-MP [4.6 MUmol/L (wt) and 4.7 MUmol/L (kd)], 6-TG [2.7
      MUmol/L (wt) and 0.8 MUmol/L (kd)]. IC60 concentrations induced significant
      apoptosis in both Jurkat wt and kd cells (257%, versus 314%) with 6-MP and (323%
      versus 306%) with 6-TG, respectively. At IC60 (6-MP) 6-thioguanine nucleotides (6
      TGN) accumulation in cells was 518 versus 447 pmol/million cells in wt and kd
      cells, respectively. On the other hand 6-TGN accumulation at IC60 (6-TG) was 477
      versus 570 pmol/million cells in wt and kd cells, respectively. 6-Methylated
      mercaptopurine (6-MeMP) concentrations were more affected than 6-TGN by TPMT kd
      (194 versus 10 pmol/million cells) in wt and kd cells, respectively. CONCLUSION:
      We conclude that TPMT kd cells are an appropriate in vitro model to investigate
      the significance of TPMT deficiency with thiopurine therapy and could be helpful
      in understanding possible clinical consequences of TPMT polymorphism.

PMID- 22972541
TI  - Reflections about off-label use of anticancer drugs.

PMID- 22972542
TI  - Prophylactic drug monitoring of itraconazole in an oncohematological pediatric
      patient population.

PMID- 22972544
TI  - A gene-free formulation of classical quantitative genetics used to examine
      results and interpretations under three standard assumptions.
AB  - Quantitative genetics (QG) analyses variation in traits of humans, other animals,
      or plants in ways that take account of the genealogical relatedness of the
      individuals whose traits are observed. "Classical" QG, where the analysis of
      variation does not involve data on measurable genetic or environmental entities
      or factors, is reformulated in this article using models that are free of
      hypothetical, idealized versions of such factors, while still allowing for
      defined degrees of relatedness among kinds of individuals or "varieties." The
      gene-free formulation encompasses situations encountered in human QG as well as
      in agricultural QG. This formulation is used to describe three standard
      assumptions involved in classical QG and provide plausible alternatives. Several
      concerns about the partitioning of trait variation into components and its
      interpretation, most of which have a long history of debate, are discussed in
      light of the gene-free formulation and alternative assumptions. That discussion
      is at a theoretical level, not dependent on empirical data in any particular
      situation. Additional lines of work to put the gene-free formulation and
      alternative assumptions into practice and to assess their empirical consequences
      are noted, but lie beyond the scope of this article. The three standard QG
      assumptions examined are: (1) partitioning of trait variation into components
      requires models of hypothetical, idealized genes with simple Mendelian
      inheritance and direct contributions to the trait; (2) all other things being
      equal, similarity in traits for relatives is proportional to the fraction shared
      by the relatives of all the genes that vary in the population (e.g., fraternal or
      dizygotic twins share half of the variable genes that identical or monozygotic
      twins share); (3) in analyses of human data, genotype-environment interaction
      variance (in the classical QG sense) can be discounted. The concerns about the
      partitioning of trait variation discussed include: the distinction between traits
      and underlying measurable factors; the possible heterogeneity in factors
      underlying the development of a trait; the kinds of data needed to estimate key
      empirical parameters; and interpretations based on contributions of hypothetical
      genes; as well as, in human studies, the labeling of residual variance as a non
      shared environmental effect; and the importance of estimating interaction
      variance.

PMID- 22972543
TI  - Oral complications of cancer and cancer therapy: from cancer treatment to
      survivorship.
AB  - Answer questions and earn CME/CNE Oral complications resulting from cancer and
      cancer therapies cause acute and late toxicities that may be underreported,
      underrecognized, and undertreated. Recent advances in cancer treatment have led
      to changes in the incidence, nature, and severity of oral complications. As the
      number of survivors increases, it is becoming increasingly recognized that the
      aggressive management of oral toxicities is needed to ensure optimal long-term
      oral health and general well-being. Advances in care have had an impact on
      previously recognized oral complications and are leading to newly recognized
      adverse effects. Here, the authors briefly review advances in cancer therapy,
      including recent advances in surgery, oral care, radiation therapy, hematopoietic
      cell transplantation, and medical oncology; describe how these advances affect
      oral health; and discuss the frequent and/or severe oral health complications
      associated with cancer and cancer treatment and their effect upon long-term
      health. Although some of the acute oral toxicities of cancer therapies may be
      reduced, they remain essentially unavoidable. The significant impact of long-term
      complications requires increased awareness and recognition to promote prevention
      and appropriate intervention. It is therefore important for the primary
      oncologist to be aware of these complications so that appropriate measures can be
      implemented in a timely manner. Prevention and management is best provided via
      multidisciplinary health care teams, which must be integrated and communicate
      effectively in order to provide the best patient care in a coordinated manner at
      the appropriate time.

PMID- 22972546
TI  - Do approved doctors and medical referees in the UK agree when assessing a
      seafarer's fitness?
AB  - INTRODUCTION: The seafaring industry remains a hazardous occupation that requires
      sophisticated systems of risk and fitness assessment. This study aims to
      investigate the extent of agreement between Approved Doctors (ADs) and Medical
      Referees (MRs) when they assess a seafarer's fitness. MATERIAL AND METHODS:
      Between 2003 and 2009 a total of 232,878 seafarer medical examinations were
      carried out by ADs, of which 465 were considered by the MRs because the seafarer
      appealed against the AD's decision. The extent of agreement between ADs and MRs
      was studied. RESULTS: Two hundred and sixty-eight (58%) cases seen by the ADs
      were classed as category 4 "permanently unfit"; the referees only placed 85 (18%)
      of them in this category. On the other hand, 252 (54%) cases seen by the MRs were
      classed as category 2 "fit with restrictions", while the ADs had only placed 111
      (24%) in this category. The overall agreement between the assessors (AD vs. MR)
      was poor (Kappa K = 0.18). DISCUSSION: For cardiovascular diseases and for mental
      ill-health, access to additional information by the MR was the commonest reason
      for changing the fitness category, but for all other conditions factors such as
      the experience and knowledge of the MRs or their different interpretation of the
      standards were the most frequent reasons for a change to fitness category or to
      restrictions. CONCLUSIONS: This study found that there was poor agreement between
      the AD's decision and the subsequent MR's decision regarding the fitness of those
      seafarers who decided to appeal against the AD's initial assessment. The reasons
      for this are considered.

PMID- 22972545
TI  - Molecular studies on the roles of Runx2 and Twist1 in regulating FGF signaling.
AB  - BACKGROUND: Supernumerary teeth are often observed in patients suffering from
      cleidocranial dysplasia due to a mutation in Runx2 that results in
      haploinsufficiency. However, the underlying molecular mechanisms are poorly
      defined. In this study, we assessed the roles of Runx2 and its functional
      antagonist Twist1 in regulating fibroblast growth factor (FGF) signaling using in
      vitro biochemical approaches. RESULTS: We showed that Twist1 stimulated Fgfr2 and
      Fgf10 expression in a mesenchymal cell line and that it formed heterodimers with
      ubiquitously expressed E12 (together with E47 encoded by E2A gene) and
      upregulated Fgfr2 and Fgf10 promoter activities in a dental mesenchyme-derived
      cell line. We further demonstrated that the bHLH domain of Twist1 was essential
      for its synergistic activation of Fgfr2 promoter with E12 and that the binding of
      E12 stabilized Twist1 by preventing it from undergoing lysosomal degradation.
      Although Runx2 had no apparent effects on Fgfr2 and Fgf10 promoter activities, it
      inhibited the stimulatory activity of Twist1 on Fgfr2 promoter. CONCLUSIONS:
      These findings suggest that Runx2 haploinsufficiency might result in excessive
      unbound Twist1 that can freely bind to E12 and enhance FGF signaling, thereby
      promoting the formation of extra teeth.

PMID- 22972547
TI  - The mental health of seafarers.
AB  - BACKGROUND: The objectives of this paper are to review published and unpublished
      information on the mental health of seafarers in order to 1) provide a window on
      the current status of seafarers' mental health; 2) establish whether the mental
      health of seafarers in many cases continues to be very poor; 3) describe two
      current projects to improve the mental health of seafarers; and 4) suggest an
      industry-wide effort to improve the mental health of seafarers. MATERIALS AND
      METHODS: A review of recent literature on the mental health of seafarers was
      made, and published statistics covering the years 1960-2009 were obtained. In
      describing seafarers' mental health the use of rates to cite trends in suicides
      by seafarers was not employed. Statistics on seafarer deaths are given by two
      methods as percentages of deaths by suicide by seafarers. One compares deaths by
      suicide to total deaths and the second compares deaths by suicide to deaths due
      to illness. It is felt these methods are more readily understood by non
      scientists who may be in policy-making roles in business or government. A
      detailed description covers two current projects to improve the mental health of
      seafarers. RESULTS: The causes of depression by seafarers are described.
      Statistics from 1960-2009 on the deaths by seafarers compared to total deaths of
      17,026 show 1,011 seafarers died as a result of suicide (5.9%). Compared to
      deaths of 4,487 seafarers due to illness, 590 seafarers died as a result of
      suicide (13.1%). These percentages would be higher if 50% of deaths due to
      seafarers disappearing at sea were included. Based on industry data, in 2012 the
      daily expected costs to operate a 3,000-4,000 TEU container ship are US$7,825,
      and US$10,944 for a 10,000 TEU container ship--not including the cost of fuel
      oil. In 2011 a master who disappeared in waters off Australia may have cost the
      ship owner US$50,000-US$100,000 due to the voyage being diverted and delayed. Two
      projects to improve the mental health of seafarers, one by the Rotary Club of
      Melbourne South and another by the International Committee on Seafarers' Welfare,
      are described. It is estimated that by the end of 2012 about 3,500-4,000 ships in
      17 major Australian ports will have received booklets and leaflets for masters
      and crew members on the sole topic of depression from the Rotary Club of
      Melbourne South's project The Mental Health of Seafarers. RECOMMENDATION FOR
      FURTHER ACTION: A suggestion is made for a shipping industry project that could
      result in all merchant ships worldwide receiving mental health information based
      on the material produced by both the Rotary Club of Melbourne South and the
      International Committee on Seafarers' Welfare. CONCLUSIONS: The data on suicides
      proves that the mental health of seafarers in many cases continues to be very
      poor and often fatal. With deaths aboard merchant ships resulting from depression
      leading to suicide being widely reported, the damage to the seafarers, their
      families, and ship owners cannot be ignored. It strongly demonstrates the need
      for everybody connected with the international maritime shipping industry to do
      something about it. The mental health of seafarers and the economic health of the
      shipping industry will be improved as a result.

PMID- 22972548
TI  - Cultural differences in emotional intelligence among top officers on board
      merchant ships.
AB  - The current research investigated cultural differences in emotional intelligence
      among top officers on board vessels of multicultural maritime companies. We found
      that Southeast Asian officers scored higher than European officers on the total
      Emotional Intelligence scale. When separating the EQ scale in its facets, higher
      scores for Asian officers were found on "Utilization of emotions", "Handling
      relationships", and on "Self-control". Another finding was that Chief
      officers/Second engineers scored higher than Masters/Chief Officers on "Self
      control". Finally, we found a negative correlation between age and scores on the
      facet of "Self-control". These crosscultural differences may have implications
      for interpersonal relations and ship management.

PMID- 22972549
TI  - Why do Filipinos have fewer reported work accidents than other nationals?
      Findings from literature.
AB  - According to statistics, Filipinos working on Danish ships experience fewer work
      accidents than their colleagues. In an ongoing project, we are trying to find out
      what lies behind the figures. The first step of the project is a review of recent
      studies on the relationship between nationality and safety. The reviewed studies
      confirm that there is no reason to believe that employees' ethnic or national
      background determines their safety practice, all things being equal, mainly
      because things are never equal. If we are to believe the reviewed studies, it is
      not the minority or migrant status, as such, which makes employees vulnerable,
      but more likely convergent factors.

PMID- 22972550
TI  - Acute abdominal pain during an Antarctic cruise--a case report.
AB  - A 21-year-old female crew member experienced a number of medical conditions
      during a summer cruise to the Antarctic Peninsula. At one point symptoms and
      signs strongly suggested acute appendicitis. She was monitored and treated
      conservatively on board and recovered uneventfully without surgery. Later she had
      a biliary colic attack and then an allergic reaction to the pain medication
      given. The pre-employment medical fitness certificate cannot always be trusted
      regarding previous history of allergies and medical conditions.

PMID- 22972551
TI  - Stress and fatigue at sea versus quality of life. Gdansk, 11 June 2012. II
      International Congress on Maritime, Tropical, and Hyperbaric Medicine. Venue: on
      board "Scandinavia" ferry, Gdansk-Nynashamn-Gdansk. With supporting funding from
      the ITF Seafarers' Trust.

PMID- 22972552
TI  - Nurse training with simulation: an innovative approach to teach complex
      microsurgery patient care.
AB  - Simulation has become an integral part of education at all levels within the
      medical field. The ability to allow personnel to practice and learn in a safe and
      controlled environment makes it a valuable tool for initial training and
      continued competence verification. An area of specific interest to the
      reconstructive microsurgeon is assurance that the nursing staff has adequate
      training and experience to provide optimum care for microsurgery patients.
      Plastic surgeons in institutions where few microsurgeries are performed face
      challenges teaching nurses how to care for these complex patients. Because no
      standard exists to educate microsurgery nurses, learning often happens by chance
      on-the-job encounters. Outcomes, therefore, may be affected by poor handoffs
      between inexperienced personnel. Our objective is to create a course that
      augments such random clinical experience and teaches the knowledge and skills
      necessary for successful microsurgery through simulated patient scenarios.
      Quality care reviews at our institution served as the foundation to develop an
      accredited nursing course providing clinical training for the care of
      microsurgery patients. The course combined lectures on microsurgery,
      pharmacology, and flap monitoring as well as simulated operating room, surgical
      intensive care unit, postanesthesia care unit, Trauma Bay, and Floor scenarios.
      Evaluation of participants included precourse examination, postcourse
      examination, and a 6-month follow-up. Average test scores were 72% precourse and
      92% postcourse. Educational value, effectiveness of lectures and simulation, and
      overall course quality was rated very high or high by 86% of respondents; 0%
      respondents rated it as low. Six-month follow-up test score average was 88%.
      Learning to care for microsurgery patients should not be left to chance patient
      encounters on the job. Simulation provides a safe, reproducible, and controlled
      clinical experience. Our results show that simulation is a highly rated and
      effective way to teach nurses microsurgery patient care. Simulated patient care
      training should be considered to augment the clinical experience in hospitals
      where microsurgery is performed.

PMID- 22972553
TI  - Precise control of osteogenesis for craniofacial defect repair: the role of
      direct osteoprogenitor contact in BMP-2-based bioprinting.
AB  - BACKGROUND: Success with bone morphogenetic protein-2 (BMP-2) has been widely
      reported in the osseous reconstruction of large calvarial defects. These efforts
      have required enormous doses of BMP-2 and are not sufficiently refined to
      facilitate the detail-oriented repair required for intricate craniofacial
      structures. We have previously shown that inkjet-based bioprinting technologies
      allow for precisely customized low-dose protein patterns to induce spatially
      regulated osteogenesis. Here, we investigate the importance of direct contact
      between bioprinted BMP-2 and the dura mater (a source of osteoprogenitors) in
      mediating calvarial healing. METHODS: Five-millimeter osseous defects were
      trephinated in mouse parietal bones (N=8). Circular acellular dermal matrix (ADM)
      implants were prepared such that 1 semicircle of 1 face per implant was printed
      with BMP-2 bio-ink. These implants were then placed ink-toward (N=3) or ink-away
      (N=5) from the underlying dura mater. After 4 weeks, osteogenesis was assessed in
      each of the 4 possible positions (BMP-2-printed area toward dura, BMP-2-printed
      area away from dura, unprinted area toward dura, and unprinted area away from
      dura) by faxitron. RESULTS: The BMP-2-printed portion of the ADM generated bone
      covering an average of 66.5% of its surface area when it was face-down (printed
      surface directly abutting dura mater). By comparison, the BMP-2-printed portion
      of the ADM generated bone covering an average of only 21.3% of its surface area
      when it was face-up (printed surface away from dura). Similarly, the unprinted
      portion of the ADM generated an average of only 18.6% osseous coverage when face
      down and 18.4% when face-up. CONCLUSIONS: We have previously shown that inkjet
      based bioprinting has the potential to significantly enhance the role of
      regenerative therapies in craniofacial surgery. This technology affords the
      precise control of osteogenesis necessary to reconstruct this region's intricate
      anatomical architecture. In the present study, we demonstrate that direct
      apposition of BMP-2-printed ADM to a source of osteoprogenitor cells (in this
      case dura mater) is necessary for bio-ink-directed osteogenesis to occur. These
      results have important implications for the design of more complex bioprinted
      osseous structures.

PMID- 22972554
TI  - Reliability and differentiation of pelvic floor muscle electromyography
      measurements in healthy volunteers using a new device: the Multiple Array Probe
      Leiden (MAPLe).
AB  - AIMS: A new multiple electrode probe, the Multiple Array Probe Leiden (MAPLe),
      has been developed for biofeedback registration of the individual pelvic floor
      musculature (PFM). The aim was to determine the reliability and differentiation
      of electromyography (EMG) signals measured with the MAPLe in healthy volunteers.
      METHODS: Two hundred twenty nine healthy volunteers not seeking treatment or
      using medication for symptoms of prolapse, lower urinary tract, bowel, pain,
      and/or sexual function related to pelvic floor dysfunction were qualified to
      participate. Subjects were asked to perform five tasks: rest, maximum voluntary
      contractions, endurance, cough, and valsalva. Mean EMG values per electrode were
      registered. Test-retest reliability was assessed using linear mixed model with
      random subject effects. One-way ANOVA tests were performed to detect differences
      between groups. RESULTS: Magnetic resonance imaging (MRI) showed that each of the
      electrodes could be related nearest to the individual muscles. For test-retest,
      the intraclass correlation ranged from 0.53 to 0.91. The MAPLe showed significant
      differences in average EMG values between men and women, and between nulliparous
      and parous, pre- and prostmenpausal women. Significant differences were seen
      between the left and right sides of the pelvic floor. In addition, the activity
      nearest to the individual pelvic floor muscles (external anal sphincter (EAS),
      puborectalis muscle, bulbospongiosus, ischiocavernosus and the pubococcygeus
      muscle) could be determined. CONCLUSIONS: The MAPLe is a reliable instrument
      measuring the EMG signals of the different sides and levels nearest to the pelvic
      floor musculature and is capable to differentiate between men and women,
      nulliparous, parous, pre- and postmenopausal. The findings of this study have
      implications for the diagnosis and treatment of pelvic floor dysfunction in the
      future.

PMID- 22972555
TI  - Acquired coronary disease in children: the role of multimodality imaging.
AB  - Coronary sequelae of Kawasaki disease, post-surgical coronary lesions and cardiac
      allograft vasculopathy are the main causes of acquired coronary pathology in
      childhood. Surveillance and timely recognition of coronary problems in children
      who are at risk of ischemic events are imperative and noninvasive imaging is
      increasingly utilized for these purposes. Herein, we summarize the causes of
      acquired coronary disease in children and discuss the role of various imaging
      techniques that are available to establish the diagnosis and guide management.

PMID- 22972556
TI  - Subclinical atherosclerosis and fetuin-A plasma levels in essential hypertensive
      patients.
AB  - The intima-media thickness (IMT) is considered as a surrogate marker for
      atherosclerotic disease. The aim of this study was to analyze the relationship of
      carotid IMT with fetuin-A in patients with essential hypertension (EH) and normal
      renal function. The plasma levels of fetuin-A, interleukin 6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha) and the biomarker of oxidative stress 8-iso
      PGF2alpha were assayed in samples from 105 untreated EH patients. Carotid IMT
      measurements were also performed. EH was studied overall and after dividing in EH
      with IMT >= and <0.9 mm. All of the biomarkers were significantly different
      between the two subgroups, in particular, the fetuin-A level was lower in the
      patients with an IMT >=0.9 mm. In the overall group, the linear analysis of
      correlation demonstrated that the IMT was significantly inversely correlated with
      the fetuin-A level (r=-0.40, P<0.0001) and directly with TNF-alpha (r=0.39,
      P<0.0001), IL-6 (r=0.38, P<0.0001) and 8-iso-PGF2alpha (r=0.356, P<0.0003). The
      multiple regression analysis performed that assigned IMT as a dependent variable
      showed that fetuin-A (beta=-0.268, P<0.0001) was independently correlated with
      the IMT. Receiver-operator curves demonstrated that fetuin-A levels have a
      predictive power of IMT>0.9 mm (AUC (area under the curve) 0.738, P<0.0001). Our
      results suggest that in EH, fetuin-A is associated with the IMT independently of
      oxidative stress and renal function, thus predicting increases in the IMT.

PMID- 22972557
TI  - Endothelial dysfunction and hypertension in aging.
AB  - Hypertension is one of the common diseases in the elderly. The prevalence of
      hypertension markedly increases with advancing age. Both aging and hypertension
      have a critical role in cardiovascular and cerebrovascular complications.
      Although aging and hypertension, either independently or collectively, impair
      endothelial function, aging and hypertension may have similar cascades for the
      pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an
      important role in regulation of vascular tone. Decrease in NO bioavailability by
      endothelial dysfunction would lead to elevation of blood pressure. An imbalance
      of reduced production of NO or increased production of reactive oxygen species,
      mainly superoxide, may promote endothelial dysfunction. One possible mechanism by
      which the prevalence of hypertension is increased in relation to aging may be
      advancing endothelial dysfunction associated with aging through an increase in
      oxidative stress. In addition, endothelial cell senescence is also involved in
      aging-related endothelial dysfunction. In this review, we focus on recent
      findings and interactions between endothelial function, oxidative stress and
      hypertension in aging.

PMID- 22972558
TI  - Recent-onset systemic lupus erythematosus complicated by acute respiratory
      failure.

PMID- 22972559
TI  - The receptor-dependent LQTA-QSAR: application to a set of trypanothione reductase
      inhibitors.
AB  - A new Receptor-Dependent LQTA-QSAR approach, RD-LQTA-QSAR, is proposed as a new
      4D-QSAR method. It is an evolution of receptor independent LQTA-QSAR. This
      approach uses the free GROMACS package to carry out molecular dynamics
      simulations and generates a conformational ensemble profile for each compound.
      Such an ensemble is used to build molecular interaction field-based QSAR models,
      as in CoMFA. To show the potential of this methodology, a set of 38 phenothiazine
      derivatives that are specific competitive T. cruzi trypanothione reductase
      inhibitors, was chosen. Using a combination of molecular docking and molecular
      dynamics simulations, the binding mode of the phenotiazine derivatives was
      evaluated in a simulated induced fit approach. The ligands alignments were
      performed using both ligand and binding site atoms, enabling unbiased alignment.
      The models obtained were extensively validated by leave-N-out cross-validation
      and y-randomization techniques to test for their robustness and absence of chance
      correlation. The final model presented Q(2) LOO of 0.87 and R2 of 0.92 and a
      suitable external prediction of [Formula: see text]= 0.78. The adapted binding
      site obtained is useful to perform virtual screening and ligand structure-based
      design and the descriptors in the final model can aid in the design new
      inhibitors.

PMID- 22972561
TI  - Systematic assessment of scaffold distances in ChEMBL: prioritization of compound
      data sets for scaffold hopping analysis in virtual screening.
AB  - The evaluation of the scaffold hopping potential of computational methods is of
      high relevance for virtual screening. For benchmark calculations, classes of
      known active compounds are utilized. Ideally, such classes should have a well
      defined content of structurally diverse scaffolds. However, in reported benchmark
      investigations, the choice of activity classes is often difficult to rationalize.
      To provide a compendium of well-characterized test cases for the assessment of
      scaffold hopping potential, structural distances between scaffolds were
      systematically calculated for compound classes available in the ChEMBL database.
      Nearly seven million scaffold pairs were evaluated. On the basis of the global
      scaffold distance distribution, a threshold value for large scaffold distances
      was determined. Compound data sets were ranked based on the proportion of
      scaffold pairs with large distances they contained, taking additional criteria
      into account that are relevant for virtual screening. A set of 50 activity
      classes is provided that represent attractive test cases for scaffold hopping
      analysis and benchmark calculations.

PMID- 22972560
TI  - Mapping of the interaction sites of galanthamine: a quantitative analysis through
      pairwise potentials and quantum chemistry.
AB  - A quantitative analysis of the interaction sites of the anti-Alzheimer drug
      galanthamine with molecular probes (water and benzene molecules) representative
      of its surroundings in the binding site of acetylcholinesterase (AChE) has been
      realized through pairwise potentials calculations and quantum chemistry. This
      strategy allows a full and accurate exploration of the galanthamine potential
      energy surface of interaction. Significantly different results are obtained
      according to the distances of approaches between the various molecular fragments
      and the conformation of the galanthamine N-methyl substituent. The geometry of
      the most relevant complexes has then been fully optimized through MPWB1K/6-31 +
      G(d,p) calculations, final energies being recomputed at the LMP2/aug-cc-pVTZ(-f)
      level of theory. Unexpectedly, galanthamine is found to interact mainly from its
      hydrogen-bond donor groups. Among those, CH groups in the vicinity of the
      ammonium group are prominent. The trends obtained provide rationales to the
      predilection of the equatorial orientation of the galanthamine N-methyl
      substituent for binding to AChE. The analysis of the interaction energies pointed
      out the independence between the various interaction sites and the rigid
      character of galanthamine. The comparison between the cluster calculations and
      the crystallographic observations in galanthamine-AChE co-crystals allows the
      validation of the theoretical methodology. In particular, the positions of
      several water molecules appearing as strongly conserved in galanthamine-AChE co
      crystals are predicted by the calculations. Moreover, the experimental position
      and orientation of lateral chains of functionally important aminoacid residues
      are in close agreement with the ones predicted theoretically. Our study provides
      relevant information for a rational drug design of galanthamine based AChE
      inhibitors.

PMID- 22972562
TI  - Rationale and content of psychenet: the Hamburg Network for Mental Health.
AB  - With the public-funded research and development project psychenet: the Hamburg
      Network for Mental Health (2011-2014), the Federal Ministry of Education and
      Research contributes to strengthening healthcare regions in Germany by
      establishing new trans-sectoral cooperations and implement and evaluate selected
      innovations. More than 60 partners from research, health care, health industry
      and government in the Free and Hanseatic City of Hamburg are promoting innovative
      measures to improve the treatment for mental disorders. The main objective is to
      implement integrated healthcare networks based on evidence for effective
      treatment methods, deriving from high-quality research throughout five
      indications such as psychosis, depression, somatoform and functional syndromes,
      anorexia and bulimia and addiction illnesses in adolescence. Those networks are
      accompanied by additional measures, for example, for improving information and
      education, addressing occupational health or strengthening the participation of
      patients and their families suffering from mental illness.

PMID- 22972563
TI  - Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid
      surgery.
AB  - BACKGROUND: Accurate preoperative assessment of thyroid nodules with fine-needle
      aspiration biopsy (FNAB) continues to be a challenge, often resulting in
      unnecessary diagnostic surgical intervention. The detection of several novel gene
      mutations in differentiated thyroid cancer (DTC) over the last decade has led to
      the diagnostic use of these oncogenic alterations to improve FNAB sensitivity and
      specificity. METHODS AND RESULTS: Thyroid oncogene mutations including BRAF, RAS,
      and RET/PTC are reviewed. The potential benefit of using this panel on fine
      needle aspiration (FNA) cytology samples will be described. CONCLUSION: Our use
      of ''reflexive'' molecular testing demonstrates its clinical value in conjunction
      with FNAB cytology, representing an application of personalized molecular
      medicine to guide appropriate surgical therapy.

PMID- 22972564
TI  - The use of a new, modified Dittmer-Lester spray reagent for phospholipid
      determination by the TLC image analysis technique.
AB  - A new phospholipid-specific spray reagent is described. A new phospholipid
      specific spray reagent, which is a modification of the Dittmer-Lester reagent, is
      described in authors' studies. The difference between these two reagents is in
      the addition of tin (II) chloride to the proposed spray reagent. The use of the
      described spray reagent together with an image analysis technique allows not only
      for qualitative, but also for quantitative, determination of major phospholipid
      classes. Separation of phosphatidylserine (PS), phosphatidylethanolamine (PE) and
      phosphatidylcholine (PC) was conducted on an HPTLC plate with a mixture of
      chloroform, methanol and 25% ammonia solution in a volume ratio of 65:25:4 as
      mobile phase. The calibration curves were linear in the ranges of 5.0-25.0, 1.5
      15.0 and 1.0-20.0 ug/spot for PC, PS and PE, respectively. The use of the new
      spray reagent resulted also in lower limits of detection than the standard
      molybdenum method for the investigated phospholipids. The proposed method was
      used to determine the amount of PS in the dietary supplement 'Session', and of
      PS, PE and PC in biological samples, with good results.

PMID- 22972565
TI  - Enhancing the charge transfer of the counter electrode in dye-sensitized solar
      cells using periodically aligned platinum nanocups.

PMID- 22972566
TI  - Comparison of effects of propofol and ketamine-propofol mixture (ketofol) on
      laryngeal mask airway insertion conditions and hemodynamics in elderly patients:
      a randomized, prospective, double-blind trial.
AB  - PURPOSE: The objective of this study was to compare the effects of ketamine
      propofol mixture (ketofol) and propofol on ProSeal laryngeal mask airway (PLMA)
      insertion conditions and hemodynamics in elderly patients. METHODS: Eighty
      elderly patients, American Society of Anesthesiologists (ASA) physical status I
      and II, were randomly divided into two groups to receive either propofol 0.15
      ml/kg (n = 40), or ketofol (using a 1:1 single-syringe mixture of 5 mg/ml
      ketamine and 5 mg/ml propofol) (n = 40) before induction of anesthesia. Sixty
      seconds after induction, the PLMA was inserted. Heart rate and arterial blood
      pressure (systolic [S] BP) were recorded prior to the induction of anesthesia,
      immediately following induction, immediately after PLMA insertion, and 5 and 10
      min after PLMA insertion. PLMA insertion conditions were scored according to
      mouth opening, swallowing, coughing, head and body motion, laryngospasm, and ease
      of PLMA insertion by the same experienced anesthesiologist, who did not know
      which agents were used. RESULTS: There were no differences in PLMA insertion
      conditions between the groups. The number of patients in need of ephedrine (P =
      0.043) and the total dose of ephedrine (P = 0.022) were significantly lower, and
      apnea duration (P < 0.001) was significantly higher in the ketofol group compared
      with the propofol group. SBP was significantly higher in the ketofol group than
      in the propofol group immediately after PLMA insertion and 5 min after PLMA
      insertion. CONCLUSIONS: The same PLMA insertion conditions were found with
      ketofol and propofol. The number of patients in need of ephedrine and the total
      ephedrine dose were lower and apnea duration was increased in the ketofol group.

PMID- 22972567
TI  - Is inflammation a new risk factor of depression in haemodialysis patients?
AB  - PURPOSE: Prevalence of depression is high in patients with chronic kidney
      disease. Depression is associated with increased mortality and the higher rate of
      suicides in these patients. The aim of the study was to estimate the prevalence
      of depressive symptoms in haemodialyzed patients in Upper Silesia region of
      Poland and the possible role of inflammation in depression development. METHODS:
      Six hundred and ninety-seven haemodialyzed patients from 22 dialysis centres in
      Upper Silesia region of Poland were enrolled into the study. Mean age was 59.1 +/
      0.5 years, and mean time of dialysis treatment was 3.6 +/- 0.2 years. Each
      patient received 21-item Beck Depression Inventory (BDI) questionnaire for
      depression screening. Additional questions considering length of dialysis
      treatment, concomitant diseases and number of days spent in hospitals during the
      last year were also asked. RESULTS: Depressive symptoms were found in 268 (38.6
      %) patients. Patients with depressive symptoms when compared with the patients
      without them tended to have higher C-reactive protein plasma concentration (14.3
      +/- 1.3 vs. 11.1 +/- 0.9 mg/l; p = 0.067) and were more often dialyzed with
      central catheter (27.6 vs. 18.2 %; p = 0.0042). During the last year, patients
      with depressive symptoms spent in hospitals more days than patients without
      depressive symptoms (24.3 vs. 15.3 days, respectively; p < 0.0001). Significant
      positive correlation between BDI score and C-reactive protein level (r = 0.1625;
      p = 0.001) was found both in univariate and multivariate analysis. CONCLUSIONS:
      (1) Depressive symptoms are frequently found (38.6 %) in haemodialyzed patients
      in Upper Silesia part of Poland. (2) Catheter placement and inflammation seem to
      play an important role in the pathogenesis of depression in haemodialysis
      patients.

PMID- 22972568
TI  - The Janus faces of ESAs: caveat Chimaera!
AB  - Patients with chronic kidney disease (CKD) have a Janus quality as they look back
      whence they came in developing CKD and, in some cases, also look forwards to a
      potential kidney transplant with the attendant promise of improvement in quality
      and often quantity of life. Making the most of this often unique opportunity is
      key-maximising the chance that the engraftment starts as a success, and then
      later, preserving good kidney transplant function for as long as possible. Two
      recently published, independently conceived and executed studies are relevant to
      both aspects of this quest and thus to all kidney transplant recipients (KTRs).
      Both trials also simultaneously stoke and quench the continuing, heated debates
      over target haemoglobin (Hb) levels, and the use of erythropoiesis-stimulating
      agents (ESAs), in CKD patients. One study--of acute, high-dose ESA administration
      -adds to the plethora of adverse safety signals swirling around the use of ESAs
      while surprisingly also showing renal function benefits at 12 months. The other
      study features chronic lower-dose ESA use in stable KTRs with anaemia and
      impaired renal function and not only purports to show a salutary effect on 2-year
      renal function outcomes (and thus reducing "return to dialysis" rates), but also
      rebuts the now widely accepted current notion that by chronic use of ESAs to
      target full Hb correction/higher Hb values in anaemic CKD patients, we are
      potentially causing harm.

PMID- 22972569
TI  - Can high-dose-rate brachytherapy prevent the major genitourinary complication
      better than external beam radiation alone for patients with previous
      transurethral resection of prostate?
AB  - PURPOSE: To compare the grade 3 genitourinary toxicity and oncological outcome
      for localized prostate cancer between high-dose-rate (HDR) brachytherapy and
      external beam radiation therapy (EBRT) alone in patients with previously
      undergone Transurethral resection of the prostate (TURP). MATERIALS AND METHODS:
      From November 1998 to November 2008, 78 patients with a history of TURP underwent
      radiation therapy for localized prostate cancer. Of these, 59 were enrolled in
      this study. In this study, 34 patients underwent HDR brachytherapy and 25
      patients underwent EBRT alone. RESULTS: Grade 3 genitourinary complication was
      observed in 8.8 % of HDR brachytherapy group and 44 % in EBRT alone group. Five
      year urinary incontinence rate was 2.9 % in HDR brachytherapy and 24 % in EBRT
      alone group. The results showed that significant higher incidence of grade 3
      genitourinary complication (p = 0.003) and urinary incontinence was the most
      significant (p = 0.023) in the EBRT alone group. Five-year biochemical survival
      rate was 82.4 % in HDR brachytherapy group and 72.0 % in EBRT alone group (p =
      0.396). CONCLUSIONS: In patients with prostate cancer who have previously
      undergone TURP, we observed that HDR brachytherapy was able to control prostate
      cancer with fewer GU morbidities and oncological outcomes that were similar to
      those associated with traditional EBRT alone. Moreover, HDR brachytherapy led to
      a decrease in major GU toxicity and also preserved the sphincter function more
      than that in TURP patients who underwent EBRT alone.

PMID- 22972570
TI  - Uniform moment theory for charged particle motion in gases.
AB  - Moment equations for the motion of trace amounts of charged particles through
      dilute gases are developed from the Boltzmann equation. A new method for
      truncating the coupled moment equations is used to develop differential equations
      governing the moments in successive approximations. The first approximation
      equations are shown to agree completely with equations known to describe ion
      motion in drift-tube mass spectrometers, ion mobility spectrometers, ion traps,
      and collision-dominated ion cyclotron resonance experiments. Applications to
      differential mobility spectrometers and other devices are also described.

PMID- 22972571
TI  - Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica
      in experimental animals.
AB  - This study was aimed to provide pharmacological basis for the medicinal use of
      Phyllanthus emblica fruit in indigestion and constipation using the in-vivo and
      in-vitro assays. The crude extract of the dried fruits of Phyllanthus emblica
      (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins,
      terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300
      mg/kg exhibited the prokinetic and laxative activities in mice, which were found
      partially sensitive to atropine. In isolated guinea-pig ileum and rabbit jejunum,
      the crude extract and its aqueous fraction (Pe.Aq) caused concentration-dependent
      and partially atropine-sensitive stimulatory effects followed by relaxation at
      higher tested concentrations, being more efficacious in guinea pig, while more
      potent in rabbit tissues. The petroleum fraction (0.003-0.1 mg/mL) exhibited
      fully atropine-sensitive contractions in both guinea-pig and rabbit tissues.
      However, the ethyl acetate and chloroform fractions (0.003-1.0 mg/mL) showed only
      spasmolytic activity when studied in spontaneously contracting rabbit jejunum.
      This study showed that the Phyllanthus emblica possesses prokinetic and laxative
      activities in mice along with spasmodic effect in the isolated tissues of guinea
      pig and rabbit, mediated partially through activation of muscarinic receptors;
      thus, this study provides a rationale for the medicinal use of Phyllanthus
      emblica fruits in indigestion and constipation.

PMID- 22972573
TI  - [Clinical variability of polymicrogiria: report of 35 new cases and review of the
      literature].
AB  - INTRODUCTION: The study of polymicrogyria with magnetic resonance imaging (MRI)
      has made possible the report of several series of patients in which the main
      clinical manifestations differ considerably. The aims of the study were to review
      the literature and to know the clinical variability of the patients attended in a
      neuropediatric service. PATIENTS AND METHODS: A retrospective study was conducted
      between 1989-2011 for the patients attended in our neuro-pediatric service and
      diagnosed of polymicrogyria by MRI. RESULTS: On the totality of 44 patients
      having polymicrogyria, 9 did not satisfy de inclusion criteria (Barkovich's
      radiological criteria). The polymicrogyria was bilateral in 22/35 patients (1
      frontal, 22 perisylvian) and unilateral in 13/35 (2 frontal, the rest
      perisylvian). All patients with bilateral polymicrogyria had intellectual
      disability, 71% had global development delay, 75% had oromotor disorder and 40%
      had epilepsy. Patients with unilateral polymicrogyria had the following symptoms:
      65% intellectual disability, 55% global development delay, 55% oromotor disorder,
      55% epilepsy and 2 patients where free of symptoms (the oldest 2 year old). The
      initial symptoms were depending upon the age: the oromotor disorder was the most
      common in the newborn period, global development delay if the symptoms started
      before 2 years old and after 2 years epilepsy was the initial most common
      symptom. CONCLUSION: In our study the most common symptom was intellectual
      disability (independently of the type of poly-microgyria), followed by oromotor
      disorder and, with fewer proportion, epilepsy (in contrast with other series).

PMID- 22972572
TI  - Evidence that BRCA1- or BRCA2-associated cancers are not inevitable.
AB  - Inheriting a BRCA1 or BRCA2 gene mutation can cause a deficiency in repairing
      complex DNA damage. This step leads to genomic instability and probably
      contributes to an inherited predisposition to breast and ovarian cancer. Complex
      DNA damage has been viewed as an integral part of DNA replication before cell
      division. It causes temporary replication blocks, replication fork collapse,
      chromosome breaks and sister chromatid exchanges (SCEs). Chemical modification of
      DNA may also occur spontaneously as a byproduct of normal processes. Pathways
      containing BRCA1 and BRCA2 gene products are essential to repair spontaneous
      complex DNA damage or to carry out SCEs if repair is not possible. This scenario
      creates a theoretical limit that effectively means there are spontaneous BRCA1/2
      associated cancers that cannot be prevented or delayed. However, much evidence
      for high rates of spontaneous DNA mutation is based on measuring SCEs by using
      bromodeoxyuridine (BrdU). Here we find that the routine use of BrdU has probably
      led to overestimating spontaneous DNA damage and SCEs because BrdU is itself a
      mutagen. Evidence based on spontaneous chromosome abnormalities and epidemiologic
      data indicates strong effects from exogenous mutagens and does not support the
      inevitability of cancer in all BRCA1/2 mutation carriers. We therefore remove a
      theoretical argument that has limited efforts to develop chemoprevention
      strategies to delay or prevent cancers in BRCA1/2 mutation carriers.

PMID- 22972574
TI  - [Descriptive analysis of the activity in a movement disorder unit in a tertiary
      hospital in Catalonia].
AB  - INTRODUCTION: Movement disorders are an important part of the activity of a
      Neurology service, but there are few studies examining their health care demand.
      AIMS: To analyze the first visits of the Movement Disorders Unit of the Hospital
      de la Santa Creu i Sant Pau in Barcelona and to compare the results with those of
      previous studies. PATIENTS AND METHODS: Prospective study of the first
      neurological assessments carried out during 2010. Demographic variables of
      patients were collected and diagnoses were reviewed 12 months later. RESULTS: 423
      first visits were done (application rate of 1.41 per 1000 inhabitants-year): 54%
      females, median age 68.8 +/- 14.2 years-old. 74.3% of referrals came from the
      family doctor. The most frequent reasons for consultation were tremor (40%) and
      parkinsonism-motor clumsiness (26%). The most prevalent diagnoses were
      Parkinson's disease (36%) and essential tremor (19%). After the first assessment,
      84% of patients continued controls in the Unit. One year later, in the 8% of
      cases there was a change in the initial diagnosis. Taking into account the
      incidence of each disorder, the number of patients seen was fewer compared to the
      estimated (19.5 times lower), especially marked in cases of restless legs
      syndrome, essential tremor and Tourette syndrome. CONCLUSIONS: In our Unit the
      most frequent reason for consultation is tremor and the most prevalent diagnosis
      is Parkinson's disease. The number of patients treated is clearly lower than the
      estimated according to the incidence of the diseases in the population.

PMID- 22972575
TI  - [Evaluation of the instrumental activities of daily living following a stroke by
      means of the Lawton and Brody scale].
AB  - INTRODUCTION: The instrumental activities of daily living are activities that are
      somewhat more complex than basic activities of daily living, and being able to
      perform them allows a person to be independent within a community. They include
      housework, tasks involving mobility, managing the home and property; catching the
      bus; cooking meals and going shopping, among other things. AIMS: To evaluate
      these activities using the Lawton and Brody scale following an ischaemic stroke
      or intraparenchymatous haemorrhage and to analyse the factors that have an
      influence on the functional status at six months. PATIENTS AND METHODS: We
      conducted a prospective study of patients admitted to the stroke unit between
      September 2010 and June 2011 diagnosed with ischaemic strokes and spontaneous
      intraparenchymatous haemorrhages. A series of clinical and demographic variables
      were collected. In the follow-up visit at six months, the patients were re
      evaluated by measuring their score on the Lawton and Brody scale again. RESULTS:
      The percentages of the Lawton and Brody scale at six months were as follows:
      28.9% of patients were highly dependent, 45.4% were moderately dependent and
      25.6% were dependent. There were differences according to age, severity and the
      type of stroke, and also depending on the presence of aphasia or hemiparesis.
      CONCLUSIONS: Patients who have suffered an ischaemic stroke or haemorrhage
      present a poorer score in instrumental activities of daily living when age is
      more advanced, the stroke is more severe and when aphasia or hemiparesis are
      present.

PMID- 22972576
TI  - [Continuous monitoring of cortical visual evoked potentials by means of subdural
      electrodes in surgery on the posterior optic pathway. A case report and review of
      the literature].
AB  - INTRODUCTION: Intraoperative monitoring of functional language and motor areas is
      a commonly used technique which makes it possible to minimise the post-operative
      sequelae and to perform an optimal resection of lesions in these areas.
      Monitoring of the visual cortex, however, is not usually carried out nowadays.
      The scarce spatial resolution and its sensitivity to anaesthesia are some of the
      technical difficulties that reduce its clinical usefulness. The study reports a
      case of resection of an occipital lesion under general anaesthetic, with
      intraoperative monitoring of the cortical visual evoked potentials (VEP) by means
      of subdural electrodes. CASE REPORT: A 50-year-old female who underwent surgery
      involving the resection of an occipital lesion that was suggestive of
      radionecrosis. The VEP were monitored by administering flashing light at 4.1 Hz
      and recording with subdural strip electrodes on the occipital cortex. During the
      operation, a progressive lowering of the amplitude of the cortical VEP was
      observed when 50% of the baseline amplitude was exceeded, and thus the resection
      was finished. The increase in latency was below 10% of the baseline value. The
      patient recovered well during the post-operative period and her sight did not
      present any changes with respect to the baseline values. CONCLUSIONS: In our
      case, monitoring the cortical VEP by cortical recordings produced stable
      recordings with a good correlation with the post-operative visual function.
      Cortical recordings performed either directly or by means of subdural electrodes
      make it possible to achieve adequate spatial resolution and response intensity.
      Further studies need to be conducted with a greater number of patients in order
      to obtain decisive conclusions.

PMID- 22972577
TI  - [Migraine as a vascular risk factor].
AB  - INTRODUCTION: Migraine and stroke are associated with a higher frequency than
      expected. Numerous studies have shown a significant, but controversial,
      association between migraine and vascular disease, not only in cerebral but also
      in other arterial beds. The full spectrum of this relationship includes
      coexisting stroke and migraine, stroke with clinical features of migraine and
      migraine-induced stroke. Why migraine is a risk factor and how it leads to stroke
      is not entirely understood, possibly because the mechanisms involved are
      multiple, complex and interrelated. AIM: Emphasizing the most recent papers, we
      review critically the current knowledge about the causal relationship between
      migraine and vascular disease and discuss its pathophysiology. DEVELOPMENT:
      Migraine is an independent risk factor for stroke, especially for young women
      with frequent migraine with aura attacks, who smoke and use oral contraceptives.
      Migraine has also been associated with lesions in the white matter and in other
      vascular territories. Potential pathogenic mechanisms include endothelium and
      vascular smooth muscle dysfunction, hypercoagulability, cortical spreading
      depression, genetic factors, patent foramen ovale, unfavourable vascular risk
      profile, arterial dissection and migraine-specific treatment. CONCLUSION:
      Considering that cerebrovascular disease is a major cause of disability and
      mortality and that migraine is a risk factor for vascular disease, understanding
      the relationship between migraine and vascular disease is necessary to reduce
      risks and optimize management and treatment.

PMID- 22972578
TI  - [Clinical use of 30:70 controlled-release methylphenidate in the treatment of
      attention deficit hyperactivity disorder].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most
      frequent reasons for visits in daily clinical practice, with a prevalence rate of
      1-7% in Spain. The effectiveness of stimulants for the treatment of ADHD has been
      widely demonstrated and methylphenidate (MPD) is the most commonly used. There
      are currently several different immediate-release or extended-release
      formulations of MPD on the market. AIMS: To review the characteristics of the
      different formulations of MPD, with special attention paid to the studies on
      Equasym(r), an extended-release preparation soon to be made available in Spain.
      The article also includes recommendations for clinical practice and the choice of
      drugs. DEVELOPMENT: Several studies have assessed the effectiveness of Equasym(r)
      versus placebo or in comparison to other MPD formulations. The extended-release
      preparations have a therapeutic action that is similar to that of the immediate
      release versions, the difference between them being the plasma concentration
      profiles over time during the day, which are reflected in the pharmacodynamic
      effects. Equasym(r) is more effective in the morning, whereas other formulations,
      such as Concerta(r), allow greater control of the symptoms in the afternoon.
      These differences are important when it comes to prescribing the treatment.
      CONCLUSIONS: One of the main advantages of having different formulations of MPD
      available is that it allows the professional to choose the drug that best suits
      the clinical features and needs of each patient. The individual response is the
      essential criterion in deciding on the most appropriate treatment.

PMID- 22972580
TI  - [Vagal cephalalgia: description of a new case report].

PMID- 22972581
TI  - [Multicentre cerebral disorder due to juvenile xanthogranuloma].

PMID- 22972582
TI  - [Respiratory compromise in amyotrophic lateral sclerosis: electromyographic
      evidence].

PMID- 22972583
TI  - [Usefulness of neurosonology in the diagnosis of acute hydrocephalus].

PMID- 22972584
TI  - [Cocaine and cerebral vascular risk].

PMID- 22972585
TI  - Effects of perinatal exposure to low doses of tributyltin chloride on pregnancy
      outcome and postnatal development in mouse offspring.
AB  - Tributyltin (TBT), an endocrine-disrupting chemical, is well known to induce
      imposex in female gastropods. In this study, we assessed the effects of low doses
      of tributyltin chloride (TBTCl) on dams and their offspring. Pregnant mice were
      administered by gavage with 0, 1, 10, or 100 MUg TBTCl/kg body weight/day from
      day 6 of pregnancy through the period of lactation. There were no TBT treatment
      related deaths or clinical signs of toxicity for dams, and no treatment-related
      effects on body weight, litter sizes, gestational length of dams, and sex ratio,
      lactational body weight, postnatal survival, age at eruption of incisors, and eye
      opening of pups. However, at 100 MUg/kg, TBTCl retarded the testes descent of
      male offspring. Behavioral tests showed a significant delay in cliff-drop
      aversion response in offspring of 10 and 100 MUg/kg groups, but no significant
      difference in the righting reflex between control and TBT-exposed offspring was
      detectable. These results indicate that neurobehavioral toxicity seems to be one
      sensitive indicator to assess the risk of low doses of TBT.

PMID- 22972586
TI  - Infectious or noninfectious? Ruptured, thrombosed inflammatory aortic aneurysm
      with spondylolysis.
AB  - Osteolysis of vertebrae due to inflammatory aortic aneurysm is rarely observed.
      However, it is estimated that up to 10 % of infectious aneurysms coexist with
      bone tissue destruction, most commonly the vertebrae. Inflammatory aneurysms with
      no identified infection factor, along with infiltration of adjacent muscle and in
      particular extensive destruction of bone tissue have rarely been described in the
      literature. A case of inflammatory aneurysm with posterior wall rupture and
      inflammatory infiltration of the iliopsoas muscle and spine, together with
      extensive vertebral body destruction, is presented. The aneurysm was successfully
      treated with endovascular aneurysm repair EVAR.

PMID- 22972587
TI  - Assessing the critical period for Rho kinase activity during Drosophila ventral
      furrow formation.
AB  - BACKGROUND: Drosophila ventral furrow formation (VFF), which is the first
      morphogenetic event during embryo development, serves as a model for epithelial
      sheet folding. VFF can be subdivided into five cell shape changes: apical
      membrane flattening, apicobasal nuclear migration, apicobasal cell shortening,
      random apical constriction, and concerted apical constriction. These processes
      are generally believed to be driven by Rho kinase (Rok) activation of myosin II
      to stimulate the constriction of the apical actomyosin network. To test the role
      of Rok and its downstream target myosin II in VFF, timed injections of the Rok
      inhibitor, Y-27632, were performed. RESULTS: Embryos injected with Y-27632 before
      the concerted apical constriction phase of VFF were able to execute apicobasal
      nuclear migration and random apical constriction, but were unable to enter the
      concerted apical constriction phase. Embryos injected with Y-27632 during
      concerted apical constriction reverted to the transition point between random
      apical constriction and concerted apical constriction. Finally, embryos injected
      with Y-27632 upon the initiation of furrow ingression were able to complete VFF.
      CONCLUSIONS: Together these results suggest a critical period for Rok activity
      and presumably myosin II activation during the initiation of the concerted apical
      constriction phase of VFF.

PMID- 22972588
TI  - Responses of Javan Gibbon (Hylobates moloch) groups in submontane forest to
      monthly variation in food availability: evidence for variation on a fine spatial
      scale.
AB  - Primates tend to prefer specific plant foods, and primate home ranges may contain
      only a subset of food species present in an area. Thus, primate feeding
      strategies should be sensitive to the phenology of specific species encountered
      within the home range in addition to responding to larger scale phenomena such as
      seasonal changes in rainfall or temperature. We studied three groups of Javan
      gibbons (Hylobates moloch) in the Gunung Halimun-Salak National Park, Indonesia
      from April 2008 to March 2009 and used general linear mixed models (GLMM) and a
      model selection procedure to investigate the effects of variation in fruit and
      flower availability on gibbon behavior. Preferred foods were defined as foods
      that are overselected relative to their abundance, while important food species
      were those that comprised >5% of feeding time. All important species were also
      preferred. Season and measurements of flower and fruit availability affected
      fruit-feeding time, daily path lengths (DPL), and dietary breadth. Models that
      included the availability of preferred foods as independent variables generally
      showed better explanatory power than models that used overall fruit or flower
      availability. For one group, fruit and preferred fruit abundance had the
      strongest effects on diets and DPL in the models selected, while another group
      was more responsive to changes in flower availability. Temporal variation in
      plant part consumption was not correlated in neighboring groups. Our results
      suggest that fine-scale local factors are important determinants of gibbon
      foraging strategies.

PMID- 22972590
TI  - Diagnosis of delirium in patients under noninvasive ventilation in the intensive
      care unit.

PMID- 22972589
TI  - Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination
      therapy stratified by gene mutations in patients with metastatic melanoma.
AB  - BACKGROUND: The high prevalence of v-raf murine sarcoma viral oncogene homolog B1
      (BRAF) and neuroblastoma v-ras oncogene homolog (NRAS) mutations in melanoma
      provides a strong rationale to test the clinical efficacy of mitogen-activated
      protein kinase kinase (MEK) inhibition in this disease. The authors hypothesized
      that the presence of BRAF or NRAS mutations would correlate with clinical benefit
      among patients who received treatment with combination regimens that included the
      MEK inhibitor selumetinib. METHODS: BRAF and NRAS mutation status was determined
      retrospectively in available tissue specimens from patients with melanoma who
      were enrolled in a phase 1 trial of selumetinib in combination with 1 of 4 drugs
      (dacarbazine, docetaxel, temsirolimus, or erlotinib). The clinical response rate
      and the time to progression (TTP) were assessed as a function of BRAF and NRAS
      mutation status. RESULTS: Among 18 patients analyzed, 9 patients (50%) harbored a
      BRAF mutation (8 had a valine-to-glutamic acid substitution at residue 600
      [V600E]; 1 had an arginine nonsense mutation at residue 603 [R603]), 4 patients
      (22%) harbored an NRAS mutation (2 had a glutamine-to-arginine substitution at
      residue 61 [Q61R], 1 had a glutamine-to-lysine substitution at residue 61 [Q61K],
      and 1 had a glycine-to-lysine substitution at residue 12 [G12S]), and 5 patient
      (28%) had the wild type of both genes. These mutations were mutually exclusive.
      Among the 9 patients who had BRAF mutations, 5 patients (56%) achieved a partial
      response, and 4 patients (44%) achieved stable disease for at least 6 weeks. No
      patient with the wild-type BRAF gene achieved a clinical response (P = .01 vs
      patients with BRAF mutations). The presence of an NRAS mutation did not correlate
      with the clinical response rate. The presence of a BRAF mutation was correlated
      significantly with the TTP in a multivariate model (hazard ratio, 0.22; P = .02
      vs wild-type BRAF). CONCLUSIONS: Higher response rates and longer TTP were
      observed with selumetinib-containing regimens in patients who had tumors that
      harbored a BRAF mutation compared with patients who had wild-type BRAF.

PMID- 22972591
TI  - Tuberculosis in transplantation: diagnosis, prevention, and treatment.
AB  - Tuberculosis should always be taken into consideration as a possible infectious
      complication in transplant recipients. It is more frequent and fatal, and its
      diagnosis, prevention, and treatment are more challenging, in transplanted
      patients, as compared with the general population. Latent infection with M.
      tuberculosis is indirectly diagnosed by assessing the presence of a specific
      adaptive immune response, but depending on the assay used, the informative value
      of immunodiagnostic assays may be limited by the inhibitory action of
      immunosuppressive medication, and the positive predictive value for progression
      toward active tuberculosis is generally low. Diagnosis of active tuberculosis is
      challenging, since symptoms in immunocompromised patients are frequently less
      pronounced and atypical. Finally, treatment of tuberculosis is complicated by
      unpredictable drug interactions, drug-related organ toxicities, and development
      of drug resistance. This review provides an overview of the epidemiological
      characteristics of posttransplant tuberculosis and summarizes current knowledge
      on the prevention, diagnosis, and treatment of tuberculosis in transplant
      recipients.

PMID- 22972592
TI  - Evaluation of test characteristics for outcome measures used in Raynaud's
      phenomenon clinical trials.
AB  - OBJECTIVE: Randomized controlled trials (RCTs) in Raynaud's phenomenon (RP) have
      shown conflicting efficacy data. Also, there is no consensus on the outcome
      measures that should be used. Our objectives were to assess the reliability of
      individual core set measures used in 3 RCTs, evaluate the placebo response for
      individual core set measures, and determine if a composite of individual core set
      measures will decrease the placebo response, which may improve our ability to see
      treatment effects in future trials. METHODS: We analyzed core set measures from
      249 patients in the placebo-treated groups from 3 RCTs. Core set measures
      analyzed included the Raynaud's Condition Score (RCS); patient and physician
      assessment of RP; pain, numbness, and tingling during an RP attack; average
      number of attacks/day; and duration of attacks. Intraclass correlation
      coefficients (ICCs) were calculated during the run-in period to the RCTs.
      RESULTS: ICCs of >=0.70 were observed for the RCS, attack symptoms, and average
      attacks/day. A high placebo response rate was observed for all individual core
      measures except the duration of attacks. For the RCS, the placebo response ranged
      from 56% with >=10% improvement to 19.5% with >=60% improvement. In contrast,
      placebo response rates of 10-20% were observed when several core set measures
      were combined to develop a composite score. CONCLUSION: Outcome measures used in
      RCTs of RP are associated with marked variability. A combination of outcome
      measures is associated with low placebo responses. Future studies are needed to
      assess if a composite score will be able to differentiate placebo from an
      effective agent.

PMID- 22972593
TI  - Construct validity of an instrument to measure neuropathic pain in women with
      bladder pain syndrome.
AB  - AIMS: To determine the construct validity of an instrument to measure neuropathic
      pain in women with bladder pain syndrome (BPS). Our hypothesis is that
      neuropathic, bladder, and bowel pain represent different constructs in women with
      BPS. METHODS: Secondary planned analysis of a prospective cross-sectional study
      of 150 women with BPS. The relationship between neuropathic pain, urinary, and
      bowel symptoms was assessed. RESULTS: The correlation of the total neuropathic
      pain score with total urinary and bowel symptom scores was low to moderate (r =
      0.28-0.49). The correlation of specific neuropathic pain items with bladder and
      bowel pain was also low to moderate (r = 0.12-0.36). Women with neuropathic pain
      had significantly higher scores for urinary urgency, bladder pain, abdominal
      pain, diarrhea, and constipation than women with non-neuropathic pain (all P <
      0.0001). CONCLUSION: Somatosensory neuropathic pain and "visceral" bladder and
      bowel pain represent separate but related constructs in women with BPS.

PMID- 22972594
TI  - Laryngeal leishmaniasis: case report of a rare infection.
AB  - BACKGROUND: We report a case of laryngeal leishmaniasis in a United Kingdom (UK)
      resident who lived in Spain for 5 years. METHODS AND RESULTS: The patient
      presented with a history of hoarseness. He had returned to the UK after spending
      5 years in Spain as a retiree. His past medical history includes chronic
      obstructive pulmonary disease (COPD). Histology of a vocal cord biopsy was
      suggestive of leishmaniasis and polymerase chain reaction (PCR) test was positive
      for Leishmania donovani. His use of steroid inhaler probably contributed to his
      acquiring this extremely unusual infection. He was successfully treated with
      intravenous amphotericin. CONCLUSIONS: Laryngeal leishmaniasis is an extremely
      rare infection and is rarely reported in the UK. The ease of travel ensures that
      many tropical infections may present to UK clinicians.

PMID- 22972595
TI  - Substitution of Val72 residue alters the enantioselectivity and activity of
      Penicillium expansum lipase.
AB  - Error-prone PCR was used to create more active or enantioselective variants of
      Penicillium expansum lipase (PEL). A variant with a valine to glycine
      substitution at residue 72 in the lid structure exhibited higher activity and
      enantioselectivity than those of wild-type PEL. Site-directed saturation
      mutagenesis was used to explore the sequence-function relationship and the
      substitution of Val72 of P. expansum lipase changed both catalytic activity and
      enantioselectivity greatly. The variant V72A, displayed a highest
      enantioselectivity enhanced to about twofold for the resolution of (R, S)
      naproxen (E value increased from 104 to 200.7 for wild-type PEL and V72A variant,
      respectively). In comparison to PEL, the variant V72A showed a remarkable
      increase in specific activity towards p-nitrophenyl palmitate (11- and 4-fold
      increase at 25 and 35  degrees C, respectively) whereas it had a decreased
      thermostability. The results suggest that the enantioselective variant V72A could
      be used for the production of pharmaceutical drugs such as enantiomerically pure
      (S)-naproxen and the residue Val 72 of P. expansum lipase plays a significant
      role in the enantioselectivity and activity of this enantioselective lipase.

PMID- 22972596
TI  - Nanoporous gold channel with attached DNA nanolock for drug screening.

PMID- 22972597
TI  - Intrathecal [6]-gingerol administration alleviates peripherally induced
      neuropathic pain in male Sprague-Dawley rats.
AB  - [6]-Gingerol, a structural analog of capsaicin, is an agonist of the transient
      receptor potential vanilloid 1 channel, which is known to have therapeutic
      properties for the treatment of pain and inflammation. The main objective of this
      study was to determine the central effect of [6]-gingerol on neuropathic pain
      when injected intrathecally at the level of the lumbar spinal cord. [6]-Gingerol
      distribution was evaluated following a 40 mg/kg intraperitoneal injection, and
      the brain-to-plasma and spinal cord-to-plasma ratios (0.73 and 1.7, respectively)
      suggest that [6]-gingerol penetrates well the central nervous system of rats.
      Induction of pain was performed using the sciatic nerve ligation model on rats,
      and a 10-ug intrathecal injections of [6]-gingerol was performed to evaluate its
      central effect. The results suggest a significant decrease of secondary
      mechanical allodynia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p < 0.001)
      and thermal hyperalgesia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p <
      0.01). These promising results illustrate that [6]-gingerol could alleviate
      neuropathic pain by acting centrally at the level of the spinal cord.

PMID- 22972598
TI  - Catechins in neuroAIDS.

PMID- 22972600
TI  - 2012 Colorado alphaherpesvirus latency symposium.

PMID- 22972599
TI  - Translational spatial task and its relationship to HIV-associated neurocognitive
      disorders and apolipoprotein E in HIV-seropositive women.
AB  - HIV-associated neurocognitive disorders (HAND) continue to be a neurological
      complication of HIV infection in the era of combined antiretroviral therapy.
      Hippocampal neurodegeneration and dysfunction occurs as a result of HIV
      infection, but few studies to date have assesses spatial learning and memory
      function in patients with HAND. We used the Memory Island (MI) test to study the
      effects of HIV infection, apolipoprotein E (ApoE) allele status, and cerebral
      spinal fluid (CSF) ApoE protein levels on spatial learning and memory in our
      cohort of Hispanic women. The MI test is a virtual reality-based computer program
      that tests spatial learning and memory and was designed to resemble the Morris
      Water Maze test of hippocampal function widely used in rodent studies. In the
      current study, HIV-seropositive women (n = 20) and controls (n = 16) were
      evaluated with neuropsychological (NP) tests, the MI test, ApoE, and CSF ApoE
      assays. On the MI, the HIV-seropositive group showed significant reduced learning
      and delayed memory performance compared with HIV-seronegative controls. When
      stratified by cognitive performance on NP tests, the HIV-seropositive,
      cognitively impaired group performed worse than HIV-seronegative controls in
      ability to learn and in the delayed memory trial. Interestingly, differences were
      observed in the results obtained by the NP tests and the MI test for epsilon4
      carriers and noncarriers: NP tests showed effects of the epsilon4 allele in HIV
      seronegative women but not HIV-seropositive ones, whereas the converse was true
      for the MI test. Our findings suggest that the MI test is sensitive in detecting
      spatial deficits in HIV-seropositive women and that these deficits may arise
      relatively early in the course of HAND.

PMID- 22972601
TI  - Retrospective dosimetry using OSL of tooth enamel and dental repair materials
      irradiated under wet and dry conditions.
AB  - Following a radiological or nuclear emergency event, there is a need for quick
      and reliable dose estimations of potentially exposed people. In situations where
      dosimeters are not readily available, the dose estimations must be carried out
      using alternative methods. In the present study, the optically stimulated
      luminescence (OSL) properties of tooth enamel and different dental repair
      materials have been examined. Specimens of the materials were exposed to gamma
      and beta radiation in different types of liquid environments to mimic the actual
      irradiation situation in the mouth. Measurements were taken using a Riso TL/OSL
      reader, and irradiations were made using a (90)Sr/(90)Y source and a linear
      accelerator (6 MV photons). Results show that the OSL signal from tooth enamel
      decreases substantially when the enamel is kept in a wet environment. Thus, tooth
      enamel is not reliable for retrospective dose assessment without further studies
      of the phenomenon. Dental repair materials, on the other hand, do not exhibit the
      same effect when exposed to liquids. In addition, dose-response and fading
      measurements of the dental repair materials show promising results, making these
      materials highly interesting for retrospective dosimetry. The minimum detectable
      dose for the dental repair materials has been estimated to be 20-185 mGy.

PMID- 22972602
TI  - Two-stage multilevel en bloc spondylectomy with resection and replacement of the
      aorta.
AB  - OBJECTIVE: We report a case of multilevel spondylectomy in which resection and
      replacement of the adjacent aorta were done. Although spondylectomy is nowadays
      an established technique, no report on a combined aortic resection and
      replacement has been reported so far. METHODS: The case of a 43-year-old man with
      a primary chondrosarcoma of the thoracic spine is presented. The local pathology
      necessitated resection of the aorta. We did a two-stage procedure with resection
      and replacement of the aorta using a heart-lung machine followed by secondary
      tumor resection and spinal reconstruction. RESULTS: The procedure was successful.
      A tumor-free margin was achieved. The patient is free of disease 48 months after
      surgery. CONCLUSION: En bloc spondylectomy in combination with aortic resection
      is feasible and might expand the possibility of producing tumor-free margins in
      special situations.

PMID- 22972603
TI  - Computer-assisted fluoroscopic navigation of percutaneous spinal interventions.
AB  - PURPOSE: Percutaneous spine procedures may occasionally be difficult and subject
      to complications. Navigation using a dynamic reference base (DRB) may ease the
      procedure. Yet, besides other shortcomings, its fixation demands additional
      incisions and thereby defies the percutaneous character of the procedure.
      METHODS: A new concept of atraumatic referencing was invented including a special
      epiDRB. The accuracy of navigated needle placement in soft tissue and bone was
      experimentally scrutinised. Axial and pin-point deviations from the planned
      trajectory were investigated with a CT-based 3D computer system. Clinical
      evaluation in a series of ten patients was also done. RESULTS: The new epiDRB
      proved convenient and reliable. Its fixation to the skin with adhesive foil
      provided a stable reference for navigation that improves the workflow of
      percutaneous interventions, reduces radiation exposure and helps avoid
      complications. CONCLUSIONS: Percutaneous spine interventions can be safely and
      accurately navigated using epiDRB with minimal trauma or radiation exposure and
      without additional skin incisions.

PMID- 22972605
TI  - Dietary flexibility of the brown howler monkey throughout its geographic
      distribution.
AB  - Habitat loss and fragmentation constrain the survival of most forest-living
      mammals, particularly strictly arboreal primates. Because fragment size directly
      affects food availability, primate survival in small fragments may depend on
      dietary flexibility. Here, we review the literature on the diet of 29 wild groups
      of Alouatta guariba clamitans inhabiting forest fragments in Brazil and
      Argentina. We identify general feeding patterns and analyze the influence of
      fragment size and latitude on diet composition. Brown howlers presented a diet
      composed of 402 plant species belonging to 227 genera and 80 families.
      Rarefaction curves suggest that the richness of top food species is similar among
      groups living in larger (>100 ha), medium (11-100 ha) or small (1-10 ha)
      fragments. On average, only 12% of the plant species used as food sources by a
      given group was also consumed by groups from other sites. The shorter the
      distance between sites, the higher the diet similarity among groups. Despite
      their diet flexibility, brown howlers spent >80% of the total feeding records on
      6-24 species belonging to genera such as Ficus, Zanthoxylum, and Eugenia. Leaves
      and fruits were the plant items most consumed (65% and 22% of the total feeding
      records, respectively). Leaf consumption was not affected by fragment size, but
      it was inversely related to latitude, which may be linked to an increase in the
      concentration of secondary metabolites in leaves at higher latitudes. We suggest
      that the ability of brown howlers to exploit a large number of plant food
      species, including native and exotic trees, shrubs, vines, and lianas, is an
      important trait that contributes to their survival in highly fragmented habitats
      along the Atlantic forest. Similar meta-analyses of data from other howler
      species are necessary to test whether such dietary flexibility is a genus-wide
      pattern.

PMID- 22972604
TI  - Tibialis posterior tenosynovitis and associated pes plano valgus in rheumatoid
      arthritis: electromyography, multisegment foot kinematics, and ultrasound
      features.
AB  - OBJECTIVE: To compare electromyographic (EMG), kinematic, kinetic, and ultrasound
      (US) features of pes plano valgus associated with US-confirmed tibialis posterior
      (TP) tenosynovitis in rheumatoid arthritis (RA) and healthy control subjects.
      METHODS: In this cross-sectional study, patients with RA and US-confirmed
      tenosynovitis of TP underwent gait analysis, including 3-dimensional kinematics,
      kinetics, and intramuscular EMG of TP, and findings were compared with a group of
      healthy individuals. The RA group also underwent B mode and power Doppler US
      scanning of the TP tendon to assess and score levels of pathology. RESULTS: Ten
      patients with RA, median (range) disease duration of 3 years (1-18 years), and 5
      control subjects were recruited. Compared to control subjects, the RA patients
      walked slower and presented with moderate levels of foot-related disability. The
      mean +/- SD Disease Activity Score in 28 joints was 4.6 +/- 1.6. Increased
      magnitude of TP activity was recorded in the RA group compared to controls in the
      contact period of stance (P = 0.007), in conjunction with reduced ankle joint
      power (P = 0.005), reduced navicular height in the medial arch (P = 0.023), and
      increased forefoot dorsiflexion (P = 0.027). TP tendon thickening, fluid, and
      power Doppler signal were observed in the majority of patients. CONCLUSION: This
      study has demonstrated, for the first time, increased TP EMG activity in the
      presence of US-confirmed TP tenosynovitis in RA. Altered muscle function occurred
      in conjunction with suboptimal mechanics, moderate levels of tendon pathology,
      and active disease. Targeted therapy may be warranted to reduce inflammation and
      mechanically off-load diseased tendon states.

PMID- 22972606
TI  - Impact of parental HIV/AIDS on children's psychological well-being: a systematic
      review of global literature.
AB  - This review examines the global literature regarding the impact of parental
      HIV/AIDS on children's psychological well-being. Fifty one articles reporting
      quantitative data from a total of 30 studies were retrieved and reviewed.
      Findings were mixed but tended to show that AIDS orphans and vulnerable children
      had poorer psychological well-being in comparison with children from HIV-free
      families or children orphaned by other causes. Limited longitudinal studies
      suggested a negative effect of parental HIV on children's psychological well
      being in an early stage of parental HIV-related illness and such effects
      persisted through the course of parental illness and after parental death. HIV
      related stressful life events, stigma, and poverty were risk factors that might
      aggravate the negative impact of parental HIV/AIDS on children. Individual coping
      skills, trusting relationship with caregivers and social support were suggested
      to protect children against the negative effects of parental HIV/AIDS. This
      review underlines the vulnerability of children affected by HIV/AIDS. Culturally
      and developmentally appropriate evidence-based interventions are urgently needed
      to promote the psychological well-being of children affected by HIV/AIDS. 

PMID- 22972607
TI  - Stent strut breakage using high-pressure balloons for bifurcation stenting and
      subsequent percutaneous pulmonary valve replacement using the Edwards Sapien THV.
AB  - This report describes the use of the Edwards Sapien THV in a patient who had a
      short regurgitant/stenotic homograft with early bifurcation stenoses of the
      pulmonary arteries. A 48-mm AndraStent was positioned in the right pulmonary
      artery-homograft jailing the left pulmonary artery (LPA). To have an unobstructed
      access to the LPA, the stent strut leading to the LPA was broken using high
      pressure balloon. A 23-mm Edwards Sapien THV was positioned in the stented
      homograft just proximal to the LPA origin with resolution of the stenosis and
      regurgitation.

PMID- 22972608
TI  - Oral squamous cell carcinoma arising in background of oral submucous fibrosis: a
      clinicopathologically distinct disease.
AB  - BACKGROUND: Oral cancer is the most common cancer in Indian males and is the
      third most common cancer in Indian females. Tobacco, alcohol, areca nut, and
      human papillomavirus (HPV) are the common etiologic factors. Each of these agents
      follows a unique model of carcinogenesis that leads to a certain distinct
      presentation and behavior. For example, HPV is strongly associated with
      oropharyngeal cancers in younger age and is known to have a better outcome and
      specific histopathologic characteristics. A high incidence of oral submucous
      fibrosis (OSMF) is linked to areca nut (group 1 human carcinogen) chewing in the
      Indian subcontinent. METHODS: We prospectively studied 371 consecutive patients
      with proven squamous cell carcinoma of the oral cavity. Of these, 112 patients
      had oral cancer with OSMF and 259 had oral cancer without OSMF. All patients
      underwent standard management and their clinicopathologic findings were recorded.
      RESULTS: We found that patients of oral cancer with OSMF are younger males with
      better prognostic factors such as better grade of tumor differentiation, lesser
      incidence of nodal metastases, and extracapsular spread. This difference was
      maintained even after matching for stage. We also report that presence of OSMF is
      an independent factor influencing nodal metastases. CONCLUSIONS: Based on these
      findings we propose that oral cancers with OSMF constitute a
      clinicopathologically distinct disease. Since all patients with OSMF had chewed
      areca nut with or without smokeless tobacco, we believe that the differences in
      the 2 groups emanate from differential mechanisms of areca nut carcinogenesis.

PMID- 22972609
TI  - Attempted integration of multiple species of turaco into a mixed-species aviary.
AB  - Mixed-species exhibits offer a variety of benefits but can be challenging to
      maintain due to difficulty in managing interspecific interactions. This is
      particularly true when little has been documented on the behavior of the species
      being mixed. This was the case when we attempted to house three species of turaco
      (family: Musophagidae) together with other species in a walk-through aviary. To
      learn more about the behavior of great blue turacos, violaceous turacos, and
      white-bellied gray go-away birds, we supplemented opportunistic keeper
      observations with systematic data collection on their behavior, location,
      distance from other birds, and visibility to visitors. Keepers reported high
      levels of aggression among turacos, usually initiated by a go-away bird or a
      violaceous turaco. Most aggression occurred during feedings or when pairs were
      defending nest sites. Attempts to reduce aggression by temporarily removing birds
      to holding areas and reintroducing them days later were ineffective. Systematic
      data collection revealed increased social behavior, including aggression, during
      breeding season in the violaceous turacos, as well as greater location fidelity.
      These behavioral cues may be useful in predicting breeding behavior in the
      future. Ultimately, we were only able to house three species of turaco together
      for a short time, and prohibitively high levels of conflict occurred when pairs
      were breeding. We conclude that mixing these three turaco species is challenging
      and may not be the most appropriate housing situation for them, particularly
      during breeding season. However, changes in turaco species composition, sex
      composition, or exhibit design may result in more compatible mixed-turaco species
      groups.

PMID- 22972610
TI  - Developmental tracing of luteinizing hormone beta-subunit gene expression using
      green fluorescent protein transgenic medaka (Oryzias latipes) reveals a putative
      novel developmental function.
AB  - BACKGROUND: Luteinizing hormone (LH) and follicle stimulating hormone (FSH),
      produced in gonadotrope cells in the adenohypophysis are key regulators of
      vertebrate reproduction. The differential regulation of these hormones, however,
      is poorly understood and little is known about gonadotrope embryonic development.
      We developed a stable transgenic line of medaka with the LH beta subunit gene
      (lhb) promotor driving green fluorescent protein (gfp) expression to characterize
      development of LH-producing gonadotropes in whole larvae and histological
      sections. Additionally, developmental and tissue-specific gene expression was
      examined. RESULTS: The lhb gene is maternally expressed during early
      embryogenesis. Transcript levels increase by stage 21 (36 hours post
      fertilization [hpf]) and then decrease during continued larval development.
      Examination of the expression of pituitary marker genes show that LH-producing
      cells are initially localized outside the primordial pituitary, and they were
      localized to the developing gut tube by 32 hpf. At hatching, lhb-GFP is clearly
      detected in the gut epithelium and in the anterior digestive tract. lhb-GFP
      expression later consolidate in the developing pituitary by 2 weeks
      postfertilization. CONCLUSIONS: During embryonic development, lhb is primarily
      expressed outside the central nervous system and pituitary. The novel expression
      of lhb in the embryonic gut suggests that LH has a hitherto unidentified
      developmental function.

PMID- 22972611
TI  - The combination of alisertib, an investigational Aurora kinase A inhibitor, and
      docetaxel promotes cell death and reduces tumor growth in preclinical cell models
      of upper gastrointestinal adenocarcinomas.
AB  - BACKGROUND: Upper gastrointestinal adenocarcinomas (UGCs) respond poorly to
      current chemotherapeutic regimes. The authors and others have previously reported
      frequent Aurora kinase A (AURKA) gene amplification and mRNA and protein
      overexpression in UGCs. The objective of the current study was to determine the
      therapeutic potential of alisertib (MLN8237) alone and in combination with
      docetaxel in UGCs. METHODS: After treatment with alisertib and/or docetaxel,
      clonogenic cell survival, cell cycle analyses, Western blot analyses, and tumor
      xenograft growth assays were carried out to measure cell survival, cell cycle
      progression, apoptotic protein expression, and tumor xenograft volumes,
      respectively. RESULTS: By using the AGS, FLO-1, and OE33 UGC cell lines, which
      have constitutive AURKA overexpression and variable tumor protein 53 (p53)
      status, significantly enhanced inhibition of cancer cell survival was observed
      with alisertib and docetaxel treatment in combination (P < .001), compared with
      single-agent treatments. Cell cycle analyses, after 48 hours of treatment with
      alisertib, produced a significant increase in the percentage of polyploidy in UGC
      cells (P < .01) that was further enhanced by docetaxel (P < .001). In addition,
      an increase in the percentage of cells in sub-G1-phase observed with alisertib (P
      < .01) was significantly enhanced with the combination treatment (P < .001).
      Western blot analysis demonstrated higher induction of cleaved caspase 3 protein
      expression with the combined treatment compared with single-agent treatments. In
      addition, FLO-1 and OE33 cell xenograft models demonstrated enhanced antitumor
      activity for the alisertib and docetaxel combination compared with single-agent
      treatments (P < .001). CONCLUSIONS: The current study demonstrated that alisertib
      combined with docetaxel can mediate a better therapeutic outcome in UGC cell
      lines.

PMID- 22972612
TI  - Preventive therapy for breast cancer.
AB  - Trials with tamoxifen have clearly shown that the risk of developing oestrogen
      receptor-positive breast cancer can be reduced by at least 50 % with prophylactic
      agents. The current challenge is to find new agents which achieve this or better
      efficacy, but with fewer side effects. Recent results indicate that the selective
      estrogen-receptor modulator (SERM) raloxifene has fewer endometrial cancers,
      gynaecologic symptoms, and thromboembolic side effects, but is also slightly less
      efficacious. Results for contralateral tumours in adjuvant trials suggest that
      aromatase inhibitors may be able to prevent up to 70-80 % of ER-positive breast
      cancers, and the MAP3 trial has shown to reduce all invasive breast cancer by 65
      % in the preventive setting. The IBIS-II trial is currently investigating
      anastrozole in healthy postmenopausal women. New agents are needed for receptor
      negative breast cancer and premenopausal women, and several possibilities are
      currently under investigation.

PMID- 22972613
TI  - Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide
      treated rat through up-regulation of heme oxygenase-1.
AB  - Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found
      to exhibit antioxidant and anti-inflammatory activities in several experimental
      animal models. However, the underlying mechanisms remain elusive. In this study,
      we provide experimental evidences that AS dose-dependently inhibited
      lipopolysaccharide (LPS)-induced fever and inflammatory response, including serum
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production, liver
      myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression
      and prostaglandin E2 (PGE2 ) production. Interestingly, AS increased serum IL-10
      level, liver heme oxygenase-1 (HO-1) protein expression and activity.
      Furthermore, we found that the suppressive effects of AS on LPS-induced fever and
      inflammation were reversed by pretreatment with ZnPPIX, a HO-1 activity
      inhibitor. In summary, our results suggest that AS has the antipyretic and anti
      inflammatory effects in LPS-treated rat. These effects could be associated with
      the inhibition of pro-inflammatory mediators, including TNF-alpha and IL-6
      levels, COX-2 expression and PGE2 production, as well as MPO activity, which
      might be mediated by the up-regulation of HO-1.

PMID- 22972614
TI  - In vitro evaluation of TAT-OP1 osteogenic properties and prospects for in vivo
      applications.
AB  - So far, osteogenic protein 1 (OP1) is biotechnologically produced and approved
      for the treatment of human lumbar spine fusion and long bone non-union fractures.
      When combined with the TAT sequence, it has been demonstrated in vitro to be
      easily taken up by PC12 neuronal cells and to acquire its biological activity
      after intracellular refolding. In this study, TAT-OP1 was shown to be a useful
      strategy to efficiently drive denatured OP1 into mouse MC3T3E1 pre-osteoblasts.
      The correct in vitro protein refolding was verified by the activation of the BMP
      cascade, while the osteogenic potential of OP1 was demonstrated by increased
      expression of alkaline phosphatase, osteonectin and osteocalcin.

PMID- 22972615
TI  - Physicochemical and toxicological characteristics of urban aerosols during a
      recent Indonesian biomass burning episode.
AB  - Air particulate matter (PM) samples were collected in Singapore from 21 to 29
      October 2010. During this time period, a severe regional smoke haze episode
      lasted for a few days (21-23 October). Physicochemical and toxicological
      characteristics of both haze and non-haze aerosols were evaluated. The average
      mass concentration of PM2.5 (PM with aerodynamic diameter of <=2.5 MUm) increased
      by a factor of 4 during the smoke haze period (107.2 MUg/m(3)) as compared to
      that during the non-smoke haze period (27.0 MUg/m(3)). The PM2.5 samples were
      analyzed for 16 priority polycyclic aromatic hydrocarbons (PAHs) listed by the
      United States Environmental Protection Agency and 10 transition metals. Out of
      the seven PAHs known as potential or suspected carcinogens, five were found in
      significantly higher levels in smoke haze aerosols as compared to those in the
      background air. Metal concentrations were also found to be higher in haze
      aerosols. Additionally, the toxicological profile of the PM2.5 samples was
      evaluated using a human epithelial lung cell line (A549). Cell viability and
      death counts were measured after a direct exposure of PM2.5 samples to A459 cells
      for a period of 48 h. The percentage of metabolically active cells decreased
      significantly following a direct exposure to PM samples collected during the haze
      period. To provide further insights into the toxicological characteristics of the
      aerosol particles, glutathione levels, as an indirect measure of oxidative stress
      and caspase-3/7 levels as a measure of apoptotic death, were also evaluated.

PMID- 22972616
TI  - Distinctive effects of nano-sized permethrin in the environment.
AB  - Pesticides are an essential tool in integrated pest management. Nanopermethrin
      was prepared by solvent evaporation from an oil-in-water volatile microemulsion.
      The efficacy of the formulated nanopermethrin was tested against Aedes aegypti
      and the results compared to those of regular, microparticular permethrin. The 24
      h LC50 for nanopermethrin and permethrin was found to be 0.0063 and 0.0199 mg/L,
      respectively. The formulated nanopermethrin was tested for toxicity against non
      target organisms. Nanopermethrin did not show antibacterial activity against
      Escherichia coli (ATCC 13534 and 25922) or against Bacillus subtilis.
      Phytotoxicity studies of nanopermethrin to the seeds of Lycopersicum esculentum,
      Cucumis sativus, and Zea mays showed no restraint in root length and germination
      percentage. In the Allium cepa test, regular microparticular permethrin treatment
      of 0.13 mg/L showed a mitotic index (MI) of 46.8% and chromosomal aberration of
      0.6%, which was statistically significant (p < 0.05) compared to control. No
      significant differences were observed in 0.13 mg/L nanopermethrin exposure as
      compared to control (MI of 52.0 and 55.03 % and chromosomal aberration of 0.2 and
      0%, respectively). It was concluded that formulated nanopermethrin can be used as
      a safe and effectual alternative to commercially available permethrin formulation
      in agricultural practices.

PMID- 22972617
TI  - Deposition in St. Mark's Basilica of Venice.
AB  - Atmospheric pollutants may cause damage to monuments and historical buildings.
      Besides air contaminants, soluble salts are also responsible for stone
      deterioration and decay in outdoor and indoor monuments. The problem of how to
      conserve works of arts thus requires a deep knowledge of contaminants'
      concentration and distribution inside buildings. In this work, water-soluble ions
      inside St. Mark's Basilica in Venice were studied, with the aim of understanding
      their principal source and distribution inside the building. With the aid of
      Fourier transform infrared spectroscopy and scanning electron microscopy
      analysis, the interaction between ions and surface's material was also
      investigated. Ion chromatographic analysis of depositions highlighted a large
      amount of "deteriorating agents" such as sulphates and chlorides. A possible
      source in the innermost area of the basilica has been found for formates and
      nitrates. On the contrary, a decrease of chloride, from the entrance to the
      innermost area, has been found, which indicates that the source is outside the
      building. It is emphasized that different contaminants behave differently on
      different material, and the effect of pollution inside churches and monuments is
      not easy to predict. Wood and brick seem to react differently than stone and
      mortar to the damaging action of salts and pollutants. The present work should be
      considered a useful tool for the future preservation of St. Mark's Basilica in
      Venice.

PMID- 22972618
TI  - Pollution characteristics of ambient volatile organic compounds (VOCs) in the
      southeast coastal cities of China.
AB  - With the rapid urbanization, the southeast coastal cities of China are facing
      increasing air pollution in the past decades. Large emissions of VOCs from
      vehicles and petrochemical factories have contributed greatly to the local air
      quality deterioration. Investigating the pollution characteristics of VOCs is of
      great significance to the environmental risk assessment and air quality
      improvement. Ambient VOC samples were collected simultaneously from nine coastal
      cities of southeast China using the Tedlar bags, and were subsequently
      preprocessed and analyzed using a cryogenic preconcentrator and a gas
      chromatography-mass spectrometry system, respectively. VOC compositions, spatial
      distributions, seasonal variations and ozone formation potentials (OPFs) were
      discussed. Results showed that methylene chloride, toluene, isopropyl alcohol and
      n-hexane were most abundant species, and oxygenated compounds, aromatics and
      halogenated hydrocarbons were most abundant chemical classes (62.5-95.6% of
      TVOCs). Both industrial and vehicular exhausts might contribute greatly to the
      VOC emissions. The VOC levels in the southeast coastal cities of China were
      sufficiently high (e.g., 6.5 MUg m(-3) for benzene) to pose a health risk to
      local people. A more serious pollution state was found in the southern cities of
      the study region, while higher VOC levels were usually observed in winter. The
      B/T ratio (0.26 +/- 0.09) was lower than the typical ratio (ca. 0.6) for roadside
      samples, while the B/E (1.6-7.6) and T/E (7.2-26.8) ratios were higher than other
      cities around the world, which indicated a unique emission profile in the study
      region. Besides, analysis on ozone formation potentials (OFPs) indicated that
      toluene was the most important species in ozone production with the
      accountabilities for total OFPs of 22.6 to 59.6%.

PMID- 22972619
TI  - PPM: a side-chain and backbone chemical shift predictor for the assessment of
      protein conformational ensembles.
AB  - The combination of the wide availability of protein backbone and side-chain NMR
      chemical shifts with advances in understanding of their relationship to protein
      structure makes these parameters useful for the assessment of structural-dynamic
      protein models. A new chemical shift predictor (PPM) is introduced, which is
      solely based on physical-chemical contributions to the chemical shifts for both
      the protein backbone and methyl-bearing amino-acid side chains. To explicitly
      account for the effects of protein dynamics on chemical shifts, PPM was directly
      refined against 100 ns long molecular dynamics (MD) simulations of 35 proteins
      with known experimental NMR chemical shifts. It is found that the prediction of
      methyl-proton chemical shifts by PPM from MD ensembles is improved over other
      methods, while backbone Calpha, Cbeta, C', N, and H(N) chemical shifts are
      predicted at an accuracy comparable to the latest generation of chemical shift
      prediction programs. PPM is particularly suitable for the rapid evaluation of
      large protein conformational ensembles on their consistency with experimental NMR
      data and the possible improvement of protein force fields from chemical shifts.

PMID- 22972620
TI  - Prognostic value of CD44 expression in penile squamous cell carcinoma: a pilot
      study.
AB  - BACKGROUND: Several studies have reported on the prognostic value of molecular
      markers for metastasis risk and survival in penile squamous cell carcinoma (SCC)
      patients. The usefulness of CD44 expression as such a marker has been studied in
      different tumors, but not in penile SCC. Our aim was to determine whether CD44
      expression may serve as a prognostic marker for lymph node metastasis and
      survival in penile SCC patients. METHODS: CD44 immunoistochemical expression was
      investigated in tissue specimens from 39 patients with penile SCC. CD44 cell
      positivity, staining intensity and distribution were analyzed and correlated with
      tumor stage, grade, lymph node status and disease-specific survival. RESULTS:
      CD44 expression was detected in epithelial cells of both intratumoral and normal
      tissues with different intensities and staining distributions. In normal tissues
      CD44 protein was mainly detected in cell membranes, whereas in the tumor
      compartments it was found in both the cell membranes and the cytoplasm. The
      intensities and percentages of CD44 expressing cells did not correlate with tumor
      stage and/or grade. Seventy-three percent of the patients with lymph node
      metastasis showed high intensities of CD44 staining, as compared to 44% of the
      patients without lymph node metastasis (P = 0.03). Lymph node-positive patients
      showed both cytoplasmic and membranous CD44 expression. High CD44 expression was
      found to be significantly correlated with a decreased 5 year overall survival (P
      = 0.01). CONCLUSIONS: CD44 levels and patterns of expression can be considered as
      markers for penile SCC aggressiveness and, in addition, may serve as predictive
      markers for lymph node metastasis, also in patients with clinically negative
      lymph nodes. CD44 expression may provide prognostic information for penile SCC
      patients, next to classical clinical-pathological factors.

PMID- 22972621
TI  - Endogenous female reproductive hormones and the risk of amyotrophic lateral
      sclerosis.
AB  - The pathogenesis of amyotrophic lateral sclerosis (ALS) is considered to be
      multifactorial. Several epidemiological studies showed a lower incidence of ALS
      in women than in men. This suggests a possible protective effect of female
      reproductive hormones. The aim of this study was to investigate the association
      between female reproductive hormones and ALS. We performed a population-based,
      case-control study in the Netherlands between 1st January 2006 and 1st December
      2009. Only women with a natural menopause were included in the analysis. A total
      of 209 (85 %) of 246 female patients and 672 (93 %) of 719 controls returned a
      questionnaire on reproductive history to calculate the reproductive time-span and
      lifetime endogenous estrogen exposure (calculated by subtracting the duration of
      pregnancies and of oral contraceptive use, and the number of post-ovulatory weeks
      from the reproductive time-span). 131 (63 %) patients and 430 (64 %) age-matched,
      population-based controls had experienced a natural menopause. Multivariate
      analysis showed that increasing the reproductive time-span by a year decreases
      the risk of ALS with an OR of 0.95 (p = 0.005). Each year longer reproductive
      time-span [HR 0.90 (p = 0.01)] and lifetime endogenous estrogen exposure [HR 0.96
      (p = 0.025)] were associated with a longer survival of ALS patients. The positive
      association of a longer reproductive time-span and susceptibility and survival of
      ALS might imply that longer exposure to female reproductive hormones has a
      neuroprotective effect on motor neurons.

PMID- 22972622
TI  - Evidence in court: witness preparation and cross-examination style effects on
      adult witness accuracy.
AB  - Witnesses play a clear and pivotal role in the criminal justice system and there
      is an obvious public interest in identifying procedures that both undermine and
      maximize the quality of evidence received by the criminal courts. This paper
      reports an investigation into the effects of witness familiarization and cross
      examination type on adult witness accuracy that situates outcomes in both legal
      and psychological context. 60 mock witnesses observed a crime event and each
      witness was then cross-examined by a practising barrister in a moot courtroom
      according to two conditions - either via a scripted complex version of cross
      examination or by a simpler but equivalent scripted examination. Mock witnesses
      were also allocated to two further conditions - half the participants received a
      guidance booklet on cross-examination and the other half received no
      familiarization to the process. Study outcomes showed that familiarization of
      witnesses to cross-examination processes increased accurate responses and reduced
      errors. The guidance seemingly allowed accessibility to cognitive information
      that enabled witnesses to process information more effectively. On this basis,
      advance written information about the nature of the cross-examination and
      potentially misleading tactics used by advocates could help to immunize against
      negative lawyerly influence.

PMID- 22972623
TI  - Validated swallowing and nutrition guidelines for patients with head and neck
      cancer: identification of high-risk patients for proactive gastrostomy.
AB  - BACKGROUND: The "Swallowing and Nutrition Guidelines for Patients with Head and
      Neck Cancer" were developed to guide early identification and management of
      dysphagia and nutritional risk before, during, and after cancer treatment. The
      purpose of this study was to validate these guidelines. METHODS: Patients
      attending a Combined Head and Neck Clinic at a major tertiary hospital in 2007 to
      2008 were assessed using the guidelines, with high-risk category patients
      recommended for proactive gastrostomy. Data were collected on guideline
      adherence, gastrostomy tube insertion, and weight. Sensitivity, specificity, and
      positive predictive value were calculated for validation. RESULTS: Proactive
      gastrostomy tubes were inserted in 173 of 501 patients (25%). Overall guideline
      adherence was 87%. High-risk category adherence was 75%. Validation outcomes were
      sensitivity 54%, specificity 93%, and positive predictive value 82%. CONCLUSION:
      The risk categories in the guidelines are valid to assist early identification of
      swallowing and nutritional risk and guide decision-making on proactive
      gastrostomy tube insertion.

PMID- 22972624
TI  - Physico-chemical characterization and biological evaluation of two fibroin
      materials.
AB  - Silk fibroin fibres from two different sources, Bombyx mori pure-breed silkworms
      and polyhybrid cross-bred silkworm cocoons, were treated with formic acid under
      planar stirring conditions to prepare non-woven nets. The treatment partially
      dissolved the fibres, which bound together and formed a non-woven micrometric net
      with fibres coated by a thin layer of low molecular weight fibroin matrix. The
      starting fibres, net materials and fibroin coating layer were characterized in
      terms of amino acid composition, molecular weight and calorimetric properties. In
      vitro cell culture tests with rat fibroblasts were performed to investigate cell
      proliferation, morphology and spreading. Moreover, host-rat fibroblasts were
      preseeded on the afore-mentioned nets and implanted in the thorax of rats for
      histological analysis. In spite of the chemical differences between the two
      starting fibroins, the response of the said materials in vitro and in vivo were
      very similar. These results suggest that the outcome is likely correlated with
      the modification of the processing technique; that during the formation of the
      net, a thin gel layer of similar amino acid composition was formed on the fibroin
      fibres.

PMID- 22972625
TI  - Auditory memory in monkeys: costs and benefits of proactive interference.
AB  - Proactive interference (PI) has traditionally been understood as an adverse
      consequence of stimulus repetition during memory tasks. Herein, we present data
      that emphasize costs as well as benefits of PI for monkeys performing an auditory
      delayed matching-to-sample (DMTS) task. The animals made same/different judgments
      for a variety of simple and complex sounds separated by a 5-s memory delay. Each
      session used a stimulus set that included eight sounds; thus, each sound was
      repeated multiple times per session for match trials and for nonmatch trials as
      the sample (Cue 1) or test (Cue 2) stimulus. For nonmatch trials, performance was
      substantially diminished when the test stimulus had been previously presented on
      a recent trial. However, when the sample stimulus had been recently presented,
      performance was significantly improved. We also observed a marginal performance
      benefit when stimuli for match trials had been recently presented. The costs of
      PI for nonmatch test stimuli were greater than the combined benefits of PI for
      nonmatch sample stimuli and match trials, indicating that the net influence of PI
      is detrimental. For all three manifestations of PI, the effects are shown to
      extend beyond the immediately subsequent trial. Our data suggest that PI in
      auditory DMTS is best understood as an enduring influence that can be both
      detrimental and beneficial to memory-task performance.

PMID- 22972626
TI  - Molecular profiling of synovial joints: use of microarray analysis to identify
      factors that direct the development of the knee and elbow.
AB  - BACKGROUND: Synovial joints develop from the interzone, a dense layer of
      mesenchymal progenitor cells that marks the site of the future joint. During the
      morphogenic events that follow, joints attain their distinct shape and
      organization. The molecular mechanisms controlling the initial specification of
      synovial joints has been studied, but the question of how individual joints
      attain the specific structure required for their unique functions remains largely
      unresolved. Here, we use microarray analysis to compare knee and elbow formation
      to identify factors involved in the development of specific joints. RESULTS: The
      knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and
      for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor
      beta/bone morphogenetic protein (TGFbeta/BMP) and Wnt signaling. Consistent with
      these findings, we show that TGFbeta signaling directs knee morphogenesis, and is
      necessary for meniscus development. The tissue surrounding the elbow is highly
      enriched for genes involved in muscle specification and differentiation, and in
      splotch-delayed muscleless mutants, elbow, but not knee morphogenesis is
      disrupted. CONCLUSIONS: Our results suggest there are fundamental differences in
      how individual joints develop after interzone formation. Our microarray analyses
      provides a new resource for further investigation of the pathways involved in the
      morphogenesis of specific synovial joints.

PMID- 22972627
TI  - In vitro cytotoxicity assessment of ulvan, a polysaccharide extracted from green
      algae.
AB  - Sustainable exploitation and valorization of natural marine resources represents
      a highly interesting platform for the development of novel biomaterials, with
      both economic and environmental benefits. In this context, toxicity data is
      regarded as a crucial and fundamental knowledge prior to any advances in the
      application development of natural derived polymers. In the present work,
      cytotoxicity of ulvan extracted from green algae Ulva lactuca was assessed by
      means of standard in vitro cytotoxicity assays. Fibroblast-like cells were
      incubated in the presence of this green algae's polysaccharide, and cell
      viability was assayed through 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium test. In addition, double
      stranded DNA and total protein were quantified in order to assess cell number. In
      order to establish ulvan's non-cytotoxic behaviour, the effect of this
      polysaccharide on cellular metabolic activity and cell number was directly
      compared to hyaluronic acid (HA), used as a non-cytotoxic control material. In
      this study, ulvan demonstrated promising results in terms of cytotoxicity,
      comparable to the currently used HA, which suggests that ulvan can be considered
      as non-toxic in the range of concentrations studied.

PMID- 22972628
TI  - KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting
      clinical outcomes of cetuximab in metastatic colorectal cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The authors conducted a systematic review and meta-analysis to
      examine whether patients who had metastatic colorectal cancer (mCRC) with the v
      Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an
      amino acid substitution at position 13 in KRAS from a glycine to an aspartic
      acid) and received cetuximab treatment had better clinical outcomes than patients
      who had mCRC tumors with KRAS codon 12 mutations. METHODS: Relevant studies were
      identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and
      Wan Fang Digital Journals from inception to October 2011. The primary clinical
      outcomes included the objective response rate (ORR), progression-free survival
      (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio
      (HR) was estimated by using fixed-effects or random-effects models according to
      heterogeneity between studies. RESULTS: Ten studies were considered eligible that
      included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D
      mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence
      interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81),
      and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors
      with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type
      tumors, patients with the p.G13D mutation had a significantly lower ORR (9
      studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1
      study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66
      1.54). CONCLUSIONS: Patients who had mCRC with the KRAS p.G13D mutation appeared
      to benefit more from cetuximab than patients who had tumors with KRAS codon 12
      mutations. However, because of the limited sample sizes in the current meta
      analysis, these results should be interpreted with caution.

PMID- 22972629
TI  - Unprotected left main bifurcation restenosis treated with a 2-stent technique.
AB  - The present case report refers to the percutaneous treatment of severe left main
      stem stenosis as a consequence of proliferative in-stent restenosis of left
      circumflex coronary with retrograde involvement. A reverse mini-crush technique
      with 2 stents was described.

PMID- 22972630
TI  - New phenolic compounds from Camellia sinensis L. fermented leaves.
AB  - Two new phenolic compounds (1 and 2, named as teasperol and teasperin,
      respectively) were isolated from fermented tea (Camellia sinensis L.) products,
      together with known phenolic compounds. Teasperol (1) was isolated from Chinese
      traditional post-fermented tea leaves (Liu-pao tea) and teasperin (2) was from a
      Japanese tea product which was selectively fermented with Aspergillus sp. The
      chemical structures of 1 and 2 were elucidated based on the analyses of their
      spectroscopic data.

PMID- 22972631
TI  - Speed has an effect on multiple-object tracking independently of the number of
      close encounters between targets and distractors.
AB  - Multiple-object tracking (MOT) studies have shown that tracking ability declines
      as object speed increases. However, this might be attributed solely to the
      increased number of times that target and distractor objects usually pass close
      to each other ("close encounters") when speed is increased, resulting in more
      target-distractor confusions. The present study investigates whether speed itself
      affects MOT ability by using displays in which the number of close encounters is
      held constant across speeds. Observers viewed several pairs of disks, and each
      pair rotated about the pair's midpoint and, also, about the center of the display
      at varying speeds. Results showed that even with the number of close encounters
      held constant across speeds, increased speed impairs tracking performance, and
      the effect of speed is greater when the number of targets to be tracked is large.
      Moreover, neither the effect of number of distractors nor the effect of target
      distractor distance was dependent on speed, when speed was isolated from the
      typical concomitant increase in close encounters. These results imply that
      increased speed does not impair tracking solely by increasing close encounters.
      Rather, they support the view that speed affects MOT capacity by requiring more
      attentional resources to track at higher speeds.

PMID- 22972632
TI  - Salient material properties and haptic volume perception: the influences of
      surface texture, thermal conductivity, and compliance.
AB  - We investigated the influences of surface texture, thermal conductivity, and
      compliance on the haptic perception of the volume of small cubes. It was
      hypothesized that an object containing highly salient material properties would
      be perceived as larger in volume than the same object without these properties.
      Blindfolded subjects were asked to explore pairs of cubes differing in their
      material properties and to select the one with the larger volume. The results
      showed that, counterintuitively, a smooth cube was perceived as being
      significantly larger than a rough cube of the same physical volume, with average
      biases of about 19 %. Furthermore, cubes with a higher thermal conductivity were
      perceived as significantly larger than cubes with a lower thermal conductivity
      (average bias of about 7 %). In addition, the magnitude of the bias in this
      condition was not changed by increasing or decreasing the temperature of the test
      objects, suggesting that the effect of thermal conductivity could not be
      attributed directly to the heat flow. Finally, a hard cube was perceived as
      significantly larger than a soft cube of equal physical volume, with an average
      bias of about 25 %. These results reveal that the studied material properties
      have significant and consistent influences on the haptic perception of volume.
      The observed biases provide an indication of the levels at which the processing
      of haptic information on volume and material properties occurs.

PMID- 22972633
TI  - Circulatory characteristics of normovolemia and normotension therapy after
      subarachnoid hemorrhage, focusing on pulmonary edema.
AB  - BACKGROUND AND PURPOSE: Cardiopulmonary complications are common after
      subarachnoid hemorrhage (SAH), and include pulmonary edema (PE). The purpose of
      this study was to investigate circulatory characteristics of normovolemia and
      normotension therapy after SAH using pulse contour analysis, and to reveal the
      mechanisms of PE after SAH. METHODS: Pulse contour analysis was performed from
      day 3 until day 12 after the onset of SAH in 49 patients. RESULTS: Global end
      diastolic volume index (GEDI) was normal, although net water balance was
      estimated to be negative and central venous pressure (CVP) was low in all
      patients. Seven patients (14 %) suffered from pulmonary edema. Cardiac function
      index (CFI) and global ejection fraction (GEF) were lower in patients with
      pulmonary edema (PE group) than in patients without PE (non-PE group) throughout
      the study period (CFI, P<=0.0119; GEF, P<=0.0348). The PE group showed higher
      GEDI from days 7 to 10, and higher extravascular lung water index (ELWI)
      throughout the entire study period compared to the non-PE group (GEDI, P<=0.0094;
      ELWI, P<=0.0077). CONCLUSIONS: The appropriate preload was kept despite negative
      net water balance and low CVP. PE after SAH was biphasic, with cardiogenic PE
      caused by low cardiac contractility immediately after SAH, and hydrostatic PE
      caused by low cardiac contractility and hypervolemia on and after day 7 of SAH.
      Pulse contour analysis was useful to monitor this unique circulatory change and
      effective for detecting cardiopulmonary complications after SAH.

PMID- 22972634
TI  - Readability assessment of online thyroid surgery patient education materials.
AB  - BACKGROUND: Published guidelines recommend written health information be written
      at or below the sixth-grade level. We evaluate the readability of online
      materials related to thyroid surgery. METHODS: Thyroid surgery materials were
      evaluated using Flesch Reading Ease Score (FRES), Flesch Kincaid Grade Level
      (FKGL), Gunning Frequency of Gobbledygook (GFOG), and Simple Measure of
      Gobbledygook (SMOG). RESULTS: Thirty-one documents were evaluated. FRES scores
      ranged from 29.3 to 67.8 (possible range = 0 to 100), and averaged 50.5. FKGL
      ranged from 6.9 to 14.9 (possible range = 3 to 12), and averaged 10.4. SMOG
      scores ranged from 11.8 to 14.5 (possible range = 3 to 19), and averaged 13.0.
      GFOG scores ranged from 10.6 to 18.0 (possible range = 3 to 19), and averaged
      13.5. CONCLUSIONS: Readability scores for online thyroid surgery materials are
      higher (i.e., more difficult) than the recommended levels. However, readability
      is only one aspect of comprehension. Written information should be designed with
      that fact in mind.

PMID- 22972636
TI  - Predicting positivity for a new era of Alzheimer disease prevention trials.

PMID- 22972637
TI  - Visual resting-state network in relapsing-remitting MS with and without previous
      optic neuritis.
AB  - OBJECTIVE: To investigate functional connectivity of the visual resting-state
      network (V-RSN) in normal-sighted relapsing-remitting multiple sclerosis (RRMS)
      patients with and without previous optic neuritis (ON). METHODS: Thirty normal
      sighted RRMS patients, 16 without (nON-MS) and 14 with (ON-MS) previous ON, and
      15 age- and sex-matched healthy controls (HCs) underwent a neuro-ophthalmologic
      evaluation, including automated perimetry and retinal nerve fiber layer (RNFL)
      measurement, as well as an MRI protocol, including structural and resting-state
      fMRI (RS-fMRI) sequences. Functional connectivity of the V-RSN was evaluated by
      independent component analysis (ICA). Regional gray matter atrophy was assessed
      by voxel-based morphometry (VBM). A correlation analysis was performed between RS
      fMRI results and clinical, neuro-ophthalmologic, and structural MRI variables.
      RESULTS: Compared to HCs, patients with RRMS showed a reduced functional
      connectivity in the peristriate visual cortex, bilaterally. Compared to nON-MS,
      ON-MS patients revealed a region of stronger functional connectivity in the
      extrastriate cortex, at the level of right lateral middle occipital gyrus, as
      well as a region of reduced functional connectivity at the level of right
      inferior peristriate cortex. These latter changes correlated with the number of
      previous ON. All detected V-RSN changes did not colocalize with regional gray
      matter atrophy. CONCLUSIONS: Normal-sighted RRMS patients show a significant
      functional disconnection in the V-RSN. RRMS patients recovered from a previous ON
      show a complex reorganization of the V-RSN, including an increased functional
      connectivity at the level of extrastriate visual areas.

PMID- 22972638
TI  - SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral
      sclerosis.
AB  - OBJECTIVE: There is increasing evidence that common genetic risk factors underlie
      frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS).
      Recently, mutations in the sequestosome 1 (SQSTM1) gene, which encodes p62
      protein, have been reported in patients with ALS. P62 is a multifunctional
      adapter protein mainly involved in selective autophagy, oxidative stress
      response, and cell signaling pathways. The purpose of our study was to evaluate
      the frequency of SQSTM1 mutations in a dataset of unrelated patients with FTLD or
      ALS, in comparison with healthy controls and patients with Paget disease of bone
      (PDB). METHODS: Promoter region and all exons of SQSTM1 were sequenced in a large
      group of subjects, including patients with FTLD or ALS, healthy controls, and
      patients with PDB. The clinical characteristics of patients with FTLD or ALS with
      gene mutations were examined. RESULTS: We identified 6 missense mutations in the
      coding region of SQSTM1 in patients with either FTLD or ALS, none of which were
      found in healthy controls or patients with PDB. In silico analysis suggested a
      pathogenetic role for these mutations. Furthermore, 7 novel noncoding SQSTM1
      variants were found in patients with FTLD and patients with ALS, including 4
      variations in the promoter region. CONCLUSIONS: SQSTM1 mutations are present in
      patients with FTLD and patients with ALS. Additional studies are warranted in
      order to better investigate the role of p62 in the pathogenesis of both FTLD and
      ALS.

PMID- 22972640
TI  - Meningococcal meningitis, dexamethasone, and Class III evidence.

PMID- 22972639
TI  - Association of cognitive dysfunction with neurocirculatory abnormalities in early
      Parkinson disease.
AB  - OBJECTIVE: Cognitive impairment and neurocirculatory abnormalities such as
      orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease
      blood pressure at night (nondipping) occur relatively commonly in Parkinson
      disease (PD); however, whether cognitive dysfunction in early PD is related to
      neurocirculatory abnormalities has not been established. Cognitive dysfunction in
      PD is associated with white matter hyperintensities on MRI. We report results of
      an analysis of neuropsychological and hemodynamic parameters in patients with
      early PD. METHODS: Among 87 patients, 25 had normal cognition, 48 had mild
      cognitive impairment, and 14 had dementia, based on comprehensive
      neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood
      pressure monitoring were recorded, and brain magnetic resonance scans were
      obtained for all patients. RESULTS: Cognitive impairment was associated with OH,
      SH, and white matter hyperintensities but not with nondipping. Dementia and white
      matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one
      had mild cognitive impairment or dementia. CONCLUSIONS: Cognitive dysfunction is
      related to neurocirculatory abnormalities, especially OH + SH, in early PD,
      raising the possibility that early detection and effective treatment of those
      abnormalities might slow the rate of cognitive decline.

PMID- 22972641
TI  - Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a
      prospective cohort study.
AB  - OBJECTIVES: Increasing evidence suggests that uncontrolled seizures have
      deleterious effects on cognition and behavior, particularly in the developing
      brain. METHODS: In a community-based cohort, 198 children, aged <8 years with new
      onset epilepsy were followed prospectively and reassessed with the Wechsler
      Intelligence Scales for Children, Third Edition (WISC-III) 8-9 years later.
      Linear regression analyses with interactions between age at onset (age) and
      pharmacoresistance (PR) were used to test whether earlier onset conveyed greater
      vulnerability to the effects of uncontrolled seizures. Full-scale IQ (FSIQ) and
      the 4 subdomain scores were examined. Adjustment for adaptive behavior scores in
      a subset was performed. A dichotomous indicator for IQ <80 or >=80 was used to
      permit inclusion of children who were not tested, particularly those who were
      untestable. RESULTS: FSIQ was not correlated with age. PR was associated with an
      11.4 point lower FSIQ (p = 0.002) and similar decrements in each WISC-III domain.
      There were substantial age-PR interactions for FSIQ (p = 0.003) and 3 domain
      scores, indicating a lessening impact of PR with increasing age. The dichotomous
      IQ indicator was strongly correlated with age at onset in the pharmacoresistant
      group (p < 0.0001) and not in the non-pharmacoresistant group (p = 0.61).
      Adjustment for adaptive behavior measured near onset did not alter the
      conclusions. CONCLUSIONS: Uncontrolled seizures impair cognitive function with
      effects being most severe in infancy and lessening with increasing age at onset.
      These findings further emphasize the need for early aggressive treatment and
      seizure control in infants and young children.

PMID- 22972642
TI  - Before the headache: infant colic as an early life expression of migraine.
AB  - OBJECTIVE: Childhood periodic syndromes are thought to be early life expressions
      of the genetic tendency for migraine. The objective of this study was to
      determine whether maternal migraine is associated with an increased risk of
      infant colic, because this may indicate that colic is a childhood periodic
      syndrome. METHODS: This was a cross-sectional study performed in general
      pediatric clinics. To minimize recall bias, mothers were surveyed at their
      infants' 2-month-old well-child visit, the age when colic is most prevalent.
      Colic was ascertained via parental report using modified Wessel criteria.
      Migraine history was obtained by having a physician diagnosis or a positive
      screen on ID Migraine. The primary outcome measure was difference in colic
      prevalence in infants with and without a maternal history of migraine. RESULTS:
      Data from 154 infant-mother pairs were analyzed. Infants with a maternal history
      of migraine were 2.6 times as likely to have colic as infants without a maternal
      history of migraine (29% vs 11%, prevalence ratio 2.6 (95% confidence interval
      1.2-5.5), p = 0.02). There was no difference in the accuracy with which
      migraineur mothers perceived their infants' colic status compared with that of
      nonmigraineur mothers. Data on paternal history of migraine were available for 93
      infants. Infants with a paternal history of migraine may have a higher prevalence
      of colic (22% vs 10%), although the prevalence ratio 2.3 (0.6-9.4, p = 0.24) had
      wide confidence intervals. CONCLUSIONS: Maternal migraine is associated with
      increased risk of infant colic. Because migraine has a strong genetic
      underpinning, this association suggests that colic may be an early life
      manifestation of migraine.

PMID- 22972643
TI  - Amyotrophic lateral sclerosis, frontotemporal lobar dementia, and p62: a
      functional convergence?

PMID- 22972644
TI  - Indicators of amyloid burden in a population-based study of cognitively normal
      elderly.
AB  - OBJECTIVES: Secondary prevention trials in subjects with preclinical Alzheimer
      disease may require documentation of brain amyloidosis. The identification of
      inexpensive and noninvasive screening variables that can identify individuals who
      have significant amyloid accumulation would reduce screening costs. METHODS: A
      total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the
      population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B
      (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE
      genotype, family history, or cognitive performance was associated with odds of a
      PiB retention ratio >1.4 and >1.5. Area under the receiver operating
      characteristic curve (AUROC) evaluated the discrimination between PiB-positive
      and -negative subjects. For each characteristic, we determined the number needed
      to screen in each age group (70-79 and 80-89) to identify 100 participants with
      PiB >1.4 or >1.5. RESULTS: A total of 211 (44%) individuals had PiB >1.4 and 151
      (31%) >1.5. In univariate and multivariate models, discrimination was modest
      (AUROC ~0.6-0.7). Multivariately, age and APOE best predicted odds of PiB >1.4
      and >1.5. Subjective memory complaints were similar to cognitive test performance
      in predicting PiB >1.5. Indicators of PiB positivity varied with age. Screening
      APOE epsilon4 carriers alone reduced the number needed to screen to enroll 100
      subjects with PIB >1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89.
      CONCLUSIONS: Age and APOE genotype are useful predictors of the likelihood of
      significant amyloid accumulation, but discrimination is modest. Nonetheless,
      these results suggest that inexpensive and noninvasive measures could
      significantly reduce the number of CN individuals needed to screen to enroll a
      given number of amyloid-positive subjects.

PMID- 22972645
TI  - Population-based study of capsular warning syndrome and prognosis after early
      recurrent TIA.
AB  - OBJECTIVE: Many guidelines recommend emergency assessment for patients with >=2
      TIAs within 7 days, perhaps in recognition of the capsular warning syndrome.
      However, it is unclear whether all patients with multiple TIAs are at high early
      risk of stroke and whether treatable underlying pathologies are more prevalent in
      this group. METHODS: We studied clinical characteristics, Trial of Org 10172 in
      Acute Stroke Treatment (TOAST) classification, and risk of stroke in 1,000
      consecutive patients with incident and recurrent TIAs in a prospective,
      population-based study (Oxford Vascular Study). RESULTS: Of 1,000 patients with
      TIAs, 170 had a further TIA within 7 days (105 within 24 hours). Multiple TIAs
      were not associated with carotid stenosis or atrial fibrillation, and much of the
      10.6 (95% confidence interval [CI] 6.5-15.9) risk of stroke during the 7 days
      after the first TIA was due to patients with small-vessel disease (SVD) etiology
      (10 of 24 vs 8 of 146, odds ratio [OR] = 12.3, 95% CI 3.7-41.9, p < 0.0001),
      particularly those with motor weakness (i.e., capsular warning syndrome) compared
      with hemisensory events (9 of 15 [60%], 95% CI 35.3-84.7 vs 1 of 9 [11.1%], 95%
      CI 0-31.7, p = 0.03). The 7-day risk of stroke after a recurrent TIA was similar
      to the risk after a single TIA in patients with non-SVD TIA (8 of 146 [5.5%] vs
      76 of 830 [9.2%], OR = 0.58, 95% CI 0.25-1.3, p = 0.20). Of the 9 patients with
      stroke after a capsular warning syndrome, all had the recurrent TIA within 24
      hours after the first TIA, and the subsequent stroke occurred within 72 hours of
      the second TIA in 8. The ABCD2 scores of all preceding TIAs were >=4 in all 9
      patients with capsular warning syndrome before stroke. CONCLUSIONS: Capsular
      warning syndrome is rare (1.5% of TIA presentations) but has a poor prognosis (7
      day stroke risk of 60%). Otherwise, recurrent TIA within 7 days is not associated
      with a greater stroke risk than that after a single TIA.

PMID- 22972647
TI  - Brain MRI markers and dropout in a longitudinal study of cognitive aging: the
      Three-City Dijon Study.
AB  - OBJECTIVE: Longitudinal studies of dementia rely on the assumption that
      individuals who drop out are comparable to those who remain in the study,
      adjusting for measured covariates. Existing methods to handle dropouts account
      for differences based on past health and cognitive measures. We assess whether
      such adjustments fully account for differences in future dementia risk. METHODS:
      Among Three-City Study participants in Dijon, France, with 1 (n = 1,633) or 2 (n
      = 1,168) brain MRI scans, we tested whether white matter lesion volume (WMLV),
      hippocampal volume, or brain CSF volume predicted dropout ("unable to contact" or
      "refused interview") in repeated-measures logistic regression with up to 4 follow
      ups (average 3.5 waves). Using linear regression, we also estimated differences
      in MRI volumes and MRI changes by subsequent dropout status and estimated
      plausible ranges for selective attrition bias based on these associations. Models
      were adjusted for demographic, health, and cognitive score covariates. RESULTS:
      Baseline greater WMLV predicted increased odds of dropping out (adjusted odds
      ratio = 1.71; 95% confidence interval [CI] 1.20-2.43). Among participants with 2
      MRI scans, individuals who subsequently dropped out had significantly worse
      declines in hippocampal volume (-0.30 SD difference; 95% CI -0.43 to -0.17)
      between the first and second MRI scans. CONCLUSIONS: Higher future dementia risk,
      indicated by worse past brain MRI findings, predicted future study dropout.
      Adjustment for selective attrition, based on MRI markers when available, may help
      reduce bias in estimates of dementia incidence and improve research on dementia
      risk factors. MRI findings may also help prospectively identify cohort members at
      elevated risk of attrition.

PMID- 22972648
TI  - Adjunctive dexamethasone in adults with meningococcal meningitis.
AB  - OBJECTIVES: We evaluated the implementation and effectiveness of adjunctive
      dexamethasone in adults with meningococcal meningitis. METHODS: We compared 2
      Dutch prospective nationwide cohort studies on community-acquired meningococcal
      meningitis. A total of 258 patients with CSF culture-proven meningitis were
      enrolled between 1998 and 2002, before routine dexamethasone therapy was
      introduced, and 100 patients from March 2006 to January 2011, after guidelines
      recommended dexamethasone. RESULTS: Dexamethasone was administered in 43 of 258
      (17%) patients in the 1998-2002 cohort and in 86 of 96 (90%) patients in the 2006
      2011 cohort (p < 0.001), and was started with or before the first dose of
      antibiotics in 12 of 258 (5%) and 85 of 96 (89%) patients (p < 0.001). Rates of
      unfavorable outcome were similar between cohorts (12 of 100 [12%] vs 30 of 258
      [12%]; p = 0.67), also after correction for meningococcal serogroup. The rates of
      hearing loss (3 of 96 [3%] vs 19 of 237 [8%]; p = 0.10) and death (4 of 100 [4%]
      vs 19 of 258 [7%]; p = 0.24) were lower in the 2006-2011 cohort, but this did not
      reach significance. The rate of arthritis was lower in patients treated with
      dexamethasone (32 of 258 [12%] vs 5 of 96 [5%], p = 0.046). Dexamethasone was not
      associated with adverse events. CONCLUSIONS: Adjunctive dexamethasone is widely
      prescribed for patients with meningococcal meningitis and is not associated with
      harm. The rate of arthritis has decreased after the implementation of
      dexamethasone. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence
      that adjuvant dexamethasone in adults with meningococcal meningitis does not
      increase negative outcomes such as deafness, death, or negative Glasgow Outcome
      Scale measures.

PMID- 22972649
TI  - Functional plasticity in MS: friend or foe?

PMID- 22972650
TI  - The ALS-FTD-Q: a new screening tool for behavioral disturbances in ALS.
AB  - OBJECTIVE: The assessment of behavioral disturbances in amyotrophic lateral
      sclerosis (ALS) is important because of the overlap with the behavioral variant
      of frontotemporal dementia (ALS-bvFTD). Motor symptoms and dysarthria are not
      taken into account in currently used behavioral questionnaires. We examined the
      clinimetric properties of a new behavioral questionnaire for patients with ALS
      (Amyotrophic Lateral Sclerosis-Frontotemporal Dementia-Questionnaire [ALS-FTD
      Q]). METHODS: In addition to other clinimetric properties, we examined
      reliability, clinical validity, and construct validity of the ALS-FTD-Q, using
      data from patients with ALS (n = 103), ALS-bvFTD (n = 10), bvFTD (n = 25), muscle
      disease control subjects (n = 39), and control subjects (n = 31). Construct
      validity of the ALS-FTD-Q was assessed using the Frontal Systems Behavior scale
      (FrSBe), Frontal Behavioral Inventory (FBI), Hospital Anxiety and Depression
      Scale, ALS Functional Rating Scale-Revised, Frontal Assessment Battery, Mini
      Mental State Examination, and a fluency index. In addition, the point prevalence
      of behavioral disturbances according to the ALS-FTD-Q was compared with those
      obtained with the FrSBe and FBI. RESULTS: The internal consistency of the ALS-FTD
      Q was good (Cronbach alpha = 0.92). The ALS-FTD-Q showed construct validity
      because it correlated highly with other behavioral measures (r = 0.80 and 0.79),
      moderately with measures of frontal functions and global cognitive functioning (r
      = 0.37; r = 0.32), and poorly with anxiety/depression and motor impairment (r =
      0.18 for both). The ALS-FTD-Q discriminated between patients with ALS-bvFTD,
      patients with ALS, and control subjects. The point prevalence of behavioral
      disturbances in patients with ALS measured with the ALS-FTD-Q was lower than that
      for the FrSBe and FBI. CONCLUSION: The ALS-FTD-Q is a feasible and
      clinimetrically validated instrument for the screening of behavioral disturbances
      in ALS.

PMID- 22972651
TI  - Heterogeneity of cortical lesions in multiple sclerosis: clinical and pathologic
      implications.
AB  - OBJECTIVE: Autopsy cases show that cortical lesions (CLs) in multiple sclerosis
      (MS) lack lymphocyte/macrophage influx, blood-brain barrier breakdown, and
      complement activation. However, some CLs were demonstrated to harbor activated
      microglia. Here, we assessed the clinical significance of microglia activation in
      CLs in a large autopsy sample, and we investigated possible interrelationships
      with other pathologic characteristics. METHODS: We cross-sectionally investigated
      the clinicopathologic characteristics of 22 patients with MS with extensive
      subpial demyelination (CL group) and 19 patients with MS with only little
      demyelination of the cerebral cortex (non-CL group). RESULTS: A subset of the
      patients in the CL group (12 patients) showed rims of activated microglia (RAM)
      at the border of the CLs (RAM-CL group), whereas the other 10 patients in this
      group did not show microglia activation (non-RAM-CL group). A subsequent
      comparison between groups showed that patients with MS harboring RAM-CLs were
      significantly younger at the time of their death (53.5 years) than patients
      harboring mainly non-RAM-CLs (68.7 years; p < 0.05) or patients without extensive
      numbers of CLs (66.9 years; p < 0.01). In addition, a significantly shorter
      disease duration was found for the RAM-CL group (mean 20.9 years) than for the
      non-CL group (mean 34.5 years; p < 0.05). We also found that the presence of RAM
      CLs is associated with a higher number of chronic active white matter (WM)
      lesions (Spearman rho = 0.74; p < 0.0001). CONCLUSIONS: RAM-CLs were found in a
      subset of patients with MS who also have more active WM inflammation and a less
      favorable disease course.

PMID- 22972646
TI  - Vascular burden and Alzheimer disease pathologic progression.
AB  - OBJECTIVE: To investigate the vascular contribution to longitudinal changes in
      Alzheimer disease (AD) biomarkers. METHODS: The Alzheimer's Disease Neuroimaging
      Initiative is a clinic based, longitudinal study with CSF, PET, and MRI
      biomarkers repeatedly measured in participants with normal cognition (NC), mild
      cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular
      risks were excluded. Cardiovascular risk scores and MRI white matter
      hyperintensities (WMHs) were treated as surrogate markers for vascular burden.
      Generalized estimating equations were applied, and both vascular burden and its
      interaction with time (vascular burden * time) or time-varying WMHs were entered
      into regression models to assess whether biomarker rates of change were modified
      by vascular burden. RESULTS: Cardiovascular risk profiles were not predictive of
      progression in CSF beta42-amyloid, [18F]fluorodeoxyglucose (FDG) PET uptake, and
      MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were
      generally associated with cognitive impairment, particularly poor executive
      function. WMHs increased over time with a faster rate in MCI and AD than in NC.
      Increased time-varying WMH was associated with faster decline in executive
      function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF
      and MRI biomarkers in the 3 groups. These findings remained unchanged after
      accounting for APOE4. CONCLUSION: Increased WMHs are associated with aging,
      decreased glucose metabolism, and decline in executive function but do not affect
      AD-specific pathologic progression, suggesting that the vascular contribution to
      dementia is probably additive although not necessarily independent of the amyloid
      pathway.

PMID- 22972652
TI  - Total knee arthroplasty with a computer-navigated saw: a pilot study.
AB  - BACKGROUND: Computer-aided surgery aims to improve implant alignment in TKA but
      has only been adopted by a minority for routine use. A novel approach, navigated
      freehand bone cutting (NFC), is intended to achieve wider acceptance by
      eliminating the need for cumbersome, implant-specific mechanical jigs and
      avoiding the expense of navigation. QUESTIONS/PURPOSES: We determined cutting
      time, surface quality, implant fit, and implant alignment after NFC of synthetic
      femoral specimens and the feasibility and alignment of a complete TKA performed
      with NFC technology in cadaveric specimens. METHODS: Seven surgeons prepared six
      synthetic femoral specimens each, using our custom NFC system. Cutting times,
      quality of bone cuts, and implant fit and alignment were assessed quantitatively
      by CT surface scanning and computational measurements. Additionally, a single
      surgeon performed a complete TKA on two cadaveric specimens using the NFC system,
      with cutting time and implant alignment analyzed through plain radiographs and
      CT. RESULTS: For the synthetic specimens, femoral coronal alignment was within +/
      2 degrees  of neutral in 94% of the specimens. Sagittal alignment was within 0
      degrees  to 5 degrees  of flexion in all specimens. Rotation was within +/- 1
      degrees  of the epicondylar axis in 97% of the specimens. The mean time to make
      cuts improved from 13 minutes for the first specimen to 9 minutes for the fourth
      specimen. TKA was performed in two cadaveric specimens without complications and
      implants were well aligned. CONCLUSIONS: TKA is feasible with NFC, which
      eliminates the need for implant-specific instruments. We observed a fast learning
      curve. CLINICAL RELEVANCE: NFC has the potential to improve TKA alignment, reduce
      operative time, and reduce the number of instruments in surgery. Fewer
      instruments and less sterilization could reduce costs associated with TKA.

PMID- 22972653
TI  - Can fresh osteochondral allografts restore function in juveniles with
      osteochondritis dissecans of the knee?
AB  - BACKGROUND: Failure of initial treatment for juvenile osteochondritis dissecans
      (OCD) may require further surgical intervention, including microfracture,
      autograft chondrocyte implantation, osteochondral autografting, and fresh
      osteochondral allografting. Although allografts and autografts will restore
      function in most adults, it is unclear whether fresh osteochondral allograft
      transplantations similarly restore function in skeletally immature patients who
      failed conventional treatment. QUESTIONS/PURPOSES: Therefore, we determined
      function in (1) daily activity; (2) sports participation; and (3) healing (by
      imaging) in children with juvenile OCD who failed conventional therapy and
      underwent fresh osteochondral allograft transplantation. METHODS: We
      retrospectively reviewed 11 children with OCD of the knee treated with a fresh
      stored osteochondral allograft between 2004 and 2009 (six males and five
      females). The average age of the children at the time of their allograft surgery
      was 15.2 years (range, 13-20 years). The clinical assessments included physical
      examination, radiography, MRI, and a modified Merle D'Aubigne-Postel score. The
      size of the allograft was an average of 5.11 cm(2). The minimum followup was 12
      months (average, 24 months; range, 12-41 months). RESULTS: All patients had
      returned to activities of daily living without difficulties at 6 months and
      returned to full sports activities between 9 and 12 months after surgery. The
      modified Merle D'Aubigne-Postel score improved from an average of 12.7
      preoperatively to 16.3 at 24 months postoperatively. Followup radiographs at 2
      years showed full graft incorporation and no demarcation between the host and
      graft bone. CONCLUSIONS: Our observations suggested fresh osteochondral
      allografts restored short-term function in patients with juvenile OCD who failed
      standard treatments. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22972654
TI  - A novel imaging system permits real-time in vivo tumor bed assessment after
      resection of naturally occurring sarcomas in dogs.
AB  - BACKGROUND: Treatment of soft tissue sarcoma (STS) includes complete tumor
      excision. However, in some patients, residual sarcoma cells remain in the tumor
      bed. We previously described a novel hand-held imaging device prototype that uses
      molecular imaging to detect microscopic residual cancer in mice during surgery.
      QUESTIONS/PURPOSES: To test this device in a clinical trial of dogs with
      naturally occurring sarcomas, we asked: (1) Are any adverse clinical or
      laboratory effects observed after intravenous administration of the fluorescent
      probes? (2) Do canine sarcomas exhibit fluorescence after administration of the
      cathepsin-activated probe? (3) Is the tumor-to-background ratio sufficient to
      distinguish tumor from tumor bed? And (4) can residual fluorescence be detected
      in the tumor bed during surgery and does this correlate with a positive margin?
      METHODS: We studied nine dogs undergoing treatment for 10 STS or mast cell
      tumors. Dogs received an intravenous injection of VM249, a fluorescent probe that
      becomes optically active in the presence of cathepsin proteases. After injection,
      tumors were removed by wide resection. The tumor bed was imaged using the novel
      imaging device to search for residual fluorescence. We determined correlations
      between tissue fluorescence and histopathology, cathepsin protease expression,
      and development of recurrent disease. Minimum followup was 9 months (mean, 12
      months; range, 9-15 months). RESULTS: Fluorescence was apparent from all 10
      tumors and ranged from 3 * 10(7) to 1 * 10(9) counts/millisecond/cm(2). During
      intraoperative imaging, normal skeletal muscle showed no residual fluorescence.
      Histopathologic assessment of surgical margins correlated with intraoperative
      imaging in nine of 10 cases; in the other case, there was no residual
      fluorescence, but tumor was found at the margin on histologic examination. No
      animals had recurrent disease at 9 to 15 months. CONCLUSIONS: These initial
      findings suggest this imaging system might be useful to intraoperatively detect
      residual tumor after wide resections. CLINICAL RELEVANCE: The ability to assess
      the tumor bed intraoperatively for residual disease has the potential to improve
      local control.

PMID- 22972655
TI  - Making a case for the socioeconomic determinacy of survival in osteosarcoma.
AB  - BACKGROUND: The literature on osteosarcoma survival generally focuses on tumor
      and treatment variables, although it is unclear whether and how ethnic and
      socioeconomic factors might influence survival. QUESTIONS/PURPOSES: We therefore
      investigated the relative contribution of socioeconomic influences together with
      more traditional tumor-specific factors on osteosarcoma survival. METHODS: We
      performed survival analyses on two national databases in two countries. Using
      multivariable analyses, we compared these with corresponding institution-specific
      survival to determine if socioeconomic factors might impact osteosarcoma
      survival. RESULTS: East Asian descent, state-specific treatment, female sex,
      treatment in the 1990s, low-grade disease, intracompartmental disease, small
      size, wide resections as opposed to forequarter or hindquarter amputations, and
      single primaries were good prognostic factors. Survival was better in the more
      affluent states. Males were affected at an older age than females. Blacks tended
      to have larger tumors, although their overall survival was similar to whites.
      East Asians were more likely to be treated in the 1990s with wide resections for
      smaller tumors and were located around states associated with good treatment.
      East Asians in Singapore and the United States had the same survival. Survival in
      East Asians in Singapore was similar to that of other races. The provision of
      health care for osteosarcoma varies greatly across the United States but is
      uniform in the socialized medical system in Singapore. Hence, the observed
      differences in the United States were likely the result of socioeconomic factors.
      CONCLUSIONS: Our analysis suggests ethnic and economic bias may influence
      survival in osteosarcoma and should receive greater attention in the collective
      literature on survival analyses. LEVEL OF EVIDENCE: Level II, prognostic study.
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 22972657
TI  - Surgical resection of relapse may improve postrelapse survival of patients with
      localized osteosarcoma.
AB  - BACKGROUND: Despite neoadjuvant chemotherapy and wide surgical ablation, 15% to
      25% of patients with primary osteosarcoma will relapse (local recurrence or
      metastases). Neither chemotherapy nor radiation therapy alone will render a
      patient disease-free without concomitant surgical ablation of relapse. We prefer
      excision of relapse when possible. However, it is unclear whether excision
      enhances survival. QUESTIONS/PURPOSES: We therefore determined (1) onset,
      location, and treatments for relapse; (2) postrelapse disease-free survival of
      patients who underwent surgical ablation and those who did not; and (3) relapse
      free interval between initial diagnosis and first relapse in survivors and in
      those who died of their disease. METHODS: We retrospectively reviewed 15 children
      who initially presented with localized, nonmetastatic extremity osteosarcoma and
      attained initial complete remission after neoadjuvant chemotherapy, wide local
      resection, postoperative chemotherapy, and subsequently developed disease
      relapse. Relapse occurred at a median of 28 months, although late relapse after 5
      years occurred in three. We resected the recurrent tumor in nine patients and
      treated six nonoperatively. RESULTS: Seven of nine surgically treated patients
      had a postrelapse disease-free survival ranging from 3 to 14 years and an overall
      survival ranging from 7 to 16 years. Patients not surgically treated all died
      within 40 months of their relapse. The median relapse-free interval in patients
      who survived was longer 34 months (range, 17-152 months) as compared with 17
      months (range, 7-40 months) in those who died of their disease. CONCLUSIONS: Our
      data confirm the importance of surgery in patients with relapsed osteosarcoma.
      Disease-free survival in patients with relapsed osteosarcoma is only possible if
      complete remission is attained. Patients with late relapse may have a better
      chance of survival. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 22972656
TI  - All-polyethylene tibial components are equal to metal-backed components:
      systematic review and meta-regression.
AB  - BACKGROUND: Less than 1% of all primary TKAs are performed with an all
      polyethylene tibial component, although recent studies indicate all-polyethylene
      tibial components are equal to or better than metal-backed ones.
      QUESTIONS/PURPOSES: We asked whether the metal-backed tibial component was
      clinically superior to the all-polyethylene tibial component in primary TKAs
      regarding revision rates and clinical functioning, and which modifying variables
      affected the revision rate. METHODS: We systematically reviewed the literature
      for clinical studies comparing all-polyethylene and metal-backed tibial
      components used in primary TKAs in terms of revision rates, clinical scores, and
      radiologic parameters including radiostereometric analysis (RSA). Meta-regression
      techniques were used to explore factors modifying the observed effect. Our search
      yielded 1557 unique references of which 26 articles were included, comprising
      more than 12,500 TKAs with 231 revisions for any reason. RESULTS: Meta-analysis
      showed no differences between the all-polyethylene and metal-backed components
      except for higher migration of the metal-backed components. Meta-regression
      showed strong evidence that the all-polyethylene design has improved with time
      compared with the metal-backed design. CONCLUSIONS: The all-polyethylene
      components were equivalent to metal-backed components regarding revision rates
      and clinical scores. The all-polyethylene components had better fixation (RSA)
      than the metal-backed components. The belief that metal-backed components are
      better than all-polyethylene ones seems to be based on studies from earlier TKAs.
      This might no longer be true for modern TKAs. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 22972658
TI  - Surgery quality and tumor status impact on survival and local control of
      resectable liposarcomas of extremities or the trunk wall.
AB  - BACKGROUND: The 5-year survival rates for localized liposarcomas reportedly vary
      from 75% to 91% with histologic grade as the most important prognostic factor.
      However, it is unclear which other factors, including the initial surgery quality
      and recurrent tumors, influence survival in localized liposarcomas (LPS).
      QUESTIONS/PURPOSES: We analyzed factors (including AJCC staging system)
      influencing survival and local control of resectable LPS of the extremities/trunk
      wall and the impact of surgery quality and tumor status and type of disease
      recurrences according to pathological subtype. METHODS: We retrospectively
      reviewed 181 patients with localized LPS: 110 were treated for primary tumors, 50
      for recurrent tumors, and 21 for wide scar resection after unplanned nonradical
      resection. We determined survival rates and examined factors influencing
      survival. The minimum followup was 4 months (median, 52 months; range, 4-168
      months). RESULTS: Five-year disease-specific (DSS), disease-free (DFS), and local
      relapse-free survival (LRFS) rates were: 80%, 58%, and 75%, respectively. Five
      year local relapse-free survival rates for primary versus clinically recurrent
      tumor versus scar after nonradical resection were: 86.1%, 52.1%, and 73.3%,
      respectively. The following were independent negative prognostic factors for DSS
      (AJCC Stage >= IIb), DFS (Grade 3; clinical recurrence; skin infiltration), and
      LRFS (clinical recurrence; R1 resection). An unplanned excision, although
      influencing local relapse-free survival, had no impact on disease-specific
      survival (calculated from date of first excision 5-year rate of 80%, considering
      impact of combined treatment of clinical recurrence/scar). CONCLUSIONS: We
      confirmed the value of AJCC staging for predicting disease-specific survival in
      extremity/trunk wall LPS. Radical reresection of scar after nonradical primary
      tumor resection (+ radiotherapy) seems to improve disease-free and local relapse
      free survival in liposarcomas. Patients with unplanned excision can be cured when
      referred to a sarcoma unit. LEVEL OF EVIDENCE: Level IV, prognostic study. See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 22972659
TI  - Surgical technique: repair of forefoot skin and soft tissue defects using a
      lateral tarsal flap with a reverse dorsalis pedis artery pedicle: a retrospective
      study of 11 patients.
AB  - BACKGROUND: Various authors have proposed flaps to reconstruct traumatic forefoot
      skin and soft tissue defects, especially with exposure of tendon and/or bone
      although which is best for particular circumstances is unclear. DESCRIPTION OF
      TECHNIQUE: The indications for the technique were a forefoot defect area of no
      more than 8-cm * 8-cm and a well-preserved lateral tarsal (LT) donor site. The
      injured tendons were repaired using tendon grafts. The free dorsalis pedis flap
      was outlined by centering it on the cutaneous branch of the LT artery and
      tailoring it to the size of the wound, allowing 0.5-cm margins in length and
      width. The flap was rotated around the plantar perforating branch of the dorsalis
      pedis artery (DPA) to cover the forefoot defect. The lateral dorsalis pedis
      cutaneous nerve was anastomosed with the recipient plantar nerve stump. The donor
      site was covered with an inguinal, full-thickness skin graft. PATIENTS AND
      METHODS: Traumatic forefoot skin and soft tissue defects with exposure of the
      tendon and/or bone involving 11 feet in 11 patients (mean age, 32 years) were
      covered using a LT flap with a reversed DPA pedicle. Three patients with forefoot
      defects underwent emergency repair within 8 hours of injury, whereas eight
      patients required delayed repair. All patients were followed up for at least 6
      months (mean, 13 months; range, 6-24 months). RESULTS: All flaps survived
      uneventfully, except for two that had superficial marginal necrosis or severe
      venous insufficiency. All skin grafts covering the donor sites survived and all
      wounds healed. None of the patients had restricted standing or walking at
      followups. The two-point discrimination was 4 mm to 10 mm at 6 months
      postoperative. The mean hallux-metatarsophalangeal-interphalangeal scale score
      was 93 points (range, 87-98 points). CONCLUSIONS: Our observations suggest the LT
      flap with a reversed DPA pedicle is a reasonable option for repair of traumatic
      forefoot skin and soft tissue defects with exposure of tendon and/or bone but a
      well-preserved LT donor site and is associated with minimal morbidity.

PMID- 22972661
TI  - The regulation of endogenous retinoic acid level through CYP26B1 is required for
      elevation of palatal shelves.
AB  - BACKGROUND: In previous studies, we investigated the effects of excess retinoic
      acid (RA) during palatogenesis by RA administration to pregnant mice. In the
      present study, we deleted Cyp26b1, one of the RA-degrading enzymes, to further
      study the effects of excess RA in the normal developing palate and to understand
      how endogenous levels of RA are regulated. RESULTS: Excess RA, due to the absence
      of Cyp26b1, targets cells in the bend region of the palatal shelves and inhibits
      their horizontal elevation, leading to cleft palate. An organ culture of Cyp26b1
      /- palatal shelves after tongue removal did not rescue the impaired elevation of
      the palatal shelves. The expression of Fgf10, Bmp2, and Tbx1, important molecules
      in palatal development, was down-regulated. Cell proliferation was decreased in
      the bend region of palatal shelves. Tongue muscles were hypoplastic and/or
      missing in Cyp26b1-/- mice. CONCLUSIONS: We demonstrated that CYP26B1 is
      essential during palatogenesis. Excess RA due to the lack of Cyp26b1 suppresses
      the expression of key regulators of palate development in the bend region,
      resulting in a failure in the horizontal elevation of the palatal shelves. The
      regulation of RA signaling through CYP26B1 is also necessary for the development
      of tongue musculature and for tongue depression.

PMID- 22972663
TI  - Coronary artery fistula with a giant aneurysm treated by percutaneous transradial
      embolization.
AB  - Coronary artery fistulas are rare anomalies that are very rarely accompanied by
      an aneurysm. The minimally invasive method of percutaneous transradial
      embolization, using a thin guiding catheter, was used to treat a coronary artery
      fistula with an associated giant aneurysm. This technique, not previously
      described for this type of application, is presented as a case report. The
      successful outcome of this procedure demonstrated that transradial coronary
      interventions are useful for treating coronary artery fistulas with an associated
      giant aneurysm, especially in patients at high risk for conventional surgery or
      transfemoral interventions.

PMID- 22972662
TI  - An information criterion for marginal structural models.
AB  - Marginal structural models were developed as a semiparametric alternative to the
      G-computation formula to estimate causal effects of exposures. In practice, these
      models are often specified using parametric regression models. As such, the usual
      conventions regarding regression model specification apply. This paper outlines
      strategies for marginal structural model specification and considerations for the
      functional form of the exposure metric in the final structural model. We propose
      a quasi-likelihood information criterion adapted from use in generalized
      estimating equations. We evaluate the properties of our proposed information
      criterion using a limited simulation study. We illustrate our approach using two
      empirical examples. In the first example, we use data from a randomized
      breastfeeding promotion trial to estimate the effect of breastfeeding duration on
      infant weight at 1 year. In the second example, we use data from two prospective
      cohorts studies to estimate the effect of highly active antiretroviral therapy on
      CD4 count in an observational cohort of HIV-infected men and women. The marginal
      structural model specified should reflect the scientific question being addressed
      but can also assist in exploration of other plausible and closely related
      questions. In marginal structural models, as in any regression setting, correct
      inference depends on correct model specification. Our proposed information
      criterion provides a formal method for comparing model fit for different
      specifications.

PMID- 22972664
TI  - Spinoza's error: memory for truth and falsity.
AB  - Two theoretical frameworks have been proposed to account for the representation
      of truth and falsity in human memory: the Cartesian model and the Spinozan model.
      Both models presume that during information processing a mental representation of
      the information is stored along with a tag indicating its truth value. However,
      the two models disagree on the nature of these tags. According to the Cartesian
      model, true information receives a "true" tag and false information receives a
      "false" tag. In contrast, the Spinozan model claims that only false information
      receives a "false" tag, whereas untagged information is automatically accepted as
      true. To test the Cartesian and Spinozan models, we conducted two source memory
      experiments in which participants studied true and false trivia statements from
      three different sources differing in credibility (i.e., presenting 100% true, 50%
      true and 50% false, or 100% false statements). In Experiment 1, half of the
      participants were informed about the source credibility prior to the study phase.
      As compared to a control group, this precue group showed improved source memory
      for both true and false statements, but not for statements with an uncertain
      validity status. Moreover, memory did not differ for truth and falsity in the
      precue group. As Experiment 2 revealed, this finding is replicated even when
      using a 1-week rather than a 20-min retention interval between study and test
      phases. The results of both experiments clearly contradict the Spinozan model but
      can be explained in terms of the Cartesian model.

PMID- 22972665
TI  - Idealness and similarity in goal-derived categories: a computational examination.
AB  - The finding that the typicality gradient in goal-derived categories is mainly
      driven by ideals rather than by exemplar similarity has stood uncontested for
      nearly three decades. Due to the rather rigid earlier implementations of
      similarity, a key question has remained--that is, whether a more flexible
      approach to similarity would alter the conclusions. In the present study, we
      evaluated whether a similarity-based approach that allows for dimensional
      weighting could account for findings in goal-derived categories. To this end, we
      compared a computational model of exemplar similarity (the generalized context
      model; Nosofsky, Journal of Experimental Psychology. General 115:39-57, 1986) and
      a computational model of ideal representation (the ideal-dimension model;
      Voorspoels, Vanpaemel, & Storms, Psychonomic Bulletin & Review 18:1006-114, 2011)
      in their accounts of exemplar typicality in ten goal-derived categories. In terms
      of both goodness-of-fit and generalizability, we found strong evidence for an
      ideal approach in nearly all categories. We conclude that focusing on a limited
      set of features is necessary but not sufficient to account for the observed
      typicality gradient. A second aspect of ideal representations--that is, that
      extreme rather than common, central-tendency values drive typicality--seems to be
      crucial.

PMID- 22972668
TI  - Treatment of adriamycin-induced nephropathy with erythropoietin and G-CSF.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and Erythropoietin
      (EPO) are known to stimulate the growth and differentiation of progenitor cells
      to prevent acute renal injury. This study aimed to assess the use of growth
      factors to mobilize stem cell in a mouse model of adriamycin-induced chronic
      kidney disease. METHODS: All animals were injected with adriamycin for kidney
      injury and allocated into three treatment groups (G-CSF, EPO and G-CSF + EPO),
      and a control group (adriamycin alone). RESULTS: Number of atrophic sites,
      glomerulosclerosis rate and interstitial fibrosis severity score were assessed in
      all groups. In all treatment groups, histologic parameters did not significantly
      differ, but were lower than in the control group (P<.001). Scal and CD34
      expressions among treatment groups showed no statistically significant
      difference, but were higher than in the control group (P<.0001). CD105 expression
      was higher in EPO and G+EPO as compared to G-CSF and the control group (P<.0001),
      with no statistically significant difference between the latter two groups (P =
      NS). CONCLUSION: G-CSF and EPO had a histologic protective effect, while
      treatment with EPO + G-CSF had no additive effects in a model of adriamycin
      induced chronic kidney disease.

PMID- 22972669
TI  - Comprehensive geriatric assessment in the hemodialysis elderly population.
AB  - The aim of this study was to assess the usefulness of a Multidimensional
      Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) in
      defining comorbidity and the need for a multidisciplinary approach in older
      patients with end-stage renal disease. This was a cross-sectional study that
      included 162 patients, 103 aged 65 and over with a diagnosis of end-stage renal
      disease and ongoing chronic hemodialysis treatment. Results were compared with a
      group of 250 geriatric patients without renal impairment. A standardized CGA that
      included information on clinical, cognitive, functional and nutritional aspects,
      as well as comorbidity, medications and social support network, was used to
      calculate MPI. Among the dialysis patients, the vast majority showed a moderate
      (58.3%) or high risk score (19.4%). MPI score was clearly correlated with
      Charlson index (P = .001) both in the global population and the dialysis patients
      aged over 65. Compared to geriatric patients without renal failure, all MPI score
      domains were more compromised in the dialysis population. These preliminary
      findings strongly suggest that MPI may be very useful to assess the clinical
      picture of older patients undergoing renal replacement therapy (RRT). Its use in
      the dialysis population under 65 needs to be investigated.

PMID- 22972670
TI  - Microarray applications in nephrology with special focus on transplantation.
AB  - The increase in progressive kidney disease, rising numbers of patients with end
      stage renal disease, organ shortages for kidney transplants and poor long-term
      graft survival rates underline the need for better strategies to diagnose,
      prevent and treat renal disease. Histological analysis, based on renal biopsies
      and readings of morphology, has limitations as key information for the management
      of the individual patient, and complementary technologies are needed. The
      sequencing of the human genome has provided the platform for applied molecular
      phenotyping. Microarray technology has become a routine method for robust high
      throughput measurements of genome-wide transcriptome levels. This review will
      give examples of transcriptome profiling in nephrology and focus on lessons
      learned from studies in kidney transplantation. Molecular profiling detects
      changes not seen by morphology or captured by clinical markers. Gene expression
      signatures provide quantitative measurements of inflammatory burden and immune
      activation or metabolism, and reflect coordinated changes in pathways associated
      with injury and repair. Transcriptome profiling has the potential to improve our
      understanding of disease mechanisms, may provide tools to reclassify disease
      entities and be potentially helpful in individualizing therapies and predicting
      outcomes. However, description of transcriptome patterns is not an end in itself.
      The identification of predictive gene sets and the application to an
      individualized patient management requires integration of clinical and pathology
      based variables as well as more objective reference markers and hard end points.

PMID- 22972667
TI  - Awareness of kidney diseases in general population and in high school students.
      Italian report for World Kidney Days 2010-2011.

PMID- 22972671
TI  - Renal transplant allocation criteria, desensitization strategies and
      immunosuppressive therapy in retransplant renal patients.
AB  - This review covers the issue of kidney retransplantation. Patients waiting for a
      second transplant are increasing in number, and it is more and more difficult to
      find a suitable kidney. The main reasons are both clinical and immunological.
      Immunological problems are the most difficult to overcome. New techniques allow
      the identification of anti-HLA antibodies previously not easy to find. As a
      consequence, patients waiting for a new transplant are often hyperimmunized, and
      the cross-match is often positive. The authors discuss several immunosuppressive
      approaches for such patients and new allocation criteria to allow an easier
      retransplant. New allocation programs such as acceptable mismatch programs and
      paired kidney exchange programs are being implemented, and new drugs are now
      emerging allowing new desensitization criteria. Some of them are not yet on the
      market, but preliminary clinical studies show such drugs to be promising in a
      short time.

PMID- 22972672
TI  - Considerations for measuring iron in post-mortem tissue of Parkinson's disease
      patients.
AB  - Redox-active iron is considered to be an important factor in the pathology and
      progression of several neurodegenerative disorders, including Parkinson's
      disease. The various roles of iron in normal physiology and its prevalence in the
      wider environment present numerous challenges to both accurate measurement and
      interpretation of brain iron levels. This review will discuss considerations for
      the analysis of iron in post-mortem samples, including how contamination, sample
      preparation and methods of analysis may influence results. In addition, several
      important factors influencing interpretation of iron levels will be considered.

PMID- 22972674
TI  - Metastasis over implantable venous access ports.
AB  - BACKGROUND: The totally implantable venous access port (TIVAP) is an important
      device for patients receiving chemotherapy. We have reported, to our knowledge,
      the first case of a metastatic tumor over a TIVAP implanted via the Seldinger
      technique with a subclavian vein puncture. METHODS: Our patient, a 48-year-old
      man with hard palate cancer, had metastasis over the TIVAP. CT studies showed
      that the tumor had spread along the catheter from the neck to the chest wall.
      RESULTS: The cause of death was multiple lung metastases and intractable tumor
      bleeding over the TIVAP. CONCLUSIONS: We present a novel case of metastasis over
      the TIVAP implanted by use of the Seldinger technique. This technique is used for
      patients receiving prolonged cytotoxic therapy for malignancy. Although the
      Seldinger technique is quick and more effective, we prefer the cephalic vein cut
      down technique when an aggressive, advanced cancer of head and neck is involved.

PMID- 22972673
TI  - Chemotherapy use and patient treatment preferences in advanced colorectal cancer:
      a prospective cohort study.
AB  - BACKGROUND: The objective of this study was to determine how patient preferences
      guide the course of palliative chemotherapy for advanced colorectal cancer.
      METHODS: Eligible patients with metastatic colorectal cancer (mCRC) were enrolled
      nationwide in a prospective, population-based cohort study. Data were obtained
      through medical record abstraction and patient surveys. Logistic regression
      analysis was used to evaluate patient characteristics associated with visiting
      medical oncology and receiving chemotherapy and patient characteristics, beliefs,
      and preferences associated with receiving >1 line of chemotherapy and receiving
      combination chemotherapy. RESULTS: Among 702 patients with mCRC, 91% consulted a
      medical oncologist; and among those, 82% received chemotherapy. Patients ages 65
      to 75 years and aged >=75 years were less likely to visit an oncologist, as were
      patients who were too sick to complete their own survey. In adjusted analyses,
      patients aged >=75 years who had moderate or severe comorbidity were less likely
      to receive chemotherapy, as were patients who were too sick to complete their own
      survey. Patients received chemotherapy even if they believed that chemotherapy
      would not extend their life (90%) or that chemotherapy would not likely help with
      cancer-related problems (89%), or patients preferred treatment focusing on
      comfort even if it meant not living as long (90%). Older patients were less
      likely to receive combination first-line therapy. Patient preferences and beliefs
      were not associated with receipt of >1 line of chemotherapy or combination
      chemotherapy. CONCLUSIONS: The majority of patients received chemotherapy even if
      they expressed negative or marginal preferences or beliefs regarding
      chemotherapy. Patient preferences and beliefs were not associated with the
      intensity or number of chemotherapy regimens.

PMID- 22972675
TI  - Effects of genetic knock-down of organic anion transporter genes on secretion of
      fluorescent organic ions by Malpighian tubules of Drosophila melanogaster.
AB  - An earlier study has shown that RNAi knock-down of a single organic anion
      transporter (OAT) gene in the principal cells of Drosophila Malpighian tubules is
      associated with reductions in the expression of multiple, functionally related
      genes. In this study, we measured the rates of secretion of four fluorescent ions
      by tubules isolated from flies expressing targeted RNAi knock-down of specific
      OAT genes. Droplets secreted by isolated tubules set up in the Ramsay assay were
      collected in optically flat capillary tubes and the concentrations of fluorescent
      ions were determined by confocal laser scanning microscopy. Reductions in the
      expression of organic anion (OA) transporting polypeptide 58Dc (OATP; CG3380)
      were associated with reduced secretion of the OAs fluorescein and Texas Red.
      Reduction in the expression of Drosophila multidrug resistance associated protein
      (dMRP; CG6214) was correlated with reduced secretion of the P-glycoprotein
      substrate daunorubicin. Secretion of the organic cation quinacrine was unaffected
      by reduced expression of OATP, dMRP, or a multidrug efflux transporter (MET;
      CG30344). The results highlight the difficulties of assigning a rate-limiting
      role in transport of a specific OA to a single membrane transporter.

PMID- 22972676
TI  - Multiphoton microscopy applications in nanodermatology.
AB  - Multiphoton microscopy is being used as a tool for tracking nanoparticles and
      assessing endogenous autofluorescent molecules. This technology is founded on
      femtosecond lasers that are capable of exciting unlabeled metal nanoparticles,
      quantum dots, and upconverting nanoparticles. The addition of time-correlated
      single-photon counting detectors enables fluorescence lifetime imaging.
      Fluorescence lifetime measurements result in high-resolution, quantitative data
      that can be used to distinguish nanoparticle signals from those of endogenous
      fluorophores. This application of multiphoton microscopy is capable of
      simultaneous nanoparticle and NAD(P)H imaging, resulting in the capacity for dye
      free assessments of treatment-induced metabolic changes. The stage is set for
      advanced, clinical imaging focused nanoparticle trials that can directly address
      critical issues in nanomedicine and nanotoxicology.

PMID- 22972677
TI  - Robustness of the hypoxic response: another job for miRNAs?
AB  - Living organisms are constantly exposed to environmental and genetic
      perturbations. Biological robustness enables these organisms to maintain their
      functional stability in the presence of external or internal changes. It has been
      proposed that microRNAs (miRNAs), small non-coding regulatory RNAs, contribute to
      robustness of gene regulatory networks. The hypoxic response is a major and well
      characterized example of a cellular and systemic response to environmental stress
      that needs to be robust. miRNAs regulate the response to hypoxia, both at the
      level of the main transcription factor that mediates this response, the hypoxia
      inducible factor (HIF), and at the level of one of the most important systemic
      outcomes of the response: angiogenesis. In this review, we will take the hypoxic
      response as a paradigm of miRNAs participating in circuits that provide
      robustness to biological responses.

PMID- 22972678
TI  - Patients without prolonged QRS after TAVI with CoreValve device do not experience
      high-degree atrio-ventricular block.
AB  - OBJECTIVE: To identify clinical and electrical factors predicting delayed high
      degree atrio-ventricular block (AVB) after transcatheter aortic valve
      implantation (TAVI). BACKGROUND: TAVI is a new technique for treating severe
      aortic valve stenosis in patients at high surgical risk but can be followed by
      high-grade AVB requiring permanent pacing (PP). METHODS AND RESULTS: The study
      included 79 patients (82 +/- 17 years, Euroscore = 23% +/- 10%) free of PP need
      before and immediately after TAVI procedure. Delayed high-degree AVB was defined
      by types 2 or 3 AVB diagnosed at least 24 hr after the index procedure. Permanent
      pacemaker implantation was performed for all these patients. We compared clinical
      and electrical variables before and after TAVI in patients with delayed AVB or
      not. TAVI was performed successfully in all patients. The 21 (26%) patients who
      exhibited delayed high-grade AVB had significantly deeper prosthesis implantation
      (12 +/- 4 mm vs. 9 +/- 5 mm, P = 0.03) and wider post-TAVI QRS duration (155 +/-
      17 msec vs. 131 +/- 25 msec, P = 0.0004), with no difference in baseline QRS
      duration. Post-TAVI QRS duration was the only independent predictor of post-TAVI
      permanent for delayed high-degree AVB (P = 0.02). After a mean follow-up of 10 +/
      8 months, all 21 patients with post-TAVI QRS <= 128 msec were free of high-grade
      AVB, whereas 21/55 (38%) patients with post-TAVI QRS >128 msec had PP (P =
      0.0016). CONCLUSION: Delayed (>24 hr after the procedure) high-grade AVB
      necessitating PP is common after TAVI. QRS duration measured immediately after
      TAVI was the best independent predictor of PP in this population. Patients with
      QRS <= 128 msec immediately after TAVI had no risk of requiring PP.

PMID- 22972679
TI  - Maximizing an ROC-type measure via linear combination of markers when the gold
      reference is continuous.
AB  - Effectively combining many classification instruments or diagnostic measurements
      together to improve the classification accuracy of individuals is a common idea
      in disease diagnosis or classification. These ensemble-type diagnostic methods
      can be constructed with respect to different kinds of performance criterions.
      Among them, the receiver operating characteristic (ROC) curve is the most popular
      criterion, which, together with some indexes derived from it, is commonly used to
      evaluate and summarize the performance of a classification instrument, such as a
      biomarker or a classifier. However, the usefulness of ROC curve and its related
      indexes relies on the existence of a binary label for each individual subject. In
      many disease diagnosis situations, such a binary variable may not exist, but only
      the continuous measurement of the true disease status is available. This true
      disease status is often referred to as the 'gold standard'. The modified area
      under ROC curve (AUC)-type measure defined by Obuchowski is a method proposed to
      accommodate such a situation. However, there is still no method for finding the
      optimal combination of diagnostic measurements, with respect to such an index, to
      have better diagnostic power than that of each individual measurement. In this
      paper, we propose an algorithm for finding the optimal combination with respect
      to such an extended AUC-type measure such that the combined measurement can have
      more diagnostic power. We illustrate the performance of our algorithm by using
      some synthesized data and a diabetes data set.

PMID- 22972680
TI  - Improved immunodetection of Taura syndrome virus using a monoclonal antibody
      specific for heterologously expressed VP1 capsid protein.
AB  - vp1, a gene encoding one of the capsid proteins of Taura syndrome virus, was
      cloned into the pGEX-6P-1 expression vector, and the resulting construct was then
      used to transform E. coli strain BL21. After induction, an N-terminally
      glutathione-S-transferase-tagged VP1 (GST-VP1) protein with a molecular mass of
      80 kDa was obtained. This protein was purified by SDS-PAGE and used for
      immunization of Swiss mice for monoclonal antibody (MAb) production. Three MAbs
      specific for the VP1 protein were selected that were suitable for detecting
      natural TSV infection in Penaeus vannamei by dot blotting, western blotting and
      immunohistochemistry. This detection occurs without cross-reaction to other
      shrimp tissues or other common shrimp viruses. As determined by dot blotting, the
      detection sensitivity of the MAbs was approximately 2 fmole/spot of the GST-VP1.
      These MAbs showed detection sensitivity comparable to that of MAbs specific for
      VP2, but they exhibited stronger immunoreactivity than previously studied MAbs
      specific for VP3. Although the sensitivity of the MAbs to VP1 was 1,000 times
      lower than one-step RT-PCR, they could be used in various types of antibody-based
      assays to confirm and enhance the detection sensitivity of TSV infection in
      shrimp.

PMID- 22972681
TI  - Discovery of a novel circular single-stranded DNA virus from porcine faeces.
AB  - A large number of novel single-stranded DNA (ssDNA) viruses have been
      characterised from various environmental sources in the last 5 years. The bulk of
      these have been from faecal sources, and faecal sampling is an ideal non-invasive
      pathogen sampling method. We characterised a novel ssDNA from a porcine faecal
      sample from Cass Basin of the South Island of New Zealand. The novel viral genome
      has two large open reading frames (ORFs), which are bidirectionally transcribed
      and separated by intergenic regions. The largest ORF has some degree of
      similarity (<30 %) to the putative capsid protein of chimpanzee stool-associated
      circular ssDNA virus (ChiSCV) and pig stool-associated single-stranded DNA virus
      (PigSCV), whereas the second-largest ORF has high similarity to the putative
      replication-associated protein (Rep) of ChiSCV (~50 %) and bovine stool
      associated circular DNA virus (BoSCV; ~30 %). Based on genome architecture,
      location of putative stem-loop like elements, and maximum-likelihood phylogenetic
      analysis of the gene encoding the Rep protein, the novel isolate belongs to the
      same family of ssDNA viruses as ChiSCV and BoSCV.

PMID- 22972682
TI  - Validity of the family-based association test for copy number variant data in the
      case of non-linear intensity-genotype relationship.

PMID- 22972684
TI  - A theoretical and experimental comparison of different techniques for B1 mapping
      at very high fields.
AB  - With the increasing use of ultrahigh-field MR with multiple transmit channels,
      mapping of the B1(+) field has become a critical factor in many studies, leading
      to the publication of a large number of sequences for the measurement of the flip
      angle in recent years. In this article, the accuracy, precision and
      practicability of some of the most prominent of these techniques are investigated
      both theoretically, using error propagation computations and Monte-Carlo
      simulations, and experimentally for different settings. For an exemplary
      experiment, which is typical for high-field applications, the flip angle
      uncertainty is calculated and measured for two- and three-dimensional
      acquisitions for techniques based on both magnitude and phase data. Simulated and
      measured results show good agreement. An experimental assessment of T1 and B0
      dependence yields weak variations with these parameters for only a few of the
      sequences. Measurements on human scanners show crucial influences of specific
      absorption rate limitations, especially at ultrahigh field.

PMID- 22972683
TI  - Nonmuscle myosin II regulation of lung epithelial morphology.
AB  - BACKGROUND: The regulation of epithelial cell shape and orientation during lung
      branching morphogenesis is not clearly understood. Nonmuscle myosins regulate
      cell size, morphology, and planar cell polarity. Here, we test the hypothesis
      that nonmuscle myosin II (NM II) regulates lung epithelial morphology in a
      spatially restricted manner. RESULTS: Epithelial cell orientation at airway tips
      in fetal mouse lungs underwent a significant transformation at embryonic day (E)
      E17. Treatment of E15 lung explants with the NM II inhibitor blebbistatin
      increased airway branching, epithelial cell size, and the degree of anisotropy in
      epithelial cells lining the airway stalks. In cultured MLE-12 lung epithelial
      cells, blebbistatin increased cell velocity, but left the migratory response to
      FGF-10 unchanged. CONCLUSIONS: In the developing lung, NM II acts to constrain
      cell morphology and orientation, but may be suppressed at sites of branching and
      cell migration. The regulation of epithelial orientation may therefore undergo
      dynamic variations from E15 to E17.

PMID- 22972686
TI  - Validity of stable isotope data in doping control: perspectives and proposals.
AB  - Delta(13)C and delta(13)C values of endogenous urinary steroids represent
      physiological random variables. Measurement uncertainty and biological scatter
      likewise contribute to the variances. The statistical distributions of negative
      controls are well investigated, but there is little knowledge about the
      corresponding distributions of steroid-users. For these reasons valid
      discrimination of steroid users from non-users by (13)C/(12)C analysis of
      endogenous steroids requires elaborate statistical treatment. Corresponding
      Bayesian approaches are presented following an introduction to the rationale. The
      use of mixture models appears appropriate. The distribution of routine data has
      been deconvolved and characterized accordingly. The mixture components, which
      presumably represent steroid users and non-users, exhibit considerable overlap.
      The validity of a given result depends on both the analytical uncertainty and the
      prior probability of doping offenses. Low analytical uncertainties but high prior
      probabilities facilitate valid detection of doping offenses. Two recommendations
      can be deduced. First, before starting an (13)C/(12)C analysis, any initial
      suspicion should be well-substantiated. This precludes use of permissive criteria
      derived from the steroid profile. Secondly, knowledge of relevant (13)C/(12)C
      distributions is required. This must cover representative numbers of authentic
      steroid users. Finally, it is desirable that the conditional probability for
      steroid administration rather than the measurement uncertainty is calculated and
      reported. This quantity possesses superior validity and it is largely independent
      of laboratory bias. The findings suggest and facilitate flexible handling of
      decision limits. Proposals for the evaluation of stable isotope data are
      presented.

PMID- 22972685
TI  - Intracoronary and retrograde coronary venous myocardial delivery of adipose
      derived stem cells in swine infarction lead to transient myocardial trapping with
      predominant pulmonary redistribution.
AB  - OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs)
      as well as their impact on coronary microcirculation following either retrograde
      coronary venous (RCV) or arterial delivery. BACKGROUND: Local delivery of ASCs to
      the heart has been proposed as a practical approach to limiting the extent of
      myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart
      have also demonstrated significant benefits from systemic (intravenous) delivery,
      prompting a question about the advantage of local delivery. There has been no
      study addressing the extent of myocardial vs. systemic disposition of ASCs in
      large animal models following local delivery to the myocardium. METHODS: In an
      initial experiment, dose-dependent effects of ASC delivery on coronary
      circulation in normal swine were evaluated to establish a tolerable ASC dosing
      range for intracoronary (IC) delivery. In a set of subsequent experiments, an
      anterior acute myocardial infarction (AMI) was created by balloon occlusion of
      the proximal left anterior descending (LAD) artery, followed by either IC or RCV
      infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI.
      Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were
      measured before sacrifices to collect tissues for analysis at 1 or 24 hr after
      cell delivery. RESULTS: IC delivery of porcine ASCs to normal myocardium was well
      tolerated up to a cumulative dose of 14 * 10(6) cells (approximately 0.5 * 10(6)
      cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at
      unit doses of 50 * 10(6) ASCs, IMR and CFR were found to be persistently altered
      in the target LAD distribution at 7 days following delivery, whereas at 10 *
      10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly
      higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV
      delivery (57.2 +/- 12.7% vs. 17.9 +/- 1.6%, P = 0.037) but this initial
      difference was not apparent at 24 hr (22.6 +/- 5.5% vs. 18.7 +/- 8.6%; P =
      0.722). In both approaches, most ASC redistributed to the pulmonary circulation
      by 24 hr postdelivery. There were no significant differences in CFR or IMR
      following ASC delivery to infarcted tissue by either route. CONCLUSIONS:
      Selective intravascular delivery of ASC by coronary arterial and venous routes
      leads to similarly limited myocardial cell retention with predominant
      redistribution of cells to the lungs. IC arterial delivery of ASC leads to only
      transiently greater myocardial retention, which is accompanied by obstruction of
      normal regions of coronary microcirculation at higher doses. The predominant
      intrapulmonary localization of cells following local delivery via both methods
      prompts the notion that systemic delivery of ASC might provide similarly
      beneficial outcomes while avoiding risks of inadvertent microcirculatory
      compromise.

PMID- 22972687
TI  - Pediatric sarcoma in Central America: outcomes, challenges, and plans for
      improvement.
AB  - BACKGROUND: Children with cancer in middle-income countries have inferior
      outcomes compared with similar children in high-income countries. The magnitude
      and drivers of this survival gap are not well understood. In the current report,
      the authors sought to describe patterns of clinical presentation, magnitude of
      treatment abandonment, and survival in children with sarcoma in Central America.
      METHODS: A retrospective review was conducted of hospital-based registries from
      national pediatric oncology referral centers. Patients with newly diagnosed
      osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma
      (STS) between January 1, 2000 and December 31, 2009 were included. Survival
      analyses were performed first using standard definitions of overall survival (OS)
      and event-free survival (EFS) and then with abandonment included as an event
      (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785
      new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175
      diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The
      rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing
      sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was
      high, particularly among patients with extremity bone sarcomas (osteosarcoma,
      30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced
      a first event, 59% had either recurrent or progressive disease. The 4-year OS
      rate (+/-standard error) was 40% +/- 3%, and the EFS rate was 30% +/- 2%;
      however, these rates decreased further to 31% +/- 2% and 24% +/- 2%,
      respectively, when abandonment was taken into account. CONCLUSIONS: The current
      results indicated that high rates of metastases and treatment abandonment and
      difficulty with upfront treatment effectiveness are important contributors to the
      poor survival of children with pediatric sarcomas in Central America. Initiatives
      for early diagnosis, psychosocial support, quality improvement, and
      multidisciplinary care are warranted to improve outcomes.

PMID- 22972688
TI  - Case of pediatric acute promyelocytic leukemia presenting as extramedullary tumor
      of the mandible.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a malignant subtype of acute
      myeloid leukemia caused by the PML-retinoic acid receptor (RAR)alpha fusion gene.
      APL may be discovered in adulthood and diagnosed after spontaneous gingival
      bleeding or difficulty in hemostasis after oral surgery such as tooth extraction.
      However, APL is extremely rare in children. METHODS AND RESULTS: A 1-year-old boy
      presented with a mass on the mentum of the mandible. The marked periosteal
      reaction was seen on CT and MRI, leading to strong suspicion of a malignant bone
      derived tumor such as a sarcoma. Chromosome banding by fluorescence in situ
      hybridization (FISH) showed PML-RARalpha, confirming the diagnosis of APL.
      Treatment with tretinoin was immediately initiated. No signs of recurrence have
      been noted 1 year after treatment. CONCLUSIONS: We report herein a rare case
      involving an infant with APL who presented with an extramedullary tumor of the
      mandible, whom we treated with good results.

PMID- 22972689
TI  - Repeated transfusions of autologous cytokine-induced killer cells for treatment
      of haematological malignancies in elderly patients: a pilot clinical trial.
AB  - The elderly population is susceptible to haematological malignancies, and these
      elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of
      a safe and reliable strategy exclusive of chemotherapy is critical in improving
      the prognosis of elderly patients with haematological malignancies. We evaluated
      the safety and the efficacy of autologous cytokine-induced killer (CIK) cells
      combined with recombinant human interleukin 2 (rhIL-2) in the treatment of
      haematological malignancies in elderly patients. Peripheral blood mononuclear
      cells were isolated from 20 elderly patients with haematological malignancies,
      then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal
      antibody. The autologous CIK cells (2-3 * 10(9)) were transfused back to
      patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10
      consecutive days. The regimen was repeated every 4 weeks. The host cellular
      immune function, tumour-related biological parameters, imaging characteristics,
      disease condition, quality of life and survival time were assessed. Fourteen
      patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse
      effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+)
      CD56(+) cells were significantly increased (p < 0.05), and the levels of serum
      beta2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p <
      0.05) after autologous CIK cell transfusion. Cancer-related symptoms were
      profoundly alleviated, as demonstrated by the improved quality of life (p <
      0.01). Complete remission was observed in 11 patients, persistent partial
      remission in 7 patients and stable disease in 2 patients. At the end of follow
      up, the mean survival time was 20 months. Transfusion with autologous CIK cells
      plus rhIL-2 treatment is safe and effective for treating haematological
      malignancies in elderly patients.

PMID- 22972691
TI  - Hydrogen bonds in galactopyranoside and glucopyranoside: a density functional
      theory study.
AB  - Density functional theory calculations on two glycosides, namely, n-octyl-beta-D
      glucopyranoside (C(8)O-beta-Glc) and n-octyl-beta-D-galactopyranoside (C(8)O-beta
      Gal) were performed for geometry optimization at the B3LYP/6-31G level. Both
      molecules are stereoisomers (epimers) differing only in the orientation of the
      hydroxyl group at the C4 position. Thus it is interesting to investigate
      electronically the effect of the direction (axial/equatorial) of the hydroxyl
      group at the C4 position. The structure parameters of X-H???Y intramolecular
      hydrogen bonds were analyzed, while the nature of these bonds and the
      intramolecular interactions were considered using the atoms in molecules (AIM)
      approach. Natural bond orbital analysis (NBO) was used to determine bond orders,
      charge and lone pair electrons on each atom and effective non-bonding
      interactions. We have also reported electronic energy and dipole moment in gas
      and solution phases. Further, the electronic properties such as the highest
      occupied molecular orbital, lowest unoccupied molecular orbital, ionization
      energy, electron affinity, electronic chemical potential, chemical hardness,
      softness and electrophilicity index, are also presented here for both C(8)O-beta
      Glc and C(8)O-beta-Gal. These results show that, while C(8)O-beta-Glc possess-
      only one hydrogen bond, C(8)O-beta-Gal has two intramolecular hydrogen bonds,
      which further confirms the anomalous stability of the latter in self-assembly
      phenomena.

PMID- 22972692
TI  - Insight on the interaction of polychlorobiphenyl with nucleic acid-base.
AB  - The interaction between one polychlorobiphenyl (3,3',4,4',-tetrachlorobiphenyl,
      coded PCB77) and the four DNA nucleic acid-base is studied by means of quantum
      mechanics calculations in stacked conformations. It is shown that even if the
      intermolecular dispersion energy is the largest component of the total
      interaction energy, some other contributions play a non negligible role. In
      particular the electrostatic dipole-dipole interaction and the charge transfer
      from the nucleobase to the PCB are responsible for the relative orientation of
      the monomers in the complexes. In addition, the charge transfer tends to flatten
      the PCB, which could therefore intercalate more easily between DNA base pairs.
      From these seminal results, we predict that PCB could intercalate completely
      between two base pairs, preferably between Guanine:Cytosine pairs.

PMID- 22972693
TI  - Isotope ratio mass spectrometry - history and terminology in brief.
AB  - The history of isotope ratio mass spectrometry (IRMS) is briefly described. It is
      shown that the fundamental design of isotope ratio mass spectrometers has not
      changed since the 1940s. The basic findings concerning the natural variation of
      isotope abundances even date back to the 1930s. Recent improvements in the
      methodology mainly concern online coupling and analytical peripherals. The nature
      of isotopic scales necessitates a specific terminology which is unfamiliar to
      many analysts. However, corresponding guidelines exist that should be adopted by
      the anti-doping community. Currently, steroids represent the only group of
      compounds routinely analyzed by IRMS in doping-control. Suggestions are made in
      respect to a harmonized terminology concerning the nature and origins of
      steroids.

PMID- 22972694
TI  - Analysis of Ki-67 expression with neoadjuvant anastrozole or tamoxifen in
      patients receiving goserelin for premenopausal breast cancer.
AB  - BACKGROUND: The increasing costs associated with large-scale adjuvant trials mean
      that the prognostic value of biologic markers is increasingly important. The
      expression of nuclear antigen Ki-67, a marker of cell proliferation, has been
      correlated with treatment efficacy and is being investigated for its value as a
      predictive marker of therapeutic response. In the current study, the authors
      explored correlations between Ki-67 expression and tumor response, estrogen
      receptor (ER) status, progesterone receptor (PgR) status, and histopathologic
      response from the STAGE study (S_tudy of T_amoxifen or A_rimidex, combined with
      G_oserelin acetate to compare E_fficacy and safety). METHODS: In a phase 3,
      double-blind, randomized trial (National Clinical Trials identifier NCT00605267),
      premenopausal women with ER-positive, early stage breast cancer received either
      anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before
      surgery. The Ki-67 index, hormone receptor (ER and PgR) status, and
      histopathologic responses were determined from histopathologic samples that were
      obtained from core-needle biopsies at baseline and at surgery. Tumor response was
      determined by using magnetic resonance imaging or computed tomography. RESULTS:
      In total, 197 patients were randomized to receive either anastrozole plus
      goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor
      response was better for the anastrozole group compared with the tamoxifen group
      both among patients who had a baseline Ki-67 index >=20% and among those who had
      a baseline Ki-67 index <20%. There was no apparent correlation between baseline
      ER status and the Ki-67 index in either group. Positive PgR status was reduced
      from baseline to week 24 in the anastrozole group. CONCLUSIONS: In premenopausal
      women with ER-positive breast cancer, anastrozole produced a greater best overall
      tumor response compared with tamoxifen regardless of the baseline Ki-67 index.

PMID- 22972695
TI  - Buried free flaps in head and neck surgery: outcome analysis.
AB  - BACKGROUND: Over the last several decades, reconstruction of the head and neck
      oncologic defect has been revolutionized by the use of microvascular free tissue
      transfer. The majority of these defects can be reconstructed with the ability to
      visually monitor the flap, to intervene as soon as vascular compromise becomes
      evident. Occasionally, it is necessary to use a flap that has no visual external
      monitor: a buried free flap. A belief has circulated within the microvascular
      community that buried free flaps do not do as well as visible flaps. By our
      review, there are no recent data in the literature to support this position. We
      present our data on the outcomes of buried free flaps in microvascular
      reconstruction. METHODS: A single institutional retrospective review of 1492
      flaps was performed between January 1999 and December 2011. A total of 103 free
      flaps (7.2%) were identified as meeting the criteria for a buried flap. It should
      be noted that all flaps with or without an external segment were monitored with
      an implantable Doppler. The flap failure and complications are defined as those
      failures or complications occurring within 2 weeks of surgery and related to the
      operation or to the flap itself. RESULTS: In all, 5 of the 103 patients (4.9%)
      had complications requiring reoperative intervention. There were no instances of
      flap failure within the first 2 weeks of surgery. CONCLUSION: In our series,
      there are no differences in flap failure rates comparing buried flaps to
      externally monitored flaps.

PMID- 22972696
TI  - Analysis and optimal design for association studies using next-generation
      sequencing with case-control pools.
AB  - With its potential to discover a much greater amount of genetic variation, next
      generation sequencing is fast becoming an emergent tool for genetic association
      studies. However, the cost of sequencing all individuals in a large-scale
      population study is still high in comparison to most alternative genotyping
      options. While the ability to identify individual-level data is lost (without bar
      coding), sequencing pooled samples can substantially lower costs without
      compromising the power to detect significant associations. We propose a
      hierarchical Bayesian model that estimates the association of each variant using
      pools of cases and controls, accounting for the variation in read depth across
      pools and sequencing error. To investigate the performance of our method across a
      range of number of pools, number of individuals within each pool, and average
      coverage, we undertook extensive simulations varying effect sizes, minor allele
      frequencies, and sequencing error rates. In general, the number of pools and pool
      size have dramatic effects on power while the total depth of coverage per pool
      has only a moderate impact. This information can guide the selection of a study
      design that maximizes power subject to cost, sample size, or other laboratory
      constraints. We provide an R package (hiPOD: hierarchical Pooled Optimal Design)
      to find the optimal design, allowing the user to specify a cost function, cost,
      and sample size limitations, and distributions of effect size, minor allele
      frequency, and sequencing error rate. 

PMID- 22972697
TI  - Cleft palate defect of Dlx1/2-/- mutant mice is caused by lack of vertical
      outgrowth in the posterior palate.
AB  - BACKGROUND: Mice lacking the activities of Dlx1 and Dlx2 (Dlx1/2-/-) exhibit
      cleft palate, one of the most common human congenital defects, but the etiology
      behind this phenotype has been unknown. Therefore, we analyzed the morphological,
      cellular, and molecular changes caused by inactivation of Dlx1 and Dlx2 as
      related to palate development. RESULTS: Dlx1/2-/- mutants exhibited lack of
      vertical growth in the posterior palate during the earliest stage of
      palatogenesis. We attributed this growth deficiency to reduced cell
      proliferation. Expression of a cell cycle regulator Ccnd1 was specifically down
      regulated in the same region. Previous studies established that the epithelial
      mesenchymal signaling loop involving Shh, Bmp4, and Fgf10 is important for cell
      proliferation and tissue growth during palate development. This signaling loop
      was disrupted in Dlx1/2-/- palate. Interestingly, however, the decreases in Ccnd1
      expression and mitosis in Dlx1/2-/- mutants were independent of this signaling
      loop. Finally, Dlx1/2 activity was required for normal expression of several
      transcription factor genes whose mutation results in palate defects. CONCLUSIONS:
      The functions of Dlx1 and Dlx2 are crucial for the initial formation of the
      posterior palatal shelves, and that the Dlx genes lie upstream of multiple
      signaling molecules and transcription factors important for later stages of
      palatogenesis.

PMID- 22972698
TI  - Fraction of unsaturated fatty acids in visceral adipose tissue (VAT) is lower in
      subjects with high total VAT volume - a combined 1 H MRS and volumetric MRI study
      in male subjects.
AB  - Visceral adipose tissue (VAT) is thought to play an important role in the
      pathogenesis of obesity and insulin resistance. However, little is known about
      the composition of VAT with regard to the amount of mono- (MUFAs) and
      polyunsaturated fatty acids (PUFAs) in triglycerides. Volume-selective MRS was
      performed in addition to MRI for the quantification of VAT. Analysis comprised
      proton signals from the vinyl-H group (H-C=C-H), including protons from
      MUFA+PUFA, and diallylic-H, i.e. methylene-interrupted PUFAs. The methyl (-CH(3)
      ) resonance, which is the only peak with a defined number of protons/triglyceride
      (n=9), served as reference. Twenty male subjects participated in this prospective
      study and underwent MRS of VAT on a 3-T whole-body unit. Spectra were recorded by
      a single-voxel stimulated echo acquisition mode (STEAM) technique
      (TE/TM/TR=20/10/4000 ms; volume of interest between 20 * 25 * 20 and 30 * 30 * 20
      mm(3); 48-80 acquisitions depending on the size of the volume of interest;
      bandwidth, 1200 Hz). Post-processing was performed by a Java-based magnetic
      resonance user interface (jMRUI; AMARES). The volume of VAT was quantified in a
      separate session on a 1.5-T imager a few days prior to the MRS session by T(1) 
      weighted imaging. The relative amount of VAT was calculated as a percentage of
      body weight (%VAT). Ratios of vinyl-H to -CH(3) and diallylic-H to -CH(3) were
      calculated. All spectra recorded from VAT were of high quality, enabling reliable
      quantification of the mentioned resonances. %VAT and vinyl-H/CH(3) varied over a
      broad range (2.8-8.3% and 0.45-0.64, respectively). A strong negative correlation
      between %VAT and vinyl-H/CH(3) was found (r= -0.92), whereas diallylic-H/CH(3)
      alone was clearly less well correlated with %VAT (r= -0.21). The composition of
      VAT shows strong interindividual variations. The greater the total amount of VAT,
      the less unsaturated the fatty acids. This is a preliminary result in mainly
      obese male subjects, and it remains to be determined whether this correlation
      holds for other cohorts of different age, gender and body mass index.
      Furthermore, changes in VAT composition during weight loss or different forms of
      diet have yet to be examined.

PMID- 22972699
TI  - Rebuttal: Reply to letter to the editor written by Fernandez-Pereira et al.

PMID- 22972700
TI  - Anatomy of the fully formed chondrocranium of Emydura subglobosa (Chelidae): a
      pleurodiran turtle.
AB  - The chondrocranium is a cartilaginous structure that forms around and protects
      the brain and sensory organs of the head. Through ontogeny, this skeletal
      structure may become more elaborate, remodeled and reabsorbed, and/or ossified.
      Though considerable attention has been given to the formation of the
      chondrocranium and a great amount of data has been gathered on the development of
      this structure among many craniates, the anatomy of this structure in turtles
      often is neglected. We describe the mature chondrocranium of the pleurodiran
      turtle, Emydura subglobosa (Chelidae) based on hatchling specimens. Though
      formation and ossification of bony elements has been studied previously in this
      species, a detailed description of the chondrocranium of this pleurodiran turtle
      has not been presented. Anatomy of the chondrocranium was described for E.
      subglobosa by examination of cleared and double-stained specimens. The
      orbitotemporal region of E. subglobosa is dramatically different from that of
      other described turtles (e.g., Apalone spinifera, Pelodiscus sinensis, Chelydra
      serpentina, Macrochelys temminckii, Trachemys scripta, Chrysemys picta, and
      Eretmochelys imbricata) in that a prominent taenia marginalis spans the space
      between the planum supraseptale and otic capsules, and the pila antotica (which
      becomes modified and ossified through ontogeny to form the processus clinoideus)
      is greatly reduced and essentially absent in hatchling specimens. The morphology
      seen in E. subglobosa is similar to that of Caretta caretta, particularly as it
      relates to the taenia marginalis. Variation in the orbitotemporal region is
      briefly discussed in the context of the taenia marginalis, taenia medialis, pila
      metoptica, and pila antotica.

PMID- 22972701
TI  - The solution properties of mefenamic acid and a closely related analogue are
      indistinguishable in polar solvents but significantly different in nonpolar
      environments.
AB  - This study investigates the cosolute effects of mefenamic acid (XA) and
      flufenamic acid (FA). These compounds serve as model of a drug discovery lead
      compound and a structural analogue. The activity coefficients of XA and FA in
      different solvents were obtained from solubility measurements at 25 degrees C.
      The effect of varying concentrations of FA on the solubility of XA in four
      different solvents, including toluene, cyclohexane, ethanol, and an ethanol-water
      mixture (80:20, v/v), was investigated. The magnitude of change in the activity
      coefficient of XA in the presence of FA in different solvents was used to
      elucidate the thermodynamic effect of FA on the solubility of XA. Nuclear
      magnetic resonance and Fourier-transform infrared spectroscopy were used to
      obtain molecular level information about the interactions of the compounds in
      solution. The presence of FA increases XA solubility in toluene and in
      cyclohexane as much as seven-fold. Conversely, in ethanol and the ethanol-water
      mixture, similar levels of FA have essentially no effect on the solubility of XA.
      The solution properties investigated show that despite the close structural
      similarity between XA and FA, the two compounds are strongly distinguishable in
      nonpolar solvents. Conversely, the solution properties of the same two solutes
      are indistinguishable in polar solvents. A solubilization model based on solute
      cosolute interactions is presented.

PMID- 22972702
TI  - Cannabis and psychomotor performance: a rational review of the evidence and
      implications for public policy.

PMID- 22972703
TI  - 1H-MR spectroscopy and diffusion tensor imaging of normal-appearing temporal
      white matter in patients with nasopharyngeal carcinoma after irradiation: initial
      experience.
AB  - PURPOSE: To detect radiation-induced changes of temporal lobe normal-appearing
      white mater (NAWM) following radiation therapy (RT) for nasopharyngeal carcinoma
      (NPC). MATERIALS AND METHODS: Seventy-five H(1)-MR spectroscopy and diffusion
      tensor imaging (DTI) examinations were performed in 55 patients before and after
      receiving fractionated radiation therapy (total dose; 66-75GY). We divided the
      dataset into six groups, a pre-RT control group and five other groups based on
      time after completion of RT. N-acetylaspartic acid (NAA)/choline (Cho),
      NAA/creatine (Cr), Cho/Cr, mean diffusibility (MD), functional anisotropy (FA),
      radial diffusibility (lambda(?)), and axial diffusibility (lambda(||)) were
      calculated. RESULTS: NAA/Cho and NAA/Cr decreased and lambda(?) increased
      significantly within 1 year after RT compared with pre-RT. After 1 year, NAA/Cho,
      NAA/Cr, and lambda(?) were not significantly different from pre-RT. In all post
      RT groups, FA decreased significantly. lambda(||) decreased within 9 months after
      RT compared with pre-RT, but was not significantly different from pre-RT more
      than 9 months after RT. CONCLUSION: DTI and H(1)-MR spectroscopy can be used to
      detect early radiation-induced changes of temporal lobe NAWM following radiation
      therapy for NPC. Metabolic alterations and water diffusion characteristics of
      temporal lobe NAWM in patients with NPC after RT were dynamic and transient.

PMID- 22972704
TI  - Climate change: resetting plant-insect interactions.

PMID- 22972707
TI  - Epigenetic landscape and miRNA involvement during neural crest development.
AB  - The neural crest (NC) is a multipotent, migratory cell population that arises
      from the dorsal neural fold of vertebrate embryos. NC cells migrate extensively
      and differentiate into a variety of tissues, including melanocytes, bone, and
      cartilage of the craniofacial skeleton, peripheral and enteric neurons, glia, and
      smooth muscle and endocrine cells. For several years, the gene regulatory network
      that orchestrates NC cells development has been extensively studied. However, we
      have recently begun to understand that epigenetic and posttranscriptional
      regulation, such as miRNAs, plays important roles in NC development. In this
      review, we focused on some of the most recent findings on chromatin-dependent
      mechanisms and miRNAs regulation during vertebrate NC cells development.

PMID- 22972705
TI  - Microbe-associated molecular patterns-triggered root responses mediate beneficial
      rhizobacterial recruitment in Arabidopsis.
AB  - This study demonstrated that foliar infection by Pseudomonas syringae pv tomato
      DC3000 induced malic acid (MA) transporter (ALUMINUM-ACTIVATED MALATE
      TRANSPORTER1 [ALMT1]) expression leading to increased MA titers in the
      rhizosphere of Arabidopsis (Arabidopsis thaliana). MA secretion in the
      rhizosphere increased beneficial rhizobacteria Bacillus subtilis FB17 (hereafter
      FB17) titers causing an induced systemic resistance response in plants against P.
      syringae pv tomato DC3000. Having shown that a live pathogen could induce an
      intraplant signal from shoot-to-root to recruit FB17 belowground, we hypothesized
      that pathogen-derived microbe-associated molecular patterns (MAMPs) may relay a
      similar response specific to FB17 recruitment. The involvement of MAMPs in
      triggering plant innate immune response is well studied in the plant's response
      against foliar pathogens. In contrast, MAMPs-elicited plant responses on the
      roots and the belowground microbial community are not well understood. It is
      known that pathogen-derived MAMPs suppress the root immune responses, which may
      facilitate pathogenicity. Plants subjected to known MAMPs such as a flagellar
      peptide, flagellin22 (flg22), and a pathogen-derived phytotoxin, coronatine
      (COR), induced a shoot-to-root signal regulating ALMT1 for recruitment of FB17.
      Micrografts using either a COR-insensitive mutant (coi1) or a flagellin
      insensitive mutant (fls2) as the scion and ALMT1(pro):beta-glucuronidase as the
      rootstock revealed that both COR and flg22 are required for a graft transmissible
      signal to recruit FB17 belowground. The data suggest that MAMPs-induced signaling
      to regulate ALMT1 is salicylic acid and JASMONIC ACID RESISTANT1 (JAR1)/JASMONATE
      INSENSITIVE1 (JIN1)/MYC2 independent. Interestingly, a cell culture filtrate of
      FB17 suppressed flg22-induced MAMPs-activated root defense responses, which are
      similar to suppression of COR-mediated MAMPs-activated root defense, revealing a
      diffusible bacterial component that may regulate plant immune responses. Further
      analysis showed that the biofilm formation in B. subtilis negates suppression of
      MAMPs-activated defense responses in roots. Moreover, B. subtilis suppression of
      MAMPs-activated root defense does require JAR1/JIN1/MYC2. The ability of FB17 to
      block the MAMPs-elicited signaling pathways related to antibiosis reflects a
      strategy adapted by FB17 for efficient root colonization. These experiments
      demonstrate a remarkable strategy adapted by beneficial rhizobacteria to suppress
      a host defense response, which may facilitate rhizobacterial colonization and
      host-mutualistic association.

PMID- 22972708
TI  - Revised structures of avenacosides A and B and a new sulfated saponin from Avena
      sativa L.
AB  - The revised structures of avenacosides A and B and a new sulfated steroidal
      saponin isolated from grains of Avena sativa L. were elucidated. Their structures
      and complete NMR assignments are based on 1D and 2D NMR studies and identified as
      nuatigenin 3-O-{alpha-L-rhamnopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->4)]
      beta-D-glucopyranoside}-26-O-beta-D-glucopyranoside (1), nuatigenin 3-O-{alpha-L
      rhamnopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)-beta-D-glucopyranosyl-(1
      >4)]-beta-D-glucopyranoside}-26-O-beta-D-glucopyranoside (2), and nuatigenin 3-O
      {alpha-L-rhamnopyranosyl-(1->2)-[beta-D-6-O-sulfoglucopyranosyl-(1->4)]-beta-D
      glucopyranoside}-26-O-beta-D-glucopyranoside (3).

PMID- 22972706
TI  - Maize source leaf adaptation to nitrogen deficiency affects not only nitrogen and
      carbon metabolism but also control of phosphate homeostasis.
AB  - Crop plant development is strongly dependent on the availability of nitrogen (N)
      in the soil and the efficiency of N utilization for biomass production and yield.
      However, knowledge about molecular responses to N deprivation derives mainly from
      the study of model species. In this article, the metabolic adaptation of source
      leaves to low N was analyzed in maize (Zea mays) seedlings by parallel
      measurements of transcriptome and metabolome profiling. Inbred lines A188 and B73
      were cultivated under sufficient (15 mM) or limiting (0.15 mM) nitrate supply for
      up to 30 d. Limited availability of N caused strong shifts in the metabolite
      profile of leaves. The transcriptome was less affected by the N stress but showed
      strong genotype- and age-dependent patterns. N starvation initiated the selective
      down-regulation of processes involved in nitrate reduction and amino acid
      assimilation; ammonium assimilation-related transcripts, on the other hand, were
      not influenced. Carbon assimilation-related transcripts were characterized by
      high transcriptional coordination and general down-regulation under low-N
      conditions. N deprivation caused a slight accumulation of starch but also
      directed increased amounts of carbohydrates into the cell wall and secondary
      metabolites. The decrease in N availability also resulted in accumulation of
      phosphate and strong down-regulation of genes usually involved in phosphate
      starvation response, underlining the great importance of phosphate homeostasis
      control under stress conditions.

PMID- 22972709
TI  - Hierarchical non-negative matrix factorization (hNMF): a tissue pattern
      differentiation method for glioblastoma multiforme diagnosis using MRSI.
AB  - MRSI has shown potential in the diagnosis and prognosis of glioblastoma
      multiforme (GBM) brain tumors, but its use is limited by difficult data
      interpretation. When the analyzed MRSI data present more than two tissue
      patterns, conventional non-negative matrix factorization (NMF) implementation may
      lead to a non-robust estimation. The aim of this article is to introduce an
      effective approach for the differentiation of GBM tissue patterns using MRSI
      data. A hierarchical non-negative matrix factorization (hNMF) method that can
      blindly separate the most important spectral sources in short-TE 1H MRSI data is
      proposed. This algorithm consists of several levels of NMF, where only two tissue
      patterns are computed at each level. The method is demonstrated on both simulated
      and in vivo short-TE 1H MRSI data in patients with GBM. For the in vivo study,
      the accuracy of the recovered spectral sources was validated using expert
      knowledge. Results show that hNMF is able to accurately estimate the three tissue
      patterns present in the tumoral and peritumoral area of a GBM, i.e. normal, tumor
      and necrosis, thus providing additional useful information that can help in the
      diagnosis of GBM. Moreover, the hNMF results can be displayed as easily
      interpretable maps showing the contribution of each tissue pattern to each voxel.

PMID- 22972710
TI  - Study on the ternary system of MoO4 (2-) -enzyme-PdCl2 by resonance Rayleigh
      scattering, second-order scattering and frequency-doubling scattering spectra and
      its analytical application.
AB  - In pH 4.0 Britton-Robinson buffer medium, PdCl2 was able to react with enzymes
      (EZ) such as lysozyme (LYSO) and papain (PAP) to form a coordination complex (EZ
      PdCl2 ), which further reacted with MoO4 (2-) to form a ternary complex (MoO4 (2
      ) -EZ-PdCl2 ). As a result, the absorption and fluorescence spectra changed; new
      spectra of resonance Rayleigh scattering (RRS), second-order scattering (SOS) and
      frequency-doubling scattering (FDS) appeared and their intensities were enhanced
      greatly. The maximum RRS, SOS and FDS wavelengths of two ternary complexes were
      located at 310, 560 and 350 nm, respectively. The increments of scattering
      intensity were directly proportional to the concentrations of EZ within certain
      ranges. The detection limits (3sigma) of LYSO and PAP were 4.5 and 14.0 ng/mL
      (RRS method), 9.6 and 57.8 ng/mL (SOS method), and 5.2 and 106.0 ng/mL (FDS
      method). Taking the MoO4 (2-) -LYSO-PdCl2 system, which was more sensitive, as an
      example, the effects of coexisting substances were evaluated. The methods showed
      excellent selectivity. Accordingly, new rapid, convenient, sensitive and
      selective scattering methods for the determination of LYSO and PAP were proposed
      and applied to determine LYSO in egg white with satisfactory results. The
      reaction mechanism and basis of the enhancement of scattering were discussed.

PMID- 22972711
TI  - Accuracy of intraoperative frozen margins for sinonasal malignancies and its
      implications for endoscopic resection of sinonasal melanomas.
AB  - BACKGROUND: The main objective of endoscopic tumor surgery remains similar to
      open approaches, with the goal being total tumor resection with clear margins.
      Beyond cosmesis, endoscopes offer the advantage of limiting the size of the
      resection as well as aiding in the procurement of tissue margins in areas
      adjacent to critical structures or deep in the sinonasal cavity. Because of the
      close proximity of these tumors to critical structures and classic otolaryngology
      teaching with the goal sparing normal sinonasal mucosa, sinonasal tumor resection
      margins tend to be more conservative than those practiced for the same type of
      tumor in a different anatomic location. What is not uniformly agreed upon is the
      optimal margin of resection as well as the reliability of intraoperative frozen
      margins for the varied histologic subtypes seen in sinonasal malignancies.
      METHODS: Retrospective review of malignant sinonasal tumors resected
      endoscopically by 1 surgeon at 2 institutions between 2006 and 2011. RESULTS:
      Thirty-one patients with mixed histologies were identified, with the most common
      being mucosal melanoma (25.8%) and squamous cell carcinoma (23.3%). The overall
      false-negative rate for intraoperative frozen margins was 6.5%, with both false
      negatives associated with mucosal melanoma. The false-negative margin rate for
      mucosal melanoma was 25%. CONCLUSION: Intraoperative frozen margins for sinonasal
      tumors are reliable for most histologic subtypes, with the exception of those for
      sinonasal mucosal melanomas. This has implications for the size of margins needed
      for the resection of sinonasal melanomas as they may need to be larger than those
      for other tumors.

PMID- 22972712
TI  - Development of the olfactory and vomeronasal organs in Discoglossus pictus
      (Discoglossidae, Anura).
AB  - Using histological techniques and computer-aided three-dimensional
      reconstructions of histological serial sections, we studied the development of
      the olfactory and vomeronasal organs in the discoglossid frog Discoglossus
      pictus. The olfactory epithelium in larval D. pictus represents one continuous
      unit of tissue not divided into two separate portions. However, a small pouch of
      olfactory epithelium (the "ventromedial diverticulum") is embedded into the roof
      of the buccal cavity, anteromedial to the internal naris. The lateral appendix is
      present in D. pictus through the entire larval period and disappears during the
      onset of metamorphosis. The disappearance of the lateral appendix at this time
      suggests that it is a typical larval organ related to aquatic life. The
      vomeronasal organ develops during hindlimb development, which is comparatively
      late for anurans. The development of the vomeronasal organ in D. pictus follows
      the same general developmental pattern recognized for neobatrachians. As with
      most anurans, the vomeronasal glands appear later than the vomeronasal organ.
      After metamorphosis, the olfactory organ of adult D. pictus is composed of a
      series of three interconnected chambers: the cavum principale, cavum medium, and
      cavum inferius. We suggest that the ventromedial diverticulum at the anterior
      border of the internal naris of larval D. pictus might be homologous with the
      ventral olfactory epithelium of bufonids and with the similar diverticulum of
      Alytes.

PMID- 22972713
TI  - Evaluation of phase-sensitive versus magnitude reconstructed inversion recovery
      imaging for the assessment of myocardial infarction in mice with a clinical
      magnetic resonance scanner.
AB  - PURPOSE: To evaluate phase-sensitive inversion-recovery (PSIR) imaging at 1.5 T
      in a mouse model of permanent coronary artery ligation as a potentially rapid and
      robust alternative for the accurate assessment of myocardial infarction (MI) by
      cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: PSIR late
      gadolinium enhancement (LGE) imaging was compared to conventional 2D segmented
      inversion-recovery imaging for the assessment of murine MI. RESULTS: PSIR images
      provided comparable contrast and kinetics of intravenously injected gadopentetate
      dimeglumine (Gd-DTPA). At the mid-ventricular level there was good agreement
      between conventional IR and PSIR for infarct size assessment. After intravenous
      injection a limited time window of ~6 minutes is available for delayed
      enhancement imaging in mice. Whole-heart infarct imaging with 1 mm thick slices
      was only possible in this restricted time frame when the PSIR method is applied,
      avoiding the need for repetitively adapting the correct inversion time. Infarct
      size determined by PSIR MRI demonstrated good agreement with postmortem
      histology. Infarct size determined by PSIR LGE MRI inversely correlates with left
      ventricular function on day 7 after MI. CONCLUSION: The PSIR technique provides
      stable and consistent contrast between hyperenhanced and remote myocardium
      independent of the selected inversion time (TI) and proved to be a robust, fast,
      and accurate tool for the assessment of MI in mice.

PMID- 22972714
TI  - Formulation and in vitro/in vivo correlation of a drug-in-adhesive transdermal
      patch containing azasetron.
AB  - The aim of the present study was to develop a transdermal drug delivery system
      for azasetron and evaluate the correlation between in vitro and in vivo release.
      The effects of different adhesives, permeation enhancers, and loadings of
      azasetron used in patches on the penetration of azasetron through rabbit skin
      were investigated using two-chamber diffusion cells in vitro. For in vivo
      studies, azasetron pharmacokinetic parameters in Bama miniature pigs were
      determined according to a noncompartment model method after topical application
      of transdermal patches and intravenous administration of azasetron injections.
      The best permeation profile was obtained with the formulation containing DURO-TAK
      87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of
      azasetron. The optimal patch formulation exhibited sustained release profiles in
      vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by
      deconvolution approach using WinNonlin(r) program was correlated well with the in
      vitro permeation curve of the azasetron patch. These findings indicated that the
      developed patch for azasetron is promising for the treatment of delayed
      chemotherapy-induced nausea and vomiting, and the in vitro skin permeation
      experiments could be useful to predict the in vivo performance of transdermal
      azasetron patches.

PMID- 22972716
TI  - Severe skeletal toxicity from protracted etidronate therapy for generalized
      arterial calcification of infancy.
AB  - Generalized arterial calcification (AC) of infancy (GACI) is an autosomal
      recessive disorder that features hydroxyapatite deposition within arterial
      elastic fibers. Untreated, approximately 85% of GACI patients die by 6 months of
      age from cardiac ischemia and congestive heart failure. The first-generation
      bisphosphonate etidronate (EHDP; ethane-1-hydroxy-1,1-diphosphonic acid, also
      known as 1-hydroxyethylidene-bisphosphonate) inhibits bone resorption and can
      mimic endogenous inorganic pyrophosphate by blocking mineralization. With EHDP
      therapy for GACI, AC may resolve without recurrence upon treatment cessation.
      Skeletal disease is not an early characteristic of GACI, but rickets can appear
      from acquired hypophosphatemia or prolonged EHDP therapy. We report a 7-year-old
      boy with GACI referred for profound, acquired, skeletal disease. AC was gone
      after 5 months of EHDP therapy during infancy, but GACI-related joint
      calcifications progressed. He was receiving EHDP, 200 mg/day orally, and had
      odynodysphagia, diffuse opioid-controlled pain, plagiocephaly, facial
      dysmorphism, joint calcifications, contractures, and was wheelchair bound.
      Biochemical parameters of mineral homeostasis were essentially normal. Serum
      osteocalcin was low and the brain isoform of creatine kinase and tartrate
      resistant acid phosphatase 5b (TRAP-5b) were elevated as in osteopetrosis.
      Skeletal radiographic findings resembled pediatric hypophosphatasia with
      pancranial synostosis, long-bone bowing, widened physes, as well as metaphyseal
      osteosclerosis, cupping and fraying, and "tongues" of radiolucency. Radiographic
      features of osteopetrosis included osteosclerosis and femoral Erlenmeyer flask
      deformity. After stopping EHDP, he improved rapidly, including remarkable
      skeletal healing and decreased joint calcifications. Profound, but rapidly
      reversible, inhibition of skeletal mineralization with paradoxical calcifications
      near joints can occur in GACI from protracted EHDP therapy. Although EHDP
      treatment is lifesaving in GACI, surveillance for toxicity is crucial.

PMID- 22972717
TI  - First, do no harm.

PMID- 22972715
TI  - Membrane beta-catenin and adherens junctions in early gonadal patterning.
AB  - BACKGROUND: Mechanisms involved in early patterning of the mammalian gonad as it
      develops from a bipotential state into a testis or an ovary are as yet not well
      understood. Sex-specific vascularization is essential in this process, but more
      specific mechanisms required to, for example, establish interstitial vs. cord
      compartments in the testis or ovigerous cords in the ovary have not been
      reported. Adherens junctions (AJs) are known for their roles in morphogenesis;
      we, therefore, examined expression of AJ components including beta-catenin, p120
      catenin, and cadherins for possible involvement in sex-specific patterning of the
      gonad. RESULTS: We show that, at the time of early gonadal sex differentiation,
      membrane-associated beta-catenin and p120 catenin colocalize with cell-specific
      cadherins in both sex-nonspecific and sex-specific patterns. These expression
      patterns are consistent with an influence of AJs in overall patterning of the
      testis vs. ovary through known AJ mechanisms of cell-cell adhesion, cell sorting,
      and boundary formation. CONCLUSIONS: Together these complex and dynamic patterns
      of AJ component expression precisely mirror patterning of tissues during
      gonadogenesis and raise the possibility that AJs are essential effectors of
      patterning within the developing testis and ovary.

PMID- 22972718
TI  - Food for thought ... and health: making a case for plant-based nutrition.

PMID- 22972719
TI  - Connecting orphan patients with family physicians: differences among Quebec's
      access registries.

PMID- 22972720
TI  - Burnout or mismatch between expectations and reality?

PMID- 22972721
TI  - Encouraging successful weight management.

PMID- 22972723
TI  - Health Canada advisory on domperidone should I avoid prescribing domperidone to
      women to increase milk production [corrected]?
AB  - QUESTION: I often prescribe domperidone to women as a galactagogue starting at a
      dose of 30 mg and increasing the dose as needed. In March of this year, Health
      Canada released an advisory warning of domperidone use and abnormal heart rhythms
      and sudden cardiac death. Should I cap doses at 30 mg or stop prescribing
      domperidone all together to these women? ANSWER: The Health Canada warning is
      based on 2 studies. The results of the studies are not directly applicable to
      breastfeeding and should not change the way you normally manage otherwise healthy
      breastfeeding women.

PMID- 22972722
TI  - Are medication restrictions before FOBT necessary?: practical advice based on a
      systematic review of the literature.
AB  - OBJECTIVE: To determine whether medication interventions enhance the sensitivity
      and specificity of guaiac-based fecal occult blood testing (FOBT) when screening
      for colorectal cancer (CRC). DATA SOURCES: We searched PubMed-MEDLINE, CINAHL,
      and the Cochrane databases using the MeSH headings occult blood, feces/analysis,
      and guaiac/analysis, linking them to variations of anticoagulants, heparin,
      warfarin, iron, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs),
      clopidogrel, cyclooxygenase-2 inhibitors, and ascorbic acid (vitamin C). Study
      selections were limited to English studies involving humans. STUDY SELECTION: All
      resulting titles and abstracts were reviewed for studies that included
      manipulation of medications associated with guaiac-based FOBT. If the study's
      relevance was unclear from the abstract, the full article was reviewed. The
      search resulted in 31 pertinent studies. SYNTHESIS: No studies addressed the
      effects of medication interventions on the sensitivity or specificity of FOBT
      screening. Randomized controlled trials, however, showed no increase in the rate
      of positive results among those taking NSAIDs. The literature is mixed regarding
      the effect of NSAIDs on the positive predictive value of a positive FOBT result,
      although no change in positive predictive value has been shown for warfarin. Iron
      will not affect FOBT results in vivo. Ascorbic acid might inhibit positive FOBT
      results both in vitro and in vivo, but it has not been studied in screening
      populations. CONCLUSION: Studies evaluating the effects of medication
      intervention on FOBT screening for CRC are limited by their lower quality and
      because they do not address sensitivity and specificity. Available evidence,
      however, does not suggest a benefit from withholding NSAIDs, anticoagulant
      medications, or iron during the screening period. These recommendations should be
      abandoned in order to maximize adherence to screening. Positive FOBT results
      obtained among patients taking these medications deserve full evaluation for CRC.
      Until further studies clarify the effect of ascorbic acid on FOBT screening,
      withholding this medication before testing seems prudent.

PMID- 22972724
TI  - Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infections.
AB  - QUESTION: I have heard about children who have tic disorders that seem to be
      exacerbated by group A beta-hemolytic streptococcal infection. Should children
      presenting with this phenomenon receive treatment with antibiotics, receive
      prophylactic treatment, or use immunomodulators to treat the symptoms? ANSWER:
      Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infections (PANDAS) constitute a condition that includes neuropsychiatric
      symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally
      associated with an immune-mediated response to streptococcal infections. The
      actual existence of PANDAS as a unique clinical entity is still up for debate, as
      a temporal association between group A beta-hemolytic streptococcal infections
      and symptom exacerbations has been difficult to prove thus far. Based on only a
      few studies, positive results have been found using antibiotic prophylaxis and
      immunomodulatory therapy in children with PANDAS. At this time, however, evidence
      does not support a recommendation for long-term antibiotic prophylaxis or
      immunomodulatory therapy.

PMID- 22972725
TI  - Management of critical limb ischemia.

PMID- 22972726
TI  - Taking blood pressure-lowering medications at night.

PMID- 22972727
TI  - Merkel cell carcinoma.

PMID- 22972728
TI  - Physical activity for cancer patients: clinical risk assessment for exercise
      clearance and prescription.

PMID- 22972729
TI  - Top 10 forgotten diagnostic procedures.

PMID- 22972730
TI  - Wood lamp examination.

PMID- 22972731
TI  - Dermacase. Can you identify this condition? Sarcoidosis.

PMID- 22972732
TI  - Cancer screening practices of cancer survivors: population-based, longitudinal
      study.
AB  - OBJECTIVE: To describe cancer screening rates for cancer survivors and compare
      them with those for matched controls. DESIGN: Population-based, retrospective
      study with individuals linked across administrative databases. SETTING: Ontario.
      PARTICIPANTS: Survivors of breast (n = 11 219), colorectal (n = 4348), or
      endometrial (n = 3473) cancer, or Hodgkin lymphoma (HL) (n = 2071) matched to
      general population controls. Survivors were those who had completed primary
      treatment and were on "well" follow-up. The study period was 4 years (1 to 5
      years from the date of cancer diagnosis). MAIN OUTCOME MEASURES: Never versus
      ever screened (in the 4-year study period) for breast cancer, colorectal cancer
      (CRC), and cervical cancer and never versus ever received (during the study
      period) a periodic health examination; rates were compared between cancer
      survivors and controls. Random effects models were used to estimate odds ratios
      and 95% CIs. RESULTS: Sixty-five percent of breast cancer survivors were never
      screened for CRC and 40% were never screened for cervical cancer. Approximately
      50% of CRC survivors were never screened for breast or cervical cancer. Thirty
      two percent of endometrial cancer survivors were never screened for breast cancer
      and 66% were never screened for CRC. Forty-four percent of HL survivors were
      never screened for breast cancer, 77% were never screened for CRC, and 32% were
      never screened for cervical cancer. Comparison with matched controls showed a
      mixed picture, with breast and endometrial cancer survivors more likely, and CRC
      and HL survivors less likely, than controls to be screened. CONCLUSION: There is
      concern about the preventive care of cancer survivors despite frequent visits to
      both oncology specialists and family physicians during the "well" follow-up
      period.

PMID- 22972733
TI  - Whose difficulty is it?

PMID- 22972734
TI  - Jean-Pierre Hamel MD.

PMID- 22972735
TI  - The scholarly path: ten lessons learned about scholarly activity from a
      sabbatical year.

PMID- 22972736
TI  - First Five Years in Family Practice initiative.

PMID- 22972737
TI  - It's about time: 3-year FM residency training.

PMID- 22972739
TI  - Effect of yoga on patients with cancer: our current understanding.
AB  - OBJECTIVE: To determine whether therapeutic yoga improves the quality of life of
      patients with cancer. DATA SOURCES: Search of MEDLINE database (1950-2010) using
      key words yoga, cancer, and quality of life. STUDY SELECTION: Priority was given
      to randomized controlled clinical studies conducted to determine the effect of
      yoga on typical symptoms of patients with cancer in North America. SYNTHESIS:
      Initially, 4 randomized controlled clinical studies were analyzed, then 2 studies
      without control groups were analyzed. Three studies conducted in India and the
      Near East provided interesting information on methodologies. The interventions
      included yoga sessions of varying length and frequency. The parameters measured
      also varied among studies. Several symptoms improved substantially with yoga
      (higher quality of sleep, decrease in symptoms of anxiety and depression,
      improvement in spiritual well-being, etc). It would appear that quality of life,
      or some aspects thereof, also improved. CONCLUSION: The variety of benefits
      derived, the absence of side effects, and the cost-benefit ratio of therapeutic
      yoga make it an interesting alternative for family physicians to suggest to their
      patients with cancer. Certain methodologic shortcomings, including the limited
      size of the samples and varying levels of attendance on the part of the subjects,
      might have reduced the statistical strength of the studies presented. It is also
      possible that the measurement scales used did not suit this type of situation and
      patient population, making it impossible to see a significant effect. However,
      favourable comments by participants during the studies and their level of
      appreciation and well-being suggest that further research is called for to fully
      understand the mechanisms of these effects.

PMID- 22972740
TI  - Factors associated with delays to medical assessment and diagnosis for patients
      with colorectal cancer.
AB  - OBJECTIVE: To identify factors associated with delays to medical assessment and
      diagnosis for patients with colorectal cancer (CRC). DESIGN: Data were collected
      through a standardized questionnaire. Clinical records were also reviewed. When
      necessary, patients were contacted by a member of the study team to collect
      missing data and confirm information. SETTING: Cross Cancer Institute in
      Edmonton, Alta. PARTICIPANTS: Patients newly diagnosed with a histologically
      proven colorectal adenocarcinoma were identified and eligible for the study. MAIN
      OUTCOME MEASURES: Associations between symptoms, tumour stage at operation,
      symptom duration, and tumour location were sought to identify factors associated
      with a delay in diagnosis of CRC. RESULTS: Surveys were completed by 93 patients.
      A total of 49% of patients had symptoms of CRC present for 1 month or less before
      seeing a physician, and 51% had symptoms for longer than 1 month. Seventy-five
      (86%) patients initially presented to family physicians for assessment, while 12
      (14%) patients presented to the emergency department for their first physician
      encounters. Only 33 (38%) patients had digital rectal examinations during their
      first visits. Women were more likely to present to physicians with longer than 1
      month of symptoms, while men were more likely to present with less than 1 month
      of symptoms (P = .03). Abdominal pain, blood in the stool, and change in stool
      size were the most frequent symptoms encountered. Twenty-two (26%) patients
      delayed seeking treatment because they thought their symptoms were not serious
      and 12 (14%) believed that their family physicians had taken inappropriate
      action. Fifteen (18%) patients attributed their delays to waiting too long for
      specialist referral and diagnostic tests. CONCLUSION: This study highlights the
      important role patients and physicians both play in delays in the diagnosis of
      CRC. Efforts to diminish future delays must focus on educating the public and
      practising physicians about important symptoms and signs of CRC. Additionally,
      the value of a digital rectal examination must be emphasized, along with
      continued promotion of CRC screening.

PMID- 22972741
TI  - Exploring patient perceptions of PSA screening for prostate cancer: risks,
      effectiveness, and importance.
AB  - OBJECTIVE: To study the beliefs of a group of Canadian men regarding the risks,
      effectiveness, and importance of routine prostate-specific antigen (PSA) testing
      when used as a screening tool for prostate cancer. DESIGN: A 1-page questionnaire
      designed to gauge patient beliefs about PSA screening. SETTING: Two primary care
      clinics in Kingston, Ont. PARTICIPANTS: Seventy-two men aged 41 to 80. MAIN
      OUTCOME MEASURES: Whether men believed that the PSA blood test was not risky when
      used as a screening test for prostate cancer, was effective at preventing death
      from prostate cancer, and was important for their health. RESULTS: Fifteen men
      reported having visited their physicians because of difficulty urinating in the
      past 2 years, or a personal history of prostate cancer, and were excluded; for
      these men, the use of the PSA blood test would not be for screening. Of the 57
      men considered in the study, 54 (95%) believed that using the PSA blood test as a
      screening tool for prostate cancer was not risky, 39 (68%) believed that the PSA
      blood test was good or very good at preventing death from prostate cancer, and 45
      (79%) believed that the routine use of the PSA blood test was important or very
      important for their health. Men in the suggested screening age group of 51 to 70
      years (n = 32) had an equally positive impression of PSA screening. CONCLUSION:
      Despite a limited body of evidence showing its effectiveness, Canadian men
      continue to have a favourable impression of PSA screening and remain largely
      unaware of potential adverse events associated with PSA testing.

PMID- 22972742
TI  - Physicians' attitudes and behaviour toward screening mammography in women 40 to
      49 years of age.
AB  - OBJECTIVE: To determine family physicians' attitudes and behaviour toward
      screening mammography, breast self-examination, and breast awareness in women
      aged 40 to 49 at average risk of breast cancer. DESIGN: Cross-sectional survey.
      SETTING: Women's College Hospital and Sunnybrook Health Sciences Centre, both in
      Toronto, Ont. PARTICIPANTS: Family medicine residents, fellows, and staff
      physicians at 2 academic family practice health centres affiliated with the
      University of Toronto (n = 95). MAIN OUTCOME MEASURES: Physicians' answers to
      questions about offering screening mammography and promoting breast self
      examination and breast awareness. RESULTS: Fifty-two completed surveys were
      returned (response rate 55%). Less than half of all surveyed family physicians
      (46%) routinely offered screening mammography to women aged 40 to 49 who were at
      average risk of breast cancer. Although 40% of physicians did not think breast
      cancer screening was necessary for women aged 40 to 49, 62% indicated that they
      would offer screening if their patients requested it. Physicians' reasons not to
      offer screening included no evidence of decreasing breast cancer deaths (63%),
      grade A recommendation to screen women starting at age 50 and not at age 40
      (25%), and the harms of screening outweighing the benefits (19%). Physicians'
      reasons to offer screening included patient request (55%), personal clinical
      practice experience or mentors' recommendations (27%), and guideline
      recommendations (18%). Breast self-examination was not recommended by most
      physicians (74%), yet most encouraged women to practise breast awareness (81%).
      CONCLUSION: Many women at average risk of breast cancer are not being offered the
      opportunity to discuss and initiate mammographic screening before 50 years of
      age. While breast-self examination is not recommended, most physicians promote
      breast awareness.

PMID- 22972743
TI  - Establishing physician advocates for human papillomavirus vaccination in British
      Columbia.
AB  - OBJECTIVE: To survey general practitioners in oncology (GPOs) in British Columbia
      (BC) to identify opportunities for them to serve as public supporters of human
      papillomavirus (HPV) vaccination. DESIGN: A mailed or online survey. SETTING:
      British Columbia. PARTICIPANTS: Forty-two GPOs who worked in the community in BC.
      MAIN OUTCOME MEASURES: Current practices, knowledge, and resource needs
      concerning HPV, the vaccine, and the HPV immunization program, and the
      willingness of respondents to be contacted to participate in stated public HPV
      vaccine supporter activities. RESULTS: The survey found that 42% of surveyed GPOs
      were willing to act as public supporters of the HPV vaccine. The survey also
      identified education needs among GPOs concerning HPV, the vaccine, and the HPV
      immunization program in BC. CONCLUSION: This study found that GPOs in BC are
      willing to publicly support the HPV immunization program. This study shows that
      involving physicians in the promotion of public health programs is a viable
      option that should be further explored and evaluated.

PMID- 22972744
TI  - Cervical cancer screening among vulnerable women: factors affecting guideline
      adherence at a community health centre in Toronto, Ont.
AB  - OBJECTIVE: To see if refugee women at a community health centre (CHC) in Toronto,
      Ont, are appropriately screened for cervical cancer and if there are any
      demographic characteristics that affect whether they are screened. DESIGN: Chart
      review. SETTING: A CHC in downtown Toronto. PARTICIPANTS: A total of 357 eligible
      refugee women attending the CHC. MAIN OUTCOME MEASURES: Papanicolaou test
      received or documented reason for no Pap test. RESULTS: Ninety-two percent of
      women in the study sample were either appropriately screened for cervical cancer
      or had been approached for screening. Eighty percent of women were appropriately
      screened. Demographic variables including pregnancy, being uninsured, not
      speaking English, recent migration to Canada, and being a visible minority did
      not affect receipt of a Pap test after migration in multivariate analyses. Not
      speaking English was associated with a delay to receiving a first Pap test after
      migration. CONCLUSION: The clients at our centre are demographically similar to
      women who are typically overlooked for Pap tests in the greater Toronto area.
      Despite belonging to a high-risk population, refugee women in this
      multidisciplinary CHC were screened for cervical cancer at a higher rate than the
      local population.

PMID- 22972745
TI  - Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying
      antirheumatic drugs: twenty-four-week results of an open-label, clinical practice
      study.
AB  - OBJECTIVE: To assess the safety and tolerability of tocilizumab (TCZ) as
      monotherapy or in combination with nonbiologic disease-modifying antirheumatic
      drugs (DMARDs) in patients with moderate to severe rheumatoid arthritis (RA) who
      had an inadequate response at study entry to their current treatment with
      biologic agents or DMARDs. METHODS: This 24-week, multicenter, open-label, phase
      IIIb study conducted in the US enrolled 886 patients. Treatments were allocated
      to patients based on their current therapy at study entry. Patients receiving
      monotherapy with biologic agents were assigned to TCZ 8 mg/kg monotherapy. All
      other patients were randomized to either TCZ 4 mg/kg + DMARDs or TCZ 8 mg/kg +
      DMARDs. The primary end point was the number and percentage of patients with
      serious adverse events (SAEs) during 24 weeks of TCZ treatment. Efficacy
      assessments were evaluated as secondary outcomes. Data were analyzed
      descriptively. RESULTS: Overall, 69 patients (7.8%) reported >=1 SAEs. The rate
      of SAEs per 100 person-years was 28.3 (95% confidence interval [95% CI] 23.1
      34.4) overall and was similar across treatment groups: 29.1 (95% CI 21.0-39.2),
      30.3 (95% CI 22.2-40.2), and 20.6 (95% CI 10.3-36.9) in the TCZ 4/8 mg/kg +
      DMARDs, TCZ 8 mg/kg + DMARDs, and TCZ 8 mg/kg monotherapy groups, respectively.
      The most common SAEs were infections (i.e., pneumonia [1.0%] and cellulitis
      [0.9%]). In addition, American College of Rheumatology response rates and
      reductions in mean Disease Activity Score based on a 28-joint count were
      generally similar among treatment groups. CONCLUSION: The safety findings in this
      study were consistent with the previously identified safety profile of TCZ. TCZ
      had an AE profile consistent with prior randomized blinded studies and was
      effective when administered as either monotherapy or in combination with DMARDs
      for the treatment of RA.

PMID- 22972746
TI  - Extracellular matrix proteins secreted from both the endometrium and the embryo
      are required for attachment: a study using a co-culture model of rat blastocysts
      and Ishikawa cells.
AB  - Integrins are expressed in a highly regulated manner at the maternal-fetal
      interface during implantation. However, the significance of extracellular matrix
      (ECM) ligands during the integrin-mediated embryo attachment to the endometrium
      is not fully understood. Thus, the distribution of fibronectin in the rat uterus
      and blastocyst was studied at the time of implantation. Fibronectin was absent in
      the uterine luminal epithelial cells but was intensely expressed in the
      trophoblast cells and the inner cell mass suggesting that fibronectin secreted
      from the blastocyst may be a possible bridging ligand for the integrins expressed
      at the maternal-fetal interface. An Arg-Gly-Asp (RGD) peptide was used to block
      the RGD recognition sites on integrins, and the effect on rat blastocyst
      attachment to Ishikawa cells was examined. There was a significant reduction in
      blastocyst attachment when either the blastocysts or the Ishikawa cells were pre
      incubated with the RGD-blocking peptide. Thus, successful attachment of the
      embryo to the endometrium requires the interaction of integrins on both the
      endometrium and the blastocyst with the RGD sequence of ECM ligands, such as
      fibronectin. Pre-treatment of both blastocysts and Ishikawa cells with the RGD
      peptide also inhibited blastocyst attachment, but not completely, suggesting that
      ECM bridging ligands that do not contain the RGD sequence are also involved in
      embryo attachment.

PMID- 22972747
TI  - Diffeomorphic brain mapping based on T1-weighted images: improvement of
      registration accuracy by multichannel mapping.
AB  - PURPOSE: To improve image registration accuracy in neurodegenerative populations.
      MATERIALS AND METHODS: This study used primary progressive aphasia, aged control,
      and young control T1-weighted images. Mapping to a template image was performed
      using single-channel Large Deformation Diffeomorphic Metric Mapping (LDDMM), a
      dual-channel method with ventricular anatomy in the second channel, and a dual
      channel with appendage method, which utilized a priori knowledge of template
      ventricular anatomy in the deformable atlas. RESULTS: Our results indicated
      substantial improvement in the registration accuracy over single-contrast-based
      brain mapping, mainly in the lateral ventricles and regions surrounding them.
      Dual-channel mapping significantly (P < 0.001) reduced the number of
      misclassified lateral ventricle voxels (based on a manually defined reference)
      over single-channel mapping. The dual-channel (w/appendage) method further
      reduced (P < 0.001) misclassification over the dual-channel method, indicating
      that the appendage provides more accurate anatomical correspondence for
      deformation. CONCLUSION: Brain anatomical mapping by shape normalization is
      widely used for quantitative anatomical analysis. However, in many geriatric and
      neurodegenerative disorders, severe tissue atrophy poses a unique challenge for
      accurate mapping of voxels, especially around the lateral ventricles. In this
      study we demonstrate our ability to improve mapping accuracy by incorporating
      ventricular anatomy in LDDMM and by utilizing a priori knowledge of ventricular
      anatomy in the deformable atlas.

PMID- 22972749
TI  - Domain-domain interactions in full-length p53 and a specific DNA complex probed
      by methyl NMR spectroscopy.
AB  - The tumor suppressor p53 is a homotetramer of 4 * 393 residues. Its core domain
      and tetramerization domain are linked and flanked by intrinsically disordered
      sequences, which hinder its full structural characterization. There is an
      outstanding problem of the state of the tetramerization domain. Structural
      studies on the isolated tetramerization domain show it is in a folded tetrameric
      conformation, but there are conflicting models from electron microscopy of the
      full-length protein, one of which proposes that the domain is not tetramerically
      folded and the tetrameric protein is stabilized by interactions between the N and
      C termini. Here, we present methyl-transverse relaxation optimized NMR
      spectroscopy (methyl-TROSY) investigations on the full-length and separate
      domains of the protein with its methionine residues enriched with (13)C to probe
      its quaternary structure. We obtained high-quality spectra of both the full
      length tetrameric p53 and its DNA complex, observing the environment at 11
      specific methyl sites. The tetramerization domain was as tetramerically folded in
      the full-length constructs as in the isolated domain. The N and C termini were
      intrinsically disordered in both the full-length protein and its complex with a
      20-residue specific DNA sequence. Additionally, we detected in the interface of
      the core (DNA-binding) and N-terminal parts of the protein a slow conformational
      exchange process that was modulated by specific recognition of DNA, indicating
      allosteric processes.

PMID- 22972750
TI  - Arrangement of C60 via the self-assembly of post-functionalizable polyisocyanate
      block copolymer.
AB  - Poly(furfuryl isocyanate) (PFIC), which includes the reactive furan group, was
      synthesized by anionic polymerization using a sodium benzhydroxide (Na-BH), self
      assembly initiator. We determined the optimum polymerization conditions by
      varying both the reaction time and the molar ratio of the monomer to the
      initiator. Block copolymer, poly(furfuryl isocyanate)-b-poly(n-hexyl isocyanate),
      was synthesized under optimized polymerization conditions. The PFIC was modified
      by Diels-Alder reactions with C60 for functionalization. Transmission electron
      microscopy (TEM) was used to study the self-assembly of block copolymers and
      modified block copolymer with C60. C60 formed highly ordered aggregates on the
      PFIC domains via self-assembly of the block copolymer.

PMID- 22972751
TI  - Multiple layers of complexity in cis-regulatory regions of developmental genes.
AB  - Genomes contain the necessary information to ensure that genes are expressed in
      the right place, at the right time, and with the proper rate. Metazoan
      developmental genes often possess long stretches of DNA flanking their coding
      sequences and/or large introns which contain elements that influence gene
      expression. Most of these regulatory elements are relatively small and can be
      studied in isolation. For example, transcriptional enhancers, the elements that
      generate the expression pattern of a gene, have been traditionally studied with
      reporter constructs in transgenic animals. These studies have provided and will
      provide invaluable insights into enhancer evolution and function. However, this
      experimental approach has its limits; often, enhancer elements do not faithfully
      recapitulate native expression patterns. This fact suggests that additional
      information in cis-regulatory regions modulates the activity of enhancers and
      other regulatory elements. Indeed, recent studies have revealed novel functional
      aspects at the level of whole cis-regulatory regions. First, the discovery of
      "shadow enhancers." Second, the ubiquitous interactions between cis-regulatory
      elements. Third, the notion that some cis-regulatory regions may not function in
      a modular manner. Last, the effect of chromatin conformation on cis-regulatory
      activity. In this article, I describe these recent findings and discuss open
      questions in the field.

PMID- 22972752
TI  - Estrogen receptor-alpha is required for the osteogenic response to mechanical
      loading in a ligand-independent manner involving its activation function 1 but
      not 2.
AB  - Estrogen receptor-alpha (ERalpha) is crucial for the adaptive response of bone to
      loading but the role of endogenous estradiol (E2) for this response is unclear.
      To determine in vivo the ligand dependency and relative roles of different
      ERalpha domains for the osteogenic response to mechanical loading, gene-targeted
      mouse models with (1) a complete ERalpha inactivation (ERalpha(-/-) ), (2)
      specific inactivation of activation function 1 (AF-1) in ERalpha (ERalphaAF-1(0)
      ), or (3) specific inactivation of ERalphaAF-2 (ERalphaAF-2(0) ) were subjected
      to axial loading of tibia, in the presence or absence (ovariectomy [ovx]) of
      endogenous E2. Loading increased the cortical bone area in the tibia mainly as a
      result of an increased periosteal bone formation rate (BFR) and this osteogenic
      response was similar in gonadal intact and ovx mice, demonstrating that E2
      (ligand) is not required for this response. Female ERalpha(-/-) mice displayed a
      severely reduced osteogenic response to loading with changes in cortical area (
      78% +/- 15%, p < 0.01) and periosteal BFR (-81% +/- 9%, p < 0.01) being
      significantly lower than in wild-type (WT) mice. ERalphaAF-1(0) mice also
      displayed a reduced response to mechanical loading compared with WT mice
      (cortical area -40% +/- 11%, p < 0.05 and periosteal BFR -41% +/- 8%, p < 0.01),
      whereas the periosteal osteogenic response to loading was unaffected in ERalphaAF
      2(0) mice. Mechanical loading of transgenic estrogen response element (ERE)
      luciferase reporter mice did not increase luciferase expression in cortical bone,
      suggesting that the loading response does not involve classical genomic ERE
      mediated pathways. In conclusion, ERalpha is required for the osteogenic response
      to mechanical loading in a ligand-independent manner involving AF-1 but not AF-2.

PMID- 22972753
TI  - Physical activity monitoring in adolescents with juvenile fibromyalgia: findings
      from a clinical trial of cognitive-behavioral therapy.
AB  - OBJECTIVE: Juvenile fibromyalgia (JFM) is a chronic musculoskeletal pain
      condition that is associated with reduced physical function. Recent research has
      demonstrated that cognitive-behavioral therapy (CBT) is effective in improving
      daily functioning among adolescents with JFM. However, it is not known whether
      these improvements were accompanied by increased physical activity levels. Our
      objective was to analyze secondary data from a randomized clinical trial of CBT
      to examine whether CBT was associated with improvement in objectively measured
      physical activity and whether actigraphy indices corresponded with self-reported
      functioning among adolescents with JFM. METHODS: Participants were 114
      adolescents (ages 11-18 years) recruited from pediatric rheumatology clinics that
      met criteria for JFM and were enrolled in a clinical trial. Subjects were
      randomly (1:1) assigned to receive either CBT or fibromyalgia education (FE).
      Participants wore a hip-mounted accelerometer for 1 week as part of their
      baseline and posttreatment assessments. RESULTS: The final sample included 68
      subjects (94% female, mean age 15.2 years) for whom complete actigraphy data were
      obtained. Actigraphy measures were not found to correspond with self-reported
      improvements in functioning. While self-reported functioning improved in the CBT
      condition compared to FE, no significant changes were seen in either group for
      activity counts, sedentary, moderate, or vigorous activity. The CBT group had
      significantly lower peak and light activity at posttreatment. CONCLUSION:
      Actigraphy monitoring provides a unique source of information about patient
      outcomes. CBT intervention was not associated with increased physical activity in
      adolescents with JFM, indicating that combining CBT with interventions to
      increase physical activity may enhance treatment effects.

PMID- 22972754
TI  - Toward optimal fragment generations for ab initio protein structure assembly.
AB  - Fragment assembly using structural motifs excised from other solved proteins has
      shown to be an efficient method for ab initio protein-structure prediction.
      However, how to construct accurate fragments, how to derive optimal restraints
      from fragments, and what the best fragment length is are the basic issues yet to
      be systematically examined. In this work, we developed a gapless-threading method
      to generate position-specific structure fragments. Distance profiles and torsion
      angle pairs are then derived from the fragments by statistical consistency
      analysis, which achieved comparable accuracy with the machine-learning-based
      methods although the fragments were taken from unrelated proteins. When measured
      by both accuracies of the derived distance profiles and torsion angle pairs, we
      come to a consistent conclusion that the optimal fragment length for structural
      assembly is around 10, and at least 100 fragments at each location are needed to
      achieve optimal structure assembly. The distant profiles and torsion angle pairs
      as derived by the fragments have been successfully used in QUARK for ab initio
      protein structure assembly and are provided by the QUARK online server at
      http://zhanglab.ccmb. med.umich.edu/QUARK/.

PMID- 22972755
TI  - Imaging of soft-tissue tumors.
AB  - The objective of this review is to highlight the major imaging characteristics of
      the main soft-tissue sarcoma histotypes observed in the group "Sarcomi" of the
      Istituto Oncologico Veneto in the last 5 years. A literature review was performed
      using PubMed and textbooks. Radiological imaging can guide the diagnosis for the
      subset of lesions that have typical clinical and imaging features. Soft-tissue
      tumors are common in clinical practice and a systematic clinical and imaging
      approach may guide the diagnosis.

PMID- 22972756
TI  - Extended depth of focus in optical microscopy: assessment of existing methods and
      a new proposal.
AB  - Due to depth of focus constraints, the acquisition of a single 2-D completely in
      focus image of 3-D objects characterized by a relevant depth dimension is not
      possible with a standard light microscope. Since the Seventies numerous methods
      have been proposed to overcome this problem, mainly through different fusion
      processing techniques to extend the microscope's depth of focus. However, given a
      specific application, it is very difficult to know which method yields the best
      results because there are no validated approaches or tested metrics that are
      suitable for real world cases typically lacking in a reference ground truth.
      Although the Universal Quality Index (UQI) is widely used to evaluate output
      quality in image processing, it requires a reference ground truth. Some UQI
      extensions have been proposed to evaluate the output of fusion methods without a
      ground truth, but sufficient analyses have not been carried out to confirm their
      equivalence to the standard UQI in terms of (evaluation) performance. We propose
      a new method to extend the microscope's depth of focus and, using synthetic
      stacks of images with ground truth attached, show that it is superior to state-of
      the-art methods. We also demonstrate that the output of metrics proposed as UQI
      extensions is different from that of the UQI. Finally, we validate a new approach
      to evaluate extended depth of focus methods using real world stacks of slices, as
      per the UQI, but without the need for a reference ground truth.

PMID- 22972757
TI  - Transoral en bloc resection of superficial laryngeal and pharyngeal cancers.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and safety
      of minimally invasive transoral en bloc resection of superficial pharyngeal and
      laryngeal cancers. METHODS: Forty-one superficial lesions (from 35 patients) were
      resected transorally under a surgical microscope using a monopolar cautery.
      Quality of life (QOL) was assessed using a questionnaire European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck
      Cancer Module (EORTC QLQ-H&N35) 1 year after the surgery. RESULTS: Twenty-eight
      hypopharyngeal, 5 oropharyngeal, and 8 laryngeal cancers were operated on using
      this method. The surgical field was widely exposed with a wide-caliber scope or
      extending laryngoscope. A bimanual procedure under a surgical microscope enabled
      us to achieve en bloc resection. The local control rate was 98%. No postoperative
      dyspnea or dysphagia was observed. Postoperative QOL scores were favorable.
      CONCLUSIONS: Our transoral en bloc resection technique can be easily adopted, and
      it effectively maintained QOL after treatment.

PMID- 22972758
TI  - Study of the catechol-o-methyltransferase (COMT) gene with high aggression in
      children.
AB  - The etiology of childhood-onset aggression (COA) is poorly understood, but early
      COA can be considered as a strong risk factor for adult delinquency and criminal
      behavior. Callous-unemotional (CU) traits have been proposed as a developmental
      model of antisocial behavior. Catechol O-methyltransferase (COMT) has been
      associated with aggression, attention deficit/hyperactivity disorder (ADHD), and
      other psychiatric disorders. We report an association study between COMT single
      nucleotide polymorphisms (SNPs), childhood aggression, and the CU trait in our
      sample of 144 children with scores at or exceeding the 90th percentile on the
      aggression subscale of the parent-reported Child Behavior Checklist and the
      Teacher's Report Form. The genotype analysis of rs6269 showed nominally
      significant association (P = .019) and rs4818 showed a trend (P = .064) with COA.
      Trends were observed for rs6269 and rs4818 with CU scores (P < .10) as well. The
      analyses stratified by ADHD, or gender showed no significant results. This is the
      first report to our knowledge evaluating COMT SNPs with the phenotype of high
      aggression in children with a possible role for the COMT marker in CU traits.
      Given the importance of CU traits in antisocial behavior, further investigation
      of COMT is warranted.

PMID- 22972759
TI  - Pain intensity variability and its relationship with quality of life in youths
      with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To describe variability of pain intensity experienced by youths with
      juvenile idiopathic arthritis (JIA) and examine factors related to within-day
      patterns of pain and the relationship between magnitude of pain variability and
      quality of life. METHODS: Pain intensity was self-reported on a visual analog
      scale (VAS; range 0-100) by 112 youths with JIA ages 8-18 years using electronic
      diaries 3 times per day for 7 days. Average absolute change in pain (AAC) was
      computed as a measure of the magnitude of pain variability for each participant.
      Logistic regression was used to examine the relationship between demographic and
      disease characteristics and the probability of having high pain variability (AAC
      >=10 VAS units). Linear regression was used to examine the relationship between
      quality of life (assessed by the Pediatric Quality of Life Inventory) and AAC.
      The generalized estimating equations approach was used to examine the
      relationship between the time of day and pain intensity. RESULTS: The mean +/- SD
      AAC was 15.6 +/- 10.5. The majority of youths (65%) had high AAC (>=10 VAS
      units). Disease severity predicted high pain variability (beta = 0.02, P =
      0.044). Higher AAC predicted lower quality of life (adjusted R(2) = 0.194, beta =
      -0.59, P = 0.003). Within-day patterns of pain intensity varied by JIA subtype
      and sex. CONCLUSION: This study characterized the pain intensity variability
      experienced by youths with JIA. Pain variability throughout the day was common,
      varied by JIA subtype and sex, and was related to quality of life. These findings
      have implications for future pain research, patient education, and development of
      clinical interventions for this population.

PMID- 22972760
TI  - Seizure freedom is not adversely affected by early discontinuation of concomitant
      anti-epileptic drugs in the EULEV cohort of levetiracetam users.
AB  - PURPOSE: Fear of discontinuing concomitant anti-epileptic drugs (AEDs) may lead
      to potentially unnecessary and perhaps unsafe polypharmacy. The effect of
      withdrawing concomitant AEDs on epilepsy control was therefore studied in long
      term users of levetiracetam. METHODS: The EULEV cohort followed patients
      initiating levetiracetam in France in 2005 or 2006 for one year. In those
      maintaining levetiracetam throughout the study period, the association of a
      reduction in the number of concomitant AEDs during the first six months with
      seizure-freedom during the last six months of follow-up was investigated using
      logistic regression. RESULTS: Of the 356 patients continuing levetiracetam for at
      least 1 year, 140 (39.3%) were seizure-free during the last six months of follow
      up. Partial symptomatic or generalised idiopathic epilepsy were associated with
      greater seizure-freedom than partial cryptogenic disease. Factors associated with
      seizures were: longer disease duration, initial incapacity, increased number of
      seizures in the six months preceding levetiracetam initiation, and number of
      consultations for epilepsy in the six months preceding levetiracetam initiation.
      There was a trend for the association between the early reduction in the number
      of concomitant AEDs and seizure-free status later during follow-up, which however
      did not reach statistical significance in the final propensity score-adjusted
      multivariate model (OR = 1.8, 95%CI [0.8;4.0]). CONCLUSIONS: Taking into account
      the various risk factors for seizures, the early reduction of concomitant AEDs
      was not associated with worse seizure rates during follow-up in real-life users
      of levetiracetam.

PMID- 22972761
TI  - AFM characterization of biomolecules in physiological environment by an advanced
      nanofabricated probe.
AB  - Many relevant questions in biology and medicine require both topography and
      chemical information with high spatial resolution. Several biological events that
      occur at the nanometer scale level need to be investigated in physiological
      conditions. In this regard Atomic Force Microscopy (AFM) is one of the most
      powerful tools for label-free nanoscale characterization of biological samples in
      liquid environment. Recently, the coupling of Raman spectroscopy to scanning
      probe microscopies has opened new perspectives on this subject; however, the
      coupling of quality AFM spectroscopy with Raman spectroscopy in the same probe is
      not trivial. In this work we report about the AFM capabilities of an advanced
      high-resolution probe that has been previously nanofabricated by our group for
      coupling with Raman spectroscopy applications. We investigate its use for liquid
      AFM measurements on biological model samples like lipid bilayers, amyloid
      fibrils, and titin proteins. We demonstrate topography resolution down to
      nanometer level, force measurement and stable imaging capability. We also discuss
      about its potential as nanoscale chemical probe in liquid phase.

PMID- 22972762
TI  - A critical evaluation of the tumor-targeting properties of bispecific antibodies
      based on quantitative biodistribution data.
AB  - Bispecific and bifunctional antibodies are attracting considerable interest as
      innovative anti-cancer therapeutics, but their ability to selectively localize at
      the tumor site has rarely been studied by quantitative biodistribution studies in
      immunocompetent animal models or in patients. Here, we describe the production of
      a novel bifunctional antibody, consisting of the F8 antibody (specific to the
      alternatively spliced EDA domain of fibronectin) fused to the extracellular
      portion of CD86 (co-stimulatory molecule B7.2). However, the fusion molecule was
      unable to target tumors in vivo. These data suggest that bispecific antibodies do
      not always localize on tumors and should therefore be characterized by imaging or
      biodistribution studies.

PMID- 22972763
TI  - Transplantation of a hydrogen bonding network from West Nile virus protease onto
      Dengue-2 protease improves catalytic efficiency and sheds light on substrate
      specificity.
AB  - The two-component serine protease of flaviviruses such as Dengue virus (DENV) and
      West Nile virus (WNV) are attractive targets for inhibitor/therapeutic design.
      Peptide aldehyde inhibitors that bind to the covalently tethered two-component
      WNV protease (WNVpro) with 50% inhibitory concentration (IC(50)) at sub
      micromolar concentrations, bind the equivalent DENV-2 protease (DEN2pro) with
      IC(50) of micromolar concentrations at best. Conversely, the protease inhibitor
      aprotinin binds DEN2pro ~1000-fold more tightly than WNVpro. To investigate the
      residues that are crucial for binding specificity differences, a binding-site
      network of hydrogen bonds was transplanted from WNVpro onto DEN2pro. The
      transplantations were a combination of single, double and triple mutations
      involving S79D, S83N and S85Q. The mutant DENV proteases, except those involving
      S85Q, proved to be more efficient enzymes, as measured by their kinetic
      parameters. The binding affinities of the mutants to peptide inhibitors however
      showed only marginal improvement. Protein structure modeling suggests that the
      negatively charged residue cluster, Glu89-Glu92, of the NS2B cofactor may play an
      important role in determining substrate/inhibitor-binding specificity. These same
      residues may also explain why aprotinin binds more tightly to DEN2pro than
      WNVpro. Our results suggest that structure-based inhibitor design experiments
      need to explicitly consider/include this C-terminal region whose negative charge
      is conserved across the four DENV serotypes and also among the flavivirus family
      of proteases.

PMID- 22972764
TI  - Risk factors for progression in hand osteoarthritis: a systematic review.
AB  - OBJECTIVE: To assess the risk factors for progression of hand osteoarthritis
      (OA). METHODS: In a systematic review of cohort studies, medical literature
      databases were searched up to May 2012 for articles reporting data on the
      association between risk factors and hand OA progression. The quality of these
      studies was assessed by 2 independent reviewers using a criteria scoring system
      of 16 items, and studies were dichotomized into those with scores of 69% or over
      and those with scores under 69%. Best evidence synthesis was used to determine
      the level of evidence per risk factor. RESULTS: In total, 14 articles that
      fulfilled the selection criteria were included, of which 8 were high quality. The
      most frequently investigated risk factors were age, sex, radiographic features
      (e.g., erosive OA), and scintigraphy. Progression was mostly defined by
      radiographic criteria, but also clinical progression as an outcome was described.
      Most of the investigated risk factors showed limited or inconclusive evidence for
      an association with hand OA progression. Limited evidence according to the best
      evidence synthesis with most available studies was present for the association
      between a positive scintigraphic scan and radiographic progression (up to 2.8
      times more progression than negative joints). CONCLUSION: Limited evidence is
      available for a positive association between an abnormal scintigraphic scan and
      radiographic hand OA progression. These data suggest that a positive
      scintigraphic scan as an inclusion criterion for studies that aim to show
      structural modification can increase the power of such studies. Future
      longitudinal studies with a well-defined baseline population are needed to search
      for risk factors of hand OA progression.

PMID- 22972765
TI  - Psychological morbidity, burden, and the mediating effect of social support in
      adult children caregivers of oncological patients undergoing chemotherapy.
AB  - OBJECTIVES: This study examines the association between psychological morbidity,
      social support, and demographic and clinical variables in adult children of
      cancer patients undergoing chemotherapy. Special attention was given to the
      variable level of parental dependency. The main predictors of caregiving burden
      were tested, as well as the mediating role of social support in the relationship
      between psychological morbidity and burden. METHODS: A total of 214 adult
      children caregivers of parents with cancer were recruited in Northern Portugal
      central hospitals. Caregivers completed Portuguese versions of the Depression
      Anxiety and Stress Scales, Impact of Event Scale-Revised, Satisfaction with
      Social Support Scale, and Burden Assessment Scale. RESULTS: Significant
      associations among psychological, demographic, and clinical variables were found.
      Adult children with a greater perception of parent's dependency showed more
      distress, higher posttraumatic stress disorder (PTSD) symptoms, greater
      caregiving burden, and less satisfaction with social support. Hierarchical
      regression analyses revealed the main predictors of caregiver burden to be as
      follows: being a woman, caregiving duration, having a dependent parent, more
      distress and PTSD symptoms, and poorer social support. Social support was found
      to be a partial mediator in the relationship between psychological morbidity and
      caregiver burden. CONCLUSIONS: Results underscore the importance of perceived
      parental dependency in offspring's caregivers. Findings support the
      multidimensional issues associated to burden in this specific population,
      stressing satisfaction with social support as an important mediator between
      distress/PTSD and burden. Implications for further research as well as
      limitations of the present study are discussed. Psychosocial interventions should
      focus on caregivers' social resources to facilitate psychological well-being.

PMID- 22972766
TI  - Morphoanatomical and phytochemical studies of Salvia lachnostachys (Lamiaceae).
AB  - Salvia lachnostachys Benth., Lamiaceae, is a endemic species from southern
      Brazil. The essential oil of its leaves and flowers is mainly constituted by
      aliphatic compounds, such as dodecanoic acid, with sesquiterpenes as minor
      constituents. This work evaluated the morphology, anatomy, microchemistry, and
      phytochemistry of S. lachnostachys to provide advanced knowledge of Brazilian
      plants with medicinal potential. Light and scanning electron microscopy
      techniques were used in the anatomical and microchemical studies. Compounds were
      isolated by chromatographic techniques, identified by analysis of their NMR
      spectra and compared with published data. S. lachnostachys can be distinguished
      from other related species mainly by its petiolate leaves, terminal
      inflorescence, persistent bracts, and villous-glandular corolla. The stem and
      leaves of S. lachnostachys display anatomical characteristics common to the
      family Lamiaceae. However, this species can be distinguished from other family
      members by the morphology and the presence of eglandular and glandular trichomes,
      as well as the organization of the vascular bundles of the petiole. The
      phytochemical results revealed that S. lacnostachys produces oleanolic and
      ursolic acids in addition to the diterpene fruticuline A, which is a rare
      compound, previously found only in Salvia fruticulosa Benth. and S. corrugata
      Vahl. Ursolic and oleanolic acids are bioactive triterpenes that exhibit
      antiatherosclerotic, anticancer, antihypertensive, antinflammatory, antileukemic,
      antimutagenic, antioxidant, antiproliferative, and antiviral activities, and
      fruticuline A has antibacterial activity.

PMID- 22972767
TI  - First anxiety, afterwards depression: psychological distress in cancer patients
      at diagnosis and after medical treatment.
AB  - OBJECTIVE: The purpose of this study was to assess psychosocial changes at two
      particular moments: at cancer diagnosis and 2-4 weeks after having finished
      treatment. MATERIAL AND METHODS: A total of 67 cancer outpatients were assessed
      in this study. The inclusion/exclusion criteria were as follows: ambulatory
      cancer patients aged 18 years or older and receiving medical treatment. Patients
      with a performance status <50 or with cognitive impairment (>=3 errors in the
      Pfeiffer Questionnaire) were excluded. The inclusion period ranged from 1 April
      2005 to 30 April 2007. The scales used were the 14-item Hospital Anxiety and
      Depression Scale (HADS), which has two subscales for anxiety (seven items) and
      for depression (seven items), the Quality of Life Short Form 36 Questionnaire,
      the Mental Adjustment Scale and the Medical Outcomes Study Questionnaire for
      measuring social support. All data were compared with sociodemographic and
      medical characteristics. RESULTS: Patients had higher levels of pre-treatment
      versus post-treatment anxiety (HADS-Anxiety mean, 7.41 versus 6.69), whereas
      depression scores were higher post-treatment versus pre-treatment (HADS
      Depression mean, 3.14 versus 3.89). After medical treatment, patients were more
      fatigued, with lower performance status (Karnofsky Index), less social support
      and less quality of life, but no differences in coping styles were found. Women
      had higher levels of anxiety than men. Patients with psychiatric antecedents had
      higher levels of distress, but these differences were only observed after
      diagnosis and not after the treatment. In general, head and neck cancer patients
      had higher levels of distress, worse coping and worse social functioning.
      CONCLUSIONS: Cancer patients require special consideration before and after
      treatment. Anxiety is the symptom that characterizes diagnosis, whereas
      depression is more common after medical treatment. The head and neck cancer
      patients were the group with the highest complexity.

PMID- 22972768
TI  - Foot and ankle kinematics in rheumatoid arthritis: influence of foot and ankle
      joint and leg tendon pathologies.
AB  - OBJECTIVE: From early onset of the disease, patients with rheumatoid arthritis
      (RA) experience walking impairments. Pathologic effects of RA on foot and ankle
      structures have been studied clinically, but little is known as to how they
      relate to kinematic changes during gait. The aim of this study was to explore the
      relationship between clinically observed pathologies of foot and ankle joints and
      leg tendons and the corresponding gait kinematics. METHODS: The gait of 25
      subjects with varying stages of RA was recorded and foot and ankle kinematics
      were assessed. Magnetic resonance imaging was performed for each subject: first
      metatarsophalangeal (MTP) joint, midfoot, and hindfoot synovitis, erosion scores,
      and leg tendon involvement were determined. The joint alignment and motion score
      represented daily clinical assessment. The 95% confidence intervals of the
      Spearman's correlation coefficient tests were used to explore the relationships
      between the clinical and kinematic parameters. RESULTS: Maximum first MTP joint
      dorsiflexion at preswing was related to reduced first MTP joint passive motion,
      first MTP joint synovitis and erosion, midfoot synovitis and erosion, and
      hindfoot erosion. Midfoot pronation range of motion during single stance was
      related to subtalar alignment and Achilles tendon involvement. Hindfoot eversion
      range of motion during single stance was related to subtalar alignment and
      peroneus longus tendon involvement. Involvement of the tibialis posterior tendon
      could not be identified as an independent factor influencing foot or ankle
      kinematics. CONCLUSION: Our findings suggest moderate to strong relationships
      between foot and ankle gait kinematics and structural pathologies.

PMID- 22972769
TI  - Pax2 modulates proliferation during specification of the otic and epibranchial
      placodes.
AB  - BACKGROUND: The inner ear and epibranchial ganglia of vertebrates arise from a
      shared progenitor domain that is induced by FGF signalling, the posterior
      placodal area (PPA), before being segregated by Wnt signalling. One of the first
      genes activated in the PPA is the transcription factor Pax2. Loss-of- and gain-of
      function studies have defined a role for Pax2 in placodal morphogenesis and later
      inner ear development, but have not addressed the role Pax2 plays during the
      formation and maintenance of the PPA. RESULTS: To understand the role of Pax2
      during the development of the PPA, we used over-expression and repression of
      Pax2. Both gave rise to a smaller otocyst and repressed the formation of
      epibranchial placodes. In addition, cell cycle analysis revealed that Pax2
      suppression reduced proliferation of the PPA. CONCLUSIONS: Our results suggest
      that Pax2 functions in the maintenance but not the induction of the PPA. One role
      of Pax2 is to maintain proper cell cycle proliferation in the PPA.

PMID- 22972770
TI  - Action of andiroba oil (Carapa guianensis) on Rhipicephalus sanguineus
      (Latreille, 1806) (Acari: Ixodidae) semi-engorged females: morphophysiological
      evaluation of reproductive system.
AB  - Because of the increasing medical-veterinary importance of ticks, the development
      of alternative control methods, less aggressive to the host and the environment
      has become the target of several researches. In this sense, the present study
      analyzed the action of different concentrations (5, 10, and 20%) of andiroba seed
      oil (Carapa guianensis) on the reproductive system of Rhipicephalus sanguineus
      females, through histochemical techniques and the quantification of the
      reproductive efficiency index. The results showed that andiroba oil is a potent
      natural agent, able to cause several changes in the oocytes of this species,
      impairing the reproductive success, once this natural product induces great
      physiological changes in the oocytes in all development stages, such as drastic
      reduction in proteins, polysaccharides, and lipids in these cells, and these
      components are essential for the viability of the embryo. In addition, it was
      observed that this product stimulate the oviposition, mainly at the concentration
      of 20%. This higher production of eggs represents a defense mechanism developed
      by the organism in order to ensure the reproductive success of the species, even
      in the presence of the toxic agent. However, the results obtained suggested that
      the laid eggs would not be viable, due to the great changes undergone by the
      oocytes. Thus, the present study showed that the use of this vegetal product
      would be an alternative way to control the ticks, bringing benefits similar to
      the ones obtained through the use of synthetic acaricides; however, with less
      damage to nontarget organisms and the environment as well.

PMID- 22972771
TI  - Effects of self-directed stress management training and home-based exercise on
      stress management skills in cancer patients receiving chemotherapy.
AB  - Although exercise may be used by some to decrease distress, little is known about
      how it may contribute to stress management (SM) among patients receiving
      chemotherapy. We evaluated whether exercise separately or in combination with SM
      training is effective at increasing perceived ability to manage stress. Patients
      receiving chemotherapy (N = 391) were randomized to receive usual care only
      (UCO), SM, exercise (EX), or stress management and exercise (SMEX). They
      completed the Measure of Current Status prior to receiving chemotherapy and 12
      weeks after the first infusion. We hypothesized that participants randomized to
      an intervention condition would report improvements in relaxation, awareness of
      tension, getting needs met and coping confidence compared with those receiving
      UCO. Results indicated significant group-by-time interactions for the following:
      relaxation (UCO versus SM, p = 0.008), awareness of tension (UCO versus SMEX, p =
      0.029 and UCO versus EX, p < 0.001), getting needs met (UCO versus SMEX, p =
      0.020) and Measure of Current Status total score (UCO versus SMEX, p = 0.007 and
      UCO versus EX, p = 0.016). There were no group-by-time interactions for coping
      confidence (p-values >0.05). This study provides support for including an
      exercise component in SM interventions for cancer patients receiving chemotherapy
      (clinicaltrials.gov identifier: NCT00740038).

PMID- 22972772
TI  - Impact of musculoskeletal ultrasound in an outpatient rheumatology clinic.
AB  - OBJECTIVE: To evaluate the impact of musculoskeletal ultrasound (MSUS) as a
      complementary method to clinical assessment on rapid diagnosis and therapeutic
      decisions in a busy outpatient rheumatology clinic. METHODS: Sixty patients with
      different musculoskeletal symptoms were included in the study. Three expert
      rheumatologists performed the clinical examination and filled out a standardized
      clinical report sheet with the following parameters: general and/or local
      diagnoses, planned systemic and/or local treatment, and their decision concerning
      the use of MSUS evaluation complementary to clinical examination. Another
      rheumatologist, blinded to clinical data, performed the MSUS assessment of the
      anatomic areas selected by the clinicians. The impact of the new information
      obtained by MSUS on the initial diagnosis and therapeutic strategy was estimated
      by the degree of change in the initial clinical diagnosis and therapy decisions.
      RESULTS: Of 60 patients (67 anatomic areas), MSUS was considered as necessary
      after clinical examination in 39 patients (65%), totaling 43 anatomic areas
      (64.17%). An overall change of the initial clinical diagnosis was present in 60%
      of the anatomic areas (P = 0.0175). In all of the anatomic areas (100%), the new
      diagnosis was more objective and detailed. An overall change of the initial
      systemic therapy was present in 25% of anatomic areas (P = 0.0014) and in 36% of
      anatomic areas (P = 0.095) for local therapy. A guided diagnostic aspiration was
      decided to be performed in 15% of anatomic areas and a guided therapeutic
      injection in 22% of anatomic areas. CONCLUSION: Enhanced information obtained by
      MSUS evaluation leads to changes, with a significant impact on the initial
      diagnosis and treatment strategy designed after clinical examination.

PMID- 22972773
TI  - Epimerization in peptide thioester condensation.
AB  - Peptide segment couplings are now widely utilized in protein chemical synthesis.
      One of the key structures for the strategy is the peptide thioester. Peptide
      thioester condensation, in which a C-terminal peptide thioester is selectively
      activated by silver ions then condensed with an amino component, is a powerful
      tool. But the amino acid adjacent to the thioester is at risk of epimerization.
      During the preparation of peptide thioesters by the Boc solid-phase method, no
      substantial epimerization of the C-terminal amino acid was detected.
      Epimerization was, however, observed during a thioester-thiol exchange reaction
      and segment condensation in DMSO in the presence of a base. In contrast,
      thioester-thiol exchange reactions in aqueous solutions gave no epimerization.
      The epimerization during segment condensation was significantly suppressed with a
      less polar solvent that is applicable to segments in thioester peptide
      condensation. These results were applied to a longer peptide thioester
      condensation. The epimer content of the coupling product of 89 residues was
      reduced from 27% to 6% in a condensation between segments of 45 and 44 residues
      for the thioester and the amino component, respectively.

PMID- 22972776
TI  - Rapid and facile detection of four date rape drugs in different beverages
      utilizing proton transfer reaction mass spectrometry (PTR-MS).
AB  - In this work, we illustrate the application of proton transfer reaction mass
      spectrometry (PTR-MS) in the field of food and drink safety. We present proof-of
      principle measurements of four different drinks (water, tea, red wine and white
      wine) each spiked separately with four different date rape drugs (chloral
      hydrate, tricholorethanol, gamma-butyrolactone and butanediol). At first, the
      ideal PTR-MS operating conditions (reduced electric field strength and monitoring
      the most abundant [fragment] ion) for detection of the drugs were determined
      utilizing a time-of-flight-based PTR-MS instrument. We then dissolved small
      quantities of the drugs (below the activation threshold for effects on humans)
      into the various types of drinks and detected them using a quadrupole-based PTR
      MS instrument via two different sampling methods: (1) dynamic headspace sampling
      and (2) direct liquid injection. Both methods have their advantages and
      drawbacks. Only with dynamic headspace sampling can rape drug contaminations be
      detected within a timeframe of seconds, and therefore, this method is the most
      promising use of PTR-MS as a fast, sensitive and selective monitor for the
      detection of food and drink contamination.

PMID- 22972774
TI  - Association of copper-zinc superoxide dismutase (SOD1) and manganese superoxide
      dismutase (SOD2) genes with nonsyndromic myelomeningocele.
AB  - BACKGROUND: A common and severe neural tube defect (NTD) phenotype,
      myelomeningocele (MM), results from the defective closure of the caudal end of
      the neural tube with herniation of the spinal cord and meninges through the
      vertebral column. The exact mechanisms for NTDs are unknown, but excessive
      oxidative stress, particularly in association with maternal diabetes, has been
      postulated as a mechanism for MM. METHODS: The SNPlex Genotyping (ABI, Foster
      City, CA) platform was used to investigate single nucleotide polymorphisms (SNPs)
      across the superoxide dismutase (SOD) 1 and 2 genes to assess their association
      with MM risk. The study population included 329 trio (affected child and both
      parents) and 281 duo (affected child and one parent) families. Only cases with
      documented MM were studied. Seventeen SNPs across the SOD1 and SOD2 genes met the
      quality-control criteria to be considered for statistical analysis. Genetic
      association was assessed using the family-based transmission disequilibrium test
      in PLINK (a genome association analysis toolset). RESULTS: Four SNPs in the SOD1
      gene (rs 202446, rs202447, rs4816405, and rs2070424) and one SNP in the SOD2 gene
      ( rs5746105) [corrected] appeared to be associated with MM risk in our
      population. After adjusting for multiple testing, these SNPs remained
      significant. CONCLUSION: This study provides the first genetic evidence to
      support association of myelomeningocele with superoxide scavenging. The rare
      alleles of the five specific SNPs within SOD1 and SOD2 appear to confer a
      protective effect on the susceptibility for MM risk in the MM population tested.
      Further evaluation of the roles of superoxide scavenging and neural tube
      development is warranted.

PMID- 22972777
TI  - Analysis of breath by proton transfer reaction time of flight mass spectrometry
      in rats with steatohepatitis induced by high-fat diet.
AB  - Breath testing has been largely used as a diagnostic tool, but the difficulties
      in data interpretation and sample collection have limited its application. We
      developed a fast (< 20 s), on-line, non-invasive method for the collection and
      analysis of exhaled breath in awake rats based on proton transfer reaction time
      of flight mass spectrometry (PTR-ToF-MS) and applied it to investigate possible
      relationships between pathologies induced by dietary regime and breath
      composition. As a case study, we investigated rats with dietary induced non
      alcoholic steatohepatitis (NASH) and modifications induced by coffee addition to
      the diet. We considered two different diets (standard and high fat) complemented
      with two different drinking possibilities (water or decaffeinated coffee) for a
      total of four groups with four rats each. Several spectrometric peaks were
      reliable markers for both dietary fat content and coffee supplementation. The
      high resolution and accuracy of PTR-ToF-MS allowed the identification of related
      compounds such as methanol, dimethyl sulphide, dimethyl sulphone and ammonia. In
      conclusion, the rapid and minimally invasive breath analysis of awake rats
      permitted the identification of markers related to diet and specific pathologic
      conditions and provided a useful tool for broader metabolic investigations.

PMID- 22972778
TI  - Free and bound aroma compounds characterization by GC-MS of Negroamaro wine as
      affected by soil management.
AB  - Negroamaro is an autochthonous wine grape variety of Southern Italy, which is
      becoming very important for the Italian wine market. The wine aroma is primary
      affected by the chemical composition of grapes, which can be influenced also by
      agronomic practices such as soil management. In this study, the free and bound
      aroma characterization was performed by gas chromatography-mass spectrometry
      analyses, and the influence of two soil managements (cover cropping and soil
      tillage) was evaluated. A total of 40 volatile compounds were observed in the
      wine samples. Alcohols (55.7 mg/L), fatty acids (7.0 mg/L) and esters (6.6 mg/L)
      were found as the main classes in Negroamaro wine. The results showed that the
      aroma composition of Negroamaro wine was positively affected by soil tillage
      probably because of the higher water stress (psi(s)) recorded in the vines from
      this treatment. Indeed, among the free volatile compounds, higher contents of
      esters, carboxylic acids, alcohols, phenolics and acetamides together with lower
      contents of sulfurs compounds were found in soil tillage wine. Conversely, no
      difference was observed in glycoside volatile compounds.

PMID- 22972779
TI  - Seed oil triglyceride profiling of thirty-two hybrid grape varieties.
AB  - Triglyceride profile of seed oil samples from 32 hybrid grape varieties not
      studied before was investigated. A new method for the analysis of
      triacylglycerols (TAGs) has been developed based on the direct infusion in the
      electrospray ionization (ESI) source and employing tetrahydrofuran/methanol/water
      (85:10:5 v|v|v) as solvent; the formation of [M + Na](+) ions in high yield has
      been observed. TAGs were identified by ESI-tandem mass spectrometry analysis, and
      the matrix-assisted-laser-desorption-ionization and time-of-flight profile of
      samples was determined. Six were the principal TAGs identified in seed oil:
      trilinolein (LLL) was the most abundant (43%), followed by dilinoleoyl
      oleoylglycerol (LOL, 23%), and dilinoleoyl-palmitoylglycerol (LPL, 15%).
      Compounds present in lower concentration were LSL and LOO (11%), LOP (6%), and
      LSP (2%). Compared with seed oils produced from V. Vinifera grapes, some
      significant differences in the relative abundances of TAGs were found, in
      particular hybrid grape seed oils showed higher LOL and lower LPL content,
      respectively. Among the samples studied, a particularly high content of LLL (rich
      in unsaturated fatty acids) was found in seed oils from two red varieties.

PMID- 22972780
TI  - Effect of sugars on liquid-vapour partition of volatile compounds in ready-to
      drink coffee beverages.
AB  - The effect of sugars (sucrose, lactose, glucose, fructose, 10%w/v) on the liquid
      vapour partition of selected volatile compounds of coffee beverages has been
      investigated in espresso coffee and ready-to-drink (RTD) canned coffee prepared
      and obtained by using the same Arabica roasted coffee beans blend. Aroma
      composition of coffee beverages has been preliminary investigated by headspace
      gas chromatography (HS-GC) and solid phase microextraction-HS-GC-mass
      spectrometry to characterize the volatile pattern of the systems and to evaluate
      the effects of sugars on the aroma release/retention. Then, the liquid-vapour
      partition coefficient (k) of 4 selected key aroma compounds (diacetyl, 2,3
      pentanedione, ethylpyrazine, hexanal) was determined in water, sugars solutions
      as well as RTD coffee brews added with the same sugars (10%w/v). Sugars added in
      coffee beverages affected the release of the volatiles and thus its aroma profile
      with differences due to the type of added sugar and coffee brew type. The k
      values of the selected volatile compounds resulted different depending on the
      model system composition (water, coffee brew) and sugar type added. In
      particular, melanoidins as well as other non-volatile components (lipids, acids,
      carbohydrates) in the RTD coffee brews could be implied in the change of k of the
      volatile compounds in respect to that observed in water. The effects of the sugar
      type on the release/retention of the four key coffee aroma compounds were partly
      explained in terms of 'salting out' especially for the more polar volatile
      compounds and in the sucrose-added model systems. The change of chemical and
      physico-chemical properties of the water and brews induced by the sugars as well
      as the occurrence of interactions between volatile compounds and non-volatile
      components may be implied in the reduction of the vapour partition of the aroma
      compounds.

PMID- 22972781
TI  - Using elemental profiles and stable isotopes to trace the origin of green coffee
      beans on the global market.
AB  - A broad elemental profile incorporating 54 elements (Li, Be, B, Na, Mg, Al, P, K,
      Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Mo, Pd, Ag, Cd,
      Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Er, Tm, Yb, Re, Ir, Pt, Au,
      Hg, Tl, Pb, Bi and U) in combination with delta(2) H, delta(13) C, delta(15) N
      and delta(18) O was used to characterise the composition of 62 green arabica
      (Coffea arabica) and robusta (Coffea canephora) coffee beans grown in South and
      Central America, Africa and Asia, the four most internationally renowned areas of
      production. The delta(2) H, Mg, Fe, Co and Ni content made it possible to
      correctly assign 95% of green coffee beans to the appropriate variety. Canonical
      discriminant analysis, performed using delta(13) C, delta(15) N, delta(18) O, Li,
      Mg, P, K, Mn, Co, Cu, Se, Y, Mo, Cd, La and Ce correctly traced the origin of 98%
      of coffee beans.

PMID- 22972782
TI  - Detection of sheep and goat milk adulterations by direct MALDI-TOF MS analysis of
      milk tryptic digests.
AB  - In dairy field, one of the most common frauds is the adulteration of higher value
      types of milk (sheep's and goat's) with milk of lower value (cow's milk). This
      illegal practice has an economic advantage for milk producers and poses a threat
      for consumers' health because of the presence of hidden allergens as, for
      example, cow milk proteins, in particular, alpha(s1)-casein and beta
      lactoglobulin. The urgent need of sensitive techniques to detect this kind of
      fraud brought to the development of chromatographic, immunoenzymatic,
      electrophoretic and mass spectrometric assays. In the current work, we present a
      fast, reproducible and sensitive method based on the direct matrix-assisted laser
      desorption/ionization-time-of-flight (MALDI-TOF) MS analysis of milk tryptic
      digests for the detection of milk adulteration by evaluating specie-specific
      markers in the peptide profiles. Several pure raw and commercial milk samples and
      binary mixtures containing cows' and goats', cows' and sheep's and goats' and
      sheep's milk (concentrations of each milk varied from 0% to 100%) were prepared,
      and tryptic digests were analyzed by MALDI-TOF MS. The use of the new MALDI
      matrix alpha-cyano-4-chlorocinnamic acid allowed to detect cow and goat milk
      peptide markers up to 5% level of adulteration. Finally, from preliminary data,
      it seems that the strategy could be successfully applied also to detect similar
      adulterations in cheese samples.

PMID- 22972783
TI  - MS-based characterization of alpha(s2)-casein isoforms in donkey's milk.
AB  - The primary structure of four alpha(s2)-casein (CN) isoforms, present as minor
      components in the dephosphorylated CN fraction of a milk sample collected in
      Eastern Sicily from an individual donkey belonging to the Ragusano breed at
      middle lactation stage, was determined, using the known donkey's alpha(s2)-CN
      (GenBank Acc. No. CAV00691; M(r) 26,028 Da) as reference. Proteins, with
      experimentally measured M(r) of 25,429, 21,939, 25,203 and 21,713 Da, were
      isolated by the combined use of reversed-phase high-performance liquid
      chromatography (RP-HPLC) and two-dimensional polyacrylamide gel electrophoresis.
      The major spot of each gel, corresponding to a single protein, was digested by
      trypsin, alpha-chymotrypsin and endoproteinase Glu-C. The resulting peptide
      mixtures were analyzed by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry and capillary RP-HPLC/nano-electrospray ionization
      tandem mass spectrometry, and the data obtained were used for the sequence
      determination. The isoforms are produced from differential splicing events
      involving exons 4, 5 and 6 and parts of the exon 17.

PMID- 22972784
TI  - Identification of glucosinolates in capers by LC-ESI-hybrid linear ion trap with
      Fourier transform ion cyclotron resonance mass spectrometry (LC-ESI-LTQ-FTICR MS)
      and infrared multiphoton dissociation.
AB  - An liquid chromatography-mass spectrometry method using electrospray ionization
      in negative ion mode coupled with a hybrid quadrupole linear ion trap and Fourier
      transform ion cyclotron resonance (FTICR) mass spectrometer was applied to
      characterize of intact glucosinolates (GLSs) in crude sample extracts of wild bud
      flowers of Capparis spinosa (Capparis species, family Capparaceae). Structural
      information of GLSs was obtained upon precursor ions' isolation within the FTICR
      trapping cell and subsequent fragmentation induced by infrared multiphoton
      dissociation (IRMPD). Such a fragmentation was found very useful in terms of
      chemical identification of all precursor ions [M-H](-) including sulfur-rich GLSs
      reported here for the first time. Along with most common GLSs already found in
      capers such as glucocapparin, isopropyl/n-propyl-GLS, mercapto-glucocapparin, and
      two indolic GLS, i.e., 4-hydroxyglucobrassicin and glucobrassicin, the occurrence
      of the uncommon glycinyl-glucocapparin as well as two sulfur-rich GLSs is
      reported. IRMPD showed an increased selectivity towards disulfide bond cleavages
      with thiol migration, suggesting the side chain structure of non-targeted
      compounds, i.e., disulfanyl-glucocapparin and trisulfanyl-glucocapparin.
      Glucocapparin [2.05 +/- 0.25 mg/g, dry weight (dw)] was the most abundant GLS,
      followed by glucobrassicin (232 +/- 18 ug/g, dw) and 4-hydroxyglucobrassicin (89
      +/- 12 ug/g, dw). All other compounds were present at very low content ranging
      from 0.5 to 1.5 ug/g dw.

PMID- 22972785
TI  - LC/ESI-MS/MS analysis outlines the different fumonisin patterns produced by F.
      verticillioides in culture media and in maize kernels.
AB  - Fumonisins are a family of food-borne mycotoxins with a wide spectrum of
      toxicological activities, produced by Fusarium verticillioides. Twenty-eight
      fumonisin analogues have been characterised so far, which can be separated into
      four main groups, identified as fumonisin A, B, C and P, being fumonisin B the
      most widely occurring in maize and corn-based food. In this work, major and minor
      fumonisin analogues produced by F. verticillioides have been determined by the
      development of a suitable tandem mass spectrometry procedure for target compound
      identification and quantification. The method has been applied to the
      determination of the major fumonisins in culture media of F. verticillioides and
      in mouldy maize. In addition to the main fumonisins produced by F.
      verticillioides, also secondary compounds such as FB4, FB5, FAs and FCs have been
      detected in both fungal liquid cultures and contaminated maize samples. The use
      of this method for quantification of major and minor fumonisins may be useful for
      an exhaustive evaluation of their occurrence and toxicological relevance in food;
      moreover, it may be applied for a better definition of the fumonisin biosynthetic
      pathways in different growing media as well as in maize.

PMID- 22972786
TI  - Ultrahigh resolution mass spectrometry and accurate mass measurements for high
      throughput food lipids profiling.
AB  - In the present study, accurate mass measurements by ultrahigh resolution mass
      spectrometry with Orbitrap-Exactive working at resolving power R: 100,000 (m/z
      200, full width at half maximum) with an accuracy better than 2 ppm in all the
      mass range (m/z 200 to 2000) were used to show a detailed molecular composition
      of diverse edible oils and fats. Flow injection was used to introduce samples
      into the mass spectrometer, obtaining a complete analysis of each sample in less
      than 10 min, including blanks. Meticulous choice of organic solvents and
      optimization of the ion source and Orbitrap mass analyzer parameters were carried
      out, in order to achieve reproducible mass spectra giving reliable elemental
      compositions of the lipid samples and to prevent carry over. More than 200
      elemental compositions attributable to diacylglycerols, triacylglycerols (TAGs),
      and their oxidation products have been found in the spectra of food lipids from
      different origin. Several compounds with very close molecular mass could only be
      resolved through ultrahigh resolution, allowing detailed and robust TAG profiling
      with a high characterization potential.

PMID- 22972787
TI  - Characterization of cocoa liquors by GC-MS and LC-MS/MS: focus on alkylpyrazines
      and flavanols.
AB  - Flavor is one of the most important characteristics of chocolate products and is
      due to a complex volatile fraction, depending both on the cocoa bean genotype and
      the several processes occurring during chocolate production (fermentation,
      drying, roasting and conching). Alkylpyrazines are among the most studied
      volatiles, being one of the main classes of odorant compounds in cocoa products.
      In this work, a mass spectrometric approach was used for the comparison of cocoa
      liquors from different countries. A headspace solid-phase microextraction gas
      chromatography-mass spectrometry method was developed for the qualitative study
      of the volatile fraction; the standard addition method was then used for the
      quantitative determination of five pyrazines (2-methylpyrazine, 2,3
      dimethylpyrazine, 2,5-dimethylpyrazine, 2,3,5-trimethylpyrazine and
      tetramethylpyrazine). Satisfactory figures of merit were obtained: Limits of
      quantitation were in the range 0.1-2.7 ng/g; repeatability and reproducibility
      varied between 3% and 7% and between 8% and 14%, respectively. The total content
      of the pyrazines was remarkably different in the considered samples, ranging from
      99 to 708 ng/g. Tetramethylpyrazine showed the highest concentration in all
      samples, with a maximum value of 585 ng/g. A preliminary study was also performed
      on the nonvolatile fraction using LC-MS/MS, identifying some flavanols such as
      catechin, epicatechin and procyanidins.

PMID- 22972788
TI  - A liquid chromatography-mass spectrometry approach to study "glucosinoloma" in
      broccoli sprouts.
AB  - Glucosinolates are an important class of secondary plant metabolites, possessing
      health-promoting properties. Young broccoli plants are a very good source of
      glucosinolates with concentrations several times greater than in mature plants.
      The aim of our study was to develop a liquid chromatography-mass spectrometry and
      liquid chromatography/tandem mass spectrometry qualitative and quantitative
      method for the measure of glucosinolates in broccoli sprouts. The described
      method provides high sensitivity and specificity, allowing a rapid and
      simultaneous determination of 14 glucosinolates. The proposed method has been
      validated for eight glucosinolates: glucobrassicin, glucoraphanin, glucoiberin,
      glucoerucin, progoitrin, gluconapin, sinigrin and glucocheirolin. The linear
      range was 1-150 ug ml(-1), the intra-day and inter-day precision values are
      within 6% and 8% at the lower limit of quantification, while the overall recovery
      of the eight glucosinolates was 99 +/- 9%. This validated method was used
      successfully for analysis of glucosinolates content of broccoli sprouts grown in
      different conditions.

PMID- 22972789
TI  - Liquid chromatographic/electrospray ionization tandem mass spectrometric study of
      polyphenolic composition of four cultivars of Fragaria vesca L. berries and their
      comparative evaluation.
AB  - High-performance liquid chromatography coupled with ion spray mass spectrometry
      in the tandem mode with both negative and positive ionization was used for
      investigating a variety of polyphenolic compounds in four genotypes of Fragaria
      vesca berries. About 60 phenolic compounds belonging to the compound classes of
      phenolic acids, ellagitannins, ellagic acid derivatives, flavonols, monomeric and
      oligomeric flavanols, dihydrochalcones and anthocyanins were reported, providing
      for the first time a quite complete picture of polyphenolic composition of F.
      vesca berries. Some of the polyphenols herein investigated, such as a tris
      galloyl-hexahydroxydiphenoyl-hexose, two castalagin/vescalagin-like isomers and
      peonidin-malonylglucoside, were described for the first time. Principal component
      analysis applied on original HPLC-MS/MS data, acquired in multiple reaction
      monitoring mode, successfully discriminated the four investigated cultivars on
      the basis of their polyphenolic composition, highlighting the fundamental role of
      mass spectrometry for food characterization.

PMID- 22972790
TI  - Analytical investigations about the presence of prednisolone in cow urine.
AB  - Since 2008, the analyses carried out in the Lombardia region as part of National
      Residue Control Plans have evidenced unexpected frequent detection of the
      corticosteroid prednisolone (PRED) in cow urine samples taken to the
      slaughterhouse. Considering the scarce plausibility of these high frequent
      findings, analytical investigations were started to ascertain the real presence
      of this corticosteroid. The applied confirmatory method involved liquid
      chromatography low-resolution tandem mass spectrometry (triple quadrupole) as
      instrumental technique, and it was validated in compliance with the requirements
      of the Commission Decision 2002/657/EC. However, recently some criticism
      regarding Commission Decision 2002/657/EC identification criteria has been
      pointed out, experimentally demonstrating false positive results (wrong
      identification) although these criteria have been strictly observed. Therefore,
      considering the serious implications (i.e. the possibility that PRED could be
      considered endogenous in particular animal conditions), studies were carried out
      to investigate the reliability of PRED identification through the change of the
      chromatographic conditions (mobile phases, gradient and analytical column) of the
      confirmatory procedure routinely applied. Further confirmation came from the
      application of high-resolution mass spectrometry technique (MS(2) and MS(3)
      experiments) to analyze incurred cow urines samples. All the obtained results
      confirmed definitively the real presence of this corticosteroid excluding false
      positive findings in routine analysis. In addition, other experiments
      demonstrated that high-resolution mass spectrometers (Time of Flight and Orbitrap
      technologies) could be successfully applied to routine determination of steroid
      residues in biological fluids at very low concentrations (< 1 ug L(-1)).

PMID- 22972791
TI  - Targeted screening of pesticides, veterinary drugs and mycotoxins in bakery
      ingredients and food commodities by liquid chromatography-high-resolution single
      stage Orbitrap mass spectrometry.
AB  - In the food industry, it is frequently necessary to check the quality of an
      ingredient to decide whether to use it in production and/or to have an idea of
      the final possible contamination of the finished product. The current need to
      quickly separate and identify relevant contaminants within different classes,
      often with legal residue limits on the order of 1-100 ug kg(-1), has led to the
      need for more effective analytical methods. With thousands of organic compounds
      present in complex food matrices, the development of new analytical solutions
      leaned towards simplified extraction/clean-up procedures and chromatography
      coupled with mass spectrometry. Efforts must also be made regarding the
      instrumental phase to overcome sensitivity/selectivity limits and interferences.
      For this purpose, high-resolution full scan analysis in mass spectrometry is an
      interesting alternative to the traditional tandem mass approach. A fast method
      for extracting and purifying bakery matrices was therefore developed and combined
      with the exploitation of ultra-high-pressure liquid chromatography (UHPLC)
      coupled to a Orbitrap ExactiveTM high-resolution mass spectrometer (HRMS).
      Extracts of blank, naturally contaminated and fortified minicakes, prepared
      through a combined use of industrial and pilot plant production lines, were
      analyzed at different concentration levels (1-100 ug kg(-1)) of various
      contaminants: a limit of detection at 10 ug kg(-1) was possible for most of the
      analytes within all the categories analyzed, including pesticides, aflatoxins,
      trichothecene toxins and veterinary drugs. The application of accurate mass
      targeted screening described in this article demonstrates that current single
      stage HRMS analytical instrumentation is well equipped to meet the challenges
      posed by chemical contaminants in the screening of both bakery raw materials and
      finished products.

PMID- 22972792
TI  - Identification and assay of carbohydrates in olive drupes by cesium attachment
      electrospray tandem mass spectrometry (ESI-MS/MS).
AB  - Identification and assay of sugars in olive drupes during their ripening phase is
      evaluated by tandem mass spectrometry. Recent achievements have shown that the
      quality of an extra virgin olive oil can be directly correlated to the ripening
      degree of the drupes that is likely linked to their saccharides content. An
      innovation in this peculiar food chain is now proposed that considers a high
      throughput assessment of the carbohydrate content by a recently introduced
      protocol based on the gas-phase chemistry of sugar-cesium adducts by ESI-MS/MS.

PMID- 22972793
TI  - Endogenous lipase catalyzed transesterification of olive oil fats. The formation
      of isomeric and oligomeric triacyleglycerols.
AB  - The role of lipase to catalyze hydrolysis and transesterification of
      triacylglycerols (TAGs) was evaluated in model systems as well as in virgin olive
      oil. Tandem mass spectrometry was applied in the identification of modified TAGs,
      ionized by electrospray, formed during the incubation of selected TAGs with mono
      and di carboxylic acids. The oligomerization of TAGs was observed in authentic
      olive oil samples and verified in model systems under catalysis exerted by
      lipase, whose presence in olive oil was already documented. The hydrolytic
      pathways taken under enzymatic treatment is balanced by the formation of TAG
      oligomers that should not alter the nutritional value of the aliment.

PMID- 22972794
TI  - Quantifying foot function in individuals with rheumatoid arthritis: recent
      advances and clinical implications.

PMID- 22972795
TI  - Survey of the WHO-REMPAN network's capability for strengthening preparedness for
      radiological and nuclear emergencies.
AB  - This paper investigates the capacity of the World Health Organization (WHO)
      REMPAN network in responding to radiological incidents and nuclear emergencies. A
      survey developed by the WHO Secretariat and Nagasaki University was sent to all
      40 WHO-REMPAN collaborating centres and liaison institutes in order to verify the
      current situation of the network, identify needs and collect suggestions for
      future improvements. Most of the responding institutions said they were satisfied
      with the current status of the network. However, several responses to the survey
      indicate that better internal communication is needed, as well as a position
      document to specify the roles, rights and responsibilities of the network
      members.

PMID- 22972796
TI  - Comparing Geant4 hadronic models for the WENDI-II rem meter response function.
AB  - The WENDI-II rem meter is one of the most popular neutron dosemeters used to
      assess a useful quantity of radiation protection, namely the ambient dose
      equivalent. This is due to its high sensitivity and its energy response that
      approximately follows the conversion function between neutron fluence and ambient
      dose equivalent in the range of thermal to 5 GeV. The simulation of the WENDI-II
      response function with the Geant4 toolkit is then perfectly suited to compare low
      and high-energy hadronic models provided by this Monte Carlo code. The results
      showed that the thermal treatment of hydrogen in polyethylene for neutron <4 eV
      has a great influence over the whole detector range. Above 19 MeV, both Bertini
      Cascade and Binary Cascade models show a good correlation with the results found
      in the literature, while low-energy parameterised models are not suitable for
      this application.

PMID- 22972797
TI  - Radiation dose in coronary CT angiography associated with prospective ECG
      triggering technique: comparisons with different CT generations.
AB  - A retrospective analysis was performed in patients undergoing prospective ECG
      triggered coronary computed tomography (CT) angiography (CCTA) with the single
      source 64-slice CT (SSCT), dual-source 64-slice CT (DSCT), dual-source 128-slice
      CT and 320-slice CT with the aim of comparing the radiation dose associated with
      different CT generations. A total of 164 patients undergoing prospective ECG
      triggered CCTA with different types of CT scanners were studied with the mean
      effective doses estimated at 6.8 +/- 3.2, 4.2 +/- 1.9, 4.1+/-0.6 and 3.8 +/- 1.4
      mSv corresponding to the 128-slice DSCT, 64-slice DSCT, 64-slice SSCT and 320
      slice CT scanners. In this study a positive relationship was found between the
      effective dose and the body mass index (BMI). A low radiation dose is achieved in
      prospective ECG-triggered CCTA, regardless of the CT scanner generation. BMI is
      identified as the major factor that has a direct impact on the effective dose
      associated with prospective ECG-triggered CCTA.

PMID- 22972798
TI  - Reassessment of structural shielding design in mammography installations.
AB  - In this article, it is argued that current shielding methodologies can lead to an
      over-shielding of low-energy X-ray imaging facilities. Measurements of scattered
      air kerma rates in a mammography installation, including the effect of an
      anthropomorphic phantom of the patient, are presented. Detailed Monte Carlo
      calculations that support the measured results are also shown. Calculations for a
      mobile mammography installation, including the 'patient transmission factor', are
      presented and results are discussed.

PMID- 22972799
TI  - New susceptibility breakpoints and the regional variability of MIC distribution
      in Mycobacterium tuberculosis isolates.

PMID- 22972800
TI  - Mesenchymal stem cells and cardiac regeneration: a sophisticated approach depends
      on trophic effects--what's left over? Focus on "Activation of Toll-like receptor
      3 amplifies mesenchymal stem cell trophic factors and enhances therapeutic
      potency".

PMID- 22972801
TI  - Pannexin1 contributes to pathophysiological ATP release in lipoapoptosis induced
      by saturated free fatty acids in liver cells.
AB  - Hepatocyte lipoapoptosis induced by saturated free fatty acids (FFA) contributes
      to hepatic inflammation in lipotoxic liver injury, and the cellular mechanisms
      involved have not been defined. Recent studies have shown that apoptosis in
      nonhepatic cells stimulates ATP release via activation of pannexin1 (panx1), and
      extracellular ATP functions as a proinflammatory signal for recruitment and
      activation of the inflammatory cells. However, it is not known whether
      lipoapoptosis stimulates ATP release in liver cells. We found that lipoapoptosis
      induced by saturated FFA stimulated ATP release in liver cells that increased
      extracellular ATP concentration by more than fivefold above the values observed
      in healthy cells. This sustained pathophysiological ATP release was not dependent
      on caspase-3/7 activation. Inhibition of c-Jun NH(2)-terminal kinase (JNK), a key
      mediator of lipoapoptosis, with SP600125 blocked pathophysiological ATP release
      in a dose-dependent manner. RT-PCR analysis indicated that panx1 is expressed in
      hepatocytes and multiple liver cell lines. Notably, inhibition of panx1
      expression with short hairpin (sh)RNA inhibited in part pathophysiological ATP
      release. Moreover, lipoapoptosis stimulated uptake of a membrane impermeable dye
      YoPro-1 (indicative of panx1 activation), which was inhibited by panx1 shRNA,
      probenecid, and mefloquine. These results suggest that panx1 contributes to
      pathophysiological ATP release in lipoapoptosis induced by saturated FFA. Thus
      panx1 may play an important role in hepatic inflammation by mediating an increase
      in extracellular ATP concentration in lipotoxic liver injury.

PMID- 22972802
TI  - VDAC: old protein with new roles in diabetes.
AB  - A decrease in capillary density due to an increase in endothelial cell apoptosis
      in the heart is implicated in cardiac ischemia in diabetes. The voltage-dependent
      anion channel (VDAC) plays a crucial role in the regulation of mitochondrial
      metabolic function and mitochondria-mediated apoptosis. This study is designed to
      examine the role of VDAC in coronary endothelial dysfunction in diabetes.
      Endothelial cells (ECs) were more apoptotic in diabetic left ventricle of
      diabetic mice and mouse coronary ECs (MCECs) isolated from diabetic mice
      exhibited significantly higher mitochondrial Ca(2+) concentration and VDAC
      protein levels than control MCECs. The expression of VDAC-short hairpin RNA
      (shRNA) not only decreased the resting mitochondrial Ca(2+) concentration but
      also attenuated mitochondrial Ca(2+) uptake in diabetic MCECs. Furthermore, the
      downregulation of VDAC in diabetic MCECs significantly decreased mitochondrial
      superoxide anion (O(2)(-)) production and the activity of the mitochondrial
      permeability transition pore (mPTP) opening (an indirect indicator of cell
      apoptosis) toward control levels. These data suggest that the increased VDAC
      level in diabetic MCECs is responsible for increased mitochondrial Ca(2+)
      concentration, mitochondrial O(2)(-) production, and mPTP opening activity.
      Normalizing VDAC protein level may help to decrease endothelial cell apoptosis,
      increase capillary density in the heart, and subsequently decrease the incidence
      of cardiac ischemia in diabetes.

PMID- 22972804
TI  - The benefits and harms of mammographic screening for breast cancer: building the
      evidence base using service screening programmes.

PMID- 22972805
TI  - The potential for systematic early detection and treatment of breast cancer to
      reduce the burden of disease is widely recognized in the European Union (EU).
      Introduction.

PMID- 22972803
TI  - Prolonged exposure to methylglyoxal causes disruption of vascular KATP channel by
      mRNA instability.
AB  - Diabetes mellitus is characterized by hyperglycemia and excessive production of
      intermediary metabolites including methylglyoxal (MGO), a reactive carbonyl
      species that can lead to cell injuries. Interacting with proteins, lipids, and
      DNA, excessive MGO can cause dysfunction of various tissues, especially the
      vascular walls where diabetic complications often take place. However, the
      potential vascular targets of excessive MGO remain to be fully understood. Here
      we show that the vascular Kir6.1/SUR2B isoform of ATP-sensitive K(+) (K(ATP))
      channels is likely to be disrupted with an exposure to submillimolar MGO. Up to
      90% of the Kir6.1/SUR2B currents were suppressed by 1 mM MGO with a time constant
      of ~2 h. Consistently, MGO treatment caused a vast reduction of both Kir6.1 and
      SUR2B mRNAs endogenously expressed in the A10 vascular smooth muscle cells. In
      the presence of the transcriptional inhibitor actinomycin-D, MGO remained to
      lower the Kir6.1 and SUR2B mRNAs to the same degree as MGO alone, suggesting that
      the MGO effect is likely to compromise the mRNA stability. Luciferase reporter
      assays indicated that the 3'-untranslated regions (UTRs) of the Kir6.1 but not
      SUR2 mRNA were targeted by MGO. In contrast, the SUR2B mRNAs obtained with in
      vitro transcription were disrupted by MGO directly, while the Kir6.1 transcripts
      were unaffected. Consistent with these results, the constriction of mesenteric
      arterial rings was markedly augmented with an exposure to 1 mM MGO for 2 h, and
      such an MGO effect was totally eliminated in the presence of glibenclamide. These
      results therefore suggest that acting on the 3'-UTR of Kir6.1 and the coding
      region of SUR2B, MGO causes instability of Kir6.1 and SUR2B mRNAs, disruption of
      vascular K(ATP) channels, and impairment of arterial function.

PMID- 22972806
TI  - Summary of the evidence of breast cancer service screening outcomes in Europe and
      first estimate of the benefit and harm balance sheet.
AB  - OBJECTIVES: To construct a European 'balance sheet' of key outcomes of population
      based mammographic breast cancer screening, to inform policy-makers, stakeholders
      and invited women. METHODS: From the studies reviewed, the primary benefit of
      screening, breast cancer mortality reduction, was compared with the main harms,
      over-diagnosis and false-positive screening results (FPRs). RESULTS: Pooled
      estimates of breast cancer mortality reduction among invited women were 25% in
      incidence-based mortality studies and 31% in case-control studies (38% and 48%
      among women actually screened). Estimates of over-diagnosis ranged from 1% to 10%
      of the expected incidence in the absence of screening. The combined estimate of
      over-diagnosis for screened women, from European studies correctly adjusted for
      lead time and underlying trend, was 6.5%. For women undergoing 10 biennial
      screening tests, the estimated cumulative risk of a FPR followed by non-invasive
      assessment was 17%, and 3% having an invasive assessment. For every 1000 women
      screened biennially from age 50-51 until age 68-69 and followed up to age 79, an
      estimated seven to nine lives are saved, four cases are over-diagnosed, 170 women
      have at least one recall followed by non-invasive assessment with a negative
      result and 30 women have at least one recall followed by invasive procedures
      yielding a negative result. CONCLUSIONS: The chance of saving a woman's life by
      population-based mammographic screening of appropriate quality is greater than
      that of over-diagnosis. Service screening in Europe achieves a mortality benefit
      at least as great as the randomized controlled trials. These outcomes should be
      communicated to women offered service screening in Europe.

PMID- 22972807
TI  - The impact of mammographic screening on breast cancer mortality in Europe: a
      review of observational studies.
AB  - OBJECTIVES: To assess the impact of population-based mammographic screening on
      breast cancer mortality in Europe, considering different methodologies and
      limitations of the data. METHODS: We conducted a systematic literature review of
      European trend studies (n = 17), incidence-based mortality (IBM) studies (n = 20)
      and case-control (CC) studies (n = 8). Estimates of the reduction in breast
      cancer mortality for women invited versus not invited and/or for women screened
      versus not screened were obtained. The results of IBM studies and CC studies were
      each pooled using a random effects meta-analysis. RESULTS: Twelve of the 17 trend
      studies quantified the impact of population-based screening on breast cancer
      mortality. The estimated breast cancer mortality reductions ranged from 1% to 9%
      per year in studies reporting an annual percentage change, and from 28% to 36% in
      those comparing post- and prescreening periods. In the IBM studies, the pooled
      mortality reduction was 25% (relative risk [RR] 0.75, 95% confidence interval
      [CI] 0.69-0.81) among invited women and 38% (RR 0.62, 95% CI 0.56-0.69) among
      those actually screened. The corresponding pooled estimates from the CC studies
      were 31% (odds ratio [OR] 0.69, 95% CI 0.57-0.83), and 48% (OR 0.52, 95% CI 0.42
      0.65) adjusted for self-selection. CONCLUSIONS: Valid observational designs are
      those where sufficient longitudinal individual data are available, directly
      linking a woman's screening history to her cause of death. From such studies, the
      best 'European' estimate of breast cancer mortality reduction is 25-31% for women
      invited for screening, and 38-48% for women actually screened. Much of the
      current controversy on breast cancer screening is due to the use of inappropriate
      methodological approaches that are unable to capture the true effect of
      mammographic screening.

PMID- 22972808
TI  - The impact of mammographic screening on breast cancer mortality in Europe: a
      review of trend studies.
AB  - OBJECTIVE: Analysing trends in population breast cancer mortality statistics
      appears a simple method of estimating the effectiveness of mammographic screening
      programmes. We reviewed such studies of population-based screening in Europe to
      assess their value. METHODS: A literature review identified 17 papers, of which
      12 provided quantitative estimates of the impact of screening. Due to differences
      in comparisons and outcome measures, no pooled estimate of effectiveness was
      calculated. RESULTS: Comparisons included breast cancer mortality before and
      after the introduction of screening, trends in early and late starting areas and
      trends in age groups affected and unaffected by screening. Studies that
      calculated the percentage annual change after the start of screening found
      reductions of 1-9% per year (1%, 2.3-2.8% and 9% for those with adequate follow
      up). Of studies that compared mortality in time periods before and after
      introduction of screening, three single country studies all had adequate follow
      up and estimated mortality reductions ranging from 28% to 36%. Limitations of
      studies of population mortality rates include the inability to exclude deaths in
      women with breast cancer diagnosed before invitation to screening, diluting any
      observable impact of screening, and the gradual implementation of screening in a
      country or region. CONCLUSIONS: Although analysing population breast cancer
      mortality rates over time can be a first step in examining changes following the
      introduction of screening, this method is of limited value for assessment of
      screening impact. Other methods and individual data are necessary to properly
      quantify the effect.

PMID- 22972809
TI  - Breast cancer mortality in mammographic screening in Europe: a review of
      incidence-based mortality studies.
AB  - OBJECTIVES: To estimate the impact of service mammography screening on breast
      cancer mortality using European incidence-based mortality (IBM) studies (or
      refined mortality studies). IBM studies include only breast cancer deaths
      occurring in women with breast cancer diagnosed after their first invitation to
      screening. METHODS: We conducted a literature review and identified 20
      publications based on IBM studies. They were classified according to the method
      used for estimating the expected breast cancer mortality in the absence of
      screening: (1) women not yet invited; (2) historical data from the same region as
      well as from historical and current data from a region without screening; and (3)
      historical comparison group combined with data for non-participants. RESULTS: The
      estimated effect of mammography screening on breast cancer mortality varied
      across studies. The relative risks were 0.76-0.81 in group 1; 0.75-0.90 in group
      2; and 0.52-0.89 in group 3. Study databases overlapped in both Swedish and
      Finnish studies, adjustment for lead time was not optimal in all studies, and
      some studies had other methodological limitations. There was less variability in
      the relative risks after allowing for the methodological shortcomings.
      CONCLUSIONS: Based on evidence from the most methodologically sound IBM studies,
      the most likely impact of European service mammography screening programmes was a
      breast cancer mortality reduction of 26% (95% confidence interval 13-36%) among
      women invited for screening and followed up for 6-11 years.

PMID- 22972810
TI  - Overdiagnosis in mammographic screening for breast cancer in Europe: a literature
      review.
AB  - OBJECTIVES: Overdiagnosis, the detection through screening of a breast cancer
      that would never have been identified in the lifetime of the woman, is an adverse
      outcome of screening. We aimed to determine an estimate range for overdiagnosis
      of breast cancer in European mammographic service screening programmes. METHODS:
      We conducted a literature review of observational studies that provided estimates
      of breast cancer overdiagnosis in European population-based mammographic
      screening programmes. Studies were classified according to the presence and the
      type of adjustment for breast cancer risk (data, model and covariates used), and
      for lead time (statistical adjustment or compensatory drop). We expressed
      estimates of overdiagnosis from each study as a percentage of the expected
      incidence in the absence of screening, even if the variability in the age range
      of the denominator could not be removed. Estimates including carcinoma in situ
      were considered when available. RESULTS: There were 13 primary studies reporting
      16 estimates of overdiagnosis in seven European countries (the Netherlands,
      Italy, Norway, Sweden, Denmark, UK and Spain). Unadjusted estimates ranged from
      0% to 54%. Reported estimates adjusted for breast cancer risk and lead time were
      2.8% in the Netherlands, 4.6% and 1.0% in Italy, 7.0% in Denmark and 10% and 3.3%
      in England and Wales. CONCLUSIONS: The most plausible estimates of overdiagnosis
      range from 1% to 10%. Substantially higher estimates of overdiagnosis reported in
      the literature are due to the lack of adjustment for breast cancer risk and/or
      lead time.

PMID- 22972811
TI  - False-positive results in mammographic screening for breast cancer in Europe: a
      literature review and survey of service screening programmes.
AB  - OBJECTIVE: To estimate the cumulative risk of a false-positive screening result
      in European mammographic screening programmes, and examine the rates and
      procedures of further assessment. METHODS: A literature review was conducted to
      identify studies of the cumulative risk of a false-positive result in European
      screening programmes (390,000 women). We then examined aggregate data, cross
      sectional information about further assessment procedures among women with
      positive results in 20 mammographic screening programmes from 17 countries (1.7
      million initial screens, 5.9 million subsequent screens), collected by the
      European Network for Information on Cancer project (EUNICE). RESULTS: The
      estimated cumulative risk of a false-positive screening result in women aged 50
      69 undergoing 10 biennial screening tests varied from 8% to 21% in the three
      studies examined (pooled estimate 19.7%). The cumulative risk of an invasive
      procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%).
      The risk of undergoing surgical intervention with benign outcome was 0.9% (one
      study only). From the EUNICE project, the proportions of all screening
      examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for
      initial and subsequent screens, respectively, though the rates differed between
      countries; the corresponding rates of surgical interventions among women without
      breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative
      procedures following a recall should be considered when examining the cumulative
      risk of a false-positive screening result. Most women with a positive screening
      test undergo a non-invasive assessment procedure. Only a small proportion of
      recalled women undergo needle biopsy, and even fewer undergo surgical
      intervention.

PMID- 22972812
TI  - Communicating the balance sheet in breast cancer screening.
AB  - OBJECTIVE: Despite the difficulties, there is a moral responsibility to provide
      the public with the best estimates of benefits and harms of breast cancer
      screening. METHODS: In this paper we review the issues in communication of
      benefits and harms of medical interventions and discuss these in terms of the
      principles of the balance sheet proposed in this supplement. RESULTS: The balance
      sheet can be seen as a tool to convey estimates based on the best available
      evidence and addressed to a readership wider than just potential screening
      participants. It reflects a re-assessment of screening efficacy, showing again
      that screening is effective and brings more benefits than harms. It can be viewed
      as an opportunity to re-affirm some basic principles of good evidence-based
      communication. Further research is needed to improve communication strategy, to
      assess the impact of this communication on women's awareness and to evaluate its
      utility in the informed decision-making process. CONCLUSION: The balance sheet
      could be a starting point for a broader vision of informed decision-making in
      screening, which should also recognize the role played by 'non-numerical' factors
      on women's choice of participating in breast cancer screening.

PMID- 22972813
TI  - Mammographic screening programmes in Europe: organization, coverage and
      participation.
AB  - OBJECTIVES: To summarize participation and coverage rates in population
      mammographic screening programmes for breast cancer in Europe. METHODS: We used
      the European Network for Information on Cancer (EUNICE), a web-based data
      warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer
      screening, to obtain information on programme characteristics, coverage and
      participation from its initial application in 10 national and 16 regional
      programmes in 18 European countries. RESULTS: The total population targeted by
      the screening programme services covered in the report comprised 26.9 million
      women predominantly aged 50-69. Most of the collected data relates to 2005, 2006
      and/or 2007. The average participation rate across all programmes was 53.4%
      (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large
      programme that initiated personal invitations in 2007. Thirteen of the 26
      programmes achieved the European Union benchmark of acceptable participation
      (>70%), nine achieved the desirable level (>75%). Despite considerable invitation
      coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4
      92.1%) of the target population were actually screened. The overall invitation
      and examination coverage excluding Poland was 70.9% and 50.3%, respectively.
      CONCLUSIONS: The results demonstrate the feasibility of European-wide screening
      monitoring using the EBCSM data warehouse, although further efforts to refine the
      system and to harmonize standards and data collection practices will be required,
      to fully integrate all European countries. The more than three-fold difference in
      the examination coverage should be taken into account in the evaluation of
      service screening programmes.

PMID- 22972814
TI  - Emergence of Klebsiella pneumoniae and Salmonella metallo-beta-lactamase (NDM-1)
      producers on reunion island.

PMID- 22972815
TI  - John C. Sherris, M.D.

PMID- 22972816
TI  - Molecular analysis of Acinetobacter baumannii isolates from invasive infections
      in 2009 in Poland.

PMID- 22972817
TI  - Characterization of methicillin-resistant Staphylococcus aureus strains recovered
      from a phase IV clinical trial for linezolid versus vancomycin for treatment of
      nosocomial pneumonia.
AB  - A total of 434 methicillin-resistant Staphylococcus aureus (MRSA) baseline
      isolates were collected from subjects enrolled in a prospective, double-blind
      randomized trial comparing linezolid versus vancomycin for the treatment of
      nosocomial pneumonia. Isolates were susceptibility tested by broth microdilution,
      examined for inducible clindamycin resistance by D-test, and screened for
      heterogeneous resistance to vancomycin (hVISA) by the Etest macromethod. All
      strains were subjected to Panton-Valentine leukocidin (PVL) screening, and
      SCCmec, pulsed-field gel electrophoresis (PFGE), and spa typing. Selected strains
      were evaluated by multilocus sequence typing (MLST). Clonal complexes (CCs) were
      assigned based on the spa and/or MLST results. Most strains were CC5 (56.0%),
      which originated from North America (United States) (CC5-MRSA-SCCmec II/IV;
      70.0%), Asia (CC5-MRSA-II; 14.0%) and Latin America (CC5-MRSA-I/II; 12.3%). The
      second- and third-most-prevalent clones were CC8-MRSA-IV (23.3%) and CC239-MRSA
      III (11.3%), respectively. Furthermore, the CC5-MRSA-I/II clone predominated in
      Asia (50.7% within this region) and Latin America (66.7%), followed by CC239-MRSA
      III (32.8% and 28.9%, respectively). The European strains were CC8-MRSA-IV
      (34.5%), CC22-MRSA-IV (18.2%), or CC5-MRSA-I/II/IV (16.4%), while the U.S. MRSA
      isolates were CC5-MRSA-II/IV (64.4%) or CC8-MRSA-IV (28.8%). Among the U.S. CC8
      MRSA-II/IV strains, 73.7% (56/76 [21.2% of all U.S. MRSA strains]) clustered
      within USA300. One strain from the United States (USA800) was intermediate to
      vancomycin (MIC, 4 MUg/ml). All remaining strains were susceptible to linezolid,
      daptomycin, vancomycin, and teicoplanin. hVISA strains (14.5%) were predominantly
      CC5-MRSA-II, from South Korea, and belonged to a single PFGE type. Overall, each
      region had two predominant clones. The USA300 rate corroborates previous reports
      describing increased prevalence of USA300 strains causing invasive infections.
      The prevalence of hVISA was elevated in Asia, and these strains were associated
      with CC5.

PMID- 22972818
TI  - Novel primer-probe sets for detection and identification of mycobacteria by PCR
      microarray assay.
AB  - A PCR-microarray assay was developed in which PCR primers and hybridization
      probes were designed for the 16S rRNA genes of 16 clinically relevant
      mycobacteria and for IS6110 of Mycobacterium tuberculosis. The assay, based on a
      multiplex PCR followed by hybridization with oligonucleotide probes, was tested
      against 16 Mycobacterium species and 70 clinical samples.

PMID- 22972819
TI  - Mixed mucosal leishmaniasis infection caused by Leishmania tropica and Leishmania
      major.
AB  - Mixed infections with different Leishmania species could explain differences in
      the clinical courses of these infections. On identification of Leishmania
      parasites from Iranian patients with mucosal leishmaniasis (ML), a patient with
      both oral and nasal lesions was found to be concomitantly infected with
      Leishmania tropica and L. major. Mixed infection was identified by PCR
      amplification of Leishmania kinetoplast DNA on scraping of cytological smears and
      histopathological sections. L. major and L. tropica were isolated from the nasal
      and oral lesions, respectively. These species were also confirmed by
      immunohistochemistry. This seems to be the first reported case of concurrent ML
      infection with two Leishmania species. It indicates that, at least in this
      patient, previous infection with one of these Leishmania species did not protect
      against infection with the other. This result has important implications for the
      development of vaccines against leishmaniases and implies careful attention in
      the treatment of this infectious disease.

PMID- 22972820
TI  - Epidemiology and genotypic characteristics of methicillin-resistant
      Staphylococcus aureus strains of porcine origin.
AB  - The main goal of this study was to determine the prevalence of methicillin
      resistant Staphylococcus aureus (MRSA), particularly livestock-associated MRSA
      (LA-MRSA) in pigs and pork.  The genotypic relatedness of isolates on the farm,
      at slaughter, and at the retail level was assessed. Paired nasal and perianal
      swab samples were collected from 10 cohorts of market-age pigs (24 pigs per
      cohort) and carcasses at slaughterhouse, and pork samples were collected at
      retail. Staphylococci were isolated using selective enrichment method. Isolates
      were tested for antimicrobial resistance by broth microdilution. Duplex PCR was
      used to confirm MRSA using species-specific (nuc) and methicillin resistance
      (mecA) genes. The clonal relatedness of isolates was determined using pulsed
      field gel electrophoresis (PFGE), Staphylococcus protein A (spa) typing,
      multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec
      element (SCCmec) typing. MRSA was detected in 5 of the 10 cohorts (50%), with the
      prevalence ranging from 0% to 12.5% per cohort. Of all the pigs sampled on the
      farm before they went to market, 3% (7/240) were MRSA positive. A higher
      prevalence of MRSA was detected at holding pens at the slaughterhouse (11%
      [27/240]). MRSA was also detected in 2% (4/235) of the carcasses and 4% (5/135)
      of the retail pork. While the isolates appear predominantly to be highly clonal,
      PFGE had a relatively higher discriminatory power (discriminatory index [DI]  =
      0.624). Four genotypic clusters were identified by PFGE; of the four clusters,
      clonal type B was predominant across the farm-to-retail continuum. MLST findings
      revealed that sequence type 5 (ST5) was the most predominant subtype (32/50). The
      livestock-associated MRSA (clonal complex 398 [CC398] or sequence type 398
      [ST398]) was the second common type (12/50) and was detected at all stages from
      farm to retail. Nine of the 50 (18%) MRSA isolates belonged to spa type 539/t034
      that were of ST398 based on MLST. The results of this study confirm that MRSA,
      including LA-MRSA, is common in herds of swine in Ohio and hereby shown to
      persist in the farm to processing and retail continuum.

PMID- 22972821
TI  - Molecular epidemiology of outbreak-associated and wild-waterfowl-derived
      newcastle disease virus strains in Finland, including a novel class I genotype.
AB  - Newcastle disease (ND) is a highly contagious, severe disease of poultry caused
      by pathogenic strains of Newcastle disease virus (NDV; or avian paramyxovirus-1).
      NDV is endemic in wild birds worldwide and one of the economically most important
      poultry pathogens. Most of the published strains are outbreak-associated strains,
      while the apathogenic NDV strains that occur in wild birds, posing a constant
      threat to poultry with their capability to convert into more virulent forms, have
      remained less studied. We screened for NDV RNA in cloacal and oropharyngeal
      samples from wild waterfowl in Finland during the years 2006 to 2010: 39 of 715
      birds were positive (prevalence, 5.5%). The partial or full-length F genes of 37
      strains were sequenced for phylogenetic purposes. We also characterized viruses
      derived from three NDV outbreaks in Finland and discuss the relationships between
      these outbreak-associated and the wild-bird-associated strains. We found that all
      waterfowl NDV isolates were lentogenic strains of class I or class II genotype I.
      We also isolated a genetically distinct class I strain (teal/Finland/13111/2008)
      grouping phylogenetically together with only strain HIECK87191, isolated in
      Northern Ireland in 1987. Together they seem to form a novel class I genotype
      genetically differing from other known NDVs by at least 12%.

PMID- 22972822
TI  - Performance characteristics of the Cepheid Xpert vanA assay for rapid
      identification of patients at high risk for carriage of vancomycin-resistant
      Enterococci.
AB  - We compared the performance characteristics of culture and the Cepheid Xpert vanA
      assay for routine surveillance of vancomycin-resistant enterococci (VRE) from
      rectal swabs in patients at high risk for VRE carriage. The Cepheid Xpert vanA
      assay had a limit of detection of 100 CFU/ml and correctly detected 101 well
      characterized clinical VRE isolates with no cross-reactivity in 27 non-VRE and
      related culture isolates. The clinical sensitivity, specificity, positive
      predictive value, and negative predictive value of the Xpert vanA PCR assay were
      100%, 96.9%, 91.3%, and 100%, respectively, when tested on 300 consecutively
      collected rectal swabs. This assay provides excellent predictive values for
      prompt identification of VRE-colonized patients in hospitals with relatively high
      rates of VRE carriage.

PMID- 22972823
TI  - Production of KPC-2 alone does not always result in beta-lactam MICs representing
      resistance in gram-negative pathogens.

PMID- 22972824
TI  - Antimicrobial treatment and containment measures for an extremely drug-resistant
      Klebsiella pneumoniae ST101 isolate carrying pKPN101-IT, a novel fully sequenced
      bla(KPC-2) plasmid.
AB  - An extremely drug-resistant Klebsiella pneumoniae isolate, sequence type ST101,
      was isolated from a patient in Italy. We describe antibiotic treatment, measures
      to clear and contain the infection, and a complete sequence analysis of a novel
      large plasmid, pKPN101-IT, harboring the bla(KPC-2) gene and arising from the
      threatening recombination of different worldwide-distributed backbones.

PMID- 22972825
TI  - Isolation of Kerstersia gyiorum from a patient with cholesteatomatous chronic
      otitis media.
AB  - We describe the first case of a Kerstersia gyiorum strain isolated from a patient
      with cholesteatomatous chronic otitis media. We emphasize the isolation of
      members of the family Alcaligenaceae in serious infections and unusual sites and
      the importance of polyphasic identification addressing the definitive
      identification.

PMID- 22972826
TI  - The diagnostic performance of the GenoType MTBDRplus version 2 line probe assay
      is equivalent to that of the Xpert MTB/RIF assay.
AB  - Molecular diagnostics for Mycobacterium tuberculosis have recently been endorsed
      by the World Health Organization. The Xpert MTB/RIF assay was endorsed for use on
      patient material, regardless of smear gradation, while the GenoType MTBDRplus
      (version 1) has been limited for use on smear-positive patient material. In this
      study, we evaluated the diagnostic performance of the Xpert MTB/RIF and GenoType
      MTBDRplus (version 2) assays on smear-positive and smear-negative patient
      specimens submitted to a high-throughput diagnostic laboratory. A total of 282
      consecutive specimens were subjected to the two new molecular assays, and their
      performance characteristics were assessed relative to the routine diagnostic
      standard. Both assays showed similar diagnostic performance characteristics. The
      sensitivities of the GenoType MTBDRplus (v2.0) and Xpert MTB/RIF assays for the
      detection of culture-positive M. tuberculosis were 73.1% and 71.2%, respectively,
      while the specificities of both assays were 100%. Both assays were able to
      diagnose the presence of M. tuberculosis in 57 to 58% of smear-negative cases,
      suggesting that the performance characteristics were dependent on bacillary load.
      The detection of M. tuberculosis in culture-negative specimens confirmed that
      molecular assays should not be used for treatment monitoring. The sensitivity and
      specificity for rifampin resistance detection were 100% in both assays; however,
      the GenoType MTBDRplus (v2.0) assay provided additional information on isoniazid
      susceptibility. The GenoType MTBDRplus (v2.0) assay will complement the Xpert
      MTB/RIF screening assay by validating rifampin susceptibility and providing
      information on isoniazid susceptibility. In addition, the GenoType MTBDRplus
      (v2.0) assay will provide pharmacogenetic information that may be critical in
      guiding appropriate treatment.

PMID- 22972828
TI  - Longitudinal analysis of the evolution and dissemination of Neisseria gonorrhoeae
      strains (Saskatchewan, Canada, 2005 to 2008) reveals three major circulating
      strains and convergent evolution of ciprofloxacin and azithromycin resistance.
AB  - A longitudinal study combining multilocus sequence typing with molecular
      evolutionary analysis determined the distribution, population structure, and
      evolution of antibiotic resistance in Neisseria gonorrhoeae isolates in
      Saskatchewan that were collected between 2005 and 2008. Of 195 gonococcal
      isolates examined, 29 sequence types (STs) were identified with 3 major
      circulating strains (ST-1 through ST-3) comprising 52% of all gonococcal isolates
      studied. The prevalences, persistence, distribution patterns, and clonalities of
      these isolates strongly suggest that gonorrhea endemicity within this broad
      geographic region was driven by these 3 circulating strains. ST-1 exhibited a
      significantly (P = 0.001) higher prevalence throughout the study than did the
      others, accounting for ~25% of the tested isolates each year. The spatial
      distributions of the gonococcal strains indicated that ST-1 in 2007 entered a
      linear component of the sexual network, reaching the remote north and resulting
      in the further spread and maintenance of infection. Ciprofloxacin and
      azithromycin resistances were observed in distantly related gonococcal lineages,
      clearly indicating the convergent acquisition of these antibiotic-resistant
      phenotypes. In addition, all ciprofloxacin- and azithromycin-resistant lineages
      were found at the edges of the minimum spanning tree, far from the major
      lineages, suggesting that these antibiotic phenotypes were most likely introduced
      into the province. In contrast, resistance to penicillin was found mostly in the
      endemic gonococcal lineages, suggesting that penicillin resistance was probably
      acquired in Saskatchewan as a result of spontaneous mutations in already
      established lineages. Tetracycline resistance was present in all STs except one,
      indicating its ubiquitous nature in the gonococcal population studied.

PMID- 22972829
TI  - Rapid detection of carbapenemase-producing Pseudomonas spp.
AB  - A novel biochemical technique, the Carba NP test, has been evaluated to detect
      carbapenemase production in Pseudomonas spp. This test was specific (100%),
      sensitive (94.4%), and rapid (<2 h). This cost-effective test, which could be
      implemented in any microbiology laboratory, offers a reliable technique for
      identification of carbapenemase-producing Pseudomonas spp.

PMID- 22972827
TI  - Clonal analysis of Neisseria meningitidis serogroup B strains in South Africa,
      2002 to 2006: emergence of new clone ST-4240/6688.
AB  - From August 1999 through July 2002, hyperinvasive Neisseria meningitidis
      serogroup B (MenB) clonal complexes (CCs),  namely, ST-32/ET-5  (CC32) and ST
      41/44/lineage 3 (CC41/44), were predominant in the Western Cape Province of South
      Africa. This study analyzed MenB invasive isolates from a national laboratory
      based surveillance system that were collected from January 2002 through December
      2006. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) (n =
      302), and multilocus sequence typing (MLST) and PorA and FetA typing were
      performed on randomly selected isolates (34/302, 11%). In total, 2,400 cases were
      reported, with the highest numbers from Gauteng Province (1,307/2,400, 54%) and
      Western Cape Province (393/2,400, 16%); 67% (1,617/2,400) had viable isolates and
      19% (307/1,617) were identified as serogroup B. MenB incidence remained stable
      over time (P = 0.77) (average incidence, 0.13/100,000 population [range, 0.10 to
      0.16/100,000 population]). PFGE (302/307, 98%) divided isolates (206/302, 68%)
      into 13 clusters and 96 outliers. The largest cluster, B1, accounted for 25% of
      isolates (76/302) over the study period; its prevalence decreased from 43%
      (20/47) in 2002 to 13% (8/62) in 2006 (P < 0.001), and it was common in the
      Western Cape (58/76, 76%). Clusters B2 and B3 accounted for 10% (31/302) and 6%
      (19/302), respectively, and showed no significant change over time and were
      predominant in Gauteng. Randomly selected isolates from clusters B1, B2, and B3
      belonged to CC32, CC41/44, and the new CC4240/6688, respectively. Overall, 15
      PorA and 12 FetA types were identified. MenB isolates were mostly diverse with no
      single dominant clone; however, CC32 and CC41/44 accounted for 35% and the new
      CC4240/6688 was the third most prevalent clone.

PMID- 22972830
TI  - Enteroaggregative Escherichia coli O78:H10, the cause of an outbreak of urinary
      tract infection.
AB  - In 1991, multiresistant Escherichia coli O78:H10 strains caused an outbreak of
      urinary tract infections in Copenhagen, Denmark. The phylogenetic origin, clonal
      background, and virulence characteristics of the outbreak isolates, and their
      relationship to nonoutbreak O78:H10 strains according to these traits and
      resistance profiles, are unknown. Accordingly, we extensively characterized 51
      archived E. coli O78:H10 isolates (48 human isolates from seven countries,
      including 19 Copenhagen outbreak isolates, and 1 each of calf, avian, and unknown
      source isolates), collected from 1956 through 2000. E. coli O78:H10 was clonally
      heterogeneous, comprising one dominant clonal group (61% of isolates, including
      all 19 outbreak isolates) from ST10 (phylogenetic group A) plus several minor
      clonal groups (phylogenetic groups A and D). All ST10 isolates, versus 25% of non
      ST10 isolates, were identified by molecular methods as enteroaggregative E. coli
      (EAEC) (P < 0.001). Genes present in >90% of outbreak isolates included fimH
      (type 1 fimbriae; ubiquitous in E. coli); fyuA, traT, and iutA (associated with
      extraintestinal pathogenic E. coli [ExPEC]); and sat, pic, aatA, aggR, aggA,
      ORF61, aaiC, aap, and ORF3 (associated with EAEC). An outbreak isolate was lethal
      in a murine subcutaneous sepsis model and exhibited characteristic EAEC "stacked
      brick" adherence to cultured epithelial cells. Thus, the 1991 Copenhagen outbreak
      was caused by a tight, non-animal-associated subset within a broadly disseminated
      O78:H10 clonal group (ST10; phylogenetic group A), members of which exhibit both
      ExPEC and EAEC characteristics, whereas O78:H10 isolates overall are
      phylogenetically diverse. Whether ST10 O78:H10 EAEC strains are both
      uropathogenic and diarrheagenic warrants further investigation.

PMID- 22972831
TI  - Production of 2-aminophenoxazin-3-one by Staphylococcus aureus causes false
      positive results in beta-galactosidase assays.
AB  - Staphylococcus aureus can be distinguished from similar coagulase-positive
      staphylococci by its absence of beta-galactosidase activity. This is commonly
      tested using o-nitrophenyl-beta-D-galactopyranoside (ONPG) as the substrate.
      Unexpectedly, 111 and 58 of 123 isolates displayed apparent beta-galactosidase
      activity in the ONPG assay and on the Vitek 2 system, respectively. Compositional
      analysis showed that the yellow coloration of the positive ONPG assay resulted
      from production of 2-aminophenoxazin-3-one. Alternative beta-galactosidase
      substrates like X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside)
      should be used for testing staphylococci.

PMID- 22972832
TI  - Molecular typing of Treponema pallidum: a 5-year surveillance in Shanghai, China.
AB  - Previously, a small study showed that 14f was the predominant subtype of
      Treponema pallidum in Shanghai, China. The result was quite different from the
      genotype distribution in other areas of China. This study aimed to identify the
      strain types of Treponema pallidum in samples collected over a 5-year period in
      Shanghai. From 2007 to 2011, genital swabs were collected from patients with
      syphilis from the Shanghai Skin Disease Hospital. Positive specimens were typed
      by the enhanced typing method by adding a tp0548 gene to the existing arp and tpr
      genotype system. In total, 304 of the 372 enrolled patients yielded fully
      typeable DNA. Ten arp types (4, 6, 8, 9, 11, 12, 13, 14, 15, and 19), 3 tpr types
      (a, d, and o), and 5 tp0548 types (a, c, f, g, and i) were identified. In total,
      12 subtypes were identified with a combination of the arp and tpr genes. Subtype
      14d was found in 270 samples (88.8%). When the combination included the tp0548
      gene, the 12 CDC subtypes identified were divided into 14 strain types. The
      predominant type was 14d/f (88.8%), followed by 15d/f (3.6%), 13d/f (1.3%), and
      19d/c (1.3%). Two of the 44 14d/f-infected patients and both of the 19d/c
      infected patients who underwent a lumbar puncture were diagnosed with
      neurosyphilis. This study showed that the predominant type in Shanghai was 14d/f.
      While this is in keeping with data from other areas in China, it is different
      from an earlier report showing that 14f is the most common genotype in Shanghai.
      Further studies are needed to better understand the association between strain
      types and neurosyphilis.

PMID- 22972833
TI  - Next-generation ion torrent sequencing of drug resistance mutations in
      Mycobacterium tuberculosis strains.
AB  - A novel protocol for full-length Mycobacterium tuberculosis gene analysis of
      first- and second-line drug resistance was developed using the Ion Torrent
      Personal Genome Machine (PGM). Five genes-rpoB (rifampin), katG (isoniazid), pncA
      (pyrazinamide), gyrA (ofloxacin/fluoroquinolone), and rrs (aminoglycosides)-were
      amplified and sequenced, and results were compared to those obtained by genotypic
      Hain line probe assay (LPA) and phenotypic Bactec MGIT 960 analysis using 26
      geographically diverse South African clinical isolates collected between July and
      November 2011. Ion Torrent sequencing exhibited 100% (26/26) concordance to
      phenotypic resistance obtained by MGIT 960 culture and genotypic rpoB and katG
      results by LPA. In several rifampin-resistant isolates, Ion Torrent sequencing
      revealed uncommon substitutions (H526R and D516G) that did not have a defined
      mutation by LPA. Importantly, previously uncharacterized mutations in rpoB
      (V194I), rrs (G878A), and pncA (Q122Stop) genes were observed. Ion Torrent
      sequencing may facilitate tracking and monitoring geographically diverse
      multidrug-resistant and extensively drug-resistant strains and could potentially
      be integrated into selected regional and reference settings throughout Africa,
      India, and China.

PMID- 22972834
TI  - Model analysis of the relationship between intracellular PO2 and energy demand in
      skeletal muscle.
AB  - On the basis of experimental studies, the intracellular O(2) (iPo(2))-work rate
      (WR) relationship in skeletal muscle is not unique. One study found that iPo(2)
      reached a plateau at 60% of maximal WR, while another found that iPo(2) decreased
      linearly at higher WR, inferring capillary permeability-surface area (PS) and
      blood-tissue O(2) gradient, respectively, as alternative dominant factors for
      determining O(2) diffusion changes during exercise. This relationship is affected
      by several factors, including O(2) delivery and oxidative and glycolytic
      capacities of the muscle. In this study, these factors are examined using a
      mechanistic, mathematical model to analyze experimental data from contracting
      skeletal muscle and predict the effects of muscle contraction on O(2) transport,
      glycogenolysis, and iPo(2). The model describes convection, O(2) diffusion, and
      cellular metabolism, including anaerobic glycogenolysis. Consequently, the model
      simulates iPo(2) in response to muscle contraction under a variety of
      experimental conditions. The model was validated by comparison of simulations of
      O(2) uptake with corresponding experimental responses of electrically stimulated
      canine muscle under different O(2) content, blood flow, and contraction
      intensities. The model allows hypothetical variation of PS, glycogenolytic
      capacity, and blood flow and predictions of the distinctive effects of these
      factors on the iPo(2)-contraction intensity relationship in canine muscle.
      Although PS is the main factor regulating O(2) diffusion rate, model simulations
      indicate that PS and O(2) gradient have essential roles, depending on the
      specific conditions. Furthermore, the model predicts that different convection
      and diffusion patterns and metabolic factors may be responsible for different
      iPo(2)-WR relationships in humans.

PMID- 22972835
TI  - Alterations in sleep architecture in response to experimental sleep curtailment
      are associated with signs of positive energy balance.
AB  - Sleep reduction is associated with increased energy intake and weight gain,
      though few studies have explored the relationship between sleep architecture and
      energy balance measures in the context of experimental sleep restriction.
      Fourteen males and 13 females (body mass index: 22-26 kg/m(2)) participated in a
      crossover sleep curtailment study. Participants were studied under two sleep
      conditions: short (4 h/night; 0100-0500 h) and habitual (9 h/night; 2200-0700 h),
      for 5 nights each. Sleep was polysomnographically recorded nightly. Outcome
      measures included resting metabolic rate (RMR), feelings of appetite-satiety, and
      ad libitum food intake. Short sleep resulted in reductions in stage 2 sleep and
      rapid eye movement (REM) sleep duration (P < 0.001), as well as decreased
      percentage of stage 2 sleep and REM sleep and increased slow wave sleep (SWS)
      percentage (P < 0.05). Linear mixed model analysis demonstrated a positive
      association between stage 2 sleep duration and RMR (P = 0.051). Inverse
      associations were observed between REM sleep duration and hunger (P = 0.031) and
      between stage 2 sleep duration and appetite for sweet (P = 0.015) and salty (P =
      0.046) foods. Stage 2 sleep percentage was inversely related to energy consumed
      (P = 0.024). Stage 2 sleep (P = 0.005), SWS (P = 0.008), and REM sleep (P =
      0.048) percentages were inversely related to fat intake, and SWS (P = 0.040) and
      REM sleep (P = 0.050) were inversely related to carbohydrate intake. This study
      demonstrates that changes in sleep architecture are associated with markers of
      positive energy balance and indicate a means by which exposure to short sleep
      duration and/or an altered sleep architecture profile may lead to excess weight
      gain over time.

PMID- 22972836
TI  - Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in
      resting heated humans.
AB  - Hypocapnia attenuates the sweat response normally seen in hyperthermic resting
      subjects, but its effect on the blood flow response in their nonglabrous skin
      under the same hyperthermic conditions remains unclear. In the present study, we
      investigated whether hypocapnia induced by voluntary hyperventilation affects the
      blood flow response to heat stress in the nonglabrous skin of resting humans.
      Nine healthy male subjects were passively heated using legs-only hot water
      immersion and a water-perfused suit, which caused esophageal temperature (T(es))
      to increase by as much as 1.0 degrees C. During normothermia and at +0.6 degrees
      C T(es) and +1.0 degrees C T(es), the subjects performed two voluntary 7-min
      hyperventilation (minute ventilation = 40 l/min) trials (hypocapnic and eucapnic)
      in random order. End-tidal CO(2) pressure was reduced by 23-25 torr during
      hypocapnic hyperventilation, but it was maintained at the spontaneous breathing
      level during eucapnic hyperventilation. Cutaneous blood flow was evaluated as the
      cutaneous red blood cell flux in the forearm (CBF(forearm)) or forehead
      (CBF(forehead)) and was normalized to the normothermic spontaneous breathing
      value. Hypocapnic hyperventilation at +0.6 degrees C T(es) was associated with
      significantly reduced CBF(forearm), compared with eucapnic hyperventilation,
      after 5-7 min of hyperventilation (395 to 429 vs. 487 to 525% baseline, P <
      0.05). No significant difference in CBF(forehead) was seen during hypocapnic
      hyperventilation compared with eucapnic hyperventilation at +0.6 degrees C T(es)
      or +1.0 degrees C T(es). These results suggest that in resting humans, hypocapnia
      achieved through voluntary hyperventilation attenuates the increase in cutaneous
      blood flow elicited by moderate heat stress in the nonglabrous skin of the
      forearm, but not the forehead.

PMID- 22972838
TI  - Temporal organization of activity in the brown bear (Ursus arctos): roles of
      circadian rhythms, light, and food entrainment.
AB  - Seasonal cycles of reproduction, migration, and hibernation are often
      synchronized to changes in daylength (photoperiod). Ecological and evolutionary
      pressures have resulted in physiological specializations enabling animals to
      occupy a particular temporal niche within the diel cycle leading to
      characteristic activity patterns. In this study, we characterized the annual
      locomotor activity of captive brown bears (Ursus arctos). Locomotor activity was
      observed in 18 bears of varying ages and sexes during the active (Mar-Oct) and
      hibernating (Nov-Feb) seasons. All bears exhibited either crepuscular or diurnal
      activity patterns. Estimates of activity duration (alpha) and synchronization to
      the daily light:dark cycle (phase angles) indirectly measured
      photoresponsiveness. alpha increased as daylength increased but diverged near the
      autumnal equinox. Phase angles varied widely between active and hibernating
      seasons and exhibited a clear annual rhythm. To directly test the role of
      photoperiod, bears were exposed to controlled photoperiod alterations. Bears
      failed to alter their daily activity patterns (entrain) to experimental
      photoperiods during the active season. In contrast, photic entrainment was
      evident during hibernation when the daily photocycle was shifted and when bears
      were exposed to a skeleton (11:1:11:1) photoperiod. To test whether entrainment
      to nonphotic cues superseded photic entrainment during the active season, bears
      were exposed to a reversed feeding regimen (dark-fed) under a natural photocycle.
      Activity shifted entirely to a nocturnal pattern. Thus daily activity in brown
      bears is highly modifiable by photoperiod and food availability in a stereotypic
      seasonal fashion.

PMID- 22972837
TI  - Isolated duodenal exclusion increases energy expenditure and improves glucose
      homeostasis in diet-induced obese rats.
AB  - Roux-en-Y gastric bypass (RYGB) in rodent models reduces food intake (FI),
      increases resting energy expenditure (EE), and improves glycemic control. We have
      shown that mimicking the duodenal component of RYGB by implantation of a 10-cm
      endoluminal sleeve device (ELS-10) induces weight loss and improves glycemic
      control in diet-induced obese (DIO) rats. We sought to determine the mechanisms
      and structural requirements of these effects. We examined the effects of ELS-10
      devices implanted in male DIO rats on body weight, food intake (FI), meal
      patterns, total and resting EE, and multiple parameters of glucose homeostasis,
      comparing them with sham-operated (SO) rats and with SO rats weight matched to
      the ELS-10-treated group. To determine the extent of duodenal exclusion required
      to influence metabolic outcomes, we compared the effects of implanting 10-, 4-,
      or 1-cm ELS devices. ELS-10 rats exhibited 13% higher total and 9% higher resting
      EE than SO controls. ELS-10 rats also exhibited enhanced postprandial GLP-1
      secretion and improved glucose tolerance and insulin sensitivity out of
      proportion to the effects of weight loss alone. Implantation of 4- or 1-cm ELS
      devices had no effect on EE and limited effects on glucose homeostasis. Complete
      duodenal exclusion with ELS-10 induces weight loss by decreasing FI and
      increasing EE and improves glycemic control through weight loss-independent
      mechanisms. Thus signals originating in the proximal small intestine appear to
      exert a direct influence on the physiological regulation of EE and glucose
      homeostasis. Their selective manipulation could provide effective new therapies
      for obesity and diabetes that mimic the benefits of RYGB.

PMID- 22972839
TI  - Modulation of vH+-ATPase is part of the functional adaptation of sheep rumen
      epithelium to high-energy diet.
AB  - Ruminal vacuolar H(+)-ATPase (vH(+)-ATPase) activity is regulated by metabolic
      signals. Thus, we tested whether its localization, expression, and activity were
      changed by different feeding. Young male sheep (n = 12) were either fed hay ad
      libitum (h) or hay ad libitum plus additional concentrate (h/c) for 2 wk. The
      vH(+)-ATPase B subunit signal was predominantly found in the cell membrane and
      cytosol of rumen epithelial cells (REC) with basal/parabasal phenotype. The
      elevated number (threefold) of these cells in rumen mucosa of h/c-fed sheep
      reflects a high proliferative capacity and, explains the 2.3-fold increase of the
      total number of vH(+)-ATPase-expressing REC. However, in accordance with a 58%
      reduction of the vH(+)-ATPase B subunit mRNA expression in h/c-fed sheep, its
      protein amount per single REC was decreased. Using the fluorescent probe BCECF
      and selective inhibitors (foliomycin, amiloride), the contribution of vH(+)
      ATPase and Na(+)/H(+) exchanger to intracellular pH (pH(i)) regulation was
      investigated. REC isolated from h/c-fed sheep keep their pH(i) at a significantly
      higher level (6.91 +/- 0.03 vs. 6.74 +/- 0.05 in h-fed sheep). Foliomycin or
      amiloride decreased pH(i) by 0.16 +/- 0.02 and 0.57 +/- 0.04 pH units when
      applied to REC from h-fed sheep, but the effects were markedly reduced (-88 and 
      33%) after concentrate feeding. Nevertheless, we found that REC proliferation
      rate and [cAMP](i) were reduced after foliomycin-induced vH(+)-ATPase inhibition.
      Our results provide the first evidence for a role of vH(+)-ATPase in regulation
      of REC proliferation, most probably by linking metabolically induced pH(i)
      changes to signaling pathways regulating this process.

PMID- 22972840
TI  - Stem cells, dot-com.
AB  - Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned
      because of the Internet. Despite very limited approval for use, DTC stem cell
      marketed "treatments" have emerged for an array of conditions, creating global
      public health and safety risks. However, it remains unclear whether such use of
      stem cells is subject to drugs or biologics regulations. To address this gap,
      regulatory agencies should be given clear authority, and the international
      community should create a framework for appropriate stem cell use. In addition,
      consumer protection laws should be used to scrutinize providers.

PMID- 22972841
TI  - Extrapolating from animals to humans.
AB  - Because of a variety of caveats, the safety and effectiveness of interventions in
      human subjects can only be speculated from animal studies. Careful synthesis of
      data from multiple animal studies is needed to begin to assess the likelihood of
      successful cross-species translation (Fay et al., this issue).

PMID- 22972842
TI  - Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum
      enrichment mediates rhinosinusitis.
AB  - Persistent mucosal inflammation and microbial infection are characteristics of
      chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other
      chronic inflammatory diseases; however, the relationship between sinus microbiota
      composition and CRS is unknown. Using comparative microbiome profiling of a
      cohort of CRS patients and healthy subjects, we demonstrate that the sinus
      microbiota of CRS patients exhibits significantly reduced bacterial diversity
      compared with that of healthy controls. In our cohort of CRS patients, multiple,
      phylogenetically distinct lactic acid bacteria were depleted concomitant with an
      increase in the relative abundance of a single species, Corynebacterium
      tuberculostearicum. We recapitulated the conditions observed in our human cohort
      in a murine model and confirmed the pathogenic potential of C. tuberculostearicum
      and the critical necessity for a replete mucosal microbiota to protect against
      this species. Moreover, Lactobacillus sakei, which was identified from our
      comparative microbiome analyses as a potentially protective species, defended
      against C. tuberculostearicum sinus infection, even in the context of a depleted
      sinus bacterial community. These studies demonstrate that sinus mucosal health is
      highly dependent on the composition of the resident microbiota as well as
      identify both a new sino-pathogen and a strong bacterial candidate for
      therapeutic intervention.

PMID- 22972843
TI  - Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in
      men who have sex with men.
AB  - Drug concentrations associated with protection from HIV-1 acquisition have not
      been determined. We evaluated drug concentrations among men who have sex with men
      in a substudy of the iPrEx trial (1). In this randomized placebo-controlled
      trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used
      as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was
      detected less frequently in blood plasma and in viable cryopreserved peripheral
      blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was
      first discovered compared with controls at the matched time point of the study
      (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%;
      P < 0.001). An intracellular concentration of the active form of tenofovir,
      tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with
      a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed
      dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that,
      when analyzed according to the iPrEx model, corresponded to an HIV-1 risk
      reduction of 76% for two doses per week, 96% for four doses per week, and 99% for
      seven doses per week. Prophylactic benefits were observed over a range of doses
      and drug concentrations, suggesting ways to optimize PrEP regimens for this
      population.

PMID- 22972844
TI  - Anthrax vaccine-induced antibodies provide cross-species prediction of survival
      to aerosol challenge.
AB  - Because clinical trials to assess the efficacy of vaccines against anthrax are
      not ethical or feasible, licensure for new anthrax vaccines will likely involve
      the Food and Drug Administration's "Animal Rule," a set of regulations that allow
      approval of products based on efficacy data only in animals combined with
      immunogenicity and safety data in animals and humans. U.S. government-sponsored
      animal studies have shown anthrax vaccine efficacy in a variety of settings. We
      examined data from 21 of those studies to determine whether an immunological
      bridge based on lethal toxin neutralization activity assay (TNA) can predict
      survival against an inhalation anthrax challenge within and across species and
      genera. The 21 studies were classified into 11 different settings, each of which
      had the same animal species, vaccine type and formulation, vaccination schedule,
      time of TNA measurement, and challenge time. Logistic regression models
      determined the contribution of vaccine dilution dose and TNA on prediction of
      survival. For most settings, logistic models using only TNA explained more than
      75% of the survival effect of the models with dose additionally included. Cross
      species survival predictions using TNA were compared to the actual survival and
      shown to have good agreement (Cohen's kappa ranged from 0.55 to 0.78). In one
      study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques
      (actual survival, 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These
      data add support for the use of TNA as an immunological bridge between species to
      extrapolate data in animals to predict anthrax vaccine effectiveness in humans.

PMID- 22972845
TI  - Comparative study on the histomorphology and molecular biology of radial artery
      conduits in patients with diabetes mellitus who underwent coronary bypass
      surgery.
AB  - We studied the impact of diabetes mellitus (DM) on the radial artery (RA) in 30
      patients with DM and 30 non-diabetic patients undergoing coronary artery bypass
      grafting with autologous RA. RAs were recorded as normal if there was no cellular
      or stromal tissue between the endothelium and the internal elastic lamina. The RA
      was normal in 26.7% of diabetic and 76.7% of non-diabetic patients (p =
      0.000298). Intimal thickness index and intima:media ratio were higher in the
      former than in the latter (p < 0.05; p < 0.05), with no significant difference in
      luminal narrowing (p > 0.05). Electron microscopy scores were lower in the non
      diabetic group (p < 0.001); endothelial nitric oxide synthase (eNOS) protein
      expression and optical density were higher (p < 0.001). Von Willebrand factor and
      endothelin-1 messenger RNA (mRNA) levels were higher in the DM patients (p <
      0.001). The quality of the RA in patients with DM was thus inferior to that in
      non-diabetic patients. Care should be taken when selecting RA as a conduit in
      patients with DM.

PMID- 22972846
TI  - Multiparameter in vitro assessment of compound effects on cardiomyocyte
      physiology using iPSC cells.
AB  - A large percentage of drugs fail in clinical studies due to cardiac toxicity;
      thus, development of sensitive in vitro assays that can evaluate potential
      adverse effects on cardiomyocytes is extremely important for drug development.
      Human cardiomyocytes derived from stem cell sources offer more clinically
      relevant cell-based models than those presently available. Human-induced
      pluripotent stem cell-derived cardiomyocytes are especially attractive because
      they express ion channels and demonstrate spontaneous mechanical and electrical
      activity similar to adult cardiomyocytes. Here we demonstrate techniques for
      measuring the impact of pharmacologic compounds on the beating rate of
      cardiomyocytes with ImageXpress Micro and FLIPR Tetra systems. The assays employ
      calcium-sensitive dyes to monitor changes in Ca(2+) fluxes synchronous with cell
      beating, which allows monitoring of the beat rate, amplitude, and other
      parameters. We demonstrate here that the system is able to detect concentration
      dependent atypical patterns caused by hERG inhibitors and other ion channel
      blockers. We also show that both positive and negative chronotropic effects on
      cardiac rate can be observed and IC(50) values determined. This methodology is
      well suited for safety testing and can be used to estimate efficacy and dosing of
      drug candidates prior to clinical studies.

PMID- 22972847
TI  - High-content imaging in cervical cancer screening.
AB  - A shift from conventional cytology to a molecular approach could improve cervical
      cancer screening. This proof-of-concept study aims to develop a high-content
      imaging platform for the simultaneous detection of multiple biomarkers for
      cervical disease. Liquid-based cytology (LBC) samples were used to optimize a
      dual ProExC/Ki-67 immunofluorescence staining protocol for SurePath-fixed cells.
      The simultaneous and automated detection of these biomarkers was performed using
      the BD Pathway 435 system. The ability of high-content imaging to detect
      dysplastic cervical cells was assessed using keratinocytes spiked with
      immunopositive SiHa cells and a high-grade squamous intraepithelial lesion (HSIL)
      LBC sample. The percentages of Ki-67- and ProExC-immunopositive objects
      correlated significantly with the percentages of spiked SiHa cells. The
      dysplastic cells of the HSIL sample could be detected using high-content cell
      analysis. In conclusion, high-content imaging allows the simultaneous and
      automated detection of Ki-67- and ProExC-immunopositive dysplastic cells in LBC
      specimens.

PMID- 22972848
TI  - A high-throughput assay to identify small-molecule modulators of alternative pre
      mRNA splicing.
AB  - Alternative splicing (AS) is an efficient mechanism that involves the generation
      of transcriptome and protein diversity from a single gene. Defects in pre
      messenger RNA (mRNA) splicing are an important cause of numerous diseases,
      including cancer. AS of pre-mRNA as a target for cancer therapy has not been well
      studied. We have reported previously that a splicing factor, polypyrimidine tract
      binding protein (PTB), is overexpressed in ovarian tumors compared with matched
      normal controls, and knockdown of PTB expression by short-hairpin RNA impairs
      ovarian tumor cell growth, colony formation, and invasiveness. Given the
      complexity of PTB's molecular functions, a chemical method for controlling PTB
      activity might provide a therapeutic and experimental tool. However, no
      commercially available PTB inhibitors have yet been described. To expand our
      ability to find novel inhibitors, we developed a robust, fluorometric, cell-based
      high-throughput screening assay in 96-well plates that reports on the splicing
      activity of PTB. In an attempt to use the cells for large-scale chemical screens
      to identify PTB modulators, we established cell lines stably expressing the
      reporter gene. Our results suggest that this high-throughput assay could be used
      to identify small-molecule modulators of PTB activity. Based on these findings
      and the role that upregulated PTB has on cell proliferation and malignant
      properties of tumors, targeting PTB for inhibition with small molecules offers a
      promising strategy for cancer therapy.

PMID- 22972849
TI  - The effect of smoking on ligament and cartilage surgery in the knee: a systematic
      review.
AB  - BACKGROUND: The adverse effects of smoking on various health conditions such as
      cancer, diabetes, and cardiovascular disease have been well documented. Many
      orthopaedic conditions, such as fracture healing, wound repair, and bone mineral
      density, have been reported to be adversely affected by smoking. However, no
      known systematic reviews have investigated the effects of smoking on ligament and
      cartilage knee surgery. PURPOSE: We hypothesized that smoking would have a
      negative influence from both a basic science and clinical outcome perspective on
      these types of knee surgeries. STUDY DESIGN: Systematic review. METHODS: A
      systematic review of multiple medical databases was performed evaluating clinical
      and basic science studies to determine the effects of smoking on ligament and
      cartilage knee surgery. RESULTS: Fourteen studies were found for inclusion and
      analysis. Eight of these studies addressed the relationship between smoking and
      knee ligaments, and 6 investigated the relationship between smoking and articular
      cartilage. With the exception of 1, all of the basic science and clinical studies
      exploring the relationship between smoking and knee ligaments found a negative
      association of smoking, either molecularly, biomechanically, or clinically. One
      basic science and 3 clinical studies found a negative influence of smoking on
      articular cartilage of the knee. No studies were found that investigated the
      relationship of smoking and menisci. CONCLUSION: The current literature reveals a
      negative influence of smoking on the results of knee ligament surgery, both from
      a basic science and clinical perspective, implying that smoking cessation would
      benefit patients undergoing these procedures. The association between smoking and
      knee articular cartilage was less clear, although the literature still suggests
      an overall negative influence and highlights the need for further investigation.

PMID- 22972850
TI  - The prevalence of low back pain among former elite cross-country skiers, rowers,
      orienteerers, and nonathletes: a 10-year cohort study.
AB  - BACKGROUND: Some cross-sectional studies have suggested that the prevalence of
      low back pain (LBP) may be high among endurance athletes with repetitive back
      loading, but there are no large, prospective cohort studies addressing this
      issue. PURPOSE: To compare the prevalence of symptoms of low back pain (LBP)
      among former endurance athletes with different loading characteristics on the
      lumbar region: cross-country skiing (flexion loading), rowing (extension
      loading), and orienteering (no specific loading), as well as a nonathletic
      control group. STUDY DESIGN: Cohort study; level of evidence, 2. METHODS: Self
      reported questionnaire on LBP adapted for sports based on standardized Nordic
      questionnaires for musculoskeletal symptoms. Responders were 173 rowers, 209
      orienteerers, 242 cross-country skiers, and 116 control subjects (88% of the
      original cohort). RESULTS: There were no group differences between the athletic
      groups and the control group with regard to the 2 main outcomes: reported LBP the
      previous 12 months (P = .66) and frequent LBP the past year (>30 days with LBP)
      (P = .14). More rowers than orienteerers reported frequent LBP the past year
      (adjusted OR = 2.32; CI, 1.02-5.28). Occupational changes due to LBP were
      reported more often by rowers (13%) than skiers (7%) and orienteerers (3%) (P =
      .002). More rowers and skiers reported having received outpatient medical
      assistance than orienteerers or controls. A training volume >550 h/y was a risk
      factor for reporting LBP during the previous 12 months compared with a training
      volume <200 h/y (adjusted OR = 2.51; CI, 1.26-5.02). A previous episode with LBP
      was associated with LBP later in life (adjusted OR = 3.02; CI, 2.22-4.10).
      CONCLUSION: Low back pain was not more common among former endurance athletes
      with specific back loading compared with non-athletes. The results indicate that
      years of prolonged and repetitive flexion or extension loading in endurance
      sports does not lead to more LBP. However, a large training volume in the past
      year and previous episodes with LBP are risk factors for LBP. Comparing the
      sports of rowing, cross-country skiing, and orienteering, it appears that whereas
      orienteering is protective, rowing can provoke LBP.

PMID- 22972851
TI  - Correlation of a single assessment numeric evaluation (SANE) rating with modified
      Cincinnati knee rating system and IKDC subjective total scores for patients after
      ACL reconstruction or knee arthroscopy.
AB  - BACKGROUND: Limited studies exist regarding how well a single assessment numeric
      evaluation (SANE) rating correlates with validated knee surveys. PURPOSE: To
      determine whether a SANE rating correlates positively with the International Knee
      Documentation Committee (IKDC) and the modified Cincinnati Knee Rating System
      (CKRS) total scores after knee surgery. STUDY DESIGN: Cohort study (Diagnosis);
      Level of evidence, 2. METHODS: Patients undergoing either anterior cruciate
      ligament (ACL) reconstruction or knee arthroscopy were prospectively given
      subjective evaluations yearly after surgery between January 2000 and June 2011.
      Subjective evaluations were obtained using modified CKRS and IKDC subjective knee
      surveys and a SANE rating. Interclass correlation coefficient was used to
      determine the correlation of the SANE rating to the survey total scores. Bland
      Altman method was used to access precision and limits of agreement between
      scores. In addition, the data were analyzed according to sex and age categories
      (<18, 18-24, 25-40, >40 years). RESULTS: A total of 11,939 surveys were collected
      from 3209 patients (mean, 3.7 surveys/person; range, 1-22) after ACL
      reconstruction with a mean survey age of 35.2 +/- 11.9 years (range, 13-72). A
      total of 4615 surveys were collected from 1813 patients (mean, 2.6
      surveys/person; range, 1-17) after knee arthroscopy with a mean survey age of
      47.4 +/- 14.6 years (range, 11-88). For patients who underwent ACL
      reconstruction, the SANE rating had a moderate positive correlation of 0.66 to
      the total survey scores. For patients who underwent knee arthroscopies, the SANE
      rating had a strong positive correlation of 0.74 to total scores. There was
      minimal difference in correlations based on age group or sex. Bland-Altman
      analysis showed that the limits of agreement between the SANE score and the 2
      surveys were met for at least 94% of patients in both patient groups. CONCLUSION:
      The SANE ratings exhibited moderate to strong positive correlations with the
      modified CKRS and IKDC subjective surveys after ACL reconstruction and knee
      arthroscopy for patients of all ages and both sexes.

PMID- 22972852
TI  - Improved osteochondral allograft preservation using serum-free media at body
      temperature.
AB  - BACKGROUND: Osteochondral allografts (OCAs) are currently preserved at 4 degrees
      C and used within 28 days of donor harvest. The window of opportunity for
      implantation is limited to 14 days due to a 2-week disease testing protocol.
      HYPOTHESIS: Osteochondral allograft tissues stored at 37 degrees C will have
      significantly higher chondrocyte viability, as well as superior biochemical and
      biomechanical properties, than those stored at 4 degrees C. STUDY DESIGN:
      Controlled laboratory study. METHODS: Osteochondral allografts from 15 adult
      canine cadavers were aseptically harvested within 4 hours of death. Medial and
      lateral femoral condyles were stored in Media 1, similar to the current standard,
      or Media 2, an anti-inflammatory and chondrogenic media containing dexamethasone
      and transforming growth factor-beta3, at 4 degrees C or 37 degrees C for up to 56
      days. Chondrocyte viability, glycosaminoglycan (GAG) and collagen (hydroxyproline
      [HP]) content, biomechanical properties, and collagen II and aggrecan content
      were assessed at days 28 and 56. Five femoral condyles were stored overnight and
      assessed the next day to serve as controls. RESULTS: Storage in Media 1 at 37
      degrees C maintained chondrocyte viability at significantly higher levels than in
      any other media-temperature combination and at levels not significantly different
      from controls. Osteochondral allografts stored in either media at 4 degrees C
      showed a significant decrease in chondrocyte viability throughout storage.
      Glycosaminoglycan and HP content were maintained through 56 days of storage in
      OCAs in Media 1 at 37 degrees C. There were no significant differences in elastic
      or dynamic moduli among groups at day 56. Qualitative immunohistochemistry
      demonstrated the presence of collagen II and aggrecan throughout all layers of
      cartilage. CONCLUSION: Osteochondral allograft viability, matrix content and
      composition, and biomechanical properties were maintained at "fresh" levels
      through 56 days of storage in Media 1 at 37 degrees C. Osteochondral allografts
      stored at 4 degrees C were unable to maintain viability or matrix integrity
      through 28 days of storage. These findings suggest that storage of OCAs in a
      defined media at 37 degrees C is superior to current protocols (4 degrees C) for
      tissue preservation prior to transplantation. CLINICAL RELEVANCE: Storage of OCAs
      in serum-free chemically defined media at 37 degrees C can increase the "window
      of opportunity" for implantation of optimal tissue from 14 days to 42 days after
      disease testing clearance.

PMID- 22972853
TI  - Repair of lateral meniscus posterior horn detachment lesions: a biomechanical
      evaluation.
AB  - BACKGROUND: Posterior horn detachment (PHD) lesions of the lateral meniscus are
      commonly associated with acute anterior cruciate ligament (ACL) tears. Multiple
      surgeons have advocated for repair of this lesion at the time of ACL
      reconstruction. However, the biomechanical consequences of this lesion and its
      subsequent repair have not been evaluated. HYPOTHESIS: The PHD lesion of the
      lateral meniscus will lead to increased tibiofemoral contact pressures, and
      repair of this lesion to bone via a tibial tunnel can restore normal contact
      pressures during simulated gait. STUDY DESIGN: Controlled laboratory study.
      METHODS: Lateral compartment contact pressures were measured via a sensor on the
      tibial plateau in 8 cadaver knees with the knee intact, after sectioning the
      posterior horn of the lateral meniscus to simulate PHD, and after repairing the
      injury. The repair was performed using an ACL tunnel guide to drill a tunnel from
      the anteromedial tibia to the posterior horn attachment site. Dynamic pressure
      data were continuously collected using a conductive ink pressure sensing system
      while each knee was moved through a physiological gait flexion cycle. RESULTS:
      Posterior horn detachment caused a significant increase in tibiofemoral peak
      contact pressure from 2.8 MPa to 4.2 MPa (P = .03). After repair of the lesion to
      bone was performed through a transtibial tunnel, the peak contact pressure was
      2.9 MPa. Posterior horn detachment also significantly decreased the maximum
      contact area over which tibiofemoral pressure is distributed from 451 mm(2) in
      the intact state to 304 mm(2) in the detached state. Repair of the PHD lesion
      increased the maximum contact area to 386 mm(2), however, this area was also
      significantly less than in the intact state (P = .05). CONCLUSION: Posterior horn
      detachment of the lateral meniscus causes increased peak tibiofemoral contact
      pressure. The peak pressure can be reduced to a normal level with repair of the
      lesion to bone via a transtibial tunnel. CLINICAL RELEVANCE: Posterior horn
      detachment of the lateral meniscus is a lesion often associated with an acute ACL
      tear. Debate exists concerning the importance of repairing PHD lesions at the
      time of ACL reconstruction. The data provided in this study may influence
      surgeons' management of the lesion.

PMID- 22972854
TI  - Interventions designed to prevent anterior cruciate ligament injuries in
      adolescents and adults: a systematic review and meta-analysis.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injuries are common, result in
      significant morbidity, and are expensive to repair surgically and to
      rehabilitate. Several randomized and observational studies have tested
      neuromuscular interventions as preventive measures for these injuries. PURPOSE:
      To conduct a systematic review and meta-analysis of all known comparative studies
      for estimating and testing the effect of neuromuscular and educational
      interventions on the incidence of ACL injuries in adolescents and adults, both
      male and female. STUDY DESIGN: Systematic review and meta-analysis. METHODS:
      Several databases were used to identify eligible studies through July 4, 2011:
      MEDLINE, EMBASE, SPORTDiscus, Cumulative Index to Nursing and Allied Health
      Literature, the Cochrane Central Register of Controlled Trials, and Health
      Technology Assessment. Eligible studies were assessed for risk of bias, and meta
      analyses were performed on the estimated intervention effect (log incidence rate
      ratio) using inverse-variance weighting, subgroup analysis, and random-effects
      meta-regression to estimate the overall (pooled) effect and explore heterogeneity
      of effect across studies (measured by I2 and tested with the Q statistic).
      RESULTS: Eight cohort (observational) studies and 6 randomized trials were
      included, involving a total of approximately 27,000 participants. The random
      effects meta-analysis yielded a pooled rate-ratio estimate of 0.485 (95%
      confidence interval [CI], 0.299-0.788; P = .003), indicating a lower ACL rate in
      the intervention groups, but there was appreciable heterogeneity of the estimated
      effect across studies (I2 = 64%; P = .001). In the meta-regressions, the
      estimated effect was stronger for studies that were not randomized, performed in
      the United States, conducted in soccer players, had a longer duration of follow
      up (more than 1 season), and had more hours of training per week in the
      intervention group, better compliance, and no dropouts. Nevertheless, residual
      heterogeneity was still observed within subgroups of those variables (I2 > 50%; P
      < .10). CONCLUSION: The authors found that various types of neuromuscular and
      educational interventions appear to reduce the incidence rate of ACL injuries by
      approximately 50%, but the estimated effect varied appreciably among studies and
      was not able to explain most of that variability. CLINICAL RELEVANCE:
      Neuromuscular and educational interventions appear to reduce the incidence rate
      of ACL injuries by approximately 50%.

PMID- 22972855
TI  - An analysis of specific lower extremity injury rates on grass and FieldTurf
      playing surfaces in National Football League Games: 2000-2009 seasons.
AB  - BACKGROUND: Players in the National Football League (NFL) sustain injuries every
      season as the result of their participation. One factor associated with the rate
      of injury is the type of playing surface on which the players participate.
      HYPOTHESIS: There is no difference in the rate of knee sprains and ankle sprains
      during NFL games when comparing rates of those injuries during games played on
      natural grass surfaces with rates of those injuries during games played on the
      artificial surface FieldTurf. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: The NFL records injury and exposure (ie, game) data as part of its
      injury surveillance system. During the 2000-2009 NFL seasons, there were 2680
      games (5360 team games) played on grass or artificial surfaces. Specifically,
      1356 team games were played on FieldTurf and 4004 team games were played on
      grass. We examined the 2000-2009 game-related injury data from those games as
      recorded by the injury surveillance system. The data included the injury
      diagnosis, the date of injury, and the surface at the time of injury. The injury
      data showed that 1528 knee sprains and 1503 ankle sprains occurred during those
      games. We calculated injury rates for knee sprains and ankle sprains
      specifically, medial collateral ligament (MCL) sprains, anterior cruciate
      ligament (ACL) sprains, eversion ankle sprains, and inversion ankle sprains-using
      incidence density ratios (IDRs). We used a Poisson model and logistic regression
      odds ratios to validate the IDR analysis. A multivariate logistic regression
      model was used to adjust the odds ratio for weather conditions. RESULTS: The
      observed injury rate of knee sprains on FieldTurf was 22% (IDR = 1.22, 95%
      confidence interval [CI], 1.09-1.36) higher than on grass, and the injury rate of
      ankle sprains on FieldTurf was 22% (IDR = 1.22, 95% CI, 1.09-1.36) higher than on
      grass. These differences are statistically significant. Specifically, the
      observed injury rates of ACL sprains and eversion ankle sprains on FieldTurf
      surfaces were 67% (P < .001) and 31% (P < .001) higher than on grass surfaces and
      were statistically significant. The observed injury rates of MCL sprains and
      inversion ankle sprains were also not significantly higher on FieldTurf surfaces
      (P = .689 and .390, respectively). CONCLUSION: Injury rates for ACL sprains and
      eversion ankle sprains for NFL games played on FieldTurf were higher than rates
      for those injuries in games played on grass, and the differences were
      statistically significant.

PMID- 22972856
TI  - Comparative effectiveness of injection therapies in lateral epicondylitis: a
      systematic review and network meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Injection therapy with glucocorticoids has been used since the 1950s
      as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several
      novel injection therapies have become available. PURPOSE: To assess the
      comparative effectiveness and safety of injection therapies in patients with
      lateral epicondylitis. STUDY DESIGN: Systematic review and meta-analysis.
      METHODS: Randomized controlled trials comparing different injection therapies for
      lateral epicondylitis were included provided they contained data for change in
      pain intensity (primary outcome). Trials were assessed using the Cochrane risk of
      bias tool. Network (random effects) meta-analysis was applied to combine direct
      and indirect evidence within and across trial data using the final end point
      reported in the trials, and results for the arm-based network analyses are
      reported as standardized mean differences (SMDs). RESULTS: Seventeen trials (1381
      participants; 3 [18%] at low risk of bias) assessing injection with 8 different
      treatments-glucocorticoid (10 trials), botulinum toxin (4 trials), autologous
      blood (3 trials), platelet-rich plasma (2 trials), and polidocanol,
      glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)-were
      included. Pooled results (SMD [95% confidence interval]) showed that beyond 8
      weeks, glucocorticoid injection was no more effective than placebo (-0.04 [-0.45
      to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk
      of bias. Although botulinum toxin showed marginal benefit (-0.50 [-0.91 to 
      0.08]), it caused temporary paresis of finger extension, and all trials were at
      high risk of bias. Both autologous blood (-1.43 [-2.15 to -0.71]) and platelet
      rich plasma (-1.13 [-1.77 to -0.49]) were also statistically superior to placebo,
      but only 1 trial was at low risk of bias. Prolotherapy (-2.71 [-4.60 to -0.82])
      and hyaluronic acid (-5.58 [-6.35 to -4.82]) were both more efficacious than
      placebo, whereas polidocanol (0.39 [-0.42 to 1.20]) and glycosaminoglycan (-0.32
      [-1.02 to 0.38]) showed no effect compared with placebo. The criteria for low
      risk of bias were only met by the prolotherapy and polidocanol trials.
      CONCLUSION: This systematic review and network meta-analysis of randomized
      controlled trials found a paucity of evidence from unbiased trials on which to
      base treatment recommendations regarding injection therapies for lateral
      epicondylitis.

PMID- 22972858
TI  - Editorial commentary: infections due to macrolide-resistant Mycoplasma
      pneumoniae: now what?

PMID- 22972857
TI  - Dental composites and amalgam and physical development in children.
AB  - Resin-based composite dental restoration materials may release bisphenol-A, an
      endocrine-disrupting chemical. Using secondary analysis of a randomized clinical
      safety trial of amalgam vs. composites, we tested the hypothesis that dental
      restoration materials affect children's growth. Children (N = 218 boys, N = 256
      girls) aged 6 to 10 yrs at baseline with >= 2 decayed posterior teeth were
      randomized to amalgam or composites (bisphenol-A-diglycidyl-dimethacrylate
      composite for permanent teeth, urethane-dimethacrylate compomer for primary
      teeth) for treatment of posterior caries throughout follow-up. Primary outcomes
      for this analysis were 5-year changes in BMI-for-age z-scores, body fat
      percentage (BF%), and height velocity; exploratory analyses (n = 113) examined
      age at menarche. Results showed no significant differences between treatment
      assignment and changes in physical development in boys [(composites vs. amalgam)
      BF%, 4.9 vs. 5.7, p = 0.49; (BMI-z-score) 0.13 vs. 0.25, p = 0.36] or girls (8.8
      vs. 7.7, p = 0.95; 0.36 vs. 0.21, p = 0.49). Children with more treatment on
      primary teeth had greater increases in BF% regardless of material type. Girls
      assigned to composites had lower risk of menarche during follow-up (hazard ratio
      = 0.57, 95% CI 0.35-0.95). Overall, there were no significant differences in
      physical development over 5 years in children treated with composites or amalgam.
      Additional studies examining these restoration materials in relation to age at
      menarche are warranted (clinicaltrials.gov number NCT00065988).

PMID- 22972860
TI  - Reply to Ison et Al.

PMID- 22972861
TI  - Patient-level data provide additional insight for tigecycline all-cause mortality
      meta-analysis.

PMID- 22972863
TI  - Response to several recent publications related to safety and efficacy of
      peramivir from the emergency use authorization experience.

PMID- 22972862
TI  - Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior
      active tuberculosis.
AB  - BACKGROUND: Active tuberculosis is common among human immunodeficiency virus
      (HIV)-infected persons living in tuberculosis-endemic areas, but the hazard of
      subsequent tuberculosis disease has not been quantified in a single prospective
      cohort. METHODS: Among HIV-infected, BCG-immunized adults with CD4 counts >=200
      cells/MUL who received placebo in the DarDar tuberculosis vaccine trial in
      Tanzania, we compared the prospective risk of active tuberculosis between
      subjects who did and who did not report prior active tuberculosis. All subjects
      with a positive tuberculin skin test without prior active tuberculosis were
      offered isoniazid preventive treatment. Definite or probable tuberculosis was
      diagnosed during active follow-up using rigorous published criteria. RESULTS: We
      diagnosed 52 cases of definite and 92 cases of definite/probable tuberculosis
      among 979 subjects during a median follow-up of 3.2 years. Among the 80 subjects
      who reported prior active tuberculosis, 11 (13.8%) subsequently developed
      definite tuberculosis and 17 (21.3%) developed definite/probable tuberculosis,
      compared with 41 (4.6%) and 75 (8.3%), respectively, of 899 subjects without
      prior active tuberculosis (definite tuberculosis risk ratio [RR], 3.01; 95%
      confidence interval [CI], 1.61-5.63, P < .001; definite/probable tuberculosis RR,
      2.55; 95% CI, 1.59-4.09, P < .001). In a Cox regression model adjusting for age,
      CD4 count, and isoniazid receipt, subjects with prior active tuberculosis had
      substantially greater hazard of subsequent definite tuberculosis (hazard radio
      [HR], 3.69; 95% CI, 1.79-7.63, P < .001) and definite/probable tuberculosis (HR,
      2.78; 95% CI, 1.58-4.87, P < .001). CONCLUSIONS: Compared to subjects without
      prior tuberculosis, the hazard of active tuberculosis is increased 3-fold among
      HIV-infected adults with prior active tuberculosis. Clinical Trials Registration.
      NCT0052195.

PMID- 22972864
TI  - Acute otitis media replacement and recurrence in the Finnish otitis media vaccine
      trial.
AB  - We reanalyzed the 7-valent pneumococcal conjugate vaccine trial FinOM for
      prevention of acute otitis media (AOM), with a focus on disease replacement due
      to other pathogens and AOM recurrence. We found evidence of replacement disease
      occurring early during the trial follow-up and little vaccine impact on recurrent
      overall AOM episodes.

PMID- 22972865
TI  - Editorial commentary: 027, 078, and others: going beyond the numbers (and away
      from the hypervirulence).

PMID- 22972867
TI  - Rapid effectiveness of minocycline or doxycycline against macrolide-resistant
      Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children.
AB  - BACKGROUND: Mycoplasma pneumoniae is a major pathogen causing community-acquired
      pneumonia in children and young adults. Outbreaks typically occur at intervals of
      several years. In 2011, a widespread outbreak was associated with macrolide
      resistant M. pneumoniae (MRMP) in Japanese children, often those of school age.
      METHODS: Two hundred fifty-eight children were diagnosed with M. pneumoniae
      associated pneumonia based on chest radiography, real-time polymerase chain
      reaction (PCR), and antibody titers between January and December 2011. Mycoplasma
      pneumoniae cultures obtained from nasopharyngeal samples using appropriate broth
      were subjected to real-time PCR, by which decreases in M. pneumoniae in patients
      treated with minocycline (MIN), doxycycline (DOX), or tosufloxacin (TFX) were
      calculated. Mutations of the 23S ribosomal RNA gene that confer high resistance
      to macrolides in M. pneumoniae were identified by DNA sequencing. RESULTS: Among
      202 M. pneumoniae isolates from M. pneumoniae-associated pneumonia patients, 176
      (87.1%) were MRMP. Macrolide-resistant M. pneumoniae infection was significantly
      related to school age (P < .01) and initial administration of macrolides (P <
      .01). Minocycline or DOX (n = 125) or TFX or levofloxacin (n = 15) was used for
      definitive treatment of MRMP patients. Minocycline or DOX was significantly more
      effective than TFX (P <= .05) in achieving defervescence within 24 hours and in
      decreasing numbers of M. pneumoniae DNA copies 3 days after initiation.
      CONCLUSIONS: Macrolides are inappropriate as first-choice agents against MRMP in
      terms of shortening the clinical course and decreasing M. pneumoniae. Control and
      prevention of MRMP outbreaks in children require early decreases in M. pneumoniae
      as well as improvement of clinical findings.

PMID- 22972866
TI  - Clostridium difficile ribotype does not predict severe infection.
AB  - BACKGROUND: Studies of Clostridium difficile outbreaks suggested that certain
      ribotypes (eg, 027 and 078) cause more severe disease than other ribotypes. A
      growing number of studies challenge the validity of this hypothesis. METHODS: We
      conducted a cross-sectional study of C. difficile infection (CDI) to test whether
      ribotype predicted clinical severity when adjusted for the influence of other
      predictors. Toxigenic C. difficile isolates were cultured from stool samples,
      screened for genes encoding virulence factors by polymerase chain reaction (PCR)
      and ribotyped using high-throughput, fluorescent PCR ribotyping. We collected
      data for 15 covariates (microbiologic, epidemiologic, and laboratory variables)
      and determined their individual and cumulative influence on the association
      between C. difficile ribotype and severe disease. We then validated this
      influence using an independent data set. RESULTS: A total of 34 severe CDI cases
      were identified among 310 independent cases of disease (11.0%). Eleven
      covariates, including C. difficile ribotype, were significant predictors of
      severe CDI in unadjusted analysis. However, the association between ribotypes 027
      and 078 and severe CDI was not significant after adjustment for any of the other
      covariates. After full adjustment, severe cases were significantly predicted only
      by patients' white blood cell count and albumin level. This result was supported
      by analysis of a validation data set containing 433 independent CDI cases (45
      severe cases; 10.4%). CONCLUSIONS: Ribotype is not a significant predictor of
      severe CDI when adjusted for the influence of any other variables separately or
      in combination. White blood cell count and albumin level are the most clinically
      relevant predictors of severe CDI cases.

PMID- 22972859
TI  - Mortality in the year following antiretroviral therapy initiation in HIV-infected
      adults and children in Uganda and Zimbabwe.
AB  - BACKGROUND: Adult mortality in the first 3 months on antiretroviral therapy (ART)
      is higher in low-income than in high-income countries, with more similar
      mortality after 6 months. However, the specific patterns of changing risk and
      causes of death have rarely been investigated in adults, nor compared with
      children in low-income countries. METHODS: We used flexible parametric hazard
      models to investigate how mortality risks varied over the first year on ART in
      human immunodeficiency virus-infected adults (aged 18-73 years) and children
      (aged 4 months to 15 years) in 2 trials in Zimbabwe and Uganda. RESULTS: One
      hundred seventy-nine of 3316 (5.4%) adults and 39 of 1199 (3.3%) children died;
      half of adult/pediatric deaths occurred in the first 3 months. Mortality
      variation over year 1 was similar; at all CD4 counts/CD4%, mortality risk was
      greatest between days 30 and 50, declined rapidly to day 180, then declined more
      slowly. One-year mortality after initiating ART with 0-49, 50-99 or >= 100 CD4
      cells/MUL was 9.4%, 4.5%, and 2.9%, respectively, in adults, and 10.1%, 4.4%, and
      1.3%, respectively, in children aged 4-15 years. Mortality in children aged 4
      months to 3 years initiating ART in equivalent CD4% strata was also similar (0%
      4%: 9.1%; 5%-9%: 4.5%; >= 10%: 2.8%). Only 10 of 179 (6%) adult deaths and 1 of
      39 (3%) child deaths were probably medication-related. The most common cause of
      death was septicemia/meningitis in adults (20%, median 76 days) and children
      (36%, median 79 days); pneumonia also commonly caused child deaths (28%, median
      41 days). CONCLUSIONS: Children >= 4 years and adults with low CD4 values have
      remarkably similar, and high, mortality risks in the first 3 months after ART
      initiation in low-income countries, similar to cohorts of untreated individuals.
      Bacterial infections are a major cause of death in both adults and children;
      targeted interventions could have important benefits.

PMID- 22972870
TI  - Tigecycline and overall mortality.

PMID- 22972869
TI  - Vitamin D deficiency and its association with low bone mineral density, HIV
      related factors, hospitalization, and death in a predominantly black HIV-infected
      cohort.
AB  - BACKGROUND: Low bone mineral density (BMD) is common among patients infected with
      human immunodeficiency virus (HIV) and present in higher rates in black subjects.
      This study assessed vitamin D levels in HIV cases versus noninfected matched
      controls to determine if deficiency was associated with BMD and HIV clinical
      outcomes. METHODS: In total, 271 military beneficiaries with HIV underwent dual
      energy x-ray absorptiometry (DEXA) screening in 2001-2. Serum 25OH-vitamin D
      levels were determined using stored serum from the time of DEXA and 6-18 months
      prior. Two non-HIV-infected controls for each active duty case (n = 205) were
      matched on age, sex, race, zip code, and season using the Department of Defense
      Serum Repository (DoDSR). Vitamin D levels <20 ng/mL were considered deficient.
      HIV-related factors and clinical outcomes were assessed using data collected in
      the DoD HIV Natural History study. RESULTS: In total, 165 of 205 (80.5%) active
      duty HIV cases had 2 matched controls available. HIV cases had greater odds of
      for vitamin D deficiency (VDD) compared with controls (demographics adjusted
      paired data odds ratio [OR], 1.46, 95% confidence interval [CI], .87-2.45), but
      this was not statistically significant. Blacks were disproportionately deficient
      (P <.001) but not relative to HIV status or BMD. Low BMD was associated with
      typical risk factors (low body mass index and exercise levels, alcohol use);
      given limited available data the relationship between tenofovir exposure and VDD
      or low BMD could not be determined. Analysis of HIV-specific factors and outcomes
      such as exposure to antiretrovirals, HIV progression, hospitalizations, and death
      revealed no significant associations with vitamin D levels. CONCLUSIONS: VDD was
      highly prevalent in black HIV- infected persons but did not explain the observed
      racial disparity in BMD. Vitamin D deficiency was not more common among HIV-
      infected persons, nor did it seem associated with HIV- related factors/clinical
      outcomes.

PMID- 22972871
TI  - Effects of feedback-based visual line-orientation discrimination training for
      visuospatial disorders after stroke.
AB  - BACKGROUND: Patients with right or more rarely left parietotemporal lesions after
      stroke may have profound visuospatial disorders that impair activities of daily
      living (ADL) and long-term outcome. Clinical studies indicate improvements with
      systematic training of perception. Studies of perceptual learning in healthy
      persons suggest rapid improvements in perceptual learning of spatial line
      orientation with partial transfer to nontrained line orientations. OBJECTIVE: The
      authors investigated a novel feedback-based perceptual training procedure for the
      rehabilitation of patients after stroke. METHODS: In an uncontrolled trial, 13
      participants showing profound deficits in line orientation and related
      visuospatial tasks within 12 to 28 weeks of onset performed repetitive feedback
      based, computerized training of visual line orientation over 4 weeks of
      treatment. Visual line-orientation discrimination and visuospatial and
      visuoconstructive tasks were assessed before and after training. RESULTS: The
      authors found (a) rapid improvements in trained but also in nontrained spatial
      orientation tests in all 13 participants, partially up to a normal level; (b)
      stability of the obtained improvements at 2-month follow-up; (c) interocular
      transfer of training effects to the nontrained eye in 2 participants suggesting a
      central, postchiasmatic locus for this perceptual improvement; and (d) graded
      transfer of improvements to related spatial tasks, such as horizontal writing,
      analog clock reading, and visuoconstructive capacities but no transfer to
      unrelated measures of visual performance. CONCLUSIONS: These results suggest the
      potential for treatment-induced improvements in visuospatial deficits by feedback
      based, perceptual orientation training as a component of rehabilitation after
      stroke.

PMID- 22972872
TI  - Age-dependent effect of beta-blockers in preventing vasovagal syncope.
AB  - BACKGROUND: beta-blockers have little effectiveness in preventing vasovagal
      syncope in unselected populations, but they might be effective in older patients.
      We determined whether beta-blockers prevent vasovagal syncope in an age-related
      fashion. METHODS AND RESULTS: Two populations were studied. A proportional
      hazards analysis was performed on an observational cohort study of 153 patients
      with vasovagal syncope, 52 of whom received beta-blockers. A multivariable
      proportional hazards model stratified by center was performed on 208 participants
      in the randomized Prevention of Syncope Trial (POST), examining the interaction
      between age group and treatment with metoprolol. Age-specific hazard ratios were
      estimated for both studies and combined using the inverse variance meta-analytic
      method. In the cohort study, the hazard ratio for syncope if treated with beta
      blockers was 1.54 (95% CI, 0.78-3.05) for patients aged <42 years and 0.48 (95%
      CI, 0.12-1.92) for patients aged >= 42 years. In POST, the proportional hazards
      model showed interactions between age and treatment effect (P=0.026). The hazard
      ratio for patients aged >= 42 years who received metoprolol was 0.53 (95% CI,
      0.25-1.10); in patients aged <42 years, the hazard ratio was 1.62 (95% CI, 0.85
      3.10). A pooled analysis of both studies yielded an estimate of the hazard ratio
      of 1.58 (CI, 1.00-2.31) for patients aged <42 years, and the hazard ratio was
      0.52 (CI, 0.27-1.01) for patients aged >= 42 years. The 2 age groups differed
      significantly in response to beta-blockers (P=0.007). CONCLUSIONS: beta-blocker
      treatment may suppress vasovagal syncope in middle-aged patients aged >42 years.

PMID- 22972873
TI  - Single-ring posterior left atrial (box) isolation results in a different mode of
      recurrence compared with wide antral pulmonary vein isolation on long-term follow
      up: longer atrial fibrillation-free survival time but similar survival time free
      of any atrial arrhythmia.
AB  - BACKGROUND: Electric isolation of the pulmonary veins and posterior left atrium
      with a single ring of radiofrequency lesions (single-ring isolation [SRI]) may
      result in fewer atrial fibrillation (AF) recurrences than wide antral pulmonary
      vein isolation (wide antral isolation [WAI]) by abolishing extravenous AF
      triggers. The effect of mitral isthmus line (MIL) ablation on outcomes after SRI
      has not previously been assessed. METHODS AND RESULTS: We randomly assigned 220
      consecutive patients (58 +/- 10 years old; 82% men) with highly symptomatic AF
      (61% paroxysmal, 39% persistent/longstanding persistent) to undergo either SRI or
      WAI. Half of each cohort was also randomly allocated to have left lateral MIL
      ablation (2 *2 factorial study design). Patients were followed clinically and
      with 7-day Holter studies for arrhythmia recurrences. The primary end points were
      recurrence of AF and organized atrial tachyarrhythmias. AF-free survival at 2
      years was better after SRI (74% [95% CI, 65%-82%]) than WAI (61% [51%-70%];
      P=0.031). Organized atrial tachyarrhythmia-free survival was similar after SRI
      and WAI (67% [57%-75%] ersus 64% [54%-72%], respectively, at 2 years; P=0.988).
      MIL ablation resulted in better 2-year organized atrial tachyarrhythmia-free
      survival (71% [62%-79%] versus 60% [50%-69%]; P=0.07), which approached
      statistical significance. Survival free of any atrial arrhythmia after one
      procedure was not significantly affected by isolation technique or MIL ablation.
      Conclusions- SRI resulted in fewer AF recurrences compared with WAI on long-term
      follow-up but did not reduce the recurrence of all atrial arrhythmias. MIL
      ablation may reduce organized atrial tachyarrhythmia recurrences. Clinical Trial
      Registration- http://www.anzctr.org.au; ACTRN12606000467538.

PMID- 22972874
TI  - Validation of the Modified Brief Fatigue Inventory in head and neck cancer
      patients.
AB  - OBJECTIVE: The aim of this study is to validate the Modified Brief Fatigue
      Inventory (MBFI). This is the first instrument designed to measure intensity and
      frequency of fatigue specifically in head and neck cancer patients, potentially
      allowing objective measurement in addressing this common symptom in a concise yet
      thorough fashion. STUDY DESIGN: Survey validation. SETTING: Academic tertiary
      medical center. SUBJECTS AND METHODS: The 9-item MBFI was administered to 52
      consecutive cancer patients and 57 consecutive controls. Demographics,
      comorbidities, cancer site, and cancer stage were recorded. Psychometric
      properties and predictors of the MBFI were analyzed. RESULTS: The MBFI 1-week
      test-retest reliability was excellent (r = 0.800, P < .001). Internal consistency
      was also excellent (Cronbach's alpha = 0.938). Construct validity of the MBFI
      compared with the previously validated Multidimensional Fatigue Symptom Inventory
      Short Form was excellent (r = 0.814, P < .001). Discriminant validity of cancer
      patients vs controls was significant (P = .027). Predictors of increased MBFI
      score included American Society of Anesthesiologists (comorbidity) score
      (bivariate analysis, r = 0.287, P = .039), cancer stage (analysis of variance, P
      = .007), and adjuvant radiotherapy (t test, P = .016). Cancer stage and
      comorbidity were further correlated with a multiple regression linear model. No
      significant relationship was found with age, sex, marital status, education,
      ethnicity, feeding tube, tracheostomy, or laryngectomy. CONCLUSION: The MBFI is a
      reliable and valid tool for measuring fatigue levels in head and neck cancer
      patients. In the context of initial assessment or posttreatment trending, this
      brief survey can be rapidly administered, providing valuable objective data on a
      very common and potentially debilitating symptom.

PMID- 22972875
TI  - Mucin 5 subtype AC expression and upregulation in the nasal mucosa of allergic
      rhinitis rats.
AB  - OBJECTIVE: To elucidate the functions of nuclear factor kappa B (NF-kappaB) in
      mucin hypersecretion in allergic rhinitis (AR), we examined the in vivo effects
      of an NF-kappaB inhibitor, ammonium pyrrolidine dithiocarbamate (PDTC), on mucin
      5 subtype AC (MUC5AC) expression in the nasal mucosa of ovalbumin-sensitized
      rats. STUDY DESIGN: Randomized animal study. SETTING: Academic medical center.
      SUBJECTS AND METHODS: Sprague Dawley rats were randomized into a control group
      (group A), an AR model group (group B), and an AR model treated with an NF-kappaB
      inhibitor (group C). Rats in groups B and C were sensitized systemically and
      locally by ovalbumin injection and inhalation, whereas group A was treated with
      normal saline in place of ovalbumin. Pyrrolidine dithiocarbamate (100 mg/kg/d)
      was given to group C by intraperitoneal injection for 5 days. NF-kappaBp65,
      MUC5AC, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were detected
      by immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, or
      real-time polymerase chain reaction. RESULTS: NF-kappaB was activated in group B,
      and significant NF-kappaBp65 protein was expressed in the nucleus of cells from
      the nasal mucosa, resulting in upregulated transcription from TNF-alpha and IL-6
      genes, as well as increased contents of TNF-alpha and IL-6 in the nasal lavage
      fluids. Pyrrolidine dithiocarbamate inhibited nuclear localization of NF
      kappaBp65 and subsequent downregulation of the transcription and secretion of TNF
      alpha and IL-6. MUC5AC was upregulated in group B but reduced in a time-dependent
      manner after inhibition of NF-kappaB activation. CONCLUSION: NF-kappaB activation
      might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF-alpha
      and IL-6.

PMID- 22972876
TI  - Gene-targeted analysis of copy number variants identifies 3 novel associations
      with coronary heart disease traits.
AB  - BACKGROUND: Copy number variants (CNVs) are a major form of genomic variation,
      which may be implicated in complex disease phenotypes. However, investigation of
      the role of CNVs in coronary heart disease (CHD) traits has been limited. METHODS
      AND RESULTS: We examined the use of the cnvHap algorithm for CNV detection, using
      data for 2500 men from the Second Northwick Park Heart Study (NPHS-II). An
      Illumina custom chip, including 722 single-nucleotide polymorphisms covering 76
      coronary heart disease-trait genes, was used. Common CNVs were significantly
      associated (at P<0.05, after correction) with coronary heart disease phenotypes
      in 5 genes. Novel associations of CNVs in toll-like receptor-4 with
      apolipoprotein AI were replicated (P<0.05) in the Whitehall II cohort (4887
      subjects), whereas newly described associations of CNVs in sterol regulatory
      element-binding protein with apolipoprotein AI and associations of interleukin-6
      signal transducer with apolipoprotein B were replicated in the data from 3546
      subjects from the North Finnish Birth Cohort 1966 (P<0.05). CONCLUSIONS: This
      study supports the use of CNV detection algorithms such as cnvHap as potential
      tools for the identification of novel CNVs, some of which show significant
      association and replication with coronary heart disease risk phenotypes. However,
      the functional basis for these associations requires further substantiation.

PMID- 22972877
TI  - F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that
      regulates sarcomeric protein turnover and is essential for maintenance of
      contractile function in vivo.
AB  - RATIONALE: The emerging role of the ubiquitin-proteasome system in cardiomyocyte
      function and homeostasis implies the necessity of tight regulation of protein
      degradation. However, little is known about cardiac components of this machinery.
      OBJECTIVE: We sought to determine whether molecules exist that control turnover
      of cardiac-specific proteins. METHODS AND RESULTS: Using a bioinformatic approach
      to identify novel cardiac-enriched sarcomere proteins, we identified F-box and
      leucine-rich repeat protein 22 (Fbxl22). Tissue-specific expression was confirmed
      by multiple tissue Northern and Western Blot analyses as well as quantitative
      reverse-transcriptase polymerase chain reaction on a human cDNA library.
      Immunocolocalization experiments in neonatal and adult rat ventricular
      cardiomyocytes as well as murine heart tissue located Fbxl22 to the sarcomeric z
      disc. To detect cardiac protein interaction partners, we performed a yeast 2
      hybrid screen using Fbxl22 as bait. Coimmunoprecipitation confirmed the
      identified interactions of Fbxl22 with S-phase kinase-associated protein 1 and
      Cullin1, 2 critical components of SCF (Skp1/Cul1/F-box) E3- ligases. Moreover, we
      identified several potential substrates, including the z-disc proteins alpha
      actinin and filamin C. Consistently, in vitro overexpression of Fbxl22-mediated
      degradation of both substrates in a dose-dependent fashion, whereas proteasome
      inhibition with MG-132 markedly attenuated degradation of both alpha-actinin and
      filamin C. Finally, targeted knockdown of Fbxl22 in rat cardiomyocytes as well as
      zebrafish embryos results in the accumulation of alpha-actinin associated with
      severely impaired contractile function and cardiomyopathy in vivo. CONCLUSIONS:
      These findings reveal the previously uncharacterized cardiac-specific F-box
      protein Fbxl22 as a component of a novel cardiac E3 ligase. Fbxl22 promotes the
      proteasome-dependent degradation of key sarcomeric proteins, such as alpha
      actinin and filamin C, and is essential for maintenance of normal contractile
      function in vivo.

PMID- 22972878
TI  - Nutrition support of neonatal patients at risk for necrotizing enterocolitis:
      response to Fallon et al (2012).

PMID- 22972879
TI  - Perioperative oral administration of cystine and theanine enhances recovery after
      distal gastrectomy: a prospective randomized trial.
AB  - BACKGROUND: It has been reported that cystine and theanine, amino acids related
      to glutathione synthesis, have immunomodulatory effects, such as suppressing
      inflammation after strenuous exercise. In this study, we examined the effects of
      oral administration of cystine and theanine during the perioperative period as a
      pilot study. METHODS: Forty-three cases of distal gastrectomy for cancer
      conducted in our department were assigned to the cystine and theanine group (CT
      group) or to the placebo control group (P group), and a randomized, single-blind,
      parallel-group study was then performed. Cystine (700 mg) and theanine (280 mg)
      or a placebo was administered to participants for 10 continuous days (4 days
      before to 5 days after surgery). Changes in pre- and postoperative interleukin
      (IL)-6, C-reactive protein (CRP), albumin, white blood cell (WBC) count,
      neutrophil count, total lymphocyte count, resting energy expenditure (REE), and
      body temperature were compared and examined. RESULTS: Ten patients were excluded,
      leaving 33 patients in the study. The CT group had significantly lower IL-6
      values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD
      4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in
      the P group peaked on day 1 (1.14 +/- 0.16 [pre- and postoperative ratio]),
      whereas the CT group did not show any increase on POD 1 (0.99 +/- 0.21, P < .05
      vs P group). CONCLUSIONS: This study suggests that oral administration of cystine
      and theanine during the perioperative period may alleviate postgastrectomy
      inflammation and promote recovery after surgery.

PMID- 22972880
TI  - Symbiodinium isolation by NaOH treatment.
AB  - The presence of photosynthetic zooxanthellae (dinoflagellates) in the tissue of
      many cnidarians is the main reason for their ecological success (i.e. coral
      reefs). It could also be the main cause of their demise, as the worldwide
      bleaching of reef-building coral is nothing less than the breakdown of this
      symbiotic association. The stability of this relationship is the principal marker
      for the biomonitoring of cnidarian health. We have therefore developed a new,
      simple method to isolate zooxanthellae in a few steps using NaOH solution. The
      protocol was validated in three symbiotic cnidarian species: a sea anemone, a
      gorgonian and a coral. Our method allows the isolation of intact and viable
      zooxanthellae with better yields than classic methods, especially for species
      with a calcareous skeleton. Moreover, the isolated zooxanthellae were free of
      host nucleic contaminants, facilitating subsequent specific molecular analyses.

PMID- 22972881
TI  - Lipid composition of the stratum corneum and cutaneous water loss in birds along
      an aridity gradient.
AB  - Intercellular and covalently bound lipids within the stratum corneum (SC), the
      outermost layer of the epidermis, are the primary barrier to cutaneous water loss
      (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20
      species of birds from desert and mesic environments. Furthermore, we compared
      covalently bound lipids with CWL and intercellular lipids in the lark family
      (Alaudidae). We found that CWL increases in birds from more mesic environments,
      and this increase was related to changes in intercellular SC lipid composition.
      The most consistent pattern that emerged was a decrease in the relative amount of
      cerebrosides as CWL increased, a pattern that is counterintuitive based on
      studies of mammals with Gaucher disease. Although covalently bound lipids in
      larks did not correlate with CWL, we found that covalently bound cerebrosides
      correlated positively with intercellular cerebrosides and intercellular
      cholesterol ester, and intercellular cerebrosides correlated positively with
      covalently bound free fatty acids. Our results led us to propose a new model for
      the organization of lipids in the avian SC, in which the sugar moieties of
      cerebrosides lie outside of intercellular lipid layers, where they may
      interdigitate with adjacent intercellular cerebrosides or with covalently bound
      cerebrosides.

PMID- 22972882
TI  - Predictive saccade in the absence of smooth pursuit: interception of moving
      targets in the archer fish.
AB  - Interception of fast-moving targets is a demanding task many animals solve. To
      handle it successfully, mammals employ both saccadic and smooth pursuit eye
      movements in order to confine the target to their area centralis. But how can non
      mammalian vertebrates, which lack smooth pursuit, intercept moving targets? We
      studied this question by exploring eye movement strategies employed by archer
      fish, an animal that possesses an area centralis, lacks smooth pursuit eye
      movements, but can intercept moving targets by shooting jets of water at them. We
      tracked the gaze direction of fish during interception of moving targets and
      found that they employ saccadic eye movements based on prediction of target
      position when it is hit. The fish fixates on the target's initial position for
      ~0.2 s from the onset of its motion, a time period used to predict whether a shot
      can be made before the projection of the target exits the area centralis. If the
      prediction indicates otherwise, the fish performs a saccade that overshoots the
      center of gaze beyond the present target projection on the retina, such that
      after the saccade the moving target remains inside the area centralis long enough
      to prepare and perform a shot. These results add to the growing body of knowledge
      on biological target tracking and may shed light on the mechanism underlying this
      behavior in other animals with no neural system for the generation of smooth
      pursuit eye movements.

PMID- 22972883
TI  - Terrestrial locomotion imposes high metabolic requirements on bats.
AB  - The evolution of powered flight involved major morphological changes in
      Chiroptera. Nevertheless, all bats are also capable of crawling on the ground and
      some are even skilled sprinters. We asked if a highly derived morphology adapted
      for flapping flight imposes high metabolic requirements on bats when moving on
      the ground. We measured the metabolic rate during terrestrial locomotion in
      mastiff bats, Molossus currentium, a species that is both a fast-flying aerial
      hawking bat and an agile crawler on the ground. Metabolic rates of bats averaged
      8.0+/-4.0 ml CO(2) min(-1) during a 1-min period of sprinting at 1.3+/-0.6 km h(
      1). With rising average speed, mean metabolic rates increased, reaching peak
      values that were similar to those of flying conspecifics. Metabolic rates of M.
      currentium were higher than those of similar-sized rodents that sprinted at
      similar velocities under steady-state conditions. When M. currentium sprinted at
      peak velocities, its aerobic metabolic rate was 3-5 times higher than those of
      rodent species running continuously in steady-state conditions. Costs of
      transport (J kg(-1) m(-1)) were more than 10 times higher for running than for
      flying bats. We conclude that at the same speed bats experience higher metabolic
      rates during short sprints than quadruped mammals during steady-state terrestrial
      locomotion, yet running bats achieve higher maximal mass-specific aerobic
      metabolic rates than non-volant mammals such as rodents.

PMID- 22972884
TI  - Swimming away or clamming up: the use of phasic and tonic adductor muscles during
      escape responses varies with shell morphology in scallops.
AB  - The simple locomotor system of scallops facilitates the study of muscle use
      during locomotion. We compared five species of scallops with different shell
      morphologies to see whether shell morphology and muscle use change in parallel or
      whether muscle use can compensate for morphological constraints. Force recordings
      during escape responses revealed that the use of tonic and phasic contractions
      varied markedly among species. The active species, Amusium balloti, Placopecten
      magellanicus and Pecten fumatus, made more phasic contractions than the more
      sedentary species, Mimachlamys asperrima and Crassadoma gigantea. Tonic
      contractions varied considerably among these species, with the two more sedentary
      species often starting their response to the predator with a tonic contraction
      and the more active species using shorter tonic contractions between series of
      phasic contractions. Placopecten magellanicus made extensive use of short tonic
      contractions. Pecten fumatus mounted an intense series of phasic contractions at
      the start of its response, perhaps to overcome the constraints of its
      unfavourable shell morphology. Valve closure by the more sedentary species
      suggests that their shell morphology protects them against predation, whereas
      swimming by the more active species relies upon intense phasic contractions
      together with favourable shell characteristics.

PMID- 22972885
TI  - Muscle function during takeoff and landing flight in the pigeon (Columba livia).
AB  - This study explored the muscle strain and activation patterns of several key
      flight muscles of the pigeon (Columba livia) during takeoff and landing flight.
      Using electromyography (EMG) to measure muscle activation, and sonomicrometry to
      quantify muscle strain, we evaluated the muscle function patterns of the
      pectoralis, biceps, humerotriceps and scapulotriceps as pigeons flew between two
      perches. These recordings were analyzed in the context of three-dimensional wing
      kinematics. To understand the different requirements of takeoff, midflight and
      landing, we compared the activity and strain of these muscles among the three
      flight modes. The pectoralis and biceps exhibited greater fascicle strain rates
      during takeoff than during midflight or landing. However, the triceps muscles did
      not exhibit notable differences in strain among flight modes. All observed
      strain, activation and kinematics were consistent with hypothesized muscle
      functions. The biceps contracted to stabilize and flex the elbow during the
      downstroke. The humerotriceps contracted to extend the elbow at the upstroke
      downstroke transition, followed by scapulotriceps contraction to maintain elbow
      extension during the downstroke. The scapulotriceps also appeared to contribute
      to humeral elevation. Greater muscle activation intensity was observed during
      takeoff, compared with mid-flight and landing, in all muscles except the
      scapulotriceps. The timing patterns of muscle activation and length change
      differed among flight modes, yet demonstrated that pigeons do not change the
      basic mechanical actions of key flight muscles as they shift from flight
      activities that demand energy production, such as takeoff and midflight, to
      maneuvers that require absorption of energy, such as landing. Similarly, joint
      kinematics were consistent among flight modes. The stereotypy of these
      neuromuscular and joint kinematic patterns is consistent with previously observed
      stereotypy of wing kinematics relative to the pigeon's body (in the local body
      frame) across these flight behaviors. Taken together, these observations suggest
      that the control of takeoff and landing flight primarily involves modulation of
      overall body pitch to effect changes in stroke plane angle and resulting wing
      aerodynamics.

PMID- 22972886
TI  - MAPK phosphorylation is implicated in the adaptation to desiccation stress in
      nematodes.
AB  - Some nematodes can survive almost complete desiccation by entering an ametabolic
      state called anhydrobiosis requiring the accumulation of protective molecules
      such as trehalose and LEA proteins. However, it is not known how anhydrobiotic
      organisms sense and regulate the response to water loss. Mitogen-activated
      protein kinases (MAPKs) are highly conserved signalling proteins that regulate
      adaptation to various stresses. Here, we first compared the anhydrobiotic
      potential of three nematode species, Caenorhabditis elegans, Aphelenchus avenae
      and Panagrolaimus superbus, and then determined the phosphorylation status of the
      MAPKs p38, JNK and ERK during desiccation and rehydration. Caenorhabditis elegans
      was unable to undergo anhydrobiosis even after an initial phase of slow drying
      (preconditioning), while A. avenae did survive desiccation after preconditioning.
      In contrast, P. superbus withstood desiccation under rapid drying conditions,
      although survival rates improved with preconditioning. These results characterise
      C. elegans as desiccation sensitive, A. avenae as a slow desiccation strategist
      anhydrobiote and P. superbus as a fast desiccation strategist anhydrobiote. Both
      C. elegans and A. avenae showed increased MAPK phosphorylation during drying,
      consistent with an attempt to mount protection systems against desiccation
      stress. In P. superbus, however, MAPK phosphorylation was apparent prior to water
      loss and then decreased on dehydration, suggesting that signal transduction
      pathways are constitutively active in this nematode. Inhibition of p38 and JNK in
      P. superbus decreased its desiccation tolerance. This is consistent with the
      designation of P. superbus as a fast desiccation strategist and its high level of
      preparedness for anhydrobiosis in the hydrated state. These findings show that
      MAPKs play an important role in the survival of organisms during anhydrobiosis.

PMID- 22972887
TI  - Transition from leg to wing forces during take-off in birds.
AB  - Take-off mechanics are fundamental to the ecology and evolution of flying
      animals. Recent research has revealed that initial take-off velocity in birds is
      driven mostly by hindlimb forces. However, the contribution of the wings during
      the transition to air is unknown. To investigate this transition, we integrated
      measurements of both leg and wing forces during take-off and the first three
      wingbeats in zebra finch (Taeniopygia guttata, body mass 15 g, N=7) and diamond
      dove (Geopelia cuneata, body mass 50 g, N=3). We measured ground reaction forces
      produced by the hindlimbs using a perch mounted on a force plate, whole-body and
      wing kinematics using high-speed video, and aerodynamic forces using particle
      image velocimetry (PIV). Take-off performance was generally similar between
      species. When birds were perched, an acceleration peak produced by the legs
      contributed to 85+/-1% of the whole-body resultant acceleration in finch and 77+/
      6% in dove. At lift-off, coincident with the start of the first downstroke, the
      percentage of hindlimb contribution to initial flight velocity was 93.6+/-0.6% in
      finch and 95.2+/-0.4% in dove. In finch, the first wingbeat produced 57.9+/-3.4%
      of the lift created during subsequent wingbeats compared with 62.5+/-2.2% in
      dove. Advance ratios were <0.5 in both species, even when taking self-convection
      of shed vortices into account, so it was likely that wing-wake interactions
      dominated aerodynamics during wingbeats 2 and 3. These results underscore the
      relatively low contribution of the wings to initial take-off, and reveal a novel
      transitional role for the first wingbeat in terms of force production.

PMID- 22972888
TI  - Using the American alligator and a repeated-measures design to place constraints
      on in vivo shoulder joint range of motion in dinosaurs and other fossil
      archosaurs.
AB  - Using the extant phylogenetic bracket of dinosaurs (crocodylians and birds),
      recent work has reported that elbow joint range of motion (ROM) studies of fossil
      dinosaur forearms may be providing conservative underestimates of fully fleshed
      in vivo ROM. As humeral ROM occupies a more central role in forelimb movements,
      the placement of quantitative constraints on shoulder joint ROM could improve
      fossil reconstructions. Here, we investigated whether soft tissues affect the
      more mobile shoulder joint in the same manner in which they affect elbow joint
      ROM in an extant archosaur. This test involved separately and repeatedly
      measuring humeral ROM in Alligator mississippiensis as soft tissues were
      dissected away in stages to bare bone. Our data show that the ROMs of humeral
      flexion and extension, as well as abduction and adduction, both show a
      statistically significant increase as flesh is removed, but then decrease when
      the bones must be physically articulated and moved until they separate from one
      another and/or visible joint surfaces. A similar ROM pattern is inferred for
      humeral pronation and supination. All final skeletonized ROMs were less than
      initial fully fleshed ROMs. These results are consistent with previously reported
      elbow joint ROM patterns from the extant phylogenetic bracket of dinosaurs. Thus,
      studies that avoid separation of complementary articular surfaces may be
      providing fossil shoulder joint ROMs that underestimate in vivo ROM in dinosaurs,
      as well as other fossil archosaurs.

PMID- 22972889
TI  - What's hot: the enhancing effects of thermal stress on long-term memory formation
      in Lymnaea stagnalis.
AB  - The pond snail, Lymnaea stagnalis, naturally inhabits slow flowing, shallow and
      stagnant environments in the northern temperate zone. Consequently, it will
      experience wide temperature fluctuations dependent on prevailing weather
      conditions. We hypothesize that periods of warming act as a thermal stressor to
      alter memory formation. Snails were exposed to an acute 1 h period of 30 degrees
      C pond water and we determined how memory formation following operant
      conditioning of aerial respiration was affected. In the snails used here (Dutch
      strain), a single 0.5 h training session (TS) results in intermediate-term (3 h)
      but not long-term memory (LTM). Applying the thermal stressor during training
      caused memory enhancement (i.e. LTM lasting 24 h). However, the breathing rate
      also increased in warm water, which might explain the enhanced memory. Therefore,
      we applied the thermal stressor (1 h at 30 degrees C) up to 4 h before or 1 h
      after training. This did not alter baseline breathing rate during the period when
      snails would experience training. However, the thermal stressor whether
      experienced prior to or following the single TS, resulted in an enhanced memory
      that persisted up to 48h (i.e. LTM). We conclude that memory enhancement is due
      to the stress associated with the thermal stimulus.

PMID- 22972890
TI  - Limb force and non-sagittal plane joint moments during maximum-effort curve
      sprint running in humans.
AB  - Compared with running straight, when human runners sprint along a curve, the
      ability of the inside leg to generate force is compromised. This decreased force
      generation has been suggested to limit the overall performance of the runner. One
      theory for this force loss is that the large non-sagittal plane joint moments of
      the inside leg reach their operating limits, thus prohibiting further generation
      of the performance-related sagittal plane joint moments. We investigated the
      inside leg force generation and the ankle and knee joint moments when 13 subjects
      sprinted with and without an additional mass of 12.4 kg along a curve of 2.5 m
      radius. The increase in the subjects' mass evoked a significant increase in the
      resultant ground reaction force. The peak non-sagittal plane moments increased
      significantly for both the ankle and knee joints. This observation suggests that
      when sprinting normally with maximum effort, the non-sagittal plane joint moments
      are not operating at their limits. The large increases in ground reaction force
      were associated with greater extension moments generated at the knee joint. In
      contrast, the peak ankle plantarflexion moment remained unchanged across
      conditions. It is possible that for the specific joint configuration experienced,
      the overall ability to generate plantarflexion moment reaches the limit. Future
      studies with interventions increasing the ability of the muscle-tendon units to
      generate plantarflexion moment may provide an experimental opportunity to further
      examine this speculation.

PMID- 22972891
TI  - The impact of acute temperature stress on hemocytes of invasive and native
      mussels (Mytilus galloprovincialis and Mytilus californianus): DNA damage,
      membrane integrity, apoptosis and signaling pathways.
AB  - We investigated the effects of acute heat stress and cold stress on cell
      viability, lysosome membrane stability, double- and single-stranded DNA breakage,
      and signaling mechanisms involved in cellular homeostasis and apoptosis in
      hemocytes of native and invasive mussels, Mytilus californianus and Mytilus
      galloprovincialis, respectively. Both heat stress (28, 32 degrees C) and cold
      stress (2, 6 degrees C) led to significant double- and single-stranded breaks in
      DNA. The type and extent of DNA damage were temperature and time dependent, as
      was caspase-3 activation, an indicator of apoptosis, which may occur in response
      to DNA damage. Hemocyte viability and lysosomal membrane stability decreased
      significantly under heat stress. Western blot analyses of hemocyte extracts with
      antibodies for proteins associated with cell signaling and stress responses
      [including members of the phospho-specific mitogen-activated protein kinase
      (MAPK) family c-JUN NH(2)-terminal kinase (JNK) and p38-MAPK, and apoptosis
      executor caspase-3] revealed that heat and cold stress induced a time-dependent
      activation of JNK, p38-MAPK and caspase-3 and that these signaling and stress
      responses differed between species. The thermal limits for activation of cell
      signaling processes linked to the repair of stress-induced damage may help
      determine cellular thermal tolerance limits. Our results show similarities in
      responses to cold and heat stress and suggest causal linkages between levels of
      DNA damage at both extremes of temperature and downstream regulatory responses,
      including induction of apoptosis. Compared with M. californianus, M.
      galloprovincialis might have a wider temperature tolerance due to a lower amount
      of single- and double-stranded DNA damage, faster signaling activation and
      transduction, and stronger repair ability against temperature stress.

PMID- 22972892
TI  - Quadrupedal gaits in hexapod animals - inter-leg coordination in free-walking
      adult stick insects.
AB  - The analysis of inter-leg coordination in insect walking is generally a study of
      six-legged locomotion. For decades, the stick insect Carausius morosus has been
      instrumental for unravelling the rules and mechanisms that control leg
      coordination in hexapeds. We analysed inter-leg coordination in C. morosus that
      freely walked on straight paths on plane surfaces with different slopes.
      Consecutive 1.7 s sections were assigned inter-leg coordination patterns (which
      we call gaits) based on footfall patterns. Regular gaits, i.e. wave, tetrapod or
      tripod gaits, occurred in different proportions depending on surface slopes.
      Tetrapod gaits were observed most frequently, wave gaits only occurred on 90 deg
      inclining slopes and tripod gaits occurred most often on 15 deg declining slopes,
      i.e. in 40% of the sections. Depending on the slope, 36-66% of the sections were
      assigned irregular gaits. Irregular gaits were mostly due to multiple stepping by
      the front legs, which is perhaps probing behaviour, not phase coupled to the
      middle legs' cycles. In irregular gaits, middle leg and hindleg coordination was
      regular, related to quadrupedal walk and wave gaits. Apparently, front legs
      uncouple from and couple to the walking system without compromising middle leg
      and hindleg coordination. In front leg amputees, the remaining legs were strictly
      coordinated. In hindleg and middle leg amputees, the front legs continued
      multiple stepping. The coordination of middle leg amputees was maladapted, with
      front legs and hindlegs performing multiple steps or ipsilateral legs being in
      simultaneous swing. Thus, afferent information from middle legs might be
      necessary for a regular hindleg stepping pattern.

PMID- 22972894
TI  - The pro-apoptotic action of the peptide hormone Neb-colloostatin on insect
      haemocytes.
AB  - The gonadoinhibitory peptide hormone Neb-colloostatin was first isolated from
      ovaries of the flesh fly Neobellieria bullata. This 19-mer peptide is thought to
      be a cleaved product of a collagen-like precursor molecule that is formed during
      remodelling of the extracellular matrix. In this study, we report that upon
      injection of picomolar and nanomolar doses, this peptide exerts a pro-apoptotic
      action on haemocytes of Tenebrio molitor adults, as visualized by changes in
      morphology and viability. The F-actin cytoskeleton was found to aggregate into
      distinctive patches. This may be responsible for the observed inhibition of
      adhesion of haemocytes and for the stimulation of filopodia formation. However,
      Neb-colloostatin injection did not induce the formation of autophagic vacuoles.
      Our results suggest that physiological concentrations of Neb-colloostatin play an
      important role in controlling the quantity and activity of haemocytes in insect
      haemolymph. They also suggest that during periods in which Neb-colloostatin is
      released, this peptide may cause a weakening of the insects' immune system. This
      is the first report that exposure to a peptide hormone causes apoptosis in insect
      haemocytes.

PMID- 22972893
TI  - Recruitment of faster motor units is associated with greater rates of fascicle
      strain and rapid changes in muscle force during locomotion.
AB  - Animals modulate the power output needed for different locomotor tasks by
      changing muscle forces and fascicle strain rates. To generate the necessary
      forces, appropriate motor units must be recruited. Faster motor units have faster
      activation-deactivation rates than slower motor units, and they contract at
      higher strain rates; therefore, recruitment of faster motor units may be
      advantageous for tasks that involve rapid movements or high rates of work. This
      study identified motor unit recruitment patterns in the gastrocnemii muscles of
      goats and examined whether faster motor units are recruited when locomotor speed
      is increased. The study also examined whether locomotor tasks that elicit faster
      (or slower) motor units are associated with increased (or decreased) in vivo
      tendon forces, force rise and relaxation rates, fascicle strains and/or strain
      rates. Electromyography (EMG), sonomicrometry and muscle-tendon force data were
      collected from the lateral and medial gastrocnemius muscles of goats during level
      walking, trotting and galloping and during inclined walking and trotting. EMG
      signals were analyzed using wavelet and principal component analyses to quantify
      changes in the EMG frequency spectra across the different locomotor conditions.
      Fascicle strain and strain rate were calculated from the sonomicrometric data,
      and force rise and relaxation rates were determined from the tendon force data.
      The results of this study showed that faster motor units were recruited as goats
      increased their locomotor speeds from level walking to galloping. Slow inclined
      walking elicited EMG intensities similar to those of fast level galloping but
      different EMG frequency spectra, indicating that recruitment of the different
      motor unit types depended, in part, on characteristics of the task. For the
      locomotor tasks and muscles analyzed here, recruitment patterns were generally
      associated with in vivo fascicle strain rates, EMG intensity and tendon force.
      Together, these data provide new evidence that changes in motor unit recruitment
      have an underlying mechanical basis, at least for certain locomotor tasks.

PMID- 22972895
TI  - Lipid class and depth-specific thermal properties in the blubber of the short
      finned pilot whale and the pygmy sperm whale.
AB  - Blubber, the specialized hypodermis of cetaceans, provides thermal insulation
      through the quantity and quality of lipids it contains. Quality refers to percent
      lipid content; however, not all lipids are the same. Certain deep-diving cetacean
      groups possess blubber with lipids - wax esters (WE) - that are not typically
      found in mammals, and the insulative quality of 'waxy' blubber is unknown. Our
      study explored the influence of lipid storage class - specifically WE in pygmy
      sperm whales (Kogia breviceps; N=7) and typical mammalian triacylglycerols in
      short-finned pilot whales (Globicephala macrorhynchus; N=7) - on blubber's
      thermal properties. Although the blubber of both species had similar total lipid
      contents, the thermal conductivity of G. macrorhynchus blubber (0.20+/-0.01 W m(
      1)  degrees C(-1)) was significantly higher than that of K. breviceps (0.15+/
      0.01 W m(-1)  degrees C(-1); P=0.0006). These results suggest that lipid class
      significantly influences the ability of blubber to resist heat flow. In addition,
      because the lipid content of blubber is known to be stratified, we measured its
      depth-specific thermal conductivities. In K. breviceps blubber, the depth
      specific conductivity values tended to vary inversely with lipid content. In
      contrast, G. macrorhynchus blubber displayed unexpected depth-specific
      relationships between lipid content and conductivity, which suggests that
      temperature-dependent effects, such as melting, may be occurring. Differences in
      heat flux measurements across the depth of the blubber samples provide evidence
      that both species are capable of storing heat in their blubber. The function of
      blubber as an insulator is complex and may rely upon its lipid class, stratified
      composition and dynamic heat storage capabilities.

PMID- 22972896
TI  - Gestation increases the energetic cost of breathing in the lizard Tiliqua rugosa.
AB  - High gestational loads result in fetuses that occupy a large proportion of the
      body cavity and may compress maternal organs. Compression of the lungs results in
      alterations in breathing patterns during gestation, which may affect the
      energetic cost of breathing. In this study, the energetic cost of breathing
      during gestation was determined in the viviparous skink Tiliqua rugosa.
      Radiographic imaging showed progressive lung compression during gestation and a
      30% reduction in the lung inflation index (rib number at which the caudal margin
      of the lung was imaged divided by total rib number). Pneumotachography and open
      flow respirometry were used to measure breathing patterns and metabolic rates.
      Gestation induced a twofold increase in minute ventilation via increases in
      breathing frequency, but no change in inspired tidal volume. The rates of O(2)
      consumption and CO(2) production did not change significantly during gestation.
      Together, these results suggest that a relative hyperventilation occurs during
      gestation in T. rugosa, which in turn suggests that diffusion and/or perfusion
      limitations may exist at the lung during gestation. The energetic cost of
      breathing was estimated as a percentage of resting metabolic rate using
      hypercapnia to stimulate ventilation at different stages of pregnancy. The
      energetic cost of breathing in non-pregnant lizards was 19.96+/-3.85% of resting
      metabolic rate and increased threefold to 62.80+/-10.11% during late gestation.
      This significant increase in the energetic cost of breathing may have significant
      consequences for energy budgets during gestation.

PMID- 22972897
TI  - Ant foraging on complex trails: route learning and the role of trail pheromones
      in Lasius niger.
AB  - Ants are central place foragers and use multiple information sources to navigate
      between the nest and feeding sites. Individual ants rapidly learn a route, and
      often prioritize memory over pheromone trails when tested on a simple trail with
      a single bifurcation. However, in nature, ants often forage at locations that are
      reached via more complex routes with multiple trail bifurcations. Such routes may
      be more difficult to learn, and thus ants would benefit from additional
      information. We hypothesized that trail pheromones play a more significant role
      in ant foraging on complex routes, either by assisting in navigation or route
      learning or both. We studied Lasius niger workers foraging on a doubly
      bifurcating trail with four end points. Route learning was slower and errors
      greater on alternating (e.g. left-right) versus repeating routes (e.g. left
      left), with error rates of 32 and 3%, respectively. However, errors on
      alternating routes decreased by 30% when trail pheromone was present. Trail
      pheromones also aid route learning, leading to reduced errors in subsequent
      journeys without pheromone. If an experienced forager makes an error when
      returning to a food source, it reacts by increasing pheromone deposition on the
      return journey. In addition, high levels of trail pheromone suppress further
      pheromone deposition. This negative feedback mechanism may act to conserve
      pheromone or to regulate recruitment. Taken together, these results demonstrate
      further complexity and sophistication in the foraging system of ant colonies,
      especially in the role of trail pheromones and their relationship with learning
      and the use of private information (memory) in a complex environment.

PMID- 22972898
TI  - The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat
      tailed dunnart.
AB  - At birth, the newborn fat-tailed dunnart relies on cutaneous gas exchange to meet
      metabolic demands, with continuous lung ventilation emerging several days later.
      We hypothesised that the delayed expression of lung ventilation (V(E)) in these
      animals is in part due to a low responsiveness of the respiratory control system
      to blood gas perturbations. To address this hypothesis, we assessed the
      ventilatory and metabolic response to hypoxia (10% O(2)) and hypercapnia (5%
      CO(2)) using closed-system respirometry from birth to 23 days postpartum (P).
      Neonatal fat-tailed dunnarts displayed no significant hypoxic or hypercapnic
      ventilatory responses at any age. Regardless, significant hyperventilation
      through a suppression of metabolic rate (V(O(2))) was observed at birth in
      response to hypercapnia and in response to hypoxia at all ages, except P12.
      Therefore, reliance on cutaneous gas exchange during early life may be partially
      attributed to reduced chemosensitivity or a lack of central integration of
      chemosensitive afferent information. This may be in part due to the relative
      immaturity of this species at birth, compared with other mammals.

PMID- 22972899
TI  - Ovarian developmental variation in the primitively eusocial wasp Ropalidia
      marginata suggests a gateway to worker ontogeny and the evolution of sociality.
AB  - Social insects are characterized by reproductive caste differentiation of colony
      members into one or a small number of fertile queens and a large number of
      sterile workers. The evolutionary origin and maintenance of such sterile workers
      remains an enduring puzzle in insect sociobiology. Here, we studied ovarian
      development in over 600 freshly eclosed, isolated, virgin female Ropalidia
      marginata wasps, maintained in the laboratory. The wasps differed greatly both in
      the time taken to develop their ovaries and in the magnitude of ovarian
      development despite having similar access to resources. All females started with
      no ovarian development at day zero, and the percentage of individuals with at
      least one oocyte at any stage of development increased gradually across age,
      reached 100% at 100 days and decreased slightly thereafter. Approximately 40% of
      the females failed to develop ovaries within the average ecological lifespan of
      the species. Age, body size and adult feeding rate, when considered together,
      were the most important factors governing ovarian development. We suggest that
      such flexibility and variation in the potential and timing of reproductive
      development may physiologically predispose females to accept worker roles and
      thus provide a gateway to worker ontogeny and the evolution of sociality.

PMID- 22972901
TI  - Targeted proteomics for determining phosphorylation site-specific associations in
      cardiovascular disease.

PMID- 22972900
TI  - Multiple reaction monitoring to identify site-specific troponin I phosphorylated
      residues in the failing human heart.
AB  - BACKGROUND: Human cardiac troponin I is known to be phosphorylated at multiple
      amino acid residues by several kinases. Advances in mass spectrometry allow
      sensitive detection of known and novel phosphorylation sites and measurement of
      the level of phosphorylation simultaneously at each site in myocardial samples.
      METHODS AND RESULTS: On the basis of in silico prediction and liquid
      chromatography/mass spectrometry data, 14 phosphorylation sites on cardiac
      troponin I, including 6 novel residues (S4, S5, Y25, T50, T180, S198), were
      assessed in explanted hearts from end-stage heart failure transplantation
      patients with ischemic heart disease or idiopathic dilated cardiomyopathy and
      compared with samples obtained from nonfailing donor hearts (n=10 per group).
      Thirty mass spectrometry-based multiple reaction monitoring quantitative tryptic
      peptide assays were developed for each phosphorylatable and corresponding
      nonphosphorylated site. The results show that in heart failure there is a
      decrease in the extent of phosphorylation of the known protein kinase A sites
      (S22, S23) and other newly discovered phosphorylation sites located in the N
      terminal extension of cardiac troponin I (S4, S5, Y25), an increase in
      phosphorylation of the protein kinase C sites (S41, S43, T142), and an increase
      in phosphorylation of the IT-arm domain residues (S76, T77) and C-terminal domain
      novel phosphorylation sites of cardiac troponin I (S165, T180, S198). In a canine
      dyssynchronous heart failure model, enhanced phosphorylation at 3 novel sites was
      found to decline toward control after resynchronization therapy. CONCLUSIONS:
      Selective, functionally significant phosphorylation alterations occurred on
      individual residues of cardiac troponin I in heart failure, likely reflecting an
      imbalance in kinase/phosphatase activity. Such changes can be reversed by cardiac
      resynchronization.

PMID- 22972902
TI  - G(13)-mediated signaling pathway is required for pressure overload-induced
      cardiac remodeling and heart failure.
AB  - BACKGROUND: Cardiac remodeling in response to pressure or volume overload plays
      an important role in the pathogenesis of heart failure. Various mechanisms have
      been suggested to translate mechanical stress into structural changes, one of
      them being the release of humoral factors such as angiotensin II and endothelin
      1, which in turn promote cardiac hypertrophy and fibrosis. A large body of
      evidence suggests that the prohypertrophic effects of these factors are mediated
      by receptors coupled to the G(q/11) family of heterotrimeric G proteins. Most
      G(q/11)-coupled receptors, however, can also activate G proteins of the G(12/13)
      family, but the role of G(12/13) in cardiac remodeling is not understood. METHODS
      AND RESULTS: We use siRNA-mediated knockdown in vitro and conditional gene
      inactivation in vivo to study  the role of the G(12/13) family in pressure
      overload-induced cardiac remodeling. We show in detail that inducible
      cardiomyocyte-specific inactivation of the alpha subunit of G(13), Galpha(13),
      does not affect basal heart function but protects mice from pressure overload
      induced hypertrophy and fibrosis as efficiently as inactivation of Galpha(q/11).
      Furthermore, inactivation of Galpha(13) prevents the development of heart failure
      up to 1 year after overloading. On the molecular level, we show that Galpha(13),
      but not Galpha(q/11), controls agonist-induced expression of hypertrophy-specific
      genes through activation of the small GTPase RhoA and consecutive activation of
      myocardin-related transcription factors. CONCLUSION: Our data show that the
      G(12/13) family of heterotrimeric G proteins is centrally involved in pressure
      overload-induced cardiac remodeling and plays a central role in the transition to
      heart failure.

PMID- 22972903
TI  - Modifying the classroom environment to increase engagement and decrease
      disruption with students who are deaf or hard of hearing.
AB  - The goal of this study was to examine the effect of physical modifications on the
      academic engagement and disruptive behavior of Deaf or Hard-of-Hearing students
      in self-contained classrooms. Three classrooms at a school for the Deaf were
      modified after consultation with the classroom teachers. The modifications of the
      classroom environment included changes in seating arrangements, classroom
      organization, visual stimulation, and acoustic quality. A multiple-baseline
      design was used to examine the effects of the intervention on the frequency of
      student academic engagement and disruptive behaviors. Results show a functional
      relationship between the physical environment and both an increase in levels of
      academic engagement and a decrease in levels of disruptive behavior. Teachers
      maintained the majority of modifications after the study ceased. Social validity
      ratings by the teachers indicated high acceptability of the intervention.
      Limitations and practical implications for future research are discussed.

PMID- 22972904
TI  - Honesty requires time (and lack of justifications).
AB  - Recent research suggests that refraining from cheating in tempting situations
      requires self-control, which indicates that serving self-interest is an automatic
      tendency. However, evidence also suggests that people cheat to the extent that
      they can justify their unethical behavior to themselves. To merge these different
      lines of research, we adopted a dual-system approach that distinguished between
      the intuitive and deliberative cognitive systems. We suggest that for people to
      restrict their dishonest behavior, they need to have enough time and no
      justifications for self-serving unethical behavior. We employed an anonymous die
      under-cup task in which participants privately rolled a die and reported the
      outcome to determine their pay. We manipulated the time available for
      participants to report their outcome (short vs. ample). The results of two
      experiments support our prediction, revealing that the dark side of people's
      automatic self-serving tendency may be overcome when time to decide is ample and
      private justifications for dishonesty are not available.

PMID- 22972905
TI  - Giving time gives you time.
AB  - Results of four experiments reveal a counterintuitive solution to the common
      problem of feeling that one does not have enough time: Give some of it away.
      Although the objective amount of time people have cannot be increased (there are
      only 24 hours in a day), this research demonstrates that people's subjective
      sense of time affluence can be increased. We compared spending time on other
      people with wasting time, spending time on oneself, and even gaining a windfall
      of "free" time, and we found that spending time on others increases one's feeling
      of time affluence. The impact of giving time on feelings of time affluence is
      driven by a boosted sense of self-efficacy. Consequently, giving time makes
      people more willing to commit to future engagements despite their busy schedules.

PMID- 22972906
TI  - Memory and cognitive control in task switching.
AB  - Cognitive control and memory are fundamentally intertwined, but interactions
      between the two have only recently received sustained research interest. In the
      study reported here, we used a novel paradigm to investigate how control
      influences memory encoding and, conversely, how memory measures can provide new
      insight into flexible cognitive control. Participants switched between
      classifying objects and words, then were tested for their recognition memory of
      items presented in this task-switching phase. Task switching impaired memory for
      task-relevant information but actually improved memory for task-irrelevant
      information, which indicates that control demands reduced the selectivity of
      memory encoding rather than causing a general memory decline. Recognition memory
      strength provided a robust trial-by-trial measure of the effectiveness of
      cognitive control that "predicted" earlier task-switching performance. It also
      revealed a substantial influence of bottom-up factors on between-task
      competition, but only on trials in which participants had to switch from one type
      of classification to the other. Collectively, our findings illustrate how
      cognitive control and bottom-up factors interact to simultaneously influence both
      current performance and future memory.

PMID- 22972907
TI  - Motivational versus metabolic effects of carbohydrates on self-control.
AB  - Self-control is critical for achievement and well-being. However, people's
      capacity for self-control is limited and becomes depleted through use. One
      prominent explanation for this depletion posits that self-control consumes energy
      through carbohydrate metabolization, which further suggests that ingesting
      carbohydrates improves self-control. Some evidence has supported this energy
      model, but because of its broad implications for efforts to improve self-control,
      we reevaluated the role of carbohydrates in self-control processes. In four
      experiments, we found that (a) exerting self-control did not increase
      carbohydrate metabolization, as assessed with highly precise measurements of
      blood glucose levels under carefully standardized conditions; (b) rinsing one's
      mouth with, but not ingesting, carbohydrate solutions immediately bolstered self
      control; and (c) carbohydrate rinsing did not increase blood glucose. These
      findings challenge metabolic explanations for the role of carbohydrates in self
      control depletion; we therefore propose an alternative motivational model for
      these and other previously observed effects of carbohydrates on self-control.

PMID- 22972908
TI  - "The mind is willing, but the flesh is weak": the effects of mind-body dualism on
      health behavior.
AB  - Beliefs in mind-body dualism--that is, perceiving one's mind and body as two
      distinct entities--are evident in virtually all human cultures. Despite their
      prevalence, surprisingly little is known about the psychological implications of
      holding such beliefs. In the research reported here, we investigated the
      relationship between dualistic beliefs and health behaviors. We theorized that
      holding dualistic beliefs leads people to perceive their body as a mere "shell"
      and, thus, to neglect it. Supporting this hypothesis, our results showed that
      participants who were primed with dualism reported less engagement in healthy
      behaviors and less positive attitudes toward such behaviors than did participants
      primed with physicalism. Additionally, we investigated the bidirectionality of
      this link. Activating health-related concepts affected participants' subsequently
      reported metaphysical beliefs in mind-body dualism. A final set of studies
      demonstrated that participants primed with dualism make real-life decisions that
      may ultimately compromise their physical health (e.g., consuming unhealthy food).
      These findings have potential implications for health interventions.

PMID- 22972909
TI  - Pharmacokinetics of pegylated liposomal doxorubicin administered by
      intraoperative hyperthermic intraperitoneal chemotherapy to patients with
      advanced ovarian cancer and peritoneal carcinomatosis.
AB  - The pharmacokinetics of pegylated liposomal doxorubicin (PLD) were investigated
      in 17 women undergoing intraoperative hyperthermic intraperitoneal chemotherapy
      (HIPEC) for advanced ovarian cancer and peritoneal carcinomatosis. HIPEC was
      performed immediately after completing debulking surgery, which included a number
      of peritonectomy procedures. PLD was injected and allowed to equilibrate in
      peritoneal cavity filled with 4 liters of physiological solution and stabilized
      at 42 degrees C; next, the outflow line was opened and perfusion proceeded for 1
      h. PLD was stable in peritoneal perfusate and plasma. During HIPEC, PLD
      peritoneal perfusate/plasma gradients averaged ~600 or >=1000 for peak
      concentration or area under the curve. After HIPEC, PLD plasma levels remained
      stable or decreased. Biopsy samples of residual normal peritoneum or ovarian
      carcinomatosis were collected at the end of HIPEC and were shown to contain free
      doxorubicin. Correlating PLD decrements in peritoneal perfusate with plasma
      exposure to PLD or peritoneal deposition of free doxorubicin showed that the
      former occurred during preperfusional equilibration of PLD in peritoneal cavity,
      whereas the latter occurred during 1 h of perfusion. Plasma exposure to PLD
      correlated negatively with the number of peritonectomy procedures performed
      during surgery, whereas peritoneal deposition of free doxorubicin correlated
      positively. Taken together, these results show that PLD administered by
      intraoperative HIPEC undergoes limited systemic diffusion and releases active
      free doxorubicin in peritoneum exposed to ovarian carcinomatosis. PLD
      pharmacokinetics seem to be influenced by peritonectomy procedures.

PMID- 22972910
TI  - IGF receptor gene variants in normal adolescents: effect on stature.
AB  - OBJECTIVE: IGF1 is essential for human growth and mediates its effects through
      the type 1 IGF receptor (IGF1R). Our objective was to determine the frequency of
      certain previously reported IGF1R gene variants in the normal population and
      their effect on stature. DESIGN: A cross-sectional study was conducted in a
      population of 2500 children enrolled in public school grades 5 through 12 for
      whom DNA and anthropometric data were available. Subjects were genotyped at five
      previously reported loci that affect receptor abundance or function. METHODS: The
      frequency of the following IGF1R variants Arg108Gln, Lys115Asn, Arg59stop,
      Arg481Gln, and Arg605His was measured by a PCR-based assay. Circulating
      concentrations of IGF1 or IGF binding protein-3 (IGFBP3) were measured by ELISA
      in those affected and matched controls. RESULTS: A scan of 1300 subjects detected
      none with Arg108Gln, Lys115Asn, or Arg59stop mutations. In contrast, nucleotide
      changes leading to heterozygosity at codon 605 were identified in nine of 2500
      subjects and six of 1800 subjects at codon 481. These individuals were, on
      average, 4 cm shorter than the others. There were no differences in circulating
      concentrations of IGF1 or IGFBP3 between those with the gene variants and
      controls matched for sex, ethnicity, age, and BMI. CONCLUSION: Rare IGF1R
      variants exerting a moderate effect on stature are present in the general
      population, supporting the importance of IGF1R function in growth control and
      indicating that variation in height within healthy individuals may be explained,
      in some cases, by larger effects of a small subset of gene variants.

PMID- 22972911
TI  - Echocardiographic-based assessment of myocardial fiber structure in individual,
      excised hearts.
AB  - The objective of this study was to assess the feasibility of using
      echocardiographic imaging as an approach for determining the myocardial fiber
      structure of intact, individual hearts. Seven formalin-fixed, ex vivo sheep
      hearts were imaged using a commercially available echocardiographic imaging
      system, and the intrinsic fiber structure for the reconstructed short-axis cross
      section was determined for a specific distance from the apex of each heart.
      Diffusion tensor magnetic resonance (DT-MR) images of each heart were acquired
      and fiber maps were created for comparison with the fiber structure obtained from
      the corresponding reconstructed echocardiographic images. These two methods of
      obtaining the fiber structure showed relatively good agreement, suggesting that
      measurements of fiber orientation for individual hearts can be derived from
      echocardiographic images. Further development of this method may provide a
      clinically useful approach for mapping the fiber orientation in individual
      patients over the heart cycle.

PMID- 22972912
TI  - Acoustic radiation force impulse imaging of mechanical stiffness propagation in
      myocardial tissue.
AB  - Acoustic radiation force impulse (ARFI) imaging has been shown to be capable of
      imaging local myocardial stiffness changes throughout the cardiac cycle.
      Expanding on these results, the authors present experiments using cardiac ARFI
      imaging to visualize and quantify the propagation of mechanical stiffness during
      ventricular systole. In vivo ARFI images of the left ventricular free wall of two
      exposed canine hearts were acquired. Images were formed while the heart was
      externally paced by one of two electrodes positioned on the epicardial surface
      and either side of the imaging plane. Two-line M-mode ARFI images were acquired
      at a sampling frequency of 120 Hz while the heart was paced from an external
      stimulating electrode. Two-dimensional ARFI images were also acquired, and an
      average propagation velocity across the lateral field of view was calculated.
      Directions and speeds of myocardial stiffness propagation were measured and
      compared with the propagations derived from the local electrocardiogram (ECG),
      strain, and tissue velocity measurements estimated during systole. In all ARFI
      images, the direction of myocardial stiffness propagation was seen to be away
      from the stimulating electrode and occurred with similar velocity magnitudes in
      either direction. When compared with the local epicardial ECG, the mechanical
      stiffness waves were observed to travel in the same direction as the propagating
      electrical wave and with similar propagation velocities. In a comparison between
      ARFI, strain, and tissue velocity imaging, the three methods also yielded similar
      propagation velocities.

PMID- 22972913
TI  - A method for direct localized sound speed estimates using registered virtual
      detectors.
AB  - Accurate sound speed estimates are desirable in a number of fields. In an effort
      to increase the spatial resolution of sound speed estimates, a new method is
      proposed for direct measurement of sound speed between arbitrary spatial
      locations. The method uses the sound speed estimator developed by Anderson and
      Trahey. Their least squares fit of the received waveform's curvature provides an
      estimate of the wave's point of origin. The point of origin and the delay profile
      calculated from the fit are used to arrive at a spatially registered virtual
      detector. Between a pair of registered virtual detectors, a spherical wave is
      propagated. By beamforming the data, the time-of-flight between the two virtual
      sources can be calculated. From this information, the local sound speed can be
      estimated. Validation of the estimator is made using phantom and simulation data.
      The set of test phantoms consisted of both homogeneous and inhomogeneous media.
      Several different inhomogeneous phantom configurations were used for the physical
      validation. The simulation validation focused on the limits of target depth and
      signal-to-noise ratio on virtual detector registration. The simulations also
      compare the impact of two- and three-layer inhomogeneous media. The phantom
      results varied based on signal-to-noise ratio and geometry. The results for all
      cases were generally less than 1% mean error and standard deviation. The
      simulation results varied somewhat with depth and F/#, but primarily, they varied
      with signal-to-noise ratio and geometry. With two-layer geometries, the algorithm
      has a worst-case spatial registration bias of 0.02%. With three-layer geometries,
      the axial registration error gets worse with a bias magnitude up to 2.1% but is
      otherwise relatively stable over depth. The stability over depth of the bias in a
      given medium still allows for accurate sound speed estimates with a mean relative
      error less than 0.2%.

PMID- 22972914
TI  - A 5-MHz cylindrical dual-layer transducer array for 3-D transrectal ultrasound
      imaging.
AB  - Two-dimensional transrectal ultrasound (TRUS) is being used in guiding prostate
      biopsies and treatments. In many cases, the TRUS probes are moved manually or
      mechanically to acquire volumetric information, making the imaging slow, user
      dependent, and unreliable. A real-time three-dimensional (3-D) TRUS system could
      improve reliability and volume rates of imaging during these procedures. In this
      article, the authors present a 5-MHz cylindrical dual-layer transducer array
      capable of real-time 3-D transrectal ultrasound without any mechanically moving
      parts. Compared with fully sampled 2-D arrays, this design substantially reduces
      the channel count and fabrication complexity. This dual-layer transducer uses PZT
      elements for transmit and P[VDF-TrFE] copolymer elements for receive,
      respectively. The mechanical flexibility of both diced PZT and copolymer makes it
      practical for transrectal applications. Full synthetic aperture 3-D data sets
      were acquired by interfacing the transducer with a Verasonics Data Acquisition
      System. Offline 3-D beamforming was then performed to obtain volumes of two wire
      phantoms and a cyst phantom. Generalized coherence factor was applied to improve
      the contrast of images. The measured -6-dB fractional bandwidth of the transducer
      was 62% with a center frequency of 5.66 MHz. The measured lateral beamwidths were
      1.28 mm and 0.91 mm in transverse and longitudinal directions, respectively,
      compared with a simulated beamwidth of 0.92 mm and 0.74 mm.

PMID- 22972915
TI  - High-frequency annular array fabrication using a flex circuit matching layer.
AB  - Fabricating arrays for high-frequency image applications such as ophthalmic
      imaging, intravascular imaging, and small animal imaging is challenging. For
      example, an array for intravascular imaging must be small enough to fit within
      the lumen of a catheter and inexpensive enough to be discarded after a single
      use. This article presents a new method for fabricating high-frequency annular
      arrays that is simple and inexpensive. The annular array elements are defined by
      the electrode pattern on a back surface of a polyimide quarter-wavelength
      matching layer that is glued to the front face of a ceramic transducer substrate
      (PZT5H). Electrical losses associated with bonding the matching layer to the
      transducer substrate are reduced by fabricating a second set of electrodes on the
      transducer substrate and then bonding the substrates using an anisotropic
      conductive epoxy. The feasibility of this technique was established by
      fabricating a seven-element, 20-MHz, 5-mm diameter annular array. The prototype
      array produced a pulse with a -6-dB factional bandwidth of 50%, an insertion loss
      of 22 dB, and secondary lobes in the radiation pattern at f/2 that decreased to 
      65 dB with respect to the main lobe with a peak amplitude of -53 dB.

PMID- 22972916
TI  - Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation
      and neointimal formation.
AB  - Obesity is closely associated with the progression of vascular disorders,
      including atherosclerosis and postangioplasty restenosis. C1q/TNF-related protein
      (CTRP) 9 is an adipocytokine that is down-regulated in obese mice. Here we
      investigated whether CTRP9 modulates neointimal hyperplasia and vascular smooth
      muscle cell (VSMC) proliferation in vivo and in vitro. Left femoral arteries of
      wild-type (WT) mice were injured by a steel wire. An adenoviral vector expressing
      CTRP9 (Ad-CTRP9) or beta-galactosidase as a control was intravenously injected
      into WT mice 3 d before vascular injury. Delivery of Ad-CTRP9 significantly
      attenuated the neointimal thickening and the number of bromodeoxyuridine-positive
      proliferating cells in the injured arteries compared with that of control.
      Treatment of VSMCs with CTRP9 protein attenuated the proliferative and
      chemotactic activities induced by growth factors including platelet-derived
      growth factor (PDGF)-BB, and suppressed PDGF-BB-stimulated phosphorylation of
      ERK. CTRP9 treatment dose-dependently increased cAMP levels in VSMCs. Blockade of
      cAMP-PKA pathway reversed the inhibitory effect of CTRP9 on DNA synthesis and ERK
      phosphorylation in response to PDGF-BB. The present data indicate that CTRP9
      functions to attenuate neointimal formation following vascular injury through its
      ability to inhibit VSMC growth via cAMP-dependent mechanism, suggesting that the
      therapeutic approaches to enhance CTRP9 production could be valuable for
      prevention of vascular restenosis after angioplasty.

PMID- 22972918
TI  - Distinct energy requirements for human memory CD4 T-cell homeostatic functions.
AB  - Differentiation and activation of CD4 memory T cells (T(mem) cells) require
      energy from different sources, but little is known about energy sources for
      maintenance and surveillance activities of unactivated T(mem) cells.
      Mitochondrial fatty acid oxidation (FAO) in human unactivated CD4 T(mem) cells
      was significantly enhanced by inhibition of glycolysis, with respective means of
      1.7- and 4.5-fold for subjects <45 yr and >65 yr, and by stimulation of AMP
      activated protein kinase, with respective means of 1.3- and 5.2-fold. However,
      CCL19 and sphingosine 1-phosphate (S1P), which control homeostatic lymphoid
      trafficking of unactivated T(mem) cells, altered FAO and glycolysis only
      minimally or not at all. Inhibition of CD4 T(mem)-cell basal FAO, but not basal
      glycolysis, significantly suppressed CCL19- and S1P-mediated adherence to
      collagen by >50 and 20%, respectively, and chemotaxis by >20 and 50%. Apoptosis
      of unactivated T(mem) cells induced by IL-2 deprivation or CCL19 was increased
      significantly by >150 and 70%, respectively, with inhibition of FAO and by >110
      and 30% with inhibition of glycolysis. Anti-TCR antibody activation of T(mem)
      cells increased their chemotaxis to CCL5, which was dependent predominantly on
      glycolysis rather than FAO. The sources supplying energy for diverse functions of
      unactivated T(mem) cells differ from that required for function after immune
      activation.

PMID- 22972917
TI  - Small-molecule inducers of Abeta-42 peptide production share a common mechanism
      of action.
AB  - The pathways leading specifically to the toxic Abeta42 peptide production, a key
      event in Alzheimer's disease (AD), are unknown. While searching for pathways that
      mediate pathological increases of Abeta42, we identified Aftin-4, a new compound
      that selectively and potently increases Abeta42 compared to DMSO (N2a cells: 7
      fold; primary neurons: 4-fold; brain lysates: 2-fold) with an EC(50) of 30 MUM.
      These results were confirmed by ELISA and IP-WB. Using affinity chromatography
      and mass spectrometry, we identified 3 proteins (VDAC1, prohibitin, and
      mitofilin) relevant to AD that interact with Aftin-4, but not with a structurally
      similar but inactive molecule. Electron microscopy studies demonstrated that
      Aftin-4 induces a reversible mitochondrial phenotype reminiscent of the one
      observed in AD brains. Sucrose gradient fractionation showed that Aftin-4
      perturbs the subcellular localization of gamma-secretase components and could,
      therefore, modify gamma-secretase specificity by locally altering its membrane
      environment. Remarkably, Aftin-4 shares all these properties with two other "AD
      accelerator" compounds. In summary, treatment with three Abeta42 raising agents
      induced similar biochemical alterations that lead to comparable cellular
      phenotypes in vitro, suggesting a common mechanism of action involving three
      structural cellular targets.

PMID- 22972919
TI  - A natural point mutation changes both target selectivity and mechanism of action
      of sea anemone toxins.
AB  - APETx3, a novel peptide isolated from the sea anemone Anthopleura elegantissima,
      is a naturally occurring mutant from APETx1, only differing by a Thr to Pro
      substitution at position 3. APETx1 is believed to be a selective modulator of
      human ether-a-go-go related gene (hERG) potassium channels with a K(d) of 34 nM.
      In this study, APETx1, 2, and 3 have been subjected to an electrophysiological
      screening on a wide range of 24 ion channels expressed in Xenopus laevis oocytes:
      10 cloned voltage-gated sodium channels (Na(V) 1.2-Na(V)1.8, the insect channels
      DmNa(V)1, BgNa(V)1-1a, and the arachnid channel VdNa(V)1) and 14 cloned voltage
      gated potassium channels (K(V)1.1-K(V)1.6, K(V)2.1, K(V)3.1, K(V)4.2, K(V)4.3,
      K(V)7.2, K(V)7.4, hERG, and the insect channel Shaker IR). Surprisingly, the
      Thr3Pro substitution results in a complete abolishment of APETx3 modulation on
      hERG channels and provides this toxin the ability to become a potent (EC(50) 276
      nM) modulator of voltage-gated sodium channels (Na(V)s) because it slows down the
      inactivation of mammalian and insect Na(V) channels. Our study also shows that
      the homologous toxins APETx1 and APETx2 display promiscuous properties since they
      are also capable of recognizing Na(V) channels with IC(50) values of 31 nM and
      114 nM, respectively, causing an inhibition of the sodium conductance without
      affecting the inactivation. Our results provide new insights in key residues that
      allow these sea anemone toxins to recognize distinct ion channels with similar
      potency but with different modulatory effects. Furthermore, we describe for the
      first time the target promiscuity of a family of sea anemone toxins thus far
      believed to be highly selective.

PMID- 22972920
TI  - B7x in the periphery abrogates pancreas-specific damage mediated by self-reactive
      CD8 T cells.
AB  - B7x (B7-H4 or B7S1) is the seventh member of the B7 family, and its in vivo
      function remains largely unknown. Despite new genetic data linking the B7x gene
      with autoimmune diseases, how exactly it contributes to peripheral tolerance and
      autoimmunity is unclear. In this study, we showed that B7x protein was not
      detected on APCs or T cells in both human and mice, which is unique in the B7
      family. Because B7x protein is expressed in some peripheral cells such as
      pancreatic beta cells, we used a CD8 T cell-mediated diabetes model
      (AI4alphabeta) in which CD8 T cells recognize an endogenous self-Ag, and found
      that mice lacking B7x developed more severe diabetes than control AI4alphabeta
      mice. Conversely, mice overexpressing B7x in the beta cells (Rip-B7xAI4alphabeta)
      were diabetes free. Furthermore, adoptive transfer of effector AI4alphabeta CD8 T
      cells induced diabetes in control mice, but not in Rip-B7xAI4alphabeta mice.
      Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of
      migrating to the pancreas but failed to robustly destroy tissue when encountering
      local B7x in Rip-B7xAI4alphabeta mice. Although AI4alphabeta CD8 T cells in Rip
      B7xAI4alphabeta and AI4alphabeta mice showed similar cytotoxic function, cell
      death, and global gene expression profiles, these cells had greater proliferation
      in AI4alphabeta mice than in RIP-B7xAI4alphabeta mice. These results suggest that
      B7x in nonlymphoid organs prevents peripheral autoimmunity partially through
      inhibiting proliferation of tissue-specific CD8 T cells, and that local
      overexpression of B7x on pancreatic beta cells is sufficient to abolish CD8 T
      cell-induced diabetes.

PMID- 22972921
TI  - Inhibitors of DNA binding proteins restrict T cell potential by repressing Notch1
      expression in Flt3-negative common lymphoid progenitors.
AB  - Lineage commitment is regulated during hematopoiesis, with stepwise loss of
      differentiation potential ultimately resulting in lineage commitment. In this
      study we describe a novel population of B/NK bipotent precursors among common
      lymphoid progenitors in the fetal liver and the bone marrow. The absence of T
      cell precursor potential, both in vivo and in vitro, is due to low Notch1
      expression and secondary to inhibition of E2A activity by members of the
      inhibitor of DNA binding (Id) protein family. Our results demonstrate a new, Id
      protein-dependent, molecular mechanism of Notch1 repression, operative in both
      fetal and adult common lymphoid progenitors, where T cell potential is
      selectively inhibited without affecting either the B or NK programs. This study
      identifies Id proteins as negative regulators of T cell specification, before B
      and NK commitment, and provides important insights into the transcriptional
      networks orchestrating hematopoiesis.

PMID- 22972922
TI  - Role of macrophage migration inhibitory factor in the regulatory T cell response
      of tumor-bearing mice.
AB  - Macrophage migration inhibitory factor (MIF) is involved in tumorigenesis by
      facilitating tumor proliferation and evasion of apoptosis; however, its role in
      tumor immunity is unclear. In this study, we investigated the effect of MIF on
      the progression of the syngenic, CT26 colon carcinoma and the generation of tumor
      regulatory T cells (Tregs). The results showed that the tumor growth rate was
      significantly lower in MIF knockout (MIF(-/-)) mice than in wild-type (MIF(+/+))
      mice. Flow cytometric analysis of both spleen and tumor cells revealed that MIF(
      /-) mice had significantly lower levels of tumor-associated CD4(+)Tregs than
      MIF(+/+) mice. The splenic cells of MIF(-/-) mice also showed a decrease in
      CD8(+)Tregs, which was accompanied by an increase in CD8-induced tumor
      cytotoxicity. Interestingly, the inducible Treg response in spleen cells to anti
      CD3/CD28 plus IL-2 plus TGF-beta was greater in MIF(-/-) mice than in MIF(+/+)
      mice. Spleen cells of MIF(-/-) mice, stimulated with anti-CD3/CD28, produced
      lower levels of IL-2, but not TGF-beta, than those of MIF(+/+) mice, which was
      recovered by the addition of recombinant MIF. Conversely, a neutralizing anti-MIF
      Ab blocked anti-CD3-induced IL-2 production by splenocytes of MIF(+/+) mice and
      suppressed the inducible Treg generation. Moreover, the administration of IL-2
      into tumor-bearing MIF(-/-) mice restored the generation of Tregs and tumor
      growth. Taken together, our data suggest that MIF promotes tumor growth by
      increasing Treg generation through the modulation of IL-2 production. Thus, anti
      MIF treatment might be useful in enhancing the adaptive immune response to colon
      cancers.

PMID- 22972923
TI  - Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance
      of an arthritogenic alphavirus.
AB  - Chikungunya virus (CHIKV) and Ross River virus (RRV) cause a debilitating, and
      often chronic, musculoskeletal inflammatory disease in humans. Macrophages
      constitute the major inflammatory infiltrates in musculoskeletal tissues during
      these infections. However, the precise macrophage effector functions that affect
      the pathogenesis of arthritogenic alphaviruses have not been defined. We
      hypothesized that the severe damage to musculoskeletal tissues observed in RRV-
      or CHIKV-infected mice would promote a wound-healing response characterized by M2
      like macrophages. Indeed, we found that RRV- and CHIKV-induced musculoskeletal
      inflammatory lesions, and macrophages present in these lesions, have a unique
      gene-expression pattern characterized by high expression of arginase 1 and
      Ym1/Chi3l3 in the absence of FIZZ1/Relmalpha that is consistent with an M2-like
      activation phenotype. Strikingly, mice specifically deleted for arginase 1 in
      neutrophils and macrophages had dramatically reduced viral loads and improved
      pathology in musculoskeletal tissues at late times post-RRV infection. These
      findings indicate that arthritogenic alphavirus infection drives a unique myeloid
      cell activation program in inflamed musculoskeletal tissues that inhibits virus
      clearance and impedes disease resolution in an arginase 1-dependent manner.

PMID- 22972925
TI  - Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.
AB  - Multiple epidemiologic studies demonstrate associations between chronic beryllium
      disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a
      glutamic acid residue at position 69 (E69). Results suggest that the less
      frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater
      risk of CBD. In this study, we sought to define specific E69-carrying alleles and
      their amino acid sequences in the DP peptide binding groove, as well as their
      relationship to CBD and BeS risk, using the largest case control study to date.
      We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three
      beryllium industries who gave informed consent for participation. Non-Hispanic
      white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes
      were determined using sequence-specific primer PCR. The E69 alleles were tested
      for association with disease individually and grouped by amino acid structure
      using logistic regression. The results show that CBD cases were more likely than
      controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95%
      confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001).
      Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD
      versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL
      versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001.
      Similar results were found within the BeS group and CBD/BeS combined group. We
      conclude that the less frequent E69 alleles confer more risk for CBD than does
      *0201. Recent studies examining how the composition and structure of the binding
      pockets influence peptide binding in MHC genes, as well of studies showing the
      topology of the TCR to likely bind DPB1 preferentially, give plausible biological
      rationale for these findings.

PMID- 22972924
TI  - IFN-alpha and lipopolysaccharide upregulate APOBEC3 mRNA through different
      signaling pathways.
AB  - APOBEC3 (A3) proteins are virus-restriction factors that provide intrinsic
      immunity against infections by viruses like HIV-1 and mouse mammary tumor virus.
      A3 proteins are inducible by inflammatory stimuli, such as LPS and IFN-alpha, via
      mechanisms that are not fully defined. Using genetic and pharmacological studies
      on C57BL/6 mice and cells, we show that IFN-alpha and LPS induce A3 via different
      pathways, independently of each other. IFN-alpha positively regulates mouse
      APOBEC3 (mA3) mRNA expression through IFN-alphaR/PKC/STAT1 and negatively
      regulates mA3 mRNA expression via IFN-alphaR/MAPKs-signaling pathways.
      Interestingly, LPS shows some variation in its regulatory behavior. Although LPS
      mediated positive regulation of mA3 mRNA occurs through TLR4/TRIF/IRF3/PKC, it
      negatively modulates mA3 mRNA via TLR4/MyD88/MAPK-signaling pathways. Additional
      studies on human peripheral blood mononuclear cells reveal that PKC
      differentially regulates IFN-alpha and LPS induction of human A3A, A3F, and A3G
      mRNA expression. In summary, we identified important signaling targets downstream
      of IFN-alphaR and TLR4 that mediate A3 mRNA induction by both LPS and IFN-alpha.
      Our results provide new insights into the signaling targets that could be
      manipulated to enhance the intracellular store of A3 and potentially enhance A3
      antiviral function in the host.

PMID- 22972926
TI  - MicroRNAs control the maintenance of thymic epithelia and their competence for T
      lineage commitment and thymocyte selection.
AB  - Thymic epithelial cells provide unique cues for the lifelong selection and
      differentiation of a repertoire of functionally diverse T cells. Rendered
      microRNA (miRNA) deficient, these stromal cells in the mouse lose their capacity
      to instruct the commitment of hematopoietic precursors to a T cell fate, to
      effect thymocyte positive selection, and to achieve promiscuous gene expression
      required for central tolerance induction. Over time, the microenvironment created
      by miRNA-deficient thymic epithelia assumes the cellular composition and
      structure of peripheral lymphoid tissue, where thympoiesis fails to be supported.
      These findings emphasize a global role for miRNA in the maintenance and function
      of the thymic epithelial cell scaffold and establish a novel mechanism how these
      cells control peripheral tissue Ag expression to prompt central immunological
      tolerance.

PMID- 22972927
TI  - Blockade of IL-10 signaling during bacillus Calmette-Guerin vaccination enhances
      and sustains Th1, Th17, and innate lymphoid IFN-gamma and IL-17 responses and
      increases protection to Mycobacterium tuberculosis infection.
AB  - Vaccination with Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains the
      only prophylactic vaccine against tuberculosis, caused by Mycobacterium
      tuberculosis, but gives variable protection against pulmonary disease. The
      generation of host Th1 responses following BCG vaccination is accepted as the
      major mechanism of protection against M. tuberculosis infection. Early production
      of IL-17 in the lungs following M. tuberculosis challenge of mice previously
      vaccinated with M. tuberculosis peptides in adjuvant has been shown to be
      required for efficient Th1 cell recruitment. IL-10 regulates various processes
      involved in generation of Th1 and Th17 responses. Previous studies have shown IL
      10 as a negative regulator of the immune response to primary M. tuberculosis
      infection, with Il10(-/-) mice having reduced lung bacterial loads. In this study
      we show that inhibition of IL-10 signaling during BCG vaccination enhances host
      generated Ag-specific IFN-gamma and IL-17A responses, and that this regimen gives
      significantly greater protection against aerogenic M. tuberculosis challenge in
      both susceptible and relatively resistant strains of mice. In M. tuberculosis
      susceptible CBA/J mice, Ab blockade of IL-10R specifically during BCG vaccination
      resulted in additional protection against M. tuberculosis challenge of >1-log(10)
      compared with equivalent isotype-treated controls. The protection observed
      following BCG vaccination concurrent with anti-IL-10R mAb treatment was sustained
      through chronic M. tuberculosis infection and correlated with enhanced lung Th1
      and Th17 responses and increased IFN-gamma and IL-17A production by gammadelta T
      cells and an innate-like Thy1.2(+)CD3(-) lymphoid population. We show that IL-10
      inhibits optimal BCG-elicited protection, therefore suggesting that antagonists
      of IL-10 may be of great benefit as adjuvants in preventive vaccination against
      tuberculosis.

PMID- 22972928
TI  - Dendritic cell-specific disruption of TGF-beta receptor II leads to altered
      regulatory T cell phenotype and spontaneous multiorgan autoimmunity.
AB  - In vitro data and transgenic mouse models suggest a role for TGF-beta signaling
      in dendritic cells (DCs) to prevent autoimmunity primarily through maintenance of
      DCs in their immature and tolerogenic state characterized by low expression of
      MHC class II (MHCII) and costimulatory molecules and increased expression of IDO,
      among others. To test whether a complete lack of TGF-beta signaling in DCs
      predisposes mice to spontaneous autoimmunity and to verify the mechanisms
      implicated previously in vitro, we generated conditional knockout (KO) mice with
      Cre-mediated DC-specific deletion of Tgfbr2 (DC-Tgfbr2 KO). DC-Tgfbr2 KO mice die
      before 15 wk of age with multiorgan autoimmune inflammation and spontaneous
      activation of T and B cells. Interestingly, there were no significant differences
      in the expression of MHCII, costimulatory molecules, or IDO in secondary lymphoid
      organ DCs, although Tgfbr2-deficient DCs were more proinflammatory in vitro and
      in vivo. DC-Tgfbr2 KO showed attenuated Foxp3 expression in regulatory T cells
      (Tregs) and abnormal expansion of CD25(-)Foxp3(+) Tregs in vivo. Tgfbr2-deficient
      DCs secreted elevated levels of IFN-gamma and were not capable of directing Ag
      specific Treg conversion unless in the presence of anti-IFN-gamma blocking Ab.
      Adoptive transfer of induced Tregs into DC-Tgfbr2 KO mice partially rescued the
      phenotype. Therefore, in vivo, TGF-beta signaling in DCs is critical in the
      control of autoimmunity through both Treg-dependent and -independent mechanisms,
      but it does not affect MHCII and costimulatory molecule expression.

PMID- 22972929
TI  - CD11c+ cells are required for antigen-induced increase of mast cells in the lung.
AB  - Patients with allergic asthma have more lung mast cells, which likely worsens the
      symptoms. In experimental asthma, CD11c(+) cells have to be present during the
      challenge phase for several features of allergic inflammation to occur. Whether
      CD11c(+) cells play a role for Ag-induced increases of lung mast cells is
      unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c
      diphtheria toxin receptor transgenic mice to deplete CD11c(+) cells. We
      demonstrate that recruitment of mast cell progenitors to the lung is
      substantially reduced when CD11c(+) cells are depleted during the challenge
      phase. This correlated with an impaired induction of endothelial VCAM-1 and led
      to a significantly reduced number of mature mast cells 1 wk after challenge.
      Collectively, these data suggest that Ag challenge stimulates CD11c(+) cells to
      produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung
      endothelium, which in turn is crucial for the Ag-induced mast cell progenitor
      recruitment and the increase in mast cell numbers.

PMID- 22972931
TI  - Regulation of inflammatory response by 3-methyladenine involves the coordinative
      actions on Akt and glycogen synthase kinase 3beta rather than autophagy.
AB  - 3-Methyladenine (3-MA) is one of the most commonly used inhibitors in autophagy
      research today. However, rather than inhibiting class III PI3K that is involved
      in autophagy suppression, 3-MA might also interfere with class I PI3K and
      consequently augment autophagy flux. In this study, we aim to get a thorough
      understanding on the action mechanisms of 3-MA in TLR4-mediated inflammatory
      responses in RAW264.7 macrophages and, moreover, to decipher the action of 3-MA
      in modulation of autophagy. We found that 3-MA could enhance LPS-induced NF
      kappaB activation and production of TNF-alpha, inducible NO synthase (iNOS),
      cyclooxygenase-2, IL-1beta, and IL-12. In contrast, 3-MA suppressed LPS-induced
      IFN-beta production and STAT signaling. Studies revealed that 3-MA can, through
      inhibition of Akt as a result of class I PI3K interference, positively regulate
      p38, JNK, and p65, but negatively regulate TANK-binding kinase 1 and IFN
      regulatory factor 3 mediated by TLR4. As glycogen synthase kinase 3beta
      (GSK3beta) is an important Akt substrate, we further explored its involvement in
      the actions of 3-MA. 3-MA was found to enhance LPS-induced NF-kappaB activation,
      iNOS, and pro-IL-1beta expression, and these actions were reversed by either
      GSK3beta inhibitors or small interfering GSK3beta. Lastly, we demonstrated that 3
      MA acts as an autophagy inducer in RAW264.7 macrophages, but the stimulating
      effects on NF-kappaB activation and iNOS and cyclooxygenase-2 expression were not
      affected in LPS-stimulated macrophages with small interfering autophagy protein-5
      treatment. These results not only shed new light on the action mechanisms of 3-MA
      to differentially regulate inflammatory outcomes derived from TLR4-mediated MyD88
      and Toll/IL-1R domain-containing adapter inducing IFN-beta pathways, but also
      highlight the necessity to check autophagy status upon taking 3-MA as a general
      autophagy inhibitor.

PMID- 22972930
TI  - IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B
      virus infection.
AB  - A regulatory subset of B cells has been found to modulate immune responses in
      autoimmunity, infection, and cancer, but it has not been investigated in the
      setting of human persistent viral infection. IL-10 is elevated in patients with
      chronic hepatitis B virus infection (CHB), but its cellular sources and impact on
      antiviral T cells have not been addressed. We investigated the role of IL-10 and
      regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied
      longitudinally in patients with CHB undergoing spontaneous disease flares. There
      was a close temporal correlation between IL-10 levels and fluctuations in viral
      load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional
      virus-specific CD8 T cell responses. To investigate the potential contribution of
      regulatory B cells, their frequency was measured directly ex vivo and after
      exposure to stimuli relevant to hepatitis B virus (HBV) (CpG or HBV Ags). IL-10
      producing B cells were enriched in patients, and their frequency correlated
      temporally with hepatic flares, both after stimulation and directly ex vivo.
      Phenotypically, these cells were predominantly immature (CD19(+)CD24(hi)CD38(hi))
      ex vivo; sorted CD19(+)CD24(hi)CD38(hi) cells suppressed HBV-specific CD8 T cell
      responses in an IL-10-dependent manner. In summary, these data reveal a novel IL
      10-producing subset of B cells able to regulate T cell immunity in CHB.

PMID- 22972932
TI  - Extensive diversification of IgD-, IgY-, and truncated IgY(deltaFc)-encoding
      genes in the red-eared turtle (Trachemys scripta elegans).
AB  - IgY(DeltaFc), containing only CH1 and CH2 domains, is expressed in the serum of
      some birds and reptiles, such as ducks and turtles. The duck IgY(DeltaFc) is
      produced by the same upsilon gene that expresses the intact IgY form (CH1-4)
      using different transcriptional termination sites. In this study, we show that
      intact IgY and IgY(DeltaFc) are encoded by distinct genes in the red-eared turtle
      (Trachemys scripta elegans). At least eight IgY and five IgY(DeltaFc) transcripts
      were found in a single turtle. Together with Southern blotting, our data suggest
      that multiple genes encoding both IgY forms are present in the turtle genome.
      Both of the IgY forms were detected in the serum using rabbit polyclonal Abs. In
      addition, we show that multiple copies of the turtle delta gene are present in
      the genome and that alternative splicing is extensively involved in the
      generation of both the secretory and membrane-bound forms of the IgD H chain
      transcripts. Although a single MU gene was identified, the alpha gene was not
      identified in this species.

PMID- 22972933
TI  - Autophagy regulates IL-23 secretion and innate T cell responses through effects
      on IL-1 secretion.
AB  - Autophagy controls IL-1beta secretion by regulating inflammasome activation and
      by targeting pro-IL-1beta for degradation. In this article, we show that
      inhibition of autophagy, either with the PI3K inhibitors 3-methyladenine,
      wortmannin, and LY294002 or with small interfering RNA against autophagy proteins
      augmented the secretion of IL-23 by human and mouse macrophages and dendritic
      cells in response to specific TLR agonists. This process occurred at the
      transcriptional level and was dependent on reactive oxygen species and IL-1R
      signaling; it was abrogated with an IL-1R antagonist or with IL-1-neutralizing
      Abs, whereas treatment with either rIL-1alpha or IL-1beta induced IL-23
      secretion. Dendritic cells treated with LPS and 3-methyladenine secreted enhanced
      levels of both IL-1beta and IL-23, and supernatants from these cells stimulated
      the innate secretion of IL-17, IFN-gamma, and IL-22 by gammadelta T cells. These
      data demonstrate that autophagy has a potentially pivotal role to play in the
      induction and regulation of inflammatory responses by innate immune cells,
      largely driven by IL-1 and its consequential effects on IL-23 secretion.

PMID- 22972934
TI  - Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte
      differentiation.
AB  - The Mediator complex functions as a control center, orchestrating diverse
      signaling, gene activities, and biological processes. However, how Mediator
      subunits determine distinct cell fates remains to be fully elucidated. Here, we
      show that Mediator MED23 controls the cell fate preference that directs
      differentiation into smooth muscle cells (SMCs) or adipocytes. Med23 deficiency
      facilitates SMC differentiation but represses adipocyte differentiation from the
      multipotent mesenchymal stem cells. Gene profiling revealed that the presence or
      absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL targeted
      cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipogenic genes.
      Mechanistically, MED23 favors ELK1-SRF binding to SMC gene promoters for
      repression, whereas the lack of MED23 favors MAL-SRF binding to SMC gene
      promoters for activation. Remarkably, the effect of MED23 on SMC differentiation
      can be recapitulated in zebrafish embryogenesis. Collectively, our data
      demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC
      and growth/adipogenic gene programs, suggesting its "Ying-Yang" function in
      directing adipogenesis versus SMC differentiation.

PMID- 22972935
TI  - Age-associated inflammation inhibits epidermal stem cell function.
AB  - Altered stem cell homeostasis is linked to organismal aging. However, the
      mechanisms involved remain poorly understood. Here we report novel alterations in
      hair follicle stem cells during skin aging, including increased numbers,
      decreased function, and an inability to tolerate stress. Performing high
      throughput RNA sequencing on aging stem cells, cytokine arrays, and functional
      assays, we identify an age-associated imbalance in epidermal Jak-Stat signaling
      that inhibits stem cell function. Collectively, this study reveals a role for the
      aging epidermis in the disruption of cytokine and stem cell homeostasis,
      suggesting that stem cell decline during aging may be part of broader tumor
      suppressive mechanisms.

PMID- 22972936
TI  - Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs).
AB  - The Hippo signaling pathway plays a crucial role in tissue growth and
      tumorigenesis. Core components of the Hippo pathway include the MST1/2 and
      Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ
      transcription coactivators, which are inhibited through phosphorylation by Lats.
      However, upstream signals that regulate the Hippo pathway have not been well
      delineated. Here we report that stimulation of protease-activated receptors
      (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear
      localization. PAR1 acts through G(12/13) and Rho GTPase to inhibit the Lats1/2
      kinase. Our observations establish thrombin as a physiological signal for the
      Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR
      activation.

PMID- 22972937
TI  - Mixing of the old with the new: nanoparticle-mediated pioglitazone delivery to
      enhance therapeutic neovascularization.

PMID- 22972938
TI  - Do vivarium conditions influence atherosclerotic lesion size?

PMID- 22972939
TI  - SOAPindel: efficient identification of indels from short paired reads.
AB  - We present a new approach to indel calling that explicitly exploits that indel
      differences between a reference and a sequenced sample make the mapping of reads
      less efficient. We assign all unmapped reads with a mapped partner to their
      expected genomic positions and then perform extensive de novo assembly on the
      regions with many unmapped reads to resolve homozygous, heterozygous, and complex
      indels by exhaustive traversal of the de Bruijn graph. The method is implemented
      in the software SOAPindel and provides a list of candidate indels with quality
      scores. We compare SOAPindel to Dindel, Pindel, and GATK on simulated data and
      find similar or better performance for short indels (<10 bp) and higher
      sensitivity and specificity for long indels. A validation experiment suggests
      that SOAPindel has a false-positive rate of ~10% for long indels (>5 bp), while
      still providing many more candidate indels than other approaches.

PMID- 22972940
TI  - Twenty-four-hour mobility during acute hospitalization in older medical patients.
AB  - BACKGROUND: Inactivity during hospitalization in older medical patients may lead
      to functional decline. This study quantified 24-hour mobility, validated the
      accelerometers used, and assessed the daily level of basic mobility in acutely
      admitted older medical patients during their hospitalization. METHODS: This is a
      prospective cohort study in older medical patients able to walk independently
      (ambulatory patients) and those not able to walk independently (nonambulatory
      patients) on admission. The 24-hour mobility level during hospitalization was
      assessed by measuring the time in lying, sitting, and standing and/or walking, by
      two accelerometers. Basic mobility was quantified within 48 hours of admission
      and repeated daily throughout hospitalization. RESULTS: Forty-three ambulatory
      patients and six nonambulatory patients were included. The ambulatory patients
      tended to be hospitalized for fewer days than the nonambulatory patients (7 vs
      16, p = .13). The ambulatory patients were lying median 17 hours, (interquartile
      range [IQR]: 14.4-19.1), sitting 5.1 hours (IQR: 2.9-7.1), and standing and/or
      walking 1.1 hours (IQR: 0.6-1.7) per day. On days with independency in basic
      mobility, the ambulatory patients were lying 4.1 hours less compared with days
      with dependency in basic mobility (p < .0001), sitting 2.4 hours more (p =
      .0004), and standing 0.9 hours more (p < .0001). The algorithm identification for
      lying, sitting, and standing and/or walking of the accelerometers, corresponded
      by 89%-100% with positions performed by older medical patients. CONCLUSIONS:
      Older acutely hospitalized medical patients with walking ability spent 17h/d of
      their in-hospital time in bed, and the level of in-hospital mobility seemed to
      depend on the patients' level of basic mobility. The accelerometers were valid in
      assessing mobility in older medical patients.

PMID- 22972941
TI  - Adverse clinical events and mortality during hospitalization and 3 months after
      discharge in cognitively impaired elderly patients.
AB  - BACKGROUND: Controversial findings are reported on hospital outcome in
      cognitively impaired patients. The aim of this study was to explore mortality
      risk according to cognitive status during hospitalization and after 3 months in
      elderly patients. METHODS: Sixty-six internal medicine and geriatric wards in
      Italy participated in the "Registry Politerapie SIMI (REPOSI)" during 2010. Of
      the 1,380 in-patients, aged 65 and older enrolled, 1,201 were included. Cognition
      was evaluated with the Short Blessed Test (SBT). Logistic regression was used to
      evaluate the association of questionable and impaired cognition (according to SBT
      cutoff points) with mortality during hospitalization and at follow-up. Morbidity,
      function, and adverse events during hospitalization were covariates. RESULTS:
      Four hundred and twenty-one participants were classified as normal, 219
      questionable, and 561 cognitively impaired. Forty-nine patients died during
      hospitalization and 70 during follow-up. Sixty-seven point three percent versus
      32.7% (p < .001) of patients who died during hospitalization and 54.3% versus
      45.7% (p < .001) during follow-up had at least one adverse event. After
      multiadjustment, impaired cognition was associated with in-hospital mortality
      (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.1-8.6) but not with
      mortality at follow-up. Increase severity of cognitive impairment was associated
      with higher odds of mortality (from 2.7 in those with moderate impairment to 4.2
      in those with severe impairment). After stratification for adverse clinical
      events, impaired cognition resulted associated with mortality only in patients
      having at least one event. CONCLUSION: Elderly patients with cognitive impairment
      are more likely to die during hospitalization with a severity-dependent
      association. Adverse events may represent an important target of prevention due
      to their high association with mortality and cognitive impairment.

PMID- 22972945
TI  - Gene expression as a quantitative trait: what about translation?
AB  - BACKGROUND AND OBJECTIVE: Much progress has been made in determining loci where
      gene expression at the steady-state mRNA level is controlled by genetic variants
      in cis. However, mRNA is only a proxy for what matters in phenotypic variation,
      which is protein level. We set out to review the evidence for exonic
      polymorphisms that affect translation of mRNA. METHODS: Informal literature
      review. RESULTS: There is ample literature on monogenic diseases caused by rare
      mutations in translationally active mRNA elements. Such mutations may eliminate
      or create AUG initiation codons or alter the Kozak sequences surrounding them,
      alter RNA secondary structure, destroy or enhance internal ribosomal entry
      sequences or Fe-response elements. By contrast, examples of complex phenotypes
      determined by common polymorphisms in these elements are scarce, although reports
      (to be confirmed) of functionally polymorphic miRNA binding sites are beginning
      to appear. CONCLUSIONS: Given the methodological limitations of detecting these
      translational effects, we posit that existing knowledge of such effects in common
      complex phenotypes represent the 'tip of the iceberg'. High-throughput
      quantitative proteomics is beginning to offer a promise to explore this
      possibility.

PMID- 22972942
TI  - Antihypertensive drug class use and differential risk of urinary incontinence in
      community-dwelling older women.
AB  - BACKGROUND: Medication use is a potentially reversible cause of urinary
      incontinence (UI). The objective of this longitudinal cohort study was to
      evaluate whether self-reported UI in community-dwelling older women is associated
      with the use of different classes of antihypertensive agents. METHODS: The sample
      consisted of 959 black and white women aged 72-81 years without baseline (Year 1)
      UI from the Health, Aging, and Body Composition Study. Use of any
      antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha
      blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II
      receptor blockers, beta blockers, calcium channel blockers, diuretics [loop],
      diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was
      determined during Year 3 in-person interviews. The number of unique
      antihypertensive agents used and the standardized daily dosage were also
      examined. Self-reported UI, operationally defined as leaking urine at least
      weekly during the previous 12 months, was assessed at Year 4 visits. RESULTS: A
      total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive
      use, number of agents used, and standardized daily dosage at Year 3 were not
      associated with UI at Year 4, use of one particular drug class-peripheral alpha
      blockers (ie, doxazosin, prazosin, and terazosin)-was associated with fourfold
      greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79
      11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in
      those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence
      interval = 1.78-43.53; p = .0076). CONCLUSION: In community-dwelling older women,
      peripheral alpha blocker use was associated with UI, and the odds nearly doubled
      when used with loop diuretics.

PMID- 22972946
TI  - Closing the case of APOE in multiple sclerosis: no association with disease risk
      in over 29 000 subjects.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (epsilon4) and rs7412
      (epsilon2), both invoking changes in the amino-acid sequence of the
      apolipoprotein E (APOE) gene, have previously been tested for association with
      multiple sclerosis (MS) risk. However, none of these studies was sufficiently
      powered to detect modest effect sizes at acceptable type-I error rates. As both
      SNPs are only imperfectly captured on commonly used microarray genotyping
      platforms, their evaluation in the context of genome-wide association studies has
      been hindered until recently. METHODS: We genotyped 12 740 subjects hitherto not
      studied for their APOE status, imputed raw genotype data from 8739 subjects from
      five independent genome-wide association studies datasets using the most recent
      high-resolution reference panels, and extracted genotype data for 8265 subjects
      from previous candidate gene assessments. RESULTS: Despite sufficient power to
      detect associations at genome-wide significance thresholds across a range of ORs,
      our analyses did not support a role of rs429358 or rs7412 on MS susceptibility.
      This included meta-analyses of the combined data across 13 913 MS cases and 15
      831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412,
      respectively). CONCLUSION: Given the large sample size of our analyses, it is
      unlikely that the two APOE missense SNPs studied here exert any relevant effects
      on MS susceptibility.

PMID- 22972947
TI  - Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with
      punctate palmoplantar keratoderma.
AB  - BACKGROUND: Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant
      skin disorder characterised by numerous hyperkeratotic papules irregularly
      distributed on the palms and soles. To date, no causal gene for this disease has
      been identified. METHODS: We performed exome sequencing analysis of four affected
      individuals and two unaffected controls from one Chinese PPPK family where
      disease locus was mapped at 8q24.13-8q24.21 by our previous linkage analysis.
      RESULTS: We identified a novel heterozygous mutation in COL14A1 gene (c.4505C->T
      (p.Pro1502Leu)), which located within the linkage region that we previously
      identified for PPPK. The mutation was shared by the four affected individuals,
      but not for the two controls of the family. Sanger sequencing confirmed this
      mutation in another four cases from this family. This mutation was invisible in
      the normal controls of this family as well as the additional 676 unrelated normal
      controls and 781 patients with other disease. The shared COL14A1 mutation,
      p.Pro1502Leu, is a missense substitution at a highly conserved amino acid residue
      across multiple species. CONCLUSIONS: The power of combining exome sequencing and
      linkage information in the study of genetics of autosomal dominant disorders,
      even in simplex cases, has been demonstrated. Our results suggested that COL14A1
      would be a casual gene for PPPK, which was helpful for advancing us on
      understanding of the pathogenesis of PPPK.

PMID- 22972949
TI  - Complex I deficiency: clinical features, biochemistry and molecular genetics.
AB  - Complex I deficiency is the most frequent mitochondrial disorder presenting in
      childhood, accounting for up to 30% of cases. As with many mitochondrial
      disorders, complex I deficiency is characterised by marked clinical and genetic
      heterogeneity, leading to considerable diagnostic challenges for the clinician,
      not least because of the involvement of two genomes. The most prevalent clinical
      presentations include Leigh syndrome, leukoencephalopathy and other early-onset
      neurodegenerative disorders; fatal infantile lactic acidosis; hypertrophic
      cardiomyopathy; and exercise intolerance. Causative genetic defects may involve
      the seven mitochondrial-encoded or 38 nuclear-encoded subunits of the enzyme, or
      any of an increasing number of assembly factors implicated in the correct
      biosynthesis of complex I within the inner mitochondrial membrane. In this
      review, we discuss recent advances in knowledge of the structure, function and
      assembly of complex I and how these advances, together with new high-throughput
      genetic screening techniques, have translated into improved genetic diagnosis for
      affected patients and their families. Approximately 25% of cases have
      mitochondrial DNA mutations, while a further ~25% have mutations in a nuclear
      subunit or in one of nine known assembly factors. We also present a systematic
      review of all published cases of nuclear-encoded complex I deficiency, including
      117 cases with nuclear subunit mutations and 55 with assembly factor mutations,
      and highlight clinical, radiological and biochemical clues that may expedite
      genetic diagnosis.

PMID- 22972948
TI  - Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated
      mitochondrial complex II deficiency.
AB  - BACKGROUND: Isolated complex II deficiency is a rare form of mitochondrial
      disease, accounting for approximately 2% of all respiratory chain deficiency
      diagnoses. The succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC and SDHD)
      are autosomally-encoded and transcribe the conjugated heterotetramers of complex
      II via the action of two known assembly factors (SDHAF1 and SDHAF2). Only a
      handful of reports describe inherited SDH gene defects as a cause of paediatric
      mitochondrial disease, involving either SDHA (Leigh syndrome, cardiomyopathy) or
      SDHAF1 (infantile leukoencephalopathy). However, all four SDH genes, together
      with SDHAF2, have known tumour suppressor functions, with numerous germline and
      somatic mutations reported in association with hereditary cancer syndromes,
      including paraganglioma and pheochromocytoma. METHODS AND RESULTS: Here, we
      report the clinical and molecular investigations of two patients with
      histochemical and biochemical evidence of a severe, isolated complex II
      deficiency due to novel SDH gene mutations; the first patient presented with
      cardiomyopathy and leukodystrophy due to compound heterozygous p.Thr508Ile and
      p.Ser509Leu SDHA mutations, while the second patient presented with hypotonia and
      leukodystrophy with elevated brain succinate demonstrated by MR spectroscopy due
      to a novel, homozygous p.Asp48Val SDHB mutation. Western blotting and BN-PAGE
      studies confirmed decreased steady-state levels of the relevant SDH subunits and
      impairment of complex II assembly. Evidence from yeast complementation studies
      provided additional support for pathogenicity of the SDHB mutation. CONCLUSIONS:
      Our report represents the first example of SDHB mutation as a cause of inherited
      mitochondrial respiratory chain disease and extends the SDHA mutation spectrum in
      patients with isolated complex II deficiency.

PMID- 22972950
TI  - Deletion of the 3q26 region including the EVI1 and MDS1 genes in a neonate with
      congenital thrombocytopenia and subsequent aplastic anaemia.
AB  - BACKGROUND: Gene-targeting studies in mice have revealed a key role for EVI1
      protein in the maintenance of haematopoiesis, and argue in favour of a gene
      dosage requirement for EVI1 in the regulation of haematopoietic stem cells.
      Furthermore, a fusion transcript of MDS1 and EVI1 has been shown to play a
      critical role in maintaining long-term haematopoietic stem cell function.
      Inappropriate activation of EVI1, usually due to a translocation, is a well known
      and unfavourable change in several myeloid malignancies. It is not known whether
      haploinsufficiency of any of these genes leads to disease in humans. METHODS: SNP
      array analysis in a patient with in a neonate with congenital thrombocytopenia
      and subsequent aplastic anaemia RESULTS AND CONCLUSIONS: We report for the first
      time a constitutional deletion encompassing the EVI1 and MDS1 genes in a human,
      and argue that the deletion causes congenital bone marrow failure in this
      patient.

PMID- 22972951
TI  - Prediction of breast cancer risk by genetic risk factors, overall and by hormone
      receptor status.
AB  - OBJECTIVE: There is increasing interest in adding common genetic variants
      identified through genome wide association studies (GWAS) to breast cancer risk
      prediction models. First results from such models showed modest benefits in terms
      of risk discrimination. Heterogeneity of breast cancer as defined by hormone
      receptor status has not been considered in this context. In this study we
      investigated the predictive capacity of 32 GWAS-detected common variants for
      breast cancer risk, alone and in combination with classical risk factors, and for
      tumours with different hormone receptor status. MATERIAL AND METHODS: Within the
      Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast
      cancer cases and 7827 matched controls of European ancestry, with data on
      classical breast cancer risk factors and 32 common gene variants identified
      through GWAS. Discriminatory ability with respect to breast cancer of specific
      hormone receptor-status was assessed with the age adjusted and cohort-adjusted
      concordance statistic (AUROC(a)). Absolute risk scores were calculated with
      external reference data. Integrated discrimination improvement was used to
      measure improvements in risk prediction. RESULTS: We found a small but steady
      increase in discriminatory ability with increasing numbers of genetic variants
      included in the model (difference in AUROC(a) going from 2.7% to 4%).
      Discriminatory ability for all models varied strongly by hormone receptor status.
      DISCUSSION AND CONCLUSIONS: Adding information on common polymorphisms provides
      small but statistically significant improvements in the quality of breast cancer
      risk prediction models. We consistently observed better performance for receptor
      positive cases, but the gain in discriminatory quality is not sufficient for
      clinical application.

PMID- 22972952
TI  - Intra- and interhemispheric connectivity between face-selective regions in the
      human brain.
AB  - Neuroimaging studies have revealed a number of regions in the human brain that
      respond to faces. However, the way these regions interact is a matter of current
      debate. The aim of this study was to use functional MRI to define face-selective
      regions in the human brain and then determine how these regions interact in a
      large population of subjects (n = 72). We found consistent face selectivity in
      the core face regions of the occipital and temporal lobes: the fusiform face area
      (FFA), occipital face area (OFA), and superior temporal sulcus (STS). Face
      selectivity extended into the intraparietal sulcus (IPS), precuneus (PCu),
      superior colliculus (SC), amygdala (AMG), and inferior frontal gyrus (IFG). We
      found evidence for significant functional connectivity between the core face
      selective regions, particularly between the OFA and FFA. However, we found that
      the covariation in activity between corresponding face regions in different
      hemispheres (e.g., right and left FFA) was higher than between different face
      regions in the same hemisphere (e.g., right OFA and right FFA). Although
      functional connectivity was evident between regions in the core and extended
      network, there were significant differences in the magnitude of the connectivity
      between regions. Activity in the OFA and FFA were most correlated with the IPS,
      PCu, and SC. In contrast, activity in the STS was most correlated with the AMG
      and IFG. Correlations between the extended regions suggest strong functional
      connectivity between the IPS, PCu, and SC. In contrast, the IFG was only
      correlated with the AMG. This study reveals that interhemispheric as well as
      intrahemispheric connections play an important role in face perception.

PMID- 22972954
TI  - Learning selective top-down control enhances performance in a visual
      categorization task.
AB  - We model the putative neuronal and synaptic mechanisms involved in learning a
      visual categorization task, taking inspiration from single-cell recordings in
      inferior temporal cortex (ITC). Our working hypothesis is that learning the
      categorization task involves both bottom-up, ITC to prefrontal cortex (PFC), and
      top-down (PFC to ITC) synaptic plasticity and that the latter enhances the
      selectivity of the ITC neurons encoding the task-relevant features of the
      stimuli, thereby improving the signal-to-noise ratio. We test this hypothesis by
      modeling both areas and their connections with spiking neurons and plastic
      synapses, ITC acting as a feature-selective layer and PFC as a category coding
      layer. This minimal model gives interesting clues as to properties and function
      of the selective feedback signal from PFC to ITC that help solving a
      categorization task. In particular, we show that, when the stimuli are very noisy
      because of a large number of nonrelevant features, the feedback structure helps
      getting better categorization performance and decreasing the reaction time. It
      also affects the speed and stability of the learning process and sharpens tuning
      curves of ITC neurons. Furthermore, the model predicts a modulation of neural
      activities during error trials, by which the differential selectivity of ITC
      neurons to task-relevant and task-irrelevant features diminishes or is even
      reversed, and modulations in the time course of neural activities that appear
      when, after learning, corrupted versions of the stimuli are input to the network.

PMID- 22972953
TI  - Brain surface temperature under a craniotomy.
AB  - Many neuroscientists access surface brain structures via a small cranial window,
      opened in the bone above the brain region of interest. Unfortunately this
      methodology has the potential to perturb the structure and function of the
      underlying brain tissue. One potential perturbation is heat loss from the brain
      surface, which may result in local dysregulation of brain temperature. Here, we
      demonstrate that heat loss is a significant problem in a cranial window
      preparation in common use for electrical recording and imaging studies in mice.
      In the absence of corrective measures, the exposed surface of the neocortex was
      at ~28 degrees C, ~10 degrees C below core body temperature, and a standing
      temperature gradient existed, with tissue below the core temperature even several
      millimeters into the brain. Cooling affected cellular and network function in
      neocortex and resulted principally from increased heat loss due to convection and
      radiation through the skull and cranial window. We demonstrate that constant
      perfusion of solution, warmed to 37 degrees C, over the brain surface readily
      corrects the brain temperature, resulting in a stable temperature of 36-38
      degrees C at all depths. Our results indicate that temperature dysregulation may
      be common in cranial window preparations that are in widespread use in
      neuroscience, underlining the need to take measures to maintain the brain
      temperature in many physiology experiments.

PMID- 22972955
TI  - Optical illusion alters M1 excitability after mirror therapy: a TMS study.
AB  - The contralesional primary motor cortex (M1) has been suggested to be involved in
      the motor recovery after mirror therapy, but whether the ipsilesional M1 is
      influenced by the contralesional M1 via transcallosal interhemispheric inhibition
      (IHI) is still unclear. The present study investigated the change of IHI as well
      as the intracortical inhibition and intracortical facilitation of both M1 induced
      by training in a mirror with the use of transcranial magnetic stimulation (TMS).
      In this 2 * 2 factorial design (time * group), healthy subjects exercised
      standardized motor skills with their right hand on four consecutive days. Either
      a mirror (mirror group) or a board (control group) was positioned between their
      hands. Before and after training TMS was applied along with training tests of
      both hands. Tests were the same motor skills exercised daily by both groups.
      Tests of the untrained left hand improved significantly more in the mirror group
      than in the control group after training (P = 0.02) and showed a close
      correlation with an increase of intracortical inhibition of M1(left). IHI did not
      show any difference between investigation time points and groups. The present
      study confirms the previous suggestion of the involvement of the "contralesional"
      left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy,
      which is not mediated by IHI. Even with the same motor skill training (both
      groups performed same motor skills) but with different visual information,
      different networks are involved in training-induced plasticity.

PMID- 22972958
TI  - An evaluation of in vivo voltage-sensitive dyes: pharmacological side effects and
      signal-to-noise ratios after effective removal of brain-pulsation artifacts.
AB  - In the current study, we investigated pharmacological side effects and signal-to
      noise ratios (SNRs) of two commonly used voltage-sensitive dyes (VSDs): the blue
      dye RH-1691 (1 mg/ml) and the red dye di-4-ANEPPS (0.1 mg/ml), applied in vivo to
      the rat barrel cortex. Blue dyes are often favored over red dyes in in vivo
      studies due to their apparent superior SNR, partly because their fluorescence
      spectrum is farther away from the hemoglobin absorption spectrum, making them
      less prone to heartbeat-associated brain-pulsation artifacts (BPA). We
      implemented a previously reported template-based BPA removal algorithm and
      evaluated its applicability to di-4-ANEPPS before comparing characteristics of
      the two dyes. Somatosensory-evoked potentials (SEPs) were also recorded. Whereas
      SEPs recorded before and after application of di-4-ANEPPS failed to exhibit
      demonstrable differences, RH-1691 caused a significant and prolonged increase in
      SEP amplitude for several hours. In contrast, neither dye influenced the
      spontaneous cortical activity as assessed by the spectral content of the EEG.
      Both dyes turned out to be strikingly similar with respect to changes in
      fractional fluorescence as a function of SEP response amplitude, as well as
      regarding shot noise characteristics after removal of the BPA. Thus there is
      strong evidence that the increased SNR for RH-1691 is a consequence of an
      artificially increased signal. When applying an appropriate BPA removal
      algorithm, di-4-ANEPPS has proven to be suitable for single-trial in vivo VSD
      imaging (VSDI) and produces no detectable neurophysiological changes in the
      system under investigation. Taken together, our data argue for a careful re
      evaluation of pharmacological side effects of RH-1691 and support the
      applicability of di-4-ANEPPS for stable single-trial in vivo VSDI recordings.

PMID- 22972956
TI  - Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory
      nerve activity.
AB  - The spatio-temporal pattern of auditory nerve (AN) activity, representing the
      relative timing of spikes across the tonotopic axis, contains cues to perceptual
      features of sounds such as pitch, loudness, timbre, and spatial location. These
      spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN)
      that are sensitive to relative timing of inputs from AN fibers innervating
      different cochlear regions. One possible mechanism for this extraction is "cross
      frequency" coincidence detection (CD), in which a central neuron converts the
      degree of coincidence across the tonotopic axis into a rate code by
      preferentially firing when its AN inputs discharge in synchrony. We used Huffman
      stimuli (Carney LH. J Neurophysiol 64: 437-456, 1990), which have a flat power
      spectrum but differ in their phase spectra, to systematically manipulate relative
      timing of spikes across tonotopically neighboring AN fibers without changing
      overall firing rates. We compared responses of CN units to Huffman stimuli with
      responses of model CD cells operating on spatio-temporal patterns of AN activity
      derived from measured responses of AN fibers with the principle of cochlear
      scaling invariance. We used the maximum likelihood method to determine the CD
      model cell parameters most likely to produce the measured CN unit responses, and
      thereby could distinguish units behaving like cross-frequency CD cells from those
      consistent with same-frequency CD (in which all inputs would originate from the
      same tonotopic location). We find that certain CN unit types, especially those
      associated with globular bushy cells, have responses consistent with cross
      frequency CD cells. A possible functional role of a cross-frequency CD mechanism
      in these CN units is to increase the dynamic range of binaural neurons that
      process cues for sound localization.

PMID- 22972957
TI  - Morphology, PKCdelta expression, and synaptic responsiveness of different types
      of rat central lateral amygdala neurons.
AB  - Recent findings implicate the central lateral amygdala (CeL) in conditioned fear.
      Indeed, CeL contains neurons exhibiting positive (CeL-On) or negative (CeL-Off)
      responses to fear-inducing conditioned stimuli (CSs). In mice, these cells differ
      in their expression of protein kinase Cdelta (PKCdelta) and physiological
      properties. CeL-Off cells are PKCdelta(+) and late firing (LF), whereas CeL-On
      cells are PKCdelta(-) and express a regular-spiking (RS) or low-threshold
      bursting (LTB) phenotype. However, the scarcity of LF cells in rats raises
      questions about the correspondence between the organization of CeL in mice and
      rats. Therefore, we studied the PKCdelta expression, morphological properties,
      synaptic responsiveness, and fear conditioning-induced plasticity of rat CeL
      neurons. No PKCdelta(+) LF cells were encountered, but ~20-25% of RS and LTB
      neurons were PKCdelta(+). Compared with RS neurons, a higher proportion of LTB
      cells projected to central medial amygdala (CeM) and they had fewer primary
      dendritic branches, yet the amplitude of excitatory postsynaptic potentials
      (EPSPs) evoked by lateral amygdala (LA) stimulation was similar in RS and LTB
      cells. In contrast, LA-evoked inhibitory postsynaptic potentials (IPSPs) had a
      higher amplitude in LTB than RS neurons. Finally, fear conditioning did not
      induce plasticity at LA inputs to RS or LTB neurons. These findings point to
      major species differences in the organization of CeL. Since rat LTB cells are
      subjected to stronger feedforward inhibition, they are more likely to exhibit
      inhibitory CS responses than RS cells. This is expected to cause a disinhibition
      of CeM fear output neurons and therefore an increase in fear expression.

PMID- 22972959
TI  - An in vivo investigation of inferior colliculus single neuron responses to
      cochlear nucleus pulse train stimulation.
AB  - The auditory brain stem implant (ABI) is being used clinically to restore hearing
      to patients unable to benefit from a cochlear implant (CI). Speech perception
      outcomes for ABI users are typically poor compared with most CI users. The ABI is
      implanted either on the surface of or penetrating through the cochlear nucleus in
      the auditory brain stem and uses stimulation strategies developed for auditory
      nerve stimulation with a CI. Although the stimulus rate may affect speech
      perception outcomes with current stimulation strategies, no studies have
      systematically investigated the effect of stimulus rate electrophysiologically or
      clinically. We therefore investigated rate response properties and temporal
      response properties of single inferior colliculus (IC) neurons from penetrating
      ABI stimulation using stimulus rates ranging from 100 to 1,600 pulses/s in the
      rat. We found that the stimulus rate affected the proportion of response types,
      thresholds, and dynamic ranges of IC activation. The stimulus rate was also found
      to affect the temporal properties of IC responses, with higher rates providing
      more temporally similar responses to acoustic stimulation. Suppression of neural
      firing and inhibition in IC neurons was also found, with response properties
      varying with the stimulus rate. This study demonstrated that changes in the ABI
      stimulus rate results in significant differences in IC neuron response
      properties. Due to electrophysiological differences, the stimulus rate may also
      change perceptual properties. We suggest that clinical evaluation of the ABI
      stimulus rate should be performed.

PMID- 22972960
TI  - Can proprioceptive training improve motor learning?
AB  - Recent work has investigated the link between motor learning and sensory function
      in arm movement control. A number of findings are consistent with the idea that
      motor learning is associated with systematic changes to proprioception (Haith A,
      Jackson C, Mial R, Vijayakumar S. Adv Neural Inf Process Syst 21: 593-600, 2008;
      Ostry DJ, Darainy M, Mattar AA, Wong J, Gribble PL. J Neurosci 30: 5384-5393,
      2010; Vahdat S, Darainy M, Milner TE, Ostry DJ. J Neurosci 31: 16907-16915,
      2011). Here, we tested whether motor learning could be improved by providing
      subjects with proprioceptive training on a desired hand trajectory. Subjects were
      instructed to reproduce both the time-varying position and velocity of novel,
      complex hand trajectories. Subjects underwent 3 days of training with 90 movement
      trials per day. Active movement trials were interleaved with demonstration
      trials. For control subjects, these interleaved demonstration trials consisted of
      visual demonstration alone. A second group of subjects received visual and
      proprioceptive demonstration simultaneously; this group was presented with the
      same visual stimulus, but, in addition, their limb was moved through the target
      trajectory by a robot using servo control. Subjects who experienced the
      additional proprioceptive demonstration of the desired trajectory showed greater
      improvements during training movements than control subjects who only received
      visual information. This benefit of adding proprioceptive training was seen in
      both movement speed and position error. Interestingly, additional control
      subjects who received proprioceptive guidance while actively moving their arm
      during demonstration trials did not show the same improvement in positional
      accuracy. These findings support the idea that the addition of proprioceptive
      training can augment motor learning, and that this benefit is greatest when the
      subject passively experiences the goal movement.

PMID- 22972961
TI  - Hippocampal neuron firing and local field potentials in the in vitro 4
      aminopyridine epilepsy model.
AB  - Excessive synchronous neuronal activity is a defining feature of epileptic
      activity. We previously characterized the properties of distinct glutamatergic
      and GABAergic transmission-dependent synchronous epileptiform discharges in mouse
      hippocampal slices using the 4-aminopyridine model of epilepsy. In the present
      study, we sought to identify the specific hippocampal neuronal populations that
      initiate and underlie these local field potentials (LFPs). A perforated
      multielectrode array was used to simultaneously record multiunit action potential
      firing and LFPs during spontaneous epileptiform activity. LFPs had distinct
      components based on the initiation site, extent of propagation, and
      pharmacological sensitivity. Individual units, located in different hippocampal
      subregions, fired action potentials during these LFPs. A specific neuron subgroup
      generated sustained action potential firing throughout the various components of
      the LFPs. The activity of this subgroup preceded the LFPs observed in the
      presence of antagonists of ionotropic glutamatergic synaptic transmission. In the
      absence of ionotropic glutamatergic and GABAergic transmission, LFPs disappeared,
      but units with shorter spike duration and high basal firing rates were still
      active. These spontaneously active units had an increased level of activity
      during LFPs and consistently preceded all LFPs recorded before blockade of
      synaptic transmission. Our findings reveal that neuronal subpopulations with
      interneuron properties are likely responsible for initiating synchronous activity
      in an in vitro model of epileptiform discharges.

PMID- 22972963
TI  - The temporal characteristics of Ca2+ entry through L-type and T-type Ca2+
      channels shape exocytosis efficiency in chick auditory hair cells during
      development.
AB  - During development, synaptic exocytosis by cochlear hair cells is first initiated
      by patterned spontaneous Ca(2+) spikes and, at the onset of hearing, by sound
      driven graded depolarizing potentials. The molecular reorganization occurring in
      the hair cell synaptic machinery during this developmental transition still
      remains elusive. We characterized the changes in biophysical properties of
      voltage-gated Ca(2+) currents and exocytosis in developing auditory hair cells of
      a precocial animal, the domestic chick. We found that immature chick hair cells
      (embryonic days 10-12) use two types of Ca(2+) currents to control exocytosis:
      low-voltage-activating, rapidly inactivating (mibefradil sensitive) T-type Ca(2+)
      currents and high-voltage-activating, noninactivating (nifedipine sensitive) L
      type currents. Exocytosis evoked by T-type Ca(2+) current displayed a fast
      release component (RRP) but lacked the slow sustained release component (SRP),
      suggesting an inefficient recruitment of distant synaptic vesicles by this
      transient Ca(2+) current. With maturation, the participation of L-type Ca(2+)
      currents to exocytosis largely increased, inducing a highly Ca(2+) efficient
      recruitment of an RRP and an SRP component. Notably, L-type-driven exocytosis in
      immature hair cells displayed higher Ca(2+) efficiency when triggered by
      prerecorded native action potentials than by voltage steps, whereas similar
      efficiency for both protocols was found in mature hair cells. This difference
      likely reflects a tighter coupling between release sites and Ca(2+) channels in
      mature hair cells. Overall, our results suggest that the temporal characteristics
      of Ca(2+) entry through T-type and L-type Ca(2+) channels greatly influence
      synaptic release by hair cells during cochlear development.

PMID- 22972962
TI  - Regulation of presynaptic calcium in a mammalian synaptic terminal.
AB  - Ca(2+) signaling in synaptic terminals plays a critical role in neurotransmitter
      release and short-term synaptic plasticity. In the present study, we examined the
      role of synaptic Ca(2+) handling mechanisms in the synaptic terminals of
      mammalian rod bipolar cells, neurons that play a pivotal role in the high
      sensitivity vision pathway. We found that mitochondria sequester Ca(2+) under
      conditions of high Ca(2+) load, maintaining intraterminal Ca(2+) near resting
      levels. Indeed, the effect of the mitochondria was so powerful that the ability
      to clamp intraterminal Ca(2+) with a somatically positioned whole cell patch
      pipette was compromised. The plasma membrane Ca(2+)-ATPase (PMCA), but not the
      Na(+)/Ca(2+) exchanger (NCX) or the sarco(endo)plasmic reticulum Ca(2+)-ATPase
      (SERCA), was an important regulator of resting Ca(2+). Furthermore, PMCA
      activity, but not NCX or SERCA activity, was essential for the recovery of Ca(2+)
      levels following depolarization-evoked Ca(2+) entry. Loss of PMCA function was
      also associated with impaired restoration of membrane surface area following
      depolarization-evoked exocytosis. Given its roles in the regulation of
      intraterminal Ca(2+) at rest and after a stimulus-evoked Ca(2+) rise, the PMCA is
      poised to modulate luminance coding and adaptation to background illumination in
      the mammalian rod bipolar cell.

PMID- 22972964
TI  - Startle induces early initiation of classically conditioned postural responses.
AB  - Startling acoustic stimuli (SAS) induce the early release of prepared motor
      responses. The current study used SAS, in conjunction with a classical
      conditioning paradigm, to examine advanced motor preparation of conditioned
      postural responses (PRs). After generalized startle responses were induced,
      standing posture was perturbed in 2 blocks of 15 Conditioning trials, where in
      each trial the onset of a nonstartling auditory cue [i.e., a conditioned stimulus
      (CS)] preceded a leftward support-surface translation. Upon completion of each
      block, a single trial was conducted. After block 1, a CS-Only trial was used to
      induce conditioned PRs in the absence of balance perturbations. After block 2, a
      post-Conditioning Startle trial that involved a CS subsequently followed by a SAS
      was used to examine motor preparation of conditioned PRs. PRs were quantified in
      terms of center of pressure displacements, ankle and hip kinematics, as well as
      surface electromyography of proximal and distal bilateral muscle pairs. Results
      indicated that repeated experience with cued balance perturbations led to PR
      conditioning and, more importantly, motor preparation of PRs. Conditioning was
      evidenced in biomechanical and electromyographic responses observed in CS-Only
      trials, as well as the progressive changes to evoked response parameters during
      repeated Conditioning trials. SAS presented in post-Conditioning Startle trials
      evoked early onsets of biomechanical and electromyographic responses, while
      preserving relative response parameters that were each distinct from generalized
      startle responses. These results provide important insight into both the
      consequences of using cues in dynamic postural control studies and the neural
      mechanisms governing PRs.

PMID- 22972965
TI  - Changes in wrist muscle activity with forearm posture: implications for the study
      of sensorimotor transformations.
AB  - The primate wrist is an ideal model system for studying the reference frames in
      which movements are coded within the central nervous system, as a simple rotation
      of the forearm allows dissociation between extrinsic and body-referenced
      coordinates. Important information regarding coordinate frame transformations has
      been obtained using this system, particularly from studies involving
      extracellular cortical and spinal recordings from monkeys. Because preferred
      directions of muscle use were reported to rotate by less than half of the joint
      rotation, the system was considered to dissociate three reference frames:
      extrinsic (direction of movement in space), muscle (activity of muscles), and
      joint (angle of the wrist joint). However, given the relatively minor changes in
      reported muscle biomechanics with human forearm rotation, the reported
      distinction between joint space and muscle space is surprisingly large. Here, we
      reassessed patterns of wrist muscle activity with changes in forearm posture in
      humans, during an isometric force-aiming task with a device that enabled
      stringent control of the musculoskeletal configuration. Results show that the
      preferred directions for wrist muscle activation closely follow forearm
      orientation (i.e., by 88%). Control experiments confirmed this, whether the hand
      was clamped passively by a device or grasped a handle. Furthermore, the remaining
      12% discrepancy between intended changes in wrist orientation and muscle use also
      occurred for muscle-pulling directions obtained by intramuscular electrical
      stimulation. The findings prompt reconsideration of data based on the previously
      reported dissociation between joint space and muscle space and have critical
      implications for future investigations of sensorimotor transformations and their
      adaptation using the wrist.

PMID- 22972967
TI  - Effects of ankle extensor muscle afferent inputs on hip abductor and adductor
      activity in the decerebrate walking cat.
AB  - Electrical stimulation of the lateral gastrocnemius-soleus (LGS) nerve at group I
      afferent strength leads to adaptations in the amplitude and timing of extensor
      muscle activity during walking in the decerebrate cat. Such afferent feedback in
      the stance leg might result from a delay in stance onset of the opposite leg.
      Concomitant adaptations in hip abductor and adductor activity would then be
      expected to maintain lateral stability and balance until the opposite leg is able
      to support the body. As many hip abductors and adductors are also hip extensors,
      we hypothesized that stimulation of the LGS nerve at group I afferent strength
      would produce increased activation and prolonged burst duration in hip abductor
      and adductor muscles in the premammillary decerebrate walking cat. LGS nerve
      stimulation during the extensor phase of the locomotor cycle consistently
      increased burst amplitude of the gluteus medius and adductor femoris muscles, but
      not pectineus or gracilis. In addition, LGS stimulation prolonged the burst
      duration of both gluteus medius and adductor femoris. Unexpectedly, long-duration
      LGS stimulus trains resulted in two distinct outcomes on the hip abductor and
      adductor bursting pattern: 1) a change of burst duration and timing similar to
      medial gastrocnemius; or 2) to continue rhythmically bursting uninterrupted.
      These results indicate that activation of muscle afferents from ankle extensors
      contributes to the regulation of activity of some hip abductor and adductor
      muscles, but not all. These results have implications for understanding the
      neural control of stability during locomotion, as well as the organization of
      spinal locomotor networks.

PMID- 22972966
TI  - NMDA induces persistent inward and outward currents that cause rhythmic bursting
      in adult rodent motoneurons.
AB  - N-methyl-d-aspartate (NMDA) receptors are of critical importance for locomotion
      in the developing neonatal spinal cord in rats and mice. However, due to profound
      changes in the expression of NMDA receptors in development between the neonatal
      stages and adulthood, it is unclear whether NMDA receptors are still an important
      component of locomotion in the adult rodent spinal cord. To shed light on this
      issue, we have taken advantage of recently developed preparations allowing the
      intracellular recording of adult motoneurons that control the tail in the
      sacrocaudal spinal cord of adult mice and rats. We show that in the adult
      sacrocaudal spinal cord, NMDA induces rhythmic activity recorded on the ventral
      roots, often coordinated from left to right, as in swimming motions with the tail
      (fictive locomotion). The adult motoneurons themselves are intrinsically
      sensitive to NMDA application. That is, when motoneurons are synaptically
      isolated with TTX, NMDA still causes spontaneous bursts of rhythmic activity,
      depending on the membrane potential. We show that these bursts in motoneurons
      depend on an NMDA-mediated persistent inward current and are terminated by the
      progressive activation of a persistent outward current. These results indicate
      that motoneurons, along with the central pattern generator, can actively
      participate in the production of swimminglike locomotor activity in adult
      rodents.

PMID- 22972968
TI  - Health-related quality-of-life findings for the prostate cancer prevention trial.
AB  - BACKGROUND: The Prostate Cancer Prevention Trial (PCPT)-a randomized placebo
      controlled study of the efficacy of finasteride in preventing prostate cancer
      offered the opportunity to prospectively study effects of finasteride and other
      covariates on the health-related quality of life of participants in a multiyear
      trial. METHODS: We assessed three health-related quality-of-life domains
      (measured with the Health Survey Short Form-36: Physical Functioning, Mental
      Health, and Vitality scales) via questionnaires completed by PCPT participants at
      enrollment (3 months before randomization), at 6 months after randomization, and
      annually for 7 years. Covariate data obtained at enrollment from patient
      completed questionnaires were included in our model. Mixed-effects model analyses
      and a cross-sectional presentation at three time points began at 6 months after
      randomization. All statistical tests were two-sided. RESULTS: For the physical
      function outcome (n = 16 077), neither the finasteride main effect nor the
      finasteride interaction with time were statistically significant. The effects of
      finasteride on physical function were minor and accounted for less than a 1-point
      difference over time in Physical Functioning scores (mixed-effect estimate =
      0.07, 95% confidence interval [CI] = -0.28 to 0.42, P = .71). Comorbidities such
      as congestive heart failure (estimate = -5.64, 95% CI = -7.96 to -3.32, P <
      .001), leg pain (estimate = -2.57, 95% CI = -3.04 to -2.10, P < .001), and
      diabetes (estimate = -1.31, 95% CI = -2.04 to -0.57, P < .001) had statistically
      significant negative effects on physical function, as did current smoking
      (estimate = -2.34, 95% CI = -2.97 to -1.71, P < .001) and time on study (estimate
      = -1.20, 95% CI = -1.36 to -1.03, P < .001). Finasteride did not have a
      statistically significant effect on the other two dependent variables, mental
      health and vitality, either in the mixed-effects analyses or in the cross
      sectional analysis at any of the three time points. CONCLUSION: Finasteride did
      not negatively affect SF-36 Physical Functioning, Mental Health, or Vitality
      scores.

PMID- 22972969
TI  - An epidemiological and molecular study of the relationship between smoking, risk
      of nasopharyngeal carcinoma, and Epstein-Barr virus activation.
AB  - BACKGROUND: Elevated levels of antibodies against antigens in the Epstein-Barr
      virus (EBV) lytic phase are important predictive markers for nasopharyngeal
      carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also
      been associated with NPC risk. We hypothesized that some specific lifestyle
      factors induce transformation of EBV from the latent to the lytic stage and
      contribute to NPC occurrence. METHODS: We conducted a case-control study using
      data from male case patients (n = 1316) and control subjects (n = 1571) living in
      Guangdong Province, an area in China at high risk for NPC, to study potential NPC
      risk factors and EBV inducers. Two independent healthy male populations from a
      second high-risk area (n = 1657) and a low-risk area (n = 1961) were also
      included in the analysis of potential EBV inducers using logistic regression
      models. In vitro assays were performed to investigate the effect of cigarette
      smoke extract on EBV activation in two EBV-positive cell lines. All statistical
      tests were two-sided. RESULTS: Smoking was associated with an increased risk of
      NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs
      never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to
      2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV
      seropositivity among the expanded control group and the independent low-risk
      population. In vitro experiments showed that cigarette smoke extract promoted EBV
      replication, induced the expression of the immediate-early transcriptional
      activators Zta and Rta, and increased transcriptional expression levels of BFRF3
      and gp350 in the lytic phase. CONCLUSION: Smoking is not only associated with NPC
      risk in individuals from China but is also associated with EBV seropositivity in
      healthy males and is involved in EBV activation.

PMID- 22972970
TI  - Re: hepatocellular carcinoma risk factors and disease burden in a european
      cohort: a nested case-control study.

PMID- 22972971
TI  - Skeletal complications of bisphosphonate use: what the radiologist should know.
AB  - Bisphosphonates are widely used for prevention of fractures in patients at risk,
      mainly in the presence of osteoporosis and bone metastases. A number of adverse
      effects of prolonged bisphosphonate treatment have emerged. We would like to
      highlight the skeletal complications from which a radiologist may be the first
      healthcare professional to recognise the association with bisphosphonate therapy.
      We illustrate these complications (namely osteonecrosis of the jaw and less well
      known atypical femoral shaft fractures), presenting radiological findings in our
      patients. Recommendations for safer use of bisphosphonates are included in the
      conclusion of our review.

PMID- 22972972
TI  - Radiotherapy physics research in the UK: challenges and proposed solutions.
AB  - In 2011, the Clinical and Translational Radiotherapy Research Working Group
      (CTRad) of the National Cancer Research Institute brought together UK
      radiotherapy physics leaders for a think tank meeting. Following a format that
      CTRad had previously and successfully used with clinical oncologists, 23
      departments were asked to complete a pre-meeting evaluation of their radiotherapy
      physics research infrastructure and the strengths, weaknesses, opportunities and
      threats within their own centre. These departments were brought together with the
      CTRad Executive Group and research funders to discuss the current state of
      radiotherapy physics research, perceived barriers and possible solutions. In this
      Commentary, we summarise the submitted materials, presentations and discussions
      from the meeting and propose an action plan. It is clear that there are
      challenges in both funding and staffing of radiotherapy physics research.
      Programme and project funding streams sometimes struggle to cater for physics-led
      work, and increased representation on research funding bodies would be valuable.
      Career paths for academic radiotherapy physicists need to be examined and an
      academic training route identified within Modernising Scientific Careers; the
      introduction of formal job plans may allow greater protection of research time,
      and should be considered. Improved access to research facilities, including
      research linear accelerators, would enhance research activity and pass on
      developments to patients more quickly; research infrastructure could be
      benchmarked against centres in the UK and abroad. UK National Health Service
      departments wishing to undertake radiotherapy research, with its attendant added
      value for patients, need to develop a strategy with their partner higher
      education institution, and collaboration between departments may provide enhanced
      opportunities for funded research.

PMID- 22972973
TI  - Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids.
AB  - OBJECTIVE: We propose and study a new model aimed at describing the low-dose
      hyper-radiosensitivity phenomenon appearing in the survival curves of different
      cell lines. METHODS: The model uses the induced repair assumption, considering
      that the critical dose at which this mechanism begins to act varies from cell to
      cell in a given population. The model proposed is compared with the linear
      quadratic model and the modified linear-quadratic model, which is commonly used
      in literature and in which the induced repair is taken into account in a
      heuristic way. The survival curve for the MCF-7 line of human breast cancer is
      measured at low absorbed doses and the uncertainties in these doses are estimated
      using thermoluminiscent dosemeters. RESULTS: It is shown that these multicellular
      spheroids present low-dose hyper-radiosensitivity. The new model permits an
      accurate description of the data of two human cell lines (previously published)
      and of the multicellular spheroids of the MCF-7 line here measured. CONCLUSION:
      The model shows enough flexibility to account for data with very different
      characteristics and considers in a faithful way the hypothesis of the repair
      induction.

PMID- 22972974
TI  - Assessing the consistency of bladder filling using an ultrasonic Bladderscan
      device.

PMID- 22972976
TI  - Cystic renal mass in a patient with previous Wilm's tumour.

PMID- 22972977
TI  - Increasing the yield of recombinant thyroid-stimulating hormone-stimulated 2-(18
      fluoride)-flu-2-deoxy-D-glucose positron emission tomography-CT in patients with
      differentiated thyroid carcinoma.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of recombinant
      thyroid-stimulating hormone (rTSH)-stimulated 2-(18-fluoride)-flu-2-deoxy-D
      glucose ((18)F-FDG) positron emission tomography (PET)-CT in detecting recurrence
      in patients with differentiated thyroid cancer. METHODS: Consecutive (18)F-FDG
      PET-CT scans performed with rTSH stimulation between 2007 and 2010 in patients
      with a history of papillary or follicular thyroid carcinoma were reviewed. PET-CT
      findings were correlated with thyroglobulin levels, and histological, clinical
      and radiological follow-up. RESULTS: 58 rTSH PET-CT scans were performed in 47
      patients with a previous thyroidectomy and radioiodine ablation. The only
      indication for PET-CT was a raised thyroglobulin level in 46 of 58 scans, with
      the remainder for characterisation of equivocal radiology or staging. 25 (43%) of
      PET-CT scans were positive for recurrent disease. Histological correlation was
      available for 21 (36%) scans. The overall sensitivity, specificity, positive
      predictive value and negative predictive value were 69%, 76%, 72% and 73%,
      respectively. Median unstimulated thyroglobulin in true-positive scans was 33 ug
      l(-1) and 2.2 ug l(-1) in the remainder (p=0.12). 4 of 35 (11%) patients with
      unstimulated thyroglobulin levels <10 ug l(-1) had true-positive scans. Median
      stimulated thyroglobulin in true-positive scans was 320 ug l(-1), and 10 ug l(-1)
      in the remainder (p=0.046), with no positive scans with a stimulated
      thyroglobulin <8 ug l(-1). PET-CT directly influenced patient management in 17/58
      (29%) scans. CONCLUSION: rTSH PET-CT is a useful imaging technique for detecting
      disease recurrence in patients with iodine-resistant differentiated thyroid
      cancer. Low stimulated thyroglobulin levels are potentially useful in identifying
      patients unlikely to benefit from a PET-CT scan.

PMID- 22972978
TI  - Dual-source, dual-energy multidetector CT for the evaluation of pancreatic
      tumours.
AB  - OBJECTIVE: To investigate the potential diagnostic value of dual-energy CT (DECT)
      with virtual non-enhanced (VNE) and iodine-only images, and to determine the
      optimal mixed ratio of blended images for evaluation of pancreatic diseases.
      METHODS: Multiphasic DECT was performed in 44 patients with focal pancreatic
      disease. DECT was used during the pancreatic and hepatic venous phases, and a
      peak kilovoltage of 120 kVp was used for both non-contrast phases. For
      qualitative analysis of the CT images, two radiologists assessed three image sets
      (VNE, iodine-only and blended images) in order to determine the acceptability of
      VNE in replacing true non-enhanced (TNE) images, the added value of iodine-only
      images and the preferred blending ratio. For quantitative analyses, the CT
      numbers and image noise of the pancreatic parenchyma, lesions, aorta and psoas
      muscle were measured. The contrast-to-noise ratio of the lesion was calculated on
      the pancreatic phase images. The effective radiation dose for DECT and TNE images
      was calculated. Statistical comparisons were made using the Friedman test, the
      Wilcoxon test, the paired t-test and repeated measures of analysis of variation
      with Bonferroni correction for multiple comparisons. RESULTS: The level of
      acceptance of the VNE images in replacing TNE images was 90.9%. Regarding the
      iodine-only images, 50% of the cases were found to have an added value. The
      linear-blended images with a weighting factor of 0.5 were preferred. CONCLUSIONS:
      DECT was able to provide high-quality VNE images that could replace TNE images
      and iodine-only images showing an added value. Blended images with a weighting
      factor of 0.5 were preferred by the reviewers.

PMID- 22972979
TI  - A clinical system for three-dimensional extended-field-of-view ultrasound.
AB  - OBJECTIVE: This work is concerned with the creation of three-dimensional (3D)
      extended-field-of-view ultrasound from a set of volumes acquired using a
      mechanically swept 3D probe. 3D volumes of ultrasound data can be registered by
      attaching a position sensor to the probe; this can be an inconvenience in a
      clinical setting. A position sensor can also cause some misalignment due to
      patient movement and respiratory motion. We propose a combination of three
      degrees-of-freedom image registration and an unobtrusively integrated inertial
      sensor for measuring orientation. The aim of this research is to produce a
      reliable and portable ultrasound system that is able to register 3D volumes
      quickly, making it suitable for clinical use. METHOD: As part of a feasibility
      study we recruited 28 pregnant females attending for routine obstetric scans to
      undergo 3D extended-field-of-view ultrasound. A total of 49 data sets were
      recorded. Each registered data set was assessed for correct alignment of each
      volume by two independent observers. RESULTS: In 77-83% of the data sets more
      than four consecutive volumes registered. The successful registration relies on
      good overlap between volumes and is adversely affected by advancing gestational
      age and foetal movement. CONCLUSION: The development of reliable 3D extended
      field-of-view ultrasound may help ultrasound practitioners to demonstrate the
      anatomical relation of pathology and provide a convenient way to store data.

PMID- 22972980
TI  - Fourth review of the UK national patient dose database.

PMID- 22972983
TI  - Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive
      Hodgkin lymphoma.
AB  - An altered anti-Epstein-Barr virus (EBV) serologic profile preceding diagnosis is
      associated with an increased risk of Hodgkin lymphoma. It is unknown whether this
      atypical pattern predicts Hodgkin lymphoma risk further subdivided by
      determination of EBV in tumor cells. A nested case-control study of 128 incident
      Hodgkin lymphoma cases and 368 matched controls from active-duty military
      personnel with archived serum in the US Department of Defense Serum Repository
      was conducted to determine whether a panel of anti-EBV antibody titers differed
      in EBV(+) and EBV(-) Hodgkin lymphoma. Among 40 EBV(+) Hodgkin lymphoma cases and
      matched controls, statistically significant increased risks were associated with
      elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence
      interval [CI], 1.1-8.7), and an anti-EBNA-1/anti-EBNA-2 antibody ratio <= 1.0
      versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant
      associations were found among 88 EBV(-) Hodgkin lymphoma cases relative to their
      matched controls. In case-case analysis, EBV(+) disease was significantly
      associated with a low anti-EBNA-1/anti-EBNA-2 antibody ratio. This distinctive
      serologic response to EBV latent antigens, indicative of immune dysfunction in
      other clinical settings, is associated with an increased risk of developing
      EBV(+) but not EBV(-) Hodgkin lymphoma.

PMID- 22972984
TI  - Signaling through cannabinoid receptor 2 suppresses murine dendritic cell
      migration by inhibiting matrix metalloproteinase 9 expression.
AB  - Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and
      autoimmune disease and CNS injury models results in significant attenuation of
      clinical disease, and reduction of inflammatory mediators. Previous studies
      reported that CB2R signaling also reduces leukocyte migration. Migration of
      dendritic cells (DCs) to various sites is required for their activation and for
      the initiation of adaptive immune responses. Here, we report for the first time
      that CB2R signaling affects DC migration in vitro and in vivo, primarily through
      the inhibition of matrix metalloproteinase 9 (MMP-9) expression. Reduced MMP-9
      production by DCs results in decreased migration to draining lymph nodes in vivo
      and in vitro in the matrigel migration assay. The effect on Mmp-9 expression is
      mediated through CB2R, resulting in reduction in cAMP levels, subsequent decrease
      in ERK activation, and reduced binding of c-Fos and c-Jun to Mmp-9 promoter
      activator protein 1 sites. We postulate that, by dampening production of MMP-9
      and subsequent MMP-9-dependent DC migration, cannabinoids contribute to resolve
      acute inflammation and to reestablish homeostasis. Selective CB2R agonists might
      be valuable future therapeutic agents for the treatment of chronic inflammatory
      conditions by targeting activated immune cells, including DCs.

PMID- 22972982
TI  - A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in
      megakaryocytes near a MEIS1 binding site.
AB  - We recently identified 68 genomic loci where common sequence variants are
      associated with platelet count and volume. Platelets are formed in the bone
      marrow by megakaryocytes, which are derived from hematopoietic stem cells by a
      process mainly controlled by transcription factors. The homeobox transcription
      factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other
      lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci
      pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In
      one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls
      within a region acting as an alternative promoter that is solely used in
      megakaryocytes, where allelic variation dictates different levels of a shorter
      transcript. The importance of dynamin activity to the latter stages of
      thrombopoiesis was confirmed by the observation that the inhibitor Dynasore
      reduced murine proplatelet for-mation in vitro.

PMID- 22972985
TI  - IFNgammaR signaling mediates alloreactive T-cell trafficking and GVHD.
AB  - The clinical goal of allogeneic hematopoietic stem cell transplantation (allo
      HSCT) is to minimize GVHD while maintaining GvL. Here, we show that interferon
      gamma receptor-deficient (IFNgammaR(-/-)) allogeneic Tconv, which possess normal
      alloreactivity and cytotoxicity, induce significantly less GVHD than wild-type
      (WT) Tconv. This effect is mediated by altered trafficking of IFNgammaR(-/-)
      Tconv to GVHD target organs, especially the gastrointestinal (GI) tract. We show
      that the chemokine receptor CXCR3 is induced via IFNgammaR-mediated signaling and
      partially contributes to the trafficking of WT Tconv to GVHD target organs.
      Indeed, CXCR3(-/-) Tconv recapitulate the reduced GVHD potential of IFNgammaR(-/
      ) Tconv in a minor-mismatched GVHD model. Most importantly, IFNgammaR(-/-) (and
      CXCR3(-/-)) Tconv mediate a robust and beneficial GvL effect. In addition, we
      show that IFNgammaR(-/-) regulatory T cells (Tregs) are fully suppressive in
      vitro although defective in suppressor function in vivo and that WT Tregs
      suppress GVHD in vivo only when allogeneic Tconv produce interferon gamma
      (IFNgamma), suggesting that the IFNgammaR signaling pathway is the major
      mechanism for both Tregs and Tconv to migrate to GVHD target organs. Finally,
      pharmacologic inhibition of IFNgammaR signaling with inhibitors of JAK1/JAK2,
      which are mediators of IFNgammaR signaling, results in the decreased expression
      of CXCR3 and reduced GVHD and improved survival after allo-HSCT and this effect
      is mediated by altered trafficking of Tconv to GVHD target organs.

PMID- 22972986
TI  - Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X
      linked neutropenia by exceeding Aurora B kinase error correction capacity.
AB  - The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA
      WASp) is the cause of X-linked neutropenia and is linked with genomic instability
      and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F
      actin through dysregulated activation of the Arp2/3 complex leading to defects in
      cell division. As WASp has no reported role in cell division, we hypothesized
      that alteration of cell mechanics because of increased F-actin may indirectly
      disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed
      that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all
      phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome
      velocity to the cytoplasmic viscosity revealed that cells compensated for
      increased viscosity by up-regulating force applied to chromosomes and increased
      the density of microtubules at kinetochores. Mitotic abnormalities were because
      of overload of the aurora signaling pathway as subcritical inhibition of Aurora
      in CA-WASp cells caused increased cytokinesis failure, while overexpression
      reduced defects. These findings demonstrate that changes in cell mechanics can
      cause significant mitotic abnormalities leading to genomic instability, and
      highlight the importance of mechanical sensors such as Aurora B in maintaining
      the fidelity of hematopoietic cell division.

PMID- 22972989
TI  - Interpersonal closeness and social reward processing.

PMID- 22972987
TI  - TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial
      cell survival and migration.
AB  - TGF-beta activated kinase 1 (TAK1) is a mediator of various cytokine signaling
      pathways. Germline deficiency of Tak1 causes multiple abnormalities, including
      dilated blood vessels at midgestation. However, the mechanisms by which TAK1
      regulates vessel formation have not been elucidated. TAK1 binding proteins 1 and
      2 (TAB1 and TAB2) are activators of TAK1, but their roles in embryonic TAK1
      signaling have not been determined. In the present study, we characterized mouse
      embryos harboring endothelial-specific deletions of Tak1, Tab1, or Tab2 and found
      that endothelial TAK1 and TAB2, but not TAB1, were critically involved in
      vascular formation. TAK1 deficiency in endothelial cells caused increased cell
      death and vessel regression at embryonic day 10.5 (E10.5). Deletion of TNF
      signaling largely rescued endothelial cell death in TAK1-deficient embryos at
      E10.5. However, embryos deficient in both TAK1 and TNF signaling still exhibited
      dilated capillary networks at E12.5. TAB2 deficiency caused reduced TAK1
      activity, resulting in abnormal capillary blood vessels, similar to the compound
      deficiency of TAK1 and TNF signaling. Ablation of either TAK1 or TAB2 impaired
      cell migration and tube formation. Our results show that endothelial TAK1
      signaling is important for 2 biologic processes in angiogenesis: inhibiting TNF
      dependent endothelial cell death and promoting TNF-independent angiogenic cell
      migration.

PMID- 22972988
TI  - Structural basis of CBP/p300 recruitment in leukemia induction by E2A-PBX1.
AB  - E-proteins are critical transcription factors in B-cell lymphopoiesis. E2A, 1 of
      3 E-protein-encoding genes, is implicated in the induction of acute lymphoblastic
      leukemia through its involvement in the chromosomal translocation 1;19 and
      consequent expression of the E2A-PBX1 oncoprotein. An interaction involving a
      region within the N-terminal transcriptional activation domain of E2A-PBX1,
      termed the PCET motif, which has previously been implicated in E-protein
      silencing, and the KIX domain of the transcriptional coactivator CBP/p300,
      critical for leukemogenesis. However, the structural details of this interaction
      remain unknown. Here we report the structure of a 1:1 complex between PCET motif
      peptide and the KIX domain. Residues throughout the helical PCET motif that
      contact the KIX domain are important for both binding KIX and bone marrow
      immortalization by E2A-PBX1. These results provide molecular insights into E
      protein-driven differentiation of B-cells and the mechanism of E-protein
      silencing, and reveal the PCET/KIX interaction as a therapeutic target for E2A
      PBX1-induced leukemia.

PMID- 22972990
TI  - Toward an efficient and integrative analysis of limited-choice behavioral
      experiments.

PMID- 22972991
TI  - Processing of neuregulin-1 by neuropsin regulates GABAergic neuron to control
      neural plasticity of the mouse hippocampus.
AB  - Protease-mediated signaling is an important modulator of the nervous system.
      However, identifying the specific signaling substrates of such proteases is
      limited by the rapidity with which intermediate substrate forms are cleaved and
      released. Here, a screening method to detect noncleaved enzyme-bound forms was
      developed and used to identify a novel neuropsin/neuregulin-1 (NRG-1) proteolytic
      signaling system, which is specifically localized in the microdomain of synaptic
      cleft, in the mouse hippocampus. The extracellular protease, neuropsin, cleaved
      mature NRG-1 (comprising the extracellular domain of the NRG-1) at three newly
      identified sites to remove the heparin-binding domain of NRG-1. This released the
      ligand moiety from the matrix-glycosaminoglycan pool and enabled it to trigger
      the phosphorylation of NRG-1 receptor, p185 (ErbB4). Proteolysis of mature NRG-1
      by neuropsin led to colocalization of the processed NRG-1 with ErbB4 in
      parvalbumin-positive hippocampal interneurons and consequent phosphorylation of
      tyrosine residues of proteins in the cells. Moreover, neuropsin knock-out mice
      exhibited impairments in Schaffer collateral early phase long-term potentiation,
      and application of the recombinant NRG-1 lacking heparin-binding activity
      reversed the effects through the activation of ErbB4 and GABA(A) receptors. Thus,
      ErbB4 signaling induced by neuropsin-dependent processing of NRG-1 contributes to
      the modulation of synaptic plasticity via regulation of GABAergic transmission.
      This signaling system may be involved in human cognition and mental disorders,
      such as schizophrenia and bipolar disorder, by its dysfunction.

PMID- 22972992
TI  - MEC-17 deficiency leads to reduced alpha-tubulin acetylation and impaired
      migration of cortical neurons.
AB  - Neuronal migration is a fundamental process during the development of the
      cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics
      can be modulated by posttranslational modifications to tubulin subunits.
      Acetylation of alpha-tubulin at lysine 40 is important in regulating microtubule
      properties, and this process is controlled by acetyltransferase and deacetylase.
      MEC-17 is a newly discovered alpha-tubulin acetyltransferase that has been found
      to play a major role in the acetylation of alpha-tubulin in different species in
      vivo. However, the physiological function of MEC-17 during neural development is
      largely unknown. Here, we report that MEC-17 is critical for the migration of
      cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex
      during development. MEC-17 deficiency caused migratory defects in the cortical
      projection neurons and interneurons, and perturbed the transition of projection
      neurons from the multipolar stage to the unipolar/bipolar stage in the
      intermediate zone of the cortex. Furthermore, knockdown of alpha-tubulin
      deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated alpha
      tubulin could reduce the migratory and morphological defects caused by MEC-17
      deficiency in cortical projection neurons. Thus, MEC-17, which regulates the
      acetylation of alpha-tubulin, appears to control the migration and morphological
      transition of cortical neurons. This finding reveals the importance of MEC-17 and
      alpha-tubulin acetylation in cortical development.

PMID- 22972993
TI  - Neural dynamics of choice: single-trial analysis of decision-related activity in
      parietal cortex.
AB  - Previous neurophysiological studies of perceptual decision-making have focused on
      single-unit activity, providing insufficient information about how individual
      decisions are accomplished. For the first time, we recorded simultaneously from
      multiple decision-related neurons in parietal cortex of monkeys performing a
      perceptual decision task and used these recordings to analyze the neural dynamics
      during single trials. We demonstrate that decision-related lateral intraparietal
      area neurons typically undergo gradual changes in firing rate during individual
      decisions, as predicted by mechanisms based on continuous integration of sensory
      evidence. Furthermore, we identify individual decisions that can be described as
      a change of mind: the decision circuitry was transiently in a state associated
      with a different choice before transitioning into a state associated with the
      final choice. These changes of mind reflected in monkey neural activity share
      similarities with previously reported changes of mind reflected in human
      behavior.

PMID- 22972994
TI  - Dynamic estimation of task-relevant variance in movement under risk.
AB  - Humans take into account their own movement variability as well as potential
      consequences of different movement outcomes in planning movement trajectories.
      When variability increases, planned movements are altered so as to optimize
      expected consequences of the movement. Past research has focused on the steady
      state responses to changing conditions of movement under risk. Here, we study the
      dynamics of such strategy adjustment in a visuomotor decision task in which
      subjects reach toward a display with regions that lead to rewards and penalties,
      under conditions of changing uncertainty. In typical reinforcement learning
      tasks, subjects should base subsequent strategy by computing an estimate of the
      mean outcome (e.g., reward) in recent trials. In contrast, in our task, strategy
      should be based on a dynamic estimate of recent outcome uncertainty (i.e.,
      squared error). We find that subjects respond to increased movement uncertainty
      by aiming movements more conservatively with respect to penalty regions, and that
      the estimate of uncertainty they use is well characterized by a weighted average
      of recent squared errors, with higher weights given to more recent trials.

PMID- 22972995
TI  - Rab33a mediates anterograde vesicular transport for membrane exocytosis and axon
      outgrowth.
AB  - Axon outgrowth requires plasma membrane expansion, which results from post-Golgi
      vesicular transport and fusion. However, the molecular mechanisms regulating post
      Golgi vesicular trafficking for membrane expansion and axon outgrowth remain
      unclear. Here, we show that Rab33a expression became upregulated during axon
      outgrowth of cultured rat hippocampal neurons. Rab33a was preferentially
      localized to the Golgi apparatus and to synaptophysin-positive vesicles that are
      transported along the growing axon. Previous studies showed that synaptophysin is
      localized to post-Golgi vesicles transported by fast axonal transport in
      developing neurons. Reduction of Rab33a expression by RNAi (RNA interference)
      inhibited the anterograde transport of synaptophysin-positive vesicles, leading
      to their decrease in axonal tips. Furthermore, this treatment reduced membrane
      fusion of synaptophysin-positive vesicles at the growth cones and inhibited axon
      outgrowth. Overexpression of Rab33a, on the other hand, induced excessive
      accumulation of synaptophysin-positive vesicles and concurrent formation of
      surplus axons. These data suggest that Rab33a participates in axon outgrowth by
      mediating anterograde axonal transport of synaptophysin-positive vesicles and
      their concomitant fusion at the growth cones.

PMID- 22972996
TI  - GluN2D subunit-containing NMDA receptors control tissue plasminogen activator
      mediated spatial memory.
AB  - Tissue plasminogen activator (tPA) is a serine protease with pleiotropic actions
      in the CNS, such as synaptic plasticity and neuronal death. Some effects of tPA
      require its interaction with the GluN1 subunit of the NMDA receptor (NMDAR),
      leading to a potentiation of NMDAR signaling. We have reported previously that
      the pro-neurotoxic effect of tPA is mediated through GluN2D subunit-containing
      NMDARs. Thus, the aim of the present study was to determine whether GluN2D
      subunit-containing NMDARs drive tPA-mediated cognitive functions. To address this
      issue, a strategy of immunization designed to prevent the in vivo interaction of
      tPA with NMDARs and GluN2D-deficient mice were used in a set of behavioral tasks.
      Altogether, our data provide the first evidence that tPA influences spatial
      memory through its preferential interaction with GluN2D subunit-containing
      NMDARs.

PMID- 22972997
TI  - Peroxisome proliferator-activated receptor alpha mediates acute effects of
      palmitoylethanolamide on sensory neurons.
AB  - The amplitude of the depolarization-evoked Ca2+ transient is larger in dorsal
      root ganglion (DRG) neurons from tumor-bearing mice compared with that of neurons
      from naive mice, and the change is mimicked by coculturing DRG neurons with the
      fibrosarcoma cells used to generate the tumors (Khasabova et al., 2007). The
      effect of palmitoylethanolamide (PEA), a ligand for the peroxisome proliferator
      activated receptor alpha (PPARalpha), was determined on the evoked-Ca2+ transient
      in the coculture condition. The level of PEA was reduced in DRG cells from tumor
      bearing mice as well as those cocultured with fibrosarcoma cells. Pretreatment
      with PEA, a synthetic PPARalpha agonist (GW7647), or ARN077, an inhibitor of the
      enzyme that hydrolyzes PEA, acutely decreased the amplitude of the evoked Ca2+
      transient in small DRG neurons cocultured with fibrosarcoma cells. The PPARalpha
      antagonist GW6471 blocked the effect of each. In contrast, the PPARalpha agonist
      was without effect in the control condition, but the antagonist increased the
      amplitude of the Ca2+ transient, suggesting that PPARalpha receptors are
      saturated by endogenous ligand under basal conditions. Effects of drugs on
      mechanical sensitivity in vivo paralleled their effects on DRG neurons in vitro.
      Local injection of ARN077 decreased mechanical hyperalgesia in tumor-bearing
      mice, and the effect was blocked by GW6471. These data support the conclusion
      that the activity of DRG neurons is rapidly modulated by PEA through a PPARalpha
      dependent mechanism. Moreover, agents that increase the activity of PPARalpha may
      provide a therapeutic strategy to reduce tumor-evoked pain.

PMID- 22972998
TI  - Group I mGluR-mediated inhibition of Kir channels contributes to retinal Muller
      cell gliosis in a rat chronic ocular hypertension model.
AB  - Muller cell gliosis, which is characterized by upregulated expression of glial
      fibrillary acidic protein (GFAP), is a universal response in many retinal
      pathological conditions. Whether down-regulation of inward rectifying K+ (Kir)
      channels, which commonly accompanies the enhanced GFAP expression, could
      contribute to Muller cell gliosis is poorly understood. We investigated changes
      of Kir currents, GFAP and Kir4.1 protein expression in Muller cells in a rat
      chronic ocular hypertension (COH) model, and explored the mechanisms underlying
      Muller cell gliosis. We show that Kir currents and Kir4.1 protein expression in
      Muller cells were reduced significantly, while GFAP expression was increased in
      COH rats, and these changes were eliminated by MPEP, a group I metabotropic
      glutamate receptors (mGluR I) subtype mGluR5 antagonist. In normal isolated
      Muller cells, the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG)
      suppressed the Kir currents and the suppression was blocked by MPEP. The DHPG
      effect was mediated by the intracellular Ca2+ -dependent PLC/IP3-ryanodine/PKC
      signaling pathway, but the cAMP-PKA pathway was not involved. Moreover,
      intravitreal injection of DHPG in normal rats induced changes in Muller cells,
      similar to those observed in COH rats. The DHPG-induced increase of GFAP
      expression in Muller cells was obstructed by Ba2+, suggesting the involvement of
      Kir channels. We conclude that overactivation of mGluR5 by excessive
      extracellular glutamate in COH rats could contribute to Muller cell gliosis by
      suppressing Kir channels.

PMID- 22972999
TI  - Gone in 0.6 seconds: the encoding of motor memories depends on recent
      sensorimotor states.
AB  - Real-world tasks often require movements that depend on a previous action or on
      changes in the state of the world. Here we investigate whether motor memories
      encode the current action in a manner that depends on previous sensorimotor
      states. Human subjects performed trials in which they made movements in a
      randomly selected clockwise or counterclockwise velocity-dependent curl force
      field. Movements during this adaptation phase were preceded by a contextual phase
      that determined which of the two fields would be experienced on any given trial.
      As expected from previous research, when static visual cues were presented in the
      contextual phase, strong interference (resulting in an inability to learn either
      field) was observed. In contrast, when the contextual phase involved subjects
      making a movement that was continuous with the adaptation-phase movement, a
      substantial reduction in interference was seen. As the time between the
      contextual and adaptation movement increased, so did the interference, reaching a
      level similar to that seen for static visual cues for delays >600 ms. This
      contextual effect generalized to purely visual motion, active movement without
      vision, passive movement, and isometric force generation. Our results show that
      sensorimotor states that differ in their recent temporal history can engage
      distinct representations in motor memory, but this effect decays progressively
      over time and is abolished by ~600 ms. This suggests that motor memories are
      encoded not simply as a mapping from current state to motor command but are
      encoded in terms of the recent history of sensorimotor states.

PMID- 22973000
TI  - Zebrin-immunopositive and -immunonegative stripe pairs represent functional units
      in the pigeon vestibulocerebellum.
AB  - The cerebellum is a site of complex sensorimotor integration and contains up to
      80% of the neurons in the brain, yet comparatively little is known about the
      organization of sensorimotor systems within the cerebellum. It is known that
      afferent projections and Purkinje cell (PC) response properties are organized
      into sagittal "zones" in the cerebellum. Moreover, the isoenzyme aldolase C [also
      known as zebrin II (ZII)] is heterogeneously expressed in cerebellar PCs such
      that there are sagittal stripes of PCs with high expression (ZII+) interdigitated
      with stripes of little or no expression (ZII-). In the present study, we show how
      the ZII stripes in folium IXcd of the vestibulocerebellum in pigeons are related
      to response properties of PCs. IXcd consists of seven pairs of ZII+/- stripes
      denoted P1+/- (medial) to P7+/- (lateral). Electrophysiological studies have
      shown that vestibulocerebellar PCs respond to particular patterns of optic flow
      resulting from self-motion in three-dimensional space. In our study, we recorded
      optic flow preferences from PCs in IXcd, marked recording locations with
      injections of fluorescent tracer, and subsequently immunoreacted coronal sections
      for ZII. We found that the PCs within a ZII+/- stripe pair all responded best to
      the same pattern of optic flow. That is, a ZII+/- stripe pair forms a functional
      unit in the cerebellum. This is the first demonstration that the function of PCs
      is associated with ZII stripes across the mediolateral extent of an entire
      folium.

PMID- 22973001
TI  - Members of the myocyte enhancer factor 2 transcription factor family
      differentially regulate Bdnf transcription in response to neuronal
      depolarization.
AB  - Transcription of the gene encoding brain-derived neurotropic factor (BDNF) is
      induced in response to a wide variety of extracellular stimuli via the activation
      of a complex array of transcription factors. However, to what degree individual
      transcription factors confer specificity upon the regulation of Bdnf is poorly
      understood. Previous studies have shown that members of the myocyte enhancer
      factor 2 (MEF2) transcription factor family bind a regulatory element upstream of
      Bdnf promoter I and associate with an unknown binding site in Bdnf promoter IV.
      Here we identify calcium-response element 1 as the MEF2 binding site in promoter
      IV of the Bdnf gene and determine the requirements for individual MEF2 family
      members in Bdnf regulation. MEF2A, MEF2C, and MEF2D are all highly expressed in
      embryonic rat cortical neurons; however, only the Mef2c gene encodes an MEF2
      splice variant that lacks the gamma repressor-domain. We find that MEF2C variants
      lacking the gamma-domain are particularly sensitive to activation by membrane
      depolarization, raising the possibility that the MEF2s may differentially
      contribute to activity-regulated gene expression. We find that only knockdown of
      MEF2C significantly impairs membrane depolarization-induced expression of Bdnf
      exon IV. By contrast, knockdown of MEF2D significantly enhanced depolarization
      induced expression of Bdnf exon I. Together, these data show that individual
      members of the MEF2 family of transcription factors differentially regulate the
      expression of Bdnf, revealing a new mechanism that may confer specificity on the
      induction of this biologically important gene.

PMID- 22973002
TI  - Chronic suppression of inositol 1,4,5-triphosphate receptor-mediated calcium
      signaling in cerebellar purkinje cells alleviates pathological phenotype in
      spinocerebellar ataxia 2 mice.
AB  - Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder characterized by
      progressive ataxia. SCA2 results from a poly(Q) (polyglutamine) expansion in the
      cytosolic protein ataxin-2 (Atx2). Cerebellar Purkinje cells (PCs) are primarily
      affected in SCA2, but the cause of PC dysfunction and death in SCA2 is poorly
      understood. In previous studies, we reported that mutant but not wild-type Atx2
      specifically binds the inositol 1,4,5-trisphosphate receptor (InsP(3)R) and
      increases its sensitivity to activation by InsP3. We further proposed that the
      resulting supranormal calcium (Ca2+) release from the PC endoplasmic reticulum
      plays a key role in the development of SCA2 pathology. To test this hypothesis,
      we achieved a chronic suppression of InsP(3)R-mediated Ca2+ signaling by
      adenoassociated virus-mediated expression of the inositol 1,4,5-phosphatase
      (Inpp5a) enzyme (5PP) in PCs of a SCA2 transgenic mouse model. We determined that
      recombinant 5PP overexpression alleviated age-dependent dysfunction in the firing
      pattern of SCA2 PCs. We further discovered that chronic 5PP overexpression also
      rescued age-dependent motor incoordination and PC death in SCA2 mice. Our
      findings further support the important role of supranormal Ca2+ signaling in SCA2
      pathogenesis and suggest that partial inhibition of InsP3-mediated Ca2+ signaling
      could provide therapeutic benefit for the patients afflicted with SCA2 and
      possibly other SCAs.

PMID- 22973003
TI  - Distinct neurogenic potential in the retinal margin and the pars plana of
      mammalian eye.
AB  - Unlike many other vertebrates, a healthy mammalian retina does not grow
      throughout life and lacks a ciliary margin zone capable of actively generating
      new neurons. The isolation of stem-like cells from the ciliary epithelium has led
      to speculation that the mammalian retina and/or surrounding tissues may retain
      neurogenic potential capable of responding to retinal damage. Using genetically
      altered mouse lines with varying degrees of retinal ganglion cell loss, we show
      that the retinal margin responds to ganglion cell loss by prolonging specific
      neurogenic activity, as characterized by increased numbers of Atoh7(LacZ)
      expressing cells. The extent of neurogenic activity correlated with the degree of
      ganglion cell deficiency. In the pars plana, but not the retinal margin, cells
      remain proliferative into adulthood, marking the junction of pars plana and
      retinal margin as a niche capable of producing proliferative cells in the
      mammalian retina and a potential cellular source for retinal regeneration.

PMID- 22973004
TI  - Subcellular synaptic connectivity of layer 2 pyramidal neurons in the medial
      prefrontal cortex.
AB  - Pyramidal neurons in the prefrontal cortex (PFC) are important for the control of
      cognitive and emotional behavior. The medial PFC (mPFC) receives diverse long
      range excitatory inputs from the midline thalamus, contralateral mPFC,
      basolateral amygdala, and ventral hippocampus. While axons from these different
      regions have distinct distributions in the mPFC, their functional connections at
      the cellular and subcellular levels remain unknown. Here, we use optogenetics to
      show that layer 2 pyramidal neurons in acute slices of the mouse mPFC receive
      excitatory inputs from each of these regions. Using a combination of optogenetics
      and two-photon microscopy, we then determine the subcellular properties of these
      inputs. We find that different types of inputs make selective contacts at the
      levels of both dendrites and spines. Using two-photon uncaging, we show that this
      subcellular targeting strongly influences synaptic efficacy in these neurons.
      Together, our results show that functional connectivity is finely tuned, with
      important implications for signal processing in the mPFC.

PMID- 22973005
TI  - Activity-dependent regulation of retinogeniculate signaling by metabotropic
      glutamate receptors.
AB  - Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically
      convey visual information from retina to the neocortex. Activation of
      metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural
      integration in dLGN; however, their direct influence on the primary sensory
      input, namely retinogeniculate afferents, is unknown. In the present study, we
      found that pharmacological or synaptic activation of type 1 mGluRs (mGluR(1)s)
      significantly depresses glutamatergic retinogeniculate excitation in rat
      thalamocortical neurons. Pharmacological activation of mGluR(1)s attenuates
      excitatory synaptic responses in thalamocortical neurons at a magnitude
      sufficient to decrease suprathreshold output of these neurons. The reduction in
      both NMDA and AMPA receptor-dependent synaptic responses results from a
      presynaptic reduction in glutamate release from retinogeniculate terminals. The
      suppression of retinogeniculate synaptic transmission and dampening of
      thalamocortical output was mimicked by tetanic activation of retinogeniculate
      afferent in a frequency-dependent manner that activated mGluR(1)s.
      Retinogeniculate excitatory synaptic transmission was also suppressed by the
      glutamate transport blocker TBOA (dl-threo-beta-benzyloxyaspartic acid),
      suggesting that mGluR(1)s were activated by glutamate spillover. The data
      indicate that presynaptic mGluR(1) contributes to an activity-dependent mechanism
      that regulates retinogeniculate excitation and therefore plays a significant role
      in the thalamic gating of visual information.

PMID- 22973006
TI  - Spatiotemporal reconfiguration of large-scale brain functional networks during
      propofol-induced loss of consciousness.
AB  - Applying graph theoretical analysis of spontaneous BOLD fluctuations in
      functional magnetic resonance imaging (fMRI), we investigated whole-brain
      functional connectivity of 11 healthy volunteers during wakefulness and propofol
      induced loss of consciousness (PI-LOC). After extraction of regional fMRI time
      series from 110 cortical and subcortical regions, we applied a maximum overlap
      discrete wavelet transformation and investigated changes in the brain's intrinsic
      spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico
      cortical and corticocortical connectivity. Decrease of connectivity was
      pronounced in thalamocortical connections, whereas no changes were found for
      connectivity within primary sensory cortices. Graph theoretical analyses revealed
      significant changes in the degree distribution and local organization metrics of
      brain functional networks during PI-LOC: compared with a random network,
      normalized clustering was significantly increased, as was small-worldness.
      Furthermore we observed a profound decline in long-range connections and a
      reduction in whole-brain spatiotemporal integration, supporting a topological
      reconfiguration during PI-LOC. Our findings shed light on the functional
      significance of intrinsic brain activity as measured by spontaneous BOLD signal
      fluctuations and help to understand propofol-induced loss of consciousness.

PMID- 22973007
TI  - MeCP2 phosphorylation is required for modulating synaptic scaling through mGluR5.
AB  - MeCP2 (methyl CpG binding protein 2) is a key player in recognizing methylated
      DNA and interpreting the epigenetic information encoded in different DNA
      methylation patterns. The functional significance of MeCP2 to the mammalian
      nervous system is highlighted by the discovery that mutations in the MECP2 gene
      cause Rett syndrome (RTT), a devastating neurological disease that shares many
      features with autism. Synaptic scaling is a form of non-Hebbian homeostatic
      plasticity that allows neurons to regulate overall excitability in response to
      changes in network neuronal activity levels. While it is known that neuronal
      activity can induce phosphorylation of MeCP2 and that MeCP2 can regulate synaptic
      scaling, the molecular link between MeCP2 phosphorylation and synaptic scaling
      remains undefined. We show here that MeCP2 phosphorylation is specifically
      required for bicuculline-induced synaptic scaling down in mouse hippocampal
      neurons and this phenotype is mediated by mGluR5 (metabotropic glutamate receptor
      5). Our results reveal an important function of MeCP2 in regulating neuronal
      homeostasis and may eventually help us understand how MECP2 mutations cause RTT.

PMID- 22973008
TI  - Control over stress, but not stress per se increases prefrontal cortical
      pyramidal neuron excitability.
AB  - Behavioral control over a stressful event reduces the negative consequences of
      not only that event, but also future stressful events. Plasticity in the
      prelimbic (PL) medial prefrontal cortex is critical to this process, but the
      nature of the changes induced is unknown. We used patch-clamp recording to
      measure the intrinsic excitability of PL pyramidal neurons in acute slices from
      rats exposed to either escapable stress (ES), for which rats had behavioral
      control over tail-shock termination, or inescapable stress (IS) without control.
      Shortly after exposure (2 h) to tail-shock stress, neurons in the ES group had
      larger action potential (AP) amplitude and faster AP rise rate, larger postspike
      afterdepolarization, and reduced membrane time constant. No significant effects
      of IS were observed. We developed a conductance-based computer model using the
      simulation tool NEURON. The computer model simulated the observed changes in the
      ES group with increases in Na+ conductance (gNa) and T-type Ca2+ conductance
      (gCa(T)). The empirical and computational results indicate that behavioral
      control over stress, but not stress itself, increases PL pyramidal neuron
      excitability by increasing intrinsic membrane excitability. It is proposed that
      plasticity of excitability is important to the behavioral effects of controllable
      stressor exposure.

PMID- 22973009
TI  - Integrin dynamics produce a delayed stage of long-term potentiation and memory
      consolidation.
AB  - Memory consolidation theory posits that newly acquired information passes through
      a series of stabilization steps before being firmly encoded. We report here that
      in rat and mouse, hippocampus cell adhesion receptors belonging to the beta1
      integrin family exhibit dynamic properties in adult synapses and that these
      contribute importantly to a previously unidentified stage of consolidation.
      Quantitative dual immunofluorescence microscopy showed that induction of long
      term potentiation (LTP) by theta burst stimulation (TBS) activates beta1
      integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal
      slices. Neutralizing antisera selective for beta1 integrins blocked these
      effects. TBS-induced integrin activation was brief (<7 min) and followed by an
      ~45 min period during which the adhesion receptors did not respond to a second
      application of TBS. Brefeldin A, which blocks integrin trafficking to the plasma
      membrane, prevented the delayed recovery of integrin responses to TBS. beta1
      integrin-neutralizing antisera erased LTP when applied during, but not after, the
      return of integrin responsivity. Similarly, infusions of anti-beta1 into rostral
      mouse hippocampus blocked formation of long-term, object location memory when
      started 20 min after learning but not 40 min later. The finding that beta1
      integrin neutralization was effective in the same time window for slice and
      behavioral experiments strongly suggests that integrin recovery triggers a
      temporally discrete, previously undetected second stage of consolidation for both
      LTP and memory.

PMID- 22973010
TI  - LIS1 deficiency promotes dysfunctional synaptic integration of granule cells
      generated in the developing and adult dentate gyrus.
AB  - Type I lissencephaly, a neuronal migration disorder characterized by cognitive
      disability and refractory epilepsy, is often caused by heterozygous mutations in
      the LIS1 gene. Histopathologies of malformation-associated epilepsies have been
      well described, but it remains unclear whether hyperexcitability is attributable
      to disruptions in neuronal organization or abnormal circuit function. Here, we
      examined the effect of LIS1 deficiency on excitatory synaptic function in the
      dentate gyrus of hippocampus, a region believed to serve critical roles in
      seizure generation and learning and memory. Mice with heterozygous deletion of
      LIS1 exhibited robust granule cell layer dispersion, and adult-born granule cells
      labeled with enhanced green fluorescent protein were abnormally positioned in the
      molecular layer, hilus, and granule cell layer. In whole-cell patch-clamp
      recordings, reduced LIS1 function was associated with greater excitatory synaptic
      input to mature granule cells that was consistent with enhanced release
      probability at glutamatergic synapses. Adult-born granule cells that were
      ectopically positioned in the molecular layer displayed a more rapid functional
      maturation and integration into the synaptic network compared with newborn
      granule cells located in the hilus or granule cell layer or in wild-type
      controls. In a conditional knock-out mouse, induced LIS1 deficiency in adulthood
      also enhanced the excitatory input to granule cells in the absence of neuronal
      disorganization. These findings indicate that disruption of LIS1 has direct
      effects on excitatory synaptic transmission independent of laminar
      disorganization, and the ectopic position of adult-born granule cells within a
      malformed dentate gyrus critically influences their functional maturation and
      integration.

PMID- 22973011
TI  - Notch prosensory effects in the Mammalian cochlea are partially mediated by
      Fgf20.
AB  - Hearing loss is becoming an increasingly prevalent problem affecting more than
      250 million people worldwide. During development, fibroblast growth factors
      (FGFs) are required for inner ear development as well as hair cell formation in
      the mammalian cochlea and thus make attractive therapeutic candidates for the
      regeneration of sensory cells. Previous findings showed that Fgfr1 conditional
      knock out mice exhibited hair cell and support cell formation defects.
      Immunoblocking with Fgf20 antibody in vitro produced a similar phenotype. While
      hair cell differentiation in mice starts at embryonic day (E)14.5, beginning with
      the inner hair cells, Fgf20 expression precedes hair cell differentiation at
      E13.5 in the cochlea. This suggests a potential role for Fgf20 in priming the
      sensory epithelium for hair cell formation. Treatment of explants with a gamma
      secretase inhibitor, DAPT, decreased Fgf20 mRNA, suggesting that Notch is
      upstream of Fgf20. Notch signaling also plays an early role in prosensory
      formation during cochlear development. In this report we show that during
      development, Notch-mediated regulation of prosensory formation in the cochlea
      occurs via Fgf20. Addition of exogenous FGF20 compensated for the block in Notch
      signaling and rescued Sox2, a prosensory marker, and Gfi1, an early hair cell
      marker in explant cultures. We hypothesized that Fgf20 plays a role in
      specification, amplification, or maintenance of Sox2 expression in prosensory
      progenitors of the developing mammalian cochlea.

PMID- 22973012
TI  - Live imaging of targeted cell ablation in Xenopus: a new model to study
      demyelination and repair.
AB  - Live imaging studies of the processes of demyelination and remyelination have so
      far been technically limited in mammals. We have thus generated a Xenopus laevis
      transgenic line allowing live imaging and conditional ablation of myelinating
      oligodendrocytes throughout the CNS. In these transgenic pMBP-eGFP-NTR tadpoles
      the myelin basic protein (MBP) regulatory sequences, specific to mature
      oligodendrocytes, are used to drive expression of an eGFP (enhanced green
      fluorescent protein) reporter fused to the Escherichia coli nitroreductase (NTR)
      selection enzyme. This enzyme converts the innocuous prodrug metronidazole (MTZ)
      to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR
      tadpoles display a graded oligodendrocyte ablation in response to MTZ, which
      depends on the exposure time to MTZ. MTZ-induced cell death was restricted to
      oligodendrocytes, without detectable axonal damage. After cessation of MTZ
      treatment, remyelination proceeded spontaneously, but was strongly accelerated by
      retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR
      line as a novel in vivo model for the study of demyelination/remyelination
      processes and for large-scale screens of therapeutic agents promoting myelin
      repair.

PMID- 22973014
TI  - Transient receptor potential canonical channels regulate the induction of
      cerebellar long-term depression.
AB  - In the cerebellum, synaptic strength at the synapses between parallel fibers and
      Purkinje cells is best known to be modulated via metabotropic glutamate receptor
      1 (mGluR1)-dependent cerebellar long-term depression (LTD). An increase in
      intracellular calcium levels plays an important role in inducing mGluR1-dependent
      cerebellar LTD. Downstream of mGluR1, there are two major sources of calcium:
      transient receptor potential canonical (TRPC) channels and inositol trisphosphate
      receptors (IP(3)R). IP(3)R triggers a calcium release from the intracellular
      calcium store. Here, we show that TRPC channels mediate mGluR1-evoked slow
      currents to regulate cerebellar LTD in Sprague Dawley rats. We found that the
      inhibition of TRPC channels blocks the induction of cerebellar LTD. Moreover, we
      show that processes known to underlie cerebellar LTD induction, such as increases
      in intracellular calcium concentration, the activation of protein kinase C, and
      the internalization of GluR2, are also hindered by blocking TRPC. These results
      suggest that the mGluR1-evoked activation of TRPC channels is required for the
      induction of cerebellar LTD.

PMID- 22973013
TI  - Selective corticospinal tract injury in the rat induces primary afferent fiber
      sprouting in the spinal cord and hyperreflexia.
AB  - The corticospinal tract (CST) has dense contralateral and sparse ipsilateral
      spinal cord projections that converge with proprioceptive afferents on common
      spinal targets. Previous studies in adult rats indicate that the loss of dense
      contralateral spinal CST connections after unilateral pyramidal tract section
      (PTx), which models CST loss after stroke or spinal cord injury, leads to
      outgrowth from the spared side into the affected, ipsilateral, spinal cord. The
      reaction of proprioceptive afferents after this CST injury, however, is not
      known. Knowledge of proprioceptive afferent responses after loss of the CST could
      inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after
      injury. Here, we hypothesize that the loss of the contralateral CST results in a
      reactive increase in muscle afferents from the impaired limb and enhancement of
      their physiological actions within the cervical spinal cord. We found that 10 d
      after PTx, proprioceptive afferents sprout into cervical gray matter regions
      denervated by the loss of CST terminations. Furthermore, VGlut1-positive boutons,
      indicative of group 1A afferent terminals, increased on motoneurons. PTx also
      produced an increase in microglial density within the gray matter regions where
      CST terminations were lost. These anatomical changes were paralleled by reduction
      in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our
      data demonstrate for the first time that selective CST injury induces maladaptive
      afferent fiber plasticity remote from the lesion. Our findings suggest a novel
      structural reaction of proprioceptive afferents to the loss of CST terminations
      and provide insight into mechanisms underlying spasticity.

PMID- 22973015
TI  - Stoichiometry of the human glycine receptor revealed by direct subunit counting.
AB  - The subunit stoichiometry of heteromeric glycine-gated channels determines
      fundamental properties of these key inhibitory neurotransmitter receptors;
      however, the ratio of alpha1- to beta-subunits per receptor remains
      controversial. We used single-molecule imaging and stepwise photobleaching in
      Xenopus oocytes to directly determine the subunit stoichiometry of a glycine
      receptor to be 3alpha1:2beta. This approach allowed us to determine the receptor
      stoichiometry in mixed populations consisting of both heteromeric and homomeric
      channels, additionally revealing the quantitative proportions for the two
      populations.

PMID- 22973016
TI  - To blink or not to blink: fine cognitive tuning of the defensive peripersonal
      space.
AB  - The blink reflex elicited by the electrical stimulation of the median nerve at
      the wrist [hand blink reflex (HBR)] is a subcortical, defensive response that is
      enhanced when the stimulated hand is inside the peripersonal space of the face.
      Such enhancement results from a tonic, top-down modulation of the excitability of
      the brainstem interneurons mediating the HBR. Here we aim to (1) characterize the
      somatotopical specificity of this top-down modulation and investigate its
      dependence on (2) cognitive expectations and (3) the presence of objects
      protecting the face, in healthy humans. Experiment 1 showed that the
      somatotopical specificity of the HBR enhancement is partially homosegmental,
      i.e., it is greater for the HBR elicited by the stimulation of the hand near the
      face compared with the other hand, always kept far from the face. Experiment 2
      showed that the HBR is enhanced only when participants expect to receive stimuli
      on the hand close to the face and is thus strongly dependent on cognitive
      expectations. Experiment 3 showed that the HBR enhancement by hand-face proximity
      is suppressed when a thin wooden screen is placed between the participants' face
      and their hand. Thus, the screen reduces the extension of the defensive
      peripersonal space, so that the hand is never inside the peripersonal space of
      the face, even in the "near" condition. Together, these findings indicate a fine
      somatotopical and cognitive tuning of the excitability of brainstem circuits
      subserving the HBR, whose strength is adjusted depending on the context in a
      purposeful manner.

PMID- 22973017
TI  - The auxiliary subunits Neto1 and Neto2 reduce voltage-dependent inhibition of
      recombinant kainate receptors.
AB  - Kainate receptors can be subject to voltage-dependent block by intracellular
      polyamines, which causes inward rectification of the current-voltage
      relationship. Sensitivity to polyamine block is largely determined by the
      identity of a residue within the pore domain that can be altered through RNA
      editing. This process causes replacement of the encoded glutamine(Q) with a
      positively charged arginine(R), eliminating polyamine inhibition and thus inward
      rectification. In neurons, kainate receptors can associate with the auxiliary
      subunits Neto1 or Neto2. These transmembrane proteins alter the trafficking,
      channel kinetics, and pharmacology of the receptors in a subunit-dependent
      manner. We found that coexpression of Neto subunits with recombinant GluK2(Q)
      kainate receptors greatly reduced inward rectification without altering calcium
      permeability. This effect was separate from modulation of channel kinetics, as
      mutations within the extracellular LDLa domain of the Neto proteins completely
      eliminated their effects on desensitization but only reduced their effects on
      rectification. Conversely, deletion of the intracellular C-terminal domain of
      Neto1 or Neto2 or neutralization of positively charged residues within this
      domain prevented the reduction in rectification but did not alter effects on
      channel kinetics. These results demonstrate new roles for Neto1 and Neto2 in
      regulating kainate receptor function and identify domains within these auxiliary
      subunits important for mediating their effects.

PMID- 22973018
TI  - Distinct information representation and processing for goal-directed behavior in
      the dorsolateral and ventrolateral prefrontal cortex and the dorsal premotor
      cortex.
AB  - Although the lateral prefrontal cortex (lPFC) and dorsal premotor cortex (PMd)
      are thought to be involved in goal-directed behavior, the specific roles of each
      area still remain elusive. To characterize and compare neuronal activity in two
      sectors of the lPFC [dorsal (dlPFC) and ventral (vlPFC)] and the PMd, we designed
      a behavioral task for monkeys to explore the differences in their participation
      in four aspects of information processing: encoding of visual signals, behavioral
      goal retrieval, action specification, and maintenance of relevant information. We
      initially presented a visual object (an instruction cue) to instruct a behavioral
      goal (reaching to the right or left of potential targets). After a subsequent
      delay, a choice cue appeared at various locations on a screen, and the animals
      could specify an action to achieve the behavioral goal. We found that vlPFC
      neurons amply encoded object features of the instruction cues for behavioral goal
      retrieval and, subsequently, spatial locations of the choice cues for specifying
      the actions. By contrast, dlPFC and PMd neurons rarely encoded the object
      features, although they reflected the behavioral goals throughout the delay
      period. After the appearance of the choice cues, the PMd held information for
      action throughout the specification and preparation of reaching movements.
      Remarkably, lPFC neurons represented information for the behavioral goal
      continuously, even after the action specification as well as during its
      execution. These results indicate that area-specific representation and
      information processing at progressive stages of the perception-action
      transformation in these areas underlie goal-directed behavior.

PMID- 22973019
TI  - Transdifferentiation of glioblastoma stem-like cells into mural cells drives
      vasculogenic mimicry in glioblastomas.
AB  - Recent evidence has shown that glioblastoma stem-like cells (GSCs) can
      transdifferentiate into endothelial cells and vascular-like tumor cells. The
      latter pattern of vascularization indicates an alternative microvascular
      circulation known as vasculogenic mimicry (VM). However, it remains to be
      clarified how the GSC-driven VM makes a significant contribution to tumor
      vasculature. Here, we investigated 11 cases of glioblastomas and found that most
      of them consisted of blood-perfused vascular channels that coexpress mural cell
      markers smooth muscle alpha-actin and platelet-derived growth factor receptor
      beta, epidermal growth factor receptor, and vascular endothelial growth factor
      receptor 2 (Flk-1), but not CD31 or VE-cadherin. This microvasculature coexisted
      with endothelial cell-associated vessels. GSCs derived from patients with
      glioblastomas developed vigorous mural cell-associated vascular channels but few
      endothelial cell vessels in orthotopic animal models. Suppression of Flk-1
      activity and gene expression abrogated GSC transdifferentiation and
      vascularization in vitro, and inhibited VM in animal models. This study
      establishes mural-like tumor cells differentiated from GSCs as a significant
      contributor to microvasculature of glioblastoma and points to Flk-1 as a
      potential target for therapeutic intervention that could complement current anti
      angiogenic treatment.

PMID- 22973020
TI  - Genetic ablation of hypocretin neurons alters behavioral state transitions in
      zebrafish.
AB  - Sleep is an essential biological need of all animals studied to date. The sleep
      disorder narcolepsy is characterized by excessive daytime sleepiness,
      fragmentation of nighttime sleep, and cataplexy. Narcolepsy is caused by
      selective degeneration of hypothalamic hypocretin/orexin (HCRT) neurons. In
      mammals, HCRT neurons primarily regulate the sleep/wake cycle, feeding, reward
      seeking, and addiction. The role of HCRT neurons in zebrafish is implicated in
      both sleep and wake regulation. We established a transgenic zebrafish model
      enabling inducible ablation of HCRT neurons and used these animals to understand
      the function of HCRT neurons and narcolepsy. Loss of HCRT neurons increased the
      expression of the HCRT receptor (hcrtr). Behavioral assays revealed that HCRT
      neuron-ablated larvae had normal locomotor activity, but demonstrated an increase
      in sleep time during the day and an increased number of sleep/wake transitions
      during both day and night. Mild sleep disturbance reduced sleep and increased c
      fos expression in HCRT neuron-ablated larvae. Furthermore, ablation of HCRT
      neurons altered the behavioral response to external stimuli. Exposure to light
      during the night decreased locomotor activity of wild-type siblings, but induced
      an opposite response in HCRT neuron-ablated larvae. Sound stimulus during the day
      reduced the locomotor activity of wild-type sibling larvae, while HCRT neuron
      ablated larvae demonstrated a hyposensitive response. This study establishes
      zebrafish as a model for narcolepsy, and indicating a role of HCRT neurons in
      regulation of sleep/wake transitions during both day and night. Our results
      further suggest a key role of HCRT neurons in mediating behavioral state
      transitions in response to external stimuli.

PMID- 22973021
TI  - Activation of neuronal NMDA receptors induces superoxide-mediated oxidative
      stress in neighboring neurons and astrocytes.
AB  - Excitotoxic neuronal death is mediated in part by NMDA receptor-induced
      activation of NOX2, an enzyme that produces superoxide and resultant oxidative
      stress. It is not known, however, whether the superoxide is generated in the
      intracellular space, producing oxidative stress in the neurons responding to NMDA
      receptor activation, or in the extracellular space, producing oxidative stress in
      neighboring cells. We evaluated these alternatives by preparing cortical neuron
      cultures from p47(phox-/-) mice, which are unable to form a functional NOX2
      complex, and transfecting the cultures at low density with GFP-tagged p47(phox)
      to reconstitute NOX2 activity in widely scattered neurons. NMDA exposure did not
      induce oxidative stress or cell death in the nontransfected, p47-phox(-/-)
      cultures, but did produce oxidative stress and neuronal death in neurons
      surrounding the transfected, NOX2-competent neurons. This cell-to-cell spread of
      NMDA-induced oxidative injury was blocked by coincubation with either superoxide
      dismutase or the anion channel blocker 4'-diisothiocyanostilbene-2,2'
      disulphonate, confirming superoxide anion as the mediating oxidant. In neurons
      plated on a preexisting astrocyte layer, NMDA induced oxidative stress in both
      the neurons and the astrocytes, and this was also prevented by superoxide
      dismutase. These findings show that activation of NMDA receptors on one neuron
      can lead to oxidative stress and cell death in neighboring neurons and astrocytes
      by a process involving the extracellular release of superoxide by NOX2.

PMID- 22973022
TI  - Reovirus uses multiple endocytic pathways for cell entry.
AB  - Entry of reovirus virions has been well studied in several tissue culture
      systems. After attachment to junctional adhesion molecule A (JAM-A), virions
      undergo clathrin-mediated endocytosis followed by proteolytic disassembly of the
      capsid and penetration to the cytoplasm. However, during in vivo infection of the
      intestinal tract, and likely in the tumor microenvironment, capsid proteolysis
      (uncoating) is initiated extracellularly. We used multiple approaches to
      determine if uncoated reovirus particles, called intermediate subviral particles
      (ISVPs), enter cells by directly penetrating the limiting membrane or if they
      take advantage of endocytic pathways to establish productive infection. We found
      that entry and infection by reovirus ISVPs was inhibited by dynasore, an
      inhibitor of dynamin-dependent endocytosis, as well as by genistein and dominant
      negative caveolin-1, which block caveolar endocytosis. Inhibition of caveolar
      endocytosis also reduced infection by reovirus virions. Extraction of membrane
      cholesterol with methyl-beta-cyclodextrin inhibited infection by virions but had
      no effect when infection was initiated with ISVPs. We found this pathway to be
      independent of both clathrin and caveolin. Together, these data suggest that
      reovirus virions can use both dynamin-dependent and dynamin-independent endocytic
      pathways during cell entry, and they reveal that reovirus ISVPs can take
      advantage of caveolar endocytosis to establish productive infection.

PMID- 22973023
TI  - Differential clade-specific HLA-B*3501 association with HIV-1 disease outcome is
      linked to immunogenicity of a single Gag epitope.
AB  - The strongest genetic influence on immune control in HIV-1 infection is the HLA
      class I genotype. Rapid disease progression in B-clade infection has been linked
      to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA
      B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these
      studies we first demonstrated that whereas HLA-B*3501 is associated with a high
      viral set point in two further B-clade-infected cohorts, in Japan and Mexico,
      this association does not hold in two large C-clade-infected African cohorts. We
      tested the hypothesis that clade-specific differences in HLA associations with
      disease outcomes may be related to distinct targeting of critical CD8(+) T-cell
      epitopes. We observed that only one epitope was significantly targeted
      differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions
      253 to 262) (P = 2 * 10(-5)). In common with two other HLA-B*3501-restricted
      epitopes, in Gag and Nef, that were not targeted differentially, a response
      toward NY10 was associated with a significantly lower viral set point.
      Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E
      polymorphism present in ~90% of B-clade sequences, which critically reduces
      recognition of the Gag NY10 epitope. These data suggest that in spite of any
      inherent HLA-linked T-cell receptor repertoire differences that may exist,
      maximizing the breadth of the Gag-specific CD8(+) T-cell response, by the
      addition of even a single epitope, may be of overriding importance in achieving
      immune control of HIV infection. This distinction is of direct relevance to
      development of vaccines designed to optimize the anti-HIV CD8(+) T-cell response
      in all individuals, irrespective of HLA type.

PMID- 22973024
TI  - Amino acid residue-specific neutralization and nonneutralization of hepatitis C
      virus by monoclonal antibodies to the E2 protein.
AB  - Antibodies to epitopes in the E2 protein of hepatitis C virus (HCV) reduce the
      viral infectivity in vivo and in vitro. However, the virus can persist in
      patients in the presence of neutralizing antibodies. In this study, we generated
      a panel of monoclonal antibodies that bound specifically to the region between
      residues 427 and 446 of the E2 protein of HCV genotype 1a, and we examined their
      capacity to neutralize HCV in a cell culture system. Of the four monoclonal
      antibodies described here, two were able to neutralize the virus in a genotype 1a
      specific manner. The other two failed to neutralize the virus. Moreover, one of
      the nonneutralizing antibodies could interfere with the neutralizing activity of
      a chimpanzee polyclonal antibody at E2 residues 412 to 426, as it did with an HCV
      specific immune globulin preparation, which was derived from the pooled plasma of
      chronic hepatitis C patients. Mapping the epitope-paratope contact interfaces
      revealed that these functionally distinct antibodies shared binding specificity
      for key amino acid residues, including W(437), L(438), L(441), and F(442), within
      the same epitope of the E2 protein. These data suggest that the effectiveness of
      antibody-mediated neutralization of HCV could be deduced from the interplay
      between an antibody and a specific set of amino acid residues. Further
      understanding of the molecular mechanisms of antibody-mediated neutralization and
      nonneutralization should provide insights for designing a vaccine to control HCV
      infection in vivo.

PMID- 22973025
TI  - Rapid transepithelial transport of prions following inhalation.
AB  - Prion infection and pathogenesis are dependent on the agent crossing an
      epithelial barrier to gain access to the recipient nervous system. Several routes
      of infection have been identified, but the mechanism(s) and timing of in vivo
      prion transport across an epithelium have not been determined. The hamster model
      of nasal cavity infection was used to determine the temporal and spatial
      parameters of prion-infected brain homogenate uptake following inhalation and to
      test the hypothesis that prions cross the nasal mucosa via M cells. A small drop
      of infected or uninfected brain homogenate was placed below each nostril, where
      it was immediately inhaled into the nasal cavity. Regularly spaced tissue
      sections through the entire extent of the nasal cavity were processed
      immunohistochemically to identify brain homogenate and the disease-associated
      isoform of the prion protein (PrP(d)). Infected or uninfected brain homogenate
      was identified adhering to M cells, passing between cells of the nasal mucosa,
      and within lymphatic vessels of the nasal cavity at all time points examined.
      PrP(d) was identified within a limited number of M cells 15 to 180 min following
      inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue
      (NALT). While these results support M cell transport of prions, larger amounts of
      infected brain homogenate were transported paracellularly across the respiratory,
      olfactory, and follicle-associated epithelia of the nasal cavity. These results
      indicate that prions can immediately cross the nasal mucosa via multiple routes
      and quickly enter lymphatics, where they can spread systemically via lymph
      draining the nasal cavity.

PMID- 22973026
TI  - MicroRNAs and unusual small RNAs discovered in Kaposi's sarcoma-associated
      herpesvirus virions.
AB  - It is widely held that any given virus uses only one type of nucleic acid for
      genetic information storage. However, this consensus has been challenged slightly
      by several recent studies showing that many RNA species are present within a
      range of DNA viruses that include Kaposi's sarcoma-associated herpesvirus (KSHV).
      RNAs extracted from purified DNA virus particles exhibit great diversity in terms
      of length, abundance, temporal expression, cellular localization, and coding
      capacity during viral infection. In addition to known RNA species, the current
      study showed that small regulatory RNAs were present in KSHV virions. A large
      number of viral and cellular microRNAs (miRNAs), as well as unusual small RNAs
      (usRNAs), were detected in KSHV virions by using deep sequencing. Both viral and
      host miRNAs detected in small RNAs extracted from KSHV virions were further shown
      to colocalize with KSHV virions directly by in situ hybridization (ISH)-electron
      microscopy (EM) (ISH-EM). Some of these miRNAs were differentially present in the
      host cells and KSHV virions, suggesting that they are not randomly present in
      KSHV virions. The virional miRNAs could be transported into host cells, and they
      are biologically functional during de novo viral infection. Our study revealed
      miRNAs and usRNAs as a novel group of components in KSHV virions.

PMID- 22973027
TI  - Gamma interferon (IFN-gamma) receptor restricts systemic dengue virus replication
      and prevents paralysis in IFN-alpha/beta receptor-deficient mice.
AB  - We previously reported that mice lacking alpha/beta and gamma interferon
      receptors (IFN-alpha/betaR and -gammaR) uniformly exhibit paralysis following
      infection with the dengue virus (DENV) clinical isolate PL046, while only a
      subset of mice lacking the IFN-gammaR alone and virtually no mice lacking the IFN
      alpha/betaR alone develop paralysis. Here, using a mouse-passaged variant of
      PL046, strain S221, we show that in the absence of the IFN-alpha/betaR, signaling
      through the IFN-gammaR confers approximately 140-fold greater resistance against
      systemic vascular leakage-associated dengue disease and virtually complete
      protection from dengue-induced paralysis. Viral replication in the spleen was
      assessed by immunohistochemistry and flow cytometry, which revealed a reduction
      in the number of infected cells due to IFN-gammaR signaling by 2 days after
      infection, coincident with elevated levels of IFN-gamma in the spleen and serum.
      By 4 days after infection, IFN-gammaR signaling was found to restrict DENV
      replication systemically. Clearance of DENV, on the other hand, occurred in the
      absence of IFN-gammaR, except in the central nervous system (CNS) (brain and
      spinal cord), where clearance relied on IFN-gamma from CD8(+) T cells. These
      results demonstrate the roles of IFN-gammaR signaling in protection from initial
      systemic and subsequent CNS disease following DENV infection and demonstrate the
      importance of CD8(+) T cells in preventing DENV-induced CNS disease.

PMID- 22973028
TI  - Authentic in vitro replication of two tombusviruses in isolated mitochondrial and
      endoplasmic reticulum membranes.
AB  - Replication of plus-stranded RNA viruses takes place on membranous structures
      derived from various organelles in infected cells. Previous works with Tomato
      bushy stunt tombusvirus (TBSV) revealed the recruitment of either peroxisomal or
      endoplasmic reticulum (ER) membranes for replication. In case of Carnation
      Italian ringspot tombusvirus (CIRV), the mitochondrial membranes supported CIRV
      replication. In this study, we developed ER and mitochondrion-based in vitro
      tombusvirus replication assays. Using purified recombinant TBSV and CIRV
      replication proteins, we showed that TBSV could use the purified yeast ER and
      mitochondrial preparations for complete viral RNA replication, while CIRV
      preferentially replicated in the mitochondrial membranes. The viral RNA became
      partly RNase resistant after ~40 to 60 min of incubation in the purified ER and
      mitochondrial preparations, suggesting that assembly of TBSV and CIRV replicases
      could take place in the purified ER and mitochondrial membranes in vitro. Using
      chimeric and heterologous combinations of replication proteins, we showed that
      multiple domains within the replication proteins are involved in determining the
      efficiency of tombusvirus replication in the two subcellular membranes.
      Altogether, we demonstrated that TBSV is less limited while CIRV is more
      restricted in utilizing various intracellular membranes for replication. Overall,
      the current work provides evidence that tombusvirus replication could occur in
      vitro in isolated subcellular membranes, suggesting that tombusviruses have the
      ability to utilize alternative organellar membranes during infection that could
      increase the chance of mixed virus replication and rapid evolution during
      coinfection.

PMID- 22973029
TI  - Suppression of viral RNA binding and the assembly of infectious hepatitis C virus
      particles in vitro by cyclophilin inhibitors.
AB  - Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable
      component of the HCV replication and assembly machineries. Although its precise
      mechanism of action is not yet clear, current evidence indicates that its
      structure and function are regulated by the cellular peptidylprolyl isomerase
      cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of
      NS5A, in a distributed fashion, and modulates the structure of the disordered
      domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA)
      and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse
      genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs
      inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in
      addition to their well-documented inhibitory effect on RNA replication. Although
      the interaction between NS5A and other viral proteins is not affected by CPIs,
      RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is
      significantly inhibited by CPI treatment, and sensitivity of RNA binding is
      correlated with previously characterized CyPA dependence or CsA sensitivity of
      HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic
      and a full-length replicon of JFH-1 was due, at least in part, to an additional
      role that CyPA plays in HCV assembly, a conclusion that is supported by
      experiments with the clinical CPI alisporivir. The host-directed nature and the
      ability to interfere with more than one step in the HCV life cycle may result in
      a higher genetic barrier to resistance for this class of HCV inhibitors.

PMID- 22973030
TI  - Characterization of the genome, proteome, and structure of yersiniophage phiR1
      37.
AB  - The bacteriophage vB_YecM-phiR1-37 (phiR1-37) is a lytic yersiniophage that can
      propagate naturally in different Yersinia species carrying the correct
      lipopolysaccharide receptor. This large-tailed phage has deoxyuridine (dU)
      instead of thymidine in its DNA. In this study, we determined the genomic
      sequence of phage phiR1-37, mapped parts of the phage transcriptome,
      characterized the phage particle proteome, and characterized the virion structure
      by cryo-electron microscopy and image reconstruction. The 262,391-bp genome of
      phiR1-37 is one of the largest sequenced phage genomes, and it contains 367
      putative open reading frames (ORFs) and 5 tRNA genes. Mass-spectrometric analysis
      identified 69 phage particle structural proteins with the genes scattered
      throughout the genome. A total of 269 of the ORFs (73%) lack homologues in
      sequence databases. Based on terminator and promoter sequences identified from
      the intergenic regions, the phage genome was predicted to consist of 40 to 60
      transcriptional units. Image reconstruction revealed that the phiR1-37 capsid
      consists of hexameric capsomers arranged on a T=27 lattice similar to the
      bacteriophage phiKZ. The tail of phiR1-37 has a contractile sheath. We conclude
      that phage phiR1-37 is a representative of a novel phage type that carries the dU
      containing genome in a phiKZ-like head.

PMID- 22973031
TI  - The crystal structure of a coxsackievirus B3-RD variant and a refined 9-angstrom
      cryo-electron microscopy reconstruction of the virus complexed with decay
      accelerating factor (DAF) provide a new footprint of DAF on the virus surface.
AB  - The coxsackievirus-adenovirus receptor (CAR) and decay-accelerating factor (DAF)
      have been identified as cellular receptors for coxsackievirus B3 (CVB3). The
      first described DAF-binding isolate was obtained during passage of the prototype
      strain, Nancy, on rhabdomyosarcoma (RD) cells, which express DAF but very little
      CAR. Here, the structure of the resulting variant, CVB3-RD, has been solved by X
      ray crystallography to 2.74 A, and a cryo-electron microscopy reconstruction of
      CVB3-RD complexed with DAF has been refined to 9.0 A. This new high-resolution
      structure permits us to correct an error in our previous view of DAF-virus
      interactions, providing a new footprint of DAF that bridges two adjacent
      protomers. The contact sites between the virus and DAF clearly encompass CVB3-RD
      residues recently shown to be required for binding to DAF; these residues
      interact with DAF short consensus repeat 2 (SCR2), which is known to be essential
      for virus binding. Based on the new structure, the mode of the DAF interaction
      with CVB3 differs significantly from the mode reported previously for DAF binding
      to echoviruses.

PMID- 22973032
TI  - The NS1 protein of influenza A virus interacts with cellular processing bodies
      and stress granules through RNA-associated protein 55 (RAP55) during virus
      infection.
AB  - The nonstructural protein (NS1) of influenza A virus performs multiple functions
      in the virus life cycle. Proteomic screening for cellular proteins which interact
      with NS1 identified the cellular protein RAP55, which is one of the components of
      cellular processing bodies (P-bodies) and stress granules. To verify whether NS1
      interacts with cellular P-bodies, interactions between NS1, RAP55, and other P
      body-associated proteins (Ago1, Ago2, and DCP1a) were confirmed using
      coimmunoprecipitation and cellular colocalization assays. Overexpression of RAP55
      induced RAP55-associated stress granule formation and suppressed virus
      replication. Knockdown of RAP55 with small interfering RNA (siRNA) or expression
      of a dominant-negative mutant RAP55 protein with defective interaction with P
      bodies blocked NS1 colocalization to P-bodies in cells. Expression of NS1
      inhibited RAP55 expression and formation of RAP55-associated P-bodies/stress
      granules. The viral nucleoprotein (NP) was found to be targeted to stress
      granules in the absence of NS1 but localized to P-bodies when NS1 was
      coexpressed. Restriction of virus replication via P-bodies occurred in the early
      phases of infection, as the number of RAP55-associated P-bodies in cells
      diminished over the course of virus infection. NS1 interaction with RAP55
      associated P-bodies/stress granules was associated with RNA binding and mediated
      via a protein kinase R (PKR)-interacting viral element. Mutations introduced into
      either RNA binding sites (R38 and K41) or PKR interaction sites (I123, M124,
      K126, and N127) caused NS1 proteins to lose the ability to interact with RAP55
      and to inhibit stress granules. These results reveal an interplay between virus
      and host during virus replication in which NP is targeted to P-bodies/stress
      granules while NS1 counteracts this host restriction mechanism.

PMID- 22973033
TI  - Deletion of specific immune-modulatory genes from modified vaccinia virus Ankara
      based HIV vaccines engenders improved immunogenicity in rhesus macaques.
AB  - Modified vaccinia virus Ankara (MVA) is a safe, attenuated orthopoxvirus that is
      being developed as a vaccine vector but has demonstrated limited immunogenicity
      in several early-phase clinical trials. Our objective was to rationally improve
      the immunogenicity of MVA-based HIV/AIDS vaccines via the targeted deletion of
      specific poxvirus immune-modulatory genes. Vaccines expressing codon-optimized
      HIV subtype C consensus Env and Gag antigens were generated from MVA vector
      backbones that (i) harbor simultaneous deletions of four viral immune-modulatory
      genes, encoding an interleukin-18 (IL-18) binding protein, an IL-1beta receptor,
      a dominant negative Toll/IL-1 signaling adapter, and CC-chemokine binding protein
      (MVADelta4-HIV); (ii) harbor a deletion of an additional (fifth) viral gene,
      encoding uracil-DNA glycosylase (MVADelta5-HIV); or (iii) represent the parental
      MVA backbone as a control (MVA-HIV). We performed head-to-head comparisons of the
      cellular and humoral immune responses that were elicited by these vectors during
      homologous prime-boost immunization regimens utilizing either high-dose (2 *
      10(8) PFU) or low-dose (1 * 10(7) PFU) intramuscular immunization of rhesus
      macaques. At all time points, a majority of the HIV-specific T cell responses,
      elicited by all vectors, were directed against Env, rather than Gag,
      determinants, as previously observed with other vector systems. Both modified
      vectors elicited up to 6-fold-higher frequencies of HIV-specific CD8 and CD4 T
      cell responses and up to 25-fold-higher titers of Env (gp120)-specific binding
      (nonneutralizing) antibody responses that were relatively transient in nature.
      While the correlates of protection against HIV infection remain incompletely
      defined, our results indicate that the rational deletion of specific genes from
      MVA vectors can positively alter their cellular and humoral immunogenicity
      profiles in nonhuman primates.

PMID- 22973034
TI  - Dynamics of memory B-cell populations in blood, lymph nodes, and bone marrow
      during antiretroviral therapy and envelope boosting in simian immunodeficiency
      virus SIVmac251-infected rhesus macaques.
AB  - Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection
      causes B-cell dysregulation and the loss of memory B cells in peripheral blood
      mononuclear cells (PBMC). These effects are not completely reversed by
      antiretroviral treatment (ART). To further elucidate B-cell changes during
      chronic SIV infection and treatment, we investigated memory B-cell subpopulations
      and plasma cells/plasmablasts (PC/PB) in blood, bone marrow, and lymph nodes of
      rhesus macaques during ART and upon release from ART. Macaques previously
      immunized with SIV recombinants and the gp120 protein were included to assess the
      effects of prior vaccination. ART was administered for 11 weeks, with or without
      gp120 boosting at week 9. Naive and resting, activated, and tissue-like memory B
      cells and PC/PB were evaluated by flow cytometry. Antibody-secreting cells (ASC)
      and serum antibody titers were assessed. No lasting changes in B-cell memory
      subpopulations occurred in bone marrow and lymph nodes, but significant decreases
      in numbers of activated memory B cells and increases in numbers of tissue-like
      memory B cells persisted in PBMC. Macaque PC/PB were found to be either CD27(+)
      or CD27(-) and therefore were defined as CD19(+) CD38(hi) CD138(+). The numbers
      of these PC/PB were transiently increased in both PBMC and bone marrow following
      gp120 boosting of the unvaccinated and vaccinated macaque groups. Similarly, ASC
      numbers in PBMC and bone marrow of the two macaque groups also transiently
      increased following envelope boosting. Nevertheless, serum binding titers against
      SIVgp120 remained unchanged. Thus, even during chronic SIV infection, B cells
      respond to antigen, but long-term memory does not develop, perhaps due to
      germinal center destruction. Earlier and/or prolonged treatment to allow the
      generation of virus-specific long-term memory B cells should benefit
      ART/therapeutic vaccination regimens.

PMID- 22973035
TI  - Broadly neutralizing antibodies developed by an HIV-positive elite neutralizer
      exact a replication fitness cost on the contemporaneous virus.
AB  - Approximately 1% of those infected with HIV-1 develop broad and potent serum
      cross-neutralizing antibody activities. It is unknown whether or not the
      development of such immune responses affects the replication of the
      contemporaneous autologous virus. Here, we defined a pathway of autologous viral
      escape from contemporaneous potent and broad serum neutralizing antibodies
      developed by an elite HIV-1-positive (HIV-1(+)) neutralizer. These antibodies
      potently neutralize diverse isolates from different clades and target primarily
      the CD4-binding site (CD4-BS) of the viral envelope glycoprotein. Viral escape
      required mutations in the viral envelope glycoprotein which limited the
      accessibility of the CD4-binding site to the autologous broadly neutralizing anti
      CD4-BS antibodies but which allowed the virus to infect cells by utilizing CD4
      receptors on their surface. The acquisition of neutralization resistance,
      however, resulted in reduced cell entry potential and slower viral replication
      kinetics. Our results indicate that in vivo escape from autologous broadly
      neutralizing antibodies exacts fitness costs to HIV-1.

PMID- 22973036
TI  - A species-specific amino acid difference in the macaque CD4 receptor restricts
      replication by global circulating HIV-1 variants representing viruses from recent
      infection.
AB  - HIV-1 replicates poorly in macaque cells, and this had hindered the advancement
      of relevant nonhuman primate model systems for HIV-1 infection and pathogenesis.
      Several host restriction factors have been identified that contribute to this
      species-specific restriction to HIV-1 replication, but these do not fully explain
      the poor replication of most strains of HIV-1 in macaque cells. Only select HIV-1
      envelope variants, typically those derived from viruses that have been adapted in
      cell culture, result in infectious chimeric SIVs encoding HIV-1 envelope (SHIVs).
      Here we demonstrate that most circulating HIV-1 variants obtained directly from
      infected individuals soon after virus acquisition do not efficiently mediate
      entry using the macaque CD4 receptor. The infectivity of these viruses is ca. 20-
      to 50-fold lower with the rhesus and pig-tailed macaque versus the human CD4
      receptor. In contrast, culture-derived HIV-1 envelope variants that facilitate
      efficient replication in macaques showed similar infectivity with macaque and
      human CD4 receptors (within ~2-fold). The ability of an envelope to mediate entry
      using macaque CD4 correlated with its ability to mediate entry of cells
      expressing low levels of the human CD4 receptor and with soluble CD4 sensitivity.
      Species-specific differences in the functional capacity of the CD4 receptor to
      mediate entry mapped to a single amino acid difference at position 39 that is
      under strong positive selection, suggesting that the evolution of CD4 may have
      been influenced by its function as a viral receptor. These results also suggest
      that N39 in human CD4 may be a critical residue for interaction of transmitted
      HIV-1 variants. These studies provide important insights into virus-host cell
      interactions that have hindered the development of relevant nonhuman primate
      models for HIV-1 infection and provide possible markers, such as sCD4
      sensitivity, to identify potential HIV-1 variants that could be exploited for
      development of better SHIV/macaque model systems.

PMID- 22973038
TI  - Long-term nonprogressor and elite controller patients who control viremia have a
      higher percentage of methylation in their HIV-1 proviral promoters than aviremic
      patients receiving highly active antiretroviral therapy.
AB  - Several factors are involved in the control of HIV transcription/replication,
      including epigenetic modifications at the promoter level. Analysis of the HIV
      long terminal repeat (LTR) methylation status in infected patients controlling
      viremia is scarce. Herein, we show a higher degree of DNA methylation in the 5'
      LTR of long-term nonprogressor and elite controller (LTNP/EC) versus progressor
      patients and a positive correlation with time of infection, indicating a certain
      contribution of HIV LTR silencing in reducing the number of replicating viruses
      which may account for a delayed progression.

PMID- 22973037
TI  - Incorporation of host complement regulatory proteins into Newcastle disease virus
      enhances complement evasion.
AB  - Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor
      selective and is currently being considered as a clinical oncolytic virus and
      vaccine vector. In this study, we analyzed the effect of complement on the
      neutralization of NDV purified from embryonated chicken eggs, a common source for
      virus production. Fresh normal human serum (NHS) neutralized NDV by multiple
      pathways of complement activation, independent of neutralizing antibodies.
      Neutralization was associated with C3 deposition and the activation of C2, C3,
      C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was
      resistant to complement neutralization by NHS. To confirm whether the
      incorporation of regulators of complement activity (RCA) into the viral envelope
      afforded complement resistance, we grew NDV in CHO cells stably transfected with
      CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA
      expressing cells was resistant to complement by incorporating CD46 and CD55 on
      virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous
      restriction, since chicken sera devoid of neutralizing antibodies to NDV were
      able to effectively neutralize these virions. The incorporation of chicken RCA
      into NDV produced in embryonated eggs similarly provided species specificity
      toward chicken sera.

PMID- 22973039
TI  - Essential cell-autonomous role for interferon (IFN) regulatory factor 1 in IFN
      gamma-mediated inhibition of norovirus replication in macrophages.
AB  - Noroviruses (NVs) cause the majority of cases of epidemic nonbacterial
      gastroenteritis worldwide and contribute to endemic enteric disease. However, the
      molecular mechanisms responsible for immune control of their replication are not
      completely understood. Here we report that the transcription factor interferon
      regulatory factor 1 (IRF-1) is required for control of murine NV (MNV)
      replication and pathogenesis in vivo. This led us to studies documenting a cell
      autonomous role for IRF-1 in gamma interferon (IFN-gamma)-mediated inhibition of
      MNV replication in primary macrophages. This role of IRF-1 in the inhibition of
      MNV replication by IFN-gamma is independent of IFN-alphabeta signaling. While the
      signal transducer and activator of transcription STAT-1 was also required for IFN
      gamma-mediated inhibition of MNV replication in vitro, class II transactivator
      (CIITA), interferon regulatory factor 3 (IRF-3), and interferon regulatory factor
      7 (IRF-7) were not required. We therefore hypothesized that there must be a
      subset of IFN-stimulated genes (ISGs) regulated by IFN-gamma in a manner
      dependent only on STAT-1 and IRF-1. Analysis of transcriptional profiles of
      macrophages lacking various transcription factors confirmed this hypothesis.
      These studies identify a key role for IRF-1 in IFN-gamma-dependent control of
      norovirus infection in mice and macrophages.

PMID- 22973040
TI  - The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the
      nucleus.
AB  - Sterile alpha motif domain- and HD domain-containing protein 1 (SAMHD1) is a
      deoxynucleoside triphosphohydrolase that restricts the replication of
      lentiviruses in myeloid cells by hydrolyzing the cellular deoxynucleotide
      triphosphates to a level below that which is required for reverse transcription.
      Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency
      viruses (SIVs) encode the accessory protein viral protein X (Vpx) that
      counteracts SAMHD1. Vpx recruits SAMHD1 to a cullin4A-RING E3 ubiquitin ligase
      (CRL4), which targets the enzyme for proteasomal degradation. Vpx and SAMHD1 both
      localize to the nucleus of the cell. We identified the nuclear localization
      sequence (NLS) of SAMHD1 as a conserved KRPR sequence at amino acid residues 11
      to 14. SAMHD1 lacking a functional NLS localized to the cytoplasm but retained
      its triphosphohydrolase and antiviral activities. However, cytoplasmic SAMHD1 was
      resistant to Vpx-induced degradation, and its antiviral activity was not
      counteracted by Vpx. Cytoplasmic SAMHD1 interacted with Vpx and retained it in
      the cytoplasm. The inhibition of nuclear export with leptomycin B did not impair
      the ability of Vpx to degrade SAMHD1. These findings suggest that SAMHD1 is
      targeted by Vpx for ubiquitination and degradation in the nucleus.

PMID- 22973041
TI  - Impaired surfactant production by alveolar epithelial cells in a SCID-hu lung
      mouse model of congenital human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and life
      threatening lung-associated diseases in premature infants and immunocompromised
      children. Although the fetal lung is a major target organ of the virus, HCMV lung
      pathogenesis has remained unexplored, possibly as a result of extreme host range
      restriction. To overcome this hurdle, we generated a SCID-hu lung mouse model
      that closely recapitulates the discrete stages of human lung development in
      utero. Human fetal lung tissue was implanted into severe combined immunodeficient
      (CB17-scid) mice and inoculated by direct injection with the VR1814 clinical
      isolate of HCMV. Virus replication in the fetal lung was assessed by the
      quantification of infectious virus titers and HCMV genome copies and the
      detection of HCMV proteins by immunohistochemistry and Western blotting. We show
      that HCMV efficiently replicated in the lung implants during a 2-week period,
      forming large viral lesions. The virus productively infected alveolar epithelial
      and mesenchymal cells, imitating congenital infection of the fetal lung. HCMV
      replication triggered apoptosis near and within the viral lesions and impaired
      the production of surfactant proteins in the alveolar epithelium. Our findings
      highlight that congenital and neonatal HCMV infection can adversely impact lung
      development, leading to pneumonia and acute lung injury. We have successfully
      developed a small-animal model that closely recapitulates fetal and neonatal lung
      development and provides a valuable, biologically relevant tool for an
      understanding of the lung pathogenesis of HCMV as well as other human respiratory
      viruses. Additionally, this model would greatly facilitate the development and
      testing of new antiviral therapies for HCMV along with select human pulmonary
      pathogens.

PMID- 22973042
TI  - Global secretome characterization of herpes simplex virus 1-infected human
      primary macrophages.
AB  - Herpes simplex virus 1 (HSV-1) is a common pathogen infecting the majority of
      people worldwide at some stage in their lives. The early host response to viral
      infection is initiated by the cells of the innate immune response, including
      macrophages. Here, we have characterized the secretome of HSV-1-infected human
      primary macrophages using high-throughput quantitative proteomics. We identified
      and quantified 516 distinct human proteins with high confidence from the
      macrophage secretome upon HSV-1 infection, and the secretion of 411 proteins was
      >2-fold increased upon beta interferon (IFN-beta) priming and/or HSV-1 infection.
      Bioinformatics analysis of the secretome data revealed that most of the secreted
      proteins were intracellular, and almost 80% of the proteins whose secretion
      increased more than 2-fold were known exosomal proteins. This strongly suggests
      that nonclassical, vesicle-mediated protein secretion is activated in IFN-beta
      primed and HSV-1-infected macrophages. Proteins related to immune and
      inflammatory responses, interferon-induced proteins, and endogenous danger signal
      proteins were efficiently secreted upon IFN-beta priming and HSV-1 infection. The
      secreted IFN-induced proteins include interferon-induced tetratricopeptide
      protein 2 (IFIT2), IFIT3, signal transducer and activator of transcription 1
      (STAT1), and myxovirus resistance protein A (MxA), implicating that these
      proteins also have important extracellular antiviral functions. Proinflammatory
      cytokine interleukin-1beta was not released by HSV-1-infected macrophages,
      demonstrating that HSV-1 can antagonize inflammasome function. In conclusion, our
      results provide a global view of the secretome of HSV-1-infected macrophages,
      revealing host factors possibly having a role in antiviral defense.

PMID- 22973043
TI  - Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major
      histocompatibility complex class I expression in cells from human and macaque
      hosts.
AB  - B virus of the family Herpesviridae is endemic to rhesus macaques but results in
      80% fatality in untreated humans who are zoonotically infected. Downregulation of
      major histocompatibility complex (MHC) class I in order to evade CD8(+) T-cell
      activation is characteristic of most herpesviruses. Here we examined the cell
      surface presence and total protein expression of MHC class I molecules in B virus
      infected human foreskin fibroblast cells and macaque kidney epithelial cells in
      culture, which are representative of foreign and natural host initial target
      cells of B virus. Our results show <20% downregulation of surface MHC class I
      molecules in either type of host cells infected with B virus, which is
      statistically insignificantly different from that observed in uninfected cells.
      We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA
      G, involved in NK cell inhibition. Our results showed significant upregulation of
      HLA-E and HLA-G in host cells infected with B virus relative to the amounts
      observed in other herpesvirus-infected cells. These results suggest that B virus
      infected cell surfaces maintain normal levels of MHC class Ia molecules, a
      finding unique among simplex viruses. This is a unique divergence in immune
      evasion for B virus, which, unlike human simplex viruses, does not inhibit the
      transport of peptides for loading onto MHC class Ia molecules because B virus
      ICP47 lacks a transporter-associated protein binding domain. The fact that MHC
      class Ib molecules were significantly upregulated has additional implications for
      host-pathogen interactions.

PMID- 22973044
TI  - An interaction between human papillomavirus 16 E2 and TopBP1 is required for
      optimum viral DNA replication and episomal genome establishment.
AB  - In human papillomavirus DNA replication, the viral protein E2 forms homodimers
      and binds to 12-bp palindromic DNA sequences surrounding the origin of DNA
      replication. Via a protein-protein interaction, it then recruits the viral
      helicase E1 to an A/T-rich origin of replication, whereupon a dihexamer forms,
      resulting in DNA replication initiation. In order to carry out DNA replication,
      the viral proteins must interact with host factors that are currently not all
      known. An attractive cellular candidate for regulating viral replication is
      TopBP1, a known interactor of the E2 protein. In mammalian DNA replication,
      TopBP1 loads DNA polymerases onto the replicative helicase after the G(1)-to-S
      transition, and this process is tightly cell cycle controlled. The direct
      interaction between E2 and TopBP1 would allow E2 to bypass this cell cycle
      control, resulting in DNA replication more than once per cell cycle, which is a
      requirement for the viral life cycle. We report here the generation of an HPV16
      E2 mutant compromised in TopBP1 interaction in vivo and demonstrate that this
      mutant retains transcriptional activation and repression functions but has
      suboptimal DNA replication potential. Introduction of this mutant into a viral
      life cycle model results in the failure to establish viral episomes. The results
      present a potential new antiviral target, the E2-TopBP1 interaction, and increase
      our understanding of the viral life cycle, suggesting that the E2-TopBP1
      interaction is essential.

PMID- 22973045
TI  - Double-stranded RNA induces biphasic STAT1 phosphorylation by both type I
      interferon (IFN)-dependent and type I IFN-independent pathways.
AB  - Upon viral infection, pattern recognition receptors sense viral nucleic acids,
      leading to the production of type I interferons (IFNs), which initiate antiviral
      activities. Type I IFNs bind to their cognate receptor, IFNAR, resulting in the
      activation of signal-transducing activators of transcription 1 (STAT1). Thus, it
      has long been thought that double-stranded RNA (dsRNA)-induced STAT1
      phosphorylation is mediated by the transactivation of type I IFN signaling.
      Foreign RNA, such as viral RNA, in cells is sensed by the cytoplasmic sensors
      retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated
      gene 5 (MDA-5). In this study, we explored the molecular mechanism responsible
      for STAT1 phosphorylation in response to the sensing of dsRNA by cytosolic RNA
      sensors. Polyinosinic-poly(C) [poly(I:C)], a synthetic dsRNA that is sensed by
      both RIG-I and MDA-5, induces STAT1 phosphorylation. We found that the poly(I:C)
      induced initial phosphorylation of STAT1 is dependent on the RIG-I pathway and
      that MDA-5 is not involved in STAT1 phosphorylation. Furthermore, pretreatment of
      the cells with neutralizing antibody targeting the IFN receptor suppressed the
      initial STAT1 phosphorylation in response to poly(I:C), suggesting that this
      initial phosphorylation event is predominantly type I IFN dependent. In contrast,
      neither the known RIG-I pathway nor type I IFN is involved in the late
      phosphorylation of STAT1. In addition, poly(I:C) stimulated STAT1 phosphorylation
      in type I IFN receptor-deficient U5A cells with delayed kinetics. Collectively,
      our study provides evidence of a comprehensive regulatory mechanism in which
      dsRNA induces STAT1 phosphorylation, indicating the importance of STAT1 in
      maintaining very tight regulation of the innate immune system.

PMID- 22973046
TI  - Structure of hepatitis C virus envelope glycoprotein E2 antigenic site 412 to 423
      in complex with antibody AP33.
AB  - We have determined the crystal structure of the broadly neutralizing antibody
      (bnAb) AP33, bound to a peptide corresponding to hepatitis C virus (HCV) E2
      envelope glycoprotein antigenic site 412 to 423. Comparison with bnAb HCV1 bound
      to the same epitope reveals a different angle of approach to the antigen by bnAb
      AP33 and slight variation in its beta-hairpin conformation of the epitope. These
      structures establish two different modes of binding to E2 that antibodies adopt
      to neutralize diverse HCV.

PMID- 22973047
TI  - CTCF occupation of the herpes simplex virus 1 genome is disrupted at early times
      postreactivation in a transcription-dependent manner.
AB  - In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during
      latency have been previously identified. We hypothesized that CTCF binding to
      CTCF clusters in HSV-1 would be disrupted in a reactivation event. To
      investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed
      following sodium butyrate (NaB)- and explant-induced reactivation in the mouse.
      Our data show that the CTCF domains positioned within the HSV-1 genome,
      specifically around the latency-associated transcript (LAT) and ICP0 and ICP4
      regions of the genome, lose CTCF occupancy following the application of
      reactivation stimuli in wild-type virus. We also found that CTCF binding clusters
      upstream of the ICP0 and ICP4 promoters both function as classical insulators
      capable of acting as enhancer blockers of the LAT enhancer. Finally, our results
      suggest that CTCF occupation of domains in HSV-1 may be differentially regulated
      both during latency and at early times following reactivation by the presence of
      lytic transcripts and further implicate epigenetic regulation of HSV-1 as a
      critical component of the latency-reactivation transition.

PMID- 22973049
TI  - The different ligand-binding modes of relaxin family peptide receptors RXFP1 and
      RXFP2.
AB  - Relaxin and insulin-like peptide 3 (INSL3) are peptide hormones with a number of
      important physiological roles in reproduction, regulation of extracellular matrix
      turnover, and cardiovascular function. Relaxin and INSL3 mediate their actions
      through the closely related G-protein coupled receptors, relaxin family peptide
      receptors 1 and 2 (RXFP1 and RXFP2), respectively. These receptors have large
      extracellular domains (ECD) that contain high-affinity ligand-binding sites
      within their 10 leucine-rich repeat (LRR)-containing modules. Although relaxin
      can bind and activate both RXFP1 and RXFP2, INSL3 can only bind and activate
      RXFP2. To investigate whether this difference is related to the nature of the
      high-affinity ECD binding site or to differences in secondary binding sites
      involving the receptor transmembrane (TM) domain, we created a suite of
      constructs with RXFP1/2 chimeric ECD attached to single TM helices. We show that
      by changing as little as one LRR, representing four amino acid substitutions, we
      were able to engineer a high-affinity INSL3-binding site into the ECD of RXFP1.
      Molecular modeling of the INSL3-RXFP2 interaction based on extensive experimental
      data highlights the differences in the binding mechanisms of relaxin and INSL3 to
      the ECD of their cognate receptors. Interestingly, when the engineered RXFP1/2
      ECD were introduced into full-length RXFP1 constructs, INSL3 exhibited only low
      affinity and efficacy on these receptors. These results highlight critical
      differences both in the ECD binding and in the coordination of the ECD-binding
      site with the TM domain, and provide new mechanistic insights into the binding
      and activation events of RXFP1 and RXFP2 by their native hormone ligands.

PMID- 22973048
TI  - Constraints on viral evolution during chronic hepatitis C virus infection arising
      from a common-source exposure.
AB  - Extraordinary viral sequence diversity and rapid viral genetic evolution are
      hallmarks of hepatitis C virus (HCV) infection. Viral sequence evolution has
      previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) and
      neutralizing antibody responses in acute HCV infection. HCV evolution continues
      during chronic infection, but the pressures driving these changes are poorly
      defined. We analyzed plasma virus sequence evolution in 5.2-kb hemigenomes from
      multiple longitudinal time points isolated from individuals in the Irish anti-D
      cohort, who were infected with HCV from a common source in 1977 to 1978. We found
      phylogenetically distinct quasispecies populations at different plasma time
      points isolated late in chronic infection, suggesting ongoing viral evolution and
      quasispecies replacement over time. We saw evidence of early pressure driving net
      evolution away from a computationally reconstructed common ancestor, known as
      Bole1b, in predicted CTL epitopes and E1E2, with balanced evolution toward and
      away from the Bole1b amino acid sequence in the remainder of the genome. Late in
      chronic infection, the rate of evolution toward the Bole1b sequence increased,
      resulting in net neutral evolution relative to Bole1b across the entire 5.2-kb
      hemigenome. Surprisingly, even late in chronic infection, net amino acid
      evolution away from the infecting inoculum sequence still could be observed.
      These data suggest that, late in chronic infection, ongoing HCV evolution is not
      random genetic drift but rather the product of strong pressure toward a common
      ancestor and concurrent net ongoing evolution away from the inoculum virus
      sequence, likely balancing replicative fitness and ongoing immune escape.

PMID- 22973050
TI  - Identification of a dynamic mitochondrial protein complex driving cholesterol
      import, trafficking, and metabolism to steroid hormones.
AB  - Steroid hormones are critical for organismal development and health. The rate
      limiting step in steroidogenesis is the transport of cholesterol from the outer
      mitochondrial membrane (OMM) to the cytochrome P450 enzyme CYP11A1 in the inner
      mitochondrial membrane (IMM). Cholesterol transfer occurs through a complex
      termed the "transduceosome," in which cytosolic steroidogenic acute regulatory
      protein interacts with OMM proteins translocator protein and voltage-dependent
      anion channel (VDAC) to assist with the transfer of cholesterol to OMM. It has
      been proposed that cholesterol transfer from OMM to IMM occurs at specialized
      contact sites bridging the two membranes composed of VDAC and IMM adenine
      nucleotide translocase (ANT). Blue native PAGE of Leydig cell mitochondria
      identified two protein complexes that were able to bind cholesterol at 66- and
      800-kDa. Immunoblot and mass spectrometry analyses revealed that the 800-kDa
      complex contained the OMM translocator protein (18-kDa) and VDAC along with IMM
      CYP11A1, ATPase family AAA domain-containing protein 3A (ATAD3A), and optic
      atrophy type 1 proteins, but not ANT. Knockdown of ATAD3A, but not ANT or optic
      atrophy type 1, in Leydig cells resulted in a significant decrease in hormone
      induced, but not 22R-hydroxycholesterol-supported, steroid production. Using a 22
      phenoxazonoxy-5-cholene-3-beta-ol CYP11A1-specific probe, we further demonstrated
      that the 800-kDa complex offers the microenvironment needed for CYP11A1 activity.
      Addition of steroidogenic acute regulatory protein to the complex mobilized the
      cholesterol bound at the 800-kDa complex, leading to increased steroid formation.
      These results identify a bioactive, multimeric protein complex spanning the OMM
      and IMM unit that is responsible for the hormone-induced import, segregation,
      targeting, and metabolism of cholesterol.

PMID- 22973051
TI  - The microRNA (miR)-199a/214 cluster mediates opposing effects of progesterone and
      estrogen on uterine contractility during pregnancy and labor.
AB  - Progesterone (P(4)) and estradiol-17beta (E(2)) play critical and opposing roles
      in regulating myometrial quiescence and contractility during pregnancy and labor.
      Although these contrasting hormonal effects are likely mediated via differential
      regulation of inflammatory and contractile genes, the underlying mechanisms
      remain incompletely understood. Recently we discovered that targets of the
      microRNA (miR)-200 family, transcription factors zinc finger E-box binding
      homeobox (ZEB)-1 and ZEB2, serve as P(4)/progesterone receptor-mediated
      regulators of uterine quiescence during pregnancy. In the present study, we found
      that levels of the clustered miRNAs, miR-199a-3p and miR-214, were significantly
      decreased in laboring myometrium of pregnant mice and humans and in an
      inflammatory mouse model of preterm labor, whereas the miR-199a-3p/miR-214
      target, cyclooxygenase-2, a critical enzyme in synthesis of proinflammatory
      prostaglandins, was coordinately increased. Overexpression of miR-199a-3p and miR
      214 in cultured human myometrial cells inhibited cyclooxygenase-2 protein and
      blocked TNF-alpha-induced myometrial cell contractility, suggesting their
      physiological relevance. Notably, E(2) treatment of ovariectomized mice
      suppressed, whereas P(4) enhanced uterine miR-199a-3p/214 expression.
      Intriguingly, these opposing hormonal effects were mediated by ZEB1, which is
      induced by P(4), inhibited by E(2) and activates miR199a/214 transcription.
      Together, these findings identify miR-199a-3p/miR-214 as important regulators of
      myometrial contractility and provide new insight into strategies to prevent
      preterm birth.

PMID- 22973052
TI  - Human RECQL5 participates in the removal of endogenous DNA damage.
AB  - Human RECQL5 is a member of the RecQ helicase family, which maintains genome
      stability via participation in many DNA metabolic processes, including DNA
      repair. Human cells lacking RECQL5 display chromosomal instability. We find that
      cells depleted of RECQL5 are sensitive to oxidative stress, accumulate endogenous
      DNA damage, and increase the cellular poly(ADP-ribosyl)ate response. In contrast
      to the RECQ helicase family members WRN, BLM, and RECQL4, RECQL5 accumulates at
      laser-induced single-strand breaks in normal human cells. RECQL5 depletion
      affects the levels of PARP-1 and XRCC1, and our collective results suggest that
      RECQL5 modulates and/or directly participates in base excision repair of
      endogenous DNA damage, thereby promoting chromosome stability in normal human
      cells.

PMID- 22973053
TI  - SLAC, a complex between Sla1 and Las17, regulates actin polymerization during
      clathrin-mediated endocytosis.
AB  - During clathrin-mediated endocytosis, branched actin polymerization nucleated by
      the Arp2/3 complex provides force needed to drive vesicle internalization. Las17
      (yeast WASp) is the strongest activator of the Arp2/3 complex in yeast cells; it
      is not autoinhibited and arrives to endocytic sites 20 s before actin
      polymerization begins. It is unclear how Las17 is kept inactive for 20 s at
      endocytic sites, thus restricting actin polymerization to late stages of
      endocytosis. In this paper, we demonstrate that Las17 is part of a large and
      biochemically stable complex with Sla1, a clathrin adaptor that inhibits Las17
      activity. The interaction is direct, multivalent, and strong, and was mapped to
      novel Las17 polyproline motifs that are simultaneously class I and class II. In
      vitro pyrene-actin polymerization assays established that Sla1 inhibition of
      Las17 activity depends on the class I/II Las17 polyproline motifs and is based on
      competition between Sla1 and monomeric actin for binding to Las17. Furthermore,
      live-cell imaging showed the interaction with Sla1 is important for normal Las17
      recruitment to endocytic sites, inhibition during the initial 20 s, and efficient
      endocytosis. These results advance our understanding of the regulation of actin
      polymerization in endocytosis.

PMID- 22973054
TI  - Proinflammatory cytokine secretion is suppressed by TMEM16A or CFTR channel
      activity in human cystic fibrosis bronchial epithelia.
AB  - Cystic fibrosis (CF) is caused by the functional expression defect of the CF
      transmembrane conductance regulator (CFTR) chloride channel at the apical plasma
      membrane. Impaired bacterial clearance and hyperactive innate immune response are
      hallmarks of the CF lung disease, yet the existence of and mechanism accounting
      for the innate immune defect that occurs before infection remain controversial.
      Inducible expression of either CFTR or the calcium-activated chloride channel
      TMEM16A attenuated the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and
      CXCL1/2 in two human respiratory epithelial models under air-liquid but not
      liquid-liquid interface culture. Expression of wild-type but not the inactive
      G551D-CFTR indicates that secretion of the chemoattractant IL-8 is inversely
      proportional to CFTR channel activity in cftr(?F508/?F508) immortalized and
      primary human bronchial epithelia. Similarly, direct but not P2Y receptor
      mediated activation of TMEM16A attenuates IL-8 secretion in respiratory
      epithelia. Thus augmented proinflammatory cytokine secretion caused by defective
      anion transport at the apical membrane may contribute to the excessive and
      persistent lung inflammation in CF and perhaps in other respiratory diseases
      associated with documented down-regulation of CFTR (e.g., chronic obstructive
      pulmonary disease). Direct pharmacological activation of TMEM16A offers a
      potential therapeutic strategy to reduce the inflammation of CF airway epithelia.

PMID- 22973055
TI  - Sub1 associates with Spt5 and influences RNA polymerase II transcription
      elongation rate.
AB  - The transcriptional coactivator Sub1 has been implicated in several steps of mRNA
      metabolism in yeast, such as the activation of transcription, termination, and 3'
      end formation. In addition, Sub1 globally regulates RNA polymerase II
      phosphorylation, and most recently it has been shown that it is a functional
      component of the preinitiation complex. Here we present evidence that Sub1 plays
      a significant role in transcription elongation by RNA polymerase II (RNAPII). We
      show that SUB1 genetically interacts with the gene encoding the elongation factor
      Spt5, that Sub1 influences Spt5 phosphorylation of the carboxy-terminal domain of
      RNAPII largest subunit by the kinase Bur1, and that both Sub1 and Spt5 copurify
      in the same complex, likely during early transcription elongation. Indeed, our
      data indicate that Sub1 influences Spt5-Rpb1 interaction. In addition,
      biochemical and molecular data show that Sub1 influences transcription elongation
      of constitutive and inducible genes and associates with coding regions in a
      transcription-dependent manner. Taken together, our results indicate that Sub1
      associates with Spt5 and influences Spt5-Rpb1 complex levels and consequently
      transcription elongation rate.

PMID- 22973056
TI  - Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral
      cancer.
AB  - Activation of the cellular DNA damage response (DDR) is an important determinant
      of cell sensitivity to cisplatin and other chemotherapeutic drugs that eliminate
      tumor cells through induction of DNA damage. It is therefore important to
      investigate whether alterations of the DNA damage-signaling pathway confer
      chemoresistance in cancer cells and whether pharmacologic manipulation of the DDR
      pathway can resensitize these cells to cancer therapy. In a panel of
      oral/laryngeal squamous cell carcinoma (SCC) cell lines, we observed deficiencies
      in DNA damage signaling in correlation with cisplatin resistance, but not with
      DNA repair. These deficiencies are consistent with reduced expression of
      components of the ataxia telangiectasia mutated (ATM)-dependent signaling pathway
      and, in particular, strong upregulation of Wip1, a negative regulator of the ATM
      pathway. Wip1 knockdown or inhibition enhanced DNA damage signaling and
      resensitized oral SCC cells to cisplatin. In contrast to the previously reported
      involvement of Wip1 in cancer, Wip1 upregulation and function in these SCC cells
      is independent of p53. Finally, using xenograft tumor models, we showed that Wip1
      upregulation promotes tumorigenesis and its inhibition improves the tumor
      response to cisplatin. Thus, this study reveals that chemoresistance in oral SCCs
      is partially attributed to deficiencies in DNA damage signaling, and Wip1 is an
      effective drug target for enhanced cancer therapy.

PMID- 22973057
TI  - Epithelial-mesenchymal transition and stem cell markers in patients with HER2
      positive metastatic breast cancer.
AB  - Currently, there is extensive information about circulating tumor cells (CTC) and
      their prognostic value; however, little is known about other characteristics of
      these cells. In this prospective study, we assessed the gene transcripts of
      epithelial-to-mesenchymal transition-inducing transcription factors (EMT-TF) and
      cancer stem cell (CSC) features in patients with HER2(+) metastatic breast cancer
      (MBC). Epithelial cells were enriched from peripheral blood mononuclear cells
      (PBMC) using antibody-coated anti-CD326 antibody (CD326(+)) magnetic beads, and
      the residual CD326(-) PBMCs were further depleted of leukocytes using anti-CD45
      antibody-coated magnetic beads (CD326(-)CD45(-)). RNA was extracted from all cell
      fractions, reverse transcribed to cDNA, and subjected to quantitative reverse
      transcription PCR to detect EMT-TFs (TWIST1, SNAIL1, ZEB1, and TG2) as a measure
      of CTCs undergoing EMT (EMT-CTCs). In addition, PBMCs were analyzed using
      multiparameter flow cytometry for ALDH activity and CSCs that express CD24, CD44,
      and CD133. Twenty-eight patients were included in this study. At least one EMT-TF
      mRNA was elevated in the CTCs of 88.2% of patients and in the CD326(-)CD45(-)
      cell fraction of 60.7% of patients. The CD326(-)CD45(-) fraction of patients with
      elevated SNAIL1 and ZEB1 transcripts also had a higher percentage of
      ALDH(+)/CD133(+) cells in their blood than did patients with normal SNAIL1 and
      ZEB1 expression (P = 0.038). Our data indicate that patients with HER2(+) MBCs
      have EMT-CTCs. Moreover, an enrichment of CSCs was found in CD326(-)CD45(-)
      cells. Additional studies are needed to determine whether EMT-CTCs and CSCs have
      prognostic value in patients with HER2(+) MBCs treated with trastuzumab-based
      therapy.

PMID- 22973059
TI  - Cd2+ block and permeation of CaV3.1 (alpha1G) T-type calcium channels: candidate
      mechanism for Cd2+ influx.
AB  - Cd2+ is an industrial pollutant that can cause cytotoxicity in multiple organs.
      We examined the effects of extracellular Cd2+ on permeation and gating of
      Ca(v)3.1 (alpha1G) channels stably transfected in HEK293 cells, by using whole
      cell recording. With the use of instantaneous I-V currents (measured after strong
      depolarization) to isolate the effects on permeation, Cd2+ rapidly blocked
      currents with 2 mM Ca2+ in a voltage-dependent manner. The block caused by Cd2+
      was relieved at more-hyperpolarized potentials, which suggests that Cd2+ can
      permeate through the selectivity filter of the channel into the cytosol. In the
      absence of other permeant ions (Ca2+ and Na+ replaced by N-methyl-d-glucamine),
      Cd2+ carried sizable inward currents through Ca(v)3.1 channels (210 +/- 20 pA at 
      60 mV with 2 mM Cd2+). Ca(v)3.1 channels have a significant "window current" at
      that voltage (open probability, ~1%), which makes them a candidate pathway for
      Cd2+ entry into cells during Cd2+ exposure. Incubation with radiolabeled 109Cd2+
      confirmed uptake of Cd2+ into cells with Ca(v)3.1 channels.

PMID- 22973058
TI  - 8-Amino-adenosine activates p53-independent cell death of metastatic breast
      cancers.
AB  - 8-Amino-adenosine (8-NH(2)-Ado) is a ribose sugar nucleoside analogue that
      reduces cellular ATP levels and inhibits mRNA synthesis. Estrogen receptor
      negative (ER-) metastatic breast cancers often contain mutant p53; therefore, we
      asked if 8-NH(2)-Ado could kill breast cancer cells without activating the p53
      pathway. Regardless of the breast cancer subtype tested or the p53 status of the
      cells, 8-NH(2)-Ado was more cytotoxic than either gemcitabine or etoposide. 8
      NH(2)-Ado treatment inhibited cell proliferation, activated cell death, and did
      not activate transcription of the p53 target gene p21 or increase protein levels
      of either p53 or p21. This occurred in the estrogen receptor-positive (ER+) MCF-7
      cells that express wild-type p53, the ER+ T47-D cells that express mutant p53,
      and the ER- MDA-MB-468 cells or MDA-MB-231 cells that both express mutant p53. 8
      NH(2)-Ado induced apoptotic death of MCF-7 cells and apoptosis was not inhibited
      by knockdown of functional p53. Moreover, the pan-caspase inhibitor Z-VAD blocked
      the 8-NH(2)-Ado-induced MCF-7 cell death. Interestingly, 8-NH(2)-Ado caused the
      MDA-MB-231 cells to detach from the plate with only limited evidence of apoptotic
      cell death markers and the cell death was not inhibited by Z-VAD. Inhibition of
      MDA-MB-231 cell autophagy, by reduction of ATG7 or 3-methyladenine treatment, did
      not block this 8-NH(2)-Ado-mediated cytotoxicity. Importantly 8-NH(2)-Ado was
      highly cytotoxic to triple-negative breast cancer cells and worked through a
      pathway that did not require wild-type p53 for cytoxicity. Therefore, 8-NH(2)-Ado
      should be considered for the treatment of triple-negative breast cancers that are
      chemotherapy resistant.

PMID- 22973061
TI  - Analysis of multiple histamine H4 receptor compound classes uncovers Galphai
      protein- and beta-arrestin2-biased ligands.
AB  - After the recent description of beta-arrestin2 recruitment to the human histamine
      H4 receptor (hH4R) in response to the well known H4R antagonist 1-[(5-chloro-1H
      indol-2-yl)carbonyl]-4-methyl-piperazine (JNJ 7777120), we evaluated in this
      study the efficacy of 31 known hH4R ligands to induce Galpha(i) protein signaling
      and beta-arrestin2 recruitment by the hH4R. The selected hH(4)R ligands belong to
      nine different structural classes that partly cover (pre)clinical trial
      candidates. We have identified hH4R ligands with a significant bias for the
      Galpha(i) protein or beta-arrestin2 pathway on the basis of efficacy differences.
      In addition, hH4R antagonists that did not show positive efficacy in either
      functional readouts were found. A common trend in pathway preference for the nine
      different ligand classes could not be observed. In particular, the isothiourea
      class shows very diverse results, varying from Galpha(i) protein-biased or beta
      arrestin2-biased to nonbiased antagonists upon minor structural changes. The
      identified biased hH4R ligands are important pharmacological tools to unravel the
      significance of biased hH4R signaling in H4R pharmacology.

PMID- 22973060
TI  - Fe2+ block and permeation of CaV3.1 (alpha1G) T-type calcium channels: candidate
      mechanism for non-transferrin-mediated Fe2+ influx.
AB  - Iron is a biologically essential metal, but excess iron can cause damage to the
      cardiovascular and nervous systems. We examined the effects of extracellular Fe2+
      on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells,
      by using whole-cell recording. Precautions were taken to maintain iron in the
      Fe2+ state (e.g., use of extracellular ascorbate). With the use of instantaneous
      I-V currents (measured after strong depolarization) to isolate the effects on
      permeation, extracellular Fe2+ rapidly blocked currents with 2 mM extracellular
      Ca2+ in a voltage-dependent manner, as described by a Woodhull model with K(D) =
      2.5 mM at 0 mV and apparent electrical distance delta = 0.17. Extracellular Fe2+
      also shifted activation to more-depolarized voltages (by ~10 mV with 1.8 mM
      extracellular Fe2+) somewhat more strongly than did extracellular Ca2+ or Mg2+,
      which is consistent with a Gouy-Chapman-Stern model with surface charge density
      sigma = 1 e(-)/98 A2 and K(Fe) = 4.5 M-1 for extracellular Fe2+. In the absence
      of extracellular Ca2+ (and with extracellular Na+ replaced by TEA), Fe2+ carried
      detectable, whole-cell, inward currents at millimolar concentrations (73 +/- 7 pA
      at -60 mV with 10 mM extracellular Fe2+). With a two-site/three-barrier Eyring
      model for permeation of Ca(V)3.1 channels, we estimated a transport rate for Fe2+
      of ~20 ions/s for each open channel at -60 mV and pH 7.2, with 1 MUM
      extracellular Fe2+ (with 2 mM extracellular Ca2+). Because Ca(V)3.1 channels
      exhibit a significant "window current" at that voltage (open probability, ~1%),
      Ca(V)3.1 channels represent a likely pathway for Fe2+ entry into cells with
      clinically relevant concentrations of extracellular Fe2+.

PMID- 22973062
TI  - LC2 and OsVIL2 promote rice flowering by photoperoid-induced epigenetic silencing
      of OsLF.
AB  - Proper flowering time is essential for plant reproduction. Winter annual
      Arabidopsis thaliana needs vernalization before flowering, during which AtVILs
      (VIN3 and VRN5, components of PRC2 complex) mediate the H3K27 tri-methylation at
      the FLC locus (a floral repressor) to repress the FLC expression and hence to
      induce flowering. However, how VILs (VIL, VERNALIZATION INSENSITIVE 3-LIKE)
      function in rice is unknown. Here we demonstrated that rice LC2 (OsVIL3) and
      OsVIL2 (two OsVILs, possible components of PRC2 complex) promote rice flowering.
      Our results showed that expressions of LC2 and OsVIL2 are induced by SD (short
      day) conditions and both lc2 mutant and OsVIL2-RNAi lines display delayed heading
      date, consistent with the reduced expression levels of Hd1 and Hd3a.
      Interestingly, LC2 binds to the promoter region of a floral repressor OsLF and
      represses the OsLF expression via H3K27 tri-methylation modification. In
      addition, OsLF directly regulates the Hd1 expression through binding to Hd1
      promoter. These results first demonstrated that the putative PRC2 in rice is
      involved in photoperiod flowering regulation, which is different from that of
      Arabidopsis, and revealed that LC2 binds the promoter region of target gene,
      presenting a possible mechanism of the recruitment process of PRC2 complex to its
      target genes. The studies provide informative clues on the epigenetic control of
      rice flowering.

PMID- 22973063
TI  - Epigenetic suppression of T-DNA insertion mutants in Arabidopsis.
AB  - T-DNA insertion mutants have been widely used to define gene functions in
      Arabidopsis and in other plants. Here, we report an unexpected phenomenon of
      epigenetic suppression of T-DNA insertion mutants in Arabidopsis. When the two T
      DNA insertion mutants, yuc1-1 and ag-TD, were crossed together, the defects in
      all of the ag-TD plants in the F2 population were partially suppressed regardless
      of the presence of yuc1-1. Conversion of ag-TD to the suppressed ag-TD (named as
      ag-TD*) did not follow the laws of Mendelian genetics. The ag-TD* could be stably
      transmitted for many generations without reverting to ag-TD, and ag-TD* had the
      capacity to convert ag-TD to ag-TD*. We show that epigenetic suppression of T-DNA
      mutants is not a rare event, but certain structural features in the T-DNA mutants
      are needed in order for the suppression to take place. The suppressed T-DNA
      mutants we observed were all intronic T-DNA mutants and the T-DNA fragments in
      both the trigger T-DNA as well as in the suppressed T-DNA shared stretches of
      identical sequences. We demonstrate that the suppression of intronic T-DNA
      mutants is mediated by trans-interactions between two T-DNA insertions. This work
      shows that caution is needed when intronic T-DNA mutants are used.

PMID- 22973064
TI  - Phytochromes and phytohormones: the shrinking degree of separation.

PMID- 22973065
TI  - Recent insights into brassinosteroid signaling in plants: its dual control of
      plant immunity and stomatal development.
AB  - Brassinosteroid (BR) signaling, plant innate immunity, and stomatal developments
      are three pathways that are initiated by receptor-like kinases. This commentary
      focuses on the latest findings in the role of BR signaling in plant immunity and
      stomatal development that provide some insight into the molecular mechanism of
      the BR signal pathway interacting with other receptor signaling pathways.

PMID- 22973066
TI  - Estimating Size and Trend of the North Interlake Woodland Caribou Population
      Using Fecal-DNA and Capture-Recapture Models.
AB  - A critical step in recovery efforts for endangered and threatened species is the
      monitoring of population demographic parameters. As part of these efforts, we
      evaluated the use of fecal-DNA based capture-recapture methods to estimate
      population sizes and population rate of change for the North Interlake woodland
      caribou herd (Rangifer tarandus caribou), Manitoba, Canada. This herd is part of
      the boreal population of woodland caribou, listed as threatened under the federal
      Species at Risk Act (2003) and the provincial Manitoba Endangered Species Act
      (2006). Between 2004 and 2009 (9 surveys), we collected 1,080 fecal samples and
      identified 180 unique genotypes (102 females and 78 males). We used a robust
      design survey plan with 2 surveys in most years and analysed the data with
      Program MARK to estimate encounter rates (p), apparent survival rates (phi),
      rates of population change (lambda), and population sizes (N). We estimated these
      demographic parameters for males and females and for 2 genetic clusters within
      the North Interlake. The population size estimates were larger for the Lower than
      the Upper North Interlake area and the proportion of males was lower in the Lower
      (33%) than the Upper North Interlake (49%). Population rate of change for the
      entire North Interlake area (2005-2009) using the robust design Pradel model was
      significantly <1.0 (lambda = 0.90, 95% CI: 0.82-0.99) and varied between sex and
      area with the highest being for males in Lower North Interlake (lambda = 0.98,
      95% CI: 0.83-1.13) and the lowest being for females in Upper North Interlake
      (lambda = 0.83, 95% CI: 0.69-0.97). The additivity of lambda between sex and area
      is supported on the log scale and translates into males having a lambda that is
      0.09 greater than females and independent of sex, Lower North Interlake having a
      lambda that is 0.06 greater than Upper North Interlake. Population estimates
      paralleled these declining trends, which correspond to trends observed in other
      fragmented populations of woodland caribou along the southern part of their
      range. The results of this study clearly demonstrate the applicability and
      success of non-invasive genetic sampling in monitoring populations of woodland
      caribou. (c) 2012 The Wildlife Society.

PMID- 22973067
TI  - Synthesis and Thermomechanical Behavior of (Qua)ternary Thiol-ene(/acrylate)
      Copolymers.
AB  - The objective of this work is to characterize and understand the structure-to
      thermo-mechanical property relationship in thiol-ene and thiol-ene/acrylate
      copolymers in order to complement the existing studies on the kinetics of this
      polymerization reaction. Forty-one distinct three- and four-part mixtures were
      created with systematically varied functionality, chemical structure, type and
      concentration of crosslinker. The resulting polymers were subjected to dynamic
      mechanical analysis and tensile testing at their glass transition temperature,
      T(g), to quantify and understand their thermomechanical properties. The copolymer
      systems exhibited a broad range of T(g), rubbery modulus - E(r) and failure
      strain. The addition of a difunctional high-T(g) acrylate to several three-part
      systems increased the resultant T(g) and E(r). Higher crosslink densities
      generally resulted in higher stress and lower strain at failure. The tunability
      of the thermomechanical properties of these copolymer systems is discussed in
      terms of inherent advantages and limitations in light of pure acrylate systems.

PMID- 22973068
TI  - Microwave-assisted synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3
      (piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B-355252): a new potentiator of
      Nerve Growth Factor (NGF)-induced neurite outgrowth.
AB  - The synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1
      yl)phenoxy)thiophene-2-sulfonamide (B-355252) using a MW-assisted nucleophilic
      aromatic substitution (S(N)Ar) reaction will be discussed. Utilization of this
      method allowed for the rapid generation of B-355252 heteroaryl ether core
      structure in the presence of cesium carbonate in dimethylformamide or
      tripotassium phosphate in N-methyl-2-pyrrolidone in 94% yield. Evaluation of B
      355252 enhancement of nerve growth factor's ability to stimulate neurite
      outgrowths was determined using NS-1 cells.

PMID- 22973069
TI  - Order restricted inference for multivariate binary data with application to
      toxicology.
AB  - In many applications researchers collect multivariate binary response data under
      two or more, naturally ordered, experimental conditions. In such situations one
      is often interested in using all binary outcomes simultaneously to detect an
      ordering among the experimental conditions. To make such comparisons we develop a
      general methodology for testing for the multivariate stochastic order between K
      >= 2 multivariate binary distributions. The proposed test uses order restricted
      estimators which, according to our simulation study, are more efficient than the
      unrestricted estimators in terms of mean squared error. The power of the proposed
      test was compared with several alternative tests. These included procedures which
      combine individual univariate tests for order, such as union intersection tests
      and a Bonferroni based test. We also compared the proposed test with unrestricted
      Hotelling's T(2) type test. Our simulations suggest that the proposed method
      competes well with these alternatives. The gain in power is often substantial.
      The proposed methodology is illustrated by applying it to a two-year rodent
      cancer bioassay data obtained from the US National Toxicology Program (NTP).
      Supplemental materials are available online.

PMID- 22973070
TI  - Rationally designed mutations convert complexes of human recombinant T cell
      receptor ligands into monomers that retain biological activity.
AB  - Single-chain human recombinant T cell receptor ligands derived from the peptide
      binding/TCR recognition domain of human HLA-DR2b (DRA*0101/DRB1*1501) produced in
      Escherichia coli with and without amino-terminal extensions containing antigenic
      peptides have been described previously. While molecules with the native sequence
      retained biological activity, they formed higher order aggregates in solution. In
      this study, we used site-directed mutagenesis to modify the beta-sheet platform
      of the DR2-derived RTLs, obtaining two variants that were monomeric in solution
      by replacing hydrophobic residues with polar (serine) or charged (aspartic acid)
      residues. Size exclusion chromatography and dynamic light scattering demonstrated
      that the modified RTLs were monomeric in solution, and structural
      characterization using circular dichroism demonstrated the highly ordered
      secondary structure of the RTLs. Peptide binding to the 'empty' RTLs was
      quantified using biotinylated peptides, and functional studies showed that the
      modified RTLs containing covalently tethered peptides were able to inhibit
      antigen-specific T cell proliferation in vitro, as well as suppress experimental
      autoimmune encephalomyelitis in vivo. These studies demonstrated that RTLs
      encoding the Ag-binding/TCR recognition domain of MHC class II molecules are
      innately very robust structures, capable of retaining potent biological activity
      separate from the Ig-fold domains of the progenitor class II structure, with
      prevention of aggregation accomplished by modification of an exposed surface that
      was buried in the progenitor structure.

PMID- 22973071
TI  - Low persistence of a monocarpic invasive plant in historical sites biases our
      perception of its actual distribution.
AB  - AIM: As accurate and up-to-date distribution data for plant species are rarely
      available, cumulative records over long periods of time are frequently used for
      mapping distributions, without taking into account that species do not persist in
      their historical localities forever. However, persistence is highly relevant in
      changing modern landscapes, especially for invasive species that dynamically
      spread in unstable human-made habitats. We studied how an invasive species,
      Heracleum mantegazzianum, persists at sites once colonized and how its ability to
      persist affects its distribution.  LOCATION: The Czech Republic.  METHODS: We
      visited 521 localities of H. mantegazzianum occurrence reported in the literature
      and herbaria to determine whether the species still occurs at these sites. By
      using G-tests and classification trees, we explored the roles of various factors
      affecting its persistence at a site.  RESULTS: Of the total number of 521
      historical sites at which the species has occurred since the end of the 19th
      century, it persists at only 124 (23.8%). The persistence rate differs with
      respect to habitat type and is highest in meadows and forest margins. Analysis
      using classification trees indicated that the factors that best explain
      persistence are: type of habitat (with meadow and forest margins over
      represented); urbanity (with a higher persistence outside urban areas); proximity
      to the place of the species' introduction into the country; metapopulation
      connectivity; and distance to the nearest neighbouring population.  MAIN
      CONCLUSIONS: The use of cumulative historical records as a measure of species
      distribution, which is common in invasion literature, can seriously overestimate
      the actual distribution of alien plant species with low persistence. In the case
      of alien species such as H. mantegazzanium, which is non-clonal and reproduces
      only by seed, estimates of distribution and spread based on historical data are
      informative about potentially suitable habitat but may be unreliable as
      indicators of current occurrence and invasion dynamics.

PMID- 22973072
TI  - Proteomic analyses of the vitreous humour.
AB  - The human vitreous humour (VH) is a transparent, highly hydrated gel, which
      occupies the posterior segment of the eye between the lens and the retina.
      Physiological and pathological conditions of the retina are reflected in the
      protein composition of the VH, which can be sampled as part of routine surgical
      procedures. Historically, many studies have investigated levels of individual
      proteins in VH from healthy and diseased eyes. In the last decade, proteomics
      analyses have been performed to characterise the proteome of the human VH and
      explore networks of functionally related proteins, providing insight into the
      aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent
      proteomic studies on the VH from animal models of autoimmune uveitis have
      identified new signalling pathways associated to autoimmune triggers and
      intravitreal inflammation. This paper aims to guide biological scientists through
      the different proteomic techniques that have been used to analyse the VH and
      present future perspectives for the study of intravitreal inflammation using
      proteomic analyses.

PMID- 22973073
TI  - Role of inflammation in endophthalmitis.
AB  - Inflammation originating from infection of the vitreous cavity is called
      endophthalmitis. Attention has been focused on the epidemiologic, microbiologic
      reports, and treatment options; unfortunately, the role of the host immune
      reaction in the visual function damage is still not well understood.
      Endophthalmitis occurs most frequently after cataract surgery. In this paper we
      review the published literature regarding inflammatory mediators and apoptosis
      during the course of endophthalmitis. Toll-like receptors, cytokines, high
      mobility group box 1 proteins, aB-crystallin and apoptosis have been studied
      during clinical and experimental cases of endophthalmitis. Further understanding
      of the host-immune reaction to vitreous infection is essential for the
      development of new therapies. The use of intravitreal antibiotics and
      corticosteroids, vitrectomy and systemic antibiotics for the preservation of
      visual function is still discouraging.

PMID- 22973074
TI  - Value of C-reactive protein in predicting left ventricular remodelling in
      patients with a first ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: To assess the value of C-reactive protein (CRP) in predicting
      postinfarct left ventricular remodelling (LVR). METHODS: We measured in-hospital
      plasma CRP concentrations in patients with a first ST-segment elevation
      myocardial infarction (STEMI). RESULTS: LVR was present at 6 months in 27.8% of
      198 patients. CRP concentration rose during the first 24 h, mainly in LVR group.
      The prevalence of LVR was higher in patients from the highest quartile of CRP
      concentrations at 24 h as compared to those from any other quartile (odds ratio
      (OR) 3.48, 95% confidence interval (95% CI) 1.76-6.88). Multivariate analysis
      identified CRP concentration at 24 h (OR for a 10 mg/L increase 1.29, 95% CI 1.04
      1.60), B-type natriuretic peptide at discharge (OR for a 100 pg/mL increase 1.21,
      95% CI 1.05-1.39), body mass index (OR for a 1 kg/m(2) increase 1.10, 95% CI 1.01
      1.21), and left ventricular end-diastolic volume (OR for a 1 mL increase 0.98,
      95% CI 0.96-0.99) as independent predictors of LVR. The ROC analysis revealed a
      limited discriminative value of CRP (area under the curve 0.61; 95% CI 0.54-0.68)
      in terms of LVR prediction. CONCLUSIONS: Measurement of CRP concentration at 24 h
      after admission possesses a significant but modest value in predicting LVR after
      a first STEMI.

PMID- 22973076
TI  - Hilda Mary Woods MBE, DSc, LRAM, FSS (1892-1971): reflections on a Fellow of the
      Royal Statistical Society.
AB  - We have previously described the content of a text by Woods and Russell, An
      Introduction to Medical Statistics, compared it with Principles of Medical
      Statistics by Hill and set both volumes against the background of vital
      statistics up until 1937. The two books mark a watershed in the history of
      medical statistics. Very little has been recorded about the life and career of
      the first author of the earlier textbook, who was a Fellow of the Royal
      Statistical Society for at least 25 years, an omission which we can now rectify
      with this paper. We describe her education, entry into medical statistics,
      relationship with Major Greenwood and her subsequent career and life in Ceylon,
      Kenya, Australia, England and South Africa.

PMID- 22973075
TI  - Sterile endophthalmitis after intravitreal injections.
AB  - Sterile endophthalmitis appears as an infrequent complication of intravitreal
      injections and seems to develop mainly in the context of the off-label use of
      drugs that have not been conceived for intravitreous administration. The
      aetiology of sterile endophthalmitis, independently of the administered drug,
      remains uncertain and a multifactorial origin cannot be discarded. Sterile
      inflammation secondary both to intravitreal triamcinolone acetonide and to
      intravitreal bevacizumab share many characteristics such as the acute and
      painless vision loss present in the big majority of the cases. Dense vitreous
      opacity is a common factor, while anterior segment inflammation appears to be
      mild to moderate. In eyes with sterile endophthalmitis, visual acuity improves
      progressively as the intraocular inflammation reduces without any specific
      treatment. If by any chance the ophthalmologist is not convinced by the sterile
      origin of the inflammation, this complication must be treated as an acute
      endophthalmitis because of the devastating visual prognosis of this intraocular
      infection in the absence of therapy.

PMID- 22973077
TI  - Use of ubiquitous materials for the estimation of accidental exposures.

PMID- 22973078
TI  - Dosimetric analysis of trigeminal nerve, brain stem doses in CyberKnife
      radiosurgery of trigeminal neuralgia.
AB  - CyberKnife radiosurgery treatment of Trigeminal neuralgia (TN) is performed as a
      non-invasive image guided procedure. The prescription dose for TN is very high.
      The brainstem is the adjacent critical organ at risk (OAR) which is prone to
      receive the very high target dose of TN. The present study is to analyze the dose
      distribution inside the tiny trigeminal nerve target and also to analyze the dose
      fall off in the brain stem. Seven TN cases treated between November 2010 and
      January 2012 were taken for this study retrospectively. The treatment plans were
      analyzed for target dose conformity, homogeneity and dose coverage. In the
      brainstem the volume doses D(1%), D(2%) were taken for analyzing the higher doses
      in the brain stem. The dose fall off was analyzed in terms of D(5%) and D(10%).
      The mean value of maximum dose within the trigeminal nerve target was 73.5+/
      2.1Gy (P=0.0007) and the minimum dose was 50.0+/-4.1Gy (P=0.1315). The mean
      conformity index was 2.19 and the probable reason could be the smallest
      CyberKnife collimator of 5mm used in the treatment plan. The mean D(1%), of the
      brainstem was 10.5+/- 2.1Gy (P=0.5316) and the mean value of the maximum point
      dose within the brainstem was 35.6+/-3.8Gy. This shows the degree of dose fall
      off within the brainstem. Though the results of the present study are showing
      superior sparing of brain stem and reasonable of target coverage, it is necessary
      to execute the treatment plan with greater accuracy in CyberKnife as the
      immobilization is noninvasive and frameless.

PMID- 22973079
TI  - An analytic approach to the dosimetry of a new BEBIG (60)Co high-dose-rate
      brachytherapy source.
AB  - We present a simple analytic tool for calculating the dose rate distribution in
      water for a new BEBIG high-dose-rate (HDR) (60)Co brachytherapy source. In the
      analytic tool, we consider the active source as a point located at the geometric
      center of the (60)Co material. The influence of the activity distribution in the
      active volume of the source is taken into account separately by use of the line
      source-based geometric function. The exponential attenuation of primary (60)Co
      photons by the source materials ((60)Co and stainless-steel) is included in the
      model. The model utilizes the point-source-based function, f(r) that represents
      the combined effect of the exponential attenuation and scattered photons in
      water. We derived this function by using the published radial dose function for a
      point (60)Co source in an unbounded water medium of radius 50 cm. The attenuation
      coefficients for (60)Co and the stainless-steel encapsulation materials are
      deduced as best-fit parameters that minimize the different.

PMID- 22973080
TI  - Discrepancies in determining electron energy for lumpectomy boost treatment.
AB  - The aim of this study was to compare lumpectomy cavity depth measurements
      obtained through ultrasound (U/S) and retrospective computed tomography (CT).
      Twenty-five patients with stage T1-2 invasive breast cancer formed the cohort of
      this study. Their U/S and CT measurements were converted into electron energy and
      compared. The mean U/S depth was 3.6 +/- 1.3 cm, while the mean CT depth was 4.9
      +/- 1.9 cm; the listed error ranges are one standard deviation. Electron energies
      for treatment ranged from 6 MeV to 12 MeV based on the U/S determination. There
      was no significant correlation between cavity depths measured by U/S and CT
      (R(2)= 0.459, P < 0.002). Furthermore, only 20% of CT-based electron energy
      determinations matched the corresponding U/S determinations. This ratio increased
      to 40% when taking into account an upper limit based on the depth of organs at
      risk below the cavity. The study shows that there is a significant discrepancy
      between cavity depths determined by U/S and CT. It also supports the concept that
      post-lumpectomy radiotherapy boosts should be tailored according to the needs and
      comfort of individual practices and institutions.

PMID- 22973081
TI  - Commissioning and initial acceptance tests for a commercial convolution dose
      calculation algorithm for radiotherapy treatment planning in comparison with
      Monte Carlo simulation and measurement.
AB  - In this study the commissioning of a dose calculation algorithm in a currently
      used treatment planning system was performed and the calculation accuracy of two
      available methods in the treatment planning system i.e., collapsed cone
      convolution (CCC) and equivalent tissue air ratio (ETAR) was verified in tissue
      heterogeneities. For this purpose an inhomogeneous phantom (IMRT thorax phantom)
      was used and dose curves obtained by the TPS (treatment planning system) were
      compared with experimental measurements and Monte Carlo (MCNP code) simulation.
      Dose measurements were performed by using EDR2 radiographic films within the
      phantom. Dose difference (DD) between experimental results and two calculation
      methods was obtained. Results indicate maximum difference of 12% in the lung and
      3% in the bone tissue of the phantom between two methods and the CCC algorithm
      shows more accurate depth dose curves in tissue heterogeneities. Simulation
      results show the accurate dose estimation by MCNP4C in soft tissue region of the
      phantom and also better results than ETAR method in bone and lung tissues.

PMID- 22973082
TI  - Computed organ doses to an Indian reference adult during brachytherapy treatment
      of esophagus, breast, and neck cancers.
AB  - This study aims to generate the normalized mean organ dose factors (mGy min(-1)
      GBq(-1)) to healthy organs during brachytherapy treatment of esophagus, breast,
      and neck cancers specific to the patient population in India. This study is in
      continuation to the earlier published studies on the estimation of organ doses
      during uterus brachytherapy treatments. The results are obtained by Monte Carlo
      simulation of radiation transport through MIRD type anthropomorphic mathematical
      phantom representing reference Indian adult with (192)Ir and (60)Co high dose
      rate sources in the esophagus, breast, and neck of the phantom. The result of
      this study is compared with a published computational study using voxel-based
      phantom model. The variation in the organ dose of this study to the published
      values is within 50%.

PMID- 22973083
TI  - The influence of the patient size and geometry on cone beam-computed tomography
      hounsfield unit.
AB  - The objective of this work is to study the influence of the patient size and
      geometry on CBCT Hounsfield Unit and the accuracy of calibration Hounsfield Unit
      to electron density (HU-ED) using patient specific HU-ED mapping method for dose
      calculation. Two clinical cases, namely nasopharyngeal carcinoma (NPC) case and
      prostate case for 4 patients with different size and geometry were enrolled to
      assess the impact of size and geometry on CBCT Hounsfield Unit. The accuracy of
      the patient specific HU-ED mapping method was validated by comparing dose
      distributions based on planning CT and CBCT, dose-volume based indices and the
      digitally reconstructed radiograph (DRR) by analyzing their line profile plots.
      Significant differences in Hounsfield unit and line profile plots were found for
      NPC and prostate cases. The doses computed based on planning CT data sets and
      CBCT datasets for both clinical cases agree to within 1% for planning target
      volumes and 3% for organs at risk. The data shows that there are high dependence
      of HU on patient size and geometry; thus, the use of one CBCT HU-ED calibration
      curve made of one size and geometry will not be accurate for use with a patient
      of different size and geometry.

PMID- 22973084
TI  - Pocket-size solid-state iPOD and flash drives for gigabyte storage, display and
      transfer of digital medical images: Technology Update.

PMID- 22973085
TI  - Improving adherence to guidelines for the diagnosis and management of pelvic
      inflammatory disease: a systematic review.
AB  - BACKGROUND: Evidence suggests adherence to clinical guidelines for pelvic
      inflammatory disease (PID) diagnosis and management is suboptimal. We
      systematically reviewed the literature for studies describing strategies to
      improve the adherence to PID clinical guidelines. METHODS: The databases MEDLINE
      and EMBASE, and reference lists of review articles were searched from January
      2000 to April 2012. Only studies with a control group were included. RESULTS: An
      interrupted time-series study and two randomised controlled trials (RCTs) were
      included. The interrupted time-series found that following a multifaceted patient
      and practitioner intervention (practice protocol, provision of antibiotics on
      site, written instructions for patients, and active followup), more patients
      received the recommended antibiotics and attended for followup. One RCT found a
      patient video on PID self-care did not improve medication compliance and
      followup. Another RCT found an abbreviated PID treatment guideline for health
      practitioners improved their management of PID in hypothetical case scenarios but
      not their diagnosis of PID. CONCLUSION: There is limited research on what
      strategies can improve practitioner and patient adherence to PID diagnosis and
      management guidelines. Interventions that make managing PID more convenient, such
      as summary guidelines and provision of treatment on-site, appear to lead to
      better adherence but further empirical evidence is necessary.

PMID- 22973086
TI  - Macular hole surgery with short-acting gas and short-duration face-down
      positioning.
AB  - PURPOSE: To report on the outcomes of vitrectomy and sulfur hexafluoride (SF(6))
      gas tamponade for idiopathic macular holes with 2 days of face-down positioning.
      PATIENTS AND METHODS: This was a prospective, nonrandomized, observational
      sequential case-series study on 23 consecutive patients receiving macular hole
      surgery using 20% SF(6) and advised to stay in a face-down position for 2 days
      postoperatively (SF(6) group). These patients were compared to 23 consecutive
      patients who had previously undergone macular hole surgery, had received 14%
      C(3)F(8), and were advised to maintain a face-down position for 2 days (C(3)F(8)
      group). Patients in both groups underwent vitrectomy, internal limiting membrane
      peeling, and fluid gas exchange using either SF(6) or C(3)F(8.) Preoperative and
      postoperative data included best corrected visual acuity recorded in LogMAR
      units, slit-lamp biomicroscopy, and optical coherence tomography. RESULTS: At a 6
      month follow-up, macular hole closure was noted in 23/23 eyes (100%) and in 22/23
      eyes (96%) in the SF(6) and C(3)F(8) groups, respectively. The improvement in
      visual acuity (measured through Snellen acuity lines both preoperatively until 6
      months postoperatively) was 4.08 +/- 2.31 (95% confidence interval [CI]: 3.08
      5.08) for the SF(6) group and 2.87 +/- 2.30 (95% CI: 1.87-3.86) for the C(3)F(8)
      group; this difference was not statistically significant (P = 0.06). CONCLUSION:
      Vitrectomy with internal limiting membrane peeling and a short-acting gas
      tamponade using SF(6) with posture limitation for 2 days may give a high success
      rate in macular hole surgery.

PMID- 22973087
TI  - Comparative study of 1+PRN ranibizumab versus bevacizumab in the clinical
      setting.
AB  - PURPOSE: We compared the efficacy of intravitreal ranibizumab and bevacizumab for
      treating neovascular age-related macular degeneration using an on-demand regimen.
      METHODS: A total of 186 wet age-related macular degeneration eyes of 186
      treatment-naive patients were compared retrospectively (67 eyes treated with
      ranibizumab with 91 treated with bevacizumab). At baseline, mean age, best
      corrected visual acuity, and angiographic lesion types were similar in both
      groups. Best corrected visual acuity and ocular coherence tomography were
      evaluated. RESULTS: Sixty eyes treated with ranibizumab and 85 eyes treated with
      bevacizumab completed a 12-month evaluation. At 12 months, mean best corrected
      visual acuity increased by +6.65 letters with ranibizumab treatment and by +5.59
      with bevacizumab treatment (P = 0.64). Visual acuity improved by >=15 letters in
      15 eyes treated with ranibizumab and in 21 eyes treated with bevacizumab (P =
      0.75). An overall reduction in ocular coherence tomography central thickness
      occurred for all time points. The mean number of injections per eye was 5.97 with
      ranibizumab and 5.92 with bevacizumab (P = 0.90). CONCLUSION: Intravitreal
      therapies with ranibizumab or bevacizumab have similar visual and anatomical
      results. These results confirm those of comparison of Age-Related Macular
      Degeneration Treatment Trials in as-needed cohorts in clinical practice.
      Randomized long-term clinical trials are necessary to examine the systemic safety
      of these treatments.

PMID- 22973089
TI  - Vitrectomy for optic disc pit-associated maculopathy with or without preoperative
      posterior vitreous detachment.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of pars plana
      vitrectomy for the treatment of optic disc pit-associated maculopathy with or
      without preoperative posterior vitreous detachment. METHODS: We reviewed the
      clinical records of four consecutive patients who underwent pars plana vitrectomy
      in one eye for the treatment of optic disc pit-associated maculopathy, with an
      emphasis on the preoperative condition of the posterior hyaloid membrane.
      RESULTS: Two of four eyes were confirmed to have an attached posterior hyaloid
      membrane, which was subsequently removed during surgery. Following vitrectomy,
      these two eyes experienced an improvement in visual acuity with complete retinal
      attachment of the macula. However, the other two eyes, which already had a
      posterior vitreous detachment at the time of surgery, showed a decrease in visual
      acuity with persistent maculopathy postoperatively. CONCLUSION: Pars plana
      vitrectomy for optic disc pit-associated maculopathy was beneficial for improving
      visual acuity in two eyes without preoperative posterior vitreous detachment but
      not in two eyes with preoperative posterior vitreous detachment. Our study
      suggests that preoperative assessment of a posterior hyaloid membrane is
      clinically important in predicting the surgical outcome of optic disc pit
      associated maculopathy.

PMID- 22973088
TI  - Clinical and differential utility of VEGF inhibitors in wet age-related macular
      degeneration: focus on aflibercept.
AB  - Age-related macular degeneration (AMD) has become a major public health problem
      and a leading cause of blindness in industrialized nations. AMD results from the
      ageing eye's inability to metabolize and dispose completely of photoreceptor
      outer segments and other waste products. As a result, lipids, particularly
      apolipoproteins, accumulate within Bruch's membrane, leading to chronic ischemia
      and inflammation. The subsequent upregulation of inflammatory cytokines and
      growth factors, including vascular endothelial growth factor (VEGF), induces the
      growth of neovascular membranes from the choriocapillaris into the subretinal or
      subretinal pigment epithelium spaces. To counter this, intravitreally
      administered drugs (pegaptanib, bevacizumab, ranibizumab) that specifically
      target VEGF have become the standard treatment for exudative AMD. Aflibercept, a
      recently approved fusion protein, binds to all isoforms of both VEGF-A and
      placental growth factor with high affinity. Phase III trials showed that monthly
      or every other month injections of aflibercept prevent vision loss (fewer than 15
      letters) in 95% of patients. Additionally, aflibercept injections every 4 or 8
      weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable
      with those achieved with monthly ranibizumab. After one year of regularly
      administered aflibercept injections, patients required an average of only 4.2
      injections during the second year. Aflibercept promises to decrease the injection
      frequency required for many patients and appears to serve as an effective
      "salvage" therapy for patients who respond poorly to other anti-VEGF drugs.

PMID- 22973090
TI  - Ex vivo laser confocal microscopy findings of cultured Acanthamoeba trophozoites.
AB  - PURPOSE: The purpose of the current study was to investigate ex vivo laser
      confocal microscopic findings of cultured Acanthamoeba trophozoites obtained from
      Acanthamoeba keratitis patients. METHODS: Eight cultured samples of Acanthamoeba
      trophozoites from eight eyes of seven patients (mean age, 26.9 years; age range,
      18-52 years) were used. Seven samples were from corneal scrapings of Acanthamoeba
      keratitis patients and one sample was from the solution in a soft contact lens
      case. Ex vivo laser confocal microscopy was performed to qualitatively evaluate
      the shape and degree of light reflection of the living Acanthamoeba trophozoites.
      RESULTS: Ex vivo laser confocal microscopy demonstrated highly reflective, high
      contrast Acanthamoeba trophozoites with no walls (mean size, 25.4 MUm; range,
      17.1-58.5 MUm). The shapes of the trophozoites were highly pleomorphic, and some
      showed characteristic acanthopodia by laser confocal microscopy. CONCLUSION: Ex
      vivo laser confocal microscopy was effective in demonstrating cultured
      Acanthamoeba trophozoites of various shapes and sizes. The observations of the
      current study may be helpful when similar structures are identified under in vivo
      conditions.

PMID- 22973091
TI  - Exploring prospects of novel drugs for tuberculosis.
AB  - Tuberculosis remains a disease with an enormous impact on public health
      worldwide. With the continuously increasing epidemic of drug-resistant
      tuberculosis, new drugs are desperately needed. However, even for the treatment
      of drug-sensitive tuberculosis, new drugs are required to shorten the treatment
      duration and thereby prevent development of drug resistance. Within the past ten
      years, major advances in tuberculosis drug research have been made, leading to a
      considerable number of antimycobacterial compounds which are now in the pipeline.
      Here we discuss a number of these novel promising tuberculosis drugs, as well as
      the discovery of two new potential drug targets for the development of novel
      effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein
      kinase G pathways. Protein kinase G is secreted by mycobacteria and is
      responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is
      responsible for activating the phosphatase, calcineurin, and thereby preventing
      phagosome-lysosome fusion within the macrophage. Blocking these two pathways may
      lead to rapid killing of mycobacteria.

PMID- 22973092
TI  - Once-daily NVA237 improves exercise tolerance from the first dose in patients
      with COPD: the GLOW3 trial.
AB  - INTRODUCTION: Exercise limitation, dynamic hyperinflation, and exertional dyspnea
      are key features of symptomatic chronic obstructive pulmonary disease (COPD). We
      assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long
      acting muscarinic antagonist, on exercise tolerance in patients with moderate to
      severe COPD. METHODS: Patients were randomized to a cross-over design of once
      daily NVA237 50 MUg or placebo for 3 weeks, with a 14-day washout. Exercise
      endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes
      from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under
      exercise (Borg scales), and transition dyspnea index were measured on Days 1 and
      21 of treatment. The primary endpoint was endurance time during a submaximal
      constant-load cycle ergometry test on Day 21. RESULTS: A total of 108 patients
      were randomized to different treatment groups (mean age, 60.5 years; mean post
      bronchodilator, forced expiratory volume in 1 second [FEV(1)] 57.1% predicted).
      Ninety-five patients completed the study. On Day 21, a 21% difference in
      endurance time was observed between patients treated with NVA237 and those
      treated with placebo (P < 0.001); the effect was also significant from Day 1,
      with an increase of 10%. Dynamic IC at exercise isotime and trough FEV(1) showed
      significant and clinically relevant improvements from Day 1 of treatment that
      were maintained throughout the study. This was accompanied by inverse decreases
      in residual volume and functional residual capacity. NVA237 was superior to
      placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and
      exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale
      at isotime). The safety profile of NVA237 was similar to that of the placebo.
      CONCLUSION: NVA237 50 MUg once daily produced immediate and significant
      improvement in exercise tolerance from Day 1. This was accompanied by sustained
      reductions in lung hyperinflation (indicated by sustained and significant
      improvements in IC at isotime), and meaningful improvements in trough FEV(1) and
      dyspnea. Improvements in exercise endurance increased over time, suggesting that
      mechanisms beyond improved lung function may be involved in enhanced exercise
      tolerance. (ClinicalTrials.gov Identifier: NCT01154127).

PMID- 22973094
TI  - Associations between isokinetic muscle strength, high-level functional
      performance, and physiological parameters in patients with chronic obstructive
      pulmonary disease.
AB  - High-level activities are typically not performed by patients with chronic
      obstructive pulmonary disease (COPD), which results in reduced functional
      performance; however, the physiological parameters that contribute to this
      reduced performance are unknown. The aim of this study was to determine the
      relationships between high-level functional performance, leg muscle
      strength/power, aerobic power, and anaerobic power. Thirteen patients with COPD
      underwent an incremental maximal cardiopulmonary exercise test, quadriceps
      isokinetic dynamometry (isometric peak torque and rate of torque development;
      concentric isokinetic peak torque at 90 degrees /sec, 180 degrees /sec, and 270
      degrees /sec; and eccentric peak torque at 90 degrees /sec), a steep ramp
      anaerobic test (SRAT) (increments of 25 watts every 10 seconds), and three
      functional measures (timed up and go [TUG], timed stair climb power [SCPT], and
      30-second sit-to-stand test [STS]). TUG time correlated strongly (P < 0.05) with
      all muscle strength variables and with the SRAT. Isometric peak torque was the
      strongest determinant of TUG time (r = -0.92). SCPT and STS each correlated with
      all muscle strength variables except concentric at 270 degrees /sec and with the
      SRAT. The SRAT was the strongest determinant of SCPT (r = 0.91), and eccentric
      peak torque at 90 degrees /sec was most significantly associated with STS (r =
      0.81). Performance on the SRAT (anaerobic power); slower-velocity concentric,
      eccentric, and isometric contractions; and rate of torque development are
      reflected in all functional tests, whereas cardiopulmonary exercise test
      performance (aerobic power) was not associated with any of the functional or
      muscle tests. High-level functional performance in patients with COPD is
      associated with physiological parameters that require high levels of muscle force
      and anaerobic work rates.

PMID- 22973095
TI  - Interaction between submicron COD crystals and renal epithelial cells.
AB  - OBJECTIVES: This study aims to investigate the adhesion characteristics between
      submicron calcium oxalate dihydrate (COD) with a size of 150 +/- 50 nm and
      African green monkey kidney epithelial cells (Vero cells) before and after
      damage, and to discuss the mechanism of kidney stone formation. METHODS: Vero
      cells were oxidatively injured by hydrogen peroxide to establish a model of
      injured cells. Scanning electron microscopy was used to observe Vero-COD
      adhesion. Inductively coupled plasma emission spectrometry was used to
      quantitatively measure the amount of adhered COD microcrystals. Nanoparticle size
      analyzer and laser scanning confocal microscopy were performed to measure the
      change in the zeta potential on the Vero cell surface and the change in
      osteopontin expression during the adhesion process, respectively. The level of
      cell injury was evaluated by measuring the changes in malonaldehyde content, and
      cell viability during the adhesion process. RESULTS: The adhesion capacity of
      Vero cells in the injury group to COD microcrystals was obviously stronger than
      that of Vero cells in the control group. After adhesion to COD, cell viability
      dropped, both malonaldehyde content and cell surface zeta potential increased,
      and the fluorescence intensity of osteopontin decreased because the osteopontin
      molecules were successfully covered by COD. Submicron COD further damaged the
      cells during the adhesion process, especially for Vero cells in the control
      group, leading to an elevated amount of attached microcrystals. CONCLUSION:
      Submicron COD can further damage injured Vero cells during the adhesion process.
      The amount of attached microcrystals is proportional to the degree of cell
      damage. The increased amount of microcrystals that adhered to the injured
      epithelial cells plays an important role in the formation of early-stage kidney
      stones.

PMID- 22973093
TI  - Muscle function in COPD: a complex interplay.
AB  - The skeletal muscles play an essential role in life, providing the mechanical
      basis for respiration and movement. Skeletal muscle dysfunction is prevalent in
      all stages of chronic obstructive pulmonary disease (COPD), and significantly
      influences symptoms, functional capacity, health related quality of life, health
      resource usage and even mortality. Furthermore, in contrast to the lungs, the
      skeletal muscles are potentially remedial with existing therapy, namely exercise
      training. This review summarizes clinical and laboratory observations of the
      respiratory and peripheral skeletal muscles (in particular the diaphragm and
      quadriceps), and current understanding of the underlying etiological processes.
      As further progress is made in the elucidation of the molecular mechanisms of
      skeletal muscle dysfunction, new pharmacological therapies are likely to emerge
      to treat this important extra-pulmonary manifestation of COPD.

PMID- 22973096
TI  - Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for
      enhanced topical delivery of ibuprofen.
AB  - INTRODUCTION: During recent years, there has been growing interest in the use of
      nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a
      transparent mixture of oil, surfactant and water with a very low viscosity,
      usually the product of its high water content. The present study investigated the
      modification of nanoemulsions with different hydrocolloid gums, to enhanced drug
      delivery of ibuprofen. The in vitro characterization of the initial and modified
      nanoemulsions was also studied. METHODS: A palm kernel oil esters nanoemulsion
      was modified with different hydrocolloid gums for the topical delivery of
      ibuprofen. Three different hydrocolloids (gellan gum, xanthan gum, and
      carrageenan) were selected for use. Ternary phase diagrams were constructed using
      palm kernel oil esters as the oil, Tween 80 as the surfactant, and water.
      Nanoemulsions were prepared by phase inversion composition, and were gradually
      mixed with the freshly prepared hydrocolloids. The initial nanoemulsion and
      modified nanoemulsions were characterized. The abilities of the nanoemulsions to
      deliver ibuprofen were assessed in vitro, using a Franz diffusion cell fitted
      with rat skin. RESULTS: No significant changes were observed in droplet size (~16
      20 nm) but a significant difference in polydispersity indexes were observed
      before and after the modification of nanoemulsions using gellan gum, carrageenan,
      and xanthan gum. The zeta potentials of the initial nanoemulsions (-11.0 mV)
      increased to -19.6 mV, -13.9 mV, and -41.9 mV, respectively. The abilities of
      both the initial nanoemulsion (T802) and the modified nanoemulsion to deliver
      ibuprofen through the skin were evaluated in vitro, using Franz diffusion cells
      fitted with rat skin. The in vitro permeation data showed that the modified
      nanoemulsion (Kp value of 55.4 * 10(-3) cm . h(-1)) increased the permeability of
      ibuprofen 4.40 times over T802 (Kp value of 12.6 * 10(-3) cm . h(-1)) (P < 0.05).
      CONCLUSION: The modified nanoemulsion may be a promising vehicle to enhance the
      permeation of ibuprofen for topical delivery.

PMID- 22973097
TI  - Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth
      factor receptor-active targeting ligand for doxorubicin.
AB  - BACKGROUND: This study was performed to develop a functional poly(D,L-lactide-co
      glycolide)-poly(ethylene glycol) (PLGA-PEG)-bearing amino-active end group for
      peptide conjugation. METHODS AND RESULTS: PLGA was preactivated following by
      copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer
      bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 *
      10-8 mol/L, and the half-effective inhibition concentration (IC50) of the
      prepared PLGA-PEG nanoparticles was >100 mg/mL, which was much higher than that
      of PLGA nanoparticles (1.02 +/- 0.37 mg/mL). The amphiphilic properties of PLGA
      PEG spontaneously formed a core-shell conformation in the aqueous environment,
      and this special feature provided the amino group on the PEG chain scattered on
      the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The
      peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than
      peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of
      epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA
      PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although
      the rate of release of doxorubicin from both nanoparticles was similar, drug
      release at pH 4.0 (500 U lipase) was faster than at pH 7.4. The IC50 of
      doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05
      +/- 0.03 MUg/mL) was much lower (by 62.4-fold) than that of peptide-free PLGA-PEG
      nanoparticles (3.12 +/- 1.44 MUg/mL). CONCLUSION: This in vivo biodistribution
      study in SKOV3 tumor-bearing mice was further promising in that accumulation of
      doxorubicin in tumor tissue was in the order of peptide-conjugated PLGA-PEG
      nanoparticles > peptide-free PLGA-PEG nanoparticles > doxorubicin solution.

PMID- 22973098
TI  - Minocycline hydrochloride nanoliposomes inhibit the production of TNF-alpha in
      LPS-stimulated macrophages.
AB  - BACKGROUND: As an adjunctive treatment of chronic periodontitis, it seems that
      the application of periocline or the other antimicrobials is effective against
      periodontopathogens. In this study, nanoliposomes were investigated as carriers
      of minocycline hydrochloride and the inhibition effects of minocycline
      hydrochloride nanoliposomes on the proliferation and lipopolysaccharide (LPS)
      stimulated production of tumor necrosis factor-alpha (TNF-alpha) of macrophages
      were elucidated. METHODS: After stimulation with 10 MUg/mL LPS, murine
      macrophages (ANA-1) were treated with 10, 20, 40, 50 and 70 MUg/mL 2% minocycline
      hydrochloride nanoliposomes, minocycline hydrochloride solution, and periocline
      for 6, 12, 24, 48 and 60 hours, respectively. A tetrazolium (MTT) assay was used
      to evaluate macrophages cell proliferation rate and the levels of TNF-alpha mRNA
      were measured by SYBR Green Real Time PCR. RESULTS: Ten to 70 MUg/mL 2%
      minocycline hydrochloride nanoliposomes, minocycline hydrochloride solution, and
      periocline showed dose- and time-dependent inhibition of ANA-1 proliferation.
      Minocycline hydrochloride nanoliposomes showed dose- and ratio-dependent
      inhibition of LPS-stimulated TNF-alpha secretion of ANA-1. The inhibition effect
      of 10 MUg/mL minocycline hydrochloride nanoliposomes was significantly better
      than that of two positive control groups, and equated to that of 60 or 70 MUg/mL
      periocline. The expression of TNF-alpha mRNA in experimental group continued to
      reduce linearly with time. CONCLUSION: All three preparations of minocycline
      hydrochloride showed dose- and time-dependent inhibition of proliferation of ANA
      1. Minocycline hydrochloride nanoliposomes have stronger and longer inhibition
      effect on LPS-stimulated TNF-alpha secretion of macrophages cell than minocycline
      hydrochloride solution and periocline.

PMID- 22973099
TI  - Targeted dual-color silica nanoparticles provide univocal identification of
      micrometastases in preclinical models of colorectal cancer.
AB  - BACKGROUND AND METHODS: Despite the recent introduction of targeted bio-drugs,
      the scarcity of successful therapeutic options for advanced colorectal cancer
      remains a limiting factor in patient management. The efficacy of curative
      surgical interventions can only be extended through earlier detection of
      metastatic foci, which is dependent on both the sensitivity and specificity of
      the diagnostic tools. RESULTS: We propose a high-performance imaging platform
      based on silica-poly(ethylene glycol) nanoparticles doped with rhodamine B and
      cyanine 5. Simultaneous detection of these dyes is the basis for background
      subtraction and signal amplification, thus providing high-sensitivity imaging.
      The functionalization of poly(ethylene glycol) tails on the external face of the
      nanoparticles with metastasis-specific peptides guarantees their homing to and
      accumulation at target tissues, resulting in specific visualization, even of
      submillimetric metastases. CONCLUSIONS: The results reported here demonstrate
      that our rationally designed modular nanosystems have the ability to produce a
      breakthrough in the detection of micrometastases for subsequent translation to
      clinics in the immediate future.

PMID- 22973100
TI  - Intraperitoneal injection of magnetic Fe3O4-nanoparticle induces hepatic and
      renal tissue injury via oxidative stress in mice.
AB  - Because of its unique magnetic properties, the iron oxide (Fe3O4) nanoparticle
      has been widely exploited and its application in various fields has promised
      immense benefits. However, doubts exist over the use of Fe3O4-nanoparticles in
      human beings. Thus, the aim of the current study was to find out the potential
      safety range of medical use. Twenty-five Kunming mice were exposed to Fe3O4
      nanoparticles via intraperitoneal injection daily for 1 week at doses of 0, 5,
      10, 20, and 40 mg/kg. Hepatic and renal tissues were sliced for physiological
      observation. Injuries were observed in the high-dose groups (20 and 40 mg/kg)
      compared with the control group (0 mg/kg). Biomarkers of reactive oxygen species,
      glutathione, malondialdehyde, DNA-protein crosslinks, and 8-hydroxy-2'
      deoxyguanosine in the hepatic and renal tissues were detected. Injury to tissues
      and oxidative damage to cells at the molecular level was found. The safest dose
      recommended from the results of this study is 5 mg/kg, as we believe this to be
      an upper limit balancing the benefits and risks for sub-long-term exposure.

PMID- 22973101
TI  - Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal
      phosphate.
AB  - BACKGROUND: Bioconjugates of a polyamidoamine (PAMAM) G3 dendrimer and an
      aldehyde were synthesized as carriers for vitamins A and B6, and the
      bioavailability of these vitamins for skin nutrition was investigated. METHODS:
      Nuclear magnetic resonance (NMR) and ultraviolet-visible methods were used to
      characterize the structure of the bioconjugates and for monitoring release of
      pyridoxal (Pyr) and pyridoxal phosphate (PLP) from these bioconjugates in vitro.
      A skin model permeation of bioconjugates was also studied in a Franz chamber.
      RESULTS: A transdermal G3 PAMAM dendrimer was used to synthesize bioconjugates
      with trans-retinal (Ret), pyridoxal (Pyr), or PLP. These nanomolecules,
      containing up to four covalently linked Ret, Pyr, or PLP (G3(4Ret), G3(4Pyr), and
      G3(4PLP)), were able to permeate the skin, as demonstrated in vitro using a model
      skin membrane. PLP and Pyr bound to a macromolecular vehicle were active
      cofactors for glutamic pyruvic transaminase, as shown by 1H NMR spectral
      monitoring of the progress of the L-alanine + alpha-ketoglutarate -> glutamic
      acid + pyruvic acid reaction. CONCLUSION: PAMAM-PLP, PAMAM-Pyr, and PAMAM-Ret
      bioconjugates are able to permeate the skin. PLP and Pyr are available as
      cofactors for glutamic pyruvic transaminase.

PMID- 22973102
TI  - Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium.
AB  - A significant need exists for orthopedic implants that can intrinsically resist
      bacterial colonization. In this study, three biomaterials that are used in spinal
      implants--titanium (Ti), polyether-ether-ketone (PEEK), and silicon nitride
      (Si3N4)--were tested to understand their respective susceptibility to bacterial
      infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas
      aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface
      chemistry, wettability, and nanostructured topography of respective biomaterials,
      and the effects on bacterial biofilm formation, colonization, and growth were
      investigated. Ti and PEEK were received with as-machined surfaces; both materials
      are hydrophobic, with net negative surface charges. Two surface finishes of Si3N4
      were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of
      Si3N4 is hydrophilic, with a net positive charge. A decreased biofilm formation
      was found, as well as fewer live bacteria on both the as-fired and polished
      Si3N4. These differences may reflect differential surface chemistry and surface
      nanostructure properties between the biomaterials tested. Because protein
      adsorption on material surfaces affects bacterial adhesion, the adsorption of
      fibronectin, vitronectin, and laminin on Ti, PEEK, and Si3N4 were also examined.
      Significantly greater amounts of these proteins adhered to Si3N4 than to Ti or
      PEEK. The findings of this study suggest that surface properties of biomaterials
      lead to differential adsorption of physiologic proteins, and that this phenomenon
      could explain the observed in-vitro differences in bacterial affinity for the
      respective biomaterials. Intrinsic biomaterial properties as they relate to
      resistance to bacterial colonization may reflect a novel strategy toward
      designing future orthopedic implants.

PMID- 22973103
TI  - Preparation of bioactive interferon alpha-loaded polysaccharide nanoparticles
      using a new approach of temperature-induced water phase/water-phase emulsion.
AB  - The aim of this study was to develop a temperature-induced polyethylene glycol
      (PEG) water phase/polysaccharide water-phase emulsion approach for preparing
      interferon alpha-2b (IFNalpha-2b)-loaded polysaccharide nanoparticles. IFNalpha
      2b was first added to a mixture of an aqueous solution of PEG and polysaccharide.
      The mixture solution was stirred in a magnetic stirrer at a rate of 2000 rpm for
      45 seconds at 0 degrees C +/- 0.5 degrees C. The solution was then prefrozen at
      different temperatures. The polysaccharide and IFNalpha-2b partitioned in the
      polysaccharide phase were preferentially separated out as the dispersed phase
      from the mixture solution during the prefreezing process. Then the prefrozen
      sample was freeze-dried to powder form. In order to remove the PEG, the powder
      was washed with dichloromethane. Once IFNalpha-2b was loaded into the
      polysaccharide nanoparticles, these nanoparticles could gain resistance to vapor
      water and water-oil interfaces to protect IFNalpha-2b. The antiviral activity of
      the polysaccharide nanoparticles in vitro was highly preserved (above 97%), while
      the antiviral activity of IFNalpha-2b-loaded polysaccharide nanoparticles using
      the control water-in-oil-in-water method was only 71%. The antiviral activity of
      the IFNalpha-2b from blood samples was also determined on the basis of the
      activity to inhibit the cytopathic effects of the Sindbis virus on Follicular
      Lymphoma cells (FL). The antiviral activity in vivo was also highly preserved
      (above 97%). These polysaccharide nanoparticles could be processed to different
      formulations according to clinical requirements.

PMID- 22973104
TI  - OPLS statistical model versus linear regression to assess sonographic predictors
      of stroke prognosis.
AB  - The objective of the present study was to assess the comparable applicability of
      orthogonal projections to latent structures (OPLS) statistical model vs
      traditional linear regression in order to investigate the role of trans cranial
      doppler (TCD) sonography in predicting ischemic stroke prognosis. The study was
      conducted on 116 ischemic stroke patients admitted to a specialty neurology ward.
      The Unified Neurological Stroke Scale was used once for clinical evaluation on
      the first week of admission and again six months later. All data was primarily
      analyzed using simple linear regression and later considered for multivariate
      analysis using PLS/OPLS models through the SIMCA P+12 statistical software
      package. The linear regression analysis results used for the identification of
      TCD predictors of stroke prognosis were confirmed through the OPLS modeling
      technique. Moreover, in comparison to linear regression, the OPLS model appeared
      to have higher sensitivity in detecting the predictors of ischemic stroke
      prognosis and detected several more predictors. Applying the OPLS model made it
      possible to use both single TCD measures/indicators and arbitrarily dichotomized
      measures of TCD single vessel involvement as well as the overall TCD result. In
      conclusion, the authors recommend PLS/OPLS methods as complementary rather than
      alternative to the available classical regression models such as linear
      regression.

PMID- 22973105
TI  - Twelve-month, prospective, open-label study of repetitive transcranial magnetic
      stimulation for major depressive disorder in partial remission.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term effect of
      repetitive transcranial magnetic stimulation (rTMS) as adjunctive treatment in
      patients with partial remission of major depressive disorder. METHODS: This was a
      12-month, prospective, open-label study in patients meeting the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria
      for nonpsychotic major depressive disorder who responded to 8 weeks of medication
      treatment but did not reach remission. All patients were assigned to receive 10
      sessions of rTMS applied at the left dorsolateral prefrontal cortex. During the
      course of rTMS, the patients were still taking their usual medication. Patients
      were followed up for 12 months to determine the long-term antidepressant effect.
      RESULTS: There were nine patients (seven women and two men) who met the inclusion
      criteria and agreed to receive rTMS. The mean Hamilton rating scale for
      depression (HAM-D) score prior to treatment with rTMS was 12.89 +/- 2.15. At 12
      months after treatment, the mean HAM-D score was 6.45 +/- 1.67 using a Friedman
      test, and in patients with partial remission of major depressive disorder, the
      HAM-D score significantly decreased after treatment with rTMS at 12 months (P =
      0.001). Seven patients (77.78%) had reached the stage of remission (HAM-D < 8)
      after treating with rTMS at 12 months. There were no serious adverse events. One
      patient had vertigo after the first session of treatment and one patient felt
      scalp contractions during treatment, and both fully recovered within half an hour
      with no medical intervention. CONCLUSION: For patients with major depressive
      disorder in partial remission, high frequency rTMS at the left dorsolateral
      prefrontal cortex may provide benefits in adjunctive treatment with well
      tolerability. Also, follow-up findings show a long duration of benefit.

PMID- 22973106
TI  - Avanafil for treatment of erectile dysfunction: review of its potential.
AB  - Avanafil is a medication that was recently approved by the US Food and Drug
      Administration for the management of erectile dysfunction. Avanafil is a new
      phosphodiesterase type 5 inhibitor similar to sildenafil and tadalafil. Avanafil
      was studied in over 1300 patients during clinical trials, including patients with
      diabetes mellitus and those who had undergone radical prostatectomy, and was
      found to be more effective than placebo in all men who were randomized to the
      drug. The medication was studied with on-demand dosing that may occur after food
      and/or alcohol. Avanafil is dosed as 50 mg, 100 mg, or 200 mg tablets. Avanafil
      may differentiate itself from the other phosphodiesterase type 5 inhibitors with
      its quicker onset and higher specificity for phosphodiesterase type 5 versus
      other phosphodiesterase subtypes, but may lead to complications of therapy.

PMID- 22973107
TI  - Rivaroxaban in atrial fibrillation.
AB  - Warfarin is the traditional therapeutic option available to manage thromboembolic
      risk in atrial fibrillation. The hemorrhagic risk with warfarin depends mainly on
      the international normalized ratio (INR). Data from randomized controlled trials
      show that patients have a therapeutic INR (2.00-3.00) only 61%-68% of the time
      while taking warfarin, and this target is sometimes hard to establish. Many
      compounds have been developed in order to optimize the profile of oral
      anticoagulants. We focus on one of them, rivaroxaban, comparing it with novel
      alternatives, ie, dabigatran and apixaban. The indication for rivaroxaban in
      nonvalvular atrial fibrillation was evaluated in ROCKET-AF (Rivaroxaban-once
      daily, Oral, direct factor Xa inhibition Compared with vitamin K antagonism for
      prevention of stroke and Embolism Trial in Atrial Fibrillation). In this trial,
      rivaroxaban was associated with a 12% reduction in the incidence of the primary
      endpoint compared with warfarin (hazard ratio 0.88; 95% confidence interval [CI]
      0.74-1.03; P < 0.001 for noninferiority and P = 0.12 for superiority). However,
      patients remained in the therapeutic range for INR only 55% of the time, which is
      less than that in RE-LY (the Randomized Evaluation of Long-Term Anticoagulation
      Therapy, 64%) and in the ARISTOTLE trial (Apixaban for Reduction in Stroke and
      Other Thromboembolic Events in Atrial Fibrillation, 66%). This shorter time spent
      in the therapeutic range has been one of the main criticisms of the ROCKET-AF
      trial, but could actually reflect what happens in real life. In addition,
      rivaroxaban exhibits good pharmacokinetic and pharmacoeconomic properties. Novel
      anticoagulants are a viable and commercially available alternative to vitamin K
      antagonists nowadays for the prevention of thromboembolic complications in atrial
      fibrillation. Rivaroxaban is an attractive alternative, but the true picture of
      this novel compound in atrial fibrillation will only become available with more
      widespread use.

PMID- 22973108
TI  - A 3-year follow-up study of inpatients with lower limb ulcers: evidence of an
      obesity paradox?
AB  - OBJECTIVES: To determine whether body composition is related to long-term
      outcomes amongst vascular inpatients with lower limb ulcers. DESIGN: Prospective
      study with 3 years follow-up. MATERIALS AND METHODS: Body mass index (BMI), fat,
      and fat-free mass were measured and associations with readmission to hospital
      (number, cause, length of stay) and all-cause mortality were explored. RESULTS:
      Thirty patients (22 men, 8 women) participated in the study. Ten patients (33%)
      had a BMI >= 30 kg/m(2). 18/20 (90%) patients with a BMI < 30 kg/m(2) and 9/10
      (90%) patients with a BMI >= 30 kg/m(2) were admitted to hospital in the 3 years
      of follow-up. Patients with a BMI < 30 kg/m(2) were admitted more frequently,
      earlier and for longer compared to those with BMI >= 30 kg/m(2) but these did not
      reach statistical significance. The 3 year mortality rate for patients with BMI
      >= 30 kg/m(2) was 20% (n = 2/10) compared to 70% (n = 14/20) with a BMI < 30
      kg/m(2), P = 0.019. CONCLUSION: This preliminary study suggests that higher BMI
      may have a protective effect against mortality in vascular patients with lower
      limb ulcers. These findings contradict the universal acceptance that obesity
      leads to poor health outcomes. Further work is required to confirm these findings
      and explore some of the potential mechanisms for this effect.

PMID- 22973109
TI  - Health research barriers in the faculties of two medical institutions in India.
AB  - BACKGROUND: Health policy formation refers to the design of a conceptual
      framework to find possibilities, facilitate feasibilities, and identify strong
      and weak points, as well as insufficiencies, by research. Doing research should
      clarify qualities and standards for policy and decision-making to enable the
      success of development of health care in a country. Evaluation of the impact of
      health interventions is particularly poorly represented in public health
      research. This study attempted to identify barriers and facilitators of health
      research among faculty members in two major institutions in India, ie, the All
      India Institute of Medical Sciences (AIIMS) and the University College of Medical
      Sciences (UCMS) and Guru Tegh Bahadur (GTB) Hospital in Delhi. METHODS: The
      participants were asked to fill in a questionnaire that canvassed individual
      characteristics, ie, years of experience, place of work, academic rank, final
      educational qualification, work setting, educational group, primary activity, and
      number of publications in the previous 5 years. Barriers and facilitators were
      categorized into personal, resources, access, and administration groups. The data
      were processed using SPSS version 16, independent t-tests, Chi-square tests, and
      multivariate logistic regression. RESULTS: The total number of faculty members at
      both institutions was 599, 456 (76%) of whom participated in this study. The
      primary activities reported by faculty at UCMS (teaching) and Faculty at AIIMS
      reported (Research and Provision of health care services) as a major activity (P
      < 0.01). The majority of faculty members at UCMS and GTB Hospital were
      professors, whereas most of the faculty members at AIIMS were associate
      professors (P < 0.01). Of 47 barriers and facilitating factors, there were 26
      barriers and 21 facilitating factors at AIIMS and 39 barriers and eight
      facilitating factors at UCMS. Faculty members at UCMS had 6.572 times more
      barriers to health research than those at AIIMS. CONCLUSION: Close proximity
      between AIIMS and the Indian Council of Medical Research and the National Medical
      Library, housing, transport, and a good reference library with an adequate
      knowledge support system provided suitable opportunities for faculty members at
      AIIMS to do research. To overcome the barriers, institutions must have enough
      financial support, decreased nonessential clinical, laboratory, and service
      schedule duties on the part of faculty members, preparation of good and relevant
      statistical courses and workshops, and access to good statistical software
      packages.

PMID- 22973110
TI  - Short-term functional outcome in children with arthrogryposis multiplex congenita
      after multiple surgeries at an early age.
AB  - PURPOSE: The purpose of this study is to report our short-term functional outcome
      for 14 children with arthrogryposis multiplex congenita (AMC) who underwent
      multiple surgical procedures at an early age. METHODS: During the period 2002
      2010, 14 children (11 males and three females) with AMC underwent multiple
      surgical procedures to treat deformities of the lower and upper limbs. About 81
      procedures were performed, at a rate of 5.9 procedures per child. The mean age at
      the last follow-up was 5.9 years. The average follow-up period was 3.6 years
      (range, 1.5-6 years). The functional outcome assessment included walking ability
      and the activities of daily living for the upper limb function. RESULTS: At the
      last follow-up visit, six (43%) children (four males, two females) with a mean
      age of 8.3 years (range, 4-15) were independent walkers. Three children (males)
      with a mean age of 3.5 years (range, 2.5-5) were able to walk, but with support.
      One child (male), 3 years old, was a household ambulator. Three children (two
      males, one female) with a mean age of 4.2 years (range, 2.5-6) were nonfunctional
      ambulators. The last child (male) was nonambulatory at the age of 5 years.
      Activities of daily living were severely affected in the nonambulatory child. One
      child in the nonfunctional ambulators group had limitations in the activities of
      daily living; however, upper limb function was not affected in the remaining 12
      children. CONCLUSION: We believe that aggressive surgical treatment using
      multiple operations at an early age can improve the short-term functional and
      clinical outcomes of children with AMC.

PMID- 22973111
TI  - What is optimal timing for trauma team alerts? A retrospective observational
      study of alert timing effects on the initial management of trauma patients.
AB  - BACKGROUND: Trauma teams improve the initial management of trauma patients.
      Optimal timing of trauma alerts could improve team preparedness and performance
      while also limiting adverse ripple effects throughout the hospital. The purpose
      of this study was to evaluate how timing of trauma team activation and
      notification affects initial in-hospital management of trauma patients. METHODS:
      Data from a single hospital trauma care quality registry were matched with data
      from a trauma team alert log. The time from patient arrival to chest X-ray, and
      the emergency department length of stay were compared with the timing of trauma
      team activations and whether or not trauma team members received a preactivation
      notification. RESULTS: In 2009, the trauma team was activated 352 times; 269
      times met the inclusion criteria. There were statistically significant
      differences in time to chest X-ray for differently timed trauma team activations
      (P = 0.003). Median time to chest X-ray for teams activated 15-20 minutes
      prearrival was 5 minutes, and 8 minutes for teams activated <5 minutes before
      patient arrival. Timing had no effect on length of stay in the emergency
      department (P = 0.694). We found no effect of preactivation notification on time
      to chest X-ray (P = 0.474) or length of stay (P = 0.684). CONCLUSION: Proactive
      trauma team activation improved the initial management of trauma patients. Trauma
      teams should be activated prior to patient arrival.

PMID- 22973112
TI  - Expression of transient receptor potential channel 6 in cervical cancer.
AB  - BACKGROUND: Recent studies have reported that aberrant expression of transient
      receptor potential channel C6 (TRPC6) in a variety of human cancers is associated
      with aggressive behavior. However, the functional significance of TRPC6 in human
      cervical cancer is not known. This study was planned to detect whether TRPC6 is
      expressed in cervical cancer tissue and to evaluate the association between TPRC6
      expression and clinicopathologic features. METHODS: Tissue samples were collected
      from the West China Second UNIV Hospital of Sichuan University. TRPC6 expression
      was detected by quantitative real-time reverse transcription polymerase chain
      reaction and Western blotting. TRPC6 expression was evaluated by
      immunohistochemistry analysis of 40 cervical cancer specimens, and correlations
      were sought between elevated expression of TRPC6 and clinicopathologic features.
      RESULTS: Increased expression of TRPC6 was detected in 25 of the 40 cervical
      cancer samples. Positive cells found in cervical carcinomas were significantly
      increased in numbers compared with specimens without lymphovascular space
      invasion. Elevated expression of TRPC6 was neither related to International
      Federation of Gynecology and Obstetrics stage nor pelvic lymph metastases.
      Indeed, the clinicopathologic analysis indicated that overexpression of TRPC6 was
      significantly associated with lymphovascular space invasion. CONCLUSION: These
      results indicate that elevated expression of TRPC6 might be associated with an
      aggressive cervical cancer phenotype.

PMID- 22973113
TI  - Emerging treatment options for patients with recurrent advanced thymic epithelial
      tumors.
AB  - The purpose of this review article is to review recent advances in the treatment
      of advanced thymic epithelial tumors. These tumors are generally responsive to
      cytotoxic combination chemotherapy in the first-line setting. While newer agents
      have shown efficacy in the salvage setting, there is no one standard approach. A
      multitude of targeted agents have shown promise generally in case reports, though
      as of yet, nothing has shown consistent benefit. Because of the rarity of thymic
      epithelial tumors, clinical trial enrollment is difficult but nevertheless
      essential.

PMID- 22973114
TI  - Cost of human immunodeficiency virus infection in Italy, 2007-2009: effective and
      expensive, are the new drugs worthwhile?
AB  - BACKGROUND: In recent years, the increased efficacy and effectiveness of
      antiretroviral treatment has led to longer survival of patients infected with
      human immunodeficiency virus (HIV), but has also raised the question of what
      happens to consumption of resources. Early highly active antiretroviral treatment
      (HAART), management of hepatitis C virus (HCV) coinfection, and expensive newly
      marketed drugs may affect the economic sustainability of treatment from the point
      of view of the National Healthcare Services. The present study aimed to provide
      information on the economic burden of HIV-positive patients resident in the
      Lombardy region using a three-year time horizon. METHODS: This was a
      retrospective, observational, budget impact study, based on information collected
      for the period 2007-2009, including hospitalizations, outpatient services, and
      HAART and non-HAART drug utilization. Patients with confirmed HIV infection, aged
      >= 18 years, resident in the Lombardy region, and followed at the "L Sacco"
      Hospital in Milan from 2007 to 2009 were eligible. RESULTS: A total of 483
      patients (mean age 44.1 years) were included in the study. The mean CD4+ cell
      count increased over the study period from 462 +/- 242 cells/mm(3) in 2007, to
      513 +/- 267 cells/mm(3) in 2008, to 547 +/- 262 cells/mm(3) in 2009. In total,
      162 subjects (33.5%) were coinfected with HCV. Hospitalizations and HAART costs
      increased from 2007 to 2009, whereas outpatient visits and non-HAART drug costs
      decreased slightly over time. The total cost increase was also significant when
      limiting the analysis to experienced patients, HCV-negative patients, and
      experienced HCV-negative patients. CONCLUSION: CD4+ cell count, a major predictor
      of costs, increased over the study period. However, immunological improvement was
      achieved by greater expense in the short term. Whether this may be compensated by
      a long-term decrease in opportunistic infections and in the costs of management
      of HIV-related events is an area still to be investigated.

PMID- 22973115
TI  - Correlation between anthropometric indices at birth and developmental delay in
      children aged 4-60 months in Isfahan, Iran.
AB  - BACKGROUND: Advances in medical knowledge and treatment modalities have resulted
      in an increased survival rate for high-risk infants. This increased number of
      survivors enables study of the future development of these children. Other than
      infection and trauma, developmental and behavioral problems are the most common
      medical problems among such children. This study sought correlations between
      anthropometric indices at birth and developmental delay in children aged 4-60
      months who visited health service centers affiliated with the Isfahan University
      of Medical Sciences in 2010. METHODS: In this descriptive, correlational study,
      401 children aged 4-60 months and visiting health service centers were selected
      using a multistage method. Anthropometric indices at birth were collected from
      their health care records, and developmental status was measured using the Ages
      and Stages Questionnaire, the validity (0.84) and reliability (0.94) of which
      were obtained from a previous study. RESULTS: The mean age of the children in the
      normal group was 17.33 +/- 13.18 months and that in the developmental delay group
      was 29.92 +/- 19.19 months. Most children in the normal group were female (56%)
      and in the developmental delay group were male (55.2%). No correlation was found
      between height and head circumference at birth and developmental delay. However,
      the birth weight of children with developmental delay was four times lower than
      that of children with normal development (P = 0.004, odds ratio 4). CONCLUSION:
      Birth weight and male gender were factors that strongly correlated with
      developmental delay in this study.

PMID- 22973116
TI  - Treatment of localized neuropathic pain after disk herniation with 5% lidocaine
      medicated plaster.
AB  - OBJECTIVE: To assess treatment with the 5% lidocaine medicated plaster for
      peripheral neuropathic pain after disk herniation. STUDY DESIGN: Case series,
      single center, retrospective data. PATIENTS AND METHODS: Data of 23 patients
      treated for neuropathic pain with the lidocaine plaster for up to 24 months after
      a protrusion or prolapse of the cervical, thoracic, or lumbar vertebral disks
      were retrospectively analyzed. Changes in overall pain intensity, in intensity of
      different pain qualities and of allodynia and hyperalgesia were evaluated.
      RESULTS: Patients (14 female/nine male, mean age 53.5 +/- 10.4 years) presented
      with radiating pain into the abdomen, back, neck, shoulder, or legs and feet with
      a mean pain intensity of 8.3 +/- 1.5 on the 11-point Likert scale. Mean treatment
      duration was 7.6 months; 52% of the patients received lidocaine plaster as
      monotherapy. At the end of the observation, mean overall pain intensity had been
      reduced to 3.1 +/- 1.8. All other parameters also improved. The treatment was
      well tolerated. CONCLUSION: These results point to a safe and effective treatment
      approach with 5% lidocaine medicated plaster for localized neuropathic pain
      related to disk herniation. However, owing to the small sample size, further
      investigation in a larger-scale controlled trial is warranted.

PMID- 22973117
TI  - Semistructured black-box prediction: proposed approach for asthma admissions in
      London.
AB  - Asthma is a global public health problem and the most common chronic disease
      among children. The factors associated with the condition are diverse, and
      environmental factors appear to be the leading cause of asthma exacerbation and
      its worsening disease burden. However, it remains unknown how changes in the
      environment affect asthma over time, and how temporal or environmental factors
      predict asthma events. The methodologies for forecasting asthma and other similar
      chronic conditions are not comprehensively documented anywhere to account for
      semistructured noncausal forecasting approaches. This paper highlights and
      discusses practical issues associated with asthma and the environment, and
      suggests possible approaches for developing decision-making tools in the form of
      semistructured black-box models, which is relatively new for asthma. Two
      statistical methods which can potentially be used in predictive modeling and
      health forecasting for both anticipated and peak events are suggested.
      Importantly, this paper attempts to bridge the areas of epidemiology,
      environmental medicine and exposure risks, and health services provision. The
      ideas discussed herein will support the development and implementation of early
      warning systems for chronic respiratory conditions in large populations, and
      ultimately lead to better decision-making tools for improving health service
      delivery.

PMID- 22973118
TI  - Polymyalgia rheumatica in a married couple.
AB  - The case of a married couple developing polymyalgia rheumatica (PMR)
      consecutively is presented. The 55-year-old wife complained in June 2010 about
      pain in her neck. Case history, physical examination, and erythrocyte
      sedimentation rate (ESR) of 80 mm/hour led to the diagnosis of PMR. In May 2011,
      her 66-year old husband complained about pain in his neck, shoulders, buttocks,
      and thighs. Considering anamnesis, physical examination, and ESR of 56 mm/hour,
      the diagnosis of PMR was made. Both wife and husband responded to steroid
      treatment. When the steroid dose was gradually reduced, both patients relapsed.
      In order to lower the cumulative dose of glucocorticoid therapy, 10 mg
      methotrexate per week was added. In the literature, six cases of polymyalgia
      rheumatica in married couples have been described to date. In four cases,
      polymyalgia rheumatica occurred first in the wife. The interval of the diagnosis
      between the spouses ranged from 0 to 89 months. Although in most of the previous
      case reports a genetic disposition and an infectious agent have been discussed,
      this hypothesis must be questioned.

PMID- 22973119
TI  - Ferumoxytol: a silver lining in the treatment of anemia of chronic kidney disease
      or another dark cloud?
AB  - Intravenous iron therapy is pivotal in the treatment of anemia of chronic kidney
      disease to optimize the response of hemoglobin to erythropoiesis-stimulating
      agents. Intravenous iron use in patients with chronic kidney disease is on the
      rise. Recent clinical trial data prompting safety concerns regarding the use of
      erythropoiesis-stimulating agents has stimulated new US Food and Drug
      Administration label changes and restrictions for these agents, and has
      encouraged more aggressive use of intravenous iron. The currently available
      intravenous iron products differ with regard to the stability of the iron
      carbohydrate complex and potential to induce hypersensitivity reactions.
      Ferumoxytol is a newer large molecular weight intravenous iron formulation that
      is a colloidal iron oxide nanoparticle suspension coated with polyglucose
      sorbitol carboxymethyl ether. Ferumoxytol has robust iron-carbohydrate complex
      stability with minimal dissociation or appearance of free iron in the serum,
      allowing the drug to be given in relatively large doses with a rapid rate of
      administration. Clinical trials have demonstrated the superior efficacy of
      ferumoxytol versus oral iron with minimal adverse effects. However, recent
      postmarketing data have demonstrated a risk of hypersensitivity that has prompted
      new changes to the product information mandated by the Food and Drug
      Administration. Additionally, the long-term safety of this agent has not been
      evaluated, and its place in the treatment of anemia of chronic kidney disease has
      not been fully elucidated.

PMID- 22973120
TI  - Back to the basics.

PMID- 22973121
TI  - The genetics of schizophrenia.
AB  - Schizophrenia is a complex biological disorder with multifactorial mode of
      transmission where non-genetic determinants are also play important role. It is
      now clear that it involves combined effect of many genes, each conferring a small
      increase in liability to the illness. Thus no causal disease genes or single gene
      of major effects, only susceptible genes are operating. Given this complexity, it
      comes as no surprise of the difficulty to find susceptible genes. However,
      schizophrenia genes have been found at last. Recent studies on molecular genetics
      of schizophrenia which focused on positional and functional candidate genes
      postulated to be associated with schizophrenia are beginning to produce findings
      of great interest. These include neuregulin (NRG-1, 8p12-21), dysbindin,
      (DTNBP1,6p22.3), G72 (13q34) / D-amino acid oxidase (DAAO,12q24), proline
      dehydrogenase (PRODH-2, 22q11.21), catechol-O-methyltransferase (COMT, 22q11.21),
      regulator of G protein signaling (RGS-4), 5HT2A and dopamine D3 receptor (DRD3).
      Applications of microarrays methods were able to locate positional candidate
      genes related to dopaminergic, serotonergic and glutamatergic neurotransmission.
      New genome scan project, seen in the light of previous scans, provide support for
      schizophrenia candidate region on chromosome 1q, 2q, 5q, 6p, 8p, 10p, 13q,15q and
      22q. Other reports described including the application of LD mapping and
      positional cloning technique, microarray technology and efforts to develop
      quantitative phenotype. More exciting finding is expected in near future with the
      completion of Hap Map project.

PMID- 22973122
TI  - Effects of very low blood lead levels on neurobehavioral performances of male
      policemen in kota bharu, kelantan.
AB  - Many published studies that examined the effect of lead exposure on
      neurobehavioral performances were conducted in confined manufacturing environment
      with low to moderate blood lead levels as a marker of exposure. This study was
      conducted in a general environmental setting with very low exposure intensity and
      blood lead levels. The objective of the study was to determine the effect of very
      low blood lead levels (below 10 MUg/dl) on the neurobehavioral performances of
      policemen in Kota Bharu, Kelantan. The study, conducted between August 25(th) and
      October 20(th) 2001, was cross-sectional in design and comprised of 89 policemen
      working in Kota Bharu district. The lead concentration of venous blood was
      determined using graphite furnace absorption spectrometer. We assessed
      neurobehavioral performances using the WHO Neurobehavioral Core Test Battery
      (NCTB). The mean blood lead concentration was 2.5 + 1.0 mg/dl. Among the seven
      tests performed, the positive effect of blood lead on Benton visual retention was
      not significant after controlling for the confounding effect of smoke-dose. This
      study suggested that very low blood lead levels have no significant effects on
      the neurobehavioral performances. Therefore, more studies with blood lead levels
      below the recommended environmental limit of 10 mg/dl, as recommended by Centers
      for Disease Control (CDC), be conducted in order to justify that limit.

PMID- 22973123
TI  - Analysis of the Psychometric Properties of the Malay Version of Beck Depression
      Inventory II (BDI-II) Among Postpartum Women in Kedah, North West of Peninsular
      Malaysia.
AB  - Increased international collaboration in clinical trials has created a need for
      cross culturally valid instruments to assess the quality of life and behavioural
      disorders. Cross cultural studies of depressive symptomatology, in particular,
      must be preceded by an exhaustive study of the psychometric properties of the
      instruments to ensure the validity of the comparison. In this article, we
      examined the validity, reliability and factor structure of the Malay version of
      the Beck Depression Inventory II (BDI-II) among Malay postpartum women attending
      selected health centres in Kedah, North West of Peninsular Malaysia. Our findings
      indicated that the current version of the BDI-II is psychometrically strong and
      appropriate for use in assessing depressive symptomatology among this group of
      women.

PMID- 22973124
TI  - Psychometric Evaluation of the Medical Outcome Study (MOS) Social Support Survey
      Among Malay Postpartum Women in Kedah, North West of Peninsular Malaysia.
AB  - The Malay version of the Medical Outcome Study (MOS) Social Support Survey was
      validated among a sample of postpartum Malay women attending selected health
      centers in Kedah, North West of Peninsular Malaysia. 215 women between 4 to 12
      weeks postpartum were recruited for the validation study. They were given
      questionnaires on socio-demography, the Malay-versions of the MOS Social Support
      Survey, Edinburgh Postnatal Depression Scale (EPDS) and the 21-items Beck
      Depression Inventory-II (BDI-II). 30 of the women, who were bilingual, were also
      given the original English version of the instrument. A week later, these women
      were again given the Malay version of the MOS Social Support Survey. The scale
      displayed good internal consistency (Cronbach's alpha = 0.93), parallel form
      reliability (0.98) and test-retest reliability (0.97) (Spearman's rho; p<0.01).
      The negative correlations of the overall support index (total social support
      measure) with the Malay versions of EPDS and BDI-II confirmed its validity.
      Extraction method of the 19 items (item 2 to item 20) from the MOS Social Support
      Survey using principle axis factoring with direct oblimin rotation converged into
      3 dimensions of functional social support (informational, affectionate / positive
      social interaction and instrumental support) with reliability coefficients of
      0.91, 0.83 and 0.75 respectively. The overall support index also displayed low
      but significant correlations with item 1 which represents a single measure of
      structural social support in the instrument (p <0.01). The Malay version of the
      MOS Social Support Survey demonstrated good psychometric properties in measuring
      social support among a sample of Malay postpartum Malay women attending selected
      health centers in Kedah, North West of Peninsular Malaysia and it could be used
      as a simple instrument in primary care settings.

PMID- 22973125
TI  - Reliability and validity of the respiratory score in the assessment of acute
      bronchiolitis.
AB  - Children with bronchiolitis from Hospitals Universiti Sains Malaysia (HUSM) and
      Hospital Kota Bharu (HKB) were student using the Kristjansson Respiratory Score
      and the Wang Respiratory Score respectively. Saturation of oxygen (S(a)O(2)) was
      measured with a pulse-oximeter while the child is breathing room-air. Two
      observers assessed the respiratory scores in all children independently. The
      correlation between respiratory scores and S(a)O(2) was assessed using Spearman's
      Rho, and the inter-rater reliability of respiratory scores determined using
      intraclasscorelation coefficient. There were 29 children in HUSM and 25 from HKB
      with a median age of 8 months (IQR 4.5 months) and 9 months(IQR 7 months)
      respectively. In HUSM, the median Kristjansson Respiratory Score for both
      observers was 4 (IQR 2), and the median S(a)O(2) was 96% (IQR 3%). The
      correlation coefficient between the Kristjansson Respiratory Score and S(a)O(2)
      for the first observer was - 0.75 (p <0.001), and for the second observer -0.73
      (p <0.001). In HKB, the median Wang Respiratory Score was also similar for both
      observers (median 4 IQR 4.5), and the median (IQR) for S(a)O(2) was 96% (2%). The
      correlation coefficient between the Wang Respiratory Score and S(a)O(2) for the
      first observer was -0.41 (p = 0.04) and for the second observer -0.43 (p = 0.03).
      The inter-rater reliability between the first and second observer was high for
      both the Kristjansson Respiratory (ICC 0.89) and the Wang Respiratory Scores (ICC
      0.99). In conclusion the validity of the Kristjansson Respiratory Score was high
      whereas the validity of the Wang Respiratory Score was moderate in the assessment
      of the severity of acute bronchiolitis. Both respiratory scores and physical
      signs showed high agreement between observers. The Kristjansson Respiratory Score
      should be considered for use by medical personnel in the assessment of the
      severity of acute bronchiolitis in children.

PMID- 22973126
TI  - Dental anomalies and facial profile abnormality of the non-syndromic cleft lip
      and palate children in kelantan.
AB  - This study was done to determine the prevalence of dental anomalies and facial
      profile abnormality and its association with the non-syndromic cleft lip and
      palate (CLP) as compared to the non-cleft children. A comparative cross sectional
      study was conducted where the case group consist of 98 non-syndromic CLP children
      unilateral (UCLP) and bilateral (BCLP) who attended the Combined Clinic at Kota
      Bharu Dental Clinic (KBDC) while the comparison group comprised of 109 non-cleft
      children who attended the outpatient clinic at KBDC. Their ages were between 3 to
      12 years old. Clinical oral and facial profile examinations were carried out to
      look for dental anomalies (morphology, number and alignment of teeth) and facial
      profile abnormality. The prevalence of anomalies in morphology of teeth in CLP
      (24.5%) and non-cleft (10.1%), number of teeth in CLP (44.9%) and non-cleft
      (7.3%), mal-alignment in CLP (79.6%) and non-cleft (27.5%) and facial profile
      abnormality in CLP (26.5%) and non-cleft (9.1 %). There was a significant
      association between CLP and anomalies in morphology, number, mal-alignment and
      abnormality in facial profile; (p < 0.05). Therefore, there was a high prevalence
      and risk of dental anomalies and facial profile abnormality in the CLP children
      compared to the non-cleft children.

PMID- 22973127
TI  - Medication errors among geriatrics at the outpatient pharmacy in a teaching
      hospital in kelantan.
AB  - The main aim of this study was to determine the medication errors among
      geriatrics at the outpatient pharmacy in a teaching hospital in Kelantan and the
      strategies to minimize the prevalence. A retrospective study was conducted that
      involved screening of prescription for a one-month period (March 2001). Only
      15.35% (1601 prescription) of a total 10,429 prescriptions were for geriatrics.
      The prescriptions that were found to have medication errors was 403. Therefore,
      the prevalence of medication errors per day was approximately 20 cases.
      Generally, the errors between both genders were found to be comparable and to be
      the highest for Malays and at the age of 60-64 years old. Administrative errors
      was recorded to be the highest which included patient's particulars and validity
      of the prescriptions (70.22%) and drugs that available in HUSM (16.13%). Whereas
      the total of prescribing errors were low. Under prescribing errors were
      pharmaceutical error (0.99%) and clinical error (8.68%). Sixteen cases or 3.98%
      had more than 1 error. The highest prevalence went to geriatrics who received
      more than nine drugs (32.16%), geriatrics with more than 3 clinical diagnosis
      (10.06%), geriatrics who visited specialist clinics (37.52%) and treated by the
      specialists (31.07%). The estimated cost for the 403 medication errors in March
      was RM9,327 or RM301 per day that included the cost of drugs and humanistic cost.
      The projected cost of medication errors per year was RM 111,924. In conclusion,
      it is very clear that the role of pharmacist is very great in preventing and
      minimizing the medication errors beside the needs of correct prescription writing
      and other strategies by all of the heath care components.

PMID- 22973128
TI  - A descriptive analysis of exercise tolerance test at seremban hospital : an audit
      for the year 2001.
AB  - Our purpose is to report on the epidemiological variables and their association
      with the results of the exercise tolerance test (ETT) in the series of patients
      referred for standard diagnostic ETT at Seremban Hospital during the year 2001.
      ETT is widely performed, but, in Malaysia, an analysis of the associations
      between the epidemiological data and the results of the ETT has not been
      presented. All patients referred for ETT at Seremban Hospital who underwent
      exercise treadmill tests for the year 2001 were taken as the study population.
      Demographic details and patients with established heart disease (i.e. prior
      coronary bypass surgery, myocardial infarction, or congestive heart failure) were
      noted. Clinical and ETT variables were collected retrospectively from the
      hospital records. Testing and data management were performed in a standardized
      fashion with a computer-assisted protocol. This study showed that there was no
      significant predictive epidemiological variable on the results of the ETT.
      However, it was found that there was statistically significant difference between
      the peak exercise time of males and females undergoing the ETT.

PMID- 22973130
TI  - School of medical sciences, universiti sains malaysia - the first 25 years in
      poetry.

PMID- 22973129
TI  - Hoarseness of Voice in a Patient with Mitral Stenosis and Ortner's Syndrome.
AB  - Rheumatic mitral stenosis is prevalent in this part of the world and it gives
      rise to wide array of manifestations. However, hoarseness of voice secondary to
      recurrent laryngeal nerve paralysis (Ortner's syndrome) is an uncommon
      manifestation. This case illustrates an uncommon presentation in a common
      disease. A 29-year-old lady presented with a 2-year history of hoarseness of
      voice. Physical examination revealed a mid-diastolic murmur and left vocal cord
      paralysis. Echocardiography confirmed mitral stenosis with pulmonary
      hypertension. She underwent percutaneous mitral balloon valvotomy in 1991 with
      return of normal speech after a few months. The recurrent laryngeal nerve
      paralysis is mainly due to the compression by an enlarged pulmonary artery as
      initially thought. This complication is rarely seen nowadays due to greater
      awareness of the disease and earlier intervention. With the advent of
      percutaneous transvenous mitral valvotomy in the nineties, effective non-surgical
      intervention is plausible.

PMID- 22973131
TI  - Poor perception of subjective change in breathlessness- a randomized, crossover,
      placebo-controlled study of asthmatic subjects.

PMID- 22973132
TI  - The Malaysian Journal of Medical Sciences in its 18th Year: a look at the
      journal's growth.
AB  - As a small-although growing-journal based in Malaysia, the Malaysian Journal of
      Medical Sciences (MJMS) has faced several challenges in the past, such as
      promoting our journal as well as making sure our article bank does not go empty.
      However, we strive to improve ourselves by taking all means necessary to increase
      the quantity and, most importantly, quality of our publications, as well as to
      increase our journal's visibility and citability. This editorial will focus on
      MJMS statistics throughout 2011-where MJMS turned 18-as well as future plans for
      our journal.

PMID- 22973134
TI  - Comparison of job satisfaction among eight health care professions in private
      (non-government) settings.
AB  - BACKGROUND: A comparison of the job satisfaction of health care professionals has
      not been well studied in Malaysia. This study aimed to compare the job
      satisfaction level among 8 groups of health care professionals in private
      settings, using the Job Satisfaction Survey (JSS). METHODS: A total of 81 health
      care professionals, including nurses, physiotherapists, occupational therapists,
      medical laboratory technologists, dieticians, medical imaging practitioners,
      environmental health officers, and optometrists in private (non-government)
      settings in the Klang Valley, were interviewed using the Job Satisfaction Survey
      scale invented by Dr Paul E Spector. Their job satisfaction scores were
      calculated and determined. RESULTS: In the demographic data, the majority of the
      subjects were 20-30 years old (81.5%), were female (72.8%), had a basic degree
      (98.8%), were single (64.2%), and had 1-5 years of working experience (83.9%). A
      Kruskal-Wallis analysis showed significant differences (P < 0.05) in promotion,
      supervision, operating conditions, co-workers, nature of the work, and
      communication, but there were no significant differences (P > 0.05) in pay,
      fringe benefits, and contingent rewards in JSS score among the 8 health care
      professions. The Friedman Test showed a significant difference of overall JSS
      scores (chi(2) = 526.418, P < 0.001) among the 8 health care professions.
      CONCLUSION: The overall job satisfaction levels are different among health care
      professionals in private settings, especially regarding promotion, supervision,
      operating conditions, co-workers, the nature of the work, and communication.

PMID- 22973135
TI  - The prevalence of cardiovascular risk factors in the young and middle-aged rural
      population in Sarawak, Malaysia.
AB  - BACKGROUND: Coronary heart disease (CHD) was the second leading cause of death in
      Malaysia in 2006. CHD has known risk factors including hypertension, diabetes
      mellitus, and obesity. METHODS: This cross-sectional study examined the
      prevalence of cardiovascular risk factors among 260 participants aged 20 to 65
      years in a rural community in Sarawak. RESULTS: The prevalences of overweight and
      obesity in this study were 39.6% and 11.9%, respectively. Approximately 13% of
      participants had hypertension, and 1.5% had a random blood sugar greater than
      11.1 mmol/L. Chi-square tests showed significant associations between obesity and
      gender (P = 0.007), low high-density lipoprotein cholesterol and race (P = 0.05),
      high total cholesterol and age (P = 0.007), age and hypertension (P = 0.011),
      smoking and gender (P < 0.001), and smoking and income (P = 0.050). Age-adjusted
      logistic regression showed that women were 0.246 times more likely to be obese,
      that older participants (> 45 years) were 0.395 times more likely to have high
      cholesterol and that those with a higher monthly household income (> RM830) were
      2.471 times more likely to smoke. CONCLUSION: These findings indicate that we
      should be concerned about the high rates of overweight in this rural community to
      prevent obesity.

PMID- 22973133
TI  - Cytoadherence and severe malaria.
AB  - Malaria is a disease that causes enormous human morbidity and mortality. One
      feature of mature Plasmodium falciparum-infected erythrocytes leading to the
      development of severe malaria is thought to be cytoadherence and blockage of the
      microvasculature. Therefore, an understanding of mechanisms that mediate parasite
      adhesion leading to malaria pathology is needed to yield new treatments for
      malaria. However, to date, cytoadherence-associated pathology is still under
      debate. Is cytoadherence needed to develop severe malaria? This review will
      discuss the available information on associations of cytoadherence with the
      development of severe malaria.

PMID- 22973136
TI  - Perceived effects of the Malaysian National Tobacco Control Programme on
      adolescent smoking cessation: a qualitative study.
AB  - BACKGROUND: The prevalence of teenage smoking has decreased over the past decade
      following the implementation of the national tobacco control programme. However,
      the effect of the programme on smoking cessation in teenagers has not been
      determined. METHODS: Twenty-eight participants (12 teenagers, 8 teachers, and 8
      doctors) were interviewed using 5 in-depth interviews and 3 group discussions.
      Social cognitive theory (SCT) was applied as the theoretical framework. Semi
      structured interview protocols were used, and thematic analysis and analytic
      generalisation utilising SCT were performed. RESULTS: The current national
      tobacco control programme was found to be ineffective in promoting smoking
      cessation among teenagers. The participants attributed the ineffective campaign
      to the followings: inadequacy of message content, lack of exposure to the
      programme, and poor presentation and execution. In addition, the participants
      perceived the developed tobacco control policies to be a failure based on poor
      law enforcement, failure of retailers to comply with the law, social availability
      of cigarettes to teenagers, and easy availability of cheap, smuggled cigarettes.
      This study highlighted that the programme-related problems (environmental
      factors) were not the only factors contributing to its perceived ineffectiveness.
      The cunning behaviour of the teenagers (personal factor) and poor self-efficacy
      to overcome nicotine addiction (behavioural factor) were also found to hinder
      cessation. CONCLUSION: Tobacco control programmes should include strategies
      beyond educating teenagers about smoking and restricting their access to
      cigarettes. Strategies to manage the cunning behaviour of teenagers and
      strategies to improve their self-efficacy should also be implemented. These
      comprehensive programmes should have a foundation in SCT, as this theory
      demonstrates the complex interactions among the environmental, personal, and
      behavioural factors that influence teenage smoking.

PMID- 22973137
TI  - Comparison of refractive error and visual impairment between Native Iban and
      Malay in a formal government school vision loss prevention programme.
AB  - BACKGROUND: The epidemiological study of vision problems is important for
      developing national strategies for the prevention of visual impairment. There was
      a lack of information regarding vision problems among school children in East
      Malaysia. The purpose of this study was to compare the refractive errors and
      degrees of visual impairment between Native Iban and Malay school children who
      participated in a formal government vision loss prevention programme conducted in
      a rural area of Betong Division, Malaysia. METHODS: In total, 293 Native Iban and
      Malay school children (Standard 1, Standard 6, and Form 3) received refractive
      assessments by an optometrist after failing tests in the formal government school
      vision screening programme in 2008. A criterion for referral was a visual acuity
      of 6/9 or worse in either eye. Assessments of the refractive errors of the
      children were performed using dry retinoscopy and subjective refraction
      techniques at community clinics. RESULTS: The overall prevalences of refractive
      error and visual impairment among the sampled populations were 47.7% and 3.5%,
      respectively. Approximately 97.1% of reported cases were myopia. The Malay sample
      population was found to be more myopic than the Native Iban population (U =
      8240.50, P < 0.05, r = 0.14), but no significant association was found between
      myopia and ethnicity (chi(2) = 2.66, P > 0.05). Both Native Iban and Malay
      children in education levels higher than Standard 1 were more likely to have
      myopia (P < 0.05). Myopia was found to be more likely to affect females than
      males at a statistically significant level among Native Iban children (chi(2)
      [1.N = 170] = 6.279, P < 0.05, odds ratio = 2.327, 95% CI = 1.184-4.575). There
      was no statistically significant association between visual impairment and
      ethnicity (chi(2) = 1.60, P > 0.05). Approximately 94.1% of children with
      refractive errors suffered from having either the wrong prescription (7.8%) or
      having uncorrected refractive errors (92.2%). CONCLUSION: The Native Iban
      population was found to be less myopic than the Malay population despite having a
      similar frequency of myopia. The proportion of children with myopia increased
      with the level of education in both ethnicities. A high percentage of untreated
      refractive error problems among Native Iban and Malay children in the Betong
      Division indicates that there is a need for government intervention for the
      purpose of economic and healthcare improvements.

PMID- 22973138
TI  - Relationship between food habits and tooth erosion occurrence in Malaysian
      University students.
AB  - BACKGROUND: Tooth erosion is a growing dental problem; however, the role of diet
      in the aetiology of tooth erosion is unclear. A cross-sectional study was
      conducted to determine the association between tooth erosion occurrence and the
      consumption of acidic foods and drinks among undergraduate university students.
      METHODS: A total of 150 undergraduate students (33 males and 117 females) aged 19
      to 24 years at Universiti Kebangsaan Malaysia participated in this study. The
      Basic Erosive Wear Examination was used to assess the occurrence of tooth
      erosion. Information regarding dental hygiene practices, usual dietary habits,
      and consumption of acidic foods and drinks was obtained through a structured
      questionnaire. RESULTS: In all, 68% of subjects had tooth erosion. Subjects who
      reported having received information about healthy eating were less likely to
      have tooth erosion (chi(2) [1, N = 150] = 7.328, P = 0.007). The frequencies of
      milk (OR = 0.29, 95% CI = 0.13-0.67) and tea/coffee (adjusted OR = 0.42, 95% CI =
      0.19-0.95) consumption were negatively associated with tooth erosion. Dental
      hygiene practice, the frequency and amount of acidic food and drink intake, and
      body mass index classification were not significantly associated with the risk of
      tooth erosion (P > 0.05). CONCLUSION: A high prevalence of tooth erosion was
      observed among this group of students. Preventive measures, such as dietary
      advice and increased consumption of milk at a younger age, may reduce the
      occurrence of tooth erosion among this age group.

PMID- 22973139
TI  - Acute meningoencephalitis in hospitalised children in southern Bangladesh.
AB  - BACKGROUND: Acute meningoencephalitis is an important cause of morbidity and
      mortality around the globe. The objective of this study was to examine the
      distribution of acute meningoencephalitis and its aetiological agents among
      children admitted to a tertiary hospital in southern Bangladesh. METHODS: This
      prospective study was carried out in Khulna Medical College Hospital from 2007 to
      2009. All of the admitted children between 1 month and 12 years of age were
      enrolled over a 2-year period if they met the inclusion criteria of having an
      acute onset of fever (<= 14 days) and any of the following 3 signs: neck
      stiffness, convulsion, or altered mental status. Cerebrospinal fluid (CSF) was
      collected within hours and sent to the laboratory for cytological and biochemical
      analyses. CSF was examined by Gram staining and a latex agglutination test to
      detect common bacteria. Serum and CSF were also tested for Japanese encephalitis
      virus antibodies. RESULTS: A total of 140 children were included in the study,
      which accounted for 2.5% of admissions between 2007 and 2009. The number of acute
      meningoencephalitis cases was relatively higher (37.9%) during the monsoon
      season. The CSF report revealed a pyogenic form in 24 (18.5%) and a viral form in
      13 (10.0%) cases. Altered mental status was significantly less frequent (P <
      0.001) in cases of pyogenic meningoencephalitis (62.5%) than in cases of non
      pyogenic meningoencephalitis (93.4%). Bacterial causes were identified in 11
      (8.5%) children; the causative agents included Streptococcus pneumoniae (n = 8),
      Neisseria meningitides (n = 2), and Haemophilus influenzae (n = 1). Three (2.3%)
      patients were positive for Japanese encephalitis virus. CONCLUSION: S. pneumoniae
      was the most common bacteria causing acute meningoencephalitis among the study
      subjects, and Japanese encephalitis virus was present in few patients.

PMID- 22973140
TI  - Financial loss and suicide.
AB  - The current Western psychiatric wisdom states that suicide is always or almost
      always associated with mental disorder. Careful Asian studies are casting doubt
      on this conclusion. Using information from the public record (newspapers,
      coroner's reports, and various web-based sources), we sought evidence that, in
      the absence of mental disorder, suicide may be associated with major financial
      loss. Reports of 15 individuals who completed suicide following major financial
      loss were identified, thus an association between these events is supported.

PMID- 22973141
TI  - Isolated blunt lingual artery injury secondary to a road traffic accident:
      diagnostic and therapeutic approach.
AB  - Neurologic and airway compromise as a result of traumatic vascular injuries to
      the neck region often lead to more severe complications and thus require special
      consideration. Furthermore, these cases pose diagnostic and therapeutic
      challenges to healthcare providers. Here, we report a case of a 28-year-old
      motorcyclist presenting with progressively enlarged Zone 2 neck swelling on the
      left side following a high impact collision. There were no symptoms or signs
      suggesting neurologic or laryngeal injury. Computed tomography angiogram of the
      neck revealed signs of an active arterial bleed. The apparent vascular injury was
      managed by close observation for signs of airway compromise, urgent angiogram,
      and selective catheter embolisation of the left lingual artery. The patient
      subsequently recovered without further operative exploration of the neck. At 6
      months post-trauma, the neck swelling fully subsided with no complications from
      angioembolisation. This case illustrates the individualised treatment and
      multidisciplinary approach in managing such cases. We review our rationale for
      this diagnostic and therapeutic approach.

PMID- 22973142
TI  - Breast carcinoma occurring from chronic granulomatous mastitis.
AB  - Chronic granulomatous mastitis is known as a benign and relatively rare disorder
      that is often difficult to differentiate from breast carcinoma. We highlight the
      case of a 34-year-old woman who had recurrent episodes of right breast swelling
      and abscess for 8 years. These were proven to be chronic granulomatous mastitis
      by tissue biopsies on 3 different occasions. Her condition improved on similar
      courses of antibiotics and high-dose prednisolone. However, she subsequently
      developed progressive loss of vision due to an orbital tumour. She then underwent
      a craniotomy and left orbital decompression with excision of the tumour, which
      proved to be a metastatic carcinoma. A trucut biopsy of the right breast was then
      done and showed features consistent with an infiltrating ductal carcinoma. This
      case illustrates the possibility that chronic granulomatous mastitis could be a
      precursor for malignancy and the difficulty in differentiating one from the
      other. The possible mechanisms of development and the implications for future
      management are also discussed.

PMID- 22973143
TI  - Pheochromocytoma: an uncommon presentation of an asymptomatic and biochemically
      silent adrenal incidentaloma.
AB  - Pheochromocytomas are rare tumours originating from the chromaffin tissue. The
      clinical manifestations are variable and are not specific; as a result,
      pheochromocytomas often imitate other diseases. The diagnosis is usually
      established by biochemical studies, i.e., the measurement of catecholamines or
      their metabolites in urine or plasma, followed by radiographic and scintigraphic
      studies for localisation. Surgical removal of the tumour is the preferred
      treatment. We report a 30-year-old woman presenting with an adrenal incidentaloma
      that was 7.6 * 5.3 * 4.8 cm in size on an abdominal computed tomography scan.
      Investigations for adrenal hormones, including a low-dose dexamethasone
      suppression test, plasma aldosterone level, 24-hour urinary metanephrine and
      vanillylmandelic acid levels, and plasma metanephrine level were all within the
      normal ranges. During the surgical resection, the patient had a hypertensive
      spell. Surgery was postponed, and the blood pressure was adequately controlled
      with alpha blockers, followed by beta blockers. After 2 weeks, the surgery was
      followed by a pathological biopsy that confirmed the pheochromocytoma diagnosis.

PMID- 22973144
TI  - Acute lower gastrointestinal haemorrhage secondary to small bowel ascariasis.
AB  - Acute lower gastrointestinal haemorrhage secondary to small bowel ascariasis is
      extremely rare. A high level of suspicion should be maintained when dealing with
      acute gastrointestinal haemorrhage in migrants and travellers. Small bowel
      examination is warranted when carefully repeated upper and lower endoscopies have
      failed to elicit the source of bleeding. Appropriate test selection is determined
      by the availability of local expertise. We present a case of acute lower
      gastrointestinal haemorrhage secondary to jejunal ascariasis and a literature
      search on lower gastrointestinal haemorrhage associated with jejunal infestation
      with Ascaris.

PMID- 22973145
TI  - Letter to the editor: a new start with fMRI.

PMID- 22973146
TI  - Letter to the editor: Comparative cognitive neuroscience: non-human primate study
      in the understanding of human appreciation of colours.

PMID- 22973147
TI  - Letter to the editor: Introducing physician assistants to Thailand's rural
      health.

PMID- 22973148
TI  - Letter to the editor: Syphilis seroreactivity: determining the importance during
      routine screening.

PMID- 22973149
TI  - Gender difference in safe and unsafe practice of pesticide handling in tobacco
      farmers of malaysia.
AB  - To identify gender difference in safe and unsafe practice of pesticide handling
      in tobacco farmers of Malaysia, we conducted a 20-item questionnaire interview on
      storage of pesticide (4 questions), mixing of pesticide (3 questions), use of
      personal protective equipment and clothing while spraying pesticide (7
      questions), activities during and after spraying of pesticide (5 questions), and
      maintenance of pesticide sprayer (1 question) in 496 tobacco farmers (395 males
      and 101 females) in Bachok District, Kelantan, Malaysia. Duration of employment
      was significantly longer in females than those in males (p<0.001). In addition,
      proportion with no formal education in females was significantly higher than
      those in males (p<0.05). The following eight common factors were extracted from
      the 20 questionnaires by principal components factor analysis after varimax
      rotation in all farmers: (1) use of personal protective equipment, (2) unsafe
      work habit, (3) reading and following instructions on pesticide label, (4)
      security, storage and disposal of pesticide container, (5) safe work habit, (6)
      proper handling of pesticide and maintenance of pesticide sprayer, (7) use of
      personal protective clothing, and (8) safe handling of pesticide. Results of
      analysis of covariance for the eight factor scores of all male and female
      farmers, controlling for educational level and duration of employment, showed
      that: (1) factor scores for use of personal protective equipment (p<0.001), use
      of personal protective clothing (p<0.001) and safe work habit (p<0.001) in
      females were significantly lower than those in males; (2) conversely, factor
      scores for reading and following instruction on pesticide label (p<0.001) and
      proper handling of pesticide and maintenance of pesticide sprayer (p<0.01) in
      males were significantly lower than those in females; and (3) there were no
      significant differences in other three factor scores (p>0.05). We therefore
      conclude that: (1) for female tobacco farmers, choice of personal attire tend to
      result in lower scores on use of personal protective equipment and personal
      protective clothing while personal hygiene practices result in lower score on
      safe work habit; and, (2) for male tobacco farmers, the lower scores on reading
      and following instruction on pesticide label and mixing pesticide and maintenance
      of pesticide sprayer in good condition suggests that they were not primarily
      involved in these activities. It is postulated that these differences in safe and
      unsafe practices of pesticide handling across gender is related to the choice of
      personal attire, personal hygiene practices and division of labour within farming
      households which in turn is influenced by prevailing sociocultural norms in the
      community.

PMID- 22973150
TI  - An approach to the patient with osteoporosis.
AB  - Osteoporosis is recognised as a public health problem the world over. There is
      increasing awareness about this problem in Malaysia and this is particularly
      important, as our population gets older. This brief review aims to highlight the
      important aspects of history taking as well as the investigative approach to the
      diagnosis of osteoporosis. The modalities of bone mineral density measurements
      particularly with regards to the diagnosis and the monitoring of the disease are
      also discussed.

PMID- 22973151
TI  - Adolescent's Attitudes Towards Health Warning Message on Cigarette Packs.
AB  - A total of 190 secondary four male school students from three schools in Kota
      Bharu were surveyed on their smoking habits and their attitudes towards the
      health warning messages on cigarette packs. There were 57 (30.0%) students who
      were current smokers, 45 (23.7%) students who were ex-smokers and 88 (46.3%)
      students who have never smoked cigarettes. Nearly all current and ex-smokers
      (95.1%) as well as non-smokers (94.3%) knew the wording of the health warning
      message currently displayed on cigarette packs. Almost all the students (95.3%)
      also knew where the warning message was placed. There were more ex-smokers and
      non-smokers (70.5%) compared to current smokers (50.0%) who felt that there
      should be different health warning messages and each should be displayed
      concurrently on different cigarette packs. The students felt that the current
      health message was not effective to motivate smokers to quit (score=2.25).
      Alternative messages which the students felt may be more effective were 'Smoking
      is dangerous for pregnancy' (score = 3.3), 'Cigarette smoke is dangerous for your
      child' (score=3.11) and 'Smoking can kill you' (score=3.08). The current health
      message "Smoking is dangerous for your health' is eighth with a score of only
      2.64. The students felt that the least effective message was 'Cigarettes are
      drugs' (score=2.22). Most of the students (80.0%) felt that the health warning
      message should be placed at the front instead of on the side of the cigarette
      pack to be more effective.

PMID- 22973152
TI  - Observational study on cannulation rate during ERCP at hospital alor setar.
AB  - ERCP (Endoscopic Retrograde Cholangiopancreaticography) was introduced in this
      hospital in late 1995. Since then, a lot of improvement have been achieved in the
      management of biliary tract diseases. Various general surgeons posted to this
      hospital have been trained in this procedure. A study was done to include all
      patients admitted for ERCP from August 1998 to July 1999. A total of 322 new
      patients with a mean of 26.9 cases a month had underwent this procedure. The
      duration of cannulation varied from 2 minutes to 45 minutes with a mean of 12
      minutes. Cannulation rate by various surgeons differed. Overall success rate was
      80%. Mortality was 0.6 % and morbidity was 0.9%. ERCP is safe and it takes at
      least 6 months of regular duodenoscopy before one can master the technique.
      Achieving 80% cannulation rate, has definitely reduced unnecessary common bile
      duct (CBD) explorations. During this study we have trained various surgeons in
      this procedure and at least 2 surgeons could be credentialled according to the
      guidelines provided by the Malaysian Society of Gastroenterology and Hepatology.
      During this study we have identified various reasons for the failure of
      cannulation which are useful for future training of endoscopists.

PMID- 22973153
TI  - Preliminary study suggests low incidence of gastric carcinoma in kelantan relates
      to low rate of helicobacter pylori infection.
AB  - Helicobacter pylori-associated gastric carcinoma is generally more common in the
      antrum/body and is of the intestinal type. The aim of this study was to determine
      the pattern of gastric carcinoma in an area known to have a low prevalence of H.
      pylori. Pathology records of gastric carcinoma diagnosed at Hospital University
      Sains Malaysia between 1995 and 1999 were retrieved and studied. There were a
      total of 23 cases. The median age was 60 years. Eighteen patients were Malay and
      5 were Chinese. The most common location of the tumour was the
      cardia/gastrooesophageal junction (61%, 14/23 patients). The majority was of the
      intestinal type (69.6%, 16/23). The frequency of gastric carcinoma appears to be
      exceptionally low in the area of study. The Chinese population was over
      represented. The higher frequency of tumour in the cardia/gastro-oesophageal
      junction as compared to the antrum and body is in sharp contrast to most other
      studies. This reaffirms the notion that Helicobacter pylori infection is a
      causative agent for non-cardia gastric carcinomas.

PMID- 22973154
TI  - Pulmonary Tuberculosis in HIV Infection : The Relationship of the Radiographic
      Appearance to CD4 T-Lymphocytes Count.
AB  - Pulmonary tuberculosis (TB) in the AIDS population has a variable chest
      radiographic presentation. The association between the chest radiographic
      presentation of pulmonary TB and CD4 T-lymphocyte count in the HIV-infected
      patient was investigated in order to provide an empirical approach for early
      diagnosis, treatment, and isolation of these patients. A retrospective analysis
      of chest radiographs, CD4 T-lymphocyte counts, and clinical history of 80
      patients from Hospital Kota Bharu, was performed. All patients were HIV
      seropositive and had culture and /or cytology-proven pulmonary tuberculosis.
      Radiographs were evaluated for the presence of atypical or typical patterns of
      pulmonary TB. Thirteen (16.2%) patients had typical postprimary pattern, where
      opacities were distributed at the upper zones, with or without cavitation. Sixty
      seven (83.8%) patients had atypical patterns, consisting of normal chest
      radiograph, middle and/or lower zones parenchymal opacities, mediastinal
      lymphadenopathy, pleural effusion and miliary TB. Of these, 18 (22.5%) patients
      demonstrated normal chest radiographs, 36 (45%) patients showed parenchymal
      opacities at the middle and/or lower zones of the lungs, 30 (37.5%) had
      mediastinal lymphadenopathy, 18 (22.5%) revealed pleural effusion and 6 (7.5%)
      presented with miliary TB. Sixty-two (77.5%) patients had CD4 T-lymphocytes count
      less than 200 cells/ul. Of these patients, only 1 (1.6%) had typical pattern.
      Eighteen (22.5%) patients had CD4 T-lymphocyte count more than 200 cells/ul,
      where 12 (66.7%) of them showed typical pattern. Patients with CD4 T-lymphocytes
      count of less than 200 cells/ul, were more likely to produce normal chest
      radiographs, middle and /or lower zones parenchymal opacities and mediastinal
      lymphadenopathy. The mean CD4 T-lymphocytes count were also found significantly
      lower. AIDS patients with pulmonary TB can present with both typical and atypical
      chest radiograph patterns. An AIDS patient who had CD4 T-lymphocytes count less
      than 200 cells/ul were more likely to present with atypical radiographic
      appearance of pulmonary TB. They required appropriate treatment and isolation
      until the diagnosis of pulmonary TB was confirmed.

PMID- 22973155
TI  - Comparison between the Effect of Soybean and Goat's Milk on Tumor-Marker Enzyme
      Activities During Hepatocarcinogenesis in Rats.
AB  - Milk is a physiological fluid which has high nutritional value and soybean has
      strong antioxidant characteristics which is believed to inhibit carcinogenesis.
      The objective of this study was to investigate the effects of administration of
      soybean and goat's milk on hepatocarcinogenesis in rats (fed with
      diethylnitrosamine; DEN and acetylaminofluorene; AAF) by determining the
      activities of plasma gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase
      (ALP). Thirty-six rats from the species Sprague-Dawley were divided into 6 groups
      : control, DEN/AAF, soybean, DEN/AAF with soybean treatment, goat's milk and
      DEN/AAF with goat's milk treatment. Soybean and goat's milk administrations were
      given 5 ml/day. The rats were sacrificed after 8 weeks and the blood was
      collected. Treatment with DEN/AAF caused an increase in ALP and GGT levels and a
      decrease in weight significantly (p<0.05). ALP and GGT activities decreased
      significantly after administration of soybean and goat's milk (p<0.05).
      Administration of goat's milk and soybean alone did not cause any changes in the
      enzyme activities. Comparison between the effect of soybean and goat's milk in
      reducing the enzyme activities (ALP and GGT) did not give significant values
      (p>0.05). However, a decrease in weight was observed in the rats given soybean as
      well as goat's milk. The results obtained suggested that soybean and goat's milk
      may work as anti cancer agents in hepatocarcinogenesis although further studies
      are required to further elucidate this aspect.

PMID- 22973156
TI  - The effect of infinity-lipoic Acid in blood lipid levels and malondialdehyde in
      atherosclerotic-induced new zealand white rabbit.
AB  - infinity-Lipoic acid (ALA) is a naturally occuring cofactor that serves as an
      acyl carrier in oxidative decarboxylation of alpha-keto acids in carbohydrate
      metabolism. Current findings suggest that infinity-lipoic acid and its reduced
      form, dihydrolipoic acid (DHLA) may act as antioxidants and are able to quench
      free radicals in vitro and in vivo. However, the mechanism underlying the process
      is still unknown. In this study, atherosclerotic lesions were induced in six
      groups of adult male NZW rabbits labelled as group K, A, B, C, D, E (n=6) by
      giving 100g/head/day of 2% cholesterol-rich diet for ten weeks. While group K
      acted as a control, the rest were supplemented with ALA orally (1.4, 2.8, 4.2,
      8.0 and 10mg/kg, respectively). In week ten, venous blood samples drawn from ear
      lobes were analysed for complete lipid profile and peroxidation index. The
      results showed a significant reduction of total cholesterol (TC) and low density
      lipoprotein-cholesterol (LDL-C) levels in most of the treated groups as compared
      to the control whereas apo-A levels showed a significant increase in group C and
      D. However, microsomal lipid peroxidation index, malondialdehyde (MDA) was found
      to be not significantly different. These findings suggest that infinity-lipoic
      acid may act as a lipid lowering agent in dose dependent manner in premature
      stage of atherosclerosis but was unable to inhibit lipid peroxidation processes
      in matured stage of atherosclerosis in rabbits fed a high cholesterol diet.

PMID- 22973157
TI  - Detection of Vancomycin-Resistant Enterococcus Spp. (VRE) from Poultry.
AB  - Twenty-eight isolates of E. faecalis and 5 isolates of E. hirae were isolated
      from chicken samples obtained from markets in Sri Serdang, Selangor. They were
      tested for susceptibility to vancomycin and other antimicrobial agents. All of
      the isolates showed multiple resistance to the antibiotic tested. All
      Enterococcus spp. were resistant (100%) to ceftaxidime, cephalothin,
      erythromycin, gentamicin, kanamycin, nalidixic acid and streptomycin. Resistance
      was also observed to norfloxacin (97%), tetracycline (91%), penicillin (85%),
      bacitracin (82%), chloramphenicol (61%) and the least resistance was to
      ampicillin (27%). High prevalence to vancomycin resistance was detected among the
      E. faecalis (27of 28) and E. hirae (4 of 5) isolates. The multiple antibiotic
      resistance index ranging between 0.64 to 1.0 showed that all strains tested
      originated from high-risk contamination. Plasmid profile analysis of Enterococcus
      spp. revealed plasmid DNA bands ranging in size from 1.3 to 35.8 megadalton but
      some isolates were plasmidless. No correlation could be made between plasmid
      patterns and antibiotic resistance.

PMID- 22973158
TI  - Plasmid-mediated streptomycin resistance of listeria monocytogenes.
AB  - A strain of streptomycin-resistant Listeria monocytogenes LM35 isolated from
      imported frozen beef was examined in this study. In conjugation studies, the L.
      monocytogenes LM35 strain harbouring two plasmids of 54, 3.0, 2.8 and 2.7
      kilobase was used as the donor and streptomycin-sensitive and plasmidless L.
      monocytogenes LM65 and LM100 strains as the recipients. Streptomycin resistance
      was transferred to L. monocytogenes LM65 and LM100 strains at frequencies of 3.3
      * 10(-8) and 1.2 * 10(-9) per input donor cells, respectively. In both occasions,
      we also observed the concomitant transfer of the donor's 54 kilobase plasmid.
      These results suggest that streptomycin resistance in L. monocytogenes LM35 was
      mediated by the 54 kilobase plasmid.

PMID- 22973159
TI  - Bacteriocin-producing lactic Acid bacteria isolated from traditional fermented
      food.
AB  - Lactic Acid Bacteria (LAB) isolated from several traditional fermented foods such
      as "tempeh", "tempoyak" and "tapai" were screened for the production of
      bacteriocin. One strain isolated from "tempeh" gives an inhibitory activity
      against several LAB. The strain was later identified as Lactobacillus plantarum
      BS2. Study shows that the inhibitory activity was not caused by hydrogen
      peroxide, organic acids or bacteriophage. The bacteriocin production was maximum
      after 10 hours of incubation with an activity of 200 AU/ml. The bacteriocin was
      found to be sensitive towards trypsin, alpha-chymotrypsin, beta-chymotrypsin,
      alpha-amylase and lysozyme.

PMID- 22973160
TI  - Hepatoblastoma in a low birth weight infant : a case report and review of the
      literature.
AB  - Hepatoblastoma is the most common primary liver tumour of childhood. This is a
      case report of a one-year-old boy who presented with a one-month history of
      progressive abdominal distension and weight loss. He was cachexic, anaemic, had
      gross hepatomegaly and ascites. He had been born prematurely with a birth weight
      of 1.23 kg, and his developmental milestones were delayed. Ultrasound and CT scan
      demonstrated a large solid tumour in the left lobe of the liver with a smaller
      superficial nodule in the right lobe. Serum alpha fetoprotein was significantly
      raised. A left lobe hepatectomy and complete excision of the right sided nodule
      was performed. There was no evidence of metastatic disease. Histopathological
      examination confirmed hepatoblastoma of the fetal type. The patient developed
      features of intestinal obstruction a few days after surgery and he succumbed ten
      days after re-laparotomy. The clinical presentation and investigation results in
      this case are characteristic. Recent reports have suggested a strong relationship
      between very low birth weight (< 1500gm)/prematurity and hepatoblastoma as is
      present in this case. Surgery is the mainstay of therapy in hepatoblastoma. A
      brief review of the literature on this tumour is presented.

PMID- 22973161
TI  - Consumer understanding of sugars claims on food and drink products.
AB  - Consumer understanding of nutrition and health claims is a key aspect of current
      regulations in the European Union (EU). In view of this, qualitative and
      quantitative research techniques were used to investigate consumer awareness and
      understanding of product claims in the UK, focusing particularly on nutrition
      claims relating to sugars. Both research methods identified a good awareness of
      product claims. No added sugars claims were generally preferred to reduced sugars
      claims, and there was a general assumption that sweeteners and other ingredients
      would be added in place of sugars. However, there was little awareness of the
      level of sugar reduction and the associated calorie reduction in products when
      reduced sugars claims were made on pack. In focus groups, participants felt
      deceived if sugar reduction claims were being made without a significant
      reduction in calories. This was reinforced in the quantitative research which
      showed that respondents expected a similar and meaningful level of calorie
      reduction to the level of sugar reduction. The research also identified consumer
      confusion around the calorie content of different nutrients, including over
      estimation of the calorie content of sugars. This is crucial to consumers'
      expectations as they clearly link sugar to calories and therefore expect a
      reduction in sugar content to deliver a reduction in calorie content.

PMID- 22973162
TI  - Role of motif III in catalysis by acetyl-CoA synthetase.
AB  - The acyl-adenylate-forming enzyme superfamily, consisting of acyl- and aryl-CoA
      synthetases, the adenylation domain of the nonribosomal peptide synthetases, and
      luciferase, has three signature motifs (I-III) and ten conserved core motifs (A1
      A10), some of which overlap the signature motifs. The consensus sequence for
      signature motif III (core motif A7) in acetyl-CoA synthetase is Y-X-S/T/A-G-D,
      with an invariant fifth position, highly conserved first and fourth positions,
      and variable second and third positions. Kinetic studies of enzyme variants
      revealed that an alteration at any position resulted in a strong decrease in the
      catalytic rate, although the most deleterious effects were observed when the
      first or fifth positions were changed. Structural modeling suggests that the
      highly conserved Tyr in the first position plays a key role in active site
      architecture through interaction with a highly conserved active-site Gln, and the
      invariant Asp in the fifth position plays a critical role in ATP binding and
      catalysis through interaction with the 2'- and 3'-OH groups of the ribose moiety.
      Interactions between these Asp and ATP are observed in all structures available
      for members of the superfamily, consistent with a critical role in substrate
      binding and catalysis for this invariant residue.

PMID- 22973163
TI  - DNA binding in high salt: analysing the salt dependence of replication protein A3
      from the halophile Haloferax volcanii.
AB  - Halophilic archaea maintain intracellular salt concentrations close to saturation
      to survive in high-salt environments and their cellular processes have adapted to
      function under these conditions. Little is known regarding halophilic adaptation
      of the DNA processing machinery, particularly intriguing since protein-DNA
      interactions are classically salt sensitive. To investigate such adaptation, we
      characterised the DNA-binding capabilities of recombinant RPA3 from Haloferax
      volcanii (HvRPA3). Under physiological salt conditions (3 M KCl), HvRPA3 is
      monomeric, binding 18 nucleotide ssDNA with nanomolar affinity, demonstrating
      that RPAs containing the single OB-fold/zinc finger architecture bind with
      broadly comparable affinity to two OB-fold/zinc finger RPAs. Reducing the salt
      concentration to 1 M KCl induces dimerisation of the protein, which retains its
      ability to bind DNA. On circular ssDNA, two concentration-dependent binding modes
      are observed. Conventionally, increased salt concentration adversely affects DNA
      binding but HvRPA3 does not bind DNA in 0.2 M KCl, although multimerisation may
      occlude the binding site. The single N-terminal OB-fold is competent to bind DNA
      in the absence of the C-terminal zinc finger, albeit with reduced affinity. This
      study represents the first quantitative characterisation of DNA binding in a
      halophilic protein in extreme salt concentrations.

PMID- 22973164
TI  - HIV-1 replication in HIV-infected individuals is significantly reduced when
      peripheral blood mononuclear cells are superinfected with HSV-1.
AB  - Herpes simplex virus (HSV) can cause generalized infection in human
      immunodeficiency virus- (HIV-) infected patients leading to death. This study
      investigated HSV-1 replication in PBMCs from 25 HIV-infected individuals and 15
      healthy donors and the effects of HSV-1 superinfection on HIV-1 production.
      Herpes viral entry mediator (HVEM) receptor on T lymphocytes was also evaluated.
      Our results confirmed that the number of activated (CD3+ and CD38+) T lymphocytes
      in HIV-infected individuals (46.51 +/- 17.54%) was significantly higher than in
      healthy donors (27.54 +/- 14.12%, P value = 0.001) without any significant
      differences in HVEM expression. Even though the percentages of HSV-1 infected T
      lymphocytes between HIV-infected individuals (79.25 +/- 14.63%) and healthy
      donors (80.76 +/- 7.13%) were not different (P value = 0.922), yet HSV-1
      production in HIV-infected individuals (47.34 +/- 11.14 * 103 PFU/ml) was
      significantly greater than that of healthy donors (34.17 +/- 8.48 * 103 PFU/ml, P
      value = 0.001). Moreover, HSV-1 virions were released extracellularly rather than
      being associated with the cells, and superinfection of HSV-1 at a multiplicity of
      infection (MOI) of 5 significantly decreased HIV production (P value < 0.001).

PMID- 22973165
TI  - Restructuring BOD : COD ratio of dairy milk industrial wastewaters in BOD
      analysis by formulating a specific microbial seed.
AB  - BOD (Biochemical oxygen demand) is the pollution index of any water sample. One
      of the main factors influencing the estimation of BOD is the nature of
      microorganisms used as seeding material. In order to meet the variation in
      wastewater characteristics, one has to be specific in choosing the biological
      component that is the seeding material. The present study deals with the
      estimation of BOD of dairy wastewater using a specific microbial consortium and
      compares of the results with seeding material (BODSEED). Bacterial strains were
      isolated from 5 different sources and were screened by the conventional BOD
      method. The selected microbial seed comprises of Enterobacter sp., Pseudomonas
      sp. BOD : COD (Chemical oxygen demand) ratio using the formulated seed comes in
      the range of 0.7-0.8 whereas that using BODSEED comes in the ratio of 0.5-0.6.
      The ultimate BOD (UBOD) was also performed by exceeding the 3-day dilution BOD
      test. After 90 days, it has been observed that the ratio of BOD : COD increased
      in case of selected consortium 7 up to 0.91 in comparison to 0.74 by BODSEED. The
      results were analyzed statistically by t-test and it was observed that selected
      consortium was more significant than the BODSEED.

PMID- 22973166
TI  - Colistin resistance in Escherichia coli and Salmonella enterica strains isolated
      from swine in Brazil.
AB  - Reports about acquired resistance to colistin in different bacteria species are
      increasing, including E. coli of animal origin, but reports of resistance in wild
      S. enterica of different serotypes from swine are not found in the literature.
      Results obtained with one hundred and twenty-six E. coli strains from diseased
      swine and one hundred and twenty-four S. enterica strains from diseased and
      carrier swine showed a frequency of 6.3% and 21% of colistin-resistant strains,
      respectively. When comparing the disk diffusion test with the agar dilution test
      to evaluate the strains, it was confirmed that the disk diffusion test is not
      recommended to evaluate colistin resistance as described previously. The colistin
      MIC 90 and MIC 50 values obtained to E. coli were 0.25 MUg/mL and 0.5 MUg/mL, the
      MIC 90 and MIC 50 to S. enterica were 1 MUg/mL and 8 MUg/mL. Considering the
      importance of colistin in control of nosocomial human infections with Gram
      negative multiresistant bacteria, and the large use of this drug in animal
      production, the colistin resistance prevalence in enterobacteriaceae of animal
      origin must be monitored more closely.

PMID- 22973167
TI  - Reflective journals of students taking a positive youth-development course in a
      university context in Hong Kong.
AB  - To promote the holistic development of university students, a course entitled
      "Tomorrow's Leaders" was developed and offered at The Hong Kong Polytechnic
      University. Based on a case study approach, reflective journals of five
      outstanding students of the course are presented and analyzed (i.e., thick
      description), with several themes emerging from the reflection. First, the
      students liked the course, and they identified many positive attributes. Second,
      the students appreciated the instructors. Third, the students viewed that the
      course contributed to different aspects of their development. Fourth, some areas
      of improvements were proposed. In conjunction with other evaluation mechanisms,
      the present findings strongly suggest that the course is able to promote
      psychosocial competencies in university students taking this course.

PMID- 22973168
TI  - Effect of repositioning maneuver type and postmaneuver restrictions on vertigo
      and dizziness in benign positional paroxysmal vertigo.
AB  - INTRODUCTION: To compare the efficiency of Epley (Ep) and Semont-Toupet (ST)
      repositioning maneuvers and to evaluate postmaneuver restriction effect on short
      term vertigo and dizziness after repositioning maneuvers by an analog visual
      scale (VAS) in benign positional paroxysmal vertigo (BPPV). MATERIAL AND METHODS:
      226 consecutive adult patients with posterior canal BPPV were included. Patients
      were randomized into 2 different maneuver sequence groups (n = 113): 2 ST then 1
      Ep or 2 Ep then 1 ST. Each group of sequence was randomized into 2 subgroups:
      with or without postmaneuver restrictions. Vertigo and dizziness were assessed
      from days 0 to 5 by VAS. RESULTS: There was no difference between vertigo scores
      between Ep and ST groups. Dizziness scores were higher in Ep group during the
      first 3 days but became similar to those of ST group at days 4 and 5. ST
      maneuvers induced liberatory signs more frequently than Ep (58% versus 42% resp.,
      P < 0.01, Fisher's test). After repositioning maneuvers, VAS scores decreased
      similarly in patients with and without liberatory signs. Postmaneuver
      restrictions did not influence VAS scores. CONCLUSION: Even if ST showed a higher
      rate of liberatory signs than Ep in this series, VAS scores were not influenced
      by these signs.

PMID- 22973169
TI  - Temozolomide as second or third line treatment of patients with neuroendocrine
      carcinomas.
AB  - BACKGROUND: Knowledge of the clinical efficacy in recurrent neuroendocrine
      carcinomas is sparse. Treatment with temozolomide alone or in combination with
      capecitabine and bevacizumab has recently shown promising results. PATIENTS AND
      METHODS: Analysis of consecutive patients with neuroendocrine carcinomas (Ki-67
      proliferation index >20%) and performance status 0-2 treated with temozolomide
      200 mg/sqm orally days 1-5 every 28 days after at least one previous platin
      containing chemotherapy regimen. RESULTS: Twenty-eight eligible patients received
      a median of 3 courses. Sixteen patients were evaluable for response: Six achieved
      stable disease and ten progressed. The median survival for the 28 patients was
      3.5 months. Survival in patients with tumors of pancreatic origin (n = 7) was 7.0
      months versus 2.9 months in non-pancreatic origin (n = 21). Patients in PS 0-1 (n
      = 22) had a median survival of 4.5 months versus 1.1 months in patients in PS 2
      (n = 6). Ki-67 index >= 50% was associated with a significantly shorter median
      survival than Ki-67 index <50% (2.7 months versus 10.9 months). The treatment was
      well tolerated. CONCLUSION: Temozolomide monotherapy has limited effect in
      treatment of recurrent neuroendocrine carcinomas. Second line treatment with
      temozolomide in combination with other compounds should be further investigated
      in patients in good performance with Ki-67 index <50%.

PMID- 22973170
TI  - T2-weighted cardiac magnetic resonance imaging of edema in myocardial diseases.
AB  - The purpose of this paper is to describe imaging techniques and findings of T2
      weighted magnetic resonance imaging (MRI) of edema in myocardial diseases. T2
      weighted cardiac MRI is acquired by combining acceleration techniques with motion
      and signal suppression techniques. The MRI findings should be interpreted based
      on coronary artery supply, intramural distribution, and comparison with delayed
      enhancement MRI. In acute myocardial diseases, such as acute myocardial
      infarction and myocarditis, the edema is larger than myocardial scarring, whereas
      the edema can be smaller than the scarring in some types of nonischemic
      cardiomyopathy, including hypertrophic cardiomyopathy. T2-weighted MRI of edema
      identifies myocardial edema associated with ischemia, inflammation, vasculitis,
      or intervention in the myocardium and provides information complementary to
      delayed-enhancement MRI.

PMID- 22973171
TI  - Metabolic syndrome, hormone levels, and inflammation in patients with erectile
      dysfunction.
AB  - BACKGROUND: The end point of this study was to investigate the prevalence of MS
      in patients with ED in comparison with control subjects and to analyse the
      association with acute phase reactants (CRP, ESR) and hormone levels. METHODS:
      This case-control study included 65 patients, 37 with erectile dysfunction,
      according to the International Index of Erectile Function (IIEF) from the Urology
      Department of San Cecilio University Hospital, Granada (Spain) and 28 healthy
      controls. The prevalence of metabolic syndrome was calculated according to ATP
      III criteria. Hormone levels and acute phase parameters were studied in samples
      drawn. RESULTS: The ATP-III criteria for MS were met by 64.9% of the patients
      with ED and only 9.5% of the controls (P < 0.0001, OR = 17.53, 95% CI: 3.52
      87.37). Binary logistic regression analysis showed a strong association between
      patients with ED and MS, even after additional adjustment for confounding factors
      (OR = 20.05, 95% CI: 1.24-32.82, P < 0.034). Patients with hypogonadism presented
      a significantly higher prevalence of metabolic syndrome. Multiple linear
      regression analysis showed that systolic BP and CRP predicted 0.46 (model R2) of
      IIEF changes. CONCLUSION: Chronic inflammation found in patients with ED might
      explain the association between ED and metabolic syndrome.

PMID- 22973172
TI  - Evaluation of histopathological changes in control biopsies which taken 48
      sessions after NBUVB phototherapy for early-stage mycosis fungoides.
AB  - BACKGROUND: There are not many studies investigating histomorphological changes
      in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB)
      treatment. Our purpose is to evaluate histological features of phototherapy after
      48 sessions and determine which parameters are more reliable for controlling skin
      biopsies. METHODS: Biopsies of 32 patients with early stage of MF, who were
      treated with NBUVB phototherapy, were histologically evaluated before and after
      the treatments, including epidermotropism, stratum corneum, epidermal thickness,
      dermal infiltration, papillary dermal fibrosis, vascular alterations, and other
      dermal changes. We discuss the histomorphological effects of NBUVB phototherapy
      on skin biopsies by comparing the responders with nonresponders, with before and
      after the treatment. RESULTS: 9 patients (28%) did not give any response to
      treatment. Alleviation in epidermotropism, increases in parakeratosis and normal
      keratosis, perivascular infiltration, and melanophages, decrease in the
      lichenoid/patchy lichenoid infiltration pattern after the treatment was
      statistically significant. Comparing by response, normalization of stratum
      corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells,
      the lichenoid/patchy lichenoid infiltration, the loss of inflammation were
      statistically significant in responders group. CONCLUSION: We detected a
      significant decrease in linearly arranged cells after phototherapy, indicating
      that it is an "important diagnostic parameter" in evaluation of therapeutic
      response.

PMID- 22973173
TI  - Antileishmanial activity of warifteine: a bisbenzylisoquinoline alkaloid isolated
      from Cissampelos sympodialis Eichl. (Menispermaceae).
AB  - Leishmania (L.) chagasi is the etiological agent of visceral leishmaniasis, an
      important endemic zoonosis in the American continent, as well as in many other
      countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult
      due to the high toxicity of the available drugs, high costs, and emergence of
      resistance in the parasites. Therefore, there is an urgent need for new
      leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to
      antibacterial, antiprotozoal, and antifungal activities. The aim of this study
      was to evaluate the growth inhibitory activity of warifteine
      (bisbenzylisoquinoline alkaloid) against L. chagasi promastigotes in axenic
      cultures and the occurrence of drug-induced ultrastructural changes in the
      parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and
      roots of Cissampelos sympodialis Eichl. (Menispermaceae), a plant commonly used
      for the treatment of various diseases in Brazilian folk medicine. Using the
      purified warifteine, the 50% inhibitory concentration (IC50) was determined at
      0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite
      morphology, like aberrant multisepted forms and blebs in the plasma membrane. In
      conclusion, warifteine represents an attractive candidate for future
      pharmacological studies aiming new leishmanicidal drugs.

PMID- 22973174
TI  - An assessment of whole blood and fractions by nested PCR as a DNA source for
      diagnosing canine ehrlichiosis and anaplasmosis.
AB  - Ehrlichiosis and anaplasmosis are tick-borne diseases. Ehrlichia canis and
      Anaplasma platys infect mainly white cells and platelets, respectively. The main
      DNA source for PCR is peripheral blood, but the potential of blood cell fractions
      has not been extensively investigated. This study aims at assessment of whole
      blood (WB) and blood fractions potential in nested PCR (nPCR) to diagnose canine
      ehrlichiosis and anaplasmosis. The 16S rRNA gene was amplified in 71.4, 17.8,
      31.57, and 30% of the WB, granulocyte (G), mononuclear cells (M), and buffy coat
      (BC) samples. Compared to the WB, the sensitivity of the PCR was 42.86% for the
      M, and BC fractions, 21.43% for the G, and 33.33% for the blood clot (C). There
      was fair agreement between the WB and M, BC and C, and slight with the G. Fair
      agreement occurred between the nPCR and morulae in the blood smear. One animal
      was coinfected with A. platys and E. canis. This study provided the first
      evidence of A. platys infection in dogs in Paraiba, Brazil, and demonstrated that
      WB is a better DNA source than blood fractions to detect Ehrlichia and Anaplasma
      by nPCR, probably because of the plasma bacterial concentration following host
      cell lysis.

PMID- 22973175
TI  - MATN3 gene polymorphism is associated with osteoarthritis in Chinese Han
      population: a community-based case-control study.
AB  - BACKGROUND: The matrilin, especially matrilin-3 (MATN3), are reported to play
      important roles in the pathophysiology of osteoarthritis (OA). To explore the
      relationship between MATN3 SNP6 (rs8176070) and primary OA, we conducted a
      community-based case-control study. METHODS: A total of 732 community residents
      aged 40-84 years participated in the community-based study in Northeast China.
      After taking physical and radiographic examinations, 420 of the residents were
      diagnosed OA (216 women and 204 men). The other 312 individuals without any
      symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men)
      were considered as healthy controls. After obtaining the DNA of case and control
      groups, genotypes of the MATN3 SNP6 were determined by polymerase chain reaction
      followed by restriction enzyme digestion. The numbers of patients with different
      OA subtypes were also calculated. RESULTS: The distribution of genotypes and
      alleles of the MATN3 SNP6 between OA patients and controls was different
      significantly. The BB carrier tends to be associated with the increased
      osteoarthritis (P = 0.025, OR = 1.724, 95% CI = 1.071-2.77), especially the knee
      osteoarthritis (P = 0.021, OR = 2.402, 95% CI = 1.141-5.060) and lumber
      osteoarthritis (P = 0.020, OR = 1.880, 95% CI = 1.103-3.204). Bb carrier
      increased hand osteoarthritis risk (P = 0.002, OR = 5.380, 95% CI = 1.828
      15.835). The B allele might have an effect on the increased knee osteoarthritis
      (P = 0.000, OR = 3.143, 95% CI = 2.283-4.328). CONCLUSION: These findings suggest
      that the MATN3 gene polymorphism might be associated with osteoarthritis in the
      Chinese Han population.

PMID- 22973176
TI  - Exergetic assessment for resources input and environmental emissions by Chinese
      industry during 1997-2006.
AB  - This paper presents an overview of the resources use and environmental impact of
      the Chinese industry during 1997-2006. For the purpose of this analysis the
      thermodynamic concept of exergy has been employed both to quantify and aggregate
      the resources input and the environmental emissions arising from the sector. The
      resources input and environmental emissions show an increasing trend in this
      period. Compared with 47568.7 PJ in 1997, resources input in 2006 increased by
      75.4% and reached 83437.9 PJ, of which 82.5% came from nonrenewable resources,
      mainly from coal and other energy minerals. Furthermore, the total exergy of
      environmental emissions was estimated to be 3499.3 PJ in 2006, 1.7 times of that
      in 1997, of which 93.4% was from GHG emissions and only 6.6% from "three wastes"
      emissions. A rapid increment of the nonrenewable resources input and GHG
      emissions over 2002-2006 can be found, owing to the excessive expansion of
      resource- and energy-intensive subsectors. Exergy intensities in terms of
      resource input intensity and environmental emission intensity time-series are
      also calculated, and the trends are influenced by the macroeconomic situation
      evidently, particularly by the investment-derived economic development in recent
      years. Corresponding policy implications to guide a more sustainable industry
      system are addressed.

PMID- 22973177
TI  - Comparison of central macular thickness measured by three OCT models and study of
      interoperator variability.
AB  - PURPOSE: To compare central macular thickness (CMT) measurement on healthy
      patient using 3 different OCT devices by two operators. METHODS: Prospective,
      monocentricstudy. Right eye's central macular thickness (CMT) of 30 healthy
      patients has been measured three times using a time-domain (TD) OCT (Stratus OCT,
      Carl Zeiss Meditec, Dublin, Ca) and two spectral domain (SD) OCTs (Cirrus HD-OCT,
      Carl ZeissMeditec, Dublin, Ca) and 3D-OCT 1000 (Topcon, Tokyo, Japan) by two
      operators. Six measurements were taken randomly for each patient the same day.
      RESULTS: No significant difference between measurements obtained by the two
      operators has been observed, whatever the studied OCT. P value was 0.164, 0.193,
      and 0.147 for Stratus OCT, Cirrus HD-OCT and 3D-OCT, respectively. Mean CMT
      significantly differed from instrument to instrument (P < 0.001) and was,
      respectively, 197 MUm, 254 MUm, and 236 MUm using Stratus OCT, Cirrus HD-OCT, and
      3D-OCT 1000. Using Cirrus OCT and 3D-OCT 1000, CMT was, respectively, 57 MUm and
      39 MUm thicker than using Stratus OCT (P < 0.05). CONCLUSIONS: Whatever the OCT
      device, on healthy patients CMT was not operator dependent. CMT measurements
      obtained by SD-OCTs are greater than those obtained by TD-OCT. These data imply
      that the different OCT devices cannot be used interchangeably in clinical
      monitoring.

PMID- 22973178
TI  - Correlation of surgical pleth index with stress hormones during propofol
      remifentanil anaesthesia.
AB  - Eighty patients undergoing elective ear-nose-throat surgery were enrolled in the
      present study to investigate the relationship between surgical pleth index (SPI)
      and stress hormones (ACTH, cortisol, epinephrine, norepinephrine) during general
      anaesthesia which was induced and maintained with propofol and remifentanil using
      a target-controlled infusion. The study concluded that the SPI had moderate
      correlation to the stress hormones during general anaesthesia, but no correlation
      during consciousness. Furthermore, SPI values were able to predict ACTH values
      with high sensitivity and specificity.

PMID- 22973179
TI  - The effect of the weight of equipment on muscle activity of the lower extremity
      in soldiers.
AB  - Due to their profession and the tasks it entails, soldiers are exposed to high
      levels of physical activity and strain. This can result in overexertion and pain
      in the locomotor system, partly caused by carrying items of equipment. The aim of
      this study was to analyse the extent of muscle activity in the lower extremities
      caused by carrying specific items of equipment. For this purpose, the activity of
      selected groups of muscles caused by different items of equipment (helmet,
      carrying strap, backpack, and rifle) in the upper and lower leg was measured by
      recording dynamic surface electromyograms. Electrogoniometers were also used to
      measure the angle of the knee over the entire gait cycle. In addition to
      measuring muscle activity, the study also aimed to determine out what influence
      increasing weight load has on the range of motion (ROM) of the knee joint during
      walking. The activity of recorded muscles of the lower extremity, that is, the
      tibialis anterior, peroneus longus, gastrocnemius lateralis, gastrocnemius
      medialis, rectus femoris, and biceps femoris, was found to depend on the weight
      of the items of equipment. There was no evidence, however, that items of
      equipment weighing a maximum of 34% of their carrier's body weight had an effect
      on the ROM of the knee joint.

PMID- 22973180
TI  - Smooth muscle tension induces invasive remodeling of the zebrafish intestine.
AB  - The signals that initiate cell invasion are not well understood, but there is
      increasing evidence that extracellular physical signals play an important role.
      Here we show that epithelial cell invasion in the intestine of zebrafish meltdown
      (mlt) mutants arises in response to unregulated contractile tone in the
      surrounding smooth muscle cell layer. Physical signaling in mlt drives formation
      of membrane protrusions within the epithelium that resemble invadopodia, matrix
      degrading protrusions present in invasive cancer cells. Knockdown of Tks5, a Src
      substrate that is required for invadopodia formation in mammalian cells blocked
      formation of the protrusions and rescued invasion in mlt. Activation of Src
      signaling induced invadopodia-like protrusions in wild type epithelial cells,
      however the cells did not migrate into the tissue stroma, thus indicating that
      the protrusions were required but not sufficient for invasion in this in vivo
      model. Transcriptional profiling experiments showed that genes responsive to
      reactive oxygen species (ROS) were upregulated in mlt larvae. ROS generators
      induced invadopodia-like protrusions and invasion in heterozygous mlt larvae but
      had no effect in wild type larvae. Co-activation of oncogenic Ras and Wnt
      signaling enhanced the responsiveness of mlt heterozygotes to the ROS generators.
      These findings present the first direct evidence that invadopodia play a role in
      tissue cell invasion in vivo. In addition, they identify an inducible physical
      signaling pathway sensitive to redox and oncogenic signaling that can drive this
      process.

PMID- 22973181
TI  - Gender differences in survival among adult patients starting antiretroviral
      therapy in South Africa: a multicentre cohort study.
AB  - BACKGROUND: Increased mortality among men on antiretroviral therapy (ART) has
      been documented but remains poorly understood. We examined the magnitude of and
      risk factors for gender differences in mortality on ART. METHODS AND FINDINGS:
      Analyses included 46,201 ART-naive adults starting ART between January 2002 and
      December 2009 in eight ART programmes across South Africa (SA). Patients were
      followed from initiation of ART to outcome or analysis closure. The primary
      outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic
      suppression, and CD4+ cell count responses. Survival analyses were used to
      examine the hazard of death on ART by gender. Sensitivity analyses were limited
      to patients who were virologically suppressed and patients whose CD4+ cell count
      reached >200 cells/ul. We compared gender differences in mortality among HIV+
      patients on ART with mortality in an age-standardised HIV-negative population.
      Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years
      of follow-up, men had lower median CD4+ cell counts than women (85 versus 110
      cells/ul, p<0.001), were more likely to be classified WHO stage III/IV (86 versus
      77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100
      person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31,
      95% CI 1.22-1.41). After 36 months on ART, men were more likely than women to be
      truly LTF (AHR 1.20, 95% CI 1.12-1.28) but not to die after LTF (AHR 1.04, 95% CI
      0.86-1.25). Findings were consistent across all eight programmes. Virologic
      suppression was similar by gender; women had slightly better immunologic
      responses than men. Notably, the observed gender differences in mortality on ART
      were smaller than gender differences in age-standardised death rates in the HIV
      negative South African population. Over time, non-HIV mortality appeared to
      account for an increasing proportion of observed mortality. The analysis was
      limited by missing data on baseline HIV disease characteristics, and we did not
      observe directly mortality in HIV-negative populations where the participating
      cohorts were located. CONCLUSIONS: HIV-infected men have higher mortality on ART
      than women in South African programmes, but these differences are only partly
      explained by more advanced HIV disease at the time of ART initiation,
      differential LTF and subsequent mortality, and differences in responses to
      treatment. The observed differences in mortality on ART may be best explained by
      background differences in mortality between men and women in the South African
      population unrelated to the HIV/AIDS epidemic. Please see later in the article
      for the Editors' Summary.

PMID- 22973182
TI  - Reduced risk of Plasmodium vivax malaria in Papua New Guinean children with
      Southeast Asian ovalocytosis in two cohorts and a case-control study.
AB  - BACKGROUND: The erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO)
      (which results from a 27-base pair deletion in the erythrocyte band 3 gene,
      SLC4A1Delta27) protects against cerebral malaria caused by Plasmodium falciparum;
      however, it is unknown whether this polymorphism also protects against P. vivax
      infection and disease. METHODS AND FINDINGS: The association between SAO and P.
      vivax infection was examined through genotyping of 1,975 children enrolled in
      three independent epidemiological studies conducted in the Madang area of Papua
      New Guinea. SAO was associated with a statistically significant 46% reduction in
      the incidence of clinical P. vivax episodes (adjusted incidence rate ratio [IRR]
      = 0.54, 95% CI 0.40-0.72, p<0.0001) in a cohort of infants aged 3-21 months and a
      significant 52% reduction in P. vivax (blood-stage) reinfection diagnosed by PCR
      (95% CI 22-71, p = 0.003) and 55% by light microscopy (95% CI 13-77, p = 0.014),
      respectively, in a cohort of children aged 5-14 years. SAO was also associated
      with a reduction in risk of P. vivax parasitaemia in children 3-21 months
      (1,111/ul versus 636/ul, p = 0.011) and prevalence of P. vivax infections in
      children 15-21 months (odds ratio [OR] = 0.39, 95% CI 0.23-0.67, p = 0.001). In a
      case-control study of children aged 0.5-10 years, no child with SAO was found
      among 27 cases with severe P. vivax or mixed P. falciparum/P. vivax malaria (OR =
      0, 95% CI 0-1.56, p = 0.11). SAO was associated with protection against severe P.
      falciparum malaria (OR = 0.38, 95% CI 0.15-0.87, p = 0.014) but no effect was
      seen on either the risk of acquiring blood-stage infections or uncomplicated
      episodes with P. falciparum. Although Duffy antigen receptor expression and
      function were not affected on SAO erythrocytes compared to non-SAO children, high
      level (>90% binding inhibition) P. vivax Duffy binding protein-specific binding
      inhibitory antibodies were observed significantly more often in sera from SAO
      than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; p = 0.008). CONCLUSIONS: In
      three independent studies, we observed strong associations between SAO and
      protection against P. vivax malaria by a mechanism that is independent of the
      Duffy antigen. P. vivax malaria may have contributed to shaping the unique host
      genetic adaptations to malaria in Asian and Oceanic populations. Please see later
      in the article for the Editors' Summary.

PMID- 22973183
TI  - Point-of-care testing for infectious diseases: diversity, complexity, and
      barriers in low- and middle-income countries.

PMID- 22973185
TI  - Attitudes of older adults toward shooter video games: An initial study to select
      an acceptable game for training visual processing.
AB  - A computer-based 'Useful Field of View' (UFOV) training program has been shown to
      be effective in improving visual processing in older adults. Studies of young
      adults have shown that playing video games can have similar benefits; however,
      these studies involved realistic and violent 'first-person shooter' (FPS) games.
      The willingness of older adults to play such games has not been established.
      OBJECTIVES: To determine the degree to which older adults would accept playing a
      realistic, violent FPS-game, compared to video games not involving realistic
      depiction of violence.  METHODS: Sixteen older adults (ages 64-77) viewed and
      rated video-clip demonstrations of the UFOV program and three video-game genres
      (realistic-FPS, cartoon-FPS, fixed-shooter), and were then given an opportunity
      to try them out (30 minutes per game) and rate various features.  RESULTS: The
      results supported a hypothesis that the participants would be less willing to
      play the realistic-FPS game in comparison to the less violent alternatives
      (p's<0.02). After viewing the video-clip demonstrations, 10 of 16 participants
      indicated they would be unwilling to try out the realistic-FPS game. Of the six
      who were willing, three did not enjoy the experience and were not interested in
      playing again. In contrast, all 12 subjects who were willing to try the cartoon
      FPS game reported that they enjoyed it and would be willing to play again. A high
      proportion also tried and enjoyed the UFOV training (15/16) and the fixed-shooter
      game (12/15).  DISCUSSION: A realistic, violent FPS video game is unlikely to be
      an appropriate choice for older adults. Cartoon-FPS and fixed-shooter games are
      more viable options. Although most subjects also enjoyed UFOV training, a video
      game approach has a number of potential advantages (for instance, 'addictive'
      properties, low cost, self-administration at home). We therefore conclude that
      non-violent cartoon-FPS and fixed-shooter video games warrant further
      investigation as an alternative to the UFOV program for training improved visual
      processing in seniors.

PMID- 22973184
TI  - Performance limitations of relay neurons.
AB  - Relay cells are prevalent throughout sensory systems and receive two types of
      inputs: driving and modulating. The driving input contains receptive field
      properties that must be transmitted while the modulating input alters the
      specifics of transmission. For example, the visual thalamus contains relay
      neurons that receive driving inputs from the retina that encode a visual image,
      and modulating inputs from reticular activating system and layer 6 of visual
      cortex that control what aspects of the image will be relayed back to visual
      cortex for perception. What gets relayed depends on several factors such as
      attentional demands and a subject's goals. In this paper, we analyze a
      biophysical based model of a relay cell and use systems theoretic tools to
      construct analytic bounds on how well the cell transmits a driving input as a
      function of the neuron's electrophysiological properties, the modulating input,
      and the driving signal parameters. We assume that the modulating input belongs to
      a class of sinusoidal signals and that the driving input is an irregular train of
      pulses with inter-pulse intervals obeying an exponential distribution. Our
      analysis applies to any [Formula: see text] order model as long as the neuron
      does not spike without a driving input pulse and exhibits a refractory period.
      Our bounds on relay reliability contain performance obtained through simulation
      of a second and third order model, and suggest, for instance, that if the
      frequency of the modulating input increases or the DC offset decreases, then
      relay increases. Our analysis also shows, for the first time, how the biophysical
      properties of the neuron (e.g. ion channel dynamics) define the oscillatory
      patterns needed in the modulating input for appropriately timed relay of sensory
      information. In our discussion, we describe how our bounds predict experimentally
      observed neural activity in the basal ganglia in (i) health, (ii) in Parkinson's
      disease (PD), and (iii) in PD during therapeutic deep brain stimulation. Our
      bounds also predict different rhythms that emerge in the lateral geniculate
      nucleus in the thalamus during different attentional states.

PMID- 22973186
TI  - A New System and Paradigm for Chronic Stimulation of Denervated Rat Muscle.
AB  - Traditionally, animal studies employing electrical stimulation for conditioning
      denervated muscle rely on 24-hour-based stimulation paradigms, most employing
      implantable stimulators. While these stimulators provide the necessary current to
      cause muscular contraction, they have problems with battery life,
      programmability, and long-term robustness. Continuous 24-hour stimulation, while
      shown to be effective in animals, is not easily translatable to a clinical
      setting. It is also difficult to evaluate animal comfort and muscular contraction
      throughout a 24-hour period. We have developed a system and stimulation paradigm
      that can stimulate up to five animals at one time for one hour per day. The
      constant current stimulator is a USB-powered device that can, under computer
      control, output trains of pulses with selectable shapes, widths, durations and
      repetition rates. It is an external device with no implantable parts in the
      animal except for the stimulating electrodes. We tested the system on two groups
      of rats with denervated gastrocnemius muscles. One group was stimulated using a
      one-hour-per-day, 5-days-per-week stimulation paradigm for one month, while the
      other group had electrodes implanted but received no stimulation. Muscle weight
      and twitch force were significantly larger in the stimulated group than the non
      stimulated group. Presently, we are using the stimulator to investigate
      electrical stimulation coupled with other therapeutic interventions that can
      minimize functional deficits after peripheral nerve injuries.

PMID- 22973188
TI  - Optimal short-sighted rules.
AB  - The aim of this paper is to assess the relevance of methodological transfers from
      behavioral ecology to experimental economics with respect to the elicitation of
      intertemporal preferences. More precisely our discussion will stem from the
      analysis of Stephens and Anderson's (2001) seminal article. In their study with
      blue jays they document that foraging behavior typically implements short-sighted
      choice rules which are beneficial in the long run. Such long-term profitability
      of short-sighted behavior cannot be evidenced when using a self-control paradigm
      (one which contrasts in a binary way sooner smaller and later larger payoffs) but
      becomes apparent when ecological patch-paradigms (replicating economic situations
      in which the main trade-off consists in staying on a food patch or leaving for
      another patch) are implemented. We transfer this methodology in view of
      contrasting foraging strategies and self-control in human intertemporal choices.

PMID- 22973187
TI  - Decision Making and Behavioral Choice during Predator Avoidance.
AB  - One of the most important decisions animals have to make is how to respond to an
      attack from a potential predator. The response must be prompt and appropriate to
      ensure survival. Invertebrates have been important models in studying the
      underlying neurobiology of the escape response due to their accessible nervous
      systems and easily quantifiable behavioral output. Moreover, invertebrates
      provide opportunities for investigating these processes at a level of analysis
      not available in most other organisms. Recently, there has been a renewed focus
      in understanding how value-based calculations are made on the level of the
      nervous system, i.e., when decisions are made under conflicting circumstances,
      and the most desirable choice must be selected by weighing the costs and benefits
      for each behavioral choice. This article reviews samples from the current
      literature on anti-predator decision making in invertebrates, from single neurons
      to complex behaviors. Recent progress in understanding the mechanisms underlying
      value-based behavioral decisions is also discussed.

PMID- 22973189
TI  - The road not taken: neural correlates of decision making in orbitofrontal cortex.
AB  - Empirical research links human orbitofrontal cortex (OFC) to the evaluation of
      outcomes during decision making and the representation of alternative (better)
      outcomes after failures. When faced with a difficult decision, rats sometimes
      pause and turn back-and-forth toward goals, until finally orienting toward the
      chosen direction. Neural representations of reward in rodent OFC increased
      immediately following each reorientation, implying a transient representation of
      the expected outcome following self-initiated decisions. Upon reaching reward
      locations and finding no reward (having made an error), OFC representations of
      reward decreased locally indicating a disappointment signal that then switched to
      represent the unrewarded, non-local, would-have-been rewarded site. These results
      illustrate that following a decision to act, neural ensembles in OFC represent
      reward, and upon the realization of an error, represent the reward that could
      have been.

PMID- 22973191
TI  - The Neuronal Functions of EF-Hand Ca2+-Binding Proteins.

PMID- 22973190
TI  - Stress and addiction: contribution of the corticotropin releasing factor (CRF)
      system in neuroplasticity.
AB  - Corticotropin releasing factor (CRF) has been shown to induce various behavioral
      changes related to adaptation to stress. Dysregulation of the CRF system at any
      point can lead to a variety of psychiatric disorders, including substance use
      disorders (SUDs). CRF has been associated with stress-induced drug reinforcement.
      Extensive literature has identified CRF to play an important role in the
      molecular mechanisms that lead to an increase in susceptibility that precipitates
      relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the
      acute effects of drugs of abuse and is also responsible for the potentiation of
      drug-induced neuroplasticity evoked during the withdrawal period. We present in
      this review the brain regions and circuitries where CRF is expressed and may
      participate in stress-induced drug abuse. Finally, we attempt to evaluate the
      role of modulating the CRF system as a possible therapeutic strategy for treating
      the dysregulation of emotional behaviors that result from the acute positive
      reinforcement of substances of abuse as well as the negative reinforcement
      produced by withdrawal.

PMID- 22973192
TI  - Refuting the challenges of the developmental shift of polarity of GABA actions:
      GABA more exciting than ever!
AB  - DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR
      CHLORIDE ASSOCIATED WITH A SHIFT IN GABA POLARITY: GABA depolarizes and
      occasionally excites immature neurons, subsequently hyperpolarizing them at later
      stages of development. This sequence, which has been observed in a wide range of
      animal species, brain structures and preparations, is thought to play an
      important role in activity-dependent formation and modulation of functional
      circuits. This sequence has also been considerably reinforced recently with new
      data pointing to an evolutionary preserved rule. In a recent "Hypothesis and
      Theory Article," the excitatory action of GABA in early brain development is
      suggested to be "an experimental artefact" (Bregestovski and Bernard, 2012). The
      authors suggest that the excitatory action of GABA is due to an
      inadequate/insufficient energy supply in glucose-perfused slices and/or to the
      damage produced by the slicing procedure. However, these observations have been
      repeatedly contradicted by many groups and are inconsistent with a large body of
      evidence including the fact that the developmental shift is neither restricted to
      slices nor to rodents. We summarize the overwhelming evidence in support of both
      excitatory GABA during development, and the implications this has in
      developmental neurobiology.

PMID- 22973194
TI  - Pressure-selective modulation of NMDA receptor subtypes may reflect 3D structural
      differences.
AB  - Professional deep-water divers exposed to high pressure (HP) above 1.1 MPa suffer
      from High Pressure Neurological Syndrome (HPNS), which is associated with CNS
      hyperexcitability. We have previously reported that HP augments N-methyl-D
      aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability,
      and potentially causes irreversible neuronal damage. We now report that HP (10.1
      MPa) differentially affects eight specific NMDAR subtypes. GluN1(1a or 1b) was co
      expressed with one of the four GluN2(A-D) subunits in Xenopus laevis oocytes. HP
      increased ionic currents (measured by two electrode voltage clamps) of one
      subtype, reduced the current in four others, and did not affect the current in
      the remaining three. 3D theoretical modeling was aimed at revealing specific
      receptor domains involved with HP selectivity. In light of the information on the
      CNS spatial distribution of the different NMDAR subtypes, we conclude that the
      NMDAR's diverse responses to HP may lead to selective HP effects on different
      brain regions. These discoveries call for further and more specific investigation
      of deleterious HP effects and suggest the need for a re-evaluation of deep-diving
      safety guidelines.

PMID- 22973193
TI  - Implications of aneuploidy for stem cell biology and brain therapeutics.
AB  - Understanding the cellular basis of neurological disorders have advanced at a
      slow pace, especially due to the extreme invasiveness of brain biopsying and
      limitations of cell lines and animal models that have been used. Since the
      derivation of pluripotent stem cells (PSCs), a novel source of cells for
      regenerative medicine and disease modeling has become available, holding great
      potential for the neurology field. However, safety for therapy and accurateness
      for modeling have been a matter of intense debate, considering that genomic
      instability, including the gain and loss of chromosomes (aneuploidy), has been
      repeatedly observed in those cells. Despite the fact that recent reports have
      described some degree of aneuploidy as being normal during neuronal
      differentiation and present in healthy human brains, this phenomenon is
      particularly controversial since it has traditionally been associated with cancer
      and disabling syndromes. It is therefore necessary to appreciate, to which
      extent, aneuploid pluripotent stem cells are suitable for regenerative medicine
      and neurological modeling and also the limits that separate constitutive from
      disease-related aneuploidy. In this review, recent findings regarding chromosomal
      instability in PSCs and within the brain will be discussed.

PMID- 22973196
TI  - Distribution of visual and saccade related information in the monkey inferior
      colliculus.
AB  - The inferior colliculus (IC) is an essential stop early in the ascending auditory
      pathway. Though normally thought of as a predominantly auditory structure, recent
      work has uncovered a variety of non-auditory influences on firing rate in the IC.
      Here, we map the location within the IC of neurons that respond to the onset of a
      fixation-guiding visual stimulus. Visual/visuomotor associated activity was found
      throughout the IC (overall, 84 of 199 sites tested or 42%), but with a far
      reduced prevalence and strength along recording penetrations passing through the
      tonotopically organized region of the IC, putatively the central nucleus (11 of
      42 sites tested, or 26%). These results suggest that visual information has only
      a weak effect on early auditory processing in core regions, but more strongly
      targets the modulatory shell regions of the IC.

PMID- 22973197
TI  - Exact distinction of excitatory and inhibitory neurons in neural networks: a
      study with GFP-GAD67 neurons optically and electrophysiologically recognized on
      multielectrode arrays.
AB  - Distinguishing excitatory from inhibitory neurons with multielectrode array (MEA)
      recordings is a serious experimental challenge. The current methods, developed in
      vitro, mostly rely on spike waveform analysis. These however often display poor
      resolution and may produce errors caused by the variability of spike amplitudes
      and neuron shapes. Recent recordings in human brain suggest that the spike
      waveform features correlate with time-domain statistics such as spiking rate,
      autocorrelation, and coefficient of variation. However, no precise criteria are
      available to exactly assign identified units to specific neuronal types, either
      in vivo or in vitro. To solve this problem, we combined MEA recording with
      fluorescence imaging of neocortical cultures from mice expressing green
      fluorescent protein (GFP) in GABAergic cells. In this way, we could sort out
      "authentic excitatory neurons" (AENs) and "authentic inhibitory neurons" (AINs).
      We thus characterized 1275 units (from 405 electrodes, n = 10 experiments), based
      on autocorrelation, burst length, spike number (SN), spiking rate, squared
      coefficient of variation, and Fano factor (FF) (the ratio between spike-count
      variance and mean). These metrics differed by about one order of magnitude
      between AINs and AENs. In particular, the FF turned out to provide a firing code
      which exactly (no overlap) recognizes excitatory and inhibitory units. The
      difference in FF between all of the identified AEN and AIN groups was highly
      significant (p < 10(-8), ANOVA post-hoc Tukey test). Our results indicate a
      statistical metric-based approach to distinguish excitatory from inhibitory
      neurons independently from the spike width.

PMID- 22973195
TI  - From behavioral context to receptors: serotonergic modulatory pathways in the IC.
AB  - In addition to ascending, descending, and lateral auditory projections, inputs
      extrinsic to the auditory system also influence neural processing in the inferior
      colliculus (IC). These types of inputs often have an important role in signaling
      salient factors such as behavioral context or internal state. One route for such
      extrinsic information is through centralized neuromodulatory networks like the
      serotonergic system. Serotonergic inputs to the IC originate from centralized
      raphe nuclei, release serotonin in the IC, and activate serotonin receptors
      expressed by auditory neurons. Different types of serotonin receptors act as
      parallel pathways regulating specific features of circuitry within the IC. This
      results from variation in subcellular localizations and effector pathways of
      different receptors, which consequently influence auditory responses in distinct
      ways. Serotonin receptors may regulate GABAergic inhibition, influence response
      gain, alter spike timing, or have effects that are dependent on the level of
      activity. Serotonin receptor types additionally interact in nonadditive ways to
      produce distinct combinatorial effects. This array of effects of serotonin is
      likely to depend on behavioral context, since the levels of serotonin in the IC
      transiently increase during behavioral events including stressful situations and
      social interaction. These studies support a broad model of serotonin receptors as
      a link between behavioral context and reconfiguration of circuitry in the IC, and
      the resulting possibility that plasticity at the level of specific receptor types
      could alter the relationship between context and circuit function.

PMID- 22973198
TI  - A compact and realistic cerebral cortical layout derived from prewhitened resting
      state fMRI time series: Cherniak's adjacency rule, size law, and metamodule
      grouping upheld.
AB  - We used hierarchical tree clustering to derive a functional organizational chart
      of 52 human cortical areas (26 per hemisphere) from zero-lag correlations
      calculated between single-voxel, prewhitened, resting-state BOLD fMRI time series
      in 18 subjects. No special "resting-state networks" were identified. There were
      four major features in the resulting tree (dendrogram). First, there was a strong
      clustering of homotopic, left-right hemispheric areas. Second, cortical areas
      were concatenated in multiple, partially overlapping clusters. Third, the
      arrangement of the areas revealed a layout that closely resembled the actual
      layout of the cerebral cortex, namely an orderly progression from anterior to
      posterior. And fourth, the layout of the cortical areas in the tree conformed to
      principles of efficient, compact layout of components proposed by Cherniak. Since
      the tree was derived on the basis of the strength of neural correlations, these
      results document an orderly relation between functional interactions and layout,
      i.e., between structure and function.

PMID- 22973199
TI  - The fuzzy brain. Vagueness and mapping connectivity of the human cerebral cortex.
AB  - While the past century of neuroscientific research has brought considerable
      progress in defining the boundaries of the human cerebral cortex, there are cases
      in which the demarcation of one area from another remains fuzzy. Despite the
      existence of clearly demarcated areas, examples of gradual transitions between
      areas are known since early cytoarchitectonic studies. Since multi-modal
      anatomical approaches and functional connectivity studies brought renewed
      attention to the topic, a better understanding of the theoretical and
      methodological implications of fuzzy boundaries in brain science can be
      conceptually useful. This article provides a preliminary conceptual framework to
      understand this problem by applying philosophical theories of vagueness to three
      levels of neuroanatomical research. For the first two levels (cytoarchitectonics
      and fMRI studies), vagueness will be distinguished from other forms of
      uncertainty, such as imprecise measurement or ambiguous causal sources of
      activation. The article proceeds to discuss the implications of these levels for
      the anatomical study of connectivity between cortical areas. There, vagueness
      gets imported into connectivity studies since the network structure is dependent
      on the parcellation scheme and thresholds have to be used to delineate functional
      boundaries. Functional connectivity may introduce an additional form of
      vagueness, as it is an organizational principle of the brain. The article
      concludes by discussing what steps are appropriate to define areal boundaries
      more precisely.

PMID- 22973200
TI  - The ADHD-200 Consortium: A Model to Advance the Translational Potential of
      Neuroimaging in Clinical Neuroscience.

PMID- 22973201
TI  - Auditory map reorganization and pitch discrimination in adult rats chronically
      exposed to low-level ambient noise.
AB  - Behavioral adaption to a changing environment is critical for an animal's
      survival. How well the brain can modify its functional properties based on
      experience essentially defines the limits of behavioral adaptation. In adult
      animals the extent to which experience shapes brain function has not been fully
      explored. Moreover, the perceptual consequences of experience-induced changes in
      the brains of adults remain unknown. Here we show that the tonotopic map in the
      primary auditory cortex of adult rats living with low-level ambient noise
      underwent a dramatic reorganization. Behaviorally, chronic noise-exposure
      impaired fine, but not coarse pitch discrimination. When tested in a noisy
      environment, the noise-exposed rats performed as well as in a quiet environment
      whereas the control rats performed poorly. This suggests that noise-exposed
      animals had adapted to living in a noisy environment. Behavioral pattern analyses
      revealed that stress or distraction engendered by the noisy background could not
      account for the poor performance of the control rats in a noisy environment. A
      reorganized auditory map may therefore have served as the neural substrate for
      the consistent performance of the noise-exposed rats in a noisy environment.

PMID- 22973202
TI  - Coding of multisensory temporal patterns in human superior temporal sulcus.
AB  - Philosophers, psychologists, and neuroscientists have long been interested in how
      the temporal aspects of perception are represented in the brain. In the present
      study, we investigated the neural basis of the temporal perception of
      synchrony/asynchrony for audiovisual speech stimuli using functional magnetic
      resonance imaging (fMRI). Subjects judged the temporal relation of (a)synchronous
      audiovisual speech streams, and indicated any changes in their perception of the
      stimuli over time. Differential hemodynamic responses for synchronous versus
      asynchronous stimuli were observed in the multisensory superior temporal sulcus
      complex (mSTS-c) and prefrontal cortex. Within mSTS-c we found adjacent regions
      expressing an enhanced BOLD-response to the different physical (a)synchrony
      conditions. These regions were further modulated by the subjects' perceptual
      state. By calculating the distances between the modulated regions within mSTS-c
      in single-subjects we demonstrate that the "auditory leading (A(L))" and "visual
      leading (V(L)) areas" lie closer to "synchrony areas" than to each other.
      Moreover, analysis of interregional connectivity indicates a stronger functional
      connection between multisensory prefrontal cortex and mSTS-c during the
      perception of asynchrony. Taken together, these results therefore suggest the
      presence of distinct sub-regions within the human STS-c for the maintenance of
      temporal relations for audiovisual speech stimuli plus differential functional
      connectivity with prefrontal regions. The respective local activity in mSTS-c is
      dependent both upon the physical properties of the stimuli presented and upon the
      subjects' perception of (a)synchrony.

PMID- 22973204
TI  - Capture of visual attention interferes with multisensory speech processing.
AB  - Attending to a conversation in a crowded scene requires selection of relevant
      information, while ignoring other distracting sensory input, such as speech
      signals from surrounding people. The neural mechanisms of how distracting stimuli
      influence the processing of attended speech are not well understood. In this high
      density electroencephalography (EEG) study, we investigated how different types
      of speech and non-speech stimuli influence the processing of attended audiovisual
      speech. Participants were presented with three horizontally aligned speakers who
      produced syllables. The faces of the three speakers flickered at specific
      frequencies (19 Hz for flanking speakers and 25 Hz for the center speaker), which
      induced steady-state visual evoked potentials (SSVEP) in the EEG that served as a
      measure of visual attention. The participants' task was to detect an occasional
      audiovisual target syllable produced by the center speaker, while ignoring
      distracting signals originating from the two flanking speakers. In all
      experimental conditions the center speaker produced a bimodal audiovisual
      syllable. In three distraction conditions, which were contrasted with a no
      distraction control condition, the flanking speakers either produced audiovisual
      speech, moved their lips, and produced acoustic noise, or moved their lips
      without producing an auditory signal. We observed behavioral interference in the
      reaction times (RTs) in particular when the flanking speakers produced
      naturalistic audiovisual speech. These effects were paralleled by enhanced 19 Hz
      SSVEP, indicative of a stimulus-driven capture of attention toward the
      interfering speakers. Our study provides evidence that non-relevant audiovisual
      speech signals serve as highly salient distractors, which capture attention in a
      stimulus-driven fashion.

PMID- 22973203
TI  - Time-dependent effects of cortisol on selective attention and emotional
      interference: a functional MRI study.
AB  - Acute stress is known to induce a state of hypervigilance, allowing optimal
      detection of threats. Although one may benefit from sensitive sensory processing,
      it comes at the cost of unselective attention and increased distraction by
      irrelevant information. Corticosteroids, released in response to stress, have
      been shown to profoundly influence brain function in a time-dependent manner,
      causing rapid non-genomic and slow genomic effects. Here, we investigated how
      these time-dependent effects influence the neural mechanisms underlying selective
      attention and the inhibition of emotional distracters in humans. Implementing a
      randomized, double-blind, placebo-controlled design, 65 young healthy men
      received 10 mg hydrocortisone either 60 min (rapid effects) or 270 min (slow
      effects), or placebo prior to an emotional distraction task, consisting of color
      naming of either neutral or aversive words. Overall, participants responded
      slower to aversive compared to neutral words, indicating emotional interference
      with selective attention. Importantly, the rapid effects of corticosteroids
      increased emotional interference, which was associated with reduced amygdala
      inhibition to aversive words. Moreover, they induced enhanced amygdala
      connectivity with frontoparietal brain regions, which may reflect increased
      influence of the amygdala on an executive network. The slow effects of
      corticosteroids acted on the neural correlates of sustained attention. They
      decreased overall activity in the cuneus, possibly indicating reduced bottom-up
      attentional processing, and disrupted amygdala connectivity to the insula,
      potentially reducing emotional interference. Altogether, these data suggest a
      time-specific corticosteroid modulation of attentive processing. Whereas high
      circulating corticosteroid levels acutely increase emotional interference,
      possibly facilitating the detection of threats, a history of elevation might
      promote sustained attention and thereby contribute to stress-recovery of
      cognitive function.

PMID- 22973205
TI  - Willed action, free will, and the stochastic neurodynamics of decision-making.
AB  - It is shown that the randomness of the firing times of neurons in decision-making
      attractor neuronal networks that is present before the decision cues are applied
      can cause statistical fluctuations that influence the decision that will be
      taken. In this rigorous sense, it is possible to partially predict decisions
      before they are made. This raises issues about free will and determinism. There
      are many decision-making networks in the brain. Some decision systems operate to
      choose between gene-specified rewards such as taste, touch, and beauty (in for
      example the peacock's tail). Other processes capable of planning ahead with
      multiple steps held in working memory may require correction by higher order
      thoughts that may involve explicit, conscious, processing. The explicit system
      can allow the gene-specified rewards not to be selected or deferred. The
      decisions between the selfish gene-specified rewards, and the explicitly
      calculated rewards that are in the interests of the individual, the phenotype,
      may themselves be influenced by noise in the brain. When the explicit planning
      system does take the decision, it can report on its decision-making, and can
      provide a causal account rather than a confabulation about the decision process.
      We might use the terms "willed action" and "free will" to refer to the operation
      of the planning system that can think ahead over several steps held in working
      memory with which it can take explicit decisions. Reduced connectivity in some of
      the default mode cortical regions including the precuneus that are active during
      self-initiated action appears to be related to the reduction in the sense of self
      and agency, of causing willed actions, that can be present in schizophrenia.

PMID- 22973207
TI  - The influence of affective states varying in motivational intensity on cognitive
      scope.
AB  - We review a program of research that has suggested that affective states high in
      motivationally intensity (e.g., enthusiasm, disgust) narrow cognitive scope,
      whereas affective states low in motivationally intensity (e.g., joy, sadness)
      broaden cognitive scope. Further supporting this interpretation, indices of brain
      activations, derived from human electroencephalography, suggest that the
      motivational intensity of the affective state predicts the narrowing of cognitive
      scope. Finally, research suggests that the relationship between emotive intensity
      and cognitive scope is bi-directional, such that manipulated changes in cognitive
      scope influence early brain activations associated with emotive intensity. In the
      end, the review highlights how emotion can impair and improve certain cognitive
      processes.

PMID- 22973206
TI  - Response inhibition signals and miscoding of direction in dorsomedial striatum.
AB  - The ability to inhibit action is critical for everyday behavior and is affected
      by a variety of disorders. Behavioral control and response inhibition is thought
      to depend on a neural circuit that includes the dorsal striatum, yet the neural
      signals that lead to response inhibition and its failure are unclear. To address
      this issue, we recorded from neurons in rat dorsomedial striatum (mDS) in a novel
      task in which rats responded to a spatial cue that signaled that reward would be
      delivered either to the left or to the right. On 80% of trials rats were
      instructed to respond in the direction cued by the light (GO). On 20% of trials a
      second light illuminated instructing the rat to refrain from making the cued
      movement and move in the opposite direction (STOP). Many neurons in mDS encoded
      direction, firing more or less strongly for GO movements made ipsilateral or
      contralateral to the recording electrode. Neurons that fired more strongly for
      contralateral GO responses were more active when rats were faster, showed reduced
      activity on STOP trials, and miscoded direction on errors, suggesting that when
      these neurons were overly active, response inhibition failed. Neurons that
      decreased firing for contralateral movement were excited during trials in which
      the rat was required to stop the ipsilateral movement. For these neurons activity
      was reduced when errors were made and was negatively correlated with movement
      time suggesting that when these neurons were less active on STOP trials, response
      inhibition failed. Finally, the activity of a significant number of neurons
      represented a global inhibitory signal, firing more strongly during response
      inhibition regardless of response direction. Breakdown by cell type suggests that
      putative medium spiny neurons (MSNs) tended to fire more strongly under STOP
      trials, whereas putative interneurons exhibited both activity patterns.

PMID- 22973208
TI  - The effect of task order predictability in audio-visual dual task performance:
      Just a central capacity limitation?
AB  - In classic Psychological-Refractory-Period (PRP) dual-task paradigms, decreasing
      stimulus onset asynchronies (SOA) between the two tasks typically lead to
      increasing reaction times (RT) to the second task and, when task order is non
      predictable, to prolonged RTs to the first task. Traditionally, both RT effects
      have been advocated to originate exclusively from the dynamics of a central
      bottleneck. By focusing on two specific electroencephalographic brain responses
      directly linkable to perceptual or motor processing stages, respectively, the
      present study aimed to provide a more detailed picture as to the origin(s) of
      these behavioral PRP effects. In particular, we employed 2-alternative forced
      choice (2AFC) tasks requiring participants to identify the pitch of a tone (high
      versus low) in the auditory, and the orientation of a target object (vertical
      versus horizontal) in the visual, task, with task order being either predictable
      or non-predictable. Our findings show that task order predictability (TOP) and
      inter-task SOA interactively determine the speed of (visual) perceptual processes
      (as indexed by the PCN timing) for both the first and the second task. By
      contrast, motor response execution times (as indexed by the LRP timing) are
      influenced independently by TOP for the first, and SOA for the second, task.
      Overall, this set of findings complements classical as well as advanced versions
      of the central bottleneck model by providing electrophysiological evidence for
      modulations of both perceptual and motor processing dynamics that, in summation
      with central capacity limitations, give rise to the behavioral PRP outcome.

PMID- 22973209
TI  - Pro-cognitive drug effects modulate functional brain network organization.
AB  - Previous studies document that cholinergic and noradrenergic drugs improve
      attention, memory and cognitive control in healthy subjects and patients with
      neuropsychiatric disorders. In humans neural mechanisms of cholinergic and
      noradrenergic modulation have mainly been analyzed by investigating drug-induced
      changes of task-related neural activity measured with functional magnetic
      resonance imaging (fMRI). Endogenous neural activity has often been neglected.
      Further, although drugs affect the coupling between neurons, only a few human
      studies have explicitly addressed how drugs modulate the functional connectome,
      i.e., the functional neural interactions within the brain. These studies have
      mainly focused on synchronization or correlation of brain activations. Recently,
      there are some drug studies using graph theory and other new mathematical
      approaches to model the brain as a complex network of interconnected processing
      nodes. Using such measures it is possible to detect not only focal, but also
      subtle, widely distributed drug effects on functional network topology. Most
      important, graph theoretical measures also quantify whether drug-induced changes
      in topology or network organization facilitate or hinder information processing.
      Several studies could show that functional brain integration is highly correlated
      with behavioral performance suggesting that cholinergic and noradrenergic drugs
      which improve measures of cognitive performance should increase functional
      network integration. The purpose of this paper is to show that graph theory
      provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive
      drug effects, and also to discuss how these approaches can contribute to the
      understanding of the role of cholinergic and noradrenergic modulation in the
      human brain. Finally we discuss the "global workspace" theory as a theoretical
      framework of pro-cognitive drug effects and argue that pro-cognitive effects of
      cholinergic and noradrenergic drugs might be related to higher network
      integration.

PMID- 22973210
TI  - Perception of biological motion in visual agnosia.
AB  - Over the past 25 years, visual processing has been discussed in the context of
      the dual stream hypothesis consisting of a ventral ("what") and a dorsal
      ("where") visual information processing pathway. Patients with brain damage of
      the ventral pathway typically present with signs of visual agnosia, the inability
      to identify and discriminate objects by visual exploration, but show normal
      perception of motion perception. A dissociation between the perception of
      biological motion and non-biological motion has been suggested: perception of
      biological motion might be impaired when "non-biological" motion perception is
      intact and vice versa. The impact of object recognition on the perception of
      biological motion remains unclear. We thus investigated this question in a
      patient with severe visual agnosia, who showed normal perception of non
      biological motion. The data suggested that the patient's perception of biological
      motion remained largely intact. However, when tested with objects constructed of
      coherently moving dots ("Shape-from-Motion"), recognition was severely impaired.
      The results are discussed in the context of possible mechanisms of biological
      motion perception.

PMID- 22973211
TI  - Social learning in insects: a higher-order capacity?

PMID- 22973212
TI  - Blocking muscarinic receptors in the olfactory bulb impairs performance on an
      olfactory short-term memory task.
AB  - Cholinergic inputs to cortical processing networks have long been associated with
      attentional and top-down processing. Experimental and theoretical studies suggest
      that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural
      and behavioral odor discrimination. Previous experiments from our laboratory and
      others demonstrate that blockade of nicotinic receptors directly impairs
      olfactory discrimination, whereas blockade of muscarinic receptors only
      measurably impairs olfactory perception when task demands are made more
      challenging, such as when very low-concentration odors are used or rats are
      required to maintain sensory memory over long durations. To further investigate
      the role of muscarinic signaling in the OB, we developed an olfactory delayed
      match-to-sample task using a digging-based behavioral paradigm. We find that rats
      are able to maintain robust short-term odor memory for 10-100 s. To investigate
      the role of muscarinic signaling in task performance, we bilaterally infused
      scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair
      performance on the task across all delays tested, including the baseline
      condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no
      measureable effects. These results indicate that general execution of the match
      to-sample task, even with no delay, is at least partially dependent on muscarinic
      signaling in the OB.

PMID- 22973213
TI  - Behavioral characterization of mice lacking Trek channels.
AB  - Two-pore domain K(+) (K(2P)) channels are thought to underlie background K(+)
      conductance in many cell types. The Trek subfamily of K(2P) channels consists of
      three members, Trek1/Kcnk2, Trek2/Kcnk10, and Traak/Kcnk4, all three of which are
      expressed in the rodent CNS. Constitutive ablation of the Trek1 gene in mice
      correlates with enhanced sensitivity to ischemia and epilepsy, decreased
      sensitivity to the effects of inhaled anesthetics, increased sensitivity to
      thermal and mechanical pain, and resistance to depression. While the distribution
      of Trek2 mRNA in the CNS is broad, little is known about the relevance of this
      Trek family member to neurobiology and behavior. Here, we probed the effect of
      constitutive Trek2 ablation, as well as the simultaneous constitutive ablation of
      all three Trek family genes, in paradigms that assess motor activity,
      coordination, anxiety-related behavior, learning and memory, and drug-induced
      reward-related behavior. No differences were observed between Trek2(-/-) and
      Trek1/2/Traak(-/-) mice in coordination or total distance traveled in an open
      field. A gender-dependent impact of Trek ablation on open-field anxiety-related
      behavior was observed, as female but not male Trek2(-/-) and Trek1/2/Traak(-/-)
      mice spent more time in, and made a greater number of entries into, the center of
      the open-field than wild-type counterparts. Further evaluation of anxiety-related
      behavior in the elevated plus maze and light/dark box, however, did not reveal a
      significant influence of genotype on performance for either gender. Furthermore,
      Trek(-/-) mice behaved normally in tests of learning and memory, including
      contextual fear conditioning and novel object recognition, and with respect to
      opioid-induced motor stimulation and conditioned place preference (CPP).
      Collectively, these data argue that despite their broad distribution in the CNS,
      Trek channels exert a minimal influence on a wide-range of behaviors.

PMID- 22973214
TI  - Imagining is Not Doing but Involves Specific Motor Commands: A Review of
      Experimental Data Related to Motor Inhibition.
AB  - There is now compelling evidence that motor imagery (MI) and actual movement
      share common neural substrate. However, the question of how MI inhibits the
      transmission of motor commands into the efferent pathways in order to prevent any
      movement is largely unresolved. Similarly, little is known about the nature of
      the electromyographic activity that is apparent during MI. In addressing these
      gaps in the literature, the present paper argues that MI includes motor execution
      commands for muscle contractions which are blocked at some level of the motor
      system by inhibitory mechanisms. We first assemble data from neuroimaging studies
      that demonstrate that the neural networks mediating MI and motor performance are
      not totally overlapping, thereby highlighting potential differences between MI
      and actual motor execution. We then review MI data indicating the presence of
      subliminal muscular activity reflecting the intrinsic characteristics of the
      motor command as well as increased corticomotor excitability. The third section
      not only considers the inhibitory mechanisms involved during MI but also examines
      how the brain resolves the problem of issuing the motor command for action while
      supervising motor inhibition when people engage in voluntary movement during MI.
      The last part of the paper draws on imagery research in clinical contexts to
      suggest that some patients move while imagining an action, although they are not
      aware of such movements. In particular, experimental data from amputees as well
      as from patients with Parkinson's disease are discussed. We also review recent
      studies based on comparing brain activity in tetraplegic patients with that from
      healthy matched controls that provide insights into inhibitory processes during
      MI. We conclude by arguing that based on available evidence, a multifactorial
      explanation of motor inhibition during MI is warranted.

PMID- 22973215
TI  - "Doctor" or "darling"? Decoding the communication partner from ECoG of the
      anterior temporal lobe during non-experimental, real-life social interaction.
AB  - Human brain processes underlying real-life social interaction in everyday
      situations have been difficult to study and have, until now, remained largely
      unknown. Here, we investigated whether electrocorticography (ECoG) recorded for
      pre-neurosurgical diagnostics during the daily hospital life of epilepsy patients
      could provide a way to elucidate the neural correlates of non-experimental social
      interaction. We identified time periods in which patients were involved in
      conversations with either their respective life partners (Condition 1; C1) or
      attending physicians (Condition 2; C2). These two conditions can be expected to
      differentially involve subfunctions of social interaction which have been
      associated with activity in the anterior temporal lobe (ATL), including the
      temporal pole (TP). Therefore, we specifically focused on ECoG recordings from
      this brain region and investigated spectral power modulations in the alpha (8-12
      Hz) and theta (3-5 Hz) frequency ranges, which have been previously assumed to
      play an important role in the processing of social interaction. We hypothesized
      that brain activity in this region might be sensitive to differences in the two
      interaction situations and tested whether these differences can be detected by
      single-trial decoding. Condition-specific effects in both theta and alpha bands
      were observed: the left and right TP exclusively showed increased power in C1
      compared to C2, whereas more posterior parts of the ATL exhibited similar (C1 >
      C2) and also contrary (C2 > C1) effects. Single-trial decoding accuracies for
      classification of these effects were highly above chance. Our findings
      demonstrate that it is possible to study the neural correlates of human social
      interaction in non-experimental conditions. Decoding the identity of the
      communication partner and adjusting the speech output accordingly may be useful
      in the emerging field of brain-machine interfacing for restoration of expressive
      speech.

PMID- 22973216
TI  - Explicit and implicit issues in the developmental cognitive neuroscience of
      social inequality.
AB  - The appearance of developmental cognitive neuroscience (DCN) in the socioeconomic
      status (SES) research arena is hugely transformative, but challenging. We review
      challenges rooted in the implicit and explicit assumptions informing this newborn
      field. We provide balanced theoretical alternatives on how hypothesized
      psychological processes map onto the brain (e.g., problem of localization) and
      how experimental phenomena at multiple levels of analysis (e.g., behavior,
      cognition and the brain) could be related. We therefore examine unclear issues
      regarding the existing perspectives on poverty and their relationships with low
      SES, the evidence of low-SES adaptive functioning, historical precedents of the
      "alternate pathways" (neuroplasticity) interpretation of learning disabilities
      related to low-SES and the notion of deficit, issues of "normativity" and
      validity in findings of neurocognitive differences between children from
      different SES, and finally alternative interpretations of the complex
      relationship between IQ and SES. Particularly, we examine the extent to which the
      available laboratory results may be interpreted as showing that cognitive
      performance in low-SES children reflects cognitive and behavioral deficits as a
      result of growing up in specific environmental or cultural contexts, and how the
      experimental findings should be interpreted for the design of different types of
      interventions-particularly those related to educational practices-or translated
      to the public-especially the media. Although a cautionary tone permeates many
      studies, still, a potential deficit attribution-i.e., low-SES is associated with
      cognitive and behavioral developmental deficits-seems almost an inevitable
      implicit issue with ethical implications. Finally, we sketch the agenda for an
      ecological DCN, suggesting recommendations to advance the field, specifically, to
      minimize equivocal divulgation and maximize ethically responsible translation.

PMID- 22973217
TI  - Increased prefrontal activity and reduced motor cortex activity during imagined
      eccentric compared to concentric muscle actions.
AB  - In this study we used functional magnetic resonance imaging (fMRI) to examine
      differences in recruited brain regions during the concentric and the eccentric
      phase of an imagined maximum resistance training task of the elbow flexors in
      healthy young subjects. The results showed that during the eccentric phase, pre
      frontal cortex (BA44) bilaterally was recruited when contrasted to the concentric
      phase. During the concentric phase, however, the motor and pre-motor cortex (BA
      4/6) was recruited when contrasted to the eccentric phase. Interestingly, the
      brain activity of this region was reduced, when compared to the mean activity of
      the session, during the eccentric phase. Thus, the neural mechanisms governing
      imagined concentric and eccentric contractions appear to differ. We propose that
      the recruitment of the pre-frontal cortex is due to an increased demand of
      regulating force during the eccentric phase. Moreover, it is possible that the
      inability to fully activate a muscle during eccentric contractions may partly be
      explained by a reduction of activity in the motor and pre-motor cortex.

PMID- 22973218
TI  - Intensive training induces longitudinal changes in meditation state-related EEG
      oscillatory activity.
AB  - The capacity to focus one's attention for an extended period of time can be
      increased through training in contemplative practices. However, the cognitive
      processes engaged during meditation that support trait changes in cognition are
      not well characterized. We conducted a longitudinal wait-list controlled study of
      intensive meditation training. Retreat participants practiced focused attention
      (FA) meditation techniques for three months during an initial retreat. Wait-list
      participants later undertook formally identical training during a second retreat.
      Dense-array scalp-recorded electroencephalogram (EEG) data were collected during
      6 min of mindfulness of breathing meditation at three assessment points during
      each retreat. Second-order blind source separation, along with a novel semi
      automatic artifact removal tool (SMART), was used for data preprocessing. We
      observed replicable reductions in meditative state-related beta-band power
      bilaterally over anteriocentral and posterior scalp regions. In addition,
      individual alpha frequency (IAF) decreased across both retreats and in direct
      relation to the amount of meditative practice. These findings provide evidence
      for replicable longitudinal changes in brain oscillatory activity during
      meditation and increase our understanding of the cortical processes engaged
      during meditation that may support long-term improvements in cognition.

PMID- 22973219
TI  - Beta- and gamma-range human lower limb corticomuscular coherence.
AB  - Coherence between electroencephalography (EEG) recorded on the scalp above the
      motor cortex and electromyography (EMG) recorded on the skin of the limbs is
      thought to reflect corticospinal coupling between motor cortex and muscle motor
      units. Beta-range (13-30 Hz) corticomuscular coherence has been extensively
      documented during static force output while gamma-range (31-45 Hz) coherence has
      been linked to dynamic force output. However, the explanation for this beta-to
      gamma coherence shift remains unclear. We recorded 264-channel EEG and 8-channel
      lower limb EMG while eight healthy subjects performed isometric and isotonic,
      knee, and ankle exercises. Adaptive mixture independent component analysis
      (AMICA) parsed EEG into models of underlying source signals. We computed
      magnitude squared coherence between electrocortical source signals and EMG.
      Significant coherence between contralateral motor cortex electrocortical signals
      and lower limb EMG was observed in the beta- and gamma-range for all exercise
      types. Gamma-range coherence was significantly greater for isotonic exercises
      than for isometric exercises. We conclude that active muscle movement modulates
      the speed of corticospinal oscillations. Specifically, isotonic contractions
      shift corticospinal oscillations toward the gamma-range while isometric
      contractions favor beta-range oscillations. Prior research has suggested that
      tasks requiring increased integration of visual and somatosensory information may
      shift corticomuscular coherence to the gamma-range. The isometric and isotonic
      tasks studied here likely required similar amounts of visual and somatosensory
      integration. This suggests that muscle dynamics, including the amount and type of
      proprioception, may play a role in the beta-to-gamma shift.

PMID- 22973220
TI  - An Approximation to the Adaptive Exponential Integrate-and-Fire Neuron Model
      Allows Fast and Predictive Fitting to Physiological Data.
AB  - For large-scale network simulations, it is often desirable to have
      computationally tractable, yet in a defined sense still physiologically valid
      neuron models. In particular, these models should be able to reproduce
      physiological measurements, ideally in a predictive sense, and under different
      input regimes in which neurons may operate in vivo. Here we present an approach
      to parameter estimation for a simple spiking neuron model mainly based on
      standard f-I curves obtained from in vitro recordings. Such recordings are
      routinely obtained in standard protocols and assess a neuron's response under a
      wide range of mean-input currents. Our fitting procedure makes use of closed-form
      expressions for the firing rate derived from an approximation to the adaptive
      exponential integrate-and-fire (AdEx) model. The resulting fitting process is
      simple and about two orders of magnitude faster compared to methods based on
      numerical integration of the differential equations. We probe this method on
      different cell types recorded from rodent prefrontal cortex. After fitting to the
      f-I current-clamp data, the model cells are tested on completely different sets
      of recordings obtained by fluctuating ("in vivo-like") input currents. For a wide
      range of different input regimes, cell types, and cortical layers, the model
      could predict spike times on these test traces quite accurately within the bounds
      of physiological reliability, although no information from these distinct test
      sets was used for model fitting. Further analyses delineated some of the
      empirical factors constraining model fitting and the model's generalization
      performance. An even simpler adaptive LIF neuron was also examined in this
      context. Hence, we have developed a "high-throughput" model fitting procedure
      which is simple and fast, with good prediction performance, and which relies only
      on firing rate information and standard physiological data widely and easily
      available.

PMID- 22973221
TI  - Synaptic depression and slow oscillatory activity in a biophysical network model
      of the cerebral cortex.
AB  - Short-term synaptic depression (STD) is a form of synaptic plasticity that has a
      large impact on network computations. Experimental results suggest that STD is
      modulated by cortical activity, decreasing with activity in the network and
      increasing during silent states. Here, we explored different activity-modulation
      protocols in a biophysical network model for which the model displayed less STD
      when the network was active than when it was silent, in agreement with
      experimental results. Furthermore, we studied how trains of synaptic potentials
      had lesser decay during periods of activity (UP states) than during silent
      periods (DOWN states), providing new experimental predictions. We next tackled
      the inverse question of what is the impact of modifying STD parameters on the
      emergent activity of the network, a question difficult to answer experimentally.
      We found that synaptic depression of cortical connections had a critical role to
      determine the regime of rhythmic cortical activity. While low STD resulted in an
      emergent rhythmic activity with short UP states and long DOWN states, increasing
      STD resulted in longer and more frequent UP states interleaved with short silent
      periods. A still higher synaptic depression set the network into a non
      oscillatory firing regime where DOWN states no longer occurred. The speed of
      propagation of UP states along the network was not found to be modulated by STD
      during the oscillatory regime; it remained relatively stable over a range of
      values of STD. Overall, we found that the mutual interactions between synaptic
      depression and ongoing network activity are critical to determine the mechanisms
      that modulate cortical emergent patterns.

PMID- 22973223
TI  - A computational role for bistability and traveling waves in motor cortex.
AB  - Adaptive changes in behavior require rapid changes in brain states yet the brain
      must also remain stable. We investigated two neural mechanisms for evoking rapid
      transitions between spatiotemporal synchronization patterns of beta oscillations
      (13-30 Hz) in motor cortex. Cortex was modeled as a sheet of neural oscillators
      that were spatially coupled using a center-surround connection topology.
      Manipulating the inhibitory surround was found to evoke reliable transitions
      between synchronous oscillation patterns and traveling waves. These transitions
      modulated the simulated local field potential in agreement with physiological
      observations in humans. Intermediate levels of surround inhibition were also
      found to produce bistable coupling topologies that supported both waves and
      synchrony. State-dependent perturbation between bistable states produced very
      rapid transitions but were less reliable. We surmise that motor cortex may thus
      employ state-dependent computation to achieve very rapid changes between bistable
      motor states when the demand for speed exceeds the demand for accuracy.

PMID- 22973224
TI  - Automated regional behavioral analysis for human brain images.
AB  - Behavioral categories of functional imaging experiments along with standardized
      brain coordinates of associated activations were used to develop a method to
      automate regional behavioral analysis of human brain images. Behavioral and
      coordinate data were taken from the BrainMap database (http://www.brainmap.org/),
      which documents over 20 years of published functional brain imaging studies. A
      brain region of interest (ROI) for behavioral analysis can be defined in
      functional images, anatomical images or brain atlases, if images are spatially
      normalized to MNI or Talairach standards. Results of behavioral analysis are
      presented for each of BrainMap's 51 behavioral sub-domains spanning five
      behavioral domains (Action, Cognition, Emotion, Interoception, and Perception).
      For each behavioral sub-domain the fraction of coordinates falling within the ROI
      was computed and compared with the fraction expected if coordinates for the
      behavior were not clustered, i.e., uniformly distributed. When the difference
      between these fractions is large behavioral association is indicated. A z-score
      >= 3.0 was used to designate statistically significant behavioral association.
      The left-right symmetry of ~100K activation foci was evaluated by hemisphere,
      lobe, and by behavioral sub-domain. Results highlighted the classic left-side
      dominance for language while asymmetry for most sub-domains (~75%) was not
      statistically significant. Use scenarios were presented for anatomical ROIs from
      the Harvard-Oxford cortical (HOC) brain atlas, functional ROIs from statistical
      parametric maps in a TMS-PET study, a task-based fMRI study, and ROIs from the
      ten "major representative" functional networks in a previously published resting
      state fMRI study. Statistically significant behavioral findings for these use
      scenarios were consistent with published behaviors for associated anatomical and
      functional regions.

PMID- 22973222
TI  - Astrocyte regulation of sleep circuits: experimental and modeling perspectives.
AB  - Integrated within neural circuits, astrocytes have recently been shown to
      modulate brain rhythms thought to mediate sleep function. Experimental evidence
      suggests that local impact of astrocytes on single synapses translates into
      global modulation of neuronal networks and behavior. We discuss these findings in
      the context of current conceptual models of sleep generation and function, each
      of which have historically focused on neural mechanisms. We highlight the
      implications and the challenges introduced by these results from a conceptual and
      computational perspective. We further provide modeling directions on how these
      data might extend our knowledge of astrocytic properties and sleep function.
      Given our evolving understanding of how local cellular activities during sleep
      lead to functional outcomes for the brain, further mechanistic and theoretical
      understanding of astrocytic contribution to these dynamics will undoubtedly be of
      great basic and translational benefit.

PMID- 22973225
TI  - Volitional inhibition and brain-machine interfaces: a mandatory wedding.

PMID- 22973226
TI  - Lung function measurements in rodents in safety pharmacology studies.
AB  - The ICH guideline S7A requires safety pharmacology tests including measurements
      of pulmonary function. In the first step - as part of the "core battery" - lung
      function tests in conscious animals are requested. If potential adverse effects
      raise concern for human safety, these should be explored in a second step as a
      "follow-up study." For these two stages of safety pharmacology testing, both non
      invasive and invasive techniques are needed which should be as precise and
      reliable as possible. A short overview of typical in vivo measurement techniques
      is given, their advantages and disadvantages are discussed and out of these the
      non-invasive head-out body plethysmography and the invasive but repeatable body
      plethysmography in orotracheally intubated rodents are presented in detail. For
      validation purposes the changes in the respective parameters such as tidal
      midexpiratory flow (EF(50)) or lung resistance have been recorded in the same
      animals in typical bronchoconstriction models and compared. In addition, the
      technique of head-out body plethysmography has been shown to be useful to measure
      lung function in juvenile rats starting from day two of age. This allows safety
      pharmacology testing and toxicological studies in juvenile animals as a model for
      the young developing organism as requested by the regulatory authorities (e.g.,
      EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive
      pulmonary function tests are capable of detecting effects and alterations on the
      respiratory system with different selectivity and area of operation. The use of
      both techniques in a large number of studies in mice and rats in the last years
      have demonstrated that they provide useful and reliable information on pulmonary
      mechanics in safety pharmacology and toxicology testing, in investigations of
      respiratory disorders, and in pharmacological efficacy studies.

PMID- 22973227
TI  - Development of CFTR Structure.
AB  - Cystic fibrosis is a lethal genetic disease caused by lack of functional cystic
      fibrosis transmembrane conductance regulator (CFTR) proteins at the apical
      surface of secretory epithelia. CFTR is a multidomain protein, containing five
      domains, and its functional structure is attained in a hierarchical folding
      process. Most CF-causing mutations in CFTR, including the most common mutation, a
      deletion of phenylalanine at position 508 (DeltaF508), are unable to properly
      fold into this functional native three dimensional structure. Currently, no high
      resolution structural information about full length CFTR exists. However, insight
      has been gained through examining homologous ABC transporter structures,
      molecular modeling, and high-resolution structures of individual, isolated CFTR
      domains. Taken together, these studies indicate that the prevalent DeltaF508
      mutation disrupts two essential steps during the development of the native
      structure: folding of the first nucleotide binding domain (NBD1) and its later
      association with the fourth intracellular loop (ICL4) in the second transmembrane
      domain (TMD2). Therapeutics to rescue DeltaF508 and other mutants in CFTR can be
      targeted to correct defects that occur during the complex folding process. This
      article reviews the structural relationships between CFTR and ABC transporters
      and current knowledge about how CFTR attains its structure-with a focus on how
      this process is altered by CF-causing mutations in a manner targetable by
      therapeutics.

PMID- 22973228
TI  - Polyunsaturated Fatty acids modify the gating of kv channels.
AB  - Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic
      properties, which are attributed to their capability to modulate ion channels.
      This PUFAs ability has been reported to be due to their effects on the gating
      properties of ion channels. In the present review, we will focus on the role of
      PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are
      blocked by n-3 PUFAs of marine [docosahexaenoic acid (DHA) and eicosapentaenoic
      acid] and plant origin (alpha-linolenic acid, ALA) at physiological
      concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the
      range of membrane potentials coinciding with those of Kv1.5 channel activation,
      suggesting that PUFAs-channel binding may derive a significant fraction of its
      voltage sensitivity through the coupling to channel gating. A similar shift in
      the activation voltage was noted for the effects of n-6 arachidonic acid (AA) and
      DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time
      dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5
      channel opening is a prerequisite for the PUFA-channel interaction. Similar to
      the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply
      increased in the range of membrane potentials that coincided with the range of
      Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are
      also coupled to channel gating. Furthermore, AA regulates the inactivation
      process in other Kv channels, introducing a fast voltage-dependent inactivation
      in non-inactivating Kv channels. These results have been explained within the
      framework that AA closes voltage-dependent potassium channels by inducing
      conformational changes in the selectivity filter, suggesting that Kv channel
      gating is lipid dependent.

PMID- 22973229
TI  - The MET Oncogene as a Therapeutical Target in Cancer Invasive Growth.
AB  - The MET proto-oncogene, encoding the tyrosine kinase receptor for Hepatocyte
      Growth Factor (HGF) regulates invasive growth, a genetic program that associates
      control of cell proliferation with invasion of the extracellular matrix and
      protection from apoptosis. Physiologically, invasive growth takes place during
      embryonic development, and, in post-natal life, in wound healing and regeneration
      of several tissues. The MET oncogene is overexpressed and/or genetically mutated
      in many tumors, thereby sustaining pathological invasive growth, a prerequisite
      for metastasis. MET is the subject of intense research as a target for small
      molecule kinase inhibitors and, together with its ligand HGF, for inhibitory
      antibodies. The tight interplay of MET with the protease network has unveiled
      mechanisms to be exploited to achieve effective inhibition of invasive growth.

PMID- 22973230
TI  - Prediction of outcome and selection of the liver transplantat candidate in acute
      liver failure.
AB  - Acute liver failure (ALF) is characterized by a sudden and severe deterioration
      of liver function, typically mirrored by a marked increase of the international
      normalized ratio (INR) and hepatic encephalopathy (HE). Due to various possible
      causes hepatocytes get damaged via either apoptotic or necrotic pathways.
      Anticipating the natural prognosis of a patient with ALF is one of the most
      challenging tasks in hepatology critical care. Important factors that influence
      the chance of spontaneous recovery are the underlying etiology of acute liver
      failure, the acuity of disease, and the severity of HE. Once an estimation of the
      prognosis in the individual patient has been made, this quickly has to be
      integrated in the discussion whether high-urgency liver transplantation is
      necessary and justifiable. This decision has to cover several medical, social,
      and organizational issues. Well organized liver transplantation programs around
      the world have achieved an impressive improvement of the 1 year survival rate in
      ALF from around 40% without transplantation up to nearly 80% with
      transplantation. The recent debate on whether severe acute alcoholic hepatitis
      could represent a new candidate eligible for high-urgency liver transplantation
      shows that the topic is still open for discussion.

PMID- 22973231
TI  - betaENaC is a molecular component of a VSMC mechanotransducer that contributes to
      renal blood flow regulation, protection from renal injury, and hypertension.
AB  - Pressure-induced constriction (also known as the "myogenic response") is an
      important mechano-dependent response in certain blood vessels. The response is
      mediated by vascular smooth muscle cells (VSMCs) and characterized by a pressure
      induced vasoconstriction in small arteries and arterioles in the cerebral,
      mesenteric, cardiac, and renal beds. The myogenic response has two important
      roles; it is a mechanism of blood flow autoregulation and provides protection
      against systemic blood pressure-induced damage to delicate microvessels. However,
      the molecular mechanism(s) underlying initiation of myogenic response is unclear.
      Degenerin proteins have a strong evolutionary link to mechanotransduction in the
      nematode. Our laboratory has addressed the hypothesis that these proteins may
      also act as mechanosensors in certain mammalian tissues such as VSMCs and
      arterial baroreceptor neurons. This article discusses the importance of a
      specific degenerin protein, beta Epithelial Na(+) Channel (betaENaC) in pressure
      induced vasoconstriction in renal vessels and arterial baroreflex function as
      determined in a mouse model of reduced betaENaC (betaENaC m/m). We propose that
      loss of baroreflex sensitivity (due to loss of baroreceptor betaENaC) increases
      blood pressure variability, increasing the likelihood and magnitude of upward
      swings in systemic pressure. Furthermore, loss of the myogenic constrictor
      response (due to loss of VSMC betaENaC) will permit those pressure swings to be
      transmitted to the microvasculature in betaENaC m/m mice, thus increasing the
      susceptibility to renal injury and hypertension.

PMID- 22973232
TI  - Effects of second hand smoke on airway secretion and mucociliary clearance.
AB  - The airway acts as the first defense against inhaled pathogens and particulate
      matter from the environment. One major way for the airway to clear inhaled
      foreign objects is through mucociliary clearance (MCC), an important component of
      the respiratory innate immune defense against lung disease. MCC is characterized
      by the upward movement of mucus by ciliary motion that requires a balance between
      the volume and composition of the mucus, adequate periciliary liquid (PCL)
      volume, and normal ciliary beat frequency (CBF). Airway surface fluid (ASL) is a
      thin layer liquid that consists of the highly viscous mucus upper "gel" layer,
      and the watery lubricating lower "sol" layer. Mucus production, secretion and
      clearance are considered to play a critical role in maintenance of airway health
      because it maintains hydration in the airway and traps particulates, bacteria,
      and viruses. Different types of epithelial cells, including secretory cells, and
      ciliated cells, contribute to the MCC function. Cigarette smoke (CS) contains
      chemicals and particulates that significantly affect airway secretion. Active and
      passive CS-induced chronic obstructive pulmonary disease (COPD) is frequently
      associated with hyperplasia of goblet cells and submucosal glands (SMGs), thus
      increasing the secretory capacity of the airways that impairs MCC.

PMID- 22973233
TI  - Airway responsiveness to psychological processes in asthma and health.
AB  - Psychosocial factors have been found to impact airway pathophysiology in
      respiratory disease with considerable consistency. Influences on airway mechanics
      have been studied particularly well. The goal of this article is to review the
      literature on airway responses to psychological stimulation, discuss potential
      pathways of influence, and present a well-established emotion-induction paradigm
      to study airway obstruction elicited by unpleasant stimuli. Observational studies
      have found systematic associations between lung function and daily mood changes.
      The laboratory-based paradigm of bronchoconstrictive suggestion has been used
      successfully to elicit airway obstruction in a substantial proportion of
      asthmatic individuals. Other studies have demonstrated modulation of airway
      responses to standard airway challenges with exercise, allergens, or
      pharmacological agents by psychological factors. Standardized emotion-induction
      techniques have consistently shown airway constriction during unpleasant
      stimulation, with surgery, blood, and injury stimuli being particularly powerful.
      Findings with various forms of stress induction have been more mixed. A number of
      methodological factors may account for variability across studies, such as choice
      of measurement technique, temporal association between stimulation and
      measurement, and the specific quality and intensity of the stimulus material, in
      particular the extent of implied action-orientation. Research has also begun to
      elucidate physiological processes associated with psychologically induced airway
      responses, with vagal excitation and ventilatory influences being the most likely
      candidate pathways, whereas the role of specific central nervous system pathways
      and inflammatory processes has been less studied. The technique of emotion
      induction using films has the potential to become a standardized challenge
      paradigm for the further exploration of airway hyperresponsiveness mediated by
      central nervous system processes.

PMID- 22973234
TI  - Pancreatic stellate cells: a starring role in normal and diseased pancreas.
AB  - While the morphology and function of cells of the exocrine and endocrine pancreas
      have been studied over several centuries, one important cell type in the gland,
      the pancreatic stellate cell (PSC), had remained undiscovered until as recently
      as 20 years ago. Even after its first description in 1982, it was to be another
      16 years before its biology could begin to be studied, because it was only in
      1998 that methods were developed to isolate and culture PSCs from rodent and
      human pancreas. PSCs are now known to play a critical role in pancreatic
      fibrosis, a consistent histological feature of two major diseases of the pancreas
      chronic pancreatitis and pancreatic cancer. In health, PSCs maintain normal
      tissue architecture via regulation of the synthesis and degradation of
      extracellular matrix (ECM) proteins. Recent studies have also implied other
      functions for PSCs as progenitor cells, immune cells or intermediaries in
      exocrine pancreatic secretion in humans. During pancreatic injury, PSCs transform
      from their quiescent phase into an activated, myofibroblast-like phenotype that
      secretes excessive amounts of ECM proteins leading to the fibrosis of chronic
      pancreatitis and pancreatic cancer. An ever increasing number of factors that
      stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are
      being identified and characterized. It is also now established that PSCs interact
      closely with pancreatic cancer cells to facilitate cancer progression. Based on
      these findings, several therapeutic strategies have been examined in experimental
      models of chronic pancreatitis as well as pancreatic cancer, in a bid to
      inhibit/retard PSC activation and thereby alleviate chronic pancreatitis or
      reduce tumor growth in pancreatic cancer. The challenge that remains is to
      translate these pre-clinical developments into clinically applicable treatments
      for patients with chronic pancreatitis and pancreatic cancer.

PMID- 22973236
TI  - Pathogenic mechanism of second hand smoke induced inflammation and COPD.
AB  - Second hand smoke (SHS) introduces thousands of toxic chemicals into the lung,
      including carcinogens and oxidants, which cause direct airway epithelium tissue
      destruction. It can also illicit indirect damage through its effect on signaling
      pathways related to tissue cell repair and by the abnormal induction of
      inflammation into the lung. After repeated exposure to SHS, these symptoms can
      lead to the development of pulmonary inflammatory disorders, including chronic
      obstructive pulmonary disease (COPD). COPD is a severe pulmonary disease
      characterized by chronic inflammation and irreversible tissue destruction. There
      is no causal cure, as the mechanism behind the development and progression of the
      disease is still unknown. Recent discoveries implicate genetic predisposition
      associated with inflammatory response contributed to the development of COPD,
      linked to irregular innate and adaptive immunity, as well as a risk factor for
      cancer. The use of animal models for both cigarette smoke (CS) and SHS associated
      in vivo experiments has been crucial in elucidating the pathogenic mechanisms and
      genetic components involved in inflammation-related development of COPD.

PMID- 22973237
TI  - Alternative methods for characterization of extracellular vesicles.
AB  - Extracellular vesicles (ECVs) are nano-sized vesicles released by all cells in
      vitro as well as in vivo. Their role has been implicated mainly in cell-cell
      communication, but also in disease biomarkers and more recently in gene delivery.
      They represent a snapshot of the cell status at the moment of release and carry
      bioreactive macromolecules such as nucleic acids, proteins, and lipids. A major
      limitation in this emerging new field is the availability/awareness of techniques
      to isolate and properly characterize ECVs. The lack of gold standards makes
      comparing different studies very difficult and may potentially hinder some ECVs
      specific evidence. Characterization of ECVs has also recently seen many advances
      with the use of Nanoparticle Tracking Analysis, flow cytometry, cryo-electron
      microscopy instruments, and proteomic technologies. In this review, we discuss
      the latest developments in translational technologies involving characterization
      methods including the facts in their support and the challenges they face.

PMID- 22973238
TI  - Cardiovascular autonomic nervous system function and aerobic capacity in type 1
      diabetes.
AB  - Impaired cardiovascular autonomic nervous system (ANS) function has been reported
      in type 1 diabetes (T1D) patients. ANS function, evaluated by heart rate
      variability (HRV), systolic blood pressure variability (SBPV), and baroreflex
      sensitivity (BRS), has been linked to aerobic capacity (VO(2peak)) in healthy
      subjects, but this relationship is unknown in T1D. We examined cardiovascular ANS
      function at rest and during function tests, and its relations to VO(2peak) in T1D
      individuals. Ten T1D patients (34 +/- 7 years) and 11 healthy control (CON; 31 +/
      6 years) age and leisure-time physical activity-matched men were studied. ANS
      function was recorded at rest and during active standing and handgrip.
      Determination of VO(2peak) was obtained with a graded cycle ergometer test.
      During ANS recordings SBPV, BRS, and resting HRV did not differ between groups,
      but alpha1 responses to maneuvers in detrended fluctuation analyses were smaller
      in T1D (active standing; 32%, handgrip; 20%, medians) than in CON (active
      standing; 71%, handgrip; 54%, p < 0.05). VO(2peak) was lower in T1D (36 +/- 4 ml
      kg(-1) min(-1)) than in CON (45 +/- 9 ml kg(-1) min(-1), p < 0.05). Resting HRV
      measures, RMSSD, HF, and SD1 correlated with VO(2peak) in CON (p < 0.05) and when
      analyzing groups together. These results suggest that T1D had lower VO(2peak),
      weaker HRV response to maneuvers, but not impaired cardiovascular ANS function at
      rest compared with CON. Resting parasympathetic cardiac activity correlated with
      VO(2peak) in CON but not in T1D. Detrended fluctuation analysis could be a
      sensitive detector of changes in cardiac ANS function in T1D.

PMID- 22973235
TI  - Cardiac electrophysiology in mice: a matter of size.
AB  - Over the last decade, mouse models have become a popular instrument for studying
      cardiac arrhythmias. This review assesses in which respects a mouse heart is a
      miniature human heart, a suitable model for studying mechanisms of cardiac
      arrhythmias in humans and in which respects human and murine hearts differ.
      Section I considers the issue of scaling of mammalian cardiac (electro)
      physiology to body mass. Then, we summarize differences between mice and humans
      in cardiac activation (section II) and the currents underlying the action
      potential in the murine working myocardium (section III). Changes in cardiac
      electrophysiology in mouse models of heart disease are briefly outlined in
      section IV, while section V discusses technical considerations pertaining to
      recording cardiac electrical activity in mice. Finally, section VI offers general
      considerations on the influence of cardiac size on the mechanisms of tachy
      arrhythmias.

PMID- 22973240
TI  - Involvement of atypical protein kinase C in the regulation of cardiac glucose and
      long-chain fatty acid uptake.
AB  - AIM: The signaling pathways involved in the regulation of cardiac GLUT4
      translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake
      are not fully understood. We compared in heart/muscle-specific PKC-lambda
      knockout mice the roles of atypical PKCs (PKC-zeta and PKC-lambda) in regulating
      cardiac glucose and fatty acid uptake. RESULTS: Neither insulin-stimulated nor
      AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC
      lambda ablation in cardiomyocytes. In contrast, myristoylated PKC-zeta
      pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and
      fatty acid uptake by >80% in both wild-type and PKC-lambda-knockout
      cardiomyocytes. In PKC-lambda knockout cardiomyocytes, PKC-zeta is the sole
      remaining atypical PKC isoform, and its expression level is not different from
      wild-type cardiomyocytes, in which it contributes to 29% and 17% of total
      atypical PKC expression and phosphorylation, respectively. CONCLUSION: Taken
      together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated
      glucose uptake into the heart, as well as for insulin-stimulated and AMPK
      mediated fatty acid uptake. However, the residual PKC-zeta activity in PKC-lambda
      knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and
      fatty acid uptake, indicating that atypical PKCs are necessary but not rate
      limiting in the regulation of cardiac substrate uptake and that PKC-lambda and
      PKC-zeta have interchangeable functions in these processes.

PMID- 22973239
TI  - Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem)
      cell-free therapy.
AB  - Mesenchymal stem cells (MSCs) are adult multipotent cells that give rise to
      various cell types of the mesodermal germ layer. MSCs are of great interest in
      the field of regenerative medicine and cancer therapy because of their unique
      ability to home to damaged and cancerous tissue. These cells also regulate the
      immune response and contribute to reparative processes in different pathological
      conditions, including musculoskeletal and cardiovascular diseases. The use of
      MSCs for tissue repair was initially based on the hypothesis that these cells
      home to and differentiate within the injured tissue into specialized cells.
      However, it now appears that only a small proportion of transplanted MSCs
      actually integrate and survive in host tissues. Thus, the predominant mechanism
      by which MSCs participate in tissue repair seems to be related to their paracrine
      activity. Indeed, MSCs provide the microenvironment with a multitude of trophic
      and survival signals including growth factors and cytokines. Recent discoveries
      suggest that lipid microvesicles released by MSCs may also be important in the
      physiological function of these cells. Over the past few years the biological
      relevance of micro- and nano-vesicles released by cells in intercellular
      communication has been established. Alongside the conventional mediators of cell
      secretome, these sophisticated nanovesicles transfer proteins, lipids and, most
      importantly, various forms of RNAs to neighboring cells, thereby mediating a
      variety of biological responses. The physiological role of MSC-derived vesicles
      (MSC-MVs) is currently not well understood. Nevertheless, encouraging results
      indicate that MSC-MVs have similar protective and reparative properties as their
      cellular counterparts in tissue repair and possibly anti-cancer therapy. Thus,
      MSC-MVs represent a promising opportunity to develop novel cell-free therapy
      approaches that might overcome the obstacles and risks associated with the use of
      native or engineered stem cells.

PMID- 22973241
TI  - Parietal contributions to visual working memory depend on task difficulty.
AB  - The nature of parietal contributions to working memory (WM) remain poorly
      understood but of considerable interest. We previously reported that posterior
      parietal damage selectively impaired WM probed by recognition (Berryhill and
      Olson, 2008a). Recent studies provided support using a neuromodulatory technique,
      transcranial direct current stimulation (tDCS) applied to the right parietal
      cortex (P4). These studies confirmed parietal involvement in WM because parietal
      tDCS altered WM performance: anodal current tDCS improved performance in a change
      detection task, and cathodal current tDCS impaired performance on a sequential
      presentation task. Here, we tested whether these complementary results were due
      to different degrees of parietal involvement as a function of WM task demands, WM
      task difficulty, and/or participants' WM capacity. In Experiment 1, we applied
      cathodal and anodal tDCS to the right parietal cortex and tested participants on
      both previously used WM tasks. We observed an interaction between tDCS (anodal,
      cathodal), WM task difficulty, and participants' WM capacity. When the WM task
      was difficult, parietal stimulation (anodal or cathodal) improved WM performance
      selectively in participants with high WM capacity. In the low WM capacity group,
      parietal stimulation (anodal or cathodal) impaired WM performance. These nearly
      equal and opposite effects were only observed when the WM task was challenging,
      as in the change detection task. Experiment 2 probed the interplay of WM task
      difficulty and WM capacity in a parametric manner by varying set size in the WM
      change detection task. Here, the effect of parietal stimulation (anodal or
      cathodal) on the high WM capacity group followed a linear function as WM task
      difficulty increased with set size. The low WM capacity participants were largely
      unaffected by tDCS. These findings provide evidence that parietal involvement in
      WM performance depends on both WM capacity and WM task demands. We discuss these
      findings in terms of alternative WM strategies employed by low and high WM
      capacity individuals. We speculate that low WM capacity individuals do not
      recruit the posterior parietal lobe for WM tasks as efficiently as high WM
      capacity individuals. Consequently, tDCS provides greater benefit to individuals
      with high WM capacity.

PMID- 22973242
TI  - Motor Consciousness during Intention-Based and Stimulus-Based Actions: Modulating
      Attention Resources through Mindfulness Meditation.
AB  - Mindfulness-Based Stress Reduction meditation (MBSR) may offer optimal
      performance through heightened attention for increased body consciousness. To
      test this hypothesis, MBSR effects were assessed on the simple task of lifting an
      object. A dual task paradigm was included to assess the opposite effect of a
      limited amount of attention on motor consciousness. In a stimulus-based
      condition, the subjects' task was to lift an object that was hefted with weights.
      In an intentional-based condition, subjects were required to lift a light object
      while imagining that the object was virtually heavier and thus, adjust their grip
      voluntarily. The degree of motor consciousness was evaluated by calculating
      correlation factors for each participant between the grip force level used during
      the lift trial ("lift the object") and that used during its associated reproduce
      trial ("without lifting, indicate the force you think you used in the previous
      trial"). Under dual task condition, motor consciousness decreased for intention-
      and stimulus-based actions, revealing the importance of top-down attention for
      building the motor representation that guides action planning. For MBSR-experts,
      heightened attention provided stronger levels of motor consciousness; this was
      true for both intention and stimulus-based actions. For controls, heightened
      attention decreased the capacity to reproduce force levels, suggesting that
      voluntary top-down attention interfered with the automatic bottom-up emergence of
      body sensations. Our results provide strong arguments for involvement of two
      types of attention for the emergence of motor consciousness. Bottom-up attention
      would serve as an amplifier of motor-sensory afferences; top-down attention would
      help transfer the motor-sensory content from a preconscious to a conscious state
      of processing. MBSR would be a specific state for which both types of attention
      are optimally combined to provide experts with total experiences of their body in
      movement.

PMID- 22973243
TI  - The Thaayorre think of Time Like They Talk of Space.
AB  - Around the world, it is common to both talk and think about time in terms of
      space. But does our conceptualization of time simply reflect the space/time
      metaphors of the language we speak? Evidence from the Australian language Kuuk
      Thaayorre suggests not. Kuuk Thaayorre speakers do not employ active spatial
      metaphors in describing time. But this is not to say that spatial language is
      irrelevant to temporal construals: non-linguistic representations of time are
      shown here to covary with the linguistic system of describing space. This article
      contrasts two populations of ethnic Thaayorre from Pormpuraaw - one comprising
      Kuuk Thaayorre/English bilinguals and the other English-monolinguals - in order
      to distinguish the effects of language from environmental and other factors.
      Despite their common physical, social, and cultural context, the two groups
      differ in their representations of time in ways that are congruent with the
      language of space in Kuuk Thaayorre and English, respectively. Kuuk
      Thaayorre/English bilinguals represent time along an absolute east-to-west axis,
      in alignment with the high frequency of absolute frame of reference terms in Kuuk
      Thaayorre spatial description. The English-monolinguals, in contrast, represent
      time from left-to-right, aligning with the dominant relative frame of reference
      in English spatial description. This occurs in the absence of any east-to-west
      metaphors in Kuuk Thaayorre, or left-to-right metaphors in English. Thus the way
      these two groups think about time appears to reflect the language of space and
      not the language of time.

PMID- 22973244
TI  - Nepotistic patterns of violent psychopathy: evidence for adaptation?
AB  - Psychopaths routinely disregard social norms by engaging in selfish, antisocial,
      often violent behavior. Commonly characterized as mentally disordered, recent
      evidence suggests that psychopaths are executing a well-functioning, if
      unscrupulous strategy that historically increased reproductive success at the
      expense of others. Natural selection ought to have favored strategies that spared
      close kin from harm, however, because actions affecting the fitness of genetic
      relatives contribute to an individual's inclusive fitness. Conversely, there is
      evidence that mental disorders can disrupt psychological mechanisms designed to
      protect relatives. Thus, mental disorder and adaptation accounts of psychopathy
      generate opposing hypotheses: psychopathy should be associated with an increase
      in the victimization of kin in the former account but not in the latter. Contrary
      to the mental disorder hypothesis, we show here in a sample of 289 violent
      offenders that variation in psychopathy predicts a decrease in the genetic
      relatedness of victims to offenders; that is, psychopathy predicts an increased
      likelihood of harming non-relatives. Because nepotistic inhibition in violence
      may be caused by dispersal or kin discrimination, we examined the effects of
      psychopathy on (1) the dispersal of offenders and their kin and (2) sexual
      assault frequency (as a window on kin discrimination). Although psychopathy was
      negatively associated with coresidence with kin and positively associated with
      the commission of sexual assault, it remained negatively associated with the
      genetic relatedness of victims to offenders after removing cases of offenders who
      had coresided with kin and cases of sexual assault from the analyses. These
      results stand in contrast to models positing psychopathy as a pathology, and
      provide support for the hypothesis that psychopathy reflects an evolutionary
      strategy largely favoring the exploitation of non-relatives.

PMID- 22973245
TI  - Temporal Preparation Driven by Rhythms is Resistant to Working Memory
      Interference.
AB  - It has been recently shown that temporal orienting demands controlled attention
      (Capizzi et al., 2012). However, there is current debate on whether temporal
      preparation guided by regular rhythms also requires the generation of endogenous
      temporal expectancies or rather involves a mechanism independent of executive
      control processes. We investigated this issue by using a dual-task paradigm in
      two different experiments. In Experiment 1, the single-task condition measured
      reaction time to respond to the onset of an auditory stimulus preceded by either
      a regular or an irregular auditory rhythm. The dual-task condition additionally
      included a working memory task, which demanded mental counting and updating. In
      Experiment 2, the simultaneously WM task was a variant of the Sternberg Task. We
      hypothesized that, if temporal preparation induced by rhythms did not involve
      executive processing, it would not be interfered by the simultaneous working
      memory task. The results showed that participants could anticipate the moment of
      target onset on the basis of the regular rhythm and, more important, this ability
      resisted the interference from the double task condition in both experiments.
      This finding supports that temporal preparation induced by rhythms, in contrast
      to temporal orienting, does not require resources of executive control.

PMID- 22973246
TI  - Goal-side selection in soccer penalty kicking when viewing natural scenes.
AB  - The present study investigates the influence of goalkeeper displacement on goal
      side selection in soccer penalty kicking. Facing a penalty situation,
      participants viewed photo-realistic images of a goalkeeper and a soccer goal. In
      the action selection task, they were asked to kick to the greater goal-side, and
      in the perception task, they indicated the position of the goalkeeper on the goal
      line. To this end, the goalkeeper was depicted in a regular goalkeeping posture,
      standing either in the exact middle of the goal or being displaced at different
      distances to the left or right of the goal's center. Results showed that the
      goalkeeper's position on the goal line systematically affected goal-side
      selection, even when participants were not aware of the displacement. These
      findings provide further support for the notion that the implicit processing of
      the stimulus layout in natural scenes can effect action selection in complex
      environments, such in soccer penalty shooting.

PMID- 22973247
TI  - From risk-seeking to risk-averse: the development of economic risk preference
      from childhood to adulthood.
AB  - Adolescence is often described as a period of heightened risk-taking. Adolescents
      are notorious for impulsivity, emotional volatility, and risky behaviors such as
      drinking and driving under the influence of alcohol. By contrast, we found that
      risk-taking declines linearly from childhood to adulthood when individuals make
      choices over monetary gambles. Further, with age we found increases in the
      sensitivity to economic risk, defined as the degree to which a preference for
      assured monetary gains over a risky payoff depends upon the variability in the
      risky payoff. These findings indicate that decisions about economic risk may
      follow a different developmental trajectory than other kinds of risk-taking, and
      that changes in sensitivity to risk may be a major factor in the development of
      mature risk aversion.

PMID- 22973248
TI  - Pupil dilation: a fingerprint of temporal selection during the "attentional
      blink".
AB  - Pupil dilation indexes cognitive events of behavioral relevance, like the storage
      of information to memory and the deployment of attention. Yet, given the slow
      temporal response of the pupil dilation, it is not known from previous studies
      whether the pupil can index cognitive events in the short time scale of ~100 ms.
      Here we measured the size of the pupil in the Attentional Blink (AB) experiment,
      a classic demonstration of attentional limitations in processing rapidly
      presented stimuli. In the AB, two targets embedded in a sequence have to be
      reported and the second stimulus is often missed if presented between 200 and 500
      ms after the first. We show that pupil dilation can be used as a marker of
      cognitive processing in AB, revealing both the timing and amount of cognitive
      processing. Specifically, we found that in the time range where the AB is known
      to occur: (i) the pupil dilation was delayed, mimicking the pattern of response
      times in the Psychological Refractory Period (PRP) paradigm, (ii) the amplitude
      of the pupil was reduced relative to that of larger lags, even for correctly
      identified targets, and (iii) the amplitude of the pupil was smaller for missed
      than for correctly reported targets. These results support two-stage theories of
      the Attentional Blink where a second processing stage is delayed inside the
      interference regime, and indicate that the pupil dilation can be used as a marker
      of cognitive processing in the time scale of ~100 ms. Furthermore, given the
      known relation between the pupil dilation and the activity of the locus
      coeruleus, our results also support theories that link the serial stage to the
      action of a specific neuromodulator, norepinephrine.

PMID- 22973249
TI  - Individual variation in the late positive complex to semantic anomalies.
AB  - It is well-known that, within ERP paradigms of sentence processing, semantically
      anomalous words elicit N400 effects. Less clear, however, is what happens after
      the N400. In some cases N400 effects are followed by Late Positive Complexes
      (LPC), whereas in other cases such effects are lacking. We investigated several
      factors which could affect the LPC, such as contextual constraint, inter
      individual variation, and working memory. Seventy-two participants read sentences
      containing a semantic manipulation (Whipped cream tastes sweet/anxious and
      creamy). Neither contextual constraint nor working memory correlated with the
      LPC. Inter-individual variation played a substantial role in the elicitation of
      the LPC with about half of the participants showing a negative response and the
      other half showing an LPC. This individual variation correlated with a syntactic
      ERP as well as an alternative semantic manipulation. In conclusion, our results
      show that inter-individual variation plays a large role in the elicitation of the
      LPC and this may account for the diversity in LPC findings in language research.

PMID- 22973250
TI  - Structural Variation within the Amygdala and Ventromedial Prefrontal Cortex
      Predicts Memory for Impressions in Older Adults.
AB  - Research has shown that lesions to regions involved in social and emotional
      cognition disrupt socioemotional processing and memory. We investigated how
      structural variation of regions involved in socioemotional memory [ventromedial
      prefrontal cortex (vmPFC), amygdala], as opposed to a region implicated in
      explicit memory (hippocampus), affected memory for impressions in young and older
      adults. Anatomical MRI scans for 15 young and 15 older adults were obtained and
      reconstructed to gather information about cortical thickness and subcortical
      volume. Young adults had greater amygdala and hippocampus volumes than old, and
      thicker left vmPFC than old, although right vmPFC thickness did not differ across
      the age groups. Participants formed behavior-based impressions and responded to
      interpersonally meaningful, social but interpersonally irrelevant, or non-social
      prompts, and completed a memory test. Results showed that greater left amygdala
      volume predicted enhanced overall memory for impressions in older but not younger
      adults. Increased right vmPFC thickness in older, but not younger, adults
      correlated with enhanced memory for impressions formed in the interpersonally
      meaningful context. Hippocampal volume was not predictive of social memory in
      young or older adults. These findings demonstrate the importance of structural
      variation in regions linked to socioemotional processing in the retention of
      impressions with age, and suggest that the amygdala and vmPFC play integral roles
      when encoding and retrieving social information.

PMID- 22973252
TI  - Default Positions: How Neuroscience's Historical Legacy has Hampered
      Investigation of the Resting Mind.
AB  - The puzzle of the brain and mind at rest - their so-called default state - is
      strongly influenced by the historical precedents that led to its emergence as a
      scientific question. What eventually became the default-mode network (DMN) was
      inaugurated via meta-analysis to explain the observation that the baseline "at
      rest" condition was concealing a pattern of neural activations in anterior and
      posterior midline brain regions that were not commonly seen in external-task
      driven experiments. One reason why these activations have puzzled scientists is
      because psychology and cognitive neuroscience have historically been focused on
      paradigms built around external tasks, and so lacked the scientific and
      theoretical tools to interpret the cognitive functions of the DMN. This
      externally-focused bias led to the erroneous assumption that the DMN is the
      primary neural system active at rest, as well as the assumption that this network
      serves non-goal-directed functions. Although cognitive neuroscience now embraces
      the need to decode the meaning of self-generated neural activity, a more
      deliberate and comprehensive framework will be needed before the puzzle of the
      wandering mind can be laid to rest.

PMID- 22973251
TI  - Neural Oscillations Carry Speech Rhythm through to Comprehension.
AB  - A key feature of speech is the quasi-regular rhythmic information contained in
      its slow amplitude modulations. In this article we review the information
      conveyed by speech rhythm, and the role of ongoing brain oscillations in
      listeners' processing of this content. Our starting point is the fact that speech
      is inherently temporal, and that rhythmic information conveyed by the amplitude
      envelope contains important markers for place and manner of articulation,
      segmental information, and speech rate. Behavioral studies demonstrate that
      amplitude envelope information is relied upon by listeners and plays a key role
      in speech intelligibility. Extending behavioral findings, data from neuroimaging 
      particularly electroencephalography (EEG) and magnetoencephalography (MEG) -
      point to phase locking by ongoing cortical oscillations to low-frequency
      information (~4-8 Hz) in the speech envelope. This phase modulation effectively
      encodes a prediction of when important events (such as stressed syllables) are
      likely to occur, and acts to increase sensitivity to these relevant acoustic
      cues. We suggest a framework through which such neural entrainment to speech
      rhythm can explain effects of speech rate on word and segment perception (i.e.,
      that the perception of phonemes and words in connected speech is influenced by
      preceding speech rate). Neuroanatomically, acoustic amplitude modulations are
      processed largely bilaterally in auditory cortex, with intelligible speech
      resulting in differential recruitment of left-hemisphere regions. Notable among
      these is lateral anterior temporal cortex, which we propose functions in a domain
      general fashion to support ongoing memory and integration of meaningful input.
      Together, the reviewed evidence suggests that low-frequency oscillations in the
      acoustic speech signal form the foundation of a rhythmic hierarchy supporting
      spoken language, mirrored by phase-locked oscillations in the human brain.

PMID- 22973253
TI  - Statistical assumptions of substantive analyses across the general linear model:
      a mini-review.
AB  - The validity of inferences drawn from statistical test results depends on how
      well data meet associated assumptions. Yet, research (e.g., Hoekstra et al.,
      2012) indicates that such assumptions are rarely reported in literature and that
      some researchers might be unfamiliar with the techniques and remedies that are
      pertinent to the statistical tests they conduct. This article seeks to support
      researchers by concisely reviewing key statistical assumptions associated with
      substantive statistical tests across the general linear model. Additionally, the
      article reviews techniques to check for statistical assumptions and identifies
      remedies and problems if data do not meet the necessary assumptions.

PMID- 22973255
TI  - Emotion and deliberative reasoning in moral judgment.
AB  - According to an influential dual-process model, a moral judgment is the outcome
      of a rapid, affect-laden process and a slower, deliberative process. If these
      outputs conflict, decision time is increased in order to resolve the conflict.
      Violations of deontological principles proscribing the use of personal force to
      inflict intentional harm are presumed to elicit negative affect which biases
      judgments early in the decision-making process. This model was tested in three
      experiments. Moral dilemmas were classified using (a) decision time and consensus
      as measures of system conflict and (b) the aforementioned deontological criteria.
      In Experiment 1, decision time was either unlimited or reduced. The dilemmas
      asked whether it was appropriate to take a morally questionable action to produce
      a "greater good" outcome. Limiting decision time reduced the proportion of
      utilitarian ("yes") decisions, but contrary to the model's predictions, (a)
      vignettes that involved more deontological violations logged faster decision
      times, and (b) violation of deontological principles was not predictive of
      decisional conflict profiles. Experiment 2 ruled out the possibility that time
      pressure simply makes people more like to say "no." Participants made a first
      decision under time constraints and a second decision under no time constraints.
      One group was asked whether it was appropriate to take the morally questionable
      action while a second group was asked whether it was appropriate to refuse to
      take the action. The results replicated that of Experiment 1 regardless of
      whether "yes" or "no" constituted a utilitarian decision. In Experiment 3,
      participants rated the pleasantness of positive visual stimuli prior to making a
      decision. Contrary to the model's predictions, the number of deontological
      decisions increased in the positive affect rating group compared to a group that
      engaged in a cognitive task or a control group that engaged in neither task.
      These results are consistent with the view that early moral judgments are
      influenced by affect. But they are inconsistent with the view that (a) violation
      of deontological principles are predictive of differences in early, affect-based
      judgment or that (b) engaging in tasks that are inconsistent with the negative
      emotional responses elicited by such violations diminishes their impact.

PMID- 22973256
TI  - Does primary narcissism exist in newborn babies? Evidence from sleep science.

PMID- 22973254
TI  - Music and early language acquisition.
AB  - Language is typically viewed as fundamental to human intelligence. Music, while
      recognized as a human universal, is often treated as an ancillary ability - one
      dependent on or derivative of language. In contrast, we argue that it is more
      productive from a developmental perspective to describe spoken language as a
      special type of music. A review of existing studies presents a compelling case
      that musical hearing and ability is essential to language acquisition. In
      addition, we challenge the prevailing view that music cognition matures more
      slowly than language and is more difficult; instead, we argue that music learning
      matches the speed and effort of language acquisition. We conclude that music
      merits a central place in our understanding of human development.

PMID- 22973257
TI  - The effects of self-controlled video feedback on the learning of the basketball
      set shot.
AB  - Allowing learners to control some aspect of instructional support (e.g.,
      augmented feedback) appears to facilitate motor skill acquisition. No studies,
      however, have examined self-controlled (SC) video feedback without the provision
      of additional attentional cueing. The purpose of this study was to extend
      previous SC research using video feedback about movement form for the basketball
      set shot without explicitly directing attention to specific aspects of the
      movement. The SC group requested video feedback of their performance following
      any trial during the acquisition phase. The yoked group received feedback
      according to a schedule created by a SC counterpart. During acquisition
      participants were also allowed to view written instructional cues at any time.
      Results revealed that the SC group had significantly higher form scores during
      the transfer phase and utilized the instructional cues more frequently during
      acquisition. Post-training questionnaire responses indicated no preference for
      requesting or receiving feedback following good trials as reported by
      Chiviacowsky and Wulf (2002, 2005). The nature of the task was such that
      participants could have assigned both positive and negative evaluations to
      different aspects of the movement during the same trial. Thus, the lack of
      preferences along with the similarity in scores for feedback and no-feedback
      trials may simply have reflected this complexity. Importantly, however, the
      results indicated that SC video feedback conferred a learning benefit without the
      provision of explicit additional attentional cueing.

PMID- 22973258
TI  - Setting Up a Bioluminescence Resonance Energy Transfer High throughput Screening
      Assay to Search for Protein/Protein Interaction Inhibitors in Mammalian Cells.
AB  - Each step of the cell life and its response or adaptation to its environment are
      mediated by a network of protein/protein interactions termed "interactome." Our
      knowledge of this network keeps growing due to the development of sensitive
      techniques devoted to study these interactions. The bioluminescence resonance
      energy transfer (BRET) technique was primarily developed to allow the dynamic
      monitoring of protein/protein interactions (PPI) in living cells, and has widely
      been used to study receptor activation by intra- or extra-molecular
      conformational changes within receptors and activated complexes in mammal cells.
      Some interactions are described as crucial in human pathological processes, and a
      new class of drugs targeting them has recently emerged. The BRET method is well
      suited to identify inhibitors of PPI and here is described why and how to set up
      and optimize a high throughput screening assay based on BRET to search for such
      inhibitory compounds. The different parameters to take into account when
      developing such BRET assays in mammal cells are reviewed to give general
      guidelines: considerations on the targeted interaction, choice of BRET version,
      inducibility of the interaction, kinetic of the monitored interaction, and of the
      BRET reading, influence of substrate concentration, number of cells and medium
      composition used on the Z' factor, and expected interferences from colored or
      fluorescent compounds.

PMID- 22973259
TI  - Mathematical models for quantitative assessment of bioluminescence resonance
      energy transfer: application to seven transmembrane receptors oligomerization.
AB  - The idea that seven transmembrane receptors (7TMRs; also designated G-protein
      coupled receptors, GPCRs) might form dimers or higher order oligomeric complexes
      was formulated more than 20 years ago and has been intensively studied since
      then. In the last decade, bioluminescence resonance energy transfer (BRET) has
      been one of the most frequently used biophysical methods for studying 7TMRs
      oligomerization. This technique enables monitoring physical interactions between
      protein partners in living cells fused to donor and acceptor moieties. It relies
      on non-radiative transfer of energy between donor and acceptor, depending on
      their intermolecular distance (1-10 nm) and relative orientation. Results derived
      from BRET-based techniques are very persuasive; however, they need appropriate
      controls and critical interpretation. To overcome concerns about the specificity
      of BRET-derived results, a set of experiments has been proposed, including
      negative control with a non-interacting receptor or protein, BRET dilution,
      saturation, and competition assays. This article presents the theoretical
      background behind BRET assays, then outlines mathematical models for quantitative
      interpretation of BRET saturation and competition assay results, gives examples
      of their utilization and discusses the possibilities of quantitative analysis of
      data generated with other RET-based techniques.

PMID- 22973260
TI  - Incretin hormones as immunomodulators of atherosclerosis.
AB  - Atherosclerosis results from endothelial cell dysfunction and inflammatory
      processes affecting both macro- and microvasculature which are involved in
      vascular diabetic complications. Glucagon-like peptide-1 (GLP-1) is an incretin
      hormone responsible for amplification of insulin secretion when nutrients are
      given orally as opposed to intravenously and it retains its insulinotropic
      activity in patients with type 2 diabetes mellitus (T2D). GLP-1 based therapies,
      such as GLP-1 receptor (GLP-1R) agonists and inhibitors of dipeptidyl peptidase
      4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients
      with T2D. Recent experimental model studies have established that GLP-1R mRNA is
      widely expressed in several immune cells. Moreover, its activation contributes to
      the regulation of both thymocyte and peripheral T cells proliferation and is
      involved in the maintenance of peripheral regulatory T cells. GLP-1R is also
      expressed in endothelial and smooth muscle cells. The effect of incretin hormones
      on atherosclerogenesis have recently been studied in animal models of
      apolipoprotein E-deficient mice (apoE(-/-)). These studies have demonstrated that
      treatment with incretin hormones or related compounds suppresses the progression
      of atherosclerosis and macrophage infiltration in the arterial wall as well as a
      marked anti-oxidative and anti-inflammatory effect on endothelial cells. This
      effect may have a major impact on the attenuation of atherosclerosis and may help
      in the design of new therapies for cardiovascular disease in patients with type 2
      diabetes.

PMID- 22973261
TI  - Comparison of water availability effect on ammonia-oxidizing bacteria and archaea
      in microcosms of a Chilean semiarid soil.
AB  - Water availability is the main limiting factor in arid soils; however, few
      studies have examined the effects of drying and rewetting on nitrifiers from
      these environments. The effect of water availability on the diversity of ammonia
      oxidizing bacteria (AOB) and archaea (AOA) from a semiarid soil of the Chilean
      sclerophyllous matorral was determined by microcosm assays. The addition of water
      every 14 days to reach 60% of the WHC significantly increased nitrate content in
      rewetted soil microcosms (p < 0.001). This stimulation of net nitrification by
      water addition was inhibited by acetylene addition at 100 Pa. The composition of
      AOA and AOB assemblages from the soils microcosms was determined by clone
      sequencing of amoA genes (A-amoA and B-amoA, respectively), and the 16S rRNA
      genes specific for beta-proteobacteria (beta-amo). Sequencing of beta-amo genes
      has revealed representatives of Nitrosomonas and Nitrosospira while B-amoA clones
      consisted only of Nitrosospira sequences. Furthermore, all clones from the
      archaeal amoA gene library (A-amoA) were related to "mesophilic Crenarchaeota"
      sequences (actually, reclassified as the phylum Thaumarchaeota). The effect of
      water availability on both microbial assemblages structure was determined by T
      RFLP profiles using the genetic markers amoA for archaea, and beta-amo for
      bacteria. While AOA showed fluctuations in some T-RFs, AOB structure remained
      unchanged by water pulses. The relative abundance of AOA and AOB was estimated by
      the Most Probable Number coupled to Polymerase Chain Reaction (MPN-PCR) assay.
      AOB was the predominant guild in this soil and higher soil water content did not
      affect their abundance, in contrast to AOA, which slightly increased under these
      conditions. Therefore, these results suggest that water addition to these
      semiarid soil microcosms could favor archaeal contribution to ammonium oxidation.

PMID- 22973263
TI  - The Parasitic Dinoflagellates Blastodinium spp. Inhabiting the Gut of Marine,
      Planktonic Copepods: Morphology, Ecology, and Unrecognized Species Diversity.
AB  - Blastodinium is a genus of dinoflagellates that live as parasites in the gut of
      marine, planktonic copepods in the World's oceans and coastal waters. The
      taxonomy, phylogeny, and physiology of the genus have only been explored to a
      limited degree and, based on recent investigations, we hypothesize that the
      morphological and genetic diversity within this genus may be considerably larger
      than presently recognized. To address these issues, we obtained 18S rDNA and ITS
      gene sequences for Blastodinium specimens of different geographical origins,
      including representatives of the type species. This genetic information was in
      some cases complemented with new morphological, ultrastructural, physiological,
      and ecological data. Because most current knowledge about Blastodinium and its
      effects on copepod hosts stem from publications more than half a century old, we
      here summarize and discuss the existing knowledge in relation to the new data
      generated. Most Blastodinium species possess functional chloroplasts, but the
      parasitic stage, the trophocyte, has etioplasts and probably a limited
      photosynthetic activity. Sporocytes and swarmer cells have well-developed
      plastids and plausibly acquire part of their organic carbon needs through
      photosynthesis. A few species are nearly colorless with no functional
      chloroplasts. The photosynthetic species are almost exclusively found in warm,
      oligotrophic waters, indicating a life strategy that may benefit from copepods as
      microhabitats for acquiring nutrients in a nutrient-limited environment. As
      reported in the literature, monophyly of the genus is moderately supported, but
      the three main groups proposed by Chatton in 1920 are consistent with molecular
      data. However, we demonstrate an important genetic diversity within the genus and
      provide evidences for new groups and the presence of cryptic species. Finally, we
      discuss the current knowledge on the occurrence of Blastodinium spp. and their
      potential impact on natural copepod populations.

PMID- 22973262
TI  - Vaccine and immunotherapeutic approaches for the prevention of cryptococcosis:
      lessons learned from animal models.
AB  - Cryptococcus neoformans and C. gattii, the predominant etiological agents of
      cryptococcosis, can cause life-threatening infections of the central nervous
      system in immunocompromised and immunocompetent individuals. Cryptococcal
      meningoencephalitis is the most common disseminated fungal infection in AIDS
      patients, and C. neoformans remains the third most common invasive fungal
      infection among organ transplant recipients. Current anti-fungal drug therapies
      are oftentimes rendered ineffective due to drug toxicity, the emergence of drug
      resistant organisms, and/or the inability of the host's immune defenses to assist
      in eradication of the yeast. Therefore, there remains an urgent need for the
      development of immune-based therapies and/or vaccines to combat cryptococcosis.
      Studies in animal models have demonstrated the efficacy of various vaccination
      strategies and immune therapies to induce protection against cryptococcosis. This
      review will summarize the lessons learned from animal models supporting the
      feasibility of developing immunotherapeutics and vaccines to prevent
      cryptococcosis.

PMID- 22973264
TI  - Structural basis for specific recognition of substrates by sapovirus protease.
AB  - Sapovirus (SaV) protease catalyzes cleavage of the peptide bonds at six sites of
      a viral polyprotein for the viral replication and maturation. However, the
      mechanisms by which the protease recognizes the distinct sequences of the six
      cleavage sites remain poorly understood. Here we examined this issue by
      computational and experimental approaches. A structural modeling and docking
      study disclosed two small clefts on the SaV protease cavity that allow the stable
      and functional binding of substrates to the catalytic cavity via aromatic
      stacking and electrostatic interactions. An information entropy study and a site
      directed mutagenesis study consistently suggested variability of the two clefts
      under functional constraints. Using this information, we identified three
      chemical compounds that had structural and spatial features resembling those of
      the substrate amino acid residues bound to the two clefts and that exhibited an
      inhibitory effect on SaV protease in vitro. These results suggest that the two
      clefts provide structural base points to realize the functional binding of
      various substrates.

PMID- 22973266
TI  - Juruin: an antifungal peptide from the venom of the Amazonian Pink Toe spider,
      Avicularia juruensis, which contains the inhibitory cystine knot motif.
AB  - The aim of this study was to screen the venom of the theraposid spider Avicularia
      juruensis for the identification of antimicrobial peptides (AMPs) which could be
      further used as prototypes for drug development. Eleven AMPs, named juruentoxins,
      with molecular weight ranging from 3.5 to 4.5 kDa, were identified by mass
      spectrometry after the soluble venom was separated by high performance liquid
      chromatography. Juruentoxins have a putative inhibitory cystine knot (ICK) motif,
      generally found in neurotoxins, which are also resistant to proteolysis. One
      juruentoxin that has 38 amino acid residues and three disulfide bonds were
      characterized, to which we proposed the name Juruin. Based on liquid growth
      inhibition assays, it has potent antifungal activity in the micromolar range.
      Importantly, Juruin lacks haemolytic activity on human erythrocytes at the
      antimicrobial concentrations. Based on the amino acid sequence, it is highly
      identical to the insecticidal peptides from the theraposid spiders Selenocosmia
      huwena, Chilobrachys jingzhao, and Haplopelma schmidti from China, indicating
      they belong to a group of conserved toxins which are likely to inhibit voltage
      gated ion channels. Juruin is a cationic AMP, and Lys22 and Lys23 show maximum
      positive charge localization that might be important for receptor recognition.
      Although it shows marked sequence similarity to neurotoxic peptides, Juruin is a
      novel exciting molecule with potent antifungal activity, which could be used as a
      novel template for development of drugs against clinical resistant fungi strains.

PMID- 22973265
TI  - Adult T-cell leukemia: a review of epidemiological evidence.
AB  - Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T
      cell leukemia virus type I (HTLV-1) infection and often occurs in HTLV-1-endemic
      areas, such as southwestern Japan, the Caribbean islands, Central and South
      America, Intertropical Africa, and Middle East. To date, many epidemiological
      studies have been conducted to investigate the incidence of ATL among general
      population or HTLV-1 carriers and to identify a variety of laboratory, molecular,
      and host-specific markers to be possible predictive factors for developing ATL
      because HTLV-1 infection alone is not sufficient to develop ATL. This literature
      review focuses on the epidemiology of ATL and the risk factors for the
      development of ATL from HTLV-1 carriers, while keeping information on the
      epidemiology of HTLV-1 to a minimum. The main lines of epidemiological evidence
      are: (1) ATL occurs mostly in adults, at least 20-30 years after the HTLV-1
      infection, (2) age at onset differs across geographic areas: the average age in
      the Central and South America (around 40 years old) is younger than that in Japan
      (around 60 years old), (3) ATL occurs in those infected in childhood, but seldom
      occurs in those infected in adulthood, (4) male carriers have about a three- to
      fivefold higher risk of developing ATL than female, (5) the estimated lifetime
      risk of developing ATL in HTLV-1 carriers is 6-7% for men and 2-3% for women in
      Japan, (6) a low anti-Tax reactivity, a high soluble interleukin-2 receptor
      level, a high anti-HTLV-1 titer, and high levels of circulating abnormal
      lymphocytes and white blood cell count are accepted risk factors for the
      development of ATL, and (7) a higher proviral load (more than 4 copies/100
      peripheral blood mononuclear cells) is an independent risk factor for progression
      of ATL. Nevertheless, the current epidemiological evidence is insufficient to
      fully understand the oncogenesis of ATL. Further well-designed epidemiological
      studies are needed.

PMID- 22973267
TI  - Acidophilic algae isolated from mine-impacted environments and their roles in
      sustaining heterotrophic acidophiles.
AB  - Two acidophilic algae, identified as strains of Chlorella protothecoides var.
      acidicola and Euglena mutabilis, were isolated in pure culture from abandoned
      copper mines in Spain and Wales and grown in pH- and temperature-controlled
      bioreactors. The Chlorella isolate grew optimally at pH 2.5 and 30 degrees C,
      with a corresponding culture doubling time of 9 h. The isolates displayed similar
      tolerance (10-50 mM) to four transition metals tested. Growth of the algae in
      liquid media was paralleled with increasing concentrations of dissolved organic
      carbon (DOC). Glycolic acid was identified as a significant component (12-14%) of
      total DOC. Protracted incubation resulted in concentrations of glycolic acid
      declining in both cases, and glycolic acid added to a culture of Chlorella
      incubated in the dark was taken up by the alga (~100% within 3 days). Two
      monosaccharides were identified in cell-free liquors of each algal isolate:
      fructose and glucose (Chlorella), and mannitol and glucose (Euglena). These were
      rapidly metabolized by acidophilic heterotrophic bacteria (Acidiphilium and
      Acidobacterium spp.) though only fructose was utilized by the more fastidious
      heterotroph "Acidocella aromatica." The significance of algae in promoting the
      growth of iron- (and sulfate-) reducing heterotrophic acidophiles that are
      important in remediating mine-impacted waters (MIWs) is discussed.

PMID- 22973268
TI  - Challenges and opportunities in estimating viral genetic diversity from next
      generation sequencing data.
AB  - Many viruses, including the clinically relevant RNA viruses HIV (human
      immunodeficiency virus) and HCV (hepatitis C virus), exist in large populations
      and display high genetic heterogeneity within and between infected hosts.
      Assessing intra-patient viral genetic diversity is essential for understanding
      the evolutionary dynamics of viruses, for designing effective vaccines, and for
      the success of antiviral therapy. Next-generation sequencing (NGS) technologies
      allow the rapid and cost-effective acquisition of thousands to millions of short
      DNA sequences from a single sample. However, this approach entails several
      challenges in experimental design and computational data analysis. Here, we
      review the entire process of inferring viral diversity from sample collection to
      computing measures of genetic diversity. We discuss sample preparation, including
      reverse transcription and amplification, and the effect of experimental
      conditions on diversity estimates due to in vitro base substitutions, insertions,
      deletions, and recombination. The use of different NGS platforms and their
      sequencing error profiles are compared in the context of various applications of
      diversity estimation, ranging from the detection of single nucleotide variants
      (SNVs) to the reconstruction of whole-genome haplotypes. We describe the
      statistical and computational challenges arising from these technical artifacts,
      and we review existing approaches, including available software, for their
      solution. Finally, we discuss open problems, and highlight successful biomedical
      applications and potential future clinical use of NGS to estimate viral
      diversity.

PMID- 22973270
TI  - Competition for IL-2 between Regulatory and Effector T Cells to Chisel Immune
      Responses.
AB  - In this review we discuss how the competition for cytokines between different
      cells of the immune system can shape the system wide immune response. We focus on
      interleukin-2 (IL-2) secretion by activated effector T cells (T(eff)) and on the
      competition for IL-2 consumption between T(eff) and regulatory T cells (T(reg)).
      We discuss the evidence for the mechanism in which the depletion of IL-2 by
      T(reg) cells would be sufficient to suppress an autoimmune response, yet not
      strong enough to prevent an immune response. We present quantitative estimations
      and summarize our modeling effort to show that the tug-of-war between T(reg) and
      T(eff) cells for IL-2 molecules can be won by T(reg) cells in the case of weak
      activation of T(eff) leading to the suppression of the immune response. Or, for
      strongly activated T(eff) cells, it can be won by T(eff) cells bringing about the
      activation of the whole adaptive immune system. Finally, we discuss some recent
      applications attempting to achieve clinical effects through the modulation of IL
      2 consumption by T(reg) compartment.

PMID- 22973269
TI  - HTLV-1 Rex: the courier of viral messages making use of the host vehicle.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus causing an
      aggressive T-cell malignancy, adult T-cell leukemia (ATL). Although HTLV-1 has a
      compact RNA genome, it has evolved elaborate mechanisms to maximize its coding
      potential. The structural proteins Gag, Pro, and Pol are encoded in the unspliced
      form of viral mRNA, whereas the Env protein is encoded in singly spliced viral
      mRNA. Regulatory and accessory proteins, such as Tax, Rex, p30II, p12, and p13,
      are translated only from fully spliced mRNA. For effective viral replication,
      translation from all forms of HTLV-1 transcripts has to be achieved in concert,
      although unspliced mRNA are extremely unstable in mammalian cells. It has been
      well recognized that HTLV-1 Rex enhances the stability of unspliced and singly
      spliced HTLV-1 mRNA by promoting nuclear export and thereby removing them from
      the splicing site. Rex specifically binds to the highly structured Rex responsive
      element (RxRE) located at the 3' end of all HTLV-1 mRNA. Rex then binds to the
      cellular nuclear exporter, CRM1, via its nuclear export signal domain and the Rex
      viral transcript complex is selectively exported from the nucleus to the
      cytoplasm for effective translation of the viral proteins. Yet, the mechanisms by
      which Rex inhibits the cellular splicing machinery and utilizes the cellular
      pathways beneficial to viral survival in the host cell have not been fully
      explored. Furthermore, physiological impacts of Rex against homeostasis of the
      host cell via interactions with numerous cellular proteins have been largely left
      uninvestigated. In this review, we focus on the biological importance of HTLV-1
      Rex in the HTLV-1 life cycle by following the historical path in the literature
      concerning this viral post-transcriptional regulator from its discovery to this
      day. In addition, for future studies, we discuss recently discovered aspects of
      HTLV-1 Rex as a post-transcriptional regulator and its use in host cellular
      pathways.

PMID- 22973271
TI  - Defense peptides secreted by helminth pathogens: antimicrobial and/or
      immunomodulator molecules?
AB  - Host defense peptides (HDPs) are an evolutionarily conserved component of the
      innate immune response found in all living species. They possess antimicrobial
      activities against a broad range of organisms including bacteria, fungi,
      eukaryotic parasites, and viruses. HDPs also have the ability to enhance immune
      responses by acting as immunomodulators. We discovered a new family of HDPs
      derived from pathogenic helminth (worms) that cause enormous disease in animals
      and humans worldwide. The discovery of these peptides was based on their similar
      biochemical and functional characteristics to the human defense peptide LL-37. We
      propose that these new peptides modulate the immune response via molecular
      mimicry of mammalian HDPs thus providing a mechanism behind the anti-inflammatory
      properties of helminth infections.

PMID- 22973272
TI  - Emerging roles of eosinophils and eosinophil-derived lipid mediators in the
      resolution of inflammation.
AB  - Acute inflammation and its resolution are essential processes for tissue
      protection and homeostasis. Once thought to be a passive process, the resolution
      of inflammation is now shown to involve active biochemical programs that enable
      inflamed tissues to return to homeostasis. The mechanisms by which acute
      inflammation is resolved are of interest, and research in recent years has
      uncovered new endogenous anti-inflammatory and pro-resolving lipid mediators
      (i.e., lipoxins, resolvins, protectin, and maresin) generated from
      polyunsaturated fatty acids (PUFAs). This review presents new insights into the
      cellular and molecular mechanisms of inflammatory resolution, especially the
      roles of eosinophils, and a series of omega-3 PUFA-derived anti-inflammatory
      lipid mediators that they generate.

PMID- 22973273
TI  - The Serial Engagement Model 17 Years After: From TCR Triggering to Immunotherapy.
AB  - More than 15 years ago the serial engagement model was proposed as an attempt to
      solve the low affinity/high sensitivity paradox of TCR antigen recognition. Since
      then, the model has undergone ups and downs marked by the technical and
      conceptual advancements made in the field of T lymphocyte activation. Here, I
      describe the development of the model and survey recent literature providing
      evidence either for or against the idea that serial TCR/pMHC engagement might
      contribute to T lymphocyte activation. I also discuss how the concept of serial
      TCR engagement might be useful in the design of immunotherapeutic approaches
      aimed at potentiating T lymphocyte responses in vivo.

PMID- 22973274
TI  - Antimicrobial chemokines.
AB  - Chemokines are best known for their classic leukocyte chemotactic activity, which
      is critical for directing the immune response to sites of infection and injury.
      However, recent studies have suggested that at least some chemokines may also
      interfere with infectious agents directly. Antimicrobial chemokines tend to
      contain amphipathic alpha helical secondary structure, and broad-spectrum
      activity against both Gram-positive and Gram negative bacteria, as well as fungi.
      Conversely, several bacteria have been identified that possess mechanisms for
      specifically blocking the antimicrobial activities of chemokines. Although the
      precise mechanisms by which chemokines and microbes disarm one another in vitro
      remain unknown, there is now emerging evidence in vivo that such interactions may
      be biologically significant. More research will be needed to determine whether
      chemokines with direct antimicrobial activity may be translated into a novel
      class of antibiotics.

PMID- 22973275
TI  - Stromal cell contribution to human follicular lymphoma pathogenesis.
AB  - Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma
      displaying a strong dependence on a specialized cell microenvironment mimicking
      normal germinal center. Within malignant cell niches in invaded lymph nodes and
      bone marrow, external stimuli provided by infiltrating stromal cells make a
      pivotal contribution to disease development, progression, and drug resistance.
      The crosstalk between FL B cells and stromal cells is bidirectional, causing
      activation of both partners. In agreement, FL stromal cells exhibit specific
      phenotypic, transcriptomic, and functional properties. This review highlights the
      critical pathways involved in the direct tumor-promoting activity of stromal
      cells but also their role in the organization of FL cell niche through the
      recruitment of accessory immune cells and their polarization to a B cell
      supportive phenotype. Finally, deciphering the interplay between stromal cells
      and FL cells provides potential new therapeutic targets with the aim to mobilize
      malignant cells outside their protective microenvironment and increase their
      sensitivity to conventional treatment.

PMID- 22973276
TI  - Induction of Th17 cell differentiation by B-1 cells.
AB  - B-1 cells constitute a unique B cell population with distinct ontogenic,
      phenotypic, and functional characteristics. Naive, unmanipulated B-1 cells induce
      differentiation of CD4(+) T cells to become pro-inflammatory Th17 cells whereas
      naive B-2 cells do not. We examined the role of distinctly expressed surface
      membrane molecules in providing B-1 cells with Th17-differentiating function.
      Neither Mac-1, CD25, PD-L2 nor CD73 appeared to contribute to B-1 cell induction
      of Th17 differentiation. In contrast, we found that CD44 and CD86 are involved on
      the basis of studies with neutralizing antibodies and knock-out mice. Activation
      imparted to naive B-2 cells the ability to induce Th17 differentiation and this
      was similarly partially interrupted by interfering with CD44 and CD86. Our
      findings suggest that CD44-OPN and B7 family members play important roles in the
      induction of Th17 cell differentiation by B cells.

PMID- 22973277
TI  - Optical projection tomography reveals dynamics of HEV growth after immunization
      with protein plus CFA and features shared with HEVs in acute autoinflammatory
      lymphadenopathy.
AB  - The vascular-stromal compartment of lymph nodes is important for lymph node
      function, and high endothelial venules (HEVs) play a critical role in controlling
      the entry of recirculating lymphocytes. In autoimmune and autoinflammatory
      diseases, lymph node swelling is often accompanied by apparent HEV expansion and,
      potentially, targeting HEV expansion could be used therapeutically to limit
      autoimmunity. In previous studies using mostly flow cytometry analysis, we
      defined three differentially regulated phases of lymph node vascular-stromal
      growth: initiation, expansion, and the re-establishment of vascular quiescence
      and stabilization. In this study, we use optical projection tomography to better
      understand the morphologic aspects of HEV growth upon immunization with
      ovalbumin/CFA (OVA/CFA). We find HEV elongation as well as modest arborization
      during the initiation phase, increased arborization during the expansion phase,
      and, finally, vessel narrowing during the re-establishment of vascular quiescence
      and stabilization. We also examine acutely enlarged autoinflammatory lymph nodes
      induced by regulatory T cell depletion and show that HEVs are expanded and
      morphologically similar to the expanded HEVs in OVA/CFA-stimulated lymph nodes.
      These results reinforce the idea of differentially regulated, distinct phases of
      vascular-stromal growth after immunization and suggest that insights gained from
      studying immunization-induced lymph node vascular growth may help to understand
      how the lymph node vascular-stromal compartment could be therapeutically targeted
      in autoimmune and autoinflammatory diseases.

PMID- 22973278
TI  - Positive and negative regulation of T cell responses by fibroblastic reticular
      cells within paracortical regions of lymph nodes.
AB  - Fibroblastic reticular cells (FRC) form the structural backbone of the T cell
      rich zones in secondary lymphoid organs (SLO), but also actively influence the
      adaptive immune response. They provide a guidance path for immigrating T
      lymphocytes and dendritic cells (DC) and are the main local source of the
      cytokines CCL19, CCL21, and IL-7, all of which are thought to positively regulate
      T cell homeostasis and T cell interactions with DC. Recently, FRC in lymph nodes
      (LN) were also described to negatively regulate T cell responses in two distinct
      ways. During homeostasis they express and present a range of peripheral tissue
      antigens, thereby participating in peripheral tolerance induction of self
      reactive CD8(+) T cells. During acute inflammation T cells responding to foreign
      antigens presented on DC very quickly release pro-inflammatory cytokines such as
      interferon gamma. These cytokines are sensed by FRC which transiently produce
      nitric oxide (NO) gas dampening the proliferation of neighboring T cells in a non
      cognate fashion. In summary, we propose a model in which FRC engage in a
      bidirectional crosstalk with both DC and T cells to increase the efficiency of
      the T cell response. However, during an acute response, FRC limit excessive
      expansion and inflammatory activity of antigen-specific T cells. This negative
      feedback loop may help to maintain tissue integrity and function during rapid
      organ growth.

PMID- 22973279
TI  - DAMP signaling in fungal infections and diseases.
AB  - Fungal infections and diseases predominantly affect patients with deregulated
      immunity. Compelling experimental and clinical evidence indicate that severe
      fungal diseases belong to the spectrum of fungus-related inflammatory diseases.
      Some degree of inflammation is required for protection during the transitional
      response occurring temporally between the rapid innate and slower adaptive
      response. However, progressive inflammation worsens disease and ultimately
      prevents pathogen eradication. The challenge now is to elucidate cellular and
      molecular pathways distinguishing protective vs. pathogenic inflammation to
      fungi. In addition to fungal ligands of pattern recognition receptors (pathogen
      associated molecular patterns, PAMPs), several host-encoded proteins, the damage
      associated molecular patterns (DAMPs), are released during tissue injury and
      activate innate recognition receptors. DAMPs have been shown to regulate
      inflammation in fungal diseases. The DAMP/receptor for advanced glycation end
      products axis integrated with the PAMP/Toll-like receptors axis in the generation
      of the inflammatory response in experimental and clinical fungal pneumonia. These
      emerging themes better accommodate fungal pathogenesis in the face of high-level
      inflammation seen in several clinical settings and point to DAMP targeting as a
      novel immunomodulatory strategy in fungal diseases.

PMID- 22973280
TI  - RNA transport during TMV cell-to-cell movement.
AB  - Studies during the last 25 years have provided increasing evidence for the
      ability of plants to support the cell-to-cell and systemic transport of RNA
      molecules and that this process plays a role in plant development and in the
      systemic orchestration of cellular responses against pathogens and other
      environmental challenges. Since RNA viruses exploit the cellular RNA transport
      machineries for spreading their genomes between cells they represent convenient
      models to investigate the underlying mechanisms. In this regard, the
      intercellular spread of Tobacco mosaic virus (TMV) has been studied for many
      years. The RNA of TMV moves cell-to-cell in a non-encapsidated form in a process
      depending on virus-encoded movement protein (MP). Here, we discuss the current
      state of the art in studies using TMV and its MP as a model for RNA transport.
      While the ability of plants to transport viral and cellular RNA molecules is
      consistent with RNA transport phenomena in other systems, further studies are
      needed to increase our ability to visualize viral RNA (vRNA) in vivo and to
      distinguish RNA-transport related processes from those involved in antiviral
      defense.

PMID- 22973282
TI  - How Can the Light Reactions of Photosynthesis be Improved in Plants?

PMID- 22973283
TI  - A High-Throughput Method for Illumina RNA-Seq Library Preparation.
AB  - With the introduction of cost effective, rapid, and superior quality next
      generation sequencing techniques, gene expression analysis has become viable for
      labs conducting small projects as well as large-scale gene expression analysis
      experiments. However, the available protocols for construction of RNA-sequencing
      (RNA-Seq) libraries are expensive and/or difficult to scale for high-throughput
      applications. Also, most protocols require isolated total RNA as a starting
      point. We provide a cost-effective RNA-Seq library synthesis protocol that is
      fast, starts with tissue, and is high-throughput from tissue to synthesized
      library. We have also designed and report a set of 96 unique barcodes for library
      adapters that are amenable to high-throughput sequencing by a large combination
      of multiplexing strategies. Our developed protocol has more power to detect
      differentially expressed genes when compared to the standard Illumina protocol,
      probably owing to less technical variation amongst replicates. We also address
      the problem of gene-length biases affecting differential gene expression calls
      and demonstrate that such biases can be efficiently minimized during mRNA
      isolation for library preparation.

PMID- 22973281
TI  - Conserved and plant-unique mechanisms regulating plant post-Golgi traffic.
AB  - Membrane traffic plays crucial roles in diverse aspects of cellular and organelle
      functions in eukaryotic cells. Molecular machineries regulating each step of
      membrane traffic including the formation, tethering, and fusion of membrane
      carriers are largely conserved among various organisms, which suggests that the
      framework of membrane traffic is commonly shared among eukaryotic lineages.
      However, in addition to the common components, each organism has also acquired
      lineage-specific regulatory molecules that may be associated with the lineage
      specific diversification of membrane trafficking events. In plants, comparative
      genomic analyses also indicate that some key machineries of membrane traffic are
      significantly and specifically diversified. In this review, we summarize recent
      progress regarding plant-unique regulatory mechanisms for membrane traffic, with
      a special focus on vesicle formation and fusion components in the post-Golgi
      trafficking pathway.

PMID- 22973284
TI  - AT_CHLORO: A Chloroplast Protein Database Dedicated to Sub-Plastidial
      Localization.
AB  - AT_CHLORO (www.grenoble.prabi.fr/at_chloro) is a database dedicated to sub
      plastidial localization of A. thaliana chloroplast proteins. This information was
      infered from proteomics experiments obtained from a comprehensive study that
      allowed the identification of proteins from envelope, stroma, and thylakoid sub
      compartments Ferro et al., 2010. In addition to current knowledge regarding sub
      plastidial localization, AT_CHLORO provides experimental data that allowed
      curated information regarding subcellular localizations of chloroplast proteins
      to be given. A specific focus was given to proteins that were identified in
      envelope fractions and for which expert functional annotation was provided. The
      present mini review shows the specificities of AT_CHLORO with respect to
      available information, data export options and recent improvements in data
      representation.

PMID- 22973285
TI  - P(3)DB: An Integrated Database for Plant Protein Phosphorylation.
AB  - Protein phosphorylation is widely recognized as the most widespread, enzyme
      catalyzed post-translational modification in eukaryotes. In particular, plants
      have appropriated this signaling mechanism as evidenced by the twofold higher
      frequency of protein kinases within the genome compared to other eukaryotes.
      While all aspects of plant protein phosphorylation research have grown in the
      past 10 years; phosphorylation site mapping using high-resolution mass
      spectrometry has grown exponentially. In Arabidopsis alone there are thousands of
      experimentally determined phosphorylation sites. To archive these events in a
      user-intuitive format we have developed P(3)DB, the Plant Protein Phosphorylation
      Database (p3db.org). This database is a repository for plant protein
      phosphorylation site data, currently hosting information on 32,963 non-redundant
      sites collated from 23 experimental studies from six plant species. These data
      can be queried for a protein-of-interest using an integrated BLAST module to
      query similar sequences with known phosphorylation sites among the multiple
      plants currently investigated. The paper demonstrates how this resource can help
      identify functionally conserved phosphorylation sites in plants using a multi
      system approach.

PMID- 22973286
TI  - Characterization and Prediction of Protein Phosphorylation Hotspots in
      Arabidopsis thaliana.
AB  - The regulation of protein function by modulating the surface charge status via
      sequence-locally enriched phosphorylation sites (P-sites) in so called
      phosphorylation "hotspots" has gained increased attention in recent years. We set
      out to identify P-hotspots in the model plant Arabidopsis thaliana. We analyzed
      the spacing of experimentally detected P-sites within peptide-covered regions
      along Arabidopsis protein sequences as available from the PhosPhAt database.
      Confirming earlier reports (Schweiger and Linial, 2010), we found that, indeed, P
      sites tend to cluster and that distributions between serine and threonine P-sites
      to their respected closest next P-site differ significantly from those for
      tyrosine P-sites. The ability to predict P-hotspots by applying available
      computational P-site prediction programs that focus on identifying single P-sites
      was observed to be severely compromised by the inevitable interference of nearby
      P-sites. We devised a new approach, named HotSPotter, for the prediction of
      phosphorylation hotspots. HotSPotter is based primarily on local amino acid
      compositional preferences rather than sequence position-specific motifs and uses
      support vector machines as the underlying classification engine. HotSPotter
      correctly identified experimentally determined phosphorylation hotspots in A.
      thaliana with high accuracy. Applied to the Arabidopsis proteome, HotSPotter
      predicted 13,677 candidate P-hotspots in 9,599 proteins corresponding to 7,847
      unique genes. Hotspot containing proteins are involved predominantly in signaling
      processes confirming the surmised modulating role of hotspots in signaling and
      interaction events. Our study provides new bioinformatics means to identify
      phosphorylation hotspots and lays the basis for further investigating novel
      candidate P-hotspots. All phosphorylation hotspot annotations and predictions
      have been made available as part of the PhosPhAt database at
      http://phosphat.mpimp-golm.mpg.de.

PMID- 22973287
TI  - Identification and characterization of orthologs of AtNHX5 and AtNHX6 in Brassica
      napus.
AB  - Improving crop species by breeding for salt tolerance or introducing salt
      tolerant traits is one method of increasing crop yields in saline affected areas.
      Extensive studies of the model plant species Arabidopsis thaliana has led to the
      availability of substantial information regarding the function and importance of
      many genes involved in salt tolerance. However, the identification and
      characterization of A. thaliana orthologs in species such as Brassica napus
      (oilseed rape) can prove difficult due to the significant genomic changes that
      have occurred since their divergence approximately 20 million years ago (MYA).
      The recently released Brassica rapa genome provides an excellent resource for
      comparative studies of A. thaliana and the cultivated Brassica species, and
      facilitates the identification of Brassica species orthologs which may be of
      agronomic importance. Sodium hydrogen antiporter (NHX) proteins transport a
      sodium or potassium ion in exchange for a hydrogen ion in the other direction
      across a membrane. In A. thaliana there are eight members of the NHX family,
      designated AtNHX1-8, that can be sub-divided into three clades, based on their
      subcellular localization: plasma membrane (PM), intracellular class I (IC-I) and
      intracellular class II (IC-II). In plants, many NHX proteins are primary
      determinants of salt tolerance and act by transporting Na(+) out of the cytosol
      where it would otherwise accumulate to toxic levels. Significant work has been
      done to determine the role of both PM and IC-I clade members in salt tolerance in
      a variety of plant species, but relatively little analysis has been described for
      the IC-II clade. Here we describe the identification of B. napus orthologs of
      AtNHX5 and AtNHX6, using the B. rapa genome sequence, macro- and micro-synteny
      analysis, comparative expression and promoter motif analysis, and highlight the
      value of these multiple approaches for identifying true orthologs in closely
      related species with multiple paralogs.

PMID- 22973288
TI  - Functional genomics tools applied to plant metabolism: a survey on plant
      respiration, its connections and the annotation of complex gene functions.
AB  - The application of post-genomic techniques in plant respiration studies has
      greatly improved our ability to assign functions to gene products. In addition it
      has also revealed previously unappreciated interactions between distal elements
      of metabolism. Such results have reinforced the need to consider plant
      respiratory metabolism as part of a complex network and making sense of such
      interactions will ultimately require the construction of predictive and
      mechanistic models. Transcriptomics, proteomics, metabolomics, and the
      quantification of metabolic flux will be of great value in creating such models
      both by facilitating the annotation of complex gene function, determining their
      structure and by furnishing the quantitative data required to test them. In this
      review, we highlight how these experimental approaches have contributed to our
      current understanding of plant respiratory metabolism and its interplay with
      associated process (e.g., photosynthesis, photorespiration, and nitrogen
      metabolism). We also discuss how data from these techniques may be integrated,
      with the ultimate aim of identifying mechanisms that control and regulate plant
      respiration and discovering novel gene functions with potential biotechnological
      implications.

PMID- 22973289
TI  - Plant-Specific Myosin XI, a Molecular Perspective.
AB  - In eukaryotic cells, organelle movement, positioning, and communications are
      critical for maintaining cellular functions and are highly regulated by
      intracellular trafficking. Directional movement of motor proteins along the
      cytoskeleton is one of the key regulators of such trafficking. Most plants have
      developed a unique actin-myosin system for intracellular trafficking. Although
      the composition of myosin motors in angiosperms is limited to plant-specific
      myosin classes VIII and XI, there are large families of myosins, especially in
      class XI, suggesting functional diversification among class XI members. However,
      the molecular properties and regulation of each myosin XI member remains unclear.
      To achieve a better understanding of the plant-specific actin-myosin system, the
      characterization of myosin XI members at the molecular level is essential. In the
      first half of this review, we summarize the molecular properties of tobacco 175
      kDa myosin XI, and in the later half, we focus on myosin XI members in
      Arabidopsis thaliana. Through detailed comparison of the functional domains of
      these myosins with the functional domain of myosin V, we look for possible
      diversification in enzymatic and mechanical properties among myosin XI members
      concomitant with their regulation.

PMID- 22973290
TI  - Exploring the shallow end; estimating information content in transcriptomics
      studies.
AB  - Transcriptomics is a major platform to study organismal biology. The advent of
      new parallel sequencing technologies has opened up a new avenue of
      transcriptomics with ever deeper and deeper sequencing to identify and quantify
      each and every transcript in a sample. However, this may not be the best usage of
      the parallel sequencing technology for all transcriptomics experiments. I
      utilized the Shannon Entropy approach to estimate the information contained
      within a transcriptomics experiment and tested the ability of shallow RNAseq to
      capture the majority of this information. This analysis showed that it was
      possible to capture nearly all of the network or genomic information present in a
      variety of transcriptomics experiments using a subset of the most abundant 5000
      transcripts or less within any given sample. Thus, it appears that it should be
      possible and affordable to conduct large scale factorial analysis with a high
      degree of replication using parallel sequencing technologies.

PMID- 22973291
TI  - Priming against environmental challenges and proteomics in plants: Update and
      agricultural perspectives.
AB  - Priming is the cellular state in which the harmful effects of abiotic stress
      factors in plants are hindered by pre-exposure to a stimulus, thus resulting in
      greater survival. It is becoming increasingly evident that priming techniques
      (e.g., external application of natural or synthetic compounds in plants) can
      enhance the tolerance of crops to environmental stresses. Innovative systems
      biology approaches such as proteomics are currently recognized as essential tools
      to understand the molecular mechanisms underlying plant responses to
      environmental stimuli and priming phenomena. The few published proteomic studies
      on priming in the context of environmental stress identify key protein targets
      and signaling pathways which are being involved in the alleviation of negative
      effects of stress factors. Since priming is a very promising strategy in modern
      crop production management, further research is needed in order to establish the
      global picture of priming phenomena against environmental challenges as well as
      to characterize specific priming-related protein indicators in plants.

PMID- 22973292
TI  - Negligible senescence.

PMID- 22973293
TI  - Aging: the fading signal of natural selection.

PMID- 22973294
TI  - Gene expression in late-life.

PMID- 22973295
TI  - Identification of Identical Transcript Changes in Liver and Whole Blood during
      Acetaminophen Toxicity.
AB  - The ability to identify mechanisms underlying drug-induced liver injury (DILI) in
      man has been hampered by the difficulty in obtaining liver tissue from patients.
      It has recently been proposed that whole blood toxicogenomics may provide a non
      invasive means for mechanistic studies of human DILI. However, it remains unclear
      to what extent changes in whole blood transcriptome mirror those in liver
      mechanistically linked to hepatotoxicity. To address this question, we applied
      the program Extracting Patterns and Identifying co-expressed Genes (EPIG) to
      publically available toxicogenomic data obtained from rats treated with both
      toxic and subtoxic doses of acetaminophen (APAP). In a training set of animals,
      we identified genes (760 at 6 h and 185 at 24 h post dose) with similar patterns
      of expression in blood and liver during APAP-induced hepatotoxicity. The pathways
      represented in the coordinately regulated genes largely involved mitochondrial
      and immune functions. The identified expression signatures were then evaluated in
      a separate set of animals for discernment of APAP exposure level or APAP-induced
      hepatotoxicity. At 6 h, the gene sets from liver and blood had equally sufficient
      classification of APAP exposure levels. At 24 h when toxicity was evident, the
      gene sets did not perform well in evaluating APAP exposure doses, but provided
      accurate classification of dose-independent liver injury that was evaluated by
      serum ALT elevation in the blood. Only 38 genes were common to both the 6 and 24
      h gene sets, but these genes had the same capability as the parent gene sets to
      discern the exposure level and degree of liver injury. Some of the parallel
      transcript changes reflect pathways that are relevant to APAP hepatotoxicity,
      including mitochondria and immune functions. However, the extent to which these
      changes reflect similar mechanisms of action in both tissues remains to be
      determined.

PMID- 22973296
TI  - Benefits of using molecular structure and abundance in phylogenomic analysis.

PMID- 22973297
TI  - Localization of association signal from risk and protective variants in
      sequencing studies.
AB  - Aggregating information across multiple variants in a gene or region can improve
      power for rare variant association testing. Power is maximized when the
      aggregation region contains many causal variants and few neutral variants. In
      this paper, we present a method for the localization of the association signal in
      a region using a sliding-window based approach to rare variant association
      testing in a region. We first introduce a novel method for analysis of rare
      variants, the Difference in Minor Allele Frequency test (DMAF), which allows
      combined analysis of common and rare variants, and makes no assumptions about the
      direction of effects. In whole-region analyses of simulated data with risk and
      protective variants, DMAF and other methods which pool data across individuals
      were found to outperform methods which pool data across variants. We then
      implement a sliding-window version of DMAF, using a step-down permutation
      approach to control type I error with the testing of multiple windows. In
      simulations, the sliding-window DMAF improved power to detect a causal sub
      region, compared to applying DMAF to the whole region. Sliding-window DMAF was
      also effective in localizing the causal sub-region. We also applied the DMAF
      sliding-window approach to test for an association between response to the drug
      gemcitabine and variants in the gene FKBP5 sequenced in 91 lymphoblastoid cell
      lines derived from white non-Hispanic individuals. The application of the sliding
      window test procedure detected an association in a sub-region spanning an exon
      and two introns, when rare and common variants were analyzed together.

PMID- 22973298
TI  - Translesion DNA polymerases and cancer.
AB  - DNA repair has been regarded as an important barrier to carcinogenesis. The newly
      discovered field of translesion synthesis (TLS) has made it apparent that
      mammalian cells need distinct polymerases to efficiently and accurately bypass
      DNA lesions. Perturbation of TLS polymerase activity by mutation, loss of
      expression, etc. is expected to result in the accumulation of mutations in cells
      exposed to specific carcinogens. Furthermore, several TLS polymerases can
      modulate cellular sensitivity to chemotherapeutic agents. TLS genes and TLS gene
      variations may thus be attractive pharmacologic and/or pharmacogenetic targets.
      We review herein current data with regards to the potential contribution of the
      primary TLS polymerase genes to cancer, their interaction with pharmacologic
      agents, and identify areas of interest for further research.

PMID- 22973299
TI  - Updating our view of organelle genome nucleotide landscape.
AB  - Organelle genomes show remarkable variation in architecture and coding content,
      yet their nucleotide composition is relatively unvarying across the eukaryotic
      domain, with most having a high adenine and thymine (AT) content. Recent studies,
      however, have uncovered guanine and cytosine (GC)-rich mitochondrial and plastid
      genomes. These sequences come from a small but eclectic list of species,
      including certain green plants and animals. Here, I review GC-rich organelle DNAs
      and the insights they have provided into the evolution of nucleotide landscape. I
      emphasize that GC-biased mitochondrial and plastid DNAs are more widespread than
      once thought, sometimes occurring together in the same species, and suggest that
      the forces biasing their nucleotide content can differ both among and within
      lineages, and may be associated with specific genome architectural features and
      life history traits.

PMID- 22973300
TI  - Bayesian methods for multivariate modeling of pleiotropic SNP associations and
      genetic risk prediction.
AB  - Genome-wide association studies (GWAS) have identified numerous associations
      between genetic loci and individual phenotypes; however, relatively few GWAS have
      attempted to detect pleiotropic associations, in which loci are simultaneously
      associated with multiple distinct phenotypes. We show that pleiotropic
      associations can be directly modeled via the construction of simple Bayesian
      networks, and that these models can be applied to produce single or ensembles of
      Bayesian classifiers that leverage pleiotropy to improve genetic risk prediction.
      The proposed method includes two phases: (1) Bayesian model comparison, to
      identify Single-Nucleotide Polymorphisms (SNPs) associated with one or more
      traits; and (2) cross-validation feature selection, in which a final set of SNPs
      is selected to optimize prediction. To demonstrate the capabilities and
      limitations of the method, a total of 1600 case-control GWAS datasets with two
      dichotomous phenotypes were simulated under 16 scenarios, varying the association
      strengths of causal SNPs, the size of the discovery sets, the balance between
      cases and controls, and the number of pleiotropic causal SNPs. Across the 16
      scenarios, prediction accuracy varied from 90 to 50%. In the 14 scenarios that
      included pleiotropically associated SNPs, the pleiotropic model search and
      prediction methods consistently outperformed the naive model search and
      prediction. In the two scenarios in which there were no true pleiotropic SNPs,
      the differences between the pleiotropic and naive model searches were minimal. To
      further evaluate the method on real data, a discovery set of 1071 sickle cell
      disease (SCD) patients was used to search for pleiotropic associations between
      cerebral vascular accidents and fetal hemoglobin level. Classification was
      performed on a smaller validation set of 352 SCD patients, and showed that the
      inclusion of pleiotropic SNPs may slightly improve prediction, although the
      difference was not statistically significant. The proposed method is robust,
      computationally efficient, and provides a powerful new approach for detecting and
      modeling pleiotropic disease loci.

PMID- 22973301
TI  - Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to
      sequential disruption of mTORC1 and mTORC2.
AB  - Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity
      in acute studies in vitro and in vivo by disrupting a negative feedback loop
      mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on
      insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the
      first hour that declines to almost complete insulin resistance by 24-48 h. We and
      others have recently observed that chronic rapamycin treatment induces insulin
      resistance in rodents, at least in part due to disruption of mTORC2, an mTOR
      containing complex that is not acutely sensitive to the drug. Chronic rapamycin
      treatment may also impair insulin action via the inhibition of mTORC1-dependent
      mitochondrial biogenesis and activity, which could result in a buildup of lipid
      intermediates that are known to trigger insulin resistance. We confirmed that
      rapamycin inhibits expression of PGC-1alpha, a key mitochondrial transcription
      factor, and acutely reduces respiration rate in myotubes. However, rapamycin did
      not stimulate phosphorylation of PKCtheta, a central mediator of lipid-induced
      insulin resistance. Instead, we found dramatic disruption of mTORC2, which
      coincided with the onset of insulin resistance. Selective inhibition of mTORC1 or
      mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor,
      respectively) confirmed that mitochondrial effects of rapamycin are mTORC1
      dependent, whereas insulin resistance was recapitulated only by knockdown of
      mTORC2. Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes
      insulin resistance in rapamycin-treated myotubes, and this system may serve as a
      useful model to understand the effects of rapamycin on mTOR signaling in vivo.

PMID- 22973302
TI  - Bioinformatic challenges of big data in non-coding RNA research.

PMID- 22973303
TI  - MeCP2 as a genome-wide modulator: the renewal of an old story.
AB  - Since the discovery of MeCP2, its functions have attracted the interest of
      generations of molecular biologists. Its function as a transducer of DNA
      methylation, the major post-biosynthetic modification found throughout genomes,
      and its association with the neurodevelopmental disease Rett syndrome highlight
      its central role as a transcriptional regulator, and, at the same time, poses
      puzzling questions concerning its roles in physiology and pathology. The
      classical model of the MeCP2 function predicts its role in gene-specific
      repression through the binding of methylated DNA, via its interaction with the
      histone deacetylases and co-repressor complexes. This view has been questioned
      and, intriguingly, new roles for MeCP2 as a splicing modulator and as a
      transcriptional activator have been proposed. Recent data have demonstrated that
      MeCP2 is extremely abundant in the neurons, where it reaches the level of histone
      H1; it is widely distributed, tracking the methylated CpGs, and regulates
      repetitive elements expression. The role of MeCP2 in maintaining the global
      chromatin structure is further sustained by its involvement in other biologically
      relevant phenomena, such as the Line-1 repetitive sequences retrotransposition
      and the pericentromeric heterochromatin clustering during cellular
      differentiation. These new concepts renew the old view suggesting a role for DNA
      methylation in transcriptional noise reduction, pointing to a key role for MeCP2
      in the modulation of the genome architecture.

PMID- 22973305
TI  - Repeated Liver Resection for Colorectal Liver Metastases: A Comparison with
      Primary Liver Resections concerning Perioperative and Long-Term Outcome.
AB  - Introduction. 60% of patients operated for colorectal liver metastases (CRLM)
      will develop recurrent disease and some may be candidates for a repeated liver
      resection. The study aimed to evaluate differences in intraoperative blood loss
      and complications comparing the primary and the repeated liver resection for
      metastases of colorectal cancer (CRC), as well as to evaluate differences in long
      time follow-up. Method. 32 patients underwent 34 repeated liver resections due to
      recurrence of CRLM an studied retrospectively to identify potential differences
      between the primary and the repeat resections. Results. There was no 30-day
      postoperative mortality or postoperative hospital deaths. The median blood loss
      at repeat resection (1850 mL) was significantly (P = 0.014) higher as compared to
      the primary liver resection (1000 mL). This did not have any effect on the rate
      of complications, even though increased bleeding in itself was a risk factor for
      complications. There were no differences in survival at long-term follow-up.
      Discussion. A repeated liver resection for CRLM was associated with an increased
      intraoperative bleeding as compared to the first resection. Possible explanations
      include presence of adhesions, deranged vascular anatomy, more complicated
      operations and the effects on the liver by chemotherapy following the first liver
      resection. 30 out of 32 patients had only one reresection of the liver.

PMID- 22973306
TI  - On the dynamics of active aging.
AB  - The conceptual basis of active aging is extended with a dynamic systems model,
      called Janus. The Janus model accounts for the life-course dynamics of simple and
      more complex growth and decline functions, on the strength of three principles.
      The first principle of transition states that the unitary lifespan trajectory of
      development and aging is the product of two complementary forces, growth and
      senescence, which are effective from conception until death. The first principle
      solves the traditional problem of the age at which development ends and the
      process of aging starts. The second and third principles of peak capacity and
      peak time refer, respectively, to the impact of growth rate (peak capacity) and
      rate of senescence (peak time) on the life-course of dynamic systems. The
      validity of the Janus model is demonstrated by simulating the empirical lifespan
      trajectories of functional capacity, intelligence, and mortality. The Janus model
      contributes to the concept of active aging by underlining the dynamic limits of
      human nature, by stimulating effective policies for promoting active aging in the
      first half of life, and by emphasizing the growth potential of older people in
      the second half.

PMID- 22973304
TI  - Vascular disease in diabetic women: Why do they miss the female protection?
AB  - Gender plays a pivotal role in the onset as well as in the progression of the
      cardiovascular disease with a higher morbidity and mortality being detected in
      men with respect to women. Type 2 Diabetes Mellitus (T2DM) may reduce gender
      related differences in the prevalence of cardiovascular disease by fading the
      vascular protective effects afforded by estrogen in females. This article will
      discuss the role of sex and sex hormones on the incidence and mechanisms involved
      in vascular dysfunction associated to T2DM, which might explain why women with
      T2DM lack the vascular protection.

PMID- 22973307
TI  - Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL
      Recognition.
AB  - Pseudomonas aeruginosa is the most common pathogen that persists in the cystic
      fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron
      chelating molecules) and the host limits bacterial growth by producing neutrophil
      gelatinase-associated lipocalin (NGAL) that specifically scavenges bacterial
      siderophores, therefore preventing bacteria from establishing infection. P.
      aeruginosa produces a major siderophore known as pyoverdine, found to be
      important for bacterial virulence and biofilm development. We report that
      pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence
      quenching, while enterobactin bound to NGAL effectively causing a strong
      response. The experimental data indicate that pyoverdine evades NGAL recognition.
      We then employed a molecular modeling approach to simulate the binding of
      pyoverdine to human NGAL using NGAL's published crystal structures. The docking
      of pyoverdine to NGAL predicted nine different docking positions; however,
      neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site
      in the calyx of NGAL where siderophores are known to bind. The molecular modeling
      results offer structural support that pyoverdine does not bind to NGAL,
      confirming the results obtained in the tryptophan quenching assay. The data
      suggest that pyoverdine is a stealth siderophore that evades NGAL recognition
      allowing P. aeruginosa to establish chronic infections in CF lungs.

PMID- 22973308
TI  - Free Triiodothyronine and Cholesterol Levels in Euthyroid Elderly T2DM Patients.
AB  - Thyroid function regulates lipid metabolism. Despite the fact that T2DM is more
      prevalent in the elderly, often associates with thyroid dysfunction and increases
      cardiovascular risk both per se and via high TC and LDL-C levels, the association
      of the latter with FT(3) and FT(4) levels has not yet been fully investigated in
      T2DM. While trying to fill this gap in 296 elderly outpatients with T2DM, we
      found that TC and LDL-C correlated negatively with FT(4) and positively with
      FT(3). When divided according to treatment by oral hypoglycaemic agents (OHA) and
      insulin (IT), they reacted differently with respect to investigated associations:
      in the OHA's TC and LDL-C correlated negatively with FT(4) and showed no
      association with FT(3), whereas, in the IT's TC and LDL-C correlated positively
      with FT(3) and negatively with FT(4). When controlled for possible confounding
      factors, these associations did not change in the IT's but were missing in the
      OHA's. Recent literature reports upon complex hypothalamic and peripheral
      interactions between T2DM and thyroid, and suggests T(3) to enhance cholesterol
      synthesis and to have a role in insulin resistance states. Further investigations
      are needed to understand the intimate mechanisms of lipid metabolism in T2DM with
      respect to thyroid function.

PMID- 22973310
TI  - PET Tracers for Clinical Imaging of Breast Cancer.
AB  - Molecular imaging of breast cancer has undoubtedly permitted a substantial
      development of the overall diagnostic accuracy of this malignancy in the last
      years. Accurate tumour staging, design of individually suited therapies, response
      evaluation, early detection of recurrence and distant lesions have also evolved
      in parallel with the development of novel molecular imaging approaches. In this
      context, positron emission tomography (PET) can be probably seen as the most
      interesting molecular imaging technology with straightforward clinical
      application for such purposes. Dozens of radiotracers for PET imaging of breast
      cancer have been tested in laboratory animals. However, in this review we shall
      focus mainly in the smaller group of PET radiopharmaceuticals that have lead
      through into the clinical setting. PET imaging can be used to target general
      metabolic phenomena related to tumoural transformation, including glucose
      metabolism and cell proliferation, but can also be directed to specific hormone
      receptors that are characteristic of the breast cancer cell. Many other receptors
      and transport molecules present in the tumour cells could also be of interest for
      imaging. Furthermore, molecules related with the tumour microenvironment, tumour
      induced angiogenesis or even hypoxia could also be used as molecular biomarkers
      for breast cancer imaging.

PMID- 22973311
TI  - Use of ICDAS-II, Fluorescence-Based Methods, and Radiography in Detection and
      Treatment Decision of Occlusal Caries Lesions: An In Vitro Study.
AB  - Aim. To use visual inspection (ICDAS-II), laser fluorescence (LF), fluorescence
      based camera (FC) and radiographic examination (BW) for detection of caries and
      for treatment decision. Methods. The occlusal sites of 84 extracted permanent
      teeth were examined using all methods and treatment decisions (preventive or
      operative care) were recorded based on each method independently. For validation
      of the findings, fissures were opened with rotating instruments and clinical
      depth was determined as gold standard. Correlations (r(s)), sensitivity,
      specificity and AUC were calculated. McNemar test was used to show whether
      different methods led to significant changes in treatment decisions. Results.
      Highest correlation was found between ICDAS-II and FC (r(s) 0.84), ICDAS-II and
      gold standard (0.82) and FC and gold standard (0.81). ICDAS-II provided the
      highest performance (AUC 1.0), followed by FC (0.95) and LF (0.88). The greatest
      difference was found for treatment planning of dentine lesions, where the use of
      FC (cut-offs according to the literature) had the greatest agreement between
      operative treatment and dentine lesions, followed by use of ICDAS-II. Conclusion.
      ICDAS-II may have high potential for detection and treatment planning, and other
      devices, especially the fluorescence camera, can add substantial information to
      the visual examination, enabling examiners plan treatment more accurately.

PMID- 22973309
TI  - Glioma revisited: from neurogenesis and cancer stem cells to the epigenetic
      regulation of the niche.
AB  - Gliomas are the most incident brain tumor in adults. This malignancy has very low
      survival rates, even when combining radio- and chemotherapy. Among the gliomas,
      glioblastoma multiforme (GBM) is the most common and aggressive type, and
      patients frequently relapse or become refractory to conventional therapies. The
      fact that such an aggressive tumor can arise in such a carefully orchestrated
      organ, where cellular proliferation is barely needed to maintain its function, is
      a question that has intrigued scientists until very recently, when the discovery
      of the existence of proliferative cells in the brain overcame such challenges.
      Even so, the precise origin of gliomas still remains elusive. Thanks to new
      advents in molecular biology, researchers have been able to depict the first
      steps of glioma formation and to accumulate knowledge about how neural stem cells
      and its progenitors become gliomas. Indeed, GBM are composed of a very
      heterogeneous population of cells, which exhibit a plethora of tumorigenic
      properties, supporting the presence of cancer stem cells (CSCs) in these tumors.
      This paper provides a comprehensive analysis of how gliomas initiate and
      progress, taking into account the role of epigenetic modulation in the crosstalk
      of cancer cells with their environment.

PMID- 22973312
TI  - Prevalence and reasons for tooth loss in a sample from a dental clinic in Brazil.
AB  - Purpose. To evaluate the prevalence and reasons for teeth extractions in a sample
      from a dental clinic in Brazil. Methods. The prevalence of teeth mortality was
      analyzed by gender, age, tooth type and reasons for extraction on 800 teeth of
      439 subjects, whose data was collected in clinical records in a convenience
      sample. Results. The groups with range from 35 to 44 years, 45 to 54 years and 55
      to 64 years revealed significantly greater number of teeth extractions than other
      age groups (P < 0.0001). The anterior teeth loss increased significantly with
      aging, while the tooth mortality of premolar and molar were higher in younger
      people. The caries was the more prevalent reason for tooth mortality among young
      and adults up to 44 years old, while the periodontal disease was the main reason
      for extractions from 45 years old until range of 81 years (P < 0.0001).
      Conclusions. It can be suggested that some reasons for tooth loss were age
      dependent, but the caries and the periodontal diseases were the main reasons for
      tooth mortality in this Brazilian sample.

PMID- 22973313
TI  - Xenograft enriched with autologous bone marrow in inlay reconstructions: a
      tomographic and histomorphometric study in rabbit calvaria.
AB  - Objective. The aim of this study was to evaluate the bone healing after the usage
      of a scaffold enriched with bone marrow. Study Design. Ten rabbits were divided
      into 2 groups of 5 animals. Bilateral 12 mm diameter defects were created in the
      parietal bones. In control group Bio-Oss were inserted in both defects and, in
      experimental group, Bio-Oss enriched with autologous bone marrow were inserted in
      both defects. In these two groups, one of the calvarial defects was covered with
      Bio-Gide. The rabbits were sacrified 8 weeks after surgery and both CT and
      histomorphometric analysis were done. Results. The CT showed a lower remaining
      defect area in the experimental group covered with Bio-Gide when compared with
      control group, with and without Bio-Gide. The histomorphometrics showed no
      difference between groups regarding the non-vital mineralized tissue area. For
      vital mineralized tissue area, the experimental group covered with Bio-Gide
      obtained a higher percentage area when compared with control group, with and
      without Bio-Gide. For non-mineralized tissue area, the experimental group covered
      with Bio-Gide obtained a lower percentage area when compared with control group,
      with and without Bio-Gide. Conclusion. Both autologous bone marrow and membrane
      can contribute to the enhancement of bone healing.

PMID- 22973315
TI  - Rapid multiorgan dissemination of low-grade myxofibrosarcoma: a case report.
AB  - Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly
      people. It is characterized by a high frequency of local recurrence due to an
      infiltrative growth property. In contrast, the overall risk of distant metastases
      is generally low. This makes the prognosis for the patients with myxofibrosarcoma
      definitely good. In this paper, we will report the case of a 79-year-old female
      with very aggressive metastatic low-grade myxofibrosarcoma. The disease
      progression was really unexpected and misled every possible medical
      interpretation, leading to rapid worsening of the patient's clinical conditions
      and no chance for therapy. The tumor developed diffuse infiltration in lung,
      spine, skeletal bone, abdomen, paravertebral muscles, and liver. The patient died
      8 months after the diagnosis of remote metastases due to rapid tumor progression.

PMID- 22973316
TI  - Unusual location of primary hydatid cyst: soft tissue mass in the supraclavicular
      region of the neck.
AB  - Cystic hydatid disease is a zoonosis caused by Echinococcus granulosus. It may
      affect any organ and tissue in the body, in particular the liver and Lung.
      Musculoskeletal or soft tissue hydatidosis accounts for about 0,5%-5% of all
      echinococcal infections in endemic areas and is almost secondary to the hepatic
      or pulmonary disease (Karaman et al., 2011; Dirican et al., 2008; Kouskos et al.,
      2007). Case Presentation. We report an unusual case of primary subcutaneous
      hydatidosis in the left supraclavicular region of the neck. A 53-year-old female
      patient was admitted with three-month history of pain and gradually growing mass
      located in the left supraclavicular region. Physical examination revealed a
      moderately hard, painful, and erythematous mass. The blood cell count was normal.
      Computed tomography demonstrated, a multilocular cystic lesion with thin borders
      and thin wall. The mass is binocular and extends to the scapula. CT showed no
      involvement of the lung. From these signs, the patient was diagnosed as having
      abscess (bacterial infection or tuberculosis). The diagnosis of Echinococcus
      granulosus infection was made per operatively after visualization of the cyst
      wall and the daughter cysts. Following irrigation of cystic cavity with
      hypertonic saline solution, the cyst wall was excised along with a portion of
      surrounding tissue. Histopathological examination of the specimen confirmed the
      hydatid origin. Hemagglutination tests for Echinococcus and ELISA were negative.
      Ultrasound of the abdomen was normal. The patient received albendazole (400
      mg/day) for 8 weeks postoperatively. No sign of recurrence could be detected by
      physical examination and imaging (CT) at 4-month followup. Conclusion. The case
      illustrates that echinococcal disease should be considered in the differential
      diagnosis of every cystic mass in every anatomic location, especially when it
      occurs in endemic areas.

PMID- 22973314
TI  - Brain miffed by macrophage migration inhibitory factor.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine which also exhibits
      enzymatic properties like oxidoreductase and tautomerase. MIF plays a pivotal
      role in innate and acquired immunity as well as in the neuroendocrine axis. Since
      it is involved in the pathogenesis of acute and chronic inflammation,
      neoangiogenesis, and cancer, MIF and its signaling components are considered
      suitable targets for therapeutic intervention in several fields of medicine. In
      neurodegenerative and neurooncological diseases, MIF is a highly relevant, but
      still a hardly investigated mediator. MIF operates via intracellular protein
      protein interaction as well as in CD74/CXCR2/CXCR4 receptor-mediated pathways to
      regulate essential cellular systems such as redox balance, HIF-1, and p53
      mediated senescence and apoptosis as well as multiple signaling pathways. Acting
      as an endogenous glucocorticoid antagonist, MIF thus represents a relevant
      resistance gene in brain tumor therapies. Alongside this dual action, a
      functional homolog-annotated D-dopachrome tautomerase/MIF-2 has been uncovered
      utilizing the same cell surface receptor signaling cascade as MIF. Here we review
      MIF actions with respect to redox regulation in apoptosis and in tumor growth as
      well as its extracellular function with a focus on its potential role in brain
      diseases. We consider the possibility of MIF targeting in neurodegenerative
      processes and brain tumors by novel MIF-neutralizing approaches.

PMID- 22973317
TI  - Cardiac Epithelioid PEComa: Report of Two Cases and Review of the Literature.
AB  - Cardiac PEComa is very rare. We reported two cases of epithelioid PEComas, one in
      an adult and one in a 2-year-old child. Both tumors were composed of sheets of
      epithelioid cells with coagulation necrosis. In addition, the adult case showed
      marked nuclear atypia and high mitotic activity with atypical mitosis and the
      pediatric case showed unusual clear cell features. Immunohistochemically, both
      tumors were positive for HMB-45 and SMA and negative for S100 and cytokeratin.
      Electron microscopy was performed in the pediatric case and showed
      premelanosomes. The adult patient developed extensive metastasis indicating
      malignant behavior. Prior to the two cases, only 5 other cases of cardiac PEComa
      were reported and the literatures are reviewed.

PMID- 22973318
TI  - Omega-3 fatty acids, insulin resistance and type 2 diabetes.

PMID- 22973319
TI  - Prognostic factors for the survival of patients with esophageal cancer in
      Northern Iran.
AB  - BACKGROUND: Esophageal cancer is the 8(th) most common cancer and the 6(th)
      leading cause of cancer-related death, worldwide. In Iran, the high incidence
      rates of this type of cancer have been reported from the Caspian Sea region. This
      study aimed at assessing the factors affecting survival of patients with
      esophageal cancer in neighbor provinces around Caspian Sea using parametric and
      semi-parametric models with univariate gamma frailty model. METHODS: In this
      study, we performed a prospective review of 359 patients presenting with
      esophageal cancer from 1990 to 1991. The data were obtained using the Cancer
      Registry information existed in Babol research center in Iran. Study participants
      were followed-up until 2006 for a period of 15 years. Hazard ratio was used to
      interpret the risk of death. The Akaike Information Criterion (AIC) was
      considered as a criterion to select the best model(s). RESULTS: Of the 359
      patients, 225 (62.7%) were male with a mean age of 60.0 years and 134 (37.3%)
      were female with a mean age of 55.3 at the time of diagnosis. 1- , 3- and 5-year
      survival rates after diagnosis were 23%, 15% and 13% , respectively. Comparison
      between Cox and parametric models of AIC showed that the overall fitting was
      improved under parametric models. Among parametric models, the log-logistic model
      with gamma frailty provided better performance than other models. Using this
      model, we found that gender (p=0.012) and family history of cancer (p= 0.003)
      were significant predictors. CONCLUSIONS: Since the proportionality assumption of
      the Cox model was not held (p = 0.01), the Cox regression model was not an
      appropriate choice for analyzing our data. According to our findings, log
      logistic model with gamma frailty could be considered as a useful statistical
      model in survival analysis of patients with esophageal cancer rather than Cox and
      log-normal models.

PMID- 22973320
TI  - Relation of resistin levels with C-reactve protein, homocysteine and uric acid in
      smokers and non-smokers.
AB  - BACKGROUND: The association between C-reactive protein, homocysteine, uric acid
      levels and cardiovascular risk have been debated for decades. Resistin is a newly
      discovered adipocyte derived cytokine. Smoking besides its effect on
      atherosclerosis, is shown to alter adipocytokine levels. Bearing in mind, these
      complex relationship of resistin with smoking, C-reactive protein, homocysteine
      and uric acid, we planned to investigate the association of resistin and these
      cardiovascular risk factors in smoker and non-smoker subjects. METHODS: We
      conducted a cross-sectional randomized study including 52 smoking and 33 non
      smoking men. After making comparisons of C-reactive protein, homocysteine, uric
      acid and resistin between the two groups, we classified the subjects according to
      their insulin resistance and body mass and made again the comparisons.. RESULTS:
      Resistin levels were higher in smokers than in non-smokers (p<0.001) and also in
      insulin resistant than in non-insulin resistant smokers (p<0.05). Resistin levels
      were indifferent in non-smokers as insulin resistance was concerned and in smoker
      or non-smokers as body mass index was concerned. As all subjects were grouped
      based on homeostasis model assesment index and body mass index, neither C
      reactive protein nor homocysteine and uric acid levels differred. CONCLUSIONS: We
      found that smoking may have influence on resistin levels and in smokers, insulin
      resistance is related to resistin levels, but in smoker and non-smokers body mass
      may not have any association with resistin. Resistin also may not have a role in
      C-reactive protein, homocysteine and uric acid levels both in smokers and non
      smokers.

PMID- 22973321
TI  - Can serum procalcitonin and C-reactive protein as nosocomial infection markers in
      hospitalized patients without localizing signs?
AB  - BACKGROUND: Early diagnosis of infection with the use of valuable markers leads
      to decreased mortality and morbidity. The aim of this study was to evaluate the
      value of procalcitonin (PCT) and C-reactive protein (CRP) for detecting
      nosocomial infection in hospitalized patients without localizing signs. METHODS:
      We conducted a prospective observational study on 150 hospitalized patients with
      fever > 38 degrees C emerging 48-72 hours after their admission at Alzahra
      Hospital, Isfahan, Iran. The subjects did not have any localizing sign of
      infection. PCT and CRP values were determined using rapid tests and were compared
      with results of blood culture as the standard test. The sensitivity, specificity,
      positive and negative predictive values (PV) and likelihood ratios (LRs) were
      calculated for both PCT and CRP. Receiver operating characteristic (ROC) curves
      were also used to evaluate the diagnostic value of the PCT and CRP for detecting
      nosocomial infections. Finally, the areas under the resulting curves were
      compared. RESULTS: PCT had a sensitivity of 57.1%, a specificity of 89.1%, a
      positive PV of 46.2%, and a negative PV of 92.7% while the corresponding
      percentages for CRP test were 76.2%, 48%, 19.3%, and 92.5%. PCT marker also had a
      higher positive LR and lower negative LR than did CRP marker. The observed areas
      under the ROC curves were 0.73 for CRP (95% CI, 0.63-0.82; p = 0.023) and 0.80
      for PCT (95% CI, 0.68-0.91; p = 0.001). The optimal cut-off values (best
      diagnostic accuracy) were 39 mg/L for CRP and 7.5 ng/mL for PCT. CONCLUSIONS:
      Determination of PCT and CRP is a valuable tool for identifying nosocomial
      infections. PCT showed better specificity, negative and positive PV. However CRP
      showed significantly better sensitivity compared with PCT. Therefore, these tests
      should be considered as part of initial work-up for patients with unknown source
      of infection.

PMID- 22973322
TI  - Validity and reproducibility of a food frequency questionnaire for assessment of
      fruit and vegetable intake in Iranian adults(*).
AB  - BACKGROUND: This study's aim was to design and validate a semi-quantitative food
      frequency questionnaire (FFQ) for assessment of fruits and vegetables (FV)
      consumption in adults of Isfahan by comparing the FFQ with dietary reference
      method and blood plasma levels of beta-carotene, vitamin C, and retinol. METHODS:
      This validation study was performed on 123 healthy adults of Isfahan. FV intake
      was assessed using a 110-item FFQ. Data collection was performed during two
      different time periods to control for seasonal effects, fall/winter (cold season)
      and spring/summer (warm season). In each phase a FFQ and 1 day recall, and 2 days
      of food records as the dietary reference method were completed and plasma vitamin
      C, beta-carotene and retinol were measured. Data was analyzed by Pearson or
      Spearman and intraclass correlations. RESULTS: Serum Lipids, sex, age, body mass
      index (BMI) and educational level adjusted Pearson correlation coefficient of FV
      with plasma vitamin C, beta-carotene and retinol were 0.55, 0.47 and 0.28 in the
      cold season (p < 0.05) and 0.52, 0.45 and 0.35 in the warm season (p < 0.001),
      respectively. Energy and fat intake, sex, age, BMI and educational level adjusted
      Pearson correlation coefficient for FV with dietary reference method in the cold
      and warm seasons were 0.62 and 0.60, respectively (p < 0.001). Intraclass
      correlation for reproducibility of FFQ in FV was 0.65 (p<0.001). CONCLUSIONS: The
      designed FFQ had a good criterion validity and reproducibility for assessment of
      FV intake. Thus, it can serve as a valid tool in epidemiological studies to
      assess fruit and vegetable intake.

PMID- 22973323
TI  - Acute phase reactant dynamics and incidence of microvascular dysfunctions in type
      2 diabetes mellitus.
AB  - BACKGROUND: Acute Phase Reactants (APRs) have a wide range of activities that
      contribute to host defense. The aim of this report was to evaluate the dynamics
      and magnitude of these proteins in various microvascular complications in
      diabetes mellitus (DM). We also sought to assess the predictive values of APRs
      and other clinical variables for microvascular complications in DM. METHODS: This
      was a case control study carried out in 200 Nigerian subjects with type 2 DM and
      100 sex and age matched healthy controls. The studied APRs included C-reactive
      protein, beta 2 microglobulin, fibrinogen and lipoprotein (a). RESULTS: The mean
      values of the APRs were significantly higher in type 2 DM compared with the
      controls and were observed in higher concentrations in those with microvascular
      complications, except beta 2 microglobulin. Presence of microvascular
      complications was observed in those with dilated fundus examination
      (retinopathy), symptom score of 3.0 (neuropathy), urea and creatinine levels
      above 50mg% and 1.5mg%, respectively, with significant proteinuria (nephropathy).
      Significant increase in mean +/- SEM values of lipoprotein (a) was observed in
      diabetic retinopathy in comparison with those without complications (25.76 +/-
      1.13 mg/dl vs. 22.37 +/- 0.73 mg/dl, p = 0.005). Elevated C-reactive protein was
      observed in diabetic neuropathy in comparison with those without complications
      (11.43 +/- 2.33 u/ml vs. 8.30 +/- 1.15 u/ml, p = 0.048). Increased beta 2
      microglobulin levels were observed in patients with diabetic foot ulcers in
      comparison with those without complications (3.04 +/- 0.51 mg/dl vs. 2.54 +/-
      0.14 mg/dl, p = 0.049). Circulating levels of Lipoprotein (a) predicted
      retinopathy in DM with both good and poor long-term glycemic control while
      duration of DM predicted the occurrence of foot ulcers.. CONCLUSIONS: Increased
      level of APRs was associated with a number of microvascular complications and may
      play a role in the pathogenesis.

PMID- 22973324
TI  - Effects of hyperbaric oxygenation on survival time of aluminum phosphide
      intoxicated rats.
AB  - BACKGROUND: Aluminium phosphide (AlP) is used as a fumigant. It produces
      phosphine gas which is a mitochondrial poison. Although this poisoning has been
      repeatedly reported in literature with a high mortality rate, there is no known
      antidote for AlP intoxication. In the present study, we studied the effects of
      hyperbaric oxygenation (HBO) on the survival time of AlP intoxicated rats.
      METHODS: Intoxicated rats with AlP (11.5 mg/kg, oral gavage) were placed in
      hyperbaric oxygenation with different concentrations of compressed air and
      oxygen. RESULTS: All the animals exposed to AlP died within 5 days. The mean
      survival times of rats exposed to AlP without any intervention, treated with
      hyperbaric condition by compressed air, and treated with hyperbaric condition by
      pure O2 were 91 +/- 1, 262 +/- 8, and 276 +/- 6 minutes, respectively. In
      analysis of survival times, there was a significant difference between Group 2
      which received AlP and the groups which underwent intervention (Groups 2 and 3, p
      < 0.001; Groups 2 and 4, p < 0.001). CONCLUSIONS: Hyperbaric oxygenation may
      probably improve the survival time of the intoxicated rats with aluminium
      phosphide, but it may not decrease the mortality rate.

PMID- 22973325
TI  - Measurement of facial movements with Photoshop software during treatment of
      facial nerve palsy.
AB  - BACKGROUND: Evaluating the function of facial nerve is essential in order to
      determine the influences of various treatment methods. The aim of this study was
      to evaluate and assess the agreement of Photoshop scaling system versus the
      facial grading system (FGS). METHODS: In this semi-experimental study, thirty
      subjects with facial nerve paralysis were recruited. The evaluation of all
      patients before and after the treatment was performed by FGS and Photoshop
      measurements. RESULTS: The mean values of FGS before and after the treatment were
      35 +/- 25 and 67 +/- 24, respectively (p < 0.001). In Photoshop assessment, mean
      changes of face expressions in the impaired side relative to the normal side in
      rest position and three main movements of the face were 3.4 +/- 0.55 and 4.04 +/-
      0.49 millimeter before and after the treatment, respectively (p < 0.001).
      Spearman's correlation coefficient between different values in the two methods
      was 0.66 (p < 0.001). CONCLUSIONS: Evaluating the facial nerve palsy using
      Photoshop was more objective than using FGS. Therefore, it may be recommended to
      use this method instead.

PMID- 22973326
TI  - Using skew-symmetric mixed models for investigating the effect of different
      diabetic macular edema treatments by analyzing central macular thickness and
      visual acuity responses.
AB  - BACKGROUND: Diabetic Macular Edema (DME) is one of the major causes of visual
      loss and increase in central macular thickness (CMT). The aim of this study was
      to determine the efficacy of a single intravitreal injection of bevacizumab (IVB)
      alone or in combination with intravitreal triamcinolone acetonide (IVB/IVT)
      versus macular laser photocoagulation (MPC) as primary treatment for DME when
      confounders were considered. METHODS: Skew-symmetric bivariate mixed modeling
      according to best corrected visual acuity (BCVA) and CMT was done on the data of
      103 diabetic patients from ophthalmic research center of Labbafinejad medical
      center (Tehran, Iran) to determine the best DME treatment by adjusting the effect
      of confounders. RESULTS: Although there was no significant difference between
      IVB/IVT (p > 0.05), these two treatments increased BCVA and decreased CMT better
      than MPC (p < 0.05). The following three groups showed better treatment
      responses: 1) women, 2) patients with more diabetes duration, 3) patients whose
      CMT were higher and VA were lower at the beginning of the clinical trial.
      CONCLUSIONS: Using skew-symmetric mixed effect model as updated statistical
      method in presence of asymmetric or outlier data, we received different results
      compared to the same investigation on this study by analyzing BCVA and CMT
      simultaneously. This research demonstrated the effect of IVB alone or in
      combination with intravitreal IVB/IVT on visual power and decreasing CMT during
      follow up.

PMID- 22973327
TI  - Inter-rater reliability of modified Alberta Stroke program early computerized
      tomography score in patients with brain infarction.
AB  - BACKGROUND: The Alberta Stroke Program Early Computerized Tomography Score
      (ASPECTS) was used to detect significant early ischemic changes on brain CT of
      acute stroke patients. We designed the modified ASPECTS and compared it to the
      above system based on the inter-rater reliability. METHODS: A cross-sectional
      validation study was conducted based on the inter-rater reliability. The CT
      images were chosen from the stroke data bank of Ghaem hospital, Mashhad in 2010.
      The inclusion criteria were the presence of middle cerebral artery territory
      infarction and performance of CT within 6 hours after stroke onset. Axial CT
      scans were performed on a third-generation CT scanner (Siemens, ARTX, Germany).
      Section thickness above posterior fossa was 10 mm (130 kV, 150 mAs). Films were
      made at window level of 35 HU. The brain CTs were scored by four independent
      radiologists based on the ASPECTS and modified ASPECTS. The readers were blind to
      clinical information except symptom side. Cochrane Q and Kappa tests served for
      statistical analysis. RESULTS: 24 CT scans were available and of sufficient
      quality. Difference in distribution of dichotomized <=7 and >7 ASPECT scores
      between four raters was significant (Q=13.071, df=3, p=0.04). Distribution of
      dichotomized <6 and >=6 scores based on modified ASPECT system between 4 raters
      was not significantly different (Q=6.349, df=3, p=0.096). CONCLUSIONS: Modified
      ASPECT method is more reliable than ASPECTS in detecting major early ischemic
      changes in stroke patients candidated to tPA thrombolysis.

PMID- 22973328
TI  - Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with
      hemorrhagic shock induced by controlled bleeding.
AB  - BACKGROUND: The most common cause of shock in the surgical or trauma patient is
      hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of
      treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood
      transfusion, such as risk of transmission of infectious diseases, and access and
      maintenance limitations, treatment of shock with autologous blood seems to be a
      decent solution. Autologous blood accumulated in body cavities in traumatic
      bleeding (such hemothorax), and bloodshed in operation field during open heart or
      vascular surgeries, and similar situations, can be utilized again. In this study,
      autotransfusion effects compared with crystalloid fluid in the treatment of
      hemorrhagic shock was investigated. METHODS: After induction of hemorrhagic shock
      in dogs by Wiggers type controlled bleeding, treating them in a group with
      autologous blood and another group with Ringer lactate were performed, and the
      results of treatment were studied. RESULTS: There was no mortality in both
      treatment approaches. Immediately after treatment, crystalloid positive effects
      such as renormalized vital signs and appropriate consciousness were more
      noticeable than autotransfusion, while twenty-four hours after, the desired
      effects of autologous blood were more pronounced like decreased metabolic
      acidosis and improvement of diuresis. CONCLUSIONS: Crystalloid during the first
      hours after treatment of hemorrhagic shock may be better than autologous blood as
      preferred treatment, while autotransfusion showed its benefits some hours after.
      This finding can be used to develop better strategies for treatment of
      hemorrhagic shock.

PMID- 22973329
TI  - Comparison of prophylactic use of meperidine and two low doses of ketamine for
      prevention of post-anesthetic shivering: A randomized double-blind placebo
      controlled trial.
AB  - BACKGROUND: Postanesthetic shivering is one of the most common complications of
      anesthesia. We compared the efficacy of meperidine and two low doses of ketamine
      with placebo to prevent postanesthetic shivering after general anesthesia.
      METHODS: This was a prospective, randomized double-blind placebo controlled
      clinical trial involving 120 ASA I-II patients aging 20-50 years, undergoing
      endoscopic sinus surgery with general anesthesia. Patients were randomly
      allocated to receive meperidine 0.4 mg/kg (Group M, n = 30), ketamine 0.3 mg/kg
      (Group K(1), n = 30), ketamine 0.5 mg/kg (Group K(2), n = 30), or normal saline
      (Group N, n = 30) 20 minutes before completion of the surgery. Tympanic
      temperature, blood pressure, and heart rate were measured before and immediately
      after induction of anesthesia, 30 minutes after induction, and before
      administration of the study drugs. The drugs were prepared and diluted to a
      volume of 2 ml and presented as coded syringes. An investigator, blinded to the
      groups, graded postanesthetic shivering using a four-point scale. Statistical
      analyses were performed using Statistical Package for Social Sciences (SPSS)
      Windows version 16. A p-value < 0.05 was considered statistically significant.
      RESULTS: Patient characteristics of the four groups were similar. The number of
      patients with observed shivering in groups was 0, 3, 1, and 9 in Groups M, K(1),
      K(2) and N, respectively. The difference between groups M, K(1), and K(2) with
      Group N was statistically significant. However, differences between groups M and
      K(1), M and K(2), and K(1) and K(2) were not significant. The number of patients
      with a shivering score of 2 or 3 was higher in Group N compared with other
      groups. CONCLUSIONS: Prophylactic use of low doses of intravenous ketamine (0.3
      or 0.5 mg/kg) was found to be effective to prevent postanesthetic shivering.
      However, administration of 0.3 mg/kg ketamine lowered the rate of hallucination
      as compared with 0.5 mg/kg.

PMID- 22973330
TI  - Supplement consumption in body builder athletes.
AB  - BACKGROUND: Widespread use of supplements is observed among world athletes in
      different fields. The aim of this study was to estimate the prevalence and
      determinants of using supplements among body builder athletes. METHODS: This
      cross-sectional study was conducted on 250 men and 250 women from 30 different
      bodybuilding clubs. Participants were asked to complete a self-administered
      standardized anonymous check-list. RESULTS: Forty nine percent of the respondents
      declared supplement use. Men were more likely to take supplements than women
      (86.8% vs. 11.2%, p = 0.001). Reasons for using supplements were reported to be
      for health (45%), enhancing the immune system (40%) and improving athletic
      performance (25%). Most athletes (72%) had access to a nutritionist but underused
      this resource. Coaches (65%) had the greatest influence on supplementation
      practices followed by nutritionists (30%) and doctors (25%) after them.
      CONCLUSIONS: The prevalence of supplement use among bodybuilders was high. Sex,
      health-related issues and sport experts were determinant factors of supplement
      use.

PMID- 22973331
TI  - Effects of Dextromethorphan on reducing methadone dosage in opium addicts
      undergoing methadone maintenance therapy: A double blind randomized clinical
      trial.
AB  - BACKGROUND: Dextromethorphan (DM) is an N-methyl-D-aspartate (NMDA) receptor
      antagonist that may be useful during opiate addiction process, especially in
      reducing methadone consumption in methadone maintenance therapy (MMT). The goal
      of the current study was to evaluate the effects of oral administration of DM on
      reducing methadone dose in MMT used to treat illicit opioid drug abuse. METHODS:
      A double-blinded randomized clinical trial was designed. Seventy two opiate
      abusers undergoing MMT were randomly divided into two groups. Participants in the
      intervention group were medicated by DM while those in the control group received
      placebo. After a 6-week follow-up, methadone consumption dosage, quality of life
      (QOL) and withdrawal symptoms were assessed and compared between the two groups
      by repeated measure ANOVA statistical test. RESULTS: The mean of methadone
      consumption in the DM and control groups were 62.7 mg/day (52.7-72.7) and 70.4
      mg/day (60.4-80.4), respectively. No statistically significant difference was
      found between the two groups among the four evaluations made (F = 1.192, P =
      0.279). There were not any significant differences in withdrawal symptoms between
      the two groups (P > 0.05). Total mean scores of QOL in the intervention and
      control groups were 84.8 (78.7-90.8) and 77.8 (71.8-83.7) (P > 0.05),
      respectively. CONCLUSIONS: Although DM might be useful for opioid dependence
      treatment, results of the current study did not reveal any statistically
      significant differences. Therefore, further studies exploring this possibility
      are needed.

PMID- 22973332
TI  - Can repeated exposure to morphine change the spinal analgesic effects of
      lidocaine in rats?
AB  - BACKGROUND: Chronic opium exposure leads to altered response to opioid compounds.
      The aim of this study was to assess the behavioral effects of opium tolerance on
      the analgesic effects of intrathecal lidocaine in rats. METHODS: Twenty-four
      adult male Sprague Dawley rats with intrathecal (IT) catheters were divided into
      3 groups of 8. The first group was morphine tolerant and received IT lidocaine
      (ML). Rats in the second group were not morphine tolerant and received IT
      lidocaine (L), while the third group consisted of not morphine tolerant rats that
      received IT placebo. Tail flick test was done and maximal possible
      antinociceptive effects (MPAE) were compared using analysis of variance (ANOVA).
      RESULTS: While percent of MPAE significantly increased in the L group, it had a
      significant reduction in the ML group (P < 0.001). CONCLUSIONS: After intrathecal
      lidocaine administration, a hyperalgesic response was seen in morphine tolerant
      rats and an analgesic response was seen in the lidocaine group.

PMID- 22973333
TI  - Seroprevalence of Brucellosis among high risk individuals in Guilan, Iran.
AB  - BACKGROUND: Brucellosis is a major public health problem in developing countries
      and has remained endemic in Iran. The aim of this study was to investigate the
      Seroprevalence of Brucellosis among high risk individuals in Guilan, Iran.
      METHODS: In a cross-sectional study, 478 blood samples from people living in
      rural areas (n = 292) and 186 slaughterhouse workers were screened by slide
      agglutination and microplate agglutination tests. Seropositive specimens were
      analyzed with Elisa for IgG and IgM antibody. RESULTS: Seroprevalence of
      brucellosis among slaughterhouse workers and the people living in rural areas
      were 9.8% (n = 18) and 5.5% (n = 16), respectively (p = 0.04). A significant
      association was observed between the seropositivity and type of abattoir (p =
      0.04) and contact with animals (p = 0.02) among slaughterhouse workers as well as
      consumption of unpasteurized milk products (p = 0.02) in people living in rural
      areas. IgG antibodies titer was higher than IgM in seropositive cases of the
      slaughterhouse workers and the people living in rural areas. CONCLUSIONS:
      Seroprevalence of brucellosis in slaughterhouse workers was higher than people
      living in rural areas. Consumption of raw products and direct contact with
      domestic animals were found to be significant risk factor for brucellosis. High
      titer of IgG antibody among the two study groups indicated that most seropositive
      subjects were in chronic phase of brucellosis.

PMID- 22973334
TI  - Familiarity of medical residents at Kerman Medical University with evidence based
      medicine databases.
AB  - BACKGROUND: Using Evidence Based Medicine (EBM) in clinical practice is an
      important strategy for improving and updating medical services. Therefore, EBM
      has recently attracted a lot of attention in many medical schools around the
      world. In this study we tried to evaluate the familiarity of clinical residents
      who are one of the main clinical decision makers in public hospitals and also the
      next generation of specialists with EBM and EBM databases. METHODS: This was a
      cross-sectional study in 2010 in which clinical residents of Kerman Medical
      University (KMU) participated. Residents were asked about the four main EBM
      databases. The data was collected by a self-administered questionnaire. RESULTS:
      The data showed that from the respondents only 26.6% knew about EBM and only
      28.7% of the respondents were familiar with "Up to Date", 22.3% were familiar
      with "Ovid EBM Reviews", 6.4% were familiar with "Cochrane" and 5.3% were
      familiar with "BMJ Clinical Evidence". The frequencies of those that actually
      used the databases for clinical decision making and could answer the search
      questions were even less. CONCLUSIONS: The results showed most of the residents
      lack sufficient knowledge about EBM and its databases. The reason is probably the
      inexistence of a systematic and comprehensive curriculum for EBM education during
      their residency program or undergraduate program. Thus, due to the importance of
      learning EBM in this group, there is a necessity to plan a comprehensive and
      proper education schedule for EBM and EBM database use at the beginning or
      further stages of residency.

PMID- 22973335
TI  - High level increase in liver enzymes and severe thrombocytopenia in a male case
      of anorexia nervosa(*).
AB  - BACKGROUND: Anorexia nervosa (AN) is a difficult-to-treat psychosomatic disease.
      Very few cases of acute liver failure associated with AN have been described. We
      describe one patient who was affected by AN and presented high level increase of
      serum liver enzymes, along with sever thrombocytopenia. Then, we discuss the
      possible etiopathogenic factors. METHODS: A 14-year-old boy with AN was admitted
      in the pediatric psychiatric emergency department of Alzahra Hospital with
      impaired electrolyte levels, bradycardia, hypotension, liver dysfunction, and
      thrombocytopenia. RESULTS: A ten-time increase in liver enzymes and
      thrombocytopenia were observed on admission. After two months of treatment, the
      levels were within the normal range. CONCLUSIONS: Improvement of initial clinical
      symptoms and recovery of liver enzymes and thrombocytopenia after the treatment
      suggested that liver dysfunction and thrombocytopenia may be observed in AN
      patients and should be taken care of by physicians.

PMID- 22973336
TI  - Pelvic lymphoma: An unusual presentation.
AB  - Pelvic lymphoma is not a common condition and aggressive recurrence of chronic
      lymphocytic leukemia (CLL) as a cause is rarely reported. We report a case of
      lymphoma of left adnexa in a postmenopausal woman, with a three week history of
      abdominal and left flank pain. Past medical history was consistent with diagnosis
      of CLL. She had received chemotherapy. Due to abdominal and flank pain and
      abdominopelvic mass, exploratory laparotomy was done with the impression of
      ovarian malignancy. A large uterus with adnexal mass and a large tumoral bladder
      was seen. Biopsy was done from adnexal mass which was compatible with lymphoma.
      The abdomen was closed and the patient was referred for chemotherapy. Lymphoma
      usually does not involve the pelvic organs. After laparotomy, her condition
      deteriorated and she expired.

PMID- 22973337
TI  - Treadmill running improves spatial learning and memory in the rats with
      intracerebroventricular injection of streptozotocin.

PMID- 22973338
TI  - The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin
      induced nephrotoxicity: Gender related differences in rat model.
AB  - BACKGROUND: Cisplatin (CP) as a potential drug for solid tumors produces
      nephrotoxicity and disturbs endothelial function. CP induced nephrotoxicity may
      be gender related. Nitric oxide plays a pivotal role in endothelial function and
      L-arginine as endogenous NO donor promotes endothelial function. The role of L
      arginine in CP induced nephrotoxicity model and its gender related was
      investigated in this study. METHODS: Thirty three Wistar rats were randomly
      assigned to four groups. The groups 1 (male, n = 6) and 2 (female, n = 11)
      received a single dose of L-arginine (300 mg/kg, ip), and the day after, they
      received a single dose of CP (7 mg/kg). The group 3 (male, n = 9) and 4 (female,
      n = 7) were assigned to the same regimen except for saline instead of L-arginine.
      All animals were sacrificed one week after CP administration. The levels of blood
      urea nitrogen (BUN), creatinine and nitrite were measured. The kidneys were also
      removed for pathological investigations. RESULTS: Five animals died. All CP
      treated animals lost weight. The normalized weigh loss was significantly
      different between male and female in CP+L-arginine treated animals (p < 0.05).
      BUN and creatinine were increased significantly in male treated with CP and in
      female treated with CP+L-arginine (p < 0.05). L-arginine reduced BUN in male (not
      in female) when compared with control groups (p < 0.05). The level of nitrite was
      increased significantly in L-arginine treated animals. Kidney tissue damage score
      and normalized kidney weight were greater in females treated with CP+ L-arginine
      than female received CP alone (p < 0.05). CONCLUSIONS: L-arginine may protect
      against CP induced nephrotoxicity in male, but it promotes the induced damage in
      female. The exact mechanism need to be defined.

PMID- 22973339
TI  - Relationship between echocardiographic findings and laboratory serum biomarkers
      in patients with and without low cardiac output.
AB  - BACKGROUND: Cardiac dysfunction is seen in many patients and could be evaluated
      with echocardiography and serum biomarkers. The aim of this study was evaluation
      of the relationship between echocardiographic findings and laboratory serum
      biomarkers in children with and without low cardiac output. METHODS: Thirty
      patients older than 1 month with and without low cardiac output were enrolled in
      this study. It composed of 13 patients with dilated cardiomyopathy (DCM), 7 with
      end stage renal disease (ESRD) and 10 who had a Fontan operation.
      Echocardiography was performed with emphasis on shortening fraction (SF) and
      ejection fraction (EF). Blood samples were collected for measurement of atrial
      natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP) and
      alkaline phosphatase (Alk-P). Both echocardiographic findings and laboratory data
      were compared with control levels in twenty-seven normal children. Pearson
      correlation and regression analysis were conducted to evaluate the aforementioned
      associations. RESULTS: The mean of ANP and hs-CRP in the case group was
      statistically higher than control group (p < 0.001). The mean of ANP and hs-CRP
      were different in all groups (p < 0.001). There was a reverse linear regression
      between the SF and ANP in the case group (r = -0.594, p < 0.001). CONCLUSIONS:
      Determination of the plasma ANP and hs-CRP level may be helpful for decisions
      related to early diagnosis of patient with low cardiac output.

PMID- 22973340
TI  - Tumor necrosis factor alpha and high sensitivity C-reactive protein in diagnosis
      of exudative pleural effusion.
AB  - BACKGROUND: Differentiation between exudative and transudative pleural effusions
      is the initial step in assessment of pleural effusion. The aim of this study was
      to determine whether high sensitivity C-reactive protein (hsCRP) and tumor
      necrosis factor alpha (TNFalpha) are diagnostic utilities for exudative pleural
      effusion. METHODS: This experimental study assessed 79 patients with pleural
      effusion who underwent diagnostic evaluations at Imam Reza hospital, Mashhad,
      Iran in 2009-2010. The complete biochemical analysis of pleural fluid, pleural
      fluid culture, and pathological examination of pleural fluid and tissue were
      performed. Moreover, hsCRP and TNFalpha concentrations were measured in pleural
      fluid samples. The data was analyzed by student's t-test and Mann-Whitney test.
      RESULTS: According to Light's criteria, 50 patients (63.30%) had exudative
      effusions while 29 subjects (36.70%) had transudative effusion. The pleural fluid
      concentrations of hsCRP and TNFalpha were significantly higher in the exudative
      group than the transudative group (p < 0.05). At a cutoff value of 5 mg/L for
      hsCRP, the results showed 94% sensitivity and 96.6% specificity. Regarding
      TNFalpha, a cutoff value of 12.9 ng/dl represented 96% sensitivity and 93%
      specificity. CONCLUSIONS: HsCRP and TNFalpha levels may be considered as
      beneficial diagnostic factors for detecting exudative effusion in patients with
      pleural effusion.

PMID- 22973341
TI  - The effects of moderate-dose steroid therapy in sepsis: A placebo-controlled,
      randomized study.
AB  - BACKGROUND: Despite the new developments in sepsis treatment, mortality rate is
      still high. In this study, we aimed to investigate endocrinologic changes and the
      effects of moderate dosage steroid treatment in patients with sepsis. METHODS:
      Fifty-five patients were included in the study. Basal hormonal evaluation and
      adrenocorticotropin hormone (ACTH) stimulation test were performed within 24 h in
      all patients. Both groups received standard treatment for sepsis. However, one
      group (steroid group) was also given intravenous prednisolone (20 mg/day). All
      cause mortality was assessed during the first 28 days. RESULTS: Analysis of the
      findings revealed a 59.3% mortality rate in steroid group compared with a 53.6%
      mortality rate in placebo group (p = 0.787). Acute Physiology and Chronic Health
      Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, and
      peak cortisol and ACTH levels were significant factors related to mortality. The
      incidence of adrenal insufficiency (AI) was 10.9% and relative adrenal
      insufficiency (RAI) 36.4%. It was also found that steroid treatment did not have
      any effects on the mortality of patients with AI and RAI (p = 0.075 and p =
      0.999, respectively). CONCLUSIONS: Moderate-dose steroid therapy has no effect on
      mortality. Higher basal cortisol and peak cortisol levels were found more
      reliable mortality indicators compared to RAI. In addition, the study revealed
      that ACTH level was a significant indicator of mortality.

PMID- 22973342
TI  - Visual outcome of early and late pars plana vitrectomy in patients with dropped
      nucleus during phacoemulsification.
AB  - BACKGROUND: Dislocated lens fragments in the vitreous cavity can cause
      potentially serious complications. This retrospective study aimed to evaluate the
      visual outcome of patients who underwent pars plana vitrectomy (PPV) for
      posteriorly dislocated lens fragments after cataract phacoemulsification.
      METHODS: A retrospective study was conducted on all consecutive cases (60
      patients) with pars plana vitrectomy performed for retained lens fragment. In 30
      eyes (50%), PPV was performed within 1 week of cataract extraction and in 30 eyes
      (50 %), PPV was performed more than 1 week post cataract extraction from July
      2005 through August 2008. RESULTS: In the late vitrectomy group, 66.6% of eyes
      developed persistent uveitis, 53.3% of eyes showed elevated intra-ocular pressure
      (IOP) and 5 eyes retinal detachment. In early PPV group 16.6% developed uveitis
      and 20% showed elevated IOP and one eye retinal detachment. The final visual
      acuity was 20 +/- 50 in early PPV and 20 +/- 200 in late PPV group (mean +/- SD,
      p < 0.001). CONCLUSIONS: The early use of PPV to remove posterior dislocated lens
      fragments within the first week was shown to be advantageous. The inflammatory
      response was less pronounced, IOP rose less significant, the incidence of retinal
      detachment was lower and visual recovery was faster.

PMID- 22973343
TI  - The angular profile of the knee in Iranian children: A clinical evaluation.
AB  - BACKGROUND: Intercondylar (IC) and intermalleolar (IM) distance measurements are
      appropriate modalities for screening angular deformities but the values are not
      the same in all ethnics. This study was conducted to assess the mean values and
      normal limits of IC and IM distances in Iranian children. METHODS: A total of
      2268 children aged eight to eleven years were recruited in this research project.
      The IC and IM distances were measured and recorded according to a special
      procedure in standing and supine positions. RESULTS: The mean values of IC
      distance were 2.4 +/- 6.05 and 3.83 +/- 8.1 mm in supine and standing positions,
      respectively, while the corresponding IM distances were 5.63 +/- 10.74 and 7.51
      +/- 11.22 mm. There was no significant difference among the age groups. Moreover,
      the mean values of these parameters did not differ significantly between two
      genders. CONCLUSIONS: With respect to reported values, IC and IM measurements,
      especially when selected according to age, can be used for screening angular
      deformities of lower limbs.

PMID- 22973344
TI  - Frequency of Entamoeba histolytica and Entamoeba dispar prevalence among patients
      with gastrointestinal complaints in Chelgerd city, southwest of Iran(*).
AB  - BACKGROUND: Differentiation between Entamoeba histolytica and Entamoeba dispar is
      very important for both clinical therapy and epidemiological studies. Although
      these two species are morphologically identical, they have differences in
      genetic, chemical specifications and pathogenicity. This study was carried out to
      differentiate E. histolytica from E. dispar and also to find out frequency of the
      two species. METHODS: Fecal samples were collected three times from 655 patients
      with gastrointestinal complaints (47.3% male and 52.7% female), who were referred
      to the primary health care centers of Chelgerd, Chaharmahal and Bakhtiary
      province. Samples were examined microscopically with direct smear, formalin-ethyl
      acetate concentration and trichrom staining methods to distinguish E. histolytica
      from E. dispar complex and differentiate them from non-pathogenic intestinal
      amoeba. Genomic DNA was extracted from microscopy positive isolates and
      polymerase chain reaction (PCR) was carried out to different the two
      morphologically identical Entamoeba isolates. RESULTS: Among the 655 recruited
      patients, eleven subjects with E. histolytica / E. dispar isolates (1.7%) were
      identified by microscopy methods. Ten of the positive isolates (90.9%) were
      identified as E. histolytica by PCR and one isolate (9.09 %) was positive for E.
      dispar. CONCLUSIONS: This study revealed that E. histolytica was more prevalent
      than E. dispar in the studied area. This result was different from the previously
      reported data in other parts of Iran.

PMID- 22973345
TI  - Symptoms of anxiety and depression: A comparison among patients with different
      chronic conditions.
AB  - BACKGROUND: Although patients with chronic diseases are at high-risk for symptoms
      of anxiety and depression, few studies have compared patients with different
      chronic conditions in this regard. This study aimed to compare patients with
      different chronic medical conditions in terms of anxiety and depression symptoms
      after controlling for the effects of socio-demographic and clinical data.
      METHODS: This cross-sectional study enrolled 2234 adults, either healthy (n =
      362) or patients with chronic medical conditions (n = 1872). Participants were
      recruited from the outpatient clinic of Baqiyatallah Hospital, Tehran, Iran.
      Patients had one of the following five medical conditions: coronary artery
      disease (n = 675), renal transplantation (n = 383), chronic hemodialysis (n =
      68), rheumatoid conditions (rheumatoid arthritis, osteoarthritis, systemic lupus
      erythematosus and ankylosing spondylitis) (n = 666) and viral hepatitis (n = 80).
      Independent factors included socio-demographic data, pain disability, and somatic
      comorbidities (Ifudu index). Outcomes included symptoms of anxiety and depression
      through Hospital Anxiety and Depression Scale (HADS). Two multinomial regression
      models were used to determine the predictors of anxiety and depression symptoms.
      RESULTS: After controlling the effect of age, sex, educational level,
      comorbidities, disability and pain, rheumatoid arthritis and hepatitis were
      predictors of higher anxiety symptoms, while coronary artery disease and chronic
      hemodialysis were predictors of depression symptoms. CONCLUSIONS: Although all
      chronic conditions may require psychological consideration; be that as it may,
      different chronic diseases are dissimilar in terms of their mental health need.
      Anxiety for rheumatoid arthritis and hepatitis as well as depression for coronary
      artery disease and chronic hemodialysis is more important.

PMID- 22973346
TI  - The effect of mechanical lymph drainage accompanied with heat on lymphedema.
AB  - BACKGROUND: Thermotherapy has been indicated by some researchers as a treatment
      for lymphedema. A study comparing temperatures demonstrated that a temperature of
      40 degrees C significantly increased the transportation of lymph compared to
      other temperatures assessed. The aim of this study was to evaluate the possible
      benefits of mechanical lymph drainage accompanied with heat in the treatment of
      lymphedema of the lower limbs. METHODS: In a cross-over randomized study, the
      effect of heat on lymph drainage was evaluated in the treatment of leg
      lymphedema. The study, performed in the Godoy Clinic in Sao Jose do Rio Preto,
      Brazil, involved seven patients (two males and five females) with leg lymphedema.
      The patients' ages ranged from 18 to 79 years old with a mean of 48.5 years. The
      subjects underwent a total of 38 assessments including 19 evaluations of
      mechanical lymph drainage alone and 19 combined with thermotherapy. Heat was
      applied using an electric blanket which was wrapped around the legs of the
      patients. The volume of legs was evaluated by water plethysmography before and
      after treatment sessions. The paired t-test was used for statistical analysis
      with an alpha error of p = 0.05 being considered as acceptable. RESULTS: No
      statistically significant differences were evidenced between mechanical lymph
      drainage alone and lymph drainage combined with thermotherapy. CONCLUSIONS: There
      was no obvious synergic effect in the immediate post-treatment period when heat
      was combined with mechanical lymph drainage in the treatment of lymphedema.

PMID- 22973347
TI  - The knowledge and attitudes of a female at-risk population towards the prevention
      of AIDS and sexually transmitted infections in Tehran.
AB  - BACKGROUND: The female at-risk population represents a subgroup that is both a
      crucial determining factor in acquired immune deficiency syndrome (AIDS)
      transmission and a gap in the existing literature in Iran. The objective of this
      study was to evaluate the level of sex workers' knowledge towards to safe
      procedures of sexually transmitted infection and AIDS prevention as well as
      attitudes towards AIDS. METHODS: A sample of 256 female sex workers working in
      Tehran was obtained by a variety of methods. Appropriate questions for the
      assessment of knowledge and attitude were developed based on previous studies.
      RESULTS: The mean age of the subjects was 26.8 +/- 6.1 years (ranging from 16 to
      45). Methods of transmission were widely recognized, despite the exception that
      few realized oral (23.4%) and anal (44.9%) intercourse as methods of human
      immunodeficiency virus (HIV) transmission. Most subjects knew that AIDS currently
      has no cure (81.2%) and no vaccine (73.4%). Most also acknowledged that HIV is
      transmissible from people who do not know they are HIV positive (59.4%), proper
      condom use can reduce the possibility of infection (78.1%), and so can having a
      single sexual partner (68.8%). Of the participants, 43.4% knew that an HIV
      positive person can seem perfectly healthy. CONCLUSIONS: Knowledge towards
      sexually transmitted infections (STIs) and condom use is still inadequate,
      especially regarding risky behaviors such as anal sex, and attitudes are mainly
      negative. Identifying at-risk populations, HIV-positive sex workers, education
      and campaigns to change the attitudes towards AIDS should be regarded a high
      priority in Iran.

PMID- 22973348
TI  - Reduction of proteinuria by pioglitazone in patients with non-diabetic renal
      disease.
AB  - BACKGROUND: Increased proteinuria would lead to a larger risk for renal failure
      in the long term. Therefore, proteinuria requires immediate and thorough
      evaluation. This study was designed to evaluate the effects of pioglitazone on
      proteinuria in patients with non-diabetic renal disease. METHODS: In this self
      controlled clinical trial study, forty four non-diabetic patients aged 18 and
      more, who had renal disease and a stable proteinuria of over 0.5 g in 24 hour,
      were studied. All patients received 15 mg of daily pioglitazone for 4 months.
      Urine protein excretion was measured as a main end point prior to the study, at
      the end of the 2nd and 4th months of treatment, and 2 and 4 months after the
      cessation of the active drug. Other evaluated variables included systolic blood
      pressure, serum creatinine, urea, alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), fasting blood sugar (FBS), blood urea nitrogen (BUN) and
      glomerular filtration rate (GFR) levels. RESULTS: Proteinuria (mean +/- SEM)
      prior to the study, at the 2nd and 4th months of the treatment, and 2 and 4
      months after the cessation of pioglitazone were 1088.6 +/- 131.1, 699.9 +/-
      118.3, 433.9 +/- 68.7, 416.1 +/- 54.9 and 646.9 +/- 89.1, respectively (p <
      0.001). In addition, the reduction of 24-hour urine protein was statistically
      significant for both male and female patients (p < 0.001 for both). CONCLUSIONS:
      A reduction of proteinuria in patients with non-diabetic renal disease was
      observed during the 4-month treatment with pioglitazone which continued for 2
      months after the cessation of the treatment. However, 4 months after the
      cessation of the treatment, a little increase was detected in the level of
      proteinuria.

PMID- 22973349
TI  - Cognitive impairments in patients with intractable temporal lobe epilepsy.
AB  - BACKGROUND: Cognitive impairment associated with temporal lobe epilepsy (TLE) has
      been recognized in multiple studies. We designed this study to find a specific
      cognitive profile in patients with TLE who were candidates for epilepsy surgery.
      We also sought to find if neuropsychological assessment could differentiate left
      TLE, right TLE and normal subjects. METHODS: The sample of this study consisted
      of 29 patients with right TLE, 31 with left TLE, and 32 subjects without history
      of seizure as the control group. For all recruited patients and controls,
      demographic questionnaire, Wechsler Memory Scale-III (WMS-III) and Wechsler Adult
      Intelligence Scale-R (WAIS-R) were administered. Multivariate analysis of
      variance was carried out to reveal differences in memory and intelligence
      performance between the three groups. RESULTS: All of the mean scores of the WMS
      III indexes were significantly higher in the control group in comparison with the
      right or the left TLE groups (p < 0.001). There were not any significant
      differences between mean scores of WMS-III indexes of the right and the left. The
      WAIS-R also showed significantly better mean scores of full scale intelligence
      quotient (FSIQ) and performance intelligence quotient (PIQ) in the control groups
      than both of the right and left TLE patients (p < 0.001). Although the verbal
      intelligence quotient (VIQ) mean scores were significantly different between the
      left TLE and the control group (p = 0.037), there were not any significant
      differences between the right TLE patients and the control group. CONCLUSIONS:
      These findings indicated that WMS-III and WAIS-R can differentiate patients with
      refractory temporal lobe epilepsy from normal subjects. However, the obtained
      cognitive profile could not differentiate between the right and the left TLE.

PMID- 22973350
TI  - Ischemia detection by electrocardiogram in wavelet domain using entropy measure.
AB  - BACKGROUND: Ischemic heart disease is one of the common fatal diseases in
      advanced countries. Because signal perturbation in healthy people is less than
      signal perturbation in patients, entropy measure can be used as an appropriate
      feature for ischemia detection. METHODS: Four entropy-based methods comprising of
      using electrocardiogram (ECG) signal directly, wavelet sub-bands of ECG signals,
      extracted ST segments and reconstructed signal from time-frequency feature of ST
      segments in wavelet domain were investigated to distinguish between ECG signal of
      healthy individuals and patients. We used exercise treadmill test as a gold
      standard, with a sample of 40 patients who had ischemic signs based on initial
      diagnosis of medical practitioner. RESULTS: The suggested technique in wavelet
      domain resulted in the highest discrepancy between healthy individuals and
      patients in comparison to other methods. Specificity and sensitivity of this
      method were 95% and 94% respectively. CONCLUSIONS: The method based on wavelet
      sub-bands outperformed the others.

PMID- 22973351
TI  - The effects of carbohydrate-rich drink on perioperative discomfort, insulin
      response and arterial pressure in spinal aesthesia.
AB  - BACKGROUND: The aim of this study was to investigate the role of carbohydrate
      rich drink (CHO) on perioperative discomfort, hemodynamic changes, and insulin
      response in patients undergoing surgery with spinal anesthesia. METHODS: Forty
      four adult patients were assigned to one of the two groups of 22, namely
      preparation with CHO (CHO group) or fasting from midnight (control group). Ten
      different discomfort variables, blood glucose and insulin concentrations, and
      hemodynamic changes were recorded during the perioperative period. RESULTS:
      Preparation with CHO was effective in reducing hunger, thirst, malaise,
      unfitness, and, to some extent, anxiety (p < 0.05). Plasma glucose and insulin
      concentrations were increased in the CHO group (p < 0.05). Plasma glucose
      increased and insulin decreased in the control group (p < 0.05). In the control
      group, mean arterial pressure was lower compared to the CHO group (p < 0.05).
      CONCLUSIONS: Preparation with CHO before spinal anesthesia is advantageous due to
      reducing perioperative discomfort, improving insulin response and stabilizing
      mean arterial pressure.

PMID- 22973352
TI  - Prevention of etomidate-related myoclonus in anesthetic induction by pretreatment
      with magnesium.
AB  - BACKGROUND: Etomidate frequently leads to myoclonic jerks during anesthetic
      induction. This study aimed to detect if pretreatment with magnesium decreases
      myoclonus incidence. METHODS: A hundred ASA (the American Society of
      Anesthesiologists) I-II patients were included and randomized into 2 groups.
      Three minutes before etomidate induction of anesthesia (by 0.3 mg/kg intravenous
      etomidate), Group M received 2.48 mmol (60 mg) intravenous magnesium sulphate and
      Group P received equal volume of intravenous saline. Myoclonus was evaluated as
      "present/absent". RESULTS: The rate of myoclonus was significantly lower in Group
      M than in Group P (p < 0.01). Hemodynamic parameters revealed no significant
      difference between the two groups. CONCLUSIONS: Low dose magnesium pretreatment
      before etomidate induction of anesthesia significantly reduces unwanted myoclonic
      jerks and also protects the hemodynamic stability.

PMID- 22973353
TI  - Effect of shift work on patient-doctor relationship in emergency department.
AB  - BACKGROUND: This study aimed to find effect of shift work on patient-doctor
      relationship in Emergency Department. METHODS: In a prospective cross-sectional
      study, 352 patients (mean age of 44 +/- 17 years, 131 females and 221 males)
      referred to the emergency department of Rasoul-Akram hospital were enrolled in
      the study. The patient-doctor relationship questionnaire (PDRQ) was asked to be
      filled by patients. The questionnaires contained 9 items and the appropriateness
      of the statements was simplified to a scale of 1 (not at all) through 5
      (totally). RESULTS: Comparing three shift works, the highest PDRQ score was for
      morning (27.1 +/- 5.5) and the lowest value was for afternoon shift (23.8 +/-
      5.3). PDRQ score for night shift was 25.1 +/- 6.9 (p = 0.002). CONCLUSIONS: The
      results of this study encouraged that patients' satisfaction of relationship with
      doctors was the lowest in the afternoon and it may be better to implement some
      strategies to reduce residents' workloads and increase quality of works in the
      afternoon shifts.

PMID- 22973354
TI  - Combined portal, splenic and mesenteric venous thrombosis in inactive ulcerative
      colitis with heterozygous mutation in MTHFR gene: A rare case of thrombophilia.
AB  - Thrombophilia is a rare but potentially catastrophic phenomenon occurring in
      patients having tendency of thrombosis. It may lead to serious complications. The
      etiology of thrombophilia is thought to be multifactorial and related to both
      acquired and inherited factors. Inflammatory bowel disease is an acquired cause
      of thrombophilia. Thromboembolic events are seen during inflammatory bowel
      disease, especially during the active period of the disease. In inflammatory
      bowel disease, thrombus formation in portal, splenic and mesenteric veins are not
      common. Besides, the association of genetic disorders related to metabolism of
      homocysteine with inflammatory bowel disease has been evidenced, especially in
      Crohn disease and rarely in ulcerative colitis. We present a rare case of
      ulcerative colitis in association with combined portal, splenic and mesenteric
      vein thrombosis. The patient was recently diagnosed with the disease which was in
      the inactive period. Interestingly, our patient was also heterozygous for the
      mutation in methylenetetrahydrofolate reductase (MTHFR) gene.

PMID- 22973355
TI  - Visceral leishmaniasis in a patient with cutaneous lesions, negative Leishman
      Donovan bodies and immunological test: A case report.
AB  - We report a case of visceral leishmaniasis (VL) in a patient from Shush in Iran
      with cutaneous lesions, negative for Leishman-Donovan bodies, enlarged spleen
      filled by leishmania protozoa and negative immunological test. The patient was a
      26-year-old male, who attended hospital with fever and two deep purulent lesions
      on the distal part of his left leg. On physical examination, the patient had
      splenomegaly. Laboratory results were as follows: pancytopenia, positive C
      reactive protein (CRP), elevated erythrocyte sedimentation rate (ESR) and lactate
      dehydrogenase (LDH) levels .The necessary treatment was administrated to the
      patient. Biopsy of lesion for Leishman-Donovan body was negative. In addition,
      indirect fluorescent antibody (IFA) screening for leishmaniasis was negative.
      Diagnostic splenectomy was performed which pathological exploration showed a bulk
      of leishmania protozoa in patient's spleen. Twenty days later, this patient
      expired.

PMID- 22973356
TI  - Endoscopic resection of large colonic lipomas assisted by a prototype single-use
      endoloop device.
AB  - Colonic lipomas are benign adipose tumors that do not usually cause symptoms.
      Giant colonic lipoma (GCL) is an uncommon finding at endoscopy which may lead to
      iron deficiency anemia (IDA) with or without macroscopic ulceration. The choice
      of therapeutic procedure to treat symptomatic GCLs has been controversial. A case
      of GCL presented with occult bleeding and IDA is reported in this article. IDA
      resolved following the successful removal of the GCL by a combination of endoloop
      ligation and snare cautery technique.

PMID- 22973357
TI  - Comparison between the efficacy of Q-Switched 1064-nm Nd: YAG laser and Fraxel
      CO(2) laser on improvement of atrophic facial acne scars: A letter to editor.

PMID- 22973358
TI  - Polymorphism of Apo lipoprotein E gene and the risk of multiple sclerosis.
AB  - BACKGROUND: Apolipoprotein E (ApoE) gene encodes an important protein in
      reforming injuries of central nervous system (CNS). It is assumed that various
      ApoE alleles may be functionally different. The purpose of this study was to
      investigate the distribution of ApoE genotypes in multiple sclerosis (MS)
      patients in a small cohort of Iranians. METHODS: In this case-control study,
      blood samples of patients and healthy volunteers were collected (n = 40) from
      Neurology Clinic of Alzahra Medical Complex. The ApoE genotypes were determined
      using DNA extracted from the samples by polymerase chain reaction (PCR)
      techniques followed by digestion with HhaI restriction enzyme. The results were
      adjusted for age of MS onset, sex, expanded disability status scale (EDSS), and
      type of MS (primary or secondary progressive). Results were statistically
      analyzed using chi-square test. RESULTS: The ApoE3/E3 genotype was detected in
      the majority of MS patients and the control group. Frequency distribution of E4
      allele did not differ significantly between the two groups. There was no
      difference between ApoE allele and age of disease onset, sex, expanded disability
      status, or type of multiple sclerosis. CONCLUSIONS: We found no significant
      differences in genotype frequency between patients with multiple sclerosis and
      the control group. Despite the fact that small sample size was a limitation for
      our study, it seems that ApoE polymorphism may not be useful as a marker for
      screening patients with multiple sclerosis.

PMID- 22973359
TI  - The effects of sertraline on blood lipids, glucose, insulin and HBA1C levels: A
      prospective clinical trial on depressive patients.
AB  - BACKGROUND: In this study, we aimed to investigate the possible effects of
      sertraline on blood glucose and lipid levels as risk factors for cardiovascular
      disease in depressive patients. METHODS: Eight male and twelve female depressive
      patients, diagnosed according to DSM-IV criteria, were included in this study.
      The subjects aged 19-50 years, did not smoke, and had normal body mass index
      (BMI), homeostasis model assessment-estimated insulin resistance (HOMA-IR)
      values, blood pressure, blood glucose, insulin and lipid levels. Sertraline
      therapy (50 mg/day) was started. Patients with diabetes mellitus, heart disease,
      pregnancy, and those taking other drugs were excluded from the study. Blood
      glucose, insulin, high-density lipoprotein-cholesterol (HDL-C), low-density
      lipoprotein-cholesterol (LDL-C), and triglyceride values were measured in
      patients before, and at the 4(th), 8(th) and 12(th) weeks after treatment with
      sertraline. Moreover, HbA1C levels were measured at the beginning and at the end
      of the treatment (at 12(th) weeks). RESULTS: There were no significant
      differences in physical examination (blood pressure, BMI, body weight, height,
      waist circumference) and laboratory findings (glucose, HDL-C, LDL-C, HOMA-IR and
      HbA1C levels) at the 12(th) week after of treatment with sertraline compared to
      pretreatment values. However, insulin levels at the 4(th), 8(th) and 12(th) weeks
      significantly increased compared with pretreatment values. Likewise, triglyceride
      levels at the 8(th) and 12(th) weeks significantly increased compared with
      pretreatment values. CONCLUSIONS: Sertraline-treated patients have to be followed
      up for blood insulin and triglyceride levels. In addition, their treatment plan
      needs to be adjusted as necessary to prevent possible metabolic changes.

PMID- 22973360
TI  - Association of adiponectin and metabolic syndrome in women.
AB  - BACKGROUND: An inverse association between serum adiponectin level and metabolic
      syndrome was seen in few studies. The aim of this study was to assess the
      association between serum adiponectin levels and metabolic syndrome in a sample
      of Iranian women from Kerman. METHODS: In a cross-sectional study 946 subjects
      were studied to determine the prevalence of metabolic syndrome and in a case
      control study (170 subjects for each group) the association between serum
      adiponectin levels and metabolic syndrome were investigated. Metabolic syndrome
      was defined using International Diabetes Federation (IDF) criteria. Socio
      demographics factors and measures of waist circumference, blood pressure and
      lipid profiles were collected. Serum adiponectin level was measured by ELISA
      method. RESULTS: The prevalence of the metabolic syndrome was 36.7%. Mean of
      serum adiponectin level in individuals with metabolic syndrome was lower than
      individuals without it (10.5 +/- 4.1 and 13.45 +/- 5.6 MUg/ml, respectively, p <
      0.001). Low level of adiponectin was a good predictor for metabolic syndrome (a
      range of beta coefficients out of -2.03 to -2.85 according to five models).
      Systolic blood pressure, body mass index (BMI) and diastolic blood pressure were
      independent predictors of serum adiponectin (p values were 0.001, 0.009 and
      0.034, respectively). CONCLUSIONS: We found that adiponectin is negatively
      associated with metabolic syndrome. Systolic and diastolic blood pressure and BMI
      were identified as independent predictors.

PMID- 22973361
TI  - The effect of consuming oxidized oil supplemented with fiber on lipid profiles in
      rat model.
AB  - BACKGROUND: This study was conducted to evaluate the effects of consuming
      thermally oxidized oil supplemented with pectin on liver glutathione peroxidase
      activity, serum malondialdehyde and lipid profiles in male Sprague-Dawley rats.
      METHODS: Fifty growing male Sprague-Dawley rats were randomly divided into
      different groups. The diets differed only in their fat and pectin content. The
      diets had fresh sunflower oil or thermally oxidized sunflower oil. The diets were
      supplemented with pectin in the amount of 50 g/kg diet or not supplemented. Thus,
      there were four experimental groups: "fresh oil", "oxidized oil", "fresh oil +
      pectin", "oxidized oil + pectin". Study duration was 42 days. Non parametric,
      Kruskal-Wallis and Mann-Whitney tests were used to evaluate mean values of
      variables in groups. RESULTS: In oil consumption, peroxide, p- Anisidine,
      thiobarbituric acid, free fatty acid values and total polar compounds increased
      but iodine value was decreased. In the oxidized oil group compared to the fresh
      oil group, total cholesterol, high density lipoprotein cholesterol and
      malondialdehyde increased (p < 0.05). Serum malondialdehyde was decreased in the
      "oxidized oil + pectin" group compared to the oxidized oil alone (2.82 +/- 0.51
      vs. 3.61 +/- 0.72 nmol/ml; p < 0.05). Total cholesterol decreased in both groups
      containing pectin compared to their respective diets without supplementation
      (70.10 +/- 10.75 vs. 81.20 +/- 13.10 mg/dl; p < 0.05). CONCLUSIONS: Pectin
      consumption could decrease serum malondialdehyde and cholesterol in the diet that
      contains oxidized oil. Pectin supplementation could decrease the detrimental
      effects of thermally oxidized oil.

PMID- 22973362
TI  - Clinical features of novel 2009 influenza A (H1N1) infection in Isfahan, Iran.
AB  - BACKGROUND: During August 2009, novel H1N1 influenza virus began causing illness
      in Isfahan. Since rates of hospitalization and mortality due to the disease have
      varied widely in different countries, we described the clinical, radiologic, and
      demographic features of H1N1 hospitalized patients in a hospital in Isfahan.
      METHODS: This cross-sectional study was conducted in Alzahra Hospital during
      September 2009 to February 2010. Totally, 216 patients with confirmed, probable,
      or suspected cases of 2009 influenza A (H1N1) were admitted. RESULTS: Most
      patients were women (50.5%). Mean age of patients was 26.6 +/- 19.5 years. The
      most common complains on admission were respiratory symptoms (91.6%, n= 198),
      fever (88.4%, n = 191), myalgia (65.7%, n = 142). In addition, 120 patients (56%)
      had at least one underlying medical disorder. Thirty-six patients (16.7%) died.
      Mortality was higher in children under 5 years old (10/36, 10%) and female cases
      (63.9% of died patients). Predicting variables affecting mortality were intensive
      care unit (ICU) admission and procalcitonin (PCT) > 0.5. Antiviral treatment was
      prescribed for 200 (92.5%) of the 216 patients. CONCLUSIONS: Based on the
      findings of the present study, novel H1N1 influenza is highly prevalent among the
      youth. Moreover, it causes a relatively high morbidity rate. Therefore, people
      need to be encouraged to have vaccination against 2009 H1N1. Early diagnosis and
      treatment is related to less admission and shorter duration of hospitalization.

PMID- 22973363
TI  - The effect of shoulder core exercises on isometric torque of glenohumeral joint
      movements in healthy young females.
AB  - BACKGROUND: Strength improvement of the shoulder muscles is a major goal in
      rehabilitation or athletic conditioning programs. The purpose of this study was
      to determine the effect of shoulder core exercises on the isometric torque of
      glenohumeral joint movements. METHODS: A total of 36 healthy females with no
      history of shoulder injury enrolled in this study. Subjects were randomly
      assigned into the control group (n = 18, 22 +/- 2.19 years of age) or
      experimental group (n = 18, 21 +/- 2.05 years of age). Subjects in experimental
      group performed shoulder core exercises, using progressive resistance training,
      three times a week for six weeks. Subjects in control group performed no
      exercise. The isometric torque of shoulder movements were measured with Dynatorq
      device in isolated test positions of glenohumeral muscles at the beginning and
      after six weeks in both groups. RESULTS: shoulder core exercise training led to
      an increase in maximal isometric torques of shoulder scaption at 0 degrees  and
      90 degrees  arm elevation, external and internal rotation, horizontal adduction
      and extension movements (p < 0.001 in all instances). No significant difference
      was found between initial scores and scores after six weeks in the control group
      (p > 0.05). CONCLUSIONS: These findings indicated that shoulder core exercise
      training leads to an increase in peak torque for all glenohumeral movements that
      can be considered in glenohumeral muscles strengthening programs.

PMID- 22973364
TI  - Can NT-proBNP be used as a criterion for heart failure hospitalization in
      emergency room?
AB  - BACKGROUND: Heart failure is a common health problem with poor prognosis. The
      gold standard for diagnosis is echocardiography but it is not always reachable,
      especially in emergency conditions. NT-pro-brain natriuretic peptide (NT-proBNP)
      is a novel indicator for the diagnosis of heart failure and is being used in
      routine tests in emergency rooms. This study was conducted to compare NT-proBNP
      levels between hospitalized congestive heart failure (CHF) patients and
      outpatients. METHODS: This study was designed as a single-centre, prospective,
      and controlled trial. Blood samples and data were collected from a total of 119
      patients with shortness of breath admitted to Department of Emergency, School of
      Medicine, Marmara University. Patients were primarily diagnosed with
      decompensated heart failure according to the Framingham criteria and aged above
      18 years. A total of 92 patients were included in the study after exclusions. NT
      proBNP measurements were made by immune fluorescent method. Available data were
      compared between hospitalized patients and outpatients. RESULTS: NT-proBNP levels
      were significantly higher in hospitalized patients compared to outpatients, and
      this finding was correlated with the clinical status of the patients. The mean NT
      proBNP value of the patients was 9741.9 +/- 8973 pg/ml (range: 245-35000) while
      the mean NT-proBNP value of patients diagnosed with non-decompensated congestive
      heart failure was 688.9 +/- 284.5 pg/ml (range: 115-1450.65). CONCLUSIONS: NT
      proBNP can be used as an easy diagnostic method for congestive heart failure. A
      certain cut-off value may be determined in further multi-centre controlled trials
      with larger patient groups.

PMID- 22973365
TI  - An Iranian experience on renal allograft diseases.
AB  - BACKGROUND: Renal transplantation is the treatment of choice for most patients
      with end stage renal disease. In addition, renal biopsy is the gold standard to
      assess the causes of renal allograft dysfunction. This study was designed to
      evaluate and designate renal lesions according to Banff schema. METHODS: In this
      cross-sectional study, all renal allograft biopsies obtained from renal
      transplant patients at Alzahra and Noor referral hospitals in Isfahan during 2006
      2008 were studied. Evaluations were made according to the Banff classification
      2009. Clinical data was collected from the pathology database and analyzed using
      SPSS. RESULTS: A total number of 161 specimens were studied from 68% male and 32%
      female subjects. The donor source was living unrelated in 85%, living related
      9.9% and cadaveric in 5% of cases. Pathologic results showed 22.4% acute tubular
      necrosis (ATN), 13.7% interstitial fibrosis and tubular atrophy (IF/TA) grade II,
      9.9% IF/TA (Grade III), 6.8% acute T-cell mediated rejection (TCMR-IA), 5.6% TCMR
      IB, 5% borderline change, 5% infarction, 4.3% TCMR-IIA, 4.3% TA/IF (Grade I),
      3.7% acute antibody-mediated rejection (ABMR), 1.9% TCMR-IIB and 17.4% other
      lesions. CONCLUSIONS: The commonest causes of graft dysfunction after kidney
      transplant were IF/TA, no evidence of any specific etiology (NOS) and ATN. Living
      donors were found to be important sources for kidney transplantation in Iran.

PMID- 22973366
TI  - Comparison of the narrow band UVB versus systemic corticosteroids in the
      treatment of lichen planus: A randomized clinical trial.
AB  - BACKGROUND: Lichen planus is recognized as an inflammatory disease of the skin
      with different morphologic patterns. Different treatment modalities, including
      topical and systemic corticosteroids, methotrexate, cyclosporine, azathioprine,
      topical calcineurin inhibitors, and psoralen plus UVA (PUVA), have been suggested
      for lichen planus. Although the efficacy of narrowband UVB (NBUVB) for treatment
      of lichen planus has been shown, no randomized clinical trial has compared NBUVB
      versus systemic corticosteroids for treatment of the disease. In the current
      study, we evaluated the efficacy of NBUVB versus systemic corticosteroids in the
      treatment of the lichen planus. METHODS: Forty-six patients with confirmed
      diagnosis of lichen planus were randomly selected. The subjects were randomized
      into two groups of 23 to be treated with either systemic corticosteroids or
      NBUVB. All of the selected cases had generalized lichen planus that involved at
      least 20% of the body area and their pruritus was resistant to antihistamine
      drugs. Patients in the systemic corticosteroids group were treated with
      prednisolon 0.3 mg/kg for 6 weeks. NBUVB was performed three times a week for 6
      weeks. The maximum dose of NBUVB was 9 J/cm(2). Data regarding demographic
      characteristics of the patients was also collected. All collected data was
      analyzed using SPSS(15) and statistical tests including analysis of variance
      (ANOVA), chi-square, and t-test. RESULTS: 46 patients (23 patients in systemic
      steroid group and 23 patients in NBUVB group) were evaluated. There was a
      significant difference between the 2 groups regarding the efficacy of the
      treatment. According to chi-square test, NBUVB was significantly more effective
      than systemic steroid in treatment of generalized lichen planus (p = 0.008).
      According to the results, patient satisfaction was also significantly higher in
      the group treated with NBUVB as compared with the systemic corticosteroids (p =
      0.012). CONCLUSIONS: Overall, the results of our study and other previous studies
      showed that NBUVB may be regarded as an effective treatment for generalized
      cutaneous lichen planus. This treatment may be especially utilized when there is
      contraindication for systemic corticosteroids or other immunosuppressive drugs.

PMID- 22973367
TI  - A comparison between early maternal and neonatal complications of restrictive
      episiotomy and routine episiotomy in primiparous vaginal delivery.
AB  - BACKGROUND: Routine episiotomy is a controversial issue among gynecologists. The
      aim of this study was to compare early maternal and neonatal complications of
      restrictive episiotomy and routine episiotomy in primiparus vaginal delivery.
      METHODS: In this descriptive cross-sectional study, two groups of primiparus
      normal vaginal delivery (NVD) cases with routine and restrictive episiotomy were
      studied. Immediately and in the first 24 and 48 hours after delivery, specific
      charts were used to compare the two groups in terms of perineal laceration size,
      neonatal Apgar score and post-delivery. For data analysis, SPSS was used to
      conduct student t-test and Kruskal-Wallis test. A p-value < 0.05 was considered
      significant. RESULTS: Forty primiparus pregnant women were studied in each group.
      Episiotomy was performed in 7.5% of the restrictive group. Perineal laceration
      was measured as 3.68 +/- 0.47 cm and 1.21 +/- 1.1 in routine and restrictive
      episiotomy groups, respectively (p < 0.05). Intact perineum or first-degree
      laceration was seen in 80% of the restrictive group. However, second- and third
      degree laceration were respectively observed in 75% and 15% of the routine
      episiotomy group (p < 0.05). Pain relief (immediately, 24 and 48 hours after
      delivery) was significantly higher in the restrictive group (p < 0.05). On the
      contrary, no significant difference in Apgar scores at the first and fifth
      minutes after birth was found between the two groups (p > 0.05). CONCLUSIONS:
      Restrictive episiotomy results in low maternal complications. Therefore, avoiding
      routine episiotomy in unnecessary conditions would increase the rate of intact
      perineal and minor perineal trauma and reduce postpartum delivery pain with no
      adverse effects neither on maternal nor neonatal morbidities.

PMID- 22973368
TI  - Treatment of adenotonsillar hypertrophy: A prospective randomized trial comparing
      azithromycin vs. fluticasone.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of azithromycin vs.
      fluticasone in treatment of adenotonsillar hypertrophy (AH). METHODS: In a
      clinical trial, 39 AH patients were selected using a convenient time-based
      sequential sampling method. The subjects were randomized into two treatment
      groups. Patients in group A (fluticasone) and B (azithromycin) were respectively
      treated with fluticasone spray and azithromycin suspension for a 6-week period.
      Data regarding the grade of obstruction (based on tonsillar size), level of
      adenotonsillar hypertrophy, and obstructive sleep apnea (OSA) symptoms (including
      mouth breathing, snoring, hyponasal speech, and sleep apnea) were collected by a
      self-administrated questionnaire before treatment, as well as 1 week and 8 weeks
      after treatment. RESULTS: Twenty AH patients in group A and 19 AH patients in
      group B were studied. AH related symptoms, including mouth breathing, snoring,
      hyponasal speech and sleep apnea, improved significantly in both groups (p <
      0.05). We also found a statistically significant reduced grade of obstruction
      among patients in both groups. However, fluticasone was not effective on
      adenotonsillar hypertrophy. One week after treatment, outcomes related to apnea
      and hyponasal speech were better in group B than group A. Decreases in mouth
      breathing and snoring were not significantly different between group A and B.
      CONCLUSIONS: It could explain that though both of the improved and mentioned
      symptoms comparing within initial status, Azithromycin seems to be more effective
      than fluticasone in improving AH-related symptoms. Short term efficacy of the
      antibiotic is much significant than its long term effect.

PMID- 22973369
TI  - Forensic aspect of elder abuse: risk factors and characteristics.
AB  - BACKGROUND: This study aimed to determine the types of elder abuse, their risk
      factors and the characteristics of abusers among abused elderly people aged above
      60 years in Isfahan. METHODS: In a cross-sectional study, abused elderly
      individuals aged above 60 years that referred to the centers of competent
      jurisdiction with complaint against a person harassing them were studied during
      2008-2009. The demographic profiles of the abused and abusers were collected by
      physicians who worked in forensic medical centers, using a questionnaire. The
      type of abuse was classified as physical, emotional, sexual and neglect. RESULTS:
      The prevalence of physical, emotional and sexual abuse as well as neglect in 68
      individuals who were intentionally abused was 100%, 100%, 0% and 11.8%,
      respectively. Abused subjects were healthy, unemployed and illiterate men and
      women (similar sex distribution) with moderate monthly income who lived with
      their families, mainly in cities (p < 0.05). The abusers were mainly healthy and
      illiterate men, mostly the sons of the abused person, living in cities (p <
      0.05). Forty six (67.6%) patients had previous history of abuse, 43 (63.2%) had
      more than one previous record and in 45 ones (66.2%) the previous abuse was
      repeated. There was no relation between elder abuse and drug and alcohol abuse (p
      > 0.05). CONCLUSIONS: The findings of this study provided a sense about the
      probably high prevalence of elder abuse in our community and its related risk
      factors.

PMID- 22973370
TI  - Iranian research output in pediatrics: 1975-2007.
AB  - BACKGROUND: By providing a picture from published articles in a field,
      bibliometric studies can inform policy-makers in their challenging research
      funding decisions. In this regard, we applied bibliometric analysis to the
      Iranian pediatrics articles published in PubMed indexed journals between 1975 and
      2007. METHODS: We evaluated all pediatric articles that had been published from
      Iran in different PubMed indexed journals from 1975 to 2007. Journal data (i.e.
      date of publishing, journal name, impact factor of the journal, language),
      authors data (i.e. number of authors, international collaboration, affiliation of
      the corresponding author), and paper characteristics [i.e. type of article,
      research design, study population (neonate, infant, child, and adolescent), and
      specialty] were registered. RESULTS: During this period of time, 819 articles
      from Iran had been published in PubMed indexed journals, with a sharp increasing
      trend after 2002. Impact factors were up to 25.8. Paper had an international co
      author in 13.7%. Regarding study population, 24.1% of studies were published on
      neonates, 23.6% on infants, and the remaining 66.3% of studies were performed on
      children and adolescents from 2 to 18 years old. Infectious disease was the most
      frequent area of research, followed by public health and metabolic disease.
      Original articles were the most frequent type (89.7%) of the published articles.
      Study design was cross-sectional in 51.2%, retrospective in 36.3%, and
      prospective in 11.6%. Clinical trials made up 4.8% of the total papers.
      CONCLUSIONS: Contribution of Iran in production of pediatrics science is showing
      a sharp increase after 2002, this pattern is in parallel with other research
      fields.

PMID- 22973371
TI  - Relationships between acylated ghrelin with growth hormone, insulin resistance,
      lipid profile, and cardio respiratory function in lean and obese men.
AB  - BACKGROUND: Acylated ghrelin, biologically active form of ghrelin, activates
      growth hormone (GH) secretagogue receptor 1a and play a role in regulating of
      energy balance. The purpose of this study was to survey relationships between
      acylated ghrelin with GH, insulin resistance, lipid profile, and cardio
      respiratory function in lean and obese men. METHODS: Nineteen obese men (body
      mass index 31.0 +/- 3.5 kg/m(2), aged 27.5 +/- 5.8 year) and the same number of
      lean men (body mass index = 18.47 +/- 2.1 kg/m(2), aged 26.9 +/- 5.6 year) were
      selected if they had no experience of regular physical activity during six month
      ago. After 12 hour fasting, blood samples were collected and blood parameters as
      well as maximal oxygen uptake (as indicator of cardiorespiratory function) was
      assessed. RESULTS: Insulin levels and HOMA-IR (homeostasis model assessment of
      insulin resistance) were higher, and GH, acylated ghrelin and maximal oxygen
      uptake levels were lower, in obese versus lean men (p < 0.01). No significant
      differences were observed in systolic and diastolic blood pressure, fasting blood
      glucose, and lipid profiles between the two groups (p > 0.01). Plasma acylated
      ghrelin concentrations in obese and lean men were negatively correlated to body
      weight (r= -0.50, r= -0.43, respectively), body fat percent (r = -0.53, r = 
      0.44, respectively), body mass index (r = -0.53, r = -0.49, respectively),
      insulin (r = -0.42, r = -0.40, respectively) and HOMA-IR (r = -0.48, r = -0.45,
      respectively), and positively correlated to GH levels (r = 0.37, r = 0.31,
      respectively) and maximal oxygen uptake (r = 0.33, r = 0.31, respectively) (p <
      0.01). No significant correlations were observed between plasma acylated ghrelin
      concentrations and systolic and diastolic blood pressure, fasting blood glucose,
      and lipid profiles in both groups (p > 0.01). CONCLUSIONS: Obese and lean
      inactive young men had different levels of acylated ghrelin, GH, insulin, insulin
      resistance index, cardiorespiratory function and body fat percent. Body fat
      percent, insulin, and GH levels appear to be best determinant factors of acylated
      ghrelin levels. Also, in both obese and lean young men, higher levels of
      cardiovascular function were associated with higher levels of acylated ghrelin.

PMID- 22973372
TI  - Rapid exacerbation of multiple sclerosis following the initiation of interferon
      beta: report of nine cases.
AB  - BACKGROUND: Interferon-beta (IFN-beta) is an effective drug in multiple sclerosis
      (MS) but it may cause acute exacerbation of MS following the initiation of
      treatment. This study evaluated patients with rapid exacerbation of multiple
      sclerosis (REMS) following the initiation of IFN-beta. METHODS: We
      retrospectively reviewed the clinical records of 2350 patients with multiple
      sclerosis who started treatment with IFN-beta and were registered with Isfahan MS
      Society (IMSS). Patients with rapid exacerbation of multiple sclerosis within 24
      hours after initiation of IFN-beta treatment were selected and their demographic
      and clinical data were extracted. RESULTS: We identified nine patients with rapid
      exacerbation of multiple sclerosis following the initiation of IFN-beta. Their
      mean age at the time of treatment with IFN-beta was 37.3 +/- 6.28 years. Seven
      patients had rapid exacerbation of multiple sclerosis after initiation of IFN
      beta 1a and two patients after IFN-beta 1b. The course of disease in all of these
      patients was relapsing-remitting. However, all had converted into secondary
      progression within the first year after occurrence of rapid exacerbation of
      multiple sclerosis following the initiation of IFN-beta. CONCLUSIONS: This study
      may indicate that the effects of IFN-beta are not purely anti-inflammatory and a
      small percentage of MS patients experience rapid exacerbation of multiple
      sclerosis following the initiation of IFN-beta. Future studies are needed to
      validate our findings.

PMID- 22973373
TI  - A case of Takayasu's arteritis with pulsatile neck mass.
AB  - Takayasu's arteritis (TA), also known as pulseless disease or occlusive
      thromboaortopathy, is a form of vasculitis of unknown cause that chiefly affects
      the aorta and its major branches, most frequently in young women. We describe an
      18-year-old female with a soft and pulsatile mass in the left side of her neck.

PMID- 22973374
TI  - Filler augmentation, safe or unsafe: A case series of severe complications of
      fillers.
AB  - BACKGROUND: The growing interest in filler injection requires a more
      comprehensive knowledge about the complications of this procedure. METHODS: A
      total of 5 cases with debilitating chronic complications following filler
      injection referred to Al-Zahra hospital, Isfahan are presented in this report.
      RESULTS: The outcome of treatment for two of the cases was satisfactory. In one
      case the treatment led to failure. A case committed suicide, the remaining case
      had received vitamin E injection which caused severe necrosis and scaring.
      CONCLUSIONS: All fillers are considered foreign bodies and may provoke the immune
      system to varying degrees. Most complications are, however, caused by the
      technique of injection not the filler itself. Experience of physicians along with
      adequate knowledge about fillers and their complications can definitely guarantee
      a better outcome.

PMID- 22973375
TI  - Synchronous bilateral adrenalectomy by midline incision: A reliable method for
      treatment of hypercortisolism.

PMID- 22973376
TI  - Acute phase reactant dynamics and incidence of microvascular dysfunctions in type
      2 diabetes mellitus.

PMID- 22973377
TI  - Systemic hemodynamic and renal effects of midodrine and octreotide in cirrhotic
      patients with ascites.

PMID- 22973378
TI  - Diagnostic values of Helicobacter pylori diagnostic tests: stool antigen test,
      urea breath test, rapid urease test, serology and histology.
AB  - BACKGROUND: The purpose of this study is to compare validity of 5 diagnostic
      tests of helicobacter pylori with each other: stool antigen test, urea breath
      test (UBT), rapid urease test (RUT), serology and histology. METHODS: A total of
      94 patients who had indication of endoscopy entered the study. All of the 5 tests
      were performed for each patient. When the results of at least 2 tests were
      positive (except serology), Helicobacter pylori infection was considered to be
      positive. The sensitivity, specificity, positive predictive value, negative
      predictive value, accuracy and area under receiver operating characteristic (ROC)
      curve of these 5 tests were determined. RESULTS: The sensitivity, specificity,
      positive predictive value, negative predictive value, accuracy and area under ROC
      curve of these 5 tests are as below, respectively. HISTOLOGY: 89%, 78%, 93%, 91%,
      85% and 0.881; RUT: 93%, 75%, 95%, 94%, 86% and 0.831; serology: 50%, 54%, 46%,
      61%, 52% and 0.563; stool antigen test: 96%, 83%, 98%, 96%, 91% and 0.897; UBT:
      89%, 73%, 92%, 90%, 82% and 0.892. CONCLUSIONS: Stool antigen test is the most
      accurate test for Helicobacter pylori diagnosis before eradication of these
      bacteria.

PMID- 22973379
TI  - The mediational pathway among parenting styles, attachment styles and self
      regulation with addiction susceptibility of adolescents.
AB  - BACKGROUND: The purpose of present study was to create and test a model that
      illustrates variables that influence the development of addiction susceptibility
      and determine how different styles of parenting may indirectly influence the
      addiction susceptibility of children through the mediators of attachment style
      and self-regulation. METHODS: Using random cluster sampling, 508 adolescent high
      school boys and girls aged 14-19 years were enrolled. Data were analyzed using
      structural equations modeling (path analysis). RESULTS: The results showed that
      authoritative and permissive parenting styles were associated with secure
      attachment whereas authoritarian and neglectful parenting styles were associated
      with insecure attachment. Insecure attachment was associated with a low level of
      self-regulation whereas secure attachment was associated with a high level of
      self-regulation. We found that a low level of self-regulation increased the
      adolescent's addiction susceptibility whereas a high level of self-regulation
      decreased their addiction susceptibility. CONCLUSIONS: The findings of present
      study suggest the authoritative and permissive parenting styles as the most
      efficient styles and authoritarian and neglectful parenting styles as the most
      inefficient styles in terms of addiction susceptibility. Accordingly, efficient
      parenting style training to parents should be the main goal of drug demand
      reduction program.

PMID- 22973380
TI  - The role of ultrasonography in primary congenital hypothyroidism.
AB  - BACKGROUND: The aim of this study was to compare the usefulness of
      ultrasonography and scintigraphy in diagnosing the etiology of primary congenital
      hypothyroidism (CH). METHODS: The newborns that were examined by both thyroid
      scintigraphy and ultrasonography during CH screening program in Isfahan were
      included in this study. The ultrasonographic findings were compared with the
      scintigraphic findings and the sensitivity and specificity of the ultrasonography
      was determined. RESULTS: During this study, 102 CH newborns were studied.
      According to the ultrasonographic results, 61.8%, 26.5%, 2.9% and 8.8% of them
      had normal thyroid gland, agenesia, ectopia and hypoplasia, respectively, and
      according to scintigraphic results, 55.9%, 35.3% and 8.8% of them had normal
      thyroid gland, agenesia and ectopia, respectively. Ultrasound detected
      sensitivity, specificity, positive predictive value, negative predictive value,
      and positive and negative likelihood ratio were 77%, 92%, 89%, 84%, 9.6 and 0.25,
      respectively. The sensitivity and specificity of ultrasonography compared with
      thyroid scintigraphy in diagnosis of thyroid gland ectopia was 33% and 100%,
      respectively. CONCLUSIONS: Though thyroid ultrasonography failed to diagnose 67%
      of ectopic cases and nonfunctioning thyroid gland, it had the ability to
      determine the anatomy of thyroid gland. So, considering some limitations of
      scintigraphy, we concluded that ultrasonography is a relatively appropriate
      imaging tool for diagnosing CH etiologies, especially in the initial phase of CH
      screening.

PMID- 22973381
TI  - A randomized comparative trial of combinational methods for preventing post
      spinal hypotension at elective cesarean delivery.
AB  - BACKGROUND: Various methods have been applied to prevent maternal hypotension
      after spinal anesthesia for cesarean delivery. We compared the efficacy of three
      combinational methods in this regard in the current study. METHODS: In this
      randomized comparative trial, 150 candidates of elective cesarean delivery under
      spinal anesthesia were assigned to three groups: crystalloid preload and leg
      bandage, colloid preload and leg bandage, and ephedrine and leg bandage. Maternal
      hemodynamic changes during 60 minutes after spinal injection and neonatal
      condition were compared among the groups. RESULTS: The cumulative incidence of
      hypotension was 54%, 64%, and 36% in groups 1 to 3, respectively (p = 0.018).
      Spinal injection to hypotension interval was similar among the groups (p =
      0.828). Heart rate in group 3 was significantly lower at the most time measures
      after anesthesia compared with the other two groups (p < 0.05 to <0.001).
      Regarding neonatal outcomes, the interval between the birth and the first breath
      was longer and the Apgar score at minute 1 was lower in group 3 compared with the
      other groups (p < 0.001 and 0.038, respectively) but it was not clinically
      important. Umbilical cord blood pH was similar among the three groups (p =
      0.248). CONCLUSIONS: Among the three studied methods, administration of ephedrine
      plus bandage of the lower extremities was the most effective one in reducing the
      incidence of post-spinal hypotension. The groups were not clinically different
      concerning the effect of treatment on newborn health.

PMID- 22973382
TI  - The analgesic effect of midazolam when added to lidocaine for intravenous
      regional anaesthesia.
AB  - BACKGROUND: Midazolam has analgesic properties. The aim of the present study was
      to assess the analgesic effect of midazolam when added to lidocaine in
      intravenous regional anesthesia (IVRA). METHODS: Sixty patients undergoing hand
      surgery were randomly allocated into two groups to receive 3 mg/kg 2% lidocaine
      diluted with saline to a total volume of 40 mL in the control group (group
      lidocaine saline ~ LS, n=30) or 50 MUg/kg midazolam plus 3 mg/kg 2% lidocaine
      diluted with saline to a total volume of 40 mL in the midazolam group (group
      lidocaine midazolam ~ LM, n=30). Before and after the tourniquet application,
      hemodynamic variables, tourniquet pain, sedation, and analgesic use were
      recorded. RESULTS: Shortened sensory and motor block onset time [4.20 (0.84) vs.
      5.94 (0.83) min, p = 0.001 and 6.99 (0.72) vs. 9.07 (0.99) min, p = 0.001 in LM
      and LS groups, respectively], prolonged sensory and motor block recovery times
      [8.41 (0.94) vs. 5.68 (0.90) min, p = 0.001 and 11.85 (1.18) vs. 7.06 (0.82) min,
      p = 0.001 in LM and LS groups, respectively], shortened visual analog scale (VAS)
      scores of tourniquet pain (p < 0.05), and improved quality of anesthesia were
      found in group LM (p < 0.05). VAS scores were lower in group LM in the
      postoperative period (p = 0.001). Postoperative analgesic requirements were
      significantly smaller in group LM (p = 0.001). CONCLUSIONS: The addition of 50
      MUg/kg midazolam to lidocaine for IVRA shortens the onset of sensory and motor
      block, and improves quality of anesthesia and perioperative analgesia without
      causing side effects.

PMID- 22973383
TI  - Application of BASNEF educational model for nutritional education among elderly
      patients with type 2 diabetes: improving the glycemic control.
AB  - BACKGROUND: The objective of this study was to determine the effects of
      nutritional educational program on glycemic control of elderly patients with type
      2 diabetes. METHODS: In this parallel randomized controlled educational trial,
      100 diabetic elderly patients (>=60 years) were chosen (50 in control and 50 in
      test group). Nutrition education based on beliefs, attitudes, subjective norms
      and enabling factors (BASNEF model) was conducted. Dietary intake and glycemic
      indices as well as the components of the BASNEF model were assessed. The four 70
      minute educational sessions were conducted in one month. Three months after
      training intervention, questionnaire was completed again and blood tests were
      performed. RESULTS: Increased intake in the mean daily servings of fruits (0.91+/
      0.82 vs. 0.17+/-0.79; p < 0.001), vegetables (0.87+/-0.86 vs. 0.03+/-1; p <
      0.001) and dairy (0.35+/-0.52 vs. and 0.12+/-0.76; p < 0.001) were reported in
      the intervention group compared to the control group (p < 0.001). The amount of
      fruits, vegetables and dairy increased in the intervention group at the end of
      the study (p < 0.001). However, it was not significantly changed in the control
      group. HbA1c and fasting blood sugar (FBS) levels decreased significantly in the
      interventional group compared to the control group (p < 0.001). Comparing the
      amount of FBS and HbA1c at the end of the study with the baseline measurements
      showed significant reduction in interventional group (p < 0.001). However, there
      was no significant change in control group in this regard. CONCLUSIONS: BASNEF
      based nutritional educational intervention improved dietary intakes as well as
      glycemic control, 3 months after intervention.

PMID- 22973384
TI  - The comparative study of epidural levobupivacaine and bupivacaine in major
      abdominal surgeries.
AB  - BACKGROUND: Opioid and local anesthetic infusion by an epidural catheter is
      widely used as a postoperative pain management method after major abdominal
      surgeries. There are several agents nowadays to provide sufficient analgesia. The
      agents which cause less side effects but better quality of analgesia are more
      valuable. We aimed to postoperatively compare the analgesic, hemodynamic and
      arrhythmogenic effects of epidural levobupivacaine-fentanyl and bupivacaine
      fentanyl solutions. METHODS: Fifty patients were scheduled to undergo major
      abdominal surgery in this clinical trial. The parameters were recorded pre- and
      post-operatively. In Group I (n=25), bupivacaine with fentanyl solution and in
      Group II (n=25), levobupivacaine with fentanyl solution was infused via epidural
      patient-controlled analgesia (PCA). According to the preoperative and
      postoperative holter recording reports, the arrhythmogenic effects were examined
      in four catagories: ventricular arrhythmia (VA), supraventricular arrhythmia
      (SVA), atrioventricular conduction abnormalities and pauses longer than two
      seconds. RESULTS: Mean visual analog scale (VAS) values of groups did not differ
      at all time. They were 6 at the end of the surgery (0. Min, p = 0.622). The
      scores were 5 in Group I and 4 in Group II in 30. min (p = 0.301). The frequency
      of SVA was higher in bupivacaine group. CONCLUSIONS: The results of our study
      suggest that same concentration of epidural levobupivacaine and bupivacaine with
      fentanyl provide stable postoperative analgesia and both were found safe for the
      patients undergoing major abdominal surgery.

PMID- 22973385
TI  - Effects of hypertension on hemodynamic response and serum nitrite concentration
      during graded hemorrhagic shock in rats.
AB  - BACKGROUND: Hypertensive patients have higher morbidity and mortality from
      hemorrhage. In this study, we investigated hemodynamic responses and serum
      nitrite concentrations during graded hemorrhagic shock and resuscitation in
      hypertensive (HT) and normotensive (NT) rats. METHODS: Thirteen male rats were
      divided into two groups, namely HT (n = 6) and NT (n = 7). Hypertension was
      induced by deoxycorticosterone acetate (DOCA)-salt method in uninephrectomized
      rats. After 8 weeks, graded hemorrhagic shock was induced during 34 minutes in
      four steps separated by 8-minute intervals (totally 16 ml/kg). The animals were
      kept in this condition for 120 minutes (shock period). Then, they were
      resuscitated with blood withdrawal. Mean arterial pressure (MAP) and heart rate
      (HR) were measured throughout the experiment. Blood samples were taken before and
      after shock induction and at the end of the shock period. RESULTS: HT rats
      experienced more MAP and HR reduction during the shock period and less
      improvement of hemodynamic response after resuscitation compared with the NT
      group (p < 0.05). The survival rate 72 hours post-hemorrhage in the HT group was
      significantly lower than the NT group (16.7% vs. 71.4%, respectively) (p < 0.05).
      Serum nitrite level in HT animals was lower than the NT group (2.45 +/- 0.18 vs.
      3.35 +/- 0.26 ?mol/lit, respectively; p < 0.05). In addition, it increased during
      the shock period in both NT and HT groups (p > 0.05). CONCLUSIONS: More reduction
      of MAP after hemorrhagic shock, less improvement of MAP and HR after
      resuscitation and low survival rate in HT animals suggested the impairment of
      cardiovascular system adaptation of HT animals during blood loss and it should be
      considered in management of hypertensive subjects.

PMID- 22973386
TI  - The comparison effects of intra-articular injection of different opioids on
      postoperative pain relieve after arthroscopic anterior cruciate ligament
      reconstruction: A randomized clinical trial study.
AB  - BACKGROUND: Pain after knee surgery, if not relieved, it would lead to a more
      severe and prolonged pain that can delay the patients recovery and
      rehabilitation. The effect of pain relief by some drugs after intra-articular
      injection has been shown. This study compared the effect of intra-articular
      injection of opioids (morphine, pethidine, methadone, and tramadol) on
      postoperative relieving pain after arthroscopic anterior cruciate ligament (ACL)
      reconstruction. METHODS: 150 candidate patients for knee arthroscopic ACL
      reconstruction were randomly enrolled into five groups. At the end of the
      procedure, all patients in each group received a joint injection solution
      including 9.5 millimeters bupivacaine with 1:200,000 epinephrine. The remaining
      0.5 milliliters of syringe capacity was filled with one of the five solutions
      listed below: methadone group I: 5 mg methadone, morphine group II: 5 mg
      morphine, pethidine group III: 37.5 mg pethidine, tramadol group IV: 100 mg
      Tramadol, and control group V: 0.5 ml normal saline. Afterwards, any drug further
      administered to the patients based on need was recorded, and the morphine
      equivalent for all drugs was calculated. Patients need to narcotic drugs during
      the first twelve hours of hospitalization and pain scores were recorded. After
      data gathering, they were analyzed by SPSS 16 software with chi-Square, Kruskal
      Wallis and ANOVA statistical tests. RESULTS: The highest and the lowest
      significant pain intensity were seen in placebo and morphine groups,
      respectively, in the first, second and third 4 hours after surgery. There were
      significant differences among the groups for need to analgesics. In other words,
      placebo group needed the highest dosage of analgesics and morphine and methadone
      groups needed the lowest dosage of analgesics. Morphine and methadone groups had
      maximum and minimum response to pain, respectively, in the first, second and
      third 4 hours after surgery. CONCLUSIONS: Administering 5 mg intra-articular
      morphine after arthroscopic ACL reconstruction is a valuable choice and is
      recommended to be added to other local anesthetics administrated drugs after this
      procedure.

PMID- 22973387
TI  - Is Tokuhashi score suitable for evaluation of life expectancy before surgery in
      Iranian patients with spinal metastases?
AB  - BACKGROUND: One of the most important selection criteria for spinal metastases
      surgery is life expectancy and the most important system for this prediction has
      been proposed by Tokuhashi. The aim of this study was to evaluate predictive
      value of the Tokuhashi score for life expectancy in Iranian patients with spinal
      metastases one year after diagnosis. METHODS: From February 2007 to March 2009,
      of 180 patients suffering spinal metastatic tumors, 71 patients were excluded.
      This left a study population of 109 patients with known malignant metastases to
      spine (56 females and 53 males; mean age, 57 +/- 12 years). Tokuhashi revised
      evaluation system for the prognosis of metastatic spinal tumors was used for all
      patients. The survival period predicted by this system for the prognosis and the
      actual survival period after 1 year follow up were evaluated. RESULTS: The
      predicted survival according to Tokuhashi prognostic scoring system was less than
      6 months in 38(34.9%) patients, 6-12 months in 39(35.8%) patients and 1 year or
      more in 32(29.4%) patients. 39 (35.8%) patients died at first six-month of the
      follow up, 28(25.7%) patients at the second six-month period and 42(38.5%)
      patients were alive at the end of the year. There was no significant difference
      between predicted and actual survival time (p = 0.116). CONCLUSIONS: Present
      study showed that the Tokuhashi revised scoring system may be practicable and
      highly predictive preoperative scoring system for patients with spinal metastases
      in Iran.

PMID- 22973388
TI  - Comparison of Q-Switched 1064-nm Nd: YAG laser and fractional CO2 laser
      efficacies on improvement of atrophic facial acne scar.
AB  - BACKGROUND: Acne scarring is treatable by a variety of modalities. Ablative
      carbon dioxide laser (ACL), while effective, is associated with undesirable side
      effect profiles. Newer modalities using the principles of fractional
      photothermolysis (FP) produce modest results than traditional carbon dioxide
      (CO(2)) lasers but with fewer side effects. A novel ablative CO(2) laser device
      use a technique called ablative fractional resurfacing (AFR), combines CO(2)
      ablation with a FP system. This study was conducted to compare the efficacy of Q
      switched 1064-nm Nd: YAG laser and that of fractional CO(2) laser in the
      treatment of patients with moderate to severe acne scarring. METHODS: Sixty four
      subjects with moderate to severe facial acne scars were divided randomly into two
      groups. Group A received Q-Switched 1064-nm Nd: YAG laser and group B received
      fractional CO(2) laser. Two groups underwent four session treatment with laser at
      one month intervals. Results were evaluated by patients based on subjective
      satisfaction and physicians' assessment and photo evaluation by two blinded
      dermatologists. Assessments were obtained at baseline and at three and six months
      after final treatment. RESULTS: Post-treatment side effects were mild and
      transient in both groups. According to subjective satisfaction (p = 0.01) and
      physicians' assessment (p < 0.001), fractional CO(2) laser was significantly more
      effective than Q- Switched 1064- nm Nd: YAG laser. CONCLUSIONS: Fractional CO2
      laser has the most significant effect on the improvement of atrophic facial acne
      scars, compared with Q-Switched 1064-nm Nd: YAG laser.

PMID- 22973389
TI  - A comparative study of the effectiveness of nonattendance and workshop education
      of primary school teachers on their knowledge, attitude and function towards ADHD
      students in Isfahan in 2010.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common
      childhood behavioral disorder causing hyperactivity, attention deficit and
      education decline among students. The teachers may not have enough knowledge
      about this disorder and are in a real need in this field. Teachers' education is
      one of the ways to get knowledge about this disorder. Nowadays, finding a way
      like a short term nonattendance education method is highly in demand. Therefore,
      the aim of the study was to compare effectiveness of nonattendance and workshop
      education of primary school teachers on their knowledge, attitude, and function
      towards ADHD students. METHODS: Sixty seven primary school teachers from the
      First Districts of Education Department of Isfahan were randomly selected and put
      into two groups of workshop education (33 participants) and nonattendance
      education (34 participants). At first, both groups filled demographic date
      questionnaires and then, were given a pretest. Post tests were given after a two
      day education in workshop group and after ten days in nonattendance group who had
      studied the related booklet. Finally, the mean post test scores of knowledge,
      attitude and knowledge of function were compared between the two groups using
      ANCOVA analysis. RESULTS: After intervention, the mean scores of knowledge
      between the two groups was not significantly different whereas the mean scores of
      attitude and the mean scores of knowledge of function showed a significant
      difference between the two groups. CONCLUSIONS: Nonattendance education was as
      effective as workshop education in promotion of teachers' knowledge, but workshop
      education was more effective in attitude change and promotion of teachers'
      knowledge of function about dealing with ADHD students.

PMID- 22973390
TI  - The key stakeholders' opinions regarding university counseling centers: An
      experience from Iran.
AB  - BACKGROUND: Student counseling centers are responsible for physical, mental and
      social health of university students. Therefore, this study was conducted to
      assess the key stakeholders' opinions on different aspects of the activities
      performed in these centers. METHODS: This qualitative study used focus group
      discussion. Key stakeholders including university students and key informants
      from nine randomly selected medical universities participated in the study. After
      data saturation, thematic analysis was conducted. Themes were drawn out through
      constant comparative method. RESULTS: Based on 243 extracted codes and through
      comparative analysis, four categories were determined, namely students' need for
      students counseling centers, successes and limitations of student counseling
      centers, student counseling services priorities, and suggestions for service
      promotion. CONCLUSIONS: According to stakeholders' opinions, youth participation
      in needs assessment and priority setting processes in real-based situations leads
      to better performance of counseling services. Empowering the counselors is
      another point required for better outcomes. In addition, strategic planning and
      monitoring, along with evaluation of programs, could promote the provided
      services.

PMID- 22973391
TI  - A comparison between subpleural patient-controlled analgesia by bupivacaine and
      intermittent analgesia in post-operative thoracotomy: A double-blind randomized
      clinical trial.
AB  - BACKGROUND: The efficacy of subpleural analgesia to reduce postoperative pain
      intensity in patients after lateral thoracotomy is controversial. In this study,
      we demonstrated the efficacy of two types of subpleural analgesia. METHODS: This
      prospective, controlled, randomized, double-blind trial was performed in
      Department of Thoracic Surgery of Alzahra Hospital associated with Isfahan
      University of Medical Sciences from June 2009 until August 2010. After
      posterolateral thoracotomy and admission to the ICU, patients were randomly
      assigned into two groups of subpleural patient-controlled analgesia (SPCA) (0.02
      cc/kg/h of 0.5% bupivacaine) and subpleural intermittent analgesia (SIA)
      (0.1cc/kg/6h of 0.5% bupivacaine). The data regarding age, sex, visual analog
      scale (VAS) (at 8, 16 and 24 hours after initiation of analgesia), morphine
      consumption, systemic adverse effects, length of ICU and hospital stay,
      complications, public health service (PHS) criteria, and cost was recorded. Data
      was analyzed by Mann-Whitney U-test, repeated measured test, chi-square test and
      the Fisher's exact test. A p < 0.05 was considered significant. RESULTS: The
      study population consisted of 90 patients. There were no significant differences
      in sex, age, weight, intraoperative analgesics, duration of one-lung ventilation,
      and adverse effects between the SPCA and SIA groups. Although pain scores were
      significantly reduced at 16 hours after the first subpleural instillation of
      bupivacaine 0.5% with patient-controlled analgesia, comparison between mean pain
      scores in the two groups at 8 and 24 hours after the first subpleural
      instillation of bupivacaine 0.5% revealed no significant difference. In addition,
      no significant difference was found in VAS scores at the three evaluated times (p
      < 0.05). CONCLUSIONS: Optimal use of SPCA bupivacaine for postoperative pain
      treatment is more effective in pain reduction than SIA bupivacaine. The
      consumption rate of opioid and bupivacaine was also decreased in SPCA group.

PMID- 22973392
TI  - The effects of acupuncture on the inner ear originated tinnitus.
AB  - BACKGROUND: Tinnitus is a chronic and bothering problem which in some patients
      may lead to some psychological reactions. While tinnitus may be caused due to
      some definable structural abnormalities, sometimes no structural etiologic defect
      can be found. This study aimed to evaluate the therapeutic effects of acupuncture
      on the inner ear originated tinnitus in the latter mentioned group. METHODS: This
      prospective clinical trial study has been done in Alzahra and Kashani hospitals
      in Isfahan, Iran during 2010-2011. Simple sampling was used to select patients
      who were then divided into two groups of true acupuncture group and placebo
      group. The number of patients in each group was 27. The hospital anxiety and
      depression scale (HADS), tinnitus severity index questionnaire, and tinnitus
      loudness scale were completed by the patients. Two latter questionnaires were
      completed again after the 5th and 10th sessions of acupuncture treatment. The
      case group was treated with effective acupuncture with true acupuncture needles
      while the control group was treated ineffectively, i.e. similar to the usual
      acupuncture method but with fake needles. Independent t-test was used to compare
      the mean of tinnitus severity index and loudness scores between the two groups.
      We also used repeated measures ANOVA test to compare the mean of tinnitus
      severity index and loudness for different assessments in either group. RESULTS:
      After the 5th and 10th sessions of treatment, the mean of tinnitus severity index
      reduced significantly only in the case group (p = 0.002, and p = 0.001,
      respectively). In addition, the quality of life in the case group also improved
      after the treatment. Moreover, the mean of tinnitus loudness also reduced
      significantly only in the case group after 5 and10 sessions of treatment (p =
      0.001, and p < 0.001, respectively). CONCLUSIONS: It seems that acupuncture can
      improve tinnitus in some selected patients.

PMID- 22973393
TI  - Crown-rump length discordance in twins in the first trimester and its correlation
      with perinatal complications.
AB  - BACKGROUND: A difference more than 15-40% in birth weight of twins can predict
      perinatal complications. As significant difference in twins growth has a very
      important effect on pregnancy and perinatal complications, this study aimed to
      evaluate crown-rump length discordance (DeltaCRL) in the first trimester of
      pregnancy and its correlation with perinatal complications. METHODS: A total
      number of 118 women in the first trimester of twin pregnancy underwent ultrasound
      examination to measure DeltaCRL. Then, at the time of delivery, perinatal
      complications in twins were recorded and the correlation between DeltaCRL and
      perinatal complications were evaluated. RESULTS: Among 118 studied mothers with
      twin pregnancy, DeltaCRL was normal (< 11%) in 96 cases (81.4%) and high (>= 11%)
      in 22 cases (18.6%). Birth weight discordance was normal (< 20%) in 103 cases
      (87.3%) and above normal (>= 20%) in 15 cases (12.7%). The results revealed a
      significant correlation between higher frequency of small for gestational age
      (SGA) and high DeltaCRL (more than 11%) (p = 0.01). CONCLUSIONS: Our study
      concluded that SGA has a significant relationship with high DeltaCRL (> 11%).

PMID- 22973394
TI  - Epidemiology and trend of cancer in Isfahan 2005-2010.
AB  - BACKGROUND: Cancer incidence rate is increasing in the world particularly in
      developing countries. The awareness regarding cancer incidence and distribution
      helps policy makers and researchers to design comprehensive plan for controlling
      cancer. The aim of this study was to determine the incidence rate and trend of
      cancer in Isfahan area, one of the most importance provinces of Iran. METHODS:
      Data of Isfahan cancer registry were derived from 2005 to 2010. Direct
      standardization through world standard population produced by the world health
      organization was used and adjusted standard rate (ASR) was calculated. The
      Poisson regression analysis was employed to estimate cancer incidence trend
      during 5 years. RESULTS: The new cases of cancer were 24771 patients from 2005 to
      2010. Mean age of these patients was 56.1 +/- 18.0 years and 54.6% were male.
      Male patients were approximately 7 years older than females. The most frequent
      cancer was gastrointestinal in men and breast cancer in women. The rate of cancer
      increased approximately 4 per 1000 population and incidence rate ratio (IRR) was
      1.004 (95%CI: 1.002-1.005). CONCLUSIONS: The rate of cancer is increasing rapidly
      in Isfahan province. Cancer control and comprehensive prevention plan for Isfahan
      is necessary.

PMID- 22973396
TI  - Rosai-Dorfman Disease with nodal and extranodal involvements: A case report.
AB  - Rosai-Dorfman disease (RDD) is a rare lymphoproliferative disorder with nodal and
      extranodal involvements. Here we report a case of RDD in a 15-year-old female who
      presented with epigastric pain, fatigue, Raynaud phenomenon in fingers,
      submandibular lymphadenopathy, proptosis, hepatosplenomegaly, and round shape
      painless patches on the extensor surfaces. Histological examination of the
      submandibular lymph nodes and skin biopsy demonstrated evidences of RDD. Patient
      was treated with prednisone and thereafter, with azathioprine. After one year,
      prednisone was discontinued and all of the symptoms and signs, except proptosis,
      were resolved. This report highlights the extranodal manifestations of RDD. The
      presentation, differential diagnosis, and treatment are discussed.

PMID- 22973397
TI  - Prostate-specific antigen in females: A new tool?

PMID- 22973395
TI  - Overweight, air and noise pollution: Universal risk factors for pediatric pre
      hypertension.
AB  - Pediatric pre-hypertension (pre-HTN) has a complex multifactorial etiology.
      Although most cases are secondary to other disorders, a substantial number of
      children and adolescents have primary or essential HTN and pre-HTN. The gene-gene
      and gene-environment interactions should be considered in this context. The
      strong relationship of pre-HTN with environmental factors such as air pollution,
      noise pollution and passive smoking and obesity suggest that its prevalence will
      be escalating.Exposure to ambient particulate matters may increase blood pressure
      (BP) within hours to days. The underlying biologic pathways include autonomic
      nervous system imbalance and arterial vascular dysfunction or vasoconstriction
      because of systemic oxidative stress and inflammation. Likewise, tobacco smoke
      exposure of pregnant mothers increases systolic BP of their offspring in early
      infancy. Parental smoking also independently affects systolic BP among healthy
      preschool children. Noise exposure, notably in night, is associated with
      catecholamine secretion, increased BP and a pre-HTN state even in pre-school age
      children.Excess weight is associated with dysfunction of the adipose tissue,
      consisting of enlarged hypertrophied adipocytes, increased infiltration by
      macrophages and variations in secretion of adipokines and free fatty acids. These
      changes would result in chronic vascular inflammation, oxidative stress,
      activation of the renin-angiotensin-aldosterone system and sympathetic response,
      and ultimately to pre-HTN from childhood.Prevention and control of the modifiable
      risk factors of pre-HTN from prenatal period can have long-term health impact on
      primordial and primary prevention of chronic non-communicable diseases. This
      review presents a general view on the diagnosis, prevalence and etiology of pre
      HTN along with practical measures for its prevention and control.

PMID- 22973398
TI  - Complement factor C7 contributes to lung immunopathology caused by Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) remains a significant global health burden
      despite the availability of antimicrobial chemotherapy. Increasing evidence
      indicates a critical role of the complement system in the development of host
      protection against the bacillus, but few studies have specifically explored the
      function of the terminal complement factors. Mice deficient in complement C7 and
      wild-type C57BL/6 mice were aerosol challenged with MTB Erdman and assessed for
      bacterial burden, histopathology, and lung cytokine responses at days 30 and 60
      post-infection. Macrophages isolated from C7 -/- and wild-type mice were
      evaluated for MTB proliferation and cytokine production. C7 -/- mice had
      significantly less liver colony forming units (CFUs) at day 30; no differences
      were noted in lung CFUs. The C7 deficient mice had markedly reduced lung
      occlusion with significantly increased total lymphocytes, decreased macrophages,
      and increased numbers of CD4+ cells 60 days post-infection. Expression of lung
      IFN-gamma and TNF-alpha was increased at day 60 compared to wild-type mice. There
      were no differences in MTB-proliferation in macrophages isolated from wild-type
      and knock-out mice. These results indicate a role for complement C7 in the
      development of MTB induced immunopathology which warrants further investigation.

PMID- 22973399
TI  - A standardized chinese herbal decoction, kai-xin-san, restores decreased levels
      of neurotransmitters and neurotrophic factors in the brain of chronic stress
      induced depressive rats.
AB  - Kai-xin-san (KXS), a Chinese herbal decoction being prescribed by Sun Simiao in
      Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma,
      Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat
      stress-related psychiatric disease with the symptoms of depression and
      forgetfulness in ancient China until today. However, the mechanism of its
      antidepression action is still unknown. Here, the chronic mild-stress-(CMS-)
      induced depressive rats were applied in exploring the action mechanisms of KXS
      treatment. Daily intragastric administration of KXS for four weeks significantly
      alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose
      consumption. In addition, the expressions of those molecular bio-markers relating
      to depression in rat brains were altered by the treatment of KXS. These KXS
      regulated brain biomarkers included: (i) the levels of dopamine, norepinephrine,
      and serotonin (ii) the transcript levels of proteins relating to neurotransmitter
      metabolism; (iii) the transcript levels of neurotrophic factors and their
      receptors. The results suggested that the anti-depressant-like action of KXS
      might be mediated by an increase of neurotransmitters and expression of
      neurotrophic factors and its corresponding receptors in the brain. Thus, KXS
      could serve as alternative medicine, or health food supplement, for patients
      suffering from depression.

PMID- 22973400
TI  - Pilot Study with regard to the Wound Healing Activity of Protein from Calotropis
      procera (Ait.) R. Br.
AB  - We provide the scientific basis for the use of Calotropis procera for treating
      skin and wound infections in traditional medicine. The aqueous extract of stem
      bark of C. procera exhibited more pronounced potent antimicrobial activity. Calo
      protein was purified and identified from the most-active aqueous extracts of C.
      procera and showed broad-spectrum activity. Calo-protein inhibited the growth of
      S. aureus and E. aerogenes effectively at 25 MUg/ml concentration. Mice topically
      treated with Calo-protein revealed significant wound healing after 14 days
      comparable to fusidic acid (FA) as positive control. This protein was devoid of
      cytolytic effect even at higher concentrations on skin cells after 24 h. Further
      investigation of this Calo-protein of C. procera on bacterial inhibition may
      provide a better understanding of the scientific basis and justification for its
      use in traditional medicine.

PMID- 22973401
TI  - Hepatoprotective Activity of Elephantopus scaber on Alcohol-Induced Liver Damage
      in Mice.
AB  - Elephantopus scaber has been traditionally used as liver tonic. However, the
      protective effect of E. scaber on ethanol-induced liver damage is still unclear.
      In this study, we have compared the in vivo hepatoprotective effect of E. scaber
      with Phyllanthus niruri on the ethanol-induced liver damage in mice. The total
      phenolic and total flavanoid content of E. scaber ethanol extract were determined
      in this study. Accelerating serum biochemical profiles (including AST, ALT, ALP,
      triglyceride, and total bilirubin) associated with fat drop and necrotic body in
      the liver section were observed in the mice treated with ethanol. Low
      concentration of E. scaber was able to reduce serum biochemical profiles and the
      fat accumulation in the liver. Furthermore, high concentration of E. scaber and
      positive control P. niruri were able to revert the liver damage, which is
      comparable to the normal control. Added to this, E. scaber did not possess any
      oral acute toxicity on mice. These results suggest the potential effect of this
      extract as a hepatoprotective agent towards-ethanol induced liver damage without
      any oral acute toxicity effect. These activities might be contributed, or at
      least in part, by its high total phenolic and flavonoid contents.

PMID- 22973402
TI  - Inhibitory Effects of Chung Hun Wha Dam Tang (CHWDT) on High-Fat Diet-Induced
      Obesity via AMP-Activated Protein Kinase Activation.
AB  - The Chung Hun Wha Dam Tang (CHWDT) herbal combination was reported to cease
      dizziness and phlegm. However, the effect of CHWDT in obesity has not yet been
      known mechanically. Therefore, we investigated whether this CHWDT could protect
      the cells from lipogenesis, gluconeogenesis, and inflammation in both in vivo and
      in vitro. CHWDT significantly decreased body weight, epididymal and perirenal fat
      content without affecting feed intake in high-fat diet-induced obese mice model.
      Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1alpha, G6Pase,
      PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro.
      Proinflammatory cytokines like TNF-alpha and iNOS expression were reduced by
      CHWDT in both Raw264.7 macrophages and HepG2 cells. In addition, NO production
      was also significantly decreased by CHWDT in LPS-stimulated macrophages.
      Furthermore, AMPKalpha activation by CHWDT was involved in inhibition of obesity
      by reducing triglycerides production and increasing CPT1 expression. Based on all
      of the results, we suggest that CHWDT has inhibitory effects on obesity-induced
      lipogenesis, gluconeogenesis, and inflammation via AMPKalpha activation.

PMID- 22973403
TI  - Nigella sativa: A Potential Antiosteoporotic Agent.
AB  - Nigella sativa seeds (NS) has been used traditionally for various illnesses. The
      most abundant and active component of NS is thymoquinone (TQ). Animal studies
      have shown that NS and TQ may be used for the treatment of diabetes-induced
      osteoporosis and for the promotion of fracture healing. The mechanism involved is
      unclear, but it was postulated that the antioxidative, and anti-inflammatory
      activities may play some roles in the treatment of osteoporosis as this bone
      disease has been linked to oxidative stress and inflammation. This paper
      highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms
      behind these effects and their safety profiles. NS and TQ were shown to inhibit
      inflammatory cytokines such as interleukin-1 and 6 and the transcription factor,
      nuclear factor kappaB. NS and TQ were found to be safe at the current dosage for
      supplementation in human with precautions in children and pregnant women. Both NS
      and TQ have shown potential as antiosteoporotic agent but more animal and
      clinical studies are required to further assess their antiosteoporotic
      efficacies.

PMID- 22973404
TI  - Antibacterial Activity of Rhodomyrtus tomentosa (Aiton) Hassk. Leaf Extract
      against Clinical Isolates of Streptococcus pyogenes.
AB  - Ethanol extract of Rhodomyrtus tomentosa (Aiton) Hassk. leaf was evaluated for
      antibacterial activity against 47 clinical isolates of Streptococcus pyogenes.
      The extract exhibited good anti-S. pyogenes activity against all the tested
      isolates with similar minimum inhibitory concentration (MIC, 3.91-62.5 MUg mL(
      1)) and minimum bactericidal concentration (MBC, 3.91-62.5 MUg mL(-1)) ranges. No
      surviving cells were detected at 16 h after treatment with 8 * MIC of the
      extract. The extract-treated cells demonstrated no lysis and cytoplasmic leakage
      through the bacterial membrane. Electron micrographs further revealed that the
      extract did not cause any dramatic changes on the treated cells. Rhodomyrtone, an
      isolated compound, exhibited good anti-S. pyogenes activity (14 isolates),
      expressed very low MIC (0.39-1.56 MUg mL(-1)) and MBC (0.39-1.56 MUg mL(-1))
      values. Rhodomyrtus tomentosa leaf extract and rhodomyrtone displayed promising
      antibacterial activity against clinical isolates of S. pyogenes.

PMID- 22973405
TI  - Role of medicinal plants and natural products on osteoporotic fracture healing.
AB  - Popularly known as "the silent disease" since early symptoms are usually absent,
      osteoporosis causes progressive bone loss, which renders the bones susceptible to
      fractures. Bone fracture healing is a complex process consisting of four
      overlapping phases-hematoma formation, inflammation, repair, and remodeling. The
      traditional use of natural products in bone fractures means that phytochemicals
      can be developed as potential therapy for reducing fracture healing period.
      Located closely near the equator, Malaysia has one of the world's largest
      rainforests, which are homes to exotic herbs and medicinal plants. Eurycoma
      longifolia (Tongkat Ali), Labisia pumila (Kacip Fatimah), and Piper sarmentosum
      (Kaduk) are some examples of the popular ethnic herbs, which have been used in
      the Malay traditional medicine. This paper focuses on the use of natural products
      for treating fracture as a result of osteoporosis and expediting its healing.

PMID- 22973406
TI  - Pleurotus tuber-regium Polysaccharides Attenuate Hyperglycemia and Oxidative
      Stress in Experimental Diabetic Rats.
AB  - Pleurotus tuber-regium contains polysaccharides that are responsible for
      pharmacological actions, and medicinal effects of these polysaccharides have not
      yet been studied in diabetic rats. We examined the antidiabetic,
      antihyperlipidemic, and antioxidant properties of P. tuber-regium polysaccharides
      in experimental diabetic rats. Forty rats were equally assigned as diabetic high
      fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and
      DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose
      streptozotocin injections and a high-fat diet to mimic type 2 diabetes.
      Polysaccharides (1P, 2P, and 3P) were extracted from three different strains of
      P. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels
      substantially decreased, while serum insulin levels were restored by
      polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol,
      triglycerides, and low-density lipoprotein levels were significantly (P < 0.01)
      lower in polysaccharide groups. High-density lipoprotein levels were attenuated
      with polysaccharides against diabetes condition. Polysaccharides inhibited (P <
      0.01) the lipid peroxidation index (malondialdehyde), and restored superoxide
      dismutase and glutathione peroxidase activities in the liver of diabetic rats.
      The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant
      system that attenuates oxidative stress. We emphasize that P. tuber-regium
      polysaccharides can be considered as an alternative medicine to treat
      hyperglycemia and oxidative stress in diabetic rats.

PMID- 22973407
TI  - Extraction efficiency of shosaikoto (xiaochaihu tang) and investigation of the
      major constituents in the residual crude drugs.
AB  - Shosaikoto (Xiaochaihu Tang) is one of the frequently used traditional herbal
      medicines (Kampo medicines, Japan). To realize the effective use of precious
      crude drugs, we investigated the major constituents in the residual crude drugs
      after decoction and aimed for extraction efficiency of shosaikoto with regard to
      the extract, tannin content, and major constituents. We found that the residual
      crude drugs had large amounts of compounds, especially saikosaponin b(2), which
      had a 78.3% yield compared to that in the first decoction. The extraction
      efficiency increased when decoction time and volume of water increased. Both
      increases had an additive effect on the yield of the extract and saikosaponin
      b(2) in particular. We also found that the size of crude drug pieces that are
      available in Japanese markets is suitable for decoction because of quick
      permeation of water. From our study, the second decoction may be a valuable
      contribution to medical treatment and of effective use of crude drugs. Moreover,
      time and volume of water should be increased when patients have trouble in
      preparing a decoction. Our study revealing the factors that influence the
      extraction efficiency of shosaikoto will be the basis for empirical evidence
      about decocting Kampo medicine.

PMID- 22973409
TI  - Effect of low-level laser stimulation on EEG.
AB  - Conventional laser stimulation at the acupoint can induce significant brain
      activation, and the activation is theoretically conveyed by the sensory
      afferents. Whether the insensible low-level Laser stimulation outside the
      acupoint could also evoke electroencephalographic (EEG) changes is not known. We
      designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830
      nm, output power 7 mW, and operation frequency 10 Hz) to deliver insensible laser
      stimulations to the palm. EEG activities before, during, and after the laser
      stimulation were collected. The amplitude powers of each EEG frequency band were
      analyzed. We found that the low-level laser stimulation was able to increase the
      power of alpha rhythms and theta waves, mainly in the posterior head regions.
      These effects lasted at least 15 minutes after cessation of the laser
      stimulation. The amplitude power of beta activities in the anterior head regions
      decreased after laser stimulation. We thought these EEG changes comparable to
      those in meditation.

PMID- 22973408
TI  - The effects of tualang honey on bone metabolism of postmenopausal women.
AB  - Osteoporosis which is characterized by low bone mass and microarchitectural
      deterioration with a consequent increase in bone fragility can be associated with
      various stimuli such as oxidative stress and inflammation. Postmenopausal women
      are more prone to osteoporosis due to reduction in estrogen which may further
      lead to elevation of oxidative stress and lipid accumulation which will promote
      osteoblasts apoptosis. Proinflammatory cytokines are elevated following estrogen
      deficiency. These cytokines are important determinants of osteoclasts
      differentiation and its bone resorption activity. The main treatment for
      postmenopausal osteoporosis is estrogen replacement therapy (ERT). Despite its
      effectiveness, ERT, however, can cause many adverse effects. Therefore,
      alternative treatment that is rich in antioxidant and can exert an anti
      inflammatory effect can be given to replace the conventional ERT. Tualang honey
      is one of the best options available as it contains antioxidant as well as
      exerting anti-inflammatory effect which can act as a free radical scavenger,
      reducing the oxidative stress level as well as inhibiting proinflammatory
      cytokine. This will result in survival of osteoblasts, reduced osteoclastogenic
      activity, and consequently, reduce bone loss. Hence, Tualang honey can be used as
      an alternative treatment of postmenopausal osteoporosis with minimal side
      effects.

PMID- 22973410
TI  - The physical demands of the tree (vriksasana) and one-leg balance (utthita hasta
      padangusthasana) poses performed by seniors: a biomechanical examination.
AB  - Yoga is considered especially suitable for seniors because poses can be modified
      to accommodate practitioners' capabilities and limitations. In this study,
      biomechanical assessments on healthy seniors (n = 20; 70.1 +/- 3.8 yr) were used
      to quantify the physical demands, (net joint moments of force [JMOFs] and
      muscular activation in the lower extremities) associated with the performance of
      3 variations (introductory, intermediate, advanced) of 2 classical Hatha yoga
      poses - Tree and One-Leg Balance (OLB). ANOVA and Cohen's-d were used to contrast
      the postural variations statistically. The advanced (single-limb, without
      additional support) versions were hypothesized to generate the greatest demands,
      followed by the intermediate (single-limb [Tree] and bilateral-limb [OLB] with
      support) and introductory (bilateral-limb) versions. Our findings, however,
      suggest that common, long-held conceptions about pose modifications can be
      counter-intuitive. There was no difference between the intermediate and advanced
      Tree variations regarding hip and knee JMOFs in both the sagittal and frontal
      planes (P = 0.13-0.98). Similarly, OLB introductory and intermediate variations
      induced sagittal JMOFs that were in the opposite direction of the classic
      advanced pose version at the hip and knee (P < .001; d = 0.98-2.36). These
      biomechanical insights provide evidence that may be used by instructors,
      clinicians and therapists when selecting pose modifications for their yoga
      participants.

PMID- 22973411
TI  - Study of tumor growth under hyperthermia condition.
AB  - The new concept of keeping primary tumor under control in situ to suppress
      distant foci sheds light on the treatment of metastatic tumor. Hyperthermia is
      considered as one of the means for controlling tumor growth. To simulate the
      tumor growth, a continuum mathematical model has been introduced. The newest
      understanding of the Warburg effect on the cellular metabolism and diffusion of
      the nutrients in the tissue has been taken into consideration. The numerical
      results are compared with the in vivo experimental data by fitting the tumor cell
      doubling time/tumor cell growth rate under different thermal conditions. Both the
      tumor growth curve and corresponding average glucose concentration have been
      predicted. The numerical results have quantitatively illustrated the controlling
      effect on tumor growth under hyperthermia condition in the initial stage.

PMID- 22973413
TI  - Late recurrent urothelial carcinoma in the Studer neobladder: conversion to
      continent reservoir.
AB  - Bladder cancer represents a considerable issue in Egypt and the Middle East.
      Radical cystectomy and orthotopic neobladder represent the standard of care for
      managing cases with invasive bladder tumour. There are few cases reported in the
      literature considering the urothelial recurrence in the urethra, connected to
      neobladder. We are presenting a rare case of a young female patient, with an
      aggressive urothelial tumour, recurring 13-year post-radical cystectomy, and the
      Studer neobladder. Our case was managed by urethrectomy and conversion of the
      neobladder into continent reservoir, with good short-term oncological and
      functional outcomes. We can conclude that bladder cancer cases should be followed
      thoroughly throughout their life. Follow-up urethroscopy and cytology should be
      done for all cases of post-radical cystectomy, regardless of patients' symptoms.
      KEY MESSAGE: Late urothelial recurrence of post-radical cystectomy is possible
      and, in our case, happened 13 years following surgery. The Studer neobladder can
      be safely converted into continent reservoir, allowing good functional outcomes.
      Also, recurrence in the Studer neobladder can be safely managed, allowing good
      oncological outcomes, without the need for any ureteroileal interventions.

PMID- 22973412
TI  - Understanding immunology via engineering design: the role of mathematical
      prototyping.
AB  - A major challenge in immunology is how to translate data into knowledge given the
      inherent complexity and dynamics of human physiology. Both the physiology and
      engineering communities have rich histories in applying computational approaches
      to translate data obtained from complex systems into knowledge of system
      behavior. However, there are some differences in how disciplines approach
      problems. By referring to mathematical models as mathematical prototypes, we aim
      to highlight aspects related to the process (i.e., prototyping) rather than the
      product (i.e., the model). The objective of this paper is to review how two
      related engineering concepts, specifically prototyping and "fitness for use," can
      be applied to overcome the pressing challenge in translating data into improved
      knowledge of basic immunology that can be used to improve therapies for disease.
      These concepts are illustrated using two immunology-related examples. The
      prototypes presented focus on the beta cell mass at the onset of type 1 diabetes
      and the dynamics of dendritic cells in the lung. This paper is intended to
      illustrate some of the nuances associated with applying mathematical modeling to
      improve understanding of the dynamics of disease progression in humans.

PMID- 22973414
TI  - Persistent spontaneous bacterial peritonitis: a common complication in patients
      with spontaneous bacterial peritonitis and a high score in the model for end
      stage liver disease.
AB  - OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is associated with a high
      mortality rate. After antibiotic therapy, improvement in fluid polymorphonuclear
      (PMN) cell count is expected within 2 days. However, our institution recognized
      cases unresponsive to standard treatment. METHODS: To study these recalcitrant
      cases, we completed a retrospective chart review of patients admitted for SBP to
      the University of Chicago from 2002 to 2007. SBP was defined by an ascitic PMN
      cell count >=250/ml. RESULTS: Of 55 patients with SBP, 15 did not show
      improvement in fluid PMN cell count to below 250/ml with standard treatment,
      leading to a prevalence of 27%. The patients with persistent SBP were younger
      than those with nonpersistent SBP [mean (SD) 51.80 (9.84) compared with 58.13
      (8.79); p = 0.0253]. Persistent SBP had a higher serum ascites albumin gradient
      (SAAG) [median (Q1, Q3) 1.85 (1.50, 2.41) compared with 1.10 (0.60, 1.60)] and a
      higher score in the model for end-stage liver disease (MELD) [mean (SD) 27.98
      (8.09) compared with 22.22 (8.10)] than nonpersistent SBP patients; p = 0.027 and
      p = 0.023, respectively. In addition, persistent SBP patients were more likely to
      have a positive ascitic fluid culture than nonpersistent SBP patients [odds ratio
      (OR) (95% CI) 4.33 (1.21, 15.47); p = 0.024]. Importantly, in-hospital mortality
      in the persistent SBP group was 40%, compared with 22.5% in the nonpersistent SBP
      group [OR = 2.30 (0.64, 8.19); p = 0.20]. CONCLUSIONS: The risk of persistent SBP
      is nearly 40% in patients with MELD score >25, SAAG >1.5 or positive ascitic
      fluid culture. Furthermore, patients who develop persistent SBP tend to
      experience a higher mortality rate. This study underscores the importance of
      further examination of this vulnerable population.

PMID- 22973415
TI  - Management of Barrett's oesophagus and intramucosal oesophageal cancer: a review
      of recent development.
AB  - Barrett's oesophagus is the most important and recognizable precursor lesion for
      oesophageal adenocarcinoma, which is the one of the fastest growing cancers in
      the Western World. The incidence of oesophageal adenocarcinoma has increased 600%
      in the United States between 1975 and 2001 and is thought to represent a real
      increase in burden rather than a result of histologic or anatomical
      misclassification or overdiagnosis. Thus, the cancer risk in Barrett's oesophagus
      has to be managed and involves prevention (surveillance endoscopy), treating
      underlying gastroesophageal reflux disease (medically and or surgically) and
      endoscopic therapy to remove diseased epithelium in appropriate patient
      subgroups. In the last decade, new developments in imaging and molecular markers
      as well as an armamentarium of novel and effective endoscopic eradication therapy
      has become available to the endoscopist to combat this exponential rise in
      oesophageal adenocarcinoma. Paradoxically, the cancer risk in Barrett's
      oesophagus gets progressively downgraded which raises fundamental questions about
      our understanding of the known and unknown risk factors and molecular aberrations
      that are involved in the Barrett's metaplasia-dysplasia-carcinoma sequence.
      Future research has to be directed at these areas to fine tune our screening and
      surveillance programs to identify more accurately the high-risk group of
      progressors to oesophageal adenocarcinoma who would benefit most from endoscopic
      therapy.

PMID- 22973416
TI  - Trastuzumab: a novel standard option for patients with HER-2-positive advanced
      gastric or gastro-oesophageal junction cancer.
AB  - The human epidermal receptor-2 (HER-2) is amplified in up to 25% of patients with
      gastroesophageal adenocarcinomas. Although the presence of this amplification
      does not appear to confer a poor prognosis, it provides a valuable novel
      therapeutic target for this group of patients. Trastuzumab is a fully humanized
      monoclonal antibody directed at HER-2 which binds the external domain of the
      receptor and exerts its action via a combination of antibody-dependent
      cytotoxicity, reduced shedding of the extracellular domain, inhibition of
      dimerization and possibly receptor downregulation. The ToGA trial was an
      international multicentre randomized phase III study which evaluated the addition
      of trastuzumab to a cisplatin plus fluoropyrimidine chemotherapy doublet in 594
      patients with HER-2-positive advanced gastric or oesophagogastric junction
      adenocarcinoma. The combination of the antibody with chemotherapy significantly
      improved response rate, median progression-free survival and median overall
      survival without additional toxicity or adversely affecting quality of life.
      Accordingly, trastuzumab plus chemotherapy is now a standard first-line treatment
      option for patients with advanced HER-2-positive gastroesophageal cancer.
      Unfortunately, many patients with HER-2-positive cancer exhibit primary
      resistance to trastuzumab and the remainder will acquire resistance to the
      antibody; therefore, urgent investigation into novel agents which may circumvent
      resistance mechanisms is warranted. Small molecule inhibitors of HER-2, which
      commonly also target other members of the HER family of receptors, such as EGFR
      and HER-3, are currently undergoing evaluation in gastroesophageal cancer as
      first-line alternatives to trastuzumab and second-line salvage treatments for
      trastuzumab-resistant disease. Extrapolating the successful use of trastuzumab in
      the advanced disease setting, clinical trials are underway to assess the role of
      this antibody in the perioperative and adjuvant settings, where it is hoped that
      it will have a meaningful impact upon the currently poor survival rates.

PMID- 22973417
TI  - Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway:
      novel targeted therapies and advances in the treatment of colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer-related death in
      the USA, and more effective treatment of CRC is therefore needed. Advances in our
      understanding of the molecular pathogenesis of this malignancy have led to the
      development of novel molecule-targeted therapies. Among the most recent classes
      of targeted therapies being developed are inhibitors targeting the
      phosphatidylinositol 3-kinase (PI3K) signaling pathway. As one of the most
      frequently deregulated pathways in several human cancers, including CRC, aberrant
      PI3K signaling plays an important role in the growth, survival, motility and
      metabolism of cancer cells. Targeting this pathway therefore has considerable
      potential to lead to novel and more effective treatments for CRC. Preclinical and
      early clinical studies have revealed the potential efficacy of drugs that target
      PI3K signaling for the treatment of CRC. However, a major challenge that remains
      is to study these agents in phase III clinical trials to see whether these early
      successes translate into better patient outcomes. In this review we focus on
      providing an up-to-date assessment of our current understanding of PI3K signaling
      biology and its deregulation in the molecular pathogenesis of CRC. Advances in
      available agents and challenges in targeting the PI3K signaling pathway in CRC
      treatment will be discussed and placed in the context of the currently available
      therapies for CRC.

PMID- 22973420
TI  - Erratum for PMID 21180585.
AB  - Erratum to 'Possible interactions between dietary fibres and 5-aminosalicyclic
      acid' by C Henriksen, S Hansen, I Nordgaard-Lassen, J Rikardt Anderson and P
      Madsen. Therapeutic Advances in Gastroenterology (2010) 3(1) 5-9 [DOI: 10.1177/
      1756283X09347810][This corrects the article on p. 5 in vol. 3.].

PMID- 22973418
TI  - Pain management in patients with inflammatory bowel disease: insights for the
      clinician.
AB  - Abdominal pain is a common symptom in patients with inflammatory bowel disease
      (IBD) and has a profound negative impact on patients' lives. There are growing
      data suggesting that pain is variably related to the degree of active
      inflammation. Given the multifactorial etiologies underlying the pain, the
      treatment of abdominal pain in the IBD population is best accomplished by
      individualized plans. This review covers four clinically relevant categories of
      abdominal pain in patients with IBD, namely, inflammation, surgical
      complications, bacterial overgrowth, and neurobiological processes and how pain
      management can be addressed in each of these cases. The role of genetic factors,
      psychological factors, and psychosocial stress in pain perception and treatment
      will also be addressed. Lastly, psychosocial, pharmacological, and procedural
      pain management techniques will be discussed. An extensive review of the existing
      literature reveals a paucity of data regarding pain management specific to IBD.
      In addition, there is growing consensus suggesting a spectrum between IBD and
      irritable bowel syndrome (IBS) symptoms. Thus, this review for adult and
      pediatric clinicians also incorporates the literature for the treatment of
      functional abdominal pain and the clinical consensus from IBD and IBS experts on
      pharmacological, behavioral, and procedural methods to treat abdominal pain in
      this population.

PMID- 22973419
TI  - Management of hepatitis B reactivation in patients receiving cancer chemotherapy.
AB  - Hepatitis B virus (HBV) reactivation is well documented in previously resolved or
      inactive HBV carriers who receive cancer chemotherapy. The consequences of HBV
      reactivation range from self-limited conditions to fulminant hepatic failure and
      death. HBV reactivation also leads to premature termination of chemotherapy or
      delay in treatment schedules. This review summarizes current knowledge of
      management of HBV reactivation in patients receiving cancer chemotherapy. HBV
      surface antigen (HBsAg) testing should be performed in patients who require
      cancer chemotherapy. Four meta-analyses support lamivudine prophylaxis for HBV
      reactivation during chemotherapy in HBsAg-positive patients. Randomized
      controlled trials to compare different HBV antiviral agents are needed to define
      optimal regimens for the prevention and treatment of HBV reactivation in patients
      receiving cancer chemotherapy.

PMID- 22973421
TI  - Multiple sclerosis and pregnancy: experience from a nationwide database in
      Germany.
AB  - OBJECTIVE: The objective of this study was to evaluate exposure to disease
      modifying therapies (DMTs) during pregnancy in 335 pregnancies of multiple
      sclerosis (MS) patients and to further determine whether exclusive breastfeeding
      of MS mothers has any relevant influence on postpartum relapse rate. BACKGROUND:
      Only limited data are available on whether DMT exposure during pregnancy affects
      relapse rate during pregnancy or after birth. Currently, findings on beneficial
      effect of exclusive breastfeeding on MS disease course are controversially
      discussed. METHODS: We enrolled pregnant women with MS who contacted us directly
      or via their treating physicians to be included in our nationwide MS and
      pregnancy database. RESULTS: We identified 78 pregnancies under interferon-beta
      (IFNbeta) preparations, 41 under glatiramer acetate (GLAT), and 216 pregnancies
      without DMT exposure during pregnancy. As expected, annualized relapse rate (ARR)
      decreased continuously during pregnancy in nonexposed mothers (p < 0.001) to then
      increase after birth. In IFNbeta- or GLAT-exposed women this typical pattern was
      not as obvious. Congenital anomalies were within normal ranges in exposed
      pregnancies. In total, 170 women were identified who exclusively breastfed (EBF).
      Significantly reduced postpartum relapse rate during the first 3 months after
      birth were registered in the EBF group as compared with nonexclusively
      breastfeeding (NEBF) or nonbreastfeeding women (NBF) women with MS (p < 0.0001).
      Relapse rate (RR) in the year before pregnancy had been similar throughout all
      groups. We did not observe any significant differences in RR of NEBF and NBF
      women. CONCLUSION: Exclusive breastfeeding showed some beneficial effects on
      postpartum relapse rate in our cohort. Our data support that IFNbeta and GLAT do
      not seem to represent a major teratogenic risk in pregnancy.

PMID- 22973422
TI  - Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating
      spasticity.
AB  - A large proportion of patients with multiple sclerosis (MS) have spasticity,
      which has a marked impact on their quality of life. Anecdotal evidence suggests a
      beneficial effect of cannabis on spasticity as well as pain. Recently,
      randomized, double-blind, placebo-controlled studies have confirmed the clinical
      efficacy of cannabinoids for the treatment of spasticity in patients with MS.
      Based on these data, nabiximols (Sativex), a 1:1 mix of Delta-9
      tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa
      chemovars, received approval for treating MS-related spasticity in various
      countries around the globe. In this article we review the current understanding
      of cannabinoid biology and the value of cannabinoids as a symptomatic treatment
      option addressing spasticity in patients with MS.

PMID- 22973423
TI  - White matter dementia.
AB  - White matter dementia (WMD) is a syndrome introduced in 1988 to highlight the
      potential of cerebral white matter disorders to produce cognitive loss of
      sufficient severity to qualify as dementia. Neurologists have long understood
      that such a syndrome can occur, but the dominance of gray matter as the locus of
      higher function has strongly directed neurobehavioral inquiry to the cerebral
      cortex while white matter has received less attention. Contemporary neuroimaging
      has been crucial in enabling the recognition of white matter abnormalities in a
      host of disorders, and the correlation of these changes with cognitive
      performance. Comprising about half the brain, white matter is prominently or
      exclusively involved in well over 100 disorders, in each of which white matter
      dysfunction can potentially cause or contribute to dementia. Neuropsychological
      findings from ten categories of white matter disorder lead to a convergence of
      findings that document remarkable neurobehavioral commonality among the dementias
      produced. More recently, the syndrome of mild cognitive dysfunction (MCD) has
      been introduced to expand the concept of WMD by proposing a precursor syndrome
      related to early white matter neuropathology. WMD and MCD inform the
      understanding of how white matter contributes to normal and abnormal cognition,
      and the specific neuroanatomic focus of these syndromes may enhance the diagnosis
      and treatment of many disabling disorders that do not primarily implicate the
      cerebral cortex. Forming essential connections within widely distributed neural
      networks, white matter is critical for rapid and efficient information transfer
      that complements the information processing of gray matter. As neuroimaging
      continues to advance, further information on white matter structure can be
      expected, and behavioral neurology will play a central role in elucidating the
      functional significance of these emerging data. By emphasizing the contribution
      of myelinated systems to higher function, the study of white matter and cognition
      represents investigation of the basic neuroscience of human behavior.

PMID- 22973424
TI  - Herpesvirus infections of the central nervous system in immunocompromised
      patients.
AB  - Human herpesviruses may cause infections of the central nervous system during
      primary infection or following reactivation from a latent state. Especially in
      immunosuppressed patients the infection can take a life-threatening course, and
      therefore early diagnosis of herpesvirus-associated neurological diseases should
      have high priority. Clinical presentation in these patients is usually without
      typical features, making diagnosis even more challenging. Therefore general broad
      testing for different herpesviruses in cerebrospinal fluid samples is highly
      recommended. In addition, determination of the virus DNA level in the
      cerebrospinal fluid by quantitative assays seems to be of high importance to
      determine prognosis. Moreover, it might help to differentiate between specific
      virus-associated disease and unspecific presence of virus in the cerebrospinal
      fluid, especially in immunocompromised patients. Polymerase chain reaction
      analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous
      system viral infections, particularly those caused by human herpesviruses. This
      review summarizes the role human herpesviruses play in central nervous system
      infections in immunocompromised patients, with a focus on the clinical
      manifestation of encephalitis.

PMID- 22973425
TI  - Diagnosis and management of central hypersomnias.
AB  - Central hypersomnias are diseases manifested in excessive daytime sleepiness
      (EDS) not caused by disturbed nocturnal sleep or misaligned circadian rhythms.
      Central hypersomnias includes narcolepsy with and without cataplexy, recurrent
      hypersomnia, idiopathic hypersomnia, with and without long sleep time,
      behaviorally induced insufficient sleep syndrome, hypersomnia and narcolepsy due
      to medical conditions, and finally hypersomnia induced by substance intake. The
      Epworth Sleepiness Scale is a subjective tool mostly used for EDS assessment,
      while the Multiple Sleep Latency Test serves as an objective diagnostic method
      for narcolepsy and idiopathic hypersomnias. As for symptomatic therapy of EDS,
      the central nervous system stimulants modafinil and methylphenidate seem to work
      well in most cases and in narcolepsy and Parkinson's disease; sodium oxybate also
      has notable therapeutic value.

PMID- 22973426
TI  - OPTIMIZING DIAGNOSIS AND MANANGEMENT IN MILD-TO-MODERATE ALZHEIMER'S DISEASE.
AB  - Alzheimer's disease (AD) is characterized by progressive declines in cognitive
      function and ability to carry out activities of daily living; and the emergence
      and worsening of behavioral/neuropsychiatric symptoms. While there is no cure for
      AD, non-pharmacologic interventions and medications that modulate
      neurotransmission can slow symptomatic progression. Medical foods may also be
      useful as adjuncts to pharmacologic agents in AD. Medium chain triglycerides
      aimed at improving cerebral metabolism significantly improve Alzheimer's Disease
      Assessment Scale-Cognitive scores when added to ongoing pharmacotherapy in
      patients with mild-to-moderate AD. Combination of interventions, such as non
      pharmacologic treatments, pharmacotherapy, and medical foods, with complementary
      mechanisms of action may provide a rational approach that may result in maximum
      preservation of cognitive function in patients with AD.

PMID- 22973436
TI  - Pro-inflammatory cytokine regulation of P-glycoprotein in the developing blood
      brain barrier.
AB  - Placental P-glycoprotein (P-gp) acts to protect the developing fetus from
      exogenous compounds. This protection declines with advancing gestation leaving
      the fetus and fetal brain vulnerable to these compounds and potential teratogens
      in maternal circulation. This vulnerability may be more pronounced in pregnancies
      complicated by infection, which is common during pregnancy. Pro-inflammatory
      cytokines (released during infection) have been shown to be potent inhibitors of
      P-gp, but nothing is known regarding their effects at the developing blood-brain
      barrier (BBB). We hypothesized that P-gp function and expression in endothelial
      cells of the developing BBB will be inhibited by pro-inflammatory cytokines. We
      have derived brain endothelial cell (BEC) cultures from various stages of
      development of the guinea pig: gestational day (GD) 50, 65 (term ~68 days) and
      postnatal day (PND) 14. Once these cultures reached confluence, BECs were treated
      with various doses (10(0)-10(4 )pg/mL) of pro-inflammatory cytokines: interleukin
      1beta (IL-1beta), interleukin-6 (IL-6) or tumor necrosis factor- alpha (TNF
      alpha). P-gp function or abcb1 mRNA (encodes P-gp) expression was assessed
      following treatment. Incubation of GD50 BECs with IL-1beta, IL-6 or TNF-alpha
      resulted in no change in P-gp function. GD65 BECs displayed a dose-dependent
      decrease in function with all cytokines tested; maximal effects at 42%, 65% and
      34% with IL-1beta, IL-6 and TNF-alpha treatment, respectively (P<0.01).
      Inhibition of P-gp function by IL-1beta, IL-6 and TNF-alpha was even greater in
      PND14 BECs; maximal effects at 36% (P<0.01), 84% (P<0.05) and 55% (P<0.01),
      respectively. Cytokine-induced reductions in P-gp function were associated with
      decreased abcb1 mRNA expression. These data suggest that BBB P-gp function is
      increasingly responsive to the inhibitory effects of pro-inflammatory cytokines,
      with increasing developmental age. Thus, women who experience infection and take
      prescription medication during pregnancy may expose the developing fetal brain to
      greater amounts of exogenous compounds - many of which are considered potentially
      teratogenic.

PMID- 22973437
TI  - Crystallographic study of novel transthyretin ligands exhibiting negative
      cooperativity between two thyroxine binding sites.
AB  - BACKGROUND: Transthyretin (TTR) is a homotetrameric serum and cerebrospinal fluid
      protein that transports thyroxine (T4) and retinol by binding to retinol binding
      protein. Rate-limiting tetramer dissociation and rapid monomer misfolding and
      disassembly of TTR lead to amyloid fibril formation in different tissues causing
      various amyloid diseases. Based on the current understanding of the pathogenesis
      of TTR amyloidosis, it is considered that the inhibition of amyloid fibril
      formation by stabilization of TTR in native tetrameric form is a viable approach
      for the treatment of TTR amyloidosis. METHODOLOGY AND PRINCIPAL FINDINGS: We have
      examined interactions of the wtTTR with a series of compounds containing various
      substitutions at biphenyl ether skeleton and a novel compound, previously
      evaluated for binding and inhibiting tetramer dissociation, by x-ray
      crystallographic approach. High resolution crystal structures of five ligands in
      complex with wtTTR provided snapshots of negatively cooperative binding of
      ligands in two T4 binding sites besides characterizing their binding
      orientations, conformations, and interactions with binding site residues. In all
      complexes, the ligand has better fit and more potent interactions in first T4
      site i.e. (AC site) than the second T4 site (BD site). Together, these results
      suggest that AC site is a preferred ligand binding site and retention of ordered
      water molecules between the dimer interfaces further stabilizes the tetramer by
      bridging a hydrogen bond interaction between Ser117 and its symmetric copy.
      CONCLUSION: Novel biphenyl ether based compounds exhibit negative-cooperativity
      while binding to two T4 sites which suggests that binding of only single ligand
      molecule is sufficient to inhibit the TTR tetramer dissociation.

PMID- 22973438
TI  - Hepatic lipid accumulation alters global histone h3 lysine 9 and 4 trimethylation
      in the peroxisome proliferator-activated receptor alpha network.
AB  - Recent data suggest that the etiology of several metabolic diseases is closely
      associated with transcriptome alteration by aberrant histone methylation. We
      performed DNA microarray and ChIP-on-chip analyses to examine transcriptome
      profiling and trimethylation alterations to identify the genomic signature of
      nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver
      disease. Transcriptome analysis showed that steatotic livers in high-fat diet-fed
      apolipoprotein E2 mice significantly altered the expression of approximately 70%
      of total genes compared with normal diet-fed control livers, suggesting that
      hepatic lipid accumulation induces dramatic alterations in gene expression in
      vivo. Also, pathway analysis suggested that genes encoding chromatin-remodeling
      enzymes, such as jumonji C-domain-containing histone demethylases that regulate
      histone H3K9 and H3K4 trimethylation (H3K9me3, H3K4me3), were significantly
      altered in steatotic livers. Thus, we further investigated the global H3K9me3 and
      H3K4me3 status in lipid-accumulated mouse primary hepatocytes by ChIP-on-chip
      analysis. Results showed that hepatic lipid accumulation induced aberrant H3K9me3
      and H3K4me3 status in peroxisome proliferator-activated receptor alpha and
      hepatic lipid catabolism network genes, reducing their mRNA expression compared
      with non-treated control hepatocytes. This study provides the first evidence that
      epigenetic regulation by H3K9me3 and H3K4me3 in hepatocytes may be involved in
      hepatic steatosis and the pathogenesis of NAFLD. Thus, control of H3K9me3 and
      H3K4me3 represents a potential novel NAFLD prevention and treatment strategy.

PMID- 22973439
TI  - A novel animal model of partial optic nerve transection established using an
      optic nerve quantitative amputator.
AB  - BACKGROUND: Research into retinal ganglion cell (RGC) degeneration and
      neuroprotection after optic nerve injury has received considerable attention and
      the establishment of simple and effective animal models is of critical importance
      for future progress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the
      optic nerves of Wistar rats were semi-transected selectively with a novel optic
      nerve quantitative amputator. The variation in RGC density was observed with
      retro-labeled fluorogold at different time points after nerve injury. The
      densities of surviving RGCs in the experimental eyes at different time points
      were 1113.69+/-188.83 RGC/mm2 (the survival rate was 63.81% compared with the
      contralateral eye of the same animal) 1 week post surgery; 748.22+/-134.75/mm2
      (46.16% survival rate) 2 weeks post surgery; 505.03+/-118.67/mm2 (30.52% survival
      rate) 4 weeks post surgery; 436.86+/-76.36/mm2 (24.01% survival rate) 8 weeks
      post surgery; and 378.20+/-66.74/mm2 (20.30% survival rate) 12 weeks post
      surgery. Simultaneously, we also measured the axonal distribution of optic nerve
      fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and
      the variation in pupil diameter response to pupillary light reflex. All of these
      observations and profiles were consistent with post injury variation
      characteristics of the optic nerve. These results indicate that we effectively
      simulated the pathological process of primary and secondary injury after optic
      nerve injury. CONCLUSIONS/SIGNIFICANCE: The present quantitative transection
      optic nerve injury model has increased reproducibility, effectiveness and
      uniformity. This model is an ideal animal model to provide a foundation for
      researching new treatments for nerve repair after optic nerve and/or central
      nerve injury.

PMID- 22973440
TI  - Prolactin stimulates precursor cells in the adult mouse hippocampus.
AB  - In the search for ways to combat degenerative neurological disorders,
      neurogenesis-stimulating factors are proving to be a promising area of research.
      In this study, we show that the hormonal factor prolactin (PRL) can activate a
      pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro
      neurosphere assay, we found that the addition of exogenous PRL to primary adult
      hippocampal cells resulted in an approximate 50% increase in neurosphere number.
      In addition, direct infusion of PRL into the adult dentate gyrus also resulted in
      a significant increase in neurosphere number. Together these data indicate that
      exogenous PRL can increase hippocampal precursor numbers both in vitro and in
      vivo. Conversely, PRL null mice showed a significant reduction (approximately
      80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit
      in precursor proliferation was observed in vivo, indicating that in this
      situation other niche factors can compensate for a loss in PRL. The PRL loss
      resulted in learning and memory deficits in the PRL null mice, as indicated by
      significant deficits in the standard behavioral tests requiring input from the
      hippocampus. This behavioral deficit was rescued by direct infusion of
      recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult
      mouse hippocampus can be correlated with impaired learning and memory.

PMID- 22973441
TI  - Coevolution in RNA molecules driven by selective constraints: evidence from 5S
      rRNA.
AB  - Understanding intra-molecular coevolution helps to elucidate various structural
      and functional constraints acting on molecules and might have practical
      applications in predicting molecular structure and interactions. In this study,
      we used 5S rRNA as a template to investigate how selective constraints have
      shaped the RNA evolution. We have observed the nonrandom occurrence of paired
      differences along the phylogenetic trees, the high rate of compensatory
      evolution, and the high TIR scores (the ratio of the numbers of terminal to
      intermediate states), all of which indicate that significant positive selection
      has driven the evolution of 5S rRNA. We found three mechanisms of compensatory
      evolution: Watson-Crick interaction (the primary one), complex interactions
      between multiple sites within a stem, and interplay of stems and loops.
      Coevolutionary interactions between sites were observed to be highly dependent on
      the structural and functional environment in which they occurred. Coevolution
      occurred mostly in those sites closest to loops or bulges within structurally or
      functionally important helices, which may be under weaker selective constraints
      than other stem positions. Breaking these pairs would directly increase the size
      of the adjoining loop or bulge, causing a partial or total structural
      rearrangement. In conclusion, our results indicate that sequence coevolution is a
      direct result of maintaining optimal structural and functional integrity.

PMID- 22973442
TI  - Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory
      responses than Plasmodium falciparum?
AB  - BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory
      responses on exposure to different malaria parasites remains unclear. Although
      Plasmodium vivax usually causes a relatively benign disease, this parasite has
      been suggested to elicit more host inflammation per parasitized red blood cell
      than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma
      concentrations of seven cytokines and two soluble tumor necrosis factor (TNF)
      alpha receptors, and evaluated clinical and laboratory outcomes, in Brazilians
      with acute uncomplicated infections with P. vivax (n = 85), P. falciparum (n =
      30), or both species (n = 12), and in 45 asymptomatic carriers of low-density P.
      vivax infection. Symptomatic vivax malaria patients, compared to those infected
      with P. falciparum or both species, had more intense paroxysms, but they had no
      clear association with a pro-inflammatory imbalance. To the contrary, these
      patients had higher levels of the regulatory cytokine interleukin (IL)-10, which
      correlated positively with parasite density, and elevated IL-10/TNF-alpha, IL
      10/interferon (IFN)-gamma, IL-10/IL-6 and sTNFRII/TNF-alpha ratios, compared to
      falciparum or mixed-species malaria patient groups. Vivax malaria patients had
      the highest levels of circulating soluble TNF-alpha receptor sTNFRII. Levels of
      regulatory cytokines returned to normal values 28 days after P. vivax clearance
      following chemotherapy. Finally, asymptomatic carriers of low P. vivax
      parasitemias had substantially lower levels of both inflammatory and regulatory
      cytokines than did patients with clinical malaria due to either species.
      CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a
      strong inflammatory response to prevent fulminant infections, while reducing
      inflammation-related tissue damage with early regulatory cytokine responses may
      be a more cost-effective strategy in infections with the less virulent P. vivax
      parasite. The early induction of regulatory cytokines may be a critical mechanism
      protecting vivax malaria patients from severe clinical complications.

PMID- 22973443
TI  - Mortality and health outcomes in HIV-infected and HIV-uninfected mothers at 18-20
      months postpartum in Zomba District, Malawi.
AB  - BACKGROUND: Maternal morbidity and mortality among HIV-infected women is a global
      concern. This study compared mortality and health outcomes of HIV-infected and
      HIV-uninfected mothers at 18-20 months postpartum within routine prevention of
      mother-to-child transmission of HIV (PMTCT) services in a rural district in
      Malawi. METHODS: A retrospective cohort study of mother-child dyads at 18-20
      months postpartum in Zomba District. Data on socio-demographic characteristics,
      service uptake, maternal health outcomes and biometric parameters were collected.
      RESULTS: 173 HIV-infected and 214 HIV-uninfected mothers were included. HIV
      specific cohort mortality at 18-20 months postpartum was 42.4 deaths/1000 person
      years; no deaths occurred among HIV-uninfected women. Median time to death was 11
      months post-partum (range 3-19). Women ranked their health on a comparative
      qualitative scale; HIV-infected women perceived their health to be poorer than
      did HIV-uninfected women (RR 2.4; 95% CI 1.6-3.7). Perceived maternal health
      status was well correlated with an objective measure of functional status
      (Karnofsky scale; p<0.001). HIV-infected women were more likely to report minor
      (RR 3.8; 95% CI 2.3-6.4) and major (RR 6.2; 95% CI 2.2-17.7) signs or symptoms of
      disease. In multivariable analysis, HIV-infected women remained twice as likely
      to report poorer health [adjusted OR (aOR) 2.3; 95% CI 1.4-3.6], as did women
      with low BMI (aOR 2.1; 95% CI 1.1-4.0) and scoring lowest on the welfare scale
      (aOR 2.0; 95% CI 1.1-3.8). CONCLUSIONS: HIV-infected women show increased
      mortality and morbidity at 18-20 months postpartum. In our rural Malawian
      operational setting, where there is documented under-application of ART and poor
      adherence to PMTCT services, these results support attention to optimizing
      maternal participation in PMTCT programs.

PMID- 22973444
TI  - Genetical genomics identifies the genetic architecture for growth and weevil
      resistance in spruce.
AB  - In plants, relationships between resistance to herbivorous insect pests and
      growth are typically controlled by complex interactions between genetically
      correlated traits. These relationships often result in tradeoffs in phenotypic
      expression. In this study we used genetical genomics to elucidate genetic
      relationships between tree growth and resistance to white pine terminal weevil
      (Pissodes strobi Peck.) in a pedigree population of interior spruce (Picea
      glauca, P. engelmannii and their hybrids) that was growing at Vernon, B.C. and
      segregating for weevil resistance. Genetical genomics uses genetic perturbations
      caused by allelic segregation in pedigrees to co-locate quantitative trait loci
      (QTLs) for gene expression and quantitative traits. Bark tissue of apical leaders
      from 188 trees was assayed for gene expression using a 21.8K spruce EST-spotted
      microarray; the same individuals were genotyped for 384 SNP markers for the
      genetic map. Many of the expression QTLs (eQTL) co-localized with resistance
      trait QTLs. For a composite resistance phenotype of six attack and oviposition
      traits, 149 positional candidate genes were identified. Resistance and growth
      QTLs also overlapped with eQTL hotspots along the genome suggesting that: 1)
      genetic pleiotropy of resistance and growth traits in interior spruce was
      substantial, and 2) master regulatory genes were important for weevil resistance
      in spruce. These results will enable future work on functional genetic studies of
      insect resistance in spruce, and provide valuable information about candidate
      genes for genetic improvement of spruce.

PMID- 22973445
TI  - Galectin-8 promotes cytoskeletal rearrangement in trabecular meshwork cells
      through activation of Rho signaling.
AB  - PURPOSE: The trabecular meshwork (TM) cell-matrix interactions and factors that
      influence Rho signaling in TM cells are thought to play a pivotal role in the
      regulation of aqueous outflow. The current study was designed to evaluate the
      role of a carbohydrate-binding protein, galectin-8 (Gal8), in TM cell adhesion
      and Rho signaling. METHODS: Normal human TM cells were assayed for Gal8
      expression by immunohistochemistry and Western blot analysis. To assess the role
      of Gal8 in TM cell adhesion and Rho signaling, the cell adhesion and spreading
      assays were performed on Gal8-coated culture plates in the presence and the
      absence of anti-beta1 integrin antibody and Rho and Rho-kinase inhibitors. In
      addition, the effect of Gal8-mediated cell-matrix interactions on TM cell
      cytoskeleton arrangement and myosin light chain 2 (MLC2) phosphorylation was
      examined. PRINCIPAL FINDINGS: We demonstrate here that Gal8 is expressed in the
      TM and a function-blocking anti-beta1 integrin antibody inhibits the adhesion and
      spreading of TM cells to Gal8-coated wells. Cell spreading on Gal8 substratum was
      associated with the accumulation of phosphorylated myosin light chain and the
      formation of stress fibers that was inhibited by the Rho inhibitor, C3
      transferase, as well as by the Rho-kinase inhibitor, Y27632.
      CONCLUSIONS/SIGNIFICANCE: The above findings present a novel function for Gal8 in
      activating Rho signaling in TM cells. This function may allow Gal8 to participate
      in the regulation of aqueous outflow.

PMID- 22973446
TI  - Environmental Profile of a Community's Health (EPOCH): an ecometric assessment of
      measures of the community environment based on individual perception.
AB  - BACKGROUND: Public health research has turned towards examining upstream,
      community-level determinants of cardiovascular disease risk factors. Objective
      measures of the environment, such as those derived from direct observation, and
      perception-based measures by residents have both been associated with health
      behaviours. However, current methods are generally limited to objective measures,
      often derived from administrative data, and few instruments have been evaluated
      for use in rural areas or in low-income countries. We evaluate the reliability of
      a quantitative tool designed to capture perceptions of community tobacco,
      nutrition, and social environments obtained from interviews with residents in
      communities in 5 countries. METHODOLOGY/ PRINCIPAL FINDINGS: Thirteen measures of
      the community environment were developed from responses to questionnaire items
      from 2,360 individuals residing in 84 urban and rural communities in 5 countries
      (China, India, Brazil, Colombia, and Canada) in the Environmental Profile of a
      Community's Health (EPOCH) study. Reliability and other properties of the
      community-level measures were assessed using multilevel models. High reliability
      (>0.80) was demonstrated for all community-level measures at the mean number of
      survey respondents per community (n = 28 respondents). Questionnaire items
      included in each scale were found to represent a common latent factor at the
      community level in multilevel factor analysis models. CONCLUSIONS/ SIGNIFICANCE:
      Reliable measures which represent aspects of communities potentially related to
      cardiovascular disease (CVD)/risk factors can be obtained using feasible sample
      sizes. The EPOCH instrument is suitable for use in different settings to explore
      upstream determinants of CVD/risk factors.

PMID- 22973447
TI  - Differential activities of the two closely related withanolides, Withaferin A and
      Withanone: bioinformatics and experimental evidences.
AB  - BACKGROUND AND PURPOSE: Withanolides are naturally occurring chemical compounds.
      They are secondary metabolites produced via oxidation of steroids and
      structurally consist of a steroid-backbone bound to a lactone or its derivatives.
      They are known to protect plants against herbivores and have medicinal value
      including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects.
      Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar
      withanolides isolated from Withania somnifera, also known as Ashwagandha in
      Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich
      in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely
      related purified phytochemicals, Wi-A and Wi-N, showed differential activity in
      normal and cancer human cells in vitro and in vivo. We had earlier identified
      several genes involved in cytotoxicity of i-Extract in human cancer cells by loss
      of-function assays using either siRNA or randomized ribozyme library.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have employed
      bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified
      by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A
      to each of the four targets and found that the two closely related phytochemicals
      have differential binding properties to the selected cellular targets that can
      potentially instigate differential molecular effects. We validated these findings
      by undertaking parallel experiments on specific gene responses to either Wi-N or
      Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds
      strongly to the selected targets acts as a strong cytotoxic agent both for normal
      and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it
      showed milder cytotoxicity towards cancer cells and was safe for normal cells.
      The present molecular docking analyses and experimental evidence revealed
      important insights to the use of Wi-A and Wi-N for cancer treatment and
      development of new anti-cancer phytochemical cocktails.

PMID- 22973449
TI  - Dystrophin deficiency compromises force production of the extensor carpi ulnaris
      muscle in the canine model of Duchenne muscular dystrophy.
AB  - Loss of muscle force is a salient feature of Duchenne muscular dystrophy (DMD), a
      fatal disease caused by dystrophin deficiency. Assessment of force production
      from a single intact muscle has been considered as the gold standard for studying
      physiological consequences in murine models of DMD. Unfortunately, equivalent
      assays have not been established in dystrophic dogs. To fill the gap, we
      developed a novel in situ protocol to measure force generated by the extensor
      carpi ulnaris (ECU) muscle of a dog. We also determined the muscle length to
      fiber length ratio and the pennation angle of the ECU muscle. Muscle pathology
      and contractility were compared between normal and affected dogs. Absence of
      dystrophin resulted in marked histological damage in the ECU muscle of affected
      dogs. Central nucleation was significantly increased and myofiber size
      distribution was altered in the dystrophic ECU muscle. Muscle weight and
      physiological cross sectional area (PCSA) showed a trend of reduction in affected
      dogs although the difference did not reach statistical significance. Force
      measurement revealed a significant decrease of absolute force, and the PCSA or
      muscle weight normalized specific forces. To further characterize the
      physiological defect in affected dog muscle, we conducted eccentric contraction.
      Dystrophin-null dogs showed a significantly greater force loss following
      eccentric contraction damage. To our knowledge, this is the first convincing
      demonstration of force deficit in a single intact muscle in the canine DMD model.
      The method described here will be of great value to study physiological outcomes
      following innovative gene and/or cell therapies.

PMID- 22973448
TI  - Homodimerization of amyloid precursor protein at the plasma membrane: a homoFRET
      study by time-resolved fluorescence anisotropy imaging.
AB  - Classical FRET (Forster Resonance Energy Transfer) using two fluorescent labels
      (one for the donor and another one for the acceptor) is not efficient for
      studying the homodimerization of a protein as only half of the homodimers formed
      can be identified by this technique. We thus resorted to homoFRET detected by
      time-resolved Fluorescence Anisotropy IMaging (tr-FAIM). To specifically image
      the plasma membrane of living cells, an original combination of tr-FAIM and Total
      Internal Reflection Fluorescence Lifetime Imaging Microscope (TIRFLIM) was
      implemented. The correcting factor accounting for the depolarization due to the
      high numerical aperture (NA) objective, mandatory for TIRF microscopy, was
      quantified on fluorescein solutions and on HEK293 cells expressing enhanced Green
      Fluorescence Protein (eGFP). Homodimerization of Amyloid Precursor Protein (APP),
      a key mechanism in the etiology of Alzheimer's disease, was measured on this
      original set-up. We showed, both in epifluorescence and under TIRF excitation,
      different energy transfer rates associated with the homodimerization of wild type
      APP-eGFP or of a mutated APP-eGFP, which forms constitutive dimers. This original
      set-up thus offers promising prospects for future studies of protein
      homodimerization in living cells in control and pathological conditions.

PMID- 22973450
TI  - Protein clusters on the T cell surface may suppress spurious early signaling
      events.
AB  - T cells play an important role in the adaptive immune system, quickly activating
      effector functions in response to small numbers of antigenic peptides but rarely
      activating in response to constant interaction with most endogenous peptides.
      Emerging experimental evidence suggests that key membrane-bound signaling
      proteins such as the T cell receptor and the adaptor protein Lat are spatially
      organized into small clusters on the T cell membrane. We use spatially resolved,
      stochastic computer simulations to study how the inhomogeneous distribution of
      molecules affects the portion of the T cell signaling network in which the kinase
      ZAP-70, originating in T cell receptor clusters, phosphorylates Lat. To gain
      insight into the effects of protein clustering, we compare the signaling response
      from membranes with clustered proteins to the signaling response from membranes
      with homogeneously distributed proteins. Given a fixed amount of ZAP-70 (a proxy
      for degree of TCR stimulation) that must diffuse into contact with Lat molecules,
      the spatially homogeneous system responds faster and results in higher levels of
      phosphorylated Lat. Analysis of the spatial distribution of proteins demonstrates
      that, in the homogeneous system, nearest ZAP-70 and Lat proteins are closer on
      average and fewer Lat molecules share the same closest ZAP-70 molecule, leading
      to the faster response time. The results presented here suggest that spatial
      clustering of proteins on the T cell membrane may suppress the propagation of
      signal from ZAP-70 to Lat, thus providing a regulatory mechanism by which T cells
      suppress transient, spurious signals induced by stimulation of T cell receptors
      by endogenous peptides. Because this suppression of spurious signals may occur at
      a cost to sensitivity, we discuss recent experimental results suggesting other
      potential mechanisms by which ZAP-70 and Lat may interact to initiate T cell
      activation.

PMID- 22973451
TI  - Intermediate monocytes but not TIE2-expressing monocytes are a sensitive
      diagnostic indicator for colorectal cancer.
AB  - We have conducted the first study to determine the diagnostic potential of the
      CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of
      CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs) in cancer. These monocyte
      populations were investigated by flow cytometry in healthy volunteers (N = 32)
      and in colorectal carcinoma patients with localized (N = 24) or metastatic (N =
      37) disease. We further determined blood levels of cytokines associated with
      monocyte regulation. The results revealed the intermediate monocyte subset to be
      significantly elevated in colorectal cancer patients and to show the highest
      frequencies in localized disease. Multivariate regression analysis identified
      intermediate monocytes as a significant independent variable in cancer
      prediction. With a cut-off value at 0.37% (intermediate monocytes of total
      leukocytes) the diagnostic sensitivity and specificity ranged at 69% and 81%,
      respectively. In contrast, TEM levels were elevated in localized cancer but did
      not differ significantly between groups and none of the cytokines correlated with
      monocyte subpopulations. Of interest, in vitro analyses supported the observation
      that intermediate monocytes were more potently induced by primary as opposed to
      metastatic cancer cells which may relate to the immunosuppressive milieu
      established in the advanced stage of metastatic disease. In conclusion,
      intermediate monocytes as compared to TIE2-expressing monocytes are a more
      sensitive diagnostic indicator of colorectal cancer.

PMID- 22973452
TI  - Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell
      lymphoma.
AB  - BACKGROUND: Although several therapeutic options have become available for
      patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative.
      Recent studies have demonstrated that CTCL cells overexpress the CC chemokine
      receptor 4 (CCR4). METHODOLOGY/PRINCIPAL FINDINGS: In this study, a xenograft
      model of CTCL was established and a recombinant adeno-associated viral serotype 8
      (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc
      fusion (scFvFc or "minibody") of anti-CCR4 monoclonal antibody (mAb) h1567 was
      evaluated for curative treatment. Human CCR4+ tumor-bearing mice treated once
      with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567)
      minibody showed anti-tumor activity in vivo and increased survival. The AAV8
      h1567 minibody notably increased the number of tumor-infiltrating Ly-6G+
      FcgammaRIIIa(CD16A)+ murine neutrophils in the tumor xenografts over that of AAV8
      control minibody treated mice. Furthermore, in CCR4+ tumor-bearing mice co
      treated with AAV8-h1567 minibody and infused with human peripheral blood
      mononuclear cells (PBMCs), marked tumor infiltration of human CD16A+ CD56+ NK
      cells was observed. The h1567 minibody also induced in vitro ADCC activity
      through both mouse neutrophils and human NK cells. CONCLUSIONS/SIGNIFICANCE:
      Overall, our data demonstrate that the in vivo anti-tumor activity of h1567
      minibody is mediated, at least in part, through CD16A+ immune effector cell ADCC
      mechanisms. These data further demonstrate the utility of the AAV-minibody gene
      transfer system in the rapid evaluation of candidate anti-tumor mAbs and the
      potency of h1567 as a potential novel therapy for CTCL.

PMID- 22973453
TI  - Comprehensive binary interaction mapping of SH2 domains via fluorescence
      polarization reveals novel functional diversification of ErbB receptors.
AB  - First-generation interaction maps of Src homology 2 (SH2) domains with receptor
      tyrosine kinase (RTK) phosphosites have previously been generated using protein
      microarray (PM) technologies. Here, we developed a large-scale fluorescence
      polarization (FP) methodology that was able to characterize interactions between
      SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity
      than was previously achieved with PMs. We used the FP assay to query the
      interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor
      intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine
      binding (PTB) domains. From 358,944 polarization measurements, the affinities for
      1,405 unique biological interactions were determined, 83% of which are novel. In
      contrast to data from previous reports, our analyses suggested that ErbB2 was not
      more promiscuous than the other ErbB receptors. Our results showed that each
      receptor displays unique preferences in the affinity and location of recruited
      SH2 domains that may contribute to differences in downstream signaling potential.
      ErbB1 was enriched versus the other receptors for recruitment of domains from RAS
      GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and
      phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor
      family member, was predictably enriched for recruitment of domains from
      phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of
      domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but
      depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many
      novel interactions were also observed with phosphopeptides corresponding to ErbB
      receptor tyrosines not previously reported to be phosphorylated by mass
      spectrometry, suggesting the existence of many biologically relevant RTK sites
      that may be phosphorylated but below the detection threshold of standard mass
      spectrometry procedures. This dataset represents a rich source of testable
      hypotheses regarding the biological mechanisms of ErbB receptors.

PMID- 22973454
TI  - The reactivity, distribution and abundance of Non-astrocytic Inner Retinal Glial
      (NIRG) cells are regulated by microglia, acute damage, and IGF1.
AB  - Recent studies have described a novel type of glial cell that is scattered across
      the inner layers of the avian retina and possibly the retinas of primates. These
      cells have been termed Non-astrocytic Inner Retinal Glial (NIRG) cells. These
      cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate,
      migrate distally into the retina, and become reactive. These changes in glial
      activity correlate with increased susceptibility of retinal neurons and Muller
      glia to excitotoxic damage. The purpose of this study was to further study the
      NIRG cells in retinas treated with IGF1 or acute damage. In response to IGF1, the
      reactivity, proliferation and migration of NIRG cells persists through 3 days
      after treatment. At 7 days after treatment, the numbers and distribution of NIRG
      cells returns to normal, suggesting that homeostatic mechanisms are in place
      within the retina to maintain the numbers and distribution of these glial cells.
      By comparison, IGF1-induced microglial reactivity persists for at least 7 days
      after treatment. In damaged retinas, we find a transient accumulation of NIRG
      cells, which parallels the accumulation of reactive microglia, suggesting that
      the reactivity of NIRG cells and microglia are linked. When the microglia are
      selectively ablated by the combination of interleukin 6 and clodronate-liposomes,
      the NIRG cells down-regulate transitin and perish within the following week,
      suggesting that the survival and phenotype of NIRG cells are somehow linked to
      the microglia. We conclude that the abundance, reactivity and retinal
      distribution of NIRG cells can be dynamic, are regulated by homoestatic
      mechanisms and are tethered to the microglia.

PMID- 22973455
TI  - Oral administration of the pimelic diphenylamide HDAC inhibitor HDACi 4b is
      unsuitable for chronic inhibition of HDAC activity in the CNS in vivo.
AB  - Histone deacetylase (HDAC) inhibitors have received considerable attention as
      potential therapeutics for a variety of cancers and neurological disorders.
      Recent publications on a class of pimelic diphenylamide HDAC inhibitors have
      highlighted their promise in the treatment of the neurodegenerative diseases
      Friedreich's ataxia and Huntington's disease, based on efficacy in cell and mouse
      models. These studies' authors have proposed that the unique action of these
      compounds compared to hydroxamic acid-based HDAC inhibitors results from their
      unusual slow-on/slow-off kinetics of binding, preferentially to HDAC3, resulting
      in a distinctive pharmacological profile and reduced toxicity. Here, we evaluate
      the HDAC subtype selectivity, cellular activity, absorption, distribution,
      metabolism and excretion (ADME) properties, as well as the central
      pharmacodynamic profile of one such compound, HDACi 4b, previously described to
      show efficacy in vivo in the R6/2 mouse model of Huntington's disease. Based on
      our data reported here, we conclude that while the in vitro selectivity and
      binding mode are largely in agreement with previous reports, the physicochemical
      properties, metabolic and p-glycoprotein (Pgp) substrate liability of HDACi 4b
      render this compound suboptimal to investigate central Class I HDAC inhibition in
      vivo in mouse per oral administration. A drug administration regimen using HDACi
      4b dissolved in drinking water was used in the previous proof of concept study,
      casting doubt on the validation of CNS HDAC3 inhibition as a target for the
      treatment of Huntington's disease. We highlight physicochemical stability and
      metabolic issues with 4b that are likely intrinsic liabilities of the benzamide
      chemotype in general.

PMID- 22973456
TI  - Chemical chaperones improve protein secretion and rescue mutant factor VIII in
      mice with hemophilia A.
AB  - Inefficient intracellular protein trafficking is a critical issue in the
      pathogenesis of a variety of diseases and in recombinant protein production. Here
      we investigated the trafficking of factor VIII (FVIII), which is affected in the
      coagulation disorder hemophilia A. We hypothesized that chemical chaperones may
      be useful to enhance folding and processing of FVIII in recombinant protein
      production, and as a therapeutic approach in patients with impaired FVIII
      secretion. A tagged B-domain-deleted version of human FVIII was expressed in
      cultured Chinese Hamster Ovary cells to mimic the industrial production of this
      important protein. Of several chemical chaperones tested, the addition of betaine
      resulted in increased secretion of FVIII, by increasing solubility of
      intracellular FVIII aggregates and improving transport from endoplasmic reticulum
      to Golgi. Similar results were obtained in experiments monitoring recombinant
      full-length FVIII. Oral betaine administration also increased FVIII and factor IX
      (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer.
      Moreover, in vitro and in vivo applications of betaine were also able to rescue a
      trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical
      chaperones such as betaine might represent a useful treatment concept for
      hemophilia and other diseases caused by deficient intracellular protein
      trafficking.

PMID- 22973458
TI  - Origin of the words denoting some of the most ancient old world pulse crops and
      their diversity in modern European languages.
AB  - This preliminary research was aimed at finding the roots in various Eurasian
      proto-languages directly related to pulses and giving the words denoting the same
      in modern European languages. Six Proto-Indo-European roots were indentified,
      namely arnk(')- ('a leguminous plant'), *bhabh- ('field bean'), *[Formula: see
      text] ('a kernel of leguminous plant', 'pea'), ghArs- ('a leguminous plant'),
      *kek- ('pea') and *lent- ('lentil'). No Proto-Uralic root was attested save
      hypothetically *kaca ('pea'), while there were two Proto-Altaic roots, *bukrV
      ('pea') and *[Formula: see text] ('lentil'). The Proto-Caucasianx root *[Formula:
      see text] denoted pea, while another one, *howl(a) ('bean', 'lentil') and the
      Proto-Basque root *ilha-r ('pea', 'bean', 'vetch') could have a common Proto-Sino
      Caucasian ancestor, *hVwlV ('bean') within the hypothetic Dene-Caucasian language
      superfamily. The Modern Maltese preserved the memory of two Proto-Semitic roots,
      *'adas- ('lentil') and *pul- ('field bean'). The presented results prove that the
      most ancient Eurasian pulse crops were well-known and extensively cultivated by
      the ancestors of all modern European nations. The attested lexicological
      continuum witnesses the existence of a millennia-long links between the peoples
      of Eurasia to their mutual benefit. This research is meant to encourage
      interdisciplinary concerted actions between plant scientists dealing with crop
      evolution and biodiversity, archaeobotanists and language historians.

PMID- 22973457
TI  - Biofilms of a Bacillus subtilis hospital isolate protect Staphylococcus aureus
      from biocide action.
AB  - The development of a biofilm constitutes a survival strategy by providing
      bacteria a protective environment safe from stresses such as microbicide action
      and can thus lead to important health-care problems. In this study, biofilm
      resistance of a Bacillus subtilis strain (called hereafter ND(medical)) recently
      isolated from endoscope washer-disinfectors to peracetic acid was investigated
      and its ability to protect the pathogen Staphylococcus aureus in mixed biofilms
      was evaluated. Biocide action within Bacillus subtilis biofilms was visualised in
      real time using a non-invasive 4D confocal imaging method. The resistance of
      single species and mixed biofilms to peracetic acid was quantified using standard
      plate counting methods and their architecture was explored using confocal imaging
      and electronic microscopy. The results showed that the ND(medical) strain
      demonstrates the ability to make very large amount of biofilm together with hyper
      resistance to the concentration of PAA used in many formulations (3500 ppm).
      Evidences strongly suggest that the enhanced resistance of the ND(medical) strain
      was related to the specific three-dimensional structure of the biofilm and the
      large amount of the extracellular matrix produced which can hinder the
      penetration of peracetic acid. When grown in mixed biofilm with Staphylococcus
      aureus, the ND(medical) strain demonstrated the ability to protect the pathogen
      from PAA action, thus enabling its persistence in the environment. This work
      points out the ability of bacteria to adapt to an extremely hostile environment,
      and the necessity of considering multi-organism ecosystems instead of single
      species model to decipher the mechanisms of biofilm resistance to antimicrobials
      agents.

PMID- 22973459
TI  - Antigen-bound and free beta-amyloid autoantibodies in serum of healthy adults.
AB  - Physiological beta-amyloid autoantibodies (Abeta-autoantibodies) are currently
      investigated as potential diagnostic and therapeutic tools for Alzheimer's
      disease (AD). In previous studies, their determination in serum and cerebrospinal
      fluid (CSF) using indirect ELISA has provided controversial results, which may be
      due to the presence of preformed Abeta antigen-antibody immune complexes. Based
      on the epitope specificity of the Abeta-autoantibodies, recently elucidated in
      our laboratory, we developed (a) a sandwich ELISA for the determination of
      circulating Abeta-IgG immune complexes and (b) an indirect ELISA for the
      determination of free Abeta-autoantibodies. This methodology was applied to the
      analysis of serum samples from healthy individuals within the age range of 18 to
      89 years. Neuropsychological examination of the participants in this study
      indicated non-pathological, age-related cognitive decline, revealed especially by
      tests of visual memory and executive function, as well as speed-related tasks.
      The ELISA serum determinations showed significantly higher levels of Abeta-IgG
      immune complexes compared to free Abeta-autoantibodies, while no correlation with
      age or cognitive performance of the participants was found.

PMID- 22973460
TI  - Edge effects on foliar stable isotope values in a Madagascan tropical dry forest.
AB  - Edge effects represent an inevitable and important consequence of habitat loss
      and fragmentation. These effects include changes in microclimate, solar
      radiation, or temperature. Such abiotic effects can, in turn, impact biotic
      factors. They can have a substantial impact on species, communities, and
      ecosystems. Here we examine clinal variations in stable carbon and nitrogen
      isotope values for trees along an edge-interior gradient in the dry deciduous
      forest at Ankarafantsika National Park. We predicted that soil respiration and
      differences in solar irradiance would result in stratified delta13C values where
      leaves collected close to the forest floor would have lower delta13C values than
      those growing higher up in the canopy. We also anticipated that plants growing at
      the savannah-forest boundary would have higher delta13C and delta15N values than
      plants growing in the forest interior. As expected, we detected a small but
      significant canopy effect. Leaves growing below 2 m from the forest floor exhibit
      delta13C values that are, on average, 1.10/00 lower than those growing above this
      threshold. We did not, however, find any relationship between foliar delta13C and
      distance from the edge. Unpredictably, we detected a striking positive
      relationship between foliar delta15N values and increasing distance into the
      forest interior. Variability in physiology among species, anthropogenic
      influence, organic input, and rooting depth cannot adequately explain this trend.
      Instead, this unexpected relationship most likely reflects decreasing nutrient or
      water availability, or a shift in N-sources with increasing distance from the
      savannah. Unlike most forest communities, the trees at Ampijoroa are growing in
      nutrient-limited sands. In addition to being nutrient poor, these well-drained
      soils likely decrease the amount of soil water available to forest vegetation.
      Continued research on plant responses to edge effects will improve our
      understanding of the conservation biology of forest ecosystems in Madagascar.

PMID- 22973461
TI  - Association of N-terminal pro-brain natriuretic peptide with cognitive function
      and depression in elderly people with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus is associated with risk of congestive heart
      failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to
      poor cognition and depression. The ventricular N-terminal pro-brain natriuretic
      peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for
      cognitive impairment and/or depression. This was tested in the Edinburgh Type 2
      Diabetes Study (ET2DS). METHODOLOGY AND PRINCIPAL FINDINGS: Cross-sectional
      analysis of 1066 men and women aged 60-75 with type 2 diabetes. Results from
      seven neuropsychological tests were combined in a standardised general cognitive
      ability factor, 'g'. A vocabulary-based test estimated pre-morbid cognitive
      ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible
      depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly
      associated with lower 'g' and higher depression scores (beta -0.09, 95% CI -0.13
      to -0.03, p = 0.004 and beta 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively).
      Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were
      more likely to have reduced cognitive ability (within the lowest tertile of 'g')
      and 'possible' depression (HADS depression >=8) (OR 1.80; 95% CI: 1.20, 2.70; p =
      0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations
      persisted when pre-morbid ability was adjusted for, but as expected were no
      longer statistically significant following the adjustment for diabetes-related
      and vascular co-variates (beta -0.02, 95% CI -0.07 to 0.03, p>0.05 for 'g'; beta
      0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores). CONCLUSION: Raised
      plasma NT-proBNP was weakly but statistically significantly associated with
      poorer cognitive function and depression. The prospective phases of the ET2DS
      will help determine whether or not NT-proBNP can be considered a risk marker for
      subsequent cognitive impairment and incident depression and whether it provides
      additional information over and above traditional risk factors for these
      conditions.

PMID- 22973462
TI  - A single bout of exercise improves motor memory.
AB  - Regular physical activity has a positive impact on cognition and brain function.
      Here we investigated if a single bout of exercise can improve motor memory and
      motor skill learning. We also explored if the timing of the exercise bout in
      relation to the timing of practice has any impact on the acquisition and
      retention of a motor skill. Forty-eight young subjects were randomly allocated
      into three groups, which practiced a visuomotor accuracy-tracking task either
      before or after a bout of intense cycling or after rest. Motor skill acquisition
      was assessed during practice and retention was measured 1 hour, 24 hours and 7
      days after practice. Differences among groups in the rate of motor skill
      acquisition were not significant. In contrast, both exercise groups showed a
      significantly better retention of the motor skill 24 hours and 7 days after
      practice. Furthermore, compared to the subjects that exercised before practice,
      the subjects that exercised after practice showed a better retention of the motor
      skill 7 days after practice. These findings indicate that one bout of intense
      exercise performed immediately before or after practicing a motor task is
      sufficient to improve the long-term retention of a motor skill. The positive
      effects of acute exercise on motor memory are maximized when exercise is
      performed immediately after practice, during the early stages of memory
      consolidation. Thus, the timing of exercise in relation to practice is possibly
      an important factor regulating the effects of acute exercise on long-term motor
      memory.

PMID- 22973463
TI  - An approach to localizing corneal pain representation in human primary
      somatosensory cortex.
AB  - The cornea has been a focus of animal electrophysiological research for decades,
      but little is known regarding its cortical representation in the human brain.
      This study attempts to localize the somatotopic representation of the cornea to
      painful stimuli in human primary somatosensory cortex using functional magnetic
      resonance imaging (fMRI). In this case study, a subject was imaged at 3T while
      bright light was presented in a block-design, which either produced pain and
      blinking (during photophobia) or blinking alone (after recovery from
      photophobia). Pain and blinking produced precisely localized activations in
      primary somatosensory cortex and primary motor cortex. These results indicate
      that noxious stimulation of the cornea can produce somatotopic activation in
      primary somatosensory cortex. This finding opens future avenues of research to
      evaluate the relationship between corneal pain and central brain mechanisms
      relating to the development of chronic pain conditions, such as dry eye-like
      symptoms.

PMID- 22973464
TI  - Cardiac subsarcolemmal and interfibrillar mitochondria display distinct
      responsiveness to protection by diazoxide.
AB  - OBJECTIVE: Cardiac subsarcolemmal (SSM) and interfibrillar (IFM) mitochondrial
      subpopulations possess distinct biochemical properties and differ with respect to
      their protein and lipid compositions, capacities for respiration and protein
      synthesis, and sensitivity to metabolic challenge, yet their responsiveness to
      mitochondrially active cardioprotective therapeutics has not been characterized.
      This study assessed the differential responsiveness of the two mitochondrial
      subpopulations to diazoxide, a cardioprotective agent targeting mitochondria.
      METHODS: Mitochondrial subpopulations were freshly isolated from rat ventricles
      and their morphologies assessed by electron microscopy and enzymatic activities
      determined using standard biochemical protocols with a plate reader. Oxidative
      phosphorylation was assessed from State 3 respiration using succinate as a
      substrate. Calcium dynamics and the status of Ca2+-dependent mitochondrial
      permeability transition (MPT) pore and mitochondrial membrane potential were
      assessed using standard Ca2+ and TPP+ ion-selective electrodes. RESULTS: Compared
      to IFM, isolated SSM exhibited a higher sensitivity to Ca2+ overload-mediated
      inhibition of adenosine triphosphate (ATP) synthesis with decreased ATP
      production (from 375+/-25 to 83+/-15 nmol ATP/min/mg protein in SSM, and from
      875+/-39 to 583+/-45 nmol ATP/min/mg protein in IFM). In addition, SSM exhibited
      reduced Ca2+-accumulating capacity as compared to IFM (230+/-13 vs. 450+/-46 nmol
      Ca2+/mg protein in SSM and IFM, respectively), suggestive of increased Ca2+
      sensitivity of MPT pore opening. Despite enhanced susceptibility to stress, SSM
      were more responsive to the protective effect of diazoxide (100 MUM) against Ca2+
      overload-mediated inhibition of ATP synthesis (67% vs. 2% in SSM and IFM,
      respectively). CONCLUSION: These results provide evidence for the distinct
      sensitivity of cardiac SSM and IFM toward Ca2+-dependent metabolic stress and the
      protective effect of diazoxide on mitochondrial energetics.

PMID- 22973465
TI  - IVTA as adjunctive treatment to PRP and MPC for PDR and macular edema: a meta
      analysis.
AB  - BACKGROUND: To quantify the effect of a combination treatment of intravitreal
      triamcinolone acetonide (IVTA) injection, panretinal photocoagulation (PRP), and
      macular photocoagulation (MPC) in patients with proliferative diabetic
      retinopathy (PDR) and diabetic macular edema (DME). METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a meta-analysis and searched for reports concerning IVTA
      injection combined with PRP for the treatment of PDR and DME using Medline,
      EMbase, Web of Science, the Cochrane Library, and Google according to Cochrane
      evaluation guidelines. The quality of the reports was evaluated using the Jadad
      score. Only four studies were ultimately included in this meta-analysis and the
      fixed-effects model was used. Treatment with IVTA injection combined with PRP and
      MPC significantly improved BCVA (p<0.001) from one to six months, compared with
      PRP and MPC alone. There was a statistically significant mean difference in
      central macular thickness (CMT), at the one-month follow-up (p<0.001). No
      evidence of publication bias was present. There was a low level of heterogeneity
      in this group of studies. CONCLUSIONS/SIGNIFICANCE: This meta-analysis indicates
      that IVTA injection combined with PRP and MPC results in an improvement of BCVA,
      and CMT reduction in patients with PDR and DME.

PMID- 22973466
TI  - Molecular control of TiO2-NPs toxicity formation at predicted environmental
      relevant concentrations by Mn-SODs proteins.
AB  - With growing concerns of the safety of nanotechnology, the in vivo toxicity of
      nanoparticles (NPs) at environmental relevant concentrations has drawn increasing
      attentions. We investigated the possible molecular mechanisms of titanium
      nanoparticles (Ti-NPs) in the induction of toxicity at predicted environmental
      relevant concentrations. In nematodes, small sizes (4 nm and 10 nm) of TiO2-NPs
      induced more severe toxicities than large sizes (60 nm and 90 nm) of TiO2-NPs on
      animals using lethality, growth, reproduction, locomotion behavior, intestinal
      autofluorescence, and reactive oxygen species (ROS) production as endpoints.
      Locomotion behaviors could be significantly decreased by exposure to 4-nm and 10
      nm TiO2-NPs at concentration of 1 ng/L in nematodes. Among genes required for the
      control of oxidative stress, only the expression patterns of sod-2 and sod-3
      genes encoding Mn-SODs in animals exposed to small sizes TiO2-NPs were
      significantly different from those in animals exposed to large sizes of TiO2-NPs.
      sod-2 and sod-3 gene expressions were closely correlated with lethality, growth,
      reproduction, locomotion behavior, intestinal autofluorescence, and ROS
      production in TiO2-NPs-exposed animals. Ectopically expression of human and
      nematode Mn-SODs genes effectively prevented the induction of ROS production and
      the development of toxicity of TiO2-NPs. Therefore, the altered expression
      patterns of Mn-SODs may explain the toxicity formation for different sizes of
      TiO2-NPs at predicted environmental relevant concentrations. In addition, we
      demonstrated here a strategy to investigate the toxicological effects of exposure
      to NPs upon humans by generating transgenic strains in nematodes for specific
      human genes.

PMID- 22973467
TI  - PGC-1alpha induction in pulmonary arterial hypertension.
AB  - Idiopathic Pulmonary arterial hypertension (IPAH) is characterized by the
      obstructive remodelling of pulmonary arteries, and a progressive elevation in
      pulmonary arterial pressure (PAP) with subsequent right-sided heart failure and
      dead. Hypoxia induces the expression of peroxisome proliferator activated
      receptor gamma coactivator-1alpha (PGC-1alpha) which regulates oxidative
      metabolism and mitochondrial biogenesis. We have analysed the expression of PGC
      1alpha, cytochrome C (CYTC), superoxide dismutase (SOD), the total antioxidant
      status (TAS) and the activity of glutathione peroxidase (GPX) in blood samples of
      IPAH patients. Expression of PGC-1alpha was detected in IPAH patients but not in
      healthy volunteers. The mRNA levels of SOD were lower in IPAH patients compared
      to controls (3.93 +/- 0.89 fold change). TAS and GPX activity were lower too in
      patients compared to healthy donors, (0.13 +/- 0.027 versus 0.484 +/- 0.048 mM
      and 56.034 +/- 10.37 versus 165.46 +/- 11.38 nmol/min/mL, resp.). We found a
      negative correlation between expression levels of PGC-1alpha and age, PAP and
      PVR, as well as a positive correlation with CI, PaO(2), mRNA levels of CYTC and
      SOD, TAS and GPX activity. These results taken together are indicative of the
      possible role of PGC-1alpha as a potential biomarker of the progression of IPAH.

PMID- 22973468
TI  - Redox status is critical for stemness in skin equivalents.
AB  - The skin is constantly exposed to environmental oxidative stress. Skin equivalent
      (SE) models are three-dimensional systems in which cell-cell or cell-matrix
      interactions can be investigated. In this study, the effects of vitamin C or
      plant extracts with high antioxidant activities were tested. There was no
      significant difference in the epidermal thickness, but the basal cells became
      cuboidal when vitamin C or plant extracts were supplemented. Furthermore,
      immunohistochemical staining showed linear and intense staining of alpha6 and
      beta1 integrin along the basement membrane in vitamin C or plant extract treated
      models. The p63 and PCNA were also stained. Results showed that the number of p63
      and PCNA positive cells was higher in the vitamin C or plant extract treated
      models than in the control SEs. Although the relationship between oxidative
      stress and stem cells is not known, our results suggest that redox status affects
      the stemness and the proliferative potential of epidermal basal cells by
      modulating microenvironment to epidermal basal stem cells.

PMID- 22973469
TI  - Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and
      HCV.
AB  - BACKGROUND AND OBJECTIVES: Developed in 1991, nucleic acid sequence-based
      amplification (NASBA) has been introduced as a rapid molecular diagnostic
      technique, where it has been shown to give quicker results than PCR, and it can
      also be more sensitive. This paper describes the development of a molecular
      beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in
      plasma samples. MATERIALS AND METHODS: A well-conserved region in the HIV-1 pol
      gene and 5'-NCR of HCV genome were used for primers and molecular beacon design.
      The performance features of HCV/HIV-1 multiplex NASBA assay including analytical
      sensitivity and specificity, clinical sensitivity and clinical specificity were
      evaluated. RESULTS: The analysis of scalar concentrations of the samples
      indicated that the limit of quantification of the assay was <1000 copies/ml for
      HIV-1 and <500 copies/ml for HCV with 95% confidence interval. Multiplex NASBA
      assay showed a 98% sensitivity and 100% specificity. The analytical specificity
      study with BLAST software demonstrated that the primers do not attach to any
      other sequences except for that of HIV-1 or HCV. The primers and molecular beacon
      probes detected all HCV genotypes and all major variants of HIV-1. CONCLUSION:
      This method may represent a relatively inexpensive isothermal method for
      detection of HIV-1/HCV co-infection in monitoring of patients.

PMID- 22973470
TI  - Cloning of fimH and fliC and expression of the fusion protein FimH/FliC from
      Uropathogenic Escherichia coli (UPEC) isolated in Iran.
AB  - BACKGROUND AND OBJECTIVES: Urinary tract infection (UTI) is one of the most
      common infections in the world. The majority of UTIs are caused by Uropathogenic
      Escherichia coli (UPEC) strains. FimH and FliC are the most important virulence
      factors of UPEC. To date, any ideal vaccine against UTI has not been approved for
      human use and we need to test new targets to develop an ideal vaccine against
      UTI. In this study, we constructed fusion fimH/fliC of UPEC as a novel vaccine
      candidate against UTI. MATERIAL AND METHODS: PCR amplification of fimH and fliC
      genes of the UPEC isolates was performed by specific primers designed for this
      purpose. Construction of fimH/fliC hybrid gene was performed by overlap PCR. The
      fimH, fliC and fimH/fliC were cloned in pET28a vector. The confirmation of
      expression of the proteins was done by SDS-PAGE and Western blot. RESULTS: The
      fliC and fimH genes were amplified in all of the UPEC isolates tested. The fimH
      showed significant homology with the sequences in GenBank. We generated a fusion
      consisting of the fimH linked to the N-terminal end of fliC. Sequencing of the
      fusion fimH/fliC showed that fusion was constructed correctly. SDS-PAGE and
      western blot confirmed the expression of the proteins in optimized condition.
      CONCLUSION: Urinary tract infection is a huge burden on healthcare system in many
      countries. UPEC is isolated in around 80% of UTI cases. Antibiotic therapy
      resulted in the emergence of antibiotic resistance in UPEC strains. This is the
      major cause for an increasing requirement for a vaccine to prevent UTI. This work
      describes for the first time the construction of a novel fusion protein from
      Iranian UPEC isolates. Further immunological studies are required for evaluation
      of this protein as a novel and safe vaccine candidate against UTI caused by UPEC.

PMID- 22973471
TI  - Characterization of Shiga toxin-producing Escherichia coli (STEC) in feces of
      healthy and diarrheic calves in Urmia region, Iran.
AB  - BACKGROUND AND OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) have
      emerged as human pathogens and contamination of foods of animal origin has been a
      major public health concern. The aim of the present study was to determine the
      dissemination of STEC in healthy and diarrheic calves in Urmia region which is
      located in West Azerbaijan province, Iran. MATERIALS AND METHODS: In the current
      study, a total of 124 Escherichia coli isolates from clinically healthy (n = 73)
      and diarrheic calves (51) belonging to 6 different farms located in West
      Azerbaijan province, Iran, were screened by the polymerase chain reaction (PCR)
      assay for the presence of virulence genes characteristic for STEC, that is, Shiga
      toxin producing gene(s) (stx1, stx2), intimin (eaeA) and enterohemolysin (hlyA).
      RESULTS: STEC isolates were recovered from 21.92% (16/73) in healthy calves, and
      19.6% (10/51) in diarrheic calves. Overall, PCR results showed that 6 (23.1%)
      isolates carried stx1 gene, 7 (26.92%) possessed stx2 gene while 13 isolates
      (50%) gave positive amplicon both for stx1 and stx2 genes. All stx positive
      isolates were assayed further to detect eaeA and hlyA sequences. Seven out of the
      26 (26.92%) Shiga toxin gene positive isolates were positive for the eaeA gene,
      and 15 (57.69%) were positive for the hlyA gene. Both virulence genes (eaeA and
      hlyA) in the same isolate were observed in 5 (19.23%) of the stx(+) isolates. In
      total, diverse virulence gene profiles were detected, from which isolates with
      the genetic profile stx1 stx2 hlyA was the most prevalent. In addition, eaeA gene
      was more evident in isolates from diarrheic calves than in healthy calves.
      CONCLUSION: There was no significant difference in detecting STEC isolates
      between healthy and diarrheic calves. It seems that calves to be the reservoir of
      STEC within the herds and calf management may represent specific control points
      for reducing STEC spread within dairy units.

PMID- 22973472
TI  - Development of a Reverse Line Blot Hybridization method for Detection of some
      Streptococcal/Lactococcal Species, the causative agents of Zoonotic
      Streptococosis/Lactococosis in farmed fish.
AB  - BACKGROUND AND OBJECTIVE: Streptococcosis/lactococcosis is the cause of high
      morbidity and mortality in aquaculture sector and to date a number of species of
      Streptococcus and Lactococcus genera including S. iniae, S. agalactiae, S.
      dysagalactiae, S. parauberis, S. feacalis, L. garvieae and L. lactis have been
      discriminated as the cause of disease in aquatic animals. Despite the use of
      diagnostic molecular methods for each of these bacterial species, no data is
      available on a suitable, rapid and simple simultaneous detection tool for these
      pathogens. This paper describes a simultaneous detection method which is PCR
      based on a reverse line blot (RLB) for rapid detection and differentiation of
      four species of genera of Streptococcus and Lactococcus genera consisting of S.
      iniae, S. agalactiae, S. parauberis and L. garvieae the most important agents of
      the disease in fish. MATERIALS AND METHODS: A reverse line blot (RLB) assay was
      developed for the simultaneously identification of four species of
      Streptococcus/lactococcusconsisting of S. iniae, S. parauberis, S. agalactiaeand
      Lactococcusgarvieae. The assay employs one set of primer pair for specific
      amplification of the 16S rRNA gene. These were designed based on the nucleotide
      sequences of 16S rRNA gene sharing a homology region with Streptococcus spp. and
      Lactococcus spp. DNA was extracted from the pure bacterial colonies and
      amplified. A membrane was prepared with specific oligonucleotide for each
      bacterial species. PCR products were then hybridized to a membrane. RESULTS AND
      CONCLUSION: The amplification resulted in PCR product of 241 bp in length. No
      cross-reactions were observed between any of the tested bacterial species, and
      mixed DNAs from these four bacterial species were correctly identified. This RLB
      method is a suitable technique for a simultaneous detection of these species of
      bacterial fish pathogens that are some of the main causes of
      streptococcal/lactococcal infections in both freshwater and marine aquatic
      animals, and so we recommend its use for integrated epidemiological monitoring of
      streptococcosis/lactococcis in aquaculture industry.

PMID- 22973473
TI  - Effect of xylitol on cariogenic and beneficial oral streptococci: a randomized,
      double-blind crossover trial.
AB  - BACKGROUND/PURPOSE: Although habitual consumption of xylitol reduces cariogenic
      streptococci levels, its effect on beneficial oral streptococci is less clear.
      The main aim of the study is to investigate the effect of short-term xylitol
      consumption on the oral beneficial streptococci level of saliva, Streptococcus
      sanguinis and S. mitis. MATERIAL AND METHODS: Twenty four volunteers with a
      median age of 23.7 years (range: 20-28) harboring Streptococcus mutans, S.
      sobrinus, S. sanguinis and S. mitis participated in the randomized, double-blind,
      cross-over study. The experimental chewing gum (1.5 g/pellet) contained 70%
      xylitol w/w while the control gum contained 63% sorbitol w/w. Saliva samples were
      collected before and after two three-week test periods with a four-week washout
      interval. Colony-forming units (CFU)/ml were enumerated for the estimation of S.
      mutans levels on Mitis Salivarius-Mutans valinomycin (MS-MUTV), S. sobrinus on
      Mitis Salivarius-Sobrinus (MS-SOB), S. sanguinis on Modified Medium 10-Sucrose
      (MM10-S) and S. mitis on Mitis Salivarius Agar with Tellurite (MSAT) media.
      RESULTS: The S. mutans and S. sobrinus counts of the saliva samples decreased
      significantly (p = 0.01 and p = 0.011, respectively) in the xylitol gum group but
      not in the sorbitol gum group. The salivary S. sanguinis and S. mitis counts did
      not decrease in both xylitol and sorbitol gum groups. CONCLUSIONS: Based on the
      findings of this study, xylitol consumption reduced S. mutans and S. sobrinus
      counts in saliva but appeared not to effect numbers of S. sanguinis and S. mitis
      in saliva. So, habitual consumption of xylitol reduces cariogenic streptococci
      levels without any effect on beneficial sterptococci for the oral cavity.

PMID- 22973474
TI  - Inducible clindamycin resistance in Staphylococcus aureus isolates recovered from
      Mashhad, Iran.
AB  - BACKGROUND AND OBJECTIVES: Staphylococcus aureus is an important agent in
      hospital and community-associated infections, causing high morbidity and
      mortality. Introduction of the new antimicrobial classes for this pathogen has
      been usually followed by the emergence of resistant strains through multiple
      mechanisms. For instance, resistance to clindamycin (CLI)can be constitutive or
      inducible. Inducible clindamycin resistance which may lead to treatment failure
      can simply be identified by performing D-test. The aim of this study was to
      determine the prevalence of inducible clindamycin resistance among Staphylococcus
      aureus isolates by D-test method. MATERIALS AND METHODS: This was a cross
      sectional study conducted on 211 non-duplicated S. aureus isolates in Imam Reza
      hospital of Mashhad during 2010. Susceptibility to oxacillin, cefoxitin,
      erythromycin and clindamycin was performed by agar disk diffusion method
      according to CLSI guidelines and D-shaped clindamycin susceptibility patterns
      where considered as D-test positive (D(+)). RESULTS: Of 211 S. aureus isolates,88
      (41.7%) were methicillin resistant. It was found that of 88 MRSA isolates, 78
      (88.6%) were erythromycin (ERY) resistant and 46 (52.3%) were CLI resistant. ERY
      and CLI resistance in MSSA strains was 22% and 10.6% respectively. Inducible
      clindamycin resistance was detected in 18 (20.5%) MRSA isolates. 47(53.4%) of
      MRSA isolates and 9 (7.3%) of MSSA showed constitutive MLS(B) phenotype.
      CONCLUSION: In conclusion, we found a high prevalence of inducible clindamycin
      resistance phenotype in our region. We recommend that whenever clindamycin is
      intended to be used for S. aureus infections, D-test should be performed to
      facilitate the appropriate treatment of patients.

PMID- 22973475
TI  - Comparison of Butyric acid concentrations in ordinary and probiotic yogurt
      samples in Iran.
AB  - BACKGROUND AND OBJECTIVES: Butyric acid has many applications in chemical, food
      and pharmaceutical industries. Applications of butyric acid are as an additive to
      food, flavorings, varnishes, perfumes, pharmaceuticals and disinfectants. Butyric
      acid concentrations have positive impact on the quality control of milk, yogurt
      and other probiotic dairy products. The present investigation was undertaken to
      determine and compare the concentrations of butyric acid (C4) in the ordinary and
      probiotic yogurt samples by GC method. MATERIALS AND METHODS: Probiotic yogurt
      samples were prepared under laboratory scale conditions using two different
      commercial starters ABY1 and 211, while ordinary yogurt samples lacked the
      probiotic starter cultures. All samples were analyzed in duplicate, for C4
      concentrations by gas chromatography after day 1, 2, 10 and 20 of production,
      during storage at 4 degrees C. The results were analyzed using ANOVA and Duncan
      test. RESULTS: The level of the mentioned fatty acid in ABY1 yogurt sample was
      significantly higher (0.2%) than in 211 samples (0.17%). These values were
      significantly lower in ordinary yogurt samples and only 0.07% was recorded in
      these samples on first day of storage which decreased gradually during storage.
      The level of reduction in the yogurt samples tested during different time
      intervals was not similar in all the examined samples, and some showed enhanced
      reduction than other samples. CONCLUSIONS: Compared to ordinary yogurt samples,
      probiotic yogurt samples used in study showed higher levels of butyric acid with
      increased shelf life.

PMID- 22973476
TI  - Drug resistance pattern of Pseudomonas aeruginosa strains isolated from cystic
      fibrosis patients at Isfahan AL Zahra hospital, Iran (2009-2010).
AB  - BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is an autosomal recessive genetic
      disease. Infections in these patients are mostly caused by three bacteria:
      Staphylococcus aureus, Haemophilus influenza and particularly Pseudomonas
      aeruginosa. Carbapenems including antibiotics are used to combat infections with
      Pseudomonas aeruginosa. In recent years, carbapenems resistant strains of P.
      aeruginosa isolated from clinical specimens are being reported. Decrease in drug
      penetration and production of metalobeta lactamase (MBLS) have been proposed as
      mechanisms of resistance. MATERIALS AND METHODS: In this descriptive study, the
      population under investigation was 27 patients suffering from CF in Alzahra
      hospital of Isfahan. Clinical specimens were taken by deep swabbing from throat
      and data from every patient was recorded in a questionnaire. The specimens were
      cultured and isolated organisms were identified as P. aeruginosa using standard
      tests. Kirby-Bauer disk diffusion method was used to determine the bacterial drug
      resistance pattern. Strains of P. aeruginosa were checked for production of MBLS
      using disk impregnated with IPM-EDTA and PCR targeting of bla(VIM). RESULTS:
      Among the 27 patients, 7 (26%) had P. aeruginosa infection. In total, 11 P.
      aeruginosa isolates were taken. All isolates were susceptible to imipenem,
      ticarcillin, ciprofloxacin and piperacillin. The lowest scale of susceptibility
      belonged to ceftazidime (72.2%) followed by tobramycin (45.4%). None of the
      strains were positive for the bla(VIM) gene. CONCLUSION: Isolates of P.
      aeruginosa from CF patients in Isfahan were susceptible to antibiotics during the
      study period.

PMID- 22973478
TI  - Infectious disease surveillance.

PMID- 22973477
TI  - Small Colony variants of Staphylococcus aureus isolated from a patient with
      infective endocarditis: a case report and review of the literature.
AB  - Staphylococcus aureus produces a particular morphological variant called small
      colony variant (SCV) which is responsible for persistent subclinical infections
      in predisposed individuals and is usually resistant to aminoglycosides and cell
      wall active antibiotics. Infections by SCV of S. aureus are an upcoming problem
      due to difficulty in laboratory diagnosis and resistance to antimicrobial
      chemotherapy. We here report a case of infective endocarditis caused by SCV of
      Staphylococcus aureus in a pediatric patient.

PMID- 22973479
TI  - Avicenna as the Forerunner of Preventive Medicine: On the Occasion of 1032(nd)
      Birth Anniversary of Avicenna (22 August 980).

PMID- 22973480
TI  - On the occasion of the world breastfeeding week: the promotion of breastfeeding
      in the I.R. Iran.

PMID- 22973481
TI  - Comparison of models for predicting outcomes in patients with coronary artery
      disease focusing on microsimulation.
AB  - BACKGROUND: Physicians have difficulty to subjectively estimate the
      cardiovascular risk of their patients. Using an estimate of global cardiovascular
      risk could be more relevant to guide decisions than using binary representation
      (presence or absence) of risk factors data. The main aim of the paper is to
      compare different models of predicting the progress of a coronary artery diseases
      (CAD) to help the decision making of physician. METHODS: There are different
      standard models for predicting risk factors such as models based on logistic
      regression model, Cox regression model, dynamic logistic regression model, and
      simulation models such as Markov model and microsimulation model. Each model has
      its own application which can or cannot use by physicians to make a decision on
      treatment of each patient. RESULTS: There are five main common models for
      predicting of outcomes, including models based on logistic regression model (for
      short-term outcomes), Cox regression model (for intermediate-term outcomes),
      dynamic logistic regression model, and simulation models such as Markov and
      microsimulation models (for long-term outcomes). The advantages and disadvantages
      of these models have been discussed and summarized. CONCLUSION: Given the complex
      medical decisions that physicians face in everyday practice, the multiple
      interrelated factors that play a role in choosing the optimal treatment, and the
      continuously accumulating new evidence on determinants of outcome and treatment
      options for CAD, physicians may potentially benefit from a clinical decision
      support system that accounts for all these considerations. The microsimulation
      model could provide cardiologists, researchers, and medical students a user
      friendly software, which can be used as an intelligent interventional simulator.

PMID- 22973482
TI  - Effects of cinnamon consumption on glycemic status, lipid profile and body
      composition in type 2 diabetic patients.
AB  - OBJECTIVE: Type 2 diabetes is the most common metabolic disorder worldwide.
      Traditional herbs and spices can be used to control blood glucose concentrations.
      The objective of this study was to evaluate the effects of the daily intake of
      three grams cinnamon over eight weeks on glycemic status, lipid profiles and body
      composition in type 2 diabetic patients. METHODS: A double blind, randomized,
      placebo controlled clinical trial was conducted on 44 patients with type 2
      diabetes. Participants were randomly assigned to take either a three g/day
      cinnamon supplement (n=22) or a placebo (n=22) for eight weeks. Weight, height,
      body fat mass and systolic and diastolic blood pressure were measured at baseline
      and after intervention. The fasting blood glucose, insulin, HbA1c, total
      cholesterol, LDL C, HDL C, Apo lipoprotein A I and B were measured at baseline
      and endpoint. RESULTS: From 44 subjects participated in this study 37 completed
      the study. There were no significant differences in baseline characteristics,
      dietary intake and physical activity between groups. In the treatment group, the
      levels of fasting blood glucose, HbA1c, triglyceride, weight, BMI and body fat
      mass decreased significantly compared to baseline, but not in placebo group. No
      significant differences were observed in glycemic status indicators, lipid
      profile and anthropometric indicators between the groups at the end of
      intervention. CONCLUSION: These data suggest that cinnamon may have a moderate
      effect in improving glycemic status indicators.

PMID- 22973483
TI  - Seroprevalence and trend of dengue cases admitted to a government hospital, delhi
      - 5-year study (2006-2010): a look into the age shift.
AB  - BACKGROUND: Diagnosis of dengue infection is easily and best accomplished by
      demonstration of specific IgM antibodies in blood. We analyzed retrospectively
      the dengue IgM seropositivity available for samples obtained over a period of 5
      years (2006-2010) from patients with suspected dengue fever (DF)-like illness to
      investigate whether there was an overall increase in the dengue IgM prevalence
      over this period. METHODS: Blood samples were collected from patients with DF
      like febrile illnesses attending the Pediatric, Medicine, and Fever clinics of a
      Government hospital, Delhi. A total of 8138 individuals (suspected dengue cases)
      obtained over 5 years were tested for dengue specific IgM antibodies. Year wise,
      month wise, and age wise data on geographic distribution and clinical
      manifestations were analyzed. RESULTS: Of the 8138 samples, 1600 (19.66%) were
      positive for dengue specific IgM. The year 2006 had the highest number of
      reported cases, 761 (46.23%). In our study, the age group most commonly affected
      of all 5 years was 11-20 years. Out of the total 1600 cases admitted to the
      hospital between 2006 and 2010, 279 (58.9%) had DF, 178 (37.6%) had dengue
      hemorrhagic fever, and 16 (3.38%) had dengue shock syndrome. We found a high
      burden of dengue in young children and late adolescents in both rural and urban
      communities at a magnitude greater than previously described. INTERPRETATION AND
      CONCLUSION: We observed an increase in the dengue positive cases every alternate
      year, thereby indicating a possible role of herd immunity in northern India. We
      did not find a steady increase in the number of cases over 5 years. We found an
      increase in the number of positive cases in children and young adolescents.

PMID- 22973484
TI  - Caregiver Burden and its Determinants among the Family Members of Patients with
      Dementia in Iran.
AB  - BACKGROUND: "Caregiver Burden" is actually an expression addressing the adverse
      consequences of the care provided to the patients' with dementia. Review of the
      previous studies reveals a higher rate of depression and anxiety among the
      caregivers as compared to the general population. This study has been designed to
      evaluate the caregiver burden and then the factors influencing it among
      caregivers of patients with dementia in Iran. METHODS: In this cross-sectional
      study, 153 patients and their caregivers registered in the Memory Clinic in
      Roozbeh Hospital and Iranian Alzheimer Association (IAA) were included. Data
      collection scales were Iranian Version of Caregiver Burden, Global Deterioration
      scale and Barthel index. Multiple linear regression model was applied to
      determine the factors influencing the caregiver burden. RESULTS: Out of the 153
      patients, 90 were male. The mean age calculated for the patients and the
      caregivers was 77.1 and 53, respectively. The mean of caregiver burden was 55.2.
      Three variables, gender (P<0.01), education of the patient (P<0.005 for
      illiterate patients), and the patient's dependence on the caregiver for his/her
      daily tasks (P<0.000)) were correlated with a high level of burden on the
      caregiver. The recommended model explains 0.664% of the variance of the outcome
      variable. CONCLUSION: Presence of either moderate or higher levels of burden (58
      116) in more than 50% of the caregivers of these patients' highlights the need
      for more attention from health policy makers in Iran. Promoting the level of
      caregivers' quality of life along with enabling the patients in performing their
      daily tasks in order to reduce the imposed burden on caregivers' is recommended.

PMID- 22973485
TI  - National Cholesterol Education Program Adult Treatment Panel III Versus
      International Diabetic Federation Definition of Metabolic Syndrome, Which One is
      Associated with Diabetes Mellitus and Coronary Artery Disease?
AB  - BACKGROUND: A cluster of risk factors for cardiovascular diseases and type 2
      diabetes mellitus, which occur together more often than by chance alone, have
      been known as the metabolic syndrome. Various definitions have been proposed by
      different organizations over the past decade. This study was designed to evaluate
      a new definition of the metabolic syndrome for the prediction of diabetes
      mellitus among the Iranian population. METHODS: This study was carried out in an
      urban population, aged 20 to 74 years, from Yazd, a city in the center of Iran.
      The study is a part of the phase I of Yazd Healthy Heart Program, that is, a
      community-based intervention study for the prevention of cardiovascular disease.
      The significance level has been defined as P<0.05. RESULTS: Prevalence of the
      metabolic syndrome by the National Cholesterol Education Program Adult Treatment
      Panel III (NCEP ATP III) criteria was 21.3 +/- .017%, and by International
      Diabetes Federation (IDF) criteria it was 30.16 +/- .02%. The multivariate
      analysis showed that the most important relevant factors of diabetes mellitus
      were: Increased age and metabolic syndrome by both definitions of NCEP and IDF
      criteria, and also, the most important relevant factors of stable angina were:
      Increased age, male sex, and metabolic syndrome by only IDF definitions, but the
      NCEP definition of the metabolic syndrome cannot predict diabetes mellitus
      independent of age and sex. CONCLUSION: This study showed that increased age and
      metabolic syndrome are the most important relevant factors for diabetes mellitus,
      especially by using the IDF criteria for definition of the metabolic syndrome.

PMID- 22973486
TI  - Effects of Six Weeks of beta-alanine Administration on VO(2) max, Time to
      Exhaustion and Lactate Concentrations in Physical Education Students.
AB  - OBJECTIVES: Supplementation with beta-alanine has been proposed to improve
      performance in some exercises such as cycling and running. Also, it has been
      demonstrated that great deals of proton ions are produced in the skeletal muscles
      during exercise that result in acidosis, whereas beta-alanine may reduce this
      effect. Therefore, the aim of this study is to assess the effects of alanine
      supplementation on VO(2) max, time to exhaustion and lactate concentrations in
      physical education male students. METHODS: Thirty-nine male physical education
      students volunteered for this study. Participants were supplemented orally for 6
      week with either beta-alanine (5*400 mg/d) or placebo (5*400 mg dextrose/d),
      randomly. VO(2) max and time to exhaustion (TTE) with a continuous graded
      exercise test (GXT) on an electronically braked cycle ergometer; and serum
      lactate and glucose concentrations were measured before and after
      supplementation. RESULTS: Supplementation with beta-alanine showed a significant
      increase in VO(2) max (P<0.05) and a significant decrease in TTE and lactate
      concentrations (P<0.05). A significant elevation in lactate concentrations and a
      non significant increase in TTE were observed in placebo group. Plasma glucose
      concentrations did not change significantly in two groups after intervention.
      CONCLUSION: It can be concluded that beta-alanine supplementation can reduce
      lactate concentrations during exercise and thus can improve exercise performance
      in endurance athletes.

PMID- 22973487
TI  - Evaluation of Work-related Psychosocial and Ergonomics Factors in Relation to Low
      Back Discomfort in Emergency Unit Nurses.
AB  - BACKGROUND AND AIM: High prevalence of low back pain is one of the most common
      problems among nurses. The aim of this study was to evaluate the relation of the
      intensity of low back discomfort to two low back pain contributor factors
      (Ergonomics risk factors and psychosocial factors). METHODS: This cross-sectional
      survey was conducted on 120 emergency unit nurses in Esfahan. Job content,
      ergonomics hazards and nordic questionnaire were used in that order for daily
      assessment of Psychosocial and Ergonomics factors and the intensity of low back
      discomfort. Nurses were questioned during a 5-week period, at the end of each
      shift work. The final results were analyzed with SPSS software18/PASW by using
      Spearman, Mann-Whitney and Kolmogorov-Smirnove test. RESULTS: There was a
      significant relationship between work demand, job content, social support and
      intensity of low back discomfort (P value <0.05). But, there was not any link
      between intensity of low back discomfort and job control. Also, there was
      significant relationship between intensity of low back discomfort and ergonomics
      risk factors. CONCLUSION: This study showed an indirect relationship between the
      intensity of low back discomfort and social support. This study also confirmed a
      direct relationship between the intensity of low back discomfort and work demand,
      job content, ergonomics factors (Awkward Postures (rotating and bending), manual
      patient handling and repetitiveness, standing continuously more than 30 min). So,
      to decrease work related low back discomfort, psychosocial factors should be
      attended in addition to ergonomics factors.

PMID- 22973488
TI  - Pulmonary tuberculosis in mumbai, India: factors responsible for patient and
      treatment delays.
AB  - PURPOSE: To determine the factors responsible for patient delay and treatment
      delay in newly diagnosed sputum smear-positive pulmonary tuberculosis (TB)
      patients. METHODS: Study subjects (N = 150) were randomly selected from municipal
      health centers in Mumbai, India. Duration of symptoms, treatment, and reason for
      delay were assessed using interviews and medical records. We defined patient
      delay as presentation to a health care provider (HCP) >20 days of the onset of TB
      related symptoms and treatment delay as therapy initiated more than 14 days after
      the first consultation (for TB-related symptoms) with an HCP. RESULTS: Of the 150
      subjects, 29% had patient delays and 81% had treatment delays. In multivariable
      analysis, patient delay was significantly associated with the self-perception
      that initial symptoms were due to TB [odds ratio (OR) = 3.8, 95% confidence
      interval (CI) = 1.1-12.6] and perceived inability to pay for care (OR = 2.9, 95%
      CI = 1.2-7.1). Treatment delay was significantly associated with consulting a non
      allopathic provider (OR = 12.3, 95% CI = 1.4-105) and consulting >3 providers (OR
      = 5.0, 95% CI = 1.4-17.4). Patient interval was half the treatment interval
      (median days: 15 vs. 31). Women were slightly more likely to experience patient
      and treatment delays than men. For two-thirds of the patients, another TB patient
      was a source of TB-related knowledge, while health education material (16%) and
      television (10%) played a smaller role. CONCLUSION: Treatment delay, primarily
      due to diagnosis delay, was a greater problem than patient delay. Expanding
      public-public and public-private partnerships and regular training sessions for
      HCPs might decrease treatment delay. Media coverage and cured TB patients as peer
      advocates may help to reinforce TB-related health education messages.

PMID- 22973489
TI  - Intraosseous ganglion cyst of olecranon.
AB  - Intraosseous ganglia are benign cysts that usually can be seen in lower
      extremity; especially around ankle. These cysts have fewer incidences in upper
      extremity, mainly around the wrist. They are extremely rare in olecranon. These
      lesions are often asymptomatic. Patient was a 75-year-old man who had trauma many
      years ago. When he came to our clinic, he complained of severe pain around his
      elbow that he could not do ordinary activity. He had local tenderness in elbow
      and 30 degree limitation in extension. In radiography, lytic, multiloculated
      lesion existed in region of olecranon. After excisional biopsy was done, cavity
      was cleaned completely with curette and was filled with autogenous bone. At 10
      year follow-up, the patient was completely asymptomatic. Control radiograph
      showed cavity filled completely by bone; there was no evidence of relapse.

PMID- 22973490
TI  - The Effect of Education on Women's Practice Based on the Health Belief Model
      About Pap Smear Test.
AB  - INTRODUCTION: Cervical cancer is the most common gynecological cancer in Iran.
      The single most effective tool in reducing death due to cervical cancer is the
      use of pap smear as a screening tool. Therefore, the aim of this study was to
      determine the effectiveness of education based on Health Belief Model about
      giving pap smear in women. METHODS: This quasi-experimental study was performed
      on 70 women who referred to two health center in Kouhdasht (Lorestan- Iran). The
      samples were randomly divided in two groups (35 in intervention group and 35 in
      control group). The data were collected by a validated and reliable
      questionnaire. Interventions were run based on Health Belief Model during three
      sessions only for intervention group. Each educational session was for 45-60 min.
      The independent t-test and paired t-test were used to analyze data. A two-tailed
      P value lower than 0.05 was considered statistically significant. RESULT:
      According to results, the mean scores of knowledge were significantly different
      between two groups after intervention (P < 0.001). The mean scores of the model
      variables (perceived susceptibility and severity, perceived benefits, and
      barriers) had no significant difference in the two groups before intervention,
      but after intervention had significant difference between the two groups (P <
      0.001). CONCLUSION: Designing and executing health education programs based on
      health belief model can promote the practice of women regarding to pap smear
      tests.

PMID- 22973491
TI  - Leptospirosis as a still unknown and underappreciated disease.

PMID- 22973492
TI  - Social implications of malaria and their relationships with poverty.
AB  - In poor countries, tragically, people die unnecessarily. Having changed our
      understanding about issues related to poverty, even in the fight against malaria
      we must keep in mind a number of issues other than simple lack of economic
      resources. In this article we tried to discuss the various aspects that make
      malaria a disease closely related to poverty and the effects of malaria on the
      same poverty of patients who are affected. If you want the program to "Rool Back
      Malaria" to succeed, you must program interventions that improve the living
      conditions of populations in endemic area, individually and as communities. As
      has become clear that the discovery of an effective vaccine will not eradicate
      the disease, remains a fundamental understanding of mechanisms related to poverty
      that cause Malaria remains one of the major killers in the world, to help
      communities affected and individuals to prevent, cure properly and not being
      afraid of this ancient disease.

PMID- 22973493
TI  - Comparison of a DNA Based PCR Approach with Conventional Methods for the
      Detection of Mycobacterium tuberculosis in Morocco.
AB  - BACKGROUND: Worldwide, tuberculosis (TB) is a major public health problem and the
      rapid diagnosis and appropriate chemotherapy become the first priority and a
      serious challenge to improve TB treatment. In the objective of early TB diagnosis
      and rapid detection of Mycobacterium tuberculosis (MTB) in the clinical
      specimens, the utility of the Polymerase Chain Reaction (PCR) using the Insertion
      Sequence 6110 "IS6110" as target was compared to conventional methods. METHODS:
      Out of 305 patients with different clinical manifestations: suspected, new, drug
      relapse, drug failure and chronic cases were enrolled in this study and tested by
      mycobacteriological and PCR techniques for the investigation about the tubercle
      bacilli. RESULTS: The results of the in house "IS6110" PCR showed a good
      sensitivity (92.4%) and high specificity (98.0%), the positive and negative
      predictive values were 96.4 % and 95.3 % respectively. CONCLUSION: This study
      showed clearly that the PCR testing using the "IS6110" in the routine analysis is
      a potential tool for the rapid TB diagnosis, especially for critical cases and
      would be of great interest to help the clinician in the misdiagnosed critical
      cases by the traditional radiology.

PMID- 22973494
TI  - Rubella associated with hemophagocytic syndrome. First report in a male and
      review of the literature.
AB  - A 22-year-old man was admitted to our hospital because of fever, skin rash and
      epistaxis. Physical examination revealed fever (39.5 degrees C), generalized
      purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone
      marrow aspiration and biopsy showed hemophagocytosis with no evidence of
      malignant cells. Anti rubella IgM antibody were positive and the IgG titers
      increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have
      rubella-associated hemophagocytic syndrome. We report herein the first case in a
      man and the sixth case of rubella-associated hemophagocytic syndrome in the
      literature by search in Pub Med till March 2012.

PMID- 22973495
TI  - Iron and ferritin levels in saliva of patients with thalassemia and iron
      deficiency anemia.
AB  - Most of the techniques for measuring iron stores such as serum iron
      concentration, iron binding capacity, serum ferritin level, liver biopsy can be
      troublesome or invasive for patients with thalassemia. The salivary iron
      measurement could be of potential advantage being an easy and non invasive
      approach for diagnosis of iron deficiency and iron overload . The aim of this
      study was to compare the levels of iron and ferritin in saliva and serum of
      patients affected by thalassemia or iron deficiency anemia. For this purpose, 96
      patients with iron overload (71 with thalassemia major, 10 with thalassemia
      intermedia and 15 with thalassemia trait), 30 patients with iron deficiency
      anemia, and 35 healthy children as control group were involved in this study.
      Their saliva and serum iron and ferritin levels were measured. Iron and ferritin
      levels were higher in iron overload groups than in control group and lower in
      iron deficiency group (p<0.05). Furthermore serum and saliva iron and ferritin
      levels paralleled in all groups. In conclusion, iron and ferritin saliva can be
      routinely used for diagnosis of both iron overload and deficiency; furthermore
      this procedure may be an important advantage for blood donors being easily
      available and not invasive.

PMID- 22973496
TI  - Immunoglobulin gene repertoire in chronic lymphocytic leukemia: insight into
      antigen selection and microenvironmental interactions.
AB  - Immunogenetic analysis of the B cell receptors (BCRs) has been a richly rewarding
      field for unraveling the pathogenesis of human lymphomas, including CLL. A biased
      immunoglobulin gene repertoire is seen as evidence for selection of CLL
      progenitor cells by antigen. Additional corroborative evidence is provided by the
      differential prognosis of cases with distinct mutational status of the clonotypic
      BCRs. However, perhaps the strongest immunogenetic evidence for the importance of
      interactions with microenvironment in driving CLL development and evolution is
      the existence of subsets of patients with quasi-identical, stereotyped BCRs,
      collectively accounting for a remarkable one-third of the entire cohort. These
      observations have been instrumental in shaping the notion that CLL ontogeny is
      functionally driven and dynamic, rather than a simple stochastic process. From a
      clinical perspective, ample evidence indicates that immunogenetic information can
      be used for the biologically and clinically rational categorization of CLL, with
      important potential implications for basic, translational and clinical research.

PMID- 22973498
TI  - Penile ulcer atra related in patient with acute promyelocytic leukemia.

PMID- 22973497
TI  - Regulatory T-cells in chronic lymphocytic leukemia and autoimmune diseases.
AB  - Regulatory T-cells (Tregs) constitute a small subset of cells that are actively
      involved in maintaining self-tolerance, in immune homeostasis and in antitumor
      immunity. They are thought to play a significant role in the progression of
      cancer and are generally increased in patient with chronic lymphocytic leukemia
      (CLL). Their number correlates with more aggressive disease status and is
      predictive of the time to treatment, as well. Moreover, it is now clear that
      dysregulation in Tregs cell frequency and/or function may result in a plethora of
      autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus,
      myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative
      disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to
      develop approaches to deplete Tregs or inhibit their function in cancer and
      autoimmune disorders, as well.

PMID- 22973499
TI  - Toll-like Receptors in Chronic Lymphocytic Leukemia.
AB  - Toll-like receptors belong to the pattern recognition receptors family present on
      a variety of immune cells including normal and malignant B-cells. They act as
      immediate molecular sentinels of innate immunity but also act as a molecular
      bridge between the innate and the adaptive immune response; distinct Toll-like
      receptors are able to bind specific pattern molecules of bacteria, viruses and
      autoantigens. In this review we will briefly introduce the Toll-like receptor
      family and their expression pattern, signaling and function in the B cell
      context; following we will summarize the published data on TLR in chronic
      lymphocytic leukemia, and we will discuss their emerging role in the modulation
      of leukemia pathobiology.

PMID- 22973500
TI  - Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients
      with Idiopathic Thrombocytopenic Purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder
      characterized by auto antibody-mediated platelet destruction. Although the main
      cause of ITP remains unclear, but its relationship with some infection was
      demonstrated. In recent years, many studies have demonstrated improvement of
      platelet counts in ITP patients after treating Helicobacter pylori infection. The
      aim of this study was to investigate the effects of H. pylori eradication on
      platelet count response in Iranian ITP patients.A total of 26 patients diagnosed
      with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts
      were less than 100*10(3)/MUL. These patients were tested for H. pylori infection
      by Urea Breath Test and serum H. pylori antibody. All patients received triple
      therapy for 7 or 14 days to eradicate H. pylori infection. These patients
      followed for six months.Prevalence of H. pylori was 67.3%. H. pylori eradication
      achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete
      response (CR) and 11 (42.3%) were unresponsive. We did not find partial
      responders. There was a significant difference in the baseline platelet count of
      responders and non-responders patients (p<0.001). All responders had platelet
      count >=50*10(3)/MUL and all non-responders had platelet count
      <50*10(3)/MUL.Results of this study revealed that eradication therapy of H.
      pylori infection can improve platelet counts in ITP patients especially with mild
      thrombocytopenia and support routine detection and treatment of H. pylori
      infection in ITP patients in populations with a high prevalence of this
      infection.

PMID- 22973501
TI  - Nature of light correlations in ghost imaging.
AB  - We investigate the nature of correlations in Gaussian light sources used for
      ghost imaging. We adopt methods from quantum information theory to distinguish
      genuinely quantum from classical correlations. Combining a microscopic analysis
      of speckle-speckle correlations with an effective coarse-grained description of
      the beams, we show that quantum correlations exist even in 'classical'-like
      thermal light sources, and appear relevant for the implementation of ghost
      imaging in the regime of low illumination. We further demonstrate that the total
      correlations in the thermal source beams effectively determine the quality of the
      imaging, as quantified by the signal-to-noise ratio.

PMID- 22973502
TI  - Active plasmonics in WDM traffic switching applications.
AB  - With metal stripes being intrinsic components of plasmonic waveguides, plasmonics
      provides a "naturally" energy-efficient platform for merging broadband optical
      links with intelligent electronic processing, instigating a great promise for low
      power and small-footprint active functional circuitry. The first active
      Dielectric-Loaded Surface Plasmon Polariton (DLSPP) thermo-optic (TO) switches
      with successful performance in single-channel 10 Gb/s data traffic environments
      have led the inroad towards bringing low-power active plasmonics in practical
      traffic applications. In this article, we introduce active plasmonics into
      Wavelength Division Multiplexed (WDM) switching applications, using the smallest
      TO DLSPP-based Mach-Zehnder interferometric switch reported so far and showing
      its successful performance in 4*10 Gb/s low-power and fast switching operation.
      The demonstration of the WDM-enabling characteristics of active plasmonic
      circuits with an ultra-low power * response time product represents a crucial
      milestone in the development of active plasmonics towards real telecom and
      datacom applications, where low-energy and fast TO operation with small-size
      circuitry is targeted.

PMID- 22973503
TI  - Stroke and disorders of consciousness.
AB  - Objectives. To determine the severity of stroke and mortality in relation to the
      type of disturbance of consciousness and outcome of patients with disorders of
      consciousness. Patients and Methods. We retrospectively analyzed 201 patients.
      Assessment of disorders of consciousness is performed by Glasgow Coma Scale
      (Teasdale and Jennet, 1974) and the Diagnostic and Statistical Manual of Mental
      Disorders (Anonymous, 2000). The severity of stroke was determined by National
      Institutes of Health Stroke Scale (Lyden et al., 2011). Results. Fifty-four
      patients had disorders of consciousness (26.9%). Patients with disorders of
      consciousness on admission (P < 0.001) and discharge (P = 0.003) had a more
      severe stroke than patients without disturbances of consciousness. Mortality was
      significantly higher in patients with disorders of consciousness (P = 0.0001),
      and there was no difference in mortality in relation to the type of disturbance
      of consciousness. There is no statistically significant effect of specific
      predictors of survival in patients with disorders of consciousness. Conclusion.
      Patients with disorders of consciousness have a more severe stroke and higher
      mortality. There is no difference in mortality and severity of stroke between
      patients with quantitative and qualitative disorders of consciousness. There is
      no statistically significant effect of specific predictors of survival in
      patients with disorders of consciousness.

PMID- 22973504
TI  - Neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus (NLE) refers to a clinical spectrum of cutaneous,
      cardiac, and systemic abnormalities observed in newborn infants whose mothers
      have autoantibodies against Ro/SSA and La/SSB. The condition is rare and usually
      benign and self-limited but sometimes may be associated with serious sequelae. We
      review the pathophysiology, clinical features, and management of infants with
      this condition. Neonates with NLE should be managed at a tertiary care center.
      Multidisciplinary team involvement may also be indicated. In mothers with anti
      Ro/SSA and/or anti-La/SSB antibodies and infants with congenital heart block, the
      risk of recurrence in subsequent offspring is 17-25%. Therefore, careful
      monitoring of subsequent pregnancies with serial ultrasonography and
      echocardiography is essential.

PMID- 22973505
TI  - High Initial HIV/AIDS-Related Mortality and -Its Predictors among Patients on
      Antiretroviral Therapy in the Kagera Region of Tanzania: A Five-Year
      Retrospective Cohort Study.
AB  - We examined mortality rates and its predictors from a five years retrospective
      cohort data of HIV/AIDs patients attending care and treatment clinic in
      Biharamulo Tanzania. Cox regression analysis was used to identify predictors of
      mortality. Of the 546 patient records retrieved, the mean age was 37 years with
      median CD4 count of 156 cells. The mortality rate was 4.32/100 person years at
      risk with males having three times higher mortality compared to females. Starting
      Antiretroviral treatment with advanced disease state, body weight below 45 kegs,
      WHO stage 4 disease, and CD4 cells below 50 were main predictors of mortality.
      Promoting early voluntary counselling and testing should be given a priority to
      facilitate timely start of treatment.

PMID- 22973506
TI  - Association of interferon-alpha and ribavirin-induced thyroid dysfunction with
      severity of disease and response to treatment in pakistani asian patients of
      chronic hepatitis C.
AB  - Objective. To determine the association of thyroid dysfunction with the severity
      of the disease and response to treatment in patients of chronic hepatitis C.
      Design. Cohort study. Patients. One hundred and sixty seven noncirrhotic chronic
      hepatitis C patients were grouped into treatment group (n = 107) and control
      group (n = 60). Measurements. Baseline S. ALT and S. AST by IFCC and S. TSH, S.
      free T4, and S.T3 level were measured by chemiluminescence method. The severity
      of the disease was measured by Knodell histopathological index (HPI) on liver
      biopsy. Study group patients underwent 24-weeks IFN and ribavirin therapy and
      thyroid functions were determined at weeks 0, 12, and 24. Response to therapy was
      determined by PCR-HCV test. Results. 20 treated patients (18.69%) developed
      thyroid dysfunction with relative risk (RR) of 11.25 and attributable risk (AR)
      of 91%. Females were at higher risk. Hypothyroidism was common than
      hyperthyroidism. There was no significant association between thyroid dysfunction
      and severity of the disease (P = 0.81) and response to therapy (P = 0.79).
      Conclusion. Interferon-alpha and ribavirin therapy induces thyroid dysfunction in
      chronic hepatitis C patients. There is no association between severity of disease
      and response to therapy with interferon-induced thyroid dysfunction.

PMID- 22973507
TI  - Rethinking social support and conflict: lessons from a study of women who have
      separated from abusive partners.
AB  - Relationships have both positive and negative dimensions, yet most research in
      the area of intimate partner violence (IPV) has focused on social support, and
      not on social conflict. Based on the data from 309 English-speaking Canadian
      women who experienced IPV in the past 3 years and were no longer living with the
      abuser, we tested four hypotheses examining the relationships among severity of
      past IPV and women's social support, social conflict, and health. We found that
      the severity of past IPV exerted direct negative effects on women's health.
      Similarly, both social support and social conflict directly influenced women's
      health. Social conflict, but not social support, mediated the relationships
      between IPV severity and health. Finally, social conflict moderated the
      relationships between social support and women's health, such that the positive
      effects of social support were attenuated in the presence of high levels of
      social conflict. These findings highlight that routine assessments of social
      support and social conflict and the use of strategies to help women enhance
      support and reduce conflict in their relationships are essential aspects of
      nursing care.

PMID- 22973508
TI  - Assessment of Status of rpoB Gene in FNAC Samples of Tuberculous Lymphadenitis by
      Real-Time PCR.
AB  - Introduction. Multidrug resistance tuberculosis (MDR TB), the combined resistance
      of Mycobacterium tuberculosis to isoniazid (INH) and rifampin (RFM) is a major
      public health problem in India as it ranks second among the MDR-TB high burden
      countries worldwide. WHO recommends RFM resistance as a "surrogate marker" for
      detecting MDR. FNAC is the most widely used noninvasive investigative technique
      for TB lymphadenitis. Real-time polymerase chain reaction, an extremely versatile
      technique can be used for the timely detection and treatment of MDR TB by
      assessing RFM resistance status in the FNAC samples of TB lymphadenitis. Aim. To
      assess the status of rpoB gene by real-time PCR in FNAC samples of TB
      lymphadenitis. Materials and Methods. Thirty FNAC samples from patients with
      persistent LAP or appearance of new LAP after 5 months or more of Anti Tubercular
      Treatment were assessed for status of rpoB gene by Real-Time PCR using probe
      covering the "hot spot resistance" region of the rpoB gene. Result. By using
      probe covering codons 531 and 526 of rpoB gene, we could detect 17 of 30 (56.7%)
      rifampin resistant isolate. The PCR could detect Mtb DNA in 100% of cases.
      Conclusion. Use of molecular methods like Real-Time PCR for detection of MDR-TB
      in FNAC samples is time saving, logical and economical approach over the culture
      based method.

PMID- 22973509
TI  - Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients
      with Diabetic Peripheral Neuropathic Pain.
AB  - We summarize efficacy and safety findings from 4 double-blind, placebo
      controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance
      of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in
      patients with diabetic peripheral neuropathic pain (DPNP). In all placebo
      controlled studies, duloxetine showed significantly (P <= .01) greater reduction
      in pain severity (weekly mean of 24-hour average pain severity ratings, primary
      outcome measure) compared with placebo. In all placebo-controlled studies,
      duloxetine showed significantly (P <= .05) greater improvement on brief pain
      inventory-Interference ratings. Patient global impression of improvement ratings
      were superior to placebo (P <= .01) for duloxetine patients in all placebo
      controlled studies. Response rates (based on 30% pain reduction) ranged from 57%
      to 68% for duloxetine and from 35% to 47% for placebo and were statistically
      significantly different (P <= .01) between treatment groups in 3 out of 4
      studies. The open-label study showed maintenance of analgesic effect of
      duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients
      discontinued because of adverse events (placebo groups: 2.6% to 7.4%). Most
      commonly reported treatment-emergent adverse events were nausea, somnolence, and
      headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the
      management of DPNP.

PMID- 22973510
TI  - Pulmonary Hypertension Secondary to COPD.
AB  - The development of pulmonary hypertension in COPD adversely affects survival and
      exercise capacity and is associated with an increased risk of severe acute
      exacerbations. Unfortunately not all patients with COPD who meet criteria for
      long term oxygen therapy benefit from it. Even in those who benefit from long
      term oxygen therapy, such therapy may reverse the elevated pulmonary artery
      pressure but cannot normalize it. Moreover, the recent discovery of the key roles
      of endothelial dysfunction and inflammation in the pathogenesis of PH provides
      the rationale for considering specific pulmonary vasodilators that also possess
      antiproliferative properties and statins.

PMID- 22973512
TI  - Effect of sertraline on uremic pruritus improvement in ESRD patients.
AB  - Background. Although uremic pruritus is a common and upsetting problem of chronic
      kidney disease, there is no approved treatment for it. This study was undertaken
      to find the efficiency of sertraline as a possible treatment for uremic pruritus.
      Methods. 19 ESRD patients under hemodialysis with severe chronic pruritus were
      randomly selected to participate in this before-after clinical trial. Before and
      after starting treatment with sertraline, a detailed pruritus history was
      obtained and pruritus graded by the 30-item inventory of pruritus that patients
      based on priorities grade allocated to 3 classes. Subjects were treated with
      sertraline 50 mg oral daily for four months, with monthly assessments of pruritus
      symptoms. Results. Before treatment with sertraline, the grade of pruritus in 9
      (47.4%) patients was moderate and severe in 10 (52.6%) patients. After treatment,
      grade of pruritus in 11 (57.8%) patients was weak, 6 (31.5%) have moderate and
      only 2 (10.7%) patients have severe pruritus. Of 10 patients with severe
      pruritus, 5 (50%) patients experiencing weak pruritus, and 4 (40%) patients have
      moderate pruritus after treatment. Based on Wilcoxon signed-rank test, the
      difference between the grade of pruritus before and after treatment with
      sertraline was significant (P = 0.001). Conclusions. Although no definitive
      recommendation can be made regarding treatment of uremic pruritus, we found an
      increased antipruritic effect of sertraline in ESRD patients.

PMID- 22973511
TI  - Anti-inflammatory cytokines: important immunoregulatory factors contributing to
      chemotherapy-induced gastrointestinal mucositis.
AB  - "Mucositis" is the clinical term used to describe ulceration and damage of the
      mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic
      cancer chemotherapy and radiation therapy common symptoms include abdominal pain,
      bloating, diarrhoea, vomiting, and constipation resulting in both a significant
      clinical and financial burden. Chemotherapeutic drugs cause upregulation of
      stress response genes including NFkappaB, that in turn upregulate the production
      of proinflammatory cytokines such as interleukin-1beta (IL-1beta), Interleukin-6
      (IL-6), and tumour necrosis factor-alpha (TNF-alpha). These proinflammatory
      cytokines are responsible for initiating inflammation in response to tissue
      injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also
      released to limit the sustained or excessive inflammatory reactions. In the past
      decade, intensive research has determined the role of proinflammatory cytokines
      in development of mucositis. However, a large gap remains in the knowledge of the
      role of anti-inflammatory cytokines in the setting of chemotherapy-induced
      mucositis. This critical paper will highlight current literature available
      relating to what is known regarding the development of mucositis, including the
      molecular mechanisms involved in inducing inflammation particularly with respect
      to the role of proinflammatory cytokines, as well as provide a detailed
      discussion of why it is essential to consider extensive research in the role of
      anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective
      targeted treatment strategies can be developed.

PMID- 22973513
TI  - Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney
      Function Association.
AB  - Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease,
      but the association between HDLc and the estimated glomerular filtration rate
      (eGFR) in the general population is unclear. We investigated the HDLc-eGFR
      association in nondiabetic Han Chinese (HC, n = 1100), West Africans (WA, n =
      1497), and African Americans (AA, n = 1539). There were significant differences
      by ancestry: HDLc was positively associated with eGFR in HC (beta = 0.13, P <
      0.0001), but negatively associated among African ancestry populations (WA: -0.19,
      P < 0.0001; AA: -0.09, P = 0.02). These differences were also seen in nationally
      representative NHANES data (among European Americans: 0.09, P = 0.005; among
      African Americans -0.14, P = 0.03). To further explore the findings in African
      ancestry populations, we investigated the role of an African ancestry-specific
      nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1.
      Among AA, an inverse HDLc-eGFR association was observed only with the risk
      genotype (-0.38 versus 0.001; P = 0.03). This interaction was not seen in WA. In
      summary, counter to expectation, an inverse HDLc-eGFR association was observed
      among those of African ancestry. Given the APOL1 * HDLc interaction among AA,
      genetic factors may contribute to this paradoxical association. Notably, these
      findings suggest that the unexplained mechanism by which APOL1 affects kidney
      disease risk may involve HDLc.

PMID- 22973514
TI  - Elevated Serum Carboxymethyl-Lysine, an Advanced Glycation End Product, Predicts
      Severe Walking Disability in Older Women: The Women's Health and Aging Study I.
AB  - Advanced glycation end products (AGEs) have been implicated in the pathogenesis
      of sarcopenia. Our aim was to characterize the relationship between serum
      carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking
      disability (inability to walk or walking speed <0.4 m/sec) over 30 months of
      followup in 394 moderately to severely disabled women, >=65 years, living in the
      community in Baltimore, Maryland (the Women's Health and Aging Study I). During
      followup, 154 (26.4%) women developed severe walking disability, and 23 women
      died. Women in the highest quartile of serum CML had increased risk of developing
      of severe walking disability in a multivariate Cox proportional hazards model,
      adjusting for age and other potential confounders. Women with elevated serum CML
      are at an increased risk of developing severe walking disability. AGEs are a
      potentially modifiable risk factor. Further work is needed to establish a causal
      relationship between AGEs and walking disability.

PMID- 22973515
TI  - Do depressive traits and hostility predict age-related decline in general
      intelligence?
AB  - Certain personality traits are likely to be associated with stress and distress
      through the lifespan, and as a consequence these traits may influence the rate of
      age-related cognitive decline. The present study uses data from the Glostrup 1914
      cohort to analyze potential effects of personality on decline in general
      intelligence over a 30-year period. The Minnesota Multiphasic Personality
      Inventory was administered at a 50-year baseline exam, and from this inventory
      the Obvious Depression Scale and an abbreviated version of the Cook-Medley
      Hostility Scale were derived. At the 50-year baseline and at the 60-, 70-, and 80
      year followups the full version of Wechsler's Adult Intelligence Scale (WAIS) was
      administered to 673, 513, 136, and 184 participants. Mixed effects statistical
      models were used to evaluate both the effect of the personality scores on level
      of intelligence and the interaction between the personality scores and the time
      since followup. Analyses were adjusted for demographic background and a wide
      range of lifestyle factors. Both obvious depression and hostility were negatively
      associated with level of intelligence, but personality scores did not influence
      rate of decline in general intelligence.

PMID- 22973516
TI  - Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a
      Pure Amerindian Ethnic Group in Mexico.
AB  - Multiple Sclerosis (MS) is a highly polymorphic disease characterized by
      different neurologic signs and symptoms. In MS, racial and genetic factors may
      play an important role in the geographic distribution of this disease. Studies
      have reported the presence of several protective alleles against the development
      of autoimmune disorders. In the case of MS, however, they help define MS as a
      complex disease, and confirm the importance of environmental agents as an
      independent variable not associated with ethnicity. We carried out an on-site
      epidemiological study to confirm the absence of MS or NMO among Lacandonians, a
      pure Amerindian ethnic group in Mexico. We administered a structured interview to
      5,372 Lacandonians to assess by family background any clinical data consistent
      with the presence of a prior demyelinating event. Every participating subject
      underwent a comprehensive neurological examination by a group of three members of
      the research team with experience in the diagnosis and treatment of demyelinating
      disorders to detect clinical signs compatible with a demyelinating disease. We
      did not find any clinical signs compatible with multiple sclerosis among study
      participants.

PMID- 22973517
TI  - Obstacles to obtaining optimal physiotherapy services in a rural community in
      southeastern Nigeria.
AB  - Background. Many people continue to live with physical disabilities across the
      globe, especially in rural Africa despite expertise of Physiotherapists and
      available evidence of effectiveness of Physiotherapy. Objective. To determine the
      obstacles to obtaining Optimal Physiotherapy services in a rural community in
      Southeastern Nigeria. Methods. Population-based cross-sectional study of
      individuals and health facilities in a rural community in Southeastern Nigeria.
      Results. The obstacles to obtaining optimal physiotherapy services in this
      community were unavailability of physiotherapy services, poor knowledge of health
      workers and community dwellers of the roles and scope of physiotherapy, poor
      health care seeking behavior of community dwellers, patronage of traditional
      health workers, and poor referral practices by health workers. Conclusion. Rural
      health workers in Nkanu West Local Government and other rural communities in
      Nigeria and Africa should be educated on the roles and scope of physiotherapy.
      There is a need for raising awareness of the management options for
      movement/functional problems for rural indigenous communities in Nigeria in
      particular and Africa in general. Physiotherapists should be made aware of the
      growing need for physiotherapy in rural areas of Nigeria and Africa largely
      comprising of the elderly.

PMID- 22973519
TI  - Overview of hepatocellular adenoma in Japan.
AB  - Hepatocellular adenoma (HCA) is generally a benign hepatocellular tumor arising
      in a nonfibrotic/cirrhotic liver, and recently four major subgroups were
      identified based on genotype and phenotype classification from Europe. HCA is
      rare in Asian countries including Japan, and there have been few studies
      regarding the subgroups of HCA in Japan. We surveyed subgroups of HCA in 13
      patients (7 women) in Japan, based on the phenotypic classification. As results,
      we identified 2 hepatocyte nuclear factor (HNF) 1alpha-inactivated HCAs (15%),
      two beta-catenin-activated HCAs (15%), 5 inflammatory HCAs (39%), and 4
      unclassified HCAs (29%). The use of oral contraceptives was found only in 2
      unclassified HCAs (29%). Rather low percentage of female patients and use of oral
      contraceptives appear to be common clinicopathological features in Japan and also
      East Asian countries. Furthermore, a group of possible inflammatory HCAs
      characterized by strong immunoreactivity for serum amyloid A (SAA) was found in
      patients with alcoholic cirrhosis. The inflammatory HCA/SAA-positive
      hepatocellular neoplasm in alcoholic cirrhosis may be a new entity of HCA, which
      may have potential of malignant transformation. Further studies are needed to
      clarify genetic changes, monoclonality, and pathogenesis of this new type of
      hepatocellular neoplasm.

PMID- 22973520
TI  - A Complex Interplay between Wnt/beta-Catenin Signalling and the Cell Cycle in the
      Adult Liver.
AB  - Canonical Wnt signalling, governed by its effector beta-catenin, is known for a
      long time as playing an important role in development, tissue homeostasis, and
      cancer. In the liver, it was unravelled as both an oncogenic pathway involved in
      a subset of liver cancers and a physiological signalling identified as the
      "zonation-keeper" of the quiescent liver lobule. This duality has encouraged to
      explore the role of canonical Wnt in liver regeneration and liver-cell
      proliferation mainly using murine genetic models of beta-catenin overactivation
      or inactivation. These studies definitely integrate Wnt signalling within the
      hepatic network driving regeneration and proliferation. We will review here the
      current knowledge concerning the mitogenic effect of Wnt, to switch on its
      specific role in the liver, which is quiescent but with a great capacity to
      regenerate. The duality of beta-catenin signalling, associated both with liver
      quiescence and liver-cell proliferation, will be brought forward.

PMID- 22973522
TI  - Effect of residents' previous laparoscopic surgery experience on initial robotic
      suturing experience.
AB  - Objective. To assess the impact of gynecology residents' previous laparoscopic
      experience on the learning curve of robotic suturing techniques and the value of
      initial structured teaching in dry lab prior to surgery. Methods. Thirteen
      gynecology residents with no previous robotic surgery experience were divided
      into Group 1, consisting of residents with 2 or fewer laparoscopic experiences,
      and Group 2, consisting of residents with 3 or more laparoscopic experiences.
      Group 1 had a dry-laboratory training in suturing prior to their initial
      experience in the operating room. Results. For all residents, it took on average
      382 +/- 159 seconds for laparoscopic suturing and 326 +/- 196 seconds for robotic
      suturing (P = 0.12). Residents in Group 1 had a lower mean suture time than
      residents in Group 2 for laparoscopic suturing (P = 0.009). The residents in
      Group 2, however, had a lower mean suture time on the robot compared to Group 1
      (P = 0.5). Conclusion. Residents with previous laparoscopic suturing experience
      may gain more from a robotic surgery experience than those with limited
      laparoscopic surgery experience. In addition, dry lab training is more efficient
      than hands-on training in the initial phase of teaching for both laparoscopic and
      robotic suturing skills.

PMID- 22973518
TI  - Cell signals influencing hepatic fibrosis.
AB  - Liver fibrosis is the result of the entire organism responding to a chronic
      injury. Every cell type in the liver contributes to the fibrosis. This paper
      first discusses key intracellular signaling pathways that are induced during
      liver fibrosis. The paper then examines the effects of these signaling pathways
      on the major cell types in the liver. This will provide insights into the
      molecular pathophysiology of liver fibrosis and should identify therapeutic
      targets.

PMID- 22973521
TI  - Watch the GAP: Emerging Roles for IQ Motif-Containing GTPase-Activating Proteins
      IQGAPs in Hepatocellular Carcinoma.
AB  - IQ motif-containing GTPase-activating proteins IQGAP1 and IQGAP2 are highly
      homologous multidomain scaffolding proteins. Their major function consists of
      integration of Rho GTPase and Ca(2+)/calmodulin signals with cell adhesive and
      cytoskeletal reorganizational events. Recent studies showed that they play an
      important role in carcinogenesis. There is growing evidence that IQGAP2 is a
      novel tumor suppressor counteracting the effects of IQGAP1, an oncogene, in
      several cancers, especially in hepatocellular carcinoma (HCC). While HCC is
      highly prevalent and one of the deadliest cancers worldwide, the signaling
      pathways involved are not fully understood and treatment of advanced disease
      still represents an area of high unmet medical need. This paper compiles various
      findings from studies in mouse models, cell lines, and patient samples that
      support future development of IQGAPs into new therapeutic targets. It also
      discusses distinct features of IQGAP2 in an attempt to provide insight into the
      mechanism of the seemingly paradoxical opposing roles of the two very similar
      IQGAP proteins in carcinogenesis.

PMID- 22973523
TI  - Assessment of exercise testing after repair of tetralogy of fallot.
AB  - Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart
      disease. The aim of this study was to examine the exercise performance of young
      patients following the repair of TOF and to assess the influence of different
      variables related to the surgical repair on exercise testing. This study was
      conducted on 21 patients (16 males and 5 females) operated on for TOF compared to
      15 healthy age- and sex-matched control children. The patients' median age at
      time of the study was 8 years (range 5-13 years) while age at surgical repair was
      5 +/- 2.1 years (range 2-10 years). Patients were subjected to 2D and color
      Doppler echocardiographic examination. Treadmill exercise stress testing was
      performed for all subjects according to modified Bruce protocol. The resting ECGs
      of all patients revealed normal sinus rhythm and RBBB. Cases had lower exercise
      capacity when compared to control subjects and those with aortopulmonary shunt
      showed significantly lower exercise performance when compared to those without
      aortopulmonary shunt. In conclusions, exercise tolerance after total correction
      of TOF is slightly impaired on short-term followup with more affection among
      patients with previous aortopulmonary shunts. The present study did not reveal
      any serious ventricular arrhythmia.

PMID- 22973524
TI  - Use of the Bonfils Intubation Fiberscope in patients with limited mouth opening.
AB  - Airway management of patients with very limited mouth opening remains a challenge
      for the anaesthetist. We describe the use of the Bonfils Intubation Fiberscope
      for awake intubation in two patients with a very limited mouth opening. In the
      first case, a 60-year-old 80 kg female, scheduled for a right modified radical
      mastectomy for infiltrating ductal carcinoma (15 mm mouth opening, a short thick
      neck, limited neck extension, and a Mallampati class 4 airway), the Bonfils was
      advanced via the retromolar technique. In the second patient, a 34-year-old male,
      scheduled for a surgical tracheotomy for right tonsillar cancer, due to a
      neoplastic infiltration of the right temporomandibular joint (7 mm mouth opening
      and limited neck movement), the Bonfils was advanced using the midline approach.
      The Bonfils is a reusable, rigid, straight fiberoptic device with a curved tip,
      is 5 mm in diameter, and has several advantages: it is quick and easy to use,
      more cost effective than a flexible fiberscope, and is safe in expert hands,
      thanks to its smaller diameter. Our conclusion is that awake BIF intubation is a
      reliable, atraumatic, and well-tolerated procedure to secure a safe airway in
      patients with a limited mouth opening.

PMID- 22973525
TI  - In vitro contracture test results and anaesthetic management of a patient with
      emery-dreifuss muscular dystrophy for cardiac transplantation.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is a hereditary neuromuscular disorder
      characterized by slowly progressive muscle weakness, early contractures, and
      dilated cardiomyopathy. We reported an uneventful general anaesthesia using total
      intravenous anaesthesia (TIVA) for cardiac transplantation in a 19-year-old woman
      suffering from EDMD. In vitro contracture test results of two pectoralis major
      muscle bundles of the patient suggest that exposition to triggering agents does
      not induce a pathological sarcoplasmic calcium release in the lamin A/C
      phenotype. However, due to the lack of evidence in the literature, we would
      recommend TIVA for patients with EDMD if general anaesthesia is required.

PMID- 22973526
TI  - Ruptured granulosa cell tumor of the ovary as a cause of acute abdomen in
      postmenopausal woman.
AB  - Acute abdomen with hemoperitoneum is a very rare entity in postmenopausal women
      due to gynecologic conditions. A 54-year-old, postmenopausal woman was brought to
      emergency department with severe abdominal pain. Physical examination revealed
      acute abdomen findings with 15 cm pelvic mass on the right adnexal region.
      Immediate exploratory laparotomy was performed. During laparotomy 1000 cc of
      bloodstained fluid, ruptured and actively bleeding large mass arising from right
      ovary was observed. Right salpingo-oopherectomy was performed in emergency
      conditions, and pathology report revealed an adult type of granulosa cell tumor.
      After this result, staging surgery was performed and patient was diagnosed as
      granulosa cell tumor stage 1 c. Cisplatin, etoposide, and bleomycin chemotherapy
      was given. Clinicians should be aware of granulosa cell tumors which may occur at
      any age and prone to rupture. Frozen section will be helpful in order to avoid
      incomplete surgeries especially in postmenopausal women presented with intra
      abdominal bleeding.

PMID- 22973527
TI  - Complete corpus callosum agenesis: can it be mild?
AB  - Corpus callosum agenesis is a relatively common brain malformation. It can be
      isolated or included in a complex alteration of brain (or sometimes even whole
      body) morphology. Etiology and pathogenetic mechanisms have been better
      understood in recent years due to the availability of more adequate animal models
      and the relevant progresses in developmental neurosciences. We present the case
      of a girl with a complete agenesis of the corpus callosum discovered at birth.
      She had mild learning difficulties, but reached satisfactory levels of autonomy
      after an individually tailored rehabilitative treatment. Her story is discussed
      in light of recent findings, which emphasize the possibility to exploit brain
      plasticity and the utility of an individually tailored approach, defined on the
      basis of a dialogue with the family and the patient.

PMID- 22973528
TI  - Haemothorax and thoracic spine fractures in the elderly.
AB  - Both osteoporotic fractures and pleural effusions are frequently observed in
      medicine. However, rarely does one associate a hemorrhagic pleural effusion with
      a thoracic spinal fracture when the patient has not sustained massive trauma. In
      this paper, we discuss two cases where seemingly insignificant low-energy trauma
      precipitated massive haemothoraces in elderly patients with underlying
      osteoporosis, ultimately resulting in their immediate causes of death. This paper
      serves to remind health care professionals of the importance of using caution
      when moving elderly patients as well as to consider thoracic spinal fracture as a
      potential explanation for a hemorrhagic pleural effusion of undetermined
      etiology.

PMID- 22973529
TI  - Efficacy of Corticosteroids Alone in the Eradication of Factor VIII Inhibitor in
      an Old Female with Idiopathic Acquired Haemophilia A: Description of a Case.
AB  - Acquired haemophilia A (AHA) is a rare and serious disorder mainly affecting
      elderly patients. It is caused by the production of autoantibodies directed
      against coagulation factors; patients present with spontaneous bleeding,
      potentially fatal, in the absence of familial or personal history. Autoimmune
      disorders, infections, solid and hematologic tumors, and drugs are predisposing
      factors, but up to 50 percent of cases remain unexplained. The diagnosis of AHA
      is confirmed by specific laboratory tests; and the therapy is a clinical
      challenge, due to the fact that older patients are often affected by
      comorbidities. By passing agents may be used when persistent bleeding or
      haemodynamic instability is observed; corticosteroids, alone or with
      immunosuppressive therapy, are necessary to inhibit the production of the
      autoantibodies. We describe a case in which steroids in monotherapy successfully,
      safely, and persistently inhibited the production of anti-Factor VIII antibodies,
      in an old patient admitted after rheumatologic consult.

PMID- 22973530
TI  - Pulmonary Arterial Hypertension in Adult-Onset Still's Disease: Rapid Response to
      Anakinra.
AB  - Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized
      by spiking quotidian fever, rash, chronic arthralgia, leukocytosis, and
      occasional pulmonary involvement such as pleural effusion and transient pulmonary
      infiltrates. Pulmonary arterial hypertension (PAH) is a rare pulmonary
      complication of AOSD, and we are aware of only 5 cases reported in the
      literature. We report the case of a 27-year-old woman of Middle Eastern descent,
      with a 7-year history of AOSD, who developed severe pulmonary arterial
      hypertension (PAH). After unsuccessful exposure to various immunosuppressive
      regimens, shortly following the initiation of anakinra, an interleukin-1 (IL-1)
      receptor antagonist, her disease became quiescent and the PAH resolved. With this
      case report, we hope to show that anakinra, either by virtue of controlling the
      overall inflammation in AOSD, or by direct effect on the pulmonary
      microangiopathy, can improve severe PAH.

PMID- 22973531
TI  - Laproscopic management of wandering biliary ascariasis.
AB  - Ascariasis is one of the most common helminthic diseases in humans, occurring
      mostly in countries with low standards of public health and hygiene, thereby
      making ascariasis highly endemic in developing countries. In endemic areas, 30%
      of adults and 60-70% of children harbour the adult worm. Biliary ascariasis is a
      rare cause of obstructive jaundice. Conventional management involves endoscopic
      extraction of worm. We are reporting a rare case of ascaris which induced
      extrahepatic biliary obstruction in a young male who presented with acute
      cholangitis. The ascaris was removed by laparoscopic exploration of the common
      bile duct. Postoperative period was uneventful.

PMID- 22973532
TI  - Persistence of the sciatic artery: a case report of a combined (complete and
      incomplete) type causing leg ischemia.
AB  - Persistent sciatic artery is a very uncommon embryologic vascular variant, with a
      prevalence of 0.05% based on angiographic studies. Two different types of this
      anomaly can occur, complete or incomplete, on the basis of the relationship
      between sciatic artery and femoral artery. Although many of these patients are
      asymptomatic, it may represent a threat to the viability of the lower extremity
      because of atherosclerotic degeneration resulting in aneurysmal dilatation,
      occlusive thrombosis, or embolic phenomena with distal complication. We present a
      case of a 64-year-old man with combined, complete and incomplete, type of
      persistent sciatic artery causing ischemic ulcer of the first toe.

PMID- 22973533
TI  - Mitochondria and Parkinson's disease.

PMID- 22973534
TI  - Cadherin cell adhesion system in canine mammary cancer: a review.
AB  - Cadherin-catenin adhesion complexes play important roles by providing cell-cell
      adhesion and communication in different organ systems. Abnormal expression of
      cadherin adhesion molecules constitutes a common phenomenon in canine mammary
      cancer and has been frequently implicated in tumour progression. This paper
      summarizes the current knowledge on cadherin/catenin adhesion molecules (E
      cadherin, beta-catenin, and P-cadherin) in canine mammary cancer, focusing on the
      putative biological functions and clinical significance of these molecules in
      this disease. This paper highlights the need for further research studies in this
      setting in order to elucidate the role of these adhesion molecules during tumour
      progression and metastasis.

PMID- 22973535
TI  - Evolutionary history and genome organization of DUF1220 protein domains.
AB  - DUF1220 protein domains exhibit the most extreme human lineage-specific (HLS)
      copy number increase of any protein coding region in the human genome and have
      recently been linked to evolutionary and pathological changes in brain size
      (e.g., 1q21-associated microcephaly). These findings lend support to the view
      that DUF1220 domain dosage is a key factor in the determination of primate (and
      human) brain size. Here we analyze 41 animal genomes and present the most
      complete account to date of the evolutionary history and genome organization of
      DUF1220 domains and the gene family that encodes them (NBPF). Included among the
      novel features identified by this analysis is a DUF1220 domain precursor in
      nonmammalian vertebrates, a unique predicted promoter common to all mammalian
      NBPF genes, six distinct clades into which DUF1220 sequences can be subdivided,
      and a previously unknown member of the NBPF gene family (NBPF25). Most
      importantly, we show that the exceptional HLS increase in DUF1220 copy number
      (from 102 in our last common ancestor with chimp to 272 in human; an average HLS
      increase of ~28 copies every million years since the Homo/Pan split) was driven
      by intragenic domain hyperamplification. This increase primarily involved a 4.7
      kb, tandemly repeated three DUF1220 domain unit we have named the HLS DUF1220
      triplet, a motif that is a likely candidate to underlie key properties unique to
      the Homo sapiens brain. Interestingly, all copies of the HLS DUF1220 triplet lie
      within a human-specific pericentric inversion that also includes the 1q12 C-band,
      a polymorphic heterochromatin expansion that is unique to the human genome. Both
      cytogenetic features likely played key roles in the rapid HLS DUF1220 triplet
      hyperamplification, which is among the most striking genomic changes specific to
      the human lineage.

PMID- 22973536
TI  - oPOSSUM-3: advanced analysis of regulatory motif over-representation across genes
      or ChIP-Seq datasets.
AB  - oPOSSUM-3 is a web-accessible software system for identification of over
      represented transcription factor binding sites (TFBS) and TFBS families in either
      DNA sequences of co-expressed genes or sequences generated from high-throughput
      methods, such as ChIP-Seq. Validation of the system with known sets of co
      regulated genes and published ChIP-Seq data demonstrates the capacity for oPOSSUM
      3 to identify mediating transcription factors (TF) for co-regulated genes or co
      recovered sequences. oPOSSUM-3 is available at http://opossum.cisreg.ca.

PMID- 22973537
TI  - Glucose, nitrogen, and phosphate repletion in Saccharomyces cerevisiae: common
      transcriptional responses to different nutrient signals.
AB  - Saccharomyces cerevisiae are able to control growth in response to changes in
      nutrient availability. The limitation for single macronutrients, including
      nitrogen (N) and phosphate (P), produces stable arrest in G1/G0. Restoration of
      the limiting nutrient quickly restores growth. It has been shown that glucose (G)
      depletion/repletion very rapidly alters the levels of more than 2000 transcripts
      by at least 2-fold, a large portion of which are involved with either protein
      production in growth or stress responses in starvation. Although the signals
      generated by G, N, and P are thought to be quite distinct, we tested the
      hypothesis that depletion and repletion of any of these three nutrients would
      affect a common core set of genes as part of a generalized response to conditions
      that promote growth and quiescence. We found that the response to depletion of G,
      N, or P produced similar quiescent states with largely similar transcriptomes. As
      we predicted, repletion of each of the nutrients G, N, or P induced a large (501)
      common core set of genes and repressed a large (616) common gene set. Each
      nutrient also produced nutrient-specific transcript changes. The transcriptional
      responses to each of the three nutrients depended on cAMP and, to a lesser
      extent, the TOR pathway. All three nutrients stimulated cAMP production within
      minutes of repletion, and artificially increasing cAMP levels was sufficient to
      replicate much of the core transcriptional response. The recently identified
      transceptors Gap1, Mep1, Mep2, and Mep3, as well as Pho84, all played some role
      in the core transcriptional responses to N or P. As expected, we found some
      evidence of cross talk between nutrient signals, yet each nutrient sends distinct
      signals.

PMID- 22973538
TI  - Quantitative trait loci affecting liver fat content in mice.
AB  - Nonalcoholic fatty liver disease, a condition in which excess fat accumulates in
      the liver, is strongly associated with the metabolic syndrome, including obesity
      and other related conditions. This disease has the potential to progress from
      steatosis to steatohepatitis, fibrosis, and cirrhosis. The recent increase in the
      prevalence of the metabolic syndrome is largely driven by changes in diet and
      activity levels. Individual variation in the response to this obesogenic
      environment, however, is attributable in part to genetic variation between
      individuals, but very few mammalian genetic loci have been identified with
      effects on fat accumulation in the liver. To study the genetic basis for
      variation in liver fat content in response to dietary fat, liver fat proportion
      was determined using quantitative magnetic resonance imaging in 478 mice from 16
      LG/J X SM/J recombinant inbred strains fed either a high-fat (42% kcal from fat)
      or low-fat (15% kcal from fat) diet. An analysis of variance confirmed that there
      is a genetic basis for variation in liver fat content within the population with
      significant effects of sex and diet. Three quantitative trail loci that
      contribute to liver fat content also were mapped.

PMID- 22973539
TI  - Tandem-repeat patterns and mutation rates in microsatellites of the nematode
      model organism Pristionchus pacificus.
AB  - Modern evolutionary biology requires integrative approaches that combine life
      history, population structure, ecology, and development. The nematode
      Pristionchus pacificus has been established as a model system in which these
      aspects can be studied in one organism. P. pacificus has well-developed genetic,
      genomic, and transgenic tools and its ecologic association with scarab beetles is
      well described. A recent study provided first mutation rate estimates based on
      mitochondrial genome sequencing and mutation accumulation line experiments that
      help resolve rather ancient evolutionary branches. Here, we analyzed the tandem
      repeat pattern and studied spontaneous mutation rates for microsatellite markers
      by using the previously generated mutation accumulation lines. We found that
      0.59%-3.83% of the genome is composed of short tandem repeats. We developed 41
      microsatellite markers, randomly chosen throughout the genome and analyzed them
      in 82 mutation accumulation lines after 142 generations. A total of 31 mutations
      were identified in these lines. There was a strong correlation between allele
      size and mutation rate in P. pacificus, similar to Caenorhabditis elegans. In
      contrast to C. elegans, however, there is no evidence for a bias toward multistep
      mutations. The mutation spectrum of microsatellite loci in P. pacificus shows
      more insertions than deletions, indicating a tendency toward lengthening, a
      process that might have contributed to the increase in genome size. The mutation
      rates obtained for individual microsatellite markers provide guidelines for
      divergence time estimates that can be applied in P. pacificus next-generation
      sequencing approaches of wild isolates.

PMID- 22973540
TI  - Location-dependent empirical thresholds for quantitative trait mapping.
AB  - The Churchill-Doerge approach toward constructing empirical thresholds has
      received widespread use in the genetic mapping literature through the past 16
      years. The method is valued for both its simplicity and its ability to preserve
      the genome-wide error rate at a prespecified level. However, the Churchill-Doerge
      method is not designed to maintain the local (comparison-wise) error rate at a
      constant level except in situations that are unlikely to occur in practice. In
      this article, we introduce the objective of preserving the local error rate at a
      constant level in the context of mapping quantitative trait loci in linkage
      populations. We derive a method that preserves the local error rate at a constant
      level, provide an application via simulation on a Hordeum vulgare population, and
      demonstrate evidence of the relationship between recombination and location bias.
      Furthermore, we indicate that this method is equivalent to the Churchill-Doerge
      method when several assumptions are satisfied.

PMID- 22973541
TI  - The Lsktm1 locus modulates lung and skin tumorigenesis in the mouse.
AB  - Alleles derived from skin tumor-resistant Car-R mice provide resistance to both
      skin and lung tumorigenesis over the susceptibility of the SWR/J strain. In an
      effort to map tumor modifier loci affecting both tumor types, we carried out a
      genetic linkage analysis in backcross SWR/J x (SWR/J x Car-R) mice and identified
      a locus (Lsktm1) on chromosome 1 linked to both skin (LOD score = 3.93) and lung
      (LOD score = 8.74) tumorigenesis. Two genes, Igfbp5 and Igfbp2, residing in this
      locus and belonging to the insulin-like growth factor binding protein family were
      expressed at significantly greater levels in normal lung tissue from cancer
      resistant Car-R mice than in cancer-susceptible SWR/J mice. Overexpression of the
      recombinant Igfbp5 and Igfbp2 genes in two lung cancer cell lines significantly
      inhibited clonogenicity (P < 0.0001). Collectively, we have identified a single
      polymorphic locus that affects skin and lung tumorigenesis and identify Igfbp5
      and Igfbp2 as candidate modifier genes of lung tumorigenesis.

PMID- 22973542
TI  - Genetic architecture of variation in the lateral line sensory system of
      threespine sticklebacks.
AB  - Vertebrate sensory systems have evolved remarkable diversity, but little is known
      about the underlying genetic mechanisms. The lateral line sensory system of
      aquatic vertebrates is a promising model for genetic investigations of sensory
      evolution because there is extensive variation within and between species, and
      this variation is easily quantified. In the present study, we compare the lateral
      line sensory system of threespine sticklebacks (Gasterosteus aculeatus) from an
      ancestral marine and a derived benthic lake population. We show that lab-raised
      individuals from these populations display differences in sensory neuromast
      number, neuromast patterning, and groove morphology. Using genetic linkage
      mapping, we identify regions of the genome that influence different aspects of
      lateral line morphology. Distinct loci independently affect neuromast number on
      different body regions, suggesting that a modular genetic structure underlies the
      evolution of peripheral receptor number in this sensory system. Pleiotropy and/or
      tight linkage are also important, as we identify a region on linkage group 21
      that affects multiple aspects of lateral line morphology. Finally, we detect
      epistasis between a locus on linkage group 4 and a locus on linkage group 21;
      interactions between these loci contribute to variation in neuromast pattern. Our
      results reveal a complex genetic architecture underlying the evolution of the
      stickleback lateral line sensory system. This study further uncovers a genetic
      relationship between sensory morphology and non-neural traits (bony lateral
      plates), creating an opportunity to investigate morphological constraints on
      sensory evolution in a vertebrate model system.

PMID- 22973543
TI  - Using near-infrared spectroscopy to resolve the species, gender, age, and the
      presence of Wolbachia infection in laboratory-reared Drosophila.
AB  - The aim of the study was to determine the accuracy of near-infrared spectroscopy
      (NIRS) in determining species, gender, age, and the presence of the common
      endosymbiont Wolbachia in laboratory-reared Drosophila. NIRS measures the
      absorption of light by organic molecules. Initially, a calibration model was
      developed for each study. An independent set with flies not involved in initial
      cross-validation was then used to validate the accuracy of each calibration
      model. Flies from the independent sets were correctly classified into Drosophila
      melanogaster and Drosophila simulans with 94% and 82% accuracy, respectively,
      whereas flies were successfully classified by gender with accuracy greater than
      90%. In the age grading test, correlation plots of the actual and predicted age
      for males and females of D. melanogaster and D. simulans were shown to be
      overlapping between the adjacent age groups. It is, however, possible to predict
      the age of flies as less than 9 days of age with 62-88% accuracy and flies that
      are equal to or older than 9 days of age with 91-98% accuracy. Finally, we used
      NIRS to detect the presence of Wolbachia in flies. Flies from the independent
      sets were successfully identified as infected or not infected with Wolbachia with
      approximately 90% accuracy. These results suggest that NIRS has the potential to
      quantify the species, gender, and presence of Wolbachia in fly populations.
      However, additional optimization of the protocol may be necessary before the
      technique can reliably estimate fly age.

PMID- 22973544
TI  - Uncovering networks from genome-wide association studies via circular genomic
      permutation.
AB  - Genome-wide association studies (GWAS) aim to detect single nucleotide
      polymorphisms (SNP) associated with trait variation. However, due to the large
      number of tests, standard analysis techniques impose highly stringent
      significance thresholds, leaving potentially associated SNPs undetected, and much
      of the trait genetic variation unexplained. Pathway- and network-based
      methodologies applied to GWAS aim to detect associations missed by standard
      single-marker approaches. The complex and non-random architecture of the genome
      makes it a challenge to derive an appropriate testing framework for such
      methodologies. We developed a rapid and simple permutation approach that uses
      GWAS SNP association results to establish the significance of pathway
      associations while accounting for the linkage disequilibrium structure of SNPs
      and the clustering of functionally related elements in the genome. All SNPs used
      in the GWAS are placed in a "circular genome" according to their location. Then
      the complete set of SNP association P values are permuted by rotation with
      respect to the genomic locations of the SNPs. Once these "simulated" P values are
      assigned, the joint gene P values are calculated using Fisher's combination test,
      and the association of pathways is tested using the hypergeometric test. The
      circular genomic permutation approach was applied to a human genome-wide
      association dataset. The data consists of 719 individuals from the ORCADES study
      genotyped for ~300,000 SNPs and measured for 51 traits ranging from physical to
      biochemical measurements. KEGG pathways (n = 225) were used as the sets of
      pathways to be tested. Our results demonstrate that the circular genomic
      permutations provide robust association P values. The non-permuted hypergeometric
      analysis generates ~1400 pathway-trait combination results with an association P
      value more significant than P <= 0.05, whereas applying circular genomic
      permutation reduces the number of significant results to a more credible 40% of
      that value. The circular permutation software ("genomicper") is available as an R
      package at http://cran.r-project.org/.

PMID- 22973545
TI  - Variant in the 5' untranslated region of insulin-like growth factor 1 receptor is
      associated with susceptibility to mastitis in cattle.
AB  - Mastitis is a common infectious disease of the mammary gland and generates large
      losses in the dairy industry. By means of positional cloning and functional
      analysis techniques, we here show that insulin-like growth factor 1 receptor
      (IGF1R) can possibly mediate susceptibility to mastitis through autophagy.
      Scanning the whole genome of cows (Bos taurus) that were susceptible or resistant
      to mastitis in the half-sib families revealed that susceptible cows had a
      relatively long stretch of cytosine residues (C stretch) in the 5' untranslated
      region of IGF1R. The forebrain embryonic zinc finger-like (FEZL) transcription
      factor, which was previously identified as a factor controlling mastitis
      resistance in the same half-sib families, bound the C stretch of IGF1R. The
      susceptible type of FEZL with a glycine stretch containing 13 glycines (13G) and
      the longer C stretch of IGF1R together enhanced expression of IGF1R. Enhancing
      IGF1R inhibited autophagy in response to Streptococcus agalactiae invasion of
      mammary epithelial cells, whereas treatment with rapamycin, a known inducer of
      autophagy, rescued it. Cows carrying the variant combination of 13GFEZL might be
      more susceptible to mastitis as the result of impaired autophagy. Our results
      suggest that IGF1R could control innate immunity in mammals and serve as a
      potential tool for preventing mastitis.

PMID- 22973546
TI  - Predicting adaptive phenotypes from multilocus genotypes in Sitka spruce (Picea
      sitchensis) using random forest.
AB  - Climate is the primary driver of the distribution of tree species worldwide, and
      the potential for adaptive evolution will be an important factor determining the
      response of forests to anthropogenic climate change. Although association mapping
      has the potential to improve our understanding of the genomic underpinnings of
      climatically relevant traits, the utility of adaptive polymorphisms uncovered by
      such studies would be greatly enhanced by the development of integrated models
      that account for the phenotypic effects of multiple single-nucleotide
      polymorphisms (SNPs) and their interactions simultaneously. We previously
      reported the results of association mapping in the widespread conifer Sitka
      spruce (Picea sitchensis). In the current study we used the recursive
      partitioning algorithm 'Random Forest' to identify optimized combinations of SNPs
      to predict adaptive phenotypes. After adjusting for population structure, we were
      able to explain 37% and 30% of the phenotypic variation, respectively, in two
      locally adaptive traits--autumn budset timing and cold hardiness. For each trait,
      the leading five SNPs captured much of the phenotypic variation. To determine the
      role of epistasis in shaping these phenotypes, we also used a novel approach to
      quantify the strength and direction of pairwise interactions between SNPs and
      found such interactions to be common. Our results demonstrate the power of Random
      Forest to identify subsets of markers that are most important to climatic
      adaptation, and suggest that interactions among these loci may be widespread.

PMID- 22973547
TI  - An assay to detect in vivo Y chromosome loss in Drosophila wing disc cells.
AB  - Loss of the Y chromosome in Drosophila has no impact on cell viability and
      therefore allows us to assay the impact of environmental agents and genetic
      alterations on chromosomal loss. To detect in vivo chromosome loss in cells of
      the developing Drosophila wing primordia, we first engineered a Y chromosome with
      an attP docking site. By making use of the PhiC31 integrase system, we site
      specifically integrated a genomic transgene encompassing the multiple wing hair
      (mwh) locus into this attP site, leading to a mwh(+)Y chromosome. This chromosome
      fully rescues the mwh mutant phenotype, an excellent recessive wing cell marker
      mutation. Loss of this mwh(+)Y chromosome in wing primordial cells then leads to
      manifestation of the mwh mutant phenotype in mwh-homozygous cells. The forming
      mwh clones permit us to quantify the effect of agents and genetic alterations by
      assaying frequency and size of the mwh mosaic spots. To illustrate the use of the
      mwh(+)Y loss system, the effects of four known mutagens (X-rays, colchicine,
      ethyl methanesulfonate, and formaldehyde) and two genetic conditions (loss- and
      gain-of-function lodestar mutant alleles) are documented. The procedure is
      simple, sensitive, and inexpensive.

PMID- 22973548
TI  - Mitochondrial genome evolution in a single protoploid yeast species.
AB  - Mitochondria are organelles, which play a key role in some essential functions,
      including respiration, metabolite biosynthesis, ion homeostasis, and apoptosis.
      The vast numbers of mitochondrial DNA (mtDNA) sequences of various yeast species,
      which have recently been published, have also helped to elucidate the structural
      diversity of these genomes. Although a large corpus of data are now available on
      the diversity of yeast species, little is known so far about the mtDNA diversity
      in single yeast species. To study the genetic variations occurring in the mtDNA
      of wild yeast isolates, we performed a genome-wide polymorphism survey on the
      mtDNA of 18 Lachancea kluyveri (formerly Saccharomyces kluyveri) strains. We
      determined the complete mt genome sequences of strains isolated from various
      geographical locations (in North America, Asia, and Europe) and ecological niches
      (Drosophila, tree exudates, soil). The mt genome of the NCYC 543 reference strain
      is 51,525 bp long. It contains the same core of genes as Lachancea
      thermotolerans, the nearest relative to L. kluyveri. To explore the mt genome
      variations in a single yeast species, we compared the mtDNAs of the 18 isolates.
      The phylogeny and population structure of L. kluyveri provide clear-cut evidence
      for the existence of well-defined geographically isolated lineages. Although
      these genomes are completely syntenic, their size and the intron content were
      found to vary among the isolates studied. These genomes are highly polymorphic,
      showing an average diversity of 28.5 SNPs/kb and 6.6 indels/kb. Analysis of the
      SNP and indel patterns showed the existence of a particularly high overall level
      of polymorphism in the intergenic regions. The dN/dS ratios obtained are
      consistent with purifying selection in all these genes, with the noteworthy
      exception of the VAR1 gene, which gave a very high ratio. These data suggest that
      the intergenic regions have evolved very fast in yeast mitochondrial genomes.

PMID- 22973549
TI  - Genetic architecture of migration-related traits in rainbow and steelhead trout,
      Oncorhynchus mykiss.
AB  - Although migration plays a critical role in the evolution and diversification of
      species, relatively little is known of the genetic architecture underlying this
      life history in any species. Rainbow and steelhead trout (Oncorhynchus mykiss)
      naturally segregate for both resident and migratory life-history types,
      respectively, as do other members of the salmonid family of fishes. Using an
      experimental cross derived from wild resident rainbow and wild migratory
      steelhead trout from Southeast Alaska and high throughput restriction-site
      associated DNA (RAD) tag sequencing, we perform a quantitative trait locus (QTL)
      analysis to identify the number, position, and relative contribution of genetic
      effects on a suite of 27 physiological and morphological traits associated with
      the migratory life history in this species. In total, 37 QTL are localized to 19
      unique QTL positions, explaining 4-13.63% of the variation for 19 of the 27
      migration-related traits measured. Two chromosomal positions, one on chromosome
      Omy12 and the other on Omy14 each harbor 7 QTL for migration-related traits,
      suggesting that these regions could harbor master genetic controls for the
      migratory life-history tactic in this species. Another QTL region on Omy5 has
      been implicated in several studies of adaptive life histories within this species
      and could represent another important locus underlying the migratory life
      history. We also evaluate whether loci identified in this out-crossed QTL study
      colocalize to genomic positions previously identified for associations with
      migration-related traits in a doubled haploid mapping family.

PMID- 22973550
TI  - Hog1 controls global reallocation of RNA Pol II upon osmotic shock in
      Saccharomyces cerevisiae.
AB  - When challenged with osmotic shock, Saccharomyces cerevisiae induces hundreds of
      genes, despite a concurrent reduction in overall transcriptional capacity. The
      stress-responsive MAP kinase Hog1 activates expression of specific genes through
      interactions with chromatin remodeling enzymes, transcription factors, and RNA
      polymerase II. However, it is not clear whether Hog1 is involved more globally in
      modulating the cell's transcriptional program during stress, in addition to
      activating specific genes. Here we show that large-scale redistribution of RNA
      Pol II from housekeeping to stress genes requires Hog1. We demonstrate that
      decreased RNA Pol II occupancy is the default outcome for highly expressed genes
      upon stress and that Hog1 is partially required for this effect. We find that
      Hog1 and RNA Pol II colocalize to open reading frames that bypass global
      transcriptional repression. These activation targets are specified by promoter
      binding of two osmotic stress-responsive transcription factors. The combination
      of reduced global transcription with a gene-specific override mechanism allows
      cells to rapidly switch their transcriptional program in response to stress.

PMID- 22973551
TI  - In the field: exploiting the untapped potential of immunogenic modulation by
      radiation in combination with immunotherapy for the treatment of cancer.
AB  - Radiation has long been the standard of care for many types of cancer. It is
      employed to locally eradicate tumor cells as well as alter tumor stroma with
      either curative or palliative intent. Radiation-induced cell damage is an
      immunologically active process in which danger signals are released that
      stimulate immune cells to phagocytose and present locally released tumor
      associated antigens (TAAs). Recent studies have indicated that radiotherapy can
      also alter the phenotype of cancer cells that remain after treatment. These cells
      upregulate TAAs as well as markers, including major histocompatibility complex
      and costimulatory molecules, that make them much more immunostimulatory. As our
      understanding of the immunomodulatory effects of radiation has improved, interest
      in combining this type of therapy with immune-based therapies for the treatment
      of cancer has grown. Therapeutic cancer vaccines have been shown to initiate the
      dynamic process of host immune system activation, culminating in the recognition
      of host cancer cells as foreign. The environment created after radiotherapy can
      be exploited by active therapeutic cancer vaccines in order to achieve further,
      more robust immune system activation. This review highlights preclinical studies
      that have examined the alteration of the tumor microenvironment with regard to
      immunostimulatory molecules following different types of radiotherapy, including
      external beam radiation, radiolabeled monoclonal antibodies, bone-seeking
      radionuclides, and brachytherapy. We also emphasize how combination therapy with
      a cancer vaccine can exploit these changes to achieve improved therapeutic
      benefit. Lastly, we describe how these laboratory findings are translating into
      clinical benefit for patients undergoing combined radiotherapy and cancer
      vaccination.

PMID- 22973553
TI  - Acetylation Increases EWS-FLI1 DNA Binding and Transcriptional Activity.
AB  - Ewing Sarcoma (ES) is associated with a balanced chromosomal translocation that
      in most cases leads to the expression of the oncogenic fusion protein and
      transcription factor EWS-FLI1. EWS-FLI1 has been shown to be crucial for ES cell
      survival and tumor growth. However, its regulation is still enigmatic. To date,
      no functionally significant post-translational modifications of EWS-FLI1 have
      been shown. Since ES are sensitive to histone deacetylase inhibitors (HDI), and
      these inhibitors are advancing in clinical trials, we sought to identify if EWS
      FLI1 is directly acetylated. We convincingly show acetylation of the C-terminal
      FLI1 (FLI1-CTD) domain, which is the DNA binding domain of EWS-FLI1. In vitro
      acetylation studies showed that acetylated FLI1-CTD has higher DNA binding
      activity than the non-acetylated protein. Over-expression of PCAF or treatment
      with HDI increased the transcriptional activity of EWS-FLI1, when co-expressed in
      Cos7 cells. However, our data that evaluates the acetylation of full-length EWS
      FLI1 in ES cells remains unclear, despite creating acetylation specific
      antibodies to four potential acetylation sites. We conclude that EWS-FLI1 may
      either gain access to chromatin as a result of histone acetylation or undergo
      regulation by direct acetylation. These data should be considered when patients
      are treated with HDAC inhibitors. Further investigation of this phenomenon will
      reveal if this potential acetylation has an impact on tumor response.

PMID- 22973552
TI  - The contemporary role of renal mass biopsy in the management of small renal
      tumors.
AB  - The selective use of percutaneous biopsy for diagnosis in renal masses is a
      relatively uncommon approach when compared to the management of other solid
      neoplasms. With recent advancements in imaging techniques and their widespread
      use, the incidental discovery of asymptomatic, small renal masses (SRM) is on the
      rise and a substantial percentage of these SRM are benign. Recent advances in
      diagnostics have significantly improved accuracy rates of renal mass biopsy
      (RMB), making it a potentially powerful tool in the management of SRM. In this
      review, we will discuss the current management of SRM, problems with the
      traditional view of RMB, improvements in the diagnostic power of RMB, cost
      effectiveness of RMB, and risks associated with RMB. RMB may offer important
      information enabling treating clinicians to better risk-stratify patients and
      ultimately provide a more personalized treatment approach for SRM.

PMID- 22973554
TI  - Development of coagulation factor probes for the identification of procoagulant
      circulating tumor cells.
AB  - Metastatic cancer is associated with a hypercoagulable state, and pathological
      venous thromboembolic disease is a significant source of morbidity and the second
      leading cause of death in patients with cancer. Here we aimed to develop a novel
      labeling strategy to detect and quantify procoagulant circulating tumor cells
      (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration
      of procoagulant CTCs may be prognostic for the development of venous thrombosis
      in patients with cancer. Our approach is based on the observation that cancer
      cells are capable of initiating and facilitating cell-mediated coagulation in
      vitro, whereby activated coagulation factor complexes assemble upon cancer cell
      membrane surfaces. Binding of fluorescently labeled, active site-inhibited
      coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line,
      MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal
      cell line, SW620, was characterized in a purified system, in anticoagulated blood
      and plasma, and in plasma under conditions of coagulation. We conclude that a CTC
      labeling strategy that utilizes coagulation factor-based fluorescent probes may
      provide a functional assessment of the procoagulant potential of CTCs, and that
      this strategy is amenable to current CTC detection platforms.

PMID- 22973555
TI  - MAP17, a ROS-dependent oncogene.
AB  - MAP17 is a small 17 kDa non-glycosylated membrane protein previously identified
      as being overexpressed in carcinomas. Breast tumor cells that overexpress MAP17
      show an increased tumoral phenotype with enhanced proliferative capabilities both
      in the presence or the absence of contact inhibition, decreased apoptotic
      sensitivity, and increased migration. MAP17-expressing clones also grow better in
      nude mice. The increased malignant cell behavior induced by MAP17 is associated
      with an increase in reactive oxygen species (ROS) production, and the treatment
      of MAP17-expressing cells with antioxidants results in a reduction in the
      tumorigenic properties of these cells. The MAP17-dependent increase in ROS and
      tumorigenesis relies on its PDZ-binding domain because disruption of this
      sequence by point mutations abolishes the ability of MAP17 to enhance ROS
      production and tumorigenesis. MAP17 is overexpressed in a great variety of human
      carcinomas, including breast tumors. Immunohistochemical analysis of MAP17 during
      cancer progression demonstrates that overexpression of the protein strongly
      correlates with tumoral progression. Generalized MAP17 overexpression in human
      carcinomas indicates that MAP17 can be a good marker for tumorigenesis and,
      especially, for malignant progression.

PMID- 22973556
TI  - AZT as a telomerase inhibitor.
AB  - Telomerase is a highly specialized reverse transcriptase (RT) and the maintenance
      of telomeric length is determined by this specific enzyme. The human holoenzyme
      telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA
      component, hTR, and a group of associated proteins. Telomerase is normally
      expressed in embryonic cells and is repressed during adulthood. The enzyme is
      reexpressed in around 85% of solid tumors. This observation makes it a potential
      target for developing drugs that could be developed for therapeutic purposes. The
      identification of the hTERT as a functional catalytic RT prompted studies of
      inhibiting telomerase with the HIV RT inhibitor azidothymidine (AZT). Previously,
      we have demonstrated that AZT binds preferentially to telomeres, inhibits
      telomerase and enhances tumor cell senescence, and apoptosis after AZT treatment
      in breast mammary adenocarcinoma cells. Since then, several studies have
      considered AZT for telomerase inhibition and have led to potential clinical
      strategies for anticancer therapy. This review covers present thinking of the
      inhibition of telomerase by AZT and future treatment protocols using the drug.

PMID- 22973557
TI  - Do circulating tumor cells play a role in coagulation and thrombosis?
AB  - Cancer induces a hypercoagulable state, and patients with cancer who suffer a
      thrombotic event have a worse prognosis than those who do not. Recurrent
      pathologic thrombi in patients with cancer are clinically managed with
      anticoagulant medications; however, anticoagulant prophylaxis is not routinely
      prescribed owing to a complex variety of patient and diagnosis related factors.
      Early identification of patients at risk for cancer-associated thrombosis would
      allow for personalization of anticoagulant prophylaxis and likely reduce
      morbidity and mortality for many cancers. The environment in which a thrombosis
      develops in a patient with cancer is complex and unique from patients without
      cancer, which creates therapeutic challenges but may also provide targets for the
      development of clinical assays in this context. Circulating tumor cells (CTCs)
      may play a role in the association between cancer and thrombosis. Cancer
      metastasis, the leading cause of cancer-related deaths, is facilitated by the
      hematogenous spread of CTCs, and CTCs accompany metastatic disease across all
      major types of carcinomas. The role of CTCs in the pathogenesis of thrombosis has
      not been studied due to the previous difficulty in identifying these rare cells,
      but the interaction between these circulating cells and the coagulation system is
      an area of study that demands attention. The development of CTC detection
      platforms presents a new tool by which to characterize the role for CTCs in
      cancer-related hypercoagulability. In addition, this area of study presents a new
      avenue for assessing the risk of cancer-associated thrombosis and represents a
      potential tool for predicting which patients may benefit from anticoagulant
      prophylaxis. In this review, we will discuss the evidence in support of CTC
      induced hypercoagulability, and highlight areas where CTC-detection platforms may
      provide prognostic insight into the risk of developing thrombosis for patients
      with cancer.

PMID- 22973558
TI  - Dying cell clearance and its impact on the outcome of tumor radiotherapy.
AB  - The induction of tumor cell death is one of the major goals of radiotherapy and
      has been considered to be the central determinant of its therapeutic outcome for
      a long time. However, accumulating evidence suggests that the success of
      radiotherapy does not only derive from direct cytotoxic effects on the tumor
      cells alone, but instead might also depend - at least in part - on innate as well
      as adaptive immune responses, which can particularly target tumor cells that
      survive local irradiation. The clearance of dying tumor cells by phagocytic cells
      of the innate immune system represents a crucial step in this scenario. Dendritic
      cells and macrophages, which engulf, process and present dying tumor cell
      material to adaptive immune cells, can trigger, skew, or inhibit adaptive immune
      responses, respectively. In this review we summarize the current knowledge of
      different forms of cell death induced by ionizing radiation, the multi-step
      process of dying cell clearance, and its immunological consequences with special
      regard toward the potential exploitation of these mechanisms for the improvement
      of tumor radiotherapy.

PMID- 22973559
TI  - Rhizome of life, catastrophes, sequence exchanges, gene creations, and giant
      viruses: how microbial genomics challenges Darwin.
AB  - Darwin's theory about the evolution of species has been the object of
      considerable dispute. In this review, we have described seven key principles in
      Darwin's book The Origin of Species and tried to present how genomics challenge
      each of these concepts and improve our knowledge about evolution. Darwin believed
      that species evolution consists on a positive directional selection ensuring the
      "survival of the fittest." The most developed state of the species is
      characterized by increasing complexity. Darwin proposed the theory of "descent
      with modification" according to which all species evolve from a single common
      ancestor through a gradual process of small modification of their vertical
      inheritance. Finally, the process of evolution can be depicted in the form of a
      tree. However, microbial genomics showed that evolution is better described as
      the "biological changes over time." The mode of change is not unidirectional and
      does not necessarily favors advantageous mutations to increase fitness it is
      rather subject to random selection as a result of catastrophic stochastic
      processes. Complexity is not necessarily the completion of development: several
      complex organisms have gone extinct and many microbes including bacteria with
      intracellular lifestyle have streamlined highly effective genomes. Genomes evolve
      through large events of gene deletions, duplications, insertions, and genomes
      rearrangements rather than a gradual adaptative process. Genomes are dynamic and
      chimeric entities with gene repertoires that result from vertical and horizontal
      acquisitions as well as de novo gene creation. The chimeric character of
      microbial genomes excludes the possibility of finding a single common ancestor
      for all the genes recorded currently. Genomes are collections of genes with
      different evolutionary histories that cannot be represented by a single tree of
      life (TOL). A forest, a network or a rhizome of life may be more accurate to
      represent evolutionary relationships among species.

PMID- 22973561
TI  - The genetic integrity of bacterial species: the core genome and the accessory
      genome, two different stories.
AB  - Strains within a bacterial species typically have a set of conserved core genes
      and a variable set of accessory genes. The accessory genes often appear to move
      laterally between strains, thereby forming new trait combinations. Sometimes,
      genetic material also moves laterally between species, thereby resulting in
      diffuse borders between them. The growing number of genome sequences offers new
      possibilities to study these processes. Ten species for which abundant genomic
      data exists were here selected for analysis of the species border integrity. The
      average core genome similarities and relative core genome sizes (RCGSs) were
      determined for strain pairs within the species and for strain pairs crossing the
      species border. The variability within the species as well as the border
      integrity varies for different bacterial species. Some have very distinct borders
      while others are more or less indefinable. From the growing amount of genomic
      data, it becomes even clearer that the concept of bacterial species is, in many
      cases, far from absolute.

PMID- 22973560
TI  - Toll-like receptors are critical for clearance of Brucella and play different
      roles in development of adaptive immunity following aerosol challenge in mice.
AB  - Brucella spp. cause undulant fever in humans and brucellosis in variety of other
      animals. Both innate and adaptive immunity have been shown to be important in
      controlling Brucella infection. Toll-like receptors (TLRs) represent a group of
      pattern recognition receptors (PRRs) that play critical roles in the host innate
      immune response, as well as development of adaptive immunity. In the current
      report, we investigated the role of TLR signaling in the clearance of Brucella
      and development of adaptive immunity in TLR2(-/-), TLR4(-/-), or MyD88(-/-) mice
      following aerosol exposure to B. melitensis 16 M. Consistent with previous
      reports, MyD88 is required for efficient clearance of Brucella from all three
      organs (lung, spleen, and liver). The results reveal Th2-skewed immune responses
      in TLR2(-/-) mice late in infection and support a TLR2 requirement for efficient
      clearance of Brucella from the lungs, but not from the spleen or liver.
      Similarly, TLR4 is required for efficient clearance of Brucella from the lung,
      but exhibits a minor contribution to clearance from the spleen and no
      demonstrable contribution to clearance from the liver. Lymphocyte proliferation
      assays suggest that the TLRs are not involved in the development of cell-mediated
      memory response to Brucella antigen. Antibody detection reveals that TLR2 and 4
      are required to generate early antigen-specific IgG, but not during the late
      stages of infection. TLR2 and 4 are only transiently required for IgM production
      and not at all for IgA production. In contrast, MyD88 is essential for antigen
      specific IgG production late in infection, but is not required for IgM generation
      over the course of infection. Surprisingly, despite the prominent role for MyD88
      in clearance from all tissues, MyD88-knockout mice express significantly higher
      levels of serum IgA. These results confirm the important role of MyD88 in
      controlling infection in the spleen while providing evidence of a prominent
      contribution to protection in other tissues. In addition, although TLR4 and TLR2
      contribute little to control of spleen infection, a significant contribution to
      clearance of lung infection is described.

PMID- 22973563
TI  - The Canadian Society for Circumpolar Health is pleased to have played a role in
      facilitating this special issue on participatory methods in northern regions.
      Foreword.

PMID- 22973564
TI  - Addressing challenges in participatory research partnerships in the North:
      opening a conversation.

PMID- 22973562
TI  - Pharmaceutical aerosols for the treatment and prevention of tuberculosis.
AB  - Historically, pharmaceutical aerosols have been employed for the treatment of
      obstructive airway diseases, such as asthma and chronic obstructive pulmonary
      disease, but in the past decades their use has been expanded to treat lung
      infections associated with cystic fibrosis and other respiratory diseases.
      Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the
      bacilli from the cough of infected individuals. Even though TB affects other
      organs, the lungs are the primary site of infection, which makes the pulmonary
      route an ideal alternative route to administer vaccines or drug treatments.
      Optimization of formulations and delivery systems for anti-TB vaccines and drugs,
      as well as the proper selection of the animal model to evaluate those is of
      paramount importance if novel vaccines or drug treatments are to be successful.
      Pharmaceutical aerosols for patient use are generated from metered dose inhalers,
      nebulizers, and dry powder inhalers (DPIs). In addition to the advantages of
      providing more efficient delivery of the drug, low cost, and portability,
      pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage
      forms and do not require refrigeration. Methods to manufacture dry powders in
      respirable sizes include micronization, spray drying, and other proprietary
      technologies. Inhalable dry powders are characterized in terms of their drug
      content, particle size, and dispersibility to ensure deposition in the
      appropriate lung region and effective aerosolization from the device. These
      methods will be illustrated as they were applied for the manufacture and
      characterization of powders containing anti-tubercular agents and vaccines for
      pulmonary administration. The influence of formulation, selection of animal
      model, method of aerosol generation, and administration on the efficacy
      demonstrated in a given study will be illustrated by the evaluation of
      pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by our
      group.

PMID- 22973565
TI  - The health of Inuit children under age 6 in Canada.
AB  - OBJECTIVES: Previous research has suggested that Inuit children experience poor
      health as compared to their non-Aboriginal counterparts, although social
      determinants such as family and social conditions, lifestyle or behaviour, and
      cultural factors may be at play. The purpose of the current study was to examine
      the parent-reported health of Inuit children under 6 years of age living in
      Canada. STUDY DESIGN AND METHODS: Data from the 2006 Aboriginal Children's Survey
      were used to examine measures of Inuit child health as rated by parents including
      child health, limitations to physical activity, chronic conditions, ear
      infections, and dental problems. Associations between social determinants of
      health and parent-rated Inuit child health were also explored. RESULTS: Most
      Inuit children under age 6 were reported by their parents or guardians to be in
      excellent or very good health. The most common chronic conditions identified were
      asthma, speech and language difficulties, allergies, lactose intolerance, and
      hearing impairment. Several social determinants of health were associated with
      child health, including parental education, household income, breastfeeding, and
      perceived housing conditions. CONCLUSIONS: The findings show that social
      determinants of health, including both socio-economic and household
      characteristics, are associated with Inuit child health.

PMID- 22973567
TI  - Reply to W.B. Grant 'Re: Vitamin D deficiency among northern Native Peoples'.

PMID- 22973566
TI  - Temporal trends in Inuit, First Nations and non-Aboriginal birth outcomes in
      rural and northern Quebec.
AB  - OBJECTIVES: The objective was to assess trends in Inuit, First Nations and non
      Aboriginal birth outcomes in the rural and northern regions of Quebec. STUDY
      DESIGN AND METHODS: In a birth cohort-based study of all births to residents of
      rural and northern Quebec from 1991 through 2000 (n = 177,193), we analyzed birth
      outcomes and infant mortality for births classified by maternal mother tongue
      (Inuit, First Nations or non-Aboriginal) and by community type (predominantly
      First Nations, Inuit or non-Aboriginal). RESULTS: From 1991-1995 to 1996-2000,
      there was a trend of increasing rates of preterm birth for all 6 study groups. In
      all rural and northern areas, low birth weight rates increased significantly only
      for the Inuit mother tongue group [RR1.45 (95% CI 1.05-2.01)]. Stillbirth rates
      showed a non-significant increase for the Inuit mother tongue group [RR1.76 (0.64
      4.83)]. Neonatal mortality rates decreased significantly in the predominantly non
      Aboriginal communities and in the non-Aboriginal mother tongue group [RR0.78
      (0.66-0.92)], and increased non-significantly for the First Nations mother tongue
      group [RR2.17 (0.71-6.62)]. Perinatal death rates increased for the First Nations
      mother tongue grouping in northern areas [RR2.19 (0.99-4.85)]. CONCLUSION: There
      was a disconcerting rise of some mortality outcomes for births to First Nations
      and Inuit mother tongue women and to women in predominantly First Nations and
      Inuit communities, in contrast to some improvements for births to non-Aboriginal
      mother tongue women and to women in predominantly non-Aboriginal communities in
      rural or northern Quebec, indicating a need for improving perinatal and neonatal
      health for Aboriginal populations in rural and northern regions.

PMID- 22973568
TI  - Poor self-reported health and its association with biomarkers among Canadian
      Inuit.
AB  - OBJECTIVES: To determine the extent to which demographic characteristics,
      clinical measurements and biomarkers were associated with poor self-reported
      health (SRH) among Inuit adults in the Canadian Arctic. STUDY DESIGN: Cross
      sectional survey was adopted as the study design. METHODS: The International
      Polar Year Inuit Health Survey carried out in 36 Canadian Arctic communities in
      2007 and 2008 included Inuit men and women, aged 18 years or older, recruited
      from randomly selected households. The main outcome measure was SRH, which was
      dichotomized into good health (excellent, very good and good responses) and poor
      health (fair and poor responses). RESULTS: Of the 2,796 eligible households,
      1,901 (68%) households and 2,595 participants took part in the survey. The
      weighted prevalence of poor SRH was 27.8%. Increasing age was significantly
      associated with poor SRH. The relative risk ratios for poor SRH was 2.0 (95%
      confidence interval [CI] 1.3-3.1) for men aged 50 years or older and 2.3 (95% CI
      1.7-3.0) for women aged 50 years or older, compared with men and women aged 29
      years or younger. After adjusting for age, gender and body mass index, poor SRH
      was significantly associated with smoking status (odds ratio [OR]=1.5; CI 1.1
      2.0), at-risk fasting glucose levels (>= 6.1 mmol/L) (OR=2.5; 95%; CI 1.5-4.2)
      and elevated hs C-reactive protein levels (>3-<= 10 mg/L) (OR=2.1; 95% CI 1.4
      3.1). Poor SRH was also significantly associated with a hypertriglyceridemic
      waist phenotype (high-risk waist circumference >= 102 cm for men and >= 88 cm for
      women with high triglyceride levels, >= 1.7 mmol/L), adjusted for age and gender,
      OR=1.6; 95% CI 1.1-2.3. CONCLUSIONS: Clinically relevant indicators of chronic
      disease risk were related to subjective assessment of SRH among Inuit.

PMID- 22973569
TI  - A research review: exploring the health of Canada's Aboriginal youth.
AB  - OBJECTIVE: To compare the current state of health research on Aboriginal and non
      Aboriginal youth in Canada. DESIGN: A search of published academic literature on
      Canadian Aboriginal youth health, including a comprehensive review of both non
      Aboriginal and Aboriginal youth research, was conducted using MEDLINE and
      summarized. METHODOLOGY: A MEDLINE search was conducted for articles published
      over a 10-year period (2000-2010). The search was limited to research articles
      pertaining to Canadian youth, using various synonyms for "Canada," "youth," and
      "Aboriginal." Each article was coded according to 4 broad categories: Aboriginal
      identity, geographic location, research topic (health determinants, health
      status, health care), and the 12 key determinants of health proposed by the
      Public Health Agency of Canada (PHAC). RESULTS: Of the 117 articles reviewed,
      only 34 pertained to Aboriginal youth, while the remaining 83 pertained to non
      Aboriginal youth. The results revealed major discrepancies within the current
      body of research with respect to the geographic representation of Aboriginal
      youth, with several provinces missing from the literature, including the northern
      territories. Furthermore, the current research is not reflective of the
      demographic composition of Aboriginal youth, with an under-representation of
      Metis and urban Aboriginal youth. Health status of Aboriginal youth has received
      the most attention, appearing in 79% of the studies reviewed compared with 57% of
      the non-Aboriginal studies. The number of studies that focus on health
      determinants and health care is comparable for both groups, with the former
      accounting for 62 and 64% and the latter comprising 26 and 19% of Aboriginal and
      non-Aboriginal studies, respectively. However, this review reveals several
      differences with respect to specific focus on health determinants between the two
      populations. In non-Aboriginal youth studies, all the 12 key determinants of
      health of PHAC are explored, whereas in Aboriginal youth studies the health
      profile remains incomplete and several key determinants and health indicators are
      neglected. CONCLUSIONS: The current studies are not reflective of the demographic
      and geographic profiles of Aboriginal youth in Canada, and they have also failed
      to provide a comprehensive examination of their unique health needs and concerns
      compared with studies on non-Aboriginal youth.

PMID- 22973571
TI  - Knowledge translation in Arctic environmental health.

PMID- 22973570
TI  - Victimisation and PTSD in a Greenlandic youth sample.
AB  - BACKGROUND: Despite a growing number of studies and reports indicating a very
      high and increasing prevalence of trauma exposure in Greenlandic adolescents, the
      knowledge on this subject is still very limited. The purpose of the present study
      was twofold: To estimate the lifetime prevalence of potentially traumatic events
      (PTEs) and post-traumatic stress disorder (PTSD) and to examine the relationship
      between PTEs, estimated PTSD, and sociodemographic variables. METHODS: In a
      Greenlandic sample from 4 different schools in 2 different minor towns in
      Northern Greenland, 269 students, aged 12-18 (M=15.4; SD=1.84) were assessed for
      their level of exposure to 20 PTEs along with the psychological impact of these
      events. RESULTS: Of the Greenlandic students, 86% had been directly exposed to at
      least 1 PTE and 74.3% had been indirectly exposed to at least 1 PTE. The mean
      number of directly experienced PTEs was 2.8 and the mean number of indirectly
      experienced PTEs was 3.9. The most frequent direct events recorded were death of
      someone close, near drowning, threat of assault/beating, humiliation or
      persecution by others and attempted suicide. The estimated lifetime prevalence of
      PTSD was 17.1%, whereas another 14.2% reached a subclinical level of PTSD
      (missing the full diagnosis by 1 symptom). Education level of the father, and
      being exposed to multiple direct and indirect PTEs were significantly associated
      with an increase in PTSD symptoms. CONCLUSION: The findings indicate substantial
      mental health problems in Greenlandic adolescents and that these are associated
      with various types of PTEs. Furthermore, the findings indicate that Greenlandic
      adolescents are more exposed to certain specific PTEs than adolescents in similar
      studies from other nations. The present study revealed that Greenlandic girls are
      particularly vulnerable towards experiencing PTEs. Indeed, in general, girls
      reported more experiences of direct and indirect PTEs. Furthermore, girls
      reported being more commonly exposed to specific types of PTEs compared to boys.

PMID- 22973572
TI  - Modeling and design of micromachined optical Soller collimators for lensless CCD
      based fluorometry.
AB  - To address the needs of medical diagnostics in resource-poor settings, it is
      necessary to develop low cost, simple and portable Point of Care detectors for
      integrated medical diagnostics. Previously, we have described a simple lensless
      fluorometer with sensitivity in the range of current ELISA plate readers. The key
      to the lensfree fluorometer is the uniform spatial distribution of light, which
      we achieved using a simple optical collimator based on a "stack of pinholes" (a
      stack of black PMMA plates with arrays of pinholes machined via laser) enabling
      the light to be collimated from the LED light source through the necessary
      wavelength filters and the assay's microfluidics directly onto the CCD without a
      lens. In this paper, we describe the optical principle for designing these Soller
      collimators for lensfree CCD-based fluorometry. The illuminating surface was
      modeled as a collection of differential areas emitting uniformly and spherically,
      and the intensity contribution of each emitting area was summed over the detector
      surface. To compute the final light intensity distribution from such a
      differential model we derived an integral equation to sum the individual
      intensity contributions from the two-dimensional emitting surface. The equation
      is for a single-hole collimator. Light intensity measurements were taken by
      placing a collimator with a particular aspect ratio (the ratio of hole length to
      diameter (L/d)) over the CCD image sensor and capturing an image. The resulting
      image is the 2D light intensity profile generated by the collimator. As the
      aspect ratio is increased the slope of the light intensity profile increases,
      corresponding to an increased degree of collimation. To test the model, the
      measured maximum and mean light intensities were compared with the theoretical
      predictions generated from the model. There was an agreement between the
      variation of the mean (R(2) = 0.990) and maximum (R(2) = 0.938) values of light
      intensities with aspect ratios based modeling. These profile measurements suggest
      an excellent agreement with the theoretical predictions. The integral equation
      presented here can be used to perfect the design of the optical Soller
      collimator. These results may lead to the development of more effective Soller
      collimators for lensfree CCD-based fluorometry for use in simple low cost
      lensfree optical detectors with the potential to enhance the accessibility and
      the quality of health care for underserved populations.

PMID- 22973573
TI  - Structural characterization of synthetic polymers using thermal-assisted
      atmospheric pressure glow discharge mass spectrometry.
AB  - With the development of material science and the practical needs of the polymer
      industry, rapid characterization of synthetic polymers using mass spectrometry is
      of sustainable interest. Herein a new method for characterizing synthetic
      polymers using thermal-assisted atmospheric pressure glow discharge mass
      spectrometry (TA-APGD-MS) is established. After illustration of the mechanism of
      ion formation, typical polymer samples such as polystyrene (PS), polyoxymethylene
      (POM) and poly (butanediol succinate) (PBS) were directly characterized at the
      molecular level using TA-APGD-MS. The thermal degradation products of synthetic
      polymers including monomer units and/or other fragments were rapidly detected by
      tandem mass spectrometry, providing rich information about the chemical
      composition for the structural characterization of homo- and co-polymers. The
      result suggests that TA-APGD-MS allows direct and rapid analysis of both
      synthetic homo-polymers and co-polymers under ambient conditions without any
      sample pretreatment. This method features high throughput, high sensitivity and
      rich information, showing promising applications in polymer science.

PMID- 22973574
TI  - Polarised phosphorescent emission in an organoplatinum(II)-based liquid
      crystalline polymer.
AB  - By combination of mesogenic rod-like cycloplatinated monomers based on 2,5-di(4
      alkenyloxyphenyl)pyridine ligands with 1,1,3,3,5,5-tetramethyltrisiloxane, a
      phosphorescent, liquid-crystalline polymer was obtained, which showed polarised
      emission.

PMID- 22973575
TI  - Unprecedented crystal dynamics: reversible cascades of single-crystal-to-single
      crystal transformations.
AB  - A series of Cu(II) complexes showed unprecedented reversible cascades of single
      crystal-to-single-crystal (SCSC) transformations, and more interestingly, very
      rapid crystal dynamic processes were observed in this system via the substitution
      of coordinating components without loss of single crystallinity.

PMID- 22973585
TI  - FDA approves first pacemaker system safe for magnetic resonance imaging. 
      Traditional cardiac devices have been at risk of malfunctioning or overheating
      with MRIs.

PMID- 22973586
TI  - Combination therapy often best approach to treat hypertension. Research shows
      that starting with two medications leads to healthier outcomes in the effort to
      control high blood pressure.

PMID- 22973587
TI  - Treat thyroid disease to help protect your heart.  Thyroid disease can sometimes
      cause heart palpitations, but even worse it can increase your risk of atrial
      fibrillation.

PMID- 22973588
TI  - Know how to respond if you have PAD and experience a "leg attack". Understand the
      symptoms that require immediate medical attention if you have peripheral arterial
      disease. Critical limb ischemia could lead to amputation.

PMID- 22973589
TI  - Wireless cardiac devices offer innovative aid to heart patients.  Advanced
      technology expected to usher in new paradigm shift promising to improve heart
      failure therapy and lower health care costs.

PMID- 22973590
TI  - Dabigatran emerges as safe and effective warfarin alternative. The recently
      approved drug is more expensive, but appears to be more predictable.

PMID- 22973591
TI  - Manage your diabetes with a heart-healthy diet.  Complex carbohydrates, whole
      grains, and fiber can help control your blood glucose levels and your weight.

PMID- 22973592
TI  - Does your heart need a multivitamin?  There's little evidence to suggest
      multivitamins help prevent heart disease.

PMID- 22973593
TI  - The miracle drug for women with heart failure may be testosterone. The hormone
      treatment may help patients recover some of the energy and strength lost because
      of their heart conditions.

PMID- 22973594
TI  - Women recover from aortic valve surgery more quickly than men.  Research shows
      that women's hearts shrink back to a healthier size after surgery at a faster
      rate than men's hearts after the same operation.

PMID- 22973595
TI  - I am a 65-year-old woman with a total cholesterol level of 233 mg/dL.  My HDL is
      78 mg/dL and my LDL is 137 mg/dL.  My doctor says I have hypercholesterolemia. 
      What do I need to do?

PMID- 22973596
TI  - I read that common over-the-counter pain medications increase the risk of heart
      attack and stroke. What can I take for my aching hands? I think I have arthritis,
      but it's not bad enough to see a rheumatologist yet.

PMID- 22973597
TI  - I am at high risk for heart attack and would like to try non-medical ways to
      lower my risk. What is meant by "aggressive lifestyle modification"?

PMID- 22973598
TI  - I heard that women with heart failure live longer than men with heart failure. 
      If this is true, can you tell me why?

PMID- 22973599
TI  - Persistent high heart rate raises mortality rate in CHD patients.  A high heart
      rate in patients with stable coronary heart disease raises the risk of
      complications even when other factors are under control.

PMID- 22973600
TI  - The health of your gums may affect the health of your heart. Regular dental care
      may reduce your risk of heart disease.

PMID- 22973601
TI  - Incision-free surgery to be next weight-loss breakthrough. Innovative procedure
      is expected to be approved in 2011.

PMID- 22973602
TI  - I was diagnosed with coronary artery disease about a year ago and have since had
      one stent put in.  I take my medications and try to live a healthy lifestyle with
      regular exercise and a good diet, but I frequently find myself worrying about my
      heart and life expectancy.  Any advice?

PMID- 22973603
TI  - I've heard that heart disease and kidney disease are related, but how exactly? Is
      it that kidney problems can cause heart problems in a person with a relatively
      healthy heart, or is it that heart disease can lead to kidney disease in someone
      with healthy kidneys?

PMID- 22973605
TI  - Abstracts of the 2011 Annual Scientific Meeting of the Israeli Society for
      Auditory Research (ISAR), October 25, 2011, Tel-Aviv, Israel.

PMID- 22973606
TI  - Proceedings of the 178th Falk Symposium, September 2-3, 2011, Cologne, Germany.

PMID- 22973607
TI  - Specifications for medical examinations of underground coal miners. Final rule.
AB  - This final rule modifies the Department of Health and Human Services (HHS)
      regulations for medical examinations of underground coal miners. Existing
      regulations established specifications for providing, interpreting, classifying,
      and submitting film-based roentgenograms (now commonly called chest radiographs
      or X-rays) of underground coal miners. The revised standards modify the
      requirements to permit the use of film-based radiography systems and add a
      parallel set of standards permitting the use of digital radiography systems. An
      additional amendment requires coal mine operators to provide the National
      Institute for Occupational Safety and Health (NIOSH) with employee rosters to
      assist the Coal Workers' Health Surveillance Program in improving participation
      by miners.

PMID- 22973608
TI  - Abstracts of the Royal Pharmaceutical Society (RPS) Annual Conference 2012.
      September 9-10, 2012. Birmingham, United Kingdom.

PMID- 22973609
TI  - Nathan Sharon: 1925-2011.

PMID- 22973610
TI  - Right-size; don't super-size.

PMID- 22973611
TI  - Part of the cure or part of the problem?

PMID- 22973612
TI  - Good design relates to all building types.

PMID- 22973613
TI  - Design and an excess of drama.

PMID- 22973604
TI  - Adherence in single-parent households in a long-term asthma clinical trial.
AB  - Adherence of participants in a long-term clinical trial is necessary to assure
      validity of findings. This article examines adherence differences between single
      parent and two-parent families in the Childhood Asthma Management Program (CAMP).
      Adherence was defined as the percentage of completed daily diary cards and
      scheduled study visits during the course of the trial. Logistic regression and
      ordinal logistic regression analyses were used. Children from single-parent
      families had a lower percentage of completed diary cards (72% vs. 84%) than two
      parent families. Single-parent families were also more likely to reschedule
      visits (62% vs. 45%) and miss more clinic visits (23% vs. 17%) than two-parent
      families. Suggestions are given for study coordinators to assist participants in
      completing a long-term clinical trial. Many suggestions may be adapted for nurses
      in inpatient or outpatient settings for assisting parents of patients with
      chronic diseases.

PMID- 22973614
TI  - Searching for evidence.
AB  - PURPOSE: There is a clear call for a single-source knowledge base linking
      literature on architecture and human outcomes. However, this seemingly simple
      need relies upon a vast source of information from multiple disciplines, each
      with their own vocabulary, structures, and modes of disciplinary thought.
      BACKGROUND: The "Information Age" provides an abundance of research from the
      sciences as well as the humanities. Despite unprecedented access via public and
      licensed databases, searching across knowledge repositories remains a labor
      intensive and skilled task. It therefore behooves the design profession to
      collaborate with experts in research, and to seek new skills for searching,
      interpreting, and applying evidence to design. METHODS: The pattern of database
      usage by 71 professionals involved with evidence-based design in healthcare
      facilities was studied. Respondents represented a range of interests including
      healthcare practitioners and executives, researchers, and design professionals.
      FINDINGS: Survey analysis revealed that a large number of information
      repositories are used (45), though few sources were used in common among the
      respondents.

PMID- 22973615
TI  - Places that evoke the human spirit.

PMID- 22973616
TI  - Islam and the healthcare environment: designing patient rooms.
AB  - Islam and the Muslim population are often the source of much misunderstanding and
      media-influenced misconceptions. Muslim patients who enter the healthcare
      environment are often weak and likely to experience feelings of vulnerability.
      Because of the complex and interwoven nature of culture and religion in a
      person's identity, it is important to consider patient belief systems and values
      when designing a patient's immediate environment. Through an exploration of
      literature related to culture and diversity and the beliefs and value system of
      the Muslim population, the authors were able to identify flexible design
      initiatives that could accommodate an array of cultural and spiritual practices.
      Islam and the Muslim population were chosen as the points of reference for this
      study because of the strong influence of the religion on the culture, and because
      of the many nuances that differ from the dominant culture within the United
      States. From these points of reference, a hypothetical design was developed for a
      patient room that considers differing notions of privacy, alternatives for
      cultural and religious practices, and ways to include symbolic meaning derived
      from attributes such as color.

PMID- 22973617
TI  - Establishing an acute care nursing bed unit size: employing a decision matrix
      framework.
AB  - Determining the number of patient rooms for an acute care (medical-surgical)
      patient unit is a challenge for both healthcare architects and hospital
      administrators when renovating or designing a new patient tower or wing.
      Discussions on unit bed size and its impact on hospital operations in healthcare
      design literature are isolated, and clearly there is opportunity for more
      extensive research. Finding the optimal solution for unit bed size involves many
      factors, including the dynamics of the site and existing structures. This opinion
      paper was developed using a "balanced scorecard" concept to provide decision
      makers a framework for assessing and choosing a customized solution during the
      early planning and conceptual design phases. The context of a healthcare balanced
      scorecard with the quadrants of quality, finance, provider outcomes, and patient
      outcomes is used to compare the impact of these variables on unit bed size.

PMID- 22973618
TI  - Hazards of intra-hospital transport (IHT).

PMID- 22973619
TI  - Congratulations on the publication of the Health Environments and Design Journal.

PMID- 22973620
TI  - The launch of HERD.

PMID- 22973621
TI  - Congratulations on the launch of HERD.

PMID- 22973622
TI  - Hospitals and healthcare.

PMID- 22973623
TI  - Emerging science of evidence-based design (EBD).

PMID- 22973624
TI  - Knowledge base of healthcare architecture.

PMID- 22973625
TI  - William J. Gies: a man of his word.

PMID- 22973626
TI  - Mouth bacteria. An essay presented to the Canadian Oral Prophylactic Association.
      1918.

PMID- 22973627
TI  - A dental school on university lines. 1916.

PMID- 22973628
TI  - Independent journalism versus trade journalism in dentistry: an irrepressible
      conflict. 1916.

PMID- 22973629
TI  - The Journal of Dental Research. 1919.

PMID- 22973630
TI  - Dental education in the United States and Canada. A report to the Carnegie
      Foundation for the advancement of teaching. 1926.

PMID- 22973631
TI  - Statutory definition and regulation of the practice of dentistry. 1926.

PMID- 22973632
TI  - General view and conclusions. A report to the Carnegie Foundation for the
      Advancement of Teaching. 1926.

PMID- 22973633
TI  - Response to tribute. 1937.

PMID- 22973634
TI  - Dental autonomy: a policy of isolation. 1942.

PMID- 22973635
TI  - Letters by William J. Gies. 1916-1940.

PMID- 22973636
TI  - "When nurses have respect, care is better".

PMID- 22973637
TI  - Shift patterns divide nursing.

PMID- 22973638
TI  - Nurses need new skills for NHS of the future.

PMID- 22973639
TI  - Drug workers need new skills to address rise in steroid use.

PMID- 22973640
TI  - "Rotate roles to ensure we treat both mental and physical health".

PMID- 22973641
TI  - "Many issues and beliefs affect individual sun safety advice".

PMID- 22973642
TI  - How nurses can use social media professionally.
AB  - Nurses can use social networking sites for professional development. This article
      provides advice on using social media professionally and ensuring this usean
      complies with the code of conduct.

PMID- 22973643
TI  - Strategy to reduce avoidable pressure ulcers.
AB  - Pressure ulcers have a detrimental effect on patient health and wellbeing and
      place a significant economic burden on the NHS. NHS Midlands and East, a cluster
      strategic health authority, has embarked on a programme of "ambitions" to ensure
      high-quality care and patient safety. The SHA identified the elimination of all
      grade 2, 3 and 4 pressure ulcers by December 2012 as its first ambition. This
      article discusses the methods chosen for measuring and monitoring the incidence
      and prevalence of pressure ulcers, and the nurse's role.

PMID- 22973644
TI  - Main types of skin cancer and treatment options.
AB  - This first in a two-part series on skin cancer gives an overview of the most
      common types and outlines the main treatment options. Part 2, to be published
      next week, discusses the causes of and risk factors for skin cancer, highlighting
      those people who are most at risk and the importance of early diagnosis.

PMID- 22973645
TI  - Managing pain in children with epidermolysis bullosa.
AB  - Epidermolysis bullosa is a rare genetic skin fragility disorder, with several
      types of varying severity. While research is progressing towards effective
      treatments, management remains symptomatic. One of the most distressing symptoms
      is pain, which may be multifactorial in origin. This article focuses on managing
      procedural pain during dressing changes and includes a case study.

PMID- 22973646
TI  - Making new lives welcome.

PMID- 22973647
TI  - Maintaining morale during the Olympics.

PMID- 22973648
TI  - Performance improvement and health cost reductions.

PMID- 22973650
TI  - Asthma & swimming: what's the verdict?

PMID- 22973649
TI  - To hydrate or not at the end of life.

PMID- 22973651
TI  - Changing trends in thyroidectomy.
AB  - The objective of this study was to establish the indications, referral trends and
      demographics for thyroidectomies performed in our institutions over a 13-year
      period by a single surgeon. We conducted a retrospective chart review of 1003
      consecutive thyroidectomies at our institutions during the period 1998 until
      2010. The parameters incorporated to this study were age, sex, county, referral
      source, symptoms, thyroid status, procedure performed, histopathology and post
      operative complications. The age range of patients was 4-87 years. There were 777
      females and 226 males, with a sex ratio of 3.4:1. The mean age was 51 years. The
      commonest indications for surgery were a potential or definite neoplastic thyroid
      mass (781 cases--78%), compressive symptoms (119 cases-- 12%), thyrotoxicosis and
      endocrine related causes (103 cases--10%). 896 (89.3%) patients were euthyroid, 4
      (0.4%) hypothyroid and 103 (10.3%) hyperthyroid. There were 739 partial
      thyroidectomies and 264 total thyroidectomies. Histopathology results showed that
      742 were benign and 261 malignant, of which papillary carcinomas accounted for
      75.1%, follicular carcinomas 13.4%, Hurthle cell carcinoma 1.5%, medullary
      thyroid carcinomas 3 %/, undifferentiated carcinomas 3%, others (lymphoma and
      squamous cell carcinomas) 4%. Post-operative complications were: Temporary
      hypocalcaemia--6.4%, Permanent hypocalcemia in--0.8%. Haemorrhage and seroma in
      1.5%, unilateral vocal cord paralysis in 1.2%/, post-operative wound infection in
      0.3% and pulmonary embolism in 0.01%. There was no mortality. Dublin accounted
      for 519 (51.7%/) of referrals, 484 (48.3%) was from the rest of the country.
      General practitioners accounted for 84.8%/ of referrals. Endocrine referrals
      comprised 9.8%. Other specialities constituted 5.4%. Two significant findings
      from this study were; firstly, a trend depicting increasing referral rates from
      the general practitioner and endocrine services. Secondly, low post-operative
      complication rates that compare favourably to published figures in previous
      studies from tertiary centres.

PMID- 22973652
TI  - Housecalls in general practice.
AB  - Home visits by General Practitioners have declined in many countries. We
      performed a study of home visits in an inner city practice in Dublin. We noted
      that rates of housecalls have declined at our practice in recent years from an
      average of 45 per month in 2006 to an average of 35 per month in 2010. We found
      that 88 (88%) of the recent housecalls we undertook had a valid medical or social
      indication in the opinion of the visiting GP. 21 housecalls (21%) were done for
      solely social reasons. The vast majority of our recent housecalls i.e. 91 (91%)
      were to patients who are entitled to free medical care under the General Medical
      Services scheme and 75 (75%) were to patients who were over 65 years of age. 87
      housecalls (87%) were to patients with multiple morbidities. With our ageing
      population it is likely that the housecall will not vanish from clinical
      practice.

PMID- 22973653
TI  - Radiological error--an early assessment of departmental radiology discrepancy
      meetings.
AB  - This study reviews cases discussed at radiology departmental discrepancy meetings
      and retrospectively determines patterns of radiological error. All cases
      discussed since the inception of our departmental discrepancy meetings (20-month
      period) were reviewed. Discrepancies were classified according to the RADPEER
      score. The imaging method from which the discrepancy arose was recorded. An
      attendance log at all meetings was kept. 111 discrepancies were identified in 104
      patients. 52 (46.85%) of the 111 discrepancies arose in relation to plain film
      radiography, 46 (41.44%) to CT, 11 (9.9%) to magnetic resonance imaging, and 2
      (1.8%) to nuclear medicine examinations. Several repeating discrepancies were
      identified. Discrepancy Meetings facilitate collective learning from radiology
      discrepancies and thereby improve patient safety. They provide radiologists with
      the invaluable opportunity to reconsider current practice and when indicated to
      change and improve practice. The majority of discrepancies are due to false
      negative interpretation and occur primarily in plain film and CT reporting.

PMID- 22973654
TI  - Paediatric umbilical cord blood transplantation.
AB  - Umbilical cord blood is being used increasingly as a source of haematopoietic
      stem cells for transplantation because of rapid availability, and the
      unavailability of a HLA matched adult donor for some patients. This study reports
      the characteristics and outcomes of 15 patients who have undergone umbilical cord
      blood transplantation (UCBT) in Ireland between 1998 and 2009. The median total
      nucleated cell and CD34+ doses post-processing were 6.5 x 107cells/kg and 1.8 x
      105 cells/kg, respectively. Median neutrophil recovery time was 30 days (range,
      14-44). Median platelet recovery time was 46.5 days (range, 35-148). 33.3% of
      patients developed acute cutaneous graft-versus-host disease (GVHD) grade I-II.
      Three patients died of transplant-related toxicity and two died of leukaemic
      relapse. We conclude that, with a satisfactory stem cell dose, UCBT offers a high
      chance of engraftment with acceptable toxicity, and should be regarded as a
      favourable option in selected patients when satisfactory bone marrow or
      peripheral blood stem cell donors are not available.

PMID- 22973655
TI  - Epidemiology and resistance patterns in urinary pathogens from long-term care
      facilities and GP populations.
AB  - Urinary tract infections (UTIs) are a major source of antimicrobial prescribing
      in the clinical setting and a potential reservoir for the emergence of resistant
      organisms. Although studies have been published on resistance rates for urinary
      pathogens from both hospital and general practitioner (GP) settings, there is
      little information from Long-Term Care Facilities (LTCFs) in Ireland. This study
      aimed to document the epidemiology and resistance rates in urinary isolates, in
      the LTCF and GP setting, from samples submitted to a typical microbiology
      laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary
      isolates from GPs, identified from patients 65 years and over, with cytology
      suggestive of infection. E. coil was the most common causative organism
      identified. There were significantly higher levels of resistance to ampicillin,
      co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and
      piperacillin/tazobactam in the LTCF population compared to the GP population
      (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v-
      4% respectively). Isolates with resistance mechanisms to beta-lactams, were
      identified in both populations. Results presented in this paper demonstrate
      significant differences between resistance rates in LTCF and GP populations which
      suggest that there are implications for empiric antimicrobial prescribing for
      UTIs in the LTCF setting.

PMID- 22973656
TI  - Fetal hydronephrosis: optimal renal pelvic measurement to increase detection rate
      for renal pathology.
AB  - We reviewed the outcome of fetal hydronephrosis with a renal pelvic dilatation
      (RPD) of 4-7 mm to assess whether a RPD > 7 mm had a higher predictive value for
      renal pathology. 373 fetuses were diagnosed with hydronephrosis giving an
      incidence of 2.2%. The male: female ratio was 1.8:1. 5(1.34%) fetuses with
      antenatal hydronephrosis were diagnosed with Down Syndrome. 299 (91.7% fetuses
      with an RPD of 4-7 mm had resolved by 34 weeks gestation with 10 (3.1%) having
      moderate to severe hydronephrosis. The resolution rate for RPD > 7 mm was 60.7%
      (17) with 11 fetuses (39.3%) requiring long term follow up.

PMID- 22973657
TI  - Drug induced aseptic meningitis caused by intravenous immunoglobulin therapy.
AB  - Drug induced aseptic meningitis (DIAM) is an uncommon condition that can mimic
      infective conditions. DIAM has been recognized with various treatments including
      non-steroidal anti-inflammatory drugs, monoclonal antibodies and some
      antibiotics. We report a patient presenting with aseptic meningitis forty-eight
      hours after commencing a course of intravenous immunoglobulin (IVIG) treatment.
      It is important that physicians prescribing this medication are aware of this
      rare complication so the diagnosis can be made quickly and the patient is not
      exposed to unnecessary treatments.

PMID- 22973658
TI  - A case of Lambert-Eaton myasthenic syndrome with possible myasthenia gravis.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of
      neuromuscular transmission (NMJ) that shares many clinical features with
      myasthenia gravis (MG). We report a 73 year-old lady who presented 10 years
      previously with stiffness of both calves, dry mouth, fatigue, proximal weakness
      and areflexia in lower limbs. Neurophysiological studies were consistent with
      LEMS. Her work up for an underlying neoplasm was negative. She recently developed
      unilateral ptosis and diplopia which dramatically improved with pyridostigmine
      suggesting concomitant MG.

PMID- 22973659
TI  - Giant parotid pleomorphic adenoma in parapharyngeal space causing severe
      obstructive sleep apnoea.
AB  - We report a case of a large pleomorphic adenoma arising from the deep lobe of the
      parotid gland in the parapharyngeal space and causing obstructive sleep apnoea.
      Review of literature, clinical features, pathology, radiological findings and
      treatment of these tumours are discussed.

PMID- 22973660
TI  - A patient with a rare leukodystrophy related to lamin B1 duplication.
AB  - The hereditary leukodystrophies are rare disorders caused by molecular
      abnormalities leading to destruction of or failure of development of central
      white matter. For almost 30 years there has been increasing recognition of later
      onset Autosomal Dominant Leukodystrophy (ADLD). We report the first genetically
      confirmed case of lamin B1 duplication causing ADLD from Ireland.

PMID- 22973661
TI  - Smoking & public transport.

PMID- 22973662
TI  - Storage of schedule 2 controlled drugs by general practitioners in the HSE West
      region.

PMID- 22973663
TI  - Vocal cord paralysis.

PMID- 22973664
TI  - Dosing errors with infant vitamin D3 supplements.

PMID- 22973665
TI  - Patient perceptions of the cardiology ward round.

PMID- 22973666
TI  - JFHC comes alive.

PMID- 22973667
TI  - "We need to talk about obesity".

PMID- 22973668
TI  - "The government needs to get tough and legislate".

PMID- 22973669
TI  - A topic in 10 questions. How to give feeding and nutrition support to new
      parents.

PMID- 22973670
TI  - The sun has got its hat on: How the warm weather can affect children's skin.

PMID- 22973671
TI  - The sunshine vitamin.

PMID- 22973672
TI  - Carry on camping.

PMID- 22973673
TI  - Improving access to hepatitis C care for urban, underserved patients using a
      primary care-based hepatitis C clinic.
AB  - OBJECTIVE: Chronic hepatitis C affects 200 million people worldwide and is a
      leading cause of death from liver disease. Effective treatment is available but
      can be difficult to access for uninsured, urban patients. National organizations
      have called for improving access to hepatitis C care in these groups. We present
      an innovative model for expanding access to hepatitis C care for urban,
      underserved patients (The Grady Liver Clinic, Grady Memorial Hospital, Atlanta,
      Georgia). The liver clinic provides hepatitis C care by general internists in the
      primary care setting. METHODS: We performed a retrospective chart review of all
      liver clinic patients (n=807) who presented in the first 5 years of the clinic's
      operation. Measures included patients' demographic and hepatitis C-related
      characteristics; prevalence of medical, psychiatric, and substance abuse
      comorbidities; and treatment status. RESULTS: The liver clinic population is
      primarily black (76%) and uninsured (59%). Patients had difficult-to-treat
      characteristics, including genotype 1 hepatitis C (90%), advanced liver fibrosis
      (28%), and high viral loads. Sixty-seven percent had comorbid medical conditions,
      and 40% had psychiatric disease. Fourteen percent of patients were treated for
      hepatitis C during the study period. CONCLUSION: The liver clinic has proven to
      be a successful model for improving access to hepatitis C care for urban,
      underserved patients. Despite having significant hepatic disease and medical and
      psychiatric comorbidities, patients in the liver clinic can be successfully
      maintained in care and initiated on hepatitis C treatment by general internists
      in a primary care setting.

PMID- 22973674
TI  - Evaluation of serotype-specific immunity to Streptococcus pneumoniae in pregnant
      women and cord blood of infants: impact of race and ethnicity.
AB  - BACKGROUND: Although invasive pneumococcal disease (IPD) has significantly
      decreased in children since the introduction of the pneumococcal conjugate
      vaccine, instances of IPD from non-PCV7 serotypes have increased. Concerns remain
      regarding the risk for IPD during the neonatal period. Our objective was to
      measure quantitative antibody levels to 16 serotypes of Streptococcus pneumoniae
      in pregnant non-Hispanic black, non-Hispanic white, and Hispanic mothers, and in
      cord blood samples. METHODS: Antibody levels were evaluated by Luminex assay.
      RESULTS: Forty-two percent of all mothers had protective (-0.35 microg/mL)
      antibody levels to 16 serotypes. Hispanic mothers were most likely to possess
      protective antibody levels for 12 serotypes but were less likely to possess
      protective antibody levels for serotypes 9V, 12F, and 18C, compared to non
      Hispanic white or black mothers. Thirty-three percent of cord blood samples
      demonstrated protective antibody levels. Hispanic infants had a higher prevalence
      of protective antibodies to all serotypes except 11A, 14, 18C, and 23F. Non
      Hispanic black infants had a higher prevalence of protective immunity to
      serotypes 11A, 14, and 18C, and non-Hispanic white infants to only serotype 23F.
      CONCLUSIONS: Hispanic mothers and their infants have a higher prevalence of
      protective immunity to most serotypes of S pneumoniae, compared to white or black
      mothers/infants. We found no evidence of a lower prevalence of protective
      immunity to specific serotypes in non-Hispanic black vs. non-Hispanic white
      infants that might account for the reported higher incidence of IPDs in blacks.
      Environmental factors in Hispanic mothers may be responsible for their enhanced
      level of immunity. A significant number of cord blood samples had inadequate
      levels of protective immunity to a variety of S pneumoniae serotypes.

PMID- 22973675
TI  - The impact of prenatal education on behavioral changes toward breast feeding and
      smoking cessation in a healthy start population.
AB  - PURPOSE: To evaluate the impact of prenatal education by case managers on 2
      social determinants of health behaviors-breast feeding and smoking cessation
      among participants enrolled in Indianapolis Healthy Start (IHS). METHOD: Birth
      and death data up to 1 year for IHS clients were collected from Marion County
      vital records for births 20 weeks or greater. Case managers provide education on
      the health benefits for mothers and infants on breast feeding and smoking
      cessation to all clients. Data were analyzed for differences between the IHS
      participants and other Marion County births. RESULTS: Most participants (63%)
      were non-Hispanic blacks aged less than 25 years (56%), without a high school
      diploma or general education development (53%), and enrolled in Medicaid (91%).
      Program participants were more likely to initiate breast feeding than
      nonparticipants (OR, 1.33; 95% CI, 1.10-1.61), and 22% continued to breast feed
      for 6 months. Hispanic women were more likely to breast feed for at least 6
      months (OR, 4.71; 95% CI, 2.32-9.58). Women with advanced education were more
      likely to have quit smoking, as were women who were breast feeding at hospital
      discharge. After controlling for education, IHS clients tended to be less likely
      to continue to smoke during the third trimester (OR, 0.76, 95% CI, 0.49-1.16), as
      were those with a first pregnancy (OR, 0.32; 95% CI, 0.10, 0.98) and no other
      smokers in the home (OR, 0.25; 95% CI, 0.08, 0.74). CONCLUSION: Breast feeding
      and smoking cessation are modifiable risk factors that were impacted by
      behavioral interventions through case management education.

PMID- 22973676
TI  - Special considerations of care and risk management for African American patients
      with type 2 diabetes mellitus.
AB  - It is well documented that African American populations are disproportionately
      affected by type 2 diabetes mellitus compared with their white counterparts. They
      have a higher prevalence of diabetes, a higher rate of diabetes-related
      complications, greater disability from these complications, and poorer control
      and quality of care. In order to improve diabetes care and outcomes in African
      Americans (and indeed all patients with diabetes), a multifactorial approach is
      needed to target all risk factors-not solely hyperglycemia-simultaneously.
      Culturally appropriate initiatives to improve lifestyle behaviors are a first
      step in management. Community-based programs, including those mediated through
      church groups, have reported varying degrees of success in effecting such
      beneficial lifestyle changes. If these measures fail to achieve desirable levels
      of blood glucose, blood pressure, and serum lipids, pharmacologic therapy is
      indicated. However, few evidence-based recommendations regarding the use of some
      drugs in African Americans currently exist due to their underrepresentation in
      randomized controlled clinical trials. Other essential components of diabetes
      care include regular screening for diabetic nephropathy and neuropathy, and eye
      and foot examinations, with prompt referral to specialists when important
      clinical changes are detected.

PMID- 22973677
TI  - Health service deficits and school-aged children with asthma: a population-based
      study using data from the 2007-2008 National Survey of Child Health.
AB  - BACKGROUND: Asthma is one of the most common and costly illnesses of childhood.
      This study addresses health services deficits experienced by school-aged children
      with asthma. METHODS: Analyzing data from the 2007-2008 National Survey of Child
      Health, this cross-sectional study used household income, race/ethnicity, and
      geographic residency as the primary independent variables and health service
      deficits as the dependent variable. RESULTS: Multivariate analysis yielded that
      other/multiracial (odds ratio [OR], 1.234; 95% confidence interval [CI], 1.226
      1.242) and Hispanic (OR, 2.207; 95% CI, 1.226-1.242) school-aged children with
      asthma had greater odds of having health services deficits as did both urban (OR,
      1.106; 95% CI, 1.099-1.113) and rural (OR, 1.133; 95% CI, 1.124-1.142) school
      aged children with asthma. Children with either moderate (OR, 1.195; 95% CI,
      1.184-1.207) or mild (OR, 1.445; 95% CI, 1.431-1.459) asthma had greater odds of
      having a health services deficit than those with severe asthma. Low-income school
      aged children with asthma had greater odds of having a health services deficit
      than high-income children (OR, 1.031; 95% CI, 1.026-1.036). At lesser odds of
      having a health service deficit were those who were African American, of middle
      range income, male, or who were school-aged children with asthma in good to
      excellent health. CONCLUSION: Both African American and other/multiracial school
      aged children were at greater risk of having asthma than either Caucasian or
      Hispanic children. Three vulnerable subgroups of school-aged children with asthma
      rural, Hispanic, and those of low income were the most likely to have health
      service deficits.

PMID- 22973678
TI  - Race and improvements in the use of guideline-recommended therapies for patients
      with heart failure: findings from IMPROVE HF.
AB  - BACKGROUND: Race is associated with differences in use of guideline-recommended
      therapies for patients with heart failure (HF). OBJECTIVE: To evaluate whether a
      practice-based performance improvement intervention is associated with similar
      improvements in evidence-based care for black, white, and race-undocumented
      patients. METHODS: IMPROVE HF is a longitudinal evaluation of a performance
      improvement intervention on use of evidence-based therapies for outpatients with
      HF or prior myocardial infarction and left ventricular ejection fraction less
      than or equal to 35%. Data were available for 7605 patients. Changes in use of
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta
      blocker, aldosterone antagonist, cardiac resynchronization therapy, implantable
      cardioverter-defibrillator therapy, anticoagulant for atrial fibrillation, and HF
      education were analyzed by patient race (black, white, or undocumented/missing).
      Multivariate analyses identified variables independently associated with changes
      in each therapy. RESULTS: There were 686 black patients (9.0%) and 3238 white
      patients (42.6%), and race was undocumented for 3537 (46.5%). Baseline use of B
      blockers and aldosterone antagonists was significantly higher in black patients
      than in the other 2 groups, and use of aldosterone antagonists and HF education
      was higher among black patients at 24 months. Postintervention use of 4 of 7
      therapies increased equitably for the 3 groups, and treatment rates were similar
      between black and white patients for 5 of 7 individual quality measures.
      Improvements in care were independent of race. CONCLUSIONS: These findings offer
      some indication that race-based differences in delivery of evidence-based HF care
      may be decreasing in outpatient cardiology practices. Application of clinical
      decision support and performance feedback may facilitate equitable improvements
      in HF care in outpatient settings regardless of patient race. TRIAL REGISTRATION:
      NCT00303979, wwwv.clinicaltrials.gov.

PMID- 22973679
TI  - Identification and management of sickle cell trait by young physicians.
AB  - BACKGROUND: Sickle cell disease (SCD) is found in many ethnic groups, with the
      highest prevalence of heterozygote ' carriers (sickle cell trait [SCT]) in
      African Americans. SCT is associated with an increased risk of fatal exertional
      heat illness, renal papillary necrosis, and splenic infarction. Since 2006, all
      infants born in the United States are required to be screened for
      hemoglobinopathies as part of newborn screening (NBS). In 2010, as part of a
      legal settlement, the National Collegiate Athletic Association (NCAA) implemented
      SCT screening in division I athletes. METHODS: Members of the American Academy of
      Pediatrics (AAP) Section on Young Physicians were sent up to 4 e-mail survey
      requests to evaluate SCT education during residency, current NBS follow-up
      practice, and awareness of the NCAA policy. Descriptive statistics and chi2
      analyses were performed. RESULTS: Of 871 eligible participants, 355 (41%)
      completed the survey. Respondents were 70% female, 71% white, and 79% general
      pediatricians. Most had experience with SCD during residency and had been taught
      about the medical and reproductive implications of SCT. Virtually all
      pediatricians report SCT to families when identified during NBS, but only 59%
      order confirmatory testing (e.g., hemoglobin electrophoresis) to verify status.
      While 93% counsel about reproductive implications of SCT, only 71% counsel about
      other medical implications. Only 27% were aware of the NCAA policy. DISCUSSION:
      Despite formal SCT education, a significant number of pediatricians do not verify
      NBS results or counsel about the medical implications of SCT. More comprehensive
      AAP guidelines about SCT are needed and must be incorporated into residency
      education.

PMID- 22973681
TI  - On the wisdom of fiddle lessons...

PMID- 22973680
TI  - A woman post scalenectomy and first-rib resection with dilated vertebral venous
      plexus and a facial rash.

PMID- 22973682
TI  - Contagion.

PMID- 22973683
TI  - Question: does enteral feeding adversely impact outcomes in patients with acute
      pancreatitis?

PMID- 22973684
TI  - Brugada pattern mimicking acute coronary syndrome in a febrile state.
AB  - The Brugada type pattern is characterized by a coved or saddleback shaped ST
      segment elevation in the right precordial leads (V1-V3) on a surface 12 lead
      electrocardiogram (ECG). This pattern can be seen spontaneously, induced by
      sodium channel blocking drugs or rarely by hyperthermia. The mechanism is
      secondary to an alteration in the sodium channels induced by a febrile state.
      Such ECG's could easily be mistaken for acute ST segment elevation myocardial
      infarction and thus pose a unique clinical challenge to emergency room
      physicians. We report such a case of fever induced Brugada pattern and discuss
      the underlying mechanisms.

PMID- 22973685
TI  - [Progress in diagnosis and treatment. Editorial: Internal medicine and
      neurological deseases].

PMID- 22973686
TI  - [Progress in diagnosis and treatment. Topics: I. Hypertension, heart diseases and
      neurologic disorders].

PMID- 22973687
TI  - [II. neurological diseases related to diabetes mellitus: 1. Diabetic peripheral
      neuropathies (diabetic polyneuropathy, focal and multifocal diabetic neuropathy,
      painful diabetic neuropathy].

PMID- 22973688
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: II neurological diseases related to diabetes mellitus; 2.
      Cerebral infarction, coma, hypoglycemia].

PMID- 22973689
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: III. Dyslipidemia and neurological disorders (cerebral
      infarction, dementia)].

PMID- 22973690
TI  - [Internal medicine and neurological disease: progress in diagnosis and treatment.
      Topics: IV. Chronic kidney disease (CKD) and cerebrovascular diseases].

PMID- 22973691
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: V. Dementia and life-style related disease].

PMID- 22973692
TI  - [Internal medicine and neurological diseases: progress in diagnosis and treatment
      topics: VI. Neurological diseases in liver, gallbladder, pancreas and
      gastrointestinal disorders].

PMID- 22973693
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: VII. Respiratory disease and cranial nerve disorders].

PMID- 22973694
TI  - [Internal medicine and neurological diseases: progress in diagnosis and treatment
      topics: VIII. Neurological manifestation due to endocrine metabolic disease].

PMID- 22973695
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: IX. Neurological diseases related to hematological diseases:
      1. Coagulopathy and stroke].

PMID- 22973696
TI  - [Internal medicine and neurological diseases: progress in diagnosis and treatment
      topics: IX. Neurological diseases related to hematological disease; 2. M-protein
      and peripheral neuropathies].

PMID- 22973697
TI  - [Internal medicine and neurological diseases: progress in diagnosis and treatment
      topics: X. Neurological disorders in connective tissue disease].

PMID- 22973698
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: XI. Cancer-associated neurological disorders].

PMID- 22973699
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: XII. Neurological disorders in women].

PMID- 22973700
TI  - [Internal medicine and neurological diseases: progress in diagnosis and
      treatment. Topics: XIII. Infection immunity and neurological disorders (Guillain
      Barre syndrome, Fisher syndrome, Crow-Fukase syndrome, influenza-associated
      encephalopathy, AIDS encephalopathy)].

PMID- 22973701
TI  - [Discussion meeting on diagnosis and a key point of the management of
      neurological diseases closely related to various medical condition].

PMID- 22973702
TI  - [Case report; A case of chronic active EB virus infection].

PMID- 22973703
TI  - [Case report; A case of Mycobacterium kyorinense pulmonary infection].

PMID- 22973704
TI  - [Case report; A Japanese case of familial Mediterranean fever with onset in the
      thirties].

PMID- 22973705
TI  - [Case report; Organizing pneumonia secondary to inhalation of dried tsunami
      sludge after Great East Japan Earthquake].

PMID- 22973706
TI  - [The cutting-edge of medicine; (Pro) renin receptor and renal disease].

PMID- 22973707
TI  - [The cutting-edge of medicine; recent topics of NASH].

PMID- 22973708
TI  - [The cutting-edge of medicine; Malignant lymphoma: appropriate treatment
      choices].

PMID- 22973709
TI  - [The cutting-edge of medicine; diagnosis and treatment of malignant
      pheochromocytoma].

PMID- 22973710
TI  - [Series: Knowledge of emergency required for internist; adrenal crisis].

PMID- 22973711
TI  - [Report from the 14th Tokai Chapter Educational Seminar: Strategy for treatment
      of life-related disease].

PMID- 22973712
TI  - [Series: Let's think-clinical quiz (question) (answer); Young female with cough
      and hemoptysis].

PMID- 22973713
TI  - [Series: Clinical study from Japan and its reflections morning hypertension and
      angiotensin receptor blocker/hydrochlorothiazide combination therapy study--MAPPY
      study].

PMID- 22973714
TI  - [Series: For attending physicians: professionalism; healthcare mediation].

PMID- 22973715
TI  - [Series: Diagnosis at a glance].

PMID- 22973716
TI  - [Series: Physicians and disaster medical care; The changes in gastrointestinal
      bleeding and the countermeasures at a major hospital after the Great East Japan
      Earthquake and the tsunami. Report from the hospital located in the disaster
      area].

PMID- 22973717
TI  - [Evaluation of seasonal changes in hemoglobin A1c in diabetic patients].
AB  - In order to evaluate seasonal changes in hemoglobin A1c (HbA1c) values, we
      examined HbA1c values among 34,590 patients in 2010, and calculated the monthly
      average of HbA1c values through the year. HbA1c values were the highest in March
      and the lowest in October with a difference of 0.30%. The similar annual pattern
      was observed in HbA1c values from 2006 to 2009. Then we selected 453 diabetic
      patients whose treatment did not change through the year, and calculated average
      HbA1c values in four seasons each. There were also significant seasonal changes
      in diabetic patients, which were the highest in the spring and the lowest in the
      autumn, especially found in patients with insulin therapy. These effects may be
      caused by cold climate, decreased physical activity, over food intake and body
      weight gain in the winter. These seasonal changes in HbA1c should be concerned in
      the case of health service research, clinical trials and evaluation of the
      effects of medical treatment.

PMID- 22973718
TI  - [Trend survey of ocular infections with bacteria at Toyama University Hospital
      over the past six years--from the standpoint of laboratory examination].
AB  - Specimens of bacterial ocular infections are frequently received in the clinical
      laboratory. However, a comprehensive trend survey of ocular infections with
      bacteria is very rare. Our objective is to understand the current tendency of
      ocular infections with bacteria in patients at Toyama University Hospital from
      the standpoint of laboratory examination. We studied 263 cases of ocular
      infection with bacteria diagnosed at Toyama University Hospital from January 2006
      to December 2011. 123 were male and 140 were female, with a mean age of 61.2(0
      98) years. Specimens were subjected to direct microscopy and culture. Cultures
      were positive in 174(66.2%) patients. The most common bacterial isolate was
      Staphylococcus (28.1%), followed by Corynebacterium (19.3%), Streptococcus
      (9.3%), and Propionibacterium (8.6%). MRSA accounted for 18.8% of all S. aureus
      isolates, and has increased in recent years. The number of bacteria detected was
      larger in March, June, July, August, and October. Age distribution indicated that
      around 70% of bacterial isolates were detected from patients over 60 years old.
      The most common specimen of ocular infections with bacteria was eye discharge
      (detection rate; 87.8%), followed by corneal scraping(41%), aqueous humor (19%),
      and vitreous body (27%). Nearly 80% of bacterial isolates were detected from
      patients with keratitis, endophthalmitis, dacryocystitis, and conjunctivitis. As
      for the disease specific detection rate, endophthalmitis was very low (38.3%).
      The detection rate by years indicated that the way doctors pick up the specimens
      greatly affects the detection rate. Based on this survey, we need close
      cooperation with medical doctors concerning laboratory examination in ocular
      infection with bacteria, and we must improve the detection sensitivity of
      specimens from patients with endophthalmitis.

PMID- 22973719
TI  - A comparative clinical evaluation of the assay of serum extracellular domain of
      HER2 protein using a chemiluminescent immunoassay method in breast cancer
      patients with or without HER2 protein expression in immunohistochemistry.
AB  - OBJECTIVE: The human epidermal growth factor receptor type 2 (HER2) protein has
      been used as a biomarker for breast cancer. A new method based on
      chemiluminescent immunoassay for measuring the serum levels of the extracellular
      domain of HER2 protein (sHER2-ECD) has been developed. Its clinical usefulness
      has not been clearly established. We studied the clinical usefulness of sHER2-ECD
      in monitoring breast cancer patients. METHODS: We examined the clinical
      effectiveness of sHER2-ECD using the ADVIA Centaur XP System in comparison with
      conventional tumor markers (CA15-3 and CEA) in 148 patients with breast cancer
      with or without trastuzumab treatment. RESULTS: The positive rate for sHER2-ECD,
      CA15-3, and CEA in trastuzumab patients (36) was 25.0%, 19.4%, and 16.7%, and
      that in non-trastuzumab patients (112) was 20.5%, 22.3%, and 22.3%, respectively.
      Twenty-three out of 112(20.5%) non-trastuzumab patients were found positive for
      sHER2-ECD in spite of the negative IHC. Measurement of sHER2-ECD and CA15-3
      showed no difference in the expression profile among different clinical stages.
      During long-term observation in patients negative for HER2 protein by
      immunohistochemistry, sHER2-ECD was found to be a relatively sensitive indicator
      of metastasis to distant organs, such as liver and bone, as compared with CA15-3.
      CONCLUSION: sHER2-ECD testing may be a useful tumor marker for monitoring breast
      cancer patients, even in those with negative IHC for the HER2 protein.

PMID- 22973720
TI  - [Clinical evaluation of a novel multiplex HPV genotyping reagent using the
      luminex xMAP technology].
AB  - Of the more than 100 strains of human papillomavirus (HPV) reported to date, 13
      strains are clinically significant due to the highly associated risk of cervical
      cancer. HPV test reagents are currently being developed to aid detection of these
      strains. The present study compared a novel HPV genotyping reagent using a
      Luminex device, which enables simultaneous quantitation of multiple targets using
      fluorescent beads, and gene-specific multiplex polymerase chain reaction (Luminex
      method) with approved in vitro diagnostics. Subjects comprised 256 patients
      examined at our hospital for either secondary cervical cancer testing or follow
      up (mean age, 40 years; age range, 20-85 years) and specimens were obtained using
      a cervical brush and lavage fluid. The HPV-positive rate with the Luminex method
      was 51.4%(132/256), of which single and multiple strain infections constituted
      65.9% (87/132) and 34.1% (45/132), respectively. Correlation testing of 50
      positive and 50 negative Luminex method specimens was conducted using the HPV DNA
      Hybrid Capture II (HCII), revealing high overall (97%[97/100]), positive(100%
      [47/47]) and negative(94.3% [50/53]) concordance rates. Correlation was also high
      for the Clinichip HPV (Clinichip), with overall, positive and negative
      concordance rates of 98% (98/100), 100%(48/48) and 96.2%(50/52), respectively.
      Furthermore, the detection concordance rate with the Clinichip was 95.8% (46/48).
      Sequencing of the seven specimens showing result discrepancies (HCII, n = 3;
      Clinichip, n = 4) confirmed concordance with the Luminex method results in all
      cases, indicating the validity of the present method. The present findings
      suggest that the Luminex method has sufficient response capability for clinical
      application.

PMID- 22973721
TI  - [Development of novel laboratory technology--Chairmen's introductory remarks].
AB  - The theme of the 58th annual meeting is, "Mission and Challenge of Laboratory
      Medicine". This symposium is named, "Development of Novel Laboratory Technology"
      and is held under the joint sponsorship of the Japanese Society of Clinical
      Chemistry and the Japanese Electrophoresis Society. Both societies have superior
      skills at developing methodology and technology. The tools used in the lectures
      are a carbon nanotube sensor, immunochromatography, direct measurement using
      polyanions and detergents, epigenomic analysis and fluorescent two-dimensional
      electrophoresis. All of the lectures will be very helpful and interesting.

PMID- 22973722
TI  - [Development of the HDL-C and LDL-C direct methods and the subsequent evolution].
AB  - Today, more than a decade after the development of direct methods for determining
      HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) concentrations, there are
      calls to review the reagents in response to discrepancies in patient samples with
      increased levels of atypical lipoproteins, such as apoE-rich HDL, IDL, Lp-X, and
      Lp-Y. Seven direct HDL-C assays showed different reactions toward apoE-rich HDL
      in sera from patients with CETP deficiency and cholestasis. On the other hand,
      the reactivity of the direct LDL-C assays to serum samples with elevated levels
      of IDL, Lp-X, and Lp-Y varied considerably between assay kits from each
      manufacturer. We have also examined the anti-atherogenic functions of apoE-rich
      HDL from the serum of healthy individuals and patients with CETP deficiency and
      cholestasis. The ability of apoE-rich HDL to remove cholesterol from cholesterol
      loaded macrophages showed that the apoE-rich HDL from CETP-deficient serum took
      up more cholesterol than apoE-poor HDL (p < 0.01), but no significant differences
      were observed for apoE-rich HDL from patients with cholestasis.

PMID- 22973723
TI  - [Developing technologies for epigenomic analysis and clinical application of
      molecular diagnosis].
AB  - Epigenetic alterations such as DNA methylation play a key role in silencing genes
      in carcinogenesis. DNA methylation leads to the silencing of a variety of genes
      involved in cell-cycle control, apoptosis, cell signaling and DNA repair in
      gastrointestinal cancer. The recent development of methylation analysis offers a
      quantitative, high sensitivity, high throughput and reliable method. This
      approach enabled us to apply methylation analysis in a clinical setting. The miR
      34b/c gene is a tumor suppressor that is frequently silenced by DNA methylation
      in colorectal and gastric cancer (GC). Accurate preoperative diagnosis of
      invasiveness is essential for selecting appropriate therapeutic options for
      colorectal cancer, but the distinction between invasive and non-invasive
      colorectal tumor is often difficult. Methylation levels of miR-34b/c in
      colorectal washing fluid were highly discriminative between invasive and non
      invasive tumors. Previous reports show that H. pylori infection, which plays an
      important role in gastric carcinogenesis, induces the methylation of various
      genes in the noncancerous gastric mucosae. These finding suggest that the
      accumulation of aberrant DNA methylation in noncancerous gastric mucosa is
      involved in the epigenetic field defect. Methylation of miR-34b/c was
      significantly elevated in noncancerous gastric mucosae of multiple GC patients
      compared with those of single GC patients and H. pylori-positive healthy
      individuals. These results suggest that methylation might be a useful marker for
      the diagnosis and risk assessment of cancer.

PMID- 22973724
TI  - [Proteomics for biomarker development toward personalized medicine].
AB  - Cancer is a genetically and clinically diverse disease, and the therapeutic
      strategies should be optimized for individual cases. Recent advances in
      pharmacogenomics have generated molecular targeting anti-cancer drugs, and their
      optimized uses are an emergent challenge. Biomarkers are key tools to assess the
      malignant potential of tumor cells and to establish risk-stratified therapies.
      The proteome is a functional translation of the genome and it directly regulates
      the malignant phenotypes of tumor cells; thus, a proteomic approach could make
      significant contributions to biomarker development. In the past decade,
      proteomics technologies have progressed extensively, and biomarkers to predict
      the response to treatments were developed using clinical materials in various
      types of malignancies. For example, proteomics identified a strong biomarker
      candidate, pfetin, as a novel prognostic biomarker in gastrointestinal stromal
      tumor, where the anticancer drug became available to reduce the risk of post
      operative metastasis. The prognostic utility of pfetin was immunohistochemically
      established by multi-institutional validation studies, and we expect that in the
      near future we will be able to select patients who may need adjuvant therapy by
      measuring the expression of pfetin in surgical specimens. These observations
      suggested the utility of proteomics for biomarker development. Other than the
      application of advanced technologies, the key points in biomarker studies are the
      use of an adequate number of clinical materials with problem-oriented
      experimental designs. Collaborations between basic researchers and clinicians are
      critical for the effective approach towards realistic biomarkers by proteomics.

PMID- 22973725
TI  - [ISO 15189 accreditation and future perspectives-Chairmen's introductory
      remarks].
AB  - Recently, transparency of the organization administration and patient-centered
      medical care such as patient service and satisfaction have been demanded in the
      medical field. The role of the clinical laboratory, one of the organizations in
      the medical field, is to provide quality laboratory data to improve diagnosis and
      treatment. Other than clinical laboratory facilities, education and the ability
      of staff to use it, the management of the organization must be appropriate to
      produce high quality laboratory data. International guidance on how to manage a
      laboratory is shown in ISO 15189. Clinical laboratories with ISO accreditation in
      Europe, Australia and Asia are increasing. On the other hand, only 60
      institutions (10 national university hospitals, 4 public private university
      hospitals, 12 private hospitals and 34 referral laboratories) are accredited in
      Japan. Six speakers spoke at this symposium about the accreditation system of ISO
      15189, the experiences of the acquiring institution and the effect of
      acquisition, as well as the future prospects of ISO 15189. This was a good
      opportunity to become informed about the current situation of ISO 15189 in Japan
      and internationally.

PMID- 22973726
TI  - [Current status of ISO 15189 accreditation system].
AB  - The Japan Accreditation Board (JAB) mainly involves the ISO 15189 accreditation
      system with support from the Japanese Committee for Clinical Laboratory Standards
      (JCCLS). The currently available procedure to obtain accreditation is as below.
      Firstly, it is necessary for applicants to prepare ISO 15189 and related
      documents in each laboratory. Then a JAB assessor will conduct a preliminary
      assessment to check if the applicant is ready to be accredited. Subsequently, a
      team consisting of one to five JAB assessors and/or technical experts will
      conduct the initial assessment, usually for two days. Finally, the team will make
      a recommendation to the JAB Accreditation Committee for Medical Laboratory on its
      evaluation for accreditation. If the Accreditation Committee approves the
      recommendation of the assessment team, the applicant will be granted
      accreditation and issued with a certificate of accreditation. According to EU
      data in February 2011, about 1,300 medical laboratories obtained the ISO 15189
      accreditation. The numbers of accredited laboratories are 482 in Germany, 276 in
      England, 209 in France, 100 in Czechoslovakia etc. Similarly, the data for the
      Asia-Pacific region in June 2011 showed that the numbers of accredited
      laboratories are 638 in Australia, 287 in India, 220 in Canada, 160 in Taiwan
      etc. Although 59 laboratories are accredited in Japan, the ISO 15189
      accreditation is not so widespread compared with other countries. It is now
      expected that the government and/or related bodies will have sufficient
      understanding of this accreditation system to further its development in Japan.
      [Rinsho Byori 60: 653-659, 2012]

PMID- 22973727
TI  - [Quality management of medical laboratory--a survey for National University
      Hospital].
AB  - Since ISO (International Organization for Standardization) 15189 for medical
      laboratories was established in Japan in 2003, 60 medical laboratories had been
      certified until April 2011. Among them, 10 medical laboratories belong to
      national university hospitals. To investigate the current status for the
      development of a quality management system, we carried out a questionnaire survey
      targeting all national university hospitals. ISO and ISO 15189 have already been
      introduced in about 70% of all laboratories and 53% are ready to accept them. In
      medical laboratories that have already accepted ISO 15189, it was suggested that
      their quality management systems have been functioning effectively and a gradual
      decrease of the number of the incidents has been confirmed.

PMID- 22973728
TI  - [Effects of the ISO 15189 accreditation on Nagoya University Hospital].
AB  - The Department of Clinical Laboratory, Nagoya University Hospital acquired ISO
      15189 accreditation in November, 2009. The operation of our Quality Management
      System (QMS) was first surveyed in October, 2010. In this paper, we reported the
      activity for the preparation and operation of our QMS and the effects of ISO
      15189 accreditation. We investigated the changes in the number and content on
      nonconformities, incident reports and complaints before and after accreditation
      as indicators to evaluate the effect of ISO 15189 accreditation. Post
      accreditation, the number of nonconformities and incident reports decreased,
      seeming to show an improvement of quality of the laboratory activity; however,
      the number of complaints increased. We identified the increase of complaints at
      the phlebotomy station. There had been some problems with blood sampling in the
      past, but it seemed that staff had a high level of concern regarding these
      problems at the phlebotomy station and took appropriate measures to resolve the
      complaints. We confirmed that the ISO 15189 accreditation was instrumental in the
      improvements of the safety and efficiency on laboratory works. However there was
      a problem that increase of overtime works to operate the QMS. We deal with
      development of a laboratory management system using IT recourses to solve the
      problem.

PMID- 22973729
TI  - [Acquisition of accreditation ISO 15189 and view of the future--case of a private
      college].
AB  - We received ISO 15189 accreditation (International Organization for
      Standardization 15189) in 2009. Several effects from the subjective points are
      shown below, 1. The reliability of the test results has improved. 2. Skill or
      knowledge level of staff has improved. 3. Internal recognition has improved. 4.
      Procedures to prevent accidents have been enforced. 5. Management system has
      improved. 6. Effective management tool for the manager. In addition to high costs
      for qualification and maintenance, extensive human resources are required to
      prepare documents. We need to make further efforts to aim at better cost
      effectiveness.

PMID- 22973730
TI  - [From the position of a private sector hospital: ISO 15189 acquisition by a
      clinical laboratory, and quality management system deployment in the whole
      hospital].
AB  - St. Mary's Hospital Medical Inspecting Center acquired ISO 15189 authorization in
      December, 2007. In the process of authorization acquisition, measures were taken
      to improve various quality issues, and a marked effect was seen in patient
      services and medical safety control. Furthermore, we tried to improve ward
      nursing management using ISO, drew up standard operating procedures through
      detailed job analysis, and enabled ward operation standardization. In this paper,
      while describing the effect of ISO 15189 on clinical examinations, we refer to
      the significance of improving quality of hospital management which our clinical
      laboratory lead to.

PMID- 22973731
TI  - [Trends toward EBLM in the EBM era].
AB  - Evidence-based laboratory medicine (EBLM) is the strategic application of
      evidence-based medicine (EBM) to laboratory medicine. Although trends toward EBLM
      were inspired by the movements of EBM and EBLM shares a common policy with EBM,
      EBLM has many of its own characteristics to be considered from the aspects of not
      only science but also clinical practice.

PMID- 22973732
TI  - [Unbiased estimation of factorial effect by using analysis of covariance or
      propensity score method for observational studies in laboratory medicine].
AB  - This paper deals with bias-reduction techniques for observational studies in
      evidence-based laboratory medicine (EBLM). In the field of laboratory medicine,
      many observational studies have been performed since it is difficult to design
      randomized experimental studies. The results of these observational studies have
      usually been affected by various types of biases in observational data that could
      not be controlled by the researchers. In randomized experiments, random
      assignment provides unbiased estimations of the treatment effect. In contrast, in
      observational studies, incorrect (biased) estimations arise from the imbalance
      between the covariates for the treatment/exposure group and the control group;
      therefore, information regarding confounding factors that affect both an outcome
      variable and assignment should be used to construct a multivariate model for
      minimizing bias. Covariate adjustment helps to reduce bias by correcting the
      imbalance in covariates. Analysis of covariance (ANCOVA) is an important method
      for covariate adjustment. The ANCOVA model is an extension of multiple regression
      models that can statistically control the effects of covariates. The propensity
      score method has recently been used as a covariate adjustment method in applied
      research. Because propensity scores concentrate the information on covariates,
      conditional expectations can be easily computed. In this paper, both methods were
      exemplified in a study on sex-based differences in HDL cholesterol levels.
      Similar unbiased estimates of sex-based differences were obtained using both
      methods, as opposed to an incorrect estimate obtained using univariate analysis.
      The results emphasize that covariate adjustment should be used to obtain credible
      evidence in observational studies.

PMID- 22973733
TI  - [Improving data warehouse environments for efficient analysis of long time-series
      data].
AB  - Medical records contain enormous amounts of data. It is important to extract
      useful evidence from such data and feedback to clinical medicine. Evidence-based
      medicine (EBM) was introduced in the 1990s and has been widely used for more than
      20 years, however, hospital information system environments that take advantage
      of the ideas of EBM have not yet been established. Recently, the numbers of
      medical institutions with multilateral search systems for the medical records
      stored in data warehouses (DWHs) have been increasing, but these institutions'
      systems cannot deal fully with issues such as data reliability and high
      dimensional, high-speed searches. DWHs can control long time-series data.
      Although, the measurement methods and analytical equipment used have been
      modified and improved with advances in testing techniques, this may have induced
      shifting and/or fragmentation of these types of data. Furthermore, database
      design has to be flexible to satisfy the various demands of information
      retrieval; systems must therefore have the structures to deal with such demands.
      We report here our new system infrastructure, which exchanges data in order to
      absorb the data shifting associated with changes in the testing methods. The
      system enables the preparation of DWH environments that can be used to seamlessly
      analyze long time-series data, record in knowledge databases the results of
      comprehensive analyses of institutions' characteristics of laboratory diagnoses,
      and use the data in education, research and clinical practice.

PMID- 22973734
TI  - [Recent progress in the diagnosis of meibomnian gland dysfunction].

PMID- 22973735
TI  - [Morphological changes in meibomian glands following radiotherapy].
AB  - PURPOSE: To examine the morphological changes in meibomian glands using
      noncontact infrared meibography in patients undergoing radiotherapy and to
      compare the results with those of a normal population. CASES AND METHOD: Thirteen
      eyes of 8 patients (2 men and 6 women; 65.1 +/- 17.6 years, mean +/- standard
      deviation) diagnosed as having ocular adnexal lymphoma and had undergone
      radiotherapy were included in this study. Meibomian gland morphological changes
      (meiboscore) were assessed by noncontact meibography. The results were compared
      with those of forty-one eyes of 21 healthy volunteers (9 men and 12 women ; 66.9
      +/- 11.6 years). RESULTS: The meiboscore was 3.69 +/- 0.75 in the irradiation
      group and 2.41 +/- 1.34 in the control group, showing a significant difference
      between the groups (p = 0.0029). When compared with the irradiated and fellow
      eyes in the patients with unilateral radiotherapy, the mean meiboscore of
      irradiated eyes (4.00 +/- 1.00) was higher than that of the fellow eyes (2.66 +/-
      0.57) even though there was no significant difference. CONCLUSION: Radiotherapy
      causes morphological changes in the meibomian glands such as atrophy and dropout.

PMID- 22973737
TI  - [Fundus photoplanimetry of the optic nerve head in the Sakurae Study].
AB  - PURPOSE: To explore the fundus photoplanimetric distribution of the optic nerve
      head in a population-based health survey conducted in Sakurae area, in Shimane,
      Japan(the Sakurae Study). METHODS: After the exclusion of poor quality images
      from the 1660 right eye-fundus photos obtained from the Sakurae Study in 1991,
      1583 photos were digitized, and then were planimetrically analyzed using a newly
      developed computer software, CDSketch. The parameters calculated included
      vertical and horizontal cup-to-disc (C/D) ratios, superior and inferior rim-to
      disc (R/D) ratios, disc and cup vertical-to-horizontal (V/H) ratios, and disc
      macular distance-to-disc diameter (DM/DD) ratio. RESULTS: For the vertical and
      horizontal C/D, superior and inferior R/D, disc and cup V/H, and DM/DD ratios,
      mean values were calculated to be 0.58, 0.59, 0.20, 0.18, 1.11, 1.09, 2.60,
      respectively, and median values were calculated to be 0.58, 0.59, 0.19, 0.18,
      1.11, 1.09, 2.57, respectively; no parameter showed any remarkably skewed
      distribution. The vertical C/D ratio was positively correlated with the cup V/H
      ratio, but was not correlated with the disc V/ H ratio. The vertical and
      horizontal C/D, and the disc and cup V/H ratios were negatively correlated with
      the DM/DD ratio. CONCLUSIONS: The distributions of the various optic nerve head
      parameters and their correlations in the Sakurae Study are reported. Both mean
      and median values of the vertical C/D ratio were approximately 0.6 in this study
      population. These values were larger than the previously reported C/D ratios
      obtained by direct ophthalmoscopic observations and/or by subjective methods.

PMID- 22973736
TI  - [Retrospective study of ocular complications in patients with human
      immunodeficiency virus infection before and after HAART].
AB  - PURPOSE: To describe ocular complications in patients with human immunodeficiency
      virus (HIV) infection before and after highly active antiretroviral
      therapy(HAART). MATERIALS AND METHOD: We retrospectively reviewed the medical
      records of 261 patients who underwent HAART and visited our clinic between April,
      2007 and March, 2010, and recorded ocular complications, CD4 cell counts, visual
      acuity and other relevant patient information. RESULTS: Befor HAART patients were
      found to have the following conditions: HIV retinopathy (41 cases),
      cytomegalovirus (CMV) retinitis (23 cases), and others (6 cases); and after HAART
      HIV retinopathy (5 cases), CMV retinitis (16 cases), Immune recovery uveitis(IRU)
      (4 cases), and others(9 cases). The average CD4+ T-cell counts at diagnosis of
      CMV retinitis were 45.2/microl before and 116.7/microl after HAART. CONCLUSIONS:
      Since a substantial number of patients develop CMV retinitis after the initiation
      of HAART, we need to examine patients to check for either the onset or
      reactivation of CMV retinitis and IRU even after HAART.

PMID- 22973738
TI  - [Long-term surgical results of initial trabeculotomy combined with sinusotomy
      performed inferiorly].
AB  - PURPOSE: To evaluate retrospectively the long-term effects of initial
      trabeculotomy combined with sinusotomy performed inferiorly. PATIENTS AND METHOD:
      Enrolled were 128 eyes of 100 patients who received initial glaucoma surgery. In
      36 eyes, the removal of Schlemm's canal endothelium was also performed (removed
      group). The results were compared with the intact group RESULTS: In the primary
      open angle glaucoma (POAG), mean intraocular pressure (IOP) at 3 years after
      surgery was 14.6 (intact) and 15.4 mmHg (removed). Kaplan-Meier life-table
      analysis showed that qualified success rates for the intact group at 8 years were
      62.2% and for the removed group at 5 years 45.2% defined by 20 mmHg or lower. The
      results in developmental glaucoma (DG) were similar to those in POAG. No
      statistical differences in postoperative IOP between the intact and removed
      groups were seen in either POAG or DG. In exfoliation glaucoma (XFG), mean IOPs
      for the intact group at 3 years were 17.3 mmHg and for the removed group at 2
      years 15.4 mmHg. The success rates for the intact group at 3.5 years were 25.2%
      and for the removed group at 4.5 years 64.3%. The results in the intact group
      were worse than in the POAG patients. Although visual disturbance was seen in 13%
      of the patients, the major cause was the progression of the cataracts.
      CONCLUSIONS: The long-term results were the same as those of previous reports on
      surgery performed superiorly, including the frequency of visual disturbance.
      However the removal of Schlemm's canal endothelium is necessary in XFG for better
      IOP control.

PMID- 22973739
TI  - [Effects of selective laser trabeculoplasty treatment in steroid-induced
      glaucoma].
AB  - PURPOSE: To evaluate the effectiveness of selective laser trabeculoplasty (SLT)
      on steroid-induced glaucoma. METHODS: The study included 46 eyes of 41 subjects
      who were followed up for at least 12 months after SLT. The included 10 eyes with
      steroid-induced glaucoma, 16 eyes with primary open angle glaucoma (POAG), 10
      eyes with pseudoexfoliation glaucoma (PEX.G) and 10 eyes with mixed glaucoma
      (Mixed. G). The range of the SLT laser was 360 degrees. Intraocular pressure
      (IOP) before and after SLT, and cumulative survival rate after SLT were
      determined. RESULTS: Significant decreases in IOP were observed after SLT in the
      steroid-induced glaucoma group, the POAG group and the PEX.G group. At 12 months
      after SLT, preoperation IOP decreased by 35.9% (29.9 +/- 7.5 mmHg to 17.9 +/- 2.2
      mmHg) in the steroid-induced glaucoma group, 13.2% (20.0 +/- 3.0 mmHg to 17.3 +/-
      3.1 mmHg) in the POAG group, 10.7% (21.1 +/- 4.0 mmHg to 18.1 +/- 4.1 mmHg) in
      the PEX.G group and 6.9% (21.3 +/- 1.9 mmHg to 19.9 +/- 3.4 mmHg) in the Mixed.G
      group. Cumulative survival rates were 80%, 56.3%, 50.0%, 40.0% in the steroid
      induced glaucoma, POAG, PEX.G, and Mixed. G groups, respectively, at 12 months
      after SLT (Logrank test, p = 0.467). CONCLUSION: These data suggest that SLT
      increased IOP reduction rates for steroid-induced glaucoma more than for any
      other group.

PMID- 22973740
TI  - Looking forward.

PMID- 22973741
TI  - Participating in the Medicare eRx Incentive Program.

PMID- 22973742
TI  - From the chair of the RAS-ACS: Leadership skills continue to serve past RAS-ACS
      chairs in their current roles.

PMID- 22973743
TI  - Surgical leadership and political advocacy.

PMID- 22973744
TI  - Advanced degrees for surgeons and their impact on leadership.

PMID- 22973745
TI  - Women leaders in surgery: past, present, and future.

PMID- 22973746
TI  - Surgical leadership across generations.

PMID- 22973747
TI  - Surgery at the end of life: for love or money?

PMID- 22973748
TI  - From battlefield to bedside--and back again.

PMID- 22973749
TI  - Training global surgery fellows.

PMID- 22973750
TI  - SafeCare offers quality framework in resource-restricted settings.

PMID- 22973751
TI  - What's new in renal cell carcinoma.

PMID- 22973752
TI  - ["It takes two to tango"].

PMID- 22973753
TI  - [From passive recipient to active partner].

PMID- 22973754
TI  - [From the viewpoint of the patient and professional woman].

PMID- 22973755
TI  - [Not the catheter, but the child is at the center].

PMID- 22973756
TI  - [The country needs new management concepts].

PMID- 22973757
TI  - [Forward into a new era].

PMID- 22973758
TI  - [It must not always be a garden].

PMID- 22973759
TI  - [We grant dying patients time" (interview by Urs Luthi)].

PMID- 22973760
TI  - [The pills of discord].

PMID- 22973761
TI  - [A world where the future doesn't exist].

PMID- 22973762
TI  - [Quality, security and job satisfaction under the magnifying glass].

PMID- 22973763
TI  - [A division of labor in patient care].

PMID- 22973764
TI  - [Active prevention is required].

PMID- 22973765
TI  - [And so one cares for our second brain?].

PMID- 22973766
TI  - [Slow medicine].

PMID- 22973767
TI  - [ROL's 30th anniversary. We dedicate it to you, Nestor].

PMID- 22973768
TI  - [Cooperating and strengthening our society].

PMID- 22973769
TI  - [A glance at the 35 years of evolution of nursing in Spain].

PMID- 22973770
TI  - [The evaluation of continuous training in healthcare organisations. A
      bibliographic review].
AB  - OBJECTIVE: To analyze and consider scientific documents which develop the impact
      of Continuous Training in health sciences. DESIGN: Literature review STUDY
      SELECTION: 18 articles are included, organised in two categories: a) the theory
      and application of Continuous Training to healthcare professionals, b) the impact
      of Continued Training in healthcare organisations. RESULTS: All of the authors
      position themselves clearly in favour of CT in healthcare organisations in all
      professional categories (whether healthcare or not), as a strategic instrument of
      change and growth. The importance of assessing the impact that both professionals
      and institutions have on the end-product (i.e. the health of people) is
      emphasised. Despite the difficulties involved, to establish their impact is of
      vital importance in order to verify their benefits and effectiveness.
      CONCLUSIONS: Regular assessment is essential for introducing changes in training
      programmes so that they are adapted to the requirements of healthcare
      organisations and the needs of their professionals.

PMID- 22973771
TI  - [35 years of health excellence].

PMID- 22973772
TI  - [35th anniversary of the publication Revista ROL de Enfermeria].

PMID- 22973773
TI  - [On the 35th anniversary of Revista ROL de Enfermeria].

PMID- 22973774
TI  - [ROL, my accomplice journal].

PMID- 22973775
TI  - Reflections on acute severe asthma.

PMID- 22973776
TI  - Plagiarism: the bete noire of scientific communication.

PMID- 22973777
TI  - Experience with treatment of pulmonary alveolar proteinosis from a tertiary care
      centre in north India.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a disorder characterised by
      accumulation of lipids and proteins in the alveoli, with the resultant symptoms
      ranging from indolent subclinical disease to progressive respiratory failure.
      METHODS: We retrospectively studied five patients with PAP managed at our center
      between January 2007 and April 2010, with whole lung lavage (WLL) and/or
      subcutaneous granulocyte macrophage-colony stimulating factor (GM-CSF) therapy.
      Patients undergoing WLL under general anaesthesia were supplemented with three
      months of GM-CSF therapy. Pre- and post-lavage symptom assessment was performed
      with a 10-point, symptom-based visual analogue scale. RESULTS: Their mean age was
      37.6-7.0 years; there were four males. Diagnosis of PAP [idiopathic (n=3);
      secondary to Nocardia (n=1)] was established by surgical lung biopsy in four
      patients who presented with respiratory failure. Three patients with idiopathic
      PAP (n=3) were treated with a combination of GM-CSF and WLL; one patient with
      secondary PAP was treated with antibiotics alone. In another patient
      transbronchial lung biopsy was used to diagnose PAP and GM-CSF alone was
      administered. All patients were followed up for a median period of two years
      (range 0.5-3 years). Significant improvement was achieved in all the patients
      with therapeutic WLL and/or GM-CSF. CONCLUSIONS: Whole lung lavage appeared to be
      an effective and safe therapy in patients with PAP. Efficacy of simultaneous
      administration of GM-CSF and WLL in the treatment of PAP merits further study.

PMID- 22973778
TI  - Sarcoidosis in north Indian population: a retrospective study.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown origin
      most commonly involving the lungs. Sarcoidosis is frequently misdiagnosed due to
      its clinico-radiological resemblance to tuberculosis (TB). Hence, the present
      study was undertaken with the aim of studying the clinico-radiological profile of
      sarcoidosis in the Indian context. METHODS: We retrospectively studied 146
      patients diagnosed to have sarcoidosis during the period 2001-2010 at one of the
      respiratory units at Vallabhbhai Patel Chest Institute. RESULTS: Majority of them
      (70%) were more than 40 years of age; females comprised 58.2% of the patients.
      Before coming to our clinic, 30% patients had been misdiagnosed to have TB. Cough
      (89.7%) was the most common presenting symptom; joint symptoms (28.8%) and end
      inspiratory crepitations at lung bases (49.3%) were other salient manifestations.
      Cutaneous involvement and digital clubbing were rarely seen. Pulmonary function
      testing showed restriction with impaired diffusion in 72.7% patients. The most
      common radiological feature was bilaterally symmetrical hilar lymphadenopathy.
      Transbronchial lung biopsy (TBLB) had a very high diagnostic yield (90.8%).
      CONCLUSIONS: Sarcoidosis is often misdiagnosed as TB in India. Transbronchial
      lung biopsy has high diagnostic yield in sarcoidosis.

PMID- 22973779
TI  - Congenital malformation of lung parenchyma: 15 years experience in a thoracic
      surgical unit.
AB  - OBJECTIVE: To review the surgical management of congenital malformations of lung
      parenchyma in a thoracic surgery unit over a period of 15 years. METHODS: We
      carried out a retrospective analysis of records of all patients who had surgery
      for congenital malformations of lung parenchyma between 1995 and 2010. RESULTS:
      Forty-five patients underwent surgery for congenital lung lesions out of 3735
      thoracotomies performed during the study period. The lesions included 29 lung
      sequestrations, 12 bronchogenic cysts, 3 congenital lobar emphysema and one
      congenital cystic adenomatoid malformation. Only 26 (26%) cases were diagnosed
      preoperatively. Twenty-eight (62.2%) patients underwent lobectomy, 5 (11.1%)
      patients had pneumonectomy, and 10 (22.2%) patients had removal of cyst while 2
      (0.45%) patients had lung resection with repair of the oesophageal connection. No
      mortality was recorded. One patient had post-operative complication of
      oesophageal fistula which was successfully managed conservatively. The follow-up
      was between 8 months to 14 years. All patients were asymptomatic and had no
      physical limitations during the follow-up. CONCLUSIONS: Surgery is curative and
      produces good long-term result in patients with congenital malformations of lung
      parenchyma. It should be offered to patients as a therapeutic option where
      indicated and feasible.

PMID- 22973780
TI  - Comparison of frequency of undiagnosed chronic obstructive pulmonary disease in
      current or former tobacco smokers having ischaemic heart disease.
AB  - BACKGROUND AND OBJECTIVES: This study compares the frequency of undiagnosed
      chronic obstructive pulmonary disease (COPD) in tobacco smokers suffering from
      ischaemic heart disease (IHD) and analyses the association of COPD severity with
      status, type and duration of smoking. METHODS: An analytical cross-sectional
      study conducted in current and former cigarette, hookah and combined cigarette
      and hookah smokers with IHD to detect previously undiagnosed COPD through
      spirometry. RESULTS: Among 124 males with IHD, majority [74 (59.7%)] were former
      smokers and were in the age ranged between 42 to 78 years. All had dyspnoea up to
      grade 4 and 64 (51.6%) also reported chronic cough and sputum production.
      According to type of smoking, 64 (51.6%) smoked cigarettes, 30 (24.2%) smoked
      hookah and 30 (24.2%) smoked both hookah and cigarettes. Forty-seven (37.9%) were
      found to have COPD, 24 (37.5%) among cigarette smokers, 12 (40%) among hookah
      smokers, while 11 (36.7%) were from cigarette and hookah smokers. Duration of
      smoking, its type and magnitude had no association with severity of COPD.
      CONCLUSIONS: The frequency of undiagnosed COPD is high in smokers with IHD.
      Hookah and combined hookah and cigarette smokers are almost as susceptible to
      develop COPD as are cigarette smokers.

PMID- 22973781
TI  - A large bulla simulating diaphragmatic eventration. Chronic obstructive pulmonary
      disease (COPD) with a large left lower lobe bulla.

PMID- 22973782
TI  - Pulmonary cavitation and hydropneumothorax associated with pulmonary embolism.

PMID- 22973783
TI  - Tracheal polyp treated with endobronchial electrocautery.
AB  - Fibroepithelial polyps of trachea are extremely rare. Here, we report a case of
      tracheal polyp in a 40-year-old woman that was managed successfully with
      endobronchial electrocautery with a review of the relevant literature.

PMID- 22973784
TI  - Leuconostoc garlicum: an unusual pathogen in the era of vancomycin therapy.
AB  - Leuconostoc garlicum, belonging to the family of Leuconostocaceae, is a catalase
      negative, Gram-positive ovoid cocci, intrinsically resistant to vancomycin.
      Clinical infection by Leuconostoc garlicum is rare. We report a case of
      respiratory tract infection subsequent to vancomycin therapy.

PMID- 22973785
TI  - Rare association of eventration of left hemidiaphragm with ipsilateral thyroid
      agenesis.
AB  - Eventration is a well-known congenital malformation of the diaphragm, usually
      asymptomatic and diagnosed incidentally on chest radiography. It is sometimes
      associated with a number of other congenital syndromes and anomalies. We report a
      rare case of eventration of left hemidiaphragm associated with gastric volvulus,
      ipsilateral thyroid agenesis and microphthalmia.

PMID- 22973786
TI  - Tubercular nodular episcleritis.
AB  - A 12-year-old male child suffering from pain, redness, blurring and watering of
      right eye since six months was diagnosed as suffering from nodular episcleritis
      probably tuberculosis. Diagnosis was supported by the additional finding of
      enlarged cervical lymph node found on aspiration cytology. Complete resolution
      occurred after anti-tuberculosis therapy.

PMID- 22973787
TI  - What now? Reform law provides opportunities for leaders to better serve our
      communities.

PMID- 22973788
TI  - Pulling it all together: what makes health IT more meaningful?

PMID- 22973789
TI  - Innovative strategies for hospital-physician EHR integration.

PMID- 22973790
TI  - The ethics of mission and margin.

PMID- 22973791
TI  - Leadership: how do leaders eliminate fear?

PMID- 22973792
TI  - Teamwork: remedying dysfunctional teams.

PMID- 22973793
TI  - Communication: eliminate credibility blind spots.

PMID- 22973794
TI  - The myth of comprehensive policies.

PMID- 22973795
TI  - A progressive step toward healthcare equality.

PMID- 22973796
TI  - Collaborating to help frequent ED patients.

PMID- 22973797
TI  - The Supreme Court decision: implications and opportunities.

PMID- 22973798
TI  - Coaching for organizational success.

PMID- 22973799
TI  - Transforming care delivery to focus on patient outcomes.

PMID- 22973800
TI  - Improving health through health IT.

PMID- 22973801
TI  - The economics of physician integration.

PMID- 22973802
TI  - New procedure to record the rupture of bonds between macromolecules and the
      surface of the quartz crystal microbalance (QCM).
AB  - It is shown that an increase in the amplitude of QCM shear oscillations during
      frequency scanning around the resonance frequency is accompanied (at a definite
      voltage) by distortions in the amplitude-frequency dependence for QCM. We
      demonstrated that these distortions are connected to the rupture of
      macromolecules from the QCM surface. It is shown that the identification of the
      rupture of particles and macromolecules from the QCM surface can be carried out
      by relying on the analysis of these distortions of the amplitude-frequency
      dependence. The distortions were distinguished as a signal. The number of broken
      bonds can be estimated from the value of this distortion signal, and the
      threshold voltage applied to the system can be used to estimate the rupture force
      to high accuracy. Using the proposed method, we estimated the strength of a
      physical bond, which was 3 pN. This procedure can be useful for studying
      biological objects and represents an advanced step in the development of the REVS
      (rupture event scanning) technique.

PMID- 22973803
TI  - Association between headache and serum 25-hydroxyvitamin D: the Tromso Study:
      Tromso 6.
AB  - BACKGROUND: High prevalence of headache has been associated with high latitude,
      thus suggesting a relation with vitamin D. However, there are so far no reports
      on the association between serum 25-hydroxyvitamin D (25[OH]D) and headache.
      OBJECTIVE: To investigate the association between headache and serum 25(OH)D in a
      general population. METHODS: Cross-sectional study based on questionnaires from
      11,614 persons who participated in the sixth survey of the Tromso Study (Tromso
      6) carried out in 2007-2008. The data were stratified according to smoking status
      and analyzed with regard to migraine and non-migraine headache. Adjustments were
      done for age, body mass index (BMI), gender, season, chronic diseases, education,
      physical exercise, and alcohol consumption. RESULTS: Headache of non-migraine
      type was associated with low levels of serum 25(OH)D with an odds ratio (OR) of
      1.20 (1.04-1.39) in the lowest quartile as compared to the highest serum 25(OH)D
      quartile. No significant association was found between migraine and serum
      25(OH)D. CONCLUSION: Non-migraine headache was associated with low levels of
      serum 25(OH)D. Although adjustment were done for possible confounders, this
      finding may still reflect lifestyle rather than causality, and further studies
      are needed to investigate this. No association was found between serum 25(OH)D
      and migraine.

PMID- 22973804
TI  - Rapid heating of Alaska pollock and chicken breast myofibrillar protein gels as
      affecting water-holding properties.
AB  - The gelation response of salted muscle minces to rapid versus slow heating rates
      is thought to differ between homeotherm and poikilotherm species. This study
      investigated water-holding (WH) properties of pastes prepared from refined
      myofibrils, at equal pH, of chicken breast versus Alaska pollock both during
      [cook loss (CL)] and following [expressible water (EW)] their cooking by rapid
      [microwave (MW)] versus slow [water bath (WB)] heating and whether such
      properties were related to gel matrix structure parameters and water mobility.
      Results did not confirm the industrial experience that pastes of meat from
      homeotherms benefit from slower cooking. Gels of equally high WH ability (low CL
      or EW) were made by rapid heating when the holding time did not exceed 5 min
      prior to cooling, which was sufficient for completion of gelation. Reduced CL and
      EW correlated with larger and smaller amplitudes of T21 and T22 water pools,
      respectively, measured by time-domain nuclear magnetic resonance (TD-NMR). 

PMID- 22973805
TI  - Monogalactosyldiacylglycerols, potent nitric oxide inhibitors from the marine
      microalga Tetraselmis chui.
AB  - Methanolic extracts of some marine and freshwater microalgae were tested for
      their nitric oxide (NO) inhibitory activity on lipopolysaccharide-induced NO
      production in RAW264.7 macrophage cells. Among the tested extracts, Tetraselmis
      chui extract showed the strongest NO inhibitory activity, thus selected for
      further study. NO inhibitory activity guided isolation led to identification of
      two monogalactosyldiacylglycerols (MGDGs) (2S)-1-O-(6Z,9Z,12Z,15Z
      octadecatetranoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetranoyl)-3-O-beta-D
      galactopyranosylglycerol (1) and (2S)-1-O-(9Z,12Z,15Z-octadecatrinoyl)-2-O
      (4Z,7Z,10Z,13Z-hexadecatetranoyl)-3-O-beta-D-galactopyranosylglycerol (2) from
      the MeOH extract of T. chui. The stereo-chemistry of 1 was elucidated by
      classical degradation method. MGDGs 1 and 2 showed strong NO inhibitory activity
      compared to N(G)-methyl-L-arginine acetate salt, a well known NO inhibitor used
      as a positive control. Isolated MGDGs suppressed NO production through down
      regulation of inducible NO synthase protein. A structure activity relationship
      study suggested that the polyunsaturated fatty acids of the MGDGs are responsible
      for NO inhibition. Moreover, increasing unsaturation on the fatty acid side
      chains enhanced the NO inhibitory potency of the MGDGs.

PMID- 22973806
TI  - Maternal correlates of maternal child feeding practices: a systematic review.
AB  - Establishing healthy eating habits early in life is one important strategy to
      combat childhood obesity. Given that early maternal child feeding practices have
      been linked to child food intake and weight, identifying the maternal correlates
      of maternal child feeding practices is important in order to understand the
      determinants of childhood obesity; this was the overall aim of the current
      review. Academic databases were searched for studies examining the relationship
      between maternal child feeding practices and parenting, personal characteristics
      and psychopathology of mothers with preschoolers. Papers were limited to those
      published in English, between January 2000 and June 2012. Only studies with
      mothers of normally developing children between the ages of 2 and 6 years were
      included. There were no restrictions regarding the inclusion of maternal
      nationality or socioeconomic status (SES). Seventeen eligible studies were
      sourced. Information on the aim, sample, measures and findings of these was
      summarised into tables. The findings of this review support a relationship
      between maternal controlling parenting, general and eating psychopathology, and
      SES and maternal child feeding practices. The main methodological issues of the
      studies reviewed included inconsistency in measures of maternal variables across
      studies and cross-sectional designs. We conclude that the maternal correlates
      associated with maternal child feeding practices are complex, and the pathways by
      which maternal correlates impact these feeding practices require further
      investigation.

PMID- 22973807
TI  - Lateral organisation in nineteenth-century studio photographs is influenced by
      the direction of writing: a comparison of Iranian and Spanish photographs.
AB  - The direction of reading has been found to have a significant effect upon
      aesthetic preference, with left-to-right readers showing a preference for stimuli
      with a rightward directionality while right-to-left readers prefer stimuli with a
      leftward directionality. This study looks at a large set of posed, studio
      photographs to study the cultural interaction between direction of reading and
      lateral organisation, comparing a corpus of 735 nineteenth-century photographs
      from Iran (right-to-left reading) with a similar corpus of 898 photographs from
      Spain (left-to-right readers). Five separate types of composition were studied:
      linear ordering, usually by height; couples; individuals posing by a chair;
      individuals posing by a table; and portraits. Lateral preferences were found for
      all five types of photograph, with the lateral organisation of Iranian
      photographs being the reverse of that in the Spanish photographs. These data
      provide support for the influence of direction of reading upon aesthetic
      organisation in naturalistically produced photographs.

PMID- 22973808
TI  - Atypical lateralisation in emotional prosody in men with schizotypy.
AB  - Individuals high in schizotypy have been shown to reveal reduced lateralisation
      in verbal processing which may be influenced by an impaired left hemisphere
      performance. However, little is known about schizotypy and right hemisphere
      functions such as emotional perception. The present study focuses on atypical
      lateralisation in language and emotional prosody in Impulsive Non-conformity
      (IMP), a specific aspect of schizotypy. A total of 41 participants (20 females)
      performed a dichotic listening linguistic and emotional prosody task, which
      typically shows a right ear advantage (REA) and left ear advantage (LEA),
      respectively. A median split based on the IMP scale included in the Oxford
      Liverpool Inventory of Feelings and Experiences was used to divide the sample
      into high and low scorers. The results revealed a selective reduction of the LEA
      in the prosody task in high-IMP males. Females high and low in IMP revealed
      typical lateralisation in both tasks. The results indicate that high-IMP males
      are especially prone to atypical lateralisation in emotional prosody, which
      parallels those findings in male patients with schizophrenia. The results suggest
      similarities in sex-specific atypical brain organisation between schizotypy and
      schizophrenia.

PMID- 22973809
TI  - Hemispheric processing of inferences during text comprehension: the role of
      consistency and task difficulty.
AB  - Although the hemispheres likely carry out different processes during reading,
      currently little is known about how the consistency effect and the difficulty of
      the task influences hemispheric processing during text comprehension. In the
      current study participants read texts promoting an inference, and performed a
      lexical decision task to inference-related targets presented to the left visual
      field-right hemisphere or the right visual field-left hemisphere. To manipulate
      the consistency of information targets were either consistent or inconsistent
      with the inference. To manipulate difficulty the antecedent and its referent were
      either separated by two sentences (i.e., the less-difficult condition) or four
      sentences (i.e., the more-difficult condition). In the consistent condition
      facilitation was greater in the left hemisphere than the right hemisphere. In the
      inconsistent condition facilitation was greater in the right hemisphere than the
      left hemisphere. When analyses were combined across conditions, consistent
      targets showed greater facilitation in the left hemisphere than in the right
      hemisphere. Interestingly the level of difficulty did not mediate how the
      hemispheres process inferences. The current findings suggest that the consistency
      of information, rather than the difficulty of a task, primarily influences
      inference generation in the cerebral hemispheres.

PMID- 22973810
TI  - Pair bonding and lateral neck-resting preferences in captive Caribbean flamingos
      (Phoenicopterus ruber).
AB  - When flamingos rest, they typically lay their head on their back and curve their
      neck to either the right or left of their body, with both individual and
      population-level lateral preferences for rightward neck resting when preferences
      are tracked over time (Anderson, Williams, & O'Brien, 2009). The present study
      attempted to replicate these previous neck-resting preferences, to examine how
      they changed over time, and to examine the possibility of a relationship between
      lateral neck-resting preference and pair bonding in captive Caribbean flamingos
      (Phoenicopterus ruber) housed at the Philadelphia Zoo (Philadelphia, PA, USA).
      Results successfully replicated the individual- and population-level lateral
      preferences for rightward neck resting, and demonstrated that these preferences
      were stable over time. Moreover, individual flamingos that demonstrated stronger
      pair bond strengths tended to differ less from their partners in terms of neck
      resting preference than did those birds displaying weaker pair bond strengths,
      suggesting a relationship between laterality and social cohesion.

PMID- 22973811
TI  - Lateralisation in wine olfactory threshold detection: comparison between experts
      and novices.
AB  - The study of olfactory lateralisation in humans has given rise to many
      publications, but few studies have been focused on possible differences in
      relation to the experience towards specific odorants. The aim of the present
      study was to compare unilateral detection thresholds for three wines between
      expert and novice judges. Additionally, irritation and hedonic valence were also
      evaluated using monorhinal stimulations. Results showed that the novices had
      lower detection thresholds with the left nostril--whatever the wine--compared to
      the experts. Concerning hedonic rating, no nostril difference existed in the
      expert group contrary to the novice group, which evaluated wines as more pleasant
      with the left than with the right nostril. Irritation rating appeared not to be
      lateralised in both groups. However, the novices rated the three wines as more
      irritant than the experts with the right as well as with the left nostril. These
      findings suggest that the level of experience induced specific differences in
      terms of lateralisation between wine experts and novices.

PMID- 22973812
TI  - Season of birth and handedness in young adults.
AB  - This study explored the relationship between season of birth and handedness,
      taking into account gender and nationality variables. Young adults from three
      countries (2120 females and 1353 males; 877 Spanish, 2184 Italian, and 412
      French), aged from 18 to 30 years, filled the Edinburgh Handedness Inventory
      (EHI). According to the literature, the percentage of left-handed participants in
      the whole sample was 9.30%. The distribution of left- and right-handed
      participants was not significantly different among the seasons of birth. The
      present data do not support a significant season of birth effect on handedness in
      young adults.

PMID- 22973813
TI  - Metaphors and verbal creativity: the role of the right hemisphere.
AB  - Ample research suggests that the right cerebral hemisphere plays a central role
      in verbal creativity as well as in novel metaphor comprehension. The aim of the
      present study was to directly examine the relation between verbal creativity and
      right hemisphere involvement during novel metaphor comprehension. Thus 30 healthy
      adults were asked to fill in the Hebrew version of the Remote Association Test to
      assess their level of creativity. In addition, reaction times and error rates
      were measured while these participants performed a semantic judgement task on two
      word expressions presented in a divided visual field paradigm. The word pairs
      comprised four types of semantic relations: novel metaphors, conventional
      metaphors, literal word pairs, and meaningless word pairs. Correlations were
      conducted to assess the relation between level of creativity and processing of
      the four pair types in the two cerebral hemispheres. The main finding was of a
      significant negative correlation between degree of creativity and reaction times
      to novel metaphor processing in the right hemisphere, thus supporting the
      involvement of this cerebral hemisphere in both tasks. Results are discussed in
      light of linguistic theories and recent neuroscientific evidence regarding
      relative hemispheric involvement during semantic processing.

PMID- 22973814
TI  - The cerebral hemispheres differ in their capacity for content-to-level binding
      but not for identification: evidence from conjunction errors obtained with
      bilateral hierarchical stimuli.
AB  - It is widely assumed that the right and left cerebral hemispheres are specialised
      for processing the global and local information of hierarchical stimuli,
      respectively. This idea has further been specified in the content-to-level
      binding theory (Hubner & Volberg, 2005) by stating that the hemispheres differ in
      their efficiency for binding the contents of a stimulus to their respective
      level. In contrast, it is assumed that the hemispheres do not differ in their
      capacity for the identification of the information at the two levels. This latter
      hypothesis was tested in the present experiment by presenting a hierarchical
      letter to each visual field. As expected, there were visual field effects only
      for errors involving the erroneous binding between a letter and a level. For
      errors that result from the mislocalisation of a letter, there were no visual
      field effects. Together, the data support the hypothesis that the hemispheres do
      not differ in their identification capacity.

PMID- 22973815
TI  - Are left-handers really more anxious?
AB  - Research examining anxiety and handedness is inconclusive. Davidson and Schaffer
      (1983) found left-handers had higher trait anxiety, while Beaton and Moseley
      (1991) found no state or trait differences. Such studies potentially have
      methodological issues, and we have argued that handedness related reactivity
      differences (Wright & Hardie, 2011) suggest that state anxiety needs to be
      measured within a context. Thus the current study investigated state and trait
      anxiety levels in an experimental situation. We found left-handers had
      significantly higher state scores, supporting the right hemisphere's role in
      negative affect and inhibition. It also fits with predictions based on the
      behavioural inhibition system's role in the revised reinforcement sensitivity
      theory (rRST). No trait differences were found, but there was a significant
      relationship between trait and state anxiety. Using ANCOVA to control for the
      influence of trait anxiety on state anxiety, we still found a handedness effect.
      When participant's trait anxiety levels were similar, left-handers showed a
      relatively larger state response. We conclude that in the context of an
      experiment, state anxiety was directly correlated with trait anxiety but that the
      relatively higher reactivity of left-handers may be a major influence on how they
      respond in a new situation.

PMID- 22973817
TI  - Reduced risk of poststroke pneumonia in thrombolyzed stroke patients with
      continued statin treatment.
AB  - BACKGROUND: Pneumonia is a frequent complication after stroke with strong impact
      on clinical outcome. Statins have pleiotropic immunmodulatory properties and were
      recently shown to exert beneficial effects on the development and clinical course
      of pneumonia. AIMS: We aimed to investigate whether statin use is associated with
      a reduced risk of poststroke pneumonia in acute ischemic stroke patients treated
      with tissue plasminogen activator within 4.5hours. METHODS: Data was extracted
      from a local register including all consecutive stroke patients who received
      thrombolysis at our institution. Prior statin use was identified retrospectively
      from clinical records and had to be continued after hospital admission.
      Poststroke pneumonia was diagnosed according to standardized criteria of US
      Centers for Disease Control and Prevention. Mortality and functional outcome at
      three-months were further assessed. RESULTS: Overall, 481 ischemic stroke
      patients were analyzed. Continued statin use was documented in 17% of the
      patients. Frequency of pneumonia was 11%. Patients with statin use were less
      likely to develop poststroke pneumonia (5% vs. 13%, P = 0.04). After
      multivariable adjustment for known risk factors for poststroke pneumonia (age,
      stroke severity, dysphagia, male sex and diabetes), statin treatment was
      negatively associated with pneumonia (OR 0.31; 95% CI 0.10-0.94). Occurrence of
      pneumonia independently predicted three-month mortality and functional outcome.
      CONCLUSIONS: Use of statins in acute ischemic stroke patients who receive
      thrombolysis might reduce the risk of poststroke pneumonia. Further studies are
      warranted to validate this finding.

PMID- 22973818
TI  - Ulceration of mature surgical scars following nonablative fractional
      photothermolysis associated with intralesional lidocaine injections.

PMID- 22973819
TI  - Motivations for, and perceptions and experiences of participating in, a cluster
      randomised controlled trial of a HIV-behavioural intervention in rural South
      Africa.
AB  - Empirical research on ethical issues in HIV-prevention and gender-based violence
      research, critical for honing ethical and safety guidelines, is limited. In this
      paper we describe South African young people's motivations for participating in
      randomised controlled trial, the prevalence of negative occurrences,
      participation regrets and associated factors. This trial partly followed, but
      also deviated from, the WHO safety guidelines for research on violence against
      women. A total of 1085 women and 985 men provided information two years after the
      trial start. Most participated for HIV testing and to help their community. Fewer
      reported motivation by the financial incentive. Minor adverse events included
      upset from questions on childhood experiences and arguments at home with
      siblings. Just under 1 in 10 (8.1% women, 9.8% men) regretted participation.
      Factors were associated with this were keeping some questions secret from their
      partners, feeling sad about questions on childhood, quarrelling at home and, for
      women, being motivated by the incentive. Men who had been physically violent to a
      partner were twice as likely to regret participation. There were no recorded
      adverse effects from the deviations from the ethical guidelines. Participation
      regrets mostly stemmed from problems in participants' families preceding the
      research. There was no evidence that the research had been unsafe.

PMID- 22973820
TI  - Supracostal tubeless percutaneous nephrolithotomy: a retrospective cohort study.
AB  - PURPOSE: To evaluate the safety of tubeless percutaneous nephrolithotomy in
      patients undergoing supracostal percutaneous renal access. PATIENTS AND METHODS:
      Between October 1999 and October 2010, 302 patients underwent percutaneous
      nephrolithotomy via a supracostal access tract. Two hundred forty-eight (82.1%)
      patients had a nephrostomy tube placed at the end of the case and 54 (17.9%) did
      not. The medical records of both cohorts were compared regarding patient
      demographics (age, sex, body mass index, preoperative creatinine level),
      operative characteristics (estimated blood loss, length of stay, treatment
      efficacy), and complication rates (overall, thoracic, hemorrhage necessitating
      transfusion). RESULTS: Patient demographics did not differ between the tubeless
      and nephrostomy tube groups. Estimated blood loss was significantly less in the
      tubeless patients (67 mL vs 123 mL; P=0.019). The tubeless group had a shorter
      mean length of stay than the nephrostomy tube group (2.5 vs 3.4 days, P<0.01).
      Treatment success was comparable between the two groups (tubeless 81.5% vs
      nephrostomy tube 77.8%; P=0.553). Overall complication (P=0.765) and blood
      transfusion (P=0.064) rates were equivalent. Chest complications were higher in
      the tubeless group (22.2%) compared with the nephrostomy tube patients (10.9%)
      (P=0.024). Nevertheless, chest complications necessitating intervention were not
      different (P=0.152). CONCLUSIONS: Tubeless supracostal percutaneous
      nephrolithotomy was associated with less intraoperative blood loss and a shorter
      hospital stay. Although the tubeless group experienced more chest complications
      overall, the need for intervention was no different among the two cohorts.
      Tubeless supracostal percutaneous nephrolithotomy appears safe.

PMID- 22973822
TI  - Systematic review: managing suboptimal treatment responses in autoimmune
      hepatitis with conventional and nonstandard drugs.
AB  - BACKGROUND: Corticosteroid treatment for autoimmune hepatitis has been shown by
      randomised controlled clinical trials to ameliorate symptoms, normalise liver
      tests, improve histological findings and extend survival. Nevertheless,
      suboptimal responses to corticosteroid treatment still occur. AIM: To describe
      the current definitions, frequencies, clinical relevance and treatment options
      for suboptimal responses, and to discuss alternative medications that have been
      used off-label for these occurrences. METHODS: Literature search was made for
      full-text papers published in English using the keyword 'autoimmune hepatitis'.
      Authors' personal experience and investigational studies also helped to identify
      important contributions to the literature. RESULTS: Suboptimal responses to
      standard therapy include treatment failure (7%), incomplete response (14%), drug
      toxicity (13%) and relapse after drug withdrawal (50-86%). The probability of a
      suboptimal response prior to treatment is higher in young patients and in
      patients with a severe presentation, jaundice, high MELD score at diagnosis,
      multilobular necrosis or cirrhosis, antibodies to soluble liver antigen, or
      inability to improve by clinical indices within two weeks or by MELD score within
      7 days of conventional corticosteroid treatment. Management strategies have been
      developed for the adverse responses and nonstandard drugs, including
      mycophenolate mofetil, budesonide, ciclosporin, tacrolimus, sirolimus and
      rituximab, are emerging as rescue therapies or alternative frontline agents.
      CONCLUSIONS: Once diagnosed, the suboptimal response should be treated by a
      highly individualised and well-monitored regimen, preferentially using first-line
      therapy. Nonstandard drugs warrant consideration as salvage or second-line
      therapies.

PMID- 22973821
TI  - Diversity in recognition of glycans by F-type lectins and galectins: molecular,
      structural, and biophysical aspects.
AB  - Although lectins are "hard-wired" in the germline, the presence of tandemly
      arrayed carbohydrate recognition domains (CRDs), of chimeric structures
      displaying distinct CRDs, of polymorphic genes resulting in multiple isoforms,
      and in some cases, of a considerable recognition plasticity of their carbohydrate
      binding sites, significantly expand the lectin ligand-recognition spectrum and
      lectin functional diversification. Analysis of structural/functional aspects of
      galectins and F-lectins-the most recently identified lectin family characterized
      by a unique CRD sequence motif (a distinctive structural fold) and nominal
      specificity for l-Fuc-has led to a greater understanding of self/nonself
      recognition by proteins with tandemly arrayed CRDs. For lectins with a single
      CRD, however, recognition of self and nonself glycans can only be rationalized in
      terms of protein oligomerization and ligand clustering and presentation. Spatial
      and temporal changes in lectin expression, secretion, and local concentrations in
      extracellular microenvironments, as well as structural diversity and spatial
      display of their carbohydrate ligands on the host or microbial cell surface, are
      suggestive of a dynamic interplay of their recognition and effector functions in
      development and immunity.

PMID- 22973823
TI  - Collective synthesis of Lycopodium alkaloids and tautomer locking strategy for
      the total synthesis of (-)-lycojapodine A.
AB  - The collective total synthesis of Lycopodium alkaloids (+)-fawcettimine (1), (+)
      fawcettidine (2), (+)-alopecuridine (4), (-)-lycojapodine A (6), and (-)-8
      deoxyserratinine (7) has been accomplished from a common precursor (15) based on
      a highly concise route inspired by the proposed biosynthesis of the fawcettimine-
      and serratinine-type alkaloids. An intramolecular C-alkylation enabled efficient
      installation of the challenging spiro quaternary carbon center and the aza
      cyclononane ring. The preparation of the tricyclic skeleton as well as the
      establishment of the correct relative stereochemistry of the oxa-quaternary
      center were achieved by hydroxyl-directed SmI(2)-mediated pinacol couplings. An
      unprecedented tandem transannular N-alkylation and removal of a Boc group was
      discovered to realize a biosynthesis-inspired process to furnish the desired
      tetracyclic skeleton. Of particular note is the unique and crucial tautomer
      locking strategy employed to complete the enantioselective total synthesis of (-)
      lycojapodine A (6). The central step in this synthesis is the late-stage
      hypervalent iodine oxidant (IBX or Dess-Martin periodinane)/TFA-mediated tandem
      process, which constructed the previously unknown carbinolamine lactone motif and
      enabled a biomimetic transformation to generate (-)-lycojapodine A (6) in a
      single operation.

PMID- 22973824
TI  - Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in
      mouse models of acute lung injury.
AB  - INTRODUCTION: Acute lung injury (ALI) is a common disease in critically ill
      patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an
      enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from
      arachidonic acid. It has been shown that 12/15-LO is involved in the regulation
      of vascular permeability during ALI. METHODS: To test whether 12/15-LO
      participates in leukocyte recruitment into the lung, we investigated the role of
      12/15-LO in mouse models of lipopolysaccharide (LPS)-induced pulmonary
      inflammation and acid-induced ALI, a clinically relevant model of acute lung
      injury. RESULTS: The increase in neutrophil recruitment following LPS inhalation
      was reduced in 12/15-LO-deficient (Alox15(-/-)) mice and in wild-type (WT) mice
      after the blocking of 12/15-LO with a pharmacological inhibitor. Bone marrow
      chimeras revealed that 12/15-LO in hematopoietic cells regulates neutrophil
      accumulation in the interstitial and alveolar compartments, whereas the
      accumulation of neutrophils in the intravascular compartment is regulated by
      12/15-LO in non-hematopoietic and hematopoietic cells. Mechanistically, the
      increased plasma levels of the chemokine CXCL1 in Alox15(-/-) mice led to a
      reduced response of the neutrophil chemokine receptor CXCR2 to stimulation with
      CXCL1, which in turn abrogated neutrophil recruitment. Alox15(-/-) mice also
      showed decreased edema formation, reduced neutrophil recruitment and improved gas
      exchange in an acid-induced ALI model. CONCLUSIONS: Our findings suggest that
      12/15-LO modulates neutrophil recruitment into the lung by regulating
      chemokine/chemokine receptor homeostasis.

PMID- 22973825
TI  - Age-related changes in prostate zonal volumes as measured by high-resolution
      magnetic resonance imaging (MRI): a cross-sectional study in over 500 patients.
AB  - Study Type--Diagnosis (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Benign prostatic hyperplasia is the most
      common symptomatic disorder of the prostate and its severity varies greatly in
      the population. Various methods have been used to estimate prostate volumes in
      the past including the digital rectal examination and ultrasound measurements.
      High-resolution T2 weighted MRI can provide accurate measurements of zonal
      volumes and total volumes, which can be used to better understand the etiology of
      lower urinary tract symptoms of men. OBJECTIVE: * To use ability of magnetic
      resonance imaging (MRI) to investigate age-related changes in zonal prostate
      volumes. PATIENTS AND METHODS: * This Institutional Review Board approved, Health
      Insurance Portability and Accountability Act-compliant study consisted of 503
      patients who underwent 3 T prostate MRI before any treatment for prostate cancer.
      * Whole prostate (WP) and central gland (CG) volumes were manually contoured on
      T2-weighted MRI using a semi-automated segmentation tool. WP, CG, peripheral zone
      (PZ) volumes were measured for each patient. * WP, CG, PZ volumes were correlated
      with age, serum prostate-specific antigen (PSA) level, International Prostate
      Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) scores. RESULTS: *
      Linear regression analysis showed positive correlations between WP, CG volumes
      and patient age (P < 0.001); there was no correlation between age and PZ volume
      (P= 0.173). * There was a positive correlation between WP, CG volumes and serum
      PSA level (P < 0.001), as well as between PZ volume and serum PSA level (P=
      0.002). * At logistic regression analysis, IPSS positively correlated with WP, CG
      volumes (P < 0.001). * SHIM positively correlated with WP (P= 0.015) and CG (P=
      0.023) volumes. * As expected, the IPSS of patients with prostate volumes (WP,
      CG) in first decile for age were significantly lower than those in tenth decile.
      CONCLUSIONS: * Prostate MRI is able to document age-related changes in prostate
      zonal volumes. * Changes in WP and CG volumes correlated inversely with changes
      in lower urinary tract symptoms. * These findings suggest a role for MRI in
      measuring accurate prostate zonal volumes; have interesting implications for
      study of age-related changes in the prostate.

PMID- 22973826
TI  - Higher age at onset of type 1 diabetes increases risk of macular oedema.
AB  - PURPOSE: To investigate whether age at onset of type 1 diabetes is a risk factor
      for clinically significant macular oedema (CSME). METHODS: A sample of 1354
      patients with a mean duration of diabetes 24.6 +/- 11.6 years was drawn from the
      FinnDiane Study population and divided into age at onset groups 0-4 (n = 184), 5
      14 (n = 662) and 15-40 years (n = 508). Type 1 diabetes was defined as age at
      onset <=40 years, C-peptide negativity and insulin treatment initiated within 1
      year of diagnosis. Retinopathy status was assessed from fundus photographs and
      stereoscopic fundus examinations and graded with the ETDRS scale. RESULTS: After
      30 years of diabetes, the estimated cumulative incidences of CSME were 17% (95%
      CI 11-26) in age at onset group 0-4 years, 27% (95% CI 23-32) in age at onset
      group 5-14 years and 34% (95% CI 27-41) in age at onset group 15-40 years (p =
      0.002, Gray's test). In a competing risks regression model, adjusted for
      covariates selected with Bayesian information criteria, age at onset 5-14 years
      (HR 1.89 [95% CI 1.22-2.91], p = 0.004), and age at onset 15-40 years (HR 3.72
      [95% CI 2.35-5.89], p < 0.0001), were significant overall risk factors for CSME
      (p < 0.0001). Higher ETDRS score (HR 1.04 ([95% CI 1.03-1.05], p < 0.0001), HbA1c
      (HR 1.12 [95% CI 1.02-1.23], p = 0.016), and total cholesterol (HR 1.19 [95% CI
      1.04-1.37], p = 0.013) also increased the risk of CSME. CONCLUSIONS: Higher age
      at onset of type 1 diabetes is a significant risk factor for macular oedema. This
      suggests that ageing may modify the risk of retinopathy in type 1 diabetes.

PMID- 22973827
TI  - Non-physician cataract surgeons in Sub-Saharan Africa: situation analysis.
AB  - OBJECTIVES: Non-physician cataract surgeons (NPCS) provide cataract surgical
      services in some Sub-Saharan African (SSA) countries. However, their training,
      placement, legal framework and supervision have not been documented. We sought to
      do so to inform decision-making regarding future training. METHODS: Standard
      questionnaires were sent to national eye coordinators and other ophthalmologic
      leaders in Africa to collect information. Face-to-face interviews were conducted
      at training programmes in Ethiopia, Tanzania and Kenya, and email interviews were
      conducted with directors at training programmes in the Gambia and Malawi.
      RESULTS: Responses were provided for 31/39 (79%) countries to which
      questionnaires were sent. These countries represent about 90% of the population
      of SSA. Overall, 17 countries have one or more NPCS; two-thirds of the total 245
      NPCS are found in only three countries. Thirty-six percent of NPCS work alone,
      but a formal functioning supervision system was reported to be present in only
      one country. The training centres are similar and face similar challenges.
      CONCLUSIONS: There is considerable variation across SSA in the use and acceptance
      of NPCS. The placement and support of NPCS after training generally does not
      follow expectations, and training centres have little role in this. Overall,
      there was no consensus on whether the cadre, as it is currently viewed, is
      necessary, desirable or will contribute to addressing cataract surgical needs in
      SSA.

PMID- 22973828
TI  - The impact of preoperative anxiety and education level on long-term mortality
      after cardiac surgery.
AB  - BACKGROUND: Psychosocial factors have shown independent predictive value in the
      development of cardiovascular diseases. Although there is strong evidence to
      support the role of psychosocial factors in cardiovascular mortality, there is a
      scarcity of knowledge about how these factors are related. Therefore, we
      investigated the relationship between depression, anxiety, education, social
      isolation and mortality 7.5 years after cardiac surgery. METHODS: After informed
      consent, 180 patients undergoing cardiac surgery between July 2000 and May 2001
      were prospectively enrolled and followed for ten years. During the follow-up
      period, the patients were contacted annually by mail. Anxiety (Spielberger State
      Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory,
      BDI) and the number and reason for rehospitalizations were assessed each year.
      Those patients who did not respond were contacted by telephone, and national
      registries were searched for deaths. RESULTS: During a median follow-up of 7.6
      years (25th to 75th percentile, 7.4 to 8.1 years), the mortality rate was 23.6%
      (95% confidence interval [CI] 17.3-29.9; 42 deaths). In a Cox regression model,
      the risk factors associated with an increased risk of mortality were a higher
      EUROSCORE (points; Adjusted Hazard Ratio (AHR):1.30, 95%CI:1.07-1.58)), a higher
      preoperative STAI-T score (points; AHR:1.06, 95%CI 1.02-1.09), lower education
      level (school years; AHR:0.86, 95%CI:0.74-0.98), and the occurrence of major
      adverse cardiac and cerebral events during follow up (AHR:7.24, 95%CI:2.65-19.7).
      In the postdischarge model, the same risk factors remained. CONCLUSIONS: Our
      results suggest that the assessment of psychosocial factors, particularly anxiety
      and education may help identify patients at an increased risk for long-term
      mortality after cardiac surgery.

PMID- 22973829
TI  - A Delphi study to construct a CanMEDS competence based inventory applicable for
      workplace assessment.
AB  - BACKGROUND: During workplace based learning students develop professional
      competences and an appropriate performance. To gain insight in the learning
      process and to evaluate competences and performance, assessment tools are
      essential and need to be of good quality. We aimed to construct a competence
      inventory applicable as an instrument to measure the content validity of
      workplace based assessment tools, such as portfolio. METHODS: A Delphi study was
      carried out based on the CanMEDS Roles Framework. In three rounds, experts (N =
      25-30) were invited to score the key competences per CanMEDS role on relevance (6
      point Likert-scale), and to comment on the content and formulation bearing in
      mind its use in workplace based assessment. A descriptive analysis of relevances
      and comments was performed. RESULTS: Although all competences were scored as
      relevant, many comments pointed at a lack of concrete, transparent and applicable
      descriptions of the key competences for the purpose of assessment. Therefore, the
      CanMEDS roles were reformulated in this Delphi procedure as concrete learning
      outcomes, observable and suitable for workplace based assessment. CONCLUSIONS: A
      competence based inventory, ready for validating workplace based assessment
      tools, was constructed using a Delphi procedure and based on a clarification and
      concretisation of the CanMEDS roles.

PMID- 22973830
TI  - Cytokine expression profiles of immune imbalance in post-mononucleosis chronic
      fatigue.
AB  - BACKGROUND: As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein
      Bar virus (EBV) and other systemic infections; our objective was to describe
      differences in immune activation in post-infective CFS (PI-CFS) patients and
      recovered controls. We studied 301 adolescents prospectively over 24 months
      following the diagnosis of monospot-positive infectious mononucleosis (IM). We
      found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively.
      METHODS: Using chemiluminescent imaging we measured the concentrations of IL-1a,
      1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-gamma, TNF-alpha and TNF
      beta in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and
      12 recovered controls at 24 months post-infection. RESULTS: Standard comparative
      analysis indicated significant differences in IL-8 and 23 across subject groups.
      In constructing a linear classification model IL-6, 8 and 23 were selected by two
      different statistical approaches as discriminating features, with IL-1a, IL-2 and
      IFN-gamma also selected in one model or the other. This supported an assignment
      accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus
      recovered controls. CONCLUSION: These results suggest that co-expression patterns
      in as few as 5 cytokines associated with Th17 function may hold promise as a tool
      for the diagnosis of post-infectious CFS.

PMID- 22973831
TI  - Complicated malaria and other severe febrile illness in a pediatric ward in
      Libreville, Gabon.
AB  - BACKGROUND: Although a substantial decline of Plasmodium falciparum infection is
      observed in Africa following implementation of new control strategies, malaria is
      still considered as the major cause of febrile illness in hospitalized African
      children. The present study was designed to assess the management of febrile
      illness and to determine the proportion of children with febrile illness
      hospitalized for primary diagnosis of malaria who had confirmed complicated
      malaria after implementation of new malaria control strategies in Libreville,
      Gabon. METHODS: Demographic, clinical and biological data from hospitalized
      children with fever or a history of fever, with a primary diagnosis of clinical
      malaria, aged less than 18 years old, who benefited from hematological
      measurements and microscopic malaria diagnosis, were recorded and analyzed during
      a prospective and observational study conducted in 2008 in the Centre Hospitalier
      de Libreville. RESULTS: A total of 418 febrile children were admitted at hospital
      as malaria cases. Majority of them (79.4%) were aged below five years. After
      medical examination, 168 were diagnosed and treated as clinical malaria and,
      among them, only 56.7% (n = 95) had Plasmodium falciparum positive blood smears.
      Age above five years, pallor, Blantyre Coma Score <=2 and thrombocytopenia were
      predictive of malaria infection. Respiratory tract infections were the first
      leading cause of hospitalization (41.1%), followed by malaria (22.7%); co
      morbidities were frequent (22%). Less than 5% of suspected bacterial infections
      were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria.
      Almost half (46%) of the children who received antimalarial therapy had negative
      blood smears. Likewise, antibiotics were frequently prescribed without
      bacteriological confirmation. CONCLUSIONS: The use of clinical symptoms for the
      management of children febrile illness is frequent in Gabon. Information,
      training of health workers and strengthening of diagnosis tools are necessary to
      improve febrile children care.

PMID- 22973832
TI  - Editorial Comment from Dr Kitta to effect of intrathecal administration of E
      series prostaglandin 1 receptor antagonist in a cyclophosphamide-induced cystitis
      rat model.

PMID- 22973836
TI  - Editorial. Layered double hydroxide-based materials.

PMID- 22973833
TI  - Social phenotypes in genetic syndromes.

PMID- 22973837
TI  - Letter to the editor: Hypersensitivity to lamivudine and emtricitabine.

PMID- 22973838
TI  - Studies on the essential intramolecular interaction between the A1 and A2 domains
      of von Willebrand factor.
AB  - Haemostasis depends on the balanced participation of von Willebrand factor (vWF),
      a large multimeric and multidomain glycoprotein with essential role during the
      initial steps of blood clotting. Mature vWF circulates in plasma with the form of
      multimers comprised of several domains with diverse functions. More specifically,
      the A1 domain of vWF plays crucial role in haemostasis, regulating the mechanism
      of platelet adhesion in sites of vascular injury while A2 domain regulates the
      normal turnover of vWF. Recent studies have implied that an intramolecular
      interaction between A1 and A2 domains exists, which prevents platelets adhesion
      and subsequently inhibits the initial step of the blood coagulation mechanism. In
      an effort to elucidate the essential nature of the interaction between these two
      domains, we produced and purified the corresponding recombinant unmodified
      polypeptides. The secondary structure of the two domains was studied individually
      and as a mixture using circular dichroism spectroscopy. The observed interaction
      was verified by ELISA competition assays using antibodies and their ability to
      form productive interactions was further characterized kinetically. In silico
      analysis (docking and molecular dynamics simulations) of the A1-A2 binding
      indicated three possible structural models highlighting the crucial, for this
      interaction, region.

PMID- 22973839
TI  - Quantitative analysis and pharmacokinetics study of integrin antagonist AP25 in
      rat plasma.
AB  - BALB/c mice were immunized by highly immunogenic recombinant proteins containing
      amino acid sequence of integrin antagonist AP25. Antibody against AP25 was
      prepared and purified by affinity chromatography. An indirect enzyme-linked
      immunosorbent assay for qualitative analysis of AP25 in rat plasma samples was
      successfully established. The assay was successfully applied to determine the
      pharmacokinetic parameters of AP25 in SD rats by intravenous administration of
      AP25 and then the rat plasma protein binding of AP25 were determined in vitro. In
      order to investigate the specificity of ELISA for detection of prototype AP25 in
      plasma, the proportion of AP25 prototype drug in the ELISA signal value was
      validated by HPLC. These results can serve as valuable future clinical trials.

PMID- 22973840
TI  - Structural analysis as an alternative to identify and determine mode of action of
      antimicrobial peptides: proposition of a kinetic model based on molecular
      dynamics studies.
AB  - Antimicrobial peptides (AMPs) constitute an important alternative in the search
      for new treatments against pathogens. We analyzed the sequence variability in
      cytokine and chemokine proteins to investigate whether these molecules contain a
      sequence useful in the development of new AMPs. Cluster analysis allowed the
      identification of tracts, grouped in five categories showing structure and
      sequence homology. The structure and function relationship among these groups,
      was analyzed using physicochemical parameters such as length, sequence, charge,
      hydrophobicity and helicity, which allowed the selection of a candidate that
      could constitute an AMP. This peptide comprises the C-terminal alpha-helix of
      chemokines CXCL4/PF-457-70. Far-UV CD spectroscopy showed that this molecule
      adopts a random conformation in aqueous solution and the addition of 2, 2, 2
      trifluoroethanol (TFE) is required to induce a helical secondary structure. The
      CXCL4/PF-457-70 peptide was found to have antimicrobial activity and very limited
      hemolytic activity. The mechanism of action was analyzed using model kinetics and
      molecular dynamics. The kinetic model led to a reasonable assumption about a rate
      constant and regulatory step on its mechanism of action. Using molecular dynamics
      simulations, the structural properties the CXCL4/PF-457-70 have been examined in
      a membrane environment. Our results show that this peptide has a strong
      preference for binding to the lipid head groups, consequently, increasing the
      surface density and decreasing the lateral mobility of the lipids alters its
      functionality.

PMID- 22973841
TI  - Surface acidic amino acid of Pseudomonas/Halomonas chimeric nucleoside
      diphosphate kinase leads effective recovery from heat-denaturation.
AB  - One of the hallmarks of halophilic properties is reversibility of thermal
      unfolding. A nucleoside diphosphate kinase (NDK) from a moderate halophile
      Halomonas sp. 593 (HaNDK) follows this behavior. His-tagged chimeric NDK
      (HisPaHaNDK) consisting of an N-terminal half of a non-halophilic Pseuodomonas
      aeruginosa NDK (PaNDK) and a Cterminal half of HaNDK loses this reversible
      property, indicating a critical role of the N-terminal portion of PaNDK in
      determining the reversibility of the chimeric protein. Various mutations were
      introduced at Arg45 and Lys61, based on the model NDK structure. It appears that
      having Glu at position 45 is critical in conferring the thermal reversibility to
      HisPa- HaNDK chimeric protein.

PMID- 22973842
TI  - Purification and biophysical characterization of an 11S globulin from Wrightia
      tinctoria exhibiting hemagglutinating activity.
AB  - Wrightia tinctoria globulin (WTG), one of the major seed storage proteins, was
      isolated for the first time from seeds of the medicinal plant. WTG was extracted
      and purified to homogeneity in two steps using anion-exchange and size-exclusion
      chromatographies. On an SDS-PAGE gel under non-reducing conditions, a major band
      of ~56 kDa was observed; under reducing conditions, however, two major
      polypeptides, one with molecular weight ~32-34 kDa and the other with molecular
      weight ~22-26 kDa were observed. Intact mass determination by MALDI-TOF supported
      this observation. The N-terminal amino acid sequence of WTG matched in NCBI
      database with an expressed sequence tag obtained from the c-DNA of developing
      embryo m-RNA of Wrightia tinctoria. The EST sequence was further substantiated by
      partial de novo internal sequencing using MALDI-TOF/TOF. The high sequence
      homology with seed storage protein 11S globulin confirmed that WTG is a type of
      11S globulin. Circular dichroism analysis showed that the secondary structure of
      WTG consists predominantly of beta-sheets (44.2%) and moderate content of alpha
      helices (10.3%). WTG showed hemagglutinating property indicating that the protein
      may possess lectin-like activity. WTG was crystallized at 20 A degrees C by the
      vapour diffusion method using PEG 400 as precipitant. The crystals belonged to
      the orthorhombic space group P212121 with cell dimensions of a=109.9A, b=113.2A
      and c=202.2A with six molecules per asymmetric unit. Diffraction data were
      collected to a resolution of 2.2A under cryocondition. Preliminary structure
      solution of WTG indicated the possibility of a hexameric assembly in its
      asymmetric unit.

PMID- 22973843
TI  - Crystal structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc substrate
      complex.
AB  - MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas
      aeruginosa performing one of the key membrane steps of peptidoglycan synthesis
      catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor
      substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the
      crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP
      GlcNAc and compared it with the previously solved complex from E. coli. The
      structure reveals a large-scale conformational change in the relative
      orientations of the N- and C-terminal domains, which has the effect of widening
      the cofactor binding site and displacing the UDP-GlcNAc donor. These results
      suggest new opportunities to design potent inhibitors of peptidoglycan
      biosynthesis. 

PMID- 22973844
TI  - o-Alkylselenenylated benzoic acid accesses several sites in serum albumin
      according to fluorescence studies, Raman spectroscopy and theoretical
      simulations.
AB  - In the circulatory system, serum albumin (SA) is an important transporter of the
      majority of molecules with biological activity. We focused the current study on
      the anti-inflammatory compound, o-alkylselenenylated benzoic acid (ALKSEBEA), to
      determine its ability to access SA. Herein, we employed experimental procedures
      (fluorescence studies, Raman spectroscopy) and docking study on SA obtained from
      the Protein Data Bank and key conformers obtained from molecular dynamics
      simulations. The results show that ALKSEBEA accesses SA using a cooperative
      behavior according to fluorescence studies. In addition, the Raman results
      indicate that the ligand binding affects the backbone constituents. These results
      were confirmed by docking simulations tested on several SA conformers, which
      showed that ALKSEBEA bound on several sites on SA via pi-pi or pi-cation
      interactions and that the ligand reaches other binding sites, where aromatic and
      basic residues as well as the backbone residues are involved.

PMID- 22973845
TI  - Evaluation and comparison of the ability of online available prediction programs
      to predict true linear B-cell epitopes.
AB  - This work deals with the use of predictors to identify useful B-cell linear
      epitopes to develop immunoassays. Experimental techniques to meet this goal are
      quite expensive and time consuming. Therefore, we tested 5 free, online
      prediction methods (AAPPred, ABCpred, BcePred, BepiPred and Antigenic) widely
      used for predicting linear epitopes, using the primary structure of the protein
      as the only input. We chose a set of 65 experimentally well documented epitopes
      obtained by the most reliable experimental techniques as our true positive set.
      To compare the quality of the predictor methods we used their positive predictive
      value (PPV), i.e. the proportion of the predicted epitopes that are true,
      experimentally confirmed epitopes, in relation to all the epitopes predicted. We
      conclude that AAPPred and ABCpred yield the best results as compared with the
      other programs and with a random prediction procedure. Our results also indicate
      that considering the consensual epitopes predicted by several programs does not
      improve the PPV.

PMID- 22973846
TI  - Role of cation-pi interactions in the structural stability of bacterial adhesins.
AB  - Attachment to host cell surfaces is a crucial step in bacterial infections. This
      step is mediated by important virulence factors termed adhesins which are protein
      in nature. Non-covalent interactions play an important role in the structural
      stability of protein molecules. In the present study, the roles played by cation
      pi interactions in the adhesion proteins of Gram negative bacilli, Gram negative
      cocci and Gram positive cocci are systematically analyzed. There are significant
      differences in the pattern of interactions and environmental preferences like
      secondary structure, solvent accessibility, and stabilization centers for the
      amino acid residues which are involved in interactions. Among the cationic
      residues the role of Arg is significant in Gram negative group, while in the case
      of Gram positive cocci the contribution from Lys is found to be important. These
      results might be useful for understanding the stability patterns of adhesins in
      different groups of pathogenic bacteria.

PMID- 22973847
TI  - Characterizing the functional similarity of enzymes with high co-citation in
      interaction networks.
AB  - New methods for reliable quantitative analysis of biological network data are in
      high demand in today's bioinformatics and systems biology. Here we demonstrate
      the applicability of the co-citation, developed earlier for the analysis of
      scientific literature for finding functionally similar nodes in protein-protein
      interaction networks in several model organisms. We prove the power of our
      approach in a novel way: the predicted closely related enzymes are compared to
      the closeness of their enzyme commission (EC) numbers, therefore we can
      numerically evaluate our prediction method. We have found clear correspondence
      between related enzymatic functions and high co-citation of proteins in
      interaction networks.

PMID- 22973848
TI  - Sequence-specific 1H-NMR assignment and determination of the secondary structure
      of hainantoxin-III from the spider Ornithoctonus hainana.
AB  - Hainantoxin-III (HNTX-III) purified from the venom of the spider Ornithoctonus
      hainana is a novel neurotoxin preferentially inhibiting tetrodotoxin-sensitive
      voltage-gated sodium channels in rat dorsal root ganglion cells. The structure of
      this toxin in aqueous solution was investigated using 2-D 1H-NMR techniques. The
      complete sequencespecific assignments of proton resonances in the 1H-NMR spectra
      were obtained by analyzing a series of 2-D spectra, including DQF-COSY, TOCSY and
      NOESY spectra, in H2O or D2O. All the backbone protons and more than 95% of the
      side-chain protons have been assigned by dalphaN, dbetaN, and dNN connectivities
      in NOESY spectrum. Furthermore, the secondary structure of HNTX-III was
      identified from NMR data. It consists mainly of a short triple-stranded
      antiparallel beta-sheet formed by Asp7 to Cys9, Tyr21 to Ser23, and Lys27 to
      Val30. Because HNTX-III shares high sequence identity (>70%) with HWTX-I and HNTX
      I, we proposed that they all share a structural scaffold known as the inhibitor
      cystine knot architectural motif. This study provides a basis for the further
      determination of the solution conformation of HNTX-III.

PMID- 22973850
TI  - Molecular cloning, expression and characterization of the porcine beta defensin 2
      in E. coli.
AB  - Porcine beta defensin 2(pBD2)is a cationic 37-amino acid antimicrobial peptide
      with disulfide bonds. Synthetic pBD2 had broad antimicrobial activity against
      pathogenic bacteria, and thus pBD2 could be a good candidate as a bactericidal
      agent for pigs. This study reported the successful recombinant expression of pBD2
      in Escherichia coli and analysis of its antimicrobial activity, its hemolytic
      activity, salt-tolerance and thermal stability as well. The pBD2 gene, obtained
      by RT-PCR using the tongue total RNA as a template and cloned into pET30a
      expression vector, was transformed into E. coli BL21 (DE3) plysS. The recombinant
      pBD2 was expressed after induction by IPTG and purified by His tag affinity
      column with 95% purity. The recombinant pBD2 exhibited antimicrobial activity
      against both Gram-positive S. aureus and Gram-negative E. coli including the
      multi-resistant E. coli. The minimum inhibitory concentration (MIC) of
      recombinant pBD2 against tested bacteria was 10 MUg/mL, and the recombinant pBD2
      could kill 50% E. coli at 14.39 MUg/mL and S. aureus at 21.1 MUg/mL. In addition,
      pBD2 showed low hemolytic activity, salt-tolerance and thermal stability, the
      properties would be important for its application in practice.

PMID- 22973849
TI  - Functional and structural analysis of the conserved EFhd2 protein.
AB  - EFhd2 is a novel protein conserved from C. elegans to H. sapiens. This novel
      protein was originally identified in cells of the immune and central nervous
      systems. However, it is most abundant in the central nervous system, where it has
      been found associated with pathological forms of the microtubule-associated
      protein tau. The physiological or pathological roles of EFhd2 are poorly
      understood. In this study, a functional and structural analysis was carried to
      characterize the molecular requirements for EFhd2's calcium binding activity. The
      results showed that mutations of a conserved aspartate on either EF-hand motif
      disrupted the calcium binding activity, indicating that these motifs work in pair
      as a functional calcium binding domain. Furthermore, characterization of an
      identified single-nucleotide polymorphisms (SNP) that introduced a missense
      mutation indicates the importance of a conserved phenylalanine on EFhd2 calcium
      binding activity. Structural analysis revealed that EFhd2 is predominantly
      composed of alpha helix and random coil structures and that this novel protein is
      thermostable. EFhd2's thermo stability depends on its N-terminus. In the absence
      of the N-terminus, calcium binding restored EFhd2's thermal stability. Overall,
      these studies contribute to our understanding on EFhd2 functional and structural
      properties, and introduce it into the family of canonical EF-hand domain
      containing proteins.

PMID- 22973851
TI  - Identification of imperative enzymes by differential protein expression in
      Picrorhiza kurroa under metabolite accumulating and non-accumulating conditions.
AB  - Picrorhiza kurroa, an endangered medicinal plant found in the North-Western
      Himalayan region has a number of medicinal properties due to the presence of
      metabolites picroside-I and picroside-II. It is used in various herbal
      formulations like Picroliv, Livokin, Picrolax, Livomap, Tefroliv etc. Review of
      literature revealed that no information is available as of today on the proteome
      analysis of Picrorhiza kurroa. Hence, we aim to analyse the difference in
      proteome of Picrorhiza kurroa in response to ~ 17 times higher content of
      picroside-I at 15 degrees C as compared to its content at 25 degrees C. Thus,
      differential protein expression was studied. Densitometry analysis of SDS-PAGE
      gels of samples under two differential conditions of temperature revealed the
      presence of distinct set of proteins under picroside-I accumulating (15 degrees
      C) versus non-accumulating (25 degrees C) conditions. Mass spectrometric analysis
      of these proteins using MALDI-TOF MS followed by protein identification using
      database search on MASCOT search engine gave interesting results. The significant
      proteins identified were NAD(P)H-quinone oxidoreductase subunit K, shikimate
      kinase, ribulose bisphosphate carboxylase small chain and fructokinase fragment.
      Hence, these findings throw light on the involvement of these enzymes in the
      crucial physiological processes of Picrorhiza kurroa and can provide an insight
      into the biosynthesis of picrosides and other secondary metabolites.

PMID- 22973852
TI  - Treatment of opportunistic infections prior to HAART initiation does not affect
      immune reconstitution in HIV-infected patients.
AB  - In patients receiving highly active antiretroviral therapy (HAART), increase of
      naive T-cell production, as measured by T-cell receptor rearrangement excision
      circles (TRECs), is an indicator of immune reconstitution. Our objective was to
      assess whether treating opportunistic infections (OIs) prior to HAART initiation
      affects CD4 T-cells recovery and TRECs in patients on HAART. HIV-infected
      patients presenting no OIs or treated OIs were prospectively enrolled prior to
      HAART initiation and followed-up over 12 months of HAART. CD4 T-cells and TRECs
      were measured at baseline, 6 and 12 months HAART and compared between patients
      presenting no OIs and those with treated OIs. Univariate and multivariate
      logistic regression models were used to identify potential factors associated
      with low TREC increase after 12 months HAART. Forty-four HIV-infected patients,
      31 presenting no OIs and 13 with treated OIs at HAART initiation were enrolled.
      Patients presenting no OIs tended to have higher CD4 T-cell gain than those with
      treated OIs (151 vs 89 cells/MUL; p = 0.05) after 6 months HAART but not after 12
      months HAART (120 vs 149 cells/MUL; p = 0.84). Among patients presenting no OIs,
      TREC levels significantly increased from baseline through 12 months HAART while
      among those with treated OIs, there was a trend for increase only after 12
      months. Our study indicates that treatment of OIs prior to HAART does not lead to
      impaired CD4 T-cells recovery and thymic outputs.

PMID- 22973854
TI  - The personal experience of partners of individuals with motor neuron disease.
AB  - Most research on partners' experiences of living with a person with MND is
      questionnaire-based with no qualitative study focusing on the period between
      diagnosis and end-of-life care. This study aimed to provide an in-depth
      qualitative exploration of the experience of living with, and caring for, a
      partner with MND.   Semi-structured interviews were conducted with eight
      individuals, and transcripts analysed from an interpretative phenomenological
      perspective. Two main themes were derived. 'Impact on life' included having
      concern for partner's safety, having social restrictions, being continually
      tired, struggling with anger and frustration, loss of intimacy and uncertainty
      around the future; while 'Adjusting to the situation' included trying to be
      strong, retaining a sense of normality, appreciation of specialist services,
      adopting a problem-solving approach, living day to day and ability to remain
      positive. In conclusion, experiences of stress and loss are illustrated in this
      sample of partners of those with MND, and it is suggested both these aspects
      should be integrated into understanding of carers' experiences. Carers appear to
      inhibit their grief in order to appear strong. Greater understanding of the
      consequences of this would help in providing appropriate emotional support.

PMID- 22973855
TI  - Effects of aging, planning, and interruption on complex prospective memory.
AB  - This study examined the effects of aging, planning, and interruption on complex
      prospective memory (PM) using a 2 x 2 x 2 between-subjects design. Participants
      were 80 younger adults (65 females) aged 18-33 years and 80 older adults (70
      females) aged 60-75 years. They were randomly allocated to four conditions (viz.,
      no interruption and no planning, interruption but no planning, planning but no
      interruption, and both planning and interruption) and asked to undertake three PM
      tasks (time-, event-, and activity-based) while performing an ongoing task (viz.,
      recipe checking and identification) in a simulated home environment. Younger
      adults were found to perform significantly better than older adults on time- and
      event-based PM. The opportunity to plan for five minutes was found to improve
      performances on all three types of PM. Unexpected, external interruptions, on the
      other hand, were found to reduce performance for time-based PM. Interestingly,
      planning was found to significantly improve the performance of older adults on
      time-based PM and to a level similar to that of younger adults. Results of the
      study have clarified the independent and interactive effects of the three
      variables on PM and have implications for understanding and enhancing this type
      of memory.

PMID- 22973856
TI  - Rapid oxalate determination in blood and synthetic urine using a newly developed
      oxometer.
AB  - Blood and urine oxalate determinations have been limited to the laboratory
      setting because of complex sample storage and processing methods as well as the
      need for color spectrophotometry and ion chromatography. We hypothesized that
      glucometer test strips, impregnated with glucose oxidase and dyes that measure
      secondary hydrogen peroxide production, could be infused with oxalate oxidase and
      produce enhanced color changes in the presence of oxalate. By increasing the
      amount of sodium oxalate in fresh blood, we found that glucometer-measured
      oxalate increased on a linear scale. In addition, oxalate levels in synthetic
      urine could be measured using a visual scale, suggesting that strip dwell time or
      oxalate/oxalate oxidase concentrations could be manipulated to enhance optimal
      sensitivity. Although further testing is necessary, this simple, first-generation
      oxometer may eventually allow point of care testing in the home or office,
      empowering patients with oxalate-based medical conditions and giving healthcare
      providers real-time oxalate feedback.

PMID- 22973857
TI  - Complete endoscopic closure (clipping) of a large esophageal perforation after
      pneumatic dilation in a patient with achalasia.
AB  - The risk of esophageal perforation following endoscopic balloon dilation for
      achalasia is in the range of 1%-5%, with a mortality rate of 1%-20%. Perforations
      need to be recognized early, and, if reasonable, an immediate endoscopic repair
      should be pursued quickly. Herein, we report a case of successful endoscopic
      closure by clipping of a large iatrogenic perforation in a patient with
      achalasia. An 80-year-old woman with achalasia was admitted to our institution to
      undergo pneumatic dilation. A 40-mm balloon dilator with inflation pressure of 20
      psi was used for 2 minutes as usual. During the procedure, the patient had a
      transient bradycardia. Endoscopic control showed a 2-cm rupture of the distal
      esophagus. Prompt endoscopic repair of the perforation by endoclips (n=6) was
      then attempted, followed by conservative management by total parenteral nutrition
      and intravenous antibiotics. Endoscopic clipping completely closed the esophageal
      perforation. The patient was given oral nutrition 10 days later without any
      complications. Six months after discharge from the hospital, the patient was
      healthy and free of dysphagia. Endoscopy showed complete healing of the
      esophageal mucosa without luminal stenosis. This report highlights that prompt
      endoscopic clipping is a useful means to close a large esophageal perforation
      caused by pneumatic dilation.

PMID- 22973853
TI  - Substance abuse, HIV-1 and hepatitis.
AB  - During the course of human immunodeficiency virus type 1 (HIV-1) disease, the
      virus has been shown to effectively escape the immune response with the
      subsequent establishment of latent viral reservoirs in specific cell populations
      within the peripheral blood (PB) and associated lymphoid tissues, bone marrow
      (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and
      C viruses (HBV and HCV), are known to share similar routes of transmission,
      including intravenous drug use, blood transfusions, sexual intercourse, and
      perinatal exposure. Substance abuse, including the use of opioids and cocaine, is
      a significant risk factor for exposure to HIV-1 and the development of acquired
      immune deficiency syndrome, as well as HBV and HCV exposure, infection, and
      disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be
      impacted by chronic substance abuse during the course of disease. HIV- 1 impacts
      the natural course of HBV and HCV infection by accelerating the progression of
      HBV/HCV-associated liver disease toward end-stage cirrhosis and quantitative
      depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 is
      also associated with increased mortality when compared to either infection alone.
      This review focuses on the impact of substance abuse and coinfection with HBV and
      HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to
      viral pathogenesis, disease progression, and the associated immune response
      during the course of this complex interplay. The impact of HIV-1 and substance
      abuse on hepatitis virus-induced disease is also a focal point.

PMID- 22973858
TI  - A novel procedure for introducing a large gauze into the corporeal cavity by
      using a slim trocar (the Tornado gauze procedure).
AB  - INTRODUCTION: When a large gauze is needed during a single-incision surgery or
      reduced port surgery using slim (5-mm) trocars, the operation needs to be
      interrupted to introduce the gauze via an incision or to change to a large
      trocar. We describe here a novel procedure for introducing a large gauze into the
      corporeal cavity by using a slim trocar, called the "Tornado gauze procedure"
      (TGP). MATERIALS AND METHODS: Commercially packed Trox((r)) (Osaki Medical,
      Nagoya, Japan) gauze (30*150 mm, 4-ply) and a specially ordered precision
      stainless steel tube (Smart introducer; Kinugawa Factory, Kyoto, Japan) are used
      for the TGP. The gauze is screwed into the Smart introducer. When the surgeon
      needs a gauze, a Smart introducer with a gauze is set into the 5-mm trocar; then,
      the 5-mm grasper is used to push the gauze into the corporeal cavity with small
      screwing-in movements. The gauze is also gently removed from the corporeal cavity
      through a 5-mm trocar. RESULTS: This procedure efficiently and safely introduced
      the gauze for hemostasis, blunt dissection, suction filtering, and organ
      retraction without interrupting the pneumoperitoneum to introduce the gauze in
      single-incision laparoscopic cholecystectomy, transabdominal preperitoneal hernia
      repairs, and appendectomy, with good visualization and adequate working space.
      The rhythm of surgery remains undisturbed with the use of the TGP, even in a high
      risk and high-stress situation. The port's valves were not disabled during
      surgery, and no procedure-related complications were reported. CONCLUSIONS: TGP
      is expected to be helpful to surgeons and enhance the safety of laparoscopic
      surgeries involving the use of slim trocars.

PMID- 22973859
TI  - Insights into pi-conjugated small molecule neat films and blends as determined
      through photoconductivity.
AB  - Spectrally dependent steady-state photoconductivity is a convenient method to
      gain insight into the charge generation and transport processes within a given
      material. In this work, we report on the photoconductive response of solution
      processed neat films and blends of the fullerene, PC(71)BM, and the donor
      acceptor small-molecule, p-DTS(PTTh(2))(2), as function of the processing
      additive, diiodooctance (DIO). The results, when considered in the context of
      their structural, optical, and electronic properties give insight into the
      dominant carrier generation and charge transport mechanisms in each of these
      molecular systems.

PMID- 22973860
TI  - Variability in photocoagulation treatment of diabetic macular oedema.
AB  - PURPOSE: To establish whether differences in the assessment of diabetic macular
      oedema (DME) with either optical coherence tomography (OCT) or stereoscopic
      biomicroscopy lead to variability in the photocoagulation treatment of DME.
      METHODS: The differences in the assessment of DME with either OCT or stereoscopic
      biomicroscopy were analysed by calculating the surface areas and the overlap of
      retinal thickening. Photocoagulation treatment plans of retinal specialists were
      compared by evaluating the number and location of planned laser spots. RESULTS:
      The threshold for and dosage of photocoagulation differ depending upon whether
      the basis of retinal thickness diagnosis is clinical observation or OCT. The
      overlap in laser spot location based on the assessment of DME with OCT or
      biomicroscopy averages 51%. Among retinal specialists, the treatment plans
      differed in the laser spot count by six- to 11-fold. CONCLUSION: Diabetic macular
      oedema photocoagulation treatment threshold and dosage of laser spots differ
      depending on whether thickness assessments are based on stereoscopic slit-lamp
      biomicroscopy or OCT. In addition, retinal specialists differed in the number and
      placement of planned laser spots even when given identical information concerning
      DME and treatable lesions. This variability in the photocoagulation treatment of
      DME could lead to differences in patient outcome and laser study results.

PMID- 22973861
TI  - Burden of stroke in Cambodia.
AB  - In Cambodia, stroke is not ranked among the top 10 leading causes of death, but
      infectious disease are among the top three leading causes of death. This finding
      could be attributed to a lack of awareness among Cambodians of the signs and
      symptoms of stroke or to poor reporting, incomplete data, lack of neurologists
      and neurosurgeons, or low accessibility to the hospitals. The only study of
      stroke in Cambodia is the Prevalence of Non-Communicable Disease Risk Factors in
      Cambodia survey, which identified several stroke-related risk factors in the
      population. Tobacco chewing or smoking is the main risk factor for stroke in
      Cambodia. Traditional therapies, such as oyt pleung (moxibustion) and jup
      (cupping), are widely practiced for stroke rehabilitation. In Cambodia, there are
      few neurologists and few important equipment, such as magnetic resonance imaging
      machines and computed tomography scanners. The Cambodian government should
      cooperate with the World Health Organization and the United Nations Children's
      Fund to attract foreign expertise and technologies to treat stroke patients. 

PMID- 22973862
TI  - Intracoronary injection of drugs to treat no--reflow phenomenon and
      microcirculatory dysfunction.
AB  - In a variant proportion of patients presenting with chest pain and
      electrocardiographic changes characteristic for ST - elevation myocardial
      infarction, percutaneous coronary intervention achieves epicardial coronary
      artery reperfusion but not the myocardial reperfusion (ranging from 5% to 50%).
      Furthermore, prolonged myocardial ischemia often breaks down the coronary
      microvasculature and the flow to the infarct myocardium may seem to be markedly
      reduced. This condition is known as no reflow - phenomenon. The no reflow -
      phenomenon is associated with an increased incidence of malignant ventricular
      arrhythmias, heart failure and 30-days mortality. In the recent years in
      literature, several articles (subsequently discussed in the present review) have
      been published and made relevant to the study of the pathophysiology regarding no
      reflow - phenomenon. This knowledge has assisted in the development of new
      treatment strategies, such as prophylactic use of vasodilators, mechanical
      devices and drugs inhibiting platelet. The review has focused on the current
      literature about intra - coronary injection of drugs to treat no - reflow and
      microvascular dysfunction.

PMID- 22973863
TI  - Risk factors for the incidence of dengue virus infection in preschool children.
AB  - OBJECTIVE: To estimate the seroincidence of dengue in children living in
      Salvador, Bahia, Brazil and to evaluate the factors associated. METHODS:   A
      prospective serological survey was carried out in a sample of children 0-3 years
      of age. A multilevel logistic model was used to identify the determinants of
      seroincidence. RESULTS: The seroprevalence of dengue was 26.6% in the 625
      children evaluated. A second survey detected an incidence of 33.2%. Multilevel
      logistic regression showed a statistically significant association between the
      seroincidence of dengue and age and the premises index. CONCLUSION: In Salvador,
      the dengue virus is in active circulation during early childhood; consequently,
      children have heterotypic antibodies and run a high risk of developing dengue
      haemorrhagic fever, because the sequence and intensity of the three dengue virus
      serotypes currently circulating in this city are very similar to those that were
      circulating in Rio de Janeiro, Brazil, in 2008. Therefore, the authors strongly
      recommend that the health authorities in cities with a similar epidemiological
      scenario be aware of this risk and implement improvements in health care,
      particularly targeting the paediatric age groups. In addition, information should
      be provided to the population and actions should be implemented to combat this
      vector.

PMID- 22973865
TI  - A new ontology (structured hierarchy) of human developmental anatomy for the
      first 7 weeks (Carnegie stages 1-20).
AB  - This paper describes a new ontology of human developmental anatomy covering the
      first 49 days [Carnegie stages (CS)1-20], primarily structured around the parts
      of organ systems and their development. The ontology includes more than 2000
      anatomical entities (AEs) that range from the whole embryo, through organ systems
      and organ parts down to simple or leaf tissues (groups of cells with the same
      morphological phenotype), as well as features such as cavities. Each AE has
      assigned to it a set of facts of the form <AE><relationship><parent>, with the
      relationships including starts_at and ends_at (CSs), part_of (there can be
      several parents) and is_a (this gives the type of tissue, from an organ system
      down to one of ~ 80 simple tissues predominantly composed of a single cell kind,
      which is also specified). Leaf tissues also have a develops_from link to its
      parent tissue. The ontology includes ~14 000 such facts, which are mainly from
      the literature and an earlier ontology of human developmental anatomy (EHDAA, now
      withdrawn). The relationships enable these facts to be integrated into a single,
      complex hierarchy (or mathematical graph) that was made and can be viewed in the
      OBO-Edit browser (oboedit.org). Each AE has an EHDAA2 ID that may be useful in an
      informatics context, while the ontology as a whole can be used for organizing
      databases of human development. It is also a knowledge resource: a user can trace
      the lineage of any tissue back to the egg, study the changes in cell phenotype
      that occur as a tissue develops, and use the structure to add further (e.g.
      molecular) information. The ontology may be downloaded from www.obofoundry.org.
      Queries and corrections should be sent to j.bard@ed.ac.uk.

PMID- 22973864
TI  - Nanoparticle targeting to neurons in a rat hippocampal slice culture model.
AB  - We have previously shown that CdSe/ZnS core/shell luminescent semiconductor
      nanocrystals or QDs (quantum dots) coated with PEG [poly(ethylene glycol)]
      appended DHLA (dihydrolipoic acid) can bind AcWG(Pal)VKIKKP(9)GGH(6) (Palm1)
      through the histidine residues. The coating on the QD provides colloidal
      stability and this peptide complex uniquely allows the QDs to be taken up by
      cultured cells and readily exit the endosome into the soma. We now show that use
      of a polyampholyte coating [in which the neutral PEG is replaced by the
      negatively heterocharged CL4 (compact ligand)], results in the specific targeting
      of the palmitoylated peptide to neurons in mature rat hippocampal slice cultures.
      There was no noticeable uptake by astrocytes, oligodendrocytes or microglia
      (identified by immunocytochemistry), demonstrating neuronal specificity to the
      overall negatively charged CL4 coating. In addition, EM (electron microscopy)
      images confirm the endosomal egress ability of the Palm1 peptide by showing a
      much more disperse cytosolic distribution of the CL4 QDs conjugated to Palm1
      compared with CL4 QDs alone. This suggests a novel and robust way of delivering
      neurotherapeutics to neurons.

PMID- 22973866
TI  - Do we need authorized orphan drugs when compounded medications are available?
AB  - WHAT IS KNOWN AND OBJECTIVE: Orphan drugs are used to diagnose, prevent or treat
      a rare disease. This Commentary aims to present a number of case studies
      questioning the need for designating compounded medications with a long history
      of effective use, which is well-supported by published clinical evidence.
      COMMENT: Prior to the market introduction of orphan drugs, medication compounding
      was done in our hospital pharmacy for several rare diseases. Examples include
      amifampridine for the treatment of Lambert-Eaton myasthenic syndrome
      (Firdapse((r))), ibuprofen for the treatment of neonatal patent ductus arteriosus
      (Pedea((r))) and zinc acetate for the treatment of Wilson's disease
      (Wilzin((r))). Several 'non-orphan' pharmaceutical products, used off-label for
      the treatment of rare diseases, that became orphan medicinal products include
      Hydrea((r)) for the treatment of sickle-cell syndrome (Siklos((r))) and
      Viagra((r)) for the treatment of pulmonary arterial hypertension (Revatio((r))).
      WHAT IS NEW AND CONCLUSION: In our opinion, as indicated by our examples, a
      better balance should be struck between the development of orphan drugs along the
      recently established regulatory pathways and the pragmatic use of pharmacy
      compounded products and evidence-based off-label use of already available
      commercial products. Societal needs would be best met by focusing orphan drug
      development on rare diseases for which there is a high unmet medical need.

PMID- 22973868
TI  - Chiral self-assembly of designed amphiphiles: optimization for nanotube
      formation.
AB  - Four amphiphiles with L-aspartic acid headgroups (Asp) and a diphenyldiazenyl
      group (Azo) contained within the hydrophobic tails were designed and synthesized
      for self-assembly into helically based nanotubes. The amphiphiles of the form R'
      {4-[(4-alkylphenyl)diazenyl]phenoxy}alkanoyl-L-aspartic acid (where R' is 10 or
      11) varied only in alkyl chain lengths either side of the azo group, having 4, 7,
      or 10 carbon distal chains and 10 or 11 carbon proximal chains (R-Azo-R'-Asp,
      where R denotes the number of carbons in the distal chain and R' denotes the
      number of carbons in the proximal chain). Despite the molecular similarities,
      distinct differences were identified in the chiral order of the structures self
      assembled from hot methanolic aqueous solutions using microscopy and
      spectroscopic analyses. This was reflected in dominant thermodynamic aggregate
      morphologies that ranged from amorphous material for 10-Azo-10-Asp, through
      twisted ribbons (196 +/- 49 nm pitch) for 7-Azo-11-Asp, to the desired helically
      based nanotubes for 4- and 7-Azo-10-Asp (81 +/- 11 and 76 +/- 6 nm diameters,
      respectively). Another key variable in the self-assembly of the amphiphiles was
      the use of a second method to precipitate aggregates from solution at room
      temperature. This method enabled the isolation of thermodynamically unstable and
      key transitional structures. Helical ribbons were precursor structures to the
      nanotubes formed from 4- and 7-Azo-10-Asp as well as the wide, flattened nanotube
      structures (587 +/- 85 nm width) found for 4-Azo-10-Asp. Overall, the results
      highlighted the interplay of influence of the headgroup and the hydrophobic tail
      on self-assembly, providing a basis for future rational design of self-assembling
      amphiphiles.

PMID- 22973867
TI  - The burden and consequences of inherited blood disorders among young children in
      western Kenya.
AB  - Although inherited blood disorders are common among children in many parts of
      Africa, limited data are available about their prevalence or contribution to
      childhood anaemia. We conducted a cross-sectional survey of 858 children aged 6
      35 months who were randomly selected from 60 villages in western Kenya.
      Haemoglobin (Hb), ferritin, malaria, C-reactive protein (CRP) and retinol binding
      protein (RBP) were measured from capillary blood. Using polymerase chain reaction
      (PCR), Hb type, -3.7 kb alpha-globin chain deletion, glucose-6-phosphate
      dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More
      than 2 out of 3 children had at least one measured blood disorder. Sickle cell
      trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children,
      respectively; 38.5% were heterozygotes and 9.6% were homozygotes for alpha(+) 
      thalassaemia. The Hp 2-2 genotype was found in 20.4% of children, whereas 8.2% of
      males and 6.8% of children overall had G6PD deficiency. There were no significant
      differences in the distribution of malaria by the measured blood disorders,
      except among males with G6PD deficiency who had a lower prevalence of clinical
      malaria than males of normal G6PD genotype (P = 0.005). After excluding children
      with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency
      (ferritin < 12 MUg L(-1) ) or vitamin A deficiency (RBP < 0.7 MUg L(-1) ), the
      prevalence of anaemia among those without alpha(+) -thalassaemia (43.0%) remained
      significantly lower than that among children who were either heterozygotes
      (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common
      among pre-school children in western Kenya and are important contributors to
      anaemia.

PMID- 22973869
TI  - Type II papillary histology predicts poor outcome in patients with renal cell
      carcinoma and vena cava thrombus.
AB  - What's known on the subject? and What does the study add? In patients with pRCC,
      the presence of venous tumour thrombus is known to be a predictor of poorer
      outcomes. However, a paucity of data is available regarding the prognostic
      significance of histology in patients with RCC and IVC thrombus. In our series,
      we found that patients with type II pRCC had significantly poorer outcomes when
      compared to those with cRCC. Although the lack of effective treatment for
      patients with metastatic pRCC may have contributed to these adverse outcomes,
      type II papillary histology was independent predictor not only of CSS but also of
      RFS. OBJECTIVE: * To analyze the prognostic impact of papillary histology on
      oncological outcomes in patients with renal cell carcinoma (RCC) and inferior
      vena cava (IVC) thrombus. PATIENTS AND METHODS: * We reviewed the medical records
      of 74 patients who underwent radical nephrectomy and IVC thrombectomy between
      1990 and 2010 for clear cell or papillary RCC. * We compared the
      clinicopathological features and clinical outcomes of 62 patients with clear cell
      RCC (cRCC) and 12 with papillary RCC (pRCC). * All cases of pRCC were subdivided
      into type I or type II. * The prognostic role of papillary histology on
      recurrence-free survival (RFS) and cancer-specific survival (CSS) was estimated
      using Cox's regression models. RESULTS: * Upon reclassification of the pRCC
      subtype, all 12 patients with pRCC had type II tumours. * Patients with type II
      pRCC were significantly younger (P=0.028) and were more probably women (P=0.025)
      than those with cRCC * The 2- and 5-year CSS rates were 81.1% and 53.6% in cRCC
      patients, and 28.1% and 0% in type II pRCC patients, respectively. All eight
      patients with non-metastatic type II pRCC developed disease recurrence at a
      median interval of 6 months after surgery, whereas 25 of 44 (56.8%) patients with
      non-metastatic cRCC experienced such recurrence at a median interval of 10 months
      after surgery. * Patients with type II pRCC showed significantly lower CSS
      (P<0.001) and RFS (P=0.002) than those with cRCC. * On multivariate analysis,
      type II papillary histology was an independent predictor of CSS (hazard ratio,
      3.73; P=0.003) and RFS (hazard ratio, 3.15; P=0.015). CONCLUSIONS: * Type II
      papillary histology appears to be predominant in cases of pRCC with IVC thrombus.
      *  Patients with type II pRCC who presented with IVC thrombus had significantly
      worse outcomes than those with cRCC, and histology is an important prognostic
      factor in patients with RCC and IVC thrombus.

PMID- 22973870
TI  - 'If and when?': the beliefs and experiences of community living staff in
      supporting older people with intellectual disability to know about dying.
AB  - BACKGROUND: The aim of this study was to explore the way in which community
      living staff engaged with people with intellectual disability (ID) about dying
      and death. METHOD: Guided by grounded theory methodology, focus groups and
      individual interviews were conducted with staff who had either no experience with
      client death, experience of a client sudden death, or a client death experience
      which was pre-dated by a period of end-of-life care. RESULTS: While in principle,
      staff unanimously supported the belief that people with ID should know about
      dying, there was limited in-practice engagement with clients about the topic.
      Engagement varied according to staff experience, client capacity to understand
      and the nature of the 'opportunity' to engage. Four 'opportunities' were
      identified: 'when family die', 'incidental opportunities', 'when clients live
      with someone who is dying' and 'when a client is dying'. Despite limited
      engagement by staff, people with ID are regularly exposed to dying and death.
      CONCLUSIONS: People with ID have a fundamental right to know about dying and
      death. Sophisticated staff skills are required to ensure that people with ID can
      meaningfully engage with end-of-life issues as opportunities arise.

PMID- 22973871
TI  - Women's experiences of sex and intimacy after childbirth: making the adjustment
      to motherhood.
AB  - The aim of this study was to explore women's experiences of changes to their
      sexual relationship, sexuality and intimacy, as a result of pregnancy, childbirth
      and parenting. A sub-sample of women was purposively selected from a larger
      prospective pregnancy cohort study of nulliparous women in Melbourne, Australia.
      Eighteen women (including a mixture of parity, birth methods and relationship
      status) were interviewed 2.5-3.5 years after a first birth. Interviews were
      transcribed verbatim and analyzed using interpretive phenomenological analysis.
      Women identified numerous factors affecting sexual and intimate relationships
      including extreme tiredness, changing lifestyles and body image issues, leading
      to changes in libido and intimacy in relationships. Of particular note were
      feelings of guilt and failure women experienced as a result of a lowered libido.
      Finding ways to stay connected - whether through sex, quality time together or
      working as a team - helped women and their partners navigate the transition to
      parenthood. This study demonstrates that pregnancy, childbirth and parenting can
      bring about significant changes to women's experiences of sex and intimacy. Women
      who experience significant reductions in their libido may be vulnerable to
      feelings of guilt and failure, connected with high expectations that they should
      be able to "do it all".

PMID- 22973872
TI  - Lentiviral vectors: a versatile tool to fight cancer.
AB  - Over the years, there has been an exponential increase in the number of gene
      therapy approaches that are under investigation for the treatment of cancer. This
      can be attributed to our growing understanding of the molecular mechanisms that
      contribute to the onset and maintenance of cancer as well as to the development
      of gene delivery vectors. In this review, we will focus on the use of lentiviral
      vectors (LVs) in immuno gene therapy of cancer, as these efficacious gene
      delivery vehicles have come to the fore front because of their many attractive
      features. LVs have been successfully applied to generate potent dendritic cell
      based anti-cancer vaccines and to deliver cancer-specific receptors to T-cells.
      Moreover, LVs are under investigation for the modulation of cancer cells. We will
      describe various strategies of this 'genuine' cancer gene therapy, amongst which
      transfer of suicide genes, modulation of pro- and anti-apoptotic molecules,
      strategies to optimize chemo- and radiotherapy, expression of molecules that
      affect angiogenesis or affect the immunogenicity of tumor cells. These will be
      discussed in view of our current knowledge of tumor immunology. Finally we will
      discuss some important issues and future directions to push the field forward.

PMID- 22973875
TI  - Editorial Comment from Dr Senel to circumcision with a novel disposable device in
      Chinese children: a randomized controlled trial.

PMID- 22973873
TI  - New treatments for influenza.
AB  - Influenza has a long history of causing morbidity and mortality in the human
      population through routine seasonal spread and global pandemics. The high
      mutation rate of the RNA genome of the influenza virus, combined with assortment
      of its multiple genomic segments, promote antigenic diversity and new subtypes,
      allowing the virus to evade vaccines and become resistant to antiviral drugs.
      There is thus a continuing need for new anti-influenza therapy using novel
      targets and creative strategies. In this review, we summarize prospective future
      therapeutic regimens based on recent molecular and genomic discoveries.

PMID- 22973874
TI  - Improving the effectiveness of electronic health record-based referral processes.
AB  - Electronic health records are increasingly being used to facilitate referral
      communication in the outpatient setting. However, despite support by technology,
      referral communication between primary care providers and specialists is often
      unsatisfactory and is unable to eliminate care delays. This may be in part due to
      lack of attention to how information and communication technology fits within the
      social environment of health care. Making electronic referral communication
      effective requires a multifaceted "socio-technical" approach. Using an 8
      dimensional socio-technical model for health information technology as a
      framework, we describe ten recommendations that represent good clinical practices
      to design, develop, implement, improve, and monitor electronic referral
      communication in the outpatient setting. These recommendations were developed on
      the basis of our previous work, current literature, sound clinical practice, and
      a systems-based approach to understanding and implementing health information
      technology solutions. Recommendations are relevant to system designers,
      practicing clinicians, and other stakeholders considering use of electronic
      health records to support referral communication.

PMID- 22973877
TI  - Botanical nematicides: a review.
AB  - Despite the uselfuness of nematicidal compounds in agricultural practices, some
      serious concerns are raised today about their excessive use leading to
      enhancement of biodegradation mechanisms in soil expressed as lack of efficacy
      under field conditions and resistance development. Moreover, the phase-out of
      methyl bromide has led to the need for a valid alternative to organophosporous
      and carbamate compounds, such us fosthiazate, fenamiphos, oxamyl, and aldicarb.
      In the past years, intregated pest management strategies have been practised
      worldwide to maximize crop production while maintaining and contributing to
      agriculture sustainability. Biopesticides and specifically bionematicides
      constitute a desirable component of pest management technology and practices.
      Particularly, in the frame of our ongoing research on natural nematicides of
      botanical origin, we have reviewed the international bibliography for candidate
      nematicidal compounds. We report herein the nematicidal activity of plant
      metabolites on the basis of their chemical characteristics and structure. 

PMID- 22973876
TI  - Alterations of leptin in the course of inflammation and severe sepsis.
AB  - BACKGROUND: The adipokine leptin regulates energy expenditure, vascular function,
      bone and cartilage growth as well as the immune system and systemic inflammatory
      response. Several activating effects towards T cells, monocytes, endothelium
      cells and cytokine production have been reported suggesting a protective role of
      leptin in the setting of an acute systemic inflammation. However, the
      pathophysiological role of leptin during severe sepsis is currently not
      elucidated in detail. This study aims to investigate leptin expression in
      cultured human adipocytes within an inflammatory model and in patients suffering
      from severe sepsis and evaluates treatment effects of drotrecogin alpha
      (activated) (DAA), the recombinant form of human activated protein C. METHODS: In
      an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on
      leptin mRNA expression was evaluated. Synthesis of mRNA was measured by
      quantitative polymerase chain reaction (qPCR). Additionally, supernatants of
      these adipocytes as well as serum levels of adiponectin were measured in blood of
      104 severe septic patients by ELISA-method. 26 patients were treated with DAA
      (DAA+), 78 patients were not treated with DAA (DAA-). RESULTS: Stimulation of
      human adipocytes with TNF alpha over 6 and 24 hours resulted in a significant
      decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated
      controls (p < 0.05). Leptin levels of supernatants of adipocyte culture decreased
      by 25% and 23% (p < 0.05) after incubation with TNF alpha after 6 and 24 hours.
      Incubation with DAA at 50 ng/ml DAA and 5 MUg/ml doubled mRNA expression
      significantly at 24 hours (p < 0.05) but not at 6 hours. From day 1 to day 3 of
      sepsis, leptin levels increased in DAA+ compared to DAA- patients (p<0.10).
      CONCLUSIONS: Leptin appears to be involved in the pathogenesis of a systemic
      inflammatory response during sepsis. Administration of DAA significantly
      increased leptin expression. The specific mechanism or even benefit of DAA
      towards leptin needs further ongoing research.

PMID- 22973878
TI  - Thermal transport in functionalized graphene.
AB  - We investigate the effects of two-dimensional (2D) periodic patterns of
      functional groups on the thermal transport in a graphene monolayer by employing
      molecular and lattice dynamics simulations. Our calculations show that the use of
      patterned 2D shapes on graphene reduces the room temperature thermal
      conductivity, by as much as 40 times lower than that of the pristine monolayer,
      due to a combination of boundary and clamping effects. Lattice dynamics
      calculations elucidate the correlation between this large reduction in thermal
      conductivity and two dynamical properties of the main heat carrying phonon modes:
      (1) decreased phonon lifetimes by an order of magnitude due to scattering, and
      (2) direction-dependent group velocities arising from phonon confinement. Taken
      together, these results suggest that patterned graphene nanoroads provide a
      method for tuning the thermal conductivity of graphene without the introduction
      of defects in the lattice, opening an important possibility for thermoelectric
      applications.

PMID- 22973880
TI  - Themed issue: plans, norms, motivation, and cheating a little - the curious case
      of healthy eating.

PMID- 22973879
TI  - A hypoallergenic variant of the major birch pollen allergen shows distinct
      characteristics in antigen processing and T-cell activation.
AB  - BACKGROUND: BM4 is a novel genetically engineered variant of the major birch
      pollen allergen Bet v 1 that lacks the typical Bet v 1-like fold and displays
      negligible IgE-binding but strong T cell-activating capacity. The aim of this
      study was to elucidate possible differences between BM4 and Bet v 1 in
      internalization, antigen processing, and presentation. METHODS: Proliferative
      responses to BM4 and Bet v 1 of peripheral blood mononuclear cells and Bet v 1
      specific T-cell clones were compared. Fluorescently labeled BM4 and Bet v 1 were
      used to study surface binding, endocytosis, and intracellular degradation by
      monocyte-derived DC (mdDC). Both proteins were digested by endolysosomal extracts
      of mdDC. BM4- and Bet v 1-pulsed mdDC were employed to assess the kinetics of
      activation of Bet v 1-specific T-cell clones and the polarization of naive T
      cells. RESULTS: BM4 displayed a significantly stronger T cell-activating capacity
      than Bet v 1. Furthermore, BM4 showed increased surface binding and
      internalization as well as faster endolysosomal degradation compared with Bet v
      1. BM4-pulsed mdDC induced enhanced proliferative responses at earlier time
      points in Bet v 1-specific T-cell clones and promoted less IL-5 production in T
      cells than Bet v 1-pulsed mdDC. CONCLUSION: The loss of the Bet v 1-fold changes
      the protein's interaction with the human immune system at the level of antigen
      presenting cells resulting in altered T-cell responses. By combining low IgE
      binding with strong and modulating T cell-activating capacity, BM4 represents a
      highly interesting candidate for specific immunotherapy of birch pollen allergy.

PMID- 22973881
TI  - One-pot sequential direct C-H bond arylation of azoles catalyzed by
      [Pd(phen)2](PF6)2: synthetic methods for triarylated azoles.
AB  - Synthetic methods for triarylated azoles containing three different aryl groups
      via one-pot sequential multiple C-H bond arylations are described. The one-pot
      sequential diarylation of C5-monoarylated azoles was achieved by the simple
      sequential addition of two different aryl iodides with a [Pd(phen)(2)]PF(6)
      catalytic system. The one-pot triarylation of N-methylimidazole was achieved by
      the combination of a previously reported Pd(OAc)(2)-P(2-furyl)(3) system and the
      present [Pd(phen)(2)]PF(6) system. In this case, portionwise addition of aryl
      halide, base and the catalyst in the final step significantly improved the
      overall yield of the desired triarylated product. These protocols led to
      triarylated azoles without a loss of efficiency compared to the corresponding
      previously reported stepwise syntheses via direct C-H bond arylation.

PMID- 22973883
TI  - Understanding the dissolution of alpha-zein in aqueous ethanol and acetic acid
      solutions.
AB  - Zein is a corn prolamin that has broad industrial applications because of its
      unique physical properties. Currently, the high cost of extraction and
      purification, which is directly related to the dispersion of zein in different
      solvents, is the major bottleneck of the zein industry. Solution behaviors of
      zein have been studied for a long time. However, the physical nature of zein in
      different solvents remains unclear. In this study, small-angle X-ray scattering
      (SAXS), static light scattering (SLS), and rheology were combined to study the
      structure and protein-solvent interaction of alpha-zein in both acetic acid and
      aqueous ethanol solutions. We found that the like-dissolve-like rule, the partial
      unfolding, and the protonation of zein are all critical to understanding the
      solution behaviors. Zein holds an elongated conformation (i.e., prolate
      ellipsoid) in all solutions, as revealed from SAXS data. There is an "aging
      effect" for zein in aqueous ethanol solutions, as evidenced by the transition of
      Newtonian rheological profiles for fresh zein solutions to the non-Newtonian
      shear thinning behavior for zein solutions after storage at room temperature for
      24 h. Such shear thinning behavior becomes more pronounced for zein solutions at
      higher concentrations. The SLS results clearly show that acetic acid is a better
      solvent to dissolve zein than aqueous ethanol solution, as supported by a more
      negative second virial coefficient. This is majorly caused by the protonation of
      the protein, which was further verified by the dissolution of zein in water (a
      nonsolvent for zein) with the addition of acids.

PMID- 22973884
TI  - Anti-disease therapy for malaria - 'resistance proof'?
AB  - Antimalarial drugs have in the past fallen prey to resistance and this problem is
      likely to continue in the future. One approach to developing drugs that might be
      less prone to resistance might be to target the disease rather than the parasite
      itself. The rationale for this idea, which has been somewhat developed in
      antibacterial chemotherapy, is that drugs that can alleviate disease pathogenesis
      while not compromising the survival, growth or transmission of the pathogen
      should not exert selective pressure that would encourage the emergence and spread
      of resistance. This review considers (concentrating on possible interventions at
      the parasite level) whether such 'anti-disease' therapy could be developed for
      severe Plasmodium falciparum malaria, and if so whether it might be less prone to
      resistance. Several anti-adhesive treatments, aiming to reduce the tissue
      sequestration of P. falciparum-parasitised erythrocytes that is associated with
      cerebral malaria and other complications, have been investigated as 'adjunctive'
      therapies. These therapies are however unlikely to be 'resistance proof' because
      sequestration appears to enhance parasite survival in the host. Severe malarial
      anaemia is another potentially fatal complication of malaria that results not
      only from lysis of host erythrocytes by intracellular parasites but to a greater
      extent from lysis of unparasitised erythrocytes and impaired erythropoiesis. The
      possibility of therapy interfering with the last of these processes, which may be
      more 'resistance proof', is discussed in detail.

PMID- 22973882
TI  - Ceramide sphingolipid signaling mediates Tumor Necrosis Factor (TNF)-dependent
      toxicity via caspase signaling in dopaminergic neurons.
AB  - BACKGROUND: Dopaminergic (DA) neurons in the ventral midbrain selectively
      degenerate in Parkinson's disease (PD) in part because their oxidative
      environment in the substantia nigra (SN) may render them vulnerable to
      neuroinflammatory stimuli. Chronic inhibition of soluble Tumor Necrosis Factor
      (TNF) with dominant-negative TNF inhibitors protects DA neurons in rat models of
      parkinsonism, yet the molecular mechanisms and pathway(s) that mediate TNF
      toxicity remain(s) to be clearly identified. Here we investigated the
      contribution of ceramide sphingolipid signaling in TNF-dependent toxicity.
      RESULTS: Ceramide dose-dependently reduced the viability of DA neuroblastoma
      cells and primary DA neurons and pharmacological inhibition of sphingomyelinases
      (SMases) with three different inhibitors during TNF treatment afforded
      significant neuroprotection by attenuating increased endoplasmic reticulum (ER)
      stress, loss of mitochondrial membrane potential, caspase-3 activation and
      decreases in Akt phosphorylation. Using lipidomics mass spectrometry we confirmed
      that TNF treatment not only promotes generation of ceramide, but also leads to
      accumulation of several atypical deoxy-sphingoid bases (DSBs). Exposure of DA
      neuroblastoma cells to atypical DSBs in the micromolar range reduced cell
      viability and inhibited neurite outgrowth and branching in primary DA neurons,
      suggesting that TNF-induced de novo synthesis of atypical DSBs may be a secondary
      mechanism involved in mediating its neurotoxicity in DA neurons. CONCLUSIONS: We
      conclude that TNF/TNFR1-dependent activation of SMases generates ceramide and
      sphingolipid species that promote degeneration and caspase-dependent cell death
      of DA neurons. Ceramide and atypical DSBs may represent novel drug targets for
      development of neuroprotective strategies that can delay or attenuate the
      progressive loss of nigral DA neurons in patients with PD.

PMID- 22973885
TI  - Antimalarial drug resistance and early drug discovery.
AB  - The malaria parasite has been allowed to get perilously close to winning the
      upper hand in the race between new drugs and resistance development. Today, just
      one class of drugs is left to avoid a public health disaster of global
      proportions, the artemisinins, and even they are showing signs of a possible
      impending failure. Rational approaches to overcoming antimalarial drug resistance
      are difficult for several reasons. Resistance mechanisms are varied and
      imperfectly known across Plasmodium species and often there is not a good
      correlation between in vitro drug susceptibility, molecular markers of resistance
      and therapeutic failure, except for antimalarials acting on well defined
      molecular targets such as atovaquone and the antifolates. Drugs with more complex
      modes of action are expected to have correspondingly complex resistance
      mechanisms. Molecular markers of resistance for the most widely used quinoline,
      chloroquine, have been identified, but they are not applicable to all parasite
      species and perhaps not even to all strains. Analyses of drug resistance in vitro
      are also limited by the fact that only one malaria parasite species, Plasmodium
      falciparum, is amenable to long term culture. Nevertheless, reducing the risk of
      premature therapeutic failure due to quick resistance emergence needs to be
      considered from the earliest stages of drug discovery. In the present review we
      attempt to summarize the main mechanisms of resistance to current antimalarials
      and provide information on already available assays to estimate the propensity of
      a new molecule to select for resistant parasites.

PMID- 22973886
TI  - Targeting host factors to circumvent anti-malarial drug resistance.
AB  - The most common treatments for infectious diseases target the invading pathogen.
      The efficacy of such an approach may, however, be countered by the possibility of
      the development of resistance to a pharmacophore, through mutation(s) in pathogen
      molecules required for activity. Given the fact that pathogens exploit host
      factors in order to grow in an otherwise hostile environment, one possible way to
      circumvent the emergence of resistance is to develop drugs that target non
      essential host factors hijacked by the pathogen, rather than the pathogen's own
      molecules. Such solutions are already being developed for various viral and
      bacterial pathogens, but much less has been achieved with infections caused by
      protozoan parasites, as is the case of Plasmodium. Here, we highlight recent
      progress in host target-based anti-viral and anti-bacterial approaches and
      discuss possible host targets that may be used for anti-malarial interventions.
      Host molecules that play a role during either the liver or the blood stage of
      Plasmodium infection are outlined and their potential merits as anti-malarial
      targets are discussed.

PMID- 22973887
TI  - The need for new antimalarial drugs less prone to resistance.
AB  - Although reports of antimalarial drug resistance emerged as early as 1910 from
      South America, the first event that really had a major impact on malaria control
      and drug development was the emergence of chloroquine resistance in the 2nd half
      of the 20th century. The appearance of resistance to chloroquine has marked the
      onset of a race between the development of ever new generations of antimalarial
      drugs and the emergence of resistance to these antimalarials, finally culminating
      in the emergence of clinical artemisinin resistance which was first reported in
      2008. The potentially devastating impact of resistance to a drug that has been
      adopted as the first line drug for the treatment of uncomplicated falciparum
      malaria by virtually all malaria control programs throughout the malaria-endemic
      world, and for which there currently is no successor in sight should it truly
      fall victim to widespread drug resistance, calls for strategies to extend the
      useful life spans of currently available antimalarial drugs while at the same
      time stepping up efforts to develop novel combination therapies not based on
      artemisinins.

PMID- 22973889
TI  - Editorial: antimalarial drug discovery and design in the era of resistance.

PMID- 22973890
TI  - Effects of a self-care promoting problem-based learning programme in people with
      rheumatic diseases: a randomized controlled study.
AB  - AIM: To evaluate the effects of a self-care promoting problem-based learning
      programme for people with rheumatic diseases in terms of health-related quality
      of life, empowerment, and self-care ability. BACKGROUND: Individuals with
      rheumatoid arthritis express a great need for education and support in adapting
      to the disease, but the average qualities of studies about patient education
      interventions are not high. There is no evidence of long-term benefits of patient
      education. DESIGN: Randomized controlled trial. METHODS: A randomized controlled
      design was selected with test at baseline, 1-week and 6-month post-interventions
      after completed the 1-year programme. The tests consisted of validity and
      reliability tested instruments. The participants were randomly assigned in spring
      2009 to either the experimental group (n = 54) or the control group (n = 148).
      The programme was running alongside the standard care the participants received
      at a rheumatology unit. Parametric and non-parametric tests were used in the
      analyses. RESULTS: The participants in the experimental group had statistically
      significant stronger empowerment after participation in the self-care promoting
      problem-based learning programme compared with the control group, at the 6-month
      post-intervention. Approximately, two-thirds of the participants in the
      experimental group stated that they had implemented lifestyle changes due to the
      programme. CONCLUSION: The self-care promoting problem-based learning programme
      enabled people with rheumatic diseases to improve their empowerment compared with
      the control group. It is important to continue to develop problem-based learning
      in patient education to find the very best way to use this pedagogical method in
      rheumatology care.

PMID- 22973888
TI  - Plasmodium drug targets outside the genetic control of the parasite.
AB  - Drug development often seeks to find "magic bullets" which target microbiologic
      proteins while not affecting host proteins. Paul Ehrlich tested methylene blue as
      an antimalarial but this dye was not superior to quinine. Many successful
      antimalarial therapies are "magic shotguns" which target many Plasmodium pathways
      with little interference in host metabolism. Two malaria drug classes, the 8-
      aminoquinolines and the artemisinins interact with cytochrome P450s and host iron
      protoporphyrin IX or iron, respectively, to generate toxic metabolites and/or
      radicals, which kill the parasite by interference with many proteins. The non 8
      amino antimalarial quinolines like quinine or piperaquine bind heme to inhibit
      the process of heme crystallization, which results in multiple enzyme inhibition
      and membrane dysfunction. The quinolines and artemisinins are rapidly
      parasiticidal in contrast to metal chelators, which have a slower parasite
      clearance rate with higher drug concentrations. Iron chelators interfere with the
      artemisinins but otherwise represent a strategy of targeting multiple enzymes
      containing iron. Interest has been revived in antineoplastic drugs that target
      DNA metabolism as antimalarials. Specific drug targeting or investigation of the
      innate immunity directed to the more permeable trophozoite or schizont infected
      erythrocyte membrane has been under explored. Novel drug classes in the
      antimalarial development pipeline which either target multiple proteins or
      unchangeable cellular targets will slow the pace of drug resistance acquisition.

PMID- 22973891
TI  - Familial amyloid polyneuropathy associated with the novel transthyretin variant
      Arg34Gly.
AB  - We report a 57-year-old man with pathognomonic bilateral vitreo-lenticular
      amyloid opacities (pseudopodia lentis) in whom a novel transthyretin (TTR)
      mutation was identified. The patient presented due to bilateral floaters. The
      vitreous cavities of both eyes showed course, fibrilar opacities attached to the
      posterior lens surface with pseudopodia. There was a history of bilateral carpal
      tunnel syndrome. Nerve conduction studies showed upper and lower limb axonal
      polyneuropathy. Magnetic resonance imaging of the brain and spinal cord, renal
      and cardiac function were normal. Vitreous and conjunctival biopsies confirmed
      the diagnosis of TTR-related amyloidosis. Genetic analysis of exon 2 of the TTR
      gene revealed that the patient was heterozygous for a single nucleotide
      substitution c.160 A>G, resulting in replacement of arginine with glycine at
      position 34 of the mature protein (Arg34Gly). Five years later the patient
      developed increasing sensory and motor neuropathy of both lower limbs, and
      neovascular glaucoma in one eye. We hypothesize that the reason for his
      neovascular glaucoma was retinal ischaemia secondary to amyloid retinal
      vasculopathy.

PMID- 22973892
TI  - Extracellular conversion of adiponectin hexamers into trimers.
AB  - Adiponectin is an adipocyte-secreted hormone that exists as trimers, hexamers and
      larger species collectively referred to as HMW (high-molecular-weight)
      adiponectin. Whether hexamers or HMW adiponectin serve as precursors for trimers
      outside the circulation is currently unknown. Here, we demonstrate that
      adiponectin trimers can be generated from larger oligomers secreted from primary
      rat adipose cells or differentiated 3T3-L1 adipocytes. Purified hexameric, but
      not HMW, adiponectin converted into trimers in conditioned media separated from
      3T3-L1 adipocytes or, more efficiently, when enclosed in the dialysis membrane in
      the presence of adipocytes. Several lines of evidence indicate that the
      conversion is mediated by an extracellular redox system. First, N-terminal
      epitope-tagged hexamers converted into trimers without proteolytic removal of the
      tag. Secondly, appearance of trimers was associated with conversion of disulfide
      bonded dimers into monomers. Thirdly, thiol-reactive agents inhibited conversion
      into trimers. Consistent with a redox-based mechanism, purified hexamers
      reductively converted into trimers in defined glutathione redox buffer with
      reduction potential typically found in the extracellular environment while the
      HMW adiponectin remained stable. In addition, conversion of hexamers into trimers
      was enhanced by NADPH, but not by NADP+. Collectively, these data strongly
      suggest the presence of an extracellular redox system capable of converting
      adiponectin oligomers.

PMID- 22973893
TI  - Potent inhibitors of human organic anion transporters 1 and 3 from clinical drug
      libraries: discovery and molecular characterization.
AB  - Transporter-mediated drug-drug interactions in the kidney dramatically influence
      the pharmacokinetics and other clinical effects of drugs. Human organic anion
      transporters 1 (hOAT1) and 3 (hOAT3) are the major transporters in the
      basolateral membrane of kidney proximal tubules, mediating the rate-limiting step
      in the elimination of a broad spectrum of drugs. In the present study, we
      screened two clinical drug libraries against hOAT1 and hOAT3. Of the 727
      compounds screened, 92 compounds inhibited hOAT1 and 262 compounds inhibited
      hOAT3. When prioritized based on the peak unbound plasma concentrations of these
      compounds, three inhibitors for hOAT1 and seven inhibitors for hOAT3 were
      subsequently identified with high inhibitory potency (>95%). Computational
      analyses revealed that inhibitors and noninhibitors can be differentiated from
      each other on the basis of several physicochemical features, including number of
      hydrogen-bond donors, number of rotatable bonds, and topological polar surface
      area (TPSA) for hOAT1; and molecular weight, number of hydrogen-bond donors and
      acceptors, TPSA, partition coefficient (log P(7.4)), and polarizability for
      hOAT3. Pharmacophore modeling identified two common structural features
      associated with inhibitors for hOAT1 and hOAT3, viz., an anionic hydrogen-bond
      acceptor atom, and an aromatic center separated by ~5.7 A. Such model provides
      mechanistic insights for predicting new OAT inhibitors.

PMID- 22973894
TI  - Deep Trichophyton rubrum infection presenting with umbilicated papulonodules in a
      cardiac transplant recipient.

PMID- 22973895
TI  - L1CAM and its cell-surface mutants: new mechanisms and effects relevant to the
      physiology and pathology of neural cells.
AB  - The L1 syndrome, a genetic disease that affects 1/30 000 newborn males, is
      sustained by numerous missense mutations of L1 cell adhesion molecule (L1CAM), an
      adhesion surface protein active also in transmembrane signaling, essential for
      the development and function of neurons. To investigate the cell biology of
      L1CAM, we employed a high RE1-silencing transcription (factor) clone of the
      pheochromocytoma PC12 line, defective in L1CAM expression and neurite outgrowth.
      The clone was transfected with wild-type L1CAM and four missense, disease
      inducing point mutants encoding proteins distributed to the cell surface. The
      mutant-expressing cells, defective in adhesion to extracellular matrix proteins
      and in migration, exhibited unchanged proliferation. The nerve growth factor
      (NGF)-induced neurite outgrowth was re-established in defective clone cells
      transfected with the wild-type and the H210Q and I219T L1CAMs mutants, but not in
      the others. The stimulated outgrowth was confirmed in a second defective PC12
      clone over-expressing the NGF receptor TrkA, treated with NGF and/or a
      recombinant L1CAM chimera. These results revealed a new function of L1CAM, a
      positive, robust and dose-dependent modulation of the TrkA receptor activated
      spontaneously or by NGF. The variable effects observed with the different L1CAM
      mutants suggest that this function contributes to the marked heterogeneity of
      symptoms and severity observed in the patients affected by the L1 syndrome.

PMID- 22973896
TI  - Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute
      stroke patients: a systematic review and meta-analysis.
AB  - It has been questioned whether patients with cerebral microbleeds are at a
      greater risk for the development of symptomatic intracerebral hemorrhage
      following thrombolytic therapy in the management of acute ischemic stroke. Thus
      far, observational studies have not shown a statistically significant increased
      risk; however, these have been limited by small sample size. The aim is to better
      quantify the risk of postthrombolysis intracerebral hemorrhage in patients with
      acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A
      systematic review of controlled studies investigating the presence of microbleeds
      on magnetic resonance imaging as a risk factor for intracerebral hemorrhage
      following thrombolysis in acute stroke patients was conducted. A random effects
      model meta-analysis was performed. In pooled analysis of five studies totaling
      790 participants, the prevalence of microbleeds was 17%. The presence of
      microbleeds revealed a trend toward an increased risk of postthrombolysis
      symptomatic intracerebral hemorrhage [odds ratio: 1.98 (95% confidence interval,
      0.90 to 4.35; P = 0.09), I(2)  = 0%]. Adjusted analysis minimizing potential bias
      resulted in an increased absolute risk of 4.6% for the development of symptomatic
      intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2.29
      (95% confidence interval, 1.01 to 5.17), I(2)  = 0%] reaching borderline
      significance (P = 0.05). A significant relationship between increasing microbleed
      burden and symptomatic intracerebral hemorrhage (P = 0.0015) was observed.
      Isolated analysis of studies using exclusively intravenous tissue plasminogen
      activator was insignificant. Our data suggest that patients with cerebral
      microbleeds are at increased risk for symptomatic intracerebral hemorrhage
      following thrombolysis for acute ischemic stroke. However, current data are
      insufficient to justify withholding thrombolytic therapy from acute ischemic
      stroke patients solely of the basis of cerebral microbleed presence.

PMID- 22973897
TI  - Micropercutaneous nephrolithotomy in the treatment of moderate-size renal
      calculi.
AB  - PURPOSE: We present our initial experience with microperc in patients with
      moderate-size renal calculi. PATIENTS AND METHODS: A retrospective analysis of 30
      patients (male 14, female 16) with moderate-size (1-3 cm) kidney stones who
      underwent microperc between August 2011 and July 2012 was performed. The
      demographic values, perioperative and postoperative measures including age, stone
      size and location, body mass index, operative and fluoroscopy time, hemoglobin
      decrease, success and complication rates were prospectively recorded into a
      patient entry system. RESULTS: The average stone size was 17.9+/-5.0 mm (10-30
      mm). The mean age of the patients was 41.5+/-18.2 years (range 3-69 years). The
      duration of the operation was calculated as 63.5+/-36.8 minutes (range 20-200
      min). Mean fluoroscopic screening time was 150.5+/-90.4 seconds (range 45-360
      seconds). The patients were discharged after a mean hospitalization period of
      35.5+/-18.6 hours (range 14-96 hours). An overall success rate of 93% (including
      10% of insignificant residual fragment rate) was achieved. In the follow-up,
      residual stone fragments were detected in two (7%) patients. Conversion to
      miniperc was necessitated in three (10%) patients. The mean hemoglobin drop was
      found to be 1.1+/-0.8 mg/dL (range 0-2.8 mg/dL). Complications were observed in
      five (13.3%) patients. CONCLUSIONS: Our initial results provide that microperc is
      a feasible, safe, and efficacious treatment modality for moderate-size kidney
      stones as well as small ones with its minimally invasive nature. Technical
      refinements are needed to achieve better results and overcome the limitations of
      technique.

PMID- 22973898
TI  - Type II papillary histology predicts poor outcome in patients with renal cell
      carcinoma and vena cava thrombus.

PMID- 22973899
TI  - An international review of the patterns and determinants of health service
      utilisation by adult cancer survivors.
AB  - BACKGROUND: There is a need to review factors related to health service
      utilisation by the increasing number of cancer survivors in order to inform care
      planning and the organisation and delivery of services. METHODS: Studies were
      identified via systematic searches of Medline, PsycINFO, CINAHL, Social Science
      Citation Index and the SEER-MEDICARE library. Methodological quality was assessed
      using STROBE; and the Andersen Behavioural Model was used as a framework to
      structure, organise and analyse the results of the review. RESULTS: Younger,
      white cancer survivors were most likely to receive follow-up screening,
      preventive care, visit their physician, utilise professional mental health
      services and least likely to be hospitalised. Utilisation rates of other health
      professionals such as physiotherapists were low. Only studies of health service
      use conducted in the USA investigated the role of type of health insurance and
      ethnicity. There appeared to be disparate service use among US samples in terms
      of ethnicity and socio-demographic status, regardless of type of health insurance
      provision s- this may be explained by underlying differences in health-seeking
      behaviours. Overall, use of follow-up care appeared to be lower than expected and
      barriers existed for particular groups of cancer survivors. CONCLUSIONS: Studies
      focussed on the use of a specific type of service rather than adopting a whole
      system approach and future health services research should address this
      shortcoming. Overall, there is a need to improve access to care for all cancer
      survivors. Studies were predominantly US-based focussing mainly on breast or
      colorectal cancer. Thus, the generalisability of findings to other health-care
      systems and cancer sites is unclear. The Andersen Behavioural Model provided an
      appropriate framework for studying and understanding health service use among
      cancer survivors. The active involvement of physicians and use of personalised
      care plans are required in order to ensure that post-treatment needs and
      recommendations for care are met.

PMID- 22973900
TI  - Individual support planning: perceptions and expectations of people with
      intellectual disabilities in The Netherlands.
AB  - BACKGROUND: According to Dutch jurisdiction, individual support plans (ISP)
      should register the mutual agreements between a person with intellectual
      disabilities (ID) and a professional service organisation with respect to the
      support that will be provided. In planning for support, active involvement of
      both parties is necessary. The current study focuses on the perceptions and
      experiences of Dutch persons with ID with respect to their involvement in their
      ISP. METHOD: Data were gathered through semi-structured interviews with 61 people
      with mild to moderate ID. Participants were recruited in 23 Dutch service
      provider organisations. A systematic qualitative analysis was performed on the
      interview transcripts. RESULTS: Although persons with ID are present at their ISP
      meeting, active client involvement in developing, executing and evaluating the
      ISP is not common practice. Issues of accessibility and lack of control over the
      process and content of ISP hamper effective involvement of people with ID.
      CONCLUSIONS: The study raises questions concerning ISP practices in the
      Netherlands. The question needs to be addressed as to how to facilitate active
      involvement of people with ID in planning for support. The results further
      suggest that support organisations perceive an ISP rather as a formal document to
      comply with bureaucratic rules than as an instrument of empowerment to enhance
      control of persons with ID over their own lives.

PMID- 22973901
TI  - The economic burden of hypertension in rural south-west China.
AB  - OBJECTIVE: To estimate the economic burden of hypertension in a given year in
      rural Yunnan Province of China, including direct, indirect and intangible costs.
      METHODS: A prevalence-based cost-of-illness method was used to estimate the
      economic burden of hypertension. Data on participants' demographic
      characteristics, inpatient hospitalisation expenditures, outpatient visit
      expenditures, self-medication costs and indirect costs related to hypertension
      were collected from a cross-sectional health examination and questionnaire
      survey, involving 9396 consenting individuals aged >= 18 years and 3500
      households. Blood pressure (BP) levels were determined from the average of three
      BP measurements. Years of life lost (YLL) because of hypertension was estimated
      using medical death certificates. RESULTS: The overall prevalence of and YLL/1000
      population because of hypertension was 24.8% and 1.5 years for the survey
      population, respectively. Mean unit direct medical costs, direct non-medical
      costs, morbidity costs, mortality costs, intangible costs and cost of illness
      were estimated to be $ 467.2, $ 20.1, $ 23.5, $ 8265.1, $ 417.4 and $ 9393.3,
      respectively. The total cost of hypertension was estimated to be $ 231.7 million.
      Direct costs represented the largest component of economic cost of hypertension.
      On average, males had higher overall direct, indirect and intangible costs of
      hypertension than females. Both indirect and intangible costs decreased with age,
      whereas direct costs increased with age. The incidence of household catastrophic
      health payment and household impoverishment because of hypertension was 8.9% and
      4.1%, respectively. CONCLUSIONS: Hypertension inflicts a considerable economic
      burden upon individual households and society as a whole in Yunnan Province,
      China.

PMID- 22973902
TI  - Physiological vitreous changes may contribute to the pathogenesis of macular
      degeneration.

PMID- 22973903
TI  - Single nucleotide polymorphisms in thymic stromal lymphopoietin gene are not
      associated with allergic rhinitis susceptibility in Chinese subjects.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived
      cytokine, implicated in the development and progression of allergic diseases.
      Recent studies have demonstrated significantly increased expression and synthesis
      of TSLPin nasal mucosa of patients with allergic rhinitis (AR), compared with
      nonallergic control subjects. Also, there is significant correlation between the
      level of TSLP mRNA and symptom severity in AR patients. In this study, we
      investigated whether polymorphisms in the TSLP gene were associated with
      increased risk of AR in the Chinese population. METHODS: In a candidate gene
      association study, we tested 11 single nucleotide polymorphisms (SNPs) in the
      TSLP gene in 368 AR and 325 control adult Han Chinese subjects from Beijing. The
      11 SNPs were selected from the Chinese HapMap genotyping dataset to ensure
      complete genetic coverage. AR was established by questionnaire and clinical
      examination, and blood was drawn from all subjects for DNA extraction. The PLINK
      software package was used to perform statistical testing. RESULTS: In the single
      locus analysis of AR risk, no significant differences in allele and genotype
      frequencies were found between AR and control subjects. Further logistic
      regression analyses adjusted for age and gender also failed to reveal significant
      associations between AR and the selected SNPs. Similarly, analysis stratified by
      gender, and haplotype or diplotype did not reveal any association with AR risk.
      CONCLUSION: Although TSLP presents itself as a good candidate for contributing to
      allergy, this study failed to find an association between specific SNPs in the
      TSLP gene and AR susceptibility in the Han Chinese population.

PMID- 22973904
TI  - Vascular endothelial growth factor expression following ischemic conditioning of
      the gastric conduit.
AB  - The partial devascularization of the stomach, necessary for esophageal
      reconstruction with a gastric conduit, impairs microcirculation in the
      anastomotic region of the gastric fundus. Ischemic conditioning of the gastric
      tube is considered as a possible approach to improve microcirculation in the
      gastric mucosa. The aim of this study was to investigate whether ischemic
      conditioning induces neo-angiogenesis in the gastric fundus by expression of
      vascular endothelial growth factor (VEGF). Twenty patients with an esophageal
      carcinoma scheduled for esophagectomy and gastric reconstruction were included.
      To compare VEGF expression before and after ischemic conditioning, preoperative
      endoscopic biopsies were taken from the gastric fundus. The surgical procedure
      consisted of two separate steps, the complete gastric mobilization including
      partial devascularization of the stomach and after a delay of 4-5 days high
      transthoracic esophagectomy with intrathoracic gastric reconstruction (Ivor-Lewis
      procedure). The second tissue sample was obtained from the donut of the stapled
      esophagogastrostomy. For further work-up, preoperative biopsies and the gastric
      donuts were fixed in liquid nitrogen. Preoperative and intraoperative VEGF
      expression was measured by quantitative real-time reverse transcription
      polymerase chain reaction (VEGF*100/beta-actin) and results were compared using
      Wilcoxon test for paired samples. In all 40 specimens, a distinct expression of
      VEGF could be detected. Comparing the level of VEGF expression of the
      preoperative biopsies and postoperative tissue sample, no significant difference
      could be demonstrated following ischemic conditioning. In this model of ischemic
      conditioning with delayed reconstruction of 4-5 days, no induction of neo
      angiogenesis could be demonstrated by measurement of VEGF expression. 

PMID- 22973905
TI  - Study on metal-induced reactions of alpha-diazocarbonyl glucosides.
AB  - Conversions of diazocarbonyl carbohydrate compounds catalyzed by a series of
      rhodium and copper catalysts in conventional heating or microwave conditions were
      investigated. C-H insertion product was obtained in the presence of
      Rh(2)(OAc)(4). Intermolecular reactions rather than intramolecular reactions
      occurred in the presence of copper catalysts.

PMID- 22973906
TI  - Honey bee (Apis mellifera) venom induces AIM2 inflammasome activation in human
      keratinocytes.
AB  - BACKGROUND: Following allergen exposure, cytokines and other pro-inflammatory
      signals play an important role in the immunological cascade leading to allergic
      sensitization. Inflammasomes sense exogenous and endogenous danger signals and
      trigger IL-1beta and IL-18 activation which in turn shape Th2 responses. Honey
      bee venom (BV) allergies are very common; however, the local inflammatory cascade
      leading to the initiation of allergic sensitization is poorly understood. In this
      study, the local inflammatory cascades in skin after exposure to BV were
      investigated. METHODS: The mechanisms of inflammasome activation in human skin
      and in cultured keratinocytes upon BV exposure were analyzed by ELISA, Western
      blot, flow cytometry, siRNA techniques, and immunofluorescence. RESULTS: In an ex
      vivo bee sting model, BV induced IL-1beta release suggesting the activation of
      inflammasomes. Indeed, in cultured keratinocytes, the BV component melittin
      triggered IL-1beta and IL-18 release via the AIM2 inflammasome. AIM2 is a
      cytosolic DNA receptor, and mitochondrial as well as genomic DNA was detected in
      the cytosol of melittin-treated keratinocytes as triggers of inflammasome
      activation. As a mechanism, melittin mediated destruction of mitochondrial
      membranes leading to the leakage of mitochondrial DNA into the cytosolic
      compartment. CONCLUSION: These data suggest that upon BV exposure, keratinocytes
      are involved in an innate immune response by the activation of the AIM2
      inflammasome and subsequent IL-1beta and IL-18 release triggered by endogenous
      DNA. As IL-1beta and IL-18 are involved in Th2- and IgE-mediated immune
      reactions, these results could add to the understanding of the role of the tissue
      microenvironment to subsequent allergic responses.

PMID- 22973907
TI  - Temporal regulation of HTLV-2 expression in infected cell lines and patients:
      evidence for distinct expression kinetics with nuclear accumulation of APH-2
      mRNA.
AB  - BACKGROUND: Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are
      delta retroviruses with similar genetic organization. Although both viruses
      immortalize T-cells in vitro, they exhibit distinct pathogenic potential in vivo.
      To search for possible differences in its expression strategy with respect to
      HTLV-1, we investigated the pattern of HTLV-2 expression in infected cell lines
      and peripheral blood mononuclear cells (PBMCs) from infected patients using
      splice site-specific quantitative RT-PCR. FINDINGS: A novel alternative splice
      acceptor site for exon 2 was identified; its usage in env transcripts was found
      to be subtype-specific. Time-course analysis revealed a two-phase expression
      kinetics in an infected cell line and in PBMCs of two of the three patients
      examined; this pattern was reminiscent of HTLV-1. In addition, the minus-strand
      APH2 transcript was mainly detected in the nucleus, a feature that was similar to
      its HTLV-1 orthologue HBZ. In contrast to HTLV-1, expression of the mRNA encoding
      the main regulatory proteins Tax and Rex and that of the mRNAs encoding the p28
      and truncated Rex inhibitors is skewed towards p28/truncated Rex inhibitors in
      HTLV-2. CONCLUSION: Our data suggest a general converging pattern of expression
      of HTLV-2 and HTLV-1 and highlight peculiar differences in the expression of
      regulatory proteins that might influence the pathobiology of these viruses.

PMID- 22973909
TI  - Tension among business, government, and health care.

PMID- 22973910
TI  - Population pharmacokinetics of oxycodone in patients with cancer-related pain.
AB  - Oxycodone is an opioid widely prescribed to cancer patients for pain relief.
      However, the pharmacokinetics of oxycodone has not been sufficiently examined.
      Therefore the aim of this work was to study population pharmacokinetics of
      oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone
      samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population
      pharmacokinetics was calculated using the one-compartment model of clearance,
      volume of distribution, bioavailability, absorption constant rate, and lag time.
      An exponential error model was used to determine interindividual variability and
      a relative error model was applied to assess residual variability. Population
      pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 *
      [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) =
      193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual
      variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability
      was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh
      class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5.
      Therefore, it became clear that dose adjustments are essential when treating
      patients with liver dysfunction. These findings suggest that population
      parameters are useful for evaluating pharmacokinetics of oxycodone in patients
      with cancer pain.

PMID- 22973911
TI  - Nasogastric and percutaneous endoscopic gastrostomy tube use in advanced head and
      neck cancer patients: a comparative study.
AB  - To compare the efficacy of percutaneous endoscopic gastrostomy (PEG) and
      nasogastric (NGT) tube administration of enteral nutrition in head and neck
      cancer patients undergoing curative treatment, the authors conducted a
      prospective study to compare nutritional outcomes, complications, and patient
      satisfaction. PEG patients sustained significantly less reduction in nutritional
      parameters, measured at 6 weeks post insertion, as compared with NGT patients.
      There was also a statistically significant difference between the two groups in
      patient's quality of life scores and complications. Comparison could not be done
      at 6 months because all patients were converted to PEG feeding due to the earlier
      findings. The authors conclude that PEG is more efficacious than NGT as a channel
      for nutrition in advanced head and neck cancer patients over a short duration.

PMID- 22973912
TI  - The supply chain of medicinal controlled substances: addressing the Achilles heel
      of drug diversion.
AB  - The escalation of prescription drug abuse in the U.S. has attracted the attention
      of public health and safety officials as well as others puzzled by how such a
      tightly regulated enterprise could so easily be breached by those seeking
      controlled substances for nonmedical use. Prescribers and patients who use,
      misuse, or, in some cases, redistribute or divert these drugs have figured
      prominently in government strategies aimed at addressing this issue. This review
      departs from this paradigm and focuses on wholesale drug distributors, a highly
      efficient and largely behinds-the-scene link in the supply chain of controlled
      substances. By law, distributors are required to identify and report to the Drug
      Enforcement Administration (DEA) orders for controlled substances that are
      suspicious and may indicate drug diversion. Ten cases are examined in which
      distributors were each charged with failing to prevent the diversion of millions
      of doses of controlled substances. Special attention is given to a payment system
      employed by the industry that may encourage this unlawful commerce. Court
      records, agency and industry reports, and other published sources are used to
      document referenced cases and their disposition, and recommendations are offered
      for improving distributors' compliance with the law.

PMID- 22973913
TI  - Distribution of controlled substances in the U.S. supply chain: where does the
      compass point?
AB  - Recent administrative actions taken by the Drug Enforcement Administration (DEA)
      in Florida have prompted an articulate and detailed discussion of the
      pharmaceutical supply chain for controlled substances. Current practices in
      commercial distribution systems may have a partial nexus to the proliferation of
      opioid prescription drug abuse in Florida. No single factor or entity is
      responsible for this abuse proliferation, and there is no intent to harm
      consumers; however, distribution practices are adding risk to public health. This
      commentary extends a discussion on supply chain practices that seem misaligned in
      the promotion of legitimate business objectives and advancing public health.

PMID- 22973914
TI  - Unpredictable absorption of oral opioid medications in a quadriplegic patient
      with chronic enterocutaneous fistulas.
AB  - Although there is an abundance of literature on the acute management of
      enterocutaneous fistulas, there is a paucity of data on the chronic management of
      enterocutaneous fistulas. Their impact on oral pharmacotherapy, including their
      effect on the bioavailability of oral medications, is poorly understood. This
      case describes a 23-year-old quadriplegic male with a complex history of multiple
      abdominal surgeries presented with three persistent enterocutaneous fistulas.
      Diazepam and furosemide were among the patient's oral medications and had
      sufficient bioavailability to show efficacy on anxiety and pedal edema,
      respectively. Conversely, oral oxycodone and methadone were ineffective in
      controlling chronic pain despite high doses and aggressive titration. Due to
      inadequate pain control, the patient supplemented opioid medications with high
      doses of lorazepam and diazepam to augment psychological comfort. A trial of
      subcutaneous morphine successfully produced immediate analgesia, causing a marked
      reduction in benzodiazepine use. Enterocutaneous fistulas may reduce the
      bioavailability of oral medications to various degrees depending upon the
      medication. Further research is needed to elucidate the effect chronic
      enterocutaneous fistulas have on the bioavailability of oral medications. It is
      therefore important for clinicians to question the bioavailability of medications
      in the setting of enterocutaneous fistulas and poor clinical response.

PMID- 22973915
TI  - The association between pain and depression and some determinants of depression
      for the general population of the United States.
AB  - Pain and depression are major reasons for pharmacotherapy, making the
      relationship between these two complaints important in defining optimal
      pharmacotherapy for both. Although the association between the two has been
      documented in the literature, most of the available work only focused on specific
      disease group or patients with certain type of pain. Whether the association
      exists for the general population is still an unsettled issue. The goal of this
      study was to examine the association between pain and depression and explore the
      some determinants of depression using national representative survey data for the
      general population in the United States. This work employed data from Medical
      Expenditure Panel Survey (MEPS) 2009, with people older than 18 were included in
      the study. Ordered logistic regression and generalized ordered logistic
      regression were performed while incorporating complex survey features. Estimation
      results suggested that depression and physical pain were positively associated.
      In addition, individuals with better perceived health, older age, male gender,
      higher family income, and employed were less depressed. Divorced or separated
      marital status was associated with higher depression level. This work fills the
      gap in the literature by using nationally representative survey data set to
      examine the association between physical pain and depression. Levels of physical
      pain and many socioeconomic factors were found significantly associated with
      depression.

PMID- 22973916
TI  - Errors in pain management: a Mexican perspective.
AB  - Over the past three decades, health professionals have recognized that continued
      mismanagement of pain affect approximately one third of all hospitalized patients
      as well as many ambulatory patients. Various measures have been taken to correct
      this problem, including the development of pain management guidelines and
      standards by governments, medical associations, accrediting bodies, and
      international organizations. However, these issues remain problems with no clear
      solution. This commentary reflects the opinions of two practicing Mexican pain
      management physicians on these issues as they pertain to clinicians managing pain
      in Mexico today.

PMID- 22973917
TI  - An island of compassion.
AB  - This narrative describes the experience of a palliative care physician from
      Australia visiting the palliative care service at a cancer hospital in India. The
      place of compassion in an environment of limited resources is discussed.

PMID- 22973918
TI  - A reflective study of symptom management in terminal cancer.
AB  - Perceived experiences of patients are important hallmarks of symptom control not
      only for physical symptoms, but also for the psychological, social, and spiritual
      dimensions. Listening to patients' narratives opens window to diagnosing the
      patients' symptoms. This reflection outlines the importance of this practice in
      managing symptoms of a terminally ill cancer patient.

PMID- 22973919
TI  - When two worlds meet.
AB  - The author is one of four American premedical students traveled to India to spend
      a month with Pallium India (palliumindia.org) to learn about palliative care at
      Trivandrum Institute of Palliative Sciences, in the south Indian state of Kerala.
      The program was arranged by Child Family Health International (cfhi.org). They
      attended classroom sessions and joined the palliative care team during home
      visits and hospital consultations. They learned not just what palliative care is,
      but also how to understand and adapt to another culture. It was shocking to learn
      that all health care expenses are often out-of-pocket for most of the developing
      world and to see the extent of the suffering involved in life-limiting diseases.
      The students saw how the medical professional could adopt a basic and simple
      approach to medicine, acting as a mix of scientist, humanist, and spiritualist.
      She concludes that we in the United States too seem to be learning the value of
      such an approach and to make better use of available resources to improve the
      quality of life of those who are suffering.

PMID- 22973933
TI  - Childhood migraines: symptoms and treatments.
AB  - Questions from patients about pain conditions, analgesic pharmacotherapy, and
      responses from authors are presented to help educate patients and make them more
      effective self-advocates. This article contains a brief description of childhood
      migraines.Topics including symptoms of childhood migraines, age of onset,
      therapies, and suggestions for adults to support children with migraines are
      discussed.

PMID- 22973938
TI  - Costs of end-of-life care.

PMID- 22973940
TI  - Role of catechins in the antioxidant capacity of an active film containing green
      tea, green coffee, and grapefruit extracts.
AB  - The oxygen radical absorbance capacity (ORAC) method was used to characterize the
      antioxidant capacity of natural extracts of green tea, green coffee, and
      grapefruit. These natural extracts were incorporated into a plastic film layer,
      which was subsequently subjected to a free radical gas stream in order to
      determine the antioxidant capacity directly in the active film. The green tea
      extract (GTE) afforded the strongest antioxidant activity. To identify the active
      compounds in the extract, concentration of the diverse catechins in samples were
      determined by HPLC-UV analysis. The results showed that the content of catechins
      in the GTE is around 77% (w/w), the major components being (-)-epigallocatechin
      gallate, (-)-epicatechin gallate, and (-)-epicatechin. A variation in the
      concentration profile of catechins was detected during the oxidation process. The
      chromatographic study demonstrated that (-)-gallocatechin, (-)- epigallocatechin,
      (+)-catechin, and (-)-catechin gallate exhibited the most radical scavenging.

PMID- 22973941
TI  - Preoperative diagnosis of a breast hydatid cyst using fine-needle aspiration
      cytology: a case report and review of the literature.
AB  - INTRODUCTION: A hydatid cyst of the breast is rare and often goes unnoticed by
      mammography and ultrasound. Preoperative diagnosis may be performed using fine
      needle aspiration cytology, which also minimizes the risk of intraoperative
      rupture. CASE PRESENTATION: We report the case of a 70-year-old Spanish woman who
      was diagnosed with a hydatid cyst using fine-needle aspiration cytology before
      surgery. CONCLUSION: Fine-needle aspiration cytology is an accurate and safe
      technique that can allow surgery to be avoided, especially in older patients or
      patients with high surgical risk.

PMID- 22973942
TI  - Near-field scanning optical microscopy enables direct observation of Moire
      effects at the nanometer scale.
AB  - This work reports probing the Moire effect directly at the nanometer scale via
      near-field scanning optical microscopy (NSOM). Periodic metal nanostructures of
      Au and Cu have been produced sequentially using particle lithography, and the
      overlapped regions serve as Moire patterns at nanometer scale. The Moire effect
      in these regions can be directly visualized from NSOM images, from which
      periodicity and structural details are accurately determined. In addition, the
      near-field Moire effect was found to be very sensitive to structural changes,
      such as lateral displacement and/or rotations of the two basic arrays with
      respect to each other. Further, nanostructures of Cu exhibited higher photon
      transmission than Au from NSOM images. Collectively, NSOM enables direct
      visualization of the Moire effect at nanoscale levels, from optical read out, and
      without enhancements or modification of the structures. The results demonstrate
      the feasibility to extend applications of the Moire effect-based techniques to
      nanometer levels.

PMID- 22973943
TI  - Unravelling the structure of protic ionic liquids with theoretical and
      experimental methods: ethyl-, propyl- and butylammonium nitrate explored by Raman
      spectroscopy and DFT calculations.
AB  - We present an analysis of gas-phase structures of small clusters of n
      alkylammonium nitrates (ethyl, propyl, and butyl) together with vibrational Raman
      spectroscopy of their respective liquid phases. The assignment and interpretation
      of the resonant frequencies have been performed by comparison with high-quality
      ab initio (DFT) computations. The theoretical spectra are in excellent agreement
      with the measured ones and allow the interpretation and assignment of almost all
      the spectral features. A careful analysis of the vibrational frequencies and of
      the electronic structure of the compounds has provided additional information on
      various structural features and on the rather complex hydrogen bonding network
      that exists in such compounds. A geometric structure of the short-range local
      arrangement in the bulk phases is also proposed.

PMID- 22973944
TI  - Natural DNA-modified graphene/Pd nanoparticles as highly active catalyst for
      formic acid electro-oxidation and for the Suzuki reaction.
AB  - Natural DNA has been considered as a building block for developing novel
      functional materials. It is abundant, renewable, and biodegradable and has a well
      defined structure and conformation with many unique features, which are difficult
      to find in other polymers. Herein, calf thymus DNA modified graphene/Pd
      nanoparticle (DNA-G-Pd) hybrid materials are constructed for the first time using
      DNA as a mediator, and the prepared DNA-G-Pd hybrid shows high catalytic activity
      for fuel cell formic acid electro-oxidation and for organic Suzuki reaction. The
      main advantages of using DNA are not only because the aromatic nucleobases in DNA
      can interact through pi-pi stacking with graphene basal surface but also because
      they can chelate Pd via dative bonding in such defined sites along the DNA
      lattice. Our results indicate that isolated, homogeneous, and ultrafine spherical
      Pd nanoparticles are densely in situ decorated on DNA-modified graphene surfaces
      with high stability and dispersibility. The prepared DNA-G-Pd hybrid has much
      greater activity and durability for formic acid electro-oxidation than the
      commercial Pd/C catalyst and polyvinylpyrrolidone-mediated graphene/Pd
      nanoparticle (PVP-G-Pd) hybrid used for direct formic acid fuel cells (DFAFCs).
      Besides, the DNA-G-Pd hybrid can also be an efficient and recyclable catalyst for
      the organic Suzuki reaction in aqueous solution under aerobic conditions without
      any preactivation. Since DNA can chelate various transition metal cations, this
      proof-of-concept protocol provides the possibility for the tailored design of
      other novel catalytic materials based on graphene with full exploitation of their
      properties.

PMID- 22973945
TI  - A randomized controlled trial undertaken to test a nurse-led weight management
      and exercise intervention designed for people with serious mental illness who
      take second generation antipsychotics.
AB  - AIM: To test the effect of a nurse-led intervention on weight gain in people with
      serious mental illness prescribed and taking second generation antipsychotic
      medication. BACKGROUND: Weight gain and obesity has reached epidemic proportions
      in the general population with the prevalence of Metabolic Syndrome reaching 20
      25% of the global population. People with serious mental illness are at even
      higher risk, particularly those taking second generation antipsychotic
      medication. DESIGN: An experimental randomized controlled trial was undertaken.
      METHOD: The control group received a 12-week healthy lifestyle booklet. In
      addition to the booklet, the intervention group received weekly nutrition and
      exercise education, exercise sessions, and nurse support. Participants (n = 101)
      were assessed at baseline and 12 weeks. Data were collected between March 2008
      December 2010. Seven outcome measures were used: body measurements included girth
      (cm), weight (kg), height (cm), and body mass index (kg/m(2) ); questionnaires
      included the medication compliance questionnaire, the Drug Attitude Inventory,
      the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical
      Outcomes Study Short Form 36. Differences in primary outcome measures between
      baseline and 12 weeks follow-up were compared between intervention and control
      groups using standard bi-variate statistical tests. The study was conducted
      between 2008-2010. RESULTS: The analysis of outcome measures for the control
      group (n = 50) and intervention group (n = 51) was not statistically significant.
      There was a mean weight change of -0.74 kg at 12 weeks for the intervention group
      (n = 51), while the control group (n = 50) had a mean weight change of -0.17 kg
      at 12 weeks. CONCLUSION: The results were not statistically significant.

PMID- 22973946
TI  - Long-term consequence of elevated thyroglobulin in differentiated thyroid cancer.
AB  - BACKGROUND: Serum thyroglobulin (Tg) is the most sensitive biomarker for
      recurrence of differentiated thyroid cancer (DTC). We have assessed the changing
      pattern of stimulated Tg (sTg) and the clinical course of patients with no
      structural evidence of disease (NSED), based on imaging studies such as neck
      ultrasonography (US), fluorodeoxyglucose positron emission tomography, and/or
      chest computed tomogram (CT). We sought to determine if, in patients with DTC who
      had been treated with bilateral thyroidectomy and remnant ablation with
      radioactive iodine, sTg 1 year (sTg1) after initial treatment and repeated sTg
      measurements, 1-2 years after sTg1, helped predict the long-term outcome with
      respect to structural recurrence and biochemical remission (BR), which is defined
      as sTg <1 ng/mL. METHODS: We retrospectively assessed the records of patients
      with DTC who had been treated with bilateral thyroidectomy and remnant ablation
      with radioactive iodine between 1995 and 2004. The study included 186 patients
      who had NSED with sTg1 >=2 ng/mL and subsequent sTg measurements (sTg2) without
      additional treatment. Patients were classified into three groups based on their
      sTg1 measurements: Group A, 2-4.9 ng/mL; Group B, 5-19.9 ng/mL; and Group C, >=20
      ng/mL. Patients were also classified into two groups based on whether sTg2, 1-2
      years after sTg1, had decreased by >=50% (Group 1) or had either decreased by
      <50% or increased (Group 2). sTg was measured every 1-2 years until structural
      recurrence or BR. RESULTS: Patients remaining in NSED showed a decrease in serial
      sTg. Of patients in Groups A, B, and C, 41%, 17%, and 1%, respectively, achieved
      BR, and there was a significant difference in the BR rate between Groups 1 and 2
      (p<0.001). In patients with structural recurrence, serial sTg generally did not
      decrease from sTg1. There was a significant difference in the recurrence rate
      among Groups A, B, and C (p=0.005) and between Groups 1 and 2 (p<0.001).
      CONCLUSIONS: We found that 41% of patients with sTg1 in the range 2-5 ng/mL
      achieved BR, and that sTg1 and percent change of subsequent sTg were predictive
      of BR. Repeated sTg measurements are useful for predicting patient prognosis in
      patients with DTC.

PMID- 22973947
TI  - Surface molecules on HaCaT keratinocytes after interaction with non-thermal
      atmospheric pressure plasma.
AB  - Non-thermal atmospheric-pressure plasmas have been developed that will be used in
      future for several purposes, e.g. medicine. Living tissues and cells are at the
      focus of plasma treatment, e.g. to improve wound healing, or induce apoptosis and
      growth arrest in tumour cells. Detailed investigations of plasma-cell
      interactions are needed. Cell surface adhesion molecules as integrins, cadherins
      or the EGFR (epidermal growth factor receptor) are of importance in wound healing
      and also for development of cancer metastasis. This study has focused on
      measurement of cell surface molecules on human HaCaT keratinocytes (human adult
      low calcium temperature keratinocytes) promoting adhesion, migration and
      proliferation as one important feature of plasma-cell interactions. HaCaT
      keratinocytes were treated with plasma by a surface dielectric barrier discharge
      in air. Cell surface molecules and induction of intracellular ROS (reactive
      oxygen species) were analysed by flow cytometry 24 h after plasma treatment.
      Besides a reduction of cell viability a significant down-regulation of E-cadherin
      and the EGFR expression occurred. The influence on alpha2- and beta1-integrins
      was less pronounced, and expression of ICAM-1 (intercellular adhesion molecule 1)
      was unaffected. The extent of effects depended on the exposure time of cells to
      the plasma and the treatment regimen. Intracellular level of ROS detected by the
      fluorescent dye H2DCFDA (2',7'-dichlorodihydrofluorescein diacetate) increased by
      plasma treatment, but it was neither dependent on the treatment time nor related
      to the different treatment regimens. Two-dimensional cultures of HaCaT
      keratinocytes appear to be a suitable method of investigating plasma-cell
      interactions.

PMID- 22973948
TI  - Leptin attenuates ischemia-reperfusion injury in the rat liver.
AB  - Leptin is an adipocytokine that reduces ischemic damage in several organs
      including brain and heart. STAT3 activation is a key step for the attainment of
      leptin effects in various tissues. We evaluated the possible effect of leptin on
      liver viability and STAT3 activation, in a rat model of ischemia-reperfusion
      injury. Rat livers, flushed and stored with Belzer solution (4 degrees  C for 24
      h), were warmly reperfused (3.5 ml/min/g liver for 1 h at 37 degrees  C with O(2)
      ) with Krebs-Ringer bicarbonate. Treatment group underwent an identical protocol
      with the adjunct of Leptin (10 ng/ml). Liver effluent was harvested to assess LDH
      and AST output. Liver tissue was used for pSTAT3 expression (western blot and
      immunostaining), optical microscopy, TUNEL, and Cell Death Detection assays. The
      pSTAT3 expression was enhanced by administration of leptin. In parallel, LDH and
      AST output were reduced (P = 0.04 and P = 0.02 for LDH and AST, respectively).
      Optical microscopy, TUNEL, and Cell Death Detection assay results demonstrated
      increased viability in livers treated with leptin in comparison with others
      (Optical microscopy P = 0.02; TUNEL P = 0.01; Cell death Detection assay P =
      0.003). In conclusion, cold storage and reperfusion with leptin reduce liver
      ischemia-reperfusion injury. This effect is associated with an increased
      expression of pSTAT-3.

PMID- 22973949
TI  - Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph
      subcomplex is important for both gamma-secretase assembly and substrate
      recruitment.
AB  - gamma-secretase is a protease complex with at least four components: presenilin,
      nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2
      (Pen-2). In this study, using knockout cell lines and small interfering RNA
      technology, our data demonstrated that the disappeared presenilin 1 C-terminal
      fragment (PS1C) caused by knockdown of pen-2 or knockout of NCT or Aph-1 was
      recovered by the addition of proteasome inhibitors, indicating that Pen-2, as
      well as NCT and Aph-1alpha, is dispensable for presenilin endoproteolysis. Our
      data also demonstrate that the formation of the nicastrin-Aph-1 subcomplex plays
      not only an important role in gamma-secretase complex assembly but also in
      recruiting substrate C-terminal fragment of amyloid precursor protein generated
      by beta-cleavage. Ablating any one component resulted in the instability of other
      components of the gamma-secretase complex, and the presence of all three of the
      other components is required for full maturation of NCT.

PMID- 22973950
TI  - Risk of cardiovascular events and death in the life after aneurysmal subarachnoid
      haemorrhage: a nationwide study.
AB  - BACKGROUND AND AIM: The increased mortality rates of survivors of aneurysmal
      subarachnoid haemorrhage have been attributed to an increased risk of
      cardiovascular events in a registry study in Sweden. Swedish registries have
      however not been validated for subarachnoid haemorrhage and Scandinavian
      incidences of cardiovascular disease differ from that in Western European
      countries. We assessed risks of vascular disease and death in subarachnoid
      haemorrhage survivors in the Netherlands. METHODS: From the Dutch hospital
      discharge register, we identified all patients with subarachnoid haemorrhage
      admission between 1997 and 2008. We determined the accuracy of coding of the
      diagnosis subarachnoid haemorrhage for patients admitted to our centre.
      Conditional on survival of three-months after the subarachnoid haemorrhage, we
      calculated standardized incidence and mortality ratios for fatal or nonfatal
      vascular diseases, vascular death, and all-cause death. Cumulative risks were
      estimated with survival analysis. RESULTS: The diagnosis of nontraumatic
      subarachnoid haemorrhage was correct in 95.4% of 1472 patients. Of 11,263
      admitted subarachnoid haemorrhage patients, 6999 survived more than three-months.
      During follow-up (mean 5.1 years), 874 (12.5%) died. The risks of death were 3.3%
      within one-year, 11.3% within five-years, and 21.5% within 10 years. The
      standardized mortality ratio was 3.4 (95% confidence interval: 3.1 to 3.7) for
      vascular death and 2.2 (95% confidence interval: 2.1 to 2.3) for all-cause death.
      The standardized incidence ratio for fatal or nonfatal vascular diseases was 2.7
      (95% confidence interval: 2.6 to 2.8). CONCLUSIONS: Dutch hospital discharge and
      cause of death registries are a valid source of data for subarachnoid
      haemorrhage, and show that the increased mortality rate in subarachnoid
      haemorrhage survivors is explained by increased risks for vascular diseases and
      death.

PMID- 22973951
TI  - Social network and risk-taking behavior most associated with rapid HIV testing,
      circumcision, and preexposure prophylaxis acceptability among high-risk Indian
      men.
AB  - Indian truck drivers and their younger apprentice drivers are at increased risk
      of HIV infection. We determine network and risk practices associated with
      willingness to adopt HIV prevention interventions currently not being used in
      India: rapid HIV testing, circumcision, and preexposure prophylaxis (PrEP) in
      order to inform the National AIDS Control Program (NACP). Truck drivers and truck
      cleaners were systematically recruited to participate in a social network and
      risk survey in Hyderabad, Southern India. Three separate composite measures of
      acceptability of rapid HIV testing, circumcision, and PrEP acceptability were
      utilized to independently assess the relationship of these prevention
      interventions with risk-practices and social network characteristics. An 89%
      participation rate yielded 1602 truck drivers and truck cleaners with 54.2%
      younger than 30 years of age and 2.8% HIV infected. Twenty-five percent of
      respondents reported sex with female sex workers (FSW) and 5% with men (MSM).
      Rapid testing, circumcision, and PrEP acceptability were 97.4%, 9.1%, and 85.9%,
      respectively. Participants reporting prosocial network characteristics were more
      accepting of rapid testing (adjusted odds ratio [AORs] 3.07-6.71; p<0.05) and
      demonstrated variable PrEP acceptability (AORs 0.08-2.22; p<0.001). Sex with FSWs
      was associated with PrEP acceptability (AOR 4.27; p<0.001); sex with MSM was
      associated with circumcision acceptability only (AOR 2.66; p<0.01). Social
      network factors and risk-practices were associated with novel prevention
      acceptability, but not consistently across intervention type and with variable
      directionality. The NACP will need to consider that intervention uptake may
      likely be most successful when efforts are targeted to individuals with specific
      behavior and social network characteristics.

PMID- 22973952
TI  - Targeting HER receptors in cancer.
AB  - Receptor tyrosine kinases play important roles in animal development and their
      deregulation has been linked to several pathologies, including cancer or
      diabetes. In cancer, the ERBB/HER family of receptors has been shown to
      participate in the pathophysiology of breast, gastric, colorectal, lung and head
      and neck tumors. Activation of HER receptors occurs by receptor-receptor
      interactions facilitated by ligand binding, overexpression or molecular
      alterations of the HER receptors. The best example is the known role of HER2 in
      the tumorigenesis of a proportion of breast tumors. In this review, we will
      describe the biological bases that govern HER receptor activation, and this will
      represent the bases for the explanation of how to target HER receptors in cancer.
      We will discuss the current therapeutic options to target HER receptors, which
      are based on anti-receptor antibodies or small molecule kinase inhibitors. We
      will also describe current clinical applications and future developments of
      agents which target HER receptors. Finally, we will mention mechanism of
      resistance to anti-HER therapies, and will describe options to overcome such
      resistances.

PMID- 22973953
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors: current status and
      future perspectives in the development of novel irreversible inhibitors for the
      treatment of mutant non-small cell lung cancer.
AB  - Conventional chemotherapeutic regimens have reached an efficacy plateau against
      most solid tumors and deal with significant toxicity. Recently, the goal of
      oncologic research to improve outcome and reduce treatment-related side-effects
      has led to the development of novel anticancer treatments targeting specific
      proteins or genes involved in cancer growth and progression. In particular, the
      tyrosine- kinase inhibitors (TKIs) gefitinib and erlotinib targeting the
      epidermal growth factor receptor (EGFR) have been approved for the treatment of
      non-small-cell lung cancer (NSCLC). Their clinical activity has been related to
      different clinical and biological parameters, such as the presence of activating
      mutations in the kinase domain of the target. Disappointingly, their clinical
      efficacy is limited by the development of resistance which is caused in more than
      50% of the cases by the emergence of a secondary point-mutation (T790M) in the
      ATP-binding cleft of EGFR. Several novel EGFR inhibitors, able to covalently bind
      the target and prolong its inactivation, have been developed with the aim to
      overcome such resistance and are evaluated in ongoing clinical studies. However,
      not all clinical outcomes, including tolerability, are explained, and the
      identification/validation of novel biomarkers of sensitivity or resistance to
      such agents is a viable area of research to improve their clinical use. This
      review summarizes the current knowledge on the functional role of activating
      mutations of EGFR, pivotal primary/acquired resistance mechanisms as well as
      clinical data of small molecule EGFR-TKIs, and discusses the future of such
      therapeutic approach in NSCLC.

PMID- 22973954
TI  - Detection and therapeutic implications of c-Met mutations in small cell lung
      cancer and neuroendocrine tumors.
AB  - BACKGROUND: We evaluated the mutation status of c-Met in small cell lung cancer
      (SCLC) and neuroendocrine tumors (NET), for which relatively limited therapeutic
      targets have been explored. MATERIALS AND METHODS: c-Met was re-sequenced using
      cell lines and clinical samples. For in vitro studies, DNA constructs containing
      a juxtamembrane domain (JMD) and tyrosine kinase domain (TKD) were generated.
      Detected mutations were introduced into the construct and effects on c-Met
      phosphorylation and interaction with tyrosine kinase inhibitor drugs BMS777607
      and SU11274 were assessed. RESULTS: 97 specimens were analyzed: 13 SCLC and 2
      pulmonary carcinoid cell lines, 46 SCLC and 36 NET clinical specimens. Mutations
      were only detected in the JMD. No mutations were detected in the TKD. Found
      mutations consisted of the previously reported R988C and T1010I mutations. One
      novel JMD mutation, P996S, was detected in a SCLC specimen. The mutation rate in
      SCLC cell lines was 25% (31% including a derivative cell line), and 6.5% in
      clinical specimens. The mutation rate in NET was 8.3%. In vitro, there were no
      differences between wild type, R988C or T1010I mutants regarding c-Met
      phosphorylation at Y1003, located in the JMD, and at Y1234/1235, located in the
      TKD. BMS777607 and SU11274 were shown to inhibit phosphorylation of c-Met in wild
      type and R988C and T1010I mutants in a similar fashion. CONCLUSIONS: In SCLC and
      neuroendocrine tumors MET mutations are relatively rare. Detected mutations were
      located in the juxtamembrane domain and were of no functional relevance as they
      did not influence c-Met phosphorylation, regardless of TKI treatment.

PMID- 22973955
TI  - Anti-metastatic treatment in colorectal cancer: targeting signaling pathways.
AB  - Colorectal cancer is one of the most common cancers worldwide and one of the
      leading causes of cancer-related death in the Western world. Tumor progression
      towards metastasis affects a large number of patients with colorectal cancer and
      seriously affects their clinical outcome. Therefore, considerable effort has been
      made towards the development of therapeutic strategies that can decrease or
      prevent colorectal cancer metastasis. Standard treatment of metastatic colorectal
      cancer with chemotherapy has been improved in the last 10 years by the addition
      of new targeted agents. The currently used antibodies bevacizumab, cetuximab and
      panitumumab target the VEGF and EGFR signaling pathways, which are crucial for
      tumor progression and metastasis. These antibodies have shown relevant efficacy
      in both first- and second-line treatment of metastatic colorectal cancer.
      Additionally, other signaling pathways, including the Wnt and HGF/Met pathways,
      have a well-established role in colorectal cancer progression and metastasis and
      constitute, therefore, promising targets for new therapeutic approaches. Several
      new drugs targeting these pathways, including different antibodies and small
      molecule tyrosine kinase inhibitors, are currently being developed and tested in
      clinical trials. In this review, we summarize the new developments in this field,
      focusing on the inhibitors that show more promising results for use in colorectal
      cancer patients.

PMID- 22973956
TI  - Inhibition of RET activated pathways: novel strategies for therapeutic
      intervention in human cancers.
AB  - The REarranged during Transfection (RET) proto-oncogene and its activated
      signalling pathways have been shown to play an important role in cancer. RET
      genetic alterations including germline, somatic mutations and gene rearrangements
      have been demonstrated in several solid tumours, and numerous clinical trials
      using multikinase inhibitors containing RET as a target have shown significant
      activity against RET. Sorafenib and sunitinib have been approved for the
      treatment of renal, hepatocellular, gastrointestinal and pancreatic neuoendocrine
      carcinomas. Vandetanib has recently been approved for the treatment of
      unresectable locally advanced or metastatic medullary thyroid carcinomas. Novel
      genomic rearrangements and RET signalling interactions are now being studied in a
      variety of tumours and will provide the basis for new therapeutic strategies.
      Combination or sequential targeted therapies that are based on solid preclinical
      data regarding the inhibition of RET-mediated parallel or different -signalling
      pathways will likely be more effective.

PMID- 22973957
TI  - Modulation of sensitivity to antitumor agents by targeting the MAPK survival
      pathway.
AB  - Mitogen-activated protein kinases (MAPK) are involved in a complex network which
      regulates a variety of cellular processes including proliferation, survival and
      death. The molecular characterization of the pathway has shown aberrant
      activation in several human tumors, due to the deregulation of receptor tyrosine
      kinases or to mutations of pathway components. Progress in understanding the MAPK
      network has led to the development of target-specific agents in clinical trials.
      The relevance of MAPK in response and resistance to antitumor agents has been
      recognized, although the outcome of MAPK activation can vary depending on the
      molecular background of tumor cells and on the type of activated kinase. The
      canonical cascade of MAPK, i.e., depending on the Extracellular Signal-Regulated
      Kinases (ERK), can act in protective signalling pathways, thereby limiting DNA
      damage. Since tumor cell survival can be sustained by ERK and cross talk of ERK
      with other pathways, modulation of sensitivity to antitumor agents by targeting
      the ERK cascade appears to be an amenable approach. Indeed, ERK play a role in
      resistance to both cytotoxic and target-specific agents. Preclinical studies
      support the relevance of drug combination approaches to enhance the efficacy of
      antitumor treatments. Combinations of pharmacological inhibitors of the ERK
      cascade and conventional or target-specific antitumor agents may be helpful in an
      attempt to overcome drug resistance. A deeper understanding of the genetic
      alterations of tumor cells and of tumor heterogeneity as well as of drug
      resistance mechanisms is expected to contribute to the rational design of MAPK
      mediated drug combinations that will lead to reversal of drug resistance.

PMID- 22973958
TI  - PI3K pathway inhibitors: better not left alone.
AB  - The PI3K/Akt/mTOR signaling pathway plays a key role in diverse physiologic
      processes. It is also central to many aspects of the malignant process. Genetic
      phenomena that lead to constitutive pathway activation are common in human
      cancer; the most relevant are mutations affecting the catalytic subunit of PI3K
      and loss of function of the PTEN tumor suppressor. These factors have made this
      important cascade attractive as a potential target for cancer therapeutics. A
      host of inhibitors are now in various stages of development that target key nodes
      within the PI3K pathway. To date, however, the efficacy of these agents has
      fallen short of expectation, with at least one possible explanation being the
      presence of feedback loops and cross-talk that exists within and between PI3K and
      other signaling pathways. Accordingly, enthusiasm is again high as strategies
      employing therapeutic combinations are gaining pace, with encouraging results
      documented in both preclinical studies and emerging clinical trials. Here, we
      review the agents that have reached evaluation in early phase clinical studies of
      human subjects with cancer, and discuss the rationale for and use of novel drug
      combinations.

PMID- 22973959
TI  - The intriguing interplay between therapies targeting the epidermal growth factor
      receptor, the hypoxic microenvironment and hypoxia-inducible factors.
AB  - Despite their individual key roles in promoting cancer progression and treatment
      resistance, our knowledge about the impact of tumor hypoxia on the activity of
      the epidermal growth factor receptor (EGFR) pathway in cancer and vice versa
      remains limited. Preclinical and clinical studies support an important link
      between hypoxia and upregulation of EGFR in cancers that do not display genetic
      alterations of the receptor. Subsequent EGFR signaling stimulates hypoxia
      inducible factor (HIF) signaling and thus augments induction of proteins that
      promote cellular survival in a hostile microenvironment. Considering the effects
      of EGFR-targeting agents under reduced oxygen conditions, it is now accepted
      that, together with their demonstrated antiproliferative and proapoptotic
      effects, the antiangiogenic activity of these drugs also contributes to their
      overall antitumor activity in vivo. Treatment of human tumor cells with EGFR
      inhibitors leads to decreased HIF-1alpha and VEGF secretion by tumor cells,
      resulting in vascular normalization, improved blood flow and thus improved
      oxygenation. These findings may have major implications with respect to the
      efficacy of both radiotherapy and subsequent chemotherapy when combined with EGFR
      inhibitors. A major challenge remains to assess which sequence of these drugs
      with radiation or chemotherapy is optimal. Moreover, recent data suggest that the
      lack of clinical responses to EGFR-directed therapy may be circumvented by
      supplementation of the anti-EGFR therapy with additional approaches targeting HIF
      1alpha or VEGF. Further studies thus are warranted to define the precise
      mechanistic and therapeutic implications of the hypoxic response relative to the
      EGFR signaling pathway in cancer.

PMID- 22973960
TI  - Synergistic antiproliferative and antiangiogenic effects of EGFR and mTOR
      inhibitors.
AB  - Single-agent therapy with molecularly targeted agents has shown limited success
      in tumor growth control, mainly because escape or resistance mechanisms are
      activated once a signalling molecule is inhibited. Rational combinations of
      target-specific agents could counteract this response providing a useful strategy
      in cancer treatment. In this regard, the EGFR and mTOR inhibitors have been used
      together to generate a synergistic effect and maximize the efficacy of each
      individual agent. Overall, the in vivo and in vitro evidences support the
      utilization of combinations targeting EGFR and mTOR, for malignancies
      characterized by deregulated EGFR/PI3K/Akt/ mTOR signalling cascade; whereas the
      clinical experience points out that the assessment of the therapeutic value of
      such combination awaits further investigations.

PMID- 22973961
TI  - Molecular mechanisms and modulation of key pathways underlying the synergistic
      interaction of sorafenib with erlotinib in non-small-cell-lung cancer (NSCLC)
      cells.
AB  - Combination of drugs with different targets is a logical approach to overcome
      multilevel cross-stimulation among key pathways in NSCLC progression such as
      EGFR, K-Ras and VEGFR. The sorafenib-erlotinib combination showed clinical
      activity and acceptable safety. Therefore, we evaluated mechanisms underlying
      sorafenib-erlotinib interaction in seven NSCLC cell lines selected for their
      heterogeneous pattern of EGFR and Raf-kinase-inhibitor protein (RKIP) expression,
      and EGFR/K-Ras mutations. Pharmacologic interaction was studied using MTT/SRB
      assays and the combination index (CI) method, while effects on EGFR, Erk1/2 and
      Akt phosphorylation, cell cycle and apoptosis were studied with western-blot,
      ELISA, and flow cytometry. Intracellular drug concentrations were measured with
      LC-MS/MS, whereas kinase activity profiles were generated on tyrosine kinase
      peptide substrate arrays. Synergism was detected in all cell lines, with CIs <
      0.6 in K-Ras mutated A549, SW1573 and H460, as well as in H1975 (EGFR-T790M)
      cells. Sorafenib slowed cell cycle progression and induced apoptosis, which was
      significantly increased in the combination. Moreover, sorafenib reduced Akt/ERK
      phosphorylation in erlotinib-resistant cells, associated with significant RKIP up
      regulation. No direct drug interaction was detected by LC-MS/MS measurement,
      while lysates from A549 and H1975 cells exposed to erlotinib+sorafenib showed a
      significant inhibition in the phosphorylation of 16 overlapping peptides,
      including sites from RAF, VEGFR2, PDGFR, CDK2 and SRC, suggesting new markers to
      identify NSCLC patients who are likely to respond to this treatment. In
      conclusion, several mechanisms, including apoptosis-induction, modulation of
      expression/phosphorylation of RKIP and crucial kinases contribute to erlotinib
      sorafenib synergistic interaction and should be evaluated in future trials for
      the rational development of this combination in NSCLC.

PMID- 22973963
TI  - Targeting the Akt-pathway to improve radiosensitivity in glioblastoma.
AB  - Glioblastoma multiforme (GMB) is the most malignant and common type of all
      astrocytic tumors. Current standard of care entails maximum surgical resection of
      the tumor, followed by radiotherapy and chemotherapy, usually by the alkylating
      agent Temozolomide (TMZ). Despite this aggressive combination therapy, the
      survival rate of GBM patients is still low. Deregulation of the
      phosphatidylinositol 3-kinase (PI3K) / Akt pathway is a frequent occurrence in
      GBM. Activation of the PI3K-Akt pathway results in disturbance of control of cell
      growth and cell survival, which contributes to a competitive growth advantage,
      metastatic competence as well as to therapy resistance. The PI3K-Akt pathway is
      therefore an attractive therapeutic target in GBM, because it serves as a
      convergence point for malignant processes and intervention might overcome
      resistance to chemotherapy and radiation. The present review shows the importance
      of Akt in GBM and its role in the DNA damage response. Furthermore, an overview
      is given of specific inhibitors of Akt which are currently being tested in
      preclinical and in early phase clinical studies.

PMID- 22973962
TI  - Enhancement of the antiproliferative activity of gemcitabine by modulation of c
      Met pathway in pancreatic cancer.
AB  - Pancreatic-ductal-adenocarcinoma (PDAC) is amongst the most lethal malignancies,
      mainly because of its metastatic spread and multifactorial chemoresistance. Since
      c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in
      metastasis and chemoresistance, this study evaluated the therapeutic potential of
      the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan
      1-gemcitabine-resistant cells (Capan-1-R). Crizotinib inhibited PDAC cell-growth
      with IC50 of 1.5 MUM in Capan-1-R, and synergistically enhanced the
      antiproliferative and proapoptotic activity of gemcitabine, as detected by
      sulforhodamine-B-assay, flow cytometry and combination-index method. Capan-1-R
      had higher expression of the CSC markers CD44+/CD133+/CD326+, but their combined
      expression was significantly reduced by crizotinib, as detected by quantitative
      RT-PCR and FACS-analysis. Similarly, Capan-1-R cells had significantly higher
      protein-expression of c-Met (~2-fold), and increased migratory activity, which
      was reduced by crizotinib (e.g., > 50% reduction of cell-migration in Capan-1-R
      after 8-hour exposure, compared to untreated-cells), in association with reduced
      vimentin expression. Capan-1-R had also significantly higher mRNA expression of
      the gemcitabine catabolism-enzyme CDA, potentially explaining the higher CDA
      activity and statistically significant lower levels of gemcitabine-nucleotides in
      Capan-1-R compared to Capan-1, as detected by Liquid-chromatography
      massspectrometry. Conversely, crizotinib significantly reduced CDA expression in
      both Capan-1 and Capan-1-R cells. In aggregate, these data show the ability of
      crizotinib to specifically target CSC-like-subpopulations, interfere with cell
      proliferation, induce apoptosis, reduce migration and synergistically interact
      with gemcitabine, supporting further studies on this novel therapeutic approach
      for PDAC.

PMID- 22973964
TI  - Irinotecan resistance is accompanied by upregulation of EGFR and Src signaling in
      human cancer models.
AB  - Irinotecan is a major drug for treatment of metastatic colorectal cancer and a
      promising agent for other applications like gastric cancer. Its clinical activity
      is currently limited by both intrinsic (natural) and acquired drug resistance. A
      better understanding of the underlying resistance mechanisms is needed to develop
      novel therapeutic strategies. Exposure of tumor cells to irinotecan or its active
      metabolite SN-38 is accompanied by EGFR activation, either by stimulation of EGFR
      autophosphorylation or by Src-mediated phosphorylation. Accordingly, combinations
      of irinotecan and EGFR inhibitors have been associated with supra-additive
      activity. We now show that acquired resistance to SN-38 is accompanied by
      increased expression of EGFR, HER2, HER3 and Src proteins in two colorectal
      cancer cell models as well as by Src activation. One SN-38 resistant model (HT
      29) showed increased sensitivity to erlotinib, an EGFR inhibitor, and afatinib, a
      dual EGFR/HER2 inhibitor, while the other SN-38 resistant model (HCT-116) showed
      increased resistance to erlotinib but unchanged or increased sensitivity to
      afatinib. Unexpectedly, both models showed increased or unaltered resistance to
      the Src inhibitor dasatinib. Therefore, tyrosine kinase upregulation is not
      necessarily accompanied by increased sensitivity to targeted agents. Taken
      together, our findings demonstrate that prolonged exposure to topoisomerase I
      inhibitors is accompanied by upregulation of different signal transduction
      pathways which can alter tumor sensitivity to molecular targeted agents. These
      results suggest that chemotherapy exposure may lead to creation of novel targets
      which could be exploited therapeutically.

PMID- 22973965
TI  - Development of new molecular agents targeting key signalling pathways activated
      by growth factors in human cancer.

PMID- 22973966
TI  - Responsivity to criminogenic need in forensic intellectual disability services.
AB  - BACKGROUND: Research has shown for some time that addressing criminogenic need is
      one of the crucial aspects of reducing reoffending in all types of offenders.
      Criminogenic need such as anger or inappropriate sexual interest is considered to
      be crucial in the commission of the offence. The aim of the present study is to
      investigate the extent to which forensic services address the needs of those
      accepted into services. METHOD: This study reviews the treatment for 197
      offenders with intellectual disability accepted into a range of services.
      Participants' case files were examined to ascertain the extent to which need was
      addressed through recognised therapies. A standard pro forma was used on which we
      had established good reliability across four research assistants. RESULTS: The
      most frequently referred problems were violence and sexual offending. Specialist
      forensic intellectual disability community services were significantly more
      likely to provide treatment specifically designed to address index behaviours
      when compared to generic community services and secure services. CONCLUSIONS:
      Various possible explanations of these findings are explored including staffing
      levels, diagnosed mental illness, expertise of staff and clarity of purpose in
      services.

PMID- 22973967
TI  - Comment on "comprehensive profiling of coal tar and crude oil to obtain mass
      spectra and retention indices for alkylated PAH shows why current methods err".

PMID- 22973968
TI  - Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body
      weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes.
AB  - BACKGROUND: We recently reported that short-term treatment with liraglutide (20.0
      +/- 6.4 days) reduced body weight and improved some scales of eating behavior in
      Japanese type 2 diabetes inpatients. However, it remained uncertain whether such
      liraglutide-induced improvement is maintained after discharge from the hospital.
      The aim of the present study was to determine the long-term effects of
      liraglutide on body weight, glycemic control, and eating behavior in Japanese
      obese type 2 diabetics. METHODS: Patients with obesity (body mass index (BMI) >25
      kg/m(2)) and type 2 diabetes were hospitalized at Osaka University Hospital
      between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were
      examined on admission, at discharge and at 1, 3, and 6 months after discharge.
      For the liraglutide group (BMI; 31.3 +/- 5.3 kg/m(2), n = 29), patients were
      introduced to liraglutide after correction of hyperglycemic by insulin or oral
      glucose-lowering drugs and maintained on liraglutide after discharge. Eating
      behavior was assessed in patients treated with liraglutide using The Guideline
      For Obesity questionnaire issued by the Japan Society for the Study of Obesity,
      at admission, discharge, 3 and 6 months after discharge. For the insulin group
      (BMI; 29.1 +/- 3.0 kg/m(2), n = 28), each patient was treated with insulin during
      hospitalization and glycemic control maintained by insulin after discharge.
      RESULTS: Liraglutide induced significant and persistent weight loss from
      admission up to 6 months after discharge, while no change in body weight after
      discharge was noted in the insulin group. Liraglutide produced significant
      improvements in all major scores of eating behavior questionnaire items and such
      effect was maintained at 6 months after discharge. Weight loss correlated
      significantly with the decrease in scores for recognition of weight and
      constitution, sense of hunger, and eating style. CONCLUSION: Liraglutide produced
      meaningful long-term weight loss and significantly improved eating behavior in
      obese Japanese patients with type 2 diabetes.

PMID- 22973969
TI  - Renal oxygenation during robot-assisted laparoscopic partial nephrectomy:
      characterization using laparoscopic digital light processing hyperspectral
      imaging.
AB  - Abstract Background and Purpose: Digital light processing-based hyperspectral
      imaging (DLP((r))-HSI) was adapted for use during laparoscopic surgery by
      coupling the spectral illumination source with a conventional laparoscopic light
      guide and incorporating a customized digital charge-coupled device camera for
      image acquisition. The system was used to characterize renal oxygenation during
      robot-assisted laparoscopic partial nephrectomy (RALPN) in humans. PATIENTS AND
      METHODS: After Institutional Review Board approval, laparoscopic DLP-HSI was
      performed in consecutive patients undergoing RALPN at our institution. Time
      trends in relative tissue oxygen saturation (%HbO2) were descriptively analyzed.
      Associations between %HbO2 and patient age, comorbidities, and estimated
      glomerular filtration rate (eGFR) were investigated using the Kendall tau test.
      RESULTS: Laparoscopic DLP-HSI was performed in 18 patients between May 2011 and
      February 2012. Median (interquartile range; IQR) age was 55.9 (49-67.5) years. Of
      the patients, 10/18 (56%) were men and 12/18 (66.7%) had a history of
      hypertension, diabetes, and/or tobacco use. Median (IQR) %HbO2 before, during,
      and after ischemia was 60.8% (57.9-68.2%), 53.6% (46.8-55.1%), and 61.5% (54.9
      67.6%), respectively. Baseline %HbO2 was inversely associated with preoperative
      eGFR (tau=-0.38; P=0.036), and eGFR at most recent follow-up (tau=-0.38;
      P=0.036). Baseline or ischemic %HbO2 did not correlate with hypertension,
      diabetes, and/or tobacco history. Younger patients (<56 years) had a lower median
      baseline %HbO2 (P=0.07) and a higher median preoperative eGFR (P=0.038), than
      their older counterparts. CONCLUSION: The laparoscopic HSI system successfully
      characterized dynamic changes in renal oxygenation during RALPN. Intraoperative
      laparoscopic HSI outcomes have the potential to predict postoperative individual
      kidney function.

PMID- 22973971
TI  - B-(3,3-difluoroallyl)diisopinocampheylborane for the enantioselective
      fluoroallylboration of aldehydes.
AB  - The fluoroallylboration of aldehydes with B-(3,3
      difluoroallyl)diisopinocampheylborane, which was prepared via the hydroboration
      of 1,1-difluoroallene, provides chiral 2,2-gem-difluorinated homoallylic alcohols
      in good yields and 91-97% ee.

PMID- 22973970
TI  - Nurse delivered lifestyle interventions in primary health care to treat chronic
      disease risk factors associated with obesity: a systematic review.
AB  - Nurses in primary health care (PHC) provide an increasing proportion of chronic
      disease management and preventive lifestyle advice. The databases MEDLINE,
      CINAHL, EMBASE and PsychINFO were searched and the articles were systematically
      reviewed for articles describing controlled adult lifestyle intervention studies
      delivered by a PHC nurse, in a PHC setting. Thirty-one articles describing 28
      studies were analysed by comparison group which revealed: (i) no difference of
      effect when the same intervention was delivered by a PHC nurse compared to other
      health professionals in PHC (n = 2); (ii) the provision of counselling delivered
      by a PHC nurse was more effective than health screening (n = 10); (iii)
      counselling based on behaviour change theory was more effective than the same
      dose of non-behavioural counselling when at least three counselling sessions were
      delivered (n = 3). The evidence supports the effectiveness of lifestyle
      interventions delivered by nurses in PHC to affect positive changes on outcomes
      associated with the prevention of chronic disease including: weight, blood
      pressure, cholesterol, dietary and physical activity behaviours, patient
      satisfaction, readiness for change and quality of life. The strength of
      recommendations is limited by the small number of studies within each comparison
      group and the high risk of bias of the majority of studies.

PMID- 22973972
TI  - A missense founder mutation in VLDLR is associated with Dysequilibrium Syndrome
      without quadrupedal locomotion.
AB  - BACKGROUND: Dysequilibrium syndrome is a genetically heterogeneous condition that
      combines autosomal recessive, nonprogressive cerebellar ataxia with mental
      retardation. The condition has been classified into cerebellar ataxia, mental
      retardation and disequilibrium syndrome types 1 (CAMRQ1), 2 (CAMRQ2) and 3
      (CAMRQ3) and attributed to mutations in VLDLR, CA8 and WDR81 genes, respectively.
      Quadrupedal locomotion in this syndrome has been reported in association with
      mutations in all three genes. METHODS: SNP mapping and candidate gene sequencing
      in one consanguineous Omani family from the United Arab Emirates with cerebellar
      hypoplasia, moderate mental retardation, delayed ambulation and truncal ataxia
      was used to identify the mutation. In a second unrelated consanguineous Omani
      family, massively parallel exonic sequencing was used. RESULTS: We identified a
      homozygous missense mutation (c.2117 G > T, p.C706F) in the VLDLR gene in both
      families on a shared affected haplotype block.This is the first reported
      homozygous missense mutation in VLDLR and it occurs in a highly conserved residue
      and predicted to be damaging to protein function. CONCLUSIONS: We have delineated
      the phenotype associated with dysequilibrium syndrome in two Omani families and
      identified the first homozygous missense pathogenic mutation in VLDLR gene with
      likely founder effect in the southeastern part of the Arabian Peninsula.

PMID- 22973973
TI  - Effect of chloride on nitrite-induced methaemoglobinemia in Atlantic sturgeon,
      Acipenser oxyrinchus oxyrinchus (Mitchill).
AB  - We evaluated the effects of chloride concentration on the clinical pathology in
      juvenile Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill), following
      semi-static exposures to 1 mg L(-1) nitrite for 96 h. In spring water naturally
      low in chloride (5 mg L(-1)), plasma nitrite concentrated to more than 40*
      environmental levels resulting in a severe methaemoglobinemia characterized by
      torpid behaviour, 30-fold increase in methaemoglobin fraction, anaemia,
      leucopenia and hyperkalaemia. Loss of intracellular water and potassium to
      extracellular space may have resulted in hyperkalaemia and haemodilution. Fish
      survived nitrite exposure, but 60% of torpid fish died following capture and
      tissue sampling. Fish acclimated to 10-fold higher chloride content (55 mg L(-1))
      did not concentrate nitrite in the plasma above environmental levels or develop
      methaemoglobinemia, but did exhibit similar haematology and plasma chemistry
      changes. Plasma nitrite returned to preexposure levels by 14 days following
      nitrite exposures, but severity of clinical pathology changes persisted or
      increased, suggesting that Atlantic sturgeon have reduced capacity to recover
      from methaemoglobinemia. Fish that survive methaemoglobinemia may be susceptible
      to mortality from the cumulative effects of intoxication, handling and other
      stresses for two or more weeks following nitrite remediation. Chloride buffering
      in aquaculture systems reduces the toxic effects of nitrite accumulation.

PMID- 22973974
TI  - Endoscopic management of impacted esophageal foreign bodies.
AB  - There are many reports on the endoscopic management of ingested foreign bodies in
      the upper gastrointestinal tract, however, little is known about the management
      of a specific subset of esophageal foreign bodies - impacted esophageal foreign
      bodies (IEFBs), especially perforating esophageal foreign bodies (PEFBs). The aim
      of this retrospective study on 78 cases was to report experience and outcome in
      the endoscopic management of the IEFBs in Chinese patients. From January 2006 to
      July 2011, a total of 750 patients with suspected upper gastrointestinal foreign
      bodies were admitted to the endoscopy center. Among these 750 patients, 78 cases
      that met the defined criteria of IEFBs were retrospectively enrolled in the
      present study, including 12 cases (12/78, 15.4%) with PEFBs. The major types of
      IEFBs were poultry bones (35.9%) and fish bones (17.9%). Most of the IEFBs
      (80.8%) were located in the upper esophagus, as were two thirds (66.7%) of the
      PEFBs. Foreign-body retrieval forceps were the most frequently used accessory
      devices. Extraction of IEFBs failed in eight patients (10.3%) during the
      endoscopic procedure. The difficult points in endoscopic management were PEFBs,
      IEFBs with sharp points, and those with impaction for more than 24 hours. IEFBs
      should be treated as early as possible, and their endoscopic management is safe
      and effective. Endoscopic management is the first choice for PEFBs when the
      duration of impaction is less than 24 hours and there are no abscesses outside of
      the esophageal tract as determined by a computed tomography scan. 

PMID- 22973975
TI  - Antibacterial and antiinflammatory kinetics of curcumin as a potential
      antimucositis agent in cancer patients.
AB  - The antiinflammatory agent curcumin (diferuloylmethane) has a potential to
      mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its
      bactericidal activity and determined the kinetics of its antiinflammatory effect
      on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD(r)
      Kit after 4 h of exposure to curcumin (50-200 MUM) in 18 oropharyngeal species
      commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis
      or its outer membrane vesicles were used to determine the inhibitory effect of
      curcumin on bacteria-induced proinflammatory activity as determined by cytokine
      release into the supernatant of Detroit 562 pharyngeal cells using the Luminex(r)
      xMAP(r) technology. Curcumin exerted a concentration-dependent bactericidal
      effect on all 18 species tested. After 4 h at 200 MUM, 12 species tested were
      completely killed. Preincubation of Detroit cells with 200 MUM curcumin for 5 to
      60 min resulted in complete suppression of the release of tumor necrosis factor
      alpha, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte
      macrophage-colony stimulating factor, and vascular endothelial growth factor.
      Fibroblast growth factor-2 and interferon-gamma were not affected. Repetitive
      exposure to curcumin resulted in repetitive suppression of cytokine/chemokine
      expression lasting from 4 to 6 h. Through reduction of oral microbial density as
      well as suppression of inflammation cascades curcumin may prevent cancer therapy
      induced oral mucositis, e.g., when applied as multiple daily mouth washes.

PMID- 22973976
TI  - Retroperitoneal hematoma with bone resorption around the acetabular component
      after total hip arthroplasty: a case report and review of the literature.
AB  - INTRODUCTION: Vascular complications related to cup-fixating screws penetrating
      the medial acetabular wall during total hip arthroplasty are not uncommon but
      rarely are associated with serious adverse events in the late post-operative
      period. CASE PRESENTATION: We present the case of a 77-year-old Japanese woman
      who developed progressive extensive bone resorption and large hematoma in the
      acetabulum 13 years after total hip arthroplasty. On admission to our hospital,
      she was on oral warfarin (1.5mg/day) for atrial fibrillation. About 5 months
      after the initiation of anticoagulant therapy, she suffered a major fall followed
      by massive subcutaneous and pelvic girdle bleeding, predominantly on the medial
      side of the right thigh, but a fracture or damage of total hip arthroplasty was
      not evident on an emergency orthopedic evaluation. One year after the accident, a
      routine follow-up examination showed an asymptomatic osteolytic lesion in the
      acetabulum on the right pelvis, and 2 years later our patient noticed progressive
      pain in her right hip during walking. A large osteolytic lesion was noted in the
      right acetabulum on a plain radiograph. On high-resolution computed tomography
      and magnetic resonance imaging, a huge granulomatous lesion in the acetabulum was
      suggestive of chronic hematoma in intrapelvic and extrapelvic gluteal regions. A
      closer computed tomography examination showed that one of the screws used for
      fixation of the acetabular component in the total hip arthroplasty had penetrated
      the acetabular bone and had reached the pelvic cavity. Surgery was performed in a
      single session by means of two approaches: anterior midline transperitoneal
      address to resect the low-density mass lesion followed by posterolateral
      acetabular implant re-settlement. CONCLUSIONS: Though rare, total hip
      arthroplasty-related late vascular complications could be serious and potentially
      affect the limb and quality of life.

PMID- 22973977
TI  - Development of the excretory system in a polyplacophoran mollusc: stages in
      metanephridial system development.
AB  - BACKGROUND: Two types of excretory systems, protonephridia and metanephridial
      systems are common among bilaterians. The homology of protonephridia of
      lophotrochozoan taxa has been widely accepted. In contrast, the homology of
      metanephridial systems - including coelomic cavities as functional units - among
      taxa as well as the homology between the two excretory systems is a matter of
      ongoing discussion. This particularly concerns the molluscan kidneys, which are
      mostly regarded as being derived convergently to the metanephridia of e.g.
      annelids because of different ontogenetic origin. A reinvestigation of
      nephrogenesis in polyplacophorans, which carry many primitive traits within
      molluscs, could shed light on these questions. RESULTS: The metanephridial system
      of Lepidochitona corrugata develops rapidly in the early juvenile phase. It is
      formed from a coelomic anlage that soon achieves endothelial organization. The
      pericardium and heart are formed from the central portion of the anlage. The
      nephridial components are formed by outgrowth from lateral differentiations of
      the anlage. Simultaneously with formation of the heart, podocytes appear in the
      atrial wall of the pericardium. In addition, renopericardial ducts, kidneys and
      efferent nephroducts, all showing downstream ciliation towards the internal
      lumen, become differentiated (specimen length: 0.62 mm). Further development
      consists of elongation of the kidney and reinforcement of filtration and
      reabsorptive structures. CONCLUSIONS: During development and in fully formed
      condition the metanephridial system of Lepidochitona corrugata shares many
      detailed traits (cellular and overall organization) with the protonephridia of
      the same species. Accordingly, we suggest a serial homology of various cell types
      and between the two excretory systems and the organs as a whole. The formation of
      the metanephridial system varies significantly within Mollusca, thus the mode of
      formation cannot be used as a homology criterion. Because of similarities in
      overall organization, we conclude that the molluscan metanephridial system is
      homologous with that of the annelids not only at the cellular but also at the
      organ level.

PMID- 22973978
TI  - Wavelength, concentration, and distance dependence of nonradiative energy
      transfer to a plane of gold nanoparticles.
AB  - Nonradiative energy transfer to metal nanoparticles is a technique used for
      optical-based distance measurements which is often implemented in sensing. Both
      Forster resonant energy transfer (FRET) and nanometal surface energy transfer
      (NSET) mechanisms have been proposed for emission quenching in proximity to metal
      nanoparticles. Here quenching of emission of colloidal quantum dots in proximity
      to a monolayer of gold nanoparticles is investigated. Five differently sized CdTe
      quantum dots are used to probe the wavelength dependence of the quenching
      mechanism as their emission peak moves from on resonance to off resonance with
      respect to the localized surface plasmon peak of the gold nanoparticle layer. The
      gold nanoparticle concentration and distance dependences of energy transfer are
      discussed. Photoluminescence quenching and lifetime data are analyzed using both
      FRET and NSET models and the extracted characteristic distances are compared with
      theory. Good agreement with FRET theory has been found for quantum dots with
      emission close to the localized surface plasmon resonance, though larger than
      expected Forster radii are observed for quantum dots with emission red-shifted
      with respect to the localized surface plasmon peak. Closer agreement between
      experimental and theoretical characteristic distances can be found across the
      full wavelength range within a NSET approach.

PMID- 22973979
TI  - Association between single-nucleotide polymorphisms of BRAF and papillary thyroid
      carcinoma in a Chinese population.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) is a common malignancy that frequently
      harbors a high prevalence of somatic mutations in the oncogenic BRAF gene. As a
      novel prognostic molecular marker, this gene has drawn much attention in recent
      years for its potential utility in the risk prognosis and management of PTC.
      However, the contribution of the germline variants in this gene to PTC remains
      unclear. The study herein was aimed to investigate the potential association
      between the inherited BRAF variants and PTC based on a case-control study.
      METHODS: We selected four single-nucleotide polymorphisms (SNPs) and took a
      systematic step to interrogate whether these SNPs of BRAF are associated with PTC
      risk by genotyping these SNPs from 368 patients with PTC and 564 healthy
      controls. RESULTS: In comparison of cases and controls for the four SNPs, no
      differences were observed in the genotypic and allelic frequencies, nor was there
      evidence of an association between BRAF SNPs and overall risk of PTC. After
      stratification, however, we found a significantly increased risk of PTC
      attributed to the SNP variants rs17161747, rs1042179, and rs3748093 for those
      with a family history of cancer, for smokers, and for both those of age <45 years
      and nondrinkers, respectively. Further, in the PTC cases, those carrying the
      rs3748093 variant seemed to be less susceptible to developing lymph node
      metastases, but more likely to suffer from PTC at an earlier age (<45 years).
      CONCLUSIONS: These preliminary results may provide evidence for the involvement
      of the common genetic variants scattered throughout the BRAF oncogene in the
      prediction of PTC onset and progression. In the future, enlarging the number of
      samples and performing functional studies in this gene may help to validate
      whether the association truly exists.

PMID- 22973980
TI  - Spontaneous macular hole closure without posterior vitreous detachment in a
      patient previously treated for diabetic maculopathy.

PMID- 22973981
TI  - Isolation and antioxidant activity of zeylaniin A, a new macrocyclic ellagitannin
      from Syzygium zeylanicum leaves.
AB  - Methanol extract obtained from Syzygium zeylanicum leaves exhibited potent
      antioxidant activity. The water extract obtained from this methanol extract by
      sequential extraction with hexane, chloroform, ethylacetate, and n-butanol also
      showed the strongest antioxidant activity among extracts. This water extract was
      further fractionated by column chromatography with various concentrations of
      methanol solutions. Among the 6 resultant fractions, the fraction developed with
      20% methanol exhibited the most potent antioxidant activity. The one peak among
      the three major HPLC peaks in this fraction was isolated and purified using a
      preparative HPLC. The structure of a pure compound was elucidated as a novel
      macrocyclic ellagitannin using a (1)H/(13)C NMR and a high-resolution
      electrospray ionization mass spectrometer. This newly isolated compound, which
      was named zeylaniin A, exhibited potent antioxidant activities in the assays of
      DPPH, oxygen radical absorbance capacity, and malonadehyde/gas chromatography. S.
      zeylanicum leaves can be a possible source of natural antioxidants.

PMID- 22973982
TI  - Comparative FTIR study of a new fungal rhodopsin.
AB  - Bacteriorhodopsin (BR) is a light-driven proton pump of halophilic Archaea , and
      BR-like proton-pumping rhodopsins have been discovered in Bacteria and Eucarya as
      well. Leptosphaeria rhodopsin (LR) and Phaeosphaeria Rhodopsin 2 (PhaeoRD2) are
      both fungal rhodopsins in such a functional class, even though they belong to
      different branches of the phylogenetic tree. In this study, we compared light
      induced structural changes in the K, L, and M photointermediates for PhaeoRD2,
      LR, and BR using low-temperature Fourier transform infrared (FTIR) spectroscopy.
      We observed a strongly hydrogen-bonded water molecule in PhaeoRD2 (water O-D
      stretch in D(2)O at 2258 cm(-1)) as well as in LR and BR. This observation
      provided additional experimental evidence to the concept that strongly hydrogen
      bonded water molecule is the functional determinant of light-driven proton
      pumping. The difference FTIR spectra for all the K, L, and M states are
      surprisingly similar between PhaeoRD2 and LR, but not for BR. PhaeoRD2 is more
      homologous to LR than to BR, but the difference is small. The amino acid
      identities between PhaeoRD2 and LR, and between PhaeoRD2 and BR are 34.5% and
      30.2%, respectively. In addition, the amino acids uniquely identical for the
      fungal rhodopsins are located rather far from the retinal chromophore. In fact,
      the amino acid identities within 4 A from retinal are the same among PhaeoRD2,
      LR, and BR. For more than 100 amino acids located within 12 A from retinal, the
      identities are 48.7% between PhaeoRD2 and LR, 46.0% between PhaeoRD2 and BR, and
      47.8% between LR and BR. These results suggest that protein core structures are
      equally different among the three rhodopsins. Thus, the identical FTIR spectra
      between PhaeoRD2 and LR (but not BR), even for the K state, indicate that fungal
      rhodopsins possess some common structural motif and dynamics not obvious from the
      amino acid sequences.

PMID- 22973983
TI  - Age of acquisition affects the retrieval of grammatical category information.
AB  - This study investigated age of acquisition (AoA) effects on processing
      grammatical category information of Chinese single-character words. In Experiment
      1, nouns and verbs that were acquired at different ages were used as materials in
      a grammatical category decision task. Results showed that the grammatical
      category information of earlier acquired nouns and verbs was easier to retrieve.
      In Experiment 2, AoA and predictability from orthography to grammatical category
      were manipulated in a grammatical category decision task. Results showed larger
      AoA effects under lower predictability conditions. In Experiment 3, a semantic
      category decision task was used with the same materials as those in Experiment 2.
      Different results were found from Experiment 2, suggesting that the grammatical
      category decision task is not merely the same as the semantic category decision
      task, but rather involves additional processing of grammatical category
      information. Therefore the conclusions of Experiments 1 and 2 were strengthened.
      In summary, it was found for the first time that AoA affects the retrieval of
      grammatical category information, thus providing new evidence in support of the
      arbitrary mapping hypothesis.

PMID- 22973984
TI  - ADAM23 knockdown promotes neuronal differentiation of P19 embryonal carcinoma
      cells by up-regulating P27KIP1 expression.
AB  - ADAM23 (a disintegrin and metalloprotease 23), a member of brain MDC (macrophage
      derived chemokine) family, is important for the development of CNS (central
      nervous system). P19 mouse embryonal carcinoma cells can differentiate into
      neurons when cultured in aggregates and induced with RA (retinoic acid). We have
      found that under conditions without RA induction, knocking down ADAM23 with RNAi
      (RNA interference) promoted neuronal differentiation, and similarly recombinant
      GST (glutathione transferase)-ADAM23-DIS protein inhibited neuronal
      differentiation of P19/ADAM23KD (P19/ADAM23-knockdown) cells. In P19/ADAM23KD,
      there were more cells arrested in G1 phase than normal P19 cells, due to the up
      regulation of P57KIP2 and P27KIP1 expression. P27KIP1 was up-regulated during the
      differentiation process of both P19/ADAM23KD cells without RA induction, and P19
      cells with RA induction. Transient overexpression of P27KIP1 in P19 cells also
      promoted neuronal differentiation of P19 cells. The findings indicate that ADAM23
      suppresses neuronal differentiation through its disintegrin domain, and Adam23 KD
      up-regulates P27KIP1 in P19/ADAM23KD cells, one reason that P19/ADAM23KD cells
      can differentiate into neurons without RA induction.

PMID- 22973985
TI  - Correlates of restraint and seclusion for adults with intellectual disabilities
      in community services.
AB  - BACKGROUND: Some individuals with intellectual disabilities (IDs) exhibit
      aggressive behaviour directed towards themselves, others or the environment.
      Displaying aggressive behaviour is associated with a number of negative
      consequences such as the exposure to restrictive interventions. This study aims
      to identify personal and environmental factors related to the use of restrictive
      measures among persons with IDs living in the community. METHODS: Data for 81
      adults with IDs were collected through a mail survey. The questionnaires acquired
      information on demographic variables, physical health and psychiatric diagnoses,
      medication, residential setting, support worker experience and prevalence of
      restraint and seclusion. The type and severity of aggressive behaviours were
      measured by the Modified Overt Aggression Scale. RESULTS: The prevalence of
      restrictive measures was 63.0%: 44.4% seclusion, 42.0% physical restraint and
      27.2% mechanical restraint. The mode of communication, anxiolytic medication,
      severity of the aggressive behaviours, presence of a functional assessment on
      aggressive behaviours, and support workers' experience with persons with IDs were
      predictors of restrictive measures. CONCLUSION: The results of this study have
      several clinical implications for practitioners working with persons with IDs who
      exhibit aggressive behaviours. More research is needed to expand our
      understanding of the use of restrictive measures and reduce its frequency.

PMID- 22973986
TI  - Impact of admission glucose and diabetes on recanalization and outcome after
      intra-arterial thrombolysis for ischaemic stroke.
AB  - BACKGROUND: Stroke patients with diabetes and admission hyperglycaemia have worse
      outcomes than non-diabetics, with or without intravenous thrombolysis. Poor
      vessel recanalization was reported in diabetics treated with intravenous
      thrombolysis. AIMS: This study aimed to determine the impact of admission glucose
      and diabetes on recanalization and outcome after intra-arterial thrombolysis.
      METHODS: We analysed 389 patients (213 men, 176 women) treated with intra
      arterial thrombolysis. The association of diabetes and admission glucose value
      with recanalization, outcome, mortality, and symptomatic intracranial haemorrhage
      was determined. Recanalization was classified according to thrombolysis in
      myocardial infarction grades. Outcome was measured using the modified Rankin
      Scale at three-months and categorized as favourable (modified Rankin Scale 0-2)
      or poor (modified Rankin Scale 3-6). RESULTS: The rate of partial or complete
      recanalization (thrombolysis in myocardial infarction 2-3) did not differ between
      patients with and without diabetes (67% vs. 66%; P = 1.000). Mean admission
      glucose values were similar in patients with poor recanalization (thrombolysis in
      myocardial infarction 0-1) and patients with partial or complete recanalization
      (thrombolysis in myocardial infarction 2-3; 7.3 vs. 7.3 mmol/l; P = 0.746).
      Follow-up at three-months was obtained in 388 of 389 patients. Clinical outcome
      was favourable (modified Rankin Scale 0-2) in 189 patients (49%) and poor
      (modified Rankin Scale 3-6) in 199 patients (51%). Mortality at three-months was
      20%. Diabetics were more likely to have poor outcome (72% vs. 48%; P = 0.001) and
      to be dead (30% vs. 19%; P = 0.044) at three-months. After multivariable
      analysis, there remained an independent relationship between diabetes and outcome
      (P = 0.003; odds ratio 3.033, 95% confidence interval 1.452-6.336), but not with
      mortality (P = 0.310; odds ratio 1.436; 95% confidence interval 0.714-2.888).
      Moreover, higher age (P = 0.001; odds ratio 1.039; 95% confidence interval 1.017
      1.061), higher baseline National Institutes of Health Stroke Scale score (P <
      0.0001; odds ratio 1.130; 95% confidence interval 1.079-1.182), location of
      vessel occlusion as categorical variable (P < 0.0001), poor collaterals (P =
      0.02; odds ratio 1.587; 95% confidence interval 1.076-2.341), poor vessel
      recanalization (P < 0.0001; odds ratio 4.713; 95% confidence interval 2.627
      8.454), and higher leucocyte count (P = 0.032; odds ratio 1.094; 95% confidence
      interval 1.008-1.188) were independent baseline predictors of poor outcome.
      Higher admission glucose was associated with poor outcome (P = 0.006) and
      mortality (P < 0.0001). After multivariate analyses, glucose remained
      independently associated with poor outcome (P = 0.019; odds ratio 1.150; 95%
      confidence interval 1.023-1-292) and mortality (P = 0.005; odds ratio 1.183; 95%
      confidence interval 1052-1.331). The rate of symptomatic intracranial haemorrhage
      was similar in diabetics and non-diabetics (6.7% vs. 4.6%; P = 0.512). Mean
      admission glucose was higher in patients with symptomatic intracranial
      haemorrhage than without (8.58 vs. 7.26 mmol/l; P = 0.010). Multivariable
      analysis confirmed an independent association between admission glucose and
      symptomatic intracranial haemorrhage (P = 0.027; odds ratio 1.187; 95% confidence
      interval 1.020-1.381). CONCLUSIONS: Diabetes and glucose value on admission did
      not influence recanalization after intra-arterial thrombolysis; nevertheless,
      they were independent predictors of poor outcome after intra-arterial
      thrombolysis and a higher admission glucose value was an independent predictor of
      symptomatic intracranial haemorrhage. This indicates that factors on the
      capillary, cellular, or metabolic level may account for the worse outcome in
      patients with elevated glucose value and diabetes.

PMID- 22973987
TI  - Management of urolithiasis in live-related kidney donors.
AB  - OBJECTIVE: To analyze our experience in management of urolithiasis in renal
      donors. MATERIALS AND METHODS: The stones were treated either pretransplant or
      posttransplant. The Amsterdam forum criteria for acceptance of living donors were
      used for donor selection. The donors underwent the following procedures:
      pretransplant extracorporeal shock wave lithotripsy (ESWL) (n=5), pretransplant
      retrograde intrarenal surgery (RIRS) (n=1), ex-vivo ureteroscopy (ex-vivo URS)
      (n=1), and ex-vivo pyelolithotomy (ex-vivo Pyl) (n=2); intraoperative Double-J
      stent; and observation (n=3). Data were analyzed for technical feasibility,
      intraoperative and postoperative complications, and stone clearance. RESULTS: The
      male and female ratio was 4:8 and average age was 52.3 years (38-71). In the
      pretransplant ESWL group, average of 740 shocks (600-1500) was given; the power
      was not ramped up beyond 12 kV. Ex-vivo URS was performed on bench with 6F
      pediatric cystoscope, while in the ex-vivo Pyl, a 12F nephroscope was introduced
      via a pyelotomy and stones were retrieved intact with a dormia basket. A
      postoperative ultrasound at one month revealed complete clearance of stones in
      all except one donor. At a mean follow-up of 36 months (10-58), there was no
      stone recurrence in donor or recipient. CONCLUSIONS: This report shows the
      feasibility and safety of ex-vivo URS and ex-vivo Pyl in living donors, in select
      cases with subcentimeter calculi, an option of conservative management with
      Double-J stent is safe. ESWL/RIRS can be performed safely in the pretransplant
      setting. Proper donor selection and follow-up are crucial to success. We propose
      a treatment selection algorithm for management of these donors.

PMID- 22973988
TI  - Spontaneous clostridial myonecrosis after pregnancy - emergency treatment to the
      limb salvage and functional recovery: a case report.
AB  - Clostridial myonecrosis (CM) is a rare, life threatening necrotizing infection of
      a skeletal muscle caused by Clostridium perfringens in the majority of cases. The
      diagnosis may be difficult because of few diagnostic and cutaneous signs early in
      its course. Standard therapy involves surgical debridements of a devitalized
      tissue and high-dose organism-specific antibiotic therapy. The hyperbaric oxygen
      has also showed its usefulness in the treatment of these infections. Autograft
      systems as tissue replacement, based on bioengineered materials, have been
      demonstrated to be safe and effective treatments for chronic wounds and a
      suitable physiotherapy is recommended for the recovery of functional impairments
      of upper extremities. We present a rare case of CM of right upper limb treated
      with a combination of standard treatments and new techniques. 

PMID- 22973989
TI  - Cell dynamics in cervical loop epithelium during transition from crown to root:
      implications for Hertwig's epithelial root sheath formation.
AB  - BACKGROUND AND OBJECTIVE: Some clinical cases of hypoplastic tooth root are
      congenital. Because the formation of Hertwig's epithelial root sheath (HERS) is
      an important event for root development and growth, we have considered that
      understanding the HERS developmental mechanism contributes to elucidate the
      causal factors of the disease. To find integrant factors and phenomenon for HERS
      development and growth, we studied the proliferation and mobility of the cervical
      loop (CL). MATERIAL AND METHODS: We observed the cell movement of CL by the DiI
      labeling and organ culture system. To examine cell proliferation, we carried out
      immunostaining of CL and HERS using anti-Ki67 antibody. Cell motility in CL was
      observed by tooth germ slice organ culture using green fluorescent protein mouse.
      We also examined the expression of paxillin associated with cell movement.
      RESULTS: Imaging using DiI labeling showed that, at the apex of CL, the
      epithelium elongated in tandem with the growth of outer enamel epithelium (OEE).
      Cell proliferation assay using Ki67 immunostaining showed that OEE divided more
      actively than inner enamel epithelium (IEE) at the onset of HERS formation. Live
      imaging suggested that mobility of the OEE and cells in the apex of CL were more
      active than in IEE. The expression of paxillin was observed strongly in OEE and
      the apex of CL. CONCLUSION: The more active growth and movement of OEE cells
      contributed to HERS formation after reduction of the growth of IEE. The
      expression pattern of paxillin was involved in the active movement of OEE and
      HERS. The results will contribute to understand the HERS formation mechanism and
      elucidate the cause of anomaly root.

PMID- 22973990
TI  - Enhanced mobility of fullerene (C60) nanoparticles in the presence of stabilizing
      agents.
AB  - Experimental and mathematical modeling studies were performed to examine the
      effects of stabilizing agents on the transport and retention of fullerene
      nanoparticles (nC(60)) in water-saturated quartz sand. Three stabilizing systems
      were considered: naturally occurring compounds known to stabilize nanoparticles
      (Suwannee river humic acid (SRHA) and fulvic acid (SRFA)), synthetic additives
      used to enhance nanoparticle stability (Tween 80, a nonionic surfactant), and
      residual contaminants resulting from the manufacturing process (tetrahydrofuran
      (THF)). The results of column experiments demonstrated that the presence of THF,
      at concentrations up to 44.5 mg/L, did not alter nC(60) transport and retention
      behavior, whereas addition of SRHA (20 mg C/L), SRFA (20 mg C/L), or Tween 80
      (1000 mg/L) to the influent nC(60) suspensions dramatically increased the
      mobility of nC(60), as demonstrated by coincidental nanoparticle and nonreactive
      tracer effluent breakthrough curves (BTCs) and minimal nC(60) retention. When
      columns were preflushed with surfactant, nC(60) transport was significantly
      enhanced compared to that in the absence of a stabilizing agent. The presence of
      adsorbed Tween 80 resulted in nC(60) BTCs characterized by a declining plateau
      and retention profiles that exhibited hyperexponential decay. The observed nC(60)
      transport and retention behavior was accurately captured by a mathematical model
      that accounted for coupled surfactant adsorption-desorption dynamics, surfactant
      nanoparticle interactions, and particle attachment kinetics.

PMID- 22973991
TI  - Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of
      portal hypertension in chronic liver disease.
AB  - OBJECTIVES: Transient elastography (TE), as a non-invasive method, has been
      studied for evaluation of portal hypertension in patients with chronic liver
      diseases (CLD) with variable results. We studied the performance of TE for
      detection of significant portal hypertension, oesophageal varices and large
      oesophageal varices using meta-analysis. METHODS: PubMed, the Cochrane Library,
      EMBASE and ISI web of Knowledge were searched. The studies published in English
      relating to the diagnostic value of TE for significant portal hypertension,
      oesophageal varices and large oesophageal varices in patients with CLD were
      collected. RESULTS: A total of 18 studies, which included 3644 patients were
      analysed. Summary sensitivity and specificity were 0.90 (95% confidence interval
      (CI), 0.81-0.95) and 0.79 (95% CI, 0.58-0.91) for significant portal
      hypertension, and 0.87 (95% CI, 0.80-0.92) and 0.53 (95% CI, 0.36-0.69) for
      oesophageal varices and 0.86 (95% CI, 0.71-0.94) and 0.59 (95% CI, 0.45-0.72) for
      large oesophageal varices respectively. The HSROCs were 0.93 for significant
      portal hypertension, 0.84 for oesophageal varices and 0.78 for large oesophageal
      varices respectively. TE was very informative with 81% probability of correctly
      detection significant portal hypertension following a 'positive' measurement
      (over the threshold value) and lowering the probability of disease to as low as
      11% when 'negative' measurement (below the threshold value) when pre-test
      probability was 50% whereas, for oesophageal varices or large oesophageal
      varices, the probability of a correct diagnosis following a 'positive'
      measurement did not exceeded 70%. CONCLUSIONS: TE could be used as a good
      screening tool for significant portal hypertension, but only moderate diagnostic
      utility for the prediction of oesophageal varices or large oesophageal varices.

PMID- 22973993
TI  - Method for estimating S(N)1 rate constants: solvolytic reactivity of benzoates.
AB  - Nucleofugalities of pentafluorobenzoate (PFB) and 2,4,6-trifluorobenzoate (TFB)
      leaving groups have been derived from the solvolysis rate constants of X,Y
      substituted benzhydryl PFBs and TFBs measured in a series of aqueous solvents, by
      applying the LFER equation: log k = s(f)(E(f) + N(f)). The heterolysis rate
      constants of dianisylmethyl PFB and TFB, and those determined for 10 more
      dianisylmethyl benzoates in aqueous ethanol, constitute a set of reference
      benzoates whose experimental DeltaG(?) have been correlated with the DeltaH(?)
      (calculated by PCM quantum-chemical method) of the model epoxy ring formation.
      Because of the excellent correlation (r = 0.997), the method for calculating the
      nucleofugalities of substituted benzoate LGs have been established, ultimately
      providing a method for determination of the S(N)1 reactivity for any benzoate in
      a given solvent. Using the DeltaG(?) vs DeltaH(?) correlation, and taking s(f)
      based on similarity, the nucleofugality parameters for about 70 benzoates have
      been determined in 90%, 80%, and 70% aqueous ethanol. The calculated intrinsic
      barriers for substituted benzoate leaving groups show that substrates producing
      more stabilized LGs proceed over lower intrinsic barriers. Substituents on the
      phenyl ring affect the solvolysis rate of benzhydryl benzoates by both field and
      inductive effects.

PMID- 22973992
TI  - Bluetongue: a historical and epidemiological perspective with the emphasis on
      South Africa.
AB  - Bluetongue (BT) is a non-contagious, infectious, arthropod transmitted viral
      disease of domestic and wild ruminants that is caused by the bluetongue virus
      (BTV), the prototype member of the Orbivirus genus in the family Reoviridae.
      Bluetongue was first described in South Africa, where it has probably been
      endemic in wild ruminants since antiquity. Since its discovery BT has had a major
      impact on sheep breeders in the country and has therefore been a key focus of
      research at the Onderstepoort Veterinary Research Institute in Pretoria, South
      Africa. Several key discoveries were made at this Institute, including the
      demonstration that the aetiological agent of BT was a dsRNA virus that is
      transmitted by Culicoides midges and that multiple BTV serotypes circulate in
      nature. It is currently recognized that BT is endemic throughout most of South
      Africa and 22 of the 26 known serotypes have been detected in the region.
      Multiple serotypes circulate each vector season with the occurrence of different
      serotypes depending largely on herd-immunity. Indigenous sheep breeds, cattle and
      wild ruminants are frequently infected but rarely demonstrate clinical signs,
      whereas improved European sheep breeds are most susceptible. The immunization of
      susceptible sheep remains the most effective and practical control measure
      against BT. In order to protect sheep against multiple circulating serotypes,
      three pentavalent attenuated vaccines have been developed. Despite the proven
      efficacy of these vaccines in protecting sheep against the disease, several
      disadvantages are associated with their use in the field.

PMID- 22973994
TI  - Evaluation of effectiveness of erbium:yttrium-aluminum-garnet laser on atrophic
      facial acne scars with 22-MHz digital ultrasonography in a Turkish population.
AB  - Scar formation due to acne is a common problem among the young population and
      significantly affects their quality of life. The aim of this study was to
      evaluate the efficacy of erbium:yttrium-aluminum-garnet (Er:YAG) laser
      resurfacing for acne scars and to objectively demonstrate the altering of
      collagen density in the dermis by 22-MHz digital ultrasonography. Twenty-one
      patients, aged 19-55 years, with facial acne scars were treated with Er:YAG
      laser. The results of the laser resurfacing were evaluated for the degree of
      clinical improvement, alteration of the collagen density by 22-MHz digital
      ultrasonography and any adverse effects at 3 months. At 3 months after the
      treatment, good (in 12 patients) and near total (in four patients) clinical
      improvement was noted in most of the patients compared to baseline. Overall
      treatment results were 76% (both near total and good) in 16 patients. By
      ultrasonographic evaluation, the average density of dermal collagen (total
      density/number of patients) of 21 patients was 32.714 (right cheek) and 32.142
      (left cheek) before laser facial resurfacing. At the third month after treatment,
      the average density of dermal collagen of 21 patients was 36.380 (right cheek)
      and 38.809 (left cheek). In conclusion, Er:YAG laser skin resurfacing was found
      to be a safe and effective treatment modality for treatment of atrophic facial
      acne scars. As public demand grows for less invasive modalities to approach
      clinical diagnosis and evaluation, digital ultrasonography seems to provide an
      easy and confidential method for collagen density evaluation.

PMID- 22973995
TI  - Primary squamous cell carcinoma of the pancreas: a case report and review of the
      literature.
AB  - INTRODUCTION: Primary squamous cell carcinoma of the pancreas is a rare tumor
      with poor prognosis and is found in the literature only as case reports. The
      optimal management course remains poorly defined. We present a case of primary
      basaloid squamous cell carcinoma of the pancreas metastatic to the liver, which
      was treated with surgery and systemic chemotherapy. Our patient survived for 15
      months: the longest survival reported in the literature to date. CASE
      PRESENTATION: A 70-year-old Caucasian man presented to hospital with a three
      month history of weight loss, pruritus and icterus. Imaging studies confirmed the
      presence of an operable mass lesion in the head of the pancreas. Following a
      pancreaticoduodenectomy, histology results led us to make a diagnosis of squamous
      cell carcinoma. Postoperative restaging showed multiple metastases in the liver.
      He underwent palliative systemic chemotherapy with cisplatin and 5-fluorouracil
      achieving partial response and an excellent quality of life. He then went on to
      start second-line chemotherapy, but unfortunately died of sepsis soon thereafter.
      CONCLUSIONS: This case report emphasizes that achievement of a worthwhile
      objective and symptomatic palliative response is possible using platinum-based
      chemotherapy in squamous cell carcinoma of the pancreas.

PMID- 22973996
TI  - p14ARF repression induced by promoter methylation associated with metastasis in
      esophageal squamous cell carcinoma.
AB  - The objective of this study is to evaluate the promoter methylation status of the
      p14ARF in esophageal squamous cell carcinoma (ESCC). Cell lines were treated with
      the demethylation agent 5-aza-2'-deoxycytidine, and p14ARF messenger RNA (mRNA)
      expression was detected by reverse transcription-polymerase chain reaction. We
      analyzed the methylation status of p14ARF promoter by methylation-specific
      polymerase chain reaction in 50 ESCC and their noncarcinoma tissues. Then
      demethylation caused by 5-aza-2'-deoxycytidine increased the p14ARF mRNA
      expression level in esophagus cancer cell lines. p14ARF methylation was found in
      48% (24 of 50) of ESCC patients but only in 18% (9 of 50) corresponding
      noncarcinoma tissues (P = 0.001). There was a statistically significant
      correlation between the presence of methylation and tumor metastasis (P < 0.001).
      The p14ARF mRNA was lower in ESCC tissues than nontumor tissues (mean +/-
      standard deviation, 0.47 +/- 0.32 vs. 1.40 +/- 0.58; P = 0.002). Meanwhile, a
      signification association was found between the methylation status of p14ARF
      promoter and p14ARF mRNA expression in tissues (P < 0.05). The aberrant promoter
      methylation of p14ARF is a common phenomenon in ESCC, which may be an important
      mechanism of downregulating p14ARF mRNA expression. 

PMID- 22973997
TI  - Who reads telemedicine?

PMID- 22973999
TI  - Haematological changes in elite kayakers during a training season.
AB  - This study monitored haematological markers in response to training load in elite
      kayakers during a training season. The sample comprised eight elite kayakers aged
      22 +/- 4.2 years with a 77.2 +/- 6.7 kg body mass and a 177.5 +/- 5.6 cm stature.
      The initial [Formula: see text]O(2max) was 61.2 +/- 5.5 mL.kg(-1).min(-1). The
      control group consisted of six healthy males, aged 18.6 +/- 1.1 years, with an
      81.3 +/- 13.8 kg body mass and a 171.9 +/- 4.5 cm stature. Blood samples were
      collected at the beginning of the training season after an off-training period of
      six weeks (t(0)), at the 11th week after the application of high training volumes
      (t(1)), at the 26th week after an intense training cycle (t(2)), and at the 31st
      week at the end of a tapering phase (t(3)). Differences between time points were
      detected using ANOVA and the Bonferroni post hoc test. Significant changes were
      found after the intense training cycle (t(2)), lymphocytes decreased while
      haemoglobin, mean corpuscular volume, mean corposcular haemoglobin, mean
      concentration of corpuscular hemoglobin concentration, platelets distribution
      width, and red blood cell distribution width values increased when compared with
      baseline values. At t(3), a reduction in monocyte numbers and an increase in mean
      platelet volume compared with baseline values were seen. By reducing the volume
      and intensity of training, many variables returned to values close to those at
      baseline. Although many athletes had accumulated responses over time due to
      training, they still suffered transient changes that appear to be influenced by
      training load. Haemorheology monitoring may help detect health risks, especially
      during times of intensified training.

PMID- 22973998
TI  - Consequences of phosphoenolpyruvate:sugar phosphotranferase system and pyruvate
      kinase isozymes inactivation in central carbon metabolism flux distribution in
      Escherichia coli.
AB  - BACKGROUND: In Escherichia coli phosphoenolpyruvate (PEP) is a key central
      metabolism intermediate that participates in glucose transport, as precursor in
      several biosynthetic pathways and it is involved in allosteric regulation of
      glycolytic enzymes. In this work we generated W3110 derivative strains that lack
      the main PEP consumers PEP:sugar phosphotransferase system (PTS-) and pyruvate
      kinase isozymes PykA and PykF (PTS-pykA- and PTS-pykF-). To characterize the
      effects of these modifications on cell physiology, carbon flux distribution and
      aromatics production capacity were determined. RESULTS: When compared to
      reference strain W3110, strain VH33 (PTS-) displayed lower specific rates for
      growth, glucose consumption and acetate production as well as a higher biomass
      yield from glucose. These phenotypic effects were even more pronounced by the
      additional inactivation of PykA or PykF. Carbon flux analysis revealed that PTS
      inactivation causes a redirection of metabolic flux towards biomass formation. A
      cycle involving PEP carboxylase (Ppc) and PEP carboxykinase (Pck) was detected in
      all strains. In strains W3110, VH33 (PTS-) and VH35 (PTS-, pykF-), the net flux
      in this cycle was inversely correlated with the specific rate of glucose
      consumption and inactivation of Pck in these strains caused a reduction in growth
      rate. In the PTS- background, inactivation of PykA caused a reduction in Ppc and
      Pck cycling as well as a reduction in flux to TCA, whereas inactivation of PykF
      caused an increase in anaplerotic flux from PEP to OAA and an increased flux to
      TCA. The wild-type and mutant strains were modified to overproduce L
      phenylalanine. In resting cells experiments, compared to reference strain, a 10,
      4 and 7-fold higher aromatics yields from glucose were observed as consequence of
      PTS, PTS PykA and PTS PykF inactivation. CONCLUSIONS: Metabolic flux analysis
      performed on strains lacking the main activities generating pyruvate from PEP
      revealed the high degree of flexibility to perturbations of the central metabolic
      network in E. coli. The observed responses to reduced glucose uptake and PEP to
      pyruvate rate of conversion caused by PTS, PykA and PykF inactivation included
      flux rerouting in several central metabolism nodes towards anabolic biosynthetic
      reactions, thus compensating for carbon limitation in these mutant strains. The
      detected cycle involving Ppc and Pck was found to be required for maintaining the
      specific growth and glucose consumption rates in all studied strains. Strains
      VH33 (PTS-), VH34 (PTS-pykA-) and VH35 (PTS-pykF-) have useful properties for
      biotechnological processes, such as increased PEP availability and high biomass
      yields from glucose, making them useful for the production of aromatic compounds
      or recombinant proteins.

PMID- 22974000
TI  - Aquaporins 6-12 in the human eye.
AB  - PURPOSE: Aquaporins (AQPs) are widely expressed and have diverse distribution
      patterns in the eye. AQPs 0-5 have been localized at the cellular level in human
      eyes. We investigated the presence of the more recently discovered AQPs 6-12 in
      the human eye. METHODS: RT-PCR was performed on fresh tissue from two human eyes
      divided into the cornea, corneal limbus, ciliary body and iris, lens, choroid,
      optic nerve, retina and sclera. Each structure was examined to detect the mRNA of
      AQPs 6-12. Twenty-one human eyes were examined using immunohistochemical and
      immunofluorescence techniques to determine the topographical localization of AQPs
      6-12. RESULTS: mRNA transcripts of AQP7, AQP9 and AQP11 were found in the ciliary
      body, corneo-limbal tissue, optic nerve, retina and sclera. AQP9 and AQP11 mRNA
      was also detected in the choroid. No mRNA of AQP6, AQP8, AQP10 or AQP12 was
      detected. Anti-AQP7 immunolabelling was detected in the corneal epithelium,
      corneal endothelium, trabecular meshwork endothelium, ciliary epithelia, lens
      epithelium, the inner and outer limiting membrane of the retina, the retinal
      pigment epithelium and the capillary endothelium of all parts of the eye. AQP9
      immunolabelling was detected in the nonpigmented ciliary epithelium and retinal
      ganglion cells. AQP11 immunolabelling was detected in the corneo-limbal
      epithelium, nonpigmented ciliary epithelium and inner limiting membrane of the
      retina. CONCLUSION: Selective expression of AQP7, AQP9 and AQP11 was found within
      various structures of the human eye. The detection of these aquaporins in the eye
      implies a role that may be related not only to water transport but also to the
      transport of glycerol, lactate and ammonia, with importance for metabolism,
      especially in the retina.

PMID- 22974001
TI  - Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line
      (WiDr): in vitro and in vivo studies.
AB  - Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized
      form (dehydroascorbic acid; DHA), may act in physiological conditions as an
      antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic
      effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell
      line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow
      cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show
      that the reduced form of vitamin C induces an anti-proliferative and cytotoxic
      effect in adenocarcinoma colorectal cells under study. The results obtained in
      vivo after treatment with AA showed a large reduction in the rate of tumor
      growth. Such understanding can guide decisions about which colorectal cancer
      patients might potentially benefit from vitamin C pharmacologic therapy.

PMID- 22974003
TI  - Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid.
AB  - Reactive oxygen species (ROS) have been implicated in a variety of inflammatory
      diseases including cardiovascular disease (CVD), cancer, diabetes, Alzheimer's
      disease, autism, cataracts and aging. When endogenous mechanisms for the
      maintenance of redox homeostasis are overwhelmed, dietary intake of antioxidants
      contributes substantially to balancing the body's oxidant/antioxidant status.
      Ginsenosides are thought to be primarily responsible for the pharmacological
      effect of P. ginseng root extracts on oxidative stress and inflammation. However,
      little is known about the underlying antioxidant mechanisms of individual
      ginsenoside; specifically, the reactivity of ginsenoside Rb1 with ROS has not
      been well studied. We found that Rb1 can significantly and selectively reduce
      hydroxyl radical (?OH) and hypochlorous acid (HOCl), two of the strongest ROS,
      with unique molecular mechanisms in a cell-free system. Rb1 directly scavenges
      the ?OH and protects plasmid DNA from damage induced by ?OH. ?OH likely attacks
      the double bond on the side chain of Rb1 as well as hydrogen atoms adjacent to
      the -OH groups, including those of sugar moieties. Rb1 also shows a high
      reactivity to HOCl and effectively inhibits HOCl-induced tyrosine chlorination in
      a cell free system. HOCl is added to the double bond of Rb1; the -Cl group and 
      OH group of HOCl possibly bond at C-24 and C-25 of Rb1 based on the
      regioselectivity of Markovnikov's Rule. To our knowledge, this is the first
      demonstration that ginsenoside Rb1 scavenges HOCl and protects tyrosine from HOCl
      induced chlorination. Thus, this study reveals unique antioxidant mechanisms of
      individual ginsenoside Rb1, which may contribute to the pharmacological effect of
      P. ginseng and to the development of effective strategies for clinical
      applications of ginsenosides.

PMID- 22974002
TI  - Quantitative muscle strength assessment in duchenne muscular dystrophy:
      longitudinal study and correlation with functional measures.
AB  - BACKGROUND: The aim of this study was to perform a longitudinal assessment using
      Quantitative Muscle Testing (QMT) in a cohort of ambulant boys affected by
      Duchenne muscular dystrophy (DMD) and to correlate the results of QMT with
      functional measures. This study is to date the most thorough long-term evaluation
      of QMT in a cohort of DMD patients correlated with other measures, such as the
      North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT). METHODS:
      This is a single centre, prospective, non-randomised, study assessing QMT using
      the Kin Com((r)) 125 machine in a study cohort of 28 ambulant DMD boys, aged 5 to
      12 years. This cohort was assessed longitudinally over a 12 months period of time
      with 3 monthly assessments for QMT and with assessment of functional abilities,
      using the NSAA and the 6MWT at baseline and at 12 months only. QMT was also used
      in a control group of 13 healthy age-matched boys examined at baseline and at 12
      months. RESULTS: There was an increase in QMT over 12 months in boys below the
      age of 7.5 years while in boys above the age of 7.5 years, QMT showed a
      significant decrease. All the average one-year changes were significantly
      different than those experienced by healthy controls. We also found a good
      correlation between quantitative tests and the other measures that was more
      obvious in the stronger children. CONCLUSION: Our longitudinal data using QMT in
      a cohort of DMD patients suggest that this could be used as an additional tool to
      monitor changes, providing additional information on segmental strength.

PMID- 22974004
TI  - The effect of cyclosporine initiation time on the outcome of matched allogeneic
      stem-cell transplantation following fludarabine-based conditioning.
AB  - Cyclosporine (CSA) is the most commonly used medication for GVHD prophylaxis. The
      initiation time varies from day -4 to day 0. Initially, we gave CSA starting on
      day -1. However, since 2003 we have changed CSA initiation timing policy in most
      of our protocols to day -4, to achieve stable and controlled pretransplant CSA
      levels. Here, we assessed if initiation time impact the outcome of allogeneic
      stem-cell transplantation (allo-SCT). Data of 261 patients who underwent allo-SCT
      for hematological malignancies from a fully matched donor, treated with CSA as a
      single agent for GVHD prophylaxis were prospectively collected. Patients were
      divided according to CSA initiation time and analyzed for outcome. The acute GVHD
      severity, cGVHD extent, GVHD-associated mortality were significantly lower in the
      CSA -4 group. There was no difference in the rate and timing of acute or chronic
      GVHD. Overall survival did not differ between the groups. We conclude that the
      initiation of CSA at day -4 reduced the severity of aGVHD, extent of cGVHD, and
      GVHD-associated mortality without impact on overall survival.

PMID- 22974005
TI  - Ablation of small renal masses: practice patterns at academic institutions in the
      United States.
AB  - PURPOSE: We aimed to determine the current practice patterns at academic
      institutions in the use of ablative technologies for the management of small
      renal masses. PATIENTS AND METHODS: Mail surveys were sent to 124 academic
      institutions in the United States. The survey consisted of 12 questions
      pertaining to institutional demographic information, the use of ablation
      technology for small renal masses, the role of the urologist in ablation, and
      biopsy preferences prior to treatment. RESULTS: The overall response rate was 52%
      (64/124). Ablation was offered by all of the academic centers that responded to
      the survey and included 73% percutaneous cryoablation, 52% percutaneous
      radiofrequency ablation, 83% laparoscopic cryoablation, and 20% laparoscopic
      radiofrequency ablation. Eighty-eight percent of institutions performed one to
      five total ablation procedures each month. Urologists alone performed 13% of
      ablation procedures, radiologists performed 45% of ablation procedures, and a
      combined approach (urologist and radiologist present) was used in 43% of the
      institutions. When questioned about their role during percutaneous ablation, we
      found that urologists were present at the time of ablation in 59% of
      institutions, in 32% of institutions urologists placed the needles for ablation,
      and in 98% of institutions urologists were responsible for the postoperative care
      of the patient. Eighty-nine percent of academic institutions performed a biopsy
      of the renal mass with 67% performing a core biopsy, 5% performing a fine-needle
      aspiration (FNA), and 28% performing both a core biopsy and FNA. Nineteen percent
      of institutions performed a renal mass biopsy prior to the day of the procedure
      so that the pathology was known prior to ablation. CONCLUSIONS: Ablative
      technologies are well utilized for the treatment of small renal masses at current
      academic institutions with urologists directly involved in the ablation procedure
      in only half of the institutions. While preablation biopsy is common, pathology
      is rarely known prior to ablation.

PMID- 22974006
TI  - Bartlett's schema theory: the unreplicated "portrait d'homme" series from 1932.
AB  - In 1932, Frederic Bartlett laid the foundation for the later schema theory. His
      key assumption of previous knowledge affecting the processing of new stimuli was
      illustrated in the famous "portrait d'homme" series. Sequenced reproductions of
      ambiguous stimuli showed progressive object-likeness. As Bartlett pointed out,
      activation of specific schemata, for instance "the face schema", biases memory
      retrieval towards such schemata. In five experiments (Experiment 1, n = 53;
      Experiment 2, n = 177; Experiment 3, n = 36; Experiment 4, n = 6; Experiment 5, n
      = 2), we tested several factors potentially influencing retrieval biases-for
      example, by varying the general procedure of reproduction (repeated vs. serial)
      and by omitting versus providing visual or semantic cues for activating face
      schemata. Participants inspected face-like stimuli with the caption "portrait of
      the human" and reproduced them repeatedly under specific conditions. None of the
      experiments revealed a systematic tendency towards Bartlett's described case,
      even when the participants were explicitly instructed to draw "a face" like the
      previously inspected one. In one of the "serial reproduction" experiments, we
      even obtained contrary effects with decreasing face-likeness over the
      reproduction generations. A close analysis of the original findings raises
      questions about the replicability of Bartlett's findings, qualifying the
      "portrait d'homme" series more or less as an illustrative example of the main
      idea of reconstructive memory.

PMID- 22974007
TI  - Response to the letter to the editor by Armistead-jehle and Lee on Harch et Al.,
      "A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post
      concussion syndrome and post-traumatic stress disorder".

PMID- 22974008
TI  - Osteopontin alters the functional profile of porcine microglia in vitro.
AB  - OPN (osteopontin) is a secreted glycoprotein predominantly expressed in bone
      matrix and kidney tissue. More recently, a neuroprotective role has been
      attributed to this cytokine since it can be up-regulated by microglia in
      neurodegeneration and inflammation. We demonstrate the expression of OPN within
      primary cultured microglia. Microglia incubated in vitro with different
      concentrations (0.1 fM-1 nM) of recombinant OPN showed increased proliferation at
      10 fM. Moreover, conditioned medium of LLC-PK1 cells, a pig renal epithelial cell
      line and a known source of secreted OPN, more than doubled the rate of
      proliferation of microglia. Addition of an anti-OPN polyclonal antibody
      completely reversed this effect. Treatment with OPN dose-dependently also
      inhibited microglial superoxide production. In contrast, phagocytosis of
      fluorescent-labelled beads was enhanced by OPN. In conclusion, OPN shifts
      microglia, at least in vitro, to an alternative functional profile more fit to
      the immune-balanced microenvironment of the CNS (central nervous system).

PMID- 22974009
TI  - Vulnerology: a new term to describe the discipline of wound care.
AB  - Although wound healing is probably the most critical aspect of essential medical
      and surgical care, it has been neglected for a long time. With the tremendous
      surge over the last two decades in basic research, wound healing is emerging as a
      well-defined medical entity transcending existing specialties and subdivisions.
      In view of the multitude of health professionals interested in the field of
      wounds and wound healing, it seems reasonably warranted to group them under one
      and single appellation. We suggest 'vulnerology' as a new term to describe the
      discipline of wound care. 

PMID- 22974010
TI  - A systematic review of perceived barriers and motivators to physical activity
      after stroke.
AB  - BACKGROUND AND PURPOSE: Physical fitness is impaired after stroke, may contribute
      to disability, yet is amenable to improvement through regular physical activity.
      To facilitate uptake and maintenance of physical activity, it is essential to
      understand stroke survivors' perceived barriers and motivators. Therefore, we
      undertook a systematic review of perceived barriers and motivators to physical
      activity after stroke. METHODS: Electronic searches of EMBASE, Medline, CINAHL,
      and PsychInfo were performed. We included peer-reviewed journal articles, in
      English, between 1 January 1966 and 30 August 2010 reporting stroke survivors'
      perceived barriers and motivators to physical activity. RESULTS: Searches
      identified 73,807 citations of which 57 full articles were retrieved. Six
      articles were included, providing data on 174 stroke survivors (range 10 to 83
      per article). Two reported barriers and motivators, two reported only motivators,
      and two reported only barriers. Five were qualitative articles and one was
      quantitative. The most commonly reported barriers were lack of motivation,
      environmental factors (e.g. transport), health concerns, and stroke impairments.
      The most commonly reported motivators were social support and the need to be able
      to perform daily tasks. CONCLUSION: This review has furthered our understanding
      of the perceived barriers and motivators to physical activity after a stroke.
      This review will enable the development of tailored interventions to target
      barriers, while building upon perceived motivators to increase and maintain
      stroke survivors' physical activity.

PMID- 22974012
TI  - Improving health outcomes through education.

PMID- 22974013
TI  - Physician complicity in the transformation of pain medicine from a "profession"
      to a "business": strategies for reversing a growing trend.

PMID- 22974011
TI  - MTOR signaling and ubiquitin-proteosome gene expression in the preservation of
      fat free mass following high protein, calorie restricted weight loss.
AB  - Caloric restriction is one of the most efficient ways to promote weight loss and
      is known to activate protective metabolic pathways. Frequently reported with
      weight loss is the undesirable consequence of fat free (lean muscle) mass loss.
      Weight loss diets with increased dietary protein intake are popular and may
      provide additional benefits through preservation of fat free mass compared to a
      standard protein, high carbohydrate diet. However, the precise mechanism by which
      a high protein diet may mitigate dietary weight loss induced reductions in fat
      free mass has not been fully elucidated. Maintenance of fat free mass is
      dependent upon nutrient stimulation of protein synthesis via the mTOR complex,
      although during caloric restriction a decrease (atrophy) in skeletal muscle may
      be driven by a homeostatic shift favouring protein catabolism. This review
      evaluates the relationship between the macronutrient composition of calorie
      restricted diets and weight loss using metabolic indicators. Specifically we
      evaluate the effect of increased dietary protein intake and caloric restricted
      diets on gene expression in skeletal muscle, particularly focusing on
      biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome
      (UPP) and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and
      S6K1.

PMID- 22974014
TI  - Dyschromatosis symmetrica hereditaria.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a rare pigmentary genodermatosis,
      which is acquired by autosomal dominant inheritance with high penetrance. Most
      cases of this condition have been reported from East Asian countries, including
      Japan, China and Taiwan. Its symptoms are mixed hyper- and hypopigmented macules
      on the dorsal aspect of the hands and feet and freckle-like macules on the face.
      The gene responsible for DSH has been identified as adenosine deaminase acting on
      RNA1 (ADAR1). The ADAR1 protein catalyzes the transformation of adenosine to
      inosine in dsRNA substrates (so-called A-to-I editing) and is involved in various
      activities, such as viral inactivation, structural change of the protein and the
      resultant cell survival. However, its function in the skin and role in the
      development of DSH are still unknown. To date, more than 100 mutations of ADAR1
      have been reported in patients with DSH, and the catalytic domain deaminase is
      believed to be crucial to the activities of this gene. Some complications of DSH
      have been reported and, intriguingly, several patients have been reported to
      develop neurological symptoms, such as dystonia and mental deterioration. Because
      ADAR1 plays various important roles in human tissue, we believe that a
      clarification of the pathogenesis of DSH will promote the understanding of the
      physiological functions of ADAR1, which will have significant scientific
      implications.

PMID- 22974015
TI  - Modeling copper binding to the amyloid-beta peptide at different pH: toward a
      molecular mechanism for Cu reduction.
AB  - Oxidative stress, including the production of reactive oxygen species (ROS), has
      been reported to be a key event in the etiology of Alzheimer's disease (AD). Cu
      has been found in high concentrations in amyloid plaques, a hallmark of AD, where
      it is bound to the main constituent amyloid-beta (Abeta) peptide. Whereas it has
      been proposed that Cu-Abeta complexes catalyze the production of ROS via redox
      cycling between the Cu(I) and Cu(II) state, the redox chemistry of Cu-Abeta and
      the precise mechanism of redox reactions are still unclear. Because experiments
      indicate different coordination environments for Cu(II) and Cu(I), it is expected
      that the electron is not transferred between Cu-Abeta and reactants in a
      straightforward manner but involves structural rearrangement. In this work the
      structures indicated by experimental data are modeled at the level of modern
      density-functional theory approximations. Possible pathways for Cu(II) reduction
      in different coordination sites are investigated by means of first-principles
      molecular dynamics simulations in the water solvent and at room temperature. The
      models of the ligand reorganization around Cu allow the proposal of a
      preferential mechanism for Cu-Abeta complex reduction at physiological pH. Models
      reveal that for efficient reduction the deprotonated amide N in the Ala 2-Glu 3
      peptide bond has to be protonated and that interactions in the second
      coordination sphere make important contributions to the reductive pathway, in
      particular the interaction between COO(-) and NH(2) groups of Asp 1. The proposed
      mechanism is an important step forward to a clear understanding of the redox
      chemistry of Cu-Abeta, a difficult task for spectroscopic approaches as the Cu
      peptide interactions are weak and dynamical in nature.

PMID- 22974016
TI  - NMR and computational studies of the configurational properties of
      spirodioxyselenuranes. Are dynamic exchange processes or temperature-dependent
      chemical shifts involved?
AB  - Spirodioxyselenurane 4a and several substituted analogs revealed unexpected (1)H
      NMR behavior. The diastereotopic methylene hydrogens of 4a appeared as an AB
      quartet at low temperature that coalesced to a singlet upon warming to 267 K,
      suggesting a dynamic exchange process with a relatively low activation energy.
      However, DFT computational investigations indicated high activation energies for
      exchange via inversion through the selenium center and for various pseudorotation
      processes. Moreover, the NMR behavior was unaffected by the presence of water or
      acid catalysts, thereby ruling out reversible Se-O or benzylic C-O cleavage as
      possible stereomutation pathways. Remarkably, when 4a was heated beyond 342 K,
      the singlet was transformed into a new AB quartet. Further computations indicated
      that a temperature dependence of the chemical shifts of the diastereotopic
      protons results in convergence upon heating, followed by crossover and divergence
      at still higher temperatures. The NMR behavior is therefore not due to dynamic
      exchange processes, but rather to temperature dependence of the chemical shifts
      of the diastereotopic hydrogens, which are coincidentally equivalent at
      intermediate temperatures. These results suggest the general need for caution in
      ascribing the coalescence of variable-temperature NMR signals of diastereotopic
      protons to dynamic exchange processes that could instead be due to temperature
      dependent chemical shifts and highlight the importance of corroborating
      postulated exchange processes through additional computations or experiments
      wherever possible.

PMID- 22974017
TI  - Genomic inheritances: disclosing individual research results from whole-exome
      sequencing to deceased participants' relatives.
AB  - Whole-genome analysis and whole-exome analysis generate many more clinically
      actionable findings than traditional targeted genetic analysis. These findings
      may be relevant to research participants themselves as well as for members of
      their families. Though researchers performing genomic analyses are likely to find
      medically significant genetic variations for nearly every research participant,
      what they will find for any given participant is unpredictable. The ubiquity and
      diversity of these findings complicate questions about disclosing individual
      genetic test results. We outline an approach for disclosing a select range of
      genetic results to the relatives of research participants who have died,
      developed in response to relatives' requests during a pilot study of large-scale
      medical genetic sequencing. We also argue that studies that disclose individual
      research results to participants should, at a minimum, passively disclose
      individual results to deceased participants' relatives.

PMID- 22974018
TI  - Beneficence, clinical urgency, and the return of individual research results to
      relatives.

PMID- 22974019
TI  - Disclosing individual genetic research results to deceased participants'
      relatives by means of a qualified disclosure policy.

PMID- 22974020
TI  - Risks to relatives in genomic research: a duty to warn?

PMID- 22974021
TI  - Disclosure/disruption: considering why not to disclose genetic information after
      death.

PMID- 22974022
TI  - Disclosing decedents' research results to relatives violates the HIPAA Privacy
      Rule.

PMID- 22974023
TI  - Clinically significant? Depends on whom you ask.

PMID- 22974024
TI  - Disclosing results to genomic research participants: differences that matter.

PMID- 22974025
TI  - The ever-evolving concept of clinical significance and the potential for sins of
      omission in genetic research.

PMID- 22974026
TI  - Rethinking clinical risk for DNA sequencing.

PMID- 22974027
TI  - Blurring boundaries.

PMID- 22974028
TI  - Surrogate decision making in the internet age.
AB  - The computer revolution has had an enormous effect on all aspects of the practice
      of medicine, yet little thought has been given to the role of social media in
      identifying treatment choices for incompetent patients. We are currently living
      in the "Internet age" and many people have integrated social media into all
      aspects of their lives. As use becomes more prevalent, and as users age, social
      media are more likely to be viewed as a source of information regarding medical
      care preferences. This article explores the ethical and legal issues raised by
      the use of social media in surrogate decision making.

PMID- 22974029
TI  - Surrogate decision making 2.0: digital evidence as clinical testimony.

PMID- 22974030
TI  - A disability response to surrogate decision making in the internet age.

PMID- 22974031
TI  - The self, social media, and social construction.

PMID- 22974032
TI  - Authenticating an online identity.

PMID- 22974033
TI  - Claims about surrogate decision-making accuracy require empirical evidence.

PMID- 22974034
TI  - Facebook can improve surrogate decision making.

PMID- 22974035
TI  - Social media as a contributor to substituted judgment: the hazards outweigh the
      value.

PMID- 22974036
TI  - Are we prepared for surrogate decision making in the internet age?

PMID- 22974037
TI  - Status update: the complexities of the internet age bring urgency for
      deliberately making advance health care decision wishes known.

PMID- 22974038
TI  - Considerations in surrogate decision making in the internet age.

PMID- 22974042
TI  - Response to open peer commentaries on "Surrogate decision making in the internet
      age".

PMID- 22974043
TI  - Biodegradable stents for caustic esophageal strictures: a new therapeutic
      approach.
AB  - The treatment of caustic esophageal strictures is a challenging topic. Although
      traditional therapies have limited efficacy, most of these patients eventually
      require surgery. Biodegradable (BD) stents are newly designed stents for benign
      conditions. This is a retrospective case series of seven patients with caustic
      esophageal stricture. BD esophageal stents were inserted for palliation of
      dysphagia. The position of the stent was checked at 1, 4, 8, 12 16, 20, and 24
      weeks and at the end of follow-up period. The follow-up period was 60 +/- 23 (36
      102) weeks. Complete dissolution of the stent occurred at 16 +/- 4 (12-20) weeks.
      Three patients had partial/complete relief of dysphagia. The remaining four
      patients experienced tissue hyperplasia at the edges of the stent and required
      serial dilations. At the end of follow-up, all patients had partial or complete
      relief of dysphagia. Although BD stents have some efficiency, tissue hyperplasia
      is the main limiting factor. Further randomized trials are needed to determine
      efficiency of BD stents for caustic damage.

PMID- 22974044
TI  - Cervicothoracic spinal cord and pontomedullary injury secondary to high-voltage
      electrocution: a case report.
AB  - INTRODUCTION: High-voltage electrical injuries are uncommonly reported and may
      predispose to both immediate and delayed neurologic complications. CASE
      PRESENTATION: We report the case of a 43-year-old Caucasian man who experienced a
      high-voltage electrocution injury resulting in ischemic myelopathy and secondary
      paraparesis. CONCLUSION: High-voltage electrocution injuries are a serious
      problem with potential for both immediate and delayed neurologic sequelae. The
      existing literature regarding effective treatment of neurologic complications is
      limited. Long-term follow-up and multidisciplinary management of these patients
      is required.

PMID- 22974045
TI  - Intake of omega-3 and omega-6 fatty acids and risk of basal and squamous cell
      carcinomas of the skin: a longitudinal community-based study in Australian
      adults.
AB  - Intake of omega-3 and omega-6 fatty acids may modify the risk of basal and
      squamous cell carcinoma of the skin (BCC and SCC), but population-based evidence
      is limited and inconsistent. We examined prospectively associations between
      intake of omega-3 and omega-6 fatty acids estimated from food frequency
      questionnaires and BCC and SCC incidence among 1322 randomly selected adults in
      Nambour, Australia. Relative risks (RR) and 95% confidence intervals (CI) were
      estimated based on histologically confirmed tumors diagnosed between 1997 and
      2007. Incidence of BCC was lowest in the middle third of both total omega-6
      intake (RR(mv.adj) = 0.74, 95% CI = 0.56-0.97) and linoleic acid intake
      (RR(mv.adj) = 0.75, 95% CI = 0.57-0.99) compared with the lowest third of intake.
      Evidence for associations with SCC was weak, though persons with arachidonic acid
      intake in the middle third had a marginally increased risk of SCC (RR(mv.adj) =
      1.42, 95% CI = 1.00-2.02). Consumption of omega-3 fatty acids was not associated
      with subsequent skin cancer risk. Suggestion that intake of arachidonic acid may
      be associated with increased SCC incidence and total omega-6 with reduced BCC
      from our study is still highly uncertain and may be due to chance. These data do
      not support an association between these fatty acids and risk of BCC or SCC.

PMID- 22974046
TI  - Psychiatrists' knowledge, training and attitudes regarding the care of
      individuals with intellectual disability.
AB  - BACKGROUND: Psychiatrists are responsible for providing proper care for people
      with intellectual disability who have psychiatric disorders. This study examined
      psychiatrists' perceptions of their own training, knowledge and therapeutic
      skills, as well as their attitudes towards this population. METHODS:
      Questionnaires were distributed to 679 psychiatrists working within the public
      sector in Israel. RESULTS: Completed questionnaires were returned from 256
      psychiatrists (38% response rate). Most (90%) participants reported having had
      limited training in the diagnosis and treatment of people with intellectual
      disabilities, while between 34% and 72% reported having inadequate knowledge in
      specific areas. CONCLUSION: The findings of limited training and self-perceived
      inadequate knowledge are at least partially explained by the service model,
      wherein people with intellectual disabilities are cared for by general mental
      health services. The identified inadequacies could be overcome through the
      implementation of a model in which specially trained psychiatrists are deployed
      within generic services.

PMID- 22974047
TI  - Absolute Hounsfield unit measurement on noncontrast computed tomography cannot
      accurately predict struvite stone composition.
AB  - BACKGROUND: The purpose of our study was to determine, in vivo, whether single
      energy noncontrast computed tomography (NCCT) can accurately predict the
      presence/percentage of struvite stone composition. METHODS: We retrospectively
      searched for all patients with struvite components on stone composition analysis
      between January 2008 and March 2012. Inclusion criteria were NCCT prior to stone
      analysis and stone size >=4 mm. A single urologist, blinded to stone composition,
      reviewed all NCCT to acquire stone location, dimensions, and Hounsfield unit
      (HU). HU density (HUD) was calculated by dividing mean HU by the stone's largest
      transverse diameter. Stone analysis was performed via Fourier transform infrared
      spectrometry. Independent sample Student's t-test and analysis of variance
      (ANOVA) were used to compare HU/HUD among groups. Spearman's correlation test was
      used to determine the correlation between HU and stone size and also HU/HUD to %
      of each component within the stone. Significance was considered if p<0.05.
      RESULTS: Fourty-four patients met the inclusion criteria. Struvite was the most
      prevalent component with mean percentage of 50.1%+/-17.7%. Mean HU and HUD were
      820.2+/-357.9 and 67.5+/-54.9, respectively. Struvite component analysis revealed
      a nonsignificant positive correlation with HU (R=0.017; p=0.912) and negative
      with HUD (R=-0.20; p=0.898). Overall, 3 (6.8%) had <20% of struvite component; 11
      (25%), 25 (56.8%), and 5 (11.4%) had 21% to 40%, 41% to 60%, and 61% to 80% of
      struvite, respectively. ANOVA revealed no difference among groups regarding HU
      (p=0.68) and HUD (p=0.37), with important overlaps. When comparing pure struvite
      stones (n=5) with other miscellaneous stones (n=39), no difference was found for
      HU (p=0.09) but HUD was significantly lower for pure stones (27.9+/-23.6 v 72.5+/
      55.9, respectively; p=0.006). Again, significant overlaps were seen. CONCLUSIONS:
      Pure struvite stones have significantly lower HUD than mixed struvite stones, but
      overlap exists. A low HUD may increase the suspicion for a pure struvite
      calculus.

PMID- 22974048
TI  - Chronic leg ulcers as a rare cause for the first diagnosis of epidermolysis
      bullosa dystrophica.
AB  - Chronic leg ulcers occur most frequently in the elderly population as a result of
      an underlying vascular disease especially chronic venous insufficiency. But it
      also occurs less commonly in younger people due to other aetiologies, for
      example, infections, vasculitis, neoplasia or genetic diseases. The following
      case report presents chronic leg ulcers as a rare cause for the first diagnosis
      of dystrophic epidermolysis bullosa. We report about a 21-year-old man with
      painful chronic leg ulcers resistant to different wound treatments for 4 months.
      After exclusion of the more common vascular aetiologies and reviewing the
      patient's family history, we considered an epidermolysis bullosa dystrophica
      which could be confirmed by genetic analyses. We treated the patient with
      debridement, modified negative pressure therapy with non-adhesive foil and skin
      grafting. The chronic leg ulcers healed completely. This case report demonstrates
      that the family history and genetic diseases should be considered as rare causes
      for therapy-refractory chronic leg ulcers, especially in young patients. 

PMID- 22974049
TI  - Susceptibility genes and pharmacogenetics in ocular inflammatory disorders.
AB  - Ocular inflammatory disorders encompass uveitis, scleritis, keratitis, and other
      ocular diseases where inflammation may play a role. Although age-related macular
      degeneration (AMD) is clinically characterized by degenerative changes in the
      macula, accumulating evidence suggests that inflammation plays an important role
      in its pathogenesis. Pharmacogenetics is the study of the influence of genetic
      variation and its effects on drug efficacy or toxicity. There are no
      pharmacogenetic studies in uveitis and very few in AMD therapies. In this review,
      the authors describe the susceptibility genes related to uveitis and AMD and the
      important advances in pharmacogenetic research in relation to AMD and uveitis
      therapy. They propose polygenic and composite models of treatment responses to
      fulfill individualized drug therapy in intraocular inflammatory disorders.

PMID- 22974050
TI  - A longitudinal cohort study on quality of life in stroke patients and their
      partners: Restore4Stroke Cohort.
AB  - BACKGROUND: Stroke is a major cause of disability in the Western world. Its long
      term consequences have a negative impact on the quality of life of both the
      patients and their partners. AIM: The aim of the Restore4Stroke Cohort study is
      to investigate the changes in quality of life of stroke patients and their
      partners over time, and to determine factors predicting quality of life in
      several domains, especially personal and environmental factors. METHOD:
      Multicentre prospective longitudinal cohort study. Inclusion and the first
      assessment take place during hospital stay in the first week post-stroke. Follow
      up assessments take place at two months, six months, one year, and two years post
      stroke. Recruitment of 500 patients from stroke units in six participation
      hospitals is foreseen. If the patient has a partner, he or she is also asked to
      participate in the study. OUTCOMES: The main outcome is quality of life,
      considered from a health-related quality of life and domain-specific quality of
      life perspective. Factors predicting long-term quality of life will be determined
      by taking into account the health condition (pre-stroke health condition and
      stroke-related health condition), personal factors (e.g. coping and illness
      cognitions), and environmental factors (e.g. caregiver burden and social
      support). DISCUSSION: This study is expected to provide information about the
      changes in quality of life of stroke patients and their partners over time.
      Furthermore, the identification of factors predicting quality of life can be used
      to improve rehabilitation care and develop new interventions for stroke patients
      and their partners.

PMID- 22974051
TI  - Automatic classification of protein structures relying on similarities between
      alignments.
AB  - BACKGROUND: Identification of protein structural cores requires isolation of sets
      of proteins all sharing a same subset of structural motifs. In the context of an
      ever growing number of available 3D protein structures, standard and automatic
      clustering algorithms require adaptations so as to allow for efficient
      identification of such sets of proteins. RESULTS: When considering a pair of 3D
      structures, they are stated as similar or not according to the local similarities
      of their matching substructures in a structural alignment. This binary relation
      can be represented in a graph of similarities where a node represents a 3D
      protein structure and an edge states that two 3D protein structures are similar.
      Therefore, classifying proteins into structural families can be viewed as a graph
      clustering task. Unfortunately, because such a graph encodes only pairwise
      similarity information, clustering algorithms may include in the same cluster a
      subset of 3D structures that do not share a common substructure. In order to
      overcome this drawback we first define a ternary similarity on a triple of 3D
      structures as a constraint to be satisfied by the graph of similarities. Such a
      ternary constraint takes into account similarities between pairwise alignments,
      so as to ensure that the three involved protein structures do have some common
      substructure. We propose hereunder a modification algorithm that eliminates edges
      from the original graph of similarities and gives a reduced graph in which no
      ternary constraints are violated. Our approach is then first to build a graph of
      similarities, then to reduce the graph according to the modification algorithm,
      and finally to apply to the reduced graph a standard graph clustering algorithm.
      Such method was used for classifying ASTRAL-40 non-redundant protein domains,
      identifying significant pairwise similarities with Yakusa, a program devised for
      rapid 3D structure alignments. CONCLUSIONS: We show that filtering similarities
      prior to standard graph based clustering process by applying ternary similarity
      constraints i) improves the separation of proteins of different classes and
      consequently ii) improves the classification quality of standard graph based
      clustering algorithms according to the reference classification SCOP.

PMID- 22974052
TI  - Size-dependent uptake of silver nanoparticles in Daphnia magna.
AB  - The toxicity of silver nanoparticles (AgNPs) has been widely investigated, but
      the process of bioaccumulation such as uptake remains less studied. In the
      present study, we employed the radioisotope ((110m)Ag) to trace the behaviors of
      commercial AgNPs with three nominal particle sizes (20, 50, and 100 nm) and two
      surface coatings (citrate and tannic acid) in a model organism Daphnia magna .
      The size distributions of AgNPs in the medium increased continuously as the
      exposure time increased, especially for the smallest AgNPs (20 nm). Cysteine, the
      amino acid containing thiol group, significantly enhanced particle aggregation,
      with a 30-fold increase of the hydrodynamic size for AgNPs with 20 nm nominal
      size after 6 h of exposure. We demonstrated that the influx rates of AgNPs into
      daphnids were size-dependent. At 500 MUg/L AgNPs with 1 MUM cysteine, the influx
      rates of AgNPs were in the sequence 20 nm > 50 nm > 100 nm (nominal size) for
      both types of surface coatings. Such sequence was consistent with the size
      distribution in the medium. More than 60% of AgNPs were distributed in the gut of
      daphnids, indicating that ingestion was the dominant uptake pathway. The size
      dependent influx rate was also observed at different AgNPs concentrations. The
      measured uptake rate constant was lower than that of AgNO(3) at low AgNPs
      concentration, but it became higher at high AgNPs concentrations. Our study
      highlighted the indispensability of characterizing the size distribution of AgNPs
      dispersed in the medium in studying the AgNPs uptake. The accurate quantification
      of AgNPs influx rate suggested an uptake pathway entirely different from that of
      AgNO(3) in the daphnids.

PMID- 22974053
TI  - Evidence that a transient but cognitively demanding process underlies forward
      blocking.
AB  - Blocking is a learning phenomenon in which prior experience inhibits learning
      about novel cues. Though the phenomenon itself has been well documented, the
      details of blocking-related processes still remain contentious. Two experiments
      investigated whether participants were engaged in demanding cognitive processing
      during different portions of a standard blocking paradigm. Participants in
      Experiment 1 engaged in a simple secondary task while completing a standard
      blocking procedure. Results showed that performance on the secondary task was
      briefly diminished early in the second phase of the blocking paradigm, when the
      novel cue is first paired with the pretrained cue. Participants in Experiment 2
      performed a difficult cognitive load task during either the early or the late
      portions of the second phase of blocking. The blocking effect was eliminated when
      learners were under load early in the second phase, but not when learners were
      under load late in the second phase. These results suggest that blocking relies
      on a cognitively demanding process with a distinct time course. Computational
      simulations illustrate how a model that includes top-down (i.e., cognitively
      demanding) attentional modulation can reproduce the observed behaviour. This
      suggests that purely associative processes are not sufficient to explain the
      observed behaviour. Implications for current accounts of blocking are discussed.

PMID- 22974054
TI  - von Willebrand factor: factor VIII protector and friend.

PMID- 22974056
TI  - Polymer-fullerene miscibility: a metric for screening new materials for high
      performance organic solar cells.
AB  - The improvement of the power conversion efficiency (PCE) of polymer bulk
      heterojunction (BHJ) solar cells has generally been achieved through synthetic
      design to control frontier molecular orbital energies and molecular ordering of
      the electron-donating polymer. An alternate approach to control the PCE of a BHJ
      is to tune the miscibility of the fullerene and a semiconducting polymer by
      varying the structure of the fullerene. The miscibility of a series of 1,4
      fullerene adducts in the semiconducting polymer, poly(3-hexylselenophene), P3HS,
      was measured by dynamic secondary ion mass spectrometry using a model bilayer
      structure. The microstructure of the bilayer was investigated using high-angle
      annular dark-field scanning transmission microscopy and linked to the polymer
      fullerene miscibility. Finally, P3HS:fullerene BHJ solar cells were fabricated
      from each fullerene derivative, enabling the correlation of the active layer
      microstructure to the charge collection efficiency and resulting PCE of each
      system. The volume fraction of polymer-rich, fullerene-rich, and polymer
      fullerene mixed domains can be tuned using the miscibility leading to improvement
      in the charge collection efficiency and PCE in P3HS:fullerene BHJ solar cells.
      These results suggest a rational approach to the design of fullerenes for
      improved BHJ solar cells.

PMID- 22974055
TI  - Excitability decreasing central motor plasticity is retained in multiple
      sclerosis patients.
AB  - BACKGROUND: Compensation of brain injury in multiple sclerosis (MS) may in part
      work through mechanisms involving neuronal plasticity on local and interregional
      scales. Mechanisms limiting excessive neuronal activity may have special
      significance for retention and (re-)acquisition of lost motor skills in brain
      injury. However, previous neurophysiological studies of plasticity in MS have
      investigated only excitability enhancing plasticity and results from neuroimaging
      are ambiguous. Thus, the aim of this study was to probe long-term depression-like
      central motor plasticity utilizing continuous theta-burst stimulation (cTBS), a
      non-invasive brain stimulation protocol. Because cTBS also may trigger behavioral
      effects through local interference with neuronal circuits, this approach also
      permitted investigating the functional role of the primary motor cortex (M1) in
      force control in patients with MS. METHODS: We used cTBS and force recordings to
      examine long-term depression-like central motor plasticity and behavioral
      consequences of a M1 lesion in 14 patients with stable mild-to-moderate MS
      (median EDSS 1.5, range 0 to 3.5) and 14 age-matched healthy controls. cTBS
      consisted of bursts (50 Hz) of three subthreshold biphasic magnetic stimuli
      repeated at 5 Hz for 40 s over the hand area of the left M1. Corticospinal
      excitability was probed via motor-evoked potentials (MEP) in the abductor
      pollicis brevis muscle over M1 before and after cTBS. Force production
      performance was assessed in an isometric right thumb abduction task by recording
      the number of hits into a predefined force window. RESULTS: cTBS reduced MEP
      amplitudes in the contralateral abductor pollicis brevis muscle to a comparable
      extent in control subjects (69 +/- 22% of baseline amplitude, p < 0.001) and in
      MS patients (69 +/- 18%, p < 0.001). In contrast, post-cTBS force production
      performance was only impaired in controls (2.2 +/- 2.8, p = 0.011), but not in MS
      patients (2.0 +/- 4.4, p = 0.108). The decline in force production performance
      following cTBS correlated with corticomuscular latencies (CML) in MS patients,
      but did not correlate with MEP amplitude reduction in patients or controls.
      CONCLUSIONS: Long-term depression-like plasticity remains largely intact in mild
      to-moderate MS. Increasing brain injury may render the neuronal networks less
      responsive toward lesion-induction by cTBS.

PMID- 22974057
TI  - Stop codons in bacteria are not selectively equivalent.
AB  - BACKGROUND: The evolution and genomic stop codon frequencies have not been
      rigorously studied with the exception of coding of non-canonical amino acids.
      Here we study the rate of evolution and frequency distribution of stop codons in
      bacterial genomes. RESULTS: We show that in bacteria stop codons evolve slower
      than synonymous sites, suggesting the action of weak negative selection. However,
      the frequency of stop codons relative to genomic nucleotide content indicated
      that this selection regime is not straightforward. The frequency of TAA and TGA
      stop codons is GC-content dependent, with TAA decreasing and TGA increasing with
      GC-content, while TAG frequency is independent of GC-content. Applying a formal,
      analytical model to these data we found that the relationship between stop codon
      frequencies and nucleotide content cannot be explained by mutational biases or
      selection on nucleotide content. However, with weak nucleotide content-dependent
      selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and
      recapitulates the relationship between TAG and nucleotide content. For
      biologically plausible rates of mutations we show that, in bacteria, TAG stop
      codon is universally associated with lower fitness, with TAA being the optimal
      for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.
      CONCLUSIONS: Our data indicate that TAG codon is universally suboptimal in the
      bacterial lineage, such that TAA is likely to be the preferred stop codon for low
      GC content while the TGA is the preferred stop codon for high GC content. The
      optimization of stop codon usage may therefore be useful in genome engineering or
      gene expression optimization applications.

PMID- 22974058
TI  - Notch signalling inhibits the adipogenic differentiation of single-cell-derived
      mesenchymal stem cell clones isolated from human adipose tissue.
AB  - ADSCs (adipose-derived mesenchymal stem cells) are candidate adult stem cells for
      regenerative medicine. Notch signalling participates in the differentiation of a
      heterogeneous ADSC population. We have isolated, human adipose tissue-derived
      single-cell clones using a cloning ring technique and characterized for their
      stem cell characteristics. The role of Notch signalling in the differentiation
      capacity of these adipose-derived single-cell-clones has also been investigated.
      All 14 clones expressed embryonic and mesenchymal stem cell marker genes. These
      clones could differentiate into both osteogenic and adipogenic lineages. However,
      the differentiation potential of each clone was different. Low adipogenic clones
      had significantly higher mRNA expression levels of Notch 2, 3 and 4, Jagged1, as
      well as Delta1, compared with those of high adipogenic clones. In contrast, no
      changes in expression of Notch signalling component mRNA between low and high
      osteogenic clones was found. Notch receptor mRNA expression decreased with the
      adipogenic differentiation of both low and high adipogenic clones. The gamma
      secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-(S)
      phenylglycine t-butyl ester), enhanced adipogenic differentiation.
      Correspondingly, cells seeded on a Notch ligand (Jagged1) bound surface showed
      lower intracellular lipid accumulation. These results were noted in both low and
      high adipogenic clones, indicating that Notch signalling inhibited the adipogenic
      differentiation of adipose ADSC clones, and could be used to identify an
      adipogenic susceptible subpopulation for soft-tissue augmentation application.

PMID- 22974060
TI  - Two cases of livedo vasculopathy with non-criteria antiphospholipid antibodies.
AB  - Livedo vasculopathy is characterized by reticular distribution of purpuric
      macules and papules of the lower legs, caused by intraluminal thrombosis of small
      vessels. Antiphospholipid antibodies are detected in a subset of these patients.
      We treated two cases (a 34-year-old man and a 46-year-old woman) with livedo
      vasculopathy. In both cases, thrombosis was seen only in the skin. The presence
      of immunoglobulin (Ig)G or IgM anticardiolipin antibody (Ab), IgG or IgM anti
      beta(2) -glycoprotein I Ab, or lupus anticoagulant are necessary for criteria
      based diagnosis of antiphospholipid syndrome. However, our patients were negative
      for these Ab, and instead had either IgG antiphosphatidylethanolamine Ab or IgA
      anticardiolipin Ab. These Ab are suggestive of antiphospholipid syndrome but are
      not considered "criteria" Ab. This report demonstrates the existence of
      antiphosphatidylethanolamine Ab or IgA anticardiolipin Ab in patients with livedo
      vasculopathy. However, the frequency and significance of these Ab in livedo
      vasculopathy should be confirmed in larger longitudinal studies.

PMID- 22974059
TI  - Role of bicarbonate as a pH buffer and electron sink in microbial dechlorination
      of chloroethenes.
AB  - BACKGROUND: Buffering to achieve pH control is crucial for successful
      trichloroethene (TCE) anaerobic bioremediation. Bicarbonate (HCO3-) is the
      natural buffer in groundwater and the buffer of choice in the laboratory and at
      contaminated sites undergoing biological treatment with organohalide respiring
      microorganisms. However, HCO3- also serves as the electron acceptor for
      hydrogenotrophic methanogens and hydrogenotrophic homoacetogens, two microbial
      groups competing with organohalide respirers for hydrogen (H2). We studied the
      effect of HCO3- as a buffering agent and the effect of HCO3--consuming reactions
      in a range of concentrations (2.5-30 mM) with an initial pH of 7.5 in H2-fed TCE
      reductively dechlorinating communities containing Dehalococcoides,
      hydrogenotrophic methanogens, and hydrogenotrophic homoacetogens. RESULTS: Rate
      differences in TCE dechlorination were observed as a result of added varying HCO3
      concentrations due to H2-fed electrons channeled towards methanogenesis and
      homoacetogenesis and pH increases (up to 8.7) from biological HCO3- consumption.
      Significantly faster dechlorination rates were noted at all HCO3- concentrations
      tested when the pH buffering was improved by providing 4-(2-hydroxyethyl)-1
      piperazineethanesulfonic acid (HEPES) as an additional buffer. Electron balances
      and quantitative PCR revealed that methanogenesis was the main electron sink when
      the initial HCO3- concentrations were 2.5 and 5 mM, while homoacetogenesis was
      the dominant process and sink when 10 and 30 mM HCO3- were provided initially.
      CONCLUSIONS: Our study reveals that HCO3- is an important variable for
      bioremediation of chloroethenes as it has a prominent role as an electron
      acceptor for methanogenesis and homoacetogenesis. It also illustrates the changes
      in rates and extent of reductive dechlorination resulting from the combined
      effect of electron donor competition stimulated by HCO3- and the changes in pH
      exerted by methanogens and homoacetogens.

PMID- 22974062
TI  - A test of order-constrained hypotheses for circular data with applications to
      human movement science.
AB  - Researchers studying the movements of the human body often encounter data
      measured in angles (e.g., angular displacements of joints). The evaluation of
      these circular data requires special statistical methods. The authors introduce a
      new test for the analysis of order-constrained hypotheses for circular data.
      Through this test, researchers can evaluate their expectations regarding the
      outcome of an experiment directly by representing their ideas in the form of a
      hypothesis containing inequality constraints. The resulting data analysis is
      generally more powerful than one using standard null hypothesis testing. Two
      examples of circular data from human movement science are presented to illustrate
      the use of the test. Results from a simulation study show that the test performs
      well.

PMID- 22974061
TI  - Is body mass index a useful measure of excess body fatness in adolescents and
      young adults with Down syndrome?
AB  - BACKGROUND: To determine the validity of body mass index (BMI) to identify excess
      fatness in youth with Down syndrome (DS). METHODS: Using the Centers for Disease
      Control and Prevention (CDC) growth reference, we defined overweight (>= 85th
      percentile) and obesity (>= 95th percentile) based on participants' age- and sex
      specific BMI z-scores, calculated from measured height and weight. Percentage
      body fat was measured by dual-energy X-ray absorptiometry. We determined
      sensitivity, specificity, positive predictive value, negative predictive value
      and efficiency of BMI percentiles to identify excess adiposity relative to
      elevated percentage body fat cut-offs developed from the Pediatric Rosetta Body
      Composition project in 32 youth (20 boys/12 girls), ages 13-21 years with Down
      syndrome. RESULTS: For adolescents with Down syndrome using the cut-off points of
      95th percentile for BMI (obesity), sensitivity and specificity were 71% and 96%
      respectively. Positive predictive value was 83% and negative predictive value was
      92%. Overall efficiency was 91%. Sensitivity and specificity for BMI cut-offs
      above the 85th percentile (overweight) were 100% and 60% respectively. The
      positive predictive value was 41% and negative predictive value was 100%. Overall
      efficiency was 69%. CONCLUSION: On the whole, the obesity (>= 95th percentile)
      cut-off performs better than the overweight cut-off (85th-94th percentile) in
      identifying elevated fatness in youth with DS.

PMID- 22974064
TI  - Transient Rayleigh scattering: a new probe of picosecond carrier dynamics in a
      single semiconductor nanowire.
AB  - Using a new technique, transient Rayleigh scattering, we show that measurements
      from a single GaAs/AlGaAs core-shell semiconductor nanowire provide sensitive and
      detailed information on the time evolution of the density and temperature of the
      electrons and holes after photoexcitation by an intense laser pulse. Through band
      filling, band gap renormalization, and plasma screening, the presence of a dense
      and hot electron-hole plasma directly influences the real and imaginary parts of
      the complex index of refraction that in turn affects the spectral dependence of
      the Rayleigh scattering cross-section in well-defined ways. By measuring this
      spectral dependence as a function of time, we directly determine the
      thermodynamically independent density and temperature of the electrons and holes
      as a function of time after pulsed excitation as the carriers thermalize to the
      lattice temperature. We successfully model the results by including ambipolar
      transport, recombination, and cooling through optic and acoustic phonon emission
      that quantify the hole mobility at ~68,000 cm(2)/V.s, linear decay constant at
      380 ps, bimolecular recombination rate at 4.8 * 10(-9) cm(3)/s and the energy
      loss rate of plasma due to optical and acoustic phonon emission.

PMID- 22974063
TI  - Stereoselective N-glycosylation of 2-deoxythioribosides for fluorescent
      nucleoside synthesis.
AB  - An efficient method for the N-2-deoxyribosylation of modified nucleobases by 2
      deoxythioriboside donors is reported. In the presence of an in situ silylated
      nucleobase, thioglycosides can be activated with NIS/HOTf to give nucleosides in
      high yields and with good beta-selectivity. By tuning the protecting groups on
      the C3 and C5 hydroxyls, alpha/beta ratios ranging from 1.0:4.0 to 4.5:1.0 can be
      obtained. This strategy is applicable to the synthesis of various nucleosides,
      including ring-expanded pyrimidine derivatives containing sulfur that have
      previously been reported in low yields. The utility of this approach is further
      demonstrated by the synthesis of fluorescent nucleosides analogues such as
      quinazoline and oxophenothiazine that should find broad utility in DNA-folding
      and recognition studies.

PMID- 22974065
TI  - Hypoganglionosis in pregnancy: a case report.
AB  - INTRODUCTION: We report a very rare case of isolated hypoganglionosis first
      diagnosed during early pregnancy, which should be discussed from an obstetric and
      a gastroenterological point of view. CASE PRESENTATION: A pregnant 18-year-old
      Caucasian woman presented at twelve weeks of gestation with lower abdominal pain,
      mild constipation and a large abdominal mass. Abdominal and pelvic magnetic
      resonance imaging demonstrated a megarectum and megasigmoid, and our patient was
      managed with medical therapy during her pregnancy, which occurred without major
      incidents. At the onset of labor, a fecaloma obstructing the pelvic outlet was
      detected, which required manual disimpaction. However, during the procedure a
      sudden continuous fetal bradycardia was detected. An emergency Cesarean section
      was performed but the fetus suffered hypoxic ischemic encephalopathy. One year
      after the delivery, our patient underwent a sigmoid resection. A
      histopathological analysis revealed a reduction of nerve cells in the myenteric
      and submucous plexus, suggesting hypoganglionosis. CONCLUSION: Although there are
      some reports of pregnancies complicated by megacolon, they are too few and too
      old to delineate guidelines for clinical orientation. In our article, we discuss
      several issues regarding the management of these rare intestinal innervation
      disorders during pregnancy that we believe will enhance their obstetric and
      gastroenterological management during pregnancy.

PMID- 22974066
TI  - Magnetically tunable elasticity for magnetic hydrogels consisting of carrageenan
      and carbonyl iron particles.
AB  - A new class of magnetoelastic gel that demonstrates drastic and reversible
      changes in storage modulus without using strong magnetic fields was obtained. The
      magnetic gel consists of carrageenan and carbonyl iron particles. The magnetic
      gel with a volume fraction of magnetic particles of 0.30 exhibited a reversible
      increase by a factor of 1400 of the storage modulus upon a magnetic field of 500
      mT, which is the highest value in the past for magnetorheological soft materials.
      It is considered that the giant magnetoelastic behavior is caused by both high
      dispersibility and high mobility of magnetic particles in the carrageenan gel.
      The off-field storage modulus of the magnetic gel at volume fractions below 0.30
      obeyed the Krieger-Dougherty equation, indicating random dispersion of magnetic
      particles. At 500 mT, the storage modulus was higher than 4.0 MPa, which is equal
      to that of magnetic fluids, indicating that the magnetic particles move and form
      a chain structure by magnetic fields. Morphological study revealed the evidence
      that the magnetic particles embedded in the gel were aligned in the direction of
      magnetic fields, accompanied by stretching of the gel network. We conclude that
      the giant magnetoelastic phenomenon originates from the chain structure
      consisting of magnetic particles similar to magnetic fluids.

PMID- 22974067
TI  - Electrical-thermal performance of a cooled RF applicator for hepatic ablation
      with additional distant infusion of hypertonic saline: in vivo study and
      preliminary computer modeling.
AB  - PURPOSE: The Cool-tip electrode is one of the most widely employed applicators in
      radiofrequency (RF) hepatic ablation. Previous research demonstrated that it is
      possible to enlarge coagulation volume when the single cooled electrode is
      associated with distant infusion of saline (hybrid applicator). The aim of this
      study was to compare the electrical-thermal behaviour of the Cool-tip electrode
      with that of the hybrid applicator. MATERIALS AND METHODS: Forty-two RF ablations
      were performed on a total of 10 pigs: 22 with the Cool-tip electrode and 20 with
      the hybrid applicator (low infused saline volumetric flow rate of 6 mL/h at 2 mm
      distance). We compared both electrical performance (delivered power and number of
      roll-offs, i.e. sudden rises in impedance that interrupt the power delivery) and
      coagulation zone characteristics. In addition, we built a one-dimensional model
      to provide a basic physical explanation of the difference in performance between
      the different applicators. RESULTS: The experimental results showed that the
      number of roll-offs with the Cool-tip electrode was higher (24.3 +/- 3.1 versus
      6.7 +/- 7.0). The hybrid applicator created larger coagulation volumes (19.7 +/-
      9.5 cm(3) versus 9.5 +/- 5.8 cm(3)) with larger transverse diameters (2.5 +/- 0.6
      versus 1.9 +/- 0.5 cm). The one-dimensional model confirmed the delay in the
      incidence of the first roll-off, but not the heterogeneity of the hybrid
      applicator's electrical performance in the experiments. CONCLUSIONS: The hybrid
      applicator produces fewer roll-off episodes than the Cool-tip electrode and
      creates larger coagulation volumes with larger transverse diameters.

PMID- 22974068
TI  - Biological pest control in Mexico.
AB  - Mexico is a megadiverse country that forms part of the Mesoamerican biological
      corridor that connects North and South America. Mexico's biogeographical
      situation places it at risk from invasive exotic insect pests that enter from the
      United States, Central America, or the Caribbean. In this review we analyze the
      factors that contributed to some highly successful past programs involving
      classical biological control and/or the sterile insect technique (SIT). The
      present situation is then examined with reference to biological control,
      including SIT programs, targeted at seven major pests, with varying degrees of
      success. Finally, we analyze the current threats facing Mexico's agriculture
      industry from invasive pests that have recently entered the country or are about
      to do so. We conclude that despite a number of shortcomings, Mexico is better set
      to develop biological control-based pest control programs, particularly on an
      area-wide basis, than many other Latin American countries are. Classical and
      augmentative biological control and SIT-based programs are likely to provide
      effective and sustainable options for control of native and exotic pests,
      particularly when integrated into technology packages that meet farmers' needs
      across the great diversity of production systems in Mexico.

PMID- 22974069
TI  - An emerging understanding of mechanisms governing insect herbivory under elevated
      CO2.
AB  - By changing the chemical composition of foliage, the increase in atmospheric
      CO(2) is fundamentally altering insect herbivory. The responses of folivorous
      insects to these changes is, however, highly variable. In this review we
      highlight emerging mechanisms by which increasing CO(2) alters the defense
      chemistry and signaling of plants. The response of allelochemicals affecting
      insect performance varies under elevated CO(2), and results suggest this is
      driven by changes in plant hormones. Increasing CO(2) suppresses the production
      of jasmonates and ethylene and increases the production of salicylic acid, and
      these differential responses of plant hormones affect specific secondary chemical
      pathways. In addition to changes in secondary chemistry, elevated CO(2) decreases
      rates of water loss from leaves, increases temperature and feeding rates, and
      alters nutritional content. New insights into the mechanistic responses of
      secondary chemistry to elevated CO(2) increase our ability to predict the
      ecological and evolutionary responses of plants attacked by insects.

PMID- 22974070
TI  - The burden of stroke in the Lao People's Democratic Republic.
AB  - In the Lao People's Democratic Republic (Laos), stroke is ranked as the third
      leading cause of death, with a 9.01% mortality rate. To date, neither the
      prevalence nor the incidence of stroke has been recorded in Laos. This omission
      may be attributed to a lack of awareness among Laotians of the signs and symptoms
      of stroke, incomplete data, or insufficient database recording. The only risk
      factor for stroke that has been studied extensively is cigarette smoking; studies
      have found that smokers have twice the risk of stroke. Unfortunately, smoking is
      increasing among youths, adults, and even healthcare professionals. The Southeast
      Asia Tobacco Control Alliance stated that 42% of hospitalized stroke patients are
      smokers. Laos is one of the least developed countries in the world, and the
      country has only one fully trained neurologist for the growing number of stroke
      cases. The Laos government should seek help from international bodies, such as
      the World Health Organization, to monitor and rehabilitate stroke patients and
      prevent stroke occurrence and recurrence.

PMID- 22974071
TI  - The pragmatic language abilities of children with ADHD following a play-based
      intervention involving peer-to-peer interactions.
AB  - Children with Attention Deficit Hyperactivity Disorder (ADHD) commonly experience
      significant pragmatic language deficits which put them at risk of developing
      emotional and social difficulties. This study aimed to examine the pragmatic
      language exhibited in a peer-to-peer interaction between the children with ADHD
      and their playmates following a pilot play-based intervention. Participants were
      children (aged 5-11 years) diagnosed as having ADHD (n = 14) and their self
      selected typically-developing playmate. Pragmatic language was measured using the
      Pragmatic Protocol (PP) and the Structured Multidimensional Assessment Profiles
      (S-MAPs). Children's structural language was also screened and compared against
      their pragmatic language skills pre-post play-based intervention. The pragmatic
      language of children with ADHD improved significantly from pre-post intervention
      as measured by both the PP and S-MAPs. Both children with and without structural
      language difficulties improved significantly from pre- to post-intervention using
      S-MAPs; only children with structural language difficulties improved
      significantly using PP. The findings support the notion that pragmatic skills may
      improve following a play-based intervention that is characterized by didactic
      social interaction. As pragmatic language is a complex construct, it is proposed
      that clinicians and researchers reconsider the working definition of pragmatic
      language and the operationalization thereof in assessments.

PMID- 22974072
TI  - Stuttering attitudes in Hong Kong and adjacent Mainland China.
AB  - The present study aims at studying the public attitudes towards stuttering in
      Hong Kong and Mainland China. Translated Chinese versions of the Public Opinion
      Survey of Human Attributes-Stuttering (POSHA-S) were distributed to convenience
      samples in Hong Kong and Mainland China, with a total number of 175 completed
      questionnaires returned in each sampling region (n 5 350). Mean ratings of
      respondents from Hong Kong and Mainland China were similar in most comparisons;
      yet, a few differences were noted. Larger but idiosyncratic differences
      characterized the Chinese respondents compared to more than 4000 respondents from
      numerous countries and languages around the world in the POSHA-S database
      archive. Overall, they documented aspects of stereotypes and potential stigma
      with respect to people who stutter. While premature to provide unambiguous
      conclusions, results suggest that Chinese respondents have unique stuttering
      attitudes.

PMID- 22974073
TI  - Dysphagia training for speech-language pathologists: implications for clinical
      practice.
AB  - There are competency standards available in countries with established speech
      language pathology services to guide basic dysphagia training with ongoing
      workplace mentoring for advanced skills development. Such training processes,
      however, are not as well established in countries where speech-language pathology
      training and practice is relatively new, such as Malaysia. The current study
      examines the extent of dysphagia training and workplace support available to
      speech-language pathologists (SLPs) in Malaysia and Queensland, Australia, and
      explores clinicians' perceptions of the training and support provided, and of
      their knowledge, skills, and confidence. Using a matched cohort cross-sectional
      design, a purpose-built survey was administered to 30 SLPs working in Malaysian
      government hospitals and 30 SLPs working in Queensland Health settings in
      Australia. Malaysian clinicians were found to have received significantly less
      university training, less mentoring in the workplace, and were lacking key
      infrastructure needed to support professional development in dysphagia
      management. Over 90% of Queensland clinicians were confident and felt they had
      adequate skills in dysphagia management; in contrast, significantly lower levels
      of knowledge, skills, and confidence were observed in the Malaysian cohort. The
      findings identify a need for improved university training and increased
      opportunities for workplace mentoring, training, and support for Malaysian SLPs.

PMID- 22974074
TI  - Phase II study of patients with peritoneal carcinomatosis from gastric cancer
      treated with preoperative systemic chemotherapy followed by peritonectomy and
      intraperitoneal chemotherapy.
AB  - BACKGROUND: The aim was to evaluate the feasibility and the effectiveness of
      neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS),
      hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative
      intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis
      (PC) from gastric cancer. MATERIAL AND METHODS: Eighteen patients (median age 57
      years, range 38-74) were scheduled for three months' neoadjuvant systemic
      chemotherapy followed by CRS + HIPEC + EPIC. RESULTS: At the time of surgery, the
      peritoneal tumor burden was extensive with tumor growth on the entire peritoneal
      cavity. Only eight patients received the entire treatment and OS was 14.3 months
      (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0)
      surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9
      27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative
      grades II-IV adverse events (AE) rate was 62.5%. DISCUSSION: Neoadjuvant
      chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with
      prolonged OS in patients with extensive PC growth from gastric cancer unless
      macroscopically radical surgery is achieved. However, morbidity from this
      treatment is considerable and it cannot be recommended for routine care until a
      prospective randomized trial has been performed.

PMID- 22974075
TI  - Greenhouse gas and criteria emission benefits through reduction of vessel speed
      at sea.
AB  - Reducing emissions from ocean-going vessels (OGVs) as they sail near populated
      areas is a widely recognized goal, and Vessel Speed Reduction (VSR) is one of
      several strategies that is being adopted by regulators and port authorities. The
      goal of this research was to measure the emission benefits associated with
      greenhouse gas and criteria pollutants by operating OGVs at reduced speed.
      Emissions were measured from one Panamax and one post-Panamax class container
      vessels as their vessel speed was reduced from cruise to 15 knots or below. VSR
      to 12 knots yielded carbon dioxide (CO(2)) and nitrogen oxides (NO(x)) emissions
      reductions (in kg/nautical mile (kg/nmi)) of approximately 61% and 56%,
      respectively, as compared to vessel cruise speed. The mass emission rate (kg/nmi)
      of PM(2.5) was reduced by 69% with VSR to 12 knots alone and by ~97% when coupled
      with the use of the marine gas oil (MGO) with 0.00065% sulfur content. Emissions
      data from vessels while operating at sea are scarce and measurements from this
      research demonstrated that tidal current is a significant parameter affecting
      emission factors (EFs) at lower engine loads. Emissions factors at <=20% loads
      calculated by methodology adopted by regulatory agencies were found to
      underestimate PM(2.5) and NO(x) by 72% and 51%, respectively, when compared to
      EFs measured in this study. Total pollutant emitted (TPE) in the emission control
      area (ECA) was calculated, and emission benefits were estimated as the VSR zone
      increased from 24 to 200 nmi. TPE(CO2) and TPE(PM2.5) estimated for large
      container vessels showed benefits for CO(2) (2-26%) and PM(2.5) (4-57%) on
      reducing speeds from 15 to 12 knots, whereas TPE(CO2) and TPE(PM2.5) for small
      and medium container vessels were similar at 15 and 12 knots.

PMID- 22974076
TI  - Giant squamous cell carcinoma as a complication of a chronic enterocutaneous
      fistula: complex parietal reconstruction.
AB  - Treatment of an enterocutaneous fistula is complex and may require
      multidisciplinary management, especially when associated with a neoplastic
      process. Here, we describe the case of a 59-year-old patient with a squamous cell
      carcinoma that had invaded the abdominal wall through a chronic enterocutaneous
      fistula identified 30 years ago. We combined parietectomy with small intestine
      and colon resection and inguinal lymphadenectomy in order to obtain clear
      surgical margins. At the same time, plastic surgery involved the implementation
      of a large bioprosthesis and coverage with a vastus lateralis muscle free flap. 

PMID- 22974077
TI  - Does the organizational model of the maternity health clinic have an influence on
      women's and their partners' experiences? A service evaluation survey in Southwest
      Finland.
AB  - BACKGROUND: In high-income countries, great disparities exist in the
      organizational characteristics of maternity health services. In Finland, primary
      maternity care is provided at communal maternity health clinics (MHC). At these
      MHCs there are public health nurses and general practitioners providing care. The
      structure of services in MHCs varies largely. MHCs are maintained independently
      or merged with other primary health care sectors. A widely used organizational
      model of services is a combined maternity and child health clinic (MHC & CHC)
      where the same public health nurse takes care of the family from pregnancy until
      the child is at school age. The aim of this study was to determine how
      organizational model, MHC independent or combined MHC & CHC, influence on women's
      and their partners' service experiences. METHODS: A comparative, cross-sectional
      service evaluation survey was used. Women (N = 995) and their partners (N = 789)
      were recruited from the MHCs in the area of Turku University Hospital. Four
      months postpartum, the participants were asked to evaluate the content and amount
      of the MHC services via a postal questionnaire. Comparisons were made between the
      clients of the separate MHCs and the MHCs combined to the child health clinics.
      RESULTS: Women who had used the combined MHC & CHCs generally evaluated services
      more positively than women who had used the separate MHCs. MHC's model was
      related to several aspects of the service which were evaluated "good" (the
      content of the service) or "much" (the amount of the service). Significant
      differences accumulated favoring the combined MHC & CHCs' model. Twelve aspects
      of the service were ranked more often as "good" or "much" by the parents who had
      used the combined MHC & CHC, only group activities regarding delivery were
      evaluated better by women who had used the separate MHCs. CONCLUSIONS: Based on
      the women's and partners' experiences an organizational model of the combined MHC
      & CHC where the same nurse will take care of family during pregnancy and after
      birth of the child was preferred. This model also provides greater amount of home
      visits and peer support than the separate MHC.

PMID- 22974078
TI  - Analysis of tiling array expression studies with flexible designs in Bioconductor
      (waveTiling).
AB  - BACKGROUND: Existing statistical methods for tiling array transcriptome data
      either focus on transcript discovery in one biological or experimental condition
      or on the detection of differential expression between two conditions.
      Increasingly often, however, biologists are interested in time-course studies,
      studies with more than two conditions or even multiple-factor studies. As these
      studies are currently analyzed with the traditional microarray analysis
      techniques, they do not exploit the genome-wide nature of tiling array data to
      its full potential. RESULTS: We present an R Bioconductor package, waveTiling,
      which implements a wavelet-based model for analyzing transcriptome data and
      extends it towards more complex experimental designs. With waveTiling the user is
      able to discover (1) group-wise expressed regions, (2) differentially expressed
      regions between any two groups in single-factor studies and in (3) multifactorial
      designs. Moreover, for time-course experiments it is also possible to detect (4)
      linear time effects and (5) a circadian rhythm of transcripts. By considering the
      expression values of the individual tiling probes as a function of genomic
      position, effect regions can be detected regardless of existing annotation. Three
      case studies with different experimental set-ups illustrate the use and the
      flexibility of the model-based transcriptome analysis. CONCLUSIONS: The
      waveTiling package provides the user with a convenient tool for the analysis of
      tiling array trancriptome data for a multitude of experimental set-ups.
      Regardless of the study design, the probe-wise analysis allows for the detection
      of transcriptional effects in both exonic, intronic and intergenic regions,
      without prior consultation of existing annotation.

PMID- 22974079
TI  - The evolution and value of bleeding assessment tools.
AB  - A personal history of excessive mucocutaneous bleeding is a key component in the
      diagnosis of a number of mild bleeding disorders, including von Willebrand
      disease (VWD), platelet function disorders (PFD), and coagulation factor
      deficiencies. However, the evaluation of hemorrhagic symptoms is a well
      recognized challenge for both patients and physicians, because the reporting and
      interpretation of bleeding symptoms is subjective. As a result, bleeding
      assessment tools (BATs) have been developed and studied in a variety of clinical
      settings. This work has been pioneered by a group of Italian researchers, and the
      resultant 'Vicenza Bleeding Questionnaire' stands as the original BAT. In this
      review, we will discuss the modifications of the Vicenza Bleeding Questionnaire
      that have taken place over the years, as well as the validation studies that have
      been published. Other BATs that have been developed and published will be
      reviewed, as will the special situations of assessing pediatric bleeding as well
      as menorrhagia. Lastly, the clinical utility of BATs will be discussed including
      remaining challenges and future directions for the field.

PMID- 22974081
TI  - Decision-making process of family caregivers regarding placement of a cognitively
      impaired elderly relative.
AB  - Grounded theory served to develop a model of the family caregiver decision-making
      process regarding placement of a cognitively impaired elderly relative. Eighteen
      caregivers were interviewed every 6 months over an average 20 months. Results
      show the process is activated when the caregiver or a health care professional
      introduces the possibility of placement. The caregiver's assessment of the pros
      and cons of placement is modulated primarily by interactions with the formal and
      informal social network. Three types of longitudinal trajectory emerged from the
      data suggesting avenues of intervention to support caregivers during this painful
      process.

PMID- 22974080
TI  - Will Mobile Diabetes Education Teams (MDETs) in primary care improve patient care
      processes and health outcomes? Study protocol for a randomized controlled trial.
AB  - BACKGROUND: There is evidence to suggest that delivery of diabetes self
      management support by diabetes educators in primary care may improve patient care
      processes and patient clinical outcomes; however, the evaluation of such a model
      in primary care is nonexistent in Canada. This article describes the design for
      the evaluation of the implementation of Mobile Diabetes Education Teams (MDETs)
      in primary care settings in Canada. METHODS/DESIGN: This study will use a non
      blinded, cluster-randomized controlled trial stepped wedge design to evaluate the
      Mobile Diabetes Education Teams' intervention in improving patient clinical and
      care process outcomes. A total of 1,200 patient charts at participating primary
      care sites will be reviewed for data extraction. Eligible patients will be those
      aged >=18, who have type 2 diabetes and a hemoglobin A1c (HbA1c) of >=8%.
      Clusters (that is, primary care sites) will be randomized to the intervention and
      control group using a block randomization procedure within practice size as the
      blocking factor. A stepped wedge design will be used to sequentially roll out the
      intervention so that all clusters eventually receive the intervention. The time
      at which each cluster begins the intervention is randomized to one of the four
      roll out periods (0, 6, 12, and 18 months). Clusters that are randomized into the
      intervention later will act as the control for those receiving the intervention
      earlier. The primary outcome measure will be the difference in the proportion of
      patients who achieve the recommended HbA1c target of <=7% between intervention
      and control groups. Qualitative work (in-depth interviews with primary care
      physicians, MDET educators and patients; and MDET educators' field notes and
      debriefing sessions) will be undertaken to assess the implementation process and
      effectiveness of the MDET intervention. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01553266.

PMID- 22974082
TI  - Access barriers to and unmet needs for home- and community-based services among
      older Korean Americans.
AB  - This cross-sectional survey study of 146 caregivers of older Korean Americans
      explored access barriers to and unmet needs for home- and community-based
      services (HCBS) programs (respite care, adult day care, personal care, home
      health, housekeeping, and transportation). Most often reported access barriers
      were lack of awareness and care recipient refusal. Predictors of unmet needs
      varied depending on the type of service, but included caregiver gender,
      relationship, education, caregiving duration, Medicaid coverage, English
      proficiency, caregiver self-efficacy, care recipient functional dependency,
      cognitive impairment, and caregiving hours. This study highlighted unmet needs
      for HCBS in Korean American communities, pointing to the pressing need for a
      collaborative effort to develop plans that modify and expand HCBS programs for
      older Korean Americans.

PMID- 22974083
TI  - Home care nurses' experience of job stress and considerations for the work
      environment.
AB  - Home care nurses report increased stress in their jobs due to work environment
      characteristics that impact professional practice. Stressors and characteristics
      of the professional practice environment that moderate nurses' experience of job
      stress were examined in this embedded multiple case study. Real life experiences
      within a complex environment were drawn from interviews and observations with 29
      participants across two home care agencies from one eastern U.S. state. Findings
      suggest that role overload, role conflict, and lack of control can be moderated
      in agencies where there are meaningful opportunities for shared decision making
      and the nurse-patient relationship is supported.

PMID- 22974084
TI  - Patient and provider views on the use of medical services by women with
      intellectual disabilities.
AB  - BACKGROUND: People with intellectual disabilities (ID) receive primary care in
      community-based practices and are encouraged to participate in the physician
      patient relationship. However, the nature of this participation is not known.
      METHODS: Qualitative data were analysed to obtain perspectives from patients and
      providers regarding clinic visits. Patient participants were recruited from
      community organisations, while physician participants were recruited from emails
      and phone calls to local and regional practices and a national and regional list
      serve. Analysis methods derived from grounded theory were used. RESULTS: Twenty
      seven women with ID and 22 family physicians were interviewed. Themes important
      to both groups included time, how the support worker should be used in the
      encounter and the nature of the physician-patient relationship. Patients
      expressed frustration at how little time they spent with their physician, and
      wished that physicians would speak directly to them instead of to their support
      worker. Physicians felt that patients with ID took too much time, and said that
      they preferred communicating with the support worker. The interviews also
      revealed unconscious biases about people with ID. CONCLUSIONS: Patient
      participation is encouraged for people with ID, but is limited because of both
      physician and patient factors. Greater awareness of these factors may improve
      care for patients with ID.

PMID- 22974085
TI  - Electrospun self-standing membrane of hierarchical SiO2@gamma-AlOOH (boehmite)
      core/sheath fibers for water remediation.
AB  - Hierarchical SiO(2)@gamma-AlOOH (Boehmite) core/sheath fibers are fabricated
      based on a combination of electrospinning and hydrothermal reaction. gamma-AlOOH
      (Boehmite) nanoplatelets are uniformly anchored on the surface of SiO(2) fibers,
      which significantly improves the adsorption efficiency of the SiO(2) fiber
      membrane for organic dyes and microorganisms. Compared to conventional
      nanoparticle adsorbents, the self-standing membrane thus prepared is highly
      flexible and easy to handle and retrieve, making it a promising material for
      water treatment. By virtue of electrospinning and a hydrothermal reaction, it
      provides possibilities to fabricate other functional fiber membranes with
      hierarchical structures, which can find potential applications in adsorption,
      catalysis, filtration, and other environmental remediation fields.

PMID- 22974087
TI  - Giant hydatid cyst of the liver with a retroperitoneal growth: a case report.
AB  - INTRODUCTION: Hydatid disease is a helminthic anthropozoonosis with worldwide
      distribution due to the close associations among sheep, dogs, and humans. It can
      occur almost anywhere in the body with a variety of imaging features, which may
      change according to the growth stage, associated complications, and affected
      tissues. A definitive diagnosis requires a combination of imaging, serologic and
      immunologic studies. Ultrasonography, computed tomography and magnetic resonance
      imaging are highly accurate in detecting a hepatic hydatid cyst. However, hepatic
      hydatid cysts in an unusual location and/or of an unusual dimension, with
      atypical imaging findings, may complicate the differential diagnosis. Surgical
      treatment remains the best treatment. CASE PRESENTATION: We describe an unusual
      case of a giant hydatid cyst, with exophytic growth from the right lobe of the
      liver of a 55-year-old Egyptian man. The cyst was strongly adhered to his
      ipsilateral kidney, which was displaced in a downwards and anterior direction,
      close to his abdominal wall, simulating a retroperitoneal origin. This atypical
      growth raised doubts about the most appropriate surgical approach. Magnetic
      resonance imaging easily clarified the origin of the cyst as our patient's liver,
      allowing accurate surgical planning. CONCLUSION: Rarely, hydatid cysts can reach
      an extremely large size without any additional symptoms. Giant cysts need radical
      therapy because they might lead to perforation and anaphylaxis in some patients.
      Magnetic resonance imaging is very useful in the study of hydatid disease because
      of its capacity to allow a large field of view, multiplanar acquisition, and high
      contrast resolution. In some unusual hepatic presentations, magnetic resonance
      imaging can be used to determine the correct anatomical relationships.

PMID- 22974086
TI  - Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference
      clone to improve comparisons of Plasmodium falciparum field isolates.
AB  - BACKGROUND: Apparent emerging artemisinin-resistant Plasmodium falciparum malaria
      in Southeast Asia requires development of practical tools to monitor for
      resistant parasites. Although in vitro anti-malarial susceptibility tests are
      widely used, uncertainties remain regarding interpretation of P. falciparum field
      isolate values. METHODS: Performance parameters of the W2 P. falciparum clone
      (considered artemisinin "sensitive") were evaluated as a reference for the HRP-2
      immediate ex vivo assay. Variability in W2 IC50s was assessed, including intra-
      and inter-assay variability among and between technicians in multiple
      experiments, over five freeze-thaw cycles, over five months of continuous
      culture, and before and after transport of drug-coated plates to remote field
      sites. Nominal drug plate concentrations of artesunate (AS) and
      dihydroartemisinin (DHA) were verified by LC-MS analysis. Plasmodium falciparum
      field isolate IC50s for DHA from subjects in an artemisinin-resistant area in
      Cambodia were compared with W2 susceptibility. RESULTS: Plate drug concentrations
      and day-to-day technical assay performance among technicians were important
      sources of variability for W2 IC50s within and between assays. Freeze-thaw
      cycles, long-term continuous culture, and transport to and from remote sites had
      less influence. Despite variability in W2 susceptibility, the median IC50s for
      DHA for Cambodian field isolates were higher (p <0.0001) than the W2 clone (3.9
      nM), both for subjects with expected (less than 72 hours; 6.3 nM) and prolonged
      (greater or equal to 72 hours; 9.6 nM) parasite clearance times during treatment
      with artesunate monotherapy. CONCLUSION: The W2 reference clone improved the
      interpretability of field isolate susceptibility from the immediate ex vivo HRP-2
      assay from areas of artemisinin resistance. Methods to increase the
      reproducibility of plate coating may improve overall assay interpretability and
      utility.

PMID- 22974088
TI  - Ab initio quantum chemistry for protein structures.
AB  - Structural properties of over 55 small proteins have been determined using both
      density-based and wave-function-based electronic structure methods in order to
      assess the ability of ab initio "force fields" to retain the properties described
      by experimental structures measured with crystallography or nuclear magnetic
      resonance. The efficiency of the GPU-based quantum chemistry algorithms
      implemented in our TeraChem program enables us to carry out systematic
      optimization of ab initio protein structures, which we compare against
      experimental and molecular mechanics force field references. We show that the
      quality of the ab initio optimized structures, as judged by conventional protein
      health metrics, increases with increasing basis set size. On the other hand,
      there is little evidence for a significant improvement of predicted structures
      using density functional theory as compared to Hartree-Fock methods. Although
      occasional pathologies of minimal basis sets are observed, these are easily
      alleviated with even the smallest double-zeta basis sets.

PMID- 22974089
TI  - Sexual desire and hypoactive sexual desire disorder in women. Introduction and
      overview. Standard operating procedure (SOP Part 1).
AB  - INTRODUCTION: Hypoactive sexual desire disorder (HSDD) is defined in Diagnostic
      and Statistical Manual of Mental Disorders Fourth Edition as persistent or
      recurrent deficiency (or absence) of sexual fantasies/thoughts, and/or desire for
      or receptivity to sexual activity, which causes personal distress. As a largely
      subjective experience, sexual desire may or may not be accompanied by externally
      observable changes in sexual behavior. AIM: Describe the models of understanding
      HSDD and the contributing factors to provide the basis for a diagnostic interview
      and guidance for care for healthcare professionals as a standard operating
      procedure method. Review of the literature. RESULTS: There are several models
      which have been developed to describe sexual desire, although there is still no
      universally accepted definition or description of it. The models are generally
      divided into more general two-factor models (e.g., excitation-inhibition,
      appetitive-consummatory) or more specific multifactorial models (in which the
      different components of sexual activity and their interaction are delineated).
      The etiology of the disorder is generally considered as multifactorial.
      Biomedical factors like diseases, drugs, and hormones, and psychological factors
      like life events, sexual biography, affective state, etc., as well as
      interpersonal factors like partner satisfaction, communication, duration of the
      relationship, and sociocultural factors interact with each other and contribute
      to the individual experience of desire or lack or absence of desire. In analogy
      to the multifactorial pathogenesis the therapeutic approach is usually
      multidimensional and includes basic counseling, individual and couple
      psychotherapy, hormonal and psychopharmacological treatment. CONCLUSION: The
      standard operation procedure for HSDD in women must be based on a
      biopsychosocial, multidimensional, and integrative perspective.

PMID- 22974090
TI  - Angiotensin II: role in skeletal muscle atrophy.
AB  - Skeletal muscle, the main protein reservoir in the body, is a tissue that
      exhibits high plasticity when exposed to changes. Muscle proteins can be
      mobilized into free amino acids when skeletal muscle wasting occurs, a process
      called skeletal muscle atrophy. This wasting is an important systemic or local
      manifestation under disuse conditions (e.g., bed rest or immobilization), in
      starvation, in older adults, and in several diseases. The molecular mechanisms
      involved in muscle wasting imply the activation of specific signaling pathways
      which ultimately manage muscle responses to modulate biological events such as
      increases in protein catabolism, oxidative stress, and cell death by apoptosis.
      Many factors have been involved in the generation and maintenance of atrophy in
      skeletal muscle, among them angiotensin II (Ang-II), the main peptide of renin
      angiotensin system (RAS). Together with Ang-II, the angiotensin-converting enzyme
      (ACE) and the Ang-II receptor type 1 (AT-1 receptor) are expressed in skeletal
      muscle, forming an important local axis that can regulate its function. In many
      of the conditions that lead to muscle wasting, there is an impairment of RAS in a
      global or local fashion. At this point, there are several pieces of evidence that
      suggest the participation of Ang-II, ACE, and AT-1 receptor in the generation of
      skeletal muscle atrophy. Interestingly, the Ang-II participation in muscle
      atrophy is strongly ligated to the regulation of hypertrophic activity of factors
      such as insulin-like growth factor 1 (IGF-1). In this article, we reviewed the
      current state of Ang-II and RAS function on skeletal muscle wasting and its
      possible use as a therapeutic target to improve skeletal muscle function under
      atrophic conditions.

PMID- 22974091
TI  - Prognostic value of uric acid in patients with Type 2 diabetes mellitus and
      coronary artery disease.
AB  - Studies investigating the prognostic role of UA (uric acid) in patients with Type
      2 diabetes mellitus have given conflicting findings. We undertook the present
      study to assess the association between UA and outcome in patients with Type 2
      diabetes mellitus and CAD (coronary artery disease). The study included 3705
      patients with diabetes mellitus and angiography-proven CAD. UA was measured
      before coronary angiography. The primary outcome was 1-year all-cause mortality.
      The UA concentration [median (25th-75th quartiles)] was 6.44 mg/dl (5.40-7.70
      mg/dl). There were 264 deaths (7.1%) during follow-up: 45 deaths in patients of
      the first UA quartile, 43 deaths in patients of the second UA quartile, 51 deaths
      in patients of the third UA quartile and 125 deaths in patients of the fourth UA
      quartile {Kaplan-Meier estimates of mortality, 5.1, 4.8, 5.6 and 14.0%
      respectively; unadjusted HR (hazard ratio), 2.81 [95% CI (confidence interval),
      2.21-3.58]; P<0.001 for fourth quartile compared with first-third quartiles
      combined}. In the multivariable analysis, UA predicted all-cause mortality with
      an adjusted HR of 1.29 (95% CI, 1.12-1.48; P<0.001), for each S.D. increase in
      the logarithmic scale of UA level. The inclusion of UA in the multivariable model
      alongside known cardiovascular risk factors and other relevant variables
      increased the discriminatory power of the model regarding prediction of all-cause
      mortality [absolute and relative IDI (integrated discrimination improvement)
      0.034 and 20.5% respectively; P<0.001]. In conclusion, in patients with Type 2
      diabetes mellitus and confirmed CAD, elevated levels of UA predict mortality
      independently of known cardiovascular risk factors.

PMID- 22974092
TI  - Evaluation of predictive markers for patients with advanced colorectal cancer.
AB  - BACKGROUND: To evaluate the predictive and prognostic value of serum and plasma
      tumor markers, in comparison with clinical and biomedical parameters for response
      rate (RR), progression-free survival (PFS) and overall survival (OS) among
      patients with metastatic colorectal cancer (mCRC) treated with combination
      chemotherapy. MATERIAL AND METHODS: One-hundred and six patients with mCRC from
      three centers, part of a multicenter study, received irinotecan with the Nordic
      bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont
      schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA,
      transthyretin and CRP were taken at baseline and after two, four and eight weeks
      of treatment. Tumor marker levels at baseline and longitudinally were compared
      with responses evaluated (CT/MRI) after two and four months of treatment. The
      correlations to RR, PFS and OS were evaluated with regression analyses. RESULTS:
      A significant correlation to OS was seen for baseline levels of all markers. In
      multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided
      independent information. The baseline values of CEA, TPA and TIMP-1 were also
      significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the
      slope gave with the exception of CA19-9 for OS less information about outcomes.
      The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values
      of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an
      interaction between the slope and the baseline value. CONCLUSIONS: Baseline tumor
      markers together with clinical parameters provide prognostic information about
      survival in patients with mCRC. The ability of the individual tumor markers to
      predict treatment response and PFS is limited. Changes in marker levels during
      the first two months of treatment are less informative of outcome.

PMID- 22974093
TI  - Data quality at the Icelandic Cancer Registry: comparability, validity,
      timeliness and completeness.
AB  - INTRODUCTION: The nationwide Icelandic Cancer Registry (ICR) was established in
      1954 and has been extensively used for research from the outset although formal
      quality assessment of the registry database has not previously been undertaken.
      In this paper we report the first formal evaluation of the comparability,
      validity, timeliness and completeness of the ICR. MATERIAL AND METHODS: Data from
      the ICR for the period 1955-2009 (41 994 cancer diagnoses) were used, applying
      established quantitative and semi-quantitative methods. In order to evaluate the
      completeness of the ICR, record linkage was performed between the ICR and the
      population-based Hospital Discharge Registry to identify potential missing cases
      for tumour diagnoses in 2000 and 2001. RESULTS: The registration is in accordance
      with internationally accepted standards. It has high validity, but random
      variation in rates is prominent in this small population. Record linkage with the
      Hospital Discharge Registry revealed that in addition to the 2459 cancers
      registered in 2000-2001, 21 cases were missing, indicating 99.15% completeness.
      Tumours of the central nervous system constituted 71%, and haematological
      malignancies 19% of these missing entries. DISCUSSION: The ICR has high
      completeness, validity and timeliness and is comparable to the cancer registries
      of the other Nordic Countries. As cancer registries have many important roles, it
      is of great importance that their data are at all times as complete and valid as
      possible. Thus the ICR aims to constantly improve and update the data gathering
      process.

PMID- 22974094
TI  - Non-inferiority trials in breast and non-small cell lung cancer: choice of non
      inferiority margins and other statistical aspects.
AB  - BACKGROUND: Determining the non-inferiority margin is an essential step in the
      design and interpretation of non-inferiority trials, and this margin should be
      preferably justified on clinical and statistical grounds. METHODS: After a PubMed
      search for phase III trials in advanced breast cancer (BC) or non-small cell lung
      cancer (NSCLC) published between January 1998 and December 2009 in 11 leading
      journals, non-inferiority trials were selected by manual search of the full
      papers. RESULTS: Twenty-four of 195 trials had a primary non-inferiority
      hypothesis. When the two six-year study periods were compared, there were time
      trends within BC and NSCLC, with most non-inferiority trials in BC reported in
      the first six-year period, and vice-versa for NSCLC. The median sample size was
      larger for non-inferiority than superiority trials (p < 0.01). The choice of a
      non-inferiority margin was reportedly justified in only five cases. Non
      inferiority trials were more likely than superiority trials to yield positive
      results (p < 0.001), as were trials in breast cancer (p = 0.02). CONCLUSIONS: Non
      inferiority margins for cancer trials appear to be chosen mostly on historical
      grounds. Since nearly three-quarters of non-inferiority trials achieve their
      primary objective, the extent to which the choice of margins has influence on
      trial results remains to be determined.

PMID- 22974095
TI  - Doctoral Dissertation: Rajaraman Swaminathan: an evaluation of survival of cancer
      patients based on registry data from low or medium resource countries.

PMID- 22974096
TI  - Burden of stroke in Bangladesh.
AB  - Stroke is the third leading cause of death in Bangladesh. The World Health
      Organization ranks Bangladesh's mortality rate due to stroke as number 84 in the
      world. The reported prevalence of stroke in Bangladesh is 0.3%, although no data
      on stroke incidence have been recorded. Hospital-based studies conducted in past
      decades have indicated that hypertension is the main cause of ischaemic and
      haemorrhagic stroke in Bangladesh. The high number of disability-adjusted life
      years lost due to stroke (485 per 10,000 people) show that stroke severely
      impacts Bangladesh's economy. Although two non-governmental organizations, BRAC
      and the Centre for the Rehabilitation of the Paralysed, are actively involved in
      primary stroke prevention strategies, the Bangladeshi government needs to
      emphasize healthcare development to cope with the increasing population density
      and to reduce stroke occurrence.

PMID- 22974097
TI  - Transparent, conducting Nb:SnO2 for host-guest photoelectrochemistry.
AB  - Many candidate materials for photoelectrochemical water splitting will be better
      employed by decoupling optical absorption from carrier transport. A promising
      strategy is to use multiple thin absorber layers supported on transparent,
      conducting materials; however there are limited such materials that are both pH
      stable and depositable on arbitrary high surface area substrates. Here we present
      the first 3D porous niobium doped tin oxide (NTO) electrodes fabricated by atomic
      layer deposition. After high temperature crystallization the NTO is transparent,
      conductive, and stable over a wide range of pH. The optimized films have high
      electrical conductivity up to 37 S/cm concomitant with a low optical attenuation
      coefficient of 0.99 MUm(-1) at 550 nm. NTO was deposited onto high surface area
      templates that were subsequently coated with hematite Fe(2)O(3) for the
      photoelectrochemical water splitting. This approach enabled near-record water
      splitting photocurrents for hematite electrodes employing a host-guest strategy.

PMID- 22974098
TI  - Reply to Dr Tomita's letter.

PMID- 22974099
TI  - Convergent evolution of modularity in metabolic networks through different
      community structures.
AB  - BACKGROUND: It has been reported that the modularity of metabolic networks of
      bacteria is closely related to the variability of their living habitats. However,
      given the dependency of the modularity score on the community structure, it
      remains unknown whether organisms achieve certain modularity via similar or
      different community structures. RESULTS: In this work, we studied the
      relationship between similarities in modularity scores and similarities in
      community structures of the metabolic networks of 1021 species. Both similarities
      are then compared against the genetic distances. We revisited the association
      between modularity and variability of the microbial living environments and
      extended the analysis to other aspects of their life style such as temperature
      and oxygen requirements. We also tested both topological and biological intuition
      of the community structures identified and investigated the extent of their
      conservation with respect to the taxonomy. CONCLUSIONS: We find that similar
      modularities are realized by different community structures. We find that such
      convergent evolution of modularity is closely associated with the number of
      (distinct) enzymes in the organism's metabolome, a consequence of different life
      styles of the species. We find that the order of modularity is the same as the
      order of the number of the enzymes under the classification based on the
      temperature preference but not on the oxygen requirement. Besides, inspection of
      modularity-based communities reveals that these communities are graph
      theoretically meaningful yet not reflective of specific biological functions.
      From an evolutionary perspective, we find that the community structures are
      conserved only at the level of kingdoms. Our results call for more investigation
      into the interplay between evolution and modularity: how evolution shapes
      modularity, and how modularity affects evolution (mainly in terms of fitness and
      evolvability). Further, our results call for exploring new measures of modularity
      and network communities that better correspond to functional categorizations.

PMID- 22974100
TI  - Feasibility study of an internally cooled bipolar applicator for RF coagulation
      of hepatic tissue: experimental and computational study.
AB  - PURPOSE: To study the capacity of an internally cooled radiofrequency (RF)
      bipolar applicator to create sufficiently deep thermal lesions in hepatic tissue.
      MATERIALS AND METHODS: Three complementary methodologies were employed to check
      the electrical and thermal behaviour of the applicator under test. The
      experimental studies were based on excised bovine (ex vivo study) and porcine
      liver (in vivo study) and the theoretical models were solved by means of the
      finite element method (FEM). RESULTS: Experimental and computational results
      showed good agreement in terms of impedance progress and lesion depth (4 and 4.5
      mm respectively for ex vivo conditions, and ~7 and 9 mm respectively for in vivo
      conditions), although the lesion widths were overestimated by the computer
      simulations. This could have been due to the method used to assess the thermal
      lesions; the experimental lesions were assessed by the white coagulation zone,
      whereas the tissue damage function was used to assess the computational lesions.
      CONCLUSIONS: The experimental results suggest that this applicator could create
      in vivo lesions to a depth of around 7 mm. It was also observed that the thermal
      lesion is mainly confined to the area between both electrodes, which would allow
      lesion width to be controlled by selecting a specific applicator design. The
      comparison between the experimental and computational results suggests that the
      theoretical model could be usefully applied in further studies of the performance
      of this device.

PMID- 22974101
TI  - Redundant functions of phospholipases D1 and D2 in platelet alpha-granule
      release.
AB  - BACKGROUND: Platelet activation and aggregation are crucial for primary
      hemostasis, but can also result in occlusive thrombus formation. Agonist-induced
      platelet activation involves different signaling pathways leading to the
      activation of phospholipases, which produce second messengers. The role of
      phospholipase C (PLC) in platelet activation is well established, but less is
      known about the relevance of phospholipase D (PLD). OBJECTIVE AND METHODS: The
      aim of this study was to determine a potential function of PLD2 in platelet
      physiology. Thus, we investigated the function of PLD2 in platelet signaling and
      thrombus formation, by generating mice lacking PLD2 or both PLD1 and PLD2.
      Adhesion, activation and aggregation of PLD-deficient platelets were analyzed in
      vitro and in vivo. RESULTS: Whereas the absence of PLD2 resulted in reduced PLD
      activity in platelets, it had no detectable effect on the function of the cells
      in vitro and in vivo. However, the combined deficiency of both PLD isoforms
      resulted in defective alpha-granule release and protection in a model of FeCl3 
      induced arteriolar thrombosis, effects that were not observed in mice lacking
      only one PLD isoform. CONCLUSION: These results reveal redundant roles of PLD1
      and PLD2 in platelet alpha-granule secretion, and indicate that this may be
      relevant for pathologic thrombus formation.

PMID- 22974102
TI  - The effects of alcohol abstinence on BDNF, ghrelin, and leptin secretions in
      alcohol-dependent patients with glucose intolerance.
AB  - BACKGROUND: Alcohol use affecting the risk of type 2 diabetes mellitus (T2DM) is
      poorly identified as well as the role of brain-derived neurotrophic factor
      (BDNF), ghrelin, and leptin in alcohol dependence with T2DM. We tested the
      hypothesis that alcohol abstinence affects diabetes-related factors and BDNF,
      ghrelin, and leptin secretions in alcohol-dependent patients with glucose
      intolerance. METHODS: A total of 64 male alcohol-dependent patients were
      classified into normal glucose tolerance (NGT), pre-diabetes mellitus (pre-DM),
      and diabetes mellitus (DM) groups according to a 75-g oral glucose tolerance test
      (OGTT). All participants got alcohol dependence rehabilitation treatment for 30
      days, and then we compared changes in BDNF, ghrelin, and leptin between pre- and
      post-alcohol abstinence. RESULTS: After alcohol abstinence, both pre-DM and DM
      groups had significantly decreased levels of fasting glucose. All 3 groups
      exhibited elevated ghrelin levels and reduced leptin levels, but BDNF levels were
      significantly increased only in the pre-DM group. The pre-DM group had large
      increases in BDNF and ghrelin levels compared with those of the NGT group.
      Moreover, decreases in homeostasis model assessment of insulin resistance (HOMA
      IR), fasting glucose, and leptin levels in the DM group were larger than those in
      the NGT group. CONCLUSIONS: Alcohol abstinence might influence diabetes-related
      factors of alcohol-dependent patients with glucose intolerance. Further, BDNF,
      ghrelin, and leptin differently affect this improvement, depending on the stage
      of DM. In the pre-DM group, elevated BDNF and ghrelin levels are likely to
      influence insulin sensitivity, insulin resistance, and fasting glucose levels.
      Further, reduced leptin levels after abstinence might be related to improved
      glucose kinetics in patients with diabetes.

PMID- 22974103
TI  - Contribution of water-soluble and insoluble components and their
      hydrophobic/hydrophilic subfractions to the reactive oxygen species-generating
      potential of fine ambient aerosols.
AB  - Relative contributions of water- and methanol-soluble compounds and their
      hydrophobic/hydrophilic subfractions to the ROS (reactive oxygen species)
      generating potential of ambient fine aerosols (D(p) < 2.5 MUm) are assessed. ROS
      generating (or oxidative) potential of the particulate matter (PM) was measured
      by the dithiothreitol (DTT) assay. Particles were collected on quartz filters (N
      = 8) at an urban site near central Atlanta during January-February 2012 using a
      PM(2.5) high-volume sampler. Filter punches were extracted separately in both
      water and methanol. Hydrophobic and hydrophilic fractions were then subsequently
      segregated via a C-18 solid phase extraction column. The DTT assay response was
      significantly higher for the methanol extract, and for both extracts a
      substantial fraction of PM oxidative potential was associated with the
      hydrophobic compounds as evident from a substantial attenuation in DTT response
      after passing PM extracts through the C-18 column (64% for water and 83% for
      methanol extract; both median values). The DTT activities of water and methanol
      extracts were correlated with the water-soluble (R = 0.86) and water-insoluble
      organic carbon (R = 0.94) contents of the PM, respectively. Brown carbon (BrC),
      which predominantly represents the hydrophobic organic fraction (referred to as
      humic-like substances, HULIS), was also correlated with DTT activity in both the
      water (R = 0.78) and methanol extracts (R = 0.83). Oxidative potential was not
      correlated with any metals measured in the extracts. These findings suggest that
      the hydrophobic components of both water-soluble and insoluble organic aerosols
      substantially contribute to the oxidative properties of ambient PM. Further
      investigation of these hydrophobic organic compounds could help identify sources
      of a significant fraction of ambient aerosol toxicity.

PMID- 22974105
TI  - Treatment intensity in everyday clinical management of speech sound disorders in
      Hong Kong.
AB  - Much evidence supports the efficacy of different treatment approaches for speech
      sound disorders (SSD) in children. Minimal research in the field has been
      conducted using treatment intensity as a research variable. This study examined
      the current practice of speech-language pathologists (SLPs) in Hong Kong
      regarding the treatment intensity prescribed to children with SSD and potential
      factors that were associated with the intensity. Participants were 102 SLPs
      working in different settings in Hong Kong who completed an online questionnaire.
      SLPs who had a heavier caseload offered significantly less frequent and shorter
      treatment duration to clients with SSD. Public and private settings differed
      significantly in treatment duration. Treatment approaches and clinicians'
      consideration about a client's conditions did not affect treatment intensity.
      SLPs in Hong Kong do not plan treatment duration and frequency in an evidence
      based direction because of their heavy workloads and the dearth of research
      evidence on treatment intensity to guide their clinical practice.

PMID- 22974104
TI  - SDHA loss of function mutations in a subset of young adult wild-type
      gastrointestinal stromal tumors.
AB  - BACKGROUND: A subset of KIT/PDGFRA wild-type gastrointestinal stromal tumors (WT
      GIST) have been associated with alteration of the succinate dehydrogenase (SDH)
      complex II function. A recent report identified four non-syndromic, KIT/PDGFRA WT
      GIST harboring compound heterozygous or homozygous mutations in SDHA encoding the
      main subunit of the SDH complex II. METHODS: Next generation sequencing was
      applied on five pediatric and one young adult WT GIST, by whole exome capture and
      SOLiD 3-plus system sequencing. The putative mutations were first confirmed by
      Sanger sequencing and then screened on a larger panel of 11 pediatric and young
      adult WT GIST, including 5 in the context of Carney triad. RESULTS: A germline
      p.Arg31X nonsense SDHA mutation was identified in one of the six cases tested by
      SOLiD platform. An additional p.D38V missense mutation in SDHA exon 2 was
      identified by Sanger sequencing in the extended KIT/PDGFRA WT GIST patients
      cohort. Western blotting showed loss of SDHA expression in the two cases
      harboring SDHA mutations, while expression being retained in the other WT GIST
      tumors. Results were further confirmed by immunohistochemistry for both SDHA and
      SDHB, which showed a concurrent loss of expression of both proteins in SDHA
      mutant lesions, while the remaining WT tumors showed only loss of SDHB
      expression. CONCLUSIONS: Germline and/or somatic aberrations of SDHA occur in a
      small subset of KIT/PDGFRA WT GISTs, outside the Carney's triad and are
      associated with loss of both SDHA and SDHB protein expression. Mutations of the
      SDH complex II are more particularly associated with KIT/PDGFRA WT GIST occurring
      in young adults. Although pediatric GIST consistently display alterations of SDHB
      protein expression, further molecular studies are needed to identify the crucial
      genes involved in their tumorigenesis.

PMID- 22974106
TI  - Characterizing optimal intervention intensity: the relationship between dosage
      and effect size in interventions for children with developmental speech and
      language difficulties.
AB  - Although Warren, Fey and Yoder (2007) have described the key components of
      "dosage", one needs to go beyond description if one is to understand "optimal"
      dosage, specifically one needs to relate the characteristics of the intervention
      to the size of the intervention effect. This study examines the association
      between dose, intensity, and effect size in 20 randomized controlled studies
      taken from a few systematic reviews focusing on interventions aiming to
      ameliorate vocabulary, phonology, and syntax. Reporting of dosage characteristics
      is an important issue. Our analysis shows that "teaching episodes" and "dose
      form" are rarely reported in the included studies. The other dosage
      characteristics are present but not always reported in a transparent fashion.
      Session length and cumulative intervention intensity is lower for phonology
      interventions than it is for vocabulary intervention. Dosage, however defined, is
      not directly associated with outcome, although the level of association varies
      across the three interventions, for example appearing stronger for vocabulary and
      phonology than syntax. Taking the three interventions together the dosage
      components are related to the intervention effects size, but the sample is small
      and the association is not statistically significant. This study concludes that,
      while the framework suggested by Baker (2012) and adapted from Warren et al.
      (2007) is useful but without reference to the effect size of a study, it can only
      ever tell half the story. One needs to be able to relate dosage to outcome,
      asking questions about the relationship between the different dosage
      characteristics and the intervention effect size. Given the available data, it is
      not, at this stage, possible to make recommendations about optimal dosage.

PMID- 22974107
TI  - Optimal intervention intensity in speech-language pathology: discoveries,
      challenges, and unchartered territories.
AB  - This article is the final response in a scientific forum on the optimal intensity
      of intervention in speech-language pathology. It is a reflection on the state of
      knowledge offered by the 13 commentaries in this issue, addressing the areas of
      early communication and language impairment, speech sound disorders in children,
      emergent literacy, reading, aphasia, dysphagia, stuttering, motor speech
      disorders, voice disorders, and traumatic brain injury. Although more intense
      intervention can lead to better outcomes, the relationship between intensity and
      outcome is not always linear. More is not always better. Non-intense and intense
      schedules can yield similar outcomes. Intensity can also reach a point of
      diminishing return. The insights offered by the authors illustrate the challenges
      involved in studying this complex issue. To establish the optimal intensity of
      interventions in speech-language pathology our field needs to: identify active
      ingredients of interventions; better understand how principles of motor learning
      and neural plasticity facilitate learning; appreciate the contribution of
      individuals characteristics, values, and preferences; discover the effect of
      specific combinations of intensity (including dose, dose form, dose frequency,
      session duration, and total intervention duration) on treatment outcomes, and
      find practical solutions when disparities exist between research recommendations
      and workplace limitations.

PMID- 22974109
TI  - Zwitterionic polyurethane hydrogels derived from carboxybetaine-functionalized
      diols.
AB  - The synthesis of novel zwitterionic polyurethane hydrogels with tunable water
      uptake via the polymerization of protected carboxybetaine-functionalized diols
      with polyisocyanate oligomers is presented. Post-polymerization hydrolysis of a
      diol-segment side chain establishes zwitterionic carboxybetaine functionalities
      that facilitate water uptake via the enhanced hydration capacities surrounding
      the opposing charges of the diol component. Tunable hydration of these materials,
      ranging from 24 to 250% solution uptake (based on the dry polymer weight), is
      achieved by controlling the structural characteristics of the diol precursor,
      such as ammonium/carboxylate spacing and ethyl ester hydrolysis conditions (i.e.,
      exposure time to an aqueous base).

PMID- 22974108
TI  - Brief intervention to prevent hazardous drinking in young people aged 14-15 in a
      high school setting (SIPS JR-HIGH): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Whilst the overall proportion of young people drinking alcohol in the
      United Kingdom has decreased in recent years, those who do drink appear to drink
      a larger amount, and more frequently. Early and heavy drinking by younger
      adolescents is a significant public health problem linked to intellectual
      impairment, increased risk of injuries, mental health issues, unprotected or
      regretted sexual experience, violence, and sometimes accidental death, which
      leads to high social and economic costs. This feasibility pilot trial aims to
      explore the feasibility of delivering brief alcohol intervention in a school
      setting with adolescents aged 14 and 15 and to examine the acceptability of study
      measures to school staff, young people and parents. METHODS AND DESIGN: Seven
      schools across one geographical area in the North East of England will be
      recruited. Schools will be randomly allocated to one of three conditions:
      provision of an advice leaflet (control condition, n = 2 schools); a 30-minute
      brief interactive session, which combines structured advice and motivational
      interviewing techniques delivered by the school learning mentor (level 1
      condition, n = 2 schools); and a 60-minute session involving family members
      delivered by the school learning mentor (level 2 condition, n = 3 schools).
      Participants will be year 10 school pupils (aged 14 and 15) who screen positively
      on a single alcohol screening question and who consent to take part in the trial.
      Year 10 pupils in all seven schools will be followed up at 6 and 12 months.
      Secondary outcome measures include the ten-question Alcohol-Use Disorders
      Identification Test. The EQ-5D-Y and a modified short service use questionnaire
      will inform the health and social resource costs for any future economic
      evaluation.Young people recruited into the trial will also complete a 28-day
      timeline follow back questionnaire at 12-month follow-up. A qualitative
      evaluation (with young people, school staff, learning mentors, and parents) will
      examine facilitators and barriers to the use of screening and brief intervention
      approaches in the school setting in this age group. TRIAL REGISTRATION: Trial
      reference number ISRCTN07073105.

PMID- 22974110
TI  - Ageing with an intellectual disability: the impact of personal resources on well
      being.
AB  - BACKGROUND: The population of ageing people with mild and moderate intellectual
      disabilities (ID) is growing rapidly. This study examines how personal resources
      (physical health, mental health and social networks) impact the well-being of
      ageing people with ID. METHODS: Longitudinal survey data on 667 people with a
      mild or moderate ID were acquired via interviews in 2006 and 2010. Indicators of
      personal resources (physical health, mental health and social networks) were
      assessed, as were indicators of well-being (satisfaction with life, happiness and
      loneliness). Additionally, data on background characteristics and autonomy were
      gathered. RESULTS: The results show that age is positively related to decreased
      mobility and auditory disabilities and negatively related to independent living,
      autonomy in how one spends one's leisure time and autonomy in decision-making.
      Longitudinal analyses demonstrated that, with the exception of health that
      deteriorated, and social satisfaction that improved, almost all variables
      remained stable over the 4-year period. Further, good physical health in 2006
      predicted happiness in 2010. CONCLUSION: Despite the fact that age is associated
      with poorer physical and mental health and a smaller social network, this study
      showed that older people with ID have relatively high levels of well-being.
      Findings are discussed in the light of coping with ageing and impact of life
      events.

PMID- 22974111
TI  - Catalytic mechanism of porphobilinogen synthase: the chemical step revisited by
      QM/MM calculations.
AB  - Porphobilinogen synthase (PBGS) catalyzes the asymmetric condensation and
      cyclization of two 5-aminolevulinic acid (5-ALA) substrate molecules to give
      porphobilinogen (PBG). The chemical step of PBGS is herein revisited using QM/MM
      (ONIOM) calculations. Two different protonation states and several different
      mechanisms are considered. Previous mechanisms based on DFT-only calculations are
      shown unlikely to occur. According to these new calculations, the deprotonation
      step rather than ring closure is rate-limiting. Both the C-C bond formation first
      mechanism and the C-N bond formation first mechanism are possible, depending on
      how the A-site ALA binds to the enzyme. We furthermore propose that future work
      should focus on the substrate binding step rather than the enzymatic mechanism.

PMID- 22974112
TI  - Female sexual arousal disorders.
AB  - INTRODUCTION: Definitions and terminology for female sexual arousal disorder
      (FSAD) are currently being debated. While some authors have suggested that FSAD
      is more a subjective response rather than a genital response, others have
      suggested that desire and arousal disorders should be combined in one entity.
      Persistent genital arousal disorder (PGAD) is a new entity which is suggested to
      be defined as Restless Genital Syndrome. Aims.  The aims of this brief review are
      to give definitions of the different types of FSAD, describe their aetiology,
      prevalence and comorbidity with somatic and psychological disorders, as well as
      to discuss different medical and psychological assessment and treatment
      modalities. METHODS: The experts of the International Society for Sexual
      Medicine's Standard Committee convened to provide a survey using relevant
      databases, journal articles, and own clinical experience. RESULTS: Female Arousal
      Disorders have been defined in several ways with focus on the genital or
      subjective response or a combination of both. The prevalence varies and increases
      with increasing age, especially at the time of menopause, while distress
      decreases with age. Arousal disorders are often comorbid with other sexual
      problems and are of biopsychosocial etiology. In the assessment, a thorough
      sexological history as well as medical and gynecological history and examination
      are recommended. Treatment should be based on of the symptoms, clinical findings
      and, if possibly, on underlying etiology. CONCLUSION: Recommendations are given
      for assessment and treatment of FSAD and PGAD.

PMID- 22974113
TI  - Echocardiographic alterations in a child with cow's milk allergy: a case report.
AB  - INTRODUCTION: Cow's milk allergy is the most frequent food allergy in Europe and
      western countries and shows a wide spectrum of clinical features, including
      atopic dermatitis and gastrointestinal disease. To the best of our knowledge,
      this report is the first to describe Kawasaki disease-like clinical features and
      echocardiographic alterations which resolved after a cow's milk-free diet. CASE
      PRESENTATION: We report a case of a 9-month-old Caucasian girl with atopic
      dermatitis who developed clinical features commonly present in Kawasaki disease
      (erythematous skin rash, non-exudative conjunctivitis, fissured lips and neck
      lymph nodes), together with mild echocardiographic alterations (perivascular
      brightness, pericardial effusion) in the absence of fever. These features
      resolved within 2 weeks after the beginning of a cow's milk-free diet.
      CONCLUSION: Kawasaki disease has recently been considered a possible risk factor
      for subsequent allergic disease secondary to immune dysfunction. This case report
      suggests that the immune-related alterations which are commonly present in
      allergic patients could be similar to the antigen-related immune response in
      Kawasaki disease and thus could lead to similar clinical features.

PMID- 22974114
TI  - Hypoglycaemia: exercise for the brain?
AB  - Low blood sugar, or hypoglycaemia, is detected by specialised sugar sensing
      neurones in the brain. However, the detection of hypoglycaemia is blunted after
      repeated hypoglycaemia and this is a result of adaptive mechanisms kicking in
      within the brain; mechanisms that resemble the 'training effect' in muscle. These
      adaptations most likely not only increase the tolerance of the brain to stress,
      but also perturb the detection of hypoglycaemia, further increasing the
      likelihood of hypoglycaemia.

PMID- 22974115
TI  - Assessment of desiccants and their instructions for use in rapid diagnostic
      tests.
AB  - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are protected from humidity
      caused degradation by a desiccant added to the device packaging. The present
      study assessed malaria RDT products for the availability, type and design of
      desiccants and their information supplied in the instructions for use (IFU).
      METHODS: Criteria were based on recommendations of the World Health Organization
      (WHO), the European Community (CE) and own observations. Silica gel sachets were
      defined as self-indicating (all beads coated with a humidity indicator that
      changes colour upon saturation), partial-indicating (part of beads coated) and
      non-indicating (none of the beads coated). Indicating silica gel sachets were
      individually assessed for humidity saturation and (in case of partial-indicating
      silica gels) for the presence of indicating beads. RESULTS: Fifty malaria RDT
      products from 25 manufacturers were assessed, 14 (28%) products were listed by
      the "Global Fund Quality Assurance Policy" and 31 (62%) were CE-marked. All but
      one product contained a desiccant, mostly (47/50, 94%) silica gel. Twenty (40%)
      RDT products (one with no desiccant and 19 with non-indicating desiccant) did not
      meet the WHO guidelines recommending indicating desiccant. All RDT products with
      self- or partial-indicating silica gel (n = 22 and 8 respectively) contained the
      toxic cobalt dichloride as humidity indicator. Colour change indicating humidity
      saturation was observed for 8/16 RDT products, at a median incidence of 0.8%
      (range 0.05%-4.6%) of sachets inspected. In all RDTs with partial-indicating
      silica gel, sachets with no colour indicating beads were found (median proportion
      13.5% (0.6%-17.8%) per product) and additional light was needed to assess the
      humidity colour. Less than half (14/30, 47%) IFUs of RDT products with indicating
      desiccants mentioned to check the humidity saturation before using the test.
      Information on properties, safety hazards and disposal of the desiccant was not
      included in any of the IFUs. There were no differences between Global Fund-listed
      and CE marked RDT products compared to those which were not. Similar findings
      were noted for a panel of 11 HIV RDTs that was assessed with the same checklist
      as the malaria RDTs. CONCLUSION: RDTs showed shortcomings in desiccant type and
      information supplied in the IFU.

PMID- 22974116
TI  - Synthesis and evaluation of novel 18F labeled 2-pyridinylbenzoxazole and 2
      pyridinylbenzothiazole derivatives as ligands for positron emission tomography
      (PET) imaging of beta-amyloid plaques.
AB  - A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2
      pyridinylbenzothiazole derivatives were synthesized and evaluated as novel beta
      amyloid (Abeta) imaging probes for PET. They displayed binding affinities for
      Abeta(1-42) aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high
      affinity were selected for (18)F labeling. In vitro autoradiography results
      confirmed the high affinity of these radiotracers. In vivo biodistribution
      experiments in normal mice indicated that the radiotracers with a short FPEG
      chain (n = 1) displayed high initial uptake into and rapid washout from the
      brain. One of the 2-pyridinylbenzoxazole derivatives, [(18)F]-5-(5-(2
      fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([(18)F]32) (K(i) = 8.0
      +/- 3.2 nM) displayed a brain(2min)/brain(60min) ratio of 4.66, which is highly
      desirable for Abeta imaging agents. Target specific binding of [(18)F]32 to Abeta
      plaques was validated by ex vivo autoradiographic experiment with transgenic
      model mouse. Overall, [(18)F]32 is a promising Abeta imaging agent for PET and
      merits further evaluation in human subjects.

PMID- 22974117
TI  - Aggressive glabellar angiomyxoma with orbital extension.
AB  - A 62-year-old male presented with a large non-tender mass in the glabella,
      extending into the right orbit that had been steadily growing for 6 months.
      Imaging revealed a 2.5 x 1.8 cm cystic mass with extension into the right
      anterior orbit. Biopsy with microscopic examination revealed a predominantly
      myxoid stroma containing spindle-shaped cells with bipolar cigar-shaped nuclei
      and small caliber capillary-type vascular proliferations. These findings are
      consistent with an angiomyxoma. Although angiomyxomas typically present in the
      pelvic region or peritoneum in female patients, there have been rare examples of
      angiomyxomas with orbital involvement.

PMID- 22974118
TI  - Demographics, socio-economic characteristics, and risk factor prevalence in
      patients with non-cardioembolic ischaemic stroke in low- and middle-income
      countries: the OPTIC registry.
AB  - BACKGROUND: There is a paucity of data on patients with stroke/transient
      ischaemic attack in low- and middle-income countries. We sought to describe the
      characteristics and management of patients with an ischaemic stroke and recent
      transient ischaemic attack or minor ischaemic strokes in low- or middle-income
      countries. METHODS: The Outcomes in Patients with TIA and Cerebrovascular disease
      registry is an international, prospective study. Patients >= 45 years who
      required secondary prevention of stroke (either following an acute transient
      ischaemic attack or minor ischaemic strokes (National Institutes of Health Stroke
      Scale <4) of <24 h duration, or recent (<6 months), stable, first-ever, non
      disabling ischaemic stroke) were enrolled in 17 countries in Latin America, the
      Middle East, and Africa. The main measures of interest were risk factors,
      comorbidities, and socio-economic variables. RESULTS: Between January 2007 and
      December 2008, 3635 patients were enrolled in Latin America (n = 1543), the
      Middle East (n = 1041), North Africa (n = 834), and South Africa (n = 217). Of
      these, 63% had a stable, first-ever ischaemic stroke (median delay from symptom
      onset to inclusion, 25 days interquartile range, 7-77); 37% had an acute
      transient ischaemic attack or minor ischaemic stroke (median delay, two-days;
      interquartile range, 0-6). Prevalence of diabetes was 46% in the Middle East, 29%
      in Latin America, 35% in South Africa, and 38% in North Africa; 72% had abdominal
      obesity (range, 65-78%; adjusted P < 0.001); prevalence of metabolic syndrome was
      78% (range, 72-84%, P < 0.001). Abnormal ankle brachial index (<0.9) was present
      in 22%, peripheral artery disease in 7.6%, and coronary artery disease in 13%.
      Overall, 24% of patients had no health insurance and 27% had a low educational
      level. INTERPRETATION: In this study, patients in low- and middle-income
      countries had a high burden of modifiable risk factors. High rates of low
      educational level and lack of health insurance in certain regions are potential
      obstacles to risk factor control. FUNDING: The Outcomes in Patients with TIA and
      Cerebrovascular disease registry is supported by Sanofi-Aventis, Paris, France.

PMID- 22974119
TI  - Center for fetal monkey gene transfer for heart, lung, and blood diseases: an
      NHLBI resource for the gene therapy community.
AB  - The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for
      Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct
      gene transfer studies in monkeys to evaluate safety and efficiency; and to
      provide NHLBI-supported investigators with expertise, resources, and services to
      actively pursue gene transfer approaches in monkeys in their research programs.
      NHLBI-supported projects span investigators throughout the United States and have
      addressed novel approaches to gene delivery; "proof-of-principle"; assessed
      whether findings in small-animal models could be demonstrated in a primate
      species; or were conducted to enable new grant or IND submissions. The Center for
      Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids
      the gene therapy community in addressing regulatory barriers, and serves as an
      effective vehicle for advancing the field.

PMID- 22974121
TI  - Early onset of drinking and risk of heavy drinking in young adulthood--a 13-year
      prospective study.
AB  - BACKGROUND: Prevention programs often aim at preventing early onset of drinking
      (EOD) on the grounds that this may curb heavy drinking in adulthood. While many
      studies have shown an association between EOD and adult alcohol use disorders,
      these findings could be inflated by retrospective reports or insufficient control
      for confounders. This study examined the association between EOD behavior
      assessed in early adolescence and heavy drinking in adulthood, controlling for
      deviant behavior and parental heavy drinking. METHODS: Data were collected
      prospectively over a 13-year period from 1,311 Norwegian school students. At t1
      (ages 13 to 14 years), onset of drinking behavior (any drinking and heavy
      episodic drinking), conduct problems (CP), other problem behaviors, and parental
      heavy drinking were assessed. At t2 (ages 26 to 27 years), heavy drinking
      behavior was assessed in terms of heavy episodic drinking frequency and AUDIT
      score. RESULTS: EOD behavior was associated with CP, other problem behaviors, and
      parental heavy drinking in early adolescence. A higher risk of heavy drinking in
      adulthood was found among those with EOD behavior, yet after control for CP, this
      association became small and statistically nonsignificant. Among low-risk
      individuals (i.e., those with no CP at t1), there was no association between EOD
      behavior and heavy drinking in adulthood, while there was a significant
      association among those with CP. CONCLUSIONS: EOD behavior appears not per se
      responsible for heavy drinking in adulthood unless being part of a broader array
      of problem behaviors.

PMID- 22974120
TI  - De novo assembly of highly diverse viral populations.
AB  - BACKGROUND: Extensive genetic diversity in viral populations within infected
      hosts and the divergence of variants from existing reference genomes impede the
      analysis of deep viral sequencing data. A de novo population consensus assembly
      is valuable both as a single linear representation of the population and as a
      backbone on which intra-host variants can be accurately mapped. The availability
      of consensus assemblies and robustly mapped variants are crucial to the genetic
      study of viral disease progression, transmission dynamics, and viral evolution.
      Existing de novo assembly techniques fail to robustly assemble ultra-deep
      sequence data from genetically heterogeneous populations such as viruses into
      full-length genomes due to the presence of extensive genetic variability,
      contaminants, and variable sequence coverage. RESULTS: We present VICUNA, a de
      novo assembly algorithm suitable for generating consensus assemblies from
      genetically heterogeneous populations. We demonstrate its effectiveness on
      Dengue, Human Immunodeficiency and West Nile viral populations, representing a
      range of intra-host diversity. Compared to state-of-the-art assemblers designed
      for haploid or diploid systems, VICUNA recovers full-length consensus and
      captures insertion/deletion polymorphisms in diverse samples. Final assemblies
      maintain a high base calling accuracy. VICUNA program is publicly available at:
      http://www.broadinstitute.org/scientific-community/science/projects/viral
      genomics/ viral-genomics-analysis-software. CONCLUSIONS: We developed VICUNA, a
      publicly available software tool, that enables consensus assembly of ultra-deep
      sequence derived from diverse viral populations. While VICUNA was developed for
      the analysis of viral populations, its application to other heterogeneous
      sequence data sets such as metagenomic or tumor cell population samples may prove
      beneficial in these fields of research.

PMID- 22974122
TI  - Regulation of fibrinolysis by C-terminal lysines operates through plasminogen and
      plasmin but not tissue-type plasminogen activator.
AB  - BACKGROUND: Binding of tissue-type plasminogen (Pgn) activator (t-PA) and Pgn to
      fibrin regulates plasmin generation, but there is no consistent, quantitative
      understanding of the individual contribution of t-PA finger and kringle 2 domains
      to the regulation of fibrinolysis. Kringle domains bind to lysines in fibrin, and
      this interaction can be studied by competition with lysine analogs and removal of
      C-terminal lysines by carboxypeptidase B (CPB). METHODS: High-throughput, precise
      clot lysis assays incorporating the lysine analog tranexamic acid (TA) or CPB and
      genetically engineered variants of t-PA were performed. In particular, wild-type
      (WT) t-PA (F-G-K1-K2-P) and a domain-switched variant K1K1t-PA (F-G-K1-K1-P) that
      lacks kringle 2 but retains normal t-PA structure were compared to probe the
      importance of fibrin lysine binding by t-PA kringle 2. RESULTS: WT t-PA showed
      higher rates of fibrinolysis than K1K1t-PA, but the inhibitory effects of TA or
      CPB were very similar for WT t-PA and the variant t-PA (< 10% difference).
      Urokinase plasminogen activator (u-PA)-catalyzed fibrinolysis was also inhibited
      by TA, even though Pgn activation could be stimulated. Fibrin treated with factor
      XIIIa (FXIIIa) generates crosslinked degradation products, but these did not
      affect the results obtained with WT t-PA and K1K1t-PA. CONCLUSIONS: t-PA kringle
      2 has a minor role in the initial interaction of t-PA and fibrin, but stimulation
      of fibrinolysis by C-terminal lysines (or inhibition by carboxypeptidases or TA)
      operates through Pgn and plasmin binding, not through t-PA. This is also true
      when fibrin is crosslinked by treatment with FXIIIa.

PMID- 22974123
TI  - Indium-catalyzed reductive bromination of carboxylic acids leading to alkyl
      bromides.
AB  - The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane
      (Me(3)SiBr) with a catalytic amount of indium bromide (InBr(3)) undertook direct
      bromination of carboxylic acids, which produced the corresponding alkyl bromides
      in good to excellent yields. The reducing system was tolerant to several
      functional groups.

PMID- 22974124
TI  - Genome-wide transcription responses to synchrotron microbeam radiotherapy.
AB  - The majority of cancer patients achieve benefit from radiotherapy. A significant
      limitation of radiotherapy is its relatively low therapeutic index, defined as
      the maximum radiation dose that causes acceptable normal tissue damage to the
      minimum dose required to achieve tumor control. Recently, a new radiotherapy
      modality using synchrotron-generated X-ray microbeam radiotherapy has been
      demonstrated in animal models to ablate tumors with concurrent sparing of normal
      tissue. Very little work has been undertaken into the cellular and molecular
      mechanisms that differentiate microbeam radiotherapy from broad beam. The purpose
      of this study was to investigate and compare the whole genome transcriptional
      response of in vivo microbeam radiotherapy versus broad beam irradiated tumors.
      We hypothesized that gene expression changes after microbeam radiotherapy are
      different from those seen after broad beam. We found that in EMT6.5 tumors at 4
      48 h postirradiation, microbeam radiotherapy differentially regulates a number of
      genes, including major histocompatibility complex (MHC) class II antigen gene
      family members, and other immunity-related genes including Ciita, Ifng, Cxcl1,
      Cxcl9, Indo and Ubd when compared to broad beam. Our findings demonstrate
      molecular differences in the tumor response to microbeam versus broad beam
      irradiation and these differences provide insight into the underlying mechanisms
      of microbeam radiotherapy and broad beam.

PMID- 22974125
TI  - Numerical simulation and comparative analysis of flow field in axial blood pumps.
AB  - The objective study was to estimate the rheological properties and physiological
      compatibility of the blood pump by simulating the internal flow field of the
      blood pump. In this study we use computational fluid dynamics method to simulate
      and analyse two models of axial blood pumps with a three-blade diffuser and a six
      blade diffuser, named pump I and pump II, respectively, and to compare the flow
      patterns of these two kinds of blood pumps while both of them satisfy the
      conditions of the normal human blood differential pressure and blood flow.
      Results indicate that (i) the high shear force occurs between the diffuser and
      the rotor in which the crucial place leads to haemolysis and (ii) under the
      condition of 100 mmHg pressure head and 5 l/min flow rate, the difference between
      the two kinds of blood pumps, as far as the haemolytic performance is concerned,
      is notable. The haemolysis index of the two pumps is 0.32% and 0.2%. In
      conclusion, the performance of the blood pump is influenced by the diffusers'
      blade number. Pump II performed better than pump I, which can be the basic model
      for blood pump option. 

PMID- 22974126
TI  - 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and its hydroxylated metabolites are
      enantiomerically enriched in female mice.
AB  - Epidemiological and laboratory studies link polychlorinated biphenyls and their
      metabolites to adverse neurodevelopmental outcomes. Several neurotoxic PCB
      congeners are chiral and undergo enantiomeric enrichment in mammalian species,
      which may modulate PCB developmental neurotoxicity. This study measures levels
      and enantiomeric enrichment of PCB 95 and its hydroxylated metabolites (OH-PCBs)
      in adult female C57Bl/6 mice following subchronic exposure to racemic PCB 95.
      Tissue levels of PCB 95 and OH-PCBs increased with increasing dose. Dose
      dependent enantiomeric enrichment of PCB 95 was observed in brain and other
      tissues. OH-PCBs also displayed enantiomeric enrichment in blood and liver, but
      were not detected in adipose and brain. In light of data suggesting
      enantioselective effects of chiral PCBs on molecular targets linked to PCB
      developmental neurotoxicity, our observations highlight the importance of
      accounting for PCB and OH-PCB enantiomeric enrichment in the assessment of PCB
      developmental neurotoxicity.

PMID- 22974128
TI  - Novel deletion mutation (c.3717del5) in COL7A1 in a patient with recessive
      dystrophic epidermolysis bullosa.

PMID- 22974127
TI  - Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in
      mediating prostate cancer cell apoptosis.
AB  - BACKGROUND: Recent studies suggest the potential benefits of statins as anti
      cancer agents. Mechanisms by which statins induce apoptosis in cancer cells are
      not clear. We previously showed that simvastatin inhibit prostate cancer cell
      functions and tumor growth. Molecular mechanisms by which simvastatin induce
      apoptosis in prostate cancer cells is not completely understood. METHODS: Effect
      of simvastatin on PC3 cell apoptosis was compared with docetaxel using apoptosis,
      TUNEL and trypan blue viability assays. Protein expression of major candidates of
      the intrinsic pathway downstream of simvastatin-mediated Akt inactivation was
      analyzed. Gene arrays and western analysis of PC3 cells and tumor lysates were
      performed to identify the candidate genes mediating extrinsic apoptosis pathway
      by simvastatin. RESULTS: Data indicated that simvastatin inhibited intrinsic cell
      survival pathway in PC3 cells by enhancing phosphorylation of Bad, reducing the
      protein expression of Bcl-2, Bcl-xL and cleaved caspases 9/3. Over-expression of
      PC3 cells with Bcl-2 or DN-caspase 9 did not rescue the simvastatin-induced
      apoptosis. Simvastatin treatment resulted in increased mRNA and protein
      expression of molecules such as TNF, Fas-L, Traf1 and cleaved caspase 8, major
      mediators of intrinsic apoptosis pathway and reduced protein levels of pro
      survival genes Lhx4 and Nme5. CONCLUSIONS: Our study provides the first report
      that simvastatin simultaneously modulates intrinsic and extrinsic pathways in the
      regulation of prostate cancer cell apoptosis in vitro and in vivo, and render
      reasonable optimism that statins could become an attractive anti-cancer agent.

PMID- 22974129
TI  - Impact of different exercise training modalities on the coronary collateral
      circulation and plaque composition in patients with significant coronary artery
      disease (EXCITE trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Exercise training (ET) in addition to optimal medical therapy (OMT)
      in patients with stable coronary artery disease (CAD) has been demonstrated to be
      superior to percutaneous coronary interventions (PCI) with respect to the
      composite endpoint of death, myocardial infarction, stroke, revascularization and
      hospitalization due to worsening of angina. One mechanism leading to this
      superiority discussed in the literature is the increase in coronary collateral
      blood flow due to ET. Until now, data demonstrating the positive effect of ET on
      the collateral blood flow and the functional capacity of the coronary collateral
      circulation are still lacking. METHODS/DESIGN: The EXCITE trial is a three-armed
      randomized, prospective, single-center, open-label, controlled study enrolling 60
      patients with stable CAD and at least one significant coronary stenosis
      (fractional flow reserve <=0.75). The study is designed to compare the influence
      and efficacy of two different 4-week ET programs [high-intensity interval
      trainings (IT) versus moderate-intensity exercise training (MT) in addition to
      OMT] versus OMT only on collateral blood flow (CBF). The primary efficacy
      endpoint is the change of the CBF of the target vessel after 4 weeks as assessed
      by coronary catheterization with a pressure wire during interruption of the
      antegrade flow of the target vessel by balloon occlusion. Secondary endpoints
      include the change in plaque composition as assessed by intravascular ultrasound
      (IVUS) after 4 weeks, myocardial perfusion as analyzed in MRI after 4 weeks and
      12 months, peak oxygen uptake (V02 peak), change in endothelial function and
      biomarkers after 4 weeks, 3, 6 and 12 months. The safety endpoint addresses major
      adverse cardiovascular events (death from cardiovascular cause, myocardial
      infarction, stroke, TIA, target vessel revascularization or hospitalization)
      after 12 months. DISCUSSION: The trial investigates whether ET for 4 weeks
      increases the CBF in patients with significant CAD compared to a sedentary
      control group. It also examines the impact of two intensities of ET on the CBF as
      well as the histological plaque composition. The trial started recruitment in
      June 2009 and will complete recruitment until June 2012. First results are
      expected in December 2012 (4-week follow-up), final results (12-month long-term
      secondary endpoint) in December 2013. TRIAL REGISTRATION: Clinical trial
      registration information-URL: http://www.clinicaltrials.gov.Unique identifier:
      NCT01209637.

PMID- 22974130
TI  - Therapy service use among individuals with fragile X syndrome: findings from a US
      parent survey.
AB  - BACKGROUND: Fragile X syndrome (FXS) is known to be associated with a range of
      developmental challenges, yet the occurrence and intensity of therapy services
      along with associated factors have not been determined. METHOD: In a US national
      survey, caregivers provided information regarding the therapy services received
      by their sons (n = 1013) and daughters (n = 283) with FXS (from birth to 63
      years; mean = 15.6 years, SD = 10.6). Caregivers reported (1) type, (2) amount,
      (3) location, and (4) overall satisfaction with services. Associations with other
      child variables and family income were also examined. RESULTS: Key findings
      included that 72% of males and 47% of females were currently receiving at least
      one type of therapy service; the most common services for both males and females
      were speech-language therapy (ST) and occupational therapy (OT). Overall, males
      were more likely to receive therapy services as well as a greater number of
      services than females. Autism status was significantly associated with both males
      and females receiving ST and males receiving OT and behaviour management therapy.
      Therapies were provided in a variety of locations, and parents were generally
      satisfied with the amount and quality of therapy services. Age-related declines
      were evident in the use of services for both males and females, with very few
      individuals receiving any therapy services after 20 years of age. CONCLUSIONS:
      This study provides a baseline description of the current state of therapy
      services for children with FXS, laying a foundation for future research and
      recommendations for service provision and policy.

PMID- 22974132
TI  - Electric bistability induced by incorporating self-assembled
      monolayers/aggregated clusters of azobenzene derivatives in pentacene-based thin
      film transistors.
AB  - Composite films of pentacene and a series of azobenzene derivatives are prepared
      and used as the active channel material in top-contact, bottom-gate field-effect
      transistors. The transistors exhibit high field-effect mobility as well as large
      I-V hysteresis as a function of the gate bias history. The azobenzene moieties,
      incorporated either in the form of self-assembled monolayer or discrete
      multilayer clusters at the dielectric surface, result in electric bistability of
      the pentacene-based transistor either by photoexcitation or gate biasing. The
      direction of threshold voltage shifts, size of hysteresis, response time, and
      retention characteristics all strongly depend on the substituent on the benzene
      ring. The results show that introducing a monolayer of azobenzene moieties
      results in formation of charge carrier traps responsible for slower switching
      between the bistable states and longer retention time. With clusters of
      azobenzene moieties as the trap sites, the switching is faster but the retention
      is shorter. Detailed film structure analyses and correlation with the
      transistor/memory properties of these devices are provided.

PMID- 22974131
TI  - Separate or combined treatments with daily sildenafil, molsidomine, or muscle
      derived stem cells prevent erectile dysfunction in a rat model of cavernosal
      nerve damage.
AB  - INTRODUCTION: Long-term daily administration of phosphodiesterase type 5 (PDE5)
      inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction
      (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and
      bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In
      the aging rat model, corporal implantation of skeletal muscle-derived stem cells
      (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can
      modulate stem cell lineage. AIM: To investigate in the BCNR model the effects of
      sildenafil at lower doses, alone or in combination with MDSC or the NO donor
      molsidomine, on CVOD and the underlying corporal histopathology. MAIN OUTCOMES
      MEASURES: CVOD, histological, and biochemical markers in rat corporal tissue.
      Methods.  Rats subjected to BCNR were maintained for 45 days either untreated, or
      received sildenafil in the water or retrolingually at 10, 2.5, and 1.25 mg/kg/day
      (medium, low, and very low doses), or intraperitoneal molsidomine, or MDSC
      implantation into the corpora cavernosa separately or in combination.
      Cavernosometry evaluated CVOD. Histopathology was assessed on penile sections by
      Masson trichrome, immunohistochemistry for alpha-smooth muscle actin (ASMA), or
      immunofluorescence for neuronal nitric oxide synthase (nNOS)/neurofilament 70,
      and in fresh tissue by Western blot for various markers and picrosirius red for
      collagen. RESULTS: All treatments normalized erectile function (drop rate), and
      most increased the CSMC/collagen ratio and ASMA expression in corporal tissue
      sections, and reduced collagen content in the penile shaft. MDSC also increased
      nNOS and brain-derived neurotrophic factor. The combination treatment was not
      superior to MDSC or sildenafil given alone, and upregulated PDE5. CONCLUSIONS:
      Lowering the dose of a continuous long-term sildenafil administration still
      maintained the prevention of CVOD in the BCNR rat previously observed, but it was
      less effective on the underlying histopathology. As in the aging rat model, MDSC
      also counteracted CVOD, but supplementation with very low-dose sildenafil did not
      improve the outcome.

PMID- 22974133
TI  - Structure-activity relationship for the development of a self-adjuvanting
      mucosally active lipopeptide vaccine against Streptococcus pyogenes.
AB  - Infection with group A streptococcus (GAS) can result in a number of diseases,
      some of which are potentially life-threatening. The oral-nasal mucosa is a
      primary site of GAS infection, and a mucosally active vaccine candidate could
      form the basis of an antidisease and transmission-blocking GAS vaccine. In the
      present study, a peptide from the GAS M protein (J14) representing a B cell
      epitope was incorporated alongside a universal T cell helper epitope and a Toll
      like receptor 2 targeting lipid moiety to form lipopeptide constructs. Through
      structure activity studies, we identified a vaccine candidate that induces J14
      specific mucosal and systemic antibody responses when administered intranasally
      without additional adjuvants. The systemic antibodies elicited were capable of
      inhibiting the growth of GAS. In addition, J14-specific mucosal antibodies
      corresponded with reduced throat colonization after respiratory GAS challenge.
      These preclinical experiments show that this lipopeptide could form the basis of
      an optimal needle-free mucosal GAS vaccine.

PMID- 22974134
TI  - Orbital intravascular papillary endothelial hyperplasia in a Nigerian child: a
      case report and review of the literature.
AB  - INTRODUCTION: Intravascular papillary endothelial hyperplasia is a reactive
      proliferative lesion of endothelial cells in blood vessels. It typically presents
      as a painless, reddish purple lesion in the sites affected. The orbit remains an
      uncommon site of affectation of this relatively common disease. It is noteworthy
      that this is the first reported case, to the best of our knowledge, of orbital
      intravascular papillary endothelial hyperplasia in a Nigerian child. CASE
      PRESENTATION: The case reported here is an orbital intravascular papillary
      endothelial hyperplasia causing non-axial proptosis and loss of vision in a 14
      year-old Nigerian boy. We describe the clinical and histological findings of
      intravascular papillary endothelial hyperplasia in the orbit of this 14-year-old
      boy. The key distinguishing features are discussed and relevant literature is
      reviewed. CONCLUSION: Although unusual in presentation, intravascular papillary
      endothelial proliferation should be considered in the list of differentials of
      proptosis due to mass lesion in young Nigerians and, possibly, Africans.

PMID- 22974135
TI  - Multiple-site concerted proton-electron transfer reactions of hydrogen-bonded
      phenols are nonadiabatic and well described by semiclassical Marcus theory.
AB  - Photo-oxidations of hydrogen-bonded phenols using excited-state polyarenes are
      described to derive fundamental understanding of multiple-site concerted proton
      electron transfer reactions (MS-CPET). Experiments have examined phenol bases
      having -CPh(2)NH(2), -Py, and -CH(2)Py groups ortho to the phenol hydroxyl group
      and tert-butyl groups in the 4,6-positions for stability (HOAr-NH(2), HOAr-Py,
      and HOAr-CH(2)Py, respectively; Py = pyridyl; Ph = phenyl). The photo-oxidations
      proceed by intramolecular proton transfer from the phenol to the pendent base
      concerted with electron transfer to the excited polyarene. For comparison, 2,4,6
      (t)Bu(3)C(6)H(2)OH, a phenol without a pendent base and tert-butyl groups in the
      2,4,6-positions, has also been examined. Many of these bimolecular reactions are
      fast, with rate constants near the diffusion limit. Combining the photochemical
      k(CPET) values with those from prior thermal stopped-flow kinetic studies gives
      data sets for the oxidations of HOAr-NH(2) and HOAr-CH(2)Py that span over 10(7)
      in k(CPET) and nearly 0.9 eV in driving force (DeltaG(o)'). Plots of log(k(CPET))
      vs DeltaG(o)', including both excited-state anthracenes and ground state aminium
      radical cations, define a single Marcus parabola in each case. These two data
      sets are thus well described by semiclassical Marcus theory, providing a strong
      validation of the use of this theory for MS-CPET. The parabolas give lambda(CPET)
      ? 1.15-1.2 eV and H(ab) ? 20-30 cm(-1). These experiments represent the most
      direct measurements of H(ab) for MS-CPET reactions to date. Although rate
      constants are available only up to the diffusion limit, the parabolas clearly
      peak well below the adiabatic limit of ca. 6 * 10(12) s(-1). Thus, this is a very
      clear demonstration that the reactions are nonadiabatic. The nonadiabatic
      character slows the reactions by a factor of ~45. Results for the oxidation of
      HOAr-Py, in which the phenol and base are conjugated, and for oxidation of 2,4,6
      (t)Bu(3)C(6)H(2)OH, which lacks a base, show that both have substantially lower
      lambda and larger pre-exponential terms. The implications of these results for MS
      CPET reactions are discussed.

PMID- 22974137
TI  - The impact of vitamin D on pregnancy: a systematic review.
AB  - Hypovitaminosis D is common in pregnancy. To systematically review the evidence
      on vitamin D-dependent pregnancy outcomes, PubMed and Embase were searched for
      randomized control trials, cohort and case-control studies. In randomized control
      trials (n = 7), larger doses of vitamin D resulted in higher 25-hydroxylated
      vitamin D (25OHD) levels (n = 6), increased maternal weight gain (n = 1), and
      fewer classical vitamin D deficiency symptoms (n = 1). In observational studies
      (n = 32), lower vitamin D intake, or low 25OHD-levels, were associated with
      adverse fertility parameters (n = 2), preeclampsia (n = 5), gestational diabetes
      or higher blood glucose (n = 6), bacterial vaginosis (n = 4), primary cesarean
      section (n = 1), none (n = 3) or a few days' (n = 2) shorter gestation, and
      postpartum depression (n = 1). Studies with few participants having low 25OHD did
      not identify an association to preeclampsia (n = 5) or gestational diabetes (n =
      2). Increased odds of pregnancy-associated breast cancer with 25OHD >25.8 nmol/L
      were observed (n = 1). In conclusion, an effect of vitamin D on several pregnancy
      outcomes is suggested.

PMID- 22974136
TI  - Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X
      DBA/2 J (BXD) recombinant inbred mouse strains.
AB  - BACKGROUND: miRNAs are short single-stranded non-coding RNAs involved in post
      transcriptional gene regulation that play a major role in normal biological
      functions and diseases. Little is currently known about how expression of miRNAs
      is regulated. We surveyed variation in miRNA abundance in the hippocampus of
      mouse inbred strains, allowing us to take a genetic approach to the study of
      miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is
      a very well characterized genetic reference panel which allows quantitative trait
      locus (QTL) analysis of miRNA abundance and detection of correlates in a large
      store of brain and behavioural phenotypes. RESULTS: We found five suggestive
      trans QTLs for the regulation of miRNAs investigated. Further analysis of these
      QTLs revealed two genes, Tnik and Phf17, under the miR-212 regulatory QTLs, whose
      expression levels were significantly correlated with miR-212 expression. We found
      that miR-212 expression is correlated with cocaine-related behaviour, consistent
      with a reported role for this miRNA in the control of cocaine consumption. miR-31
      is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis
      of each miRNA's expression correlates revealed enrichment of pathways including
      MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling.
      CONCLUSIONS: The BXD reference panel allowed us to establish genetic regulation
      and characterize biological function of specific miRNAs. QTL analysis enabled
      detection of genetic loci that regulate the expression of these miRNAs. eQTLs
      that regulate miRNA abundance are a new mechanism by which genetic variation
      influences brain and behaviour. Analysis of one of these QTLs revealed a gene,
      Tnik, which may regulate the expression of a miRNA, a molecular pathway and a
      behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and
      cocaine related behaviours is strongly supported by previous functional studies,
      demonstrating the value of this approach for discovery of new functional roles
      and downstream processes regulated by miRNA.

PMID- 22974138
TI  - Release of intracellular proteins by electroporation with preserved cell
      viability.
AB  - Extraction of intracellular proteins from cells is often an important first step
      for conducting molecular biology and proteomics studies. Although ultrasensitive
      detection and analytical technology at the single molecule level is becoming
      routine, protein extraction techniques have not followed suit and still call for
      complete lysis that leads to cell death. In principle, with refined extraction
      techniques, intracellular proteins can potentially be extracted without killing
      the cell. In this Letter, we demonstrate that electroporation is capable of
      releasing intracellular proteins from adherent Chinese hamster ovary cells while
      preserving the cell viability. By tuning the duration and intensity of an
      electric pulse, we were able to control the average amount of protein release and
      the percentage of viable cells after the operation. Our results indicate that a
      substantial fraction of the cell population was able to release proteins under
      electroporation and survive the procedure. Interestingly, at the single cell
      level, the probability for cell death does not increase with more protein
      release. This work paves the way to extracting and analyzing intracellular
      proteins while keeping cells live.

PMID- 22974139
TI  - Design and rationale of the Mechanical Retrieval and Recanalization of Stroke
      Clots Using Embolectomy (MR RESCUE) Trial.
AB  - RATIONALE: Multimodal imaging has the potential to identify acute ischaemic
      stroke patients most likely to benefit from late recanalization therapies. AIMS:
      The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots
      Using Embolectomy Trial is to investigate whether multimodal imaging can identify
      patients who will benefit substantially from mechanical embolectomy for the
      treatment of acute ischaemic stroke up to eight-hours from symptom onset. DESIGN:
      Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a
      randomized, controlled, blinded-outcome clinical trial. POPULATION STUDIED: Acute
      ischaemic stroke patients with large vessel intracranial internal carotid artery
      or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of
      symptom onset are eligible. The study sample size is 120 patients. STUDY
      INTERVENTION: Patients are randomized to endovascular embolectomy employing the
      Merci Retriever (Concentric Medical, Mountain View, CA) or the Penumbra System
      (Penumbra, Alameda, CA) vs. standard medical care, with randomization stratified
      by penumbral pattern. OUTCOMES: The primary aim of the trial is to test the
      hypothesis that the presence of substantial ischaemic penumbral tissue visualized
      on multimodal imaging (magnetic resonance imaging or computed tomography)
      predicts patients most likely to respond to mechanical embolectomy for treatment
      of acute ischaemic stroke due to a large vessel, intracranial occlusion up to
      eight-hours from symptom onset. This hypothesis will be tested by analysing
      whether pretreatment imaging pattern has a significant interaction with treatment
      as a determinant of functional outcome based on the distribution of scores on the
      modified Rankin Scale measure of global disability assessed 90 days post-stroke.
      Nested hypotheses test for (1) treatment efficacy in patients with a penumbral
      pattern pretreatment, and (2) absence of treatment benefit (equivalency) in
      patients without a penumbral pattern pretreatment. An additional aim will only be
      tested if the primary hypothesis of an interaction is negative: that patients
      treated with mechanical embolectomy have improved functional outcome vs. standard
      medical management.

PMID- 22974141
TI  - Circulating regeneration and resource recovery of flue gas desulfurization
      residuals using a membrane electroreactor: from lab concept to commercial scale.
AB  - Desulfurization residuals (using NaOH sorbent) were regenerated
      electrochemically, and at the same time sulfur in the flue gas was recovered as
      H(2)SO(4) and H(2) was produced as a clean energy. Since industrialization should
      always be the final goal to pursue for lab technologies and the evolution of
      pilot- and full-scale commercial reactors has taken place relatively slowly, this
      paper is aimed to develop an electroreactor on a sufficiently large scale to
      evaluate the application potential of the proposed regeneration process. The
      following key design parameters are discussed: (1) voltage distributions over
      electrode, membrane, and electrolyte; and (2) scaling up correlation based on lab
      scale reactor operation parameters. Thereafter, in the developed reactor, the
      desulfurization residuals using NaOH sorbent from a semidry flue gas
      desulfurization (FGD) facility of a power plant in Shandong Province were
      regenerated and it is significant to note that the electrochemical efficiency of
      the designed reactor is comparable to that of the chlor-alkali industry, showing
      that the technology is environmentally friendly and economically feasible. If
      this technology is to be employed for FGD, the facility could be a profit
      generating manufacturing part instead of a currently money-consuming burden for
      the plants.

PMID- 22974140
TI  - From intervention to impact: modelling the potential mortality impact achievable
      by different long-lasting, insecticide-treated net delivery strategies.
AB  - BACKGROUND: The current target of universal access to long-lasting, insecticide
      treated nets (LLIN) is 80% coverage to reduce malaria deaths by 75% by 2015. So
      far, campaigns have been the main channel for large-scale delivery of LLINs,
      however the World Health Organization has recommended that equal priority should
      be given to delivery via routine antenatal care (ANC) and immunization systems
      (EPI) to target pregnant women and children from birth. These various channels of
      LLIN delivery are targeted to children of different ages. Since risk of mortality
      varies with child age and LLIN effectiveness declines with net age, it was
      hypothesized that the age at which a child receives a new LLIN, and therefore the
      delivery channel, is important in optimizing the health impact of a net. METHODS:
      A simple dynamic mathematical model was developed of delivery and impact of LLINs
      among children under five years of age and their household members, incorporating
      data on age-specific malaria death rates, net use by household structure, and net
      efficacy over time. RESULTS: The presented analysis finds that supplementing a
      universal mass campaign with extra ANC delivery would achieve a 1.4 times higher
      mortality reduction than campaign delivery alone, reflecting that children born
      in the years between campaigns would otherwise have access to old nets or no nets
      at an age of high risk. The relative advantage of supplementary ANC delivery is
      still present though smaller if malaria transmission levels are lower or if there
      is a strong mass effect achieved by mass campaigns. CONCLUSION: These results
      indicate that LLIN delivery policies must take into account the age of greatest
      malaria risk. Emphasis should be placed on supporting routine delivery of LLINs
      to young children as well as campaigns.

PMID- 22974142
TI  - Repeat posterior lamellar grafting for recalcitrant lower eyelid retraction is
      effective.
AB  - PURPOSE: To review one surgeon's (J.H.O.) experience with repeat retractor
      release and posterior lamellar grafting in patients with residual lower eyelid
      retraction. To quantify the amount of eyelid elevation expected from each
      procedure. METHOD: Retrospective chart review of patients with repeat posterior
      lamellar grafting between 1992 and 2010. Patients were grouped into thyroid
      associated orbitopathy (TAO) and other causes. Hard palate mucosa or free
      tarsoconjunctiva grafts were used. Preoperative and postoperative inferior
      scleral show, lagophthalmos, superficial punctate keratopathy, and patient
      symptoms were recorded. Outcome measures were changes in scleral show and
      lagophthalmos with each procedure. Combined results were examined.Results in
      patients with TAO were analysed separately and compared with other etiologies.
      RESULTS: In this series, a single procedure is expected to reduce scleral show by
      a mean of 1.63 mm (76%) and lagophthalmos by a mean of 0.48 mm (55%). A second
      procedure can further reduce residual scleral show by a mean of 0.71 mm (80%) and
      residual lagophthalmos by a mean of 0.43 mm (76%). Patients with TAO were more
      likely to have larger measurements of preoperative scleral show (1.40 mm versus
      0.46 mm, p < 0.001). Patients with other etiologies were more likely to have
      larger measurements of preoperative lagophthalmos (1.25 mm versus 0.47 mm, p =
      0.004). CONCLUSIONS: This is the first study to evaluate outcomes of recalcitrant
      lower lid retraction requiring repeat posterior lamellar grafting. Mean
      reductions in scleral show and lagophthalmos can be used as a guide in the
      preoperative evaluation and counseling of patients with lower lid retraction.

PMID- 22974145
TI  - Numerical simulation of blood flow in the left ventricle and aortic sinus using
      magnetic resonance imaging and computational fluid dynamics.
AB  - Understanding cardiac blood flow patterns has many applications in analysing
      haemodynamics and for the clinical assessment of heart function. In this study,
      numerical simulations of blood flow in a patient-specific anatomical model of the
      left ventricle (LV) and the aortic sinus are presented. The realistic 3D geometry
      of both LV and aortic sinus is extracted from the processing of magnetic
      resonance imaging (MRI). Furthermore, motion of inner walls of LV and aortic
      sinus is obtained from cine-MR image analysis and is used as a constraint to a
      numerical computational fluid dynamics (CFD) model based on the moving boundary
      approach. Arbitrary Lagrangian-Eulerian finite element method formulation is used
      for the numerical solution of the transient dynamic equations of the fluid
      domain. Simulation results include detailed flow characteristics such as
      velocity, pressure and wall shear stress for the whole domain. The aortic outflow
      is compared with data obtained by phase-contrast MRI. Good agreement was found
      between simulation results and these measurements. 

PMID- 22974144
TI  - Differences in the profiles of DSM-IV and DSM-5 alcohol use disorders:
      implications for clinicians.
AB  - BACKGROUND: Existing information on consequences of the DSM-5 revision for the
      diagnosis of alcohol use disorders (AUD) has gaps, including missing information
      critical to understanding implications of the revision for clinical practice.
      METHODS: Data from Wave 2 of the National Epidemiologic Survey on Alcohol and
      Related Conditions were used to compare AUD severity, alcohol consumption and
      treatment, sociodemographic and health characteristics, and psychiatric
      comorbidity among individuals with DSM-IV abuse versus DSM-5 moderate AUD and DSM
      IV dependence versus DSM-5 severe AUD. For each pair of disorders, we
      additionally compared 3 mutually exclusive groups: individuals positive solely
      for the DSM-IV disorder, those positive solely for the DSM-5 disorder, and those
      positive for both. RESULTS: Whereas 80.5% of individuals positive for DSM-IV
      dependence were positive for DSM-5 severe AUD, only 58.0% of those positive for
      abuse were positive for moderate AUD. The profiles of individuals with DSM-IV
      dependence and DSM-5 severe AUD were almost identical. The only significant (p <
      0.005) difference, more AUD criteria among the former, reflected the higher
      criterion threshold (>= 4 vs. >= 3) for severe AUD relative to dependence. In
      contrast, the profiles of individuals with DSM-5 moderate AUD and DSM-IV abuse
      differed substantially. The former endorsed more AUD criteria, had higher rates
      of physiological dependence, were less likely to be White individuals and men,
      had lower incomes, were less likely to have private and more likely to have
      public health insurance, and had higher levels of comorbid anxiety disorders than
      the latter. CONCLUSIONS: Similarities between the profiles of DSM-IV and DSM-5
      AUD far outweigh differences; however, clinicians may face some changes with
      respect to appropriate screening and referral for cases at the milder end of the
      AUD severity spectrum, and the mechanisms through which these will be reimbursed
      may shift slightly from the private to public sector.

PMID- 22974148
TI  - Editor's note: term and termination.

PMID- 22974146
TI  - Endocytic structures and synaptic vesicle recycling at a central synapse in awake
      rats.
AB  - The synaptic vesicle (SV) cycle has been studied extensively in cultured cells
      and slice preparations, but not much is known about the roles and relative
      contributions of endocytic pathways and mechanisms of SV recycling in vivo, under
      physiological patterns of activity. We employed horseradish peroxidase (HRP) as
      an in vivo marker of endocytosis at the calyx of Held synapse in the awake rat.
      Ex vivo serial section scanning electron microscopy and 3D reconstructions
      revealed two categories of labelled structures: HRP-filled SVs and large
      cisternal endosomes. Inhibition of adaptor protein complexes 1 and 3 (AP-1, AP-3)
      by in vivo application of Brefeldin A (BFA) disrupted endosomal SV budding while
      SV recycling via clathrin-mediated endocytosis (CME) remained unaffected. In
      conclusion, our study establishes cisternal endosomes as an intermediate of the
      SV cycle and reveals CME and endosomal budding as the predominant mechanisms of
      SV recycling in a tonically active central synapse in vivo.

PMID- 22974149
TI  - Integrating empirically supported therapies for treating personality disorders: a
      synthesis of psychodynamic and cognitive-behavioral group treatments.
AB  - This paper describes the theoretical foundations and components of an intensive
      group treatment program for individuals diagnosed with personality disorders. The
      Chrysalis Community Day Treatment Program integrates aspects of three empirically
      supported therapies: Transference-Focused Psychotherapy and Mentalization-Based
      Therapy, both psychodynamic psychotherapies, and Dialectical Behavior Therapy, a
      cognitive-behavioral therapy. Each of these modalities is structured for the
      treatment of individuals suffering from the symptoms of borderline personality
      disorder, and each of the treatments addresses problems that occur across a wide
      spectra of beliefs, capacities, and behaviors. The program is comprised of
      expressive, psycho-educational and skills-training groups, and participants
      attend three days per week, for 15 weeks. Preliminary evaluation is promising,
      reflecting decreases in self-injurious behavior, suicide attempts, psychiatric
      hospitalizations, and psychiatric symptoms at a one-year follow-up.

PMID- 22974150
TI  - It's all about "me" (behold the leader).
AB  - The group beholds its leader: a looming figure of fantasy, an emerging figure of
      reality. Psychic patterns that play out in group cohesion, culture, conflicts,
      and process are rooted in interaction with this combined object. I describe a two
      day conference on relational group psychotherapy. An assemblage had beheld "me,"
      a visitor with gifts of knowledge, initially welcomed with collective
      expectation. Rivalrous and acquisitive desire (Girard, 2004) set group process in
      motion, involving scapegoating and open conflict, but also, self discovery and
      mutual appreciation. Confronted with "me," the representative, messenger, even
      embodiment of truth, the group had to deal with feelings, fantasies, and thoughts
      that were "not nice." There were moments of fear for the safety and survival of
      our group, yet I did not comprehend the extent to which envy, in tooth and nail,
      with devouring hunger tore into every aspect of our mentalities. Under its
      catabolic force, I was captured and I could not articulate to myself the sense of
      what it was, until the group shifted and released me from envy's intersubjective
      captivity. In group, whatever is being talked about-whoever is reacting to whom
      or to what-the group's focal conflict, predominating basic assumption,
      developmental level or stage, its regressions and progressions, dyadic
      interactions, subgroupings, and so forth, I now assume that on one level, it is
      all about "me."

PMID- 22974151
TI  - Passion, containment, and commitment-essential elements of groups across the
      lifespan in Bruce Springsteen's work.
AB  - The group, with its intensity, interaction, roles and dynamics, is an important
      unit of experience in everyday life, in psychotherapy groups, and in Bruce
      Springsteen's music. This paper explores experiences of and ideas about real life
      groups throughout the lifecycle through Springsteen's music, framed in concepts
      from a broad group literature including clinical psychology, social psychology,
      group psychotherapy, sociology, anthropology, and organizational psychology. The
      lifecycle includes adolescence and the role of the group to contain all its
      passions; the work world with its excitements and disillusionments; encounters
      with loss, and the holding power of the group; experiences of dissolution of the
      group, and possibilities for recommitment; and the passion and support of the
      group during celebrations. Themes of passion, containment, and commitment weave
      throughout the narrative.

PMID- 22974152
TI  - Suicide in group therapy: trauma and possibility.
AB  - This paper compares and contrasts the experiences of two different long term
      psychodynamic psychotherapy groups in which a patient suicided. The acute
      reactions and longer term process of each group is described in detail and
      discussed. The reactions of the two leaders, married to each other and in a
      shared supervisory group with the late Anne Alonso, and their own working through
      of the traumatic losses are explored. Their experiences highlight the importance
      of open discussion of the suicides in the groups, consultation with senior
      colleagues, and continual processing of their own reactions as a means of
      fostering posttraumatic growth. The authors discuss their experience in light of
      the literature on trauma in groups and the emerging literature on posttraumatic
      growth and they reflect on implications for the community of group therapists.

PMID- 22974153
TI  - AGPA annual meeting inspirations.

PMID- 22974154
TI  - The AGPA institute as a boost to therapist resilience in a post-9/11 world.

PMID- 22974155
TI  - Words to the members of the AGPA 2012 institute.

PMID- 22974156
TI  - Supervision: dragons and heroes.

PMID- 22974158
TI  - Effectiveness and cost-effectiveness of group versus individual motivational
      enhancement for substance use.

PMID- 22974163
TI  - In depth comparison of an individual's DNA and its lymphoblastoid cell line using
      whole genome sequencing.
AB  - BACKGROUND: A detailed analysis of whole genomes can be now achieved with next
      generation sequencing. Epstein Barr Virus (EBV) transformation is a widely used
      strategy in clinical research to obtain an unlimited source of a subject's DNA.
      Although the mechanism of transformation and immortalization by EBV is relatively
      well known at the transcriptional and proteomic level, the genetic consequences
      of EBV transformation are less well understood. A detailed analysis of the
      genetic alterations introduced by EBV transformation is highly relevant, as it
      will inform on the usefulness and limitations of this approach. RESULTS: We used
      whole genome sequencing to assess the genomic signature of a low-passage
      lymphoblastoid cell line (LCL). Specifically, we sequenced the full genome (40X)
      of an individual using DNA purified from fresh whole blood as well as DNA from
      his LCL. A total of 217.33 Gb of sequence were generated from the cell line and
      238.95 Gb from the normal genomic DNA. We determined with high confidence that
      99.2% of the genomes were identical, with no reproducible changes in structural
      variation (chromosomal rearrangements and copy number variations) or
      insertion/deletion polymorphisms (indels). CONCLUSIONS: Our results suggest that,
      at this level of resolution, the LCL is genetically indistinguishable from its
      genomic counterpart and therefore their use in clinical research is not likely to
      introduce a significant bias.

PMID- 22974164
TI  - Determination of the effects of aflatoxin B1 given in ovo on the proximal tibial
      growth plate of broiler chickens: histological, histometric and
      immunohistochemical findings.
AB  - Detrimental effects of aflatoxin B1 (AFB1) on the embryonic development of
      broiler tibia and its proximal growth plate were determined by means of
      histological, histometric and immunohistochemical methods. For this, 420 fertile
      eggs from parent stocks of Ross 308 broiler chickens were divided into five
      groups according to the proposed treatment: a control untreated group, a group
      injected with 30% ethanol and three further groups to be injected with 5, 15 or
      40 ng AFB1. The eggs were injected into the air space prior to incubation. Five
      eggs from each group were opened at 9, 11, 13, 17, 19 and 21 days of incubation
      and tibial tissue samples were removed, dissected of muscle and connective
      tissues, and processed by means of routine histological techniques. The cell
      proliferation rate of the epiphyseal growth plate cells was determined by
      immunohistochemical assay of proliferating cell nuclear antigen (PCNA)
      expression. The results showed that both proliferative and hypertrophic zones
      narrowed significantly (P<0.05), when compared with the controls, in all of the
      AFB1-treated groups whereas the transitional zone thickened, especially in the
      group given 40 ng AFB1 group. The PCNA positivity indices of 15 and 40 ng AFB1
      treated groups were significantly higher (P<0.05) on days 11, 13, 17, 19 and 21
      of incubation. It was concluded that in ovo-administered AFB1 adversely affected
      embryonic development of the tibial growth plate, and that affected hatched
      broilers might also be more susceptible to skeletal disorders during growth.

PMID- 22974165
TI  - Expression of c-Jun, p73, Casp9, and N-ras in thymic epithelial tumors:
      relationship with the current WHO classification systems.
AB  - BACKGROUND: To evaluate the expression and differential significance of c-Jun,
      p73, Casp-9 and N-ras in thymic epithelial tumors (TETs) with the aim to provide
      useful information for tumor biology and prospective therapy. METHODS: In this
      study, we analyzed the expression of four chromosome 1-related genes, namely c
      Jun, p73, Casp-9 and N-ras, in 60 cases of thymic epithelial tumors. The tumors
      included 52 thymomas and 8 thymic carcinomas which were categorized according to
      the current WHO classification systems. RESULTS: Compared with the normal thymus
      tissue, all thymic epithelial tumors demonstrated higher expression of c-Jun and
      p73. The expression of c-Jun and p73 in type B2, B3 thymoma and thymic carcinomas
      was similar, and significantly higher than that in all other subtypes of
      thymomas. Unlike type A thymoma, the expression of Casp-9 was relatively lower in
      type B thymoma and thymic carcinomas. With respect to the clinical staging
      systems, c-Jun was more expressed in progressive tumors harboring higher stages.
      In contrast to c-Jun, p73 and Casp-9, there was no significant aberration with N
      ras expression irrespective of either tissue or tumor types. CONCLUSIONS: The
      overexpression of c-Jun, p73 and Casp-9 in thymic epithelial tumors is closely
      related with the pathogenesis and biological behavior of the neoplasms. These
      candidate biomarkers provided useful information for prospective personalized
      therapy in the clinical management. VIRTUAL SLIDES:
      http://www.diagnosticpathology.diagnomx.eu/vs/1521774814749726.

PMID- 22974167
TI  - Early identification of autism in fragile X syndrome: a review.
AB  - Fragile X syndrome (FXS) is the leading genetic cause of autism, accounting for
      approximately 5% of autism cases with as many as 50% of individuals with FXS
      meeting DSM-IV-TR criteria for autistic disorder. Both FXS and idiopathic autism
      (IA) are attributed to genetic causes; however, FXS is an identified single gene
      disorder whereas autism is a complex disorder with multiple potential causes,
      some of which have been identified. Studies in IA have focused on the prospective
      longitudinal examination of infant siblings of children with autism as a target
      group due to their high risk of developing the disorder. We propose that this
      same model be applied to the study of infants with FXS. There is a lack of
      research focusing on the early development of autism within FXS and debate in the
      literature regarding how to best conceptualise this co-morbidity or whether it
      should be considered a co-morbid condition at all. Studying the emergence and
      stability of autism in infants with FXS has multiple benefits such as clarifying
      the underlying mechanisms of the development of autism in FXS and solidifying
      similarities and differences between co-morbid FXS with autism and IA. Infant
      research in both IA and FXS are discussed as well as conclusions and implications
      for practice and future research.

PMID- 22974169
TI  - Co-processed excipients: a patent review.
AB  - The introduction of high speed tableting machines and the preference of direct
      compression as a method of tableting have increased the demands on the
      functionality of excipients mainly in terms of flowability and compressibility.
      Co-processed excipients, where in, excipients are combined by virtue of sub
      particle level interaction have provided an attractive tool for developing high
      functionality excipients. The multifold advantages offered by co-processed
      excipients such as production of synergism in functionality of individual
      components, reduction of company's regulatory concern because of absence of
      chemical change during co-processing and improvement in physico-chemical
      properties have expanded their use in the pharmaceutical industry. In the recent
      years, there has been a spurt in the number of patents filed on co-processed
      excipients. Hence, the present review focuses on co-processed excipients and
      their application in pharmaceutical industry. The worldwide databases of European
      patent office (http://ep.espacenet.com) and United States patent office
      (www.uspto.gov) were employed to collect the patents and patent applications. The
      advantages, limitations, basis for the selection of excipients to be co
      processed, methods of co-processing and regulatory perspective of co-processed
      excipients are also briefly discussed.

PMID- 22974168
TI  - Intentionally retained pressure-regulating balloon in artificial urinary
      sphincter revision.
AB  - INTRODUCTION: The traditional surgical approach for revision of a malfunctioning
      artificial urinary sphincter (AUS) includes removal and replacement of all device
      components, identical to that employed in the setting of an infected or eroded
      AUS. AIMS:   To describe outcomes of our technique in which we intentionally
      leave behind the original pressure-regulating balloon (PRB) at time of AUS
      revision in a clinically non-infected setting. METHODS: We retrospectively
      reviewed our combined institutional series of 35 patients who underwent 36 AUS
      revisions in which the original pressure-regulating balloon was left undisturbed.
      We removed and replaced the defective cuff and pump through a single peno-scrotal
      incision for most patients requiring revision of a non-infected AUS. The new PRB
      was then placed on the opposite side through this single incision. MAIN OUTCOME
      MEASURES: Assessment of outcomes, complication, and infection rate of this
      surgical series. RESULTS: All of the patients had the original pressure
      regulating balloon placed through an inguinal counter-incision. Mean follow-up
      time was 14 months (2-33 months). Overall complication rate for the revision
      series was 11%. No infections or complications occurred secondary to the retained
      PRB. CONCLUSION: Follow-up of our series provides evidence that retention of the
      original PRB at the time of non-infected AUS revision is safe. Potential
      advantages include elimination of a counter incision and technically challenging
      exploration. By eliminating these aspects, the potentially resultant decreased
      operative time may help counter the theoretical yet unproven risk of infection
      from leaving the old PRB in place.

PMID- 22974166
TI  - Respiratory viral infections in children with asthma: do they matter and can we
      prevent them?
AB  - BACKGROUND: Asthma is a major public health problem with a huge social and
      economic burden affecting 300 million people worldwide. Viral respiratory
      infections are the major cause of acute asthma exacerbations and may contribute
      to asthma inception in high risk young children with susceptible genetic
      background. Acute exacerbations are associated with decreased lung growth or
      accelerated loss of lung function and, as such, add substantially to both the
      cost and morbidity associated with asthma. DISCUSSION: While the importance of
      preventing viral infection is well established, preventive strategies have not
      been well explored. Good personal hygiene, hand-washing and avoidance of
      cigarette smoke are likely to reduce respiratory viral infections. Eating a
      healthy balanced diet, active probiotic supplements and bacterial-derived
      products, such as OM-85, may reduce recurrent infections in susceptible children.
      There are no practical anti-viral therapies currently available that are suitable
      for widespread use. SUMMARY: Hand hygiene is the best measure to prevent the
      common cold. A healthy balanced diet, active probiotic supplements and
      immunostimulant OM-85 may reduce recurrent infections in asthmatic children.

PMID- 22974171
TI  - Pluripotent stem cell derivation and differentiation toward cardiac muscle: novel
      techniques and advances in patent literature.
AB  - Pluripotent stem cells hold unprecedented potential for regenerative medicine,
      disease modeling and drug screening. Embryonic stem cells (ESCs), standard model
      for pluripotency studies, have been recently flanked by induced pluripotent stem
      cells (iPSCs). iPSCs are obtained from somatic cells via epigenetic and
      transcriptional reprogramming, overcoming ESC-related ethical issues and enabling
      the possibility of donor-matching pluripotent cell lines. Since the European
      Court of Justice banned patents involving embryo disaggregation to generate human
      ESCs, iPSCs can now fuel the willingness of European companies to invest in
      treatments based on stem cells. Moreover, iPSCs share many unique features of
      ESCs, such as unlimited self-renewal potential and broad differentiation
      capability, even though iPSCs seem more susceptible to genomic instability and
      display epigenetic biases as compared to ESCs. Both ESCs and iPSCs have been
      intensely investigated for cardiomyocyte production and cardiac muscle
      regeneration, both in human and animal models. In vitro and in vivo studies are
      continuously expanding and refining this field via genetic manipulation and cell
      conditioning, trying to achieve standard and reproducible products, eligible for
      clinical and biopharmaceutical scopes. This review focuses on the recently
      growing body of patents, concerning technical advances in production, expansion
      and cardiac differentiation of ESCs and iPSCs.

PMID- 22974170
TI  - In vitro osteogenesis of human stem cells by using a three-dimensional perfusion
      bioreactor culture system: a review.
AB  - Tissue engineering (by culturing cells on appropriate scaffolds, and using
      bioreactors to drive the correct bone structure formation) is an attractive
      alternative to bone grafting or implantation of bone substitutes. Osteogenesis is
      a biological process that involves many molecular intracellular pathways
      organized to optimize bone modeling. The use of bioreactor systems and especially
      the perfusion bioreactor, provides both the technological means to reveal
      fundamental mechanisms of cell function in a 3D environment, and the potential to
      improve the quality of engineered tissues. In this mini-review all the
      characteristics for the production of an appropriate bone construct are analyzed:
      the stem cell source, scaffolds useful for the seeding of pre-osteoblastic cells
      and the effects of fluid flow on differentiation and proliferation of bone
      precursor cells. By automating and standardizing tissue manufacture in controlled
      closed systems, engineered tissues may reduce the gap between the process of bone
      formation in vitro and subsequent graft of bone substitutes in vivo.

PMID- 22974172
TI  - Severe acute T cell and antibody-mediated rejection in ectopic kidney allografts
      with or without mouse polyomavirus infection.

PMID- 22974173
TI  - Daily temperature and mortality: a study of distributed lag non-linear effect and
      effect modification in Guangzhou.
AB  - BACKGROUND: Although many studies have documented health effects of ambient
      temperature, little evidence is available in subtropical or tropical regions, and
      effect modifiers remain uncertain. We examined the effects of daily mean
      temperature on mortality and effect modification in the subtropical city of
      Guangzhou, China. METHODS: A Poisson regression model combined with distributed
      lag non-linear model was applied to assess the non-linear and lag patterns of the
      association between daily mean temperature and mortality from 2003 to 2007 in
      Guangzhou. The case-only approach was used to determine whether the effect of
      temperature was modified by individual characteristics, including sex, age,
      educational attainment and occupation class. RESULTS: Hot effect was immediate
      and limited to the first 5 days, with an overall increase of 15.46% (95%
      confidence interval: 10.05% to 20.87%) in mortality risk comparing the 99th and
      the 90th percentile temperature. Cold effect persisted for approximately 12 days,
      with a 20.39% (11.78% to 29.01%) increase in risk comparing the first and the
      10th percentile temperature. The effects were especially remarkable for
      cardiovascular and respiratory mortality. The effects of both hot and cold
      temperatures were greater among the elderly. Females suffered more from hot
      associated mortality than males. We also found significant effect modification by
      educational attainment and occupation class. CONCLUSIONS: There are significant
      mortality effects of hot and cold temperatures in Guangzhou. The elderly, females
      and subjects with low socioeconomic status have been identified as especially
      vulnerable to the effect of ambient temperatures.

PMID- 22974179
TI  - Switching off the tackiness of a nanocomposite adhesive in 30 s via infrared
      sintering.
AB  - Soft adhesives require an optimum balance of viscous and elastic properties.
      Adhesion is poor when the material is either too solidlike or too liquidlike. The
      ability to switch tack adhesion off at a desired time has many applications, such
      as in recycling, disassembly of electronics, and painless removal of wound
      dressings. Here, we describe a new strategy to switch off the tack adhesion in a
      model nanocomposite adhesive in which temperature is the trigger. The
      nanocomposite comprises hard methacrylic nanoparticles blended with a colloidal
      dispersion of soft copolymer particles. At relatively low volume fractions, the
      nanoparticles (50 nm diameter) accumulate near the film surface, where they pack
      around the larger soft particles (270 nm). The viscoelasticity of the
      nanocomposite is adjusted via the nanoparticle concentration. When the
      nanocomposite is heated above the glass transition temperature of the
      nanoparticles (T(g) = 130  degrees C), they sinter together to create a rigid
      network that raises the elastic modulus at room temperature. The tackiness is
      switched off. Intense infrared radiation is used to heat the nanocomposites,
      leading to a fast temperature rise. Tack adhesion is switched off within 30 s in
      optimized compositions. These one-way switchable adhesives have the potential to
      be patterned through localized heating.

PMID- 22974175
TI  - 46,XX ovotesticular disorder in a Mexican patient with Beckwith-Wiedemann
      syndrome: a case report.
AB  - INTRODUCTION: Beckwith-Wiedemann syndrome is an overgrowth syndrome that is
      characterized by hypoglycemia at birth, coarse face, hemihypertrophy and an
      increased risk to develop embryonal tumors. In approximately 15% of patients, the
      inheritance is autosomal dominant with variable expressivity and incomplete
      penetrance, whereas the remainder of Beckwith-Wiedemann syndrome cases are
      sporadic. Beckwith-Wiedemann syndrome molecular etiologies are complex and
      involve the two imprinting centers 1 (IC1) and 2 (IC2) of 11p15 region. This case
      report describes, for the first time, the unusual association of ovotesticular
      disorder in a patient from Morelia, Mexico with Wiedemann-Beckwith syndrome. CASE
      PRESENTATION: We report the case of a Mexican six-year-old girl with Beckwith
      Wiedemann Syndrome, ambiguous genitalia, and bilateral ovotestes. She has a 46,XX
      karyotype without evidence of Y-chromosome sequences detected by fluorescence in
      situ hybridization with both SRY and wcp-Y probes. CONCLUSION: Although a random
      association between these two conditions cannot be excluded, future analysis of
      this patient with Beckwith-Wiedemann syndrome and 46,XX ovotesticular disorder
      may lead to new insights into these complex pathologies. We speculate that a
      possible misregulation in the imprinted genes network has a fundamental role in
      the coexistence of these two disorders.

PMID- 22974176
TI  - Rare appearance of toxic epidermal necrolysis-like histopathological features in
      a case of atypical pemphigus with serological pemphigus vulgaris character.

PMID- 22974180
TI  - Sensitivity and specificity of a brief personality screening instrument in
      predicting future substance use, emotional, and behavioral problems: 18-month
      predictive validity of the Substance Use Risk Profile Scale.
AB  - BACKGROUND: This study assessed the validity, sensitivity, and specificity of the
      Substance Use Risk Profile Scale (SURPS), a measure of personality risk factors
      for substance use and other behavioral problems in adolescence. METHODS: The
      concurrent and predictive validity of the SURPS was tested in a sample of 1,162
      adolescents (mean age: 13.7 years) using linear and logistic regressions, while
      its sensitivity and specificity were examined using the receiver operating
      characteristics curve analyses. RESULTS: Concurrent and predictive validity tests
      showed that all 4 brief scales-hopelessness (H), anxiety sensitivity (AS),
      impulsivity (IMP), and sensation seeking (SS)-were related, in theoretically
      expected ways, to measures of substance use and other behavioral and emotional
      problems. Results also showed that when using the 4 SURPS subscales to identify
      adolescents "at risk," one can identify a high number of those who developed
      problems (high sensitivity scores ranging from 72 to 91%). And, as predicted,
      because each scale is related to specific substance and mental health problems,
      good specificity was obtained when using the individual personality subscales
      (e.g., most adolescents identified at high risk by the IMP scale developed
      conduct or drug use problems within the next 18 months [a high specificity score
      of 70 to 80%]). CONCLUSIONS: The SURPS is a valuable tool for identifying
      adolescents at high risk for substance misuse and other emotional and behavioral
      problems. Implications of findings for the use of this measure in future research
      and prevention interventions are discussed.

PMID- 22974178
TI  - Micronucleus scoring in liver fine needle aspiration cytology.
AB  - OBJECTIVE: This study evaluated the role of the micronucleus (MN) in liver fine
      needle aspiration (FNA) cytology. METHODS: Histological features of 75 cases of
      hepatocellular carcinoma (HCC), of which 25 were well differentiated, 37
      moderately differentiated and 13 poorly differentiated, and 58 benign hepatic
      lesions (total, 133 cases) were correlated with MN expression observed in FNA
      smears reported as benign (n =40), atypical (n = 14), suspicious (n = 30) and
      malignant (n =49). RESULTS: Stepwise increases in the MN score (0.4 +/- 0.6, 1.2
      +/- 1.3, 6.3 +/- 4.2 and 14.8 +/- 8.8) correlated with the degree of cytological
      abnormality: benign, atypia, suspicious and malignant, respectively. The mean MN
      scores for well-, moderately and poorly differentiated HCC were 5.4 +/- 2.2, 11.5
      +/- 4.5 and 24.9 +/- 9.1, respectively, which was significantly different between
      malignant and suspicious (P < 0.0001), between suspicious and atypical (P= 0.008)
      but not between atypical and benign. The MN scores differed significantly between
      all degrees of differentiation of HCC and between the HCC and benign hepatic
      lesions (P < 0.0001). High sensitivity, specificity and accuracy of liver FNA for
      diagnosing HCC (96%, 98%, and 96%, respectively) were obtained at a cutoff of
      three for the MN score. CONCLUSIONS: The MN score is an effective HCC biomarker
      and has a good potential use as an ancillary tool for diagnosing HCC using FNA
      cytology.

PMID- 22974181
TI  - Visible-light responsive photocatalytic fuel cell based on WO(3)/W photoanode and
      Cu(2)O/Cu photocathode for simultaneous wastewater treatment and electricity
      generation.
AB  - A visible-light driven photocatalytic fuel cell (PFC) system comprised of WO(3)/W
      photoanode and Cu(2)O/Cu photocathode was established for organic compounds
      degradation with simultaneous electricity generation. The central idea for its
      operation is the mismatched Fermi levels between the two photoelectrodes. Under
      light illumination, the Fermi level of WO(3)/W photoanode is higher than that of
      Cu(2)O/Cu photocathode. An interior bias can be produced based on which the
      electrons of WO(3)/W photoanode can transfer from the external circuit to combine
      with the holes of Cu(2)O/Cu photocathode then generates the electricity. In this
      manner, the electron/hole pairs separations at two photoelectrodes are
      facilitated to release the holes of WO(3)/W photoanode and electrons of Cu(2)O/Cu
      photocathode. Organic compounds can be decomposed by the holes of WO(3)/W
      photoanode due to its high oxidation power (+3.1-3.2 V(NHE)). The results
      demonstrated that various model compounds including phenol, Rhodamine B, and
      Congo red can be successfully decomposed in this PFC system, with the degradation
      rate after 5 h operation were obtained to be 58%, 63%, and 74%, respectively. The
      consistent operation for continuous water treatment with the electricity
      generation at a long time scale was also confirmed from the result. The proposed
      PFC system provides a self-sustained and energy-saving way for simultaneous
      wastewater treatment and energy recovery.

PMID- 22974174
TI  - A meta-analysis of intradermal versus intramuscular influenza vaccines:
      immunogenicity and adverse events.
AB  - OBJECTIVE: To determine immunogenicity and safety of intradermal (ID) influenza
      vaccines compared with intramuscular (IM) administration and effect of dose and
      age. DESIGN: Meta-anlysis. SETTING: Systematic review and meta-analysis of
      randomized controlled trials on influenza vaccines. SAMPLE: Randomized,
      controlled trials comparing ID seasonal split-virus influenza vaccines with 15
      MUg IM control in subjects 18 years of age or older and assessed antibody
      response at 21-28 days post-vaccination were considered for inclusion. RESULTS: A
      total of 13 trials were included. The pooled immunogenicity outcomes did not
      differ significantly between the IM and ID vaccine groups for the H1N1 (ratio of
      GMTR: 0.92, 95% confidence interval 0.77-1.09; seroconversion: 0.94, 0.86-1.02;
      seroprotection: 0.97, 0.94-1.00) and B strains (GMTR: 0.93, 0.80-1.08;
      seroconversion: 0.91, 0.80-1.04; seroprotection: 0.97, 0.91-1.03). For the H3N2
      strain, there was no significant difference in GMTR (0.97, 0.80-1.18); however,
      there was a lower pooled seroconversion (0.89, 0.80-0.99) and seroprotection rate
      (0.98, 0.96-0.99) for ID recipients. There was a statistically significant
      association between increasing doses of the ID vaccination with increasing
      immunogenicity response (P = 0.01). There were no differences in adverse event
      rates within 3 days post-vaccination for ID versus IM. But for adverse events
      occurring 7 days post-vaccination, ID vaccination was associated with a greater
      incidence of local events but not systemic events. CONCLUSIONS: There was no
      significant difference in immunologic response when comparing ID with IM
      administration of the influenza vaccination in the overall population, but higher
      doses of ID vaccine in the older adult population produced a better response.

PMID- 22974182
TI  - Feasibility and clinical effects of laparoscopic abdominal cerclage: an
      observational study.
AB  - OBJECTIVE: To evaluate the effect of laparoscopic abdominal cerclage performed as
      an interval procedure in non-pregnant women at high risk of second trimester
      spontaneous abortion and early preterm birth. DESIGN: Observational study.
      SAMPLE: Fifty-two consecutive patients at high risk of preterm birth. SETTING:
      Department of Obstetrics and Gynecology, Aarhus University Hospital. METHODS:
      Patients were registered prospectively. Indications for surgery included
      classical cervical insufficiency, preterm premature rupture of membranes (PPROM)
      or two conizations/cervical amputation. Outcome of subsequent pregnancies was
      registered. MAIN OUTCOME MEASURES: Gestational age in subsequent pregnancies.
      RESULTS: No operative or postoperative complications were observed. A total of 45
      pregnancies were registered during the observation period. Among 36 pregnancies
      lasting beyond the 16th week of gestation, 30 women (83.3%) gave birth by
      cesarean section after 36 weeks of gestation and the overall mean gestational age
      was 37.4 weeks compared with a mean gestational age of 25.2 weeks of the
      pregnancies prior to the cerclage. The cesarean sections were uncomplicated in
      all but one patient, where a re-laparotomy was needed six hours later due to
      atonic postpartum hemorrhage without evident bleeding through the cervix.
      CONCLUSION: Laparoscopic abdominal cerclage is a feasible and safe procedure.
      Obstetrical outcomes are encouraging but prospective studies are needed to define
      the effectiveness of the laparoscopic cerclage compared with the traditional
      transvaginal approach.

PMID- 22974177
TI  - Organic radical contrast agents for magnetic resonance imaging.
AB  - We report a molecular design that provides an intravenously injectable organic
      radical contrast agent (ORCA) for which the molecular (1)H water relaxivity
      (r(1)) is ca. 5 mM(-1) s(-1). The ORCA is based on spirocyclohexyl nitroxide
      radicals and poly(ethylene glycol) chains conjugated to a fourth-generation
      polypropylenimine dendrimer scaffold. The metal-free ORCA has a long shelf life
      and provides selectively enhanced magnetic resonance imaging in mice for over 1
      h.

PMID- 22974183
TI  - Tabula diptycha: differential HIV knowledge, stigma and intended behavioural
      outcomes amongst visitors at Vietnam's Pain and Hope exhibition.
AB  - Stigma reduction efforts in Vietnam have been encumbered by contradictory and
      dynamic views of people living with HIV and the epidemic over the past two
      decades. World AIDS Day 2010 saw the launch of Pain and Hope, a museum exhibition
      showcasing the lives and experiences of Vietnamese people living with AIDS at the
      Vietnam Museum of Ethnology (VME). Between December 2010 and May 2011, a random
      sample of visitors completed exit surveys regarding their attitudes towards the
      exhibition and Vietnamese living with HIV/AIDS. The survey sought to determine
      what kind of visitors the museum and exhibition attracted, and the stigma-related
      impacts of this kind of exposure and parasocial contact. Of 2500 Vietnamese
      visitors randomly selected, 852 completed the computer surveys (response rate of
      34.1%), 92.3% of whom had seen Pain and Hope. We found two sub-strata or types of
      visitors attending the exhibition, with varying demographic characteristics, HIV
      related knowledge, some differences in stigma ideation, and clear differences in
      intended behaviours specifically attributable to the exhibition. Social
      desirability biases notwithstanding, there has emerged a diptych typology of
      visitors to the VME, for whom the experience of the exhibition is likely
      interacting with divergent prior knowledge, experiences, interests and
      motivations. 

PMID- 22974185
TI  - Is the transverse acetabular ligament a reliable cup orientation guide?
AB  - BACKGROUND AND PURPOSE: It is controversial whether the transverse acetabular
      ligament (TAL) is a reliable guide for determining the cup orientation during
      total hip arthroplasty (THA). We investigated the variations in TAL anatomy and
      the TAL-guided cup orientation. METHODS: 80 hips with osteoarthritis secondary to
      hip dysplasia (OA) and 80 hips with osteonecrosis of the femoral head (ON) were
      examined. We compared the anatomical anteversion of TAL and the TAL-guided cup
      orientation in relation to both disease and gender using 3D reconstruction of
      computed tomography (CT) images. RESULTS: Mean TAL anteversion was 11 degrees 
      (SD 10, range -12 to 35). The OA group (least-square mean 16 degrees , 95%
      confidence interval (CI): 14-18) had larger anteversion than the ON group (least
      square mean 6.2 degrees , CI: 3.8 - 7.5). Females (least-square mean 20 degrees ,
      CI: 17-23) had larger anteversion than males (least-square mean 7.0 degrees , CI:
      4.6-9.3) in the OA group, while there were no differences between the sexes in
      the ON group. When TAL was used for anteversion guidance with the radiographic
      cup inclination fixed at 40 degrees , 39% of OA hips and 9% of ON hips had more
      than 10 degrees  variance from the target anteversion, which was 15 degrees .
      INTERPRETATION: In ON hips, TAL is a good guide for determining cup orientation
      during THA, although it is not a reliable guide in hips with OA secondary to
      dysplasia. This is because TAL orientation has large individual variation and is
      influenced by disease and gender.

PMID- 22974187
TI  - Global snapshot of the influence of endocytosis upon EGF receptor signaling
      output.
AB  - Trafficking of activated receptors may dictate the signaling output through the
      exposure to a changing palette of substrates and effectors. Here, we have used
      the acute application of a chemical inhibitor of dynamin activity, Dynasore, to
      inhibit internalization of activated EGF receptors together with quantitative
      mass spectrometry. This has generated a global snapshot of phosphorylation
      associated changes, which are contingent upon the endosomal trafficking of the
      activated EGF receptor. Using a SILAC approach, we have been able to quantitate
      >500 proteins in pTyr immunoprecipitation experiments and close to 800 individual
      phosphopeptides through affinity based enrichment strategies. This study provides
      >2 orders of magnitude increase in the coverage of potential EGF effectors than
      hitherto assessed in the context of endocytosis. There is a strong positive
      correlation between EGF responsiveness and sensitivity to Dynasore, with ~40% of
      EGF responses being significantly changed by endocytic inhibition. Proteins which
      are functionally linked to endosomal sorting are strongly influenced by receptor
      entry, suggesting that the activated receptor can govern its fate by influencing
      endosomal dynamics. However, the majority of EGF-responsive enzymes which we
      quantify, do not exhibit this property. Hence, our results provide many examples
      of key signaling proteins that are impervious to EGFR receptor endocytosis but
      nevertheless confirm the broad principle of endocytosis influence upon the
      network response.

PMID- 22974186
TI  - Alterations of microbiota in urine from women with interstitial cystitis.
AB  - BACKGROUND: Interstitial Cystitis (IC) is a chronic inflammatory condition of the
      bladder with unknown etiology. The aim of this study was to characterize the
      microbial community present in the urine from IC female patients by 454 high
      throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical
      composition, richness and diversity of the IC microbiota were determined and
      compared to the microbial profile of asymptomatic healthy female (HF) urine.
      RESULTS: The composition and distribution of bacterial sequences differed between
      the urine microbiota of IC patients and HFs. Reduced sequence richness and
      diversity were found in IC patient urine, and a significant difference in the
      community structure of IC urine in relation to HF urine was observed. More than
      90% of the IC sequence reads were identified as belonging to the bacterial genus
      Lactobacillus, a marked increase compared to 60% in HF urine. CONCLUSION: The 16S
      rDNA sequence data demonstrates a shift in the composition of the bacterial
      community in IC urine. The reduced microbial diversity and richness is
      accompanied by a higher abundance of the bacterial genus Lactobacillus, compared
      to HF urine. This study demonstrates that high throughput sequencing analysis of
      urine microbiota in IC patients is a powerful tool towards a better understanding
      of this enigmatic disease.

PMID- 22974188
TI  - Squaraine-arylamine sensitizers for highly efficient p-type dye-sensitized solar
      cells.
AB  - New near-IR (NIR) squaraine dyes (p-SQ1 and p-SQ2) containing one and two
      anchoring groups were synthesized and used as the sensitizers of p-type DSSCs.
      The dye (0.113%) with two anchoring groups (p-SQ2) shows better performance than
      the dye (0.053%) with only one anchoring group (p-SQ1). Cosensitized p-type DSSCs
      using two dyes with complementary absorption were tested. They have broadened
      IPCE spectra and good cell performance.

PMID- 22974189
TI  - Synthesis and N-H reductive elimination study of dinuclear ruthenium imido
      dihydride complexes.
AB  - Diruthenium imido dihydride complexes [(Cp*Ru)(2)(MU-NAr)(MU-H)(2)] (Ar = Ph
      (2a), p-MeOC(6)H(4) (2b), p-ClC(6)H(4) (2c), 2,6-Me(2)C(6)H(3) (2d); Cp* = eta(5)
      C(5)Me(5)) have been synthesized by hydrogenation of the corresponding bis(amido)
      complexes [Cp*Ru(MU-NHAr)](2) (1a-d). Reductive elimination of the N-H bond from
      2a-c in the presence of arene yields the amido hydride complexes [(Cp*Ru)(2)(MU
      NHAr)(MU-H)(MU-eta(2):eta(2)-arene)] containing a pi-bound arene. The rate and
      kinetic isotope effect for this reaction are consistent with a mechanism
      involving initial rate-determining reductive elimination of an N-H bond to
      produce the coordinatively unsaturated amido hydride species {(Cp*Ru)(2)(MU
      NHAr)(MU-H)} (A) followed by rapid trapping of this species by an arene. The
      existence of A is also supported by the reversible interconversion of
      [(Cp*Ru)(2)(MU-NHPh)(MU-H)(MU-eta(2):eta(2)-C(7)H(8))] with the tetranuclear
      complex [(Cp*Ru)(4)(MU(4)-NHPh)(MU-NHPh)(MU-H)(2)] (4), a dimerization product of
      A through a MU(4)-NHPh bridge. DFT calculations provide structures of A and
      transition states for the N-H reductive elimination. Two distinct reaction
      pathways are found for the N-H reductive elimination, one of which involves
      direct migration of a MU-hydride to the MU-NAr ligand, and the other involves
      formation of a transient terminal hydride species.

PMID- 22974190
TI  - A systematic review of the utility of antidepressant pharmacotherapy in the
      treatment of vulvodynia pain.
AB  - INTRODUCTION:   Antidepressants have often been recommended as a potential
      treatment for the management of vulvodynia. However, review of the evidence
      supporting this recommendation has not been systematically assessed. AIM:   To
      evaluate the efficacy of antidepressant pharmacotherapy in the treatment of
      vulvodynia. MAIN OUTCOME MEASURES:   An assessment of the methodological quality
      of published reports addressing the utility of antidepressants in the treatment
      of vulvodynia was undertaken. Several secondary outcomes generated in the
      existing literature were also examined. METHODS:   A comprehensive search of the
      available literature was conducted. RESULTS:   The search yielded 13 published
      reports, i.e., 2 randomized controlled trials, 1 quasi-experimental trial, 7 non
      experimental studies, and 3 case reports. A number of methodological shortcomings
      were identified in several of the reports with respect to study design including
      lack of clear inclusion/exclusion criteria, small sample sizes, lack of
      comparison groups, insufficient blinding, among others. The vast majority of
      studies utilized tricyclic antidepressants (TCAs). Evidence supporting the
      benefits of TCAs studied to date was limited, i.e., based largely upon
      descriptive reports but unsubstantiated by randomized controlled trials. There
      were no systematic investigations into the comparative efficacy of different
      antidepressant classes in the treatment of vulvodynia. CONCLUSION:   There is
      insufficient evidence to support the recommendation of antidepressant
      pharmacotherapy in the treatment of vulvodynia. Although some vulvodynia
      afflicted patients derive symptom relief from antidepressants, additional
      research is required to identify those characteristics that would predict those
      patients for whom antidepressants are more likely to be effective.

PMID- 22974191
TI  - Cerebral rheumatoid vasculitis: a case report.
AB  - INTRODUCTION: Central nervous system involvement in rheumatoid arthritis is
      infrequent. The most frequent neurological manifestations of rheumatoid arthritis
      are peripheral neuropathy and cervical spinal cord compression due to subluxation
      of the cervical vertebrae. Cerebral rheumatoid vasculitis is an uncommon and
      serious complication which can be life-threatening. CASE PRESENTATION: A 52-year
      old North African Tunisian Caucasian woman presented with a six-week history of
      headache. She had suffered seropositive and destructive rheumatoid arthritis for
      nine years without any extra-articular complications. Magnetic resonance imaging
      of the brain with the T2 sequence showed high-intensity signal images at the
      frontal and parietal cortico-subcortical junction suggesting hemispheric
      vasculitis. CONCLUSIONS: Cerebral vasculitis is an infrequent complication in
      rheumatoid arthritis which is associated with high morbidity and in some cases
      can be life-threatening. Early assessment and a high index of suspicion to
      recognize such complications are essential in managing these patients.

PMID- 22974192
TI  - Surface-initiated poly(3-methylthiophene) as a hole-transport layer for polymer
      solar cells with high performance.
AB  - In this work, uniform poly(3-methylthiophene) (P3MT) films are fabricated on
      indium-tin oxide (ITO) surfaces using surface-initiated Kumada catalyst-transfer
      polycondensation (SI-KCTP) from surface-bound arylnickel(II) bromide initiators.
      The P3MT interfacial layer is covalently bound to the ITO surface, thereby
      preventing possible delamination during the processing of additional layers.
      These surface-bound P3MT layers successfully serve as the hole-transport layer
      for solution-processed bulk heterojunction polymer solar cells. Efficiencies
      greater than 5% have been achieved on devices based on doped thin P3MT
      interfacial layers. Moreover, because of the excellent stability of the
      covalently immobilized P3MT on ITO substrates, devices based on reused P3MT/ITO
      substrates extracted from old devices exhibit efficiencies similar to those of
      the original devices.

PMID- 22974193
TI  - Is blood glucose on admission a predictor of mortality in adult acute pneumonia?
AB  - BACKGROUND: Even if hyperglycaemia is often identified as an independent risk
      factor for developing respiratory tract infection, only few studies have
      investigated this relationship. The aim of this study is to investigate if plasma
      glucose on admission is related with in-hospital mortality among patients with
      pneumonia and to identify the glycaemic range with significant reductions of
      mortality risks in non-intensive care patients. METHODS: Data come from
      administrative records of 1018 non-intensive care patients hospitalised with
      diagnosis of pneumonia. For every patient, administrative records were linked
      with the plasma glucose. A multivariate logistic regression model was performed
      in order to evaluate the associations between in-hospital mortality and a set of
      demographic and clinical variables. Plasma glucose was added to the model as
      restricted cubic spline; risk estimates for hypoglycaemic and hyperglycaemic
      patients have been derived on the basis of this nonlinear model and presented
      with two values of odds ratio (OR). RESULTS: The minimal risk of in-hospital
      mortality was found at plasma glucose levels of mean 86 mg/dL [95% confidence
      interval (CI) 61-102]. The adjusted OR of deaths for plasma glucose on admission
      for hypoglycaemic patients (below 86 mg/dL) is 0.78 (95% CI 0.62-0.98) for each
      10 mg/dL of decrease, whereas for hyperglycaemic patients (above 86 mg/dL), the
      OR is 1.33 (95% CI 1.07-1.66) for each 10 mg/dL of increase in plasma glucose.
      CONCLUSIONS: Our observations suggest that in non-intensive care patients,
      hypoglycaemia, as hyperglycaemia, is associated with in-hospital mortality.

PMID- 22974194
TI  - Mapping heatwave health risk at the community level for public health action.
AB  - BACKGROUND: Climate change poses unprecedented challenges, ranging from global
      and local policy challenges to personal and social action. Heat-related deaths
      are largely preventable, but interventions for the most vulnerable populations
      need improvement. Therefore, the prior identification of high risk areas at the
      community level is required to better inform planning and prevention. We aimed to
      demonstrate a simple and flexible conceptual framework relying upon satellite
      thermal data and other digital data with the goal of easily reproducing this
      framework in a variety of urban configurations. RESULTS: The study area
      encompasses Rennes, a medium-sized French city. A Landsat ETM + image (60 m
      resolution) acquired during a localized heatwave (June 2001) was used to estimate
      land surface temperature (LST) and derive a hazard index. A land-use regression
      model was performed to predict the LST. Vulnerability was assessed through census
      data describing four dimensions (socio-economic status, extreme age, population
      density and building obsolescence). Then, hazard and vulnerability indices were
      combined to deliver a heatwave health risk index. The LST patterns were quite
      heterogeneous, reflecting the land cover mosaic inside the city boundary, with
      hotspots of elevated temperature mainly observed in the city center. A spatial
      error regression model was highly predictive of the spatial variation in the LST
      (R2 = 0.87) and was parsimonious. Three land cover descriptors (NDVI, vegetation
      and water fractions) were negatively linked with the LST. A sensitivity analysis
      (based on an image acquired on July 2000) yielded similar results. Southern areas
      exhibited the most vulnerability, although some pockets of higher vulnerability
      were observed northeast and west of the city. The heatwave health risk map showed
      evidence of infra-city spatial clustering, with the highest risks observed in a
      north-south central band. Another sensitivity analysis gave a very high
      correlation between 2000 and 2001 risk indices (r = 0.98, p < 10-12).
      CONCLUSIONS: Building on previous work, we developed a reproducible method that
      can provide guidance for local planners in developing more efficient climate
      impact adaptations. We recommend, however, using the health risk index together
      with hazard and vulnerability indices to implement tailored programs because
      exposure to heat and vulnerability do not require the same prevention strategies.

PMID- 22974196
TI  - Effects of drift gas on collision cross sections of a protein standard in linear
      drift tube and traveling wave ion mobility mass spectrometry.
AB  - There has been a significant increase in the use of ion mobility mass
      spectrometry (IM-MS) to investigate conformations of proteins and protein
      complexes following electrospray ionization. Investigations which employ
      traveling wave ion mobility mass spectrometry (TW IM-MS) instrumentation rely on
      the use of calibrants to convert the arrival times of ions to collision cross
      sections (CCS) providing "hard numbers" of use to structural biology. It is
      common to use nitrogen as the buffer gas in TW IM-MS instruments and to calibrate
      by extrapolating from CCS measured in helium via drift tube (DT) IM-MS. In this
      work, both DT and TW IM-MS instruments are used to investigate the effects of
      different drift gases (helium, neon, nitrogen, and argon) on the transport of
      multiply charged ions of the protein myoglobin, frequently used as a standard in
      TW IM-MS studies. Irrespective of the drift gas used, recorded mass spectra are
      found to be highly similar. In contrast, the recorded arrival time distributions
      and the derived CCS differ greatly. At low charge states (7 <= z <= 11) where the
      protein is compact, the CCS scale with the polarizability of the gas; this is
      also the case for higher charge states (12 <= z <= 22) where the protein is more
      unfolded for the heavy gases (neon, argon, and nitrogen) but not the case for
      helium. This is here interpreted as a different conformational landscape being
      sampled by the lighter gas and potentially attributable to increased field
      heating by helium. Under nanoelectrospray ionization (nESI) conditions, where
      myoglobin is sprayed from an aqueous solution buffered to pH 6.8 with 20 mM
      ammonium acetate, in the DT IM-MS instrument, each buffer gas can yield a
      different arrival time distribution (ATD) for any given charge state.

PMID- 22974195
TI  - The association between expressed emotion, illness severity and subjective burden
      of care in relatives of patients with schizophrenia. Findings from an Italian
      population.
AB  - BACKGROUND: An appropriate understanding of the association between high
      Expressed Emotion (EE) in family members of people with schizophrenia, patients'
      and relatives' correlates is needed to improve adaptation of psychoeducational
      interventions in diverse cultures. The aim of this study was to test the
      hypothesis that relatives designated as high EE would report higher subjective
      burden of care, and would be associated with objective variables that indicate
      greater illness severity i.e. number of previous hospitalizations and duration of
      illness. METHODS: We performed secondary analyses of baseline data from a
      randomized controlled trial conducted in Italy. RESULTS: High-EE relatives
      reported more subjective burden of care in disturbed behaviours and adverse
      effects areas, but did not perceive more deficits in social role performances. As
      regards illness severity characteristics, neither the number of previous hospital
      admissions nor the duration of illness was associated with high-EE. However,
      patients' previous psychosocial functioning, as measured by educational
      attainments, seems to protect the relative from high-EE status. CONCLUSION: There
      is a need for cross-cultural comparisons of the subjective experience of distress
      and burden among high EE carers as a target for intervention, aimed at reducing
      family stress as much as improving patient outcomes.

PMID- 22974197
TI  - Delayed visual orienting responses in children with developmental and/or
      intellectual disabilities.
AB  - BACKGROUND: Assessment of higher visual processing functions mostly requires
      active cooperation of participants, which is problematic in children with
      intellectual disabilities (ID). To circumvent this, we applied remote eye
      tracking to quantify (ab)normal visual orienting responses in children with ID in
      terms of reaction times to visual stimuli. METHODS: We presented visual stimuli
      (cartoon, coherent form, and coherent motion) to 127 children (2-14 years) with
      developmental and/or ID (risk group) and simultaneously measured their orienting
      ocular motor responses. Reaction times to fixation (RTF) in the risk group were
      compared with RTF values of an age-matched control group. RESULTS: Overall, in
      72% of the children in the risk group, RTF values to cartoon were delayed, in 47%
      to form, and in 38% to motion. The presence of delayed reaction times was highest
      in the group of children >4 years with ID. CONCLUSION: Our data show that a
      majority of children with developmental and/or ID have delayed visual orienting
      responses. This suggests that this group has increased risk for higher visual
      processing dysfunctions. Future studies are planned to correlate abnormal
      orienting responses to type of brain damage and to dissociate the responses from
      ocular motor disorders.

PMID- 22974198
TI  - Scientific publications and research groups on alcohol consumption and related
      problems worldwide: authorship analysis of papers indexed in PubMed and Scopus
      databases (2005 to 2009).
AB  - BACKGROUND: The research of alcohol consumption-related problems is a
      multidisciplinary field. The aim of this study is to analyze the worldwide
      scientific production in the area of alcohol-drinking and alcohol-related
      problems from 2005 to 2009. METHODS: A MEDLINE and Scopus search on alcohol
      (alcohol-drinking and alcohol-related problems) published from 2005 to 2009 was
      carried out. Using bibliometric indicators, the distribution of the publications
      was determined within the journals that publish said articles, specialty of the
      journal (broad subject terms), article type, language of the publication, and
      country where the journal is published. Also, authorship characteristics were
      assessed (collaboration index and number of authors who have published more than
      9 documents). The existing research groups were also determined. RESULTS: About
      24,100 documents on alcohol, published in 3,862 journals, and authored by 69,640
      authors were retrieved from MEDLINE and Scopus between the years 2005 and 2009.
      The collaboration index of the articles was 4.83 +/- 3.7. The number of
      consolidated research groups in the field was identified as 383, with 1,933
      authors. Documents on alcohol were published mainly in journals covering the
      field of "Substance-Related Disorders," 23.18%, followed by "Medicine," 8.7%,
      "Psychiatry," 6.17%, and "Gastroenterology," 5.25%. CONCLUSIONS: Research on
      alcohol is a consolidated field, with an average of 4,820 documents published
      each year between 2005 and 2009 in MEDLINE and Scopus. Alcohol-related
      publications have a marked multidisciplinary nature. Collaboration was common
      among alcohol researchers. There is an underrepresentation of alcohol-related
      publications in languages other than English and from developing countries, in
      MEDLINE and Scopus databases.

PMID- 22974199
TI  - What is the novel clinical finding in dyschromatosis symmetrica hereditaria?

PMID- 22974201
TI  - Idebenone treatment mediates the effect of menadione oxidative stress damage in
      Saccharomyces cerevisiae.
AB  - We investigated the damage caused by oxidative stress using the yeast
      Saccharomyces cerevisiae as a model biological system. After inducing oxidative
      stress with menadione, we were able to evaluate the extent of cellular oxidative
      stress by utilizing 2',7'-dichlorofluorescein diacetate (DCFH-DA) as a marker of
      the presence of reactive oxygen species. Cells were grown on different carbon
      sources in order to compare fermentative and oxidative metabolism. Under these
      conditions we evaluated the effectiveness of idebenone (2,3-dimethoxy-5-methyl-6
      (10- hydroxydecyl)-1,4-benzoquinone) as a molecule that could relieve menadione
      induced growth inhibition in Saccharomyces cerevisiae.

PMID- 22974202
TI  - Pyro without fire: synthesis, structure, and reactivity of a dimeric vanadyl
      pyrophosphate coordination complex.
AB  - The complex {[(V(IV)O)bipy(H(2)O)](2)(MU-P(2)O(7))}.3H(2)O (2) was readily
      obtained as a nanocrystalline powder by one-pot synthesis under mild conditions.
      Single crystals of 2 were grown at room temperature over 2 months, and its
      structure was determined. Fundamental catalytic activity was proven for this
      species by testing for oxidation of benzyl alcohol in air.

PMID- 22974200
TI  - In silico evolutionary analysis of Helicobacter pylori outer membrane
      phospholipase A (OMPLA).
AB  - BACKGROUND: In the past decade, researchers have proposed that the pldA gene for
      outer membrane phospholipase A (OMPLA) is important for bacterial colonization of
      the human gastric ventricle. Several conserved Helicobacter pylori genes have
      distinct genotypes in different parts of the world, biogeographic patterns that
      can be analyzed through phylogenetic trees. The current study will shed light on
      the importance of the pldA gene in H. pylori. In silico sequence analysis will be
      used to investigate whether the bacteria are in the process of preserving,
      optimizing, or rejecting the pldA gene. The pldA gene will be phylogenetically
      compared to other housekeeping (HK) genes, and a possible origin via horizontal
      gene transfer (HGT) will be evaluated through both intra- and inter-species
      evolutionary analyses. RESULTS: In this study, pldA gene sequences were
      phylogenetically analyzed and compared with a large reference set of concatenated
      HK gene sequences. A total of 246 pldA nucleotide sequences were used; 207 were
      from Norwegian isolates, 20 were from Korean isolates, and 19 were from the NCBI
      database. Best-fit evolutionary models were determined with MEGA5 ModelTest for
      the pldA (K80 + I + G) and HK (GTR + I + G) sequences, and maximum likelihood
      trees were constructed. Both HK and pldA genes showed biogeographic clustering.
      Horizontal gene transfer was inferred based on significantly different GC
      contents, the codon adaptation index, and a phylogenetic conflict between a tree
      of OMPLA protein sequences representing 171 species and a tree of the AtpA HK
      protein for 169 species. Although a vast majority of the residues in OMPLA were
      predicted to be under purifying selection, sites undergoing positive selection
      were also found. CONCLUSIONS: Our findings indicate that the pldA gene could have
      been more recently acquired than seven of the HK genes found in H. pylori.
      However, the common biogeographic patterns of both the HK and pldA sequences
      indicated that the transfer occurred long ago. Our results indicate that the
      bacterium is preserving the function of OMPLA, although some sites are still
      being evolutionarily optimized.

PMID- 22974203
TI  - Structural imaging of schizophrenia: is the modern psychiatrist becoming a
      'disease scene investigator?': an editorial comment to Perlini C, Bellani M,
      Brambilla P. 'Structural imaging techniques in schizophrenia'.

PMID- 22974204
TI  - Metformin for schizophrenia: an editorial comment to Curtis J, Newall H, Shiers
      D, Samaras K. 'Considering metformin in cardiometabolic protection in psychosis'.

PMID- 22974205
TI  - The economic impact of mental health services and the need for cost reduction
      programs: suggestions from middle-income countries.

PMID- 22974210
TI  - Studies on silver nanoparticle-glycyrrhizic acid complex as a radioprotector and
      an adjuvant in radiotherapy under in vivo conditions.
AB  - Silver nanoparticles (SN) of particle size of less than 50 nm were dispersed in
      an aqueous solution of Pluronic F127 and complexed with the phytoceutical,
      glyzyrrhizic acid (GLY). Radioprotecting ability of the obtained nanoparticle
      glyzyrrhizic acid complex (SN-GLY) was evaluated in an in vivo model using Swiss
      albino mice. The potential of the complex as an adjuvant during radiotherapy was
      also analyzed in tumor-bearing mice. The administration of SN-GLY, SN, and GLY
      protected the hemopoetic and gastrointestinal system against radiation-induced
      damages as revealed by the total white blood cell count, bone marrow cellularity,
      endogenous spleen colony formation, levels of cellular antioxidants, and
      histopathologcal examination of gastrointestinal tract. Oral administration of SN
      GLY, SN, and GLY 1 hour before a sublethal dose of radiation exposure reduced the
      radiation-induced depletion of cellular antioxidants and lipid peroxidation in
      various tissues of mice. Survival of animals following exposure to a lethal dose
      of gamma radiation was also improved. It was also found that the oral
      administration of the complex to tumor-bearing mice before 4 Gy gamma irradiation
      resulted in a faster tumor regression.

PMID- 22974211
TI  - The natural history of clinical operational tolerance after kidney
      transplantation through twenty-seven cases.
AB  - We report here on a European cohort of 27 kidney transplant recipients displaying
      operational tolerance, compared to two cohorts of matched kidney transplant
      recipients under immunosuppression and patients who stopped immunosuppressive
      drugs and presented with rejection. We report that a lower proportion of
      operationally tolerant patients received induction therapy (52% without induction
      therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference
      likely due to the higher proportion (18.5%) of HLA matched recipients in the
      tolerant cohort. These patients were also significantly older at the time of
      transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than
      recipients who rejected their graft after weaning. Finally, these patients were
      at lower risk of infectious disease. Among the 27 patients defined as
      operationally tolerant at the time of inclusion, 19 still display stable graft
      function (mean 9 +/- 4 years after transplantation) whereas 30% presented slow
      deterioration of graft function. Six of these patients tested positive for pre
      graft anti-HLA antibodies. Biopsy histology studies revealed an active
      immunologically driven mechanism for half of them, associated with DSA in the
      absence of C4d. This study suggests that operational tolerance can persist as a
      robust phenomenon, although eventual graft loss does occur in some patients,
      particularly in the setting of donor-specific alloantibody.

PMID- 22974212
TI  - Keratins in colorectal epithelial function and disease.
AB  - Keratins are the largest subgroup of intermediate filament proteins, which are an
      important constituent of the cellular cytoskeleton. The principally expressed
      keratins (K) of the intestinal epithelium are K8, K18 and K19. The specific
      keratin profile of a particular epithelium provides it with strength and
      integrity. In the colon, keratins have been shown to regulate electrolyte
      transport, likely by targeting ion transporters to their correct location in the
      colonocytes. Keratins are highly dynamic and are subject to post-translational
      modifications including phosphorylation, acetylation and glycosylation. These
      affect the filament dynamics and hence solubility of keratins and may contribute
      to protection against degradation. Keratin null mice (K8(-/-) ) develop colitis,
      and abnormal keratin mutations have been shown to be associated with inflammatory
      bowel disease (IBD). Abnormal expression of K7 and K20 has been noted in colitis
      associated dysplasia and cancers. In sporadic colorectal cancers (CRCs) may be
      useful in predicting tumour prognosis; a low K20 expression is noted in CRCs with
      high microsatellite instability; and keratins have been noted as dysregulated in
      peri-adenomatous fields. Caspase-cleaved fragment of K18 (M30) in the serum of
      patients with CRC has been used as a marker of cancer load and to assess response
      to therapy. These data suggest an emerging importance of keratins in maintaining
      normal function of the gastrointestinal epithelium as well as being a marker of
      various colorectal diseases. This review will primarily focus on the biology of
      these proteins, physiological functions and alterations in IBD and CRCs.

PMID- 22974214
TI  - Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-gamma
      expression in SMP30 knockout mice.
AB  - Senescence marker protein (SMP) 30 knockout (KO) mice display symptoms of scurvy,
      including spontaneous bone fractures, and this was considered to be induced by a
      failure of collagen synthesis owing to vitamin C deficiency. However, low bone
      mineral density is also known to be associated with spontaneous bone fracture.
      Therefore, we investigated the effects of vitamin C deficiency on the balance
      between osteoblasts and osteoclasts in SMP30 KO mice as evidenced by
      histopathology. All mice were fed a vitamin C-free diet, and only one group (KV)
      mice were given water containing 1.5 g/l of vitamin C, whereas wild-type (WT) and
      KO mice were given normal drinking tap water without vitamin C for 16 weeks.
      After 16 weeks, all femur samples were removed for histopathological examination.
      The femurs of KO mice showed significantly reduced bone area and decreased number
      of osteoblasts compared with those of WT mice and KV mice. KO mice also exhibited
      the lowest level of alkaline phosphatase (ALP) expression in their femurs.
      However, KO mice showed the most elevated expression of the receptor activator of
      nuclear factor kappa-B ligand (RANKL). Moreover, KO mice had the strongest
      peroxisome proliferator-activated receptor (PPAR)-gamma expression level in their
      osteoblasts and the highest number of TUNEL-positive bone marrow cells.
      Therefore, we concluded that vitamin C deficiency plays an important role in
      spontaneous bone fracture by inhibiting osteoblast differentiation and promoting
      transition of osteoblasts to adipocytes, and this could in turn be related to the
      increased PPAR-gamma expression.

PMID- 22974213
TI  - Heterotopic mineralization (ossification or calcification) in tendinopathy or
      following surgical tendon trauma.
AB  - Heterotopic tendon mineralization (ossification or calcification), which may be a
      feature of tendinopathy or which may develop following surgical trauma (repair or
      graft harvest), has not received much attention. The purpose of this article is
      to review the prevalence, mechanisms and consequences of heterotopic tendon
      mineralization and to identify the gaps in our current understanding. We focus on
      endochondral heterotopic ossification and draw on knowledge of the mechanisms of
      this process in other tissues and conditions. Finally, we introduce a novel
      murine Achilles tendon needle injury model, which will enable us to further study
      the mechanisms and biomechanical consequences of tendon mineralization.

PMID- 22974215
TI  - MMP7 is a target of the tumour-associated antigen EpCAM.
AB  - Epithelial cell adhesion molecule (EpCAM) is a single-transmembrane protein,
      which is involved in numerous cellular processes including cell adhesion,
      proliferation, maintenance of stemness of embryonic cells and progenitors,
      migration and invasion. Activation of signal transduction by EpCAM is warranted
      by regulated intramembrane proteolysis and nuclear translocation of the
      intracellular domain EpICD. Here, we describe matrix metalloproteinase 7 (MMP7)
      as a target gene of EpCAM signalling viaEpICD nuclear translocation. EpCAM and
      MMP7 expression pattern and levels positively correlated in vitro and in vivo,
      and were strongly elevated in primary carcinomas of the head and neck area.
      Hence, MMP7 is a novel target of EpCAM signalling.

PMID- 22974216
TI  - Oral exposure to methylmercury modifies the prostatic microenvironment in adult
      rats.
AB  - Methylmercury (MeHg) is an environmental pollutant that is highly toxic to the
      central nervous system. As its effects on male reproductive system are poorly
      understood, this study was carried out to analyse the effects of MeHg on the rat
      prostate. To evaluate the MeHg toxicity on ventral prostate, three groups of
      adult male Wistar rats received oral doses of 0.5, 1.0 and 3.0 mg/kg MeHg,
      respectively, on a daily basis for 14 days. A fourth group was used as a control.
      The prostate weight was decreased in rats treated orally with 0.5 mg/kg MeHg
      compared to controls. Also, Hg concentration increased significantly in the
      prostate after treatments. There were reductions in serum testosterone levels and
      androgen receptor immunoreactivity in animals receiving 3.0 mg MeHg/kg. The
      stereological data showed changes in the prostatic epithelial, stromal and
      luminal compartments which varied according to the different doses.
      Histopathological alterations, such as chronic inflammation, stratified
      epithelial hyperplasia and epithelial inflammatory reactive atypia, were observed
      in the 0.5 mg/kg MeHg-treated group. Epithelial atrophy was observed in the 3.0
      mg/kg MeHg-treated group. In conclusion, the MeHg affects prostatic homoeostasis
      resulting in histopathological changes that may be relevant in the pathogenesis
      of prostatic disease.

PMID- 22974217
TI  - Effect of cypermethrin, carbendazim and their combination on male albino rat
      serum.
AB  - SUMMARY: Alpha-cypermethrin and carbendazim are synthetic; alpha-cypermethrin
      belongs to a class of synthetic pyrethroids and carbendazim belongs to the class
      of carbamate fungicides. The current study was carried out to evaluate the low
      dose exposure of individual and mixed forms of cypermethrin and carbendazim.
      alpha-cypermethrin was used at 0.06, 0.12, 0.30 and 0.60 mg/kg  body weight (bw),
      carbendazim was at 0.48, 0.96, 2.4 and 4.8 mg/kg bw and combined doses
      (cypermethrin: 0.06, 0.12, 0.30 and 0.60 mg/kg.bwt + carbendazim: 0.48, 0.96, 2.4
      and 4.8 mg/kg.bwt) for 12 h and 24 h. The biochemical parameters and serum markey
      enzymes were analysed. The biochemical parameters include serum total protein,
      glucose, cholesterol, urea, uric acid, calcium, phosphorous, albumin and
      creatinine and serum marker enzymes such as alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase
      (GGT) and amylase were ascertained. Results indicated simultaneous changes in
      serum marker enzyme activity (ALT, AST, ALP, GGT and amylase) and biochemical
      markers (*P < 0.05, **P < 0.01 and ***P < 0.001). The experimental results
      indicate that even low-dose use of the synthetic pyrethroid carbamate and their
      combined form results in consequential negative effects on cell function.

PMID- 22974218
TI  - Hepatoprotective effect of Bathysa cuspidata in a murine model of severe toxic
      liver injury.
AB  - The objective of this study was to investigate the hepatoprotective effect of a
      bark extract of Bathysa cuspidata extract (BCE) in a murine model of severe liver
      injury induced by carbon tetrachloride (CCl(4) ). Forty-two Wistar rats were
      randomized into six groups of seven animals each: Group 1(G1): CCl(4) ; Group 2
      (G2): dimethyl sulfoxide (DMSO) + CCl(4) ; Group 3 (G3): BCE 400 mg/kg alone;
      Group 4 (G4): BCE 200 mg/kg + CCl(4) ; Group 5 (G5): BCE 400 mg/kg + CCl(4) ;
      Group 6 (G6): DMSO alone. The extract was administered by gavage for 18 days
      beginning 6 days prior to the first application of CCl(4) . After completing
      CCl(4)  administration, the animals were euthanized. The animals in G1, G2, G4
      and G5 experienced significant body weight loss and had an increased liver
      somatic index compared with G3 and G6 (P < 0.05). A significant reduction in
      serum aspartate and alanine transaminase and gamma-glutamyl transferase (P <
      0.05) and a significant increase in the activity of the anti-oxidant enzyme
      superoxide dismutase were found in G5 (P < 0.05). Lower proportions of cellular
      necrosis and lipid droplets were found in the livers of animals in G4 and G5
      compared with G1 and G2 (P < 0.05). These results confirm the marked
      hepatoprotective activity of the bark extract of Bathysa cuspidata in severe
      injuries induced by CCl(4)  in rats and suggest that this effect may be
      associated with the inhibition of oxidative damage.

PMID- 22974219
TI  - The role of repeatedly heated soybean oil in the development of hypertension in
      rats: association with vascular inflammation.
AB  - Thermally oxidized oil generates reactive oxygen species that have been
      implicated in several pathological processes including hypertension. This study
      was to ascertain the role of inflammation in the blood pressure raising effect of
      heated soybean oil in rats. Male Sprague-Dawley rats were divided into four
      groups and were fed with the following diets, respectively, for 6 months: basal
      diet (control); fresh soybean oil (FSO); five-time-heated soybean oil (5HSO); or
      10-time-heated soybean oil (10HSO). Blood pressure was measured at baseline and
      monthly using tail-cuff method. Plasma prostacyclin (PGI(2) ) and thromboxane
      A(2)  (TXA(2) ) were measured prior to treatment and at the end of the study.
      After six months, the rats were sacrificed, and the aortic arches were dissected
      for morphometric and immunohistochemical analyses. Blood pressure was increased
      significantly in the 5HSO and 10HSO groups. The blood pressure was maintained
      throughout the study in rats fed FSO. The aortae in the 5HSO and 10HSO groups
      showed significantly increased aortic wall thickness, area and circumferential
      wall tension. 5HSO and 10HSO diets significantly increased plasma TXA(2) /PGI(2) 
      ratio. Endothelial VCAM-1 and ICAM-1 were significantly increased in 5HSO, as
      well as LOX-1 in 10HSO groups. In conclusion, prolonged consumption of repeatedly
      heated soybean oil causes blood pressure elevation, which may be attributed to
      inflammation.

PMID- 22974220
TI  - Tourniquet use in total knee replacement does not improve fixation, but appears
      to reduce final range of motion.
AB  - BACKGROUND AND PURPOSE: Although a tourniquet may reduce bleeding during total
      knee replacement (TKA), and thereby possibly improve fixation, it might also
      cause complications. Migration as measured by radiostereometric analysis (RSA)
      can predict future loosening. We investigated whether the use of a tourniquet
      influences prosthesis fixation measured with RSA. This has not been investigated
      previously to our knowledge. METHODS: 50 patients with osteoarthritis of the knee
      were randomized to cemented TKA with or without tourniquet. RSA was performed
      postoperatively and at 6 months, 1 year, and 2 years. Pain during hospital stay
      was registered with a visual analog scale (VAS) and morphine consumption was
      measured. Overt bleeding and blood transfusions were registered, and total
      bleeding was estimated by the hemoglobin dilution method. Range of motion was
      measured up to 2 years. RESULTS: RSA maximal total point motion (MTPM) differed
      by 0.01 mm (95% CI -0.13 to 0.15). Patients in the tourniquet group had less
      overt bleeding (317 mL vs. 615 mL), but the total bleeding estimated by
      hemoglobin dilution at day 4 was only slightly less (1,184 mL vs. 1,236 mL) with
      a mean difference of -54 mL (95% CI -256 to 152). Pain VAS measurements were
      lower in the non-tourniquet group (p = 0.01). There was no significant difference
      in morphine consumption. Range of motion was 11 degrees  more in the non
      tourniquet group (p = 0.001 at 2 years). INTERPRETATION: Tourniquet use did not
      improve fixation but it may cause more postoperative pain and less range of
      motion.

PMID- 22974221
TI  - A method to quantify infection and colonization of holm oak (Quercus ilex) roots
      by Phytophthora cinnamomi.
AB  - Phytophthora cinnamomi Rands. is an important root rot pathogen widely
      distributed in the north hemisphere, with a large host range. Among others
      diseases, it is known to be a principal factor in the decline of holm oak and
      cork oak, the most important tree species in the "dehesa" ecosystem of south
      western Spain. Previously, the focus of studies on P. cinnamomi and holm oak have
      been on molecular tools for identification, functional responses of the host,
      together with other physiological and morphological host variables. However, a
      microscopic index to describe the degree of infection and colonization in the
      plant tissues has not yet been developed. A colonization or infection index would
      be a useful tool for studies that examine differences between individuals
      subjected to different treatments or to individuals belonging to different
      breeding accessions, together with their specific responses to the pathogen. This
      work presents a methodology based on the capture and digital treatment of
      microscopic images, using simple and accessible software, together with a range
      of variables that quantify the infection and colonization process.

PMID- 22974222
TI  - Current trends in microsponge drug delivery system.
AB  - Microsponge is a microscopic sphere capable of absorbing skin secretions,
      therefore reducing the oiliness of the skin. Microsponge having particle size of
      10-25 microns in diameter, have wide range of entrapment of various ingredients
      in a single microsponges system and release them at desired rates. Conventional
      topical preparations have various disadvantages due to irritancy, odour,
      greasiness and patient compliance. In many topical dosage forms fail to reach the
      systemic circulation in sufficient amounts in few cases. These problems overcome
      by the usage of formulation as microsponge in the areas of research. Drug release
      in microsponge is done by the external stimuli like pH, temperature and rubbing.
      It has several advantageous over the other topical preparations in being non
      allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are
      used in the sun screens, creams, ointments, over-the-counter skin care
      preparations, recently nanosponge were reported in literature used in delivery of
      drug by the use of cyclodextrins to enhance the solubility of poorly water
      soluble drugs, which are meant for topical application. 

PMID- 22974223
TI  - Epidermal growth factor receptor activation and inhibition in 3D in vitro models
      of normal skin and human cutaneous squamous cell carcinoma.
AB  - The transmembrane tyrosine kinase epidermal growth factor receptor (EGFR) is
      considered a key player in the development of cutaneous squamous cell carcinoma
      (SCC), which is the second most common malignancy in white populations.
      Inhibition of EGFR with the small molecule tyrosine kinase inhibitor erlotinib is
      currently under clinical investigation in cutaneous SCC patients. In this study,
      we investigated the effects of EGFR activation and inhibition on normal and
      malignant in vitro human skin equivalents (HSEs). In healthy HSEs, increasing EGF
      concentrations ranging from 5 to 50 ng/mL resulted in a dramatic decrease in
      epidermal proliferation as immunohistochemically assessed by Ki67 and increased
      epidermal stress as assessed by K17 after 2 weeks of air-exposed culture. Also,
      higher concentrations of EGF induced remarkable epidermal disorganization with
      loss of proper stratification. Similar effects were observed in HSEs generated
      with cutaneous SCC cell lines SCC-12B2 and SCC-13. Treatment of both healthy and
      SCC-HSEs with 10 MUM erlotinib resulted in efficient reduction of epidermal
      thickness from 10 to 3 viable cell layers and counteracted EGF-induced epidermal
      stress. Remarkably, erlotinib treatment caused severe desquamation in healthy
      HSEs, reminiscent of xerosis as a known side-effect in patients treated with
      erlotinib. The presented three-dimensional organotypic SCC models appear suitable
      for further investigations on the morphological and functional impacts of
      modifying EGFR signaling in cutaneous SCC, without burdening patients or mice.
      The effective inhibition of epidermal growth by erlotinib in our HSEs confirms
      the therapeutic potential of this tyrosine kinase inhibitor for cutaneous SCC
      patients.

PMID- 22974224
TI  - Quantification of new structural features of coronary plaques by computational
      post-hoc analysis of virtual histology-intravascular ultrasound images.
AB  - Cardiovascular disease and complications are often mediated by the development
      and rupture of atherosclerotic plaques. Plaque composition is a major factor that
      determines plaque vulnerability. Intravascular ultrasound (IVUS) and spectral
      analysis of the radio frequency signal provide an in vivo tissue characterisation
      of atherosclerotic plaques, known as virtual histology (VH-IVUS). In VH-IVUS
      analysis, four histological tissue components are classified: fibrous,
      fibro/fatty, necrotic core and calcium. Existing technology determines only the
      area of each component within the plaque. Quantitative, objective
      characterisation of other plaque components' patterns within the plaque is
      lacking. The aim of this study was to determine new compositional and structural
      indices which indicate spatial distribution, heterogeneity and dispersity of each
      VH-IVUS-derived component within the plaque area and also with respect to the
      plaque-lumen border. We developed an automated computational system in Java for
      the analysis of both single cross-sectional segments and the whole length of the
      examined plaque (volumetric analysis). The following parameters were computed:
      the number of different solid segments and the area of the largest solid segment
      of each component within the plaque, the per cent of the lumen border that is
      surrounded by each component, the number of different solid segments and the
      largest area of a solid segment of each component that adjoins the lumen border.
      Especially components' localisation in relation to the lumen border may
      significantly influence plaque vulnerability and plaque-stent interaction, which
      should be investigated in future clinical studies. 

PMID- 22974225
TI  - 'Many people know the law, but also many people violate it': discrimination
      experienced by people living with HIV/AIDS in Vietnam--results of a national
      study.
AB  - In Vietnam, discrimination against people living with HIV/AIDS (PLHIV) is defined
      within and prohibited by the 2007 national HIV/AIDS law. Despite the law, PLHIV
      face discrimination in health care, employment, education and other spheres. This
      study presents the first national estimates of the levels and types of
      discrimination that are defined in Vietnamese law and experienced by PLHIV in
      Vietnam. A nationally representative sample of 1200 PLHIV was surveyed, and 129
      PLHIV participated in focus group discussions (FGDs). In the last 12 months,
      nearly half of the survey population experienced at least one form of
      discrimination and many experienced up to six different types of discrimination.
      The most common forms of discrimination included disclosure of HIV status without
      consent; denial of access to education for children; loss of employment; advice,
      primarily from health care providers, to abstain from sex; and physical and
      emotional harm. In logistic regression analysis, the experience of discrimination
      differed by gender, region of residence and membership status in a PLHIV support
      group. The logistic regression and FGD results indicate that disclosure of HIV
      status without consent was associated with experiencing other forms of
      discrimination. Key programme and policy recommendations are discussed. 

PMID- 22974226
TI  - Communication during pediatric asthma visits and child asthma medication device
      technique 1 month later.
AB  - OBJECTIVE: This study investigated how provider demonstration of and assessment
      of child use of asthma medication devices and certain aspects of provider-patient
      communication during medical visits is associated with device technique 1 month
      later. METHODS: Two hundred and ninety-six children aged 8-16 years with
      persistent asthma and their caregivers were recruited at five North Carolina
      pediatric practices. All of the medical visits were audio-tape recorded. Children
      were interviewed 1 month later and their device technique was observed and rated.
      RESULTS: If the provider asked the child to demonstrate metered dose inhaler
      technique during the medical visit, then the child was significantly more likely
      to perform a greater percentage of inhaler steps correctly 1 month later.
      Children with higher asthma management self-efficacy scores were significantly
      more likely to perform a greater percentage of diskus steps correctly.
      Additionally, children were significantly more likely to perform a greater
      percentage of diskus steps correctly if the provider discussed a written action
      plan during the visit. Children were significantly more likely to perform a
      greater percentage of turbuhaler steps correctly if they asked more medication
      questions. CONCLUSIONS: Providers should ask children to demonstrate their
      inhaler technique during medical visits so that they can educate children about
      proper technique and improve child asthma management self-efficacy. Providers
      should encourage children to ask questions about asthma medication devices during
      visits and they should discuss asthma action plans with families.

PMID- 22974227
TI  - Common pitfalls in some of the experimental studies in erectile function and
      dysfunction: a consensus article.
AB  - INTRODUCTION: Experimental studies investigating physiology of erectile function
      and pathophysiology erectile dysfunction employ several in vitro and in vivo
      techniques. As the field of sexual medicine expanding, the proper conduct of such
      techniques is becoming an even more important necessity than before. AIM: This
      review article aims to guide scientists, particularly young researchers and new
      comers in the field, toward employment of these techniques in an appropriate,
      timely, and competent fashion. METHODS: The authors reviewed the existing
      available published articles on the following topics: intracavernosal pressure
      measurements, cavernous nerve injury models, nitric oxide-cyclic guanosine
      monophosphate pathway, hypertension- and smoking-induced erectile dysfunction
      models, and stem cells. RESULTS: The authors present a consensus on how to best
      perform these models and techniques and also highlight the pitfalls. CONCLUSIONS:
      The authors hope that this article will assist and encourage young scientists in
      the field and that similar articles covering other important models will be also
      available to them soon.

PMID- 22974228
TI  - Unique radical dearomatization and two-electron reduction of a redox-active
      ligand.
AB  - The syntheses and characterizations of [Li(4)][(1,2-di-(tert-butyl)-dpp-BIAN)(2)]
      (7), (1,2-di-(tert-butyl)-dpp-BIAN) (8), and (1-(tert-butyl)-2-OH-dpp-BIAN) (9)
      are described. Compound 7 was formed via a radical dearomatization, two-electron
      reduction pathway that was accompanied by vicinal di-tert-butylation of the BIAN
      ligand backbone. Oxidation of 7 afforded a dearomatized vicinal di-tert-butyl
      substituted BIAN ligand (8). An analogous dearomatized vicinal tert-butyl-hydroxy
      substituted BIAN ligand (9) was also isolated in the course of mechanistic
      studies related to the formation of 7.

PMID- 22974229
TI  - Palladium-catalyzed intramolecular C-H arylation of arenes using tosylates and
      mesylates as electrophiles.
AB  - This paper describes a method for the palladium catalyzed intramolecular C-H
      arylation using tosylates and mesylates as electrophiles. The transformation is
      efficient for the synthesis of various heterocyclic motifs including furans,
      carbazoles, indoles, and lactams. Additionally, a protocol for the one-pot
      sequential tosylation/arylation of phenol derivatives is presented.

PMID- 22974230
TI  - Characterization of genes involved in ceramide metabolism in the Pacific oyster
      (Crassostrea gigas).
AB  - BACKGROUND: The lipid signaling molecule, ceramide, is a key component of the
      vertebrate stress response, however, there is limited information concerning its
      role in invertebrate species. In order to identify genes involved in ceramide
      metabolism in bivalve molluscs, Pacific oyster genomic resources were examined
      for genes associated with ceramide metabolism and signaling. RESULTS: Several
      genes were identified including full-length sequences characterized for serine
      palmitoyltransferase-1, 3-ketodihydrosphingosine reductase, acid ceramidase, and
      ceramide glucosyltransferase. Genes involved in ceramide synthesis and metabolism
      are conserved across taxa in both form and function. Expression analysis as
      assessed by quantitative PCR indicated all genes were expressed at high levels in
      gill tissue. The role of the ceramide pathway genes in the invertebrate stress
      response was also explored by measuring expression levels in adult oysters
      exposed to Vibrio vulnificus. Two genes demonstrated increased expression during
      the bacterial challenge: a gene involved in hydrolytic breakdown of ceramide
      (acid ceramidase) and a gene involved in de novo generation of ceramide (3
      ketodihydrosphingosine reductase), suggesting a possible role of ceramide in the
      invertebrate stress and immune responses. CONCLUSIONS: In silico and laboratory
      results support that Pacific oysters have the basic components of the ceramide
      metabolism pathway. These results also indicate that ceramide may have analogous
      functions in vertebrates and invertebrates. The gene expression pattern of acid
      ceramidase and 3-kethodihydrosphingosine reductase in response to bacterial
      exposure especially supports that ceramide and sphingolipid metabolism may be
      involved in the oyster's stress and/or immune responses.

PMID- 22974231
TI  - Continuous glucose monitoring: quality of hypoglycaemia detection.
AB  - AIMS: To evaluate the accuracy of a (widely used) continuous glucose monitoring
      (CGM)-system and its ability to detect hypoglycaemic events. METHODS: A total of
      18 patients with type 1 diabetes mellitus used continuous glucose monitoring
      (Guardian REAL-Time CGMS) during two 9-day in-house periods. A hypoglycaemic
      threshold alarm alerted patients to sensor readings <70 mg/dl. Continuous glucose
      monitoring sensor readings were compared to laboratory reference measurements
      taken every 4 h and in case of a hypoglycaemic alarm. RESULTS: A total of 2317
      paired data points were evaluated. Overall, the mean absolute relative difference
      (MARD) was 16.7%. The percentage of data points in the clinically accurate or
      acceptable Clarke Error Grid zones A + B was 94.6%. In the hypoglycaemic range,
      accuracy worsened (MARD 38.8%) leading to a failure to detect more than half of
      the true hypoglycaemic events (sensitivity 37.5%). Furthermore, more than half of
      the alarms that warn patients for hypoglycaemia were false (false alert rate
      53.3%). Above the low alert threshold, the sensor confirmed 2077 of 2182
      reference values (specificity 95.2%). CONCLUSIONS: Patients using continuous
      glucose monitoring should be aware of its limitation to accurately detect
      hypoglycaemia.

PMID- 22974232
TI  - Hepatocyte growth factor in the neighborhood reverses resistance to BRAF
      inhibitor in melanoma.

PMID- 22974234
TI  - Structural and nanomechanical properties of paperboard coatings studied by peak
      force tapping atomic force microscopy.
AB  - Paper coating formulations containing starch, latex, and clay were applied to
      paperboard and have been investigated by scanning electron microscopy and Peak
      Force tapping atomic force microscopy.  A special focus has been on the
      measurement of the variation of the surface topography and surface material
      properties with a nanometer scaled spatial resolution. The effects of coating
      composition and drying conditions were investigated. It is concluded that the air
      coating interface of the coating is dominated by close-packed latex particles
      embedded in a starch matrix and that the spatial distribution of the different
      components in the coating can be identified due to their variation in material
      properties. Drying the coating at an elevated temperature compared to room
      temperature changes the surface morphology and the surface material properties
      due to partial film formation of latex. However, it is evident that the chosen
      elevated drying temperature and exposure time is insufficient to ensure complete
      film formation of the latex which in an end application will be needed.

PMID- 22974233
TI  - Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and
      cathepsin K.
AB  - BACKGROUND: Coronins are a family of highly evolutionary conserved proteins
      reportedly involved in the regulation of actin cytoskeletal dynamics, although
      only coronin 3 has been shown to be related to cancer cell migration. In
      glioblastoma cells, the knockdown of coronin 3 inhibits cell proliferation and
      invasion. Coronin 3 is also associated with the aggression and metastasis of
      hepatocellular carcinoma. In this paper, we analyze the migration, invasion and
      metastasis abilities of gastric cancer cells after up- or down-regulation of
      coronin 3, and explore the mechanism of coronin 3 in the process of gastric
      cancer metastasis. RESULTS: The expression of coronin 3 was higher in the highly
      metastatic sub-cell line MKN28-M, which we established in our laboratory. We also
      demonstrated that the expression of coronin 3 was remarkably higher in lymph lode
      metastases than in primary gastric cancer tissues, and over-expression of coronin
      3 was correlated with the increased clinical stage and lymph lode metastasis.
      Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate
      coronin 3 expression in gastric cancer cell lines. Stable knockdown of coronin 3
      by this lentiviral vector could efficiently inhibit the migration and invasion of
      MKN45 gastric cancer cells. In contrast, up-regulation of coronin 3 significantly
      enhanced migration and invasion of MKN28-NM cells. In addition, knockdown of
      coronin 3 significantly reduced liver metastasis in mice after tail vein
      injection of gastric cancer cells. The Human Tumor Metastasis PCR Array was used
      to screen the metastasis-associated genes identified by the down-regulation of
      coronin 3, and the results suggested that, following the knockdown of coronin 3,
      the tumor cell migration and invasion were inhibited by the reduced expression of
      MMP-9 and cathepsin K. CONCLUSION: Coronin 3 is highly expressed in gastric
      cancer metastases and can promote the metastatic behaviors of gastric cancer
      cells, including their migration and invasion.

PMID- 22974235
TI  - A survey of visually induced symptoms and associated factors in spectators of
      three dimensional stereoscopic movies.
AB  - BACKGROUND: The increasing popularity of commercial movies showing three
      dimensional (3D) computer generated images has raised concern about image safety
      and possible side effects on population health.This study aims to (1) quantify
      the occurrence of visually induced symptoms suffered by the spectators during and
      after viewing a commercial 3D movie and (2) to assess individual and
      environmental factors associated to those symptoms. METHODS: A cross-sectional
      survey was carried out using a paper based, self administered questionnaire. The
      questionnaire includes individual and movie characteristics and selected visually
      induced symptoms (tired eyes, double vision, headache, dizziness, nausea and
      palpitations). Symptoms were queried at 3 different times: during, right after
      and after 2 hours from the movie. RESULTS: We collected 953 questionnaires. In
      our sample, 539 (60.4%) individuals reported 1 or more symptoms during the movie,
      392 (43.2%) right after and 139 (15.3%) at 2 hours from the movie. The most
      frequently reported symptoms were tired eyes (during the movie by 34.8%, right
      after by 24.0%, after 2 hours by 5.7% of individuals) and headache (during the
      movie by 13.7%, right after by 16.8%, after 2 hours by 8.3% of individuals).
      Individual history for frequent headache was associated with tired eyes (OR =
      1.34, 95%CI = 1.01-1.79), double vision (OR = 1.96; 95%CI = 1.13-3.41), headache
      (OR = 2.09; 95%CI = 1.41-3.10) during the movie and of headache after the movie
      (OR = 1.64; 95%CI = 1.16-2.32). Individual susceptibility to car sickness,
      dizziness, anxiety level, movie show time, animation 3D movie were also
      associated to several other symptoms. CONCLUSIONS: The high occurrence of
      visually induced symptoms resulting from this survey suggests the need of raising
      public awareness on possible discomfort that susceptible individuals may suffer
      during and after the vision of 3D movies.

PMID- 22974236
TI  - Musical learning in children and adults with Williams syndrome.
AB  - BACKGROUND: There is recent interest in using music making as an empirically
      supported intervention for various neurodevelopmental disorders due to music's
      engagement of perceptual-motor mapping processes. However, little is known about
      music learning in populations with developmental disabilities. Williams syndrome
      (WS) is a neurodevelopmental genetic disorder whose characteristic auditory
      strengths and visual-spatial weaknesses map onto the processes used to learn to
      play a musical instrument. METHODS: We identified correlates of novel musical
      instrument learning in WS by teaching 46 children and adults (7-49 years) with WS
      to play the Appalachian dulcimer. RESULTS: Obtained dulcimer skill was associated
      with prior musical abilities (r = 0.634, P < 0.001) and visual-motor integration
      abilities (r = 0.487, P = 0.001), but not age, gender, IQ, handedness, auditory
      sensitivities or musical interest/emotionality. Use of auditory learning
      strategies, but not visual or instructional strategies, predicted greater
      dulcimer skill beyond individual musical and visual-motor integration abilities
      (beta = 0.285, sr(2) = 0.06, P = 0.019). CONCLUSIONS: These findings map onto
      behavioural and emerging neural evidence for greater auditory-motor mapping
      processes in WS. Results suggest that explicit awareness of task-specific
      learning approaches is important when learning a new skill. Implications for
      using music with populations with syndrome-specific strengths and weakness will
      be discussed.

PMID- 22974238
TI  - Chromosome translocation, B cell lymphoma, and activation-induced cytidine
      deaminase.
AB  - Studies of B cell lymphomas in the early 1980s led to the cloning of genes (c-MYC
      and IGH) at a chromosome translocation breakpoint. A rush followed to identify
      recurrently translocated genes in all types of cancer, which led to remarkable
      advances in our understanding of cancer genetics. B lymphocyte tumors commonly
      bear chromosome translocations to immunoglobulin genes, which points to a role
      for antibody gene diversification processes in tumorigenesis. The discovery of
      activation-induced cytidine deaminase (AID) and the use of murine models to study
      translocation have led to a new understanding of how these events contribute to
      the genesis of lymphomas. Here, we review these advances with a focus on AID and
      insights gained from the study of translocations in primary cells.

PMID- 22974237
TI  - Influenza virus-membrane fusion triggered by proton uncaging for single particle
      studies of fusion kinetics.
AB  - We report a method for studying membrane fusion, focusing on influenza virus
      fusion to lipid bilayers, which provides high temporal resolution through the
      rapid and coordinated initiation of individual virus fusion events. Each fusion
      event proceeds through a series of steps, much like multistep chemical reaction.
      Fusion is initiated by a rapid decrease in pH that accompanies the "uncaging" of
      an effector molecule from o-nitrobenzaldehyde, a photoisomerizable compound that
      releases a proton to the surrounding solution within microseconds of long-wave
      ultraviolet irradiation. In order to quantify pH values upon UV irradiation and
      uncaging, we introduce a simple silica nanoparticle pH sensor, useful for
      reporting the pH in homogeneous nanoliter volumes under conditions where
      traditional organic dye-type pH probes fail. Subsequent single-virion fusion
      events are monitored using total internal reflection fluorescence microscopy.
      Statistical analysis of these stochastic events uncovers kinetic information
      about the fusion reaction. This approach reveals that the kinetic parameters
      obtained from the data are sensitive to the rate at which protons are delivered
      to the bound viruses. Higher resolution measurements can enhance fundamental
      fusion studies and aid antiviral antifusogenic drug development.

PMID- 22974239
TI  - The functional comorbidity index had high inter-rater reliability in patients
      with acute lung injury.
AB  - BACKGROUND: The Functional Comorbidity Index (FCI) was recently developed to
      predict physical function in acute lung injury patients using comorbidity data.
      Our objectives were to determine: (1) the inter-rater reliability of the FCI
      collected using in-patient discharge summaries (primary objective); and (2) the
      accuracy and predictive validity of the FCI collected using hospital discharge
      summaries and admission records versus complete chart review (secondary
      objectives). METHODS: For reliability, we evaluated the FCI's intraclass
      correlation coefficient (ICC) among trained research staff performing data
      collection for 421 acute lung injury patients enrolled in a prospective cohort
      study. For validity and accuracy, we compared the detection of FCI comorbidities
      across three types of inpatient medical records, and the association of the
      respective FCI scores obtained with patients' SF-36 physical function subscale
      (PFS) scores at 1-year follow-up. RESULTS: Inter-rater reliability was near
      perfect (ICC 0.91; 95% CI 0.89-0.94). Hospital admission records and discharge
      summaries (vs. complete chart review) significantly underestimated the total FCI
      score. However, using multivariable linear regression, FCI scores collected using
      each of the three types of inpatient medical records had similar associations
      with PFS, suggesting similar predictive value. CONCLUSIONS: Data collection using
      in-patient discharge summaries represents a reliable and valid method for
      collecting FCI comorbidity information.

PMID- 22974241
TI  - Electron attachment to Fe(CO)n (n = 0-5).
AB  - The rate constants of thermal electron attachment at 300 and 400 K to Fe(CO)(n)
      (n = 0-5) have been measured using a flowing afterglow Langmuir probe apparatus.
      The stable species Fe(CO)(5) was studied using the traditional method of
      monitoring electron depletion as a function of reaction time, and the remaining
      short-lived species were studied using the variable electron and neutral density
      attachment mass spectrometry (VENDAMS) technique. Attachment to Fe(CO)(5) is
      purely dissociative and about 20% efficient with a rate constant of (7.9 +/- 1.4)
      * 10(-8) cm(3) s(-1) at 300 K and (8.8 +/- 2) * 10(-8) cm(3) s(-1) at 400 K. The
      attachment rate constants decrease significantly as each CO ligand is removed,
      with Fe(CO)(n) (n = 4 to 1) attaching with efficiencies on the order of 10%, 1%,
      0.1%, and 0.01% respectively. Under the conditions here, attachment to Fe(CO)(4)
      and Fe(CO)(3) are likely entirely dissociative, whereas attachment to Fe(CO)(2)
      and Fe(CO) are almost entirely associative. A statistical kinetic modeling
      approach is used to explain the strong dependence of the attachment rate constant
      on the number of ligands present in the neutral species through a combination of
      increasing autodetachment rates and decreasing exothermicities to dissociative
      attachment. The VENDAMS data also define the 300 K mutual neutralization rate
      constant of Fe(CO)(4)(-) + Ar(+) to be (5.0 +/- 0.8) * 10(-8) cm(3) s(-1) with an
      upper limit to branching fraction of 0.5 to yield Fe(CO)(4), indicating that
      significant fragmentation to smaller Fe(CO)(n) occurs.

PMID- 22974240
TI  - Cochlear implant rehabilitation in older adults: literature review and proposal
      of a conceptual framework.
AB  - OBJECTIVES: To review studies investigating cochlear implant (CI) outcomes in
      older adults, and to develop a conceptual framework demonstrating important
      interactions between characteristics of hearing disability, aging, and the CI
      intervention. DESIGN: Review of English literature with titles containing the
      words "cochlear implant" and generic term referring to older adults or numerical
      value for age greater than 65. RESULTS: Hearing loss is a prevalent consequence
      of aging and poses special challenges for older adults. Particularly when
      superimposed on other age-related conditions, presbycusis (age-related hearing
      loss) places older adults at risk for social isolation and associated
      psychological and general health sequelae. The increasing cognitive demand of
      verbal communication and the diminished sense of social and physical
      connectedness can contribute to a feeling of vulnerability and poor health that
      worsens with advancing presbycusis. This cascade of downstream effects of hearing
      loss has implications for the self-assessment of health-related quality of life
      (HRQoL) and resulting estimates of associated costs. There is accumulating
      evidence of a potential role for CI in older adults with poor word understanding
      despite conventional hearing aid use. This review of the literature provides
      strong evidence of the benefits of restoring communication capacity in the deaf
      and hard-of-hearing geriatric population. There is, however, a lack of attention
      to communication performance in the real world and HRQoL outcomes, and
      significant gaps in knowledge regarding how CI rehabilitation interacts with
      changing psychosocial and functional status with aging. CONCLUSION: A broader
      conceptual framework than is currently available for the role of CI
      rehabilitation in the management of severe-to-profound hearing loss in older
      adults is proposed. It is posited that the use of such a model in future
      investigations is needed to guide multidisciplinary investigations into the
      unique challenges of hearing loss in older adults and may open new opportunities
      for innovation.

PMID- 22974242
TI  - Demographics and economic burden of un-owned cats and dogs in the UK: results of
      a 2010 census.
AB  - BACKGROUND: The population of dogs and cats passing through rescue shelters may
      be subject to compromised welfare and increased susceptibility to disease. Little
      information exists to describe this population, its dynamics and associated
      management practices. The aim of this study was to carry out a census of un-owned
      cats and dogs in the UK in 2010, and to document the origins, destinations,
      husbandry and costs associated with the care of these animals. RESULTS: A
      sampling frame was constructed by searching the databases of publicly registered
      charities for England, Scotland and Wales, registers of breed rescues, and by
      internet searches of animal welfare websites. Overall, 2,352 contacts for 1,380
      organisations were identified. All were sent a postal questionnaire asking for
      data on the number of dogs and cats housed, their origins and eventual outcomes,
      and details of husbandry between January 1st and December 31st 2010. For those
      which were registered charities (595), financial records were also obtained.A
      response rate of 38.8% was obtained. Overall, in 2010, 89,571 dogs and 156,826
      cats entered the care of the participating organisations. Approximately half of
      these animals were relinquished by their owners. Other origins included being
      found as strays or confiscated for welfare purposes. Seventy-five per cent of
      dogs and 77.1% of cats were rehomed. The next most common outcome was euthanasia,
      accounting for 10.4% of dogs and 13.2% cats. For dogs and cats, 44.3% and 62% of
      participants respectively reported having a waiting list, which frequently
      exceeded the actual capacity of the facility. Over 19,000 people were involved in
      the care of these animals, on a paid or voluntary basis. Financial records were
      available for 519/595 (87.2%) of the registered charities, and their total
      expenditure in 2010 was L340 million. CONCLUSIONS: This study showed that a large
      number of animals become un-owned each year, which could have considerable
      implications for their welfare. Despite the resources expended, demand still
      exceeds capacity for many organisations, and a substantial number of both cats
      and dogs are euthanased, suggesting that further understanding of how and why
      these animals become un-owned is essential in order to target interventions.

PMID- 22974243
TI  - Comparison of filtering methods for extracellular gastric slow wave recordings.
AB  - BACKGROUND: Extracellular recordings are used to define gastric slow wave
      propagation. Signal filtering is a key step in the analysis and interpretation of
      extracellular slow wave data; however, there is controversy and uncertainty
      regarding the appropriate filtering settings. This study investigated the effect
      of various standard filters on the morphology and measurement of extracellular
      gastric slow waves. METHODS: Experimental extracellular gastric slow waves were
      recorded from the serosal surface of the stomach from pigs and humans. Four
      digital filters: finite impulse response filter (0.05-1 Hz); Savitzky-Golay
      filter (0-1.98 Hz); Bessel filter (2-100 Hz); and Butterworth filter (5-100 Hz);
      were applied on extracellular gastric slow wave signals to compare the changes
      temporally (morphology of the signal) and spectrally (signals in the frequency
      domain). KEY RESULTS: The extracellular slow wave activity is represented in the
      frequency domain by a dominant frequency and its associated harmonics in
      diminishing power. Optimal filters apply cutoff frequencies consistent with the
      dominant slow wave frequency (3-5 cpm) and main harmonics (up to ~ 2 Hz).
      Applying filters with cutoff frequencies above or below the dominant and harmonic
      frequencies was found to distort or eliminate slow wave signal content.
      CONCLUSIONS & INFERENCES: Investigators must be cognizant of these optimal
      filtering practices when detecting, analyzing, and interpreting extracellular
      slow wave recordings. The use of frequency domain analysis is important for
      identifying the dominant and harmonics of the signal of interest. Capturing the
      dominant frequency and major harmonics of slow wave is crucial for accurate
      representation of slow wave activity in the time domain. Standardized filter
      settings should be determined.

PMID- 22974244
TI  - Renal allograft recipients fail to increase interferon-gamma during invasive
      fungal diseases.
AB  - Invasive fungal diseases are a major cause of death in renal allograft
      recipients. We previously reported that adjunctive recombinant human interferon
      gamma therapy has clinical utility for invasive fungal diseases after renal
      transplantation. We have now developed a rapid peripheral blood-based
      quantitative real-time PCR assay that enables accurate profiling of cytokine
      imbalances. Our preliminary studies in renal transplant patients with invasive
      fungal diseases suggest that they fail to mount an adequate interferon-gamma
      response to the fungal infection. In addition, they have reduced IL-10 and
      increased TNF-alpha when compared to stable renal transplant patients. These
      preliminary cytokine profiling-based observations provide a possible explanation
      for the therapeutic benefit of adjunctive human interferon-gamma therapy in renal
      allograft recipients with invasive fungal diseases.

PMID- 22974245
TI  - Disseminated herpes simplex virus type-1 infection in long-term usage of
      everolimus.

PMID- 22974246
TI  - Meshless algorithm for soft tissue cutting in surgical simulation.
AB  - Computation of soft tissue mechanical responses for surgery simulation and image
      guided surgery has been dominated by the finite element (FE) method that utilises
      a mesh of interconnected elements as a computational grid. Shortcomings of such
      mesh-based discretisation in modelling of surgical cutting include high
      computational cost and the need for re-meshing in the vicinity of cutting-induced
      discontinuity. The meshless total Lagrangian adaptive dynamic relaxation (MTLADR)
      algorithm we present here does not exhibit such shortcomings, as it relies on
      spatial discretisation in a form of a cloud of nodes. The cutting-induced
      discontinuity is modelled solely through changes in nodal domains of influence,
      which is done through efficient implementation of the visibility criterion using
      the level set method. Accuracy of our MTLADR algorithm with visibility criterion
      is confirmed against the established nonlinear solution procedures available in
      the commercial FE code Abaqus. 

PMID- 22974247
TI  - Inflammasomes and their roles in health and disease.
AB  - Inflammasomes are a set of intracellular protein complexes that enable
      autocatalytic activation of inflammatory caspases, which drive host and immune
      responses by releasing cytokines and alarmins into circulation and by inducing
      pyroptosis, a proinflammatory cell death mode. The inflammasome type mediating
      these responses varies with the microbial pathogen or stress factor that poses a
      threat to the organism. Since the discovery that polymorphisms in inflammasome
      genes are linked to common autoimmune diseases and less frequent periodic fever
      syndromes, inflammasome signaling has been dissected at the molecular level. In
      this review, we present recently gained insight on the distinct inflammasome
      types, their activation and effector mechanisms, and their modulation by
      microbial virulence factors. In addition, we discuss recently gained knowledge on
      the role of deregulated inflammasome activity in human autoinflammatory,
      autoimmune, and infectious diseases.

PMID- 22974248
TI  - The specialising or sampling debate: a retrospective analysis of adolescent
      sports participation in the UK.
AB  - Whether young people should specialise in one competitive sport at an early age,
      or pursue a wider range of sports during adolescence is a topic of some debate
      (Baker, Cobley, & Fraser-Thomas, 2009) and is fundamental within sports policy
      and coaching practice. The purpose of this retrospective recall study was to
      identify whether early specialisation or sporting diversification (sampling)
      throughout childhood and adolescence can influence performance levels prior to
      adulthood. An online questionnaire was used to collect the sport participation
      histories of 1006 UK sports people, which were then compared with the
      developmental framework provided by the Developmental Model of Sport
      Participation (DMSP, Cote & Fraser-Thomas, 2007). A significant association
      between the number of sports participated in at the ages of 11, 13, and 15 and
      the standard of competition between 16 and 18 years was found. Individuals who
      competed in three sports aged 11, 13, and 15 were significantly more likely to
      compete at a national compared with club standard between the ages of 16 and 18
      than those who practised only one sport. The findings reported here provide some
      empirical support for the sampling performance pathway DMSP model in a UK
      context.

PMID- 22974249
TI  - Cardioselective beta-blocker treatment of hypertension in patients with asthma:
      when do benefits outweigh risks?
AB  - BACKGROUND: Benefits outweigh risks of cardioselective beta-blocker therapy in
      patients with nonsevere asthma and a history of heart failure or myocardial
      infarction (MI). This review summarizes the risks versus benefits of using
      cardioselective beta-blockers in the treatment of hypertension in patients with
      asthma. METHODS: We searched the English literature from 1976 to 2011 via PubMed,
      EMBASE, and SCOPUS using the following search terms: "beta-blocker treatment of
      hypertension" AND "asthma"; "cardioselective beta-blockers" AND "asthma." When
      pertinent articles were found, we assessed relevant articles cited in those
      papers. All studies related to cardioselective beta-blocker use in patients with
      asthma and hypertension were included. RESULTS: Seven studies with patient
      populations ranging from 10 to 17 patients evaluated cardioselective beta
      blockers in patients with asthma and hypertension. Atenolol and/or immediate
      release metoprolol were evaluated in these studies. The duration of beta-blocker
      therapy in four studies was 1-8 weeks; two studies were single dose and one
      investigation lasted 8 months. Metoprolol and atenolol were generally well
      tolerated except at higher doses such as metoprolol >100 mg daily. CONCLUSION: In
      the absence of concomitant cardiovascular disease, routine use of beta-blockers
      for the treatment of hypertension in patients with asthma should be avoided.

PMID- 22974250
TI  - Understanding the forces that govern packing: a density functional theory and
      structural investigation of anion-pi-anion and nonclassical C-H...anion
      interactions.
AB  - The ability of Ni(II) coordinated 4-pyrrolyl-3,5-di(2-pyridyl)-1,2,4-triazole
      (pldpt) to establish multiple anion-pi interactions is analyzed. Experimentally,
      such complexes were previously shown to form strong anion-pi interactions,
      including "pi-pocket" and "pi-sandwiched" motifs, in the crystal lattice. In the
      latter, the triazole ring is "sandwiched" by two anions forming a ternary anion
      pi-anion assembly (pi-sandwich) which, surprisingly, gave about 0.2 A shorter
      anion-pi distances than in binary assemblies (where only one side of the triazole
      participates in the anion binding), indicating the possibility of cooperativity.
      In depth analysis, using dispersion-corrected density functional theory (DFT,
      BP86-D/def2-TZVP level of theory), shows that this ternary anion-pi-anion
      interaction is slightly less energetically favorable than the binary anion-pi
      interactions in isolation. Hence, the sandwich interaction is not cooperative
      (E(coop) is positive), but, as E(coop) contributes less than 1.5% of the total
      interaction energy (which is dominated by the strong electrostatic attraction of
      the anions to the highly pi-acidic Ni(II)-coordinated triazole ring), the
      presence of nonclassical C-H...anion hydrogen bonds can offset this, making the
      short anion-pi sandwich interactions the most favorable solid state conformation.

PMID- 22974251
TI  - Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal
      human adipose tissue.
AB  - BACKGROUND: Inflammation and increased ceramide concentrations characterise
      adipose tissue of obese women with high liver fat content compared to equally
      obese women with normal liver fat content. The present study characterises
      enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal
      adipose tissue. METHODS: Pathways leading to increased ceramide concentrations in
      inflamed versus non-inflamed adipose tissue were investigated by quantifying
      expression levels of key enzymes involved in ceramide metabolism.
      Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated
      further using immunohistochemistry to establish their location within adipose
      tissue, and their mRNA expression levels were determined in subcutaneous and
      intra-abdominal adipose tissue from both non-obese and obese subject. RESULTS:
      Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin
      to ceramide, rather than enzymes involved in de novo ceramide synthesis, were
      higher in inflamed compared to non-inflamed adipose tissue of obese women (with
      high and normal liver fat contents respectively). Sphingomyelinases were
      localised to both macrophages and adipocytes, but also to blood vessels and to
      extracellular regions surrounding vessels within adipose tissue. Expression
      levels of SMPD3 mRNA correlated significantly with concentrations of different
      ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA
      levels were higher in the more inflamed intra-abdominal compared to the
      subcutaneous adipose tissue depot. CONCLUSIONS: Generation of ceramides within
      adipose tissue as a result of sphingomyelinase action may contribute to
      inflammation in human adipose tissue.

PMID- 22974252
TI  - Novel approach for deriving genome wide SNP analysis data from archived blood
      spots.
AB  - BACKGROUND: The ability to transport and store DNA at room temperature in low
      volumes has the advantage of optimising cost, time and storage space. Blood spots
      on adapted filter papers are popular for this, with FTA (Flinders Technology
      Associates) WhatmanTMTM technology being one of the most recent. Plant material,
      plasmids, viral particles, bacteria and animal blood have been stored and
      transported successfully using this technology, however the method of porcine DNA
      extraction from FTA WhatmanTMTM cards is a relatively new approach, allowing
      nucleic acids to be ready for downstream applications such as PCR, whole genome
      amplification, sequencing and subsequent application to single nucleotide
      polymorphism microarrays has hitherto been under-explored. FINDINGS: DNA was
      extracted from FTA WhatmanTMTM cards (following adaptations of the manufacturer's
      instructions), whole genome amplified and subsequently analysed to validate the
      integrity of the DNA for downstream SNP analysis. DNA was successfully extracted
      from 288/288 samples and amplified by WGA. Allele dropout post WGA, was observed
      in less than 2% of samples and there was no clear evidence of amplification bias
      nor contamination. Acceptable call rates on porcine SNP chips were also achieved
      using DNA extracted and amplified in this way. CONCLUSIONS: DNA extracted from
      FTA Whatman cards is of a high enough quality and quantity following whole
      genomic amplification to perform meaningful SNP chip studies.

PMID- 22974254
TI  - The effect of oral prostaglandin analogue on painful diabetic neuropathy: a
      double-blind, randomized, controlled trial.
AB  - This study was performed to assess the efficacy of beraprost sodium (BPS) in
      painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM)
      patients. In this randomized clinical trial, 99 T2DM patients (41% male, age 60
      +/- 6 years) with DPN but without evidence of peripheral artery disease were
      randomized to receive either BPS (40 ug, tid) or placebo for 8 weeks. The primary
      end point was the improvement of the total symptom score (TSS), temperature
      rebound (TR) and nadir to peak (NP) above baseline. After 8 weeks treatment, the
      change of TSS in the BPS group showed a significant improvement compared to the
      placebo group (2.80 +/- 2.48 vs. 1.60 +/- 1.94 points, p = 0.009). Furthermore,
      the number of patients who showed signs of improvement in TSS and the proportion
      of patients with 50% relief of symptom was also significantly greater in the BPS
      group than in the placebo group (83.7 vs. 62%, p = 0.015, 36.2 vs. 14%, p =
      0.009, respectively). In conclusion, treatment with BPS significantly improved
      TSS over an 8-week period.

PMID- 22974255
TI  - Solid lipid nanoparticles (SLNs) for topical delivery of aceclofenac by using
      xanthan  gum: Ex vivo and in vivo evaluation.
AB  - Solid lipid nanoparticles (SLN) are very potential formulations for topical
      delivery of anti-inflammatory and anti-arthritic drugs. The solid state of the
      lipid particle enables efficient drug encapsulation and controlled drug release.
      In the present study the evaluation of different parameters based on variation of
      concentration of lipid and co-surfactant was studied. The SLN gel formulation of
      the same dispersion was compared with the SLN dispersion and with the marketed
      gel formulation of aceclofenac. At first the solid lipid nanoparticles were
      prepared by high speed homogenization and ultra-sonication method with fixed
      amount of aceclofenac (10%) and pluronic F68 (1.5%). The particle size, zeta
      potential and span was found to be within the range of 123 nm to 323 nm, -12.4 to
      -18.5 and 0.42 to 0.86 respectively as the lipid concentration was increasing
      from 7.5% to 40%. The highest entrapment efficiency was found to be 75% with the
      formulation having lipid concentration of 30% and 0.85% of phospholipon 90G
      (Phospholipid as co-surfactant). Particle surface morphology was measured by
      scanning electron microscope (SEM). Permeation rate and controlled release
      property of xanthan gum loaded SLN gel formulations and SLN dispersion was
      studied through the excised pig skin for 24hr and it was found that release rate
      of SLN gel formulation was more controlled as compare to SLN dispersions. In vivo
      pharmacodynamic study was carried out for 24 hr by injecting 0.1ml (w/v) CFA
      (Complete Fraud's Adjuvant). From the in vitro and in vivo study it was found
      that action of aceclofenac was enhanced by prepared SLN dispersion and gel
      formulations. The results indicated the utility of both SLN dispersion and SLN
      gel system for transdermal delivery of aceclofenac as excellent and logical.

PMID- 22974253
TI  - Further development of a neurobehavioral profile of fetal alcohol spectrum
      disorders.
AB  - BACKGROUND: Heavy prenatal alcohol exposure (AE) results in a broad array of
      neurobehavioral deficits. Recent research has focused on identification of a
      neurobehavioral profile or profiles that will improve the identification of
      children affected by AE. This study aimed to build on our preliminary
      neurobehavioral profile to improve classification accuracy and test the
      specificity of the resulting profile in an alternate clinical group. METHODS: A
      standardized neuropsychological test battery was administered to 3 groups of
      children: subjects with AE (n = 209), typically developing controls (CON, n =
      185), and subjects with attention-deficit/hyperactivity disorder (ADHD, n = 74).
      We assessed a large sample from 6 sites in the United States and South Africa,
      using standardized methodology. Data were analyzed using 3 latent profile
      analyses including (i) subjects with fetal alcohol syndrome (FAS) and controls,
      (ii) subjects with AE without FAS and controls, and (iii) subjects with AE (with
      or without FAS) and subjects with ADHD. RESULTS: Classification accuracy was
      moderate but significant across the 3 analyses. In analysis 1, overall
      classification accuracy was 76.1% (77.2% FAS, 75.7% CON). In the second analysis,
      overall classification accuracy was 71.5% (70.1% AE/non-FAS, 72.4% CON). In the
      third analysis, overall classification accuracy was 73.9% (59.8% AE, 75.7% ADHD).
      Subjects that were misclassified were examined for systematic differences from
      those that were correctly classified. CONCLUSIONS: The results of this study
      indicate that the neuropsychological effects of AE are clinically meaningful and
      can be used to accurately distinguish alcohol-affected children from both
      typically developing children and children with ADHD. Further, in combination
      with other recent studies, these data suggest that approximately 70% of children
      with heavy prenatal alcohol exposure are neurobehaviorally affected, while the
      remaining 30% are spared these often-devastating consequences, at least those in
      the domains under study. Refining the neurobehavioral profile will allow improved
      identification and treatment development for children affected by prenatal
      alcohol exposure.

PMID- 22974256
TI  - Missed and inconsistent classification of current drinkers: results from the 2005
      US National Alcohol Survey.
AB  - AIMS: This study compares current 12-month drinkers who do not report drinking in
      the last 30 days with current drinkers who drank in the last 30 days and assesses
      possible misclassification errors from use of a 30-day consumption measure.
      DESIGN: Data are from the 2005 US National Alcohol Survey (n = 6919), a national
      household probability survey. SETTING: Telephone interviews were used to measure
      alcohol use and alcohol-related problems. PARTICIPANTS: This study compared 1300
      current drinkers who did not drink in the last 30 days with 2956 current drinkers
      who drank in the last 30 days. MEASUREMENTS: Volume was measured by
      quantity/frequency scales (12-month and 30-day) and a graduated frequency scale
      (12-month). Both groups were compared by demographic, alcohol volume, days of
      five or more drinks, social consequences and dependence measures. FINDINGS:
      Results indicate a significantly lower prevalence rate of current drinking for 30
      day measures-47.3% (45.8%, 48.8%) versus 67.3% (66.0%, 68.7%) with 12-month
      measures. Further, 385 non-30-day drinkers reported 12-month drinking frequencies
      of once a month or more often, suggesting possible inconsistent reporting of
      their alcohol use. When this group of 'inconsistent' respondents is compared with
      the 915 non-30-day current drinkers who reported less than monthly drinking, they
      reported significantly higher yearly volume, days of five or more drinks, mean
      social consequences and proportion reporting alcohol dependence. CONCLUSIONS: In
      population surveys assessing alcohol use, asking about the previous 12 months
      rather than the past 30 days provides higher estimates of current use, including
      more days of heavy episodic use.

PMID- 22974258
TI  - GapMis: a tool for pairwise sequence alignment with a single gap.
AB  - MOTIVATION: Pairwise sequence alignment has received a new motivation due to the
      advent of recent patents in next-generation sequencing technologies, particularly
      so for the application of re-sequencing---the assembly of a genome directed by a
      reference sequence. After the fast alignment between a factor of the reference
      sequence and a high-quality fragment of a short read by a short-read alignment
      programme, an important problem is to find the alignment between a relatively
      short succeeding factor of the reference sequence and the remaining low-quality
      part of the read allowing a number of mismatches and the insertion of a single
      gap in the alignment. RESULTS: We present GapMis, a tool for pairwise sequence
      alignment with a single gap. It is based on a simple algorithm, which computes a
      different version of the traditional dynamic programming matrix. The presented
      experimental results demonstrate that GapMis is more suitable and efficient than
      most popular tools for this task.

PMID- 22974257
TI  - "Psychosomatic consultation in the workplace": a new model of care at the
      interface of company-supported mental health care and consultation-liaison
      psychosomatics: design of a mixed methods implementation study.
AB  - BACKGROUND: Mental health issues are gaining in importance in society and the
      economic system. At the same time, the accessibility and stigmatisation of the
      mental health care system in Germany can obstruct help-seeking behavior and delay
      early psychotherapeutic interventions. Therefore, new models of care are being
      established at the interface of company-supported health promotion and
      conventional health insurance sponsored outpatient care for people developing
      mental illnesses. Two large industrial companies, in cooperation with two
      psychosomatic clinics, have recently established a model of "psychosomatic
      consultation in the workplace". This new model of care offers the opportunity for
      a first psychotherapeutic door to door consultation with occupational medicine
      within the industrial workplace. The main empirical goals of this study are:1)
      Describing the differences between patients who use this new diagnostic and
      therapeutic offer within the industrial workplace vs. patients who visit a
      conventional regional outpatient clinic, especially in regard to symptom duration
      and severity, work ability, and demographic characteristics, and2) A first
      evaluation of how patients may benefit more from this new model of care compared
      to those first seen by standard outpatient care.In the qualitative part of the
      study, occupational physicians, psychosomatic therapists, involved personnel and
      select employees of the involved companies will be asked to comment on their
      experiences with this new approach. METHODS/DESIGN: The implementation study will
      take place in Ulm and in Stuttgart, with each site looking at one regional
      conventional psychosomatic outpatient clinic and one psychosomatic consultation
      offer within the workplace. 70 consecutive patients in each setting will be
      recruited (overall n = 280). For the cross-sectional study and pre-post
      comparison we will use established and validated survey instruments (PHQ, SF-12,
      WAI, MBI, IS) as well as standardized questions about health care use. For data
      analysis, we will use uni- and multivariate analytical methods. Qualitative data
      analysis (expert interviews) will be carried out using Mayring's content analysis
      method. DISCUSSION: The results of this study have the potential to provide
      evidence-based knowledge about an innovative model of psychotherapeutic
      outpatient care and to further promote tailored solutions for early
      psychotherapeutic interventions within the worksite. TRIAL REGISTRATION:
      DRKS00003184.

PMID- 22974259
TI  - Pattern matching in indeterminate and Arc-annotated sequences.
AB  - In this paper, we present efficient algorithms for finding indeterminate Arc
      Annotated patterns in indeterminate Arc-Annotated references. Our algorithms run
      in O(m+ (nm) w) time where n and m are respectively the length of our reference
      and pattern strings and w is the target machine word size. Here we have assumed
      the alphabet size to be constant, because, indeterminate Arc-Annotated sequences
      are used to model biological sequences. Clearly, for short patterns, our
      algorithms run in linear time and efficient algorithms for matching short
      patterns to reference genomes have huge applications in practical settings. We
      have also applied our algorithms to scan the ncRNAs without pseudoknots. We
      scanned three whole human chromosomes and it took only 2.5 - 4 minutes to scan
      one whole chromosome for an ncRNA family. Some relevant patents are discussed in.

PMID- 22974260
TI  - Genetic algorithms with permutation coding for multiple sequence alignment.
AB  - Multiple sequence alignment (MSA) is one of the topics of bio informatics that
      has seriously been researched. It is known as NP-complete problem. It is also
      considered as one of the most important and daunting tasks in computational
      biology. Concerning this a wide number of heuristic algorithms have been proposed
      to find optimal alignment. Among these heuristic algorithms are genetic
      algorithms (GA). The GA has mainly two major weaknesses: it is time consuming and
      can cause local minima. One of the significant aspects in the GA process in MSA
      is to maximize the similarities between sequences by adding and shuffling the
      gaps of Solution Coding (SC). Several ways for SC have been introduced. One of
      them is the Permutation Coding (PC). We propose a hybrid algorithm based on
      genetic algorithms (GAs) with a PC and 2-opt algorithm. The PC helps to code the
      MSA solution which maximizes the gain of resources, reliability and diversity of
      GA. The use of the PC opens the area by applying all functions over permutations
      for MSA. Thus, we suggest an algorithm to calculate the scoring function for
      multiple alignments based on PC, which is used as fitness function. The time
      complexity of the GA is reduced by using this algorithm. Our GA is implemented
      with different selections strategies and different crossovers. The probability of
      crossover and mutation is set as one strategy. Relevant patents have been probed
      in the topic.

PMID- 22974261
TI  - A computational approach to finding RNA tertiary motifs in genomic sequences: a
      case study.
AB  - Motif finding in DNA, RNA and proteins plays an important role in life science
      research. Recent patents concerning motif finding in biomolecular data are
      recorded in the DNA Patent Database which serves as a resource for policy makers
      and members of the general public interested in fields like genomics, genetics
      and biotechnology. In this paper, we present a computational approach to mining
      for RNA tertiary motifs in genomic sequences. Specifically, we describe a method,
      named CSminer, and show, as a case study, the application of CSminer to genome
      wide search for coaxial helical stackings in RNA 3-way junctions. A coaxial
      helical stacking occurs in an RNA 3-way junction where two separate helical
      elements form a pseudocontiguous helix and provide thermodynamic stability to the
      RNA molecule as a whole. Experimental results demonstrate the effectiveness of
      our approach.

PMID- 22974262
TI  - Extraction of infrequent simple motifs from a finite set of sequences using a
      lattice structure.
AB  - In this paper we present a method for finding infrequent simple motifs in a
      finite set of sequences. The method uses a lattice structure and minimal
      forbidden patterns. It is based on a method for solving the Simple Motif Problem
      and has the potential to discover new patents in biological macromolecules.
      Indeed, the extracted motifs can help biologists to learn about the biological
      functions of these macromolecules and, consequently, can help them to understand
      the mechanisms of the biological processes in which these sequences are involved.

PMID- 22974263
TI  - Negative information for building phylogenies.
AB  - An absent word (also called a forbidden word or an unword in other contexts) in a
      sequence is a segment that does not appear in the given sequence. It is a minimal
      absent word if all its proper factors occur in the given sequence. In this
      article, we review the concept of minimal absent words, which includes the notion
      of shortest absent words but is much stronger. We present an efficient method for
      computing the minimal absent words of bounded length for DNA sequence using a
      Trie of bounded depth, representing bounded length factors. This method outputs
      the whole set of minimal absent words and furthermore our technique provides a
      linear-time algorithm with less memory usage than previous solutions. We also
      present an approach to distinguish sequences of different organisms using their
      minimal absent words. Our solution applies a length-weighted index to
      discriminate sequences and the results show that we can build phylogenetic tree
      based on the patent collected information.

PMID- 22974264
TI  - Rapid quantification of the activating effects of hydrogen-bonding catalysts with
      a colorimetric sensor.
AB  - A sensor has been developed to quickly and simply assess the relative reactivity
      of different hydrogen-bonding catalysts. Specifically, blue-shifts seen upon
      treatment of H-bonding catalysts with the colorimetric compound 7-methyl-2
      phenylimidazo[1,2-a]pyrazin-3(7H)-one correlate well to the K(eq) of binding to
      the sensor. The blue-shifts also show a high degree of correlation with relative
      rates in Diels-Alder reactions of methyl vinyl ketone and cyclopentadiene
      employing the H-bonding catalysts. The relevance of the sensor blue-shifts to the
      LUMO-lowering abilities of the H-bonding catalysts is discussed.

PMID- 22974265
TI  - Effect of the electrode materials on the drain-bias stress instabilities of In-Ga
      Zn-O thin-film transistors.
AB  - The effects of electrode materials on the device stabilities of In-Ga-Zn-O (IGZO)
      thin-film transistors (TFTs) were investigated under gate- and/or drain-bias
      stress conditions. The fabricated IGZO TFTs with a top-gate bottom-contact
      structure exhibited very similar transfer characteristics between the devices
      using indium-tin oxide (ITO) and titanium electrodes. Typical values of the
      mobility and threshold voltage of each device were obtained as 13.4 cm(2) V(-1)
      s(-1) and 0.72 V (ITO device) and 13.8 cm(2) V(-1) s(-1) and 0.66 V (titanium
      device). Even though the stabilities examined under negative and positive gate
      bias stresses showed no degradation for both devices, the instabilities caused by
      the drain-bias stress were significantly dependent on the types of electrode
      materials. The negative shifts of the threshold voltage for the ITO and titanium
      devices after the 10(4)-s-long drain-bias stress were estimated as 2.06 and 0.96
      V, respectively. Superior characteristics of the device using titanium electrodes
      after a higher temperature annealing process were suggested to originate from the
      formation of a self-limiting barrier layer at interfaces by nanoscale
      observations using transmission electron microscopy.

PMID- 22974266
TI  - Copper-catalyzed dehydrogenative cross-coupling of benzothiazoles with thiazoles
      and polyfluoroarene.
AB  - A copper-catalyzed dehydrogenative cross-coupling of benzothiazoles with
      thiazoles and polyfluoroarene under mild reaction conditions is described. This
      protocol provides a straightforward and operationally simple method for the
      synthesis of the 2,2'-linkage of thiazoles and 2-polyfluoroarylthiazoles of
      interest in life and material sciences.

PMID- 22974267
TI  - Influence of comorbidity in cancer surgery on treatment decisions, postoperative
      course and oncological outcome.
AB  - AIM: Comorbidity in cancer patients may influence treatment decisions,
      postoperative morbidity and ultimately, survival. The TNM staging system does not
      take comorbidity into account. This study investigates the burden of comorbidity
      in cancer patients, its effect on resection rate, postoperative morbidity,
      adjuvant therapy, recurrence and survival. METHODS:  This prospective cohort
      study included 358 patients with potentially operable cancer. Pretreatment
      comorbidity was assessed using a modified Kaplan-Feinstein index (adult
      comorbidity evaluation-27) and its influence on resection rate and postoperative
      adjuvant therapy was assessed. The comorbidity grade was consolidated with TNM
      stage into four distinct groups that were compared for differences in the
      incidence of postoperative complications, duration of hospital stay, 30-day
      mortality, recurrence and survival. RESULTS: Cardiovascular diseases including
      hypertension (27%) and diabetes mellitus (12%) were the most common
      comorbidities. Comorbidity did not influence the resection rate, but affected
      adjuvant treatment (P < 0.01). There was a greater incidence of postoperative
      local and systemic complications and duration of hospital stay in patients with
      comorbidity. Recurrence rates were unaffected. Mortality in patients with
      comorbidity was greater, especially postoperative 30-day mortality, but this was
      statistically insignificant. CONCLUSION: Comorbidity increases postoperative
      morbidity and affects adjuvant therapy, although the resection rate is not
      influenced. The greater percentage of deaths in patients with comorbidity
      warrants further studies. Recurrence rates remain unaffected. However, a longer
      period of follow up is needed for a clearer picture.

PMID- 22974269
TI  - Mitophagy or how to control the Jekyll and Hyde embedded in mitochondrial
      metabolism: implications for melanoma progression and drug resistance.
AB  - Proteins and pathways that control cell fate are placed under intense scrutiny.
      The same tight regulation applies to essential organelles that can both sustain
      cell survival or promote self-degradation programs. Mitochondria are perhaps the
      prime example of cellular machineries with split functions (personalities). As a
      main source of ATP, mitochondria represent the main powerhouse of eukaryotic
      cells. However, mitochondrial respiration has the hidden complication of the
      production of potentially harmful reactive oxygen species (ROS). Moreover,
      mitochondria holds an armamentarium of stress-response factors, which depending
      on the context, may lead to pro-inflammatory signals, and to various forms of
      cell death, ranging from apoptosis to necrosis. A main clearance mechanism to
      eliminate superfluous, damaged or hyperactive mitochondria is selective
      mitophagy. Mitophagy, in fact, is emerging as a key quality-control mechanism in
      cancer cells. Specifically, malignant transformation has been found to induce
      marked changes in mitochondrial dynamics and structure. Moreover, a key hallmark
      of tumor progression is metabolic reprogramming, which further deregulates ROS
      content and renders cells more susceptible to mitochondrial perturbations.
      Despite its increasing relevance in cancer biology, the field of mitophagy
      remains virtually unexplored in melanoma. However, given unique antioxidant
      mechanisms in melanocytic cells (e.g., linked to melanin) and the idiosyncratic
      interplay between ROS and hypoxia (both mitophagy inducers) in melanoma, this
      tumor type represents an ideal scenario for physiological studies of
      mitochondrial turnover. This perspective summarizes proof of concept for in-depth
      basic and translational studies of mitophagy in melanoma. Particular emphasis is
      dedicated to new opportunities for gene discovery and drug design in this still
      aggressive disease.

PMID- 22974268
TI  - Systems and cascades in cognitive development and academic achievement.
AB  - A large-scale (N = 552) controlled multivariate prospective 14-year longitudinal
      study of a developmental cascade embedded in a developmental system showed that
      information-processing efficiency in infancy (4 months), general mental
      development in toddlerhood (18 months), behavior difficulties in early childhood
      (36 months), psychometric intelligence in middle childhood (8 years), and
      maternal education either directly or indirectly (or both) contribute to academic
      achievement in adolescence (14 years).

PMID- 22974270
TI  - Surface effects on the crystallization of cyclo-1,3,5-trimethylene-2,4,6
      trinitramine (RDX) and the consequences for its N K X-ray emission spectrum.
AB  - Recent studies of the crystallization of cyclotrimethylene-trinitramine (RDX)
      have shown that the presence of the alpha- and beta-phases of the compound is
      sensitive to the substrate when using drop cast crystallization methods. The
      specific phase has potential consequences for measurements of the nitrogen K X
      ray emission spectrum (XES) that were recently reported for this compound using
      samples crystallized on In metal substrates. We have determined that the
      crystallization of RDX on a clean In metal substrate starts out completely as the
      beta-phase but progressively incorporates the alpha-phase as the film thickens.
      In addition, we have carried out additional molecular orbital calculations of the
      N 1s X-ray fluorescence from the valence band, comparing the results expected
      from the alpha-and beta- phases. The differences due to the presence of the beta
      phase instead of, or in addition to, the alpha-phase appear to be minimal.

PMID- 22974271
TI  - Fasting levels of ghrelin covary with the brain response to food pictures.
AB  - Ghrelin figures prominently in the regulation of appetite in normal-weighed
      individuals. The apparent failure of this mechanism in eating disorders and the
      connection to addictive behavior in general demand a deeper understanding of the
      endogenous central-nervous processes related to ghrelin. Thus, we investigated
      processing of pictures showing palatable food after overnight fasting and
      following a standardized caloric intake (i.e. a 75-g oral glucose tolerance test)
      using functional magnetic resonance imaging and correlated it with blood plasma
      levels of ghrelin. Twenty-six healthy female and male volunteers viewed food and
      control pictures in a block design and rated their appetite after each block.
      Fasting levels of ghrelin correlated positively with food-cue reactivity in a
      bilateral network of visual processing-, reward- and taste-related regions,
      including limbic and paralimbic regions. Notably, among those regions were the
      hypothalamus and the midbrain where ghrelin receptors are densely concentrated.
      In addition, high fasting ghrelin levels were associated with stronger increases
      of subjective appetite during the food-cue-reactivity task. In conclusion, brain
      activation and subjective appetite ratings suggest that ghrelin elevates the
      hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally
      enhance subjective craving when confronted with reward cues.

PMID- 22974272
TI  - The right to practice medicine without repercussions: ethical issues in times of
      political strife.
AB  - This commentary examines the incursion on the neutrality of medical personnel now
      taking place as part of the human rights crises in Bahrain and Syria, and the
      ethical dilemmas which these incursions place not only in front of physicians
      practicing in those nations, but in front of the international community as a
      whole.In Bahrain, physicians have recently received harsh prison terms,
      apparently for treating demonstrators who clashed with government forces. In
      Syria, physicians are under the same political pressure to avoid treating
      political demonstrators or to act as informants against their own patients,
      turning them in to government authorities. This pressure has been severe, to the
      point that some physicians have become complicit in the abuse of patients who
      were also political demonstrators.This paper posits that physicians in certain
      countries in the Middle East during the "Arab Spring," specifically Syria and
      Bahrain, are being used as both political pawns and political weapons in clear
      violation of Geneva Convention and World Medical Association guidelines, and that
      this puts them into the most extreme sort of "dual loyalty" dilemma. They are
      being forced to choose between their own safety and well-being and that of their
      patients - a negative sum scenario wherein there is no optimal choice. As such,
      an international call for a United Nations inquiry must be made in order to
      protect the neutrality of medical care and personnel during times of armed
      conflict.

PMID- 22974274
TI  - Emotional stimuli exert parallel effects on attention and memory.
AB  - Because emotional and neutral stimuli typically differ on non-emotional
      dimensions, it has been difficult to determine conclusively which factors
      underlie the ability of emotional stimuli to enhance immediate long-term memory.
      Here we induced arousal by varying participants' goals, a method that removes
      many potential confounds between emotional and non-emotional items. Hungry and
      sated participants encoded food and clothing images under divided attention
      conditions. Sated participants attended to and recalled food and clothing images
      equivalently. Hungry participants performed worse on the concurrent tone
      discrimination task when they viewed food relative to clothing images, suggesting
      enhanced attention to food images, and they recalled more food than clothing
      images. A follow-up regression analysis of the factors predicting memory for
      individual pictures revealed that food images had parallel effects on attention
      and memory in hungry participants, so that enhanced attention to food images did
      not predict their enhanced memory. We suggest that immediate long-term memory for
      food is enhanced in the hungry state because hunger leads to more distinctive
      processing of food images rendering them more accessible during retrieval.

PMID- 22974273
TI  - Construct validity of 2 measures to assess reasons for antipsychotic
      discontinuation and continuation from patients' and clinicians' perspectives in a
      clinical trial.
AB  - BACKGROUND: Little is known about the specific reasons for antipsychotic
      discontinuation or continuation from patients' or clinicians' perspectives. This
      study aimed to assess the construct validity of 2 new measures of the Reasons for
      Antipsychotic Discontinuation/Continuation (RAD): RAD-I (a structured interview
      assessing the patient's perspective) and RAD-Q (a questionnaire assessing the
      clinician's perspective). METHODS: Data were used from a 12-week antipsychotic
      trial of schizophrenia patients in which the RAD was administered at study entry
      and at study completion (or discontinuation). Construct validity was assessed
      through comparisons of RAD responses, clinicians' responses to a standard patient
      disposition form identifying reasons for patient's study discontinuation, and
      several standard psychiatric measures. Percent agreement quantified the
      correspondence between patient and clinician scores. RESULTS: Patients indicating
      lack of improvement/worsening of positive symptoms as a 'somewhat' to 'primary'
      reason for medication discontinuation had statistically significantly less
      improvement in Positive and Negative Syndrome Scale positive score than patients
      not reporting these as a reason (concurrent validity). Similar results were
      observed for the RAD negative symptom, functional, social support, and adherence
      items, whereas the mood and cognitive items were not significantly associated
      with change scores on standard psychiatric measures. Responses to the RAD were
      also weakly associated with variables that theoretically should not be related to
      them (divergent validity). Level of agreement between the clinician- and patient
      rated RAD scores was high (60%-100%). CONCLUSIONS: Initial validation of the RAD
      suggests that the instruments are valid tools for gathering detailed information
      regarding reasons for antipsychotic discontinuation and continuation from
      patients' and clinicians' perspectives.

PMID- 22974275
TI  - Intercellular communication via gap junctions affected by mechanical load in the
      bovine annulus fibrosus.
AB  - Cells in the intervertebral disc, as in other connective tissues including
      tendon, ligament and bone, form interconnected cellular networks that are linked
      via functional gap junctions. These cellular networks may be necessary to affect
      a coordinated response to mechanical and environmental stimuli. Using confocal
      microscopy with fluorescence recovery after photobleaching methods, we explored
      the in situ strain environment of the outer annulus of an intact bovine disc and
      the effect of high-level flexion on gap junction signalling. The in situ strain
      environment in the extracellular matrix of the outer annulus under high flexion
      load was observed to be non-uniform with the extensive cellular processes
      remaining crimped sometimes at flexion angles greater than 25 degrees . A
      significant transient disruption of intercellular communication via functional
      gap junctions was measured after 10 and 20 min under high flexion load. This
      study illustrates that in healthy annulus fibrosus tissue, high mechanical loads
      can impede the functioning of the gap junctions. Future studies will explore more
      complex loading conditions to determine whether losses in intercellular
      communication can be permanent and whether gap junctions in aged and degenerated
      tissues become more susceptible to load. The current research suggests that
      cellular structures such as gap junctions and intercellular networks, as well as
      other cell-cell and cell-matrix interconnections, need to be considered in
      computational models in order to fully understand how macroscale mechanical
      signals are transmitted across scales to the microscale and ultimately into a
      cellular biosynthetic response in collagenous tissues. 

PMID- 22974276
TI  - Lung and heart allocation in the United States.
AB  - Lung and heart allocation in the United States has evolved over the past 20-30
      years to better serve transplant candidates and improve organ utilization. The
      current lung allocation policy, based on the Lung Allocation Score, attempts to
      take into account risk of death on the waiting list and chance of survival
      posttransplant. This policy is flexible and can be adjusted to improve the
      predictive ability of the score. Similarly, in response to the changing clinical
      phenotype of heart transplant candidates, heart allocation policies have evolved
      to a multitiered algorithm that attempts to prioritize organs to the most infirm,
      a designation that fluctuates with trends in therapy. The Organ Procurement and
      Transplantation Network and its committees have been responsive, as demonstrated
      by recent modifications to pediatric heart allocation and mechanical circulatory
      support policies and by ongoing efforts to ensure that heart allocation policies
      are equitable and current. Here we examine the development of US lung and heart
      allocation policy, evaluate the application of the current policy on clinical
      practice and explore future directions for lung and heart allocation.

PMID- 22974277
TI  - Bullous pyoderma gangrenosum: a case report and review of the published work.
AB  - Pyoderma gangrenosum (PG) is an ulcerative skin disorder characterized by
      neutrophilic infiltrations. PG is generally classified into four types: (i)
      ulcerative; (ii) pustular; (iii) bullous; and (iv) vegetative. Among them,
      bullous PG is known as a rare type. Herein, we report a case of bullous PG
      together with a summary of the 12 PG cases treated in our department over the
      previous 15 years, and we review 38 well-documented bullous PG cases (65.8%
      female; aged 18-80 years [mean +/- standard deviation, 51.6 +/- 16.8]) in the
      published work, including the present case, from 1972-2011. Although the disease
      most frequently associated with PG is inflammatory bowel disease, bullous PG is
      most commonly associated with hematological disorders (25/38, 65.8%), which
      indicates the characteristic pathophysiology specific to bullous PG.

PMID- 22974278
TI  - From block clearance to sprint running: characteristics underlying an effective
      transition.
AB  - The aim of this study was to characterize the specifics of the sprint technique
      during the transition from start block into sprint running in well-trained
      sprinters. Twenty-one sprinters (11 men and 10 women), equipped with 74 spherical
      reflective markers, executed an explosive start action. An opto-electronic motion
      analysis system consisting of 12 MX3 cameras (250 Hz; 325,000 pixels) and two
      Kistler force plates (1000 Hz) was used to collect the three-dimensional (3D)
      marker trajectories and ground reaction forces (Nexus, Vicon). The 3D kinematics,
      joint kinetics, and power were calculated (Opensim) and were time normalized to
      100% from the first action after gunshot until the end of second stance after
      block clearance (Matlab). The results showed that during the first stance, power
      generation at the knee plays a significant role in obtaining an effective
      transition, representing 31% of power generation in the lower limb, in the
      absence of preceding power absorption. Furthermore, the sprinter actively
      searches a more forward leaning position to maximize horizontal velocity. Since
      success during sprinting from the second stance onwards involves high hip and
      ankle activation, the above-mentioned three characteristics are specific skills
      required to successfully conclude the transition from start block into sprint
      running.

PMID- 22974280
TI  - Linagliptin monotherapy in type 2 diabetes patients for whom metformin is
      inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III
      trial with a 34-week active-controlled extension.
AB  - AIMS: To investigate the efficacy and safety of linagliptin, a dipeptidyl
      peptidase-4 inhibitor, in type 2 diabetes mellitus (T2DM) patients for whom
      metformin was inappropriate. METHODS: This 1-year double-blind study
      (ClinicalTrials.gov, NCT00740051) enrolled T2DM patients with inadequate
      glycaemic control, treatment-naive [glycated haemoglobin (HbA1c) 7.0-10.0%] or
      previously treated with one oral antidiabetes drug (HbA1c 6.5-9.0% before
      washout), ineligible for metformin because of contraindications (e.g. renal
      impairment) or previous intolerable side effects. Patients were randomized to
      monotherapy with linagliptin 5 mg once daily (n = 151) or placebo (n = 76) for 18
      weeks, after which placebo patients switched to glimepiride 1-4 mg once daily and
      treatments continued for another 34 weeks. The primary endpoint was change from
      baseline in HbA1c after 18 weeks (full-analysis set, last observation carried
      forward). RESULTS: At week 18, adjusted mean difference in change from baseline
      HbA1c (8.1%) was -0.60% (95% confidence interval -0.88, -0.32; p < 0.0001) (
      0.39% with linagliptin, +0.21% with placebo). At week 52, mean HbA1c was
      decreased from baseline in both groups [linagliptin: -0.44%; placebo/glimepiride:
      -0.72% (observed cases)]. Adverse events occurred in 40.4 and 48.7% of
      linagliptin and placebo patients, respectively, during the initial 18 weeks.
      During the 34-week extension, patients receiving linagliptin experienced less
      hypoglycaemia (2.2% vs. 7.8%) and no weight gain (mean change from baseline of 
      0.2 and +1.3 kg, respectively) compared with glimepiride patients. CONCLUSIONS:
      In T2DM patients for whom metformin was inappropriate, linagliptin improved
      glycaemic control and was well tolerated, with less hypoglycaemia and relative
      weight loss compared with glimepiride.

PMID- 22974279
TI  - The effects of prenatal alcohol exposure and attention-deficit/hyperactivity
      disorder on psychopathology and behavior.
AB  - BACKGROUND: This study examined prevalence of psychiatric disorders and
      behavioral problems in children with and without prenatal alcohol exposure (AE)
      and attention-deficit/hyperactivity disorder (ADHD). METHODS: Primary caregivers
      of 344 children (8 to 16 years, M = 12.28) completed the Computerized Diagnostic
      Interview Schedule for Children-IV (C-DISC-4.0) and the Child Behavior Checklist
      (CBCL). Subjects comprised 4 groups: AE with ADHD (AE+, n = 85) and without ADHD
      (AE-, n = 52), and nonexposed with ADHD (ADHD, n = 74) and without ADHD (CON, n =
      133). The frequency of specific psychiatric disorders, number of psychiatric
      disorders (comorbidity), and CBCL behavioral scores were examined using chi
      square and analysis of covariance techniques. RESULTS: Clinical groups had
      greater frequency of all psychiatric disorders, except for anxiety, where the AE-
      and CON groups did not differ. There was a combined effect of AE and ADHD on
      conduct disorder. For comorbidity, children with ADHD had increased psychiatric
      disorders regardless of AE, which did not have an independent effect on
      comorbidity. For CBCL scores, there were significant main effects of AE and ADHD
      on all scores and significant AE * ADHD interactions for Withdrawn/Depressed,
      Somatic Complaints, Attention, and all Summary scores. There was a combined
      effect of AE and ADHD on Externalizing, Total Problems, and Attention Problems.
      CONCLUSIONS: Findings indicate that ADHD diagnosis elevates children's risk of
      psychiatric diagnoses, regardless of AE, but suggest an exacerbated relation
      between AE and ADHD on conduct disorder and externalizing behavioral problems in
      children. Findings affirm a poorer behavioral prognosis for alcohol-exposed
      children with ADHD and suggest that more than 1 neurobehavioral profile may exist
      for individuals with AE.

PMID- 22974281
TI  - Crystal structure of a preacylation complex of the beta-lactamase inhibitor
      sulbactam bound to a sulfenamide bond-containing thiol-beta-lactamase.
AB  - The rise of inhibitor-resistant and other beta-lactamase variants is generating
      an interest in developing new beta-lactamase inhibitors to complement currently
      available antibiotics. To gain insight into the chemistry of inhibitor
      recognition, we determined the crystal structure of the inhibitor preacylation
      complex of sulbactam, a clinical beta-lactamase inhibitor, bound in the active
      site of the S70C variant of SHV-1 beta-lactamase, a resistance enzyme that is
      normally present in Klebsiella pneumoniae. The S70C mutation was designed to
      affect the reactivity of that catalytic residue to allow for capture of the
      preacylation complex. Unexpectedly, the 1.45 A resolution inhibitor complex
      structure revealed that residue C70 is involved in a sulfenamide bond with K73.
      Such a covalent bond is not present in the wild-type SHV-1 or in an apo S70C
      structure also determined in this study. This bond likely contributed
      significantly to obtaining the preacylation complex with sulbactam due to further
      decreased reactivity toward substrates. The intact sulbactam is positioned in the
      active site such that its carboxyl moiety interacts with R244, S130, and T235 and
      its carbonyl moiety is situated in the oxyanion hole. To our knowledge, in
      addition to being the first preacylation inhibitor beta-lactamase complex, this
      is also the first observation of a sulfenamide bond between a cysteine and lysine
      in an active site. Not only could our results aid, therefore, structure-based
      inhibitor design efforts in class A beta-lactamases, but the sulfenamide-bond
      forming approach to yield preacylation complexes could also be applied to other
      classes of beta-lactamases and penicillin-binding proteins with the SXXK motif.

PMID- 22974283
TI  - Framework solids based on copper(II) halides (Cl/Br) and methylene-bridged bis(1
      hydroxybenzotriazole): synthesis, crystal structures, magneto-structural
      correlation, and density functional theory (DFT) studies.
AB  - A methylene-bridged 1-hydroxybenzotriazole derived ligand L [L = 1, 3
      bis(benzotriazol-1-yl)-1,3-dioxapropane] has been synthesized and characterized
      by spectroscopic and structural methods. Reaction of L with two different
      copper(II) halides [CuX(2); X = Br, Cl] in an identical condition yields two
      different compounds of similar compositions, {[Cu(MU-Br)(Br)(MU
      L)](2)}(n).2nH(2)O (1) and {[Cu(MU-Cl)(Cl)(MU-L)](2)}(n).2nH(2)O (2), both being
      characterized by various physicochemical techniques. Single crystal X-ray studies
      reveal that they appear as 2D coordination polymers with similar bridging fashion
      of L. Low temperature magnetic susceptibility measurements reveal
      antiferromagnetic and ferromagnetic behaviors for 1 and 2 with magnetic coupling
      constants J = -15.2 and +1.7 cm(-1), which are in a reasonable agreement with
      their calculated values (J = -9.79 and +0.68 cm(-1) respectively, for 1 and 2).
      The role of bridging halides in the structure and magnetic properties of the
      complexes are investigated, and a possible magneto-structural correlation has
      been established. Influence of spin density of bridging halides on the magnitude
      of coupling constants has been discussed with the help of density functional
      theory (DFT) calculations.

PMID- 22974282
TI  - Tg737 signaling is required for hypoxia-enhanced invasion and migration of
      hepatoma cells.
AB  - BACKGROUND: Although hypoxia is known to promote hepatoma cell invasion and
      migration, little is known regarding the molecular mechanisms of this process.
      Our previous research showed that loss of Tg737 is associated with hepatoma cell
      invasion and migration; therefore, we hypothesized that the Tg737 signal might be
      required for hypoxia-enhanced invasion and migration. METHODS: We established in
      vitro normoxic or hypoxic models to investigate the role of Tg737 in the hypoxia
      enhanced invasion and migration of hepatoma cells. The hepatoma cell lines HepG2
      and MHCC97-H were subjected to normoxic or hypoxic conditions, and the cell
      adhesion, invasion, and migration capabilities were tested. The expression of
      Tg737 under normoxia or hypoxia was detected using western blot assays; cell
      viability was determined using flow cytometry. Furthermore, we created HepG2 and
      MHCC97-H cells that over expressed Tg737 prior to incubation under hypoxia and
      investigated their metastatic characteristics. Finally, we analyzed the
      involvement of critical molecular events known to regulate invasion and
      migration. RESULTS: In this study, Tg737 expression was significantly inhibited
      in HepG2 and MHCC97-H cells following exposure to hypoxia. The down regulation of
      Tg737 expression corresponded to significantly decreased adhesion and increased
      invasion and migration. Hypoxia also decreased the expression/secretion of
      polycystin-1, increased the secretion of interleukin-8 (IL-8), and increased the
      levels of active and total transforming growth factor beta 1 (TGF-beta1),
      critical regulators of cell invasion and migration. Moreover, the decrease in
      adhesiveness and the increase in the invasive and migratory capacities of hypoxia
      treated hepatoma cells were attenuated by pcDNA3.1-Tg737 transfection prior to
      hypoxia. Finally, following the up regulation of Tg737, the expression/secretion
      of polycystin-1 increased, and the secretion of IL-8 and the levels of active and
      total TGF-beta1 decreased correspondingly. CONCLUSIONS: These data provide
      evidence that Tg737 contributes to hypoxia-induced invasion and migration,
      partially through the polycystin-1, IL-8, and TGF-beta1 pathway. Taken together,
      this work suggests that Tg737 is involved in the invasion and migration of
      hepatoma cells under hypoxia, with the involvement of the polycystin-1, IL-8, and
      TGF-beta1 signaling pathway. Tg737 is a potential therapeutic target for
      inhibiting the high invasion and migration potential of hepatoma cells in hypoxic
      regions.

PMID- 22974284
TI  - Chronotherapeutic drug delivery from indomethacin compression coated tablets for
      early morning pain associated rheumatoid arthritis.
AB  - As the main intent of delivering maximum concentration of drug available from the
      dosage form, an oral compression coated tablet (CCT) was intended to develop with
      a predetermined lag time of 6 hrs before immediate release of drug to target
      circadian rhythms of rheumatoid arthritis. Solid dispersions are promising
      approach to enhance drug release, which later will be developed as core tablet
      formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid
      dispersions were formulated with different ratio of drug and carrier (sucrose
      fatty acid esters 1811) using solvent evaporation and melt granulation technique,
      optimized solid dispersion was formulated as core tablet with different diluents.
      Optimized core tablet was compression coated with PEO WSR 303 along with a
      channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before
      immediate release of drug was markedly dependent on weight ratios of polymer and
      channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion
      (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8)
      prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs
      with minimum concentration of channeling agent used, which was also supported
      from the permeability study results. Incompatibility and characterization was
      confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but
      delayed Tmax following oral ingestion of optimized formulation (T8) to human
      volunteers indicated clear lag time before immediate release of drug, which is
      suitable for treating rheumatoid arthritis following circadian rhythm.

PMID- 22974285
TI  - Synthesis of disulfide-cross-linked polypeptide nanogel conjugated with a near
      infrared fluorescence probe for direct imaging of reduction-induced drug release.
AB  - Reduction-sensitive polymeric nanocarrier with near-infrared fluorescence probe
      has been prepared. Disulfide-cross-linked polypeptide nanogel with near-infrared
      fluorescence property (NIRF nanogel) was first synthesized, then the anticancer
      drug doxorubicin was encapsulated into polypeptide core of the NIRF nanogel to
      prepare a drug carrier with near-infrared fluorescence (NIRF prodrug). In vitro
      drug release study of the NIRF prodrug revealed an accelerated release behavior
      in the presence of 10 mM glutathione (GSH). Cellular uptake studies of both the
      NIRF nanogel and NIRF prodrug showed that they could enter cell via endocytosis.
      With the aid of NIRF labeling, direct imaging of the drug release from NIRF
      nanogel was accomplished, and drug molecules released subsequently migrated into
      nucleus while the NIRF nanogel still remained in cytoplasm. In vivo distribution
      of the NIRF nanogel and NIRF prodrug on tumor-bearing nude mice shows that both
      of them accumulated at tumor place at 24 h after tail veil injection via enhanced
      permeability and retention (EPR) effect. The NIRF prodrug prepared here has the
      potential application for the theranosis of cancer.

PMID- 22974287
TI  - Synthesis, characterization of (Z)-N-(1-(2-(2-amino-3-(dimethylamino)
      methyl)phenyl)-5-phenyl-1,3,4, oxadiazol-3(2H)-yl)ethanone analogs as potent
      antimicrobial and hydrogen peroxide scavenging agents.
AB  - A series of (Z)-N-(1-(2-(2-amino-3-((dimethylamino) methyl) phenyl)-5-phenyl
      1,3,4,oxadiazol-3(2H)- yl)ethanone derivatives was prepared and studied for its
      antimicrobial and antioxidant activities. Among the synthesized derivatives,
      compounds (7c) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5-phenyl
      1,3,4-oxadiazol-3(2H)- yl)ethylidene)-4-chloroaniline, (7g) (Z)-N-(1-(2-(2-amino
      3-((dimethylamino)methyl)phenyl)-5-phenyl-1,3,4-oxadiazol- 3(2H)-yl)ethylidene)-4
      nitroaniline and (7i) (Z)-N-(1-(2-(2-amino-3-((dimethylamino)methyl)phenyl)-5
      phenyl-1,3,4- oxadiazol-3(2H)-yl)ethylidene)-4-methoxyaniline were found to be
      the most effective antimicrobial compounds. While the compounds 7c and 7g were
      the most potent antioxidant compounds with significant hydrogen peroxide
      scavenging activity. 

PMID- 22974286
TI  - Human umbilical cord mesenchymal stem cells reduce systemic inflammation and
      attenuate LPS-induced acute lung injury in rats.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) possess potent immunomodulatory
      properties and simultaneously lack the ability to illicit immune responses.
      Hence, MSCs have emerged as a promising candidate for cellular therapeutics for
      inflammatory diseases. Within the context of this study, we investigated whether
      human umbilical cord-derived mesenchymal stem cells (UC-MSCs) could ameliorate
      lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in a rat model.
      METHODS: ALI was induced via injection of LPS. Rats were divided into three
      groups: (1) saline group(control), (2) LPS group, and (3) MSC + LPS group. The
      rats were sacrificed at 6, 24, and 48 hours after injection. Serum,
      bronchoalveolar lavage fluid (BALF), and lungs were collected for cytokine
      concentration measurements, assessment of lung injury, and histology. RESULTS: UC
      MSCs increased survival rate and suppressed LPS-induced increase of serum
      concentrations of pro-inflammatory mediators TNF-alpha, IL-1beta, and IL-6
      without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS
      group exhibited significant improvements in lung inflammation, injury, edema,
      lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as
      well as improved myeloperoxidase (MPO) activity in the lung tissue. Furthermore,
      UC-MSCs decreased malondialdehyde (MDA) production and increased Heme Oxygenase-1
      (HO-1) protein production and activity in the lung tissue. CONCLUSION: UC-MSCs
      noticeably increased the survival rate of rats suffering from LPS-induced lung
      injury and significantly reduced systemic and pulmonary inflammation. Promoting
      anti-inflammatory homeostasis and reducing oxidative stress might be the
      therapeutic basis of UC-MSCs.

PMID- 22974288
TI  - Pharmacophore based 3D-QSAR study of biphenyl derivatives as nonsteroidal
      aromatase inhibitors in JEG-3 cell lines.
AB  - Breast cancer is one of the most high-profile malignant diseases in modern
      society. Among postmenopausal women affected by the disease, a substantial
      portion has breast tumors that are estrogen-receptor positive. A common
      therapeutic intervention for this type of cancer is through endocrine therapy.
      Endocrine agents can act by either diminishing the availability or inhibiting the
      binding of estrogens to ER. Aromatase catalyzes the conversion of androgens to
      estrogens in the final step of the biosynthesis of estrogens and is therefore an
      attractive therapeutic target for inhibition. 3DQSAR pharmacophore modeling
      studies were undertaken for biphenyl derivatives as aromatase inhibitors in JEG-3
      cell lines. A four-point pharmacophore with two H-bond acceptors and two aromatic
      rings as pharmacophoric features was developed. The pharmacophore hypothesis
      yielded a statistically significant 3D-QSAR model, with a correlation coefficient
      of R2 = 0.977 for training set molecules. The generated model showed excellent
      predictive power, with a correlation coefficient of Q2 = 0.946 for an external
      test set. The 3D-QSAR plots illustrated insights into the structure activity
      relationship of these compounds which may help in the design and development of
      potent biphenyl derivatives as new aromatase inhibitors.

PMID- 22974289
TI  - Synthesis and Preliminary In-Vitro Cytotoxic Activity of Various Novel 4-(N
      Substituted Benzothiazolyl) Amino-7-Methoxy-6-(3-Morpholinopropoxy) Quinazoline
      Derivatives.
AB  - A variety of 4-(N-substituted benzothiazolyl) amino-7-methoxy-6-(3
      morpholinopropoxy) quinazoline were synthesized by using various N-substituted 2
      amino benzothiazole, and substituted quinazoline. The structures of these
      compounds were confirmed by IR, Mass and 1HNMR spectral analysis. Newly
      synthesized compounds were tested for their In-Vitro Cytotoxic Activity using MTT
      assay. Results of the study indicated novel series of N-substituted (1, 3
      benzothiazole)-7-methoxy-6-(3-morpholinopropoxy) quinazoline-4-yl-amine
      derivatives are potential class of anticancer agents.

PMID- 22974290
TI  - Diagnostic Assay of Trace Mercury in Muscle Cells.
AB  - An electrochemical diagnostic assay of a trace mercury was performed using
      stripping voltammetry, cyclic voltammetry and chronoamperometry. Three graphite
      pencil electrode systems were used as the working, auxiliary and reference
      electrodes. Fluorine immobilization was performed on the working electrode to
      improve the sensitive low detection limit. Clean seawater was used instead of an
      expensive electrolyte such as buffer solution, acid or base solution. The working
      ranges are better sensitive then observed for analogous method. The result was
      applied to the muscle cell of an earthworm that lived in soil contaminated with
      trace mercury.

PMID- 22974291
TI  - Diagnosis of Dopamine in Brain Neuro Cell Using a Nafion-immobilized Carbon
      Electrode.
AB  - Nafion immobilized onto a graphite pencil carbon electrode (NPE) was used to a
      voltammetric assay of dopamine. The optimum analytical conditions of 150 Hz
      frequency, 150 mV amplitude, -2.0 V accumulation potential and 15 mV increment
      potential were obtained. The SW working range was attained to 0.0-80.0 ugL-1 and
      the CV range of 0.0-90 mgL-1. The statistic relative standard deviation of the
      10.0mgL-1 dopamine was 0.041 (n = 20) at the optimum conditions. The analytical
      detection limit (S/N) was attained to 0.49 ugL-1 (2.62*10-9 M). The developed
      method was applied to diagnostic assay at the fish brain core and diluted nerve
      tissue within a pre-concentration time of 60 sec.

PMID- 22974292
TI  - 3D-QSAR studies on a series of 2,4-thiazolidinedione derivatives: a self-
      organizing molecular field analysis approach to design novel PTP 1B inhibitors.
AB  - Diabetes mellitus is a group of metabolic disorders characterised by chronic
      hyperglycemia resulting either from a deficiency of insulin, or decreased ability
      to transduce the insulin signal, or both. Insulin resistance and beta-cell
      dysfunction are two fundamental defects known to precede the onset of type 2
      diabetes. PTP 1B is considered to function as a negative regulator of insulin
      signal transduction by dephosphorylating phosphotyrosine residues. 2,4
      Thiazolidinediones (TZDs) have long been considered as antihyperglycemic agents
      which act by ameliorating insulin resistance and thereby normalizing elevated
      blood glucose level. A three dimensional quantitative structure-activity
      relationship (3D-QSAR) study was performed on a novel class of thiazolidinedione
      derivatives using self-organizing molecular field analysis (SOMFA) to correlate
      their molecular architecture with observed PTP 1B inhibitory activities. The
      master grid maps derived from the best model were used to display the
      contribution of both electrostatic and shape potential that can be mapped back
      onto structural features relating to the trends in inhibitory activities. The
      present SOMFA study indicated the indispensable molecular features which can be
      further explored for structural modifications of these lead molecules in order to
      optimize PTP 1B inhibitory activity. 

PMID- 22974293
TI  - Design, Synthesis of 6-Substituted-pyrido[3,2-d]pyridazine Derivatives with
      Anticonvulsant Activity.
AB  - The aim of the present paper was to find new compounds with stronger
      anticonvulsant activity and lower neurotoxicity, a novel series of 6-substituted
      pyrido[3,2-d]pyridazine derivatives was synthesized using furo[3,4-b]pyridine-5,7
      dione as the starting material. Their anticonvulsant activities were evaluated by
      the maximal electroshock test (MES) and their neurotoxicity  was measured by the
      rotarod test. The results of these tests demonstrated that N-m-chlorophenyl
      [1,2,4]triazolo- [4,3-b]-pyrido[3,2-d]pyridazin-6-amine (3) was the most potent
      anticonvulsant, with ED50 value of 13.6 mg/kg and protective index (PI = TD50 /
      ED50) values of 7.2 in the MES test. Compound N-m-chlorophenyltetriazolo[5,1-b]
      pyrido[3,2-d]pyridazin-6-amine (19), exhibited a little weaker activity than
      compound 3 in controlling the seizure induced by MES test at the dose of 15.9
      mg/kg, but it possessed lower neurotoxicity with PI value of 13.4, which was
      safer than marketed drug carbamazepine.

PMID- 22974294
TI  - Nanosized tamoxifen-porphyrin-glucose [TPG] conjugate: novel selective anti
      breast-cancer agent, synthesis and in vitro evaluations.
AB  - Tumor and especially breast cancer is among the most common causes of death
      worldwide. Finding novel nanosized therapeutic compounds have important role to
      decrease the chance of death and increase the survival. Cancer cells are highly
      attractive to glucose [with a nanosize bimolecular structure 1nm] as an energy
      source more than normal cell and nanosized therapeutics due to possessing
      different pharmacokinetic and pharmacodynamic have advantageous over classical
      dosage forms in cancer therapy. The aim of the study was to synthesize Glucosamin
      Porphyrin-Tamoxifen [TPG] nanosized complex as a novel selective biocompatible
      anti breast cancer agent. After the synthesis procedure, this complex was
      purified and then tested In Vitro on breast cancer cells [MCF-7] in the absence
      or presence of the red light and found totally successful. The results showed a
      good anti breast cancer activity mediated by the activation of TNF-alpha and
      necrosis/apoptosis pathways for the nanosized complex with no alteration effects
      on blood PT/APTT and glucose or hexokinase levels/ activity. TPG nanoconjugate
      seems to be very good opponents to current anti breast cancer drugs and needs to
      be further investigated in near future.

PMID- 22974295
TI  - The role of healthcare support workers in providing palliative and end-of-life
      care in the community: a systematic literature review.
AB  - Despite the widespread use of Health Care Support Workers (HCSWs) in providing
      palliative and end-of-life care, there is little information available about
      their contributions towards supporting patients who want to be cared for at home
      or to die at home. Between January and April 2011, a systematic review was
      conducted to address two questions: (i) What particular tasks/roles do HCSWs
      perform when caring for people at the end of life and their families to comply
      with their desire to remain at home?; (ii) What are the challenges and supporting
      factors that influence HCSWs' ability to provide palliative and end-of-life care
      in the community? Databases searched for relevant articles published between 1990
      until April 2011 included CINAHL, EMBASE, PsychINFO, British Nursing Index, Web
      of Science, Medline and ASSIA. In total, 1695 papers were identified and their
      titles and abstracts were read. Ten papers met the eligibility criteria of the
      study. After the methodological quality of the studies was appraised, nine papers
      were included in the review. Judgements regarding eligibility and quality were
      undertaken independently by the authors. The findings indicate that HCSWs invest
      a great deal of their time on emotional and social support as well as on
      assisting in the provision of personal care. They are also involved in providing
      care for the dying, respite care for family members and offer domestic support.
      Although it is important to acknowledge the many positive aspects that HCSWs
      provide, the findings suggest three challenges in the HCSWs role: emotional
      attachment, role ambiguity and inadequate training. Support factors such as
      informal peer grief-support groups, sense of cohesiveness among HCSWs and task
      orientation enabled HCSWs to overcome these challenges. To conclude, induction
      and training programmes, a defined period of preceptorship, appropriate support,
      supervision and clearly defined role boundaries may be helpful in reducing the
      challenges identified in HCSWs' roles.

PMID- 22974296
TI  - The association between pressure pain sensitivity, and answers to questionnaires
      estimating psychological stress level in the workplace. A feasibility study.
AB  - OBJECTIVES: To examine the association between pressure pain sensitivity (PPS) at
      the sternum as a measure of persistent stress assessed by questionnaires in a
      working population. METHODS: In 308 office employees PPS measurement was compared
      to Quality of life questionnaires: SF-36 for general physical and mental health,
      the Major Depression Inventory (MDI); 50 specific clinical symptoms for
      persistent stress; subjective evaluation of present and long-term stress level on
      a 7-point ordinal scale. Repeated measures were used to validate the PPS method.
      RESULTS: A significant correlation between PPS and a persistent stress condition
      evaluated from SF-36, MDI and a number of clinical symptoms were found (all p <
      0.01). Persons with PPS >= 60 units had an elevated health risk profile based on
      the questionnaires, when compared to persons with PPS <= 40 (all p < 0.05) (all
      odds ratios > 2). When categorizing a person with PPS >= 60 as persistently
      stressed (27% of subject), and using SF-36, MDI and the number of stress signs
      for risk calculation, the remaining 73% of the subjects, with no elevated health
      risk factors, were identified with an 80% specificity. During home measurements,
      with a full day between measurements, between-measurement correlation coefficient
      was 0.87 and categorization reproducibility 87% (both p < 0.001). CONCLUSIONS: In
      office workers, the PPS measurement correlated to several QOL questionnaires and
      was found useful for persistent stress screening. Validation studies demonstrated
      sufficient reproducibility including during self measurement at home.

PMID- 22974297
TI  - The volume-expanding effects of autologous liquid stored plasma following
      hemorrhage.
AB  - BACKGROUND: Plasma use has increased since studies have suggested that early
      treatment with blood components in trauma with severe hemorrhage may improve
      outcome. Plasma is also commonly used to correct coagulation disturbances in non
      bleeding patients. Little is known about the effects of plasma transfusion on
      plasma volume. We report a prospective interventional study in which the plasma
      volume-expanding effect of autologous plasma was investigated after a controlled
      hemorrhage. METHODS: Plasma obtained by plasmapheresis from nine healthy regular
      blood donors was stored at 2-6 degrees C. Five weeks after donation the subjects
      were bled of 600 ml and then transfused with 600 ml of autologous plasma. Plasma
      volume was estimated using (125)I-albumin before and after bleeding, and
      immediately after plasma transfusion. Plasma volume changes were then estimated
      by measuring changes in hematocrit during the following 3-h period. RESULTS:
      Estimated plasma volume after bleeding was 3170 +/- 320 ml and 3690 +/- 380 ml
      (mean +/- standard deviation) immediately following the transfusion of plasma (p
      0.05). This increase in plasma volume corresponds to 86 +/- 13% of the infused
      volume. Three hours after transfusion, plasma volume was still 3680 +/- 410 ml.
      CONCLUSIONS: Stored liquid plasma has a plasma volume expanding effect up to 86%
      of its infused volume with a duration of at least 3 h.

PMID- 22974298
TI  - Language barrier and its relationship to diabetes and diabetic retinopathy.
AB  - BACKGROUND: Language barrier is an important determinant of health care access
      and health. We examined the associations of English proficiency with type-2
      diabetes (T2DM) and diabetic retinopathy (DR) in Asian Indians living in
      Singapore, an urban city where English is the predominant language of
      communication. METHODS: This was a population-based, cross-sectional study. T2DM
      was defined as HbA1c >=6.5%, use of diabetic medication or a physician diagnosis
      of diabetes. Retinal photographs were graded for the severity of DR including
      vision-threatening DR (VTDR). Presenting visual impairment (VI) was defined as
      LogMAR visual acuity > 0.30 in the better-seeing eye. English proficiency at the
      time of interview was assessed. RESULTS: The analyses included 2,289 (72.1%)
      English-speaking and 885 (27.9%) Tamil-speaking Indians. Tamil-speaking Indians
      had significantly higher prevalence of T2DM (46.2 vs. 34.7%, p < 0.001) and,
      among those with diabetes, higher prevalence of DR (36.0 vs. 30.6%, p < 0.001),
      VTDR (11.0 vs. 6.5%, p < 0.001), and VI (32.4 vs. 14.6%) than English speaking
      Indians. Oaxaca decomposition analyses showed that the language-related
      discrepancies (defined as the difference in prevalence between persons speaking
      different languages) in T2DM, DR, and VTDR could not be fully explained by
      socioeconomic measures. CONCLUSIONS: In an English dominant society, Tamil
      speaking Indians are more likely to have T2DM and diabetic retinopathy. Social
      policies and health interventions that address language-related health
      disparities may help reduce the public health impact of T2DM in societies with
      heterogeneous populations.

PMID- 22974299
TI  - Uncovering the molecular and cellular mechanisms of heart development using the
      zebrafish.
AB  - Over the past 20 years, the zebrafish has emerged as a powerful model organism
      for studying cardiac development. Its ability to survive without an active
      circulation and amenability to forward genetics has led to the identification of
      numerous mutants whose study has helped elucidate new mechanisms in cardiac
      development. Furthermore, its transparent, externally developing embryos have
      allowed detailed cellular analyses of heart development. In this review, we
      discuss the molecular and cellular processes involved in zebrafish heart
      development from progenitor specification to development of the valve and the
      conduction system. We focus on imaging studies that have uncovered the cellular
      bases of heart development and on zebrafish mutants with cardiac abnormalities
      whose study has revealed novel molecular pathways in cardiac cell specification
      and tissue morphogenesis.

PMID- 22974300
TI  - RNA as a structural and regulatory component of the centromere.
AB  - Despite many challenges, great progress has been made in identifying kinetochore
      proteins and understanding their overall functions relative to spindles and
      centromeric DNA. In contrast, less is known about the specialized centromeric
      chromatin environment and how it may be involved in regulating the assembly of
      kinetochore proteins. Multiple independent lines of evidence have implicated
      transcription and the resulting RNA as an important part of this process. Here,
      we summarize recent literature demonstrating the roles of centromeric RNA in
      regulating kinetochore assembly and maintenance. We also review literature
      suggesting that the process of centromeric transcription may be as important as
      the resulting RNA and that such transcription may be involved in recruiting the
      centromeric histone variant CENH3.

PMID- 22974301
TI  - Neural regeneration in Caenorhabditis elegans.
AB  - Axon regeneration is a medically relevant process that can repair damaged
      neurons. This review describes current progress in understanding axon
      regeneration in the model organism Caenorhabditis elegans. Factors that regulate
      axon regeneration in C. elegans have broadly similar roles in vertebrate neurons.
      This means that using C. elegans as a tool to leverage discovery is a legitimate
      strategy for identifying conserved mechanisms of axon regeneration.

PMID- 22974302
TI  - Dosage compensation of the sex chromosomes.
AB  - Differentiated sex chromosomes evolved because of suppressed recombination once
      sex became genetically controlled. In XX/XY and ZZ/ZW systems, the heterogametic
      sex became partially aneuploid after degeneration of the Y or W. Often,
      aneuploidy causes abnormal levels of gene expression throughout the entire
      genome. Dosage compensation mechanisms evolved to restore balanced expression of
      the genome. These mechanisms include upregulation of the heterogametic chromosome
      as well as repression in the homogametic sex. Remarkably, strategies for dosage
      compensation differ between species. In organisms where more is known about
      molecular mechanisms of dosage compensation, specific protein complexes
      containing noncoding RNAs are targeted to the X chromosome. In addition, the
      dosage-regulated chromosome often occupies a specific nuclear compartment. Some
      genes escape dosage compensation, potentially resulting in sex-specific
      differences in gene expression. This review focuses on dosage compensation in
      mammals, with comparisons to fruit flies, nematodes, and birds.

PMID- 22974304
TI  - 5-Methylcytosine DNA demethylation: more than losing a methyl group.
AB  - Demethylation of 5-methylcytosine in DNA is integral to the maintenance of an
      intact epigenome. The balance between the presence or absence of 5-methylcytosine
      determines many physiological aspects of cell metabolism, with a turnover that
      can be measured in minutes to years. Biochemically, addition of the methyl group
      is shared among all living kingdoms and has been well characterized, whereas the
      removal or reversion of this mark seems diverse and much less understood. Here,
      we present a summary of how DNA demethylation can be initiated directly,
      utilizing the ten-eleven translocation (TET) family of proteins, activation
      induced deaminase (AID), or other DNA modifying enzymes, or indirectly, via
      transcription, RNA metabolism, or DNA repair; how intermediates in those pathways
      are substrates of the DNA repair machinery; and how demethylation pathways are
      linked and possibly balanced, avoiding mutations.

PMID- 22974306
TI  - Butterfly-shaped tetrasubstituted carbazole derivatives as a new class of hosts
      for highly efficient solution-processable green phosphorescent organic light
      emitting diodes.
AB  - A new bromination method, where butterfly-shaped tetrasubstituted carbazole
      derivatives TSPFCz and TTPhCz have been designed and synthesized, which possess
      the twist butterfly skeletons and exhibit excellent thermal and morphological
      stabilities, has been adopted. By utilizing these novel compounds as host
      materials, high efficiency solution-processed green phosphorescent organic light
      emitting diodes (PhOLEDs) have been achieved.

PMID- 22974303
TI  - Genetics of Borrelia burgdorferi.
AB  - The spirochetes in the Borrelia burgdorferi sensu lato genospecies group cycle in
      nature between tick vectors and vertebrate hosts. The current assemblage of B.
      burgdorferi sensu lato, of which three species cause Lyme disease in humans,
      originated from a rapid species radiation that occurred near the origin of the
      clade. All of these species share a unique genome structure that is highly
      segmented and predominantly composed of linear replicons. One of the circular
      plasmids is a prophage that exists as several isoforms in each cell and can be
      transduced to other cells, likely contributing to an otherwise relatively anemic
      level of horizontal gene transfer, which nevertheless appears to be adequate to
      permit strong natural selection and adaptation in populations of B. burgdorferi.
      Although the molecular genetic toolbox is meager, several antibiotic-resistant
      mutants have been isolated, and the resistance alleles, as well as some exogenous
      genes, have been fashioned into markers to dissect gene function. Genetic studies
      have probed the role of the outer membrane lipoprotein OspC, which is maintained
      in nature by multiple niche polymorphisms and negative frequency-dependent
      selection. One of the most intriguing genetic systems in B. burgdorferi is vls
      recombination, which generates antigenic variation during infection of mammalian
      hosts.

PMID- 22974307
TI  - Measurements of thermodynamic and optical properties of selected aqueous organic
      and organic-inorganic mixtures of atmospheric relevance.
AB  - Atmospheric aerosol particles can exhibit liquid solution concentrations
      supersaturated with respect to the dissolved organic and inorganic species and
      supercooled with respect to ice. In this study, thermodynamic and optical
      properties of sub- and supersaturated aqueous solutions of atmospheric interest
      are presented. The density, refractive index, water activity, ice melting
      temperatures, and homogeneous ice freezing temperatures of binary aqueous
      solutions containing L(+)-tartaric acid, tannic acid, and levoglucosan and
      ternary aqueous solutions containing levoglucosan and one of the salts
      NH(4)HSO(4), (NH(4))(2)SO(4), and NH(4)NO(3) have been measured in the
      supersaturated concentration range for the first time. In addition, the density
      and refractive index of binary aqueous citric acid and raffinose solutions and
      the glass transition temperatures of binary aqueous L(+)-tartaric acid and
      levoglucosan solutions have been measured. The data presented here are derived
      from experiments on single levitated microdroplets and bulk solutions and should
      find application in thermodynamic and atmospheric aerosol models as well as in
      food science applications.

PMID- 22974308
TI  - Measurement of choroidal perfusion and thickness following systemic sildenafil
      (Viagra((r)) ).
AB  - PURPOSE: To demonstrate anatomic and physiologic changes in the human choroid
      following systemic sildenafil citrate (Viagra(r)) using enhanced depth imaging
      spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high
      frequency digital ultrasound. METHODS: Seven healthy male subjects (mean age 32.7
      years) were evaluated at baseline and 2 hr after ingesting 50 mg of sildenafil.
      Swept-scan high-frequency digital ultrasound and EDI-OCT were utilized to measure
      choroidal perfusion and thickness, respectively. Results were read by masked
      observers. The Wilcoxon signed-rank test and t-test were used to analyse
      differences in choroidal flow and thickness at baseline and 2 hr after ingestion
      of sildenafil. RESULTS: Two hours following sildenafil, increased choroidal
      perfusion was observed in 11 of 12 eyes measured by swept-scan high-frequency
      digital ultrasound. The mean increase was 3.46 (+/-2.00) times baseline with a
      range of 0.47-7.80 times baseline (p = 0.004). Increased choroidal thickness was
      observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness
      increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea and 10.7%
      underneath the fovea (p < 0.001 for all values). CONCLUSIONS: Choroidal perfusion
      and thickness both increase in response to systemic sildenafil. These changes
      could secondarily affect retinal function, explain previously reported clinical
      symptoms and potentially be a useful adjunct for treatment of ocular diseases
      that would benefit from increased choroidal blood flow.

PMID- 22974305
TI  - Probing mechanisms that underlie human neurodegenerative diseases in Drosophila.
AB  - The fruit fly, Drosophila melanogaster, is an excellent organism for the study of
      the genetic and molecular basis of metazoan development. Drosophila provides
      numerous tools and reagents to unravel the molecular and cellular functions of
      genes that cause human disease, and the past decade has witnessed a significant
      expansion of the study of neurodegenerative disease mechanisms in flies. Here we
      review the interplay between oxidative stress and neuronal toxicity. We cover
      some of the studies that show how proteasome degradation of protein aggregates,
      autophagy, mitophagy, and lysosomal function affect the quality control
      mechanisms required for neuronal survival. We discuss how forward genetic screens
      in flies have led to the isolation of a few loci that cause neurodegeneration,
      paving the way for large-scale systematic screens to identify such loci in flies
      as well as promoting gene discovery in humans.

PMID- 22974309
TI  - LBD18 acts as a transcriptional activator that directly binds to the EXPANSIN14
      promoter in promoting lateral root emergence of Arabidopsis.
AB  - Lateral root formation, a developmental process under the control of the plant
      hormone auxin, is a major determinant of root architecture, and defines the
      ability of a plant to acquire nutrients and water. The LATERAL ORGAN BOUNDARIES
      DOMAIN/ASYMMETRIC LEAVES2-LIKE (LBD/ASL) proteins play an important role in the
      lateral organ development of plants, including lateral root formation. However,
      their downstream components and signalling mechanisms are largely unknown. Here,
      we show that auxin-responsive LBD18/ASL20 acts as a specific DNA-binding
      transcriptional activator that directly regulates EXPANSIN14 (EXP14), a gene
      encoding a cell wall-loosening factor that promotes lateral root emergence in
      Arabidopsis thaliana. We showed that LBD18 possesses transcription-activating
      function in both yeast and Arabidopsis protoplasts. We isolated putative LBD18
      target genes by microarray analysis, and identified EXP14 as a direct target of
      LBD18. Dexamethasone-induced expression of LBD18 under the CaMV 35S promoter in
      transgenic Arabidopsis resulted in enhanced expression of GUS fused to the EXP14
      promoter in primordium and overlaying tissues. In contrast, GUS expression under
      the EXP14 promoter in the lbd18 mutant background was significantly reduced in
      the same tissues. Experiments using a variety of molecular techniques
      demonstrated that LBD18 activates EXP14 by directly binding to a specific
      promoter element in vitro and in vivo. Overexpression of EXP14 in Arabidopsis
      resulted in the stimulation of emerged lateral roots, but not primordia, whereas
      EXP14 loss-of-function plants had reduced auxin-stimulated lateral root
      formation. This study revealed the molecular function of LBD18 as a specific DNA
      binding transcription factor that activates EXP14 expression by directly binding
      to its promoter.

PMID- 22974311
TI  - Let's not presuppose that patients take their medications.

PMID- 22974310
TI  - Reduced expression of alpha-synuclein in alcoholic brain: influence of SNCA-Rep1
      genotype.
AB  - alpha-Synuclein has recently been implicated in the pathophysiology of alcohol
      abuse due to its role in dopaminergic neurotransmission. In these studies,
      genetic variability in the alpha-synuclein gene influences its expression which
      may contribute to susceptibility to chronic alcohol abuse. Real-time PCR was used
      to quantify alpha-synuclein mRNA expression in autopsy samples of human
      dorsolateral prefrontal cortex. Because of the association between length of the
      alpha-synuclein-repeat 1 microsatellite marker and expression levels of the gene,
      this marker was genotyped in a Caucasian sample of 126 controls and 117
      alcoholics using capillary gel electrophoresis. The allele and genotype
      frequencies of alpha-synuclein-repeat 1 marker differed significantly between
      alcoholics and controls. Alcoholics had greater frequencies of the shortest
      allele found (267 bp). The shortest allele of the alpha-synuclein-repeat 1 marker
      was associated with decreased expression of alpha-synuclein in prefrontal cortex.
      Individuals with at least one copy of the 267 bp allele were more likely to
      exhibit an alcohol abuse phenotype. These results suggest that individuals with
      the 267 bp allele may be at increased risk of developing alcoholism and that
      genetic variation at the alpha-synuclein-repeat 1 locus may influence alpha
      synuclein expression in the prefrontal cortex. 

PMID- 22974312
TI  - Can you commit to the White House's Joining Forces initiative?

PMID- 22974313
TI  - Current resources for evidence-based practice September/October 2012.

PMID- 22974314
TI  - Aged Residential Care Health Utilisation Study (ARCHUS): a randomised controlled
      trial to reduce acute hospitalisations from residential aged care.
AB  - BACKGROUND: For residents of long term care, hospitalisations can cause distress
      and disruption, and often result in further medical complications. Multi
      disciplinary team interventions have been shown to improve the health of
      Residential Aged Care (RAC) residents, decreasing the need for acute
      hospitalisation, yet there are few randomised controlled trials of these complex
      interventions. This paper describes a randomised controlled trial of a structured
      multi-disciplinary team and gerontology nurse specialist (GNS) intervention
      aiming to reduce residents' avoidable hospitalisations. METHODS/DESIGN: This Aged
      Residential Care Healthcare Utilisation Study (ARCHUS) is a cluster- randomised
      controlled trial (n = 1700 residents) of a complex multi-disciplinary team
      intervention in long-term care facilities. Eligible facilities certified for
      residential care were selected from those identified as at moderate or higher
      risk of resident potentially avoidable hospitalisations by statistical modelling.
      The facilities were all located in the Auckland region, New Zealand and were
      stratified by District Health Board (DHB). INTERVENTION: The intervention
      provided a structured GNS intervention including a baseline facility needs
      assessment, quality indicator benchmarking, a staff education programme and care
      coordination. Alongside this, three multi-disciplinary team (MDT) meetings were
      held involving a geriatrician, facility GP, pharmacist, GNS and senior nursing
      staff. OUTCOMES: Hospitalisations are recorded from routinely-collected acute
      admissions during the 9-month intervention period followed by a 5-month follow-up
      period. ICD diagnosis codes are used in a pre-specified definition of potentially
      reducible admissions. DISCUSSION: This randomised-controlled trial will evaluate
      a complex intervention to increase early identification and intervention to
      improve the health of residents of long term care. The results of this trial are
      expected in early 2013. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry: ACTRN 12611000187943.

PMID- 22974315
TI  - Targeting cells causing split tolerance allows fully allogeneic islet survival
      with minimal conditioning in NOD mixed chimeras.
AB  - Donor-specific tolerance induced by mixed chimerism is one approach that may
      eliminate the need for long-term immunosuppressive therapy, while preventing
      chronic rejection of an islet transplant. However, even in the presence of
      chimerism it is possible for certain donor tissues or cells to be rejected
      whereas others from the same donor are accepted (split tolerance). We previously
      developed a nonmyeloablative protocol that generated mixed chimerism across full
      major histocompatability complex plus minor mismatches in NOD (nonobese diabetic)
      mice, however, these chimeras demonstrated split tolerance. In this study, we
      used radiation chimeras and found that the radiosensitive component of NOD has a
      greater role in the split tolerance NOD mice develop. We then show that split
      tolerance is mediated primarily by preexisting NOD lymphocytes and have
      identified T cells, but not NK cells or B cells, as cells that both resist
      chimerism induction and mediate split tolerance. Finally, after recognizing the
      barrier that preexisting T cells impose on the generation of fully tolerant
      chimeras, the chimerism induction protocol was refined to include
      nonmyeloablative recipient NOD T cell depletion which generated long-term mixed
      chimerism across fully allogeneic barriers. Furthermore, these chimeric NOD mice
      are immunocompetent, diabetes free and accept donor islet allografts.

PMID- 22974316
TI  - Folie a deux homicide and the two-factor model of delusions.
AB  - INTRODUCTION: Cases of folie a deux resulting in homicide challenge traditional
      definitions of delusions. Secondaries who abandon their beliefs soon after
      separation from a primary raise doubts about the status of their delusional
      beliefs at the time of the offence. In this paper, we apply the "two-factor"
      model of delusions to a series of cases of folie a deux resulting in homicide.
      METHOD: A retrospective analysis of five cases. RESULTS: The primary affected
      person appeared to be the source of the delusional content in each of the cases.
      Impairment of belief evaluation was evident to some degree in all patients. There
      appeared to be a range of underlying causes of impaired belief evaluation. The
      transitory nature of the reported beliefs in some secondary cases suggested that
      they were due to motivational rather than neuropathological mechanisms. Social
      isolation contributed to the inability to critically appraise beliefs in most
      cases. CONCLUSION: The two-factor model is a useful method to contrast the
      emergence of a shared delusional belief in primary and secondary patients with
      folie a deux. Folie a deux demonstrates the need to consider the exogenous source
      of delusional content in many patients.

PMID- 22974317
TI  - Aging has greater impact on anaerobic versus aerobic power in trained masters
      athletes.
AB  - This study measured the relative rates of change of the three human energy
      systems across a 30-year age range. A cross-section of highly trained masters
      cyclists (n = 156 males and 17 females; 35-64 years) were tested for maximal
      cycling performance. There were 50 (29%) track sprint cyclists and the remaining
      (71%) were predominantly road cycling specialists. A 10 s peak power test
      measured anaerobic power, a 30 s test measured anaerobic capacity, and a
      progressive test to volitional fatigue was used to determine peak aerobic power.
      Participants' exercise patterns were recorded using a physical activity recall
      questionnaire. Linear regression showed significant changes in anaerobic
      performance with aging. Peak anaerobic power (W . kg-1) declined at a rate (mean
      +/- SEE) of 8.1 +/- 4.1% per decade (P < 0.0001) and anaerobic capacity (kJ . kg
      1) declined at 8.0 +/- 3.3% per decade (P < 0.0001). Peak aerobic power [W . kg
      1] did not change significantly with age [-1.8 +/- 1.5% per decade (P = 0.218)].
      This cross-sectional study showed performance of the two anaerobic energy systems
      declined significantly across the age spectrum with no change in aerobic
      capacity.

PMID- 22974318
TI  - Should we feed back research results in the midst of a study?
AB  - BACKGROUND: This report is an introduction to a series of three research papers
      that describe the evolution of the approaches taken by the Translating Research
      in Elder Care (TREC) research team during its first four years to feed back the
      research findings to study participants. TREC is an observational multi-method
      health services research project underway in 36 nursing homes in the prairie
      provinces of Canada. TREC has actively involved decision makers from the sector
      in all stages from initial planning, through data collection to dissemination
      activities. However, it was not planned as a fully integrated knowledge
      translation project. These three papers describe our progress towards fully
      integrated knowledge translation--with respect to timely and requested feedback
      processes. The first paper reports on the process and outcomes of creating and
      evaluating the feedback of research findings to healthcare aides (unregulated
      health professionals). These aides provide over 80% of the direct care in our
      sample and actively requested the feedback as a condition of their continued
      cooperation in the data acquisition process. The second paper describes feedback
      from nursing home administrators on preliminary research findings (a facility
      annual report) and evaluation of the reports' utility. The third paper discusses
      an approach to providing a more in-depth form of feedback (expanded feedback
      report) at one of the TREC nursing homes. FINDINGS: Survey and interview feedback
      from healthcare aides is presented in the first paper. Overall, healthcare aides'
      opinions about presentation of the feedback report and the understand ability,
      usability, and usefulness of the content were positive. The second paper
      describes the use of telephone interviews with facility administrators and
      indicates that the majority of contextual areas (e.g., staff job satisfaction)
      addressed in facility annual report to be useful, meaningful, and understandable.
      More than one-half of the administrators would have liked to have received
      information on additional areas. The third paper explores how a case study that
      examined how involvement with the TREC study influenced management and staff at
      one of the TREC nursing homes. The importance of understanding organizational
      routines and the impact of corporate restructuring were key themes emerging from
      the case study. In addition, the Director of Care suggested changes to the
      structure and format of the feedback report that would have improved its
      usefulness. CONCLUSIONS: We believe that these findings will inform others
      undertaking integrated knowledge translation activities and will encourage others
      to become more engaged in feedback processes.

PMID- 22974319
TI  - siRNA delivery: from lipids to cell-penetrating peptides and their mimics.
AB  - To deliver siRNA for therapeutic use, several hurdles must be addressed.
      Metabolic degradation must be blocked, and the RNAi cellular machinery is located
      in the cytoplasm, while double-stranded siRNA is large, highly charged and
      impermeable to cell membranes. To date, the solutions to the delivery issues have
      mostly involved different forms of lipid particle encapsulation. Cell-penetrating
      peptides and their mimics or analogues offer a different approach and this is an
      emerging field with the first in vivo examples now reported. Recent reports point
      to lipid receptors being involved in the cellular uptake of both types of
      transporter. This review examines the delivery of siRNA with a focus on cell
      penetrating peptides and their small molecule and oligomeric mimics. The current
      status of siRNA delivery methods in clinical trials is examined. It now seems
      that the goal of delivering siRNA therapeutically is achievable but will they
      form part of a sustainable healthcare portfolio for the future.

PMID- 22974320
TI  - Integrating conjugative elements of the SXT/R391 family from fish-isolated
      Vibrios encode restriction-modification systems that confer resistance to
      bacteriophages.
AB  - Integrating conjugative elements (ICEs) of the SXT/R391 family have been
      described in Vibrios, mainly Vibrio cholerae, and other bacteria as carriers of
      variable gene content conferring adaptive advantages upon their hosts, including
      antimicrobial resistance and motility regulation. However, our knowledge on their
      host range and ecological significance is still limited. Here, we report the
      identification and characterization of ICEVspPor3 and ICEValSpa1, two novel ICEs
      of the SXT/R391 family from fish-isolated Vibrio splendidus and Vibrio
      alginolyticus, respectively. We found that ICEVspPor3 carries tetracycline and
      HgCl(2)  resistance determinants and can be transferred by conjugation to
      Escherichia coli and to several species of marine bacteria including some of the
      major bacterial fish pathogens in marine aquaculture, whereas ICEValSpa1 lacks
      resistance genes. Interestingly, both ICEs harbor genes encoding distinct
      restriction-modification (RM) systems. We demonstrate here that these RM systems,
      when expressed in E. coli, confer protection to infection by T1 bacteriophage and
      by environmental water bacteriophages. Our results provide evidences that the
      variable gene content of ICEs of the SXT/R391 family encodes fitness functions
      beyond those related to antimicrobial resistance and motility regulation and
      suggest that the host range of these elements in the marine environment might be
      broader than expected.

PMID- 22974321
TI  - New trick for an old ligand! The sensing of Zn(II) using a lanthanide based
      ternary Yb(III)-cyclen-8-hydroxyquinoline system as a dual emissive probe for
      displacement assay.
AB  - A novel near-infrared (NIR) emissive lanthanide-based zinc sensor was designed,
      based on the self-assembly in aqueous solution between the nonemissive
      coordinatively unsaturated Yb(III) cyclen complex 2.Yb and the sulfonated 8
      hydroxyquinoline (8-HQS) chromophore, which was employed as a sensitizing
      antenna. The resulting ternary complex, 2.Yb.8-HQS, displayed metal-centered
      emission in the NIR range upon excitation of the antenna with high quantum yield
      of Q = 0.23 +/- 0.03% in pH 7.4 buffered aqueous solution; demonstrating
      efficient sensitization from 8-HQS. The addition of zinc led to quenching of the
      NIR emission as a result of the dissociation of the luminescent ternary 2.Yb.8
      HQS complex, where the 8-HQS antenna was displaced from the Yb(III) center in
      favor of the formation of more stable chelates with Zn(II).  These newly formed
      Zn(II) complexes were shown to exhibit strong green fluorescence; allowing for
      the simultaneous sensing of Zn(II) both within the visible and the NIR regions at
      physiological pH in competitive media. Furthermore, 2.Yb.8-HQS was shown to be
      able to detect Zn(II) with good selectivity and in a reversible manner, even in
      the presence of competitive group (I) and (II) metal ions as well as in the
      presence of several biologically important d-metal ions.

PMID- 22974322
TI  - Clinicopathological risk factors of Stage II colon cancer: results of a
      prospective study.
AB  - AIM: Adjuvant 5-fluorouracil based chemotherapy has demonstrated benefit in Stage
      III colon cancer but still remains controversial in Stage II. The aim of this
      study was to analyse the prognostic impact of clinicopathological factors that
      may help guide treatment decisions in Stage II colon cancer. METHOD: Between 1996
      and 2006 data from patients diagnosed with colorectal cancer at Hospital
      Universitari Bellvitge and its referral comprehensive cancer centre Institut
      Catala d'Oncologia/L'Hospitalet were prospectively included in a database. We
      identified 432 patients with Stage II colon cancer operated on at Hospital
      Universitari Bellvitge. The 5-year relapse-free survival (RFS) and colon-cancer
      specific survival (CCSS) were determined. RESULTS: The 5-year RFS and CCSS were
      83% and 88%, respectively. Lymphovascular or perineural invasion was associated
      with RFS [hazard ratio (HR) 1.84; 95% CI 1.01-3.35]. Gender (women, HR 0.48; 95%
      CI 0.23-1) and lymphovascular or perineural invasion (HR 3.51; 95% CI 1.86-6.64)
      together with pT4 (HR 2.79; 95% CI 1.44-5.41) influenced CCSS. In multivariate
      analysis pT4 and lymphovascular or perineural invasion remained significantly
      associated with CCSS. We performed a risk index with these factors with
      prognostic impact. Patients with pT4 tumours and lymphovascular or perineural
      invasion had a 5-year CCSS of 61%vs the 93% (HR 5.87; 95 CI 2.46-13.97) of those
      without any of these factors. CONCLUSION: pT4 and lymphatic, venous or perineural
      invasion are confirmed as significant prognostic factors in Stage II colon cancer
      and should be taken into account in the clinical validation process of new
      molecular prognostic factors.

PMID- 22974324
TI  - Managing soft tissue sarcomas in a developing country: are prognostic factors
      similar to those of developed world?
AB  - BACKGROUND: Managing soft tissue sarcomas (STS) in a developing country with
      limited financial resources and a poor health referral system is a challenge.
      Presenting late, these extremity STS are prone to recurrence despite apparently
      complete resection. This study aimed to explore and compare the impact of clinico
      pathological factors on recurrence and survival in Pakistan with the
      corresponding figures quoted from the developed world. METHODS: An institutional
      review was performed on all patients with primary STS of the extremities operated
      on between 1994 and 2008. The prognostic influence of clinical, pathologic, and
      treatment variables on local recurrence free survival (LRFS), metastasis free
      survival (MFS) and overall survival (OS) were analyzed by univariate and
      multivariate Cox regression analysis and Kaplan Meier survival curves. RESULTS: A
      total of 84 patients with a mean age of 41.8 +/- 21.9 years were included in the
      study. The local recurrence rate was 14.3% after a median of 6 (mean 7.4) months.
      Metastases occurred in 7 patients (8.3%) and 65 patients were alive without
      evidence of disease after a mean follow-up of 52.6 +/- 39.8 months. Tumor size >
      5 cm, grade 3 tumors and margin < 10 mm significantly increased local recurrence
      rates. A margin >= 10 mm and age < 45 years significantly enhanced cumulative
      survival. Significant multivariate risk factors for metastases were margin < 10
      mm and tumor grade G3. CONCLUSIONS: Despite a poor health referral system in our
      country, our results are no different from those reported from the developed
      world. Surgical margins and tumor grade prognostically influenced LRFS, MFS and
      OS.

PMID- 22974323
TI  - Involvement of autophagy in ovarian cancer: a working hypothesis.
AB  - Autophagy is a lysosomal-driven catabolic process that contributes to preserve
      cell and tissue homeostases through the regular elimination of damaged, aged and
      redundant self-constituents. In normal cells, autophagy protects from DNA
      mutation and carcinogenesis by preventive elimination of pro-oxidative
      mitochondria and protein aggregates. Mutations in oncogenes and oncosuppressor
      genes dysregulate autophagy. Up-regulated autophagy may confer chemo- and radio
      resistance to cancer cells, and also a pro-survival advantage in cancer cells
      experiencing oxygen and nutrient shortage. This fact is the rationale for using
      autophagy inhibitors along with anti-neoplastic therapies. Yet, aberrant hyper
      induction of autophagy can lead to cell death, and this phenomenon could also be
      exploited for cancer therapy. The actual level of autophagy in the cancer cell is
      greatly affected by vascularization, inflammation, and stromal cell infiltration.
      In addition, small non-coding microRNAs have recently emerged as important
      epigenetic modulators of autophagy. The present review focuses on the potential
      involvement of macroautophagy, and on its genetic and epigenetic regulation, in
      ovarian cancer pathogenesis and progression.

PMID- 22974325
TI  - Identification of multiple 5-HT4 partial agonist clinical candidates for the
      treatment of Alzheimer's disease.
AB  - The cognitive impairments observed in Alzheimer's disease (AD) are in part a
      consequence of reduced acetylcholine (ACh) levels resulting from a loss of
      cholinergic neurons. Preclinically, serotonin 4 receptor (5-HT(4)) agonists are
      reported to modulate cholinergic function and therefore may provide a new
      mechanistic approach for treating cognitive deficits associated with AD. Herein
      we communicate the design and synthesis of potent, selective, and brain penetrant
      5-HT(4) agonists. The overall goal of the medicinal chemistry strategy was
      identification of structurally diverse clinical candidates with varying intrinsic
      activities. The exposure-response relationships between binding affinity,
      intrinsic activity, receptor occupancy, drug exposure, and pharmacodynamic
      activity in relevant preclinical models of AD were utilized as key selection
      criteria for advancing compounds. On the basis of their excellent balance of
      pharmacokinetic attributes and safety, two lead 5-HT(4) partial agonist
      candidates 2d and 3 were chosen for clinical development.

PMID- 22974326
TI  - Nutrient-dependent structural changes in S. aureus peptidoglycan revealed by
      solid-state NMR spectroscopy.
AB  - The bacterial cell wall is essential to cell survival and is a major target of
      antibiotics. The main component of the bacterial cell wall is peptidoglycan, a
      cage-like macromolecule that preserves cellular integrity and maintains cell
      shape. The insolubility and heterogeneity of peptidoglycan pose a challenge to
      conventional structural analyses. Here we use solid-state NMR combined with
      specific isotopic labeling to probe a key structural feature of the
      Staphylococcus aureus peptidoglycan quantitatively and nondestructively. We
      observed that both the cell-wall morphology and the peptidoglycan structure are
      functions of growth stage in S. aureus synthetic medium (SASM). Specifically, S.
      aureus cells at stationary phase have thicker cell walls with nonuniformly
      thickened septa compared to cells in exponential phase, and remarkably, 12% (+/
      2%) of the stems in their peptidoglycan do not have pentaglycine bridges
      attached. Mechanistically, we determined that these observations are triggered by
      the depletion of glycine in the nutrient medium, which is coincident with the
      start of the stationary phase, and that the production of the structurally
      altered peptidoglycan can be prevented by the addition of excess glycine. We also
      demonstrated that the structural changes primarily arise within newly synthesized
      peptidoglycan rather than through the modification of previously synthesized
      peptidoglycan. Collectively, our observations emphasize the plasticity in
      bacterial cell-wall assembly and the possibility to manipulate peptidoglycan
      structure with external stimuli.

PMID- 22974327
TI  - Antibacterial activity of phenyl isothiocyanate on Escherichia coli and
      Staphylococcus aureus.
AB  - The present study has been aimed to assess the antibacterial effects of the
      glucosinolate hydrolysis product phenyl isothiocyanate (PITC) against Escherichia
      coli and Staphylococcus aureus. Aspects on the antibacterial mode of action of
      PITC have also been characterized, such as the changes on surface physicochemical
      characteristics and membrane damage. The minimum inhibitory concentration of PITC
      was 1000 ug/mL, for both bacteria. The antimicrobial potential of PITC was
      compared with selected antibiotics (ciprofloxacin, erythromycin, streptomycin,
      tetracycline and spectinomycin), that reported a moderate effect. The combination
      of PITC with ciprofloxacin and erythromycin against S. aureus exhibited a good
      antimicrobial efficacy, due to an additive effect (the diameter of inhibition
      zones increased from 30 to 40 mm for ciprofloxacin and almost the double for
      erythromycin). The other combinations reported unsatisfactory results against
      both bacteria. The study of the physiological changes induced by PITC action
      demonstrated the interaction between the electrophilic compound and the bacterial
      cells at several points that causes changes in membrane properties (decreases
      negative surface charge, increases surface hydrophilicity and electron donor
      characteristics). PITC was also found to disturb membrane function, as manifested
      by phenomena such as cellular disruption and loss of membrane integrity,
      triggering cell death.

PMID- 22974328
TI  - Phototherapy for pityriasis lichenoides: our experience.
AB  - Pityriasis lichenoides is a benign disease that includes a continuous spectrum
      with two polar ends: pityriasis lichenoides et varioliformis acuta (PLEVA) and
      pityriasis lichenoides chronica (PLC). Although its benign and self-limited
      character, treatment is required, both for itch relief and for cosmetic issues.
      The present study is a retrospective analysis of 13 patients (11 PLC and 2 PLEVA)
      treated in our institution with psoralen plus ultraviolet A (PUVA) or ultraviolet
      A combined with ultraviolet B (UVA/UVB) during the period 1998-2011. In the PUVA
      group, complete response was achieved in five patients and partial response in
      two. Total cumulative UVA dose was 84.4 J/cm(2). One patient quit therapy without
      therapeutic response. In the UVA/UVB group, complete response was achieved in two
      patients and partial response in an equal number of patients. One patient did not
      reach a significant improvement. Total cumulative doses were: 26.1 J/cm(2) for
      UVA and 3.62 J/cm(2) for UVB. There were no acute side effects in either
      therapeutic group. In the present study, PUVA phototherapy was preferred for
      patients with more widespread or long-evolving disease, while UVA/UVB was
      selected for patients who presented more recent disease or contraindications for
      PUVA therapy. Regardless of the absence of clinical guidelines, both therapeutic
      options proved to be successful, ascertaining phototherapy as an effective and
      safe option for pityriasis lichenoides patients.

PMID- 22974329
TI  - Improving recognition of delirium in clinical practice: a call for action.
AB  - BACKGROUND: The purpose of this correspondence article is to report opinion
      amongst experts in the delirium field as to why, despite on-going training for
      all health professionals, delirium continues to be under recognised. Consensus
      was obtained by means of two conference workshops and an online survey of members
      of the European Delirium Association.Major barriers to recognition at an
      individual level include ignorance about the benefit of treating delirium. At an
      organisational level, reflecting socio-cultural attitudes, barriers include a low
      strategic and financial priority and the fact that delirium is an orphan
      condition falling between specialties.

PMID- 22974330
TI  - Delineation of the cardiac substructures based on PET-CT and contrast-enhanced CT
      in patients with left breast cancer treated with postoperative radiotherapy.
AB  - The aim of this study is to evaluate the volume differences between contrast
      enhanced CT-based left ventricle (LV) and PET-CT-based LV and assess the impact
      of dose on the substructure volume differences in patients with left breast
      cancer treated with adjuvant radiotherapy. From October 2008 to February 2009, 14
      patients with post-operatively confirmed left breast cancer were enrolled in the
      current study. The patients were scanned using contrast-enhanced CT for
      simulation, and (18)F-FDG PET-CT was employed to display the structure of the
      left ventricle of each before radiotherapy (RT). The LV was delineated based on
      both contrast-enhanced CT and PET-CT. And other substructures, such as the left
      anterior descending coronary artery (LAD), were contoured in each patient, with
      the six-field simple intensity modulated radiotherapy (sIMRT) technique created
      for all. The mean volumes of the left ventricle based on contrast-enhanced CT (LV
      CT) and PET-CT (LV-PET) were found to be 107.296 cm(3) and 112.931 cm(3),
      respectively (p = 0.06). The volume of LV receiving >= 50% prescription dose was
      significantly correlated with the volume of the heart receiving the same dosage
      (gamma = 0.869). There was less correlation between the volume of LAD and that of
      the heart under the same condition (gamma = 0.22). As a conclusion, the left
      ventricle can be delineated effectively based on the image of PET-CT, the
      contrast-enhanced CT based LV can serve as an appropriate alternative. Moreover,
      the volume of LV receiving high dose in RT closely correlated with the volume of
      the heart using sIMRT technique, which may pave the way for further exploring
      radiation-induced cardiac injuries in patients with left breast cancer.

PMID- 22974331
TI  - A dosimetric analysis of tomotherapy based intensity modulated radiation therapy
      with and without bone marrow sparing in gynecologic malignancies.
AB  - Whole pelvic radiotherapy with concurrent chemotherapy is the standard of care
      for locally advanced cervical carcinoma. Published literature reports that the
      pelvic bone marrow (BM) dosimetric parameters of V10 > 90% and V20 > 80% are
      associated with higher rates of hematologic toxicities using this approach. Here,
      we investigate the ability of Tomotherapy based intensity modulated radiation
      therapy (IMRT) to reduce dose to pelvic BM while evaluating dose distribution to
      critical structures and planning target volume (PTV) coverage. Ten patients were
      selected for analysis. Normal structures, whole pelvic BM, PTV contours, and IMRT
      objects were standardized. Two whole pelvis Tomotherapy plans were created for
      each patient, one standard plan, and one with the addition of a BM sparing (BMS)
      constraint (V10 <85%, V20 < 80%). Data were calculated from multiple points with
      regard to BM dose, normal structure dose, and PTV coverage. Differences in dose
      distributions between the two sets of plans were analyzed using a paired t-test.
      The addition of a BMS planning constraint resulted in significant decreases in
      pelvic BM dose at the following dosimetric points: V5, V10, V15, V20, V30, V40,
      V50, and mean dose (p < 0.05 for all points). There were no significant
      differences in dose to small bowel, bladder or rectum, with the exception of one
      data point (small bowel V30, p = 0.004) between the two sets of plans. There was
      no sacrifice of PTV coverage or loss of homogeneity with the addition of a BMS
      planning constraint. BMS-IMRT significantly reduces radiation dose to the pelvic
      BM while maintaining the ability to spare dose to the small bowel, bladder and
      rectum. The planning constraints were met without violation of study criteria,
      and without sacrifice of PTV coverage. Further investigation is warranted to
      determine if rates of hematologic toxicity improve with utilization of
      Tomotherapy based BMS-IMRT.

PMID- 22974332
TI  - Dosimetry study of [I-131] and [I-125]- meta-iodobenz guanidine in a simulating
      model for neuroblastoma metastasis.
AB  - The physical properties of I-131 may be suboptimal for the delivery of
      therapeutic radiation to bone marrow metastases, which are common in the natural
      history of neuroblastoma.  In vitro and preliminary clinical studies have implied
      improved efficacy of I-125 relative to I-131 in certain clinical situations,
      although areas of uncertainty remain regarding intratumoral dosimetry. This
      prompted our study using human neuroblastoma multicellular spheroids as a model
      of metastasis. 3D dose calculations were made using voxel-based Medical Internal
      Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose
      distributions for I-131 and I-125 labeled mIBG were calculated for spheroids
      (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative
      dose delivered to the tumors was compared for the same limiting dose to the bone
      marrow. Based on the same data, arguments were advanced based upon the principles
      of tumor control probability (TCP) to emphasize the potential theoretical utility
      of I-125 over I-131 in specific clinical situations. I-125-mIBG can deliver a
      higher and more uniform dose to tumors compared to I-131 mIBG without increasing
      the dose to the bone marrow. Depending on the tumor size and biological half
      life, the relative dose to tumors of less than 1 mm diameter can increase several
      fold. TCP calculations indicate that tumor control increases with increasing
      administered activity, and that I-125 is more effective than I-131 for tumor
      diameters of 0.01 cm or less. This study suggests that I-125-mIBG is
      dosimetrically superior to I-131-mIBG therapy for small bone marrow metastases
      from neuroblastoma. It is logical to consider adding I-125-mIBG to I-131-mIBG in
      multi-modality therapy as these two isotopes could be complementary in terms of
      their cumulative dosimetry.

PMID- 22974333
TI  - Knockdown of Cdc6 inhibits proliferation of tongue squamous cell carcinoma
      Tca8113 cells.
AB  - The present study aimed at evaluating the effects of Cdc6 downregulation on the
      proliferation of Tca8113 cells. Two lentiviral vectors (KD1 and KD2) expression
      cdc6 siRNA were constructed and then infected into Tca8113 cells. Real-time PCR
      and Western blot analysis were performed to detect the mRNA and protein
      expression of Cdc6. MTT assays were employed to delineate the growth curves, and
      flow cytometry was performed to assess cell-cycle progression and apoptosis in
      Tca8113 cells. Following infection with the lentiviral vectors, real-time PCR and
      Western blot analysis revealed that Cdc6 expression was markedly suppressed in
      Tca8113 cells. When compared with the negative control group, the mRNA expression
      of Cdc6 was reduced by 50% and 65% and the protein expression by 65.87% and
      79.38% in cells harboring KD1 or KD2, respectively. Cell growth was slowed, and
      the growth inhibition rate was 25.84% and 30.34% in Tca8113 cells following
      infection with KD1 or KD2, respectively. In addition, cell-cycle progression was
      altered. In KD- infected Tca8113 cells, the proportion of cells in the S phase
      was markedly reduced, but the proportion in the G1 phase was significantly
      increased; this was accompanied by an increase in cell apoptosis. Downregulation
      of Cdc6 effectively inhibited the proliferation of Tca8113 cells.

PMID- 22974334
TI  - Robotic stereotactic radiosurgery in patients with unresectable glomus jugulare
      tumors.
AB  - We evaluated the treatment results of robotic stereotactic radiosurgery (SRS) in
      our patients with unresectable glomus jugulare tumors (GJTs). The medical charts
      of fourteen patients with GJT, who were treated with robotic SRS, were
      retrospectively evaluated. The gross tumor volume was described as the clinical
      target volume. The median dose to the tumor was 25 Gy in median 5 fractions. The
      dose was normalized to 80% isodose line. All patients were evaluated for tumor
      growth and clinical outcome every 6 months in the first 2 years and then
      annually. Median follow-up was 39 months (range, 7-60 months). Lesions were
      stable in 8 patients, and tumor regression was observed in 6 patients. We did not
      observe any treatment related toxicity in our patients. In conclusion, according
      to our early experience, robotic SRS seems to be successful treatment option in
      the management of unresectable GJTs.

PMID- 22974335
TI  - Suppressed expression of autophagosomal protein LC3 in cortical tubers of
      tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is characterized by benign tumors and
      hamartomas, including cortical tubers. Hamartin and tuberin, encoded by the TSC 1
      and 2 genes, respectively, constitute a functional complex that negatively
      regulates the mammalian target of rapamycin (mTOR) signaling pathway, eventually
      promoting the induction of autophagy. In the present study, we assessed the
      induction of autophagy in cortical tubers surgically removed from seven patients
      with TSC in comparison with five controls of cortical tissue taken from non-TSC
      patients with epilepsy. Immunoblotting demonstrated a marked reduction of LC3B-I
      and LC3B-II in tubers relative to the controls. In tubers, strong, diffuse and
      dot-like immunoreactivity (IR) for LC3B was observed in dysmorphic neurons and
      balloon cells, but LC3B-IR in other neurons with normal morphology was
      significantly weaker than that in neurons in the controls. Immunoelectron
      microscopy revealed diffuse distribution of LC3B-IR within the cytoplasm of
      balloon cells. The dot-like pattern may correspond to abnormal aggregation bodies
      involving LC3. In an autopsy patient with TSC, we observed that LC3B-IR in
      neurons located outside of the tubers was preserved. Thus, autophagy is
      suppressed in tubers presumably through the mTOR pathway, and possibly a
      pathological autophagy reaction occurs in the dysmorphic neurons and balloon
      cells.

PMID- 22974337
TI  - A computational model for generation of the P300 evoked potential component.
AB  - The P300 is an endogenously evoked potential with amplitude and latency depending
      on the amount of information carried by the stimulus rather than its physical
      characteristics. It has been suggested that P300 is a manifestation of the
      context updating mechanism in the human working memory. We present a neural
      network-based model that mimics the learning and forgetting mechanisms of
      external stimuli in the human working memory that are believed to be responsible
      for P300 generation. A modified version of the Hebbian learning rule has been
      devised to govern the weight dynamics of the network. The model was validated by
      comparing the characteristics of simulated P300 with actual experimental findings
      such as the relationship between P300 amplitude and stimulus probability, and
      task relevance. The results show that the proposed P300 model mimics many aspects
      of the nervous system responsible for P300 generation.

PMID- 22974338
TI  - Qualitative exploration of public and smoker understanding of, and reactions to,
      an endgame solution to the tobacco epidemic.
AB  - BACKGROUND: There is increasing interest in ending the tobacco epidemic and in
      applying 'endgame' solutions to achieve that goal at national levels. We explored
      the understanding of, and reactions to, a tobacco-free vision and an endgame
      approach to tobacco control among New Zealand smokers and non-smokers. METHODS:
      We recruited participants in four focus groups held in June 2009: Maori
      (indigenous people) smokers (n=7); non-Maori smokers (n=6); Maori non-smokers
      (n=7); and non-Maori non-smokers (n=4). Participants were from the city of
      Whanganui, New Zealand. We introduced to them the vision of a tobacco-free New
      Zealand and the concept of a semi-autonomous agency (Tobacco-Free Commission
      [TFC]) that would control the tobacco market as part of an endgame approach.
      RESULTS: There was mostly strong support for the tobacco-free New Zealand vision
      among all groups of participants. The reason most commonly given for supporting
      the vision was to protect children from tobacco. Most participants stated that
      they understood the TFC concept and reacted positively to it. Nevertheless,
      rather than focusing on organisational or structural arrangements, participants
      tended to focus on supporting the specific measures which a future TFC might
      facilitate such as plain packaging of tobacco products. Various concerns were
      also raised around the TFC, particularly around the feasibility of its
      establishment. CONCLUSIONS: We were able to successfully communicate a complex
      and novel supply-side focused tobacco control policy intervention to smokers and
      non-smokers. The findings add to the evidence from national surveys that there is
      public support, including from smokers, for achieving a tobacco-free vision and
      using regulatory and policy measures to achieve it. Support for such measures may
      be enhanced if they are clearly communicated and explained with a rationale which
      stresses protecting children and future generations from tobacco smoking.

PMID- 22974339
TI  - Effects of duration of stay in temperate area on thermoregulatory responses to
      passive heat exposure in tropical south-east Asian males residing in Japan.
AB  - BACKGROUND: In this study, we investigated the effects of duration of stay in a
      temperate area on the thermoregulatory responses to passive heat exposure of
      residents from tropical areas, particularly to clarify whether they would lose
      their heat tolerance during passive heat exposure through residence in a
      temperate country, Japan. METHODS: We enrolled 12 males (mean +/- SE age 25.7 +/-
      1.3 years) from south-east Asian countries who had resided in Japan for a mean of
      24.5 +/- 5.04 months, and 12 Japanese males (age 24.1 +/- 0.9 years). Passive
      heat exposure was induced through leg immersion in hot water (42 degrees C) for
      60 minutes under conditions of 28 degrees C air temperature and 50% relative
      humidity. RESULTS: Compared with the Japanese group, the tropical group displayed
      a higher pre-exposure rectal temperature (P < 0.01) and a smaller increase in
      rectal temperature during 60 minutes of leg immersion (P = 0.03). Additionally,
      the tropical group showed a tendency towards a lower total sweat rate (P = 0.06)
      and lower local sweat rate on the forehead (P = 0.07). The tropical group also
      had a significantly longer sweating onset time on the upper back (P = 0.04)
      compared with the Japanese groups. The tropical group who stayed in Japan for >
      23 months sweated earlier on the forehead and upper back than those who stayed in
      Japan < 11 months (P < 0.01 and P = 0.03 for the forehead and upper back,
      respectively). There was a positive correlation between duration of stay in Japan
      and total sweat rate (r = 0.58, P <0.05), and negative correlations between
      duration of stay and sweating onset time on the forehead (r = -0.73, P = 0.01)
      and on the upper back (r = -0.66, P = 0.02). Other physiological indices measured
      in this study did not show any difference between the subjects in the tropical
      group who had lived in Japan for a shorter time and those who had lived there for
      a longer time. CONCLUSIONS: We conclude that the nature of heat acclimatization
      of the sweating responses to passive heat exposure that are acquired from long
      term heat acclimatization is decayed by a stay in a temperate area, as shown by
      the subjects in our tropical group. We did not find any evidence of a decay in
      the other physiological indices, indicating that heat tolerance acquired from
      long-term heat acclimatization is not completely diminished through residence in
      a temperate area for less than 4 years, although some aspects of this heat
      tolerance may be decayed.

PMID- 22974340
TI  - Bombacaceae: a phytochemical review.
AB  - CONTEXT: Bombacaceae is a small family of the order Malvales and contains about
      28 genera and 200 species. Members of this family are not only showy ornamentals
      but they possess significant economical and commercial reputation as well. In
      addition, various plant parts of several species are widely used as foods and
      traditional medicines in many parts of the world. OBJECTIVE: Chemical analyses of
      Bombacaceae species have recently yielded a number of important phytocompounds
      belonging to different classes. Hence, this work represents a comprehensive
      appraisal of the phytochemical studies conducted on Bombacaceae plants. MATERIALS
      AND METHODS: Searches were conducted using electronic databases (e.g., Medline,
      Pubmed, Academic Journals, and Springer Link); general web searches were also
      undertaken using Google applying some related search terms "e.g., Bombacaceae,
      phytochemical studies of Bombacaeae plants, and chemical investigation of
      Bombacaeae", journals and scientific theses. The bibliographies of papers
      relating to the review subject were also searched for further relevant
      references. RESULTS: Chemical investigations were concentrated primarily on
      certain species leaving fertile fields for further phytopharmacological research.
      CONCLUSION: The reviewed findings present Bombacaceae species as an untapped
      reservoir of phytocompounds which may play a supportive role in the
      pharmaceutical field and will be of high chemotaxonomic value within this
      recently separated family.

PMID- 22974342
TI  - Comparison of DNA preservation methods for environmental bacterial community
      samples.
AB  - Field collections of environmental samples, for example corals, for molecular
      microbial analyses present distinct challenges. The lack of laboratory facilities
      in remote locations is common, and preservation of microbial community DNA for
      later study is critical. A particular challenge is keeping samples frozen in
      transit. Five nucleic acid preservation methods that do not require cold storage
      were compared for effectiveness over time and ease of use. Mixed microbial
      communities of known composition were created and preserved by DNAgard(TM),
      RNAlater((r)), DMSO-EDTA-salt (DESS), FTA((r)) cards, and FTA Elute((r)) cards.
      Automated ribosomal intergenic spacer analysis and clone libraries were used to
      detect specific changes in the faux communities over weeks and months of storage.
      A previously known bias in FTA((r)) cards that results in lower recovery of pure
      cultures of Gram-positive bacteria was also detected in mixed community samples.
      There appears to be a uniform bias across all five preservation methods against
      microorganisms with high G + C DNA. Overall, the liquid-based preservatives
      (DNAgard(TM), RNAlater((r)), and DESS) outperformed the card-based methods. No
      single liquid method clearly outperformed the others, leaving method choice to be
      based on experimental design, field facilities, shipping constraints, and
      allowable cost.

PMID- 22974341
TI  - Solution structure of the sortase required for efficient production of infectious
      Bacillus anthracis spores.
AB  - Bacillus anthracis forms metabolically dormant endospores that upon germination
      can cause lethal anthrax disease in humans. Efficient sporulation requires the
      activity of the SrtC sortase (BaSrtC), a cysteine transpeptidase that covalently
      attaches the BasH and BasI proteins to the peptidoglycan of the forespore and
      predivisional cell, respectively. To gain insight into the molecular basis of
      protein display, we used nuclear magnetic resonance to determine the structure
      and backbone dynamics of the catalytic domain of BaSrtC (residues Ser(56)
      Lys(198)). The backbone and heavy atom coordinates of structurally ordered amino
      acids have coordinate precision of 0.42 +/- 0.07 and 0.82 +/- 0.05 A,
      respectively. BaSrtC(Delta55) adopts an eight-stranded beta-barrel fold that
      contains two short helices positioned on opposite sides of the protein.
      Surprisingly, the protein dimerizes and contains an extensive, structurally
      disordered surface that is positioned adjacent to the active site. The surface is
      formed by two loops (beta2-beta3 and beta4-H1 loops) that surround the active
      site histidine, suggesting that they may play a key role in associating BaSrtC
      with its lipid II substrate. BaSrtC anchors proteins bearing a noncanonical LPNTA
      sorting signal. Modeling studies suggest that the enzyme recognizes this
      substrate using a rigid binding pocket and reveals the presence of a conserved
      subsite for the signal. This first structure of a class D member of the sortase
      superfamily unveils class-specific features that may facilitate ongoing efforts
      to discover sortase inhibitors for the treatment of bacterial infections.

PMID- 22974343
TI  - Closure of defunctioning loop ileostomy is associated with considerable
      morbidity.
AB  - AIM: An elective defunctioning ileostomy is commonly employed to attenuate the
      morbidity that may arise from distal anastomotic leakage. The magnitude of risk
      associated with subsequent ileostomy closure is difficult to estimate as many of
      the data arise from small series. This study looked at the rate of complications
      and predictive factors in a large series of patients. METHODS: The National
      Surgical Quality Improvement Program database was queried for patients who had an
      elective closure of ileostomy between 2005 and 2010. Patient demographics,
      preoperative risk factors and operative variables were recorded. The primary
      outcome was occurrence of major (mortality, sepsis, return to the operating room,
      renal failure, major cardiac, neurological or respiratory episode) or minor
      (wound infection, urinary tract infection) complications within 30 days.
      Univariate and multivariate regression was used to evaluate the effect of these
      clinical factors on the complication rate. RESULTS: In total, 5401 patients
      underwent closure of ileostomy, of whom 502 (9.3%) patients had major
      complications. The incidence of minor complications was 8.4% (452 patients).
      There were 32 (0.6%) deaths. American Society of Anesthesiologists grade,
      functional status, prolonged operative time, history of chronic obstructive
      pulmonary disease, dialysis and disseminated cancer were independent predictors
      of major complications. There was no significant increase in complication rates
      in patients over the age of 80. Major complications were associated with a
      significant increase in postoperative stay (13.9 vs 4.7 days, P < 0.0001).
      CONCLUSION: Closure of ileostomy is associated with a significant complication
      rate. It may use as many resources as the primary surgery and is not a minor
      follow-up operation.

PMID- 22974344
TI  - Dentist education and labour market in Mexico: elements for policy definition.
AB  - BACKGROUND: Here, the educational and labour market characteristics of Mexican
      dentists are revised. Dentistry is a health profession that has been scarcely
      studied in developing countries. This analysis attempts to understand the
      relationships and gaps between the supply and demand of dentists in the country.
      Around 5000 new dentists graduate every year looking for a place in the labour
      market. METHODS: A cross-sectional study with exploratory, descriptive and
      correlational scope was carried out between 2006 and 2008. Analyses of
      quantitative data on dentists from national surveys and occupational statistics
      were complemented with qualitative information provided by 43 key informants in
      five Mexican states. RESULTS: The 2008 dentist labour market can be characterized
      as follows: 75% worked in the private sector, most of them independently; more
      than two-thirds were women; the proportion of specialists was low (slightly more
      than 10%); unemployment was more than 20% and labour wastage was nearly 40%, with
      most wastage corresponding with female dentists. The increase in the number of
      dentists entering the labour market during the last two decades is more related
      to the educational market than to the population's health needs and the number of
      dentists actually required to meet them. CONCLUSIONS: The problems identified in
      the Mexican dentist labour market necessitate urgent intervention on behalf of
      regulatory bodies in order to balance the tendencies of supply and demand in the
      number of trained professionals as well as in their incorporation into different
      market areas. Adequate policies are required to increase the likelihood of
      achieving this objective.

PMID- 22974345
TI  - The role of targeted viral load testing in diagnosing virological failure in
      children on antiretroviral therapy with immunological failure.
AB  - OBJECTIVES: To determine the improvement in positive predictive value of
      immunological failure criteria for identifying virological failure in HIV
      infected children on antiretroviral therapy (ART) when a single targeted viral
      load measurement is performed in children identified as having immunological
      failure. METHODS: Analysis of data from children (<16 years at ART initiation) at
      South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are
      performed 6-monthly. Immunological failure was defined according to both WHO 2010
      and United States Department of Health and Human Services (DHHS) 2008 criteria.
      Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two
      consecutive occasions <365 days apart in a child on ART for >=18 months. RESULTS:
      Among 2798 children on ART for >=18 months [median (IQR) age 50 (21-84) months at
      ART initiation], the cumulative probability of confirmed virological failure by
      42 months on ART was 6.3%. Using targeted viral load after meeting DHHS
      immunological failure criteria rather than DHHS immunological failure criteria
      alone increased positive predictive value from 28% to 82%. Targeted viral load
      improved the positive predictive value of WHO 2010 criteria for identifying
      confirmed virological failure from 49% to 82%. CONCLUSION: The addition of a
      single viral load measurement in children identified as failing immunologically
      will prevent most switches to second-line treatment in virologically suppressed
      children.

PMID- 22974346
TI  - Fe(II) complexes that mimic the active site structure of acetylacetone
      dioxygenase: O2 and NO reactivity.
AB  - Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the
      dioxygen-dependent degradation of beta-dicarbonyl compounds. The Dke1 active site
      contains a nonheme monoiron(II) center facially ligated by three histidine
      residues (the 3His triad); coordination of the substrate in a bidentate manner
      provides a five-coordinate site for O(2) binding. Recently, we published the
      synthesis and characterization of a series of ferrous beta-diketonato complexes
      that faithfully mimic the enzyme-substrate intermediate of Dke1 (Park, H.; Baus,
      J.S.; Lindeman, S.V.; Fiedler, A.T. Inorg. Chem.2011, 50, 11978-11989). The 3His
      triad was modeled with three different facially coordinating N3 supporting
      ligands, and substituted beta-diketonates (acac(X)) with varying steric and
      electronic properties were employed. Here, we describe the reactivity of our Dke1
      models toward O(2) and its surrogate nitric oxide (NO), and report the synthesis
      of three new Fe(II) complexes featuring the anions of dialkyl malonates. Exposure
      of [Fe((Me2)Tp)(acac(X))] complexes (where (R2)Tp = hydrotris(pyrazol-1-yl)borate
      with R-groups at the 3- and 5-positions of the pyrazole rings) to O(2) at -70 
      degrees C in toluene results in irreversible formation of green chromophores
      (lambda(max) ~750 nm) that decay at temperatures above -60  degrees C.
      Spectroscopic and computational analyses suggest that these intermediates contain
      a diiron(III) unit bridged by a trans MU-1,2-peroxo ligand. The green chromophore
      is not observed with analogous complexes featuring (Ph2)Tp and (Ph)TIP ligands
      (where (Ph)TIP = tris(2-phenylimidazoly-4-yl)phosphine), since the steric bulk of
      the phenyl substituents prevents formation of dinuclear species. While these
      complexes are largely inert toward O(2), (Ph2)Tp-based complexes with dialkyl
      malonate anions exhibit dioxygenase activity and thus serve as functional Dke1
      models. The Fe/acac(X) complexes all react readily with NO to yield high-spin (S
      = 3/2) {FeNO}(7) adducts that were characterized with crystallographic,
      spectroscopic, and computational methods. Collectively, the results presented
      here enhance our understanding of the chemical factors involved in the oxidation
      of aliphatic substrates by nonheme iron dioxygenases.

PMID- 22974347
TI  - Functional corneal endothelium derived from corneal stroma stem cells of neural
      crest origin by retinoic acid and Wnt/beta-catenin signaling.
AB  - Corneal endothelial dysfunction remains a major indication for corneal
      transplantation. Both corneal endothelial cells and stromal cells originate from
      the neural crest, but have distinct phenotypes and function in the adult cornea.
      We previously reported that stem cells isolated from the adult corneal stroma
      [cornea-derived precursors (COPs)] show characteristics of multipotent neural
      crest-derived stem cells. In this study, we report the induction of functional
      tissue-engineered corneal endothelium (TECE) from mouse and human COPs. TECE was
      engineered from Wnt1-Cre/Floxed EGFP mouse COPs in a medium containing retinoic
      acid and glycogen synthase kinase (GSK) 3beta inhibitor (activator of Wnt/beta
      catenin signaling). The expression levels of major markers characterizing corneal
      endothelial function (Atp1a1, Slc4a4, Car2, Col4a2, Col8a2, and Cdh2) were
      significantly upregulated. Both retinoic acid and GSK 3beta inhibitor upregulated
      the expression of Pitx2, a homeobox gene involved in the development of the
      anterior segment of the eye. GSK 3beta inhibitor increased Atp1a1 expression and
      Na,K-ATPase pump activity of TECE, which was significantly higher than COPs or
      control 3T3 cells, and 2.6-fold higher than cultured mouse corneal endothelial
      cells. Mouse TECE transplanted into rabbit corneas maintained transparency and
      corneal thickness, whereas control corneas without TECE showed marked edema and
      increased corneal thickness. Furthermore, we successfully induced TECE from human
      COPs, and human TECE transplanted into rabbit corneas also maintained corneal
      transparency and thickness. This protocol enables efficient production of corneal
      endothelium from corneal stromal stem cells by direct induction, which may lead
      to a novel stem cell therapy for corneal endothelial dysfunction.

PMID- 22974348
TI  - Using stormwater hysteresis to characterize karst spring discharge.
AB  - Discharge from karst springs contains a mixture of conduit and matrix water, but
      the variations in groundwater mixing are poorly known. Storm events present an
      opportunity to try to map flow components because water entering during storms is
      more dilute and provides a tracer as it mixes with pre-event water along the
      flowpath from the recharge area to discharge at a spring. We used hysteresis
      plots of Mg/Ca ratios in a spring in the Cumberland Valley of Pennsylvania to map
      conduit (higher Ca) vs. diffuse (higher Mg) sources of recharge. We observed two
      types of temporal heterogeneity: within a storm event and from storm to storm.
      The timing of the variation in Mg/Ca suggested sources of mixing waters. An
      increase in the Mg/Ca ratio at the beginning of some storms while conductivity
      declined suggested diffuse recharge through the epikarst. The rapid changes in
      Mg/Ca ratios for low-intensity events probably occurred as the rainfall waxed and
      waned and illustrate that a variety of flowpaths are available at this spring
      because additional flushing of Mg occurred. In contrast, the conductivity
      hysteresis began with dilute water initially and rotation was similar from storm
      to storm. Hysteresis plots of the Mg/Ca ratio have the potential of revealing
      more of the complexity in discharge than conductivity alone. A better
      understanding of flow components in karst is needed to protect these aquifers as
      a groundwater resource. 

PMID- 22974349
TI  - An antidote for groupthink--a qualified lottery for research dollars.

PMID- 22974350
TI  - Kicking the digital dog: a longitudinal investigation of young adults'
      victimization and cyber-displaced aggression.
AB  - Using the general strain theory as a theoretical framework, the present
      longitudinal study investigated both face-to-face and cyber victimization in
      relation to cyber-displaced aggression. Longitudinal data were collected from 130
      (70 women) young adults who completed measures assessing their victimization
      (face-to-face and cyber), cyber aggression, and both face-to-face and cyber
      displaced aggression. Findings indicated that victimization in both social
      contexts (face-to-face and cyber) contributed to cyber-displaced aggression 6
      months later (Time 2), after controlling for gender, cyber aggression, face-to
      face displaced aggression, and cyber-displaced aggression at Time 1. A
      significant two-way interaction revealed that Time 1 cyber victimization was more
      strongly related to Time 2 cyber-displaced aggression when young adults had
      higher levels of face-to-face victimization at Time 1. Implications of these
      findings are discussed as well as a call for more research investigating
      displaced aggression in the cyber context.

PMID- 22974351
TI  - Online gaming addiction? Motives predict addictive play behavior in massively
      multiplayer online role-playing games.
AB  - Recently, there have been growing concerns about excessive online gaming. Playing
      Massively Multiplayer Online Role-Playing Games (MMORPGs) appears to be
      particularly problematic, because these games require a high degree of commitment
      and time investment from the players to the detriment of occupational, social,
      and other recreational activities and relations. A number of gaming motives have
      been linked to excessive online gaming in adolescents and young adults. We
      assessed 175 current MMORPG players and 90 nonplayers using a Web-based
      questionnaire regarding their gaming behavior, problems as consequences of
      gaming, and game motivations and tested their statistical associations. Results
      indicated that (a) MMORPG players are significantly more likely to experience
      gaming-related problems relative to nonplayers, and that (b) the gaming
      motivations escapism and mechanics significantly predicted excessive gaming and
      appeared as stronger predictors than time investment in game. The findings
      support the necessity of using measures that distinguish between different types
      of online games. In addition, this study proves useful regarding the current
      discussion on establishing (online) gaming addiction as a diagnosis in future
      categorizations of psychopathology.

PMID- 22974354
TI  - Sirolimus and tacrolimus as immune prophylaxis compared to cyclosporine with or
      without methotrexate in patients undergoing allogeneic haematopoietic stem cell
      transplantation for non-malignant disorders.
AB  - For prevention of graft-versus-host disease (GVHD), treatment of 24
      haematopoietic stem cell transplantation (HSCT) patients with sirolimus and
      tacrolimus was compared to treatment of matched controls with cyclosporine-based
      regimens. The patients mainly had non-malignant disorders. Two-thirds of the
      donors were unrelated, and bone marrow was the most common source of stem cells.
      Rejection occurred in four patients in the sirolimus group and three in the
      control group. Donor chimerism for CD3, CD19 and CD33 was similar in the two
      groups. The cumulative incidence of grade II acute GVHD was 22% in the sirolimus
      patients and 17% in the controls (P=0.78). No patients developed acute GVHD of
      grades III-IV. The cumulative incidence of chronic GVHD was 25% and 37% in the
      two groups, respectively (P=0.40). Two patients in the sirolimus group developed
      Epstein-Barr virus lymphoma, and none in the controls. Side effects and toxicity
      were similar in the two groups. There was no transplant-related mortality at 5 yr
      in the sirolimus group, as opposed to 8% in the controls (P=0.47). Survival at 5
      yr was 95% and 92%. Thus, sirolimus combined with tacrolimus is a promising
      immunosuppressive regimen in HSCT, also for non-malignancies, and its efficacy
      should be confirmed in prospective clinical trials.

PMID- 22974355
TI  - Effect of daurisoline on HERG channel electrophysiological function and protein
      expression.
AB  - Daurisoline (1) is a bis-benzylisoquinoline alkaloid isolated from the rhizomes
      of Menispermum dauricum. The antiarrhythmic effect of 1 has been demonstrated in
      different experimental animals. In previous studies, daurisoline (1) prolonged
      action potential duration (APD) in a normal use-dependent manner. However, the
      electrophysiological mechanisms for 1-induced prolongation of APD have not been
      documented. In the present study, the direct effect of 1 was investigated on the
      hERG current and the expression of mRNA and protein in human embryonic kidney 293
      (HEK293) cells stably expressing the hERG channel. It was shown that 1 inhibits
      hERG current in a concentration- and voltage-dependent manner. In the presence of
      10 MUM 1, steady-state inactivation of V(1/2) was shifted negatively by 15.9 mV,
      and 1 accelerated the onset of inactivation. Blockade of hERG channels was
      dependent on channel opening. The expression and function of hERG were unchanged
      by 1 at 1 and 10 MUM, while hERG expression and the hERG current were decreased
      significantly by 1 at 30 MUM. These results indicate that 1, at concentrations
      below 30 MUM, exerts a blocking effect on hERG, but does not affect the
      expression and function of the hERG channel. This may explain the relatively
      lower risk of long QT syndrome after long-term usage.

PMID- 22974357
TI  - Fractionated stereotactic radiotherapy for cavernous haemangioma of the orbital
      apex.

PMID- 22974358
TI  - Status epilepticus in childhood.
AB  - Status epilepticus (SE) remains a life-threatening condition that afflicts both
      adults and children, and may occur at onset of epilepsy, especially in children.
      Febrile SE is the most common cause in children, while other symptomatic causes
      are less frequent compared to adults. The aetiological workup that must be
      undertaken in all cases includes neuroimaging and electroencephalography. The
      various electroencephalographic patterns seen in patients with SE along with the
      out-of-hospital treatment for SE in children and treatment strategies in cases
      that are refractory to first-line medical treatments are discussed. Medically
      induced coma may be necessary in refractory cases, although the optimal agents to
      use and degree of electroencephalographic suppression in children remain unclear.
      Neurosurgery is not a well-known treatment option that could be considered for
      refractory cases. Although the prognosis has probably improved over the years, it
      remains a potential life-threatening emergency.

PMID- 22974360
TI  - New-onset diabetes mellitus: predictive factors and impact on the outcome of
      patients undergoing liver transplantation.
AB  - Liver transplantation (LT) for hepatocellular carcinoma (HCC) is the treatment of
      choice for patients with tumor characteristics within the Milan criteria
      associated with Child B or C cirrhosis. LT provides the best cure for both the
      tumor and the cirrhosis. There have been several emerging reports that new-onset
      diabetes mellitus (NODM) after transplantation (NODAT) is one of the most
      negative predictive factors for low survival rate and related co-morbidities.
      Little is known about the onset of NODM in post-transplant patients and, overall,
      whether the pathogenesis of NODM differs from that known for the general
      population. Principally, it is still unknown whether NODAT is related to the
      primary hepatic disease, the surgical procedures, immunosuppressive treatments,
      or is it due to the donor liver. This review will focus on the identification of
      factors, in the setting of LT, which may lead to the development of NODM. Early
      prevention of these factors may abate the incidence of NODM and positively impact
      survival rate, and thus ameliorate the worsening of cardiovascular risk factors
      which usually occur after LT.

PMID- 22974361
TI  - Diabetic retinopathy screening by general practitioners using non-mydriatic
      retinography.
AB  - Diabetic retinopathy (DR) is the leading cause of visual loss in people aged 30
      to 69 years. Most authorities recommend screening of the ocular fundus to prevent
      severe visual loss. The increasing incidence of diabetes mellitus and fewer
      ophthalmologists in many countries is leading to inadequate screening.
      Establishing an adequate system for DR screening is a complex issue and
      represents a challenge for most health authorities. To alleviate the burden of DR
      screening for most health systems, some investigators have suggested that general
      practitioners (GPs) perform the initial screenings. The aim of this article was
      to review the current status of DR screening performed by GPs using non-mydriatic
      retinography. The five studies analyzed in this review indicated that after
      adequate training GPs can be effective and reliable screeners of DR using non
      mydriatic retinography. Including GPs in the screening model would be a useful
      way to alleviate the increasing demands of ophthalmic care resulting from the
      increased prevalence of diabetes mellitus. In addition, GPs would have full
      control of the diabetic process, which could bolster their motivation and
      confidence in other areas of diabetes care and medical practice.

PMID- 22974362
TI  - Stable radical trianions from reversibly formed sigma-dimers of
      selenadiazoloquinolones studied by in situ EPR/UV-vis spectroelectrochemistry and
      quantum chemical calculations.
AB  - The redox behavior of the series of 7-substituted 6-oxo-6,9
      dihydro[1,2,5]selenadiazolo[3,4-h]quinolines and 8-substituted 9-oxo-6,9
      dihydro[1,2,5]selenadiazolo[3,4-f]quinolines with R(7), R(8) = H, COOC(2)H(5),
      COOCH(3), COOH, COCH(3), and CN has been studied by in situ EPR and EPR/UV-vis
      spectroelectrochemistry in dimethylsulfoxide. All selenadiazoloquinolones undergo
      a one-electron reduction process to form the corresponding radical anions. Their
      stability strongly depends on substitution at the nitrogen atom of the 4-pyridone
      ring. The primary generated radical anions from N-ethyl-substituted quinolones
      are stable, whereas for the quinolones with imino hydrogen, the initial radical
      anions rapidly dimerize to produce unusually stable sigma-dimer (sigma-dimer)
      dianions. These are reversibly oxidized to the initial compounds at potentials
      considerably less negative than the original reduction process in the back
      voltammetric scan. The dimer dianion can be further reduced to the stable
      paramagnetic dimer radical trianion in the region of the second reversible
      reduction step. The proposed complex reaction mechanism was confirmed by in situ
      EPR/UV-vis cyclovoltammetric experiments. The site of the dimerization in the
      sigma-dimer and the mapping of the unpaired spin density both for radical anions
      and sigma-dimer radical trianions with unusual unpaired spin distribution have
      been assigned by means of density functional theory calculations.

PMID- 22974363
TI  - A new sesquiterpene glucoside from Nicotiana rustica L.
AB  - A new compound, rel-2R,5S,9S,10R,11R,12-trihydroxy-6(7)-spirovetiven-8-one-9- O
      beta-D-glucopyranoside (1), along with a known spirovetiven glucoside (2), was
      isolated from the leaves of Nicotiana rustica L. The structure of compound (1)
      was elucidated on the basis of spectroscopic data.

PMID- 22974365
TI  - Scoping the impact of the national child measurement programme feedback on the
      child obesity pathway: study protocol.
AB  - BACKGROUND: The National Child Measurement Programme was established to measure
      the height and weight of children at primary school in England and provides
      parents with feedback about their child's weight status. In this study we will
      evaluate the impact of the National Child Measurement Programme feedback on
      parental risk perceptions of overweight, lifestyle behaviour and health service
      use. METHODS: The study will be a prospective cohort study of parents of children
      enrolled in the National Child Measurement Programme and key service providers
      from 5 primary care trusts (administrative bodies responsible for providing
      primary and secondary care services). We will conduct baseline questionnaires,
      followed by provision of weight feedback and 3 follow up questionnaires over the
      course of a year. Questionnaires will measure change in parental risk perception
      of overweight, health behaviours and health service use. Qualitative interviews
      will be used to identify barriers and facilitators to change. This study will
      produce preliminary data on National Health Service costs associated with weight
      feedback and determine which feedback approach (letter and letter plus telephone)
      is more effective. DISCUSSION: This study will provide the first large scale
      evaluation of the National Child Measurement Programme feedback. Findings from
      this evaluation will inform future planning of the National Child Measurement
      Programme.

PMID- 22974364
TI  - Self-assembly of filamentous amelogenin requires calcium and phosphate: from
      dimers via nanoribbons to fibrils.
AB  - Enamel matrix self-assembly has long been suggested as the driving force behind
      aligned nanofibrous hydroxyapatite formation. We tested if amelogenin, the main
      enamel matrix protein, can self-assemble into ribbon-like structures in
      physiologic solutions. Ribbons 17 nm wide were observed to grow several
      micrometers in length, requiring calcium, phosphate, and pH 4.0-6.0. The pH range
      suggests that the formation of ion bridges through protonated histidine residues
      is essential to self-assembly, supported by a statistical analysis of 212
      phosphate-binding proteins predicting 12 phosphate-binding histidines.
      Thermophoretic analysis verified the importance of calcium and phosphate in self
      assembly. X-ray scattering characterized amelogenin dimers with dimensions
      fitting the cross-section of the amelogenin ribbon, leading to the hypothesis
      that antiparallel dimers are the building blocks of the ribbons. Over 5-7 days,
      ribbons self-organized into bundles composed of aligned ribbons mimicking the
      structure of enamel crystallites in enamel rods. These observations confirm
      reports of filamentous organic components in developing enamel and provide a new
      model for matrix-templated enamel mineralization.

PMID- 22974366
TI  - Metal containing chloroquinolines: beyond hit and miss antimalarial efficacy to
      solid science.
AB  - Research into metal complexes of known antimalarial drugs have been known for 30
      years. Initial exploration into this field was fairly slow and largely limited to
      the synthesis of the complexes and reporting of antiplasmodial efficacy. In the
      last five years this approach has shifted substantially. Increasingly papers
      dealing with the mechanism of action, the speciation of the complexes, and other
      aspects of the interaction of these complexes in the biological system are
      appearing. This shift in focus indicates that the application of bioinorganic and
      bioorganometallic chemistry are beginning to mature into well established fields
      of research. This paper tracks the development of this field from the humble
      beginnings to the development of a substantial body of research.

PMID- 22974367
TI  - Functional PLGA NPs for oral drug delivery: recent strategies and developments.
AB  - This article presents the potential of PLGA nanoparticles for the oral
      administration of drugs. Different strategies are used to improve oral absorption
      of these nanoparticles. These strategies are based on modification of
      nanoparticle surface properties. They can be achieved either by coating the
      nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or
      surfactants, or by incorporating biodegradable copolymers containing a
      hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates,
      lectins, lecithins, bile salts and RGD molecules are employed for this purpose.
      Of especial interest are nanoparticles production methods and, in order to
      improve oral bioavailability, the mechanism of each additive.

PMID- 22974368
TI  - Eps homology domain endosomal transport proteins differentially localize to the
      neuromuscular junction.
AB  - BACKGROUND: Recycling of endosomes is important for trafficking and maintenance
      of proteins at the neuromuscular junction (NMJ). We have previously shown high
      expression of the endocytic recycling regulator Eps15 homology domain-containing
      (EHD)1 proteinin the Torpedo californica electric organ, a model tissue for
      investigating a cholinergic synapse. In this study, we investigated the
      localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal
      muscle, and assessed the morphological changes in EHD1-/- NMJs. METHODS:
      Localization of the candidate NMJ protein EHD1 was assessed by confocal
      microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene
      transfer and immunolabeling. The potential function of EHD1 was assessed by
      specific force measurement and alpha-bungarotoxin-based endplate morphology
      mapping in EHD1-/- mouse skeletal muscle. RESULTS: Endogenous EHD1 localized to
      primary synaptic clefts of murine NMJ, and this localization was confirmed by
      expression of recombinant green fluorescent protein labeled-EHD1 in murine
      skeletal muscle in vivo. EHD1-/- mouse skeletal muscle had normal histology and
      NMJ morphology, and normal specific force generation during muscle contraction.
      The EHD 1-4 proteins showed differential localization in skeletal muscle: EHD2 to
      muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions
      and to primary synaptic clefts, but at lower levels than EHD1. Additionally,
      specific antibodies raised against mammalian EHD1-4 recognized proteins of the
      expected mass in the T. californica electric organ. Finally, we found that EHD4
      expression was more abundant in EHD1-/- mouse skeletal muscle than in wild-type
      skeletal muscle. CONCLUSION: EHD1 and EHD4 localize to the primary synaptic
      clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function
      in EHD1-/- muscle may be due to functional compensation by other EHD paralogs.

PMID- 22974369
TI  - Investigation of the 1064 nm Q-switched Nd:YAG laser on collagen expression in an
      animal model.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to evaluate the changes
      of collagen expression and its possible molecular mechanism in the rat skin
      induced by 1064 nm Q-switched Nd:YAG laser treatments. METHODS: The dorsal skin
      of Sprague-Dawley (SD) rats was irradiated with the 1064 nm laser at fluences of
      0, 0.6, 1.5, and 2.5 J/cm2, respectively. Then biochemical analysis was used to
      quantify hydroxyproline content in the skin. The mRNA expressions of procollagen,
      matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases
      (TIMPs) were analyzed by using reverse transcription-polymerase chain reaction
      (RT-PCR). The activities of mitogen-activated protein kinase (MAPK) family
      members were detected by Western blot analysis. RESULTS: The 1064 nm laser
      treatments led to a marked increase in collagen content in a dose-dependent
      manner. The expression of types I and III collagen, TIMP1 and TIMP2, in the skin
      was markedly upregulated, whereas the expression of MMP2 and MMP3 was
      significantly decreased after laser treatments. Both extracellular signal-related
      kinase (Erk)1/2 and JNK MAPK pathways were activated by the 1064 nm laser
      irradiation. CONCLUSIONS: The 1064 nm laser irradiation could markedly increase
      collagen synthesis and inhibit collagen degradation. The activation of Erk1/2 and
      JNK MAPK seems to play a role in collagen production in the rat skin, induced by
      the 1064 nm laser.

PMID- 22974370
TI  - Effects of low-level laser therapy as an adjunct to standard therapy in acute
      pericoronitis, and its impact on oral health-related quality of life.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of low-level
      laser therapy (LLLT) as an adjunct to standard therapy in acute pericoronitis.
      METHODS: Eighty acute pericoronitis patients were randomly assigned to one of
      four LLLT groups: (neodymium:yttrium-aluminum garnet [Nd:YAG] 1064-nm: n=20, 8
      J/cm2, 0.25 W, 10 Hz, 10 sec; 808-nm diode: n=20, 8 J/cm2, 0.25 W, continuous
      mode, 10 sec; 660-nm diode: n=20, 8 J/cm2, 0.04 W, continuous mode, 60 sec; or a
      placebo laser control group: n=20). After standard treatment, LLLT or a placebo
      laser were applied to the treatment area at a distance of 1 cm from the buccal
      site. Interincisal opening, pain perception, and oral health-related quality of
      life (OHRQoL) were evaluated at baseline, 24 h, and 7 days after laser
      application. The data were analyzed by the one-way ANOVA test. RESULTS: We found
      that the trismus and the OHRQoL in the Nd:YAG and the 808-nm diode groups were
      significantly improved when compared with the 660-nm diode and control groups at
      24 h (p<0.05). No statistically significant differences were detected on day 7
      among the groups with regard to any of the parameters evaluated. CONCLUSIONS: The
      results demonstrate that both the 1064-nm Nd:YAG and the 808-nm diode lasers were
      effective in improving trismus and OHRQoL in acute pericoronitis. Taking into
      account the limitations of this study, we conclude that the 1064-nm Nd:YAG laser
      has biostimulatory effects and improves OHRQoL, making it suitable for LLLT.

PMID- 22974359
TI  - Regulation of insulin synthesis and secretion and pancreatic Beta-cell
      dysfunction in diabetes.
AB  - Pancreatic beta-cell dysfunction plays an important role in the pathogenesis of
      both type 1 and type 2 diabetes. Insulin, which is produced in beta-cells, is a
      critical regulator of metabolism. Insulin is synthesized as preproinsulin and
      processed to proinsulin. Proinsulin is then converted to insulin and C-peptide
      and stored in secretary granules awaiting release on demand. Insulin synthesis is
      regulated at both the transcriptional and translational level. The cis-acting
      sequences within the 5' flanking region and trans-activators including paired box
      gene 6 (PAX6), pancreatic and duodenal homeobox- 1(PDX-1), MafA, and beta
      2/Neurogenic differentiation 1 (NeuroD1) regulate insulin transcription, while
      the stability of preproinsulin mRNA and its untranslated regions control protein
      translation. Insulin secretion involves a sequence of events in beta-cells that
      lead to fusion of secretory granules with the plasma membrane. Insulin is
      secreted primarily in response to glucose, while other nutrients such as free
      fatty acids and amino acids can augment glucose-induced insulin secretion. In
      addition, various hormones, such as melatonin, estrogen, leptin, growth hormone,
      and glucagon like peptide-1 also regulate insulin secretion. Thus, the beta-cell
      is a metabolic hub in the body, connecting nutrient metabolism and the endocrine
      system. Although an increase in intracellular [Ca2+] is the primary insulin
      secretary signal, cAMP signaling- dependent mechanisms are also critical in the
      regulation of insulin secretion. This article reviews current knowledge on how
      beta-cells synthesize and secrete insulin. In addition, this review presents
      evidence that genetic and environmental factors can lead to hyperglycemia,
      dyslipidemia, inflammation, and autoimmunity, resulting in beta-cell dysfunction,
      thereby triggering the pathogenesis of diabetes.

PMID- 22974372
TI  - Ligation of the intersphincteric fistula tract in low transsphincteric fistulae:
      a new technique to avoid fistulotomy.
AB  - AIM:   To date fistulotomy is still the treatment of choice for patients with a
      transsphincteric fistula passing through the lower third of the external anal
      sphincter, because it is a simple, effective and safe procedure with a minimal
      risk of incontinence. However, data suggest that the risk of impaired continence
      following division of the lower third of the external anal sphincter is not
      insignificant, especially in female patients with an anterior fistula and
      patients with diminished anal sphincter function. It has been shown that ligation
      of the intersphincteric fistula tract (LIFT) is a promising sphincter-preserving
      technique. Therefore, we questioned whether LIFT could replace fistulotomy in
      patients with a low transsphincteric fistula. METHOD: A consecutive series of 22
      patients with a low transsphincteric fistula of cryptoglandular origin underwent
      LIFT. Continence scores were determined using the Rockwood Fecal Incontinence
      Severity Index. RESULTS:   Median follow-up was 19.5months. Primary healing was
      observed in 18 (82%) patients. In the four patients without primary healing, the
      transsphincteric fistula was converted into an intersphincteric fistula. These
      patients underwent subsequent fistulotomy with preservation of the external anal
      sphincter. The overall healing rate was 100%. Six months after surgery, the
      median incontinence score was not changed significantly. CONCLUSION:   Low
      transsphincteric fistulae can be treated successfully by LIFT, without affecting
      faecal continence. Division of the lower part of the external anal sphincter is
      no longer necessary in the treatment of low transsphincteric fistulae, which is
      essential for patients with compromised anal sphincters.

PMID- 22974371
TI  - Emodin as an effective agent in targeting cancer stem-like side population cells
      of gallbladder carcinoma.
AB  - Side population (SP) cells are previously identified from bone marrow based on
      their capacity to efflux of the fluorescent dye Hoechst 33342. Recent studies
      demonstrate that SP cells isolated from various cancer cell lines and primary
      tumors possess stem-cell-like properties. Thus, targeting tumor SP cells may
      provide new strategies for treatment in clinic. We previously showed that 1,3,8
      trihydroxy-6-methylanthraquinone (emodin), a reactive oxygen species (ROS)
      generator, enhanced sensitivity of gallbladder cancer SGC-996 cells to cisplatin
      (CDDP) via generation of ROS and downregulation of multidrug-resistance
      associated protein 1 (MRP1). To determine whether emodin also acts effectively on
      cancer stem cells of gallbladder carcinoma, we use SP cells as a model of cancer
      stem-cell-like cells. Here, we found that emodin, via ROS-related mechanism and
      suppressing the function of ATP-binding cassette super-family G member (ABCG2),
      which is known to be associated with Hoechst dye efflux activity of SP cells, not
      only reduced the ratio, inhibited clone formation, and eliminated sphere
      formation of SP cells effectively, but also promoted obviously the intracellular
      accumulation of doxorubicin, the main substrate of the efflux pump ABCG2. In
      addition, emodin could sensitize CDDP, via inhibition of expression of ABCG2, to
      overcome chemoresistance of SP cells. Importantly, similar to the experiment in
      vitro, emodin/CDDP co-treatment in vivo suppressed the tumor growth derived from
      SP cells through downregulating ABCG2 expression. Our results suggest that emodin
      is an effective agent targeting cancer stem-like SP cells of gallbladder
      carcinoma, either alone or acts as a chemotherapy enhancer.

PMID- 22974373
TI  - Economic evaluation of task-shifting approaches to the dispensing of anti
      retroviral therapy.
AB  - BACKGROUND: A scarcity of human resources for health has been identified as one
      of the primary constraints to the scale-up of the provision of Anti-Retroviral
      Treatment (ART). In South Africa there is a particularly severe lack of
      pharmacists. The study aims to compare two task-shifting approaches to the
      dispensing of ART: Indirectly Supervised Pharmacist's Assistants (ISPA) and Nurse
      based pharmaceutical care models against the standard of care which involves a
      pharmacist dispensing ART. METHODS: A cross-sectional mixed methods study design
      was used. Patient exit interviews, time and motion studies, expert interviews and
      staff costs were used to conduct a costing from the societal perspective. Six
      facilities were sampled in the Western Cape province of South Africa, and 230
      patient interviews conducted. RESULTS: The ISPA model was found to be the least
      costly task-shifting pharmaceutical model. However, patients preferred receiving
      medication from the nurse. This related to a fear of stigma and being identified
      by virtue of receiving ART at the pharmacy. CONCLUSIONS: While these models are
      not mutually exclusive, and a variety of pharmaceutical care models will be
      necessary for scale up, it is useful to consider the impact of implementing these
      models on the provider, patient access to treatment and difficulties in
      implementation.

PMID- 22974374
TI  - Chronic N-amended soils exhibit an altered bacterial community structure in
      Harvard Forest, MA, USA.
AB  - At the Harvard Forest, Petersham, MA, the impact of 20 years of annual ammonium
      nitrate application to the mixed hardwood stand on soil bacterial communities was
      studied using 16S rRNA genes pyrosequencing. Amplification of 16S rRNA genes was
      done using DNA extracted from 30 soil samples (three treatments * two horizons *
      five subplots) collected from untreated (control), low N-amended (50 kg ha(-1)
      year(-1)) and high N-amended (150 kg ha(-1) year(-1)) plots. A total of 1.3
      million sequences were processed using qiime. Although Acidobacteria represented
      the most abundant phylum based on the number of sequences, Proteobacteria were
      the most diverse in terms of operational taxonomic units (OTUs). UniFrac analyses
      revealed that the bacterial communities differed significantly among soil
      horizons and treatments. Microsite variability among the five subplots was also
      evident. Nonmetric multidimensional scaling ordination of normalized OTU data
      followed by permutational manova further confirmed these observations. Richness
      indicators and indicator species analyses revealed higher bacterial diversity
      associated with N amendment. Differences in bacterial diversity and community
      composition associated with the N treatments were also observed at lower
      phylogenetic levels. Only 28-35% of the 6 936 total OTUs identified were common
      to three treatments, while the rest were specific to one treatment or common to
      two.

PMID- 22974375
TI  - Complexes of 2,5-bis(alpha-pyridyl)pyrrolate with Pd(II) and Pt(II): a
      monoanionic iso-pi-electron ligand analog of terpyridine.
AB  - Palladium and platinum metal complexes of 2,5-bis(alpha-pyridyl)pyrrolate (PDP)
      are reported and characterized by spectroscopic methods, single-crystal X-ray
      diffraction, and elemental analysis. The single-crystal X-ray structures of these
      complexes exhibit structural features indicative of significant pi-backbonding.
      To illustrate the effect, bond lengths are statistically compared to unmetalated
      PDP and to a previously reported Zn(II) complex that exhibits no backbonding.
      Density functional theory calculations are used to aid understanding of the
      electronic structural basis of the observed phenomena.

PMID- 22974376
TI  - Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe,
      North-east Brazil.
AB  - OBJECTIVES: To estimate, by neonatal screening, the birth prevalence of
      congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to
      investigate the clinical features of affected infants. METHODS: Dried blood spot
      specimens obtained from 15 204 neonates were assayed for the presence of anti-T.
      gondii IgM antibodies. Duplicate retesting was done in infants with positive and
      borderline results. Confirmatory testing in peripheral blood samples consisted of
      testing for anti-T. gondii IgG and IgM in infants and mothers. Those with
      possible congenital toxoplasmosis were evaluated and followed up to a median age
      of 20 months. Congenital infection was confirmed in the presence of persisting
      anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed
      infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1
      year. RESULTS:   Fifty-three infants had detectable IgM in dried blood spot
      specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed
      follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis,
      resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4-8.0].
      Four infants (67%) showed signs of congenital toxoplasmosis in their first year
      of life; three (75%) had retinochoroidal scars, and one had cerebral
      calcifications. Two infants remained asymptomatic until 20 months of age.
      CONCLUSIONS: The birth prevalence of congenital toxoplasmosis is high in the
      Brazilian state of Sergipe, with most of the infants showing ocular lesions.
      Preventive measures are strongly warranted.

PMID- 22974377
TI  - Correcting transit time distributions in coarse MODFLOW-MODPATH models.
AB  - In low to medium resolution MODFLOW models, the area occupied by sink cells often
      far exceeds the surface area of the streams they represent. As a result, MODPATH
      will calculate inaccurate particle traces and transit times. A frequency
      distribution of transit times for a watershed will also be in error. Such a
      distribution is used to assess the long-term impact of nonpoint source pollution
      on surface waters and wells. Although the inaccuracies for individual particles
      can only be avoided by increased model grid resolution or other advanced modeling
      techniques, the frequency distribution can be improved by scaling the particle
      transit times by an adjustment factor during post-processing.

PMID- 22974378
TI  - Commentary: we know how much mohs is done, but is it appropriate?

PMID- 22974379
TI  - Commentary: improved detection of nonpigmented skin tumors.

PMID- 22974380
TI  - Letter: re: February special issue on aesthetic scales.

PMID- 22974382
TI  - Letter: autologous fat grafting and platelet-rich plasma for treatment of facial
      contour defects.

PMID- 22974383
TI  - Letter: "blue pseudo-veil sign"--a new dermoscopic term?

PMID- 22974384
TI  - Letter: letter regarding autologous fibroblast culture in the repair of aging
      skin.

PMID- 22974386
TI  - Human interferon-alpha increases the cytotoxic effect of CD56(+) cord blood
      derived cytokine-induced killer cells on human B-acute lymphoblastic leukemia
      cell lines.
AB  - BACKGROUND AIMS: Cytokine-induced killer (CIK) cells may represent a promising
      immunotherapy for the treatment of children with relapsing B-lineage acute
      lymphoblastic leukemia (B-ALL) following hematopoietic stem cell transplantation
      (HSCT). Therefore, we investigated the possibility of combining adoptive
      immunotherapy with CIK cells and human interferon-alpha (hIFN-alpha) in order to
      potentiate the cytotoxicity of CIK cells against B-ALL. METHODS: Cord blood-
      derived CIK (CB-CIK) cells were differentiated, stimulated with phosphate
      buffered saline (PBS) or hIFN-alpha, and tested for cytotoxic activity. We tested
      the anti-leukemic and graft-versus-host disease (GvHD) effects of CB-CIK cells in
      a human xenograft NOD/SCID/gammac(-) (NSG) mouse model. RESULTS: Bulk CB-CIK
      cells showed very moderate cytotoxic activity while the subpopulation of CD56(+)
      CB-CIK cells showed significant cytotoxic activity against B-ALL cells. hIFN
      alpha significantly augmented the cytotoxicity of CD56(+)CB-CIK cells in vitro
      and induced signal transducer and activator of transcription-1 (STAT1)
      phosphorylation. In addition, CD56(+)CB-CIK cells could delay mouse mortality
      significantly in vivo, and this effect was enhanced significantly by hIFN-alpha
      (P = 0.022). Furthermore, unlike CB mononuclear cells or peripheral blood
      mononuclear cells (PBMC), CD56(+)CB-CIK cells, alone or stimulated with hIFN
      alpha, caused either no GvHD or mild GvHD, respectively, when injected into
      sublethally irradiated NSG mice. CONCLUSIONS: CD56(+)CB-CIK cells are effective
      cytotoxic agents against human B-ALL cell lines in vitro and possess anti
      leukemic activity that is potentiated by hIFN-alpha in an NSG mouse model in
      vivo. These pre-clinical data support the testing of this immunotherapeutic
      approach in the clinic for the treatment of B-ALL.

PMID- 22974387
TI  - Electronic spectra of structurally deformed lutein.
AB  - Quantum chemical calculations have been employed for the investigation of the
      lowest excited electronic states of lutein, with particular reference to its
      function within light harvesting antenna complexes of higher plants. Through
      comparative analysis obtained by using different methods based on gas-phase
      calculations of the spectra, it was determined that variations in the lengths of
      the long C-C valence bonds and the dihedral angles of the polyene chain are the
      dominant factors in determining the spectral properties of Lut 1 and Lut 2
      corresponding to the deformed lutein molecules taken from crystallographic data
      of the major pigment-protein complex of photosystem II. By MNDO-CAS-CI method, it
      was determined that the two singlet B(u) states of lutein (nominally 1B(u)(-)*
      and 1B(u)(+)) arise as a result of mixing of the canonical 1B(u)(-) and 1B(u)(+)
      states of the all-trans polyene due to the presence of the ending rings in
      lutein. The 1B(u)(-)* state of lutein is optically allowed, while the 1B(u)(-) of
      a pure all-trans polyene chain is optically forbidden. As demonstrated, the B(u)
      states are much more sensitive to minor distortions of the conjugated chain due
      to mixing of the canonical states, resulting in states of poorly defined particle
      hole symmetry. Conversely, the A(g) states are relatively robust with respect to
      geometric distortion, and their respective inversion and particle-hole symmetries
      remain relatively well-defined.

PMID- 22974388
TI  - Racing with nature: artificial nanomachines that keep running on light, both left
      and right.
AB  - Nature's molecular motors and nanomachines perform marvelous tasks, especially on
      the level of single cells. Can artificial ones compete? In this issue, You et al.
      demonstrate a photon-driven molecular machine where switching the color of the
      light switches the direction of motion of the molecular motor. While having
      inferior performance characteristics, this novel motor may become the forerunner
      of a new generation of sophisticated and practical competitors with Nature's
      ancient, but highly important, nanomachines.

PMID- 22974389
TI  - Corneal thickness after overnight wear of an intraocular pressure fluctuation
      contact lens sensor.
AB  - PURPOSE: To assess the effect of overnight wear of a contact lens-based sensor
      (CLS) for monitoring of 24-hr intraocular pressure (IOP) fluctuations on central
      corneal thickness (CCT). MATERIALS AND METHODS:  Changes in the CCT, mid
      peripheral corneal thickness and central corneal radius (CCR) during overnight
      CLS wear in 20 eligible patients with ocular hypertension or established glaucoma
      were prospectively studied using ultrasound pachymetry and topography. Corneal
      thickness and CCR changes were evaluated from pre-to-postsleep, with the fellow
      eye as control. Paired t-test or Wilcoxon signed-rank test was used as
      appropriate and with alpha = 0.05. Relationship between the IOP profile recorded
      by the CLS and the pre-to-postsleep corneal thickness differences was assessed
      using the Spearman correlation coefficient. RESULTS: After CLS wear, mean CCT had
      changed from 523 to 537 MUm (p = 0.015) in the study eye and from 518 to 522 (p =
      0.206) in the fellow eye (n = 15). There was no difference in CCT change between
      eyes (p = 0.075). There were no statistically significant changes in horizontal
      or vertical CCR in either eye (p > 0.05 for all). No correlation was found
      between the pre-to-postsleep differences in the CLS signal and the pre-to
      postsleep differences in ultrasound CCT measurements (p = 0.974). CONCLUSION: The
      continuous IOP monitoring does not appear to be affected by differences in
      corneal thickness that occur during overnight CLS wear, although the CLS did
      induce some corneal swelling. This effect was not statistically significantly
      different from the control eye and does not seem to influence the CLS IOP
      profile.

PMID- 22974390
TI  - Molecular pathology in therapeutics: where are we now, and where are we going?

PMID- 22974391
TI  - Making the most of pathological specimens: molecular diagnosis in formalin-fixed,
      paraffin embedded tissue.
AB  - The development of commercial reagents designed specifically for use with
      formalin-fixed paraffin-embedded (FFPE) tissue has unlocked the diagnostic
      potential of this prolific resource. The availability of archival FFPE tissue and
      tissue from current patients make it an ideal resource for molecular testing.
      Despite its stability and ability to preserve morphological information, FFPE
      provides a number of technical challenges to the study of biomolecules. In
      particular, the cross-linking and processing present problems in the extraction
      and isolation of DNA, RNA and protein and affect their use in downstream
      analysis. Here we will discuss some of the problems of FFPE tissue, how they can
      be overcome and how FFPE material can be used within clinical molecular
      diagnostics.

PMID- 22974392
TI  - Molecular classification and drug response prediction in cancer.
AB  - Molecular profiling of cancers can potentially yield novel gene markers of
      therapeutic prediction, which would aid our ability to tailor targeted therapy
      regimens specific to each patient. Public data from gene expression profiling may
      yield clues as to what oncogenic signaling pathways are deregulated in cancers,
      and what drugs may effectively counteract the aberrant gene regulation patterns
      observed. Data are also available on panels of cancer cell lines, which have been
      both profiled at the gene expression level and extensively characterized for drug
      responses, allowing us to identify gene-to-drug correlations. Profiling tumors
      from patients undergoing adjuvant or neoadjuvant drug treatment can also yield
      markers of therapeutic response. In this review, we will examine recent studies
      aimed at our eventually being able to use the molecular profile of a tumor to
      predict drug response. The profiling data from these studies is publicly
      available, and can be re-examined by researchers with different questions in
      mind, offering us a large number of biomarker candidates that could potentially
      be tested in the clinical setting.

PMID- 22974393
TI  - Proteomic classification of breast cancer.
AB  - Being a significant health problem that affects patients in various age groups,
      breast cancer has been extensively studied to date. Recently, molecular breast
      cancer classification has advanced significantly with the availability of genomic
      profiling technologies. Proteomic technologies have also advanced from
      traditional protein assays including enzyme-linked immunosorbent assay,
      immunoblotting and immunohistochemistry to more comprehensive approaches
      including mass spectrometry and reverse phase protein lysate arrays (RPPA). The
      purpose of this manuscript is to review the current protein markers that
      influence breast cancer prediction and prognosis and to focus on novel advances
      in proteomic classification of breast cancer.

PMID- 22974394
TI  - Targeting basal-like breast cancers.
AB  - Basal-like breast tumors and triple negative breast tumors are high-risk breast
      cancers that typically carry the poorest prognoses compared with HR (Hormone
      Receptor)-positive tumors and HER2 (Human Epidermal growth factor Receptor 2)
      amplified tumors for known therapies. These subsets of breast cancers exhibit
      aggressive clinical behavior, pushing margins of invasion, poor clinical outcome,
      and derive limited benefit from current therapy. This clinical situation is
      contributed and further aggravated by their less known biology, lack of obvious
      molecular targets, absence of favorable biomarkers, and their limited response to
      single-drug therapy. In 2010, Oakman et al., remarked that current therapy fails
      to curtail the innate aggressive behavior of TNBC (Triple Negative Breast Cancer)
      in the majority of patients. The poor prognosis coupled with a lack of targeted
      use of therapies is responsible for the high mortality in this subtype. The
      present review will examine the existing literature and scrutinize the
      difficulties that have, to date, limited the understanding of the biology of
      these tumor cells, and provide a rationale for the development of the concept of
      combining subtype-specific and pathway-specific drug targets for the therapeutic
      intervention of the disease.

PMID- 22974396
TI  - Animal modeling of cancer pathology and studying tumor response to therapy.
AB  - Animal models of human cancer have evolved in attempts to capture the complexity
      of the human disease. They encompass two broad types of model, namely those in
      which the tumor arises in situ and those in which cancer cells or tissue are
      transplanted. Currently human tumor xenografts are the most widely used model to
      help predict antitumor efficacy in a preclinical setting and xenograft results
      for certain disease types such as ovarian cancer and non-small cell lung cancer
      correlate well with clinical activity if the models are used under appropriate
      conditions. The genetically engineered mouse (GEM) models allow study of the
      effects of targeted inhibitors against defined molecular targets. These are
      becoming increasingly sophisticated to recapitulate the progression of tissue
      specific molecular changes found within individual cancers. Non-germline GEM
      models possess the ability to study the impact of specific cancer genes without
      some of the limitations inherent in traditional GEM models. While rodents,
      particularly mice, have been the animal host most frequently used, there is
      increasing recognition of the value of using larger species especially dogs in
      the veterinary oncology setting. These have successfully modelled aspects of
      selected human cancers such as osteosarcoma, GIST and prostate cancer.
      Individually, these models have relative strengths and weaknesses in mimicking
      the human disease and appropriately reflecting its cellular and molecular
      pathology. This review will seek to address where these models can be best used
      to help predict response to therapeutics.

PMID- 22974395
TI  - Tissue-based approaches to study pharmacodynamic endpoints in early phase
      oncology clinical trials.
AB  - Anti-cancer clinical drug development is currently costly and slow with a high
      attrition rate. There is thus an urgent and unmet need to integrate
      pharmacodynamic biomarkers into early phase clinical trials in the framework
      provided by the "pharmacologic audit trail" in order to overcome this challenge.
      This review discusses the rationale, advantages and disadvantages, as well as the
      practical considerations of various tissue-based approaches to perform
      pharmacodynamic studies in early phase oncology clinical trials using case
      histories of molecular targeting agents such as PI3K, m-TOR, HSP90, HDAC and PARP
      inhibitors. These approaches include the use of normal "surrogate" tissues such
      as peripheral blood mononuclear cells, platelet-rich plasma, plucked hair
      follicles, skin biopsies, plasma-based endocrine assays, proteomics, metabolomics
      and circulating endothelial cells. In addition, the review discusses the use of
      neoplastic tissues including tumor biopsies, circulating tumor DNA and tumor
      cells and metabolomic approaches. The utilization of these tissues and technology
      platforms to study biomarkers will help accelerate the development of molecularly
      targeted agents for the treatment of cancer.

PMID- 22974397
TI  - Molecular pathology in neurodegenerative diseases.
AB  - Neurodegenerative diseases are increasing in prevalence in many countries as the
      average age of their populations increases, since many of these disorders occur
      more frequently in elderly individuals, placing an increasing burden on
      healthcare resources. Most neurodegenerative disorders are associated with
      accumulations of abnormal proteins in the central nervous system (CNS), which
      result in neuronal degeneration and ultimately neuronal death. Recent
      developments in molecular pathology and genetics have allowed the identification
      of the abnormal proteins involved in many neurodegenerative disorders and the
      genes that encode these proteins. This has led to a fuller understanding of the
      mechanisms of many of these diseases, but this has not so far been accompanied by
      major improvements in diagnostic tests or treatments for these disorders. Prion
      diseases are rare neurodegenerative disorders that are associated with the
      accumulation of a misfolded host protein, the prion protein, in the CNS. Prion
      diseases have been considered as a paradigm for protein misfolding diseases, but
      there are significant differences between prion diseases and other
      neurodegenerative disorders, not least in the transmissible nature of prion
      diseases. In this review we give an overview of the wide range of
      neurodegenerative diseases that affect humans, and compare the molecular
      pathology of prion diseases with other neurodegenerative diseases. The concept of
      proteinopathy as a common mechanism in neurodegenerative disorders is explored,
      and we highlight the improvements in diagnosis and management required to improve
      our treatment of these devastating conditions.

PMID- 22974398
TI  - Engineering simulations for cancer systems biology.
AB  - Computer simulation can be used to inform in vivo and in vitro experimentation,
      enabling rapid, low-cost hypothesis generation and directing experimental design
      in order to test those hypotheses. In this way, in silico models become a
      scientific instrument for investigation, and so should be developed to high
      standards, be carefully calibrated and their findings presented in such that they
      may be reproduced. Here, we outline a framework that supports developing
      simulations as scientific instruments, and we select cancer systems biology as an
      exemplar domain, with a particular focus on cellular signalling models. We
      consider the challenges of lack of data, incomplete knowledge and modelling in
      the context of a rapidly changing knowledge base. Our framework comprises a
      process to clearly separate scientific and engineering concerns in model and
      simulation development, and an argumentation approach to documenting models for
      rigorous way of recording assumptions and knowledge gaps. We propose interactive,
      dynamic visualisation tools to enable the biological community to interact with
      cellular signalling models directly for experimental design. There is a mismatch
      in scale between these cellular models and tissue structures that are affected by
      tumours, and bridging this gap requires substantial computational resource. We
      present concurrent programming as a technology to link scales without losing
      important details through model simplification. We discuss the value of combining
      this technology, interactive visualisation, argumentation and model separation to
      support development of multi-scale models that represent biologically plausible
      cells arranged in biologically plausible structures that model cell behaviour,
      interactions and response to therapeutic interventions.

PMID- 22974399
TI  - Long non-coding RNAs involved in cancer development and cell fate determination.
AB  - The possible physiological significance of long non-coding RNAs (lncRNAs) has
      only recently been recognized. Technical innovations such as the super high
      resolution tiling array and deep sequencing technology have indicated their
      importance. It has been proposed that lncRNAs such as HOTAIR are involved in the
      recruitment of chromatin modifiers to the target genes. The lncRNA ANRIL has been
      reported to be associated with a Polycomb complex, recruiting it to the target
      gene INK4 locus where it suppresses transcription via histone modification. Other
      lncRNAs such as Kcnq1ot1, AIR and Xist have also been found to recruit chromatin
      modifiers to their target loci. In this review, we discuss the function of
      lncRNAs such as HOTAIR, ANRIL, Kcnq1ot1, and Xist which recruit chromatin
      modifiers to target genes and discuss their involvement in cancer development and
      aggressiveness, and other cell fate determination.

PMID- 22974400
TI  - Recent developments in antimalarial natural products isolated from medicinal
      plants.
AB  - Malaria is an infectious disease causing almost one million deaths each year.
      There is an urgent need for discovery of new antimalarial compounds. Natural
      products have been the single most productive source of leads for the development
      of drugs, because of their great variety of chemical structures. This review
      covers studies on antimalarial natural products isolated from plants, published
      from January 2010 until April 2012. A total of 171 structures comprising
      alkaloids, terpenoids, phenolics and other metabolites are listed in this review,
      including information on their antiplasmodial and cytotoxic activity.

PMID- 22974401
TI  - Isolation of the volatile fraction from Apium graveolens L. (Apiaceae) by
      supercritical carbon dioxide extraction and hydrodistillation: chemical
      composition and antifungal activity.
AB  - Apium graveolens L. (wild celery), belonging to the family of Apiaceae, is a
      scaposus hemicryptophyte. Instead, the cultivate plant is an annual or biennial
      herb widely used as a spice and seasoning in food. A broad range of biological
      activities have been attributed to A. graveolens. These include antimicrobial
      activity, larvicidal activity, hepatoprotective activity, nematicidal and
      mosquito repellent potential and antihyperlipidaemic properties.In this study,
      the authors compare the composition of the volatile fractions of A. graveolens
      collected in natural populations in Portugal and Italy and evaluate their
      potential as antifungal agents.The composition of the volatile oils obtained by
      hydrodistillation and their antifungal activity are reported. The oils were
      analysed by gas chromatography-flame ionisation detector and gas chromatography
      mass spectrometry methods and their composition were compared with that of the
      volatile extracts isolated by supercritical CO2. A chemical variability in the
      extracts depending on the origin of the plants and on the extraction method was
      observed. The results showed the presence of sedanenolide, neocnidilide and
      neophytadiene as main components. The minimal inhibitory concentration (MIC) and
      the minimal lethal concentration were used to evaluate the antifungal activity of
      the oils against Candida albicans, Candida tropicalis, Candida krusei, Candida
      guilliermondii, Candida parapsilosis, Cryptococcus neoformans, Trichophyton
      rubrum, Trichophyton mentagrophytes, T. mentagrophytes var. interdigitale,
      Trichophyton verrucosum, Microsporum canis, Microsporum gypseum, Epidermophyton
      floccosum, Aspergillus niger, Aspergillus fumigatus and Aspergillus flavus. The
      oil from Italy rich in neophytadiene is the more active, with MIC values of 0.04
      0.64 uL mL(-1). Our results show that A. graveolens volatile extracts may be
      useful in the clinical treatment of fungal diseases.

PMID- 22974402
TI  - Special issue: multi-criteria approaches in computer-aided drug discovery.

PMID- 22974403
TI  - Naturalized Escherichia coli from New Zealand wetland and stream environments.
AB  - This research investigates the presence of a naturalized clade of Escherichia
      coli in wetland and stream biofilms. Escherichia coli is used as a faecal
      indicator in water quality monitoring programmes worldwide, with the assumption
      that this bacterium is exclusively a commensal of the vertebrate gut. However,
      recent findings indicate growth and multiplication of E. coli in water and soils.
      This study seeks to clarify the relationships between environmental and commensal
      E. coli strains retrieved from New Zealand streams by evaluating fundamental
      genetic differences using the multilocus sequence typing (MLST) method.
      Environmental and commensal strains showed a high diversity of MLST profiles.
      Genetic analyses of linkage disequilibrium, index of association and rates of
      synonymous and nonsynonymous substitutions were used to investigate sequence
      variability and nature of change. Phylogenetic trees based on the concatenated
      sequences of the seven MLST housekeeping genes displayed distinct clustering of
      environmental strains. Comparison of the New Zealand sequences with worldwide E.
      coli strains retrieved from the Shigatox MLST database online did not allow the
      identification of a clear environmental genotype. However, some New Zealand
      aquatic E. coli isolates showed close relationships with strains from human and
      bovine origins, suggesting that environmental isolates were originally derived
      from subpopulations of commensal E. coli from these sources.

PMID- 22974404
TI  - Who tended to continue smoking after cancer diagnosis: the national health and
      nutrition examination survey 1999-2008.
AB  - BACKGROUND: It has been estimated that there are approximately 12 million cancer
      survivors in the United States. Continued smoking after a cancer diagnosis is
      linked to adverse effects among cancer survivors on overall survival, treatment
      effectiveness, and quality of life. Little is known about who is more likely to
      quit smoking after his/her cancer diagnosis. The objective of this study is to
      evaluate factors associated with smoking cessation in cancer survivors, which to
      date has not been well studied. METHOD: The National Health and Nutrition
      Examination Survey (NHANES) 1999-2008 surveys were used in this study. A total of
      2,374 cancer survivors aged 20 and over with valid smoking status in the NHANES
      99-08 survey were included in this study. Among them, 566 cancer survivors who
      regularly smoked at the time of their cancer diagnosis were included in the
      analyses. RESULTS: Around 50.6% of cancer survivors smoked regularly prior to
      their cancer diagnosis and only 36.1% of them quit smoking after their cancer
      diagnosis. Racial disparity was observed in smoking cessation among cancer
      survivors. Hispanics (OR = 0.23, 95% CI = 0.10-0.57) were less likely to quit
      smoking than Whites after their cancer diagnosis. CONCLUSION: Two-thirds of
      cancer survivors continued smoking after cancer diagnosis. Our study observed
      that the high risk group of continued smokers among cancer survivors is made up
      of those who are female, younger, Hispanic, with longer smoking history,
      underweight or with normal weight and without smoking-related cancer. These
      findings suggest that smoking cessation for cancer survivors should target on the
      high risk subgroups.

PMID- 22974405
TI  - A protocol for a systematic review for perioperative pregabalin use.
AB  - BACKGROUND: Perioperative pain management has recently been revolutionized with
      the recognition of novel mechanisms and introduction of newer drugs. Many
      randomized trials have studied the use of the gabapentinoid anti-epileptic,
      pregabalin, in acute pain. Published systematic reviews suggest that using
      pregabalin for perioperative pain management may decrease analgesic requirements
      and pain scores, at the expense of troublesome side effects. A major limitation
      of the extant reviews is the lack of rigorous investigation of clinical
      characteristics that would maximize the benefit harms ratio in favor of surgical
      patients. We posit that effects of pregabalin for perioperative pain management
      vary by the type of surgical pain model and propose this systematic review
      protocol to update previous systematic reviews and investigate the heterogeneity
      in findings across subgroups of surgical pain models. METHODS/DESIGN: Using a
      peer-reviewed search strategy, we will search key databases for clinical trials
      on perioperative pregabalin use in adults. The electronic searches will be
      supplemented by scanning the reference lists of included studies. No limits of
      language, country or year will be imposed. Outcomes will include pain; use of co
      analgesia, particularly opioids; enhanced recovery; and drug-related harms. We
      will focus on the identification of surgical models and patient characteristics
      that have shown benefit and adverse effects from pregabalin.Two clinical experts
      will independently screen the studies for inclusion using eligibility criteria
      established a priori. Data extracted by the reviewers will then be verified.
      Publication bias will be assessed, as will risk of bias using the Cochrane Risk
      of Bias tool. Meta-analysis and meta-regression are planned if the studies are
      deemed statistically, methodologically and clinically homogenous. Evidence will
      be graded for its strength for a select number of outcomes. DISCUSSION: We will
      explore the findings of perioperative clinical trials studying the use of
      pregabalin for acute pain. We will comment on the implications of the findings
      and provide further direction for the appropriate use of pregabalin in acute
      pain. This protocol will attempt to bridge the growing gap between clinical
      experience and emerging evidence, and has the potential to aid future guideline
      development in the perioperative use of pregabalin. TRIAL REGISTRATION: PROSPERO
      registration number CRD42012002078.

PMID- 22974406
TI  - A surgical technique for excision of epidermal cysts.

PMID- 22974407
TI  - Insights into the mechanism of an S(N)2 reaction from the reaction force and the
      reaction electronic flux.
AB  - The mechanism of a simple S(N)2 reaction, viz; OH(-) + CH(3)F = CH(3)OH + F(-)
      has been studied within the framework of reaction force and reaction electronic
      flux. We have computationally investigated three different types of reaction
      mechanisms with two different types of transition states, leading to two
      different products. The electronic transfer contribution of the reaction
      electronic flux was found to play a crucial role in this reaction. Natural bond
      order analysis and dual descriptor provide additional support for elucidating the
      mechanism of this reaction.

PMID- 22974408
TI  - Transient solutions to groundwater mounding in bounded and unbounded aquifers.
AB  - In this study, the well-known Hantush solution procedure for groundwater mounding
      under infinitely long infiltration strips is extended to finite and semi-infinite
      aquifer cases. Initially, the solution for infinite aquifers is presented and
      compared to those available in literature and to the numerical results of
      MODFLOW. For the finite aquifer case, the method of images, which is commonly
      used in well hydraulics, is used to be able to represent the constant-head
      boundaries at both sides. It is shown that a finite number of images is enough to
      obtain the results and sustain the steady state. The effect of parameters on the
      growth of the mound and on the time required to reach the steady state is
      investigated. The semi-infinite aquifer case is emphasized because the growth of
      the mound is not symmetric. As the constant-head boundary limits the growth, the
      unbounded side grows continuously. For this reason, the groundwater divide shifts
      toward the unbounded side. An iterative solution procedure is proposed. To
      perform the necessary computations a code was written in Visual Basic of which
      the algorithm is presented. The proposed methodology has a wide range of
      applicability and this is demonstrated using two practical examples. The first
      one is mounding under a stormwater dispersion trench in an infinite aquifer and
      the other is infiltration from a flood control channel into a semi-infinite
      aquifer. Results fit very well with those of MODFLOW.

PMID- 22974409
TI  - Anti-Staphylococcus aureus action of three Caatinga fruits evaluated by electron
      microscopy.
AB  - This study evaluated the antibacterial activity of Anadenanthera colubrina,
      Libidibia ferrea and Pityrocarpa moniliformis fruit extracts against clinical
      strains of Staphylococcus aureus. The samples were active for all S. aureus
      strains (minimum inhibitory concentration: 0.38-3.13 mg mL-1), including the
      multiresistant strain. The morphological changes suggested the cell wall as the
      main action target. The treated-cells also lose their ability to form aggregates.
      The analysis suggests cell wall impairment, which causes the loss of viability
      and death. This study showed for the first time the morphologic alterations
      involved in the anti-S. aureus action of fruits of A. colubrina, L. ferrea and P.
      moniliformis. These findings indicated that these fruit extracts are sources of
      bioactive compounds that can be used as antibacterial agents.

PMID- 22974410
TI  - Long-term outcomes of salvage radical cystectomy for recurrent urothelial
      carcinoma of the bladder following partial cystectomy.
AB  - Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject?
      and What does the study add? Data on the oncological outcomes in patients
      undergoing salvage cystectomy for recurrent disease following bladder-sparing
      treatment is limited and mostly based on case reports. We present the clinical
      outcomes and prognostic factors in patients undergoing radical cystectomy for
      recurrent disease following partial cystectomy with long-term follow-up.
      OBJECTIVE: To report the clinical outcomes and prognostic factors in patients
      undergoing salvage radical cystectomy (sRC) for recurrent urothelial carcinoma
      (UC) of the bladder following partial cystectomy (PC). PATIENTS AND METHODS:
      Between 1971 and 2011, a total of 2290 patients underwent radical cystectomy for
      UC of the bladder, including 72 patients (3.1%) who underwent sRC following PC.
      Clinical and pathological data at the time of both PC and sRC were collected.
      Median follow-up time after sRC was 10.9 years. Overall survival and recurrence
      free survival were the primary outcomes of interest. Univariate and multivariate
      analyses were performed to identify prognostic factors after sRC. RESULTS: The
      median time from PC to sRC was 1.6 years. Median age at sRC was 64 years. Peri
      operative mortality was 2.8%. After sRC, 44 patients (61.2%) had pathologically
      organ-confined disease, 14 patients (19.4%) extravesical disease and 14 patients
      (19.4%) lymph node positive disease. Five-year recurrence-free survival and
      overall survival following sRC were 56% and 41%, respectively. On multivariate
      analysis, the presence of pathological tumor stage >=pT3a (hazard ratio 6.86, P <
      0.001) and the presence of lymph node metastases (hazard ratio 8.78, P < 0.001)
      were associated with increased risk of recurrence after sRC. CONCLUSIONS: sRC can
      provide prolonged survival following failure of PC. Prognosis, however, is highly
      dependent on pathological tumour stage and nodal status at sRC. Only 15% of
      patients with locally advanced recurrent disease were salvaged by sRC.

PMID- 22974411
TI  - The hydrogen games and other adventures in chemistry.
AB  - I seem to have started off on the wrong foot in life, but I am extremely
      fortunate that I soon found my footing in the company of physical chemists. I
      consider myself to be very lucky to be doing something that constantly brings me
      in contact with bright minds, stimulating conversations, and exciting
      experiments. My work has allowed me to learn astounding facts about the molecules
      and atoms that make up our surroundings and ourselves. For this article, I focus
      on one aspect of my research, understanding the fundamental principles of the
      simple reaction between a hydrogen atom and a hydrogen molecule. Although my
      group and others have been studying this seemingly simple reaction for well over
      30 years, it continues to provoke questions about the properties of matter.

PMID- 22974412
TI  - Effect of metformin glycinate on glycated hemoglobin A1C concentration and
      insulin sensitivity in drug-naive adult patients with type 2 diabetes mellitus.
AB  - AIM: This study evaluated the effect of metformin glycinate on glycated
      hemoglobin A1c (A1C) concentration and insulin sensitivity in drug-naive adult
      patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: A
      randomized, double-blind, placebo-controlled clinical trial was carried out in 20
      patients with drug-naive T2DM. Ten subjects received metformin glycinate (1,050.6
      mg) once daily during the first month and force-titrated twice daily during the
      second month. Ten additional patients received placebo as the control group.
      Before and after the intervention, metabolic profile including A1C and insulin
      sensitivity (euglycemic-hyperinsulinemic clamp technique) was estimated. RESULTS:
      A1C concentrations decreased significantly with metformin glycinate
      administration (8.0 +/- 0.7% vs. 7.1 +/- 0.9%, P = 0.008) before and after the
      intervention, respectively. There were significant differences in changes from
      baseline of A1C between groups (0.0 +/- 0.7% vs. -1.0 +/- 0.5% for placebo and
      metformin glycinate groups, respectively; P = 0.004). A reduction of >=1% in A1C
      levels was reached in 60.0% of patients with metformin glycinate administration
      (P = 0.02). Insulin sensitivity was not modified by the intervention.
      CONCLUSIONS: Administration of metformin glycinate during a 2-month period showed
      a greater decrease in A1C concentrations than placebo in a selected group of drug
      naive adult patients with T2DM.

PMID- 22974413
TI  - Peripheral stepwise degradation of a porphyrin J-aggregate.
AB  - For metalation of the acidic form of tetrakis(4-sulfonatophenyl)porphyrin
      (dianionic H(4)TPPS(4)) by Cu(II), the order of reagent mixing determines the
      rate and mechanism of CuTPPS(4) formation. When copper salts are added last, the
      kinetic profile is fit as a (pseudo)-first-order process. However, J-aggregates
      of the H(4)TPPS(4) porphyrin are rapidly formed at pH ~ 3 when Cu(II) salts are
      incorporated in solution prior to porphyrin addition. The subsequent porphyrin
      units metalation leads to the disassembling of these arrays via a pseudo-zero
      order kinetic profile, suggesting an attack of the metal ion at the rims of the
      nanostructure.

PMID- 22974414
TI  - HIV disclosure, sexual negotiation and male involvement in prevention-of-mother
      to-child-transmission in South Africa.
AB  - HIV-seroconversion during pregnancy is a serious concern throughout South Africa,
      where an estimated 35 to 40% of pregnant women have HIV/AIDS and drop-out is high
      at all stages of the prevention-of-mother-to-child-transmission (PMTCT) process.
      The likelihood of PMTCT success may be linked to partner support, yet male
      involvement in antenatal care remains low. This qualitative study examined the
      influence of pregnant couples' expectations, experiences and perceptions on
      sexual communication and male involvement in PMTCT. A total of 119 couples
      participated in a comprehensive intervention in 12 antenatal clinics throughout
      South Africa. Data were collected between December 2010 to June 2011 and analysed
      using a grounded theory approach. Findings point to the importance of sexual
      communication as a factor influencing PMTCT male involvement. Analysis of themes
      lends support to improving communication between couples, encouraging dialogue
      among men and increasing male involvement in PMTCT to bridge the gap between
      knowledge and sexual behaviour change.

PMID- 22974415
TI  - Neuroprotective effect of epigallocatechin-3-gallate against N-methyl-D-aspartate
      induced excitotoxicity in the adult rat retina.
AB  - PURPOSE: Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea,
      has been suggested to reduce glutamate excitotoxicity. We therefore investigated
      the potentially protective effects of EGCG against N-methyl-d-aspartate (NMDA)
      induced excitotoxicity in the retina. METHODS: Female Wistar rats (n = 171) were
      divided into a normal control group (n = 9); saline control group with
      intravitreal saline injections (n = 54); NMDA control group with an intravitreal
      NMDA injection and intraperitoneal saline injections (n = 54); and NMDA study
      group (n = 54) receiving an intravitreal NMDA injection plus intraperitoneal EGCG
      (25 mg/kg) injections. Starting at 2 days prior to the intravitreal NMDA
      injection, the intraperitoneal injections were performed daily for the whole
      study period. At 12 hr, 1, 2, 3 days, 1 and 2 weeks after the intravitreal NMDA
      injection, the animals were killed. We counted the neurons in the retinal
      ganglion cell layer (GCL) on histological sections, measured the thickness of Thy
      1 immunoreactivity and assessed the expression of Thy-1 mRNA by real-time
      polymerase chain reaction. RESULTS: At all time-points, GCL cell density,
      thickness of Thy-1 immunoreactivity and expression of Thy-1 mRNA were
      significantly (all p < 0.05) lower in the NMDA control group than in the NMDA
      study group, in which the parameters were significantly (all p < 0.05) lower than
      in the saline control group and the normal control group. In both groups with an
      intravitreal NMDA injection, GCL cell density, thickness of Thy-1
      immunoreactivity and expression of Thy-1 mRNA decreased significantly with
      increasing follow-up time. CONCLUSIONS: Intraperitoneal application of EGCG
      resulted in a significantly less marked NMDA-associated loss of retinal ganglion
      cells.

PMID- 22974416
TI  - Adult deaths and the future: a cause-specific analysis of adult deaths from a
      longitudinal study in rural Tanzania 2003-2007.
AB  - OBJECTIVES: To determine patterns and risk factors for cause-specific adult
      mortality in rural southern Tanzania. METHODS: The study was a longitudinal open
      cohort and focused on adults aged 15-59 years between 2003 and 2007. Causes of
      deaths were ascertained by verbal autopsy (VA). Cox proportion hazards regression
      model was used to determine factors associated with cause-specific mortality over
      the 5-year period. RESULTS:   Thousand three hundred and fifty-two of 65 548
      adults died, representing a crude adult mortality rate (AMR) of 7.3 per 1000
      person years of observation (PYO). VA was performed for 1132 (84%) deaths.
      HIV/AIDS [231 (20.4%)] was the leading cause of death followed by malaria [150
      (13.2%)]. AMR for communicable disease (CD) causes was 2.49 per 1000 PYO, 1.21
      per 1000 PYO for non-communicable diseases (NCD) and 0.53 per 1000 PYO for
      accidents/injury causes. NCD deaths increased from 16% in 2003 to 24% in 2007.
      High level of education was associated with a reduction in the risk of dying from
      NCDs. Those with primary education (HR = 0.67, 95% CI: 0.49, 0.92) and with
      education beyond primary school (HR = 0.11, 95% CI: 0.02, 0.40) had lower
      mortality than those who had no formal education. Compared with local residents,
      in-migrants were 1.7 (95% CI: 1.37, 2.11) times more likely to die from
      communicable disease causes. CONCLUSION: NCDs are increasing as a result of
      demographic and epidemiological transitions taking place in most African
      countries including Tanzania and require attention to prevent increased triple
      disease burden of CD, NCD and accident/injuries.

PMID- 22974417
TI  - Experiences of leadership in health care in sub-Saharan Africa.
AB  - BACKGROUND: Leadership is widely regarded as central to effective health-care
      systems, and resources are increasingly devoted to the cultivation of strong
      health-care leadership. Nevertheless, the literature regarding leadership
      capacity building has been developed primarily in the context of high-income
      settings. Less research has been done on leadership in low-income settings,
      including sub-Saharan Africa, particularly in health care, with attention to
      historical, political and sociocultural context. We sought to characterize the
      experiences of individuals in key health-care leadership roles in sub-Saharan
      Africa. METHODS: We conducted a qualitative study using in-person interviews with
      individuals (n = 17) in health-care leadership roles in four countries in sub
      Saharan Africa: the Federal Democratic Republic of Ethiopia, the Republic of
      Ghana, the Republic of Liberia and the Republic of Rwanda. Individuals were
      identified by their country's minister of health as key leaders in the health
      sector and were nominated to serve as delegates to a global health leadership
      conference in June 2010, at Yale University in the United States. Interviews were
      audio recorded and professionally transcribed. Data analysis was performed by a
      five-person multidisciplinary team using the constant comparative method,
      facilitated by ATLAS.ti 5.0 software. RESULTS: Five key themes emerged as
      important to participants in their leadership roles: having an aspirational,
      value-based vision for improving the future health of the country, being self
      aware and having the ability to identify and use complementary skills of others,
      tending to relationships, using data in decision making, and sustaining a
      commitment to learning. CONCLUSIONS: Current models of leadership capacity
      building address the need for core technical and management competencies. While
      these competencies are important, skills relevant to managing relationships are
      also critical in the sub-Saharan African context. Developing such skills may
      require more time and a deeper level of engagement and collaboration than is
      typically invested in efforts to strengthen health systems.

PMID- 22974418
TI  - In vivo, cardiac-specific knockdown of a target protein, malic enzyme-1, in rat
      via adenoviral delivery of DNA for non-native miRNA.
AB  - This study examines the feasibility of using the adenoviral delivery of DNA for a
      non-native microRNA to suppress expression of a target protein (cytosolic NADP(+)
      dependent malic-enzyme 1, ME1) in whole heart in vivo, via an isolated-heart
      coronary perfusion approach. Complementary DNA constructs for ME1 microRNA were
      inserted into adenoviral vectors. Viral gene transfer to neonatal rat
      cardiomyocytes yielded 65% suppression of ME1 protein. This viral package was
      delivered to rat hearts in vivo (Adv.miR_ME1, 10(13) vp/ml PBS) via coronary
      perfusion, using a cardiac-specific isolation technique. ME1 mRNA was reduced by
      73% at 2-6 days post-surgery in heart receiving the Adv.miR_ME1. Importantly, ME1
      protein was reduced by 66% (p < 0.0002) at 5-6 days relative to sham-operated
      control hearts. Non-target protein expression for GAPDH, calsequestrin, and
      mitochondrial malic enzyme, ME3, were all unchanged. The non-target isoform, ME2,
      was unchanged at 2-5 days and reduced at day 6. This new approach demonstrates
      for the first time significant and acute silencing of target RNA translation and
      protein content in whole heart, in vivo, via non-native microRNA expression.

PMID- 22974419
TI  - Growth responses following a single intra-muscular hGH plasmid administration
      compared to daily injections of hGH in dwarf mice.
AB  - In previous work, sustained levels of circulating human growth hormone (hGH) and
      a highly significant weight increase were observed after electrotransfer of naked
      plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid).
      In the present study, the efficacy of this in vivo gene therapy strategy is
      compared to daily injections (5 MUg/twice a day) of recombinant hGH (r-hGH)
      protein, as assessed on the basis of several growth parameters. The slopes of the
      two growth curves were found to be similar (P > 0.05): 0.095 g/mouse/d for
      protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases
      averaged 35.5% (P < 0.001) and 23.1% (P < 0.01) for protein and DNA
      administration, respectively, a difference possibly related to the
      electroporation methodology. The nose-to-tail linear growth increases were 15%
      and 9.6% for the protein and DNA treatments, respectively, but mouse insulin-like
      growth factor I (mIGF-I) showed a greater increase over the control with DNA (5-
      to 7-fold) than with protein (3- to 4-fold) administration. The weight increases
      of several organs and tissues (kidneys, spleen, liver, heart, quadriceps and
      gastrocnemius muscles) were 1.3- to 4.6-fold greater for protein than for DNA
      administration, which gave a generally more proportional growth. Glucose levels
      were apparently unaffected, suggesting the absence of effects on glucose
      tolerance. A gene transfer strategy based on a single hGH-DNA administration thus
      appears to be comparable to repeated hormone injections for promoting growth and
      may represent a feasible alternative for the treatment of growth hormone
      deficiency.

PMID- 22974420
TI  - Induction of apoptosis and sensitization of head and neck squamous carcinoma
      cells to cisplatin by targeting survivin gene expression.
AB  - Survivin is known to be highly-expressed in various carcinomas; and is associated
      with their biologically aggressive characteristics and drug resistance. We have
      previously reported survivin as an important anti-apototic protein involved in
      head and neck squamous cell carcinoma (HNSCC) tumorigenesis and providing
      resistance to conventional cancer therapies. The purpose of present study was to
      investigate the potential of survivin as a therapeutic target in HNSCC. This
      study was designed to explore the effect(s) of survivin-siRNA therapy on the
      apoptosis in HNSCC cells, and its influence on cisplatin-sensitivity. Lentivirus
      vector was developed to deliver survivin specific siRNA into cancer cells. The
      data indicates that silencing of survivin-mediated by Lentivirus-siRNA therapy
      effectively suppressed cancer cell proliferation and induced caspase-dependent
      apoptosis in HNSCC cells. The study also shows that the response of HNSCC cells
      to cisplatin drug treatment at clinically relevant level was limited. We observed
      survivin to be a key factor involved in this cisplatin-resistance mechanism, and
      down-regulation of survivin significantly increased sensitivity of cancer cells
      to cisplatin-mediated apoptosis. Thus, this combination therapy acts as a
      multimodality regimen with significant potential to improve clinical outcomes in
      head and neck cancers.

PMID- 22974421
TI  - Equipping CAR-modified T cells with a brake to prevent chronic adverse effects.
AB  - Genetical modification of T lymphocytes by chimeric antigen receptor (CAR), which
      has the affinity to tumor associated antigen (TAA), can redirect the normal T
      lymphocytes with tumor specificity. Through optimization of the CAR construct
      from first generation to third generation, the properties of these CAR-modified T
      lymphocytes, including, cytokines release, proliferative capacity, in vivo
      survival time, have been remarkably improved. These improvements accelerate the
      clinical applications of the CAR-modified T lymphocytes. Due to CD19, and CD20
      specificity, CAR-modified T lymphocytes have been clinically used to treat
      leukemia. Notably, T lymphocytes genetically engineered by Carl June group with
      CAR targeting to CD19 have expanded more than 1,000 folds by clearing all CD19
      positive leukemia cells, even the normal B cells, which infiltrated in bone
      marrow, and survived for more than 6 months. This encouraging report demonstrates
      the overwhelming tumor-lytic ability of the CAR-modified T lymphocytes; it also
      raises the concern about the chronic toxicity. Here, we emphasize the safety
      concern when using the CAR-modified T lymphocytes. We also summarize strategies
      exploited to clear the genetically engineered T lymphocytes under an urgent
      condition, which increases the safety and optimizes the applications of the CAR
      modified T lymphocytes.

PMID- 22974422
TI  - Microbial ecology of the rumen evaluated by 454 GS FLX pyrosequencing is affected
      by starch and oil supplementation of diets.
AB  - To provide a comprehensive examination of the bacterial diversity in the rumen
      content of cows fed different diets, high-throughput 16S rRNA gene-based
      pyrosequencing was used. Four rumen fistulated nonlactating Holstein cows
      received 12 kg of dry matter per day of four diets based on maize silage during
      four periods: the low-starch diet (22% starch, 3% fat); the high-starch diet,
      supplemented with wheat plus barley (35% starch, 3% fat); the low-starch plus oil
      diet, supplemented with 5% of sunflower oil (20% starch, 7.6% fat) and the high
      starch plus oil diet (33% starch, 7.3% fat). Samples were taken after 12 days of
      adaptation, 5 h postfeeding. Whatever the diet, bacterial community of sieved
      rumen contents was dominated by Firmicutes and Bacteroidetes. Lachnospiraceae,
      Ruminococcaceae, Prevotellaceae, and Rikenellaceae families were highly present
      and were clearly affected by cow diet. The highest abundance of Prevotellaceae
      and the lowest abundance of Ruminococcaceae and Rikenellaceae were found with the
      high-starch plus oil diet. Dietary starch increased the relative abundance of
      only three genera: Barnesiella, Oribacterium and Olsenella, but decreased the
      relative abundances of several genera, with very significant effects for
      Rikenellaceae_RC9 and Butyrivibrio-Pseudobutyrivibrio. Oil alone had a limited
      effect, but interestingly, starch plus oil addition differently affected the
      bacterial populations compared to starch addition without oil.

PMID- 22974423
TI  - Delay of iris flower senescence by cytokinins and jasmonates.
AB  - It is not known whether tepal senescence in Iris flowers is regulated by
      hormones. We applied hormones and hormone inhibitors to cut flowers and isolated
      tepals of Iris * hollandica cv. Blue Magic. Treatments with ethylene or ethylene
      antagonists indicated lack of ethylene involvement. Auxins or auxin inhibitors
      also did not change the time to senescence. Abscisic acid (ABA) hastened
      senescence, but an inhibitor of ABA synthesis (norflurazon) had no effect.
      Gibberellic acid (GA3 ) slightly delayed senescence in some experiments, but in
      other experiments it was without effect, and gibberellin inhibitors [ancymidol or
      4-hydroxy-5-isopropyl-2-methylphenyltrimethyl ammonium chloride-1-piperidine
      carboxylate (AMO-1618)] were ineffective as well. Salicylic acid (SA) also had no
      effect. Ethylene, auxins, GA3 and SA affected flower opening, therefore did reach
      the flower cells. Jasmonates delayed senescence by about 2.0 days. Similarly,
      cytokinins delayed senescence by about 1.5-2.0 days. Antagonists of the
      phosphatidylinositol signal transduction pathway (lithium), calcium channels
      (niguldipine and verapamil), calmodulin action [fluphenazine, trifluoroperazine,
      phenoxybenzamide and N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide
      hydrochloride (W-7)] or protein kinase activity [1-(5-isoquinolinesulfonyl)-2
      methylpiperazine hydrochloride (H-7), N-[2-(methylamino)ethyl]-5
      isoquinolinesulfonamide hydrochloride (H-8) and N-(2-aminoethyl)-5
      isoquinolinesulfonamide dihydrochloride (H-9)] had no effect on senescence,
      indicating no role of a few common signal transduction pathways relating to
      hormone effects on senescence. The results indicate that tepal senescence in Iris
      cv. Blue Magic is not regulated by endogenous ethylene, auxin, gibberellins or
      SA. A role of ABA can at present not be excluded. The data suggest the hypothesis
      that cytokinins and jasmonates are among the natural regulators.

PMID- 22974424
TI  - The production of beta-glucosidases by Fusarium proliferatum NBRC109045 isolated
      from Vietnamese forest.
AB  - Fusarium proliferatum NBRC109045 is a filamentous fungus isolated from
      Vietnamese forest due to high production of beta-glucosidases. Production of the
      enzyme was studied on varied carbon source based mediums. The highest activity
      was obtained in medium containing 1% corn stover + 1% wheat bran (3.31 +/- 0.14
      U/ml). It is interesting to note that glucose (0.69 +/- 0.02 U/ml) gave higher
      activity and just followed by cellobiose among the di- and mono-saccharides,
      which is generally regarded as a universal repressor of hydrolases. We improved
      the zymogram method to prove that in response to various carbon sources, F.
      proliferatum could express various beta-glucosidases. One of the beta
      glucosidases produced by F. proliferatum growing in corn stover + wheat bran
      based medium was partially purified and proved to have high catalytic ability.

PMID- 22974425
TI  - Better survival of random pattern skin flaps through the use of epigallocatechin
      gallate.
AB  - BACKGROUND: Surgical skin flaps are useful, but flap necrosis is a common
      problem. Epigallocatechin gallate (EGCG), the major polyphenol of green tea, has
      been investigated as a neovascularization agent to counteract necrosis.
      OBJECTIVES: To evaluate the effect of EGCG on random pattern skin flap survival.
      MATERIALS AND METHODS: The rat dorsal skin flap model was employed. One hundred
      rats were divided into five groups of equal size. Experimental Group A received
      local injection of EGCG to the flap, experimental Group B received topical
      application of EGCG, control Group C received local injection of saline, control
      Group D received topical application of an acetone-olive oil mixture, and control
      Group E received no treatment. The surviving area of the flap, regional blood
      perfusion, capillary density, and vascular endothelial growth factor (VEGF)
      expression were evaluated. RESULTS: We observed a larger area of skin flap
      survival in Groups A and B than in the control groups. Doppler measurement showed
      greater perfusion in Groups A and B, and the capillary density and VEGF
      expression were significantly higher in the experimental animals. CONCLUSION: The
      EGCG treatment enhanced neovascularization and regional perfusion and, as a
      result, improved skin flap survival.

PMID- 22974426
TI  - Assessing the relative bioavailability of DOC in regional groundwater systems.
AB  - It has been hypothesized that the degree to which a hyperbolic relationship
      exists between concentrations of dissolved organic carbon (DOC) and dissolved
      oxygen (DO) in groundwater may indicate the relative bioavailability of DOC. This
      hypothesis was examined for 73 different regional aquifers of the United States
      using 7745 analyses of groundwater compiled by the National Water Assessment
      (NAWQA) program of the U.S. Geological Survey. The relative reaction quotient
      (RRQ), a measure of the curvature of DOC concentrations plotted versus DO
      concentrations and regressed to a decaying hyperbolic equation, was used to
      assess the relative bioavailability of DOC. For the basalt aquifer of Oahu,
      Hawaii, RRQ values were low (0.0013 mM(-2)), reflecting a nearly random
      relationship between DOC and DO concentrations. In contrast, on the island of
      Maui, treated sewage effluent injected into a portion of the basalt aquifer
      resulted in pronounced hyperbolic DOC-DO behavior and a higher RRQ (142 mM(-2)).
      RRQ values for the 73 aquifers correlated positively with mean concentrations of
      ammonia, dissolved iron, and manganese, and correlated negatively with mean pH.
      This indicates that greater RRQ values are associated with greater concentrations
      of the final products of microbial reduction reactions. RRQ values and DOC
      concentrations were negatively correlated with the thickness of the unsaturated
      zone (UNST) and depth to the top of the screened interval. Finally, RRQ values
      were positively correlated with mean annual precipitation (MAP), and the highest
      observed RRQ values were associated with aquifers receiving MAP rates ranging
      between 900 and 1300 mm/year. These results are uniformly consistent with the
      hypothesis that the hyperbolic behavior of DOC-DO plots, as quantified by the RRQ
      metric, can be an indicator of relative DOC bioavailability in groundwater
      systems.

PMID- 22974427
TI  - Expression of Bak and Bak/Mcl-1 ratio can predict photodynamic therapy outcome
      for oral verrucous hyperplasia and leukoplakia.
AB  - BACKGROUND: Our previous studies showed that topical 5-aminolevulinic acid
      mediated photodynamic therapy (ALA-PDT) is very effective for oral verrucous
      hyperplasia (OVH) and relatively less effective for oral leukoplakia (OL)
      lesions. Nevertheless, there has been no report on the association of the
      expression of apoptosis-related proteins in OVH and OL biopsy tissues prior to
      PDT with PDT treatment outcomes. METHODS: This study used immunohistochemistry to
      evaluate whether the expression of Bak, Mcl-1, caspase-3, caspase-8, caspase-9,
      p53, p21, or PCNA protein in biopsy specimens of OVH and OL lesions could be used
      to predict the clinical outcomes of 18 OVH and 40 OL lesions treated with topical
      ALA-PDT. The marker labeling score (LS) was defined as labeling index (positive
      cells/total cells) multiplied by staining intensity. The lesions after ALA-PDT
      treatment were divided into complete response (CR) group and partial or no
      response (PR/NR) group. RESULTS: The mean Bak LS and the mean Bak/Mcl-1 LS ratio
      were significantly higher in the CR group than in the PR/NR group. However, there
      was no significant difference in the Mcl-1, caspase-3, caspase-8, caspase-9, p53,
      p21, or PCNA protein LS between the CR and PR/NR groups. CONCLUSION: We conclude
      that the Bak LS or Bak/Mcl-1 LS ratio may be a useful biomarker to predict the
      clinical outcomes of OVH and OL lesions treated with topical ALA-PDT. Pre-PDT
      epithelial cell levels of Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, and
      PCNA may not have a significant influence on the clinical outcome of OVH and OL
      lesions treated with topical ALA-PDT.

PMID- 22974428
TI  - Minimal percentage of dose received by 90% of the urethra (%UD90) is the most
      significant predictor of PSA bounce in patients who underwent low-dose-rate
      brachytherapy (LDR-brachytherapy) for prostate cancer.
AB  - BACKGROUND: To clarify the significant clinicopathological and postdosimetric
      parameters to predict PSA bounce in patients who underwent low-dose-rate
      brachytherapy (LDR-brachytherapy) for prostate cancer. METHODS: We studied 200
      consecutive patients who received LDR-brachytherapy between July 2004 and
      November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant
      androgen deprivation therapy. One hundred and forty-two patients were treated
      with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in
      combination with external beam radiation therapy. The cut-off value of PSA bounce
      was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were
      investigated. Clinicopathological and postdosimetric parameters were evaluated to
      elucidate independent factors to predict PSA bounce in hormone-naive patients who
      underwent LDR-brachytherapy alone. RESULTS: Fifty patients (25%) showed PSA
      bounce and 10 patients (5%) showed PSA failure. The median time, height, and
      duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively.
      In 103 hormone-naive patients treated with LDR-brachytherapy alone, and
      univariate Cox proportional regression hazard model indicated that age and
      minimal percentage of the dose received by 30% and 90% of the urethra were
      independent predictors of PSA bounce. With a multivariate Cox proportional
      regression hazard model, minimal percentage of the dose received by 90% of the
      urethra was the most significant parameter of PSA bounce. CONCLUSIONS: Minimal
      percentage of the dose received by 90% of the urethra was the most significant
      predictor of PSA bounce in hormone-naive patients treated with LDR-brachytherapy
      alone.

PMID- 22974429
TI  - Fabrication of copper nanoparticles: advances in synthesis, morphology control,
      and chemical stability.
AB  - Metal nanoparticles have attracted great interest particularly because of the
      size dependence of physical and chemical properties and its enormous
      technological potential. Although most pioneering advancements refers to gold and
      silver, more recently there is growing interest in nanoparticles of copper,
      mostly due to its relatively low cost, which could allow the use of these small
      metal objects in large-scale nanotechnology applications, for example,
      antiseptics materials and metallic inks. However, the manufacture of copper
      nanoparticles stable in air with controlled size and shape has been a major
      challenge because of the relatively high reactivity of this element. Great
      efforts in getting the basic knowledge and synthesis know-how has gone into
      finding better ways to produce particles protected against oxidation and
      selfaggregation under normal conditions. In this review article, we briefly
      discuss a number of selected papers and recent patents on procedures and other
      issues related to the fabrication of copper nanoparticles. 

PMID- 22974430
TI  - Recent developments and patents on biological sensing using nanoparticles in
      microfluidic systems.
AB  - Microfluidic systems provide a total solution of biological and chemical analysis
      from the sample application to the display of the analysis results. A lot of
      developments on the point-of-care diagnostic applications have been reported and
      the commercial possibility is shown. To achieve sensitive and specific biological
      sensing, nanoparticles may provide a promising tool because they have similar
      length scale with the biomolecules. The nano-sensing technology suggests a
      molecular level detection of the biomolecules to pursue higher performance. In
      this review, recent developments and patents on the biological sensing using
      nanoparticles in microfluidic systems are discussed. An updated, systematic and
      rapid reference in the field of nano-biological sensing is provided.

PMID- 22974431
TI  - A forgotten founding father of the Pill: Ferdinand Peeters, MD.
AB  - Ferdinand Peeters, a practising gynaecologist from Turnhout, near Antwerp
      (Belgium), had a pivotal role in the development of a practical and viable
      modality of oral contraception, striking the balance between efficacy and an
      acceptably low incidence and severity of side effects. While, with regard to the
      origin of oral contraception, names like those of Pincus, Rock, and Djerassi come
      immediately to the fore, the work of Peeters has to a large extent faded from
      public memory. Still, it was Peeters who proposed to Schering AG in Berlin that a
      combination of 4 mg norethisterone acetate and 0.05 mg ethinylestradiol be used
      for ovulation suppression. He convinced the scientific staff of Schering of the
      potential benefits of what, after clinical trials, would finally emerge as
      Anovlar.

PMID- 22974432
TI  - Social and ethical determinants of sexuality: 4. Sexuality and families.
AB  - OBJECTIVES: To investigate the evolving relationship between sexuality and family
      formation. New family units exist today whose impact on society needs to be
      explored. METHODS: For each main area researched (anthropology, biology,
      sociology, sexology, ethics) we identified articles dealing with family
      formation, sexuality and reproduction using PubMed, ScienceDirect, Google,
      religious websites and texts. RESULTS: The three monotheistic religions and the
      cultures derived from these have considered sexuality as focused on reproduction.
      Presently, sexuality has acquired new dimensions, independent from reproduction,
      as contraception and IVF have separated procreation and sexuality. Thus, the very
      concept of family has been expanded and so-called 'unusual families' have proved
      not to be a danger per se for children born and raised within them. CONCLUSIONS:
      Human sexuality has moved away from having a purely reproductive function, but
      remains a powerful bond keeping families together, irrespective of the gender
      identity and the biological links of their members. Even among traditional
      societies, different types of families exist and the situation has become more
      complex as technical developments have made parenthood possible for people who in
      the past were excluded from it.

PMID- 22974433
TI  - Office hysteroscopic findings in patients with two, three, and four or more,
      consecutive miscarriages.
AB  - OBJECTIVES: To assess hysteroscopic findings in patients with two, three, and
      four or more, consecutive miscarriages, and to compare the prevalence of uterine
      abnormalities between women with different numbers of such miscarriages. METHODS:
      Two hundred and sixty-five women with two or more consecutive miscarriages were
      enrolled in the study. Patients were divided into three groups according to the
      number of their miscarriages: Group 1 (two miscarriages, n = 151), Group 2 (three
      miscariages, n = 69), and Group 3 (four or more miscarriages, n = 45). All
      participants underwent a diagnostic hysteroscopy. Congenital (arcuate uterus,
      septate uterus, unicornuate uterus) and acquired uterine abnormalities
      (intrauterine adhesions, polyp and submucous myoma) were recorded. The
      hysteroscopic results were compared between the groups. RESULTS: No anomalies
      were detected in 152 patients (57%), whereas 43 (16%) had a septate uterus, 30
      (11%) an arcuate uterus, three (1%) a unicornuate uterus, 18 (7%) intrauterine
      adhesions, 17 (6 %) endometrial polyps, and two (1%) a submucous myoma. No
      significant differences were found between the groups with regard to either
      congenital or acquired uterine abnormalities. CONCLUSIONS: Patients with two,
      three, and four or more consecutive miscarriages have a similar prevalence of
      uterine anatomical abnormalities. Diagnostic hysteroscopy should be carried out
      after two such miscarriages.

PMID- 22974434
TI  - Prevalence of visual problems in a rural population of Kenya.

PMID- 22974436
TI  - Prostate cancer: germline prediction for a commonly variable malignancy.
AB  - What's known on the subject? and What does the study add? Prostate cancer is a
      heterogeneous disease and biomarkers to predict its incidence and subsequent
      clinical behaviour are needed to tailor screening, prevention and therapeutic
      strategies. Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect
      prostate cancer incidence and/or clinical behaviour. Genome wide association
      studies (GWAS) have identified more common genetic variations that explain an
      estimated 20% of familial prostate cancer risk. In this review, we focus on the
      potential of germline genetic variation to provide biomarkers for prostate cancer
      screening, prevention and management. We discuss how germline genetics may have a
      role in treatment selection if reliable pharmacogenetic predictors of efficacy
      and toxicity can be identified. We have outlined possible mechanisms for
      including germline investigation in future prostate cancer clinical trials.
      OBJECTIVES: * Prostate cancer is a heterogeneous disease and biomarkers to
      predict its incidence and subsequent clinical behaviour are needed to tailor
      screening, prevention and therapeutic strategies. * In this review we focus on
      the potential of germline genetic variation to provide these biomarkers. METHODS:
      * We review the published literature on germline genetics in prostate cancer and
      examine the possibility of including germline genetic biomarkers in future
      prostate cancer clinical trials. RESULTS: * Rare mutations in genes such as
      BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical
      behaviour. * Genome-wide association studies (GWAS) have identified more common
      genetic variations that explain an estimated 20% of familial prostate cancer
      risk. * Germline genetics may have a role in treatment selection, if reliable
      pharmacogenetic predictors of efficacy and toxicity can be identified.
      CONCLUSION: * This rapidly emerging area of prostate cancer research may provide
      answers to current clinical conundrums in the prostate cancer treatment paradigm.
      We have outlined possible mechanisms for including germline investigation in
      future prostate cancer clinical trial design.

PMID- 22974435
TI  - The effectiveness of a self-reporting bedside pain assessment tool for oncology
      inpatients.
AB  - BACKGROUND: Pain is common during cancer treatment, and patient self-reporting of
      pain is an essential first step for ideal cancer pain management. However, many
      studies on cancer pain management report that, because pain may be
      underestimated, it is often inadequately managed. OBJECTIVE: The aim of this
      study was to evaluate the effectiveness of bedside self-assessment of pain
      intensity for inpatients using a self-reporting pain board. METHODS: Fifty
      consecutive inpatients admitted to the Oncology Department of Chungbuk National
      University Hospital were included in this observational prospective study from
      February 2011 to December 2011. The medical staff performed pain assessments by
      asking patients questions and using verbal rated scales (VRS) over 3 consecutive
      days. Then, for 3 additional days, patients used a self-reporting pain board
      attached to the bed, which had movable indicators representing 0-10 on a numeric
      rating scale (NRS) and the frequency of breakthrough pain. RESULTS: Patient
      reliability over the medical staff's pain assessment increased from 74% to 96%
      after applying the self-reporting pain board (p=0.004). The gap (mean+/-standard
      deviation [SD]) between the NRS reported by patients and the NRS recorded on the
      medical records decreased from 3.16+/-2.08 to 1.00+/-1.02 (p<0.001), and the
      level of patient satisfaction with pain management increased from 54% to 82%
      (p=0.002). CONCLUSION: This study suggests that the self-reporting bedside pain
      assessment tool provides a reliable and effective means of assessing pain in
      oncology inpatients.

PMID- 22974437
TI  - Kinetic inertness of the Mn2+ complexes formed with AAZTA and some open-chain
      EDTA derivatives.
AB  - The results of systematic equilibrium, kinetic, and relaxometric investigations
      carried out on the Mn(2+) complexes of open-chain and AAZTA ligands indicate that
      the [Mn(CDTA)](2-) complex has satisfactorily high kinetic inertness (t(1/2) = 12
      h at pH = 7.4), which, in turn, may allow its use as a contrast agent in the
      field of magnetic resonance imaging (as a replacement for Gd(3+)-based agents).

PMID- 22974438
TI  - Regulation of insulin secretion in human pancreatic islets.
AB  - Pancreatic beta cells secrete insulin, the body's only hormone capable of
      lowering plasma glucose levels. Impaired or insufficient insulin secretion
      results in diabetes mellitus. The beta cell is electrically excitable; in
      response to an elevation of glucose, it depolarizes and starts generating action
      potentials. The electrophysiology of mouse beta cells and the cell's role in
      insulin secretion have been extensively investigated. More recently, similar
      studies have been performed on human beta cells. These studies have revealed
      numerous and important differences between human and rodent beta cells. Here we
      discuss the properties of human pancreatic beta cells: their glucose sensing, the
      ion channel complement underlying glucose-induced electrical activity that
      culminates in exocytotic release of insulin, the cellular control of exocytosis,
      and the modulation of insulin secretion by circulating hormones and locally
      released neurotransmitters. Finally, we consider the pathophysiology of insulin
      secretion and the interactions between genetics and environmental factors that
      may explain the current diabetes epidemic.

PMID- 22974440
TI  - Indicators of quality use of medicines in South-East Asian countries: a
      systematic review.
AB  - OBJECTIVES: To identify indicators of quality use of medicines used in South-East
      Asian region. METHODS: A systematic review was conducted searching MEDLINE,
      Embase and The International Network for Rational Use of Drugs (INRUD) and The
      World Health Organization (WHO) website. Original studies or reports carried out
      in the South-East Asian region, explicitly using indicators to measure quality
      use of medicines, and published between January 2000 and July 2011 were included.
      RESULTS: A total of 17 studies conducted in 7 of 11 countries in South-East Asia
      were included. WHO indicators focusing on general medication use in health
      facilities were most widely used (10 studies). Twelve studies used non-WHO
      indicators for measuring quality use of medicines in clinical areas (geriatrics
      and obstetrics) or specific diseases, such as diarrhoea and pneumonia. In five
      studies, WHO indicators were used along with non-WHO indicators. There was little
      information available about validity, reliability and feasibility of the non-WHO
      indicators. The majority of indicators measured process rather than structure or
      outcome. There were very few indicators addressing non-communicable diseases.
      CONCLUSIONS: A limited number of studies have been published explicitly using
      indicators of quality use of medicines across South-East Asia. Importantly,
      existing indicators need to be complemented with valid, reliable and feasible
      indicators related to non-communicable diseases, particularly those with a high
      financial burden to meet the current medical challenges in the region.

PMID- 22974439
TI  - Functional insights from glutamate receptor ion channel structures.
AB  - X-ray crystal structures for the soluble amino-terminal and ligand-binding
      domains of glutamate receptor ion channels, combined with a 3.6-A-resolution
      structure of the full-length AMPA receptor GluA2 homotetramer, provide unique
      insights into the mechanisms of the assembly and function of glutamate receptor
      ion channels. Increasingly sophisticated biochemical, computational, and
      electrophysiological experiments are beginning to reveal the mechanism of action
      of partial agonists and suggest new models for the mechanism of action of
      allosteric modulators. Newly identified NMDA receptor ligands acting at novel
      sites offer hope for the development of subtype-selective modulators. The many
      unresolved issues include the role of the amino-terminal domain in AMPA receptor
      signaling and the mechanisms by which auxiliary proteins regulate receptor
      activity. The structural basis for ion permeation and ion channel block also
      remain areas of uncertainty, and despite substantial progress, molecular dynamics
      simulations have yet to reveal how glutamate binding opens the ion channel pore.

PMID- 22974442
TI  - Neurodynamics, tonality, and the auditory brainstem response.
AB  - Tonal relationships are foundational in music, providing the basis upon which
      musical structures, such as melodies, are constructed and perceived. A recent
      dynamic theory of musical tonality predicts that networks of auditory neurons
      resonate nonlinearly to musical stimuli. Nonlinear resonance leads to stability
      and attraction relationships among neural frequencies, and these neural dynamics
      give rise to the perception of relationships among tones that we collectively
      refer to as tonal cognition. Because this model describes the dynamics of neural
      populations, it makes specific predictions about human auditory neurophysiology.
      Here, we show how predictions about the auditory brainstem response (ABR) are
      derived from the model. To illustrate, we derive a prediction about population
      responses to musical intervals that has been observed in the human brainstem. Our
      modeled ABR shows qualitative agreement with important features of the human ABR.
      This provides a source of evidence that fundamental principles of auditory
      neurodynamics might underlie the perception of tonal relationships, and forces
      reevaluation of the role of learning and enculturation in tonal cognition.

PMID- 22974441
TI  - SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated
      signaling networks reveal an extensive potential interactome.
AB  - Specific peptide ligand recognition by modular interaction domains is essential
      for the fidelity of information flow through the signal transduction networks
      that control cell behavior in response to extrinsic and intrinsic stimuli. Src
      homology 2 (SH2) domains recognize distinct phosphotyrosine peptide motifs, but
      the specific sites that are phosphorylated and the complement of available SH2
      domains varies considerably in individual cell types. Such differences are the
      basis for a wide range of available protein interaction microstates from which
      signaling can evolve in highly divergent ways. This underlying complexity
      suggests the need to broadly map the signaling potential of systems as a
      prerequisite for understanding signaling in specific cell types as well as
      various pathologies that involve signal transduction such as cancer,
      developmental defects and metabolic disorders. This report describes interactions
      between SH2 domains and potential binding partners that comprise initial
      signaling downstream of activated fibroblast growth factor (FGF), insulin (Ins),
      and insulin-like growth factor-1 (IGF-1) receptors. A panel of 50 SH2 domains
      screened against a set of 192 phosphotyrosine peptides defines an extensive
      potential interactome while demonstrating the selectivity of individual SH2
      domains. The interactions described confirm virtually all previously reported
      associations while describing a large set of potential novel interactions that
      imply additional complexity in the signaling networks initiated from activated
      receptors. This study of pTyr ligand binding by SH2 domains provides valuable
      insight into the selectivity that underpins complex signaling networks that are
      assembled using modular protein interaction domains.

PMID- 22974443
TI  - Effect of eplerenone on parathyroid hormone levels in patients with primary
      hyperparathyroidism: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Increasing evidence suggests the bidirectional interplay between
      parathyroid hormone and aldosterone as an important mechanism behind the
      increased risk of cardiovascular damage and bone disease observed in primary
      hyperparathyroidism. Our primary object is to assess the efficacy of the
      mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone
      secretion in patients with parathyroid hormone excess. METHODS/DESIGN: Overall,
      110 adult male and female patients with primary hyperparathyroidism will be
      randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50
      mg once daily after dose titration] or placebo, over eight weeks. Each
      participant will undergo detailed clinical assessment, including anthropometric
      evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography,
      kidney function and detailed laboratory determination of biomarkers of bone
      metabolism and cardiovascular disease.The study comprises the following
      exploratory endpoints: mean change from baseline to week eight in (1) parathyroid
      hormone(1-84) as the primary endpoint and (2) 24-h systolic and diastolic
      ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h
      urinary protein/albumin excretion and echocardiographic parameters reflecting
      systolic and diastolic function as well as cardiac dimensions, as secondary
      endpoints. DISCUSSION: In view of the reciprocal interaction between aldosterone
      and parathyroid hormone and the potentially ensuing target organ damage, the
      EPATH trial is designed to determine whether eplerenone, compared to placebo,
      will effectively impact on parathyroid hormone secretion and improve
      cardiovascular, renal and bone health in patients with primary
      hyperparathyroidism. TRIAL REGISTRATION: ISRCTN33941607.

PMID- 22974445
TI  - Can reputation biases influence the outcome and process of making competence
      judgments of a coach?
AB  - The present studies explored the effect of reputational biases on judgments made
      of coach competence and the visual search patterns adopted by individuals when
      generating initial impressions and expectations of a target. In study 1,
      participants (n = 326) observed footage of two coaches prior to making competence
      judgments of them. All participants viewed similar footage for the first coach
      (control) but reputational information was manipulated for the second coach
      (target). In study 2, participants (n = 22) followed the same procedure as study
      1 but also wore a head-mounted eye-tracking system to enable visual search data
      to be collected. Study 1 broadly reported coaches with a "professional"
      reputation to be judged as being significantly more competent across varying
      competence measures compared to coaches with either an "in-training" reputation
      or "no reputation." Study 2 indicated limited differences across the reputational
      conditions in relation to visual fixations. The data indicate that expectations
      of coach competence can be influenced, and largely controlled, by the
      reputational information provided to athletes. While there were limited
      differences in visual search strategies across reputation conditions, suggestions
      for research are made to enable a fuller insight to the interpersonal
      interactions that may facilitate the working association between athletes and
      coaches.

PMID- 22974446
TI  - Low pretreatment serum total testosterone is associated with a high incidence of
      Gleason score 8-10 disease in prostatectomy specimens: data from ethnic Chinese
      patients with localized prostate cancer.
AB  - What's known on the subject? and What does the study add? Previous data from
      clinically localized prostate cancer (PCa) series treated with radical
      prostatectomy (RP) have suggested that low preoperative serum total testosterone
      level is associated with more aggressive PCa; however, the definition of low
      preoperative total testosterone level varied among these studies (from 220 ng/dL
      to 387 ng/dL). Moreover, no relevant data exist in the literature regarding
      ethnic Chinese patients. The study shows that the most widely used threshold for
      low pretreatment total testosterone level (total testosterone < 300 ng/dL) is not
      appropriate for ethnic Chinese patients, because it could not distinguish
      patients with more aggressive PCa from those with less aggressive disease.
      Setting the threshold at the level of total testosterone < 250 ng/dL works
      better, because pretreatment total testosterone < 250 ng/dL is associated with a
      significantly higher incidence of Gleason score 8-10 disease in RP specimens.
      OBJECTIVE: * To investigate the relationship between preoperative serum total
      testosterone level and prognostic factors of Chinese patients with clinically
      localized prostate cancer (PCa). PATIENTS AND METHODS: * A total of 110 patients
      with localized PCa, treated by radical prostatectomy (RP), were included in this
      prospective study. * Clinical and pathological data from each patient were
      collected. Total testosterone was measured on the morning of surgery. * Total
      testosterone levels for each patient were compared using two thresholds:
      threshold 1 (total testosterone <300 ng/dL vs total testosterone >= 300 ng/dL)
      and threshold 2 (total testosterone <250 ng/dL vs total testosterone >= 250
      ng/dL). RESULTS: * The median preoperative total testosterone level was 346
      ng/dL. Gleason scores of <= 6, 7 and >= 8 were found in the RP specimens from 21
      (19.1%), 67 (60.9%) and 22 (20.0%) patients, respectively. * Compared with those
      with low grade disease, patients with high grade disease (Gleason score >= 8) in
      RP specimens had a significantly lower preoperative total testosterone. * When
      comparing 35 patients with hypogonadism with 75 patients with eugonadism,
      classified by threshold 1, no significant relationships were found. * When
      comparing 18 patients with hypogonadism with 92 patients with eugonadism,
      classified by threshold 2, pathological Gleason score >= 8 tumours were more
      common in patients with hypogonadism. CONCLUSION: * Setting the threshold for
      hypogonadism at the level of pretreatment serum total testosterone <250 ng/dL is
      appropriate for ethnic Chinese patients with localized PCa, because patients with
      pretreatment total testosterone <250 ng/dL are associated with a higher incidence
      of Gleason score 8-10 disease in RP specimens.

PMID- 22974447
TI  - Cryoprotective effects of low-density lipoproteins, trehalose and soybean
      lecithin on murine spermatogonial stem cells.
AB  - Spermatogonial stem cells (SSCs) have the ability to self-renew and offer a
      pathway for genetic engineering of the male germ line. Cryopreservation of SSCs
      has potential value for the treatment of male infertility, spermatogonial
      transplantation, and so on. In order to investigate the cryopreservation effects
      of different cryoprotectants on murine SSCs, 0.2 M of low-density lipoproteins
      (LDL), trehalose and soybean lecithin were added to the cryoprotective medium,
      respectively, and the murine SSCs were frozen at -80 degrees C or -196 degrees C.
      The results indicated that the optimal recovery rates of murine SSCs in the
      cryoprotective medium supplemented with LDL, trehalose and soybean lecithin were
      92.53, 76.35 and 75.48% at -80 degrees C, respectively. Compared with freezing at
      -196 degrees C, the optimum temperature for improvement of recovery rates of
      frozen murine SSCs, cryopreservation in three different cryoprotectants at -80
      degrees C, were 17.11, 6.68 and 10.44% respectively. The recovery rates of murine
      SSCs in the cryoprotective medium supplemented with 0.2 M LDL were significantly
      higher than that of other cryoprotectants (P < 0.05). Moreover, the recovery
      rates were demonstrated to be greater at -80 degrees C compared with at -196
      degrees C (P < 0.05). In conclusion, 0.2 M of LDL could significantly protect
      murine SSCs at -80 degrees C. In the freezing-thawing process, LDL is responsible
      for the cryopreservation of murine SSCs because it can form a protective film at
      the surface of membranes. However, more research is needed to evaluate and
      understand the precise role of LDL during the freezing-thawing of SSCs.

PMID- 22974449
TI  - [Not Available].

PMID- 22974448
TI  - Strong contributions from vertical triads to helix-partner preferences in
      parallel coiled coils.
AB  - Pairing preferences in heterodimeric coiled coils are determined by
      complementarities among side chains that pack against one another at the helix
      helix interface. However, relationships between dimer stability and interfacial
      residue identity are not fully understood. In the context of the "knobs-into
      holes" (KIH) packing pattern, one can identify two classes of interactions
      between side chains from different helices: "lateral", in which a line connecting
      the adjacent side chains is perpendicular to the helix axes, and "vertical", in
      which the connecting line is parallel to the helix axes. We have previously
      analyzed vertical interactions in antiparallel coiled coils and found that one
      type of triad constellation (a'-a-a') exerts a strong effect on pairing
      preferences, while the other type of triad (d'-d-d') has relatively little impact
      on pairing tendencies. Here, we ask whether vertical interactions (d'-a-d')
      influence pairing in parallel coiled-coil dimers. Our results indicate that
      vertical interactions can exert a substantial impact on pairing specificity, and
      that the influence of the d'-a-d' triad depends on the lateral a' contact within
      the local KIH motif. Structure-informed bioinformatic analyses of protein
      sequences reveal trends consistent with the thermodynamic data derived from our
      experimental model system in suggesting that heterotriads involving Leu and Ile
      are preferred over homotriads involving Leu and Ile.

PMID- 22974450
TI  - Urinary interleukin-6 excretion reflects mean 24-hour systolic blood pressure in
      type 2 diabetes.
AB  - AIMS: Research into new risk markers for diabetic kidney disease is required. We
      aimed to study 24-hour urinary interleukin- 6 excretion (uIL-6) in type 2
      diabetic patients in relation to organ damage induced by increased blood
      pressure. METHODS: 24-hour uIL-6 and albumin excretion and 24-hour blood pressure
      recording were evaluated in 49 patients with type 2 diabetes and normal renal
      function. Patients with optimized mean 24-hour systolic blood pressure (SBP),
      defined as SBP <= 130 mmHg, and those with uncontrolled SBP (SBP > 130 mmHg) were
      compared. Multiple linear regression analysis was performed to study significant
      contributors to variance in the 24-hour uIL-6 excretion rate. RESULTS: Albumin
      excretion rate (AER) and uIL-6 were significantly correlated (r=0.63; p<0.0001).
      Patients with mean 24-hour SBP above 130 mmHg (n=27) had significantly higher
      mean uIL-6 excretion than those with a mean 24-hour SBP equal to or below 130
      mmHg (n=22) (p=0.009). The strength of the association of uIL-6 with diurnal and
      mean diastolic blood pressure (DBP) was significantly greater than that with AER.
      Mean SBP (p<0.0001) contributed to 25% of AER variance after body mass index,
      age, sex, mean SBP, mean DBP, HbA1c and smoking status were accounted for. Mean
      24-hour SBP (p=0.005) and smoking (p=0.03) contributed to 15% and 9%,
      respectively, of uIL-6 variance. CONCLUSIONS: Increased uIL-6, perhaps by
      reflecting significant tissue damage and remodelling, could be a marker for
      increased mean SBP in type 2 diabetes.

PMID- 22974451
TI  - Increase in the prevalence of overweight and obesity in the pediatric population
      of the province of Alicante (Spain) in the last 10 years.
AB  - INTRODUCTION: Obesity in childhood and adolescence has reached alarming
      proportions in Europe and the United States. As the incidence of childhood
      obesity has increased during last few years, the consequences of obesity in
      children, including type 2 diabetes, hyperlipidemia and cardiovascular disease,
      have also increased. MATERIAL AND METHOD: We performed a cross-sectional
      epidemiological study of a cohort of schoolchildren in the province of Alicante,
      aged 6-11 years old (n=394; 204 boys and 190 girls). Height, weight, body
      perimeters and skinfolds were measured. Obesity was defined according to body
      mass index (BMI), body perimeters and skinfolds>=2 standard deviations or>=97th
      percentile, using the longitudinal study of Zaragoza and Spanish growth data
      provided by the enKid study as the reference populations. We compared our results
      with the study performed in 1993 in the same province. A survey on nutritional
      and exercise habits was also carried out. RESULTS: The prevalence of obesity in
      schoolchildren in the province of Alicante, according to their BMI, ranged from
      13.5% to 18.8%, depending on the growth curves used as a reference. The
      prevalence of overweight and obesity, based on growth and weight growth curves,
      increased from 9.71% to 22.3% and from 8.93% to 18.8% in boys and girls,
      respectively, in the last 10 years in the schoolchildren in the province of
      Alicante. According to our nutritional survey, intake of fruit and vegetables was
      low in this population. Moreover, a clear association was found between obesity
      and lack of physical exercise, this factor being highly important in the
      pathogenesis of childhood obesity. CONCLUSIONS: The prevalence of overweight and
      obesity has increased in Alicante since 1993.

PMID- 22974452
TI  - Hormonal determinants of depression and cognitive function in independently
      living elders.
AB  - OBJECTIVE: To study the potential associations among circulating insulinlike
      growth factor 1 (IGF-1) and adrenal and gonadal steroids with cognitive status
      and depression in a group of independently-living elders. DESIGN: Population
      based cross sectional study. METHODS: A total of 313 individuals (160 women and
      153 men, with a mean age of 76.7+/-7 years) participated in this study. A
      physical examination, assessment of functional capacity, cognitive function,
      depression, educational level and measurement of plasma cortisol,
      dehydroepiandrosterone (DHEA) and its sulphate (DHEAs), testosterone, estradiol,
      and IGF-1 were performed. RESULTS: In women, adrenal steroids showed a negative
      correlation with global cognition (beta=-0.79; p=0.03 for DHEA and beta=-0.27;
      p=0.002 for cortisol). A positive correlation with IGF-1 (beta=0.026; p=0.04) was
      found for cognition in women after adjustment for depression. For memory
      function, DHEA correlated negatively but no relationship with IGF-1 and cortisol
      was observed. No relationships with cognition were observed in men for any of the
      steroids or other hormones studied. Educational level showed the highest
      protective effect (odds ratio [OR] = 6.25) for preserved cognition for both
      sexes; in women, OR for deteriorated cognition with age, DHEA and cortisol were
      1.14, 1.57 and 1.09, respectively. No associations between depression and
      hormonal profile were found in either sex. CONCLUSIONS: Educational level was
      positively associated with cognitive function in independently-living elderly men
      and women, while adrenal steroids were associated with impaired cognition in
      elderly women but not in men. The hormonal milieu seemed to have little or no
      influence on depression in the men and women studied.

PMID- 22974453
TI  - Role of aminopeptidases in the neuroendocrine control of blood pressure in
      experimental animals.
AB  - Control of blood pressure is partially accomplished by several proteolytic
      enzymes included in the renin-angiotensin system. These enzymes produce several
      peptides that form the active components of the system. Study of these enzymes is
      essential for a deep understanding of blood pressure control and could offer the
      possibility of controlling this system pharmacologically. Glutamylaminopeptidase
      converts angiotensin II into angiotensin III, which in turn is converted into
      angiotensin IV by an alanyl or arginyl aminopeptidase. Angiotensin I, through the
      action of aspartyl aminopeptidase, is converted into angiotensin 2-10, which may
      counteract the hypertensive actions of angiotensin II. Angiotensin III is the
      most active form of brain angiotensins and has a tonic stimulatory effect on
      blood pressure. Analysis of glutamyl-aminopeptidase inhibition has allowed the
      development of agents that effectively reduce blood pressure. Moreover, the
      development of aspartyl-aminopeptidase activators could be another goal, with a
      view to designing new antihypertensive agents. Our group has observed that
      unilateral lesions of the nigrostriatal pathway in rat brain produce simultaneous
      modifications in blood pressure and aminopeptidase activities, both in brain and
      plasma, curiously depending on the side of the lesion. This possible interaction
      among blood pressure, aminopeptidase activities and brain asymmetry, which could
      produce a differentiated neuroendocrine response on blood pressure control, may
      help us to understand the deep mechanism by which the brain is able to control
      blood pressure peripherally.

PMID- 22974454
TI  - Effect of diet on the low-grade and chronic inflammation associated with obesity
      and metabolic syndrome.
AB  - Adipose tissue is an active endocrine and paracrine organ that releases a large
      number of cytokines and biomarkers, which are involved in the development of
      chronic diseases. These effects have been attributed to direct or indirect
      mechanisms acting on insulin resistance, inflammation and endothelial
      dysfunction. In addition, the expression and secretion of these biomarkers in
      various tissues can be influenced by dietary patterns, with an effect on
      inflammatory status. In this context, following an energy-balanced diet, moderate
      in carbohydrates, high in oleic and omega-3 fatty acids, and low in saturated and
      trans fatty acids, with high intake of fruits and legumes and moderate alcohol
      consumption, appears to have beneficial effects on the inflammatory state
      associated with obesity and the manifestations of metabolic syndrome. However,
      the long-term impact of habitual intake and the mechanisms involved in distinct
      physiological and pathological conditions remain unclear.

PMID- 22974455
TI  - Abdominal obesity: an indicator of cardiometabolic risk.
AB  - Abdominal obesity (AO), together with insulin resistance, forms the
      pathophysiological basis of metabolic syndrome. Excess visceral adipose tissue
      (VAT) plays a key role in the comorbidity associated with AO. Multiorgan
      steatosis promotes insulin resistance, oxidative stress and inflammation, giving
      rise to endothelial dysfunction and atherosclerosis. Excess VAT leads to a
      metabolic risk profile regardless of body mass index. Recent epidemiological
      studies confirm the need to measure waist circumference when evaluating obese
      patients and to include this value and metabolic syndrome parameters in scales to
      assess cardiometabolic risk. The pathogenic capacity of AO should be taken into
      account when evaluating any condition in which reducing cardiometabolic risk is a
      preventive or therapeutic goal.

PMID- 22974456
TI  - A special case of gestational diabetes mellitus.
AB  - We report the case of a young woman who was diagnosed with monogenic diabetes
      caused by a glucokinase gene mutation during the third trimester of pregnancy,
      requiring a change in treatment plan in comparison with her previous pregnancies.
      We also discuss the implications for obstetric management in patients with
      maturity onset diabetes of the young, type 2 (MODY-2).

PMID- 22974457
TI  - Thyrotoxicosis and low iodine uptake in a woman with graves' disease.
AB  - Thyrotoxicosis factitia is defined as thyrotoxicosis resulting from exogenous
      ingestion of thyroid hormone, usually in patients with a psychiatric disorder.
      Diagnosis can be difficult and this entity should be suspected in patients with
      high free tiroxine (T4) concentrations, low or suppressed thyroglobulin
      concentrations, normal urinary iodide excretion and low or suppressed (131)I
      uptake. To establish the differential diagnosis, thyrotoxicosis factitia must be
      distinguished from several diseases with low (131)I uptake, such as Graves'
      disease, subacute thyroiditis, hyperthyroidism due to excessive iodine intake,
      struma ovarii and metastasis from thyroid cancer. Treatment is based on b
      blockers to reduce symptoms and avoid iatrogeny. We present a case of
      thyrotoxicosis factitia treated in our outpatient clinic.

PMID- 22974458
TI  - Characterization of the sarcoplasmic reticulum Ca-ATPase from rabbit temporalis
      muscle.
AB  - OBJECTIVE: The aim of this work was to isolate the sarcoplasmic reticulum (SR) Ca
      ATPase from rabbit temporalis muscle and to determine the optimal conditions for
      calcium transport and enzymatic activity. DESIGN: SR vesicles were isolated from
      rabbit temporalis muscle by differential centrifugation, the protein composition
      analyzed by electrophoresis and compared to fast-twitch muscle membrane
      suspensions. ELISA was used to determine the sarcoendoplasmic reticulum Ca-ATPase
      (SERCA) isoform. Ca-ATPase activity was determined by a colorimetric method.
      Calcium-binding to the Ca-ATPase, calcium uptake, calcium efflux and
      phosphorylation by P(i) were determined with radioisotopic techniques. RESULTS:
      Sixty five percent of the total protein concentration of SR membranes suspensions
      from rabbit temporalis corresponded to SERCA. Of the total SERCA protein, 64% was
      SERCA 2, 35% was SERCA 1 and less than 1% was SERCA 3. The optimal conditions of
      the SERCA isolated from rabbit temporalis muscle were: pH 7.2, 5 MUM Ca(2+), 100
      MUM EGTA, 90 MUM Mg(2+), 3mM ATP and 100mM KCl and did not differ from fast
      twitch skeletal muscle. The temporalis maximal calcium uptake and Ca-ATPase
      activity were lower but the sensitivity to the specific Ca-ATPase inhibitor
      thapsigargin was higher. Calcium-binding to the enzyme and calcium efflux were
      similar while the phosphorylation of the enzyme by P(i) was lower. CONCLUSION:
      The lower enzymatic activity and calcium transport capability of the Ca-ATPase
      isolated from rabbit temporalis, and the higher sensitivity to inhibitory drugs
      are consistent with the presence of a substantial proportion of SERCA 2, which
      can be expected in other rabbit masticatory muscles.

PMID- 22974459
TI  - Prevalence of childhood and adolescent overweight and obesity in Benue State,
      Nigeria.
AB  - OBJECTIVE: To evaluate demographic variation in the prevalence of overweight (OW)
      and obesity (OB) among 3240 children and adolescents (girls: n = 1714; boys: n =
      1526) aged 9-16 years attending primary and secondary schools in Benue State of
      Nigeria. METHODS: Participants' anthropometric characteristics (body weight,
      stature, body mass index: BMI and lean body mass: LBM) were determined using
      standard protocols. OW and OB were estimated using International Obesity task
      Force diagnostic criteria. Data were analysed with one-way anova and binary
      logistic regression method. RESULTS: Overall, 88.5%, 9.7% and 1.8% of the
      adolescents had normal BMI and were OW and obese, respectively. Prevalence of OW
      was higher among girls (20.3%) than boys (16.2%), whereas a relatively higher
      incidence of OB was noted among the boys (3.5%). Girls in urban areas had a
      significantly higher BMI (t524 = 3.61, P = 0.002) than their rural peers, but the
      rural girls were more significantly OW than their urban counterparts (BMI: t1186
      = 2.506). Logistic regression models assessing the influence of age, gender and
      location on OW/OB in children (alpha(2) (3, N = 1014) = 6.185, P = 0.103) and
      adolescents (alpha(2) (3, N = 2226) = 1.435, P = 0.697) did not turn up
      significant results. In the gender-specific analysis, the younger boys' model was
      also not significant (alpha(2) (2, N = 488) = 1.295, P = 0.523) in contrast to
      the girls' (alpha(2) (2, N = 526) = 15.637, P = 0.0005), thus discriminating
      between OW and healthy weight among the children. Overall, the model explained
      2.9-4.4% of the variance in weight status and correctly classified 76.8% of the
      cases. Age wise, the model yielded a significant odds ratio of 1.49, suggesting
      that the likelihood of being OW increases by a factor of 1.5 with a unit increase
      in age. Also, the likelihood of an urban girl becoming OW or obese was 0.57 times
      that of a rural girl. CONCLUSIONS: In general, girls in urban areas had higher
      prevalence of OW and OB than girls in rural settings. Among the boys, similar but
      less marked trends were found, except that the rural boys tended to be more OW on
      average than their peers in urban areas. In view of its public health
      significance, it is important to periodically evaluate the prevalence of weight
      disorders in children and adolescents so that appropriate preventative strategies
      can be instituted.

PMID- 22974460
TI  - Study of chemical ligation via 17-, 18- and 19-membered cyclic transition states.
AB  - Unprotected S-acylated cysteine isopeptides containing alpha-, beta- or gamma
      amino acid units have been synthesized, and their conversion to native
      hexapeptides by S- to the N-terminus ligations involving 17-, 18- and 19-membered
      cyclic transition states have been demonstrated both experimentally and
      computationally to be more favorable than intermolecular cross-ligations.

PMID- 22974461
TI  - Nursing home administrators' perspectives on a study feedback report: a cross
      sectional survey.
AB  - BACKGROUND: This project is part of the Translating Research in Elder Care (TREC)
      program of research, a multi-level and longitudinal research program being
      conducted in 36 nursing homes in three Canadian Prairie Provinces. The overall
      goal of TREC is to improve the quality of care for older persons living in
      nursing homes and the quality of work life for care providers. The purpose of
      this paper is to report on development and evaluation of facility annual reports
      (FARs) from facility administrators' perspectives on the usefulness,
      meaningfulness, and understandability of selected data from the TREC survey.
      METHODS: A cross sectional survey design was used in this study. The feedback
      reports were developed in collaboration with participating facility
      administrators. FARs presented results in four contextual areas: workplace
      culture, feedback processes, job satisfaction, and staff burnout. Six weeks after
      FARs were mailed to each administrator, we conducted structured telephone
      interviews with administrators to elicit their evaluation of the FARs.
      Administrators were also asked if they had taken any actions as a result of the
      FAR. Descriptive and inferential statistics, as well as content analysis for open
      ended questions, were used to summarize findings. RESULTS: Thirty-one facility
      administrators (representing thirty-two facilities) participated in the
      interviews. Six administrators had taken action and 18 were planning on taking
      action as a result of FARs. The majority found the four contextual areas
      addressed in FAR to be useful, meaningful, and understandable. They liked the
      comparisons made between data from years one and two and between their facility
      and other TREC study sites in their province. Twenty-two indicated that they
      would like to receive information on additional areas such as aggressive
      behaviours of residents and information sharing. Twenty-four administrators
      indicated that FARs contained enough information, while eight found FARs 'too
      short'. Administrators who reported that the FAR contained enough information
      were more likely to take action within their facilities than administrators who
      reported that they needed more information. CONCLUSIONS: Although the FAR was
      brief, the presentation of the four contextual areas was relevant to the majority
      of administrators and prompted them to plan or to take action within their
      facility.

PMID- 22974462
TI  - Structuring of interfacial water on silica surface in cyclohexane studied by
      surface forces measurement and sum frequency generation vibrational spectroscopy.
AB  - We investigated interfacial water, formed by adsorption or phase separation
      (prewetting transition), on a silica surface in water-cyclohexane binary liquids
      using a combination of colloidal probe atomic force microscopy (AFM) and sum
      frequency generation (SFG) vibrational spectroscopy. At 33 +/- 9 ppm water, the
      long-range attraction extending to 19.4 +/- 2.9 nm appeared, which was caused by
      the contact of water layers formed on silica surfaces. The attraction range
      increased with increasing water concentration and reached 97 +/- 17 nm at the
      saturation concentration of water in cyclohexane (C*), indicating that the
      thickness of the water layer formed on silica was ca. 50 nm. The interfacial
      energy between the water adsorption layer and bulk solution (gamma = 79.3 +/- 2.0
      mN/m) was estimated from the pull-off force, and was significantly larger than
      the value for the bulk water/cyclohexane interface (gamma = 50.1 mN/m). SFG
      spectroscopy demonstrated that the interfacial water formed an icelike structure
      at C*. These results indicated that the interfacial water molecules formed an
      icelike ordered structure induced by the hydrogen bonding with surface silanol
      groups, resulting in the free OH groups being more exposed to the bulk solution.
      On the other hand, the water adsorption layer induced by phase separation at
      water concentrations above C* was found to be less ordered and its structure at
      the adsorption layer/bulk interface was almost the same as that of bulk water,
      although its thickness was almost the same as that formed at C*. To our
      knowledge, this is the first report of the observation of liquid adsorption
      layers formed by chemical interaction up to saturation and by the wetting
      transition above saturation, and their differences in the structure and
      properties at the molecular level.

PMID- 22974463
TI  - Intestinal regeneration, residual function and immunological priming following
      rescue therapy after rat small bowel transplantation.
AB  - Clinical evidence suggests that recurrent acute cellular rejection (ACR) may
      trigger chronic rejection and impair outcome after intestinal transplantation. To
      test this hypothesis and clarify underlying molecular mechanisms,
      orthotopic/allogenic intestinal transplantation was performed in rats. ACR was
      allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue
      strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous
      immunosuppression without ACR, with observation for 7/14 and 21 days after
      transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and
      resulted in improved histology and less cellular infiltration. Proinflammatory
      cytokines and chemotactic mediators in the muscle layer were significantly
      reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA)
      were observed with infliximab. Contractile function improved significantly after
      FK506 rescue therapy, with a slight benefit from additional infliximab, but did
      not reach nontransplanted controls. Fibrosis onset was detected in both rescue
      groups by Sirius-Red staining with concomitant increase of the fibrogenic
      mediator VEGF. Recovery from ACR could be attained by both rescue therapy
      regimens, progressing steadily after initiation of immunosuppression. Reversal of
      ACR, however, resulted in early stage graft fibrosis. Additional infliximab
      treatment may enhance physiological recovery of the muscle layer and enteric
      nervous system independent of inflammatory reactions.

PMID- 22974464
TI  - The late steps of plant nonsense-mediated mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality control system that
      identifies and degrades mRNAs containing premature termination codons (PTCs). If
      translation terminates at a PTC, the UPF1 NMD factor binds the terminating
      ribosome and recruits UPF2 and UPF3 to form a functional NMD complex, which
      triggers the rapid decay of the PTC-containing transcript. Although NMD
      deficiency is seedling lethal in plants, the mechanism of plant NMD remains
      poorly understood. To understand how the formation of the NMD complex leads to
      transcript decay we functionally mapped the UPF1 and SMG7 plant NMD factors, the
      putative key players of NMD target degradation. Our data indicate that the
      cysteine-histidine-rich (CH) and helicase domains of UPF1 are only essential for
      the early steps of NMD, whereas the heavily phosphorylated N- and C-terminal
      regions play a redundant but essential role in the target transcript degradation
      steps of NMD. We also show that both the N- and the C-terminal regions of SMG7
      are essential for NMD. The N terminus contains a phosphoserine-binding domain
      that is required for the early steps of NMD, whereas the C terminus is required
      to trigger the degradation of NMD target transcripts. Moreover, SMG7 is a P-body
      component that can also remobilize UPF1 from the cytoplasm into processing bodies
      (P bodies). We propose that the N- and C-terminal phosphorylated regions of UPF1
      recruit SMG7 to the functional NMD complex, and then SMG7 transports the PTC
      containing transcripts into P bodies for degradation. 

PMID- 22974465
TI  - Polarization of host immune responses by helminth-expressed glycans.
AB  - Helminth parasites bias host CD4(+) T helper (Th) cells toward Th2 responses,
      drive alternative activation of macrophages, and expand T regulatory cells.
      Helminth-expressed carbohydrates play critical roles in driving much of this
      immune cell biasing. Studies on helminth glycans have focused on Lewis X, LDN,
      LDN-DF, other fucosylated structures, chitin, tyvelose, and trehalose, which
      interact with host antigen presenting cells (APCs) minimally via C-type lectins
      and/or Toll-like receptors (TLR). Here, we review recent findings on helminth
      glycan activation of APCs via C-type lectin/TLRs and introduce the concept that
      glycosylated helminth molecules require endocytosis to function as immune
      modulators. Second, we describe unpublished data showing that in vivo
      glycoconjugates comprising multiple copies of glycans on carriers are directly
      immune modulatory. Lastly, we discuss the observation that CD14 negatively
      regulates alternative activation of APCs during helminth infection. We close with
      a discussion on the use of immune modulatory glycans as vaccine adjuvants and as
      antiinflammatory therapeutics.

PMID- 22974467
TI  - Insensitivity to scope in contingent valuation studies: new direction for an old
      problem.

PMID- 22974466
TI  - Human rotavirus vaccine RotarixTM provides protection against diverse circulating
      rotavirus strains in African infants: a randomized controlled trial.
AB  - BACKGROUND: Rotaviruses are the most important cause of severe acute
      gastroenteritis worldwide in children <5 years of age. The human, G1P[8]
      rotavirus vaccine RotarixTM significantly reduced severe rotavirus
      gastroenteritis episodes in a Phase III clinical trial conducted in infants in
      South Africa and Malawi. This paper examines rotavirus vaccine efficacy in
      preventing severe rotavirus gastroenteritis, during infancy, caused by the
      various G and P rotavirus types encountered during the first rotavirus-season.
      METHODS: Healthy infants aged 5-10 weeks were enrolled and randomized into three
      groups to receive either two (10 and 14 weeks) or three doses of RotarixTM
      (together forming the pooled RotarixTM group) or three doses of placebo at a
      6,10,14-week schedule. Weekly home visits were conducted to identify
      gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT
      PCR and nucleotide sequencing. The percentage of infants with severe rotavirus
      gastroenteritis caused by the circulating G and P types from 2 weeks post-last
      dose until one year of age and the corresponding vaccine efficacy was calculated
      with 95% CI. RESULTS: Overall, 4939 infants were vaccinated and 4417 (pooled
      RotarixTM = 2974; placebo = 1443) were included in the per protocol efficacy
      cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis
      episodes from the placebo group. This was followed in order of detection by G12
      (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against
      G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:
      6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was
      the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus
      gastroenteritis cases in placebo group. The remaining circulating P types
      comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine
      efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI:
      37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%) CONCLUSIONS: RotarixTM
      vaccine demonstrated efficacy against severe gastroenteritis caused by diverse
      circulating rotavirus types. These data add to a growing body of evidence
      supporting heterotypic protection provided by RotarixTM. TRIAL REGISTRATION
      NUMBER: NCT00241644.

PMID- 22974468
TI  - Japanese children's understanding of notational systems.
AB  - This study examined Japanese children's understanding of two Japanese notational
      systems: hiragana and kanji. In three experiments, 126 3- to 6-year-olds were
      asked to name words written in hiragana or kanji as they appeared with different
      pictures. Consistent with Bialystok (Journal of Experimental Child Psychology,
      2000, Vol. 76, pp. 173-189), 3- and 4-year-olds' identification of written words
      varied according to the picture with which they appeared, and older children
      named the words with different pictures more accurately. The 4-year-olds who
      could read words written in hiragana but could not read words written in kanji
      named both hiragana words and kanji words with different pictures more accurately
      than those who could not read hiragana and kanji words. The interrelationship
      between the symbol-sound relationships and the symbol-referent relationships of
      notational systems is discussed.

PMID- 22974469
TI  - Children's symptoms of posttraumatic stress and depression after a natural
      disaster: comorbidity and risk factors.
AB  - BACKGROUND: The current study examined rates of comorbidity among children's
      symptoms of posttraumatic stress (PTS) and depression after a natural disaster,
      Hurricane Ike. We also compared children with comorbid symptoms to children
      without comorbid symptoms, examining recovery, severity of symptoms, and risk
      factors. METHOD: Children (n=277; 52% girls; 38% Hispanic, 28% White, 19% Black;
      grades 2-4) were assessed at 8 and 15 months postdisaster. Children completed
      measures of PTS and depressive symptoms at both time points and measures of
      exposure and recovery stressors at 8 months postdisaster. RESULTS: At 8 months
      postdisaster, 13% of children reported elevated PTS-only, 11% depression-only,
      and 10% comorbid symptoms of PTS and depression. At 15 months postdisaster, 7% of
      children reported elevated PTS-only, 11% depression-only, and 7% comorbid
      symptoms of PTS and depression. Children with comorbid symptoms of PTS and
      depression had poorer recovery, more severe symptoms, and they reported greater
      exposure and recovery stressors. LIMITATIONS: We lacked information on children's
      predisaster functioning and diagnostic interview of psychological distress
      symptoms. CONCLUSIONS: Children with comorbid symptoms need to be identified
      early postdisaster. Levels of stressors should be monitored postdisaster, as
      highly stressed youth have difficulties recovering and may need help.
      Interventions should be tailored for children with comorbid symptoms of PTS and
      depression.

PMID- 22974471
TI  - Relations between the underlying dimensions of PTSD and major depression using an
      epidemiological survey of deployed Ohio National Guard soldiers.
AB  - BACKGROUND: In the present study, the authors investigated the relationship
      between the underlying symptom dimensions of posttraumatic stress disorder (PTSD)
      and dimensions of major depressive disorder (MDD). METHOD: A sample of 1266 Ohio
      National Guard soldiers with a history of overseas deployment participated and
      were administered the PTSD Checklist (assessing PTSD) and Patient Health
      Questionnaire-9 (assessing depression). RESULTS: Using confirmatory factor
      analysis, results demonstrated that both PTSD's dysphoria and hyperarousal
      factors were more related to depression's somatic than non-somatic factor.
      Furthermore, depression's somatic factor was more related to PTSD's dysphoria
      than hyperarousal factor. LIMITATIONS: Limitations of this study include the use
      of self-report measures and a predominately male military sample. CONCLUSIONS:
      Results indicate that PTSD's dysphoria factor is related to depression
      specifically by way of depression's somatic construct. Given PTSD's substantial
      dysphoria/distress component, these results have implications for understanding
      the nature of PTSD's high comorbidity with depression.

PMID- 22974470
TI  - Topographic and sex-related differences in sleep spindles in major depressive
      disorder: a high-density EEG investigation.
AB  - BACKGROUND: Sleep spindles are believed to mediate several sleep-related
      functions including maintaining disconnection from the external environment
      during sleep, cortical development, and sleep-dependent memory consolidation.
      Prior studies that have examined sleep spindles in major depressive disorder
      (MDD) have not demonstrated consistent differences relative to control subjects,
      which may be due to sex-related variation and limited spatial resolution of
      spindle detection. Thus, this study sought to characterize sleep spindles in MDD
      using high-density electroencephalography (hdEEG) to examine the topography of
      sleep spindles across the cortex in MDD, as well as sex-related variation in
      spindle topography in the disorder. METHODS: All-night hdEEG recordings were
      collected in 30 unipolar MDD participants (19 women) and 30 age and sex-matched
      controls. Topography of sleep spindle density, amplitude, duration, and
      integrated spindle activity (ISA) were assessed to determine group differences.
      Spindle parameters were compared between MDD and controls, including analysis
      stratified by sex. RESULTS: As a group, MDD subjects demonstrated significant
      increases in frontal and parietal spindle density and ISA compared to controls.
      When stratified by sex, MDD women demonstrated increases in frontal and parietal
      spindle density, amplitude, duration, and ISA; whereas MDD men demonstrated
      either no differences or decreases in spindle parameters. LIMITATIONS: Given the
      number of male subjects, this study may be underpowered to detect differences in
      spindle parameters in male MDD participants. CONCLUSIONS: This study demonstrates
      topographic and sex-related differences in sleep spindles in MDD. Further
      research is warranted to investigate the role of sleep spindles and sex in the
      pathophysiology of MDD.

PMID- 22974472
TI  - A randomized, double-blind, placebo-controlled trial of citicoline for bipolar
      and unipolar depression and methamphetamine dependence.
AB  - BACKGROUND: Methamphetamine use disorders are common and severe problems. Persons
      with mood disorders, particularly bipolar disorder, have high rates of substance
      use disorders. We previously reported promising findings on drug use, memory and
      study retention in patients with a history of mania and cocaine dependence given
      the nutritional supplement citicoline. In the current proof-of-concept study, we
      examined citicoline in bipolar or unipolar depression and methamphetamine
      dependence. METHODS: Sixty adults with bipolar depression or major depressive
      disorder and methamphetamine dependence were randomized to citicoline
      (2000mg/day) or placebo for 12 weeks. Mood was assessed using Inventory of
      Depressive Symptomatology-Clinician Version (IDS-C), and cognition with the
      Hopkins Auditory Verbal Learning Test (HVLT). Drug use was assessed by urine drug
      screens. RESULTS: An ANCOVA of the intent-to-treat sample showed that those
      receiving citicoline (n=28) had a statistically significantly greater improvement
      in IDS-C scores than those receiving placebo (n=20). Survival in the study was
      significantly longer and completion rates significantly greater with citicoline
      than placebo. No significant differences were observed in memory or
      methamphetamine use. Citicoline was well tolerated. LIMITATIONS: Sample
      heterogeneity and small sample size were limitations. CONCLUSIONS: To our
      knowledge this is the first placebo-controlled trial in a dual diagnosis sample
      with methamphetamine use disorders. Findings suggest that citicoline may have
      antidepressant properties in this population. Greater treatment retention with
      citicoline is also noteworthy in a patient population with substance dependence.
      Larger trials targeting depressive symptoms and treatment retention seem
      warranted.

PMID- 22974473
TI  - Effect of the phosphodiesterase-5 inhibitor zaprinast on ischemia-reperfusion
      injury in rats.
AB  - PURPOSE: The cardiac and renal protective effects of phosphodiesterase-5 (PDE-5)
      inhibitors against ischemia-reperfusion injury have recently been demonstrated in
      animal studies. We evaluated the effect of pretreatment with the PDE-5 inhibitor
      zaprinast on warm renal ischemia in a rat model. METHODS: Female Sprague-Dawley
      rats underwent concomitant right nephrectomy and left renal hilar occlusion for
      30 minutes. Twelve animals were equally divided into three groups: Group 1
      received no pharmacologic pretreatment, group 2 was pretreated with zaprinast 10
      mg/kg, and group 3 was pretreated with zaprinast 20 mg/kg. Zaprinast was
      dissolved in 25% dimethyl sulfoxide and given as a single intraperitoneal
      injection 30 minutes before surgery. Serum blood urea nitrogen (BUN) and
      creatinine levels, histopathology, and TUNEL staining for apoptosis were assessed
      24 hours postoperatively. RESULTS: The mean creatinine level for groups 1, 2, and
      3 was 0.73 mg/dL, 0.55 mg/dL, and 0.38 mg/dL, respectively. These values were not
      statistically different (P=0.099). The mean BUN levels of 35.8 mg/dL for group 1,
      27.3 mg/dL for group 2, and 23.3 mg/dL for group 3 were also statistically
      similar (P=0.278). There were no objective differences in histopathologic
      evaluation or TUNEL staining between the groups. CONCLUSION: This study did not
      demonstrate a beneficial effect of zaprinast pretreatment on renal parameters
      after warm ischemic injury.

PMID- 22974475
TI  - Size-selective 2D ordering of gold nanoparticles using surface topography of self
      assembled diamide template.
AB  - Size-selective organization of ~2 nm dodecanethiol stabilized gold nanoparticles
      (AuNPs) into periodic 1D arrays by using the surface topographical features of a
      soft template is described. The template consists of micrometer length nanotapes
      organized into nanosheets with periodic valleys running along their length and is
      generated by the hierarchical self-assembly of a diamide molecule (BHPB) in
      cyclohexane. The AuNP ordering achieved simply by mixing the preformed template
      with the readily available ~2 nm dodecanethiol stabilized AuNPs is comparable to
      those obtained using programmable DNA and functional block copolymers. The
      observed periodicity of the AuNP arrays provided valuable structural clues about
      the organization of nanotapes into nanosheets. Self-assembling BHPB molecules in
      the presence of AuNPs by heating and cooling the two components led to a
      comparatively disordered organization because the template structure was changed
      under these conditions. Moreover, the template could not order larger AuNPs (~5
      nm) into a similar 1D array, owing to the steric restriction imposed by the
      dimension of the valleys on the template. Interestingly, this geometric
      constraint led to AuNP size sorting when a polydisperse sample (2.5 +/- 0.9 nm)
      was used for organization, with AuNPs attached to the template edges being larger
      (>=2.2 +/- 0.9 nm) than those associated to the inner valleys (1.6 +/- 0.8 nm).
      This is a unique example of size-sorting induced by the surface topographical
      features of a soft template.

PMID- 22974474
TI  - Development of a new humanized mouse model to study acute inflammatory arthritis.
AB  - BACKGROUND: Substantial advances have been generated in understanding the
      pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like
      disease have provided great insights into the molecular mechanism of inflammatory
      arthritis due to the use of genetically deficient or transgenic mice. However,
      these studies are limited by differences that exist between human and murine
      immune systems. Thus, the development of an animal model that utilizes human
      immune cells, will afford the opportunity to study their function in the
      initiation and propagation of inflammatory arthritis. METHODS: One to two-day old
      irradiated NOD-scid IL2rgamma(null) (NSG) mice were reconstituted with human
      CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and
      circulating antibodies were determined by ELISA. Arthritis was induced by
      injecting complete Freund's adjuvant into knee or ankle joints. Mice were also
      treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed
      histologically. RESULTS: Humanized mice were established with high reconstitution
      rates and were able to spontaneously produce human immunoglobulins as well as
      specific IgG in response to immunization. Intraperitoneal injection of
      thioglycolate or injection of complete Freund's adjuvant into joints resulted in
      migration of human immune cells to the injected sites. Arthritic humanized mice
      treated with Etanercept had markedly less inflammation, which was associated with
      decreased total numbers of human CD45+ cells, including human lymphocytes and
      neutrophils. CONCLUSIONS: The humanized mouse model is a new model to study
      inflammatory arthritis disease using human leukocytes without rejection of
      engrafted tissue. Future studies may adapt this system to incorporate RA patient
      cord blood and develop a chimeric animal model of inflammatory arthritis using
      genetically predisposed immune cells.

PMID- 22974476
TI  - Molecular events in endometrial carcinosarcomas and the role of high mobility
      group AT-hook 2 in endometrial carcinogenesis.
AB  - The molecular events implicated in the development of endometrial carcinosarcoma
      remain poorly understood. Using complementary DNA microarrays, we analyzed a
      group of 15 endometrial carcinosarcomas and compared their gene expression
      profiles with those obtained from a group of 23 endometrioid endometrial
      carcinomas. We demonstrated changes in the expression of genes modulating
      processes such as the epithelial to mesenchymal transition, muscle
      differentiation, the expression of cancer/testis antigens, and immune response in
      endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an
      embryonic nuclear factor that mediates epithelial to mesenchymal transition in
      various tumor models, and it was among the genes overexpressed in endometrial
      carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in
      54% of endometrial carcinosarcomas by quantitative real time-polymerase chain
      reaction and immunohistochemistry. Moreover, we found a significant inverse
      correlation between the expression of high mobility group AT-hook 2 and let-7b, a
      member of the let-7 family of microRNAs that represses high mobility group AT
      hook 2 expression. These changes were also associated with overexpression of
      Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer
      progression and metastasis. Finally, high mobility group AT-hook 2
      overexpression, which was detected in less than 3% of endometrioid endometrial
      carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples).
      This pattern of expression, restricted to nonendometrioid carcinomas and
      endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in
      endometrial carcinogenesis that is associated with aggressive phenotypes and
      points to its potential use as a marker to distinguish between endometrioid and
      nonendometrioid tumors.

PMID- 22974477
TI  - IgG4-related paratesticular pseudotumor in a patient with autoimmune pancreatitis
      and retroperitoneal fibrosis: an extrapancreatic manifestation of IgG4-related
      disease.
AB  - In this report, we describe the first case of a patient with an IgG4-related
      paratesticular pseudotumor. He had histologically proven autoimmune pancreatitis,
      then later developed a scrotal mass. The orchiectomy specimen revealed that this
      was a paratesticular pseudotumor with histopathologic and immunohistochemistry
      findings characteristic of IgG4-related disease. Paratesticular pseudotumors are
      uncommon causes of intrascrotal masses and have an unexplained pathogenesis. A
      variety of genitourinary manifestations of IgG4-related disease including IgG4
      related tubulointerstitial nephritis, IgG4-related ureteral pseudotumors, and
      IgG4-related prostatitis has been previously reported. The current case
      highlights the need to have a high index of suspicion for IgG4-tissue
      infiltration in patients with known autoimmune pancreatitis, particularly those
      with a pseudotumor.

PMID- 22974478
TI  - Snail promotes lymph node metastasis and Twist enhances tumor deposit formation
      through epithelial-mesenchymal transition in colorectal cancer.
AB  - Snail and Twist, transcriptional repressors of E-cadherin as well as inducers of
      epithelial-mesenchymal transition, play pivotal roles in tumor invasion and
      metastasis. We investigated the expression of Snail, Twist, and E-cadherin by
      immunohistochemistry in 193 colorectal cancers, including 79 with positive lymph
      nodes, 36 with tumor deposits, 39 with both, and 39 with no metastases. Snail was
      expressed to a greater extent in the group with positive lymph nodes (68.4%),
      whereas Twist was overexpressed in patients with other metastases (75.0%).
      Ectopic expression of Snail and Twist correlated with reduced membranous
      expression of E-cadherin. Importantly, Snail overexpression correlated
      significantly with lymph node metastasis (P < .0001), whereas Twist up-regulation
      correlated strongly with other metastases (P < .0001). Multivariate logistic
      regression analysis showed that Snail was an independent predictor of lymph node
      metastasis (odds ratio, 4.445; 95% confidence interval, 2.250-8.781; P < .0001),
      whereas Twist displayed predictive value for metastasis formation (odds ratio,
      5.606; 95% confidence interval, 2.829-11.111; P < .0001), suggesting that lymph
      node and other metastases may follow different signaling pathways. In conclusion,
      ectopic expression of Snail and Twist contributed to lymph node and disseminated
      metastasis, respectively, by reducing E-cadherin expression, providing a novel
      role for Snail and Twist in the progression of colorectal cancer.

PMID- 22974479
TI  - Expression of Twist enhances risk of poor oncologic outcome in patients with
      stage Ib to II cervical carcinoma with lymphovascular space involvement.
AB  - Twist, a basic helix-loop-helix transcription factor, promotes cancer cell
      epithelial-mesenchymal transition and metastasis. Here, we aimed to examine the
      association between Twist expression and lymphovascular space involvement for
      early-stage cervical carcinoma. Paraffin sections from 90 patients with stage Ib
      to IIb cervical carcinoma were immunostained with Twist antibody, and the
      staining intensities were semiquantitatively evaluated. Of the 90 cervical
      carcinoma specimens examined in this study, 51 (56.7%) were negative for Twist
      and 39 (43.3%) were positive for Twist immunoreactivity. The 5-year overall
      survival rates of patients in the Twist-negative and Twist-positive groups were
      98.0% and 75.8%, respectively. Univariate and multivariate analyses demonstrated
      that Twist expression was an independent prognostic factor for overall survival
      and recurrence-free survival (univariate: P = .0069 [overall survival], P = .0092
      [recurrence-free survival]: multivariate: P = .0118 [overall survival], P = .0118
      [recurrence-free survival]). On stratifying based on the negative lymphovascular
      space involvement status, the overall survival and recurrence-free survival of
      patients in the Twist-negative group was the same as that of those in the Twist
      positive group (log-rank: P = .262 [recurrence-free survival], P = .899 [overall
      survival]). In contrast, with lymphovascular space involvement, a significantly
      poorer recurrence-free survival was predicted for patients in the Twist-positive
      group compared with that in the Twist-negative group (P = .0021). Twelve (75.0%)
      of 16 patients showing recurrence belonged to the Twist-positive group, and 83.3%
      (10/12) of them experienced recurrence in distant organs or the peritoneal
      cavity. This study suggested that the assessment of the Twist immunoreactivity
      and lymphovascular space involvement may distinguish high- from low-risk patients
      with locally invasive cervical carcinoma.

PMID- 22974480
TI  - Circumcision with a novel disposable device in Chinese children: a randomized
      controlled trial.
AB  - OBJECTIVES: To compare the outcomes and complications of three methods of
      circumcision in a Chinese pediatric population. METHODS: A total of 120 children
      were randomly assigned to three groups. Group I was submitted to circumcision
      using the Shenghuan disposable device according to Yan's method; group II was
      submitted to circumcision using the same device, but according to Peng's methods;
      group III was operated on by using the conventional scalpel/suture technique. The
      three groups were compared mainly by the following outcomes: duration of surgery,
      intraoperative bleeding, postoperative pain, cosmetic effect, and the rates of
      edema, dehiscence, scarring, adhesion and infection. RESULTS: Groups I and II had
      less intraoperative bleeding. In terms of the duration of surgery, group I was
      the quickest. Pain scores in using the Shenghuan disposable device were higher at
      6 h after surgery compared with the conventional scalpel/suture technique. The
      percentage of patients using paracetamol in group II was higher than that in
      group III at 12 h after surgery. Other complications were similar, and all three
      groups had successful outcomes. CONCLUSIONS: Circumcision using the Shenghuan
      disposable device represents a safer and time-saving option compared with the
      conventional scalpel/suture technique, with better cosmetic outcomes. Yan's
      method seems to be better than Peng's method when using the Shenghuan disposable
      device for circumcision in children.

PMID- 22974482
TI  - [Red lower limb].

PMID- 22974481
TI  - Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf
      extracts.
AB  - BACKGROUND: Plants play a significant role in maintaining human health and
      improving the quality of human life. They serve humans well as valuable
      components of food, as well as in cosmetics, dyes, and medicines. In fact, many
      plant extracts prepared from plants have been shown to exert biological activity
      in vitro and in vivo. The present study explored antioxidant and antigenotoxic
      effects of Daphne gnidium leaf extracts. METHODS: The genotoxic potential of
      petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid
      (TOF) enriched extracts from leaves of Daphne gnidium, was assessed using
      Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was
      tested using the "SOS chromotest test". Antioxidant activities were studied using
      non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase. RESULTS:
      None of the different extracts produced a genotoxic effect, except TOF extract at
      the lowest tested dose. Our results showed that D. gnidium leaf extracts possess
      an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl
      acetate and TOF extracts were the most effective in inhibiting xanthine oxidase
      activity. While, methanol extract was the most potent superoxide scavenger when
      tested with the NBT/Riboflavine assay. CONCLUSIONS: The present study has
      demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic
      effects. These activities could be ascribed to compounds like polyphenols and
      flavonoid. Further studies are required to isolate the active molecules.

PMID- 22974483
TI  - [Hepatomegaly in a 62-year-old woman].

PMID- 22974484
TI  - Tips and pearls for "true" dextroposition of the aorta in tetralogy of Fallot.
AB  - Infundibular stenosis may develop secondary to ventricular septal defect, and
      transannular patch plasty can affect mortality and morbidity rates. Therefore,
      dextroposition of the aorta has been investigated in order to eliminate
      discrepancies in the literature. Figures and illustrations from the selected
      references have been investigated and "actual dextroposition of the aorta" has
      been evaluated as far as the aorta is visible. A careful examination of these
      figures revealed the following tips and pearls for accurate diagnosis of
      dextroposition of the aorta: Aorta and ventricular septal defect should be
      adjacent for a "true" dextroposition of the aorta; the plane where the aorta
      exits from the ventricle should penetrate the plane of the ventricular septal
      defect towards the right ventricle; if the aorta and ventricular septal defect
      intersect at one edge, the aorta may seem to be dextroposed; new diagnostic
      modalities are necessary to evaluate the actual dextroposition status of the
      aorta for the proper planning of treatment.

PMID- 22974486
TI  - Stroke care in Central Eastern Europe: current problems and call for action.
AB  - Stroke is a major medical problem and one of the leading causes of mortality and
      disability all over in Europe. However, there are significant East-West
      differences in stroke care as well as in stroke mortality and morbidity rates.
      Central and Eastern European countries that formerly had centralized and
      socialist health care systems have serious and similar problems in organizing
      health and stroke care 20 years after the political transition. In Central and
      Eastern Europe, stroke is more frequent, the mortality rate is higher, and the
      victims are younger than in Western Europe. High-risk patients live in worse
      environmental conditions, and the socioeconomic consequences of stroke further
      weaken the economic development of these countries. To address these issues, a
      round table conference was organized. The main aim of this conference was to
      discuss problems to be solved related to acute and chronic stroke care in Central
      and Eastern European countries, and also, to exchange ideas on possible
      solutions. In this article, the discussed problems and possible solutions will be
      summarized, and introduce 'The Budapest Statement of Stroke Experts of Central
      and Eastern European countries'.

PMID- 22974485
TI  - Feedback reporting of survey data to healthcare aides.
AB  - BACKGROUND: This project occurred during the course of the Translating Research
      in Elder Care (TREC) program of research. TREC is a multilevel and longitudinal
      research program being conducted in the three Canadian Prairie Provinces of
      Alberta, Saskatchewan, and Manitoba. The main purpose of TREC is to increase
      understanding about the role of organizational context in influencing knowledge
      use in residential long-term care settings. The purpose of this study was to
      evaluate healthcare aides' (HCAs) perceptions of a one-page poster designed to
      feed back aggregated data (including demographic information and perceptions
      about influences on best practice) from the TREC survey they had recently
      completed. METHODS: A convenience sample of 7 of the 15 nursing homes
      participating in the TREC research program in Alberta were invited to
      participate. Specific facility-level summary data were provided to each facility
      in the form of a one-page poster report. Two weeks following delivery of the
      report, a convenience sample of HCAs was surveyed using one-to-one structured
      interviews. RESULTS: One hundred twenty-three HCAs responded to the evaluation
      survey. Overall, HCAs' opinions about presentation of the feedback report and the
      understandability, usability, and usefulness of the content were positive. For
      each report, analysis of data and production and inspection of the report took up
      to one hour. Information sessions to introduce and explain the reports averaged
      18 minutes. Two feedback reports (minimum) were supplied to each facility at a
      cost of CAN$2.39 per report, for printing and laminating. CONCLUSIONS: This study
      highlights not only the feasibility of producing understandable, usable, and
      useful feedback reports of survey data but also the value and importance of
      providing feedback to survey respondents. More broadly, the findings suggest that
      modest strategies may have a positive and desirable effect in participating
      sites.

PMID- 22974487
TI  - Activation of R-mediated innate immunity and disease susceptibility is affected
      by mutations in a cytosolic O-acetylserine (thiol) lyase in Arabidopsis.
AB  - O-acetylserine (thiol) lyases (OASTLs) are evolutionarily conserved proteins
      among many prokaryotes and eukaryotes that perform sulfur acquisition and
      synthesis of cysteine. A mutation in the cytosolic OASTL-A1 protein ONSET OF LEAF
      DEATH3 (OLD3) was previously shown to reduce the OASTL activity of the old3-1
      protein in vitro and cause auto-necrosis in specific Arabidopsis accessions. Here
      we investigated why a mutation in this protein causes auto-necrosis in some but
      not other accessions. The auto-necrosis was found to depend on Recognition of
      Peronospora Parasitica 1 (RPP1)-like disease resistance R gene(s) from an
      evolutionarily divergent R gene cluster that is present in Ler-0 but not the
      reference accession Col-0. RPP1-like gene(s) show a negative epistatic
      interaction with the old3-1 mutation that is not linked to reduced cysteine
      biosynthesis. Metabolic profiling and transcriptional analysis further indicate
      that an effector triggered-like immune response and metabolic disorder are
      associated with auto-necrosis in old3-1 mutants, probably activated by an RPP1
      like gene. However, the old3-1 protein in itself results in largely neutral
      changes in primary plant metabolism, stress defence and immune responses.
      Finally, we showed that lack of a functional OASTL-A1 results in enhanced disease
      susceptibility against infection with virulent and non-virulent Pseudomonas
      syringae pv. tomato DC3000 strains. These results reveal an interaction between
      the cytosolic OASTL and components of plant immunity. 

PMID- 22974488
TI  - Electrospun nanofibrous membranes surface-decorated with silver nanoparticles as
      flexible and active/sensitive substrates for surface-enhanced Raman scattering.
AB  - The development of novel nanomaterials with well-controlled
      morphologies/structures to achieve excellent activities/sensitivities in surface
      enhanced Raman scattering (SERS) is crucial in advancing the high-performance
      SERS detections of chemical and biological species. In this study, amidoxime
      surface-functionalized polyacrylonitrile (ASFPAN) nanofibrous membranes surface
      decorated with silver nanoparticles (Ag NPs) were prepared via the technique of
      electrospinning followed by the method of seed-mediated electroless plating. High
      SERS activities/sensitivities were observed from the ASFPAN-Ag NPs nanofibrous
      membranes, while the density and size of Ag NPs had an important impact on the
      SERS activity/sensitivity. The results confirmed that the enhancement of Raman
      signals is due to the presence of hot spots between/among Ag NPs on the nanofiber
      surfaces. Electrospun nanofibrous membranes surface-decorated with Ag NPs were
      mechanical flexible/resilient and could be used as highly active/sensitive SERS
      substrates for a broad range of applications.

PMID- 22974489
TI  - Genotype-dependent consequences of traumatic stress in four inbred mouse strains.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops in
      predisposed individuals following a terrifying event. Studies on isogenic animal
      populations might explain susceptibility to PTSD by revealing associations
      between the molecular and behavioural consequences of traumatic stress. Our study
      employed four inbred mouse strains to search for differences in post-stress
      response to a 1.5-mA electric foot shock. One day to 6 weeks after the foot shock
      anxiety, depression and addiction-like phenotypes were assessed. In addition,
      expression levels of selected stress-related genes were analysed in hippocampus
      and amygdala. C57BL/6J mice exhibited up-regulation in the expression of Tsc22d3,
      Nfkbia, Plat and Crhr1 genes in both brain regions. These alterations were
      associated with an increase of sensitized fear and depressive-like behaviour over
      time. Traumatic stress induced expression of Tsc22d3, Nfkbia, Plat and Fkbp5
      genes and developed social withdrawal in DBA/2J mice. In 129P3/J strain, exposure
      to stress produced the up-regulation of Tsc22d3 and Nfkbia genes and enhanced
      sensitivity to the rewarding properties of morphine. Whereas, SWR/J mice
      displayed increase only in Pdyn expression in the amygdala and had the lowest
      conditioned fear. Our results reveal a complex genetic background of phenotypic
      variation in response to stress and indicate the SWR/J strain as a valuable model
      of stress resistance. We found potential links between the alterations in
      expression of Tsc22d3, Nfkbia and Pdyn, and different aspects of susceptibility
      to stress. 

PMID- 22974491
TI  - The association between substance use disorders and mortality among a cohort of
      Veterans with posttraumatic stress disorder: variation by age cohort and
      mortality type.
AB  - BACKGROUND: Prior studies of Veterans have linked posttraumatic stress disorder
      (PTSD) with an increased risk of mortality. Other studies of Veterans have found
      that substance use disorders (SUDs) are associated with an excess risk of
      mortality among those with psychiatric disorders. It is not known whether having
      an SUD increases the risk of mortality among Veterans with PTSD, and whether the
      association differs by mortality type or varies by age cohort. METHODS: A cohort
      of patients who received Veterans Health Administration services during fiscal
      year (FY) 2004 and diagnosed with PTSD (n=272,509) were followed from FY 2005
      through FY 2007 for the main outcomes of mortality and cause of death. RESULTS:
      SUD was positively associated with mortality during follow-up (adjusted hazards
      ratio: 1.70; 95% confidence interval: 1.64, 1.77). SUD was a stronger predictor
      of non-injury-related mortality for the <45 years group compared with the 45-64
      or >=65 group. SUD predicted injury-related mortality for all age groups.
      CONCLUSIONS: Among Veterans with PTSD, the association between SUD and mortality
      was most pronounced for the youngest age group, which included Iraq/Afghanistan
      Veterans. For older age groups, which included Vietnam-era Veterans, SUD was a
      greater predictor of injury-related mortality. The findings could be useful for
      identifying PTSD patients at excess risk of mortality.

PMID- 22974490
TI  - Factors associated with history of non-fatal overdose among young nonmedical
      users of prescription drugs.
AB  - OBJECTIVES: The current study examines the prevalence and correlates of lifetime
      non-fatal overdose (OD) involving the nonmedical use of prescription opioids and
      tranquilizers among a sample of high-risk young adults in New York, NY and Los
      Angeles, CA. METHODS: Data were derived from a cross-sectional study of 16-25
      year old nonmedical users of prescription drugs (n=596). Unadjusted associations
      between OD history and socio-demographic and drug use variables were investigated
      in bivariate logistic regression models. Multivariate logistic regression models
      identified correlates of non-fatal OD. RESULTS: Lifetime prevalence of non-fatal
      overdose involving prescription opioids and/or tranquilizers was 23.6%. Factors
      associated with increased risk of non-fatal overdose included lower social class
      while growing up (OR: 1.81, 95% CI: [1.15, 2.83], p<0.01), having ever received
      care at a psychiatric hospital (OR: 1.79, 95% CI: [1.12, 2.85], p<0.05), ever
      witnessing a family member OD on drugs (OR: 1.59, 95% CI: [1.02, 2.50], p<0.05),
      being prescribed tranquilizers (OR: 2.07, 95% CI: [1.29, 4.27], p<0.01), ever
      snorting or sniffing opioids (OR: 2.51, 95% CI: [1.48, 4.27], p<0.001), injecting
      tranquilizers (OR: 3.09, 95% CI: [1.61, 5.93], p<0.001), and past 90-day
      injection drug use (OR: 1.68, 95% CI: [1.03, 2.74], p<0.05). Participants who
      reported past 90-day stimulant misuse had lower odds of reporting OD compared to
      those who were not recent stimulant users (OR: 0.60, 95% CI: [0.38-0.96],
      p<0.05). CONCLUSIONS: This study documents the high prevalence of experiencing
      non-fatal overdose among young nonmedical users of prescription drugs. Results
      could inform overdose prevention efforts throughout the U.S.

PMID- 22974492
TI  - Increase in susceptibility to insecticides with aging of wild Anopheles gambiae
      mosquitoes from Cote d'Ivoire.
AB  - BACKGROUND: Appropriate monitoring of vector insecticide susceptibility is
      required to provide the rationale for optimal insecticide selection in vector
      control programs. METHODS: In order to assess the influence of mosquito age on
      susceptibility to various insecticides, field-collected larvae of An. gambiae
      s.l. from Tiassale were reared to adults. Females aged 1, 2, 3, 5 and 10 days
      were exposed to 5 insecticides (deltamethrin, permethrin, DDT, malathion and
      propoxur) using WHO susceptibility test kits. Outcome measures included the LT50
      (exposure time required to achieve 50% knockdown), the RR (resistance ratio, i.e.
      a calculation of how much more resistant the wild population is compared with a
      standard susceptible strain) and the mortality rate following 1 hour exposure,
      for each insecticide and each mosquito age group. RESULTS: There was a positive
      correlation between the rate of knockdown and mortality for all the age groups
      and for all insecticides tested. For deltamethrin, the RR50 was highest for 2 day
      old and lowest for 10 day old individuals. Overall, mortality was lowest for 2
      and 3 day old individuals and significantly higher for 10 day old individuals (P
      < 0.05). With permethrin, the RR50 was highest for 1 to 3 day old individuals and
      lowest for 10 day old individuals and mortality was lowest for 1 to 3 day old
      individuals, intermediate for 5 day old and highest for 10 day old individuals.
      DDT did not display any knockdown effect and mortality was low for all mosquito
      age groups (<7%). With malathion, the RR50 was low (1.54 - 2.77) and mortality
      was high (>93%) for all age groups. With propoxur, no knockdown effect was
      observed for 1, 2 and 3 day old individuals and a very low level of mortality was
      observed (< 4%), which was significantly higher for 5 and 10 day old individuals
      (30%, P < 0.01). CONCLUSION: Results indicate that for An. gambiae s.l. adults
      derived from wild-collected larvae, there was an influence of age on insecticide
      susceptibility status, with younger individuals (1 to 3 days old) more resistant
      than older mosquitoes. This indicates that the use of 1 - 2 day old mosquitoes in
      susceptibility assays as recommended by the WHO should facilitate detection of
      resistance at the stage where the highest rate of the resistance phenotype is
      present.

PMID- 22974493
TI  - Purification and characterization of carbonic anhydrase from sheep kidney and
      effects of sulfonamides on enzyme activity.
AB  - Carbonic anhydrase (CA, EC: 4.2.1.1) was purified from sheep kidney by affinity
      chromatography on a Sepharose 4B-tyrosine-sulfanilamide column. By means of two
      consecutive procedures, the enzyme (sCA) was purified 227.61-fold with a yield of
      60.75%, and a specific activity of 838.89U/mg proteins. The optimum temperature,
      ionic strength and pH were determined to be 35 degrees C, 20mM and 8.5,
      respectively. The molecular weight determined by SDS-PAGE was found to be 29kDa.
      The kinetic parameters, KM and Vmax values were determined for the 4-nitrophenyl
      acetate (p-NpA) hydrolysis reaction. Some sulfonamides were tested as inhibitors
      against the purified CAs enzyme. The Ki constants for benzenesulfonamide (1),
      sulfanilamide (2), mafenide (3), 4-(2-aminoethyl) benzenesulfonamide (4), 4
      methyl-benzenesulfonamide (5), 2-bromo-benzenesulfonamide (6), naphthalene-2
      sulfonamide (7), 4-amino-6-chlorobenzene-1,3-disulfonamide (8) and saccharin (9)
      were in the range 1.348-69.31MUM.

PMID- 22974494
TI  - Mindfulness for paranoid beliefs: evidence from two case studies.
AB  - BACKGROUND: Emerging evidence suggests that mindfulness can be beneficial for
      people with distressing psychosis. This study examined the hypothesis that for
      people with persecutory delusions in the absence of voices, mindfulness training
      would lead to reductions in conviction, distress, preoccupation and impact of
      paranoid beliefs, as well as anxiety and depression. METHOD: Two case studies are
      presented. Participants completed measures of mindfulness, anxiety and depression
      at baseline, end of therapy and 1 month follow-up, and bi-weekly ratings of their
      paranoid belief on the dimensions of conviction, preoccupation, distress and
      impact. RESULTS: Ratings of conviction, distress, impact and preoccupation, and
      measures of anxiety and depression, reduced for both participants from baseline
      to end of intervention. Improvements in mindfulness of distressing thoughts and
      images occurred for both participants. These gains were maintained at 1 month
      follow-up. CONCLUSIONS: Findings suggest that mindfulness training can impact on
      cognition and affect specifically associated with paranoid beliefs, and is
      potentially relevant to both Poor Me and Bad Me paranoia.

PMID- 22974495
TI  - The quality, breadth, and timeliness of content updating vary substantially for
      10 online medical texts: an analytic survey.
AB  - OBJECTIVE: To evaluate the quality of evidence reporting, breadth of coverage,
      and timeliness of content updating of 10 selected online medical texts. STUDY
      DESIGN AND SETTING: Each text was assessed for quality based on an 11-item scale,
      which included items related to editorial policy and updating, appraisal, and
      transparent incorporation of newly published clinical research and evidence-based
      guidelines. Breadth of coverage was determined by the percentage of 60 randomly
      selected International Classification of Diseases 10 (ICD-10) codes covered by
      each of the texts. The same 60 ICD-10 codes were used to obtain a sample of topic
      chapters for the assessment of timeliness of updates. RESULTS: Quality scores
      ranged from a high of 9 of 11 points (Clinical Evidence) to a low of 0 of 11
      points (PEPID), with a mean score of 6.7. Breadth of coverage ranged from 83% of
      randomly selected topics covered (UpToDate) to 25% (Clinical Evidence), with 6 of
      10 texts covering 60% or more; average coverage across all texts was 57%.
      Variability was also observed with regard to average time since last content
      update, ranging from 3.5 (DynaMed) to 29 months (First Consult), with an average
      time since update of 12.4 months. CONCLUSION: No single resource was ideal and
      those seeking answers to clinical questions are well-advised not to rely solely
      on a single point-of-care product.

PMID- 22974496
TI  - Good test-retest reproducibility for an instrument to capture self-reported
      melanoma risk factors.
AB  - OBJECTIVE: To examine the test-retest reliability and validity of self-reported
      items capturing phenotypic characteristics and sun exposure measures in the
      baseline survey instrument used for a prospective study of skin cancer and
      melanoma. STUDY DESIGN AND SETTING: Repeatability/validity study conducted among
      114 participants randomly selected from the cohort to complete the survey
      instrument a second time and to undergo a physician skin examination. We
      calculated intraclass correlation coefficients (ICCs) and kappa (kappa)
      statistics as measures of agreement for continuous and categorical measures,
      respectively. RESULTS: Measures of phenotypic characteristics showed moderate-to
      high agreement (e.g., eye color, kappa=0.87; 95% confidence interval [CI]: 0.80,
      0.94). Measures of sun exposure had slightly lower estimates of agreement. The
      repeatability of items relating to medical and family history of skin cancer was
      high (e.g., the number of skin cancers removed surgically, kappa(w)=0.79; 95% CI:
      0.71, 0.88). Physician counts of nevi correlated well with categorical measures
      of self-reported nevus density at the age of 21 years but correlated only
      modestly with absolute nevus counts conducted by participants (ICC, 0.38; 95% CI:
      0.19, 0.54). CONCLUSION: Our survey instrument demonstrated fair-to-good test
      retest reliability for most self-reported risk factors for melanoma, indicating
      the suitability of these items for developing risk prediction tools in the
      future.

PMID- 22974497
TI  - The updated clinical guideline development process in Estonia is an efficient
      method for developing evidence-based guidelines.
AB  - Clinical practice guidelines are one of the tools available to improve the
      quality of health care. However, it may be difficult for countries to develop
      their own national guidelines "from scratch" because of limitations in time,
      expertise, and financial resources. The Estonian Health Insurance Fund (EHIF), in
      collaboration with other stakeholders, has launched a national effort to develop
      and implement evidence-based clinical practice guidelines aimed at improving the
      quality of care. Although the first EHIF handbook for preparing guidelines was
      published in 2004, there has been wide variation in the format and quality of
      guidelines prepared by medical specialty societies, EHIF, and other organizations
      in Estonia. An additional challenge to guideline development in Estonia is that
      it is a country with limited human resources. Therefore, revision of the Estonian
      guideline process was aimed at developing an efficient method for adapting
      current high-quality guidelines to the Estonian setting without compromising
      their quality. In 2010, a comprehensive assessment of guideline development in
      Estonia was made by the World Health Organization, EHIF, the Medical Faculty at
      the University of Tartu, and selected national and international experts in an
      effort to streamline and harmonize the principles and processes of guideline
      development in Estonia. This study summarizes the evaluation of and revisions to
      the process. Estonia has made substantial changes in its processes of clinical
      practice guideline development and implementation as part of an overall program
      aiming for systematic quality improvement in health care. This experience may be
      relevant to other small or resource-limited countries.

PMID- 22974498
TI  - Interpretability of change in the Nurses Work Functioning Questionnaire: minimal
      important change and smallest detectable change.
AB  - OBJECTIVES: The present study evaluates the interpretability of individual
      changes and assesses the minimal important change (MIC) for improvement and the
      smallest detectable change (SDC) of the Nurses Work Functioning Questionnaire
      (NWFQ). STUDY DESIGN AND SETTING: Data of two time points, baseline and 3-month
      follow-up, of a randomized controlled trial were used. A total of 358 nurses and
      allied health professionals of one Dutch academic medical center participated at
      both measurement points. Separate MIC values were calculated for the total score
      of the NWFQ and its six subscales, using two anchor-based methods: mean change
      and receiver operating characteristics (ROC) curve methods. Two methods for
      baseline corrections were applied: subgroup analyses and MIC calculation based on
      relative change scores. The SDCs were calculated using the standard error of the
      measurement. RESULTS: MIC values ranged from 3.4 to 8.3 for the mean change
      method and from 1.5 to 9.5 for the ROC curve method. In a subgroup with high
      baseline scores, the MIC values of the two methods ranged from 4.4 to 29 and 9.5
      to 41.5, respectively. The SDC values ranged from 7.2 to 17. Only one MIC value
      exceeded the SDC; however, 10 of the 14 MIC values exceeded the SDC in the high
      baseline group. CONCLUSION: Three of the seven NWFQ scales exhibited sufficient
      interpretability of individual change. For four scales, conclusions on the
      interpretability of change cannot yet be drawn. SDCs were small compared with the
      scale range.

PMID- 22974499
TI  - Maternal perinatal depression is not independently associated with child body
      mass index in the Generation R Study: methods and missing data matter.
AB  - OBJECTIVES: To advance the understanding of the relationship between maternal
      perinatal depression and child overweight, we used appropriate methodology to
      account for missing data; incorporated three exposure time points; and included
      adequate covariate adjustment in a large, sociodemographically diverse sample.
      STUDY DESIGN AND SETTING: We used data from 6,782 mother-child pairs in a
      prospective population-based study. Maternal depression was assessed with the
      Brief Symptom Inventory at midpregnancy and 2 and 6 months postpartum. Child
      height and weight were measured at 36 months of age and converted to body mass
      index (BMI) z-scores. We compared the complete-case and multiple imputation (MI)
      analyses. RESULTS: Fully adjusted complete-case models showed a positive
      association between depression at 2 months postpartum and child BMI z-score
      (beta=0.19 [95% confidence interval (CI)=0.03, 0.36]; n=1,732), and no
      association between prenatal depression or 6-month postpartum depression and
      child BMI. Using MI (n=6,782), there was no association between perinatal
      depression and child BMI at any time point. CONCLUSIONS: Our study adds evidence
      that postpartum depression is not associated with child growth across the
      population in high-income countries. Our results highlight the importance of
      appropriate handling of missing data, adequate covariate control, and the value
      of studying the conditions that have produced conflicting evidence regarding
      perinatal depression and child weight.

PMID- 22974500
TI  - Silent brain infarction in patients presenting with mechanical heart valve
      thrombosis.

PMID- 22974501
TI  - Insights into the impact and use of research results in a residential long-term
      care facility: a case study.
AB  - BACKGROUND: Engaging end-users of research in the process of disseminating
      findings may increase the relevance of findings and their impact for users. We
      report findings from a case study that explored how involvement with the
      Translating Research in Elder Care (TREC) study influenced management and staff
      at one of 36 TREC facilities. We conducted the study at 'Restwood' (pseudonym)
      nursing home because the Director of Care engaged actively in the study and TREC
      data showed that this site differed on some areas from other nursing homes in the
      province. The aims of the case study were two-fold: to gain a better
      understanding of how frontline staff engage with the research process, and to
      gain a better understanding of how to share more detailed research results with
      management. METHODS: We developed an Expanded Feedback Report for use during this
      study. In it, we presented survey results that compared Restwood to the best
      performing site on all variables and participating sites in the province. Data
      were collected regarding the Expanded Feedback Report through interviews with
      management. Data from staff were collected through interviews and observation. We
      used content analysis to derive themes to describe key aspects related to the
      study aims. RESULTS: We observed the importance of understanding organizational
      routines and the impact of key events in the facility's environment. We gleaned
      additional information that validated findings from prior feedback mechanisms
      within TREC. Another predominant theme was the sense that the opportunity to
      engage in a research process was reaffirming for staff (particularly healthcare
      aides)-what they did and said mattered, and TREC provided a means of having one's
      voice heard. We gained valuable insight from the Director of Care about how to
      structure and format more detailed findings to assist with interpretation and use
      of results. CONCLUSIONS: Four themes emerged regarding staff engagement with the
      research process: sharing feedback reports from the TREC study; the meaning of
      TREC to staff; understanding organizational context; and using the study feedback
      for improvement at Restwood. This study has lessons for researchers on how to
      share research results with study participants, including management.

PMID- 22974502
TI  - A proteomics approach to investigate the process of Zn hyperaccumulation in
      Noccaea caerulescens (J & C. Presl) F.K. Meyer.
AB  - Zinc (Zn) is an essential trace element in all living organisms, but is toxic in
      excess. Several plant species are able to accumulate Zn at extraordinarily high
      concentrations in the leaf epidermis without showing any toxicity symptoms.
      However, the molecular mechanisms of this phenomenon are still poorly understood.
      A state-of-the-art quantitative 2D liquid chromatography/tandem mass spectrometry
      (2D-LC-MS/MS) proteomics approach was used to investigate the abundance of
      proteins involved in Zn hyperaccumulation in leaf epidermal and mesophyll tissues
      of Noccaea caerulescens. Furthermore, the Zn speciation in planta was analyzed by
      a size-exclusion chromatography/inductively coupled plasma mass spectrometer (SEC
      ICP-MS) method, in order to identify the Zn-binding ligands and mechanisms
      responsible for Zn hyperaccumulation. Epidermal cells have an increased
      capability to cope with the oxidative stress that results from excess Zn, as
      indicated by a higher abundance of glutathione S-transferase proteins. A Zn
      importer of the ZIP family was more abundant in the epidermal tissue than in the
      mesophyll tissue, but the vacuolar Zn transporter MTP1 was equally distributed.
      Almost all of the Zn located in the mesophyll was stored as Zn-nicotianamine
      complexes. In contrast, a much lower proportion of the Zn was found as Zn
      nicotianamine complexes in the epidermis. However, these cells have higher
      concentrations of malate and citrate, and these organic acids are probably
      responsible for complexation of most epidermal Zn. Here we provide evidence for a
      cell type-specific adaptation to excess Zn conditions and an increased ability to
      transport Zn into the epidermal vacuoles. 

PMID- 22974503
TI  - Investigation of auditory processing disorder and language impairment using the
      speech-evoked auditory brainstem response.
AB  - This study investigated whether there are differences in the Speech-Evoked
      Auditory Brainstem Response among children with Typical Development (TD),
      (Central) Auditory Processing Disorder (C)APD, and Language Impairment (LI). The
      speech-evoked Auditory Brainstem Response was tested in 57 children (ages 6-12).
      The children were placed into three groups: TD (n = 18), (C)APD (n = 18) and LI
      (n = 21). Speech-evoked ABR were elicited using the five-formant syllable/da/.
      Three dimensions were defined for analysis, including timing, harmonics, and
      pitch. A comparative analysis of the responses between the typical development
      children and children with (C)APD and LI revealed abnormal encoding of the speech
      acoustic features that are characteristics of speech perception in children with
      (C)APD and LI, although the two groups differed in their abnormalities. While the
      children with (C)APD might had a greater difficulty distinguishing stimuli based
      on timing cues, the children with LI had the additional difficulty of
      distinguishing speech harmonics, which are important to the identification of
      speech sounds. These data suggested that an inefficient representation of crucial
      components of speech sounds may contribute to the difficulties with language
      processing found in children with LI. Furthermore, these findings may indicate
      that the neural processes mediated by the auditory brainstem differ among
      children with auditory processing and speech-language disorders.

PMID- 22974504
TI  - Time dependence of reliability of noncontrast computed tomography in comparison
      to computed tomography angiography source image in acute ischemic stroke.
AB  - There is no consensus on how the reliability and predictive ability of
      noncontrast computed tomography (NCCT) and computed tomography angiography source
      image (CTASI) change over time from acute ischemic stroke onset. We hypothesized
      that the reliability for detecting early ischemic changes (EIC) would be lower in
      early time periods and that changes identified on CTASI would be more reliable
      across examiners than changes identified on NCCT. To address this, we compared
      the relationships between CTASI, NCCT, and final infarct in patients with initial
      computed tomography (CT) imaging at different time points after stroke onset.
      Patients with acute ischemic stroke with proximal anterior circulation occlusions
      (internal carotid artery, middle carotid artery M1, proximal M2) from Calgary CT
      Angiography (CTA) database were studied. The cohort was categorized in four
      groups based on time from stroke onset to baseline NCCT/CTA: 0-90 mins (n = 69),
      91-180 mins (n = 88), 181-360 mins (n = 46), and >360 mins (n = 58). Median
      scores of NCCT-Alberta Stroke Program Early CT Score (ASPECTS), CTASI ASPECTS,
      and follow-up ASPECTS among different time categories were compared. To determine
      reliability, a subsample of NCCT brain and CTASI were interpreted at separate
      sessions weeks apart by two neuroradiologists and two stroke neurologists in
      random order. Median and mean ASPECTS ratings on NCCT and CTASI were higher than
      final ASPECTS in each time category (P < 0.001 for all comparisons). CTASI
      ASPECTS was lower than NCCT ASPECTS in each time category, and differences were
      significant at 0-90 mins and 91-180 mins (P < 0.001). The least agreement among
      readers was in detection of EIC on NCCT brain in the ultra-early phase (<90 mins)
      [intraclass correlation coefficient (ICC) = 0.48. By contrast, there was
      excellent agreement on EIC on CTASI regardless of time period (ICC = 0.87-0.96).
      Using ASPECTS methodology, CTASI is more reliable than NCCT at predicting final
      infarct extent particularly in the early time windows. 

PMID- 22974505
TI  - Fusogenic metallosupramolecular brush vesicles.
AB  - The electrostatic combination of a cationic metallosupramolecular polyelectrolyte
      (Fe-MSP) with sulfonate-terminated polymers leads to the formation of
      metallosupramolecular brushes (MSBs). The resulting MSBs can self-assemble into
      vesicular structures in chloroform/methanol (v/v = 1:1) mixture solvents. The
      rigid-rod Fe-MSP chain has to bend for the formation of the vesicles, which
      accompanies the presence of a lateral tension and thus induces a spontaneous
      vesicle fusion with an hour-scale fusion time. For this much longer fusion
      process, the arrow-like protrusion, stalk-like intermediate, and hemifusion
      diaphragm are clearly observed by transmission electron microscopy. The complete
      fusion into larger vesicles significantly releases the lateral tension.

PMID- 22974506
TI  - Satellite-based studies on large-scale vegetation changes in China.
AB  - Remotely-sensed vegetation indices, which indicate the density and photosynthetic
      capacity of vegetation, have been widely used to monitor vegetation dynamics over
      broad areas. In this paper, we reviewed satellite-based studies on vegetation
      cover changes, biomass and productivity variations, phenological dynamics,
      desertification, and grassland degradation in China that occurred over the past 2
      3 decades. Our review shows that the satellite-derived index (Normalized
      Difference Vegetation Index, NDVI) during growing season and the vegetation net
      primary productivity in major terrestrial ecosystems (for example forests,
      grasslands, shrubs, and croplands) have significantly increased, while the number
      of fresh lakes and vegetation coverage in urban regions have experienced a
      substantial decline. The start of the growing season continually advanced in
      China's temperate regions until the 1990s, with a large spatial heterogeneity. We
      also found that the coverage of sparsely-vegetated areas declined, and the NDVI
      per unit in vegetated areas increased in arid and semi-arid regions because of
      increased vegetation activity in grassland and oasis areas. However, these
      results depend strongly not only on the periods chosen for investigation, but
      also on factors such as data sources, changes in detection methods, and
      geospatial heterogeneity. Therefore, we should be cautious when applying remote
      sensing techniques to monitor vegetation structures, functions, and changes.

PMID- 22974507
TI  - Streptococcus gordonii septic arthritis: two cases and review of literature.
AB  - BACKGROUND: Despite advances in antimicrobial and surgical therapy, septic
      arthritis remains a rheumatologic emergency that can lead to rapid joint
      destruction and irreversible loss of function. In adults, Staphylococcus aureus
      is the most common microorganism isolated from native joints. Streptococcus
      gordonii is a prominent member of the viridans group of oral bacteria and is
      among the bacteria most frequently identified as being primary agent of subacute
      bacterial endocarditis. To the best of our knowledge, Streptococcus gordonii has
      not yet been described as agent of septic arthritis. CASE PRESENTATION: We
      describe here two cases of septic arthritis due to Streptococcus gordonii. It
      gives us an opportunity to review epidemiology, diagnosis criteria and management
      of septic arthritis. CONCLUSION: Although implication of S. gordonii as
      aetiologic agent of subacute endocarditis is well known, this organism is a rare
      cause of septic arthritis. In this case, the exclusion of associated endocarditis
      is warranted.

PMID- 22974508
TI  - Evidence for nutrition transition in Kuwait: over-consumption of macronutrients
      and obesity.
AB  - OBJECTIVES: To describe nutrient intakes and prevalence of overweight and obesity
      in a nationally representative sample of Kuwaitis and to compare intakes with
      reference values. DESIGN: Cross-sectional, multistage stratified, cluster sample.
      Settings National nutrition survey covering all geographical areas of the
      country. SUBJECTS: Kuwaitis (n 1704) between 3 and 86 years of age. RESULTS:
      Obesity was more prevalent among women than men (50 % and 70 % for females aged
      19-50 years and >=51 years, respectively, v. 29 % and 42 % for their male
      counterparts). Boys were more obese than girls, with the highest obesity rate
      among those aged 9-13 years (37 % and 24 % of males and females, respectively).
      Energy intake was higher than the estimated energy requirements for almost half
      of Kuwaiti children and one-third of adults. The Estimated Average Requirement
      was exceeded by 78-100 % of the recommendation for protein and carbohydrates.
      More than two-thirds of males aged >=4 years exceeded the Tolerable Upper Intake
      Level for Na. Conversely, less than 20 % of Kuwaitis, regardless of age, consumed
      100 % or more of the Estimated Average Requirement for vitamin D, vitamin E, Ca,
      n-3 and n-6 fatty acids. Less than 20 % of children met the recommended level for
      fibre. CONCLUSIONS: Nutrition transition among Kuwaitis was demonstrated by the
      increased prevalence of obesity and overweight, increased intakes of energy and
      macronutrients and decreased intakes of fibre and micronutrients. Interventions
      to increase awareness about healthy foods combined with modifications in subsidy
      policies are clearly warranted to increase consumption of low-energy, nutrient
      dense foods.

PMID- 22974509
TI  - Arabidopsis RABA1 GTPases are involved in transport between the trans-Golgi
      network and the plasma membrane, and are required for salinity stress tolerance.
AB  - RAB GTPases are key regulators of membrane traffic. Among them, RAB11, a widely
      conserved sub-group, has evolved in a unique way in plants; plant RAB11 members
      show notable diversity, whereas yeast and animals have only a few RAB11 members.
      Fifty-seven RAB GTPases are encoded in the Arabidopsis thaliana genome, 26 of
      which are classified in the RAB11 group (further divided into RABA1-RABA6 sub
      groups). Although several plant RAB11 members have been shown to play pivotal
      roles in plant-unique developmental processes, including cytokinesis and tip
      growth, molecular and physiological functions of the majority of RAB11 members
      remain unknown. To reveal precise functions of plant RAB11, we investigated the
      subcellular localization and dynamics of the largest sub-group of Arabidopsis
      RAB11, RABA1, which has nine members. RABA1 members reside on mobile punctate
      structures adjacent to the trans-Golgi network and co-localized with VAMP721/722,
      R-SNARE proteins that operate in the secretory pathway. In addition, the
      constitutive-active mutant of RABA1b, RABA1b(Q72L) , was present on the plasma
      membrane. The RABA1b -containing membrane structures showed actin-dependent
      dynamic motion . Vesicles labeled by GFP-RABA1b moved dynamically, forming queues
      along actin filaments. Interestingly, Arabidopsis plants whose four major RABA1
      members were knocked out, and those expressing the dominant-negative mutant of
      RABA1B, exhibited hypersensitivity to salinity stress. Altogether, these results
      indicate that RABA1 members mediate transport between the trans-Golgi network and
      the plasma membrane, and are required for salinity stress tolerance.

PMID- 22974510
TI  - Sexual bipotentiality of behavior in male and female goldfish.
AB  - It is known that in goldfish Carassius auratus, a non-sex changing fish,
      prostaglandin (PG) treatment can induce female-typical sex behavior in males, and
      androgen treatment can induce male-typical sex behavior in females. These facts
      suggest that goldfish have a sexually bipotential brain even after attaining
      sexual maturity unlike mammals which have sexually differentiated brain. In the
      present study, in order to further characterize the brain function of goldfish,
      whether hormonal treatments which induce heterotypical sexual behavior suppress
      the occurrence of sex-typical behavior and whether sex-typical and heterotypical
      behavior can be induced in a relatively short time were examined. In the first
      series of experiments, male goldfish were shown to retain their ability to
      perform male-typical sex behavior within a week after being induced to perform
      female-typical behavior. Likewise, female goldfish were also shown to retain
      their female-typical sex behavior a week after being induced to perform male
      typical behavior. In the second series of experiments, when PG-injected
      experimental males were placed with both PG-injected females and sexually mature
      males, the experimental males performed male- and female-typical behavior
      alternately with the females and the males, respectively during 90 min test
      period. When methyltestosterone-treated experimental females were injected with
      PG and placed with both PG-injected females and mature males, the experimental
      females performed male- and female-typical behavior alternately during 90 min
      test period. The results of the present study are consistent with the current
      knowledge that goldfish possess a sexually bipotential brain that can regulate
      both male and female-typical sex behaviors.

PMID- 22974511
TI  - A review on the effect of the photoperiod and melatonin on interactions between
      ghrelin and serotonin.
AB  - Ghrelin and serotonin, which exhibit rhythmic secretion profiles under
      feeding/fasting conditions, are sensitive to increases and decreases in the day
      length and form a close web of interrelationships in the regulation of energy
      homeostasis. Ghrelin and serotonin are biochemically and functionally linked to
      the suprachiasmatic nucleus, which is a circadian pacemaker, and melatonin, which
      is an internal transducer of photic environmental changes. Ghrelin and serotonin
      might be candidates for integrating photic and nonphotic signals, such as light
      and food availability in the central nervous system. The mechanisms that convert
      a light signal into a variety of physiological and behavioral rhythms remain
      unknown. However, we know that the conversion of light signals is necessary to
      maximize an animal's chances of survival and reproduction.

PMID- 22974512
TI  - Exploring the cyclooxygenase 2 (COX2)/15d-Delta(12,14)PGJ(2) system in hamster
      Sertoli cells: regulation by FSH/testosterone and relevance to glucose uptake.
AB  - We have previously described a stimulatory effect of testosterone on
      cyclooxygenase 2 (COX2) expression and prostaglandin (PG) synthesis, and the
      involvement of PGs in the modulation of testosterone production in Leydig cells
      of the seasonal breeder Syrian hamster. In this study, we investigated the
      existence of a COX2/PGs system in hamster Sertoli cells, its regulation by
      testosterone and FSH, and its effect on glucose uptake. COX2 expression was
      observed in Sertoli cells of both reproductively active and inactive adult
      hamsters. Testosterone and the plasma membrane-impermeable testosterone-BSA
      significantly induced COX2 expression, mitogen activated protein kinases 1/2
      (MAPK1/2) phosphorylation and 15d-Delta(12,14)PGJ(2) production in Sertoli cells
      purified from photoperiodically regressed hamsters. These actions were abolished
      by the antiandrogen bicalutamide and by the inhibitor of MAPK kinase (MEK1/2)
      U0126, suggesting that testosterone exerts its stimulatory effect on COX2/PGs
      through a non-classical mechanism that involves the presence of androgen
      receptors and MAPK1/2 activation. FSH also stimulated COX2/PGs via MAPK1/2
      phosphorylation. FSH and testosterone stimulate, whereas 15d-Delta(12,14)PGJ(2)
      via PPARgamma inhibits, [2,6-(3)H]-2-deoxy-d-glucose ([(3)H]-2-DOG) uptake.
      Meloxicam, a selective COX2 inhibitor, further increases [(3)H]-2-DOG uptake in
      the presence of FSH or testosterone. Thus, in addition to their positive effect,
      FSH and testosterone may also exert an indirect negative regulation on glucose
      uptake which involves the COX2/15d-Delta(12,14)PGJ(2)/PPARgamma system. Overall,
      these results demonstrate the presence of a COX2/PG system in hamster Sertoli
      cells which might act as a local modulator of FSH and testosterone actions.

PMID- 22974513
TI  - The influence of reproductive hormones on the torpor patterns of the marsupial
      Sminthopsis macroura: bet-hedging in an unpredictable environment.
AB  - Seasonal cycles of reproduction are common in many mammals and these are combined
      with the necessary energy budgeting for thermoregulatory challenges. Many mammals
      meet the challenge of changing environmental temperatures in winter by using
      torpor, a controlled reduction in body temperature and metabolic rate. We aimed
      to determine the effects of photoperiod and reproductive hormones on the seasonal
      cycles of reproduction and torpor use in a marsupial that commences reproduction
      in winter, the stripe-faced dunnart, Sminthopsis macroura. Males and females were
      placed under LD 14:10 and natural reproductive hormones blocked by either
      flutamide (males) or mifepristone (females) or tamoxifen (females). Reproductive
      parameters, metabolic rate and torpor variables were determined. The same animals
      were then placed under LD 10:14 and given testosterone (males) or progesterone
      (females) or oestrogen (females). Reproductive parameters, metabolic rate and
      torpor variables were measured. Body mass and tail widths (fattening indicator)
      in males were significantly affected by testosterone, and the effects were
      reversed by hormone blockers. Reproductive parameters were unaffected. Resting
      metabolic rate and ability to use torpor were not affected by treatment in males,
      however torpor characteristics, especially torpor bout duration, were affected by
      presence of testosterone in males. In females, body mass was unaffected by
      hormone presence, although tail widths were affected. Disruption of reproductive
      cycles occurred with hormone blockers in females, however, resting metabolic rate
      was not affected, and only presence of progesterone affected torpor
      characteristics in females. Our results differ from those found for rodents,
      where presence of testosterone abolishes the use of torpor in males, and
      oestrogen inhibits torpor use in females. Our study suggests that, in this
      mammal, metabolic responses to the presence or absence of reproductive hormones
      differs between males and females, and there is no absolute endocrinologically
      driven reproductive season demarcated from the torpor season.

PMID- 22974514
TI  - How to improve communication for the safe use of medicines?: Discussions on
      social marketing and patient-tailored approaches at the annual meetings of the
      WHO Programme for International Drug Monitoring.
AB  - Over the past decade, the annual meetings of national centres participating in
      the WHO Programme for International Drug Monitoring have increasingly included
      discussions on how to improve communication between national pharmacovigilance
      centres, patients, healthcare professionals, policy makers and the general
      public, with the aim of promoting the safe use of medicines. At the most recent
      meetings, working groups were dedicated to discuss possible applications and
      implementation of social marketing and patient-tailored approaches. This article
      provides the history and a summary of the recent discussions and recommendations
      to support progress in this respect at national and global level. Recommendations
      are made to investigate and pilot these approaches in small-scale projects at
      national pharmacovigilance centres. Applying elements from the social marketing
      and patient-tailored approaches to support behaviours of safe medicines use in
      patients and healthcare professionals should give the pharmacovigilance community
      new tools to achieve their goal to minimize risks with medicines and improve
      patient safety.

PMID- 22974515
TI  - Radiation dose >=54 Gy and CA 19-9 response are associated with improved survival
      for unresectable, non-metastatic pancreatic cancer treated with chemoradiation.
AB  - BACKGROUND: Unresectable pancreatic cancer (UPC) has low survival. With improving
      staging techniques and systemic therapy, local control in patients without
      metastatic disease may have increasing importance. We investigated whether the
      radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and
      the CA 19-9 response to therapy have an impact on overall survival (OS). METHODS:
      From 1997-2009 46 patients were treated with CRT for non-metastatic UPC. Median
      prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received
      concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant
      chemotherapy. RESULTS: 41 patients were inoperable due to T4 disease and 5
      patients with T3 disease were medically inoperable. Five patients did not
      complete CRT due to progressive disease or treatment-related toxicity (median RT
      dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last
      follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By
      univariate analysis, minimum CA 19-9 post-CRT <90 U/mL was favorably associated
      with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose >=54 Gy trended
      towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable
      analysis, a delivered RT dose of >=54 Gy (HR 0.47, p = 0.028) and minimum CA 19-9
      post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS. CONCLUSIONS:
      CRT as definitive treatment for UPC had low survival. However, our retrospective
      data suggest that patients treated to >=54 Gy or observed to have a minimum post
      CRT CA 19-9 <90 U/mL had improved likelihood of long-term survival.

PMID- 22974516
TI  - Inpatient stroke care quality for veterans: are there differences between
      Veterans Affairs medical centers in the stroke belt and other areas?
AB  - BACKGROUND: Stroke mortality has been found to be much higher among residents in
      the stroke belt region than in the rest of United States, but it is not known
      whether differences exist in the quality of stroke care provided in Department of
      Veterans Affairs medical centers in states inside and outside this region.
      OBJECTIVE: We compared mortality and inpatient stroke care quality between
      Veterans Affairs medical centers inside and outside the stroke belt region.
      METHODS: Study patients were veterans hospitalized for ischemic stroke at 129
      Veterans Affairs medical centers. Inpatient stroke care quality was assessed by
      14 quality indicators. Multivariable logistic regression models were fit to
      examine differences in quality between facilities inside and outside the stroke
      belt, adjusting for patient characteristics and Veterans Affairs medical centers
      clustering effect. RESULTS: Among the 3909 patients, 28.1% received inpatient
      ischemic stroke care in 28 stroke belt Veterans Affairs medical centers, and
      71.9% obtained care in 101 non-stroke belt Veterans Affairs medical centers.
      Patients cared for in stroke belt Veterans Affairs medical centers were more
      likely to be younger, Black, married, have a higher stroke severity, and less
      likely to be ambulatory pre-stroke. We found no statistically significant
      differences in short- and long-term post-admission mortality and inpatient care
      quality indicators between the patients cared for in stroke belt and non-stroke
      belt Veterans Affairs medical centers after risk adjustment. CONCLUSIONS: These
      data suggest that a stroke belt does not exist within the Veterans Affairs health
      care system in terms of either post-admission mortality or inpatient care
      quality.

PMID- 22974517
TI  - Direct, rapid, facile photochemical method for preparing copper nanoparticles and
      copper patterns.
AB  - We develop a facile method for preparing copper nanoparticles and patterned
      surfaces with copper stripes by ultraviolet (UV) irradiation of a mixture
      solution containing a photoinitiator and a copper-amine coordination compound.
      The copper-amine compound is formed by adding diethanol amine to an ethanol
      solution of copper chloride. Under UV irradiation, free radicals are generated by
      photoinitiator decomposition. Meanwhile, the copper-amine coordination compound
      is rapidly reduced to copper particles because the formation of the copper-amine
      coordination compound prevents the production of insoluble cuprous chloride.
      Poly(vinylpyrrolidone) is used as a capping agent to prevent the aggregation of
      the as-prepared copper nanoparticles. The capping agent increases the dispersion
      of copper nanoparticles in the ethanol solution and affects their size and
      morphology. Increasing the concentration of the copper-amine coordination
      compound to 0.1 M directly forms a patterned surface with copper stripes on the
      transparent substrate. This patterned surface is formed through the combination
      of the heterogeneous nucleation of copper nanoparticles and photolithography. We
      also investigate the mechanism of photoreduction by UV-vis spectroscopy and gas
      chromatography-mass spectrometry.

PMID- 22974518
TI  - Predictors of post-partum weight retention in a prospective longitudinal study.
AB  - Post-partum weight retention (WR) occurs in 60-80% of women with some retaining
      >=10 kg with contributing factors reported as pre-pregnancy body mass index
      (BMI), gestational weight gain (GWG) and breastfeeding. A longitudinal study of
      pregnancy, with 12-month post-partum follow-up was conducted to determine factors
      associated with WR. Pregnant women (n = 152) were recruited from the John Hunter
      Hospital antenatal clinic in New South Wales, Australia. Pre-pregnancy weight was
      self-reported; weight was measured four times during pregnancy (for GWG) and in
      the first 12 months post-partum. Infant feeding data were obtained via
      questionnaires. Breastfeeding was categorised as exclusive, predominant,
      complementary or not breastfeeding. Linear mixed models tested the predictors of
      WR, with and without adjustment for potential confounders. Compared with pre
      pregnancy weight, 68% of women retained weight at 12 months, median
      (interquartile range) [4.5 kg (2.1-8.9)]. After adjustment, GWG was positively
      associated with WR (P < 0.01), but pre-pregnancy weight did not predict WR. For
      each additional week of any breastfeeding, 0.04 kg less weight was retained.
      Compared with women who retained weight, those women who did retain had higher
      rates of exclusive breastfeeding at three months (P < 0.05), but the number of
      weeks of exclusive breastfeeding failed to predict WR for all women. WR following
      childbirth is common and associated with GWG, while the number of weeks of 'any'
      breastfeeding contributed to post-partum weight loss. Whether these factors are
      modifiable strategies to optimise the weight status of women at this life stage
      requires further research.

PMID- 22974519
TI  - Person-centered care and quality of life of patients with dementia in long-term
      care facilities.
AB  - Good quality of life (QOL) is an important goal of dementia care. However, there
      have been few studies on the relationship of care characteristics to QOL of
      dementia patients in long-term care facilities. We developed a questionnaire
      evaluating person-centered care and used it to assess person-centered care and
      QOL of elderly patients with dementia in both geriatric health service facilities
      (GHSF) and hospitals. In GHSF, person-centered care scores were not correlated
      with cognitive or activities of daily living (ADL) functions, but were
      significantly correlated with four subscale scores on a quality of life
      questionnaire for dementia (QOL-D) after controlling the effect of age, cognitive
      function, and ADL scores. In contrast, in hospitals, person-centered care scores
      were significantly correlated with cognitive and ADL function. We found quite
      different patterns in the relationship of person-centered care scores to clinical
      characteristics. Dementia care characteristics and QOL of dementia patients are
      significantly interrelated, especially in GHSF. Improvement of dementia care
      standards might affect the QOL of dementia patients. We should pay more attention
      to the quality of dementia care and QOL of dementia patients.

PMID- 22974520
TI  - Negative symptom measurement in individuals at-risk for psychosis.

PMID- 22974521
TI  - Subscale structure for the Positive and Negative Syndrome Scale (PANSS): a
      proposed solution focused on clinical validity.
AB  - Although the items of the Positive and Negative Syndrome Scale (PANSS) are
      ordinal, continuous data methods are consistently used to analyze them. The
      current study addresses this issue by applying a categorical method and
      critically examining the ideas of item inclusion and goodness of fit. Data from
      1527 subjects were used to test a proposed solution to the factor structure of
      the PANSS using a categorical factor analytic method. The model was made more
      generalizable by setting a minimum level of association between the item and the
      factor, and the results were then compared to existing solutions. The model was
      also tested for consistency in a first-episode sample. Use of categorical methods
      indicated similar results to previous analyses; however, it is demonstrated that
      the strength of the estimates can be unstable when items are shared across
      factors. The current study demonstrates that solutions can change substantially
      when a model is over-fitted, and therefore use of measures of fit as the
      criterion for an acceptable model can mask important relationships and decrease
      clinical validity.

PMID- 22974522
TI  - Replication factor C1 (RFC1) is required for double-strand break repair during
      meiotic homologous recombination in Arabidopsis.
AB  - Replication factor C1 (RFC1), which is conserved in eukaryotes, is involved in
      DNA replication and checkpoint control. However, a RFC1 product participating in
      DNA repair at meiosis has not been reported in Arabidopsis. Here, we report
      functional characterization of AtRFC1 through analysis of the rfc1-2 mutant. The
      rfc1-2 mutant displayed normal vegetative growth but showed silique sterility
      because the male gametophyte was arrested at the uninucleus microspore stage and
      the female at the functional megaspore stage. Expression of AtRFC1 was
      concentrated in the reproductive organ primordia, meiocytes and developing
      gametes. Chromosome spreads showed that pairing and synapsis were normal, and the
      chromosomes were broken when desynapsis began at late prophase I, and chromosome
      fragments remained in the subsequent stages. For this reason, homologous
      chromosomes and sister chromatids segregated unequally, leading to pollen
      sterility. Immunolocalization revealed that the AtRFC1 protein localized to the
      chromosomes during zygotene and pachytene in wild-type but were absent in the
      spo11-1 mutant. The chromosome fragmentation of rfc1-2 was suppressed by spo11-1,
      indicating that AtRFC1 acted downstream of AtSPO11-1. The similar chromosome
      behavior of rad51 rfc1-2 and rad51 suggests that AtRFC1 may act with AtRAD51 in
      the same pathway. In summary, AtRFC1 is required for DNA double-strand break
      repair during meiotic homologous recombination of Arabidopsis. 

PMID- 22974523
TI  - Dietary patterns throughout childhood and associations with nutrient intakes.
AB  - OBJECTIVE: To examine how the dietary patterns of children at various time points
      throughout childhood relate to estimated nutrient intakes. DESIGN: FFQ at 3, 4, 7
      and 9 years of age were completed by mothers. Dietary patterns were identified
      cross-sectionally using principal component analysis; 'processed', 'health
      conscious' and 'traditional' patterns were consistently obtained. Correlations
      between pattern scores and nutrient intakes and proportions of variance in
      nutrients explained by the patterns were calculated. SETTING: Avon Longitudinal
      Study of Parents and Children (ALSPAC), Bristol, UK. SUBJECTS: Children provided
      data between 3 and 9 years of age (n 8010 to 10,023). RESULTS: Dietary patterns
      explained substantial proportions of the variance of the absolute intake for most
      nutrients (>25% at 3 years of age, >40% other ages). After energy adjustment,
      protein, fibre, K, Mg, Fe, Zn, folate, thiamin and vitamin B6 continued to be
      well explained. Strong correlations were observed between the 'processed' pattern
      and macronutrients including energy (r=0.481-0.619), total fat (r=0.529-0.662)
      and total sugar (r=0.475-0.693). However correlations with most micronutrients
      were reversed after energy adjustment, suggesting that the 'processed' pattern is
      energy-dense but nutrient-poor. The 'health conscious' and 'traditional' patterns
      were strongly positively correlated with protein, fibre and most micronutrients,
      whether energy adjusted or not. Higher scores on these patterns were associated
      with a better nutrient profile. CONCLUSIONS: Dietary patterns explain a
      reasonable amount of the variation in the nutrient content of diets. Higher
      scores on the 'health conscious' and 'traditional' dietary patterns were related
      to better nutrient profiles; conversely, with higher scores on the 'processed'
      pattern the nutrient profile was poorer.

PMID- 22974524
TI  - Pigment epithelium-derived factor gene loaded in cRGD-PEG-PEI suppresses
      colorectal cancer growth by targeting endothelial cells.
AB  - Pigment epithelium-derived factor (PEDF) recombinant protein has been
      investigated in many kinds of solid tumors due to its potent antiangiogenic
      activity. However, the complexity of protein purification, instability of
      recombinant protein and requirement of repeated injections are obstacles for the
      recombinant PEDF therapy for solid tumors. We successfully synthesized
      polyethyleneglycol-polyetherimide (PEG-PEI) and cRGD-PEG-PEI which was coupled
      with a cyclic RGD peptide, a special ligand for integrin alphavbeta3 receptor, as
      the vehicle for PEDF gene therapy in this study. In vitro, the competitive
      binding assay showed that cRGD contributed to the enhanced gene transfection
      efficiency of PEG-PEI in human umbilical vein endothelial cells (HUVECs). PEDF
      gene delivered by cRGD-PEG-PEI apparently suppressed growth of tumor with a 67.4%
      reduction and decreased microvessel density in nude mice bearing SW620 human
      colorectal xenografts. Accordingly, SW620 tumors from cRGD-PEG-PEI/PEDF-pcDNA3.1
      (+)-treated mice expressed more PEDF than that of the control groups. Our study
      demonstrated that cRGD-PEG-PEI transported the PEDF gene into endothelia cells
      more efficiently than PEG-PEI, resulting in more effective inhibitory effects on
      tumor growth by anti-angiogenesis. Therefore, for the first time, we have
      explored an effective non-viral vehicle for PEDF gene therapy by targeting
      endothelial cells.

PMID- 22974525
TI  - Development of novel microprecipitated bulk powder (MBP) technology for
      manufacturing stable amorphous formulations of poorly soluble drugs.
AB  - A novel method was developed to manufacture amorphous formulations of poorly
      soluble compounds that cannot be processed with existing methods such as spray
      drying and melt extrusion. The manufacturing process and the characterization of
      the resulting amorphous dispersion are presented via examples of two research
      compounds. The novel process is utilized N,N-dimethylacetamide (DMA) to dissolve
      the drug and the selected ionic polymer. This solution is then co-precipitated
      into aqueous medium. The solvent is extracted out by washing and the co
      precipitated material is isolated by filtration followed by drying. The dried
      material is referred to as microprecipitated bulk powder (MBP). The amorphous
      form prepared using this method not only provides excellent in vitro and in vivo
      performance but also showed excellent stability. The stabilization of amorphous
      dispersion is attributed to the high T(g), ionic nature of the polymer that help
      to stabilize the amorphous form by possible ionic interactions, and/or due to the
      insolubility of polymer in water. In addition to being an alternate technology
      for amorphous formulation of difficult compounds, MBP technology provides
      advantages with respect to stability, density and downstream processing.

PMID- 22974526
TI  - Low-level detection and quantitation of cellular HIV-1 DNA and 2-LTR circles
      using droplet digital PCR.
AB  - Droplet digital PCR (ddPCR) is an emerging nucleic acid detection method that
      provides absolute quantitations of target sequences without relying on the use of
      standard curves. The ability of ddPCR to detect and quantitate total HIV-1 DNA
      and 2-LTR circles from a panel of patients on and off antiviral therapy was
      evaluated compared to established real-time (RT)-PCR methods. To calculate the
      dynamic range of ddPCR for HIV-1 DNA and 2-LTR circles, serial dilutions of DNA
      amplicons or episomes were determined by ddPCR as well as with RT-PCR. HIV-1 DNA
      from 3 viremic patients and 4 patients on suppressive antiretroviral therapy, and
      2-LTR circles from 3 patients with low-level viremia were also quantitated. Copy
      numbers determined by ddPCR of serial dilutions of HIV-1 or human CCR5 DNA
      amplicon standards were comparable to nominal input copy number. The sensitivity
      of ddPCR to detect HIV-1 or CCR5 DNA was similar to that of RT-PCR. Low levels of
      2-LTR circles were detected in samples from all 3 patients by both ddPCR and RT
      PCR. ddPCR is a promising novel technology for the study of HIV-1 reservoirs and
      persistence, but further optimization of this novel technology would enhance the
      detection of very low-level viral genetic targets.

PMID- 22974527
TI  - Etiology-specific differences in motor function after hemispherectomy.
AB  - Prediction of functional motor outcome after hemispherectomy is difficult due to
      the heterogeneity of motor outcomes observed. We hypothesize that this might be
      related to differences in plasticity during the onset of the underlying
      epileptogenic disorder or lesion and try to identify predictors of motor outcome
      after hemispherectomy. Thirty-five children with different etiologies
      (developmental, stable acquired or progressive) underwent functional
      hemispherectomy and motor function assessment before hemispherectomy and 24
      months after hemispherectomy. Preoperatively, children with developmental
      etiologies performed better in terms of distal arm strength and hand function,
      but not on gross motor function tests. Postoperatively, the three etiology groups
      performed equally poor in muscle strength and hand function, but gross motor
      function improved in those with acquired and progressive etiologies. Loss of
      voluntary hand function and distal arm strength after surgery was associated with
      etiology, intact insular cortex and intact structural integrity of the
      ipsilesional corticospinal tract on presurgical MRI scans. In conclusion,
      postoperative motor function can be predicted more precisely based on etiology
      and on preoperative MRI. Children with developmental etiology more often lose
      distal arm strength and hand function and show less improvement in gross motor
      function, compared to those with acquired pathology.

PMID- 22974528
TI  - EBP50 promotes focal adhesion turnover and vascular smooth muscle cells
      migration.
AB  - The ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a PDZ-containing
      scaffolding protein that regulates a variety of physiological functions. In the
      vasculature, EBP50 promotes neointima formation following arterial injury. In
      this study the role of EBP50 on vascular smooth muscle cell (VSMC) migration was
      characterized. The spreading and motility of primary VSMC isolated from EBP50
      knockout (KO) mice were significantly reduced compared to wild-type (WT) cells.
      EBP50-null VSMC had fewer and larger focal adhesions than wild-type cells.
      Assembly and disassembly of focal adhesion-assessed by live-cell total internal
      reflection fluorescence imaging-in response to epidermal growth factor (EGF) were
      significantly reduced in KO cells. Immunoprecipitation experiments showed that
      EBP50 interacts with EGF receptor via the PDZ2 domain and with focal adhesion
      kinase (FAK) via the C-terminal ERM domain. EBP50 promoted the formation of a
      complex containing both EGF receptor and FAK. Phosphorylation of Tyr-925 of FAK
      in response to EGF was significantly reduced in KO cell compared to WT cells. The
      residence time of FAK in focal adhesions-determined by fluorescence recovery
      after photobleaching-was increased in WT cells. Collectively, these studies
      indicate that EBP50, by scaffolding EGF receptor and FAK, facilitates activation
      of FAK, focal adhesion turnover, and migration of VSMC.

PMID- 22974530
TI  - Baseline epicardial adipose tissue adiponectin levels predict cardiovascular
      outcomes: a long-term follow-up study.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) produces a wide range of adipokines
      and has recently been linked to the physiopathology of cardiovascular (CV) and
      metabolic diseases. We aimed to study whether EAT and subcutaneous (SAT)
      adiponectin and leptin expression levels are associated with CV complications
      during long-term follow-up. METHODS AND RESULTS: EAT and SAT samples were
      obtained during surgery - mainly CABG (n=77) - from 137 patients (mean age 69.9
      years, 31% women). Adiponectin and leptin mRNA levels were analyzed by RT-PCR.
      Plasma adiponectin levels were determined in a subsample of subjects (n=43).
      Thirty-four patients developed CV complications during 41 (SD 23) months of mean
      follow-up. Patients with CV events had lower EAT and SAT adiponectin levels at
      baseline (12.4 (3.0) vs. 15.7 (3.8) a.u., P=0.001; and 13.7 (2.6) vs. 15.7 (4.4)
      a.u., P=0.048, respectively). However, baseline EAT and SAT leptin levels and
      plasma adiponectin levels were not significantly different between patients
      with/without CV events during follow-up. Cox proportional hazards models
      adjusting for covariates in stages revealed that only baseline EAT adiponectin
      levels and heart failure could predict CV events. CONCLUSIONS: EAT adiponectin
      levels are strong predictors of CV prognosis in patients with CV diseases. EAT is
      likely to play a major role in the development of CV complications mainly through
      local effects.

PMID- 22974529
TI  - Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony
      Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of
      stimulation by CSF-1 and Interleukin 34.
AB  - Macrophage Colony Stimulating Factor (CSF-1) controls the survival,
      differentiation and proliferation of cells of the mononuclear phagocyte system. A
      second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its
      physiological role is not yet known. The domestic pig provides an alternative to
      traditional rodent models for evaluating potential therapeutic applications of
      CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed
      active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor
      dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF
      1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the
      human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active
      on mouse, human, cat and dog cells. IL-34 was previously shown to be species
      specific, with mouse and human proteins demonstrating limited cross-species
      activity. The pig CSF-1R was equally responsive to both mouse and human IL-34.
      Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R
      complexes, we discuss the molecular basis for the species specificity.

PMID- 22974531
TI  - Age-related changes in phagocytic activity and production of pro-inflammatory
      cytokines by lipopolysaccharide stimulated porcine alveolar macrophages.
AB  - The aim of the present study was to determine the age-related changes of
      phagocytic capacity and the kinetic production of cytokines in lipopolysaccharide
      stimulated porcine alveolar macrophages. For this purpose, AMs were isolated from
      5 (newborn), 40 (post-weaned) and 120 (young) day old pigs. Results of
      phagocytosis assay showed that AMs from newborn piglets had less phagocytic
      capacity than those of young pigs (P<0.05). For the kinetics study, cells and
      supernatant were collected at 1, 6, 12, 24, 36 and 48 h after LPS stimulation for
      quantification of cytokine mRNA and protein by quantitative real-time PCR and
      ELISA, respectively. The kinetics results showed that AMs from newborn piglets
      were significantly less capable of producing IL1beta, IL6, IL12beta, TNFalpha and
      IL8 than post-weaned piglets or young pigs. IL18 mRNA did not show significant
      differences between ages. MIP2 and MCP1 mRNA was higher in young pigs. Hence,
      higher production of cytokines by AMs may be the surfactant factors in the
      pulmonary host defense system. These results indicate that AMs from newborn
      piglets might be functionally immature, which may lead to increased
      susceptibility to lung infections. Future studies of cytokine kinetics in more
      animals are clearly needed to confirm these results across a wider age range.

PMID- 22974532
TI  - Low-frequency ultrasound-induced transport across non-raft-forming ternary lipid
      bilayers.
AB  - We examined the effect of bilayer composition on membrane sensitivity to low
      frequency ultrasound (LFUS) in bilayers composed of ternary mixtures of 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), dipalmitoyl-phosphocholine
      (DPPC), and cholesterol. The phase diagram of this system does not display
      macroscopic phase coexistence between liquid phases (although there are
      suggestions that there is coexistence between a liquid and a solid phase).
      Samples from across the composition space were exposed to 20 kHz, continuous wave
      ultrasound, and the response of the bilayer was quantified using steady-state
      fluorescence spectroscopy to measure the release of a self-quenching dye,
      calcein, from large unilamellar vesicles. Dynamic light scattering measurements
      indicate that, in this system, release proceeds primarily by transport through
      the vesicle bilayer. While vesicle destruction might account, at least in part,
      for the light scattering trends observed, evidence of destruction was not as
      obvious as in other lipid systems. Values for bilayer permeability are obtained
      by fitting release kinetics to a two-film theory mathematical model. The
      permeability due to LFUS is found to increase with increasing DPPC content, as
      the bilayer tends toward the solid-ordered phase. Permeability, and thus
      sensitivity to LFUS, decreases with either POPC or cholesterol mole fractions. In
      the liquid regime of this system, there is no recorded phase transition; thus
      cholesterol is the determining factor in release rates. However, the presence of
      domain boundaries between distinctly differing phases of liquid and solid is
      found to cause release rates to more than double. The correlation of permeability
      with phase behavior might prove useful in designing and developing therapies
      based on ultrasound and membrane interactions.

PMID- 22974534
TI  - A novel in vitro loading system for high frequency loading of cultured tendon
      fascicles.
AB  - Tendons are known to adapt to their mechanical environment, however high
      frequency low magnitude (HFLM) loading regimes (10-50Hz), which are effective in
      promoting bone anabolic effects, have not been investigated in controlled
      conditions in tendon. In vitro loading systems (IVLS) enable precise
      characterisation of the link between their controlled mechanical environment and
      cultured tissue biological response. We report a novel IVLS design using an
      applied magnetic field to produce time varying loading in cultured rat tail
      tendon fascicles (RTTF). The design was validated through magnetic flux, load
      cell and viability measurements, and we report the results of preliminary
      experiments testing the hypothesis that an HFLM loading regime will maintain the
      biochemical and mechanical properties of fresh RTTF in culture over 7 days.
      Tissue viability was maintained for 7 days under all loading conditions, and the
      average peak load applied to RTTFs using the IVLS at 20Hz was 0.125N. RTTFs
      cultured for 7 days with HFLM loading showed a trend for a higher tangent modulus
      than fresh tissue, and significantly higher modulus than unloaded RTTFs. GAG
      content of HFLM cultured RTTFs was not significantly changed from that of fresh
      RTTFs. This novel, validated IVLS will provide new knowledge of tendon
      mechanobiology and has already shown the potential of clinically relevant HFLM
      loading for influencing tendon biology.

PMID- 22974533
TI  - Multimodal hypoxia imaging and intensity modulated radiation therapy for
      unresectable non-small-cell lung cancer: the HIL trial.
AB  - BACKGROUND: Radiotherapy, preferably combined with chemotherapy, is the treatment
      standard for locally advanced, unresectable non-small cell lung cancer (NSCLC).
      The tumor response to different therapy protocols is variable, with hypoxia known
      to be a major factor that negatively influences treatment effectiveness.
      Visualisation of tumor hypoxia prior to the use of modern radiation therapy
      strategies, such as intensity modulated radiation therapy (IMRT), might allow
      optimized dose applications to the target volume, leading to improvement of
      therapy outcome. (18)F-fluoromisonidazole dynamic positron emission tomography
      and computed tomography ((18) F-FMISO dPET-CT) and functional magnetic resonance
      imaging (functional MRI) are attractive options for imaging tumor hypoxia.
      METHODS/DESIGN: The HIL trial is a single centre study combining multimodal
      hypoxia imaging with (18) F-FMISO dPET-CT and functional MRI, with intensity
      modulated radiation therapy (IMRT) in patients with inoperable stage III NSCLC.
      15 patients will be recruited in the study. All patients undergo initial FDG PET
      CT and serial (18) F-FMISO dPET-CT and functional MRI before treatment, at week 5
      of radiotherapy and 6 weeks post treatment. Radiation therapy is performed as
      inversely planned IMRT based on 4D-CT. DISCUSSION: Primary objectives of the
      trial are to characterize the correlation of (18) F-FMISO dPET-CT and functional
      MRI for tumor hypoxia imaging in NSCLC and evaluate possible effects of radiation
      therapy on tumor re-oxygenation. Further objectives include the generation of
      data regarding the prognostic value of (18) F-FMISO dPET-CT and functional MRI
      for locoregional control, progression free survival and overall survival of NSCLC
      treated with IMRT, which will form the basis for larger clinical trials focusing
      on possible interactions between tumor oxygenation and radiotherapy outcome.
      TRIAL REGISTRATION: The ClinicalTrials.gov protocol ID is NCT01617980.

PMID- 22974535
TI  - Stunting is an independent predictor of mortality in patients with cystic
      fibrosis.
AB  - BACKGROUND & AIMS: Some studies have shown a direct relationship between
      nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting,
      defined as a percentage of the ideal body weight for age, has been shown to be an
      independent predictor of mortality in CF. With respect to height only two studies
      were performed and these studies suggested that stunting is an important
      determinant of survival but both did not adjust statistical analysis for
      confounding variables. We aimed at determining the association between stunting
      and risk of mortality in CF patients. METHODS: 393 CF patients older than 6 years
      of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a
      nested case-control study. Stunting was defined by a height percentile < 5th. We
      performed a multivariate statistical analysis including height percentile and the
      following possible confounding variables: age, gender, Body Mass Index (BMI),
      Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related
      diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia.
      RESULTS: In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting
      (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 < 40% of predicted (OR 10.60 [IC 95% 5.43
      20.67]) resulted the covariates that significantly predict the risk of mortality.
      CONCLUSIONS: Our study shows, for the first time, that stunting is a significant
      and independent risk factor for mortality in CF patients, and warrants an
      intervention of nutritional rehabilitation. Considering that nutritional
      interventions in stunted patients should be prolonged, are invasive and
      expensive, and might affect self-esteem and body image, their efficacy should be
      fully assessed by Randomised Controlled Trials.

PMID- 22974536
TI  - The cost effectiveness of genetic testing for CYP2C19 variants to guide
      thienopyridine treatment in patients with acute coronary syndromes: a New Zealand
      evaluation.
AB  - BACKGROUND: A recent clinical trial has demonstrated that patients with acute
      coronary syndromes (ACS) and the reduced function allele CYP2C19*2 (*2 allele),
      who are treated with thienopyridines, have an increased risk of adverse cardiac
      events with clopidogrel, but not with prasugrel. The frequency of the *2 allele
      varies by ethnicity and the Maoris, Asians and Pacific Islanders of New Zealand
      have a relatively high incidence. OBJECTIVE: Our objective was to evaluate, from
      a New Zealand health system perspective, the cost effectiveness of treating all
      ACS patients with generic clopidogrel compared with prasugrel, and also compared
      with the genetically guided strategy that *2 allele carriers receive prasugrel
      and non-carriers receive clopidogrel. METHODS: A decision-tree model consisting
      of five health states (myocardial infarction, stroke, bleeding, stent thrombosis
      and cardiovascular death) was developed. Clinical outcome data (two TRITON-TIMI
      38 genetic sub-studies) comparing clopidogrel and prasugrel for both *2 allele
      carriers and non-carriers were combined with the prevalence of the heterozygosity
      for the *2 allele in New Zealand Europeans (15%), Maoris (24%), Asians (29%) and
      Pacific Islanders (45%) to determine the predicted adverse event rate for the New
      Zealand population. National hospital diagnosis-related group (DRG) discharge
      codes were used to determine alternative adverse event rates, along with the
      costs of hospitalizations during the 15 months after patients presented with an
      ACS. The primary outcome measure was the incremental cost per QALY (calculated
      using literature-reported weights). Monte Carlo simulations and alternative
      scenario analysis based on both clinical trial and national hospital incidence
      were used. Additional analysis considered the overall TRITON-TIMI 38 rates. Costs
      (in New Zealand dollars [$NZ], year 2009 values) and benefits were discounted at
      3% per annum. RESULTS: Actual hospital-based adverse event rates were higher than
      those reported in the TRITON-TIMI 38 randomized controlled trial and the genetic
      sub-studies, especially for myocardial infarction and cardiovascular death, and
      for Maoris and Pacific Islanders. For both sources of adverse event rates,
      treating the population with prasugrel was associated with worse outcomes (QALYs)
      than clopidogrel. However, prasugrel became cost effective ($NZ31 751/QALY) when
      the overall TRITON-TIMI 38 rates were used. A genetic test to guide the selected
      use of prasugrel was cost effective ($NZ8702/QALY versus $NZ24 617/QALY) for
      hospital and clinical trial incidence, respectively. Based on the hospital rates,
      the genetically guided strategy was especially cost effective for Maoris
      ($NZ7312/QALY) and Pacific Islanders ($NZ7041/QALY). These results were robust to
      the sensitivity analysis, except the genetically guided strategy under the 15
      month clinical trial event rate scenario ($NZ168 748/QALY) did not remain cost
      effective under a $NZ50 000 threshold. CONCLUSIONS: Use of a genetic test to
      guide thienopyridine treatment in patients with ACS is a potentially cost
      effective treatment strategy, especially for Maoris and Pacific Islanders. This
      treatment strategy also has the potential to reduce ethnic health disparities
      that exist in New Zealand. However, the results comparing clopidogrel and
      prasugrel are sensitive to whether the genetic sub-studies or the overall TRITON
      TIMI 38 rates are used. While the national hospital event rates may be more
      appropriate for the New Zealand population, many assumptions are required when
      they are used to adjust the genetic sub-studies rates.

PMID- 22974537
TI  - Losing sight of the wood for the trees: some issues in describing and valuing
      health, and another possible approach.
AB  - BACKGROUND AND OBJECTIVE: The ability to value health in a way that allows the
      comparison of different conditions across a range of population groups is central
      to determining priorities in healthcare. This paper considers some of the
      concerns with the 'received wisdom' in valuing health--to describe it using a
      generic descriptive system and to value it using the hypothetical preferences of
      the general public. METHODS: The literature on the dimensions of health that
      matter most to people was reviewed and this paper discusses the use of global
      measures of subjective well-being (SWB) as a possible alternative. New analysis
      of the British Household Panel Survey was conducted to explore the relationship
      between life satisfaction and the preference-based quality-of-life measure the SF
      6D. The impact on life satisfaction of each level for each dimension of the SF-6D
      is estimated through a linear model predicting life satisfaction with the SF-6D
      levels as determinants. RESULTS: Valuing changes in the health of the general
      population via changes in life satisfaction would lead to different weights being
      attached to the different dimensions of health, as compared to a well used
      utility score in which weights are taken from general population preferences. If
      preferences elicited via standard gamble exercises are based only on a prediction
      of what it would be like to live in a particular health state, then these results
      suggest that reductions in physical functioning matter less than people imagine
      and reductions in mental health impact upon our lives more than preferences would
      suggest. CONCLUSIONS: Using data from the British Household Panel Survey, it is
      shown that a focus on SWB would place greater emphasis on mental health
      conditions. The implications for health policy are considered.

PMID- 22974538
TI  - A platyrrhine talus from the early Miocene of Peru (Amazonian Madre de Dios Sub
      Andean Zone).
AB  - The earliest platyrrhines have been documented from the late Oligocene of Bolivia
      (Salla) and from the early and early middle Miocene of middle and high latitudes
      (central Chile and Argentinean Patagonia). Recent paleontological field
      expeditions in Peruvian Amazonia (Atalaya, Cusco; Upper Madre de Dios Basin) have
      led to the discovery of a new early Miocene locality termed MD-61 ('Pinturan'
      biochronological unit, ~18.75-16.5 Ma [millions of years ago]). Associated with
      the typical Pinturan dinomyid rodent Scleromys quadrangulatus, we found a well
      preserved right talus of a small-bodied anthropoid primate (MUSM-2024). This new
      platyrrhine postcranial element displays a combination of talar features
      primarily found among the Cebidae, and more especially in the Cebinae. Its size
      approximates that of the talus of some living large marmosets or small tamarins
      (Cebidae, Callitrichinae). MUSM-2024 would thus document a tiny Saimiri-like
      cebine, with the body size of a large marmoset. Functionally, the features and
      proportions of MUSM-2024 indicate that this small primate was arboreal and
      primarily quadrupedal, agile, with frequent horizontal leaping and vertical
      clinging in its locomotor repertoire. This small talus is the first platyrrhine
      fossil to be found from Peru and the earliest primate fossil from northern South
      America. This new early Miocene taxon could be a stem cebid, thereby providing
      new evidence on the existence of some long-lived clades of modern platyrrhines.

PMID- 22974539
TI  - Predictors of breastfeeding exclusivity among migrant and Canadian-born women:
      results from a multi-centre study.
AB  - The objective of this study was to examine and compare predictors of
      breastfeeding exclusivity among migrant and Canadian-born women. As part of a
      longitudinal study, a sample of 1184 mothers were recruited from 12 hospitals in
      Canada and completed questionnaires at 1 and 16 weeks post-partum that included
      diverse questions from the following domains: demographic, social, migration,
      obstetrical, breastfeeding and maternal mood. After bivariate analysis,
      multivariate logistic regression analysis was completed to examine and compare
      predictors of exclusive breastfeeding at 16 weeks post-partum. Among migrant
      women, factors predictive of breastfeeding exclusivity included non-refugee
      immigrant or asylum-seeking status, residence in Toronto or Vancouver, maternal
      age of >=35 years, feels most comfortable in the country of origin or nowhere and
      higher Gender-related Development Index of the country of origin. Factors
      predictive of not exclusively breastfeeding included maternal age of <20 years,
      not planning to exclusively breastfeed, not making the decision to breastfeed
      before pregnancy and not exclusively breastfeeding at 1 week post-partum. Among
      Canadian-born women, factors predictive of a lower likelihood of breastfeeding
      exclusivity included not living with father of infant, infant neonatal intensive
      care unit admission, planned duration of exclusive breastfeeding for <6 months,
      not exclusively breastfeeding at 1 week post-partum and Edinburgh Postnatal
      Depression Scale score of >=10. The only similar risk factor predicting a lower
      likelihood of breastfeeding exclusivity between migrant and Canadian-born women
      was not exclusively breastfeeding at 1 week post-partum; all other risk factors
      were dissimilar, suggesting that these groups might benefit from different
      strategies to optimise breastfeeding outcomes.

PMID- 22974540
TI  - Simulated climate change causes immune suppression and protein damage in the
      crustacean Nephrops norvegicus.
AB  - Rising atmospheric carbon dioxide concentration is causing global warming, which
      affects oceans by elevating water temperature and reducing pH. Crustaceans have
      been considered tolerant to ocean acidification because of their retained
      capacity to calcify during subnormal pH. However, we report here that significant
      immune suppression of the Norway lobster, Nephrops norvegicus, occurs after a 4
      month exposure to ocean acidification (OA) at a level predicted for the year 2100
      (hypercapnic seawater with a pH lowered by 0.4 units). Experiments carried out at
      different temperatures (5, 10, 12, 14, 16, and 18 degrees C) demonstrated that
      the temperature within this range alone did not affect lobster immune responses.
      In the OA-treatment, hemocyte numbers were reduced by almost 50% and the
      phagocytic capacity of the remaining hemocytes was inhibited by 60%. The
      reduction in hemocyte numbers was not due to increased apoptosis in hematopoetic
      tissue. Cellular responses to stress were investigated through evaluating
      advanced glycation end products (AGE) and lipid oxidation in lobster
      hepatopancreata, and OA-treatment was shown to significantly increase AGEs',
      indicating stress-induced protein alterations. Furthermore, the extracellular pH
      of lobster hemolymph was reduced by approximately 0.2 units in the OA-treatment
      group, indicating either limited pH compensation or buffering capacity. The
      negative effects of OA-treatment on the nephropidae immune response and tissue
      homeostasis were more pronounced at higher temperatures (12-18 degrees C versus 5
      degrees C), which may potentially affect disease severity and spread. Our results
      signify that ocean acidification may have adverse effects on the physiology of
      lobsters, which previously had been overlooked in studies of basic parameters
      such as lobster growth or calcification.

PMID- 22974541
TI  - Development and validation of a new in vitro assay designed to measure contact
      allergen-triggered oxidative stress in dendritic cells.
AB  - BACKGROUND: Selected contact allergens are known to induce phenotypic and
      functional maturation of dendritic cells (DCs). Such changes occurring in DCs
      have been employed as assay readouts to predict skin-sensitizing potentials of
      small chemicals. OBJECTIVE: To respond to the urgent needs for reliable in vitro
      tests to identify contact allergens, we sought to develop a DC-based assay
      designed to detect early change(s) induced by sensitizers. METHODS: Signature
      gene expression profiles of skin sensitization were determined by GeneChip and
      quantitative RT-PCR analyses of RNA samples harvested from mouse skin and XS106
      DC line after exposure to dinitrofluorobenzene (DNFB). Production of reactive
      oxygen species (ROS) was examined indirectly by measuring the level of oxidative
      stress-XS106 DCs were labeled with a fluorescent dye, CM-H(2)DCFDA, exposed to
      test chemicals, and then examined for fluorescence signals by flow cytometer.
      RESULTS: DNFB induced abundant mRNA expression of several redox regulatory genes
      in both mouse skin and XS106DCs. Expression of these genes was inducible by
      hydrogen peroxide and blocked by a ROS inhibitor, diphenyleneiodonium. Rapid and
      significant ROS production was induced by 25 of the 28 tested skin sensitizers,
      but only by 3 of the 21 tested skin irritants. CONCLUSIONS: Our small-scale
      validation study demonstrates the practical utility of our DC-based ROS
      production assay to detect structurally diverse contact allergens with varying
      sensitizing potencies. It is tempting to speculate that ROS production in DCs may
      represent an early event during the sensitization phase.

PMID- 22974542
TI  - Induction of a systemic antiviral state in vivo in the domestic cat with a class
      A CpG oligonucleotide.
AB  - The evolution of cats as a solitary species has pressured feline viruses to
      develop highly efficient transmission strategies, the ability to persist within
      the host for long periods of time and the aptitude to adapt to natural and
      vaccine-induced immunological pressures. These characteristics render feline
      viruses particularly dangerous in catteries, shelters and rescue homes, were cats
      from different backgrounds live in close proximity. The possibility to induce
      short-term resistance of newcomer cats to a broad variety of viruses could help
      prevent the dissemination of viruses both within and outside such facilities.
      Oligonucleotides (ODN) containing unmethylated cytosine phosphate guanosine (CpG)
      motifs stimulate innate immune responses in mammals. We have previously shown
      that ODN 2216, a class A CpG ODN, promotes the expression by feline immune cells
      of potent antiviral molecules that increase resistance of feline fibroblastic and
      epithelial cell lines to five common feline viruses. With the aim to test the
      safety and extent of the biological effects of ODN 2216 in the domestic cat, we
      performed an initial in vivo experiment in which two cats were injected the
      molecule once subcutaneously and two additional cats received control treatments.
      No side effects to administration of ODN 2216 were observed. Moreover, this
      molecule induced the expression of the myxovirus resistance (Mx) gene, a marker
      for the instigation of innate antiviral processes, in blood as well as in oral,
      conjunctival and rectal mucosa cells, indicating systemic biological activity of
      the molecule with protective potential at viral entry sites. Mx mRNA levels were
      already elevated in blood 6h post injection of ODN 2216, reached peak levels
      within 24h and returned to basal values by 96-192 h after administration of the
      molecule. Similar induction patterns were observed in all analyzed mucosal cells.
      Plasma collected from treated cats at regular intervals until 96-192 h could
      moreover induce Mx mRNA expression in fcwf-4 cells and increase resistance of
      these cells to feline calicivirus inoculation. Finally, Mx mRNA levels measured
      in blood correlated with the degree of viral inhibition that was induced by
      plasma from the same cat and the same experimental time point. Our results
      altogether underline the promising potential of ODN 2216 in promoting antiviral
      defense mechanisms and inducing temporary resistance to viral infections in vivo
      in the domestic cat.

PMID- 22974543
TI  - Curculigo orchioides (Xian Mao) modifies the activity and protein expression of
      CYP3A in normal and Kidney-Yang Deficiency model rats.
AB  - AIM OF THE STUDY: In Chinese medicine clinics, traditional Chinese herbs are used
      to treat disorders of Yin and Yang balance, including Kidney-Yang Deficiency. The
      activity of the hepatic cytochrome P450 3A (CYP3A) is closely associated with
      body status. The aim of the present study is to investigate CYP3A enzymatic
      activity and CYP3A4 protein expression using a Kidney-Yang Deficiency rat model
      and furthermore to investigate the intervention effects of the Pungent-hot herb
      Xian Mao. This work contributes rationale for personalized medicine and enhances
      our understanding of herb-drug interactions. MATERIALS AND METHODS: Rats were
      randomly divided into three groups: the model group, the Xian Mao group and the
      intervention group (model rats treated with Xian Mao). The model rats were given
      an intramuscular injection of hydrocortisone for 14 days, and the control rats
      were given normal saline. The Xian Mao group consisted of normal rats treated
      with Xian Mao by oral gavage for 7 days. The intervention group was given Xian
      Mao for 7 days after treatment with hydrocortisone. The activity of CYP3A was
      detected by using the erythromycin-N-demethylase method. CYP3A4 protein
      expression level was detected by Western-blot. RESULTS: CYP3A enzymatic activity
      in the Kidney-Yang Deficiency rat was decreased by 44% compared to normal
      animals. The relative CYP3A4 protein expression level of the Kidney-Yang
      Deficiency rat (mean value 0.663+/-0.188) was 20% lower than that of normal rat
      (0.830+/-0.199). The in vitro data showed that CYP3A activity was significantly
      (P<0.001) inhibited (decreased by 59%) by Xian Mao concentrations of 1mg/mL. The
      in vivo data also showed that CYP3A activity was significantly decreased in the
      rats treated with the three doses of Xian Mao. The CYP3A4 protein expression was
      significantly decreased by Xian Mao treatment at the high and intermediate doses
      (30 and 20 g/kg, respectively) compared with the normal group. However, the
      intervention group (the Kidney-Yang Deficiency rat treated with Xian Mao at 20
      and 30 g/kg) showed an increased CYP3A activity and CYP3A4 protein expression
      compared with the herb-untreated model rats. CONCLUSION: CYP3A enzymatic activity
      and CYP3A4 protein expression could be inhibited by Xian Mao. The CYP3A activity
      and CYP3A4 expression in the Kidney-Yang Deficiency model rat were lower than
      that of normal rat but this deficiency could be rescued by treatment with Xian
      Mao.

PMID- 22974544
TI  - Achyranthes japonica exhibits anti-inflammatory effect via NF-kappaB suppression
      and HO-1 induction in macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Achyranthes japonica Nakai have been
      used in traditional herbal medicine for the treatment of edema and arthritis in
      Korea. AIM OF THE STUDY: In this study, we investigated the molecular mechanism
      responsible for anti-inflammatory effects of the aqueous extract of A. japonica
      roots (AJ) in LPS-stimulated macrophages. MATERIALS AND METHODS: Nitric oxide
      (NO) production and as inducible nitric oxide synthase (iNOS) expression were
      examined in TG-elicited peritoneal macrophages and RAW 264.7 cells. Cell
      viability was monitored by MTT assay. Protein and mRNA expressions were
      determined by Western blotting and RT-PCR, respectively. The activity of NF
      kappaB and Nrf2 were examined by EMSA, immunocytochemistry or reporter assay.
      RESULTS: AJ inhibited LPS-induced NO secretion as well as iNOS expression,
      without affecting cell viability. Furthermore, AJ suppressed LPS-induced NF
      kappaB activation, degradation of IkappaB-alpha, phosphorylation of extracellular
      signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. Further
      study demonstrated that AJ induced heme oxygenase-1 (HO-1) gene expression via
      nuclear translocation and transactivation of Nrf2. In addition, the inhibitory
      effects of AJ on iNOS expression were abrogated by small interfering RNA-mediated
      knock-down of HO-1. CONCLUSIONS: These results suggest that AJ suppresses LPS
      induced NO production and iNOS expression in macrophages through the inhibition
      of IkappaB/NF-kappaB and MAPK as well as the Nrf2-mediated HO-1 induction. These
      findings provide the scientific rationale for anti-inflammatory therapeutic use
      of A. japonica roots.

PMID- 22974545
TI  - Illicium verum extract inhibits TNF-alpha- and IFN-gamma-induced expression of
      chemokines and cytokines in human keratinocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Illicium verum Hook. f. (star anise) has been
      used in traditional medicine for treatment of skin inflammation, rheumatism,
      asthma, and bronchitis. This study investigated the anti-inflammatory effects of
      Illicium verum extract (IVE) in the human keratinocyte HaCaT cell line. MATERIALS
      AND METHODS: We investigated the effectiveness of IVE in tumor necrosis factor
      alpha (TNF-alpha)/interferon-gamma (IFN-gamma)-induced human keratinocytes. To
      measure the effects of IVE on chemokine and pro-inflammatory cytokine expression
      in HaCaT cells, we used the following methods: cell viability assay, reverse
      transcription-polymerase chain reaction, enzyme-linked immunosorbent assay,
      western blotting, and luciferase reporter assay. RESULTS: IVE inhibited the
      expression of TNF-alpha/IFN-gamma-induced mRNA and protein expression of thymus
      and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine
      (MDC/CCL22), interleukin (IL)-6, and IL-1beta. Furthermore, IVE decreased TNF
      alpha/IFN-gamma-induced mRNA expression of intercellular adhesion molecule-1
      (ICAM-1). IVE inhibited nuclear factor (NF)-kappaB translocation into the
      nucleus, as well as phosphorylation and degradation of IkappaBalpha. IVE
      inhibited TNF-alpha/IFN-gamma-induced NF-kappaB and signal transducer and
      activator of transcription (STAT)1 activation in a dose-dependent manner. In
      addition, IVE significantly inhibited activation of extracellular signal
      regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and Akt.
      Furthermore, IVE contained 2.14% trans-anethole and possessed significant anti
      inflammatory activities. CONCLUSIONS: IVE exerts anti-inflammatory effects by
      suppressing the expression of TNF-alpha/IFN-gamma-induced chemokines, pro
      inflammatory cytokines, and adhesion molecules via blockade of NF-kappaB, STAT1,
      MAPK, and Akt activation, suggesting that IVE may be a useful therapeutic
      candidate for inflammatory skin diseases, such as atopic dermatitis.

PMID- 22974546
TI  - Effect of the Miaoyao Fanggan sachet-derived isorhamnetin on TLR2/4 and NKp46
      expression in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Miaoyao Fanggan Sachets (MFS) has long been used
      as a folk medicine for the prevention of influenza in Southeast of Guizhou
      Province, China. However, the precise immunological mechanisms by which MFS
      confers protection have not been defined. STUDY AIM: To explore the effects of
      MFS on innate immune system responses using a cold stress-induced immune
      impairment model as a means of examining MFS-mediated influenza prevention. We
      investigated the effects of MFS on toll-like receptor 2 and 4 (TLR2/4) gene and
      protein expression levels and on the percentage of NKp46(+) cells present in
      serum. No overt toxicity was observed following continuous administration of MFS
      at high doses. METHODS: Kunming male mice (n=40) were randomly divided into 4
      groups consisting of the continuous inhalation Sachet group, Yu-Ping-Feng powder
      (YPF-P) gavage positive control group, discontinuous inhalation MFS group and
      untreated controls. After 4 weeks, mice were sacrificed and lungs harvested. The
      expression of toll-like receptors 2 and 4 (TLR2/4) gene and protein levels was
      assessed using real-time polymerase chain reaction (RT-PCR) and Western blot
      analyses, respectively. An additional 60 Kunming mice were randomly divided into
      6 groups comprised of a blank control group, continuous MFS inhalation group, an
      immune-compromised continuous MFS inhalation group, an immuno-compromised group,
      an immune-compromised MFS discontinuous inhalation group and an immune
      compromised positive control group. Immune suppression was induced by cold stress
      (4  degrees C/4 h daily for 3 days) and mice were treated with MFS or YPF-P
      before cold stress treatments. Immuno-compromised mice were treated with MFS
      continuously or intermittently, or treated with YPF-P. Blood samples were
      collected and examined for natural killer cells based on positive NKp46 staining.
      The isorhamnetin associated with MFS-induced immune modulation was obtained from
      'wo ga le' which is considered to be a major component of MFS, and analyzed by
      HPLC. RESULTS: Mice continuously inhaling MFS showed a moderate increase in
      TLR2/4 mRNA and protein levels compared to mice in the control and discontinuous
      inhalation groups. MFS significantly increased the TLR2/4 expression in a dose
      dependent manner. Furthermore, there was also a slightly significant increase in
      the number of NKp46(+) cells in the continuous inhalation group compared to
      controls and discontinuous inhalation group. Pretreatment with MFS partially
      prevented cold stress-induced inhibition of NKp46(+) cells. HPLC analysis of the
      'wo ga le' associated with immune function identified the major component to be
      isorhamnetin. CONCLUSIONS: Taken together, these data suggested that MFS
      significantly enhanced TLR2/4 expression levels and the number of NKp46(+) cells
      in mice and moderately affected innate immune responses associated with
      protection against influenza, suggesting that isorhamnetin in the MFS enhanced
      innate immune potency. The use of MFS for the prevention of various respiratory
      tract infections can be attributed to its antimicrobial properties. In a pilot
      study, a large quantity (40 g) was administered over a prolonged period did not
      produce apparent toxicity.

PMID- 22974547
TI  - The fate of duplicated genes in a polyploid plant genome.
AB  - Polyploidy is generally not tolerated in animals, but is widespread in plant
      genomes and may result in extensive genetic redundancy. The fate of duplicated
      genes is poorly understood, both functionally and evolutionarily. Soybean
      (Glycine max L.) has undergone two separate polyploidy events (13 and 59 million
      years ago) that have resulted in 75% of its genes being present in multiple
      copies. It therefore constitutes a good model to study the impact of whole-genome
      duplication on gene expression. Using RNA-seq, we tested the functional fate of a
      set of approximately 18 000 duplicated genes. Across seven tissues tested,
      approximately 50% of paralogs were differentially expressed and thus had
      undergone expression sub-functionalization. Based on gene ontology and expression
      data, our analysis also revealed that only a small proportion of the duplicated
      genes have been neo-functionalized or non-functionalized. In addition, duplicated
      genes were often found in collinear blocks, and several blocks of duplicated
      genes were co-regulated, suggesting some type of epigenetic or positional
      regulation. We also found that transcription factors and ribosomal protein genes
      were differentially expressed in many tissues, suggesting that the main
      consequence of polyploidy in soybean may be at the regulatory level. 

PMID- 22974548
TI  - Development of a nutrient-dense food supplement for HIV-infected women in rural
      Kenya using qualitative and quantitative research methods.
AB  - OBJECTIVE: Formative research to facilitate the development, packaging and
      delivery of a culturally acceptable nutrition intervention for HIV-infected women
      in rural Kenya for an intervention trial. DESIGN: Focus group discussion on three
      areas: (i) ingredients and form of the nutrition intervention, (ii) packaging and
      delivery and (iii) monitoring of adherence. Two single-blind taste tests with
      eleven different porridge formulations of various combinations of maize flour,
      soyabeans, peanuts, sorghum, mung beans, dried fish, raisins and dried whole
      milk. Follow-up acceptability focus group discussion was also conducted. SETTING:
      Voi, Kenya, community based. SUBJECTS: Focus group discussion and two taste tests
      (twenty-one women aged 16-55 years). Follow-up acceptability focus group
      discussion (four women enrolled in intervention trial). RESULTS: The preferred
      porridge for taste consisted of maize, soyabeans and peanuts. For animal protein,
      dried whole milk and dried fish were used. Although the women disliked the taste
      of dried fish, it was acceptable if added in small undetectable quantities. Sugar
      over lime was favoured for taste. Women believed they could consume at least two
      cups of porridge per day without displacing their usual meals. The optimal
      delivery interval was believed to be every two weeks in individual serving
      packages. Women who had been consuming porridge for several weeks felt the taste
      was acceptable for long-term consumption. CONCLUSIONS: This formative research
      resulted in the development, packaging and delivery of a nutrient-dense food
      supplement using local ingredients to meet the dietary needs of the population
      and acceptable for daily consumption by women in Kenya for evaluation in an
      intervention trial.

PMID- 22974549
TI  - Unique and potent effects of acute ibogaine on zebrafish: the developing utility
      of novel aquatic models for hallucinogenic drug research.
AB  - An indole alkaloid, ibogaine is the principal psychoactive component of the iboga
      plant, used by indigenous peoples in West Africa for centuries. Modulating
      multiple neurotransmitter systems, the drug is a potent hallucinogen in humans,
      although its psychotropic effects remain poorly understood. Expanding the range
      of model species is an important strategy for translational neuroscience
      research. Here we exposed adult zebrafish (Danio rerio) to 10 and 20mg/L of
      ibogaine, testing them in the novel tank, light-dark box, open field, mirror
      stimulation, social preference and shoaling tests. In the novel tank test, the
      zebrafish natural diving response (geotaxis) was reversed by ibogaine, inducing
      initial top swimming followed by bottom dwelling. Ibogaine also attenuated the
      innate preference for dark environments (scototaxis) in the light-dark box test.
      While it did not exert overt locomotor or thigmotaxic responses in the open field
      test, the drug altered spatiotemporal exploration of novel environment, inducing
      clear preference of some areas over others. Ibogaine also promoted 'mirror'
      exploration in the mirror stimulation test, disrupted group cohesion in the
      shoaling test, and evoked strong coloration responses due to melanophore
      aggregation, but did not alter brain c-fos expression or whole-body cortisol
      levels. Overall, our results support the complex pharmacological profile of
      ibogaine and its high sensitivity in zebrafish models, dose-dependently affecting
      multiple behavioral domains. While future investigations in zebrafish may help
      elucidate the mechanisms underlying these unique behavioral effects, our study
      strongly supports the developing utility of aquatic models in hallucinogenic drug
      research. High sensitivity of three-dimensional phenotyping approaches applied
      here to behavioral effects of ibogaine in zebrafish provides further evidence of
      how 3D reconstructions of zebrafish swimming paths may be useful for high
      throughput pharmacological screening.

PMID- 22974550
TI  - A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and
      nicotine seeking but does not affect inhibitory response control in Wistar rats.
AB  - Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT(6))
      receptors in the regulation of addictive behavior. In the present study, our aim
      was to investigate whether the novel highly selective 5-HT(6) receptor antagonist
      compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats.
      We have also studied whether CMP 42 had beneficial effects in a model of impulse
      control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats
      were trained to nose poke to receive intravenous infusions of nicotine or an
      ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to
      investigate the effects on nicotine self-administration. Rats were also tested
      for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the
      effects of CMP 42 were studied on the number of anticipatory responses in the 5
      CSRTT. CMP 42 was effective in reducing nicotine self-administration and
      reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also
      effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In
      contrast, CMP 42 did not affect anticipatory responding at doses tested,
      indicating no effects on impulse control. These results add to a body of evidence
      implicating the 5-HT(6) receptor as a viable target for the control of drug
      abuse. Specifically, we demonstrated for the first time effects on nicotine self
      administration and on nicotine and ethanol reinstatement. Further, these effects
      are probably not mediated by effects on impulse control.

PMID- 22974551
TI  - Seasonal and sex differences in the hippocampus of a wild rodent.
AB  - Studies across and within species suggest that hippocampus size is sexually
      dimorphic in polygamous species, but not in monogamous species. Although
      hippocampal volume varies with sex, season and mating system, few studies have
      simultaneously tested for sex and seasonal differences. Here, we test for sex and
      seasonal differences in the hippocampal volume of wild Richardson's ground
      squirrels (Urocitellus richardsonii), a polygamous species that lives in
      matrilineal, kin-based social groups and has profound sex differences in
      behavior. Based on the behavior and ecology of this species, we predicted that
      males would have a significantly larger hippocampus than females and that the
      hippocampus would be largest in males during the breeding season. Analyses of
      both absolute and relative volumes of the hippocampus yielded a significant
      difference between the sexes and seasons as well as an interaction between the
      two such that non-breeding males have significantly larger hippocampal volumes
      than breeding males or females from either season. Dentate gyrus, CA1 and CA3
      subfield volumes were generally larger in the non-breeding season and in males,
      but no significant interaction effects were detected. This sex and seasonal
      variation in hippocampal volume is likely the result of their social organization
      and male-only food caching behavior during the non-breeding season. The
      demonstration of a sex and seasonal variation in hippocampal volume suggests that
      Richardson's ground squirrel may be a useful model for understanding hippocampal
      plasticity within a natural context.

PMID- 22974552
TI  - Sleep deprivation alters phosphorylated CREB levels in the amygdala: relationship
      with performance in a fear conditioning task.
AB  - We investigated the relationship between deficits in fear memory induced by sleep
      deprivation and pCREB expression in the basal and central nuclei of the amygdala.
      Sleep deprivation reduced pCREB expression in the central nucleus compared to
      control or sleep recovered groups, and in the basal nucleus only compared to
      sleep recovered group. Moreover, 24h of sleep recovery prior to training
      prevented changes in both pCREB expression and performance.

PMID- 22974553
TI  - Occupational exposure during remediation works at a uranium tailings pile.
AB  - The aim of this study was to assess by different approaches the occupational
      exposure during the remediation of a tailings dam in an abandoned uranium mining
      site, with an area of about 13.3 ha and an estimated volume of 1.39 million m3. A
      hypothetical scenario was created in which the workers involved in the
      remediation activities were exposed to radiation through both internal and
      external pathways. It was intended to assess quantitatively the potential
      exposure of the workforce involved in the remediation works, focussing
      particularly on the inhalation of radon and on the gamma irradiation from the
      contaminated soil. Different methodologies were considered based on a
      deterministic and a probabilistic approach for dose assessment and risk
      assessment, respectively. The deterministic approach typically employs a highly
      "conservative" single value for each input parameter. The probabilistic approach
      employs sensitivity and uncertainty analysis of input parameters using
      probabilistic distributions of the sensitive parameters. The results indicate
      that annual effective dose limit for occupational exposure (worst scenario case
      created) may reach a significant fraction of occupational radiation protection
      limits. This is also stressed by the values obtained for the occupational risk
      estimated by Monte Carlo methodology using probabilistic distributions for the
      input parameters. The results also showed that the pathway with the highest dose
      does not necessarily correspond to the pathway with the highest risk.
      Nevertheless, it is well known that probabilistic analysis generally produces
      more realistic results.

PMID- 22974554
TI  - Effects of five daily high-frequency rTMS on Stroop task performance in aging
      individuals.
AB  - Previous evidence suggests that high-frequency repetitive transcranial magnetic
      stimulation (HF-rTMS) improves inhibitory control in healthy young adults. Little
      is known as to whether HF-rTMS would show similar facilitation effects in older
      adults undergoing normal aging. We recruited 16 healthy elderly adults and
      randomly assigned them to either a 10 Hz HF-rTMS or sham stimulation group. Five
      daily stimulation sessions over the left dorsolateral prefrontal cortex were
      given to each participant. Changes in inhibitory control were assessed using a
      modified Stroop task. Participants performed the Stroop task twice, 1 day before
      and after the five daily stimulations. We found that participants in the active
      HF-rTMS stimulation group showed improved performance in reaction time during
      incongruent trials (i.e. those with distracting information) after HF-rTMS
      treatment compared with pre-treatment trials. To the best of our knowledge, this
      study is one of the first studies demonstrating that daily HF-rTMS can improve
      attentional control in normally aging individuals.

PMID- 22974555
TI  - Counterfactual thinking and reward processing: an fMRI study of responses to
      gamble outcomes.
AB  - The process of comparing obtained outcomes to alternative possible outcomes,
      known as counterfactual thinking, is inescapable in daily life; however, the
      neurocognitive mechanisms underlying counterfactual thinking and how they
      influence emotional responses to better and worse outcomes is not well
      understood. We conducted an event-related functional magnetic resonance imaging
      (fMRI) gambling study in which participants were informed of two equally possible
      outcomes of a card gamble before they selected a card. Participants reported
      experiencing mixed emotions (i.e., both positive and negative affect) for
      disappointing wins (winning the lesser of two amounts) and relieving losses
      (losing the lesser of two amounts). Neuroimaging results supported the hypothesis
      that these mixed emotions were associated with activation of a fronto-parietal
      network, which subsequently influenced processing in reward and punishment
      regions (dorsal and ventral striatum, right anterior insula). The fronto-parietal
      network was sensitive to outcomes that resulted in mixed emotions, whereas reward
      and punishment regions were sensitive to comparisons between obtained and
      unobtained outcomes. These findings provide insight into the neurocognitive
      mechanisms underlying the mixed emotional experiences that result from
      counterfactual comparisons, and inform our understanding of how the brain is
      optimized to use the wealth of environmental information to inform current and
      future behavior.

PMID- 22974556
TI  - Automated detection of white matter signal abnormality using T2 relaxometry:
      application to brain segmentation on term MRI in very preterm infants.
AB  - Hyperintense white matter signal abnormalities, also called diffuse excessive
      high signal intensity (DEHSI), are observed in up to 80% of very preterm infants
      on T2-weighted MRI scans at term-equivalent age. DEHSI may represent a
      developmental stage or diffuse microstructural white matter abnormalities.
      Automated quantitative assessment of DEHSI severity may help resolve this debate
      and improve neonatal brain tissue segmentation. For T2-weighted sequence without
      fluid attenuation, the signal intensity distribution of DEHSI greatly overlaps
      with that of cerebrospinal fluid (CSF) making its detection difficult.
      Furthermore, signal intensities of T2-weighted images are susceptible to magnetic
      field inhomogeneity. Increased signal intensities caused by field inhomogeneity
      may be confused with DEHSI. To overcome these challenges, we propose an algorithm
      to detect DEHSI using T2 relaxometry, whose reflection of the rapid changes in
      free water content provides improved distinction between CSF and DEHSI over that
      of conventional T2-weighted imaging. Moreover, the parametric transverse
      relaxation time T2 is invulnerable to magnetic field inhomogeneity. We conducted
      computer simulations to select an optimal detection parameter and to validate the
      proposed method. We also demonstrated that brain tissue segmentation is further
      enhanced by incorporating DEHSI detection for both simulated preterm infant brain
      images and in vivo in very preterm infants imaged at term-equivalent age.

PMID- 22974557
TI  - Electrical stimulation ameliorates light-induced photoreceptor degeneration in
      vitro via suppressing the proinflammatory effect of microglia and enhancing the
      neurotrophic potential of Muller cells.
AB  - Many types of electrical stimulation (ES) devices have been shown to promote the
      survival of degenerated neural cells, such as dopaminergic neurons in the medial
      forebrain bundle-transected rats, ischemic-injured cortical neurons and inner-and
      outer-nuclear-layer cells in degenerated retina. Using a rat photic injury model,
      our lab previously proved the neuroprotective effect of transcorneal electrical
      stimulation (TCES) on apoptotic photoreceptor cells. To delineate the mechanisms
      that might underlie this process, the effects of ES on light-damaged
      photoreceptor degeneration-induced microglia and Muller cell activation were
      investigated in the present in vitro study. Our data showed that ES (3 ms, 20 Hz,
      300-1600 MUA) increased survival among light-reared cone-derived cells (661W)
      cultured alongside microglia or Muller cells analyzed by LDH and TUNEL assays.
      The degree of rescue was found to depend on the different intensities of the ES
      current. The immunocytochemistry revealed that ES significantly decreased the
      numbers of activated microglia cells with ameboid shapes and increased the
      numbers of reactive gliotic Muller cells with larger soma when they were co
      cultured with light-damaged 661W cells. Real-time RT-PCR and Western blotting
      indicated that ES which was applied to different co-cultures and 661W cell
      conditioned media (661WCM)-treated glia cultures had a prominent inhibitive
      effect on the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)
      alpha in microglia and a positive regulative effect on the production of brain
      derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in
      Muller cells. The death rate of light-exposed 661W cells cultured with microglia
      was decreased significantly by the addition of neutralizing antibodies against IL
      1beta and TNF-alpha. On the other hand, the death rate of light-exposed 661W
      cells cultured with Muller cells was prominently increased when the co-culture
      was incubated in the presence of neutralizing antibody against BDNF while anti
      CNTF neutralizing antibody did not induce additional exacerbation of the cell
      death among those 661W cells. These findings indicate the feasibility of using ES
      to create a nurturing environment for light-damaged photoreceptor cells. This
      environment is characterized by diminished microglial activation and fortified
      Muller cells reactive gliosis, which may have great potential in ameliorating
      photoreceptor damage. In this way, ES was here determined to be a novel, potent
      therapeutic option for delaying the progression of photoreceptor degeneration in
      patients suffering from retinitis pigmentosa (RP).

PMID- 22974558
TI  - Cholinergic gating of hippocampal auditory evoked potentials in freely moving
      rats.
AB  - As perturbations in auditory filtering appear to be a candidate trait marker of
      schizophrenia, there has been considerable interest in the development of
      translational rat models to elucidate the underlying neural and neurochemical
      mechanisms involved in sensory gating. This is the first study to investigate the
      effects of the non-selective muscarinic antagonist scopolamine, the muscarinic M1
      antagonist biperiden and the cholinesterase inhibitor donepezil (also in
      combination with scopolamine and biperiden) on auditory evoked potentials (AEPs)
      and sensory gating. In the saline condition, only the N50 peak displayed sensory
      gating. Scopolamine and biperiden both disrupted sensory gating by increasing N50
      amplitude for the S2 click. Donepezil was able to fully reverse the effects of
      biperiden on N50 sensory gating, but had residual effects when combined with
      scopolamine; i.e., it enhanced sensory gating by increasing N50 amplitude of the
      S1 stimulus. Donepezil by itself improved sensory gating by enhancing N50
      amplitude of S1, and reducing N50 amplitude of the S2 click. In conclusion, due
      to its relatively more selective effects biperiden is to be preferred over
      scopolamine as a means for pharmacologically inducing cholinergic impairments in
      auditory processing in healthy rats. Changes in auditory processing and sensory
      gating induced by cholinergic drugs may serve as a translational model for aging
      instead of schizophrenia. 

PMID- 22974559
TI  - Mutant huntingtin regulates EGF receptor fate in non-neuronal cells lacking wild
      type protein.
AB  - Huntingtin (htt) is a scaffold protein localized at the subcellular level and is
      involved in coordinating the activity of several protein for signaling and
      intracellular transport. The emerging properties of htt in intracellular
      trafficking prompted us to study the role of mutant htt (polyQ-htt) in the
      intracellular fate of epidermal growth factor receptor (EGFR), whose activity
      seems to be strictly regulated by htt. In particular, to evaluate whether protein
      trafficking dysfunction occurs in non-neuronal cells in the absence of functional
      htt, we monitored the EGFR protein in fibroblasts from homozygotic HD patients
      and their healthy counterpart. We found that polyQ-htt controls EGFR degradation
      and recycling. Lack of wild-type htt caused alteration of the ubiquitination
      cycle, formation of EGFR-incorporating high-molecular weight protein aggregates
      and abnormal EGFR distribution in endosomes of the degradation and recycling
      pathways after EGF stimulation. PolyQ-htt-induced alteration of EGFR trafficking
      affected cell migration and proliferation, at least in part, through inhibition
      of ERK signaling. To our knowledge the data here reported represent the first
      signaling and phenotypic characterization of polyQ-htt involvement in the
      modulation of growth factor stimulation in non-neuronal cells.

PMID- 22974560
TI  - Balance of brain oxytocin and vasopressin: implications for anxiety, depression,
      and social behaviors.
AB  - Oxytocin and vasopressin are regulators of anxiety, stress-coping, and sociality.
      They are released within hypothalamic and limbic areas from dendrites, axons, and
      perikarya independently of, or coordinated with, secretion from neurohypophysial
      terminals. Central oxytocin exerts anxiolytic and antidepressive effects, whereas
      vasopressin tends to show anxiogenic and depressive actions. Evidence from
      pharmacological and genetic association studies confirms their involvement in
      individual variation of emotional traits extending to psychopathology. Based on
      their opposing effects on emotional behaviors, we propose that a balanced
      activity of both brain neuropeptide systems is important for appropriate
      emotional behaviors. Shifting the balance between the neuropeptide systems
      towards oxytocin, by positive social stimuli and/or psychopharmacotherapy, may
      help to improve emotional behaviors and reinstate mental health.

PMID- 22974561
TI  - Low plasma DHEA-S increases mortality risk among male hemodialysis patients.
AB  - OBJECTIVE: The incidence of chronic kidney disease (CKD) is on the rise. CKD
      patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD
      patients have several endocrine disorders, including low levels of
      dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of
      DHEA-S are associated with high CVD and all-cause mortality. The aim of this
      study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD
      patients on hemodialysis. METHOD: This was a single-center prospective cohort
      study on two hundred CKD patients on hemodialysis, which assessed the prognostic
      value of plasma DHEA-S on their survival. RESULT: We found that plasma DHEA-S
      levels were negatively associated with age, and positively associated with
      dialysis duration and plasma creatinine, albumin, and phosphate levels in
      hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus,
      congestive heart failure, and chronic obstructive pulmonary disease), poorer
      fluid control which was evaluated by higher cardiothoracic ratio, and low plasma
      creatinine and albumin levels seemed to have poor prognosis in hemodialysis men.
      Furthermore, low plasma DHEA-S levels were significantly associated with CVD
      related [hazard ratio (HR)=3.877; P=0.021], non-CVD-related (HR=3.522; P=0.016),
      and all-cause mortality (HR=3.667; P=0.001) in hemodialysis men. But low plasma
      DHEA-S levels were not significantly associated with CVD-related, non-CVD
      related, and all-cause mortality in hemodialysis women. Multivariate Cox
      regression analysis suggested that low plasma DHEA-S levels are significantly and
      independently associated with all-cause mortality in hemodialysis men (HR=2.933;
      P=0.033). CONCLUSION: The study suggested that low plasma DHEA-S was
      independently and significantly associated with all-cause mortality in CKD
      hemodialysis men.

PMID- 22974562
TI  - Evolutionary stability of one-to-many mutualisms.
AB  - One-to-many mutualisms - interspecific cooperations in which each host individual
      can potentially interact with multiple symbiont individuals while each symbiont
      individual can only one host individual - are widely found in nature, while their
      evolutionary stability has not been explored. It has been often thought that
      partner choice can stabilize multi-player mutualisms. However, in one-to-many
      mutualisms partner choice is inevitably asymmetric between hosts and symbionts,
      which might destabilize the system. Here I develop a simple mathematical model
      for an obligate one-to-many mutualism, with explicitly considering imperfect
      ability of symbiont choice by hosts. I fix the trait of hosts and concentrate on
      the evolutionary dynamics of cooperativeness in symbiont population. Each host
      chooses a constant number of symbionts from a potential symbiont population, a
      fraction of which are chosen through preferential choice depending on
      cooperativeness of the symbionts, while the rest are through random choice. After
      the association between the host and the symbionts is established, the host
      offers a constant amount of resource to each associating symbiont. It spends a
      part of the resource to increase the fitness of the host in proportion to its
      cooperativeness, and the rest for its own reproduction. I show that pure
      mutualist population is evolutionarily stable when the fraction of preferential
      choice c is large and the strength of preferential choice k is small, otherwise
      mutualists and cheaters coexist. In addition, in the coexistence state the
      frequency of mutualists increases with c. In contrast, it decreases with k, while
      the cooperativeness of mutualists increases. The two factors offset against each
      other, so that the fitness gain of host remains constant.

PMID- 22974564
TI  - Dysplasia in inflammatory bowel diseases.
AB  - In both Crohn's disease and ulcerative colitis, the secondary prevention of
      colorectal cancer basically relies on the histological detection of dysplasia. In
      inflammatory bowel diseases, dysplasia identifies the subgroup of patients
      eligible for stricter surveillance (or prophylactic colectomy). In clinical
      practice, a number of issues may influence the benefits of clinico-pathological
      surveillance for inflammatory bowel disease patients with dysplasia, including:
      sampling errors, inconsistent biopsy assessments, patients' compliance with
      follow-up requirements, and how heath care is organized. Even in such a
      multifaceted context, it has been demonstrated that dysplasia surveillance is
      effective in reducing colorectal cancer-related mortality and morbidity. This
      paper focuses on current issues concerning the histological assessment of
      inflammatory bowel disease-associated dysplastic lesions.

PMID- 22974563
TI  - A mechanistic compartmental model for total antibody uptake in tumors.
AB  - Antibodies are under development to treat a variety of cancers, such as
      lymphomas, colon, and breast cancer. A major limitation to greater efficacy for
      this class of drugs is poor distribution in vivo. Localization of antibodies
      occurs slowly, often in insufficient therapeutic amounts, and distributes
      heterogeneously throughout the tumor. While the microdistribution around
      individual vessels is important for many therapies, the total amount of antibody
      localized in the tumor is paramount for many applications such as imaging,
      determining the therapeutic index with antibody drug conjugates, and dosing in
      radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time
      course of uptake is critical in determining when to take an image or deliver a
      secondary reagent. We present here a simple mechanistic model of antibody uptake
      and retention that captures the major rates that determine the time course of
      antibody concentration within a tumor including dose, affinity, plasma clearance,
      target expression, internalization, permeability, and vascularization. Since many
      of the parameters are known or can be estimated in vitro, this model can
      approximate the time course of antibody concentration in tumors to aid in
      experimental design, data interpretation, and strategies to improve localization.

PMID- 22974565
TI  - Oesophageal mucosal intercellular space diameter and reflux pattern in childhood
      erosive and non-erosive reflux disease.
AB  - BACKGROUND AND AIMS: We sought to compare intercellular space diameter in
      children with non-erosive and erosive reflux disease, and a control group. We
      also aimed to characterize the reflux pattern in erosive and non-erosive reflux
      disease patients, and to explore the relationship between intercellular space
      diameter values and reflux parameters. METHODS: Twenty-four children with non
      erosive reflux disease, 20 with erosive reflux disease, and 10 controls were
      prospectively studied. All patients and controls underwent upper endoscopy.
      Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter
      was measured using transmission electron microscopy. Non-erosive and erosive
      reflux disease patients underwent impedance-pH monitoring. RESULTS: Mean
      intercellular space diameter values were significantly higher in both non-erosive
      (0.9 +/- 0.2 MUm) and erosive reflux disease (1 +/- 0.2 MUm) compared to controls
      (0.5 +/- 0.2 MUm, p<0.01). No difference was found between the two patient
      groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline
      reflux events did not differ between the two patient groups. No difference was
      found in the mean intercellular space diameter between non-erosive reflux disease
      children with and without abnormal acid exposure time (1 +/- 0.3 vs. 0.9 +/- 0.2
      MUm). No correlation was found between any reflux parameter and intercellular
      space diameter values. CONCLUSIONS: Dilated intercellular space diameter seems to
      be a useful and objective marker of oesophageal damage in paediatric gastro
      oesophageal reflux disease, regardless of acid exposure. In childhood, different
      gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis
      of reflux pattern.

PMID- 22974566
TI  - Virtual unenhanced CT images acquired from dual-energy CT urography: accuracy of
      attenuation values and variation with contrast material phase.
AB  - AIM: To determine how representative virtual unenhanced (VNE) images are of true
      unenhanced (TNE) images when performing computed tomography (CT) urography on a
      dual-energy CT (DECT) system, and whether the images are affected by the contrast
      material phase. MATERIALS AND METHODS: In this retrospective, institutional
      review board-approved, Health Insurance Portability and Accountability Act
      (HIPAA)-compliant study, TNE were compared with VNE images derived from the
      nephrographic (VNEn) and excretory (VNEe) phases in 100 consecutive CT urograms.
      Two readers in consensus measured attenuation values of abdominal organs, fat,
      and renal lesions (>1 cm). Image noise was correlated with patient thickness.
      Detectability of renal stones was evaluated. Image quality and acceptability was
      assessed using a five-point scale. Expected dose saving by removing the TNE phase
      was calculated. RESULTS: VNE attenuation values of liver, renal parenchyma, and
      aorta were significantly different to TNE values (p < 0.05); spleen and fat
      attenuation values showed no significant difference. No significant difference
      was found between VNEn and VNEe images. Image noise was significantly greater in
      TNE images (p < 0.0001) and correlated with patient thickness. VNEn and VNEe
      images had sensitivities of 76.6 and 65.6% for detection of stones, identifying
      all stones greater than 3 and 4 mm, respectively. Both VNE images received
      significantly lower image quality scores than TNE images (p < 0.0001); however,
      the majority of images were deemed acceptable. The mean theoretical dose saving
      by removing the TNE phase was 35%. CONCLUSION: Although VNE images demonstrate
      high reader acceptability, accuracy of attenuation values and detection of small
      stones is limited. The contrast material phase, however, does not affect
      attenuation values. Further validation of VNE images is recommended prior to
      clinical implementation.

PMID- 22974567
TI  - Multidetector CT and MRI of ostial atresia of the coronary sinus, associated
      collateral venous pathways and cardiac anomalies.
AB  - AIM: To analyse the multidetector computed tomography (MDCT) and magnetic
      resonance imaging (MRI) findings in patients with atresia of the coronary sinus
      orifice (CSA). MATERIALS AND METHODS: MDCT findings of 15 consecutive adult
      patients with CSAs were retrospectively analysed. The patients underwent contrast
      enhanced electrocardiography-gated MDCT (n = 13) or both CT and MRI (n = 2).
      RESULTS: The mean size of the coronary sinus (CS) was 14.2 mm (range 5.5-24 mm)
      and 11 patients (73.3%) showed CS dilatation (diameter >=12 mm). The mean length
      of the atretic CS segment was 2.9 mm (range 0-8 mm). Different forms of venous
      collateral pathways were observed in the CSA patients. Nine (60%) of the 15 CSA
      patients had communication between the right atrium (RA; n = 6) or LA (n = 5) and
      CS via intraseptal veins; six patients (40%) had persistent left superior caval
      veins; communications were also observed between the CS and RA (n = 4) or LA (n =
      4); two patients had collateral venous pathways between dilated cardiac veins
      with RA; two patients had unroofing of the CS as outlet channels. Nine patients
      (60%) had cardiac anomalies: coronary artery fistula to the pulmonary artery (n =
      6) or left ventricular base and CS (n = 1), atrial septal defects (n = 2), and a
      ventricular septal defect (n = 1). CONCLUSION: CSA patients have venous
      collateral pathways and a high incidence of associated cardiovascular anomalies
      such as coronary artery fistulae and atrial septal defects.

PMID- 22974568
TI  - Uterine artery embolization for the management of secondary postpartum
      haemorrhage associated with placenta accreta.
AB  - AIM: To evaluate the efficacy and safety of uterine artery embolization for the
      management of secondary postpartum haemorrhage associated with placenta accreta.
      MATERIALS AND METHODS: Between January 2005 and August 2011, 45 women with
      placenta accreta, which was discovered during delivery, were managed
      conservatively in Peking Union Medical College Hospital. They did not experience
      severe bleeding during delivery. Ten patients (mean age 31 +/- 6.4 years)
      developed secondary postpartum haemorrhage and underwent uterine artery
      embolization. The complications, control of haemorrhage, and outcome of the
      placenta left inside the uterus were retrospectively reviewed. RESULTS: All
      patients underwent transcatheter embolization of bilateral uterine arteries. The
      median time between delivery and uterine artery embolization was 11 days (range 3
      76 days). The technical success rate of embolization was 100%. Bleeding was
      controlled in all patients during follow-up (11 +/- 6.9 months; range 3-24
      months), and no further bleeding occurred. One patient developed lower-extremity
      deep venous thrombosis after uterine artery embolization, and no other major
      complications occurred. The placentae that were left inside the uteri gradually
      decreased in size during follow-up, except in one case. Nine patients resumed
      normal menstruation. One patient subsequently became pregnant and had an
      uneventful intrauterine pregnancy carried to term. CONCLUSION: Uterine artery
      embolization is safe and effective for the management of secondary postpartum
      haemorrhage associated with placenta accreta.

PMID- 22974569
TI  - Diagnostic performance of CUBE MRI sequences of the knee compared with
      conventional MRI.
AB  - AIM: To evaluate the efficacy and efficiency of three-dimensional (3D) fast spin
      echo (FSE) with variable flip angle ("CUBE") magnetic resonance imaging (MRI) in
      knee imaging as compared with conventional MRI. MATERIALS AND METHODS: Twenty
      nine patients (single knee) with joint injuries of varying degrees were enrolled
      in this study between January, 2011 and December, 2011. All patients underwent
      conventional MRI and a fat-suppressed CUBE MRI sequence. All patients
      subsequently underwent knee arthroscopic surgery performed by an experienced
      orthopaedic surgeon within 2 weeks after the MRI examinations. With standard
      reference provided by arthroscopic results, the sensitivity, specificity, and
      accuracy of both the CUBE and conventional MRI techniques were calculated for
      detecting cartilage lesions, meniscus tears, and anterior cruciate ligament
      injuries, respectively. A chi-square test was used for statistical analysis with
      a level of significance of p < 0.05. RESULTS: For the evaluation of articular
      cartilage lesions, the CUBE sequence had higher sensitivity (70.9% versus 50.6%,
      p < 0.01), higher specificity (72.6% versus 58.9%, p < 0.05), and higher accuracy
      (71.8% versus 55.2%, p = 0.001) than conventional MRI. For the evaluation of
      meniscus tears, CUBE and conventional MRI had similar sensitivity, specificity,
      and accuracy (p = 0.20-0.55). Similarly, there was no significant difference in
      sensitivity, specificity, or accuracy between CUBE imaging and conventional
      imaging in the detection of anterior cruciate ligament injuries (p = 0.13-0.65).
      CONCLUSION: CUBE MRI has similar or superior sensitivity, specificity, and
      accuracy to a conventional imaging protocol in the comprehensive evaluation of
      knee joint injuries.

PMID- 22974570
TI  - Inflammatory myofibroblastic tumour of the maxillary sinus: CT and MRI findings.
AB  - AIM: To characterize the computed tomography (CT) and magnetic resonance imaging
      (MRI) findings of inflammatory myofibroblastic tumours (IMTs) of the maxillary
      sinus. MATERIALS AND METHODS: The imaging findings of eight patients with IMTs of
      the maxillary sinus were reviewed retrospectively. Of the eight patients, four
      patients underwent unenhanced and contrast-enhanced CT, and one patient underwent
      unenhanced CT only; three patients underwent unenhanced and contrast-enhanced
      MRI. RESULTS: Five cases of IMTs occurred in the left maxillary sinus, while
      three cases were right-sided. Four cases occupied the entire sinus, and the other
      four cases only partially occupied the sinus. Unenhanced CT images showed
      heterogeneous masses in four cases and a homogeneous mass in one case. One of the
      tumours showed some areas of calcification. T1-weighted MRI images showed
      isointense lesions. T2-weighted images showed mixed isointense and mild
      hyperintense lesions. All cases showed bone destruction and had infiltrated into
      the nasal fossa, orbit, infratemporal fossa, and other adjacent tissues. Seven
      cases showed mild to moderate heterogeneous enhancement on contrast-enhanced CT
      or T1-weighted MRI images. CONCLUSION: IMTs of the maxillary sinus can be
      characterized as a soft-tissue mass with bony destruction and infiltration of the
      adjacent tissues, with mild to moderate enhancement after the injection of
      contrast medium. CT and MRI can help to diagnose IMTs, determine the extent of
      the lesion and its relationship with adjacent tissues, and thus facilitate the
      prediction of surgical resectability.

PMID- 22974571
TI  - Impact of the H1N1 influenza pandemic in two rural emergency departments.
AB  - INTRODUCTION: The World Health Organization declared an influenza H1N1 global
      pandemic in June 2009, which resulted in a great deal of research. However, no
      studies have been published on incidence, characteristics and impact in rural
      emergency departments (EDs). METHODS: Data were gathered from two rural EDs
      located in Southwestern Ontario. A retrospective chart review was performed on
      all visits to the hospitals' EDs with ICD-10 codes relating to influenza-like
      illnesses (ILI). The chart review periods were 1 September 2009 to 1 January 2010
      for the H1N1 study group and 1 September 2008 to 1 January 2009 for the control
      group. RESULTS: There were 546 cases of ILI during the H1N1 pandemic period out
      of 8339 total ED visits (6.5%). This was a 4.1 fold increase from the previous
      year when 132 cases of ILI were identified out of 8125 ED visits (1.6%). Half the
      cases of ILI that presented during the H1N1 pandemic occurred in patients aged 1
      to 20 years, a proportion significantly larger during the pandemic compared with
      the control period. Time-to-physician assessment did increase significantly
      during the pandemic (41 min vs 52 min) without resulting in an increased mean
      length of stay in the ED (122 min vs 120 min). Using the Canadian Triage and
      Acuity Scale, a patient severity rating that dictates time to medical care, no
      differences in severity of ILI cases were observed. Nor were there no differences
      observed in discharge rates, admission rates, transfers to other facilities,
      unscheduled ED visits with 72 hours, or mortality during the two periods.
      CONCLUSIONS: There was a significant increase in the incidence of ILI at the two
      rural EDs during the H1N1 pandemic compared with the previous year without a
      corresponding increase in severity of illness.

PMID- 22974572
TI  - Racial disparity in fracture risk between white and nonwhite children in the
      United States.
AB  - OBJECTIVES: To examine risk factors for fracture in a racially diverse cohort of
      healthy children in the US. STUDY DESIGN: A total of 1470 healthy children, aged
      6-17 years, underwent yearly evaluations of height, weight, body mass index,
      skeletal age, sexual maturation, calcium intake, physical activity levels, and
      dual-energy x-ray absorptiometry (DXA) bone and fat measurements for up to 6
      years. Fracture information was obtained at each annual visit, and risk factors
      for fracture were examined using the time-dependent Cox proportional hazards
      model. RESULTS: The overall fracture incidence was 0.034 fracture per person-year
      with 212 children reporting a total of 257 fractures. Being white (hazard ratio
      [HR] = 2.1), being male (HR = 1.8), and having skeletal age of 10-14 years (HR =
      2.2) were the strongest risk factors for fracture (all P <= .001). Increased
      sports participation (HR = 1.4), lower body fat percentage (HR = 0.97), and
      previous fracture in white girls (HR = 2.1) were also significant risk factors
      (all P <= .04). Overall, fracture risk decreased with higher DXA z scores, except
      in white boys, who had increased fracture risk with higher DXA z scores (HR =
      1.7, P < .001). CONCLUSIONS: Boys and girls of European descent had double the
      fracture risk of children from other backgrounds, suggesting that the genetic
      predisposition to fractures seen in elderly adults also manifests in children.

PMID- 22974573
TI  - Enzyme replacement is associated with better cognitive outcomes after transplant
      in Hurler syndrome.
AB  - OBJECTIVE: To investigate whether intravenous enzyme replacement therapy (ERT)
      benefits cognitive function in patients with mucopolysaccharidosis type IH
      (Hurler syndrome) undergoing hematopoietic cell transplantation (HCT). STUDY
      DESIGN: Data were obtained for 9 children treated with HCT + ERT (ERT group) and
      10 children treated with HCT only (no-ERT group) from neuropsychologic
      evaluations before HCT and at 1-year and 2-year post-HCT follow-up. RESULTS: At 2
      years after HCT, children in the ERT group lost 9.19 fewer IQ points per year
      compared with children in the no-ERT group (P = .031). Furthermore, the ERT group
      improved in nonverbal problem solving and processing, whereas the no-ERT group
      declined, resulting in a difference of 9.44 points per year between the 2 groups
      (P < .001). CONCLUSION: ERT in association with HCT enhances cognitive outcomes,
      providing new evidence that ERT is a valuable addition to the standard
      transplantation protocol. Although the mechanism responsible for this improved
      outcome is unknown, both direct benefits and indirect effects must be considered.

PMID- 22974574
TI  - Nail-fold excision for the treatment of ingrown toenail in children.
AB  - OBJECTIVE: To evaluate the effectiveness of the nail-fold excision procedure in
      children. STUDY DESIGN: Prospectively collected data on patients less than 18
      years of age who underwent a nail-fold excision for symptomatic ingrown toenail
      were analyzed. Patients were seen in 2 centers and data collected included
      demographics, site of ingrown toenail, complications (including recurrence),
      patient satisfaction, and duration of follow-up. RESULTS: Overall, 67 procedures
      were performed on 50 patients between June 2009 and July 2011 at the 2
      institutions. The mean age was 14 years (range, 9-18 years) and 30 were male
      patients. No recurrences were seen after a follow-up for a median of 14 months
      (range 6-28 months). Patients were very satisfied with the cosmetic outcomes. Six
      minor complications occurred, including 3 patients with bleeding requiring
      dressing change, 2 with excessive granulation tissue, and 1 with nail growth
      abnormality. CONCLUSIONS: The nail-fold excision technique is highly effective in
      the pediatric population, with no recurrence, excellent cosmesis, and very high
      patient satisfaction.

PMID- 22974575
TI  - Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an
      undiagnosed growth disorder.
AB  - We present the case of a 19-year-old man with a growth disorder, which was
      undefined, despite extensive evaluation. Whole exome sequencing demonstrated a
      novel homozygous frameshift mutation in CUL7, one of the causative genes of 3-M
      syndrome. We discuss the utility of exome sequencing in diagnosing rare
      disorders.

PMID- 22974576
TI  - Maternal psychological stress after prenatal diagnosis of congenital heart
      disease.
AB  - OBJECTIVE: To determine whether prenatal diagnosis of congenital heart disease
      (CHD) increases maternal stress. STUDY DESIGN: Self-report instruments were
      administered to mothers carrying a fetus with CHD. Domains included: (1)
      traumatic stress (Impact of Events Scale-Revised); (2) depression (Beck
      Depression Index II); and (3) anxiety (State-Trait Anxiety Index). Modifiers
      included: (1) coping skills (COPE Inventory); (2) partner satisfaction (Dyadic
      Adjustment Scale); and (3) demographics. Multivariate linear regression models
      were used to assess relationships between stress measures and modifiers. RESULTS:
      Fifty-nine mothers (gestational age 27 +/- 3 weeks) completed all measures.
      Clinically important traumatic distress was seen in 39%, depression in 22%, and
      state anxiety in 31%. Lower partner satisfaction was associated with higher
      depression (P < .01) and higher anxiety (P < .01). After controlling for partner
      satisfaction and income, "denial" was most associated with increased traumatic
      stress, anxiety, and depression (P < .01). CONCLUSIONS: Posttraumatic stress,
      depression, and anxiety are common after prenatal diagnosis of CHD. Healthy
      partner relationships and positive coping mechanisms can act as buffers.

PMID- 22974577
TI  - Tonsillectomy variation in the United States: the evidence is catching up, but
      are the payers aware of the evidence?

PMID- 22974578
TI  - Pediatric osteoporosis: where are we now?

PMID- 22974579
TI  - Role of free school lunch in the associations between family-environmental
      factors and children's fruit and vegetable intake in four European countries.
AB  - OBJECTIVE: To determine whether an association exists between different clusters
      of fruit- and vegetable-specific family-environmental factors and children's
      daily fruit and vegetable intake, and whether these associations differ between
      countries with different school lunch policies. DESIGN: Cross-sectional data from
      four European countries participating in the Pro Greens project in 2009. These
      countries have different school food policies: two serve free school lunches and
      two do not. Self-administered data were used. Food frequency questions served to
      assess fruit and vegetable intakes. The study assessed sixteen children-perceived
      family-environmental factors, which were clustered based on principal component
      analysis into five sum variables: fruit and vegetable encouragement; vegetable
      modelling, family routine and demand; fruit modelling; fruit and vegetable
      snacking practices; and fruit and vegetable allowing. SETTING: Schools in
      Finland, Germany, Sweden and the Netherlands. SUBJECTS: Schoolchildren aged 11
      years (n 3317). RESULTS: Multilevel logistic regression analyses revealed
      positive associations between nearly all clustered family-environmental factors
      and daily fruit and vegetable intake. The study tested a moderation effect
      between family-environmental factors and school lunch policy. In five out of
      twenty models significant interactions occurred. In the stratified analyses, most
      of the associations between family-environmental factors and raw and cooked
      vegetable intake were stronger in Germany and the Netherlands, neither of which
      provided free school lunches. CONCLUSIONS: Children reporting more fruit- and
      vegetable-promoting family-environmental factors had a more frequent intake of
      fruits and vegetables; the associations were stronger for vegetable intakes in
      countries providing no free school lunches, suggesting that parental involvement
      is crucial when schools offer no vegetables.

PMID- 22974580
TI  - Anti-inflammatory effects of phlorofucofuroeckol B-rich ethyl acetate fraction
      obtained from Myagropsis myagroides on lipopolysaccharide-stimulated RAW 264.7
      cells and mouse edema.
AB  - Myagropsis myagroides has been used as a Chinese medicine and its extract has
      shown various biological activities, however, its anti-inflammatory mechanism
      remains unknown. In this study, we investigated the inhibitory effects of the
      ethyl acetate fraction of M. myagroides (EFM) on the production of inflammatory
      mediators and pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated
      RAW 264.7 cells. EFM significantly inhibited LPS-induced production of nitric
      oxide (NO), prostaglandin E(2), and pro-inflammatory cytokines in a dose
      dependent manner and suppressed the production of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 in RAW 264.7 cells. Inhibitory effect of EFM on iNOS
      expression and NO production was further confirmed using LPS-activated mouse
      peritoneal macrophages. EFM treatment strongly suppressed the activation of
      nuclear factor-kappa B (NF-kappaB) by suppressing phosphorylation of Akt and
      extracellular signal-regulated kinases (ERKs). EFM as well as phlorofucofuroeckol
      B (PFF-B), a major compound isolated from EFM, reduced ear edema induced by
      phorbol 12-myristate 13-acetate in mice. These results indicate that the anti
      inflammatory effect of EFM, rich in PFF-B, on LPS-stimulated macrophages is
      regulated by the inhibition of NF-kappaB pathway through the inhibition of ERKs
      and Akt phosphorylation in LPS-stimulated macrophage cells.

PMID- 22974581
TI  - The effects of (+/-)-Praeruptorin A on airway inflammation, remodeling and
      transforming growth factor-beta1/Smad signaling pathway in a murine model of
      allergic asthma.
AB  - (+/-)-Praeruptorin A (PA) is a pair of coumarin enantiomers isolated from the
      root of Peucedanum praeruptorum Dunn (PPD), a common Chinese herbal medicine for
      the treatment of asthma. Considering its anti-inflammatory, anti-contractile and
      anti-hyperplasia activities, the effects of PA on airway inflammation and airway
      remodeling were investigated using a murine model of chronic asthma. Ovalbumin
      sensitized BALB/c mice were challenged with ovalbumin to induce asthma every
      other day on eight successive weeks. PA was administered intragastrically before
      every ovalbumin challenge. Airway responsiveness was evaluated by a lung function
      analysis system 48 h after the last ovalbumin challenge. The total and
      differential leukocytes in bronchoalveolar lavage fluid (BALF) were counted using
      a hemocytometer and Diff-Quick-stained smears. Lung tissue samples were used for
      hematoxylin and eosin, periodic acid Schiff, Masson's trichrome and alpha-SMA
      immunohistochemistry staining. Levels of cytokines in BALF, immunoglobulin (Ig) E
      in serum as well as expression of TGF-beta1 and Smad proteins in lung tissue were
      measured by enzyme-linked immunosorbent assay, immunohistochemistry or western
      blot analysis. Compared with the model group, PA suppressed airway inflammation,
      airway hyperresponsive and remodeling, reduced levels of IL-4 and IL-13 in BALF,
      and IgE in serum, inhibited expression of TGF-beta1 and pSmad2/3, up-regulated
      the expression of Smad7 in lung tissue, and also increased the levels of INF
      gamma in BALF. These results suggested that PA significantly suppressed airway
      inflammation and airway remodeling induced by ovalbumin challenge, and is a
      potential candidate for the treatment of asthma.

PMID- 22974582
TI  - Multiparameter flow cytometry evaluation of plasma cell DNA content and
      proliferation in 595 transplant-eligible patients with myeloma included in the
      Spanish GEM2000 and GEM2005<65y trials.
AB  - The incorporation of high-dose therapy/autologous stem cell transplantation
      (HDT/ASCT) and novel agents has significantly improved survival in patients with
      multiple myeloma (MM), but whether this improvement also benefits patients
      harboring poor prognostic features, such as nonhyperdiploid MM (NH-MM) and a high
      proliferation index, remains largely unknown. We analyzed the DNA content and
      proliferation index of bone marrow plasma cells (PCs) by multiparameter flow
      cytometry in 595 newly diagnosed transplant-eligible patients with MM included in
      two consecutive PETHEMA/GEM trials: GEM2000 [VBMCP/VBAD (vincristine, carmustine,
      melphalan, cyclophosphamide, prednisone/vincristine, bischloroethylnitrosourea,
      adriamycin, and dexamethasone) followed by HDT/ASCT; n = 319] and GEM2005<65y
      (randomized induction with VBMCP/VBAD/bortezomib or thalidomide/dexamethasone or
      bortezomib/thalidomide/dexamethasone followed by HDT/ASCT; n = 276). Of the 595
      patients, 295 were classified as NH-MM (49.6%) and 336 (56.5%) as high
      proliferative MM (>=1% PCs in S-phase). Detection of NH-MM DNA content and >=1%
      PCs in S-phase were of independent prognostic value for overall survival.
      Treatment with bortezomib-based regimens abrogated the inferior overall survival
      of patients with >=1% PCs in S-phase but not of patients with NH-MM. Finally, a
      comparative analysis of PC proliferation index at diagnosis versus disease
      progression showed a twofold increase at relapse in 44 of 52 patients (85%)
      analyzed at both time points. NH-MM and a high proliferation index assessed by
      multiparameter flow cytometry remain as independent prognostic factors in MM, but
      the latter may be overcome by incorporating novel agents in the HDT/ASCT setting.

PMID- 22974584
TI  - Involvement of recepteur d'origine nantais receptor tyrosine kinase in Epstein
      Barr virus-associated nasopharyngeal carcinoma and its metastasis.
AB  - Nasopharyngeal carcinoma (NPC) is characteristic for its strong association with
      Epstein-Barr virus (EBV) and high metastatic rate. Recently, overexpressed
      recepteur d'origine nantais (RON) (MST1R), receptor tyrosine kinase has been
      reported in human cancers and tumor metastasis. Therefore, the role of RON in EBV
      associated NPC and its metastasis was investigated. Here we show that RON was
      found in NPC but not in control tissues. A significant correlation of latent
      membrane protein 1 (LMP1) and RON expression was found in NPC (Pearson's chi(2)
      test; P = 0.0023). At the molecular level, LMP1 stimulates nuclear factor-kappaB
      binding to the RON promoter through its carboxyl-terminal activation region 1 to
      induce expression of RON. Knockdown of RON in cells expressing LMP1 significantly
      reverses LMP1-induced epithelial-mesenchymal transition and suppresses LMP1
      induced cell migration and invasion. These results suggest an important role of
      RON in the tumorigenesis and metastasis of NPC and RON may be a novel therapeutic
      target for EBV-associated NPC.

PMID- 22974583
TI  - Nuclear Kaiso indicates aggressive prostate cancers and promotes migration and
      invasiveness of prostate cancer cells.
AB  - Kaiso, a p120 catenin-binding protein, is expressed in the cytoplasmic and
      nuclear compartments of cells; however, the biological consequences and clinical
      implications of a shift between these compartments have yet to be established.
      Herein, we report an enrichment of nuclear Kaiso expression in cells of primary
      and metastatic prostate tumors relative to the normal prostate epithelium.
      Nuclear expression of Kaiso correlates with Gleason score (P < 0.001) and tumor
      grade (P < 0.001). There is higher nuclear expression of Kaiso in primary
      tumor/normal matched samples and in primary tumors from African American men (P <
      0.0001). We further found that epidermal growth factor (EGF) receptor up
      regulates Kaiso at the RNA and protein levels in prostate cancer cell lines, but
      more interestingly causes a shift of cytoplasmic Kaiso to the nucleus that is
      reversed by the EGF receptor-specific kinase inhibitor, PD153035. In both DU-145
      and PC-3 prostate cancer cell lines, Kaiso inhibition (short hairpin RNA-Kaiso)
      decreased cell migration and invasion even in the presence of EGF. Further, Kaiso
      directly binds to the E-cadherin promoter, and inhibition of Kaiso in PC-3 cells
      results in increased E-cadherin expression, as well as re-establishment of cell
      cell contacts. In addition, Kaiso-depleted cells show more epithelial morphology
      and a reversal of the mesenchymal markers N-cadherin and fibronectin. Our
      findings establish a defined oncogenic role of Kaiso in promoting the progression
      of prostate cancer.

PMID- 22974585
TI  - Multivariate analysis of cell culture bioprocess data--lactate consumption as
      process indicator.
AB  - Multivariate analysis of cell culture bioprocess data has the potential of
      unveiling hidden process characteristics and providing new insights into factors
      affecting process performance. This study investigated the time-series data of
      134 process parameters acquired throughout the inoculum train and the production
      bioreactors of 243 runs at the Genentech's Vacaville manufacturing facility. Two
      multivariate methods, kernel-based support vector regression (SVR) and partial
      least square regression (PLSR), were used to predict the final antibody
      concentration and the final lactate concentration. Both product titer and the
      final lactate level were shown to be predicted accurately when data from the
      early stages of the production scale were employed. Using only process data from
      the inoculum train, the prediction accuracy of the final process outcome was
      lower; the results nevertheless suggested that the history of the culture may
      exert significant influence on the final process outcome. The parameters
      contributing most significantly to the prediction accuracy were related to
      lactate metabolism and cell viability in both the production scale and the
      inoculum train. Lactate consumption, which occurred rather independently of the
      residual glucose and lactate concentrations, was shown to be a prominent factor
      in determining the final outcome of production-scale cultures. The results
      suggest possible opportunities to intervene in metabolism, steering it towards
      the type with a strong propensity towards high productivity. Such intervention
      could occur in the inoculum stage or in the early stage of the production-scale
      reactors. Overall, this study presents pattern recognition as an important
      process analytical technology (PAT). Furthermore, the high correlation between
      lactate consumption and high productivity can provide a guide to apply quality by
      design (QbD) principles to enhance process robustness.

PMID- 22974586
TI  - The prevalence of Acarapis woodi in Spanish honey bee (Apis mellifera) colonies.
AB  - Acarapis woodi is an internal obligate parasite of the respiratory system of
      honey bees which provokes significant economic losses in many geographical areas.
      The main aim of this study was assess the A. woodi role in the "higher honey bee
      colony losses phenomenon" in Spain. Therefore, a new polymerase chain reaction
      (PCR) was developed to amplify the mitochondrial cytochrome oxidase I gene (COI)
      and so the actual prevalence of A. woodi in Spanish honey bee colonies in 2006
      and 2007 was determined as part of a wider survey. The results revealed a greater
      prevalence than expected in most of the geographical areas studied where has been
      generally underestimated One problem encountered in this study was to distinguish
      between A. woodi and other species (Acarapis dorsalis and Acarapis externus) at
      the molecular level. Furthermore, the patterns of genetic divergence across
      sequences raised serious doubts about the current classification of these
      organisms.

PMID- 22974588
TI  - Simple way of facilitating intraoral condylectomy and securing the excised
      condyle: technical note.

PMID- 22974589
TI  - Is the 3-D CT model useful to our anaesthetists?
AB  - A case report of a nasal spur detected on pre-operative 3-D Cad-Cam models
      illustrating the use of these models in predicting and preventing anaesthetic
      difficulties.

PMID- 22974587
TI  - CDPKs in immune and stress signaling.
AB  - Ca(2+) has long been recognized as a conserved second messenger and principal
      mediator in plant immune and stress responses. How Ca(2+) signals are sensed and
      relayed into diverse primary and global signaling events is still largely
      unknown. Comprehensive analyses of the plant-specific multigene family of Ca(2+)
      dependent protein kinases (CDPKs) are unraveling the molecular, cellular and
      genetic mechanisms of Ca(2+) signaling. CDPKs, which exhibit overlapping and
      distinct expression patterns, sub-cellular localizations, substrate specificities
      and Ca(2+) sensitivities, play versatile roles in the activation and repression
      of enzymes, channels and transcription factors. Here, we review the recent
      advances on the multifaceted functions of CDPKs in the complex immune and stress
      signaling networks, including oxidative burst, stomatal movements, hormonal
      signaling and gene regulation.

PMID- 22974590
TI  - Cortisol levels in children with attention-deficit/hyperactivity disorder.
AB  - Regulation of the Hypothalamus-Pituitary-Adrenal axis (HPA-axis) and its end
      product cortisol differs among persons with certain psychiatric disorders when
      compared with controls. Some reports concern Attention-Deficit/Hyperactivity
      Disorder (ADHD) but findings are inconclusive. In this study we collected four
      saliva samples during a regular weekday in children, 6-17 years old, with ADHD (n
      = 201) and non-affected comparisons (n = 221). Saliva cortisol was measured with
      radioimmunoassay technique. Clinical data were collected for diagnostic
      information. Subtypes and severity of symptoms were determined using parental
      rating scales. Children with ADHD had lower saliva cortisol levels than
      comparisons at waking up Median = 9.1 versus 12.7 nmol/L (p < .001), 30 min later
      Median = 15.8 versus 20.1 nmol/L (p < .001) and before going to bed Median = 0.8
      versus 1.0 nmol/L (p = .015). No difference was found for the afternoon sample.
      When the study group was split into three different age groups similar results
      were found only for children above 10 years of age. Subtype of ADHD or co
      occurring symptoms did not affect the cortisol levels. Degree of severity of ADHD
      symptoms was not associated with cortisol levels in the study group, other than a
      weak negative correlation between the afternoon sample and hyperactivity
      symptoms. The low cortisol levels in children with ADHD may indicate a
      dysregulation of the HPA-axis, for instance a down-regulation or a phase delay of
      the diurnal curve. The low levels may be related to the under-arousal possibly
      underlying several of the core symptoms of ADHD.

PMID- 22974591
TI  - Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis
      and schizophrenia in relapse.
AB  - Schizophrenia is chronic and debilitating mental disorder. In broad spectrum of
      possible causes or contributing factors, immune system and cytokines were
      investigated in the onset and development of schizophrenia. The aim of our study
      was to analyze the serum concentrations of type-1 cytokines: TNF-alpha, IFN
      gamma, type-2 cytokines: IL-4, IL-10, type-17 cytokine: IL-17 and regulatory
      cytokines: TGF-beta, IL-27, IL-6, in drug-naive patients with First Episode
      Psychosis - FEP (n = 88) and Schizophrenia in relapse - SC in relapse patients (n
      = 45), comparing to healthy controls (n = 36). Also, we attempted to determine
      potential correlation between cytokine levels and/or cytokine ratios with
      clinical parameters, such as severity of illness, positive, negative and general
      psychopathology. Our results showed decreased levels of IL-17 (p = 0.018),
      demonstrating that type-17 response is blunted in psychotic episode. Increased
      levels of IL-4 (p = 0.033) showed that type-2 response is overweight in psychotic
      episode. Also, levels of IL-4 in serum of SC in relapse patients were higher than
      controls (p < 0.0005) and patient with FEP (p = 0.003). This alteration was
      accompanied with increase in production of TGF-beta in psychotic patients (p =
      0.009) and also in FEP (p < 0.0005) and SC in relapse (p < 0.0005). Analysis
      showed that TGF-beta can be a valuable marker for psychosis. The presence of
      enhanced anti-inflammatory/immunosuppressive activity in schizophrenia may be an
      attempt to counteract or limit ongoing pro-inflammatory processes and
      downregulating chronic inflammation. Finally we have documented decreased levels
      of IL-17 and IL-17/TGF-beta ratio in these types of psychotic patients,
      suggesting the new aspects of schizophrenia pathophysiology.

PMID- 22974593
TI  - Families and patients as actors in simulation: adding unique perspectives to
      enhance nursing education.

PMID- 22974592
TI  - Quantification of type II procollagen splice forms using alternative transcript
      qPCR (AT-qPCR).
AB  - During skeletal development, the onset of chondrogenic differentiation is marked
      by expression of the alpha1(II) procollagen (Col2a1) gene. Exon 2 of Col2a1 codes
      for a cysteine-rich von Willebrand factor C-like domain. Chondroprogenitors
      express the exon 2-containing IIA and IID splice forms by utilizing adjacent 5'
      splice sites separated by 3 base pairs. There is a shift to expression of the
      shorter, exon 2-lacking IIB splice form with further differentiation. Alternative
      splicing analysis of Col2a1 splice forms has often relied upon semi-quantitative
      PCR, using a single set of PCR primers to amplify multiple splice forms. We show
      that this widely used method is inaccurate due to mismatched amplification
      efficiency of different-sized PCR products. We have developed the TaqMan(r)-based
      AT-qPCR (Alternative Transcript-qPCR) assay to more accurately quantify
      alternatively spliced mRNA, and demonstrate the measurement of Col2a1 splice form
      expression in differentiating ATDC5 cells in vitro, and in wild type mouse
      embryonic and postnatal cartilage in vivo. The AT-qPCR assay is based on the use
      of a multiple-amplicon standard (MAS) plasmid, containing a chemically
      synthesized cluster of splice site-spanning PCR amplicons, to quantify
      alternative splice forms by standard curve-based qPCR. The MAS plasmid designed
      for Col2a1 also contained an 18S rRNA amplicon for sample normalization, and an
      amplicon corresponding to a region spanning exon 52-53 to measure total Col2a1
      mRNA. In mouse E12.5 to P70 cartilages, we observed the expected switch between
      the IIA and IIB splice forms; no IID or IIC splice products were observed.
      However, in the ATDC5 cultures, predominant expression of the IIA and IID splice
      forms was found at all times in culture. Additionally, we observed that the sum
      of the IIA, IIB and IID splice forms comprises only a small fraction of Col2a1
      transcripts containing the constitutive exon 52-53 junction. We conclude from our
      results that the majority of ATDC5 cells in the assay described in this study
      remained as chondroprogenitors during culture in standard differentiation
      conditions, and that additional Col2a1 transcripts may be present. The validity
      of this novel AT-qPCR assay was confirmed by demonstrating the expected Col2a1
      isoform expression patterns in vivo in developing mouse cartilage. The ability to
      measure true levels of procollagen type II splice forms will provide better
      monitoring of chondrocyte differentiation in other model systems. In addition,
      the AT-qPCR assay described here could be applied to any gene of interest to
      detect and quantify known and predicted alternative splice forms and can be
      scaled up for high throughput assays.

PMID- 22974594
TI  - A greenprint for sustainable contraceptive research and development.

PMID- 22974595
TI  - Postabortion family planning counseling and services for women in low-income
      countries: a systematic review.
AB  - BACKGROUND: Unsafe abortion imposes heavy burdens on both individuals and
      society, particularly in low-income countries, many of which have restrictive
      abortion laws. Providing family planning counseling and services to women
      following an abortion has emerged as a key strategy to address this issue. STUDY
      DESIGN: This systematic review gathered, appraised and synthesized recent
      research evidence on the effects of postabortion family planning counseling and
      services on women in low-income countries. RESULTS: Of the 2965 potentially
      relevant records that were identified and screened, 15 studies satisfied the
      inclusion criteria. None provided evidence on the effectiveness of postabortion
      family planning counseling and services on maternal morbidity and mortality. One
      controlled study found that, compared to the group of nonbeneficiaries, women who
      received postabortion family planning counseling and services had significantly
      fewer unplanned pregnancies and fewer repeat abortions during the 12-month follow
      up period. All 15 studies examined contraception-related outcomes. In the seven
      studies which used a comparative design, there was greater acceptance and/or use
      of modern contraceptives in women who had received postabortion family planning
      counseling and services relative to the no-program group. CONCLUSIONS: The
      current evidence on the use of postabortion family planning counseling and
      services in low-income countries to address the problem of unsafe abortion is
      inconclusive. Nevertheless, the increase in acceptance and/or use of
      contraceptives is encouraging and has the potential to be further explored.
      Adequate funding to support robust research in this area of reproductive health
      is urgently needed.

PMID- 22974596
TI  - Small bowel obstruction and perforation after Essure sterilization: a case
      report.
AB  - BACKGROUND: We present a rare but serious complication of Essure microinsert
      sterilization. STUDY DESIGN: Case report. RESULTS: A 42-year-old woman presented
      with nausea, vomiting, abdominal pain and abdominal distension 1 month after
      uncomplicated Essure sterilization. Abdominal X-ray showed small bowel
      obstruction. At subsequent laparotomy, a stretched Essure device was found
      ensnaring the terminal ileum. It had caused strangulation and local perforation
      of the bowel wall. The device was removed and an ileocecal resection with side-to
      side ileocolostomy was performed. In retrospect, the aberrant location of the
      right Essure device near the ileocecal junction was noticed on the abdominal X
      ray. CONCLUSIONS: This case illustrates that perforation of an Essure device can
      result in a serious complication leading to ileocecal resection. An abdominal X
      ray with specific attention to the correct location of the Essure coils is
      advisable for patients presenting with small bowel obstruction after Essure
      sterilization.

PMID- 22974597
TI  - [Neurological complications in patients receiving solid organ transplants].
AB  - INTRODUCTION: Neurological complications (NC) are a significant cause of
      morbidity and mortality in paediatric patients receiving solid organ transplants.
      Our aim was to describe the experience of our hospital with NC in paediatric
      patients receiving heart, lung and liver transplants. PATIENTS AND METHODS: A
      retrospective study was conducted on 140 paediatric patients who received a solid
      organ transplant during the period 2000-2011. RESULTS: A total of 23 paediatric
      solid organ transplant recipients (16.4% of cases), with a median age of 6 years,
      had NC. The symptoms were, in order of frequency: acute symptomatic seizures (12
      patients); acute encephalopathy (11 patients); neuromuscular weakness (4
      children), tremor (4 children), headache (2 children), neuropathic pain (2
      children), and visual disturbances (2 children). The aetiologies of NC were: the
      neurotoxicity of the immunosuppressive drugs (12 patients), post-hypoxic
      ischaemic encephalopathy (6 patients), infections (2 cases), mechanical
      compression of peripheral nerve during surgery (2 cases), and a metabolic
      complication (1 case). The five patients who met the criteria of posterior
      reversible encephalopathy syndrome had a favourable outcome. Seven patients died,
      four of them due to hypoxic-ischaemic encephalopathy. CONCLUSIONS: NC are common
      in paediatric patients receiving heart, liver, lung, and renal transplants, with
      acute symptomatic seizures and acute encephalopathy being the most common
      clinical signs. No differences were found in the NC with the different types of
      transplants. Neurotoxicity of the immunosuppressive drugs and hypoxic-ischaemic
      encephalopathy were the main causes of NC, having different management and
      outcomes. The prognosis was favourable in most of the patients, except for those
      who had moderate or severe post-hypoxic-ischaemic damage.

PMID- 22974598
TI  - Patterns of surgical weight loss and resolution of metabolic abnormalities in
      superobese bariatric adolescents.
AB  - PURPOSE: The aim of the study was to compare the baseline and the 18-month follow
      up for weight and metabolic characteristics of superobese (SO) (body mass index
      [BMI] >=50 kg/m(2)) and morbidly obese (MO) (BMI <50 kg/m(2)) adolescents who
      participated in a prospective longitudinal study of gastric banding delivered in
      an adolescent multidisciplinary treatment program. METHODS: Clinical information
      was extracted from an institutional review board-approved database of bariatric
      adolescents. Fasting cytokine and acute phase protein serum levels were analyzed
      by enzyme-linked immunosorbent assay. Liver histopathologies were assessed using
      the Kleiner's classification score. RESULTS: Other than BMI, MO (n = 11) and SO
      (n = 7) patients have similar degree of insulin resistance, dyslipidemia, and
      nonalcoholic fatty liver disease. Serum C-reactive protein (10.2 +/- 5.6 SO vs 4
      +/- 3.9 MUg/mL MO [P < .02]) and leptin (71 +/- 31 SO vs 45 +/- 28 MO ng/mL [P =
      .04]) were more elevated in SO patients. Although weight loss is similar (30 +/-
      19 kg MO vs 28 +/- 12 kg SO, P = .8 at 18 months; mean percent change in BMI,
      22.8% +/- 11.6% vs 20.5% +/- 10.3% SO, P = .2), SO patients has less resolution
      of insulin resistance and dyslipidemia but experienced significantly improved
      health-related quality of life. CONCLUSIONS: The SO adolescents demonstrate
      equivalent short-term weight loss and improved quality of life but delayed
      metabolic response to a gastric banding-based weight loss treatment program
      compared with MO patients, illustrating the importance of early referral for
      timely intervention of MO patients.

PMID- 22974599
TI  - Noninvasive measurement of fecal calprotectin and serum amyloid A combined with
      intestinal fatty acid-binding protein in necrotizing enterocolitis.
AB  - BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature
      infants, remains challenging. Enterocyte damage in NEC can be assessed by
      intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a
      specificity of 90%. Numerous markers of inflammation are known, such as serum
      amyloid A (SAA) and fecal calprotectin. PURPOSE: The aim of the present study was
      to evaluate which combination of noninvasive measurement of inflammatory markers
      and I-FABP improves the diagnostic accuracy in neonates suspected for NEC.
      METHODS: In 62 neonates with clinical suspicion of NEC (29 with final diagnosis
      of NEC), urinary I-FABP, urinary SAA, and fecal calprotectin levels were
      determined quantitatively. Diagnostic accuracy was calculated for the
      combinations I-FABP-SAA and I-FABP-fecal calprotectin, using a multivariable
      logistic regression model. RESULTS: The combination of SAA and I-FABP did not
      increase the diagnostic accuracy of I-FABP. However, the combination of fecal
      calprotectin and I-FABP improved accuracy significantly. The combination of
      urinary I-FABP and fecal calprotectin measurement produced a sensitivity of 94%,
      a specificity of 79%, a positive likelihood ratio of 4.48, and a negative
      likelihood ratio of 0.08. CONCLUSION: The combination of noninvasive measurement
      of I-FABP and fecal calprotectin seems promising for diagnosing NEC at an early
      time point. Prospective analysis is required to confirm this finding and to
      evaluate better treatment strategies based on noninvasive measurement of I-FABP
      and calprotectin.

PMID- 22974600
TI  - Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage
      in experimental necrotizing enterocolitis.
AB  - BACKGROUND/PURPOSE: Necrotizing enterocolitis (NEC) represents one of the gravest
      complications in premature infants and carries significant morbidity and
      mortality. There is a great need for improved diagnostic methods to reduce the
      severity and incidence of NEC. The aim of the study was to investigate if
      intraluminal microdialysis can detect intestinal ischemia in newborn rats with
      induced experimental NEC. METHODS: The studies were performed on 1-day-old
      Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation
      treatment. Microdialysis catheters were rectally inserted and placed in the
      rectosigmoid part of the colon. Microdialysate levels of glucose, lactate,
      pyruvate, and glycerol were measured. Intestinal specimens were collected at the
      end of the experiments for microscopic evaluation. RESULTS: Intraluminal
      microdialysis revealed signs of intestinal hypoxia and cellular damage, with a
      marked increase of lactate and glycerol. Microscopic evaluation confirmed
      intestinal damage in the NEC group. CONCLUSION: Intraluminal microdialysis can
      detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model
      of NEC. Intestinal intraluminal microdialysis is easily accessible through the
      rectum and may be a useful noninvasive complement to other methods in the
      assessment of NEC.

PMID- 22974601
TI  - Antioxidant effects of N-acetylcysteine in a neonatal rat model of necrotizing
      enterocolitis.
AB  - BACKGROUND/PURPOSE: Hypoxia and ischemia appear to play an important role in the
      pathogenesis of necrotizing enterocolitis (NEC), which may be related to oxygen
      derived free radical formation. This study was designed to evaluate the role of
      oxidative stress and potentially beneficial effects of N-acetylcysteine (NAC) in
      a neonatal rat model of NEC. METHODS: Thirty Wistar albino rat pups were randomly
      divided into 3 groups: group 1, control; group 2, NEC and saline; and group 3,
      NEC and NAC treatment. Necrotizing enterocolitis was induced by hyperosmolar
      enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C
      and oxygen. The pups were killed on the fourth day, and their intestinal tissues
      were harvested for biochemical and histopathologic analysis. RESULTS: Mucosal
      injury scores and intestinal malondialdehyde levels in group 2 were found to be
      significantly higher than that in other groups (P <= .05). Intestinal superoxide
      dismutase activities in group 3 were significantly higher than that in group 2 (P
      = .018). Intestinal tissue tumor necrosis factor alpha levels were significantly
      reduced with NAC treatment in group 3 compared with group 2 (P < .003).
      CONCLUSIONS: It is likely that oxidative stress and inflammatory mediators
      contribute to the pathogenesis of NEC and that NAC has a protective effect on
      intestinal injury through its antiinflammatory and antioxidant properties.

PMID- 22974602
TI  - Colonic conduit for esophageal replacement: long-term endoscopic and
      histopathologic changes in colonic mucosa.
AB  - BACKGROUND: Long-term follow-up has substantiated the colon as a durable and
      highly acceptable esophageal substitute. Exposure of colonic conduit to gastric
      acid may lead to histopathologic changes in the form of chronic inflammation.
      MATERIALS/METHODS: Thirty children with esophageal replacement were studied from
      2 to 12 years (mean, 5.20 years) postoperatively. All cases underwent upper
      gastrointestinal tract endoscopy to evaluate the gross appearance of colonic
      conduit mucosa, and punch biopsies were taken from upper and lower junctions of
      the conduit. All biopsies were submitted to histopathologic examination. RESULTS:
      Endoscopic findings were comparable with normal regarding the gross appearance of
      colonic mucosa in both upper and lower junctions (25 cases/83.3%). Some
      abnormalities were seen including cervical anastomosis stricture (2 cases/6.7%),
      redundancy (3 cases/10%), mucosal ulcer in the lower residual esophagus (1
      case/3.3%), and hyperemia (3 cases/10%). Pathologic changes were minimal
      regarding the change in position of the colon to a thoracic organ during follow
      up. Most of the cases were normal (22 cases/73.3%). Seven cases (23.4%) showed
      mild chronic nonspecific inflammation of the colonic mucosa, whereas only 1 case
      (3.3%) showed mildly active inflammation of colonic mucosa. CONCLUSION: The use
      of the colon for esophageal replacement showed that no significant pathologic
      changes affecting its function as a conduit because its mucosa showed no
      significant change in response to gastric acid reflux in long-term follow-up and
      can be further protected by an antireflux procedure.

PMID- 22974603
TI  - The surgical approach for cervicothoracic masses in children.
AB  - BACKGROUND: The surgical approach to masses located in the cervicothoracic
      juncton represents a challenge for surgeons. Many techniques have been described
      with good results. METHODS: We analyzed and compared the results obtained in 2
      Italian pediatric surgery centers using 2 different techniques in patients with
      tumors of the thoracic inlet: center 1, using anterior cervical transsternal
      approach on 7 patients, and center 2, applying "trap-door" technique on 5
      patients. RESULTS: Excision was incomplete in 5 patients and complete in 7
      patients. Histologic examination revealed 5 patients with neuroblastoma; 3,
      ganglioneuroblastoma; 1, mixoid liposarcoma; 1, desmoid fibromatosis; 1,
      Castleman disease; and 1, Schwann cell tumor. The median duration of the
      procedure was 345 minutes in center 1 and 245 minutes in center 2. The median
      blood loss was 200 mL in both centers. The median hospital stay was 11 days in
      center 1 and 9 days in center 2. Globally, 5 patients developed postoperative
      complications. No significant differences were encountered comparing the main
      surgical outcome parameters between the 2 approaches. CONCLUSIONS: Both
      techniques resulted in valid options to achieve a safe excision of thoracic inlet
      masses with a manageable complication rate and acceptable hospital stay. Surgical
      risk factors should be carefully investigated preoperatively. Postoperative pain
      control is important to guarantee early recovery.

PMID- 22974604
TI  - The effect of curcumin on lung injuries in a rat model induced by aspirating
      gastrointestinal decontamination agents.
AB  - BACKGROUND: Aspiration is one of the most feared complications of
      gastrointestinal decontamination procedures with nonabsorbed polyethylene glycol
      (PEG) solution and activated charcoal (AC). We aimed to investigate the
      protective effects of curcumin (CUR) on lung injury in rats induced by aspiration
      of these agents. METHODS: Experimental rats were divided randomly into 6 groups
      (n = 7): a saline-aspirated control (group I), sterile saline aspirated with CUR
      treatment (group II), PEG aspirated (group III), PEG aspirated with CUR treatment
      (group IV), AC aspirated (group V), and AC aspirated with CUR treatment (group
      VI). After aspiration, treatment groups II, IV, and VI were given 150 mg/kg CUR
      intraperitoneally once a day for 7 days. After 7 days, the rats were humanely
      killed, and both the lungs and serum specimens from all groups were evaluated
      histopathologically, immunohistochemically, and biochemically. RESULTS:
      Aspiration of gastrointestinal decontamination agents produced histopathologic
      changes, elevated levels of malondialdehyde and surfactant protein D, reduced
      levels of antioxidant enzymes, and increased expression of inflammatory cytokines
      interleukin-1beta and tumor necrosis factor alpha. Curcumin treatments
      effectively attenuated the rats' pulmonary inflammation responses (as shown by
      reduced alveolar damage), decreased serum malondialdehyde and surfactant protein
      D levels, and inhibited the expressions of tumor necrosis factor alpha and
      interleukin-1beta. CONCLUSIONS: Because of its anti-inflammatory effects, CUR
      treatment may have preventive effects on lung injuries induced by aspirating
      gastrointestinal decontamination agents.

PMID- 22974605
TI  - Repair of pediatric bladder rupture improves survival: results from the National
      Trauma Data Bank.
AB  - BACKGROUND/PURPOSE: The urinary bladder is the second most commonly injured
      genitourinary organ. The objective of this study was to describe the management
      of pediatric traumatic bladder ruptures in the United States and their
      association with surgical repair and mortality. METHODS: We searched the 2002
      2008 National Trauma Data Bank for all pediatric (<18 years old) subjects with
      bladder rupture. Demographics, mechanism of injury, coexisting injury severity,
      and operative interventions for bladder and other abdominal trauma are described.
      Multivariate logistic regression analysis was used to examine the relationship
      between bladder rupture and both bladder surgery and in-hospital mortality.
      RESULTS: We identified 816 children who sustained bladder trauma. Forty-four
      percent underwent bladder surgery, including 17% with an intraperitoneal injury.
      Eighteen percent had ?2 intra-abdominal injuries, and 40% underwent surgery to
      other abdominal organs. In multivariate analysis, operative bladder repair
      reduced the likelihood of in-hospital mortality by 82%. A greater likelihood of
      dying was seen among the uninsured and those with more severe injuries and
      multiple abdominal injuries. CONCLUSIONS: After bladder trauma, pediatric
      patients demonstrate significantly improved survival when the bladder is
      surgically repaired. With only 67% of intraperitoneal bladder injuries being
      repaired, there appears to be underuse of a life-saving procedure.

PMID- 22974606
TI  - The significance of detrusor wall thickness as a prognostic factor in pediatric
      bladder outlet obstruction.
AB  - PURPOSE: The purpose of this study is to determine detrusor thickness as a
      prognostic factor in posterior urethral valves. METHODS: The medical information
      of 41 patients diagnosed with posterior urethral valves at our institute was
      retrospectively reviewed. The serum creatinine level after bladder decompression,
      results of ultrasonography, and voiding cystourethrography were compared between
      groups divided according to the final bladder and renal function. Detrusor
      thickness was measured using Muller's method. RESULTS: The median detrusor
      thickness was 1.3 mm (0.4-2.5 mm). After median 45.6 months (7.2-96.0 months) of
      follow-up, impaired bladder function (IBF) was observed in 14 patients. In
      multivariate analysis, detrusor thickness greater than 1.3 mm (odds ratio, 32.6;
      95% confidence interval, 3.1-340.6; P = .004) was the only independent risk
      factor for later IBF. Final renal function impairment developed in 24 patients
      (58.5%), and 3 patients (7.3%) were diagnosed with end-stage renal disease after
      median 66.0 months (32.4-133.2 months) of follow-up period. On multivariate
      analysis, age-specific elevated serum creatinine level at presentation (odds
      ratio, 11.1; 95% confidence interval, 1.1-112.5; P = .042) was an independent
      risk factor. CONCLUSIONS: Detrusor thickness more than 1.3 mm on ultrasonography
      was an independent prognostic factor for later IBF.

PMID- 22974607
TI  - Comparison of femoral and carotid blood pressure during laparoscopy in piglets.
AB  - PURPOSE: The impact of a capnoperitoneum on the known blood pressure (BP)
      difference of the upper and lower limb was studied in piglets. METHODS: Eleven
      German Landrace piglets (body weight, 4.3-7.4 kg; mean body weight, 6.2 kg) were
      studied. Arterial lines were placed in the right carotid and right femoral artery
      for pressure monitoring. Intraabdominal pressure levels were increased in steps
      of 6 mm Hg up to 24 mm Hg. RESULTS: We found that elevated intraabdominal
      pressures up to 24 mm Hg did not change the preexisting systolic BP difference
      between the carotid and femoral arteries. Systolic femoral artery pressure
      constantly remained 5% higher than its carotid counterpart. In addition, mean and
      diastolic values were not affected. CONCLUSIONS: Arterial BP measurements
      recorded at the legs of piglets when abdominal pressure is increased by up to 24
      mm Hg can be used for intraoperative assessment of systemic arterial BP.

PMID- 22974608
TI  - Aberrant high expression of NRG1 gene in Hirschsprung disease.
AB  - BACKGROUND/PURPOSE: Hirschsprung disease (HSCR) is a congenital disorder
      characterized by the absence of intramural ganglion cells along with variable
      lengths of the gastrointestinal tract. Recent studies have indicated the
      potential function of neuregulin-1 (NRG1) in HSCR, which encodes the heregulins
      and other mitogenic ligands for the ErbB family. The purpose of this study was to
      further clarify the role of NRG1 in the pathogenesis of HSCR. METHODS: We
      examined the NRG1 messenger RNA (messenger RNA) and protein expression levels in
      gut tissues of 63 patients with sporadic HSCR (both stenotic and dilated gut
      tissues) and 35 controls. Moreover, using the methylation-specific polymerase
      chain reaction, we examined the methylation pattern of exon 1 of the NRG1 gene.
      RESULTS: The mRNA expression levels of NRG1 were significantly higher in tissues
      of HSCR than those in controls, and the increased NRG1 protein levels in HSCR
      were consistent with the mRNA levels. However, no methylation pattern change was
      observed in exon 1 of the gene among different groups. CONCLUSIONS: Our study
      demonstrates that the aberrant expression of NRG1 may play an important role in
      the pathology of HSCR. DNA methylation of the gene seems not to be involved in
      the mechanism of such aberrant expression, and other factors should be explored.

PMID- 22974609
TI  - RET 3'UTR polymorphisms and its protective role in Hirschsprung disease in
      southeastern Chinese.
AB  - BACKGROUND: Hirschsprung disease (HSCR) is a complex congenital disorder
      characterized by intestinal obstructions owing to the absence of the intestinal
      ganglion cells of the nerve plexuses in variable lengths of the digestive tract.
      Several RET polymorphisms and haplotypes have been described as underrepresented
      in HSCR patients with respect to controls. We thus sought to investigate whether
      polymorphisms in RET 3'UTR are associated with isolated HSCR in the Chinese
      population. METHODS: Polymerase chain reaction amplification and direct
      sequencing were used to screen polymorphisms in RET 3'UTR in patients with
      sporadic HSCR and ethnically matched controls in Han Chinese populations.
      Association tests of RET 3'UTR variants and haplotypes with HSCR were performed.
      RESULTS: We examined a total of 107 Chinese sporadic HSCR patients and 89
      ethnically matched controls by sequencing the 3'UTR of the RET gene. Five single
      nucleotide polymorphisms (SNPs) and 2 monomorphic SNPs were identified. The
      genotype distributions and the allele frequencies of the 5 SNPs were
      significantly different between HSCR cases and controls and occurred more
      frequently in the control population. Haplotype analysis has shown a higher
      frequency of haplotypes comprising variant alleles in controls as compared with
      cases. CONCLUSIONS: The significant deviations of the genotype distributions and
      the allele frequencies of these SNPs in the HSCR population compared with the
      control population demonstrate that these SNPs have a strong negative association
      with HSCR and could act as protective alleles.

PMID- 22974610
TI  - Do open repair and different laparoscopic techniques in pediatric inguinal hernia
      repairs affect the vascularization of testes?
AB  - PURPOSE: The aim of this study was to evaluate, using Doppler ultrasonography,
      the effects of different hernia repair techniques on testicular perfusion in the
      pediatric age group. METHODS: This study was based on a prospective clinical
      trial of 72 pediatric patients over 2 years of age with unilateral inguinal
      hernia. They were operated on using 1 of 3 different techniques. Group 1 included
      26 patients who were treated with a conventional open hernia repair technique.
      Group 2 included 22 patients who underwent Schier intracorporeal laparoscopic
      suture technique. Group 3 included 24 patients who underwent the laparoscopic
      partial excision and purse-string technique described by Montupet. In all cases,
      blood flow index of the centripetal and capsular arteries of the testes,
      including peak systolic velocity (PSV) and resistivity index (RI), were examined
      by using Doppler ultrasound preoperatively and early and late postoperatively.
      RESULT: The conventional open technique group (group 1) had transient temporary
      changes in PSV and RI values compared with preoperative findings; however, these
      changes were not statistically significant. No such changes were observed in the
      2 laparoscopic groups. CONCLUSION: Neither conventional open nor laparoscopic
      hernia repair techniques impaired testes vascularization. Surgical manipulations
      performed using the conventional open repair technique caused transient, but not
      significant, changes in PSV and RI values.

PMID- 22974611
TI  - One third of patients with a unilateral palpable undescended testis have a
      contralateral patent processus.
AB  - PURPOSE: The purpose of this study was to determine the incidence and predictive
      factors associated with a contralateral patent processus vaginalis in boys with a
      unilateral palpable undescended testis. METHODS: We retrospectively reviewed the
      records of 77 consecutive boys (median age, 15 months; range, 5 months to 17.7
      years) who had undergone orchiopexy for a unilateral palpable testis. At inguinal
      orchiopexy, an 8F feeding tube and a 70 degrees  adult cystoscope lens were
      placed into the peritoneum through the hernia sac, and the contralateral internal
      ring was inspected. The clinical factors that might predict the presence of a
      contralateral patent processus vaginalis were determined. RESULTS: The overall
      rate of a contralateral patent processus vaginalis was 34% in those with a
      significant ipsilateral hernia sac. After considering age, side, prematurity,
      location, and volume of the undescended testis, only the boys with a testis
      distal to the external ring compared with those with testes lying within the
      inguinal canal had statistically increased odds of a patent contralateral
      processus vaginalis (odds ratio, 3.1; 95% confidence interval, 1.08-9.08).
      CONCLUSION: Approximately one third of boys with a unilateral palpable
      undescended testis will have a contralateral patent processus vaginalis as
      determined by transinguinal laparoscopy. The rate is higher (52%) if the
      undescended testis was distal to the external ring. Both the etiology and
      significance of this contralateral finding are unknown.

PMID- 22974612
TI  - Comparison of the protective effect of dipyridamole and acetylsalicylic acid on
      long-term histologic damage in a rat model of testicular ischemia-reperfusion
      injury.
AB  - PURPOSE: Ischemia reperfusion injury arising from testicular torsion results in a
      loss of spermatogenesis and a significant increase in germ cell apoptosis. We
      investigated the effects of dipyridamole and acetylsalicylic acid (ASA), 2 well
      known platelet inhibitors, on testicular ischemia reperfusion injury. METHODS:
      Thirty adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6
      for each group): control, sham-operated, torsion/detorsion (T/D), T/D +
      dipyridamole, and T/D + ASA. Testicular ischemia was achieved by rotating the
      left testis 720 degrees  clockwise for 2 hours. Thirty minutes before torsion, 10
      mg/kg dipyridamole was injected transperitoneally in the T/D + dipyridamole
      group, and 100 mg/kg ASA was injected transperitoneally in the T/D + ASA group.
      Sixty days after the initial surgical procedure, ipsilateral orchiectomies were
      performed for histopathologic examination to determine Johnsen's mean testicular
      biopsy score (MTBS), mean seminiferous tubular diameter (MSTD), and apoptotic
      index (AI) in all groups. RESULTS: Unilateral testicular torsion-detorsion led to
      a significant decrease in Johnsen's MTBS and MSTD values in the ipsilateral
      testis and a significant increase in AI values of the T/D group. There were no
      significant differences between the T/D + dipyridamole and control groups in
      terms of MSTD and MTBS values. Although an amount of improvement exits in T/D +
      ASA group, there were significant differences between the T/D + ASA and control
      group MSTD and MTBS values. There was no significant difference between the T/D +
      dipyridamole and control groups in terms of AI values (P > .05), but the
      differences between the T/D + ASA and control groups were significant despite a
      slight decline in AI values of the T/D + ASA group. CONCLUSIONS: Our findings
      show that the use of dipyridamole before testicular reperfusion has a potentially
      protective effect against long-term injury in testicular ischemia reperfusion
      injury.

PMID- 22974613
TI  - Is matrix metalloproteinase required in postnatal testicular tubules for germ
      cell maturation?
AB  - BACKGROUND/AIM: Cryptorchidism may cause infertility by failed transformation of
      neonatal gonocytes into adult dark spermatogonia, the putative stem cells for
      spermatogenesis. Gonocytes migrate centrifugally to the tubular basement membrane
      to become adult dark spermatogonia. Regulation of this transformation remains
      unknown. We aimed to investigate neonatal rodent testis matrix metalloproteinase
      (MMP) production to see whether MMPs loosen extracellular matrix between Sertoli
      cells to facilitate gonocyte movement. METHODS: Sprague-Dawley rat testes (n = 4
      6 per group) were collected at embryonic day 19 (E19) and postnatal (P) days P0
      to 10 for immunohistochemistry. Immunofluorescent confocal images were captured
      for presence of membrane type 1 MMP (MT1-MMP), matrix metalloproteinase 2 (MMP2),
      tissue inhibitor of metalloproteinase 2 (TIMP2), mouse VASA homologue, anti
      Mullerian hormone, and androgen receptor in tissue sections. Testicular proteins
      were analyzed by immunoblotting. RESULTS: Membrane type 1 MMP was strongly
      present in gonocytes at E19 then decreased, whereas it increased in testicular
      somatic cells from P0 to P10. Testicular protein levels of MT1-MMP, MMP2, and
      androgen receptor were constant from E19 to P10. Anti-Mullerian hormone protein
      sharply decreased after P2, whereas TIMP2 gradually increased from E19 to P10.
      Gonocytes migrated to basement membrane at P2 to P6. CONCLUSION: Membrane type 1
      MMP, MMP2, and TIMP2 were present in testis from E19 to P10 during gonocyte
      migration and transformation into spermatogenic stem cells. Increased knowledge
      about germ cell development may aid efforts to improve fertility in
      cryptorchidism.

PMID- 22974614
TI  - Protective effect of intraperitoneal ozone application in experimental ovarian
      ischemia/reperfusion injury.
AB  - AIM: The current accepted management of ovarian torsion is ovary-sparing surgery.
      Ozone therapy is used to reduce ischemia/reperfusion (I/R) injury in several
      situations. An experimental study was designed to evaluate effect of ozone
      application in ovarian I/R injury. MATERIALS AND METHODS: Three groups (n = 6)
      and 18 rats were included in the study. After anesthesia, right ovaries were
      fixed and removed at the end of 2 hours in sham group (SG). In torsion group
      (TG), right ovaries underwent 720 degrees  torsion in a counterclockwise
      direction. Ovaries were removed after 2 hours torsion and 2 hours reperfusion. In
      ozone group (OG), torsion was created by the same technique, and 95% oxygen plus
      5% ozone gas mixture was given intraperitoneally (25 MUg/mL, 0.5 mg/kg) 10
      minutes before reperfusion. After 2 hours reperfusion, ovaries were removed.
      Histopathologic examination of ovarian and periovarian sections was performed for
      the presence of congestion (C), hemorrhage, interstitial edema (IE), and
      polymorphonuclear neutrophilic infiltrations. Tissue samples were analyzed for
      malondialdehyde, nitric oxide (NO), and total sulphidryl (t-SH) values. Results
      were compared between 3 groups. RESULTS: At histopathologic examination, the TG
      have elevation in terms of ovarian C, polymorphonuclear neutrophilic
      infiltration, and periovarian IE when compared with SG (P < ,05). In OG, ovarian
      C and periovarian IE were reduced according to TG, whereas the increase was
      observed only in ovarian C compared with SG (P < .05). At biochemical evaluation
      of oxidative stress markers in SG and TG, there was no difference between them (P
      < .05). Malondialdehyde levels were significantly lower in OG than TG, whereas NO
      and t-SH values were higher (P < .05). Malondialdehyde levels were decreased in
      OG compared with SG (P < .05). However, no difference was observed in NO and t-SH
      levels (P > .05). CONCLUSION: Intraperitoneal application of ozone creates a
      positive impact on histologic and biochemical markers on I/R injury owing to
      ovarian torsion. The ozone application can be developed to support efforts to
      protect ovary in ovarian torsion.

PMID- 22974615
TI  - Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary
      model: biochemical and histopathologic evaluation.
AB  - BACKGROUND/PURPOSE: The aim of the study was to evaluate the effects of selenium
      (Se) on ischemia/reperfusion (I/R) injury in rat ovaries. METHODS: Thirty-five
      female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S),
      I/R1, I/R2, Se1, and Se2. In the I/R1 and Se1 groups, 4 hours of ischemia was
      followed by 6 hours of reperfusion, and in the I/R2 and Se2 groups, 4 hours of
      ischemia was followed by 12 hours of reperfusion. In the Se groups, 30 minutes
      before reperfusion, a single dose of 0.2 mg/kg Se was administered
      intraperitoneally. The ovarian tissue levels of malondialdehyde (MDA) and nitric
      oxide (NO), and the activities of superoxide dismutase (SOD), catalase (CAT), and
      glutathione peroxidase (GPx) were measured biochemically. Tissue damage to
      ovarian tissue was scored by histopathologic examination. RESULTS: The I/R groups
      had significantly higher MDA levels and lower CAT, SOD, and GPx activities than
      the sham group (P < .05). Although NO levels were significantly higher in the
      I/R1 group than in the sham group (P < .05), the NO levels in the I/R2 and sham
      groups were similar. Selenium pretreatment significantly lowered tissue MDA and
      NO levels and increased tissue SOD and GPx activities in the Se groups, compared
      with those in the I/R groups (P < .05). Catalase activities were significantly
      higher in the Se2 group than in the I/R2 group (P < .05). Catalase activities
      were higher in the Se1 group than in the I/R1 group, but the difference was not
      statistically significant. Treatment with Se significantly decreased the ovarian
      tissue damage scores in the Se2 group compared with those in the I/R2 group (P <
      .05). CONCLUSION: Selenium is effective in preventing tissue damage induced by
      I/R in rat ovaries.

PMID- 22974616
TI  - Percutaneous central venous catheterization through the external jugular vein in
      children: is inserting the guide wire into the superior vena cava essential for
      successful catheterization?
AB  - BACKGROUND/PURPOSE: The external jugular vein (EJV) is an attractive alternative
      for percutaneous central venous catheterization (PCVC), with fewer complications.
      The inability to pass the guide wire into the superior vena cava (SVC) is,
      however, a major reason for the failure of this approach. The authors report a
      modification of the Seldinger technique to increase the effectiveness of this
      procedure in children. METHODS: Between May 2008 and June 2009, we performed 100
      PCVCs consecutively in children using the Seldinger technique through the EJV
      (Step 1). In cases in which the guide wire could not be passed into the SVC, the
      guide wire was kept in the EJV; and only the catheter was introduced into the
      central venous position (Step 2). Differences between the standard and modified
      Seldinger techniques were analyzed. RESULTS: The procedure with the standard
      Seldinger technique (Step 1) was successful in 13 (13%) out of 100 patients. In
      84 (96.5%) of the 87 remaining patients, PCVC was achieved with the modified
      Seldinger technique, without the insertion of the guide wire until the SVC (Step
      2). Altogether, 97 catheters (97%) were successfully inserted, with 85 (87.6%)
      correctly positioned in the SVC. In addition, there were 7 (7%) clinically
      irrelevant hematomas during catheterization. CONCLUSIONS: The EJV is an excellent
      alternative anatomical location for the completion of PCVC in children. Placing
      the guide wire in a central position is not essential to the success rate of this
      approach. The proposed modified Seldinger technique allowed PCVC to be performed
      through the EJV safely and with a high success rate in children and adolescents.

PMID- 22974618
TI  - Management of rectal pyogenic granuloma with transanal mucosal sleeve resection.
AB  - In children, pyogenic granulomas are most commonly cutaneous benign vascular
      lesions but can also present in the gastrointestinal tract. When they occur in
      the intestine, they can cause acute or chronic gastrointestinal bleeding. We
      present an unusual case of rectal pyogenic granuloma and our management strategy.

PMID- 22974617
TI  - Enterocyte expression of epidermal growth factor receptor is not required for
      intestinal adaptation in response to massive small bowel resection.
AB  - PURPOSE: Intestinal adaptation after massive small bowel resection (SBR) permits
      improved absorption of enteral nutrition despite significant loss of bowel
      length. Epidermal growth factor (EGF) and its receptor (EGFR) have previously
      been established to play major roles in the pathogenesis of adaptation. This
      study tested the hypothesis that EGFR signaling within the epithelial cell
      compartment (enterocytes) is required for intestinal adaptation. METHODS: We
      developed a tamoxifen-inducible Villin-Cre/LoxP recombinant system for enterocyte
      directed EGFR deletion using EGFR-floxed mice. Epidermal growth factor receptor
      null mice and wild-type littermates underwent either 50% proximal SBR or sham
      operation. Ileal tissue was harvested on postoperative day 7. To assess for
      adaptation, villus height and crypt depth as well as rates of crypt cell
      proliferation and apoptosis were measured. RESULTS: Adaptation after SBR occurred
      normally, as demonstrated by significant increases in villus height, crypt depth,
      and crypt proliferative and apoptotic index in both the wild-type and EGFR-null
      mice. CONCLUSION: Enterocyte EGFR expression is not required for the adaptation
      response to massive SBR. This novel finding suggests that enterocyte
      proliferation during adaptation is regulated by EGFR signaling in cells other
      than enterocytes, perhaps within the mesenchymal cell compartment of the bowel
      wall via factor(s) that are presently unknown.

PMID- 22974619
TI  - Conservative management of spontaneous bile duct perforation in infancy:: case
      report and literature review.
AB  - Spontaneous bile duct perforation in infants is rare, with less than 150 cases
      having been reported worldwide. With a highly variable presentation, diagnosis
      and treatment can prove challenging, and outcomes are not without significant
      morbidity. We herewith report the case of an 8-week-old male infant with
      spontaneous bile duct perforation. He initially presented with abdominal sepsis
      and septated ascites on ultrasound, which was confirmed as bilious on ascitic tap
      and at diagnostic laparoscopy. Intraoperative cholangiogram demonstrated a
      localized leak at the junction of the cystic and common bile duct. Conversion to
      laparotomy was ultimately required with cholecystostomy, and 2 external
      intraabdominal drains were placed. He was subsequently managed conservatively
      with 4 weeks external drainage, with a repeat cholangiogram at 6 weeks,
      demonstrating successful resolution of the leak. The reported case supports the
      findings of changing practices in the existing literature. We suggest that, in
      cases of spontaneous bile duct perforation with no distal obstruction, dissection
      and surgery to the biliary tree are not always required. Conservative management
      with simple external drainage can have its complications but, as shown here, can
      be a successful treatment option in terms of healing of perforation.

PMID- 22974620
TI  - Pseudotumerous enlargement of the umbilical cord owing to an intra-amniotic
      varicosity associated with thrombocytopenia.
AB  - Herein, we describe a male infant with an antenatally diagnosed single umbilical
      artery and extensive varicosities of the umbilical vein with tumor-like
      appearances. Consumption coagulopathy occurred postnatally, and surgical
      resection of the umbilical cord led to a normalization of the platelet count.

PMID- 22974621
TI  - Myositis ossificans requires multiple diagnostic modalities.
AB  - Myositis ossificans is a type of bone-forming lesion that arises in soft tissue
      and mimics malignancy. We present a case of myositis ossificans in a 16-year-old
      girl with anxiety disorder, Asperger syndrome, and no known history of trauma. A
      variety of diagnostic tools including magnetic resonance, ultrasound, and biopsy
      are used to make the diagnosis. The histologic and radiographic findings used to
      distinguish this disorder from malignant conditions are discussed.

PMID- 22974622
TI  - A simple technique of oblique anastomosis can prevent stricture formation in
      primary repair of esophageal atresia.
AB  - BACKGROUND: Anastomotic stricture is an important problem after esophageal
      atresia (EA) repair. This study evaluates a technique of oblique esophageal
      anastomosis without use of a flap in order to prevent stricture formation.
      METHODS: Medical records of 16 patients (14 with EA type III and 2 with EA type
      IV Ladd-Gross classification) who underwent primary repair of EA at birth without
      anastomotic tension were reviewed, evaluating long-term follow-up results. All
      patients were studied with esophageal contrast study, pH-multichannel
      intraluminal impedance, and endoscopy. The incidence of complications and their
      management were analysed. RESULTS: Contrast esophagogram and esophagoscopy always
      showed regular patency of the suture line. CONCLUSIONS: Our technique of oblique
      anastomosis is simple, safe, and effective in preventing stricture formation even
      in the long-term follow-up.

PMID- 22974623
TI  - Laparoscopic port-in-cyst technique for retrieval of hepatic hydatid and review
      of other techniques used in literature.
AB  - AIM: To describe a technique used for removal of hepatic hydatid cyst
      laparoscopically. PATIENTS AND METHODS: The removal of hydatid membranes was
      achieved by inserting a 10-mm port right above the cyst. The port is made to
      enter the cyst, and the membranes are removed without any contact to outer
      surface, thus avoiding peritoneal spillage. RESULTS: The technique was used in 6
      patients. Mean age was 3.5 years, range being. 2.5 to 6 years. Three patients had
      solitary cyst in the right lobe, and 2, in left lobe. One had multiple cyst
      involving both right and left lobes. Follow-up is of mean 6 months. There is no
      recurrence or evidence of new cyst owing to peritoneal seeding. CONCLUSIONS: Safe
      extraction of hydatid membranes during laparoscopy can be done by directly
      placing the port within the decompressed cyst and removing the membranes with
      minimal use of suction. The port-in-cyst technique excludes any possibility of
      peritoneal seeding, during hydatid removal which may lead to metachronous
      recurrence in the peritoneum.

PMID- 22974624
TI  - Impressive achievements of a 2009 humanitarian mission by the US Naval Ship
      Comfort.

PMID- 22974625
TI  - Are Baveno V recommendations of any help in the management of extrahepatic portal
      hypertension in Latin America?

PMID- 22974626
TI  - Tension pneumoperitoneum in a child.

PMID- 22974628
TI  - Extraskeletal Ewing sarcoma of the mesocolon in a child.
AB  - Ewing sarcoma (ES) is a malignant neoplasm usually affecting the skeletal system.
      Extraskeletal ES is a rare tumor. To date, only 1 case of primary mesocolon ES
      has been previously reported in an adult. Herein, we present the first case of ES
      in the mesocolon in a child.

PMID- 22974629
TI  - Two different flaps for reconstruction of gunshot wounds to the foot and ankle in
      a child.
AB  - An 8-year-old boy was shot in his right foot and ankle, which resulted in soft
      tissue lesions of the medial malleolus and lateral calcaneus, fracture of the
      medial malleolus, and partial loss of the calcaneus. We designed a distally based
      sural flap and a posterior tibial perforator flap for reconstruction of soft
      tissue defects at the lateral aspect of the calcaneus and the medial malleolus,
      respectively. Both flaps survived successfully, and the boy had a normal gait
      during follow-up.

PMID- 22974630
TI  - An unusual case of small bowel obstruction in a child caused by ingestion of
      water-storing gel beads.
AB  - Foreign body ingestion occurs most commonly in the pediatric population. Small
      bowel obstruction is a rare complication that can occur, and surgical
      intervention is required. We present the first report of a case of an 18-month
      old child with a jejunal obstruction caused by ingestion of water-storing gel
      beads used for botanical arrangements. The child presented with obstipation and
      nonbloody, nonbilious emesis. Symptoms resolved after a large bead 3 cm in
      diameter was retrieved via laparoscopic-assisted excision. This case suggests
      that water-storing gel beads are particularly dangerous foreign bodies and should
      be kept out of the reach of children.

PMID- 22974631
TI  - Percutaneous revascularization of reoccluded meso-Rex shunts in extrahepatic
      portal vein obstruction.
AB  - Extrahepatic portal vein (PV) obstruction (EHPVO) is a rare disorder in early
      childhood with unknown incidence and mostly unknown etiology. In children with
      EHPVO, the hepatopedal flow of the mesenteric venous blood is hindered by an
      obstruction of the PV resulting in prehepatic portal hypertension. The curative
      treatment with a meso-Rex shunt connects the superior mesenteric vein to the left
      PV by a venous autograft. Despite good primary patency, reocclusion of a meso-Rex
      bypass and its treatment can be challenging. We present 2 patients with EHPVO
      with subtotal functional occlusion of a meso-Rex shunt treated by percutaneous
      interventions with short- and mid-term follow-up.

PMID- 22974632
TI  - Dopamine-secreting adrenal ganglioneuroma in a child: beware of intraoperative
      rebound hypertension.
AB  - Ganglioneuromas are benign tumors originating from the neural crest and are
      composed of mature ganglion cells. We describe a 15-year-old normotensive
      adolescent girl with a 2-month history of left flank pain. Imaging revealed a
      left suprarenal mass with elevated urinary dopamine level. During laparoscopic
      adrenalectomy, intraoperative rebound hypertension occurred. After resection,
      dopamine levels normalized. The pathologic diagnosis revealed an adrenal
      ganglioneuroma.

PMID- 22974633
TI  - Diverticulitis in a child with Williams syndrome: a case report and review of the
      literature.
AB  - Diverticulitis is rare in pediatric patients and often associated with a more
      complicated course than that seen with adult patients. Certain syndromes, such as
      Williams syndrome, have been associated with an increase incidence of
      diverticular disease. We describe a 9-year-old boy with Williams syndrome who
      presented with rectal bleeding secondary to sigmoid diverticulitis. This case
      represents the youngest known patient with diverticulitis. Patients with this
      disorder who present with chronic or recurrent abdominal pain should be evaluated
      for diverticular disease and its potential complications.

PMID- 22974634
TI  - Failure of sclerotherapy in the treatment of thyroglossal duct cyst in children:
      2 case reports and review of the literature.
AB  - Thyroglossal duct cyst (TGDC) is one of most common congenital diseases of the
      midline of the neck. Most TGDC cases require treatment in the cases of cosmetic
      problems or recurrent infection, and a Sistrunk operation is considered to be the
      standard treatment. However, less invasive treatments are sometimes used, and
      sclerotherapy with OK-432 or ethanol is one such method. However, the validity or
      use of sclerotherapy as a TGDC treatment is controversial because cases of TGDC
      that have been successfully treated with sclerotherapy are rare, and the follow
      up period is short, and there are no statistical reports about the reoccurrence
      of symptoms after sclerotherapy. In this report, we review 2 recurrent TGDC cases
      after sclerotherapy with OK-432 and ethanol and discuss the efficacy and
      limitations of sclerotherapy.

PMID- 22974635
TI  - Successful tracheobronchial reconstruction of communicating bronchopulmonary
      foregut malformation and long segment congenital tracheal stenosis: a case
      report.
AB  - Communicating bronchopulmonary foregut malformation (CBPFM) and congenital
      tracheal stenosis (CTS) are difficult developmental disorders especially when
      they are presented simultaneously in a patient. The authors report a case of a
      newborn boy born at 37 weeks of gestation weighing 2356 g with CBPFM (right
      esophageal lung) and long segment CTS. Staged surgical repair (by-force
      endotracheal intubation for securing the airway followed by bronchotracheal
      anastomosis for CBPFM, tracheostomy with handmade, length-adjustable tracheostomy
      tube, and slide tracheoplasty) was performed. He has been healthy without
      tracheostomy for 25 months after slide tracheoplasty. This is the first report of
      a successful tracheobronchial reconstruction for a patient with a long segment
      CTS and CBPFM preserving the affected lung function.

PMID- 22974636
TI  - Treatment of chest wall osteosarcoma presenting as second primary after treatment
      of neuroblastoma.
AB  - Only 2 cases of osteosarcoma as a second primary malignancy after neuroblastoma
      have been reported in the literature. We present a case of chest wall
      osteosarcoma that developed in a 14-year-old boy 7 years after completion of
      chemotherapy, autologous peripheral blood stem cell transplantation, radiation,
      and resection for stage 3, high-risk neuroblastoma. A biopsy of a painful chest
      wall mass arising from the right third rib diagnosed osteosarcoma. He went on to
      have preoperative chemotherapy followed by wide local excision and chest wall
      reconstruction. He then received additional chemotherapy. This case highlights
      the importance of close observation for second malignancies in this patient
      population.

PMID- 22974637
TI  - Penetrating fetal trauma with late complications: a case report.
AB  - Survival after direct penetrating trauma to a fetus is very unusual. Our case
      below illustrates nonoperative management of a penetrating thoracoabdominal
      gunshot injury to the retroperitoneum with a late complication arising 15 years
      after the initial incident.

PMID- 22974638
TI  - ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a
      cytoprotective pathway.
AB  - Abro1 (Abraxas brother 1), also known as KIAA0157, is a scaffold protein that
      recruits various polypeptides to assemble the BRISC (BRCC36 isopeptide)
      deubiquitinating enzyme (DUB) complex. The BRISC enzyme has a Lys63-linked
      deubiquitinating activity and is comprised of four known subunits: MERIT40
      (mediator of Rap80 interactions and targeting 40kDa), BRE (brain and reproductive
      organ-expressed), BRCC36 (BRCA1/BRCA2-containing complex, subunit 3) and Abro1.
      We have previously shown that Abro1 has a cytoprotective role that involves the
      BRISC DUB complex acting on specific Lys63-linked polyubiquitinated substrates.
      In this report we identify three members of the AP-1 (activating protein-1)
      family, the ATF4, ATF5 (activating transcription factor) and JunD proteins, as
      specific interactors of Abro1. The function of ATF4-Abro1 interaction was
      investigated under normal conditions as well as under cellular stress. Abro1 is
      predominantly cytoplasmic, but during cellular stress it enters the nucleus and
      co-localizes with ATF4. Furthermore, this interaction with ATF4 is necessary and
      essential for the cytoprotective function of Abro1 following oxidative stress.
      The ability of Abro1 to specifically interact with a number of transcription
      factors suggests a new mechanism of regulation of the BRISC DUB complex. This
      regulation involves the participation of at least three known members of the AP-1
      family of transcription factors.

PMID- 22974639
TI  - Diacylglycerol kinase delta1 transiently translocates to the plasma membrane in
      response to high glucose.
AB  - The type II diacylglycerol kinases (DGKs) contain several functional domains such
      as a pleckstrin homology (PH) domain, two C1 domains and a sterile alpha-motif
      (SAM) domain. It was previously revealed that DGKdelta contributes to
      hyperglycemia-induced peripheral insulin resistance and thereby exacerbate the
      severity of type 2 diabetes. Moreover, a high extracellular concentration of
      glucose activated DGKdelta in skeletal muscle cells, which was followed by a
      reduction in the intracellular diacylglycerol levels and the inactivation of
      protein kinase Calpha, the enzyme that phosphorylates and inactivates the insulin
      receptor. However, the intracellular behavior of DGKdelta upon high glucose
      stimulation remains unclear. In this study, we found that DGKdelta1, but not a
      splice variant DGKdelta2 or the other type II DGKeta1/2, translocated from the
      cytoplasm to the plasma membrane in human embryonic kidney HEK293 and mouse
      myoblast C2C12 cells within 5 min in response to high glucose levels. The
      translocation was inhibited by phosphatidylinositol 3-kinase inhibitors, LY294002
      and GDC-0941, suggesting that the event is regulated via the phosphatidylinositol
      3-kinase pathway. Moreover, we revealed that the PH and C1 domains are
      responsible for the plasma membrane translocation and that the SAM domain
      negatively regulates the translocation. These results indicate that DGKdelta1 is
      the sole type II DGK isoform that responds rapidly and dynamically to high
      glucose levels.

PMID- 22974640
TI  - Basic neuroanatomy and stroke syndromes.
AB  - Stroke should not solely be considered a disease of the elderly, and racial
      disparities are most evident among young adults. Acute stroke can present at any
      age and it is important to be familiar with the evaluation and treatment of
      stroke to provide timely care. The National Institute of Health Stroke Scale
      helps physicians objectively evaluate stroke patients. This article presents an
      overview of basic information on neuroanatomy, pathophysiology, and stroke
      syndromes.

PMID- 22974641
TI  - Prehospital diagnosis and management of patients with acute stroke.
AB  - Significant advances in the early management of ischemic stroke have been made
      since the 1995 National Institute of Neurologic Disorders and Stroke data
      demonstrated the benefit of early intravenous administration of tissue
      plasminogen activator to select patients with acute ischemic stroke within a 3
      hour onset window of suspected stroke symptoms. One concept in stroke care that
      has become better understood is the importance of time management and the ability
      to deliver patients with acute stroke to appropriate care as soon as possible.
      Minimizing delay to definitive therapy remains the current focus in the
      prehospital phase of stroke care.

PMID- 22974642
TI  - Recognition and initial management of acute ischemic stroke.
AB  - This article addresses the recognition and management of acute ischemic stroke.
      It includes a discussion of cerebrovascular anatomy, common ischemic stroke
      syndromes, and central venous thrombosis. Extensive attention is paid to the
      initial emergency department management of stroke, addressing medical and systems
      issues, and treatment of ischemic stroke by thrombolysis.

PMID- 22974643
TI  - Neuroimaging in acute stroke.
AB  - This article reviews the various imaging modalities available for the evaluation
      of patients presenting with a potential stroke syndrome, specifically acute
      ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. It
      reviews the various computed tomography (CT) modalities, including noncontrast
      brain CT (NCCT), CT angiography, and CT perfusion. It discusses multimodal
      magnetic resonance imaging in the evaluation of patients with acute stroke,
      including diffusion-weighted imaging, T2-weighted sequences/fluid-attenuated
      inversion recovery, magnetic resonance angiography, perfusion-weighted imaging,
      and gradient-recalled echo. At the end of this article, a brief review on how to
      read an NCCT geared toward the emergency physician is included.

PMID- 22974644
TI  - Vertigo, vertebrobasilar disease, and posterior circulation ischemic stroke.
AB  - Dizzy patients present a significant diagnostic challenge to the emergency
      clinician. The discrimination between peripheral and central causes is important
      and will inform subsequent diagnostic evaluation and treatment. Isolated vertigo
      can be the only initial symptom of a posterior circulation stroke. The sensation
      of imbalance especially raises this possibility. Research involving strokes of
      the posterior circulation has lagged behind that of the anterior cerebral
      circulation. Investigations of the last 20 years, using new technologies in brain
      imaging in combination with detailed clinical studies, have revolutionized our
      understanding of the clinical presentation, causes, treatments, and prognosis of
      posterior circulation ischemia.

PMID- 22974645
TI  - Endovascular and neurosurgical management of acute ischemic stroke.
AB  - Acute ischemic stroke is recognized as the third leading cause of death in the
      United States; improved treatments for management are important to reduce
      disability and death. The standard of care of acute stroke therapy has been
      reperfusion/recanalization of the occluded vessels using pharmacologic
      management, endovascular management, or a combination approach. Significant
      improvements have been made in the management with the use of endovascular
      therapy. This article reviews the literature on the endovascular and
      neurosurgical management of patients presenting with acute ischemic stroke and
      presents current evidence-based guidelines for endovascular or neurosurgical
      interventions outlined for management of ischemic stroke.

PMID- 22974646
TI  - Intensive care management of acute ischemic stroke.
AB  - Despite the success of acute reperfusion therapies for the treatment of acute
      ischemic stroke, only a minority of patients receive such treatment. Even
      patients who receive reperfusion therapy remain at risk for further neuronal
      death through progressive infarction and secondary injury mechanisms. The goal of
      neurocritical care for the patient with acute ischemic stroke is to optimize long
      term outcomes by minimizing the amount of brain tissue that is lost to these
      processes. This is accomplished by optimizing brain perfusion, limiting secondary
      brain injury, and compensating for associated dysfunction in other organ systems.
      Because of the rapid and irreversible nature of ischemic brain injury, it is
      crucial for best neurocritical care practices to begin as early as possible.
      Therefore, this chapter will discuss optimal, pragmatic neurocritical care
      management of patients with acute ischemic stroke during the "golden" emergency
      department hours from the perspective of the neurointensivist. Major topics
      include cerebral perfusion optimization; management of cerebral edema; post
      thrombolytic care; acute anticoagulation; treatment of commonly associated
      cardiac and pulmonary complications; fluid, electrolyte and glucose management;
      the role of induced normothermia and therapeutic hypothermia; and prophylaxis
      against common complications.

PMID- 22974647
TI  - Transient ischemic attack: reviewing the evolution of the definition, diagnosis,
      risk stratification, and management for the emergency physician.
AB  - A transient ischemic attack (TIA) is an episode of reversible neurologic deficit
      caused by temporary focal central nervous system hypoperfusion. TIA is a medical
      emergency. Because patients with TIA in the emergency department (ED) have a high
      risk for stroke within the next 48 hours, it is imperative for the clinician to
      recognize this golden opportunity to prevent a disabling stroke. This article
      reviews our conceptual understanding of TIA, its definition, diagnosis, ways to
      stratify stroke risk, the acute management and disposition in the ED, and the
      potential future role of diagnostic biomarkers.

PMID- 22974649
TI  - Stroke mimics.
AB  - Stroke mimics are an important consideration for emergency physicians and
      physician extenders working in emergency departments. The emergency medicine
      physician must determine whether the acute neurologic deficits represent a
      transient event or a potential stroke. This article describes the common stroke
      mimic presentations by cause, including toxic-metabolic pathologies, seizure
      disorders, degenerative neurologic conditions, and peripheral neuropathies.

PMID- 22974650
TI  - Pediatric stroke.
AB  - Stroke is rare in children but leads to significant morbidity and mortality.
      Emergency department physicians are likely to be the first to evaluate children
      suffering strokes and it is, therefore, important for them to recognize common
      presenting features and risk factors for pediatric stroke. This review describes
      the epidemiology, clinical presentations, stroke types, associated risk factors,
      evaluation, treatment, and prognosis of pediatric stroke. Further research is
      needed on the acute and preventative treatments of pediatric stroke because
      merely applying our knowledge of stroke in adults to children is insufficient.

PMID- 22974651
TI  - Acute ischemic stroke. Foreward.

PMID- 22974652
TI  - Acute ischemic stroke. Preface.

PMID- 22974648
TI  - Intracranial hemorrhage.
AB  - Intracranial hemorrhage refers to any bleeding within the intracranial vault,
      including the brain parenchyma and surrounding meningeal spaces. This article
      focuses on the acute diagnosis and management of primary nontraumatic
      intracerebral hemorrhage and subarachnoid hemorrhage in the emergency department.

PMID- 22974653
TI  - Physiological and psychosocial age-related changes associated with reduced food
      intake in older persons.
AB  - Dietary intake changes during the course of aging. Normally an increase in food
      intake is observed around 55 years of age, which is followed by a reduction in
      food intake in individuals over 65 years of age. This reduction in dietary intake
      results in lowered levels of body fat and body weight, a phenomenon known as
      anorexia of aging. Anorexia of aging has a variety of consequences, including a
      decline in functional status, impaired muscle function, decreased bone mass,
      micronutrient deficiencies, reduced cognitive functions, increased hospital
      admission and even premature death. Several changes during lifetime have been
      implicated to play a role in the reduction in food intake and the development of
      anorexia of aging. These changes are both physiological, involving peripheral
      hormones, senses and central brain regulation and non-physiological, with
      differences in psychological and social factors. In the present review, we will
      focus on age-related changes in physiological and especially non-physiological
      factors, that play a role in the age-related changes in food intake and in the
      etiology of anorexia of aging. At the end we conclude with suggestions for future
      nutritional research to gain greater understanding of the development of anorexia
      of aging which could lead to earlier detection and better prevention.

PMID- 22974654
TI  - A comparison of the efficacy of transplantation of bone marrow-derived
      mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute
      myocardial infarction.
AB  - INTRODUCTION: A number of questions remain unanswered in the field of cell
      therapy for acute myocardial infarction, including what is the optimal cell type,
      and can therapeutic efficacy be enhanced by conditioning regimens. In this study,
      we sought to address these questions by directly comparing the effect of bone
      marrow-derived mesenchymal stem cells and unrestricted somatic stem cells
      delivered 24 hours post-myocardial infarction and by determining if the
      therapeutic efficacy of unrestricted somatic stem cells could be enhanced by
      exposing the cells to guiding factors before cell transplantation. METHODS:
      Unrestricted somatic stem cells were guided by exposure to 50 ng/mL basic
      fibroblast growth factor, 20 ng/mL hepatocyte growth factor and 20 ng/mL bone
      morphogenetic protein-2 for 24 hours. Using a Sprague-Dawley rat model of acute
      myocardial infarction, we transplanted cells by intramyocardial injection 24
      hours post-myocardial infarction. Cardiac function was serially measured using
      echocardiography, and histological analyses of infarct morphology, angiogenesis
      and apoptosis were obtained. Transcriptomic and proteomic changes were assessed
      using microarray and real-time quantitative PCR. RESULTS: When assessed 28 days
      after the myocardial infarction, the delivery of mesenchymal stem cells 24 hours
      post-myocardial infarction did not improve ejection fraction (P = 0.19), and did
      not prevent the decline in ejection fraction observed in the absence of cell
      therapy (P = 0.17). The administration of unrestricted somatic stem cells also
      did not improve ejection fraction (P = 0.11), but did prevent a further decline
      in ejection fraction (P = 0.001). Delivery of guided unrestricted somatic stem
      cells significantly improved ejection fraction (P = 0.03). Guided unrestricted
      somatic stem cells restored function to a greater extent than mesenchymal stem
      cells (P = 0.03). The infarct area (P = 0.2), apoptosis (P = 0.07) and
      angiogenesis (P = 0.09) did not differ between groups. Microarray analysis
      revealed that, following pre-implantation guiding, the gene groupings of mitosis,
      signalling and angiogenesis were highly overrepresented, mediators of apoptosis
      were overrepresented, and cardiomyocyte-associated genes were not differentially
      expressed. CONCLUSIONS: These results suggest that guided unrestricted somatic
      stem cells have a moderate capacity to repair cardiac damage and that they are
      more effective than mesenchymal stem cells in restoring cardiac function after a
      myocardial infarction. The mechanism of the benefit was not fully elucidated in
      this study, but these observations may be mediated by favorable dysregulation of
      angiogenic and apoptotic gene groupings.

PMID- 22974655
TI  - TransFix(r) for delayed flow cytometry of endothelial progenitor cells and
      angiogenic T cells.
AB  - Endothelial progenitor cells (EPC) and angiogenic T cells have not been validated
      for use in studies that involve delayed sample processing and analysis. Here, we
      report our results for the flow cytometric enumeration of circulating EPC and
      angiogenic T cells using TransFix(r)-treated whole blood obtained from adult
      patients with cardiovascular disease and healthy volunteers. Both cell types
      promote neovascularization and vascular homeostasis. As such they have been put
      forward as novel diagnostic markers for endothelial dysfunction and may add
      prognostic information in patients with cardiovascular disease. Our findings
      indicate that by the addition of TransFix(r) cellular antigen stabilizing reagent
      to whole blood, analyses can be postponed up to 7 days after blood collection.
      Therefore, this procedure may facilitate laboratory workflow, as well as the
      organization of multicenter studies, which requires analyses to be conducted in a
      central core laboratory.

PMID- 22974656
TI  - Intravenous vasopressin for the prevention of nontarget gastrointestinal
      embolization during liver-directed cancer treatment: experimental study in a
      porcine model.
AB  - PURPOSE: The aim of this study was to evaluate the potential for intravenous
      vasopressin to reduce the risk of nontarget gastrointestinal embolization during
      transcatheter liver-directed cancer therapies in a porcine model. MATERIALS AND
      METHODS: An angiographic catheter was used to select the celiac or common hepatic
      artery under fluoroscopic guidance in six anesthetized pigs. After angiography of
      the hepatic and splanchnic territories was performed, technetium-99m
      macroaggregated albumin ((99m)Tc-MAA) was injected through the catheter. Serial
      arteriograms were obtained before, every 5 minutes during, and after peripheral
      intravenous vasopressin infusion at 0.4 U/min for a minimum of 20 minutes. After
      10 minutes of infusion, indium-111 ((111)In)-MAA was injected through the
      arterial catheter. Quantitative comparisons of liver and gastrointestinal
      activity using dual-isotope single-photon emission computed tomography (SPECT)/CT
      imaging were performed. RESULTS: Catheter angiography demonstrated reduced blood
      flow to the splanchnic vasculature while maintaining blood flow through the
      hepatic arteries during vasopressin infusion. Angiographic findings correlated
      with the relative distribution of (99m)Tc-MAA (before the vasopressin infusion)
      and (111)In-MAA (after the vasopressin infusion) on SPECT/CT. The increased ratio
      of liver to gastrointestinal tract activity during the vasopressin infusion was
      statistically significant (6.2:11.4, respectively; P = .018). CONCLUSIONS:
      Intravenous vasopressin reduces arterial blood flow to the splanchnic vasculature
      while preserving hepatic arterial blood flow in a healthy porcine model.
      Intraprocedural vasopressin administration has the potential to benefit liver
      directed cancer therapies by enhancing tumor targeting as well as preventing the
      unintended delivery of bland embolic, chemoembolic, or radioembolic agents into
      the gastrointestinal vascular territories.

PMID- 22974657
TI  - The midfoot load shows impaired function after ankle arthrodesis.
AB  - BACKGROUND: A large number of parameters are registered by pedobarography,
      usually requiring a research setting for interpretation. The purpose of this
      study was to evaluate which pedobarographic parameters (adjusted for walking
      speed and body weight) discriminate between healthy volunteers and patients after
      ankle or tibiotalocalcaneal arthrodesis. Furthermore, we evaluated which
      parameters are associated with the American Orthopaedic Foot and Ankle Society
      (AOFAS) score. METHODS: Thirty-five healthy volunteers, 57 patients with ankle
      and 42 with tibiotalocalcaneal arthrodesis were assessed by AOFAS scores and
      dynamic pedobarography. The arthrodesis patients were further investigated with
      radiographs. Median follow up was 4 years. Eighteen basic parameters were
      measured each in the hind-, mid-, and forefoot. For dimension reduction, we
      represented a pre-selected set of 9 parameters by two indices (load, rollover).
      We used ordinal logistic and multiple linear regression to address the questions.
      FINDINGS: The midfoot index of load was the most important pedobarographic
      predictor (interquartile range odds ratio 100; 95% confidence interval 13, 771)
      for belonging to the healthy volunteers rather than the ankle or
      tibiotalocalcaneal arthrodesis groups. Similarly, it was an independent predictor
      for the AOFAS score (interquartile range effect 5 points; 95% confidence interval
      1, 9). Healthy volunteers had a deeper midfoot depression in the force/pressure
      time graphs compared to patients after arthrodesis. INTERPRETATION: When
      evaluating foot function after ankle or tibiotalocalcaneal arthrodesis, the
      interpretation of a large number of pedobarographic parameters can be reduced to
      the interpretation of the midfoot index of load and the evaluation of the
      force/pressure time graphs.

PMID- 22974658
TI  - Distinct ligand-dependent and independent modes of thyroid hormone receptor
      (TR)/PGC-1alpha interaction.
AB  - Thyroid hormone receptor (TR)/peroxisome proliferator activated receptor
      coactivator (PGC-1alpha) interactions are required for T(3)-dependent
      transcriptional responses involved in adaptive thermogenesis and liver. Thus, it
      is important to define TR/PGC-1alpha contact modes and to understand their
      significance in gene expression. Previous studies have shown that TRbeta1
      recruits PGC-1alpha to target promoters via contacts between the hormone
      dependent TRbeta1 activation function 2 (AF-2) in the C-terminal ligand binding
      domain (LBD) and a major PGC-1alpha nuclear receptor (NR) interaction box
      (consensus LxxLL) at amino acids 142-146. While our studies verify the existence
      and importance of this interaction, we present evidence that TRbeta1 also binds
      PGC-1alpha in a second ligand and LxxLL motif independent mode and show that this
      interaction requires the TRbeta1 N-terminal domain (NTD) and the PGC-1alpha N
      terminal activation domain (AD) at amino acids 1-130. Transfection assays suggest
      that optimal PGC-1alpha coactivation requires the TRbeta1 NTD and that these
      contacts are needed for utilization of the PGC-1alpha C-terminal AD, which does
      not bind TR and is implicated in basal transcription machinery contacts. We
      propose that TR AF-1/PGC-1alpha contacts are needed for transition between
      activities of PGC-1alpha N-and C-terminal ADs in gene expression. Our findings
      provide insights into possible roles for TR and NR AF-1 in gene expression.

PMID- 22974659
TI  - G/A polymorphism in intronic sequence affects the processing of MAO-B gene in
      patients with Parkinson disease.
AB  - Monoamine oxidase B (MAO-B) plays an important role in the metabolism of
      neuroactive and vasoactive amines in the central nervous system and peripheral
      tissues. Increased levels of MAO-B mRNA and enzymatic activity have been reported
      in platelets from patients with Parkinson's and Alzheimer's diseases, however the
      triggers of enhanced mRNA levels are unknown. Our results demonstrate for the
      first time that G/A dimorphism in intron 13 sequence creates splicing enhancer
      thus stimulating intron 13 removal efficiency. The increased MAO-B protein levels
      might serve as a surrogate marker for - Parkinson disease.

PMID- 22974660
TI  - Mediational effect of meaning in life on the relationship between optimism and
      well-being in community elderly.
AB  - The purpose of the present study was to examine the mediational role of meaning
      in life on the relationship between optimism and subjective well-being in older
      adults. Two hundred and fifty community-dwelling subjects completed several
      instruments assessing the above constructs. Results from structural equation
      modeling indicated that optimism was positively associated with both meaning in
      life and subjective well-being. Furthermore, the relationship between optimism
      and wellbeing was partially mediated by meaning in life. Although numerous
      studies have found that optimism is a significant predictor of well-being, the
      current results indicate that it might not be a key predictor in elders. Our
      findings suggest that a focus on meaning in life may be a productive avenue to
      enhance subjective well-being in later life although stable internal resources
      such as optimism and pessimism impact their subjective well-being.

PMID- 22974661
TI  - Prevalence and incidence of pressure ulcers in Japanese long-term-care hospitals.
AB  - In Japan, long-term-care hospitals and facilities face the problem of quality of
      care, and providing adequate pressure ulcer care is one of the most urgent
      quality issues. Purpose of the present study was to explore the prevalence and
      incidence of pressure ulcers in long-term-care hospitals in Japan, and to
      identify factors associated with them. An anonymous questionnaire was sent to 720
      randomly sampled, long-term-care hospitals all over Japan. The prevalence and
      incidence of pressure ulcers and their factors, including organizational
      strategies for pressure ulcer prevention and management, were examined. The mean
      prevalence and incidence of pressure ulcers was 9.6 and 1.9% per month,
      respectively. Almost all hospitals had established an interdisciplinary team for
      pressure ulcer prevention, developed a clinical protocol for pressure ulcers, and
      implemented education for staff. However, 35% of the interdisciplinary teams were
      not useful, more than half of the clinical protocols were not used frequently,
      and about half of the wards did not have sufficient pressure-relieving
      mattresses. In multiple regression analyses, a low prevalence of pressure ulcers
      was associated with a lower ratio of clients with a high medical severity level
      (p=0.034), the use of a clinical protocol including the management of preventive
      devices (p=0.023), the standardized pressure ulcer assessment tool (DESIGN-R;
      p=0.017), and staff education (p=0.003). This study demonstrated a higher
      prevalence and incidence of pressure ulcers in long-term-care hospitals in Japan
      as compared to regular acute-care hospitals, as well as poor organizational
      strategies for managing pressure ulcers.

PMID- 22974662
TI  - Change in depressive status and mortality in elderly persons: results of a
      national longitudinal study.
AB  - The authors aimed to investigate whether a change in depressive status was
      associated with a change in the risk of mortality in the elderly during a four
      year follow-up period. Data came from the Survey of Health and Living Status of
      the Elderly in Taiwan. A cohort of 1784 men and women in Taiwan aged 65 or older
      who were assessed on two occasions in 1999 and 2003, and subsequently followed up
      until 2007. Depressive symptoms were assessed by the 10-item Center for
      Epidemiologic Studies Depression Scale (CES-D). The mortality risk of different
      depressive statuses was computed after adjustment for a variety of covariates.
      The data were further analyzed by gender and cause of death. Overall, chronic
      depression was associated with all-cause mortality (hazard ratio [HR], 1.66; 95%
      confidence interval [CI], 1.18-2.32) after 4 years of follow-up and controlling
      for covariates. When analyzing by gender, incident depression was associated with
      mortality in males only (HR=1.54; 95% CI=1.04-2.27). In females, only chronic
      depression was associated with a higher risk of mortality (HR=1.77; 95% CI=1.08
      2.88). The increased risk of mortality with incident depression in males and
      chronic depression in females was attributed to non-cardiovascular disease (non
      CVD) causes more than to CVD causes. In males, chronic depression predicted a
      higher incidence of CVD deaths. While chronic depression confers a greater risk
      of mortality in older women, incident depression predicts increased mortality in
      older men. The link between changing depressive status, gender, ethnicity and
      mortality warrants further investigation.

PMID- 22974663
TI  - RNA interference targeting RelB attenuates liver ischemia/reperfusion injury.
AB  - BACKGROUND: RNA interference targeting RelB can significantly attenuate
      ischemia/reperfusion (I/R)-induced renal dysfunction, but its roles in liver I/R
      injury remain to be defined. We have investigated whether siRNA targeting of RelB
      in liver could also elicit protection against I/R injury. MATERIALS AND METHODS:
      A RelB miRNA RNAi expression plasmid, a scrambled plasmid, or phosphate-buffered
      saline (50 MUg of the plasmid diluted in phosphate-buffered saline, 8% wt/vol)
      were rapidly injected, within 6-8 s, into mouse tail veins 24 h before liver I/R.
      Mice were subjected to 30 min of 70% hepatic ischemia or to a sham operation. Six
      h after reperfusion, blood and liver tissue samples were collected for subsequent
      assays. RESULTS: The expression level of RelB was reduced in the RelB RNAi group
      compared with the control group, while it was increased in the I/R group. In the
      sham group, malondialdehyde, myeloperoxidase (MPO), and superoxide dismutase
      serum levels were almost the same, but the alanine aminotransferase level in the
      untreated group was 20- to 25-fold lower than in the other groups. In I/R-treated
      mice, although alanine aminotransferase, malondialdehyde, and MPO serum levels in
      the RelB RNAi group were lower than in other groups, all were higher than in the
      sham group. Silencing RelB could inhibit the decrease of superoxide dismutase
      activity and the upregulation of MPO and tumor necrosis factor alpha induced by
      I/R injury. CONCLUSIONS: Silencing RelB can protect the liver against I/R-induced
      damage. Therefore, it is a promising therapeutic target for protection against
      I/R injury in the liver.

PMID- 22974664
TI  - Elderly and long-term care trends and policy in Taiwan: challenges and
      opportunities for health care professionals.
AB  - The purpose of this article is to address the trends and policy of elderly and
      long-term care in Taiwan. In response to the increasing demand of an aging
      society, healthcare professionals play crucial roles in elderly and long-term
      care and quality assurance of services. This article focuses on the current
      situation of elderly health care, demands of long-term care, long-term care
      policy in Taiwan, draft of the Long-term Care Services Act, and draft of the Long
      term Care Insurance Act. After the 10-year long-term care project was proposed by
      the Taiwan government, the supply of health care services and demand for long
      term care have created many challenges and opportunities for innovative health
      professional development. Challenges consist of low old dependency ratio caused
      by low birth rate, lack of elderly and long-term care related manpower, services
      and education reform related to long-term care for the future society, and
      interprofessional collaboration and team work of long-term care. Opportunities
      include expanding the roles and the career pathways of healthcare professionals,
      promoting the concepts of active aging and good quality of life, and developing
      industrial cooperation related to long-term care services. Under these
      circumstances, healthcare professonals are actively involved in practice,
      education and research of long-term care services that ensure elderly and
      disabled people can live a healthier and better life.

PMID- 22974665
TI  - Waist circumference, body mass index, serum uric acid, blood sugar, and
      triglyceride levels are important risk factors for abnormal liver function tests
      in the Taiwanese population.
AB  - Several studies have found that metabolic syndrome and uric acid level are
      related to abnormal liver function test results. The aim of this study was to
      explore the associations of risk factors [including blood pressure, blood sugar,
      total cholesterol, triglyceride, uric acid, waist circumference and body mass
      index (BMI) measurements] with abnormal liver function in the Taiwanese
      population.In total, 11,411 Taiwanese adults were enrolled in this study. Blood
      pressure was assessed according to the Seventh Report of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure criteria, fasting blood sugar level according to the Bureau of Health
      Promotion, Department of Health, R.O.C., criteria, total cholesterol and
      triglyceride levels according to the Third Report of the National Cholesterol
      Education Program Adult Treatment Panel III criteria, BMI according to the Asia
      Pacific criteria, and waist circumference according to the Revised Diagnostic
      Criteria of Metabolic Syndrome in Taiwan. The prevalence of a past history of
      hypertension and diabetes mellitus was 17.7% and 6.5%, respectively, and the
      rates of abnormal measurements of blood pressure, BMI, waist circumference,
      fasting blood sugar, triglyceride, total cholesterol, uric acid (male/female),
      aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were 76.2%,
      67.6%, 40.0%, 28.6%, 30.6%, 57.3%, 37.9%/21.9%, 14.6% and 21.3%, respectively.
      Multivariate analysis showed that waist circumference, BMI, serum uric acid,
      blood sugar, and triglyceride levels were related to abnormal AST and ALT
      (p<0.05), but the odds ratio for waist circumference was larger than that for
      BMI. In conclusion, waist circumference, BMI, serum uric acid, blood sugar, and
      triglyceride levels are important risk factors for abnormal AST and ALT readings
      in Taiwanese adults. Waist circumference might be a better indicator of risk of
      abnormal liver function than BMI.

PMID- 22974666
TI  - Prescriptions for angiotensin-converting enzyme inhibitors/angiotensin receptor
      blockers and monitoring of serum creatinine and potassium in patients with
      chronic kidney disease.
AB  - Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers
      (ACEIs/ARBs) are commonly used in patients with chronic kidney disease (CKD). We
      studied the status of ACEI/ARB prescriptions and serum creatinine (Scr) and
      potassium monitoring in CKD patients. A retrospective observational study was
      conducted on patients who had at least two sets of Scr data at outpatient visit.
      Estimated glomerular filtration rate (eGFR) based on the second Scr value was
      calculated using the Modification of Diet in Renal Disease four-variable
      equation. CKD was defined and staged according to the National Kidney Foundation
      Disease Outcomes Quality Initiative Guideline. Patients with diabetes and/or
      hypertension with an eGFR over 60 mL/min/1.73 m(2) and without proteinuria were
      defined as the CKD-at-risk group. The percentages and factors associated with
      ACEI/ARB prescription and Scr and potassium monitoring were calculated and
      analyzed by logistic regression. Among the 5714 subjects included, ACEIs/ARBs
      were prescribed to over 50% of patients in the CKD-at-risk group and in CKD
      stages 1-5. After adjusting for age, sex, potassium level, eGFR, and co
      morbidities, the odds ratios for prescriptions of ACEIs/ARBs were 1.66 [95%
      confidence interval (CI) 1.44-1.91, p < 0.001) and 2.80 (95% CI 2.12-3.70, p <
      0.001) in CKD stage 3, and stages 4 and 5, respectively, compared with the
      reference group (eGFR>=60 mL/min/1.73 m(2)). During the year of ACEI/ARB
      treatment, Scr was monitored in 91.6% of ACEI/ARB-treated patients, while
      potassium was monitored in only 38.1%. Renal function status was the independent
      factor for monitoring of Scr and potassium. In conclusion, prescription of
      ACEIs/ARBs was common in all stages of CKD. Most patients underwent Scr
      monitoring, but potassium monitoring was less frequent, and this should be
      improved in clinical practice.

PMID- 22974667
TI  - Kinematic analysis of leg alignment during conventional versus navigated total
      knee arthroplasty: initial results of a prospective study.
AB  - Current kinematic navigation systems provide real-time spatial analyses of leg
      alignments during total knee arthroplasty (TKA) instead of delayed radiographic
      verification after surgery. A prospective study was conducted to investigate leg
      alignments of TKAs that underwent different surgical guidance [intramedullary
      (IM) jig-based vs. navigation-assisted] using a kinematic navigation system.
      Since May 2007, patients admitted for primary TKA were considered for inclusion.
      Within 6 months, 38 sets of intraoperative analyses on the operated legs have
      been performed. Excluding seven unreliable data sets, 15 conventional IM jig
      based TKAs and 16 navigation-assisted TKAs were available. The leg alignments in
      maximum knee extension were retrieved for comparison. Although similar final
      coronal alignments were accurately achieved in both groups (0.21 valgus in the IM
      group vs. 0.17 valgus in the NA group, p=0.993), a more flexed sagittal axis was
      constructed with conventional IM jigs (1.93 flexion in the IM group vs. 0.58
      extension in the NA group, p<0.05). The study suggests that comparable coronal
      precision could be achieved with conventional IM jigs by trained surgeons,
      although computer-assisted navigation is a documented method to restore accurate
      alignment. Different sagittal alignments observed in this study indicate the
      inherent discrepancy between different surgical guides as well as their according
      concepts.

PMID- 22974668
TI  - Evaluating the accuracy of tooth color measurement by combining the Munsell color
      system and dental colorimeter.
AB  - As we pay increasing attention to dental aesthetics, tooth color matching has
      become an important part of daily dental practice. This aim of this study was to
      develop a method to enhance the accuracy of a tooth color matching machine. The
      Munsell color tabs in the range of natural human teeth were measured using a
      tooth color measuring machine (ShadeEye NCC). The machine's accuracy was analyzed
      using an analysis of variance test and a Tukey post-hoc test. When matching the
      Munsell color tabs with the ShadeEye NCC colorimeter, settings of Chroma greater
      than 6 and Value less than 4 showed unacceptable clinical results. When the
      CIELAB mode was used, the a* value (which represents the red-green axis in the
      Commission Internationale de l'Eclairage color space) made no significant
      difference (p=0.84), the L* value (which represents the lightness) resulted in a
      negative correlation, and the b* value (which represents the yellow-blue axis)
      resulted in a positive correlation with DeltaE. When the Munsell color tabs and
      the Vitapan were measured in the same mode and compared, the inaccuracies showed
      that the Vitapan was not a proper tool for evaluating the stability and accuracy
      of ShadeEye NCC. By knowing the limitations of the machine, we evaluated the data
      using the Munsell color tabs; shade beyond the acceptable range should be
      reevaluated using a visual shade matching method, or if measured by another
      machine, this shade range should be covered to obtain more accurate results.

PMID- 22974669
TI  - Safety and resource utilization of anterior cervical discectomy and fusion.
AB  - Degenerative cervical spondylosis (DCS) is part of the aging process and is the
      most common reason for degenerative changes with the spinal column. Anterior
      cervical discectomy and fusion (ACDF) is a major option for operative management
      of DCS in our institution. This retrospective study investigated the frequency of
      postoperative complications and resource utilization in 145 patients who
      underwent ACDF procedures from January 2009 to December 2011. Patients with
      degenerative changes that involved cervical intervertebral levels C1-C2, spinal
      injury of traumatic origin, spinal tumors, or previous cervical fusion were
      excluded. Patients were then further classified into two groups: (1) level 1 or 2
      disease (Group M) and (2) level 3 or 4 disease (Group S). Measures of mortality,
      complications after surgery as well as immediate reoperation for any reason were
      evaluated. Operation time, length of hospital stay, and hospitalization cost were
      defined as resource utilization. Ninety seven patients met the inclusion criteria
      and were further reviewed to characterize the sample better. There were no
      hematomas, airway complications or deaths, except in one patient who developed
      postoperative hemorrhage that required immediate surgical intervention, and
      resolved without any neurological deficit or casualty. Resource utilization
      indicated that the average operation time for Group S was significantly higher
      than for Group M (4.31+/-1.25 vs. 2.88+/-0.90 hours, p<0.0001). There were no
      significant differences in length of hospital stay and hospitalization cost
      between the two groups (p=0.265 and p=0.649). Our results indicate that
      neurosurgical intervention is safe for patients with DSC. Postoperative
      complication rates associated with these procedures are low. When surgery is
      considered appropriate for patients with multilevel diseases, these data suggest
      that ACDF is a safe surgical option.

PMID- 22974670
TI  - Factor structure, reliability, and validity of the Chinese version of the School
      Bullying Experience Questionnaire.
AB  - The aims of this study were to examine the factor structure, internal
      consistency, 1-month test-retest reliability, and congruent validity of the
      Chinese version of the School Bullying Experience Questionnaire (C-SBEQ). Study
      1, in which 5751 Taiwanese adolescents in Southern Taiwan participated, examined
      the adequacy of the original four-factor structure of the C-SBEQ using
      confirmatory factor analysis (CFA) and internal-consistency reliability using
      Cronbach alpha. Study 2, in which 108 adolescents in Southern Taiwan
      participated, examined the 1-month test-retest reliability using intraclass
      correlation coefficients (ICCs). We examined the congruent validity of the C-SBEQ
      by examining the consistency between self-reported and teacher- and classmate
      nominated experiences of bullying involvement in Study 2. The results of CFA
      supported the four-factor structure of the C-SBEQ in Taiwanese adolescents. The
      test-retest and internal reliability values of all subscales of the C-SBEQ were
      at acceptable to satisfactory levels. Nominated adolescents had significantly
      higher self-reported scores on three C-SBEQ subscales than non-nominated ones,
      and the levels of agreement between self-reported and nominated victims were
      moderate. The results of this study indicate that the C-SBEQ is appropriate for
      assessing bullying experiences in Taiwanese adolescents.

PMID- 22974671
TI  - Parachute mitral valve accompanied by bicuspid aortic valve on three-dimensional
      transesophageal echocardiography.
AB  - We report the findings of three-dimensional (3D) transesophageal echocardiography
      (TEE) in a patient with a parachute mitral valve (MV) accompanied by aortic valve
      (AV) malformation. The results indicated an enhanced echo in MV anterior leaves,
      incrassate, and shortened subvalvular chordae tendineae, and posteromedial
      papillary muscle that had echo reinforcement, calcification, retroposition, and a
      significant decrease compared with anterolateral papillary muscle. In addition,
      the anterolateral papillary muscle was huge, with the bilateral papillary muscles
      fused partly, and the posterior subvalvular chordae tendineae incrassate,
      shortened, and attached parachute-like to the anterolateral papillary muscle. The
      MV appeared dome-shaped for the open limit in diastole with an MV area of 1.6 cm.
      Moreover, the left ventricle increased in size and the bicuspid AV was malformed.
      Continuous wave Doppler angiograph showed that the flow rate increased to 398
      cm/seconds at the AV orifice area. A 3D form of the MV structure was observed
      from the left ventricle using 3D-TEE inspection. The anterolateral papillary
      muscle was fused with its posteromedial homologue. The chordae tendineae was
      attached to the anterolateral papillary with the parachute-like structure,
      indicating dome movement.

PMID- 22974672
TI  - Lymphoepithelioma-like carcinoma of ureter-a rare case report and review of the
      literature.
AB  - Lymphoepithelioma-like carcinoma (LELC) is best known to occur in the
      nasopharynx. When LELC occurs in the urinary tract, this extremely rare neoplasm
      most commonly affects the bladder but has also been reported in the renal pelvis,
      ureter, prostate [1], and urethra [2]. We present a case of LELC arising in the
      right proximal ureter of a 64-year-old male patient with hydronephrosis and
      nausea. Computed tomography demonstrated right ureter tumor. On biopsy, the
      patient was diagnosed with infiltrating urothelial carcinoma. An operation
      consisting of right nephroureterectomy and bladder cuff removal was carried out.
      The pathologic examination showed pure subtype of LELC, pT3N0. Unlike
      lymphoepithelioma in the nasopharynx, immunohistochemical analysis of this
      urinary LELC was negative for the Epstein-Barr virus. No disease progression was
      noted at 6 months' follow-up. Only eight previous cases of LELC involving the
      ureter have been reported, and a review of the available literature and a summary
      of ureter cases are presented here. This is the first report of a ureteral LELC
      case and third urothelial LELC cases [3] in Taiwan.

PMID- 22974673
TI  - Pectoralis major pyomyositis in an 88-year-old man: Is tooth extraction
      bacteremia the source?

PMID- 22974674
TI  - Topography of sleep slow wave activity in children with attention
      deficit/hyperactivity disorder.
AB  - INTRODUCTION: Sleep slow wave activity (SWA, EEG power between 1 and 4.5 Hz) is a
      major characteristic of non-rapid eye movement (NREM) sleep, which seems to be
      critically involved in cortical plasticity. Studies using high-density
      electroencephalography (hd-EEG) showed that the topographical distribution of SWA
      mirrors cortical maturation, expressing a local maximum that is characteristic
      for a certain age range. We compared the sleep EEG of children with attention
      deficit/hyperactivity disorder (ADHD) with healthy controls to explore
      differences in sleep SWA. METHODS: All-night hd-EEG recordings (128 electrodes)
      were performed in a group of nine children diagnosed with ADHD and nine age- and
      sex-matched healthy controls. SWA topography was calculated and contrasted
      between the groups. RESULTS: We found a local increase of SWA in a cluster of six
      electrodes over central regions in children with ADHD compared to control
      children (+17% +/- 6% SE, p < .01). This group difference was specific for the
      SWA range and stable across the night. CONCLUSIONS: Children with ADHD showed a
      less mature topographical SWA distribution in comparison to healthy children of
      the same age and sex. This neuromaturational delay in ADHD is in accordance with
      neuroimaging and behavioral studies. Thus, our study supports the use of sleep
      SWA topography as a reliable imaging tool for the study of cortical plasticity.

PMID- 22974675
TI  - The eyes are not the window to basic emotions.
AB  - Facial expressions are one of the most important ways to communicate our
      emotional state. In popular culture and in the scientific literature on face
      processing, the eye area is often conceived as a very important - if not the most
      important - cue for the recognition of facial expressions. In support of this, an
      underutilization of the eye area is often observed in clinical populations with a
      deficit in the recognition of facial expressions of emotions. Here, we used the
      Bubbles technique to verify which facial cue is the most important when it comes
      to discriminating between eight static and dynamic facial expressions (i.e., six
      basic emotions, pain and a neutral expression). We found that the mouth area is
      the most important cue for both static and dynamic facial expressions. We
      conducted an ideal observer analysis on the static expressions and determined
      that the mouth area is the most informative. However, we found an
      underutilization of the eye area by human participants in comparison to the ideal
      observer. We then demonstrated that the mouth area contains the most
      discriminative motions across expressions. We propose that the greater
      utilization of the mouth area by the human participants might come from remnants
      of the strategy the brain has developed with dynamic stimuli, and/or from a
      strategy whereby the most informative area is prioritized due to the limited
      capacity of the visuo-cognitive system.

PMID- 22974676
TI  - Interpreting success and failure in food fortification.

PMID- 22974677
TI  - Governments and academic institutions play vital roles in food fortification:
      iron as an example.

PMID- 22974679
TI  - What non-alcohol drugs are used by drinking drivers in Sweden? Toxicological
      results from ten years of forensic blood samples.
AB  - INTRODUCTION AND METHOD: Using a forensic toxicology database (TOXBASE), the
      toxicological results from 10 years of forensic blood samples from people
      arrested for driving under the influence of alcohol and/or other drugs were
      reviewed. RESULTS: Alcohol was the only drug identified in blood in N=35,704
      cases at a median blood-alcohol concentration (BAC) of 1.63 mg/g. The mean age
      (+/-SD) of these offenders was 40+/-15years and 89% were male. The median BAC was
      lower (1.30 mg/g) in drivers who had consumed alcohol and used a prescription
      drug before driving (N=1,251). The mean age of this group of traffic offenders
      was 38+/-13years and 85% were male. Both the median BAC (0.97 mg/g) and the mean
      age were lowest (36+/-11years, 92% male) in N=3,153 drivers who had consumed
      alcohol and used illicit drugs before driving. Cannabis, amphetamine, cocaine and
      morphine (metabolite of heroin) were the commonest illicit drugs identified in
      blood samples. Sedative-hypnotics (benzodiazepines) were the major prescription
      drugs co-ingested with alcohol. Poly-drug use was a common finding in these
      traffic delinquents, although individuals who only drank alcohol had a higher
      median BAC and were also several years older than drinking drivers combining
      alcohol with other drugs before driving. IMPACT ON INDUSTRY: Zero-tolerance
      legislation did not deter hard-core offenders. In future there should be more
      focus on treatment for alcohol and substance abuse disorder rather than
      conventional punishments for this type of traffic crime.

PMID- 22974678
TI  - Serum homocysteine and folate concentrations among a US cohort of adolescents
      before and after folic acid fortification.
AB  - OBJECTIVE: We assessed serum homocysteine (tHcy) and folate concentrations among
      US adolescents before and after fortification of cereal-grain products with folic
      acid, and associations with demographic, behavioural and physiological factors.
      DESIGN: Observational study conducted among participants of a randomized trial.
      SETTING: The Child and Adolescent Trial for Cardiovascular Health (CATCH) study.
      SUBJECTS: Adolescents (n 2445) in grades 8 (pre-fortification, mean age 14 years)
      and 12 (post-fortification, mean age 18 years). RESULTS: Average serum
      concentrations of tHcy, folate and vitamin B6 increased by 17 %, 16 % and 14 %,
      respectively, while serum concentrations of vitamin B12 decreased by 11 % post
      fortification. Folic acid fortification provided, on average, an additional
      intake of 118 MUg folate/d. Male sex (P < 0.0001) and white race (P = 0.0008)
      were associated with significantly greater increases in tHcy concentration, while
      increases in BMI (P = 0.006) and serum folate concentration (P < 0.0001) were
      associated with significant decreases in tHcy concentration. Female sex (P <
      0.0001), non-smoking (P < 0.0001), use of multivitamins (P < 0.0001) and higher
      dietary intake of folate (P = 0.001) were associated with significantly greater
      increases in serum folate concentrations. From grade 8 to grade 12, the upward
      age trend in serum tHcy concentration was uninterrupted in its course (P > 0.50);
      whereas serum folic acid concentration showed a downward trend that incurred a
      discrete jump upward (17 % higher; P < 0.0001) with fortification. These trends
      differed significantly for males v. females (P < 0.001 for interaction).
      CONCLUSIONS: Fortification had a significant impact on improving folate status
      but not serum tHcy concentrations among US adolescents.

PMID- 22974680
TI  - Heavy trucks, conspicuity treatment, and the decline of collision risk in
      darkness.
AB  - INTRODUCTION: The influence of amendments to Federal Motor Vehicle Safety
      Standard (FMVSS) 108, requiring conspicuity treatments on heavy tractors and
      trailers, was determined in analyses of the odds of fatal collisions in darkness.
      METHOD: Comparisons were made between crashes in which conspicuity treatment was
      likely relevant, and those in which it was likely irrelevant. RESULTS: Over
      23years, the odds that a fatal collision involving a heavy truck occurred in
      darkness declined by 58% among relevant crashes, while little decline was
      observed for irrelevant crashes. Disaggregation into crash types revealed the
      largest declines occurred in fatal rear-end and angle collisions. A parallel
      analysis of light vehicles also found declines but no differences among crash
      type. Similar trends were also observed for nonfatal rear end collisions.
      CONCLUSION: The results suggest that detection failure may have contributed to
      the risk of striking a tractor-semitrailer in darkness, and that conspicuity
      treatments have reduced this risk. IMPACT ON INDUSTRY: Conspicuity treatments
      appear to reduce risk of collision into heavy trucks in darkness. It is likely
      that this benefit would also extend to other vehicles that are not included in
      the FMVSS 108 regulation (e.g., buses, single unit trucks, recreational
      vehicles), although many are so equipped, regardless of the regulation.

PMID- 22974681
TI  - Passengers of impaired drivers.
AB  - INTRODUCTION: The aims of this study are: (a) to estimate the prevalence of
      passengers riding with alcohol-impaired drivers; (b) to investigate the role of
      demographic factors (age, gender, race/ethnicity, educational status) and
      relevant driving conditions (time of the day, trip origin, vehicle ownership) on
      shaping the likelihood of alcohol-impaired driving; (c) to identify and estimate
      the prevalence of passengers as alternative drivers (PADs); and (d) to examine
      the role that vehicle ownership plays in shaping the occurrence of PADs. METHOD:
      Data came from a unique convenience sample of passengers obtained from the 2007
      National Roadside Survey, a random sample of drivers from the 48 contiguous
      states. RESULTS: The prevalence of PADs in the targeted population (mostly
      weekend night vehicles) was higher with drivers at .00<BAC<.08 (17%-43%) than at
      BAC>=.08 (6%-29%) drivers. The evidence suggests that targeted policies to
      encourage PADs to drive might be possible. However, vehicle ownership is a large
      impediment for PADs to act as designated drivers. We speculate that vehicle
      ownership may be a main reason for the less-than expected success of the
      "designated driver" concept.

PMID- 22974682
TI  - Risk factors associated with bus accident severity in the United States: a
      generalized ordered logit model.
AB  - INTRODUCTION: Recent years have witnessed a growing interest in improving bus
      safety operations worldwide. While in the United States buses are considered
      relatively safe, the number of bus accidents is far from being negligible,
      triggering the introduction of the Motor-coach Enhanced Safety Act of 2011.
      METHOD: The current study investigates the underlying risk factors of bus
      accident severity in the United States by estimating a generalized ordered logit
      model. Data for the analysis are retrieved from the General Estimates System
      (GES) database for the years 2005-2009. RESULTS: Results show that accident
      severity increases: (i) for young bus drivers under the age of 25; (ii) for
      drivers beyond the age of 55, and most prominently for drivers over 65 years old;
      (iii) for female drivers; (iv) for very high (over 65 mph) and very low (under 20
      mph) speed limits; (v) at intersections; (vi) because of inattentive and risky
      driving.

PMID- 22974683
TI  - Occupational injuries among U.S. correctional officers, 1999-2008.
AB  - OBJECTIVE: This study describes fatal and nonfatal occupational injuries among
      U.S. correctional officers. METHODS: Fatal injuries were obtained from the Census
      of Fatal Occupational Injuries; nonfatal injuries were identified from the
      National Electronic Injury Surveillance System- Occupational Supplement. RESULTS:
      From 1999-2008, there were 113 fatalities and an estimated 125,200 (CI=+/-70,100)
      nonfatal injuries were treated in emergency departments. Assaults and violent
      acts (n=45, 40%) and transportation related fatalities (n=45, 40%) were the two
      primary fatal injury events. Assaults and violent acts (n=47,500 (CI=+/-24,500),
      38%) and bodily reaction and exertion (n=25,400 (CI=+/-16,800), 20%) were the
      leading events resulting in nonfatal injuries. CONCLUSIONS: While workplace
      violence is the primary cause of both fatal and nonfatal injuries among
      correctional officers, transportation events and bodily reactions are also
      leading causes of occupational injury. Future research is needed to identify risk
      factors unique to these events and develop appropriate prevention and
      intervention efforts. IMPACT ON INDUSTRY: This study adds to the literature on
      occupational injuries among correctional officers and provides a national level
      description of fatal and nonfatal injuries across a 10-year period. Given that
      assaults and violent acts, transportation events, and bodily reaction and
      exertion were significant injury events, future research should describe detailed
      injury circumstances and risk factors for correctional officers unique to these
      events. This would allow appropriate prevention and control efforts to be
      developed to reduce injuries from these events.

PMID- 22974684
TI  - A survey of light-vehicle driver education curriculum on sharing the road with
      heavy vehicles.
AB  - INTRODUCTION: Light-vehicle driver education programs that contain content about
      sharing the road with heavy vehicles may be helpful in reducing future light
      vehicle/heavy-vehicle interactions. However, the extent of curricula in the
      United States including such content is unclear. METHOD: Researchers developed an
      online survey targeted at instructors/administrators of state driver education
      programs to identify curricula addressing heavy vehicles and to determine
      perceived effectiveness. RESULTS: Ninety-one percent of respondents indicated
      that the light-vehicle driver education curriculum they teach/administer included
      a component covering how to safely share the road with heavy vehicles (82%
      perceived this component to be effective). DISCUSSION: Although a large
      proportion of these programs included a component on how to safely share the road
      with heavy vehicles, participants indicated there may be room for improvement.
      IMPACT ON INDUSTRY: Participants recommended that future improvements to driver
      education programs include updated materials and student hands-on experience with
      heavy vehicles.

PMID- 22974685
TI  - Graduated driver licensing research, 2010-present.
AB  - This is the latest in a series of reviews of research on graduated driver
      licensing (GDL) published in the Journal of Safety Research, covering the period
      January 1, 2010-June 1, 2012 and works in progress. The intent is to keep
      researchers and policy makers current regarding the existing state of knowledge
      about GDL, and to identify information gaps and areas where clarification of
      research findings are needed. The recent research indicates that we continue to
      learn about ways to extend GDL benefits, but there remain important questions in
      need of further inquiry. In terms of impact on industry, the review provides
      guidance for the future GDL research agenda.

PMID- 22974686
TI  - The Ergonomic Program Implementation Continuum (EPIC): integration of health and
      safety--a process evaluation in the healthcare sector.
AB  - INTRODUCTION: This article presents a health and safety intervention model and
      the use of process evaluation to assess a participatory ergonomic intervention.
      METHOD: The effectiveness of the Ergonomic Program Implementation Continuum
      (EPIC) was assessed at six healthcare pilot sites in Ontario, Canada. The model
      provided a framework to demonstrate evaluation findings. RESULTS: Participants
      reported that EPIC was thorough and identified improvements related to its use.
      Participants believed the program contributed to advancing an organizational
      culture of safety (COS). Main barriers to program uptake included resistance to
      change and need for adequate funding and resources. The dedication of
      organizational leaders and consultant coaches was identified as essential to the
      program's success. IMPACT ON INDUSTRY: In terms of impact on industry, findings
      contribute to the evidence-based knowledge of health and safety interventions and
      support use of the framework for creating a robust infrastructure to advance
      organizational COS and link staff safety and wellness with patient safety in
      healthcare.

PMID- 22974687
TI  - Linking empowering leadership to safety participation in nuclear power plants: a
      structural equation model.
AB  - INTRODUCTION: Safety participation is of paramount importance in guaranteeing the
      safe running of nuclear power plants. METHOD: The present study examined the
      effects of empowering leadership on safety participation. RESULTS: Based on a
      sample of 495 employees from two Spanish nuclear power plants, structural
      equation modeling showed that empowering leadership has a significant
      relationship with safety participation, which is mediated by collaborative team
      learning. In addition, the results revealed that the relationship between
      empowering leadership and collaborative learning is partially mediated by the
      promotion of dialogue and open communication. CONCLUSIONS: The implications of
      these findings for safety research and their practical applications are outlined.
      IMPACT ON INDUSTRY: An empowering leadership style enhances workers' safety
      performance, particularly safety participation behaviors. Safety participation is
      recommended to detect possible rule inconsistencies or misunderstood procedures
      and make workers aware of critical safety information and issues.

PMID- 22974688
TI  - Adult opinions about the age at which children can be left home alone, bathe
      alone, or bike alone: Second Injury Control and Risk Survey (ICARIS-2).
AB  - PROBLEM: This study describes adult opinions about child supervision during
      various activities. METHODS: Data come from a survey of U.S. adults. Respondents
      were asked the minimum age a child could safely: stay home alone; bathe alone; or
      ride a bike alone. Respondents with children were asked if their child had ever
      been allowed to: play outside alone; play in a room at home for more than 10
      minutes alone; bathe with another child; or bathe alone. RESULTS: The mean age
      that adults believed a child could be home alone was 13.0 years (95% CI=12.9
      13.1), bathe alone was 7.5 years (95% CI=7.4-7.6), or bike alone was 10.1 years
      (95% CI=10.0-10.3). There were significant differences by income, education, and
      race. DISCUSSION: Assessing adult's understanding of the appropriate age for
      independent action helps set a context for providing guidance on parental
      supervision. Guidelines for parents should acknowledge social norms and child
      development stages. IMPACT ON INDUSTRY: Knowledge of social norms can help guide
      injury prevention messages for parents.

PMID- 22974689
TI  - Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles
      in ovarian cancer cell spheroid model.
AB  - We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using
      an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an
      advanced clinical stage and develop resistance to standard of care
      platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had
      limited benefits in refractory patients. In this study, we used drug-resistant
      spheroid cultures of ovarian carcinoma to evaluate the uptake and cytotoxicity of
      an antibody-targeted doxorubicin formulation. Doxorubicin was encapsulated in
      polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) conjugated micelles. The
      doxorubicin-loaded PEG-PE micelles (MDOX) were further decorated with a cancer
      cell-specific monoclonal 2C5 antibody to obtain doxorubicin-loaded immunomicelles
      (2C5-MDOX). Targeting and resulting toxicity of doxorubicin-loaded PEG-PE
      micelles were evaluated in three dimensional cancer cell spheroids. Superior
      accumulation of 2C5-MDOX compared to free doxorubicin or untargeted MDOX in
      spheroids was evidenced both by flow cytometry, fluorescence and confocal
      microscopy. Interestingly, even higher toxicity was measured by lactate
      dehydrogenase release and terminal deoxynucleotidyl transferase dUTP nick end
      labeling of targeted doxorubicin micelles in Bcl-2 overexpressing adriamycin
      resistant spheroids. Overall, these results support use of spheroids to evaluate
      tumor targeted drug delivery.

PMID- 22974691
TI  - The use of chromophore and fluorophore degradation to quantitate UV dose: FD&C
      dyes as chemical identicators for UV sterilization.
AB  - The accurate measurement of ultraviolet (UV) irradiation, especially within a
      container or vessel is one of the challenges facing the broad implementation of
      UV sterilization. Currently, biological indicators are the best method to
      determine whether an applied UV dose has the necessary efficacy to achieve
      sterilization. To overcome some of the challenges of using a biological
      indicator, chemical indicators based upon the degradation of food, drug and
      cosmetic (FD&C) dyes were developed. In this work, the relationship between UV
      dose and dye degradation was elucidated and used to create standard curves which
      could be used as a quantitative measurement system. The use of dye degradation as
      a measurement of UV dose is especially useful when the levels of UV irradiation
      within a container cannot be measured directly. Additionally, due to the highly
      colored nature of the FD&C dyes, the visual changes present upon dye irradiation
      can be used as a qualitative visual indicator of the UV dose.

PMID- 22974692
TI  - The surface emissions trap: a new approach in indoor air purification.
AB  - A new device for stopping or reducing potentially irritating or harmful emissions
      from surfaces indoors is described. The device is a surface emissions trap
      prototype and consists of an adsorbent sheet with a semipermeable barrier
      surrounded by two thin nonwoven layers. The trap may be applied directly at the
      source of the emissions e.g. at moisture-affected floors and walls, surfaces
      contaminated by chemical spills etc. This results in an immediate stop or
      reduction of the emitting pollutants. The trap has a very low water vapor
      resistance thus allowing drying of wet surfaces. In laboratory experiments
      typically 98% reduction of air concentrations of volatile organic compounds and a
      virtually total reduction of mold particle-associated mycotoxins was observed.
      The surface emissions trap may represent a convenient and efficient way of
      restoring indoor environments polluted by microbial and other moisture-associated
      emissions.

PMID- 22974693
TI  - Cardiac magnetic resonance and the need for routine cardiac catheterization in
      single ventricle patients prior to Fontan: a comparison of 3 groups: pre-Fontan
      CMR versus cath evaluation.
AB  - OBJECTIVES: This study investigated whether cardiac magnetic resonance (CMR) and
      echocardiography (echo) can replace catheterization (cath) for routine evaluation
      prior to Fontan and under what circumstances CMR and cath are used together.
      BACKGROUND: Routine cath prior to Fontan has been utilized for years; noninvasive
      methods, however, may be sufficient. METHODS: This study reviews clinical data in
      119 consecutive patients investigating 3 groups: those who underwent CMR alone
      (MR; n = 41), cath alone (C; n = 41), or both cath and CMR (C+M; n = 37) prior to
      Fontan. RESULTS: No clinically significant differences were noted in patient
      characteristics, hemodynamics, or clinical status prior to or after surgery
      between the C and MR groups. CMR added information in 82%. There were no
      discrepant findings between CMR and cath data in the C+M group. Diagnostic
      success was >=95% in all groups. Of those undergoing Fontan completion, the C+M
      group had similar outcomes to C and MR; C and CMR were utilized in combination to
      assess aortopulmonary collaterals or the need for an intervention or evaluate its
      success. Echo could not delineate pulmonary arterial anatomy in 46% to 53% of
      patients. The C+M and C groups were exposed to 6.8 +/- 4.1 mSv of radiation.
      CONCLUSIONS: Single ventricle patients not requiring an intervention can undergo
      successful Fontan completion with CMR and echo alone with similar short-term
      outcomes to C, which was used as a control, preventing an invasive test and
      exposure to radiation. CMR can add information in a significant number of
      patients. Cath and CMR are utilized together for interventions and assessment of
      aortopulmonary collaterals.

PMID- 22974690
TI  - Depressive symptoms in prodromal Huntington's Disease correlate with Stroop
      interference related functional connectivity in the ventromedial prefrontal
      cortex.
AB  - Huntington's Disease (HD) is a neurodegenerative disorder caused by a cytosine
      adenine-guanine (CAG) triplet repeat-expansion in the Huntingtin (HTT) gene.
      Diagnosis of HD is classically defined by the presence of motor symptoms;
      however, cognitive and depressive symptoms frequently precede motor
      manifestations, and may occur early in the prodromal phase. There are sparse data
      so far on functional brain correlates of depressive symptoms in prodromal HD. A
      Stroop color-naming test was administered to 32 subjects in the prodromal phase
      of HD and 52 expansion-negative controls while performing functional magnetic
      resonance imaging at 3Tesla. Networks of functional connectivity were identified
      using group independent component analysis, followed by an analysis of functional
      network interactions. A contrast of temporal regression-based beta-weights was
      calculated as a reflection of Stroop-interference related activity and correlated
      with Center for Epidemiologic Studies Depression (CES-D) scores. For secondary
      analysis, patients were stratified into two subgroups by median split of CAG
      repeat-length. Stroop performance was independent of HTT mutation-carrier status
      and CES-D score. Stroop-interference-related activity of the ventromedial
      prefrontal cortex-node of the default-mode network, calculated by temporal
      regression beta-weights, was more highly correlated with depressive symptoms in
      subjects in the prodromal phase of HD than in controls, differing significantly.
      The strength of this correlation and its difference from controls increased when
      a subgroup of patients with longer CAG repeat lengths was analyzed. These
      findings suggest that depressive symptoms in prodromal HD subjects may reflect
      altered functional brain network activity in the context of early HD-related
      brain alterations.

PMID- 22974694
TI  - Double aortic arch presents with dysphagia as initial symptom.

PMID- 22974695
TI  - No Editor's Page this month.

PMID- 22974696
TI  - Safety of dabigatran versus warfarin for periprocedural anticoagulation in
      patients undergoing ablation for atrial fibrillation.

PMID- 22974699
TI  - What's contrasting contrast?

PMID- 22974700
TI  - Dysglycemia and cardiovascular risk.

PMID- 22974701
TI  - A patient with a red eye and a murmur.

PMID- 22974702
TI  - The fish gill. Foreword.

PMID- 22974703
TI  - Thrombocytopenia and in-hospital mortality risk among ischemic stroke patients.
AB  - BACKGROUND: Thrombocytopenia has been associated with increased mortality in
      nonstroke conditions. Because its role in acute ischemic stroke is less well
      understood, we sought to determine whether thrombocytopenia at admission for
      acute ischemic stroke was associated with in-hospital mortality. METHODS: We used
      data from a retrospective cohort of stroke patients (1998-2003) at 5 U.S.
      hospitals. Risk factors considered included conditions that can lead to
      thrombocytopenia (e.g., liver disease), increase bleeding risk (e.g.,
      hemophilia), medications with antiplatelet effects (e.g., aspirin), and known
      predictors of mortality (e.g., National Institutes of Health Stroke Scale and
      Charlson Comorbidity Index scores). Logistic regression modeling evaluated the
      adjusted association between thrombocytopenia, defined as platelets <100,000/MUL,
      and in-hospital mortality. RESULTS: Among 1233 acute ischemic stroke patients,
      thrombocytopenia was present in 2.3% (n = 28). A total of 6.1% (n = 75) of
      patients died in the hospital. In unadjusted analyses, thrombocytopenia was
      associated with higher mortality (8/28 [28.6%] v 67/1205 [5.6%]; P < .0001).
      Thrombocytopenia was also independently associated with in-hospital mortality
      after adjustment for National Institutes of Health Stroke Scale score and
      comorbidities, with an odds ratio of 6.6 (95% confidence interval 2.3-18.6).
      CONCLUSIONS: Admission thrombocytopenia among patients presenting with acute
      ischemic stroke predicts in-hospital mortality.

PMID- 22974704
TI  - Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.
AB  - Although a previous or recent history of varicella-zoster virus (VZV) infection
      is known to increase the risk of stroke in both children and adults, the
      influence of zoster sine herpetic remains unclear. We report an immunocompetent
      man with common cold symptoms and conjunctivitis, followed by an acute onset of
      bulbar weakness and hemihypesthesia without preceding skin rash. Acute medullary
      infarction and left vertebral artery stenosis were detected. VZV infection was
      finally identified. Zoster sine herpetic interferes with accurate diagnosis of
      infectious stroke, and vertebral artery involvement is unusual in ischemic stroke
      in this situation. An unexplained course of ischemic stroke event should be
      suspected in patients with VZV cerebrovasculopathy, especially in those without
      conventional stroke risk factors and those exhibiting concomitant infectious
      complications.

PMID- 22974705
TI  - Pig oocyte vitrification by Cryotop method and the activation of the apoptotic
      cascade.
AB  - Oocyte and embryo cryopreservation has been applied successfully in many
      mammalian species. Nevertheless, pig oocytes, because of their greater
      susceptibility to cryoinjuries, have shown a reduced ability to be fertilized in
      vitro and a lower developmental competence. The aim of this study was to evaluate
      the apoptotic status of porcine oocytes vitrified by Cryotop method. We assessed
      three parameters linked to the activation of the apoptotic cascade: the
      exteriorization of phosphatidylserine using Annexin V, the caspase activation
      using FITC-VAD-FMK and the alteration of plasma membrane permeability employing
      YO-PRO-1. These assays were performed on control oocytes, oocytes exposed to
      vitrification solutions (toxicity control) and vitrified oocytes either
      immediately after warming or after incubation for 2h into maturation medium. The
      exposition to vitrification solutions triggered an increase of the percentage of
      oocytes both faintly (VAD+ PI-) and strongly (VAD++ PI-) labeled by FITC-VAD-FMK
      but not a significant modification of the number of oocytes Annexin V (A+ PI-,
      early apoptotic) and YO-PRO-1(YP+ PI-, apoptotic) positive in comparison with
      control oocytes. Oocytes submitted to the whole vitrification procedure showed a
      rise of the percentage of early apoptotic oocytes (A+ PI-) and FITC-VAD-FMK
      positive oocytes (VAD+/VAD++ PI-) and a contemporaneous increase of the number of
      dead oocytes (PI+). On the contrary, vitrified oocytes analyzed immediately after
      warming did not show a significant increase in the percentage of apoptotic
      oocytes (YO-PRO-1+/PI-) as compared with the control. Post warming incubation for
      2h into maturation medium, in comparison with oocytes analyzed immediately after
      warming, did not induce any increase in the percentage of early apoptotic (A+ P-)
      oocytes while a decrease of the percentage of VAD+/PI- oocytes and a
      contemporaneous increase of VAD-/PI- oocytes were observed. Moreover, the post
      warming incubation induced a rise of the percentage of apoptotic oocytes (YO-PRO
      1+/PI-). All these data confirm the involvement of apoptotic mechanisms on the
      injuries induced by vitrification procedure in pig oocytes; explanation of this
      phenomenon could be useful to improve oocytes' cryopreservation protocols.

PMID- 22974706
TI  - Proliferation of seminiferous epithelium cells during the postnatal development
      in goats.
AB  - The objective of this research study was to evaluate the proliferation of somatic
      and germ cells in the seminiferous epithelium of Alpine goats. A total of 47
      goats reared in semi-intensive conditions were used, divided into age groups from
      birth up to 12 months of age. Following castration, testis fragments were
      included in plastic resin and were mounted in Entellan((r)) for histometric
      evaluations. In general, the total number of germ cells per seminiferous cord
      transverse section was low until 4 months of age. An increase was observed
      between 4 and 5 months, lasting until 9 months of age. From that age on, this
      number tended to stabilize, until 12 months. The population of support cells
      (undifferentiated support cells and Sertoli cells) remained constant from birth
      to the first month, when it peaked. This was followed by a reduction until the
      fifth month of age. From that age on, there was differentiation in mature Sertoli
      cells, and its population remained constant until 12 months of age. It can be
      concluded that Alpine goats were in the impuberal phase from birth to 3 months of
      age, prepuberal phase during the fourth month, reached puberty at 5 months of
      age, postpuberal phase from 6 to 8 months, and reached sexual maturity at 9
      months of age. Overall yield of spermatogenesis and Sertoli cell index increased
      from puberty up to the 12th month of age.

PMID- 22974707
TI  - Effects of Taurine or Trehalose supplementation on functional competence of
      cryopreserved Karan Fries semen.
AB  - Cryopreserved semen is commonly used for assisted reproduction in livestock
      including cattle. However, spermatozoa undergo numerous physiological and
      biochemical changes during freezing and thawing process that affects their
      fertilizing ability. The aim of present study was to improve the post thaw
      quality of crossbreed cattle "Karan Fries" (Holstein-Friesian*Tharparkar)
      spermatozoa. A total of nine ejaculates from three randomly chosen Karan Fries
      bulls were extended and cryopreserved in Tris-egg yolk citrate (EYTC) extender
      supplemented with 50mM Taurine or 100mM Trehalose. Semen samples cryopreserved
      without these additives in EYTC extender were taken as a control. Cryopreserved
      semen were thawed and assessed for semen quality parameters like sperm motility,
      viability and plasma membrane integrity. Extent of capacitation was measured by
      estimating the number of sperm that underwent an acrosome reaction with
      Lysophosphatidyl choline (LPC) addition by dual staining with giemsa and trypan
      blue stains. Oxidative stress in terms of rate of H(2)O(2) production and
      membrane lipid peroxidation were assessed in spermatozoa. Intracellular calcium
      concentration was also measured using fluorescent dye Fura-2AM. Post-thaw semen
      evaluation showed that supplementation of Taurine or Trehalose to EYTC extender
      significantly (P<0.05) increased motility, viability and membrane integrity of
      spermatozoa. Percentage of cryocapacitated spermatozoa was also significantly
      (P<0.05) decreased in presence of these additives. Similarly, rate of H(2)O(2)
      production, lipid peroxidation and intracellular calcium were found to be
      significantly (P<0.05) higher in spermatozoa cryopreserved in absence of these
      additives. The results obtained clearly indicated that supplementation of Taurine
      or Trehalose to EYTC extender prior to cryopreservation improves Karan Fries
      sperm quality.

PMID- 22974709
TI  - Purinergic P2Y2 receptors promote neutrophil infiltration and hepatocyte death in
      mice with acute liver injury.
AB  - BACKGROUND & AIMS: During progression of liver disease, inflammation affects
      survival of hepatocytes. Endogenous release of adenosine triphosphate (ATP) in
      the liver activates purinergic P2 receptors (P2R), which regulate inflammatory
      responses, but little is known about the roles of these processes in the
      development of acute hepatitis. METHODS: We induced acute hepatitis in C57BL/6
      mice by intravenous injection of concanavalin A and then analyzed liver
      concentrations of ATP and expression of P2R. We assessed P2Y(2)R(-/-) mice and
      C57BL/6 wild-type mice injected with suramin, a pharmacologic inhibitor of P2YR.
      Toxic liver failure was induced in mice by intraperitoneal injection of
      acetaminophen. Hepatocyte-specific functions of P2R signaling were analyzed in
      primary mouse hepatocytes. RESULTS: Induction of acute hepatitis in wild-type
      C57BL/6 mice released large amounts of ATP from livers and induced expression of
      P2Y(2)R. Liver damage and necrosis were greatly reduced in P2Y(2)R(-/-) mice and
      C57BL/6 mice given injections of suramin. Acetaminophen-induced liver damage was
      reduced in P2Y(2)R(-/-) mice. Analysis of liver-infiltrating immune cells during
      acute hepatitis revealed that expression of P2Y(2)R in bone marrow-derived cells
      was required for liver infiltration by neutrophils and subsequent liver damage.
      Hepatic expression of P2Y(2)R interfered with expression of genes that regulate
      cell survival, and promoted tumor necrosis factor-alpha-mediated cell death, in a
      cell-autonomous manner. CONCLUSIONS: Extracellular ATP and P2Y(2)R have cell-type
      specific, but synergistic functions during liver damage that regulate cellular
      immune responses and promote hepatocyte death. Reagents designed to target
      P2Y(2)R might be developed to treat inflammatory liver disease.

PMID- 22974708
TI  - Notch signaling is activated in human hepatocellular carcinoma and induces tumor
      formation in mice.
AB  - BACKGROUND & AIMS: The Notch signaling pathway is activated in leukemia and solid
      tumors (such as lung cancer), but little is known about its role in liver cancer.
      METHODS: The intracellular domain of Notch was conditionally expressed in
      hepatoblasts and their progeny (hepatocytes and cholangiocytes) in mice. This was
      achieved through Cre expression under the control of an albumin and alpha
      fetoprotein (AFP) enhancer and promoter (AFP-Notch intracellular domain [NICD]).
      We used comparative functional genomics to integrate transcriptome data from AFP
      NICD mice and human hepatocellular carcinoma (HCC) samples (n = 683). A Notch
      gene signature was generated using the nearest template prediction method.
      RESULTS: AFP-NICD mice developed HCC with 100% penetrance when they were 12
      months old. Activation of Notch signaling correlated with activation of 3
      promoters of insulin-like growth factor 2; these processes appeared to contribute
      to hepatocarcinogenesis. Comparative functional genomic analysis identified a
      signature of Notch activation in 30% of HCC samples from patients. These samples
      had altered expression in Notch pathway genes and activation of insulin-like
      growth factor signaling, despite a low frequency of mutations in regions of
      NOTCH1 associated with cancer. Blocking Notch signaling in liver cancer cells
      with the Notch activation signature using gamma-secretase inhibitors or by
      expressing a dominant negative form of mastermind-like 1 reduced their
      proliferation in vitro. CONCLUSIONS: Notch signaling is activated in human HCC
      samples and promotes formation of liver tumors in mice. The Notch signature is a
      biomarker of response to Notch inhibition in vitro.

PMID- 22974710
TI  - Hyperthermia-induced micronucleus formation in a human keratinocyte cell line.
AB  - Elevated temperature can cause biological effects in vitro and in vivo. Many
      studies on effects of hypo- and hyperthermia have been conducted, but only few
      studies systematically investigated the formation of genomic damage in the
      micronucleus test in human cells in vitro as a consequence of different
      temperatures. In the present study, HaCaT human keratinocytes were exposed to
      different temperatures from 37 degrees C to 42 degrees C for 24h in a regular
      cell culture incubator. Micronucleus frequency as a marker of genomic damage was
      elevated in a temperature-dependent and statistically significant manner.
      Apoptosis occurred at temperatures of 39 degrees C or higher. Cell proliferation
      was unaffected up to 40 degrees C and decreased at 41 degrees C and 42 degrees C.
      Expression of the heat shock protein Hsp70 was elevated, particularly at
      temperatures of 40 degrees C and higher. These findings are in agreement with
      several in vivo studies and some in vitro studies looking at single, specific
      temperatures, but a systematically investigated temperature-dependent increase of
      genomic damage in human keratinocytes in vitro is demonstrated for the first time
      here.

PMID- 22974711
TI  - Computational screening and molecular dynamics simulation of disease associated
      nsSNPs in CENP-E.
AB  - Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors.
      Mutations in centroemere proteins have been observed in promoting aneuploidy and
      tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP
      E) is involved in inducing cancers. In this study we investigated the pathogenic
      effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point
      mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP,
      MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding
      affinity of ATP molecule to the CENP-E motor domain. Complementarity scores
      obtained from docking studies showed significant loss in ATP binding affinity of
      mutant structure. Molecular dynamics simulation was carried to examine the
      structural consequences of Y63H mutation. Root mean square deviation (RMSD), root
      mean square fluctuation (RMSF), radius of gyration (R(g)), solvent accessibility
      surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector
      projection, trace of covariance matrix and atom density analysis results showed
      notable loss in stability for mutant structure. Y63H mutation was also shown to
      disrupt the native conformation of ATP binding region in CENP-E motor domain.
      Docking studies for remaining 18 mutations at 63rd residue position as well as
      other two computationally predicted disease associated mutations S22L and P69S
      were also carried to investigate their affect on ATP binding affinity of CENP-E
      motor domain. Our study provided a promising computational methodology to study
      the tumorigenic consequences of nsSNPs that have not been characterized and clear
      clue to the wet lab scientist.

PMID- 22974712
TI  - Venom proteomes of South and North American opisthoglyphous (Colubridae and
      Dipsadidae) snake species: a preliminary approach to understanding their
      biological roles.
AB  - Opisthoglyphous snake venoms remain under-explored despite being promising
      sources for ecological, evolutionary and biomedical/biotechnological research.
      Herein, we compared the protein composition and enzymatic properties of the
      venoms of Philodryas baroni (PbV), Philodryas olfersii olfersii (PooV) and
      Philodryas patagoniensis (PpV) from South America, and Hypsiglena torquata texana
      (HttV) and Trimorphodon biscutatus lambda (TblV) from North America. All venoms
      degraded azocasein, and this metalloproteinase activity was significantly
      inhibited by EDTA. PooV exhibited the highest level of catalytic activity towards
      synthetic substrates for serine proteinases. All venoms hydrolyzed
      acetylthiocholine at low levels, and only TblV showed phospholipase A(2)
      activity. 1D and 2D SDS-PAGE profile comparisons demonstrated species-specific
      components as well as several shared components. Size exclusion chromatograms
      from the three Philodryas venoms and HttV were similar, but TblV showed a notably
      different pattern. MALDI-TOF MS of crude venoms revealed as many as 49 distinct
      protein masses, assigned to six protein families. MALDI-TOF/TOF MS analysis of
      tryptic peptides confirmed the presence of cysteine-rich secretory proteins in
      all venoms, as well as a phospholipase A(2) and a three-finger toxin in TblV.
      Broad patterns of protein composition appear to follow phylogenetic lines, with
      finer scale variation likely influenced by ecological factors such as diet and
      habitat.

PMID- 22974714
TI  - Discussion.

PMID- 22974713
TI  - Sutureless aortic valve replacement as an alternative treatment for patients
      belonging to the "gray zone" between transcatheter aortic valve implantation and
      conventional surgery: a propensity-matched, multicenter analysis.
AB  - OBJECTIVE: The aim of this propensity-matched, multicenter study was to compare
      early clinical and echocardiographic outcomes of patients undergoing transapical
      aortic valve implantation (TA-TAVI) versus patients undergoing sutureless aortic
      valve replacement (SU-AVR) for severe symptomatic aortic valve stenosis. METHODS:
      We reviewed 468 TA-TAVIs performed in 20 centers from April 2008 to May 2011, and
      51 SU-AVRs performed in 3 centers from March to September 2011. Based on a
      propensity score analysis, 2 groups with 38 matched pairs were created. Variables
      used in the propensity analysis were age, sex, body surface area, New York Heart
      Association class, logistic EuroSCORE, peripheral vascular disease, chronic
      obstructive pulmonary disease, aortic valve area, mitral regurgitation, and left
      ventricular ejection fraction. RESULTS: Preoperative characteristics of the 2
      groups were comparable. Hospital mortality was 5.3% and 0% in the TA-TAVI and SU
      AVR groups, respectively (P = .49). We did not observe stroke or acute myocardial
      infarction in the 2 groups. Permanent pacemaker implantation was needed in 2
      patients of each group (5.3%, P = 1.0). Dialysis was required in 2 patients
      (5.3%) in the SU-AVR group and in 1 patient (2.7%) in the TA-TAVI group (P =
      1.0). Predischarge echocardiographic data showed that the incidence of
      paravalvular leak (at least mild) was greater in the TA-TAVI group (44.7% vs
      15.8%, P = .001), but there were no differences in terms of mean transprosthetic
      gradient (10.3 +/- 5 mm Hg vs 11 +/- 3.7 mm Hg, P = .59). CONCLUSIONS: This
      preliminary experience showed that, in patients at high risk for conventional
      surgery, SU-AVR is as safe and effective as TA-TAVI and that it is associated
      with a lower rate of postprocedural paravalvular leak.

PMID- 22974715
TI  - Ultralow liquid/solid friction in carbon nanotubes: comprehensive theory for
      alcohols, alkanes, OMCTS, and water.
AB  - In this work, we perform a theoretical study of liquid flow in graphitic
      nanopores of different sizes and geometries. Molecular dynamics flow simulations
      of different liquids (water, decane, ethanol, and OMCTS) in carbon nanotubes
      (CNT) are shown to exhibit flow velocities 1-3 orders of magnitude higher than
      those predicted from the continuum hydrodynamics framework and the no-slip
      boundary condition. These results support previous experimental findings obtained
      by several groups that reported exceptionally high liquid flow rates in CNT
      membranes. The liquid/graphite friction coefficient is identified as the crucial
      parameter for this fast mass transport in CNT. The friction coefficient is found
      to be very sensitive to wall curvature: friction is independent of confinement
      for liquids between flat graphene walls with zero curvature, whereas it decreases
      with increasing positive curvature (liquid inside CNT), and it increases with
      increasing negative curvature (liquid outside CNT). Furthermore, we present a
      theoretical approximate expression for the friction coefficient, which predicts
      qualitatively and semiquantitatively its curvature dependent behavior. The
      proposed theoretical description, which works well for different kinds of liquids
      (alcohols, alkanes, and water), sheds light on the physical mechanisms at the
      origin of the ultra low liquid/solid friction in CNT. In fact, it is due to their
      perfectly ordered molecular structure and their atomically smooth surface that
      carbon nanotubes are quasiperfect liquid conductors compared to other membrane
      pores like nanochannels in amorphous silica.

PMID- 22974716
TI  - Fractional urinary fluoride excretion of 6-7-year-old children attending schools
      in low-fluoride and naturally fluoridated areas in the UK.
AB  - F is an important trace element for bones and teeth. The protective effect of F
      against dental caries is well established. Urine is the prime vehicle for the
      excretion of F from the body; however, the relationship between F intake and
      excretion is complex: the derived fractional urinary F excretion (FUFE) aids
      understanding of this in different age groups. The present study aimed to
      investigate the relationships between (1) total daily F intake (TDFI) and daily
      urinary F excretion (DUFE), and (2) TDFI and FUFE in 6-7-year-olds, recruited in
      low-F and naturally fluoridated (natural-F) areas in north-east England. TDFI
      from diet and toothbrushing and DUFE were assessed through F analysis of
      duplicate dietary plate, toothbrushing expectorate and urine samples using a F
      ion-selective electrode. FUFE was calculated as the ratio between DUFE and TDFI.
      Pearson's correlation and regression analysis were used to investigate the
      relationship between TDFI and FUFE. A group of thirty-three children completed
      the study; twenty-one receiving low-F water (0.30 mg F/l) and twelve receiving
      natural-F water (1.06 mg F/l) at school. The mean TDFI was 0.076 (SD 0.038) and
      0.038 (SD 0.027) mg/kg per d for the natural-F and low-F groups, respectively.
      The mean DUFE was 0.017 (SD 0.007) and 0.012 (SD 0.006) mg/kg per d for the
      natural-F and low-F groups, respectively. FUFE was lower in the natural-F group
      (30 %) compared with the low-F group (40 %). Pearson's correlation coefficient
      for (1) TDFI and DUFE was +0.22 (P= 0.22) and for (2) TDFI and FUFE was - 0.63
      (P< 0.001). In conclusion, there was no correlation between TDFI and DUFE.
      However, there was a statistically significant negative correlation between FUFE
      and TDFI.

PMID- 22974717
TI  - Significant improvement in superselective intra-arterial chemotherapy for oral
      cancer by using indocyanine green fluorescence.
AB  - BACKGROUND: Recent advances in indocyanine green (ICG) fluorescence imaging have
      enabled the visualization of the blood supply to tissues. For advanced head and
      neck cancer, intra-arterial chemotherapy has been applied for organ preservation
      and improvement of the prognosis. To identify the tumor-feeding artery, through
      which the intra-arterial chemotherapy should be administered, CT angiography has
      been shown to be useful. However, the precise evaluation for oral cancer patients
      depends on the oral environment, that is, whether they have been treated with
      dental metal. OBJECTIVES: To assess the feasibility of the ICG fluorescence
      technique during intra-arterial chemotherapy for advanced oral cancer. MATERIAL
      AND METHOD: Twenty-five patients with oral cancer who were treated by intra
      arterial chemotherapy were included in this study. Conventional CT angiography
      followed by 5mg of ICG injection was performed to confirm the areas in which the
      drug had dispersed. Intra-arterial chemotherapy was administered at 75 mg/m(2) of
      CDDP. Additional information about the arteries feeding the tumors provided by
      ICG was evaluated. RESULTS: Out of 25 cases, in 15 (56%) the blood supply to the
      cancer was clearly detected by CT angiography. Using the infrared ICG evaluation,
      the blood supply to the tumor was confirmed easily in all cases. The information
      obtained from fluorescence imaging was helpful for making decisions concerning
      the administration of chemo-agents for oral cancers. CONCLUSION: ICG fluorescence
      imaging during intra-arterial chemotherapy compensated for the deficiencies of CT
      angiography, especially for oral cancer. ICG fluorescence provided us clearer and
      more useful information about the feeders to tumors.

PMID- 22974718
TI  - Perceived instrumental support and children's health across the early life
      course.
AB  - A large, venerable literature demonstrates the importance of social relationships
      and social support for health, though much less research examines whether the
      benefits of social support to mothers extend to children. This paper examines the
      relationship between mothers' perceptions of instrumental support and children's
      health using longitudinal data from the U.S. Fragile Families and Child Wellbeing
      Study (N = 4342), a cohort of American children born in urban areas to mostly
      unmarried parents. Results suggest mothers' perceptions of instrumental support
      is positively associated with children's overall health, and this finding
      persists despite controlling for a host of individual-level characteristics of
      mothers and children (including a lagged indicator of children's health) and in
      fixed-effect models. Mothers' economic security and mothers' wellbeing attenuate
      some, but not all, of the association between perceived instrumental support and
      children's overall health. In addition, the link between perceived instrumental
      support and three specific indicators of health - asthma, overweight/obese, and
      number of emergency room visits - falls to statistical insignificance after
      accounting for individual-level characteristics, suggesting these associations
      result from social selection processes. Taken together, these findings suggest
      the beneficial health consequences of social support may extend to children
      across the early life course and demonstrate the need to better understand
      mothers' reports of children's overall health. 

PMID- 22974719
TI  - Medicalization and pharmaceuticalization at the intersections: a commentary on
      Bell and Figert (2012).

PMID- 22974720
TI  - Mannose-binding lectin gene polymorphisms are not associated with susceptibility
      to severe early childhood caries.
AB  - Our purpose was to investigate a possible relationship between severe early
      childhood caries (S-ECC) and polymorphism of the mannose binding lectin gene and
      investigate the role of allele variant as a possible factor in the susceptibility
      to S-ECC. Sixty-two Chinese children with S-ECC and 68 caries-free control
      children were included in this study. Genomic DNA was extracted from buccal
      epithelial cells of each individual. The identification of MBL B allele was
      performed by restriction fragment length polymorphism using Ban I restriction
      enzyme. The frequency of MBL mutant genotype (GGC/GAC and GAC/GAC) was more
      frequent among children with S-ECC compared with control groups, but did not
      significantly differ between two groups (x(2) = 2.82, p > 0.05). There was no
      significant difference in the allele frequency of codon54 wild type (allele A)
      between two groups (x(2) = 2.76, p > 0.05). The present study did not find
      evidence of MBL codon54 polymorphisms being associated with S-ECC in the
      population studied, but a larger sample size is necessary to confirm the present
      results.

PMID- 22974721
TI  - Assessment and validation of groundwater vulnerability to nitrate based on a
      modified DRASTIC model: a case study in Jilin City of northeast China.
AB  - The assessment of groundwater vulnerability to pollution has become a useful tool
      for groundwater pollution prevention and control. Following the theory of overlay
      index method and with the aid of GIS technique and a statistical method, this
      study employed a modified DRASTIC model to assess the groundwater vulnerability
      to nitrate in Jilin City of northeast China. In order to reduce the subjectivity
      of the overlay index method, the model was optimized by rebuilding the index
      system, adjusting the rating scale of each index, reassigning the index weights
      and comparing grading methods for groundwater vulnerability to nitrate. The
      criteria for these optimizations were the correlation coefficient of each index
      with the nitrate concentration in groundwater. Net recharge (R), soil type (S),
      impact of vadose zone (I), groundwater velocity (V) and land use type (L) were
      picked up to compose the index system. And then the accuracy of vulnerability
      mapping was discussed by a group of integrated indicators, including the
      corresponding relationship between the extreme nitrate concentration and the
      vulnerability classes, F statistic and class difference between the groundwater
      vulnerability classification and concentration classification of NO(3)-N. The
      optimized model graded by geometrical interval method improved the correlation
      between vulnerability index and nitrate concentration to the order of 0.6698
      which was 0.4098 higher than that by the DRASTIC model. By level difference
      calculation, the correct vulnerability regions accounted for 64.45% of the study
      area. Lastly, sensitivity analyses indicated that the soil media and groundwater
      velocity were the most critical factors affecting groundwater vulnerability to
      nitrate. In short, RSIVL model was suitable to assess the groundwater
      vulnerability to nitrate in the study area with readily available hydrogeological
      and hydrochemical data. Hence, the mapping of groundwater vulnerability to
      nitrate can be applied for sensible groundwater resource management and land use
      planning.

PMID- 22974722
TI  - Neuro-protective effects of bee venom by suppression of neuroinflammatory
      responses in a mouse model of Parkinson's disease: role of regulatory T cells.
AB  - In the present study, we sought to determine whether bee venom (BV) promotes the
      survival of dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Treatment with
      BV prevented degeneration of DA neurons in the substantia nigra (SN). This neuro
      protective effect of BV was associated with microglial deactivation and reduction
      of CD4 T cell infiltration. Additionally, BV treatment significantly increased
      the proportion of CD4(+)CD25(+)Foxp3(+) Tregs in vivo and in vitro. The increased
      proportion of Tregs by BV treatment remained suppressive ex vivo. Interestingly,
      BV treatment did not prevent MPTP neurotoxicity in mice depleted of Tregs by anti
      CD25 antibody injection. Therefore, our present studies suggest that modulation
      of peripheral immune tolerance by Treg may contribute to the neuroprotective
      effect of BV in the MPTP model of Parkinson's disease.

PMID- 22974723
TI  - Synthesis of annulated arenes and heteroarenes involving Lewis acid-mediated
      regioselective annulation of unsymmetrical 1,2
      (diaryl/diheteroarylmethine)dipivalates.
AB  - A ZnBr(2)-mediated regioselective annulation of unsymmetrical 1,2
      diarylmethinedipivalates in DCM at room temperature led to the formation of
      annulated arenes and heteroarenes. The annulation of the dipivalate proceeds
      through the intermediacy of benzylic carbocations followed by intramolecular
      cyclization and subsequent aromatization to give the annulated products. The
      annulation methodology is highly efficient for the syntheses of anthracene as
      well as naphtho[b]thiophene analogues.

PMID- 22974725
TI  - Dual anti-platelet therapy in patients with G6PD deficiency after percutaneous
      coronary intervention.

PMID- 22974724
TI  - Structure-guided engineering of Lactococcus lactis alcohol dehydrogenase LlAdhA
      for improved conversion of isobutyraldehyde to isobutanol.
AB  - We have determined the X-ray crystal structures of the NADH-dependent alcohol
      dehydrogenase LlAdhA from Lactococcus lactis and its laboratory-evolved variant
      LlAdhA(RE1) at 1.9A and 2.5A resolution, respectively. LlAdhA(RE1), which
      contains three amino acid mutations (Y50F, I212T, and L264V), was engineered to
      increase the microbial production of isobutanol (2-methylpropan-1-ol) from
      isobutyraldehyde (2-methylpropanal). Structural comparison of LlAdhA and
      LlAdhA(RE1) indicates that the enhanced activity on isobutyraldehyde stems from
      increases in the protein's active site size, hydrophobicity, and substrate
      access. Further structure-guided mutagenesis generated a quadruple mutant
      (Y50F/N110S/I212T/L264V), whose KM for isobutyraldehyde is ~17-fold lower and
      catalytic efficiency (kcat/KM) is ~160-fold higher than wild-type LlAdhA.
      Combining detailed structural information and directed evolution, we have
      achieved significant improvements in non-native alcohol dehydrogenase activity
      that will facilitate the production of next-generation fuels such as isobutanol
      from renewable resources.

PMID- 22974726
TI  - Dexamethasone-eluting stents had sustained favorable ischemic driven target
      lesion revascularization rates over 5 years: a randomized controlled prospective
      study.

PMID- 22974727
TI  - Allostatic overload in patients with atrial fibrillation.

PMID- 22974728
TI  - Besides CYP2C19, PON1 genetic variant influences post-clopidogrel platelet
      reactivity in Chinese patients.

PMID- 22974729
TI  - Recurrent Tako-Tsubo cardiomyopathy apparently induced by opposite triggers.

PMID- 22974730
TI  - The relationship between heart and stomach in Iranian traditional medicine: a new
      concept in cardiovascular disease management.

PMID- 22974731
TI  - Abnormal muscle vascular responses during exercise in myocardial infarction
      patients.

PMID- 22974732
TI  - Biological efficacy and clinical safety of a second 600 mg loading dose of
      clopidogrel in elderly patients with high on-treatment platelet reactivity: a
      pilot study.

PMID- 22974733
TI  - Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment
      and amyloid deposition in APP/PS1 mice.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by
      extracellular Abeta(1-42) containing plaques, and intracellular neurofibrillary
      tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory
      deficits and cognitive disabilities start to occur as these hallmarks affect
      hippocampus and frontal cortex, regions highly involved in memory. Connective
      tissue growth factor (CTGF) expression, which is high in the vicinity of Abeta
      plaques and NFTs, was found to influence gamma-secretase activity, the molecular
      crux in Abeta(1-42) production. Tauroursodeoxycholic acid (TUDCA) is an
      endogenous bile acid that downregulates CTGF expression in hepatocytes and has
      been shown to possess therapeutic efficacy in neurodegenerative models. To
      investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4%
      TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six
      months of TUDCA supplementation prevented the spatial, recognition and contextual
      memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA
      supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid
      deposition. These effects of TUDCA supplementation suggest a novel mechanistic
      route for Alzheimer therapeutics.

PMID- 22974735
TI  - Human environments: definition, scope, and the role of toxicology.
AB  - This chapter is a brief introduction to the subject matter of the volume
      including the complexity and definition of human environments. Exposure to
      complex mixtures and the problem of interactions are considered as well as the
      important role of toxicology in environmental and human health, including risk
      analysis, risk management, and risk communication.

PMID- 22974736
TI  - Estimating human exposure: improving accuracy with chemical markers.
AB  - Exposure to chemicals, natural as well as anthropogenic, occurs in the human
      environment. In the absence of chemical-specific data for the wide variety of
      exposure scenarios, federal agencies have adopted two approaches to estimating
      exposures. The first is to set chemical standards for exposures, usually through
      a single route. These standards are set based on risk assessment principles and
      economic feasibility. When there are standards, measurement of environmental
      chemical concentrations can be used to prevent unacceptable levels of exposure.
      The second approach is to estimate external exposure (typically route-specific)
      and/or an absorbed dose using a series of assumptions regarding translation of
      chemical concentrations from one part of the environment to another, human
      activity patterns, and chemical absorption through various routes into the body.
      These assumptions have been converted into algorithms that can be used to
      estimate a human exposure and dosage, typically expressed on body weight basis.
      These algorithms, designed to avoid underestimations of human exposure, have, in
      some instances, been incorporated into computer models. Chemical markers,
      measured either as the parent compound or as metabolites in human populations
      with known exposure to the parent compound, can be applied to improve the
      accuracy of these estimates of exposure.

PMID- 22974734
TI  - hMTH1 expression protects mitochondria from Huntington's disease-like impairment.
AB  - Huntington disease (HD) is a neurodegenerative disease caused by expansion of CAG
      repeats in the huntingtin (Htt) gene. The expression of hMTH1, the human
      hydrolase that degrades oxidized purine nucleoside triphosphates, grants
      protection in a chemical HD mouse model in which HD-like features are induced by
      the mitochondrial toxin 3-nitropropionic acid (3-NP). To further examine the
      relationship between oxidized dNTPs and HD-like neurodegeneration, we studied the
      effects of hMTH1 expression in a genetic cellular model for HD, such as striatal
      cells expressing mutant htt (Hdh(Q111)). hMTH1 expression protected these cells
      from 3-NP and H2O2-induced killing, by counteracting the mutant htt-dependent
      increased vulnerability and accumulation of nuclear and mitochondrial DNA 8
      hydroxyguanine levels. hMTH1 expression reverted the decreased mitochondrial
      membrane potential characteristic of Hdh(Q111) cells and delayed the increase in
      mitochondrial reactive oxygen species associated with 3-NP treatment. Further
      indications of hMTH1-mediated mitochondrial protection are the partial reversion
      of 3-NP-induced alterations in mitochondrial morphology and the modulation of
      DRP1 and MFN1 proteins, which control fusion/fission rates of mitochondria.
      Finally, in line with the in vitro findings, upon 3-NP in vivo treatment, 8
      hydroxyguanine levels in mitochondrial DNA from heart, muscle and brain are
      significantly lower in transgenic hMTH1-expressing mice than in wild-type
      animals. 

PMID- 22974737
TI  - Metabolism of xenobiotics of human environments.
AB  - Xenobiotics have been defined as chemicals to which an organism is exposed that
      are extrinsic to the normal metabolism of that organism. Without metabolism, many
      xenobiotics would reach toxic concentrations. Most metabolic activity inside the
      cell requires energy, cofactors, and enzymes in order to occur. Xenobiotic
      metabolizing enzymes can be divided into phase I, phase II, and transporter
      enzymes. Lipophilic xenobiotics are often first metabolized by phase I enzymes,
      which function to make xenobiotics more polar and provide sites for conjugation
      reactions. Phase II enzymes are conjugating enzymes and can directly interact
      with xenobiotics but more commonly interact with metabolites produced by phase I
      enzymes. Through both passive and active transport, these more polar metabolites
      are eliminated. Most xenobiotics are cleared through multiple enzymes and
      pathways. The relationship between chemical concentrations, enzyme affinity and
      quantity, and cofactor availability often determine which metabolic reactions
      dominate in a given individual.

PMID- 22974738
TI  - Toxic endpoints in the study of human exposure to environmental chemicals.
AB  - Human exposure to chemicals in the environment can occur in an acute or chronic
      manner causing toxicity to different organs or resulting in other adverse health
      effects. To assess if chemicals encountered by humans in different environments
      have the potential to be toxic, both in vitro and in vivo testing models can be
      utilized and will be discussed in this chapter. The structures and function of
      different organs of the body often predispose these organs to being especially
      sensitive to chemical exposures. Specificity, a general description of endpoints
      of toxic action will be discussed in relation to carcinogenesis, hepatotoxicity,
      renal toxicity, neurotoxicity, reproductive toxicity, endocrine toxicity, and
      immunotoxicity. Examples of environmental chemicals causing toxicity will be
      provided, and endpoints will be discussed ranging from histopathological
      characteristics to gene expression profiling.

PMID- 22974739
TI  - Pesticide regulations: exposure-dose modeling from FIFRA to FQPA.
AB  - The federal laws and regulations governing the registration and use of pesticides
      in the United States under the Federal Insecticide, Fungicide, and Rodenticide
      Act are published in the Federal Register, while state laws such as California
      are published in the California Food and Agricultural Code, Divisions 6, 7, and
      13. Up until the passage of the Food Quality Protection Act (FQPA of 1996),
      federal and state regulations pertaining to the registration and use of
      pesticides were in most cases identical except for the fact that food tolerances
      were enforced but not set at the state level. The California Department of
      Pesticide Regulation's Worker Health and Safety Program continues to monitor
      worker exposure to pesticides and report illnesses among workers associated with
      pesticide exposure. Under FQPA, the United States Environmental Protection Agency
      (EPA) has taken a leadership role in the development of probabilistic pesticide
      exposure models (i.e., DEEM, SHEDS, etc.) using pesticide application, human
      activity, and exposure databases (i.e., CPPAES, CHAD, CSFII, FCID, NHANES, and
      NHEXAS). A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD)
      modeling framework has been established by EPA to assess cumulative risk of dose
      and injury to infants and children to organophosphorus, carbamate (NMC), and
      pyrethroid insecticides from aggregate sources and routes. Probabilistic models
      are being linked to PBPK/PD models to improve risk assessments.

PMID- 22974740
TI  - Occupational chemicals: metabolism, toxicity, and mode of action.
AB  - Workers experience large interindividual variability in exposure and biological
      response following exposure to chemicals. Quantitative methods to investigate
      occupational exposures and their relationship with biomarker levels,
      toxicokinetics of chemicals, and gene-environment interactions in disease
      development can be performed to unlock the black-box paradigm in exposure-disease
      associations. Exposure to a chemical at work is generally greater than that
      experienced in the wider environment. While inhalation exposure has traditionally
      been the main focus in exposure assessment, there is growing awareness of the
      significance of contact and uptake of chemicals through dermal and ingestion
      routes. Biological monitoring can provide information on exposure and uptake of a
      chemical, biological response to exposure, early subclinical changes, and
      susceptibility for disease. Thus, biomarkers can provide an important link
      between exposure and disease and may be an important tool for risk assessment.
      Integration of toxicology with exposure assessment, dose-response, and
      toxicogenomics can be used to improve one's understanding of exposure-disease
      relationships and shape risk assessment strategies to protect worker health.

PMID- 22974741
TI  - Chemicals of military deployments: revisiting Gulf War Syndrome in light of new
      information.
AB  - Despite the amount of hard work that has gone into elucidating a toxicological
      basis for Gulf War Illness, we do not appear to have reached a mechanistic
      understanding. Investigation of long-term low-level exposure as a basis does not
      seem to have provided an answer. Nor does the deployment-related toxic soup idea,
      where exposure to a mixture of toxic chemicals not usually encountered in the
      same physical vicinity, seems to have explained the symptoms developed by Gulf
      War Veterans. The idea that an overabundance of CNS acetylcholine leftover from
      excessive cholinesterase inhibition is at the basis of this syndrome is
      intellectually appealing and offers a level of neurochemical complexity that may
      be just beyond the reach of our technical understanding. But no one has yet
      assembled a coherent mechanism from it either. It seems reasonable that chemical
      warfare agents were involved. They were not included in early work because it was
      felt that the toxicant plumes produced during the destruction of stockpiled Iraqi
      chemical weapons had not been large enough to cause an exposure of US forces and
      those of our allies. That misconception was disproven, and it is now accepted
      that people could very well have been exposed to low levels of massive quantities
      of sarin, cyclosarin, and sulfur mustard. It also seems reasonable that excess
      acetylcholine or neurological consequences of its presence that we do not fully
      understand were involved. The combination of nerve agents and the insecticidal
      anticholinesterases plus the pyridostigmine bromide given prophylactically were
      probably sufficient to cause the problem. However, the most notable thing is the
      result of recent work on the toxic mechanism of sulfur mustard showing that it
      can inhibit the microsomal electron transport chain as a result of sulfonium ion
      reduction to carbon free radicals by NADPH-cytochrome P450 reductase. This
      information was not available during the work on Gulf War Illness. So this
      provides an opportunity to discuss the effects of the general inhibition of the
      cytochrome P450 system superimposed on the conditions encountered by the
      participants in Desert Storm and Desert Shield as an approach to the toxicology
      of mixtures.

PMID- 22974742
TI  - Pharmaceuticals in the environment: lessons learned for reducing uncertainties in
      environmental risk assessment.
AB  - Pharmaceuticals in the environment are often present at trace levels (e.g., ng/L)
      in surface waters and effluents of developed countries, yet represent
      contaminants of emerging concern. Attributes of many of these substances, such as
      potency, chirality, and ionization, present challenges to historical
      environmental risk assessment and management paradigms. In this chapter, we
      critically examine several important aspects of pharmaceuticals, specifically
      highlighting some of the lessons we have learned from studying these substances
      in the environment over the past 15 years. We submit that incorporating such
      "lessons learned" during environmental risk assessments promises to reduce
      uncertainties and support more sustainable management efforts.

PMID- 22974743
TI  - Quantitative risk assessment methods for cancer and noncancer effects.
AB  - Human health risk assessments have evolved from the more qualitative approaches
      to more quantitative approaches in the past decade. This has been facilitated by
      the improvement in computer hardware and software capability and novel
      computational approaches being slowly recognized by regulatory agencies. These
      events have helped reduce the reliance on experimental animals as well as better
      utilization of published animal toxicology data in deriving quantitative toxicity
      indices that may be useful for risk management purposes. This chapter briefly
      describes some of the approaches as described in the guidance documents from
      several of the regulatory agencies as it pertains to hazard identification and
      dose-response assessment of a chemical. These approaches are contrasted with more
      novel computational approaches that provide a better grasp of the uncertainty
      often associated with chemical risk assessments.

PMID- 22974744
TI  - Human health risk assessment for contaminated properties.
AB  - Contaminated sites, particularly Superfund sites, not only require remediation
      but also require health risk analysis of the unremediated site. In this chapter,
      the term risk refers to the probability and the magnitude of adverse human health
      effects due to the unintended exposure to chemicals at sites that are
      contaminated or perceived to be contaminated. The quantitative estimation of this
      risk, the application to define how clean is clean, and the techniques available
      to mitigate and manage the risk are discussed: Estimation of exposure or dose and
      the uncertainties inherent in the calculations Quantitative chemical-specific
      measures of human toxicity of chemicals used in the RA process The metrics used
      to estimate the carcinogenic and noncarcinogenic risk Risk management and the
      concepts of acceptable risk Risk assessment and risk management of contaminated
      sites

PMID- 22974745
TI  - The future of human health risk assessment of environmental chemicals.
AB  - Dramatic changes are beginning to take place in risk assessment, changes that
      will involve rapid, high-throughput assays capable of analyzing large numbers of
      samples in a short time. These new systems will incorporate many of the aspects
      of cellular and molecular biology, including human and human-derived cell lines,
      toxicogenomics, proteomics, and metabolomics. The large amount of data generated
      will require a systems biology approach if it is to be reduced to generalizations
      of value in risk management. The current chapter briefly describes the emerging
      systems and their component parts.

PMID- 22974746
TI  - Ecological risk assessment.
AB  - Ecological risk assessment (ERA) has matured since the 1970s when it began as
      ecological assessment. ERA has its foundations in human health risk assessment,
      and as such, similarities exist between the two processes. However, the inherent
      complex nature of the ecosystem and its interwoven processes make the practice
      typically more complex for ERA than for human health risk assessment. In the
      early 1990s, the Environmental Protection Agency and others issued guidance
      documents that present a basic framework approach for conducting ERAs. This basic
      framework persists today and includes the three main components of the risk
      assessment process: problem formulation, analysis, and risk characterization.
      Over time, scientists, risk analysts, and risk managers have augmented the
      component steps with iterative feedbacks and a weight-of-evidence approach that
      integrates numerous lines of evidence for analyzing stressor effects, exposure
      likelihood, and ecosystem risks. This chapter aims to present the reader with an
      overview and examples of the current ERA process.

PMID- 22974747
TI  - Metabolic interactions of environmental toxicants in humans.
AB  - A description of the interactions between environmental toxicants following
      simultaneous exposure or exposure in close temporal sequence is presented. At the
      metabolic level, such interactions may be based on induction, inhibition, or
      activation of xenobiotic-metabolizing enzymes. Cytotoxicity may also play a role,
      particularly in affecting induction of xenobiotic-metabolizing enzymes. The
      effects of interactions manifested at the level of the expression of toxic
      endpoints may result from interactions at the metabolic level or may have other
      causes. New approaches to genome-wide effects (e.g., microarray studies) are also
      discussed.

PMID- 22974748
TI  - Toxins and venoms.
AB  - Toxins are produced by numerous microorganisms and invertebrates as well as by
      higher plants and animals. Venoms are produced by many groups of animals, from
      coelenterates to vertebrates. While toxins and venoms are the primary
      toxicological concern in natural ecosystems, they are frequently of importance in
      agroecosystems and in military deployments. They belong to a very large number of
      chemical classes and consequently are usually classified according to the groups
      of organisms producing them, for example, mycotoxins, algal toxins, and insect
      venoms. Plant toxins are representative of a larger group of phytochemicals known
      as secondary plant chemicals or plant allelochemicals. They may be acutely toxic,
      have chronic toxicity, or may be toxic at one dose but therapeutic at a lower
      dose. Some drugs of abuse are plant toxins abuse. A representative selection of
      the more important members of each category is provided.

PMID- 22974749
TI  - Summary and conclusions.
AB  - The complexity and interrelationships of human environments are constantly
      undergoing further definition. The importance of such definition can be realized
      when such broad environmental categories as natural ecosystems, the
      agroecosystem, occupational, urban, domestic, and military deployments, all of
      which can be subdivided into more specialized environments, are considered. Set
      against this background, it is clear that the principal role of toxicology is
      risk analysis. Risk analysis consists not only of risk assessment but also risk
      management and risk communication. New paradigms in hazard assessment are
      revolutionizing risk assessment, and all aspects, from molecular toxicology to
      outreach programs, will be involved in future considerations of human
      environments.

PMID- 22974750
TI  - Preface.

PMID- 22974751
TI  - Flavour preferences conditioned by protein solutions in post-weaning pigs.
AB  - Prior studies report in various mammalian species that a neutral flavour can
      become strongly preferred after being associated with a positive consequence of
      its consumption. Two experiments were performed to study flavour preferences
      conditioned by a protein source in weaned pigs. In experiment 1, pigs were
      trained to drink (30 min/day) one flavour (CS+) mixed into a 2% protein solution
      (Soybean Protein Concentrate; SPC or Porcine Digestible Peptides; PDP) and
      another flavour (CS-) mixed into water during 6 alternate sessions. The pigs in
      the SPC and PDP groups consumed more CS+ than CS- in the two-choice tests with
      both flavours presented in water (552 vs. 409 mL, 571 vs. 414 mL, respectively).
      In the last choice SPC and PDP animals preferred the CS+ over the CS- when both
      flavours were present in feed rather than water (650 vs. 536 g and 678 vs. 513 g,
      respectively). No differences were observed between the conditioning effects of
      the two proteins. In experiment 2, pigs were trained (30 min/day) with a garlic
      flavour (CS) mixed with 4% PDP in sessions 1, 3, 5 and 7 unflavoured tap water in
      sessions 2, 4, 6 and 8 (Conditioned group) or with garlic flavour in water in
      sessions 1, 3, 5 and 7 and 4% PDP without added flavour in sessions 2, 4, 6 and 8
      (control group). In subsequent choice tests conditioned pigs consumed more
      PDP+Garlic than PDP in Tests 1 (550 mL vs. 372 ml, P<0.05) and 3 (763 mL vs. 503
      mL, P<0.05). In addition, pigs in the Conditioned group made significantly more
      first contacts (FC, number of piglets at a pan during the first 15s) with the
      PDP+Garlic solution than PDP solution in Tests 1 and 2 but not in Test 3. In
      contrast, the control group did not differ in their intakes of or first contacts
      to the two PDP solutions. The present results indicate that piglets can acquire
      preferences for a cue flavour added to protein products (PDP and SCP). The
      conditioned flavour preference also enhanced the attraction to the palatable
      protein (PDP) when the flavour and protein were combined.

PMID- 22974752
TI  - Examination of ketamine-induced deficits in sensorimotor gating and spatial
      learning.
AB  - Subanesthetic administration of the NMDA receptor antagonist ketamine has been
      suggested to have utility in several therapeutic domains; however, its
      recreational use has exceeded its therapeutic applications. Ketamine has been
      utilized to investigate NMDA receptor-mediated learning and memory and to model
      disorders such as schizophrenia. The utility of ketamine in relation to
      schizophrenia is based on a proposed mechanism of the disorder being associated
      with reduced NMDA receptor function within a subset of GABAergic neurons. The
      examination of ketamine with relevance to the above topics has produced valuable
      data; however, there exists a great deal of variability in the literature
      regarding dosage and timing of administration to examine ketamine-induced
      deficits. In the below experiments we sought to identify the minimal
      subanesthetic dosage and schedule of ketamine administrations that would produce
      behavioral deficits in multiple tasks with relevance to the above investigations.
      We evaluated sensorimotor gating as well as spatial learning and memory in the
      Morris water task utilizing different doses of ketamine. Our data indicate that
      an 8 mg/kg subcutaneous dose of ketamine was the minimal dose to produce
      impairments in both sensorimotor gating and spatial learning.

PMID- 22974753
TI  - Effect of co-injection of arachydonilcyclopropylamide and ethanol on conditioned
      place preference in rats.
AB  - A combination of cannabis with even a small amount of ethanol can alter the brain
      function, more than either drug alone. To investigate the interacting effects of
      the co-administration of a low dose of ethanol and a cannabinoid CB1 receptor
      agonist, arachidonylcyclopropylamide (ACPA) on the conditioned place preference
      (CPP) test in male Wistar rats, ACPA was injected into the ventral tegmental area
      (VTA), basolateral amygdala (BLA) or ventral hippocampus (VH) in combination with
      ethanol during the conditioning or testing phase. Using a 3-day schedule of
      conditioning, low doses of ethanol (0.25, 0.5 and 1g/kg, i.p.) did not induce CPP
      or conditioned place aversion (CPA). In the second experiment, bilateral intra
      VTA injection of the cannabinoid CB1 receptor agonist,
      arachidonylcyclopropylamide (ACPA; 0.5 and 1 ng/rat) alone or with ethanol (0.5
      g/kg) induced a significant CPA. Bilateral intra-BLA injection of ACPA induced
      significant CPP, while co-administration of the same doses of ACPA with ethanol
      (0.5 g/kg) induced CPA. Bilateral intra-VH injection of ACPA by itself produced
      both CPP and CPA in a dose-dependent manner. Co-administration of an ineffective
      dose of ACPA (9 ng/rat, intra-VH) with ethanol also induced significant CPA. In
      the animals that had received ethanol during the conditioning phase, intra-VTA or
      -VH injection of ACPA, 5 min before the testing phase, produced CPP while intra
      BLA injection of the agonist produced CPA. None of the treatments, except intra
      VH injection of ACPA, had an effect on locomotor activity. In conclusion, there
      may be a functional interaction between endocannabinoid system and ethanol in
      mediating reward or aversion.

PMID- 22974754
TI  - An observational evaluation of move-to-improve, a classroom-based physical
      activity program, New York City schools, 2010.
AB  - INTRODUCTION: Few children in the United States achieve the recommended 60
      minutes of physical activity per day. Identifying successful interventions that
      increase physical activity for children is critical. This observational study
      evaluated the effects of Move-To-Improve (MTI), a classroom-based physical
      education program designed for kindergarten to third-grade teachers in New York
      City public schools. MTI organizes 3-hour trainings for teachers that demonstrate
      strategies for integrating activity into daily classroom schedules. METHODS:
      Randomly sampled elementary schools (N = 39) with classrooms trained in MTI in
      spring 2010 participated in the evaluation. In each school, we observed 2
      classrooms trained in MTI and 2 untrained classrooms in the same school matched
      by grade level for 1 full school day. We analyzed data from 72 trained and 72
      untrained classrooms. RESULTS: Ninety-nine percent of MTI-trained classroom
      teachers led their students in physical activity. MTI-trained classrooms spent an
      average of 9.5 minutes in physical activity per day, compared with 2.4 minutes in
      untrained classrooms (P < .001), an almost fourfold increase in activity. Levels
      of activity were higher in trained versus untrained classrooms regardless of
      grade level or class size. CONCLUSION: Teachers trained in MTI led their
      classrooms in significantly more physical activity compared with teachers who
      were not trained. The MTI program is an effective strategy for increasing
      physical activity during the school day. A curriculum that empowers classroom
      teachers to incorporate activity into their regular day is a practical approach
      to promoting healthier living for children.

PMID- 22974755
TI  - A standardized reporting system for assessment of diverse public health programs.
AB  - State public health agencies face challenges when monitoring the efforts and
      effects of public health programs that use disparate strategies and address
      various diseases, locations, and populations. The external evaluators of a
      complex portfolio of grant funding sought a standardized reporting framework and
      tool that could be used for all grants in the portfolio, without having to
      redesign it for each disease or intervention approach. Evaluators iteratively
      reviewed grant-funded projects to identify common project delivery strategies,
      then developed and implemented a common reporting framework and spreadsheet-based
      data capture tool. Evaluators provided training, technical assistance, and
      ongoing data reviews. During 2 fiscal years, 103 public health programs
      throughout Colorado submitted quarterly reports; agencies funded to implement
      these programs ranged from small community-based organizations to university- and
      hospital-affiliated groups in urban and rural settings. Aggregated reports
      supported estimates of program reach by strategy and by disease area, and the
      system supported production of summary descriptions of program implementation.
      Standardized language and expectations for reporting helped to align grant
      applications and work plans with reporting tools. A common language and
      standardized reporting tool can be used for diverse projects in a comprehensive
      evaluation framework. Decentralized data collection using common spreadsheet
      software enabled the aggregation of common data elements across multiple programs
      and projects. Further refinements could enable wider dissemination of common
      reporting criteria and expectations.

PMID- 22974756
TI  - The cervico-submental keystone island flap for locoregional head and neck
      reconstruction.
AB  - BACKGROUND: Locally advanced head and neck cancer often requires wide resections
      of the cheek and parotid gland, and in an ageing population preferred
      reconstructive options aim to avoid lengthy operating times or high risk surgery.
      While most large parotid defects traditionally require free flap reconstruction,
      we describe a new and versatile locoregional flap that has been shown to be
      reliable, simple and safe. METHODS: We describe the cervico-submental (CSM)
      keystone-design perforator island flap for head and neck reconstruction,
      including an analysis of 33 consecutive patients with a range of head and neck
      defects. The flap was raised based on perforators of the external carotid artery
      and its branches, and designed to overlay the C2/C3 dermatomes (an aide memoire
      for flap design). The indications, and surgical technique are described. RESULTS:
      In 33 consecutive patients, no major complications were encountered. Five
      patients developed superficial infections, one developed post-operative bleeding
      and one patient developed partial tip necrosis. Theatre time was considerably
      shorter than our alternative reconstructive options. CONCLUSION: The CSM keystone
      design perforator island flap is a novel and versatile flap, which can be used in
      a range of advanced cheek and parotidectomy defects, and may enable improved
      surgical management in an increasingly elderly and high-risk population.

PMID- 22974757
TI  - Reconstruction of the external auditory canal using a super-thin superficial
      circumflex iliac perforator flap after tumour resection.
AB  - Reconstruction of the external auditory canal (EAC) after resection of carcinoma
      has become widely performed in combination with tympanoplasty to retain hearing
      ability, thus improving quality of life. Although skin grafting has been commonly
      performed, stenosis, infection and delayed wound healing often occur
      postoperatively. Local flaps can cause less stenosis, but the size and mobility
      are limited. For preventing stenosis and osteoradionecrosis after postoperative
      radiation, super-thin as well as durable resurfacing is required. We present two
      cases of reconstruction of the EAC using a super-thin free superficial circumflex
      iliac perforator (SCIP) flap. The flap was elevated as a super-thin flap
      primarily and inset into the defect as a tube. The flap survived completely
      without stenosis, infection or osteoradionecrosis even after postoperative
      radiation therapy. As this flap can securely cover the important structures,
      causes less stenosis and can endure postoperative radiation therapy, we believe
      that this method could be an option for reconstruction after resection of EAC
      cancers.

PMID- 22974758
TI  - Male goat vocalizations stimulate the estrous behavior and LH secretion in
      anestrous goats that have been previously exposed to bucks.
AB  - We investigated whether live vocalizations emitted by bucks interacting with
      anestrous females stimulate secretion of LH, estrous behavior and ovulation in
      anestrous goats. In experiment 1, bucks rendered sexually active by exposure to
      long days followed by natural photoperiod were exposed in a light-proof-building
      to five anestrous females. Buck vocalizations were reproduced through a
      microphone-amplifier-loudspeaker system to an open pen where one group of goats
      (n=6) was exposed for 10 days to these live vocalizations. Another group of
      females (n=6) was isolated from males and vocalizations. The proportion of goats
      displaying estrous behavior was significantly higher in females exposed to buck
      vocalizations than in females isolated from males. The proportion of goats that
      ovulated did not differ between the 2 groups (exposed to males versus isolated).
      In experiment 2, female goats that either had previous contact with males (n=7),
      or no previous contact with males (n=7) were exposed to live buck vocalizations,
      reproduced as described in experiment 1, for 5 days. The number and amplitude of
      LH pulses did not differ between groups before exposition to buck vocalizations.
      Five days of exposure to male vocalizations significantly increased LH
      pulsatility only in females that had previous contact with males, while LH pulse
      amplitude was not modified. We concluded that live buck vocalizations can
      stimulate estrous behavior and LH secretion in goats if they have had previous
      contact with bucks.

PMID- 22974759
TI  - A critical role of N-myc and STAT interactor (Nmi) in foot-and-mouth disease
      virus (FMDV) 2C-induced apoptosis.
AB  - Foot-and-mouth disease virus (FMDV) 2C, is one of the most highly-conserved viral
      proteins among the serotypes of FMDV. However, its effect on host cells is not
      very clear. Using yeast two-hybrid system and immunoprecipitation approaches, we
      found that FMDV 2C interacted with the N-myc and STAT interactor (Nmi) protein.
      When expressed in cells, FMDV 2C is mainly associated with endoplasmic reticulum
      in the forms of speckles. In the absence of FMDV 2C, Nmi was distributed
      diffusely in the cytoplasm. However, upon FMDV 2C overexpression Nmi was
      recruited into FMDV 2C containing speckles where both proteins are co-localized.
      In addition, FMDV 2C induced apoptosis in BHK-21 cells, which was markedly
      inhibited by Nmi knockdown, suggesting that Nmi may play a critical role in FMDV
      2C-induced apoptosis. These findings may help to further understand the molecular
      mechanism of pathogenesis of FMDV infection.

PMID- 22974761
TI  - EEL spectroscopic tomography: towards a new dimension in nanomaterials analysis.
AB  - Electron tomography is a widely spread technique for recovering the three
      dimensional (3D) shape of nanostructured materials. Using a spectroscopic signal
      to achieve a reconstruction adds a fourth chemical dimension to the 3D structure.
      Up to date, energy filtering of the images in the transmission electron
      microscope (EFTEM) is the usual spectroscopic method even if most of the
      information in the spectrum is lost. Unlike EFTEM tomography, the use of electron
      energy-loss spectroscopy (EELS) spectrum images (SI) for tomographic
      reconstruction retains all chemical information, and the possibilities of this
      new approach still remain to be fully exploited. In this article we prove the
      feasibility of EEL spectroscopic tomography at low voltages (80 kV) and short
      acquisition times from data acquired using an aberration corrected instrument and
      data treatment by Multivariate Analysis (MVA), applied to Fe(x)Co((3
      x))O(4)@Co(3)O(4) mesoporous materials. This approach provides a new scope into
      materials; the recovery of full EELS signal in 3D.

PMID- 22974760
TI  - Aspirin triggered-lipoxin A4 reduces the adhesion of human polymorphonuclear
      neutrophils to endothelial cells initiated by preeclamptic plasma.
AB  - INTRODUCTION: Preeclampsia is a disorder of pregnancy, characterized by
      hypertension and proteinuria after 20 weeks of gestation. Here, we evaluated the
      role of aspirin triggered-lipoxin A(4) (ATL, 15-epi-LXA(4)) on the modulation of
      the adhesion of human polymorphonuclear neutrophils (PMN) to endothelial cells
      initiated by preeclamptic plasma. MATERIALS AND METHODS: Plasma from
      preeclamptic, normotensive pregnant, and non-pregnant women were analyzed for
      factors involved in regulating angiogenesis, inflammation and lipid peroxidation.
      Plasma from preeclamptic women was added to human umbilical vein endothelial
      cells, and the adhesion of PMN (incubated with or without ATL) to cells was
      evaluated. RESULTS: Preeclampsia was associated with some augmented anti
      angiogenic, oxidative and pro-inflammatory markers, as well as increasing human
      PMN-endothelial cell adhesion. This cell adhesion was reduced when human PMN were
      incubated with ATL prior to addition to endothelial monolayers. DISCUSSIONS AND
      CONCLUSIONS: Our results are the starting point for further research on the
      efficacy and rational use of aspirin in preeclampsia.

PMID- 22974762
TI  - Iron chelation inhibits the development of pulmonary vascular remodeling.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of
      pulmonary hypertension. Because iron is an important regulator of ROS biology,
      this study examined the effects of iron chelation on the development of pulmonary
      vascular remodeling. The administration of an iron chelator, deferoxamine, to
      rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary
      vascular remodeling. Various iron chelators inhibited the growth of cultured
      pulmonary artery smooth muscle cells. Protein carbonylation, an important iron
      dependent biological event, was promoted in association with pulmonary vascular
      remodeling and cell growth. A proteomic approach identified that Rho GDP
      dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human
      plasma, the protein carbonyl content was significantly higher in patients with
      idiopathic pulmonary arterial hypertension than in healthy controls. These
      results suggest that iron plays an important role in the ROS-dependent mechanism
      underlying the development of pulmonary hypertension.

PMID- 22974763
TI  - The nitroxide TEMPO is an efficient scavenger of protein radicals: cellular and
      kinetic studies.
AB  - Protein oxidation occurs during multiple human pathologies, and protein radicals
      are known to induce damage to other cell components. Such damage may be modulated
      by agents that scavenge protein radicals. In this study, the potential protective
      reactions of the nitroxide TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl radical)
      against Tyr- and Trp-derived radicals (TyrO./TrpN.) have been investigated.
      Pretreatment of macrophage cells with TEMPO provided protection against photo
      oxidation-induced loss of cell viability and Tyr oxidation, with the nitroxide
      more effective than the hydroxylamine or parent amine. Pulse radiolysis was
      employed to determine rate constants, k, for the reaction of TEMPO with TyrO. and
      TrpN. generated on N-Ac-Tyr-amide and N-Ac-Trp-amide, with values of k~10(8) and
      7*10(6)M(-1)s(-1), respectively, determined. Analogous studies with lysozyme,
      chymotrypsin, and pepsin yielded k for TEMPO reacting with TrpN. ranging from
      1.5*10(7) (lysozyme) to 1.1*10(8) (pepsin)M(-1)s(-1). Pepsin-derived TyrO.
      reacted with TEMPO with k~4*10(7)M(-1)s(-1); analogous reactions for lysozyme and
      chymotrypsin TyrO. were much slower. These data indicate that TEMPO can inhibit
      secondary reactions of both TyrO. and TrpN., though this is protein dependent.
      Such protein radical scavenging may contribute to the positive biological effects
      of nitroxides.

PMID- 22974765
TI  - Sleep apnea-hypopnea syndrome and multiple symmetrical lipomatosis.

PMID- 22974766
TI  - Cost-effectiveness analysis of transbronchial needle aspiration of pulmonary
      lesions without endobronchial affectation.
AB  - Transbronchial needle aspiration (TBNA) of pulmonary lesions without
      endobronchial affectation in combination with transbronchial biopsy (TBB) has
      been shown to increase diagnostic performance. The objective of this present
      study was to analyze whether the combination of TBNA with conventional TBB is a
      cost-effective approach. METHODOLOGY: Ours is a prospective study that included
      patients with lung nodules or masses with no evidence of endobronchial lesions
      after flexible bronchoscopy in whom both TBNA and TBB were performed. We analyzed
      the additional diagnostic value, the impact of TBNA on the cost of the diagnosis
      and the minimum level of sensitivity required in order for TBNA combined with TBB
      to be considered a cost-effective diagnostic approach. RESULTS: Thirty-six
      patients were included in the study, 25 of whom were males. TBB reached a
      histologic diagnosis in 39% of the cases, and its combination with TBNA diagnosed
      47%. The mean diameter of the lesions was significantly greater in the positive
      TBNA cases compared with the negative cases (31 vs. 23mm; p=0,034). The cost
      analysis did not show the additional TBNA to be more cost-effective, despite
      demonstrating greater diagnostic sensitivity. The minimum sensitivity required
      for TBNA combined with TBB to be considered a cost-effective approach was 88%.
      CONCLUSION: The contribution of TBNA to TBB in the diagnosis of lung nodules or
      masses without associated endobronchial lesions does not seem to justify the
      additional economic cost.

PMID- 22974764
TI  - Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and
      lipogenesis.
AB  - We previously observed a stronger effect of knockout of Cu,Zn-superoxide
      dismutase (SOD1) than that of Se-dependent glutathione peroxidase 1 (GPX1) on
      murine body weight and glucose homeostasis. Two experiments were conducted to
      determine how hepatic lipid profiles and key metabolic regulators were correlated
      with this difference. SOD1(-/-) and GPX1(-/-) mice and their respective wild-type
      (WT) littermates (n=6 or 7/group, male) were fed a Se-adequate Torula yeast
      sucrose diet and killed at 6 months of age to collect liver samples. In
      Experiment 1, fasted SOD1(-/-) mice displayed pyruvate intolerance and a 61%
      decrease (P<0.05) in liver glycogen compared with their WT littermates. The
      former had lower (P<0.05) activities of phosphoenolpyruvate carboxykinase, total
      protein phosphatase, and protein phosphatase 2A, but a higher (P<0.05) activity
      of glucokinase in the liver than the latter. In contrast, hepatic concentrations
      of total cholesterol, triglycerides, and nonesterified fatty acids were increased
      by 11 to 100% (P<0.05) in the SOD1(-/-) mice. Meanwhile, these mice had elevated
      (P<0.05) hepatic protein levels of sterol-regulatory element binding proteins 1
      and 2, p53 MAPK, total and phosphorylated AMP-activated protein kinase alpha1
      protein, protein tyrosine phosphatase 1B, and protein phosphatase 2B. In
      Experiment 2, GPX1(-/-) mice and their WT littermates were compared, but showed
      no difference in any of the measures. In conclusion, knockout of SOD1, but not
      GPX1, led to a decreased liver glycogen storage synchronized with pyruvate
      intolerance and elevated hepatic lipid profiles in adult mice. This striking
      comparison was possibly due to unique impacts of these two knockouts on
      intracellular tone of H(2)O(2) and key regulators of liver gluconeogenesis,
      glycolysis, and lipogenesis.

PMID- 22974767
TI  - Wegener's disease and clara cells: eponyms and dignity in respiratory medicine.

PMID- 22974768
TI  - Changes in asthma treatment in the Spanish Cohort of the European Community
      Respiratory Health Survey (ECRHS) from 1991-2001: a perspective over time.

PMID- 22974769
TI  - Anthracostenosis associated with exposure to biomass smoke and presence of
      Mycobacterium tuberculosis.

PMID- 22974770
TI  - Response to a letter to the editor by Dr. Murray M. Finkelstein regarding the
      article by Finley et al. (2012).

PMID- 22974771
TI  - Evaluation of external biosecurity practices on southern Ontario sow farms.
AB  - External biosecurity protocols, aimed at preventing the introduction of new
      pathogens to the farm environment, are becoming increasingly important in the
      swine industry. Although assessments at the individual farm level occur
      regularly, efforts to cluster swine herds into meaningful biosecurity groups and
      to summarize this information at the regional level are relatively infrequent.
      The objectives of this study were: (i) to summarize external biosecurity
      practices on sow farms in southern Ontario; (ii) to cluster these farms into
      discrete biosecurity groups and to describe their characteristics, the variables
      of importance in differentiating between these groups, and their geographic
      distribution; and (iii) to identify significant predictors of biosecurity group
      membership. Data were collected using the Production Animal Disease Risk
      Assessment Program's Survey for the Breeding Herd. A subset of variables
      pertaining to external biosecurity practices was selected for two-step cluster
      analysis, which resulted in 3 discrete biosecurity groups. These groups were
      named by the authors as: (i) high biosecurity herds that were open with respect
      to replacement animals, (ii) high biosecurity herds that were closed with respect
      to replacement animals, and (iii) low biosecurity herds. Variables pertaining to
      trucking practices and the source of replacement animals were the most important
      in differentiating between these groups. Multinomial logistic regression provided
      insight into which demographic and neighborhood variables serve as significant
      predictors of biosecurity group membership (p<0.05). Variables in the final
      regression model include: herd density within a 4.8 km radius, number of sows on
      the premises, and site production type. The odds of belonging to the high
      biosecurity group that was open with respect to replacement animals, relative to
      the low biosecurity group, increased 1.001 times for each additional sow
      (p=0.001). The odds of belonging to the high biosecurity group that was open with
      respect to replacement animals, relative to the low biosecurity group, were 6.5
      times greater for farms that produced genetic animals than for farms that
      produced commercial animals (p=0.003). The information obtained through this work
      allows a better understanding of biosecurity in sow herds at the regional level,
      and the implementation of biosecurity protocols in North American swine herds in
      general.

PMID- 22974772
TI  - Local scanning probe polymerization of an organic monolayer covalently grafted on
      silicon.
AB  - The possibility of lateral extension of conjugation within a covalently grafted
      molecular layer by a scanning probe-based method was tested. A molecular layer
      derived from omega-(N-pyrrolyl)propanol was formed on n-type Si(111) surface.
      Application of large sample biases greater than +/-4 V during conductive atomic
      force microscope (AFM) scans under vacuum resulted in changes of mechanical and
      electrical characteristics of the molecular layer: the tip-sample conductance was
      increased greatly, the friction was reduced significantly, and the surface
      potential of the scanned area was increased. The reduction in friction could be
      attributed to molecular linking formed within the layer. The increased
      conductance suggested extended conjugation among the pyrrolyl end groups.
      Therefore, it was inferred that the biased AFM scan successfully induced local
      polymerization/oligomerization within the covalently grafted molecular layer.

PMID- 22974773
TI  - Is monitoring for mass spawning events in coral assemblages in north Western
      Australia likely to detect spawning?
AB  - In north Western Australia coral reefs occur near ports being developed to
      support rapidly expanding resources industries. Dredging for port construction is
      required to stop during significant mass coral spawning events due to the
      sensitivity of gametes and larvae to increases in turbidity and sedimentation,
      but the timing of this event can vary between seasons and years so monitoring is
      used to predict when spawning is imminent. Here we used simulations to mimick
      sampling strategies currently used in some coral spawning monitoring programmes
      in Western Australia, to assess the ability of these programmes to be able to
      predict multi-specific mass spawning events. We found that current practices may
      sometimes miss spawning events that are likely to be considered large enough to
      warrant stopping dredging. Generally, sampling fewer individuals in a large
      number of species is a better way of monitoring for upcoming spawning than
      sampling a large number of individuals in a small number of species, but overall,
      greater sampling efforts than are currently undertaken are needed if moderately
      sized events are to be detected reliably. Determining exactly how many samples
      are needed, however, depends on having a clearer definition of what actually
      constitutes a "significant mass spawning" event in the first place.

PMID- 22974774
TI  - The scope of the British Journal of Nutrition.

PMID- 22974775
TI  - Lung cancer epidemiology, risk factors, and prevention.
AB  - The greatest risk by far for developing lung cancer is cigarette smoking, but
      age, radon exposure, environmental pollution, occupational exposures, gender,
      race, and pre-existing lung disease also are important contributors. However, not
      all people with these risk factors develop lung cancer, and some without any
      known risk factor do, indicating the importance of genetic influences. Future
      advances in understanding and treating lung cancer will be based on genetic
      analysis. The most effective preventive measure is to never start or to stop
      cigarette smoking.

PMID- 22974776
TI  - Computed tomography screening for lung cancer.
AB  - Screening with low-dose computed tomography reduces mortality from lung cancer in
      high-risk patients. Lung cancer screening with chest radiography alone or in
      combination with sputum analysis is currently not recommended. The feasibility
      and impact of screening in patients with a low or moderate risk for primary lung
      cancer are currently not known. A standardized framework for testing and
      management in a multidisciplinary fashion is necessary to provide lung cancer
      screening. The National Comprehensive Cancer Network and the American Lung
      Association have recently issued guidelines for lung cancer screening with
      computed tomography in high-risk patients.

PMID- 22974777
TI  - Evaluation and management of indeterminate pulmonary nodules.
AB  - The radiologic evaluation and management of the indeterminate solitary pulmonary
      nodule provide common diagnostic dilemma. With continued technologic advancements
      in multidetector computed tomography leading to higher spatial resolution and
      greater overall sensitivity of computed tomography scanners, increasing numbers
      of indeterminate solitary pulmonary nodules are being detected. Malignant and
      benign solitary pulmonary nodules have similar imaging features. Clinical
      management of these incidental nodules relies not only on imaging characteristics
      but also on malignancy risk factors, along with the risks and benefits of further
      investigation.

PMID- 22974778
TI  - The 7th Edition of the TNM staging system for lung cancer: what the radiologist
      needs to know.
AB  - Today lung cancer remains the leading cause of cancer-related death in the United
      States, accounting for 28% of all cases. Radiologists play an important role in
      the assessment of this large number of patients. Given the important role imaging
      plays in the care of patients with lung cancer, it is incumbent on the
      radiologist to have a firm understanding of the TNM (tumor-node-metastasis)
      staging system used to describe the distribution of disease in lung cancer. This
      article reviews the 7th Edition of the TNM staging system for lung cancer and
      important changes from the 6th Edition.

PMID- 22974779
TI  - Optimal imaging protocols for lung cancer staging: CT, PET, MR imaging, and the
      role of imaging.
AB  - Chest radiography, the most commonly performed imaging technique for the
      detection of lung disease, is limited in accurately detecting early lung cancer.
      The main imaging modality for the staging of lung cancer is computed tomography
      (CT), supplemented by positron emission tomography (PET), usually as a hybrid
      technique in conjunction with CT (PET/CT). Magnetic resonance (MR) imaging is a
      useful diagnostic tool for specific indications and has the advantage of not
      using ionizing radiation. This article discusses the optimal imaging protocols
      for lung cancer staging using CT, PET (PET/CT), and MR imaging, and the role of
      imaging in patient management.

PMID- 22974780
TI  - Lung cancer: multidisciplinary approach to tissue sampling.
AB  - Diagnostic confirmation through tissue sampling plays a central role in managing
      patients with suspected lung malignancy. Tissue samples may be obtained in
      various ways using bronchoscopy, computed tomography guidance, or surgery.
      Multidisciplinary discussion between members of the lung cancer care team is
      helpful in assessing the appropriateness of sampling and the best place to sample
      that would establish both the diagnosis and the correct stage of the disease in a
      safe manner.

PMID- 22974781
TI  - Treatment of lung cancer.
AB  - Lung cancer is a heterogenous disease with 2 main subtypes: non-small cell lung
      cancer (NSCLC) and small cell lung cancer (SCLC). Early-stage NSCLC is managed
      primarily by surgical resection, with adjuvant chemotherapy for selected patients
      with stage IB, II, and III disease. Patients with locally advanced stage III
      NSCLC are usually treated with combined modality therapy. Advanced NSCLC remains
      an incurable disease. Further advances will rely on improvements in understanding
      of the molecular events driving the malignant phenotype and the development of
      novel, targeted therapeutic strategies.

PMID- 22974782
TI  - Image-guided ablative therapies for lung cancer.
AB  - Lung cancer is the commonest cause of death in adults. Although the treatment of
      choice is surgical resection with lobectomy, many patients are nonsurgical
      candidates because of medical comorbidities. Patients may also have recurrent
      disease after resection or radiotherapy and some patients refuse surgical
      options. Image-guided ablation has been recently introduced as a safe,
      alternative treatment of localized disease in carefully selected patients. This
      article discusses the principles, technique, and follow-up of the 3 main ablative
      therapies currently used in the lung, radiofrequency ablation, microwave
      ablation, and percutaneous cryotherapy.

PMID- 22974783
TI  - Future trends in lung cancer diagnosis.
AB  - Imaging continues to play an essential role in evaluating patients with lung
      cancer. Improvement in radiologic techniques will produce more accurate
      diagnostic information, but complementing conventional studies with molecular
      diagnostics will likely have an even greater impact on patient management.
      Integration of imaging studies and biomarkers into the diagnostic evaluation of
      patients with lung cancer provides an opportunity to more efficiently guide
      diagnosis, staging, treatment, and follow-up.

PMID- 22974784
TI  - Preface. Lung cancer is an important public health care issue.

PMID- 22974785
TI  - Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid
      arthritis.
AB  - PURPOSE: To evaluate the association between starting early treatment with anti
      TNF and effectiveness as well as the possibility of applying therapeutic spacing
      in daily practice in patients with rheumatoid arthritis (RA). METHODS:
      Observational, retrospective study conducted in two universitary hospitals in
      Spain. RA patients who received the first anti-TNF (adalimumab: ADA, etanercept:
      ETN or infliximab: IFX) during the study period (October 2006-2010) were
      included. Demographic data, time since diagnosis, disease activity (DAS28-ESR)
      and anti-TNF dosage were analyzed. Therapeutic objective was defined as DAS28
      DAS28 < 2.6. Also the response related to criteria of the European League Against
      Rheumatism (EULAR) was evaluated. Therapeutic spacing was defined as the use of a
      lower dose or a higher interval according to label doses. The main endpoint was
      to assess the association between the effectiveness and the moment when the anti
      TNF therapy begins. The secondary target was to evaluate the association between
      RA activity at the beginning of treatment with anti-TNF and dose used. Results.
      82 patients were included. The prescription profile was: ADA (48.8%), ETN (31.7%)
      and IFX (19.5%). 71.4% of patients treated with anti-TNF during the first year
      since diagnosis, 57.1% of those who started after 1-5 years and 30.6% of patients
      who started after 5 years were in remission when the study ended. De-escalation
      strategy was performed in 25.6% of patients: ETN (38.5%), ADA (20.0%) and IFX
      (18.8%). The patients treated with a higher dose according to label doses were:
      IFX (81%), ADA, (12.5%) and ETN (7.7%). CONCLUSIONS: Results suggest that early
      treatment with anti-TNF can achieve a higher percentage of remissions.
      Therapeutic spacing is established as a strategy that improves the efficiency in
      those patients in remission, being the ETN the anti-TNF most susceptible for
      spacing, although a relation between the early beginning with anti-TNF and the
      used dose was not found.

PMID- 22974786
TI  - Effect of inflammation on molecular targets and drug transporters.
AB  - Inflammation, the host's response to infection and injury, is associated with
      altered expression of genes such as metabolizing enzymes, transporters, receptors
      and plasma proteins. The purpose of the present work was to characterize the
      effect of inflammation on selected molecular targets and transporters that affect
      drugs' action and disposition. We have used rats with adjuvant arthritis (AA), an
      animal model of chronic inflammation. The AA group received 0.2 ml of 50 mg ml-1
      Mycobacterium butyricum suspended in squalene into the tail base. On day 12, the
      rats were euthanized and their organs (heart, liver, kidneys and intestine)
      excised. Expression of Cav1.2, beta1-AR, beta2-AR, alpha1A-AR, Nav1.2, Nav1.6,
      Kv1.5, Kv2.1, Kv3.1, oatp1a1, oatp1a5, oatp1b2, oatp2b1, oatp4a1, oat2, oat3,
      oct1, mdr1a, bsep, mrp1, mrp3, mrp6, IL-1alpha, IFN-gamma, iNOS, MCP-1, IL-10,
      Cox-1 and Cox-2 were determined by real time polymerase chain reaction (RT-PCR).
      Inflammation resulted in a significant reduction of oct1, oatp4a1 and mrp1 gene
      expression in the liver and oatp2b1, mrp6 and bsep gene expression in the kidney.
      Oatp4a1 and mdr1a were found to be significantly upregulated in rat heart. In
      conclusion, inflammation alters the gene expression of some mediators and drug
      transporters that can influence the behavior of drugs in the body and contribute
      to therapeutic failure.

PMID- 22974787
TI  - Differential effects of cyclosporin A and tacrolimus on magnesium influx in Caco2
      cells.
AB  - PURPOSE: Hypomagnesemia with urinary magnesium (Mg) wasting is a well
      acknowledged side effect of cyclosporin A (CsA) and tacrolimus (FK506)
      treatments. TRPM6, TRPM7 and MagT1 are involved in the active transcellular Mg
      transport processes in intestine and kidney. Since Mg homeostasis is tightly
      controlled by the dynamic action of intestinal absorption of dietary Mg and renal
      excretion of Mg, we investigated whether CsA and FK506 in commercially available
      solutions for clinical use decrease the expression and the function of TRPM6,
      TRPM7 or MagT1 in the intestinal epithelial cell line Caco2. METHODS: Changes of
      intracellular free Mg concentrations were measured by Mag-fura-2 imaging in Mg
      free medium after the addition of 1 mM MgCl2. TRPM6, TRPM7 and MagT1 were
      evidenced in cells by immunofluorescence. Proteins and mRNAs were quantified
      after 18 hours of treatment with CsA or FK506 by western-blot and real-time RT
      PCR analyses, respectively. RESULTS: TRPM6 and MagT1 were evidenced on all cell
      membranes, TRPM7 only on the inner membranes. CsA was responsible for a profound
      decrease in Mg2+ influx in intestinal epithelial cells, which may result in a
      decrease of intestinal Mg absorption, whereas FK506 was responsible for a marked
      increase in Mg2+ influx. Neither CsA nor FK506 altered TRPM6, TRPM7 or MagT1 mRNA
      levels or MagT1 protein level. CONCLUSIONS: In Caco2 cells, Mg2+ influx was
      inhibited by CsA solutions whereas enhanced by FK506 solutions, without
      alteration of MagT1, TRPM6 and TRPM7 expression, leading to the conclusion that
      CsA and FK506 have opposite effects in the functional activity of the Mg
      transporters herein examined. In clinical use, FK506 should be preferred for
      patients at risk for hypomagnesemia.

PMID- 22974788
TI  - Association of angiotensinogen (M235T) gene polymorphism with blood pressure
      lowering response to angiotensin converting enzyme inhibitor (Enalapril).
AB  - PURPOSE: It has been suggested that genetic backgrounds, which have an
      association with essential hypertension, may also determine the responsiveness to
      ACE inhibitor. We determined the association of angiotensinogen (M235T) gene
      polymorphism with essential hypertension and the relationship between
      polymorphism in the angiotensinogen (M235T) gene and blood pressure response to
      ACE inhibitor (Enalapril) in patients with essential hypertension from northern
      Indian subjects. METHODS: 250 patients with essential hypertension and 250 normal
      healthy controls from Delhi and surrounding areas were recruited for the
      investigation. Blood pressure was recorded before and after 6 weeks of treatment
      with ACE inhibitors, Enalapril. Genotyping were carried out by polymerase chain
      reaction and Restriction fragment length polymorphism technique. RESULTS:
      Statistically significant association of T allele was observed with essential
      hypertension [x2 = 14.67, p = 0.00013, Odds ratio = 1.76 (1.3-2.32) at 95% CI],
      the relative risk at 95% CI being 1.28 (1.2-1.54). The decrease in systolic blood
      pressure and diastolic blood pressure after six weeks of treatment of the
      patients carrying TT genotype (SBP = 26 +/- 17.4 mmHg, DBP = 14.83 +/- 7.6 mmHg)
      were greater than the groups carrying MT (SBP = 3.0 +/- 7.8 mmHg, DBP = 6.2 +/-
      3.0 mmHg) and MM genotypes (SBP = 1.2 +/- 0.8 mmHg, DBP = 0.10 +/- 12.1 mm Hg.
      CONCLUSIONS: The angiotensinogen (M235T) gene polymorphism is significantly
      associated with essential hypertension. Patients carrying TT genotype had higher
      blood pressure lowering response when treated with ACE inhibitor, Enalapril than
      those carrying MM and MT genotypes suggesting that the T allele may be a possible
      genetic marker for essential hypertension.

PMID- 22974789
TI  - Impact of small molecules immunosuppressants on P-glycoprotein activity and T
      cell function.
AB  - PURPOSE: P-glycoprotein (Pgp) is a member of the ABC-transporter family that
      transports substances across cellular membranes acting as an efflux pump
      extruding drugs out of the cells. Pgp plays a key role on the pharmacokinetics of
      several drugs. Herein, we have studied the effects of immunosuppressants on Pgp
      function, assessing rhodamine-123 (Rho123) uptake and efflux in different T-cell
      subsets. METHODS: Different immunosuppressants such as Cyclosporine (CsA),
      Rapamycin (Rapa) and Tacrolimus (Tac) were used to assess the in vitro effect on
      Pgp function of main T-cell subsets among healthy volunteers. We measured Rho123
      uptake, efflux and kinetic of extrusion in CD4+ and CD8+ subsets by flow
      cytometry. Antigen-specific memory T-cell responses were assessed by measuring T
      cell proliferation and cytokine secretion using an allogeneic mixed lymphocyte
      reaction. RESULTS: Rho123 uptake in groups treated with CsA and CsA+Rapa was
      significantly decreased compared to non-treated group and the other
      immunosupressants in both T cells subsets. Pgp activity was also reduced in CsA
      and CsA+Rapa compared to the other immunosupressants but it was only significant
      in the CsA group for CD8+ subset. Kinetic extrusion of Rho123 by Pgp in all
      groups was faster in CD8+ T cells. All immunosuppressants and the specific Pgp
      inhibitor PSC833 diminished antigen-primed T-cell proliferation, especially CD8+
      T-cell subset. CONCLUSIONS: Our data indicate that small molecules
      immunosuppressants, especially CsA, inhibit Pgp activity and T-cell function
      being the CD8+ T cells more susceptible to this effect. These findings support
      the importance of Pgp when designing combined immunosuppressive regimens.

PMID- 22974790
TI  - Fluorescent fatty acid transfer from bovine serum albumin to phospholipid
      vesicles: collision or diffusion mediated uptake.
AB  - PURPOSE: The extent of palmitate uptake by hepatocytes is dependent upon the
      surface charge of the extracellular binding protein. Specifically, hepatocyte
      uptake is greater when palmitate is bound to cationic binding proteins than when
      it is bound to anionic proteins. To further understand the role of protein
      surface charge on the uptake process of protein-bound ligands, we examined the
      rate of transfer of fluorescent anthroyloxy palmitic acid (AOPA) in the presence
      of anionic and cationic extracellular proteins to model membranes containing
      different surface charged groups. METHOD: AOPA transfer rate in the presence of
      bovine serum albumin (ALB; isoelectric point pI = 4.8-5.0) or modified ALB (ALBe;
      pI = 7.0-7.5) to negative, positive and neutral lipid vesicles was investigated
      using a fluorescence resonance energy transfer assay. RESULTS: The rate of AOPA
      transfer from both proteins was decreased when ionic strength was increased;
      directly dependent on the concentration of acceptor lipid vesicles; and was
      affected by both the lipid membrane surface charge and protein-bound
      concentration. CONCLUSION: The data support the notion that AOPA transfer from
      binding proteins to lipid membranes occurred through two concomitant processes,
      aqueous diffusion of the unbound ligand (diffusion-mediated process) and a
      collisional interaction between the protein-ligand complex and acceptor membrane.
      The contribution of diffusional mediated transfer to the overall uptake process
      was determined to be 3 to 4 times less than the contribution of a collisional
      interaction. This study strengthened the hypothesis that charged amino acid
      residues on proteins are important for effective collisional interaction between
      protein-ligand complexes and cell membranes through which more free ligand could
      be supplied for the uptake process.

PMID- 22974792
TI  - Long-term stable cationic solid lipid nanoparticles for the enhanced
      intracellular delivery of SMAD3 antisense oligonucleotides in activated murine
      macrophages.
AB  - PURPOSE: Long-term stable cationic solid lipid nanoparticles (cSLNs) were
      formulated to transfer SMAD3 antisense oligonucleotides (ASOs) into the cells to
      enhance the intracellular activity of the ASOs. The SMAD3 ASOs were designed to
      block the inflammatory processes linked to TGFbeta/SMAD3 pathway. METHODS: The
      cSLN formulation was prepared by high-pressure homogenization method composed of
      1,2-dioleoyl-3-trimethylammonium propane (DOTAP), dioleoylphosphoethanolamine
      (DOPE), Tween 20, and tricaprin as a solid lipid core (1:1:1:1.67, w/w). The size
      and the zeta potential of the prepared cSLNs were measured by light scattering.
      The cSLN/ASO complexes were generated and introduced into the murine macrophage
      cells. After the treatment of the complexes, the cellular uptake of the complexes
      was determined by flow cytometry and the intracellular activity of SMAD3 ASOs
      from the complexes was evaluated by western blotting of SMAD3. In addition,
      TGFbeta1, an upstream molecule of TGFbeta/SMAD3 pathway, was monitored by ELISA.
      RESULTS: The nano-scale sized cSLNs were positively charged and physically stable
      at 4oC during the storage up to 24 months. The uptake efficiency of the cSLN/ASO
      complexes into macrophage cells was enhanced up to 80% without cytotoxicity.
      After the treatment of the cSLN/ASO complexes, SMAD3 as well as TGFbeta1 was
      significantly suppressed based on the SMAD3 ASO activity in the macrophage cells.
      In addition, the cSLN/ASO complexes prevented the morphological change to
      dendritic shape in the activated macrophage cells. CONCLUSION: These results
      suggest that the cSLNs have a potential to deliver the SMAD3 ASOs to
      intracellular compartments for the anti-inflammatory effect. The development of
      this strategy might lead to anti-inflammatory and anti-fibrotic therapies in
      immunological disorders.

PMID- 22974791
TI  - Selection of suitable prodrug candidates for in vivo studies via in vitro
      studies; the correlation of prodrug stability in between cell culture homogenates
      and human tissue homogenates.
AB  - PURPOSE: To determine the correlations/discrepancies of drug stabilities between
      in the homogenates of human culture cells and of human tissues. METHODS: Amino
      acid/dipeptide monoester prodrugs of floxuridine were chosen as the model drugs.
      The stabilities (half-lives) of floxuridine prodrugs in human tissues (pancreas,
      liver, and small intestine) homogenates were obtained and compared with ones in
      cell culture homogenates (AcPC-1, Capan-2, and Caco-2 cells) as well as human
      liver microsomes. The correlations of prodrug stability in human small bowel
      tissue homogenate vs. Caco-2 cell homogenate, human liver tissue homogenate vs.
      human liver microsomes, and human pancreatic tissue homogenate vs. pancreatic
      cell, AsPC-1 and Capan-2, homogenates were examined. RESULTS: The stabilities of
      floxuridine prodrugs in human small bowel homogenate exhibited the great
      correlation to ones in Caco-2 cell homogenate (slope = 1.0-1.3, r2 = 0.79-0.98).
      The stability of those prodrugs in human pancreas tissue homogenate also
      exhibited the good correlations to ones in AsPC-1 and Capan-2 cells homogenates
      (slope = 0.5-0.8, r2 = 0.58-0.79). However, the correlations of prodrug
      stabilities between in human liver tissue homogenates and in human liver
      microsomes were weaker than others (slope = 1.3-1.9, r2 = 0.07-0.24).
      CONCLUSIONS: The correlations of drug stabilities in cultured cell homogenates
      and in human tissue homogenates were compared. Those results exhibited wide range
      of correlations between in cell homogenate and in human tissue homogenate (r2 =
      0.07 - 0.98). Those in vitro studies in cell homogenates would be good tools to
      predict drug stabilities in vivo and to select drug candidates for further
      developments. In the series of experiments, 5'-O-D-valyl-floxuridine and 5'-O-L
      phenylalanyl-L-tyrosyl-floxuridine would be selected as candidates of oral drug
      targeting delivery for cancer chemotherapy due to their relatively good
      stabilities compared to other tested prodrugs.

PMID- 22974793
TI  - Assessment of trophic transfer of benzo(a)pyrene genotoxicity from the post
      larval pink shrimp F. brasiliensis to the juvenile Florida pompano T. carolinus.
AB  - In the present study, the polycyclic aromatic hydrocarbon (PAH) genotoxicity was
      investigated in a one-step predator-prey relationship with the trophic-related
      marine species. Florida pompanos were fed for 5 and 10 days with pink shrimp post
      larvae previously exposed to benzo(a)pyrene (BaP) concentrations. Parent BaP body
      burden was measured in samples of Farfantepenaeus brasiliensis. BaP metabolites
      were determined in bile samples of Trachinotus carolinus and DNA damage was
      assessed through the comet and erythrocyte nuclear abnormalities (ENAs) assays in
      fish erythrocytes. BaP body burden increased significantly with the PAH
      concentration in pink shrimp PLs as well as the fish bile BaP metabolites. Both,
      comet and ENAs assays indicated significant increase on erythrocyte DNA damage of
      Florida pompanos fed with BaP-exposed pink shrimp on both feeding periods. The
      trophic route of BaP genotoxicity is discussed as well as the PAH
      biotransformation as the inducing mechanism for the DNA damages observed.

PMID- 22974794
TI  - Effects of 28 days silicon dioxide aerosol exposure on respiratory parameters,
      blood biochemical variables and lung histopathology in rats.
AB  - Inhalation toxicity of silicon dioxide aerosol (150, 300 mg/m(3)) daily over a
      period of 28 days was carried out in rats. The changes in respiratory variables
      during the period of exposure were monitored using a computer programme that
      recognizes the modifications of the breathing pattern. Exposure to the aerosol
      caused a time dependent decrease in tidal volume, with an increase in respiratory
      frequency compared to the control. Biochemical variables and histopathological
      observation were noted at 28th day following the start of exposure. Biochemical
      markers of silica induced lung injury like plasma alkaline phosphatase, lactate
      dehydrogenase and angiotensine converting enzyme activities increased in a
      concentration dependent manner compared to control. Increase in the plasma
      enzymatic activities indicates endothelial lung damage, increased lung membrane
      permeability. Histopathological observation of the lungs confirmed concentration
      dependent granulomatous inflammation, fibrosis and proteinacious degeneration.
      Aggregates of mononuclear cells with entrapped silica particles circumscribed by
      fibroblast were observed in 300 mg/m(3) silica aerosol exposed group at higher
      magnification. Decrease in tidal volume and increase in respiratory frequency
      might be due to the thickening of the alveolar wall leading to a decreased
      alveolar volume and lowered elasticity of the lung tissue. The trends in
      histological and biochemical data are in conformity with the respiratory data in
      the present study. This study reports for the first time, the changes in
      respiratory variables during silica aerosol exposure over a period of 28 days.

PMID- 22974795
TI  - EROD activity and genotoxicity in the seabob shrimp Xiphopenaeus kroyeri exposed
      to benzo[a]pyrene (BaP) concentrations.
AB  - Seabob shrimp Xiphopenaeus kroyeri is a marine species that lives in shallow
      waters of coastal environments, often impacted by polycyclic aromatic
      hydrocarbons (PAH) pollution. In the present study, seabob shrimp were exposed
      for 96 h to benzo[a]pyrene (BaP) at the nominal concentrations of 100, 200, 400
      and 800 microg-L(-1). Animals of the control groups were exposed either to clean
      water or to the BaP-carrier (DMSO). At the end of the exposures, muscle tissues
      were sampled for BaP uptake assessment and hepatopancreas and hemolymph for EROD
      enzyme activity and hemocytes DNA damage, respectively. EROD activity and DNA
      damage increased significantly as a function of BaP exposure concentrations.
      Significant correlations between BaP uptake and both EROD activity and DNA damage
      suggest that they can be used as suitable tools for integrated levels of study on
      the biomarkers of PAH exposure.

PMID- 22974796
TI  - Loss of adrenergic augmentation of diastolic intra-LV pressure difference in
      patients with diastolic dysfunction: evaluation by color M-mode echocardiography.
AB  - OBJECTIVES: The aim of this study was to evaluate the hypothesis that the
      adrenergic response of the intraventricular pressure difference (IVPD) is reduced
      in patients with preserved ejection fraction (EF) and diastolic dysfunction (DD).
      BACKGROUND: In early diastole, there is a progressive IVPD extending from the
      left atrium (LA) to the left ventricular (LV) apex. In response to adrenergic
      stimulation, as occurs during exercise, the IVPD increases allowing rapid filling
      without an abnormal increase in LA pressure. Patients with heart failure with a
      reduced EF have impaired adrenergic augmentation of the IVPD. METHODS: We studied
      166 consecutive patients undergoing dobutamine stress echocardiography who had no
      inducible ischemia and an EF >=50%, of which 21 had normal diastolic function, 14
      had impaired relaxation (grade 1), 80 had pseudonormal filling (grade 2), and 51
      had restrictive filling (grade 3). Color M-mode Doppler (CMMD) images of mitral
      inflow were obtained at rest and during low (10 MUg/kg/min) and peak (20 to 40
      MUg/kg/min) doses of dobutamine. The total IVPD from the LA to LV apex, LA to mid
      LV, and mid-LV to the LV apex were calculated using the CMMD data to integrate
      the Euler equation. RESULTS: Total IVPD was not different between groups at rest.
      With dobutamine, the total IVPD increased by 2.20 +/- 1.95 mm Hg in normal
      subjects and by only 0.73 +/- 1.33 mm Hg, 1.84 +/- 1.63 mm Hg, and 1.08 +/- 1.57
      mm Hg in patients with grades 1, 2, and 3 DD, respectively. This difference was
      due to a failure in augmentation of IVPD from the mid-LV to the LV apex,
      indicating reduced apical ventricular suction with DD, whereas the IVPD from the
      LA to the mid-LV responded similarly to dobutamine in normal subjects and those
      with DD. CONCLUSIONS: In patients with preserved EF, DD is associated with a
      reduced adrenergic augmentation of the IVPD from the mid-LV to the LV apex,
      reflecting less apical suction.

PMID- 22974797
TI  - HFpEF, diastolic suction, and exercise.

PMID- 22974798
TI  - Coronary calcification and the risk of heart failure in the elderly: the
      Rotterdam Study.
AB  - OBJECTIVES: The purpose of this study was to determine the association of
      coronary artery calcification (CAC) with incident heart failure in the elderly
      and examine its independence of overt coronary heart disease (CHD). BACKGROUND:
      Heart failure is often observed as a first manifestation of coronary
      atherosclerosis rather than a sequela of overt CHD. Although numerous studies
      have shown that CAC, an established measure of coronary atherosclerosis, is a
      strong predictor of CHD, the association between CAC and future heart failure has
      not been studied prospectively. METHODS: In the Rotterdam Study, a population
      based cohort, 1,897 asymptomatic participants (mean age, 69.9 years; 58% women)
      underwent CAC scoring and were followed for the occurrence of heart failure and
      CHD. RESULTS: During a median follow-up of 6.8 years, there were 78 cases of
      heart failure and 76 cases of nonfatal CHD. After adjustment for cardiovascular
      risk factors, increasing CAC scores were associated with heart failure (p for
      trend = 0.001), with a hazard ratio of 4.1 (95% confidence interval [CI]: 1.7 to
      10.1) for CAC scores >400 compared with CAC scores of 0 to 10. After censoring
      participants for incident nonfatal CHD, increasing extent of CAC remained
      associated with heart failure (p for trend = 0.046), with a hazard ratio of 2.9
      (95% CI: 1.1 to 7.4) for CAC scores >400. Moreover, adding CAC to cardiovascular
      risk factors resulted in an optimism-corrected increase in the c-statistic by
      0.030 (95% CI: 0.001 to 0.050) to 0.734 (95% CI: 0.698 to 0.770) and
      substantially improved the risk classification of subjects (continuous net
      reclassification index = 34.0%). CONCLUSIONS: CAC has a clear association with
      the risk of heart failure, independent of overt CHD. Because heart failure is
      highly prevalent in the elderly, it might be worthwhile to include heart failure
      as an outcome in future risk assessment programs incorporating CAC.

PMID- 22974799
TI  - What if we could prevent heart failure?

PMID- 22974800
TI  - Acute left ventricular remodeling following myocardial infarction: coupling of
      regional healing with remote extracellular matrix expansion.
AB  - OBJECTIVES: This prospective study aimed to assess regional and temporal patterns
      of extracellular matrix (ECM) changes post-myocardial infarction (MI).
      BACKGROUND: A fundamental process in the development of ischemic left ventricular
      (LV) dysfunction is LV remodeling, characterized by structural and functional
      abnormalities throughout the myocardium including the noninfarcted (remote)
      myocardium and interstitium. METHODS: Contrast-enhanced cardiac magnetic
      resonance (CMR) was performed on MI patients acutely (mean: 5 days post-MI, n =
      25) and repeated subacutely (mean: 139 days post-MI, n = 21), and was also
      performed in a separate group of 15 patients with chronic MI (mean: 2,580 days
      post-MI, n = 15). Twenty volunteers without a history of MI acted as controls.
      CMR was used to evaluate LV morphology and function, with post-contrast T1
      mapping to semiquantitatively assess changes in the ECM. Putative mediators of
      myocardial inflammation and fibrosis, including macrophage migration inhibitory
      factor (MIF), were also measured. RESULTS: Age, sex, and diabetic and
      hypertensive status did not differ between MI groups and controls. Compared with
      controls, patients early post-acute MI demonstrated reduced LV ejection fraction
      (50.25 +/- 7.29% vs. 66.7 +/- 6.2% [controls], p < 0.0001). Myocardium remote to
      the infarction early post-acute MI, compared with controls, demonstrated reduced
      systolic thickening (60 +/- 5.0% vs. 106 +/- 7.6%, p <= 0.0002), and lower post
      contrast myocardial T1 times suggestive of ECM expansion (437 +/- 113 ms vs. 549
      +/- 119 ms, p = 0.01). In a subgroup analysis between early post-acute MI and
      controls of similar age and sex, the remote sector post-contrast myocardial T1
      times remained significantly shorter post-acute MI compared with controls (420 +/
      121 ms vs. 529 +/- 113 ms, p = 0.03). Serum levels of MIF inversely correlated
      with global myocardial T1 time in patients early post-acute MI (r = -0.6, p =
      0.01), suggesting a coupling of regional healing with acute LV remodeling.
      CONCLUSIONS: Within a week of acute MI, the remote myocardium exhibits systolic
      dysfunction and expansion of the ECM, which is coupled with physiological infarct
      healing. Further prospective studies with larger sample sizes are needed to
      verify these important findings.

PMID- 22974801
TI  - Understanding LV remodeling following myocardial infarction: are T1 maps by CMR
      the new guide?

PMID- 22974803
TI  - Extracellular space measurements with CMR imaging.

PMID- 22974802
TI  - Quantification of extracellular matrix expansion by CMR in infiltrative heart
      disease.
AB  - OBJECTIVES: The aim of this study was to perform direct quantification of
      myocardial extracellular volume fraction (ECF) with T1-weighted cardiac magnetic
      resonance (CMR) imaging in patients suspected to have infiltrative heart disease.
      BACKGROUND: Infiltrative heart disease refers to accumulation of abnormal
      substances within the myocardium. Qualitative assessment of late gadolinium
      enhancement (LGE) remains the most commonly used method for CMR evaluation of
      patients suspected with myocardial infiltration. This technique is widely
      available and can be performed in a reproducible and standardized manner.
      However, the degree of extracellular matrix expansion due to myocardial
      infiltration in the intercellular space has, to date, not been amenable to
      noninvasive quantification with LGE. METHODS: We performed 3-T CMR in 38 patients
      (mean age 68 +/- 15 years) who were referred for assessment of infiltrative heart
      disease and also in 9 healthy volunteers as control subjects. The T1
      quantification by Look-Locker gradient-echo before and after contrast determined
      segmental myocardial partition coefficients. The ECF was obtained by referencing
      the tissue partition coefficient for gadolinium to the plasma volume fraction in
      blood, derived from serum hematocrit. Cine CMR and LGE imaging in matching
      locations were also performed. RESULTS: Seventeen patients (45%) had cardiac
      amyloidosis (CA) (biopsy-confirmed or clinically highly probable), 20 (53%) had a
      non-amyloid cardiomyopathy, and 1 had lysosomal storage disease. Median global
      ECF was substantially higher in CA patients (0.49) compared with non-amyloid
      cardiomyopathy patients (0.33, p < 0.0001) and volunteers (0.24, p = 0.0001). The
      ECF strongly correlated with visually assessed segmental LGE (r = 0.80, p <
      0.0001) and LV mass index (r = 0.69, p < 0.0001), reflecting severity of
      myocardial infiltration. In patients with CA, ECF was highest in segments with
      LGE, although it remained elevated in segments without qualitative LGE.
      CONCLUSIONS: The CMR ECF quantification identified substantial expansion of the
      interstitial space in patients with CA compared with volunteers. Further studies
      using this technique for diagnosis and assessment of the severity of myocardial
      infiltration are warranted.

PMID- 22974804
TI  - Effects of p38 mitogen-activated protein kinase inhibition on vascular and
      systemic inflammation in patients with atherosclerosis.
AB  - OBJECTIVES: This study sought to determine the effects of a p38 mitogen-activated
      protein kinase inhibitor, losmapimod, on vascular inflammation, by (18)F
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      imaging. BACKGROUND: The p38 mitogen-activated protein kinase cascade plays an
      important role in the initiation and progression of inflammatory diseases,
      including atherosclerosis. METHODS: Patients with atherosclerosis on stable
      statin therapy (n = 99) were randomized to receive losmapimod 7.5 mg once daily
      (lower dose [LD]), twice daily (higher dose [HD]) or placebo for 84 days.
      Vascular inflammation was assessed by FDG positron emission tomography/computed
      tomography imaging of the carotid arteries and aorta; analyses focused on the
      index vessel (the artery with the highest average maximum tissue-to-background
      ratio [TBR] at baseline). Serum inflammatory biomarkers and FDG uptake in
      visceral and subcutaneous fat were also measured. RESULTS: The primary endpoint,
      change from baseline in average TBR across all segments in the index vessel, was
      not significantly different between HD and placebo (DeltaTBR: -0.04 [95%
      confidence interval [CI]: -0.14 to +0.06], p = 0.452) or LD and placebo
      (DeltaTBR: -0.02 [95% CI: -0.11 to +0.06], p = 0.579). However, there was a
      statistically significant reduction in average TBR in active segments (TBR >=1.6)
      (HD vs. placebo: DeltaTBR: -0.10 [95% CI: -0.19 to -0.02], p = 0.0125; LD vs.
      placebo: DeltaTBR: -0.10 [95% CI: -0.18 to -0.02], p = 0.0194). The probability
      of a segment being active was also significantly reduced for HD when compared
      with placebo (OR: 0.57 [95% CI: 0.41 to 0.81], p = 0.002). Within the HD group,
      reductions were observed in placebo-corrected inflammatory biomarkers including
      high-sensitivity C-reactive protein (% reduction: -28% [95% CI: -46 to -5], p =
      0.023) as well as FDG uptake in visceral fat (DeltaSUV: -0.05 [95% CI: -0.09 to 
      0.01], p = 0.018), but not subcutaneous fat. CONCLUSIONS: Despite nonsignificant
      changes for the primary endpoint of average vessel TBR, HD losmapimod reduced
      vascular inflammation in the most inflamed regions, concurrent with a reduction
      in inflammatory biomarkers and FDG uptake in visceral fat. These results suggest
      a systemic anti-inflammatory effect. (A Study to Evaluate the Effects of 3 Months
      Dosing With GW856553, as Assessed FDG-PET/CT Imaging; NCT00633022).

PMID- 22974806
TI  - Use of coronary artery calcium scanning to screen for coronary atherosclerosis
      among early middle-age adults.

PMID- 22974805
TI  - Yield of screening for coronary artery calcium in early middle-age adults based
      on the 10-year Framingham Risk Score: the CARDIA study.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence and
      distribution of coronary artery calcium (CAC) across Framingham Risk Score (FRS)
      strata and therefore determine FRS levels at which asymptomatic, young to early
      middle-age individuals could potentially benefit from CAC screening. BACKGROUND:
      High CAC burden is associated with increased risk of coronary events beyond the
      FRS. Expert panel recommendations for CAC screening are based on data obtained in
      middle-age and older individuals. METHODS: We included 2,831 CARDIA (Coronary
      Artery Risk Development in Young Adults) study participants with an age range of
      33 to 45 years. The number needed to screen ([NNS] number of people in each FRS
      stratum who need to be screened to detect 1 person with a CAC score above the
      specified cut point) was used to assess the yield of screening for CAC. CAC
      prevalence was compared across FRS strata using a chi-square test. RESULTS: CAC
      scores >0 and >=100 were present in 9.9% and 1.8% of participants, respectively.
      CAC prevalence and amount increased across higher FRS strata. A CAC score >0 was
      observed in 7.3%, 20.2%, 19.1%, and 44.8% of individuals with FRSs of 0 to 2.5%,
      2.6% to 5%, 5.1% to 10%, and >10%, respectively (NNS = 14, 5, 5, and 2,
      respectively). A CAC score of >=100 was observed in 1.3%, 2.4%, and 3.5% of those
      with FRSs of 0 to 2.5%, 2.6% to 5%, and 5.1% to 10%, respectively (NNS = 79, 41,
      and 29, respectively), but in 17.2% of those with an FRS >10% (NNS = 6). Similar
      trends were observed when findings were stratified by sex and race. CONCLUSIONS:
      In this young to early middle-age cohort, we observed concordance between CAC
      prevalence/amount and FRS strata. Within this group, the yield of screening and
      possibility of identifying those with a high CAC burden (CAC score of >=100) is
      low in those with an FRS of <=10%, but considerable in those with an FRS >10%.

PMID- 22974807
TI  - IVUS detection of vasa vasorum blood flow distribution in coronary artery vessel
      wall.
AB  - There is an increased body of evidence to suggest that the vasa vasorum play a
      major role in the progression and complications of vulnerable plaque leading to
      acute coronary syndrome. We propose that detecting changes in the flow in the
      vascular wall by intravascular ultrasound signals can quantify the presence of
      vasa vasorum. The results obtained in a porcine model of atherosclerosis suggest
      that intravascular ultrasound-based estimates of blood flow in the arterial wall
      can be used in vivo in a clinical research setting to establish the density of
      vasa vasorum as an indicator of plaque vulnerability.

PMID- 22974809
TI  - Imaging of prosthetic heart valve dysfunction: complementary diagnostic value of
      TEE and MDCT?

PMID- 22974810
TI  - Contrast enhancement imaging in coronary arteries in SLE.

PMID- 22974808
TI  - Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group
      on current status and future directions.
AB  - The leading cause of major morbidity and mortality in most countries around the
      world is atherosclerotic cardiovascular disease, most commonly caused by
      thrombotic occlusion of a high-risk coronary plaque resulting in myocardial
      infarction or cardiac death, or embolization from a high-risk carotid plaque
      resulting in stroke. The lesions prone to result in such clinical events are
      termed vulnerable or high-risk plaques, and their identification may lead to the
      development of pharmacological and mechanical intervention strategies to prevent
      such events. Autopsy studies from patients dying of acute myocardial infarction
      or sudden death have shown that such events typically arise from specific types
      of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However,
      the search in human beings for vulnerable plaques before their becoming
      symptomatic has been elusive. Recently, the PROSPECT (Providing Regional
      Observations to Study Predictors of Events in the Coronary Tree) study
      demonstrated that coronary plaques that are likely to cause future cardiac
      events, regardless of angiographic severity, are characterized by large plaque
      burden and small lumen area and/or are thin-cap fibroatheromas verified by
      radiofrequency intravascular ultrasound imaging. This study opened the door to
      identifying additional invasive and noninvasive imaging modalities that may
      improve detection of high-risk atherosclerotic lesions and patients. Beyond
      classic risk factors, novel biomarkers and genetic profiling may identify those
      patients in whom noninvasive imaging for vulnerable plaque screening, followed by
      invasive imaging for risk confirmation is warranted, and in whom future
      pharmacological and/or device-based focal or regional therapies may be applied to
      improve long-term prognosis.

PMID- 22974811
TI  - Will procedural complexity cultivate interdisciplinary camaraderie?

PMID- 22974812
TI  - The association of metatarsus adductus to the proximal fifth metatarsal Jones
      fracture.
AB  - This retrospective study aimed to determine if a transverse plane forefoot
      relationship exists in patients with Jones fractures. Anteroposterior radiographs
      of 30 acute Jones fractures were compared with radiographs of 30 asymptomatic
      control subjects. Radiographic metatarsus adductus angle measurements were
      analyzed with a digital software program. The reliability of the measurements was
      evaluated with an intra-rater study. An independent t test was used to compare
      the metatarsus adductus angle between the Jones fracture group and the control
      group. Radiographic analysis revealed the mean metatarsus adductus angle for the
      Jones fracture group to be 20.22 degrees  (+/- 6.79 degrees ) compared with a
      mean of 14.27 degrees  (+/- 4.60 degrees ) for the control group. This difference
      between the groups was found to be statistically significant (p < .005). The
      intraclass reliability coefficient (ICC = 0.9396) confirmed there was no bias in
      the radiographic measurements. The metatarsus adductus angle in this group of
      patients with Jones fractures was increased compared with the nonpathologic
      control group. The Jones fracture mechanism of injury and resultant lateral
      column overload may be intensified with an increased metatarsus adductus. This
      relationship should be considered a risk factor for Jones fractures and taken
      into consideration with respect to bone healing, treatment, and prevention.

PMID- 22974813
TI  - Is percutaneous radiofrequency coblation for treatment of Achilles tendinosis
      safe and effective?
AB  - Insertional Achilles tendinosis results in isolated pain at the Achilles tendon
      insertion site due to intratendinous degeneration. When conservative measures
      fail, surgical treatment may be necessary. Radiofrequency coblation has been
      suggested to be an effective procedure for treatment of tendon pathologies.
      Percutaneous execution of this procedure is very simple as well as minimally
      invasive, and thus if effective, would be an excellent alternative to an open
      treatment of insertional Achilles tendinopathy. A review of 47 cases with this
      percutaneous technique was conducted. In our relatively short-term follow-up
      (mean = 8.6 months, SD = 9.71, range 1 to 40), the incidence of reoperation was
      14.9% (7/47). Rupture of the Achilles tendon was identified in 3 (6.4%) patients.
      Our cohort had a relatively high body mass index (mean = 37.1, SD = 6.96, range
      24.3 to 52.8). We recommend surgeons to be cautious about selecting this
      procedure in similar, high body mass index patient cohorts for treatment of
      Achilles tendinosis.

PMID- 22974814
TI  - Distraction arthrodesis of subtalar joint using a laterally placed hinged
      distractor.
AB  - Many joint-depressive, neglected calcaneal fractures need distraction arthrodesis
      of the subtalar joint. Because the calcaneal tuberosity is usually malunited in
      the varus position, more distraction is required on the medial side to place the
      tuberosity in the everted position before insertion of a bone graft.
      Traditionally, a distractor is placed on the medial side to achieve this task.
      However, the medially placed distractor hinders with the positioning of the
      extremity and exposure of the main operative site, which is commonly on the
      lateral side. We introduce a technique to avoid this burden by placing a hinged
      distractor device on the lateral aspect of the foot while maintaining the
      correction of the varus deformity.

PMID- 22974815
TI  - The effect of d-amino acid substitution on the selectivity of temporin L towards
      target cells: identification of a potent anti-Candida peptide.
AB  - The frog skin peptide temporin L (TL, 13-residues long) has a wide and potent
      spectrum of antimicrobial activity, but it is also toxic on mammalian cells at
      its microbicidal concentrations. Previous studies have indicated that its
      analogue [Pro(3)]TL has a slightly reduced hemolytic activity and a stable
      helical conformation along residues 6-13. Here, to expand our knowledge on the
      relationship between the extent/position of alpha-helix in TL and its biological
      activities, we systematically replaced single amino acids within the alpha
      helical domain of [Pro(3)]TL with the corresponding d isomers, known as helix
      breakers. Structure-activity relationship studies of these analogues, by means of
      CD and NMR spectroscopy analyses as well as antimicrobial and hemolytic assays
      were performed. Besides increasing our understanding on the structural elements
      that are responsible for cell selectivity of TL, this study revealed that a
      single l to d amino acid substitution can preserve strong anti-Candida activity
      of [Pro(3)]TL, without giving a toxic effect towards human cells.

PMID- 22974816
TI  - Characterization of the diffusion of epidermal growth factor receptor clusters by
      single particle tracking.
AB  - A number of studies have shown that receptors of the epidermal growth factor
      receptor family (ErbBs) exist as higher-order oligomers (clusters) in cell
      membranes in addition to their monomeric and dimeric forms. Characterizing the
      lateral diffusion of such clusters may provide insights into their dynamics and
      help elucidate their functional relevance. To that end, we used single particle
      tracking to study the diffusion of clusters of the epidermal growth factor (EGF)
      receptor (EGFR; ErbB1) containing bound fluorescently-labeled ligand, EGF. EGFR
      clusters had a median diffusivity of 6.8*10(-11)cm(2)/s and were found to exhibit
      different modes of transport (immobile, simple, confined, and directed) similar
      to that previously reported for single EGFR molecules. Disruption of actin
      filaments increased the median diffusivity of EGFR clusters to 10.3*10(
      11)cm(2)/s, while preserving the different modes of diffusion. Interestingly,
      disruption of microtubules rendered EGFR clusters nearly immobile. Our data
      suggests that microtubules may play an important role in the diffusion of EGFR
      clusters either directly or perhaps indirectly via other mechanisms. To our
      knowledge, this is the first report probing the effect of the cytoskeleton on the
      diffusion of EGFR clusters in the membranes of live cells.

PMID- 22974817
TI  - New insights into lipid-Nucleoside Diphosphate Kinase-D interaction mechanism:
      protein structural changes and membrane reorganisation.
AB  - Nucleoside Diphosphate Kinases (NDPKs) have long been considered merely as
      housekeeping enzymes. The discovery of the NME1 gene, an anti-metastatic gene
      coding for NDPK-A, led the scientific community to re-evaluate their role in the
      cell. It is now well established that the NDPK family is more complex than what
      was first thought, and despite the increasing amount of evidence suggesting the
      multifunctional role of nm23/NDPKs, the specific functions of each family member
      are still elusive. Among these isoforms, NDPK-D is the only one to present a
      mitochondria-targeting sequence. It has recently been shown that this protein is
      able to bind and cross-link with mitochondrial membranes, suggesting that NDPK-D
      can mediate contact sites and contributes to the mitochondrial intermembrane
      space structuring. To better understand the influence of NDPK-D on mitochondrial
      lipid organisation, we analysed its behaviour in different lipid environments. We
      found that NDPK-D not only interacts with CL or anionic lipids, but is also able
      to bind in a non negligible manner to zwitterionic PC. NDPK-D alters membrane
      organisation in terms of fluidity, hydration and lipid clustering, effects which
      depend on lipid structure. Changes in the protein structure after lipid binding
      were evidenced, both by fluorescence and infrared spectroscopy, regardless of
      membrane composition. Taking into account all these elements, a putative
      mechanism of interaction between NDPK-D and zwitterionic or anionic lipids was
      proposed.

PMID- 22974818
TI  - Aqueous humor oxidative stress proteomic levels in primary open angle glaucoma.
AB  - The purpose of this work was to investigate the expression of glutamine synthase
      (GS), nitric oxide synthase (NOS) superoxide dismutase (SOD) and glutathione
      transferase (GST) in the aqueous humor of patients with primary open angle
      glaucoma and controls. Aqueous humor proteome was analyzed by antibody
      microarray. The expression of tested proteins was detected by protein Cy3/Cy5
      labeling, column purification and hybridization on antibody-spotted glass
      microarray. Fluorescent signals were detected by fluorescence laser scanning.
      Aqueous humor levels of SOD as well as of GST were significantly lower (2.0- and
      2.2-fold, p < 0.01) among patients than controls; both NOS and GS expression were
      significantly higher (2.2- and 2.6 fold, p < 0.01) among patients than controls.
      Our data showed substantial differences of GS, NOS2, SOD and GST aqueous humor
      levels between glaucomatous patients and controls as measured by antibody
      microarray technology. The overproduction of NO through inducible NOS can form
      toxic products and change the metabolic conditions of the TM. The GS over
      expression might be related to neuronal injury or to the potential role of
      glutamate as a modulator in the ciliary body signaling. The reduced expression of
      the antioxidant enzymes SOD and GST could aggravate the unbalance between both
      oxygen- and nitrogen-derived free radicals production and detoxification. Based
      on our results, GS, NOS2, SOD and GST as measured by antibody microarray
      technology may be useful oxidative markers in aqueous humor of glaucomatous
      patients.

PMID- 22974819
TI  - The role and contribution of the third sector in terms of waste management and
      resource recovery.

PMID- 22974822
TI  - Cytokine mucosal expression in ulcerative colitis, the relationship between
      cytokine release and disease activity.
AB  - BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with
      conflicting evidence from studies on the roles of TNFalpha, IL-8, TGFbeta and
      other cytokines and characterised by neutrophil infiltration and tissue
      destruction. AIM: To compare cytokine profiles of inflamed and non-inflamed
      mucosa in patients with distal UC, and matched controls. METHODS: Patients were
      prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were
      taken from UC patients within macroscopically inflamed and non-inflamed proximal
      mucosa, and from age-sex matched controls undergoing FS. Endoscopic and
      histological inflammation was graded. Quantitative cytokine analysis for IL-4,
      TNFalpha, IL-17A, IL-8, IL-10, TGFbeta and IFNgamma was carried out on tissue
      homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis,
      Mann-Whitney U test and Spearman's correlation. RESULTS: 69 active UC patients
      (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In
      inflamed mucosa, elevation in IL-8 and reduction in TGFbeta was measured compared
      with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001);
      IL-8 was positively correlated (rs=0.481, p<0.01) and TGFbeta inversely
      correlated (rs=0.462; p<0.01) with grade of inflammation. TNFalpha concentration
      was not significantly different. Comparisons of inflamed with non-inflamed mucosa
      also demonstrate significant reduction in concentration of IFNgamma (p<0.001), IL
      4 (p<0.005) and IL-17A (p<0.002). CONCLUSION: Our findings suggest that IL-8 is
      elevated and TGFbeta is reduced in distal colitis. Lower concentration of
      IFNgamma, IL-4 and IL-17A were also noted. TNFalpha levels were unchanged. These
      findings suggest that the inflammatory response in UC may predominantly involve
      IL-8 mediated neutrophil infiltration and failure of TGFbeta mediated tissue
      healing.

PMID- 22974824
TI  - The human milk microbiota: origin and potential roles in health and disease.
AB  - Human milk has been traditionally considered sterile; however, recent studies
      have shown that it represents a continuous supply of commensal, mutualistic
      and/or potentially probiotic bacteria to the infant gut. Culture-dependent and 
      independent techniques have revealed the dominance of staphylococci,
      streptococci, lactic acid bacteria and bifidobacteria in this biological fluid,
      and their role on the colonization of the infant gut. These bacteria could
      protect the infant against infections and contribute to the maturation of the
      immune system, among other functions. Different studies suggest that some
      bacteria present in the maternal gut could reach the mammary gland during late
      pregnancy and lactation through a mechanism involving gut monocytes. Thus,
      modulation of maternal gut microbiota during pregnancy and lactation could have a
      direct effect on infant health. On the other hand, mammary dysbiosis may lead to
      mastitis, a condition that represents the first medical cause for undesired
      weaning. Selected strains isolated from breast milk can be good candidates for
      use as probiotics. In this review, their potential uses for the treatment of
      mastitis and to inhibit mother-to-infant transfer of HIV are discussed.

PMID- 22974823
TI  - Reverse-mode Na+/Ca2+ exchange is an important mediator of venous contraction.
AB  - The Na(+)/Ca(2+) exchanger (NCX) is a bi-directional regulator of cytosolic
      Ca(2+), causing Ca(2+) efflux in forward-mode and Ca(2+) influx in reverse-mode.
      We hypothesized that reverse-mode NCX is a means of Ca(2+) entry in rat aorta
      (RA) and vena cava (RVC). NCX protein in RA and RVC was confirmed by
      immunoprecipitation. To assess NCX function, isometric contraction and
      intracellular Ca(2+) was measured in RA and RVC rings in response to low
      extracellular Na(+), endothelin-1 (ET-1), and KCl, in the presence or absence of
      the NCX antagonist KB-R7943. In RVC, low extracellular Na(+) caused
      vasoconstriction and an increase in intracellular Ca(2+) that was attenuated by
      10MUM KB-R7943. KB-R7943 (10 MUM) attenuated maximal contraction to ET-1 in RVC
      (53 +/- 9% of control), but not RA (91+/-1% of control). KB-R7943 (10 MUM)
      reduced the maximal contraction to KCl in RA (48 +/- 5%) and nearly abolished it
      in RVC (9 +/- 2%), suggesting that voltage-dependent Ca(2+) influx may be
      inhibited by KB-R7943 as well. However, the L-type Ca(2+) channel inhibitor
      nifedipine (1 MUM) did not alter ET-1-induced contraction. Our findings suggest
      that reverse-mode NCX is an important mechanism of Ca(2+) influx in RVC but not
      RA, especially during ET-1-induced contraction. Also, the effects of KB-R7943 on
      ET-1-induced contraction of RA and RVC are predominantly mediated by reverse-mode
      NCX inhibition and not due to off-target inhibition of Ca(2+) channels.

PMID- 22974825
TI  - Biotransformation of progesterone by Absidia griseolla var. igachii and
      Rhizomucor pusillus.
AB  - Biotransformation of progesterone using Absidia griseolla var. igachii and
      Rhizomucor pusillus strains as biocatalysts were investigated. Microbial
      hydroxylation of progesterone by A. griseolla produced two hydroxylated pregnane
      like steroids. The metabolites identified as 6beta,14alpha-dihydroxyprogesterone
      and 7alpha,14alpha-dihydroxyprogesterone. R. pusillus produced 6beta,11alpha
      dihydroxyprogesterone with excellent yield (65.5%) and 7alpha,14alpha
      dihydroxyprogesterone. These metabolites were purified by TLC followed by their
      identification through (1)H, (13)C NMR and other spectroscopic data.

PMID- 22974826
TI  - Brassinosteroids inhibit in vitro angiogenesis in human endothelial cells.
AB  - Antiangiogenic activity of the brassinosteroid plant hormones (BRs) and their
      derivative cholestanon was investigated in human umbilical vein endothelial cells
      (HUVEC) and in human microvascular endothelial cells (HMEC-1). 24-Epibrassinolide
      and 28-homocastasterone from group of 21 tested natural BRs inhibited migration
      of HUVEC cells. Seven tested BRs decreased the number of tubes significantly.
      Synthetic analogue cholestanon inhibited angiogenesis in vitro more effectively
      than natural BRs. Because of the similarity of BRs to human steroids, we have
      also studied interactions of BRs with human steroid receptors. Synthetic BRs
      cholestanon showed agonistic effects on estrogen-receptor-alpha, estrogen
      receptor-beta and androgen receptor. Of the natural BRs, 24-epibrassinolide was
      found to be a weak antagonist of estrogen-receptor-alpha (ERalpha). Our results
      provide the first evidence that large group of BRs can inhibit in vitro
      angiogenesis of primary endothelial cells. BRs constitute a novel group of human
      steroid receptor activators or inhibitors with capacity to inhibit angiogenesis.

PMID- 22974827
TI  - A novel chenodeoxycholic acid-verticinone ester induces apoptosis and cell cycle
      arrest in HepG2 cells.
AB  - In this study, the in vitro antitumor activity of chenodeoxycholic acid
      verticinone ester (CDCA-Ver), a novel compound and its underlying mechanisms were
      evaluated. Results showed that CDCA-Ver significantly inhibited HepG2 cell
      viability in a both dose- and time-dependent manner, moreover CDCA-Ver induced
      apoptotic cell death and G(0)/G(1) cell cycle arrest in HepG2 cells. ROS
      generation, loss of balance of Bax/Bcl-2 ratio, loss of mitochondrial
      transmembrane potential, activation of caspases and elevation of intracellular
      free Ca(2+) concentration were involved in the CDCA-Ver induced apoptosis pathway
      in HepG2 cells. We concluded that CDCA-Ver may be a potential candidate for the
      therapy of cancer.

PMID- 22974828
TI  - Steroids excreted in urine by neonates with 21-hydroxylase deficiency. 3.
      Characterization, using GC-MS and GC-MS/MS, of androstanes and androstenes.
AB  - Urine from neonates with 21-hydroxylase deficiency contains a large range of
      androstane(ene)s, many of which have not been previously described. We present
      their characterization as the third part of a comprehensive study of urinary
      steroids, aiming to enhance the diagnosis of this disorder and to further
      elucidate steroid metabolism in neonates. Steroids were analyzed, after
      extraction and enzymatic conjugate hydrolysis, as methyloxime-trimethylsilyl
      ether derivatives on gas-chromatographs coupled to quadrupole and ion-trap mass
      spectrometers. GC-MS and GC-MS/MS spectra were used together to determine the
      structure of hitherto undescribed androstane(ene)s. GC-MS/MS was pivotal for the
      structural characterization of 2-hydroxylated androstenediones but GC-MS was
      generally more informative for androstane(ene)s, in contrast to 17-hydroxylated
      pregnane(ene)s. Parallels were found between the GC-MS and GC-MS/MS
      characteristics of structurally similar androstenediones and progesterones
      without a substituent on the D-ring, but not with those of 17-hydroxylated
      progesterones. Assignment of 5alpha(beta) orientation, based on GC-MS
      characteristics, was possible for 11-oxo-androstanes. The major endogenous 3beta
      hydroxy-5-enes in 21-hydroxylase deficiency did not differ from those in
      unaffected neonates. The key qualitative and quantitative differences encompassed
      5alpha(beta)-androstanes and 3-oxo-androst-4-enes. Major positions of
      hydroxylation in these were C(2), C(6), C(11), C(16) and C(18). Additional oxo
      groups were common at C(6), C(11) and C(16). We conclude that the presence of
      multiple further oxygenated metabolites of androstenedione in urine from neonates
      with 21-hydroxylase deficiency and their pattern indicate a predominance of the
      classical pathway of androgen synthesis and reflect an increased demand for
      clearance. The positions of oxygenation in androstane(ene)s are dependent on the
      configuration at C(3)-C(5).

PMID- 22974829
TI  - Normal values for respiratory muscle strength in healthy preschoolers and school
      children.
AB  - AIM: To generate reference values for respiratory muscle strength in healthy
      children aged three to twelve years. METHODS: Participants were recruited from
      three schools and selected after a respiratory disease questionnaire analysis and
      written informed consent by parents or guardians. All participants included in
      the study had normal spirometry, height and weight were measured on the same day.
      Respiratory muscle strength was evaluated by a single examiner following the
      guidelines for pulmonary function tests. The association between MIP and MEP
      values with the potential predictive variables was analyzed using a multiple
      linear regression model. RESULTS: A total of 171 participants were selected and
      distributed evenly by age. The age, height, weight and forced vital capacity
      showed moderate to strong correlations with both respiratory pressures. However,
      the regression model showed that height and weight were the best variables to
      predict MIP in both sexes, and age and weight to predict MEP. The power of
      prediction (R2) ranged from 46 to 58%. The intraclass correlation coefficient was
      used in a subgroup and demonstrated excellent reproducibility between tests.
      CONCLUSION: The results of this study demonstrate that the behavior of
      respiratory muscle strength in healthy preschool and school children can be
      explained by age, height and weight.

PMID- 22974830
TI  - Infliximab therapy modulates an antigen-specific immune response in chronic
      beryllium disease.

PMID- 22974831
TI  - Cigarette smoking and airway wall thickness on CT scan in a multi-ethnic cohort:
      the MESA Lung Study.
AB  - BACKGROUND: Autopsy studies show that smoking contributes to airway wall
      hyperplasia and narrowing of the airway lumen. Studies of smoking and airway
      measures on computed tomography (CT) scan are limited to case-control studies of
      measures that combine airway lumen and wall thickness. OBJECTIVES: We
      hypothesized that cumulative cigarette smoking would be associated with increased
      airway wall thickness in a large, population-based cohort. METHODS: The Multi
      Ethnic Study of Atherosclerosis enrolled participants age 45-84 years from the
      general population. Smoking history was assessed via standardized questionnaire
      items; current smoking was confirmed in half the cohort with cotinine. Airway
      lumen and wall thickness were measured in two dimensions in posterior basal
      segmental bronchi on cardiac-gated CT scans. Analyses were adjusted for age,
      gender, genetic ancestry, education, height, weight, asthma history, particulate
      matter, scanner type, and scanner current. RESULTS: Half of the 7898 participants
      had smoked and 14% were current smokers. Pack-years of smoking were associated
      with thicker airway walls (mean increase 0.002 mm per ten pack-years [95% CI:
      0.00002, 0.004] p = 0.03). Current smoking was associated with narrower airway
      lumens (mean decrease -0.11 mm [95% CI: -0.2, -0.02] p = 0.02). There was no
      evidence that either association was modified by genetic ancestry, and findings
      persisted among participants without clinical disease. CONCLUSIONS: Long-term
      cigarette smoking was associated with subclinical increases in wall thickness of
      sub-segmental airways whereas current smoking was associated with narrower airway
      lumen diameters. Smoking may contribute to airway wall thickening prior to the
      development of overt chronic obstructive pulmonary disease.

PMID- 22974833
TI  - Efficient reduction of serum cholesterol by combining a liver-targeted gene
      delivery system with chemically modified apolipoprotein B siRNA.
AB  - Apolipoprotein B (Apo B) is a key amphipathic glycoprotein compound in the
      metabolism of plasma lipoproteins (mainly very low-density lipoprotein (VLDL) and
      LDL). Inhibition of Apo B synthesis by short interfering RNA (siRNA) targeting
      Apo B (Apo B siRNA) is very efficient for serum LDL reduction. In the present
      study, the chemically modified Apo B siRNA (Apo B-siBNA) with the increased
      enzymatic stability was selected. We developed a cationic conjugate for efficient
      delivery of Apo B-siBNA into the liver by introducing pullulan with different
      molecular weights (MWs) (5900 and 107,000) into polyethylenimine (PEI).
      Introduction of pullulan into PEI dramatically decreased mortality and lung
      damage after systemic injection of the conjugate/Apo B-siBNA complexes into mice.
      The PEI-pullulan carrier prepared with high MW pullulan (107,000) was more stable
      in the blood stream and showed higher fluorescence levels in the liver for a
      longer time than the carrier prepared with low MW pullulan (5900). Moreover,
      efficient reduction of serum LDL and Apo B mRNA in the liver was observed in mice
      injected with PEI-pullulan (MW, 107,000)/Apo B-siBNA, whereas there was no or
      little change in serum LDL and Apo B mRNA in livers of mice treated with Apo B
      siBNA alone, PEI/Apo B-siBNA, and PEI-pullulan (MW, 5900)/Apo B-siBNA. These
      results suggest that combining a liver-targeted gene delivery system with
      chemically modified Apo B siRNA efficiently reduces the level of serum LDL and
      Apo B mRNA in the liver.

PMID- 22974832
TI  - Antioxidant protection by PECAM-targeted delivery of a novel NADPH-oxidase
      inhibitor to the endothelium in vitro and in vivo.
AB  - Oxidant stress caused by pathological elevation of reactive oxygen species (ROS)
      production in the endothelial cells lining the vascular lumen is an important
      component of many vascular and pulmonary disease conditions. NADPH oxidase (NOX)
      activated by pathological mediators including angiotensin and cytokines is a
      major source of endothelial ROS. In order to intercept this pathological pathway,
      we have encapsulated an indirect NOX inhibitor, MJ33, into immunoliposomes (Ab
      MJ33/IL) targeted to endothelial marker platelet endothelial cell adhesion
      molecule (PECAM-1). Ab-MJ33/IL, but not control IgG-MJ33/IL are specifically
      bound to endothelium and attenuated angiotensin-induced ROS production in vitro
      and in vivo. Additionally, Ab-MJ33/IL inhibited endothelial expression of the
      inflammatory marker vascular cell adhesion molecule (VCAM) in cells and animals
      challenged with the cytokine TNF. Furthermore, Ab-MJ33/IL alleviated pathological
      disruption of endothelial permeability barrier function in cells exposed to
      vascular endothelial growth factor (VEGF) and in the lungs of mice challenged
      with lipopolysaccharide (LPS). Of note, the latter beneficial effect has been
      achieved both by prophylactic and therapeutic injection of Ab-MJ33/IL in animals.
      Therefore, specific suppression of ROS production by NOX in endothelium,
      attainable by Ab-MJ33/IL targeting, may help deciphering mechanisms of vascular
      oxidative stress and inflammation, and potentially improve treatment of these
      conditions.

PMID- 22974834
TI  - A method for inducing antigen-specific IgG production by in vitro immunization.
AB  - In vitro immunization (IVI) possesses a number of advantages over conventional
      immunization. However, the number of positive clones derived from IVI is limited,
      and the affinity of the antibodies from derived clones is relatively low.
      Moreover, the majority of immunoglobulins produced in culture are IgMs instead of
      IgGs, which limits the application. Here, we report an improved protocol for IVI
      using mouse spleen cells. This protocol consists of multiple cycles of repeated
      antigen stimulation followed by cell expansion, which increases the frequency of
      plasma cells that produce antigen-specific IgG antibodies. The culture
      conditions, including the cell density, the type of stimulants, and the initial
      cell preparation, were found to be important for inducing the IgG response. In
      addition, an analysis of the genes and cytokines expressed during the IVI showed
      that the antigen-specific B cells were specifically activated via CD4-positive
      helper T cells. As evidence for this concept, our IVI protocol enabled us to
      establish an IgG antibody against keyhole limpet hemocyanin with a dissociation
      constant in the order of 10(-7)M.

PMID- 22974835
TI  - Isotype analysis of gerbil-mouse heterohybridomas by RT-PCR.
AB  - We designed primer sets specific to the immunoglobulin (Ig) heavy-chain constant
      region (IGHC) genes in Mongolian gerbil (Meriones unguiculatus) to amplify five
      gerbil IGHC cDNA sequences, CMU, Cgamma1, Cgamma2, Cepsilon, and Calpha. Five
      gerbil-mouse heterohybridomas B11D2(C2), B11E2(D5).M, B5-3, D5, and C11
      respectively expressed Cgamma1, CMU, Cgamma2, Cgamma2, and Cgamma1. In contrast,
      a commercial isotyping kit for mouse Igs identified Cgamma1, CMU, Cgamma3,
      Cgamma3, and Cgamma1, respectively, misidentifying gerbil IgG2 as IgG3 by cross
      reactivity with anti-mouse IgG3 polyclonal antibody. These primer sets will allow
      the accurate estimation of gerbil Ig classes and IgG subclasses. These results
      from three gerbil strains indicate that the primer sets can be used for isotype
      analysis of gerbil mAbs and for evaluation of humoral immunity.

PMID- 22974836
TI  - Development and applications of simultaneous immunochemical staining and serial
      detection of overlapping proteins in blotting procedures.
AB  - Immunoblotting techniques are widely used for specific protein identifications
      and characterizations. The specific bindings of antibodies to epitopes in a
      protein sequence permits determination of antigens and gives detailed information
      about protein compositions and expression levels in complex suspensions. However
      the techniques are mostly restricted to one specific antibody determination.
      Overlaying proteins are detected using numerous repeated gel runs. For multiple
      but specific protein determinations on one immunoblot, here we describe the
      detection of several antigens by simultaneous incubation of antibodies originated
      from different species followed by sequential addition of secondary antibodies
      labelled with horseradish peroxidase (HRP) and binding to analogous primary
      antibodies. Particular signals were visualized step by step using a HRP
      chemiluminescence substrate while enzymatic HRP reactions were meanwhile
      inactivated irreversibly by hydrogen peroxide incubation. We demonstrate flexible
      applications of multiple antigen detections using the Western blotting technique
      with determination of the CNS protein markers neuron specific enolase, glial
      fibrillary acid protein and the physiological prion protein (PrP(C)) in brains
      and in meats as food contaminations and with glycotyping of PrP(C) using
      antibodies binding to different epitopes. We showed the use of the dot blotting
      technique with serial determination of different antigens in complex protein
      suspensions. The method is easy to handle and is flexible and applicable in the
      fields of diagnostics and public health for detection of overlaying proteins on
      one immunoblot.

PMID- 22974837
TI  - Characterizing and quantifying leukocyte populations in human adipose tissue:
      impact of enzymatic tissue processing.
AB  - Adipose tissue inflammation is a major mechanistic link between obesity and
      chronic disease. To isolate and characterize specific leukocyte populations, e.g.
      by flow cytometry, tissue needs to be processed to digest the extracellular
      matrix. We have systematically compared the impact of different commonly used
      collagenase preparations, digestion times, and normalization strategies on the
      reproducibility of flow cytometric phenotyping of adipose tissue leukocyte
      populations. Subcutaneous adipose tissue was obtained from 11 anonymous donors
      undergoing elective procedures at a plastic surgery clinic in Seattle, WA. We
      found that collagenase alone consistently produced better cell yields (p=0.007)
      than when combined with additional proteases such as the commercially available
      liberases. Moreover, liberase significantly degraded the cell surface expression
      of CD4 (p<0.001) on T cells and to a lesser extent CD16 (p=0.058) on neutrophils.
      Extension of the digestion interval from 30 to 120 min did not significantly
      impact cell viability (p=0.319) or yield (p=0.247). Normalization by either 'live
      gate' or percentage of CD45(pos) leukocytes exhibited the lowest coefficient of
      variation for tissue digests between 60 and 75 min, compared to normalization per
      gram of tissue, which consistently exhibited the greatest variability. Our data
      suggest that digestion of adipose tissue using pure collagenase for 60-75 min
      provides the best cell yield and viability, with minimal degradation of cell
      surface markers used to identify immune cell subpopulations, and best
      reproducibility independent of the normalization strategy.

PMID- 22974838
TI  - Caffeine suppresses lipopolysaccharide-stimulated BV2 microglial cells by
      suppressing Akt-mediated NF-kappaB activation and ERK phosphorylation.
AB  - Since the anti-inflammatory effect of caffeine is unclear in microglial cells, we
      performed whether caffeine attenuates the expression of pro-inflammatory
      mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Caffeine
      substantially suppressed the LPS-induced pro-inflammatory mediators nitric oxide
      (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha) in
      BV2 microglial cells. These effects resulted from the inhibition of their
      regulatory genes inducible NO synthase (iNOS), cycloxygenase-2 (COX-2) and TNF
      alpha. In addition, caffeine significantly decreased LPS-induced DNA-binding
      activity of nuclear factor-kappaB (NF-kappaB) by suppressing the nuclear
      translocation of p50 and p65 subunits. A specific NF-kappaB inhibitor,
      pyrrolidine dithiocarbamate (PDTC), attenuated the LPS-induced expression of
      iNOS, COX-2 and TNF-alpha genes. In addition, we elucidated that inhibition of
      Akt phosphorylation plays a crucial role in caffeine-mediated NF-kappaB
      regulation in LPS-stimulated BV2 microglial cells. Caffeine also attenuated the
      LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and a
      specific inhibitor of ERK, PD98059, subsequently downregulated the expression of
      the pro-inflammatory genes iNOS, COX-2 and TNF-alpha. Taken together, our data
      indicate that caffeine suppresses the generation of pro-inflammatory mediators,
      such as NO, PGE(2) and TNF-alpha as well as their regulatory genes in LPS
      stimulated BV2 microglial cells by inhibiting Akt-dependent NF-kappaB activation
      and the ERK signaling pathway.

PMID- 22974839
TI  - Relevance and challenges in modeling human gastric and small intestinal
      digestion.
AB  - Gastric and small intestinal (GSI) models are increasingly used as an alternative
      to in vivo assays to answer many questions raised by industry and researchers. A
      broad range of in vitro systems is available, from static monocompartmental to
      dynamic multicompartmental models. However, these models require a compromise
      between technological complexity and biological significance. Further efforts and
      technological innovations are still needed to improve in vitro models and meet
      growing demands in the areas of nutrition and health. This review describes the
      models available to date for the human stomach and small intestine and highlights
      their relevance in nutritional, toxicological, pharmaceutical, and
      microbiological studies. Limitations and challenges facing artificial digestion
      technology are also discussed.

PMID- 22974840
TI  - NEDD4 is overexpressed in colorectal cancer and promotes colonic cell growth
      independently of the PI3K/PTEN/AKT pathway.
AB  - Ubiquitination controls multiple cellular processes relevant to cancer
      pathogenesis. Using Gene Set Enrichment Analysis of an mRNA transcriptome
      dataset, we have identified genes encoding components of the ubiquitin system
      that are differentially expressed in colorectal cancers as compared to normal
      colonic mucosa. Among the significantly overexpressed genes was NEDD4 (neural
      precursor cell-expressed developmentally down-regulated 4), the prototype member
      of the HECT (homologous to E6AP C-terminus) E3 ubiquitin ligase family. Previous
      studies have shown that NEDD4 may act as an oncoprotein by inducing
      ubiquitination and degradation of the tumor suppressor protein PTEN (phosphatase
      and tensin homolog). To investigate its functional importance in colorectal
      cancer, HCT-15 and LoVo colon cancer cells were depleted of NEDD4 by small
      interfering RNA. The depletion resulted in reduced growth and altered cell
      morphology in both cell lines. However, NEDD4 depletion did not affect the PTEN
      protein level or PI3K/AKT signaling pathway activation. Moreover, ectopic
      expression of NEDD4 did not influence the PTEN subcellular localization or
      protein level. Collectively, these data demonstrate that NEDD4 is overexpressed
      in colorectal cancers, and suggest that NEDD4 promotes growth of colon cancer
      cells independently of PTEN and PI3K/AKT signaling.

PMID- 22974841
TI  - The body adiposity index is not the best hip-height index of adiposity.

PMID- 22974843
TI  - Kidney allocation for transplantation: some aspects of ethics and comparative
      law.
AB  - The allocation of organs is a crucial ethical issue. The importance attached to
      different allocation criteria differs considerably among the various national and
      international organizations. The balance between justice-centered and utility
      centered systems is shifting and there are signs of a possible swing away from
      systems centered mainly on waiting times to others centered mainly on criteria of
      utility. This evolution is very significant and seems to run counter to the main
      stream of modern bioethics. Examples from different national policies are given
      herein. Particular attention is given to Europe, where national bioethics
      committees have tended to ignore the aspect of organ allocation. By
      overemphasizing the issues related to informed consent, the ethical challenges
      arising from the problems of resource allocation are often relegated to second
      place.

PMID- 22974844
TI  - Research for optimization in organ donation in a macro-area after federal reform
      of the Italian health system.
AB  - Law number 91, dated April 1, 1999, established an organizational model for the
      activities of donation, retrieval, and transplantation of organs consisting of 4
      levels: national, interregional, regional, and local. After 12 years this
      organizational project, called the "National Transplant Network," has reached an
      excellent level of effectiveness and efficiency. Since 2001 regional
      administrative districts have been entrusted increasingly with responsibilities
      concerning health. In 2008 health federalism was approved and in 2010 the federal
      health fiscal system entered in force. In a country with a federal organization,
      where regional districts are completely autonomous, is there a reason to still
      have a national transplant center and 3 interregional transplantation centers? We
      have developed a hypothesis on the function of Interregional Transplant Centers
      (CIR). The risk of federalism is the fragmentation of the National Healthcare
      System. To adequately meet the needs of citizens, smaller regions should sign
      agreements with larger regions regarding transplantation programs that require a
      large pool of donors whereas they could retain management of patients during the
      presurgery and postsurgery phases. The CIR should be committed to increase organ
      donation, to establish shared protocols and procedures, to disseminate knowledge,
      and to ensure equal access to health care. In conclusion, the adoption of health
      and fiscal federalism provides an opportunity to build healthcare systems to
      optimize resources. The network model should be kept but it is necessary to
      overcome localism and create positive federalism.

PMID- 22974845
TI  - Living organ donation, a therapeutic possibility, is still poorly used in Italy:
      a national analysis.
AB  - Validity of living donor kidney transplantation is universally accepted. In
      contrast, after enthusiastic adoption in the 1990s, living donor liver
      transplantation has decreased in recent years. The aim of the present study was
      to evaluate retrospectively the current use of this form of donation in Italy by
      comparing liver and kidney cadaveric and living donations from 2002 to 2010. The
      number of liver transplantations from living donors has decreased from 34 in 2002
      (3.9% of total) to 13 in 2010 (1.3% of total). In contrast, kidney
      transplantation from living donors increased from 126 (7.9% of total) to 186 (11%
      of total). We observed that living donations for kidney transplantation are still
      underused, especially with unrelated donors. Living donor liver transplantation
      has decreased in recent years; this procedure should be reserved to centers with
      particular expertise. It would be appropriate to implement programs to increase
      the attention of health professionals and the general population and to integrate
      living donations into programs of deceased organ donation.

PMID- 22974846
TI  - Glasgow coma score and tumor necrosis factor alpha as predictive criteria for
      initial poor graft function.
AB  - Initial poor graft function (IPGF) is a major factor influencing the clinical
      outcome after liver transplantation (LT), but there is no reliable method to
      assess and predict graft dysfunction. To help clinicians determine prognosis in
      the early postoperative period, individual parameters and complex scoring systems
      have been suggested, but most of them are inaccurate because of the
      multifactorial nature of transplantation courses. Therefore, the aim of our study
      was to retrospectively evaluate predictive criteria for retransplantation. Forty
      two patients were enrolled in this study: 18 who experienced primary non-function
      (PNF) and 24 with delayed graft function (DGF). All of the patients were treated
      with the Molecular Adsorbent Recirculating System (MARS). They were into 3
      subgroups: patients who survived without LT (n = 20; 47.7%); patients who
      underwent LT (n = 16; 37%), and patients who died before transplantation (n = 6;
      14%). Stepwise multivariable logistic regression analysis was performed with the
      intent to find the risk factors for LT or death after MARS treatment (second
      analysis). Receiver operating characteristic (ROC) curves were performed on
      significant variables in the logistic regression model with the intent to
      individually predict variables for LT or death. After a stepwise multivariable
      logistic regression analysis enrolling all of the previously reported features
      only 2 variables, tumor necrosis factor (TFN)-alpha and Glasgow coma score (GCS)
      score, were statistically significant. TNF-alpha was an unique independent risk
      factor for retransplantation or death after MARS treatment (odds ratio [OR]
      1.235; P = .013). Conversely, GCS score was protective against retransplantation
      or death (OR 0.150; P = .003). Starting from these assumptions, a predictive
      model was created using these 2 variables. On ROC analysis, the combined score
      showed an area under the curve greater than that of the 2 variables considered
      separately. Validating these results with a larger number of patients, we
      considered these 2 factors as subjective parameters to determine outcomes and the
      difference between PNF and DGF.

PMID- 22974847
TI  - Extracorporeal lung perfusion and ventilation to improve donor lung function and
      increase the number of organs available for transplantation.
AB  - INTRODUCTION: Ex vivo lung perfusion (EVLP) has been validated as a valuable
      technique to increase the pool of organs available for lung transplantation.
      MATERIAL AND METHODS: After a preclinical experience, we obtained permission from
      the Ethics Committee of our institution to transplant lungs after EVLP
      reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure
      (PaO(2))/fraction of inspired oxygen (FiO(2)) <= 300 mm Hg were considered to be
      inclusion criteria, whereas the presence of chest trauma and lung contusion,
      evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease
      were exclusion criteria. We only considered subjects on an extra corporeal
      membrane oxygenation (ECMO) bridge to transplantation with rapid functional
      deterioration. Using Steen solution with packed red blood cells oxygenated with
      21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of
      approximately 40% predicted cardiac output. Once normothermic, the lungs were
      ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory
      rate of 7 bpm. Lungs were considered to be suitable for transplantation if well
      oxygenated [P(v-a) O(2) > 350 mm Hg on FiO(2) 100%], in the absence of
      deterioration of pulmonary vascular resistance and lung mechanics over the
      perfusion time. RESULTS: From March to September 2011, six lung transplantations
      were performed, including two with EVLP. The functional outcomes were similar
      between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm
      Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP
      versus conventional). Intensive care unit ICU and hospital length of stay were
      similar (P = .533 and P = .663, respectively) with no mortality at 60 days in
      both groups. EVLP donors were older (49 +/- 6 y versus 21 +/- 7 y, P < .05), less
      well oxygenated (184 +/- 6 mm Hg versus 570 +/- 30, P < .05), displaying higher
      Oto scores (9.5 +/- 0.7 versus 1.7 +/- 1.5, P < .05). CONCLUSIONS: The first 6
      months of the EVLP program allowed us to increase the number of organs available
      for transplantation with short-term outcomes comparable to conventional
      transplantations.

PMID- 22974848
TI  - Use of the Oto lung donor score to analyze the 2010 donor pool of the Nord Italia
      Transplant program.
AB  - INTRODUCTION: The feasibility and utility of a lung donor score that has been
      recently proposed was tested among a pool of lung donors referred to the Nord
      Italia Transplant program (NITp) organ procurement organization. MATERIAL AND
      METHODS: Each lung donor was assigned an Oto score including, age, smoking
      history, chest X-ray, secretions and ratio of arterial oxygen tension to inspired
      oxygen fraction (PaO(2)/FiO(2)). Based on clinical compromise, each variable
      received a score between 0 and 3, except for PaO(2)/FiO(2), which was scored
      between 0 and 6 given its overall relevance. RESULTS: Throughout 2010, 201
      multiorgan donors were initially considered to be potential lung donors. Among
      these, 59 (29.4%) eventually yielded 67 lung transplantations (named "Used
      group"). Among the 142 (70.6%) refused lungs, 28 were not used due to logistic or
      medical problems ("general exclusion" group, GE) and 114, because of poor lung
      function ("lung exclusion" group, LE). Median lung donor scores were 1 (range, 0
      to 3), 4 (range, 2.5 to 6.5), and 7 (range, 5 to 9) in the Used, GE, and LE
      groups, respectively (one-way analysis of variance, P < .001). Some donors with
      Oto scores <=7 worsened over time so that the score had significantly increased
      by the time of organ retrieval. Overall, subjects who died after lung
      transplantation were characterized by higher lung donor scores, (2 [1-4] versus
      0.5 [0-3], P = .003). CONCLUSION: Our analysis suggested that the use of a donor
      score as a dynamic tool over the donation process was of great utility to
      describe and analyze a pool of lung donors.

PMID- 22974849
TI  - Strategies to increase heart transplantation in centre-sud transplant
      organization.
AB  - The 21 heart transplantations in Centre-Sud Transplant Organization (OCST) is a
      stable number despite increasing donations, especially among subjects aged 50 to
      60 years. The aim of the present study was to evaluate the possibility to
      increase the usage of marginal hearts through dipyridamole ecostress. From 2008
      to 2010 we analyzed OCST donors at 74 donation sites for echocardiography (31 yes
      versus 43 no) and heart utilization: (1) principal sites (n > 13) versus (2)
      minor sites (n < 13). Among 2145 signaled donors, there were 900 (42%) effective
      donors, including 816 (38%) utilized organs from 387 subjects of age <50 years;
      189, 50 to 60 years and 240, >60 years with 217 (90%); 24 (10%), and 3 (1%)
      utilized hearts respectively to the analyzed sites, the utilized donors with
      echocardiography were 373: 259 (69.4%) versus 114 (30.5%) from those without such
      a service. Utilized donors between 50 and 60 years came from principal sites (n =
      50), minor sites (n = 7) or those without an echocardiagram (n = 16). Utilized
      heart donors in each type of site were eight, one, and six, respectively. We
      believe that it may be possible to increase the total number of heart
      transplantations using dipyridamole stress-test echocardiography at the sites
      with major retrieval activity to increase heart transplantation among donors in
      the age range of 50 to 60 years.

PMID- 22974850
TI  - Preliminary study of early histomorphometric changes in hepatic steatosis.
AB  - The first endpoint of this study was to find new markers that document the
      progression of hepatic steatosis through quantitative histomorphometric analysis
      in the absence of hemodynamic changes. The second endpoint was to start building
      a mathematical database to help to achieve a score in the future. For this study
      we enrolled 130 random patients, including 10 with normal histology despite
      suspected disease, 70 positive for steatosis, 20 affected by nonalcoholic steato
      hepatitis, and 30 with hepatitis virus C or B-related cirrhosis. One hundred
      thirty images were analyzed for a total of 1,320 sinusoids. Each image was
      processed with a custom program written with the use of the Vision toolbox of the
      Labview platform, following a semiautomated procedure. The mean sinusoidal areas
      (SAs) and percentage fractions of parenchymal area occupied by sinusoids (SA/PA)
      were subdivided into 3 groups. Finally, we analyzed the form of sinusoids,
      approximating them to an ellipse, to be able to define the relationship between
      the 2 axes with the aim of proposing a parameter, "local hydraulic resistance"
      (LHR), that was proportional to the resistance to blood flow within the bounds of
      the histologic specimen. Among the images, we observed a difference in the size
      of SAs among the 3 groups of patients, namely, normal, steatotic of different
      stages, and cirrhotic patients. In fact, there was evidence of a reducted SA when
      steatosis was <30%, with an average value of 0.0032 mm(2), patients with
      steatosis of 30%-50% showed an average SA of 0.0024 mm(2), and there was a
      further reduction among subjects with steatosis grades >50% (mean 0.0017 mm(2)).
      The LHR value showed that the morphometric parameter SA/PA could be
      quantitatively interpreted also as a functional impairment relative to the
      increased resistance opposing blood flow in pathologic conditions.

PMID- 22974851
TI  - Italy-Greece cooperation for transplantation of medically urgent Greek patients:
      is it an effective, efficient model?
AB  - INTRODUCTION: In 2005 the Italian National Transplant Centre (CNT) signed a
      cooperation agreement with the Hellenic Transplant Organization (HTO) fostering
      the transfer and transplantation of urgent Greek liver patients at Italian
      transplantation centers. So as to not reduce access to transplantation for
      Italian patients, the agreement provided compensation for organs allocated to
      Greek transplant recipients. The aim of this study was to analyze the flow of
      patients from Greece to Italy and the number of received livers to consider the
      possibility to extend this kind of agreement to other countries, so that this
      should not penalize Italian recipients. MATERIALS AND METHODS: The agreement
      provides the possibility for Greek patients affected by acute disease to be
      transferred to Italian transplantation centers participating in the agreement.
      Until 2008 livers transplanted into Greek recipients were returned through a
      preferential offer of surplus Greek organs, whereas from 2009 an obligation of
      payback was introduced. RESULTS: During the reviewed period requests for
      transfer, transferred patients, and number of patients who later underwent
      transplantation in Italy were 56, 26, and 23, respectively. Livers offered by the
      Greek organization that were accepted, transferred, and transplanted in Italy
      have been 82, 50, and 44, respectively. DISCUSSION AND CONCLUSIONS: According to
      our analysis, the cooperation has had as positive impact for both Greece, which
      has difficulties transplanting urgent recipient because of the low number of
      donors, and for Italy, which is not penalized by the use of an organ in a Greek
      recipients, but is also rewarded for helpfulness.

PMID- 22974852
TI  - Organ donors with small renal cancer: report of 3 cases.
AB  - Transmission of donor malignancies has been reported since the early days of
      clinical transplantation. Up to 1995, the Transplant Tumor Registry created by
      Penn included 155 cadaver and 29 living donor affected by tumors. The most
      common, excluding brain tumor, was renal cell carcinoma (RCC). RCC represents 2%
      of adult cancers, an incidence that increases with advancing age. The expansion
      of the criteria that define a suitable organ donor has as a consequence included
      donors that are older than in the past. Small RCCs are found during renal
      recovery from a cadaveric donor in ~1% of cases. The use of such donors is a
      matter of debate; it has been suggested that donor kidneys with small RCC Fuhrman
      grade I/II may be transplanted after appropriate surgical excision. We report our
      experience with 3 donors with clear cell RCC: 2 contralateral kidneys were
      transplanted in 2 recipient and a third recipient received an affected kidney
      after a wide tumor excision. All of the patients we alive and free from
      recurrence at 14-48 months (mean 35 mo). In the third case, immunosuppression was
      achieved with a mammalian target of rapamycin inhibitor, which is currently used
      not only as an immunosuppressant to prevent rejection, but also as treatment for
      renal cancer. Our data confirmed that donors with small renal tumors may be used,
      because the risk of tumor recurrence is small and the benefits of a kidney
      transplantation are great.

PMID- 22974853
TI  - The use of neoplastic donors to increase the donor pool.
AB  - The aim of the study was to evaluate the experience of the Centre-Sud Transplant
      Organization (OCST) area using cadaveric donor with neoplastic diseases to
      evaluate the possibility of transmission to recipients. From January 1, 2003, to
      December 31, 2010, the neoplastic risk has been reported to be 5.4% (377/4654
      referred donors). In 2003, the number of donors with a tumor and their mean age
      were respectively: 60 (10.3%) and 59.6 +/- 19.9; 2004: 33 (5.2%) and 61.4 +/-
      15.9; 2005: 32 (6%) and 62.8 +/- 15.5; 2006: 46 (7%) and 60.7 +/- 19.1; 2007: 51
      (7%) and 58.9 +/- 16; in 2008: 58 (7%) and 59.7 +/- 19.6; 2009: 47 (7%) and 57 +/
      26; 2010: 49 (7%) and 64 +/- 16. The organ most affected by tumor has been the
      central nervous system (18%). The tumor was diagnosed before in 325 (86%) cases,
      versus during organ retrieval in 48 (12.7%) donor operations but before, which
      four cases (1%) occured after transplantation. According to the histological
      types and grades, 28 evaluated donors (8.2%) were suitable for transplantation.
      The histological types were: thyroid carcinoma (n = 3); prostate carcinoma (n =
      8), renal clear cell carcinoma (n = 7), oncocytoma (n = 1), meningiomas (n = 2),
      dermofibrosarcoma (n = 1); verrucous carcinoma of the vulva (n = 1), colon
      adenocarcinoma (n = 1), grade II astrocytoma (n = 1), adrenal gland tumor (n =
      1), gastric GIST (n = 1), oligodendroglioma (n = 1). Forty-five organs were
      retrieved (22 livers, 19 kidneys, 3 hearts, and 1 pancreas) and transplanted into
      44 recipients with 1 liver-kidney combined transplantation. Four recipients died
      due to causes not related to the tumor. No donor-transmitted tumor was detected
      among the recipients. Donation is absolutely not indicated in cases of tumors
      with high metastatic potential and high grades. Performing an accurate evaluation
      of the donor, taking into account the histological grade, currently can allow,
      organ retrieval and transplantation with an acceptable risk.

PMID- 22974854
TI  - Model for end-stage liver disease dynamic stratification of survival benefit.
AB  - Only patients with Model for End-stage Liver Disease (MELD) scores >=18 or >=17
      experience a survival benefit (SB) at 12 and 36 months after liver
      transplantation (OLT). The SB calculation estimates the difference after
      stratification for risk categories between the survival rate of transplanted
      versus waiting list patients. The aim of this study was to perform a short- and
      long-term (60 months) SB analyses of a Italian OLT program. One-hundred seventy
      one patients were stratified into four MELD classes (6-14, 15-18, 19-25, 26-40),
      and two groups: namely, waiting list (WL) and transplanted groups (TX). The
      median waiting time for transplanted patients was 4.4 months (range, 0-35). SB
      was expressed as mortality hazard ratio (MHR) as obtained through a Cox
      regression analysis using as a covariate the status of each patient in the
      waiting list (WL = 0, reference group) or the TX group (TX = 1). Values over 1
      indicated the MHR in favor of the WL with the values below 1 indicating MHR in
      favor of Tx. In the MELD class 6 to 14, the MHR was above 1 at 3 and 6 months,
      indicating an SB in favor of WL; subsequently, the MHR dropped below 1,
      indicating an SB in favor of TX (P < .05). In the MELD class 15 to 18 the MHR was
      above 1 at 3 months, but below 1 subsequently (P < .05). For MELD classes 19 to
      25 and 26 to 40, the MHR was always below 1 (P < .01). According to the SB
      approach, patients in the MELD class 6 to 14 could safely wait for at least 36
      months; patients in the MELD class 15 to 18 should likely remain no longer than
      12 months on the waiting list, and all the remaining patients with MELD > 18
      should be transplanted as soon as possible. OLT should not be precluded but only
      postponed for MELD < 19 patients.

PMID- 22974855
TI  - A preliminary European study on extended-criteria liver donation and transplant
      recipient consent.
AB  - ELPAT (Ethical, Legal, and Psychologic Aspects of Organ Transplantation)
      coordinated the distribution to European liver transplant centers of an
      electronic questionnaire regarding the definition of extended-criteria liver
      donation (ECD) and its implication for informed consent by transplant recipients.
      Completed questionnaires were received from 30 centers in 13 countries including
      28 who accepted ECD liver donors. The criteria to define a liver donor as ECD
      were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%);
      serum sodium >165 mmol/L in 17 centers (60%); ICU stay with ventilation >7 days
      in 16 centers (57%); serum glutamic oxaloacetic transaminas >90 U/L, in 12
      centres (42%); body mass index >30 kg/m(2) in 10 centers (35%); serum glutamate
      pyruvate transaminase >105 U/L in 10 centers (35%); serum bilirubin >3 mg/dL in
      10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers
      informed the transplant candidate of the ECD status of the donor: 10 (43%) when
      the patient registered for transplantation, 3 (14%) when an ECD liver became
      available, and 10 (43%) on both occasions. Ten centers required the liver
      transplant candidate to sign a special consent form. Ten centers informed the
      potential recipient of the donor's serology. Only 3 centers informed the
      potential recipient of any high-risk behavior of the donor.

PMID- 22974856
TI  - Predictive value of the Charlson comorbidity index in kidney transplantation.
AB  - BACKGROUND: Nonimmunologic factors have been recently implicated in worse
      outcomes after kidney transplantation, producing a need to predict the operative
      risk among kidney recipients. We assessed the predictive value of the Charlson
      comorbidity index (CCI) among kidney transplant recipients. METHODS: A
      retrospective study of 223 first deceased-donor kidney transplantations performed
      from 2000 to 2007 evaluated the role of comorbidities. RESULTS: About 50% of
      recipients displayed >1 comorbid condition before transplantation; the most
      frequently reported was diabetes mellitus. Increasing CCI scores significantly
      affected graft and patient survivals. Crude analysis showed a significant
      association between CCI >1 and risk of death (hazard ratio [HR], 3.87; 95%
      confidence interval [CI], 1.06-14.06; P = .04). After adjustment for several
      covariates, high CCI values remained significantly predictive of
      posttransplantation outcomes with a HR for death of (12.53; 95% CI, 1.9-82.68; P
      = .009). CONCLUSIONS: Our predictive model showed a strong association of CCI and
      patient survival even after adjustment for several clinical covariates. CCI may
      be used to evaluate patients referred for kidney transplantation who display a
      significant burden of comorbid conditions that increase the risk of premature
      death or graft loss.

PMID- 22974857
TI  - The role of obesity in kidney transplantation outcome.
AB  - BACKGROUND: The number of obese kidney transplant candidates has been growing.
      However, there are conflicting results regarding to the effect of obesity on
      kidney transplantation outcome. The aim of this study was to investigate the
      association between the body mass index (BMI) and graft survival by using
      continuous versus categoric BMI values as an independent risk factor in renal
      transplantation. METHODS: We retrospectively reviewed 376 kidney transplant
      recipients to evaluate graft and patient survivals between normal-weight,
      overweight, and obese patients at the time of transplantation, considering BMI as
      a categoric variable. RESULTS: Obese patients were more likely to be male and
      older than normal-weight recipients (P = .021; P = .002; respectively). Graft
      loss was significantly higher among obese compared with nonobese recipients.
      Obese patients displayed significantly lower survival compared with nonobese
      subjects at 1 year (76.9% vs 35.3%; P = .024) and 3 years (46.2% vs 11.8%; P =
      .035). CONCLUSIONS: Obesity may represent an independent risk factor for graft
      loss and patient death. Careful patient selection with pretransplantation weight
      reduction is mandatory to reduce the rate of early posttransplantation
      complications and to improve long-term outcomes.

PMID- 22974858
TI  - Polyomavirus BK infection in end-stage renal disease: analysis of viral
      replication in patients on hemodialysis or peritoneal dialysis.
AB  - Patients in end-stage renal disease undergoing renal replacement treatment (ESRD
      RRT) are considered immunocompromised. The hemodialysis (HD) or peritoneal
      dialysis (PD) procedures seem to produce alterations of the immune status.
      Interest in immunosuppression has increased due to the poliomavirus BK (BKV)
      infection. Our study evaluated the prevalence of BKV infection in ESRD-RRT
      patients and viral replication on HD or PD. From 2006 to 2011 we selected 58
      patients (34 males) in ESRD-RRT for inclusion in our study. BKV replication was
      evaluated by qualitative real-time polymerase chain reaction. In ESRD-RRT
      patients, the prevalence of BKV replication on plasma was 21%. We identified two
      groups of patients according to the dialysis procedure: 36 patients on HD (HD
      group) and 22 on PD (PD group). BKV replication in the HD group was 33% (12 of
      36) versus 0% (0 of 22) in the PD group. Different age, number of months on RRT,
      and preserved diuresis was observed in the HD versus PD groups. With our results
      we can speculate that BKV infection in ESRD-RRT patients is linked to factors
      involved in the uremia-related immune dysfunction but also to specific mechanisms
      related to the different RRTs. PD is an option that could be associated with a
      better transplant outcome for patients undergoing kidney transplantation.

PMID- 22974859
TI  - Laparoscopic placement of "self-locating catheter": our experience and a review
      of literature.
AB  - Among the available devices for peritoneal dialysis, the Di Paolo self-locating
      catheter (SLC) represents a milestone using to its ability to ensure a permanent
      reliable means of access to the peritoneum. Our experience included 20
      laparoscopic peritoneal catheter placements from 2008 to 2011. We performed the
      laparoscopic surgical technique using 3 trocars: 2 10 mm and 1 5 mm. The
      technique allows catheter introduction into the pouch of Douglas under direct
      vision. Among 20 treated patients, 1 died due to causes unrelated to peritoneal
      dialysis; 1 underwent transplantation, and 1 was switched to hemodialysis because
      of ultrafiltration failure. The complications included 2 catheter displacements,
      only 1 of them needing repositioning by open laparotomy, and 1 case of
      peritonitis. No infection in the subcutaneous tunnel or obstruction and
      malfunction occurred among our patients. The Di Paolo SLC is similar to Tenckhoff
      catheter but includes a small tungsten cylinder at the tip that engenders
      continuous gravity in the peritoneal cavity, producing a reduced risk of
      dislocation. In a large series of cases, Di Paolo et al. reported a 0.8%
      dislocation rate after SLC placement compared with 12% using Tenckhoff catheters.
      They also demonstrated a reduced risk of other complications, such as
      peritonitis, infection, obstruction, and failure. These data have been confirmed
      by other authors with smaller case series. Thus, introduction of the SLC and
      improved surgical techniques result in better efficiency of peritoneal dialysis.

PMID- 22974860
TI  - Correlational study between psychic symptoms and quality of life among
      hemodialysis patients older than 55 years of age.
AB  - BACKGROUND: The loss of renal function and urination with dialysis can produce a
      strong emotional crisis in a patient. This study explored the correlation between
      psychic symptoms and quality of life among hemodialysis patients who were older
      than 55 years of age in relation to demographic characteristics of age, time on
      dialysis, and education. PATIENTS AND METHODS: Twenty patients undergoing
      hemodialysis were included in the study. The psychic symptoms were studied using
      the Symptom Checklist-90. Revised (SCL-90 R) and the quality of life was studied
      using the Complete Form Health Survey (SF 36). RESULTS: The high correlation
      between psychological sizes investigated through the SCL-90 R test and those for
      the SF-36 test confirmed the close relationship between physical disorders and
      mental suffering, and reduced vitality, and lack of socialization. CONCLUSION:
      The psychiatrist and psychologist may help hemodialysis patients to improve their
      quality of life by providing new coping strategies for each of the family,
      occupational, and social network.

PMID- 22974861
TI  - Delayed graft function and long-term outcome in kidney transplantation.
AB  - BACKGROUND: There are still many controversies about the impact of delayed graft
      function (DGF) on kidney transplantation outcome. The aims of this study were to
      define factors associated with DGF and to ascertain the relative impact of DGF on
      kidney transplantation outcome, both in the early postoperative period and in
      long-term follow-up. PATIENTS AND METHODS: Four hundred kidney transplant
      recipients were reviewed to assess the clinical impact of DGF on long-term
      outcome. RESULTS: The overall prevalence of DGF was 24.3%. DGF was significantly
      associated with increasing recipient and donor age, duration of dialysis, and
      cold ischemia time. Patients with DGF displayed a significantly worse graft (P =
      .005) and patient (P < .001) survival compared with recipients with immediate
      function. CONCLUSION: DGF is a frequent complication of renal transplantation and
      may be associated with a reduced graft and even patient survival. Strategies to
      prevent graft injury and, more specifically, DGF may be an important clue to
      provide a better long-term outcome in kidney transplantation.

PMID- 22974862
TI  - Magnetic resonance with diffusion-weighted imaging in the evaluation of
      transplanted kidneys: updating results in 35 patients.
AB  - BACKGROUND: We compared values of apparent diffusion coefficient (ADC) with renal
      function indices among a population of kidney transplant recipients who underwent
      magnetic resonance with diffusion-weighted imaging (DWI) of their grafts.
      MATERIALS AND METHODS: Thirty-five patients with right iliac transplanted kidneys
      were studied using 1.5-T magnetic resonance. Diffusion echo-planar sequences with
      several b-values were acquired to investigate transplanted grafts. Patients were
      divided into 3 groups according to their creatinine clearances; Group A,
      clearance >60 mL/min; Group B, clearance >30 and <=60 mL/min; and Group C,
      clearance <=30 mL/min. ADC values between groups were compared using Mann-Whitney
      U test. Receiver operating characteristic (ROC) curves were used to predict the
      normal function (Group A) versus renal failure cohorts (Group C). RESULTS:
      Comparing mean values of ADC between Group A and Group C patients, we observed a
      significant difference (P = .0003) with higher ADC values among patients with a
      normal creatinine clearance (>60 mL/min). Comparing Groups B and C did not show a
      significant difference (P = .05); nor did Group A and Group B reveal a
      significant difference (P = .38). To predict normal clearance values, the Group A
      ROC curve showed an area under curve (AUC) of 0.780 with a sensitivity of 92.3%
      and a specificity of 68.2% at a threshold ADC value of >=2.08 * 10(-3) mm(2)/sec.
      In the prediction of low clearance values, the Group C ROC curve showed an AUC of
      0.846 with a sensitivity of 83.3% and a specificity of 82.6% using a threshold
      ADC value of <=2.07 * 10(-3) mm(2)/sec. CONCLUSIONS: Updating our experience
      among 35 patients, DWI was confirmed to be a promising noninvasive tool to assess
      renal function; an ADC >=2.08 * 10(-3) mm(2)/sec may be used as a threshold to
      predict a normal clearance. However, an overlap of ADC values between groups is a
      limit.

PMID- 22974863
TI  - Pretransplant and protocol biopsies may help in defining short and mid-term
      kidney transplant outcome.
AB  - Although many variables may affect long-term graft survival no biomarker is
      available to identify donor kidney with poor quality and with inadequate short
      and long-term outcome. While in marginal donors pre-transplant renal biopsies are
      commonly performed to establish if donor kidneys are suitable for transplantation
      they are not performed in standard donors. In this study we assessed the
      relevance of pre-transplant morphological features on post-transplant renal
      function and evaluated the association between perioperative parameters with
      posttransplant histological and clinical findings. Kidney transplant recipients
      undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12
      months were enrolled in the study. Perioperative and posttransplant clinical and
      biochemical parameters were recorded. Semiquantitative analysis of PAS stained
      kidney sections was used to determine the degree of lesions. Glomerular volume
      was measured by computed morphometry. A strong inverse correlation was found
      between donor age and renal graft function at 1, 6, and 12 months after
      transplantation. A prompt functional recovery was associated with a better renal
      function at 6 months and one year. Kidneys with higher glomerular volume
      demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial
      grading at protocol biopsies was associated with a poor renal function at 1
      month. Our findings confirm the importance of donor age in kidney transplant long
      term outcome and demonstrate that pretransplant and protocol biopsies are valid
      options to determine graft outcome and to define therapeutic strategies and
      tailor immunosuppressive regimen for each patient.

PMID- 22974864
TI  - Kidney transplantation from living donors genetically related or unrelated to the
      recipients: a single-center analysis.
AB  - Living-donor programs have gradually become an attractive strategy to expand the
      donor pool for kidney transplantation (KT). Grafts from living-related donors
      (LRD) display superior function and longer survival than those obtained from
      cadaveric sources. Recent reports have shown that outcomes from living-unrelated
      donors (LUD) are not worse than those from LRD. In this study, we evaluated 135
      procedures using living donors performed in our center between 1987 and 2010
      (LRD: n = 111; LUD: n = 24). Among the LRD, most donors were mothers (n = 61;
      54.95%), fathers (n = 25; 22.52%), and sisters (n = 16; 14.41%). The LUD included
      wives (n = 17; 70.83%) and husbands (n = 7; 29.17%). The mean recipient ages for
      LRD versus LUD were 26.94 +/- 13.51 and 50.04 +/- 8.86 years, respectively (P <
      .0001). The recipient female/male distribution was 33/78 (29.73%/70.27%) for the
      LRD versus 6/18 (25%/75%) for the LUD group (P = .643). The donor age was 48.79
      +/- 9 years in LRD and 49.25 +/- 8.44 years in LUD (P = .696). The donor
      female/male distribution was 72/39 (64.86%/35.16%) in LRD and 17/7
      (70.83%/29.17%) in LUD (P = .576). The follow up was 123.79 +/- 87.87 months
      (range, 0.91-279.93). Overall patient and graft survivals were 94.1% and 67.6%,
      respectively. There was no significant difference in patient survival after
      stratifying for donor type (LRD: 93.9%; LUD: 95.8%; P = .961) or in graft
      survival after stratifying for donor type (LRD: 63.8%; LUD: 87.8%; P = .124).
      Entering donor type as an independent variable in a univariate Cox regression, we
      observed no significance for either recipient (P = .961) or graft survival (P =
      .142). The results of this study suggest that LUD utilization should be
      encouraged in KT programs.

PMID- 22974865
TI  - Glomerular c4d immunoreactivity in acute rejection biopsies of renal transplant
      patients.
AB  - In renal transplant patients, glomerulitis may be present in all types of acute
      rejection, often accompanied by diffuse C4d staining of peritubular capillaries:
      C4d3 positivity in more than 50% of peritubular capillaries. It may progress to
      chronic transplant glomerulopathy, characterized by capillary basement membrane
      multilayering, proteinuria, and progressive loss of renal function. While C4d3 is
      a recognized marker of an antibody-mediated reaction, the significance of
      glomerular C4d (GlC4d) staining is unknown. The aim of this study was to evaluate
      GlC4d immunoreactivity and its correlation with C4d3 in acute rejection biopsies.
      Paraffin-embedded acute rejection biopsies from 90 renal transplant patients were
      evaluated according to the Banff classification. Biopsies showing C4d-positive
      endothelial cells in more than 50% of glomeruli were considered GlC4d-positive.
      C4d3-positive staining prevalence was 23%. GlC4d-positive staining showed an 89%
      concordance rate (r = 0.81, P < .0001; Cohen's k = 0.80, P < .0001). GlC4d
      detection sensitivity was 0.80 and specificity 0.97. C4d3 and GlC4d
      immunoreactivity was significantly associated with glomerulitis (P < .006 and P <
      .03, respectively) and with proteinuria at the time of biopsy (P < .03 and P <
      .01, respectively). Interestingly, GlC4d positivity correlated better than C4d3
      positivity with the presence of posttransplant circulating anti-human leukocyte
      antigen alloantibodies (P < .04 and P = .7, respectively). Patients with C4d3- or
      GlC4d-positive acute rejections underwent graft loss due to interstitial fibrosis
      and tubular atrophy more frequently than those with C4d0- or GlC4d-negative
      rejections (P < .0001 and P < .005, respectively), whereas no differences were
      observed in graft loss due to death. In conclusion, C4d3 and GlC4d stains showed
      a high correlation rate. Compared with C4d3, GlC4d staining demonstrated good
      sensitivity and excellent specificity. Our results suggested that GlC4d staining
      may indicate glomerular endothelial damage and be of prognostic value.

PMID- 22974866
TI  - Cardiovascular risk factors in renal transplant patients after switch from
      standard tacrolimus to prolonged-release tacrolimus.
AB  - Cardiovascular (CV) diseases are the leading cause of death after renal
      transplantation. Renal transplant patients present CV risk factors that correlate
      with renal function and the use of immunosuppressive drugs. Noncompliance with
      immunosuppressive therapy after organ transplantation increases the incidence of
      rejection, graft loss, and patient death. A simple posology regimen is the best
      way to promote compliance with prescribed therapy. To meet this need, a new
      formulation of tacrolimus that is suitable for once-daily administration, is now
      available on the market: prolonged-release tacrolimus (Fkpr). We analyzed changes
      in CV risk factors observed in renal transplant patients after transition from
      standard tacrolimus (Fk) to Fkpr and the rate of patients with the investigated
      parameters within the normal ranges before and after conversion. The study
      enrolled 40 Caucasian renal transplant patients (26 men and 14 women) who were
      being followed at our posttransplantation day hospital clinics. After a varying
      time interval after transplantation, patients on treatment with tacrolimus,
      mycophenolate + mofetil (MMF), and steroid entered a 12-month observation period.
      Thereafter, they were switched to Fkpr, also in association with MMF and steroid,
      and were observed for a further 12-month period. The following parameters were
      tested in all patients: creatinine, creatinine clearance, insulin resistance,
      total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, uric acid,
      homocysteine, and urine magnesium. The switch from Fk to Fkpr showed an
      improvement of the parameters investigated. Moreover, the proportion of patients
      with normal laboratory values after the transition from Fk to Fkpr was noted
      either to increase or to remain stable at the improved levels observed during
      therapy with Fk. Immunosuppressive treatment with Fkpr represents an even better
      option than Fk for renal transplant patients, because by reducing CV risk factors
      it favorably affects the long-term outcomes for graft and patient.

PMID- 22974867
TI  - Long-term interleukin-2 assessment after conversion from a twice-daily to once
      daily tacrolimus regimen in stable kidney recipients.
AB  - Conversion to tacrolimus (Tac) to once daily (Tac-O) formulation is commonly
      followed by a 20% reduction in Tac trough levels in the first month. It is not
      associated with modifications of renal function but there is the issue of its
      effects on inflammatory cytokines and on subclinical rejection. The aim of our
      study was to evaluate long-term interleukins (IL)-2 profiles in stable renal
      transplant patients after Tac-O conversion. We enrolled 10 stable kidney
      transplant patients converted to Tac-O. Tac trough levels, serum creatinine
      concentrations, glomerular filtration rate using the Modification of Diet in
      Renal Disease formula, C-reactive protein, IL-2 levels, and clinical assessments
      were performed monthly for 6 months before and 12 months after conversion.
      Despite the significant reduction in Tac trough levels, we did not observe
      alterations suggestive of clinical or subclinical acute rejection.

PMID- 22974868
TI  - The pregnancy rate and live birth rate after kidney transplantation: a single
      center experience.
AB  - Kidney transplantation is the treatment of choice for end-stage renal disease
      (ESRD). Kidney transplantation recipients live longer and have better quality of
      life than patients on dialysis. Hypothalamic gonadal dysfunction in females who
      have ESRD may be reversed within the first few months after kidney
      transplantation, such as the ability to have children. Despite thousands of
      successful pregnancies in transplantation recipients, there is limited
      information about it. In this study, we evaluated the pregnancy rates and live
      birth rates in women (n = 133) who underwent kidney transplantation in our center
      from 1983 to 2010. Recipients of a second kidney transplantation and recipients
      of multiorgan transplantations were excluded. We observed 33 pregnancies with 11
      live births (33.3%), 12 spontaneous abortions (36.36%), and 10 therapeutic
      abortions (30.3%). The pregnancy rate was 18%. The live birth rate was 33.3%.
      Therapeutic abortions were 36.3%, and the pregnancies resulting in fetal loss
      were 30.3%. The pregnancies were identified in 32 women. The majority of women (n
      = 32; 96.9%) had a single pregnancy, whereas 1 woman (3.1%) had two pregnancies.
      In our series, the pregnancy rates for kidney transplantation recipients were
      markedly lower and decreased more rapidly than those reported in the general
      population.

PMID- 22974869
TI  - Cytomegalovirus and gastric cancer after renal transplantation: a possible
      interplay.
AB  - We herein have described a case of de novo gastric cancer in a renal transplant
      recipient with a concomitant diagnosis of gastrointestinal cytomegalovirus (CMV)
      disease. We hypothesize that CMV, through causing an imbalance between cell
      proliferation and cell death, functions as the causative agent for the
      progression of the gastric tumor in this case after gastric colonization. To the
      best of our knowledge, this is the second such case ever reported of such kind
      and may represent a platform for investigations aimed at understanding the
      possible interplay between CMV and gastric cancer.

PMID- 22974870
TI  - Effects of continuous erythropoietin receptor activator (CERA) in kidney
      transplant recipients.
AB  - Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in
      kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin
      receptor activator (CERA) has been one of the newest recombinant ESAs to treat
      anemia in dialysis and nondialysis patients with chronic kidney disease. The
      efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We
      evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We
      enrolled 19 anemic KTRs (60 +/- 9.3 y) who were treated with short-acting ESA for
      >=24 weeks. They were shifted to the equivalent dose of CERA and followed for 24
      weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and
      transferrin. To investigate tolerance to and satisfaction with short-acting ESA
      and CERA, questionnaires were administered to the patients before shifting to
      CERA and at the end of the follow-up. After 6 months, CERA induced an increase in
      hemoglobin levels (12.3 +/- 0.8 vs 11.2 +/- 1.1 g/dL; P = .002, CERA vs short
      acting ESA, respectively). In 2 patients treatment was discontinued because the
      hemoglobin increased to >13 g/dL. No significant differences were observed in
      serum iron and creatinine between short-acting ESA and CERA throughout the study.
      The questionnaires showed better compliance to CERA treatment with reduced pain
      at the injection site, which led subjects to prefer CERA to short-acting ESA. In
      summary, CERA showed better control of anemia compared with short-acting ESA. It
      was preferred by the majority of patients, mainly because of the reduced number
      of monthly injections. Our results demonstrated CERA to be effective, safe, and
      well tolerated in the management of anemia in KTRs.

PMID- 22974871
TI  - Encapsulating peritoneal sclerosis after kidney transplantation: a single-center
      experience from 1982 to 2010.
AB  - Encapsulating peritoneal sclerosis (EPS), a severe complication of long-term
      peritoneal dialysis (PD), produces a 50% mortality rate. EPS is characterized by
      progressive and excessive fibrotic thickening of the peritoneum, leading to
      encapsulation of the bowel and intestinal obstruction which may present after
      kidney transplantation (KT), a condition known as posttransplantation EPS. In
      this study we reviewed 1,500 KT performed in our center from 1982 to 2010,
      seeking to evaluate the influence of EPS incidence on kidney recipient and graft
      survival. We detected severe posttransplantation EPS among 16 adult single-kidney
      cadaveric-donor recipients. The EPS patients (age, 46.68 +/- 10.62 years;
      female/male 5/11) were initially compared with a strictly selected group (n = 48)
      of non-EPS patients (age, 46.35 +/- 10.26 years; female/male, 18/30). Peritoneal
      dialysis (PD) duration was significantly higher in the EPS group (47.75 +/- 9.77
      vs. 25.87 +/- 10.43 months; P < .0001). This relationship was not only evident on
      univariate analysis, but also in a multivariate logistic regression model that
      entered previously selected variables: age (P = .518), sex (P = .796), serum
      creatinine (P = .441), estimated glomerular filtration rate (P = .566), and
      diagnostic category (P = .804). Diagnostic plots confirmed the reliability of the
      logistic regression models. In conclusion, EPS which negatively influences the
      outcome and quality of life of kidney recipients, was related to PD duration
      before to KT.

PMID- 22974872
TI  - Allograft nephrectomy: what is the best surgical technique?
AB  - BACKGROUND: The objective of this study was to evaluate differences in outcomes
      of allograft nephrectomies performed by extracapsular versus intracapsular
      techniques. METHODS: From 1993 to 2010, we performed 89 allograft nephrectomies,
      including 57 by extracapsular techniques and 32 by intracapsular, chosen
      according to feasibility at the beginning of the surgery. Fisher exact test and
      logistic regression were used for statistical analysis. Survival estimates after
      allograft nephrectomy were calculated according to the Kaplan-Meier method.
      RESULTS: After a mean graft survival of 49.7 months, the indications for
      transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%),
      infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%),
      renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time,
      blood loss, transfusions, and complications were similar between the
      extracapsular and intracapsular groups. The only difference in surgical aspects
      between the 2 groups was the mean hospital stay, which was longer for the
      extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by
      multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0-1.1; P =
      .03). CONCLUSIONS: Our experience showed no significant advantages in favor of
      the intracapsular technique except for a shorter length of hospital stay than
      after the extracapsular procedure.

PMID- 22974873
TI  - Conversion from calcineurin inhibitors to everolimus with low-dose cyclosporine
      in renal transplant recipients with squamous cell carcinoma of the skin.
AB  - Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in renal
      transplant recipients. Conversion to mammalian target of rapamycin inhibitors
      after diagnosis of SCC may reduce the incidence of recurrence of skin cancer.
      This retrospective study evaluated the outcome of renal transplant recipients
      followed by the Renal Unit with posttransplant diagnosis of SCC treated with
      conversion from calcineurin inhibitors (CNIs) to Everolimus (EVR) associated with
      low-dose cyclosporine. Eleven patients developed SCC at a median time from renal
      transplantation of 107 months (range 36-264). Five patients with creatinine
      clearance (CCl) below 40 mL/min before conversion developed end stage renal
      disease (two cases) or further deterioration of renal function (two cases); only
      one patient in this group maintained a stable renal function. The remaining six
      patients with a CC1 greater than 40 mL/min and proteinuria below 0.8 g/24 hours
      maintained a stable renal function after conversion to EVR at a median follow-up
      of 22 months (range 15-75). Conversion from CNIs to EVR has been proven safe,
      effective, and associated with low recurrence of SCC in patients with a CCl >40
      mL/min. In the case of preexisting deterioration of renal function or significant
      proteinuria, conversion to EVR should be carefully evaluated.

PMID- 22974874
TI  - Contrast-enhanced ultrasound assessment of complex cystic lesions in renal
      transplant recipients with acquired cystic kidney disease: preliminary
      experience.
AB  - We prospectively studied the potential value of contrast-enhanced ultrasound
      (CEUS) to characterize complex acquired cystic kidney disease (ACKD) or suspected
      solid renal masses, avoiding the risk of inducing acute kidney injury in 138
      renal transplant recipients by contrast-enhanced computed tomography (CT). Forty
      three cases (31%) had ACKD; 15 ACKD patients (35%) showed suspicious or
      nondiagnostic ultrasound. The latter subgroup underwent CEUS and, if the
      suspicion was confirmed, a contrast-enhanced CT. Thirty five lesions were
      identified in the 15 patients studied by CEUS. According to the Bosniak
      classification, 27 cysts were type I (BI), four type II (BII), two type III
      (BIII) with enhancement at the level of thickened septa; we also identified two
      solid enhancing lesions (BIV). We followed the BI and BII lesions with serial
      CEUS, while the remaining four cases underwent contrast-enhanced CT showing two
      solid lesions and two complex cysts with contrast enhancement in the septea. The
      four patients underwent surgical resection yielding three renal cell carcinomas
      one papillary carcinoma as the pathological findings. This preliminary study
      characterized solid nodules and BIII lesions for further evaluation by CT. CEUS
      seems to correctly characterize BI and BII cysts that are not clearly defined by
      standard ultrasound.

PMID- 22974875
TI  - Liver autotransplantation for the treatment of unresectable hepatic metastasis:
      an uncommon indication-a case report.
AB  - Ex situ ex vivo liver surgery represents a method to expand the surgical
      indications to treat otherwise unresectable liver tumors. We report the case of a
      38-year old woman with hepatic metastasis from a pancreatoblastoma that was
      judged to be unresectable due to the involvement of the three hepatic veins. To
      treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant
      chemotherapy, and thermal ablation of a liver metastasis. After appropriate
      preoperative study and with the permission of the ethics committee, she underwent
      ex situ ex vivo liver resection. The hepatectomy was performed by removing the
      whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was
      reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic
      resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The
      two hepatic veins were reconstructed using patches of saphenous vein. The organ
      was preserved continuously for 6 hours using hypothermic perfusion with 4 degrees
      C Celsior solution. The liver was then reimplanted performing an anastomosis
      between the reconstructed hepatic veins and the caval prostheses. The patient was
      discharged at postoperative day 22 and is currently disease-free at 8 months
      after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver
      surgery offers an additional option for patients with both primary and secondary
      liver tumors considered to be unresectable using traditional surgical approaches.

PMID- 22974876
TI  - Polyomavirus BK infection before liver transplantation in patients with chronic
      kidney disease.
AB  - End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both
      immunocompromised populations but polyomavirus BK (BKV) replication before liver
      transplantation is rare. We evaluated BKV prevalence among liver transplant
      recipients with renal dysfunction and the possible role of CKD as a risk factor
      for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients
      awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22;
      18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis
      of viremia evaluated using quantitative real-time polymerase chain reactions. The
      prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group
      (Fisher test; P = .027). We hypothesized that the presence of CKD may represent
      an additional condition of immunologic dysfunction regarding antiviral
      surveillances other than the antibacterial one that characterizes ESLD
      immunodysfunction, which could have promoted BKV replication. The specific
      immunologic mechanisms involved in pretransplantation diseases may have a role in
      BKV reactivation that could become responsible for nephropathy after
      transplantation.

PMID- 22974877
TI  - Side-to-side cavocavostomy in adult piggyback liver transplantation.
AB  - OBJECTIVE: Our objective was to perform a retrospective study that described the
      anastomosis technique as well as the complications of side-to-side cavo-caval
      reconstruction. PATIENTS AND METHODS: From June 1998 to April 2011, we performed
      284 liver transplantations including 10 adults with live donor organs. In all
      cases but 2 (272), cavo-caval reconstruction was performed using side-to-side
      cavo-caval (STSCC) anastomosis. In 19 cases (6.9%), we also carried out an end-to
      side temporary porto-caval shunt (TPCS). In 17 cases (6.2%) the technique was
      performed for retransplantation. RESULTS: STSCC anastomosis was technically
      feasible in all but 2 cases, regardless of the recipient's vena cava, anatomic
      factors, or graft size. Mean operative time for the STSCC was 13 minutes (range,
      6-25). Routine Doppler ultrasonography was performed intraoperatively at the end
      of the surgery. There was no case of cava stump thrombosis. Complications
      associated with this technique were limited to 2 patients. One complication was
      torsion due to donor graft/recipient mismatch, which was successfully treated
      surgically by falciform ligament fixation. The second complication was only
      evident by sinusoidal congestion and was managed nonoperatively. Seventeen cases
      were uneventful for retransplant recipients. CONCLUSIONS: STSCC during piggyback
      liver transplantation is safe and can be performed in the retransplantation
      setting, with a low incidence of venous outflow obstruction that can be
      associated with the traditional piggyback technique. Our data suggest that donor
      graft to recipient mismatch is not an absolute contraindication when proper body
      size match is considered. A wide anastomosis with typical recipient hepatic vein
      inclusion is warranted with routine postanastomotic Doppler ultrasonography.

PMID- 22974878
TI  - Everolimus and enteric-coated mycophenolate sodium ab initio after liver
      transplantation: midterm results.
AB  - BACKGROUND AND AIM: Everolimus (EVR) use in liver transplantation (OLT) has been
      prescribed with calcineurin inhibitors (CNIs), steroids, and monoclonal
      antibodies. The aim of our study was to evaluate the safety, feasibility, and
      impact on renal function of EVR ab initio, in combination with enteric-coated
      mycophenolate sodium (EC-MPS) without the use of induction treatment, steroids,
      or CNIs. PATIENTS AND METHODS: We retrospective analyzed nine consecutive
      patients who underwent OLT at our institution. The initial dose of EVR (1.5 mg/d)
      was adjusted to achieve trough levels of 8 to 12 ng/mL. EC-MPS introduced at 1080
      mg/d was maintained at the same dose over time. RESULTS: At a mean follow-up of
      21.48 (standard deviation [SD] 1.4) months from OLT, 7/9 recipients were alive
      with stable graft function. The 2-year patient and graft survivals were 77%. One
      recipient died due to cerebral hemorrhage and one, lung failure. No clinical
      evidence of an acute rejection episode was observed. Mean estimated glomerular
      filtration rate value, according to the Modification of Diet in Renal Disease
      formula increased from 59.5 (SD 9.89) mL/min/1.73 m(2) at OLT to 100.2 (SD 47.5)
      mL/min/1.73 m(2) (P = .03) after 12 months and 98.71 (SD 33.74) mL/min/1.73 m(2)
      (P = .03) after 24 months' follow-up. CONCLUSION: A double immunosuppression
      therapy with EVR and EC-MPS ab initio seemed to be efficacions and safe,
      representing a valid alternative to CNIs to prevent renal failure after OLT.

PMID- 22974879
TI  - Management of hepatitis C virus infection in liver transplantation with adacolumn
      apheresis.
AB  - Recurrent hepatitis C virus (HCV) is a major cause of liver transplant loss,
      hepatic failure, and retransplantation need. Posttransplantation antiviral
      therapy in patients with evidence of recurrent disease is the mainstay of
      management. Although HCV is a hepatocellular pathogen, there is increasing
      evidence that the virus can infect and persist in other cells. In particular,
      granulocytes and monocytes/macrophages are known to constitute extrahepatic sites
      for HCV replication and dissemination. The aim of this study was to apply
      Adacolumn apheresis as a possible therapeutic alternative to conventional drug
      therapy to manage HCV infections. Seven patients who underwent liver
      transplantation for HCV-related cirrhosis were eligible for the study. The
      patients underwent 5 1-hour sessions for 5 consecutive days. The first treatment
      was performed in the anhepatic phase of liver transplantation with the intent to
      early reduce infected granulocytes and monocytes/macrophages. The patients were
      evaluated over the 5 days after inclusion with 3- and 6-months follow-ups. Early
      apheresis treatments in the anhepatic phase and over the following 4 days after
      transplantation produced low viral loads in 4 patients, negative viral loads in 2
      patients, and increased viremia in 1 patient. At follow-up, the viremia load was
      stable in 6 patients without increased transaminase levels. At the end of the
      treatment cycle, almost all immune cells of the 6 patients maintained CD4+/CD8+ T
      cell ratios. The optimal timing of treatment initiation is unknown, but early
      preemptive therapy is recommended to decrease the risk for recurrent infection.
      Although this study investigated the responses among a small number of patients,
      it documented that the Adacolumn changed cellular immunity, promoting early
      virologic responses.

PMID- 22974880
TI  - Stages of early acute renal dysfunction in liver transplantation: the influence
      of graft function.
AB  - The development of early acute renal dysfunction (eARD) occurring in the first
      week after orthotopic liver transplantation (OLT) is mainly influenced by more
      severe degrees of pre-OLT hepatic insufficiency and liver graft dysfunction. The
      aim of our study was to evaluate the incidence of eARD post-OLT as well as its
      association with pre- and post-OLT hepatic dysfunction. We selected 54 end-stage
      liver disease patients who underwent OLT from 2008 to 2011. The prevalence of
      eARD was 53.7% (29/54) classified according to AKIN criteria in ARD-Risk (55.2%),
      ARD-Injury (27.6%) and ARD-Failure (17.2%). The worst stage of post-OLT eARD
      (eARD-Failure) seems to be influenced by the poor pre-OLT hepatic function as
      well as by early suboptimal recovery of graft function.

PMID- 22974881
TI  - Occurrence of chronic renal failure in liver transplantation: monitoring of pre-
      and posttransplantation renal function.
AB  - The aim of our study was to evaluate the occurrence of middle and long-term
      chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in
      relation to acute renal failure (ARF). We prospectively monitored 75 patients,
      studying renal function on the basis of serum creatinine and glomerular
      filtration rate as estimated using the Modification of Diet in Renal Disease
      formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was
      56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29%
      stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5%
      (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The
      occurrence of CRF before OLT was 14.7%. We did not find any association between
      ARF and post-OLT CRF. The most relevant result of our study was the association
      between CRF at 6 and 12 months after transplantation with pre-OLT CRF on
      univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal
      function should always be considered in the follow-up of liver transplant
      patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for
      post-OLT CRF, representing important criterion to define specific therapeutic
      interventions to reduce patient morbidity and mortality.

PMID- 22974882
TI  - Outcomes of liver transplantation in simultaneously hepatitis B surface antigen
      and hepatitis C virus RNA positive recipients: the deleterious effect of donor
      hepatitis B core antibody positivity.
AB  - BACKGROUND: Recent data from Italian studies have shown excellent results of
      liver transplantation (LT) in hepatitis B virus (HBV)-infected patients with
      grafts from hepatitis B core antibody (HBcAb)-positive donors, whereas such
      grafts in hepatitis C virus (HCV)-infected recipients have displayed poorer
      outcomes. We investigated the results of LT with HBcAb-positive grafts in
      patients with ongoing HBV and HCV coinfections. METHODS: From August 1999 to
      December 2009, we performed 27 adult primary LTs from deceased heart-beating
      donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA
      positivity simultaneously: 12 patients received a graft from an HBsAg-negative
      HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core-D
      group). Immunosuppression included a calcineurin inhibitor, antimetabolite and
      steroids which were suspended at 6 months. Anti-HBV prophylaxis was always
      perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues. RESULTS: The
      groups were similar regarding variables of donor, recipient, donor-recipient
      match, LT procedure, and acute rejection treatment. Median follow-up for
      surviving grafts was 67 months (range, 16-141). Among all patients, HCV-RNA
      remained positive after LT. The prevalence of histologically proven recurrent HCV
      hepatitis was similar in the 2 groups: 83% core+D vs 73% core-D. No recurrent HBV
      hepatitis occurred during the follow-up. Graft survival at 5 years was
      significantly lower in the core+D group (core+D 48% vs core-D 87%; P = .018), in
      which a significantly higher prevalence of graft loss was caused by HCV
      recurrence (core+D 5/12, 42% vs core-D 1/15, 7%; P = .03). All of the 5 core+D
      patients who lost their grafts due to HCV recurrence did not receive anti-HCV
      therapy (4 owing to an aggressive disease and 1 because of patient refusal).
      CONCLUSIONS: Outcomes of LT in patients with ongoing HBV and HCV coinfection are
      adversely affected by donor HBcAb positivity, an effect that is mainly mediated
      by the dismal course of HCV recurrence after LT.

PMID- 22974883
TI  - Outcomes of liver transplantation from hepatitis B core antibody-positive donors
      in viral cirrhosis patients: the prevailing negative effect of recipient
      hepatitis C virus infection.
AB  - BACKGROUND: Liver transplantation (LT) with grafts from hepatitis B core antibody
      (HBcAb)-positive donors has been the object of recent studies, suggesting
      different outcomes depending on the etiology of viral cirrhosis in the recipient.
      METHODS: From November 2002 to December 2009, we transplanted 124 livers from
      hepatitis B surface antigen (HBsAg)-negative HBcAb-positive deceased heart
      beating donors to adult recipients with viral cirrhosis, classified as: HBsAg
      positive (group 1; n = 63); hepatitis C virus (HCV) RNA positive (group 2; n =
      52); and simultaneously HBsAg and HCV-RNA positive (group 3; n = 9).
      Immunosuppression included a calcineurin inhibitor, mycophenolate, and steroids
      (tapered to suspension in 6 months). In all groups, anti-HBV prophylaxis was
      performed with anti-HBs immunoglobulins and nucleos(t)idic analogues. RESULTS:
      The groups were similar regarding donor, recipient, donor-recipient match,
      transplant procedure, variables, and treatment of acute rejection, except for
      younger recipient age in group 1 (P = .009), lower recipient body mass index in
      group 3 (P = .03), and longer cold ischemia time in group 2 (P = .003). Median
      follow-up for surviving grafts was 63 (range, 16-102) months. No case of
      recurrent or de novo hepatitis B occurred. The prevalence of histologically
      proven recurrent HCV hepatitis was similar in groups 2 and 3 (65% vs 78%). Graft
      survival at 5 years was 86% in group 1, 35% in group 2, and 31% in group 3 (P <
      .0001 for group 1 vs 2; P < .01 for group 1 vs 3). On multivariate analysis,
      independent predictors of worse graft survival were HCV infection in the
      recipient (HR 8.08, 95% CI 3.36-17.97; P < .0001) and MELD at LT >=25 (HR 3.72,
      95% CI 1.12-12.37; P = .032). CONCLUSIONS: The presence of HCV infection in the
      recipient is the factor which most negatively influenced the outcome of LT using
      grafts from HBcAb-positive donors. Allocation of such grafts should consider the
      type of viral cirrhosis among LT candidates.

PMID- 22974884
TI  - Safety of polymyxin-B-based hemoperfusion in kidney and liver transplant
      recipients.
AB  - Infection represents one of the primary barriers to successful organ
      transplantation. Our principal end point was to use a new assay, Entotoxin
      Activity Assay (EAA), which was developed to rapidly detect endotoxin activity
      (EA) for an early diagnosis of this complication. We also sought to prove the
      validity and safety of endotoxin removal using polymyxin-B-based hemoperfusion
      (PMX-DHP). The criterion for inclusion in the study was suspected infection when
      a patient experienced at least 2 of the 4 criteria of the systemic inflammatory
      response syndrome. EAA was performed on 71 patients: 29 liver transplantations
      and 42 kidney transplantations. Twenty-eight patients (39.5%) with EA >0.60
      underwent PMX-DHP treatment to remove endotoxins. Each treatment was performed
      for 2 hours with a blood flow of 100 mL/min. All of the patients were treated
      with PMX-DHP until achieving an EA <0.4. Stabilization of hemodynamic and
      inflammatory frameworks was observed after the PMX-DHP. At 30 days follow-up, all
      of the patients were alive with good graft function and low levels of EA. We
      think it might be useful to determine EA routinely in transplant patients and
      look forward to large multicenter clinical trials to accurately assess the
      benefits of the EAA plus DHP-PMX to treat transplant patients with sepsis.

PMID- 22974885
TI  - Bacterial bloodstream infections in liver transplantation: etiologic agents and
      antimicrobial susceptibility profiles.
AB  - Liver transplantation (OLT) is a lifesaving procedure for the treatment of many
      end-stage liver diseases, but infection and acute rejection episodes still remain
      the main causes of morbidity and mortality. Bloodstream infections (BSIs),
      particularly, are the major cause of mortality among these patients. BSIs in OLT,
      are from intra-abdominal, biliary, respiratory, urinary, wound and/or central
      venous catheter sources. A certain percentage are of unknown origin. Using the
      computerized database of our microbiology laboratory, we analyzed all BSIs in 75
      consecutive adult liver transplant patients in a single center between January
      2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had
      a single; two, two episodes, and the other six patients each >4 episodes. All
      episodes occurred in the first 60 days following OLT; the majority (74%), in the
      first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the
      most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were
      gram-positive, the most frequent being coagulase-negative staphylococci,
      particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were
      resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25%
      the panding-resistant phenotype. There was a high incidence of gram-negative and
      most importantly, resistant bacteria, which required appropriate therapy. These
      data showed that it is imperative to promote strategies to prevention and contain
      antimicrobial resistance.

PMID- 22974886
TI  - Role of liposomal amphotericin B prophylaxis after liver transplantation compared
      with fluconazole for high-risk patients. impact on infections and mortality
      within one year.
AB  - BACKGROUND: Fungal infections are still one of the most important issue in liver
      transplant patients, contributing considerably to both morbidity and mortality.
      Few studies have been published comparing antifungal protocols for their impact
      on liver transplant (OLT) patients. The aim of this study was to evaluate the
      effects of liposomal amphotericin B compared with fluconazole prophylaxis on
      morbidity and mortality after liver transplantation. METHODS: We evaluated all 44
      patients undergoing OLT from January 2006 to January 2009 who were enrolled and
      randomized to undergo treatment with Amphotericin B (3 mg/kg/d; group A = 25
      patients) or fluconazole (800 mg Loading dose and thereafter 400 mg/d according
      to renal parameters and immunosuppressant trough levels; group B = 18 patients)
      for at least 7 to 14 days with 12 months follow-up after liver transplantation. A
      multivariate analysis assessed factors associated with infections and mortality.
      RESULTS: Neither antifungal prophylaxis was associated with a fungal episode;
      however, group A patients experienced fewer bacterial infectious episodes (Mann
      Whitney U test P < .05). Furthermore, no renal impairment was observed in either
      groups. Nonetheless, patients undergoing fluconazole prophylaxis showed
      significant increases in immunosuppressive trough levels requiring dose
      adjustment. CONCLUSION: We observed comparable results of fluconazole and
      liposomal amphotericin B to prevent invasive fungal infections throughout 12
      months after surgery. The latter drug was associated with fewer bacterial
      infections after liver transplantation.

PMID- 22974887
TI  - Anidulafungin--a new therapeutic option for Candida infections in liver
      transplantation.
AB  - INTRODUCTION: In the last years, the incidence of Candida infections in liver
      transplant recipients has increased with still higher morbidity and mortality.
      Anidulafungin, a new echinocandin that does not interfere with cytochrome p450,
      shows no need for dosage adjustment based upon renal or hepatic function or
      weight. AIM: To analyze tolerance to and microbiologic and clinical efficacy of
      Anidulafungin to treat Candida infections in liver transplant patients. MATERIALS
      AND METHODS: This phase 3b, prospective, open-label, single-center study focused
      on liver transplant patients with a suspected and/or diagnosed Candida infection.
      The patients received Anidulafungin intravenously, optionally followed by oral
      therapy with azoles. The primary endpoint was the global response at the end of
      therapy; secondary endpoints were the efficacy of intravenous therapy, 90-day
      survival, as well as tolerance for and interaction with immunosuppresants.
      RESULTS: We considered 42 consecutive liver recipients transplanted between 2009
      and 2010 among whom 13 (31%) were recruited for the study and four patients were
      treated with Anidulafungin as empirical therapy, six as preemptive therapy, and
      three as targeted treatment for documented candidemia (7.1%). The
      immunosuppressive regimen consisted of tacrolimus and low dose of steroids. The
      Candida species were: C albicans (50%), C glabrata (12.5%), C parapsilosis
      (12.5%), C krusei (12.5%), C lusitaniae (6.2%), C tropicalis (6.2%), and multiple
      others (25%). The principle site of isolation was the bile (53.8%), followed by
      the bloodstream (23.1%), central venous catheters (15.4%), bronchoalveolar lavage
      (15.4%), peritoneum (7.7%), and other locations (7.7%). Two patients (15.4%) died
      of severe sepsis with multiple organ failure. There was no alteration of hepatic
      enzymes, indices of cholestasis or changes in immunosuppressant drug levels.
      CONCLUSION: Anidulafungin was an effective, safe, and well-tolerated drug. There
      were neither toxic effects to the grafts or adverse interactions with
      immunosuppresants.

PMID- 22974888
TI  - Telbivudin as prophylaxis for hepatitis B virus recurrence after liver
      transplantation: a case series in single-center experience.
AB  - BACKGROUND: Hepatitis B virus (HBV) recurrence after orthotopic liver
      transplantation (OLT) represents a severe condition that requires prophylaxis
      with specific immunoglobulin and lamivudine. Few studies have addressed the
      efficiency of other effective antiviral drugs posttransplantation or their impact
      on early renal function after transplantation. Herein, we have reported
      experience among seven transplanted patients prescribed Telbivudin (600 mg/d)
      while on the waiting list followed by treatment for 3 months after OLT. METHODS:
      Our series consisted of men with HBV-related end-stage liver disease. Once the
      patient started antiviral treatment, the viral load decreased rapidly while on
      the waiting list. All patients were evaluated for liver and renal functions
      immunosuppressive drug trough levels, CPK before (T0), as well as at 1 month
      (T1), and 3 months after liver transplant (T3). RESULTS: All patients received a
      CNI-based regimen. Their mean creatinine clearance (MDRD) was 72.5 mL/min at T0,
      69.2 mL/min at T1, and 71.0 mL/min at T3. Neither CPK or serum transaminase
      levels increased throughout the study. Once HBV-DNA was cleared while on the
      waiting list, it remained negative throughout the follow-up period. CONCLUSION:
      Telbivudin prophylaxis for HBV was safe and effective without any significant
      deleterious effect on liver or renal function tests after liver transplantation.

PMID- 22974889
TI  - Sorafenib for the treatment of recurrent hepatocellular carcinoma after liver
      transplantation?
AB  - BACKGROUND: There are scarce data on the use of sorafenib for the treatment of
      recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation
      (OLT). PATIENTS AND METHODS: Ten patients were treated with sorafenib after OLT
      following the Italian Drug Agency guidelines: they had well-compensated liver
      function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced
      stage HCC, good general condition (performance status 0), and not suitable for
      loco-regional therapies. Patients with HCC recurrence after OLT were treated with
      sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National
      Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with
      tumor responses evaluated acording to modified Response Evaluation Criteria in
      Select Tumors) criteria. RESULTS: Median duration of treatment was 10 months
      (range, 2-18). Seven patients (70%) received an additionally targeted therapy
      with mTOR inhibitors as part of their immunosuppressive regimen. Most common
      grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue
      (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4
      additional patients (40%) required a dose adjustment. No deterioration of liver
      graft function occurred. Three patients (30%) stopped treatment due to
      radiological progression of HCC, whereas 3 are still using the drug. Median time
      to progression was 8 months (range, 2-16). Median survival from start of therapy
      was 18 months (range, 4- 36). CONCLUSION: Our preliminary results suggest that
      sorafenib is a safe effective therapy for recurrent HCC after OLT.

PMID- 22974890
TI  - A single-center analysis to evaluate kidney function parameters after liver
      transplantation in adult patients.
AB  - Severe renal dysfunction may occur after orthotopic liver transplantation (OLT).
      In this study, we retrospectively analyzed a single-center series of adult liver
      recipients (n = 62) seeking to identify patients prone to develop renal
      dysfunction during follow-up. Liver recipients (age range, 53.54 +/- 8.19 years;
      female/male: 21/41) who underwent a first OLT from a brain dead donor were
      enrolled according to strict criteria. We enrolled only liver recipients with 5
      serum creatinine (SCr) measurements after hospital discharge and at least 1
      measurement/year with a follow-up period of not less than 2 years. We estimated
      glomerular filtration rate (eGFR) using the formula developed by the Mayo Clinic.
      The average rate of SCr change after OLT was 0.0065 +/- 0.013 mg/dL/mo. By
      calculating the per-patient slope, the average rate of SCr change was 0.000165 +/
      0.000383 mg/dL (0.000007 +/- 0.000017 mg/dL/mo). In regression models evaluated
      with SCr as the dependent variable versus post-OLT time, no significance was
      observed (P = .130). The average rate of eGFR change after OLT was -0.462 +/-
      0.883 mL/min/mo. By calculating the per-patient slope, the average rate of eGFR
      change was -0.009 +/- 0.0026 mL/min (-0.0004 +/- 0.0012 mL/min/mo). In the
      regression models evaluated with eGFR as dependent variable versus post-OLT time,
      no significance occurred (P = .168). By applying the regression prediction to SCr
      at 3 to 5 versus the 1 to 2 post-OLT measurements, we noted 3 male liver
      recipients (MLR) whose SCr values were significantly higher than the predicted
      values: MLR1: P = .048 at measurement 4; MLR2: P = .019 at measurement 4; and
      MLR3: P = .017 at measurement 5. Conversely, we did not observed a significant
      difference between observed versus predicted eGFR values. Clinical decisions on
      immunosuppressive treatments for liver recipients should be determined also on
      the basis of the series of post-OLT kidney function, which should be studied with
      rigorous evaluation of fitted regression models.

PMID- 22974891
TI  - Postoperative troponin T elevation as a predictor of early acute kidney injury
      after orthotopic liver transplantation: a preliminary retrospective study.
AB  - BACKGROUND: Slight alterations in cardiac enzymes are frequently observed
      perioperatively among liver transplant patients. The significance of these
      changes in the absence of ongoing acute cardiac pathology is unknown. We sought
      to evaluate the link between early postoperative anomalies of serum cardiac
      troponin T (cTnT) in the absence of an evident cardiac cause and kidney injury
      during the first week of hospital stay. METHODS: We retrospectively enrolled 30
      patients in the study, recording several perioperative variables, particularly
      cTnT on intensive care unit ICU arrival as well as 6 and 12 hours later. We
      grouped patients with cTnT levels >0.03 ng/mL as the high-TnT group; the others
      were control subjects. We recorded the highest serum creatinine, aspartate
      aminotransferase, alanine aminotransferase, and bilirubin levels during the first
      week of the hospital stay. Glomerular filtration rate (GFR) was calculated
      according to the Cockroft-Gault formula. RESULTS: Ten patients composed the high
      TnT group. Their perioperative variables showed higher Model for End-Stage Liver
      Disease (MELD) scores and significantly greater incidences of acute kidney
      injury, failure, and dialysis need than control patients. GFR dropped from 118 to
      66 mL/min among this group versus 112 to 105 mL/min in control subjects (P =
      .021). Binary logistic regression analysis revealed a higher association between
      the high-TnT group and acute kidney injury (P = .036) than with the MELD score (P
      = .719). CONCLUSIONS: Serum cTnT levels could be influenced by both preoperative
      and intraoperative conditions that predispose to kidney injury.

PMID- 22974892
TI  - Factors predicting ischemic-type biliary lesions (ITBLs) after liver
      transplantation.
AB  - Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major
      cause of morbidity in liver transplant recipients, significantly affecting the
      chance of survival of both patients and grafts. We retrospectively reviewed 10
      years of prospectively collected donor and recipient data from April 2001 to
      April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible
      predisposing factors, including donor and recipient data. Two hundred fifty-one
      grafts were harvested: 222 of them were transplanted at our institution, the
      remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular
      steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold
      ischemia time (P = .048) significantly increased the risk of ITBL, also as an
      independent risk factor after multivariate analysis.

PMID- 22974893
TI  - Metabolic syndrome and cardiovascular risk after liver transplantation: a single
      center experience.
AB  - Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently
      observed among orthotopic liver transplantation (OLT) patients. These
      alterations, which are probably multifactorial in origin, contribute to
      posttransplantation metabolic syndrome (PTMS), which increases the risk of
      cardiovascular events. We assessed the prevalence of PTMS (diagnosed according to
      modified NCEP Adult Treatment Panel III criteria) in 156 OLT patients undergoing
      regular follow-up after transplantation (median 68 months; range, 6 to 234
      months). Several pre- and post-OLT data were collected to identify the factors
      associated with the presence of PTMS which was found in 28% of cases. The only
      independent predictive factors for PTMS were diabetes mellitus and patients who
      were overweight or obese before-OLT. The prevalence of PTSM was lower among
      patients on tacrolimus immunosuppression. In our population, 21% of patients
      showed a high cardiovascular risk score with a 4% incidence of cardiovascular
      events, which was higher among subjects with PTMS. Close follow-up is mandatory
      to prevent the development of PTMS mainly among overweight and diabetic patients
      before transplantation.

PMID- 22974894
TI  - Ventricular assist devices as a bridge to heart transplantation or as destination
      therapy in pediatric patients.
AB  - PURPOSE: Despite the remarkable advances with the use of ventricular assist
      devices (VAD) in adults, pneumatic pulsatile support in children is still
      limited. We report on our experience in the pediatric population. METHODS:
      Retrospective review of 27 consecutive children offered mechanical support with
      Berlin Heart as a bridge to heart transplant, and Jarvik 2000 as a destination
      therapy from February 2002 to October 2011. RESULTS: The median patient age was
      4.8 years (range = 75 days to 20.5 years). The median patient weight was 18.6 kg
      (range = 2.9-63 kg). We divided the patients in two groups, including in group I
      patients assisted for bridging to heart transplantation and in group II patients
      with Duchenne's dystrophy assisted as destination therapy. In the group I, 11
      patients required biventricular mechanical support (BVAD), but in all other
      cases, a single left VAD proved sufficient (56%). The median duration of VAD
      support was 48 days (1 to 192 days). The median pre-VAD pulmonary vascular
      resistance index (Rpi) was 5.7 WU/m(2) (3.5 to 14.4 WU/m(2)). Twelve patients
      (48%) were successfully bridged to heart transplantation after a median duration
      of mechanical support of 63 days (range = 2-168 days). Ten deaths occurred (40%),
      three for neurological complications, two for sepsis, two for multiorgan failure,
      and three other for device malfunctioning. Since 2007, the survival rate of our
      patients has increased from 33% to 75%, and the need for BVAD has decreased from
      89% to 23%. In the group II, two patients with mean age of 15.3 years were
      assisted with Jarvik 2000, and both of them are alive in a follow-up of 10.4
      months. In two patients with Rpi > 10 WU/m(2), unresponsive to pulmonary
      vasodilatator therapy, Rpi dropped to 2.2 and 2 WU/m(2) after 40 and 23 days of
      BVAD support, respectively. Six patients (32%) required at least one pump change.
      Of 12 patients undergoing heart transplantation, five developed an extremely
      elevated (>60%) panel-reactive antibody by enzyme-linked immunosorbent assay,
      confirmed by Luminex. All of them experienced at least one acute episode of
      rejection in the first month after heart transplant, needing plasmapheresis. The
      survival rate after heart transplantation was 100% with a median follow-up of
      34.4 months (45 days to 8.7 years). CONCLUSIONS: Mechanical support in children
      with end-stage heart failure is an effective strategy as a bridge to heart
      transplantation with a reasonable morbidity and mortality. BVAD support may offer
      an additional means to reverse extremely elevated pulmonary vascular resistance.
      The total implantable system opens a future scenarios for patients not eligible
      for heart transplantation.

PMID- 22974895
TI  - Right ventricular longitudinal strain and right ventricular stroke work index in
      patients with severe heart failure: left ventricular assist device suitability
      for transplant candidates.
AB  - BACKGROUND: Right ventricular (RV) systolic function has a critical role in
      determining the clinical outcome and the success of using left ventricular assist
      devices in patients with refractory heart failure. RV deformation analysis by
      speckle tracking echocardiography (STE) has recently allowed the analysis of RV
      longitudinal function. Using cardiac catheterization as the reference standard,
      this study aimed to explore the correlation between RV longitudinal function by
      STE and RV stroke work index (RVSWI) among patients referred for cardiac
      transplantation. METHODS: Right heart catheterization and transthoracic echo
      Doppler were simultaneously performed in 47 patients referred for cardiac
      transplant assessment due to refractory heart failure (ejection fraction 25.1 +/-
      4.5%). Thermodilution RV stroke volume and invasive pulmonary pressures were used
      to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging RV
      free-wall segments (free-wall RVLS). We also calculated. Tricuspid S' and
      tricuspid annular plane systolic excursion (TAPSE). RESULTS: No significant
      correlation was observed for TAPSE on tricuspid S' with RV stroke volume (r =
      0.14 and r = 0.06, respectively). A close negative correlation between free-wall
      RVLS and RVSWI was found (r = -0.82; P < .0001). Furthermore, free-wall RVLS
      showed the highest diagnostic accuracy (area under the curve of 0.90) with good
      sensitivity and specificity of 95% and 91%, respectively, to predict depressed
      RVSWI using a cutoff value less than -11.8%. CONCLUSIONS: Among patients referred
      for heart transplantation, TAPSE and tricuspid S' did not correlate with
      invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated
      with RVSWI, providing a better estimate of RV systolic performance.

PMID- 22974896
TI  - Noninvasive high-frequency percussive ventilation in the prone position after
      lung transplantation.
AB  - Noninvasive positive-pressure ventilation (NIV), which represents a consolidated
      treatment of both acute and chronic respiratory failure, is increasingly being
      used to maintain spontaneous ventilation in lung transplant patients with
      impending pulmonary complications. Adding a noninvasive inspiratory support plus
      positive end-expiratory pressure (PEEP) has proven to be useful in preventing
      endotracheal mechanical ventilation, airway injury, and infections. Lung
      recipients with closure of the small airways in the dependent regions may also
      benefit from the prone position, which is helpful to promote recruitment of
      nonaerated alveoli and faster healing of consolidated atelectatic areas. In
      patients with localized or diffuse lung infiltrates, high-frequency percussive
      ventilation (HFPV), by either an invasive airway or a facial mask, has been
      adopted as an alternative ventilatory mode to enhance airway opening, limit
      potential respirator-associated lung injury, and improve mucus clearance. In
      nonintubated lung recipients at risk for volubarotrauma with conventional
      mechanical ventilation, it allows oxygen diffusion into the distal airways at
      lower mean airway pressures while avoiding repetitive cyclical opening and
      closing of the terminal airways. We summarize the clinical course of 3 patients
      with post-lung transplantation respiratory complications who were noninvasively
      ventilated with HFPV in the prone position. Major advantages of this treatment
      included gradual improvement of spontaneous clearance of bronchial secretions,
      significant attenuation of graft infiltrates and consolidations, a reduction in
      the number of bronchoscopies required, a decrease in spontaneous respiratory rate
      and work of breathing, and a significant improvement in gas exchange. The
      patients found HFPV with either standard facial mask or total mask interface to
      be comfortable or only mildly uncomfortable, and after the sessions they felt
      more restored. HFPV by facial mask in the prone position may be an interesting
      and attractive alternative to standard NIV, one that is more useful when
      implemented before full-blown respiratory failure is established.

PMID- 22974897
TI  - Lung transplantation and posterior reversible encephalopathy syndrome: a case
      series.
AB  - Posterior reversible encephalopathy syndrome is a neurological problem
      characterized by headache, altered mental status, focal neurological deficits,
      visual disorders, and seizures. The disorder is related to a number of diseases
      including calcineurin inhibitor therapy in solid organ transplantation. The
      incidence of posterior reversible encephalopathy syndrome in lung transplantation
      patients is unclear; probably the majority of the cases are unreported. The
      authors have described a case series constituted of four patients presenting
      posterior reversible encephalopathy syndrome after bilateral lung
      transplantation. The cases had in common complicated surgery and a posttransplant
      course characterized by hypertension, hypomagnesemia and acidosis. Invasive
      mechanical ventilation, calcineurin inhibitor discontinuation, aggressive
      antihypertensive therapy, and electrolyte regulation led to near complete
      recovery of symptoms.

PMID- 22974898
TI  - Subnormothermic machine perfusion for non-heart-beating donor liver grafts
      preservation in a Swine model: a new strategy to increase the donor pool?
AB  - We previously reported that subnormothermic machine perfusion (sMP; 20 degrees C)
      is able to improve the preservation of livers obtained from non-heart-beating
      donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to
      preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers
      were perfused for 6 hours with Celsior at 20 degrees C. In the CS group they were
      stored in Celsior at 4 degrees C for 6 hours as usual. To simulate liver
      transplantation, both sMP- and CS-preserved livers were reperfused using a
      mechanical continuous perfusion system with autologus blood for 2 hours at 37
      degrees C. At 120 min after reperfusion aspartate aminotransferase levels in sMP
      versus CS were 499 +/- 198 versus 7648 +/- 2806 U/L (P < .01); lactate
      dehydrogenase 1685 +/- 418 versus 12998 +/- 3039 U/L (P < .01); and lactic acid
      4.78 +/- 3.02 versus 10.46 +/- 1.79 mmol/L (P < .01) respectively. The sMP group
      showed better histopathologic results with significantly less hepatic damage.
      This study confirmed that sMP was able to resuscitate liver grafts from large
      NHBD animals.

PMID- 22974899
TI  - Development of a standardized model for liver failure in pigs:
      anatomopathophysiologic findings after extended liver resection.
AB  - Eighteen pigs weighing a mean 19 +/- 4 kg, were divided into group 1 (n = 2),
      that underwent resection of the left lateral lobe, group 2 (n = 2), resection of
      the left median and right median lobes; and group 3 (n = 18), resection of the
      left lateral, left median, right median, and right lateral lobes. All animals
      were followed for 5 days. Liver failure (n = 8) leading to animal death within 3
      days after surgery was observed in 65% of group 3, whereas no group 1 or 2 animal
      experienced liver insufficiency. Multivariate analysis revealed that the extent
      of liver resection expressed as a percentage of total body weight <2.3%,
      international normalized ratio > 1.6 as postoperative day 2, serum bilirubin >
      4.2 on postoperative day 2, and serum lactates > 9 mmol/L after resection were
      independent predictors of liver failure (P < .05). The number of resected liver
      lobes was not a good predictor of liver failure in swine, whereas the extent of
      resection expressed as a percentage of total body weight was an independent
      predictor of early liver failure. A resected liver-to-body weight ratio >2.3% was
      associated with a 65% probability of developing liver insufficiency. This
      parameter may be useful when developing a model of liver failure after extended
      liver resection in swine.

PMID- 22974900
TI  - Management of kidney transplantation in a factor VII-deficient patient: case
      report.
AB  - Transplantation in patients with congenital bleeding disorders is a challenge
      requiring an integrated approach of various specialists. Renal transplantation,
      the most frequent type of solid organ transplantation, is rarely performed in
      individuals with congenital hemorrhagic disorders. We performed a renal
      transplantation in a 53-year-old man with end-stage renal disease and congenital
      coagulation factor VII deficiency, a rare bleeding disorder with a peculiar
      clinical picture requiring replacement therapy in surgical interventions.
      Perioperative bleeding was successfully prevented by administration of
      recombinant activated factor VII. Treatment schedule, administration rate, and
      long-term follow-up are reported in detail. Our report confirmed the feasibility
      and safety of recombinant activated factor VII in major surgical procedures like
      solid organ transplantations. Success requires evaluation of doses and
      therapeutic schedules as well as a multidisciplinary approach.

PMID- 22974901
TI  - Laparoscopic approach for an intra-abdominal kidney allograft nephrectomy after
      pediatric transplantation: a case report.
AB  - We report a case of minimally invasive nephrectomy of a kidney transplanted into
      the abdominal cavity in a child. A 15-year-old girl underwent transplantation
      with a cadaveric donor kidney due to congenital pyelonephritis, vesicoureteral
      reflux, and secondary bladder atrophy. The transplant was complicated by
      hyperacute rejection, cytomegalovirus infection, and anastomotic stenosis of the
      Bricker neobladder. After recurrent urinary tract infections, the patient was
      reintroduced to hemodialysis in 2010. After pneumo-peritoneum, we placed 2 10-mm
      trocars in the hypochondrium and left side and 2 5-mm in the left iliac fossa and
      right upper quadrant. The transplanted kidney was skeletonized, the artery and
      vein were cut to the end-to-side anastomoses to the juxta-renal aorta and cava
      using an automatic 35-mm, stapler, and the ureter was dissected and closed with
      clips. Via a Pfannestiel minilaparotomy we extracted the allograft. The patient
      was discharged on the third postoperative day. After 4 months of follow-up, she
      is alive an on dialysis. Laparoscopic nephrectomy of a kidney transplanted into
      the abdominal cavity is feasible and safe in centers with skilled minimally
      invasive techniques.

PMID- 22974902
TI  - Liver transplantation for massive hepatomegaly due to polycystic liver disease:
      an extreme case.
AB  - BACKGROUND: Polycystic liver disease (PLD) is due to a genetic disorder and
      frequently coexists with polycystic kidney disease (PKD). If the cysts produce
      symptomatology owing to their number and size, many palliative treatments are
      available. When none of the liver parenchyma is spared, or kidney insufficiency
      is marked, the only potentially curable treatment is liver transplantation (LT).
      CASE REPORT: A 49-year old woman, diagnosed with PLD and PKD, was listed in
      January 2008 for combined LT and kidney transplantation (KT). A compatible organ
      became available 8 months later. Despite preserved liver function, the patient's
      clinical condition was poor; she experienced dyspnea, advanced anorexia,
      abdominal pain, and severe ascites. At LT, which took 9 hours and was performed
      using the classic technique, the liver was hard, massive in size (15.5 kg), and
      not dissociable from the vena cava. The postoperative course was complicated by
      many septic episodes, the last one being fatal for the patient at 4 months after
      transplantation. DISCUSSION: LT for PLD in many series shows a high mortality
      rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients
      properly, because liver function is usually preserved. The liver can achieve a
      massive size causing many symptoms, especially malnutrition and ascites; in this
      setting LT is the only possible treatment. Patients with a low MELD score undergo
      LT with severe malnutrition that predisposes them to greater susceptibility to
      sepsis. To identify predictor factors, beyond MELD criteria that relate to the
      increased liver volume before development of late symptoms is essential to
      expeditiously treat patients with the poorest prognosis to improve their
      outcomes.

PMID- 22974903
TI  - Early lung retransplantation in a patient affected by cystic fibrosis correlated
      with donor cause of death: a case report.
AB  - The relationship between donor cause of death and lung transplantation outcomes
      remains unclear. We report a case of lung transplantation in a young patient
      affected by cystic fibrosis. Immediately after lung reperfusion a pulmonary
      hypertension was observed that was intractable with maximal medical therapy
      requiring surgical resection of the left lower lobe which became congested after
      a few days. The donor had died from suicidal hanging; the authors attributed the
      posttransplantation pulmonary hypertension which is an uncommon form of primary
      graft dysfunction to this cause of death. The patient was treated with early
      bilateral lung retransplantation which required a long, troublesome hospital
      stay. In conclusion, the authors warn against the use of lungs from donors who
      die due to hanging even when the gas exchanges were ideal.

PMID- 22974905
TI  - Development of a non-heart-beating donor program and results after the first
      year.
AB  - Our lung transplant unit began activity in October 2008. We have performed 37
      lung transplants with a hospital mortality of 2.7% (n = 1). The need for a
      greater number of donors and the presence of an already existent non-heart
      beating donor (NHBD) program for abdominal grafts and tissues encouraged us to
      consider assessing lung grafts from these donors. It was necessary to develop a
      new multiorgan preservation methodology, "bithermia preservation." The clinical
      experience with which during the first year June 2010 to July 2011, including 15
      NHBDs is presented herein. The chest x-ray was normal in 6 donors (40%) and 7 had
      pulmonary infiltrates. Bronchoscopy was normal in 8 donors (53%) but 3 had
      abundant bleeding airway secretions and signs of bronchoaspiration. Preservation
      procedures were performed in 6 donors. Pulmonary functional evaluation in 4
      donors showed gas measurements to be adequate in 75% of cases. Three double-lung
      grafts were judged to be valid for implantation, among which we performed 3 lung
      transplantations, 1 bilateral and 2 unilaterals, while 2 grafts were offered to
      the National Transplant Organization for other units. No transplant suffered
      primary graft dysfunction; all 3 showed excellent function allowing early
      extubation in 2 cases. There was no in-hospital mortality. All 3 patients are
      alive and leading normal lives; none has bronchiolitis obliterans syndrome. In
      conclusion, the "bithermia preservation" methodology achieved adequate lung
      preservation in NHBDs, allowing liver, kidneys, and lungs to be obtained from the
      same donor.

PMID- 22974906
TI  - Clinical variables and neuromonitoring information (intracranial pressure and
      brain tissue oxygenation) as predictors of brain-death development after severe
      traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to ascertain the role of
      clinical variables and neuromonitoring data as predictors of brain death (BD)
      after severe traumatic brain injury (TBI). PATIENTS AND METHODS: This prospective
      observational study involved severe TBI patients admitted to the intensive care
      unit between October 2009 and May 2011. The following variables were recorded:
      gender, age, reference Glasgow Coma Scale after resuscitation, pupillary
      reactivity, prehospital hypotension and desaturation, injury severity score,
      computed tomography (CT) findings, intracranial hypertension, and low brain
      tissue oxygenation (Pti02) levels (<16 mm Hg), as well as the final result of BD.
      RESULTS: Among 61 patients (86.9% males) who met the inclusion criteria, the
      average age was 37.69 +/- 16.44 years. Traffic accidents were the main cause of
      TBI (62.3%). The patients at risk of progressing to BD (14.8% of the entire
      cohort) were those with a mass lesion on CT (odds ratio [OR] 33.6; 95% confidence
      interval [CI]: 3.75-300.30; P = .002), altered pupillary reaction at admission
      (OR 25.5; 95% CI: 2.27-285.65; P = .009), as well low Pti02 levels on admission
      (OR 20.41; 95% CI: 3.52-118.33; P < .001) and during the first 24 hours of
      neuromonitoring (OR 20; 95% CI: 2.90-137.83; P < .001). Multivariate logistic
      regression showed that a low Pti02 level on admission was the best independent
      predictor for BD (OR 20.41; 95% CI: 3.53-118.33; P = .001). CONCLUSIONS: Clinical
      variables and neuromonitoring information may identify TBI patients at risk of
      deterioration to BD.

PMID- 22974907
TI  - Renal replacement therapy in patients with HIV infection in a European region:
      outcomes following renal transplantation.
AB  - INTRODUCTION: The prognosis of HIV infection has improved dramatically in
      patients with end-stage renal disease (ESRD). Thus, HIV infection is no longer an
      absolute contraindication for renal transplantation. METHODS: A cross-sectional
      study was performed to analyze the characteristics of HIV patients receiving
      renal replacement therapy (RRT) in September 2011, using data from the Registry
      of Renal Patients in Andalusia. A retrospective cohort study was also carried
      out, analyzing patients receiving kidney transplants in the era of highly active
      antiretroviral therapy. RESULTS: In Andalusia in September 2011, 8744 patients
      were on RRT; of these, 48 had HIV infection (prevalence 0.54%). The RRT modality
      was very different between HIV-negative and HIV-positive patients: renal
      transplantation 49.2% and 16.7%, hemodialysis 46.8% and 81.3%, and peritoneal
      dialysis 4% and 2%, respectively. The most frequent ESRD etiology was
      glomerulonephritis (37.5%). Twenty-seven (56.3%) had hepatitis C coinfection.
      Only three patients (7.5%) were on the waiting list for renal transplantation.
      From 2001 to September 2011, 10 HIV-infected patients received a renal
      transplantation (median follow-up 40.5 months). The initial immunosuppressive
      treatment included tacrolimus and mycophenolate without induction therapy. Only
      two patients presented acute rejection, both borderline and corticosensitive. All
      remain alive and the graft survival was 100% in the first and third years
      posttransplant. We compared demographic and comorbidity variables between
      patients transplanted or included on the waiting list (n = 12) and patients
      excluded and never transplanted (n = 36). We found differences only in the ESRD
      etiology (higher incidence of glomerulonephritis in excluded patients).
      CONCLUSIONS: Renal transplantation is safe in correctly selected HIV-infected
      patients. The number of patients on the waiting list is very small. This may
      reflect the high comorbidity but it is also possible that these patients are
      still not being assessed systematically for transplant in all centers.

PMID- 22974908
TI  - Pairs of kidneys transplanted from the same donor: is there any difference?
AB  - OBJECTIVES: The aim of this study was to compare the evolution of the first
      kidney in relation to the second kidney transplanted from the same donor,
      focusing on the impact that a longer cold ischemia time may have as an
      independent variable. MATERIAL AND METHODS: The study included 44 pairs of
      kidneys transplanted from the same donor between February 2008 and October 2010,
      divided into Groups 1 and 2 according to the graft placement order. The variables
      analyzed were age, sex, comorbidities, number of transfusions, length of hospital
      stay, maximum peak PRA, immunologic incompatibility, ischemia time, delayed graft
      function (DGF), presence of rejection, creatinine clearance at first week, at 3
      months and at 1 year, and vascular and tract complications in each group.
      RESULTS: The mean cold ischemia time was 15.6 hours in Group 1 and 20.1 hours in
      Group 2 (P < .001). The average recipient age was 52.79 years in Group 1 and
      54.52 years in Group 2, with an equal sex ratio in the two groups; an average of
      2.06 PRC were transfused prior to transplantation in Group 1 and 0.93 PRC in
      Group 2; the average length of stay was similar in the two groups. Major DR
      incompatibility was only found in Group 2 (P < .03). Creatinine clearance at
      first week, DGF and acute rejection showed worse results in Group 2, but these
      differences were not significant. Vascular complications were present in 4.5% and
      2.3% of Groups 1 and 2, respectively, and tract complications were 6.8% and
      11.4%. CONCLUSIONS: A greater tendency to DGF, early rejection and tract
      complications were found in the group with longer ischemia time, although the
      difference was not statistically significant. Larger series will be necessary to
      confirm our results.

PMID- 22974909
TI  - Optimization of expanded donors using dual kidney transplantation: case-control
      study.
AB  - BACKGROUND: Cadaveric donation is now experiencing a trend toward the use of
      expanded criteria donors (ECD) who may not yield a suitable kidney for single
      organ transplantation which has occasionally led to their use as dual renal
      transplantations. MATERIAL AND METHODS: We undertook a case-control study to
      analyze our experiences between May 2007 and March 2011 with 80 kidneys from ECD
      who were older than 65 years. Of these, 40 were used as single transplants (STX)
      and the other 40 as dual cases (DTX). Criteria to determine STX versus DTX were
      established by biopsy results and other donor factors. RESULTS: The mean age of
      the ECD for STX was 68.7 +/- 3.0 years and for DTX, 74.2 +/- 4.3 years (P <
      .001), with more women among DTX (75%) versus STX (40%; P < .001). The DTX
      kidneys showed higher biopsy scores than the STX organs. DTX were older than STX
      recipients, but there were no differences in cold ischemia time, delayed graft
      function, hemorrhagic complications or reinterventions. DTX recipients achieved
      better CrCl at 1, 3, 6, and 12 months, although only significantly so at 6 months
      (53.4 +/- 19.5 Ml/min versus 44.5 +/- 15.6 mL/min; P < .05). Death-censored graft
      survival was 90% at 3 years for both groups. CONCLUSIONS: DTX offered good
      results for graft survival and renal function, despite the more complicated
      surgery and worse quality of the allografts. DTX allowed the use of ECD kidneys
      that showed less satisfactory histologic and donor characteristics.

PMID- 22974910
TI  - Evolution of left ventricular mass in renal transplant recipients: the influence
      of glucose homeostasis and oxidative stress.
AB  - BACKGROUND: Left ventricular hypertrophy, considered an independent factor for
      cardiovascular mortality, is frequent among renal transplant recipients (RTR), in
      whom we investigated changes in left ventricular mass (LVM) after grafting and
      associations with possible causal factors, especially glucose metabolism and
      oxidative stress. METHODS: We performed a prospective study of 37 RTR without
      prior diabetes mellitus who were evaluated at three times after transplantation
      (medians of 0.6, 16 and 28 months) by means of the LVM index (LVMI,
      echocardiographic measure of LVM related to body surface area, g/m(2)), oral
      glucose tolerance test and determinations of malondialdehyde and total
      glutathione (GSH), as well as glomerular filtration rate (GFR) estimate by the
      Modification of Diet in Renal Disease formula. We calculated the overall
      increment (DeltaLVMI) and percent change of LVMI. Patients were diagnosed to be
      prediabetic (PD) or new-onset diabetes after transplant (NODAT) according to ADA
      criteria. RESULTS: The mean LVMI decreased significantly over time among whole
      group baseline = 108.34 +/- 27.71 g/m(2) versus middle: 100.03 +/- 27.53 g/m(2)
      versus final: 90.62 +/- 24.06 g/m(2) (P = .000). However, 13.5% of subjects
      showed an increased LVMI and 59.5%, a decrease less than 20%. Patients with NODAT
      at the end of the study showed a positive DeltaLVMI, which was negative in
      nondiabetics (0.24 +/- 16.14 versus -19.86 +/- 12.61 g/m(2), P = .018). Compared
      with DeltaLVMI(-) recipients, patients with DeltaLVMI(+) showed a greater
      proportion of PD and NODAT at baseline (60% and 40% versus 18.8% and 12.5%, P =
      .017), and significantly higher all-time fasting glycemia, lower estimated GFR,
      and greater increments of malondialdehyde and GSH over time. Those with a <20%
      LVMI decrease experienced progressive GFR impairment over time, as opposed to
      those with an LVMI decrease > 20%, who showed greater and improving GFR over the
      whole study. CONCLUSIONS: LVMI does not always improve in RTR; the evolution of
      ventricular mass after renal transplantation is influenced by glucose metabolism
      disorders, oxidative stress, and graft function.

PMID- 22974911
TI  - Survival of lupus nephritis patients after renal transplantation in Malaga.
AB  - BACKGROUND: Studies have shown that the survival of patients with lupus nephritis
      (LN) who receive a transplant has results similar to those of nondiabetic control
      subjects. OBJECTIVE: The aim of this study was to evaluate the survival of lupus
      patients who received a transplant at our center, and to determine risk factors
      for mortality and graft loss. METHODS: This case-control (1:2) study comprised
      patients with chronic kidney disease secondary to LN who received a kidney
      transplant (n = 32) in the Malaga area from 1985 to 2010. The controls subjects
      (n = 64) were matched by age, sex, and transplant period. We analyzed graft and
      patient survivals and risk factors compared with long-term transplant patients
      without LN. RESULTS: No differences were found in the variables analyzed between
      groups, except for the most frequent cause of donor death, which was almost
      significant: stroke in LN and traumatic brain injury in control subjects (P =
      .05). of the whole study sample, 45% lost the graft, primarily owing to chronic
      kidney disease (53.5%), followed by vascular thrombosis (16.3%); P = .57.
      Censored graft losses occurred in 63% of the patients transplanted before 2000,
      whereas it occurred in 20% of those transplanted after 2000 (P < .001). Censored
      graft survival was similar between the groups throughout the followup, as was
      patient survival. Cox regression showed that only acute rejection was associated
      with a 2-fold increased risk of graft loss. CONCLUSIONS: Our lupus transplant
      population showed no differences in graft or patient survival compared with
      control subjects. Those patients who received a transplant from 2000 had better
      results, which may be related to several factors, such as immunosuppression,
      correction of cardiovascular conditions, or other factors. Risk factors for death
      and graft loss were similar to the control population.

PMID- 22974912
TI  - Impact of the model for end-stage liver disease score on mortality after liver
      transplantation.
AB  - OBJECTIVE: The objective of this study was to analyze survival, and mortality,
      rates as well as its causes during the month following liver transplantation with
      respect to the model for end-stage liver disease (MELD) model. MATERIAL AND
      METHODS: We reviewed the mortality at 24 and 48 hours as well as 1 and 4 weeks of
      380 transplanted patients over the past 7 years with regard to the MELD score.
      RESULTS: The mean patient age was 55 years. Among subjects with MELD score <= 15
      (n = 142; 37.36%), there were 34 deaths (23.94%), including 7 (4.92%) who died
      during the first month. The mean cause of death during this period was hemorrhage
      (n = 3; 8.8%). Among those with MELD scores between 16 and 18 (n = 76; 20%), the
      mortality rate increased to 23.68% (n = 18), including 3 who died during the
      first month (3.94%) with 1 case due to hemorrhage. Among the cohort with MELD
      scores between 19 and 21 (n = 78; 20.52%), 25 (32.05%) died, including 9 during
      the first month (11.53%). The most frequent cause of death was septic shock (n =
      5; 20%). The mortality rate among patients with a MELD score between 22 and 24
      was 22% (n = 11), of which 8% (n = 4) died in the month. The mean cause of death
      during this period was multiple organ dysfunction (n = 2; 18.1%). The patient
      group with a MELD score >24 had a 32.3% mortality rate (n = 11); 4 patients died
      during the first month following transplantation (11.76%). The most frequent
      cause of death was hemorrhage (n = 2; 18.1%). CONCLUSIONS: Survival during the
      first month did not seem to be related to the MELD score at the time of
      transplantation, nor did we observe a direct correlation between the MELD score
      and the overall risk of mortality.

PMID- 22974913
TI  - Perioperative values of glutathione peroxidase activity and malondialdehyde
      levels in enolic cirrhotic recipients of a liver transplant.
AB  - Reactive oxygen species play a central role in ischemia-reperfusion injury after
      organ transplantation. They are degraded by endogenous radical scavengers such as
      antioxidant enzymes. The purpose of this study was to evaluate the temporal
      variation in glutathione peroxidase (GPX) activity and malondialdehyde (MDA)
      levels among alcoholic cirrhotic recipients of liver transplantations. The study
      included 30 recipients: 26 males and 4 females in the provided blood samples
      before and after transplantation. The results showed significant enhancement of
      MDA levels at 1 and 6 hours after transplantation: 4.458 +/- 2.273 MUmol/L and
      4.4628 +/- 2.405 MUmol/L respectively (P < .001). In contrast, GPX activity
      showed a maximum at 3 days there after 3.541 +/- 2,315 nmol/mg protein. In
      conclusion, although MDA levels show an enormous increase at 1 hour after
      transplantation suggesting lipid peroxidation, they were compensated by GPX
      activity thereafter, indicating control of the oxidative stress generated by
      liver transplantation.

PMID- 22974914
TI  - Echocardiographic study in cirrhotic patient candidates for liver
      transplantation.
AB  - We studied 81 cirrhotic patients who were candidates for liver transplantation to
      evaluate frequently detected cardiac alterations by echocardiographic study.
      Patients were distributed into three groups: group 1 comprised alcoholic
      cirrhotic patients (n = 40); group 2, viral cirrhotic patients (hepatitis C or B
      virus) (n = 35); and group 3, patients with primary biliary cirrhosis (n = 6).
      Cardiac chambers and diastolic functions were estimated by two-dimensional
      transthoracic echocardiography in M mode and Doppler. The most frequently
      detected cardiac structural alterations were left atrial diameter enlargement in
      100% of the women and 40% of the men in group 1; 87.5% of the women and 15.4% of
      the men in group 2; and 33.3% of the women in group 3. Interventricular wall
      thickness enlargement in 50% of the women and 27.8% of the men in group 1, 25% of
      the women and 30.8% of the men in group 2, and 16.4% of the women in group 3. The
      prevalence of diastolic dysfunction was 45% in group 1, 32.3% in group 2, and
      16.4% in group 3 (P > .05). There were no significant differences between the
      groups in cardiac chamber dimensions, left ventricular wall thickness, or
      prevalence of diastolic dysfunction.

PMID- 22974915
TI  - Liver transplantation due to fulminant hepatic failure.
AB  - OBJECTIVES: To analyze the epidemiology, causes, complications, and mortality of
      liver transplants following fulminant hepatic failure over the last 16 years.
      MATERIALS AND METHODS: We completed a descriptive analysis of 21 patients with
      fulminant hepatic failure and a liver transplant. In almost half of the cases,
      the origin of liver failure was unknown. RESULTS: The mean age was 36 years; the
      study group was 47.61% female (n = 10) and 52.39% male (n = 11). The most common
      early complication was transplant rejection, which occurred in 33.3% of all
      patients (n = 7) and was confirmed by liver biopsy; the most frequent long-term
      complication was autoimmune hepatitis. Two retransplantations were necessary. The
      total mortality rate was 38.1% (n = 8) with late mortality in three patients
      (14.3%). CONCLUSIONS: Orthotopic liver transplantation as a treatment for
      fulminant hepatitis has a higher mortality rate than orthotopic liver
      transplantation due to other causes. It does, however, enable the survival of 62%
      of the patients who otherwise would have died due to liver failure. The etiology
      of most of the cases was unknown. We should point out the high incidence rates
      for transplant rejection and late autoimmune hepatitis, in addition to the
      possibility of hemorrhagic colonic diseases that may be associated with the
      condition causing liver failure. Multidisciplinary control over the patient is
      useful for deciding at which time a liver transplant would become the only
      treatment option.

PMID- 22974916
TI  - Intraoperative hepatic artery blood flow predicts early hepatic artery thrombosis
      after liver transplantation.
AB  - Hepatic artery complications after orthotopic liver transplantation are
      associated with a high rate of graft loss and mortality (23% to 35%) because they
      can lead to liver ischemia. The reported incidence of hepatic artery thrombosis
      (HAT) after adult liver transplantation is 2.5% to 6.8%. Typically, these
      patients are treated with urgent surgical revascularization or emergent liver
      retransplantation. Since January 2007, we have recorded the postanastomotic
      hepatic artery flow after revascularization. The aim of this study was to assess
      the relationship between hepatic blood flow on revascularization and early HAT.
      Retrospectively, we reviewed perioperative variables from 110 consecutive liver
      transplantation performed at the Virgen del Rocio University Hospital (Seville,
      Spain) between January 2007 and October 2010. We evaluated the following
      preoperative (donor and recipient) and intraoperative variables: donor and
      recipient age, cytomegalovirus serology, ABO-compatibility, anatomical variations
      of the donor hepatic artery, number of arterial anastomoses, portal and hepatic
      artery flow before closure, cold ischemia time, and blood transfusion. These
      variables were included in a univariate analysis. Of the 110 patients included in
      the study, 85 (77.7%) were male. The median age was 52 years. ABO blood groups
      were identical between donor and recipient in all the patients. The prevalence of
      early HAT was 6.36% (7 of 110). Crude mortality with/without HAT was 22% versus
      2% (P = .001), respectively. Crude graft loss rate with/without HAT was 27%
      versus 4% (P = .003), respectively. Early HAT was shown to be primarily
      associated with intraoperative hepatic artery blood flow (93.3 mL/min recipients
      with HAT versus 187.7 mL/min recipients without HAT, P < .0001). No
      retransplantation showed early HAT. In our experience, intraoperative hepatic
      artery blood flow predicts early HAT after liver transplantation.

PMID- 22974917
TI  - Monitoring the natural evolution and response to treatment of post liver
      transplant recurrent hepatitis C using transient elastography: preliminary
      results.
AB  - OBJECTIVES: To perform a prospective analysis of changes in liver stiffness (LS)
      using transient elastography (TE) in a consecutive series of patients with post
      liver transplant (LT) recurrent hepatitis C, either left to their natural
      evolution or receiving antiviral treatment. METHODS: We examined the results from
      17 comparisons of TE (baseline vs follow-up) from 11 patients. We evaluated: (1)
      upon inclusion in the study: age, sex, genotype, time transpired since LT, and
      baseline fibrosis (F0-4; Scheuer), and (2) during the follow-up period: time
      elapsed between the two TE and either specific treatment (B) or absence of
      treatment (A). RESULTS: Mean patient age was 56.8 +/- 7.9 years, with a
      male/female ratio of 10:1. Ten of the eleven patients had genotype 1b. The median
      time transpired between the LT and inclusion in the study was 28 months (range: 6
      142 months). The mean time transpired between the two TE was 11.3 +/- 4.5 months.
      In the 11 patients from group A (9 F1/2 F2; 13 "paired" TE), a predictable
      increase in LS was produced in 10 cases and a paradoxical result was produced in
      3 cases. In the four patients in group B (3 F2/1 F1; 4 "paired" TE), a decrease
      in LS was produced in 3 cases and a paradoxical result in 1 case. CONCLUSIONS: In
      our study of patients left to their natural evolution, a slow increase of LS was
      normal. However, antiviral treatment appeared to decrease LS. TE can be very
      useful as a complementary test to biopsy for monitoring post-LT recurrent
      hepatitis C. A longer follow-up period and larger sample size could confirm these
      preliminary results.

PMID- 22974918
TI  - Study of superoxide dysmutase isozyme activities in hepatitis C virus-positive
      cirrhotic liver transplant recipients.

PMID- 22974919
TI  - Antitumor efficacy of mammalian target of rapamycin inhibitor therapy in liver
      transplant recipients with oncological disease: a case-control study.
AB  - INTRODUCTION: The reported incidences of de novo malignancy following orthotopic
      liver transplantation (OLT) are significantly greater than those in the general
      population. We have analyzed the efficacy of mammalian target of rapamycin
      inhibitor (mTORi) as immunosuppressant therapy in patients with de novo
      malignancies or those engrafted because of a primary liver cancer. METHODS: We
      performed a case-control study of patients with hepatocellular carcinoma (HCC; n
      = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven
      patients with these tumors were treated with mTORi, and 167, with calcineurin
      inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the
      CNI over 15 days, until obtaining levels of 5-10 ng/dL. RESULTS: No incidence of
      rejection, serious adverse events, or death was observed with an overall
      actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group.
      Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05).
      Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI
      patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05).
      DISCUSSION: Surprising differences in survival and tumor recurrence rates were
      observed among the mTORi-treated group compared with controls. Switching from CNI
      to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable
      to employ this strategy in liver transplant patients with primary hepatic or "de
      novo" neoplasms.

PMID- 22974920
TI  - The evolution of therapeutic strategies for biliary tract complications after
      liver transplantation over a period of 20 years.
AB  - Despite the improved overall outcomes of liver transplantation as a result of
      advances in surgical techniques and improved immunosuppressive control, biliary
      complications (BCs) continue to be the most common cause of morbidity in liver
      transplant recipients. The objectives of this study were to analyze the
      incidence, type, and management of BCs over a 20-year period. We performed a
      comparative study of two groups of liver transplant patients in our unit operated
      on by the same surgical team: group I consists of the first 300 liver transplant
      patients (1989-1992), and group II is composed of the last 300 liver transplants
      (2007-2011). We found no significant differences in the number of cases of
      biliary leakage whether or not a Kehr T-tube was used. However, there was a
      significant relationship between a greater number of anastomotic strictures and
      less use of a Kehr T-tube. In our series, there has been a decrease over the
      years in the number of surgical interventions required to resolve these
      complications and an increase in radiologic and endoscopic treatment.

PMID- 22974921
TI  - Relatives' mental health during the liver transplantation process.
AB  - OBJECTIVE: To compare the mental health of relatives of liver transplant patients
      during the three phases: pretransplantation, waiting list, and
      posttransplantation. MATERIALS AND METHODS: This follow-up study used the
      Hospital Anxiety and Depression Scale (HADS) to assess the relatives of 35 liver
      transplant patients (one relative for each patient). The anxiety-depression
      status was compared across the three liver transplant phases: pretransplant study
      (G(1)), from the first to the third month after admission to the waiting list
      (G(2)), and the 3 months after liver transplantation (G(3)). Student t test for
      paired samples was used for statistical analysis, and Cohen d calculated as an
      effect size index. RESULTS: Significant differences were observed (P = .000)
      among the three phases in anxiety and depression variables. In both, the greatest
      affective symptomatology corresponded to the phases prior to the liver
      transplantation (G(1) and G(2)) and the lowest in the post-liver transplant stage
      (G(3)). Relevant differences (large effect size) were noted between pre- and
      posttransplant phases in both HADS subscales: anxiety (Cohen d(1-3) = 1.197;
      Cohen d(2-3) = 0.817) and depression (Cohen d(1-3) = 1.228; Cohen' d(2-3) =
      1.239). CONCLUSION: Relatives show poorer mental health during the phases prior
      to liver transplantation compared with the posttransplantation.

PMID- 22974922
TI  - Biliary complications after liver transplantation using side-to-side
      choledochocholedochostomy reconstruction with or without T-tube.
AB  - BACKGROUND: Biliary complications are a frequent cause of morbidity, graft loss,
      and death after orthotopic liver transplantation (OLT). The
      choledochocholedochostomy anastomosis without a T-tube is controversial, as it
      has been related to more biliary complications. AIMS: The aims of this study were
      to determine the incidence and to identify the risk factors of post-OLT biliary
      complications after reconstruction with or without a T-tube. MATERIALS AND
      METHODS: Ninety-five consecutive adult patients with deceased donor liver
      transplantations (overall survival rate, 86.3%; mean follow-up, 22.2 months) were
      analyzed to determine the incidence and type of biliary complications in 2
      groups: choledochocholedochostomy with (45 patients, Group I) or without a T-tube
      (50 patients, Group II). The incidence of biliary complications in Groups I and
      II was 40% (18/45) and 30% (15/50), respectively (P > .05). In Group I, 49% of
      the complications were directly related to the T-tube. Biliary anastomosis
      stricture was more frequent in Group II (28% vs 8.9% in Group I; P = .018).
      Endoscopic retrograde cholangiopancreatography (ERCP) was the most common
      therapeutic procedure for the resolution of biliary complications in both groups
      (Group I, 66.5%; Group II, 58.2%). Arterial thrombosis, high pretransplantation
      Model for End-Stage Liver Disease (MELD) score, and donor obesity were identified
      as risk factors for biliary complications after OLT. CONCLUSION: OLT biliary
      reconstruction without a T-tube is not related to an increased risk of biliary
      complications, although stricutre of the anastomosis is more frequent in this
      group of patients. Donor obesity, arterial thrombosis, and high
      pretransplantation MELD score are associated with a higher incidence of biliary
      complications after OLT.

PMID- 22974923
TI  - Spontaneous clearance of HCV in HIV-hepatitis C virus coinfected liver transplant
      patients: prospective study.
AB  - BACKGROUND: Hepatitis C virus (HCV) clearance is an independent predictive factor
      for long-term survival in HIV-HCV liver transplantation patients. After 46 months
      of antiviral therapy it is achieved in up to 80% of cases. Little is known,
      however, about spontaneous viral clearance. We performed prospective study of HIV
      HCV coinfected liver transplant patients. METHODS: Between January 1, 2001, and
      December 31, 2011, we analyzed the parameters from among HIV-HCV coinfected liver
      transplant patients of donor and recipient ages, transplant cause, Model for End
      Stage Liver Disease (MELD) score, donor and recipient serology, transplant date,
      viral load before and after transplantation, immunosuppressive therapy, HCV
      recurrence, HCV viral clearance (spontaneous and duration), retransplant cause,
      and viral load before and after retransplant, as well as survival. RESULTS: The
      seven transplanted HIV-HCV coinfected patients had most commonly HCV-related
      hepatocarcinoma (n = 5, 71.42%). Three subjects (42.85%) developed HCV
      recurrences. Two patients (28.57%) were retransplanted, both due to HCV
      recurrence with one of them developing a spontaneous clearance of HCV (14.28%).
      This patient showed a preoperative HIV viral load < 50 copies IU/mL, CD4+ count
      486/MUL, HCV-RNA 2564 IU copies/mL, Anti-HBc+, and MELD 30. The donor was an 81
      year-old female who was Anti-HBc+. Immunosuppressive therapy consisted of
      cyclosporine, mycophenolate, and prednisone. One month after transplantation, the
      patient developed an acute cellular rejection episode with progression of liver
      disease secondary to the HCV recurrence (56.5 * 105 copies IU/mL). He started
      antiviral treatment (alpha-interferon and ribavirin), but due to side effects and
      interactions with the antiretrovirals, they were stopped after four doses. The
      viral load decreased spontaneously and progressively until it became negative at
      146 days after transplantation; he was retransplanted and HCV-RNA has continued
      to be negative after 772 days. CONCLUSION: Spontaneous clearance of HCV among HIV
      HCV coinfected liver transplant patients is possible. Despite no treatment, one
      patient still has no detectable HCV viral load after retransplantation.

PMID- 22974924
TI  - Andalusian registry of heart transplantation: first official adult heart
      transplant report 2010.
AB  - This is the first official report of the Andalusian Registry of Heart
      Transplantation. Since 1986, two centers in the community have been authorized to
      perform adult heart transplantation. Until 2010, 854 adult heart transplantation
      procedures were performed, which constitute the basis of the present report.
      Clinical features and survival are analyzed. The leading reason for heart
      transplantation was ischemic cardiomyopathy (34%) and nonischemic dilated
      cardiomyopathy (34%). The mean age of the recipients was 46 +/- 16 years and the
      mean age of the donors was 29 +/- 13 years. After a median follow-up of 106
      months, the mean survival was 13.4 +/- 0.6 years.

PMID- 22974925
TI  - Neurogenic stunned myocardium and cardiac transplantation: a case report.
AB  - We present the case of a 46-year-old woman referred to our center for urgent
      heart transplantation assessment, initially diagnosed as having cardiogenic shock
      of uncertain etiology. Some hours before she had suffered syncope without
      regaining consciousness. When she arrived at our hospital, the objective
      examination revealed bilateral unreactive mydriasis and absent brain-stem
      reflexes, and echocardiography showed global left ventricle wall hypokinesis
      sparing the apex. An urgent computed tomography (CT) imaging of the head was
      performed, which showed a massive subarachnoid hemorrhage and extensive cerebral
      edema. In the following hours, she fulfilled the criteria of brain-stem death and
      indeed became a multiorgan donor. The heart was rejected for transplantation
      because of the existence of left ventricle wall motion abnormalities associated
      with neurogenic stunned myocardium. Neurogenic stunned myocardium is a stress
      related cardiomyopathy that occurs after an acute brain injury. It is especially
      frequent in subarachnoid hemorrhage, where it reaches an incidence of up to 40%
      of patients. It is characterized by acute electrocardiographic changes and
      regional hypokinesis of the left ventricle wall not consistent with the coronary
      artery distribution, and is thought to be a transient condition. For this reason
      it should not constitute an absolute contraindication to cardiac donation in
      young donors with no previous cardiac disease. In our hospital during the last
      year one third of the potential heart donors had regional left ventricle wall
      motion abnormalities compatible with neurogenic stunned myocardium. With the aim
      of improving the number of cardiac donors, several strategies have been described
      to try to demonstrate the reversibility of this entity, such as dobutamine stress
      echocardiography.

PMID- 22974926
TI  - Early mortality after cardiac transplantation: comparison of demographic,
      clinical, biological and surgical variables.
AB  - Cardiac transplantation is the last alternative for those patients in terminal
      heart failure. However, its mortality is high, and approximately 20% of patients
      die in the first month after cardiac transplantation. We retrospectively reviewed
      116 patients transplanted at our center in the last 6 years. Data about clinical,
      biological and surgical variables were collected. We undertook a multivariate
      analysis in order to find differences between those patients who died in the
      first month and those who survived. We found statistically significant
      differences in total ischemia time (P = .036) and extracorporeal circulation time
      (P = .001), with those patients that died in the first month having longer times.
      We also found a statistically significant difference in the weight of the
      recipient, with those recipients that died in the first month having a higher
      weight (P = .03). No statistically significant differences were found in the
      other variables. Of particular interest was the absence of a significant
      association in both groups (survival <1 month vs survival >1 month) in the
      variables related to pulmonary hypertension (pulmonary half-time pressure,
      pulmonary systolic pressure, vascular pulmonary resistances).

PMID- 22974927
TI  - Preemptive therapy in the prevention of cytomegalovirus disease in high- and low
      risk heart transplant recipients.
AB  - Cytomegalovirus (CMV) infection remains a major complication in recipients of
      solid organ transplantation. Based on available evidence, most centers are
      committed to an aggressive strategy, especially in high-risk patients, consisting
      of the use of universal prophylaxis in the posttransplantation period of maximum
      risk (3 months). In seropositive recipients there is no ideal model for
      prevention, although there is more acceptance in the international community for
      preemptive therapy. This paper shows the results obtained after analysis of a
      cohort of 86 patients undergoing heart transplantation in 2005-2011 at the Virgen
      del Rocio University Hospital, Seville. The 86 patients followed a strategy of
      preemptive therapy for both high- and low-risk recipients based on the use of
      antivirals for a variable period of ~3 weeks when rising antigenemia was
      detected, determined by polymerase chain reaction above a set threshold. The
      incidence of CMV disease in our cohort was 4.6%. There are no data available from
      randomized clinical trials to establish which of the 2 strategies is more
      effective and safer in these patients, although there is a little experience with
      preemptive therapy in high-risk patients. Given our positive results and
      considering the adverse effects of antiviral prophylaxis derivatives, together
      with the development of resistance and the economic cost, we suggest an
      individualized prevention strategy at each center.

PMID- 22974928
TI  - Lung volume reduction surgery after lung transplantation for emphysema-chronic
      obstructive pulmonary disease.
AB  - Lung Volume Reduction Surgery (LVRS) has become a palliative treatment for
      patients with advanced emphysema and disabling dyspnea. After single lung
      transplantation in chronic obstructive pulmonary disease, LVRS may be indicated
      to improve graft dysfunction caused by native lung hyperinflation compressing the
      grafted lung. This common complication is the subject of our study, which showed
      LVRS to be helpful to manage this situation. We performed an observational
      retrospective and descriptive study using the data of 293 patients transplanted
      in our center between January 1996 and October 2011. Some of the patients who
      underwent a single lung transplantation developed native lung hyperinflation
      years after the transplantation, interfering with respiratory function due to
      graft compression.

PMID- 22974929
TI  - Lung cancer in patients with lung transplants.
AB  - OBJECTIVE: The aim of our study was to describe the incidence of lung cancer in
      patients after lung transplantation (LT). MATERIALS AND METHODS: We performed an
      observational, retrospective, descriptive study based on data from 340 patients
      undergoing lung transplantation between October 1993 and December 2010. We
      collected data about the donors, recipients, intra- and postoperative periods,
      and survivals. RESULTS: We identified 9 (2.6%) patients who developed lung cancer
      after LT. Their average age was 56 +/- 9.3 years (range, 18-63). All cases were
      men with 8/9 (88.8%) having received a single lung transplant. All cancers
      developed in the native lung. The indications for transplantation were: emphysema
      type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary
      fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers.
      All of the COPD patient were affected. The interval from transplantation to
      diagnosis was 53.3 +/- 12 months (range 24-86). Survival after cancer diagnosis
      was 49.3 +/- 6.3 (range = 0-180) months. CONCLUSIONS: LT was associated with a
      relatively high incidence of lung cancer, particularly in the native lung. In our
      series, lung cancer was related more to patients with emphysema-type COPD and a
      history of smoking. We believe that these patients should be closely followed to
      establish the diagnosis and apply early treatment.

PMID- 22974930
TI  - Association of topical amphotericin B lipid complex treatment to standard therapy
      for rhinomaxillary mucormycosis after liver transplantation: a case report.
AB  - Solid organ transplantation is becoming increasingly more common in the treatment
      of end-stage organ failure. The advent of newer immunosuppressive protocols and
      refined surgical techniques has allowed therapy to become standard care.
      Infection is a major and frequently life-threatening complication after
      transplantation and the incidence of opportunistic fungal infections in organ
      transplant recipients ranges from 2%-50% depending on the type of organ
      transplanted. We present a case of rhinomaxillary form of mucormycosis infection
      after liver transplantation. The succession of multiple risk factors in a torpid
      postoperative period was a key factor in the development of this disease.
      Multidisciplinary management with an early diagnosis, aggressive surgery, and
      intravenous and topical antifungal therapy care were definitive for the
      eradication of infection. The goal of the present report was to show efficacious
      management including the association of topical treatment with amphotericin B
      complex lipid to standard therapy and the absence of side effects.

PMID- 22974931
TI  - Early detection of biliary complications and graft rejection in a non-RH
      Identitical liver transplant recipient from a non-heart-beating donor: a case
      report.
AB  - Because of a shortage of organs, non-heart-beating donors have been proposed to
      be a possible source of grafts for orthotopic liver transplantation. Herein, we
      have presented a blood group A+ patient with primary biliary cirrhosis, who
      underwent orthotopic liver transplantation from a non-heart-beating blood group A
      donor. On day 5 after transplantation the patient displayed a low hemoglobin
      levels as well as an increased total bilirubin with progressive encephalopathy,
      hypotension, and oligoanuria on day 11. The patient responded to steroid
      treatment. We assume the main cause of organ dysfunction was a passenger
      lymphocyte syndrome (ABO-Rh incompatibility). Biliary complications were detected
      at a 6-month follow-up visit by increased hepatic enzymes. We thus concluded that
      it is useful to take Rh group into account.

PMID- 22974933
TI  - History of eurotransplant.
AB  - In 1967, the Dutch immunologist Jon van Rood called Eurotransplant into life.
      From the beginning it was a non-profit private foundation. Initially it was a
      loose cooperation, where tissue typing laboratories and transplantation centers
      joined to achieve a better result for their kidney patients, a longer survival
      based on better immunological matching from a bigger donor pool. Other centers
      from the Benelux states, Germany and Austria soon joined the first few
      cooperating centers. Switzerland was also a member of Eurotransplant, but left
      the organization in 1978. Based on the pioneering work of the Leiden
      histocompatibility lab, the allocation system became more and more sophisticated
      and was extended to other solid organs. Since the 1980s Eurotransplant has
      allocated donor livers, hearts, and pancreas. Thereafter, the allocation also
      included lungs and small bowel. From 1996 a new kidney allocation system, the
      ETKAS, was introduced, and after the Acceptable Mismatch program and the
      Eurotransplant Senior Program (known unofficially as "old-for-old" program) were
      introduced. The main principle remains to adapt the allocation rules continuously
      according to the newest scientific data serving all organs. In 1991 the German
      reunification centers in the former Eastern Germany became part of
      Eurotransplant. In 1999, Slovenia, and in 2007 Croatia joined Eurotransplant. For
      the transplant centers in these two countries, membership meant positive changes
      and is regarded as a success story. Both donor numbers and transplant
      possibilities increased and equal chances are assured for their patients on the
      common Eurotransplant waiting list. Hungary, joining Eurotransplant next year,
      hopes to experience the same.

PMID- 22974934
TI  - Decrease in cold ischemic times as a result of protocol changes of urgent
      immunogenetic testing during cadaveric kidney transplantation in Hungary.
AB  - BACKGROUND: Based on national ethics committee permission, the procedure of
      urgent immunogenetics testing prior to cadaveric kidney transplantation was
      changed in Hungary from January 1, 2011 allowing HLA typing of the donor and
      prospective crossmatching using peripheral blood samples from the donor prior to
      the definitive declaration of brain death. The aim of the current study was to
      compare key indicators of transplantation primarily cold ischemic time [CIT],
      between time periods with outcomes. METHODS: The following indicators were
      systematically collected prospectively and retrospectively for each deceased
      heart-beating donor transplantation between January 1, 2010 and October 31, 2010
      (n = 114) versus January 1, 2011 and October 31, 2011 (n = 91): CIT for the first
      and second kidney; laboratory turnaround times (TAT), and time for final
      preparation of the selected recipient. RESULTS: As a result of the new procedure,
      the CIT for the first kidney decreased from 16.5 +/- 3.5 to 12.4 +/- 3.2 hours (P
      < .001). Similarly, for the second kidney the parameters were a 19.8 +/- 3.4
      versus 16.0 +/- 3.8 hours (P < .001). As a consequence of more hands-on time in
      the laboratory, the TAT increased from 5.6 +/- 0.8 hours to 7.2 +/- 1.1 hours
      (TAT1) followed by an additional 4.2 +/- 1.0 hours (TAT2). We also compared the
      times necessary for preparation of immunologically suitable recipients for
      transplantation, namely, 9.5 +/- 2.3 hours in the earlier system, increasing to
      15.5 +/- 4.3 hours during the new procedure. CONCLUSION: As a consequence of the
      procedural change, the CIT parameter decreased significantly for both kidneys,
      which may have contributed to improved short-term outcomes of transplantation.
      The time available for final preparation of selected recipients was increased
      allowing improvements in CIT.

PMID- 22974935
TI  - Deviceless low-pressure operation; a cost-effective way to reduce CO2-induced
      barotrauma during hand-assisted laparoscopic donor nephrectomy.
AB  - Between March 2008 and March 2011, hand-assisted laparoscopic donor nephrectomles
      were performed on 70 patients. Following the first 26 cases undertaken based on
      guidelines in the literature, we modified the procedure to avoid barotrauma to
      the kidney caused by the usual 12-13 mm Hg CO(2) pneumoperitoneum or
      pneumoretroperitoneum. The perirenal CO(2) pressure, therefore, was decreased to
      8 mm Hg from the beginning of the surgery; the operation was performed without
      using a handport. Our early experience with the modified technique suggested that
      the safety and duration of the procedure were not affected but the incidence of
      delayed graft function due to barotrauma was decreased, a cost-effective
      improvement.

PMID- 22974936
TI  - Functional and morphological changes in kidneys from marginal donors.
AB  - Despite the increased number of cadaver donors and overall organ
      transplantations, we have observed a dramatic increase in the waiting list. We
      evaluated transplantations performed using marginal (n = 63) and "ideal" or
      optimal donors (n = 86). Donor and recipient functional and histopathological
      data were studied at 1 and 5 years after transplantation. Among the marginal
      donor group, we investigated whether the age or pre-existent hypertension in the
      donor showed a strong impact on the functional deterioration of the grafts.
      Twenty-three graftectomies were performed in marginal, and 39 in ideal recipients
      (P = .002). Evaluating graft function, at 5 years, we observed the serum
      creatinine level (P = .0001) and the estimated glomerular filtration rate (P =
      .003) are significantly different between the two groups. At this time there was
      a significant difference in the serum creatinine level of patients who were older
      than the age of 55 years compared with those who showed hypertension (P = .0003).
      Evaluating morphological changes in the kidneys, acute rejection episodes (P =
      .0004) and interstitial fibrosis/tubular atrophy (P = .002) were significantly
      greater among the marginal versus the ideal groups. At 1 year after kidney
      transplantation, despite no significant difference regarding renal function, they
      were significant in the histology of marginal versus ideal donor kidneys.

PMID- 22974937
TI  - Mental representations of the new organ and posttransplant patients' anxiety as
      related to kidney function.
AB  - Transplant patients' representations of their illness, body, and emotional state
      significantly influence their recovery. In this study, our primary aim was to
      examine the possible connections between emotional factors, body and illness
      representations, and renal function after 58 kidney transplantations. To measure
      mental representations of transplanted kidneys, we developed a projective drawing
      test. Other assessment instruments were the Beck Depression Inventory,
      Spielberger's State and Trait Anxiety Scale, and an in-house questionnaire. We
      also measured conventional kidney function markers, such as serum creatinine and
      urea levels. Analysis of our results revealed that patients with higher anxiety
      levels drew significantly larger kidneys in their projective drawing tests, and
      displayed significantly higher 10-day creatinine and urea level leading us to
      consider interrelations of an organ's intrapsychic integration and kidney
      function. If the graft is not integrated mentally in the body image, the
      representations of the "foreign body" can be associated with such psycho-neuro
      immunologic processes of anxiety, which eventually may lead to adverse
      physiological effects on kidney function.

PMID- 22974938
TI  - Role of early systemic inflammatory response in simultaneous pancreas-kidney
      transplantation.
AB  - Pancreas grafts are susceptible to surgical complications mostly related to
      exocrine secretions and the low microcirculatory blood flow through the gland.
      During simultaneous kidney-pancreas transplantation, the systemic response
      depends on reperfusion of two organs acute graft pancreatitis, immunotherapy,
      coagulopathy, bleeding, and other factors. We performed a retrospective review of
      10 adult simultaneous pancreas-kidney transplant patients to evaluate progression
      of early postoperative inflammation in the absence of infection. All patients
      were treated with four-drug therapy. We performed analyses of procalcitonin
      (PCT), C-reactive protein, serum creatinine, amylase, and lipase levels over the
      first 5 postoperative days. Relatively high peak PCT levels (maximum 130 ng/mL)
      were reached within 24 to 48 hours postoperatively followed by a moderate
      decrease. Consistent with this observation, the serum creatinine, amylase, and
      lipase levels decreased continuously to normal concentrations within the first
      week. The increased PCT levels seemed depend upon the surgical procedure and
      intraoperative events. PCT was superior to C-reactive protein to discriminate
      infection from inflammation in this setting. The dynamics of PCT levels, rather
      than absolute values, seemed to be important. Lack of a decrease in PCT levels
      after the peak, suggested an infectious complication or the development of
      sepsis. Monitoring and assessment of PCT levels may help in early recognition of
      infection and institution of therapy.

PMID- 22974939
TI  - The safe introduction of angiotensin-converting enzyme inhibitor in renal
      allograft recipients.
AB  - Antihypertensive and renoprotective treatment with angiotensin-converting enzyme
      inhibitor (ACEI) or angiotensin II receptor blocker is indicated in almost all
      chronic renal failure patients. However, this treatment is not widely used for
      renal allograft recipients mainly because of the potential side effects,
      including a decrease in renal function as well as onset of hyperkalemia or
      anemia. Herein we investigated the effects of ACEI introduction to hypertensive
      renal transplantation patients who did not display renal artery stenosis. At
      least 2 months after transplantation, we exchanged amlodipine (5 mg) for either
      ramipril or perindopril (5 mg) in 25 patients who were free of renal artery
      stenosis as determined indirectly by measuring the renal arterial resistance
      index with the noninvasive, inexpensive Doppler ultrasound method. The resistance
      index was evaluated again at 2 weeks. Systolic and diastolic blood pressure,
      serum creatinine, calculated creatinine clearance, serum potassium, hemoglobin
      and hematocrit were also measured before as well as at 2, 4, and 12 weeks after
      conversion to ACEI. The conversion did not change the mean renal arterial
      resistance index, nor did it influence renal function or blood count, and it was
      equally effective for controlling blood pressure. The serum potassium level
      increased at 2 and 4 weeks; however, it was within the normal range in all
      patients. Our data suggested that measurement of the renal arterial resistance
      index is a noninvasive, inexpensive, and reliable preselection method before
      introduction of ACEI in renal allograft recipients.

PMID- 22974940
TI  - Measurement and clinical significance of interleukin 28B in hepatitis C virus
      infected liver transplant patients.
AB  - One-third of the liver transplantations are performed because of hepatitis C
      cirrhosis all over the world and also in Hungary. The recurrence rate is
      practically 100%, influencing graft and patient survivals; within 5 years
      cirrhosis develops again in 20% to 30% of cases. The therapy is pegylated
      interferon alpha-2a and alpha-2b plus ribavirin as for nontransplanted subjects
      with the goal to eradicate the virus and maintain graft function. In 25% to 45%
      of treated patients, it is possible to achieve a sustained virological response
      (SVR). The response is influenced by viral, donor, and recipient factors. We
      investigated the genotype of 68 liver recipients transplanted because of
      hepatitis C virus (HCV) infection between September 1998 and February 2011. We
      focused on the interleukin (IL) 28B gene locus single nucleotide polymorphism
      found on chromosome 19; the rs12979860 minor allele (homozygous [wild TT and CC],
      heterozygous [CT]) in relation to the interferon response. Ten percent of the
      patients belonged to the CC, 62% to the CT, and 28% to the TT group, and 83% of
      the CC group became negative or therapy is still ongoing. The CT genotype reached
      15.4% SVR with ongoing treatment for most patients. In TT carriers showed a 23.5%
      SVR. Our patients formed a homogenous group regarding the surgical team, the
      therapy, and the HCV genotype. Ninety percent belonged to the possible "hard to
      treat" group. The 10% CC group gave the highest number of SVR and HCV polymerase
      chain reaction negativity upon antiviral therapy. Regarding our results, one has
      to take in consideration the small patient number and the fact that the cirrhotic
      patients were listed for transplantation where they could not be treated or
      became therapy-resistant. IL28B is just one predictive factor among others for
      successful posttransplant HCV therapy; further examinations are needed to fully
      understand its role.

PMID- 22974941
TI  - Significance of mycophenolate monitoring in liver transplant recipients: toward
      the cut-off level.
AB  - Mycophenolate mofetil blocks the "de novo" -purine synthesis to reduce the
      incidence and severity of acute rejection episodes. There has been an increased
      interest in utility of monitoring mycophenolic acid (MPA) levels, however
      currently the MPA monitoring is not part of the protocol following liver
      transplantation. We assessed whether trough MPA monitoring could be advisable in
      liver transplant patients or not. For this reason MPA levels of 56 liver
      transplants were measured on 3, 5, 10, 14, 21, 30, 60, and 180 posttransplant
      days. The optimal cut-off of MPA level (>=1.73 mg/L) for all (56) and >=1.34 mg/L
      for ciclosporin-treated- and >=1.98 mg/L for the tacrolimus-treated transplants
      were calculated by statistical analysis to reduce the incidence of acute
      rejection. MPA concentrations of 3 days period before the day of clinical
      diagnosis acute rejection were well below the cut-off value. Only 3 (16%) out 19
      patients with acute rejection had higher MPA levels than the cut-off value on the
      day of diagnosis of acute rejection. In conclusion, our data suggests that MPA
      predose level monitoring, especially in the early "filling phase" after
      transplantation, is applicable in liver allograft recipients given adjunctive
      MMF, protecting them from the ineffective immunosuppression.

PMID- 22974942
TI  - Predictive factors of sustained virological response for recurrent hepatitis C
      virus after liver transplantation: the hungarian experience.
AB  - Recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) occurs
      consistently. Early initiation of combined antiviral treatment (AVT) has become a
      standard treatment seeking to achieve sustained virological response (SVR). We
      evaluated the files of 108 HCV-positive patients between 2003 and 2010. Seventy
      two (72) experienced recurrent HCV within 12 months, 31 of whom completed the AVT
      (43%) but 9 (29%) exhibited SVR. Factors with impacting SVR were male recipient,
      no fatty changes in the donor liver, short warm ischemia time, cyclosporine-based
      immunosuppression, neither infective, septic or bleeding complication nor acute
      rejection episode and a rapid viral response to AVT. De novo diabetes, and
      unsuccessful AVT prior to OLT were strongly associated with a a failed SVR. The 1
      and 3-year cumulative patient survival rates trended to be better in cases of
      SVR compared with nonresponders (100% and 100% versus 94% and 89%; P = .07).

PMID- 22974943
TI  - Activity of ulcerative colitis before and after liver transplantation in primary
      sclerosing cholangitis: the Hungarian experience.
AB  - Primary sclerosing cholangitis (PSC) is a common cause for liver transplantation
      (OLT) in Europe. It is frequently associated with inflammatory bowel disease
      (IBD). PSC associated IBD often runs a quiescent course but becomes more
      aggressive after OLT in some patients. Our aim was to evaluate the activity of
      IBD in PSC patients before and after OLT in Hungary. We retrospectively analyzed
      data from 411 whole-liver transplantations from 1995 to 2010 that included 41
      patients transplanted due to PSC (10%). Thirty-one PSC patients had IBD pre-OLT.
      We used the Mayo score (Disease Activity Index) to assess the severity of
      ulcerative colitis (UC) before and after OLT. Among 55% of patients who had
      pancolits, the majority (95%) were inactive or showed only mild activity before
      transplantation. After transplantation, disease activity was inactive in 10%;
      mild to moderate in 25% to 25%; and severe in 40% of cases. The Mayo score was
      higher after transplantation compared with the pretransplant level (2.91 +/- 0.9
      versus 6.64 +/- 3.7, P = .009). Retransplantations (n = 5) were performed only
      among PSC patients with colonic involvement. In conclusion, the activity of IBD
      worsens in the majority of patients after OLT. Early colectomy should be
      considered to prevent severe complications and liver graft impairment.

PMID- 22974945
TI  - Biobank concept in Poland.
AB  - Possible adverse events and reactions associated with organ procurement and
      transplantation from deceased donors require compliance with quality and safety
      standards. Shortage of organs for transplantation makes it necessary to obtain
      organs from nonstandard (expanded-criteria) donors. This increases the risk of
      disease transmission with the graft which is difficult or impossible to identify
      before transplantation. The long-term access to biologic material of organ donors
      and recipients proffers the possibility to evaluate serious adverse reactions as
      well as to improve the quality and safety in transplantation medicine.
      Implementation of the above-mentioned tasks requires a Biobank whose aims are: to
      gather and long-term storage sera, lymph nodes, and other tissues of deceased
      organ donors for analysis of their biologic properties; to gather and store organ
      recipient sera; to determine methods to store biologic material in a manner
      enabling identification of the donor, organ, and recipients; and to provide
      electronic record keeping. Tactical tasks of a Biobank are: to carry out new or
      verify results of previously performed testing of deceased donors and recipients
      as controls to evaluate transmission of infection; to perform genetic material
      testing (NAT) to verify and confirm serologic tests, eg, determination of HIV
      RNA/DNA in donors at risk of infections; to discover rare diseases in donors and
      recipients whose detection before transplantation is difficult because of the
      time constraints related to organ storage or the lack of available methods (eg,
      sponge encephalopathies); to perform biochemical or genetic tests to evaluate
      neoplasia transfer from donor to recipient; and to reexamine HLA typing in cases
      of immunologic complications.

PMID- 22974946
TI  - Transplantation ethics: are we approaching the crossroads?
AB  - Ethical issues of organ transplantation are of extreme importance to involved
      physicians and to society. The basic principle is that the donor cannot be
      considered as a commodity; financial incentives must not occur. Regarding
      deceased-donor organ transplantations, ethical issues are related to the consent
      for donation, determination of death, and principles of organ allocation. Living
      donors should be healthy, giving free consent after being fully informed about
      the risks of the procedure. Transplant professionals have a double responsibility
      because they must remember about the rights of the organ recipient as well as of
      the donor. Because of the organ shortage we commonly use organ recovery from
      donors after cardiac arrest and extend the living-donor pool, practices that may
      influence some important ethical principles. A proper detailed determination of
      donor death is of utmost importance. The dead donor rule must be preserved.
      However category III non-heart-beating donors (so-called controlled cardiac
      arrest) raise doubts as to the time of the decision to transfer the dying (not
      yet dead) patient to the operating room to withhold supportive treatment. In
      certain centers, not quite healthy living donors are being used; they are called
      extended-criteria or complex donors. Although organ trade is condemned, some
      workers agree to use as complete strangers donors, obviously believing in pure
      altruistic motivation of such donors without the additional incentives. Finally,
      is the trend to consider utility in organ allocation justified? It seems that
      quite soon we may need a new transplantation ethics code that is not totally
      directed by transplant professionals exclusively to the needs of potential
      recipients.

PMID- 22974947
TI  - Survey on attitudes and knowledge on the organ recovery from deceased donors in
      Roman Catholic nuns and priests.
AB  - Deceased donors (DD) organ recovery rate in Poland has never been satisfactory
      but over the years kidney transplantation from deceased donors has reached the
      level of 26 transplants/pmp. In 2007 due to a number of reasons, a dramatic fall
      of organ recovery rate from deceased donors (DD) occurred. The survey on public
      attitude toward organ transplantation carried out in the same year showed a large
      reduction of the public trust toward medical profession. Since then, the number
      of kidney transplantations has never come back to its level from 2006, regardless
      of a positive attitude toward organ transplantation. The attitude and knowledge
      survey was recently carried out in 100 physicians and 100 nurses employed in one
      large district hospital. The results of the attitude survey among the hospital
      staff showed that the level of knowledge among nurses corresponded to their age
      and the time since graduation. Younger nurses showed much more appreciation and
      knowledge toward recovery of organs from the deceased donors. Survey among
      physicians indicated some hesitation toward recognition of the brain death. In
      the present paper results of the survey on attitude and knowledge toward organ
      transplantation among nuns (98 nuns), priests (100 priests) and students (98
      students) of the Theological School living in the same area are presented.
      Despite quite high (>60%) acceptance of the deceased donation, one third of
      questioned population showed lack of knowledge not only on existing legal
      regulations, but also of important documents issued by the Catholic Church.
      CONCLUSIONS: Improvement of transplantation program in Poland requires extensive
      educational program among various parts of the society: most importantly among
      physicians, nurses and priests. The Partnership for Transplantation program has
      been directed to achieve these goals.

PMID- 22974948
TI  - Partnership for transplantation: a new initiative to increase deceased organ
      donation in Poland.
AB  - Despite the long-standing history of transplantation, the shortage of organs has
      remained its most restrictive factor. In 2010, the number of actual deceased
      organ donors in Poland was 13.5/million population (pmp). However, a huge
      difference in organ recovery rates is evident between various regions, eg, 32
      pmp, in western Pomerania compared with 1-3 pmp in southern districts. A
      substantial number of patients who die while awaiting organ transplantations
      could be saved were effective programs able to overcome barriers in deceased
      organ donation. Such programs, eg, the European Donor Hospital Education Program,
      Donor Action, European Training Program on Organ Donation, United States
      Collaborative in Donation were introduced several years ago, but after transient
      improvements there has not been real progress. A new comprehensive program
      Regional Partnership for Transplantation-was initiated a year ago in 4 districts
      of southern Poland by the Polish Union for Transplantation Medicine. The letter
      of intent to activate the donation program was signed by the local
      administration, the president of the local medical school, president of the
      Physician's Chamber, transplant centers, the Polish Union for Transplantation,
      and the Polish Transplant Coordinating Center. The plan of action included
      training of in-hospital coordinators, visits to all regional hospitals in company
      of a representative of the hospital founding body, examination of the real
      donation pool and the need for participation in a donation program training and
      education of the hospital staff in legal and organizational aspects of donation,
      brain death recognition, and various aspects of donor care. In addition, the
      program included communication skills workshops for intensive care unit
      physicians (with participation of 2 actors, an experienced anesthesiologist, and
      a psychologist), lectures for high school and university students and for
      hospital chaplains as well as alumni of higher seminaries. The preliminary
      results (after the first year) showed 40%-70% increases in activity of the local
      hospitals in the organ donation process.

PMID- 22974949
TI  - Grand rounds to provide feedback on procurement activities.
AB  - INTRODUCTION: The Argentine Society of Transplants has set in motion an activity
      called Grand Rounds to Provide Feedback on Procurement Activities with the
      purpose of informing, training, and creating awareness by providing information
      about the evolution of transplanted patients. OBJECTIVE: To measure, describe and
      analyze the impact that the transplant results presented at the rounds had on
      participants. RESULTS: One hundred and fifty-eight surveys were conducted. The
      respondents' average age was 40.06 years (95% confidence interval [CI 95%] 38.39
      41.73) including 52.08% women (CI 95%: 43.92%-60.24%); 77.14% physicians (CI 95%:
      84.09%-70.18%); 7.85% nurses (CI 95%: 3.4%-12.31%;) and 4.28% surgical nurses and
      other professional (CI 95%: 0.93%-7.64). When asked how comforted they felt when
      they learnt about a transplantation, the score prior to the round was 4 (CI 95%:
      3.79-4.20) and after it, 4.8 (CI 95%: 4.69-4.90; P < .05). When asked about the
      transparency of the donation process, the average score before the round was 4.16
      (CI 95%: 3.96-4.36) and after it, 4.76 (CI 95%: 4.67-4.86; P < .05). When asked
      how proactive they considered themselves before, before the average score was
      3.54 (CI 95% 3.30-3.78) and post-round, 4.53 (CI 95%: 4.38-4.67; P < .05). When
      asked if they thought that this activity might be useful for them to manage
      future donors, 97.41% (CI 95%: 89%-96.98%) of respondents answered affirmatively.
      The answers to the question whether they thought this activity might increase
      donation were affirmative in 92.99% of cases; "Don't know", 6.36%; and negative
      in less than 1%. When consulted about their feelings, the preferred one was
      "happiness" for 46.82% of respondents; followed by "satisfaction" for 29.36% and
      "emotion" for 23.80%. The analysis of the open-ended questions revealed that the
      rounds were perceived as closure of the procurement-transplantation process.
      CONCLUSIONS: This widely accepted tool was viewed as a vehicle to interconnect
      links in the work process from organ procurement to transplantation.

PMID- 22974950
TI  - Decompressive craniectomy and brain death prevalence and mortality: 8-year
      retrospective review.
AB  - Decompressive craniectomy (DC) is a surgical practice that has been used since
      the late 19th century. The cerebral blood flow increase after the performance of
      a DC can delay and even prevent the development of cerebral circulatory arrest
      and brain death (BD). We aimed to determine the prevalence of BD, the use of DC,
      and the evolution to BD with versus without DC. This retrospective,
      observational, cross-sectional study was performed in a single high-intensity
      center in Argentina from January 2003 to December 2010. Inclusion criteria were
      all patients with Glasgow Coma Score of at most 7 on admission or during their
      stay in the intensive care units. Exclusion criteria were patients with
      incomplete data. In cases of death, we assessed whether they fulfilled BD
      criteria or if the cause of death was a cardiac arrest (CA). The 698 patients
      considered for analysis showed a 60% (n = 418) global mortality rate. The causes
      were: CA (n = 270); BD (n = 108) and others considered to be "undefined," namely
      not assessed completely for the diagnosis of BD (n = 40). According to diagnosis
      category, traumatic brain injury (TBI) was largest (nearly 50%). The DC group (n
      = 206) showed significant differences regarding sex and diagnosis category versus
      no DC group. Mortality was significantly lower in this group (48% versus 65%, P <
      .001). No significant differences were observed comparing causes of death (CA,
      BD, or undefined). The use of DC did not influence the frequency of BD
      development (24% versus 26%, P = .72). The average DC rate was 30% and of BD 16%.
      The prevalence of DC and better survival were recorded compared with subjects
      without DC. The prevalence of BD was lower than expected in accordance with
      national registries; however, among our group, DC did not seem to modify the
      evolution to BD.

PMID- 22974951
TI  - Establishing a brain-death donor model in pigs.
AB  - INTRODUCTION: An animal model that imitates human conditions might be useful not
      only to monitor pathomechanisms of brain death and biochemical cascades but also
      to investigate novel strategies to ameliorate organ quality and functionality
      after multiorgan donation. METHODS: Brain death was induced in 15 pigs by
      inserting a catheter into the intracranial space after trephination of the skull
      and augmenting intracranial pressure until brain stem herniation. Intracranial
      pressure was monitored continuously; after 60 minutes, brain death diagnostics
      were performed by a neurologist including electroencephalogram (EEG) and clinical
      examinations. Clinical examinations included testing of brain stem reflexes as
      well as apnoe testing; then intensive donor care was performed according to
      standard guidelines until 24 hours after confirmation of brain death. Intensive
      donor care was performed according to standard guidelines for 24 hours after
      brain death. RESULTS: Sixty minutes after brain-death induction, neurological
      examination and EEG examination confirmed brain death. Intracranial pressure
      increased continuously, remaining stable after the occurrence of brain death. All
      15 animals showed typical signs of brain death such as diabetes insipidus,
      hypertensive and hypotensive periods, as well as tachycardia. All symptoms were
      treated with standard medications. After 24 hours of brain death we performed
      successful multiorgan retrieval. DISCUSSION: Brain death can be induced in a pig
      model by inserting a catheter after trephination of the skull. According to
      standard guidelines the brain-death diagnosis was established by a flat-line EEG,
      which occurred in all animals at 60 minutes after induction.

PMID- 22974952
TI  - Impact of catastrophic brain injury guidelines on donor management goals at a
      level I trauma center.
AB  - BACKGROUND: An organ procurement organization (OPO) and a level I trauma center
      developed catastrophic brain injury guidelines (CBIGs) to assist in the care of
      severely brain-injured adult patients before brain death. The CBIGs provided a
      set of clinical guidelines to maintain patient stability and optimize opportunity
      for organ donation. OBJECTIVE: The aim of this study was to determine if the use
      of the CBIGs affected the OPO's ability to achieve donor management goals (DMGs)
      before organ recovery. METHODS: We conducted a retrospective analysis comparing
      the number of DMGs met in the hospital's donors before and after the CBIGs were
      used. The analysis included 133 cases; 67 donors in the pre-CBIG data and 66
      donors in the post-CBIG review. Donor management goals measured included:
      systolic blood pressure >100 mm Hg; 1 pressor <=10 MUg/kg/min; urine output 1-2
      mL/kg/h; pO(2) >100 mm Hg; Na <160 meq/L; pH within normal limits (7.35-7.45);
      temperature 36.5-37.5 degrees C; arterial line in place and central line in place
      with monitor. RESULTS: After the introduction of the CBIGs, 78% of DMGs were met
      more often, with 1 goal (Na) remaining equivalent and 2 goals (pO(2) and pH) met
      less often. Increase in achievement of individual DMGs ranged from 4% to 33%. The
      pre-CBIG cases averaged 2.90 missed goals per donor compared with an average of
      1.79 in the post-CBIG data. Only 5 pre-CBIG donors (7%) achieved all of the DMGs.
      That figure rose to 12 donors (18%) in the post-CBIG data. CONCLUSIONS: While
      other factors may have contributed to our results, we think that there is a
      positive relationship between the CBIGs and the increase in meeting most DMGs. As
      we refine our donor management, we will focus on the factors we met less
      successfully. Ultimately, the use of the CBIGs before brain death led to more
      stable donors, maximizing transplantable organs.

PMID- 22974953
TI  - Establishing a donation after cardiac death model in pigs.
AB  - INTRODUCTION: Due to the lack of human donors, several strategies have sought to
      expand the organ pool. Efforts to characterize donation after cardiac death (DCD)
      have included studies of cell viability, histological and immunohistochemical
      changes, and oxidative stress, which is known to negatively impact graft
      survival. A large animal model would be useful for these inquiries. Therefore, we
      sought to establish a DCD animal model in pigs. METHODS: We simulated non-heart
      beating donation Maastricht II and III conditions in 24 pigs. Cardiac
      fibrillation was induced using 9-V direct current. After various times of
      ventricular fibrillation (1-10 minutes) with no mechanical and/or medical
      treatment to achieve cardiac output, reanimation was performed for 30 minutes
      prior to multiorgan donation. Then, a neurological status was performed. Blood
      samples were obtained at defined times tissue samples were stored in liquid
      nitrogen and subsequently embedded in paraffin and subjected to further analysis.
      RESULTS: We established a DCD pig model in our laboratory by inducing cardiac
      fibrillation. Up to now, only DCD donation according to the Maastricht criteria
      II and III has been performed, but establishing all Maastricht criteria of DCDs
      seems to be feasible. CONCLUSION: A DCD model in pigs enables us to characterize
      organ quality more precisely as well as evaluate amelioration of storage
      conditions and donor treatments in a large-animal model.

PMID- 22974954
TI  - Graft arteriosclerosis and glomerulosclerosis correlate with flow and resistance
      to machine perfusion in kidney transplantation.
AB  - INTRODUCTION: Machine perfusion to preserve kidneys for transplantation has grown
      over the past decade with demonstrated diagnostic and therapeutic benefits. Flow
      and resistance patterns are used to predict delayed graft function (DGF) and
      posttransplant graft survival. Preimplantation biopsies obtained serve a similar
      role in evaluating kidneys especially if they meet expanded criteria. The
      reliability of available data is greater if there is a correlation among various
      forms of assessment. In this study we attempted to study serial pump parameters
      that might correlate with abnormal findings in preimplantation biopsies and
      subsequently in outcomes after transplantation. METHODS: Two hundred sixty-eight
      kidneys were assessed for changes in pump pressures in mm Hg, flow in mL/min,
      resistance in mm Hg/mL/min, and temperature in  degrees C at 15-minute intervals.
      Allografts were separated into two groups on the basis of pathology; group 1
      showed abnormal (AH) and group 2 normal histology (NH). AH was defined by the
      presence of glomerulosclerosis in >=10% of sampled glomeruli or arteriosclerosis
      affecting at least 10% of the arterial lumens of sampled intrarenal arteries. We
      assessed discordance between frozen and permanent sections. Measured clinical
      outcomes included DGF, 1-year graft survival, 1-year serum creatinine and
      estimated glomerular filtration rate (eGFR). Statistical analysis was performed
      using a paired Student t test and chi-square analysis. RESULTS: Compared to NH
      kidneys, those with AH showed uniformly significant lower flow rates and higher
      resistances during the entire perfusion. Graft pathology did not predict DGF (70%
      versus 60%, P = .45). However, 1-year graft survival (96.2% versus 80%, P = .07)
      and eGFR (58 versus 48 mL/min, P = .19) were lower among kidneys with AH, though
      these matrics did not reach significance. CONCLUSION: Preimplantation biopsy
      findings correlated with flow and resistance to perfusion. If a discrepancy is
      evident upon evaluation of a donor kidney, a repeat biopsy is prudent prior to
      discarding or using the organ.

PMID- 22974955
TI  - Effect of increased pressure during pulsatile pump perfusion of deceased donor
      kidneys in transplantation.
AB  - INTRODUCTION: Pulsatile pump perfusion of potential kidneys for transplantation
      is known to decrease the rate of delayed graft function (DGF) and improve their 1
      year survival. Flow and resistance parameters are often used to determine the
      suitability of kidneys for transplantation. Kidneys with low flow rates are often
      subjected to higher pressures to improve flow. This study evaluated the effect of
      higher pump pressures on posttransplant renal function. METHODS: We performed a
      retrospective analysis of 73 deceased donor kidneys preserved using pump
      perfusion (LifePort) at our center between May 2006 and September 2009. We
      calculated the mean pump pressure (MP) for the duration of perfusion of each
      kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with
      the following formula: (MP = DP + 1/3 (SP - DP). The kidneys were divided into a
      low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff
      value of 23 mm Hg. The two groups were then compared for differences in perfusion
      dynamics and primary endpoints including DGF and 1-year graft survival.
      Statistical analysis was performed using paired Student t test and chi-square
      analysis. RESULTS: The two groups were comparable for donor age, extended
      criteria, sensitization, and cold ischemic times. They differed significantly in
      higher initial (0.65 +/- 0.4 versus 0.4 +/- 0.2, P = .01), average (0.25 +/- 0.08
      versus 0.18 +/- 0.06, P = .0006), and terminal resistance (0.21 +/- 0.07 versus
      0.17 +/- 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable
      between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006)
      with similar 1-year graft survival (87.5% versus 89%, P = .7). CONCLUSIONS:
      Perfusate flow through a kidney can be improved by increasing pressure settings
      to overcome elevated resistance. This maneuver was not associated with a lower
      rate of DGF after transplantation. One-year graft survival remained unaffected.

PMID- 22974956
TI  - Prognostic utility of hypothermic machine perfusion in deceased donor renal
      transplantation.
AB  - Pulsatile pump perfusion of kidney transplants is known to decrease delayed graft
      function (DGF) and improve 1 year graft survival when compared to static cold
      preservation. Kidneys with better flow and resistance parameters on perfusion are
      likely to have a better post transplant function. These parameters are commonly
      used to evaluate kidneys being considered for transplantation. This study
      assesses the time frame for a kidney within which it reaches optimal perfusion
      parameters. All kidneys pumped between 5/2006 and 9/2009 on a Lifeport(c) kidney
      transporter at our local organ procurement agency were studied. 190 kidneys were
      evaluated and then divided into two groups based on whether terminal flows
      increased or declined after prolonged perfusion. All kidneys were assessed for
      changes in flow (F), resistance (R) and temperature at 15 minute intervals.
      Discards, DGF and one year graft survival were noted. The Student paired t test
      and Chi-square analysis were used to compare data. A multiple logistic regression
      analysis was performed to study independent predictors of DGF on pump perfusion.
      RESULTS: For all kidneys, the mean initial flow was 59 +/- 35 mL/min which
      improved to an average flow of 128 +/- 38 mL/min with continued perfusion. The
      maximal flow and terminal flows were 148 +/- 51 and 135 +/- 38 mL/min
      respectively. The flows at 2, 4, and 6 hours was 125 +/- 41, 128 +/- 42 and 130
      +/- 39 mL/min respectively. Kidneys that improved on continued perfusion had a
      significantly lower discard rate (20 vs 34% p < 0.05), but a higher incidence of
      DGF (64 vs 39%, P < .05). One year graft loss (death censored) was comparable in
      the two groups. (4/42 vs. 3/33, P = .94). Resistance at 2, 4, and 6 hours was
      predictive of DGF, as was donor anoxia and cerebrovascular accident (CVA) as the
      cause of death. CONCLUSIONS: Kidneys on pulsatile pump perfusion tend to show
      improved flows and decreased resistance over time. The average flow for a kidney
      is reached by 2 hours. Those kidneys that start with lower flow rates that
      improve after 2 hours with continued perfusion are less likely to be discarded
      but are still associated with a greater incidence of delayed graft function.
      Resistance at 2 hours predicts DGF while initial resistance predicts one year
      graft survival.

PMID- 22974958
TI  - Extremely marginal liver grafts from deceased donors have outcome similar to
      ideal grafts.
AB  - BACKGROUND: Although there is a worldwide need to expand the donor pool, many
      cadaveric marginal livers are usually discarded for transplantation. Herein, we
      report the outcome of a series of patients receiving marginal grafts. METHODS: We
      analyzed all patients who underwent liver transplantation in our unit from August
      2006 to March 2011 (n = 125) with the use of a prospectively collected database.
      Patients with >=3 of donor (prolonged hypotensive episodes, donor age >55 years,
      high vasopressor drug requirement, hypernatremia, prolonged intensive care unit
      stay, elevated transaminases) and graft-related (cold ischemia >12 hours, warm
      ischemia time >40 minutes and steatosis >30%) extended criteria were defined as
      extremely marginal liver grafts (EMLG). The outcomes of patients receiving EMLG
      were compared with the recipients of grafts without any marginal criteria (ideal
      grafts). RESULTS: The EMLG group (n = 36) showed higher operative transfusion
      requirement (66.6% vs 55.6%) as well as 30-day (11.1% vs 55%) and 1-year (22.2%
      vs 5.5%) mortality rates, compared with the ideal grafts group (n = 18) but
      without a significant difference. Other variables, such as major complications,
      postoperative hemodialysis, ICU and hospital stay, and 1-year survival also were
      not significantly different. CONCLUSIONS: The liver pool can be safely expanded
      using EMLG from deceased donors for liver transplantation. These usually
      discarded liver grafts showed similar early and long-term outcomes compared with
      ideal organs.

PMID- 22974957
TI  - Inhibition of autonomic storm by epidural anesthesia does not influence cardiac
      inflammatory response after brain death in rats.
AB  - BACKGROUND: After brain death (BD) donors usually experience cardiac dysfunction,
      which is responsible for a considerable number of unused organs. Causes of this
      cardiac dysfunction are not fully understood. Some authors argue that autonomic
      storm with severe hemodynamic instability leads to inflammatory activation and
      myocardial dysfunction. OBJECTIVES: To investigate the hypothesis that thoracic
      epidural anesthesia blocks autonomic storm and improves graft condition by
      reducing the inflammatory response. METHODS: Twenty-eight male Wistar rats (250
      350 g) allocated to four groups received saline or bupivacaine via an epidural
      catheter at various times in relation to brain-death induction. Brain death was
      induced by a sudden increase in intracranial pressure by rapid inflation of a
      ballon catheter in the extradural space. Blood gases, electrolytes, and lactate
      analyses were performed at time zero, and 3 and 6 hours. Blood leukocytes were
      counted at 0 and 6 hours. After 6 hours of BD, we performed euthanasia to measure
      vascular adhesion molecule (VCAM)-1, intracellular adhesion molecule (ICAM)-1,
      interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, Bcl-2 and caspase-3 on
      cardiac tissue. RESULTS: Thoracic epidural anesthesia was effective to block the
      autonomic storm with a significant difference in mean arterial pressure between
      the untreated (saline) and the bupivacaine group before BD (P < .05). However, no
      significant difference was observed for the expressions of VCAM-1, ICAM-1, TNF
      alpha, IL-1beta, Bcl-2, and caspase-3 (P > .05). CONCLUSION: Autonomic storm did
      not seem to be responsible for the inflammatory changes associated with BD;
      thoracic epidural anesthesia did not modify the expression of inflammatory
      mediators although it effectively blocked the autonomic storm.

PMID- 22974959
TI  - Predictors of liver donation without kidney recovery in a cohort of expanded
      criteria donors: identifying opportunities to improve expanded criteria donor
      kidney utilization.
AB  - To maximize deceased donation, it is necessary to facilitate organ recovery from
      expanded criteria donors (ECDs). Utilization of donors meeting the kidney
      definition for ECDs increases access to kidney transplantation and reduces
      waiting times; however, ECDs often do not proceed to kidney recovery. Based on a
      prospective study of three Organ Procurement Organizations in the United States,
      we describe the characteristics of donors meeting the Organ Procurement and
      Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60
      years with two of the following: final serum creatinine > 1.5 mg/dL, history of
      hypertension, or death from cerebral vascular accident) who donated a liver
      without kidney recovery. ECDs with organs recovered between February 2003 and
      September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice
      Donor Services were studied (n = 324). All donors were declared dead by
      neurological criteria. Data on a wide range of donor characteristics were
      collected, including donor demographics, medical history, cause of death, donor
      status during hospitalization, serological status, and donor kidney quality.
      Logistic regression models were used to identify donor characteristics predictive
      of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD
      definition for kidneys donated a liver alone (23%). History of diabetes, final
      serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were
      associated with liver-alone donation in univariate models. On multivariate
      analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently
      predictive of liver donation alone. Older age and elevated serum creatinine may
      be perceived as stronger contraindications to kidney donation than the remaining
      elements of the ECD definition. It is likely that at least a proportion of these
      liver-alone donors represent missed opportunities for kidney transplantation.

PMID- 22974960
TI  - Impact of expanded criteria donors on outcomes of recipients after kidney
      transplantation.
AB  - BACKGROUND: Age and comorbidities of brain-dead donors have increased throughout
      the last decade. The use of expanded criteria donors (ECD) has become a common
      clinical practice. The objective of the present study was to compare outcomes of
      patients who underwent kidney transplantation from ECD versus standard criteria
      donors (SCD). METHODS: We studied 1375 adult recipients of kidney
      transplantations from 792 deceased donors in six Quebec centers between 2003 and
      2009. Patient and graft survivals were analyzed using uni- and multivariate
      methods in regard to the effects of donor and recipient characteristics. ECD were
      defined per United Network for Organ Sharing: criteria age >60 years of age or
      age 50 to 59 years with two of three associated risk factors-history of
      cerebrovascular accident, hypertension, or elevated serum creatinine Mean follow
      up was 3.5 +/- 2 years. RESULTS: Among the 792 donors, 510 SCD (64%) and 282 ECD
      (36%) were used for 1375 kidney transplant recipients. ECD had no effect on
      patient (P = .47) or graft (P = .28) survival. Cox proportional hazards
      regression analysis showed female donors (relative risk [RR] 1.75, P = .008),
      recipient age (RR 1.07, P = .0001), and waiting time be for transplantation (RR
      1.000, P = .0001) to be associated with a greater risk of death after
      transplantation. Donor (RR 1.018, P = .0099) and recipient (RR 1.013, P = .0387)
      age and recipient waiting time for transplantation (RR 1.000, P = .0048) were
      also associated with a greater risk of graft loss. CONCLUSION: The use of SCD or
      ECD had no impact on patient or graft survival after kidney transplantation.
      Donor and recipient ages as well as waiting time for transplantation were related
      to graft loss. Waiting time remains a significant factor affecting outcomes;
      efforts should aim to decrease this period.

PMID- 22974961
TI  - Impact of expanded-criteria donors on patient survival after heart, lung, liver
      and combined organ transplantation.
AB  - BACKGROUND: The age and comorbidities of brain-dead donors have increased
      throughout the past decade. The use of expanded-criteria donors (ECDs) has become
      a common clinical practice. The objective of the present study was to compare
      outcomes of patients who underwent heart, lung, liver, and combined organ
      transplantations from expanded- versus standard-criteria donors (SCDs). METHODS:
      We studied 867 adult patients who received deceased-donor organs in 6 Quebec
      centers from 2003 to 2009. Patient survival was analyzed with the use of
      univariate methods with respect to the effect of donor and recipient
      characteristics. ECDs were defined according to United Network for Organ Sharing
      criteria: age >60 years (or 50-59 years with 2 associated risk factors), and
      history of cerebrovascular accident, hypertension, or elevated serum creatinine.
      RESULTS: Among the 664 donors, 438 were SCDs (66%) and 226 ECDs (34%). Two-year
      recipient survival averaged 78 +/- 2% versus 77 +/- 3% in SCD and ECD groups,
      respectively, following liver; 78 +/- 3% versus 74 +/- 10% after lung 87 +/- 3%
      versus 72 +/- 12% following heart, and 75 +/- 9% and 67 +/- 19% after combined
      organ transplantation (P > .05 for all organs). CONCLUSION: The current
      definition of SCD and ECD had no effect on patient survival after lung or liver
      transplantation. There was a trend toward decreased patient survival among heart
      and combined organ transplant recipients of ECDs. Specific donor critieria should
      be defined to quantify donor risk factors for each extrarenal organ.

PMID- 22974962
TI  - Factors associated with patient and graft survival using kidneys from cadaveric
      donors in transplant patients under 18 years of age in Argentina.
AB  - BACKGROUND: Thanks to advances in surgical techniques and immune system
      suppression, the mortality rate in children with end-stage renal disease (ESRD)
      has dramatically declined. Kidney transplantation has become the primary method
      to treat ESRD in the pediatric population. MATERIALS AND METHODS: Information was
      obtained from SINTRA (National Information System of Orrgan Procurement and
      transplantation in Argentina) for the period 1998-2009. We used the Kaplan-Meier
      curve, survival was measured at 30 days, 1, 5, and 10 years. The Cox regression
      variables taken for patient and graft survival were gender and age of both donor
      and recipient, ischemia time (> or <24 hr), etiology of chronic renal failure,
      time on dialysis (> or <3 years) of the recipient, cause of donor's death
      (stroke, head trauma, anoxia, other causes of coma, tumor and others). We coded
      the value of mismatch. For each HLA, it was 0 when they shared the 2. Adding the
      3 types of antigens, the possible mismatch values ranged between 0 and 6.
      However, all had values between 5 and 6. We used SPSS statistical software
      Medcalc 17. RESULTS: We analyzed 345 (54%) men and 290 (46%) women. The average
      age was 12.5 + 3.9 years. The median follow-up time was 4 years (maximum 13
      years). Patient survival rates at 30 days were 99.4%, at 1 year 96.8%, at 5 years
      91.1%, and at 10 years 82.5%. Cox regression for patient survival: being a female
      and receiving HR 1.88 (95% CI 1.09-3.25) P = .023 or donor HR 1.86 (95% CI 1.06
      3.25) P = .030. Tumor HR 17.19 (95% CI 4.48-65.98) P = <.0001. For recipient's
      age compared with <12 years >12 years HR 1.99 (95% CI 1.11-3.65) P = <.024. Graft
      survival rate at 30 days was 97.2%, at 1 year was 91.9%, at 5 years was 79.3% and
      at 10 years was 61.8%. Compared with donor's age <18 years: 45-59 years HR 2.52
      (95% CI 1.42-4.47) P = .002. Glomerulonephritis HR 1.71 (95% CI 1.10-2.77) P =
      .018. Tumor as the cause of donor's death HR 4.39 (95% CI 1.28-2.28) P = .012.
      Time on dialysis > 3 years HR 1.59 (95% CI 1.11-2.28) P = .012. CONCLUSIONS:
      Being a female, receiving a kidney from a woman and tumor as the cause of donor's
      death and age >12 years were associated with worse patient survival. Donor's age
      between 45 and 59, glomerulonephritis as the etiology of renal failure, tumor as
      the cause of death and time on dialysis >3 years were associated with lower graft
      survival.

PMID- 22974963
TI  - Analysis of mortality while on waiting list for kidney transplant in adults in
      Argentina 2005-2009.
AB  - INTRODUCTION: Comparison of survival after renal transplant patients on the
      waiting list is an important factor to evaluate this therapy. OBJECTIVE: To
      measure the magnitude of deceased donor kidney transplant on patient survival
      compared to patients on dialysis and on waiting lists in over 18 years in
      Argentina. MATERIAL AND METHODS: The information was obtained from SINTRA for the
      period January 2003 to December 2009. The follow-up period ended in December
      2010. Survival was considered as the time from the entrance to the waiting list
      until death, the end of the study (June 2009), or last follow-up available,
      whichever came first. The Kaplan-Meir method was used. The survival rate was
      recorded at 30 days, 1, 5 and 10 years. Log-rank was used to compare the curves
      and their statistical significance. The Cox regression model was used to consider
      the variables for both patient and graft survival, such as gender and age, time
      on dialysis, etiology of end-stage renal disease (ESRD), and presence of
      comorbidities. The MedCalc and SPSS 17 statistical packages were used. RESULTS:
      We analyzed 1682 patients transplanted average age 48.14 + 13.48 years and 3647
      patients on waiting lists average age 47.88 + 14.32 years. For patients
      transplanted 30-day survival was 99.8% at 1 year 96.2% and 5 years of 79.9%. For
      patients on the waiting list survival at 30 days was 99.7% at 1 year and 5 years
      94.6% 66.6%. Chi-square was 42.77, P = <.0001. HR 0.64 (95% CI 0.56 to 0.73). Cox
      regression for patients on waiting lists HR 1.40 (95% CI 1.20-1.63) P = <.0001.
      The time dependent Cox regression showed for patients transplanted at 30 days, <1
      year >1 year showed HR 4.18 (95% CI 2.88-6.06) P = <.0001, HR 0.40 (95% CI 0.27
      to 0.61) P = <.0001 and HR 0.19 (95% CI 1.12-0.29) P = <.0001, respectively.
      CONCLUSIONS: Survival, both at baseline and in the long term, is better in
      transplant patients as compared to patients on waiting list. In Cox time
      dependant regression the risk of death during the first 30 days is 4 times higher
      in transplant patients. This reverses and at 1 year, transplant patients are 60%
      less likely to die, and after one year this probability is 81% lower (P =<.0001).

PMID- 22974964
TI  - Factors associated with patient and graft survival using kidneys from cadaveric
      donors in transplanted patients over 18 years of age in Argentina.
AB  - BACKGROUND: With improvements in short-term kidney graft and patient survival,
      focus has shifted to understand patient and graft features that affect long-term
      survival. MATERIALS AND METHODS: This retrospective analysis from January 1998 to
      December 2009 employed Kaplan-Meier analysis to evaluate survival ratios at 30
      days as well as 1, 5, and 10 years. A multivariable Cox regression model
      considered variables of donor and recipient, gender and age, cold ischemia time
      (CIT), chronic renal failure etiology, time on dialysis (TD) and cause of donor
      death. The mismatch (MM) value was coded according to the number of antigens
      shared by both the donor and the recipient for HLA-A, B, and DR. The MM values
      ranged between 0 and 6. Two groups were analyzed according the number of shared
      antigens: 0 to 3 versus 4 to 6. RESULTS: Among 3030 (55.85%) males and 2395
      (44.15%) females, the overall mean age was 46.9 +/- 13.9 years. Median follow-up
      was 4 years (max 13 years). Patient survival rate (SR) was 97.5% at 30 days,
      87.5% at 1 year, 74.5% at 5 years, and 59.2% at 10 years. Using Cox analysis,
      patient SR was affected by: diabetic nephropathy (DN) hazard ratio (HR) 1.55 (95%
      confidence interval [CI 95%] 1.21-1.97) P = .0005; head trauma (HT) cause of
      donor death HR 0.83 (0.73-0.95) P = .0005 and donor age (DA) compared by 18 to 44
      years: 45 to 59 years HR 1.44 (CI95% 1.00-1.30) P = .043, >60 years HR 1.41
      (CI95% 1.17-1.70) P = .0004. In addition relevant factors were recipient age (RA)
      compared by 18 to 44 years: 45 to 59 HR 1.99 (CI95% 1.74-2.27) P < .0001, >60
      years HR 3.24 (CI95% 2.79-3.75) P < .0001 and DT >7 years HR 1.33 (CI95% 1.19
      1.48) P = .0001. MM HLA 0 to 3 level HR 0.78 (CI95% 0.69-0.88) P < .0001. Graft
      SR was 95% at 30 days, 81.6% at 1 year, 64.7% at 5 years, and 47.3% at 10 years.
      The relevant factors were: DN HR 1.26 (CI95% 1.01-1.57) P = .04; HT HR 0.82 (0.74
      0.91) P = .0004; DA compared by 18 to 44 years: 45-59 years HR 1.19 (CI95% 1.07
      1.32) P = .002, >60 years HR 1.53 (CI95% 1.30-1.80) P < .0001; RA compared by 18
      to 44 years: 45-59 HR 1.33 (CI95% 1.19-1.47) P < .0001, >60 years HR 1.84 (CI95%
      1.63-2.09) P < .0001; DT > 7 years HR 1.22 (CI95% 1.11-1.35) P = .0001; CIT >24
      hours HR 1.13 (CI95% 1.03-1.23) P = .009 and MM HLA 0 to 3 HR 0.82 (CI95% 0.74
      0.91) P = .0002. CONCLUSION: HT as the cause of donor death and MM between 0 and
      3 were associated with better patient and graft SR, DN, TD over 7 years, DA and
      RA over 45 were associated with lower patient SR. CIT > 24 hours, DN, TD over 7
      years, as well as donor and recipient ages over 45 yr were associated with a
      lower graft SR.

PMID- 22974966
TI  - Risk factors in cadaveric donors of livers procured for elective and urgent
      recipients.
AB  - Use of livers from cadaveric nonstandard donors has become justified, especially
      for recipients awaiting urgent transplantations. However, it is known that
      results are superior when organs are obtained from ideal rather than expanded
      criteria donors. We designed a study to compare the characteristics of 582 liver
      donors whose organs were used for elective versus urgent transplantations in 2006
      2008 and the recipients' outcomes. Donors and recipients were classified into 2
      groups: 1) elective (n = 387); and 2) urgent transplantations (n = 195). We
      evaluated 12 donor risk factors: age >55 years, alcohol ingestion, intensive care
      unit stay >4 days, hypotensive episodes (<70 mm Hg >10 min), noradrenaline dose
      >0.1 MUg/kg/min, anti-hepatitis B of core (+), Na level >155 mmol/L,
      international normalized ratio >1.5, aspartate transaminase >140 U/L, alanine
      transaminase >170 U/L, bilirubin >2.0 mg/dL, and changes in liver sonography.
      There were no significant differences in the frequency of incidence of 11 donor
      risk factors in both groups. Only sodium level >155 mEq/L significantly (P = .04)
      differed. Donors for elective recipients showed this factor more frequently than
      the urgent cohort. The mean number of risk factors per donor among the elective
      cases was 2.28 and for the urgent cases 2.3, a difference that was not
      significant. In almost all cases of liver transplantations (94%), donor-related
      risk factors were acceptable. The criteria for cadaveric liver donors were not
      different for elective versus urgent recipients; biologic characteristics of the
      transplanted organs were similar in both groups. A tendency was not observed to
      expand donor criteria for urgent recipients.

PMID- 22974965
TI  - Living donor psychosocial assesment/follow-up practices in the partners'
      countries of the ELIPSY project.
AB  - BACKGROUND: Living donor (LD) transplantation has increased recently, but
      psychosocial aspects of living donation have not been well characterized, as risk
      factors for the donors. ELIPSY is a project confunded by EAHC, seeking to develop
      a common methodology for all EU countries for LD assessment/follow-up in the
      psychosocial sphere (www.eulivingdonor.eu). OBJECTIVE: To evaluate current
      psychosocial LD assessment/follow-up practices among European centers for key
      aspects and differences between kidney and liver programs. METHODS: Within a
      timeline of 30 months, this phase of the project sought to identify current LD
      psychosocial assessment/follow-up practices. The final survey concerned two
      versions focused on the kidney and on liver transplant program. The survey took
      place in ELIPSY partner centers under their own responsibility. Each of the
      centers sent the survey to other ones performing LD in their country. Partners in
      the EULID project includes ones in the United Kingdom, Poland, and Romania. The
      results were analyzed separately for each program seeking to compare and define
      differences among them. RESULTS: The survey took place in 10 European countries
      including 65 centers with LD programs. Positive answers regarding psychosocial
      assessment/follow-up practices were obtained for 26 (42%) kidney and nine (38%)
      liver centers. Some centers perform several psychosocial follow-ups but did not
      explain their tools, whereas the centers that did explain the tools used the same
      ones for both programs.

PMID- 22974967
TI  - Biochemical, histopathological and clinical evaluation of delayed effects caused
      by methamidophos isoforms and TOCP in hens: ameliorative effects using control of
      calcium homeostasis.
AB  - This work evaluated the potential of the isoforms of methamidophos to cause
      organophosphorus-induced delayed neuropathy (OPIDN) in hens. In addition to
      inhibition of neuropathy target esterase (NTE) and acetylcholinesterase (AChE),
      calpain activation, spinal cord lesions and clinical signs were assessed. The
      isoforms (+)-, (+/-)- and (-)-methamidophos were administered at 50mg/kg orally;
      tri-ortho-cresyl phosphate (TOCP) was administered (500mg/kg, po) as positive
      control for delayed neuropathy. The TOCP hens showed greater than 80% and
      approximately 20% inhibition of NTE and AChE in hen brain, respectively. Among
      the isoforms of methamidophos, only the (+)-methamidophos was capable of
      inhibiting NTE activity (approximately 60%) with statistically significant
      difference compared to the control group. Calpain activity in brain increased by
      40% in TOCP hens compared to the control group when measured 24h after dosing and
      remained high (18% over control) 21 days after dosing. Hens that received (+)
      methamidophos had calpain activity 12% greater than controls. The
      histopathological findings and clinical signs corroborated the biochemical
      results that indicated the potential of the (+)-methamidophos to be the isoform
      responsible for OPIDN induction. Protection against OPIDN was examined using a
      treatment of 2 doses of nimodipine (1mg/kg, i.m.) and one dose of calcium
      gluconate (5mg/kg, i.v.). The treatment decreased the effect of OPIDN-inducing
      TOCP and (+)-methamidophos on calpain activity, spinal cord lesions and clinical
      signs.

PMID- 22974969
TI  - Synthesis, ESR, UV-Visible and reactivity studies of new bis(N-dimethoxyaniline
      3,5-(t)Bu2-salicylaldiminato)copper(II) complexes.
AB  - Several new copper(II) complexes (4-6) with N-dimethoxyphenyl-3,5-(t)Bu(2)
      salicylaldimine ligands abbreviated as N-R-3,5-DTBS, where R=2,4-dimethoxyphenyl
      (1), 2,5-dimethoxyphenyl (2) and 3,5-dimethoxyphenyl (3) have been prepared and
      their spectroscopic (IR, (1)H NMR, UV/Vis, ESR), magnetic and redox reactivity
      are described. The ESR spectra of frozen-solution 4-6 and solid state 4 and 5 are
      indicative of axially symmetric g-tensor (g([parallel])>g([perpendicular])>2.03).
      The powder ESR spectrum of 6 is unusual for CuN(2)O(2) type systems and exhibits
      "reversed" type (g([parallel])<g([perpendicular])) signal with a rhombic g-tensor
      g(3) (2.235)>g(2) (2.128)>g(1) (2.019) pattern indicative of a d(z)(2) ground
      state. Chemical oxidation of 4 and 6, as supported by ESR and UV/Vis techniques,
      generates new Cu(II) species and Cu(II)-phenoxyl radicals. The CV studies have
      shown that the complexes possess ligand-centered and copper(II)-centered quasi
      reversible and irreversible responses.

PMID- 22974970
TI  - Avascular tumour growth dynamics and the constraints of protein binding for drug
      transportation.
AB  - The potential for the use of in-silico models of disease in progression
      monitoring is becoming increasingly recognised, as well as its contribution to
      the development of complete curative processes. In this paper we report the
      development of a hybrid cellular automaton model to mimic the growth of avascular
      tumours, including the infusion of a bioreductive drug to study the effects of
      protein binding on drug transportation. The growth model is operated within an
      extracellular tumour microenvironment. An artificial Neural Network based scheme
      was implemented that modelled the behaviours of each cell (proliferation,
      quiescence, apoptosis and/or movement) based on the complex heterogeneous
      microenvironment; consisting of oxygen, glucose, hydrogen ions, inhibitory
      factors and growth factors. To validate the growth model results, we conducted
      experiments with multicellular tumour spheroids. These results showed good
      agreement with the predicted growth dynamics. The outcome of the avascular tumour
      growth model suggested that tumour microenvironments have a strong impact on cell
      behaviour. To address the problem of cellular proteins acting as resistive
      factors preventing efficient drug penetration, a bioreactive drug (tirapazamine)
      was added to the system. This allowed us to study the drug penetration through
      multicellular layers of tissue after its binding to cellular proteins. The
      results of the in vitro model suggested that the proteins reduce the toxicity of
      the drug, reducing its efficacy for the most severely hypoxic fractions furthest
      from a functional blood vessel. Finally this research provides a unique
      comparison of in vitro tumour growth with an intelligent in silico model to
      measure bioreductive drug availability inside tumour tissue through a set of
      experiments.

PMID- 22974968
TI  - The effects of sex, metabolic syndrome and exercise on postprandial lipemia.
AB  - OBJECTIVE: Exercise has been suggested to have cardioprotective benefits due to a
      lowering of postprandial triglycerides (PPTG). We hypothesized that a morning
      exercise bout would significantly lower PPTG measured over a full day, in
      response to moderate fat meals (35% energy) in men more so than women, and in
      metabolic syndrome (MetS) relative to normal weight (NW) individuals.
      MATERIALS/METHODS: Participants completed two randomized study days; one control
      and one exercise day (60 min of morning exercise, 60% VO(2peak)). Meals were
      consumed at breakfast, lunch and dinner with the energy expended during exercise
      replaced on the active day. The areas (AUC) and incremental areas (IAUC) under
      the curve were calculated for total triglycerides, total cholesterol and other
      metabolites. RESULTS: Exercise did not significantly change the PPTG AUC & IAUC
      overall, or within, or between, each sex or group (NW and MetS). Exercise induced
      a 30% decrease in total cholesterol IAUC (p=0.003) in NW subjects. Overall, women
      had a lower IAUC for PPTG compared to men (p=0.037), with the greatest difference
      between MetS women and MetS men, due to a sustained drop in TG after lunch in the
      women. This suggests that PP, rather than fasting, lipid analyses may be
      particularly important when evaluating sex differences in metabolic risk.
      CONCLUSIONS: With energy replacement, moderate morning exercise did not result in
      a significant decrease in PPTG excursions. Exercise did elicit a significant
      decrease in PP cholesterol levels in NW subjects, suggesting a potential
      mechanism for the cardioprotective effects of exercise.

PMID- 22974971
TI  - Negative plant soil feedback explaining ring formation in clonal plants.
AB  - Ring shaped patches of clonal plants have been reported in different
      environments, but the mechanisms underlying such pattern formation are still
      poorly explained. Water depletion in the inner tussocks zone has been proposed as
      a possible cause, although ring patterns have been also observed in ecosystems
      without limiting water conditions. In this work, a spatially explicit model is
      presented in order to investigate the role of negative plant-soil feedback as an
      additional explanation for ring formation. The model describes the dynamics of
      the plant biomass in the presence of toxicity produced by the decomposition of
      accumulated litter in the soil. Our model qualitatively reproduces the emergence
      of ring patterns of a single clonal plant species during colonisation of a bare
      substrate. The model admits two homogeneous stationary solutions representing
      bare soil and uniform vegetation cover which depend only on the ratio between the
      biomass death and growth rates. Moreover, differently from other plant spatial
      patterns models, but in agreement with real field observations of vegetation
      dynamics, we demonstrated that the pattern dynamics always lead to spatially
      homogeneous vegetation covers without creation of stable Turing patterns.
      Analytical results show that ring formation is a function of two main components,
      the plant specific susceptibility to toxic compounds released in the soil by the
      accumulated litter and the decay rate of these same compounds, depending on
      environmental conditions. These components act at the same time and their
      respective intensities can give rise to the different ring structures observed in
      nature, ranging from slight reductions of biomass in patch centres, to the
      appearance of marked rings with bare inner zones, as well as the occurrence of
      ephemeral waves of plant cover. Our results highlight the potential role of plant
      soil negative feedback depending on decomposition processes for the development
      of transient vegetation patterns.

PMID- 22974972
TI  - Green tomato extract attenuates high-fat-diet-induced obesity through activation
      of the AMPK pathway in C57BL/6 mice.
AB  - Obesity is a risk factor for numerous metabolic disorders. Recently, natural
      compounds that may be beneficial for improving obesity have received increasing
      attention. In this study, we investigated whether red and green tomato extracts
      attenuate high-fat-diet-induced obesity in C57BL/6 mice. The mice were maintained
      on a normal diet (ND) or high-fat diet (HFD) for 4 weeks and then fed ND, HFD,
      HFD plus 2% red tomato extract (RTE) or HFD plus 2% green tomato extract (GTE)
      for 13 weeks. The weekly food intakes among the groups were not significantly
      different. Body weight of mice fed HFD plus GTE was significantly decreased to
      the level of mice fed ND, but the body weight was only slightly reduced in mice
      fed HFD plus RTE. Epididymal adipose tissue and liver weights were significantly
      decreased in mice fed HFD plus GTE compared to those in HFD. Serum total
      cholesterol and low-density lipoprotein cholesterol levels in mice fed GTE were
      modestly reduced, and liver total cholesterol level was strongly decreased in HFD
      plus GTE-fed mice compared to that in HFD-fed mice. Adenosine-monophosphate
      activated protein kinase (AMPK) and acetyl-CoA carboxylase phosphorylation in
      liver from HFD plus GTE-fed mice was significantly elevated, and HMG-CoA
      reductase expression was also significantly decreased. GTE strongly decreased the
      expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer
      binding protein alpha and perilipin in the adipose tissue of mice fed HFD plus
      GTE. Our results indicate that the antiobesity effects of GTE may be associated
      with activation of the AMPK pathway.

PMID- 22974973
TI  - Metabolic response to green tea extract during rest and moderate-intensity
      exercise.
AB  - BACKGROUND: Green tea catechins have been hypothesized to increase energy
      expenditure and fat oxidation by inhibiting catechol-O-methyltransferase (COMT)
      and thus promoting more sustained adrenergic stimulation. Metabolomics may help
      to clarify the mechanisms underlying their putative physiological effects.
      OBJECTIVE: The study investigated the effects of 7-day ingestion of green tea
      extract (GTE) on the plasma metabolite profile at rest and during exercise.
      METHODS: In a placebo-controlled, double-blind, randomized, parallel study, 27
      healthy physically active males consumed either GTE (n=13, 1200 mg catechins, 240
      mg caffeine/day) or placebo (n=14, PLA) drinks for 7 days. After consuming a
      final drink (day 8), they rested for 2 h and then completed 60 min of moderate
      intensity cycling exercise (56% +/- 4% VO(2)max). Blood samples were collected
      before and during exercise. Plasma was analyzed using untargeted four-phase
      metabolite profiling and targeted profiling of catecholamines. RESULTS: Using the
      metabolomic approach, we observed that GTE did not enhance adrenergic stimulation
      (adrenaline and noradrenaline) during rest or exercise. At rest, GTE led to
      changes in metabolite concentrations related to fat metabolism (3-beta
      hydroxybutyrate), lipolysis (glycerol) and tricarboxylic acid cycle (TCA) cycle
      intermediates (citrate) when compared to PLA. GTE during exercise caused
      reductions in 3-beta-hydroxybutyrate concentrations as well as increases in
      pyruvate, lactate and alanine concentrations when compared to PLA. CONCLUSIONS:
      GTE supplementation resulted in marked metabolic differences during rest and
      exercise. Yet these metabolic differences were not related to the adrenergic
      system, which questions the in vivo relevance of the COMT inhibition mechanism of
      action for GTE.

PMID- 22974974
TI  - The cortical dynamics underlying effective switching of auditory spatial
      attention.
AB  - Successful rapid deployment of attention to relevant sensory stimuli is critical
      for survival. In a complex environment, attention can be captured by salient
      events or be deployed volitionally. Furthermore, when multiple events are of
      interest concurrently, effective interaction with one's surroundings hinges on
      efficient top-down control of shifting attention. It has been hypothesized that
      two separate cortical networks coordinate attention shifts across multiple
      modalities. However, the cortical dynamics of these networks and their behavioral
      relevance to switching of auditory attention are unknown. Here we show that the
      strength of each subject's right temporoparietal junction (RTPJ, part of the
      ventral network) activation was highly correlated with their behavioral
      performance in an auditory task. We also provide evidence that the recruitment of
      the RTPJ likely precedes the right frontal eye fields (FEF; participating in both
      the dorsal and ventral networks) and middle frontal gyrus (MFG) by around 100 ms
      when subjects switch their auditory spatial attention.

PMID- 22974975
TI  - Fat-free body mass but not fat mass is associated with reduced gray matter volume
      of cortical brain regions implicated in autonomic and homeostatic regulation.
AB  - Obesity has been associated with alterations of both functional and structural
      aspects of the human central nervous system. In obese individuals both fat mass
      (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non
      adipose tissues) are increased and it remains unknown whether these compartments
      have separate effects on human brain morphology. We used voxel-based morphometry
      to investigate the relationships between measures of body composition and
      regional gray matter volume (GMV) in 76 healthy adults with a wide range of
      adiposity (24 F/52 M; age 32.1 +/- 8.8 years; percentage of body fat [PFAT%] 25.5
      +/- 10.9%; BMI 29.8 +/- 8.9). Fat-free mass index (FFMI kg * m(-2)) showed
      negative associations in bilateral temporal regions, the bilateral medial and
      caudolateral OFC, and the left insula. Fat mass index (FMI kg * m(-2)) showed
      similar, but less extensive negative associations within temporal cortical
      regions and the left caudolateral orbitofrontal cortex (OFC). In addition,
      negative associations were seen for FMI with GMV of the cerebellum. Associations
      of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of
      adiposity. No associations were seen between measures of adiposity (i.e. FM and
      PFAT) and GMV when adjusted for FFM. The majority of regions that we find
      associated with FFM have been implicated in the regulation of eating behavior and
      show extensive projections to central autonomic and homeostatic core structures.
      These data indicate that not adipose tissue or relative adiposity itself, but
      obesity related increases in absolute tissue mass and particularly FFM may have a
      more predominant effect on the human brain. This might be explained by the high
      metabolic demand of FFM and related increases in total energy needs.

PMID- 22974976
TI  - Neuroimaging in aphasia treatment research: issues of experimental design for
      relating cognitive to neural changes.
AB  - The design of functional neuroimaging studies investigating the neural changes
      that support treatment-based recovery of targeted language functions in acquired
      aphasia faces a number of challenges. In this paper, we discuss these challenges
      and focus on experimental tasks and experimental designs that can be used to
      address the challenges, facilitate the interpretation of results and promote
      integration of findings across studies.

PMID- 22974977
TI  - Nitrosative stress mediated misfolded protein aggregation mitigated by Na-D-beta
      hydroxybutyrate intervention.
AB  - Mitochondrial dysfunction, leading to elevated levels of reactive oxygen species,
      is associated with the pathogenesis of neurodegenerative disorders. Rotenone, a
      mitochondrial stressor induces caspase-9 and caspase-3 activation leading
      proteolytic cleavage of substrate nuclear poly(ADP-ribose) polymerase (PARP).
      PARP cleavage is directly related to apoptotic cell death. In this study, we have
      monitored the aggregation of green-fluorescent protein (GFP)-tagged synphilin-1,
      as a rotenone-induced Parkinsonia-onset biomarker. We report that the innate
      ketone body, Na-D-beta-hydroxybutyrate (NabetaHB) reduces markedly the incidence
      of synphilin-1 aggregation. Furthermore, our data reveal that the metabolic
      byproduct also prevents rotenone-induced caspase-activated apoptotic cell death
      in dopaminergic SH-SY5Y cells. Together, these results suggest that NabetaHB is
      neuroprotective; it attenuates effects originating from mitochondrial insult and
      can serve as a scaffold for the design and development of sporadic neuropathies.

PMID- 22974978
TI  - Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a
      crucial role for Girdin in the nestin lineage.
AB  - Girdin is an Akt substrate and actin-binding protein. Mice with germ-line
      deletions of Girdin (a non-conditional knockout, (ncKO)) exhibit complete
      postnatal lethality accompanied by growth retardation and neuronal cell migration
      defects, which results in hypoplasia of the olfactory bulb and granule cell
      dispersion in the dentate gyrus. However, the physiological and molecular
      abnormalities in Girdin ncKO mice are not fully understood. In this study, we
      first defined the distribution of Girdin in neonates (P1) and adults (6months or
      older) using beta-galactosidase activity in tissues from ncKO mice. The results
      indicate that Girdin is expressed throughout the nervous system (brain, spinal
      cord, enteric and autonomic nervous systems). In addition, beta-galactosidase
      activity was detected in non-neural tissues, particularly in tissues with high
      tensile force, such as tendons, heart valves, and skeletal muscle. In order to
      identify the cellular population where the Girdin ncKO phenotype originates,
      newly generated Girdin flox mice were crossed with nestin promoter-driven Cre
      transgenic mice to obtain Girdin conditional knockout (cKO) mice. The phenotype
      of Girdin cKO mice was almost identical to ncKO mice, including postnatal
      lethality, growth retardation and decreased neuronal migration. Our findings
      indicate that loss of Girdin in the nestin cell lineage underlies the phenotype
      of Girdin ncKO mice.

PMID- 22974979
TI  - Modulation of membrane rigidity by the human vesicle trafficking proteins Sar1A
      and Sar1B.
AB  - The sculpting of membranes into highly curved vesicles is central to
      intracellular cargo trafficking, yet the mechanical activities of trafficking
      proteins remain poorly understood. Using an optical trap based assay that
      measures in vitro membrane response to imposed deformations, we examined the
      behavior of the two human paralogs of Sar1, a key component of the COPII family
      of vesicle coat proteins. Like their yeast counterpart, the human Sar1 proteins
      can lower the mechanical rigidity of the membranes to which they bind. Unlike the
      yeast Sar1, the rigidity is not a monotonically decreasing function of
      concentration. At high concentrations, we find increased bending rigidity and
      decreased protein mobility. These features imply a model in which protein
      clustering governs membrane mechanical properties.

PMID- 22974980
TI  - PKCdelta promotes etoposide-induced cell death by phosphorylating Hsp27 in HeLa
      cells.
AB  - We investigated the regulation of Hsp27 phosphorylation by protein kinase C delta
      (PKCdelta) during etoposide-induced apoptosis. The phosphorylation of Hsp27 at
      Ser78 was temporally correlated with the proteolytic activation of PKCdelta
      during apoptosis. Hsp27 phosphorylation was dependent on the activity of PKCdelta
      since treatment with rottlerin, a chemical inhibitor of PKCdelta, or
      overexpression of a PKCdelta dominant negative mutant abolished the
      phosphorylation. In addition, recombinant PKCdelta phosphorylated Hsp27 at Ser78
      in vitro. Moreover, caspase-3 was specifically activated following Hsp27
      phosphorylation at Ser78. Pull-down assays using a phosphomimetic Hsp27 mutant
      revealed that binding between Hsp27 and cytochrome c was abolished by the
      phosphorylation. These results suggest that Hsp27 dissociates from cytochrome c
      following PKCdelta-mediated phosphorylation at Ser78, which allows formation of
      the apoptosome and stimulates apoptotic progression.

PMID- 22974981
TI  - Selenate inhibits adipogenesis through induction of transforming growth factor
      beta1 (TGF-beta1) signaling.
AB  - Selenium is essential for many aspects of human health. While selenium is known
      to protect against cancer and cardiovascular diseases, the role of selenium in
      adipose development is unknown. Here we show that selenate at non-toxic
      concentration exhibits an anti-adipogenic function in vitro and ex vivo. In
      addition, selenate induced a morphological change of these cells from fibroblast
      like to spindle cell shape. However, other forms of selenium, including selenite
      and methylseleninic acid, showed either toxic or no effect on adipogenesis and
      morphology change of preadipocytes. The effects of selenate on adipogenesis and
      cell morphology change were blunted by the treatment with SB431542, a specific
      inhibitor of transforming growth factor-beta1 (TGF-beta1) receptor,
      neutralization TGF-beta1 by its antibody, and knockdown of TGF-beta1 in
      preadipocytes, suggesting a requirement of TGF-beta signaling for the anti
      adipogenic function of selenate. Among tested forms of selenium, selenate appears
      to be an effective activator of TGF-beta1 expression in preadipocytes. These
      results indicate that selenate is a novel dietary micromineral that activates TGF
      beta1 signaling in preadipocytes and modulates adipogenesis.

PMID- 22974982
TI  - G-ruption: the third international meeting on G-quadruplex and G-assembly.
AB  - A three and a half day conference focusing on nucleic acid structures called G
      quadruplexes (G4s) and other guanine-based assemblies was held in Sorrento, Italy
      (June 28-July 1, 2011) and featured 35 invited talks and over 89 posters. The G
      quadruplex field continues to expand at an explosive rate with the emergence of
      new connections to biology, chemistry, physics, and nanotechnology. Following the
      trend established by the previous two international G4 meetings, the conference
      touched upon all these areas and facilitated productive exchanges of ideas
      between researchers from all over the world.

PMID- 22974984
TI  - Quantitative analysis of the mechanism of DNA binding by Bacillus DnaA protein.
AB  - DnaA protein has the sole responsibility of initiating a new round of DNA
      replication in prokaryotic organisms. It recognizes the origin of DNA
      replication, and initiates chromosomal DNA replication in the bacterial genome.
      In Gram-negative Escherichia coli, a large number of DnaA molecules bind to
      specific DNA sequences (known as DnaA boxes) in the origin of DNA replication,
      oriC, leading to the activation of the origin. We have cloned, expressed, and
      purified full-length DnaA protein in large quantity from Gram-positive pathogen
      Bacillus anthracis (DnaA(BA)). DnaA(BA) was a highly soluble monomeric protein
      making it amenable to quantitative analysis of its origin recognition mechanisms.
      DnaA(BA) bound DnaA boxes with widely divergent affinities in sequence and ATP
      dependent manner. In the presence of ATP, the K(D) ranged from 3.8 * 10(-8) M for
      a specific DnaA box sequence to 4.1 * 10(-7) M for a non-specific DNA sequence
      and decreased significantly in the presence of ADP. Thermodynamic analyses of
      temperature and salt dependence of DNA binding indicated that hydrophobic
      (entropic) and ionic bonds contributed to the DnaA(BA).DNA complex formation.
      DnaA(BA) had a DNA-dependent ATPase activity. DNA sequences acted as positive
      effectors and modulated the rate (V(max)) of ATP hydrolysis without any
      significant change in ATP binding affinity.

PMID- 22974983
TI  - Alterations in brush border membrane enzymes, carbohydrate metabolism and
      oxidative damage to rat intestine by potassium bromate.
AB  - The acute toxicity of potassium bromate (KBrO(3)) on rat small intestine was
      studied in this work. Animals were given a single oral dose of KBrO(3) (100 mg/kg
      body weight) and sacrificed 12, 24, 48, 96 and 168 h after the treatment; control
      animals were not given KBrO(3). The administration of KBrO(3) resulted in a
      reversible decline in the specific activities of several BBM enzymes. Lipid
      peroxidation, protein oxidation and hydrogen peroxide levels increased while
      total sulfhydryl groups and reduced glutathione decreased in KBrO(3)-treated rats
      indicating induction of oxidative stress in the intestinal mucosa. The activities
      of anti-oxidant and carbohydrate metabolic enzymes were also altered upon KBrO(3)
      treatment. The maximum changes in all the parameters were 48 h after
      administration of KBrO(3) after which recovery took place, in many cases almost
      to control values after 168 h. Histopathological studies supported the
      biochemical findings showing extensive damage to the intestine at 48 h and
      recovery at 168 h. These results show that a single oral dose of KBrO(3) causes
      reversible oxidative damage to the intestine.

PMID- 22974985
TI  - Formulation and delivery of improved amorphous fenofibrate solid dispersions
      prepared by thin film freezing.
AB  - The objective of this study was to prepare amorphous fenofibrate (FB) solid
      dispersions using thin film freezing (TFF) and to incorporate the solid
      dispersions into pharmaceutically acceptable dosage forms. FB solid dispersions
      prepared with optimized drug/polymer ratios were characterized by modulated
      differential scanning calorimetry (MDSC), powder X-ray diffraction (XRD),
      scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface
      area measurements, Fourier-transform infrared spectroscopy-attenuated total
      reflectance (FTIR-ATR), and supersaturation dissolution testing. Furthermore, a
      dry granulation technique was used to encapsulate the TFF compositions for in
      vitro dissolution and in vivo animal pharmacokinetic studies. The results showed
      that the TFF process produced amorphous, porous, microstructured, and stable
      solid dispersions with high surface areas. Development of solid oral dosage forms
      revealed that the performance of the FB containing solid dispersions was not
      affected by the formulation process, which was confirmed by DSC and XRD.
      Moreover, an in vivo pharmacokinetic study in rats revealed a significant
      increase in FB absorption compared to bulk FB. We confirmed that amorphous solid
      dispersions with large surface areas produced by the TFF process displayed
      superior dissolution rates and corresponding enhanced bioavailability of the
      poorly water-soluble drug, FB.

PMID- 22974987
TI  - Caecilians.

PMID- 22974986
TI  - Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations:
      stability studies and in vivo efficacy.
AB  - Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid
      (IPAA), are often used in dermocosmetic products due to their higher stability
      than vitamin C free form as well as its proposed effects in skin; however, there
      are no studies analyzing IPAA stability or its in vivo effects when present in
      dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability
      and pre-clinical and clinical efficacy of dermocosmetic formulations containing
      IPAA in skin hydration and microrelief. Chemical stability of the formulations
      added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre
      clinical evaluation, experimental formulations were topically applied on hairless
      skin mice during 5 days and animal skins were analyzed by non-invasive biophysic
      techniques (water content of stratum corneum, TEWL, viscoelasticity, and
      microrelief) and by histopathological studies. For clinical efficacy tests, the
      formulations were topically applied to the forearm and face of human volunteers,
      and 3h and 15 days after applications, the skins were evaluated by the same non
      invasive techniques mentioned before. Results showed that formulations containing
      IPAA had medium stability and had pronounced moisturizing effects on stratum
      corneum and on viable epidermis. These formulations also improved skin
      microrelief especially in relation to skin smoothness and roughness.

PMID- 22974988
TI  - Automated mapping of social networks in wild birds.

PMID- 22974989
TI  - Wingless virgin queens assume helper roles in Acromyrmex leaf-cutting ants.

PMID- 22974991
TI  - Global distribution of a wild alga revealed by targeted metagenomics.

PMID- 22974990
TI  - The first World Cell Race.

PMID- 22974992
TI  - Laminopathies: too much SUN is a bad thing.
AB  - SUN proteins accelerate the pathological progression of laminopathies. Although
      the mechanisms remain to be elucidated, an intriguing possibility is that high
      levels of SUN proteins lead to a hyperactive DNA damage response.

PMID- 22974993
TI  - Pollination: the price of attraction.
AB  - Nectar is the major currency bringing together plants and pollinators; yet the
      costs and benefits of nectar production remain poorly understood. A low nectar
      line developed in Petunia offers an innovative approach to this problem and may
      offer clues to why some plants cheat and secure pollination via deception.

PMID- 22974994
TI  - Algal biogeography: metagenomics shows distribution of a picoplanktonic
      pelagophyte.
AB  - How can we determine the distribution of uncultured marine microorganisms?
      Targeted metagenomics has provided the complete chloroplast genome sequence, and
      the distribution, for a picoplanktonic pelagophyte alga.

PMID- 22974995
TI  - Human behaviour: sex ratio and the city.
AB  - The ratio of males to females in a population is known to influence the
      behaviour, life histories and demography of animals. A recent experimental study
      finds that sex ratio also affects human economic behaviour, and in a manner
      consistent with evolutionary theory.

PMID- 22974996
TI  - Protein evolution: when two become three.
AB  - Bacterial signaling pathways provide wonderful systems for analyzing protein
      evolution in vivo. A systematic dissection of the phosphate-sensing machinery in
      proteobacteria shows that adaptive, not neutral, mutations disable deleterious
      crosstalk with closely related signaling systems.

PMID- 22974997
TI  - Plant actin: trying to connect you.
AB  - How do plant actin filaments attach to membranes? Recent studies reveal the
      presence of plant-specific connectors.

PMID- 22974999
TI  - Cell adhesion: a FERM grasp of the tail sorts out integrins.
AB  - As well as modulating integrin activation, a conserved NPxY motif in integrin
      cytoplasmic tails that binds the FERM-domain-containing proteins kindlin and
      sorting nexin 17 plays pivotal roles in integrin recycling and degradation.

PMID- 22975000
TI  - The evolutionary psychology of healing: a human success story.

PMID- 22974998
TI  - Organelle signaling: how stressed chloroplasts communicate with the nucleus.
AB  - Plastids are able to relay information to the nucleus to regulate stress
      responses. A new genetic screen has identified an isoprenoid intermediate that
      accumulates in stressed plastids and acts as a novel retrograde signal.

PMID- 22975001
TI  - Studies on Aplysia neurons suggest treatments for chronic human disorders.
AB  - For decades, the marine snail Aplysia has proven to be a powerful system for
      analyzing basic neurobiological mechanisms, particularly cellular and molecular
      mechanisms of neural plasticity. Three new findings on Aplysia may be relevant
      for the understanding and treatment of chronic human disorders. This research on
      this simple molluscan nervous system may lead to new therapeutic approaches for
      spinal cord injury, Fragile X syndrome, and genetic learning deficits more
      generally.

PMID- 22975002
TI  - The evolutionary origins of mood and its disorders.
AB  - The term 'mood' in its scientific usage refers to relatively enduring affective
      states that arise when negative or positive experience in one context or time
      period alters the individual's threshold for responding to potentially negative
      or positive events in subsequent contexts or time periods. The capacity for mood
      appears to be phylogenetically widespread and the mechanisms underlying it are
      highly conserved in diverse animals, suggesting it has an important adaptive
      function. In this review, we discuss how moods can be classified across species,
      and what the selective advantages of the capacity for mood are. Core moods can be
      localised within a two-dimensional continuous space, where one axis represents
      sensitivity to punishment or threat, and the other, sensitivity to reward.
      Depressed mood and anxious mood represent two different quadrants of this space.
      The adaptive function of mood is to integrate information about the recent state
      of the environment and current physical condition of the organism to fine-tune
      its decisions about the allocation of behavioural effort. Many empirical
      observations from both humans and non-human animals are consistent with this
      model. We discuss the implications of this adaptive approach to mood systems for
      mood disorders in humans.

PMID- 22975003
TI  - Evolution of vertebrate immunity.
AB  - All multicellular organisms protect themselves against pathogens using
      sophisticated immune defenses. Functionally interconnected humoral and cellular
      facilities maintain immune homeostasis in the absence of overt infection and
      regulate the initiation and termination of immune responses directed against
      pathogens. Immune responses of invertebrates, such as flies, are innate and
      usually stereotyped; those of vertebrates, encompassing species as diverse as
      jawless fish and humans, are additionally adaptive, enabling more rapid and
      efficient immune reactivity upon repeated encounters with a pathogen. Many of the
      attributes historically defining innate and adaptive immunity are in fact common
      to both, blurring their functional distinction and emphasizing shared ancestry
      and co-evolution. These findings provide indications of the evolutionary forces
      underlying the origin of somatic diversification of antigen receptors and
      contribute to our understanding of the complex phenotypes of human immune
      disorders. Moreover, informed by phylogenetic considerations and inspired by
      improved knowledge of functional networks, new avenues emerge for innovative
      therapeutic strategies.

PMID- 22975004
TI  - Evolution of inflammatory diseases.
AB  - The association of inflammation with modern human diseases (e.g. obesity,
      cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved
      mystery of current biology and medicine. Inflammation is a protective response to
      noxious stimuli that unavoidably occurs at a cost to normal tissue function. This
      fundamental trade-off between the cost and benefit of the inflammatory response
      has been optimized over evolutionary time for specific environmental conditions.
      Rapid change of the human environment due to niche construction outpaces genetic
      adaptation through natural selection, leading increasingly to a mismatch between
      the modern environment and selected traits. Consequently, multiple trade-offs
      that affect human physiology are not optimized to the modern environment, leading
      to increased disease susceptibility. Here we examine the inflammatory response
      from an evolutionary perspective. We discuss unique aspects of the inflammatory
      response and its evolutionary history that can help explain the association
      between inflammation and modern human diseases.

PMID- 22975005
TI  - Ageing as a risk factor for disease.
AB  - Age is the main risk factor for the prevalent diseases of developed countries:
      cancer, cardiovascular disease and neurodegeneration. The ageing process is
      deleterious for fitness, but can nonetheless evolve as a consequence of the
      declining force of natural selection at later ages, attributable to extrinsic
      hazards to survival: ageing can then occur as a side-effect of accumulation of
      mutations that lower fitness at later ages, or of natural selection in favour of
      mutations that increase fitness of the young but at the cost of a higher
      subsequent rate of ageing. Once thought of as an inexorable, complex and lineage
      specific process of accumulation of damage, ageing has turned out to be
      influenced by mechanisms that show strong evolutionary conservation. Lowered
      activity of the nutrient-sensing insulin/insulin-like growth factor/Target of
      Rapamycin signalling network can extend healthy lifespan in yeast, multicellular
      invertebrates, mice and, possibly, humans. Mitochondrial activity can also
      promote ageing, while genome maintenance and autophagy can protect against it. We
      discuss the relationship between evolutionarily conserved mechanisms of ageing
      and disease, and the associated scientific challenges and opportunities.

PMID- 22975006
TI  - Evolution of neurodegeneration.
AB  - A number of neurodegenerative diseases principally affect humans as they age and
      are characterized by the loss of specific groups of neurons in different brain
      regions. Although these disorders are generally sporadic, it is now clear that
      many of them have a substantial genetic component. As genes are the raw material
      with which evolution works, we might benefit from understanding these genes in an
      evolutionary framework. Here, I will discuss how we can understand whether
      evolution has shaped genes involved in neurodegeneration and the implications for
      practical issues, such as our choice of model systems for studying these
      diseases, and more theoretical concerns, such as the level of selection against
      these phenotypes.

PMID- 22975008
TI  - Cellular hyperproliferation and cancer as evolutionary variables.
AB  - Technological advances in biology have begun to dramatically change the way we
      think about evolution, development, health and disease. The ability to sequence
      the genomes of many individuals within a population, and across multiple species,
      has opened the door to the possibility of answering some long-standing and
      perplexing questions about our own genetic heritage. One such question revolves
      around the nature of cellular hyperproliferation. This cellular behavior is used
      to effect wound healing in most animals, as well as, in some animals, the
      regeneration of lost body parts. Yet at the same time, cellular
      hyperproliferation is the fundamental pathological condition responsible for
      cancers in humans. Here, I will discuss why microevolution, macroevolution and
      developmental biology all have to be taken into consideration when interpreting
      studies of both normal and malignant hyperproliferation. I will also illustrate
      how a synthesis of evolutionary sciences and developmental biology through the
      study of diverse model organisms can inform our understanding of both health and
      disease.

PMID- 22975009
TI  - RNAi-based nanomedicines for targeted personalized therapy.
AB  - RNA interference (RNAi) has just made it through the pipeline to clinical trials.
      However, in order for RNAi to serve as an ideal personalized therapeutics and be
      clinically approved-safe, specific, and potent strategies must be devised for
      efficient delivery of RNAi payloads to specific cell types, which despite the
      immense potential, remains a challenge. Through evaluating the recent reported
      studies in this field, we introduce the progress in designing targeted nano
      scaled strategies that are anticipated to overcome the delivery drawbacks and
      along with the exciting "omics" discipline to personalize RNAi-based
      therapeutics.

PMID- 22975007
TI  - Cancer in light of experimental evolution.
AB  - Cancer initiation, progression, and the emergence of therapeutic resistance are
      evolutionary phenomena of clonal somatic cell populations. Studies in microbial
      experimental evolution and the theoretical work inspired by such studies are
      yielding deep insights into the evolutionary dynamics of clonal populations, yet
      there has been little explicit consideration of the relevance of this rapidly
      growing field to cancer biology. Here, we examine how the understanding of
      mutation, selection, and spatial structure in clonal populations that is emerging
      from experimental evolution may be applicable to cancer. Along the way, we
      discuss some significant ways in which cancer differs from the model systems used
      in experimental evolution. Despite these differences, we argue that enhanced
      prediction and control of cancer may be possible using ideas developed in the
      context of experimental evolution, and we point out some prospects for future
      research at the interface between these traditionally separate areas.

PMID- 22975010
TI  - Surface engineering of inorganic nanoparticles for imaging and therapy.
AB  - Many kinds of inorganic nanoparticles (NPs) including semiconductor, metal, metal
      oxide, and lanthanide-doped NPs have been developed for imaging and therapy
      applications. Their unique optical, magnetic, and electronic properties can be
      tailored by controlling the composition, size, shape, and structure. Interaction
      of such NPs with cells and/or in vivo compartments is critically determined by
      the surface properties, and sophisticated control over the NP surface is
      essential to control their fate in biological environments. We review NP surface
      coating strategies using the categories of small surface ligand, polymer, and
      lipid. Use of small ligand molecules has the advantage of maintaining the minimal
      hydrodynamic (HD) size. Polymers can be advantageous in NP anchoring by combining
      multiple affinity groups. Encapsulation of NPs in polymers, lipids or surfactants
      can preserve the as-synthesized NPs. NP surface properties and reaction
      conditions should be carefully considered to obtain a bioconjugate that maintains
      the physicochemical properties of NP and functionalities of the conjugated
      biomolecules. We highlight how the surface properties of NPs impact their
      interactions with cells and in vivo compartments, especially focused on the
      important surface design parameters such as HD size, surface charge, and
      targeting. Typically, maximal cellular uptake can take place in the intermediate
      NP size range of 40-60nm. Clearance of NPs from blood circulation is largely
      dependent on the degree of uptake by reticuloendothelial system when they are
      larger than 10nm. When the HD size is below 10nm, NPs show broad distribution
      over many organs. Reduction of HD size below the limit of renal barrier can
      achieve fast clearance of NPs. For maximal tumor accumulation, NPs should have
      long blood circulation time and should be large enough to prevent rapid
      penetration. NPs are also desired to rapidly clear out from the body after the
      mission before they cause toxic side effects. However, efficient clearance from
      the body to avoid side effects may result in the reduction in residence time
      required for accumulation in target tissues. Smart design of NP surface coating
      that can meet the conflicting demands can open a new avenue of NP applications.
      Surface charge and hydrophobicity need to be carefully considered for NP surface
      design. Positively charged NPs more adsorb on cell membranes and consequently
      show higher level of internalizations when compared with negatively charged or
      neutral NPs. NPs encounter a large variety of biomolecules in vivo, where non
      specific adsorptions can potentially alter the physicochemical properties of the
      NPs. For optimal performance, NPs are suggested to have neutral surface charge at
      physiological conditions, small HD size, and minimal non-specific adsorption
      levels. Zwitterionic NP surface coating by small surface ligands can be a
      promising approach. Toxicity is one of most critical issues, where proper control
      of the NP surface can significantly reduce the toxicities.

PMID- 22975011
TI  - Molecular and clinical characterization of patients with a ring chromosome 11.
AB  - Ring chromosomes are uncommon cytogenetic findings and are often associated with
      clinical features overlapping the phenotype of patients with terminal deletions
      of the corresponding chromosome. Most of the ring chromosomes arise sporadically
      and parental transmission is rarely observed. We report five patients carrying a
      ring chromosome 11, with three of the patients belonging to the same family. SNP
      array analysis was performed to characterize the different ring chromosomes and
      the clinical phenotypes were compared with previously reported patients with ring
      chromosome 11.

PMID- 22975012
TI  - A de novo 163 kb interstitial 1q44 microdeletion in a boy with thin corpus
      callosum, psychomotor delay and seizures.
AB  - The 1q44 deletion syndrome has shown to be a recognizable phenotype with
      developmental delay, short stature and corpus callosum abnormalities as
      relatively consistent features. However, the disorder is still clinically
      heterogeneous and a genotype-phenotype correlation has been challenging to
      establish. In particular, a delineation of a critical region for the corpus
      callosum development has turned out to be difficult, and many candidate genes
      have been proposed. We present here a patient boy with a clinical picture of the
      1q44 deletion syndrome, including a thin corpus callosum, and a small de novo
      1q44 deletion. The deletion spans a maximum of 163 kb, a region which only
      contains the two genes FAM36A and HNRNPU. This finding supports the previously
      suggested hypothesis that the HNRNPU is an essential gene to the development of
      corpus callosum. However, as patients with deletions outside this interval also
      have been reported to have corpus callosum abnormalities, other mechanisms are
      probably also involved. We also identified two conserved non-coding regions in
      the deleted region of the patient, and speculate that also other elements
      interfere with the complex interplay and spatiotemporal gene expression during
      embryonic development.

PMID- 22975013
TI  - Skeletal age estimation in Hungarian population of known age and sex.
AB  - Several methods of estimating age on the basis of human skeletal remains are used
      all over the world, methods that were established using known age and sex
      databases or during medicolegal autopsies. Over the course of the past several
      decades, many tests have been carried out on various populations to confirm the
      applicability of these methods in age assessment. While the opinions of experts
      vary regarding the cranial suture closure techniques, morphology of the sternal
      end of the fourth rib has been proven to be more accurate as an age assessor. The
      purpose of this paper is to test the reliability of three age estimation methods
      on a Central European population. Observation of ecto- and endocranial suture
      closure after Meindl and Lovejoy and Acsadi and Nemeskeri (239 individuals in the
      case of Meindl and Lovejoy and 238 in the case of Acsadi and Nemeskeri) and
      morphology of the sternal ends of the third, fourth and fifth ribs in accordance
      with Iscan (116 individuals) was done on a Hungarian sample of known sex and age
      at death at autopsy procedures. According to the observations, (1) the state of
      ectocranial suture closure was so erratic that it was not useful in age
      assessment, (2) obliteration phases of the endocranial sutures yield only a rough
      estimation, and (3) age determination from sternal ends of the ribs was the most
      reliable, especially with the application of slightly expanded age intervals on
      the Hungarian population.

PMID- 22975014
TI  - Macrophages in the infarct: fiery friends or friendly fire?

PMID- 22975015
TI  - The protective effect of Ginkgo biloba extract against experimental cisplatin
      ototoxicity: animal research using distortion product otoacoustic emissions.
AB  - BACKGROUND: Cisplatin, an effective therapeutic agent for various human cancers,
      has dose-limiting side effects of ototoxicity and nephrotoxicity. Cisplatin
      ototoxicity is thought to result from increased amounts of toxic free radicals or
      cell membrane changes leading to increased intracellular calcium content. Ginkgo
      biloba extract prevents lipid peroxidation, decreases intracellular free oxygen
      radical levels, regulates the cell membrane calcium transport mechanism and
      prevents cell death. This study aimed to investigate the protective effect of
      Ginkgo biloba extract against cisplatin-induced ototoxicity in rats. METHODS:
      Twenty Wistar albino rats with normal hearing (confirmed by distortion product
      otoacoustic emission testing prior to cisplatin application) were randomly
      allocated to two groups. Both groups received a single intraperitoneal dose of
      cisplatin (12 mg/kg). Group two also received daily intraperitoneal doses of
      Ginkgo biloba extract (100 mg/kg) for 10 days. Distortion product otoacoustic
      emission measurements were repeated on days 10 and 17 and signal-to-noise ratios
      were compared. RESULTS: Compared with group one, group two had significantly
      better distortion product otoacoustic emission results at 3, 4, 6 and 8 kHz on
      days 10 and 17. CONCLUSION: These findings suggest that Ginkgo biloba extract
      protects the inner ear against cisplatin-induced ototoxicity.

PMID- 22975016
TI  - Screening for hyperglycemia in the developing world: rationale, challenges and
      opportunities.
AB  - BACKGROUND: The prevalence of diabetes and prediabetes are increasingly high in
      developing countries, where detection rates remain very low. This manuscript
      discusses the rationale, challenges and opportunities for early detection of
      diabetes and prediabetes in developing countries. METHODS: PubMed was searched up
      to March 2012 for studies addressing screening for hyperglycemia in developing
      countries. Relevant studies were summarized through key questions derived from
      the Wilson and Junger criteria. RESULTS: In developing countries, diabetes
      predominantly affects working-age persons, has high rates of complications and
      devastating economic impacts. These countries are ill-equipped to handle advanced
      stages of the disease. There are acceptable and relatively simple tools that can
      aid screening in these countries. Interventions shown to be cost-effective in
      preventing diabetes and its complications in developed countries can be used in
      screen-detected people of developing countries. However, effective implementation
      of these interventions remains a challenge, and the costs and benefits of
      diabetes screening in these settings are less well-known. Implementing screening
      policies in developing countries will require health systems strengthening,
      through creative funding and staff training. CONCLUSIONS: For many compelling
      reasons, screening for hyperglycemia preferably targeted, should be a policy
      priority in developing countries. This will help reorient health systems toward
      cost-saving prevention.

PMID- 22975017
TI  - Managing variations from surgical care plans: challenges for coordination.
AB  - INTRODUCTION: In surgical work there is a need for 'continuous planning' among
      staff to handle the frequently occurring variations from the planned patient
      treatment. In this paper, we present how three hospital information systems have
      support for three common patient trajectory variations. PURPOSE: Highlight how
      deviations from a plan cause different information needs and implications for
      design of awareness supporting computer systems. METHODS: Participant
      observations and semi-structured interviews with stakeholders involved in peri
      operative work. RESULTS: When trajectories progress according to plan,
      information needs of staff seem to be minimal, as everything is "running to
      plan". However, when variations occur the information need increases. In order to
      provide better support for variations, awareness-support systems need to inform
      colleagues and other stakeholders about deviations from the plan. Plans and
      trajectories also need to be connected by projecting estimations of incidental
      time of ongoing relevant events. Additionally, end-users should have the option
      to switch between information-sparse and information-rich computer support.

PMID- 22975018
TI  - Telemedicine across borders: a systematic review of factors that hinder or
      support implementation.
AB  - PURPOSE: Innovative technologies to deliver health care across borders have
      attracted both evangelists and sceptics. Our aim was to systematically identify
      factors that hinder or support implementation of cross-border telemedicine
      services worldwide in the last two decades. METHODS: Two reviewers independently
      searched ten databases including MEDLINE and EMBASE, in June 2011 including
      citations from 1990 onwards when at least an abstract was available in English.
      We also searched ELDIS and INTUTE databases and Internet search engines to
      identify grey literature. We included studies which (a) described the use of
      telemedicine to deliver cross-border healthcare and, or (b) described the factors
      that hinder or support implementation of cross-border telemedicine services. All
      study designs were included. Two reviewers independently assessed titles and
      abstracts of articles identified. Papers were allocated to one of four reviewers
      who extracted relevant data and validated it. We took a qualitative approach to
      the analysis, conducting a narrative synthesis of the evidence. RESULTS: 6026
      records were identified of which 5806 were excluded following screening of titles
      and abstracts. We assessed 227 full text articles, excluding 133 because they
      were fatally flawed or did not meet the inclusion criteria, producing a final
      sample of 94. They involved 76 countries worldwide, most involving collaborations
      between high and low or middle income countries. Most described services
      delivering a combination of types of telemedicine but specialties most
      represented were telepathology, telesurgery, Emergency and trauma telemedicine
      and teleradiology. Most link health professionals, with only a few linking
      professionals directly to patients. A main driver for the development of cross
      border telemedicine is the need to improve access to specialist services in low
      and middle income countries and in underserved rural areas in high income
      countries. Factors that hinder or support implementation clustered into four main
      themes: (1) legal factors; (2) sustainability factors; (3) cultural factors; and
      (4) contextual factors. CONCLUSIONS: National telemedicine programmes may build
      infrastructure and change mindsets, laying the foundations for successful
      engagement in cross-border services. Regional networks can also help with sharing
      of expertise and innovative ways of overcoming barriers to the implementation of
      services. Strong team leadership, training, flexible and locally responsive
      services delivered at low cost, using simple technologies, and within a clear
      legal and regulatory framework, are all important factors for the successful
      implementation of cross-border telemedicine services.

PMID- 22975019
TI  - Intrinsic proinflammatory signaling in podocytes contributes to podocyte damage
      and prolonged proteinuria.
AB  - Inflammation conveys the development of glomerular injury and is a major cause of
      progressive kidney disease. NF-kappaB signaling is among the most important
      regulators of proinflammatory signaling. Its role in podocytes, the epithelial
      cells at the kidney filtration barrier, is poorly understood. Here, we inhibited
      NF-kappaB signaling in podocytes by specific ablation of the NF-kappaB essential
      modulator (NEMO, IKKgamma). Podocyte-specific NEMO-deficient mice (NEMO(pko))
      were viable and did not show proteinuria or overt changes in kidney morphology.
      After induction of glomerulonephritis, both NEMO(pko) and control mice developed
      significant proteinuria. However, NEMO(pko) mice recovered much faster, showing
      rapid remission of proteinuria and restoration of podocyte morphology.
      Interestingly, quantification of infiltrating macrophages, T-lymphocytes, and
      granulocytes at day 7 revealed no significant difference between wild-type and
      NEMO(pko). To further investigate the underlying mechanisms, we created a stable
      NEMO knockdown mouse podocyte cell line. Again, no overt changes in morphology
      were observed. Translocation of NF-kappaB to the nucleus after stimulation with
      TNFalpha or IL-1 was sufficiently inhibited. Moreover, secretion of
      proinflammatory chemokines from podocytes after stimulation with TNFalpha or IL-1
      was significantly reduced in NEMO-deficient podocytes and in glomerular samples
      obtained at day 7 after induction of nephrotoxic nephritis. Collectively, these
      results show that proinflammatory activity of NF-kappaB in podocytes aggravates
      proteinuria in experimental glomerulonephritis in mice. Based on these data, it
      may be speculated that immunosuppressive drugs may not only target professional
      immune cells but also podocytes directly to convey their beneficial effects in
      various types of glomerulonephritis.

PMID- 22975020
TI  - Multinephron dynamics on the renal vascular network.
AB  - Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each
      nephron to regulate blood flow and glomerular filtration rate. Both mechanisms
      are nonlinear, generate self-sustained oscillations, and interact as their
      signals converge on arteriolar smooth muscle, forming a regulatory ensemble.
      Ensembles may synchronize. Smooth muscle cells in the ensemble depolarize
      periodically, generating electrical signals that propagate along the vascular
      network. We developed a mathematical model of a nephron-vascular network, with 16
      versions of a single nephron model containing representations of both mechanisms
      in the regulatory ensemble, to examine the effects of network structure on
      nephron synchronization. Symmetry, as a property of a network, facilitates
      synchronization. Nephrons received blood from a symmetric electrically conductive
      vascular tree. Symmetry was created by using identical nephron models at each of
      the 16 sites and symmetry breaking by varying nephron length. The symmetric model
      achieved synchronization of all elements in the network. As little as 1%
      variation in nephron length caused extensive desynchronization, although
      synchronization was maintained in small nephron clusters. In-phase
      synchronization predominated among nephrons separated by one or three vascular
      nodes and antiphase synchronization for five or seven nodes of separation.
      Nephron dynamics were irregular and contained low-frequency fluctuations. Results
      are consistent with simultaneous blood flow measurements in multiple nephrons. An
      interaction between electrical signals propagated through the network to cause
      synchronization; variation in vascular pressure at vessel bifurcations was a
      principal cause of desynchronization. The results suggest that the vasculature
      supplies blood to nephrons but also engages in robust information transfer.

PMID- 22975021
TI  - Disruption of skeletal muscle mitochondrial network genes and miRNAs in
      amyotrophic lateral sclerosis.
AB  - Skeletal muscle mitochondrial dysfunction is believed to play a role in the
      progression and severity of amyotrophic lateral sclerosis (ALS). The regulation
      of transcriptional co-activators involved in mitochondrial biogenesis and
      function in ALS is not well known. When compared with healthy control subjects,
      patients with ALS, but not neurogenic disease (ND), had lower levels of skeletal
      muscle peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha) mRNA and protein and estrogen-related receptor-alpha (ERRalpha) and
      mitofusin-2 (Mfn2) mRNA. PGC-1beta, nuclear respiratory factor-1 (NRF-1) and Mfn1
      mRNA as well as cytochrome C oxidase subunit IV (COXIV) mRNA and protein were
      lower in patients with ALS and ND. Both patient groups had reductions in citrate
      synthase and cytochrome c oxidase activity. Similar observations were made in
      skeletal muscle from transgenic ALS G93A transgenic mice. In vitro, PGC-1alpha
      and PGC-1beta regulated Mfn1 and Mfn2 in an ERRalpha-dependent manner. Compared
      to healthy controls, miRNA 23a, 29b, 206 and 455 were increased in skeletal
      muscle of ALS patients. miR-23a repressed PGC-1alpha translation in a 3' UTR
      dependent manner. Transgenic mice over expressing miR-23a had a reduction in PGC
      1alpha, cytochome-b and COXIV protein levels. These results show that skeletal
      muscle mitochondrial dysfunction in ALS patients is associated with a reduction
      in PGC-1alpha signalling networks involved in mitochondrial biogenesis and
      function, as well as increases in several miRNAs potentially implicated in
      skeletal muscle and neuromuscular junction regeneration. As miR-23a negatively
      regulates PGC-1alpha signalling, therapeutic inhibition of miR-23a may be a
      strategy to rescue PGC-1alpha activity and ameliorate skeletal muscle
      mitochondrial function in ALS. 

PMID- 22975022
TI  - Prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest.
AB  - OBJECTIVE: We sought to investigate the prognostic implication of early
      coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest
      (OHCA). METHODS: OHCA registry was analyzed to identify patients with ROSC
      without recent use of anticoagulant between 2008 and 2011. Patients were assessed
      for prehosptial factors, initial laboratory results and therapeutic hypothermia.
      Outcome variables were survival discharge, 6-month CPC and survival duration
      within the first week after ROSC. Logistic regression and Cox proportional
      hazards models were used for both univariable and multivariable analysis.
      RESULTS: Among 273 eligible patients, initial DIC score was available in 252
      (92.3%). Higher DIC score was associated with increased inhospital death (odds
      ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48-2.41) and
      unfavorable long-term outcome (6-month CPC 3-5; OR, 2.21 per unit; 95% CI, 1.60
      3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17-2.22) and 1.84
      (95% CI, 1.26-2.67), respectively. We categorized DIC score in five groups as <3,
      3, 4, 5 and >5 and analyzed differential mortality risk using Cox proportional
      hazards model. Compared with reference group (DIC score<3), the adjusted HR for
      early mortality in each remaining group was 1.96 (95% CI, 1.13-3.40), 2.26 (95%
      CI, 1.27-4.02), 2.77 (95% CI, 1.58-4.85) and 4.29 (95% CI, 2.22-8.30),
      respectively (p-trend<0.001). The area under the receiver operating
      characteristic of DIC score for prediction of unfavorable long-term outcome was
      0.79 (95% CI, 0.69-0.88). CONCLUSION: Increased initial DIC score in OHCA was an
      independent predictor for poor outcomes and early mortality risk.

PMID- 22975023
TI  - Clinical validation of an Internet-based questionnaire for ascertaining hip and
      knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the measurement properties of an Internet-based self
      administered questionnaire in ascertaining cases of hip and knee osteoarthritis
      (OA). METHODS: Questionnaire data from 4269 Canadian subjects aged 45-85 were
      collected on hip and knee joint health including self-reported items on medically
      diagnosed hip and knee OA and joint replacement. A sub-cohort of 100 subjects was
      recruited for clinical examination. The self-reported outcomes were evaluated
      using the American College of Rheumatology clinical classification criteria for
      hip and knee OA as the gold standard for clinical verification. Analysis was at
      the joint level (200 knees, 200 hips). Validity was examined using sensitivity,
      specificity, and predictive values; to account for correlated joints of the same
      subject, bootstrapping was performed to yield valid 95% confidence interval
      (CI's). RESULTS: Self-reported measures for a medical diagnosis of knee OA had a
      positive predictive value of 86%, negative predictive value 91%, sensitivity 73%
      and specificity 96% for correctly identifying clinical knee OA. For hip OA, the
      values were 61%, 98%, 81% and 94% respectively. CONCLUSION: Internet self-report
      of medically-diagnosed hip and knee OA in metro Vancouver residents correctly
      identified most cases and non-cases of clinical OA when compared with the ACR
      clinical classification criteria gold standard. In particular, specificity was
      very high, important in risk factor studies due to the profound effect of even
      small losses in specificity on the measure of association. The findings provide
      evidence that these questionnaire case definitions have utility for identifying
      hip and knee OA in community and population-based studies when the purpose is to
      link potential risk factors with knee and hip health.

PMID- 22975024
TI  - Investigation of potentially toxic heavy metals in different organic wastes used
      to fertilize market garden crops.
AB  - The benefits of using organic waste as fertilizer and soil amendment should be
      assessed together with the environmental impacts due to the possible presence of
      heavy metals (HMs). This study involved analysing major element and HM contents
      in raw and size-fractionated organic wastes (17 sewage sludges and composts) from
      developed and developing countries. The overall HM concentration pattern showed
      an asymmetric distribution due to the presence of some wastes with extremely high
      concentrations. HM concentrations were correlated with the size of cities or
      farms where the wastes had been produced, and HM were differentiated with respect
      to their origins (geogenic: Cr-Ni; anthropogenic agricultural and urban: Cu-Zn;
      anthropogenic urban: Cd-Pb). Size fractionation highlighted Cd, Cu, Zn and Pb
      accumulation in fine size fractions, while Cr and Ni were accumulated in the
      coarsest. HM associations with major elements revealed inorganic (Al, Fe, etc.)
      bearing phases for Cr and Ni, and sulfur or phosphorus species for Cd, Cu Pb and
      Zn.

PMID- 22975025
TI  - Effects of immunization with natural and recombinant lysine decarboxylase on
      canine gingivitis development.
AB  - Periodontal disease, gingival inflammation (gingivitis) and periodontal
      attachment loss (periodontitis), causes tooth loss and susceptibility to chronic
      inflammation. Professionally scaling and cleaning the teeth regularly controls
      the disease, but is expensive in companion animals. Eikenella corrodens is common
      in canine oral cavities where it is a source of lysine decarboxylase (LDC). In
      human dental biofilms (plaques), LDC converts lysine to cadaverine and impairs
      the gingival epithelial barrier to bacteria. LDC vaccination may therefore retard
      gingivitis development. Year-old beagle dogs provided blood samples, and had
      weight and clinical measurements (biofilm and gingivitis) recorded. After scaling
      and cleaning, two dogs were immunized subcutaneously with 0.2mg native LDC from
      E. corrodens and 2 sets of four dogs with 0.2mg recombinant LDC purified from
      Escherichia coli. A third set of 4 dogs was immunized intranasally.
      Rehydragel((r)), Emulsigen((r)), PolygenTM or CarbigenTM were used as adjuvant.
      Four additional pairs of dogs were sham-immunized with each adjuvant alone
      (controls). Immunizations were repeated twice, 3 weeks apart, and clinical
      measurements were obtained after another 2 weeks, when the teeth were scaled and
      cleaned again. Tooth brushing was then stopped and the diet was changed from hard
      to soft chow. Clinical measurements were repeated after 1, 2, 3, 4, 6 and 8
      weeks. Compared with sham-immunized dogs, gingivitis was reduced over all 8 weeks
      of soft diet after subcutaneous immunization with native LDC, or after intranasal
      immunization with recombinant LDC in CarbigenTM, but for only 6 of the 8 weeks
      after subcutaneous immunization with recombinant LDC in Emulsigen((r)) (repeated
      measures ANOVA). Subcutaneous vaccination induced a strong serum IgG antibody
      response that decreased during the soft diet period, whereas intranasal
      immunization induced a weak serum IgA antibody response that did not decrease.
      Immunization with recombinant LDC may provide protection from gingivitis if
      procedures are optimized.

PMID- 22975026
TI  - Febrile seizures and measles-mumps-rubella-varicella (MMRV) vaccine: what do
      primary care physicians think?
AB  - PURPOSE: Measles-mumps-rubella-varicella (MMRV) vaccine is associated with
      increased febrile seizure risk compared with measles-mumps-rubella and varicella
      vaccine given separately (MMR+V) in children 12-15-month old. We assessed
      knowledge regarding MMRV and febrile seizures, intended practices, and factors
      influencing the decision to recommend MMRV. METHODS: National survey administered
      10/2008-1/2009 of US pediatricians (Peds) and family physicians (FP). RESULTS:
      Response rate was 73% (620/849). Twenty-nine percent of Peds and 74% of FP
      (p<0.001) were unaware of increased febrile seizure risk after MMRV. After
      reading an informational statement, 20% of Peds and 7% of FP (p<0.001) would
      recommend MMRV to a healthy 12-15-month-old child. The factor most frequently
      reported as "very important" in the decision to recommend MMRV or MMR+V was
      ACIP/AAFP/AAP recommendations (pediatricians, 77%, family physicians, 73%,
      p=0.08). CONCLUSIONS: After receiving data regarding febrile seizure risk after
      MMRV, few physicians report they would recommend MMRV to a healthy 12-15-month
      old child.

PMID- 22975027
TI  - Resveratrol initiates differentiation of mouse skeletal muscle-derived C2C12
      myoblasts.
AB  - Resveratrol is one of the most widely studied bio-active plant polyphenols. While
      its effect on endothelial blood vessel cells, cancer cells, inflammatory
      processes and neurodegenerative events is well documented, little is known about
      the implication of this phytophenol in differentiating processes, particularly in
      skeletal muscle cells. Here, we report the effects of resveratrol on mouse
      skeletal muscle-derived cells (C2C12) in either a nondifferentiated (myoblasts)
      or differentiated state (myotubes) by evaluating resveratrol uptake, cell
      proliferation, changes in cell shape, and the expression of genes encoding muscle
      specific transcription factors or contractile proteins. Resveratrol: (1) rapidly
      accumulates within cells through passive and facilitated processes; (2) does not
      strongly affect cell viability, cell cycle and apoptosis; (3) behaves as a pro
      differentiating agent as shown by the lengthening of cells, leading to a myotube
      phenotype; (4) upregulates muscular pro-differentiation markers and transcription
      factors (myogenin, Scrp3) starting after 12h of exposure and strongly increases
      heavy chain myosin content after 18h of exposure to resveratrol; (5) increases
      the Srf transcription factor's transcript level, a target mRNA of the miRNA-133b,
      which is itself downregulated by this polyphenol. These results put forward new
      pro-differentiating regulatory properties of resveratrol on skeletal muscles at
      least partly via modulation of specific miRNAs.

PMID- 22975028
TI  - Aryl-hydrocarbon receptor activity modulates prolactin expression in the
      pituitary.
AB  - Pituitary tumors account for 15% of intracranial neoplasms, however the extent to
      which environmental toxicants contribute to the proliferation and hormone
      expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR)
      interacting protein (AIP) loss of function mutations cause somatotrope and
      lactotrope adenomas in humans. AIP sequesters AhR and inhibits its
      transcriptional function. Because of the link between AIP and pituitary tumors,
      we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that
      are persistent in the environment, may predispose to pituitary dysfunction
      through activation of AhR. In the present study, we examined the effect of AhR
      activation on proliferation and endogenous pituitary hormone expression in the
      GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in
      knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist beta
      naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the
      anti-proliferative signaling cytokine TGFbeta1 are suppressed upon beta
      naphthoflavone treatment, we did not observe an alteration in cell proliferation.
      AhR activation with beta-naphthoflavone suppresses Ahr expression and impairs
      expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In
      mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is
      unaffected. Additionally, there is a significant reduction in pituitary hormones
      Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR
      is important for pituitary hormone expression and suggest that environmental
      dioxins can exert endocrine disrupting effects at the pituitary.

PMID- 22975030
TI  - New targets for rTMS in depression: a review of convergent evidence.
AB  - Although rTMS is moving steadily into the mainstream as a treatment for medically
      refractory depression, its efficacy continues to lag behind that of more invasive
      neuromodulation treatments such as ECT or DBS. Here we review evidence to suggest
      that a fruitful, but neglected, strategy for improving rTMS efficacy may be to
      explore alternatives to the conventional stimulation target in the dorsolateral
      prefrontal cortex (DLPFC). The convergent evidence of lesion, stimulation,
      connectivity, and correlative neuroimaging studies suggests that the DLPFC may
      have a relatively peripheral role in mood regulation, at least compared to
      several alternative areas within the prefrontal cortex. In particular, we
      consider the evidence base in support of four new potential targets for rTMS in
      depression: dorsomedial prefrontal cortex (DMPFC), frontopolar cortex (FPC),
      ventromedial prefrontal cortex (VMPFC), and ventrolateral prefrontal cortex
      (VLPFC). Each of these regions enjoys broader support, from a more diverse
      evidence base, than the DLPFC in terms of its role in emotion regulation in major
      depression. We discuss the relative merits of each of these novel targets,
      including potential obstacles to stimulation using currently available
      technologies, and potential strategies for overcoming these obstacles. It is
      hoped that this detailed review will spur a more vigorous exploration of new
      targets for rTMS in depression. The use of new targets may help to propel rTMS
      across the threshold of efficacy required of a first-line treatment, to assume a
      more widespread role in the treatment of depressed mood.

PMID- 22975029
TI  - Sulforaphane prevents pulmonary damage in response to inhaled arsenic by
      activating the Nrf2-defense response.
AB  - Exposure to arsenic is associated with an increased risk of lung disease. Novel
      strategies are needed to reduce the adverse health effects associated with
      arsenic exposure in the lung. Nrf2, a transcription factor that mediates an
      adaptive cellular defense response, is effective in detoxifying environmental
      insults and prevents a broad spectrum of diseases induced by environmental
      exposure to harmful substances. In this report, we tested whether Nrf2 activation
      protects mice from arsenic-induced toxicity. We used an in vivo arsenic
      inhalation model that is highly relevant to low environmental human exposure to
      arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted
      in pathological alterations, oxidative DNA damage, and mild apoptotic cell death
      in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent
      manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory
      responses by modulating cytokine production. This study provides strong evidence
      that dietary intervention targeting Nrf2 activation is a feasible approach to
      reduce adverse health effects associated with arsenic exposure.

PMID- 22975031
TI  - Ultrasound investigation during labour of consensual or nonconsensual fetal spine
      in an occiput posterior cephalic presentation can improve the management of
      delivery?

PMID- 22975033
TI  - The volume of the neovascularity and its clinical implications in achilles
      tendinopathy.
AB  - Thirty-seven pathologic Achilles tendons from 27 patients were investigated by a
      three-dimensional (3-D) power Doppler ultrasound system. Both the volume of the
      neovascularity (VON) and the volume of Achilles tendon (VOAT) were investigated.
      VON-VOAT index (VVI), as the normalization of the neovascularization, was
      accordingly calculated. Patient's clinical indications were assessed using the
      visual analog scale for pain (VAS) and Victorian Institute of Sport Assessment
      Achilles (VISA-A). Relationships between VAS and VON, VISA-A and VON, VAS and
      VOAT, VISA-A and VOAT, VAS and VVI, and VISA-A and VVI, were statistically
      analyzed. The vascular mapping within and surrounding the symptomatic Achilles
      tendons was investigated. 97.3% of the Achilles tendons were found to have
      neovascularization. In 55.6% of these Achilles, the neovascularity was associated
      with the location of thickening. The VAS was found to be positively correlated
      with the VON and the VVI, the VON was found to be independent from the VOAT.

PMID- 22975032
TI  - Noninvasive estimation of the blood pressure waveform in the carotid artery using
      continuous finger blood pressure monitoring.
AB  - To noninvasively estimate the blood pressure continuously in the common carotid
      artery (CCA), we obtained the distension waveform of the CCA from seven healthy
      volunteers and 20 hypertensive patients using radio-frequency ultrasound.
      Consequently, it was calibrated by the mean and diastolic pressure measured in
      the finger artery and compared with applanation tonometry, calibrated using the
      systolic and diastolic pressure in the brachial artery. The mean difference in
      estimating the mean blood pressure was 0.3 mm Hg (limits of agreement: -11.7 to
      12.3 mm Hg). In estimating the systolic blood pressure, the mean difference was
      8.0 mm Hg (limits of agreement: -29.8 to 45.8 mm Hg) and showed increasing
      variation with blood pressure. The systolic blood pressure values can be expected
      between 0.83 and 1.35 times the control method. In this study, we obtained proof
      of-principle for noninvasively measuring blood pressure in the CCA using
      continuous finger blood pressure monitoring. This opens the way to estimating
      location specific arterial stiffness and intra-plaque elasticity.

PMID- 22975034
TI  - Acoustic radiation force for vascular cell therapy: in vitro validation.
AB  - Cell-based therapeutic approaches are attractive for the restoration of the
      protective endothelial layer in arteries affected by atherosclerosis or following
      angioplasty and stenting. We have recently demonstrated a novel technique for the
      delivery of mesenchymal stem cells (MSCs) that are surface-coated with cationic
      lipid microbubbles (MBs) and displaced by acoustic radiation force (ARF) to a
      site of arterial injury. The objective of this study was to characterize
      ultrasound parameters for effective acoustic-based delivery of cell therapy. In
      vitro experiments were performed in a vascular flow phantom where MB-tagged MSCs
      were delivered toward the phantom wall using ARF generated with an intravascular
      ultrasound catheter. The translation motion velocity and adhesion of the MB-cell
      complexes were analyzed. Experimental data indicated that MSC radial velocity and
      adhesion to the vessel phantom increased with the time-averaged ultrasound
      intensity up to 1.65 W/cm2, after which no further significant adhesion was
      observed. Temperature increase from baseline near the catheter was 5.5 +/- 0.8
      degrees C with this setting. Using higher time-averaged ultrasound intensities
      may not significantly benefit the adhesion of MB-cell complexes to the target
      vessel wall (p = NS), but could cause undesirable biologic effects such as
      heating to the MB-cell complexes and surrounding tissue. For the highest time
      averaged ultrasound intensity of 6.60 W/cm2, the temperature increase was 11.6 +/
      1.3 degrees C.

PMID- 22975035
TI  - Frequency specific ultrasound attenuation is sensitive to trabecular bone
      structure.
AB  - This study investigated the efficacy of frequency modulated ultrasound
      attenuation in the assessment of the trabecular structural properties. Four
      frequency modulated signals were created to represent four frequency bands
      centered at 500 kHz, 900 kHz, 1.3 MHz and 1.7 MHz with the bandwidth of 400 kHz.
      Five 1-cm trabecular cubes were harvested from fresh bovine distal femur. The
      cubes underwent four steps of demineralization process to expand the sample size
      to 25 with the greater variations of the structural properties for the better
      correlation study. Pearson correlation study was performed between the ultrasound
      attenuation in four frequency bands and the trabecular structural properties. The
      results showed that correlations of frequency modulated ultrasound attenuation to
      the trabecular structural properties are dependent on frequency bands. The
      attenuation in proximal-distal orientation had the highest correlation to BV/TV
      (R(2) = 0.73, p < 0.001) and trabecular thickness (R(2) = 0.50, p < 0.001) at the
      frequency band centered at 1.7 MHz. It was equivalent in the four frequency bands
      in correlation to the trabecular number (average R(2) = 0.80, p < 0.001) and to
      the trabecular separation (average R(2) = 0.83, p < 0.001). The attenuation in
      anterio-posterial orientation had the highest correlation to BV/TV (R(2) = 0.80,
      p < 0.001) and trabecular thickness (R(2) = 0.71, p < 0.001) at the frequency
      band centered at 1.3 MHz. The attenuation in the first frequency band was the
      most sensitive to the trabecular number (R(2) = 0.71, p < 0.001) and trabecular
      separation (R(2) = 0.80, p < 0.001). No significant correlation was observed for
      the attenuation in medial-lateral orientation across the four frequency bands.

PMID- 22975036
TI  - On the advantages of imaging the axial-shear strain component of the total shear
      strain in breast tumors.
AB  - Axial-shear strain elastography was described recently as a method to visualize
      the state of bonding at an inclusion boundary. Although total shear strain
      elastography was initially proposed for this purpose, it did not evolve beyond
      the initial reported finite element model (FEM) and simulation studies. One of
      the major reasons for this was the practical limitation in estimating the tissue
      motion perpendicular (lateral) to the ultrasound (US) beam as accurately as the
      motion along the US beam (axial). Nevertheless, there has been a sustained effort
      in developing methods to improve the lateral motion tracking accuracy and thereby
      obtain better quality total shear strain elastogram (TSSE). We hypothesize that
      in some cases, even if good quality TSSE becomes possible, it may still be
      advantageous to utilize only the axial-shear strain (one of the components of the
      total shear strain) elastogram (ASSE). Specifically, we show through FEM and
      corroborating tissue-mimicking gelatin phantom experiments that the unique "fill
      in" discriminant feature that was introduced recently for asymmetric breast
      lesion classification is depicted only in the ASSE and not in the TSSE. Note that
      the presence or conspicuous absence of this feature in ASSE was shown to
      characterize asymmetric inclusions' boundaries as either loosely-bonded or firmly
      bonded to the surrounding, respectively. This might be an important observation
      because the literature suggests that benign breast lesions tend to be loosely
      bonded, while malignant tumors are usually firmly-bonded. The results from the
      current study demonstrate that the use of shear strain lesion "fill-in" as a
      discriminant feature in the differentiation between asymmetric malignant and
      benign breast lesions is only possible when using the ASSEs and not the TSSEs.

PMID- 22975037
TI  - False negative results of preoperative axillary ultrasound in patients with
      invasive breast cancer: correlations with clinicopathologic findings.
AB  - The purpose of this study was to investigate false-negative results of
      preoperative axillary ultrasound (US) and to evaluate clinicopathologic factors
      related to false-negative results in patients with invasive breast cancer. Four
      hundred eighty-two patients with 483 invasive breast cancers who had no
      suspicious findings on preoperative axillary US were included in this study. All
      patients underwent sentinel lymph node biopsy (SLNB) or axillary lymph node
      dissection. False-negative and true-negative results were compared in terms of
      age, body mass index (BMI), T-stage, pathologic N-stage and final diagnosis of
      breast cancer. Statistical analyses were performed using the chi-square or
      Fisher's exact tests. Of the 483 axillae with negative results on axillary US, 93
      axillae of 93 patients showed false-negative results and the negative predictive
      value of axillary US was 80.8% (390/483). Seventy-five axillae (15.5%, 75/483)
      had N1 and 18 axillae (3.7%, 18/483) had N2 or N3 disease. Eighteen false
      negative results with N2/N3 disease showed a significantly higher T stage (T2/T3)
      than those with N1 disease. As the T-stage increased, false-negative results were
      found more often on preoperative axillary US (p < 0.05). Age, BMI and final
      diagnosis of primary breast cancer were not associated with false-negative
      results on preoperative axillary US. Preoperative axillary US alone is
      insufficiently specific to obviate the need for SLNB because of the substantial
      number of false-negative results in patients with invasive breast cancer,
      although preoperative axillary US alone may exclude most cases of N2 and N3
      disease.

PMID- 22975038
TI  - Whole breast lesion detection using naive bayes classifier for portable
      ultrasound.
AB  - In recent years, portable PC-based ultrasound (US) imaging systems developed by
      some companies can provide an integrated computer environment for computer-aided
      diagnosis and detection applications. In this article, an automatic whole breast
      lesion detection system based on the naive Bayes classifier using the PC-based US
      system Terason t3000 (Terason Ultrasound, Burlington, MA, USA) with a hand-held
      probe is proposed. To easily retrieve the US images for any regions of the
      breast, a clock-based storing system is proposed to record the scanned US images.
      A computer-aided detection (CAD) system is also developed to save the physicians'
      time for a huge volume of scanned US images. The pixel classification of the US
      is based on the naive Bayes classifier for the proposed lesion detection system.
      The pixels of the US are classified into two types: lesions or normal tissues.
      The connected component labeling is applied to find the suspected lesions in the
      image. Consequently, the labeled two-dimensional suspected regions are separated
      into two clusters and further checked by two-phase lesion selection criteria for
      the determination of the real lesion, while reducing the false-positive rate. The
      free-response operative characteristics (FROC) curve is used to evaluate the
      detection performance of the proposed system. According to the experimental
      results of 31 cases with 33 lesions, the proposed system yields a 93.4% (31/33)
      sensitivity at 4.22 false positives (FPs) per hundred slices. Moreover, the speed
      for the proposed detection scheme achieves 12.3 frames per second (fps) with an
      Intel Dual-Core Quad 3 GHz processor and can be also effectively and efficiently
      used for other screening systems.

PMID- 22975039
TI  - Experimental studies and clinical experiences on treatment of secondary
      hypersplenism with extracorporeal high-intensity focused ultrasound.
AB  - The aim of this study is to investigate the efficacy and safety of extracorporeal
      high-intensity focused ultrasound (HIFU) in treatment of hypersplenism. Fifteen
      adult dogs, weighing 13-18 kg were divided into three groups: sham group, SVL
      group undergoing splenic vein ligation (SVL) after laparotomy, and SVL + HIFU
      group receiving SVL followed by extracorporeal HIFU. Pathologic and hematologic
      analyses were performed. We also reviewed the clinical data of 19 patients with
      secondary hypersplenism caused by liver cirrhosis or hepatocellular carcinoma who
      underwent extracorporeal HIFU. Extracorporeal HIFU significantly diminished the
      volume of the spleen of animals, coupled with occurrence of coagulation necrosis
      and fibrosis in the target area. Both platelet and red blood cell counts were
      significantly restored by HIFU intervention. Similarly, HIFU treatment improved
      the hematologic parameters in patients with hypersplenism, and no major
      complications were encountered. Extracorporeal HIFU intervention is effective and
      safe in managing secondary hypersplenism.

PMID- 22975040
TI  - Listening to the cochlea with high-frequency ultrasound.
AB  - We have developed a high-frequency pulsed-wave Doppler ultrasound probe as a
      promising minimally-invasive technique for measuring intracochlear mechanics
      without damaging the cochlea. Using a custom high-frequency ultrasound system, we
      have measured dynamic motion of intracochlear structures by recording the pulsed
      wave Doppler signal resulting from the vibration of the basilar and round window
      membranes. A 45 MHz needle-mounted Doppler probe was fabricated and placed
      against the round window membranes of eight different fresh human temporal bones.
      Pulsed-wave ultrasonic Doppler measurements were performed on the basilar
      membrane and round window membrane during the application of pure tones to the
      external ear canal. Doppler vibrational information for acoustic input
      frequencies ranging from 100-2000 Hz was collected and normalized to the sound
      pressure in the ear canal. The middle ear resonance, located at approximately
      1000 Hz, could be characterized from the membrane velocities, which agreed well
      with literature values. The maximum normalized mean velocity of the round window
      and the basilar membrane were 180 MUm/s/Pa and 27 MUm/s/Pa at 800 Hz. The mean
      phase difference between the membrane displacements and the applied ear canal
      sound pressure showed a flat response almost up to 500 Hz where it began to
      accumulate. This is the first study that reports the application of high
      frequency pulsed wave Doppler ultrasound for measuring the vibration of basilar
      membrane through the round window. Since it is not required to open or damage the
      cochlea, this technique might be applicable for investigating cochlear dynamics,
      in vivo.

PMID- 22975041
TI  - Vascular morphology and tortuosity analysis of breast tumor inside and outside
      contour by 3-D power Doppler ultrasound.
AB  - This study aimed to evaluate morphologic and tortuous features of vessels inside
      and outside the tumor region on three-dimensional power Doppler ultrasonography
      (PDUS) in 113 breast mass lesions, including 60 benign and 53 malignant tumors.
      Compared with benign lesions, malignant breast lesions had significantly larger
      values of vascular morphologic and tortuous features and larger tumor sizes. The
      receiver operating characteristic curve analysis and Student's t-test were used
      to estimate the performance of a proposed classification system using 13 vascular
      features and tumor size selected by the neural network. Accuracy, sensitivity,
      specificity, positive predictive value, negative predictive value and the A(Z)
      value of the diagnosis performance based on 14 features were 89.38% (101/113),
      84.91% (45/53), 93.33% (56/60), 91.84% (45/49), 87.50% (56/64) and 0.9188,
      respectively. The three-dimensional PDUS morphologic and tortuous characteristics
      of blood vessels inside and outside breast mass lesions can be effectively used
      to classify benign and malignant tumors.

PMID- 22975042
TI  - Transcriptional elongation and alternative splicing.
AB  - Alternative splicing has emerged as a key contributor to proteome diversity,
      highlighting the importance of understanding its regulation. In recent years it
      became apparent that splicing is predominantly cotranscriptional, allowing for
      crosstalk between these two nuclear processes. We discuss some of the links
      between transcription and splicing, with special emphasis on the role played by
      transcription elongation in the regulation of alternative splicing events and in
      particular the kinetic model of alternative splicing regulation. This article is
      part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22975043
TI  - History to the discovery of ghrelin.
AB  - The most important initial historical time points in the development of the
      enlarging ghrelin system were 1973, 1976, 1982, 1984, 1990, 1996, 1998, and 1999.
      At these respective times, the following occurred sequentially: isolation of
      somatostatin, discovery of unnatural growth-hormone-releasing peptides (GHRPs),
      isolation of growth-hormone-releasing hormone (GHRH), hypothesis of a new natural
      GHRP different from GHRH, GHRP+GHRH synergism in humans, discovery of the growth
      hormone secretagogue GHS/GHRP receptor, cloning of the receptor, and finally,
      isolation and identification of the new natural endogenous GHRP ghrelin. To
      understand the pharmacology and probably also the physiological regulation of
      growth hormone (GH) secretion, an important finding was that GHRP increased
      pulsatile GH secretion in children as well as normal younger and older men and
      women. This requires endogenous GHRH secretion, even though GHRP alone
      substantially releases GH from the pituitary in vitro without the addition of
      GHRH. Unnatural GHRP gave rise to natural GHRP ghrelin because of many talented
      researchers worldwide. GHRP was first envisioned to be an analog of GHRH but,
      from comparison of the activity of GHRH and GHRPs between 1982 and1984, it was
      hypothesized to reflect the activity of a new hormone regulator of GH secretion
      yet to be isolated and identified. Intravenous bolus GHRP releases more GH than
      GHRH in humans, but the reverse occurs in vitro. GHRPs are pleiotropic peptides
      with major effects on GH, nutrition, and metabolism, especially as an additional
      hormone in combination with GHRH as a new regulator of pulsatile GH secretion.
      The first indication of pleiotropism was an increase of food intake by GHRP. A
      major reason for the prolonged initial interest in the GHRPs has been its
      similar, yet different and complementary, action with GHRH on GH regulation and
      secretion. Particularly noteworthy is the variable chemistry of the GHRPs. They
      consist of three major chemical classes, including peptides, partial peptides,
      and nonpeptides, and all probably act via the same receptor and cellular
      mechanisms. Generally, most GHRPs have been active by all routes of
      administration, intravenously (iv), subcutaneously (sc), orally, intranasally,
      and intracerebroventricularly (icv), which supports their possible broad future
      clinical utility. From evolutionary studies starting with the zebrafish, the
      natural receptor and hormone have been present for hundreds of years,
      underscoring the fundamental evolutionary and functional importance of the
      ghrelin system. GHRPs were well established to act directly on both the
      hypothalamus and pituitary several years before the GHS receptor assay (Howard et
      al., 1996; Smith et al., 1996; Van der Ploeg et al., 1998). Finally, the ghrelin
      chemical isolation and identification was accomplished surprisingly from the
      stomach, which is the major site but not the only site, for example, the
      hypothalamus (Bowers, 2005; Kojima et al., 1999; Sato et al., 2005). Ghrelin was
      isolated and identified by Kojima and Kangawa et al. in 1999. A primary action of
      GHRPs continues to concern GH secretion and regulation, but increasingly this has
      included direct and indirect effects on nutrition and metabolism as well as a
      variety of other actions which may be pharmacological and/or physiological.
      Possible continuing and expanding roles of this new hormonal receptor include the
      central nervous system as well as the cardiovascular, renal, gastrointestinal,
      pancreatic, immunological, and anti-inflammatory systems. Our basic and clinical
      studies have mainly involved effects on GH regulation and secretion and this
      relationship to metabolism. So far in our studies, the actions of GHRPs and
      ghrelin on GH secretion and regulation in rats and probably in humans have
      generally been the same. A current objective is the incorporation of ghrelin into
      the diffuse endocrine hormonal system especially via GH.

PMID- 22975044
TI  - Orphan GPCRs and methods for identifying their ligands.
AB  - G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface
      receptors. These proteins play a crucial role in physiology by facilitating cell
      communication through recognition of diverse ligands, including bioactive
      peptides, amines, nucleosides, and lipids. The human genome sequencing project
      identified more than 100 orphan GPCRs, whose ligands had not yet been discovered.
      We subsequently identified ghrelin, neuromedin U, and neuromedin S as endogenous
      ligands of various orphan GPCRs and have proposed various mechanisms through
      which these peptides regulate physiological functions through their cognate
      GPCRs. In this chapter, we review methods for identifying novel peptide ligands
      of orphan GPCRs.

PMID- 22975045
TI  - Purification of rat and human ghrelins.
AB  - Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate
      the release of growth hormone (GH) from the pituitary. They act through the GHS
      R, a G-protein-coupled receptor highly expressed in the hypothalamus and
      pituitary. Using an orphan receptor strategy with a stable cell line expressing
      GHS-R, we purified endogenous ligands for GHS-R from rat and human stomach and
      named it "ghrelin," after a word root (ghre) in Proto-Indo-European languages
      meaning "grow." Ghrelin is a peptide hormone in which the third amino acid,
      usually a serine but in some species a threonine, is modified by a fatty acid;
      this modification is essential for ghrelin's activity. The main active form of
      rat ghrelin is 28-amino acid peptides with n-octanoyl modification. In rat
      stomach, a second type of ghrelin peptide was purified, identified as des-Gln14
      ghrelin. With the exception of the deletion of Gln14, des-Gln14-ghrelin is
      identical to ghrelin, retaining the n-octanoic acid modification. Des-Gln14
      ghrelin is encoded by an mRNA created by alternative splicing of the ghrelin
      gene. As in the rat, the major active form of human ghrelin is a 28-amino acid
      peptide with an n-octanoylated Ser3. However, in human stomach, several minor
      forms of human ghrelin peptides have been isolated. These can be classified into
      four groups by the type of acylation observed at Ser3 and into two groups by the
      amino acids in length. The discovery of ghrelin indicates that the release of GH
      from the pituitary and appetite stimulation might be regulated by ghrelin derived
      from the stomach.

PMID- 22975046
TI  - Variety of acyl modifications in mammalian ghrelins.
AB  - Ghrelin, a 28-amino acid-long peptide with an n-octanoyl modification at Ser(3),
      has been isolated from rat and human stomachs as an endogenous ligand for the
      growth hormone secretagogue receptor. It is very important to study the ghrelin
      from mammals (especially, domestic animals) that serve as human companions, food
      resources, and model organisms. We purified feline and caprine ghrelin and
      observed that the administration of synthetic ghrelin increased plasma growth
      hormone (GH) levels in cats and goats. Therefore, we believe that ghrelin may
      play important roles in GH release in mammals.

PMID- 22975047
TI  - Determination of nonmammalian ghrelin.
AB  - Ghrelin is a peptide with a unique molecular modification by a fatty acid such as
      n-octanoic acid. The acyl modification is necessary for ghrelin to bind to its
      receptor (growth hormone secretagogue-receptor 1a, GHS-R1a) and to induce
      subsequent intracellular Ca(2+) signaling. Ghrelin is widely expressed in mammals
      as well as in nonmammalian vertebrates. In our laboratory, a method for efficient
      purification of ghrelin from a small amount of tissues has been established.
      Here, we introduce the identification process of ghrelin in nonmammalian
      vertebrates.

PMID- 22975048
TI  - Morphological analysis of ghrelin neurons in the hypothalamus.
AB  - Ghrelin, which is mainly produced in the A/X-like cells of the oxyntic glands of
      the stomach, transduces an appetite-stimulatory signal from peripheral tissues to
      the central nervous system. Ghrelin is also localized in the hypothalamic arcuate
      nucleus of rodents. While ghrelin acts on the hypothalamus to promote feeding
      behavior and energy metabolism, it is important to clarify the neuronal circuits
      that involve ghrelin so as to elucidate the action of ghrelin in the brain.
      Immunoelectron microscopy reveals that ghrelin neurons send synaptic outputs to
      other feeding-regulating neurons (e.g., to neurons containing orexin,
      proopiomelanocortin, or neuropeptide Y) and receive synaptic inputs from other
      feeding-regulating neurons (proopiomelanocortin or neuropeptide Y). This chapter
      describes the immunohistochemical techniques employed to elucidate the neuronal
      interactions between ghrelin and other kinds of feeding-regulating peptide
      containing neurons in the hypothalamus based on evidence at both light
      microscopic and ultrastructural levels.

PMID- 22975049
TI  - High-performance liquid chromatography analysis of hypothalamic ghrelin.
AB  - Ghrelin, first identified in the stomach, is a ligand of an orphan G-protein
      coupled receptor. Early studies indicated that the growth hormone secretagogue
      receptor (GHS-R; ghrelin receptor) is ubiquitously distributed in the brain. In
      addition, centrally administered ghrelin and ghrelin receptor agonist have
      effects on central neurons in many regions, including the hypothalamus, caudal
      brain stem, and spinal cord. These effects are due to ghrelin secreted from the
      brain, rather than from the stomach; ghrelin does not cross efficiently through
      the blood-brain barrier. Identification of ghrelin in the hypothalamus
      demonstrated that, as with stomach ghrelin, hypothalamic ghrelin also has two
      molecular forms, namely, octanoyl ghrelin and des-acyl ghrelin. Hypothalamic
      ghrelin plays diverse roles in processes including feeding regulation and
      thermoregulation. Thus, the analysis of hypothalamic ghrelin will provide new
      information about the action of ghrelin in the central nervous system. In this
      chapter, we outline high-performance liquid chromatography and real-time PCR
      analysis of hypothalamic ghrelin.

PMID- 22975050
TI  - Standard sample collections for blood ghrelin measurements.
AB  - BACKGROUND: Octanoyl modification of ghrelin is rapidly hydrolyzed to des-acyl
      ghrelin in blood samples. Owing to the increased interest in ghrelin measurement,
      a standardized method of sample collection is required. METHODS: This chapter
      investigates the effect of a variety of anticoagulants and storage conditions on
      ghrelin stability. Experiment 1 evaluates the effects of anticoagulants on
      ghrelin measurements. Experiment 2 evaluates the effect of plasma pH on ghrelin
      stability. Experiment 3 evaluates the mechanisms of degradation of the active
      form of ghrelin in plasma. Experiment 4 investigates the kinetics of ghrelin
      following intravenous injection of rat ghrelin. RESULTS: In whole blood and
      plasma, octanoylated ghrelin is highly unstable. The collection of blood samples
      with EDTA-aprotinin under cooled conditions was appropriate to maintain ghrelin
      stability. Acidification of plasma to pH 3-4 and storage at 4 degrees C
      maintained ghrelin stability. The degradation of ghrelin was shown to be due to
      the hydrolysis to des-acyl ghrelin. After intravenous administration to rats,
      plasma ghrelin levels rapidly decreased with a half-life of 8 min. CONCLUSION:
      The results showed that the ghrelin values measured in human blood samples were
      markedly affected by the conditions of collection and storage, the pH, and the
      RIA method in measurement. Measuring the ghrelin values of the active form is
      useful for studying plasma ghrelin changes over short time periods. As ghrelin is
      highly unstable, it is necessary to standardize the preparation of samples to
      ensure reliable ghrelin measurements.

PMID- 22975052
TI  - Enzymatic characterization of GOAT, ghrelin O-acyltransferase.
AB  - Ghrelin is a gastric peptide hormone in which serine 3 (threonine 3 in frogs) is
      modified primarily by an n-octanoic acid; this modification is essential for
      ghrelin's activity. The enzyme that transfers n-octanoic acid to the third serine
      residue of ghrelin peptide has been identified and named GOAT for ghrelin O
      acyltransferase. GOAT is the only known enzyme that catalyzes the acyl
      modification of ghrelin and specifically modifies the third amino acid serine and
      does not modify other serine residues in ghrelin peptides. GOAT prefers n
      hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach n
      octanoyl form is the main acyl-modified ghrelin and the concentration of n
      hexanoyl form is very low. Moreover, a four-amino acid peptide derived from the N
      terminal sequence of ghrelin can be modified by GOAT, indicating that these four
      amino acids constitute the core motif for substrate recognition by the enzyme.

PMID- 22975051
TI  - From ghrelin to ghrelin's O-acyl transferase.
AB  - The hormone ghrelin is a unique signaling peptide with powerful metabolic
      effects, mediated by its acylated forms. The acyl modification of ghrelin is
      unique in that it takes place via a susceptible ester linkage in the conserved
      serine-3 of ghrelin and is composed principally of octanoyl and, to lesser
      extent, decanoyl fatty acids. The nature of this ester linkage makes it
      susceptible to esterases, which convert it to its des-acyl forms, and, if not
      adequately inhibited, the conversion to des-acyl ghrelin, particularly post
      sample collection, can lead to artifactual and misleading results. Here, we
      describe sample processing and mass spectrometric methodologies for the accurate
      and simultaneous quantification of acylated and des-acylated forms of ghrelin. We
      exploited these methodologies (1) to characterize circulating and tissue-specific
      forms of acyl and des-acyl ghrelin, (2) to optimize a cell system for acyl
      ghrelin production and search for the enzyme responsible for ghrelin's acylation,
      and (3) to demonstrate that GOAT is ghrelin's O-acyl transferase.

PMID- 22975053
TI  - The study of ghrelin deacylation enzymes.
AB  - Like other posttranslational modifications, fatty acid modification of amino acid
      residues in peptide chains is a critical determinant of their functional
      properties. A unique feature of ghrelin is the attachment of an acyl moiety at
      the third serine residue. Ghrelin is a hormone present in the circulation with
      roles in the release of growth hormone, control of behaviors related to appetite,
      and diverse cellular functions. Although lipid modification of ghrelin is
      essential for its binding to the ghrelin receptor, several lines of evidence
      suggest that deacylated ghrelin has physiological activity or activities similar
      to and distinct from the activities of the acylated form. Therefore, the
      understanding of deacylating process of ghrelin in vivo is key to accepting the
      physiological importance of ghrelin. In this review, we summarize results and
      methodology relevant to our recent efforts to determine the molecular mechanisms
      involved in ghrelin processing, including (1) immunological and mass spectrometry
      based detection of ghrelin, (2) quantification of ghrelin deacylase activity, and
      (3) characterization of ghrelin deacylation enzymes isolated from biological
      fluids and using heterologous expression systems.

PMID- 22975054
TI  - Synthesis of ghrelin: chemical synthesis and semisynthesis for large-scale
      preparation of modified peptides.
AB  - Most biologically active peptide hormones, including ghrelin, undergo numerous
      posttranslational modifications and play many crucial roles in nature. Medium- or
      large-scale preparation methods are required to understand their biological
      functions and potential applications in life sciences and the biomedical fields.
      Since ghrelin has an O-acyl modification in its Ser3, recombinant expression for
      its production has not solely been employed thus far. In this chapter, we provide
      two distinct protocols for the preparation of human ghrelin: a chemical synthesis
      method for medium-scale (up to hundreds of milligrams) and a semisynthesis method
      for large-scale (more than grams) preparation. Established Fmoc chemistry for
      solid-phase synthesis enables the highly efficient procedure for synthesizing
      ghrelin in the medium scale. Semisynthesis method, the coupling of chemically
      synthesized O-acylated ghrelin(1-7) with recombinantly expressed ghrelin(8-28),
      can be applied for larger scale preparation.

PMID- 22975057
TI  - Ghrelin in the control of energy, lipid, and glucose metabolism.
AB  - The discovery of ghrelin as the endogenous ligand for the growth hormone
      secretagogue receptor (GHS-R) led to subsequent studies characterizing the
      endogenous action of this gastrointestinal hormone. Accordingly, exogenous
      administration of ghrelin was found to increase food intake and adiposity in a
      variety of species, including rodents, nonhuman primates, and humans. Later work
      supported these findings and confirmed that ghrelin acts through hypothalamic
      neurons to mediate its effects on energy metabolism. Ghrelin acts specifically
      through GHS-R to promote a positive energy balance as demonstrated by loss of
      ghrelin action after pharmacological blockade or genetic deletion of GHS-R. More
      recently, ghrelin was found to be a mediator of glucose metabolism and acts to
      inhibit insulin secretion from pancreatic beta-cells. Together, the literature
      highlights a predominant role of ghrelin in regulating energy and glucose
      metabolism.

PMID- 22975056
TI  - Model-based evaluation of growth hormone secretion.
AB  - A minimal-model framework is that growth hormone (GH) secretion is controlled by
      an ensemble of interlinked peptides, namely, GH-releasing hormone (GHRH),
      somatostatin (SS), and ghrelin. Clinical studies, laboratory experiments, rare
      sporadic mutations, targeted gene silencing, and biomathematical models establish
      that at least three signals regulate GH secretion. A clarion implication of the
      concept of integrative control is that no one peptidic effector operates alone or
      can be adequately studied alone. A major unanswered question is how
      pathophysiology disrupts the core regulatory ensemble, thereby forcing relative
      GH and IGF-1 deficiency or excess. However, salient technical hurdles exist,
      namely, the lack of reliable experimental strategies and the paucity of validated
      analytical tools to distinguish the interlinked roles of GHRH, SS, and ghrelin.
      To address these significant obstacles requires administering peptide
      secretagogues in distinct combinations akin to the classical insulin/glucose
      clamp and implementing an analytical formalism to parse the interactive roles of
      GHRH, SS, and ghrelin objectively.

PMID- 22975058
TI  - Ghrelin and the vagus nerve.
AB  - Ghrelin, a gastrointestinal hormone, stimulates feeding and secretion of growth
      hormone (GH). Ghrelin is thought to directly affect neurons involved in feeding
      or GH secretion through growth hormone secretagogue receptor (GHS-R; ghrelin
      receptor); however, it is still unclear whether ghrelin crosses through the blood
      brain barrier. Recently, several gastrointestinal hormones have been shown to
      transmit signals involved in feeding to the brain at least in part via the vagal
      afferent system. In fact, ghrelin's action on feeding or GH secretion is
      abolished or attenuated in rats that have undergone vagotomy or treatment with
      capsaicin, a specific afferent neurotoxin. GHS-R is present in the vagal afferent
      neurons as well as the brain and is transported to the afferent terminals. In
      addition, the firing rate of vagal afferent fibers significantly decreases after
      ghrelin administration. Taken together, these data show that the vagal afferent
      system is the major pathway conveying ghrelin's signals for feeding and GH
      secretion to the brain.

PMID- 22975059
TI  - Measurement of AMP-activated protein kinase activity and expression in response
      to ghrelin.
AB  - Ghrelin is a circulating brain-gut peptide that is known to exert several
      metabolic effects such as stimulating appetite, inducing adiposity, increasing
      bone formation, and influencing the cardiovascular functions. AMP-activated
      protein kinase (AMPK), a highly conserved heterotrimeric protein that plays a key
      role in energy homeostasis, has been shown to mediate many of these metabolic
      effects of ghrelin. Ghrelin is shown to stimulate hypothalamic AMPK activity and
      inhibit liver and adipose tissue AMPK activity. The effects of ghrelin on AMPK
      activity can be studied using an elegant kinase assay, which involves
      immunoprecipitating AMPK protein from the tissue of interest followed by
      quantifying its enzymatic activity using radiolabeled adenosine triphosphate
      (ATP) in the presence of a suitable substrate. As a surrogate marker of AMPK
      activity, AMPK Thr(172) phosphorylation can be measured by Western blotting.
      Information about the AMPK pathway can also be gained by studying the mRNA
      expression of various AMPK subunits and by Western blotting for phosphorylated
      acetyl-CoA carboxylase, a key AMPK target. These methods have been widely used
      and published for investigating the effects of ghrelin on AMPK activity. In this
      chapter, we look into these experiments' methodology in detail.

PMID- 22975055
TI  - Ghrelin O-acyltransferase assays and inhibition.
AB  - Ghrelin O-acyltransferase (GOAT) is responsible for catalyzing the attachment of
      the eight-carbon fatty acid octanoyl to the Ser3 side chain of the peptide
      ghrelin to generate the active form of this metabolic hormone. As such, GOAT is
      viewed as a potential therapeutic target for the treatment of obesity and
      diabetes mellitus. Here, we review recent progress in the development of cell and
      in vitro assays to measure GOAT action and the identification of several
      synthetic GOAT inhibitors. In particular, we discuss the design, synthesis, and
      characterization of the bisubstrate analog GO-CoA-Tat and its ability to modulate
      weight and blood glucose in mice. We also highlight current challenges and future
      research directions in our biomedical understanding of this fascinating ghrelin
      processing enzyme.

PMID- 22975060
TI  - Ghrelin and gastrointestinal movement.
AB  - Ghrelin is a potent stimulant for gastric emptying and gastrointestinal (GI)
      movement. Clinically, it has been reported that the intravenous administration of
      ghrelin accelerates the rate of gastric emptying and induces gastric phase III
      contractions of the migrating motor complex in healthy volunteers. Recent
      technical advances in the measurement of GI motility in conscious small animals,
      including rats, mice, and the house musk shrew (Suncus murinus), have helped to
      elucidate the precise mechanism of action of ghrelin. Intravenous administration
      of ghrelin induces fasted motor activities with phase III-like contractions of
      the migrating motor complex in the antrum and duodenum in animals. These effects
      of ghrelin are mediated by activating the hypothalamic orexigenic neuropeptide Y
      neuron through ghrelin receptors located at the vagal afferent terminal. Stress
      hormone and anorexigenic peptides cause the disruption of fasted motor activity
      and induce fed-like motor activity. Ghrelin and the ghrelin signal potentiator
      rikkunshito successfully restore fed-like motor activities to fasted activities
      in fenfluramine-treated rats and in a cancer anorexia-cachexia animal model.
      These findings suggest that ghrelin can be expected to be a therapeutic target
      for GI disorders.

PMID- 22975061
TI  - Ghrelin acylation by ingestion of medium-chain fatty acids.
AB  - We found in a primary study that ingestion of medium-chain fatty acids (MCFAs) or
      medium-chain triacylglycerols (MCTs) increased the stomach contents of acyl
      ghrelin, and we further showed that the carbon-chain length of the acyl groups
      that modified the nascent ghrelin peptides corresponded to that of the ingested
      MCFAs or MCTs. These findings clearly demonstrated that the ingested MCFAs are
      directly used for the acyl-modification of ghrelin. Before the discovery of
      ghrelin-O-acyltransferase (GOAT), our in vivo study suggested that the putative
      GOAT preferred MCTs (composed of C6:0 to C10:0 FFAs) to either short- or long
      chain triglycerides. In another study, we suggested that MCFAs or MCTs might
      represent a potential therapeutic modality for the clinical manipulation of
      energy metabolism through the modulation of ghrelin activity. After the discovery
      of GOAT, many studies have been done on the acylation of ghrelin using MCFAs,
      MCTs, or their derivatives; however, results and interpretations have been
      inconsistent, largely due to the differences in experimental conditions. This
      chapter describes detailed methods for the analysis of ghrelin acylation in vivo
      to facilitate future research in this field.

PMID- 22975062
TI  - Islet beta-cell ghrelin signaling for inhibition of insulin secretion.
AB  - Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach, where
      circulating ghrelin is produced predominantly. In addition to its unique role in
      regulating growth-hormone release, mealtime hunger, lipid metabolism, and the
      cardiovascular system, ghrelin is involved in the regulation of glucose
      metabolism. Ghrelin is expressed in pancreatic islets and released into
      pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats, and
      humans. Pharmacological and genetic blockades of islet-derived ghrelin markedly
      augment glucose-induced insulin release. The signal transduction mechanisms of
      ghrelin in islet beta-cells are very unique, being distinct from those utilized
      for growth-hormone release. Ghrelin attenuates the glucose-induced cAMP
      production and PKA activation, which drives activation of Kv channels and
      suppression of the glucose-induced [Ca(2+)](i) increase and insulin release in
      beta-cells. Insulinostatic function of the ghrelin-GHS-R system in islets is a
      potential therapeutic target for type 2 diabetes.

PMID- 22975063
TI  - Rikkunshito as a ghrelin enhancer.
AB  - Rikkunshito is a kampo herbal medicine which is widely used in Japan for the
      treatment of the upper gastrointestinal symptoms of patients with functional
      dyspepsia, gastroesophageal reflux disease, dyspeptic symptoms of
      postgastrointestinal surgery patients, and chemotherapy-induced dyspepsia in
      cancer patients. Recently, very unique characteristics of rikkunshito have been
      unveiled; oral administration of rikkunshito potentiates orexigenic action of
      ghrelin through several different mechanisms. In addition, several lines of
      evidence obtained from both animal and human studies indicate that rikkunshito
      can be an attractive and promising therapeutic option for the anorectic
      conditions including cisplatin-induced dyspepsia, anorexia of aging, stress
      induced hypophagia, and cancer cachexia-anorexia syndrome. In this chapter, we
      highlight the orexigenic effect of rikkunshito with a special focus on its
      interaction with ghrelin signaling system.

PMID- 22975064
TI  - Thermogenic characterization of ghrelin receptor null mice.
AB  - Ghrelin is the only known circulating orexigenic hormone that increases food
      intake and promotes adiposity, and these physiological functions of ghrelin are
      mediated through its receptor growth hormone secretagogue receptor (GHS-R).
      Ghrelin/GHS-R signaling plays a crucial role in energy homeostasis. Old GHS-R
      null mice exhibit a healthy phenotype-lean and insulin sensitive. Interestingly,
      the GHS-R null mice have increased energy expenditure, yet exhibit no difference
      in food intake or locomotor activity compared to wild-type mice. We have found
      that GHS-R is expressed in brown adipose tissue (BAT) of old mice. Ablation of
      GHS-R attenuates age-associated decline in thermogenesis, exhibiting a higher
      core body temperature. Indeed, the BAT of old GHS-R null mice reveals enhanced
      thermogenic capacity, which is consistent with the gene expression profile of
      increases in glucose/lipid uptake, lipogenesis, and lipolysis in BAT. The data
      collectively suggest that ghrelin/GHS-R signaling has important roles in
      thermogenesis. The recent discovery that BAT also regulates energy homeostasis in
      adult humans makes the BAT a new antiobesity target. Understanding the roles and
      molecular mechanisms of ghrelin/GHS-R in thermogenesis is of great significance.
      GHS-R antagonists might be a novel means of combating obesity by shifting
      adiposity balance from obesogenesis to thermogenesis.

PMID- 22975065
TI  - Transgenic mice overexpressing ghrelin or ghrelin analog.
AB  - To understand the chronic effects of ghrelin, genetically engineered mouse models
      would be useful. Early studies, however, suggested that it was challenging to
      generate ghrelin gain-of-activity models by standard procedures. Although several
      groups have been trying to generate transgenic (Tg) mice overexpressing ghrelin,
      almost all these animals produced only des-acyl ghrelin rather than acylated
      ghrelin. Therefore, to elucidate the mechanism for the fatty acid modification in
      ghrelin, many researchers have been seeking an enzyme that would catalyze the
      acylation of ghrelin with an octanoic acid. In 2008, ghrelin O-acyltransferase
      (GOAT) was identified at last, and thereafter double-Tg mice overexpressing
      ghrelin and GOAT were generated by Kirchner et al. On the other hand, we have
      succeeded in generating Tg mice overexpressing Trp(3)-ghrelin, a ghrelin analog
      that does not require posttranscriptional modification with GOAT for activity.
      These ghrelin gain-of-activity models are useful tools for evaluating the long
      term pathophysiological and/or pharmacological effects of ghrelin or ghrelin
      analogs and provide insight into the physiological roles of ghrelin/GHS-R
      systems.

PMID- 22975066
TI  - Therapeutic potential of ghrelin in restricting-type anorexia nervosa.
AB  - Anorexia nervosa (AN) is an eating disorder characterized by a decrease in
      caloric intake and malnutrition. It is associated with a variety of medical
      morbidities as well as significant mortality. Nutritional support is of paramount
      importance to prevent impaired quality of life later in life in affected
      patients. Some patients with restricting-type AN who are fully motivated to gain
      body weight cannot increase their food intake because of malnutrition-induced
      gastrointestinal dysfunction. Chronicity of AN prevents participation in social
      activities and leads to increased medical expenses. Therefore, there is a
      pressing need for effective appetite-stimulating therapies for patients with AN.
      Ghrelin is the only orexigenic hormone that can be given intravenously.
      Intravenous infusion of ghrelin is reported to increase food intake and body
      weight in healthy subjects as well as in patients with poor nutritional status.
      Here, we introduce the results of a pilot study that investigated the effects of
      ghrelin on appetite, energy intake, and nutritional parameters in five patients
      with restricting-type AN, who are fully motivated to gain body weight but could
      not increase their food intake because of malnutrition-induced gastrointestinal
      dysfunction.

PMID- 22975067
TI  - Clinical application of ghrelin for chronic respiratory diseases.
AB  - The discovery of ghrelin has resulted in the development of potential
      therapeutics for cachexia caused by multiple underlying diseases. When chronic
      respiratory diseases progress to their advanced stages, cachexia often occurs,
      thereby worsening the patient's prognosis. A small clinical trial that enrolled
      cachectic patients with chronic respiratory disease revealed that administration
      of ghrelin improved their nutritional status and exercise tolerance. Short-term
      administration of ghrelin was found to be safe and tolerated with adverse events,
      including suffusion, sleepiness, peristalsis, hunger, and sweating. Further large
      scale and long-term clinical trials are needed.

PMID- 22975068
TI  - Clinical trial of ghrelin synthesis administration for upper GI surgery.
AB  - Appetite and weight loss following gastrectomy or esophagectomy is one of the
      major problems that affect the postoperative QoL. Ghrelin, mainly secreted from
      the stomach, is related to appetite, weight gain, and positive energy balance.
      This hormone level had been shown to become low for a long time after upper GI
      surgery. The efficacy of ghrelin synthesis administration for postoperative
      weight loss was investigated from a clinical trial to develop a new strategy for
      weight gain. In addition to this treatment for appetite and weight loss, we
      focused on the anti-inflammatory role of ghrelin. For the purpose of controlling
      postoperative cytokine storm after esophagectomy, this hormone was introduced in
      the clinical trial. Finally, ghrelin replacement therapy during chemotherapy in
      patients with esophageal cancer is also presented. Our clinical trials and their
      results are presented in this chapter.

PMID- 22975069
TI  - Methods in Enzymology. Ghrelin. Preface.

PMID- 22975071
TI  - Bismuth iodoform paraffin paste: a review.

PMID- 22975072
TI  - Getting a grip on the terminator.

PMID- 22975070
TI  - Reproducibility of four-dimensional computed tomography-based lung ventilation
      imaging.
AB  - RATIONALE AND OBJECTIVES: A novel ventilation imaging method based on four
      dimensional (4D) computed tomography (CT) has been applied to the field of
      radiation oncology. Understanding its reproducibility is a prerequisite for
      clinical applications. The purpose of this study was to quantify the
      reproducibility of 4D CT ventilation imaging over different days and the same
      session. MATERIALS AND METHODS: Two ventilation images were created from repeat
      4D CT scans acquired over the average time frames of 15 days for 6 lung cancer
      patients and 5 minutes for another 6 patients. The reproducibility was quantified
      using the voxel-based Spearman rank correlation coefficients for all lung voxels
      and Dice similarity coefficients (DSC) for the spatial overlap of segmented high
      , moderate-, and low-functional lung volumes. Furthermore, the relationship
      between the variation in abdominal motion range as a measure of the depth of
      breathing and variation in ventilation was evaluated using linear regression.
      RESULTS: The voxel-based correlation between the two ventilation images was
      moderate on average (0.50 +/- 0.15). The DSCs were also moderate for the high-
      (0.60 +/- 0.08), moderate- (0.46 +/- 0.06), and low-functional lung (0.58 +/-
      0.09). No patients demonstrated strong correlations. The relationship between the
      motion range variation and ventilation variation was found to be moderate and
      significant. CONCLUSIONS: We investigated the reproducibility of 4D CT
      ventilation imaging over the time frames of 15 days and 5 minutes and found that
      it was only moderately reproducible. Respiratory variation during 4D CT scans was
      found to deteriorate the reproducibility. Improvement of 4D CT imaging is
      necessary to increase the reproducibility of 4D CT ventilation imaging.

PMID- 22975073
TI  - Improving sleep with mindfulness and acceptance: a metacognitive model of
      insomnia.
AB  - While there is an accumulating evidence to suggest that therapies using
      mindfulness and acceptance-based approaches have benefits for improving the
      symptoms of insomnia, it is unclear how these treatments work. The goal of this
      paper is to present a conceptual framework for the cognitive mechanisms of
      insomnia based upon mindfulness and acceptance approaches. The existing cognitive
      and behavioral models of insomnia are first reviewed and a two-level model of
      cognitive (primary) and metacognitive (secondary) arousal is presented in the
      context of insomnia. We then focus on the role of metacognition in mindfulness
      and acceptance-based therapies, followed by a review of these therapies in the
      treatment of insomnia. A conceptual framework is presented detailing the
      mechanisms of metacognition in the context of insomnia treatments. This model
      proposes that increasing awareness of the mental and physical states that are
      present when experiencing insomnia symptoms and then learning how to shift mental
      processes can promote an adaptive stance to one's response to these symptoms.
      These metacognitive processes are characterized by balanced appraisals, cognitive
      flexibility, equanimity, and commitment to values and are posited to reduce sleep
      related arousal, leading to remission from insomnia. We hope that this model will
      further the understanding and impact of mindfulness and acceptance-based
      approaches to insomnia.

PMID- 22975074
TI  - Mycoplasma genitalium, an emerging sexually transmitted pathogen.
AB  - Mycoplasma genitalium is a sexually transmitted organism associated with non
      gonococcal urethritis in men and several inflammatory reproductive tract
      syndromes in women such as cervicitis, pelvic inflammatory disease, and
      infertility. There was evidence for an association of M. genitalium with
      endometritis and pelvic inflammatory disease (PID), but additional studies are
      necessary to confirm this. The evidence as to whether M. genitalium can cause
      adverse pregnancy outcomes such as preterm labor is conflicting. But the authors
      of some studies on M. genitalium as a cause of infertility have reported this
      association. This species is very difficult to culture; thus, nucleic acid
      amplification testing is the only method available for M. genitalium detection.
      The lack of a cell wall makes M. genitalium intrinsically resistant to
      antibiotics acting at this level, such as beta-lactams. The treatment of M.
      genitalium infections is not standardized. Macrolides are recommended, especially
      single-dose azithromycin; tetracyclines are responsible for a great number of
      therapeutic failures even no resistance mechanism has yet been demonstrated.
      Acquired resistance to macrolides and fluoroquinolones leading to therapeutic
      failure has also been reported. All this raises the issue of the most appropriate
      therapeutic management and requires drafting diagnostic and therapeutic
      guidelines for the treatment of M. genitalium infections.

PMID- 22975075
TI  - Outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae in
      an intensive care unit (Brest).
AB  - INTRODUCTION: We had for aim to describe control and investigation of an outbreak
      caused by a strain of Extended spectrum beta-lactamase producing Klebsiella
      pneumoniae in intensive care units of the Brest teaching hospital. PATIENTS AND
      METHOD: The case definition was a patient infected by or carrying the epidemic
      strain. Control measures and investigations are presented. A case-control study
      was conducted in the surgical intensive care unit. Each case was matched with two
      controls based on admission times in the unit. The study focused on diagnostic
      and therapeutic procedures, and potential contacts with healthcare workers, in
      this context of cross transmission. RESULTS: Between February and May 2011, nine
      cases were reported in the surgical ICU and two in the medical ICU. Eighteen
      controls were matched with the nine surgical ICU cases. Several factors were
      found to be statistically associated with infection or colonization by the
      epidemic strain: the surgical block in which patients had been operated and the
      ward of first hospitalization; the number of trans-esophageal and trans-thoracic
      echocardiographies, of central venous catheter insertions, and of surgical
      operations; intubation. The total number of invasive procedures was also found to
      be statistically higher among cases. CONCLUSION: This study identified factors
      associated with colonization or infection by the epidemic strain. These factors
      might have been involved in the transmission tree, and be vulnerable elements for
      the prevention of nosocomial infections and colonisations, and their epidemic
      spread.

PMID- 22975076
TI  - ZBRK1 represses HIV-1 LTR-mediated transcription.
AB  - The identification of cellular proteins that interact with the human
      immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) provides a basic
      understanding of HIV-1 gene expression, which is the major determinant regulating
      virus replication. We show that ZBRK1 negatively regulates the HIV-1 LTR. Ectopic
      expression of ZBRK1 represses transcriptional activity of the HIV-1 LTR, whereas
      the depletion of endogenous ZBRK1 leads to activation of the HIV-1 LTR. The
      repressor activity of ZBRK1 is required for TRIM28 binding. Furthermore, ZBRK1 is
      bound to the HIV-1 LTR in vivo. These results indicate that ZBRK1 could be
      involved in a potent intrinsic antiretroviral defense.

PMID- 22975077
TI  - Evaluation of qPCR curve analysis methods for reliable biomarker discovery: bias,
      resolution, precision, and implications.
AB  - RNA transcripts such as mRNA or microRNA are frequently used as biomarkers to
      determine disease state or response to therapy. Reverse transcription (RT) in
      combination with quantitative PCR (qPCR) has become the method of choice to
      quantify small amounts of such RNA molecules. In parallel with the
      democratization of RT-qPCR and its increasing use in biomedical research or
      biomarker discovery, we witnessed a growth in the number of gene expression data
      analysis methods. Most of these methods are based on the principle that the
      position of the amplification curve with respect to the cycle-axis is a measure
      for the initial target quantity: the later the curve, the lower the target
      quantity. However, most methods differ in the mathematical algorithms used to
      determine this position, as well as in the way the efficiency of the PCR reaction
      (the fold increase of product per cycle) is determined and applied in the
      calculations. Moreover, there is dispute about whether the PCR efficiency is
      constant or continuously decreasing. Together this has lead to the development of
      different methods to analyze amplification curves. In published comparisons of
      these methods, available algorithms were typically applied in a restricted or
      outdated way, which does not do them justice. Therefore, we aimed at development
      of a framework for robust and unbiased assessment of curve analysis performance
      whereby various publicly available curve analysis methods were thoroughly
      compared using a previously published large clinical data set (Vermeulen et al.,
      2009) [11]. The original developers of these methods applied their algorithms and
      are co-author on this study. We assessed the curve analysis methods' impact on
      transcriptional biomarker identification in terms of expression level,
      statistical significance, and patient-classification accuracy. The concentration
      series per gene, together with data sets from unpublished technical performance
      experiments, were analyzed in order to assess the algorithms' precision, bias,
      and resolution. While large differences exist between methods when considering
      the technical performance experiments, most methods perform relatively well on
      the biomarker data. The data and the analysis results per method are made
      available to serve as benchmark for further development and evaluation of qPCR
      curve analysis methods (http://qPCRDataMethods.hfrc.nl).

PMID- 22975078
TI  - Activation of Akt through 5-HT2A receptor ameliorates serotonin-induced
      degradation of insulin receptor substrate-1 in adipocytes.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) was found to be elevated in the serum of
      diabetic patients. In this study, we investigate the mechanism of insulin
      desensitization caused by 5-HT. In 3T3-L1 adipocytes, 5-HT treatment induced the
      translocation of insulin receptor substrate-1 (IRS-1) from low density microsome
      (LDM), the important intracellular compartment for its functions, to cytosol,
      inducing IRS-1 ubiquitination and degradation. Moreover, inhibition of 5-HT
      stimulated Akt activation by either ketanserin (a specific 5-HT2A receptor
      antagonist) or knocking-down the expression of 5-HT2A receptor promoted 5-HT
      stimulated IRS-1 dissociation from 14-3-3beta in LDM, leading to drastic
      ubiquitination. Interestingly, sarpogrelate, another antagonist of 5-HT2A
      receptor, protected IRS-1 from degradation through activation of Akt. This
      implicates the importance of Akt activation in extending IRS-1 life span through
      maintaining their optimal sub-location into adipocytes. Taken together, this
      study suggest that activation of Akt may be able to compensate the adverse
      effects of 5-HT by stabilizing IRS-1 in LDM.

PMID- 22975080
TI  - Altered lung function relates to inflammation in an acute LPS mouse model.
AB  - Preclinical in vivo models of lipopolysaccharide (LPS) -induced acute lung injury
      are commonly used to recapitulate pathophysiological features of chronic
      obstructive pulmonary disease and acute exacerbations. The LPS-induced lung
      inflammation is well described; however, whether the inflammatory response
      relates temporally to specific alterations in lung function has not been
      elucidated. We have investigated the effects of acute LPS inhalation in mice up
      to 96 h post LPS. Quantitation of inflammatory cells and inflammatory mediators
      in bronchoalveolar lavage fluid and non-invasive and invasive lung function
      measurements were performed at corresponding time points. The inhibitory effect
      of the glucocorticoid, budesonide, on LPS-induced lung inflammation and lung
      function was determined. LPS inhalation induced distinct histopathological
      changes, and infiltration of inflammatory cells to the lungs peaked at 48 h. At
      this time point, significantly increased inflammatory mediators and significantly
      altered lung capacity and mechanics parameters were observed. Budesonide given
      per os prevented the LPS-induced lung inflammation and lung dysfunction. These
      results demonstrate a temporal relationship between the peak of inflammatory cell
      influx and significant impairment of lung function, suggestive of a causative
      role of inflammation. These results allow better understanding of the functional
      consequences of lung inflammation in respiratory diseases.

PMID- 22975079
TI  - Identification of endocrine disrupting chemicals activating SXR-mediated
      transactivation of CYP3A and CYP7A1.
AB  - Endocrine disrupting chemicals (EDCs) have emerged as a major public health issue
      because of their potentially disruptive effects on physiological hormonal
      actions. SXR (steroid xenobiotic receptor), also known as NR1I2, regulates CYP3A
      expression in response to exogenous chemicals, such as EDCs, after binding to
      SXRE (SXR response element). In our study, luciferase assay showed that 14 out of
      55 EDCs could enhance SXR-mediated rat or human CYP3A gene transcription nearly
      evenly, and could also activate rat CYP7A1 gene transcription by cross
      interaction of SXR and LXRE (LXRalpha response element). SXR diffused in the
      nucleus without ligand, whereas intranuclear foci of liganded SXR were produced.
      Furthermore, endogenous mRNA expression of CYP3A4 gene was enhanced by the 14
      positive EDCs. Our results suggested a probable mechanism of EDCs disrupting the
      steroid or xenobiotic metabolism homeostasis via SXR.

PMID- 22975081
TI  - Crossmodal object recognition in rats with and without multimodal object pre
      exposure: no effect of hippocampal lesions.
AB  - The neural mechanisms and brain circuitry involved in the formation, storage, and
      utilization of multisensory object representations are poorly understood. We have
      recently introduced a crossmodal object recognition (CMOR) task that enables the
      study of such questions in rats. Our previous research has indicated that the
      perirhinal and posterior parietal cortices functionally interact to mediate
      spontaneous (tactile-to-visual) CMOR performance in rats; however, it remains to
      be seen whether other brain regions, particularly those receiving polymodal
      sensory inputs, contribute to this cognitive function. In the current study, we
      assessed the potential contribution of one such polymodal region, the hippocampus
      (HPC), to crossmodal object recognition memory. Rats with bilateral excitotoxic
      HPC lesions were tested in two versions of crossmodal object recognition: (1) the
      original CMOR task, which requires rats to compare between a stored tactile
      object representation and visually-presented objects to discriminate the novel
      and familiar stimuli; and (2) a novel 'multimodal pre-exposure' version of the
      CMOR task (PE/CMOR), in which simultaneous exploration of the tactile and visual
      sensory features of an object 24 h prior to the sample phase enhances CMOR
      performance across longer retention delays. Hippocampus-lesioned rats performed
      normally on both crossmodal object recognition tasks, but were impaired on a
      radial arm maze test of spatial memory, demonstrating the functional
      effectiveness of the lesions. These results strongly suggest that the HPC,
      despite its polymodal anatomical connections, is not critically involved in
      tactile-to-visual crossmodal object recognition memory.

PMID- 22975082
TI  - Cytomegalovirus pneumonia in immunocompetent host: case report and literature
      review.
AB  - CMV infection is highly prevalent in general population and its clinical picture
      generally ranges from asymptomatic disease to mononucleosis-like syndrome. While
      severe life-threatening CMV disease is well documented in certain
      immunocompromised risk groups, severe infection with symptomatic pneumonia in
      immunocompetent hosts has been rarely documented. In this paper we describe a
      case of primary CMV infection, complicated by severe CMV pneumonia in an
      immunocompetent host, successfully treated with oral valganciclovir. Moreover, we
      reviewed CMV pneumonia cases in immunocompetent adults reported in the
      literature.

PMID- 22975083
TI  - Identification of human parechovirus genotype, HPeV-12, in a paralytic child with
      diarrhea.
AB  - BACKGROUND: New genotypes of human parechoviruses have been readily identified
      after improvement of diverse diagnostic tools. We hereby report the detection of
      a new genotype, HPeV 12, from a child presented with diarrhea and paralysis.
      OBJECTIVES: The genetic variability of human parechoviruses has recently expanded
      defining 16 genotypes however data available covers only 11 genotypes. The
      present study was designed to determine the genetic characterization of human
      parechovirus identified in a child with gastroenteritis and acute flaccid
      paralysis (AFP). STUDY DESIGN: Stool samples are referred to Virology Department,
      NIH-Pakistan for the routine detection of enteroviruses and polioviruses through
      cell culture and RT-PCR. Five of isolates showing cytopathic effect on L20B cell
      line but negative for poliovirus were further explored for human parechovirus
      using multiple cell lines and RT-PCR. RESULTS: Human Coxsackie A virus type 2, 3,
      6 and 20 were found in four samples whereas the fifth sample contained human
      parechovirus genotype 12. Efficient growth of human parechovirus was found on
      L20B cells while Vero and LLC-MK2 cells showed no apparent cytopathic effect.
      CONCLUSIONS: This study describes the detection of a new human parechovirus
      genotype (HPeV-12) in a paralytic child with diarrhea. Human parechoviruses are
      now considered as potential pathogens that may cause a number of serious clinical
      complications especially in infants and young children. These findings emphasize
      to conduct large scale epidemiological surveys in the country to understand their
      association with clinical diseases especially gastroenteritis, respiratory and
      neurological disorders.

PMID- 22975084
TI  - Analytical and clinical performance characteristics of the Simplexa BK virus
      quantitative PCR assay for the diagnosis of polyomavirus-associated nephropathy
      in renal transplant recipients using plasma and urine specimens.
AB  - BACKGROUND: Polyomavirus-associated nephropathy is a significant cause of kidney
      rejection in renal transplant recipients. Quantification of BK viral load in
      plasma and urine can predict the development of polyomavirus-associated
      nephropathy, though each assay requires careful evaluation of analytical and
      clinical performance characteristics for optimal use. OBJECTIVES: This study
      evaluated the analytical and clinical performance characteristics of the Simplexa
      BK virus quantitative PCR assay. STUDY DESIGN: Analytical validation was
      performed using commercial standards, BK virus stock culture, and patient
      specimens. Clinical performance was evaluated using biopsy-proven BK nephropathy
      as the gold standard. RESULTS: The Simplexa BK virus quantitative PCR assay was
      linear over a range of 2.7-10.4 log(10) copies/mL. Limit of detection was 2.7-2.8
      log(10) copies/mL in plasma and urine samples. Sensitivities were 100% and 100%
      and specificities were 84% and 86% for plasma and urine samples, respectively,
      when compared to a reference BK assay. Clinical cutoff values of 4.0 log(10)
      copies/mL (plasma) and 7.5 log(10) copies/mL (urine) yielded 100% sensitivity and
      specificities of 87.5% and 85%, respectively, for biopsy-proven polyomavirus
      nephropathy. CONCLUSIONS: The Simplexa BK virus quantitative PCR assay has high
      sensitivity and acceptable analytical characteristics for clinical use. The
      clinical cutoff values presented here provide a rational approach to the
      monitoring and treatment of renal transplant recipients for polyomavirus
      associated nephropathy.

PMID- 22975085
TI  - Alkaline earth silicate wools - A new generation of high temperature insulation.
AB  - Intensive study of the natural asbestiform minerals that cause human diseases,
      and the consequent understanding of their hazardous characteristics, has enabled
      the development of manufactured fibres whose physical and/or chemical properties,
      in particular as they relate to biopersistence, have been adjusted to minimize
      possible harm to health. A strong driver for the developmentof new high
      temperature insulation materials wasthe perception of the toxicity of refractory
      ceramic fibres (RCF)and their classification in the EU as a category 2 carcinogen
      under Directive 67/548/EEC. Such classification carries with it the requirement
      for substitution by less hazardous materials. This paper focuses on the
      development of alkaline earth silicate (AES) wools as a new class of high
      temperature insulation with the capability of such substitution in a number of
      applications. These wools have only a low potential to cause harm because they do
      not persist in lung tissue once deposited, and have produced minimal effects in
      experimental test systems. AES wools are increasingly being used in a wide range
      of high temperature applications.

PMID- 22975087
TI  - Proteomic profiling of dog urine after European adder (Vipera berus berus)
      envenomation by two-dimensional difference gel electrophoresis.
AB  - Between April and September every year, many dogs in Finland are bitten by Vipera
      berus berus, also known as the European adder, the only venomous snake in the
      area. Exposure to snake bite venom causes local and systemic symptoms and in
      severe cases can lead to death. Urine samples were collected from four dogs
      bitten by V. berus berus and treated in the intensive care unit of the Veterinary
      Teaching Hospital at the University of Helsinki. The inclusion criteria were a
      strong suspicion of an adder bite no more than two days before admission and
      clinical signs of an adder bite. Exclusion criteria were defined as ongoing
      treatment with glucocorticoids or a known history of liver or kidney diseases.
      Six privately owned, healthy dogs were obtained as controls. Samples were
      subjected to 2D-DIGE analysis. Image analysis was performed with DeCyder 7.0 2D
      software, and protein spots demonstrating a minimum 1.5-fold difference in
      average spot volume ratios between envenomed and control dogs with a Student's t
      test p-value of less than 0.05 were picked and identified using LC-MS/MS. In 2D
      DIGE analysis, seven proteins were significantly (p < 0.05) over-expressed in the
      urine of dogs bitten by V. berus berus compared to the control group. From these,
      five proteins were identified: beta-2-microglobulin (b2MG), alpha-1-antitrypsin
      (AAT), albumin, fetuin-B and superoxide dismutase (SOD1). Results indicate that
      envenomation by V. berus berus alter the urinary protein profile in dogs.

PMID- 22975086
TI  - Randomized nutrition education intervention to improve carbohydrate counting in
      adolescents with type 1 diabetes study: is more intensive education needed?
AB  - BACKGROUND: Youth with type 1 diabetes do not count carbohydrates accurately, yet
      it is an important strategy in blood glucose control. OBJECTIVE: The study
      objective was to determine whether a nutrition education intervention would
      improve carbohydrate counting accuracy and glycemic control. DESIGN: We conducted
      a randomized, controlled nutrition intervention trial that was recruited from
      February 2009 to February 2010. SUBJECTS: Youth (12 to 18 years of age, n = 101)
      with type 1 diabetes were screened to identify those with poor carbohydrate
      counting accuracy, using a previously developed carbohydrate counting accuracy
      test covering commonly consumed foods and beverage items presented in six mixed
      meals and two snacks. All participants (n = 66, age = 15 +/- 3 years, 41 male,
      diabetes duration = 6 +/- 4 years, hemoglobin A1c [HbA1c] = 8.3% +/- 1.1%) were
      randomized to the control or intervention group at the baseline visit. The
      intervention group attended a 90-minute class with a registered
      dietitian/certified diabetes educator and twice kept 3-day food records, which
      were used to review carbohydrate counting progress. MAIN OUTCOME MEASURES:
      Carbohydrate counting accuracy (measured as described) and HbA1c were evaluated
      at baseline and 3 months to determine the effectiveness of the intervention.
      STATISTICAL ANALYSES PERFORMED: t Tests, Spearman correlations, and repeated
      measures models were used. RESULTS: At baseline, carbohydrate content was over-
      and underestimated in 16 and 5 of 29 food items, respectively. When foods were
      presented as mixed meals, participants either significantly over- or
      underestimated 10 of the 9 meals and 4 snacks. After 3 months of follow-up, HbA1c
      decreased in both the intervention and control groups by -0.19% +/- 0.12% (P =
      0.12) and -0.08% +/- 0.11% (P = 0.51), respectively; however, the overall
      intervention effect was not statistically significant for change in HbA1c or
      carbohydrate counting accuracy. CONCLUSIONS: More intensive intervention might be
      required to improve adolescents' carbohydrate counting accuracy and nutrition
      management of type 1 diabetes. Additional research is needed to translate
      nutrition education into improved health outcomes.

PMID- 22975088
TI  - Nephrotoxicity of hump-nosed pit viper (Hypnale hypnale) venom in mice is
      preventable by the paraspecific Hemato polyvalent antivenom (HPA).
AB  - Mice experimentally envenomed with Hypnale hypnale venom (1* and 1.5*LD50)
      developed acute kidney injury (AKI) principally characterized by raised blood
      urea and creatinine. Prolonged blood clotting time and hemorrhage in lungs
      implied bleeding tendency. Pallor noted in most renal cortices was suggestive of
      renal ischemia secondary to consumptive coagulopathy. Intravenous infusion of
      Hemato polyvalent antivenom following experimental envenoming effectively
      prevented death and AKI in all mice, supporting its potential therapeutic use in
      envenoming cases.

PMID- 22975089
TI  - Coupling chromosomal replication to cell growth by the initiator protein DnaA in
      Escherichia coli.
AB  - The initiation of chromosomal replication is strictly controlled during the cell
      cycle. Its frequency needs to be well-matched to the proliferation rate. In many
      bacteria, DnaA is the critical mediator in the regulation of replication
      initiation. In this work, the initiation probability is deduced based on the
      distribution of DnaA boxes at oriC in Escherichia coli. Taking into account more
      details, we develop a dynamic model to describe the oscillation of DnaA
      accompanied with the cell cycles. Our simulations show that the regulation of
      DnaA couples chromosomal replication to cell growth. We also discuss effects of
      other factors on DnaA oscillation. We propose that RNA polymerase is one of the
      candidates for harmonizing chromosomal replication and cell growth by adjusting
      dnaA transcriptional activity.

PMID- 22975090
TI  - Trypanosoma cruzi heparin-binding proteins present a flagellar membrane
      localization and serine proteinase activity.
AB  - Heparin-binding proteins (HBPs) play a key role in Trypanosoma cruzi-host cell
      interactions. HBPs recognize heparan sulfate (HS) at the host cell surface and
      are able to induce the cytoadherence and invasion of this parasite. Herein, we
      analysed the biochemical properties of the HBPs and also evaluated the expression
      and subcellular localization of HBPs in T. cruzi trypomastigotes. A flow
      cytometry analysis revealed that HBPs are highly expressed at the surface of
      trypomastigotes, and their peculiar localization mainly at the flagellar
      membrane, which is known as an important signalling domain, may enhance their
      binding to HS and elicit the parasite invasion. The plasmon surface resonance
      results demonstrated the stability of HBPs and their affinity to HS and heparin.
      Additionally, gelatinolytic activities of 70 kDa, 65.8 kDa and 59 kDa HBPs over a
      broad pH range (5.5-8.0) were revealed using a zymography assay. These
      proteolytic activities were sensitive to serine proteinase inhibitors, such as
      aprotinin and phenylmethylsulfonyl fluoride, suggesting that HBPs have the
      properties of trypsin-like proteinases.

PMID- 22975091
TI  - Label-free, nucleotide-mediated dispersion of magnetic nanoparticles for "non
      sandwich type" MRI-based quantification of enzyme.
AB  - In the present work, we demonstrate that nucleotide can adsorb efficiently on the
      surface of carboxylic acid-functionalized nanoparticles and stabilize the
      particles against aggregation. In the present study we take magnetic
      nanoparticles (MNPs), manganese oxide nanoparticles (MnO), and upconversion
      nanophosphors (UCNPs) as models. The result shows that not only MNPs, but also
      other kinds of nanoparticles that have similar surface properties can be
      dispersed and stabilized by nucleotides. Interestingly, adenosine bearing
      different numbers of phosphate groups has distinct stabilizing effect. On the
      basis of this observation, we developed a magnetic relaxation-based enzyme assay
      for quantitative analysis of alkaline phosphatase. A detection limit of 0.002
      U/MUL for calf intestine alkaline phosphatase (CIAP) could be obtained, which is
      lower than the gold nanoparticle-based colorimetric method. In contrast to the
      conventional magnetic relaxation switches (MRSw), this assay was achieved without
      covalent modification and separation steps, sandwich type binding was not
      required as well, which would potentially expand the application of magnetic
      relaxation-based analysis.

PMID- 22975092
TI  - Ultra sensitive microfluidic immunosensor for determination of clenbuterol in
      bovine hair samples using electrodeposited gold nanoparticles and magnetic micro
      particles as bio-affinity platform.
AB  - In this article, we report the first integrated microfluidic immunosensor coupled
      to a screen-printed carbon electrode (SPCE) applied to determination of
      clenbuterol (CLB) in bovine hair samples. CLB is a member of the beta(2)-agonist
      drugs which is used in animal production and is banned in Argentine and the
      European Union. It represents a potential risk and has to be carefully monitored
      to avoid the illegal use of high amounts of this compound that could result in
      human food poisoning. In order to perform the CLB detection, the SPCE was
      modified by gold nanoparticles (AuNPs) electrodeposition. Quantitative
      determination of CLB was carried out using a competitive indirect immunoassay,
      method based on the use of anti-CLB antibodies immobilized on magnetic micro
      particles. The CLB present in bovine hair samples competes immunologically with
      alkaline phosphatase (AP) enzyme-labeled CLB conjugate for the anti-CLB specific
      antibodies. Later, p-aminophenyl phosphate was converted to p-aminophenol by AP,
      and the electroactive product was quantified on AuNPs/SPCE at +0.1 V. The limit
      of detection for electrochemical method was 0.008 ng mL(-1) and the intra- and
      inter-assay coefficients of variation were below 6%. This being a veterinary
      control tool very useful for rapid, sensitive and selective detection of CLB in
      an "in vitro" technique.

PMID- 22975093
TI  - Effects of diamond-FET-based RNA aptamer sensing for detection of real sample of
      HIV-1 Tat protein.
AB  - Diamond is a promising material for merging solid-state and biological systems
      owing to its chemical stability, low background current, wide potential window
      and biocompatibility. The effects of surface charge density on human
      immunodeficiency virus type 1 Trans-activator transcription (HIV-1 Tat) protein
      binding have been investigated on a diamond field-effect transistor (FET) using
      ribonucleic acid (RNA) aptamers as a sensing element on a solid surface. A change
      in the gate potential of 91.6 mV was observed, whereby a shift in the negative
      direction was observed at a source-drain current of -8 MUA in the presence of HIV
      1 Tat protein bound to the RNA aptamers. Moreover, the reversible change in gate
      potential caused by the binding and regeneration cycles was very stable
      throughout cyclical detections. The stable immobilization is achieved via RNA
      aptamers covalently bonded to the carboxyl-terminated terephtalic acids on amine
      sites, thereby increasing the sensitivity of the HIV-1 Tat protein sensor. The
      reliable use of a real sample of HIV-1 Tat protein by an aptamer-FET was
      demonstrated for the first time, which showed the potential of diamond
      biointerfaces in clinical biosensor applications.

PMID- 22975094
TI  - The Registry of the International Society for Heart and Lung Transplantation-
      Introduction to the 2012 annual reports: new leadership, same vision.

PMID- 22975095
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      29th official adult heart transplant report--2012.

PMID- 22975096
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      fifteenth pediatric heart transplantation report--2012.

PMID- 22975097
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      29th adult lung and heart-lung transplant report-2012.

PMID- 22975098
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      fifteenth pediatric lung and heart-lung transplantation report--2012.

PMID- 22975100
TI  - Symptom burden, quality of life, and attitudes toward palliative care in patients
      with pulmonary arterial hypertension: results from a cross-sectional patient
      survey.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex disease with
      variable clinical manifestations; nevertheless, morbidity and mortality
      associated with PAH are considerable. This study examined quality of life (QOL)
      in PAH patients and assessed use of palliative care (PC) for addressing QOL
      issues and what barriers might exist regarding early PC implementation for
      patients with PAH. METHODS: An Internet-based survey was distributed to Pulmonary
      Hypertension Association patient-related listservs. Symptom burden and QOL were
      assessed using Linear Analog Self Assessment (LASA) QOL items and the Cambridge
      Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS: Of 774 eligible
      patients with active e-mail addresses, 315 returned surveys (41% overall
      response), and 276 (88%) contained analyzable responses. Responders (mean age,
      48.9 years +/- 16.0) were predominantly white (85%), female (86%), and with
      idiopathic PAH (42%). Profound deficiency in overall QOL (40%), fatigue (57%),
      physical well-being (56%), social activity (49%), emotional well-being (49%), and
      pain (38%) were reported. Most patients believed their PAH physician had
      excellent understanding of PAH progression/plan of care (92%), but less were
      satisfied with care regarding QOL management (77%). Few patients considered PC
      (8%), or had pain management (4%) or PC involved (1%). Most common reasons were
      beliefs that patients were doing well/not sick (63%) or that PC had not been
      suggested (22%). CONCLUSIONS: PAH may result in symptoms or QOL impairment
      persisting despite optimal PAH therapy. However, PC awareness or use by PAH
      patients and providers is low. Opportunities may exist to integrate PC into care
      for PAH patients.

PMID- 22975099
TI  - Relationship between mechanical and metabolic dyssynchrony with left bundle
      branch block: evaluation by 18-fluorodeoxyglucose positron emission tomography in
      patients with non-ischemic heart failure.
AB  - BACKGROUND: Ventricular dyssynchrony is a common finding in patients with heart
      failure (HF), especially in the presence of conduction delays. The loss of
      ventricular synchrony leads to progressive impairment of contractile function,
      which may be explained in part by segmental abnormalities of myocardial
      metabolism. However, the association of these metabolic disarrangements with
      parameters of ventricular dyssynchrony and electrocardiography (ECG) findings has
      not yet been studied. METHODS: Our aim was to determine the correlation between
      the presence of left bundle branch block (LBBB) with left ventricular (LV)
      mechanical synchrony assessed by multiple-gated acquisition scan (MUGA) and with
      patterns of 18-fluorodeoxyglucose (18FDG) uptake in patients with non-ischemic
      heart failure. Twenty-two patients with non-ischemic cardiomyopathy, LV ejection
      fraction (LVEF) <=45% and New York Heart Association (NYHA) Functional Class II
      or III symptoms under standard medical therapy were included, along with 10
      healthy controls matched for age and gender. A 12-lead ECG was obtained to
      measure the length of the QRS. Mechanical LV synchrony was assessed by MUGA using
      phase analysis. All patients and controls underwent positron emission tomography
      with 18FDG to determine the distribution of myocardial glucose uptake. The
      standard deviation of peak (18)FDG uptake was used as an index of metabolic
      heterogeneity. Student's t-test and Pearson's correlation were used for
      statistical analysis. RESULTS: The mean age of the patients with HF was 54 +/- 12
      years and 72% were male. The length of the QRS was 129 +/- 31 milliseconds and
      LBBB was present in 9 patients. Patients with HF had decreased LV 18FDG uptake
      compared with controls (7.56 +/- 3.36 vs. 11.63 +/- 4.55 standard uptake value; p
      = 0.03). The length of the QRS interval correlated significantly with glucose
      uptake heterogeneity (r = 0.62; p = 0.002) and mechanical dyssynchrony (r = 0.63;
      p = 0.006). HF patients with LBBB showed marked glucose uptake heterogeneity
      compared with HF patients without LBBB (41.4 +/- 10 vs 34.7 +/- 4.9 ml/100 g/min,
      respectively; p = 0.01). CONCLUSIONS: Patients with non-ischemic heart failure
      exhibit a global decrease in myocardial glucose uptake. Within this group,
      subjects who also have LBBB exhibit a marked heterogeneity in segmental glucose
      uptake, which directly correlates with QRS duration.

PMID- 22975101
TI  - HbA1c in pulmonary arterial hypertension: a marker of prognostic relevance?
AB  - BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit impaired
      glucose metabolism and increased insulin resistance. The clinical consequences of
      these metabolic changes are not known. METHODS: We assessed HbA1c levels in 115
      patients newly diagnosed with PAH (79 females and 36 males; mean age 49.2 years;
      idiopathic n = 67, collagen vascular disease n = 16, congenital heart defect n =
      19, pulmonary veno-occlusive disease n = 8, portopulmonary n = 5). No patients
      had diabetes or were receiving anti-diabetic medication or systemic steroids.
      After initiation of pulmonary vasoactive treatment, patients remained in long
      term follow-up. RESULTS: Initially, patients were in an advanced stage of disease
      (mean pulmonary arterial pressure 53 +/- 18 mm Hg, cardiac index 2.3 +/- 0.8
      liters/min/m2) with a 6-minute-walk distance of 337 +/- 123 meters, and in NYHA
      Functional Class 3.0 +/- 0.7. The HbA1c was 5.73 +/- 0.75%. A moderate but
      statistically significant positive correlation was observed between HbA1c levels
      and BNP (r(p) = 0.41, p = 0.014), but no correlation was found with hemodynamics
      or 6-minute-walk distance. The 5-year survival rate for the entire group was 68%.
      Kaplan-Meier analysis and multivariate Cox proportional hazard models correcting
      for demographic and clinical covariates revealed that patients with HbA1c < 5.7%
      had a significantly better 5-year survival compared with those having higher
      initial values (85.1% vs. 55.9%; log rank p = 0.002). HbA1c was a predictor of
      all-cause mortality with a hazard ratio of 2.23 (95% CI 1.06 to 4.70; p = 0.034)
      per 1-unit increase of HbA1c. CONCLUSIONS: In patients with pulmonary arterial
      hypertension, the HbA1c level at time of diagnosis is an independent predictor of
      long-term prognosis.

PMID- 22975102
TI  - Delayed sternal closure does not increase late infection risk in patients
      undergoing left ventricular assist device implantation.
AB  - BACKGROUND: Delayed sternal closure (DSC) is employed after conventional cardiac
      surgery without a significantly increased risk of late mediastinitis or sternal
      wound infection. There are no data specifically examining its late effects on
      patients undergoing implantation with a ventricular assist device (VAD). METHODS:
      Between October 1996 and October 2010, 364 patients underwent primary VAD implant
      and DSC was utilized in 184 (51%) patients for coagulopathy (n = 155; 84%),
      hemodynamic instability (n = 103; 56%), isolated right ventricular dysfunction (n
      = 15; 8%) or unspecified reasons (n = 17; 9%). RESULTS: Median duration of DSC
      was 1 day (range 1 to 7 days). Patients with DSC were older (54.5 vs. 50.3 years,
      p = 0.002), had a higher incidence of previous sternotomy (42% vs. 28%, p =
      0.005), pre-operative intra-aortic balloon pump (50% vs. 30%, p < 0.001), pre
      operative temporary extracorporeal mechanical circulatory support (23% vs 10%, p
      < 0.001), lower platelet counts (171,000 vs. 209,000, p < 0.001) and lower
      hematocrit levels (32% vs. 36%, p < 0.001). Operative (11% vs. 9%, p = 0.65) or
      late (2 years; 66 +/- 7% vs 66 +/- 7%, p = 0.720) mortality; composite incidence
      of mediastinitis, percutaneous drive-line infection, pocket infection and VAD
      related endocarditis (15% vs. 16%, p = 0.79); re-exploration for bleeding (18%
      vs. 18%, p = 0.99); urgent transplantation for infection (4% vs. 3%, p = 0.99);
      or need for device exchange (9% vs. 10%, p = 0.16) was not increased after DSC
      when compared with immediate sternal closure. DSC increased ICU stay (10 vs. 5
      days, p = 0.001). CONCLUSIONS: DSC was performed most commonly for coagulopathy
      and/or hemodynamic instability, and patients were older with a greater severity
      of illness as shown by the higher incidence of right-sided circulatory failure
      and history of prior sternotomy. Although DSC was associated with longer ICU
      stay, DSC was not associated with a significantly increased risk of death or
      infection.

PMID- 22975103
TI  - Physiologic assessment of the ex vivo donor lung for transplantation.
AB  - BACKGROUND: The evaluation of donor lungs by normothermic ex vivo acellular
      perfusion has improved the safety of organ utilization. However, this strategy
      requires a critical re-evaluation of the parameters used to assess lungs during
      ex vivo perfusion compared with those traditionally used to evaluate the donor
      lung in vivo. Using a porcine model, we studied the physiology of acellular lung
      perfusion with the aim of improving the accuracy of clinical ex vivo evaluation.
      METHODS: Porcine lungs after 10 hours of brain death and 24 hours of cold
      ischemia and uninjured control lungs were perfused for 12 hours and then
      transplanted. PaO2, compliance, airway pressure and pulmonary vascular resistance
      were measured. Ventilation with 100% nitrogen and addition of red blood cells to
      the perfusate were used to clarify the physiologic disparities between in vivo
      blood perfusion and ex vivo acellular perfusion. RESULTS: During 12 hours of ex
      vivo perfusion, injured lungs developed edema with decreased compliance and
      increased airway pressure, but ex vivo PO2 remained stable. After
      transplantation, injured lungs demonstrated high vascular resistance and poor
      PaO2. A reduced effect of shunt on ex vivo lung perfusion PO2 was found to be
      attributable to the linearization of the relationship between oxygen content and
      PO2, which occurs with acellular perfusate. CONCLUSIONS: Ex vivo PO2 may not be
      the first indication of lung injury and, taken alone, may be misleading in
      assessing the ex vivo lung. Thus, evaluation of other physiologic parameters
      takes on greater importance.

PMID- 22975105
TI  - Regulation of lung transplantation in China.

PMID- 22975106
TI  - Partial nephrectomy is the standard of care for T1a kidney tumors.

PMID- 22975104
TI  - Regulation of cyclic adenosine monophosphate release by selective beta2
      adrenergic receptor stimulation in human terminal failing myocardium before and
      after ventricular assist device support.
AB  - BACKGROUND: Response to catecholamines is blunted in terminal heart failure due
      to beta-receptor downregulation and uncoupling from adenylyl cyclase (AC).
      Improved myocardial responsiveness to catecholamines after ventricular assist
      device (VAD) support is associated with upregulation of beta1-adrenergic
      receptors (beta1-ARs). Little is known about the regulation of AC and beta2-AR
      coupling after VAD; moreover beta2-AR stimulation during VAD was claimed to
      induce myocardial recovery. METHODS: We analyzed in VAD-supported human
      myocardium the regulation of AC activity upon beta1-AR and selective beta2-AR
      stimulation in 8 non-failing hearts (NF) and 17 paired samples of VAD patients.
      AC messenger RNA was measured by TaqMan. AC was stimulated via beta2-AR using
      clenbuterol (beta2-AR agonist) and bisoprolol (beta1-AR blocker). Organ bath
      experiments were done with trabeculae from both ventricles. Samples were
      stratified according to chronic or acute heart failure history. RESULTS:
      Isoprenaline-induced AC activity was downregulated (p < 0.001) pre-VAD and
      increased significantly (p < 0.05) after unloading (mean +/- standard deviation
      pmole/mg/min) in NF (47.9 +/- 14.9), pre-VAD (24.35 +/- 13.3), and post-VAD
      (50.04 +/- 50.25). Forskolin stimulation revealed significant (p < 0.05)
      upregulation of AC activity during VAD, especially in acutely failing hearts (NF,
      192.1 +/- 68.7; pre-VAD, 191.1 +/- 60.4; post-VAD, 281.5 +/- 133). However,
      forskolin stimulation relative to isoprenaline-induced inotropy remained reduced
      before and after VAD compared with NF. The selective stimulation of beta2-AR did
      not reveal influence of VAD support on beta2-AR-AC coupling. Stimulation of
      ventricular trabeculae by > 100 MUmole/liter clenbuterol revealed negative
      inotropic responses. CONCLUSIONS: VAD does not influence beta2-AR coupling to AC
      stimulation. Elevated response to catecholamines after VAD support is influenced
      by beta1-AR upregulation and modulation of AC activity. Restoration of beta
      adrenergic responsiveness was restricted to acutely failing hearts.

PMID- 22975108
TI  - Transplantation techniques for the resection of renal cell carcinoma with tumor
      thrombus: a technical description and review.
AB  - Renal cell carcinoma with tumor thrombus of the inferior vena cava presents a
      special surgical challenge. The use of surgical techniques derived from the field
      of transplantation surgery have previously been shown to enable optimal control
      of inferior vena cava, allowing for the extirpation of most tumors via a
      transabdominal approach without the need for venovenous or cardiopulmonary
      bypass. In this report, we provide a stepwise description of the transplantation
      techniques employed at the University of Miami/Jackson Memorial Hospital for the
      resection of renal cell carcinoma with intracaval tumor. In addition, we review
      the results of centers that have utilized these surgical maneuvers. 

PMID- 22975107
TI  - Cognitive problems in patients on androgen deprivation therapy: a qualitative
      pilot study.
AB  - OBJECTIVES: Androgen deprivation therapy (ADT; also known as hormone therapy) is
      a well-established treatment for prostate cancer patients with rising prostate
      specific antigen levels after localized treatment, and for those with metastatic
      disease. The neurological impact of ADT has been likened to that of aging and is
      therefore theorized to impair cognitive functioning in prostate cancer patients.
      We briefly summarize the research that has examined cognitive functioning of ADT
      patients primarily through neuropsychological assessment. A qualitative pilot
      study is presented with the aim of describing ADT patients' experiences of
      cognitive changes since starting ADT. MATERIALS AND METHODS: Semistructured
      telephone interviews were undertaken with 11 community-dwelling prostate cancer
      patients undergoing ADT following definitive localized treatment. Participants
      were recruited via online prostate cancer support forums. Content analyses were
      conducted to establish relevant themes, which in this case were the cognitive
      domains of impairment. RESULTS: Eight of the 11 participants reported impairments
      in the domains of concentration, information processing, verbal fluency, visual
      information processing/visuospatial function, memory, and executive dysfunction.
      Neurobehavioral problems, including neurofatigue and apathy were also reported.
      CONCLUSIONS: The interviews illustrate the potential negative effects of ADT on
      cognitive and neurobehavioral functions, and their impact on patients' work and
      in their daily lives. We describe how the field of cognitive rehabilitation
      offers promising tools to assist ADT patients with cognitive problems.

PMID- 22975109
TI  - Increased percentage of CD8+CD28- T cells correlates with clinical activity in
      primary Sjogren's syndrome.
AB  - The role of CD28- T cell subpopulations in primary Sjogren's syndrome (pSS) has
      become controversial. Changes in the number of CD28- T cells have been
      demonstrated in autoimmune diseases in co-existence with Sjogren's syndrome. The
      study aimed to indicate differences in the number of CD4+CD28- and CD8+CD28- T
      cells in patients with sicca syndrome and suspected pSS. Thirty patients with
      sicca syndrome at baseline were studied and followed up for 5 months. After final
      diagnosis, comparison was made of the previously recorded lymphocyte
      subpopulations in patients with pSS and those in other defined subgroups. Notably
      high percentages of CD8+CD28- T cells were indicated in pSS patients, which
      correlated with the severity of the sicca symptoms and cutaneous and muscular
      systemic disease activity. Changes in CD8+CD28- T cell percentages may thus
      assist in the early differential diagnosis of pSS patients from those with
      similar clinical symptoms.

PMID- 22975111
TI  - Severity of obstructive airway disease and risk of fracture.

PMID- 22975110
TI  - Low osteocalcin/collagen type I bone gene expression ratio is associated with hip
      fragility fractures.
AB  - INTRODUCTION: Osteocalcin (OC) is the most abundant non-collagenous bone protein
      and is determinant for bone mineralization. We aimed to compare OC bone
      expression and serum factors related to its carboxylation in hip fragility
      fracture and osteoarthritis patients. We also aimed to identify which of these
      factors were associated with worse mechanical behavior and with the hip fracture
      event. METHODS: In this case-control study, fragility fracture patients submitted
      to hip replacement surgery were evaluated and compared to a group of
      osteoarthritis patients submitted to the same procedure. Fasting blood samples
      were collected to assess apolipoproteinE (apoE) levels, total OC and
      undercarboxylated osteocalcin (ucOC), vitamin K, LDL cholesterol, triglycerides
      and bone turnover markers. The frequency of the apoepsilon4 isoform was
      determined. Femoral epiphyses were collected and trabecular bone cylinders
      drilled in order to perform compression mechanical tests. Gene expression of bone
      matrix components was assessed by quantitative RT-PCR analysis. RESULTS: 64
      patients, 25 submitted to hip replacement surgery due to fragility fracture and
      39 due to osteoarthritis, were evaluated. Bone OC/collagen expression (OC/COL1A1)
      ratio was significantly lower in hip fracture compared to osteoarthritis patients
      (p<0.017) adjusted for age, gender and body mass index. Moreover, OC/COL1A1
      expression ratio was associated with the hip fracture event (OR ~0; p=0.003)
      independently of the group assigned, or the clinical characteristics. Apoepsilon4
      isoform was more frequent in the hip fracture group (p=0.029). ucOC levels were
      higher in the fracture group although not significantly (p=0.058). No differences
      were found regarding total OC (p=0.602), apoE (p=0.467) and Vitamin K (p=0.371).
      In hip fracture patients, multivariate analysis, adjusted for clinical
      characteristics, serum factors related to OC metabolism and gene expression of
      bone matrix proteins showed that low OC/COL1A1 expression ratio was significantly
      associated with worse trabecular strength (beta=0.607; p=0.013) and stiffness
      (beta=0.693; p=0.003). No association was found between ucOC and bone mechanics.
      Moreover, in osteoarthritis patients, the multivariate analysis revealed that
      serum total OC was negatively associated with strength (beta=-0.411; p=0.030) and
      stiffness (beta=-0.487; p=0.009). CONCLUSION: We demonstrated that low bone
      OC/COL1A1 expression ratio was an independent predictor of worse trabecular
      mechanical behavior and of the hip fracture event. These findings suggest that in
      hip fracture patients the imbalance of bone OC/COL1A1 expression ratio reflects
      disturbances in osteoblast activity leading to bone fragility.

PMID- 22975112
TI  - Recommendations for reducing the risk of viral transmission during fertility
      treatment with the use of autologous gametes: a committee opinion.
AB  - This document provides strategies, based on scientific principles and clinical
      experience, to reduce the risk of viral transmission in couples seeking treatment
      for infertility using their own gametes. This document replaces the ASRM Practice
      Committee document, "Guidelines for reducing the risk of viral transmission
      during fertility treatment," last published in Fertil Steril 2008;90(5
      Suppl):S156-62.

PMID- 22975114
TI  - Surgical excision of endometriomas and ovarian reserve: a systematic review on
      serum antimullerian hormone level modifications.
AB  - OBJECTIVE: To evaluate serum antimullerian hormone (AMH) level modification after
      surgical excision of ovarian endometriomas. DESIGN: Systematic review. MEDLINE
      search from January 1990 to April 2012 using the combination of medical terms
      endometriosis, endometrioma, endometriotic cyst, and AMH or antimullerian
      hormone, MIF or mullerian inhibiting factor. Reference lists of selected studies
      were checked for additional potential contributions. SETTING: Not applicable.
      PATIENT(S): Women with ovarian endometriomas requiring surgery. INTERVENTION(S):
      Serum AMH level assessment. MAIN OUTCOME MEASURE(S): Serum AMH level
      modifications. RESULT(S): Eleven articles satisfied our selection criteria. Data
      pooling were deemed inopportune owing to the heterogeneity of the study designs
      and of the reported parameters. Nine of 11 studies documented a statistically
      significant reduction of serum AMH level after surgery. The two studies failing
      to document this decrease were published by the same study group and partly
      overlapped. The magnitude of the decline was more evident in women operated on
      for bilateral endometriomas. CONCLUSION(S): Evidence deriving from the evaluation
      of serum AMH level modifications after surgical excision of endometriomas
      supports a surgery-related damage to ovarian reserve.

PMID- 22975113
TI  - Embryo incubation and selection in a time-lapse monitoring system improves
      pregnancy outcome compared with a standard incubator: a retrospective cohort
      study.
AB  - OBJECTIVE: To quantify the effect on reproductive outcome of culturing and
      selecting embryos using a novel time-lapse monitoring system (TMS). DESIGN:
      Retrospective observational cohort study. SETTING: University-affiliated private
      center. PATIENT(S): Donation and autologous intracytoplasmic sperm injection
      (ICSI) cycles from ten IVF clinics using similar procedures, cultured in TMS (n =
      1,390) or in a standard incubator (SI; n = 5,915). INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Clinical pregnancy rate confirmed by ultrasound in week 7.
      RESULT(S): A logistic regression analysis, which included all significant
      confounding factors, was used to evaluate the effect of culturing and selecting
      embryos with the use of TMS. Comparing clinical pregnancy rates per oocyte
      retrieval with TMS and SI treatments gave a crude effect of odds ratio [OR] 1.190
      (95% confidence interval [CI] 1.058-1.337). Oocyte source, maternal age, day of
      transfer, and number of retrieved oocytes were identified as significant
      confounding factors. After accounting for confounding factors, the effect of TMS
      culture was OR 1.201 (95% CI 1.059-1.363). Limiting analysis to treatments with
      embryo transfer and including number of transferred embryos as a confounding
      factor likewise gave a significant effect of TMS with OR 1.157 (95% CI 1.018
      1.315). CONCLUSION(S): Analysis of retrospective data indicated that culturing
      and selecting embryos by TMS significantly improved the relative probability of
      clinical pregnancy (+20.1% per oocyte retrieval, +15.7% per embryo transfer). The
      elevated clinical pregnancy rate was attributed to a combination of stable
      culture conditions and the use of morphokinetic parameters for embryo selection.

PMID- 22975115
TI  - Horse serum reduces expression of membrane-bound and soluble isoforms of the
      preadipocyte marker Delta-like 1 homolog (Dlk1), but is inefficient for
      adipogenic differentiation of mouse preadipocytes.
AB  - Downregulation of the preadipocyte marker Delta-like 1 homologue (Dlk1), an
      inhibitor of adipogenesis, has been suggested to be a prerequisite for adipogenic
      differentiation to occur, and low Dlk1 levels are often used to verify
      adipogenesis. Mouse preadipocytic cell lines such as 3T3-L1, as well as primary
      derived preadipocytes, are important models to study adipogenic differentiation
      and obesity. However, in vitro adipogenic differentiation of primary derived
      preadipocytes remains incomplete, and identification of factors that will improve
      the adipogenic differentiation process is thus of high value. In this study we
      show that horse serum fails to improve adipogenic differentiation of mouse
      preadipocytes (both 3T3-L1 cells and primary derived mouse preadipocytes) as
      otherwise reported for bone marrow derived adipogenic precursors. Unexpectedly,
      while Dlk1 levels were indeed decreased using horse serum, this did not correlate
      with a high degree of adipogenic differentiation. In conclusion, our novel
      results thus reveal that horse serum clearly is insufficient for adipogenic
      differentiation of mouse preadipocytes and that low levels of Dlk1 alone are a
      poor marker of mouse in vitro adipogenesis. We would also like to emphasize that
      it is very important for the field of cellular differentiation that researchers
      thoroughly investigate the effect of individual reagents in their protocols. Such
      data will increase understanding of the limitations and possibilities of
      individual systems.

PMID- 22975116
TI  - Pigment epithelial-derived factor expression in endometriotic lesions in a rat
      model of endometriosis.
AB  - Angiogenesis is a prerequisite for endometriotic lesion formation and
      development. Pigment epithelium-derived factor (PEDF) is a potential inhibitor of
      angiogenesis. The objective of this study was to detect PEDF immunolocalization
      in endometriotic lesions and the correlation with vascular endothelial growth
      factor (VEGF) and microvascular density (MVD) in a rat model of endometriosis. A
      subcutaneous endometriosis rat model was established by using auto
      transplantation. Expression of PEDF, VEGF and MVD labeled by von Willebrand
      factor (v-WF) in endometriotic lesions and endometrial tissues was evaluated
      using immunohistochemical staining. We detected lower PEDF immunostaining and
      higher VEGF and MVD immunostaining in active lesions in a rat model of
      endometriosis than that in endometriosis endometrium or control endometrium
      (P<0.05), but no differences between endometriosis and control endometrium were
      found (P>0.05). In lesions, PEDF expression was negatively correlated with VEGF
      expression, MVD or sizes of cysts (P<0.01). On the contrary, both VEGF expression
      and MVD were positively correlated with lesion sizes (P<0.05). In addition, VEGF
      expression was positively correlated with MVD (P<0.01). Our results suggest that
      PEDF might be involved in the pathogenesis of endometriosis and may lead to novel
      treatment for this disease.

PMID- 22975117
TI  - Statin utilization according to indication and age: a Danish cohort study on
      changing prescribing and purchasing behaviour.
AB  - OBJECTIVE: Introduced to reduce mortality after myocardial infarction (MI),
      statins are now recommended for a range of other conditions, including
      asymptomatic individuals without cardiovascular disease or diabetes. The aim was
      to describe trends in Danish statin utilization according to indication and age
      during 1996-2009, and to analyse changing prescribing and purchasing behaviour
      during time intervals (driver periods) a priori defined by potential influential
      factors. METHODS: A nationwide cohort (N=4,998,580) was followed in Danish
      individual-level registries. Based on a hierarchy of register markers of
      indications for statin prescribing, we analysed incidence and prevalence of use
      by age and indication (age >= 40). Applying Poisson regression, we calculated
      Incidence Rate Ratios (IRR) of statin treatment for the last year of each driver
      period, applying the first year as reference. RESULTS: Treatment prevalence
      increased from 7/1000 to 187/1000, representing a shift towards lower-level
      indications and increased relatively more in individuals aged 75+. While
      treatment prevalence in MI-patients reached 780/1000, asymptomatic individuals
      represented 50% of incident statin-users in 2009. A marked increase in incidence
      of statin use occurred during 1999-2003 (IRR=3.05) across all indications,
      followed by a more moderate rise during 2003-2006 (IRR=1.29) and 2006-2008
      (IRR=1.15) - most marked increases in asymptomatic individuals. A sudden decrease
      was observed in 2009 (IRR=0.82) for all indications and ages. CONCLUSION: While
      patent expiry and lower prices most likely boosted the general increase in statin
      utilization, the gradually altered indication and age pattern seems to be driven
      by guidelines, influencing both reimbursement rules and general healthcare
      policies. A media debate on statin side effects may have modified the general
      attitudes.

PMID- 22975118
TI  - Stakeholder perceptions of a comprehensive school food policy in Western
      Australia.
AB  - OBJECTIVES: This study investigated stakeholder perceptions of the Healthy Food
      and Drink Policy that was recently implemented in Western Australian public
      schools. METHODS: A two-phase approach involving more than 1800 study
      participants assessed stakeholders' perceptions of the effects of the policy.
      Participating stakeholders included parents, principals, teachers, canteen
      managers, and Parents & Citizens Committee presidents. RESULTS: Despite numerous
      complaints being lodged when the policy was first introduced, the results suggest
      strong support across all stakeholder groups. A substantial majority of all
      stakeholder groups agreed that the policy has improved the healthiness of foods
      provided in schools and that the policy constitutes an important opportunity to
      educate children about healthy eating. CONCLUSIONS: The study outcomes indicate
      that policy makers should rely on representative data to assess stakeholder
      reactions to and support for new school food policies rather than giving undue
      credence to 'squeaky wheels'.

PMID- 22975119
TI  - The ICF: International Classification of Functioning, Disability and Health (ICF)
      -a Swiss army knife? Accessibility and disability in a Scandinavian disability
      magazine (SDM)--a quantitative content analysis.
AB  - BACKGROUND: The study describes the extent to which the concept of accessibility
      and accessibility issues has been reported in a national Scandinavian disability
      magazine. In this study particular attention is paid to how the compatibility
      between the various domains of the international classification - International
      Classification of Functioning, Disability and Health (ICF) - has been covered in
      the magazine over a decade. Furthermore, other types of descriptions that the
      magazine has made of accessibility for people with physical disabilities are
      considered. METHODS: The study is based on a quantitative content analysis of a
      total of 326 articles from the Swedish disability magazine (SDM); 450 text pages
      published during the years 2000-2009. The magazine's coverage has been
      comprehensive. RESULTS AND CONCLUSIONS: More than half of the studied texts were
      news items about various accessibility issues. Every third article can be
      characterised as a news article or feature article. The most frequently reported
      of the ICF domains consist of two perspectives: environmental accessibility and
      civil rights. Public opinion articles in the form of letters to editors and
      editorials focused on accessibility have a low frequency. Likewise, research
      reports are few. The study has included a review of illustrations and
      photographs. The illustrations are generally of high quality, reinforcing the
      disability message of the article.

PMID- 22975120
TI  - Characterization and solvent engineering of wheat beta-amylase for enhancing its
      activity and stability.
AB  - The kinetic and thermodynamic parameters of wheat beta-amylase (WBA) were
      characterized and various additives were evaluated for enhancing its activity and
      thermostability. WBA activity was examined by neocuproine method using soluble
      starch as substrate. The Michaelis constant (K(m)) and molecular activity
      (k(cat)) were determined to be 1.0+/-0.1% (w/v) and 94+/-3s(-1), respectively, at
      pH 5.4 and at 25 degrees C. The optimum reaction temperature (T(opt)) for WBA
      activity was 55 degrees C and the temperature (T(50)) at which it loses half of
      the activity after 30-min incubation was 50+/-1 degrees C. Modifications of the
      solvent with 182mM glycine and 0.18% (w/v) gelatin have increased the T(50) by 5
      degrees C. Glycerol, ethylene glycol, dimethylformamide (DMF) and dimethyl
      sulfoxide have also slightly enhanced the thermostability plausibly through
      weakening the water structure and decreasing the water shell around the WBA
      protein. Ethanol and DMF activated WBA by up to 24% at 25 degrees C probably by
      inducing favorable conformation for the active site or changing the substrate
      structure by weakening the hydrogen bonding. Its half-life in the inactivation at
      55 degrees C was improved from 23 to 48min by 182mM glycine. The thermodynamic
      parameters indicate that WBA is thermo-labile and sufficient stabilization was
      achieved through solvent modification with additives and that the heat
      inactivation of WBA is entropic-driven. It is suggested that WBA could be applied
      more widely in starch-saccharification industries with employing suitable
      additives.

PMID- 22975121
TI  - Activation of polymeric materials towards enzymatic postgrafting and cross
      linking.
AB  - A methodology to activate inert polymeric materials to enzymatic
      functionalisation is described herein. Plasma irradiation can be used to graft
      compounds containing a moiety that is reactive towards an enzyme of interest.
      Subsequently, such enzyme can be used to either postgraft functional compounds or
      cross-link the polymeric materials. Argon plasma was utilised to graft 2
      aminoethyl methacrylate onto cotton and wool fibres, introducing surface
      alkylamine groups to impart reactivity towards transglutaminase and tyrosinase.
      The efficiency of plasma grafting was verified by ATR-FTIR. Enzyme postgrafting
      of fluorescent peptides coupled with confocal microscopy was used to demonstrate
      transglutaminase activity towards cotton, a material typically inert to this
      enzyme. The grafting of alkylamines onto wool resulted in additional cross
      linking by both enzymes, leading to significantly increased yarn breaking load
      and elongation at break. This technology permits the activation of inert
      materials towards enzymatic postgrafting, with applications in fields as diverse
      as textiles and biomaterials.

PMID- 22975122
TI  - Putrescine biosensor based on putrescine oxidase from Kocuria rosea.
AB  - The novel putrescine oxidase based amperometric biosensor selectively measures
      putrescine, which can be considered as an indicator of microbial spoilage.
      Putrescine oxidase (PUOX, EC 1.4.3.10) was isolated from Kocuria rosea
      (Micrococcus rubens) by an improved and simplified purification process. Cells
      were grown on brain heart infusion medium supplemented with putrescine. Cell-free
      extract was prepared in Tris buffer (pH 8.0) by Bead-beater. A newly elaborated
      step based on three-phase partitioning (TPP) was applied in the purification
      protocol of PUOX. The purified enzyme was immobilized on the surface of a
      spectroscopic graphite electrode in redox hydrogel with horseradish peroxidase,
      Os mediator and poly(ethylene glycol) (400) diglycidyl ether (PEGDGE) as
      crosslinking agent. This modified working electrode was used in wall-jet type
      amperometric cell together with the Ag/AgCl (0.1M KCl) reference electrode and a
      platinum wire as auxiliary electrode in flow injection analysis system (FIA).
      Hydrogel composition, pH and potential dependence were studied. Optimal working
      conditions were 0.45 mLmin(-1) flow rate of phosphate buffer (66 mM, pH 8.0) and
      +50 mV polarizing potential vs. Ag/AgCl. The linear measuring range of the method
      was 0.01-0.25 mM putrescine, while the detection limit was 5 MUM. Beer samples
      were investigated by the putrescine biosensor and the results were compared by
      those of HPLC reference method.

PMID- 22975123
TI  - Efficient production of l-lactic acid from hydrolysate of Jerusalem artichoke
      with immobilized cells of Lactococcus lactis in fibrous bed bioreactors.
AB  - Hydrolysate of Jerusalem artichoke was applied for the production of l-lactic
      acid by immobilized Lactococcus lactis cells in a fibrous bed bioreactor system.
      Preliminary experiments had indicated that the high quality hydrolysate, which
      was derived from the 40 min acid treatment at 95  degrees C and pH 1.8, was
      sufficient to support the cell growth and synthesis of l-lactic acid. With the
      addition of 5 g/l yeast extract, the fermentative performance of free cell system
      was evidently improved. After the basal settlement of hydrolysate based
      fermentation, the batch mode and the fed-batch mode fermentation were carried out
      in the free cell system and the fibrous bed bioreactor system, respectively. In
      all cases the immobilized cells presented the superior ability to produce l
      lactic acid. The comparison of batch mode and fed-batch mode also indicated that
      the growth-limiting feeding strategy could reduce the lag phase of fermentation
      process and enhance the production of l-lactic acid. The achieved maximum
      concentration of l-lactic acid was 142 g/l in the fed-batch mode. Subsequent
      repeated-batch fermentation of the fibrous bed bioreactor system had further
      exhibited the persistence and stability of this system for the high production of
      l-lactic acid in a long term. Our work suggested the great potential of the
      fibrous bed bioreactor system and hydrolysate of J. artichoke in the economical
      production of l-lactic acid at industrial scale.

PMID- 22975124
TI  - Power generation from cellulose using mixed and pure cultures of cellulose
      degrading bacteria in a microbial fuel cell.
AB  - Microbial fuel cells (MFCs) have been used to generate electricity from various
      organic compounds such as acetate, glucose, and lactate. We demonstrate here that
      electricity can be produced in an MFC using cellulose as the electron donor
      source. Tests were conducted using two-chambered MFCs, the anode medium was
      inoculated with mixed or pure culture of cellulose-degrading bacteria
      Nocardiopsis sp. KNU (S strain) or Streptomyces enissocaesilis KNU (K strain),
      and the catholyte in the cathode compartment was 50mM ferricyanide as catholyte.
      The power density for the mixed culture was 0.188 mW (188 mW/m(2)) at a current
      of 0.5mA when 1g/L cellulose was used. However, the power density decreased as
      the cellulose concentration in the anode compartment decreased. The columbic
      efficiencies (CEs) ranged from 41.5 to 33.4%, corresponding to an initial
      cellulose concentration of 0.1-1.0 g/L. For the pure culture, cellobioase enzyme
      was added to increase the conversion of cellulose to simple sugars, since
      electricity production is very low. The power densities for S and K strain pure
      cultures with cellobioase were 162 mW/m(2) and 145 mW/m(2), respectively. Cyclic
      voltammetry (CV) experiments showed the presence of peaks at 380, 500, and 720 mV
      vs. Ag/AgCl for the mixed bacterial culture, indicating its electrochemical
      activity without an external mediator. Furthermore, this MFC system employs a
      unique microbial ecology in which both the electron donor (cellulose) and the
      electron acceptor (carbon paper) are insoluble.

PMID- 22975125
TI  - Characterization of the major dehydrogenase related to d-lactic acid synthesis in
      Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293.
AB  - Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 is a lactic acid
      bacterium that converts pyruvate mainly to d-(-)-lactic acid by using d-(-)
      lactate dehydrogenase (ldhD). The aim of this study was to identify the gene
      responsible for d-lactic acid formation in this organism and to characterize the
      enzyme to facilitate the production of optically pure d-lactic acid. A genomic
      analysis of L. mesenteroides ATCC 8293 revealed that 7 genes encode lactate
      related dehydrogenase. According to transcriptomic, proteomic, and phylogenetic
      analyses, LEUM_1756 was the major gene responsible for the production of d-lactic
      acid. The LEUM_1756 gene, of 996bp and encoding 332 amino acids (36.5kDa), was
      cloned and overexpressed in Escherichia coli BL21(DE3) Star from an inducible pET
      21a(+) vector. The enzyme was purified by Ni-NTA column chromatography and showed
      a specific activity of 4450U/mg, significantly higher than those of other
      previously reported ldhDs. The gel permeation chromatography analysis showed that
      the purified enzyme exists as tetramers in solution and this was the first report
      among lactic acid bacteria. The pH and temperature optima were pH 8.0 and 30
      degrees C, respectively, for the pyruvate reduction reaction, and pH 11.0 and 20
      degrees C, respectively, for the lactate oxidation reaction. The K(m) kinetic
      parameters for pyruvate and lactate were 0.58mM and 260mM, respectively. In
      addition, the k(cat) values for pyruvate and lactate were 2900s(-1) and 2280s(
      1), respectively. The enzyme was not inhibited by Ca(2+), Co(2+), Cu(2+), Mg(2+),
      Mn(2+), Na(+), or urea, but was inhibited by 1mM Zn(2+) and 1mM SDS.

PMID- 22975126
TI  - A simple and fast method for the determination of endo- and exo-cellulase
      activity in cellulase preparations using filter paper.
AB  - This study describes a procedure for the selective determination of endo- (EG)
      and exo- (ExG) cellulase activities using filter paper as the sole substrate. The
      procedure is based on the enzymes mode of action whereby EG activity
      predominantly forms insoluble reducing sugars and ExG activity soluble reducing
      sugars. The procedure was developed using filter paper as substrate for
      hydrolysis with three cellulase preparations of Hypocrea jecorina containing
      either endoglucanase (EG), predominantly exoglucanase (ExG) or both endo- and
      exoglucanase activities. Hydrolysis experiments, which were followed assessing
      the formation of total, soluble and insoluble reducing sugars (RS), showed that
      up to 30 min of hydrolysis predominantly insoluble reducing sugars were formed,
      while after this initial hydrolysis stage soluble reducing sugar formation
      increased significantly, making it thus possible to measure separately EG and ExG
      activity. FPA activities obtained from the reaction products at different
      reaction times suggest that EG-activity (FPA(insol)) should be measured between
      10 and 20 min of hydrolysis. The proposed procedure allows to evaluate the EG and
      ExG activity contribution to total cellulase activity and to calculate the
      endo/exo activity ratio of any cellulase preparation.

PMID- 22975127
TI  - Regulation of NAD(H) pool and NADH/NAD(+) ratio by overexpression of nicotinic
      acid phosphoribosyltransferase for succinic acid production in Escherichia coli
      NZN111.
AB  - Succinic acid is not the dominant fermentation product from glucose in wild-type
      Escherichia coli W1485. To reduce byproduct formation and increase succinic acid
      accumulation, pyruvate formate-lyase and lactate dehydrogenase, encoded by pflB
      and ldhA genes, were inactivated. However, E. coli NZN111, the ldhA and pflB
      deletion strain, could not utilize glucose anaerobically due to the block of
      NAD(+) regeneration. To restore glucose utilization, overexpression of nicotinic
      acid phosphoribosyltransferase, a rate limiting enzyme of NAD(H) synthesis
      encoded by the pncB gene, resulted in a significant increase in cell mass and
      succinic acid production. Furthermore, the results indicated a significant
      increase in NAD(H) pool size, and decrease in the NADH/NAD(+) ratio from 0.64 to
      0.13, in particular, the concentration of NAD(+) increased 6.2-fold during
      anaerobic fermentation. In other words, the supply of enough NAD(+) for NADH
      oxidation by regulation of NAD(H) salvage synthesis mechanism could improve the
      cell growth and glucose utilization anaerobically. In addition, the low
      NADH/NAD(+) ratio also change the metabolite distribution during the dual-phase
      fermentation. As a result, there was a significant increase in succinic acid
      production, and it is provided further evidence that regulation of NAD(H) pool
      and NADH/NAD(+) ratio was very important for succinic acid production.

PMID- 22975128
TI  - Enhanced accumulation of starch and total carbohydrates in alginate-immobilized
      Chlorella spp. induced by Azospirillum brasilense: I. Autotrophic conditions.
AB  - The effect of the microalgae-growth promoting bacterium Azospirillum brasilense
      on accumulation of total carbohydrates and starch in two species of Chlorella
      (Chlorella vulgaris and Chlorella sorokiniana), when the bacterium and each
      microalga were jointly immobilized in alginate beads was studied under
      autotrophic conditions for 144 h in synthetic medium. The interaction of the
      bacterium with the microalgae enhanced accumulation of total carbohydrate and
      starch. Cells of Chlorella accumulated the highest amounts of carbohydrate after
      incubation for 24h. Yet, this did not coincide with the highest affinity and
      volumetric productivity measured in these cultures. However, after incubation for
      72 h, mainly in jointly immobilized treatments of both microalgae species, the
      cultures reached their highest total carbohydrate content (mainly as starch) and
      also the highest affinity and volumetric productivity. These results demonstrate
      the potential of A. brasilense to affect carbohydrates and starch accumulation in
      Chlorella spp. when both microorganisms are co-cultured, which can be an
      important tool for applications of microalgae.

PMID- 22975129
TI  - Enhanced accumulation of starch and total carbohydrates in alginate-immobilized
      Chlorella spp. induced by Azospirillum brasilense: II. Heterotrophic conditions.
AB  - The effect of the bacterium Azospirillum brasilense jointly immobilized with
      Chlorella vulgaris or C. sorokiniana in alginate beads on total carbohydrates and
      starch was studied under dark and heterotrophic conditions for 144 h in synthetic
      growth medium supplemented with either d-glucose or Na-acetate as carbon sources.
      In all treatments, enhanced total carbohydrates and starch content per culture
      and per cell was obtained after 24h; only jointly immobilized C. vulgaris growing
      on d-glucose significantly increased total carbohydrates and starch content after
      96 h. Enhanced accumulation of carbohydrate and starch under jointly immobilized
      conditions was variable with time of sampling and substrate used. Similar results
      occurred when the microalgae was immobilized alone. In both microalgae growing on
      either carbon sources, the bacterium promoted accumulation of carbohydrates and
      starch; when the microalgae were immobilized alone, they used the carbon sources
      for cell multiplication. In jointly immobilized conditions with Chlorella spp.,
      affinity to carbon source and volumetric productivity and yield were higher than
      when Chlorella spp. were immobilized alone; however, the growth rate was higher
      in microalgae immobilized alone. This study demonstrates that under heterotrophic
      conditions, A. brasilense promotes the accumulation of carbohydrates in two
      strains Chlorella spp. under certain time-substrate combinations, producing
      mainly starch. As such, this bacterium is a biological factor that can change the
      composition of compounds in microalgae in dark, heterotrophic conditions.

PMID- 22975130
TI  - Prevention of traumatic brain injury-induced neuronal death by inhibition of
      NADPH oxidase activation.
AB  - The present study aimed to evaluate the therapeutic potential of apocynin, an
      NADPH oxidase assembly inhibitor, on traumatic brain injury. Rat traumatic brain
      injury (TBI) was performed using a weight drop model. Apocynin (100mg/kg) was
      injected into the intraperitoneal space 15 min before TBI. Reactive oxygen
      species (ROS) in the hippocampal CA3 pyramidal neurons were detected by
      dihydroethidium (dHEt) at 3h after TBI. Oxidative injury was detected by 4
      hydroxy-2-nonenal (4HNE) at 6h after TBI. Blood-brain barrier disruption was
      detected by IgG extravasation and neuronal death was evaluated with Fluoro Jade-B
      staining 24h after TBI. Microglia activation was detected by CD11b
      immunohistochemistry in the hippocampus at 1 week after TBI. ROS production was
      inhibited by apocynin administration in the hippocampal CA3 pyramidal neurons.
      This pre-treatment with apocynin decreased the blood-brain barrier disruption,
      the number of degenerating neurons in the hippocampal CA3 region and microglial
      activation after TBI. The present study indicates that apocynin pre-treatment
      prevents TBI-induced ROS production, thus decreasing BBB disruption, neuronal
      death and microglial activation. Therefore, the present study suggests that
      inhibition of NADPH oxidase by apocynin may have a high therapeutic potential to
      reduce traumatic brain injury-induced neuronal death.

PMID- 22975131
TI  - Transgenic medaka fish which mimic the endogenous expression of neuronal kinesin,
      KIF5A.
AB  - Intracellular transport is spatiotemporally controlled by microtubule-dependent
      motor proteins, including kinesins. In order to elucidate the mechanisms
      controlling kinesin expression, it is important to analyze their genomic
      regulatory regions. In this study, we cloned the neuronal tissue-specific kinesin
      in medaka fish and generated transgenic fish which mimic endogenous neuronal
      kinesin expression in order to elucidate the mechanisms which regulate kinesin
      expression. Searches for medaka neuronal orthologues by RT-PCR identified a
      candidate gene expressed only in neuronal tissues. Using BAC clones, we
      determined the cDNA sequence and the gene structure of the candidate neuronal
      kinesin. Evolutionary analysis indicated that the candidate gene encoded medaka
      KIF5Aa. The endogenous medaka orthologue was found to be expressed only in the
      nervous system, including the brain and spinal cord, while expression of KIF5Ab
      was not exclusive to neuronal tissues. Transgenic (Tg) medaka that expressed EGFP
      under the control of the 6.9 kbp 5' and 1.9kbp 3' flanking regions of the KIF5Aa
      gene showed characteristic expression throughout the nervous system, including
      the brain, spinal cord, olfactory pit, eye and cranial nerve. Immunohistological
      analysis showed that EGFP expression in Tg fish co-localized with expression of
      HuC/D, a neuronal marker. These results demonstrate that the 6.9 kbp 5' and 1.9
      kbp 3' flanking regions of medaka KIF5Aa have neuronal-specific promoter activity
      mimicking endogenous expression of medaka KIF5Ab. This transgenic fish strain
      will be useful for further functional analysis of the effects of these regulatory
      regions on gene expression.

PMID- 22975132
TI  - Expression of CD200 in alternative activation of microglia following an
      excitotoxic lesion in the mouse hippocampus.
AB  - CD200 is a glycoprotein that is expressed on the surfaces of neurons and other
      cells. It interacts with its receptor, CD200R, which is expressed on cells of the
      myeloid lineage, including microglia. The interaction of CD200 with its receptor
      plays a significant role in maintaining microglia in a quiescent state; thus, a
      decrease in CD200 expression in the brain is associated with evidence of
      microglial activation. However, their roles in pathological progression remain
      unclear. We examined the expression of CD200 in kainic acid (KA)-induced
      neurodegeneration of the mouse hippocampus. Our quantitative analysis revealed
      that CD200 was constitutively expressed in the normal brain and transiently
      upregulated by KA treatment. At the cellular level, CD200 was expressed in
      neurons in control, and was upregulated primarily in the microglia of KA-treated
      mouse hippocampi. We examined the contribution of CD200 to both the classical and
      alternative activation of microglia in vitro using an adult microglia culture,
      which was exposed to interleukin-4 (IL-4) with and without lipopolysaccharide
      (LPS). CD200 expression was increased after exposure to IL-4, but not to LPS.
      These in vivo experiments demonstrated that CD200 was transiently expressed in
      microglia in a process mediated by the inflammatory response. Based on CD200R
      expression in microglia, it suggests that microglia is maintained in an activated
      state with autocrine signaling by interactions between microglial CD200 and its
      CD200R. Moreover, we suggest that CD200 may be expressed in the alternative
      activation of microglia and play a beneficial role in neuroinflammation.

PMID- 22975133
TI  - Vasopressin-induced intracellular Ca2+ concentration responses in non-neuronal
      cells of the rat dorsal root ganglion.
AB  - Arginine-vasopressin (AVP) is a nonapeptide of hypothalamic origin that has been
      shown to exert many important cognitive and physiological functions in neurons
      and terminals of both the central and peripheral nervous system (CNS and PNS).
      Here we report for the first time that AVP induced an increase in intracellular
      Ca2+ concentration ([Ca2+](i)) in non-neuronal cells isolated from the rat dorsal
      root ganglion (DRG) and cultured in vitro. The ratiometric [Ca2+](i) measurements
      showed that AVP evoked [Ca2+](i) responses in the non-neuronal cells and these
      concentration-dependent (100 pM to 1 MUM) responses increased with days in vitro
      in culture, reaching a maximum amplitude after 4-5 day. Immunostaining by anti-S
      100 antibody revealed that more than 70% of S-100 positive cells were AVP
      responsive, indicating that glial cells responded to AVP and increased their
      [Ca2+](i). The responses were inhibited by depletion of the intracellular Ca2+
      stores or in the presence of inhibitors of phospholipase C, indicating a
      metabotropic response involving inositol trisphosphate, and were mediated by the
      V1 subclass of AVP receptors, as evidenced by the use of the specific blockers
      for V1 and OT receptors, (d(CH2)51,Tyr(Me)2,Arg8)-Vasopressin and
      (d(CH2)51,Tyr(Me)2,Thr4,Orn8,des-Gly-NH29)-Vasotocin, respectively. V(1a) but not
      V(1b) receptor mRNA was expressed sustainably through the culture period in
      cultured DRG cells. These results suggest that AVP modulates the activity of DRG
      glial cells via activation of V(1a) receptor.

PMID- 22975134
TI  - Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency
      associated hearing loss.
AB  - Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are
      responsible for ~50% of nonsyndromic hearing loss in children. Mouse models show
      that Cx26 deficiency induces cochlear development disorder, hair cell loss, and
      spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration
      have been considered as a primary causer responsible for Cx26 deficiency
      associated hearing loss. In this study, by coincidental examination of cochlear
      postnatal development with recording of auditory brainstem response (ABR) and
      hair cell function, we found that occurrence of hearing loss in Cx26 knockout
      (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was
      absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear
      cells including SG neurons had no significant degeneration throughout postnatal
      development. Severe cochlear hair cell loss and SG neuron degeneration were only
      visible in middle and basal turns, i.e., in middle and high frequency regions, in
      the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO
      mice functioned normally; outer hair cells retained electromotility. These data
      suggest that cell degeneration is not a primary causer of Cx26 deficiency
      associated hearing loss. Some mechanisms other than cell degeneration, such as
      cochlear development disorders, may play an essential role in this common
      hereditary deafness.

PMID- 22975136
TI  - Inflammation of temporomandibular joint increases neural activity in rat
      vestibular nucleus.
AB  - To determine whether the vestibular nuclei are affected by inflammation of
      temporomandibular joint (TMJ) region, we studied vestibular nucleus neural
      activity using two experimental groups: (1) normal saline 0.1cm(3) injection at
      right TMJ region, (2) 10% formalin 0.1cm(3) injection at right TMJ region. Neural
      activity after 24 hours was assessed by immunohistochemical staining with free
      floating section at the level of interaural -1.30 mm to -2.00 mm for c-Fos. In
      inflammation group, formalin injection produced a bilateral increase in c-Fos at
      vestibular nucleus with ipsilesional side higher activity. In control group,
      expression of c-Fos protein was also observed in the vestibular nucleus (VN),
      especially MVN. But stain intensity of Fos-positive neurons was much weaker and
      mean number of c-Fos positive cells was fewer than inflammation group. This
      result suggests that there is a close neural connection between TMJ and
      vestibular nucleus, especially in case of inflammation.

PMID- 22975135
TI  - RNF11 modulates microglia activation through NF-kappaB signalling cascade.
AB  - Microglia are resident macrophages in the central nervous system (CNS) that play
      a major role in neuroinflammation and pathogenesis of several neurodegenerative
      diseases. Upon activation, microglia releases a multitude of pro-inflammatory
      factors that initiate and sustain an inflammatory response by activating various
      signalling pathways, including the NF-kappaB pathway in a feed forward cycle. In
      microglial cells, activation of NF-kappaB signalling is normally transient, while
      sustained NF-kappaB activation is associated with persistent neuroinflammation.
      RING finger protein 11 (RNF11), in association with A20 ubiquitin-editing
      complex, is one of the key negative regulators of NF-kappaB signalling pathway in
      neurons. In this study, we have demonstrated and confirmed this role of RNF11 in
      microglia, the immune cells of the CNS. Coimmunoprecipitation experiments showed
      that RNF11 and A20 interact in a microglial cell line, suggesting the presence of
      A20 ubiquitin-editing protein complex in microglial cells. Next, using targeted
      short hairpin RNA (shRNA) knockdown and over-expression of RNF11, we established
      that RNF11 expression levels are inversely related to NF-kappaB activation, as
      evident from altered expression of NF-kappaB transcribed genes. Moreover our
      studies, illustrated that RNF11 confers protection against LPS-induced cell
      cytotoxicity. Thus our investigations clearly demonstrated that microglial RNF11
      is a negative regulator of NF-kappaB signalling pathway and could be a strong
      potential target for modulating inflammatory responses in neurodegenerative
      diseases.

PMID- 22975137
TI  - Differential expression of NMDA receptors in serotonergic and/or GABAergic
      neurons in the midbrain periaqueductal gray of the mouse.
AB  - N-methyl-d-aspartate (NMDA) receptors expressed in the midbrain periaqueductal
      gray (PAG) exert various physiological functions. The PAG contains various
      neurotransmitter phenotypes, which include GABAergic neurons and serotonergic
      neurons. In the present experiments, we made tight-seal whole-cell recordings
      from GABAergic and/or serotonergic neurons in mouse PAG slices and analyzed NMDA
      and non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) evoked by
      electrical stimulation. The NMDA/non-NMDA ratio of EPSC amplitude was high and
      the decay time course of NMDA-EPSC was slow in non-serotonergic/GABAergic
      neurons. In contrast, serotonergic neurons exhibited a low NMDA/non-NMDA ratio
      and a fast decay time course of NMDA-EPSC. Peripheral nerve ligation-induced
      chronic pain was associated with an increased NMDA/non-NMDA ratio in serotonergic
      neurons. Additionally, single-cell real-time RT-PCR analysis showed that
      peripheral nerve ligation up-regulated NR2B subunit expression in non
      serotonergic/non-GABAergic neurons. Such changes in NMDA receptor expression in
      the PAG result in an alteration of the descending modulation of nociception,
      which might be an underlying mechanism for peripheral nerve injury-evoked
      persistent pain. Finally, the expression of NMDA receptors seems differentially
      regulated among neurons of different neurotransmitter phenotypes in the PAG.

PMID- 22975138
TI  - Situational analysis of nursing education and work force in India.
AB  - Nursing care has been mentioned in the Indian culture from the times of the
      Vedas. However, according to World Health Organization, the nursing workforce in
      India is still insufficient to meet the needs of the country. The purpose of this
      article is to examine the status of nursing education and the nursing workforce
      in India and the challenges faced by the profession. Data supporting the
      statements made in the article were obtained from the Nursing Council of India,
      the Ministry of Health and Family Welfare, the Government of India Web sites,
      printed journals and communication with experts in the field. In India, there is
      a need to train approximately a million nurses to meet the current shortfall of
      health workers in the country. The nursing "brain drain" suggests that it may be
      one of the factors responsible for this shortfall. Further, nursing education
      faces challenges, such as streamlining nursing education, enriching the
      curriculum, strengthening faculty development and increasing the use of
      innovative teaching and learning techniques.

PMID- 22975139
TI  - Racial and ethnic identity in nursing research.
AB  - Nurse researchers need to be able to identify the race and ethnicity of
      participants in their studies for several reasons including addressing health
      disparities, ensuring adequate representation from under-represented minorities,
      and making sure other nurses can understand how findings may or may not pertain
      to their own patient population. However, obtaining accurate information about
      race and ethnicity requires careful attention to norms of study participants.
      Race and ethnicity are not always viewed as 2 separate constructs and the
      definition of both changes over time. In fact, a random sample of 100 patients in
      1 hospital found an 11% discrepancy between patients' self-identification of race
      using 2 different methodologies of self-identification. To optimize accuracy of
      self-identification of race and ethnicity, this paper discusses techniques
      learned in practice and in the literature for improving self-identification of
      these 2 constructs.

PMID- 22975140
TI  - Structural insights into serine protease inhibition by a marine invertebrate BPTI
      Kunitz-type inhibitor.
AB  - Proteins isolated from marine invertebrates are frequently characterized by
      exceptional structural and functional properties. ShPI-1, a BPTI Kunitz-type
      inhibitor from the Caribbean Sea anemone Stichodactyla helianthus, displays
      activity not only against serine-, but also against cysteine-, and aspartate
      proteases. As an initial step to evaluate the molecular basis of its activities,
      we describe the crystallographic structure of ShPI-1 in complex with the serine
      protease bovine pancreatic trypsin at 1.7A resolution. The overall structure and
      the important enzyme-inhibitor interactions of this first invertebrate BPTI-like
      Kunitz-type inhibitor:trypsin complex remained largely conserved compared to
      mammalian BPTI-Kunitz inhibitor complexes. However, a prominent stabilizing role
      within the interface was attributed to arginine at position P3. Binding free
      energy calculations indicated a 10-fold decrease for the inhibitor affinity
      against trypsin, if the P3 residue of ShPI-1 is mutated to alanine. Together with
      the increased role of Arg(11) at P3 position, slightly reduced interactions at
      the prime side (Pn') of the primary binding loop and at the secondary binding
      loop of ShPI-1 were detected. In addition, the structure provides important
      information for site directed mutagenesis to further optimize the activity of
      rShPI-1A for biotechnological applications.

PMID- 22975141
TI  - Myonecrosis by Clostridium septicum in a dog, diagnosed by a new multiplex-PCR.
AB  - Clostridial myositis is an acute, generally fatal toxemia that is considered to
      be rare in pet animals. The present report describes an unusual canine
      clostridial myositis that was diagnosed by a new multiplex-PCR (mPCR) designed
      for simultaneous identification of Clostridium sordellii, Clostridium septicum,
      Clostridium perfringens type A, Clostridium chauvoei, and Clostridium novyi type
      A. A ten-month-old male Rottweiler dog, that had displayed lameness and swelling
      of the left limb for 12 h, was admitted to a veterinary hospital. The animal was
      weak, dyspneic and hyperthermic, and a clinical examination indicated the
      presence of gas and edema in the limb. Despite emergency treatment, the animal
      died in only a few minutes. Samples of muscular tissue from the necrotic area
      were aseptically collected and plated onto defibrinated sheep blood agar (5%) in
      anaerobic conditions. Colonies suggestive of Clostridium spp. were submitted to
      testing by multiplex-PCR. Impression smears of the tissues, visualized with Gram
      and also with panoptic stains, revealed long rod-shaped organisms, and specimens
      also tested positive using the fluorescent antibody technique (FAT). The FAT and
      mPCR tests enabled a diagnosis of C. septicum myonecrosis in the dog.

PMID- 22975142
TI  - Continuity and discontinuity of trouble sleeping behaviors from early childhood
      to young adulthood in a large Australian community-based-birth cohort study.
AB  - OBJECTIVE: To examine the continuity and discontinuity of trouble sleeping
      behaviors (TSB) from childhood to adolescence and young adulthood in a community
      based prospective birth cohort study. METHODS: The original study comprised 7223
      mother-offspring pairs who were followed prospectively at pregnancy, 6 months, 5,
      14 and 21 years post-delivery. Participant numbers differ by follow-up stages.
      There were 3184 offspring for whom we have consistently collected information on
      TSB retrospectively at 2-4 years, and prospectively at 14 and 21 years of age.
      RESULTS: These comprised maternal-reported offspring TSB at 2-4 years and 14
      years, and offspring-reported trouble sleeping at 14 and 21 years. One in two
      children had persistent trouble sleeping from 2-4 to 14 years and two-thirds from
      14 to 21 years. In the adjusted analysis, compared with 2-4-years-old children
      with no trouble sleeping, those who experienced trouble sleeping were 1.20 (95%
      CI: 1.00, 1.44) times more likely to have trouble sleeping at 21 years.
      Similarly, adolescents who experienced trouble sleeping were 1.94 (95% CI: 1.66,
      2.27) times more likely to experience trouble sleeping at 21 years. CONCLUSIONS:
      There is a continuity of TSB from early childhood through adolescence and young
      adulthood, although the persistence of TSB is strongest from adolescence to young
      adulthood. Interventions improving sleep in young children may prevent longer
      term difficulties in adolescents and young adults.

PMID- 22975143
TI  - Zebrafish (Danio rerio) as a model for investigating dietary toxic effects of
      deoxynivalenol contamination in aquaculture feeds.
AB  - The effects of feeding six diets spiked with increasing levels of DON for 45 days
      to zebrafish (Danio rerio) on performance and liver gene biomarkers were
      investigated. In addition long term effects on fecundity, offspring larvae
      swimming activity and global DNA methylation in embryos were investigated.
      Zebrafish performance was not affected. Liver CYP1A mRNA levels were
      significantly higher in fish fed 2.0 ppm DON compared to the control group, 0.1,
      0.5 and 1.5 ppm group. Gene transcripts of CuZn SOD and Cyclin G1 increased with
      increasing content of dietary DON. The percentage of 5-methylcytosine in embryos
      did not differ and was 7.0-7.1% across the groups. Fecundity showed a biphasic
      response pattern. Interestingly, fish fed 1.5 ppm DON had 22% higher fecundity
      compared to control. A trend towards increased larvae swimming activity was seen
      in the high DON group. Our data suggest that DON is detoxified in the liver
      through the phase 1 system resulting in a disturbance in the oxidative balance.
      We do not know if effects observed on fecundity and larvae swimming activity are
      attributed to a direct interaction of DON with the reproductive organ or
      secondary to the maternal/paternal liver oxidative imbalance.

PMID- 22975144
TI  - Lactobacillus reuteri CRL 1098 and Lactobacillus acidophilus CRL 1014 differently
      reduce in vitro immunotoxic effect induced by Ochratoxin A.
AB  - Ochratoxin A (OTA) is a widespread mycotoxin contaminating several food products
      which causes detrimental health effects. The ability of Lactobacillus reuteri CRL
      1098 and Lactobacillus acidophilus CRL 1014 to prevent OTA effects on TNF-alpha
      and IL-10 production and apoptosis induction in human peripheral blood
      mononuclear cells (PBMC) was investigated. Membrane rafts participation in these
      responses was also evaluated. L. reuteri reduced by 29% the OTA inhibition of TNF
      alpha production whereas L. acidophilus increased 8 times the TNF-alpha
      production by OTA treated-PBMC. Also, both bacteria reversed apoptosis induced by
      OTA by 32%. However, neither of the bacteria reversed the OTA inhibition on IL-10
      production. On the other hand, the lactobacilli were less effective to reverse
      OTA effects on disrupted-rafts PBMC. This study shows that two lactobacilli
      strains can reduce some negative OTA effects, being membrane rafts integrity
      necessary to obtain better results. Also, the results highlight the potential
      capacity of some lactobacilli strains usually included in natural dietary
      components in milk-derived products and cereals feed, to reduce OTA toxicity once
      ingested by humans or animals.

PMID- 22975145
TI  - Evaluating cell specific cytotoxicity of differentially charged silver
      nanoparticles.
AB  - Silver nanoparticles (AgNPs) are one of the most commercially viable
      nanotechnological products, nevertheless; safety issues are raised regarding the
      use of such nanoparticles due to unintentional health and environmental impacts.
      In the present study, AgNPs were synthesized by chemically reducing silver
      nitrate alternatively with sodium borohydride, tannic acid, ascorbic acid and
      sodium citrate. AgNPs synthesized by reduction with tannic acid (TSNPs) and
      sodium borohydride (BSNPs) exhibited highest and lowest surface potential
      respectively. Therefore these two types of AgNPs were selected for their toxicity
      assessment in cellular environment. We treated skin epithelial A431, lung
      epithelial A549 and murine macrophages RAW264.7 cells with AgNPs over a range of
      doses (5-100MUg/ml). Toxicity was evaluated by measuring changes in cellular
      morphology, ROS generation, metabolic activity and expression of various stress
      markers. Interestingly, TSNPs exhibited a higher negative zeta-potential and also
      higher toxicity. Higher toxicity of TSNPs was attested by dose-dependent increase
      in cellular disruption and ROS generation. BSNPs showed cytotoxic effect up to
      the concentration of 50MUg/ml and thereafter the cytotoxic effect attenuated.
      TSNPs induced a dose dependent increase in the expression of stress markers pp38,
      TNF-alpha and HSP-70. Our report proposes that cytotoxicity of AgNPs changes with
      surface potential of nanoparticles and cells type.

PMID- 22975146
TI  - alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA
      receptors.
AB  - Alpha (alpha)-asarone is a major effective compound isolated from the Chinese
      medicinal herb Acorus gramineus, which is widely used in clinical practice as an
      antiepileptic drug; however, its mechanism of action remains unclear. In this
      study, we have characterized the action of alpha-asarone on the excitability of
      rat hippocampal neurons in culture and on the epileptic activity induced by
      pentylenetetrazole or kainate injection in vivo. Under cell-attached
      configuration, the firing rate of spontaneous spiking was inhibited by
      application of alpha-asarone, which was maintained in the Mg(2+)-free solution.
      Under whole-cell configuration, alpha-asarone induced inward currents in a
      concentration-dependent manner with an EC(50) of 248 +/- 33 MUM, which was
      inhibited by a GABA(A) receptor blocker picotoxin and a competitive GABA(A)
      receptor antagonist bicuculline but not a specific glycine receptor inhibitor
      strychnine. Measurement of tonic GABA currents and miniature spontaneous
      inhibitory postsynaptic currents indicated that alpha-asarone enhanced tonic
      GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both
      pentylenetetrazole and kainate seizure models, alpha-asarone suppressed epileptic
      activity of mice by prolonging the latency to clonic and tonic seizures and
      reducing the mortality as well as the susceptibility to seizure in vivo
      presumably dependent on the activation of GABA(A) receptors. In summary, our
      results suggest that alpha-asarone inhibits the activity of hippocampal neurons
      and produces antiepileptic effect in central nervous system through enhancing
      tonic GABAergic inhibition.

PMID- 22975147
TI  - Galectin-3 is essential for reactive oxygen species production by peritoneal
      neutrophils from mice infected with a virulent strain of Toxoplasma gondii.
AB  - Toxoplasma gondii stimulates a potent pro-inflammatory response and neutrophils
      are involved in early infection. Galectin-3 (Gal-3) is an endogenous modulator of
      inflammatory processes and anti-infective agents, but its interaction with
      neutrophils in T. gondii infection is still unclear. Here, we evaluated the role
      of Gal-3 in peritoneal inflammation, reactive oxygen species (ROS) production by
      neutrophils and survival, after in vivo T. gondii infection with virulent RH
      strain, using Gal-3 deficient and wild type mice. Animals were inoculated with
      thioglycollate or tachyzoites, and peritoneal cells were harvested for analysis
      of the influx of leukocytes. Neutrophils were isolated from peritoneal exudates
      from infected mice and stimulated with phorbol myristate acetate (PMA) to
      evaluate ROS production by luminol-dependent chemiluminescence assay. Our results
      showed that: (1) Gal-3 upregulates peritoneal inflammation, with enhanced
      recruitment of neutrophils and lymphocytes after thioglycollate stimulation, but
      does not influence the enhanced neutrophil influx after early T. gondii
      infection; (2) Gal-3 upregulates ROS generation by inflammatory peritoneal
      neutrophils from infected mice, but downregulates its production in non-infected
      mice and (3) Gal-3 does not influence the survival of mice after infection with
      the virulent T. gondii strain. In conclusion, Gal-3 is essential for ROS
      generation by neutrophils in the initial acute phase of T. gondii infection and
      this phenomenon may constitute an attempt to control parasite growth during in
      vivo infection with the T. gondii virulent strain.

PMID- 22975148
TI  - Use of explicit memory cues following parietal lobe lesions.
AB  - The putative role of the lateral parietal lobe in episodic memory has recently
      become a topic of considerable debate, owing primarily to its consistent
      activation for studied materials during functional magnetic resonance imaging
      studies of recognition. Here we examined the performance of patients with
      parietal lobe lesions using an explicit memory cueing task in which probabilistic
      cues ("Likely Old" or "Likely New"; 75% validity) preceded the majority of verbal
      recognition memory probes. Without cues, patients and control participants did
      not differ in accuracy. However, group differences emerged during the "Likely
      New" cue condition with controls responding more accurately than parietal
      patients when these cues were valid (preceding new materials) and trending
      towards less accuracy when these cues were invalid (preceding old materials).
      Both effects suggest insufficient integration of external cues into memory
      judgments on the part of the parietal patients whose cued performance largely
      resembled performance in the complete absence of cues. Comparison of the parietal
      patients to a patient group with frontal lobe lesions suggested the pattern was
      specific to parietal and adjacent area lesions. Overall, the data indicate that
      parietal lobe patients fail to appropriately incorporate external cues of novelty
      into recognition attributions. This finding supports a role for the lateral
      parietal lobe in the adaptive biasing of memory judgments through the integration
      of external cues and internal memory evidence. We outline the importance of such
      adaptive biasing through consideration of basic signal detection predictions
      regarding maximum possible accuracy with and without informative environmental
      cues.

PMID- 22975149
TI  - Experimental acquisition, development, and transmission of Leishmania tropica by
      Phlebotomus duboscqi.
AB  - We report experimental infection and transmission of Leishmania tropica (Wright),
      by the blood-feeding sand fly Phlebotomus duboscqi (Neveu-Lemaire). Groups of
      laboratory-reared female sand flies that fed "naturally" on L. tropica-infected
      hamsters, or artificially, via membrane feeding device, on a suspension of L.
      tropica amastigotes, were dissected at progressive time points post-feeding.
      Acquisition, retention and development of L. tropica through procyclic,
      nectomonad, and leptomonad stages to the infective metacyclic promastigote stage,
      and anterior progression of the parasites from abdominal midgut bloodmeal to the
      thoracic midgut were demonstrated in both groups. Membrane feeding on the
      concentrated amastigote suspension led to metacyclic promastigote infections in
      60% of sand flies, whereas only 3% of P. duboscqi that fed naturally on an
      infected hamster developed metacyclics. Sand flies from both groups re-fed on
      naive hamsters, but despite infections in 25-50% of membrane-fed and 2-3.5% of
      naturally fed flies, no skin lesions developed in the hamsters. After four months
      of observation these animals were euthanized and necropsied. Screening of the
      organs and tissue by polymerase chain reaction (PCR) that targeted the small
      subunit RNA gene, amplified generic Leishmania DNA from liver, spleen, bone
      marrow, and blood, but only from hamsters bitten by membrane-infected P.
      duboscqi. These results are notable in demonstrating the ability of P. duboscqi,
      originating from Kenya, to acquire, retain, develop, and transmit a Turkish
      strain of L. tropica originally isolated from a human case of cutaneous
      leishmaniasis. This marks the first demonstration of complete development and
      transmission of L. tropica by a member of the Phlebotomus subgenus of sand flies.

PMID- 22975150
TI  - Accuracy and consequences of 3D-fluoroscopy in upper and lower extremity fracture
      treatment: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to compare the diagnostic
      accuracy, subjective image quality and clinical consequences of 3D-fluoroscopy
      with standard imaging modalities (2D-fluoroscopy, X-ray or CT) during reduction
      and fixation of intra-articular upper and lower extremity fractures. METHODS: A
      systematic literature search was performed in MEDLINE, EMBASE and the Cochrane
      library. In total 673 articles were identified (up to March 2012). The 19
      included studies described patients/cadavers with intra-articular upper/lower
      extremity fractures and compared 3D-fluoroscopy to standard imaging. The study
      was performed in accordance with the Quality Assessment of Diagnostic Accuracy
      Studies (QUADAS) guidelines. Diagnostic accuracy was defined by the quality of
      fracture reduction or implant position and, if possible, expressed as sensitivity
      and specificity; subjective image quality was determined by the quality of
      depiction of bone or implants; clinical consequences were defined as corrections
      in reduction or implant position following 3D-fluoroscopy. RESULTS: Ten cadaver-
      and nine clinical studies were included. A meta-analysis was not possible,
      because studies used different scoring protocols to express diagnostic accuracy
      and reported incomplete data. Based on the individual studies, diagnostic
      accuracy of 3D-fluoroscopy was better than 2D-fluoroscopy and X-ray, but similar
      to CT-scanning. Subjective image quality of 3D-fluoroscopy was inferior compared
      to all other imaging modalities. In 11-40% of the operations additional
      corrections were performed after 3D-fluoroscopy, while the necessity for these
      corrections were not recognized based on 2D-fluoroscopic images. CONCLUSIONS:
      Although subjective image quality is rated inferior compared to other imaging
      modalities, intra-operative use of 3D-fluoroscopy is a helpful diagnostic tool
      for improving the quality of reduction and implant position in intra-articular
      fractures.

PMID- 22975151
TI  - Assessment of the relationship between drowning and fluid accumulation in the
      paranasal sinuses on post-mortem computed tomography.
AB  - Recent reports have detailed common computed tomography (CT) findings in drowning
      victims, most notably fluid accumulation in the maxillary and sphenoidal sinuses.
      This CT finding could help forensic doctors to diagnose drowning. This study
      retrospectively investigated 151 subjects: 39 drowning and 112 non-drowning
      cases. Pearson's chi-square tests demonstrated that fluid accumulation in the
      maxillary or sphenoidal sinuses was associated significantly with drowning
      (p=0.0001). The sensitivity of the drowning diagnosis was 97%, specificity was
      35%, accuracy was 51%, positive predictive value was 34% and negative predictive
      value was 98%. Drowning was significantly associated with fluid accumulation in
      the maxillary and sphenoidal sinuses, but the specificity and positive predictive
      value of the drowning diagnosis were poor. Although the presence of fluid in the
      maxillary and sphenoidal sinuses cannot be used to diagnose drowning, the absence
      of the fluid can be used to virtually exclude drowning.

PMID- 22975152
TI  - Pangenomics--an avenue to improved industrial starter cultures and probiotics.
AB  - With the dramatic reductions in the cost and time involved in DNA sequencing, a
      new approach to characterisation of bacteria is emerging. It is based on a
      comparison of complete genome sequences of a number of members of the same
      species (pangenomics). Pangenomics opens an array of new opportunities for
      understanding and improving industrial starter cultures and probiotics. These
      include understanding the formation of texture and flavour in dairy products,
      understanding the functionality of probiotics as well as providing information
      that can be used for strain screening, strain improvement, safety assessments and
      process improvements.

PMID- 22975153
TI  - Hydroxyl radical's role in the remediation of wastewater.
AB  - The photocatalytic degradation of wastewater with ZnO based photocatalysts under
      solar illumination has been investigated. Advanced oxidation processes such as
      photoelectrocatalysis, sonolysis and H(2)O(2) treatment show promise in
      eliminating the dangers of exposure to wastewater and the products of their
      natural breakdown. A basic understanding of the mechanistic details involved in
      the oxidative transformations remains the key for improving the effectiveness of
      the advanced oxidation processes. The role of hydroxyl radical in the breakdown
      of the wastewater is elucidated through determining the degradation rates,
      analyzing transformation intermediates and studies using computational chemistry
      methods. In order to realize a complete mineralization of wastewater COD, BOD and
      TOC analysis has been carried out.

PMID- 22975154
TI  - Macrophage subtypes in symptomatic carotid artery and femoral artery plaques.
AB  - OBJECTIVE: To compare differences in macrophage heterogeneity and morphological
      composition between atherosclerotic plaques obtained from recently symptomatic
      patients with carotid artery disease and femoral plaques from patients with
      severe limb ischemia. DESIGN: Experimental study. METHODS: Plaques were obtained
      from 32 patients undergoing carotid endarterectomy and 25 patients undergoing
      common femoral endarterectomy or lower limb bypass. Macrophages and T cell
      numbers were detected in plaque sections by immunohistochemistry and anti CD68
      and CD3 antibodies. Dual staining for CD68 and M1- and M2-macrophage markers and
      morphometric analysis of hematoxylin and eosin stained plaque sections was
      performed. RESULTS: Carotid plaques had significantly increased percentage areas
      of confluent lipid and leukocytic infiltrates. In contrast, areas of
      fibroconnective tissue were significantly greater in femoral plaques and
      percentage areas of confluent calcification and collagen were elevated. Carotid
      artery plaques had greater numbers per plaque area of macrophages and T cells
      consistent with a more inflammatory phenotype. Proportions displaying M1
      activation markers were significantly increased in the carotid compared to
      femoral plaques whereas femoral plaques displayed a greater proportion of M2
      macrophages. CONCLUSION: Plaques from patients with recently symptomatic carotid
      disease have a predominance of M1-macrophages and higher lipid content than
      femoral plaques, consistent with a more unstable plaque.

PMID- 22975155
TI  - Mechanism of interaction of novel uncharged, centrally active reactivators with
      OP-hAChE conjugates.
AB  - A library of more than 200 novel uncharged oxime reactivators was used to select
      and refine lead reactivators of human acetylcholinesterase (hAChE) covalently
      conjugated with sarin, cyclosarin, VX, paraoxon and tabun. N-substituted 2
      hydroxyiminoacetamido alkylamines were identified as best reactivators and
      reactivation kinetics of the lead oximes, RS41A and RS194B, were analyzed in
      detail. Compared to reference pyridinium reactivators, 2PAM and MMB4, molecular
      recognition of RS41A reflected in its Kox constant was compromised by an order of
      magnitude on average for different OP-hAChE conjugates, without significant
      differences in the first order maximal phosphorylation rate constant k(2).
      Systematic structural modifications of the RS41A lead resulted in several-fold
      improvement with reactivator, RS194B. Kinetic analysis indicated K(ox) reduction
      for RS194B as the main kinetic constant leading to efficient reactivation. Subtle
      structural modifications of RS194B were used to identify essential determinants
      for efficient reactivation. Computational molecular modeling of RS41A and RS194B
      interactions with VX inhibited hAChE, bound reversibly in Michaelis type complex
      and covalently in the pentacoordinate reaction intermediate suggests that the
      faster reactivation reaction is a consequence of a tighter RS194B interactions
      with hAChE peripheral site (PAS) residues, in particular with D74, resulting in
      lower interaction energies for formation of both the binding and reactivation
      states. Desirable in vitro reactivation properties of RS194B, when coupled with
      its in vivo pharmacokinetics and disposition in the body, reveal the potential of
      this oxime design as promising centrally and peripherally active antidotes for OP
      toxicity.

PMID- 22975156
TI  - EGFR mutations and human papillomavirus in lung cancer.
AB  - Our previous study reported a frequent detection of human papillomavirus (HPV)
      genome in primary lung adenocarcinomas of the recurrent patients who were
      responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor,
      suggesting that HPV presence in lung cancer may be related to a genetic
      background related to EGFR mutations. The present study examined the association
      between the HPV presence and mutations in exons 19 and 21 of EGFR gene in
      Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations.
      Although these mutations were tended to be observed in females, non-smokers, or
      adenocarcinomas, there was no statistically significant associations. HPV DNA was
      found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in
      histological types. The presence of HPV DNA was significantly related to EGFR
      mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV
      positive lung tumors accounted for 38% and 7% of those with and without EGFR
      mutations, respectively. Our results suggest that EGFR mutations are associated
      with HPV presence in Japanese patients with lung cancer.

PMID- 22975157
TI  - Procedural justice and quality of life in compensation processes.
AB  - BACKGROUND: There is considerable evidence that being involved in compensation
      processes has a negative impact on claimants' health. Previous studies suggested
      that this negative effect is caused by a stressful compensation process:
      claimants suffered from a lack of communication, a lack of information, and
      feelings of distrust. However, these rather qualitative findings have not been
      quantitatively investigated yet. This observational study aimed to fill this gap
      of knowledge, investigating the claimants' perceived fairness of the compensation
      process, the provided information, and the interaction with lawyers and insurance
      companies, in relation to the claimants' quality of life. METHOD: Participants
      were individuals injured in traffic accidents, older than 18 years, who were
      involved in a compensation process in the Netherlands. They were recruited by
      three claims settlement offices. Outcome measures were procedural, interactional,
      and informational justice, and quality of life. RESULTS: Participants (n=176)
      perceived the interaction with lawyers to be fairer than the interaction with
      insurance companies (p<.001). The length of hospital stay was positively
      associated with procedural justice (beta=.31, p<.001). Having trunk/back injury
      was negatively related to procedural justice (beta=-.25, p=.001). Whiplash injury
      and length of time involved in the claim process were not associated with any of
      the justice scales. Finally, procedural justice was found to be positively
      correlated with quality of life (rs=.22, p=.004). DISCUSSION: The finding that
      the interaction with insurance companies was considered less fair than the
      interaction with lawyers may imply that insurers could improve their interaction
      with claimants, e.g. by communicating more directly. The result that claimants
      with mild injuries and with trunk/back injuries considered the compensation
      process to be less fair than those with respectively severe injuries and injuries
      to other body parts suggests that especially the former two require an attentive
      treatment. Finally, the fact that procedural justice was positively correlated
      with quality of life could implicate that it is possible to improve claimants'
      health in compensation processes by enhancing procedural justice, e.g. by
      increasing the ability for claimants to express their views and feelings and by
      involving claimants in the decision-making process.

PMID- 22975158
TI  - A control point interpolation method for the non-parametric quantification of
      cerebral haemodynamics from dynamic susceptibility contrast MRI.
AB  - DSC-MRI analysis is based on tracer kinetic theory and typically involves the
      deconvolution of the MRI signal in tissue with an arterial input function (AIF),
      which is an ill-posed inverse problem. The current standard singular value
      decomposition (SVD) method typically underestimates perfusion and introduces non
      physiological oscillations in the resulting residue function. An alternative
      vascular model (VM) based approach permits only a restricted family of shapes for
      the residue function, which might not be appropriate in pathologies like stroke.
      In this work a novel deconvolution algorithm is presented that can estimate both
      perfusion and residue function shape accurately without requiring the latter to
      belong to a specific class of functional shapes. A control point interpolation
      (CPI) method is proposed that represents the residue function by a number of
      control points (CPs), each having two degrees of freedom (in amplitude and time).
      A complete residue function shape is then generated from the CPs using a cubic
      spline interpolation. The CPI method is shown in simulation to be able to
      estimate cerebral blood flow (CBF) with greater accuracy giving a regression
      coefficient between true and estimated CBF of 0.96 compared to 0.83 for VM and
      0.71 for the circular SVD (oSVD) method. The CPI method was able to accurately
      estimate the residue function over a wide range of simulated conditions. The CPI
      method has also been demonstrated on clinical data where a marked difference was
      observed between the residue function of normally appearing brain parenchyma and
      infarcted tissue. The CPI method could serve as a viable means to examine the
      residue function shape under pathological variations.

PMID- 22975159
TI  - Studying the topological organization of the cerebral blood flow fluctuations in
      resting state.
AB  - In this paper the cerebral blood flow (CBF) in resting state obtained from SPECT
      imaging is employed as a hemodynamics descriptor to study the concurrent changes
      between brain structures and to build binarized connectivity graphs. The
      statistical similarity in CBF between pairs of regions was measured by computing
      the Pearson correlation coefficient across 31 normal subjects. We demonstrated
      the CBF connectivity matrices follow 'small-world' attributes similar to previous
      studies using different modalities of neuroimaging data (MRI, fMRI, EEG, MEG).
      The highest concurrent fluctuations in CBF were detected between homologous
      cortical regions (homologous callosal connections). It was found that the
      existence of structural core regions or hubs positioned on a high proportion of
      shortest paths within the CBF network. These were anatomically distributed in
      frontal, limbic, occipital and parietal regions that suggest its important role
      in functional integration. Our findings point to a new possibility of using CBF
      variable to investigate the brain networks based on graph theory in normal and
      pathological states. Likewise, it opens a window to future studies to link
      covariation between morphometric descriptors, axonal connectivity and CBF
      processes with a potential diagnosis applications.

PMID- 22975160
TI  - Approaching expert results using a hierarchical cerebellum parcellation protocol
      for multiple inexpert human raters.
AB  - Volumetric measurements obtained from image parcellation have been instrumental
      in uncovering structure-function relationships. However, anatomical study of the
      cerebellum is a challenging task. Because of its complex structure, expert human
      raters have been necessary for reliable and accurate segmentation and
      parcellation. Such delineations are time-consuming and prohibitively expensive
      for large studies. Therefore, we present a three-part cerebellar parcellation
      system that utilizes multiple inexpert human raters that can efficiently and
      expediently produce results nearly on par with those of experts. This system
      includes a hierarchical delineation protocol, a rapid verification and evaluation
      process, and statistical fusion of the inexpert rater parcellations. The quality
      of the raters' and fused parcellations was established by examining their Dice
      similarity coefficient, region of interest (ROI) volumes, and the intraclass
      correlation coefficient of region volume. The intra-rater ICC was found to be
      0.93 at the finest level of parcellation.

PMID- 22975161
TI  - Simple and effective large-scale preparation of geniposide from fruit of Gardenia
      jasminoides Ellis using a liquid-liquid two-phase extraction.
AB  - Geniposide was prepared on a large-scale using a selective two-phase liquid
      liquid extraction. The aqueous residue from the fruit of Gardenia jasminoides
      Ellis was treated with sodium carbonate and extracted with n-butanol several
      times. The n-butanol extracts were treated with activated granular charcoal to
      remove pigments and were then concentrated to produce a residue with a high solid
      content. The residue was crystallized to obtain geniposide with 98% purity. For
      large-scale synthesis, the residue (solid content 45%, geniposide 5.5%) was
      extracted to generate 70g of geniposide with 98% purity and 84.8% recovery using
      1500g residue.

PMID- 22975162
TI  - Four new coumarinolignoids from seeds of Solanum indicum.
AB  - Activity-guided fractionation of seeds of Solanum indicum for anti-HBV activity
      led to the isolation of two novel coumarinolignoid alkaloids (indicumines A-B, 1
      2) and two new coumarinolignoids (indicumines C-D, 3-4), together with four known
      coumarins (5-8). Their structures were established on the basis of spectroscopic
      data. The two novel coumarinolignoid alkaloids shows anti-HBV activities through
      specifically inhibiting the secretion of HBsAg in HepG2.2.15.

PMID- 22975163
TI  - Manganese regulates caspase-3 gene promoter activity by inducing Sp1
      phosphorylation in PC12 cells.
AB  - Chronic manganese exposure causes selective toxicity to the dopaminergic system,
      resulting in a parkisonian-like neurological condition known as manganism.
      Manganese causes a typical apoptosis, which includes activation of the caspase
      cascade and DNA fragmentation in PC12 cells. Caspase-3 is a major contributor to
      the execution of neuronal apoptosis. In a previous study, we demonstrated that
      caspase-3 cleavage and expression of pro-caspase-3 mRNA and protein increased in
      PC12 cells treated with manganese, but this response was not observed with other
      apoptosis inducers. To understand the molecular mechanisms that regulate
      expression of caspase-3 in manganese-treated PC12 cells, we characterized the 5'
      flanking region of the rat caspase-3 gene and identified both a core promoter and
      a manganese-responsive region that contains three putative Sp1 binding sites.
      Furthermore, manganese treatment induced robust Sp1 phosphorylation and increased
      its DNA binding activity. Overexpression of mutant Sp1 lacking phosphorylation
      sites attenuated Sp1's ability to stimulate manganese-induced caspase-3 promoter
      activity. In conclusion, our results indicate that Sp1 phosphorylation is
      required for manganese-induced transactivation of caspase-3.

PMID- 22975164
TI  - Biotransformation of natural compounds: unexpected thio conjugation of Sch-642305
      with 3-mercaptolactate catalyzed by Aspergillus niger ATCC 16404 cells.
AB  - Sch-642305 is produced by the endophytic fungi Phomopsis sp. CMU-LMA and exhibits
      both antimicrobial and cytotoxic activities. The incubation of Sch-642305 with
      Aspergillus niger ATCC 16404 resting cells leads to two unexpected thio
      conjugates. Compound (1) is formed by the addition of the cysteine metabolite 3
      mercaptolactate to the double bond of Sch-642305. Compound (1) undergoes an
      intramolecular rearrangement to give compound (2), which contains two rings: a
      five-membered hydroxylactone ring and a five-membered thiophene ring. The
      absolute configuration of compound (1) is similar to that of the parent compound,
      but the configuration of the mercaptolactate side-chain was not determined. The
      absolute configuration of compound (2) was deduced from the crystal structure and
      confirmed by the anomal effect of the sulfur atom. To the best of our knowledge,
      this is the first time such a conjugation rearrangement reactions were observed.
      The biological significance and the reaction mechanisms are discussed. Compound
      (1) exhibits a weak antimicrobial activity against Gram-positive bacteria,
      whereas derivatives (1) and (2) showed an IC50 of 1 and 1.2 MUM, respectively,
      against colonic epithelial cancer cells.

PMID- 22975166
TI  - Austrian syndrome in the context of a fulminant pneumococcal native valve
      endocarditis.
AB  - This is the case of a young male suffering from Austrian syndrome, which is the
      triad of endocarditis, meningitis, and pneumonia due to invasive S. pneumoniae
      infection. He reported recurrent fever for six months without any antibiotic
      treatment, which may have determined the further course of the syndrome.
      Echocardiography revealed massive native valve endocarditis, and the patient was
      considered for ultima-ratio cardiac surgery. Intraoperative aspect presented
      extensive affection of the aortic root with full destruction of aortic valve,
      mitral valve, and aortomitral continuity. The myocardium showed a phlegmon-like
      infiltration. Microbiologic testing of intraoperatively collected specimens
      identified penicillin-sensitive Streptococcus pneumoniae. S. pneumoniae is a very
      uncommon cause for infective infiltrative endocarditis and is associated with
      severe clinical courses. Austrian syndrome is even more rare, with only a few
      reported cases worldwide. In those patients, only early diagnosis, immediate
      antibiotic treatment, and emergent cardiac surgery can save lives.

PMID- 22975165
TI  - Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+T cells after
      autologous transplantation for myeloma.
AB  - The number of circulating lymphocytes on day 15 after transplantation correlates
      with improved survival in patients with myeloma, but the lymphocyte subset
      responsible is unknown. NKG2D is a natural killer (NK) cell activating receptor
      that mediates non-MHC restricted and TCR-independent cell lysis. Our preliminary
      results indicate that CD3(+)CD8(+) T cells expressing NKG2D may be a critical
      lymphocyte population. A phase II trial examined the feasibility of infusing ex
      vivo-expanded cells enriched for NKG2D(+)CD3(+)CD8(+) T cells at weeks 1, 2, 4,
      and 8 after an autologous transplantation. In addition, low-dose IL-2 (6 * 10(5)
      IU/m(2)/day) was administered for 4 weeks, beginning on the day of
      transplantation. Twenty-three patients were accrued and 19 patients are
      evaluable. There were no treatment-related deaths. All patients completed their
      course of IL-2 and demonstrated normal engraftment. When compared with patients
      with myeloma who underwent transplantation not receiving posttransplantation
      immune therapy, the treated patients demonstrated an increase in the number of
      circulating NKG2D(+)CD3(+)CD8(+) T cells/MUL (P < .004), CD3(+)CD8(+) T cells/MUL
      (P < .04), CD3(+)CD8(+)CD56(+) T cells/MUL (P < .004), and NKG2D(+)CD3(-)CD56(+)
      T cells/MUL (P < .003). Myeloma cell-directed cytotoxicity by the circulating
      mononuclear cells increased after transplantation (P < .002). When compared to
      posttransplantation IL-2 therapy alone in this patient population, the addition
      of cells enriched for NKG2D(+)CD3(+)CD8(+) T cells increased tumor-specific
      immunity, as demonstrated by enhanced lysis of autologous myeloma cells (P =
      .02). We postulate that this regimen that increased the number and function of
      the NKG2D(+)CD3(+)CD8(+) T cells after transplantation may improve clinical
      outcomes by eliminating residual malignant cells in vivo.

PMID- 22975167
TI  - Clinical and microbiological characterization of pneumonia in mechanically
      ventilated patients.
AB  - OBJECTIVE: To characterize mechanical ventilation-associated pneumonia (MVAP).
      METHOD: This is an observational descriptive study to characterize MVAP in 61
      ventilated patients admitted in the intensive care units of the Hermanos
      Ameijeiras hospital during 2011. This study also aimed to isolate the bacteria
      causing MVAP and characterize their resistance to antibiotics. RESULTS: 51
      (83.60%) patients presented pulmonary infiltrates and 35 (50.81%) presented a
      clinical score >= 6 according to the Clinical Pulmonary Infection Score.
      Acinetobacter baumannii and Pseudomonas aeruginosa were the most frequently
      isolated microorganisms from patients with MVAP. Both microorganisms showed a
      high resistance to antibiotics. Carbapenems were the most frequent used
      antimicrobial therapeutic agents; elective antibiotic combinations were directed
      against both bacterial wall structure and nucleic acid synthesis. CONCLUSION:
      Patients with MVAP identified during the studied period showed similar frequency
      to those reported in medical literature. Thus, this study corroborated that this
      is still a relevant medical problem in this hospital. Acinetobacter baumannii and
      Pseudomonas aeruginosa were the most frequently isolated microorganisms from
      patients with MVAP. Antimicrobial treatment, empirical or not, are still the main
      risk factors for the development of multidrug-resistant strains of bacteria. The
      rate of resistance to antibiotics of Acinetobacter baumannii and Pseudomonas
      aeruginosa strains isolated from patients with MVAP was higher than those
      isolated from infected patients without MAVP. Tigecycline and colistin were the
      only antibiotics fully effective against Acinetobacter baumannii strains isolated
      in 2011 from patients with MVAP; against Pseudomonas aeruginosa strains, only
      colistin was fully effective.

PMID- 22975168
TI  - Antimicrobial resistance profile of pathogens isolated from blood cultures in
      public and private hospitals in Brazil.

PMID- 22975169
TI  - Phenotypic and genotypic characterization of Rhodococcus equi isolated from
      sputum.
AB  - INTRODUCTION: Rhodococcus equi is an opportunistic pathogen, causing
      rhodococcosis, a condition that can be confused with tuberculosis. Often, without
      identifying M. tuberculosis, physicians initiate empiric treatment for
      tuberculosis. R. equi and M. tuberculosis have different susceptibility to drugs.
      Identification of R. equi is based on a variety of phenotypic, chromatographic,
      and genotypic characteristics. OBJECTIVE: This study aimed to characterize
      bacterial isolates from sputum samples suggestive of R. equi. METHODS: The
      phenotypic identification included biochemical assays; thin-layer chromatography
      (TLC) and polymerase chain reaction (PCR) were used for genotypic identification.
      RESULTS: Among 78 Gram-positive and partially acid-fast bacilli isolated from the
      sputum of tuberculosis-suspected patients, 51 were phenotypically and
      genotypically characterized as R. equi based on literature data. Mycolic acid
      analysis showed that all suspected R. equi had compounds with a retention factor
      (R(f)) between 0.4-0.5. Genotypic characterization indicated the presence of the
      choE gene 959bp fragments in 51 isolates CAMP test positive. Twenty-two CAMP test
      negative isolates were negative for the choE gene. Five isolates presumptively
      identified as R. equi, CAMP test positive, were choE gene negative, and probably
      belonged to other bacterial species. CONCLUSIONS: The phenotypic and molecular
      techniques used constitute a good methodological tool to identify R. equi.

PMID- 22975170
TI  - Aeromycological study at the intensive care unit of the "Dr. Manuel Gea Gonzalez"
      General Hospital.
AB  - INTRODUCTION: An aeromycological study verifies the presence and quantifies the
      concentration of fungal propagules in the air. It is very important in the
      hospital setting because of the increasing numbers of immunosuppressed and
      severely ill patients. The objective of this study was to determine the
      concentration of fungi in the air of the intensive care unit (ICU) of "Dr. Manuel
      Gea Gonzalez" General Hospital. METHODS: This is a descriptive, observational
      cross-sectional study. Air samples were obtained with a single stage Thermo
      Andersen Viable Particle Sampler (Thermo Electron Corporation - Massachusetts,
      U.S.A.) in a Petri dish with potato dextrose agar for 15 minutes at two different
      times (morning and afternoon) and heights (1 and 1.5 meters). The Petri dishes
      were incubated for five to seven days at 27 degrees  C, the number of colonies
      was counted, and the total CFU/m(3) was determined. The isolated fungal genera
      were identified by morphological features. Epi Info v. 3.4.3 (c) was used for
      statistical analysis. RESULTS: The mean concentration of fungi in the air of the
      ICU was 85.08 +/- 29.19 CFU/m(3); while in the outside air it was 84.3 +/- 17.23
      CFU/m(3) (p = 0.96). The fungi isolated were: Cladosporium spp., Penicillium
      spp., Aspergillus spp. (non-fumigatus), Fusarium spp., Exophiala spp.,
      Syncephalastrum spp., and Acremonium spp. DISCUSSION: Fungal spores were found in
      the air of the ICU and Cladosporium spp. was the most frequently isolated fungi.
      There was no difference according to sampling time or height.

PMID- 22975171
TI  - Antibiotics produced by Streptomyces.
AB  - Streptomyces is a genus of Gram-positive bacteria that grows in various
      environments, and its shape resembles filamentous fungi. The morphological
      differentiation of Streptomyces involves the formation of a layer of hyphae that
      can differentiate into a chain of spores. The most interesting property of
      Streptomyces is the ability to produce bioactive secondary metabolites, such as
      antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants,
      and especially antibiotics. The production of most antibiotics is species
      specific, and these secondary metabolites are important for Streptomyces species
      in order to compete with other microorganisms that come in contact, even within
      the same genre. Despite the success of the discovery of antibiotics, and advances
      in the techniques of their production, infectious diseases still remain the
      second leading cause of death worldwide, and bacterial infections cause
      approximately 17 million deaths annually, affecting mainly children and the
      elderly. Self-medication and overuse of antibiotics is another important factor
      that contributes to resistance, reducing the lifetime of the antibiotic, thus
      causing the constant need for research and development of new antibiotics.

PMID- 22975172
TI  - First diagnostic cases of human babesiosis in Montenegro.

PMID- 22975173
TI  - Cytomegalovirus (CMV)-related cutaneous necrotizing vasculitis: case report and
      literature review.
AB  - Cytomegalovirus (CMV) infection is usually asymptomatic in immunocompetent
      patients. A mononucleosis-like syndrome may develop in some patients. Various
      organ involvements (e.g.: encephalitis, meningitis, retinitis, myocarditis,
      pneumonia, hepatitis, enterocolitis, neuritis), which rarely occur in
      immunocompetent patients, have also been reported. Cutaneous necrotizing
      vasculitis caused by CMV infection has been reported very rarely in the
      literature. Here, a case with a very rare clinical form of CMV infection,
      presenting with persistent fever and livedo reticularis on the extremities and
      cutaneous necrotizing vasculitis of the toes, is described, and the relevant
      literature is reviewed. This case report aims to highlight the possibility of CMV
      infection to be a cause of cutaneous necrotizing vasculitis.

PMID- 22975174
TI  - Epidemiological and clinical aspects of urinary tract infection in community
      dwelling elderly women.
AB  - BACKGROUND: Urinary tract infections (UTIs) in elderly patients can be a complex
      problem in terms of approach to diagnosis, treatment, and prevention, because the
      patients often present nonspecific symptoms. The epidemiological and clinical
      characteristics of UTI in elderly women were studied, in order to make early
      diagnosis and prevent serious clinical complications secondary to UTI. METHODS:
      This was a prospective population-based study, with elderly women, during their
      first medical office visit. Medical records were obtained by clinical history and
      physical examination in order to detect signs and symptoms of UTI and the
      presence of co-morbidities. Clean-catch midstream urine specimens for urinary
      dipstick test, sediment, and culture were collected; cervical samples for
      conventional Pap smears were also collected. RESULTS: UTI was found in 16.55% of
      elderly women. The most frequent urinary symptom was foul smelling urine, in
      60.6%. E. coli was responsible for 98 (76.56%) cases of significant bacteriuria;
      34 (34.69%) were resistant to trimethoprim-sulfamethoxazole, and 21 (21.42%) to
      fluoroquinolones. Asymptomatic bacteriuria (AB) was not treated. The presence of
      predisposing factors demonstrated that the history of previous UTI (p < 0.001),
      vaginitis (p < 0.001), and diabetes (p = 0.042) increased the risk for UTI.
      CONCLUSION: This study confirmed the high prevalence of UTI among elderly women
      and its unusual clinical presentation. Diabetes, history of previous UTI, and
      vaginitis were shown to be predisposing factors for UTI; it is not necessary to
      treat AB in elderly women, even among diabetics.

PMID- 22975175
TI  - Salvage treatment of disseminated strongyloidiasis in an immunocompromised
      patient: therapy success with subcutaneous ivermectin.
AB  - Disseminated strongyloidiasis is a disease with high mortality rate, especially
      in immunocompromised individuals. Paralytic ileus and intestinal malabsorption
      are frequent symptoms caused by this severe disease. As there are no licensed
      parenteral anthelmintic drugs for human use, off-label formulations are often
      used in the treatment of this disease. In this case report, the use of
      subcutaneous ivermectin is described as a successful therapy for this life
      threatening infection.

PMID- 22975176
TI  - Introducing nonlinear, multivariate 'Predictor Surfaces' for quantitative
      modeling of chemical systems with higher-order, coupled predictor variables.
AB  - Innovations in chemometrics are required for studies of chemical systems which
      are governed by nonlinear responses to chemical parameters and/or
      interdependencies (coupling) among these parameters. Conventional and linear
      multivariate models have limited use for quantitative and qualitative
      investigations of such systems because they are based on the assumption that the
      measured data are simple superpositions of several input parameters. 'Predictor
      Surfaces' were developed for studies of more chemically complex systems such as
      biological materials in order to ensure accurate quantitative analyses and proper
      chemical modeling for in-depth studies of such systems. Predictor Surfaces are
      based on approximating nonlinear multivariate model functions by multivariate
      Taylor expansions which inherently introduce the required coupled and higher
      order predictor variables. As proof-of-principle for the Predictor Surfaces'
      capabilities, an application from environmental analytical chemistry was chosen.
      Microalgae cells are known to sensitively adapt to changes in environmental
      parameters such as pollution and/or nutrient availability and thus have potential
      as novel in situ sensors for environmental monitoring. These adaptations of the
      microalgae cells are reflected in their chemical signatures which were then
      acquired by means of FT-IR spectroscopy. In this study, the concentrations of
      three nutrients, namely inorganic carbon and two nitrogen containing ions, were
      chosen. Biological considerations predict that changes in nutrient availability
      produce a nonlinear response in the cells' biomass composition; it is also known
      that microalgae need certain nutrient mixes to thrive. The nonlinear Predictor
      Surfaces were demonstrated to be more accurate in predicting the values of these
      nutrients' concentrations than principal component regression. For qualitative
      chemical studies of biological systems, the Predictor Surfaces themselves are a
      novel tool as they visualize nonlinearities and more importantly the coupling
      among predictor variables. Thus, they can serve as a novel tool for studies in
      bioanalytical chemistry, biology, and ecology.

PMID- 22975177
TI  - Sample preparation methods for subsequent determination of metals and non-metals
      in crude oil--a review.
AB  - In this review sample preparation strategies used for crude oil digestion in last
      ten years are discussed focusing on further metals and non-metals determination.
      One of the main challenges of proposed methods has been to overcome the
      difficulty to bring crude oil samples into solution, which should be compatible
      with analytical techniques used for element determination. On this aspect, this
      review summarizes the sample preparation methods for metals and non metals
      determination in crude oil including those based on wet digestion, combustion,
      emulsification, extraction, sample dilution with organic solvents, among others.
      Conventional methods related to wet digestion with concentrated acids or
      combustion are also covered, with special emphasis to closed systems. Trends in
      sample digestion, such as microwave-assisted digestion using diluted acids
      combined with high-efficiency decomposition systems are discussed. On the other
      hand, strategies based on sample dilution in organic solvents and procedures
      recommended for speciation analysis are reported as well as the use of direct
      analysis in view of the recent importance for crude oil field. A compilation
      concerning sample preparation for crude oil provided by official methods as well
      as certified reference materials available for accuracy evaluation is also
      presented and discussed.

PMID- 22975178
TI  - Insights into information contained in multiplicative scatter correction
      parameters and the potential for estimating particle size from these parameters.
AB  - This paper investigates the nature of information contained in scatter correction
      parameters. The study had two objectives. The first objective was to examine the
      nature and extent of information contained in scatter correction parameters. The
      second objective is to examine whether this information can be effectively
      extracted by proposing a method to obtain particularly the mean particle diameter
      from the scatter correction parameters. By using a combination of experimental
      data and simulated data generated using fundamental light propagation theory, a
      deeper and more fundamental insight of what information is removed by the
      multiplicative scatter correction (MSC) method is obtained. It was found that the
      MSC parameters are strongly influenced not only by particle size but also by
      particle concentration as well as refractive index of the medium. The possibility
      of extracting particle size information in addition to particle concentration was
      considered by proposing a two-step method which was tested using a 2-component
      and 4-component data set. This method can in principle, be used in conjunction
      with any scatter correction technique provided that the scatter correction
      parameters exhibit a systematic dependence with respect to particle size and
      concentration. It was found that the approach which uses the MSC parameters gave
      a better estimate of the particle diameter compared to using partial least
      squares (PLS) regression for the 2-component data. For the 4 component data it
      was found that PLS regression gave better results but further examination
      indicated this was due to chance correlations of the particle diameter with the
      two of the absorbing species in the mixture.

PMID- 22975179
TI  - Electroanalytical and isothermal calorimetric study of As(III) complexation by
      the metal poisoning remediators, 2,3-dimercapto-1-propanesulfonate and meso-2,3
      dimercaptosuccinic acid.
AB  - A recently developed methodology, which combines voltammetry, ITC, ESI-MS and
      several chemometric tools, has been applied for the first time to the study of
      As(III) complexes. The ligands considered, DMSA and DMPS, are commonly used to
      treat heavy metal poisoning. The study yields a reliable and consistent picture
      of the binding of As(III) by the chelating therapy agents DMSA and DMPS providing
      an unambiguous description of the stoichiometries of the complexes (ML(2), with
      the occasional appearance of ML in the case of DMSA), both ligands have stability
      constants of the same order, with a logbeta(2) of 9.2 and 9.8, respectively.
      These values confirm the potential efficiency of both ligands in the treatment of
      As(III) poisoning.

PMID- 22975180
TI  - Determination of arsenic and antimony in seawater by voltammetric and
      chronopotentiometric stripping using a vibrated gold microwire electrode.
AB  - The oxidation potentials of As(0)/As(III) and Sb(0)/Sb(III) on the gold electrode
      are very close to each other due to their similar chemistry. Arsenic
      concentration in seawater is low (10-20 nM), Sb occurring at ~0.1 time that of
      As. Methods are shown here for the electroanalytical speciation of inorganic
      arsenic and inorganic antimony in seawater using a solid gold microwire
      electrode. Anodic stripping voltammetry (ASV) and chronopotentiometry (ASC) are
      used at pH <=2 and pH 8, using a vibrating gold microwire electrode. Under
      vibrations, the diffusion layer size at a 5 MUm diameter wire is 0.7 MUm. The
      detection limits for the As(III) and Sb(III) are below 0.1 nM using 2 min and 10
      min deposition times respectively. As(III) and Sb(III) can be determined in
      acidic conditions (after addition of hydrazine) or at neutral pH. In the latter
      case, oxidation of As(0) to As(III) was found to proceed through a transient
      As(III) species. Adsorption of this species on the gold electrode at potentials
      where Sb(III) diffused away is used for selective deposition of As(III). Addition
      of EDTA removes the interfering effect of manganese when analysing As(III).
      Imposition of a desorption step for Sb(III) analysis is required. Total inorganic
      arsenic (iAs=As(V)+As(III)) can be determined without interference from Sb nor
      mono-methyl arsenious acid (MMA) at 1.6<pH<2 using E(dep)=-1 V. Total inorganic
      antimony (iSb=Sb(V)+Sb(III)) is determined at pH 1 using E(dep)=-1.8 V without
      interference by As. The methods were tested in samples from the Irish Sea
      (Liverpool Bay). As(III) was determined on-board ship immediately after sampling.
      As(III) concentrations were found to range from 0.44 to 1.56 nM and were higher
      near the coast. Sb(III) was below the detection limit (<0.1 nM Sb(III)), iAs was
      comprised between 8 and 25 nM while iSb varied from 0.5 to 1.7 nM.

PMID- 22975181
TI  - Functionalized polypyrrole nanotube arrays as electrochemical biosensor for the
      determination of copper ions.
AB  - A novel electrochemical biosensor based on functionalized polypyrrole (PPy)
      nanotube arrays modified with a tripeptide (Gly-Gly-His) proved to be highly
      effective for electrochemical analysis of copper ions (Cu(2+)). The vertically
      oriented PPy nanotube arrays were electropolymerized by using modified zinc oxide
      (ZnO) nanowire arrays as templates which were electrodeposited on indium-tin
      oxide (ITO) coated glass substrates. The electrodes were functionalized by
      appending pyrrole-alpha-carboxylic acid onto the surface of polypyrrole nanotube
      arrays by electrochemical polymerization. The carboxylic groups of the polymer
      were covalently coupled with the amine groups of the tripeptide, and its
      structural features were confirmed by attenuated total reflection infrared (ATR
      IR) spectroscopy. The tripeptide modified PPy nanotube arrays electrode was used
      for the electrochemical analysis of various trace copper ions by square wave
      voltammetry. The electrode was found to be highly sensitive and selective to
      Cu(2+) in the range of 0.1-30 MUM. Furthermore, the developed biosensor exhibited
      a high stability and reproducibility, despite the repeated use of the biosensor
      electrode.

PMID- 22975182
TI  - Simultaneous electrochemical detection of multiple tumor markers based on dual
      catalysis amplification of multi-functionalized onion-like mesoporous graphene
      sheets.
AB  - In this work, a sandwich-type electrochemical immunosensor for simultaneous
      sensitive detection of prostate specific antigen (PSA) and free prostate specific
      antigen (fPSA) is fabricated. Gold nanoparticles (AuNPs) modified Prussian blue
      and nickel hexacyanoferrates nanoparticles were firstly prepared, respectively,
      and then decorated onion-like mesoporous graphene sheets (denoted as Au@PBNPs/O
      GS and Au@NiNPs/O-GS) as distinguishable signal tags to label different detection
      antibodies. Subsequently, streptavidin and biotinylated alkaline phosphatase (bio
      AP) were employed to block the possible remaining active sites. With the
      employment of the as prepared nanohybrids, the dual catalysis amplification can
      be achieved by catalysis of the ascorbic acid 2-phosphate to in situ produce AA
      in the presence of bio-AP, and then AA was further catalyzed by Au@PBNPs/O-GS and
      Au@NiNPs/O-GS nanohybrids, respectively, to obtain the higher signal responses.
      The experiment results show that the linear range of the proposed immunosensor
      for simultaneous determination of fPSA is from 0.02 to 10 ng mL(-1) with a
      detection limit of 6.7 pg mL(-1) and PSA is from 0.01 to 50 ng mL(-1) with a
      detection limit of 3.4 pg mL(-1) (S/N=3). Importantly, the proposed method offers
      promise for rapid, simple and cost-effective analysis of biological samples.

PMID- 22975183
TI  - Novel sample preparation technique with needle-type micro-extraction device for
      volatile organic compounds in indoor air samples.
AB  - A novel needle-type sample preparation device was developed for the effective
      preconcentration of volatile organic compounds (VOCs) in indoor air before gas
      chromatography-mass spectrometry (GC-MS) analysis. To develop a device for
      extracting a wide range of VOCs typically found in indoor air, several types of
      particulate sorbents were tested as the extraction medium in the needle-type
      extraction device. To determine the content of these VOCs, air samples were
      collected for 30min with the packed sorbent(s) in the extraction needle, and the
      extracted VOCs were thermally desorbed in a GC injection port by the direct
      insertion of the needle. A double-bed sorbent consisting of a needle packed with
      divinylbenzene and activated carbon particles exhibited excellent extraction and
      desorption performance and adequate extraction capacity for all the investigated
      VOCs. The results also clearly demonstrated that the proposed sample preparation
      method is a more rapid, simpler extraction/desorption technique than traditional
      sample preparation methods.

PMID- 22975184
TI  - Identification of photodegradation products of Allura Red AC (E129) in a beverage
      by ultra high performance liquid chromatography-quadrupole-time-of-flight mass
      spectrometry.
AB  - The study deals with the identification of the degradation products formed by
      simulated sunlight photoirradiation in a beverage that contains Allura Red AC
      (E129) dye. An UHPLC-MS/MS method that makes use of high resolution quadrupole
      time-of-flight mass spectrometer, was developed. For the identification of the
      degradation products the software tool Information Dependent Acquisition (IDA)
      was used to automatically obtain information about the high resolution MS and
      MS/MS spectra of the species present. Accurate mass data were essential for the
      identification of the appropriate elemental composition: the elucidation of
      unknown chemical structures was obtained by using powerful software to mine the
      recorded chromatogram. The identified degradation products are formed from side
      reactions and/or from the interactions taking place among the dye and other
      ingredients present in the beverage (i.e. ascorbic acid, citric acid, sucrose,
      aromas, strawberry juice and extract of chamomile flowers). The presence of
      aromatic amine or amide groups in the chemical structures of the degradation
      products suggests the potential hazard for the consumer health.

PMID- 22975185
TI  - Visual and trap emission spectrometric detections of Ag (I) ion with mesoporous
      ZnO/CdS@SiO2 core/shell nanocomposites.
AB  - A new method for the preparation of mesoporous ZnO/CdS@SiO(2) core/shell
      nanostructure (CSN) has been developed. The mesoporous silica shells allow Ag(+)
      to enter into the interior of the nanostructures to contact with ZnO/CdS core,
      accordingly causes the quenching of its band edge emission (475 nm) along with a
      simultaneous enhancement of red emission at around 595 nm. So, a novel visual
      fluorescence detection strategy for Ag(+) ion is proposed based on a common
      core/shell Quantum dots nanostructure. Under optimal conditions, the enhanced
      fluorescence intensity at 595 nm increased linearly with the concentration of
      Ag(+) ion ranging from 0.03 MUM to 0.24 MUM with a detection limit (3sigma) of
      3.3 nM.

PMID- 22975186
TI  - Simultaneous trace-levels determination of Hg(II) and Pb(II) ions in various
      samples using a modified carbon paste electrode based on multi-walled carbon
      nanotubes and a new synthesized Schiff base.
AB  - A modified carbon paste electrode based on multi-walled carbon nanotubes (MWCNTs)
      and 3-(4-methoxybenzylideneamino)-2-thioxothiazolodin-4-one as a new synthesized
      Schiff base was constructed for the simultaneous determination of trace amounts
      of Hg(II) and Pb(II) by square wave anodic stripping voltammetry. The modified
      electrode showed an excellent selectivity and stability for Hg(II) and Pb(II)
      determinations and for accelerated electron transfer between the electrode and
      the analytes. The electrochemical properties and applications of the modified
      electrode were studied. Operational parameters such as pH, deposition potential
      and deposition time were optimized for the purpose of determination of traces of
      metal ions at pH 3.0. Under optimal conditions the limits of detection, based on
      three times the background noise, were 9.0*10(-4) and 6.0*10(-4) MUmol L(-1) for
      Hg(II) and Pb(II) with a 90 s preconcentration, respectively. In addition, the
      modified electrode displayed a good reproducibility and selectivity, making it
      suitable for the simultaneous determination of Hg(II) and Pb(II) in real samples
      such as sea water, waste water, tobacco, marine and human teeth samples.

PMID- 22975187
TI  - The sandwich-type electrochemiluminescence immunosensor for alpha-fetoprotein
      based on enrichment by Fe3O4-Au magnetic nano probes and signal amplification by
      CdS-Au composite nanoparticles labeled anti-AFP.
AB  - A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor
      was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of alpha
      fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using
      magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the
      signal tag. The capture probe was prepared by immobilizing the primary antibody
      of AFP (Ab1) on the core/shell Fe(3)O(4)-Au nanoparticles, which was first
      employed to capture AFP antigens to form Fe(3)O(4)-Au/Ab1/AFP complex from the
      serum after incubation. The product can be separated from the background solution
      through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2)
      as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe(3)O(4)-Au/Ab1/AFP
      complex to form a sandwich-type immunocomplex (Fe(3)O(4)-Au/Ab1/AFP/Ab2/CdS-Au),
      which can be further separated by an external magnetic field and produce ECL
      signals at a fixed voltage. The signal was proportional to a certain
      concentration range of AFP for quantification. Thus, an easy-to-use immunosensor
      with magnetic probes and a quantum dots signal tag was obtained. The immunosensor
      performed at a level of high sensitivity and a broad concentration range for AFP
      between 0.0005 and 5.0 ng mL(-1) with a detection limit of 0.2 pg mL(-1). The use
      of magnetic probes was combined with pre-concentration and separation for trace
      levels of tumor markers in the serum. Due to the amplification of the signal tag,
      the immunosensor is highly sensitive, which can offer great promise for rapid,
      simple, selective and cost-effective detection of effective biomonitoring for
      clinical application.

PMID- 22975188
TI  - Novel tandem column method for the rapid isolation of radiostrontium from human
      urine.
AB  - A method has been developed for the isolation of strontium from human urine for
      subsequent determination in sample volumes as low as 5-20 mL. This method
      involves the acidification of the sample using methanesulfonic acid and its
      decolorization using charcoal, treatment of the filtrate with Diphonix((r))
      resin, and subsequent concentration of strontium on Sr resin. Data from retention
      model simulations provided the initial conditions which were then optimized by
      actual column separations. Diphonix((r)) resin was shown to be effective at
      removing alkali metal ions from the urine matrix under conditions that retain
      higher valence ions. The suggested processing method provides 99% recovery of
      Sr(2+), a concentration factor of 50, and an expected per sample processing time
      of less than 1 h.

PMID- 22975189
TI  - Ionic liquids as porogens in the microwave-assisted synthesis of methacrylate
      monoliths for chromatographic application.
AB  - Several imidazolium-based ionic liquids (ILs) with varying cation alkyl chain
      length (C(4)-C(10)) and anion type (tetrafluoroborate ([BF(4)](-)),
      hexafluorophosphate ([PF(6)](-)) and bis(trifluoromethylsulfonyl)imide ([Tf(2)N](
      ))) were used as reaction media in the microwave polymerization of methacrylate
      based stationary phases. Scanning electron micrographs and backpressures of
      poly(butyl methacrylate-ethylene dimethacrylate) (poly(BMA-EDMA)) monoliths
      synthesized in the presence of these ionic liquids demonstrated that porosity and
      permeability decreased when cation alkyl chain length and anion hydrophobicity
      were increased. Performance of these monoliths was assessed for their ability to
      separate parabens by capillary electrochromatography (CEC). Intra-batch precision
      (n=3 columns) for retention time and peak area ranged was 0.80-1.13% and 3.71
      4.58%, respectively. In addition, a good repeatability of RSD(Retention
      time)=<0.30% and ~1.0%, RSD(Peak area)=<1.30% and <4.3%, and
      RSD(Efficiency)=<0.6% and <11.5% for intra-day and inter-day, respectively
      exemplify monolith performance reliability for poly(BMA-EDMA) fabricated using 1
      hexyl-3-methylimidazolium tetrafluoroborate ([C(6)mim][BF(4)]) porogen. This
      monolith was also tested for its potential in nanoLC to separate protein digests
      in gradient mode. ILs as porogens also fabricated different alkyl methacrylate
      (AMA) (C4-C18) monoliths. Furthermore, employing binary IL porogen mixture such
      as 1-butyl-3-methylimidazolium tetrafluoroborate ([C(4)mim][BF(4)]) and 1-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide ([C(4)mim][Tf(2)N])
      successfully decreased the denseness of the monolith, than when using
      [C(4)mim][Tf(2)N] IL alone, enabling a chromatographic run to be performed with
      1:1 ratio produced baseline separation for the analytes. The combination of ILs
      and microwave irradiation made polymer synthesis very fast (~10min), entirely
      green (organic solvent-free) and energy saving process.

PMID- 22975190
TI  - Memory signals from the thalamus: early thalamocortical phase synchronization
      entrains gamma oscillations during long-term memory retrieval.
AB  - The thalamus is believed to be a key node in human memory networks, however, very
      little is known about its real-time functional role. Here we examined the
      dynamics of thalamocortical communication during long-term episodic memory
      retrieval in two experiments. In experiment 1, intrathalamic and surface EEG was
      recorded in an epileptic patient implanted with depth electrodes for brain
      stimulation therapy. In a recognition memory test, early (300-500 ms) stimulus
      linked oscillatory synchrony between mediodorsal thalamic and frontal surface
      electrodes at beta frequency (20 Hz) was enhanced for correctly remembered old
      compared to correctly rejected new items. Directionality measures (Granger
      causality) indicated that the thalamus was the sender, and the neocortex the
      receiver, of this beta signal, which also modulated the power of neocortical
      gamma (55-80 Hz) oscillations (cross-frequency coupling). Experiment 2 validated
      the cross-frequency coupling effects in a healthy participant sample. Confirming
      the findings from experiment 1, significantly increased cross-frequency coupling
      was found over frontal scalp electrodes during successful recognition. Extending
      anatomical knowledge on thalamic connectivity with frontal neocortex, these
      results suggest that the thalamus sends an early memory signal to frontal
      regions, triggering further memory search processes.

PMID- 22975191
TI  - The processing of good-fit semantic anomalies: an ERP investigation.
AB  - The failure-to-detect good-fit semantic anomalies is taken as evidence for
      shallow semantic processing, however the cognitive mechanisms involved are not
      well understood. To investigate this we recorded event-related potentials (ERPs)
      to sentences that contained good and poor-fit semantic anomalies and non
      anomalous controls. Detected good-fit anomalies elicited an N400 effect when
      detection accuracy was stressed, indicating the registration of the anomaly. ERP
      analyses further ruled out that anomaly non-/detection is due to differences in
      initial word encoding or in processing prior contextual information. In addition,
      starting in the P2 interval, the ERP waveform was less positive for non-detected
      than detected anomalies and non-anomalous controls, presumably reflecting a
      language-driven modulation of visual input processing. And finally, detection of
      good-fit anomalies may also depend on the integration of sentential information
      into the discourse model at the end of the critical sentence. Overall, present
      findings support the shallow processing account of anomaly detection failure.

PMID- 22975192
TI  - The temporal dynamics of inflected word recognition: a masked ERP priming study
      of French verbs.
AB  - Morphological aspects of human language processing have been suggested by some to
      be reducible to the combination of orthographic and semantic effects, while
      others propose that morphological structure is represented separately from
      semantics and orthography and involves distinct neuro-cognitive processing
      mechanisms. Here we used event-related brain potentials (ERPs) to investigate
      semantic, morphological and formal (orthographic) processing conjointly in a
      masked priming paradigm. We directly compared morphological to both semantic and
      formal/orthographic priming (shared letters) on verbs. Masked priming was used to
      reduce strategic effects related to prime perception and to suppress semantic
      priming effects. The three types of priming led to distinct ERP and behavioral
      patterns: semantic priming was not found, while formal and morphological priming
      resulted in diverging ERP patterns. These results are consistent with models of
      lexical processing that make reference to morphological structure. We discuss how
      they fit in with the existing literature and how unresolved issues could be
      addressed in further studies.

PMID- 22975193
TI  - The neural correlates of temporal judgments in the duration bisection task.
AB  - Decision processes related to interval timing are commonly examined using the
      duration bisection procedure-a well-established timekeeping task in which
      participants make judgments about whether a series of "probes" are closer in
      duration to a "short" anchor duration or a "long" anchor duration. The specific
      information used during bisection categorization has been a subject of debate.
      Recent research involving the Contingent Negative Variation (CNV) suggests that
      the "short" anchor duration and a value near the geometric mean (GM) of the short
      and long anchors are among the critical pieces of information used during
      bisection categorization judgements. The present study examined a corollary of
      this claim, that memory comparison and decision-making processes related to the
      temporal judgments are completed prior to probe offset when probe durations are
      perceived to be "long;" testing the hypotheses that (1) response times would be
      significantly longer for "short" relative to "long" categorizations and that (2)
      there would be significant differences in ERPs time-locked to probe offset
      between probes judged to be "short" and "long." Both of these predictions were
      realized in the results, providing strong support for the assertion that a value
      near the GM-likely the point of subjective equality (PSE)-is among the critical
      information used during bisection categorization judgments.

PMID- 22975195
TI  - Performing prototype distortion tasks requires no contribution from the explicit
      memory systems: evidence from amnesic MCI patients in a new experimental
      paradigm.
AB  - Evidence shows that amnesic patients are able to categorize new exemplars drawn
      from the same prototype as in previously encountered items. It is still unclear,
      however, whether this ability is due to a spared implicit learning system or
      residual explicit memory and/or working memory resources. In this study, we used
      a new paradigm devised expressly to rule out any possible contribution of
      episodic and working memory in performing a prototype distortion task. We
      enrolled patients with amnesic MCI and Normal Controls. Our paradigm consisted of
      a study phase and a test phase; two-thirds of the participants performed the
      study phase and all participants performed the test phase. In the study phase,
      participants had to judge how pleasant morphed faces, drawn from a single
      prototype, seemed to them. Half of the participants were shown faces drawn from
      the A-prototype and half from the B-prototype. A- and B-faces were opposite in a
      morphing space with a neutral human face at the center. In the test phase,
      participants had to judge the regularity of faces they had never seen before.
      Three different types of faces were shown in the test phase, that is, A-, B-, or
      neutral-faces. We expected that implicit learning of the category boundaries
      would lead to a category-specific increase in perceived regularity. The results
      confirmed our predictions. In fact, trained subjects (compared with subjects who
      did not undergo the study phase) assigned higher regularity scores to new faces
      drawn from the same prototype as the faces seen during training, and they gave
      lower regularity scores to new faces drawn from the opposite prototype. This
      effect was super imposable across subjects' groups.

PMID- 22975194
TI  - Evaluative vs. trait representation in intergroup social judgments: distinct
      roles of anterior temporal lobe and prefrontal cortex.
AB  - When interacting with someone from another social group, one's responses may be
      influenced by both stereotypes and evaluations. Given behavioral results
      suggesting that stereotypes and evaluative associations operate independently, we
      used fMRI to test whether these biases are mediated by distinct brain systems.
      White participants viewed pairs of Black or White faces and judged them based on
      an evaluation (who would you befriend?) or a stereotype-relevant trait (who is
      more likely to enjoy athletic activities?). Multi-voxel pattern analysis revealed
      that a predominantly occipital network represented race in a context-invariant
      manner. However, lateral orbitofrontal cortex preferentially represented race
      during friendship judgments, whereas anterior medial prefrontal cortex
      preferentially represented race during trait judgments. Furthermore,
      representation of race in left temporal pole correlated with a behavioral measure
      of evaluative bias during friendship judgments and, independently, a measure of
      stereotyping during trait judgments. Whereas early sensory regions represent race
      in an apparently invariant manner, representations in higher-level regions are
      multi-componential and context-dependent.

PMID- 22975196
TI  - Counterfactuals in action: an fMRI study of counterfactual sentences describing
      physical effort.
AB  - Counterfactual statements such as if Mary had cleaned the room, she would have
      moved the sofa convey both actual and hypothetical actions, namely, that Mary did
      not clean the room or move the sofa, but she would have done so in some possible
      past situation. Such statements are ubiquitous in daily life and are involved in
      critical cognitive activities like decision-making and evaluation of alternative
      outcomes. Here, we investigate the brain mechanisms and the nature of the
      semantic representations involved in understanding the complex meaning of
      counterfactual statements. We used fMRI to examine brain responses to
      counterfactual statements describing actions of high and low physical effort and
      compared them to similar factual statements describing the same actions. Results
      indicated that the inferior parietal lobule, known to support planning of object
      directed actions, responded more strongly to high-effort than low-effort
      statements. Moreover, counterfactual statements, compared to factual ones,
      recruited a distinctive neural network partially overlapping with action
      execution networks. This network included medial pre-motor and pre-frontal
      structures, which underpin selection and inhibition of alternative action
      representations, and parahippocampal and temporal regions, involved in retrieving
      episodic memories. We argue that counterfactual comprehension recruit action
      related networks encoding and managing alternative representations of behaviors.

PMID- 22975198
TI  - Withdrawing interferon-alpha from psychiatric patients: clinical care or
      unjustifiable stigma?
AB  - IFN-alpha is an effective therapy for chronic viral hepatitis C and today still
      represents an effective first-line treatment. Unfortunately, its use is
      associated with a number of side-effects, including psychiatric problems like
      depression, mania, psychosis, delirium and other cognitive disturbances.
      Clinicians have been concerned about the risks of worsening of pre-existent
      psychiatric disorders and of precipitating suicidal attempts in psychiatric
      patients. The presence of a mental illness is, therefore, often deemed to be a
      contraindication to the use of antiviral treatment. However, this amounts to
      stigmatization and discrimination, as it basically implies withholding a life
      saving medical treatment because of a psychiatric diagnosis. Is this clinically
      and socially acceptable? With novel treatments now entering clinical practice as
      adjuvant to IFN-alpha, it is particularly important to make a statement now, to
      ensure that psychiatric patients are not left behind. The aim of this editorial
      is to critically discuss this notion, by reviewing the few studies (n = 14) that
      have indeed administered IFN-alpha to patients with a pre-existing psychiatric
      disorder. We find evidence that these patients have rates of treatment adherence
      and sustained virological response similar to those of non-psychiatric patients,
      and that their IFN-alpha-induced psychiatric symptoms respond successfully to
      clinical management. We conclude that there is no support to withdrawing IFN
      alpha therapy from psychiatric patients.

PMID- 22975199
TI  - Reproducibility of serum 25-hydroxyvitamin d and vitamin D-binding protein levels
      over time in a prospective cohort study of black and white adults.
AB  - Prospective epidemiologic studies generally rely on 1 baseline biologic sample
      from participants for measurement of prediagnostic biomarkers, assuming that 1
      measurement adequately represents the participant's "typical" level. The body of
      work assessing the reproducibility of circulating serum 25-hydroxyvitamin D
      (25(OH)D) levels over time focuses almost exclusively on populations of European
      descent, and data for vitamin D-binding protein (VDBP) are virtually nonexistent.
      Thus, the authors measured levels of serum 25(OH)D and VDBP twice in samples
      collected between 2005 and 2008 from 225 participants (155 black, 70 white) in
      the Southern Community Cohort Study. Reproducibility for 25(OH)D was uniformly
      high, with adjusted intraclass correlation coefficients (ICCs) of 0.84 (95%
      confidence interval (CI): 0.79, 0.88) for blacks and 0.92 (95% CI: 0.87, 0.95)
      for whites, and there was substantial agreement for assignment of 25(OH)D
      quartile (kappa = 0.83, 95% CI: 0.78, 0.87) and vitamin D adequacy status (kappa
      = 0.76, 95% CI: 0.69, 0.83). VDBP levels were highly stable over time, with
      adjusted ICCs of 0.97 (95% CI: 0.96, 0.98) for blacks and 0.96 (95% CI: 0.93,
      0.97) for whites. These findings suggest that single, baseline 25(OH)D and VDBP
      serum measurements provide reasonably representative measures of these compounds
      for both white and black adults, demonstrating their utility as epidemiologic
      biomarkers in prospective studies.

PMID- 22975197
TI  - The cerebellum as a target for estrogen action.
AB  - This review focuses on the effects of estrogens upon the cerebellum, a brain
      region long ignored as a site of estrogen action. Highlighted are the diverse
      effects of estradiol within the cerebellum, emphasizing the importance of
      estradiol signaling in cerebellar development, modulation of synaptic
      neurotransmission in the adult, and the potential influence of estrogens on
      various health and disease states. We also provide new data, consistent with
      previous studies, in which locally synthesized estradiol modulates cerebellar
      glutamatergic neurotransmission, providing one underlying mechanism by which the
      actions of estradiol can affect this brain region.

PMID- 22975201
TI  - Time-dependent, reversible, oxaborole inhibition of Escherichia coli leucyl-tRNA
      synthetase measured with a continuous fluorescence assay.
AB  - Enzyme assays for the catalytic activity of aminoacyl-tRNA synthetases generally
      measure the incorporation of radioactive amino acids into tRNA. Such assays are
      necessarily discontinuous. Leucyl-tRNA synthetase has recently gained attention
      as the target of novel antimicrobial compounds based on the oxaborole scaffold,
      examples of which have been shown to have slow binding and dissociation kinetics.
      Investigations of the kinetics of inhibition by these compounds would be
      facilitated by a continuous assay of leucyl-tRNA synthetase catalysis. Here we
      report a continuous fluorescence intensity-based assay for leucyl-tRNA synthetase
      in which the pyrophosphate product is converted to phosphate, which is detected
      with nanomolar sensitivity by a phosphate sensor protein. This assay was used to
      measure the time constants for the slow onset of inhibition and long residence
      time of an oxaborole-based inhibitor.

PMID- 22975200
TI  - Continuous monitoring of enzymatic activity within native electrophoresis gels:
      application to mitochondrial oxidative phosphorylation complexes.
AB  - Native gel electrophoresis allows the separation of very small amounts of protein
      complexes while retaining aspects of their activity. In-gel enzymatic assays are
      usually performed by using reaction-dependent deposition of chromophores or light
      scattering precipitates quantified at fixed time points after gel removal and
      fixation, limiting the ability to analyze the enzyme reaction kinetics. Herein,
      we describe a custom reaction chamber with reaction medium recirculation and
      filtering and an imaging system that permits the continuous monitoring of in-gel
      enzymatic activity even in the presence of turbidity. Images were continuously
      collected using time-lapse high-resolution digital imaging, and processing
      routines were developed to obtain kinetic traces of the in-gel activities and
      analyze reaction time courses. This system also permitted the evaluation of
      enzymatic activity topology within the protein bands of the gel. This approach
      was used to analyze the reaction kinetics of two mitochondrial complexes in
      native gels. Complex IV kinetics showed a short initial linear phase in which
      catalytic rates could be calculated, whereas Complex V activity revealed a
      significant lag phase followed by two linear phases. The utility of monitoring
      the entire kinetic behavior of these reactions in native gels, as well as the
      general application of this approach, is discussed.

PMID- 22975202
TI  - Assembly of highly diverse genes using degenerate oligonucleotides by temperature
      cascade.
AB  - The quality of a nucleotide-based library such as a synthetic antibody library is
      highly dependent on the diversity available. Diversity can be generated using
      degenerate oligonucleotides introduced during gene assembly. Conventional
      approaches to gene assembly are not efficient for oligonucleotides with long
      stretches of degeneracy. We propose an efficient alternative for simultaneous
      introduction of three randomized regions in a synthetic antibody gene via
      temperature cascading. The strategy takes advantage of DNA reannealing kinetics.
      The strategy can be adopted for generating diversity of gene inserts during the
      construction of nucleotide-based libraries.

PMID- 22975203
TI  - Mexican adolescents' experience of menarche and attitudes toward menstruation:
      role of communication between mothers and daughters.
AB  - OBJECTIVES: First, to explore the kind of information that Mexican mothers give
      their daughters about menstruation before their menarche, and to study the impact
      of this communication on how prepared the daughters felt when they experienced
      their menarche. Second, to investigate the influence of the menarcheal experience
      on attitudes toward menstruation. DESIGN: Cross-sectional survey. SETTINGS:
      Sample of adolescents attending 3 different public schools. PARTICIPANTS: 405
      Mexican postmenarcheal adolescents, aged 12-15 years. INTERVENTION: Participants
      answered a questionnaire that had 3 parts: (a) General data, (b) topics related
      to menses that participants had discussed with their mothers prior to menarche,
      and (c) menarcheal experience. They also answered a questionnaire about menstrual
      attitudes. RESULTS: Although most of the participants knew what they should do
      when they experienced their menarche, only 39% stated they had felt prepared to
      start menstruating. Regarding menstrual attitudes, adolescents scored highest on
      Negative Feelings and Secrecy rather than on Positive Feelings. Participants who
      had previously discussed the emotional aspects of menses with their mothers were
      more likely to claim they had felt prepared to start menstruating when they got
      their first period (OR = 3.45). The fact that adolescents felt prepared to start
      menstruating predicted positive attitudes toward menstruation (beta = .19)
      CONCLUSIONS: Discussing the emotional aspects of menses prior to menarche is
      crucial to being prepared for menarche, and to holding positive attitudes toward
      menstruation. Information on biological knowledge and practical aspects of menses
      needs to be supplemented with emotional issues.

PMID- 22975205
TI  - High density lipoprotein is an inappropriate substrate for hepatic lipase in
      postmenopausal women.
AB  - BACKGROUND: HDL antiatherogenic effects would not only depend on its
      concentration but also on its biological quality. Hepatic lipase (HL) action on
      HDL acts in one of the last steps of reverse cholesterol transport.
      Cardiovascular risk increases after menopause, however HDL does not decrease even
      when HL is increased. We evaluated HDL capacity as a substrate of HL in healthy
      postmenopausal women (PMW). METHODS: We studied 20 PMW (51-60 y) and 20
      premenopausal (PreMW) (26-40 y). In fasting serum, lipid-lipoprotein profile and
      HDL composition were assessed. Optimal assay conditions for HDL/HL ex vivo
      incubation were established. Increasing HDL-triglyceride concentrations (0.015 to
      0.20 mmol/l) were incubated with post-heparin plasma obtained from a single
      healthy donor as a source of HL. Free fatty acids were measured and kinetic
      parameters calculated: K(m)(app), inverse to enzyme affinity, and V(max).
      RESULTS: HDL composition in PMW exhibits triglyceride enrichment (p<0.001).
      Kinetic analysis revealed higher K(m)(app) in PMW [130 (40-380) vs 45 (20-91)
      mmol/l, p<0.0001)] correlating directly with HDL-triglycerides (r=0.7, p=0.0001).
      Catalytic efficiency, V(max)/K(m)(app) was reduced when compared to controls
      (p=0.0001). CONCLUSION: Triglyceride-enriched HDL from PMW constitutes a poor
      substrate for HL suggesting that this particle may not exert efficiently its
      antiatherogenic function, regardless of plasma concentration.

PMID- 22975206
TI  - Rapid and sensitive cardiac troponin I immunoassay based on fluorescent
      europium(III)-chelate-dyed nanoparticles.
AB  - BACKGROUND: Cardiac troponins are the preferred and recommended biomarkers of
      myocardial infarction. Unfortunately, most of the current commercial assays do
      not meet the guideline recommendations for sensitivity and low-end precision.
      Therefore, improvements in their analytical performance are still needed.
      METHODS: Cardiac troponin I (cTnI) immunoassay was developed. The assay utilized
      a monoclonal antibody and a F(ab')(2) antibody fragment immobilized onto the
      microtiter wells for capturing, and a monoclonal antibody covalently conjugated
      to fluorescent europium(III)-chelate-dyed nanoparticles for detecting. Following
      a 15-min incubation of the sample and nanoparticle-bioconjugates in the capture
      wells, cTnI was quantified directly from the washed well surface by time-resolved
      fluorometry. RESULTS: The limits of detection and quantification were 0.0020
      MUg/l and 0.012 MUg/l, respectively. The response was linear in the measured
      range of 0.003-9.6 MUg/l. The within-run imprecisions were 9.8, 5.1, 7.7 and
      5.4%, and the total imprecisions were 13.1, 10.4, 9.0 and 8.7% at cTnI levels of
      0.007, 0.051, 0.52 and 2.62 MUg/l, respectively. Plasma recoveries of added cTnI
      were 72-119%. Regression analysis with Innotrac Aio! 2nd generation cTnI assay
      yielded a slope (95% confidence intervals) of 1.197 (1.141 to 1.253) and y
      intercept of 0.216 (-0.128 to 0.561)MUg/l (S(yx) = 2.176 MUg/l, n = 212, r =
      0.945). CONCLUSIONS: The developed immunoassay based on europium(III)-chelate
      dyed nanoparticle label allows rapid and sensitive measurement of cTnI.

PMID- 22975204
TI  - Prediction of cochlear implant performance by genetic mutation: the spiral
      ganglion hypothesis.
AB  - BACKGROUND: Up to 7% of patients with severe-to-profound deafness do not benefit
      from cochlear implantation. Given the high surgical implantation and clinical
      management cost of cochlear implantation (>$1 million lifetime cost), prospective
      identification of the worst performers would reduce unnecessary procedures and
      healthcare costs. Because cochlear implants bypass the membranous labyrinth but
      rely on the spiral ganglion for functionality, we hypothesize that cochlear
      implant (CI) performance is dictated in part by the anatomic location of the
      cochlear pathology that underlies the hearing loss. As a corollary, we
      hypothesize that because genetic testing can identify sites of cochlear
      pathology, it may be useful in predicting CI performance. METHODS: 29 adult CI
      recipients with idiopathic adult-onset severe-to-profound hearing loss were
      studied. DNA samples were subjected to solution-based sequence capture and
      massively parallel sequencing using the OtoSCOPE((r)) platform. The cohort was
      divided into three CI performance groups (good, intermediate, poor) and genetic
      causes of deafness were correlated with audiometric data to determine whether
      there was a gene-specific impact on CI performance. RESULTS: The genetic cause of
      deafness was determined in 3/29 (10%) individuals. The two poor performers
      segregated mutations in TMPRSS3, a gene expressed in the spiral ganglion, while
      the good performer segregated mutations in LOXHD1, a gene expressed in the
      membranous labyrinth. Comprehensive literature review identified other good
      performers with mutations in membranous labyrinth-expressed genes; poor
      performance was associated with spiral ganglion-expressed genes. CONCLUSIONS: Our
      data support the underlying hypothesis that mutations in genes preferentially
      expressed in the spiral ganglion portend poor CI performance while mutations in
      genes expressed in the membranous labyrinth portend good CI performance. Although
      the low mutation rate in known deafness genes in this cohort likely relates to
      the ascertainment characteristics (postlingual hearing loss in adult CI
      recipients), these data suggest that genetic testing should be implemented as
      part of the CI evaluation to test this association prospectively.

PMID- 22975207
TI  - Successful salvage therapy of refractory HIV-related cryptococcal meningitis with
      the combination of liposomal amphotericin B, voriconazole, and recombinant
      interferon-gamma.
AB  - We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and
      9 months, respectively, of standard treatment. Both patients were treated
      successfully with a salvage regimen consisting of the combination of liposomal
      amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant
      interferon gamma-1b (200 MUg thrice weekly). Voriconazole was administered at an
      increased dose (5 mg/kg, twice daily) to overcome interactions with co
      administered ritonavir. In both patients, resolution of clinical signs and
      symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after
      10 weeks of salvage therapy. No major side effects were encountered. At the end
      of treatment, both patients were placed on maintenance therapy with oral
      fluconazole; no recurrence has been observed after 4 years of follow-up.

PMID- 22975208
TI  - Genome wide analysis in a family with sensorineural hearing loss, autism and
      mental retardation.
AB  - Hearing loss is a common congenital anomaly with an incidence of 1 in 1000 live
      births. It has been described together with several other clinical features as
      fortuitous association or commune genetic syndrome. In this study, we
      investigated a consanguineous Tunisian family with moderate to profound
      congenital hearing loss, mental retardation and autistic behaviors. We performed
      a genome wide microarray analysis study using approximately 300,000 SNPs in a
      common set of 7 invidious of this family. We identified regions of suggestive
      linkage with hearing loss on chromosomes 6p12 and 7q34. In addition, we
      identified a deletion on chromosome 8p in the two autistic individuals. This
      report presents an illustration of how consanguinity could increase familial
      clustering of multiple hereditary diseases within the same family. The
      application of next generation sequencing for this family seems to be a good
      strategy for further analysis leading to the identification of candidate genes.

PMID- 22975209
TI  - Reduced folate carrier A80G polymorphism and susceptibility to neural tube
      defects: a meta-analysis.
AB  - The reduced folate carrier (RFC1) plays a crucial role in mediating folate
      delivery into a variety of cells. RFC1 polymorphism (A80G) has been reported to
      be associated with increased risk of neural tube defects (NTDs). However, results
      derived from individually underpowered studies are conflicting. We performed a
      systematic search of MEDLINE and EMBASE databases and carried out a meta-analysis
      on the association between RFC1 polymorphism (A80G) and NTDs risk. Overall, a
      significant correlation between RFC1 A80G polymorphism and NTDs risk was found
      neither in infants nor in maternal (allele contrast in infants: OR(RE)=1.15, 95%
      CI: 0.92-1.45; allele contrast in mothers: OR(RE)=1.24, 95% CI: 0.98-1.56). The
      present meta-analysis failed to support a positive association between RFC1 A80G
      polymorphism and susceptibility to NTDs. It is important to realize, however,
      that socio-economic factors, and gene-environment and gene-gene interactions,
      could have influenced the outcome of our meta-analysis. For this reason, a
      relationship between the A80G polymorphism and NTD risk cannot be entirely
      discounted.

PMID- 22975210
TI  - The genomic structure and the expression profile of the Xenopus laevis
      transthyretin gene.
AB  - Transthyretin (TTR) is a major thyroid hormone-binding protein in the amphibian
      tadpole whose plasma mRNA and protein levels are altered during metamorphosis.
      While the temporal and spatial expression patterns and genomic structure of the
      TTR gene are well studied in higher vertebrates, detailed expression pattern in
      the extrahepatic tissues, the transcriptional regulation, and the genomic
      structure have not yet been identified in amphibians. In this study, we attempted
      to elucidate these mechanisms. Here, we determined the genomic structure of the
      Xenopus laevis TTR gene including 5'-flanking regions, and examined TTR
      expression patterns in several tissues. The TTR gene of X. laevis is composed of
      4 exons and 3 introns, and the nucleotide sequence of intron 1 is not similar to
      that previously reported. This suggests that the TTR gene of X. laevis was
      duplicated and the gene cloned in this study was the other copy of previously
      reported gene. We also found that TTR was primarily transcribed in the liver of
      both tadpoles and adults. In the adult liver, TTR transcripts were more abundant
      in males than females. In higher vertebrates, the expression of TTR is controlled
      by several transcription factors including forkhead box A2 (FoxA2). However, in
      the X. laevis liver, FoxA2 expression patterns were not similar to TTR. We also
      found that exogenous FoxA2 increased the X. laevis TTR promoter-driven luciferase
      activity. These results suggest that, in amphibian, the expression of TTR is
      regulated partially by FoxA2, and that another system may exist to control TTR
      expression.

PMID- 22975211
TI  - Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary
      artery disease.
AB  - PURPOSE: A number of studies reported on associations of single nucleotide
      polymorphisms (SNPs) present in chromosome 9p21 with early-onset coronary artery
      disease (CAD). The present study was then undertaken to perform a meta-analysis
      of all the results published to date. METHODS: All studies of the 9p21
      association with early-onset CAD that were published between 2007 and 2012 were
      retrieved from the PubMed database. RevMan 5.0 software was used to perform meta
      analysis of the data that fulfilled the criteria for our meta-analysis. The
      effect size of four SNPs in the 9p21 region on early-onset CAD risk was assessed
      based on the odds ratios (ORs) with calculation of 95% confidence interval (CI).
      RESULTS: A total of 7123 subjects from 7 case-control studies were genotyped.
      Meta-analysis demonstrated disease association for rs2383207 (OR=0.79, 95% CI
      0.71-0.88, P<0.0001), rs2383206 (OR=1.17, 95% CI 1.10-1.25, P<0.00001),
      rs10757278 (OR=1.28, 95% CI 1.15-1.42, P<0.00001), and rs10757274 (OR=1.17, 95%
      CI 1.08-1.33, P=0.02). CONCLUSION: Genetic variation in the chromosome 9p21
      region may contribute to the etiology of early-onset CAD although their effect
      size is rather small.

PMID- 22975212
TI  - Expression analysis of inhibitor of apoptosis and related caspases in the midgut
      and silk gland of the greater wax moth, Galleria mellonella, during metamorphosis
      and under starvation.
AB  - We cloned a cDNA encoding inhibitor of apoptosis (IAP) from the greater wax moth,
      Galleria mellonella. The deduced amino acid sequence showed that GmIAP contains
      two baculoviral IAP repeat (BIR) motifs, followed by a RING finger. The sequence
      comparison showed that GmIAP had high homology to lepidopteran IAPs and
      baculoviral IAPs, as well as dipteran IAPs. GmIAP transcript and its protein
      appeared in both the midgut and the silk gland during metamorphosis and
      starvation where cell death was detected by TUNEL test. IAP, and capases-1, -3, 
      4 and -6 appeared as at least two peaks in the midgut and silk gland during
      metamorphosis. Caspase-1 transcript appeared at the highest level among caspases,
      while caspase-3 and caspase-6 seemed to be the most relevant caspases to IAP
      during metamorphosis suggesting that IAP and caspases may be involved in a core
      apoptosis pathway in the wax moth as in flies and mosquitoes.

PMID- 22975213
TI  - Cabazitaxel in patients with advanced solid tumours: results of a Phase I and
      pharmacokinetic study.
AB  - BACKGROUND: Although the taxanes paclitaxel and docetaxel are among the most
      active agents for the treatment of a wide range of cancers, tumours often develop
      resistance to these treatments. Cabazitaxel is a novel taxane active in both
      preclinical models of chemotherapy-sensitive and -resistant human tumours and
      patients with advanced prostate cancer that progressed following docetaxel
      treatment. AIM: To establish the maximum tolerated dose (MTD) and dose-limiting
      toxicities (DLTs) of cabazitaxel. PATIENTS AND METHODS: Cabazitaxel was
      administered every 3 weeks to patients with advanced solid tumours. The design
      allowed intrapatient dose escalation. The primary objective was to determine the
      MTD. Secondary objectives were to describe the safety profile, establish an
      appropriate dose, determine the pharmacokinetic (PK) profile of cabazitaxel, and
      assess antitumour activity. RESULTS: Twenty-one patients were recruited. The MTD
      was reached at 30 mg/m(2), at which three of five patients experienced
      haematologic DLTs during the first cycle. DLTs during subsequent cycles were
      mainly haematologic and reported at 25 and 30 mg/m(2) dosing levels. Nail
      disorders and severe alopecia were not reported, and neurotoxicity, fluid
      retention and hypersensitivity were mild and infrequent. Cabazitaxel demonstrated
      linear PK, a triphasic elimination profile, with a long half-life and high
      clearance. Of the 19 patients evaluable for response, one unconfirmed partial
      response and six occurrences of stable disease were reported. CONCLUSIONS: The
      25mg/m(2) dose of cabazitaxel was recommended for use in future clinical studies.
      In this study, cabazitaxel had an acceptable tolerability profile and activity in
      cervical, colorectal, endometrial and lung cancers.

PMID- 22975214
TI  - Assessment of the Memorial Sloan-Kettering Cancer Center nomogram to predict
      sentinel lymph node metastases in a Dutch breast cancer population.
AB  - AIM: Sentinel lymph node (SLN) biopsy is an accepted alternative to axillary
      lymph node dissection to assess the axillary tumour status in breast cancer
      patients. Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to
      predict the likelihood of SLN metastases in breast cancer patients. Nomogram
      performance was tested on a Dutch population. METHODS: Data of 770 breast cancer
      patients who underwent successful SLN biopsy were collected. SLN metastases were
      present in 222 patients. A receiver operating characteristic (ROC) curve was
      drawn and the area under the curve was calculated to assess the discriminative
      ability of the MSKCC nomogram. A calibration plot was drawn to compare actual
      versus nomogram-predicted probabilities. RESULTS: The area under the ROC curve
      for the predictive nomogram was 0.67 (95% confidence interval 0.63-0.72) as
      compared to 0.75 in the original population. The nomogram was well-calibrated in
      the Dutch population. CONCLUSIONS: In a Dutch population, the MSKCC nomogram
      estimated risk of sentinel node metastases in breast cancer patients well (i.e.
      calibration) with reasonable discrimination (area under ROC curve). Nomogram
      performance on core needle biopsy data has to be evaluated prospectively.

PMID- 22975215
TI  - Prognostic factors in adolescents and young adults (AYA) with high risk soft
      tissue sarcoma (STS) treated by adjuvant chemotherapy: a study based on pooled
      European Organisation for Research and Treatment of Cancer (EORTC) clinical
      trials 62771 and 62931.
AB  - BACKGROUND: We conducted a retrospective study, pooling data from two clinical
      trials in high risk soft tissue sarcoma (STS) patients, with the objective of
      comparing two different age groups: 15-29 years (adolescents and young adults
      (AYA) population) and >= 30 years. The aim was to determine prognostic factors
      for the AYA population. METHODS: Patients selected for analysis were treated in
      two randomised trials of adjuvant chemotherapy in STS (European Organisation for
      Research and Treatment of Cancer (EORTC) 62771 and 62931). A total of 793
      patients were included with a median follow-up (FU) of 8.74 years (AYA
      population: n=161, median FU 9.46 years; patients >= 30 years: n=632, median FU
      8.62 years). Study endpoints were overall survival (OS) and relapse-free survival
      (RFS). The variables of the multivariate analysis were gender, subtype and grade,
      tumour size and localisation (limb versus other), absence or presence of local
      recurrence and treatment (control arm versus adjuvant chemotherapy). RESULTS:
      Patients' characteristics were globally similar with two exceptions, histological
      subtype (p=0.0043) and tumour size (p<.0001). The commonest sarcoma subtype in
      the AYA population was synovial sarcoma (29%), whereas leiomyosarcoma (18%),
      malignant fibrous histiocytoma (MFH, presently being termed undifferentiated
      pleomorphic sarcoma (UPS), 16%) and liposarcoma (15%) were more frequent in
      patients >= 30 years. For OS, independent favourable prognostic factors were low
      grade and small tumour size for both groups; radical resection and MFH or
      liposarcoma subtype were favourable factors for patients >= 30 years only. For
      RFS, favourable prognostic factors were small tumour size and low grade for both
      groups; tumour location in the extremities was a favourable factor for the AYA
      population only, whereas radical resection and adjuvant chemotherapy treatment
      were favourable factors for patients >= 30y ears only. CONCLUSIONS: Significant
      differences could be found concerning prognostic factors between the AYA
      population and older patients. Interestingly, adjuvant chemotherapy was
      associated with improved RFS only in patients >= 30 years. The results may have
      further implications for the treatment of STS patients in different age groups,
      as well as the design of future clinical trials.

PMID- 22975216
TI  - Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose
      interferon alfa-2b (18 months) in melanoma patients without macrometastatic
      nodes: an open-label, randomised, phase 3 European Association for Dermato
      Oncology (EADO) study.
AB  - AIM: Both low-dose interferon (IFN) alfa-2b and pegylated interferon (Peg-IFN)
      alfa-2b have been shown to be superior to observation in the adjuvant treatment
      of melanoma without macrometastatic nodes, but have never been directly compared.
      Peg-IFN facilitates prolongation of treatment, which could provide additional
      benefit. This multicentre, open-label, randomised, phase 3 trial compared
      standard low-dose interferon IFN and prolonged treatment with Peg-IFN. PATIENTS
      AND METHODS: Patients with resected melanoma >=1.5mm thick and without clinically
      detectable node metastases were randomised 1:1 to treatment with IFN 3 MU
      subcutaneously (SC) three times weekly for 18 months or Peg-IFN 100 MUg SC once
      weekly for 36 months. Sentinel lymph node dissection (SLND) was optional. The
      primary endpoint was disease-free survival (DFS). Secondary endpoints included
      distant metastasis-free survival (DMFS), overall survival (OS) and adverse events
      (AEs) grade 3-4. RESULTS: Of 898 patients enrolled, 896 (443 Peg-IFN, 453 IFN)
      were eligible for evaluation (median follow-up 4.7 years). SLND was performed in
      68.2% of patients. There were no statistical differences between the two arms for
      the primary outcome of DFS (hazard ratio [HR] 0.91, 95% confidence interval [CI]
      0.73-1.15) or the secondary outcomes of DMFS (HR 1.02, 95% CI 0.80-1.32) and OS
      (HR 1.09, 95% CI 0.82-1.45). Peg-IFN was associated with higher rates of grade 3
      4 AEs (47.3% versus 25.2%; p<0.0001) and discontinuations (54.3% versus 30.4%)
      compared with IFN. CONCLUSION: This trial did not show superiority for adjuvant
      Peg-IFN over conventional low-dose IFN in melanoma patients without clinically
      detectable nodes. ClinicalTrials.gov identifier: NCT00221702.

PMID- 22975218
TI  - Superiority of denosumab to zoledronic acid for prevention of skeletal-related
      events: a combined analysis of 3 pivotal, randomised, phase 3 trials.
AB  - BACKGROUND: Patients with bone metastases from advanced cancer often experience
      skeletal-related events (SRE), which cause substantial pain and morbidity.
      Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL),
      is a novel bone-targeted agent with a distinct mechanism of action relative to
      the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned
      analysis evaluates the efficacy and safety of denosumab versus zoledronic acid
      across three pivotal studies. METHODS: Patient-level data from three identically
      designed, randomised, double-blind, active-controlled, phase 3 trials of patients
      with breast cancer, prostate cancer, other solid tumours or multiple myeloma were
      combined. End-points included time to first SRE, time to first and subsequent
      (multiple) SRE, adverse events, time to disease progression and overall survival.
      FINDINGS: Denosumab was superior to zoledronic acid in delaying time to first on
      study SRE by a median 8.21months, reducing the risk of a first SRE by 17% (hazard
      ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P<0.001). Efficacy was
      demonstrated for first and multiple events and across patient subgroups (prior
      SRE status; age). Disease progression and overall survival were similar between
      the treatments. In contrast to zoledronic acid, denosumab did not require
      monitoring or dose modification/withholding based on renal status, and was not
      associated with acute-phase reactions. Hypocalcaemia was more common for
      denosumab. Osteonecrosis of the jaw occurred at a similar rate (P=0.13).
      CONCLUSION: Denosumab was superior to zoledronic acid in preventing SRE with
      favourable safety and convenience in patients with bone metastases from advanced
      cancer.

PMID- 22975220
TI  - What is the evidence for heterozygote advantage selection?
AB  - Recent genomic data have found that many genes show the signal of selection. How
      many of these genes are undergoing heterozygote advantage selection is only
      beginning to be known. Initial genomic surveys have suggested that only a small
      proportion of loci have polymorphisms maintained by heterozygote advantage and
      this is consistent with the few examples generated from other approaches within
      given species. Unless further studies provide large numbers of loci with
      heterozygote advantage, it appears that loci with heterozygote advantage must be
      considered only a small minority of all loci in a species. This is not to say
      that some heterozygote advantage loci do not have important adaptive functions,
      but that their role in overall evolutionary change might be more of an unusual
      phenomenon than a major player in adaptation.

PMID- 22975219
TI  - The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide
      polymorphism (SNP) is associated with promoter methylation and longer survival in
      glioblastoma patients.
AB  - Clinical studies in patients with newly diagnosed glioblastoma treated with
      temozolomide have shown that the methylation status of the O(6)-methylguanine-DNA
      methyltransferase (MGMT) gene is both predictive and prognostic of outcome.
      Methylation of the promoter region of MGMT is the most clinically relevant
      measure of MGMT expression and its assessment has become integral in current and
      planned clinical trials in glioblastoma. Our study confirmed that MGMT
      methylation, assessed by pyrosequencing, is associated with a significant
      survival benefit in glioblastoma patients treated with temozolomide (either
      concurrently with radiotherapy or sequential treatment). More interestingly, our
      study demonstrated that a promoter variant, the c.-56C>T (rs16906252) single
      nucleotide polymorphism (SNP) located within a cis-acting enhancer element at the
      proximal end of MGMT, is associated with the presence of MGMT promoter
      methylation in de novo glioblastoma. Furthermore, we show that the overall
      survival of patients carrying both the SNP and MGMT methylation showed a strong
      survival benefit when compared to either molecular event on their own. Promoter
      reporter experiments in MGMT methylated glioblastoma cell lines showed the T
      allele conferred a ~30% reduction in normalised MGMT promoter activity compared
      to the wild-type haplotype. This might account for the propensity of the T allele
      to undergo promoter methylation, and in turn, the improved survival observed in
      carriers of the T allele. An independent validation on larger cohorts is required
      to confirm the prognostic and predictive value of individuals carrying the T
      allele.

PMID- 22975221
TI  - Persistent infection with neurotropic herpes viruses and cognitive impairment.
AB  - BACKGROUND: Herpes virus infections can cause cognitive impairment during and
      after acute encephalitis. Although chronic, latent/persistent infection is
      considered to be relatively benign, some studies have documented cognitive
      impairment in exposed persons that is untraceable to encephalitis. These studies
      were conducted among schizophrenia (SZ) patients or older community dwellers,
      among whom it is difficult to control for the effects of co-morbid illness and
      medications. To determine whether the associations can be generalized to other
      groups, we examined a large sample of younger control individuals, SZ patients
      and their non-psychotic relatives (n=1852). Method Using multivariate models,
      cognitive performance was evaluated in relation to exposures to herpes simplex
      virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus
      (CMV), controlling for familial and diagnostic status and sociodemographic
      variables, including occupation and educational status. Composite cognitive
      measures were derived from nine cognitive domains using principal components of
      heritability (PCH). Exposure was indexed by antibodies to viral antigens.
      RESULTS: PCH1, the most heritable component of cognitive performance, declines
      with exposure to CMV or HSV-1 regardless of case/relative/control group status (p
      = 1.09 * 10-5 and 0.01 respectively), with stronger association with exposure to
      multiple herpes viruses (beta = -0.25, p = 7.28 * 10-10). There were no
      significant interactions between exposure and group status. CONCLUSIONS:
      Latent/persistent herpes virus infections can be associated with cognitive
      impairments regardless of other health status.

PMID- 22975222
TI  - Differential responses of juvenile and adult South African abalone (Haliotis
      midae Linnaeus) to low and high oxygen levels.
AB  - Marine invertebrates have evolved multiple responses to naturally variable
      environmental oxygen, all aimed at either maintaining cellular oxygen homeostasis
      or limiting cellular damage during or after hypoxic or hyperoxic events. We
      assessed organismal (rates of oxygen consumption and ammonia excretion) and
      cellular (heat shock protein expression, anti-oxidant enzymes) responses of
      juvenile and adult abalone exposed to low (~83% of saturation), intermediate
      (~95% of saturation) and high (~115% of saturation) oxygen levels for one month.
      Using the Comet assay, we measured DNA damage to determine whether the observed
      trends in the protective responses were sufficient to prevent oxidative damage to
      cells. Juveniles were unaffected by moderately hypoxic and hyperoxic conditions.
      Elevated basal rates of superoxide dismutase, glutathione peroxidase and catalase
      were sufficient to prevent DNA fragmentation and protein damage. Adults, with
      their lower basal rate of anti-oxidant enzymes, had increased DNA damage under
      hypoxic and hyperoxic conditions, indicating that the antioxidant enzymes were
      unable to prevent oxidative damage under hypoxic and hyperoxic conditions. The
      apparent insensitivity of juvenile abalone to decreased and increased oxygen
      might be related to their life history and development in algal and diatom
      biofilms where they are exposed to extreme diurnal fluctuations in dissolved
      oxygen levels.

PMID- 22975223
TI  - Oleamide restores sleep in adult rats that were subjected to maternal separation.
AB  - Maternal separation (MS) induces a series of changes in rats' behavior; among
      them a reduction in spontaneous sleep. One potentially impaired system is the
      endocannabinoid system (eCBs), since it contributes to generate sleep. To
      investigate if there are situations early in life that affect the eCBs, which
      would contribute to make rats vulnerable to suffering insomnia, we studied the
      rodent model of MS. Rats were separated from their mothers for 3h-periods daily,
      from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult
      rats), they were implanted with electrodes to record the sleep-waking cycle
      (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following
      groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R),
      OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1
      receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus
      (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in
      both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the
      consequent increase in waking (W) as compared to NMS siblings. OLE normalized the
      SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and
      in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R
      expression and OLE improves sleep in adult rats.

PMID- 22975225
TI  - T-reflex studies in human upper limb muscles during voluntary contraction:
      normative data and diagnostic value for cervical radiculopathy.
AB  - OBJECTIVE: To evaluate the diagnostic utility of the T reflexes elicited from the
      upper limb muscles during standardized volitional contraction monitored by a real
      time integrating electromyographic analyzer. DESIGN: Prospective descriptive
      study. SETTING: Department of orthopedic surgery at a university hospital.
      PARTICIPANTS: Healthy subjects (n=80) evenly distributed across decades of age
      from 21 to 79 years, and 12 consecutive patients with a single cervical root
      lesion based on clinical and magnetic resonance imaging studies and diagnostic
      block. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Using a special
      hammer, which externally triggers the sweep on skin contact, we evoked T reflexes
      in the biceps (C5), brachioradialis (C6), triceps (C7), and the first dorsal
      interosseous muscles (C8). RESULTS: Simultaneous regression analyses yielded
      clinically useful upper limits of normative values for latencies, side-to-side
      differences, and amplitude ratios adjusted to age and arm span. Comparison of the
      T reflexes between the 2 sides localized the solitary root lesions with a high
      sensitivity (92%), specificity (81%), and accuracy (83%). T-reflex studies proved
      helpful to localize the lesion even in patients who solely complained of upper
      limb pain. CONCLUSIONS: The T reflexes with a standardized facilitation of the
      upper limb muscles provide a clinically useful, noninvasive measure to localize
      the C5 to C8 radiculopathies. This study contributes in reassessing the currently
      underused T reflex as an electrodiagnostic technique.

PMID- 22975224
TI  - PON1 status does not influence cholinesterase activity in Egyptian agricultural
      workers exposed to chlorpyrifos.
AB  - Animal studies have shown that paraoxonase 1 (PON1) genotype can influence
      susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However,
      Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related
      toxicity at low exposure conditions in humans. The current study sought to
      determine the influence of PON1 genotype on the activity of blood cholinesterase
      as well as the effect of CPF exposure on serum PON1 in workers occupationally
      exposed to CPF. Saliva, blood and urine were collected from agricultural workers
      (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood
      cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase)
      and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2
      pyridinol (TCPy). The PON1 55 (P<=0.05) but not the PON1 192 genotype had a
      significant effect on CPOase activity. However, both the PON1 55 (P<=0.05) and
      PON1 192 (P<=0.001) genotypes had a significant effect on POase activity. Workers
      had significantly inhibited AChE and BuChE after CPF application; however,
      neither CPOase activity nor POase activity was associated with ChE depression
      when adjusted for CPF exposure (as determined by urinary TCPy levels) and
      stratified by PON1 genotype. CPOase and POase activity were also generally
      unaffected by CPF exposure although there were alterations in activity within
      specific genotype groups. Together, these results suggest that workers retained
      the capacity to detoxify chlorpyrifos-oxon under the exposure conditions
      experienced by this study population regardless of PON1 genotype and activity and
      that effects of CPF exposure on PON1 activity are minimal.

PMID- 22975226
TI  - Changes in blood flow and cellular metabolism at a myofascial trigger point with
      trigger point release (ischemic compression): a proof-of-principle pilot study.
AB  - OBJECTIVE: To demonstrate proof-of-principle measurement for physiologic change
      within an active myofascial trigger point (MTrP) undergoing trigger point release
      (ischemic compression). DESIGN: Interstitial fluid was sampled continuously at a
      trigger point before and after intervention. SETTING: A biomedical research
      clinic at a university hospital. PARTICIPANTS: Subjects (N=2) from a pain clinic
      who had chronic headache pain. INTERVENTIONS: A single microdialysis catheter was
      inserted into an active MTrP of the upper trapezius to allow for continuous
      sampling of interstitial fluid before and after application of trigger point
      therapy by a massage therapist. MAIN OUTCOME MEASURES: Procedural success, pain
      tolerance, feasibility of intervention during sample collection, and
      determination of physiologically relevant values for local blood flow as well as
      glucose and lactate concentrations. RESULTS: Both patients tolerated the
      microdialysis probe insertion into the MTrP and treatment intervention without
      complication. Glucose and lactate concentrations were measured in the physiologic
      range. After intervention, a sustained increase in lactate was noted for both
      subjects. CONCLUSIONS: Identifying physiologic constituents of MTrPs after
      intervention is an important step toward understanding pathophysiology and
      resolution of myofascial pain. The present study forwards that aim by showing
      that proof-of-concept for collection of interstitial fluid from an MTrP before
      and after intervention can be accomplished using microdialysis, thus providing
      methodological insight toward treatment mechanism and pain resolution. Of the
      biomarkers measured in this study, lactate may be the most relevant for detection
      and treatment of abnormalities in the MTrP.

PMID- 22975227
TI  - The value of C4d deposit in post liver transplant liver biopsies.
AB  - BACKGROUND: Presence of C4d in renal and cardiac allografts is a sign of antibody
      mediated rejection and is associated with worse outcomes. The value of C4d in
      liver specimens is controversial. We aimed to determine the association of C4d
      deposition with acute cellular rejection (ACR), hepatitis C (HCV) recurrence, and
      clinical outcome after ABO compatible liver transplants (OLT). METHODS: Using
      immunohistochemical stain, 70 liver biopsies (44 study and 26 control groups)
      were evaluated for C4d deposition. Study group included for-cause post OLT
      biopsies. Staining of endothelial cells was considered positive. RESULTS: In the
      study group C4d was positive in 22.7% versus 3.8% in controls (P=0.03), all had
      portal vein deposits. In 17 biopsies with ACR, 3 had positive C4d (17.6%) versus
      7/27 with HCV recurrence (25.9%) (P=0.4). In HCV recurrence, 3/7 biopsies with
      fibrosing cholestatic hepatitis had positive C4d (42.9%) versus 4/20 without
      these features (20%) (P=0.24). Out of 10 recipients with positive C4d 4 had poor
      outcomes versus 3/22 with negative C4d (P=0.12). CONCLUSIONS: C4d staining was
      significantly more frequent in post OLT biopsies compared with controls. C4d is
      not specifically associated with ACR and does not differentiate it from HCV
      recurrence but is associated with a trend toward poorer outcome.

PMID- 22975228
TI  - Anterior and posterior centers jointly regulate Bombyx embryo body segmentation.
AB  - Insect embryo segmentation is largely divided into long and short germ types. In
      the long germ type, each segment primordium is represented on a large embryonic
      rudiment of the blastoderm, and segmental patterning occurs nearly simultaneously
      in the syncytium. In the short germ type, however, only anterior segments are
      represented in the small embryonic rudiment, usually located on the egg
      posterior, and the rest of the segments are added sequentially from the posterior
      growth zone in a cellular context. The long germ type is thought to have evolved
      from the short germ type. It is proposed that this transition, which appears to
      have occurred multiple times over the course of evolution, was realized through
      the acquisition of a localized anterior instruction center. Here, I examined the
      early segmentation process in the silkmoth Bombyx mori, a lepidopteran insect, in
      which the mechanisms of anterior-posterior (AP) axis formation have not been well
      analyzed. In this insect, both the long germ and short germ features have been
      reported. The mRNAs for two key genes involved in insect AP axis formation,
      orthodenticle (Bm-otd) and caudal (Bm-cad), are localized maternally in the germ
      anlage, where they act as anterior and posterior instruction centers,
      respectively. RNAi studies indicate that, while Bm-cad affects the formation of
      all the even skipped (Bm-eve) stripes, there is also anterior Bm-eve stripe
      formation activity that involves Bm-otd. Thus, there is redundancy in Bm-eve
      stripe formation activity that must be coordinated. Some genetic interactions,
      identified either experimentally or hypothetically, are also introduced, which
      might enable robust AP formation in this organism.

PMID- 22975229
TI  - Maintenance and characterization of multipotent mesenchymal stem cells isolated
      from canine umbilical cord matrix by collagenase digestion.
AB  - Multipotent mesenchymal stem cells have been considered as a novel clinical
      approach for cell therapy and regenerative medicine. In this study, mesenchymal
      stem cells (MSCs) were successfully isolated from canine umbilical cord matrix
      (cUCM; also referred to as Wharton's Jelly) by collagenase digestion and further
      characterized for multipotent properties associated with MSCs. Our cUCM-derived
      MSCs (cUCM-MSCs) were plastic adherent, spindle-shaped and fibroblast-like cells,
      maintaining expression of pluripotency markers such as Oct3/4, Nanog, Sox-2 and
      SSEA-4 as well as normal chromosomal number during a long-term proliferative
      culture. The cells expressed MSCs-specific surface markers, including CD44, CD90,
      CD105, and CD184, but did not CD29, CD33, CD34, and CD45. More importantly, cUCM
      MSCs could differentiate into mesodermal (adipocyte, osteocyte and chondrocyte)
      and ectodermal (neuronal cell) cell lineages. These results imply that
      collagenase digestion would be a highly effective way to isolate multipotent MSCs
      in abundant amounts.

PMID- 22975230
TI  - 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy
      of cardiac rhythm abnormalities: a report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Practice Guidelines.

PMID- 22975231
TI  - The mediating effect of the Mediterranean diet on the role of discretionary and
      hidden salt intake regarding non-fatal acute coronary syndrome or stroke events:
      case/case-control study.
AB  - OBJECTIVES: The aim of the present work was to evaluate the association between
      salt and salty food consumption on the development of an acute coronary syndrome
      (ACS) or ischemic stroke, under the context of adherence to the Mediterranean
      diet. METHODS: During 2009-2010, 1000 participants were enrolled; 250 were
      consecutive patients with a first ACS, 250 were consecutive patients with a first
      ischemic stroke and 500 population-based, control subjects, one-for-one matched
      to the patients by age and sex. Socio-demographic, clinical, psychological,
      dietary and other lifestyle characteristics were measured. Consumption of foods
      with high salt concentration was evaluated with a special score (range 0-10).
      Adherence to the Mediterranean diet was assessed by the validated MedDietScore
      (theoretical range: 0-55). RESULTS: After adjustment for potential confounding
      factors, use of salt added in table was associated with 81% higher likelihood of
      stroke (95% Confidence Interval: 1.03-3.20), whereas no association was observed
      regarding the development of ACS. Salt use during cooking was not associated with
      the development of ACS or stroke. Each unit increase of the score evaluating
      total salty food consumption was associated with 33% higher likelihood of stroke
      development (95% Confidence Interval: 1.08-1.64), but not with ACS. The effect of
      salt and salty food consumption regarding stroke presence was more evident for
      participants with lower adherence to the Mediterranean diet. CONCLUSION: Simple
      dietary changes, with emphasis on reducing salt and salty food consumption, along
      with better adherence to the Mediterranean diet, should be incorporated in public
      health strategies for the primary prevention of stroke.

PMID- 22975232
TI  - Factors affecting sperm recovery rates and survival after centrifugation of
      equine semen.
AB  - Conventional centrifugation protocols result in important sperm losses during
      removal of the supernatant. In this study, the effect of centrifugation force
      (400 or 900 * g), duration (5 or 10 min), and column height (20 or 40 mL;
      Experiment 1); sperm concentration (25, 50, and 100 * 10(6)/mL; Experiment 2),
      and centrifugation medium (EZ-Mixin CST [Animal Reproduction Systems, Chino, CA,
      USA], INRA96 [IMV Technologies, Maple Grove, MN, USA], or VMDZ [Partnar Animal
      Health, Port Huron, MI, USA]; Experiment 3) on sperm recovery and survival after
      centrifugation and cooling and storage were evaluated. Overall, sperm survival
      was not affected by the combination of centrifugation protocol and cooling. Total
      sperm yield was highest after centrifugation for 10 min at 400 * g in 20-mL
      columns (95.6 +/- 5%, mean +/- SD) or 900 * g in 20-mL (99.2 +/- 0.8%) or 40-mL
      (91.4 +/- 4.5%) columns, and at 900 * g for 5 min in 20-mL columns (93.8 +/-
      8.9%; P < 0.0001). Total (TMY) and progressively motile sperm yield followed a
      similar pattern (P < 0.0001). Sperm yields were not significantly different among
      samples centrifuged at various sperm concentrations. However, centrifugation at
      100 * 10(6)/mL resulted in significantly lower total sperm yield (83.8 +/- 10.7%)
      and TMY (81.7 +/- 6.8%) compared with noncentrifuged semen. Centrifugation in
      VMDZ resulted in significantly lower TMY (69.3 +/- 22.6%), progressively motile
      sperm yield (63.5 +/- 18.2%), viable yield (60.9 +/- 36.5%), and survival of
      progressively motile sperm after cooling (21 +/- 10.8%) compared with
      noncentrifuged semen. In conclusion, centrifuging volumes of <= 20 mL minimized
      sperm losses with conventional protocols. With 40-mL columns, it may be
      recommended to increase the centrifugal force to 900 * g for 10 min and dilute
      the semen to a sperm concentration of 25 to 50 * 10(6)/mL in a milk- or
      fractionated milk-based medium. The semen extender VMDZ did not seem well suited
      for centrifugation of equine semen.

PMID- 22975233
TI  - Positional demands of international rugby union: evaluation of player actions and
      movements.
AB  - In rugby union, published analyses of actions and movements of players during
      matches have been limited to small samples of games at regional or national
      level. OBJECTIVES: To analyse movements and activities of players in
      international rugby union matches with a sample size sufficient to clearly
      delineate positional roles. DESIGN: Observational study. METHODS: Actions of 763
      players were coded from video recordings of 90 international matches played by
      the New Zealand national team (the All Blacks) from 2004 to 2010. Movements of
      players were coded for 27 of these matches via a semi-automated player-tracking
      system. Movements and activities of all players from both teams were coded.
      RESULTS: Cluster analysis of activities and time-motion variables produced five
      subgroups of forwards (props, hookers, locks, flankers, Number 8 forwards) and
      five subgroups of backs (scrum-half, fly-half, midfield backs, wings and
      fullbacks). Forwards sustained much higher contact loads per match than backs,
      via scrums, rucks, tackles and mauls. Mean distance covered per match ranged from
      5400 to 6300m, with backs generally running further than forwards. There were
      marked differences between positional groups in the amount of distance covered at
      various speeds. The amount of play per match varies by position due to
      differences in rates at which players are substituted. CONCLUSIONS: The distance
      covered by players at relatively fast running speeds (in excess of 5ms(-1))
      appears to be higher during international matches than when competing at lower
      levels of the professional game. The specific match demands for positional groups
      need to be considered when managing player workloads.

PMID- 22975234
TI  - Characterization of restricted diffusion in uni- and multi-lamellar vesicles
      using short distance iMQCs.
AB  - Improved understanding of the entrapment, transport, and release of drugs and
      small molecules within vesicles is important for drug delivery. Most methods rely
      on contrast agents or probe molecules; here, we propose a new MRI method to
      detect signal from water spins with restricted diffusion. This method is based on
      intermolecular double quantum coherences (iDQCs), which can probe the restricted
      diffusion characteristics at well-defined and tunable microscopic distance
      scales. By using an exceedingly short (and previously inaccessible) distance, the
      iDQC signal arises only from restricted diffusion spins and thereby provides a
      mechanism to directly image vesicle entrapment, transport, and release. Using uni
      and multi-lamellar liposomes and polymersomes, we show how the composition,
      lamellar structure, vesicle size, and concentration affects the iDQC signal
      between coupled water spins at very short separation distances. The iDQC signal
      correlates well with conventional diffusion MRI and a proposed biexponential
      (multicompartmental) diffusion model. Finally, the iDQC signal was used to
      monitor dynamic changes in the lamellar structure as temperature-sensitive
      liposomes released their contents. These short distance iDQCs can probe the
      amount and diffusion of water entrapped in vesicles, which may be useful to
      further understand vesicle properties in materials science and drug delivery
      applications.

PMID- 22975235
TI  - Torque-detected ESR of a tetrairon(III) single molecule magnet.
AB  - Single-crystal studies on anisotropic ESR-active materials can be conveniently
      carried out using torque-detected (TD) ESR, a novel technique which brings to ESR
      the sensitivity typical of torque magnetometry (TM). This method, which is easily
      operated in high magnetic fields and in a wide range of frequencies, was applied
      to investigate magnetic anisotropy in crystals of a tetrairon(III) single
      molecule magnet with an S=5 ground state. TDESR was supported by TM measurements
      carried out in situ and provided an accurate estimate of the second-order axial
      anisotropy parameter D and of the longitudinal fourth-order contribution B(4)(0).
      The results were validated through a parallel angle-resolved investigation by
      traditional high-frequency ESR on the same material.

PMID- 22975236
TI  - Double tuning a single input probe for heteronuclear NMR spectroscopy at low
      field.
AB  - Applications of PASADENA in biomedicine are continuing to emerge due to recent
      demonstrations that hyperpolarized metabolic substrates and the corresponding
      reaction products persist sufficiently long to be detected in vivo. Biomedical
      applications of PASADENA typically differ from their basic science counterparts
      in that the polarization endowed by addition of parahydrogen is usually
      transferred from nascent protons to coupled storage nuclei for subsequent
      detection on a higher field imaging instrument. These pre-imaging preparations
      usually take place at low field, but commercial spectrometers capable of
      heteronuclear pulsed NMR at frequencies in the range of 100 kHz to 1 MHz are
      scarce though, in comparison to single channel consoles in that field regime.
      Reported here is a probe circuit that can be used in conjunction with a phase and
      amplitude modulation scheme we have developed called PANORAMIC (Precession And
      Nutation for Observing Rotations At Multiple Intervals about the Carrier), that
      expands a single channel console capability to double or generally multiple
      resonance with minimal hardware modifications. The demands of this application
      are geared towards uniform preparation, and since the hyperpolarized molecules
      are being detected externally at high field, detection sensitivity is secondary
      to applied field uniformity over a large reaction volume to accommodate
      heterogeneous chemistry of gas molecules at a liquid interface. The probe circuit
      was therefore configured with a large (40 mL) Helmholtz sample coil for
      uniformity, and double-tuned to the Larmor precession frequencies of (13)C/(1)H
      (128/510 kHz) within a custom solenoidal electromagnet at a static field of 12
      mT. Traditional (on-resonant) as well as PANORAMIC NMR signals with signal to
      noise ratios of approximately 75 have been routinely acquired with this probe and
      spectrometer setup from 1024 repetitions on the high frequency channel. The
      proton excitation pulse width was 240 MUs at 6.31 W, compared to a carbon-13
      pulse width of 220 MUs at 2.51 W. When PANORAMIC refocusing waveforms were
      transmitted at a carrier frequency of 319 kHz, integrated signal intensities from
      a spin-echo sequence at both proton (510 kHz) and carbon-13 (128 kHz) frequencies
      were within experimental error to block pulse analogs transmitted on resonance.
      We anticipate that this probe circuit design could be extended to higher and
      lower frequencies, and that when used in conjunction with PANORAMIC phase and
      amplitude modulated arrays, will enable low field imaging consoles to serve as
      multinuclear consoles.

PMID- 22975237
TI  - Chemical shift tensor determination using magnetically oriented microcrystal
      array (MOMA): 13C solid-state CP NMR without MAS.
AB  - Chemical shift tensors for the carboxyl and methyl carbons of L-alanine crystals
      were determined using a magnetically oriented microcrystal array (MOMA) prepared
      from a microcrystalline powder sample of L-alanine. A MOMA is a single-crystal
      like composite in which microcrystals are aligned three-dimensionally in a matrix
      resin. The single-crystal rotation method was applied to the MOMA to determine
      the principal values and axes of the chemical shift tensors. The result showed
      good agreement with the literature data for the single crystal of L-alanine. This
      demonstrates that the present technique is a powerful tool for determining the
      chemical shift tensor of a crystal from a microcrystal powder sample.

PMID- 22975238
TI  - Optimisation of dynamic nuclear polarisation of [1-(13)C] pyruvate by addition of
      gadolinium-based contrast agents.
AB  - Dynamic nuclear polarisation (DNP) of carbon-13 ((13)C) enriched endogenous
      compounds provides a novel means for magnetic resonance imaging and spectroscopy
      of biological processes. Adding small amounts of gadolinium-based contrast agents
      (GBCAs) to the (13)C-enriched substrate matrix increases the amount of
      hyperpolarisation that can be achieved, but also may decrease the longitudinal
      relaxation time (T(1)) of the (13)C nucleus in solution. This study examined the
      effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1
      (13)C]-enriched pyruvic acid. It was found that contrast agents with an open
      chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide)
      caused the largest enhancement (up to 82%) in solid state polarisation relative
      to solutions without GBCA. In the liquid state, T(1) of pyruvate decreased by as
      much as 62% and polarisation was much lower (70%) relative to solutions without
      GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate
      meglumine, Gadoteridol), the solid state polarisation enhancement was only
      slightly less than the open chain GBCA, but enhanced polarisation was retained
      much better in the liquid state with minimal decrease in T(1) (25% at the highest
      GBCA concentrations). Near maximum polarisation in the solid state was obtained
      at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing
      minimal improvement. These results indicate that the macrocyclic contrast agents
      provide the best combination of high solid state and liquid state polarisations
      with minimal loss of T(1) in experiments with hyperpolarised (13)C-enriched
      pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of
      choice for maximising signal in experiments with hyperpolarised (13)C-enriched
      pyruvate, particularly for in vivo measurements where shortened substrate T(1) is
      especially problematic.

PMID- 22975239
TI  - Enhancement of spectral editing efficacy of multiple quantum filters in in vivo
      proton magnetic resonance spectroscopy.
AB  - The performance of multiple quantum filters (MQFs) can be disappointing when the
      background signal also arises from coupled spins. Moreover, at 3.0 T and even
      higher fields the majority of the spin systems of key brain metabolites fall into
      the strong-coupling regime. In this manuscript we address comprehensively, the
      importance of the phase of the multiple quantum coherence-generating pulse (MQ
      pulse) in the design of MQFs, using both product operator and numerical analysis,
      in both zero and double quantum filter designs. The theoretical analyses were
      experimentally validated with the examples of myo-inositol editing and the
      separation of glutamate from glutamine. The results demonstrate that the phase of
      the MQ-pulse per se provides an additional spectral discrimination mechanism
      based on the degree of coupling beyond the conventional level-of-coherence
      approach of MQFs. To obtain the best spectral discrimination of strongly-coupled
      spin systems, therefore, the phase of the MQ-pulse must be included in the
      portfolio of the sequence parameters to be optimized.

PMID- 22975240
TI  - DEER-Stitch: combining three- and four-pulse DEER measurements for high
      sensitivity, deadtime free data.
AB  - Over approximately the last 15 years the electron paramagnetic resonance (EPR)
      technique of double electron electron resonance (DEER) has attracted considerable
      attention since it allows for the precise measurement of the dipole-dipole
      coupling between radicals and thus can lead to distance information between pairs
      of radicals separated by up to ca. 8 nm. The "deadtime free" 4-pulse DEER
      sequence is widely used but can suffer from poor sensitivity if the electron spin
      echo decays too quickly to allow collection of a sufficiently long time trace. In
      this paper we present a method which takes advantage of the much greater
      sensitivity that the 3-pulse sequence offers over the 4-pulse sequence since the
      measured electron spin-echo intensity (for equal sequence lengths) is greater. By
      combining 3- and 4-pulse DEER time traces using a method coined DEER-Stitch
      (DEERS) accurate dipole-dipole coupling measurements can be made which combine
      the sensitivity of the 3-pulse DEER sequence with the deadtime free advantage of
      the 4-pulse DEER sequence. To develop the DEER-Stitch method three systems were
      measured: a semi-rigid bis-nitroxide labeled nanowire, the bis-nitroxide labeled
      protein CD55 with a distance between labels of almost 8 nm and a dimeric copper
      amine oxidase from Arthrobacter globiformis (AGAO).

PMID- 22975241
TI  - Slice-selective broadband refocusing pulses for the robust generation of crushed
      spin-echoes.
AB  - A major challenge for in vivo magnetic resonance spectroscopy with point-resolved
      spectroscopy (PRESS) is the low signal intensity for the measurement of weakly
      scalar coupled spins, for example lactate. The chemical-shift displacement error
      between the two coupling partners of the lactate molecule leads to a signal
      decrease. The chemical-shift displacement error is decreased and therefore the
      lactate signal is increased by using refocusing pulses with a broad bandwidth.
      Previously, slice-selective broadband universal rotation pulses (S-BURBOP) were
      designed and applied as refocusing pulses in the PRESS pulse sequence (Janich MA,
      et al., Journal of Magnetic Resonance, 2011, 213, 126-135). However, S-BURBOP
      pulses leave a phase error across the slice which is superimposed on the spectra
      when spatially resolving the PRESS voxel. In the present novel design of slice
      selective broadband refocusing pulses (S-BREBOP) this phase error is avoided. S
      BREBOP pulses obtain 2.5 times the bandwidth of conventional Shinnar-Le Roux
      pulses and are robust against +/-20% miscalibration of the B(1) amplitude. S
      BREBOP pulses were validated in phantoms and in a low-grade brain tumor of a
      patient. Compared to conventional Shinnar-Le Roux pulses they lead to a decrease
      of the chemical-shift displacement error and consequently a lactate signal
      increase.

PMID- 22975242
TI  - An exact analytical solution for the evolution of a dipole-dipole interacting
      system under spherical diffusion in magnetic resonance experiments.
AB  - A model system consisting of an isotropic ensemble of spin pairs, where dipole
      dipole interaction is assumed to be effective only within each pair, is
      considered. The ideal segment connecting the spins in a couple has a fixed length
      but is free to rotate following a diffusion dynamics. This allows the free
      induction decay (FID) to be derived non-perturbatively by solving the appropriate
      Dyson equation associated to the problem. Motional narrowing can be described
      analytically in terms of only two parameters, i.e. the coupling constant of the
      interaction hamiltonian, b, and the orientational diffusion coefficient D.
      Salient features of the transverse correlation function thus obtained are
      discussed, and a comparison with numerical simulations performed with the
      software SPINEVOLUTION is presented. Interpreting b and D as effective parameters
      describing multiple interactions of a single spin with its neighbors in a real
      system, the analysis of published experimental data on poly(ethyl acrylate) has
      been carried out. It is found that for temperatures higher than and not too close
      to the glass transition, the results are the same as those found within the
      Anderson-Weiss approach by assuming a single time exponential decay of the
      average dipole-dipole interaction. On the other hand, as D tends to zero, FID
      oscillations characteristic of a rigid lattice show up.

PMID- 22975243
TI  - Transfer of the Haupt-hyperpolarization to neighbor spins.
AB  - The NMR hyperpolarization observed for freely rotating methyl groups by exerting
      a temperature jump from 4.2 K to 298 K can be transferred to spins which have a
      spin, spin coupling with the carbon of the methyl group. First, a spin echo
      sequence readjusts the primary up/down signals to an in-phase multiplet. This in
      phase magnetization is then decoupled and transferred by a simple COSY step using
      one scan. The polarization factors at the neighbor spins are about 50 by
      comparing their signal-to-noise ratio with the signal strength after full
      relaxation.

PMID- 22975244
TI  - The world as viewed by and with unpaired electrons.
AB  - Recent advances in electron paramagnetic resonance (EPR) include capabilities for
      applications to areas as diverse as archeology, beer shelf life, biological
      structure, dosimetry, in vivo imaging, molecular magnets, and quantum computing.
      Enabling technologies include multifrequency continuous wave, pulsed, and rapid
      scan EPR. Interpretation is enhanced by increasingly powerful computational
      models.

PMID- 22975245
TI  - Fast Forward Maximum entropy reconstruction of sparsely sampled data.
AB  - We present an analytical algorithm using fast Fourier transformations (FTs) for
      deriving the gradient needed as part of the iterative reconstruction of sparsely
      sampled datasets using the forward maximum entropy reconstruction (FM) procedure
      by Hyberts and Wagner [J. Am. Chem. Soc. 129 (2007) 5108]. The major drawback of
      the original algorithm is that it required one FT and one evaluation of the
      entropy per missing datapoint to establish the gradient. In the present study, we
      demonstrate that the entire gradient may be obtained using only two FT's and one
      evaluation of the entropy derivative, thus achieving impressive time savings
      compared to the original procedure. An example: A 2D dataset with sparse sampling
      of the indirect dimension, with sampling of only 75 out of 512 complex points
      (15% sampling) would lack (512-75)*2=874 points per nu(2) slice. The original FM
      algorithm would require 874 FT's and entropy function evaluations to setup the
      gradient, while the present algorithm is ~450 times faster in this case, since it
      requires only two FT's. This allows reduction of the computational time from
      several hours to less than a minute. Even more impressive time savings may be
      achieved with 2D reconstructions of 3D datasets, where the original algorithm
      required days of CPU time on high-performance computing clusters only require few
      minutes of calculation on regular laptop computers with the new algorithm.

PMID- 22975247
TI  - First determination of the spin relaxation properties of a nitronyl nitroxide in
      solution by electron spin echoes at X-band: a comparison with Tempone.
AB  - We studied by electron spin echo pulse methods the spin relaxation properties of
      a phenyl nitronyl nitroxide radical (2-phenyl-4,4,5,5-tetramethylimidazoline-1
      oxyl 3-oxide, PTIO) at X-band in fluid toluene solution in a wide temperature
      range, and in a water/glycerol 1:1 mixture near room temperature. The relaxation
      properties of PTIO have been compared with that of Tempone, as a widely used
      nitroxide. By a new procedure, based on experimental results on the temperature
      dependences of the relaxation times T(1) and T(2), and on the approximation of an
      isotropic brownian rotational diffusion, we separated non-secular, spin
      rotational and residual terms from the transverse relaxation rate to isolate
      secular and pseudosecular contributions. By comparing the results for the two
      radicals we found the differences in the magnetic properties that give rise to
      slower transverse (T(2)) and longitudinal (T(1)) electron spin relaxation for
      PTIO in the whole temperature range explored in this work.

PMID- 22975246
TI  - A 140 GHz pulsed EPR/212 MHz NMR spectrometer for DNP studies.
AB  - We described a versatile spectrometer designed for the study of dynamic nuclear
      polarization (DNP) at low temperatures and high fields. The instrument functions
      both as an NMR spectrometer operating at 212 MHz ((1)H frequency) with DNP
      capabilities, and as a pulsed-EPR operating at 140 GHz. A coiled TE(011)
      resonator acts as both an NMR coil and microwave resonator, and a double balanced
      ((1)H, (13)C) radio frequency circuit greatly stabilizes the NMR performance. A
      new 140 GHz microwave bridge has also been developed, which utilizes a four-phase
      network and ELDOR channel at 8.75 GHz, that is then multiplied and mixed to
      obtain 140 GHz microwave pulses with an output power of 120 mW. Nutation
      frequencies obtained are as follows: 6 MHz on S=1/2 electron spins, 100 kHz on
      (1)H, and 50 kHz on (13)C. We demonstrate basic EPR, ELDOR, ENDOR, and DNP
      experiments here. Our solid effect DNP results demonstrate an enhancement of 144
      and sensitivity gain of 310 using OX063 trityl at 80 K and an enhancement of 157
      and maximum sensitivity gain of 234 using Gd-DOTA at 20 K, which is significantly
      better performance than previously reported at high fields (>=3 T).

PMID- 22975248
TI  - Relaxation and modulation interference effects in two-pulse electron spin echo
      envelope modulation (ESEEM).
AB  - Two-pulse electron spin echo envelope modulation (ESEEM) line widths are
      influenced by transverse electron spin relaxation, which is in turn induced by
      local field fluctuations. Simultaneous analysis of the decays of the unmodulated
      and modulated parts of the ESEEM signal provides deeper insight into the
      relaxation of a spin system consisting of an electron spin 1/2 coupled to N(I)
      nuclei with spin 1/2. Standard two-pulse ESEEM formulas either do not account for
      relaxation or assume uniform relaxation for all lines. In general, the relaxation
      rates on allowed and forbidden transitions may not be the same. Experimental
      results obtained on a single crystal of Cu(II)-doped L-histidine suggest that
      such a difference exists. Theoretical considerations show that in such a case the
      product rule for two-pulse ESEEM does not extend to expressions including
      relaxation. Product rules in general do not properly account for relaxation in
      three-pulse ESEEM and HYSCORE experiments. Decay of the apparently non
      oscillatory part of the two-pulse echo may be strongly affected by modulation
      interference. Such interference of difference frequencies of matrix nuclei may
      cause a rather flat initial feature, which was previously attributed solely to
      non-exponential phase relaxation of electron spin transitions due to spin
      diffusion of the matrix nuclei. In addition, the sometimes observed drastic
      initial decay of the time domain signal is related to modulation interference of
      multiple-quantum coherences that arise from a strong cross-suppression effect.

PMID- 22975249
TI  - Distance measurements across randomly distributed nitroxide probes from the
      temperature dependence of the electron spin phase memory time at 240 GHz.
AB  - At 8.5 T, the polarization of an ensemble of electron spins is essentially 100%
      at 2 K, and decreases to 30% at 20 K. The strong temperature dependence of the
      electron spin polarization between 2 and 20 K leads to the phenomenon of spin
      bath quenching: temporal fluctuations of the dipolar magnetic fields associated
      with the energy-conserving spin "flip-flop" process are quenched as the
      temperature of the spin bath is lowered to the point of nearly complete spin
      polarization. This work uses pulsed electron paramagnetic resonance (EPR) at 240
      GHz to investigate the effects of spin bath quenching on the phase memory times
      (T(M)) of randomly-distributed ensembles of nitroxide molecules below 20 K at 8.5
      T. For a given electron spin concentration, a characteristic, dipolar flip-flop
      rate (W) is extracted by fitting the temperature dependence of T(M) to a simple
      model of decoherence driven by the spin flip-flop process. In frozen solutions of
      4-Amino-TEMPO, a stable nitroxide radical in a deuterated water-glass, a
      calibration is used to quantify average spin-spin distances as large as r=6.6 nm
      from the dipolar flip-flop rate. For longer distances, nuclear spin fluctuations,
      which are not frozen out, begin to dominate over the electron spin flip-flop
      processes, placing an effective ceiling on this method for nitroxide molecules.
      For a bulk solution with a three-dimensional distribution of nitroxide molecules
      at concentration n, we find W?n?1/r(3), which is consistent with magnetic dipolar
      spin interactions. Alternatively, we observe W?n(32) for nitroxides tethered to a
      quasi two-dimensional surface of large (O~200 nm), unilamellar, lipid vesicles,
      demonstrating that the quantification of spin bath quenching can also be used to
      discern the geometry of molecular assembly or organization.

PMID- 22975250
TI  - Early motor developmental milestones and level of neuroticism in young adulthood:
      a 23-year follow-up study of the Copenhagen Perinatal Cohort.
AB  - BACKGROUND: Studies investigating early developmental factors in relation to
      psychopathology have mainly focused on schizophrenia. The personality dimension
      of neuroticism seems to be a general risk factor for psychopathology, but
      evidence on associations between early developmental precursors and personality
      traits is almost non-existent. This study is therefore the first to investigate
      associations between early motor developmental milestones and neuroticism in
      adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort
      recorded 12 developmental milestones during the child's first year of life. A
      subsample of the cohort comprising 1182 individuals participated in a follow-up
      when they were aged 20-34 years and were administered the Eysenck Personality
      Questionnaire (EPQ). Associations between motor developmental milestones and
      level of neuroticism, extraversion and psychoticism were analysed by multiple
      linear regression adjusting for for sex, single-mother status, parity, mother's
      age, father's age, parental social status and birth weight. RESULTS: Among the
      1182 participants with information on the EPQ, information on milestones was
      available for 968 participants. Infants who developed high levels of neuroticism
      as adults tended to sit without support, crawl, and walk with and without support
      significantly later than individuals with low levels of neuroticism (p values
      <0.05). These results remained significant after adjustment for the included
      covariates and for adult intelligence. CONCLUSIONS: The findings are the first of
      their kind and suggest that delays in early motor development may not only
      characterize psychopathological disorders such as schizophrenia, but may also be
      associated with the personality dimension of neuroticism in adulthood.

PMID- 22975251
TI  - Production of bioethanol from carrot discards.
AB  - A revalorization of discarded carrots as substrate for the production of second
      generation ethanol is proposed. In order to increase the fermentable sugar
      concentration of the musts two strategies were studied: Strategy 1 consisted in
      the enzymatic hydrolysis of bagasse must and Strategy 2 by which carrots were
      milled, dropped into distilled water and hydrolyzed with different enzymes prior
      to compressing and filtering to obtain carrot must. By applying Strategy 2 using
      0.05% (v/v) of the enzyme Optimase CX255 at 70 degrees C and pH 5.5 during 2.5h,
      the fermentable sugars extracted increased 3.5 times. In this way, the production
      of 77.5L of ethanol for each ton of discarded carrots was achieved. This process
      yielded bagasse as byproduct, which could be used for animal feed.

PMID- 22975252
TI  - Bioethanol production: an integrated process of low substrate loading hydrolysis
      high sugars liquid fermentation and solid state fermentation of enzymatic
      hydrolysis residue.
AB  - An integrated process of enzymatic hydrolysis and fermentation was investigated
      for high ethanol production. The combination of enzymatic hydrolysis at low
      substrate loading, liquid fermentation of high sugars concentration and solid
      state fermentation of enzymatic hydrolysis residue was beneficial for conversion
      of steam explosion pretreated corn stover to ethanol. The results suggested that
      low substrate loading hydrolysis caused a high enzymatic hydrolysis yield; the
      liquid fermentation of about 200g/L glucose by Saccharomyces cerevisiae provided
      a high ethanol concentration which could significantly decrease cost of the
      subsequent ethanol distillation. A solid state fermentation of enzymatic
      hydrolysis residue was combined, which was available to enhance ethanol
      production and cellulose-to-ethanol conversion. The results of solid state
      fermentation demonstrated that the solid state fermentation process accompanied
      by simultaneous saccharification and fermentation.

PMID- 22975253
TI  - Abatement of mixture of volatile organic compounds (VOCs) in a catalytic non
      thermal plasma reactor.
AB  - Total oxidation of mixture of dilute volatile organic compounds was carried out
      in a dielectric barrier discharge reactor with various transition metal oxide
      catalysts integrated in-plasma. The experimental results indicated the best
      removal efficiencies in the presence of metal oxide catalysts, especially MnO(x),
      whose activity was further improved with AgO(x) deposition. It was confirmed
      water vapor improves the efficiency of the plasma reactor, probably due to the
      formation of hydroxyl species, whereas, in situ decomposition of ozone on the
      catalyst surface may lead to nascent oxygen. It may be concluded that non-thermal
      plasma approach is beneficial for the removal of mixture of volatile organic
      compounds than individual VOCs, probably due to the formation of reactive
      intermediates like aldehydes, peroxides, etc.

PMID- 22975254
TI  - Supported liquid membrane transport studies on Am(III), Pu(IV), U(VI) and Sr(II)
      using irradiated TODGA.
AB  - Transport behaviour of actinides viz. Am(3+), Pu(4+) and UO(2)(2+) was
      investigated from nitric acid feed conditions using PTFE
      (polytetrafluoroethylene) flat sheet supported liquid membranes (SLM) containing
      an irradiated solvent system comprising of N,N,N',N'-tetra-n-octyldiglycolamide
      (TODGA) as the carrier extractant and N,N-di-n-hexyloctanamide (DHOA) as the
      phase modifier. The present studies were carried out in order to understand the
      effect of irradiation on the long term reusability of the SLM and the
      decontamination behaviour in the absorbed dose range of 0-100 MRad. The studies
      using irradiated carrier included those with irradiated TODGA without any phase
      modifier and with 0.1M as well as 0.5M DHOA as the phase modifier. Transport
      behaviour of all the metal ions were found to be seriously affected with
      increasing radiation dose which was reflected in the decreasing percentage
      transport (%T) as well as permeability co-efficient (P) values. Though Sr(II)
      transport was quite significant with all the three unirradiated solvent systems,
      it was surprisingly low (<5%) when solvents exposed to 100 MRad dose were used in
      the SLM. Separation factors (S.F.) of the actinides over Sr(II) were calculated
      and were found to increase at higher radiation doses suggesting possibility of
      getting better decontamination on prolonged use of the supported liquid membrane
      system.

PMID- 22975255
TI  - Rhizodegradation of petroleum hydrocarbons by Sesbania cannabina in bioaugmented
      soil with free and immobilized consortium.
AB  - The present study reports the effect of bioaugmentation by free and immobilized
      bacterial culture on the rhizodegradation of petroleum-polluted soil using
      Sesbania cannabina plant. Total petroleum hydrocarbon (TPH), hydrocarbon
      degrading bacterial counts, microbial activity and root morphology were assessed
      during 120 days of plant growth. TPH concentration analyzed by GC-MS showed that
      bioaugmentation did not improve the TPH degradation. TPH concentration decreased
      from 2541 mg kg(-1) to 673 mg kg(-1) and 867 mg kg(-1) in the rhizosphere of free
      (FR) and immobilized bacterial inoculated (IR) soil, respectively at the 120th
      day while in the rhizosphere of uninoculated soil (CR) concentration decreased to
      679 mg kg(-1) only at the 90th day, showing higher and rapid rhizodegradation
      with indigenous bacteria than bioaugmented bacterial cultures. Various
      predominant bacterial groups responsible for higher TPH degradation in the
      rhizosphere of S. cannabina were identified by PCR-DGGE analysis. It is concluded
      that natural plant-microbe interaction in the rhizosphere of S. cannabina was
      efficient enough to degrade TPH and plant rhizosphere keeps bacterial community
      in its surrounding therefore immobilized culture had no obvious effect on
      petroleum degradation.

PMID- 22975256
TI  - The investigation of degradation and mineralization of high concentrations of
      formaldehyde in an electro-Fenton process combined with the biodegradation.
AB  - This study was done to evaluate the degradation and mineralization of
      formaldehyde (~ 8000 mg/L) in an electro-Fenton process (EFP) in combination with
      biodegradation. In the first step, the influence of several important parameters
      including solution pH, current density, H(2)O(2) concentration, and reaction time
      were tested on the efficiency of the EFP in degradation and mineralization of
      formaldehyde in a concentrated solution. The optimum pH and current density was
      found to be around 10 and 8.5 mA/cm(2), respectively. The formaldehyde
      degradation in the EFP increased with an increased H(2)O(2) concentration. Under
      optimum pH and current density, the complete degradation and 51% mineralization
      of formaldehyde was attained in the EFP using a H(2)O(2) concentration of
      10mM/min at a short reaction time of 6 min. The biodegradation of the effluent of
      EFP under optimum conditions (complete formaldehyde removal) was also tested. The
      results demonstrated that the concentration of the EFP effluent could be
      efficiently reduced in the bioreactor to below 50mg/L after a biodegradation time
      of 16d. Accordingly, results showed that EFP was a very efficient process for
      degradation and mineralization of a high concentration of formaldehyde so that
      its effluent could be efficiently post-treated with a biological process.

PMID- 22975257
TI  - Cl2 deposition on soil matrices.
AB  - Deposition of chlorine gas, Cl(2), on synthetic soil sample matrices was examined
      in a small chamber to ascertain its potential significance as a chemical sink
      during large-scale releases. The effects of organic matter, clay and sand mass
      fractions of the soil matrix, soil packing, and exposure to ultraviolet (UV)
      light on the observed Cl(2) deposition were examined. Organic matter content was
      found to be the dominant soil variable investigated that affected Cl(2)
      deposition; all other variables exhibited no measurable effect. Analytical
      results from the top 8.5mm of soil columns exposed to Cl(2) were fit to a simple
      kinetic model with six adjustable parameters. The kinetic model included two
      reactive bins to account for fast- and slow-reacting material in the soil
      matrices. The resulting empirical equation agreed with the data to within a
      factor of two and accurately predicted results from soil mixes not used to
      optimize the adjustable parameters. Total Cl(2) deposition, assuming a
      penetration depth of 8.5mm, was calculated to be as high as 160 metric tons per
      square kilometer for soil with an organic content of 10%, and inferred deposition
      velocities were as high as 0.5 cm/s for organically rich soil.

PMID- 22975258
TI  - Degradation of 2,4-dihydroxibenzoic acid by vacuum UV process in aqueous
      solution: kinetic, identification of intermediates and reaction pathway.
AB  - 2,4-Dihydroxybenzoic acid (2,4-DHBA) is found frequently as a pollutant in
      natural waters and represents a threat to water quality because it is a precursor
      to the formation of quinones which are highly toxic. The degradation of 2,4-DHBA
      using the vacuum UV photolysis of water has been investigated. Irradiation was
      carried out in an annular photoreactor equipped with a Xe-excimer lamp situated
      in the centre and emitting at 172 nm. The degradation kinetic followed a pseudo
      first order and the reaction has been found to be very heterogeneous, especially
      at low concentration. Impacts of oxygen or temperature have also been
      investigated but no effect has been shown. LC-MS and HPLC-UV combined with other
      analytical techniques allowed the identification of the formation of
      trihydroxybenzoic acids and trihydroxybenzenes which underwent a ring opening,
      conducting to the formation of aliphatic products named alpha, beta, delta and
      gamma. These products were in turn degraded successively into maleic acid, malic
      and succinic acid, malonic acid, glyoxalic acid and oxalic acid before reaching
      the complete mineralization in about 180 min. The proposed reaction pathway has
      shown to be very different from the one observed for the TiO(2) photocatalysis
      which involves only holes (h(+)) without any formation of aromatic intermediates.
      The different behaviours of 2,4-DHBA towards the h(+) and HO make it a good probe
      to identify involved entities.

PMID- 22975259
TI  - In situ assembly of well-dispersed Au nanoparticles on TiO2/ZnO nanofibers: a
      three-way synergistic heterostructure with enhanced photocatalytic activity.
AB  - The TiO(2)/ZnO nanofibers embedded by Au nanoparticles (TiO(2)/ZnO/Au NFs) were
      fabricated by combining the electrospinning technique (for TiO(2)/ZnO nanofibers)
      and an in situ reduction approach (for Au nanoparticles). X-ray diffraction,
      scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission
      electronmicroscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance
      spectroscopy and photoluminescence spectroscopy, were used to characterize the as
      synthesized nanofibers. The results showed that small Au nanoparticles (Au NPs)
      were well dispersed on the TiO(2)/ZnO nanofibers (TiO(2)/ZnO NFs). And, the
      TiO(2)/ZnO/Au nanofibers showed high charge separation efficiency under
      ultraviolet excitation, as evidenced by photoluminescence spectra. The
      photocatalytic studies revealed that the TiO(2)/ZnO/Au NFs exhibited enhanced
      photocatalytic efficiency of photodegradation of Methyl orange (MO) and 4
      nitrophenol (4-NP) compared with the pure TiO(2) nanofibers, ZnO nanofibers and
      TiO(2)/ZnO NFs under ultraviolet excitation, which might be attributed to the
      high separation efficiency of photogenerated electron-hole pairs based on the
      photosynergistic effect among the three components of TiO(2), ZnO and Au. And,
      the TiO(2)/ZnO/Au NFs could be easily separated and recycled due to their one
      dimensional nanostructural property.

PMID- 22975260
TI  - Recovery of iron from zinc leaching residue by selective reduction roasting with
      carbon.
AB  - The recovery of iron from zinc leaching residue by selective reduction roasting
      with carbon was studied. The effects of roasting temperature, duration time and
      mass ratio of carbon to residue on decomposition of ZnFe(2)O(4), iron recovery
      and iron grade were investigated based on thermodynamic calculation and phase
      composition analysis of zinc leaching residue. 58.6% of iron grade in magnetic
      concentrate and 68.4% of iron recovery were achieved after the residue roasted at
      750 degrees C for 1h under carbon to residue mass ratio of 4%. The phase
      composition of roasted residue indicated that the ZnFe(2)O(4) decomposed in four
      stages: reduction of ZnFe(2)O(4) to ZnO and Fe(3)O(4), reduction of Fe(3)O(4) to
      FeO, formation of Fe(0.85-x)Zn(x)O and reduction of FeO to Fe. A technological
      process for simultaneously recovering iron and zinc from zinc leaching residue is
      proposed.

PMID- 22975261
TI  - Toxicity of inorganic aluminium at spring snowmelt--in-stream bioassays with
      brown trout (Salmo trutta L.).
AB  - Although the acid load has decreased throughout Scandinavia, acidic soils still
      mobilise aluminium (Al) that is harmful to brown trout. We hypothesise that there
      are thresholds for Al toxicity and that the toxicity can be traced from the water
      content to gill accumulation and the consequential physiological effects. During
      snowmelt, yearlings were exposed to a gradient of pH and inorganic monomeric Al
      (Al(i)) in humic streams to study the toxic effects and mortality. Gill Al and
      physiological blood analyses [haemoglobin (Hb), plasma chloride (P-Cl) and
      glucose (Glu)] were measured. As the water quality deteriorated, Al accumulated
      on the gills; Hb and Glu increased; P-Cl decreased, and mortality occurred.
      Moribund fish had significantly increased gill Al and Hb, suggesting that
      respiratory disturbances contributed to mortality. Decreased P-Cl and plasma
      availability indicated an ion regulatory disturbance and possibly circulatory
      collapse. Al(i) should be less than 20 MUg/L, and pH higher than 5.0, to sustain
      healthy brown trout populations. These thresholds can be used to fine-tune lime
      dose, as both Al(i) and pH levels have to be balanced to prevent harm in the
      recovering aquatic biota. Although Al is tightly linked to pH, local variation in
      Al availability in soil and bedrock affects the Al release and subsequent toxic
      Al(i) episodes in some catchment areas.

PMID- 22975262
TI  - Prenatal nicotine exposure induced a hypothalamic-pituitary-adrenal axis
      associated neuroendocrine metabolic programmed alteration in intrauterine growth
      retardation offspring rats.
AB  - Prenatal nicotine exposure inhibits the functional development of the
      hypothalamic-pituitary-adrenal (HPA) axis and alters glucose and lipid metabolism
      in intrauterine growth retardation (IUGR) fetal rats, but the postnatal
      consequence is unknown. We aimed to verify a neuroendocrine metabolic programmed
      alteration in IUGR offspring whose mothers were subcutaneously treated with
      2mg/kgd of nicotine from gestational day 11 to 20. In the nicotine group, blood
      adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were higher
      before postnatal day 35 and then returned to lower than the respective control.
      The adult offspring showed unchanged blood glucose but increased blood total
      cholesterol (TCH) and triglyceride (TG) levels. However, after chronic stress,
      the mRNA expression levels of hippocampal glucocorticoid receptor (GR) and
      mineralocorticoid receptor (MR) were lower, but gain rates of ACTH and CORT
      levels were greater compared to the control. Additionally, the level of blood
      glucose was increased, while the elevated levels of blood TCH and TG before
      stress were close to the control levels. These results suggested that prenatal
      nicotine exposure induced an HPA axis-associated neuroendocrine metabolic
      programmed alteration in adult offspring, which might be attributed to
      hippocampal functional injury in utero.

PMID- 22975263
TI  - Relevance of non-guideline studies for risk assessment: the coverage model based
      on most frequent targets in repeated dose toxicity studies.
AB  - A common challenge for human risk assessment is the quality of the available
      animal studies. Non-guideline studies are often limited for different aspects of
      study design and documentation. Within this publication the relevance of a
      limited scope of examination is discussed. Preliminary analyses of the RepDose
      database have shown that liver, body weight, kidney and clinical symptoms are
      frequently affected in oral repeated dose toxicity in rats and mice (Bitsch et
      al., 2006), while many other targets are seldom affected. As most of these
      targets are investigated frequently also in non-guideline studies, it is likely
      that they provide a reliable NOEL, although the full spectrum of endpoints has
      not been covered. Based on RepDose data we investigate the relevance of
      individual targets for determining the LOEL and the consequences for risk
      assessment. The resulting coverage model for subchronic oral rat studies includes
      up to six targets and an additional assessment factor for LOEL extrapolation. It
      can be applied to assess the reliability of non-guideline studies with respect to
      the scope of examination. Furthermore the application of the coverage model to
      other databases will increase and/or specify the chemical domain and reveal
      respective targets as well as effects.

PMID- 22975264
TI  - Identification and validation of a novel lead compound targeting 4
      diphosphocytidyl-2-C-methylerythritol synthetase (IspD) of mycobacteria.
AB  - Tuberculosis is a serious threat to world-wide public health usually caused in
      humans by Mycobacterium tuberculosis (M. tuberculosis). It exclusively utilizes
      the methylerythritol phosphate (MEP) pathway for biosynthesis of isopentenyl
      diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), the
      precursors of all isoprenoid compounds. The 4-diphosphocytidyl-2-C-methyl-D
      erythritol synthase (IspD; EC 2.7.7.60) is the key enzyme of the MEP pathway. It
      is also of interest as a new chemotherapeutic target, as the enzyme is absent in
      mammals and ispD is an essential gene for growth. A high-throughput screening
      method was therefore developed to identify compounds that inhibit IspD. This
      process was applied to identify a lead compound, domiphen bromide (DMB), that may
      effectively inhibit IspD. The inhibitory action of DMB was confirmed by over
      expressing or down-regulating IspD in Mycobacterium smegmatis (M. smegmatis),
      demonstrating that DMB inhibit M. smegmatis growth additionally through an IspD
      independent pathway. This also led to higher levels of growth inhibition when
      combined with IspD knockdown. This novel IspD inhibitor was also reported to
      exhibit antimycobacterial activity in vitro, an effect that likely occurs as a
      result of perturbation of cell wall biosynthesis.

PMID- 22975265
TI  - Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells
      grown under low-folate conditions.
AB  - Elevated homocysteine is a risk marker for several major human pathologies.
      Emerging evidence suggests that perturbations of folate/homocysteine metabolism
      can directly modify production of inflammatory mediators. Pemetrexed acts by
      inhibiting thymidylate synthetase (TYMS), dihydrofolate reductase (DHFR), and
      glycinamide ribonucleotide formyltransferase (GARFT). EA.hy 926 cells grown under
      low ("Lo") and high ("Hi") folate conditions were treated with pemetrexed. The
      concentrations of several intracellular folate derivatives were measured using LC
      MRM/MS. Lo cells had lower total folate concentrations and a different
      distribution of the intracellular folate derivatives than Hi cells. Treatment
      with pemetrexed caused a decrease in individual folate analytes. Microarray
      analysis showed that several genes were significantly up or down-regulated in
      pemetrexed treated Lo cells. Several of the significantly up-regulated
      transcripts were inflammatory. Changes in transcript levels of selected targets,
      including C3, IL-8, and DHFR, were confirmed by quantitative RT-PCR. C3 and IL-8
      transcript levels were increased in pemetrexed-treated Lo cells relative to Lo
      controls; DHFR transcript levels were decreased. In Lo cells, IL-8 and C3 protein
      concentrations were increased following pemetrexed treatment. Pemetrexed drug
      treatment was shown in this study to have effects that lead to an increase in pro
      inflammatory mediators in Lo cells. No such changes were observed in Hi cells,
      suggesting that pemetrexed could not modify the inflammatory profile in the
      context of cellular folate sufficiency.

PMID- 22975266
TI  - Isolation and characterization of moojenin, an acid-active, anticoagulant
      metalloproteinase from Bothrops moojeni venom.
AB  - A fibrinogenolytic metalloproteinase from Bothrops moojeni venom, named moojenin,
      was purified by a combination of ion-exchange chromatography on DEAE-Sephacel and
      gel filtration on Sephacryl S-300. SDS-PAGE analysis indicated that moojenin
      consists of a single polypeptide chain and has a molecular mass about 45 kDa.
      Sequencing of moojenin by Edman degradation revealed the amino acid sequence
      LGPDIVSPPVCGNELLEVGEECDCGTPENCQNE, which showed strong identity with many other
      snake venom metalloproteinases (SVMPs). The enzyme cleaves the Aalpha-chain of
      fibrinogen first, followed by the Bbeta-chain, and shows no effects on the gamma
      chain. Moojenin showed a coagulant activity on bovine plasma about 3.1 fold lower
      than crude venom. The fibrinogenolytic and coagulant activities of the moojenin
      were abolished by preincubation with EDTA, 1,10-phenanthroline and beta
      mercaptoethanol. Moojenin showed maximum activity at temperatures ranging from 30
      to 40  degrees C and its optimal pH was 4.0. Its activity was completely lost at
      temperatures above 50  degrees C. Moojenin induced necrosis in liver and muscle,
      evidenced by morphological alterations, but did not cause histological
      alterations in mouse lungs, kidney or heart. Moojenin rendered the blood
      uncoagulatable when it was intraperitoneally administered into mice. This
      metalloproteinase may be of medical interest because of its anticoagulant
      activity.

PMID- 22975267
TI  - Isolation, amino acid sequence and biological characterization of an "aspartic
      49" phospholipase A2 from Bothrops (Rhinocerophis) ammodytoides venom.
AB  - A phospholipase enzyme was separated by chromatography from the venom of the
      snake Bothrops (Rhinocerophis) ammodytoides and characterized. The experimentally
      determined molecular weight was 13,853.65 Da, and the full primary structure was
      determined by Edman degradation and mass spectrometry analysis. The enzyme
      contains 122 amino acids residues closely stabilized by 7 disulfide bridges with
      an isoelectric point of 6.13. Sequence comparison with other known secretory PLA2
      shows that the enzyme isolated belongs to the group II, presenting an aspartic
      acid residue at position 48 (numbered by convention as Asp49) of the active site,
      and accordingly displaying enzymatic activity. The enzyme corresponds to 3% of
      the total mass of the venom. The enzyme is mildly toxic to mice. The intravenous
      LD50 of this phospholipase in CD-1 mice was around 6 MUg/g of mouse body weight
      (more exactly 117 MUg/mouse of 20 g) and the minimal mortal dose (MMD) was
      estimated to be close to 10 MUg/g. In contrast, the LD50 of the venom was circa 2
      MUg/g mouse body weight. Toxicological analyses of the purified enzyme were
      performed in vitro and in vivo using experimental animals (mice and rats). The
      enzyme at high doses caused pulmonary congestion, intraperitoneal bleeding,
      inhibition of clot retraction and muscle tissue alterations with increasing of
      creatine kinase levels.

PMID- 22975268
TI  - Sunscreen use in NCAA collegiate athletes: identifying targets for intervention
      and barriers to use.
AB  - OBJECTIVE: Ultraviolet radiation is a known risk factor for skin cancer and
      photoaging. Athletes are at high-risk with frequent sun exposure during peak
      hours of ultraviolet radiation. The aim of this study was to identify attitudes,
      personal characteristics, and barriers associated with sunscreen use among a high
      risk athlete population. METHODS: A cross-sectional survey study conducted in 290
      collegiate athletes from April 2010 to June 2011 at Duke and Stanford
      Universities. RESULTS: The average athlete spent 4h per day and 10 months per
      year training outdoors. While 96% agreed that sunscreen helps prevent skin
      cancer, over 50% never used sunscreen and 75% used sunscreen 3 or fewer
      days/week. Having a coach or athletic administrator discuss photoprotection was
      significantly associated with sunscreen use. Predictors of sunscreen use were
      female gender, sunburns in the last year, belief at risk for skin cancer, knowing
      someone with skin cancer, and being worried about wrinkles, sun burns, or skin
      cancer. CONCLUSION: Continued identification of characteristics and barriers to
      sunscreen use can lead to targeted interventions and education in this high-risk
      group of collegiate athletes with early and elevated total lifetime ultraviolet
      exposure.

PMID- 22975269
TI  - [Ethmoidal mucocele after transpalpebral bony orbital decompression].
AB  - We report a case of a late ethmoidal mucocele occurring after transpalpebral bony
      orbital decompression. A 39-year-old man presented with a recurrence of a right
      sided proptosis without signs of orbital inflammation. The patient had undergone
      bilateral transpalpebral bony orbital decompression for dysthyroid orbitopathy 2
      years prior. Orbital CT scan showed a large mucocele in the supero-lateral right
      ethmoidal sinus with lateral extension to the medial rectus. The patient was
      therefore referred to an ear, nose and throat (ENT) surgeon, who performed an
      anterior ethmoidectomy with marsupialization and drainage of the mucocele via an
      endoscopic approach. A complete postoperative resolution of proptosis was
      observed without recurrence of the mucocele to date, approximately 6 months
      postoperative. Sinus complications occurring after orbital decompression may
      include sinusitis, hematoma, imploding antrum syndrome and mucoceles. Recurrent
      proptosis secondary to an ethmoidal mucocele is a rare event after bony orbital
      decompression surgery, with only two cases reported in the international
      literature. Management requires ophthalmologic diagnosis and collaboration
      between the ophthalmologist and otorhinolaryngologist.

PMID- 22975270
TI  - [Wegener's granulomatosis diagnosed by orbital-meningeal presentation: a case
      report].
AB  - Wegener's granulomatosis is a necrotizing granulomatous vasculitis with a strong
      affinity for the upper respiratory tract, lung and kidney. The ophthalmologic
      manifestation most often presents as inflammatory orbital pseudotumor or
      scleritis. We report a case of a 27-year-old woman with an orbital-meningeal
      presentation leading to a diagnosis of Wegener's granulomatosis.

PMID- 22975271
TI  - [Oculocutaneous albinism].

PMID- 22975272
TI  - [Ligneous conjunctivitis].

PMID- 22975273
TI  - Synthesis of bivalent glycoclusters containing GlcNAc as hexasaccharide mimetics.
      Bactericidal activity against Helicobacter pylori.
AB  - The Cu(I) catalysed cycloaddition reaction of azides and alkynes has been used to
      generate a series of divalent GlcNAc clusters with both alpha and beta
      configurations. These glycoclusters can be considered as potential mimetics of an
      anti Helicobacter pylori hexasaccharide as they present two GlcNAc residues
      grafted onto a core scaffold. Two bivalent compounds based on alpha-O-GlcNAc were
      identified that selectively reduced the viability of H. pylori. These compounds
      showed activity towards different strains of H. pylori (Pu4 vs P12). The activity
      of the oligosaccharide mimetics is speculated to be due to the GlcNAc residues
      being able to adopt spatial arrangements accessible to the anti H. pylori
      hexasaccharide which may be important for activity.

PMID- 22975274
TI  - Convenient syntheses of 1,2-trans selenoglycosides using isoselenuronium salts as
      glycosylselenenyl transfer reagents.
AB  - Se-glycosyl-isoselenuronium salts such as three and four which can be prepared in
      one high-yielding step from acetohalogeno sugars proved to be convenient starting
      materials for the syntheses of a variety of selenoglycosides. Reaction with
      (ar)alkyl halides proceeds under mild conditions, in short time, at room
      temperature to afford the corresponding selenoglycosides in good yields. Aryl
      halides react to appreciable extent only if bearing activating nitro groups on
      the aromatic ring. Reactions with acylating reagents such as acetic anhydride and
      benzoyl chlorides furnished anomeric selenoesters some of which were recently
      proposed as starting compounds for alternative selenoglycoside syntheses.
      Selenodisaccharides with two different monosaccharide units could also be
      prepared via reactions of glycosyl-isoselenuronium salts with monosaccharide
      derivatives bearing primary or secondary triflate groups.

PMID- 22975275
TI  - Production of intracellular heparosan and derived oligosaccharides by lyase
      expression in metabolically engineered E. coli K-12.
AB  - The cluster of genes of capsular K5 heparosan is composed of three regions,
      involved in the synthesis and the exportation of the polysaccharide. The region 2
      possesses all the necessary genes involved in the synthesis of heparosan, namely
      kfiA, encoding alpha-4-N-acetylglucosaminyltransferase, kfiD, encoding beta-3
      glucuronyl transferase, kfiC, encoding UDP-glucose dehydrogenase (UDP-glucuronic
      acid synthesis), and kfiB encoding a protein of unknown function. The cloning and
      expression of kfiADCB into Escherichia coli K-12 were found to be sufficient for
      the production of heparosan, which accumulates in the cells due to a lack of the
      exporting system. The concentration of recombinant heparosan reached one gram per
      liter under fed-batch cultivation. The cytoplasmic localization of heparosan
      inside the bacteria allowed subsequent enzymatic modifications such as a partial
      degradation with K5 lyase when expressed intracellularly. Under these conditions,
      the production of DP 2-10 oligosaccharides occurred intracellularly, at a
      concentration similar to that of recombinant intracellular heparosan.

PMID- 22975276
TI  - Synthesis of 2-fluoro and 4-fluoro galactopyranosyl phosphonate analogues of UDP
      Gal.
AB  - Two novel nonisosteric UDP-Gal analogues, (2-deoxy-2-fluoro- and 4-deoxy-4-fluoro
      alpha-D-galactopyranosyl) phosphonoyl phosphates, were synthesized by optimized
      multistep procedures starting from 3,4,6-tri-O-benzyl-D-galactal and allyl 2,3,6
      tri-O-benzyl-alpha-D-glucopyranoside, respectively. The key steps were a
      Michaelis-Arbuzov reaction of respective deoxy-fluoro-D-galactopyranosyl acetate
      with triethyl phosphite followed by a Moffatt-Khorana coupling reaction with UMP
      morpholidate. The structure of all new compounds was confirmed by NMR and mass
      spectroscopies..

PMID- 22975277
TI  - Stereoselective synthesis of C18-guggultetrol and C18-phytosphingosine analogues
      from D-fructose.
AB  - A series of C(18)-guggultetrol stereo isomers and C(18)-phytosphingosine
      regio/stereo isomers were synthesised in a stereoselective fashion involving
      metal mediated fragmentation, stereoselective reduction, 1,4 O -> O silyl
      migration, and Grubbs' cross metathesis as key steps. d-Fructose was used as a
      raw material for the preparation of all the analogues. The isophytosphingosine
      derivatives were evaluated against their 5-LOX (5-lipoxigenase) inhibitory
      activity.

PMID- 22975278
TI  - Anthraquinone glycosides from Cassia roxburghii and evaluation of its free
      radical scavenging activity.
AB  - The methanolic extract of the leaves of Cassia roxburghii DC., was investigated
      for its anthraquinone glycosides and antioxidant activity. Two new anthraquinone
      glycosides named emodin 1-O-beta-D-glucopyranosyl-(1 -> 2)-glucopyranoside (1)
      and aloemodin 8-O-beta-D-glucopyranosyl-(1 -> 6)-glucopyranoside (2) along with
      aloemodin 8-O-beta-D-glucopyranoside (3), emodin (4), aloemodin (5) and one
      flavonoid, quercetin-3-O-alpha-L-rhamnopyranoside, were isolated from the leaves
      of C. roxburghii. Structures of the isolated compounds were established by UV,
      HRESI-MS, and 1D/2D (1)H/(13)C NMR spectroscopy. The total extract and some
      isolated compounds were determined against DPPH (2,2-diphenyl-1-(2,4,6
      trinitrophenyl)hydrazinyl radical, for their free radical scavenging activity,
      the total alcoholic extract showed strong antioxidant activity while the two new
      compounds showed weak antioxidant activity.

PMID- 22975279
TI  - Structural and serological studies on the O-antigen show that Citrobacter youngae
      PCM1505 must be classified to a new Citrobacter O-serogroup.
AB  - The O-polysaccharide obtained by mild acid hydrolysis of the lipopolysaccharide
      of Citrobacter youngae PCM1505 was studied by sugar and methylation analyses
      along with 1D and 2D (1)H and (13)C NMR spectroscopies. The following structure
      of the tetrasaccharide repeating unit of the polysaccharide was established:
      [Formula: see text]. Structural and serological data obtained earlier and in this
      work show that the strain studied is a candidate to a new Citrobacter O
      serogroup.

PMID- 22975280
TI  - Efficacy of novel benznidazole solutions during the experimental infection with
      Trypanosoma cruzi.
AB  - Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. About 8
      million people throughout Latin America are infected causing approximately 10,000
      deaths annually. Benznidazole, available as unique 100 mg tablets in many of the
      endemic countries, is currently the drug of choice for the specific treatment of
      this condition. Despite of the large number of pediatric patients infected, there
      are no commercial liquid dosage forms available to treat this trypanosomiasis.
      This work showed that novel benznidazole-water-polyethylene glycol 400 solutions
      are active against T. cruzi in a murine model of Chagas' disease. Present results
      constitute the first demonstration on the usefulness of benznidazole solutions in
      infected mice.

PMID- 22975281
TI  - How the amyloid-beta peptide and membranes affect each other: an extensive
      simulation study.
AB  - The etiology of Alzheimer's disease is thought to be linked to interactions
      between amyloid-beta (Abeta) and neural cell membranes, causing membrane
      disruption and increased ion conductance. The effects of Abeta on lipid behavior
      have been characterized experimentally, but structural and causal details are
      lacking. We used atomistic molecular dynamics simulations totaling over 6 MUs in
      simulation time to investigate the behavior of Abeta(42) in zwitterionic and
      anionic lipid bilayers. We simulated transmembrane beta-sheets (monomer and
      tetramer) resulting from a global optimization study and a helical structure
      obtained from an NMR study. In all simulations Abeta(42) remained embedded in the
      bilayer. It was found that the surface charge and the lipid tail type are
      determinants for transmembrane stability of Abeta(42) with zwitterionic surfaces
      and unsaturated lipids promoting stability. From the considered structures, the
      beta-sheet tetramer is most stable as a result of interpeptide interactions. We
      performed an in-depth analysis of the translocation of water in the Abeta(42)
      bilayer systems. We observed that this process is generally fast (within a few
      nanoseconds) yet generally slower than in the peptide-free bilayers. It is mainly
      governed by the lipid type, simulation temperature and Abeta(42) conformation.
      The rate limiting step is the permeation through the hydrophobic core, where
      interactions between Abeta(42) and permeating H(2)O molecules slow the
      translocation process. The beta-sheet tetramer allows more water molecules to
      pass through the bilayer compared to monomeric Abeta, allowing us to conclude
      that the experimentally observed permeabilization of membranes must be due to
      membrane-bound Abeta oligomers, and not monomers.

PMID- 22975282
TI  - Modulation of low-voltage-activated T-type Ca2+ channels.
AB  - Low-voltage-activated T-type Ca2+ channels contribute to a wide variety of
      physiological functions, most predominantly in the nervous, cardiovascular and
      endocrine systems. Studies have documented the roles of T-type channels in sleep,
      neuropathic pain, absence epilepsy, cell proliferation and cardiovascular
      function. Importantly, novel aspects of the modulation of T-type channels have
      been identified over the last few years, providing new insights into their
      physiological and pathophysiological roles. Although there is substantial
      literature regarding modulation of native T-type channels, the underlying
      molecular mechanisms have only recently begun to be addressed. This review
      focuses on recent evidence that the Ca(v)3 subunits of T-type channels, Ca(v)3.1,
      Ca(v)3.2 and Ca(v)3.3, are differentially modulated by a multitude of endogenous
      ligands including anandamide, monocyte chemoattractant protein-1, endostatin, and
      redox and oxidizing agents. The review also provides an overview of recent
      knowledge gained concerning downstream pathways involving G-protein-coupled
      receptors. This article is part of a Special Issue entitled: Calcium channels.

PMID- 22975283
TI  - Utility of observation units for young emergency department chest pain patients.
AB  - BACKGROUND: Determining which patients presenting to the Emergency Department
      (ED) require further work-up for acute coronary syndrome (ACS) can be difficult.
      The utility of routine observation for cardiac testing in low-risk young adult
      patients has been questioned. STUDY OBJECTIVES: We investigated the rate of
      positive findings yielded by routine cardiac observation unit work-up in patients
      aged 40 years or younger. METHODS: This was a retrospective observational cohort
      study of patients aged 18-40 years who were evaluated for ACS in an ED-based
      observation unit. Data were collected by trained abstractors from electronic
      medical records. RESULTS: A total of 362 patients met inclusion criteria. Of
      those, 239 received stress testing, yielding five positive and nine indeterminate
      results. One other patient had acute troponin elevation while under observation.
      The positive stress test patients and troponin-elevated patient underwent cardiac
      angiography. Only one positive stress test patient showed significant coronary
      stenosis and received coronary interventions. In follow-up data, one patient had
      an adverse cardiac outcome within 1 year of index visit, but no coronary
      interventions. Thus, only 3 patients had adverse cardiac events, with only one
      patient warranting intervention discovered by observation unit stress testing and
      a second via serial cardiac markers. CONCLUSION: Routine observation of
      symptomatic young adults for ACS had low yield. Observation identified one
      patient with acute cardiac marker elevation and further stress testing identified
      only one patient with intervenable ACS, despite a high false-positive rate. This
      suggests that observation and stress testing should not be routinely performed in
      this demographic absent other high-risk features.

PMID- 22975284
TI  - Gastric aspirate fluorescence in ethylene glycol poisoning.

PMID- 22975285
TI  - Victims of bullying in the emergency department with behavioral issues.
AB  - BACKGROUND: Bullying has become one of the most significant school problems
      experienced by our children. Victims of bullying are prone to a variety of
      psychological and behavioral symptoms. We noted that many children referred to
      the Emergency Department (ED) with behavioral symptoms provided a history of
      bullying. OBJECTIVES: To measure the prevalence of bullying in children referred
      to the ED for behavioral symptoms and to determine its association with
      psychiatric disorders. METHODS: A retrospective cohort study was conducted in an
      urban hospital, identifying children from 8 to 19 years of age who presented to
      the ED with behavioral symptoms. We reviewed the ED psychiatry notes to retrieve
      the report indicating whether these children were bullied and had previous
      psychiatric diagnoses. These children were classified into bullied and non
      bullied groups. RESULTS: Over the study period, 591 children visited the ED with
      behavioral issues. Out of 591, 143 (24%) children reported bullying. More boys
      (100) than girls (43) reported bullying (p = 0.034). The mean age of children in
      the bullied group was 10.6 years (95% confidence interval 10.1-11.2). One hundred
      eleven (77.6%) children in the bullied group had a prior psychiatric diagnosis.
      Children in the bullied group were hospitalized significantly less than children
      in the non-bullied group (10/143 [7%] vs. 80/368 [18%]; p = 0.002). CONCLUSION:
      The prevalence of bullying among the ED children with behavioral symptoms is
      substantial. Every fourth child with behavioral symptoms reported bullying. Four
      in five children who reported bullying had a prior diagnosis of "disorder of
      behavior."

PMID- 22975286
TI  - At3g08030 transcript: a molecular marker of seed ageing.
AB  - BACKGROUND AND AIMS: Prolonged storage generally reduces seed viability and
      vigour, although the rate of deterioration varies among species and environmental
      conditions. Here, we suggest a possible ageing molecular marker: At3g08030 mRNA.
      At3g08030 is a member of the DUF642 highly conserved family of cell-wall
      associated proteins that is specific for spermatophytes. METHODS: At3g08030
      expression was performed by RT-PCR and qRT-PCR analysis in seed samples differing
      in their rate of germination and final germination following a matrix priming
      and/or controlled deterioration (rapid ageing) treatment. KEY RESULTS: The
      At3g08030 gene transcript was present during the entire Arabidopsis thaliana
      plant life cycle and in seeds, during maturation, the ripening period and after
      germination. Matrix priming treatment increased the rate of germination of
      control seeds and seeds aged by controlled deterioration. Priming treatments also
      increased At3g08030 expression. To determine whether the orthologues of this gene
      are also age markers in other plant species, At3g08030 was cloned in two wild
      species, Ceiba aesculifolia and Wigandia urens. As in A. thaliana, the At3g08030
      transcript was not present in aged seeds of the tested species but was present in
      recently shed seeds. A reduction in germination performance of the aged seeds
      under salt stress was determined by germination assays. CONCLUSIONS: At3g08030
      mRNA detection in a dry seed lot has potential for use as a molecular marker for
      germination performance in a variety of plant species.

PMID- 22975287
TI  - Comparison of germination and seed bank dynamics of dimorphic seeds of the cold
      desert halophyte Suaeda corniculata subsp. mongolica.
AB  - BACKGROUND AND AIMS: Differences in dormancy and germination requirements have
      been documented in heteromorphic seeds of many species, but it is unknown how
      this difference contributes to maintenance and regeneration of populations. The
      primary aim of this study was to compare the seed bank dynamics, including
      dormancy cycling, of the two seed morphs (black and brown) of the cold desert
      halophyte Suaeda corniculata and, if differences were found, to determine their
      influence on regeneration of the species. METHOD: Seeds of the two seed morphs
      were buried, exhumed and tested monthly for 24 months over a range of
      temperatures and salinities, and germination recovery and viability were
      determined after exposure to salinity and water stress. Seedling emergence and
      dynamics of the soil seed bank were also investigated for the two morphs. KEY
      RESULTS: Black seeds had an annual dormancy/non-dormancy cycle, while brown
      seeds, which were non-dormant at maturity, remained non-dormant. Black seeds also
      exhibited an annual cycle in sensitivity of germination to salinity. Seedlings
      derived from black seeds emerged in July and August and those from brown seeds in
      May. Seedlings were recruited from 2.6 % of the black seeds and from 2.8 % of the
      brown seeds in the soil, and only 0.5 % and 0.4 % of the total number of black
      and brown seeds in the soil, respectively, gave rise to seedlings that survived
      to produce seeds. Salinity and water stress induced dormancy in black seeds and
      decreased viability of brown seeds. Brown seeds formed only a transient soil seed
      bank and black seeds a persistent seed bank. CONCLUSIONS: The presence of a
      dormancy cycle in black but not in brown seeds of S. corniculata and differences
      in germination requirements of the two morphs cause them to differ in their
      germination dynamics. The study contributes to our limited knowledge of dormancy
      cycling and seed bank formation in species producing heteromorphic seeds.

PMID- 22975288
TI  - Effects of riluzole on harmaline induced tremor and ataxia in rats: biochemical,
      histological and behavioral studies.
AB  - Essential tremor (ET) is one of the most common and most disabling movement
      disorders among adults. The drug treatment of essential tremor remains
      unsatisfactory. Additional therapies are required for patients with inadequate
      response or intolerable side effects. Thus, we aimed to investigate the
      therapeutic effects of riluzole on harmaline-induced tremor and ataxia in rat,
      and determining whether riluzole exerts its effect through modulation of
      glutamate levels in cerebellum. The study included 5 groups of Wistar rats
      weighing 80-100g, injected with harmaline (50mg/kg i.p.) for inducing
      experimental tremors and ataxia. The rats in group 1 served as control (saline
      induced) and group 2 received harmaline alone, whereas the animals in groups 3, 4
      and 5, were also given riluzole intraperitoneally at doses of 2, 4 and 8 mg/kg 10
      min after harmaline administration, respectively. The intensity and duration of
      tremor were recorded. Rotarod test, distance traveled and number of crossings
      were used to evaluate motor performance. Results of this study demonstrated that
      riluzole dose dependently attenuated duration and intensity of harmaline-induced
      tremors. Also, riluzole significantly improves time to fall, distance traveled
      and number of crossings in combined riluzole and harmaline treated rats.
      Histological analysis indicated that harmaline could cause vermis Purkinje cell
      (PC) loss and riluzole prevented this toxic effect. Harmaline also could increase
      glutamate levels in vermis and treatment with riluzole restored glutamate levels.
      In conclusion, riluzole has relatively protective effects on harmaline-induced
      tremor, probably related to its inhibitory effect on glutamatergic
      neurotransmission.

PMID- 22975289
TI  - Structural analogs of pyrazole and sulfonamide cannabinoids: effects on acute
      food intake in mice.
AB  - Obesity contributes to a multitude of serious health problems. Given the
      demonstrated role of the endogenous cannabinoid system in appetite regulation,
      the purpose of the present study was to evaluate structural analogs of two
      cannabinoids, rimonabant (cannabinoid CB(1) receptor antagonist) and O-2050
      (sulfonamide analog of Delta(8)-tetrahydrocannabinol), that showed appetite
      suppressant effects in previous studies. Structure-activity relationships of
      these two lead compounds were examined in several assays, including cannabinoid
      CB(1) and CB(2) receptor binding, food intake, and an in vivo test battery
      (locomotor activity, antinociception, ring immobility, and body temperature) in
      mice. Rimonabant and O-2050 reliably decreased feeding in mice; however, their
      analogs decreased feeding only at higher doses, even though some compounds had
      quite good cannabinoid CB(1) binding affinity. Results of the in vivo test
      battery were inconsistent, with some of the compounds producing effects
      characteristic of cannabinoid agonists while other compounds were inactive or
      were antagonists against an active dose of Delta(9)-tetrahydrocannabinol. These
      results demonstrate that reduction of food intake is not a characteristic effect
      of pyrazole and sulfonamide cannabinoid analogs with favorable cannabinoid CB(1)
      binding affinity, suggesting that development of these classes of cannabinoids
      for the treatment of obesity will require evaluation of their effects in a broad
      spectrum of pharmacological assays.

PMID- 22975290
TI  - SUTAF, a novel beta-methoxyacrylate derivative, promotes neurite outgrowth with
      extracellular signal-regulated kinase and c-jun N-terminal kinase activation.
AB  - beta-Methoxyacrylate antibiotics are well known to inhibit the fungal and yeast
      mitochondrial respiratory chain. In addition, beta-methoxyacrylates are reported
      to suppress the proliferation of mammalian cancer cells. Differentiation and cell
      cycle arrest are closely related. The cell cycle of proliferating cells is
      suppressed before differentiation. In this study, we synthesized a beta
      methoxyacrylate analog and treated neuronal differential model cells with it. We
      then estimated beta-methoxyacrylate's neurotrophic effect by inhibiting cell
      proliferation so as to orient neuronal differentiation. SUTAF-027-a novel beta
      methoxyacrylate derivative, arrested the cell cycle and thereby suppressed the
      proliferation of PC12 rat pheochromocytoma cells and mouse neuroblastoma Neuro2a
      cells at very low treatment doses, as low as 1nM. However, a single SUTAF-027
      treatment did not affect neuritogenesis. Surprisingly, however, co-treatment of
      SUTAF-027 and nerve growth factor (NGF) significantly augmented the NGF-induced
      neurite outgrowth of PC12. On the other hand, a single treatment of 1nM SUTAF-027
      induced neurite outgrowth in Neuro2a cells. Further signal transduction mechanism
      studies revealed that SUTAF-027 induced the phosphorylation of extracellular
      signal-regulated kinase (ERK) and slight phosphorylation of c-jun N-terminal
      kinase (JNK). Moreover, inhibition of ERK and JNK blocked SUTAF-027-augmented
      neurite outgrowth. These results suggested that the novel beta-methoxyacrylate
      analog SUTAF-027 augmented neurite outgrowth by arresting the cell cycle and
      activating the ERK and JNK pathways.

PMID- 22975291
TI  - Redox imbalances incite the hypertensive, baroreflex, and autonomic effects of
      cyclosporine in rats.
AB  - Previous studies including ours showed that cyclosporine (CSA) causes baroreflex
      dysfunction and hypertension. Here we tested the hypothesis that oxidative damage
      in central and peripheral tissues underlies the hypertensive, baroreflex and
      autonomic actions elicited by CSA in rats. We investigated the effects of
      individual and combined 7-day treatments with CSA (25 mg/kg/day, n=7) and 4
      hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol, superoxide dismutase mimetic,
      100 mg/kg/day, n=7) on blood pressure, reflex heart rate responses to
      peripherally mediated pressor and depressor responses, and biomarkers of
      oxidative stress. CSA elevated blood pressure and reduced reflex bradycardic
      (phenylephrine) and tachycardic (sodium nitroptrusside) responses. The ability of
      muscarinic (atropine, 1 mg/kg i.v.) or beta-adrenoceptor blockade (propranolol, 1
      mg/kg i.v.) to reduce reflex heart rate responses was reduced in CSA-treated
      rats, suggesting the impairment by CSA of reflex cardiac autonomic control.
      Concurrent administration of tempol abolished CSA-induced hypertension and
      normalized the associated impairment in baroreflex gain and cardiac autonomic
      control. Tempol also reversed the CSA-induced increases in aortic and brainstem
      nitrite/nitrate and malondialdehyde (MDA) and decreases in aortic superoxide
      dismutase (SOD). These findings implicate oxidative stress in peripheral and
      central cardiovascular sites in the deleterious actions of CSA on blood pressure
      and baroreceptor control of heart rate.

PMID- 22975292
TI  - Discrepancies in military middle-school adolescents' and parents' perceptions of
      family functioning, social support, anger frequency, and concerns.
AB  - Previous literature suggests that adolescents' and parents' perceptions of family
      functioning are typically quite disparate and that perceptual discrepancies
      increase when a family is under stress. During the years of deployments to Iraq
      and Afghanistan adolescents in military families have faced uniquely stressful
      circumstances which may exacerbate difficulties commonly experienced during
      adolescence. For this study 91 middle-school adolescent-parent dyads from U.S.
      Army families were surveyed about their perceptions of family functioning, social
      support, the adolescent's frequency of anger, and the adolescent's concerns.
      Findings indicated significant differences in parents' and adolescents' matched
      ratings for all variables except adolescent concerns. Adolescent-parent
      perceptual discrepancies were greatest for families who had never experienced
      deployment and during or following the first deployment. The results of this
      study may be useful to those supporting military families as they develop
      strategies to help family members understand the others' perceptions and learn to
      communicate and solve problems despite the differences.

PMID- 22975293
TI  - Clinical imprinting: the impact of early clinical learning on career long
      professional development in nursing.
AB  - The literature recognises a relationship between clinical experience and a
      successful undergraduate experience in nursing; however what constitutes an
      effective approach remains the subject of debate, particularly in relation to
      first year of learning. There is evidence from a biological standpoint that early
      experience impacts on the behavioural development of animals, described by Konrad
      Lorenz (1903-1989) as 'imprinting'. The concept of imprinting has resonance for
      nursing. In this article the importance of 'getting it right at the beginning' is
      explored and what, if anything, Lorenz's theory tells us about the impact of
      early clinical learning on subsequent professional development.

PMID- 22975294
TI  - Serum level of thymic stromal lymphopoietin in allergic asthmatic children.

PMID- 22975295
TI  - Effect of transtibial prosthesis alignment changes on out-of-plane socket
      reaction moments during walking in amputees.
AB  - Alignment of lower limb prostheses is important for the gait of amputees.
      Observed deviations in a particular plane are corrected by altering the
      prosthetic alignment of the same plane. The assumption is that observed
      deviations are due to alignment errors within the same plane, but no research has
      confirmed this assumption. Therefore, the aim of this study was to investigate
      the out-of-plane effect of systematic alignment changes on socket reaction
      moments measured by an instrumented prosthesis alignment component in the
      sagittal and coronal planes in eleven amputees with transtibial prostheses. Each
      subject walked at self-selected walking speed following randomized controlled
      angular (+/-3 degrees  and +/-6 degrees ) and translational (+/-5 mm and +/-10
      mm) alignment changes from the nominally aligned condition. The following socket
      reaction moment parameters were subsequently analyzed: 3 parameters (maximum
      moment, minimum moment, moment at 45% of stance phase) in the sagittal plane and
      2 parameters (moment at 30% and 75% of stance phase) in the coronal plane. A
      statistical comparison was performed between the nominally aligned and mal
      aligned conditions using a repeated measures of ANOVA followed by Scheffe's post
      hoc tests. Significant differences were found between the nominally aligned (
      0.077+/-0.078 Nm/kg) and 3 degrees  extension (-0.033+/-0.075 Nm/kg; P=0.0258)
      and 6 degrees  extension (-0.029+/-0.071 Nm/kg; P=0.0098) conditions in the
      coronal plane socket reaction moments measured at 30% of stance. Our analysis
      suggests that the alignment of the transtibial prosthesis should be performed in
      the sagittal plane first followed by the coronal plane.

PMID- 22975296
TI  - Genetic analysis of reaction time variability: room for improvement?
AB  - BACKGROUND: Increased reaction time variability (RTV) on cognitive tasks
      requiring a speeded response is characteristic of several psychiatric disorders.
      In attention deficit hyperactivity disorder (ADHD), the association with RTV is
      strong phenotypically and genetically, yet high RTV is not a stable impairment
      but shows ADHD-sensitive improvement under certain conditions, such as those with
      rewards. The state regulation theory proposed that the RTV difference score,
      which captures change from baseline to a rewarded or fast condition, specifically
      measures 'state regulation'. By contrast, the interpretation of RTV baseline
      (slow, unrewarded) scores is debated. We aimed to investigate directly the degree
      of phenotypic and etiological overlap between RTV baseline and RTV difference
      scores. Method We conducted genetic model fitting analyses on go/no-go and fast
      task RTV data, across task conditions manipulating rewards and event rate, from a
      population-based twin sample (n=1314) and an ADHD and control sibling-pair sample
      (n=1265). RESULTS: Phenotypic and genetic/familial correlations were consistently
      high (0.72-0.98) between RTV baseline and difference scores, across tasks,
      manipulations and samples. By contrast, correlations were low between RTV in the
      manipulated condition and difference scores. A comparison across two different
      go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high
      phenotypic and genetic/familial overlap (r = 0.75-0.83). CONCLUSIONS: Our finding
      that RTV difference scores measure largely the same etiological process as RTV
      under baseline condition supports theories emphasizing the malleability of the
      observed high RTV. Given the statistical shortcomings of difference scores, we
      recommend the use of RTV baseline scores for most analyses, including genetic
      analyses.

PMID- 22975297
TI  - Sarcopenia is related to increased risk for low bone mineral density.
AB  - Lean body mass is positively correlated with bone mineral density (BMD). The
      association between sarcopenia and BMD is less studied. The aim of the study is
      to investigate the association between sarcopenia and abnormal BMD. A total of
      600 community residents aged 40-85 years (mean=63.63 +/- 10.12) from Taipei,
      Taiwan were included. Abnormal and normal BMD groups were categorized by T-score
      of femoral neck and lumbar spine (L2-L4) measured by dual-energy X-ray
      absorptiometry. Skeletal muscle mass (SM) index (SMI) was obtained from SM
      divided by height squared using bioelectrical impedance analysis (BIA) method.
      Sarcopenia was defined as SMI less than 8.87 kg/m2 in men and 6.42 kg/m2 in women
      according to previous Taiwanese sarcopenia study. The association between BMD
      groups and sarcopenia was examined using binary logistic regression analyses
      after controlling potential confounders. Subjects with sarcopenia were at higher
      risk for low BMD (odds ratio (OR) = 1.59, 95% confidence interval (CI)=1.06-2.39
      for femoral neck BMD and OR=1.72, 95% CI=1.09-2.72 for lumbar BMD) compared with
      the nonsarcopenia group. Even in different gender groups with age categorized,
      sarcopenia was still an important independent factor in female group. The least
      square (LS) means of BMD of femoral neck and lumbar spine were significantly
      lower in sarcopenia group. The risk of low BMD increased significantly with
      sarcopenia.

PMID- 22975298
TI  - The development and validation of a risk score for household infestation by
      Triatoma infestans, a Bolivian vector of Chagas disease.
AB  - Chagas disease, primarily spread in Bolivia by the vector Triatoma Infestans,
      persists as an important public health problem. Preventative insecticide
      campaigns target spraying on the basis of anecdotal evidence and there is a need
      for an accurate classification score to correctly identify 'at risk' houses. Data
      were collected from 337 households on 11 variables through the use of a
      standardised questionnaire and survey. Risk factors for infestation were
      identified and a risk score was developed and validated on a separate cohort of
      165 houses. Five significant risk factors were identified: cracks in the walls of
      houses; adobe walls; junk in the peridomiciliary area; no insecticide spraying in
      the previous two years; and freely ranging animals. A risk score was generated
      and then calculated for each house. Three risk categories were defined: low,
      medium and high risk. In the development cohort the infestation rates were 2%,
      18% and 69% respectively. The corresponding infestation rates in the validation
      cohort were 7%, 30% and 75% respectively. Sensitivity and specificity for this
      test were 81% and 84% and the positive predictive and negative predictive values
      were 71% and 90%. The risk score developed could be used to inform decision
      making in underfunded multilateral preventative initiatives.

PMID- 22975299
TI  - Synthesis of highly water-soluble fibrate derivatives via BGLation.
AB  - Three water-soluble fibrates (fenofibrate, bezafibrate and chlofibrate)
      conjugated with a symmetrically branched glyceryl trimer (BGL003) were
      synthesized, and an evaluation of the fenofibrate-BGL003 conjugate as a candidate
      for anti-hyperlipemia drug was carried out using rats. The water-solubility of
      the fenofibrate-BGL003 conjugate was several thousand times greater than that of
      the original fenofibrate. The lipid-lowering effects of the fenofibrate-BGL003
      conjugate were as strong as those of the same grams of fenofibrate. The actual
      active species of fenofibrate, fenofibric acid, was detected in rats' blood, but
      neither the fenofibrate-BGL003 conjugate nor fenofibrate was detected, probably
      due to enzymatic hydrolysis of the ester bond. The plasma concentration of
      fenofibric acid derived from the fenofibrate-BGL003 conjugate was five times
      higher than that derived from fenofibrate 4h after administration.

PMID- 22975300
TI  - Transformation of 8-prenylnaringenin by Absidia coerulea and Beauveria bassiana.
AB  - Beauveria bassiana AM278 and Absidia coerulea AM93 converted 8-prenylnaringenin
      (1) into two glycoside derivatives (7-O-beta-D-glucopyranoside) (2) and 7-O-beta
      D-4'''-O-methylglucopyranoside) (3) in high yields in processes conducted in
      Saboraud medium. 8-Prenylnaringenin 7-O-beta-D-4'''-O-methylglucopyranoside (3)
      is a new compound. 8-Prenylnaringenin-7-sulfate (4) was obtained in
      transformation of 1 by Absidia coerulea AM93 in a buffer. Formation of conjugated
      products in this study proceeds in a manner analogous to mammalian systems which
      indicates the potential use of microbes to mimic mammalian metabolism.

PMID- 22975301
TI  - Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators.
AB  - A novel series of aryl azetidinyl oxadiazoles are identified as mGluR5 positive
      allosteric modulators (PAMs) with improved physico-chemical properties. N
      substituted cyclohexyl and exo-norbornyl carboxamides, and carbamate analogs of
      azetidines are moderate to potent mGluR5 PAMs. The aryl, lower alkyl carboxamides
      analogs and sulfonamide analogs of azetidines are moderate mGluR5 negative
      allosteric modulators (NAMs). In the aryl oxadiazole moiety, substituents such as
      fluoro, chloro and methyl are well tolerated at the meta position while para
      substituents led to either inactive compounds or NAMs. A tight pharmacophore and
      subtle 'PAM to NAM switching' with close analogs makes the optimization of the
      series extremely challenging.

PMID- 22975302
TI  - Serum stability of selected decapeptide agonists of KISS1R using pseudopeptides.
AB  - Metastin/kisspeptin, a 54-amino acid peptide, is the ligand of the G-protein
      coupled receptor KISS1R which plays a key role in pathways that regulate
      reproduction and cell migration in many endocrine and gonadal tissues. The N
      terminally truncated decapeptide, metastin(45-54), has 3-10 times higher receptor
      affinity and intracellular calcium ion-mobilizing activity but is rapidly
      inactivated in serum. In this study we designed and synthesized stable KISS1R
      agonistic decapeptide analogs with selected substitutions at positions 47, 50,
      and 51. Replacement of glycine with azaglycine (azaGly) in which the alpha-carbon
      is replaced with a nitrogen atom at position 51 improved the stability of amide
      bonds between Phe(50)-Gly(51) and Gly(51)-Leu(52) as determined by in vitro mouse
      serum stability studies. Substitution for tryptophan at position 47 with other
      amino acids such as serine, threonine, beta-(3-pyridyl)alanine, and D-tryptophan
      (D-Trp), produced analogs that were highly stable in mouse serum. D-Trp(47)
      analog 13 showed not only high metabolic stability but also excellent KISS1R
      agonistic activity. Other labile peptides may have increased serum stability
      using amino acid substitution.

PMID- 22975304
TI  - Chitosan/TPP microparticles obtained by microemulsion method applied in
      controlled release of heparin.
AB  - This work deals with the preparation of chitosan/tripolyphosphate microparticles
      (CHT/TPP) using microemulsion system based on water/benzyl alcohol. The
      morphology of the microparticles was evaluated by scanning electron microscopy
      (SEM). The microparticles were also characterized through infrared spectroscopy
      (FTIR) and wide-angle X-ray scattering (WAXS). The morphology and crystallinity
      of microparticles depended mainly on CHT/TPP ratio. Studies of controlled release
      of HP were evaluated in distilled water and in simulated gastric fluid. Besides,
      the profile of HP releasing could be tailored by tuning the CHT/TPP molar ratio.
      Finally, these prospective results allow the particles to be employed as site
      specific HP controlled release system.

PMID- 22975303
TI  - A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to
      azole antifungal drugs.
AB  - The high-affinity reductive iron uptake system that includes a ferroxidase (Cfo1)
      and an iron permease (Cft1) is critical for the pathogenesis of Cryptococcus
      neoformans. In addition, a mutant lacking CFO1 or CFT1 not only has reduced iron
      uptake but also displays a markedly increased susceptibility to azole antifungal
      drugs. Altered antifungal susceptibility of the mutants was of particular
      interest because the iron uptake system has been proposed as an alternative
      target for antifungal treatment. In this study, we used transcriptome analysis to
      begin exploring the molecular mechanisms of altered antifungal susceptibility in
      a cfo1 mutant. The wild-type strain and the cfo1 mutant were cultured with or
      without the azole antifungal drug fluconazole and their transcriptomes were
      compared following sequencing with Illumina Genome Analyzer IIx (GAIIx)
      technology. As expected, treatment of both strains with fluconazole caused
      elevated expression of genes in the ergosterol biosynthetic pathway that includes
      the target enzyme Erg11. Additionally, genes differentially expressed in the cfo1
      mutant were involved in iron uptake and homeostasis, mitochondrial functions and
      respiration. The cfo1 mutant also displayed phenotypes consistent with these
      changes including a reduced ratio of NAD(+)/NADH and down-regulation of Fe-S
      cluster synthesis. Moreover, combination treatment of the wild-type strain with
      fluconazole and the respiration inhibitor diphenyleneiodonium dramatically
      increased susceptibility to fluconazole. This result supports the hypothesis that
      down-regulation of genes required for respiration contributed to the altered
      fluconazole susceptibility of the cfo1 mutant. Overall, our data suggest that
      iron uptake and homeostasis play a key role in antifungal susceptibility and
      could be used as novel targets for combination treatment of cryptococcosis.
      Indeed, we found that iron chelation in combination with fluconazole treatment
      synergistically inhibited the growth of C. neoformans.

PMID- 22975305
TI  - Tracking the complete revolution of Surface Westerlies over Northern Hemisphere
      using radionuclides emitted from Fukushima.
AB  - Massive amounts of anthropogenic radionuclides were released from the nuclear
      reactors located in Fukushima (northeastern Japan) between 12 and 16 March 2011
      following the earthquake and tsunami. Ground level air radioactivity was
      monitored around the globe immediately after the Fukushima accident. This global
      effort provided a unique opportunity to trace the surface air mass movement at
      different sites in the Northern Hemisphere. Based on surface air radioactivity
      measurements around the globe and the air mass backward trajectory analysis of
      the Fukushima radioactive plume at various places in the Northern Hemisphere by
      employing the Hybrid Single-Particle Lagrangian Integrated Trajectory model, we
      show for the first time, that the uninterrupted complete revolution of the mid
      latitude Surface Westerlies took place in less than 21 days, with an average
      zonal velocity of>60 km/h. The position and circulation time scale of Surface
      Westerlies are of wide interest to a large number of global researchers including
      meteorologists, atmospheric researchers and global climate modellers.

PMID- 22975306
TI  - Nutrient fluxes via submarine groundwater discharge to the Bay of Puck, southern
      Baltic Sea.
AB  - Submarine groundwater discharge (SGD) has been recognized as an important
      exchange pathway between hydrologic reservoirs due to its impact on
      biogeochemical cycles of the coastal ocean. This study reports nutrient
      concentrations and loads delivered by SGD into the Bay of Puck, the southern
      Baltic Sea. Measurements were carried out between September, 2009 and October,
      2010 at groundwater seepage sites identified by low salinity of pore water.
      Groundwater fluxes, measured using seepage meters, ranged from 3 to 22 L m(
      2)day(-1). Average concentrations of nutrients in groundwater samples collected
      were as follows: 0.4 MUmol L(-1) nitrate (NO(3)), 0.8 MUmol L(-1) nitrite
      (NO(2)), 18.2 MUmol L(-1) ammonium (NH(4)) and 60.6 MUmol L(-1) orthophosphate
      (PO(4)). Levels of NH(4) and PO(4) were significantly higher in samples from SGD
      sites than in seawater. Seawater and SGD samples showed similar NO(2)
      concentrations but SGD samples exhibited lower NO(3) levels than those observed
      in seawater samples. Measured seepage water fluxes and nutrient concentrations
      were used to calculate nutrient loads discharged into the study area while the
      literature groundwater flux and the measured nutrient concentrations were used to
      estimate nutrient loads discharged into the Bay of Puck. The estimates suggest
      that SGD delivers a dissolved inorganic nitrogen (DIN) load of 49.9 +/- 18.0 t
      yr(-1) and a PO(4)(-) load of 56.3 +/- 5.5tyr(-1) into the Bay of Puck. The
      projected estimates are significant in comparison with loads delivered to the bay
      from other, well-recognized sources (705 ty r(-1) and 105 ty r(-1) respectively
      for DIN and PO(4)). Nutrient discharge input loads were projected to the entire
      Baltic Sea The extrapolated values indicate SGD contributes a significant
      proportion of phosphate load but only an insignificant proportion of DIN load.
      Further studies are necessary to better understand SGD contributions to the
      nutrient budget in the Baltic Sea.

PMID- 22975307
TI  - Solid waste deposits as a significant source of contaminants of emerging concern
      to the aquatic and terrestrial environments - a developing country case study
      from Owerri, Nigeria.
AB  - In developing countries, there are needs for scientific basis to sensitize
      communities on the problems arising from improper solid waste deposition and the
      acute and long-term consequences for areas receiving immobilized pollutants. In
      Nigeria, as in many other African countries, solid waste disposal by way of open
      dumping has been the only management option for such wastes. Herein, we have
      highlighted the challenges of solid waste deposit and management in developing
      countries, focusing on contaminants of emerging concern and leaching into the
      environment. We have analyzed sediments and run-off water samples from a solid
      waste dumping site in Owerri, Nigeria for organic load and compared these with
      data from representative world cities. Learning from previous incidents, we
      intend to introduce some perspective for awareness of contaminants of emerging
      concerns such as those with potential endocrine disrupting activities in wildlife
      and humans. Qualitative and quantitative data obtained by gas chromatography and
      mass spectrometric analysis (GC-MS) provide an overview on lipophilic and semi
      polar substances released from solid waste, accumulated in sediments and
      transported via leachates. The chromatograms of the full scan analyses of the
      sediment extracts clearly point to contamination related to heavy oil. The
      homologous series of n-alkanes with chain lengths ranging between C16 and C30, as
      well as detected polyaromatic hydrocarbon (PAH) compounds such as anthracene,
      phenanthrene, fluoranthene and pyrene support the assumption that diesel fuel or
      high boiling fractions of oil are deposited on the site. Targeted quantitative
      analysis for selected compounds showed high concentration of substances typically
      released from man-made products such as plastics, textiles, household and
      consumer products. Phthalate, an integral component of plastic products, was the
      dominant compound group in all sediment samples and run-off water samples.
      Technical nonylphenols (mixture of isomers), metabolites of non-ionic surfactants
      (nonylphenol-polyethoxylates), UV-filter compound ethyl methoxy cinnamate (EHMC)
      and bisphenol A (BPA) were particularly determined in the sediment samples at
      high MUg/kg dry weight concentration. Measuring contaminants in such areas will
      help in increasing governmental, societal and industrial awareness on the extent
      and seriousness of the contamination both at waste disposal sites and surrounding
      terrestrial and aquatic environments.

PMID- 22975308
TI  - Solid-in-oil dispersion: a novel core technology for drug delivery systems.
AB  - Drug delivery systems using a solid-in-oil (S/O) dispersion as a core technology
      have advanced significantly over the past ten years. A novel, effective and
      practical preparation method for a S/O dispersion was originally established in
      1997 as a tool for enzymatic catalysis in organic media. This oil-based
      dispersion containing proteins in non-aqueous media had great potential for
      applications to other research with one of the most successful being its
      adaptation as a drug delivery system. The history and features of novel processes
      for preparing S/O dispersions are presented in this article. In addition, recent
      research into the use of S/O dispersions for innovative oral and skin drug
      delivery systems is discussed.

PMID- 22975309
TI  - Break force and tensile strength relationships for curved faced tablets subject
      to diametrical compression.
AB  - The break force of flat faced tablets subject to diametrical compression (often
      referred to as "hardness") can be related to the tensile strength of the material
      using the Hertz contact theory. For curved tablets analytical solutions do not
      exist and an empirical equation developed by Pitt and Newton (1988) is usually
      used. In this paper we measure the break force of curved faced tablets having a
      range of curvatures pressed at various compaction forces. An empirical equation
      is proposed to relate the break force of curved faced tablets to the material
      tensile strength. The proposed equation is simplified and reduced to a form that
      is consistent with developed by Hertz theory for flat faced tablets.

PMID- 22975310
TI  - The microtubule associated protein syntabulin is required for glucose-stimulated
      and cAMP-potentiated insulin secretion.
AB  - Syntabulin is a microtubule-associated protein that mediates anterograde
      transport of vesicles to neuronal processes. Here, we found that syntabulin was
      expressed in mouse pancreas and insulin-secreting beta-cells, and that it
      partially co-localized with microtubule and insulin-containing granules. The
      association of syntabulin with these organelles increased upon glucose
      stimulation. Knock-down of syntabulin by shRNA reduced both basal and glucose
      stimulated insulin secretion, and diminished cAMP-Epac2 and cAMP-PKA potentiated
      insulin secretion. Additionally, syntabulin was preferentially phosphorylated by
      the Epac2 agonist 8-pCPT-2'-O-Me-cAMP, suggesting that syntabulin could be a
      novel effector of Epac2 and play a critical role in cAMP-enhanced insulin
      secretion.

PMID- 22975311
TI  - Constitutive autotaxin transcription by Nmyc-amplified and non-amplified
      neuroblastoma cells is regulated by a novel AP-1 and SP-mediated mechanism and
      abrogated by curcumin.
AB  - The motility, angiogenesis and metastasis-stimulating factor Autotaxin (Atx),
      over expressed by human neuroblastomas (NB), is constitutively expressed by human
      Nmyc-amplified SK-N-BE and non-Nmyc-amplified SH-SY5Y NB cells. Here, we
      characterise a novel Atx transcriptional mechanism, utilised by both cell lines,
      that is restricted to the first 285bp of the Atx promoter and involves AP-1 and
      SP transcription factors, acting through a CRE/AP-1-like element at position -142
      to -149 and a GAbox at position -227 to -235 relative to the Atx translational
      start site. This novel transcriptional mechanism can be inhibited by internally
      initiated SP-3 and the natural phenol curcumin.

PMID- 22975312
TI  - Crystal structure analysis of the translation factor RF3 (release factor 3).
AB  - The bacterial translational GTPases release factor RF3 promotes translation
      termination by recycling RF1 or RF2. Here, we present the crystal structures of
      RF3 complexed with GDP and guanosine 3',5'-(bis)diphosphate (ppGpp) at
      resolutions of 1.8 and 3.0A, respectively. ppGpp is involved in the so-called
      "stringent response" of bacteria. ppGpp binds at the same site as GDP, suggesting
      that GDP and ppGpp are two alternative physiologically relevant ligands of RF3.
      We also found that ppGpp decelerates the recycling of RF1 by RF3. These lines of
      evidence suggest that RF3 functions both as a cellular metabolic sensor and as a
      regulator.

PMID- 22975313
TI  - Modelling, abstraction, and computation in systems biology: A view from computer
      science.
AB  - Systems biology is centrally engaged with computational modelling across multiple
      scales and at many levels of abstraction. Formal modelling, precise and
      formalised abstraction relationships, and computation also lie at the heart of
      computer science--and over the past decade a growing number of computer
      scientists have been bringing their discipline's core intellectual and
      computational tools to bear on biology in fascinating new ways. This paper
      explores some of the apparent points of contact between the two fields, in the
      context of a multi-disciplinary discussion on conceptual foundations of systems
      biology.

PMID- 22975314
TI  - Publication bias in clinical trials of electronic health records.
AB  - OBJECTIVE: To measure the rate of non-publication and assess possible publication
      bias in clinical trials of electronic health records. METHODS: We searched
      ClinicalTrials.gov to identify registered clinical trials of electronic health
      records and searched the biomedical literature and contacted trial investigators
      to determine whether the results of the trials were published. Publications were
      judged as positive, negative, or neutral according to the primary outcome.
      RESULTS: Seventy-six percent of trials had publications describing trial results;
      of these, 74% were positive, 21% were neutral, and 4% were negative (harmful). Of
      unpublished studies for which the investigator responded, 43% were positive, 57%
      were neutral, and none were negative; the lower rate of positive results was
      significant (p<0.001). CONCLUSION: The rate of non-publication in electronic
      health record studies is similar to that in other biomedical studies. There
      appears to be a bias toward publication of positive trials in this domain.

PMID- 22975315
TI  - Validating the semantics of a medical iconic language using ontological
      reasoning.
AB  - To help clinicians read medical texts such as clinical practice guidelines or
      drug monographs, we proposed an iconic language called VCM. This language can use
      icons to represent the main medical concepts, including diseases, symptoms,
      treatments and follow-up procedures, by combining various pictograms, shapes and
      colors. However, the semantics of this language have not been formalized, and
      users may create inconsistent icons, e.g. by combining the "tumor" shape and the
      "sleeping" pictograms into a "tumor of sleeping" icon. This work aims to
      represent the VCM language using DLs and OWL for evaluating its semantics by
      reasoners, and in particular for determining inconsistent icons. We designed an
      ontology for formalized the semantics of VCM icons using the Protege editor and
      scripts for translating the VCM lexicon in OWL. We evaluated the ability of the
      ontology to determine icon consistency for a set of 100 random icons. The
      evaluation showed good results for determining icon consistency, with a high
      sensitivity. The ontology may also be useful for the design of mapping between
      VCM and other medical terminologies, for generating textual labels for icons, and
      for developing user interfaces for creating VCM icons.

PMID- 22975316
TI  - Inlay "butterfly" cartilage tympanoplasty.
AB  - OBJECTIVES: The aim of this study was to analyze the outcome of inlay "butterfly"
      cartilage tympanoplasty. METHODS: The files of 42 patients (24 were male, 18 were
      female) who underwent primary or revision inlay butterfly cartilage tympanoplasty
      in 2005 to 2011 at a tertiary medical center were reviewed. Patients were
      regularly observed by otoscopy and audiometry. RESULTS: The mean patient age was
      27 years (range, 14-75 years), and the mean duration of follow-up was 24 months
      (range, 3-36 months). The postoperative period was uneventful. The technical
      (anatomical) success rate was 92% at 1 year. There was a significant decrease in
      the mean air-bone gap in 32 patients (preoperatively, 49.6 dB; postoperatively,
      26.2 dB; P = .006). Results were suboptimal in 3 patients with persistent small
      perforations of the operated ear. CONCLUSION: Inlay butterfly cartilage
      tympanoplasty appears to be effective in terms of defect closure and improved
      hearing, comparable with temporalis fascia graft tympanoplasty. Follow-up is
      necessary for at least 1 year when some perforation may reappear.

PMID- 22975317
TI  - Orienting the direction of EGFR activation.
AB  - Morphogens are typically distributed symmetrically from their source of
      production. In this issue of Developmental Cell, Peng et al. (2012) demonstrate
      that a bias in the directionality of protrusions emanating from cells secreting
      the EGFR ligand Spitz leads to asymmetric activation of the pathway.

PMID- 22975318
TI  - S1P1 bridges mechanotransduction and angiogenesis during vascular development.
AB  - Mechanisms of stabilization of the vascular plexus and the role of
      mechanotransduction in this process are not well understood. In this issue of
      Developmental Cell, Jung et al. (2012) and Gaengel et al. (2012) describe the
      ligand-sensitive and mechanosensitive functions of an important vascular G
      protein-coupled receptor, S1P1.

PMID- 22975319
TI  - How to fine-tune an epigenetic switch.
AB  - Arabidopsis does not flower in winter because FLC represses flowering genes, but
      prolonged cold exposure silences FLC, allowing flowering in spring. How do plants
      recalibrate this switch to adapt to different climates? Reporting in Science,
      Coustham et al. (2012) found that tweaking a Polycomb target sequence may do the
      trick.

PMID- 22975320
TI  - A ubiquitin-binding rhomboid protease aimed at ERADication.
AB  - Proteins are degraded from the ER by endoplasmic reticulum-associated degradation
      (ERAD). In a recent issue of Molecular Cell, Fleig et al. (2012) describe a role
      for a ubiquitin-binding rhomboid protease, RHBDL4, in degradation of select ERAD
      substrates. These findings and the significance of rhomboids and other
      intramembrane proteases are discussed.

PMID- 22975321
TI  - Governance of endocytic trafficking and signaling by reversible ubiquitylation.
AB  - The endosomal pathway provides a major platform for ubiquitin-modifying enzymes,
      which act upon membrane-associated proteins in transit. Ubiquitylated cargo
      proteins are recognized by ubiquitin-binding domains inherent to key adaptor
      proteins at the plasma membrane and sorting endosome. A balance between
      ubiquitylation and deubiquitylation activities may govern the efficiency of
      recycling from endosomes to the plasma membrane versus lysosomal sorting through
      the multivesicular body pathway. We discuss the current knowledge of the
      properties of adaptors and ubiquitin-modifying proteins and their effects upon
      the trafficking and signaling of receptors and ligands associated with pathways
      fundamental to development.

PMID- 22975323
TI  - Coordinated lumen contraction and expansion during vulval tube morphogenesis in
      Caenorhabditis elegans.
AB  - Morphogenesis is a developmental phase during which cell fates are executed.
      Mechanical forces shaping individual cells play a key role during tissue
      morphogenesis. By investigating morphogenesis of the Caenorhabditis elegans
      hermaphrodite vulva, we show that the force-generating actomyosin network is
      differentially regulated by NOTCH and EGFR/RAS/MAPK signaling to shape the vulval
      tube. NOTCH signaling activates expression of the RHO kinase LET-502 in the
      secondary cell lineage through the ETS-family transcription factor LIN-1. LET-502
      induces actomyosin-mediated contraction of the apical lumen in the secondary
      toroids, thereby generating a dorsal pushing force. In contrast, MAPK signaling
      in the primary lineage downregulates LET-502 RHO kinase expression to prevent
      toroid contraction and allow the gonadal anchor cell to expand the dorsal lumen
      of the primary toroids. The antagonistic action of the MAPK and NOTCH pathways
      thus controls vulval tube morphogenesis linking cell fate specification to
      morphogenesis.

PMID- 22975322
TI  - Radial construction of an arterial wall.
AB  - Some of the most serious diseases involve altered size and structure of the
      arterial wall. Elucidating how arterial walls are built could aid understanding
      of these diseases, but little is known about how concentric layers of muscle
      cells and the outer adventitial layer are assembled and patterned around
      endothelial tubes. Using histochemical, clonal, and genetic analysis in mice,
      here we show that the pulmonary artery wall is constructed radially, from the
      inside out, by two separate but coordinated processes. One is sequential
      induction of successive cell layers from surrounding mesenchyme. The other is
      controlled invasion of outer layers by inner layer cells through developmentally
      regulated cell reorientation and radial migration. We propose that a radial
      signal gradient controls these processes and provide evidence that PDGF-B and at
      least one other signal contribute. Modulation of such radial signaling pathways
      may underlie vessel-specific differences and pathological changes in arterial
      wall size and structure.

PMID- 22975324
TI  - Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to
      induce apoptosis during epithelial homeostasis.
AB  - A fundamental aspect of epithelial homeostasis is the dependence on specific
      growth factors for cell survival, yet the underlying mechanisms remain obscure.
      We found an "inverse" mode of receptor tyrosine kinase signaling that directly
      links ErbB receptor inactivation to the induction of apoptosis. Upon ligand
      deprivation Mig6 dissociates from the ErbB receptor and binds to and activates
      the tyrosine kinase c-Abl to trigger p73-dependent apoptosis in mammary
      epithelial cells. Deletion of Errfi1 (encoding Mig6) and inhibition or RNAi
      silencing of c-Abl causes impaired apoptosis and luminal filling of mammary
      ducts. Mig6 activates c-Abl by binding to the kinase domain, which is prevented
      in the presence of epidermal growth factor (EGF) by Src family kinase-mediated
      phosphorylation on c-Abl-Tyr488. These results reveal a receptor-proximal switch
      mechanism by which Mig6 actively senses EGF deprivation to directly activate
      proapoptotic c-Abl. Our findings challenge the common belief that deprivation of
      growth factors induces apoptosis passively by lack of mitogenic signaling.

PMID- 22975325
TI  - PKD controls alphavbeta3 integrin recycling and tumor cell invasive migration
      through its substrate Rabaptin-5.
AB  - Integrin recycling is critical for cell migration. Protein kinase D (PKD)
      mediates signals from the platelet-derived growth factor receptor (PDGF-R) to
      control alphavbeta3 integrin recycling. We now show that Rabaptin-5, a Rab5
      effector in endosomal membrane fusion, is a PKD substrate. PKD phosphorylates
      Rabaptin-5 at Ser407, and this is both necessary and sufficient for PDGF
      dependent short-loop recycling of alphavbeta3, which in turn inhibits alpha5beta1
      integrin recycling. Rab4, but not Rab5, interacts with phosphorylated Rabaptin-5
      toward the front of migrating cells to promote delivery of alphavbeta3 to the
      leading edge, thereby driving persistent cell motility and invasion that is
      dependent on this integrin. Consistently, disruption of Rabaptin-5 Ser407
      phosphorylation reduces persistent cell migration in 2D and alphavbeta3-dependent
      invasion. Conversely, invasive migration that is dependent on alpha5beta1
      integrin is promoted by disrupting Rabaptin phosphorylation. These findings
      demonstrate that the PKD pathway couples receptor tyrosine kinase signaling to an
      integrin switch via Rabaptin-5 phosphorylation.

PMID- 22975326
TI  - Lipid sorting by ceramide structure from plasma membrane to ER for the cholera
      toxin receptor ganglioside GM1.
AB  - The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it
      retrograde from the plasma membrane (PM) through endosomes, the trans-Golgi
      (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a
      membrane lipid can specify trafficking in these pathways, we synthesized GM1
      isoforms with alternate ceramide domains and imaged their trafficking in live
      cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN
      and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable,
      but membrane cholesterol and the lipid raft-associated proteins actin and
      flotillin were required. The results implicate a protein-dependent mechanism of
      lipid sorting by ceramide structure and provide a molecular explanation for the
      diversity and specificity of retrograde trafficking by CT in host cells.

PMID- 22975327
TI  - The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by
      regulating the interplay between VE-cadherin and VEGFR2.
AB  - Angiogenesis, the process by which new blood vessels arise from preexisting ones,
      is critical for embryonic development and is an integral part of many disease
      processes. Recent studies have provided detailed information on how angiogenic
      sprouts initiate, elongate, and branch, but less is known about how these
      processes cease. Here, we show that S1PR1, a receptor for the blood-borne
      bioactive lipid sphingosine-1-phosphate (S1P), is critical for inhibition of
      angiogenesis and acquisition of vascular stability. Loss of S1PR1 leads to
      increased endothelial cell sprouting and the formation of ectopic vessel
      branches. Conversely, S1PR1 signaling inhibits angiogenic sprouting and enhances
      cell-to-cell adhesion. This correlates with inhibition of vascular endothelial
      growth factor-A (VEGF-A)-induced signaling and stabilization of vascular
      endothelial (VE)-cadherin localization at endothelial junctions. Our data suggest
      that S1PR1 signaling acts as a vascular-intrinsic stabilization mechanism,
      protecting developing blood vessels against aberrant angiogenic responses.

PMID- 22975328
TI  - Flow-regulated endothelial S1P receptor-1 signaling sustains vascular
      development.
AB  - During angiogenesis, nascent vascular sprouts fuse to form vascular networks,
      enabling efficient circulation. Mechanisms that stabilize the vascular plexus are
      not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid
      mediator implicated in the regulation of vascular and immune systems. Here we
      describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1)
      stabilizes the primary vascular network. A gradient of S1P1 expression from the
      mature regions of the vascular network to the growing vascular front was
      observed. In the absence of endothelial S1P1, adherens junctions are
      destabilized, barrier function is breached, and flow is perturbed, resulting in
      abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as
      laminar shear stress to transduce flow-mediated signaling in endothelial cells
      both in vitro and in vivo. These data demonstrate that blood flow and circulating
      S1P activate endothelial S1P1 to stabilize blood vessels in development and
      homeostasis.

PMID- 22975329
TI  - Sef is an inhibitor of proinflammatory cytokine signaling, acting by cytoplasmic
      sequestration of NF-kappaB.
AB  - The NF-kappaB transcription factor controls diverse biological processes.
      According to the classical model, NF-kappaB is retained in the cytoplasm of
      resting cells via binding to inhibitory, IkappaB proteins and translocates into
      the nucleus upon their ligand-induced degradation. Here we reveal that Sef, a
      known tumor suppressor and inhibitor of growth factor signaling, is a spatial
      regulator of NF-kappaB. Sef expression is regulated by the proinflammatory
      cytokines tumor necrosis factor and interleukin-1, and Sef specifically inhibits
      "classical" NF-kappaB (p50:p65) activation by these ligands. Like IkappaBs, Sef
      sequesters NF-kappaB in the cytoplasm of resting cells. However, contrary to
      IkappaBs, Sef continues to constrain NF-kappaB nuclear entry upon ligand
      stimulation. Accordingly, endogenous Sef knockdown markedly enhances stimulus
      induced NF-kappaB nuclear translocation and consequent activity. This study
      establishes Sef as a feedback antagonist of proinflammatory cytokines and
      highlights its potential to regulate the crosstalk between proinflammatory
      cytokine receptors and receptor tyrosine kinases.

PMID- 22975330
TI  - Wnt signaling regulates postembryonic hypothalamic progenitor differentiation.
AB  - Previous studies have raised the possibility that Wnt signaling may regulate both
      neural progenitor maintenance and neuronal differentiation within a single
      population. Here we investigate the role of Wnt/beta-catenin activity in the
      zebrafish hypothalamus and find that the pathway is first required for the
      proliferation of unspecified hypothalamic progenitors in the embryo. At later
      stages, including adulthood, sequential activation and inhibition of Wnt activity
      is required for the differentiation of neural progenitors and negatively
      regulates radial glia differentiation. The presence of Wnt activity is conserved
      in hypothalamic progenitors of the adult mouse, where it plays a conserved role
      in inhibiting the differentiation of radial glia. This study establishes the
      vertebrate hypothalamus as a model for Wnt-regulated postembryonic neural
      progenitor differentiation and defines specific roles for Wnt signaling in
      neurogenesis.

PMID- 22975331
TI  - Extradenticle and homothorax control adult muscle fiber identity in Drosophila.
AB  - Here we identify a key role for the homeodomain proteins Extradenticle (Exd) and
      Homothorax (Hth) in the specification of muscle fiber fate in Drosophila. exd and
      hth are expressed in the fibrillar indirect flight muscles but not in tubular
      jump muscles, and manipulating exd or hth expression converts one muscle type
      into the other. In the flight muscles, exd and hth are genetically upstream of
      another muscle identity gene, salm, and are direct transcriptional regulators of
      the signature flight muscle structural gene, Actin88F. Exd and Hth also impact
      muscle identity in other somatic muscles of the body by cooperating with Hox
      factors. Because mammalian orthologs of exd and hth also contribute to muscle
      gene regulation, our studies suggest that an evolutionarily conserved genetic
      pathway determines muscle fiber differentiation.

PMID- 22975332
TI  - A multicenter experience evaluating chronic total occlusion crossing with the
      Wildcat catheter (the CONNECT study).
AB  - OBJECTIVE: Percutaneous techniques for crossing femoropopliteal chronic total
      occlusions (CTOs) offer an alternative to bypass surgery in patients deemed to be
      at increased risk due to advanced age or comorbidities. Recent reports document
      good success rates in catheters designed to reconstitute peripherally occluded
      arteries following failed guidewire passage. The Wildcat catheter (Avinger,
      Redwood City, Calif) is a novel device with a rotating distal tip and deployable
      wedges fashioned for channeling a passage through arterial occlusions. This
      report describes the results of a prospective, multicenter, nonrandomized trial
      evaluating the safety and efficacy of the Wildcat device when crossing de novo or
      restenotic femoropopliteal CTOs. METHODS: Between August 2010 and April 2011,
      patients with peripheral arterial disease due to a femoropopliteal CTO>1 cm and
      <=35 cm were evaluated for study enrollment at 15 U.S. sites. During treatment,
      the physician initially attempted to cross the CTO using conventional guidewires
      per protocol; if the guidewire successfully crossed, the patient was considered a
      screen failure and the Wildcat was not deployed. At 30 days, patients were
      reevaluated. The primary efficacy end point was successful crossing of the
      Wildcat into the distal true lumen as confirmed by angiography. Primary safety
      end points included no in-hospital or 30-day major adverse events, no clinically
      significant perforation or embolization, and no grade C or greater dissection.
      Additional data collected included lesion length, degree of calcification, and
      location. RESULTS: Eighty-eight patients were enrolled in the trial. Of these,
      the Wildcat device was used in 84 patients (95%) per protocol. Successful CTO
      crossing was reported and confirmed by independent review in 89% (75/84) of cases
      with 5% (4/84) major adverse events as defined in the protocol (predominantly
      perforations sealed with balloon inflation). There were no clinically relevant
      events associated with any of the perforations. The mean CTO length was 174+/-96
      mm (range, 15-350 mm). Approximately 57% (n=48) of all lesions were categorized
      as containing at least moderate calcification. Eighty-nine percent (n=75) of
      vessels recanalized were superficial femoral arteries. CONCLUSIONS: In this
      multicenter study, the Wildcat catheter demonstrated an 89% crossing success rate
      with little associated morbidity. The Wildcat catheter is a viable device for
      crossing moderately calcified femoropopliteal CTOs.

PMID- 22975333
TI  - Patterns of femoropopliteal recurrence after routine and selective stenting
      endoluminal therapy.
AB  - OBJECTIVE: This study determined the incidence and characteristics of recurrent
      disease after femoropopliteal angioplasty, following either selective or routine
      stenting of diseased site(s). METHODS: Retrospective analysis of a prospectively
      maintained database for femoropopliteal interventions from June 2003 to July 2010
      was performed. Interventions during this period were from a single institution,
      followed up at 1, 3, and 6 months after initial intervention and on a semiannual
      basis thereafter with clinical examinations and duplex ultrasound imaging. Two
      groups were identified: those with routine stenting (RS; routine stenting for all
      diseased areas) and those with selective stenting (SS; selective stenting for
      only segments which exhibited compromised flow from residual stenosis or
      significant dissection). Patients who developed recurrent symptoms (claudication,
      rest pain), a decrease in ankle-brachial index (ABI) (>0.2), or duplex
      documentation of a significant (>80%) recurrent stenosis underwent
      reintervention. Patient demographics, comorbidities, Trans-Atlantic Inter-Society
      Consensus (TASC) II classification, runoff, and degree of calcification (none,
      mild, moderate, severe) at initial intervention were recorded. The time to
      reintervention and recurrence pattern were recorded for both groups. RESULTS:
      During the study period, 746 endovascular interventions in 477 patients were
      performed. Total reintervention rate, including bypass, amputation, and
      asymptomatic occlusion after initial intervention, was 36.48% (group SS, 42.9%;
      group RS, 33.1%; P=.04). Of all initial interventions, 182 endovascular
      reinterventions in 165 patients for recurrent femoropopliteal disease were
      identified (group SS, 70; group RS, 95). No differences were noted among the
      groups in gender, comorbidities, initial TASC II classification, run off,
      calcification scores, or statin or clopidogrel use, or both. Time to recurrence
      was similar in the RS and SS groups. TASC II classification, runoff score, and
      degree of calcification were similar between the two groups. Although not
      statistically significant, analysis of recurrence pattern demonstrated de novo
      stenosis was more common in the SS group (50.0% vs 34.7%; P=.06). CONCLUSIONS:
      This single-center retrospective study found a significant difference in the
      incidence of recurrence requiring reintervention between patients treated with
      selective and routine stenting for femoropopliteal disease. Analysis of
      endovascular reinterventions, however, reveals no significant difference in
      recurrence time or recurrence pattern between the two groups. No significant
      differences were identified in time to recurrence, TASC II classification,
      runoff, and calcification of endovascular reinterventions between the two groups'
      end points. Additional prospective studies to evaluate the roles of routine and
      selective stenting in symptomatic femoropopliteal peripheral arterial disease and
      to investigate recurrence lesion characteristics and the patency of multiple
      endovascular interventions between these two groups are needed.

PMID- 22975334
TI  - Eagle scouting.

PMID- 22975335
TI  - Prognostic value of 12-lead electrocardiogram and peak troponin I level after
      vascular surgery.
AB  - OBJECTIVE: The aim of this investigation was to determine if the presence of
      ischemic electrocardiographic (ECG) changes in patients undergoing vascular
      surgery provides incremental prognostic information about the long-term risk of
      death compared with a single peak troponin level within 48 hours after surgery.
      METHODS: This was a retrospective analysis of 337 patients undergoing moderate
      risk to high-risk vascular surgery at our institution whose ECG and biomarker
      data were complete. Peak cardiac troponin (cTn) I values that exceeded the upper
      reference limit (URL) were categorized as low-positive (+), at or exceeding the
      URL but less than three times the URL, or high-positive (+), at or exceeding
      three times the URL. ECGs were classified as ischemic or nonischemic. The primary
      outcome was death at 1 year after the vascular operation. Independent predictors
      of long-term mortality were determined by Cox proportional hazards regression
      analysis. RESULTS: The most common vascular problem was an expanding abdominal
      aortic aneurysm (n=185 [55%]). With regard to cTnI, 53 patients (16%) were
      classified as high (+) and 82 (24%) as low (+). The ECG in 21 patients (6%)
      showed evidence of myocardial ischemia. An increase in 1-year mortality of 3% for
      normal, 11% for low (+), and 17% for high (+) (P<.01) was seen with incremental
      cTn values. Independent predictors of long-term mortality were age (odds ratio
      [OR], 1.05, 95% confidence interval [CI], 1.02-1.07; P<.01), stratified troponin
      (OR, 1.62; 95% CI, 1.25-2.10; P<.01), tissue loss (OR, 3.30; 95% CI, 1.72-6.33;
      P<.01), stratified Revised Cardiac Risk Index (OR, 1.32; 95% CI, 0.97-1.81;
      P<.07), and statin use (OR, 0.62; 95% CI, 0.40-0.98; P=.04). The presence of
      ischemia on ECG was not a predictor of long-term mortality. CONCLUSIONS: In the
      presence of an elevated cTn I, the ECG is not an independent predictor of long
      term mortality after vascular surgery. These results support a strategy of
      routine surveillance of cTns after vascular surgery for the detection of cardiac
      events and postoperative risk stratification.

PMID- 22975336
TI  - Flow control technique to prevent distal embolization during mechanical
      thrombectomy.
AB  - In an era of increasing emphasis on minimally invasive surgery, distal
      embolization remains a concern in the absence of distal flow control. We present
      a case using an endovascular flow control technique that can be used for reducing
      distal embolic events during endovascular recanalization of aortoiliac occlusive
      disease. This technique has been used in four patients so far (two with native
      anatomy and two with aorto-bi-iliac grafts) with no evidence of angiographic or
      clinical embolic complications.

PMID- 22975337
TI  - Stent misalignment of the Zenith Dissection Endovascular System.
AB  - The Zenith Dissection Endovascular System is a device designed for treatment of
      aortic type B dissection utilizing the Provisional ExTension to Induce COmplete
      ATtachment (PETTICOAT) technique. Due to the stent design (low radial force and
      lack of columnar support), significant risk of stent misalignment exists, which
      we have encountered in four out of 25 patients treated since 2005. Misalignment
      may result from excessive manipulation of the delivery system at the time of
      implantation or during catheter manipulation during adjunctive or secondary
      procedures. The manufacturer has modified the design of this device in order to
      prevent misalignment, although no serious clinical consequences of this
      misalignment have been reported with a mean follow-up of 50 months. Care with
      catheter manipulation after device deployment and accurate review of
      postoperative imaging are still warranted.

PMID- 22975338
TI  - Aneurysm-osteoarthritis syndrome with visceral and iliac artery aneurysms.
AB  - OBJECTIVE: Aneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is
      a recently described autosomal-dominant syndrome characterized by arterial
      aneurysms, tortuosity, and aortic dissections in combination with osteoarthritis.
      Our objective was to evaluate the AOS-related vascular consequences in the
      visceral and iliac arteries and raise awareness for this aggressive syndrome
      among vascular specialists. METHODS: All AOS patients were monitored regularly
      according to our clinical AOS protocol. The study included those with one or more
      visceral aneurysms or tortuosity, or both. Clinical and surgical data were
      obtained from record abstraction. RESULTS: The study included 17 AOS patients
      (47% men) aged 47+/-13 years. A total of 73 aneurysms were encountered, of which
      46 were located in the abdomen. The common iliac artery was most commonly
      affected (37%), followed by the superior mesenteric artery (15%), celiac trunk
      (11%), and splenic artery (9%). Rapid aneurysm growth<=1 year was found in three
      arteries (gastric, hepatic, and vertebral artery). Furthermore, arterial
      tortuosity was noted in 94% of patients. Four patients underwent six elective
      (endo) vascular interventions for aneurysms in the iliac, hepatic, gastric, or
      splenic artery, without major perioperative or postoperative complications.
      CONCLUSIONS: AOS predisposes patients to widespread visceral and iliac artery
      aneurysms and extreme arterial tortuosity. Early elective aneurysm repair should
      be considered because the risk of aneurysm rupture is estimated to be very high
      and elective (endo) vascular interventions were not complicated by fragility of
      arterial tissue. Given the aggressive behavior of AOS, it is of utmost importance
      that vascular specialists are aware of this new syndrome.

PMID- 22975339
TI  - Dengue vaccine development: a 75% solution?

PMID- 22975340
TI  - Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue
      vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial.
AB  - BACKGROUND: Roughly half the world's population live in dengue-endemic countries,
      but no vaccine is licensed. We investigated the efficacy of a recombinant, live,
      attenuated tetravalent dengue vaccine. METHODS: In this observer-masked,
      randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy
      Thai schoolchildren aged 4-11 years were randomly assigned (2:1) to receive three
      injections of dengue vaccine or control (rabies vaccine or placebo) at months 0,
      6, and 12. Randomisation was by computer-generated permuted blocks of six and
      participants were assigned with an interactive response system. Participants were
      actively followed up until month 25. All acute febrile illnesses were
      investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non
      structural protein 1 ELISA. The primary objective was to assess protective
      efficacy against virologically confirmed, symptomatic dengue, irrespective of
      severity or serotype, occurring 1 month or longer after the third injection (per
      protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530.
      FINDINGS: 4002 participants were assigned to vaccine (n=2669) or control
      (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221
      control). 134 cases of virologically confirmed dengue occurred during the study.
      Efficacy was 30.2% (95% CI -13.4 to 56.6), and differed by serotype. Dengue
      vaccine was well tolerated, with no safety signals after 2 years of follow-up
      after the first dose. INTERPRETATION: These data show for the first time that a
      safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in
      various epidemiological settings will provide pivotal data for the CYD dengue
      vaccine candidate. FUNDING: Sanofi Pasteur.

PMID- 22975341
TI  - A novel variant of the RON receptor tyrosine kinase derived from colorectal
      carcinoma cells which lacks tyrosine phosphorylation but induces cell migration.
AB  - Generation of splice variants in the RON receptor tyrosine kinase facilitates the
      invasive phenotype of colorectal cancers. Here, we report a new splice variant of
      RON in the human colorectal cancer cell line HCT116. This variant is encoded by a
      transcript differing from the full-length RON mRNA by an in-frame deletion of 106
      amino acids in the extracellular domain of RON beta-chain. The deleted transcript
      originates by an alternative deletion of exon 2 and exon 3. The molecular weight
      of this variant is 160 kDa. Thus, we named this variant RONDelta160(E2E3). This
      variant is a single-chain protein and expressed in the intracellular compartment.
      We found that RONDelta160(E2E3) had no tyrosine phosphorylation ability, but it
      has constitutively activated Akt activity in transfected HEK293 epithelial cells.
      The expression of this variant in HEK293 cells resulted in an increased migratory
      activity in vitro mediated through the PI-3K/Akt pathway. Our data describes a
      new splice variant of RON and suggests a novel role for the RON receptor in the
      progression of metastasis in colorectal cancer.

PMID- 22975343
TI  - Alpha-1-antitrypsin inhibits nitric oxide production.
AB  - NO is an endogenously produced gas that regulates inflammation, vascular tone,
      neurotransmission, and immunity. NO production can be increased by exposing cells
      to several endogenous and exogenous proinflammatory mediators, including IFN
      gamma, TNF-alpha, IL-1beta, and LPS. As AAT has been shown to inhibit cell
      activation and suppress cytokine production associated with proinflammatory
      stimulation, we examined AAT for NO-suppressive function. In RAW 264.7 murine
      macrophagic cells, physiological AAT concentrations significantly inhibited
      combined LPS- and IFN-gamma-induced NO synthesis, and NO synthesis inhibition was
      associated with decreased expression of iNOS, suppressed NF-kappaB activation,
      and reduced translocation of extracellular AAT into the interior of RAW 264.7
      cells. CE-2072, a synthetic inhibitor of serine proteases, also suppressed NO
      production, iNOS expression, and NF-kappaB activation. However, AAT did not alter
      activation of intracellular MAPKs. In subjects with genetic AAT deficiency,
      exhaled NO was increased significantly compared with exhaled NO in healthy
      controls. These in vitro and in vivo studies suggest that AAT is an endogenous
      inhibitor of NO production. Administering AAT or AAT-like molecules may have use
      as a treatment for diseases associated with excessive NO production.

PMID- 22975345
TI  - Total internal reflection fluorescence imaging of Ca(2+)-induced Ca(2+) release
      in mouse urinary bladder smooth muscle cells.
AB  - In smooth muscles (SMs), cytosolic Ca(2+) ([Ca(2+)](cyt)) dynamics during an
      action potential are triggered by Ca(2+) influx through voltage-dependent Ca(2+)
      channels (VDCCs) in the plasma membrane. The physiological significance of Ca(2+)
      amplification by subsequent Ca(2+) release through ryanodine receptors (RyRs)
      from the sarcoplasmic reticulum (SR) is still a matter of topics in SMs. In the
      present study, depolarization-evoked local Ca(2+) dynamics in Ca(2+) microdomain
      were imaged using total internal reflection fluorescence (TIRF) microscopy in
      mouse urinary bladder SM cells (UBSMCs). Upon depolarization under whole-cell
      voltage-clamp, the rapid and local elevation of [Ca(2+)](cyt) was followed by
      larger [Ca(2+)](cyt) increase with propagation occurred in a limited TIRF zone
      within ~200nm from cell surface. The depolarization-evoked [Ca(2+)](cyt) increase
      in a TIRF zone was abolished or greatly reduced by the pretreatment with Cd(2+)
      or ryanodine, respectively. The initial local [Ca(2+)](cyt) increases were
      mediated by Ca(2+) influx through single or clustered VDCCs as Ca(2+) sparklets,
      and the following step was elicited by Ca(2+)-induced Ca(2+) release (CICR)
      through RyR from SR. The depolarization-induced outward currents, mainly due to
      large-conductance Ca(2+)-activated K(+) channel activation, were also markedly
      reduced by Cd(2+) and ryanodine. In addition, TIRF analyses showed that the
      fluorescent signals of individual or clustered VDCC distributed in relatively
      uniform fashion and that a subset of RyRs in the subplasmalemmal SR also located
      in TIRF zone. In conclusion, fast TIRF imaging successfully demonstrated two step
      Ca(2+) events upon depolarization in Ca(2+) microdomain of UBSMCs; the initial
      Ca(2+) influx as Ca(2+) sparklets through discrete VDCC or their clusters and the
      following CICR via the activation of loosely coupled RyRs in SR located in the
      Ca(2+) microdomains.

PMID- 22975344
TI  - The French noun phrase in preschool children with SLI: morphosyntactic and error
      analyses.
AB  - We studied spontaneous speech noun-phrase production in eight French-speaking
      children with SLI (aged 5 ; 0 to 5 ; 11) and controls matched on age (4 ; 10 to 5
      ; 11) or MLU (aged 3 ; 2 to 4 ; 1). Results showed that children with SLI prefer
      simple DP structures to complex ones while producing more substitution and
      omission errors than controls. The three groups also showed distinct error
      patterns. Children with SLI appeared to have difficulty with phonological
      processes involved in liaison, elision, and contraction, whereas control children
      tended to make more lexical errors. These data support models of reduced
      morphosyntactic and syntactic abilities in this population, and suggest that
      morphophonological processes should also be integrated into descriptive models of
      SLI.

PMID- 22975346
TI  - Membrane topology of Salmonella invasion protein SipB confers osmotolerance.
AB  - Salmonella enterica serovar Typhimurium is a major cause of human
      gastrointestinal illness worldwide. This pathogen can persist in a wide range of
      environments, making it of great concern to public health. Here, we report that
      the salmonella pathogenicity island (SPI)-1 effector protein SipB exhibits a
      membrane topology that confers bacterial osmotolerance. Disruption of the sipB
      gene or the invG gene (SPI-1 component) significantly reduced the osmotolerance
      of S. Typhimurium LT2. Biochemical assays showed that NaCl osmolarity increased
      the membrane topology of SipB, and a neutralising antibody against SipB reduced
      osmotolerance in the WT strain. The WT strain, but not the sipB mutant, exhibited
      elevated cyclopropane fatty acid C19:0 during conditions of osmotic stress,
      correlating with the observed levels of survival and membrane integrity. This
      result suggests a link between SipB and the altered fatty acid composition
      induced upon exposure to osmotic stress. Overall, our findings provide the first
      evidence that the Salmonella virulence translocon SipB affects membrane fluidity
      and alters bacterial osmotolerance.

PMID- 22975347
TI  - Co-culture with Sertoli cells promotes proliferation and migration of umbilical
      cord mesenchymal stem cells.
AB  - Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in
      transplant therapy. The proliferation and migration of MSCs are the determinants
      of the efficiency of MSC transplant therapy. Sertoli cells are a kind of "nurse"
      cells that support the development of sperm cells. Recent studies show that
      Sertoli cells promote proliferation of endothelial cells and neural stem cells in
      co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also
      promote proliferation and migration of UCMSCs. To examine this hypothesis, we
      isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co
      cultured them using a Transwell system. We found that UCMSCs exhibited strong
      proliferation ability and potential to differentiate to other cell lineages such
      as osteocytes and adipocytes. The presence of Sertoli cells in co-culture
      significantly enhanced the proliferation and migration potential of UCMSCs
      (P<0.01). Moreover, these phenotypic changes were accompanied with upregulation
      of multiple genes involved in cell proliferation and migration including phospho
      Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK
      and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC
      proliferation and migration potential.

PMID- 22975348
TI  - ERalpha positively regulated DNMT1 expression by binding to the gene promoter
      region in human breast cancer MCF-7 cells.
AB  - Estrogen receptors (ER) are expressed in approximately 65% of human breast
      cancer. Clinical trials and retrospective analyses showed that ER-positive (ER+)
      tumors were more vulnerable to development of chemotherapy resistance than ER
      negative (ER-) tumors. The underlying mechanism is still to be elucidated.
      Aberrant DNA methylation has been recognized to be associated with cancer
      chemotherapy resistance. Recently, steroid hormone and their receptors have been
      found to be involved in the regulation of methyltransferases (DNMTs) and thereby
      contribute to chemotherapy resistance. The purpose of this study is to explore
      whether ERalpha could directly regulate the DNMTs expression. We first analyzed
      the methylation alterations and its correlation with the expression levels of
      three types of DNMTs in our established paclitaxel-resistant breast cancer lines,
      MCF-7(ER+)/PTX and MDA-MB-231(ER-)/PTX cell lines, using qMSP, real-time PCR and
      Western blot. Then we determined the function of ERalpha in regulation of DNMT1
      using luciferase report gene systems. Our data demonstrated for the first time
      that ERalpha could upregulate DNMT1 expression by directly binding to the DNMT1
      promoter region in MFC-7(ER+)/PTX cells.

PMID- 22975349
TI  - Prolyl hydroxylase domain protein 2 regulates the intracellular cyclic AMP level
      in cardiomyocytes through its interaction with phosphodiesterase 4D.
AB  - Cyclic adenosine 3',5'-monophosphate (cAMP), which is synthesized by adenylyl
      cyclase (AC) and degraded by phosphodiesterase (PDE), plays crucial roles in the
      regulation of multiple cellular functions and physiological processes. Prolyl
      hydroxylase domain (PHD) proteins, which belong to a family of dioxygenases that
      function as oxygen sensors through their hydroxylation activity, have been
      implicated in multiple signaling pathways. Here, we aimed to determine whether
      PHD played a role in regulating intracellular cAMP level in cardiomyocytes.
      Through the overexpression/knockdown of the PHD gene and the measurement of the
      cAMP content, we found that PHD2, but not PHD1 or PHD3, acts as a regulator of
      intracellular cAMP. In neonatal rat cardiomyocytes and H9c2 cells, the
      overexpression of PHD2 increased the intracellular cAMP level, whereas the PHD2
      knockdown reduced it. There was no alteration in the AC expression or activity in
      cells that overexpressed or downregulated PHD2. The overexpression of PHD2
      decreased both the protein expression and the activity of phosphodiesterase 4D
      (PDE4D), whereas the PHD2 knockdown increased the PDE4D expression and activity.
      Co-immunoprecipitation experiments revealed a direct binding between PHD2 and
      PDE4D and liquid chromatography-tandem mass spectrometry analyses identified the
      specific hydroxylation sites on PDE4D. In conclusion, PHD2 may directly interact
      with PDE4D to function as a novel regulator of the intracellular cAMP levels in
      cardiomyocytes.

PMID- 22975350
TI  - Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast
      cancer cells by targeting heat shock proteins.
AB  - Heat shock proteins (HSPs) are involved in protein folding, aggregation,
      transport and/or stabilization by acting as a molecular chaperone, leading to
      inhibition of apoptosis by both caspase dependent and/or independent pathways.
      HSPs are overexpressed in a wide range of human cancers and are implicated in
      tumor cell proliferation, differentiation, invasion and metastasis. HSPs
      particularly 27, 70, 90 and the transcription factor heat shock factor1 (HSF1)
      play key roles in the etiology of breast cancer and can be considered as
      potential therapeutic target. The present study was designed to investigate the
      role of sulphoraphane, a natural isothiocyanate on HSPs (27, 70, 90) and HSF1 in
      two different breast cancer cell lines MCF-7 and MDA-MB-231 cells expressing wild
      type and mutated p53 respectively, vis-a-vis in normal breast epithelial cell
      line MCF-12F. It was furthermore investigated whether modulation of HSPs and HSF1
      could induce apoptosis in these cells by altering the expressions of p53, p21 and
      some apoptotic proteins like Bcl-2, Bax, Bid, Bad, Apaf-1 and AIF. Sulphoraphane
      was found to down-regulate the expressions of HSP70, 90 and HSF1, though the
      effect on HSP27 was not pronounced. Consequences of HSP inhibition was
      upregulation of p21 irrespective of p53 status. Bax, Bad, Apaf-1, AIF were
      upregulated followed by down-regulation of Bcl-2 and this effect was prominent in
      MCF-7 than in MDA-MB-231. However, very little change in the expression of Bid
      was observed. Alteration in Bcl-2 Bax ratio resulted in the release of cytochrome
      c from mitochondria and activation of caspases 3 and 9 which are in agreement
      with apoptotic index values. Sulphoraphane therefore can be regarded as a potent
      inducer of apoptosis due to HSP modulation in breast cancer cells.

PMID- 22975351
TI  - Drought-induced activation and rehydration-induced inactivation of MPK6 in
      Arabidopsis.
AB  - Mitogen-activated protein kinases (MPKs) have roles in regulating developmental
      processes and responses to various stimuli in plants. Activations of some MPKs
      are necessary for proper responses to hyperosmolarity and to a stress-related
      phytohormone, abscisic acid (ABA). However, there is no direct evidence that MPK
      activations are regulated by drought and rehydration. Here we show that the
      activation state of one of the Arabidopsis MPKs, MPK6, is directly regulated by
      drought and rehydration. An immunoblot analysis using an anti-active MPK antibody
      detected drought-induced activation and rehydration-induced inactivation of MPK6.
      MPK6 was activated by drought even in an ABA-deficient mutant, aba2-4. In
      addition, exogenously added ABA failed to suppress the rehydration-dependent
      inactivation of MPK6. Under drought conditions, elevated levels of reactive
      oxygen species (ROS), which are known elicitors of MPK6 activation, were detected
      in both wild type and an MPK6-deficient mutant, mpk6-4. These results suggest
      that ROS, but not ABA, induces MPK6 activation as an upstream signal under
      drought conditions.

PMID- 22975352
TI  - Alteration of the mode of antibacterial action of a defensin by the amino
      terminal loop substitution.
AB  - Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs)
      are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt
      a conserved cysteine-stabilized alpha-helical and beta-sheet (CSalphabeta) fold
      with a different amino-terminal loop (n-loop) size and diverse modes of
      antibacterial action. Although they both are identified as inhibitors of cell
      wall biosynthesis, only CITDs evolved membrane disruptive ability by peptide
      oligomerization to form pores. To understand how this occurred, we modified
      micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by
      substituting its n-loop with that of an insect-derived CITDs. After air
      oxidization, the synthetic hybrid defensin (termed Al-M) was structurally
      identified by circular dichroism (CD) and functionally evaluated by antibacterial
      and membrane permeability assays and electronic microscopic observation. Results
      showed that Al-M folded into a native-like defensin structure, as determined by
      its CD spectrum that is similar to that of micasin. Al-M was highly efficacious
      against the Gram-positive bacterium Bacillus megaterium with a lethal
      concentration of 1.76MUM. As expected, in contrast to micasin, Al-M killed the
      bacteria through a membrane disruptive mechanism of action. The alteration in
      modes of action supports a key role of the n-loop extension in assembling
      functional surface of CITDs for membrane disruption. Our work provides mechanical
      evidence for evolutionary relationship between AITDs and CITDs.

PMID- 22975353
TI  - Heat induces gene amplification in cancer cells.
AB  - BACKGROUND: Hyperthermia plays an important role in cancer therapy. However, as
      with radiation, it can cause DNA damage and therefore genetic instability. We
      studied whether hyperthermia can induce gene amplification in cancer cells and
      explored potential underlying molecular mechanisms. MATERIALS AND METHODS: (1)
      Hyperthermia: HCT116 colon cancer cells received water-submerged heating
      treatment at 42 or 44 degrees C for 30 min; (2) gene amplification assay using N
      (phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate
      transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern
      blotting for confirmation of increased cad gene copies in PALA-resistant cells;
      (4) gammaH2AX immunostaining to detect gammaH2AX foci as an indication for DNA
      double strand breaks. RESULTS: (1) Heat exposure at 42 or 44 degrees C for 30 min
      induces gene amplification. The frequency of cad gene amplification increased by
      2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 degrees C for
      30 min induces DNA double strand breaks in HCT116 cells as shown by gammaH2AX
      immunostaining. CONCLUSION: This study shows that heat exposure can induce gene
      amplification in cancer cells, likely through the generation of DNA double strand
      breaks, which are believed to be required for the initiation of gene
      amplification. This process may be promoted by heat when cellular proteins that
      are responsible for checkpoints, DNA replication, DNA repair and telomere
      functions are denatured. To our knowledge, this is the first study to provide
      direct evidence of hyperthermia induced gene amplification.

PMID- 22975354
TI  - Role of ferritin in the cytodifferentiation of periodontal ligament cells.
AB  - This study investigated the expression and functions of ferritin, which is
      involved in osteoblastogenesis, in the periodontal ligament (PDL). The PDL is one
      of the most important tissues for maintaining the homeostasis of teeth and tooth
      supporting tissues. Real-time PCR analyses of the human PDL revealed abundant
      expression of ferritin light polypeptide (FTL) and ferritin heavy polypeptide
      (FTH), which encode the highly-conserved iron storage protein, ferritin.
      Immunohistochemical staining demonstrated predominant expression of FTL and FTH
      in mouse PDL tissues in vivo. In in vitro-maintained mouse PDL cells, FTL and FTH
      expressions were upregulated at both the mRNA and protein levels during the
      course of cytodifferentiation and mineralization. Interestingly, stimulation of
      PDL cells with exogenous apoferritin (iron-free ferritin) increased calcified
      nodule formation and alkaline phosphatase activity as well as the mRNA
      expressions of mineralization-related genes during the course of
      cytodifferentiation. On the other hand, RNA interference of FTH inhibited the
      mineralized nodule formation of PDL cells. This is the first report to
      demonstrate that ferritin is predominantly expressed in PDL tissues and
      positively regulates the cytodifferentiation and mineralization of PDL cells.

PMID- 22975355
TI  - Molecular mechanism of hydrophobic charge-induction chromatography: interactions
      between the immobilized 4-mercaptoethyl-pyridine ligand and IgG.
AB  - Hydrophobic charge-induction chromatography (HCIC) is a novel bioseparation
      technology, especially for antibody purification. In order to better understand
      the molecular mechanism of HCIC, the typical ligand of 4-mercaptoethyl-pyridine
      (MEP) was coupled onto the cellulose matrix, and the binding and departing of IgG
      were studied with the molecular dynamics simulation. Based on the previous work
      with free MEP ligand (J. Phys. Chem. B, 116 (4) (2012) 1393-1400), the pocket
      around TYR319 and LEU309 on the CH2 domain of IgG was selected as the potential
      binding site for the Fc fragment of IgG (Fc-A), and the complex of matrix-ligand
      Fc-A was formed for the molecular simulation. Both single ligand and ligand net
      were investigated in the present work. It was found that the MEP ligand
      immobilized on the cellulose matrix could capture the Fc-A at neutral pH during
      the simulation, and the Fc-A would depart quickly when pH was changed to 4.0. The
      hydrophobic interactions and hydrogen bonds controlled the binding of Fc-A on the
      immobilized ligands at neutral pH and the electrostatic repulsion caused the
      departing of Fc-A at acid condition. For the ligand net, multipoint binding was
      found, while one ligand dominated the binding of Fc-A and other ligands might
      enhance the adsorption of protein. In addition, the adsorption isotherm and the
      isothermal titration calorimetry (ITC) were used to evaluate the molecular
      interactions. The experimental results indicated that the hydrophobic interaction
      is the major driving force for the adsorption of IgG on the MEP resin, which was
      in good agreement with those findings of molecular simulation. The molecular
      simulation and thermodynamic results verified strongly the molecular mechanism of
      HCIC--the hydrophobic interactions for binding and the charge-induction repulsion
      for elution. Better understanding on the molecular interactions would be
      beneficial to design new HCIC ligands for improving the efficiency of antibody
      separation.

PMID- 22975356
TI  - The development of a sheathless capillary electrophoresis electrospray ionization
      mass spectrometry interface based on thin conducting liquid film.
AB  - A simple two column sheathless CE/MS interface was constructed using
      polydimethylsiloxane to fabricate a microdevice allowing facile column alignment
      and electrical connection. One conducting reservoir, two holes and one 1mm length
      microchannel between the holes were fabricated on the microdevice. The two holes
      were used for connecting separation capillary and ESI sprayer. The hole for ESI
      sprayer was fabricated at the edge of the conducting reservoir. The ESI sprayer
      was inserted through the reservoir to the hole so allowing it to be aligned with
      the separation column. Because the size of the hole was fabricated slightly
      larger than the outer diameter of the ESI sprayer, the electrical conduction was
      established through the thin conductive liquid film formed in the space between
      the ESI sprayer and the hole. The interface design presented was both easy to
      fabricate and operate and demonstrated good performance. The dead volume did not
      significantly affect operation as indicated by a demonstrated preservation of
      separation resolution. The intra-day precision and inter-day precision for peak
      areas and migration times observed using this interface were found to be less
      than 12% and 5%, respectively.

PMID- 22975357
TI  - Principles for designing ordered protein assemblies.
AB  - In nature, many proteins have evolved to have self-complementary shapes. This
      drives them to assemble into supramolecular structures, sometimes of great
      complexity, and often carrying out sophisticated cellular functions. Designing
      novel proteins that can self-assemble into similarly complex structures is a
      longstanding goal in bioengineering. New ideas, combined with continually
      improving computer algorithms, are making it possible to advance on that goal,
      bringing wide-ranging applications in synthetic biology within reach. Prospective
      applications range from vaccine design to molecular delivery to bioactive
      materials. Recent strategies and examples of successfully designed protein cages,
      layers, and crystals are reviewed.

PMID- 22975358
TI  - Ultra-fast electron diffraction at surfaces: from nanoscale heat transport to
      driven phase transitions.
AB  - Many fundamental processes of structural changes at surfaces occur on a pico- or
      femtosecond time scale. In order to study such ultra-fast processes, we have
      combined modern surface science techniques with fs-laser pulses in a pump-probe
      scheme. Reflection high energy electron diffraction (RHEED) with grazing incident
      electrons ensures surface sensitivity for the probing electron pulses. Utilizing
      the Debye-Waller effect, we studied the cooling of vibrational excitations in
      monolayer adsorbate systems or the nanoscale heat transport from an ultra-thin
      film through a hetero-interface on the lower ps-time scale. The relaxation
      dynamics of a driven phase transition far away from thermal equilibrium is
      demonstrated with the In-induced (8*2) reconstruction on Si(111). This surface
      exhibits a Peierls-like phase transition at 100K from a (8*2) ground state to
      (4*1) excited state. Upon excitation by a fs-laser pulse, this structural phase
      transition is driven into an excited (4*1) state at a sample temperature of 20K.
      Relaxation into the (8*2) ground state occurs after more than 150 ps.

PMID- 22975361
TI  - Comparison of FDG whole-body PET/CT and gadolinium-enhanced whole-body MRI for
      distant malignancies in patients with malignant tumors: a meta-analysis.
AB  - BACKGROUND: We performed a meta-analysis to compare the performance of whole-body
      positron emission tomography/computed tomography (WB-PET/CT) with that of whole
      body magnetic resonance imaging (WB-MRI) for the overall assessment of distant
      malignancies in patients with malignant tumors. METHODS: We performed a meta
      analysis of 13 available articles (1239 patients). We calculated sensitivities,
      specificities, positive likelihood ratios, and negative likelihood ratios, and
      constructed summary receiver operating characteristic curves using bivariate
      regression models for WB-PET/CT and WB-MRI, respectively. RESULTS: Across nine
      studies (1070 patients), WB-PET/CT have similar patient-based sensitivity (0.85
      versus 0.85) and specificity (0.96 versus 0.97) with WB-MRI. Across 5 studies
      (210 patients), WB-PET/CT have similar lesion-based sensitivity (0.85 vs 0.88)
      and specificity (0.90 vs 0.89) with WB-MRI. Across four studies (511 patients),
      the combined use may have higher patient-based sensitivity (0.89) than WB-PET/CT
      (0.82) and WB-MRI (0.81) alone. CONCLUSION: Both WB-PET/CT and WB-MRI have good
      diagnostic performance for the overall assessment of distant malignancies in
      patients with malignant tumors. The combined use may provide more added value
      than WB-PET/CT and WB-MRI alone.

PMID- 22975359
TI  - NS-398 reverses hypotension in endotoxemic rats: contribution of eicosanoids, NO,
      and peroxynitrite.
AB  - We have previously demonstrated that inhibition of vasodilator prostanoids, PGI2
      and PGE2, and nitric oxide (NO) synthesis by a selective cyclooxygenase-2 (COX-2)
      inhibitor, NS-398, restores blood pressure as a result of increased systemic and
      renal levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in endotoxemic rats.
      The aim of this study was to further investigate the effects of NS-398 on the
      changes in expression and/or activity of COX-2, cytochrome P450 4A1 (CYP4A1),
      inducible NO synthase (iNOS), and peroxynitrite formation in serum, renal,
      cardiac, and/or vascular tissues of lipopolysaccharide (LPS)-treated rats. LPS
      (10mg/kg, i.p.)-induced decrease in blood pressure was associated with increased
      protein levels of COX-2, iNOS, and nitrotyrosine in kidney, heart, thoracic
      aorta, and superior mesenteric artery. The activities of COX-2 and iNOS as well
      as levels of PGI2, PGE2, and nitrotyrosine were also increased in the systemic
      circulation and renal, cardiac, and vascular tissues of LPS-treated rats. In
      contrast, renal, cardiac, and vascular CYP4A1 protein expression as well as
      systemic and tissue levels of 20-HETE were decreased in endotoxemic rats. These
      effects of LPS, except COX-2 protein expression, were prevented by NS-398 (10
      mg/kg, i.p.), given 1h after injection of LPS. These data suggest that COX-2
      derived vasodilator prostanoids, PGI2 and PGE2, produced during endotoxemia
      increase iNOS protein expression and activity as well as peroxynitrite formation
      resulting in decreased CYP4A1 protein expression and 20-HETE synthesis. Taken
      together, we concluded that an increase in 20-HETE levels associated with a
      decrease in the production of vasodilator prostanoids and NO participates in the
      effect of NS-398 to prevent hypotension in the rat model of septic shock.

PMID- 22975362
TI  - Risk of second primary malignancies in women with cervical cancer: a population
      based study in Taiwan over a 30-year period.
AB  - OBJECTIVE: Studies conducted in Western countries have reported an increased risk
      for second primary malignancies after cervical cancer. There is little
      documentation of ethnic differences in this increased risk, and most of the Asian
      studies are hospital-based studies with small case numbers. METHODS: Using
      population-based data from the Taiwan Cancer Registry for the period 1979-2008,
      we quantified standardized incidence ratios (SIRs) among 52,972 women with
      initial diagnoses of cervical cancer. RESULTS: Among the 52,972 women, 3061
      (5.78%) developed second primary cancers during 433,571 person-years of follow
      up. Overall, the SIR for developing a subsequent second cancer was significantly
      greater than that of the general population (1.36 [95% CI, 1.32-1.41]). There was
      a greater risk for cancers of the esophagus, stomach, small intestine, rectum,
      lung, bone, non-melanoma skin, uterine corpus, vagina/vulva, bladder, kidney, and
      leukemia. When further examining age at diagnosis of cervical cancer (<50 and
      >=50) for these 12 sites, we found that the risk of second cancers (SIR, <50 and
      >=50: 3.08 vs. 1.63) was higher not only in younger patients, except for non
      melanoma skin cancer and endometrial cancer, but also within the first 5 years
      after diagnosis of cervical cancer. The median overall survival for women with
      cervical cancer was 18.58 years. The second cancers had a negative impact on
      overall survival after adjusting for age (P<0.001). CONCLUSIONS: SIR for second
      cancers was significantly greater than the general population in cervical cancer
      patients. A young age at the diagnosis of cervical cancer predicted an increased
      risk. The second cancers worsened overall survival.

PMID- 22975360
TI  - Instrumentation for studies of cochlear mechanics: from von Bekesy forward.
AB  - Georg von Bekesy designed the instruments needed for his research. He also
      created physical models of the cochlea allowing him to manipulate the parameters
      (such as volume elasticity) that could be involved in controlling traveling
      waves. This review is about the specific devices that he used to study the motion
      of the basilar membrane thus allowing the analysis that lead to his Nobel Prize
      Award. The review moves forward in time mentioning the subsequent use of von
      Bekesy's methods and later technologies important for motion studies of the organ
      of Corti. Some of the seminal findings and the controversies of cochlear
      mechanics are mentioned in relation to the technical developments.

PMID- 22975364
TI  - The adenosine triphosphate test is a rapid and reliable audit tool to assess
      manual cleaning adequacy of flexible endoscope channels.
AB  - BACKGROUND: The study objective was to verify that the adenosine triphosphate
      (ATP) benchmark of <200 relative light units (RLUs) was achievable in a busy
      endoscopy clinic that followed the manufacturer's manual cleaning instructions.
      METHODS: All channels from patient-used colonoscopes (20) and duodenoscopes (20)
      in a tertiary care hospital endoscopy clinic were sampled after manual cleaning
      and tested for residual ATP. The ATP test benchmark for adequate manual cleaning
      was set at <200 RLUs. The benchmark for protein was <6.4 MUg/cm(2), and, for
      bioburden, it was <4-log10 colony-forming units/cm(2). RESULTS: Our data
      demonstrated that 96% (115/120) of channels from 20 colonoscopes and 20
      duodenoscopes evaluated met the ATP benchmark of <200 RLUs. The 5 channels that
      exceeded 200 RLUs were all elevator guide-wire channels. All 120 of the manually
      cleaned endoscopes tested had protein and bioburden levels that were compliant
      with accepted benchmarks for manual cleaning for suction-biopsy, air-water, and
      auxiliary water channels. CONCLUSION: Our data confirmed that, by following the
      endoscope manufacturer's manual cleaning recommendations, 96% of channels in
      gastrointestinal endoscopes would have <200 RLUs for the ATP test kit evaluated
      and would meet the accepted clean benchmarks for protein and bioburden.

PMID- 22975365
TI  - Factor complexity of crash occurrence: An empirical demonstration using boosted
      regression trees.
AB  - Factor complexity is a characteristic of traffic crashes. This paper proposes a
      novel method, namely boosted regression trees (BRT), to investigate the complex
      and nonlinear relationships in high-variance traffic crash data. The Taiwanese
      2004-2005 single-vehicle motorcycle crash data are used to demonstrate the
      utility of BRT. Traditional logistic regression and classification and regression
      tree (CART) models are also used to compare their estimation results and external
      validities. Both the in-sample cross-validation and out-of-sample validation
      results show that an increase in tree complexity provides improved, although
      declining, classification performance, indicating a limited factor complexity of
      single-vehicle motorcycle crashes. The effects of crucial variables including
      geographical, time, and sociodemographic factors explain some fatal crashes.
      Relatively unique fatal crashes are better approximated by interactive terms,
      especially combinations of behavioral factors. BRT models generally provide
      improved transferability than conventional logistic regression and CART models.
      This study also discusses the implications of the results for devising safety
      policies. 

PMID- 22975366
TI  - Emotional reactions to cycle helmet use.
AB  - It has been suggested that the safety benefits of bicycle helmets are limited by
      risk compensation. The current article tests if previous helmet use influences
      the response to helmets as a safety intervention. This was investigated in a
      field experiment where pace and psychophysiological load were measured. We found
      that after having removed their helmets, routine helmet users cycled more slowly
      and demonstrated increased psychophysiological load. However, for non-users there
      was no significant change in either cycling behaviour or psychophysiological
      load. We discuss the implications of these results for a hypothesis of risk
      compensation in response to helmet use. We also show that heart rate variability
      is a promising measure of psychophysiological load in real-world cycling, at
      least in situations where there is limited physical demand.

PMID- 22975367
TI  - Attentional differences in driving judgments for country and city scenes:
      Semantic congruency in inattentional blindness.
AB  - 'Looked-but-failed-to-see' vehicle collisions occur when a driver gives all
      indications of having responsibly evaluated the driving situation yet still fails
      to see a hazard that is clearly in view. The experience maps well onto the
      psychological phenomenon called inattentional blindness (IB). IB occurs when a
      viewer fails to see an unexpected object that is clearly visible, particularly if
      they are concentrating on an additional primary task. In this study, a driving
      related IB task was used to explore whether an unexpected stimulus (US) such as a
      pedestrian or animal, is more likely to be seen in country or city-related
      driving scenarios if it is congruent or incongruent with the semantic context of
      the scenes, and thus congruent or incongruent with the attentional set of the
      viewer. Overall, participants were more likely to see the US in the City
      scenarios, which also demonstrated a borderline effect of congruency, with
      incongruent stimuli less likely to be seen than congruent stimuli. Analyses
      suggested that driver experience was related to detection of the US in City
      scenarios but not Country scenarios. However, analyses also revealed that
      participants generally tended to drive in city rather than country environments,
      thus prompting speculation that the results may reflect attentional requirements
      for familiar and unfamiliar driving scenarios. Thus we suggest that the analysis
      of the driving situation, and the attentional set that we develop to filter
      information, change when the driving situation is more familiar.

PMID- 22975368
TI  - Transforming the microenvironment: a trick of the metastatic cancer cell.
AB  - Creating a permissive microenvironment is a strategy employed by tumor cells to
      disseminate. In this issue of Cancer Cell, Yang et al. identify the molecular
      signaling events that connect hepatitis infection with TGFbeta activity and T
      regulatory cell recruitment to establish a favorable microenvironment for tumor
      metastasis.

PMID- 22975369
TI  - Ready, set, go: the EGF receptor at the pancreatic cancer starting line.
AB  - Acinar-to-ductal metaplasia (ADM) results from pancreatic injury or KRAS
      activation, and is an early step in pancreatic cancer progression. In this issue
      of Cancer Cell, Ardito and colleagues and Navas and colleagues demonstrate that
      ADM- and KRAS-driven pancreatic cancer require EGFR signaling, revealing a
      mechanism for developmental reprogramming that primes tumorigenesis.

PMID- 22975370
TI  - Strategies for p53 reactivation in human sarcoma.
AB  - Emerging strategies in cancer therapeutics link the genomic mutational and
      proteomic landscape, allowing intelligent reasoning on target selection. In this
      issue of Cancer Cell, Piccinin and colleagues use this approach to demonstrate
      that the mesenchymal protein Twist1 inhibits p53, providing a novel target for
      reactivation of p53 in human sarcoma.

PMID- 22975371
TI  - IDH1 mutations disrupt blood, brain, and barriers.
AB  - The first two murine models of IDH1(R132H) mutation provide mechanistic insights
      into transformation. In hematopoietic cells, inhibition of TET2 and histone
      demethylases leads to epigenetic alterations and accumulation of hematopoietic
      precursors. In the central nervous system, inhibition of collagen and prolyl
      hydroxylases lead to altered microenvironment and defective angiogenesis.

PMID- 22975372
TI  - Tailor-made renal cell carcinoma vaccines.
AB  - Cancer vaccines are beginning to show signs of clinical activity, but major
      uncertainties remain regarding antigen selection, strategy for immune
      stimulation, patient stratification, and monitoring of elicited response. A new
      study of peptide vaccines in advanced renal cell carcinoma patients provides
      important insights into these central issues.

PMID- 22975373
TI  - TGF-beta-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous
      metastases of HBV-positive hepatocellular carcinoma.
AB  - Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for
      patients with hepatocellular carcinoma (HCC). In this study, we uncovered a
      causative link between hepatitis B virus (HBV) infection and development of PVTT.
      Mechanistically, elevated TGF-beta activity, associated with the persistent
      presence of HBV in the liver tissue, suppresses the expression of microRNA-34a,
      leading to enhanced production of chemokine CCL22, which recruits regulatory T
      (Treg) cells to facilitate immune escape. These findings strongly suggest that
      HBV infection and activity of the TGF-beta-miR-34a-CCL22 axis serve as potent
      etiological factors to predispose HCC patients for the development of PVTT,
      possibly through the creation of an immune-subversive microenvironment to favor
      colonization of disseminated HCC cells in the portal venous system.

PMID- 22975374
TI  - EGF receptor is required for KRAS-induced pancreatic tumorigenesis.
AB  - Initiation of pancreatic ductal adenocarcinoma (PDA) is definitively linked to
      activating mutations in the KRAS oncogene. However, PDA mouse models show that
      mutant Kras expression early in development gives rise to a normal pancreas, with
      tumors forming only after a long latency or pancreatitis induction. Here, we show
      that oncogenic KRAS upregulates endogenous EGFR expression and activation, the
      latter being dependent on the EGFR ligand sheddase, ADAM17. Genetic ablation or
      pharmacological inhibition of EGFR or ADAM17 effectively eliminates KRAS-driven
      tumorigenesis in vivo. Without EGFR activity, active RAS levels are not
      sufficient to induce robust MEK/ERK activity, a requirement for epithelial
      transformation.

PMID- 22975375
TI  - EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal
      adenocarcinoma.
AB  - Clinical evidence indicates that mutation/activation of EGF receptors (EGFRs) is
      mutually exclusive with the presence of K-RAS oncogenes in lung and colon tumors.
      We have validated these observations using genetically engineered mouse models.
      However, development of pancreatic ductal adenocarcinomas driven by K-Ras
      oncogenes are totally dependent on EGFR signaling. Similar results were obtained
      using human pancreatic tumor cell lines. EGFRs were also essential even in the
      context of pancreatic injury and absence of p16Ink4a/p19Arf. Only loss of p53
      made pancreatic tumors independent of EGFR signaling. Additional inhibition of
      PI3K and STAT3 effectively prevented proliferation of explants derived from these
      p53-defective pancreatic tumors. These findings may provide the bases for more
      rational approaches to treat pancreatic tumors in the clinic.

PMID- 22975376
TI  - Control of tumor bioenergetics and survival stress signaling by mitochondrial
      HSP90s.
AB  - Tumors successfully adapt to constantly changing intra- and extracellular
      environments, but the wirings of this process are still largely elusive. Here, we
      show that heat-shock-protein-90-directed protein folding in mitochondria, but not
      cytosol, maintains energy production in tumor cells. Interference with this
      process activates a signaling network that involves phosphorylation of nutrient
      sensing AMP-activated kinase, inhibition of rapamycin-sensitive mTOR complex 1,
      induction of autophagy, and expression of an endoplasmic reticulum unfolded
      protein response. This signaling network confers a survival and proliferative
      advantage to genetically disparate tumors, and correlates with worse outcome in
      lung cancer patients. Therefore, mitochondrial heat shock protein 90s are
      adaptive regulators of tumor bioenergetics and tractable targets for cancer
      therapy.

PMID- 22975377
TI  - A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in
      multiple myeloma cells and overcomes bortezomib resistance.
AB  - Bortezomib therapy has proven successful for the treatment of
      relapsed/refractory, relapsed, and newly diagnosed multiple myeloma (MM);
      however, dose-limiting toxicities and the development of resistance limit its
      long-term utility. Here, we show that P5091 is an inhibitor of deubiquitylating
      enzyme USP7, which induces apoptosis in MM cells resistant to conventional and
      bortezomib therapies. Biochemical and genetic studies show that blockade of HDM2
      and p21 abrogates P5091-induced cytotoxicity. In animal tumor model studies,
      P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining
      P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers
      synergistic anti-MM activity. Our preclinical study therefore supports clinical
      evaluation of USP7 inhibitor, alone or in combination, as a potential MM therapy.

PMID- 22975378
TI  - Integrative analysis reveals an outcome-associated and targetable pattern of p53
      and cell cycle deregulation in diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is a clinically and biologically
      heterogeneous disease with a high proliferation rate. By integrating copy number
      data with transcriptional profiles and performing pathway analysis in primary
      DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that
      decreased p53 activity and perturbed cell cycle regulation. Primary tumors either
      had multiple complementary alterations of p53 and cell cycle components or
      largely lacked these lesions. DLBCLs with p53 and cell cycle pathway CNAs had
      decreased abundance of p53 target transcripts and increased expression of E2F
      target genes and the Ki67 proliferation marker. CNAs of the CDKN2A-TP53-RB-E2F
      axis provide a structural basis for increased proliferation in DLBCL, predict
      outcome with current therapy, and suggest targeted treatment approaches.

PMID- 22975379
TI  - Suppression of acquired docetaxel resistance in prostate cancer through depletion
      of notch- and hedgehog-dependent tumor-initiating cells.
AB  - Acquired resistance to Docetaxel precedes fatality in hormone-refractory prostate
      cancer (HRPC). However, strategies that target Docetaxel resistant cells remain
      elusive. Using in vitro and in vivo models, we identified a subpopulation of
      cells that survive Docetaxel exposure. This subpopulation lacks differentiation
      markers and HLA class I (HLAI) antigens, while overexpressing the Notch and
      Hedgehog signaling pathways. These cells were found in prostate cancer tissues
      and were related to tumor aggressiveness and poor patient prognosis. Notably,
      targeting Notch and Hedgehog signaling depleted this population through
      inhibition of the survival molecules AKT and Bcl-2, suggesting a therapeutic
      strategy for abrogating Docetaxel resistance in HRPC. Finally, these cells
      exhibited potent tumor-initiating capacity, establishing a link between
      chemotherapy resistance and tumor progression.

PMID- 22975380
TI  - Tumor type-dependent function of the par3 polarity protein in skin tumorigenesis.
AB  - Cell polarization is crucial during development and tissue homeostasis and is
      regulated by conserved proteins of the Scribble, Crumbs, and Par complexes. In
      mouse skin tumorigenesis, Par3 deficiency results in reduced papilloma formation
      and growth. Par3 mediates its tumor-promoting activity through regulation of
      growth and survival, since Par3 deletion increases apoptosis and reduces growth
      in vivo and in vitro. In contrast, Par3-deficient mice are predisposed to
      formation of keratoacanthomas, cutaneous tumors thought to originate from
      different cellular origin and frequently observed in humans. Par3 expression is
      reduced in both mouse and human keratoacanthomas, indicating tumor-suppressive
      properties of Par3. Our results identify a dual function of Par3 in skin cancer,
      with both pro-oncogenic and tumor-suppressive activity depending on the tumor
      type.

PMID- 22975382
TI  - Subtidal benthic macroinfaunal assemblages in tropical estuaries: generality
      amongst highly variable gradients.
AB  - South American estuaries are frequently not included in the search for general
      ecological models and studies dealing with biological assemblages in estuaries
      frequently do not sample the entire salinity gradient. We sampled three tropical
      estuaries, two times each, on ten stations distributed along each system. Six
      replicates were collected in each station for the benthic macroinfauna and
      sediment samples for grain size and inorganic contaminant analyses. There were
      finer sediments at the lower than at the upper estuarine portions. There was a
      decrease in the diversity, at family level, from marine to freshwater and the
      differences on the structure of the benthic assemblages were mostly spatial. In
      spite of the many different characteristics of the three estuaries (e.g.
      catchment size, pollution levels, proximity with the inner continental shelf)
      several consistent patterns of benthic macrofauna distribution along these
      systems were still observed. It suggested a general empirical model regarding the
      distribution of different benthic invertebrates along tropical salinity gradients
      which can be tested in different estuaries around the world.

PMID- 22975381
TI  - A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53
      degradation.
AB  - Twist proteins have been shown to contribute to cancer development and
      progression by impinging on different regulatory pathways, but their mechanism of
      action is poorly defined. By investigating the role of Twist in sarcomas, we
      found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2
      overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that
      Twist1 binds p53 C terminus through the Twist box. This interaction hinders key
      posttranslational modifications of p53 and facilitates its MDM2-mediated
      degradation. Our study suggests the existence of a Twist box code of p53
      inactivation and provides the proof of principle that targeting the Twist box:p53
      interaction might offer additional avenues for cancer treatment.

PMID- 22975383
TI  - Effects of regional climate changes on the planktonic ecosystem and water
      environment in the frozen Notoro Lagoon, northern Japan.
AB  - Diatom fossils from core sediments and living diatoms from water samples of
      Notoro Lagoon in northern Japan were examined to evaluate natural climate effects
      on lagoon environmental changes. In 1974, the artificial inlet was excavated.
      Immediately after, the anoxic bottom water in Notoro Lagoon began to disappear
      due to an increasing water exchange rate. However, chemical oxygen demand (COD)
      in the bottom water of Notoro Lagoon gradually increased, with fluctuations,
      during the last 30 years. In addition, the dominant diatom assemblages in Notoro
      Lagoon shifted to ice-related and spring bloom taxa after the excavation. The
      dominant taxa of each year in the sediment core were also strongly related to the
      timing of lagoon ice melting. This is because the COD in Notoro Lagoon was
      affected by the deposited volume of blooming diatoms, which was controlled by the
      duration of ice cover and the timing of ice discharge to the Okhotsk Sea likely
      due to an air pressure pattern change over the northern North Pacific like the
      Pacific Decadal Oscillation (PDO).

PMID- 22975384
TI  - Factors associated with positive findings from capsule endoscopy in patients with
      obscure gastrointestinal bleeding.
AB  - BACKGROUND & AIMS: Capsule endoscopy (CE) is used most frequently to identify
      causes of obscure gastrointestinal bleeding (OGIB). Identifying factors
      associated with the detection of lesions by CE could improve resource utilization
      and thereby improve patient selection for CE examination. We sought to identify
      clinical factors associated with positive findings from CE in patients with OGIB.
      METHODS: We analyzed data from 698 CE procedures performed between December 2001
      and April 2011 at St Paul's Hospital, Vancouver, Canada (50.3% of patients were
      female; mean age, 63.4 years). A positive finding was defined as a lesion that
      was believed to be the source of the bleeding (ulceration, mass lesion, vascular
      lesion, or visible blood). Univariate and multivariate logistic regression
      analyses were used to correlate demographic and clinical parameters with positive
      findings. RESULTS: A lesion believed to be the cause of bleeding was identified
      in 42% of cases. In univariate analysis, the number of
      esophagogastroduodenoscopies (EGDs), the presence of connective tissue disease or
      diabetes with end-organ damage, Charlson comorbidity index scores, and increasing
      transfusion requirements were significantly associated with identification of
      causative pathology from CE (all P < .027). In multivariate analysis, increasing
      number of EGDs (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.00-1.37),
      increasing transfusion requirements (3-9 units: OR, 1.70; 95% CI, 1.08-2.66, and
      >=10 units: OR, 2.72; 95% CI, 1.69-4.37), and connective tissue disease (OR,
      2.24; 95% CI, 1.14-4.41) were all significantly associated with identification of
      positive findings by using CE (all P < .045). CONCLUSIONS: Patients with a higher
      number of precapsule EGDs or transfusions, or connective tissue disease, are
      superior candidates for analysis of OGIB by CE.

PMID- 22975385
TI  - Discontinuation of low-dose aspirin therapy after peptic ulcer bleeding increases
      risk of death and acute cardiovascular events.
AB  - BACKGROUND & AIMS: Little is known about how discontinuation of low-dose aspirin
      therapy after peptic ulcer bleeding affects patient mortality or acute
      cardiovascular events. METHODS: We performed a retrospective cohort study by
      using data from patients who received low-dose aspirin therapy and were treated
      for bleeding peptic ulcers between 2007 and 2010 at Karolinska University
      Hospital, Stockholm, Sweden. We used a multivariable Cox regression model to
      adjust for potential confounders and analyze associations between discontinuation
      of low-dose aspirin therapy at discharge, death, and acute cardiovascular events.
      RESULTS: Of the 118 patients who received low-dose aspirin therapy, the therapy
      was discontinued for 47 (40%). During a median follow-up period of 2 years after
      hospital discharge, 44 of the 118 patients (37%) either died or developed acute
      cardiovascular events. Adjusting for confounders, patients with cardiovascular
      comorbidities who discontinued low-dose aspirin therapy had an almost 7-fold
      increase in risk for death or acute cardiovascular events (hazard ratio, 6.9; 95%
      confidence interval, 1.4-34.8) compared with patients who continued this therapy
      during the first 6 months of the follow-up period. A corresponding association
      was not observed among patients without cardiovascular comorbidities when the
      study began. CONCLUSIONS: In patients with cardiovascular disease,
      discontinuation of low-dose aspirin therapy after peptic ulcer bleeding increases
      risk of death and acute cardiovascular events almost 7-fold.

PMID- 22975386
TI  - The repAC replication system of the Rhizobium leguminosarum pRL7 plasmid is
      functional: implications regarding the origin and evolution of repABC plasmids.
AB  - The repABC replication/partitioning systems are commonly found in alpha
      proteobacteria plasmids and in secondary chromosomes. All of the elements
      required for their replication and stable maintenance are encoded within a single
      transcription unit: the repABC operon. The repC gene encodes an initiator
      protein, while RepA, RepB and centromere-like sequence (parS) direct plasmid
      segregation. Strains containing two or more repABC plasmids are a common feature
      in some alpha proteobacteria groups, indicating that the repABC plasmid family
      embraces several incompatibility groups. Genes encoded within repABC operons are
      highly dynamic: each one possess its own distinctive phylogeny and homologous
      recombination events are common within these operons. Additionally, alpha
      proteobacterial genomes contain repAB genes not associated with the ctRNA or with
      repC as well as plasmids whose replication depends on a ctRNA-repC module without
      the participation of repAB genes. Some alphaproteobacteria have repC genes
      clustered with other genes that are not involved in replication/partitioning
      functions. These atypical associations of genes could have an important role in
      the origin and diversification of new plasmids. Here we evaluated the
      functionality and possible evolutionary consequences of one of these atypical
      gene associations: the repAC genes present in the Rhizobium leguminosarum plasmid
      pRL7. The repAC genes are organized in an operon and they are capable of
      sustaining replication but in an unstable manner. RepC was essential for
      replication, and the origin of replication resides within its coding region. In
      contrast, RepA plays a minor role in the negative regulation of its own
      transcription.

PMID- 22975387
TI  - Ethical issues and challenges in pressure ulcer research - the research nurses'
      perspective.
AB  - AIM OF STUDY: This paper explores the issues faced by research nurses in pressure
      ulcer research through reflection on our own practice and subsequently addresses
      these issues through critical appraisal of the existing literature. METHODS: A
      critical reflection framework which provided an opportunity for group reflection
      and reflexivity was adopted to guide our reflection. Focus questions were
      formulated based on our reflections and used to inform our literature review.
      Keywords used in the literature review search included 'research nurse', ethical
      principles, ethical issues and reflection. A formal tool was used to appraise
      normative ethics articles. RESULTS: Reflection on our practice in pressure ulcer
      research identified four main issues: informed consent, confidentiality,
      methodological uncertainties and more generally the ethical dilemma of the
      conflict between our accountability and responsibility to the patients and
      obligations to the research studies. The notion of 'power relations' was found to
      permeate our practice as research nurses at all level. Six normative ethics
      papers were retrieved and critically appraised to aid our personal and
      professional learning and development in the conduct of ethical practice as
      research nurses in pressure ulcer research through the theory of practice which
      other research nurses and/or nurse researchers used in other disciplines.
      CONCLUSIONS: Four main ethical challenges and the issue of power relation were
      highlighted. Our reflection and the appraisal of the literature provided us the
      necessary knowledge and skills to better navigate these ethical challenges in the
      future.

PMID- 22975388
TI  - Melanoma cell adhesion molecule identifies encephalitogenic T lymphocytes and
      promotes their recruitment to the central nervous system.
AB  - In multiple sclerosis, encephalitogenic CD4(+) lymphocytes require adhesion
      molecules to accumulate into central nervous system inflammatory lesions. Using
      proteomic techniques, we identified expression of melanoma cell adhesion molecule
      (MCAM) on a subset of human effector memory CD4(+) lymphocytes and on human blood
      brain barrier endothelium. Herein, we demonstrate that MCAM is a stable surface
      marker that refines the identification of interleukin 17(+), interleukin 22(+),
      RAR-related orphan receptor gamma and interleukin 23 receptor(+) cells within the
      CD161(+)CCR6(+) subset of memory CD4(+) lymphocytes. We also show that MCAM(+)
      lymphocytes express significantly more granulocyte/macrophage colony stimulating
      factor and granzyme B than MCAM(-) lymphocytes. Furthermore, the proportion of
      MCAM(+) CD4(+) lymphocytes is significantly increased in the blood and in the
      central nervous system of patients with multiple sclerosis and experimental
      autoimmune encephalomyelitis animals compared with healthy controls or other
      neurological diseases, and MCAM expression is upregulated at the blood-brain
      barrier within inflammatory lesions. Moreover, blockade of MCAM or depletion of
      MCAM(+) CD4(+) T lymphocytes both restrict the migration of T(H)17 lymphocytes
      across blood-brain barrier endothelial cells and decrease the severity of
      experimental autoimmune encephalomyelitis. Our findings indicate that MCAM could
      serve as a potential biomarker for multiple sclerosis and represents a valuable
      target for the treatment of neuroinflammatory conditions.

PMID- 22975389
TI  - Single-subject oscillatory gamma responses in tinnitus.
AB  - This study used magnetoencephalography to record oscillatory activity in a group
      of 17 patients with chronic tinnitus. Two methods, residual inhibition and
      residual excitation, were used to bring about transient changes in spontaneous
      tinnitus intensity in order to measure dynamic tinnitus correlates in individual
      patients. In residual inhibition, a positive correlation was seen between
      tinnitus intensity and both delta/theta (6/14 patients) and gamma band (8/14
      patients) oscillations in auditory cortex, suggesting an increased
      thalamocortical input and cortical gamma response, respectively, associated with
      higher tinnitus states. Conversely, 4/4 patients exhibiting residual excitation
      demonstrated an inverse correlation between perceived tinnitus intensity and
      auditory cortex gamma oscillations (with no delta/theta changes) that cannot be
      explained by existing models. Significant oscillatory power changes were also
      identified in a variety of cortical regions, most commonly midline lobar regions
      in the default mode network, cerebellum, insula and anterior temporal lobe. These
      were highly variable across patients in terms of areas and frequency bands
      involved, and in direction of power change. We suggest a model based on a local
      circuit function of cortical gamma-band oscillations as a process of mutual
      inhibition that might suppress abnormal cortical activity in tinnitus. The work
      implicates auditory cortex gamma-band oscillations as a fundamental intrinsic
      mechanism for attenuating phantom auditory perception.

PMID- 22975391
TI  - Single nucleotide polymorphisms associated with sporadic brain arteriovenous
      malformations: where do we stand?
AB  - Brain arteriovenous malformations are characterized by a tangle of abnormal
      vessels directly shunting blood from the arterial to venous circulation. They are
      known to occur either sporadically or in the context of well-defined genetic
      disorders. Haemorrhage represents the most severe clinical manifestation, whereas
      other common symptoms include headache, seizures and neurological deficits.
      Although sporadic forms do not recognize a specific genetic cause, in recent
      years, it has been hypothesized that genes involved in angiogenesis and
      inflammation or coding for proteins, such as fibronectins, laminins and
      integrins, may play a role in the pathophysiology of brain arteriovenous
      malformations. More recently, a new trend of genetic studies has investigated the
      association between sporadic arteriovenous malformations and single nucleotide
      polymorphisms, single base variations between genomes within members of a
      biological species or between paired chromosomes in an individual, which may
      determine the susceptibility to develop complex diseases and influence their
      natural history. Several polymorphisms in two different families of genes have
      been associated with disease susceptibly and increased haemorrhagic risk. These
      genes are mainly involved in the inflammatory cascade and in the regulation of
      angiogenesis. However, most of the investigated polymorphisms have been selected
      on the basis of candidate genes because of their potential functional role in the
      pathogenesis of brain arteriovenous malformations or in other cerebrovascular
      diseases. Only one hypothesis-free genome-wide association study in a small
      number of patients has been performed so far, but it was unable to identify
      significant associations between brain arteriovenous malformations and specific
      genetic loci. In this article, we review and analyse the polymorphisms
      investigated to date in association with sporadic brain arteriovenous
      malformations in the medical literature. We discuss the biological,
      pathophysiological and clinical implications of these studies, with particular
      attention to the prediction of haemorrhagic risk and the possibility of building
      genetic profiles capable of defining the architectural features of the
      malformations and predict their evolution and natural history. We also present a
      joint analysis of the risk estimates found by the studies in literature that have
      evaluated the association between single nucleotide polymorphisms and brain
      arteriovenous malformation susceptibility and risk of bleeding. This analysis
      shows a statistically significant association between the interleukin 6 -174G>C
      (odds ratio = 1.97; 95% confidence interval: 1.15-3.38) and the tumour necrosis
      factor alpha -238G>A (odds ratio = 2.19; 95% confidence interval: 1.25-3.83) gene
      polymorphisms and risk of intracranial haemorrhage and between the activin-like
      kinase 1 (also known as ACVRL1) intervening sequence 3 -35A>G (odds ratio = 2.42;
      95% confidence interval: 1.54-3.8) gene polymorphism and disease susceptibility.

PMID- 22975390
TI  - Atypical face shape and genomic structural variants in epilepsy.
AB  - Many pathogenic structural variants of the human genome are known to cause facial
      dysmorphism. During the past decade, pathogenic structural variants have also
      been found to be an important class of genetic risk factor for epilepsy. In other
      fields, face shape has been assessed objectively using 3D stereophotogrammetry
      and dense surface models. We hypothesized that computer-based analysis of 3D face
      images would detect subtle facial abnormality in people with epilepsy who carry
      pathogenic structural variants as determined by chromosome microarray. In 118
      children and adults attending three European epilepsy clinics, we used an
      objective measure called Face Shape Difference to show that those with pathogenic
      structural variants have a significantly more atypical face shape than those
      without such variants. This is true when analysing the whole face, or the
      periorbital region or the perinasal region alone. We then tested the predictive
      accuracy of our measure in a second group of 63 patients. Using a minimum
      threshold to detect face shape abnormalities with pathogenic structural variants,
      we found high sensitivity (4/5, 80% for whole face; 3/5, 60% for periorbital and
      perinasal regions) and specificity (45/58, 78% for whole face and perinasal
      regions; 40/58, 69% for periorbital region). We show that the results do not seem
      to be affected by facial injury, facial expression, intellectual disability, drug
      history or demographic differences. Finally, we use bioinformatics tools to
      explore relationships between facial shape and gene expression within the
      developing forebrain. Stereophotogrammetry and dense surface models are powerful,
      objective, non-contact methods of detecting relevant face shape abnormalities. We
      demonstrate that they are useful in identifying atypical face shape in adults or
      children with structural variants, and they may give insights into the molecular
      genetics of facial development.

PMID- 22975392
TI  - Purkinje cell fusion and binucleate heterokaryon formation in multiple sclerosis
      cerebellum.
AB  - A major conceptual consideration in both endogenous and therapeutic central
      nervous system repair is how damaged (or senescent) neurons, given their often
      enormously complex and extensive network of connections, can possibly be
      replaced. The recent observation of fusion of circulating bone marrow cells with,
      in particular, cerebellar Purkinje cells, as well as the subsequent formation of
      stable heterokaryons, offers a tantalizing potential solution to this difficulty.
      Here, we have explored Purkinje cell fusion and heterokaryon formation in the
      human brain and the influence of central nervous system inflammation. We analysed
      post-mortem cerebellum tissue from patients who had multiple sclerosis and from
      appropriate controls. Purkinje cells were analysed for heterokaryon formation
      using immunohistochemistry techniques and chromosome composition using
      fluorescence in situ hybridization. For the first time in humans we show a
      disease-related increase in Purkinje cell fusion and heterokaryon formation. We
      have shown that heterokaryon formation takes place in control subjects, and that
      the frequency of this event is considerably increased in patients with multiple
      sclerosis, the prototypical inflammatory brain disease, with ~0.4% of Purkinje
      cells being binucleate heterokaryons. No mononucleate polyploid Purkinje cell
      heterokaryons were found. The observation that heterokaryon formation in the
      cerebellum occurs as part of the central nervous system inflammatory reaction
      suggests a potential mechanism of neural repair. It also suggests an exciting new
      avenue for therapeutic intervention, as enhancement or manipulation of fusion
      events may have a therapeutic role in cellular protection in multiple sclerosis.

PMID- 22975393
TI  - The relationship between antenatal care and preterm birth: the importance of
      content of care.
AB  - BACKGROUND: Antenatal care can play an important role in the prevention of
      preterm birth. Evaluation of antenatal care is usually based on the number of
      visits rather than the content of care, using tools such as the Adequacy of
      Prenatal Care Use index. This article presents an analysis of the relation
      between specific elements of antenatal care and the risk of preterm birth
      compared with considering the number of visits only. METHODS: A prospective
      cohort study was conducted in the Brussels Metropolitan Region. In all, 333 women
      were consecutively recruited at the beginning of their antenatal care trajectory
      and followed until birth. Information on timing and content for every visit was
      recorded by structured interview. A new tool was developed to measure the
      antenatal care trajectory, which included Content and Timing of care in Pregnancy
      (CTP). Odds ratios (OR) (adjusted and unadjusted) for preterm birth were
      calculated for the Adequacy of Prenatal Care Use and CTP model. RESULTS: The
      number of visits alone was not associated with preterm birth. In contrast, a
      significant association was found between the content and timing of care and
      preterm birth. Compared with the CTP lowest ('inadequate') category, women in the
      CTP 'sufficient' (OR 0.30; 95% CI 0.09-0.94) and CTP 'appropriate' (OR 0.21; 95%
      CI 0.06-0.68) category had a lower risk. CONCLUSIONS: This study suggests that
      measurement of the content and timing of care of antenatal care using the new CTP
      tool is a better assessment of the risk of preterm birth than assessment of the
      number of antenatal visits alone.

PMID- 22975394
TI  - High capacity magnetic mesoporous carbon-cobalt composite adsorbents for removal
      of methylene green from aqueous solutions.
AB  - Mesoporous carbons containing cobalt nanoparticles are synthesized by tri-or quad
      constituent self assembly of Pluronic F127, phenol-formaldehyde oligomer (resol),
      cobalt acetylacetonate (acac), and optionally tetraethyl orthosilicate (TEOS,
      optional). Upon pyrolysis in N(2) atmosphere, the resol provides sufficient
      carbon yield to maintain the ordered structure, while decomposition of the
      Co(acac) yields cobalt nanoparticles. To provide increased surface area, the
      dispersed silicate from condensation of TEOS can be etched after carbonization to
      yield micropores, Without silica templated micropores, the surface area decreases
      as the cobalt content increases, but there is a concurrent increase in the volume
      average pore diameter (BHJ) and a dramatic increase in the adsorption capacity of
      methylene green with the equilibrium adsorption capacity from 2 to 90 mg/g with
      increasing Co content. Moreover, the surface area and pore size of mesoporous
      composites can be dramatically increased by addition of TEOS and subsequent
      etching. These composites exhibit extremely high adsorption capacity up to 1151
      mg/g, which also increases with increases in the Co content. Additionally, the
      inclusion of cobalt nanoparticles provides magnetic separation from aqueous
      suspension. The in situ synthesis of the Co nanoparticles yields to a carbon
      shell that can partially protect the Co from leaching in acidic media; after 96 h
      in 2 M HCl, the powders remain magnetic.

PMID- 22975395
TI  - Facile synthesis of nanocrystal encoded fluorescent silica microspheres.
AB  - Monodisperse CdTe composite microspheres with a spherical shape were prepared
      using organosilane chemicals in aqueous solution. CdTe nanocrystals (NCs) were
      loaded into the matrix of silica microspheres during the formation of composite
      microspheres. Detailed characterization of the CdTe composite microspheres by
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      spectrofluorimeter was performed to elucidate the morphology and fluorescence of
      the composite microspheres. In contrast to CdTe NCs in aqueous solution, CdTe NCs
      in the composite microspheres revealed high stability and fluorescence due to the
      confined effects of silica matrix. In addition, multicolored CdTe QDs were
      encoded into the microspheres at precise ratios.

PMID- 22975396
TI  - The interaction of insulin, glucose, and insulin-glucose mixtures with a
      phospholipid monolayer.
AB  - We determined how glucose or insulin interacts with a phospholipid monolayer at
      the air/water interface and explained these mechanisms from a physico-chemical
      point of view. The 1,2-dipalmitoyl-2-sn-glycero-3-phosphatidylcholine (DPPC)
      monolayer at an air/water interface acted as a model membrane, which allowed the
      effect of the molecular packing density in the monolayer on the interactions to
      be determined. The interaction of glucose, insulin, and a mixture of glucose and
      insulin to the DPPC monolayer were investigated via surface pressure-area per
      molecule Langmuir isotherms and fluorescence microscopy. Glucose adsorbed to the
      underside of the DPPC monolayer, while insulin was able to penetrate through the
      monolayer when the phospholipid molecules were not densely packed. The presence
      of a mixture of insulin and glucose affected the molecular packing in the DPPC
      monolayer differently than the pure insulin or glucose solutions, and the glucose
      insulin mixture was seen to be able to penetrate through the monolayer. These
      results indicated that glucose and insulin interact with one another, giving a
      material that may then transported through a pore in the monolayer or through the
      spaces between the molecules of the monolayer.

PMID- 22975397
TI  - Complexation of bovine serum albumin and sugar beet pectin: stabilising oil-in
      water emulsions.
AB  - In a previous study (Langmuir 28 (2012) 10164-10176.), we investigated the
      complexation of bovine serum albumin (BSA) with sugar beet pectin (SBP). A pH
      composition phase diagram was established and structural transitions in relation
      to the phase diagram during complexation were identified. The present study
      examines the implications of these interactions on the emulsifying performance of
      BSA/SBP mixtures. Middle-chain triglycerides (MCTs) in water emulsions were
      prepared using conditions corresponding to different regions of the phase
      diagram. At high pHs and in the stable region of mixed individual soluble
      polymers where complexation is absent, there is no improved emulsifying
      performance, compared with the individual protein and polysaccharide. For these
      mixtures, the emulsion characteristics are controlled by the major component in
      the solutions, as determined by the competitive adsorption of the two components
      at the oil-water interface. At low pHs and low BSA/SBP ratios, and so mainly
      within the stable region of intramolecular soluble complexes, BSA/SBP mixtures
      greatly improve the stability of emulsions. Here, stabilisation is controlled by
      the cooperative adsorption of the two components at the oil-water interface.
      Through electrostatic complexation BSA promotes the adsorption of SBP on to
      interfaces to form a thick steric layer around emulsion droplets and thus
      providing better stability. At low pHs and high BSA/SBP ratios, that is, mainly
      within the unstable region of intermolecular insoluble complexes, emulsions
      prepared are extremely unstable due to bridging flocculation between emulsion
      droplets.

PMID- 22975398
TI  - Synthesis of mesoporous magnetic Co-NPs/carbon nanocomposites and their
      adsorption property for methyl orange from aqueous solution.
AB  - Mesoporous magnetic Co-NPs(nanoparticles)/carbon nanocomposites were synthesized
      by carbonization of polyacrylonitrile (PAN) microspheres entrapped with cobalt
      salt for the first time. The structure and morphology of the porous magnetic
      nanocomposites were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), vibrating sample magnetometry (VSM), and N(2)
      adsorption-desorption technique. The nanocomposites possess very high saturation
      magnetization (Ms is up to ~133 emu/g), near-zero remanence, and very low
      coercivity (Hc is down to ~0.023 KOe). Meanwhile, the nanocomposites have
      mesoporous structure with average pore size of 4 nm and high specific surface
      area of 232 m(2)/g, which can be tuned by changing the carbonization conditions.
      Using methyl orange (MO) as model pollutant in water, the mesoporous magnetic
      nanocomposites showed good adsorption capacity of 380 mg/g, and the absorbed MO
      could be easily released in ethanol. The mesoporous nanocomposites were facile
      separated from solution under external magnetic force, and over 85% adsorption
      capacity for MO could be retained after five adsorption/desorption cycles.

PMID- 22975399
TI  - Embossing of organic thin films using a surfactant assisted lift-off technique.
AB  - A simple technique for patterning organic materials using a surfactant assisted
      lift-off method is proposed. Thin films of various organic materials are
      prepared, and areas in contact with a surfactant coated poly(dimethylsiloxane)
      (PDMS) stamp are selectively removed. The general applicability of this technique
      is shown for materials containing nitrate, amine, and carboxylic acid functional
      groups. This technique provides a new methodology for fabricating patterns with
      vertical dimensions ranging from 30 nm up to 3 MUm on organic thin films with
      specific functional groups.

PMID- 22975400
TI  - Large-surface mesoporous TiO2 nanoparticles: synthesis, growth and photocatalytic
      performance.
AB  - This study demonstrates a facile and effective method to generate mono-dispersed
      titanium dioxide spheres at ambient conditions. The size of the colloids can be
      controlled from 60 to 500 nm by optimizing experimental parameters (e.g.,
      concentration, time, and temperature). Anatase TiO(2) can be obtained through
      titanium glycolate colloids generated in acetone via two ways: water boiling
      approach and calcination at a high temperature of 500 degrees C. Particle
      characteristics (shape, size, and size distribution) were measured by advanced
      techniques, including transmission electron microscope (TEM), thermo-gravimetric
      analysis (TGA), UV/Vis absorption spectrum, nitrogen gas adsorption and
      desorption isotherms Brunauer-Emmett-Teller (BET) surface area measurement, and X
      ray diffraction technique (XRD). The possible mechanism of nucleation and growth
      of such colloids was discussed. The role of acetone in the formation and growth
      of titanium glycolate colloids was also investigated by Fourier transform
      infrared (FT-IR) spectroscopy. Finally, the photocatalysis performance of such
      anatase TiO(2) particles was tested and proved to be efficient in degradation of
      organic dyes (e.g., phenolphthalein and methly orange).

PMID- 22975401
TI  - Cardiac stem cell therapy to modulate inflammation upon myocardial infarction.
AB  - BACKGROUND: After myocardial infarction (MI) a local inflammatory reaction clears
      the damaged myocardium from dead cells and matrix debris at the onset of scar
      formation. The intensity and duration of this inflammatory reaction are
      intimately linked to post-infarct remodeling and cardiac dysfunction. Strikingly,
      treatment with standard anti-inflammatory drugs worsens clinical outcome,
      suggesting a dual role of inflammation in the cardiac response to injury. Cardiac
      stem cell therapy with different stem or progenitor cells, e.g. mesenchymal stem
      cells (MSC), was recently found to have beneficial effects, mostly related to
      paracrine actions. One of the suggested paracrine effects of cell therapy is
      modulation of the immune system. SCOPE OF REVIEW: MSC are reported to interact
      with several cells of the immune system and could therefore be an excellent means
      to reduce detrimental inflammatory reactions and promote the switch to the
      healing phase upon cardiac injury. This review focuses on the potential use of
      MSC therapy for post-MI inflammation. To understand the effects MSC might have on
      the post-MI heart the cellular and molecular changes in the myocardium after MI
      need to be understood. MAJOR CONCLUSIONS: By studying the general pathways
      involved in immunomodulation, and examining the interactions with cell types
      important for post-MI inflammation, it becomes clear that MSC treatment might
      provide a new therapeutic opportunity to improve cardiac outcome after acute
      injury. GENERAL SIGNIFICANCE: Using stem cells to target the post-MI inflammation
      is a novel therapy which could have considerable clinical implications. This
      article is part of a Special Issue entitled Biochemistry of Stem Cells.

PMID- 22975402
TI  - Transversus abdominis plane (TAP) blocks-a review.
AB  - INTRODUCTION: Effective post-operative pain management can positively influence
      patient outcome. Multimodal analgesic regimes are often limited by side-effects.
      Epidural analgesia may be resource-consuming, restrict mobility and have negative
      cardiovascular and gastrointestinal consequences. Consequently, there is a need
      for regional anaesthetic techniques to minimise opioid use, and provide
      alternatives to epidurals, especially within the context of minimally invasive
      abdominal surgery and enhanced recovery programmes. This review aims to evaluate
      the evidence base underlying Transversus abdominis plane (TAP) blockade. METHODS:
      A literature search was performed using the PubMed database
      (http://www.ncbi.nlm.nih.gov/pubmed/) using the parameters 'transversus abdominis
      plane' and 'TAP'. The references within were then searched for applicable
      studies. Case reports and correspondence were excluded. FINDINGS: Thirteen
      studies assessed technique and mechanisms of action. Fourteen clinical studies
      involved a total of 1250 patients. Seven studies (6 Randomised Controlled Trials,
      RCTs) demonstrated reductions in post-operative morphine requirements (33.3%
      73.1%). Five RCTs demonstrated concomitant improvements in pain scores. Five RCTs
      demonstrated reduced opioid side effects. The one study assessing functional
      outcome (a Prospective Controlled Trial, PCT) demonstrated earlier return of
      gastrointestinal function and hospital discharge. CONCLUSION: The limited
      evidence to date suggests that TAP blockade is an effective adjunct to multimodal
      post-operative analgesia following a range of abdominal surgical procedures.
      Whether TAP blocks are a viable alternative to epidural analgesia remains to be
      determined. However, it is likely that as this technique grows in popularity its
      role, particularly that in enhanced recovery programmes, will be better
      delineated and refined.

PMID- 22975403
TI  - [Hypotension from endocrine origin].
AB  - Hypotension is defined by a low blood pressure either permanently or only in
      upright posture (orthostatic hypotension). In contrast to hypertension, there is
      no threshold defining hypotension. The occurrence of symptoms for systolic and
      diastolic measurements respectively below 90 and 60 mm Hg establishes the
      diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or
      an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to
      adrenal failure from adrenal or central origin, isolated hypoaldosteronism,
      pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoid
      syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism
      associates low blood sodium and above all high blood potassium levels. They are
      generally classified according to their primary (hyperreninism) or secondary
      (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in
      adults (intensive care unit, selective injury of the glomerulosa area) and in
      children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism
      is related to mellitus diabetes complicated with dysautonomia, kidney failure,
      age, iatrogenic factors, and HIV infections. In both cases, they can be
      associated to glucocorticoid insufficiency from primary adrenal origin (adrenal
      failure of various origins with hyperreninism, among which congenital 21
      hydroxylase deficiency with salt loss) or from central origin (hypopituitarism
      with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1
      pseudohypoaldosteronism) or acquired states of resistance to aldosterone.
      Acquired salt losses from enteric (total colectomy with ileostomy) or renal
      (interstitial nephropathy, Bartter and Gitelman syndromes...) origin might be
      responsible for hypotension and are associated with hyperreninism
      hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas,
      especially during surgical removal when the patient has not been prepared with
      calcium inhibitors. Every flush with hypotension should suggest a carcinoid
      crisis, which is very sensitive to subcutaneous somatostatin analog. An accurate
      etiological diagnosis should allow treat efficiently endocrine hypotension
      without inducing hypertension in supine posture.

PMID- 22975404
TI  - Signaling pathways used by EGF to stimulate conjunctival goblet cell secretion.
AB  - The purpose of this study was to identify the signaling pathways that epidermal
      growth factor (EGF) uses to stimulate mucin secretion from cultured rat
      conjunctival goblet cells and to compare the pathways used by EGF with those used
      by the known secretagogue muscarinic, cholinergic agonists. To this end, goblet
      cells from rat conjunctiva were grown in culture using RPMI media. For
      immunofluorescence experiments, antibodies against EGF receptor (EGFR) and ERK 2
      as well as muscarinic receptors (M(1)AchR, M(2)AchR, and M(3)AchR) were used, and
      the cells viewed by fluorescence microscopy. Intracellular [Ca(2+)] ([Ca(2+)](i))
      was measured using fura 2/AM. Glycoconjugate secretion was determined after
      cultured goblet cells were preincubated with inhibitors, and then stimulated with
      EGF or the cholinergic agonist carbachol (Cch). Goblet cell secretion was
      measured using an enzyme-linked lectin assay with UEA-I or ELISA for MUC5AC. In
      cultured goblet cells EGF stimulated an increase in [Ca(2+)](i) in a
      concentration-dependent manner. EGF-stimulated increase in [Ca(2+)](i) was
      blocked by inhibitors of the EGF receptor and removal of extracellular Ca(2+).
      Inhibitors against the EGFR and ERK 1/2 blocked EGF-stimulated mucin secretion.
      In addition, cultured goblet cells expressed M(1)AchR, M(2)AchR, and M(3)AchRs.
      Cch-stimulated increase in [Ca(2+)](i) was blocked by inhibitors for the
      M(1)AchRs, matrix metalloproteinases, and EGF receptors. Inhibitors against the
      EGF receptor and ERK 1/2 also blocked Cch-stimulated mucin secretion. We conclude
      that in conjunctival goblet cells, EGF itself increases [Ca(2+)](i) and activates
      ERK 1/2 to stimulate mucin secretion. EGF-stimulated secretion is dependent on
      extracellular Ca(2+). This mechanism of action is similar to cholinergic agonists
      that use muscarinic receptors to transactivate the EGF receptor, increase
      [Ca(2+)](i), and activate ERK 1/2 leading to an increase in mucin secretion.

PMID- 22975406
TI  - Emerging opportunities for allosteric modulation of G-protein coupled receptors.
AB  - Their ubiquitous nature, wide cellular distribution and versatile molecular
      recognition and signalling help make G-protein binding receptors (GPCRs) the most
      important class of membrane proteins in clinical medicine, accounting for ~40% of
      all current therapeutics. A large percentage of current drugs target the
      endogenous ligand binding (orthosteric) site, which are structurally and
      evolutionarily conserved, particularly among members of the same GPCR subfamily.
      With the recent advances in GPCR X-ray crystallography, new opportunities for
      developing novel subtype selective drugs have emerged. Given the increasing
      recognition that the extracellular surface conformation changes in response to
      ligand binding, it is likely that all GPCRs possess an allosteric site(s) capable
      of regulating GPCR signalling. Allosteric sites are less structurally conserved
      than their corresponding orthosteric site and thus provide new opportunities for
      the development of more selective drugs. Constitutive oligomerisation
      (dimerisation) identified in many of the GPCRs investigated, adds another
      dimension to the structural and functional complexity of GPCRs. In this review,
      we compare 60 crystal structures of nine GPCR subtypes (rhodopsin, beta2-AR,
      beta1-AR, A(2a)-AR, CXCR4, D3R, H1R, M2R, M3R) across four subfamilies of Class A
      GPCRs, and discuss mechanisms involved in receptor activation and potential
      allosteric binding sites across the highly variable extracellular surface of
      these GPCRs. This analysis has identified a new extracellular salt bridge (ESB-2)
      that might be exploited in the design of allosteric modulators.

PMID- 22975405
TI  - Opportunities for functional selectivity in GPCR antibodies.
AB  - Monoclonal antibodies (mAbs) have been used for decades as tools to probe the
      biology and pharmacology of receptors in cells and tissues. They are also
      increasingly being developed for clinical purposes against a broad range of
      targets, albeit to a lesser extent for G-protein-coupled receptors (GPCRs)
      relative to other therapeutic targets. Recent pharmacological, structural and
      biophysical data have provided a great deal of new insight into the molecular
      details, complexity and regulation of GPCR function. Whereas GPCRs used to be
      viewed as having either "on" or "off" conformational states, it is now recognized
      that their structures may be finely tuned by ligands and other interacting
      proteins, leading to the selective activation of specific signaling pathways.
      This information coupled with new technologies for the selection of mAbs
      targeting GPCRs will be increasingly deployed for the development of highly
      selective mAbs that recognize conformational determinants leading to novel
      therapeutics.

PMID- 22975407
TI  - Instant hot noodles: do they need to burn?
AB  - BACKGROUND: Scalds and contact burns in children may occur as the result of
      spillage of hot food and drinks, including instant hot noodles. This study sought
      to determine the frequency of noodle burns in children and investigate the
      thermal properties of instant hot noodles. METHODS: Data on instant hot noodle
      burns in children were retrieved from the New South Wales Severe Burn Injury
      Database between 2005 and 2010. Five widely available brands of instant hot
      noodles, including three cup and two packet varieties, were prepared following
      the manufacturer's instructions. For each preparation the initial temperature
      after cooking was recorded, together with the time to cool to 50 degrees C.
      RESULTS: 291 children sustained instant hot noodle burns over the 6 year study
      period, representing 5.4% of all children referred to our burns unit. Over a
      third received inadequate first aid. Cup noodles cooked with boiling water
      reached the highest temperature of over 80 degrees C and took the longest time to
      cool to 50 degrees C: on average 52.3 min. Cup noodles in smaller, narrower
      containers achieved higher post-cooking temperatures compared to noodles in
      wider, bowel shaped containers. Packet noodles cooked in a Microwave oven
      attained lower peak temperatures and shorter cooling times compared to cup
      noodles. CONCLUSIONS: Although relatively uncommon in children, instant hot
      noodle burns often received inadequate first aid. When cooked according to
      manufacturer's instructions, noodles generally exceeded temperatures sufficient
      to cause a burn. Consumers and parents need to be aware of the risks of burn when
      preparing these foods.

PMID- 22975408
TI  - Ten-year experience in face and neck unit reconstruction using tissue expanders.
AB  - BACKGROUND: Tissue expansion allows optimal aesthetic reconstruction by the use
      of a similar adjacent tissue to reconstruct a defect without creation of
      significant donor site morbidity, especially in the face and upper neck area.
      METHODS: A total of 78 patients underwent facial reconstruction by insertion of a
      tissue expander (TE) in the cheek or the neck due to burn scar, traumatic scar,
      leschmaniasis or large pigmented nevi. RESULTS: All reconstructions were
      completed satisfactorily; complications were: complete extrusion (2.6%),
      incomplete extrusion (3.8%), partial necrosis (14.1%), haematoma (6.4%), wide
      scar (33.3%), hypertrophic scar (17.9%), lower lid ectropion (1.3%), post
      expansion atrophy (2.6%), permanent decrement in sensation (1.3%), sagging
      (14.1%) and infection (2.6%). CONCLUSIONS: The lateral facial areas and neck
      contain essentially the same type of skin; hence, tissue expansion allows optimal
      aesthetic reconstruction by the use of a similar adjacent tissue and expanding
      either the lower face or the neck interchangeably without creation of major donor
      site morbidity; even when we use free flaps for coverage, although we achieved
      good contour and sufficient bulk, but due to poor colour match, reconstruction
      with expanded skin of the upper neck is needed for better result.

PMID- 22975409
TI  - Neuroprotection afforded by antagonists of endothelin-1 receptors in experimental
      stroke.
AB  - Endothelin-1 (ET-1) is involved on the development of cerebral edema in acute
      ischemic stroke. As edema is a therapeutic target in cerebral ischemia, our aim
      was to study the effect of antagonists for ET-1 receptors (Clazosentan(r) and BQ
      788, specific antagonists for receptors A and B, respectively) on the development
      of edema, infarct volume and sensorial-motor deficits in rats subjected to
      ischemia by occlusion of the middle cerebral artery (MCAO). We used Wistar rats
      (280-320 g) submitted to ischemia by intraluminal transient (90 min) MCAO. After
      ischemia, rats were randomized into 4 groups (n = 6) treated with; 1) control
      group (saline), 2) Clazosentan(r) group (10 mg/kg iv), 3) BQ-788 group (3 mg/kg
      iv), and 4) combined treatment (Clazosentan(r) 10 mg/kg plus BQ-788 3 mg/kg iv).
      We observed that rats treated with Clazosentan(r) showed a reduction of edema,
      measured by MRI, at 72 h (hours) and at day 7 (both p < 0.0001), and a decrease
      in the serum levels of ET-1 at 72 h (p < 0.0001) and at day 7 (p = 0.009). The
      combined treatment also induced a reduction of edema at 24 h (p = 0.004), 72 h (p
      < 0.0001) and at day 7 (p < 0.0001), a reduction on infarct volume, measured by
      MRI, at 24 and 72 h, and at day 7 (all p < 0.01), and a better sensorimotor
      recovery at 24 and 72 h, and at day 7 (all p < 0.01). Moreover, Clazosentan(r)
      induced a decrease in AQP4 expression, while BQ-788 induced an increase in AQP9
      expression. These results suggest that antagonists for ET-1 receptors may be a
      good therapeutic target for cerebral ischemia.

PMID- 22975411
TI  - Awareness of periconceptional folic acid supplementation among Nepalese women of
      childbearing age: a cross-sectional study.
AB  - OBJECTIVE: Maternal folate deficiency is associated with neural tube defects
      (NTDs), the most common congenital birth defect at Maternity Hospital, Kathmandu,
      Nepal. NTDs can be prevented with periconceptional folic acid supplementation
      (FAS). This study was performed to assess the awareness of FAS among women of
      reproductive age in Kathmandu. METHODS: A semi-structured questionnaire was
      administered to 400 randomly selected patients aged 15 to 45 years visiting
      Kathmandu Model Hospital from May to July 2011, seeking any awareness of FAS,
      knowledge of its impact on fetal development and knowledge of the appropriate
      time of supplementation. RESULTS: Forty percent (95% CI 35.1-45.0) of women had
      heard about FAS, 16.3% (95% CI 12.8-20.2) knew that folate affects fetal health
      and 5.0% (95% CI 3.1-7.6) knew that it should be taken pre-pregnancy. Level of
      education was strongly associated with awareness (multivariate Odds Ratio for
      lowest vs. highest level of education: 0.29, 95% CI 0.15-0.56). CONCLUSIONS:
      Knowledge of FAS is very low among women of childbearing age in Kathmandu.
      Inclusion of FAS information in health awareness programs is recommended.

PMID- 22975410
TI  - Role of the alternative and classical complement activation pathway in complement
      mediated killing against Streptococcus pneumoniae colony opacity variants during
      acute pneumococcal otitis media in mice.
AB  - There is considerable evidence that phase variation among transparent and opaque
      colony phenotypes of Streptococcus pneumoniae (Spn) plays an important role in
      the pneumococcal adherence and invasion. The current study was designed to
      investigate the interactions of the opacity phenotype variants of Spn with
      specific complement pathway activation in a mouse model of acute otitis media
      (AOM). Although the opaque colony phenotype was expected to be more resistant to
      complement mediated killing compared to the transparent Spn variant, we
      discovered that C3b deposition on the transparent Spn is, in large part,
      dependent on the alternative pathway activation. There were no significant
      differences in resistance to complement mediated opsonophagocytosis between the
      two variants in factor B deficient mice. In addition, an in vitro study
      demonstrated that significantly more C4b-binding protein (C4BP) (the classical
      pathway inhibitor) and factor H (FH) (the alternative pathway inhibitor) bound to
      the transparent strain compared with the opaque one. Our data suggest that the
      difference in the relative virulence of Spn opacity phenotypes is associated with
      its ability to evade complement-mediated opsonophagocytosis in a mouse model of
      pneumococcal AOM.

PMID- 22975412
TI  - Prevalence of metabolic syndrome and factor analysis of cardiovascular risk
      clustering among adolescents in Ho Chi Minh City, Vietnam.
AB  - OBJECTIVE: This study aimed to describe the prevalence of metabolic syndrome
      (MetS) in adolescents of Ho Chi Minh City (HCMC) and to identify components of
      cardiovascular risk clusters. METHODS: A cross-sectional study was conducted on a
      representative sample of 693 high-school students 13 to 16 years old in 2007.
      MetS was defined according to five different definitions: the Pediatric
      International Diabetes Federation, the Adult Treatment Panel III, and the
      modified definitions by Cook, Weiss, and De Ferranti. Principal components
      analysis (PCA) was carried out to cluster risk factors. RESULTS: The prevalence
      of MetS was high and varied from 3.9% to 12.5%, depending on the criteria used.
      High levels of triglycerides (or low High Density Lipoprotein Cholesterol) and
      high blood pressure were the most prevalent components of MetS, while impaired
      glucose tolerance was the least prevalent. PCA showed three factors in boys
      (obesity, hypertension, dyslipidemia) that cumulatively explained 64.3%, and four
      factors in females (obesity, hypertension, dyslipidemia, and hyperglycemia) that
      accounted for 73.6% of the observed variance of MetS. CONCLUSIONS: The prevalence
      of MetS in HCMC adolescents was high. Obesity accounts for the maximum variance
      in clustering and appears to be a more powerful correlate of cardiovascular risk
      than other variables.

PMID- 22975413
TI  - Philosophy and preventive medicine.

PMID- 22975414
TI  - Fabry disease and the clinical spectrum of angiokeratomas.

PMID- 22975415
TI  - Cultural Practices in Immigrant Populations and Their Relevance to Dermatology.

PMID- 22975416
TI  - Mechanisms underlying the antidiarrheal, antispasmodic and bronchodilator
      activities of Fumaria parviflora and involvement of tissue and species
      specificity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the Greco-Arab (Unani) traditional medicine,
      Fumaria parviflora Linn. is widely used in hypreractive gut and respiratory
      disorders including diarrhea, abdominal cramps, indigestion and asthma but
      scientific studies to provide rational for these medicinal uses are sparse. This
      study was therefore undertaken to provide ethnopharmacological basis for its
      medicinal use in diarrhea, abdominal cramps and asthma. MATERIALS AND METHODS:
      The in vivo studies were conducted in mice and rats while isolated gut and
      tracheal preparations of rat, guinea-pig and rabbit were suspended in respective
      tissue baths to measure the isotonic and isometric responses, using Power Lab
      electronic recorder. RESULTS: The aqueous-methanol extract of Fumaria parviflora
      (Fp.Cr) protected against diarrhea caused by castor oil in rats and mice, similar
      to loperamide and dicyclomine, and bronchospasm caused by carbachol (CCh) in
      rats, similar to aminophylline. In the in vitro studies, Fp.Cr relaxed CCh and
      isotonic high K(+) physiological salts solutions-induced contractions in jejunum,
      ileum and tracheal preparations of rat, guinea-pig and rabbit. Fp.Cr was
      predominately more potent against CCh than isotonic high K(+) solutions-induced
      contractions, similar to dicyclomine, suggesting the presence of anticholinergic
      and calcium channel blocking (CCB) activities, which were confirmed when Fp.Cr
      shifted the CCh and Ca(2+) concentration-response curves, constructed in rat
      ileum and trachea, towards right. Among intestinal preparations from various
      species, both anticholinergic and CCB effects of Fp.Cr were exhibited at lower
      concentrations in rat than the other species. In tracheal preparations, Fp.Cr was
      the most potent in its CCB effect in rabbit. Within species, CCB effect of Fp.Cr
      was produced at lower concentrations in rat jejunum than ileum and trachea,
      whereas, anticholinergic effect was produced at higher concentration in rat
      trachea than intestine. CONCLUSION: This study, showing the presence of
      antidiarrheal, antispasmodic and bronchodilator activities in Fumaria parviflora
      possibly mediated through dual blockade of muscarinic receptors and Ca(2+)
      channels, provides sound basis for its medicinal uses in diarrhea, abdominal
      cramps and may be used as bronchodilator in asthma. Species and tissue-dependency
      of these effects underscores the importance of utilizing multiple tissues and
      species to get more meaningful results.

PMID- 22975417
TI  - Ethnobotanical study of plants used in treating hypertension in Edo State of
      Nigeria.
AB  - A study was undertaken in 12 local government areas (LGAs) of Edo State located
      in central southern Nigeria, representing 66.6% coverage, in order to obtain an
      inventory of the major medicinal plants used in folk medicine to treat arterial
      hypertension. One hundred and eighty nine respondents who were mainly traditional
      medical practitioners and were knowledgeable in the medicinal plants for treating
      hypertension were interviewed using semi-structured questionnaire administered by
      trained interviewers. The inventory of medicinal plants is summarized in a
      synoptic table, which contains the scientific, vernacular and common names of the
      plants/frequency of citation, the part of the plant and method of preparation of
      recipes. The study indicated 70 plants belonging to 67 genera in 43 families are
      commonly prescribed. Of these plants, 39 species are cultivated, 29 species grow
      in the wild, while only 2 both grow wild and also cultivated. Ninety three herbal
      antihypertensive recipes are recognized and are mainly prepared as decoctions,
      infusions, powders and juice. The leaf (43%) represented the dominant
      morphological part often included in recipes. Plants frequently included in
      antihypertensive recipes were Allium species, Persea americana, Acalypha
      godseffiana, Zingiber officinale, Sida acuta, Hunteria umbellata, Rauwolfia
      vomitoria, Viscum album and Aframomum melegueta.

PMID- 22975418
TI  - Effect of partial crystallization on the mechanical properties and cytotoxicity
      of bioactive glass from the 3CaO.P(2)O(5)-SiO(2)-MgO system.
AB  - The aim of this study is to report on the development and characterization of
      bioactive glass and glass-ceramics from the 3CaO.P(2)O(5)-SiO(2)-MgO-system,
      using different degrees of cristallinity for applications as an implant material.
      A methodology was proposed to induce crystallization of phases. Bioglass samples
      of the nominal composition (wt %) 57.75 CaO.P(2)O(5)-30 SiO(2)-17.25MgO were heat
      treated at temperatures ranging from 700 to 1100 degrees C for 4h. The findings
      from the research illustrate how partial crystallization and phase
      transformations modified the microstructure of the based glassy material,
      resulting in improved mechanical properties. The maximum gain was measured for
      samples treated at 975 degrees C, having a hardness of 6.2GPa, an indentation
      fracture toughness of 1.7MPam(1/2) and a bending strength of 120MPa, representing
      an increase of 30, 55 and 70%, respectively, when compared to the nucleated
      glass. The highest elastic modulus of about 130GPa was determined for samples
      treated at 1100 degrees C. As a preliminary biological evaluation, "in vitro"
      cytotoxicity tests were realized to determine the cytotoxic level of the
      materials, using the neutral red uptake method with NCTC clones L929 from the
      American Type Culture Collection (ATCC) bank. On the other hand, no significant
      influence of the partial crystallization on cytotoxicity was observed. The
      results provide support for implant materials based on the 3CaO.P(2)O(5)-SiO(2)
      MgO-system.

PMID- 22975419
TI  - Architectural design and physical activity: an observational study of staircase
      and elevator use in different buildings.
AB  - BACKGROUND: The indoor built environment has the potential to influence levels of
      physical activity. However, the extent to which architectural design in
      commercial buildings can influence the percentage of people choosing to use the
      stairs versus elevators is unknown. The purpose of this study was to determine if
      buildings with centrally located, accessible, and aesthetically pleasing
      staircases result in a greater percentage of people taking the stairs. METHODS:
      Direct observations of stair and elevator use were conducted in 3 buildings on a
      university campus. One of the buildings had a bank of 4 centrally located
      elevators and a fire escape stairwell behind a steel door. The other 2 buildings
      had centrally located staircases and out-of-the-way elevators. RESULTS: The
      percentage of people who ascended the stairs was 8.1% in the elevator-centric
      building, compared with 72.8% and 81.1% in the 2 stair-centric buildings (P <
      .001). In addition, the percentage of people who descended the stairs was 10.8%
      in the first building, compared with 89.5% and 93.7% in the stair-centric
      buildings (P < .001). CONCLUSIONS: The results of the current study suggest that
      if buildings are constructed with centrally located, accessible, and
      aesthetically pleasing staircases, a greater percentage of people will choose to
      take the stairs.

PMID- 22975420
TI  - SUMO1 modulates Abeta generation via BACE1 accumulation.
AB  - Accumulation of disease-related proteins is a characteristic event observed in
      the pathogenesis of neurodegenerative diseases. beta-secretase (BACE)-1, which
      initiates generation of beta-amyloid (Abeta), is increased in the Alzheimer's
      diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's
      disease are largely unknown. In this report, we found that small ubiquitin-like
      modifier (SUMO)-1 interacts with the dileucine motif of BACE1 and regulates the
      level of BACE1 protein. This was proved by the coimmunoprecipitation, and gain or
      loss of function experiments. Altering 3 SUMO isoforms affects BACE1 protein
      levels, and consequently results in altered amyloid precursor protein processing
      and Abeta generation. BACE1 levels were increased in response to Abeta or
      apoptosis, but not in cells lacking SUMO1. Abeta increased SUMO1 protein levels
      in rat cortical neurons. Moreover, SUMO1 immunoreactivity was increased in the
      amyloid precursor protein transgenic mice. Furthermore, the C-terminus fragments
      of BACE1 containing dileucine motif reduced Abeta generation by SUMO1
      overexpression. Our study indicates SUMO1 is not only a novel and potent
      regulator of BACE1 accumulation and Abeta generation but also a potential
      therapeutic target for Alzheimer's disease.

PMID- 22975421
TI  - Apicobasal gradient of left ventricular myocardial edema underlies transient T
      wave inversion and QT interval prolongation (Wellens' ECG pattern) in Tako-Tsubo
      cardiomyopathy.
AB  - BACKGROUND: Tako-Tsubo cardiomyopathy (TTC) presents with chest pain, ST-segment
      elevation followed by T-wave inversion and QT interval prolongation (Wellens'
      electrocardiographic [ECG] pattern), and left ventricular dysfunction, which may
      mimic an acute coronary syndrome. OBJECTIVE: To assess the pathophysiologic basis
      of the Wellens' ECG pattern in TTC by characterization of underlying myocardial
      changes by using cardiac magnetic resonance (CMR). METHODS: The study population
      included 20 consecutive patients with TTC (95% women; mean age 65.3 +/- 10.4
      years) who underwent CMR studies both in the initial phase and after 3-month
      follow-up by using a protocol that included cine images, T2-weighted sequences
      for myocardial edema, and post-contrast sequences for late gadolinium
      enhancement. Quantitative ECG indices of repolarization, such as maximal
      amplitude of negative T waves, sum of the amplitudes of negative T waves, and
      maximum corrected QT interval (QTc max), were correlated to CMR findings.
      RESULTS: At the time of initial CMR study, there was a significant linear
      correlation between the apicobasal ratio of T2-weighted signal intensity for
      myocardial edema and the maximal amplitude of negative T waves (rho = 0.498; P =
      .02), sum of the amplitudes of negative T waves (rho = 0.483; P = .03), and
      maximum corrected QT interval (rho = 0.520; P = .02). Repolarization indices were
      unrelated to either late gadolinium enhancement or quantitative cine parameters.
      Wellens' ECG abnormalities and myocardial edema showed a parallel time course of
      development and resolution on initial and follow-up CMR studies. CONCLUSIONS: Our
      study results show that the ischemic-like Wellens' ECG pattern in TTC coincides
      and quantitatively correlates with the apicobasal gradient of myocardial edema as
      evidenced by using CMR. Dynamic negative T waves and QTc prolongation are likely
      to reflect the edema-induced transient inhomogeneity and dispersion of
      repolarization between apical and basal left ventricular regions.

PMID- 22975422
TI  - Increased risk of parkinsonism associated with welding exposure.
AB  - OBJECTIVE: Manganese (Mn), an established neurotoxicant, is a common component of
      welding fume. The neurological phenotype associated with welding exposures has
      not been well described. Prior epidemiologic evidence linking occupational
      welding to parkinsonism is mixed, and remains controversial. METHODS: This was a
      cross-sectional and nested case-control study to investigate the prevalence and
      phenotype of parkinsonism among 811 shipyard and fabrication welders recruited
      from trade unions. Two reference groups included 59 non-welder trade workers and
      118 newly diagnosed, untreated idiopathic PD patients. Study subjects were
      examined by a movement disorders specialist using the Unified Parkinson Disease
      Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as
      welders with UPDRS3 score >=15. Normal was defined as UPDRS3<6. Exposure was
      classified as intensity adjusted, cumulative years of welding. Adjusted
      prevalence ratios for parkinsonism were calculated in relation to quartiles of
      welding years. RESULTS: The overall prevalence estimate of parkinsonism was 15.6%
      in welding exposed workers compared to 0% in the reference group. Among welders,
      we observed a U-shaped dose-response relation between weighted welding exposure
      years and parkinsonism. UPDRS3 scores for most domains were similar between
      welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except
      for greater frequency of rest tremor and asymmetry in PD patients. CONCLUSION:
      This work-site based study among welders demonstrates a high prevalence of
      parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that
      overlaps substantially with PD.

PMID- 22975423
TI  - Manganese mixture inhalation is a reliable Parkinson disease model in rats.
AB  - Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it
      has been reported that the overexposure causes neurotoxicity manifested as
      extrapyramidal symptoms similar to those observed in Parkinson disease (PD).
      Recently, our group reported that mice that inhaled for 5 months the mixture of
      manganese chloride (MnCl(2)) and manganese acetate Mn(OAc)(3) developed movement
      abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic
      neurons, dopamine depletion and improved behavior with l-DOPA treatment. However,
      this model has only been characterized in mice. In order to have a well-supported
      and generalizable model in rodents, we used male Wistar rats that inhaled a
      mixture of 0.04 M MnCl(2) and 0.02 M Mn(OAc)(3), 1h three times a week for 6
      months. Before Mn exposure, animals were trained to perform motor tests (Beam
      walking and Single-pellet reaching tasks) and were evaluated each week after the
      exposure. The mixture of MnCl(2)/Mn(OAc)(3) caused alterations in the motor
      tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus
      Pallidus or striatum. With these results we conclude that the inhalation of the
      mixture of Mn compounds is a useful model in rodents for the study of PD.

PMID- 22975425
TI  - Molecular simulation of flavin adenine dinucleotide immobilized on charged single
      walled carbon nanotubes for biosensor applications.
AB  - The reconstitution of apo-glucose oxidase (apo-GOx) on single-walled carbon
      nanotubes (SWNTs) functionalized with the cofactor, flavin adenine dinucleotide
      (FAD), greatly improved electron transfer turnover rate of the redox reactions in
      glucose sensing with glucose sensors. The research reported here is aimed to
      better understand molecular details of affection of the charging SWNT to the
      conformational changes of FAD, in order to find a rational design and selection
      scheme of SWNT which is suitable for the FAD and apo-GOx to perform their
      reconstitution. In this report, molecular simulations of FAD functionalized
      differently charged SWNTs were carried outin an aqueous environment, with
      counterions to maintain total charge neutrality. The conformation and orientation
      changes were observed by both trajectory and quantitative analyses. The
      simulation results showed that in both uncharged and positively charged SWNT
      situations, FAD adsorbed onto SWNT at the end of the simulations, which increased
      the steric resistance of molecules and hindered the reconstitution of apo-GOx and
      FAD to some degree. By contrast, FAD functionalized negatively charged SWNT
      maintained its original conformation largely. In addition, negatively charged
      SWNT may be the best choice for electron transfer mediator for the reconstitution
      of apo-GOx on relay-cofactor units associated with electrodes.

PMID- 22975426
TI  - The role of osmotic polysorbitol-based transporter in RNAi silencing via caveolae
      mediated endocytosis and COX-2 expression.
AB  - Polymeric diversity allows us to design gene carriers as an alternative to viral
      vectors, control cellular uptake, target intracellular molecules, and improve
      transfection and silencing capacity. Recently, we developed a polysorbitol-based
      osmotically active transporter (PSOAT), which exhibits several interesting
      mechanisms to accelerate gene delivery into cells. Herein, we report the efficacy
      of using the PSOAT system for small interfering RNA (siRNA) delivery and its
      specific mechanism for cellular uptake to accelerate targeted gene silencing. We
      found that PSOAT functioned via a caveolae-mediated uptake mechanism due to
      hyperosmotic activity of the transporter. Moreover, this selective caveolae
      mediated endocytosis of the polyplexes (PSOAT/siRNA) was regulated coincidently
      with the expression of caveolin (Cav)-1 and cyclooxygenase (COX)-2.
      Interestingly, COX-2 expression decreased dramatically over time due to
      degradation by the constant expression of Cav-1, as confirmed by high COX-2
      expression after the inhibition of Cav-1, suggesting that PSOAT-mediated
      induction of Cav-1 directly influenced the selective caveolae-mediated
      endocytosis of the polyplexes. Furthermore, COX-2 expression was involved in the
      initial phase for rapid caveolae endocytic uptake of the particles
      synergistically with Cav-1, resulting in accelerated PSOAT-mediated target gene
      silencing.

PMID- 22975424
TI  - Magnetic resonance imaging and volumetric analysis: novel tools to study the
      effects of thyroid hormone disruption on white matter development.
AB  - Humans and wildlife are exposed to environmental pollutants that have been shown
      to interfere with the thyroid hormone system and thus may affect brain
      development. Our goal was to expose pregnant rats to propylthiouracil (PTU) to
      measure the effects of a goitrogen on white matter development in offspring using
      magnetic resonance imaging (MRI) and volumetric analysis. We exposed pregnant
      Sprague Dawley (SD) rats to 3 or 10 ppm PTU from gestation day 7 (GD7) until
      postnatal day 25 (P25) to determine the effects on white matter (WM), gray matter
      (GM), and hippocampus volumes in offspring. We sacrificed offspring at P25 but
      continued the life of some offspring to P90 to measure persistent effects in
      adult animals. P25 offspring exposed to 10 ppm PTU displayed lowered levels of
      triiodothyronine (T3) and thyroxine (T4); cerebral WM, GM, and total brain
      volumes were significantly lower than the volumes in control animals. P90 adults
      exposed to 10 ppm PTU displayed normal T3 levels but lowered T4 levels; WM, GM,
      total brain, and hippocampal volumes were significantly lower than the volumes in
      control adults. Both P25 and P90 rats exposed to 10 ppm PTU displayed significant
      reductions in percent WM as well as heterotopias in the corpus callosum. Exposure
      to 3 ppm PTU did not produce any significant effects. These results suggest that
      MRI coupled with volumetric analysis is a powerful tool in assessing the effects
      of thyroid hormone disruption on white matter development and brain structure.
      This approach holds great promise in assessing neurotoxicity of xenobiotics in
      humans and wildlife.

PMID- 22975427
TI  - The use of polyion complex micelles to enhance the oral delivery of salmon
      calcitonin and transport mechanism across the intestinal epithelial barrier.
AB  - The objective of the present study was to demonstrate the effect of polyanionic
      copolymer mPEG-grafted-alginic acid (mPEG-g-AA)-based polyion complex (PIC)
      micelles on enhancing the oral absorption of salmon calcitonin (sCT) in vivo and
      in vitro and identify the transepithelial transport mechanism of PIC micelles
      across the intestinal barrier. mPEG-g-AA was first successfully synthesized and
      characterized in cytotoxicity. The PIC micelles were approximately of 72 nm in
      diameter with a narrow distribution. The extremely significant enhancement of
      hypocalcemia efficacy of sCT-loaded PIC micelles in rats was evidenced by
      intraduodenal administration in comparison with sCT solution. The presence of
      mPEG-grafted-chitosan in PIC micelles had no favorable effect on this action in
      the referred content. In the Caco-2 transport studies, PIC micelles could
      significantly increase the permeability of sCT across Caco-2 monolayers without
      significantly affecting transepithelial electrical resistance values during the
      transport study. No evident alterations in the F-actin cytoskeleton were detected
      by confocal microscope observation following treatment of the cell monolayers
      with PIC micelles, which further certified the incapacity of PIC micelles to open
      the intercellular tight junctions. In addition, TEM observations showed that the
      intact PIC micelles were transported across the everted gut sac. These suggested
      that the transport of PIC micelles across Caco-2 cell monolayers involve a
      predominant transcytosis mechanism via endocytosis rather than paracellular
      pathway. Furthermore, PIC micelles were localized in both the cytoplasm and the
      nuclei observed by CLSM. Therefore, PIC micelles might be a potentially
      applicable tool for enhancing the oral absorption of cationic peptide and protein
      drugs.

PMID- 22975428
TI  - Treatment technique evolution and dosimetry trends over seven years of low dose
      rate prostate brachytherapy at an Australian institution.
AB  - Low dose rate prostate brachytherapy treatments began at the Royal Adelaide
      Hospital (RAH), Australia, in September 2004. This paper will focus on the
      evolution of treatment technique since then showing how procedural improvements
      have enabled timely diagnosis of under-dose and scheduling of top-up treatments
      for sub-optimum implants, and how significant time savings have been achieved for
      staff and patients. In addition, implant dosimetry trends over this period have
      been investigated and results are presented. Iodine-125 seeds (Oncura model 6711)
      have been used since LDR prostate treatments began, with an aim to deliver a
      prostate dose of 145 Gy. Three key changes in implant technique took place during
      the period Sept 2004 to Sept 2011. The live implant dosimetry trends of the
      prostate D90, urethra V150, and rectum D0.1cc and D2.0cc, were assessed to see if
      the change in technique had an impact on the treatment planning and seed
      deployment. The switch from manual loading of seeds to pre-loaded needles and the
      change from a two-step pre-planning procedure to live planning have realized the
      greatest time savings with approximately 1.0 FTE physicist day saved per 2
      patient implant day and 2 patient visits saved per treatment. Dosimetric
      parameters also improved with mean implant D90s rising from 166 Gy to 180 Gy. The
      average Urethra D10 also increased over the study group, rising from 186 Gy to
      199 Gy while the rectum dose remained unchanged. Both rectum and urethra dose
      remained below GEC-ESTRO guidelines despite the observed rise in urethral dose. 

PMID- 22975429
TI  - Prediction methods for synchronization of scanned ion beam tracking.
AB  - Beam tracking as a mitigation technique for treatment of intra-fractionally
      moving organs requires prediction to overcome latencies in the adaptation
      process. We implemented and experimentally tested a prediction method for scanned
      carbon beam tracking. Beam tracking parameters, i.e. the shift of the Bragg peak
      position in 3D, are determined prior to treatment in 4D treatment planning and
      applied during treatment delivery in dependence on the motion state of the target
      as well as on the scanning spot in the target. Hence, prediction is required for
      the organ motion trajectory as well as the scanning progress to achieve maximal
      performance. Prediction algorithms to determine beam displacements that overcome
      these latencies were implemented. Prediction times of 25 ms for target spot
      prediction were required for ~6 mm water-equivalent longitudinal beam shifts. The
      experimental tests proved feasibility of the implemented prediction algorithm.

PMID- 22975430
TI  - Combined PET/CT for IMRT treatment planning of NSCLC: contrast-enhanced CT images
      for Monte Carlo dose calculation.
AB  - PURPOSE: Combined PET/CT imaging has been proposed as an integral part of
      radiotherapy treatment planning (TP). Contrast-enhanced CT (ceCT) images are
      frequently acquired as part of the PET/CT examination to support target
      delineation. The aim of this dosimetric planning study was to investigate the
      error introduced by using a ceCT for intensity modulated radiotherapy (IMRT) TP
      with Monte Carlo dose calculation for non-small cell lung cancer (NSCLC).
      MATERIAL AND METHODS: Nine patients with NSCLC prior to chemo-RT were included in
      this retrospective study. For each patient non-enhanced, low-dose CT (neCT), ceCT
      and [(18)F]-FDG-PET emission data were acquired within a single examination.
      Manual contouring and TP were performed on the ceCT. An additional set of
      independent target volumes was auto-segmented in PET images. Dose distributions
      were recalculated on the neCT. Differences in dosimetric parameters were
      evaluated. RESULTS: Dose differences in PTV and lungs were small for all
      patients. The maximum difference in all PTVs when using ceCT images for dose
      calculation was -2.1%, whereas the mean difference was less than -1.7%. Maximum
      differences in the lungs ranged from -1.8% to 2.1% (mean: -0.1%). In four
      patients an underestimation of the maximum spinal cord dose between 2% and 3.2%
      was observed, but treatment plans remained clinically acceptable. CONCLUSIONS:
      Monte Carlo based IMRT planning for NSCLC patients using ceCT allows for correct
      dose calculation. A direct comparison to neCT-based treatment plans revealed only
      small dose differences. Therefore, ceCT-based TP is clinically safe as long as
      the maximum acceptable dose to organs at risk is not approached.

PMID- 22975431
TI  - Fast simulation of x-ray projections of spline-based surfaces using an append
      buffer.
AB  - Many scientists in the field of x-ray imaging rely on the simulation of x-ray
      images. As the phantom models become more and more realistic, their projection
      requires high computational effort. Since x-ray images are based on transmission,
      many standard graphics acceleration algorithms cannot be applied to this task.
      However, if adapted properly, the simulation speed can be increased dramatically
      using state-of-the-art graphics hardware. A custom graphics pipeline that
      simulates transmission projections for tomographic reconstruction was implemented
      based on moving spline surface models. All steps from tessellation of the
      splines, projection onto the detector and drawing are implemented in OpenCL. We
      introduced a special append buffer for increased performance in order to store
      the intersections with the scene for every ray. Intersections are then sorted and
      resolved to materials. Lastly, an absorption model is evaluated to yield an
      absorption value for each projection pixel. Projection of a moving spline
      structure is fast and accurate. Projections of size 640 * 480 can be generated
      within 254 ms. Reconstructions using the projections show errors below 1 HU with
      a sharp reconstruction kernel. Traditional GPU-based acceleration schemes are not
      suitable for our reconstruction task. Even in the absence of noise, they result
      in errors up to 9 HU on average, although projection images appear to be correct
      under visual examination. Projections generated with our new method are suitable
      for the validation of novel CT reconstruction algorithms. For complex
      simulations, such as the evaluation of motion-compensated reconstruction
      algorithms, this kind of x-ray simulation will reduce the computation time
      dramatically.

PMID- 22975433
TI  - The role of the sexual assault centre.
AB  - Sexual Assault Centres provide multidisciplinary care for men and women who have
      experienced sexual crime. These centres enable provision of medical, forensic,
      psychological support and follow-up care, even if patients chose not to report
      the incident to the police service. Sexual Support Centres need to provide a ring
      fenced, forensically clean environment. They need to be appropriately staffed and
      available 24 hours a day, 7 days a week to allow prompt provision of medical and
      supportive care and collection of forensic evidence. Sexual Assault Centres work
      best within the context of a core agreed model of care, which includes defined
      multi-agency guidelines and care pathways, close links with forensic science and
      police services, and designated and sustainable funding arrangements.
      Additionally, Sexual Assault Centres also participate in patient, staff and
      community education and risk reduction. Furthermore, they contribute to the
      development, evaluation and implementation of national strategies on domestic,
      sexual and gender-based violence.

PMID- 22975432
TI  - Health consequences of sexual violence against women.
AB  - Sexual violence can lead to a multitude of health consequences, including
      physical, reproductive and psychological. Some may be fatal, whereas others, such
      as unhealthy behaviours, may occur indirectly as a result of the violence. In
      total, these result in a significant health burden and should be considered by
      service providers, government authorities and non-governmental agencies. For
      women who present early, immediate care should be provided with plans for follow
      up. Mental-health interventions are important, as women who are sexually
      assaulted have the highest burden of post-traumatic stress disorder. Cognitive-
      behavioural therapy has been found to be effective for preventing and treating
      post-traumatic stress disorder, but psychological debriefing for preventing post
      traumatic stress disorder is not recommended. Implementing a routine screening
      and intervention programme in obstetrics and gynaecology departments may be
      valuable, as reproductive health consequences are common.

PMID- 22975434
TI  - The role of orthography and phonology in English: an ERP study on first and
      second language reading aloud.
AB  - This study investigated the role of orthographic and phonological information in
      reading aloud. Dutch-English bilinguals (L2) and native English (L1) participants
      read aloud English words. The contribution of orthographic and phonological
      activation was distinguished with prime manipulation. Phonological overlap, but
      not orthographic overlap, facilitated the response latencies for both English L1
      and L2 speakers. In contrast, event-related brain potentials also revealed
      orthographic priming for both groups. Altogether, the present results demonstrate
      that late L2 speakers exhibit a Masked Onset Priming Effect similar to that of
      native speakers. In addition, the ERP results revealed that orthographic
      information is activated earlier during reading, but is not detectable anymore at
      the behavioral response level when the task is reading aloud.

PMID- 22975435
TI  - Connexin and pannexin hemichannels in inflammatory responses of glia and neurons.
AB  - Mammals express ~20 different connexins, the main gap junction forming proteins
      in mammals, and 3 pannexins, homologs of innexins, the main gap junction forming
      proteins in invertebrates. In both classes of gap junction, each channel is
      formed by two hemichannels, one contributed by each of the coupled cells. There
      is now general, if not universal, agreement that hemichannels of both classes can
      open in response to various physiological and pathological stimuli when they are
      not apposed to another hemichannels and face the external milieu. Connexin (and
      likely pannexin) hemichannel permeability is consistent with that of the cell
      cell channels and open hemichannels can be a release site for relatively large
      molecules such as ATP and glutamate, which can serve as transmitters between
      cells. Here we describe three experimental paradigms in which connexin and
      pannexin hemichannel signaling occurs. (1) In cultures of spinal astrocytes FGF-1
      causes the release of ATP, and ATP causes opening of pannexin hemichannels, which
      then release further ATP. Subsequently, several hours later, connexin
      hemichannels are also opened by an unknown mechanism. Release of ATP appears to
      become self sustaining through action of P2X7 receptors to open pannexin
      hemichannels and then connexin hemichannels, both of which are ATP permeable. (2)
      Spinal cord injury by dropping a small weight on the exposed cord is followed by
      release of ATP in the region surrounding the primary lesion. This release is
      greatly reduced in a mouse in which Cx43 is knocked down in the astrocytes.
      Application of FGF-1 causes a similar release of ATP in the uninjured spinal
      cord, and an inhibitor of the FGF-1 receptor, PD173074, inhibits both FGF-1 and
      injury-induced release. Reduction in ATP release is associated with reduced
      inflammation and less secondary expansion of the lesion. (3) Cortical astrocytes
      in culture are permeabilized by hypoxia, and this effect is increased by high or
      zero glucose. The mechanism of permeabilization is opening of Cx43 hemichannels,
      which can lead to cell death. Activated microglia secrete TNF-alpha and IL-1beta,
      which open connexin hemichannels in astrocytes. Astrocytes release ATP and
      glutamate which can kill neurons in co-culture through activation of neuronal
      pannexin hemichannels. These studies implicate two kinds of gap junction
      hemichannel in inflammatory responses and cell death. This article is part of a
      Special Issue entitled Electrical Synapses.

PMID- 22975437
TI  - Behavioral changes after maternal separation are reversed by chronic constant
      light treatment.
AB  - BACKGROUND: Rats subjected to maternal separation display behavioral alterations
      (e.g. increased immobility in the forced swim test) and molecular changes (e.g.
      in growth factors and related signal transduction proteins). Light treatment has
      previously been shown to have antidepressant effects in rat models of depression,
      but has not been studied in a rodent model of maternal separation. METHODS: This
      study focused on maternally separated rat pups. The aim of this study was to
      compare the effects of chronic constant light exposure during adolescence with
      the selective serotonin reuptake inhibitor (SSRI), escitalopram. Behavioral
      changes (exploratory activity in the open field and elevated plus maze, 22 kHz
      ultrasonic vocalizations, immobility in the forced swim test) and molecular
      changes (brain-derived neurotrophic factor (BDNF), mitogen-activated protein
      kinase phosphatase-1 (MKP-1) in the ventral hippocampus, and mu-opioid receptors
      in the nucleus accumbens) were measured. RESULTS: Animals that had been subjected
      to maternal separation displayed an increased number and duration of 22 kHz
      vocalizations, increased immobility in the forced swim test, increased
      hippocampal BDNF, and decreased mu-opioid receptor levels in the nucleus
      accumbens in adulthood compared to controls. MKP-1 levels in the ventral
      hippocampus were not affected. After chronic light treatment, there was
      normalization of ultrasonic vocalizations, immobility on the forced swim test,
      and mu-opioid receptor levels in the nucleus accumbens. Chronic saline treatment
      reduced anxiety-like behavior and immobility in the forced swim test.
      Escitalopram did not have any significant effect in this rat model of depression.
      CONCLUSION: Chronic constant light treatment reversed a number of the behavioral
      and molecular effects of maternal separation. Light-induced up-regulation of mu
      opioid receptors in the nucleus accumbens may play a key role in mediating such
      effects.

PMID- 22975436
TI  - Pregnancy affects FOS rhythms in brain regions regulating sleep/wake state and
      body temperature in rats.
AB  - Circadian rhythms in behavior and physiology change substantially as female
      mammals undergo the transition from a non-pregnant to a pregnant state. Here, we
      examined the possibility that site-specific changes in brain regions known to
      regulate the sleep/wake cycle and body temperature might reflect altered rhythms
      in these overt functions. Specifically, we compared daily patterns of
      immunoreactive FOS in early pregnant and diestrous rats in the medial septum
      (MS), vertical and horizontal diagonal bands of Broca (VDB and HDB), perifornical
      lateral hypothalamus (LH), and ventrolateral, medial, and median preoptic areas
      (VLPO, MPA, and MnPO, respectively). In the pregnant animals, FOS expression was
      reduced and the daily rhythms of expression were lost or attenuated in the MS,
      VDB, and LH, areas known to support wakefulness, and in the MPA, a brain region
      that may coordinate sleep/wake patterns with temperature changes. However,
      despite the well-documented differences in sleep patterns between diestrous and
      pregnant rats, reproductive state did not affect FOS expression in the VLPO or
      MnPO, two brain regions in which FOS expression usually correlates with sleep.
      These data indicate that plasticity in sleep/wake patterns during early pregnancy
      may be driven by a reduction in wakefulness-promotion by the brain, rather than
      by an increase in sleep drive.

PMID- 22975439
TI  - Clinical endpoint adjudication in a contemporary all-comers coronary stent
      investigation: methodology and external validation.
AB  - BACKGROUND: Globalisation in coronary stent research calls for harmonization of
      clinical endpoint definitions and event adjudication. Little has been published
      about the various processes used for event adjudication or their impact on
      outcome reporting. METHODS AND RESULTS: We performed a validation of the clinical
      event committee (CEC) adjudication process on 100 suspected events in the
      RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research
      Organisations (CRO) that had already extensive internal validation processes in
      place, participated in the study. After initial adjudication by the primary-CEC,
      events were cross-adjudicated by an external-CEC using the same definitions.
      Major discrepancies affecting the primary end point of target-lesion failure
      (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI),
      or clinically-indicated target-lesion revascularization (CI-TLR), were analysed
      by an independent oversight committee who provided recommendations for
      harmonization. Discordant adjudications were reconsidered by the primary CEC.
      Subsequently, the RAC database was interrogated for cases that based on these
      recommendations merited re-adjudication and these cases were also re-adjudicated
      by the primary CEC. Final discrepancies in adjudication of individual components
      of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the
      (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV
      MI). After application of harmonization recommendations to the overall RAC
      population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and
      considered 1 TV-MI as no event. CONCLUSIONS: A harmonization process provided a
      high level of concordance for event adjudication and improved accuracy for final
      event reporting. These findings suggest it is feasible to pool clinical event
      outcome data across clinical trials even when different CECs are responsible for
      event adjudication.

PMID- 22975440
TI  - The toxic effects of diethyl phthalate on the activity of glutamine synthetase in
      greater duckweed (Spirodela polyrhiza L.).
AB  - The toxic effects of diethyl phthalate (DEP), a potent allelochemical, on the
      enzyme activity and polypeptide accumulation of glutamine synthetase (GS) in
      greater duckweed were investigated. In our previous studies, DEP induced
      oxidative responses at concentrations from 0.5 to 2 mM in greater duckweed and
      the antioxidant enzymes played important roles in the defense strategy against
      DEP stress. In this study, DAB-H(2)O(2) and NBT stain for superoxide radicals
      (O(2)(.-)), lipid peroxidation, HSP70, and ammonia accumulation in DEP-treated
      duckweed tissues revealed adverse effect of DEP in plant growth. Biochemical
      analysis and physiological methods were combined to investigate GS activity and
      polypeptide accumulation under DEP-induced stress. The results showed that GS
      activity was reduced with the increasing concentration of DEP, indicative of
      enhanced toxic effect. Immunoblot analysis with chloroplast soluble fractions
      indicated that the chloroplastic GS (GS2) polypeptide from greater duckweed was
      degraded under DEP stress conditions. The response of GS2 to the DEP stress may
      be modulated by means of redox change in plant tissues, chloroplasts, and
      chloroplast lysates. The results suggest that DEP is toxic to the greater
      duckweed by inhibition of the GS isoenzymes in nitrogen assimilation and the GS2
      plays important roles in the adaptation strategy against DEP toxicity.

PMID- 22975441
TI  - Polycyclic aromatic hydrocarbons and dibutyl phthalate disrupt dorsal-ventral
      axis determination via the Wnt/beta-catenin signaling pathway in zebrafish
      embryos.
AB  - The canonical Wnt/beta-catenin signaling pathway is critical during early teleost
      development for establishing the dorsal-ventral axis. Within this pathway, GSK
      3beta, a key regulatory kinase in the Wnt pathway, regulates beta-catenin
      degradation and thus the ability of beta-catenin to enter nuclei, where it can
      activate expression of genes that have been linked to the specification of the
      dorsal-ventral axis. In this study, we describe the morphological abnormalities
      that resulted in zebrafish embryos when axis determination was disrupted by
      environmental contaminants. These abnormalities were linked to abnormal nuclear
      accumulation of beta-catenin. Furthermore, we demonstrated that the developmental
      abnormalities and altered nuclear beta-catenin accumulation occurred when embryos
      were exposed to commercial GSK-3beta inhibitors. Zebrafish embryos were exposed
      to commercially available GSK-3 inhibitors (GSK-3 Inhibitor IX and 1
      azakenpaullone), or common environmental contaminants (dibutyl phthalate or the
      polycyclic aromatic hydrocarbons phenanthrene and fluorene) from the 2 to 8-cell
      stage through the mid-blastula transition (MBT). These embryos displayed
      morphological abnormalities at 12.5 h post-fertilization (hpf) that were
      comparable to embryos exposed to lithium chloride (LiCl) (300 mM LiCl for 10 min,
      prior to the MBT), a classic disruptor of embryonic axis determination. Whole
      mount immunolabeling and laser scanning confocal microscopy were used to localize
      beta-catenin. The commercial GSK-3 Inhibitors as well as LiCl, dibutyl phthalate,
      fluorene and phenanthrene all induced an increase in the levels of nuclear beta
      catenin throughout the embryo, indicating that the morphological abnormalities
      were a result of disruption of Wnt/beta-catenin signaling during dorsal-ventral
      axis specification. The ability of environmental chemicals to directly or
      indirectly target GSK-3beta was assessed. Using Western blot analysis, the
      ability of these chemicals to affect enzymatic inhibitory phosphorylation at
      serine 9 on GSK-3beta was examined, but no change in the serine phosphorylation
      state of GSK-3beta was detected in exposed embryos. Furthermore, polycyclic
      aromatic hydrocarbons and dibutyl phthalate had no direct effect on the in vitro
      kinase activity of GSK-3beta. While developmental abnormalities resulting from
      these axis-disrupting contaminants were linked to beta-catenin accumulation in
      nuclei, the details of the disruption of this signaling pathway remain unknown.
      Since phenanthrene and fluorene as well as other hydrocarbons have been shown to
      disrupt axial development in sea urchin embryos, and since axis determination and
      the Wnt/beta-catenin signaling pathway are highly conserved, we propose that
      these environmental contaminants may impact embryo development through a similar
      mechanism across phyla.

PMID- 22975438
TI  - Intra-accumbal administration of shRNAs against CART peptides cause increases in
      body weight and cocaine-induced locomotor activity in rats.
AB  - In order to examine the effect of cocaine and amphetamine regulated transcript
      (CART) peptide depletion in adult rats, CART shRNAs or scrambled control shRNAs
      were administered bilaterally into the nucleus accumbens (NAc). There was an
      increase in body weight of the shRNA injected rats compared with the rats
      injected with the scrambled RNA. This is compatible with the data showing a role
      for the peptide in body weight and food intake. Also at this time, there was
      about a two-and-a-half fold increase in cocaine-mediated locomotion in the shRNA
      injected rats compared to the control rats. This finding is critical support for
      the hypothesis that endogenous CART peptides in the NAc inhibit the actions of
      cocaine and other psychostimulants. In immunohistochemical experiments on these
      same animals, there was a decrease in the staining density of CART peptide in the
      NAc of the shRNA injected rats. These data show that shRNA can reduce CART
      peptides in the NAc and that endogenous CART peptides influence body weight and
      cocaine-induced locomotor activity (LMA).

PMID- 22975442
TI  - The subthalamic nucleus is involved in successful inhibition in the stop-signal
      task: a local field potential study in Parkinson's disease.
AB  - Normal actions and behaviors often require inhibition of unwanted and inadequate
      movements. Motor inhibition has been studied using the stop signal task, in which
      participants are instructed to respond to a go signal. Sporadically, a stop
      signal is also delivered after a short interval following the go signal,
      prompting participants to inhibit their already started response to the go
      signal. Functional MRI studies using this paradigm have implicated the activation
      of the subthalamic nucleus in motor inhibition. We directly recorded subthalamic
      nucleus activity from bilaterally implanted deep brain stimulation electrodes in
      a group of 10 patients with Parkinson's disease, during performance of the stop
      signal task. Response inhibition was associated with specific changes in
      subthalamic activity in three different frequency bands. Response preparation was
      associated with a decrease in power and cortico-subthalamic coherence in the beta
      band (12-30 Hz), which was smaller and shorter when the response was successfully
      inhibited. In the theta band, we observed an increase in frontal cortico
      subthalamic coherence related to the presence of the stop signal, which was
      highest when response inhibition was unsuccessful. Finally, a specific
      differential pattern of gamma activity was observed in the "on" motor state.
      Performance of the response was associated with a significant increase in power
      and cortico-subthalamic coherence, while successful inhibition of the response
      was associated with a bilateral decrease in subthalamic power and cortico
      subthalamic coherence. Importantly, this inhibition-related decrease in gamma
      activity was absent in the four patients with dopamine-agonist related impulse
      control disorders. Our results provide direct support for the involvement of the
      subthalamic nucleus in response inhibition and suggest that this function may be
      mediated by a specific reduction in gamma oscillations in the cortico-subthalamic
      connection.

PMID- 22975443
TI  - Epigenetic inheritance and plasticity: The responsive germline.
AB  - Developmental plasticity, the capacity of a single genotype to give rise to
      different phenotypes, affects evolutionary dynamics by influencing the rate and
      direction of phenotypic change. It is based on regulatory changes in gene
      expression and gene products, which are partially controlled by epigenetic
      mechanisms. Plasticity involves not just epigenetic changes in somatic cells and
      tissues; it can also involve changes in germline cells. Germline epigenetic
      plasticity increases evolvability, the capacity to generate heritable,
      selectable, phenotypic variations, including variations that lead to novel
      functions. I discuss studies that show that some complex adaptive responses to
      new challenges are mediated by germline epigenetic processes, which can be
      transmitted over variable number of generations, and argue that the heritable
      variations that are generated epigenetically have an impact on both small-scale
      and large-scale aspects of evolution. First, I review some recent ecological
      studies and models that show that germline (gametic) epigenetic inheritance can
      lead to cumulative micro-evolutionary changes that are rapid and semi
      directional. I suggest that "priming" and "epigenetic learning" may be of special
      importance in generating heritable, fine-tuned adaptive responses in populations.
      Second, I consider work showing how genomic and environmental stresses can also
      lead to epigenome repatterning, and produce changes that are saltational.

PMID- 22975444
TI  - Identification of novel and cross-species seroreactive proteins from Bacillus
      anthracis using a ligation-independent cloning-based, SOS-inducible expression
      system.
AB  - The current standard for Bacillus anthracis vaccination is the Anthrax Vaccine
      Adsorbed (AVA, BioThrax). While effective, the licensed vaccine schedule requires
      five intramuscular injections in the priming series and yearly boosters to
      sustain protection. One potential approach to maintain or improve the protection
      afforded by an anthrax vaccine, but requiring fewer doses, is through the use of
      purified proteins to enhance an antibody response, which could be used on their
      own or in combination with the current vaccine. This study describes a novel,
      high-throughput system to amplify and clone every gene in the B. anthracis pXO1
      and pXO2 virulence plasmids. We attempted to express each cloned gene in
      Escherichia coli, and obtained full-length expression of 57% of the proteins.
      Expressed proteins were then used to identify immunogens using serum from three
      different mammalian infection models: Dutch-belted rabbits, BALB/c mice, and
      rhesus macaque monkeys. Ten proteins were detected by antibodies in all of these
      models, eight of which have not been identified as immunoreactive in other
      studies to date. Serum was also collected from humans who had received the AVA
      vaccine, and similar screens showed that antigens that were detected in the
      infection models were not present in the serum of vaccinated humans, suggesting
      that antibodies elicited by the current AVA vaccine do not react with the
      immunoreactive proteins identified in this study. These results will contribute
      to the future selection of targets in antigenicity and protection studies as one
      or more of these proteins may prove to be worthy of inclusion in future vaccine
      preparations.

PMID- 22975445
TI  - Case report: Complex retroperitoneal herniation after abdominoperineal resection.
AB  - INTRODUCTION: We describe the occurrence of a retroperitoneal hernia into the
      colonic mesentery after abdomoniperineal resection (APR) for rectal cancer.
      PRESENTATION OF CASE: A 70year old male presented with complete small bowel
      obstruction secondary to a complex retroperitoneal herniation. Operative repair
      was carried out with successful reduction of the hernia contents. DISCUSSION: A
      review of the literature is reported concerning retroperitoneal hernia. This
      occurrence is rare in the adult. Management of the resultant pelvic space after
      APR is discussed. Closure of the pelvic peritoneum is helpful in avoiding this
      and other similar complications. CONCLUSION: We believe this to be the first
      report of a small bowel obstruction secondary to this unusual hernia
      circumstance. Although rare, due vigilance and thorough imaging can lead to
      effective and timely management of this complication.

PMID- 22975447
TI  - Role of microglia and toll-like receptor 4 in the pathophysiology of delirium.
AB  - Delirium is a serious medical condition that commonly afflicts elderly
      inpatients. This is especially common in the post-operative setting where it
      increases mortality, length of hospital stay and health care costs. The exact
      mechanisms involved in its pathogenesis remain uncertain and there is currently
      no effective pharmacological therapy for treatment or prevention of delirium. We
      hypothesize that microglia-mediated neuroinflammation via toll-like receptor 4
      signalling is a significant contributor to post-operative delirium. Based on our
      proposed mechanism, three novel pharmacological therapies have been suggested to
      be effective to prevent or treat delirium. Curcumin, ibudilast and minocycline
      have been shown to interfere with various steps in the proinflammatory microglial
      activation intracellular signalling pathway, disrupting the subsequent
      neuroinflammatory cascade. We hypothesize that these drugs could be a novel
      pharmacotherapy that could significantly improve the outcome of post-operative
      delirious patients.

PMID- 22975448
TI  - Does wet hair in cold weather cause sinus headache and posterior eye pain? A
      possible mechanism through selective brain cooling system.
AB  - As a general observation, wet hair in cold weather seems to be a predisposing
      factor for sinus headache and posterior eye pain. We offer a mechanism through
      selective brain cooling system for this observation. Selective brain cooling
      (SBC) is a mechanism to protect brain from hyperthermia. Components of SBC are
      head skin and upper respiratory tract (nose and paranasal sinuses). Cool venous
      blood from head skin and mucous membranes of nose and paranasal sinuses drains to
      intracranial dural sinuses and provide brain cooling. Brain will be cooled very
      much when head skin exposes to hypothermia such a condition like wet hair in cold
      weather. We suggest that, in order to reduce brain cooling activity, some
      alterations are being occurred within paranasal sinuses. For this purpose, sinus
      ostiums may close and mucus may accumulate to reduce air within sinuses. Also
      there may be some vasomotor changes to prevent heat loss. We hypothesize that
      this possible alterations may occur within paranasal sinuses as a control
      mechanism for brain temperature control during exposure of head skin to
      hypothermia. Paranasal sinuses may also cool brain directly by a very thin layer
      of bone separates the posterior ethmoid air sinus from the subarachnoid space and
      only thin plates of bone separate the sphenoidal sinuses from internal carotid
      artery and cavernous sinuses. Because of their critical role in the SBC,
      posterior ethmoid air sinus and sphenoidal sinuses may be affected from this
      alterations more than other paranasal sinuses. This situation may cause posterior
      eye pain. This mechanism can explain why a person who expose to hypothermia with
      wet hair or a person who don't use a beret or a hat during cold weather gets
      sinus headache and posterior eye pain. These symptoms could lead to an incorrect
      diagnosis of sinusitis.

PMID- 22975450
TI  - [Not Available].

PMID- 22975449
TI  - Histamine receptor 2-mediated growth-differentiation factor-15 expression is
      involved in histamine-induced melanogenesis.
AB  - Vitiligo is a progressive depigmenting disorder. Histamine has been shown to
      induce melanogenesis via histamine receptor 2, suggesting the possibility of
      histamine as a repigmenting agent for the treatment of vitiligo. However, the
      role and signaling mechanism of histamine are still unclear in melanogenesis,
      especially in relation to growth-differentiation factor-15, which is a protein
      belonging to transforming growth factor beta and found to be overexpressed in
      metastatic or malignant melanoma. We found that histamine induces growth
      differentiation factor-15 in melanoma cell lines such as SK-MEL-2, B16F10, and
      melan-a cells. Therefore, in the present study, the role of growth
      differentiation factor-15 in histamine-induced melanogenesis was investigated
      using gene silencing or overexpression of growth-differentiation factor-15 and
      histamine related compounds such as histamine, amthamine, and cimetidine. Gene
      silencing of growth-differentiation factor-15 suppressed histamine-induced
      proliferation, melanin production, tyrosinase activity, and chemotactic migration
      of SK-MEL-2 cells. Histamine-induced expression of tyrosinase, tyrosinase-related
      protein 1, and tyrosinase-related protein 2 was also suppressed by growth
      differentiation factor-15 gene silencing. On the other hand, overexpression of
      growth-differentiation factor-15 using a plasmid containing growth
      differentiation factor-15 in SK-MEL-2 cells increased melanin production and
      chemotactic migration. Amthamine induced expression of growth-differentiation
      factor-15 in a time and concentration dependent manner. Amthamine-induced
      expression of growth-differentiation factor-15 was suppressed by cimetidine. Our
      results suggest that growth-differentiation factor-15 is a new player in
      histamine-induced melanogenesis, which can help researchers to extend the
      knowledge of the role of the transforming growth factor beta family in
      melanogenesis and in skin pigment disorders such as vitiligo.

PMID- 22975451
TI  - Efficacy and safety of biphasic insulin aspart 30/70 in the treatment of patients
      with type 2 diabetes mellitus.
AB  - OBJECTIVE: To assess the safety and efficacy of biphasic insulin aspart 30/70 in
      patients with type 2 diabetes mellitus (DM2). MATERIAL AND METHODS: We performed
      an observational, multicenter, prospective study in 3,054 DM2 patients from
      primary care and specialized settings, treated with biphasic insulin aspart 30/70
      (started within 15 days prior to inclusion). In all patients,the following
      information was available before starting insulin treatment: HbA(1c) levels,
      fasting plasma glucose (FPG), 4-point glucose profile (before and 90 minutes
      after breakfast and dinner) and number of hypoglycemic episodes/week. A total of
      2,887 patients completed the study (26 +/- 1 week). The variables evaluated were
      rate of adverse events (AE), number of hypoglycemic episodes/week, HbA(1c), FPG
      and 4-point glucose profile. RESULTS: At least one AE occurred in 10.7% of the
      patients (2.3% related to the study drug and 1.4% severe). There was a
      significant decrease (end of study vs baseline; p < 0.0001 for all the
      comparisons) in HbA(1c) (7.3% and 8.9%, respectively), the mean number of minor
      (0.3/0.5) and major (0.02/0.07) hypoglycemic episodes/week, FPG (145/207 mg/dl)
      and postprandial glycemia (162/225 mg/dl). The improvement in metabolic control
      was achieved both in patients previously treated with oral antidiabetic drugs and
      in those treated with insulin. The number of hypoglycemic episodes decreased in
      patients previously treated with insulin. CONCLUSIONS: Treatment with biphasic
      insulin aspart 30/70 in patients with DM2 improves glycemic control, irrespective
      of previous treatment, with a low rate of AE and fewer hypoglycemic episodes in
      patients previously treated with insulin.

PMID- 22975452
TI  - Effectiveness of ezetimibe in routine clinical practice. Effect on lipid profile
      and other laboratory parameters.
AB  - INTRODUCTION AND OBJECTIVES: Dyslipidemia is frequently related to metabolic
      syndrome, which carries high cardiovascular risk. Statin therapy sometimes fails
      to achieve the recommended plasma lipid targets. The aim of this study was to
      evaluate the joint effect of ezetimibe and statin on lipid profile in
      dyslipidemic patients not achieving target values with statins alone and to
      determine the action of this combination on cardiovascular risk parameters, as
      well as its tolerability. METHODS: We performed a descriptive prospective study
      in 50 consecutive hypercholesterolemic patients treated with statin alone and
      with poor metabolic control. Lipid profile and plasma concentrations of insulin,
      ferritin and homocysteine were evaluated after 3 months of combined treatment
      with ezetimibe. RESULTS: We found a significant reductionin low density
      lipoproteins (p<0.001), a mean reduction in total cholesterol (p<0.001) and
      triglycerides (p=0.002), as well as decreases in plasma concentrations of
      ferritin (p=0,016), insulin (p=0,010) and homocysteine (p<0.001) of 5%, 5% and
      14%, respectively. There were no changes in either hepatic or muscular function.
      CONCLUSIONS: Combined treatment with ezetimibe and statin significantly improved
      lipid profile in poorly-controlled hypercholesterolemic patients treated with
      statin alone. There were no collateral effects on either hepatic or muscular
      parameters and there may be additional benefits on plasma levels of homocysteine,
      insulin and ferritin.

PMID- 22975446
TI  - Alcohol dependence as a chronic pain disorder.
AB  - Dysregulation of pain neurocircuitry and neurochemistry has been increasingly
      recognized as playing a critical role in a diverse spectrum of diseases including
      migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports
      the hypothesis that alcohol dependence is among the pathologies arising from
      aberrant neurobiological substrates of pain. In this review, we explore the
      possible influence of alcohol analgesia and hyperalgesia in promoting alcohol
      misuse and dependence. We examine evidence that neuroanatomical sites involved in
      the negative emotional states of alcohol dependence also play an important role
      in pain transmission and may be functionally altered under chronic pain
      conditions. We also consider possible genetic links between pain transmission and
      alcohol dependence. We propose an allostatic load model in which episodes of
      alcohol intoxication and withdrawal, traumatic stressors, and injury are each
      capable of dysregulating an overlapping set of neural substrates to engender
      sensory and affective pain states that are integral to alcohol dependence and
      comorbid conditions such as anxiety, depression, and chronic pain.

PMID- 22975453
TI  - Effects of traumatic brain injury and subarachnoid hemorrhage on anterior
      pituitary function.
AB  - Traumatic brain injuries and subarachnoid hemorrhage are frequent events in
      Spain. Both are well recognized causes of anterior hypopituitarism, the
      prevalence ranging from 20 to 80% according to recent series. Consensus is
      lacking on how to assess pituitary function after the injury, although periodic
      assessment is clearly needed because hypopituitarism may appear at any time in
      the first year after the event. Hormone replacement when necessary helps recovery
      and reduces morbidity and mortality.

PMID- 22975454
TI  - Contribution of positron emission tomography to the diagnosis of a case of
      acromegaly.
AB  - Diagnosis of acromegaly is based on biochemical tests demonstrating increased
      growth hormone (GH) secretion. More than 95% of patients with acromegaly harbor a
      GH-secreting pituitary adenoma. The technique of choice in the diagnosis of an
      adenoma is magnetic resonance imaging (MRI). The use of new techniques such as
      (111)In-octreotide scintigraphy (OctreoScan) and positron emission tomography
      (PET) can provide additional information in some cases. We report the case of a
      woman with acromegaly. The results of several MRI scans and OctreoScan were
      normal and other diagnostic possibilities were ruled out. The pituitary origin of
      the increased GH secretion was identified by PET. In acromegaly, the absence of
      MRI findings and identification of location by means of PET are exceptional.

PMID- 22975455
TI  - Citalopram- and escitalopram-induced symptomatic hyponatremia.
AB  - We report the cases of 2 patients who developed syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) after initiating therapy with the
      selective serotonin reuptake inhibitors, citalopram and escitalopram. Both the
      patients were women, aged 65 and 81 years old. The first consulted for headache,
      nausea and vomiting and the second for asthenia and malaise. Both were under
      treatment for depression with citalopram (20 mg/day) and escitalopram (10
      mg/day), respectively. We review the literature on SIADH induced by citalopram
      and escitalopram and the pathophysiological mechanisms of this syndrome.

PMID- 22975456
TI  - Primary epithelioid angiosarcoma of the thyroid: an infrequent malignant thyroid
      tumor.
AB  - We present a case of epithelioid angiosarcoma of the thyroid, a rare and
      aggressive tumor, in a 74-year-old woman with a chronic euthyroid goiter. The
      tumor, which involved most of the glandular surface of the thyroid, showed an
      infiltrating histological pattern, with epithelioid cells displaying a tendency
      to form vascular lights. Immunohistochemical analysis (CD31 and factor VIII)
      confirmed the angiomatous nature of the neoplasm and enabled us to establish the
      differential diagnosis with other malignant processes that can also affect this
      anatomical area.

PMID- 22975458
TI  - [Not Available].

PMID- 22975457
TI  - Multiple paraganglioma in a female patient: review of genetic features.
AB  - We report the case of a female patient who presented with symptoms of
      catecholamine excess. Urinary catecholamines were elevated. Radiologic tests were
      compatible with paraganglioma. High parathyroid hormone and gastrin values were
      also detected, which excluded multiple endocrine neoplasia type 1 and 2. Finally,
      the patient was diagnosed with multiple paraganglioma. This entity is associated
      with mutations in the SDHB-C-D genes. An SDHD mutation was found in our patient.
      The genetic bases, mutations, genotypephenotype associations, and tumorigenesis
      of SDH are currently being studied. The present article provides a review of the
      most recent data.

PMID- 22975459
TI  - [Not Available].

PMID- 22975460
TI  - Validity of ActiGraph 2-regression model, Matthews cut-points, and NHANES cut
      points for assessing free-living physical activity.
AB  - BACKGROUND: The purpose of this study was to compare the 2006 and 2010 Crouter
      algorithms for the ActiGraph accelerometer and the NHANES and Matthews cut
      points, to indirect calorimetry during a 6-hr free-living measurement period.
      METHODS: Twenty-nine participants (mean +/- SD; age, 38 +/- 11.7 yrs; BMI, 25.0
      +/- 4.6 kg.m-2) were monitored for 6 hours while at work or during their leisure
      time. Physical activity (PA) data were collected using an ActiGraph GT1M and
      energy expenditure (METs) was measured using a Cosmed K4b2. ActiGraph prediction
      equations were compared with the Cosmed for METs and time spent in sedentary
      behaviors, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA). RESULTS: The
      2010 Crouter algorithm overestimated time spent in LPA, MPA, and VPA by 9.0%
      44.5% and underestimated sedentary time by 20.8%. The NHANES cut-points
      overestimated sedentary time and LPA by 8.3%-9.9% and underestimated MPA and VPA
      by 50.4%-56.7%. The Matthews cut-points overestimated sedentary time (9.9%) and
      MPA (33.4%) and underestimated LPA (25.7%) and VPA (50.1%). The 2006 Crouter
      algorithm was within 1.8% of measured sedentary time; however, mean errors ranged
      from 34.4%-163.1% for LPA, MPA, and VPA. CONCLUSION: Of the ActiGraph prediction
      methods examined, none of them was clearly superior for estimating free-living PA
      compared with indirect calorimetry.

PMID- 22975461
TI  - Strategies of locomotor collision avoidance.
AB  - Collision avoidance during locomotion can be achieved by a variety of strategies.
      While in some situations only a single trajectory will successfully avoid impact,
      in many cases several different strategies are possible. Locomotor experiments in
      the presence of static boundary conditions have suggested that the choice of an
      appropriate trajectory is based on a maximum-smoothness strategy. Here we
      analyzed locomotor trajectories of subjects avoiding collision with another human
      crossing their path orthogonally. In such a case, changing walking direction
      while keeping speed or keeping walking direction while changing speed would be
      two extremes of solving the problem. Our participants clearly favored changing
      their walking speed while keeping the path on a straight line between start and
      goal. To interpret this result, we calculated the costs of the chosen
      trajectories in terms of a smoothness-maximization criterion and simulated the
      trajectories with a computational model. Data analysis together with model
      simulation showed that the experimentally chosen trajectory to avoid collision
      with a moving human is not the optimally smooth solution. However, even though
      the trajectory is not globally smooth, it was still locally smooth. Modeling
      further confirmed that, in presence of the moving human, there is always a
      trajectory that would be smoother but would deviate from the straight line. We
      therefore conclude that the maximum smoothness strategy previously suggested for
      static environments no longer holds for locomotor path planning and execution in
      dynamically changing environments such as the one tested here.

PMID- 22975462
TI  - Effects of calcitonin gene-related peptide on the immune privilege of human hair
      follicles.
AB  - The hair follicle is a widely available and instructive miniature organ in the
      human body that experiences major histocompatibility complex (MHC) class I
      dependent immune privilege (IP). There are various regulation factors that act on
      the generation, maintenance, and collapse of hair follicle IP. Neuropeptides such
      as calcitonin gene-related peptide (CGRP) are created in many organs, including
      skin, and display various immune regulation effects. The purpose of this study
      was to investigate the phenotypic effect of CGRP on the hair follicle's IP.
      First, we used interferon-gamma (IFN-gamma) to generate ectopic MHC antigen
      expression model in cultured human hair follicles as previously described. Then,
      we examined the effects of CGRP on the regulation of ectopic MHC antigen
      expression in cultured human hair follicles using reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemical staining techniques.
      IFN-gamma (75 IU/ml) induced ectopic MHC expression. CGRP down-regulated INF
      gamma-induced ectopic MHC class I mRNA expression. These down-regulated effects
      were especially evident in 10(-8)M. In addition, CGRP also suppressed the
      staining intensity related to the expression of MHC class I and MHC class I
      pathway related molecules (beta2-microglobulin), but had no effect on MHC class
      II antigen expression. Taken together, these results indicate that CGRP might be
      an important regulatory factor for IP maintenance and restoration of IP via
      suppression of MHC class I antigen.

PMID- 22975463
TI  - Facet joint contact pressure is not significantly affected by ProDisc cervical
      disc arthroplasty in sagittal bending: a single-level cadaveric study.
AB  - BACKGROUND CONTEXT: Total disc arthroplasty is a motion-preserving spinal
      procedure that has been investigated for its impact on spinal motions and
      adjacent-level degeneration. However, the effects of disc arthroplasty on facet
      joint biomechanics remain undefined despite the critical role of these posterior
      elements on guiding and limiting spinal motion. PURPOSE: The goal was to measure
      the pressure in the facet joint in cadaveric human cervical spines subjected to
      sagittal bending before and after implantation of the ProDisc-C (Synthes Spine
      Company, L.P, West Chester, PA, USA). STUDY DESIGN: A biomechanical study was
      performed using cadaveric human cervical spines during sagittal bending in the
      intact and implanted conditions. METHODS: Seven C2-T1 osteoligamentous cadaveric
      cervical spines were instrumented with a transducer to measure the C5-C6 facet
      pressure profiles during physiological sagittal bending, before and after
      implantation of a ProDisc-C at that level. Rotations of the index segment and
      global cervical spine were also quantified. RESULTS: The mean C5-C6 range of
      motion significantly increased (p=.009) from 9.6 degrees +/-5.1 degrees  in the
      intact condition to 16.2 degrees +/-3.6 degrees  after implantation. However,
      despite such changes in rotation, there was no significant difference in the
      facet contact pressure during extension between the intact (64+/-30 kPa) and
      implanted (44+/-55 kPa) conditions. Similarly, there was no difference in facet
      pressure developed during flexion. CONCLUSIONS: Although implantation of a
      ProDisc-C arthroplasty device at the C5-C6 level increases angular rotations, it
      does not significantly alter the local facet pressure at the index level in
      flexion or extension. Using a technique that preserves the capsular ligament,
      this study provides the first direct measurement of cervical facet pressure in a
      disc arthroplasty condition.

PMID- 22975464
TI  - [Characteristics of nursing publications in journals with impact factor].
AB  - The aims of this study were to identify publishing characteristics of nursing
      journals with impact factor (IF) and to discuss methodological characteristics
      and authorship of original papers with IF. METHODS: A retrospective descriptive
      study. A literature review was performed between 2009 and 2010 including all
      nursing publications indexed in the Journal Citation Reports (JCR) and analysis
      of selected original papers. The information was analyzed using descriptive
      statistics. RESULTS: In 2009, there were 74 nursing journals with an IF and in
      2010 increased upto 91. In 2010, 93.5% were published in English, bimonthly
      journals predominated (43%) and for specialties, maternity and paediatrics were
      the most frequent (25%). Almost three-quarters (72.8%) of the original articles
      were quantitative studies performed mostly in hospitals (42%) and with patient
      samples (34.6%). The most frequently studied topics were "evidence-based care"
      (23.5%), "measuring quality care" (18.52%) and "effectiveness of nursing
      interventions" (14.81%). Authors came mostly from Europe and United States and
      the most common workplace was a university. CONCLUSIONS: Nursing Journals' Impact
      Factor has increased, particularly in areas of nurse specialization. Nursing
      publications in the Spanish language with IF are still incipient. Quantitative
      research continues to dominate. The main topics are effectiveness, evidence, and
      quality care, and researchers come mostly from academic areas.

PMID- 22975466
TI  - Relation of uric acid to serum levels of high-sensitivity C-reactive protein,
      triglycerides, and high-density lipoprotein cholesterol and to hepatic steatosis.
AB  - Increased uric acid (UA) is strongly linked to cardiovascular disease. However,
      the independent role of UA is still debated because it is associated with several
      cardiovascular risk factors including obesity and metabolic syndrome. This study
      assessed the association of UA with increased high-sensitivity C-reactive protein
      (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol
      (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the
      presence and absence of obesity and metabolic syndrome. We evaluated 3,518
      employed subjects without clinical cardiovascular disease from November 2008
      through July 2010. Prevalence of hs-CRP >=3 mg/L was 19%, that of TG/HDL >=3 was
      44%, and that of hepatic steatosis was 43%. In multivariable logistic regression
      after adjusting for traditional cardiovascular risk factors and confounders,
      highest versus lowest UA quartile was associated with hs-CRP >=3 mg/L (odds ratio
      [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL >=3 (OR
      3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22
      to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association
      of UA with hs-CRP >=3 mg/L became nonsignificant in analyses stratified by
      obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a
      graded increase in the odds of having 2 or 3 of these risk conditions and a
      successive decrease in the odds of having none. In conclusion, high UA levels
      were associated with increased TG/HDL and hepatic steatosis independently of
      metabolic syndrome and obesity and with increased hs-CRP independently of
      metabolic syndrome.

PMID- 22975465
TI  - Meta-analysis of perceived stress and its association with incident coronary
      heart disease.
AB  - Most studies examining potential associations between psychological factors and
      cardiovascular outcomes have focused on depression or anxiety. The effect of
      perceived stress on incident coronary heart disease (CHD) has yet to be reviewed
      systematically. We conducted a systematic review and meta-analysis of the
      association between perceived stress and incident CHD. Ovid, MEDLINE, and
      PsycINFO were searched as data sources. Prospective observational cohort studies
      were selected that measured self-reported perceived stress and assessed incident
      CHD at >=6 months. We extracted study characteristics and estimates of the risk
      of incident CHD associated with high perceived stress versus low perceived
      stress. We identified 23 potentially relevant articles, of which 6 met our
      criteria (n = 118,696). Included studies measured perceived stress with validated
      measurements and nonvalidated simple self-report surveys. Incident CHD was
      defined as new diagnosis of, hospitalization for, or mortality secondary to CHD.
      Meta-analysis yielded an aggregate risk ratio of 1.27 (95% confidence interval
      1.12 to 1.45) for the magnitude of the relation between high perceived stress and
      incident CHD. In conclusion, this meta-analysis suggests that high perceived
      stress is associated with a moderately increased risk of incident CHD.

PMID- 22975467
TI  - Urine calcium excretion, cardiovascular events, and mortality in outpatients with
      stable coronary artery disease (from the Heart and Soul study).
AB  - We sought to evaluate the association of urine calcium excretion (UCaE), which
      reflects systemic calcium absorption, with cardiovascular (CV) events and
      mortality in outpatients with prevalent coronary heart disease (CHD). Calcium
      supplementation is associated with vascular calcification and adverse CV outcomes
      in patients with end-stage renal disease. Recent studies have raised concern that
      this phenomenon may also extend to the general population. However, previous
      studies have assessed oral calcium intake, which correlates poorly with systemic
      calcium absorption. We measured UCaE from 24-hour urine collections provided by
      903 outpatients who were recruited from 2000 to 2002. We used Cox proportional
      hazard models to evaluate the association of baseline UCaE with a primary end
      point of any CV event (myocardial infarction [MI], heart failure, stroke, or CV
      mortality). During a mean follow-up of 6 +/- 3 years, 287 subjects (32%) had a CV
      event. After multivariate adjustment for demographics, traditional CV risk
      factors, and kidney function, there was no association between UCaE and the
      primary end point of any CV event (per 10-mg/day greater UCaE, hazard ratio 1.00,
      95% confidence interval 0.98 to 1.02). Evaluation of individual CV outcomes
      revealed a lower rate of MI with higher UCaE (hazard ratio 0.97, 95% confidence
      interval 0.94 to 1.00). In conclusion, greater UCaE is not associated with higher
      overall CV event rates or mortality in outpatients with stable CHD. On the
      contrary, greater UCaE is associated with a modestly lower rate of MI. These
      findings suggest that greater systemic calcium absorption does not confer CV harm
      in outpatients with prevalent CHD.

PMID- 22975468
TI  - Impact of emergency coronary angiography on in-hospital outcome of unconscious
      survivors after out-of-hospital cardiac arrest.
AB  - Acute coronary thrombotic occlusion is the most common trigger of cardiac arrest.
      The aim of the present study was to assess the impact of an invasive strategy
      characterized by emergency coronary angiography and subsequent percutaneous
      coronary intervention (PCI), if indicated, on in-hospital survival of
      resuscitated patients with out-of-hospital cardiac arrest (OHCA) and no obvious
      extracardiac cause who do not regain consciousness soon after recovery of
      spontaneous circulation. Ninety-three consecutive patients (67 +/- 12 years old,
      76% men) were included in the study. Clinical characteristics and coronary
      angiographic and in-hospital outcome data were retrospectively collected.
      Multivariate Cox proportional-hazards analysis was performed to identify
      independent determinants of in-hospital survival. Coronary angiography was
      performed in 66 patients (71%). Forty-eight patients underwent emergency coronary
      angiography; in the remaining 18 patients, mean time from OHCA to coronary
      angiography was 13 +/- 10 days. In patients referred to emergency coronary
      angiography, successful emergency PCI of a culprit coronary lesion was performed
      in 25 patients (52%). In-hospital survival rate was 54%. At multivariate
      analysis, emergency coronary angiography (hazard ratio 2.32, 95% confidence
      interval 1.23 to 4.38, p = 0.009) and successful emergency PCI (hazard ratio
      2.54, 95% confidence interval 1.35 to 4.8, p = 0.004) were independently related
      to in-hospital survival in the overall study population; delay in performing
      coronary angiography (hazard ratio 0.95, 95% confidence interval 0.92 to 0.99, p
      = 0.013) was independently related to in-hospital mortality in patients referred
      to coronary angiography. In conclusion, an invasive strategy characterized by
      emergency coronary angiography and subsequent PCI, if indicated, seems to improve
      in-hospital outcome of resuscitated but unconscious patients with OHCA without
      obvious extracardiac cause.

PMID- 22975470
TI  - Price elasticity of expenditure across health care services.
AB  - Policymakers in countries around the world are faced with rising health care
      costs and are debating ways to reform health care to reduce expenditures.
      Estimates of price elasticity of expenditure are a key component for predicting
      expenditures under alternative policies. Using unique individual-level data
      compiled from administrative records from the Chilean private health insurance
      market, I estimate the price elasticity of expenditures across a variety of
      health care services. I find elasticities that range between zero for the most
      acute service (appendectomy) and -2.08 for the most elective (psychologist
      visit). Moreover, the results show that at least one third of the elasticity is
      explained by the number of visits; the rest is explained by the intensity of each
      visit. Finally, I find that high-income individuals are five times more price
      sensitive than low-income individuals and that older individuals are less price
      sensitive than young individuals.

PMID- 22975469
TI  - Development of a standardized approach for environmental microbiota
      investigations related to asthma development in children.
AB  - Standardized studies examining environmental microbial exposure in populations at
      risk for asthma are necessary to improve our understanding of the role this
      factor plays in disease development. Here we describe studies aimed at developing
      guidelines for high-resolution culture-independent microbiome profiling, using a
      phylogenetic microarray (PhyloChip), of house dust samples in a cohort collected
      as part of the NIH-funded Inner City Asthma Consortium (ICAC). We demonstrate
      that though extracted DNA concentrations varied across dust samples, the majority
      produced sufficient 16S rRNA to be profiled by the array. Comparison of array and
      454-pyrosequencing performed in parallel on a subset of samples, illustrated that
      increasingly deeper sequencing efforts validated greater numbers of array
      detected taxa. Community composition agreement across samples exhibited a
      hierarchy in concordance, with the highest level of agreement in replicate array
      profiles followed by samples collected from adjacent 1*1 m(2) sites in the same
      room, adjacent sites with different sized sampling quadrants (1*1 and 2*2 m(2)),
      different sites within homes (living and bedroom) to lowest in living room
      samples collected from different homes. The guidelines for sample collection and
      processing in this pilot study extend beyond PhyloChip based studies of house
      associated microbiota, and bear relevance for other microbiome profiling
      approaches such as next-generation sequencing.

PMID- 22975471
TI  - On insuring and caring for parents' long-term care needs.
AB  - When adult children are financially responsible for their parents, they can take
      considerable interest in the amount of their parents' long-term care (LTC)
      insurance. In this paper, we look at the optimal levels of LTC insurance and of
      informal care, and at the link between these two decisions when the child, who
      provides informal care, is also the decision-maker with regard to LTC insurance.
      Interestingly, results differ depending on the degree of both parental and child
      altruism and indicate either complementarity or substitutability between
      insurance and informal care. In particular, we show in the presence of child
      altruism that insurance stimulates the offer of informal care, contrary to the
      case where the insurance decision is made by the elderly parent. We also
      investigate how exogenous shocks with respect to the opportunity cost of informal
      care, initial wealth levels and bequests modify simultaneously the optimal level
      of insurance and informal care.

PMID- 22975472
TI  - Surface roughness enhances the osseointegration of titanium headposts in non
      human primates.
AB  - It is well recognized that micrometer and nanometer sized surface features
      enhance the skeletal attachment of implants within bone. However, little is known
      regarding the integration of implants placed outside the bone but in contact with
      the surface. Loosening of chronic skull anchored headposts in non-human primate
      based experiments can be a factor. The purpose of this study was to evaluate the
      effect of a simple and easily applied surface texture on bone apposition to
      titanium implants fixed to the periosteal surface of the skull. Implants
      possessed either a polished surface or a textured surface created by grit-basting
      followed by acid etching. The percent of bone in contact with the implant surface
      (bone apposition) to three polished and three textured implants was evaluated in
      one adult female monkey after 14 weeks. Upon harvest, implants were processed for
      undecalcified histology and regions of bone apposition were quantified using
      backscatter electron microscopy and digital image analysis. The bone apposition
      to textured implants was 62+/-20% and to polished implants was 42+/-21%. The
      application of a peak-and-pit like texture to the surface of titanium implants
      significantly increased bone apposition to titanium implants placed on the
      periosteal surface of the skull. This study demonstrates that titanium headposts
      can easily be modified to improve osseointegration using equipment and supplies
      available to most neurophysiological laboratories. In addition, implant texturing
      may have utility in areas including skeletal trauma and reconstruction where
      devices are placed in contact with the bone surface.

PMID- 22975474
TI  - An organotypic spinal cord slice culture model to quantify neurodegeneration.
AB  - Activated microglia cells have been implicated in the neurodegenerative process
      of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic
      lateral sclerosis, and multiple sclerosis; however, the precise roles of
      microglia in disease progression are unclear. Despite these diseases having been
      described for more than a century, current FDA approved therapeutics are
      symptomatic in nature with little evidence to supporting a neuroprotective
      effect. Furthermore, identifying novel therapeutics remains challenging due to
      undetermined etiology, a variable disease course, and the paucity of validated
      targets. Here, we describe the use of a novel ex vivo spinal cord culture system
      that offers the ability to screen potential neuroprotective agents, while
      maintaining the complexity of the in vivo environment. To this end, we treated
      spinal cord slice cultures with lipopolysaccharide and quantified neuron
      viability in culture using measurements of axon length and FluoroJadeC intensity.
      To simulate a microglia-mediated response to cellular debris, antigens, or
      implanted materials/devices, we supplemented the culture media with increasing
      densities of microspheres, facilitating microglia-mediated phagocytosis of the
      particles, which demonstrated a direct correlation between the phagocytic
      activities of microglia and neuronal health. To validate our model's capacity to
      accurately depict neuroprotection, cultures were treated with resveratrol, which
      demonstrated enhanced neuronal health. Our results successfully demonstrate the
      use of this model to reproducibly quantify the extent of neurodegeneration
      through the measurement of axon length and FluoroJadeC intensity, and we suggest
      this model will allow for accurate, high-throughput screening, which could result
      in expedited success in translational efficacy of therapeutic agents to clinical
      trials.

PMID- 22975475
TI  - Biological control of trichostrongyles in beef cattle by the nematophagous fungus
      Duddingtonia flagrans in tropical southeastern Brazil.
AB  - The efficacy of a fungal formulation based on the nematophagous fungus
      Duddingtonia flagrans was assessed in the control of cattle trichostrongyles.
      Twenty male Nellore calves, six-month-old, divided in two groups (fungus-treated
      and control without fungus) were fed on a pasture of Brachiaria decumbens
      naturally infected with larvae of bovine trichostrongyles. Animals of the treated
      group received doses of sodium alginate mycelial pellets orally (1 g/10 kg live
      weight, twice a week), for 12 months. Feces samples were collected for egg count
      (eggs per gram of feces-EPG) and coprocultures during 12 months. There was a
      significant reduction in EPG (56.7%) and infective larvae (L3) in coprocultures
      (60.5%) for animals of the treated group in relation to the control group at the
      end of the study. There was a significant reduction of L3 (64.5%) in herbage
      samples collected up to 0-20 cm from fecal pats and 73.2% in distant samples (20
      40 cm) between the fungus-treated group and the control group. The treatment with
      sodium alginate pellets containing the nematode trapping fungus D. flagrans
      reduced trichostrongylid in tropical southeastern Brazil and could be an
      effective tool for biological control of this parasitic nematode in beef cattle.

PMID- 22975473
TI  - Positive impact of pre-stroke surgery on survival following transient focal
      ischemia in hypertensive rats.
AB  - We describe a positive influence of pre-stroke surgery on recovery and survival
      in a commonly used experimental stroke model. Two groups of male, stroke-prone
      spontaneously hypertensive rats (SHRSPs) underwent transient middle cerebral
      artery occlusion (tMCAO). Group 1 underwent the procedure without any prior
      intervention whilst group 2 had an additional general anaesthetic 6 days prior to
      tMCAO for a cranial burrhole and durotomy. Post-stroke recovery was assessed
      using a 32 point neurological deficit score and tapered beam walk and infarct
      volume determined from haematoxylin-eosin stained sections. In group 2 survival
      was 92% (n=12) versus 67% in group 1 (n=18). In addition, post-tMCAO associated
      weight loss was significantly reduced in group 2. There was no significant
      difference between the two groups in experimental outcomes: infarct volume (Group
      1 317+/-18.6 mm3 versus Group 2 332+/-20.4 mm3), and serial (day 0-14 post-tMCAO)
      neurological deficit scores and tapered-beam walk test. Drilling a cranial
      burrhole under general anaesthesia prior to tMCAO in SHRSP reduced mortality and
      gave rise to infarct volumes and neurological deficits similar to those recorded
      in surviving Group 1 animals. This methodological refinement has significant
      implications for animal welfare and group sizes required for intervention
      studies.

PMID- 22975476
TI  - Evaluation of circulating concentrations of CXCL1 (Gro-alpha), CXCL10 (IP-10) and
      CXCL12 (SDF-1) in ALL patients prior and post bone marrow transplantation.
AB  - The immune system plays an important role in the development of leukemia. CXC
      chemokines, as the molecular members of this system, are involved in the immune
      responses. Therefore, this study was designed to examine and compare the levels
      of CXCL1 (Gro-alpha), CXCL10 (IP-10) and CXCL12 (SDF-1) in ALL patients prior to
      and post bone marrow transplantation (BMT). In this experimental study, samples
      were obtained from ALL patients and controls, and subjected to ELISA for
      detection of chemokines. Demographic data were also collected by a questionnaire.
      Data were analyzed using SPSS software. Our results showed that the serum levels
      of CXCL1 (Gro-alpha), CXCL10 (IP-10) and CXCL12 (SDF-1) were significantly
      increased in ALL patients compared to the controls. We also showed that the
      CXCL10 (IP-10) level was increased after BMT in ALL patients, while CXCL1 (Gro
      alpha) and CXCL12 (SDF-1) were inversely decreased. Our results allow for the
      conclusion that CXCL1 (Gro-alpha), CXCL10 (IP-10) and CXCL12 (SDF-1) are
      important for the pathogenesis of ALL. Notably, these chemokines might be used as
      pivotal biological markers in the diagnosis of leukemia. Recombinant CXCL1 (Gro
      alpha), CXCL10 (IP-10) and CXCL12 (SDF-1) may be applied as a therapeutic
      approach in the treatment of leukemia patients.

PMID- 22975478
TI  - The effects of particulate ambient air pollution on the murine umbilical cord and
      its vessels: a quantitative morphological and immunohistochemical study.
AB  - Previous studies have shown that particulate matter (PM) compromise birth weight
      and placental morphology. We hypothesized that exposing mice to ambient PM would
      affect umbilical cord (UC) morphology. To test this, mice were kept in paired
      open-top exposure chambers at the same location and ambient conditions but, in
      one chamber, the air was filtered (F) and, in the other, it was not (NF). UCs
      were analysed stereologically and by immunohistochemistry to localize isoprostane
      and endothelin receptors. The cords of mice from NF chambers were smaller in
      volume due to loss of mucoid connective tissue and decrease in volume of
      collagen. These structural changes and in umbilical vessels were associated with
      greater volumes of regions immunostained for isoprostane, ET(A)R and ET(B)R.
      Findings indicate that the adverse effects of PM on birth weight may be mediated
      in part by alterations in UC structure or imbalances in the endogenous regulators
      of vascular tone and oxidative stress.

PMID- 22975479
TI  - [Evolution of non-typhoidal salmonellosis in the north of the province of
      Pontevedra, Spain (2003-2010)].

PMID- 22975477
TI  - Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic
      transgenerational inheritance of disease and sperm epimutations.
AB  - Environmental compounds are known to promote epigenetic transgenerational
      inheritance of disease. The current study was designed to determine if a
      "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta
      toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and
      associated DNA methylation epimutations in sperm. Gestating F0 generation female
      rats were exposed during fetal gonadal sex determination and the incidence of
      disease evaluated in F1 and F3 generations. There were significant increases in
      the incidence of total diseases in animals from pesticide lineage F1 and F3
      generation animals. Pubertal abnormalities, testis disease, and ovarian disease
      (primordial follicle loss and polycystic ovarian disease) were increased in F3
      generation animals. Analysis of the pesticide lineage F3 generation sperm
      epigenome identified 363 differential DNA methylation regions (DMR) termed
      epimutations. Observations demonstrate that a pesticide mixture (permethrin and
      DEET) can promote epigenetic transgenerational inheritance of adult onset disease
      and potential sperm epigenetic biomarkers for ancestral environmental exposures.

PMID- 22975480
TI  - [Adverse consequences for the human immunodeficiency virus epidemic in Spain
      following the new legal health framework on the illegal immigrants - save today
      and pay more tomorrow].

PMID- 22975481
TI  - Development and evaluation of social cognitive measures related to adolescent
      physical activity.
AB  - BACKGROUND: This study aimed to develop and evaluate the construct validity and
      reliability of modernized social cognitive measures relating to physical activity
      behaviors in adolescents. METHODS: An instrument was developed based on
      constructs from Bandura's Social Cognitive Theory and included the following
      scales: self-efficacy, situation (perceived physical environment), social
      support, behavioral strategies, and outcome expectations and expectancies. The
      questionnaire was administered in a sample of 171 adolescents (age = 13.6 +/- 1.2
      years, females = 61%). Confirmatory factor analysis was employed to examine model
      fit for each scale using multiple indices, including chi-square index,
      comparative-fit index (CFI), goodness-of-fit index (GFI), and the root mean
      square error of approximation (RMSEA). Reliability properties were also examined
      (ICC and Cronbach's alpha). RESULTS: Each scale represented a statistically sound
      measure: fit indices indicated each model to be an adequate-to-exact fit to the
      data; internal consistency was acceptable to good (alpha = 0.63-0.79); rank order
      repeatability was strong (ICC = 0.82-0.91). CONCLUSIONS: Results support the
      validity and reliability of social cognitive scales relating to physical activity
      among adolescents. As such, the developed scales have utility for the
      identification of potential social cognitive correlates of youth physical
      activity, mediators of physical activity behavior changes and the testing of
      theoretical models based on Social Cognitive Theory.

PMID- 22975482
TI  - The dorsal motor nucleus of the vagus (DMNV) in sudden infant death syndrome
      (SIDS): pathways leading to apoptosis.
AB  - Sudden infant death syndrome (SIDS) remains the commonest cause of death in the
      post-neonatal period in the developed world. A leading hypothesis is that an
      abnormality in the brainstem of infants who succumb to SIDS, either causes or
      predisposes to failure to respond appropriately to an exogenous stressor.
      Neuronal apoptosis can lead to loss of cardiorespiratory reflexes, compromise of
      the infant's ability to respond to stressors such as hypoxia, and ultimately a
      sleep-related death. The dorsal motor nucleus of the vagus (DMNV) is a medullary
      autonomic nucleus where abnormalities have regularly been identified in SIDS
      research. This review collates neurochemical findings documented over the last 30
      years, including data from our laboratory focusing on neuronal apoptosis and the
      DMNV, and provides potential therapeutic interventions targeting
      neurotransmitters, growth factors and/or genes.

PMID- 22975483
TI  - Influence of the number of elongated fiducial markers on the localization
      accuracy of the prostate.
AB  - Implanting fiducial markers for localization purposes has become an accepted
      practice in radiotherapy for prostate cancer. While many correction strategies
      correct for translations only, advanced correction protocols also require
      knowledge of the rotation of the prostate. For this purpose, typically, three or
      more markers are implanted. Elongated fiducial markers provide more information
      about their orientation than traditional round or cylindrical markers.
      Potentially, fewer markers are required. In this study, we evaluate the effect of
      the number of elongated markers on the localization accuracy of the prostate. To
      quantify the localization error, we developed a model that estimates, at
      arbitrary locations in the prostate, the registration error caused by
      translational and rotational uncertainties of the marker registration. Every
      combination of one, two and three markers was analysed for a group of 24
      patients. The average registration errors at the prostate surface were 0.3-0.8 mm
      and 0.4-1 mm for registrations on, respectively, three markers and two markers
      located on different sides of the prostate. Substantial registration errors (2.0
      2.2 mm) occurred at the prostate surface contralateral to the markers when two
      markers were implanted on the same side of the prostate or only one marker was
      used. In conclusion, there is no benefit in using three elongated markers: two
      markers accurately localize the prostate if they are implanted at some distance
      from each other.

PMID- 22975484
TI  - Circadian clock-deficient mice as a tool for exploring disease etiology.
AB  - One of the most significant conceptual changes brought about by the analysis of
      circadian clock-deficient mice is that abnormalities in the circadian clock are
      linked not only to sleep arousal disorder but also to a wide variety of common
      diseases, including hypertension, diabetes, obesity, and cancer. It has recently
      been shown that the disruption of the two cryptochrome genes Cry1 and Cry2-core
      elements of the circadian clock-induces salt-dependent hypertension due to
      abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal
      gland. This adrenal disorder occurs as a result of increased expression of
      Hsd3b6, a newly identified steroidogenic enzyme that regulates aldosterone
      production within the adrenal zona glomerular cells. Importantly, this enzyme is
      functionally conserved in humans, and the pathophysiologic condition of human
      idiopathic hyperaldosteronism resembles that of Cry1/2-deficient mice. This
      review highlights the potential utility of circadian clock-deficient mice as a
      tool for exploring hitherto unknown disease etiology linked to the circadian
      clock.

PMID- 22975485
TI  - Challenge of mass spectrometry toward the elucidation of life phenomena.
      Foreword.

PMID- 22975486
TI  - FD-LC-MS/MS method for determining protein expression and elucidating biochemical
      events in tissues and cells.
AB  - To study biochemical events in tissues and cells, we have developed a novel
      proteomics approach, FD-LC-MS/MS, which consists of fluorogenic derivatization
      (FD), LC separation and detection/quantification of proteins in a biological
      sample, followed by the isolation and tryptic digestion of target proteins, and
      then their identification using nano-HPLC-MS/MS. Fluorogenic reagents such as 7
      chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulphonamide (DAABD-Cl)
      were designed to have high sensitivity for HPLC-fluorescence and -MS/MS detection
      and reactivity for cysteine residues in proteins. This comprehensive differential
      proteomics approach was applied to several tissues, such as mouse liver, mouse
      brain, horse muscle, breast cancer cell lines, and mouse heart, in order to study
      fluctuations in protein levels in tissues and cells.

PMID- 22975487
TI  - Salivary hormone measurement using LC/MS/MS: specific and patient-friendly tool
      for assessment of endocrine function.
AB  - Saliva has recently been attracting attention as a patient-friendly available bio
      fluid and an alternative to serum/plasma for hormone tests. LC coupled with
      atmospheric pressure ionization-MS/MS, especially electrospray ionization (ESI)
      MS/MS, has been recently valued as a highly specific method in the analysis of
      salivary hormones. In this article, LC/ESI-MS/MS assays for salivary hormones are
      overviewed according to the papers that have been published during the last 5
      years. Practical derivatization to enhance the detectabilities of hormones in ESI
      MS/MS is also discussed, because a major disadvantage of using saliva is low
      hormone concentrations.

PMID- 22975488
TI  - Proteomic approaches to profiling the humoral immune response and identifying
      disease-associated antigens.
AB  - In many diseases (e.g. autoimmune diseases, cancer), a humoral immune response is
      thought to be involved; therefore, identifying relevant antigens that trigger the
      humoral immune response is at the heart of current approaches for discovering
      biomarkers and designing therapeutic strategies. Although immunoblotting and
      protein array have been used for antigen profiling in several diseases, with the
      rapid progress in mass spectrometry (MS) and separation technologies, MS-based
      proteomic methods have become a promising tool for identifying disease-associated
      antigens. This review introduces MS-based antigen profiling methods
      (immunoproteomics and immune complexome analysis) and presents application
      examples of these techniques to the analysis of biological samples.

PMID- 22975489
TI  - Quantitative approach for small molecules using laser desorption/ionization mass
      spectrometry.
AB  - Recent advances in quantitative approaches to laser desorption/ionization mass
      spectrometry (LDI-MS) are selectively reviewed. Numerous efforts have been made
      to use matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)
      and related techniques for rapid screening and/or monitoring of biological
      events. Among the various mass ionization spectrometric analysis techniques,
      MALDI-MS has exceptional potential for high-throughput analysis. Although
      quantitative analysis with MALDI-MS is challenging, the expansion of its utility
      is inevitable. It is notable that practical improvement of MALDI-MS can be
      achieved by preparation of an uniform matrix using binary matrix systems. Broad
      applications have been established with a self-assembled monolayer for MALDI-MS,
      referred to as SAMDI-MS. The method could be an essential tool not only for rapid
      screening but also as a sensitive probe for surface sciences. Complementary to
      these approaches, labeling of molecules for LDI-MS is introduced as potential
      tool for the selective detection of specific target molecules.

PMID- 22975491
TI  - Molecular and functional analysis of cellular phenomena using single-cell mass
      spectrometry.
AB  - Single-cell analysis has attracted attention in many fields of biological studies
      as a tool to survey the precise mechanisms of cellular and molecular behavior.
      The development of sensitive mass spectrometry allows the study of molecules in
      single cells or small regions. Matrix-assisted laser desorption/ionization
      imaging mass spectrometry and secondary-ion mass spectrometry use in situ
      ionization of specimens on sample plates to visualize molecular distributions as
      images from mass spectra. Several single-cell mass spectrometry technologies that
      initially recover a single cell followed by ionization have been developed. Among
      them, only nanospray-mediated sampling and ionization named Live Single-cell Mass
      Spectrometry can be used for real-time analysis. This paper explains that method
      in detail.

PMID- 22975490
TI  - Development of imaging mass spectrometry.
AB  - We have developed a mass microscope in which a microscope is combined with high
      resolution matrix assisted laser desorption/ionization-imaging mass spectrometry
      (MALDI-IMS). This technique is a powerful tool for investigating the spatial
      distribution of biomolecules without the need for any time-consuming extraction,
      purification, and labeling procedures for biological tissue sections. The mass
      microscope provides clear images with regards to the distribution of hundreds of
      biomolecules in a single measurement, and also helps in determining the cellular
      profile of the biological system. In this review, we focus on some of the recent
      developments in clinical applications and describe how the mass microscope can be
      employed to assess pathomorphology and pharmacokinetics.

PMID- 22975492
TI  - Membrane perturbations induced by new analogs of neocryptolepine.
AB  - Indoloquinoline alkaloids represent an important class of antimalarial,
      antibacterial and antiviral compounds. Indolo[2,3-b]quinolines are a family of
      DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of
      neocryptolepine, an alkaloid traditionally used in African folk medicine. These
      cytotoxic substances are promising anticancer agents. Active representatives of
      indolo[2,3-b]quinolines affect model and natural membranes. The distinct
      structure and hydrophobicity of the compounds leads to marked differences in the
      disturbing effects on membrane organization and function. Our results also
      indicated a strong relationship between the presence of the chain and the Poct of
      the molecule as well as the capacity for incorporation into carboxyfluorescein
      trapped liposomes in the 0.02-0.06 mM range. Moreover, a correlation between
      binding to neutral dimyristoylphosphatidylcholine (DMPC) or negative charged
      dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DMPC:DMPG, 9:1
      w/w) liposomes, as well as to erythrocyte ghosts and pKa, was also found. All the
      compounds cause hemolysis in isotonic conditions with concentration causing 50%
      hemolysis (HC50) in the 0.12-0.88 mM range. The concentration-dependent
      inhibitory effect of the tested agents on erythrocyte ghosts'
      acetylcholinesterase activity was also studied.

PMID- 22975493
TI  - Protection of apigenin against kainate-induced excitotoxicity by anti-oxidative
      effects.
AB  - Apigenin (5,7,4'-trihydroxyflavone) is a principal ingredient of Cirsium
      japonicum. These experiments were performed to determine whether apigenin has
      neuroprotective effects against kainic acid (KA)-induced excitotoxicity in vitro
      and in vivo. Intraperitoneal (i.p.) administration of apigenin (25, 50 mg/kg)
      decreased the seizure scores induced by KA injection (40 mg/kg, i.p.) in mice. In
      addition, the convulsion onset time was significantly delayed by apigenin
      administration. Moreover, we found that apigenin blocked KA-induced seizure-form
      electroencephalogram (EEG) discharge activity in the brain cortex. In hippocampal
      cells, apigenin inhibited KA-induced excitotoxicity in a dose-dependent manner as
      measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay. To study the possible mechanisms underlying the in vitro
      neuroprotective effects of apigenin against KA-induced cytotoxicity, we also
      examined the effect of apigenin on intracellular reactive oxygen species (ROS)
      elevations in cultured hippocampal neurons and found that apigenin treatment dose
      dependently inhibited intracellular ROS elevation. The remarkable reduction of
      glutathione (GSH) levels induced by KA in hippocampal tissues was reversed by
      apigenin in a dose-dependent manner. In addition, similar results were obtained
      after pretreatment with free radical scavengers such as trolox and
      dimethylthiourea (DMTU). Finally, after confirming the protective effect of
      apigenin in hippocampal CA3 region, we found apigenin is an active compound in KA
      induced neuroprotection. These results collectively indicate that apigenin
      alleviates KA-induced excitotoxicity by quenching ROS as well as inhibiting GSH
      depletion in hippocampal neurons.

PMID- 22975494
TI  - A novel polysaccharide compound derived from algae extracts protects retinal
      pigment epithelial cells from high glucose-induced oxidative damage in vitro.
AB  - Diabetic retinopathy is a common complication of diabetes mellitus (DM). The
      oxidative damage inflicted on retinal pigment epithelial (RPE) cells by high
      glucose closely approximates the molecular basis for the loss of vision
      associated with this disease. We investigate a novel algae-derived polysaccharide
      compound for its role in protecting ARPE-19 cells from high glucose-induced
      oxidative damage. ARPE-19 cells were cultured for 4 d with normal concentration
      of D-glucose, and exposed to either normal or high concentrations of D-glucose in
      the presence or absence of the polysaccharide compound at variety of
      concentrations for another 48 h. Taurine was used as a positive control. Activity
      of super oxide dismutase (SOD) and concentration of glutathione (GSH) were
      measured as well as cytotoxicity of high glucose and the polysaccharide compound.
      To analyse cellular damage by high glucose, activation of Annexin V and p38
      mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase
      (ERK) were examined. Our results showed that a significant cellular damage on
      ARPE-19 cells after 48 h treatment with high glucose, accompanied by a decrease
      in SOD activity and GSH concentration; high glucose also caused ARPE-19 cell
      apoptosis and activation of p38MAPK and ERK. As the non-toxic polysaccharide
      compound protected ARPE-19 cells from high glucose-induced cellular damage, the
      compound recovered SOD activity and concentration of GSH in the cells. The
      compound also abrogated the cell apoptosis and activation of p38MAPK and ERK.
      Therefore, the polysaccharide compound derived from algae extracts could be
      unique candidate for a new class of anti-DM and anti-oxidative damage.

PMID- 22975495
TI  - Spontaneous increases in the fluorescence of 4,5-diaminofluorescein and its
      analogs: their impact on the fluorometry of nitric oxide production in
      endothelial cells.
AB  - We studied the spontaneous increase in the fluorescence intensity of 4,5
      diaminofluorescein. A slow, steady increase in fluorescence continued for at
      least 125 h, and this increase was accompanied by ca. 2 nm red shift in the peak
      of emission spectrum. The spontaneous increase also occurred to diaminorhodamine
      4M and a fluorinated form of diaminofluorescein, which has been also used for the
      detection of nitric oxide (NO). We found that several factors (excitation light,
      pH etc.) did not alter the time course of this increase. Moreover, we found that
      this spontaneous increase can produce false-positive results when measuring low
      rate nitric oxide production in human umbilical vein endothelial cells, and may
      confound the interpretation of results of NO production. We show that this
      adverse effect can be avoided by careful grouping of samples during measurement.

PMID- 22975496
TI  - Phagocytic entry of Legionella pneumophila into macrophages through
      phosphatidylinositol 3,4,5-trisphosphate-independent pathway.
AB  - Legionella pneumophila, a causative agent of Legionnaire's disease, is an
      intracellular pathogen. It intervenes in the signal transduction of macrophages
      by secreting effector molecules through the Icm/Dot type IV secretion system
      (T4SS). There is a connection between signaling cascades that regulate
      phagocytosis and the production of reactive oxygen species (ROS). Class I
      phosphatidylinositol 3-kinase (PI3-K) and its product phosphatidylinositol 3,4,5
      trisphosphate (PI(3,4,5)P3) play key roles in the reorganization of cytoskeleton
      (phagocytosis) and activation of nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase (ROS production). We investigated the production of PI(3,4,5)P3
      and recruitment of class I PI3-K and Rac1 during phagocytosis of L. pneumophila
      by macrophages. Transient recruitment of class I PI3-K as well as PI(3,4,5)P3
      production was observed around a phagocytosed T4SS mutant LELA3118 or avirulent
      mutant 25D in an early stage of infection. In contrast, class I PI3-K was
      recruited while accumulation of PI(3,4,5)P3 was not observed around wild type
      JR32. Immunoglobulin G (IgG)-opsonized live JR32, which would activate class I
      PI3-K through the Fcgamma receptor pathway, did not induce PI(3,4,5)P3
      production. Regardless of whether wild type or mutants were used, transient Rac1
      accumulation was observed around bacteria. These results indicate that the
      phagocytosis of wild type L. pneumophila occurs via a special mechanism in which
      PI(3,4,5)P3 production is absent. This suggests that L. pneumophila may inhibit
      the production of PI(3,4,5)P3, but not the recruitment of class I PI3-K and Rac1,
      in a T4SS-dependent manner. L. pneumophila may start the modulation of host
      signaling cascade immediately after contact with host cells to evade the ROS
      dependent bactericidal system while completing entry into macrophages.

PMID- 22975497
TI  - Blockade of K+ and Ca2+ channels by azole antifungal agents in neonatal rat
      ventricular myocytes.
AB  - Some azole antifungal agents induce long QT syndrome and arrhythmias. Although
      composite functions of ion channels in cardiomyocytes contribute to the shaping
      of action potentials, information on the effects of azole antifungal agents on
      ion currents, except human-ether-a-go-go-related gene (HERG) K+ currents, is
      largely lacking. Using the whole cell patch-clamp technique, we investigated the
      effects of four azole agents (miconazole, ketoconazole, fluconazole, and
      itraconazole) on inward rectifying K+ currents (IKir), voltage-gated L-type Ca2+
      currents (ICaL), and delayed rectifier K+ currents (IKdr) in rat neonate
      ventricular myocytes. Strikingly, miconazole and ketoconazole strongly inhibited
      IKir, IKdr, and ICaL at clinically relevant concentrations. The IC50 values of
      miconazole for IKdr, IKir, and ICaL inhibition were 2.5, 10.4, and 3.0 uM,
      respectively. The IC50 values of ketoconazole for IKdr, IKir and ICaL inhibition
      were 3.2, 20.8, and 3.5 uM, respectively. Fluconazole and itraconazole had
      relatively little effect on ion currents. These findings indicate that miconazole
      and ketoconazole are multiple ion channel inhibitors in cardiomyocytes. We
      suggest that it is necessary to consider this inhibition of ion channels by azole
      agents when assessing cardiovascular side effects.

PMID- 22975499
TI  - Evaluation of basophil CD203c as a predictor of carboplatin-related
      hypersensitivity reaction in patients with gynecologic cancer.
AB  - The incidence of hypersensitivity reaction (HR) to carboplatin has been reported
      to increase after repeated use of the drug. However, a reliable ex vivo test to
      predict HR to carboplatin is not currently available. We evaluated the clinical
      usefulness of measuring basophil CD203c to predict carboplatin-related HR in this
      prospective case-control study conducted at Mie University Hospital between
      October 2009 and September 2010. Eleven patients had history of carboplatin
      related HR within the past 3 years, and 19 had no history of HR after receiving
      more than 5 courses of carboplatin therapy. Six of these 19 patients developed
      carboplatin-related HR during the study period. The CD203c+ basophils (%) and the
      mean fluorescence intensity (MFI) were analyzed on a flow cytometer and compared
      between patients with and without HR. Changes in the CD203c expression on
      basophils before and after HR were also assessed in patients who developed HR
      during the study period. The median CD203c+ basophils (%) and DeltaMFI after 30
      min exposure to 50 ug/mL carboplatin were significantly higher in patients with
      HR (3.5% and DeltaMFI 9.0) compared with those without (2.2% and DeltaMFI 0.4)
      (p<0.05). In particular, these values were significantly higher in patients with
      grade 4 anaphylaxis (10.6% and DeltaMFI 22.0). All five patients who developed
      grade 2-4 anaphylaxis during the study period had high CD203c+ basophils (%)
      and/or increased DeltaMFI on the day before HR. The results suggest that basophil
      CD203c may be a promising biomarker for the prediction of severe carboplatin
      related anaphylaxis.

PMID- 22975498
TI  - Measurement of skin permeation/penetration of nanoparticles for their safety
      evaluation.
AB  - The aim of the present study was to quantitatively evaluate the skin
      permeation/penetration of nanomaterials and to consider their penetration pathway
      through skin. Firstly, penetration/permeation of a model fluorescent
      nanoparticle, Fluoresbrite(r), was determined through intact rat skin and several
      damaged skins. Fluoresbrite(r) permeated through only needle-punctured skin. The
      permeation profiles of soluble high molecular compounds, fluorescein
      isothiocyanate-dextrans (FITC-dextrans, FDs), with different molecular weights
      were also measured for comparison. The effects of molecular sizes and different
      skin pretreatments on the skin barrier were determined on the skin
      penetration/permeation of Fluoresbrite(r) and FDs. Fluoresbrite(r) was not
      permeated the intact skin, but FDs were permeated the skin. The skin distribution
      of titanium dioxide and zinc oxide nanoparticles was also observed after topical
      application of commercial cosmetics. Nanoparticles in sunscreen cosmetics were
      easily distributed into the groove and hair follicles after their topical
      application, but seldom migrated from the groove or follicles to viable epidermis
      and dermis. The obtained results suggested that nanoparticles did not permeate
      intact skin, but permeated pore-created skin. No or little permeation was
      observed for these nanomaterials through the stratum corneum.

PMID- 22975500
TI  - Possibility of alveolar bone promoting enhancement by using lipophilic and/or
      hydrophilic zinc related compounds in zinc-deficient osteoporosis rats.
AB  - The purpose of this research is improvement of therapeutic treatment for
      periodontitis by using lipophilic and/or hydrophilic zinc materials. The sample
      suspension injections were prepared from zinc octanate (C8Zn), zinc stearate
      (C18Zn), zinc sulfate hepta-hydrate (ZnSO4) and tricalcium phosphate (ZnTCP)
      containing 6.17 w/w% zinc. After administrating of all injections to around
      alveolar bone of zinc-deficient osteoporosis rats, plasma Zn concentration, bone
      mineral content (BMC) of jawbone, BMC and bone mechanical strength (BMS) of femur
      and permeability tests for hairless rat stripped skin were measured as
      therapeutic scores. BMC and BMS were measured by using an X-ray computing
      tomography and the three-point bending method, respectively. The body weight,
      plasma Zn concentrations and the area under curve (AUC) for Zn of C8Zn, C18Zn and
      ZnTCP group rats were higher than those of control group, but those of ZnSO4
      group were not changed. BMC of alveolar bone and femur and BMS of femur for C8Zn
      and C18Zn groups for 12 weeks were significantly higher than those of the control
      group, but those of ZnSO4 group were not changed. Stripped rat skin permeability
      treated by the hydrophilic creams containing C8Zn was 5-times higher than that of
      ZnTCP.

PMID- 22975501
TI  - A single-center, randomized, open-label, dose-escalation study to evaluate the
      pharmacokinetics of tacrine analogue octahydrogenacridine succinate tablets in
      healthy Chinese subjects.
AB  - The objectives of the present study were to investigate the pharmacokinetics (PK)
      of tacrine analogue octahydrogenacridine (OHA) succinate tablets in healthy
      Chinese subjects. A single-center, randomized, open-label, dose-escalation study
      was conducted in 42 healthy Chinese subjects. Part I of the study (n=30, 16 male
      and 14 female) evaluated the PK profiles of OHA in healthy Chinese subjects (aged
      18-45 years) after single and multiple doses of 2 mg, 4 mg and 8 mg. Part II
      (n=10) assessed food effect on PK characteristics of OHA. The 10 participants of
      4 mg dose group in part I were given another single dose of 4 mg OHA under fed
      condition. Part III (n=12, 7 male and 5 female) investigate PK behavior of OHA in
      elderly (aged 65-75 years) Chinese healthy subjects. In Part I, following a
      single- and multiple-dose, octahydrogenacridine succinate was rapidly absorbed
      with a median t(max) of 0.67 to 1.00 h, and was eliminated with a mean t1/2 of
      2.27 to 2.98 h in all dose groups and did not appear to be dose dependent. In
      Part II, there were no significant differences in Cmax, AUC0-tn or tmax between 4
      mg single dose fasting group and fed group (p=0.257, 0.153, 0.098, respectively).
      In Part III, both in single-dose and multiple-dose treatment, the main PK
      parameters of OHA in the elderly healthy Chinese subjects showed no statistical
      difference with those of non-elderly group. All these results indicated that OHA
      might be a promising drug under development for Alzheimer's disease (AD) therapy.

PMID- 22975502
TI  - Induction of 1-acylglycerophosphocholine acyltransferase genes by fibrates in the
      liver of rats.
AB  - The effect of fibrates (clofibric acid, bezafibrate and fenofibrate) on the gene
      expression and activity of 1-acylglycerophosphocholine acyltransferase (LPCAT)
      was investigated. The administration of 0.1% (w/w) clofibric acid, bezafibrate or
      fenofibrate in diet for 14 d to rats induced LPCAT activity in hepatic microsomes
      in the following order: fenofibrate>bezafibrate>clofibric acid. The LPCAT induced
      by fenofibrate preferred to arachidonoyl-CoA and linoleoyl-CoA to a greater
      extent than did LPCAT in control microsomes. The treatment with the fibrates
      resulted in upregulation of the relative expression of mRNAs encoding LPCAT3 and
      LPCAT4 in the following order: fenofibrate>bezafibrate>clofibric acid. The
      administration of fibrates did not change the expression of genes encoding either
      LPCAT1 or LPCAT2. The treatment with fibrates elevated relative levels of both
      mRNAs encoding Delta6 desaturase (Fads2) and Delta5 desaturase (Fads1) in the
      order of fenofibrate>bezafibrate>clofibric acid, and the extent of the increase
      in the level of Delta6 desaturase mRNA was greater than that of Delta5
      desaturase. Fatty acid profile in hepatic phosphatidylcholine (PC) was
      significantly changed by the treatments with fibrates. These results suggest (i)
      that fibrates induce LPCAT activity in hepatic microsomes by elevating the
      expression of genes encoding LPCAT3 and LPCAT4, (ii) that the changes in fatty
      acid profile of hepatic PC are, in part, due to the elevated expression of two
      isoforms, LPCAT3 and LPCAT4, and (iii) that the ability of fibrates to induce
      these changes are in the order of fenofibrate>bezafibrate>clofibric acid.

PMID- 22975503
TI  - Meliacinolin: a potent alpha-glucosidase and alpha-amylase inhibitor isolated
      from Azadirachta indica leaves and in vivo antidiabetic property in
      streptozotocin-nicotinamide-induced type 2 diabetes in mice.
AB  - In India, Azadirachta indica is typically known as 'neem tree' and its leaves has
      long been used in the ayurvedic medical tradition as a treatment for diabetes
      mellitus. In-depth chromatographic investigation on chloroform extract resulted
      in identification of one new tetranortriterpenoid. Structural elucidation was
      established on the basis of spectral data as 24,25,26,27-tetranor-apotirucalla
      (apoeupha)-1alpha-senecioyloxy-3alpha,7alpha-dihydroxy-14,20,22-trien-21,23-epoxy
      named by us as meliacinolin (1). The present study investigated the effect
      hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance, alpha
      glucosidase and alpha-amylase of 1 from A. indica. Diabetic rats were treated
      with 1 for 28 d and a set of biochemical parameters were studied including:
      glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and
      muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and
      glutathione reductase. We also looked into liver function by determining glucose
      6-phosphatase, glucokinase and hexokinase activities, and the effect on insulin
      level. While in vitro inhibition of alpha-glucosidase and alpha-amylase enzyme
      activities were used as indices of effect on glucose absorption. As a result we
      found that blood glucose level, serum biochemical parameters, hepatic enzymes,
      thiobarbituric acid reactive substances, and insulin level were restored in
      streptozotocin (STZ)-diabetic mice to normal levels with 1. Meliacinolin
      inhibited alpha-glucosidase and alpha-amylase activities. We conclude that
      meliacinolin can efficiently inhibit insulin resistance, improvement of renal
      function, lipid abnormalities, and oxidative stress, indicating that its
      therapeutic properties may be due to the interaction of meliacinolin with
      multiple targets involved in diabetes pathogenesis. alpha-Glucosidase and alpha
      amylase inhibitors offer an effective strategy to lower the levels of post
      prandial hyperglycemia prevents the digestion of carbohydrates.

PMID- 22975504
TI  - Negative regulation of adipogenesis by kaempferol, a component of Rhizoma
      Polygonati falcatum in 3T3-L1 cells.
AB  - Rhizoma Polygonati falcatum (RPF) has been used as a traditional herbal medicine
      in Asia, because of its anti-hyperglycemic, anti-triglycemic, and anti-tumor
      activity. In this study, we determined the anti-adipogenic potential of RPF
      extract and its component kaempferol in 3T3-L1 adipocytes, and the underlying
      molecular mechanism(s) using microarray analysis. Adipocyte differentiation of
      3T3-L1 cells was significantly impaired by RPF extract and kaempferol as
      monitored by Oil Red O staining and quantitative measurement of lipid
      accumulation. Additionally, the mRNA expression of adipogenesis genes decreased
      on treatment with kaempferol. The role of kaempferol at the genome-wide level was
      further assessed by a microarray approach. Our analysis indicated that kaempferol
      decreased the expression of adipogenic transcription factors (Ppargamma,
      Cebpbeta, Srebp1, Rxrbeta, Lxrbeta, Roralpha) and genes involved in triglyceride
      biosynthesis (Gpd1, Agpat2, Dgat2), while increasing lipolysis-related genes,
      such as Tnfalpha, Lsr, and Cel. Finally, co-transfection assays using luciferase
      reporter gene and reverse transcription-polymerase chain reaction (RT-PCR)
      analysis using peroxisome proliferator-activated receptor-gamma (PPARgamma)
      target genes indicated that kaempferol significantly repressed rosiglitazone
      induced PPARgamma transcriptional activity. Overall, our data suggests that
      kaempferol, a major component of RPF, may be beneficial in obesity, by reducing
      adipogenesis and balancing lipid homeostasis partly through the down-regulation
      of PPARgamma.

PMID- 22975505
TI  - Effects of endogenous proteins and microRNA target sequence in a positive
      feedback system.
AB  - A positive feedback system, using GAL4-vp16 (a fusion protein of yeast GAL4 and
      herpes simplex virus vp16) as an activator and firefly luciferase as a reporter,
      maintained luciferase expression for 7 d in mice. However, the luciferase
      expression decreased after 7 d, and this phenomenon could be caused by
      immunoreactions against these exogenous proteins. This hypothesis was examined by
      the following three strategies, designed to avoid the putative immunoreactions:
      (i) use of the endogenous secreted alkaline phosphatase (SEAP) protein as a
      reporter, (ii) replacement of vp16 with endogenous transcription factors, and
      (iii) insertion of the target sequence of microRNA expressed in cells of
      hematopoietic origin, to suppress GAL4-vp16 expression in antigen-presenting
      cells. The results obtained in this study suggested that silencing would be
      induced by mechanism(s) besides immunoreactions against reporter and activator
      proteins.

PMID- 22975506
TI  - Polyubiquitination of the B-cell translocation gene 1 and 2 proteins is promoted
      by the SCF ubiquitin ligase complex containing betaTrCP.
AB  - B-cell translocation gene 1 and 2 (BTG1 and BTG2) are members of the BTG/Tob
      antiproliferative protein family, which is able to regulate the cell cycle and
      cell proliferation. We previously reported that BTG1, BTG2, Tob, and Tob2 are
      degraded via the ubiquitin-proteasome pathway. In this study, we investigated the
      mechanism of polyubiquitination of BTG1 and BTG2. Since the Skp1-Cdc53/Cullin 1-F
      box protein (SCF) complex functions as one of the major ubiquitin ligases for
      cell cycle regulation, we first examined interactions between BTG proteins and
      components of the SCF complex, and found that BTG1 and BTG2 were capable of
      interacting with the SCF complex containing Cullin-1 (a scaffold protein) and
      Skp1 (a linker protein). As the SCF complex can ubiquitinate various target
      proteins by substituting different F-box proteins as subunits that recognize
      different target proteins, we next examined which F-box proteins could bind the
      two BTG proteins, and found that Skp2, beta-transducin repeat-containing protein
      1 (betaTrCP1), and betaTrCP2 were able to associate with both BTG1 and BTG2.
      Furthermore, we obtained evidence showing that betaTrCP1 enhanced the
      polyubiquitination of both BTG1 and BTG2 more efficiently than Skp2 did, and that
      an F-box truncated mutant of betaTrCP1 had a dominant negative effect on this
      polyubiquitination. Thus, we propose that BTG1 and BTG2 are subjected to
      polyubiquitination, more efficiently when it is mediated by SCFbetaTrCP than by
      SCFSkp2.

PMID- 22975508
TI  - Mechanism of inverse agonist action of sarpogrelate at the constitutively active
      mutant of human 5-HT2A receptor revealed by molecular modeling.
AB  - We previously reported that sarpogrelate, a selective 5-HT2A antagonist, showed a
      potent inverse agonist activity to constitutively active mutant (C322K) of human
      5-HT2A receptor (5-HT2AR). However, it remains to be unknown about the actual
      mechanism of this mutant for its constitutive activation as well as inverse
      agonist activity of sarpogrelate. Our model shows that mutation (C322K) of 5
      HT2AR causes electronic repulsion between positively charged Arg173(3.50) and
      Lys322(6.34) residues resulting outward movement of the C-terminus of
      transmembrane helix (TMH) III. This motion of TMH III leads to a partially active
      structure of the receptor, which may be a key step in receptor activation. The
      structural model of the partially active receptor also indicates that the binding
      of sarpogrelate to the constitutively active receptor causes an inward swing of
      TMH III to an inactive receptor structure. Therefore, the present study may
      suggest that the electronic repulsion causing outward movement of the C-terminus
      of TMH III may be the key step for constitutive activation of mutant C322K of 5
      HT2AR and the inward movement of TMH III causes the inverse agonist activity of
      sarpogrelate.

PMID- 22975509
TI  - The antibacterial activity of compounds isolated from oakmoss against Legionella
      pneumophila and other Legionella spp.
AB  - Oakmoss is a natural fragrance ingredient exhibiting highly specific, potent
      antibacterial activity against Legionella pneumophila, a causative agent of
      severe water-bone pneumonia. In the present study, the antibacterial activity of
      individual compounds isolated from oakmoss was investigated against L.
      pneumophila and other Legionella spp. A total of 18 known compounds and two minor
      novel compounds (i.e., 3-methoxy-5-methylphenyl-2,4-dihydroxy-6-methylbenzoate
      (compound 9) and 8-(2,4-dihydroxy-6-(2-oxoheptyl)-phenoxy)-6-hydroxy-3-pentyl-1H
      isochromen-1-one (compound 20)) were purified from oakmoss. The minimum
      inhibitory concentrations (MICs) against clinical and environmental isolates of
      L. pneumophila, L. bozemanii, L. micdadei, L. longbeachae, and L. dumoffii for 11
      of the 20 compounds were less than 100 ug/mL (range 0.8-64.0 ug/mL). Novel
      compounds 9 and 20 exhibited potent antibacterial activity against L. pneumophila
      strains (MIC ranges of 1.3-8.0 ug/mL and 3.3-13.3 ug/mL, respectively) and also
      against four other Legionella species (MIC ranges of 0.8-8.0 ug/mL and 3.3-21.3
      ug/mL, respectively). Time-kill assays indicated that compounds 9 and 20 kill
      bacteria at a concentration equivalent to 2*MIC after 1 h and 6 h co-incubations,
      respectively. While oakmoss and the purified components exhibited antibacterial
      activity against Legionella spp., they were not active against other Gram
      negative and -positive bacteria such as Escherichia coli, Pseudomonas aeruginosa,
      Bacillus subtilis and Staphylococcus aureus.

PMID- 22975507
TI  - Ginsenoside Rg3 attenuates microglia activation following systemic
      lipopolysaccharide treatment in mice.
AB  - Neuroinflammation, characterized by activation of microglia and expression of
      major inflammatory mediators, contributes to neuronal damage in addition to acute
      and chronic central nervous system (CNS) disease progression. The present study
      investigated the immune modulatory effects of ginsenoside Rg3, a principle active
      ingredient in Panax ginseng, on pro-inflammatory cytokines and microglia
      activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment
      in C57BL/6 mice. Systemic LPS treatment induces immediate microglia activation in
      the brain. Based on this information, ginsenoside Rg3 was treated orally with 10,
      20, and 30 mg/kg 1 h prior to the LPS (3 mg/kg, intraperitoneally (i.p.))
      injection. Ginsenoside Rg3 at 20 and 30 mg/kg oral doses significantly attenuated
      up-regulation of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL
      1beta) and IL-6 mRNA in brain tissue at 4 h after LPS injection. Morphological
      activation of microglia and Iba1 protein expression by systemic LPS injection
      were reduced with ginsenoside Rg3 (30 mg/kg) treatment. In addition, inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in brain
      tissue were also attenuated with oral treatment of ginsenoside Rg3 at 30 mg/kg.
      These results indicate that ginsenoside Rg3 plays a modulatory role in
      neuroinflammation. This study shows that ginsenoside Rg3 attenuates microglia
      activation using an in vivo animal model.

PMID- 22975510
TI  - Anti-apoptotic function and mechanism of ginseng saponins in Rattus pancreatic
      beta-cells.
AB  - Apoptosis is the main form of beta-cell death in diabetes. Ginseng has been used
      as an anti-diabetic herb for several thousand years in Asia with ginsenoside Rg1
      and ginsenoside Rb1 as important active ingredients. In this study, we
      demonstrated ginsenoside Rg1 and Rb1 protect beta-cells from high
      glucose/cytokine-induced pancreatic beta-cell apoptosis via inhibiting nitric
      oxide (NO) production and regulating apoptosis-related genes. Among these genes,
      Bax, Fas and Caspase-3 gene expressions were up-regulated by high glucose,
      whereas only Bax and Caspase-3 gene expression were elevated by cytokines. In
      these two stimuli-induced apoptotic cells, Rg1 down-regulated Fas gene
      expression, while Rb1 decreased Caspase-3 gene expression. As a conclusion, Fas
      signal pathway and mitochondria stress is mostly related to anti-diabetes
      function of ginsenoside Rg1, while Caspase-3 pathway is essential when Rb1 is
      present.

PMID- 22975511
TI  - Hepatoprotective effects of the polysaccharide isolated from Tarphochlamys
      affinis (Acanthaceae) against CCl4-induced hepatic injury.
AB  - This study was designed to investigate the protective effects of the
      polysaccharide isolated from Tarphochlamys affinis (PTA) against CCl4-induced
      hepatotoxicity in rats. Liver injury was induced in rats by the administration of
      CCl4 twice a week for 2 weeks. During the experiment, the model group received
      CCl4 only; the treatment groups received various drugs plus CCl4, whereas the
      normal control group received an equal volume of saline. Compared with the CCl4
      group, PTA significantly decreased the activities of aspartate aminotransferase
      (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the serum
      and increased the activities of superoxide dismutase (SOD), glutathione
      peroxidase (GPx) in the liver. Moreover, the content of hepatic malondialdehyde
      (MDA) was reduced. Histological findings also confirmed the anti-hepatotoxic
      characterisation. In addition, PTA significantly inhibited the proinflammatory
      mediators, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase
      (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumour necrosis factor
      alpha (TNF-alpha) and myeloperoxidase (MPO). Further investigation showed that
      the inhibitory effect of PTA on the pro-inflammatory cytokines was associated
      with the down-regulation of nuclear factor-kappa B (NF-kappaB). In brief, our
      results show that the protective effect of PTA against CCl4-induced hepatic
      injury may rely on its ability to reduce oxidative stress and suppress
      inflammatory responses.

PMID- 22975512
TI  - The rhizomes of Alisma orientale and alisol derivatives inhibit allergic response
      and experimental atopic dermatitis.
AB  - The 70% ethanol extract of the rhizome of Alisma orientale (Alismatis rhizome)
      (AOE) was prepared and found to significantly inhibit 5-lipoxygenase (5-LOX)
      catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells
      and beta-hexosaminidase release by antigen-stimulated RBL-2H3 cells. It also
      attenuated delayed-type hypersensitivity (DTH) reaction in mice. Among the three
      major triterpene constituents isolated (i.e., alisol B, alisol B 23-acetate,
      alisol C 23-acetate) as active principles, alisol B and its 23-acetate strongly
      and significantly inhibited LT production and beta-hexosaminidase release between
      1-10 uM. On the other hand, all these alisol derivatives significantly and
      strongly inhibited DTH response after oral administration. In addition, AOE (200
      mg/kg/d) was for the first time found to considerably alleviate hapten-induced
      dermatitis symptoms in NC/Nga mice, an animal model of atopic dermatitis. These
      results indicate that alisol derivatives possess inhibitory activities on
      immediate-type as well as delayed-type hypersensitivity reactions and may
      contribute to the anti-allergic action of AOE.

PMID- 22975513
TI  - Interferon gamma induces steroid sulfatase expression in human keratinocytes.
AB  - Steroid sulfatase (STS) plays an important role in steroid metabolism in which
      estrogens and dehydroepiandrosterone (DHEA) are produced from their sulfates.
      However, little is known about the transcriptional regulation of the STS gene in
      keratinocytes. Since keratinocytes are thought to be a primary target of
      interferon gamma (IFNgamma) in inflammatory and immune responses, we assessed the
      effects of this cytokine upon STS gene expression in the human keratinocyte cell
      line SVHK and in normal human keratinocytes (NHEK). Stimulation of SVHK cells
      with 50 ng/mL of IFNgamma for 24 h induced an approximately three-fold increase
      in STS activity and in its mRNA levels compared to non-treated cells. IFNgamma
      treatment also induced an approximately 1.5-fold increase in STS mRNA levels in
      NHEK cells. This induction was completely inhibited by treatment with
      phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, and
      by the nuclear factor-kappa B (NF-kappaB) inhibitor,
      dehydroxymethylepoxyquinomicin (DHMEQ). These data suggest that activation of the
      PI 3-kinase signal transduction pathway mediates induction of STS gene expression
      by IFNgamma through activation of NF-kappaB. The anti-inflammatory agent
      dexamethasone inhibited IFNgamma induction of STS gene expression, suggesting
      involvement of a glucocorticoid receptor in the regulation of STS gene expression
      in keratinocytes. Regulation of STS gene expression in skin as a novel target of
      drugs for therapy of psoriasis in the skin is discussed.

PMID- 22975514
TI  - Inhibition of human steroidogenic cytochrome P450 c17 by 21-hydroxypregnenolone
      and related steroid hormones.
AB  - The effects of 21-hydroxypregnenolone and related steroids such as
      deoxycorticosterone (DOC; 21-hydroxyprogesterone), cortisol, and corticosterone
      on progesterone 17alpha-hydroxylase activity by steroidogenic cytochrome P450 c17
      (CYP17) were investigated. 21-Hydroxypregnenolone contains a hydroxyl group at C3
      in the A cyclic hydrocarbon ring and a double bond at C5 in the B cyclic
      hydrocarbon ring, whereas DOC, cortisol, and corticosterone contain a ketone
      group at C3 and a double bond at C4 in the A cyclic hydrocarbon ring. No marked
      inhibition was observed for DOC, cortisol, and corticosterone at 100 MUM
      concentration. Nonetheless, 21-hydroxypregnenolone exhibited competitive
      inhibition of progesterone 17alpha-hydroxylation activity by CYP17 with a Ki
      value of 36.4 uM. These results suggest that a hydroxyl group at C3 in the A ring
      and a double bond at C5 in the B ring in steroid hormones are important for the
      substrate recognition of CYP17.

PMID- 22975515
TI  - 9,10-phenanthrenequinone induces monocytic differentiation of U937 cells through
      regulating expression of aldo-keto reductase 1C3.
AB  - Persistent inhalation of diesel exhaust particles results in damaged lung cells
      through formation of reactive oxygen species (ROS), but the details of the
      toxicity mechanism against monocytes are poorly understood. In this study, we
      used human promyelomonocytic U937 cells as surrogates of monocytes and
      investigated the toxicity mechanism initiated by exposure to 9,10
      phenanthrenequinone (9,10-PQ), a major quinone component in diesel exhaust
      particles. A 24-h incubation with 9,10-PQ provoked apoptotic cell death, which
      was due to signaling through the enhanced ROS generation and concomitant caspase
      activation. Flow cytometric analyses of U937 cells after long-term exposure to
      9,10-PQ revealed induction of differentiation that was evidenced by increasing
      expression of CD11b/CD18, a cell-surface marker for monocytic differentiation
      into macrophages. The 9,10-PQ-induced differentiation was significantly abolished
      by ROS inhibitors, suggesting that ROS generation contributes to cell
      differentiation. The 9,10-PQ treatment increased the expression of aldo-keto
      reductase (AKR) 1C3, which reached a peak at 1 to 2 d post-treatment and then
      declined. The bell-shaped curve of the AKR1C3 expression by 9,10-PQ resembled
      that caused by phorbol 12-myristate 13-acetate, a differentiation inducer.
      Additionally, the concomitant treatment with tolfenamic acid, a selective AKR1C3
      inhibitor, sensitized the differentiation induced by 9,10-PQ. These results
      suggest that ROS formation during 9,10-PQ treatment acutely leads to apoptosis of
      U937 cells and the initiation of monocytic differentiation, which proceeds after
      the provisional overexpression of AKR1C3.

PMID- 22975516
TI  - Detoxification of 6-hydroxydopamine-induced dopaminergic neurodegeneration by 5,5
      dimethyl-1-pyrroline N-oxide, a radical trapper, in hemiparkinsonian rats.
AB  - Several useful spin trap agents have been identified for the identification and
      quantification of biological oxygen radicals. Among them, 5,5-dimethyl-1
      pyrroline N-oxide (DMPO) has been used most frequently as a spin trap agent. The
      function of DMPO in vivo, however, is still unclear. Thus, the purpose of this
      study was to evaluate the effect of DMPO in an in vivo model of Parkinson's
      disease (PD). Rats were microinjected with 6-hydroxydopamine (6-OHDA, 32 nmol) in
      the presence or absence of DMPO (0.4, 4 nmol). We investigated behavioral and
      histochemical parameters in this rat model of PD. In addition, to examine the
      effect of DMPO against oxidative stress, we performed an electron spin resonance
      (ESR) analysis. Intranigral injection of 6-OHDA alone caused behavioral
      dysfunction and a massive loss of tyrosine hydroxylase (TH)-positive neurons in
      the substantia nigra pars compacta (SNpc). Co-microinjection of 4 nmol DMPO, but
      not 0.4 nmol, significantly prevented 6-OHDA-induced behavioral impairments and
      dopaminergic neurodegeneration. In ESR analysis, DMPO directly trapped hydroxyl
      radical (.OH) generated from 6-OHDA and Fe2+ in a concentration-dependent manner.
      These results suggest that DMPO attenuates 6-OHDA-induced dopaminergic
      neurodegeneration in a rat model of PD via scavenging .OH, and is a useful tool
      for biological research of oxidative stresses.

PMID- 22975517
TI  - Development of an immunohistochemical protein quantification system in
      conjunction with tissue microarray technology for identifying predictive
      biomarkers for phosphatidylinositol 3-kinase inhibitors.
AB  - The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human
      cancers by gain-of-function mutations of phosphoinositide-3-kinase, catalytic,
      alpha polypeptide (PIK3CA) or dysfunction of phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN). Therefore PI3K is thought to be a promising
      target for cancer therapy. Many agents targeting PI3K have been developed and
      some of them have been evaluated in clinical trials. In recent years, development
      of predictive biomarkers as companion diagnostics for molecular targeted drugs
      has become an important requirement for clinical development; however, no
      clinically established biomarkers that predict the efficacy of PI3K inhibitors
      have been found. We previously reported that expression of phosphorylated Akt
      determined by immunoblot analysis correlated with the antitumor efficacy of a
      PI3K inhibitor ZSTK474 in vitro and in vivo, suggesting that it might be used as
      a predictive biomarker. In this study, to evaluate biomarker candidates in in
      vivo tumor samples, we developed an immunohistochemical protein
      detection/quantification system in conjunction with the tissue microarray
      technology using a panel of 24 human tumor xenografts (JFCR24). We have clearly
      demonstrated that expression levels of phosphorylated v-akt murine thymoma viral
      oncogene homolog (Akt) and mitogen-activated protein kinase (MAPK) determined by
      this system significantly correlated with those determined by immunoblot
      analysis. As expected, PTEN status correlated with expression of phosphorylated
      Akt but not MAPK. Finally, we confirmed that phosphorylated Akt levels determined
      using this system correlated with the in vivo efficacy of ZSTK474. The present
      results indicate that the immunohistochemical protein detection/quantification
      system could be used to quantify expression of biomarker proteins in xenografted
      tumor tissues as well as in human tumor specimens to predict drug efficacy in
      future clinical trials.

PMID- 22975519
TI  - [Not Available].

PMID- 22975518
TI  - Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the
      AMP-activated protein kinase signaling pathway.
AB  - Colon cancer is the third most common malignancy around the world. Surgery,
      chemotherapy, and radiotherapy are generally used to treat colon cancer, but no
      effective therapy for advanced colon carcinoma is available. Therefore, there is
      a need to identify other therapeutic agents against this disease. Magnolol, a
      hydroxylated biphenyl compound present in Magnolia officinalis, exerts anticancer
      potential and low toxicity. Emerging evidence has suggested that activation of
      AMP-activated protein kinase (AMPK), a potential cancer therapeutic target is
      involved in apoptosis in colon cancer cells. However, the effects of magnolol on
      human colon cancer through activation of AMPK remain unexplored. In this study,
      we explored whether magnolol exerts an antiproliferative effect, and induces
      apoptosis in HCT-116 human colon cancer cells. Magnolol displayed several
      apoptotic features, including propidium iodide labeling, DNA fragmentation, and
      caspase-3 and poly(ADP-ribose) polymerase cleavages. We showed that magnolol
      induced the phosphorylation of AMPK in dose- and time-dependent manners. The
      selective AMPK inhibitor compound C abrogated the effect of magnolol on AMPK
      activation, suppression of proliferation, and caspase-3 cleavage. Magnolol
      downregulated expression of the antiapoptotic protein Bcl2, upregulated
      expression of pro-apoptotic protein p53 and Bax, and caused the release of
      mitochondrial cytochrome c. Magnolol-induced p53 and Bcl2 expression was
      abolished in the presence of compound C. Magnolol inhibited migration and
      invasion of HCT-116 cells through AMPK activation. These findings demonstrate
      that AMPK mediates the anticancer effects of magnolol through apoptosis in HCT
      116 cells.

PMID- 22975520
TI  - Treatment of differentiated thyroid carcinoma: a survey.
AB  - INTRODUCTION: In January 2005, during the annual meeting of the Portuguese
      Society of Endocrinology, Diabetes and Metabolism, a questionnaire on the
      treatment and follow-up of differentiated thyroid carcinoma (DTC) was given to
      attendants. The aim of this study was to present the survey's results. METHODS:
      The questionnaire addressed the following issues: the surgical treatment of the
      gland and cervical lymph nodes, whole body scan and ablation with (131)I,
      suppression with levothyroxine, and treatment of recurrence and metastases. Fifty
      four completed questionnaires were obtained (79% from clinical endocrinologists).
      RESULTS: When DTC is diagnosed, 67% of respondents reported that total
      thyroidectomy is always performed. When the diagnosis is made postsurgically,
      completion of thyroidectomy is recommended by 70% of respondents for papillary
      carcinoma, by 67% for papillary microcarcinoma and by 44% for minimally invasive
      follicular carcinoma. Most respondents recommend lymph node dissection if the
      nodes are involved; 61% systematically perform whole body scan with (131)I after
      surgery. Twenty-eight percent routinely perform ablation of the thyroid, and 59%
      request adjuvant radioiodine ablation of the thyroid bed if there is (131)I
      uptake, if thyroglobulin is increased, or if risk factors are present. The most
      commonly used ablation dose is 100 mCi. Consensus on the degree of TSH
      suppression is lacking. Twenty-two percent of the respondents recommend surgery
      as the first therapeutic option in recurrence and metastases, while 57% prefer
      (131)I for the treatment of local recurrence. When thyroglobulin levels remain
      high and the results of (131)I scanning are negative, 50% choose computed
      tomography scan for the diagnosis of disease recurrence. CONCLUSIONS: The wide
      variability of responses in this survey and the significant percentage (11 to
      41%) of non-responders demonstrates the lack of uniformity in the treatment
      protocols for DCT in Portugal. According to the published guidelines and the
      responses to a similar survey performed in Spain, the widest differences are
      mainly found in lymph node dissection and the treatment of disease recurrence.

PMID- 22975521
TI  - Management of diabetic ketoacidosis in children and adolescents.
AB  - Diabetic ketoacidosis (DKA) is present in nearly half of all diabetic children
      and adolescents at diagnosis. The incidence is 4.6 to 8 cases/1000 diabetics per
      year. DKA is a major cause of mortality and morbidity, which can only be reduced
      by appropriate treatment. The present article describes the physiopathology and
      clinical manifestations of DKA and discusses the management of this entity.

PMID- 22975522
TI  - Panhypopituitarism due to craniopharyngioma associated with hyperthyroidism
      caused by graves' disease.
AB  - Craniopharyngiomas are unusual tumors that are mainly located in the sella
      turcica or parasellar structures. These tumors can produce multiple neurological
      and visual symptoms or manifestations due to involvement of the hypothalamic
      pituitary axis. Pituitary manifestations can be produced by involvement of the
      anterior or posterior pituitary and contribute to the substantial morbidity and
      mortality associated with these tumors, despite their benign histology. We
      present the case of a woman with a craniopharyngioma that produced
      panhypopituitarism and diabetes insipidus, in whom diagnosis was hampered by the
      development of primary hyperthyroidism due to Graves' disease during the
      diagnostic process.

PMID- 22975524
TI  - Levothyroxine therapy and imatinib.
AB  - Levothyroxine requirements in patients with hypothyroidism are usually stable.
      Consequently, thyroid function is usually monitored once or twice yearly.
      Occasionally, the dose of levothyroxine can be changed by pharmacological
      reactions. We report the case of a 59-year-old woman who was under levothyroxine
      therapy for hypothyroidism secondary to subtotal thyroidectomy, with clinical and
      biochemical euthyroidism, who required an increased dose of levothyroxine after
      starting imatinib therapy. The patient was diagnosed with chronic myeloid
      leukemia and imatinib therapy was started. Subsequently, we observed clinical and
      biochemical hypothyroidism, requiring an increase in levothyroxine dose. Some
      cases of hypothyroidism after initiation of imatinib therapy in patients with
      levothyroxine replacement therapy have recently been published. Our case provides
      further evidence of a reaction between the two drugs. Therefore, we discuss the
      most likely physiopathological mechanisms contributing to imatinib-induced
      hypothyroidism in patients under levothyroxine replacement therapy.

PMID- 22975523
TI  - Parasitic thyroid nodule in hashimoto's thyroiditis.
AB  - We present a case of parasitic thyroid nodule in a 62-year-old woman with
      Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy for a 15
      mm nodule suspicious for malignancy. A recurrential ipsilateral lymph nodule was
      identified and removed. Conclusive histopathologic study confirmed that the mass
      was an extracapsular thyroid nodule (parasitic nodule).

PMID- 22975525
TI  - Hemiballism due to hyperglycemic hyperosmolar syndrome.
AB  - Non-ketotic hyperglycemia has occasionally been associated with various
      neurological abnormalities including movement disorders. Hyperglycemic
      hyperosmolar syndrome (HHS) is the second most common cause of hemiballism
      hemichorea, which is due to a contralateral putaminal lesion. We describe a 95
      year-old woman with HHS who developed hemichorea-hemiballism syndrome due to a
      putaminal lesion.

PMID- 22975526
TI  - [Not Available].

PMID- 22975527
TI  - Functional analysis of misfolded transthyretin extracted from abnormal vitreous
      with high myopia related ocular pathologies.
AB  - BACKGROUND: In the development of high myopia, some secondary ocular diseases
      such as macular detachment (MD) and macular hole (MH) may occur owing to the
      elongation of the eyeball. Higher concentrations of misfolded transthyretin (TTR)
      had been detected in abnormal vitreous humor, but the mechanisms are still
      unclear. METHOD: TTRs of high myopia and healthy vitreous were purified with TTR
      polyclonal antibody-Sepharose. Gel exclusion chromatography, cleavage activity
      assay and a fluorescent probe were employed for the functional comparison of
      natural and abnormal TTRs. RESULTS: Compared with natural transthyretin, MH TTR
      showed lower retinol-binding protein (RBP) binding ability; and MD TTR could not
      bind with RBP at all. Additionally, MH and MD TTR did not reveal cleavage
      activity against apolipoprotein AI (apoA-I). Furthermore, the kinetic parameters
      of the interactions between abnormal TTRs and a thyroxine-like fluorescent probe
      were quite different from those of natural TTR. CONCLUSIONS: The results
      suggested that misfolded TTRs in MD and MH patients' vitreous completely or
      partially lost natural bio-functions; and this should be associated with abnormal
      high TTR levels.

PMID- 22975528
TI  - Overexpression and clinical significance of carcinoembryonic antigen-related cell
      adhesion molecule 6 in colorectal cancer.
AB  - BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6)
      inhibits anoikis and affects the malignant phenotype of cancer cells. In this
      study, we analyzed CEACAM6 as a gene that is highly upregulated in colon cancer
      tissues, and examined the assertion that CEACAM6 might be a suitable candidate
      tumor marker for the diagnosis of colon cancer. METHODS: CEACAM6 gene expression
      in human colon tissues was performed by tissue microarray and analyzed using RT
      PCR (each of normal and tumor tissue, n=40) and immunohistochemical and
      clinicopathological (colon cancer patients, n=143) analyses. RESULTS: CEACAM6
      transcriptional and translational levels were significantly upregulated in human
      tumor tissues compared to non-tumor regions, and clinicopathological analysis
      revealed a significant correlation between CEACAM6 protein expression and Dukes'
      stage (p<0.001). High expression levels of CEACAM6 were significantly associated
      with lower overall survival (p<0.001) and shorter recurrence-free survival
      (p<0.001). We demonstrated that knockdown of CEACAM6 with CEACAM6-specific small
      interfering RNA in colorectal cancer cells attenuated invasivity (35%);
      conversely, the overexpression of CEACAM6 increased invasiveness. CONCLUSIONS:
      CEACAM6 is significantly upregulated in colon cancer tissues and is closely
      associated with poor prognosis, indicating that CEACAM6 might be used as a tumor
      biomarker and a potential therapeutic target for colon cancer.

PMID- 22975529
TI  - Vitamin D in exercise: physiologic and analytical concerns.
AB  - Despite a wide number of studies performed on the general population, little is
      known about the Vitamin D status of athletes. A particular influence of many
      factors, including skin pigmentation, early- or late-day training, indoor
      training, geographic location and extensive sunscreen use, has been observed in
      this specific population. The need of supplementation with Vitamin D in athletes
      is not defined or, when supplementation is needed, even the optimal amount of
      Vitamin D to be used is not specified. The periodic measurement of Vitamin D is
      the only procedure capable to define athletes' status. Although various methods
      for the measurement of Vitamin D are routinely used, they often give discordant
      and poorly reproducible results; thus, it is necessary to standardize the various
      methods, in order to have comparable results. In conclusion, current available
      data indicate both that little is known about the Vitamin D status of athletes
      and that is still unclear if supplementation could be desirable. Finally, it must
      be pointed out that all the papers about Vitamin D status should indicate in
      detail the method used for really allowing a correct interpretation of data.

PMID- 22975530
TI  - Current analytical strategies for C-reactive protein quantification in blood.
AB  - The measurement of serum C-reactive protein (CRP) levels has been given
      particular interest as a marker of inflammation associated with cardiovascular
      diseases. CRP belongs to the pentraxin family of proteins and the routine
      clinical analysis of CRP in blood samples is used as an important factor in
      primary prevention programmes together with causative and predisposing factors.
      This review focuses on the most representative methodologies and strategies for
      CRP detection and quantification that have been recently proposed, as well as
      reviewing those that are currently being developed for the specific, sensitive,
      inexpensive and high-throughput blood analysis of this protein.

PMID- 22975532
TI  - Do electrocardiography scores predict the presence of right ventricular
      dysfunction in patients with pulmonary hypertension?

PMID- 22975531
TI  - Variation in clinical vitamin D status by DiaSorin Liaison and LC-MS/MS in the
      presence of elevated 25-OH vitamin D2.
AB  - BACKGROUND: We compared total 25-OH vitamin D status measured by DiaSorin Liaison
      and tandem mass spectrometry (LC-MS/MS) among patients with high and low 25-OH
      vitamin D(2). METHODS: Total 25-OH vitamin D was measured in plasma containing
      high (>25 nmol/l or >50%, n=26) and low (<2.5 nmol/l, n=29) 25-OH vitamin D(2)
      using DiaSorin Liaison and an LC-MS/MS method using NIST 972-verified
      calibrators. Samples were classified as vitamin D adequate (total 25-OH vitamin D
      >=50 nmol/l), and inadequate or deficient (<50 nmol/l) by each method. Deming and
      multiple linear regression were used to compare methods. RESULTS: Samples were
      significantly more likely to be classified as inadequate or deficient by DiaSorin
      Liaison (36%) vs LC-MS/MS (9%). This increased in the presence of high 25-OH
      vitamin D2 (42% vs 0%). Total 25-OH vitamin D by DiaSorin Liaison was 26.0 nmol/l
      lower than LC-MS/MS, which increased to 34.1 nmol/l among samples with high 25-OH
      vitamin D(2). This was attributed to lower recovery of 25-OH vitamin D(2)
      (proportional bias=0.64 nmol/l) by DiaSorin Liaison, independent of D(3)
      (proportional bias=0.86 nmol/l). CONCLUSIONS: Patients were more likely to be
      classified as vitamin D inadequate or deficient by DiaSorin Liaison compared to
      an LC-MS/MS method, which was in part due to the presence of 25-OH vitamin D(2).

PMID- 22975533
TI  - Leg heating using far infra-red radiation in patients with chronic heart failure
      acutely improves the hemodynamics, vascular endothelial function, and oxidative
      stress.
AB  - BACKGROUND: Systemic thermal therapy (STT) has been associated with beneficial
      effects in patients with chronic heart failure (CHF). The fact, however, that it
      requires a dedicated as well as spacious facility and trained personnel makes it
      difficult to practice in the daily care of patients with CHF. OBJECTIVE: The aim
      of this study was to determine whether the leg thermal therapy (LTT) has a
      positive impact similar to that of STT in patients with CHF. Methods and Results
      Twenty patients with CHF (57 +/- 17 years old, left ventricular ejection
      fraction=30 +/- 10%) received LTT (45 degrees C) for 20 minutes. Immediately
      after the treatment, the core temperature had increased (+0.3 +/- 0.3 degrees C)
      (p<0.01). While the LTT had no significant effects on the heart rate, systolic
      arterial pressure, and diastolic blood pressure, it increased the cardiac output
      (mixed venous oxygen saturation; +2 +/- 3%) and decrease the pulmonary capillary
      wedge pressure (-2 +/- 2 mmHg). The LTT significantly improved the flow-mediated
      vasodilatation (FMD) from 4.8 +/- 2.6 to 7.1 +/- 3.6%, the antioxidative markers,
      thiol from 4.0 +/- 0.7 to 4.5 +/- 0.9 MUmoL/g, and the marker of oxidative
      deoxyribonucleic acid (DNA) damage, urine 8-hydroxy-2'deoxyguanosine (8OHdG) from
      100 to 82 +/- 3%, respectively (p<0.05). No patient had any adverse effects
      associated with LTT. Conclusion LTT acutely improved FMD, and oxidative stress in
      patients with CHF. Although the long-term effect of LTT remains to be
      investigated, its practicality which is comparable to that of STT would make it
      an attractive therapeutic strategy for patients with CHF.

PMID- 22975534
TI  - Red blood cell distribution width as an effective tool for detecting fatal heart
      failure in super-elderly patients.
AB  - OBJECTIVE: Red blood cell distribution width (RDW) is a numerical measure of
      erythrocyte size variation. It has been recently reported to be an independent
      prognostic marker of heart failure (HF). Previous studies on RDW were mostly
      designed for middle-aged and elderly patients (60-79 years old), therefore, there
      is no established limit for super-elderly patients (>= 80 years old). The purpose
      of this study was to evaluate RDW as an effective tool to detect fatal HF in
      super-elderly patients. METHODS: The medical records and death certificates of
      160 consecutive patients admitted to the Department of Cardiology in Juntendo
      Tokyo Koto Geriatric Medical Center and who died from June 2002 to October 2010
      were reviewed. The causes of death were reviewed, and the factors, including RDW,
      that might have been related to the fatal HF were evaluated using multivariate
      logistic regression analysis. RESULTS: HF was the major cause of death [52
      patients (32.5%), 29 females, age 84.0 +/- 7.5 years], followed by pneumonia
      (18.8%, 30/160), and acute myocardial infarction (16.3%, 26/160). The most common
      cause of HF was atrial fibrillation (36.6%, 19/52), followed by hypertensive
      heart disease (19.2%, 10/52) and valvular disorders (17.3%, 9/52). The
      multivariate logistic regression analysis found that a high RDW (>= 16.5%) was an
      independent factor related to fatal HF (OR 2.36, 95% CI 1.10, 5.04, p=0.03).
      CONCLUSION: HF was the major cause of death, and RDW >= 6.5 was significantly
      associated with fatal HF in super-elderly patients.

PMID- 22975535
TI  - Significance of electrocardiographic right ventricular hypertrophy in patients
      with pulmonary hypertension with or without right ventricular systolic
      dysfunction.
AB  - OBJECTIVE: We sought to determine the value of electrocardiographic right
      ventricular hypertrophy (ECG-RVH) in pulmonary hypertension (PH) patients with
      right ventricular systolic dysfunction defined by cardiac magnetic resonance (CMR
      RVSD). PATIENTS: A total of 31 consecutive patients with PH with a mean pulmonary
      arterial pressure of >25 mmHg underwent both ECG and CMR studies. Patients were
      divided into 2 groups according to the presence of RVSD, defined as a RV ejection
      fraction <35%. Logistic regression modeling was performed to define the
      association between ECG-RVH and CMR-RVSD. RESULTS: About half of the patients had
      RVSD (n=15 ; 48%). The R to S wave ratio (p=0.01) or incidence of qR pattern
      (p=0.002) in lead V(1) was significantly greater in patients with PH complicated
      by RVSD than in those without RVSD. These 2 patterns were significant predictors
      of RVSD [odds ratio (OR), 19.3 for qR; OR, 14.0 for R/S>1] and when each of these
      ECG findings was assigned with a point proportional to OR (score of 2 for qR in
      lead V(1) and score of 1 for R/S>1 in lead V(1)), the incidence of RVSD increased
      by the total ECG score. CONCLUSION: The combination of ECG-RVH findings,
      especially in lead V(1), predicts the presence of RVSD defined by CMR. ECG might
      be a useful tool for estimating the presence of RVSD in patients with PH.

PMID- 22975536
TI  - Short-term effects of beta-adrenergic antagonists and methimazole in new-onset
      thyrotoxicosis caused by Graves' disease.
AB  - OBJECTIVE: beta-adrenergic antagonists (beta-blockers) are often used to
      attenuate the hyperadrenergic symptoms of Graves' disease (GD), including
      palpitation. Although beta-blockers reduce the heart rate, cardiac output and
      oxygen consumption, no firm evidence exists regarding the effects of combined
      therapy with beta-blockers and anti-thyroid drugs. The objective is to elucidate
      the effects of beta-blockers on anti-thyroid drug therapy in GD. METHODS:
      Patients newly diagnosed with mild GD were randomly assigned to receive
      methimazole with or without beta-blockers in a prospective multi-center survey.
      The heart rate and thyroid function were measured and the quality of life was
      assessed using original and SF-36 questionnaires at 0 and 4 weeks. RESULTS: A
      total of 28 patients were enrolled in the study. Fourteen patients (one man, 13
      women) were randomly assigned to the group treated with beta-blockers and 14
      patients (one man, 13 women) were randomly assigned to the group not treated with
      beta-blockers. Although no significant differences in the improvement of thyroid
      function were observed between the two groups, the heart rates improved more
      significantly in the group treated with beta-blockers. Specific symptoms, such as
      easy fatigability and shortness of breath, also improved more significantly with
      the beta-blocker treatment. In addition, 'physical functioning' assessed with the
      SF-36 questionnaires significantly improved only in the group treated with beta
      blockers. CONCLUSION: Although beta-blockers may not reinforce the effects of
      anti-thyroid drugs on thyroid function, at least during the course of one month,
      they are effective in reducing heart rates and ameliorating specific symptoms in
      patients with mild GD.

PMID- 22975537
TI  - Relationships of decreased lung function with metabolic syndrome and obstructive
      sleep apnea in Japanese males.
AB  - OBJECTIVE: Decreased lung function as assessed by forced vital capacity (FVC) and
      forced expiratory volume in one second (FEV(1)) is shown to be associated with
      cardiovascular morbidity and mortality. Although the underlying mechanisms for
      this association remain unknown, metabolic syndrome and obstructive sleep apnea
      (OSA) may have a role. We analyzed the relationships between metabolic syndrome
      and OSA in a cross-sectional health survey of middle-aged male employees.
      METHODS: In this secondary analysis, we re-analyzed the relationships of lung
      function determined by spirometry with metabolic syndrome and OSA based on the
      respiratory disturbance index (RDI) with a type 3 portable monitor. RESULTS: We
      analyzed 273 subjects. Independent of age, body mass index (BMI) and smoking,
      quartiles for lower FVC and FEV(1) were associated with a higher risk of
      metabolic syndrome compared with quartiles for the highest FVC and FEV(1),
      respectively. A similar trend was observed regarding the risk associated with
      waist circumference, and in FVC cases, dyslipidemia. The risk of hyperglycemia
      was significantly higher in quartiles for the second lowest FVC and FEV(1) than
      in quartiles for the highest FVC and FEV(1), respectively. A significant trend
      for an increase in RDI was observed in accordance with quartiles for lower FVC,
      but not FEV(1). CONCLUSION: There was a significant relationship between lung
      function impairment and metabolic syndrome through mainly abdominal obesity,
      partially through hyperglycemia, and also through dyslipidemia, but only with
      respect to restrictive lung function. Restrictive lung function was also related
      to OSA. This epidemiologic evidence may indicate underlying mechanisms between
      decreased lung function and cardiovascular risk.

PMID- 22975538
TI  - Dexmedetomidine versus midazolam for the sedation of patients with non-invasive
      ventilation failure.
AB  - OBJECTIVE: To compare the efficacy and safety of sedation with dexmedetomidine
      vs. midazolam for patients with acute cardiogenic pulmonary edema and hypoxemia
      during the treatment of non-invasive ventilation (NIV). METHODS: The intensive
      care unit (ICU) patients treated in our hospital between March 2008 and August
      2011 who had acute pulmonary edema and hyoxemia in NIV failure due to patient
      refusal to continue the NIV sessions (due to discomfort) were enrolled in this
      study. The patients were divided into two groups by the random numerical table
      method. They were treated with either midazolam (29 cases) or dexmedetomidine (33
      cases). The patients were sedated (Ramsay scale 2-3) by a continuous perfusion of
      midazolam or dexmedetomidine during the NIV session. Cardiorespiratory and
      ventilatory parameters, the results of the blood gas analysis, and adverse events
      were prospectively recorded. The main outcome measure was the percentage of
      endotracheal intubation during NIV. Secondary endpoints included the duration of
      non-invasive mechanical ventilation, length of ICU stay, and adverse events.
      RESULTS: In both groups of patients, the expected sedative scores were obtained.
      The cardiorespiratory symptoms and signs (oxygenation index, pH value, and
      respiratory rate) were significantly improved in both groups. In the
      dexmedetomidine-treated group, the patients had a further decreased percentage of
      failure of NIV requiring endotracheal intubation (ETI) and a more prolonged mean
      time to ETI (p=0.042, p=0.024). Furthermore, when compared with the group treated
      with midazolam, the overall duration of mechanical ventilation and the duration
      of ICU hospitalization in the group treated with dexmedetomidine were markedly
      decreased, and weaning from mechanical ventilation was easier (p=0.010, p=0.042).
      Despite the fact that more dexmedetomidine-treated patients developed bradycardia
      (18.2% vs. 0, p=0.016), no patients required an intervention or interruption of
      study drug infusion. Conversely, the incidence of respiratory infections and
      vomiting was lower in the dexmedetomidine-treated patients (p=0.026, p=0.010).
      CONCLUSION: Dexmedetomidine led to a more desired level of awaking sedation,
      shortened the duration of mechanical ventilation and the length of the ICU stay,
      and further reduced the prevalence of nosocomial infection for NIV sedation in
      patients with acute cardiogenic pulmonary edema. It appears to provide several
      advantages and safe control compared with the gamma-amino butyric acid (GABA)
      agonist midazolam.

PMID- 22975539
TI  - Demyelinating features in sensory nerve conduction in Fisher syndrome.
AB  - OBJECTIVE: A significant number of patients with Fisher syndrome (FS) exhibit
      sensory symptoms in addition to the classical triad of opthalmoplegia, ataxia and
      areflexia. Previous studies have shown the amplitudes of sensory nerve action
      potentials (SNAPs) to decrease in patients with FS, thus implying the presence of
      an axonal pathology in the sensory nerves. METHODS: We included ten consecutive
      patients with FS who were divided into the following two groups: those with
      hypesthesia (group H) and those without hypesthesia (group NS). The parameters
      obtained from nerve conduction studies (amplitudes of compound muscle action
      potentials, motor conduction velocities, amplitudes/duration of SNAPs and sensory
      conduction velocities) were retrospectively compared between the two groups. In
      addition, follow-up sensory nerve conduction studies were conducted in one
      representative patient from each group. RESULTS: Of the 10 patients with FS, four
      (40%) showed hypesthesia and eight (80%) showed distal paresthesia. The
      amplitudes of the SNAPs of both the median and sural nerves were lower in group H
      than in group NS. Moreover, the duration of the sural SNAPs was longer in group H
      than in group NS. Desynchronization of SNAPs in the acute phase was observed
      during follow-up in both patients who underwent follow-up studies. CONCLUSION:
      The prolonged duration of SNAPs in group H and the desynchronization of SNAPs in
      the two patients who underwent follow-up studies suggest the presence of a
      concomitant demyelinating process in the sensory nerves.

PMID- 22975540
TI  - Meta-analysis of drug treatment for scrub typhus in Asia.
AB  - OBJECTIVE: Scrub typhus is an important febrile disease in Asia, and antibiotics
      have been used to treat this disease. The purpose of this study was to generate
      large-scale evidence of the efficacy of different antibiotic regimens for
      treating scrub typhus using a meta-analysis. METHODS: PubMed, Elsevier
      ScienceDirect, Chinese Biomedical Literature Database (CBM), China National
      Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify
      relevant articles. The data from eligible citations were extracted by two
      reviewers. All analyses were performed using the Cochrane Collaboration Review
      Manager 4.2 and Stata 10.0 software programs. RESULTS: We conducted a meta
      analysis of 17 separate studies that evaluated the efficacy of treatment with the
      different antibiotic regimens for scrub typhus. The median time (h) to clearance
      of fever in the azithromycin-treated group was longer than that in the
      chloramphenicol-treated group (weighted mean difference [WMD] = 12.66, 95%
      confidence interval [CI]: 2.26,23.06). Adverse events were 2.95 (95%CI: 1.32,
      6.61) times more likely to occur in the azithromycin-treated group than in the
      chloramphenicol-treated group. The clearance time (days) for the main symptoms
      (including fever, headache, rash and lymphadenectasis) in the doxycycline-treated
      group was shorter than that in the chloramphenicol-treated group (WMD = -0.4,
      95%CI: -0.53, -0.26) in five trials. Adverse drug events occurred significantly
      less frequently in the azithromycin-treated group than in the doxycycline-treated
      group (relative risk [RR] = 0.47, 95%CI: 0.31,0.71). CONCLUSION: Doxycycline was
      found to act more quickly, but more adverse drug events occur when using this
      regimen compared to azithromycin and chloramphenicol.

PMID- 22975542
TI  - Hepatocellular carcinoma that relapsed 54 months after living donor liver
      transplantation.
AB  - We report the case of a 41-year-old woman with hepatocellular carcinoma (HCC).
      She received living donor liver transplantation (LDLT) from her husband for HCC
      at 36 years of age. She had few risk factors for HCC recurrence, such as elevated
      alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA) II,
      vascular invasion, and number, size of tumors. However, recurrent tumors were
      found in the graft at 54 months after LDLT. Although we examined the sex
      chromosomes of the HCC by fluorescence in situ hybridization (FISH) methods, the
      origin of the HCC was unclear. This is a very rare case of recurrent HCC
      appearing more than 4 years after LDLT in the absence of risk factors for
      recurrence.

PMID- 22975541
TI  - Solitary metastatic colon cancer showing a small depressed configuration.
AB  - We herein present a case of IIc-like metastatic lung cancer that was detected
      early. A 65-year-old man presented with diarrhea and difficulty walking.
      Colonoscopy demonstrated a depressed lesion in the descending colon. However, the
      appearance of the lesion by endoscopy with a magnifying objective was not
      compatible with early colon cancer. Therefore, we performed diagnostic endoscopic
      mucosal resection to allow for an examination of the whole lesion. A histological
      examination demonstrated lung cancer metastasis to the colon. Only 1.6% of lung
      cancers metastasize to the large intestine, and metastatic colorectal cancer is
      not usually detected at an early stage. In the present case, however, endoscopy
      and a histological examination revealed alterations in the mucosal configuration
      of the lesion, which were unusual for early colon cancer.

PMID- 22975543
TI  - Double primary cancers: intrahepatic cholangiocarcinoma with myocardial
      metastases and lung squamous cell carcinoma.
AB  - We herein present a rare case of myocardial metastases from intrahepatic
      cholangiocarcinoma. The patient was a 68-year-old man diagnosed with stage IVb
      intrahepatic cholangiocarcinoma. Growing low-density nodules at the cardiac
      interventricular septum and the left lateral wall were found on contrast enhanced
      computed tomography (CECT). He died and an autopsy was performed. Intrahepatic
      cholangiocarcinoma was found to have metastasized to the myocardium, and these
      myocardial metastases conformed to the low-density nodules detected on CECT. A
      hilar nodule in the lung was revealed to be lung squamous cell carcinoma. This
      was a rare case of intrahepatic cholangiocarcinoma with myocardial metastases and
      lung squamous cell carcinoma.

PMID- 22975544
TI  - Pulmonary arterial hypertension caused by treatment with dasatinib for chronic
      myeloid leukemia -critical alert-.
AB  - We present a case of pulmonary arterial hypertension (PAH), which is potentially
      related to treatment with dasatinib (Sprycel((r))). A 61-year-old woman, who had
      been treated with dasatinib for 27 months for chronic myeloid leukemia (CML),
      visited our hospital complaining of dyspnea. In right heart catheterization, her
      mean pulmonary arterial pressure was 35 mmHg. After other possible etiologies to
      cause PAH were excluded, the patient was diagnosed as a dasatinib-related PAH. As
      notified by U.S. Food and Drug Administration (FDA) in October 2011, we recommend
      routine cardiopulmonary evaluation before and during treatment with dasatinib in
      CML patients in terms of the adverse effects of PAH.

PMID- 22975545
TI  - Cleft-like formation of the aortic valve in an adult patient with a single
      coronary artery.
AB  - A 51-year-old woman was admitted to our hospital with heart failure due to aortic
      regurgitation. Examination showed severe aortic regurgitation mainly due to cleft
      like deformity of the right coronary cusp and single coronary artery. Aortic
      valve replacement was performed, and the deformity was seen in all aortic cusps.
      Histological study showed elongation of the leaflets by myofibrotic and fibrotic
      hyperplasia without calcification and inflammation in the aortic valve. This
      deformity likely arose from an acquired modification of a congenitally malformed
      aortic valve.

PMID- 22975546
TI  - Idiopathic accessory hemiazygos vein aneurysm with an incidental mediastinal
      mass.
AB  - We herein report the case of an idiopathic aneurysm of the accessory hemiazygos
      vein diagnosed by contrast-enhanced computed tomography (CT) and angiography. The
      patient was asymptomatic, and a posterior mediastinal mass was incidentally found
      on CT. Because endoscopic ultrasonography showed no thrombus formation in the
      aneurysm, the patient was therefore managed conservatively.

PMID- 22975547
TI  - Internal mammary arteriovenous fistula treated with transcatheter embolization.
AB  - We report an adult case of internal mammary arteriovenous fistula which was found
      to have a continuous murmur. The fistula was clearly demonstrated by multi
      detector row computed tomography and selective digital subtraction angiography,
      and was successfully occluded by transcatheter embolization.

PMID- 22975548
TI  - Aneurysm of the internal mammary artery with cystic medial degeneration.
AB  - We herein report the histopathology of a rare case of an idiopathic internal
      mammary artery aneurysm in a 61-year-old asymptomatic woman. Chest radiography
      during an annual medical check-up incidentally revealed the aneurysm, which was
      initially mistaken for a mediastinal tumor. Given that a rupture of the aneurysm
      could have been life-threatening, it was removed surgically, and found to possess
      a paper-thin arterial wall with cystic medial degeneration.

PMID- 22975549
TI  - The first Vietnamese patient with fulminant type 1 diabetes mellitus.
AB  - A 23-year-old pregnant woman had a stillbirth at 30 weeks gestation due to abrupt
      diabetic ketoacidosis. The patient had a normal HbA1c, severe hyperglycemia,
      negative islet cell autoantibodies, and very low insulin secretion capacity. The
      viral markers associated with fulminant type 1 diabetes were negative. The
      patient's human leukocyte antigen genotypes were DRB1*04:06 and DQB1*03:01/05:02,
      not common subtypes for fulminant type 1 diabetes. This is the first Vietnamese
      patient with fulminant type 1 diabetes mellitus.

PMID- 22975550
TI  - Large adrenal ganglioneuroma.
AB  - We herein report the case of a 41-year-old male patient with an incidentally
      identified large adrenal ganglioneuroma (GN). His endocrine examinations were
      normal except for one episode of elevated urinary dopamine and noradrenaline
      levels. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI)
      showed a large solid tumor with calcifications and a slightly lobular edge in the
      right adrenal gland. We performed open tumor excision and diagnosed it as adrenal
      ganglioneuroma. Adrenal GN is a rare benign tumor, and its hormonal activity and
      imaging characteristics are occasionally very similar to those of other adrenal
      tumors. Therefore, it needs careful evaluation by endocrine examinations and
      multiple imaging procedures to rule out other types of tumors.

PMID- 22975551
TI  - Rhabdomyolysis in acute primary adrenal insufficiency complicated by severe
      hyponatraemia.
AB  - Patients with acute adrenal insufficiency may have musculoskeletal symptoms
      including flexion contractures, myopathy and hyperkalaemic neuromyopathy.
      However, the association between rhabdomyolysis and acute adrenal insufficiency
      is extremely rare and has only been reported infrequently in the literature.
      Hyponatraemia is often present in association with acute adrenal insufficiency
      complicated by rhabdomyolysis. We herein report the case of a patient with acute
      primary adrenal insufficiency and severe hyponatraemia complicated by
      rhabdomyolysis and acute kidney injury.

PMID- 22975552
TI  - Fibroblast growth factor 23-related osteomalacia caused by the prolonged
      administration of saccharated ferric oxide.
AB  - A 44-year-old woman with iron deficiency anemia was on a continuous course of
      intravenous saccharated ferric oxide (SFO). She came to our hospital because of
      right hip joint pain. She was found to have hypophosphatemia caused by impaired
      phosphorus resorption and her fibroblast growth factor 23 (FGF-23) levels were
      elevated. Therefore, she was diagnosed with FGF-23-related osteomalacia due to
      SFO administration. Discontinuation of the SFO treatment rapidly improved the
      impaired phosphorus resorption and also normalized the blood levels of phosphorus
      and FGF-23. During the treatment with SFO, it is important to regularly measure
      the blood levels of phosphorus in order to prevent the occurrence of
      osteomalacia.

PMID- 22975553
TI  - Thyroid storm with multiple organ failure, disseminated intravascular
      coagulation, and stroke with a normal serum FT3 level.
AB  - Thyroid storm is a rare disorder with a sudden onset, rapid progression and high
      mortality. We experienced a case of thyroid storm which had a devastating course,
      including multiple organ failure (MOF), severe hypoglycemia, disseminated
      intravascular coagulation (DIC), and stroke. It was difficult to make a diagnosis
      of thyroid storm in the present patient, because she did not have a history of
      thyroid disease and her serum FT3 level was normal. Clinicians should be aware
      that thyroid storm can occur even when there is an almost normal level of thyroid
      hormones, and that intensive anticoagulation is required for patients with atrial
      fibrillation to prevent stroke after thyroid storm.

PMID- 22975554
TI  - IgG4-associated tubulointerstitial nephritis: two case reports and a literature
      review.
AB  - IgG4-related systemic disease (IgG4-RSD) is an autoimmune disease that includes a
      wide variety of lesions. IgG4-RSD is characterized by high levels of serum IgG4,
      abundant levels of IgG4-positive plasma cells and T-lymphocyte infiltration in
      various organs. Tubulointerstitial nephritis (TIN) is a major finding when the
      kidneys are involved and is effectively treated with corticosteroid therapy. We
      herein describe two cases of IgG4-related TIN. Such cases have rarely been
      reported in China.

PMID- 22975555
TI  - Myeloperoxidase anti-cytoplasmic antibody related crescentic glomerulonephritis
      in a patient with IgG3lambda monoclonal immunoglobulin deposition disease with
      membranous features.
AB  - A 68-year-old woman showed rapidly progressive glomerulonephritis based on the
      fact that she had 1+ proteinuria (1.1 g/day), a 3+ occult blood reaction, blood
      urea nitrogen of 32.4 mg/dL, serum creatinine of 2.96 mg/dL, and myeloperoxidase
      (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA) at 52 ELISA Unit (normal
      range: below 10). A renal biopsy demonstrated a bubbling appearance associated
      with cellular crescent formation with segmental necrosis. Immunofluorescence
      studies showed granular IgG3lambda deposition along the basement membrane and in
      the mesangial area. This is the first English-language case report describing MPO
      ANCA positive crescentic glomerulonephritis in a patient demonstrating monoclonal
      immunoglobulin deposition disease with mainly membranous features.

PMID- 22975556
TI  - Carboplatin plus paclitaxel in the successful treatment of advanced inflammatory
      myofibroblastic tumor.
AB  - A 26-year-old man with unresectable inflammatory myofibroblastic tumor (IMT)
      presented with multiple metastases in the thoracic vertebra and lymph nodes as
      detected by positron emission tomography (PET) received chemotherapy with
      carboplatin plus paclitaxel. After three cycles of chemotherapy, fluorine-18
      fluorodeoxyglucose (FDG)-PET/CT revealed tumor regression and significant
      reduction of FDG uptake in all lesions. The patient received six cycles of
      chemotherapy without any severe adverse event, and there was no sign of disease
      progression for seven months. This regimen is well tolerated and may be
      considered the treatment of choice for unresectable IMT.

PMID- 22975557
TI  - Chyloptysis after ligation of the thoracic duct.
AB  - Chyloptysis is a very rare clinical finding. We describe a 44-year-old man who
      presented with cough and milky-white sputum. Fiberoptic bronchoscopy revealed
      white sputum, which originated from the right B(6) bronchus. The finding of
      elevated triglyceride levels in his sputum led to the diagnosis of chyloptysis.
      He had a surgical history of ligation of the thoracic duct for idiopathic
      chylopericarditis 7 years-previously. He also suffered from postoperative
      bilateral empyema. Since then, his pleural cavity has been adhered bilaterally.
      It is thought that his abnormal postoperative lymphatic flow caused the
      chyloptysis.

PMID- 22975558
TI  - Synchronous gastrointestinal stromal tumor and primary lung adenocarcinoma.
AB  - Although rare, gastrointestinal stromal tumors (GIST) are the most common
      mesenchymal tumors of the gastrointestinal tract. The asynchronous occurrence of
      other malignancies in patients with GIST during the clinical course is relatively
      common. However, the synchronous coexistence of GIST and lung cancer has only
      rarely been reported. We experienced a case of coincidental primary lung
      adenocarcinoma and intestinal GIST. The present case is not only of interest due
      to the rare coincidence of GIST and lung cancer, but also because there was an
      epidermal growth factor receptor gene mutation in the lung cancer and a c-kit
      mutation in the GIST.

PMID- 22975559
TI  - Azacitidine-induced pneumonitis in a patient with myelodysplastic syndrome: first
      case report in Japan.
AB  - A 74-year-old Japanese man with myelodysplastic syndrome (MDS) received
      chemotherapy with azacitidine. From the second day after starting the
      administration, he complained of fever, cough and shortness of breath. Chest
      roentgenography and computed tomography showed consolidations and ground-glass
      opacities. His symptoms grew from worse to life-threatening. We diagnosed him
      with azacitidine-induced pneumonitis and began administering corticosteroids.
      Thereafter, his symptoms and radiographic abnormalities improved. Azacitidine is
      a hypomethylating agent that improves the survival of MDS patients. Although this
      drug is commonly well tolerated and rarely causes severe lung injury, it is
      important to consider the potentially serious adverse effects of azacitidine
      induced pneumonitis.

PMID- 22975560
TI  - Hepatic portal venous gas associated with severe graft-versus-host disease of the
      gastrointestinal tract.
AB  - We report a 67-year-old woman who was diagnosed with hepatic portal venous gas
      associated with severe graft-versus-host disease (GVHD) of the gastrointestinal
      tract. The patient received allogenic peripheral blood stem cell transplantation
      from a haploidentical son against Philadelphia chromosome-positive acute
      lymphocytic leukemia. The patient developed grade 3 intestinal GVHD on day 90
      from the transplantation. On day 149, she presented septic shock and computed
      tomography (CT) scan revealed hepatic portal venous gas (HPVG); an ileocecal
      resection was performed immediately. The damage of gastrointestinal mucosa by
      GVHD resulted in the invasion of gas-producing bacteria. Although HPVG-associated
      gastrointestinal GVHD is extremely rare, we should pay special attention to this
      pathogenesis.

PMID- 22975561
TI  - Anti-Hu-associated paraneoplastic encephalomyelitis with esophageal small cell
      carcinoma.
AB  - A 63-year-old woman had anti-Hu-associated paraneoplastic encephalomyelitis (anti
      Hu syndrome) caused by esophageal small cell carcinoma (SCC). The patient
      developed bilateral limbic encephalitis, followed by myelitis, brain stem
      encephalitis, and autonomic failure. Extensive examination demonstrated SCC of
      the abdominal lymph nodes that was retrospectively diagnosed as metastasis of
      esophageal SCC on autopsy. The neuropathological findings were characterized by
      widespread neuronal loss and gliosis in the central nervous system, as well as
      patchy loss of myelin and axons in the spinal nerve roots with perivascular
      lymphocytic infiltration. This is the first detailed clinical and
      neuropathological report of anti-Hu syndrome caused by esophageal SCC.

PMID- 22975562
TI  - Opsoclonus-myoclonus syndrome following influenza a infection.
AB  - A 60-year-old woman developed opsoclonus-myoclonus syndrome (OMS) a week after
      being diagnosed with influenza A infection by a rapid antigen test. She had no
      loss of consciousness. Opsoclonus, myoclonus, and truncal ataxia were noted. Two
      weeks after treatment with intravenous immunoglobulin and corticosteroids, her
      opsoclonus, myoclonus, and truncal ataxia disappeared. No malignant tumors were
      detected during the 3-year follow-up period. There has been no previous report of
      postinfectious OMS following confirmed influenza A infection. OMS without a loss
      of consciousness has been reported to be statistically less common in cases of
      non-paraneoplastic OMS. This finding was consistent with the present patient's
      clinical manifestations.

PMID- 22975563
TI  - Sudden deafness and facial diplegia in Guillain-Barre Syndrome: radiological
      depiction of facial and acoustic nerve lesions.
AB  - We herein report a 26-year-old man with Guillain-Barre Syndrome (GBS) coexisting
      facial nerve palsy (FP) and deafness. He developed deafness, facial weakness, and
      limb weakness and numbness. Neurological examination showed facial diplegia,
      bilateral hypoacusia, areflexia and sensorimotor deficits in the distal limbs.
      The nerve conduction study findings supported the diagnosis of the demyelinating
      polyneuropathy. An audiogram revealed sensorineural hearing loss of 40-50 dB.
      Auditory brainstem responses disclosed no elicitation of waves I to IV on both
      sides. Magnetic resonance imaging depicted abnormal enhancement in bilateral
      facial and acoustic nerves. Physicians should pay more attention to auditory
      dysfunction in GBS patients with FP.

PMID- 22975565
TI  - Acute combined central and peripheral demyelination showing anti-aquaporin 4
      antibody positivity.
AB  - Neuromyelitis optica spectrum disorder (NMOSD) is characterized by optic neuritis
      or transverse myelitis with anti-aquaporin 4 (AQP4) antibodies (1). We herein
      present the case of a patient with NMOSD who also was affected with peripheral
      neuropathy. A 58-year-old woman developed gait disturbance and sensory impairment
      in the lower limbs. She exhibited longitudinally extensive transverse myelitis
      with anti-AQP4 antibodies. Nerve conduction studies showed demyelinating changes.
      Laboratory findings showed hepatitis-C virus (HCV) infection. Her peripheral
      neuropathy improved after immunotherapy. There have been no previous reports of
      NMO or NMOSD associated with neuropathy. The HCV infection or undetermined
      humoral factors other than the anti-AQP4 antibodies may have caused her
      peripheral neuropathy.

PMID- 22975566
TI  - Postanoxic akinesia with bilateral pallidal lesions: a PET study.
AB  - A 70-year-old woman developed marked akinesia after an anoxic event related to
      bronchiectasia. Magnetic resonance imaging studies revealed lesions in the
      bilateral globus pallidus and, to a lesser extent, in the putamen. Positron
      emission tomography studies with (18)F-6-fluoro-L-dopa and (11)C-N
      methylspiperone showed a decreased pre- and post-synaptic uptake in the striatum.
      Consistent with previous reports, the present case demonstrated the basal
      ganglia, particularly the globus pallidus, to be selectively susceptible to
      anoxic insults. Furthermore, a PET study indicated a disrupted presynaptic
      integrity of the dopaminergic terminals and decreased dopamine D(2) receptor
      binding, which together appear to underlie the pathophysiology of post-anoxic
      akinesia, at least in the present case.

PMID- 22975564
TI  - Varicella-zoster virus infection and nummular headache: a possible association
      with epicranial neuralgia.
AB  - A nummular headache (NH) is a type of primary headache that results from cranial
      neuralgia without a known cause. We herein report the case of a woman who
      suffered two episodes of focal headache in the left parietal area with identical
      characteristics that were compatible with NH. During the recovery phase of the
      second NH episode, the pain resurged with shingles coinciding with the painful
      area. The patient's NH subsided in parallel with resolution of the shingles.
      These findings support a diagnosis of peripheral neuralgia with NH. Latent virus
      infections, such as Varicella-zoster virus, that frequently cause distal nerve
      damage in patients with zoster sine herpete may be associated with epicranial
      neuralgia and NH.

PMID- 22975567
TI  - Transient increase in epileptiform discharges after the introduction of nasal
      continuous positive airway pressure in a patient with obstructive sleep apnea and
      epilepsy.
AB  - In patients with obstructive sleep apnea (OSA) and epilepsy, the frequency of
      generalized spike and wave complexes (GSWCs) usually decreases after the
      initiation of nasal continuous positive airway pressure (nCPAP) therapy. However,
      we herein report a patient who had a transient increase in GSWCs following nCPAP
      treatment. A woman with epilepsy underwent polysomnography, who showed severe OSA
      and 30 GSWCs during the sleep study. Polysomnography at the introduction nCPAP
      showed that the GSWCs increased to 94 times during the monitoring period, despite
      improvement of her OSA. Polysomnography was again performed four months later,
      and the GSWCs had decreased to 23 times. Physicians should therefore be cautious
      regarding a possible increase in epileptiform discharges and seizures immediately
      after the introduction of nCPAP.

PMID- 22975568
TI  - Churg-Strauss syndrome concomitant with chronic symmetrical dacryoadenitis
      suggesting Mikulicz's disease.
AB  - A case of Churg-Strauss syndrome complicated by chronic symmetrical
      dacryoadenitis suggestive of Mikulicz's disease is herein presented. A 72-year
      old Japanese man, who had been previously diagnosed with asthma, presented with
      weakness of the left leg and purpura on the lower extremities. A neurological
      examination showed multiple mononeuropathies and a laboratory examination
      revealed elevated eosinophil counts, IgE levels and the presence of
      Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCAs). Churg-Strauss
      syndrome was diagnosed, although the patient also exhibited bilateral swelling of
      the lachrymal glands. Furthermore, elevated serum IgG4 levels, an infiltration of
      a relatively large number of IgG4-positive plasmacytes in the nasal mucosa and
      hypocomplementemia were also observed. These findings were consistent with a
      diagnosis of Mikulicz's disease (MD). Oral prednisolone (30 mg) was administered
      and the swelling of the lachrymal glands resolved. Churg-Strauss syndrome may be
      accompanied by Mikulicz's disease (an IgG4-related disease), and common
      pathogeneses between Churg-Strauss syndrome and IgG4-related disease may exist.

PMID- 22975569
TI  - Necrotizing pneumonia in the community.
AB  - A 62-year-old man presented with general fatigue. He was diagnosed with septic
      shock and severe pneumonia. The sputum at admission yielded methicillin-sensitive
      Staphylococcus aureus (MSSA) strain and methicillin-resistant S. aureus (MRSA)
      strain. Despite antibiotic treatment, he did not improve. A chest computed
      tomography (CT) revealed multilobar cavity lesions. Only MRSA strain was
      confirmed at that time. We diagnosed him with necrotizing pneumonia. Despite
      treatment with vancomycin, his pneumonia worsened and he died. At autopsy, many
      gram-positive cocci were observed in the lungs. The clinical presentation of our
      patient was different from typical CA-MRSA-mediated necrotizing pneumonia.

PMID- 22975570
TI  - Drug-induced acute interstitial nephritis mimicking acute tubular necrosis after
      initiation of tenofovir-containing antiretroviral therapy in patient with HIV-1
      infection.
AB  - We describe a case of 68-year-old Japanese man with HIV-1 infection who developed
      acute kidney injury with prominent tubular dysfunction immediately after starting
      tenofovir-containing antiretroviral therapy. Antiretroviral therapy was
      discontinued in two weeks but renal function, as well as tubular function, did
      not shown full recovery even at a 3-year follow-up examination. Acute tubular
      necrosis, a rare but well-known side effect of tenofovir, was suspected, but
      kidney biopsy confirmed interstitial nephritis. It is important to distinguish
      drug-induced interstitial nephritis from acute tubular necrosis, because early
      steroid administration can improve renal dysfunction caused by acute interstitial
      nephritis.

PMID- 22975571
TI  - Successful treatment of fulminant community-acquired Pseudomonas aeruginosa
      necrotizing pneumonia in a previously healthy young man.
AB  - This report presents a case of fulminant community-acquired Pseudomonas
      aeruginosa necrotizing pneumonia in a previously healthy young man, including an
      analysis of the virulence of the P.aeruginosa isolated from the patient. The
      patient was successfully treated with intensive care and antibiotic treatment.
      This study analyzed the pathogenicity of the isolated strain both in vivo (using
      a mouse pneumonia model) and in vitro (using biofilm production), but could not
      explain how an otherwise healthy young man developed such severe community
      acquired P.aeruginosa pneumonia. Although rare in community-acquired pneumonia,
      P.aeruginosa infection should be considered in patients with severe rapidly
      progressive pneumonia.

PMID- 22975572
TI  - Cutaneous metastases of rectal mucinous adenocarcinoma mimicking granuloma
      inguinale.
AB  - A 46-year-old man complained of ulcerovegetative lesions in the anogenital
      region, which he had noted one month prior to presentation. The patient had a
      history of travel to African countries. Therefore, the ulcerovegetative lesions
      of the patient were suspected to be granuloma inguinale (GI). Calymmatobacterium
      granulomatis was not observed in the direct examination of scrapings collected
      from the base of the ulcerovegetative lesion. Instead, a histological examination
      revealed cutaneous metastasis of mucinous adenocarcinoma of the rectum.
      Therefore, a diagnosis of GI was eliminated. As the patient did not report his
      history of rectal cancer and had travelled to African countries, we had primarily
      focused on the diagnosis of GI.

PMID- 22975573
TI  - A good outcome of a case with eosinophilic myocarditis.

PMID- 22975575
TI  - Malignant lung melanoma mimicking mucoid impaction on imaging.

PMID- 22975574
TI  - Acute renal infarction: an atypical presentation of Leriche syndrome.

PMID- 22975576
TI  - Hyaline vascular type Castleman's disease of the mesentery.

PMID- 22975578
TI  - A dog bite injury after the Fukushima nuclear accident.

PMID- 22975577
TI  - Leukocytoclastic vasculitis after steroid injection.

PMID- 22975579
TI  - Henoch-Schonlein purpura with intussusception in an adult.
AB  - Often seen in childhood, Henoch-Schonlein purpura (HSP) is a self-limiting
      illness, in which complications involving intussusception are rarely found in
      adults. This study reported a case of HSP initially presented as intussusception
      in a 60-year-old man. Gastrointestinal manifestations before the onset of rash
      may prevent an accurate diagnosis and appropriate management. Primary care
      physicians should be alert for this association between intussusception and HSP,
      especially in adult patients.

PMID- 22975580
TI  - Incidence of musculoskeletal and neoplastic diseases in patients on statin
      therapy: results of a retrospective cohort analysis.
AB  - BACKGROUND: Because of their beneficial cardiovascular effects, several studies
      have recently advocated starting statins at a young age for primary prevention.
      However, some reports suggest that statin therapy may be associated with an
      increased incidence of musculoskeletal and neoplastic diseases. This study was
      conducted to investigate the incidence of various musculoskeletal and neoplastic
      diseases in statin users and nonusers. METHODS: A retrospective cohort study of
      patients in the San Antonio Military Multi-Service Market during the period from
      October 1, 2003, to March 5, 2010, was conducted. The International
      Classification of Diseases, 9th edition, diagnosis codes between 2 cohort groups
      statin users and nonusers-were compared. Statin users were those patients with at
      least one 3-month prescription for a statin in the fiscal year 2004. Nonusers
      were those patients who received a prescription-but not a statin-during the
      period of the study. Both groups were assessed for the development of
      musculoskeletal and neoplastic diseases in the following 4-year period (October
      1, 2004, to September 30, 2009). RESULTS: A total of 92,360 patients were
      identified: 12,980 statin users and 45,997 nonusers. After adjusting for age, sex
      and Charlson comorbidity index, statin users had significantly higher rates of
      osteoarthritis and arthropathy (odds ratio: 1.26; 95% confidence interval: 1.19
      1.33), and dorsopathies, rheumatism and chondropathies (odds ratio: 1.20; 95%
      confidence interval: 1.12-1.27). CONCLUSIONS: In this retrospective analysis,
      statin use was associated with an increased incidence of musculoskeletal
      diseases, including arthropathy. Further studies are needed to provide physicians
      and their patients with adequate information regarding statin therapy,
      particularly if recommended for primary prevention in younger populations.

PMID- 22975581
TI  - Imatinib increases apoptosis index through modulation of survivin subcellular
      localization in the blast phase of CML cells.
AB  - Using MTT, Annexin V/flow cytometry, immunocytochemistry, subcellular
      fractionation, and Western blotting assays we analyzed the effect of imatinib in
      two blast phase of chronic myeloid leukemia (CML) cell lines: K562 P-glycoprotein
      (Pgp)-negative, and Lucena, Pgp-positive. In K562 cell line, the high apoptosis
      index induced by imatinib was associated with the survivin predominantly in the
      nucleus. In the Lucena cell line, the low apoptosis index induced by imatinib was
      associated with a cytoplasmatic survivin localization. Pgp and survivin might be
      subject to the same molecular regulation, and therefore represent a therapeutic
      target in the blast phase of CML.

PMID- 22975582
TI  - RNA interference-mediated secretory clusterin gene silencing inhibits
      proliferation and promotes apoptosis of human non-small cell lung cancer cells.
AB  - BACKGROUND/AIMS: Non-small cell lung cancer (NSCLC) constitutes around 85% of
      lung cancer cases and is frequently beyond surgical intervention. METHODOLOGY:
      Secretory clusterin (sCLU) is found in diverse types of human cancers and is
      unregulated in a variety of cell lines in response to stress, and enhances cancer
      cell survival. However, the roles of sCLU in NSCLC are still to be elucidated.
      RESULTS: Here we show that RNA interference (RNAi)-mediated sCLU gene silencing
      with short interference RNA (siRNA) strongly decreased the sCLU mRNA and protein
      levels, as well as suppressed cell proliferation and induced cell apoptosis. In
      addition, sCLU siRNA also blocked the PI3K/AKT signaling pathway, and decreased
      the AKT phosphorylation level, but no change was found in total AKT level. More
      importantly, PI3K/AKT signaling pathway inhibitor, LY294002, also reduced tumor
      cell proliferation, which is similar to the result with or without sCLU siRNA
      treatment. CONCLUSIONS: These results suggest that sCLU plays a positive role in
      NSCLC cell proliferation, which may be mediated by the PI3K/AKT signaling
      pathway. Our work in this study demonstrates RNAi-mediated sCLU gene silencing
      may provide a novel therapeutic strategy in the treatment of NSCLC.

PMID- 22975583
TI  - Elevation of the AST to ALT ratio in association with the severity of esophageal
      varices in patients with HCV-related compensated liver cirrhosis.
AB  - BACKGROUND/AIMS: The development of esophageal varices depends on the progression
      of liver fibrosis. However, it has not yet been sufficiently clarified whether
      biomarkers of liver fibrosis can be used to predict the incidence of varices in
      cirrhotic patients with a well-maintained liver function (Child-Pugh class A).
      METHODOLOGY: Three established markers of liver fibrosis, including AST-to-ALT
      ratios (AAR), FIB-4 and AST-to-platelet ratio indices (APRI), were analyzed in
      HCV-positive cirrhotic patients with Child-Pugh class A status, and the
      relationships between these markers and the risk of variceal bleeding were
      investigated. RESULTS: The values of AAR and FIB-4 in the patient with varices
      with a high risk of hemorrhage were significantly higher than those in the
      patients without high-risk varices, whereas the value of APRI was not found to be
      related to the risk of variceal bleeding. Of all the parameters examined, the
      values of AAR were the most significantly different between the two (with or
      without high-risk varices) groups. In addition, the values of AAR increased in
      line with variceal severity. CONCLUSIONS: The value of AAR is related to the
      severity and risk of variceal bleeding in patients with HCV-related compensated
      cirrhosis.

PMID- 22975584
TI  - Outcomes of endoscopic submucosal dissection for early gastric cancer and factors
      associated with incomplete resection.
AB  - BACKGROUND/AIMS: The introduction of endoscopic submucosal dissection for the
      treatment of early gastric cancer has enabled en bloc resection of lesions that
      cannot be treated with conventional endoscopic mucosal resection. Despite
      expansion of indications for endoscopic treatment, a considerable number of
      patients still require additional treatment. The objective of this study was to
      summarize the outcomes of endoscopic submucosal dissection performed on patients
      with early gastric cancer and to identify factors associated with incomplete
      resection and non-curative resection. METHODOLOGY: This study examined 605
      lesions in 533 patients with early gastric cancer who underwent endoscopic
      submucosal dissection. Evaluation of treatment outcome was based on the rates of
      complete resection and curative resection. Factors associated with incomplete
      resection and non-curative resection were retrospectively identified. RESULTS: Of
      the 605 lesions, 562 (92.9%) and 510 (84.3%) were diagnosed as complete resection
      and curative resection, respectively. Factors identified as associated with
      incomplete resection were tumor size >=30 mm, location in the U region,
      undifferentiated carcinoma, sm2 invasion and ulceration. Factors identified as
      associated with non-curative resection were tumor size >=30 mm, location in the U
      region and ulceration. CONCLUSIONS: Incomplete and non-curative resection appears
      to be associated with preoperative diagnosis of lesions and technical difficulty.

PMID- 22975585
TI  - Evidence for premature lipid raft aging in APP/PS1 double-transgenic mice, a
      model of familial Alzheimer disease.
AB  - Altered lipid raft homeostasis has been considered to contribute to cellular
      deregulation, leading to neuronal loss in Alzheimer disease. Alterations in these
      microdomains affect amyloid precursor protein (APP) processing, resulting in
      neurotoxic conditions, but modifications of the molecular structure of lipid
      rafts in Alzheimer disease model mice have not been characterized. Using a
      lipidomic approach, we investigated frontal cortex lipid rafts inwild-type mice
      and in double-transgenic APP/presenilin 1 (PS1) mice. Lipid rafts in wild-type
      mice undergo age-dependent modifications, that is, decreased cholesterol and
      sterol esters levels, augmented sphingomyelin and saturated fatty acid content,
      and increased phospholipids/cholesterol ratio. These age-dependent changes were
      more dramatic and occurred earlier in APP/PS1 mice; other lipid classes (e.g.
      sulfatides) and essential long-chain polyunsaturated fatty acids (including
      docosahexaenoic and arachidonic acids) were also affected. Steady state
      anisotropy measurements demonstrated that APP/PS1 animals exhibit more viscous
      (membrane-ordered) lipid rafts and that this is mainly attributable to reduced
      unsaturation of phospholipids and increased sphingomyelin levels rather than to
      changes in cholesterol. In summary, we demonstrate that aging is accompanied by
      alteration of the physicochemical structure of lipid raft microdomains. This
      "lipid raft aging," a metaphenomenon, is considerably exacerbated by the induced
      amyloid burden in APP/PS1 genotype.

PMID- 22975586
TI  - Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human
      muscle: role of calpain-3 and nuclear factor-kappaB signaling.
AB  - Ullrich congenital muscular dystrophy (UCMD) is a common form of muscular
      dystrophy associated with defects in collagen VI. It is characterized by loss of
      individual muscle fibers and muscle mass and proliferation of connective and
      adipose tissues. We sought to investigate the mechanisms by which collagen VI
      regulates muscle cell survival, size, and regeneration and, in particular, the
      potential role of the ubiquitin-proteasome and calpain-proteolytic systems. We
      studied muscle biopsies of UCMD (n = 6), other myopathy (n = 12), and control
      patients (n = 10) and found reduced expression of atrogin-1, MURF1, and calpain-3
      mRNAs in UCMD cases. Downregulation of calpain-3 was associated with changes in
      the nuclear immunolocalization of nuclear factor-kappaB. We also observed
      increased expression versus controls of regeneration markers at the protein and
      RNA levels. Satellite cell numbers did not differ in collagen VI-deficient muscle
      versus normal nonregenerating muscle, indicating that collagen VI does not play a
      key role in the maintenance of the satellite cell pool. Our results indicate that
      alterations in calpain-3 and nuclear factor-kappaB signaling pathways may
      contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are
      not likely to play a major role.

PMID- 22975587
TI  - Monkeys show recognition without priming in a classification task.
AB  - Humans show visual perceptual priming by identifying degraded images faster and
      more accurately if they have seen the original images, while simultaneously
      failing to recognize the same images. Such priming is commonly thought, with
      little evidence, to be widely distributed phylogenetically. Following Brodbeck
      (1997), we trained rhesus monkeys (Macaca mulatta) to categorize photographs
      according to content (e.g., birds, fish, flowers, people). In probe trials, we
      tested whether monkeys were faster or more accurate at categorizing degraded
      versions of previously seen images (primed) than degraded versions of novel
      images (unprimed). Monkeys categorized reliably, but showed no benefit from
      having previously seen the images. This finding was robust across manipulations
      of image quality (color, grayscale, line drawings), type of image degradation
      (occlusion, blurring), levels of processing, and number of repetitions of the
      prime. By contrast, in probe matching-to-sample trials, monkeys recognized the
      primes, demonstrating that they remembered the primes and could discriminate them
      from other images in the same category under the conditions used to test for
      priming. Two experiments that replicated Brodbeck's (1997) procedures also
      produced no evidence of priming. This inability to find priming in monkeys under
      perceptual conditions sufficient for recognition presents a puzzle.

PMID- 22975588
TI  - Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene
      from the marine derived Streptomyces sp.
AB  - In continuing research for compounds with immunosuppressive activity, Lawsonone
      (1), a novel Lawsonyl derivative isolated from marine-derived bacteria
      Streptomyces sp. was evaluated for its potent immunosuppressive activity on
      immune system. The effect of Lawsonone (1) was elucidated on the immune cells
      (splenocytes and macrophages) collected from BALB/c mice. Study was carried out
      to find the effect of Lawsonone (1) on Con-A and LPS stimulated splenocyte
      proliferation, LPS-induced NO, IL-1beta, IL-6 and TNF-alpha production in
      macrophages. Furthermore, the effect of Lawsonone (1) on T-cell subsets (CD4 and
      CD8) and total B-cell (CD19) population was analyzed by flow cytometry. The
      results obtained in the present study showed that Lawsonone (1) inhibited the
      proliferation of both T and B splenocytes. It inhibited the nitric oxide (NO) and
      pro-inflammatory cytokine (IL-1beta, IL-6 and TNF-alpha) production in LPS
      stimulated macrophages in a dose-dependent manner. Moreover, flow cytometric
      analysis indicated the prominent inhibition of CD4, CD8 and CD19 cell populations
      in the spleen of mice treated with the variable doses of Lawsonone (1), with the
      maximum inhibition at the lowest dose (0.1MUM). Taken together, the present
      results suggest that Lawsonone (1) may act as a potent molecule for
      immunosuppression and anti-inflammation, supporting its immunopharmacologic
      application to modify the immune system.

PMID- 22975589
TI  - Gynecologic rarities: a case of periclitoral abscess and review of the
      literature.
AB  - Periclitoral abscess is a rare entity, with publications limited to case reports.
      We present here a case of periclitoral abscess in a 17 year old patient, which
      was treated with incision and drainage. We also review all the similar cases that
      have been reported in the English literature until now.

PMID- 22975590
TI  - Cross-sectional associations between the five factor personality traits and
      leisure-time sitting-time: the effect of general self-efficacy.
AB  - BACKGROUND: Leisure-time sitting-time (LTST) is seen as a possible independent
      risk-factor for physical and mental health, but research on psychological
      determinants is sparse. Associations between sitting-time and the personality
      dimensions of neuroticism, extroversion, openness, agreeableness, and
      conscientiousness, and the role of general self-efficacy (GSE) were investigated.
      METHODS: A population-based, cross-sectional study was conducted at the Research
      Centre for Prevention and Health, Denmark, in 2006-08. Men and women (N = 3471)
      aged 18 to 69, were randomly sampled in the suburbs of Copenhagen. The NEO Five
      Factor Inventory, the General Self-Efficacy-Scale, and the Physical Activity
      Scale 2 were used. RESULTS: Negative associations were found between LTST and
      extroversion, conscientiousness, and openness, while neuroticism showed a
      positive association (R2 = .13). The associations with agreeableness became
      significantly positive, when GSE was included. All 5 associations were mediated
      by GSE, with mediation proportions between 23%-60%; but with modest effect sizes.
      CONCLUSIONS: These cross-sectional results indicate that personality traits and
      GSE could be considered as associates of LTST; but future longitudinal data are
      necessary to make causal statements and rule out alternative models fitting data.

PMID- 22975591
TI  - MicroRNAs involved in regulating epithelial-mesenchymal transition and cancer
      stem cells as molecular targets for cancer therapeutics.
AB  - One of the major challenges in cancer gene therapy is the identification of
      functionally relevant tumor-specific genes as the therapeutic targets. MicroRNAs
      (miRNAs) are a class of small, 22-25 nucleotides, endogenously expressed
      noncoding RNA. miRNAs are important genetic regulators: one miRNA can possibly
      target multiple genes and they can function as tumor promoters (oncogenic miRNAs,
      oncomirs) or tumor suppressors (anti-oncomirs). Therefore, the identification of
      misregulated miRNAs in cellular signaling pathways related to oncogenesis can
      have profound implications for cancer therapy. The epithelial-mesenchymal
      transition (EMT) converts epithelial cells into mesenchymal cells, a normal
      embryological process that frequently get activated during cancer invasion and
      metastasis. Recent evidence also supports the presence of a small subset of self
      renewing, stem-like cells within the tumor mass that possess the capacity to seed
      new tumors and they have been termed 'cancer stem cells (CSC)'. Conceivably,
      these CSCs could provide a resource for cells that cause therapy resistance.
      Although the cell origin of CSCs remains to be fully elucidated, a growing body
      of evidence has demonstrated that the biology of EMT and CSCs is tightly linked
      with the sequences and compositions of miRNA molecules. Therefore, targeting
      miRNAs involved in EMT and CSCs regulation can provide novel miRNA-based
      therapeutic strategies in oncology.

PMID- 22975592
TI  - Readability and Missing Data Rates in CAHPS 2.0 Medicare Survey in African
      American and White Medicare Respondents.
AB  - PURPOSE: Examine associations between readability of survey items and missing
      data rates in a sample of White and African American (AA) Medicare enrollees in
      managed care plans.  METHODS: Consumer Assessment of Healthcare Provider and
      Systems (CAHPS((r))) 2.0 health plan survey data collected from 139,284
      respondents (127,524, Whites and 11,760, AAs) in 321 health plans. Product-moment
      correlations were computed between Flesch-Kincaid (F-K) readability estimates and
      the CAHPS((r)) item missing data rates.  RESULTS: F-K reading levels for items
      ranged from 4.8 to 17.7 with a mean of 8.9 across items. Missing data rates
      ranged from 1 to 10%, with AAs having significantly higher missing data rates.
      Correlations between missing data rates and item-level readability were
      statistically significant for Whites (r = 0.33, p = 0.0515) and AAs (r = 0.37, p
      =0.0284).  CONCLUSIONS: The significant associations between missing data rates
      and item-level readability estimates indicate that the completion of survey items
      varies by their readability. Enhancing the readability of survey items can
      improve the inclusion of survey data collected from different respondents.

PMID- 22975593
TI  - Oncoepigenomics: making histone lysine methylation count.
AB  - Increasing studies show that methylation of histone lysine residues is implicated
      in the development and progression of varying disease states such as
      schizophrenia, diabetes, and multiple human cancers. Targeting the specific
      enzymes responsible for these processes has fueled global investigation into the
      understanding and correction of epigenetic pathology. This review aims to
      assemble a timely account of the current progress against chromatin-modifying
      histone lysine methyltransferases (KMTs) and demethylases (KDMs) to inform
      ongoing and future efforts into this promising field. In particular, we report on
      their role in tumor growth and progression and the development of small molecules
      that modulate these enzymes.

PMID- 22975594
TI  - [Not Available].

PMID- 22975595
TI  - Direct action of triiodothyronine on gene expression in the neonatal brain and
      cerebellum.
AB  - Thyroid hormones play a major role in the development and function of several
      organs, especially the brain. The actions of thyroid hormones are exerted through
      the interaction of T3 with nuclear receptors and regulation of gene expression.
      The present study analyzed the effects of hypothyroidism and T3 administration on
      gene expression in the rat brain and cerebellum during the postnatal period. To
      obtain hypothyroid pups, antithyroid drugs were administered to pregnant rats
      from gestational day 9, and after delivery. T3 was administered to the pups, at
      single daily doses of 5ng/g body weight from postnatal day 11 to 15. The pups
      were sacrificed 24hours after the last injection. Hypothyroid neonates showed
      increased cholesterol levels and decreased expression of D1 in liver and of Serca
      2 in heart, which were normalized with T3 treatment. In the brain, there was
      decreased expression of Ngrn and Rasd2 in the striatum and of the genes encoding
      sinatotagmin12 (Syt12), hairless (Hr), neurotrofina3 (Nt3) and
      RevErbAalpha(Nrd1d) in the cerebellum, which were also normalized by T3
      treatment. These results demonstrate that during the postnatal period, T3 reaches
      the brain and directly influences gene expression in this organ. In parallel, we
      studied the possible actions of a T3 analog, Kb430, which in vitro binds
      preferentially to thyroid receptor alpha (TRalpha). This compound had no effect
      on any of the parameters studied. To investigate whether the lack of activity of
      this compound was due to rapid metabolism, we compared its activity with that of
      T3 in T3 receptor transactivation assays using the reporter gene chloramphenicol
      acetyl transferase in Cos7 cells transiently expressed through TRalpha or TRalpha
      transfection. The results indicate that Kb430 lacks biological activity.

PMID- 22975596
TI  - Cultural adaptation, validation and development of a spanish brief version of the
      diabetes fear of injecting and self-testing questionnaire.
AB  - OBJECTIVE: To develop and validate in Spain a test to measure fear of injecting
      and selftesting [HIAT-I](c) in diabetic patients by translating and adapting the
      original English version of the Diabetes Fear of Injecting and Self-Testing
      Questionnaire (D-FISQ). PATIENTS AND METHOD: Forward-backward translations in
      duplicate were carried out and were revised by an expert and a nonexpert panel.
      Men and women with type 1 and type 2 diabetes aged more than 18 years old were
      enrolled in three primary care centers. The Spanish version of the D-FISQ was
      administered on two separate occasions at a 15-day interval. The trait-anxiety
      scale of the Stait-Trait Anxiety Inventory (STAI) and five specific questions on
      glycemic control, insulin injection, pain and worry were administered.
      Sociodemographic and clinical data were also collected. Feasibility, construct
      validity, concept validity and reliability were assessed. RESULTS: A 32-item
      version of the D-FISQ was developed by an expert panel and was administered to 93
      (35 Type 1, 58 Type 2) insulin-treated diabetic patients. Ninetynine per cent of
      the patients answered all items in 5 minutes (median). Item-total correlation and
      factor analysis led to an abridged, 19-item version, maintaining the two original
      dimensions, and explaining 47.4% percent of the total variance: fear of self
      injecting (FSI), accounting for 29.5% of the variance, and fear of self-testing
      (FST), accounting for 17.9%. Test-retest correlation coefficients were 0.85 (FSI)
      and 0.94 (FST). The correlations between STAI and FSI and FST were not
      statistically significant (p=0.771). The correlation coefficient between FSI and
      time under insulin treatment was -0.546 (p=0.023). CONCLUSIONS: We developed a
      newrecalibrated version of the Spanish D-FISQ called the MIAT-D. The feasibility,
      dimensionality, construct validity and reliability of this questionnaire were
      accurate. The concept validity of this test should be explored in further
      studies.

PMID- 22975597
TI  - PYY(1-36) and PYY(3-36) secretory response after a mixed meal in healthy
      individuals.
AB  - BACKGROUND: Peptide YY (PYY) is a 36 amino acid peptide synthesized mostly by
      intestinal L cells. This peptide reaches its nadir during fasting and increases
      immediately after meals. After food intake, two molecular forms are released,
      PYY(1-36) and PYY(3-36). PYY(3-36) reduces food intake in both humans and
      rodents. There is scarce information about plasmatic concentrations of PYY,
      especially of PYY(3-36), after food ingestion, and their relationship to ghrelin.
      OBJECTIVES: To study PYY(1-36) and PYY(3-36) secretory response after a mixed
      meal, and its relationship to total and acylated ghrelin secretion in healthy
      subjects. SUBJECTS AND METHOD: We studied eight healthy subjects, 4 women and 4
      men, with a median age of 53 (range, 36-59) years. After an overnight fast, the
      subjects received either a mixed standard meal (400ml Isosource Energy(r)
      [159kcal/100ml]) or placebo (400ml of water) orally in random order on two
      different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for
      measurement of PYY(1-36), PYY(3-36), total ghrelin and acylated ghrelin.
      Comparisons were made by Wilcoxon's test. Numerical correlations were performed
      using Spearman's test. P-values <= 0.05 were considered significant. RESULTS:
      After a mixed meal, PYY(1-36) reached a peak of (median [range]) 141.5 (81-198)
      pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml
      (p=0.04). The area under the curve (AUC) of PYY(1-36) levels after a mixed meal
      were 14,865 (8,032-19,822) pg/ml/min and after placebo were 8,992 (4,455-21,382)
      pg/ml/min (p=0.06). After ingestion of a mixed meal, PYY(3-36) reached a peak of
      92.5 (59-135) pg/ml, with no response to placebo (46.5 [30-66] pg/ml) (p = 0.02).
      The AUC of PYY(3-36) levels after a mixed meal were 9,086 (6,412-14,970)
      pg/ml/min, and after placebo were 4,984 (3,142-6,772) pg/ml/min (p=0.012). The
      quotient between nadir total ghrelin/peak PYY(1-36) was markedly diminished after
      food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial
      values of 3.55 (1.64-7.16) (p=0.03). The former quotient was unmodified by
      placebo. The quotient between nadir acylated ghrelin/peak PYY(3-36) was markedly
      diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92
      3) and postprandial values of 0.73 (0.26-1.27) (p=0.02). This quotient was
      unmodified by placebo. CONCLUSIONS: In healthy subjects, blood levels of both
      PYY(1-36) and PYY(3-36) increase after ingestion of a mixed meal. Simultaneously,
      total and acylated ghrelin levels diminish. The quotient between nadir acylated
      ghrelin/peak PYY(3-36) diminishes after a mixed meal. All these data suggest the
      possible contribution of these peptides to appetite regulation after ingestion.

PMID- 22975599
TI  - Rats fed the dietary supplement vitamix(r) (ceregumil(r) with vitamins) show
      greater physical resistance and antioxidant capacity.
AB  - OBJECTIVE: Vitamix(r) is a dietary product composed of a hydro-alcoholic extract
      of cereals and pulses with honey, calcium glycerophosphate, vitamins B and D,
      selenium and fluoride. The basic product, Ceregumil(r), patented in 1912, was
      highly popular as tonic and consumers reported a feeling of health, resistance to
      illness, and increased predisposition to work and exercise. MATERIAL AND METHOD:
      In the present study we analysed the effect of Vitamix(r) used as dietary
      supplement, on several physiological parameters in laboratory rats. We
      periodically performed hemograms and measured intake and weight, as well as blood
      levels of glucose, triglycerides, cholesterol, transaminases and malondialdehyde,
      a lipoperoxidation product. Physical probes were performed and a histochemical
      study was done in the liver. RESULTS: Rats fed with Vitamix(r) displayed lower
      intake and body weight in adult ages, showed and increased antioxidant activity,
      higher resistance in the wire hang test and lower fatigue in the Morris pool,
      specially those specimens considered as bad performers supplemented with
      Vitamix(r). The rest of the measured parameters remained similar to control and
      no hepatic alterations were found. CONCLUSIONS: This study supports a scientific
      basis to know the effect of these complements over physiological parameters.

PMID- 22975598
TI  - Inducible nitric oxide synthase (iNOS) expression in autoimmune thyroid disorders
      (AITD).
AB  - INTRODUCTION: Nitric oxide is synthesized by different cell types through the
      action of the enzyme nitric oxide synthase (NOS). There are four isoforms of this
      enzyme: the neuronal, the endothelial, the mitochondrial, and the inducible
      (iNOS) forms. Although NO production may play an important role in the
      pathogenesis of inflammation and tissue damage, its possible role in autoimmune
      thyroiditis has not been adequately explored. OBJECTIVE: To study protein and
      mRNA expression of iNOS in human autoimmune thyroid disorders (AITD). PATIENTS
      AND METHOD: We evaluated the expression of iNOS in thyroid gland specimens from
      10 patients with Graves' disease (GD), from five patients with Hashimoto's
      thyroiditis (HT) and from 10 controls by immunohistochemical and reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Both
      immunohistochemistry and PCR techniques showed up-regulated expression of iNOS in
      the thyroid glands of patients with GD and HT. iNOS expression was higher in GD
      than in HT. In contrast, no iNOS expression was detected in normal thyroid
      tissue. In both GD and HT, iNOS was detected in thyrocytes, mainly in those
      localized in areas close to the inflammatory cell infiltrate. In addition,
      upregulated expression of iNOS was observed in endothelial cells and
      thyroidinfiltrating mononuclear cells in both GD and HT. CONCLUSIONS: The
      enhanced expression of iNOS in autoimmune thyroiditis suggests that NO synthesis
      may play an important role in the inflammatory phenomena and tissue damage
      observed in this disease.

PMID- 22975600
TI  - Practical principles of home artificial nutrition.
AB  - Due to its multiple advantages, patient care at home is an expanding therapeutic
      modality. This therapeutic option benefits patients and their families by
      reducing the probability of complications related to length of hospital stay,
      such as nosocomial infections, as well as by offering the possibility of allowing
      patients to remain in the home environment, which is more comfortable.
      Furthermore, this treatment improves resource utilization by increasing hospital
      bed turnover. One of the modalities that is receiving increasing interest is home
      artificial nutrition. This treatment consists of administering nutrients and
      another therapeutic agents into a tube feeding (home enteral nutrition [HEN]) or
      through venous access (home parenteral nutrition [HPN]) to improve or to maintain
      the patient's nutritional status in the home environment. The present article
      aims to review some of the most interesting features of HAN related to the
      prevalence, legal framework, special situations in Spain and particular features
      of HEN and HPN (patient selection, diets, monitoring, complications). Lastly,
      this article analyzes the importance of education programs for patients and their
      families and of integration between the primary care and the specialist care
      teams for the success of this therapeutic modality, the aim of which is to
      improve quality of care. Home artificial nutrition is a necessary but underused
      modality in Spain compared with other, similar countries. However, the continual
      search for efficiency and quality in patient care will help to improve the
      provision of this therapeutic option in the near future.

PMID- 22975601
TI  - Silent corticotroph adenomas of the pituitary gland: apropos of two cases.
AB  - Clinically silent corticotroph adenomas are rare. The clinical course of these
      tumors varies: while some have an insidious course, others behave aggressively,
      especially during tumoral recurrence. Given the absence of clinical and
      biochemical features of hypercortisolism, the definitive diagnosis is
      histological.

PMID- 22975602
TI  - Hyperglycemia secondary to consumption of cocaine and atypical antipsychotic
      drugs.
AB  - Drugs such as cocaine and atypical antipsychotic agents, such as olanzapine, are
      sometimes related to hyperglycemia. Whereas cocaine raises plasma glucose through
      catecholamine release, atypical antipsychotic agents mainly increase appetite and
      induce weight gain and the development of metabolic syndrome. Moreover, the
      latter group of drugs also act independently from weight gain or adiposity, due
      to inhibition of beta pancreatic cells and reduction of peripheral insulin
      action. We present the case of a 29-year-old non-diabetic woman with severe acute
      hyperglycemia in the context of a suicide attempt through intake of olanzapine
      and cocaine. After discontinuation of olanzapine and cocaine consumption,
      glycemia was immediately normalized without subsequent diagnosis of diabetes.

PMID- 22975603
TI  - Hyperandrogenism in a postmenopausal woman.
AB  - Ovarian androgen hypersecretion is a wellrecognized cause of hirsutism and
      virilization in postmenopausal women. Postmenopausal ovarian hyperthecosis is a
      nonneoplastic functional disorder, which results from abnormal regulation of
      ovarian steroidogenesis. We present a patient with postmenopausal
      hyperandrogenism due to ovarian hyperthecosis.

PMID- 22975604
TI  - Patterns of disease recurrence following treatment of oropharyngeal cancer with
      intensity modulated radiation therapy.
AB  - PURPOSE: To report mature results of a large cohort of patients diagnosed with
      squamous cell carcinoma of the oropharynx who were treated with intensity
      modulated radiation therapy (IMRT). METHODS AND MATERIALS: The database of
      patients irradiated at The University of Texas, M.D. Anderson Cancer Center was
      searched for patients diagnosed with oropharyngeal cancer and treated with IMRT
      between 2000 and 2007. A retrospective review of outcome data was performed.
      RESULTS: The cohort consisted of 776 patients. One hundred fifty-nine patients
      (21%) were current smokers, 279 (36%) former smokers, and 337 (43%) never
      smokers. T and N categories and American Joint Committee on Cancer group stages
      were distributed as follows: T1/x, 288 (37%); T2, 288 (37%); T3, 113 (15%); T4,
      87 (11%); N0, 88(12%); N1/x, 140 (18%); N2a, 101 (13%); N2b, 269 (35%); N2c, 122
      (16%); and N3, 56 (7%); stage I, 18(2%); stage II, 40(5%); stage III, 150(19%);
      and stage IV, 568(74%). Seventy-one patients (10%) presented with nodes in level
      IV. Median follow-up was 54 months. The 5-year overall survival, locoregional
      control, and overall recurrence-free survival rates were 84%, 90%, and 82%,
      respectively. Primary site recurrence developed in 7% of patients, and neck
      recurrence with primary site control in 3%. We could only identify 12 patients
      (2%) who had locoregional recurrence outside the high-dose target volumes. Poorer
      survival rates were observed in current smokers, patients with larger primary (T)
      tumors and lower neck disease. CONCLUSIONS: Patients with oropharyngeal cancer
      treated with IMRT have excellent disease control. Locoregional recurrence was
      uncommon, and most often occurred in the high dose volumes. Parotid sparing was
      accomplished in nearly all patients without compromising tumor coverage.

PMID- 22975605
TI  - A voluntary breath-hold treatment technique for the left breast with unfavorable
      cardiac anatomy using surface imaging.
AB  - PURPOSE: Breath-hold (BH) treatments can be used to reduce cardiac dose for
      patients with left-sided breast cancer and unfavorable cardiac anatomy. A surface
      imaging technique was developed for accurate patient setup and reproducible real
      time BH positioning. METHODS AND MATERIALS: Three-dimensional surface images were
      obtained for 20 patients. Surface imaging was used to correct the daily setup for
      each patient. Initial setup data were recorded for 443 fractions and were
      analyzed to assess random and systematic errors. Real time monitoring was used to
      verify surface placement during BH. The radiation beam was not turned on if the
      BH position difference was greater than 5 mm. Real-time surface data were
      analyzed for 2398 BHs and 363 treatment fractions. The mean and maximum
      differences were calculated. The percentage of BHs greater than tolerance was
      calculated. RESULTS: The mean shifts for initial patient setup were 2.0 mm, 1.2
      mm, and 0.3 mm in the vertical, longitudinal, and lateral directions,
      respectively. The mean 3-dimensional vector shift was 7.8 mm. Random and
      systematic errors were less than 4 mm. Real-time surface monitoring data
      indicated that 22% of the BHs were outside the 5-mm tolerance (range, 7%-41%),
      and there was a correlation with breast volume. The mean difference between the
      treated and reference BH positions was 2 mm in each direction. For out-of
      tolerance BHs, the average difference in the BH position was 6.3 mm, and the
      average maximum difference was 8.8 mm. CONCLUSIONS: Daily real-time surface
      imaging ensures accurate and reproducible positioning for BH treatment of left
      sided breast cancer patients with unfavorable cardiac anatomy.

PMID- 22975606
TI  - Results of a phase 2 study examining the effects of omitting elective neck
      irradiation to nodal levels IV and Vb in patients with N(0-1) nasopharyngeal
      carcinoma.
AB  - PURPOSE: To evaluate the patterns of nodal failure and toxicity in clinically
      negative necks of N0-1 nasopharyngeal carcinoma (NPC) patients who were treated
      with intensity modulated radiation therapy (IMRT) but did not receive elective
      neck irradiation (ENI) to level IV and Vb nodes. METHODS AND MATERIALS: We
      conducted a phase 2 prospective study in N0-1 NPC patients treated with IMRT. ENI
      included the retropharyngeal nodes and levels II to Va but omitted levels IV and
      Vb in clinically negative necks. Patterns of nodal failure, regional control
      (RC), and late toxicity were evaluated. RESULTS: Between 2001 and 2008, a total
      of 212 patients (128 N0 and 84 N1) were enrolled in the study. Seven patients (4
      in-field and 3 out-of-field) developed nodal failure. One patient (0.5%)
      developed nodal failure at level Vb, but no patients developed nodal failure at
      level IV. The 5-year RC rates of the entire group, N0 patients and N1 patients
      were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed
      distant metastases. The 5-year distant failure-free survival (DFFS) and overall
      survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or
      greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%,
      and 17.9%, respectively. CONCLUSIONS: The rate of out-of-field nodal failure when
      omitting ENI to levels IV and Vb in clinically negative necks of patients with N0
      1 NPC was extremely low; therefore, a further phase 3 study is warranted.

PMID- 22975608
TI  - Dose and spatial effects in long-distance radiation signaling in vivo:
      implications for abscopal tumorigenesis.
AB  - PURPOSE: To investigate the dose and spatial dependence of abscopal radiation
      effects occurring in vivo in the mouse, along with their tumorigenic potential in
      the central nervous system (CNS) of a radiosensitive mouse model. METHODS AND
      MATERIALS: Patched1 (Ptch1)(+/-) mice, carrying a germ-line heterozygous
      inactivating mutation in the Ptch1 gene and uniquely susceptible to radiation
      damage in neonatal cerebellum, were exposed directly to ionizing radiation (1, 2,
      or 3 Gy of x-rays) or treated in a variety of partial-body irradiation protocols,
      in which the animals' head was fully protected by suitable lead cylinders while
      the rest of the body was exposed to x-rays in full or in part. Apoptotic cell
      death was measured in directly irradiated and shielded cerebellum shortly after
      irradiation, and tumor development was monitored in lifetime groups. The same
      endpoints were measured using different shielding geometries in mice irradiated
      with 3 or 10 Gy of x-rays. RESULTS: Although dose-dependent cell death was
      observed in off-target cerebellum for all doses and shielding conditions tested,
      a conspicuous lack of abscopal response for CNS tumorigenesis was evident at the
      lowest dose of 1 Gy. By changing the amount of exposed body volume, the shielding
      geometry could also significantly modulate tumorigenesis depending on dose.
      CONCLUSIONS: We conclude that interplay between radiation dose and exposed tissue
      volume plays a critical role in nontargeted effects occurring in mouse CNS under
      conditions relevant to humans. These findings may help understanding the
      mechanisms of long-range radiation signaling in harmful effects, including
      carcinogenesis, occurring in off-target tissues.

PMID- 22975607
TI  - Spine radiosurgery: a dosimetric analysis in 124 patients who received 18 Gy.
AB  - PURPOSE: To define the safely tolerated doses to organs at risk (OARs) adjacent
      to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single
      fraction. METHODS AND MATERIALS: A total of 124 patient cases with 165 spine
      metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the
      90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal
      cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were
      analyzed. RESULTS: A total of 124 patients (100%) were followed-up, and median
      follow-up time was 7 months (1-50 months). Symptoms and local control were
      achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG)
      grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for
      oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2
      4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of
      the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord
      maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume
      receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33
      cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the
      TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34)
      received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc),
      2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2
      cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. CONCLUSIONS: Cord
      Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single
      fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15
      of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and
      V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.

PMID- 22975609
TI  - Radiation-induced alterations in mouse brain development characterized by
      magnetic resonance imaging.
AB  - PURPOSE: The purpose of this study was to identify regions of altered development
      in the mouse brain after cranial irradiation using longitudinal magnetic
      resonance imaging (MRI). METHODS AND MATERIALS: Female C57Bl/6 mice received a
      whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI
      was performed before irradiation and at 3 time points following irradiation.
      Deformation-based morphometry was used to quantify volume and growth rate changes
      following irradiation. RESULTS: Widespread developmental deficits were observed
      in both white and gray matter regions following irradiation. Most of the affected
      brain regions suffered an initial volume deficit followed by growth at a normal
      rate, remaining smaller in irradiated brains compared with controls at all time
      points examined. The one exception was the olfactory bulb, which in addition to
      an early volume deficit, grew at a slower rate thereafter, resulting in a
      progressive volume deficit relative to controls. Immunohistochemical assessment
      revealed demyelination in white matter and loss of neural progenitor cells in the
      subgranular zone of the dentate gyrus and subventricular zone. CONCLUSIONS: MRI
      can detect regional differences in neuroanatomy and brain growth after whole
      brain irradiation in the developing mouse. Developmental deficits in neuroanatomy
      persist, or even progress, and may serve as useful markers of late effects in
      mouse models. The high-throughput evaluation of brain development enabled by
      these methods may allow testing of strategies to mitigate late effects after
      pediatric cranial irradiation.

PMID- 22975610
TI  - Radiation therapy for neovascular age-related macular degeneration.
AB  - In the enormity of the public health burden imposed by age-related macular
      degeneration (ARMD), much effort has been directed toward identifying effective
      and efficient treatments. Currently, anti-vascular endothelial growth factor
      (VEGF) injections have demonstrated considerably efficacy in treating neovascular
      ARMD, but patients require frequent treatment to fully benefit. Here, we review
      the rationale and evidence for radiation therapy of ARMD. The results of early
      photon external beam radiation therapy are included to provide a framework for
      the sequential discussion of evidence for the usage of stereotactic radiation
      therapy, proton therapy, and brachytherapy. The evidence suggests that these 3
      modern modalities can provide a dose-dependent benefit in the treatment of ARMD.
      Most importantly, preliminary data suggest that all 3 can be used in conjunction
      with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF
      injections required to maintain visual acuity.

PMID- 22975611
TI  - Comparative effectiveness of 5 treatment strategies for early-stage non-small
      cell lung cancer in the elderly.
AB  - PURPOSE: The incidence of early-stage non-small cell lung cancer (NSCLC) among
      older adults is expected to increase because of demographic trends and computed
      tomography-based screening; yet, optimal treatment in the elderly remains
      controversial. Using the Surveillance, Epidemiology, and End Results (SEER)
      Medicare cohort spanning 2001-2007, we compared survival outcomes associated with
      5 strategies used in contemporary practice: lobectomy, sublobar resection,
      conventional radiation therapy, stereotactic ablative radiation therapy (SABR),
      and observation. METHODS AND MATERIALS: Treatment strategy and covariates were
      determined in 10,923 patients aged >= 66 years with stage IA-IB NSCLC. Cox
      regression, adjusted for patient and tumor factors, compared overall and disease
      specific survival for the 5 strategies. In a second exploratory analysis,
      propensity-score matching was used for comparison of SABR with other options.
      RESULTS: The median age was 75 years, and 29% had moderate to severe
      comorbidities. Treatment distribution was lobectomy (59%), sublobar resection
      (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In
      Cox regression analysis with a median follow-up time of 3.2 years, SABR was
      associated with the lowest risk of death within 6 months of diagnosis (hazard
      ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy).
      After 6 months, lobectomy was associated with the best overall and disease
      specific survival. In the propensity-score matched analysis, survival after SABR
      was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is
      SABR). Conventional radiation and observation were associated with poor outcomes
      in all analyses. CONCLUSIONS: In this population-based experience, lobectomy was
      associated with the best long-term outcomes in fit elderly patients with early
      stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy
      comparable with that of surgery in select populations. Evaluation of these
      therapies in randomized trials is urgently needed.

PMID- 22975612
TI  - Role of early proctoscopy in predicting late symptomatic proctitis after external
      radiation therapy for prostate carcinoma.
AB  - PURPOSE: To determine whether acute radiation-proctitis, diagnosed by proctoscopy
      after radiation therapy for prostate cancer, can predict late clinical proctitis.
      METHODS AND MATERIALS: A prospective study of 130 patients who underwent external
      radiation therapy (RT) for stage T1 to T4 prostate cancer between 1997 and 2008
      was performed. Treatments were conventional (2-dimensional [2D]) in 61 patients
      and 3D conformal in 69, with a median target dose of 72 Gy (70-74 Gy). Within 1
      week after RT, proctoscopy was performed to detect possible acute endoscopic
      proctitis (AEP). Acute clinical proctitis (ACP) and late clinical proctitis (LCP)
      were also evaluated. The median follow-up was 84 months (20-180 months). The
      influence of AEP and ACP on LCP occurrence was studied using the Cox model
      controlling for age, dose, prostatectomy, RT technique (2D vs 3D), and hormone
      therapy. RESULTS: AEP was detected in 15 patients (11.5%) and ACP in 67 (51.5%);
      in 13 cases (10%) AEP and ACP occurred simultaneously. Thirty-five cases of LCP
      were recorded. The 5-year probability of developing LCP was highest in patients
      with AEP and ACP (77%, 95% confidence interval [CI] 53%-94%) and lowest in
      asymptomatic patients (14%, 95% CI 7%-26%; P<.001). Compared to asymptomatic
      patients, the 5-year probability also was slightly increased in patients with ACP
      only (26%, 95% CI 16%-40%; P=.052). In multivariable analysis, the combination of
      AEP and ACP was the main predictor of LCP: compared to asymptomatic patients, the
      hazard ratio was 5.6 (2.1-15.2) in patients with AEP plus ACP (P=.001) and 2.1
      (0.9-4.9) in those with ACP only (P=.103). CONCLUSIONS: In patients with AEP and
      ACP, the risk of LCP was more than 5-fold increased compared to those who were
      asymptomatic, while a much smaller increase in risk occurred in patients with ACP
      only. Early proctoscopy can provide valuable information regarding the likelihood
      of late proctitis.

PMID- 22975613
TI  - Kilovoltage intrafraction monitoring for prostate intensity modulated arc
      therapy: first clinical results.
AB  - PURPOSE: Most linear accelerators purchased today are equipped with a gantry
      mounted kilovoltage X-ray imager which is typically used for patient imaging
      prior to therapy. A novel application of the X-ray system is kilovoltage
      intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is
      determined during treatment. In this paper, we report on the first use of KIM in
      a prospective clinical study of prostate cancer patients undergoing intensity
      modulated arc therapy (IMAT). METHODS AND MATERIALS: Ten prostate cancer patients
      with implanted fiducial markers undergoing conventionally fractionated IMAT
      (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves
      acquiring kV images as the gantry rotates around the patient during treatment.
      Post-treatment, markers in these images were segmented to obtain 2D positions.
      From the 2D positions, a maximum likelihood estimation of a probability density
      function was used to obtain 3D prostate trajectories. The trajectories were
      analyzed to determine the motion type and the percentage of time the prostate was
      displaced >= 3, 5, 7, and 10 mm. Independent verification of KIM positional
      accuracy was performed using kV/MV triangulation. RESULTS: KIM was performed for
      268 fractions. Various prostate trajectories were observed (ie, continuous target
      drift, transient excursion, stable target position, persistent excursion, high
      frequency excursions, and erratic behavior). For all patients, 3D displacements
      of >= 3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time,
      respectively. The average systematic accuracy of KIM was measured at 0.46 mm.
      CONCLUSIONS: KIM for prostate IMAT was successfully implemented clinically for
      the first time. Key advantages of this method are (1) submillimeter accuracy, (2)
      widespread applicability, and (3) a low barrier to clinical implementation. A
      disadvantage is that KIM delivers additional imaging dose to the patient.

PMID- 22975614
TI  - Detection of esophageal fiducial marker displacement during radiation therapy
      with a 2-dimensional on-board imager: analysis of internal margin for esophageal
      cancer.
AB  - PURPOSE: To quantify the interfraction displacement of esophageal fiducial
      markers for primary esophageal cancer radiation therapy. METHODS AND MATERIALS:
      Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed
      in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic
      clipping as fiducial metal markers. Displacement of the markers between the
      digitally reconstructed radiographs and on-board kilovoltage images during
      radiation therapy was analyzed according to direction and esophageal site.
      RESULTS: Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29
      distal), underwent 367 2D matching sessions during radiation therapy. The mean
      (SD) absolute marker displacement was 0.26 (0.30) cm in the right-left (RL), 0.50
      (0.39) cm in the superior-inferior (SI), and 0.24 (0.21) cm in the anterior
      posterior (AP) direction. Displacement was significantly larger in the SI than in
      the RL and AP directions (P<.0001). In the SI direction, mean absolute
      displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm,
      0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement
      was significantly larger than those of the middle and proximal esophagus
      (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in
      the RL and AP directions. In the SI direction, the margin was 1.25 cm for the
      proximal and middle esophagus and 1.75 cm for the distal esophagus. CONCLUSIONS:
      The magnitude of interfraction displacement of esophageal clips was larger in the
      SI direction, particularly in the distal esophagus, but substantial displacement
      was observed in other directions and at other esophageal sites. It is practical
      to take estimated movements into account with internal margins, even if vertebrae
      based 2D matching is performed.

PMID- 22975615
TI  - Impact of margin status on local recurrence after mastectomy for ductal carcinoma
      in situ.
AB  - PURPOSE: To examine the rate of local recurrence according to the margin status
      for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy.
      METHODS AND MATERIALS: One hundred forty-five consecutive women who underwent
      mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were
      included in this retrospective analysis. Only patients with pure DCIS were
      eligible; patients with microinvasion were excluded. The primary endpoint was
      local recurrence, defined as recurrence on the chest wall; regional and distant
      recurrences were secondary endpoints. Outcomes were analyzed according to margin
      status (positive, close (<=2 mm), or negative), location of the closest margin
      (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of
      mastectomy, and receipt of hormonal therapy. RESULTS: The primary cohort
      consisted of 142 patients who did not receive postmastectomy radiation therapy
      (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6
      13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients
      (16%) had a close (<=2 mm) margin. The deep margin was close in 14 patients and
      positive in 6 patients. The superficial margin was close in 13 patients and
      positive in 19 patients. One patient experienced an isolated invasive chest wall
      recurrence, and 1 patient had simultaneous chest wall, regional nodal, and
      distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%)
      for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for
      those with close margins, and 0/98 for patients with negative margins. PMRT was
      given as part of the initial treatment to 3 patients, 1 of whom had an isolated
      chest wall recurrence. CONCLUSIONS: Mastectomy for pure DCIS resulted in a low
      rate of local or distant recurrences. Even with positive or close mastectomy
      margins, the rates of chest wall recurrences were so low that PMRT is likely not
      warranted.

PMID- 22975616
TI  - Phase 3 trial of postoperative chemotherapy alone versus chemoradiation therapy
      in stage III-IV gastric cancer treated with R0 gastrectomy and D2 lymph node
      dissection.
AB  - PURPOSE: To compare chemotherapy alone with chemoradiation therapy in stage III
      IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.
      METHODS AND MATERIALS: The chemotherapy arm received 5 cycles of fluorouracil and
      leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then
      radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles
      of FL. Intent-to-treat analysis and per-protocol analyses were performed.
      RESULTS: Between May 6, 2002 and June 29, 2006, a total of 90 patients were
      enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the
      chemoradiation therapy arm. Treatment was completed as planned by 93.2% of
      patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm.
      Overall intent-to-treat analysis showed that addition of radiation therapy to
      chemotherapy significantly improved locoregional recurrence-free survival (LRRFS)
      but not disease-free survival. In subgroup analysis for stage III, chemoradiation
      therapy significantly prolonged the 5-year LRRFS and disease-free survival rates
      compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056,
      respectively). CONCLUSIONS: Addition of radiation therapy to chemotherapy could
      improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2
      lymph node dissection.

PMID- 22975617
TI  - Physiological interaction of heart and lung in thoracic irradiation.
AB  - INTRODUCTION: The risk of early radiation-induced lung toxicity (RILT) limits the
      dose and efficacy of radiation therapy of thoracic tumors. In addition to lung
      dose, coirradiation of the heart is a known risk factor in the development RILT.
      The aim of this study was to identify the underlying physiology of the
      interaction between lung and heart in thoracic irradiation. METHODS AND
      MATERIALS: Rat hearts, lungs, or both were irradiated to 20 Gy using high
      precision proton beams. Cardiopulmonary performance was assessed using breathing
      rate measurements and F(18)-fluorodeoxyglucose positron emission tomography
      ((18)F-FDG-PET) scans biweekly and left- and right-sided cardiac hemodynamic
      measurements and histopathology analysis at 8 weeks postirradiation. RESULTS: Two
      to 12 weeks after heart irradiation, a pronounced defect in the uptake of (18)F
      FDG in the left ventricle (LV) was observed. At 8 weeks postirradiation, this
      coincided with LV perivascular fibrosis, an increase in LV end-diastolic
      pressure, and pulmonary edema in the shielded lungs. Lung irradiation alone not
      only increased pulmonary artery pressure and perivascular edema but also induced
      an increased LV relaxation time. Combined irradiation of lung and heart induced
      pronounced increases in LV end-diastolic pressure and relaxation time, in
      addition to an increase in right ventricle end-diastolic pressure, indicative of
      biventricular diastolic dysfunction. Moreover, enhanced pulmonary edema,
      inflammation and fibrosis were also observed. CONCLUSIONS: Both lung and heart
      irradiation cause cardiac and pulmonary toxicity via different mechanisms. Thus,
      when combined, the loss of cardiopulmonary performance is intensified further,
      explaining the deleterious effects of heart and lung coirradiation. Our findings
      show for the first time the physiological mechanism underlying the development of
      a multiorgan complication, RILT. Reduction of dose to either of these organs
      offers new opportunities to improve radiation therapy treatment of thoracic
      tumors, potentially facilitating increased treatment doses and tumor control.

PMID- 22975618
TI  - Role of interleukin-6 in the radiation response of liver tumors.
AB  - PURPOSE: To investigate the role of interleukin (IL)-6 in biological sequelae and
      tumor regrowth after irradiation for hepatic malignancy, which are critical for
      the clinical radiation response of liver tumors. METHODS AND MATERIALS: The Hepa
      1-6 murine hepatocellular cancer cell line was used to examine the radiation
      response by clonogenic assays and tumor growth delay in vivo. After irradiation
      in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including
      cell death and tumor regrowth were examined by experimental manipulation of IL-6
      signaling. The effects of blocking IL-6 were assessed by cells preincubated in
      the presence of IL-6-neutralizing antibody for 24 hours or stably transfected
      with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels,
      and myeloid-derived suppressor cells (MDSC) recruitment were examined using
      animal experiments. RESULTS: Interleukin-6 expression was positively linked to
      irradiation and radiation resistance, as demonstrated by in vitro and in vivo
      experiments. Interleukin-6-silencing vectors induced more tumor inhibition and
      DNA damage after irradiation. When subjects were irradiated with a sublethal
      dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels
      and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome
      irradiation-induced MDSC recruitment and tumor regrowth after treatment.
      CONCLUSION: These data demonstrate that IL-6 is important in determining the
      radiation response of liver tumor cells. Irradiation-induced IL-6 and the
      subsequent recruitment of MDSC could be responsible for tumor regrowth.
      Therefore, treatment with concurrent IL-6 inhibition could be a potential
      therapeutic strategy for increasing the radiation response of tumors.

PMID- 22975619
TI  - Hepatocytes determine the hypoxic microenvironment and radiosensitivity of
      colorectal cancer cells through production of nitric oxide that targets
      mitochondrial respiration.
AB  - PURPOSE: To determine whether host hepatocytes may reverse hypoxic
      radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model
      relevant to colorectal cancer (CRC) liver metastases. METHODS AND MATERIALS:
      Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture
      system with diffusion-limited oxygenation, and oxygen levels were monitored by an
      oxygen-sensing fluorescence probe. To activate endogenous NO production,
      cocultures were exposed to a cytokine mixture, and the expression of inducible
      nitric oxide synthase was analyzed by reverse transcription-polymerase chain
      reaction, Western blotting, and NO/nitrite production. The mitochondrial targets
      of NO were examined by enzymatic activity. To assess hypoxic radioresponse,
      cocultures were irradiated and reseeded for colonies. RESULTS: Resting
      hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1,
      HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of
      hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of
      tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized
      all CRC cell lines more than 1.5-fold, similar to the effect of selective
      mitochondrial inhibitors. The radiosensitizing effect was associated with a
      respiratory self-arrest of hepatocytes at the level of aconitase and complex II,
      which resulted in profound reoxygenation of tumor cells through oxygen sparing.
      Nitric oxide-producing hepatocytes were at least 10 times more active than NO
      producing macrophages to reverse hypoxia-induced radioresistance. CONCLUSIONS:
      Hepatocytes were the major determinants of the hypoxic microenvironment and
      radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence
      that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved
      through oxygen sparing induced by endogenous NO production in host hepatocytes.

PMID- 22975620
TI  - Developmental lead acetate exposure induces embryonic toxicity and memory deficit
      in adult zebrafish.
AB  - Lead is a persistent metal and commonly present in our living environment. The
      present study was aimed to investigate lead-induced embryonic toxicity,
      behavioral responses, and adult learning/memory deficit in zebrafish. Lead
      acetate (PbAc) induced malformations such as uninflated swim bladder, bent spine
      and yolk-sac edema with an EC50 of 0.29 mg/L at 120 h post fertilization (hpf).
      Spontaneous movement as characterized by tail bend frequency was significantly
      altered in zebrafish embryos following exposure to PbAc. Behavior assessment
      demonstrated that lead exposure changed behavioral responses in zebrafish larvae,
      as hyperactivity was detected within the first minute of light-to-dark transition
      in the fish exposed to PbAc from 6 to 96 hpf, and a different dose-dependent
      change was found in swimming speeds in the dark and in the light at 120 hpf
      following lead exposure. Learning/memory task assay showed that embryos exposed
      to PbAc from 6 to 120 hpf developed learning/memory deficit at adulthood as
      exhibited by a significant decrease in accuracy rate to find the food and a
      significant increase in finding time. Overall, our results suggested that low
      dose of developmental lead exposure resulted in embryonic toxicity, behavioral
      alteration, and adult learning/memory deficit in zebrafish.

PMID- 22975621
TI  - Urinary p-cresol in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a neuropsychiatric disorder with onset during
      early childhood and life-long consequences in most cases. It is characterized by
      impairment in social interaction and communication, as well as by restricted
      patterns of interest and stereotyped behaviors. The etiology of autism is highly
      heterogeneous, encompassing a large range of genetic and environmental factors.
      Several lines of evidence suggest that, in addition to broader diagnostic
      criteria and increased awareness, also a real increase in incidence primarily due
      to greater gene-environment interactions may also be occurring. Environmental
      exposure to the organic aromatic compound p-cresol (4-methylphenol) is relatively
      common and occurs through the skin, as well as the gastrointestinal and
      respiratory systems. However, the largest and most widespread source of this
      compound is represented by some gut bacteria which express p-cresol synthesizing
      enzymes not found in human cells. Urinary p-cresol and its conjugated derivative
      p-cresylsulfate have been found elevated in an initial sample and recently in a
      replica sample of autistic children below 8 years of age, where it is associated
      with female sex, greater clinical severity regardless of sex, and history of
      behavioral regression. Potential sources of p-cresol excess in ASD, such as gut
      infection, chronic constipation, antibiotics, abnormal intestinal permeability,
      and environmental exposure, are being investigated. P-cresol may contribute to
      worsen autism severity and gut dysfunction, often present in autistic children.
      It may also contribute to a multibiomarker diagnostic panel useful in small
      autistic children.

PMID- 22975622
TI  - Nanoporous metals: fabrication strategies and advanced electrochemical
      applications in catalysis, sensing and energy systems.
AB  - Nanoporous metals, a representative type of nanostructured material, possess
      intriguing properties to generate enormously promising potentials for various
      important applications. In particular, with the advances of fabrication
      strategies, nanoporous metals with a variety of superior properties including
      unique pore structure, large specific surface area and high electrical
      conductivity have fuelled up great interests to explore their electrocatalytic
      properties and greatly extend their emerging applications in electrochemical
      sensing and energy systems. This tutorial review attempts to summarize the recent
      important progress towards the development of nanoporous metals, with special
      emphasis on fabrication methods and advanced electrochemical applications, such
      as electrocatalysts, chemical sensors and energy systems. Key scientific issues
      and prospective directions of research are also discussed.

PMID- 22975623
TI  - Endovascular palliation of multivessel blowout syndrome in the setting of a
      nonresectable neck sarcoma.
AB  - Carotid blowout syndrome is a rare life-threatening complication of head and neck
      malignancy. Current literature has focused exclusively on the carotid system and
      associated branches. We present a unique case of multivessel blowout in the
      setting of a large nonresectable neck sarcoma requiring various endovascular
      techniques for palliation.

PMID- 22975624
TI  - Peptide linkers for the immobilization of bioactive molecules on biphasic calcium
      phosphate via a modular immobilization system.
AB  - Herein we describe the use of peptide linkers to establish a nucleic acid-based
      immobilization system based on biphasic calcium phosphates (BCP), with which
      different molecules can be immobilized at the same time in defined ratios. It
      consists of single-stranded oligonucleotides, anchor strands (AS) which are
      immobilized to the surface and conjugates of complementary strands (CS) and
      bioactive molecules that bind to the AS via Watson-Crick base pairing. AS
      immobilization can be achieved on calcium phosphate ceramics using conjugates of
      AS and peptides that bind specifically to the ceramic. We successfully
      immobilized three different peptide sequences on BCP. Among them, we identified
      Stath (DpSpS EEK FLR RIG RFG, phosphoserine) as the most suitable one and further
      immobilized Stath-AS conjugates on BCP. This immobilized AS was able to hybridize
      with CS. Unspecific adsorption of oligonucleotides on the BCP surface was
      negligible. The stability of the system was proven by short term desorption
      experiments. The amounts of immobilized peptides, oligonucleotides and peptide-AS
      conjugates were determined by an enzymatic assay using biotin-streptavidin
      interactions, and were found to reach surface densities that are of therapeutic
      relevance (0.03 pmol cm(-2)).

PMID- 22975625
TI  - Resorbable, amino acid-based poly(ester urea)s crosslinked with osteogenic growth
      peptide with enhanced mechanical properties and bioactivity.
AB  - Materials currently used for the treatment of bone defects include ceramics,
      polymeric scaffolds and composites, which are often impregnated with recombinant
      growth factors and other bioactive substances. While these materials have seen
      instances of success, each has inherent shortcomings including prohibitive
      expense, poor protein stability, poorly defined growth factor release and less
      than desirable mechanical properties. We have developed a novel class of amino
      acid-based poly(ester urea)s (PEU) materials which are biodegradable in vivo and
      possess mechanical properties superior to conventionally used polyesters (<3.5
      GPa) available currently to clinicians and medical providers. We report the use
      of a short peptide derived from osteogenic growth peptide (OGP) as a covalent
      crosslinker for the PEU materials. In addition to imparting specific bioactive
      signaling, our crosslinking studies show that the mechanical properties increase
      proportionally when 0.5% and 1.0% concentrations of the OGP crosslinker are
      added. Our results in vitro and in an in vivo subcutaneous rat model show the OGP
      based crosslinkers, which are small fragments of growth factors that are normally
      soluble, exhibit enhanced proliferative activity, accelerated degradation
      properties and concentration dependent bioactivity when immobilized.

PMID- 22975626
TI  - Vegetable oil thermosets reinforced by tannin-lipid formulations.
AB  - Totally bio-based thermosetting polymers which are comparable to synthetic
      polyester thermosets have been prepared from copolymerization of condensed tannin
      fatty acid esters with vegetable oils. Oxidative copolymerization of tannin
      linoleate/acetate mixed esters with linseed oil and tung oil produced polymer
      films ranging from soft rubbers to rigid thermosets. Tannin incorporation into
      the formulations was essential for the final product to achieve necessary
      mechanical strength. Films had ambient modulus values between 0.12 and 1.6 GPa,
      with glass transition temperatures ranging from 32 to 72  degrees C and
      calculated crosslink densities of 1020-57,700 mol m-3. Film stiffness, T(g) and
      crosslink density increase with greater tannin linoeate/acetate content due
      mainly to this tannin component providing rigidity through polyphenolic aromatic
      rings and unsaturated chains as crosslinking sites.

PMID- 22975627
TI  - Volume change of double cross-linked poly(aspartic acid) hydrogels induced by
      cleavage of one of the crosslinks.
AB  - In the present paper we report for the first time the development of redox
      responsive biocompatible polymer gels. Double cross-linked poly(aspartic acid)
      hydrogels were prepared using two different cross-linking agents simultaneously.
      One of the cross-linkers was diaminobutane (DAB), the other cystamine (CYS). The
      relative amounts of DAB and CYS molecules were varied over a wide range while the
      total amount of cross-linker molecules (DAB+CYS) was kept constant. DAB provides
      stable cross-links, whereas CYS contains disulfide bonds, which can be broken by
      reduction. The cleavage of disulfide cross-links results in enhanced swelling and
      a significant decrease in the elastic modulus of the gels. These novel types of
      stimuli-responsive gels are promising candidates for new swelling controlled
      release matrices.

PMID- 22975629
TI  - A genetic algorithm for optimizing multi-pole Debye models of tissue dielectric
      properties.
AB  - Models of tissue dielectric properties (permittivity and conductivity) enable the
      interactions of tissues and electromagnetic fields to be simulated, which has
      many useful applications in microwave imaging, radio propagation, and non
      ionizing radiation dosimetry. Parametric formulae are available, based on a multi
      pole model of tissue dispersions, but although they give the dielectric
      properties over a wide frequency range, they do not convert easily to the time
      domain. An alternative is the multi-pole Debye model which works well in both
      time and frequency domains. Genetic algorithms are an evolutionary approach to
      optimization, and we found that this technique was effective at finding the best
      values of the multi-Debye parameters. Our genetic algorithm optimized these
      parameters to fit to either a Cole-Cole model or to measured data, and worked
      well over wide or narrow frequency ranges. Over 10 Hz-10 GHz the best fits for
      muscle, fat or bone were each found for ten dispersions or poles in the multi
      Debye model. The genetic algorithm is a fast and effective method of developing
      tissue models that compares favourably with alternatives such as the rational
      polynomial fit.

PMID- 22975628
TI  - Enhanced cellular adhesion on titanium by silk functionalized with titanium
      binding and RGD peptides.
AB  - Soft tissue adhesion on titanium represents a challenge for implantable
      materials. In order to improve adhesion at the cell/material interface we used a
      new approach based on the molecular recognition of titanium by specific peptides.
      Silk fibroin protein was chemically grafted with titanium binding peptide (TiBP)
      to increase adsorption of these chimeric proteins to the metal surface. A quartz
      crystal microbalance was used to quantify the specific adsorption of TiBP
      functionalized silk and an increase in protein deposition by more than 35% was
      demonstrated due to the presence of the binding peptide. A silk protein grafted
      with TiBP and fibronectin-derived arginine-glycine-aspartic acid (RGD) peptide
      was then prepared. The adherence of fibroblasts on the titanium surface modified
      with the multifunctional silk coating demonstrated an increase in the number of
      adhering cells by 60%. The improved adhesion was demonstrated by scanning
      electron microscopy and immunocytochemical staining of focal contact points.
      Chick embryo organotypic culture also revealed strong adhesion of endothelial
      cells expanding on the multifunctional silk peptide coating. These results
      demonstrated that silk functionalized with TiBP and RGD represents a promising
      approach to modify cell-biomaterial interfaces, opening new perspectives for
      implantable medical devices, especially when reendothelialization is required.

PMID- 22975630
TI  - Methylseleninic acid (MSA) inhibits 17beta-estradiol-induced cell growth in
      breast cancer T47D cells via enhancement of the antioxidative thioredoxin/
      thioredoxin reductase system.
AB  - The purpose of this study was to clarify the cell growth inhibitory mechanism of
      human breast cancer cells caused by selenium (Se) compounds. In the presence of
      17beta-estradiol (E(2)) at physiological concentrations, growth of estrogen
      receptor alpha (ERalpha)-positive T47D cells was markedly inhibited by 1 * 10(-6)
      mol/L methylseleninic acid (MSA) with no Se related toxicity.Under conditions
      where cell growth was inhibited, MSA decreased ERalpha mRNA levels and subsequent
      protein levels; further decreasing expression of estrogen-responsive finger
      protein (Efp) which is a target gene product of ERalpha and promotes G2/M
      progression of the cell cycle. Therefore, the decline in Efp expression is
      presumed to be involved in G2 arrest. Coincidentally, the antioxidative
      thioredoxin/ thioredoxin reductase (Trx/TrxR) system in cells was enhanced by the
      synergistic action of E(2) and MSA. It has been reported that ROS-induced
      oxidative stress enhanced ERalpha expression. E(2) increased production of
      intracellular ROS in T47D cells. Meanwhile, MSA significantly decreased E(2)
      induced ROS accumulation. From these results, activation of the Trx/TrxR system
      induced by the coexistence of MSA and E(2) suppresses oxidative stress and
      decreases expression of ERalpha, and finally induces the growth arrest of T47D
      cells through disruption of ERalpha signaling.

PMID- 22975632
TI  - PMA-induced GCMa phosphorylation stimulates its transcriptional activity and
      degradation.
AB  - Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM
      transcription factor family and plays critical roles in trophoblast
      differentiation and placental functions. It is well established that the cyclic
      AMP (cAMP)-dependent pathway induces the expression and transcriptional activity
      of GCMa by regulating post-translational modifications of GCMa, which results in
      enhancement of trophoblast differentiation. We previously observed that phorbol
      12-myristate 13-acetate (PMA) stimulates phosphorylation of GCMa on serines 328,
      378 and 383 through the protein kinase C (PKC)- and mitogen-activated protein
      kinase kinase (MEK)/extracellular signalregulated kinase (ERK)-dependent pathway,
      which decreases the protein stability of GCMa. Here we report that PMA increases
      the ubiquitination level of GCMa, dependent on the phosphorylation of GCMa on
      serines 328, 378 and 383. We found that this phosphorylation also stimulates the
      transcriptional activity of GCMa. Our data indicate that the PMA-induced PKC- and
      MEK/ERKdependent pathway enhances the degradation as well as the transcriptional
      activity of GCMa. We also examined the impact of this signaling pathway on
      trophoblasts and the results suggest that the PKC- and MEK/ERK-dependent pathway
      is involved in the regulation of trophoblast differentiation.

PMID- 22975631
TI  - Acute stress induces the modification of the lymphocyte proteins of mouse liver.
AB  - We studied the effect of acute stress on mouse immune system and found that the
      stress modified the proteins existing in the lymphocytes of liver. Performing SDS
      polyacrylamide gel electrophoresis (SDS-PAGE), we got the result that the
      proteins existing in the lymphocytes were different between stressed liver and
      non-stressed liver, whereas we could not find any detectable differences in the
      lymphocyte proteins between stressed spleen and non-stressed spleen. In stressed
      liver lymphocytes, we found thirteen clear bands in the stained gel that were not
      prominent in non-stressed liver lymphocytes.

PMID- 22975633
TI  - Immunoexpression of aquaporin-1 in the rat periodontal ligament during
      experimental tooth movement.
AB  - This study examined the immunoexpression pattern of aquaporin-1 (AQP1), first
      identified as a water channel protein, in the periodontal ligament of rat molars
      during experimental tooth movement to clarify its role in periodontal responses
      in an overloaded model by the insertion of a piece of elastic band. In the
      control group without any treatment, the cementoblasts and osteogenic cells as
      well as the vascular endothelial cells showed AQP1 immunoreaction. In the
      experimental group, hyalinized tissue and intensely AQP1 positive amorphous
      structures which were identified as degenerated endothelial cells by
      immunoelectron microscopy, occurred at the compression side on Days 1 and 3. AQP1
      immunoreaction came to be stronger in the intact endothelial cells around the
      hyalinized tissue. The hyalinized tissue had almost disappeared by Day 5 when
      many macrophages reactive to acid phosphatase activity appeared. The periodontal
      width on Day 7 became almost the same as that in the control group. These
      findings indicate that the hyalinized tissue and damaged AQP1 positive
      endothelial cells are phagocytized by macrophages which have temporally migrated,
      and suggest that the surviving endothelial cells with intense AQP1 reaction are
      involved in periodontal regeneration by capillary sprouting.

PMID- 22975634
TI  - Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in
      rats.
AB  - Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging
      to the cabbage family (Brassicaceae) that contains a large amount of health
      promoting phytochemicals. There are any reports about the effects of kale
      ingestion on the chemoprevention function and mechanism, but the interactions
      between kale and drugs have not been researched. We investigated the effects of
      kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs,
      including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for
      CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone
      (for CYP2E1). Cocktail drugs were administered into rats treated with kale and
      cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a
      significant increase in plasma levels and the AUC of midazolam, caffeine, and
      dextromethorphan. In addition, the plasma concentration and AUC of omeprazole
      tended to increase. Additionally, no almost differences in the mRNA expression
      levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion
      was considered to have an inhibitory effect on the activities of CYP3A4, 1A2,
      2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the
      mRNA expressions.

PMID- 22975635
TI  - Skin rubdown with a dry towel, 'kanpu-masatsu' is an aerobic exercise affecting
      body temperature, energy production, and the immune and autonomic nervous
      systems.
AB  - Skin rubdown using a dry towel (SRDT) to scrub the whole body is a traditional
      therapy for health promotion. To investigate its mechanism, 24 healthy male
      volunteers were studied. Body temperature, pulse rate, red blood cells (RBCs),
      serum levels of catecholamines and cortisol, blood gases (PO(2), sO(2), PCO(2)
      and pH), lactate and glucose, and the ratio and number of white blood cells
      (WBCs) were assessed before and after SRDT. After SRDT, pulse rate and body
      temperature were increased. PO(2), sO(2) and pH were also increased and there was
      no Rouleaux formation by RBCs. Lactate level tended to increase, whereas that of
      glucose did not. Adrenaline and noradrenaline levels increased, indicating
      sympathetic nerve (SN) dominance with increase in granulocytes. WBC number and
      ratio were divided into two groups according to granulocyte ratio (<= or < 60%)
      before SRDT: a normal group and a SN group. Only in the SN group did the
      granulocyte ratio decrease and the lymphocyte ratio and number increase after
      SRDT. It is suggested that SRDT is a mild aerobic, systemic exercise that might
      affect the immune system via the autonomic nervous system.

PMID- 22975636
TI  - Lymphopenia in Ednrb-deficient rat was strongly modified by genetic background.
AB  - The endothelin signaling pathway plays an important role in the migration,
      proliferation, and differentiation of neural crest cells. Mutations in the gene
      encoding the endothelin receptor type B (EDNRB) cause three symptoms:
      aganglionosis, pigmented disorder and hearing loss. In addition, the Ednrb null
      mice show abnormal splenic microarchitecture with lymphopenia. In this study, we
      examined whether similar phenotypes are reproduced in three Ednrb-null rat
      strains that we established previously. AGH-Ednrb(sl)/(sl) strain showed a low
      white blood cell count, significant size reduction and abnormal microarchitecture
      of spleen. Thymus displayed a marked reduction in the size, but maintained a
      normal CD4/CD8 ratio. In contrast, splenic cellularity was reduced to < 15%, and
      splenic B and T cell numbers were reduced, showing a splenic lymphopenia.
      Interestingly, Ednrb-null rats in the LE and F344 genetic background did not show
      these abnormalities. These data show that proper T and B cell development is
      dependent on the endothelin signaling pathway, however, modifier gene(s) might be
      differentially expressed in these strain to modulate or compensate for the effect
      of the Ednrb deficiency.

PMID- 22975637
TI  - Eight-French intracardiac echocardiography - safe and effective guidance for
      transcatheter closure in atrial septal defects -.
AB  - BACKGROUND: Intracardiac echocardiography (ICE) was introduced as a new guidance
      system for transcatheter closure of secundum atrial septal defect (ASD) with
      Amplatzer septal occluder (ASO). The aim of this study was to investigate the
      clinical outcome of ICE-guided transcatheter closure of ASD compared with the
      trans-esophageal echocardiography (TEE)-guided method. METHODS AND RESULTS: From
      May 2003 to April 2010, 560 patients who underwent transcatheter closure of ASD
      using ASO in a single institute were analyzed retrospectively. In the TEE-guided
      group (n=237), all the patients underwent general anesthesia. The median age was
      24.2 years (range, 14 months-63 years) and the average weight was 42.3 +/- 21.6
      kg (range, 8.2-82 kg). One patient underwent surgery due to migration of device.
      The remaining 236 patients underwent the procedure successfully without
      significant complication. In the ICE-guided group (n=323), the median age was
      30.5 years (range, 7 months-75 years). One patient underwent surgery because of
      mitral valve encroachment by left atrial disk after device placement. Another
      patient also underwent surgery due to device embolization. The remaining 321
      procedures were performed successfully without major complications. Procedure
      time was 104.2 min and 87.7 min, respectively (P<0.001). CONCLUSIONS: ICE-guided
      ASD occlusion with ASO is safe and effective and provides accurate anatomical
      information, sufficient to perform the procedure. In addition, there were
      benefits of avoidance of general anesthesia, and shorter procedure time. 

PMID- 22975638
TI  - Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney
      injury - a systematic review and meta-analysis -.
AB  - BACKGROUND: Sodium bicarbonate has been postulated to prevent contrast-induced
      acute kidney injury (CI-AKI) by various mechanisms, although the reports are
      conflicting. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and the Cochrane
      databases for randomized controlled trials that compared a sodium chloride with a
      sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19
      clinical trials consisting of 3,609 patients were combined. Preprocedural
      hydration with sodium bicarbonate was associated with a significant decrease in
      the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36-0.86;
      P=0.008). Stratified analyses by the type of contrast medium suggested lower odds
      of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR
      0.40; 95% CI 0.23-0.71, P=0.002) compared with those using the iso-osmolar agents
      (OR 0.76; 95% CI 0.41-1.43; P=0.40). No significant difference in the rates of
      postprocedural death (OR 0.49; 95% CI 0.23-1.04; P=0.06) and the requirement for
      renal replacement therapy (OR 0.94; 95% CI 0.46-1.91; P=0.86) was observed.
      However, we found significant changes in serum bicarbonate and potassium levels
      after sodium bicarbonate infusion. CONCLUSIONS: This updated meta-analysis
      demonstrates that sodium bicarbonate-based hydration is superior to sodium
      chloride in preventing CI-AKI of patients undergoing exposure to iodinated
      contrast media.

PMID- 22975639
TI  - Alu-based cell-free DNA: a potential complementary biomarker for diagnosis of
      colorectal cancer.
AB  - OBJECTIVES: Many patients with colorectal cancer (CRC) present with regional or
      widespread metastasis, partially reflecting limitations of the current screening
      programs. This study was aimed to find a complementary marker that can improve
      the diagnostic accuracy. DESIGN AND METHODS: Concentrations of cell-free DNA
      based on Alu (Alu-based CFD) in 31 unselected CRC patients, 30 intestinal polyp
      patients and 92 healthy individuals were detected by branch DNA (bDNA).
      Concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9
      (CA19-9) were detected by ARCHITECT assay. RESULTS: There was significant
      difference in concentrations of CFD between CRC and intestinal polyp patients or
      healthy individuals (P<0.0001). There was no statistically significant difference
      in CFD in different subgroups of CRC patients with respect to gender, age, tumor
      site and pathologic stage, suggesting that CFD might be an independent marker
      relative to CEA and CA19-9. There was a significant correlation between
      pathologic stage and CEA or CA19-9. Although no significant correlation was
      observed between pathologic stage and CFD, CFD (the area under the receiver
      operating characteristic curve (AUC)=0.904) seemed to be a better indicator to
      distinguish CRC patients from intestinal polyp patients as compared with CEA
      (AUC=0.681) or CA19-9 (AUC=0.651). CFD was more accurate than CEA or CA19-9 in
      diagnosing CRC. CONCLUSIONS: Combination of CFD, CEA and CA19-9 may be a better
      option for the diagnosis of CRC than any of them used alone. Discrimination CRC
      from intestinal polyp patients with CFD and staging with CEA and CA19-9 may
      substantially improve the accuracy CRC diagnosis.

PMID- 22975640
TI  - Combinative analysis of factors influence serum alanine aminotransferase activity
      in adult male population from southern China.
AB  - OBJECTIVES: Abnormal alanine aminotransferase (ALT) activity is indicative of
      liver disease even a burden of overall health. We assessed the factors associated
      with ALT activity and their internal relationships in a male population from
      southern China. DESIGN AND METHODS: Data of physical examinations, laboratory
      tests, hepatic ultrasounds and standardized questionnaire were collected from
      2119 males participating in a population-based survey from September 2009 to
      December 2009. RESULTS: Nonalcoholic fatty liver disease (NAFLD) and metabolic
      syndrome (MetS) were associated with the elevation of ALT levels (P<0.05).
      Prevalence of NAFLD was correlated to MetS (r=0.991, P=0.009). The levels of
      abnormal metabolic syndrome components increased in proportion with the ALT
      elevation (P<0.01). Obesity and hyperlipidemia were associated with the ALT
      levels in multivariate regression analysis (P<0.01). There was no synergic effect
      of hepatitis B virus surface antigen (HBsAg) and MetS on the ALT levels (synergy
      index [SI]=0.74, 95% confidence interval [CI]: 0.71-0.80). CONCLUSION: NAFLD and
      MetS were associated with ALT levels in a male population from southern China.
      Obesity and hyperlipidemia were independent MetS components contributing to
      elevated ALT (e-ALT). This finding might suggest necessity on justification of
      these confounding factors when detecting ALT levels among this population.

PMID- 22975641
TI  - Quantification of total hexose on dry blood spot by tandem mass spectrometry.
AB  - BACKGROUND: Because hypoglycemia and hyperglycemia are harmful and not always
      associated with overt clinical signs, it is necessary to have methods available
      to screen for glucose levels to detect hypoglycemia and diabetes as early as
      possible. A new method for such screening and the clinical determination of blood
      total hexose on a dry blood spot (DBS) using tandem mass spectrometry (MS/MS) was
      developed. METHODS: The serum glucose controls and blood were prepared as DBS and
      then extracted into a methanol solution containing isotope-labeled internal
      standards. The methanolic extraction was subjected to HPLC, followed by MS/MS in
      positive ion mode. Multiple-reaction monitoring of m/z 203.1->23 was used to
      detect hexose, and m/z 209.0->23 was used for 13C6-D-glucose. RESULTS: The
      recoveries of blood glucose by MS/MS were 90%-102% with an R(2) value of 0.999
      after linear regression (p<0.001). The controls were within an acceptable range,
      and the coefficients of variation were less than 10%. The blood total hexose in
      neonates aged 3-7 days (6.41+/-1.46 mmol/L) was lower than that in neonates aged
      8-30 days (6.66+/-1.38 mmol/L), and it was lower in neonates than in children
      aged 1-72 months (7.19+/-1.87 mmol/L). CONCLUSION: Quantification of total hexose
      on a dry blood spot by MS/MS is accurate, reliable and feasible for screening and
      clinical tests.

PMID- 22975642
TI  - Protease profiling of different biofluids in type 1 diabetes mellitus.
AB  - OBJECTIVES: We aimed to disclose the proteolytic events underlying type 1
      diabetes and related complication through protease profiling in the bodily fluids
      serum, urine and saliva. DESIGN AND METHODS: Zymography followed by LC-MS/MS was
      performed for protease identification and quantitative comparison of proteolytic
      activity between healthy, type 1 diabetic patients with no complications and with
      retinopathy and nephropathy. Western blotting was also accomplished for MMP-9 and
      MMP-2 identification and expression analysis. RESULTS: Only MMP-2 and MMP-9 were
      observed in serum with significantly increased levels and activity observed in
      diabetic patients. In urine and saliva other proteases besides MMPs were
      identified by MS and presented disease-dependent activity variations. Among these
      are complex MMP-9/Neutrophil gelatinase-associated lipocalin, aminopeptidase N,
      azurocidin and kallikrein 1 with more activity noticed in type 1 diabetes
      patients with nephropathy and/or retinopathy. CONCLUSION: Our data highlight the
      usefulness of urine and saliva for the monitoring of type-1 diabetes-related
      proteolytic events, where aminopeptidase N, azurocidin and kallikrein 1 appear as
      promising screening targets for type 1 diabetes-related complications.

PMID- 22975643
TI  - Leptin and leptin receptor genetic variants associate with habitual physical
      activity and the arm body composition response to resistance training.
AB  - PURPOSE: We investigated the influence of Leptin (LEP) and leptin receptor (LEPR)
      SNPs on habitual physical activity (PA) and body composition response to a
      unilateral, upper body resistance training (RT) program. METHODS: European
      derived American volunteers (men=111, women=131, 23.4 +/- 5.4 yr, 24.4 +/- 4.6
      kg.m(-2)) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G
      (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183).
      They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat
      volumes were measured before and after 12 wk of supervised RT with MRI.
      Multivariate and repeated measures ANCOVA tested differences among phenotypes by
      genotype and gender with age and body mass index as covariates. RESULTS: Adults
      with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA
      (1273.3 +/- 176.8, p=0.017) and sports/recreation (1922.8 +/- 226.0, p<0.04) than
      A allele carriers (718.0 +/- 147.2, 1328.6 +/- 188.2, respectively). Those with
      the LEP 19 GG genotype spent more h/wk in light intensity PA (39.7 +/- 1.6) than
      A allele carriers (35.0 +/- 1.4, p=0.03). In response to RT, adults with the LEPR
      668 G allele gained greater arm muscle volume (67,687.05 +/- 3186.7 vs. 52,321.87
      +/- 5125.05 mm(3), p=0.01) and subcutaneous fat volume (10,599.89 +/- 3683.57 vs.
      -5224.73 +/- 5923.98 mm(3), p=0.02) than adults with the LEPR 668 AA genotype,
      respectively. CONCLUSION: LEP19 G>A and LEPR 668 A>G associated with habitual PA
      and the body composition response to RT. These LEP and LEPR SNPs are located in
      coding exons likely influencing LEP and LEPR function. Further investigation is
      needed to confirm our findings and establish mechanisms for LEP and LEPR genotype
      and PA and body composition associations we observed.

PMID- 22975644
TI  - The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update
      by meta-analysis of 53 individual studies.
AB  - The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role
      in DNA repair pathways. Epidemiological studies have revealed the association
      between XRCC1 Arg280His polymorphism and cancer risk, but the results were
      inconsistent. We conducted this meta-analysis to assess the effect of XRCC1
      Arg280His polymorphism on cancer susceptibility with accumulated data. Up to
      January 2012, 53 case-control studies with 21,349 cases and 23,649 controls were
      available for our study. Summary odds ratios (OR) and corresponding 95%
      confidence intervals (CIs) for XRCC1 Arg280His polymorphism and cancer were
      estimated using fixed- or random-effects models when appropriate. Our meta
      analysis identified that elevated cancer risk was statistically associated with
      the minor variant His allele and Arg-His/His-His genotypes both in the overall
      population (allele comparison, His versus Arg: OR=1.16; 95% CI: 1.08-1.25;
      dominant comparison, Arg-His/His-His versus Arg-Arg: OR=1.17; 95% CI: 1.08-1.27)
      and in terms of subgroup analyses by ethnicity for both Caucasians and non
      Caucasians. However, no significant result was observed in the stratified
      analysis by cancer type. Moreover, significantly increased cancer risk was
      observed in smokers. These findings indicated that XRCC1 Arg280His polymorphism
      may play a role in cancer development.

PMID- 22975645
TI  - Unprotected left main coronary artery disease in patients with low predictive
      risk of mortality.
AB  - BACKGROUND: There has been an increasing use of percutaneous coronary
      intervention with drug-eluting stent (DES) in patients with unprotected left main
      coronary artery disease. We assessed whether coronary artery bypass grafting
      (CABG) would be superior to percutaneous coronary intervention with first
      generation DES in patients with unprotected left main coronary artery disease.
      METHODS: Between January 2003 and December 2007, a total of 295 patients with
      unprotected left main coronary artery disease were treated with Kurashiki Central
      Hospital, Okayama, Japan. Among these patients, 169 and 126 underwent CABG and
      percutaneous coronary intervention with DES, respectively. The average Society of
      Thoracic Surgeons' predictive risk of mortality score was 2.3+/-3.8%. We defined
      higher-risk and lower-risk patients as those with Society of Thoracic Surgeons'
      predictive risk of mortality scores higher than 2.3% (CABG, n=48; percutaneous
      coronary intervention, n=28) and lower than 2.3% (CABG, n=121; percutaneous
      coronary intervention, n=98), respectively. Survival, major adverse cardiac
      related events, and target lesion revascularization were analyzed by the Kaplan
      Meier method. RESULTS: Between-group differences in favor of CABG were seen with
      respect to the rate of major adverse cardiac-related events and target lesion
      revascularization in both strata. In patients with lower scores according to the
      Society of Thoracic Surgeons' predictive risk of mortality, the cardiac death
      free survival rate was significantly higher in CABG. CONCLUSIONS: In this 5-year
      single-center experience, CABG is recommended for unprotected left main coronary
      artery disease, especially in patients with low scores in the Society of Thoracic
      Surgeons' predictive risk of mortality.

PMID- 22975646
TI  - Learning curve of laparoscopy spleen-preserving splenic hilar lymph node
      dissection for advanced upper gastric cancer.
AB  - BACKGROUND/AIMS: To investigate the learning curve of laparoscopy spleen
      preserving splenic hilar lymph node dissection for advanced upper gastric cancer
      (AUGC). METHODOLOGY: A retrospective analysis of clinical data of 100 cases of
      spleen-preserving splenic hilar lymph node dissection for AUGC, completed by the
      same group of physicians with extensive laparoscopic gastric cancer surgical
      experience. The patients were divided into five groups (A, B, C, D and E) in
      accordance with their surgical priorities. RESULTS: The five groups of patients
      were comparable in age, gender, body mass index, spleen lobe artery count,
      histological type and invasion department. The surgical time for Group A and
      Group B was longer than Group C, Group D and Group E. The amount of bleeding for
      Group A and Group B was significantly larger than Group C, Group D and Group E.
      Laparotomy rate, the number of splenic hilar lymph node dissection, incidence of
      complications, recovery time of bowel function, days for postoperative hospital
      stay were not statistically different among the five groups. CONCLUSIONS: On the
      basis of skilled surgical techniques for laparoscopic gastric cancer, the
      learning curve for laparoscopy spleen-preserving splenic hilar lymph node
      dissection for upper advanced gastric cancer was roughly 40 cases.

PMID- 22975648
TI  - Prognostic value of postoperative CA19-9 normalization in patients with advanced
      gastric cancer.
AB  - BACKGROUND/AIMS: CA19-9 is known to have positive correlation with depth of
      invasion, nodal involvement, and peritoneal metastasis in gastric adenocarcinoma.
      In patients with high preoperative CA19-9 serum levels who underwent curative
      gastrectomy, we evaluated the prognostic impact of postoperative normalization of
      CA 19-9. METHODOLOGY: Among 1,439 patients who underwent curative gastrectomy for
      advanced gastric adenocarcinoma, data of 102 patients with advanced gastric
      adenocarcinoma whose preoperative serum CA19-9 level was higher than cutoff value
      (37 U/mL) were reviewed. If serum CA19-9 level had fallen below 37 U/mL at 6
      months after surgery, the CA19-9 level was considered normalized. RESULTS: CA19-9
      levels were normalized in 79 patients but not in 23 patients. There were
      statistically significant differences in prognosis according to depth of
      invasion, presence of lymph node metastasis, extent of gastric resection, and
      postoperative CA19-9 normalization on univariate analyses. Multivariate analysis
      revealed that pathological lymph node metastasis (p<0.001) and postoperative CA19
      9 normalization were independent prognostic factors (p=0.001). CONCLUSIONS: In
      patients with advanced gastric adenocarcinoma who underwent curative gastric
      resection, postoperative normalization of CA19-9 can be a surrogate for
      potentially curative surgical treatment and can be used as a good prognostic
      factor.

PMID- 22975649
TI  - Multi-center study regarding the risk factors for bleeding in gastrointestinal
      stromal tumor.
AB  - BACKGROUNDS/AIMS: In spite of several case reports about gastrointestinal stromal
      tumor (GIST) complicated with hemorrhage, study regarding the risk factors of
      bleeding in this tumor is scanty. Therefore, we analyzed the clinical
      characteristics of bled GISTs and tried to find risk factors of bleeding by
      comparing with non-bled cases. METHODOLOGY: Medical records of 49 bled GIST cases
      from 5 university hospitals in Korea between year 2001 to 2010 were compared with
      96 non-bled cases. Whole pathological slides were reviewed by an experienced
      pathologist. RESULTS: Female predominance (58.6%) was noted and the mean age of
      the included patients was 58.4+/-13.1 years. In univariate analysis, location of
      jejunum, prolonged prothrombin time, presence of surface dimpling in CT, cellular
      pleomorphism and positivity of S100 was significantly dominant in the bled cases.
      Multivariate analysis showed significant differences in the location of jejunum
      (p=0.004, OR=3.533), prolonged prothrombin time (p=0003, OR=19.643), presence of
      surface dimpling (p=0.026, OR=6.250) in CT, and positivity of S100 (p=0.001,
      OR=12.941). CONCLUSIONS: Location of jejunum, prolonged prothrombin time,
      presence of surface dimpling in CT, and positivity of S100 are independent risk
      factors associated with bleeding in GI GIST patients.

PMID- 22975650
TI  - Significance of surgical treatment in multimodal therapy for stage IV highly
      advanced gastric cancer.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the efficacy of
      surgical treatment following a response to chemotherapy to improve stage IV
      gastric cancer and to identify the factors contributing to survival benefit.
      METHODOLOGY: In total, 148 patients with cStage IV gastric cancer were treated
      with S-1 and CDDP. We retrospectively evaluated the factors contributing to a
      survival benefit and the significance of surgical treatment. RESULTS: The 148
      cStage IV patients included 107 males with a median age of 61 years. The overall
      response rate was 54.7%. After chemotherapy, 97 patients underwent surgery. R0
      resection was successfully performed in 51 (52.6%) patients. The overall median
      survival time (MST) of the patients was 16.8 months, with a 5YSR of 16.4%. The
      MST of patients who went on to receive surgery was 22.5 months, and the 5YSR was
      19.6%. In the multivariate analysis of 97 patients who underwent surgery, R0
      resection, lymph node dissection of D2/D3 and obtaining a CR/PR from chemotherapy
      were the only independently prognostic factors. CONCLUSIONS: The use of multi
      modal treatment, including surgical treatment, at an appropriate time was well
      tolerated and effective for patients with stage IV gastric cancer.

PMID- 22975651
TI  - Preoperative drainage for distal biliary obstruction: endoscopic stenting or
      nasobiliary drainage?
AB  - BACKGROUND/AIMS: Few studies have compared endoscopic biliary stenting and
      endoscopic nasobiliary drainage for preoperative biliary drainage in patients
      with malignant distal biliary obstruction. We aimed to evaluate their safety and
      efficacy in such patients awaiting pancreaticoduodenectomy. METHODOLOGY: Seventy
      six of 80 patients (40 with pancreatic cancer, 26 with distal bile duct cancer,
      and 14 with ampullary cancer) who underwent endoscopic preoperative biliary
      drainage were included, and we evaluated whether endoscopic biliary stenting or
      endoscopic nasobiliary drainage provided a safer and more effective drainage for
      patients awaiting pancreaticoduodenectomy. We also determined whether the type of
      cancer influenced tube dysfunction. RESULTS: No significant differences in the
      overall rate of catheter-related complications, the rate of tube dysfunction, or
      the median interval from preoperative biliary drainage to the time of tube
      dysfunction were observed between the two groups. Tube dysfunction was observed
      significantly more frequently in patients with pancreatic cancer than in those
      with distal bile duct or ampullary cancer. CONCLUSIONS: Both endoscopic biliary
      stenting and endoscopic nasobiliary drainage provided safe and effective drainage
      for patients awaiting pancreaticoduodenectomy. Tube dysfunction was associated
      with preoperative biliary drainage significantly earlier in patients with
      pancreatic cancer than in those with distal bile duct cancer or ampullary cancer.

PMID- 22975652
TI  - Radiation-induced impacts on the degradation of 2,4-D and the microbial
      population in soil microcosms.
AB  - In a soil microcosm experiment, the influence of low-level (137)Cs and (90)Sr
      contamination on the degradation of (14)C-ring-labeled 2,4-dichlorophenoxyacetic
      acid (2,4-D) was studied. Two differently treated soils (one native soil and one
      soil sterilized and reinoculated with a biotic soil aliquot) were artificially
      contaminated with various concentrations of (137)Cs and (90)Sr as nitrate salts.
      The cumulative doses increased up to 4 Gy for 30 days of incubation in soil
      microcosms. Changes in microbial community structure were observed with help of
      the denaturing gradient gel electrophoresis (DGGE). A radiation-induced impact
      appeared only in the microcosms treated with 30 times the maximum contamination
      appearing in the exclusion zone around reactor 4 in Chernobyl. In contrast to the
      less contaminated soils, the mineralization of 2,4-D was delayed for 4 days
      before it recovered. Slight shifts in the microbial communities could be traced
      to radiation effects. However, other parameters had a major impact on
      mineralization and community structure. Thus the sterilization and reinoculation
      and, of course, application of the 2,4-D were predominantly reflected in the
      (14)CO(2) emissions and the DGGE gel patterns.

PMID- 22975653
TI  - Management of Rhodotorula scleritis.

PMID- 22975654
TI  - Botulinum toxin to improve lower facial symmetry in facial nerve palsy.
AB  - INTRODUCTION: In long-standing facial palsy, muscles on the normal side
      overcontract causing difficulty in articulation, eating, drinking, cosmetic
      embarrassment, and psychological effects as patients lack confidence in public.
      METHODS: We injected botulinum toxin A (BTXA) into the normal contralateral smile
      muscles to weaken them and restore symmetry to both active and passive movements
      by neutralising these overacting muscles. RESULTS: A total of 14 patients
      received BTXA (79% women, median age 47 years, average length of palsy 8 years).
      They were all difficult cases graded between 2 and 6 (average grade 3 House
      Brackmann). All 14 patients reported improved facial symmetry with BTXA (dose
      altered in some to achieve maximum benefit). Average dose was 30 units, but
      varied from 10 to 80 units. Average time to peak effect was 6 days; average
      duration of effect was 11 weeks. Three patients had increased drooling (resolved
      within a few days). CONCLUSION: The improvement in symmetry was observed by both
      patient and examining doctor. Patients commented on increased confidence, being
      more likely to allow photographs taken of themselves, and families reported
      improved legibility of speech. Younger patients have more muscle tone than older
      patients; the effect is more noticeable and the benefit greater for them. BTXA
      improves symmetry in patients with facial palsy, is simple and acceptable, and
      provides approximately 4 months of benefit. The site of injection depends on the
      dynamics of the muscles in each individual patient.

PMID- 22975655
TI  - Patient-reported benefit from oculoplastic surgery.
AB  - PURPOSE: It is vital that surgeons undertaking oculoplastic procedures are able
      to show that the surgery they perform is of benefit to their patients. Not only
      is this fundamental to patient-centred medicine but it is also important in
      demonstrating cost effectiveness. There are several ways in which benefit can be
      measured, including clinical scales, functional ability scales, and global
      quality-of-life scales. The Glasgow benefit inventory (GBI) is an example of a
      patient-reported, questionnaire-based, post-interventional quality-of-life scale
      that can be used to compare a range of different treatments for a variety of
      conditions. METHODS: A cross-sectional study was undertaken using the GBI to
      score patient benefit from four commonly performed oculoplastic procedures. It
      was completed for 66 entropion repairs, 50 ptosis repairs, 41 ectropion repairs,
      and 41 external dacryocystorhinostomies (DCR). The GBI generates a scale from 
      100 (maximal detriment) through zero (no change) to +100 (maximal benefit).
      RESULTS: The total GBI scores of patients undergoing surgery for entropion,
      ptosis, ectropion, and external DCR were: +25.25 (95% CI 20.00-30.50, P<0.001),
      +24.89 (95% CI 20.04-29.73, P<0.001), +17.68 (95% CI 9.46-25.91, P<0.001), and
      +32.25 (95% CI 21.47-43.03, P<0.001), respectively, demonstrating a statistically
      significant benefit from all procedures. CONCLUSION: Patients derived significant
      quality-of-life benefits from the four most commonly performed oculoplastic
      procedures.

PMID- 22975656
TI  - Comparative evaluation of lymphatic vessels in primary versus recurrent
      pterygium.
AB  - PURPOSE: To compare lymphangiogenesis in primary versus recurrent pterygium.
      METHODS: Tissues from 88 excised primary and 34 recurrent pterygia were
      evaluated, and tissues from 7 nasal epibulbar conjunctivae segments were used as
      controls. The lymph-vascular area (LVA), lymph-microvascular density (LMD), and
      lymph-vascular luminal diameter (LVL) were examined and compared between the
      primary and recurrent pterygia. In addition, the expression of VEGF-A and VEGF-C
      in the primary and recurrent pterygia were determined by ELISA and real-time PCR.
      The relationships between the mRNA level and LVA, LMD, and LVL were clarified.
      RESULTS: Although there was no significant difference in quantification of LVL
      between primary and recurrent pterygia, the quantification of LVA and LMD in
      recurrent pterygia dramatically increased in comparison with primary pterygia
      (both P-values <0.01). Compared with primary pterygia, the VEGF-A and VEGF-C mRNA
      levels were up-regulated significantly in recurrent pterygia (both P-values
      <0.05). There was a significant relationship between VEGF-C mRNA and LVA, LMD,
      and LVL, while VEGF-A mRNA was only closely correlated with LMD in recurrent
      pterygia. CONCLUSIONS: Lymphangiogenesis develops in recurrent pterygium, for
      which transient up-regulation of VEGF-C might be responsible.

PMID- 22975657
TI  - Eye preservation tectonic graft using glycerol-preserved donor cornea.
AB  - AIMS: To report the surgical outcome of tectonic graft using glycerol-preserved
      donor corneas to treat perforated keratitis. METHODS: The medical records were
      reviewed of all patients treated for perforated keratitis using glycerol
      preserved corneas at a single institution between 1 July 2004 and 31 June 2010.
      The clinical features, precipitating factors, adjuvant therapies, and therapeutic
      outcomes were analyzed. Success was defined as re-epithelialization of the ocular
      surface without evisceration. RESULTS: Fourteen eyes from 14 patients (6 male and
      8 female) were included. Age ranged from 58 to 84 years (average, 70.71 +/- 8.52
      years) and the follow-up time ranged from 7 to 56 months (mean, 25.35 +/- 16.84
      months). The culture results showed five bacterial infections, five cases of
      fungal keratitis, and one mixed infection; the culture results were negative for
      three patients. Satisfactory anatomical integrity was obtained in eight grafts
      (57.14%) that healed with neovascularization. Six grafts (48.85%) showed delayed
      re-epithelialization and were repaired with conjunctival flaps to maintain ocular
      surface integrity. Three patients developed secondary glaucoma and received trans
      scleral cyclophotocoagulation. Thirteen patients had satisfactory anatomical
      integrity without evisceration or exenteration, while one patient received
      evisceration at 39-month follow-up because of intractable glaucoma. CONCLUSIONS:
      Glycerol-preserved donor corneas combined with anterior vitrectomy with or
      without conjunctival flaps may be effective substitutes for evisceration surgery
      in patients with perforated keratitis.

PMID- 22975658
TI  - Differences in central corneal thickness between the paired eyes and the severity
      of the glaucomatous damage.
AB  - PURPOSE: To evaluate whether a difference in central corneal thickness (CCT)
      between the paired eyes could be associated to worse glaucoma in the thinner
      cornea eye. METHODS: From 16 different glaucoma centres, at least 50 glaucomatous
      patients were saved on the Italian Glaucoma Register. Eight hundred and sixteen
      glaucomatous patients were found in the register. CCT, ophthalmoscopic cup/disc
      ratio, mean deviation (MD), pattern SD (PSD), and intraocular pressure (IOP). The
      difference (Delta) between the paired eyes was calculated for all the considered
      parameters and two subgroups were created on the basis of DeltaCCT. Because the
      difference between the two eyes could be positive or negative, the absolute value
      of Delta was considered for all the measurements. Three different DeltaCCT
      cutoffs were selected: 10, 15, and 20 MUm. Student's t-test was used to compare
      the subgroups. RESULTS: When the entire group was divided in two subgroups using
      20 MUm as DeltaCCT cutoff, no significant difference was found for DeltaIOP (
      0.38 +/- 2.53 (mean +/- SD) mm Hg and -0.07 +/- 2.35 mm Hg, respectively) between
      the two subgroups. Significant (P<0.001) difference was found for DeltaMD (6.58
      +/- 7.30 and 3.14 +/- 4.22 dB, respectively), DeltaPSD (3.92 +/- 4.01 and 2.16 +/
      2.57, respectively), and DeltaC/D (0.11 +/- 0.14 and 0.08 +/- 0.11,
      respectively) between the two subgroups. No significant correlation was found
      between DeltaCCT and the other parameters. CONCLUSION: The DeltaCCT between the
      two eyes could be associated to a worse glaucoma in the thinner cornea eye.

PMID- 22975659
TI  - Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the
      natriuretic peptide system and TNF-alpha.
AB  - Cardiovascular and immune system abnormalities have been reported in females with
      estrogen deficiency. To control these disorders in post-menopausal women, hormone
      replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the
      effects of tibolone on the natriuretic peptide system have not been determined.
      We investigated the effects of tibolone on the natriuretic peptide system and pro
      inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided
      into four groups: SHAM, OVX, OVX treated with 17beta-estradiol (OVX+E: 14 days)
      and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after
      ovariectomy. On day 35, blood was collected to determine atrial natriuretic
      peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)
      levels. In addition, tissues were collected for determining ANP, natriuretic
      peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by
      RT-PCR. The cytokine levels of both IL-6 and TNF-alpha were increased in OVX
      animals. In comparison, IL-6 and TNF-alpha levels were reduced in OVX+E animals.
      TNF-alpha levels were reduced similarly in OVX+T animals, but IL-6 levels
      remained elevated in this group. The concentrations of ANP in the left atrium
      tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in
      the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene
      expression in the kidney tissue was observed among the groups. Tibolone and
      17beta-estradiol effectively increased plasma ANP and ANP mRNA levels in the left
      atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone
      normalizes plasma ANP and serum TNF-alpha levels our results suggest that
      treatment with tibolone has anti-inflammatory effects and could prevent
      cardiovascular disease in the long-term.

PMID- 22975660
TI  - The permanent improvement of proteinuria and renal failure with colchicine and
      enalapril in a leukemic patient with renal amyloidosis secondary to ankylosing
      spondylitis: a review of the literature.
AB  - Acute leukemia has been reported as secondary to radiation therapy in patients
      with ankylosing spondylitis (AS). AA amyloidosis secondary to AS causes
      progressive organ failure. Although new therapeutic choices can be used, response
      to therapy in secondary amyloidosis is not good enough. In AA amyloidosis,
      clinical symptoms partially regress with colchicine. Here, we report a patient
      with acute leukemia and AS. After complete remission of acute leukemia, pulmonary
      tuberculosis, acute renal failure and nephrotic syndrome developed. After
      treatment of leukemia and tuberculosis, Colchicine and enalapril therapy resulted
      in an improvement of clinical symptoms. He was followed up for >15 years and is
      doing very well and has minimal symptoms related to AS. 

PMID- 22975661
TI  - Acute care medicine: perioperative management of adult congenital heart disease.
AB  - Since the advent of neonatal cardiac surgery in the 1970s, an increasing number
      of patients suffering from congenital heart disease (CHD) have survived into
      adulthood. In 2010, it is estimated that 1.2 million or 1 in 150 of young adults
      have some form of CHD in the United States. Current birth, incidence, and
      survival rate predict an increase in the CHD population between 10,000 and
      300,000 patients per year. Data from large adult CHD (ACHD) centers (UCLA,
      Toronto, Mayo Clinic) show that as many as 50% of these patients with complex
      physiology are 40 years of age or older and that two-thirds of them can be
      categorized as medium or high risk to demonstrate signs and symptoms of low
      cardiac output. As this population ages, it is very likely for hospital-based
      physicians to encounter such patients in their procedural and/or surgical
      practice. Risk stratification and interdisciplinary approach in the care of these
      patients will assure a safe outcome. The assessment of the patient must consider
      the variable expression of CHD. Because most lesions are "fixed but not cured,"
      the periprocedural practitioner must consider the altered physiology of the heart
      in context of the physiological challenges of percutaneous and open surgical
      interventions. The 2008 American Heart Association/American College of Cardiology
      guidelines for the Management of Adults with CHD establish for the first time a
      streamlined approach to the care of these patients. This review will apply these
      guidelines to the patients with ACHD undergoing noncardiac surgery and
      intervention. 

PMID- 22975662
TI  - Azilsartan, aliskiren, and combination antihypertensives utilizing renin
      angiotensin-aldosterone system antagonists.
AB  - Health care providers managing hypertension (HTN) have a large selection of
      pharmacologic agents to choose from, including several different classes of drugs
      and many similar drugs within each class. Antagonism of the renin-angiotensin
      aldosterone system has been shown to be very effective for HTN, especially in
      patients with cardiovascular disease, diabetes, and heart failure. Within this
      group, there have been 2 new agents recently introduced to the US market and
      approved by the Food and Drug Administration. It is important for the HTN
      specialist to be familiar with the merits of these 2 drugs: the angiotensin
      receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna
      (aliskiren). Additionally, there have been several new, fixed-dose combination
      antihypertensives introduced to the market since 2006 that use a renin
      angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a
      single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge
      (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta
      (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)],
      Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug
      combination medications have also been introduced recently: Exforge HCT
      (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and
      Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize
      the trial data and important pharmacologic merits of these 2 new renin
      angiotensin-aldosterone antagonists and the advantages of initiating treatment
      with one of the new fixed-dose, combination drugs approved over the last 5 years.

PMID- 22975663
TI  - A study of elderly patients with limited-stage small-cell lung cancer after
      combined chemoradiotherapy.
AB  - In this study, we evaluated the effect of chemotherapy (CT) and thoracic
      radiotherapy (RT) integration and the timing of RT on survival of elderly
      patients with limited-stage small-cell lung cancer. Eighty patients were
      retrospectively analyzed. All the patients revived thoracic RT and 70 patients
      received >=2 cycles of CT. Twenty-two patients received RT sequentially to CT, 19
      with RT consolidated with CT, and 29 with RT concurrent with CT. Early chest
      irradiation was defined as beginning RT after 1-3 cycles of CT (n = 44), and late
      chest irradiation was defined as occurring after >=4 cycles of CT (n = 26).
      Twenty-six patients (32.5%) achieved complete response, 37 (46.2%) partial
      response, 10 (12.5%) stable disease, and 7 (8.7%) progressive disease. The median
      survival time for all patients was 19 months. The 1-, 2-, and 3-year overall
      survival (OS) rates were 68.9%, 41.3%, and 31.7%, respectively. In univariate
      analyses, the volume of the primary tumor, CT, treatment modality, timing of RT,
      target volume, and RT dose were significantly associated with OS. At 3 years,
      concomitant chemoradiotherapy was superior to consolidated and sequential
      chemoradiotherapy (40.0% vs. 36.9% vs. 40.0%, respectively). The rate of OS at 3
      years was 37.1% for patients receiving early-RT and 27.8% for those receiving
      late-RT (P = 0.006). Multivariate analysis showed that CT and RT dose were
      independent factors influencing OS. Concurrent chemoradiotherapy resulted in a
      high survival rate. A radiation dose-response relationship was observed, and a
      dose of at least 60-Gy daily radiation demonstrated improved survival.

PMID- 22975664
TI  - Efficacy of cilostazol in patients with acute coronary syndrome after
      percutaneous coronary intervention.
AB  - The objective of this study was to explore the long-term effect of cilostazol
      optimized antiplatelet therapy after percutaneous coronary intervention (PCI) in
      patients with acute coronary syndrome (ACS). One hundred forty-six patients with
      ACS who underwent PCI were enrolled. Patients were randomly divided into 2 groups
      based on clot rate (CR), and both groups received antiplatelet therapy: aspirin
      and clopidogrel plus cilostazol (intensification group, n = 72) or aspirin and
      clopidogrel (control group, n = 74). Clinical follow-up was up to 12 months after
      PCI. During follow-up, CR was determined at day 1 and at 1, 3, 6, and 12 months
      post-PCI. Efficacy endpoints included second acute myocardial infarction, in
      stent thrombosis, revascularization (second PCI), sudden death, and hemorrhage.
      CR was significantly lower in the intensification group than in the control group
      at 1, 3, and 6 months after PCI (P < 0.05). The incidences of second acute
      myocardial infarction, in-stent thrombosis, revascularization (second PCI), and
      sudden cardiac death were also lower but insignificant; there were no hemorrhage
      events (P > 0.05). Cilostazol-optimized antiplatelet therapy can significantly
      decrease CR after PCI in patients with acute coronary syndrome.

PMID- 22975666
TI  - Trends in the disproportionate burden of work-related traumatic injuries
      sustained by Latinos.
AB  - OBJECTIVE: Disproportionate occupational injury rates for Latinos are well
      documented, but there is limited information about whether disparity is
      increasing over time. This study describes trends in the burden of work-related
      traumatic injuries sustained by Latinos in Washington State. METHODS: Washington
      State Trauma Registry data from 1998 to 2008 were used to model annual change in
      the odds that a work-related traumatic injury was sustained by a Latino,
      controlling for demographics, injury-related factors, and Latino representation
      in the underlying labor force. RESULTS: We found a 5% mean annual increase in the
      odds that a comparable work-related traumatic injury was sustained by a Latino (P
      = 0.007). Falls in industrial/mine/quarry locations were the strongest
      contributor to increasing disparity. CONCLUSIONS: Latinos bear an increasingly
      disproportionate burden of occupational injuries and are less likely to have
      health insurance coverage aside from workers' compensation.

PMID- 22975667
TI  - Neighborhood walkability and walking behavior: the moderating role of action
      orientation.
AB  - BACKGROUND: In promoting physical activity, it is important to gain insight into
      environmental factors that facilitate or hinder physical activity and factors
      that may influence this environment-behavior relationship. As the personality
      factor of action orientation reflects an individual's capacity to regulate
      behavior it may act as a moderator in the environment-behavior relationship. The
      current study addressed the relationship between neighborhood walkability and
      walking behavior and the influence of action orientation on this relationship.
      METHODS: Three hundred and forty-seven Dutch inhabitants [mean age 43.1 (SD
      17.1)] completed a web based questionnaire assessing demographic variables,
      neighborhood walkability (Neighborhood Environment Walkability Scale), variables
      of the Theory of Planned Behavior, action orientation, and walking behavior.
      RESULTS: The results show that high levels of neighborhood walkability are
      positively associated with walking behavior and that this influence is largely
      unmediated by cognitive processes. A positive influence of neighborhood
      walkability on walking behavior was identified in the action-oriented
      subpopulation, whereas in the state-oriented part of the population, this
      influence was absent. CONCLUSIONS: The findings suggest that the influence of
      neighborhood environment on walking behavior has a relatively large unconscious,
      automatic component. In addition, the results suggest that the walkability
      walking relationship is moderated by action orientation.

PMID- 22975665
TI  - Neurologic symptoms associated with cattle farming in the agricultural health
      study.
AB  - OBJECTIVE: Infection with Campylobacter jejuni, a bacterium carried by poultry
      and livestock, is the most frequently identified antecedent to the autoimmune
      neurologic condition Guillain-Barre Syndrome. We used Agricultural Health Study
      data to assess whether cattle farming was associated with prevalence of
      neurologic symptoms. METHODS: Prevalence of self-reported symptoms in cattle
      farmers (n = 8878) was compared with farmers who did not work with animals (n =
      7462), using multivariate regression. RESULTS: Prevalence of numbness and
      weakness were increased for beef and dairy farmers compared with the reference
      group (P < 0.0001). Of cattle farmers, 48% did not report raising other animal
      species, and prevalence of numbness and weakness were also increased in this
      subgroup compared with the reference group (P < 0.02). CONCLUSIONS: Occupational
      exposure to cattle was associated with increased prevalence of self-reported
      symptoms associated with peripheral neuropathy.

PMID- 22975668
TI  - New treatments for CKD--new insights into pathogenesis.

PMID- 22975669
TI  - Connecting the segments.

PMID- 22975670
TI  - Partial answers from partial Klotho deficiency.

PMID- 22975671
TI  - How benign is IgA nephropathy with minimal proteinuria?

PMID- 22975672
TI  - 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy
      of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Practice Guidelines.

PMID- 22975673
TI  - Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle.
AB  - We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis
      C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry
      site (IRES)-mediated translation of the viral genome. Here, we investigate the
      mechanisms of antiviral activity of quercetin and six additional bioflavonoids.
      We demonstrate that catechin, naringenin, and quercetin possess significant
      antiviral activity, with no associated cytotoxicity. Infectious virion secretion
      was not significantly altered by these bioflavonoids. Catechin and naringenin
      demonstrated stronger inhibition of infectious virion assembly compared to
      quercetin. Quercetin markedly blocked viral translation whereas catechin and
      naringenin demonstrated mild activity. Similarly quercetin completely blocked
      NS5A-augmented IRES-mediated translation in an IRES reporter assay, whereas
      catechin and naringenin had only a mild effect. Moreover, quercetin
      differentially inhibited HSP70 induction compared to catechin and naringenin.
      Thus, the antiviral activity of these bioflavonoids is mediated through different
      mechanisms. Therefore combination of these bioflavonoids may act synergistically
      against HCV.

PMID- 22975674
TI  - Expression of porcine endogenous retroviruses (PERV) in different organs of a
      pig.
AB  - Porcine endogenous retroviruses (PERVs) represent a particular risk for
      xenotransplantation using pig cells, tissues or organs. PERVs are integrated in
      the genome of all pig strains and can be released as particles that infect human
      cells. We performed for the first time a systematic analysis of PERV expression
      in different organs of a miniature pig using in parallel quantitative real-time
      RT-PCR, Western blot analysis, and immunohistochemistry. All three types of PERV,
      PERV-A, PERV-B and PERV-C were present in the germ line of the animal. In
      addition, recombinant PERV-A/C were detected in some tissues, but not in the germ
      line. Expression of the viral full-length and spliced mRNA and proteins was found
      in many organs, but at different levels. A high expression was found in lymphoid
      organs.

PMID- 22975675
TI  - PTM-driven differential peptide display: survey of peptides containing
      inter/intra-molecular disulfide bridges in frog venoms.
AB  - Amphibian defensive skin secretions are complex species-specific mixtures of
      biologically active molecules, including many uncharacterized peptides. Many of
      these peptides are post-translationally modified and amongst the modifications
      discovered so far on amphibian defense peptides, disulfide bonds are quite
      frequently encountered. The presence of this PTM often complicates the MS-based
      sequencing. Here we demonstrate a method to target peptides containing
      inter/intra-molecular S-S bonds applying a PTM-driven differential display. Upon
      reduction of the disulfide bond both molecular mass and retention time of a
      peptide are altered. Assembling the LC-MS data by plotting the m/z data against
      retention time generates a peptide display and overlaying peptide displays of
      untreated and DTT-reduced material yields a differential display. From such an
      overlay, peptides originally carrying a disulfide bond are recognized due to the
      shift in both retention time and m/z values, whereas non cystine containing
      peptides remain unaltered in the differential display. The success of this
      approach is demonstrated by the visualization of the cystines-containing peptides
      in the skin secretion of Odorrana schmackeri, Phyllomedusa burmeisteri,
      Phyllomedusa rohdei, Kassina senegalensis, and Bombina variegata. The venoms from
      these different species yield complicated differential displays, showing
      interesting peptides, allowing one to target them for more detailed structural
      characterization.

PMID- 22975676
TI  - Identification of proteins containing redox-sensitive thiols after PRDX1, PRDX3
      and GCLC silencing and/or glucose oxidase treatment in Hepa 1-6 cells.
AB  - The oxidation and reduction of cysteine thiols are thought to be a major
      mechanism for redox regulation. The aim of this study was to identify proteins
      with reactive thiols and determine their oxidation profiles under oxidative
      stress induced by simultaneous silencing of antioxidant defences (peroxiredoxin
      1, peroxiredoxin-3, and the catalytic subunit of the glutamate-cysteine ligase),
      and/or treatment with glucose oxidase (GO). Using an approach that combined the
      labelling of reversibly oxidised cysteines, 2-DE protein separation and MS
      analysis, we identified 26 proteins with cysteines prone to reversible oxidation
      belonging to different functional classes. Among these proteins are those that
      have not been previously recognised as reversible oxidation targets, including
      cytoplasmic aspartate aminotransferase, proteasome subunit alpha type-6,
      heterogeneous nuclear ribonucleoproteins isoA2/B1 and A/B, and histidine triad
      nucleotide-binding protein 1. We provide the first evidence of reversible
      oxidation for specific cysteines, including Cys112 and Cys146 in glutamate
      dehydrogenase 1, Cys17 in actins, Cys5 in protein disulfide-isomerase A3, and
      Cys267 in the heat shock cognate 71 kDa protein. Silencing induced lower
      oxidative stress than GO treatment. Nevertheless, we detected some proteins
      particularly sensitive to oxidation by silencing. We hypothesised that these
      proteins may play a role in regulatory mechanisms by redox stress.

PMID- 22975677
TI  - Cell-based and in vivo spectral analysis of fluorescent proteins for multiphoton
      microscopy.
AB  - Multiphoton microscopy of cells and subcellular structures labeled with
      fluorescent proteins is the state-of-the-art technology for longitudinal imaging
      studies in tissues and living animals. Successful analysis of separate cell
      populations or signaling events by intravital microscopy requires optimal pairing
      of multiphoton excitation wavelengths with spectrally distinct fluorescent
      proteins. While prior studies have analyzed two photon absorption properties of
      isolated fluorescent proteins, there is limited information about two photon
      excitation and fluorescence emission profiles of fluorescent proteins expressed
      in living cells and intact tissues. Multiphoton microscopy was used to analyze
      fluorescence outputs of multiple blue, green, and red fluorescent proteins in
      cultured cells and orthotopic tumor xenografts of human breast cancer cells. It
      is shown that commonly used orange and red fluorescent proteins are excited
      efficiently by 750 to 760 nm laser light in living cells, enabling dual color
      imaging studies with blue or cyan proteins without changing excitation
      wavelength. It is also shown that small incremental changes in excitation
      wavelength significantly affect emission intensities from fluorescent proteins,
      which can be used to optimize multi-color imaging using a single laser
      wavelength. These data will direct optimal selection of fluorescent proteins for
      multispectral two photon microscopy.

PMID- 22975678
TI  - Evaluation of cerebral ischemia using near-infrared spectroscopy with oxygen
      inhalation.
AB  - Conventional methods presently used to evaluate cerebral hemodynamics are
      invasive, require physical restraint, and employ equipment that is not easily
      transportable. Therefore, it is difficult to take repeated measurements at the
      patient's bedside. An alternative method to evaluate cerebral hemodynamics was
      developed using near-infrared spectroscopy (NIRS) with oxygen inhalation. The
      bilateral fronto-temporal areas of 30 normal volunteers and 33 patients with
      cerebral ischemia were evaluated with the NIRS system. The subjects inhaled
      oxygen through a mask for 2 min at a flow rate of 8  L/min. Principal component
      analysis (PCA) was applied to the data, and a topogram was drawn using the
      calculated weights. NIRS findings were compared with those of single-photon
      emission computed tomography (SPECT). In normal volunteers, no laterality of the
      PCA weights was observed in 25 of 30 cases (83%). In patients with cerebral
      ischemia, PCA weights in ischemic regions were lower than in normal regions. In
      28 of 33 patients (85%) with cerebral ischemia, NIRS findings agreed with those
      of SPECT. The results suggest that transmission of the changes in systemic SpO2
      were attenuated in ischemic regions. The method discussed here should be
      clinically useful because it can be used to measure cerebral ischemia easily,
      repeatedly, and noninvasively.

PMID- 22975679
TI  - Nondestructive fluorescence-based quantification of threose-induced collagen
      cross-linking in bovine articular cartilage.
AB  - Extensive collagen cross-linking affects the mechanical competence of articular
      cartilage: it can make the cartilage stiffer and more brittle. The concentrations
      of the best known cross-links, pyridinoline and pentosidine, can be accurately
      determined by destructive high-performance liquid chromatography (HPLC). We
      explore a nondestructive evaluation of cross-linking by using the intrinsic
      fluorescence of the intact cartilage. Articular cartilage samples from bovine
      knee joints were incubated in threose solution for 40 and 100 h to increase the
      collagen cross-linking. Control samples without threose were also prepared.
      Excitation-emission matrices at wavelengths of 220 to 950 nm were acquired from
      the samples, and the pentosidine and pyridinoline cross-links and the collagen
      concentrations were determined using HPLC. After the threose treatment,
      pentosidine and lysyl pyridinole (LP) concentrations increased. The intrinsic
      fluorescence, excited below 350 nm, decreased and was related to pentosidine [r =
      -0.90, 240/325  nm (excitation/emission)] or LP (r = -0.85, 235/285  nm)
      concentrations. Due to overlapping, the changes in emission could not be linked
      specifically to the recorded cross-links. However, the fluorescence signal
      enabled a nondestructive optical estimate of changes in the pentosidine and LP
      cross-linking of intact articular cartilage.

PMID- 22975680
TI  - On the noninvasive optical monitoring and differentiation of methemoglobinemia
      and sulfhemoglobinemia.
AB  - There are several pathologies whose study and diagnosis is impaired by a
      relatively small number of documented cases. A practical approach to overcome
      this obstacle and advance the research in this area consists in employing
      computer simulations to perform controlled in silico experiments. The results of
      these experiments, in turn, may be incorporated in the design of differential
      protocols for these pathologies. Accordingly, in this paper, we investigate the
      spectral responses of human skin affected by the presence of abnormal amounts of
      two dysfunctional hemoglobins, methemoglobin and sulfhemoglobin, which are
      associated with two life-threatening medical conditions, methemoglobinemia and
      sulfhemoglobinemia, respectively. We analyze the results of our in silico
      experiments and discuss their potential applications to the development of more
      effective noninvasive monitoring and differentiation procedures for these medical
      conditions.

PMID- 22975681
TI  - Isoform-specific roles of the GTPase activating protein Nadrin in cytoskeletal
      reorganization of platelets.
AB  - Cytoskeletal reorganization of activated platelets plays a crucial role in
      hemostasis and thrombosis and implies activation of Rho GTPases. Rho GTPases are
      important regulators of cytoskeletal dynamics and function as molecular switches
      that cycle between an inactive and an active state. They are regulated by GTPase
      activating proteins (GAPs) that stimulate GTP hydrolysis to terminate Rho
      signaling. The regulation of Rho GTPases in platelets is not explored. A detailed
      characterization of Rho regulation is necessary to understand activation and
      inactivation of Rho GTPases critical for platelet activation and aggregation.
      Nadrin is a RhoGAP regulating cytoplasmic protein explored in the central nervous
      system. Five Nadrin isoforms are known that share a unique GAP domain, a
      serine/threonine/proline-rich domain, a SH3-binding motif and an N-terminal BAR
      domain but differ in their C-terminus. Here we identified Nadrin in platelets
      where it co-localizes to actin-rich regions and Rho GTPases. Different Nadrin
      isoforms selectively regulate Rho GTPases (RhoA, Cdc42 and Rac1) and cytoskeletal
      reorganization suggesting that - beside the GAP domain - the C-terminus of Nadrin
      determines Rho specificity and influences cell physiology. Furthermore, Nadrin
      controls RhoA-mediated stress fibre and focal adhesion formation. Spreading
      experiments on fibrinogen revealed strongly reduced cell adhesion upon Nadrin
      overexpression. Unexpectedly, the Nadrin BAR domain controls Nadrin-GAP activity
      and acts as a guidance domain to direct this GAP to its substrate at the plasma
      membrane. Our results suggest a critical role for Nadrin in the regulation of
      RhoA, Cdc42 and Rac1 in platelets and thus for platelet adhesion and aggregation.

PMID- 22975682
TI  - Regulation of autophagosome formation by Rho kinase.
AB  - Macroautophagy, commonly referred to as autophagy, is a protein degradation
      pathway that functions at a constitutive level in cells, which may become further
      activated by stressors such as nutrient starvation or protein aggregation.
      Autophagy has multiple beneficial roles for maintaining normal cellular
      homeostasis and these roles are related to the implications of autophagy in
      disease mechanisms including neurodegeneration and cancer. We previously searched
      for novel autophagy regulators and identified Rho-kinase 1 (ROCK1) as a
      candidate. Here, we show that activated ROCK1 inhibits autophagy in human
      embryonic kidney 293 cells. Conversely, ROCK inhibitory compounds enhanced the
      autophagy response to amino acid starvation or rapamycin treatment. Inhibition of
      ROCK during the starvation period led to a more rapid response with the
      production of larger early autophagosomes that matured into enlarged late
      degradative autolysosomes. Despite the production of enlarged LC3-positive early
      autophagosomes, membrane precursors containing WD-repeat protein interacting with
      phosphoinositides 1 (WIPI1) and mammalian Atg9 were not affected by ROCK
      inhibition, suggesting that phagophore elongation had been unusually extended.
      However, the enlarged autophagosomes were enriched in ULK1 which was essential to
      allow progression of autophagy flux. Our results demonstrate a novel role for
      ROCK in the control of autophagosome size and degradative capacity.

PMID- 22975683
TI  - Syndecan 4 regulation of PDK1-dependent Akt activation.
AB  - The phosphatidylinositol 3 kinase (Pi3K)/Akt pathway is a major regulator of cell
      growth, proliferation, metabolism, survival, and angiogenesis. Despite extensive
      study, a thorough understanding of the modulation and regulation of this pathway
      has remained elusive. We have previously demonstrated that syndecan 4 (S4)
      regulates the intracellular localization of mTORC2, thus altering phosphorylation
      of Akt at serine473 (Ser473), one of two critical phosphorylation sites essential
      for the full activation of Akt [1]. Here we report that S4 also regulates the
      phosphorylation of Akt at threonine308 (Thr308), the second phosphorylation site
      required for the full Akt activation. A deletion of S4 resulted in lower levels
      of Thr308 phosphorylation both in vitro and in vivo. Furthermore, a deletion or
      knockdown of the S4 effector molecule PKCalpha led to a similar reduction in
      phosphorylation of Thr308 while overexpression of myristoylated PKCalpha rescued
      AktThr308 phosphorylation in endothelial cells lacking S4. Finally, PAK1/2 is
      also recruited to the rafts by the S4-PKCalpha complex and is required for AKT
      activation.

PMID- 22975684
TI  - The LMP2A protein of Epstein-Barr virus regulates phosphorylation of ITSN1 and
      Shb adaptors by tyrosine kinases.
AB  - Latent Membrane Protein 2A (LMP2A) is an Epstein-Barr virus-encoded protein that
      is important for the maintenance of latent infection. Its activity affects
      cellular differentiation, migration, proliferation and B cell survival. LMP2A
      resembles a constitutively activated B cell antigen receptor and exploits host
      kinases to activate a set of downstream signaling pathways. In the current study
      we demonstrate the interaction of LMP2A with intersectin 1 (ITSN1), a key
      endocytic adaptor protein. This interaction occurs via both the N- and C-tails of
      LMP2A and is mediated by the SH3 domains of ITSN1. Additionally, we identified
      the Shb adaptor and the Syk kinase as novel binding ligands of ITSN1. The Shb
      adaptor interacts simultaneously with the phosphorylated tyrosines of LMP2A and
      the SH3 domains of ITSN1 and mediates indirect interaction of ITSN1 to LMP2A. Syk
      kinase promotes phosphorylation of both ITSN1 and Shb adaptors in LMP2A
      expressing cells. In contrast to ITSN1, Shb phosphorylation depends additionally
      on Lyn kinase activity. Considering that Shb and ITSN1 are implicated in various
      receptor tyrosine kinase signaling, our results indicate that LMP2A can affect a
      number of signaling pathways by regulating the phosphorylation of the ITSN1 and
      Shb adaptors.

PMID- 22975685
TI  - PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA
      damage.
AB  - PHD finger protein 20 (PHF20) is a transcription factor, which was originally
      identified in glioma patients. PHF20 appears to be a novel antigen in glioma, and
      has also termed glioma-expressed antigen 2. PHF20 is thought to contribute to the
      development of cancers, including glioblastoma, lung cancer, colon cancer and
      ovarian cancer. However, little is known about the function of PHF20 in various
      cancers. Here we report that PHF20 contains two consensus sites for protein
      kinase B (PKB) phosphorylation (RxRxxS/T). PKB can directly phosphorylate PHF20
      on Ser291 in vitro and in vivo. It has been shown that PKB participates in the
      tumor suppressor p53 regulated gene expression program and has a direct effect on
      p21 regulation after DNA damage. UV-induced DNA damage results in accumulation of
      p53 and PKB activation. Interestingly, PKB-mediated PHF20 phosphorylation led to
      an inhibition of p53 induction following UV treatment, leading to the reduction
      of p21 transcriptional activity. Using anti PHF20 and anti pPKB (S473)
      antibodies, these events were mapped in various human cancer tissues. Taken
      together, these data suggest that PHF20 is a novel substrate for PKB and its
      phosphorylation by PKB plays an important role in tumorigenesis via regulating of
      p53 mediated signaling.

PMID- 22975686
TI  - BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib
      and lenalidomide activities through NF-kappaB.
AB  - Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical
      activity in chronic lymphocytic leukaemia (CLL) effecting cell death through
      inhibition of Bruton's tyrosine kinase (BTK). In this study we report for the
      first time that ibrutinib is cytotoxic to malignant plasma cells from patients
      with multiple myeloma (MM) and furthermore that treatment with ibrutinib
      significantly augments the cytotoxic activity of bortezomib and lenalidomide
      chemotherapies. We describe that the cytotoxicity of ibrutinib in MM is mediated
      via an inhibitory effect on the nuclear factor-kappaB (NF-kappaB) pathway.
      Specifically, ibrutinib blocks the phosphorylation of serine-536 of the p65
      subunit of NF-kappaB, preventing its nuclear translocation, resulting in down
      regulation of anti-apoptotic proteins Bcl-xL, FLIP(L) and survivin and
      culminating in caspase-mediated apoptosis within the malignant plasma cells.
      Taken together these data provide a platform for clinical trials of ibrutinib in
      myeloma and a rationale for its use in combination therapy, particularly with
      bortezomib.

PMID- 22975687
TI  - Structural diversity of the cAMP-dependent protein kinase regulatory subunit in
      Caenorhabditis elegans.
AB  - The cAMP-dependent protein kinase (protein kinase A, PK-A) plays a key role in
      the control of eukaryotic cellular activity. The enzymology of PK-A in the free
      living nematode, Caenorhabditis elegans is deceptively simple. Single genes
      encode the catalytic (C) subunit (kin-1), the regulatory (R) subunit (kin-2) and
      an A-kinase anchor protein (AKAP) (aka-1); nonetheless, PK-A is able to
      facilitate a comprehensive array of cAMP-mediated processes in this model
      multicellular organism. We have previously demonstrated that, in C. elegans, as
      many as 12 different isoforms of the C-subunit arise as a consequence of
      alternative splicing strategies. Here, we report the occurrence of transcripts
      encoding novel isoforms of the PK-A R-subunit in C. elegans. In place of exons 1
      and 2, these transcripts include coding sequences from novel B or Q exons
      directly linked to exon 3, thereby generating isoforms with novel N-termini. R
      subunits containing an exon B-encoded N-terminal polypeptide sequence were
      detected in extracts prepared from mixed populations of C. elegans. Of note is
      the observation that R-subunit isoforms containing exon B- or exon Q-encoded
      polypeptide sequences lack the dimerisation/docking domains conventionally seen
      in R-subunits. This means that they are unlikely to participate in the formation
      of tetrameric PK-A holoenzymes and, additionally, they are unlikely to interact
      with AKAP(s). It is therefore possible that, in C. elegans, in addition to
      tetrameric (R(2)C(2)) PK-A holoenzymes, there is also a sub-population of dimeric
      (RC) PK-A enzymes that are not tethered by AKAPs. Furthermore, inspection of the
      N-terminal sequence encoded by exon B suggests that this isoform is a likely
      target for N-myristoylation. Although unusual, a number of similarly N
      myristoylatable R-subunits, from a range of different species, are present in the
      databases, suggesting that this may be a more generally observed feature of R
      subunit structure. The occurrence of R-subunit isoforms, without
      dimerisation/docking domains (with or without N-myristoylatable N-termini) in
      other species would suggest that the control of PK-A activity may be more complex
      than hitherto thought.

PMID- 22975688
TI  - Evaluation of different contour feather types for biomonitoring lead exposure in
      Northern goshawk (Accipiter gentilis) and tawny owl (Strix aluco).
AB  - The concentration of Pb was determined in feathers (contour feathers: mantle,
      pectoral, ventral, and primary- and secondary-coverts) of two sedentary species
      of raptors in Galicia (NW Spain): the tawny owl (Strix aluco) and the Northern
      goshawk (Accipiter gentilis). A high degree of intraindividual variability was
      observed in all types of feathers, with coefficients of variation exceeding 100
      percent. The correlations between feather types were too low to enable use of a
      single type of body feather to predict the concentration of Pb in the other
      feathers. The number of body feathers required to differentiate individuals on
      the basis of the concentration of Pb was extremely high, in some cases higher
      than the number of the particular type of feather in the bird. All of this
      provides clear evidence that the contour and covert feathers of the raptor
      species considered cannot be used to biomonitor contamination by Pb, at least in
      this sample where the overall feather concentration were fairly uniform.

PMID- 22975689
TI  - Cd2+ toxicity as affected by bare TiO2 nanoparticles and their bulk counterpart.
AB  - Toxicity of engineered nanoparticles has received extensive attention in recent
      years. However, nanoparticles always co-exist with other pollutants in natural
      environment. Whether there are any interactions between these classical
      pollutants and nanoparticles; and how these interactions may influence the
      environmental behavior, effects and fate of each other remain largely unclear.
      For this purpose, effects of bare titanium dioxide engineered nanoparticles
      (TiO(2)-NP) and their bulk counterpart (TiO(2)-BC) on Cd(2+) bioavailability and
      toxicity to the green alga Chlamydomonas reinhardtii were examined in the present
      study. We first investigated the kinetics and equilibrium isotherm of Cd(2+)
      adsorption on both particles in the algal culture medium. Pseudo-first-order
      adsorption kinetics was observed with equilibrium rate constant ranging from 0.19
      to 0.33min(-1). Increase in Cd(2+) adsorption with its ambient concentration at
      equilibrium followed a single Langmuir isotherm for different concentrations of
      TiO(2). Furthermore, surface-area-based Cd(2+) adsorption by TiO(2)-BC was higher
      than that by TiO(2)-NP in most Cd(2+) concentration treatments suggesting that
      particle size was not the only cause for different adsorption. Both forms of
      TiO(2) could alleviate Cd(2+) inhibitive effects on C. reinhardtii. However,
      Cd(2+) toxicity and its bioaccumulation were comparable as long as its free ion
      concentration in ambient toxicity media was similar regardless the particle size
      and concentration of TiO(2). There was no TiO(2) inside the algal cells either.
      Therefore, it was Cd(2+) adsorption by TiO(2) which decreased its ambient free
      ion concentration and further its intracellular accumulation as well as toxicity.

PMID- 22975690
TI  - Comparison of primary oxidants for water-oxidation catalysis.
AB  - In this tutorial review, we compare chemical oxidants for driving water-oxidation
      catalysts, focusing on the advantages and disadvantages of each oxidant.

PMID- 22975691
TI  - Calorimetric determination of the absorbed dose to water for medium-energy x-rays
      with generating voltages from 70 to 280 kV.
AB  - For medium energy x-rays produced with tube voltages from 70 to 280 kV, the
      absorbed dose to water, D(w), has been determined by means of water calorimetry
      with relative standard uncertainties ranging from 0.45% to 0.98% at 280 and 70
      kV. The results were confirmed by Monte Carlo calculations, in which the ratios
      of D(w) at 5 cm depth in a reference water phantom to the air kerma free in air,
      K(a), at the same point in space were compared to the corresponding ratios
      determined experimentally. The general agreement between measurement and
      calculation was better than 1%. These results confirm earlier investigations in
      which the absorbed dose to graphite was determined by means of a graphite
      extrapolation chamber. For the Monte Carlo calculations, an attempt was made to
      present a complete uncertainty budget, taking into account type B contributions
      also.

PMID- 22975692
TI  - [Emerging trends and technologies in JSRT annual meetings].

PMID- 22975693
TI  - [Comparison of the probability of meeting up with premature contraction during
      scanning in 320-area detector computed tomography with that in 64-multidetector
      CT coronary angiography].
AB  - BACKGROUND: Because coronary computed tomography angiography (CCTA) by 320-area
      detector CT (320-ADCT) can be obtained in a short time, the probability of
      meeting up with premature contraction (PC) during scanning may be lower in 320
      ADCT compared to 64-MDCT. The purpose is to compare the probability of meeting up
      with PC, scanning time, and image quality in patients with PC between the 2
      groups (320-ADCT vs 64-MDCT). METHODS: We have never rejected any CCTA
      examination due to arrhythmias. The 320-ADCT was performed in 2424 consecutive
      patients to include 70 atrial fibrillations (Afibs) and 64-MDCT in 1905
      consecutive patients to include 51 Afibs. After exclusion of the patients with
      Afibs, we studied the probability of meeting up with PC during scanning and we
      compared the scanning time, image quality, and reconstruction phase for patients
      with PC between the 2 groups. RESULTS: The probability of meeting up with PC
      during scanning in 320-ADCT (2.0%) is significantly lower (P<0.0001) than 64-MDCT
      (5.6%). For patients with PC, scanning time in 320-ADCT (2.9+/-0.6 s) was
      significantly shorter (P<0.0001) than 64-MDCT (9.5+/-1.9 s) and image quality in
      320-ADCT (2.9+/-0.3 points) was significantly higher (P<0.0001) than 64-MDCT
      (2.2+/-0.8 points). CCTA was reconstructed in mid-diastolic phase in 93% of
      patients with PC using the 320-ADCT with arrhythmia rejection system. CONCLUSION:
      The scanning time of 320-ADCT was 1/3 in comparison with that of 64-MDCT, and the
      probability of meeting up with PC during scanning in 320-ADCT was 1/3 in
      comparison with that in 64-MDCT.

PMID- 22975694
TI  - [Physical image properties of digital radiography systems in low dose range].
AB  - We measured physical image properties of a flat panel detector (FPD) system and a
      computed radiography (CR) system, targeting to a low dose range (reference dose:
      2.58*10(-7) C/kg: to 1/20 dose). Input-output properties, pre-sampled modulation
      transfer functions (pre-sampled MTFs), and normalized noise power spectra for an
      FPD system equipped with a CsI scintillator (FPDcsi) and a CR system with an
      imaging plate coated with storage phosphor (CR) were measured at the low dose
      range for radiation quality of RQA3 (?50 skV) and RQA5 (?70 kV), and detective
      quantum efficiencies (DQEs) were calculated. In addition, in order to validate
      the DQE results, component fractions of Poisson and multiplicative and additive
      noise were analyzed using relative standard deviation analysis. The DQE values of
      FPDcsi were decreased with dose decrease, and contrarily to these, those of CR
      were increased. At the 1/10 and 1/20 doses for RQA3, the DQEs of FPDcsi and CR
      became almost the same. From the results of RSD analysis, it was proved that the
      main cause of DQE deterioration on FPDcsi are non-negligible additive
      (electronic) noise, and the DQE improvement on CR was caused by both of
      significant multiplicative (structure) noise and very low electronic noise. The
      DQE results were validated by comparing burger phantom images of each dose and
      radiation quality.

PMID- 22975695
TI  - [Reduction of radiation exposure and image quality using dose reduction tool on
      computed tomography fluoroscopy].
AB  - The purpose of our study was to measure the reduction rate of radiation dose and
      variability of image noise using the angular beam modulation (ABM) on computed
      tomography (CT) fluoroscopy. The Alderson-Rando phantom and the homemade phantom
      were used in our study. These phantoms were scanned at on-center and off-center
      positions at -12 cm along y-axis with and without ABM technique. Regarding the
      technique, the x-ray tube is turned off in a 100-degree angle sector at the
      center of 12 o'clock, 10 o'clock, and 2 o'clock positions during CT fluoroscopy.
      CT fluoroscopic images were obtained with tube voltages, 120 kV; tube current
      time product per reconstructed image, 30 mAs; rotation time, 0.5 s/rot; slice
      thickness, 4.8 mm; and reconstruction kernel B30s in each scanning. After CT
      scanning, radiation exposure and image noise were measured and the image
      artifacts were evaluated with and without the technique. The reduction rate for
      radiation exposure was 75-80% with and without the technique at on-center
      position regardless of each angle position. In the case of the off-center
      position at -12 cm, the reduction rate was 50% with and without the technique. In
      contrast, image noise remained constant with and without the technique. Visual
      inspection for image artifacts almost have the same scores with and without the
      technique and no statistical significance was found in both techniques (p>0.05).
      ABM is an appropriate tool for reducing radiation exposure and maintaining image
      noise and artifacts during CT fluoroscopy.

PMID- 22975696
TI  - [Different educational programs on medical ultrasound examination for
      radiological technologists and medical technologists].
AB  - Radiological technologists (RTs) and medical technologists (MTs) are legally
      allowed to work as sonographers performing medical ultrasound examination.
      Despite the total number, much fewer RTs work as sonographers than MTs. To
      explore the reason, we investigated educational programs, universities, and
      colleges for both specialties. First, we established five categories of
      sonographers' competency: 1) Anatomy for imaging diagnosis, 2) Diseases and
      diagnosis, 3) Imaging, 4) Structure and principle of the equipment, and 5)
      Evaluation of image quality, using competence reported by the International
      Society of Radiographers and Radiological Technologists (ISRRT) and diagnostic
      competency required of sonographers in Japan. Using these categories, we analyzed
      the content and total instruction time by lectures and seminars based on
      information written in the syllabi, and explored the differences in education
      related to sonographers' competency in both programs. "Anatomy for imaging
      diagnosis" was taught in 15 RT programs (93.8%), and 6 MT programs (31.6%).
      "Diseases and diagnosis" was taught in 13 RT programs (86.7%), and 8 MT programs
      (53.3%). "Imaging" was taught in 14 RT programs (100%), and 13 MT programs
      (76.5%). "Structure and principle of the equipment" was taught in 12 RT programs
      (85.7%), and 6 MT programs (31.6%). "Evaluation of image quality" was taught in
      11 RT programs (84.6%), and 3 MT programs (15.0%). The average instruction time
      for RT was longer than for MT programs in all categories. RTs are educated and
      have a foundation to be sonographers at graduation, and may have the possibility
      to expand their career in this field.

PMID- 22975697
TI  - [Influence on measurements of pre-irradiation due to differences in ionization
      chamber shape or frequency in use].
AB  - Ionization chamber measurements in radiation therapy should be repeatedly
      performed until a stable reading is obtained. Ionization chambers exhibit a
      response which depends on time elapsed since the previous irradiation. In this
      study, we investigated the response of a set of two Farmer-style, one Plane
      parallel, and seven small ionization chambers, which are exposed to 4, 6, 10, and
      14 MV. The results show that Farmer-style and Plane parallel ionization chambers
      settle quickly within 9-20 min. On the other hand, small ionization chambers
      exhibit settling times of 12-33 min for 6, 10, and 14 MV. It will take longer for
      a settling time of 4 MV. The settling time showed time dependent irradiation. The
      first reading was up to 0.76% lower in the Farmer-style and Plane parallel
      ionization chambers. The small ionization chambers had a 2.60% lower first
      reading and more gradual response in reaching a stable reading. In this study,
      individual ionization chambers can vary significantly in their settling behavior.
      Variation of the responses on ionization chambers were confirmed not only when
      radiation was not used for a week but also when it was halted for a month. Pre
      irradiation of small ionization chambers is clearly warranted for eliminating
      inadvertent error in the calibration of radiation beams.

PMID- 22975698
TI  - [The examination of attenuation correction using one computed tomography scan in
      myocardial perfusion stress-rest single photon emission computed tomography].
AB  - Attenuation correction (AC) of myocardial perfusion stress-rest single photon
      emission computed tomography (SPECT) with hybrid SPECT/computed tomography (CT)
      is effective. But because CT scan is done two times, the radiation exposure of
      patients increases. Therefore, we suggested a new method of AC that can correct
      attenuation of SPECT images acquired during a rest examination by using the CT
      scan during a stress examination. AC was done using one CT scan and we evaluated
      the clinical appropriateness of using this method. Matters of this study were (1)
      positional reproducibility of data analysis machine (Xeleris) (2) phantom study:
      accuracy of registration by manual and repetition reproducibility (3) clinical
      study using (99m)Tc-tetrofosmin. Comparison methods were analyzed by calculating
      the difference perfusion (Dp) with 17-segments model of American Heart
      Association and visual evaluation of three axis images in the myocardium. In the
      phantom study, because most of the score of 17-segments accord (Dp<=1), it was
      considered that the shift on SPECT/CT's bed was reproduced by the shift on
      Xeleris. And it is shown that AC with CT scan on deference point was accuracy. In
      the clinical study, there were a few differences in Dp (Dp<=4) and approximately
      equal evaluation on visual evaluation was provided, which compared with
      conventional methods. Because AC of myocardial perfusion stress-rest SPECT by one
      CT scan showed that it was approximately equal in evaluation compared with
      conventional methods, we expect to be able to use this method in clinical cases.

PMID- 22975700
TI  - [The protocol of dose reduction in liver perfusion computed tomography].
AB  - Cerebral perfusion computed tomography (CT) has been widespread, but abdominal
      perfusion CT has not been very popular because there has been a problem with
      regard to the limit of irradiation range and respiratory effects. Recently, it
      became easy to perform perfusion of abdominal organs because the use of multi
      detector row CT (MDCT) has been extensive. Along with it, the number of hospitals
      that perform liver perfusion CT has increased. However, patient dose of the liver
      perfusion CT is very high, making it very important to reduce patient dose. We
      created the virtual data that reduced the number of irradiation by partly
      reducing the data obtained on the liver perfusion CT. We compared the analysis
      results of all data with that of the partly reduced. It is possible to reduce the
      patient dose by reducing the number of irradiation because there was no
      significant difference in the analysis results.

PMID- 22975699
TI  - [Evaluation of low dose chest expiratory high resolution computed tomography for
      diagnosis of air trapping].
AB  - In our hospital, expiratory high resolution computed tomography (HRCT) is being
      performed in patients with chronic obstructive pulmonary disease (COPD). Because
      expiratory HRCT is used in combination with inspiratory HRCT, it can provide less
      exposure according to diagnostic purposes. In the present study, we tried low
      dose expiratory HRCT in terms of visual assessment and analysis software of
      phantom experiments. As a result, visual assessment in the dose reduction rate
      was about 50% to 75% against conventional exposure doses. Thoracic examinations
      are common in organs with high tissue weighting factors, and the present study
      shows a very effective means for medical exposure reduction.

PMID- 22975701
TI  - [Symposium 3: Basic technology to support the development of magnetic resonance
      imaging "creating new technologies based on study of the past"].

PMID- 22975702
TI  - [Introduction to statistical methods for radiologic technology].

PMID- 22975703
TI  - [Radiotherapy technology--basic strategy. Summary].

PMID- 22975704
TI  - [Breast examination (6)--ultrasonography].

PMID- 22975705
TI  - [Clinical application of perfusion MR imaging using arterial spin labeling].

PMID- 22975708
TI  - [Evaluation of the revision 2012 in the medical payment system, and introduction
      of the medical economic activities].

PMID- 22975709
TI  - Estradiol inhibits the activity of proton-coupled amino acid transporter PAT1
      expressed in Xenopus oocytes.
AB  - Estrogen has great potential as a therapeutic agent in focal ischemic brain
      injury. Amino acids as energy resources and neurotransmitters in the central
      nervous system are crucial for proper neuronal function and excitability. The
      proton-coupled amino acid transporter PAT1 has clear potential in drug
      absorption. In this paper, human brain PAT1 was cloned and expressed in Xenopus
      oocytes. The effects of estradiol on the activity of PAT1 were investigated.
      Glycine-induced membrane currents mediated by PAT1 were measured using the two
      electrode voltage clamp technique. The amplitude of the glycine-elicited current
      was decreased progressively with increasing concentrations of beta-estradiol. A
      concentration-dependent outwards current of PAT1 was also detected by the
      presence of beta-estradiol. We conclude that estrogen attenuates the activity of
      PAT1 by directly closing PAT1 channel. Our results may provide an additional
      mechanism for estrogen on neurotransmission and neuronal metabolism during
      ischemic injury.

PMID- 22975710
TI  - Clopidogrel delays gastric ulcer healing in rats.
AB  - Clopidogrel is not safe enough for the gastric mucosa in patients with high risk
      of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer
      healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats
      and the ulcer size, mucosal epithelial cell proliferation of the ulcer margin,
      expression of growth factors [epidermal growth factor (EGF), basic fibroblast
      growth factor] and their receptors, and signal transduction pathways for cell
      proliferation were measured and compared between the clopidogrel-treated group
      and untreated controls. For the in vitro part, rat gastric mucosal epithelial
      cell line (RGM-1 cells) was used to establish EGF receptor over-expressed cells.
      Cell proliferation and molecular change under EGF treatment (10ng/ml) with and
      without clopidogrel (10(-6)M) were demonstrated. Ulcer size was significantly
      larger in the clopidogrel-treated group compared to the control and mucosal
      epithelial cell proliferation of the ulcer margin was significantly decreased in
      the clopidogrel-treated group (P<0.05). Clopidogrel (2mg and 10mg/kg/day)
      significantly decreased ulcer-induced gastric epithelial cell proliferation and
      ulcer-stimulated expressions of EGF receptor and phosphorylated extracellular
      signal-regulated kinase (PERK) at the ulcer margin (P<0.05). Clopidogrel (10(
      6)M) also inhibited EGF-stimulated EGF receptor, PERK expression, and cell
      proliferation in RGM-1 cells (P<0.05), and caused much less inhibition of EGF
      stimulated cell proliferation in EGF receptor over-expressed RGM-1 cells than in
      RGM-1 cells (22% vs. 32% reduction). In conclusion, clopidogrel delays gastric
      ulcer healing in rats via inhibiting gastric epithelial cell proliferation, at
      least by inhibition of the EGF receptor-ERK signal transduction pathway.

PMID- 22975711
TI  - Atrial natriuretic peptide prevents the mitochondrial permeability transition
      pore opening by inactivating glycogen synthase kinase 3beta via PKG and PI3K in
      cardiac H9c2 cells.
AB  - The purpose of this study was to test if atrial natriuretic peptide (ANP) can
      prevent the mitochondrial permeability transition pore (mPTP) opening by
      inactivating glycogen synthase kinase 3beta (GSK-3beta). ANP prevented loss of
      mitochondrial membrane potential (DeltaPsi(m)) caused by H(2)O(2) in a dose
      dependent manner. Similarly, cyclosporin A, an inhibitor of the mPTP opening,
      could also preserve DeltaPsi(m). ANP increased GSK-3beta phosphorylation at
      Ser(9), pointing to that ANP inactivates GSK-3beta. ANP could not prevent the
      loss of DeltaPsi(m) in cells transfected with the constitutively active GSK-3beta
      (GSK-3beta-S9A) mutant. The effects of ANP on GSK-3beta phosphorylation and
      DeltaPsi(m) were reversed by the selective PKG inhibitor KT5823 [2,3,9,10,11,12
      hexahydro-10R-methoxy-2,9-dimethyl-1-oxo-9S,12R-epoxy-1H-diindolo[1,2,3
      fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid, methyl
      ester]. In support, PKG markedly enhanced GSK-3beta phosphorylation. ANP-induced
      GSK-3beta phosphorylation was also abolished by the PI3K inhibitor LY294002 [2-(4
      morpholinyl-4H-1-benzopyran-4-one hydrochloride)] and ANP could not prevent
      H(2)O(2)-induced loss of DeltaPsi(m) in the presence of LY294002. These data
      suggest that ANP modulates the mPTP opening by inactivating GSK-3beta through PKG
      and PI3K. GSK-3beta is a common downstream target of PKG and PI3K. Prevention of
      the mPTP opening may underlie the mechanism for ANP's protection against
      reperfusion injury.

PMID- 22975712
TI  - Dual action molecules: bioassays of combined novel antioxidants and angiotensin
      II receptor antagonists.
AB  - In this study we have investigated the in vitro angiotensin II receptor
      antagonist and antioxidant activity of a series of compounds in which the
      antioxidant pharmacophores (selenium, phenol, benzothiophene, ebselen or
      nitroxide) have been incorporated into the AT(1) receptor antagonist (sartan)
      milfasartan. Activity of these compounds was assessed in tissue-based assays. The
      novel molecules (30nM), nitrasartan or phenol-milfasartan, retained AT(1)
      receptor antagonist potency in rat isolated right atria. Antioxidant capacity of
      the substituted sartans was examined in an AAPH (2,2'-azobis (2-amidinopropane)
      hydrochloride)-induced haemolysis assay (mouse C57/BL6 isolated erythrocytes).
      Each of the antioxidant pharmacophores (10MUM), except benzothiophene, protected
      against radical-mediated lysis. Of the novel sartans, only analogues
      incorporating selenium, phenol or nitroxide (nitrasartan) protected against
      radical-induced haemolysis. In the tissue-based assay using mouse isolated paced
      left atria, the free radical generator doxorubicin (30MUM) resulted in a decrease
      in left atrial force over 90min. In this assay the phenol, nitroxide or ebselen
      antioxidant pharmacophores protected against doxorubicin-induced negative
      inotropy but selenocystine and benzothiophene did not. Nitrasartan (10MUM) was
      the only novel analogue to protect against radical-induced negative inotropy.
      Nitrasartan also antagonised angiotensin II responses and decreased superoxide
      production in a concentration-dependent manner in rat isolated carotid arteries
      and aortae, respectively. In conclusion, nitrasartan is a dual action molecule
      demonstrating both AT(1) receptor antagonist potency and antioxidant properties
      in vitro.

PMID- 22975713
TI  - Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated
      with primary percutaneous coronary intervention for ST-segment elevation
      myocardial infarction: a substudy of the RISK-PCI trial.
AB  - Stent thrombosis (ST) is an important cause of death after primary percutaneous
      coronary intervention (pPCI). This substudy aimed at evaluating the usefulness of
      the RISK-PCI score, originally developed for the prediction of 30-day major
      adverse cardiovascular events, to predict the occurrence of ST after pPCI. We
      analyzed 1972 consecutive patients who underwent pPCI with stent implantation
      between February 2007 and December 2009. Early ST (EST), late ST (LST), and
      cumulative 1-year ST (CST) were the predefined end points. Definite, probable,
      and possible ST were included. Models discrimination and calibration to predict
      ST was tested using receiver-operating characteristics curves and the goodness-of
      fit (GoF) test. Sensitivity analyses and 1000-resample bootstrapping were used to
      evaluate the model's performance. The rates of EST, LST, and CST were 4.6, 1.4,
      and 6.0 %, respectively. Compared with controls, the cumulative ST group was
      associated with much higher rates of adverse clinical outcomes at 30-day follow
      up (adjusted odds ratio (OR) for death 6.45, adjusted OR for major bleeding 4.41)
      and at 12-month follow-up (adjusted OR for death 7.35, adjusted OR for major
      bleeding 4.56). Internal validation confirmed a reasonably good discrimination
      and calibration of the RISK-PCI score for the prediction of EST (area under the
      curve (AUC) 0.71, GoF 0.42), LST (AUC 0.69, GoF 0.36), and CST (AUC 0.70, GoF
      0.22) after pPCI. ST after pPCI is associated with adverse 30-day and 1-year
      clinical outcomes. We conclude that the risk of ST could be accurately assessed
      using the RISK-PCI score, which might help in deciding upon measures aimed at
      preventing adverse prognosis. 

PMID- 22975714
TI  - The association between obesity and acute myocardial infarction is age- and
      gender-dependent in a Japanese population.
AB  - Controversies concerning the association between obesity and acute myocardial
      infarction (AMI) are still ongoing in Japan. We investigated the association
      between obesity defined by body mass index of 25 kg/m(2) or higher and AMI by a
      case-control study using data from 1199 AMI cases and 4056 apparently healthy
      controls. The analysis was performed in age- and sex-matched samples of 621 case
      control pairs younger than 80 years and in crude samples aged 40-79 years divided
      into 10-year age groups. Prevalence of obesity, diabetes, current smoking,
      hypertension, and hypercholesterolemia were compared between cases and controls,
      and a multivariable odds ratio (OR) of AMI was calculated for each risk factor in
      various age groups. The OR (95 % confidence interval (CI)) of AMI for obesity was
      1.63 (1.23-2.17), P = 0.0008 in men younger than 80 years; 2.65 (1.41-5.00), P =
      0.0025 in women younger than 80 years; 2.23 (1.46-3.41), P = 0.0002 in men aged
      59 years or younger; 1.34 (0.90-2.01), P = 0.1510 in men aged 60-79 years; and
      2.98 (1.56-5.71), P = 0.0010 in women aged 60-79 years using paired samples. The
      OR (95 % CI) of AMI for obesity was 4.92 (2.53-9.58), P < 0.0001 in men aged 40
      49 years; 1.54 (1.07-2.21), P = 0.0197 in men aged 50-59 years; 1.07 (0.69-1.66),
      P = 0.7717 in men aged 60-69 years; 2.24 (1.20-4.20), P = 0.0118 in men aged 70
      79 years; 2.48 (1.12-5.48), P = 0.0245 in women aged 60-69 years; and 3.05 (1.46
      6.37), P = 0.0029 in women aged 70-79 years using crude samples. The association
      between obesity and AMI was age- and gender-dependent in a Japanese population. 

PMID- 22975715
TI  - Relationship between atrial conduction delay and obstructive sleep apnea.
AB  - Prolonged P-wave duration, indicating atrial conduction delay, is a marker of
      left atrial abnormality and is reported as a potent precursor of atrial
      fibrillation (AF). Several studies have shown that obstructive sleep apnea (OSA)
      is associated with AF. We evaluated the relationship between OSA and prolonged P
      wave duration. Consecutive subjects who underwent overnight polysomnography and
      showed a normal sinus rhythm, had no history of AF or ischemic heart disease, and
      showed no evidence of heart failure were enrolled. Apnea-hypopnea index (AHI) is
      defined as the number of apnea and hypopnea events per hour of sleep. P-wave
      duration was determined on the basis of the mean duration of three consecutive
      beats in lead II from a digitally stored electrocardiogram. A total of 250
      subjects (middle-aged, predominantly male, mildly obese, with a mean P-wave
      duration of 106 ms) were enrolled. In addition to age, male gender, body mass
      index (BMI), hypertension, dyslipidemia, and uric acid and creatinine levels, AHI
      (r = 0.56; P < 0.001) had significant univariable relationship with P-wave
      duration. Multivariate regression analysis showed that age, BMI, male gender, and
      AHI (partial correlation coefficient, 0.47; P < 0.001) were significantly
      independently correlated to P-wave duration. Severity of OSA is significantly
      associated with delayed atrial conduction time. Obstructive sleep apnea may lead
      to progression of atrial remodeling as an AF substrate. 

PMID- 22975716
TI  - Optimal initial diagnostic strategies for the evaluation of stable angina
      patients: a multicenter, prospective study on myocardial perfusion imaging,
      computed tomographic angiography, and coronary angiography.
AB  - BACKGROUND: For stable patients suspected of having coronary artery disease
      (CAD), myocardial perfusion imaging (MPI) or computed tomographic angiography
      (CT) is used for initial evaluation, while coronary angiography (CAG) is used for
      confirming the diagnosis. The choice of the initial diagnostic test might
      influence the treatment strategy. METHODS AND RESULTS: Patients scheduled for
      MPI, CT, or CAG as the initial diagnostic test were enrolled. The primary and
      secondary end-points were a major adverse cardiac event (MACE) and
      revascularization, respectively. Of the 2,878 patients enrolled, 2,825 underwent
      initial diagnostic tests, and 2,780 were followed up for 1.42+/-0.49 years. After
      adjustment for CAD severity, Cox proportional hazard regression analysis showed
      that the risk of MACE in the MPI and CT groups were similar and significantly
      less than that in the CAG group (hazard ratio, 0.82 vs. 2.19; 95% confidence
      interval [CI], 0.43-1.58 vs. 1.40-3.44). Furthermore, the rate of
      revascularization in the MPI group was less than that of the CT (odds ratio,
      1.62; 95% CI, 1.20-2.18) and CAG (odds ratio, 5.36; 95% CI, 4.07-7.05) groups.
      CONCLUSIONS: These data indicate that for stable patients with suspected CAD, the
      use of MPI or CT as the initial diagnostic test was associated with better
      prognosis than the use of CAG, and that initial evaluation with MPI was
      associated with a lower requirement of coronary intervention.

PMID- 22975717
TI  - Changes in cardiovagal baroreflex sensitivity are related to increased
      ventricular mass in patients with liver cirrhosis.
AB  - BACKGROUND: Morphological and functional cardiac modifications attributable to
      neurohumoral activation and hyperdynamic circulation have been found in patients
      with liver cirrhosis (LC). Cardiovagal baroreflex sensitivity (BRS) has been
      shown to inversely correlate with left ventricular (LV) morphology. It was
      hypothesized that, in patients with cirrhotic cardiomyopathy, reduced BRS is
      associated with myocardial remodeling and increased LV mass index (LVMI). METHODS
      AND RESULTS: Eighty-two LC patients scheduled to undergo liver transplantation
      were evaluated. Spectral analysis was done of beat-by-beat blood pressure and
      heart rate (HR) time series and BRS was derived from their cross-spectral gain.
      Echocardiography before liver transplantation was used to evaluate heart
      morphology and function. BRS was inversely correlated with LV wall thickness
      (P=0.038), end-diastolic interventricular septum thickness (P=0.048), LVMI
      (P=0.005) and HR (P<0.001). On multivariate stepwise linear analysis LVMI and HR
      were independently associated with BRS. On tertile analysis of LVMI, compared
      with the lowest tertile of LVMI (75+/-11 g/m(2)), the highest tertile (118+/-13
      g/m(2)) showed significantly impaired BRS (4.6+/-2.3 vs. 6.4+/-3.1 ms/mmHg,
      P=0.012). CONCLUSIONS: Reduced cardiovagal BRS is associated with increased LV
      mass in patients with LC, suggesting a relationship between cardiovagal BRS
      control of HR and cardiac end-organ damage in patients with cirrhotic
      cardiomyopathy.

PMID- 22975718
TI  - Little evidence for demasculinization of the Drosophila X chromosome among genes
      expressed in the male germline.
AB  - Male-biased genes-those expressed at higher levels in males than in females-are
      underrepresented on the X chromosome of Drosophila melanogaster. Several
      evolutionary models have been posited to explain this so-called demasculinization
      of the X. Here, we show that the apparent paucity of male-biased genes on the X
      chromosome is attributable to global X-autosome differences in expression in
      Drosophila testes, owing to a lack of sex chromosome dosage compensation in the
      male germline, but not to any difference in the density of testis-specific or
      testis-biased genes on the X chromosome. First, using genome-wide gene expression
      data from 20 tissues, we find no evidence that genes with testis-specific
      expression are underrepresented on the X chromosome. Second, using contrasts in
      gene expression profiles among pairs of tissues, we recover a statistical
      underrepresentation of testis-biased genes on the X but find that the pattern
      largely disappears once we account for the lack of dosage compensation in the
      Drosophila male germline. Third, we find that computationally "demasculinizing"
      the autosomes is not sufficient to produce an expression profile similar to that
      of the X chromosome in the testes. Our findings thus show that the lack of sex
      chromosome dosage compensation in Drosophila testes can explain the apparent
      signal of demasculinization on the X, whereas evolutionary demasculinization of
      the X cannot explain its overall reduced expression in the testes.

PMID- 22975719
TI  - Reconstructing the demographic history of the human lineage using whole-genome
      sequences from human and three great apes.
AB  - The demographic history of human would provide helpful information for
      identifying the evolutionary events that shaped the humanity but remains
      controversial even in the genomic era. To settle the controversies, we inferred
      the speciation times (T) and ancestral population sizes (N) in the lineage
      leading to human and great apes based on whole-genome alignment. A coalescence
      simulation determined the sizes of alignment blocks and intervals between them
      required to obtain recombination-free blocks with a high frequency. This
      simulation revealed that the size of the block strongly affects the parameter
      inference, indicating that recombination is an important factor for achieving
      optimum parameter inference. From the whole genome alignments (1.9 giga-bases) of
      human (H), chimpanzee (C), gorilla (G), and orangutan, 100-bp alignment blocks
      separated by >=5-kb intervals were sampled and subjected to estimate tau = MUT
      and theta = 4MUgN using the Markov chain Monte Carlo method, where MU is the
      mutation rate and g is the generation time. Although the estimated tau(HC)
      differed across chromosomes, tau(HC) and tau(HCG) were strongly correlated across
      chromosomes, indicating that variation in tau is subject to variation in MU,
      rather than T, and thus, all chromosomes share a single speciation time.
      Subsequently, we estimated Ts of the human lineage from chimpanzee, gorilla, and
      orangutan to be 6.0-7.6, 7.6-9.7, and 15-19 Ma, respectively, assuming variable
      MU across lineages and chromosomes. These speciation times were consistent with
      the fossil records. We conclude that the speciation times in our recombination
      free analysis would be conclusive and the speciation between human and chimpanzee
      was a single event.

PMID- 22975720
TI  - The mitochondrial genome of Paraminabea aldersladei (Cnidaria: Anthozoa:
      Octocorallia) supports intramolecular recombination as the primary mechanism of
      gene rearrangement in octocoral mitochondrial genomes.
AB  - Sequencing of the complete mitochondrial genome of the soft coral Paraminabea
      aldersladei (Alcyoniidae) revealed a unique gene order, the fifth mt gene
      arrangement now known within the cnidarian subclass Octocorallia. At 19,886 bp,
      the mt genome of P. aldersladei is the second largest known for octocorals; its
      gene content and nucleotide composition are, however, identical to most other
      octocorals, and the additional length is due to the presence of two large,
      noncoding intergenic regions. Relative to the presumed ancestral octocoral gene
      order, in P. aldersladei a block of three protein-coding genes (nad6-nad3-nad4l)
      has been translocated and inverted. Mapping the distribution of mt gene
      arrangements onto a taxonomically comprehensive phylogeny of Octocorallia
      suggests that all of the known octocoral gene orders have evolved by successive
      inversions of one or more evolutionarily conserved blocks of protein-coding
      genes. This mode of genome evolution is unique among Metazoa, and contrasts
      strongly with that observed in Hexacorallia, in which extreme gene shuffling has
      occurred among taxonomic orders. Two of the four conserved gene blocks found in
      Octocorallia are, however, also conserved in the linear mt genomes of Medusozoa
      and in one group of Demospongiae. We speculate that the rate and mechanism of
      gene rearrangement in octocorals may be influenced by the presence in their mt
      genomes of mtMutS, a putatively active DNA mismatch repair protein that may also
      play a role in mediating intramolecular recombination.

PMID- 22975722
TI  - Redox-active ligands in catalysis.
AB  - Odd-electron, redox-active ligands are discussed in the context of catalysis. We
      focus on ligand-based, non-singlet state intermediates and their participation in
      catalytic processes and related stoichiometric transformations.

PMID- 22975721
TI  - Transcriptomic identification of iron-regulated and iron-independent gene copies
      within the heavily duplicated Trichomonas vaginalis genome.
AB  - Gene duplication is an important evolutionary mechanism and no eukaryote has more
      duplicated gene families than the parasitic protist Trichomonas vaginalis. Iron
      is an essential nutrient for Trichomonas and plays a pivotal role in the
      establishment of infection, proliferation, and virulence. To gain insight into
      the role of iron in T. vaginalis gene expression and genome evolution, we
      screened iron-regulated genes using an oligonucleotide microarray for T.
      vaginalis and by comparative EST (expressed sequence tag) sequencing of cDNA
      libraries derived from trichomonads cultivated under iron-rich (+Fe) and iron
      restricted (-Fe) conditions. Among 19,000 ESTs from both libraries, we identified
      336 iron-regulated genes, of which 165 were upregulated under +Fe conditions and
      171 under -Fe conditions. The microarray analysis revealed that 195 of 4,950
      unique genes were differentially expressed. Of these, 117 genes were upregulated
      under +Fe conditions and 78 were upregulated under -Fe conditions. The results of
      both methods were congruent concerning the regulatory trends and the
      representation of gene categories. Under +Fe conditions, the expression of
      proteins involved in carbohydrate metabolism, particularly in the energy
      metabolism of hydrogenosomes, and in methionine catabolism was increased. The
      iron-sulfur cluster assembly machinery and certain cysteine proteases are of
      particular importance among the proteins upregulated under -Fe conditions. A
      unique feature of the T. vaginalis genome is the retention during evolution of
      multiple paralogous copies for a majority of all genes. Although the origins and
      reasons for this gene expansion remain unclear, the retention of multiple gene
      copies could provide an opportunity to evolve differential expression during
      growth in variable environmental conditions. For genes whose expression was
      affected by iron, we found that iron influenced the expression of only some of
      the paralogous copies, whereas the expression of the other paralogs was iron
      independent. This finding indicates a very stringent regulation of the
      differentially expressed paralogous genes in response to changes in the
      availability of exogenous nutrients and provides insight into the evolutionary
      rationale underlying massive paralog retention in the Trichomonas genome.

PMID- 22975723
TI  - Robotic-assisted pedicle screw placement: lessons learned from the first 102
      patients.
AB  - INTRODUCTION: Surgeons' interest in image and/or robotic guidance for spinal
      implant placement is increasing. This technology is continually improving and may
      be particularly useful in patients with challenging anatomy. Only through careful
      clinical evaluation can its successful applications, limitations, and areas for
      improvement be defined. This study evaluates the outcomes of robotic-assisted
      screw placement in a consecutive series of 102 patients. METHODS: Data were
      recorded from technical notes and operative records created immediately following
      each surgery case, in which the robotic system was used to guide pedicle screw
      placement. All cases were performed at the same hospital by a single surgeon. The
      majority of patients had spinal deformity and/or previous spine surgery. Each
      planned screw placement was classified as: (1) successful/accurately placed screw
      using robotic guidance; (2) screw malpositioned using robot; (3) use of robot
      aborted and screw placed manually; (4) planned screw not placed as screw deemed
      non essential for construct stability. Data from each case were reviewed by two
      independent researchers to indentify the diagnosis, number of attempted robotic
      guided screw placements and the outcome of the attempted placement as well as
      complications or reasons for non-placement. RESULTS: Robotic-guided screw
      placement was successfully used in 95 out of 102 patients. In those 95 patients,
      949 screws (87.5 % of 1,085 planned screws) were successfully implanted. Eleven
      screws (1.0 %) placed using the robotic system were misplaced (all presumably due
      to "skiving" of the drill bit or trocar off the side of the facet). Robotic
      guidance was aborted and 110 screws (10.1 %) were manually placed, generally due
      to poor registration and/or technical trajectory issues. Fifteen screws (1.4 %)
      were not placed after intraoperative determination that the screw was not
      essential for construct stability. The robot was not used as planned in seven
      patients, one due to severe deformity, one due to very high body mass index, one
      due to extremely poor bone quality, one due to registration difficulty caused by
      previously placed loosened hardware, one due to difficulty with platform mounting
      and two due to device technical issues. CONCLUSION: Of the 960 screws that were
      implanted using the robot, 949 (98.9 %) were successfully and accurately
      implanted and 11 (1.1 %) were malpositioned, despite the fact that the majority
      of patients had significant spinal deformities and/or previous spine surgeries.
      "Tool skiving" was thought to be the inciting issue with the misplaced screws.
      Intraoperative anteroposterior and oblique fluoroscopic imaging for registration
      is critical and was the limiting issue in four of the seven aborted cases.

PMID- 22975724
TI  - Synthesis, characterization and photocatalytic activity of magnetically separable
      hexagonal Ni/ZnO nanostructure.
AB  - The hexagonal zinc oxide coated nickel (Ni/ZnO) nanostructure photocatalyst has
      successfully been prepared by the reduction of nickel chloride hexahydrate using
      hydrazine hydrate through the solvothermal process at 140  degrees C followed by
      surface modification of the product by the reflux method at 110  degrees C for 1
      h. The X-ray diffraction (XRD) pattern showed that the 'as prepared' sample
      consists of face centered cubic Ni and hexagonal wurtzite ZnO without any traces
      of impurity. Field emission scanning electron microscopy (FESEM) and transmission
      electron microscopy (TEM) images confirmed the formation of nickel nanoparticles
      under solvothermal conditions. These nickel nanoparticles, when subjected to
      reflux, formed the hexagonal zinc oxide coated nickel nanostructure. Fourier
      transform infrared (FTIR) spectra, photoluminescence (PL) and Raman studies also
      confirmed the presence of zinc oxide in the hybrid nanostructure. The growth
      mechanism for the development of the hexagonal zinc oxide coated nickel (Ni/ZnO)
      nanostructure has also been proposed. The appearance of the hysteresis loop, in
      the as-prepared Ni/ZnO hybrid nanostructure, demonstrated its ferromagnetic
      character at room temperature. The hexagonal Ni/ZnO nanostructure also acts as an
      efficient photocatalyst in the degradation of methylene blue under ultraviolet
      light irradiation. It is observed that the catalytic efficiency of the hybrid
      nanocatalyst is better compared to pure zinc oxide. Most importantly, the Ni/ZnO
      catalyst could also be easily separated, simply by applying an external magnetic
      field, and reused.

PMID- 22975725
TI  - Molecular characterization of Cryptosporidium species at the wildlife/livestock
      interface of the Kruger National Park, South Africa.
AB  - Molecular characterization of Cryptosporidium spp. was done on isolates from
      African elephant (Loxodonta africana), African buffalo (Syncerus caffer), impala
      (Aepyceros melampus) and native domestic calves collected during May and June
      2008 at the wildlife/livestock interface of the Kruger National Park (KNP), South
      Africa. A polymerase chain reaction (PCR) restriction fragment length
      polymorphism (RFLP) analysis of the 18S rRNA gene was used in feces from 51
      calves (3-12 months of age), 71 buffalo, 71 impala and 72 elephant, and
      sequencing of the 18S rRNA gene was done on PCR-RFLP-positive wildlife samples.
      Cryptosporidium spp. were detected in 8% (4/51) of the calves and identified as
      C. andersoni (2/4) and C. bovis (2/4). Four of the 214 wildlife samples were
      positive for Cryptosporidium with a prevalence of 2.8% each in impala and
      buffalo. Cryptosporidium ubiquitum was detected in two impala and one buffalo,
      and C. bovis in one buffalo. A concurrent questionnaire conducted among 120
      farmers in the study area investigated contacts between wildlife species and
      livestock. Buffalo and impala had the highest probability of contact with cattle
      outside the KNP. Despite the fairly low prevalence found in wildlife and cattle,
      the circulation of zoonotic Cryptosporidium spp., such as C. ubiquitum, should be
      investigated further, particularly in areas of high HIV infection prevalence.
      Further studies should target younger animals in which the prevalence is likely
      to be higher.

PMID- 22975726
TI  - Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6
      mice.
AB  - RATIONALE: Women are more sensitive than men to psychostimulants and progress
      from initial use to drug addiction more quickly. The mouse has been an under
      utilized model to study sex differences in psychostimulant action. Mice could
      serve as an ideal genetically tractable model for mechanistic studies into sex
      and hormone effects on psychostimulant behavior. OBJECTIVES: The objective of
      this study was to characterize psychostimulant effects in male and female mice
      with a combination of automated data collection and behavioral observation.
      METHODS: Male and female C57BL/6 mice (Charles River) were given a single dose or
      sequential ascending binge doses of D-amphetamine (AMPH) or cocaine (COC).
      Behavior was assessed in open field chambers using both automated photobeam
      interruptions and behavioral observations. Brain psychostimulant concentrations
      were determined at the time of maximum behavioral stimulation. RESULTS:
      Psychostimulants induced behavioral activation in mice including both increased
      locomotion as detected with an automated system and a sequence of behaviors
      progressing from stereotyped sniffing at low doses to patterned locomotion and
      rearing at high doses. Females exhibited more patterned locomotion and a shift
      towards higher behavior scores after either psychostimulant despite having lower
      AMPH and equivalent COC brain levels as males. CONCLUSIONS: Female C57BL/6 mice
      exhibit enhanced psychostimulant-induced behavior compared to males, similar to
      reports in rats. The combination of automated behavioral measures and behavioral
      observation was essential for verifying the existence of these differences. These
      results indicate the importance of testing both sexes when characterizing
      genetically manipulated mice to control for potential sex-specific effects.

PMID- 22975727
TI  - The stereotypy-inducing effects of N-substituted benztropine analogs alone and in
      combination with cocaine do not account for their blockade of cocaine self
      administration.
AB  - RATIONALE: Previous studies have demonstrated that several N-substituted 4', 4"
      diF-benztropine (BZT) analogs with high dopamine transporter affinity selectively
      decreased cocaine self-administration without affecting food-maintained behavior
      in rats. OBJECTIVES: The present study examined if the decreases in cocaine self
      administration are due to competition from excess behavioral activity
      (hyperlocomotion or stereotypy) induced by the BZT analogs alone or in
      combination with cocaine. RESULTS: Pretreatments with the typical dopamine uptake
      inhibitor methylphenidate [1.0, 3.2, and 10 mg/kg, intraperitoneally (i.p.)] dose
      dependently shifted the cocaine self-administration dose-effect curve (0, 0.032,
      0.1, 0.32, and 1.0 mg/kg/injection) leftward. The shift in the dose-effect curve
      was obtained at doses of methylphenidate that, when administered alone, also
      decreased food-maintained behavior and increased locomotor activity and
      stereotypy. In contrast, the N-substituted BZT analogs, JHW 007 (1.0, 3.2, and 10
      mg/kg, i.p.), AHN 1-055 (10 mg/kg), and, AHN 2-005 (10 mg/kg), as previously
      reported, decreased the maximum for the cocaine self-administration dose-effect
      curve, and did so at doses that were virtually without effects on food-maintained
      behavior. Further, the BZT analogs alone had minimal effects on locomotor
      activity and stereotypies and did not appreciably change the effects of cocaine
      on these measures when administered in combination with cocaine. CONCLUSIONS: The
      present results suggest that the decrease in cocaine self-administration produced
      by the N-substituted BZT analogs is due to an antagonism of the reinforcing
      effects of cocaine rather than due to interference from competing behavioral
      overstimulation, and further supports the development of N-substituted BZT
      analogs as medications to treat cocaine abuse.

PMID- 22975728
TI  - Cetuximab in combination with anti-human IgG antibodies efficiently down
      regulates the EGF receptor by macropinocytosis.
AB  - The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the
      epidermal growth factor receptor (EGFR). In addition, it is known that incubation
      with C225 induces endocytosis of the EGFR. This endocytosis has previously been
      shown to be increased when C225 is combined with an additional monoclonal anti
      EGFR antibody. However, the effects of antibody combinations on EGFR activation,
      endocytosis, trafficking and degradation have been unclear. By binding a
      secondary antibody to the C225-EGFR complex, we here demonstrate that a
      combination of antibodies can efficiently internalize and degrade the EGFR.
      Although the combination of antibodies activated the EGFR kinase and induced
      ubiquitination of the EGFR, the kinase activity was not required for
      internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the
      antibody combination efficiently degraded the EGFR without initiating downstream
      proliferative signaling. The antibody-induced internalization of EGFR was found
      not to depend on clathrin and/or dynamin, but depended on actin polymerization,
      suggesting induction of macropinocytosis. Macropinocytosis may cause
      internalization of large membrane areas, and this could explain the highly
      efficient internalization of the EGFR induced by combination of antibodies.

PMID- 22975729
TI  - Branched F-actin as a negative regulator of cilia formation.
AB  - Cilia dysfunction leads to developmental defects and also a spectrum of human
      diseases termed ciliopathies. The actin cytoskeleton is a highly dynamic network
      and involved in many important biological processes, such as cell migration and
      membrane trafficking. Recently, actin dynamics has been shown to play a critical
      role in ciliogenesis. This review summarizes these results and provides insight
      into possible mechanisms.

PMID- 22975730
TI  - S632A3, a new glutarimide antibiotic, suppresses lipopolysaccharide-induced pro
      inflammatory responses via inhibiting the activation of glycogen synthase kinase
      3beta.
AB  - Inflammatory mediators including inducible nitric oxide (iNOS), cyclooxygenase-2
      (COX-2), tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6)
      contribute to the course of a variety of inflammatory diseases. S632A3 is a new
      member of the glutarimide antibiotics isolated from a cultured broth of
      Streptomyces hygroscopicus S632 with a potent NF-kappaB inhibitory activity. In
      the present study, we investigated the anti-inflammatory effects and the
      underlying molecular mechanism of S632A3 on lipopolysaccharide (LPS)-stimulated
      RAW264.7 macrophages. S632A3 concentration-dependently inhibited LPS-induced NO
      and prostaglandin E(2) (PGE(2)) production through the suppression of iNOS and
      COX-2 at gene transcription levels. In addition, S632A3 suppressed NF-kappaB
      dependent inflammatory responses by inhibiting the activation of glycogen
      synthase kinase 3beta (GSK-3beta), while the activation of IkappaB kinase (IKK)
      complex was unaffected. S632A3 suppressed NF-kappaB activity by differentially
      affecting the CREB (cAMP response element-binding protein) and NF-kappaB p65
      interacting with the coactivator CBP (CREB binding protein). S632A3 also
      inhibited GSK-3beta-elicited iNOS and COX-2 expression. Moreover, S632A3 was
      shown to inhibit the activation of ASK1 (Apoptosis-signal regulating kinase 1)
      and p38 mitogen-activated protein kinase, therefore attenuated the LPS-induced NF
      kappaB activity in macrophages. Furthermore, S632A3 significantly reduced the pro
      inflammatory cytokines TNF-alpha and IL-6 production while increased the anti
      inflammatory cytokine IL-10 production in LPS-stimulated RAW264.7 cells. Our
      study thus provides a molecular mechanism by which S632A3 inhibited LPS-induced
      pro-inflammatory response in macrophages through interfering with the activation
      of GSK-3beta and ASK1-p38 signaling.

PMID- 22975731
TI  - Change in health-related quality of life amongst participants in a 4-month
      pedometer-based workplace health program.
AB  - BACKGROUND: Regular physical activity (PA) is associated with a reduced risk for
      chronic health conditions and improved health-related quality of life (HRQoL).
      Efforts to increase PA have included workplace health promotion. Currently,
      little is known about the effect of these programs on overall HRQoL. AIM: To
      evaluate whether participation in a pedometer-based PA program in the workplace
      was associated with changes in HRQoL. METHODS: 487 voluntary employees enrolled
      in a health program completed the SF-12 Health Survey at baseline and 4 months.
      Change in Physical and Mental component summary scores (PCS; MCS) was assessed
      with multivariable regression analysis, adjusting for covariates. RESULTS:
      Participation in the program was associated with an increase of 1.5 MCS units
      (95% CI: 0.76, -2.09). Greater improvements in MCS were observed in those
      reporting an increased level of PA during the program [1.9 (CI: 0.78, 2.92)
      versus 0.9 (CI: -0.12, 2.03)] and a lower baseline MCS score [6.3 (CI: 4.80,
      7.62) versus -1.5 (CI: -2.21, -0.80)]. No change in PCS was observed.
      CONCLUSIONS: Participation in this workplace PA program was associated with
      improvements in the mental component of HRQoL. We recommend the use of a broad
      perspective of health be used in both the implementation and evaluation of
      workplace PA programs.

PMID- 22975732
TI  - Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis
      with inadequate responses to methotrexate.
AB  - OBJECTIVES: We aimed to assess the efficacy of tacrolimus (TAC) as an add-on
      therapy in patients with rheumatoid arthritis (RA) who were previously treated
      with methotrexate (MTX) but not with biologics. METHODS: The study group (MTX +
      TAC group) consisted of 157 patients (selected from among the patients in the
      Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005
      to October 2009) who received add-on therapy with TAC in addition to MTX, but
      without biologics. A propensity score (PS) for the use of TAC was derived, and
      471 PS-matched patients who received MTX alone or MTX with other non-biologic
      disease-modifying antirheumatic drugs (except for TAC), but not with biologics,
      were selected and served as the control group. Changes in disease activity in the
      two groups during three consecutive IORRA phases were analyzed by adjusting for
      confounding factors. RESULTS: The median 28-joint disease activity score (DAS28)
      decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the
      control group. After adjusting for confounding factors, the decrease in the DAS28
      score in the MTX + TAC group was significantly larger (by 0.273 points) than that
      in the control group (P < 0.05). CONCLUSION: This study demonstrated the efficacy
      of add-on therapy with TAC to MTX in patients with RA in daily practice.

PMID- 22975733
TI  - Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis
      refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low
      field extremity MRI.
AB  - OBJECTIVE: Tocilizumab (TCZ) is effective in patients with rheumatoid arthritis
      (RA) who are refractory to anti-tumor-necrosis-factor (anti-TNF) biologics. The
      Rheumatoid Arthritis Society Disease Activity Score in 28 Joints (DAS28) is used
      to evaluate the response to TCZ. However, DAS28 is inappropriate marker because
      TCZ normalizes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
      in the early stage of treatment. The aim of our study was to test the usefulness
      of magnetic resonance imaging (MRI)-based markers of response to TCZ treatment.
      METHODS: Nine patients with RA who were refractory to anti-TNF inhibitors (six to
      infliximab, one to etanercept, one to adalimumab, and one to both) were assessed.
      MRI images of both hands were obtained by low-field extremity MRI at baseline,
      20, and 44 weeks of treatment, in addition to assessment with DAS28-ESR. The
      effect of TCZ on RA was examined by compact MRI score (cMRIS). RESULTS: All
      patients showed good or moderate response to TCZ treatment, as evaluated by
      significant reduction in DAS28-ESR at both 20 and 44 weeks (p < 0.001, each,
      relative to baseline). In contrast, MRI-based indexes (e.g., cMRIS, synovitis,
      edema, erosion scores) improved significantly at 44 weeks but not at 20 weeks.
      CONCLUSION: Differences in response to TCZ therapy were determined based on the
      method of evaluation, suggesting that MRI-based markers are potentially useful
      for evaluating RA response to TCZ therapy.

PMID- 22975734
TI  - Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients.
AB  - OBJECTIVES: The purpose of this study was to examine the treatment retention and
      efficacy of abatacept, the first member of a new class of biologic agents, in
      Japanese rheumatoid arthritis (RA) patients during clinical practice. METHODS: A
      retrospective multicenter study was conducted with patients who underwent
      abatacept therapy for 24 weeks (n = 143). RESULTS: Patients at baseline had a
      mean age of 63.5 years, a mean disease duration of 11.3 years, and a mean disease
      activity score in 28 joints (DAS28) of 4.5. Overall retention of abatacept
      treatment was 83.2 % at 24 weeks, when 46.2 % of patients achieved DAS28-defined
      low disease activity (LDA; DAS28 <3.2) and 26.6 % achieved DAS28-defined
      remission (DAS28 <2.6). LDA was achieved in a significantly higher proportion of
      patients without prior biologics therapy compared to those with prior biologics
      (60.9 vs. 34.2 %, p = 0.001). There was no significant difference between
      patients with or without concomitant methotrexate (MTX) therapy (45.2 vs. 47.5
      %). CONCLUSIONS: Abatacept therapy appears to be highly effective and well
      tolerated during clinical treatment of RA. Abatacept was particularly effective
      in patients with no history of biologics use, and did not appear to be dependent
      on concomitant MTX therapy.

PMID- 22975736
TI  - Probing the stoichiometry of the nitrification process using the respirometric
      approach.
AB  - Quantifying oxygen demand and nitrifier yield are important in the design and
      operation of advanced wastewater treatment systems. However, the accurate
      stoichiometry of the autotrophic nitrification process has not been fully
      developed. In this research, stoichiometric links between nitrifier yield,
      ammonia and nitrite oxidization, ammonia assimilation, and oxygen uptake for each
      step of the nitrification process were determined. A pulse-flow respirometer was
      used to measure the oxygen uptake for complete nitrification and nitrite
      oxidation reactions. Results indicated that the specific oxygen uptake was 4.23
      mg-O(2)/mg-N oxidized for complete nitrification, with 3.17 mg-O(2)/mg-N oxidized
      for ammonia oxidation (first step nitrification) and 1.06 mg-O(2)/mg-N oxidized
      for nitrite oxidation (second step nitrification). For the complete
      nitrification, fractions of ammonia used for electron donation, synthesis of
      ammonia oxidizers, and synthesis of nitrite oxidizers were 97.1%, 2.2%, and 0.7%,
      respectively. The fractions of electrons transferred into cell synthesis were
      approximately 7.5% for ammonia oxidation and 7.3% for nitrite oxidation. Biomass
      yield coefficients for ammonia oxidizers and nitrite oxidizers were 0.18 and 0.06
      g-VSS/g-N oxidized, respectively. These parameters are critical when calculating
      oxygen needs and nitrifier biomass concentrations during the design of advanced
      wastewater treatment processes.

PMID- 22975737
TI  - Determination of struvite crystallization mechanisms in urine using turbidity
      measurement.
AB  - Sanitation improvement in developing countries could be achieved through
      wastewater treatment processes. Nowadays alternative concepts such as urine
      separate collection are being developed. These processes would be an efficient
      way to reduce pollution of wastewater while recovering nutrients, especially
      phosphorus, which are lost in current wastewater treatment methods. The
      precipitation of struvite (MgNH(4)PO(4)?6H(2)O) from urine is an efficient
      process yielding more than 98% phosphorus recovery with very high reaction rates.
      The work presented here aims to determine the kinetics and mechanisms of struvite
      precipitation in order to supply data for the design of efficient urine treatment
      processes. A methodology coupling the resolution of the population balance
      equation to turbidity measurement was developed, and batch experiments with
      synthetic and real urine were performed. The main mechanisms of struvite
      crystallization were identified as crystal growth and nucleation. A satisfactory
      approximation of the volumetric crystal size distribution was obtained. The study
      has shown the low influence on the crystallization process of natural organic
      matter contained in real urine. It has also highlighted the impact of operational
      parameters. Mixing conditions can create segregation and attrition which
      influence the nucleation rate, resulting in a change in crystals number, size,
      and thus final crystal size distribution (CSD). Moreover urine storage conditions
      can impact urea hydrolysis and lead to spontaneous struvite precipitation in the
      stock solution also influencing the final CSD. A few limits of the applied
      methodology and of the proposed modelling, due to these phenomena and to the
      turbidity measurement, are also discussed.

PMID- 22975735
TI  - The control of elongation by the yeast Ccr4-not complex.
AB  - The Ccr4-Not complex is a highly conserved nine-subunit protein complex that has
      been implicated in virtually all aspects of gene control, including
      transcription, mRNA decay and quality control, RNA export, translational
      repression and protein ubiquitylation. Understanding its mechanisms of action has
      been difficult due to the size of the complex and the fact that it regulates
      mRNAs and proteins at many levels in both the cytoplasm and the nucleus.
      Recently, biochemical and genetic studies on the yeast Ccr4-Not complex have
      revealed insights into its role in promoting elongation by RNA polymerase II.
      This review will describe what is known about the Ccr4-Not complex in regulating
      transcription elongation and its possible collaboration with other factors
      traveling with RNAPII across genes. This article is part of a Special Issue
      entitled: RNA polymerase II Transcript Elongation.

PMID- 22975738
TI  - Effect of microbubble and its generation process on mixed liquor properties of
      activated sludge using Shirasu porous glass (SPG) membrane system.
AB  - Microbubble aeration is supposed to be able to provide potential advantage for
      aerobic biological wastewater treatment due to enhancement of oxygen mass
      transfer. On the other hand, microbubble and its generation methods might affect
      mixed liquor properties of activated sludge. Then SPG membrane microbubble
      generation system was used to investigate variation of mixed liquor properties of
      activated sludge in microbubble aeration. The results indicated that sludge
      floatation happened in microbubble aeration due to attachment of microbubbles to
      sludge flocs, resulting in a decrease in mixed liquor suspended solid (MLSS)
      concentration and poor sludge settleability. The strong shear stress caused by
      liquid circulation pump during microbubble generation led to sludge broken,
      resulting in decreased sludge floc size and sludge organics release, such as
      extracellular polymers (EPS). The organics release from broken sludge flocs was
      the main reason for increased both supernatant organic content (especially
      organic colloids) and consequent supernatant turbidity. The re-flocculation
      ability of broken sludge flocs also depended on sludge EPS release. In addition,
      the viscosity of mixed liquor increased along with sludge broken and increased
      supernatant organic content but the surface tension of mixed liquor remained
      constant. These results displayed the possible problems to apply microbubble
      aeration in aerobic wastewater treatment processes based on activated sludge.

PMID- 22975739
TI  - Reliability of infrared thermometric measurements of skin temperature in the
      hand.
AB  - STUDY DESIGN: Clinical measurement study. INTRODUCTION: Skin temperature
      asymmetries (STAs) are used in the diagnosis of complex regional pain syndrome
      (CRPS), but little evidence exists for reliability of the equipment and methods.
      PURPOSE: This study examined the reliability of an inexpensive infrared (IR)
      thermometer and measurement points in the hand for the study of STA. METHODS: ST
      was measured three times at five points on both hands with an IR thermometer by
      two raters in 20 volunteers (12 normals and 8 CRPS). RESULTS: ST measurement
      results using IR thermometers support inter-rater reliability: intraclass
      correlation coefficient (ICC) estimate for single measures 0.80; all ST
      measurement points were also highly reliable (ICC single measures, 0.83-0.91).
      CONCLUSIONS: The equipment demonstrated excellent reliability, with little
      difference in the reliability of the five measurement sites. These preliminary
      findings support their use in future CRPS research. LEVEL OF EVIDENCE: Not
      applicable.

PMID- 22975741
TI  - Rehabilitation protocol after suspension arthroplasty of thumb carpometacarpal
      joint osteoarthritis.
AB  - STUDY DESIGN: Retrospective case series. INTRODUCTION: When conservative
      modalities and therapies fail to control symptoms of thumb carpometacarpal (CMC)
      joint osteoarthritis, surgery may be indicated. PURPOSE OF THE STUDY: To present
      a rehabilitation protocol used in a series of patient cases after suspension
      arthroplasty and to evaluate outcomes. METHODS: Twenty-seven patients with CMC
      osteoarthritis were treated by the same arthroplasty technique and the same
      rehabilitation program. Patients were evaluated before and 12th week after
      surgery, and at the last follow-up using a visual analog scale; the Disability of
      the Arm, Shoulder, and Hand questionnaire; strength measurements; range of motion
      evaluations; and radiographic assessment. RESULTS: Average follow-up period was
      31.5 months. There was a decreasing trend in both subjective scores during follow
      ups (p=0.0001). Thirty-three percent and 30% improvements on radial and palmar
      abductions, respectively, and 29% improvement on pinch strengths were recorded at
      the final follow-up. Postoperative grip improvement was not preserved at the last
      follow-up. CONCLUSIONS: The results demonstrate a high degree of patient
      satisfaction suggesting the efficacy of this surgical technique and postoperative
      rehabilitation protocol. LEVEL OF EVIDENCE: Level 4.

PMID- 22975742
TI  - Histological differences of skin among three body regions in male and female
      Hokkaido sika deer (Cervus nippon yesoensis).
AB  - The Hokkaido sika deer (Cervus Nippon yesoensis), the largest and most abundant
      of the sika deer subspecies in Japan, has recently attracted new attention as a
      target for leather production, in addition to its meat value. To provide
      fundamental data for facilitating the effective use of skin for leather, the
      histological properties of skin at the shoulder, back and abdominal regions of
      male and female deer were compared. The results showed that the thickness of the
      outer skin layer was not significantly different across all regions irrespective
      of sex. Regarding collagen composition, we found that large-diameter collagen
      fibrils were heavily distributed in the shoulder of male deer, whereas small
      diameter collagen fibrils were largely confined to the abdomen of female deer. We
      hope this regional histological data will lead to more efficient processing of
      Hokkaido sika deer skin for leather production.

PMID- 22975743
TI  - Associations between kidney position and surplus renal arteries in horseshoe
      kidney: case report and analysis.
AB  - We report the anatomical findings of a case of horseshoe kidney, and analyze the
      associations between kidney position and surplus renal arteries in horseshoe
      kidneys found in Japanese autopsies in the past. The horseshoe kidney of our case
      fused at the lower poles of the original kidneys. Its right and left upper poles
      were at the middle region of the first and second lumbar vertebrae, respectively.
      The kidney was supplied by eight arteries. Our analysis of the correlation
      between the ascent of a horseshoe kidney and the number of surplus arteries found
      no significant association. However, there was a significant association between
      the region of the kidney where the surplus arteries entered and the location
      where they diverged from the aorta. Therefore, the ascent of a horseshoe kidney
      is not necessarily arrested because of the existence of many surplus arteries.
      After a horseshoe kidney partially ascends, the arteries which might become
      normal renal arteries are generated. In our case, we observed large splenomegaly,
      and noted that the left upper pole was the lowest compared with the horseshoe
      kidneys in the past autopsy reports. We suggest it is necessary to consider
      additional influences that determine the position of a horseshoe kidney.

PMID- 22975740
TI  - Assessment of upper extremity impairment, function, and activity after stroke:
      foundations for clinical decision making.
AB  - The purpose of this review is to provide a comprehensive approach for assessing
      the upper extremity (UE) after stroke. First, common UE impairments and how to
      assess them are briefly discussed. Although multiple UE impairments are typically
      present after stroke, the severity of one's impairment, paresis, is the primary
      determinant of UE functional loss. Second, UE function is operationally defined
      and a number of clinical measures are discussed. It is important to consider how
      impairment and loss of function affect UE activity outside of the clinical
      environment. Thus, this review also identifies accelerometry as an objective
      method for assessing UE activity in daily life. Finally, the role that each of
      these levels of assessment should play in clinical decision making is discussed
      to optimize the provision of stroke rehabilitation services.

PMID- 22975744
TI  - Nuclei of the human raphe.
AB  - Along the raphe of the brain stem, a series of small neuronal groups can be
      observed in the medulla oblongata, the pons and the mesencephalon. The neurons
      located in and adjacent to the raphe are considered to produce mainly serotonin
      (5-HT). The groups of nuclei containing 5-HT were first reported in experimental
      animals in the early 1960s. The presence of such nuclei, however, has not yet
      been brought to light in the human brainstem except the few atlases, although in
      several neuroanatomy textbooks, extrapolated data are shown in the form of
      drawings as if they were the data from the human brain. The aim of this study is
      to present microscopic photos of such raphe nuclei made from serial sections of
      the human brainstem, and to clarify the differences between findings in human and
      textbook drawings from animal data.

PMID- 22975745
TI  - Evaluation of the spinal cord white matter.
AB  - Morphological findings or evaluations of the nervous system have traditionally
      concentrated on cell somata; evaluations of the white matter have not been put
      forward up to now. This study was conducted to evaluate the white matter in the
      spinal cord with the LPH discriminative staining method which was proposed by
      Goto. Thanks to the minimum shrinkage ratio (10 +/- 0% in length) which this
      technique allows, it is possible to evaluate the sizes of nerve axons, and to
      compare the arrangement of nerve fibers in various parts of the spinal white
      matter. As the axonal sizes reflect nerve conduction velocities, we would like to
      emphasize that these sizes or the differences in the arrangement of axons may be
      important for a better understanding of neurosymptomatology.

PMID- 22975746
TI  - The value of the wechsler intelligence scale for children-fourth edition digit
      span as an embedded measure of effort: an investigation into children with dual
      diagnoses.
AB  - The Test of Memory Malingering (TOMM) is a measure of test-taking effort which
      has traditionally been utilized with adults, but which more recently has
      demonstrated utility with children. The purpose of this study was to investigate
      whether the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV)
      Digit Span, commonly used in neuropsychological evaluations, can also be
      functional as an embedded measure by detecting effort in children with dual
      diagnoses; a population yet to be investigated. Participants (n = 51) who
      completed neuropsychological evaluations including the TOMM, WISC-IV, Wisconsin
      Card Sorting Test, Children's Memory Scale, and Delis-Kaplan Executive Function
      System were divided into two groups: Optimal Effort and Suboptimal Effort, based
      on their TOMM Trial 2 scores. Digit Span findings suggest a useful scaled score
      of <=4 resulted in optimal cutoff scores, yielding specificity of 91% and
      sensitivity of 43%. This study supports previous research that the WISC-IV Digit
      Span has good utility in determining optimal effort, even in children with dual
      diagnosis or comorbidities.

PMID- 22975747
TI  - Layered mass geometry: a novel technique to overlay seeds and applicators onto
      patient geometry in Geant4 brachytherapy simulations.
AB  - A problem faced by all Monte Carlo (MC) particle transport codes is how to handle
      overlapping geometries. The Geant4 MC toolkit allows the user to create parallel
      geometries within a single application. In Geant4 the standard mass-containing
      geometry is defined in a simulation volume called the World Volume. Separate
      parallel geometries can be defined in parallel worlds, that is, alternate three
      dimensional simulation volumes that share the same coordinate system with the
      World Volume for geometrical event biasing, scoring of radiation interactions,
      and/or the creation of hits in detailed readout structures. Until recently, only
      one of those worlds could contain mass so these parallel worlds provided no
      solution to simplify a complex geometric overlay issue in brachytherapy, namely
      the overlap of radiation sources and applicators with a CT based patient
      geometry. The standard method to handle seed and applicator overlay in MC
      requires removing CT voxels whose boundaries would intersect sources, placing the
      sources into the resulting void and then backfilling the remaining space of the
      void with a relevant material. The backfilling process may degrade the accuracy
      of patient representation, and the geometrical complexity of the technique
      precludes using fast and memory-efficient coding techniques that have been
      developed for regular voxel geometries. The patient must be represented by the
      less memory and CPU-efficient Geant4 voxel placement technique, G4PVPlacement,
      rather than the more efficient G4NestedParameterization (G4NestedParam). We
      introduce for the first time a Geant4 feature developed to solve this issue:
      Layered Mass Geometry (LMG) whereby both the standard (CT based patient geometry)
      and the parallel world (seeds and applicators) may now have mass. For any area
      where mass is present in the parallel world, the parallel mass is used.
      Elsewhere, the mass of the standard world is used. With LMG the user no longer
      needs to remove patient CT voxels that would include for example seeds. The
      patient representation can be a regular voxel grid, conducive to G4NestedParam,
      and the patient CT derived materials remain exact, avoiding the inaccuracy of the
      backfilling technique. Post-implant dosimetry for one patient with (125)I
      permanent seed implant was performed using Geant4 version 9.5.p01 using three
      different geometrical techniques. The first technique was the standard described
      above (G4PVPlacement). The second technique placed patient voxels as before, but
      placed seeds with LMG (G4PVPlacement+LMG). The third technique placed patient
      voxels through G4NestedParam and seeds through LMG (G4NestedParam+LMG). All the
      scenarios were calculated with 3 different image compression factors to
      manipulate the number of voxels. Additionally, the dosimetric impact of the
      backfilling technique was investigated for the case of calcifications in close
      proximity of sources. LMG eliminated the need for backfilling and simplified
      geometry description. Of the two LMG techniques, G4PVPlacement+LMG had no benefit
      to calculation time or memory use, actually increasing calculation time, but
      G4NestedParam+LMG reduced both calculation time and memory. The benefits of
      G4NestedParam+LMG over standard G4PVPlacement increased with increasing voxel
      numbers. For the case of calcifications in close proximity to sources, LMG not
      only increased efficiency but also yielded more accurate dose calculation than
      G4PVPlacement. G4NestedParam in combination with LMG present a new, efficient
      approach to simulate radiation sources that overlap patient geometry. Cases with
      brachytherapy applicators would constitute a direct extension of the method.

PMID- 22975749
TI  - Rapidly progressive dementia as presenting feature in inflammatory bowel disease.

PMID- 22975750
TI  - Involvement in activities and wandering in nursing home residents with cognitive
      impairment.
AB  - OBJECTIVES: Analysis of a relationship between wandering and involvement in
      meaningful activities in nursing home residents with cognitive impairment.
      DESIGN: Cross-sectional analysis of the minimum data set information. SETTING:
      The analyses were conducted on 8 nursing homes in the Netherlands. PARTICIPANTS:
      The participants were residents aged 65 years and above with an evidence of
      cognitive impairment. MEASUREMENTS: Items in the minimum data set related to
      wandering behavior, involvement in activities, presence of psychotic symptoms,
      and treatment with antipsychotics. Ambulatory residents who exhibited wandering
      were divided into: those whose behavior was easily altered [modifiable wandering
      (MW)] and those whose wandering behavior was not easily altered by the staff
      [nonmodifiable wandering (NMW)]. The duration of time for which they had
      opportunity to be involved in meaningful activities was estimated from
      involvement in activities of nonambulatory residents. RESULTS: The prevalence of
      wandering increased with severity of cognitive impairment. MW was present in 3.5%
      of total residents (8.5% of ambulatory), whereas NMW was present in 11.2% of the
      total ambulatory and nonambulatory residents (26.6% of ambulatory). The risk of
      NMW was increased with resistiveness to care and decreased with antipsychotic
      use. Individuals with NMW were less involved in activities. NMW was more
      prevalent in facilities in which residents were involved in activities for a
      shorter duration. CONCLUSIONS: Involvement of residents in meaningful activities
      should be tested for reducing the incidence of problematic wandering and for
      decrease in usage of antipsychotic medications.

PMID- 22975751
TI  - Association of GWAS top hits with late-onset Alzheimer disease in Korean
      population.
AB  - Recent genome-wide association studies (GWAS) have discovered several Alzheimer
      disease (AD) susceptibility loci. However, the identified susceptibility loci are
      substantially inconsistent across GWAS. We aimed to investigate the association
      of top associated variants in GWAS with AD in Korean population. We selected 86
      single-nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1,
      CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) and genotyped in
      290 AD cases and 554 unrelated controls from the same region. Three SNPs
      [rs429358 in APOE: odds ratio (OR)=4.24, 95% confidence interval (CI)=3.01-5.96,
      P=1.23*10; rs2075650 in APOE: OR=3.57, 95% CI=2.51-5.06, P=1.23*10; and rs677909
      in PICALM: OR=0.63, 95% CI=0.49-0.81, P=0.00036, log additive model] were
      significantly associated with AD susceptibility after correction for multiple
      testing. Six additional PICALM SNPs, 3 ABCA7 SNPs, and 1 APOE, CD33, and BIN1
      SNPs each had significant uncorrected P values. There was no significant
      association for age at onset of AD. Our results confirm the association of PICALM
      gene (encoding phosphatidylinositol-binding protein) in addition to APOE gene
      with AD susceptibility in Korean population but did not show significant
      associations of other susceptibility loci with AD. 

PMID- 22975752
TI  - You can't always get what you want, but if you try sometimes (with two tests--TST
      and IGRA--for tuberculosis) you get what you need.

PMID- 22975754
TI  - A merged presentation of clinical and radiographic data using probability plots
      in a clinical trial, the JESMR study.

PMID- 22975753
TI  - Serum proteins reflecting inflammation, injury and repair as biomarkers of
      disease activity in ANCA-associated vasculitis.
AB  - OBJECTIVE: To identify circulating proteins that distinguish between active anti
      neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission
      in a manner complementary to markers of systemic inflammation. METHODS: Twenty
      eight serum proteins representing diverse aspects of the biology of AAV were
      measured before and 6 months after treatment in a large clinical trial of AAV.
      Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE)
      trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) levels were available for comparison. The primary outcome was the ability
      of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for
      Wegener's granulomatosis (BVAS/WG)>=3 at screening) from remission (BVAS/WG=0 at
      month 6), using areas under receiver operating characteristic (ROC) curve (AUC).
      RESULTS: All subjects had severe active vasculitis (median BVAS/WG=8) at
      screening. In the 137 subjects in remission at month 6, 24 of the 28 markers
      showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA
      1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases
      1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from
      healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP
      were low. CONCLUSIONS: Many markers are elevated in severe active AAV and decline
      with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from
      remission better than the other markers studied, including ESR and CRP. These
      proteins are particularly promising candidates for future studies to address
      unmet needs in the assessment of patients with AAV.

PMID- 22975755
TI  - Markers of inflammation and bone remodelling associated with improvement in
      clinical response measures in psoriatic arthritis patients treated with
      golimumab.
AB  - OBJECTIVE: To determine serum biomarker associations with clinical response to
      golimumab treatment in patients with psoriatic arthritis (PsA). METHODS: GO
      REVEAL was a randomised, placebo-controlled study of golimumab in patients with
      active PsA. Samples were collected from 100 patients at baseline, week 4 and week
      14, and analysed for serum-based biomarkers and protein profiling (total 92
      markers); data were correlated with clinical measures at week 14. RESULTS: Serum
      levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16,
      myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix
      metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen,
      intercellular adhesion molecule 1 and macrophage inflammatory protein 1alpha) at
      baseline or week 4 were strongly associated with American College of Rheumatology
      20% improvement (ACR20) response and/or disease activity score in 28 joints
      (DAS28) at week 14. A smaller subset of proteins was significantly associated
      with a 75% improvement in the psoriasis area and severity index score (PASI75) at
      week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic
      transaminase, and tumour necrosis factor alpha). Subsets of proteins were
      identified as potentially predictive of clinical response for each of the
      clinical measures, and the power of these biomarker panels to predict clinical
      response to golimumab treatment was stronger than for CRP alone. CONCLUSIONS:
      This analysis provides insight into several panels of markers that may have
      utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75
      responses following golimumab treatment.

PMID- 22975757
TI  - Stereogenic metal centres - from Werner to supramolecular chemistry.
AB  - Chirality is a concept that lies at the heart of organic chemistry but is often
      ignored in discussions of inorganic systems. This omission is all the more
      surprising, given the seminal role played by the study of chiral systems in the
      development of coordination chemistry. This tutorial review gives a brief
      introduction to the concept of chirality in coordination and supramolecular
      compounds for the non-specialist.

PMID- 22975756
TI  - Autophagy regulates TNFalpha-mediated joint destruction in experimental
      arthritis.
AB  - OBJECTIVES: Autophagy is a homeostatic process to recycle dispensable and damaged
      cell organelles. Dysregulation of autophagic pathways has recently been
      implicated in the pathogenesis of various diseases. Here, we investigated the
      role of autophagy during joint destruction in arthritis. METHODS: Autophagy in
      osteoclasts was analysed in vitro and ex vivo by transmission electron
      microscopy, Western blotting and immunohistochemistry for Beclin1 and Atg7. Small
      molecule inhibitors, LysMCre-mediated knockout of Atg7 and lentiviral
      overexpression of Beclin1 were used to modulate autophagy in vitro and in vivo.
      Osteoclast differentiation markers were quantified by real-time PCR. The extent
      of bone and cartilage destruction was analysed in human tumour necrosis factor
      alpha transgenic (hTNFalpha tg) mice after adoptive transfer with myeloid
      specific Atg7-deficient bone marrow. RESULTS: Autophagy was activated in
      osteoclasts of human rheumatoid arthritis (RA) showing increased expression of
      Beclin1 and Atg7. TNFalpha potently induced the expression of autophagy-related
      genes and activated autophagy in vitro and in vivo. Activation of autophagy by
      overexpression of Beclin1-induced osteoclastogenesis and enhanced the resorptive
      capacity of cultured osteoclasts, whereas pharmacologic or genetic inactivation
      of autophagy prevented osteoclast differentiation. Arthritic hTNFalpha tg mice
      transplanted with Atg7(fl/fl)*LysMCre(+) bone marrow cells (BMC) showed reduced
      numbers of osteoclasts and were protected from TNFalpha-induced bone erosion,
      proteoglycan loss and chondrocyte death. CONCLUSIONS: These findings demonstrate
      that autophagy is activated in RA in a TNFalpha-dependent manner and regulates
      osteoclast differentiation and bone resorption. We thus provide evidence for a
      central role of autophagy in joint destruction in RA.

PMID- 22975758
TI  - Improving mutation notification when new genetic information is identified in
      research: a trial of two strategies in familial breast cancer.
AB  - PURPOSE: The Kathleen Cuningham Foundation Consortium for Research into Familial
      Aspects of Breast Cancer (kConFab) is a large-scale research study that notifies
      participants when new, personally relevant, information is discovered. In 2009,
      the (kConFab) instituted an intensive notification process to ensure at-risk
      individuals were effectively notified. This study (i) evaluated the impact of
      intensive notification on genetic testing uptake; (ii) identified those most
      likely to undergo testing postnotification; and (iii) identified those most
      likely to acknowledge that they had been notified. METHODS: Clinical/demographic
      data were retrieved from the (kConFab) database. Logistic regression analyses
      were conducted to identify potential predictors of testing uptake and
      notification acknowledgment using IBM SPSS. RESULTS: A total of 155 of 1,812
      individuals underwent testing after standard notification (8.6%). In comparison,
      23/291 individuals (7.9%) notified using the "intensive" approach underwent
      testing (chi(2) = 0.14; P = 0.71). After controlling for notification process,
      females and participants with a previous cancer were most likely to have
      undergone testing (P < 0.006). Older individuals (50+ years) were most likely to
      acknowledge they had been notified (P = 0.038). CONCLUSION: Increasing the
      intensity of participant follow-up did not increase genetic testing uptake. The
      challenge to effectively notify participants, and increase the proportion whose
      risk is managed clinically, remains, particularly for males and individuals
      unaffected by cancer.Genet Med 2013:15(3):187-194.

PMID- 22975759
TI  - Informatics and clinical genome sequencing: opening the black box.
AB  - Adoption of whole-genome sequencing as a routine biomedical tool is dependent not
      only on the availability of new high-throughput sequencing technologies, but also
      on the concomitant development of methods and tools for data collection,
      analysis, and interpretation. It would also be enormously facilitated by the
      development of decision support systems for clinicians and consideration of how
      such information can best be incorporated into care pathways. Here we present an
      overview of the data analysis and interpretation pipeline, the wider informatics
      needs, and some of the relevant ethical and legal issues.

PMID- 22975760
TI  - An empirical estimate of carrier frequencies for 400+ causal Mendelian variants:
      results from an ethnically diverse clinical sample of 23,453 individuals.
AB  - PURPOSE: Recent developments in genomics have led to expanded carrier screening
      panels capable of assessing hundreds of causal mutations for genetic disease.
      This new technology enables simultaneous measurement of carrier frequencies for
      many diseases. As the resultant rank-ordering of carrier frequencies impacts the
      design and prioritization of screening programs, the accuracy of this ranking is
      a public health concern. METHODS: A total of 23,453 individuals from many
      obstetric, genetics, and infertility clinics were referred for routine recessive
      disease carrier screening. Multiplex carrier screening was performed and results
      were aggregated for this study. RESULTS: Twenty-four percent of individuals were
      identified as carriers for at least one of 108 disorders, and 5.2% were carriers
      for multiple disorders. We report tabulations of carrier frequency by self
      identified ethnicity and disease. CONCLUSION: To our knowledge, this study of a
      large, ethnically diverse clinical sample provides the most accurate measurements
      to date of carrier frequencies for hundreds of recessive alleles. The study also
      yields information on the clinical considerations associated with routine use of
      expanded panels and provides support for a pan-ethnic screening paradigm that
      minimizes the use of "racial" categories by the physician, as recommended by
      recent guidelines.

PMID- 22975761
TI  - Cost-effectiveness of the 21-gene recurrence score assay in the context of
      multifactorial decision making to guide chemotherapy for early-stage breast
      cancer.
AB  - PURPOSE: New evidence is available regarding the utility of the 21-gene
      recurrence score assay in guiding chemotherapy use for node-negative, estrogen
      receptor-positive breast cancer. We applied this evidence in a decision-analytic
      model to re-evaluate the cost-effectiveness of the assay. METHODS: We cross
      classified patients by clinicopathologic characteristics from the Adjuvant! risk
      index and by recurrence score risk group. For non-recurrence score-guided
      treatment, we assumed patients receiving hormonal therapy alone had low-risk
      characteristics and patients receiving chemotherapy and hormonal therapy had
      higher-risk characteristics. For recurrence score-guided treatment, we assigned
      chemotherapy probabilities conditional on recurrence score risk group and
      clinicopathologic characteristics. RESULTS: An estimated 40.4% of patients in the
      recurrence score-guided strategy and 47.3% in the non-recurrence score-guided
      strategy were expected to receive chemotherapy. The incremental gain in quality
      adjusted life-years was 0.16 (95% confidence interval, 0.08-0.28) with the
      recurrence score-guided strategy. Lifetime medical costs to the health system
      were $2,692 ($1,546-$3,821) higher with the recurrence score-guided strategy, for
      an incremental cost-effectiveness ratio of $16,677/quality-adjusted life-year
      ($7,613-$37,219). From a societal perspective, the incremental cost-effectiveness
      was $10,788/quality-adjusted life-year ($6,840-$30,265). CONCLUSION: The findings
      provide supportive evidence for the economic value of the 21-gene recurrence
      score assay in node-negative, estrogen receptor-positive breast cancer.

PMID- 22975762
TI  - Salt-mediated kinetics of the self-assembly of gold nanorods end-tethered with
      polymer ligands.
AB  - Studies on the self-assembly of metal nanoparticles (NPs) in the presence of ions
      are motivated by the biosensing applications of NP clusters and the capability to
      control the morphology of clusters of oppositely charged NPs. The effect of ions
      has been explored for the self-assembly of metal NPs capped solely with ionic
      ligands, whereas, in general, the surface of NPs can be coated with a mixture of
      ligands interacting with each other by non-electrostatic forces. In the present
      work, we examined the kinetics of self-assembly of gold nanorods capped with a
      mixture of low-molecular weight ionic molecules and nonpolar polymer ligands. We
      show that in contrast with earlier reports on the effect of electrolytes on NP
      self-assembly, the driving force for the accelerated self-assembly of nanorods is
      the reduction in polymer solubility in the presence of ions, rather than the
      screening of the electric double layer of the charged ligands. The reported
      results are important for NP self-assembly occurring in mixed solvents, in which
      attraction forces between nonpolar ligands are governed by the balance between
      solvent-solvent and solvent-salt interactions. Furthermore, the addition of salts
      can be used to increase the rate of nanorod self-assembly, which, otherwise, is
      an intrinsically slow process.

PMID- 22975763
TI  - Boceprevir: a protease inhibitor for the treatment of hepatitis C.
AB  - BACKGROUND: Boceprevir is a protease inhibitor indicated for the treatment of
      chronic hepatitis C virus (HCV) genotype 1 infection in combination with
      peginterferon and ribavirin for treatment-naive patients and those who previously
      failed to improve with interferon and ribavirin treatment. OBJECTIVE: This
      article provides an overview of the mechanism of action, pharmacologic and
      pharmacokinetic properties, clinical efficacy, and tolerability of boceprevir.
      METHODS: Relevant information was identified through a search of PubMed (1990
      July 2012), EMBASE (1990-July 2012), International Pharmaceutical Abstracts (1970
      July 2012), and Google Scholar using the key words boceprevir, SCH 503034, non
      structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral
      agent (DAA). Additional information was obtained from the US Food and Drug
      Administration's Web site, review of the reference lists of identified articles,
      and posters and abstracts from scientific meetings. RESULTS: Clinical efficacy of
      boceprevir was assessed in 2 Phase III trials, Serine Protease Inhibitor Therapy
      2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV Serine
      Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment
      experienced patients. In SPRINT-2, patients were randomized to receive
      peginterferon + ribavirin (PR) or peginterferon + ribavirin + boceprevir (PRB);
      duration of boceprevir therapy varied from 24, 32, to 44 weeks on the basis of
      HCV RNA results. The primary endpoint was achievement of sustained virologic
      response (SVR; lower limit of detection, 9.3 IU/mL). The addition of boceprevir
      was shown to be superior, with overall SVR rates ranging from 63% to 66% compared
      with 38% with PR (P < 0.001). Results of SVR in SPRINT-2 were also reorganized to
      monitor SVRs in black and non-black patients. Treatment-experienced patients were
      assessed in RESPOND-2; however, null responders were excluded. Patients were
      again randomized to PR or PRB; duration of boceprevir therapy varied from 32 to
      44 weeks on the basis of HCV RNA results. SVR was significantly higher in
      patients receiving boceprevir (59%-66% vs 21% with PR; P < 0.001). This benefit
      was seen in both previous nonresponders (SVR, 40%-52% vs 7% with PR), as well as
      previous relapsers (SVR, 69%-75% vs 29% with PR). Importantly, SVR could be
      attained with a shortened course of therapy in almost one half of all treated
      patients in SPRINT-2 (44%) and RESPOND-2 (46%). CONCLUSIONS: Boceprevir was well
      tolerated in clinical trials and a welcomed addition to our HCV armamentarium.

PMID- 22975764
TI  - Five-year follow-up of 16 melanoma patients with a Starz I-involved sentinel node
      in whom completion lymph node dissection was omitted.
AB  - The aim of the study was to determine the incidence of lymph node recurrence in
      16 melanoma patients with a minimal metastasis (Starz level I) in a sentinel node
      in whom a completion lymph node dissection was omitted. A secondary aim was to
      examine whether other melanoma-related recurrences developed. Sixteen melanoma
      patients with an SI-involved sentinel node, who did not undergo completion lymph
      node dissection, were followed for a median of 66 months. Lymph node recurrences
      did not occur. One of the 16 patients developed a local recurrence and another
      developed satellite metastases. None of the 16 patients with an SI-positive
      sentinel node developed a nodal recurrence, which suggests that the risk of
      refraining from node dissection in such patients is small. This option could be
      considered and discussed with the patient in terms of the risk of nonsentinel
      node involvement and the unsolved problem of unknown overall survival advantage.

PMID- 22975765
TI  - [Immunologically escaped hematopoiesis caused by HLA allelic loss in patients
      with aplastic anemia].

PMID- 22975766
TI  - [Novel therapeutic strategy for hematological diseases using iPS cell-banking].

PMID- 22975767
TI  - [Molecular mechanism of granule secretion from platelet].

PMID- 22975768
TI  - [Advances in ADAMTS13 research].

PMID- 22975769
TI  - [Fibrinolytic system regulates hematopoietic cell differentiation and
      recruitment].

PMID- 22975771
TI  - [Survey on examinations for diagnosis of bone marrow failure in Japan: a report
      from the Japanese National Research Group on Idiopathic Bone Marrow Failure
      Syndromes].
AB  - Using a registration sheet of a prospective registration system for aplastic
      anemia (AA)/myelodysplastic syndromes (MDS), by the National Research Group on
      Idiopathic Bone Marrow Failure Syndromes, Japan, we carried out a survey on
      examinations for diagnosis of bone marrow failure. Bone marrow trephine biopsy
      was performed in 66 of 105 cases (63%) [Original diagnosis: AA 51 cases (80%),
      MDS 12 (32%), undiagnosable 3 (75%)]. Bone marrow aspiration was performed in all
      cases, and aspiration was performed at least twice in 36 cases (34%). The first
      line anatomic site for bone marrow aspiration was the posterior iliac crest
      (62%). Cytogenetic examination was performed in 93%. The concordance rate between
      the original and the central review diagnosis was 93% among the studied cases:
      AA, Idiopathic cytopenia of undetermined significance (ICUS) and MDS in total.
      Flow cytometry analysis to detect paroxysmal nocturnal hemoglobinuria (PNH)-type
      blood cells was performed in 32%.

PMID- 22975770
TI  - [Efficacy and safety of piperacillin-tazobactam for febrile neutropenic patients
      in Japan].
AB  - The IDSA guideline for management of febrile neutropenic patients updated in 2010
      recommends monotherapy with anti-pseudomonal-lactam agents, including
      piperacillin-tazobactam (PIPC/TAZ) for high-risk patients. However, clinical
      studies of PIPC/TAZ are limited in Japanese patients. In this study, we conducted
      an open-labeled non-randomized prospective trial to examine the efficacy and
      safety of PIPC/TAZ as an empirical treatment for Japanese patients with febrile
      neutropenia. Forty-nine febrile episodes in neutropenic patients excluding those
      undergoing allogeneic stem cell transplantation (high risk 36, low risk 13) were
      analyzed. The overall response rate was 71%, and no significant differences
      between the high-risk and the low-risk group were observed (high risk 72%, low
      risk 69%). Neither PS nor usage of G-CSF affected the response rate. No major
      side effects were observed in the study. The efficacy and the safety profile of
      PIPC/TAZ treatment were comparable to those in other previous Western studies. In
      conclusion, this study suggests PIPC/TAZ is effective and well tolerated as an
      initial empirical treatment for febrile neutropenic Japanese patients.

PMID- 22975772
TI  - [Retrospective analysis of treatment outcomes in 70 patients with t(8;21) acute
      myeloid leukemia].
AB  - We conducted a retrospective study to evaluate outcomes and prognostic factors of
      newly diagnosed patients with t(8;21) acute myeloid leukemia (AML). There were 70
      patients (43 men and 27 women) with a median age of 48 years old (range, 17~76
      years old). Sixty-five patients achieved complete remission (CR) after induction
      chemotherapy. Fifty-seven patients received consolidation chemotherapy based on
      the policy of not performing allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) at the time of first CR. Twenty-seven of the 57 patients relapsed
      (relapse rate, 47%). The median time from the achievement of the first CR to
      relapse was 307 days (96~1,256 days). A white blood cell count of more than
      25,400/MUl at diagnosis was associated with a higher relapse rate than a white
      blood cell count of less than or equal to 25,400/MUl (75% vs. 43%, P=0.04).
      Nineteen of the 25 relapsed patients who received re-induction therapy
      experienced a second CR (second CR rate, 76%). Twenty-six patients (5 with first
      CR, 12 with second CR, and 9 without remission) received allo-HSCT. The five-year
      overall survival and disease-free survival rates were 61% and 45%, respectively.
      Patients with t(8;21) AML had a high CR rate, but about half of them relapsed.
      However, this report could not show prognostic factors for the identification of
      patients who should receive allo-HSCT at the time of their first CR.

PMID- 22975773
TI  - [CD20-positive peripheral T-cell lymphoma, not otherwise specified].
AB  - We report a 69-year-old male with CD3-positive peripheral T-cell lymphoma, not
      otherwise specified (PTCL-nos). Interestingly, tumor cells slightly expressed
      CD20 as well. Southern analyses of the tumor cells showed rearrangement for only
      the T cell receptor gene but not the immunoglobulin genes. This patient achieved
      partial remission with a treatment regimen of THP-COP excluding prednisolone, but
      died of pneumonia. Although CD20-positive PTCL is rare, a review of the reported
      cases suggests that CD20-positive PTCL has a poor prognosis and that bone marrow
      infiltration of tumor cells results in a poorer prognosis in CD20-positive PTCL
      than in usual PTCL. By accumulating cases of this rare entity of lymphoma, we
      need to clarify the biological nature of the tumor cells and usefulness of
      rituximab combined with standard chemotherapy.

PMID- 22975774
TI  - [Clinical analysis of autologous stem cell transplantation for nine cases of
      cardiac amyloidosis].
AB  - Long-term survival remains poor for patients with cardiac amyloidosis. High-dose
      melphalan (MEL) with stem cell transplantation (HDM/SCT) is an effective
      treatment for AL amyloidosis, but patients with cardiac involvement are
      ineligible because of high therapy-related mortality. Here we report detailed
      HDM/SCT outcomes of 9 patients with cardiac failure. Their median age was 56
      years (range, 45~66). After a median follow-up of 15 months (range 9~32), three
      died of multiorgan failure within the early phase after HDM/SCT, and the other
      six including poor risk patients are alive at present. Their symptoms of cardiac
      decompensation have improved. Decreases in interventricular septum thickness were
      confirmed in 4 patients 6~12 months after HDM/SCT by echocardiography. One-year
      overall survival rate was 67%, longer than previously reported rates. HDM/SCT may
      lead to improvements in quality of life and extended survival in cardiac
      amyloidosis patients. Meanwhile, the median dosage of MEL in our procedure was
      103 mg/m(2) (range 68~180), less than the recommended dose, and patients were
      maintained on miscellaneous therapies. Further studies are required to clarify an
      effective MEL dose and to refine selection criteria for patients undergoing
      HDM/SCT.

PMID- 22975775
TI  - [Lupus anticoagulant-hypoprothrombinemia syndrome with a false-positive test for
      coagulation factor inhibitors].
AB  - We report a case of a 1-year-old boy diagnosed with lupus anticoagulant
      hypoprothrombinemia syndrome (LA-HPS), which is a rare disorder. His initial
      presentation of sinusitis was accompanied by hemorrhagic episodes including
      ecchymoses and epistaxis 6 months after antibiotic therapy. Laboratory results
      revealed prolonged prothrombin time (PT) and activated partial thromboplastin
      time (APTT) that did not correct with mixing studies. Factors II, VIII, IX, X,
      XI, and XII activities were 20%, 44%, 42.5%, 59%, 4%, and 10%, respectively. The
      Bethesda inhibitor assay showed inhibitors against multiple coagulation factor.
      APTT, mixing studies, diluted Russell's viper venom time, and the Bethesda
      inhibitor assay detected LA. LA-HPS with a suspected false-positive test for
      coagulation factor inhibitors was diagnosed. Bleeding stopped and results of
      coagulation studies returned to normal without therapy 2 months after onset of
      the disease.

PMID- 22975776
TI  - Advancing science and policy through a coordinated international study of
      physical activity and built environments: IPEN adult methods.
AB  - BACKGROUND: National and international strategies to increase physical activity
      emphasize environmental and policy changes that can have widespread and long
      lasting impact. Evidence from multiple countries using comparable methods is
      required to strengthen the evidence base for such initiatives. Because some
      environment and policy changes could have generalizable effects and others may
      depend on each country's context, only international studies using comparable
      methods can identify the relevant differences. METHODS: Currently 12 countries
      are participating in the International Physical Activity and the Environment
      Network (IPEN) study. The IPEN Adult study design involves recruiting adult
      participants from neighborhoods with wide variations in environmental walkability
      attributes and socioeconomic status (SES). RESULTS: Eleven of twelve countries
      are providing accelerometer data and 11 are providing GIS data. Current
      projections indicate that 14,119 participants will provide survey data on built
      environments and physical activity and 7145 are likely to provide objective data
      on both the independent and dependent variables. Though studies are highly
      comparable, some adaptations are required based on the local context&period;
      CONCLUSIONS&colon; This study was designed to inform evidence-based international
      and country-specific physical activity policies and interventions to help prevent
      obesity and other chronic diseases that are high in developed countries and
      growing rapidly in developing countries.

PMID- 22975777
TI  - The association between individual income and remaining life expectancy at the
      age of 65 in the Netherlands.
AB  - This article quantifies the association between individual income and remaining
      life expectancy at the statutory retirement age (65) in the Netherlands. For this
      purpose, we estimate a mortality risk model using a large administrative data set
      that covers the 1996-2007 period. Besides age and marital status, the model
      includes as covariates individual and spouse's income as well as a random
      individual specific effect. It thus allows for dynamic selection based on both
      observed and unobserved characteristics. We find that conditional on marital
      status, individual income is about equally strong and negatively associated with
      mortality risk for men and women and that spouse's income is only weakly
      associated with mortality risk for women. For both men and women, we quantify
      remaining life expectancy at age 65 for low-income individuals as approximately
      2.5 years less than that for high-income individuals.

PMID- 22975778
TI  - Fast GPU-based computation of the sensitivity matrix for a PET list-mode OSEM
      algorithm.
AB  - During the last decade, studies have shown that 3D list-mode ordered-subset
      expectation-maximization (LM-OSEM) algorithms for positron emission tomography
      (PET) reconstruction could be effectively computed and considerably accelerated
      by graphics processing unit (GPU) devices. However, most of these studies rely on
      pre-calculated sensitivity matrices. In many cases, the time required to compute
      this matrix can be longer than the reconstruction time itself. In fact, the
      relatively long time required for the calculation of the patient-specific
      sensitivity matrix is considered as one of the main obstacle in introducing a
      list-mode PET reconstruction algorithm for routine clinical use. The objective of
      this work is to accelerate a fully 3D LM-OSEM algorithm, including the
      calculation of the sensitivity matrix that accounts for the patient-specific
      attenuation and normalization corrections. For this purpose, sensitivity matrix
      calculations and list-mode OSEM reconstructions were implemented on GPUs, using
      the geometry of a commercial PET system. The system matrices were built on-the
      fly by using an approach with multiple rays per detector pair. The
      reconstructions were performed for a volume of 188 * 188 * 57 voxels of 2 * 2 *
      3.15 mm(3) and for another volume of 144 * 144 * 57 voxels of 4 * 4 * 3.15 mm(3).
      The time to compute the sensitivity matrix for the 188 * 188 * 57 array was 9 s
      while the LM-OSEM algorithm performed at a rate of 1.1 millions of events per
      second. For the 144 * 144 * 57 array, the respective numbers are 8 s for the
      sensitivity matrix and 0.8 million of events per second for the LM-OSEM step.
      This work lets envision fast reconstructions for advanced PET applications such
      as real time dynamic studies and parametric image reconstructions.

PMID- 22975779
TI  - Antioxidant characteristics of extracts from cereal residues by their subcritical
      water treatment.
AB  - Subcritical water treatment of cereal residues including okara, defatted rice
      bran, desalted soy sauce lees, sake lees, corn kernel hull, and defatted rapeseed
      was conducted at 260 degrees C for 5 min to obtain the antioxidative extracts.
      The antioxidative activities of the extracts were evaluated using DPPH radical,
      peroxyl radical, hydroxyl radical, hypochlorite ion, and peroxynitrite ion. The
      results show that the extracts from the sake lees, corn kernel hull, and defatted
      rapeseed had differently the antioxidative activities against all radicals and
      ions. However, the okara, defatted rice bran and desalted soy sauce lees had no
      activity against the hypochlorite ion.

PMID- 22975780
TI  - Immobilization of Candida rugosa lipase on MCM-41 for the transesterification of
      cotton seed oil.
AB  - Present study demonstrated the preparation of MCM-41 as a support for the
      immobilization of Candida rugosa lipase by the physical adsorption technique. The
      lipase immobilized MCM-41 has been characterized by scanning electron microscopic
      and FTIR techniques. At pH 6, maximum lipase immobilization (250 mg/g) on MCM
      support has been observed and the immobilized lipase was employed as biocatalyst
      for the transesterification of the cotton seed oil with methanol. The pH of the
      reaction medium, reaction temperature and methanol/oil molar ratio have been
      optimized to achieve a maximum 98+/-3% fatty acid methyl esters yield (FAMEs)from
      cotton seed oil.

PMID- 22975781
TI  - Edible liquid marbles and capsules covered with lipid crystals.
AB  - Liquid marbles are water droplets covered with solid particles. Here we show a
      method for the preparation of edible liquid marbles and capsules covered with
      fatty acid crystals and triacylglycerol crystals. We prepared liquid marbles
      using a simple method; namely, a water droplet was rolled on lipid crystals in
      petri dishes. The resulting marbles were converted to capsules covered with a
      lipid shell by heating. These marbles were stable not only on glass surfaces but
      also on water surfaces because they had rigid hydrophobic exteriors. The lifetime
      of the liquid marbles on water depended on the alkyl chain length of the lipid
      molecules and the pH of the water. These findings are useful for applying liquid
      marbles to food, cosmetic, and medical products.

PMID- 22975782
TI  - Preparing glabridin-in-water nanoemulsions by high pressure homogenization with
      response surface methodology.
AB  - Glabridin is a pharmacological active hydrophobic pyranoisoflavan isolated from
      licorice. It has low bioavailability and solubility and therefore is difficult to
      apply for industry use. We investigated the effect of combining caprylic
      triglyceride with glabridin (2-6%, w/w), emulsifier (3-7%, w/w), and
      homogenization pressure (70-130 MPa) on the droplet size of glabridin
      nanoemulsions using response surface methodology by a 3-factor-3-level Box
      Behnken design. Oil content, emulsifier content and pressure had a significant
      effect on droplet size (p < 0.05). The optimal conditions for preparing glabridin
      nanoemulsions were predicted to be caprylic triglyceride (oil content), 3.7%;
      emulsifier content, 5.3%, and homogenization pressure, 129 MPa.

PMID- 22975783
TI  - Conjugated linoleic acids inhibit hypoxia inducible factor-1alpha stabilization
      under hypoxic condition in human hepatocellular carcinoma cells.
AB  - The anti-cancer effects of various fatty acids are drawing a lot of attention. To
      determine whether different fatty acids affect the hypoxic response of liver
      cancer cells, we examined the effects of various fatty acids on the stabilization
      of the hypoxia-inducible factor (HIF)-1alpha protein in the HepG2 human
      hepatocellular carcinoma (HCC) cell line under condition containing 1% O(2). Of
      the fatty acids examined, only 9cis, 11trans (c9, t11)-conjugated linoleic acid
      (CLA) and 10trans, 12cis (t10, c12)-CLA inhibited hypoxia-induced HIF-1alpha
      stabilization. In addition, HIF-1alpha prolyl hydroxylase or proteasome
      inhibition abrogated the effects of c9, t11- and t10, c12-CLA. Moreover, c9, t11-
      and t10, c12-CLA significantly inhibited cell proliferation and induced apoptotic
      cell death under hypoxia. This is the first study showing that c9, t11- and t10,
      c12-CLA inhibit the hypoxic response in HCC cells.

PMID- 22975784
TI  - Acid activated montmorillonite as catalysts in methyl esterification reactions of
      lauric acid.
AB  - The catalytic activity of acid activated montmorillonite in the esterification of
      free fatty acids (FFA) is reported. Standard Montmorillonite (MMT) type STx-1
      provided by the Clay Mineral Society repository was activated using phosphoric,
      nitric and sulphuric acids under different conditions and the resulting materials
      were characterized and evaluated as catalysts in the methyl esterification of
      lauric acid. Blank reactions carried out in the absence of any added catalyst
      presented conversions of 32.64, 69.79 and 79.23%, for alcohol:lauric acid molar
      ratios of 60:1, 12:1 and 6:1, respectively. In the presence of the untreated clay
      and using molar ratios of 12:1 and 6:1 with 12% of catalyst, conversions of 70.92
      and 82.30% were obtained, respectively. For the acid activated clays, conversions
      up to 93.08% of lauric acid to methyl laurate were obtained, much higher than
      those observed for the thermal conversion or using untreated montmorillonite.
      Relative good correlations were observed between the catalytic activity and the
      development of acid sites and textural properties of the resulting materials.
      Therefore, a simple acid activation was able to improve the catalytic activity
      and produce clay catalysts that are environmental friendly, cost effective,
      noncorrosive and reusable.

PMID- 22975785
TI  - Oxidative stability of glyceroglycolipids containing polyunsaturated fatty acids.
AB  - The oxidative stability of glyceroglycolipids (GLs) from spinach or brown edible
      seaweed (Laminaria japonica) was compared with those of phosphatidylcholines
      (PCs) from salmon roe and triacyglycerols (TAGs) from soybean oil or sardine oil.
      All the lipids were subjected to autoxidation after removing oxidants and/or
      antioxidants such as chlorophylls, tocopherols, and carotenoids. The oxidative
      stability of the lipids decreased with increasing number of bisallylic positions
      in the molecule. Due to the higher mean number of bisallylic positions, salmon
      roe PC and sardine oil TAG were oxidized more rapidly than soybean oil TAG.
      Spinach GL and brown edible seaweed GL showed the same oxidative stability as
      that found in soybean oil TAG, although the mean number of bisallylic positions
      of both GLs was much higher than that of soybean oil TAG and approached the
      number found in sardine oil TAG and salmon roe PC. The present study indicates
      the important effect of galactosyl and sulfoquinovosyl moieties on the oxidative
      stability of GL.

PMID- 22975786
TI  - Effect of caffeine and capsaicin on the blood glucose levels of obese/diabetic KK
      A(y) mice.
AB  - The present study is aimed to measure the effect of caffeine and capsaicin on the
      blood glucose level of obese/diabetic model mice. The blood glucose level of KK
      A(y) obese/diabetic mice decreased significantly after dietary supplementations
      with less than 0.031% caffeine and less than 0.0042% capsaicin, while both food
      ingredients and the combination had little effect on body weight gain and
      abdominal white adipose tissue (WAT) weight at this dose. The blood glucose level
      of the control mice was 234.4 mg/dL at 10 days after feeding and it increased to
      500.6 mg/dL after 28 days, while levels after intake of caffeine, capsaicin, and
      both together increased from 180, 131.6, and 140 mg/dL to 183.7, 255.1, and 151.6
      mg/dL, respectively. The anti-diabetic activity of caffeine and capsaicin was
      confirmed by a decrease in total drinking water and in the blood insulin level.

PMID- 22975788
TI  - Integrated immunology in Colorado.

PMID- 22975787
TI  - The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate
      immunity and inflammation.
AB  - TRPM2 (transient receptor potential melastatin 2) is the unique fusion of a
      Ca(2+)-permeable pore with an enzymatic domain that binds the NAD(+)-metabolite
      ADP-ribose (ADPR), resulting in channel opening. ADPR formation is a metabolic
      corollary of cellular stress, but can also be elicited enzymatically through NAD
      glycohydrolases like CD38. TRPM2 thus functions as a metabolic and oxidative
      stress sensor and translates this information into ion fluxes that can affect
      Ca(2+) signaling and the membrane potential. TRPM2 is strongly represented in
      immune cells of the phagocytic lineage, themselves professional generators of
      oxidants. The recent characterization of TRPM2-deficient mouse models has
      revealed the involvement of this channel in various aspects of immunity.
      Monocytes lacking TRPM2 show reduced production of the CXCL2 chemokine, resulting
      in diminished neutrophilic influx to the colon in chemically induced colitis, and
      thus protection against tissue ulceration in TRPM2(-/-) mice. However, the
      insufficient production of proinflammatory cytokines leads to high morbidity and
      lethality of the TRPM2(-/-) mice following infection with the bacterial pathogen
      Listeria monocytogenes. In the context of endotoxin-induced pulmonary
      inflammation, TRPM2's absence was found to promote inflammation and ROS
      production. TRPM2 acts thereby as a negative feedback loop by interfering through
      membrane depolarization with ROS generation by NADPH oxidases. In dendritic
      cells, TRPM2 is a lysosomal Ca(2+)-release channel that promotes chemokine
      responsiveness and cell migration, which is reminiscent of CD38-mediated
      functions. The discovery of TRPM2 has unveiled an unsuspected signaling pathway
      and established ADPR as a novel second messenger. Understanding TRPM2's complex
      involvement in inflammation is crucial to evaluating the potential of
      manipulating TRPM2 activity and ADPR metabolism for therapeutic intervention.

PMID- 22975789
TI  - Right heart assessment by echocardiography: gender and body size matters.
AB  - BACKGROUND: Published reference values for echocardiographic measurements of
      right-heart dimensions and function do not stratify for gender and body size. The
      aim of this study was therefore to assess the impact of gender and biometric
      characteristics on right-heart dimensions and function. METHODS: From the
      echocardiography database at a tertiary care center, 1,625 subjects (mean age, 44
      +/- 14 years; 47% men) with normal echocardiographic findings between 2000 and
      2009 were identified. Gender differences and association with body surface area
      were assessed retrospectively for right atrial long-axis and short-axis
      dimensions, right ventricular short-axis dimension, end-diastolic and end
      systolic right ventricular area, right ventricular fractional area change, and
      tricuspid annular plane systolic excursion. The impact of normal values
      stratified for gender and body surface area was tested in 24 patients with
      moderate-sized to large atrial septal defects. RESULTS: All dimensional right
      heart measurements were significantly lower in women. Differences became smaller
      when measurements were indexed for body surface area, but significant differences
      persisted, particularly for right ventricular end-diastolic area (7.9 +/- 1.6 vs
      8.7 +/- 1.8 cm(2)/m(2), P < .001) and right ventricular end-systolic area (4.0 +/
      1.2 vs 4.7 +/- 1.4 cm(2)/m(2), P < .001). Fractional area change and tricuspid
      annular plane systolic excursion indexed to body surface area were significantly
      higher in women (50 +/- 7% vs 46 +/- 9% and 14 +/- 3 vs 12 +/- 2 mm/m(2),
      respectively, P < .001 for both comparisons). The use of upper reference ranges
      for end-diastolic right ventricular area stratified for gender and body surface
      area improved the detection of enlarged right ventricles in patients with
      moderate-sized to large atrial septal defects (92% vs 54%, P < .007).
      CONCLUSIONS: Gender and body surface area are important determinants of right
      ventricular dimensions and systolic function as measured on two-dimensional
      echocardiography. The investigators thus propose the use of measurements indexed
      to body surface area, with upper and lower reference ranges stratified for
      gender.

PMID- 22975790
TI  - Echocardiographic evaluation of ventricular assist devices in pediatric patients.
AB  - BACKGROUND: The use of ventricular assist devices (VADs) in children is
      challenging because of small patient size, frequent structural heart disease, and
      the need for biventricular assist devices. This report describes the role of
      echocardiography in the management of children supported by VADs. METHODS: A
      retrospective review of the records of all pediatric patients who underwent VAD
      placement between May 2005 and May 2011 was performed to collect demographics,
      cardiac diagnoses, details of VADs, and transthoracic and transesophageal
      echocardiographic findings from the time of initial diagnosis until VAD
      explantation. RESULTS: The study included 32 patients (median age, 3 years; age
      range, 20 days to 16 years; median weight, 12.3 kg; weight range, 3.5-60 kg), 20
      with left ventricular assist devices and 12 with biventricular assist devices.
      Diagnoses included dilated cardiomyopathy or myocarditis (n = 27) and congenital
      heart disease (n = 5). The median duration of support was 12 days (range, 1-141
      days). Patients with decreased right ventricular function were 8 times more
      likely to undergo biventricular assist device placement compared with those with
      normal right ventricular function (P = .026). Pre-VAD intracardiac shunts were
      identified in 11 patients and intracardiac thrombus in one patient. Cardiac
      chamber dimensions and mitral insufficiency were significantly reduced after VAD
      implantation. Postimplantation pericardial effusions were recognized in 16
      patients and pericardial hematomas in 12 patients. CONCLUSIONS: Echocardiography
      is invaluable in the management of pediatric patients receiving VADs. It is
      helpful in pre-VAD assessment, guiding intraoperative device placement,
      recognizing VAD dysfunction, and identifying postimplantation complications.

PMID- 22975791
TI  - Single right ventricles have impaired systolic and diastolic function compared to
      those of left ventricular morphology.
AB  - BACKGROUND: Differences in single right ventricle (SRV) and single left
      ventricles (SLV) function are poorly described, although myocardial dysfunction
      is an important risk factor for morbidity and mortality. The aims of this study
      were to compare function between patients with SRVs and those with SLVs using
      newer echocardiographic techniques and to determine differences across staged
      palliation. METHODS: In this cross-sectional study comparing 30 patients with
      SRVs and 30 with SLVs of similar ages (2.5 +/- 1.7 vs 2.6 +/- 1.6 years),
      patients were matched for surgical stage (20 pre-bidirectional cavopulmonary
      anastomosis, 20 pre-Fontan, and 20 post-Fontan patients). Circumferential and
      longitudinal strain, strain rate (SR), early diastolic SR, postsystolic strain
      index, and myocardial dyssynchrony index were measured. Comparisons between SRV
      and SLV parameters were made as a whole group and by subanalysis at each surgical
      stage. RESULTS: Patients with SRVs had reduced systolic SRs (circumferential: 
      1.0%/sec vs -1.2%/sec, P = .01; longitudinal: -1.1%/sec vs -1.3%/sec, P = .002),
      reduced early diastolic SRs (circumferential: 1.4%/sec vs 1.9%/sec, P = .03;
      longitudinal: 1.6%/sec vs 2.2%/sec, P = .001), and increased circumferential
      postsystolic strain indexes (8% vs 0%, P < .0001). Subanalysis at each surgical
      stage showed that the greatest disparity in systolic parameters occurred before
      bidirectional cavopulmonary anastomosis (longitudinal SR, P = .009; postsystolic
      strain index, P = .005) and that parity was regained after the Fontan procedure,
      while traditional diastolic parameters (E velocity, P = .004; E/E' ratio, P =
      .0003) were reduced in patients with SRVs after the Fontan procedure.
      CONCLUSIONS: The SRV has reduced contractility and diastolic function compared
      with the SLV. Ventricular systolic performance in patients with SRVs was poorest
      before bidirectional cavopulmonary anastomosis, while differences in diastolic
      function were more prominent after Fontan completion.

PMID- 22975792
TI  - V(IV)O and Cu(II) complexation by ligands based on pyridine nitrogen donors.
AB  - The binary and ternary systems formed by V(IV)O and Cu(II) ions with ligands (L)
      based on the pyridine ring (1,10-phenanthroline (phen), 2,2'-bipyridine (bpy),
      2,2':6',2''-terpyridine (terpy), 2,2'-bipyrimidine (bpm) and 2,3-bis(2
      pyridyl)pyrazine (bpp)) were studied, combining spectroscopic (EPR and UV-vis),
      pH-potentiometric and computational (DFT calculations) methods. In the systems
      with V(IV)O, the formation of mono-chelated complexes with equatorial-equatorial
      and equatorial-axial (phen, bpy, bpm and bpp) or equatorial-equatorial-equatorial
      and equatorial-axial-equatorial coordination (terpy) and bis-chelated species
      with cis-octahedral geometry, with a water or a hydroxido ion in the fourth
      equatorial position, is demonstrated. Phen, bpy, bpm and bpp form also a
      dinuclear [(VO)(2)L(2)(H(2)O)(2)(OH)(2)](2+) complex with an anti-coplanar
      arrangement of the two V(IV)O ions and a ferromagnetic coupling between the metal
      ions. Due to the low basicity of the nitrogen donors, the potentially
      tetradentate 2,2'-bipyrimidine and 2,3-bis(2-pyridyl)pyrazine behave like simple
      bidentate ligands, and in the ternary systems with 2,2'-bipyridine the expected
      dinuclear species, in which the former ligands would act as a bridge between the
      two metal ions using all four nitrogen donors, are not formed. The interaction of
      phen and Cu(II)-phen complexes with human serum albumin (HSA) was also studied at
      pH 7.4 by circular dichroism and EPR spectroscopy, the formation of several HSA
      Cu(II)-phen containing species being confirmed and their binding constants
      determined.

PMID- 22975793
TI  - Public preferences for establishing nephrology facilities in Greenland:
      estimating willingness-to-pay using a discrete choice experiment.
AB  - At present there are no nephrology facilities in Greenland. Greenlandic patients
      with renal failure needing dialysis thus have to travel to Denmark to obtain
      treatment. For patients in haemodialysis this necessitates a permanent residence
      in Denmark. Our study was aimed at examining Greenlanders' preferences for
      establishing nephrology facilities in Greenland at Queen Ingrid's Hospital in
      Nuuk, and to estimate the associated change in welfare. Preferences were elicited
      using a discrete choice experiment (DCE). A random sample of 500 individuals of
      the general population was sent a postal questionnaire in which they were asked
      to consider the trade-offs of establishing nephrology facilities in Greenland as
      opposed to the current situation. This involved trading off the benefits of
      having such facilities in their home country against the costs of the
      intervention. Besides including a payment attribute described in terms of
      incremental tax payment, the DCE included two interventions attributes related to
      (1) the organisation of labour, and (2) the physical settings of the patients.
      Respondents succeeded in answering the DCE despite cultural and linguistic
      disparity. We found that all the included attributes had a significant effect on
      respondents' choices, and that respondents' answers to the DCE were in keeping
      with their values as stated in the questionnaire. DCE data was analyzed using a
      random parameter logit model reparametrized in willingness-to-pay space. The
      results showed that establishing facilities in Greenland were preferred to the
      current treatment in Denmark. The welfare estimate from the DCE, at DKK 18.74
      million, exceeds the estimated annual costs of establishing treatment facilities
      for patients with chronic renal failure. Given the estimated confidence interval
      this result seems robust. Establishing facilities in Greenland therefore would
      appear to be welfare-improving, deriving positive net benefits. Despite the
      relatively narrow policy focus, we believe that our findings provide some insight
      into individuals' preferences for decentralization of public services and on
      citizens' views of 'self-governance' that go beyond the case of Greenland. More
      generally, this paper illustrates how DCE can be applied successfully to
      developing countries with culturally, demographically, and geographically
      distinct features. 

PMID- 22975795
TI  - The comparator model of infant visual habituation and dishabituation: recent
      insights.
AB  - Current knowledge of the perceptual and cognitive abilities in infancy is largely
      based on the visual habituation-dishabituation method. According to the
      comparator model [e.g., Sokolov (1963a) Perception and the conditioned reflex.
      Oxford: Pergamon Press], habituation refers to stimulus encoding and
      dishabituation refers to discriminatory memory performance. The review also
      describes the dual-process theory and the attention disengagement approach. The
      dual-process theory points to the impact of natural stimulus preferences on
      habituation-dishabituation processes. The attention disengagement approach
      emphasizes the contribution of the ability to shift the attention away from a
      stimulus. Moreover, arguments for the cognitive interpretation of visual
      habituation and dishabituations are discussed. These arguments are provided by
      physiological studies and by research on interindividual differences. Overall,
      the review shows that current research supports the comparator model. It
      emphasizes that the investigation of habituation and dishabituation expands our
      understanding of visual attention processes in infants.

PMID- 22975794
TI  - Cost-effectiveness analysis of top-down versus step-up strategies in patients
      with newly diagnosed active luminal Crohn's disease.
AB  - BACKGROUND: Top-down (TD) strategy with frontline infliximab proved to be more
      effective than the traditional step-up (SU) approach in newly diagnosed luminal
      moderate-to-severe CD patients. However, the considerable cost of infliximab
      calls its universal use as frontline treatment into question. The aim of this
      study is to evaluate the cost-effectiveness of the TD approach using a Markov
      decision model. METHODS: Four states were modelled, namely step 1, step 2, step 3
      and death. The first three steps were in TD infliximab induction plus
      azathioprine, infliximab rechallenge plus azathioprine and steroids plus
      azathioprine, and in SU steroid induction, azathioprine plus steroid rechallenge
      and infliximab plus azathioprine. Each health state lasted 1 month. The time
      horizon of the model was 5 years. Transition probabilities and quality of life
      were estimated from a randomised trial. First- and second-order sensitivity
      analyses were done to test the robustness of the results. RESULTS: At baseline
      analysis, TD improved quality-adjusted life expectancy from 3.76 to 3.90 quality
      adjusted life years (QALYs), that is, 0.14 QALYs, while allowing a saving of euro
      773, proving dominant when compared to SU. TD was cost-saving in 66% of the Monte
      Carlo simulations and cost <euro 20,000/QALY in 84%. At sensitivity analysis the
      most significant variables were infliximab cost and time horizon: doubling
      infliximab cost (euro 1,000 per 100 mg vial) resulted in an incremental cost
      utility ratio of euro 12,114/QALY. CONCLUSIONS: TD is a cost-effective treatment
      in newly diagnosed CD patients with luminal moderate-to-severe disease, and
      sensitivity analysis showed the result to be robust.

PMID- 22975796
TI  - Utility of the short double-balloon enteroscope to perform pancreaticobiliary
      interventions in patients with surgically altered anatomy in a US multicenter
      study.
AB  - OBJECTIVE: Double-balloon enteroscopy-assisted endoscopic retrograde
      cholangiopancreaticography (DBE-ERCP) is an effective method for interventions in
      the pancreaticobiliary system in the post-surgical patient. However, use of
      currently available endoscopic accessories during this procedure is limited due
      of the length of the conventional instrument (200 cm). The aim of this study was
      to explore the utility of the short DBE (152 cm) for the management of
      pancreaticobiliary disorders in patients with surgically altered anatomies.
      METHODS: Data were collected retrospectively on patients with various anatomic
      variations in whom ERCP was performed using the short DBE from April 2008 to
      November 2011. Basic demographic information, clinical presentation, preoperative
      imaging, and type of surgery, procedural technical success rate, and adverse
      events were evaluated. Descriptive analysis was used to document the demographic
      and clinical data of the patients. RESULTS: We identified 79 patients in whom DBE
      ERCP was attempted (38 % male, mean age 58 years). Indications for the procedure
      were removal of a previously placed stent (n = 5), suspected sphincter of Oddi
      dysfunction type 1 (n = 3), surgical biliary leak (n = 3), pancreatic anastomotic
      stricture (n = 2), suspected biliary stones (n = 48), and biliary strictures
      visualized on imaging (n = 18). Overall, the success rate of DBE-ERCP in all
      patients was 81 % (64/79). The scope could not reach the papilla or surgical
      anastomosis in 8 cases and duct cannulation failed in 7 cases. The following
      interventions were performed: biliary sphincterotomy (n = 39), dilation of CBD
      stenosis with a balloon (n = 30), biliary stent insertion (n = 25), stone removal
      (n = 35), brushing cytology of biliary strictures (n = 3), and stent retrieval (n
      = 4). Three patients developed post-procedure pancreatitis. There was 1 episode
      of self-limited bleeding. CONCLUSIONS: The current study demonstrates that DBE
      assisted ERCP for pancreaticobiliary interventions using a short enteroscope are
      feasible in patients with surgically altered anatomy.

PMID- 22975797
TI  - Clinical impact of extended-spectrum beta-lactamase-producing Enterobacteriaceae
      in patients with biliary tract infection.
AB  - BACKGROUND: Clinical outcomes associated with Gram-negative bacterial isolates
      with extended spectrum beta-lactamase (ESBL) in patients with biliary tract
      infection are largely unknown. The objective of the present study was to compare
      the demographics, risk factors, and clinical outcomes between patients with
      biliary tract infection caused by ESBL-producing and non-producing Klebsiella
      pneumoniae and Escherichia coli. METHODS: Between February 2005 and August 2010,
      we collected 159 cases with biliary tract infection caused by K. pneumoniae and
      E. coli identified by blood or bile cultures obtained before endoscopic or
      surgical treatment performed at our institution. We also retrospectively
      collected the data of patients' demographic characteristics, co-morbid
      conditions, antimicrobial therapy, and clinical outcomes. RESULTS: Among the 159
      strains isolated, 21 strains (13.2 %) were positive for phenotypical ESBL-test.
      Sepsis was more common in ESBL-positive strains, but did not reach statistical
      significance (23.8 % for ESBL-positive strains and 9.4 % for ESBL-negative
      strains, P = 0.066). Thirty-day mortality was significantly higher in ESBL
      positive strains (3/21, 14.3 %) compared to ESBL-negative strains (4/138, 2.9 %,
      P = 0.049). However, there were no significant differences in overall survival
      between ESBL-positive and ESBL-negative strains. By multivariate analysis,
      inadequate antimicrobial therapy (HR 4.06, 95 % CI 1.08-16.46, P = 0.049) and
      sepsis (HR 6.54, 95 % CI 1.26-33.85, P = 0.025) were independent and significant
      predictors of 30-day mortality. CONCLUSION: ESBL status of bacterial isolates for
      patients with biliary tract infection caused by K. pneumoniae and E. coli has
      clinical impact, especially on the short-term outcomes of those patients.

PMID- 22975799
TI  - Late type III endoleak from fabric tears of a zenith stent graft: report of a
      case.
AB  - We report a case of late type III B endoleak from a fabric tear in the main body
      of a Zenith bifurcated stent-graft approximately 19 months after implantation. A
      follow-up computed tomography (CT) scan showed gradual growth in the size of the
      aneurysm, but no apparent endoleak was recognized. However, the CT scan had
      demonstrated a mosaic pattern in the aneurysm sac, which could indicate an
      endoleak from a fabric tear. The defect was repaired by implantation of body
      extensions, but the patient died 5 h after the procedure.

PMID- 22975798
TI  - Pharmacist-managed chronic obstructive pulmonary disease screening in a community
      setting.
AB  - OBJECTIVES: To implement a spirometry-based chronic obstructive pulmonary disease
      (COPD) screening in a community pharmacy chain, determine whether pharmacists can
      accurately perform spirometry screenings and interpret results, and determine
      whether performing screenings improved enrollment in smoking cessation programs.
      DESIGN: Prospective study. SETTING: Kroger pharmacies in the Cincinnati-Dayton
      Kroger Marketing Area and off-site screening events in Cincinnati, OH, from March
      to December 2010. PATIENTS: Consenting individuals older than 35 years who met
      inclusion and exclusion criteria. INTERVENTION: Specially trained community
      pharmacists administered a validated COPD screening questionnaire and performed
      spirometry. The results were interpreted, given to the patient, and faxed to the
      primary care physician. Any patient who was currently smoking was offered smoking
      cessation counseling. MAIN OUTCOME MEASURES: Spirometry technical quality and
      interpretation accuracy, screening questionnaire scores in relationship to
      spirometry results, number of patients enrolled in smoking cessation programs.
      RESULTS: Of the 185 patients, 10 were excluded due to inability to perform
      spirometry. After review, 174 (99%) of the spirometries were judged acceptable
      and 157 (90%) demonstrated reproducible results. The mean (+/-SD) score on the
      COPD Population Screener questionnaire was 2.3 +/- 1.6 (range 0-8). Airflow
      limitation (defined as forced expiratory volume in 1 second/forced vital capacity
      < lower limit of normal) was detected in 16 (9%) of the patients. Although 12
      (75%) of these patients were former or current smokers, only 3 (19%) were at
      increased risk for COPD based on their screening questionnaire scores. Of the
      nine current smokers who participated in a follow-up interview, two had
      successfully abstained from smoking for 6 months after the screening and five
      others had made an attempt to quit. CONCLUSION: This study demonstrated that
      pharmacists are able to perform accurate and reproducible spirometry in a
      community pharmacy setting.

PMID- 22975800
TI  - Successful management of complex open heart surgery in a patient with Child-Pugh
      class C liver cirrhosis: report of a case.
AB  - Open heart surgery in patients with Child-Pugh class C liver cirrhosis has a high
      mortality rate and is generally considered to be contraindicated. A patient with
      liver cirrhosis (Child-Pugh class C) underwent mandatory complex open heart
      surgery due to severe heart failure. The perioperative management, including the
      prophylactic use of intraaortic balloon pumping to increase the hepatic blood
      flow and the early initiation of continuous veno-venous hemodialysis to avoid
      hepatic congestion, enabled the patient to survive.

PMID- 22975801
TI  - Late recurrence after resection of mass-forming intrahepatic cholangiocarcinoma:
      report of a case.
AB  - The outcome after surgical resection for intrahepatic cholangiocarcinoma has not
      been satisfactorily evaluated due to its malignant behavior. Surgical resection,
      however, has the potential to improve the prognosis and may allow surgeons to
      experience rare cases with long survival. This report presents the case of a
      patient who developed recurrence 9 years after resection of intrahepatic
      cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic
      cholangiocarcinoma and underwent an extended right posterior subsegmentectomy.
      The gross appearance showed a mass-forming type tumor. The histopathological
      examination revealed well to moderately differentiated adenocarcinoma associated
      with portal vein invasion. Subcutaneous metastasis in the head as the first sign
      of relapse was diagnosed 9 years after hepatectomy. The histopathological
      findings of the subcutaneous tumor were similar to those of the intrahepatic
      cholangiocarcinoma, thus suggesting metastasis from intrahepatic
      cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2
      deoxy-D-glucose was useful for detecting multiple metastases. Long-term follow-up
      for more than 5 years is recommended because the present case shows that late
      recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after
      resection.

PMID- 22975802
TI  - Acupuncture improves cognitive deficits and increases neuron density of the
      hippocampus in middle-aged SAMP8 mice.
AB  - OBJECTIVES: To examine whether acupuncture could improve cognitive deficits and
      reduce the loss of neurons in mice models of ageing. METHODS: Male 7.5-month-old
      senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant
      inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8
      acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8
      control group (Pc) and SAMR1 normal control group (Rc). The behaviours were
      examined by the Morris water maze test and the neuron density in the hippocampus
      was estimated by the optical fractionator technique. RESULTS: The Morris water
      maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by
      acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (-24%),
      CA3 (-18%) and DG (-28%) of Pc compared with Rc. The neuron number in hippocampal
      CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture
      compared with the Pc group. CONCLUSIONS: Acupuncture improved the cognitive
      impairment of middle-aged SAMP8 mice which could be attributed to the reduced
      neuron loss in hippocampal regions CA3 and DG. These results suggest that
      reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic
      approach for the treatment of Alzheimer's disease and cognitive impairment
      diseases.

PMID- 22975803
TI  - Spectroscopic analysis of bacterial biological warfare simulants and the effects
      of environmental conditioning on a bacterial spectrum.
AB  - The ability to distinguish bacteria from mixed samples is of great interest,
      especially in the medical and defence arenas. This paper reports a step towards
      the aim of differentiating pathogenic endospores in situ, to aid any required
      response for hazard management using infrared spectroscopy combined with
      multivariate analysis. We describe a proof-of-principle study aimed at
      discriminating biological warfare simulants from common environmental bacteria.
      We also report an evaluation of multiple pre-processing techniques and subsequent
      differences in cross-validation of two pattern recognition models (Support Vector
      Machines and Principal Component-Linear Discriminant Analysis) for a six-class
      classification (bacterial classification). These classifications were possible
      with an average sensitivity of 88.0 and 86.9 %, and an average specificity of
      97.6 and 97.5 % for the SVM and the PC-LDA models, respectively. Most
      spectroscopic models are built upon spectra from bacteria that have been
      specifically prepared for analysis by a particular method; this paper will
      comment upon the differences in the bacterial spectrum that occur between
      specific preparations when the bacteria have spent 30 days in the simulated
      weather conditions of a hot dry climate.

PMID- 22975804
TI  - Fully automated isotopic dimethyl labeling and phosphopeptide enrichment using a
      microfluidic HPLC phosphochip.
AB  - Quantitative detection of phosphorylation levels is challenging and requires an
      expertise in both stable isotope labeling as well as enrichment of phosphorylated
      peptides. Recently, a microfluidic device incorporating a nanoliter flow rate
      reversed phase column as well as a titania (TiO(2)) enrichment column was
      released. This HPLC phosphochip allows excellent recovery and separation of
      phosphorylated peptides in a robust and reproducible manner with little user
      intervention. In this work, we have extended the abilities of this chip by
      defining the conditions required for on-chip stable isotope dimethyl labeling
      allowing for automated quantitation. The resulting approach will make
      quantitative phosphoproteomics more accessible.

PMID- 22975805
TI  - The transcriptional landscape and mutational profile of lung adenocarcinoma.
AB  - All cancers harbor molecular alterations in their genomes. The transcriptional
      consequences of these somatic mutations have not yet been comprehensively
      explored in lung cancer. Here we present the first large scale RNA sequencing
      study of lung adenocarcinoma, demonstrating its power to identify somatic point
      mutations as well as transcriptional variants such as gene fusions, alternative
      splicing events, and expression outliers. Our results reveal the genetic basis of
      200 lung adenocarcinomas in Koreans including deep characterization of 87
      surgical specimens by transcriptome sequencing. We identified driver somatic
      mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and
      CTNNB1. Candidates for novel driver mutations were also identified in genes newly
      implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We
      found 45 fusion genes, eight of which were chimeric tyrosine kinases involving
      ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing
      events, we identified exon 14 skipping in the proto-oncogene MET as highly likely
      to be a cancer driver. The number of somatic mutations and expression outliers
      varied markedly between individual cancers and was strongly correlated with
      smoking history of patients. We identified genomic blocks within which gene
      expression levels were consistently increased or decreased that could be
      explained by copy number alterations in samples. We also found an association
      between lymph node metastasis and somatic mutations in TP53. These findings
      broaden our understanding of lung adenocarcinoma and may also lead to new
      diagnostic and therapeutic approaches.

PMID- 22975806
TI  - Metal ions guided self-assembly of therapeutic proteins for controllable release:
      from random to ordered aggregation.
AB  - PURPOSE: To make a comparative study on sustained delivery performance of rhIFN
      with random amorphous and spherical crystal-like ordered self-assemblies.
      METHODS: The rhIFN self-assemblies were identified in batch crystallization mode.
      Physico-chemical characteristics were compared, including morphology, XRD, FTIR,
      CD, biological potency, the dissolution behaviors in vitro and plasma
      pharmacokinetics in vivo. Moreover, molecular simulation was performed to better
      understand their binding site and mode. RESULTS: Here, we suggest that random
      amorphous and spherical ordered self-assemblies allow for long action without new
      molecular entities generation or carriers employed. By manipulating
      supersaturation, the ordered aggregates were self-organized at high concentration
      of Zn(II) (>100 mM) in pH 5.5-6.0, which was the first time that spherical semi
      crystals of rhIFN can act as a depot source for the sustained delivery of
      biologically active proteins. The secondary structure and biological potency of
      rhIFN were unchanged after aggregation. Compared with that of the native rhIFN,
      both self-assemblies exhibited slower absorption and extended elimination
      profiles after s.c. administration, which were characterized as 4.75 +/- 0.82 h
      and 10.58 +/- 1.86 h of terminal half-life for random amorphous and spherical
      ordered self-assemblies, respectively. CONCLUSIONS: The work described here
      demonstrates the possibility of self-assemblies of biomacromolecules for
      controllable release application of therapeutic proteins.

PMID- 22975807
TI  - Evaluation of poly (1, 6-bis-(p-carboxyphenoxy) hexane-co-sebacic acid
      microspheres for controlled basal insulin delivery.
AB  - PURPOSE: To develop poly 1,3-bis-(p-carboxyphenoxy) hexane-co-sebacic acid
      (p(CPH/SA)) microspheres for controlled basal insulin delivery and evaluate their
      in vivo efficacy and toxicity. METHODS: A series of CPH/SA copolymers with molar
      ratios 20/80, 40/60, and 50/50 were synthesized and characterized. The stability
      of encapsulated insulin and the fraction of insulin released from microspheres
      were assessed by different analytical techniques. The skin from the injection
      site of rats was examined microscopically for histomorphological changes.
      RESULTS: Increasing the molar ratio of CPH/SA significantly (p < 0.05) improved
      insulin loading and controlled insulin release. However, dimer aggregates of
      insulin were observed as CPH/SA molar ratio increased. Co-encapsulation of zinc
      oxide with insulin inhibited dimer aggregate formation and further controlled
      insulin release. Insulin was stable after entrapment into microspheres and during
      in vitro release studies. Administration of microsphere formulations CPH/SA 40/60
      and 50/50 with zinc oxide controlled insulin release and maintained basal insulin
      levels for 42 days in rats. Skin sections showed minimal inflammation with no
      evidence for histomorphological changes and toxicity. CONCLUSIONS: Insulin-loaded
      CPH/SA microspheres demonstrated considerable potential as controlled delivery
      system for insulin. Copolymer microspheres maintained basal insulin levels for 42
      days and were biodegradable and biocompatible.

PMID- 22975808
TI  - Prevalence of low back symptoms and its consequences in relation to occupational
      group.
AB  - BACKGROUND: The purpose of this study was to examine: (1) the prevalence of low
      back symptoms (LBS) and its consequences (reduced activities and absenteeism);
      (2) the association between occupational group and LBS; and (3) the association
      between LBS and its consequences. METHODS: A self-administered questionnaire was
      used to determine the prevalence of LBS in 1,294 Indonesian coal mining workers.
      A Cox proportional hazards model was developed to quantify the 12-monthly hazard
      of LBS. Logistic regression models were developed to identify risk factors for
      reduced activity and absenteeism from the workplace. RESULTS: The 12-month period
      prevalence for LBS, reduced activities, and absenteeism were 75%, 16%, and 13%,
      respectively. The 12-monthly hazard of LBS for blue-collar workers was 1.85 (95%
      CI: 1.06-3.25) times that of white-collar workers. LBS and smoking increased the
      risk of reduced activity and absenteeism. CONCLUSIONS: Indonesian coal mining
      workers have a high prevalence of LBS. The findings imply that efforts to reduce
      LBS and in the workplace should focus on blue-collar workers. For smokers who
      report reduced activities and/or absenteeism, there should be a focus on
      rehabilitation and/or return-to-work programs.

PMID- 22975809
TI  - School physical activity policy assessment.
AB  - BACKGROUND: Physical activity (PA) levels in schools vary widely, and there is
      interest in studying how student PA accrual relates to school policy and
      environmental conditions. School PA policy research, however, is in its infancy
      and generalizable measurement tools do not exist. We developed and assessed
      reliability of items on the School Physical Activity Policy Assessment (S-PAPA),
      an instrument designed to assess school PA policy related to physical education
      (PE), recess, and other opportunities. METHODS: To develop items, we perused
      associated literature, examined existing instruments, and consulted school policy
      makers. For test-retest reliability assessment, 31 elementary school PE teachers
      completed the survey twice, 14 days apart. RESULTS: S-PAPA uses open-ended,
      dichotomous, multichotomous, and checklist formatting and has 3 modules: 1)
      Physical Education (47 items), 2) Recess (27 items), and 3) Other Before, During,
      and After School Programs (15 items). Responses to more than 95% of items were
      highly related between Times 1 and 2. Generally, physical education and recess
      items had fair to substantial levels of agreement, and items about other school
      PA programs had fair to perfect agreement. CONCLUSIONS: Test-retest results
      suggest S-PAPA items are reliable and useful in assessing PA policies in
      elementary schools.

PMID- 22975810
TI  - X-ray lasers for structural and dynamic biology.
AB  - Research opportunities and techniques are reviewed for the application of hard x
      ray pulsed free-electron lasers (XFEL) to structural biology. These include the
      imaging of protein nanocrystals, single particles such as viruses, pump--probe
      experiments for time-resolved nanocrystallography, and snapshot wide-angle x-ray
      scattering (WAXS) from molecules in solution. The use of femtosecond exposure
      times, rather than freezing of samples, as a means of minimizing radiation damage
      is shown to open up new opportunities for the molecular imaging of biochemical
      reactions at room temperature in solution. This is possible using a 'diffract-and
      destroy' mode in which the incident pulse terminates before radiation damage
      begins. Methods for delivering hundreds of hydrated bioparticles per second (in
      random orientations) to a pulsed x-ray beam are described. New data analysis
      approaches are outlined for the correlated fluctuations in fast WAXS, for protein
      nanocrystals just a few molecules on a side, and for the continuous x-ray
      scattering from a single virus. Methods for determining the orientation of a
      molecule from its diffraction pattern are reviewed. Methods for the preparation
      of protein nanocrystals are also reviewed. New opportunities for solving the
      phase problem for XFEL data are outlined. A summary of the latest results is
      given, which now extend to atomic resolution for nanocrystals. Possibilities for
      time-resolved chemistry using fast WAXS (solution scattering) from mixtures is
      reviewed, toward the general goal of making molecular movies of biochemical
      processes.

PMID- 22975811
TI  - [Molecular mechanism and treatment of juvenile myelomonocytic leukemia (JMML)].

PMID- 22975812
TI  - [Molecular mechanisms underlying leukemic transformation of myelodysplastic
      syndromes (MDS) and chronic myelogenous leukemia (CML)].

PMID- 22975813
TI  - [Biological features and therapeutic strategies of acute lymphoblastic leukemia
      in adolescents and young adults].

PMID- 22975814
TI  - [Feasibility and safety of chemotherapy for acute lymphoblastic leukemia in
      adolescents and young adults: Interim analysis of JALSG ALL202-U].

PMID- 22975815
TI  - [Immunophenotypic analysis of hematogones in patients with hematological
      malignancies].
AB  - We studied immunophenotypic analysis of hematogones by flow cytometry. A total of
      102 specimens from 93 patients with acute leukemia (52 specimens),
      myelodysplastic syndromes (4), or malignant lymphoma (46) were analyzed between
      April and August, 2011. Hematogones were detected in 55 specimens and highly
      identified in patients with acute myeloid leukemia in remission and B cell
      lymphoma. Stage 1 (CD34(+)CD20(-)) and stage 2/3 (CD34(-)CD20(+)) were detected
      in 9.9% and 52.7%, respectively. In addition, the intermediate type
      (CD34(+)CD20(+)) was identified in 37.4%. All specimens of stage 3 in bright CD45
      expression were positive for CD5 and included CD5(+)CD23(-)CD11c(-), 11.1%,
      CD5(+)CD23(+)CD11c(-), 85.2%, and CD5(+)CD23(+)CD11c(+), 3.7%. These findings
      suggest that hematogones with unreported immunophenotypes may exist and the
      appearance of hematogones in hematologic malignancies may be relatively frequent.

PMID- 22975816
TI  - [Early onset of paralytic ileus caused by simultaneous administration of
      bortezomib and azole antifungals in multiple myeloma patients].
AB  - We herein report two patients (70- and 45-year-old men) with refractory multiple
      myeloma who developed paralytic ileus shortly after starting bortezomib therapy.
      Bortezomib (1.3 mg/m(2)) was given on days 1, 4, 8, and 11 with daily oral
      solution itraconazole or voriconazole. Twelve and 15 days after beginning the
      therapy, each patient developed paralytic ileus. Interestingly, no other signs of
      peripheral neuropathy such as fingertip numbness were observed at the onset of
      ileus. Sporadic cases of paralytic ileus after bortezomib therapy have been
      reported, most of which developed ileus after several courses of bortezomib
      therapy. Our cases developed paralytic ileus shortly after initiating bortezomib,
      strongly suggesting that autonomic neuropathy due to bortezomib was induced by
      the concomitant use of itraconazole or voriconazole.

PMID- 22975817
TI  - [Diagnosis of mild hemophilia A made by massive intraabdominal bleeding in a 13
      year-old boy].
AB  - We report a 13-year-old boy who had massive intra-abdominal bleeding without a
      history of bleeding episodes or traumatic cause of bleeding. The patient
      underwent surgical treatment because bleeding was not controlled after treatment
      with tranexamic acid and transfusions including fresh-frozen plasma. Bleeding was
      traced to the lower left lobe of the liver. The mother's side of the family had a
      history of bleeding episodes in the boy's grandfather, great uncle, and son of a
      great aunt. A low level of plasma factor VIII coagulant activity (22%) led to a
      diagnosis of mild hemophilia A. Compared with severe hemophilia, mild hemophilia
      is more difficult to diagnose because bleeding episodes are less frequent. Most
      cases are found after incidental trauma or uncontrolled surgery-related bleeding,
      there is rarely a family history of hemophilia and activated partial
      thromboplastin time is normal or slightly prolonged. However, bleeding episodes
      in mild hemophilia may result in excessive, sometimes life-threatening hemorrhage
      and require early diagnosis and replacement treatment with adequate amounts of
      factor VIII, as in severe hemophilia.

PMID- 22975818
TI  - [Successful delivery following treatment with plasma exchange in a female patient
      with thrombotic thrombocytopenic purpura].
AB  - We report here on a case of a 27-year-old woman in her first pregnancy. She was
      diagnosed with idiopathic thrombocytopenic purpura (ITP) at the age of 14 years.
      At 36 weeks of gestation, she was admitted to our hospital due to
      thrombocytopenia. We initially suspected ITP exacerbated by pregnancy. Laboratory
      results revealed mild anemia, thrombocytopenia (5.0*10(9)/l), and slightly
      elevated liver enzymes and lactate dehydrogenase. The next day, hemoglobin fell
      to 6.6 g/dl. Thrombotic thrombocytopenic purpura (TTP) was suspected on the basis
      of hemolytic anemia with schistocytes and a negative Coombs' test. Plasma
      exchange and methylprednisolone were initiated immediately. ADAMTS13 analysis
      showed a severe deficiency in ADAMTS13 activity but no inhibitors. At Day 6, the
      platelet count rose to 223*10(9)/l and she delivered a live baby by cesarean
      section. Currently, the patient receives fresh frozen plasma infusions every 2
      weeks due to suspected Upshaw-Schulman syndrome.

PMID- 22975819
TI  - [Fatal disseminated toxoplasmosis after unrelated bone marrow transplantation for
      myelodysplastic syndrome].
AB  - A 44-year-old man with myelodysplastic syndrome (RAEB-2) underwent allogeneic
      bone marrow transplantation from an unrelated donor after being conditioned with
      myeloablative regimen. Tacrolimus and short-term methotrexate were given for
      prophylaxis against graft-versus-host disease (GVHD). Engraftment was achieved on
      Day 17. He developed Grade II acute GVHD involving the skin and gastrointestinal
      tract and methylprednisolone (2 mg/kg) was initiated. On Day 60, he developed
      fever and liver dysfunction followed by diffuse interstitial infiltration of the
      lungs. Respiratory and cardiac failure rapidly progressed and the patient died on
      Day 66 despite treatment with antimicrobial agents and intravenous
      immunoglobulin. Autopsy findings revealed disseminated toxoplasmosis involving
      the lungs, heart, liver, gastrointestinal tract, and kidneys. Toxoplasmosis after
      allogeneic hematopoietic stem cell transplantation (HSCT) generally manifests as
      encephalopathy or brain abscess; however, disseminated disease has been
      sporadically reported. It should be recognized as a possible cause of rapidly
      progressing interstitial pneumonitis and cardiac dysfunction after allogeneic
      HSCT.

PMID- 22975820
TI  - [Alleviation of palmoplantar pustulosis associated with adult T cell
      leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation].
AB  - A 68-year-old female with palmoplantar pustulosis was referred to our hospital in
      July, 2009 because of liver dysfunction, a positive test for HTLV-1, and
      circulating abnormal lymphocytes with irregularly shaped nuclei. A diagnosis of
      acute type adult T cell leukemia/lymphoma (ATLL) was made based on generalized
      lymph node swelling and high levels of serum LDH, in addition to the findings
      described above. The associated palmoplantar pustulosis responded to some extent
      to antibiotics, steroid ointment, and narrow band UBV light irradiation. For
      ATLL, she was serially treated with CHOP chemotherapy, an LSG 15 protocol, and
      CytaBOM protocol with consequent partial remission. These chemotherapies did not
      affect the palmoplantar pustulosis. For ATLL in partial remission, we performed
      allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from a related
      donor (HTLV-1-negative) with a conditioning regimen consisting of fludarabine,
      melphalan, and total body irradiation with 3 Gy in February, 2010. After the
      engraftment of donor hematopoietic cells, ATLL cells disappeared and the patient
      currently (as of April, 2012) remains in complete remission (CR). The residual
      palmoplantar pustulosis was further improved soon after allo-PBSCT and
      disappeared on Day 84 after transplantation. This refractory skin disease has
      also been in CR to date.

PMID- 22975821
TI  - [Diminished expression of CD5 and/or CD7 surface antigens as the first clue of
      diagnosis for monoclonal T lymphocytosis].
AB  - The significance of precursor status for mature T-cell neoplasms has not been
      elucidated. Diagnosis of T-cell neoplasms is often challenging and sometimes
      overlooked when leukocytosis is not evident and neoplastic cell morphology is
      hardly distinguishable. Here, we report two cases of monoclonal T lymphocytosis
      (MTL) without evident lymphocytosis and lymphadenopathies that show slightly
      diminished CD5 and/or CD7 surface antigens as the first clue of diagnosis.
      Recently, some reports have demonstrated the possibility that monoclonal
      lymphocytosis precedes leukemia/lymphoma. Although its clinical significance is
      unknown, flow cytometric analysis of peripheral blood is useful for detection of
      occult MTL and careful follow-up is required.

PMID- 22975822
TI  - [Innovation of animal models for cognitive impairment in schizophrenia (CIS)].

PMID- 22975823
TI  - [Role of neuroimaging biomarker in drug discovery for schizophrenia].

PMID- 22975824
TI  - [Discovery of novel antipsychotics targeting group II metabotropic glutamate
      receptor].

PMID- 22975825
TI  - [Approach for identifying novel drug targets of schizophrenia].

PMID- 22975826
TI  - [Role of the renin-angiotensin system in the brain and cardiorenal system].

PMID- 22975827
TI  - [GVP (Good Vigilance Practice) regulation].

PMID- 22975828
TI  - [Molecular targeted anticancer agents in the First in Human study--possibility
      for dosing healthy volunteers].

PMID- 22975829
TI  - [Drug information and JAPIC (Japan Pharmaceutical Information Center)].

PMID- 22975830
TI  - Emergency neurological life support: traumatic brain injury.
AB  - Traumatic brain injury (TBI) was chosen as an Emergency Neurological Life Support
      topic due to its frequency, the impact of early intervention on outcomes for
      patients with TBI, and the need for an organized approach to the care of such
      patients within the emergency setting. This protocol was designed to enumerate
      the practice steps that should be considered within the first critical hour of
      neurological injury.

PMID- 22975831
TI  - Benign myelitis as a first presentation of systemic sarcoidosis: importance of
      early diagnosis and treatment.

PMID- 22975832
TI  - Correlation between motor performance scales, body composition, and anthropometry
      in patients with Duchenne muscular dystrophy.
AB  - The aim of this study is to investigate the relationship between body
      composition, anthropometry, and motor scales in patients with Duchenne muscular
      dystrophy (DMD). Twenty six patients with DMD were evaluated by Expanded
      Hammersmith Functional Motor Scale (HFMSE), gross motor function classification
      system (GMFCS), multifrequency bioelectrical impedance analysis, and
      anthropometric measurements. Seventeen healthy children served as control group.
      There were 26 patients with a mean age of 9.5 +/- 4.8 years. Ages and
      anthropometric measurements did not differ between groups. Of the 26 patients,
      nine were level I, seven were level II, two were level III, seven were level IV,
      and one was level V, according to the GMFCS. Despite the similar percentage of
      total body water, extracellular water/intracellular water ratio was significantly
      elevated in DMD patients (p = 0.001). Increased values of fat percentage and body
      fat mass index (BFMI) correlated positively with elevated GMFCS levels (r = 0.785
      and 0.719 respectively). Increased fat-free mass index (FFMI) correlated
      negatively with elevated GMFCS levels (r = -0.401). Increased fat percentage and
      BFMI correlated negatively with HFMSE scores (r = -0.779 and -0.698,
      respectively). Increased values of FFMI correlated positively with HFMSE scores.
      There was also a negative correlation between increased skin fold measurements
      from triceps and scapula and HFMSE scores (r = -0.618 and -0.683, respectively).
      Increased skin fold values from the same regions correlated positively with
      elevated GMFCS levels (r = 0.643 and 0.712, respectively). Significant body
      composition changes occur in patients with DMD. Anthropometric and multifrequency
      bioelectrical impedance analyses measurements show good correlation between motor
      function scales. These results may also be helpful to evaluate the effects of new
      treatment strategies.

PMID- 22975833
TI  - Occipital neuralgia as an unusual manifestation of herpes zoster infection of the
      lesser occipital nerve: a case report.

PMID- 22975834
TI  - The thing of which she could not speak: transient biopercular syndrome as a very
      late complication of unsuccessful chemical abortion.

PMID- 22975835
TI  - Long-term follow-up results of multimodal treatment with initial surgical
      approach for acromegaly in a single center.
AB  - The purpose of this study is to evaluate long-term results in acromegaly patients
      who received surgery as first-line treatment. Repeated surgery, radiation therapy
      and medical treatment were considered in patients showing no postoperative
      remission or who suffered a relapse. Thirty-five patients suffering from
      acromegaly were operated on between 1993 and 2009. The patients with persistent
      hypersecretion received a new surgery when postoperative imaging showed localized
      residual lesion. The other cases with persistent hypersecretion were treated
      medically using dopamine agonists, somatostatin analogs or pegvisomant according
      to the efficiency obtained. Radiotherapy was considered when medical treatment
      failed to normalize hormonal hypersecretion. The overall remission rate with
      surgery alone was 57 % (20/35):84 % (16/19) with non-invasive adenomas and 25 %
      (4/16) with invasive adenomas. Fifteen patients showing no remission after
      surgery received additional medical and/or radiation therapy resulting in
      hormonal control in ten of them. Recurrences after initial postoperative
      remission were observed in six patients who were controlled with subsequent
      therapy. Using a multimodal treatment approach, the disease was brought under
      control in 86 % (30/35) of acromegaly patients. Surgery alone produced
      satisfactory initial results in non-invasive adenomas, but additional treatments
      were required for most of the invasive lesions.

PMID- 22975836
TI  - Striatal infarct with paroxysmal nonkinesigenic dyskinesia.

PMID- 22975837
TI  - Ambivalence among neurologists and neurosurgeons on the treatment of chronic
      subdural hematoma: a national survey.
AB  - No class I evidence exists about the optimal treatment of chronic subdural
      hematoma (CSDH). The aim of this study was to evaluate current practice of CSDH
      patients with different neurological grades, and probable ambivalence towards
      various treatment paradigms, especially primary treatment with high-dose
      corticosteroids, among vascular neurologists and neurosurgeons. A questionnaire
      survey containing 4 questions, 1 consisting of cases, was sent to every vascular
      neurologist (n = 83) and neurosurgical centre (n = 15) in the Netherlands. The
      various treatment options were related to the treating physician, geographical
      distribution, both in general and for individual case. Sixty-two percent of
      surveys were returned. The proportion of patients primarily treated with
      corticosteroids was 17.5 % in 2009 and 20.5 % in 2010. Surgery by either burr
      holes or craniotomy was favoured by 61.1 % as primary treatment, and conservative
      treatment with corticosteroids by 22.4 %. Case studies revealed that surgery was
      preferred in case of severe neurological symptoms, whereas wait-and-see policy
      was preferred in case of mild symptoms without midline shift, of which 28 % would
      administer corticosteroids. Variety in answers was obtained in less pronounced
      cases. In the Netherlands, neurologists and neurosurgeons appear to favour
      surgery in CSDH patients as primary treatment, especially in severe cases. An
      ambivalent approach towards treatment protocols was shown, especially in patients
      with mild symptoms, regardless of hematoma size. A regimen of high-dose
      corticosteroids only, is preferred by about a quarter and predominantly in milder
      cases, and might depend on geographical distribution. These results suggest the
      need for a well-designed randomized trial.

PMID- 22975838
TI  - Diffusion-weighted imaging of intramural hematoma in internal carotid artery
      dissection.

PMID- 22975839
TI  - A multiscale approach in the computational modeling of the biophysical
      environment in artificial cartilage tissue regeneration.
AB  - Tissue Engineering is a strongly interdisciplinary scientific area aimed at
      understanding the principles of tissue growth to produce biologically functional
      replacements for clinical use. To achieve such an ambitious goal, complex
      biophysical phenomena must be understood in order to provide the appropriate
      environment to cells (nutrient delivery, fluid-mechanical loading and structural
      support) in the bioengineered device. Such a problem has an inherent
      multiphysics/multiscale nature, as it is characterized by material
      heterogeneities and interplaying processes occurring within a wide range of
      temporal and spatial scales. In this context, computational models are useful to
      gain a quantitative and comprehensive understanding of phenomena often difficult
      to be accessed experimentally. In this paper, we propose a mathematical and
      computational model that represents, to our knowledge, the first example of a
      self-consistent multiscale description of coupled nutrient mass transport, fluid
      dynamics and biomass production in bioengineered constructs. We specifically
      focus on articular cartilage regeneration based on dynamically perfused
      bioreactors, and we investigate by numerical simulations three issues critical in
      this application. First, we study oxygen distribution in the construct, since
      achieving an optimal level throughout the construct is a main control variable to
      improve tissue quality. Second, we provide a quantitative evaluation of how
      interstitial perfusion can enhance nutrient delivery and, ultimately, biomass
      production, compared with static culture. Third, we perform a sensitivity
      analysis with respect to biophysical parameters related to matrix production,
      assessing their role in tissue regeneration. 

PMID- 22975840
TI  - Pharmacist education in the era of genomic medicine.
AB  - Pharmacists are increasingly expected to incorporate an understanding of the
      genomic contributions to medication management in their daily practice,and a
      general consensus exists that many pharmacists are not adequately prepared to
      effectively make use of genomic information. In November 2011, the National Human
      Genome Research Institute of the National Institutes of Health convened a meeting
      to discuss the status of genomics education for pharmacists. A variety of
      pharmacist organizations and other stakeholder groups attended the 2-day event
      and explored the current status of pharmacist genomic education, barriers and
      facilitators to enhanced education, and important next steps to ensure that
      pharmacists are prepared for the coming decades. This report summarizes the
      background, content,and outcomes from this meeting.

PMID- 22975841
TI  - Impact of chronic kidney disease on a re-percutaneous coronary intervention for
      sirolimus-eluting stent restenosis.
AB  - OBJECTIVES: Recurrent in-stent restenosis remains an important clinical issue
      after a percutaneous coronary intervention even after treatment with a sirolimus
      eluting stent (SES) especially in patients with chronic kidney disease. We
      evaluated the impact of renal insufficiency on the clinical and angiographic
      outcomes after treatment for SES restenosis. METHODS AND RESULTS: A total of 74
      patients with 76 lesions underwent subsequent revascularization with a drug
      eluting stent for SES restenosis. Patients were classified into three groups:
      group 1 included 29 patients with an estimated glomerular filtration rate more
      than 60 ml/min/1.73 m(2); group 2 included 27 patients with lower estimated
      glomerular filtration rate (<60 ml/min/1.73 m(2)) without hemodialysis (HD)
      dependence; and group 3 included 18 patients on HD. Clinical and angiographic
      follow-up was carried out at 8 months. Late lumen loss at the 8-month follow-up
      angiography showed progressive increases from group 1 to 2 to 3 (group 1: 0.36 +/
      0.39 mm, group 2: 1.11 +/- 0.61 mm, group 3: 1.30 +/- 0.85 mm, P<0.001).
      Similarly, compared with group 1, groups 2 and 3 had significantly higher rates
      of major adverse cardiac events (6.9, 37.0, and 38.9%, respectively, P=0.001),
      primarily because of a high frequency of target lesion revascularization (8.0,
      34.8, and 33.3%, respectively, P=0.019). CONCLUSION: Non-HD-dependent chronic
      kidney disease patients had increased neointimal growth in the follow-up phase
      after percutaneous coronary intervention, with a drug-eluting stent for SES
      restenosis almost equivalent to patients on HD, resulting in higher rates of
      recurrent restenosis than patients with preserved renal function.

PMID- 22975842
TI  - Effects of mutating aromatic surface residues of the heme domain of human sulfite
      oxidase on its heme midpoint potential, intramolecular electron transfer, and
      steady-state kinetics.
AB  - Human sulfite oxidase (hSO), an essential molybdoheme enzyme, catalyzes the
      oxidation of toxic sulfite to sulfate. The proposed catalytic cycle includes two,
      one-electron intramolecular electron transfers (IET) between the molybdenum (Mo)
      and the heme domains. Rapid IET rates are ascribed to conformational changes that
      bring the two domains into close proximity to one another. Previous studies of
      hSO have focused on the roles of conserved residues near the Mo active site and
      on the tether that links the two domains. Here four aromatic surface residues on
      the heme domain (phenylalanine 57 (F57), phenylalanine 79 (F79), tyrosine 83
      (Y83), and histidine 90 (H90)) have been mutated, and their involvement in IET
      rates, the heme midpoint potential, and the catalytic activity of hSO have been
      investigated using laser flash photolysis, spectroelectrochemistry, and steady
      state kinetics, respectively. The results indicate that the size and
      hydrophobicity of F57 play an important role in modulating the heme potential and
      that F57 also affects the IET rates. The data also suggest that important
      interactions of H90 with a heme propionate group destabilize the Fe(III) state of
      the heme. The positive charge on H90 at pH <= 7.0 may decrease the electrostatic
      interaction between the Mo and heme domains, thereby decreasing the IET rates of
      wt hSO at low pH. Lastly, mutations of F79 and Y83, which are located on the
      surface of the heme domain, but not in direct contact with the heme or the
      propionate groups, have little effect on either IET or the heme potential.

PMID- 22975843
TI  - Patterns of paediatric analgesic use in Africa: a systematic review.
AB  - We conducted a systematic literature review with two objectives: (1) to assess
      reported patterns of analgesic use in African children and compare these observed
      patterns to the analgesics given in the WHO Essential Medicines List for Children
      (EMLc); and (2) to summarise outcomes related to effectiveness, adverse events,
      cost and accessibility of these analgesics. Eligible participants were children
      (<=12 years) living in any African country who received an analgesic administered
      with the intention of relieving pain in any setting. Thirty-four peer-reviewed,
      observational studies representing 7772 African children were accepted. Studies
      were conducted in 25 different regions of 12 countries. Pain was attributed to
      surgery, burns, sickle cell anaemia and conditions requiring palliation in 32% of
      children, and was unspecified in the other 68%. Of the three EMLc analgesics,
      paracetamol and ibuprofen were widely employed, constituting ~60% of all
      analgesics, while morphine was used in 20 children (0.2%). There were 455
      suspected adverse drug reactions which included 17 deaths. Analgesic use reported
      in African children appears to fall short of WHO standards.

PMID- 22975844
TI  - Downregulation of MSP58 suppresses cell proliferation in neuroblastoma cell
      lines.
AB  - MSP58, a novel oncogene, shows transforming activity in mouse embryonic
      fibroblasts. However, the oncogenic role of MSP58 in tumor cells has not been
      fully characterized. To extend understanding of how this protein operates in
      tumorigenesis, we aimed to identify the effect of MSP58 on neuroblastoma cell
      proliferation. Here, we found that MSP58 was highly expressed in neuroblastoma
      tumor samples and cell lines. We found that the majority of MSP58 protein can be
      detected in the nucleus as reported in other cells. Moreover, MSP58-targeted
      shRNA lentivirus attenuated neuroblastoma cell proliferation. Knockdown of MSP58
      resulted in S-phase cell accumulation, which was accompanied by changes in cell
      cycle-related molecules. These results indicate that MSP58 plays an oncogenic
      role in the proliferation of neuroblastoma cells and could be a novel target for
      the treatment of neuroblastoma.

PMID- 22975845
TI  - Functional roles of endogenous D-serine in pain-induced ultrasonic vocalization.
AB  - The N-methyl-D-aspartate receptor (NMDAR) is crucial for pain-related behaviors.
      D-Serine is synthesized from L-serine by serine racemase (SR) and modulates NMDAR
      functions by acting as an agonist at the glycine-binding site. We analyzed
      noxious stimulus-induced ultrasonic vocalization and locomotor activity in the
      open-field test using SR knockout (SR-KO) mice to examine the role of endogenous
      D-serine in mammalian behaviors. SR-KO mice emitted less ultrasonic vocalization
      after noxious stimulation (VAS) than wild-type (WT) mice. The locomotor activity
      of WT mice decreased with repeated daily exposures to the open field, whereas
      that of SR-KO mice remained unchanged. VAS was significantly enhanced during
      arthritis in WT mice, whereas it was not enhanced during arthritis in SR-KO mice.
      These results indicate that mice lacking the ability to produce D-serine
      endogenously in the brain differ from normal mice with respect to the chronic
      pain-induced behavioral changes.

PMID- 22975846
TI  - Amphiphysin-1 protein level changes associated with tau-mediated
      neurodegeneration.
AB  - Tauopathies are a family of neurodegenerative diseases that have the pathological
      hallmark of intraneuronal accumulation of filaments composed of
      hyperphosphorylated tau proteins that tend to aggregate in an ultrastructure
      known as neurofibrillary tangles. The identification of mutations on the tau gene
      in familial cases of tauopathies underscores the pathological role of the tau
      protein. However, the molecular process that underlines tau-mediated
      neurodegeneration is not understood. Here, a proteomics approach was used to
      identify proteins that may be affected during the course of tau-mediated
      neurodegeneration in the tauopathy mouse model JNPL3. The JNPL3 mice express
      human tau proteins bearing a P301L mutation, which mimics the neurodegenerative
      process observed in humans with tauopathy. The results showed that the protein
      amphiphysin-1 (AMPH1) is significantly reduced in terminally ill JNPL3 mice.
      Specifically, the AMPH1 protein level is reduced in brain regions known to
      accumulate aggregates of hyperphosphorylated tau proteins. The AMPH1 protein
      reduction was validated in Alzheimer's disease cases. Taken together, the results
      suggest that the reduction of the AMPH1 protein level is a molecular event
      associated with the progression of tau-mediated neurodegeneration.

PMID- 22975847
TI  - Effects of experimentally induced hyperthyroidism on central hypothalamic
      pituitary-adrenal axis function in rats: in vitro and in situ studies.
AB  - Hyperthyroidism is associated with hypercorticosteronemia, although the locus
      that is principally responsible for the hypercorticosteronism remains unclear.
      The purpose of this study was to assess the effects of hyperthyroidism on the
      functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to
      identify the locus in the HPA axis that is principally affected, and address the
      time-dependent effects of alterations in thyroid status. The functional integrity
      of each component of the HPA axis was examined in vitro and in situ in sham
      thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized
      rats given pharmacological dose (50 MUg) of thyroxin for 7 or 60 days. Basal
      plasma corticosterone and corticosterone binding globulin (CBG) concentrations
      were significantly increased in short- and long-term hyperthyroid rats, and by 60
      days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH
      content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH
      release from hypothalamic culture were increased in long-term hyperthyroid rats.
      There was a significant increase in the content of both ACTH and beta-endorphin
      in the anterior pituitaries of both short- and long-term hyperthyroid animals.
      Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA
      expression in the anterior pituitary, and chronically hyperthyroid animals showed
      increased stress-induced POMC mRNA expression. Adrenal cultures taken from short
      term hyperthyroid rats responded to exogenous ACTH with an exaggerated
      corticosterone response, while those taken from 60-day hyperthyroid animals
      showed responses similar to controls. The findings show that hyperthyroidism is
      associated with hypercorticosteronemia and HPA axis dysfunction that becomes more
      pronounced as the duration of hyperthyroidism increases. The evidence suggests
      that experimentally induced hyperthyroidism is associated with central
      hyperactivity of the HPA axis.

PMID- 22975848
TI  - [Neuroimmune connections in inflammation and pain. ImmunoPain].

PMID- 22975849
TI  - alpha-Lipoic acid interaction with dopamine D2 receptor-dependent activation of
      the Akt/GSK-3beta signaling pathway induced by antipsychotics: potential
      relevance for the treatment of schizophrenia.
AB  - Chronic administration of antipsychotics has been associated with dopamine D2
      receptor (D2R) upregulation and tardive dyskinesia. We have previously shown that
      haloperidol, a first-generation antipsychotic (FGA), exerted an increase in D2R
      expression and oxidative stress and that (+/-)-alpha-lipoic acid reversed its
      effect. Previous studies have implicated the Akt/glycogen synthase kinase-3beta
      (GSK-3beta) signaling pathway in antipsychotic action. These findings led us to
      examine whether the Akt/GSK-3beta pathway was involved in D2R upregulation and
      oxidative stress elicited by antipsychotics and, in (+/-)-alpha-lipoic acid
      induced reversal of these phenomena, in SH-SY5Y cells. Antipsychotics increased
      phosphorylation of Akt and GSK-3beta, and additive effects were observed with (+/
      )-alpha-lipoic acid. GSK-3beta inhibitors reversed haloperidol-induced
      overexpression of D2R mRNA levels but did not affect haloperidol-induced
      oxidative stress. Sustained antipsychotic treatment increased beta-arrestin-2 and
      D2R receptor interaction. Regarding Akt/GSK-3beta downstream targets,
      antipsychotics increased beta-catenin levels, whereas (+/-)-alpha-lipoic acid
      induced an elevation of mTOR activation. These results suggest (1) that the
      effect of antipsychotics on the Akt/GSK-3beta pathway in SH-SY5Y cells is
      reminiscent of their in vivo action, (2) that (+/-)-alpha-lipoic acid partially
      synergizes with antipsychotic drugs (APDs) on the same pathway, and (3) that the
      Akt/GSK-3beta signaling cascade is not involved in the preventive effect of (+/-)
      alpha-lipoic acid on antipsychotics-induced D2R upregulation.

PMID- 22975851
TI  - [Case of acute limbic encephalitis associated with SLE accompanied with anti
      glutamate receptor antibodies].
AB  - A 23-year-old woman was admitted to our hospital because of consciousness
      disturbance and convulsion, preceded by high fever, headache and erythema
      multiforme. Her brain magnetic resonance images showed hyperintense lesions in
      the left medial temporal lobe and the left pulvinar nucleus of the thalamus on
      fluid attenuated inversion recovery images. Analysis of cerebrospinal fluid
      showed mild pleocytosis, but DNA of herpes simplex or herpes type 6 viruses was
      negative on PCR. Laboratory investigations showed the presence of anti-nuclear
      antibodies, anti-RNP antibodies and lupus anticoagulant. The clinical diagnosis
      was made as acute limbic encephalitis associated with SLE, and subsequent
      administration of prednisolone improved her conditions. In her serum and
      cerebrospinal fluid, anti-glutamate receptor (epsilon2, delta2, zeta1) antibodies
      were detected, and the titers of the antibodies decreased as the symptoms
      improved. Although the mechanism underlying limbic encephalitis associated with
      SLE remains unclear, at least in some cases, the anti-glutamate antibodies may
      play an important role in the pathogenesis of limbic encephalitis with SLE.

PMID- 22975850
TI  - Striatal neuronal loss correlates with clinical motor impairment in Huntington's
      disease.
AB  - Huntington's disease (HD) is characterized clinically by chorea, motor
      impairment, psychiatric manifestations, and dementia. Atrophy of the striatum is
      the neuropathological hallmark of HD, and previous studies have suggested that
      striatal atrophy correlates more closely with motor impairment than with chorea.
      Motor impairment, as measured by motor impairment score, correlates with
      functional disability in HD patients, but chorea does not. In this study, we
      investigated the relation between neuronal loss and these motor features. We
      conducted neuropathological and stereologic assessments of neurons in putamen and
      subthalamic nuclei in HD patients and age-matched controls. In putamen, we
      estimated the total number and volume of medium spiny neurons labeled with
      dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32). In subthalamic
      nuclei, we estimated the total number of neurons on hematoxylin & eosin/luxol
      fast blue stains. In putamen of HD, immunohistochemistry showed DARPP-32 neuronal
      atrophy with extensive disruption of neurites and neuropil; stereologic studies
      found significant decreases in both the number and size of DARPP-32 neurons; we
      also detected a significant reduction of overall putamen volume in HD patients,
      compared to controls. In subthalamic nuclei, there was a mild, but significant,
      neuronal loss in the HD group. The loss of neurons in putamen and subthalamic
      nuclei as well as putaminal atrophy were significantly correlated with severity
      of motor impairment, but not with chorea. Our findings suggest that neuronal loss
      and atrophy in striatum and neuronal loss in subthalamic nuclei contribute
      specifically to the motor impairment of HD, but not to chorea.

PMID- 22975852
TI  - [Treatment of intractable tuberculous meningitis using intrathecal isoniazid
      administration and steroid pulse therapy; a report of two cases].
AB  - Tuberculous meningitis (TbM) is a neurological emergency condition that requires
      prompt initiation of treatment. The standard initial treatment for TbM is often
      insufficient for producing remission because the anti-tuberculosis agent may
      cause severe side effects, or vasculitis and hydrocephalus may induce an
      intractable state. Moreover, it is difficult to distinguish paradoxical expansion
      from its own deterioration. We treated 2 cases of adult TbM by using
      multidisciplinary therapy, including methyl prednisolone pulse and intrathecal
      isoniazid administration. Both cases had not been diagnosed as pulmonary or other
      tuberculosis, and cerebrospinal fluid (CSF) culture and polymerase chain reaction
      at approximately 1 week after hospitalization identified the cases as TbM. We
      administered the standard initial treatment recommended by the British Infection
      Society guidelines for adults, but both cases deteriorated and showed elevation
      of intracranial pressure. We indwelled a lumbar drainage for Case 1 and an Ommaya
      reservoir for Case 2. We removed CSF and administrated isoniazid regularly using
      each of the drainage devices, added streptomycin, and increased the steroid dose
      including addition of steroid pulse therapy. Both cases improved, and their
      neurological dysfunction did not persist. After the induction of an intractable
      state occurs due to TbM, we are likely to assume poor prognosis and neurological
      sequelae. However, our experience in these cases showed amelioration of the
      symptoms leading to the rehabilitation of these patients in society.

PMID- 22975853
TI  - [Case of post-anoxic reticular reflex myoclonus].
AB  - BACKGROUND: Reticular reflex myoclonus is a rare condition with only a few cases
      clearly documented on video. The purpose of this paper is to report a patient
      manifesting typical clinical picture documented on video and characteristic
      electrophysiological features of reticular reflex myoclonus. CASE: A 60-year-old
      woman presented with spontaneous and stimulus-sensitive myoclonic jerks involving
      the face, neck and upper extremities following anoxic episode. The patient was
      investigated electrophysiologically. Surface electromyogram showed brief
      myoclonic activity starting from the sternocleidomastoid and spreading up to the
      orbicularis oculi as well as down to the upper limb muscles. Cortical
      somatosensory evoked potentials and long-latency reflex were not enhanced.
      CONCLUSION: Clinical features and electrophysiological findings of this case are
      consistent with those of reticular reflex myoclonus originally reported by
      Hallett et al. in 1977.

PMID- 22975854
TI  - [Case of adult onset vanishing white matter disease developed after minor head
      trauma].
AB  - A 20-year-old previously healthy man presented with prolonged consciousness
      alteration and severe hypertonia in the extremities after minor head trauma.
      Laboratory blood tests and cerebrospial fluid (CSF) tests were unremarkable
      except for an elevated CSF glycine concentratons. Brain MRI revealed hypoplasia
      of corpus callosum, enlargement of lateral cerebral ventricle and high signal
      intensity in the bilateral white matter on T(2) weighted images. On fluid
      attenuated inversion recovery images, the signal intensity resembled that of CSF
      in the central areas of T(2) alterations, surrounded by a rim of hyperintensity.
      These characteristic history and the results of brain MRI and CSF, the diagnosis
      of vanishing white matter disease (VWMD) was made. VWMD is a rare autosomal
      recessive leukoencephalopathy which typically begins during infancy or early
      childhood with a chronic progressive neurological deterioration with cerebellar
      ataxia and spasticity. Recently, milder variants of the disease with adult onset
      have been reported. VWMD should be included in the differential diagnosis of
      leucoencephalopathy in young adults.

PMID- 22975855
TI  - [Reversible posterior leukoencephalopathy syndrome (RPLS) associated with
      Wegener's granulomatosis: a case report and review of the literature].
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by
      sudden onset of headaches, visual disorders, decreased consciousness, and
      convulsion associated with brain edema occurring in the occipital lobe. Several
      different causes including malignant hypertension, eclampsia, renal failure, and
      use of immunosuppressants have been reported in patients with RPLS. Our patient
      was a 45-year-old man who presented with fever, arthralgia, and melena
      approximately 1 year previously and received the diagnosis of Wegener's
      granulomatosis. Following steroid therapy his symptoms ameliorated; however,
      during the course of the illness he developed tension-type headache, nausea and
      vomiting, and bilateral loss of visual acuity. On admission, his visual acuity
      was markedly decreased without any abnormal findings in the optic fundus. There
      was no neurological deficit except the visual symptoms. Imaging of the head
      revealed multiple lesions in the white and gray matter of the bilateral occipital
      lobe and cerebellar hemisphere, which proved vasogenic edematous lesions by the
      hyperintense signals in T(2) weighted, FLAIR, and diffusion weighted images,
      suggesting the diagnosis of RPLS. Treatment with antihypertensive drug and
      glycerol was initiated and the patient made a full clinical recovery within a few
      days. The pathogenesis of RPLS is not fully understood. Our case was not on any
      immunosuppressant therapy at the time of onset of RPLS, and his hypertension was
      mild and transient without renal failure. It is possible that RPLS in our patient
      might be a manifestation related to Wegener's granulomatosis-mediated vascular
      endothelial injury.

PMID- 22975856
TI  - [Case of recurrent encephalomyelitis associated with eosinophilia in CSF].
AB  - We report a 30-year-old man with recurrent eosinophilic encephalomyelitis. He had
      a history of childhood asthma and allergic rhinitis. A half year before
      admission, when he suffered from a headache, a few lesions were indicated by
      brain MRI at another hospital. From a month before admission, he noticed gait
      disturbance, sensory impairment, difficulty in micturition, and constipation.
      Neurological examination revealed moderate muscle weakness in the feet,
      hypoesthesia below Th6, and bladder-bowel disturbance including impotence. Lumbar
      T(2) weigthed MRI showed a severe swelling and a hyperintense lesion at the conus
      medullaris. Brain MRI revealed several asymptomatic white matter lesions.
      Eosinophilia was documented in the cerebrospinal fluid (CSF) but not in the
      peripheral blood. Clinical symptoms and MRI findings were remarkably improved
      after steroid pulse therapy. Note that eosinophils in the CSF were also decreased
      after the treatment with apoptosis-like cells. We thought that CSF eosinophilia
      was the core pathogenic feature of this case, but clinical settings that provoke
      CSF eosinophilia such as parasites and other infectious agents, neuromyelitis
      optica, atopic myelitis, eosinophilic leukemia and hypereosinophilic syndrome
      could be ruled out. The remarkable responses to steroids without any additional
      therapy, compatible with idiopathic eosinophilic syndromes, confirmed that this
      was a case of idiopathic eosinophilic recurrent encephalomyelitis.

PMID- 22975857
TI  - [A 34-year-old woman with cat scratch disease who developed encephalopathy].
AB  - We experienced a patient with cat-scratch disease (CSD) who developed
      encephalopathy. The subject was a 34-year-old female who had been aware of a low
      grade fever and swollen inguinal lymph nodes for 1 month. The subject's
      consciousness became impaired after a headache developed, accompanied by fever,
      nausea, and vomiting, and she subsequently sought medical consultation. No major
      abnormalities were observed in the cerebrospinal fluid and cranial magnetic
      resonance imaging (MRI) was normal. However, necrotizing lymphadenitis was
      observed on contrast enhanced computed tomography (CT) of the pelvis and
      granulomatous changes were observed in a surgical lymph node biopsy. As the
      subject lived with a pet cat, PCR testing for Bartonella henselae (the CSD
      pathogen) was performed using a tissue biopsy. This was positive and the subject
      was diagnosed with CSD encephalopathy. There are very few domestic reports of CSD
      encephalopathy and care must be taken not to overlook this disease.

PMID- 22975858
TI  - [Case of acquired hepatocerebral degeneration with prominent improvement of
      parkinsonism and cognitive deficits after living-donor liver transplantation].
AB  - A 53-year-old woman visited us for a neurological consultation before her liver
      transplantation. She had a history of primary biliary cirrhosis that began at 37
      years of age. She showed falling episodes and met with a traffic accident at 52
      years old. Since then, her symptoms had worsened. The neurological examination
      showed masked face, rigidity on bilateral arms and legs, and lack of balance. Her
      Mini-Mental State Examination Score was 28/30, but she suffered from loss of
      memory and had trouble with executive function in detailed examinations. Her T(1)
      weighted image showed hyperintensity in bilateral globus pallidus, putamen,
      dentate nucleus and cerebral peduncle. There was a significant improvement in
      intellectual function and neurological signs 6 months after her orthotopic liver
      transplantation. In addition, post-liver transplantation images showed a decrease
      in the area of hyperintensities. This case suggests that even in a patient with
      severe liver cirrhosis a complete cure of neurological manifestations can be
      obtained after the liver transplantation.

PMID- 22975859
TI  - [Cerebral amyloid angiopathy-related leukodystrophy: a case report].
AB  - An 86-year-old woman was admitted following generalized seizure. Postictally she
      showed disturbance of consciousness, right hemiparesis, and right spatial
      neglect. Brain fluid attenuated inversion recovery (FLAIR) imaging demonstrated
      mainly left-sided, but asymmetrical, subcortical white matter lesions. On the
      second day, level of consciousness improved, along with right hemiparesis and
      right spatial neglect. Electroencephalography displayed mainly alpha waves and
      sporadic theta waves without sharp waves. One week later, however, the patient
      again experienced somnolence and right hemiparesis. FLAIR revealed day-by-day
      enlargement of white matter lesions. The possibilities of hypoglycemia,
      hyperammonemia, hypothyroidism, Hashimoto encephalopathy, collagen disease,
      antineutrophil cytoplasmic antibody-related angiitis, and infection were excluded
      based on the results of blood biochemistry and cerebrospinal fluid. We initially
      suspected intravascular lymphoma, so random skin biopsy was performed, but the
      results were negative. We then suspected cerebral amyloid angiopathy because of
      the presence of dementia and multiple microbleeds on T(2)* weighted magnetic
      resonance imaging. Cerebral biopsy revealed amyloid deposition in cortical
      arterioles and CD3-positive T cells in the perivascular space. Cerebral amyloid
      angiopathy-related leukodystrophy was therefore diagnosed and immunosuppressive
      treatment was started. After 14 days of treatment, clinical symptoms and results
      of FLAIR imaging were significantly improved. When patients display asymmetrical
      subcortical white matter lesions with microbleeds on T(2)* weighted imaging,
      amyloid angiopathy-related inflammation should be considered.

PMID- 22975860
TI  - [Neurolymphomatosis presenting as bilateral tongue atrophy: a case report].
AB  - A 62-year-old woman had progressive dysarthria for 2 months and was suspected of
      having amyotrophic lateral sclerosis because of the presentation of bilateral
      tongue atrophy and fasciculation. Brain magnetic resonance imaging (MRI) showed
      enlargement of the left hypoglossal nerve, and whole-body gallium scintigraphy
      showed abnormal uptake in the left pelvic cavity and left thigh. On the basis of
      the findings of biopsy of the mass lesion in the left thigh, she was diagnosed
      with diffuse large B-cell lymphoma. After chemotherapy for diffuse large B-cell
      lymphoma, the tongue atrophy improved. The patient subsequently developed left
      oculomotor nerve palsy, weakness of the right arm, and weakness of the right leg.
      The cause of these symptoms was thought to be neurolymphomatosis on the basis of
      the typical MRI findings observed. We report a rare case of neurolymphomatosis
      presenting as bilateral tongue atrophy, mimicking amyotrophic lateral sclerosis.

PMID- 22975861
TI  - In vivo modulation of the inflammatory response by nonsteroidal antiinflammatory
      drug-related compounds that trigger L-selectin shedding.
AB  - Diphenylamine-based nonsteroidal antiinflammatory drugs (NSAIDs) are able to
      cause in vitro the shedding of L-selectin. The aim of this work was to determine
      the physio-logic relevance of L-selectin shedding in the antiinflammatory effect
      exerted by NSAIDs in vivo. Chemical compounds structurally related to NSAIDs -
      including diphenyl-amine, N-phenylanthranilic acid (N-Ph), diphenylacetic acid -
      as well as the traditional NSAID indomethacin were studied using the zymosan air
      pouch mouse model. Animals intramuscularly pretreated with indomethacin or N-Ph,
      but not with diphenyl-amine or diphenylacetic acid, showed a significant dose
      dependent reduction in the number of neutrophils compared with untreated animals
      (N-Ph, IC50 = 6.7 mg/kg). Except for indomethacin, none of these compounds caused
      any significant reduction in cyclooxygenase-1 activity in vivo. In flow chamber
      experiments, N-Ph reduced the capability of human neutrophils to pass across the
      endothelial barrier by interfering with leukocyte rolling step on HUVEC. N-Ph,
      but not diphenylacetic acid, induced activation-independent L-selectin shedding
      in mouse neutrophils. Interestingly, N-Ph exerted an antiinflammatory effect
      similar to that of the anti-L-selectin blocking antibody Mel-14, although no
      additive action was observed when both compounds were combined. These data
      suggest that the L-selectin shedding induced by NSAIDs may be involved in the
      antiinflammatory action exerted by these compounds in clinical settings.

PMID- 22975863
TI  - A simple decision analytic solution to the comparison of two binary diagnostic
      tests.
AB  - One of the most basic biostatistical problems is the comparison of two binary
      diagnostic tests. Commonly, one test will have greater sensitivity, and the other
      greater specificity. In this case, the choice of the optimal test generally
      requires a qualitative judgment as to whether gains in sensitivity are offset by
      losses in specificity. Here, we propose a simple decision analytic solution in
      which sensitivity and specificity are weighted by an intuitive parameter, the
      threshold probability of disease at which a patient will opt for treatment. This
      gives a net benefit that can be used to determine which of two diagnostic tests
      will give better clinical results at a given threshold probability and whether
      either is superior to the strategy of assuming that all or no patients have
      disease. We derive a simple formula for the relative diagnostic value, which is
      the difference in sensitivities of two tests divided by the difference in the
      specificities. We show that multiplying relative diagnostic value by the odds at
      the prevalence gives the odds of the threshold probability below which the more
      sensitive test is preferable and above which the more specific test should be
      chosen. The methodology is easily extended to incorporate combinations of tests
      and the risk or side effects of a test.

PMID- 22975862
TI  - A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and
      ROS production.
AB  - In cancer-treatment, potentially therapeutic drugs trigger their effects through
      apoptotic mechanisms. Generally, cell response is manifested by Bcl-2 family
      protein regulation, the impairment of mitochondrial functions, and ROS
      production. Notwithstanding, several drugs operate through proteasome inhibition,
      which, by inducing the accumulation and aggregation of misfolded or unfolded
      proteins, can lead to endoplasmic reticulum (ER) stress. Accordingly, it was
      shown that Amblyomin-X, a Kunitz-type inhibitor identified in the transcriptome
      of the Amblyomma cajennense tick by ESTs sequence analysis of a cDNA library,
      obtained in recombinant protein form, induces apoptosis in murine renal
      adenocarcinoma (RENCA) cells by: inducing imbalance between pro- and anti
      apoptotic Bcl-2 family proteins, dysfunction/mitochondrial damage, production of
      reactive oxygen species (ROS), caspase cascade activation, and proteasome
      inhibition, all ER-stress inductive. Moreover, there was no manifest action on
      normal mouse-fibroblast cells (NHI3T3), suggesting an Amblyomin-X tumor-cell
      selectivity. Taken together, these evidences indicate that Amblyomin-X could be a
      promising candidate for cancer therapy.

PMID- 22975864
TI  - The role of the right dorsolateral prefrontal cortex in the Tower of London task
      performance: repetitive transcranial magnetic stimulation study in patients with
      Parkinson's disease.
AB  - We studied whether one session of high-frequency repetitive transcranial magnetic
      stimulation (rTMS) applied over either the right or left dorsolateral prefrontal
      cortex would induce any measurable changes in the Tower of London spatial
      planning task performance in patients with Parkinson's disease (PD). Ten patients
      with PD (with no dementia and/or depression) entered the randomized, sham
      stimulation-controlled study with a crossover design. Active and placebo rTMS
      were applied over either the left or the right dorsolateral prefrontal cortex (in
      four separate sessions) in each patient. The order of sessions was randomized.
      The Tower of London task was performed prior to and immediately after each
      appropriate session. The "total problem-solving time" was our outcome measure.
      Only active rTMS of the right dorsolateral prefrontal cortex induced significant
      enhancement of the total problem-solving time, p = 0.038. Stimulation of the left
      prefrontal cortex or sham stimulations induced no significant effects. Only rTMS
      applied over the right dorsolateral prefrontal cortex induced positive changes in
      the spatial planning task performance in PD, which further supports the results
      of functional imaging studies indicating the causal engagement of the right-sided
      hemispheric structures in solving the task in this patient population.

PMID- 22975866
TI  - Traumatic intracranial aneurysms due to blunt brain injury-a single center
      experience.
AB  - BACKGROUND: Traumatic intracranial aneurysms (TICAs) have previously been
      described in literature. However, the evidence of TICAs secondary to blunt brain
      injury have not been elucidated well, with most of the conclusions coming from
      isolated case reports. We have attempted to examine the epidemiology,
      classification, clinical presentation, therapeutic modalities, and outcomes of
      TICAs with our series of patients at the neurosurgery department of Xuanwu
      Hospital, China. METHODS: We reviewed our aneurysm database from January 1, 2005
      to December 31, 2011. In particular, patients with TICAs secondary to blunt brain
      injury were reviewed. Variables assessed included age, sex, causes of blunt brain
      injury, skull fracture, location, classification, clinical presentation, time
      elapsed to arrive at diagnoses, treatment, and eventual outcome. Based on our
      assessment, we arrived at a modified classification scheme to categorize these
      aneurysms. RESULTS: We reviewed 2335 patients with cerebral aneurysm from January
      1, 2005 to December 31, 2011. Of these, 15 patients (0.64 %) with traumatic
      aneurysms secondary to blunt brain injury were identified.Motor vehicle accidents
      (MVA) were observed to be the most common cause of injury (10 patients, 66.7 %),
      followed by TICAs sustained after falling down (5 patients, 33.3 %). The most
      common symptom at presentation was epistaxis (6 patients, 40 %), followed by
      ophthalmic problems (6 patients, 40 %), with both presentations seen in 1
      patient. The most common diagnostic modality used was DSA in 12 patients (80 %)
      followed by CTA in 2 patients (13.3 %). Infraclinoid TICAs were seen in 9
      patients (60 %), whereas supraclinoid TICAs were seen in 5 patients (33.3 %),
      with perifalx TICAs seen in 1 patient. Endovascular intervention therapies were
      performed in 11 patients (73.3 %), bypass surgery and trapping in 2 (13.3 %),
      transnasal endoscopic approach in combination with balloon assisted in 2
      patients. At discharge, 2 patients had poor clinical outcomes (13.3 %), 5 had
      fair (33.3 %),and 8 resulted with good outcomes (53.3 %). CONCLUSIONS: TICAs
      arising secondary to blunt brain injury account for 0.64 % of all cerebral
      aneurysms. Infraclinoid, supraclinoid ICA and perifalx TICAs are the most common
      aneurysms arising from blunt brain injury. Our study further shows that traumatic
      patients presenting with recurrent epistaxis, oculomotor nerve palsy, and delayed
      intracranial hemorrhage should receive cerebroangiography as soon as possible. An
      early diagnosis and proper treatment could prove to be helpful in terms of
      improving final clinical outcome.

PMID- 22975865
TI  - The influence of spatial working memory on ipsilateral remembered proprioceptive
      matching in adults with cerebral palsy.
AB  - Somatosensation is frequently impaired in individuals with Cerebral Palsy (CP).
      This includes the sense of proprioception, which is an important contributor to
      activities of daily living. One means of determining proprioceptive deficits in
      CP has been use of an Ipsilateral Remembered (IR) position matching test. The IR
      test requires participants to replicate, without vision, memorized joint/limb
      positions previously experienced by the same (i.e. ipsilateral) effector. Given
      the memory component inherent to this task, the present study sought to determine
      the extent to which IR proprioceptive matching might be influenced by known
      spatial working memory deficits. Eleven adults with CP underwent IR elbow
      position matching, where blindfolded individuals were given either a short (2 s)
      or long (15 s) duration to memorize the target elbow angle. A standard clinical
      measure of spatial working memory (i.e. Corsi block-tapping task) was also
      administered. The results showed that the directional (i.e. constant) error
      produced across trials did not differ between the short and long target duration
      conditions. However, it was found that participants were significantly more
      consistent in their matches (i.e. had smaller variable errors) when given more
      time to encode proprioceptive targets in the long duration condition. The benefit
      of having more time was greatest for those individuals with the highest variable
      errors in the short target condition, and a significant association was seen
      between improvements in variable error and greater performance on 4/5 spatial
      working memory measures. These findings provide the best evidence to date that IR
      position matching tests are influenced by spatial working memory.

PMID- 22975867
TI  - Outer diameter measured by 3D CISS MRI and quasi-Moyamoya disease.

PMID- 22975868
TI  - DNA confinement in nanochannels: physics and biological applications.
AB  - DNA is the central storage molecule of genetic information in the cell, and
      reading that information is a central problem in biology. While sequencing
      technology has made enormous advances over the past decade, there is growing
      interest in platforms that can readout genetic information directly from long
      single DNA molecules, with the ultimate goal of single-cell, single-genome
      analysis. Such a capability would obviate the need for ensemble averaging over
      heterogeneous cellular populations and eliminate uncertainties introduced by
      cloning and molecular amplification steps (thus enabling direct assessment of the
      genome in its native state). In this review, we will discuss how the information
      contained in genomic-length single DNA molecules can be accessed via physical
      confinement in nanochannels. Due to self-avoidance interactions, DNA molecules
      will stretch out when confined in nanochannels, creating a linear unscrolling of
      the genome along the channel for analysis. We will first review the fundamental
      physics of DNA nanochannel confinement--including the effect of varying ionic
      strength--and then discuss recent applications of these systems to genomic
      mapping. Apart from the intense biological interest in extracting linear sequence
      information from elongated DNA molecules, from a physics view these systems are
      fascinating as they enable probing of single-molecule conformation in
      environments with dimensions that intersect key physical length-scales in the 1
      nm to 100 um range.

PMID- 22975869
TI  - The effect of calcination temperature on the microstructure and photocatalytic
      activity of TiO2-based composite nanotubes prepared by an in situ template
      dissolution method.
AB  - TiO(2)-based composite nanotubes, based on an in situ template dissolution
      method, were one-step fabricated in a mixed aqueous solution of ammonium
      hexafluorotitanate and boric acid using ZnO nanorods as templates, and then the
      samples were calcined at different temperatures. The photocatalytic activity of
      the samples was evaluated by photocatalytic decoloration of Methyl Orange (MO)
      aqueous solution at ambient temperature under UV light. The results showed that
      the prepared sample possessed nanoscale tubular morphology with a wall thickness
      of ca. 30-50 nm, inner diameters of ca. 50-150 nm and lengths of ca. 400-2000 nm.
      The calcined samples exhibited excellent stabilization of the anatase phase in a
      wide temperature range of 300-800  degrees C. The un-calcined and calcined
      samples possessed hierarchically macro-mesoporous structures. The sample calcined
      at 600  degrees C exhibited the highest photocatalytic activity, corresponding to
      the maximal formation rate of OH on the photocatalyst. This is attributed to the
      improvement of anatase TiO(2) crystallization, the formation of multi-phase
      structures including anatase, cubic Zn(2)TiO(4), hexagonal ZnTiO(3) and cubic
      ZnTiO(3), and the presence of hierarchically macro-mesoporous structures.

PMID- 22975870
TI  - Immunobiology of dendritic cells and the influence of HIV infection.
AB  - Recent progress in phenotyping of human dendritic cells (DCs) has allowed a
      closer alignment of the classification and functions of murine and human
      dendritic cell subsets. Marked differences in the functions of these human DC
      subsets and their response to HIV infection have become apparent, relevant to HIV
      pathogenesis and vaccine and microbicide development. Systems biology approaches
      to studying HIV uptake and infection of dendritic cells has revealed how markedly
      HIV subverts their functions, especially in relation to the trafficking pathways
      and viral transfer to T cells. Furthermore the interactions between DCs and other
      innate immune cells, NK cells, NKT cells and gamma delta T cells are now known to
      influence DC and T cell function and are also disturbed by HIV infection in vitro
      and in vivo. Such cellular interactions are potential targets for vaccine
      adjuvants and immunotherapy.

PMID- 22975871
TI  - Antiviral immune responses by human langerhans cells and dendritic cells in HIV-1
      infection.
AB  - The main route of human immunodeficiency virus-1 (HIV-1) infection is via
      unprotected sexual intercourse, and therefore, vaginal tissues and male foreskin
      are viral entry sites. Langerhans cells (LCs) and dendritic cells (DCs) are
      amongst the first immune cells encountering HIV-1 since these cells line these
      mucosal tissues. Both LCs and DCs are equipped with specific pattern recognition
      receptors that not only sense pathogens, but induce specific immune responses
      against these pathogens. LCs express the C-type lectin receptor langerin, which
      provides protection against HIV-1 infection. In contrast, DCs express the C-type
      lectin receptor DC-SIGN, which facilitates capture as well as infection of DCs
      and subsequent transmission to CD4(+) T cells. This chapter gives an update on
      immune responses elicited against viruses and sheds a light on different immune
      mechanisms that are hijacked by HIV-1 to infect the host. HIV-1 infection
      ultimately leads to the worldwide pandemic acquired immunodeficiency syndrome
      (AIDS).

PMID- 22975873
TI  - Cellular and viral mechanisms of HIV-1 transmission mediated by dendritic cells.
AB  - Dendritic cells (DCs) play a key role in the initial infection and cell-to-cell
      transmission events that occur upon HIV-1 infection. DCs interact closely with
      CD4(+) T cells, the main target of HIV-1 replication. HIV-1 challenged DCs and
      target CD4(+) T cells form a virological synapse that allows highly efficient
      transmission of HIV-1 to the target CD4(+) T cells, in the absence of productive
      HIV-1 replication in the DCs. Immature and subsets of mature DCs show distinct
      patterns of HIV-1 replication and cell-to-cell transmission, depending upon the
      maturation stimulus that is used. The cellular and viral mechanisms that promote
      formation of the virological synapse have been the subject of intense study and
      the most recent progress is discussed here. Characterizing the cellular and viral
      factors that affect DC-mediated cell-to-cell transmission of HIV-1 to CD4(+) T
      cells is vitally important to understanding, and potentially blocking, the
      initial dissemination of HIV-1 in vivo.

PMID- 22975872
TI  - Plasmacytoid dendritic cells in HIV infection.
AB  - Plasmacytoid dendritic cells (pDCs) are innate immune cells that are specialized
      to produce interferon-alpha (IFNalpha) and participate in activating adaptive
      immune responses. Although IFNalpha inhibits HIV-1 (HIV) replication in vitro,
      pDCs may act as inflammatory and immunosuppressive dendritic cells (DCs) rather
      than classical antigen-presenting cells during chronic HIV infection in vivo,
      contributing more to HIV pathogenesis than to protection. Improved understanding
      of HIV-pDC interactions may yield potential new avenues of discovery to prevent
      HIV transmission, to blunt chronic immune activation and exhaustion, and to
      enhance beneficial adaptive immune responses. In this chapter we discuss pDC
      biology, including pDC development from progenitors, trafficking and localization
      of pDCs in the body, and signaling pathways involved in pDC activation. We focus
      on the role of pDCs in HIV transmission, chronic disease progression and immune
      activation, and immunosuppression through regulatory T cell development. Lastly,
      we discuss potential future directions for the field which are needed to
      strengthen our current understanding of the role of pDCs in HIV transmission and
      pathogenesis.

PMID- 22975876
TI  - Interactions between HIV-1 and innate immunity in dendritic cells.
AB  - Dendritic cells couple pathogen sensing with induction of innate and adaptive
      immune responses. Pathogen sensing in dendritic cells relies on interactions
      between molecular patterns of the pathogens and germline-encoded, also referred
      to as innate, receptors. In this chapter, we analyze some of the interactions
      between HIV-1 and the innate immune system in dendritic cells. The HIV-1
      replication cycle is constituted by an extracellular and an intracellular phase.
      The two phases of the cycle provide distinct opportunities for interactions with
      cell-extrinsic and cell-intrinsic mechanisms in dendritic cells. According to the
      types of dendritic cells, the mechanisms of innate interactions between dendritic
      cells and HIV-1 lead to specific responses. These innate interactions may
      contribute to influencing and shaping the adaptive immune response against the
      virus.

PMID- 22975874
TI  - Role of glycosphingolipids in dendritic cell-mediated HIV-1 trans-infection.
AB  - Glycosphingolipids (GSLs) are components of the cell membrane that comprise a
      membrane bound lipid, ceramide, coupled to an extracellular carbohydrate. GSLs
      impact numerous aspects of membrane biology, including membrane fluidity,
      curvature, and organization. The role of these molecules in both chronic
      inflammation and infectious disease and underlying pathogenic mechanisms are just
      starting to be recognized. As a component of the cell membrane, GSLs are also
      incorporated into lipid bilayers of diverse enveloped viruses as they bud out
      from the host cell and can go on to have a significant influence on viral
      pathogenesis. Dendritic cell (DC) subsets located in the peripheral mucosal
      tissues are proposed to be one of the earliest cell types that encounter
      transmitted viruses and help initiate adaptive immune responses against the
      invading pathogen by interacting with T cells. In turn, viruses, as obligatory
      intracellular parasites, rely on host cells for completing their replication
      cycle, and not surprisingly, HIV has evolved to exploit DC biology for the
      initial transmission event as well as for its dissemination and propagation
      within the infected host. In this review, we describe the mechanisms by which
      GSLs impact DC-mediated HIV trans-infection by either modulating virus
      infectivity, serving as a direct virus particle-associated host-derived ligand
      for specific interactions with DCs, or modulating the T cell membrane in such a
      way as to impact viral entry and thereby productive infection of CD4(+) T cells.

PMID- 22975877
TI  - HIV impairment of immune responses in dendritic cells.
AB  - Dendritic cells and their subsets are diverse populations of immune cells in the
      skin and mucous membranes that possess the ability to sense the presence of
      microbes and orchestrate an efficient and adapted immune response. Dendritic
      cells (DC) have the unique ability to act as a bridge between the innate and
      adaptive immune responses. These cells are composed of a number of subsets
      behaving with preferential and specific features depending on their location and
      surrounding environment. Langerhans cells (LC) or dermal DC (dDC) are readily
      present in mucosal areas. Other DC subsets such as plasmacytoid DC (pDC), myeloid
      DC (myDC), or monocyte-derived DC (MDDC) are thought to be recruited or
      differentiated in sites of pathogenic challenge. Upon HIV infection, DC and their
      subsets are likely among the very first immune cells to encounter incoming
      pathogens and initiate innate and adaptive immune responses. However, as
      evidenced during HIV infection, some pathogens have evolved subtle strategies to
      hijack key cellular machineries essential to generate efficient antiviral
      responses and subvert immune responses for spread and survival.In this chapter,
      we review recent research aimed at investigating the involvement of DC subtypes
      in HIV transmission at mucosal sites, concentrating on HIV impact on cellular
      signalling and trafficking pathways in DC leading to DC-mediated immune response
      alterations and viral immune evasion. We also address some aspects of DC
      functions during the chronic immune pathogenesis and conclude with an overview of
      the current and novel therapeutic and prophylactic strategies aimed at improving
      DC-mediated immune responses, thus to potentially tackle the early events of
      mucosal HIV infection and spread.

PMID- 22975878
TI  - HIV-derived vectors for gene therapy targeting dendritic cells.
AB  - Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have
      the potential to mediate stable therapeutic gene transfer. However, similarly to
      other viral vectors, their benefit is compromised by the induction of an immune
      response toward transgene-expressing cells that closely mimics antiviral
      immunity. LV share with the parental HIV the ability to activate dendritic cells
      (DC), while lack the peculiar ability of subverting DC functions, which is
      responsible for HIV immune escape. Understanding the interaction between LV and
      DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has
      paved the way to novel approaches aimed at regulating transgene-specific immune
      responses. Thanks to the ability to target either DC subsets LV might be a
      powerful tool to induce immunity (i.e., gene therapy of cancer), cell death
      (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for
      monogenic diseases). In this chapter, similarities and differences between the LV
      mediated and HIV-mediated induction of immune responses, with specific focus on
      their interactions with DC, are discussed.

PMID- 22975875
TI  - Simian immunodeficiency virus interactions with macaque dendritic cells.
AB  - This chapter summarizes advances in the following areas: (1) dendritic cell (DC)
      mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in
      innate and adaptive immunity against SIV, and (3) approaches to harness DC
      function to induce anti-SIV responses. The nonhuman primate (NHP) model of human
      immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP
      species is highly relevant to advance the understanding of virus-host
      interactions critical for transmission and disease pathogenesis. HIV infection is
      associated with changes in frequency, phenotype, and function of the two
      principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during
      pathogenic SIV infection is strikingly similar to that observed in HIV-infected
      patients. The NHP models provide an opportunity to dissect the requirements for
      DC-driven SIV infection and to understand how SIV distorts the DC system to its
      advantage. Furthermore, the SIV model of mucosal transmission enables the study
      of the earliest events of infection at the portal of entry that cannot be studied
      in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in
      African NHP hosts allows investigations into the role of DCs in disease control.
      Understanding how DCs are altered during SIV infection is critical to the design
      of therapeutic and preventative strategies against HIV.

PMID- 22975879
TI  - Targeting dendritic cells for improved HIV-1 vaccines.
AB  - As dendritic cells (DCs) have the unique capacity to activate antigen-naive T
      cells they likely play a critical role in eliciting immune responses to vaccines.
      DCs are therefore being explored as attractive targets for vaccines, but
      understanding the interaction of DCs and clinically relevant vaccine antigens and
      adjuvants is a prerequisite. The HIV-1/AIDS epidemic continues to be a
      significant health problem, and despite intense research efforts over the past 30
      years a protective vaccine has not yet been developed. A common challenge in
      vaccine design is to find a vaccine formulation that best shapes the immune
      response to protect against and/or control the given pathogen. Here, we discuss
      the importance of understanding the diversity, anatomical location and function
      of different human DC subsets in order to identify the optimal target cells for
      an HIV-1 vaccine. We review human DC interactions with some of the HIV-1 vaccine
      antigen delivery vehicles and adjuvants currently utilized in preclinical and
      clinical studies. Specifically, the effects of distinctly different vaccine
      adjuvants in terms of activation of DCs and improving DC function and vaccine
      efficacy are discussed. The susceptibility and responses of DCs to recombinant
      adenovirus vectors are reviewed, as well as the strategy of directly targeting
      DCs by using DC marker-specific monoclonal antibodies coupled to an antigen.

PMID- 22975880
TI  - Physician communication and physical activity among Latinas.
AB  - BACKGROUND: Research suggests that individuals who talk with their physicians
      about lifestyle behaviors are more physically active. Research on this topic is
      limited in the U.S. Latino population. This study examines doctor-patient
      communication from the perspective of enrollees in a physical activity (PA)
      intervention. METHODS: Three hundred and eighty-seven Latinos were surveyed at
      program enrollment. Analysis examined the extent to which physician communication
      about healthy lifestyles and weight was associated with self-reported PA,
      including leisure-time PA (LTPA), transportation PA (TPA), and occupational PA
      (OPA). Physician communication included asking, advising, and assisting. RESULTS:
      Most of the respondents reported no LTPA (46%) and no TPA (60%). The percent
      reporting no occupational activity, which included housework if a homemaker, was
      lower at 36%. Greater physician assistance was associated with a greater
      likelihood of doing any LTPA (P <= .05). A similar trend was observed for TPA (P
      <= .10). CONCLUSIONS: Latinos who reported physician assistance to engage in
      healthy lifestyle behaviors reported more LTPA. Providers who assist their
      patients in obtaining resources to support PA have the potential to increase
      levels of PA.

PMID- 22975881
TI  - An observational study of psychotropic drug use and initiation in older patients
      resident in their own home or in care.
AB  - OBJECTIVE: to compare the prescription of psychotropic medications for patients
      living in care homes with that for patients living at home. DESIGN AND SETTING:
      retrospective population database study in the Tayside region of Scotland.
      SUBJECTS: 70,297 patients aged >=65 and followed until death or the end of the
      study. METHODS: examining registered addresses for all people aged 65-99
      identified those in care. The prescriptions for a 12-week period was examined and
      psychotropic drug use compared by their place of residence. Comparisons of
      prescriptions pre- and post-admission were performed for people admitted to a
      care home from Jan 2005 to Dec 2006. RESULTS: people living in care (4.1%)
      received 9.80 more prescribed items (P < 0.001) from 1.63 more British National
      Formulary (BNF) categories (P < 0.001) than people living at home over a 12-week
      period. They were more likely to receive any psychotropic medication (42 versus
      16%, odds ratio (OR) 3.09, 95% CI: 2.79-3.41). Over 70% of 1,715 people admitted
      to care homes during the study who received psychotropic medication commenced the
      medication prior to admission. Patients who started anti-psychotics in the 30
      days prior to admission were less likely to have stopped them (OR: 0.53, 95% CI:
      0.30-0.94). CONCLUSION: prolonged prescription of psychotropic medications is
      commonplace in care home residents. Almost half of the people prescribed
      antipsychotic drugs received them for a minimum of 6 months. Systematic
      medication reviews must be established in all care homes to promote safe and
      effective prescription to this at-risk population.

PMID- 22975882
TI  - Microbial communities in the subglacial waters of the Vatnajokull ice cap,
      Iceland.
AB  - Subglacial lakes beneath the Vatnajokull ice cap in Iceland host endemic
      communities of microorganisms adapted to cold, dark and nutrient-poor waters, but
      the mechanisms by which these microbes disseminate under the ice and colonize
      these lakes are unknown. We present new data on this subglacial microbiome
      generated from samples of two subglacial lakes, a subglacial flood and a lake
      that was formerly subglacial but now partly exposed to the atmosphere. These data
      include parallel 16S rRNA gene amplicon libraries constructed using novel primers
      that span the v3-v5 and v4-v6 hypervariable regions. Archaea were not detected in
      either subglacial lake, and the communities are dominated by only five bacterial
      taxa. Our paired libraries are highly concordant for the most abundant taxa, but
      estimates of diversity (abundance-based coverage estimator) in the v4-v6
      libraries are 3-8 times higher than in corresponding v3-v5 libraries. The
      dominant taxa are closely related to cultivated anaerobes and microaerobes, and
      may occupy unique metabolic niches in a chemoautolithotrophic ecosystem. The
      populations of the major taxa in the subglacial lakes are indistinguishable (>99%
      sequence identity), despite separation by 6 km and an ice divide; one taxon is
      ubiquitous in our Vatnajokull samples. We propose that the glacial bed is
      connected through an aquifer in the underlying permeable basalt, and these
      subglacial lakes are colonized from a deeper, subterranean microbiome.

PMID- 22975883
TI  - A review of medical image watermarking requirements for teleradiology.
AB  - Teleradiology allows medical images to be transmitted over electronic networks
      for clinical interpretation and for improved healthcare access, delivery, and
      standards. Although such remote transmission of the images is raising various new
      and complex legal and ethical issues, including image retention and fraud,
      privacy, malpractice liability, etc., considerations of the security measures
      used in teleradiology remain unchanged. Addressing this problem naturally
      warrants investigations on the security measures for their relative functional
      limitations and for the scope of considering them further. In this paper,
      starting with various security and privacy standards, the security requirements
      of medical images as well as expected threats in teleradiology are reviewed. This
      will make it possible to determine the limitations of the conventional measures
      used against the expected threats. Furthermore, we thoroughly study the
      utilization of digital watermarking for teleradiology. Following the key
      attributes and roles of various watermarking parameters, justification for
      watermarking over conventional security measures is made in terms of their
      various objectives, properties, and requirements. We also outline the main
      objectives of medical image watermarking for teleradiology and provide
      recommendations on suitable watermarking techniques and their characterization.
      Finally, concluding remarks and directions for future research are presented.

PMID- 22975884
TI  - Nightshift work job exposure matrices and urinary 6-sulfatoxymelatonin levels
      among healthy Chinese women.
AB  - OBJECTIVE: Six-sulfatoxymelatonin (aMT6s) is a primary urinary metabolite of
      melatonin. We examined the association between aMT6s levels and shift work
      estimated by a job exposure matrix (JEM) among healthy participants of the
      Shanghai Women's Health Study. METHODS: Creatinine-adjusted aMT6s levels were
      measured in the urine samples of 300 women and related to JEM shift work
      categories. RESULTS: Adjusted geometric means of aMT6s levels from urine samples
      collected before 08:00 hours were lower among persons holding nighttime shift
      work jobs. The adjusted aMT6s levels (ng/mg creatinine) were 8.36 [95% confidence
      intervals (95% CI) 4.47-15.6], 6.37 (95% CI 3.53-11.5), 6.20 (95% CI 3.33-11.5),
      3.81 (95% CI 2.02-7.19), and 3.70 (95% CI 1.92-7.11) from the lowest (never held
      a shift work job) to the highest (current job likely involved all-night shift
      work) shift work JEM scores (P=0.05). CONCLUSION: Our results indicate that
      nightshift work JEM scores were significantly and inversely associated with aMT6s
      levels in early morning spot urine samples collected between 07:00-08:00 hours.

PMID- 22975885
TI  - Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in
      the critically ill.
AB  - OBJECTIVE: Given the importance of inflammation in acute kidney injury and the
      relationship between vitamin D and inflammation, we sought to elucidate the
      effect of vitamin D on acute kidney injury. We hypothesized that deficiency in 25
      hydroxyvitamin D prior to hospital admission would be associated with acute
      kidney injury in the critically ill. DESIGN: Two-center observational study of
      patients treated in medical and surgical intensive care units. SETTING: Two
      hundred nine medical and surgical intensive care beds in two teaching hospitals
      in Boston, Massachusetts. PATIENTS: Two thousand seventy-five patients, aged >=
      18 yrs, in whom serum 25-hydroxyvitamin D was measured prior to hospitalization
      between 1998 and 2009. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: The
      exposure of interest was preadmission serum 25-hydroxyvitamin D and categorized a
      priori as deficiency (25-hydroxyvitamin D <15 ng/mL), insufficiency (25
      hydroxyvitamin D 15-30 ng/mL), or sufficiency (25-hydroxyvitamin D >= 30 ng/mL).
      The primary outcome was acute kidney injury defined as meeting Risk, Injury,
      Failure, Loss, and End-stage kidney disease (RIFLE) Injury or Failure criteria.
      Logistic regression examined the RIFLE criteria outcome. Adjusted odds ratios
      were estimated by multivariate logistic regression models. Preadmission 25
      hydroxyvitamin D deficiency is predictive of acute kidney injury. Patients with
      25-hydroxyvitamin D deficiency have an odds ratio for acute kidney injury of 1.73
      (95% confidence interval 1.30-2.30; p < .0001) relative to patients with 25
      hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a
      significant predictor of acute kidney injury following multivariable adjustment
      (adjusted odds ratio 1.50; 95% confidence interval 1.42-2.24; p < .0001).
      Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for acute
      kidney injury of 1.49 (95% confidence interval 1.15-1.94; p = .003) and an
      adjusted odds ratio of 1.23 (95% confidence interval 1.12-1.72; p = .003)
      relative to patients with 25-hydroxyvitamin D sufficiency. In addition,
      preadmission 25-hydroxyvitamin D deficiency is predictive of mortality. Patients
      with 25-hydroxyvitamin D insufficiency have an odds ratio for 30-day mortality of
      1.60 (95% confidence interval 1.18-2.17; p = .003) and an adjusted odds ratio of
      1.61 (95% confidence interval 1.06-1.57; p = .004) relative to patients with 25
      hydroxyvitamin D sufficiency. CONCLUSION: Deficiency of 25-hydroxyvitamin D prior
      to hospital admission is a significant predictor of acute kidney injury and
      mortality in a critically ill patient population.

PMID- 22975886
TI  - Probiotics in the critically ill: a systematic review of the randomized trial
      evidence.
AB  - OBJECTIVE: Critical illness results in changes to the microbiology of the
      gastrointestinal tract, leading to a loss of commensal flora and an overgrowth of
      potentially pathogenic bacteria. Administering certain strains of live bacteria
      (probiotics) to critically ill patients may restore balance to the microbiota and
      have positive effects on immune function and gastrointestinal structure and
      function. The purpose of this systematic review was to evaluate the effect of
      probiotics in critically ill patients on clinical outcomes. DESIGN: Systematic
      review. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We searched
      computerized databases, reference lists of pertinent articles, and personal files
      from 1980 to 2011. We included randomized controlled trials enrolling critically
      ill adults, which evaluated probiotics compared to a placebo and reported
      clinically important outcomes (infections, mortality, and length of stay). A
      total of 23 randomized controlled trials met inclusion criteria. Probiotics were
      associated with reduced infectious complications as documented in 11 trials (risk
      ratio 0.82; 95% confidence interval 0.69-0.99; p = .03; test for heterogeneity p
      = .05; I 44%). When data from the seven trials reporting ventilator-associated
      pneumonia were pooled, ventilator-associated pneumonia rates were also
      significantly reduced with probiotics (risk ratio 0.75; 95% confidence interval
      0.59-0.97; p = .03; test for heterogeneity p = .16; I 35%). Probiotics were
      associated with a trend toward reduced intensive care unit mortality (risk ratio
      0.80; 95% confidence interval 0.59-1.09; p = .16; test for heterogeneity p = .89;
      I 0%) but did not influence hospital mortality. Probiotics had no effect on
      intensive care unit or hospital length of stay. Compared to trials of higher
      methodological quality, greater treatment effects were observed in trials of a
      lower methodological quality. CONCLUSIONS: Probiotics appear to reduce infectious
      complications including ventilator-associated pneumonia and may influence
      intensive care unit mortality. However, clinical and statistical heterogeneity
      and imprecise estimates preclude strong clinical recommendations. Further
      research on probiotics in the critically ill is warranted.

PMID- 22975887
TI  - The stress response and critical illness: a review.
AB  - OBJECTIVES: To describe different paradigms that define the stress response, and
      to postulate how stress is implicated in the pathophysiology of critical illness.
      DESIGN: Articles were identified through a search of PubMed and Google Scholar.
      RESULTS: The stress response represents a bundle of adaptive behavioral,
      physiological, and cellular responses. Although generally beneficial, an
      important adverse consequence of excessive stress is organ dysfunction. Many
      interventions currently applied to the critically ill patient are additive and
      may contribute to organ dysfunction, renewed deterioration, and impaired or
      delayed recovery. Resilience (rho) summarizes the interaction among
      predisposition factors, injury (or stressors), and the body's allostatic
      responses. Resilience changes over the course of critical illness but is
      potentially measurable and may be used to identify at-risk patients and to tailor
      therapy. CONCLUSION: Critical illness may represent a stress-related
      decompensation syndrome mediated by neural, endocrine, bioenergetic, and immune
      systems. As patients pass through the separate phases of critical illness,
      consideration should be given to different therapeutic end points. This may be
      particularly pertinent during the established organ dysfunction phase where
      targeting of normal values may have deleterious consequences. Improved strategies
      could thus emerge from an increased knowledge and monitoring of the stress
      response, and what constitutes an optimal adaptive state as it evolves in the
      course of critical illness.

PMID- 22975888
TI  - Respiratory toxicity of buprenorphine results from the blockage of P-glycoprotein
      mediated efflux of norbuprenorphine at the blood-brain barrier in mice.
AB  - OBJECTIVES: Deaths due to asphyxia as well as following acute poisoning with
      severe respiratory depression have been attributed to buprenorphine in opioid
      abusers. However, in human and animal studies, buprenorphine exhibited ceiling
      respiratory effects, whereas its metabolite, norbuprenorphine, was assessed as
      being a potent respiratory depressor in rodents. Recently, norbuprenorphine, in
      contrast to buprenorphine, was shown in vitro to be a substrate of human P
      glycoprotein, a drug-transporter involved in all steps of pharmacokinetics
      including transport at the blood-brain barrier. Our objectives were to assess P
      glycoprotein involvement in norbuprenorphine transport in vivo and study its role
      in the modulation of buprenorphine-related respiratory effects in mice. SETTING:
      University-affiliated research laboratory, INSERM U705, Paris, France. SUBJECTS:
      Wild-type and P-glycoprotein knockout female Friend virus B-type mice.
      INTERVENTIONS: Respiratory effects were studied using plethysmography and the P
      glycoprotein role at the blood-brain barrier using in situ brain perfusion.
      MEASUREMENTS AND MAIN RESULTS: Norbuprenorphine(>= 1 mg/kg) and to a lesser
      extent buprenorphine (>= 10 mg/kg) were responsible for dose-dependent
      respiratory depression combining increased inspiratory (TI) and expiratory times
      (TE). PSC833, a powerful P-glycoprotein inhibitor, significantly enhanced
      buprenorphine-related effects on TI (p < .01) and TE (p < .05) and
      norbuprenorphine-related effects on minute volume (VE, p < .05), TI, and TE (p <
      .001). In P-glycoprotein-knockout mice, buprenorphine-related effects on VE (p <
      .01), TE (p < .001), and TI (p < .05) and norbuprenorphine-related effects on VE
      (p < .05) and TI (p < .001) were significantly enhanced. Plasma norbuprenorphine
      concentrations were significantly increased in PSC833-treated mice (p < .001),
      supporting a P-glycoprotein role in norbuprenorphine pharmacokinetics. Brain
      norbuprenorphine efflux was significantly reduced in PSC833-treated and P
      glycoprotein-knockout mice (p < .001), supporting P-glycoprotein-mediated
      norbuprenorphine transport at the blood-brain barrier. CONCLUSIONS: P
      glycoprotein plays a key-protective role in buprenorphine-related respiratory
      effects, by allowing norbuprenorphine efflux at the blood-brain barrier. Our
      findings suggest a major role for drug-drug interactions that lead to P
      glycoprotein inhibition in buprenorphine-associated fatalities and respiratory
      depression.

PMID- 22975889
TI  - G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against
      spinal cord injury.
AB  - OBJECTIVE: What underlies the protection of estrogen against spinal cord injury
      remains largely unclear. Here, we investigated the expression pattern of a new
      estrogen receptor, G-protein coupled estrogen receptor 1 in the spinal cord and
      its role in estrogenic protection against spinal cord injury. DESIGN AND
      SETTINGS: Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest
      Hospital. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals
      subjected to spinal cord injury were divided into six groups and given vehicle
      solution, 17beta-estradiol, or G-protein coupled estrogen receptor 1 agonist G-1
      at 15 mins and 24 hrs postinjury, or given nuclear estrogen receptor antagonist
      ICI 182,780 at 1 hr before spinal cord injury followed by 17beta-estradiol
      administration at 15 mins and 24 hrs postinjury, or given G-protein coupled
      estrogen receptor 1 specific antisense or random control oligonucleotide at 4
      days before spinal cord injury followed by 17beta-estradiol administration at 15
      mins and 24 hrs postinjury. MEASUREMENTS: Male Sprague-Dawley rats were subjected
      to spinal cord injury using a weight-drop injury approach. Immunohistochemical
      assays were used to observe the distribution and cell-type expression pattern of
      G-protein coupled estrogen receptor 1. The terminal deoxynucleotidyl transferase
      dUTP nick-end labeling-staining assay and behavior tests were employed to assess
      the role of G-protein coupled estrogen receptor 1 in mediating estrogenic
      protection against spinal cord injury. MAIN RESULTS: We show that G-protein
      coupled estrogen receptor 1 is mainly distributed in the ventral horn and white
      matter of the spinal cord, which is totally different from nuclear estrogen
      receptors. We also show that G-protein coupled estrogen receptor 1 is
      specifically expressed by neurons, oligodendrocytes, and microglial cells, but
      not astrocytes. Furthermore, estrogen treatment prevents spinal cord injury
      induced apoptotic cell death and enhances functional recovery after spinal cord
      injury, which can be mimicked by the specific G-protein coupled estrogen receptor
      1 agonist G-1 and inhibited by specific knockdown of G-protein coupled estrogen
      receptor 1 expression, but not pure nuclear ER antagonist ICI 182,780. Finally,
      we show that estrogen or G-1 up-regulates the protein expression level of G
      protein coupled estrogen receptor 1 to intensify estrogenic effects during spinal
      cord injury. CONCLUSIONS: These results reveal that G-protein coupled estrogen
      receptor 1 may mediate estrogenic neuroprotection against spinal cord injury, and
      underline the promising potential of estrogen with its new target G-protein
      coupled estrogen receptor 1 for the treatment of spinal cord injury patients.

PMID- 22975891
TI  - Red blood cell transfusions are associated with lower mortality in patients with
      severe sepsis and septic shock: a propensity-matched analysis*.
AB  - OBJECTIVES: To evaluate the effects of transfusions in patients with severe
      sepsis and septic shock on mortality. DESIGN: Propensity-matched analysis of a
      prospective observational database (April 2005 to February 2009). SETTING: Twenty
      two medical and surgical intensive care units in 12 teaching hospitals in Korea.
      PATIENTS: One thousand fifty-four patients with community-acquired severe sepsis
      and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the
      1,054 patients, 407 (38.6%) received a blood transfusion. The mean pretransfusion
      hemoglobin level was 7.7 +/- 1.2 g/dL. Transfused patients had higher 28-day and
      in-hospital mortality rates (32.7% vs. 17.3%; p < .001, 41.3% vs. 20.3%; p <
      .001, respectively) and a longer duration of hospital stay (21 [interquartile
      range, 10-35] vs. 13 [interquartile range, 8-24] days; p < .001), but were more
      severely ill at admission (lower systolic blood pressure, higher Acute Physiology
      and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment
      score at admission). In 152 pairs matched according to the propensity score
      depending on patient transfusion status, transfused patients had a lower risk of
      7-day (9.2% vs. 27.0%; p < .001), 28-day (24.3% vs. 38.8%; p = .007), and in
      hospital mortality rates (31.6% vs. 42.8%; p = .044). After adjusting for blood
      transfusion as a time-dependent variable in multivariable analysis, blood
      transfusion was independently associated with lower risk of 7-day (hazard ratio
      0.42, 95% confidence interval 0.19-0.50, p = .026), 28-day (hazard ratio 0.43,
      95% confidence interval 0.29-0.62, p < .001), and in-hospital mortality (hazard
      ratio 0.51, 95% confidence interval 0.39-0.69, p < .001). CONCLUSIONS: In this
      observational study of patients with community-acquired severe sepsis and septic
      shock, red blood cell transfusions were associated with lower risk of mortality.

PMID- 22975892
TI  - Undergraduate medical education in critical care.
AB  - OBJECTIVE: To review the current status of critical care education of medical
      students, focusing on how early, vigorous undergraduate training may address the
      needs of the learners and society. DATA SOURCES: Literature review of focused
      PubMed searches, online databases, and reference lists of recent publications.
      RESULTS: Although management of unstable and critically ill patients is required
      of most interns, undergraduate education in these skills remains largely
      elective, scattered, and highly variable. Critical care competencies for medical
      school graduates have not been established in the United States, and many
      students feel unprepared for these responsibilities that they assume as interns.
      Several successful approaches to medical student education in critical care have
      been demonstrated, and the availability of simulation technology provides new
      educational opportunities. Early exposure to other medical disciplines has
      influenced medical student career choice, although this has not been studied in
      regards to critical care fields. CONCLUSIONS: Undergraduate medical education in
      critical care would be advanced by consolidation and organization into formal
      curricula. These would teach biomedical and humanistic skills essential to
      critical care but valuable in all medical settings. Early, well-planned exposure
      to critical care as a distinct discipline might increase student interest in
      careers in the field. The effects of educational interventions on the acquisition
      of knowledge, attitudes, and skills as well as long-term career choice should be
      subjected to rigorous study.

PMID- 22975890
TI  - Effectiveness of a multidimensional approach for prevention of ventilator
      associated pneumonia in adult intensive care units from 14 developing countries
      of four continents: findings of the International Nosocomial Infection Control
      Consortium.
AB  - OBJECTIVES: The aim of this study was to analyze the effect of the International
      Nosocomial Infection Control Consortium's multidimensional approach on the
      reduction of ventilator-associated pneumonia in patients hospitalized in
      intensive care units. DESIGN: A prospective active surveillance before-after
      study. The study was divided into two phases. During phase 1, the infection
      control team at each intensive care unit conducted active prospective
      surveillance of ventilator-associated pneumonia by applying the definitions of
      the Centers for Disease Control and Prevention National Health Safety Network,
      and the methodology of International Nosocomial Infection Control Consortium.
      During phase 2, the multidimensional approach for ventilator-associated pneumonia
      was implemented at each intensive care unit, in addition to the active
      surveillance. SETTING: Forty-four adult intensive care units in 38 hospitals,
      members of the International Nosocomial Infection Control Consortium, from 31
      cities of the following 14 developing countries: Argentina, Brazil, China,
      Colombia, Costa Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, Panama,
      Peru, and Turkey. PATIENTS: A total of 55,507 adult patients admitted to 44
      intensive care units in 38 hospitals. INTERVENTIONS: The International Nosocomial
      Infection Control Consortium ventilator-associated pneumonia multidimensional
      approach included the following measures: 1) bundle of infection-control
      interventions; 2) education; 3) outcome surveillance; 4) process surveillance; 5)
      feedback of ventilator-associated pneumonia rates; and 6) performance feedback of
      infection-control practices. MEASUREMENTS: The ventilator-associated pneumonia
      rates obtained in phase 1 were compared with the rates obtained in phase 2. We
      performed a time-series analysis to analyze the impact of our intervention. MAIN
      RESULT: During phase 1, we recorded 10,292 mechanical ventilator days, and during
      phase 2, with the implementation of the multidimensional approach, we recorded
      127,374 mechanical ventilator days. The rate of ventilator-associated pneumonia
      was 22.0 per 1,000 mechanical ventilator days during phase 1, and 17.2 per 1,000
      mechanical ventilator days during phase 2.The adjusted model of linear trend
      shows a 55.83% reduction in the rate of ventilator-associated pneumonia at the
      end of the study period; that is, the ventilator-associated pneumonia rate was
      55.83% lower than it was at the beginning of the study. CONCLUSION: The
      implementation the International Nosocomial Infection Control Consortium
      multidimensional approach for ventilator-associated pneumonia was associated with
      a significant reduction in the ventilator-associated pneumonia rate in the adult
      intensive care units setting of developing countries.

PMID- 22975893
TI  - Does glyphosate impact on Cu uptake by, and toxicity to, the earthworm Eisenia
      fetida?
AB  - Glyphosate (GPS) is a wildly-used pesticide throughout the world. It affects
      metal behaviors in soil-water system as its functional groups such as amine,
      carboxylate and phosphonate can react with metal ions to form metal complexes.
      The reaction will result in the decreasing of heavy metal bioavailability. A
      laboratory experiment was conducted to investigate the interactions between GPS
      and copper (Cu) on the acute toxicity of soil invertebrate earthworm (Eisenia
      fetida), which was exposed to aqueous solutions for 48 h with different mixing
      concentrations of Cu and GPS (technical-grade Gly acid). The mortality rates, Cu
      uptake by earthworm, and some biomarkers such as superoxide dismutase (SOD)
      activity, glutathione (GSH) content, and acetylcholinesterase (AchE) activity
      were measured. The mortality rates and whole-worm metal burdens increased
      significantly with the increasing Cu concentration in solution. However, toxicity
      of GPS to earthworms was not observed in this study. Furthermore, the presence of
      GPS could significantly reduce the acute toxicity of Cu to earthworms. The
      mortality rates decreased sharply and the uptake of Cu was nearly halted in the
      presence of GPS. In addition, the SOD activity, GSH content, and AchE activity
      almost declined to the levels of the control. These results demonstrate that GPS
      could control the toxicity as well as the bioavailability of heavy metals in soil
      solutions where both GPS and heavy metals often coexist.

PMID- 22975894
TI  - Multiple environmental stressors elicit complex interactive effects in the
      western fence lizard (Sceloporus occidentalis).
AB  - Evaluation of multiple-stressor effects stemming from habitat degradation,
      climate change, and exposure to chemical contaminants is crucial for addressing
      challenges to ecological and environmental health. To assess the effects of
      multiple stressors in an understudied taxon, the western fence lizard (Sceloporus
      occidentalis) was used to characterize the individual and combined effects of
      food limitation, exposure to the munitions constituent 2,4,6-trinitrotoluene
      (TNT), and Plasmodium mexicanum (lizard malaria) infection. Three experimental
      assays were conducted including: Experiment I--TNT * Food Limitation, Experiment
      II--Food Limitation * Malaria Infection, and Experiment III--TNT * Malaria
      Infection. All experiments had a 30 day duration, the malaria treatment included
      infected and non infected control lizards, food limitation treatments included an
      ad libitum control and at least one reduced food ration and TNT exposures
      consisting of daily oral doses of corn oil control or a corn oil-TNT suspension
      at 5, 10, 20, 40 mg/kg/day. The individual stressors caused a variety of effects
      including: reduced feeding, reduced testes mass, anemia, increased white blood
      cell (WBC) concentrations and increased mass of liver, kidney and spleen in TNT
      exposures; reduced cholesterol, WBC concentrations and whole body, testes and
      inguinal fat weights given food limitation; and increased WBC concentrations and
      spleen weights as well as decreased cholesterol and testes mass in malaria
      infected lizards. Additive and interactive effects were found among certain
      stressor combinations including elimination of TNT-induced hormesis for growth
      under food limitation. Ultimately, our study indicates the potential for effects
      modulation when environmental stressors are combined.

PMID- 22975895
TI  - Esfenvalerate toxicity to the cladoceran Ceriodaphnia dubia in the presence of
      green algae, Pseudokirchneriella subcapitata.
AB  - The presence of phytoplankton, like other particulate organic matter, can
      interfere with the effects of hydrophobic contaminants such as pyrethroid
      pesticides. However, the reduction or elimination of toxicity by algae added as
      food during testing is not taken into account in standard US EPA whole effluent
      toxicity (WET) zooplankton tests. On the other hand, WET test conditions may
      overestimate toxicity of such compounds in highly productive surface waters with
      high concentrations of detritus and other particulate matter. In addition, WET
      tests do not measure impaired swimming ability or predator avoidance behavior as
      an indicator of increased mortality risk. This study used a modified version of
      the US EPA WET Ceriodaphnia dubia acute test to investigate the effects of
      phytoplankton on toxicity of the pyrethroid insecticide, esfenvalerate. Animals
      were exposed simultaneously to different concentrations of esfenvalerate and
      green algae (Pseudokirchneriella subcapitata). Mortality and predation risk were
      recorded after 4 and 24 h. Algae at or below concentrations specified in the WET
      protocol significantly reduced mortality. Regardless, organisms exposed to
      esfenvalerate were unable to avoid simulated predation in the presence of algae
      at any concentration. After 12 h, esfenvalerate adsorbed to algae represented 68
      99 % of the total amount recovered. The proportion of algae-bound insecticide
      increased with algal concentration indicating that conclusions drawn from
      toxicity tests in which algae are added as food must be interpreted with caution
      as the dissolved fraction of such hydrophobic contaminants is reduced.
      Additionally, our results strongly suggest that the EPA should consider adding
      ecologically-relevant endpoints such as swimming behavior to standard WET
      protocols.

PMID- 22975897
TI  - Attitudes toward psychological telehealth: current and future clinical
      psychologists' opinions of internet-based interventions.
AB  - OBJECTIVES: The current study explored differences in acceptance of telehealth
      interventions amongst currently licensed and future clinicians with a focus on
      web camera-based intervention. The influence of theoretical orientation was also
      assessed. METHOD: An online survey assessed 717 participants comprising 409
      licensed psychologists (40.8% female, mean age = 56.57, standard deviation [SD] =
      11.01) and 308 doctoral-level students (78.9% female, mean age = 27.66, SD = 5.9)
      across domains of endorsement and rejection. RESULTS: Binary logistic regression
      indicated no significant difference between currently licensed and future
      psychologists in their endorsement of telehealth modalities. Cognitive
      behavioral, cognitive, behavioral, and systems psychologists were significantly
      more accepting of telehealth interventions than were dynamic/analytic or
      existential therapists. CONCLUSIONS: Increasing exposure to telehealth through
      education as well as continued research on efficacy for specific diagnoses may
      help psychologists to more effectively determine whether telehealth is the "best
      fit" for both clinician and client.

PMID- 22975896
TI  - Evidence for multisensory integration in the elicitation of prior entry by
      bimodal cues.
AB  - This study reports an experiment investigating the relative effects of
      intramodal, crossmodal and bimodal cues on visual and auditory temporal order
      judgements. Pairs of visual or auditory targets, separated by varying stimulus
      onset asynchronies, were presented to either side of a central fixation (+/-45
      degrees ), and participants were asked to identify the target that had occurred
      first. In some of the trials, one of the targets was preceded by a short, non
      predictive visual, auditory or audiovisual cue stimulus. The cue and target
      stimuli were presented at the exact same locations in space. The point of
      subjective simultaneity revealed a consistent spatiotemporal bias towards targets
      at the cued location. For the visual targets, the intramodal cue elicited the
      largest, and the crossmodal cue the smallest, bias. The bias elicited by the
      bimodal cue fell between the intramodal and crossmodal cue biases, with
      significant differences between all cue types. The pattern for the auditory
      targets was similar apart from a scaling factor and greater variance, so the
      differences between the cue conditions did not reach significance. These results
      provide evidence for multisensory integration in exogenous attentional cueing.
      The magnitude of the bimodal cueing effect was equivalent to the average of the
      facilitation elicited by the intramodal and crossmodal cues. Under the assumption
      that the visual and auditory cues were equally informative, this is consistent
      with the notion that exogenous attention, like perception, integrates multimodal
      information in an optimal way.

PMID- 22975898
TI  - A nonparametric test for Markovianity in the illness-death model.
AB  - Multistate models are useful tools for modeling disease progression when survival
      is the main outcome, but several intermediate events of interest are observed
      during the follow-up time. The illness-death model is a special multistate model
      with important applications in the biomedical literature. It provides a suitable
      representation of the individual's history when a unique intermediate event can
      be experienced before the main event of interest. Nonparametric estimation of
      transition probabilities in this and other multistate models is usually performed
      through the Aalen-Johansen estimator under a Markov assumption. The Markov
      assumption claims that given the present state, the future evolution of the
      illness is independent of the states previously visited and the transition times
      among them. However, this assumption fails in some applications, leading to
      inconsistent estimates. In this paper, we provide a new approach for testing
      Markovianity in the illness-death model. The new method is based on measuring the
      future-past association along time. This results in a detailed inspection of the
      process, which often reveals a non-Markovian behavior with different trends in
      the association measure. A test of significance for zero future-past association
      at each time point is introduced, and a significance trace is proposed
      accordingly. Besides, we propose a global test for Markovianity based on a
      supremum-type test statistic. The finite sample performance of the test is
      investigated through simulations. We illustrate the new method through the
      analysis of two biomedical data analysis.

PMID- 22975899
TI  - Conservative surgery, external radiotherapy, and HDR brachytherapy in a single
      fraction of 7 Gy in early breast cancer: long-term toxicity and esthetic
      assessment.
AB  - INTRODUCTION: The essential issue in conservative treatment is the quality in
      breast preservation. When risk factors for local relapse exist, a tumour bed
      boost is required, but the boost choice remains controversial. Prospectively, we
      studied long-term toxicity, cosmetic outcome and prognostic factors. MATERIALS
      AND METHODS: After conservative treatment, 115 patients received a single dose of
      7 Gy HDR-brachytherapy (HDR-BT) boost between June 1996 and December 2005. Late
      toxicity was assessed using the LENT-SOMA scale. For esthetic assessment, a
      subjective scale was used for patients and a modified Fehlauer scale for
      physicians. Mean age was 56.6 years. Invasive ductal carcinoma (78 %) and
      lumpectomy (60 %) were predominantly reported. 48 % received chemotherapy (CT).
      RESULTS: Regarding toxicity, 39 % of patients reported breast pain, 75 %
      fibrosis, 56 % telangiectasias, 19 % lymphoedema, and 51 % retraction/atrophy.
      Concerning management, 22 % of patients with pain and 45 % with lymphoedema were
      treated. The esthetic result was found satisfactory by 96 % of the patients and
      85 % of the physicians. Fibrosis was influenced by CT and a larger irradiated
      volume and telangiectasias by a greater implant volume. CONCLUSIONS: HDR-BT boost
      shows good cosmetic effects with acceptable toxicity. Patients overestimate the
      esthetic outcome. LENT/SOMA is useful to assess chronic toxicity.

PMID- 22975900
TI  - Dose-volume histogram parameters for predicting radiation pneumonitis using
      receiver operating characteristic curve.
AB  - OBJECTIVE: To assess the predictability of dose-volume histogram (DVH) parameters
      for radiation pneumonitis (RP) using receiver operating characteristic (ROC)
      curve. METHODS: One hundred and thirty-five cases of locally advanced non-small
      cell lung cancer patients treated with three-dimensional radiotherapy and
      chemotherapy were analyzed retrospectively. The end point of follow-up was >=2
      grade RP defined according to the National Cancer Institute Common Terminology
      Criteria for Adverse Events, version 3.0. The ROC curve was used to explore the
      predictive sensitivity (SEN), specificity (SPE), positive predictive value (PPV),
      and negative predictive value (NPV) for potential DVH parameters associated with
      RP. RESULTS: Relative volumes of total lungs receiving >=5 Gy (V(5)), >=10 Gy
      (V(10)), >=13 Gy (V(13)), >=20 Gy (V(20)), and mean lung dose (MLD), were all
      correlated to the development of RP (p < 0.05), among which V 5 and V 20 were the
      most important factors (p = 0.045 and 0.037; OR = 3.166 and 3.030). However,
      collinearity was found between V(5) and V(20) (Spearman's rho 0.771, p < 0.01).
      The area under the ROC curve was 0.643 and 0.648 for using V(5) and V(20) as
      predictors. If predictive cut-off values were established as follows: V(5) = 0.8
      and V(20) = 0.3, the parameters could provide predictive SEN, SPE, PPV and NPV
      were 0.387 and 0.581, 0.882 and 0.701, 0.444 and 0.321, and 0.855 and 0.873,
      respectively. CONCLUSIONS: V(5) and V(20) could act as predictors for RP;
      however, single DVH metrics did not appear to have high predictive power for RP.

PMID- 22975901
TI  - Clinical report on transarterial neoadjuvant chemotherapy of malignant fibrous
      histiocytoma in soft tissue.
AB  - PURPOSE: To review the experience in transarterial neoadjuvant chemotherapy of
      malignant fibrous histiocytoma (MFH) in soft tissue and to analyze the factors
      related to prognosis of MFH in soft tissue. METHODS: Between September 1999 and
      December 2011, 101 cases of MFH in soft tissue patients treated by transarterial
      administration of Cisplatin, Adriamycin and Norcantharidin were divided into
      primary group and recurrent group, and the clinical documents were reviewed. Nine
      factors that might affect prognosis such as age, sex, tumor size, tumor site,
      tumor infiltration depth, recurrence if any, pathological type, histologic grade
      and histologic response of chemotherapy were analyzed statistically. RESULTS: The
      5-year relapse-free survival rate and the overall survival rate were 70.5 and
      75.0 %, respectively, in the primary group; 56.1 and 57.9 %, respectively, in the
      recurrent group. Univariate analysis (log-rank test) showed that the factors
      affecting the prognosis were age (P = 0.03), tumor size (P = 0.01), pelvic tumor
      (P = 0.02), recurrence if any (P = 0.004), histologic grade (P = 0.01), and
      histologic response to chemotherapy (P = 0.007). Multivariate analysis showed
      that the major factors affecting prognosis were pelvic tumor (P = 0.01), tumor
      size (P = 0.002), histologic grade (P = 0.002), recurrence if any (P = 0.0004),
      and histologic response to chemotherapy (P = 0.008). CONCLUSION: Transarterial
      neoadjuvant chemotherapy can significantly increase the curative efficacy of
      chemotherapy and survival rate in MFH treatment.

PMID- 22975902
TI  - Cochlear implantation assisted by noninvasive image guidance.
AB  - OBJECTIVE: We recently developed a new noninvasive registration method for image
      guided otologic surgery (STAMP method). We investigated the benefit and potential
      drawback of our new method in clinical application and tested the feasibility of
      routine image-guided surgery. STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral university hospital. PATIENTS: Forty-six cases (45 patients)
      that underwent cochlear implantation in Kyushu University Hospital during the
      period of 2007 and 2010 were informed of the option to use navigated surgery.
      INTERVENTION: Twenty-five cochlear implantations were performed using STAMP
      registered image-guided surgery. MAIN OUTCOME MEASURE: The error of image-guided
      surgery and time of surgery were collected and analyzed. RESULTS: STAMP method
      offered serviceable accuracy in 18/25 cochlear implantations. The learning curve
      suggested that the accuracy is at least stabilizing, if not improving, and the
      success rate is expected to rise. Time of cochlear implant surgery was not
      significantly extended by the use of image guidance. CONCLUSION: STAMP method had
      comparable errors with minimal invasiveness. Our new method potentially enables
      routine use of image-guided surgery.

PMID- 22975903
TI  - Pediatric cochlear implants:  additional disabilities prevalence, risk factors,
      and effect on language outcomes.
AB  - OBJECTIVE: To determine the prevalence of additional disabilities in a pediatric
      cochlear population, to identify medical and radiologic conditions associated
      with additional disabilities, and to identify the effect of additional
      disabilities on speech perception and language at 12 months postoperatively.
      STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center and
      cochlear implant program. PATIENTS: Records were reviewed for children 0 to 16
      years old inclusive, who had cochlear implant-related operations over a 12-month
      period. INTERVENTIONS: Diagnostic and rehabilitative. MAIN OUTCOME MEASURES:
      Additional disabilities prevalence; medical history and radiologic abnormalities;
      and the effect on Categories of Auditory Performance (CAP) score at 12 months
      postoperatively. RESULTS: Eighty-eight children having 96 operations were
      identified. The overall prevalence of additional disabilities (including
      developmental delay, cerebral palsy, visual impairment, autism and attention
      deficit disorder) was 33%. The main conditions associated with additional
      disabilities were syndromes and chromosomal abnormalities (87%), jaundice (86%),
      prematurity (62%), cytomegalovirus (60%), and inner ear abnormalities including
      cochlea nerve hypoplasia or aplasia (75%) and semicircular canal anomalies (56%).
      At 12 months postoperatively, almost all (96%) of the children without additional
      disabilities had a CAP score of 5 or greater (speech), compared with 52% of
      children with additional disabilities. Children with developmental delay had a
      median CAP score of 4, at 12 months compared with 6 for those without
      developmental delay. CONCLUSION: Additional disabilities are prevalent in
      approximately a third of pediatric cochlear implant patients. Additional
      disabilities significantly affect the outcomes of cochlear implants.

PMID- 22975904
TI  - Position of TORP on the stapes footplate assessed with cone beam computed
      tomography.
AB  - OBJECTIVE: To improve hearing outcomes of ossiculoplasty with a total ossicular
      replacement prosthesis (TORP) in ears lacking a footplate superstructure, 3
      dimensional computed tomography (3D CT) images were reconstructed to verify the
      position of the TORP on the footplate and contact between the TORP and the stapes
      footplate. STUDY DESIGN: Retrospective study. SETTING: University-affiliated
      tertiary referral center. PATIENTS: Six ears of 6 patients who underwent
      ossiculoplasty with TORP and were followed for greater than 3 years
      postoperatively. INTERVENTION: Cone beam CT (CBCT) images. MAIN OUTCOME MEASURES:
      An en face view of the stapes footplate and a volume-rendered 3D image were
      reconstructed. RESULTS: The en face view of the stapes footplate showed whether
      the TORP was centered on the stapes footplate. Volume-rendered 3D CBCT images
      revealed TORP malpositioning or migration, which were not detected on 2
      dimensional CBCT images. In such cases, the TORP shaft was in contact with the
      wall of the oval window niche or the TORP had moved from the stapes footplate.
      CONCLUSION: Accurate visualization of TORP location on the footplate is
      important. Images that accurately show the position of the TORP on the stapes
      footplate will help improve hearing outcomes.

PMID- 22975905
TI  - Clinical use of vestibular evoked myogenic potentials in the evaluation of
      patients with air-bone gaps.
AB  - OBJECTIVE: To determine the value of vestibular evoked myogenic potential (VEMP)
      test in clinical evaluation of air-bone gaps. STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: A total of 120 patients
      underwent VEMP testing during clinical investigation of significant air-bone gaps
      in their audiograms. INTERVENTION(S): Otologic examination and surgeries, high
      resolution computerized tomography (CT), air and bone audiometry, tympanometry,
      acoustic reflex, and VEMP test. MAIN OUTCOME MEASURE(S): Imaging studies
      demonstrating structural anomalies in the temporal bone. Audiologic outcomes of
      air-bone gaps and VEMP thresholds. Surgical findings confirming imaging results.
      RESULTS: Middle ear pathologies, such as otosclerosis and chronic otitis media,
      were identified in 50 patients, and all of them had absent VEMP responses
      elicited by air-conduction stimuli. Moreover, 13 of them had successful middle
      ear surgeries with closures of the air-bone gaps. Abnormally low VEMP thresholds
      were found in 71 of 73 ears with inner ear anomalies, such as semicircular canal
      dehiscence and enlarged vestibular aqueduct. Seven patients with superior
      semicircular canal dehiscence underwent plugging procedure via middle fossa
      approach, and VEMP thresholds became normalized after the surgery in 3 of them.
      VEMP test failed to provide accurate diagnosis in only 3 cases. CONCLUSION: Air
      bone gaps may be a result of various otologic pathologies, and the VEMP test is
      useful during clinical evaluation, better than tympanometry and acoustic
      reflexes. To avoid unnecessary middle ear surgery for air-bone gaps with unknown
      or unsure cause, VEMP test should be used in the differential diagnosis before an
      expensive imaging study.

PMID- 22975906
TI  - Herpes simplex meningitis after removal of a vestibular schwannoma:  case report
      and review of the literature.
AB  - OBJECTIVE: We present a case of postoperative herpes simplex type 1 viral
      meningitis after retrosigmoid craniotomy and uncomplicated removal of a
      vestibular schwannoma. This is a very rare complication that can mimic aseptic
      meningitis and could lead to devastating consequences for the patient, if
      unrecognized. PATIENT: A healthy 49-year-old woman underwent retrosigmoid
      craniotomy and resection of a 2.4-cm vestibular schwannoma. She developed
      worsening headache and low-grade fever on postoperative Day 10 and underwent
      lumbar puncture showing a lymphocyte predominant pleocytosis. Polymerase chain
      reaction was positive for herpes simplex type 1 virus; bacterial cultures were
      negative. The patient subsequently developed a pseudomeningocele and mild
      hydrocephalus. INTERVENTION: The patient was readmitted to the hospital, started
      on corticosteroids, and a lumbar drain was placed. She completed a 14-day course
      of antiviral therapy (4 d intravenous as an inpatient and 10 d oral outpatient
      therapy). RESULTS: At 1 month follow-up, she was completely asymptomatic, and her
      pseudomeningocele had resolved. CONCLUSION: The diagnosis of herpes simplex viral
      meningitis should be suspected in clinical cases of postsurgical meningitis with
      a lymphocyte predominant pleocytosis and negative bacterial cultures. Antiviral
      therapy should be initiated immediately after confirmatory polymerase chain
      reaction testing to avoid potential long-term sequelae of a herpes simplex
      infection of the central nervous system.

PMID- 22975907
TI  - Collision tumor of the facial nerve:  a synchronous seventh nerve schwannoma and
      neurofibroma.
AB  - OBJECTIVE: To report a novel case of a collision tumor involving an intraparotid
      neurofibroma and a mastoid segment facial nerve schwannoma. STUDY DESIGN:
      Clinical capsule report. SETTING: Tertiary academic referral center. PATIENT: A
      29-year-old woman with a 2-year history of an asymptomatic enlarging left
      infraauricular mass and normal FN function presented to a tertiary care referral
      center. Computed tomography and magnetic resonance imaging demonstrated a cystic
      lesion in the deep portion of the parotid gland extending into the stylomastoid
      foramen. INTERVENTION: The patient underwent superficial parotidectomy, and a
      cystic parotid mass was found to be intrinsic to the intraparotid facial nerve. A
      portion of the mass was biopsied, and intraoperative frozen section pathology was
      consistent with a neurofibroma. A mastoidectomy with FN decompression was then
      performed until a normal-appearing segment was identified just proximal to the
      second genu. After biopsy, proximal facial nerve stimulation failed to elicit
      evoked motor potentials, and en bloc resection was performed. RESULTS: Final
      pathology demonstrated a schwannoma involving the mastoid segment and a
      neurofibroma involving the proximal intraparotid facial nerve. CONCLUSION: We
      report the first case of a facial nerve collision tumor involving an intraparotid
      neurofibroma and a mastoid segment facial nerve schwannoma. Benign FN sheath
      tumors of the parotid gland are rare but should be considered in the differential
      diagnosis of a parotid mass.

PMID- 22975908
TI  - Histologic characterization of human ear ossicles for the development of tissue
      engineered replacements.
AB  - HYPOTHESIS: Precise knowledge of the expression and distribution of extracellular
      matrix (ECM) molecules and osteochondrogenic markers helps target the proper in
      vitro regeneration of novel ossicular chain (OC) replacements via tissue
      engineering (TE). BACKGROUND: We performed an extensive histologic analysis of
      human ear ossicles in healthy adults. A variety of OC prostheses are currently
      available, but extrusion of synthetic devices still represents an important
      clinical phenomenon. TE is a novel discipline combining stem cells, bioresorbable
      biomaterials, and stimulatory factors for the development of new living tissues
      in vitro, which might offer forefront opportunities to otologic surgery. However,
      to drive stem cell differentiation correctly, the final tissue target must be
      accurately known. METHODS: Malleus, incus, and stapes were collected from
      cadaveric temporal bones. TE PORPs were obtained via osteodifferentiation of
      human mesenchymal stromal cells on polymeric scaffolds. Histochemical and
      immunohistochemical analyses were performed to detect ECM molecules and
      osteochondrogenic markers. RESULTS: Malleus and incus showed the same histologic
      tissue type, with similar levels of expression and distributions for both ECM
      molecules and osteochondrogenic markers, whereas the stapes showed self-standing
      histologic patterns. In TE PORPs, mesenchymal ECM synthesis and early stage
      development of ossification sites could be observed, highlighting good cellular
      integration with the scaffold biomaterial. CONCLUSION: Detailed morphologic study
      of the ossicles provides data related to tissue dynamics involved in their
      development, defining features of tissue differentiation and maturation. Such
      findings underpin the future development of biomimetic ossicular replacement,
      data that can guide tissue-engineered ossiculoplasty.

PMID- 22975909
TI  - Magnetic-force quartz crystal microbalance for the detection of chemical
      interactions.
AB  - The magnetic-force quartz crystal microbalance (QCM) method was attempted for the
      dynamic evaluation of chemical interactions.  Thiol-modified magnetic particles
      bound to a QCM gold electrode of less than three layers were pulled by a magnetic
      force, and the dissociation dynamics of the magnetic particles was measured based
      on the change in the weight as a function of time under different temperatures. 
      From an analysis of the dissociated layers and the activation energy for the
      dissociation, the chemical interactions between particles were evaluated.

PMID- 22975910
TI  - Advances in silver ion chromatography for the analysis of fatty acids and
      triacylglycerols-2001 to 2011.
AB  - An effort is made to critically present the achievements in silver ion
      chromatography during the last decade. Novelties in columns, mobile-phase
      compositions and detectors are described. Recent applications of silver ion
      chromatography in the analysis of fatty acids and triacylglycerols are presented
      while stressing novel analytical strategies or new objects. The tendencies in the
      application of the method in complementary ways with reversed-phase
      chromatography, chiral chromatography and, especially, mass detection are
      outlined.

PMID- 22975911
TI  - Recent progress and applications of ion-exclusion/ion-exchange chromatography for
      simultaneous determination of inorganic anions and cations.
AB  - One of the ultimate goals of ion chromatography is to determine both anions and
      cations found in samples with a single chromatographic run.  In the present
      article, recent progress in ion-exclusion/ion-exchange chromatography for the
      simultaneous determinations of inorganic anions and cations are reviewed. 
      Firstly, the principle and the control for the simultaneous separation and
      detection of analyte ions using ion-exclusion/cation-exchange chromatography with
      a weakly acidic cation-exchange column are outlined.  Then, advanced
      chromatographic techniques in terms of analytical time, selectively and
      sensitivity are summarized.  As a related method, ion-exclusion/anion-exchange
      chromatography with an anion-exchange column could be used for the simultaneous
      determination of inorganic nitrogen species, such as ammonium, nitrite and
      nitrate ions.  Their usefulness and applications to water-quality monitoring and
      related techniques are also described.

PMID- 22975912
TI  - Development of an electric charge-tunable micro-column for capillary liquid
      chromatography.
AB  - An electric charge-tunable micro-column (CTMC) was developed as a precolumn for
      reversed-phase capillary chromatography using conductive carbon fibers as the
      stationary phase.  The carbon fibers, which constitute one electrode, are packed
      into a heat-shrinkable tube, which is attached to a stainless-steel column body. 
      The mobile phase flows into CTMC through a stainless-steel tube that acts as a
      counter electrode.  The retention times for hydrophobic and ionic compounds are
      controlled by the applied potential.  The characteristics, such as the
      electrolysis efficiency and shift in retention factor, were evaluated.  As a case
      study, estrogens in spiked beef were analyzed by capillary chromatography.  With
      no applied potential, the resolution between the unknown peak and estriol and the
      recoveries of estriol were 0.81 and 65.5%, respectively.  These values improved
      to 1.2 and 78.8%, respectively, upon applying +500 mV.  These results indicate
      that a high-resolution capillary chromatography system can be achieved with CTMC.

PMID- 22975913
TI  - Improved detection sensitivity and selectivity attained by open-sandwich
      selection of an anti-estradiol antibody.
AB  - The development of a rapid and specific assay for 17beta-estradiol (E2) will
      accelerate its in vitro diagnostics and/or environmental pollution control. Here,
      we employed an open-sandwich (OS) selection scheme to improve the sensitivity for
      E2 in an OS immunoassay, which is based on antigen-dependent stabilization of the
      antibody (Ab) variable region, Fv, where the two domains (V(H) and V(L))
      dissociated in the absence of an antigen. The V(H) domain of a cloned anti-E2
      antibody displayed on M13 phage was randomly mutated, and after three OS
      biopanning rounds, a mutant that showed higher sensitivity in OS-ELISA for E2 was
      identified. Interestingly, compared with the wild-type V(H), the cross-reactivity
      of the mutant was significantly decreased for the analogous steroid testosterone,
      both in OS and competitive ELISAs. This is the first report concerning selection
      for an anti-hapten Ab without using any hapten-carrier conjugates, and the method
      will be especially suitable for selecting Ab fragments that show better
      performance in hapten OS immunoassays.

PMID- 22975914
TI  - Elimination of influence by interference substance on amperometric enzyme
      biosensor response using wavelet transformation.
AB  - Wavelet transformation was applied as an elimination method of influence by an
      interfering substance on an amperometric biosensor. The current responses of a bi
      enzyme type lactose biosensor in a solution containing both lactose and ascorbic
      acid were analyzed by wavelet transformation. The power spectrum density for
      ascorbic acid was detected selectively at around 0.125 Hz. The current component
      due to ascorbic acid was eliminated at 98% from the current response of the
      biosensor by wavelet transformation.

PMID- 22975915
TI  - CMOS image sensor-based immunodetection by refractive-index change.
AB  - A complementary metal oxide semiconductor (CMOS) image sensor is an intriguing
      technology for the development of a novel biosensor. Indeed, the CMOS image
      sensor mechanism concerning the detection of the antigen-antibody (Ag-Ab)
      interaction at the nanoscale has been ambiguous so far. To understand the
      mechanism, more extensive research has been necessary to achieve point-of-care
      diagnostic devices. This research has demonstrated a CMOS image sensor-based
      analysis of cardiovascular disease markers, such as C-reactive protein (CRP) and
      troponin I, Ag-Ab interactions on indium nanoparticle (InNP) substrates by simple
      photon count variation. The developed sensor is feasible to detect proteins even
      at a fg/mL concentration under ordinary room light. Possible mechanisms, such as
      dielectric constant and refractive-index changes, have been studied and proposed.
      A dramatic change in the refractive index after protein adsorption on an InNP
      substrate was observed to be a predominant factor involved in CMOS image sensor
      based immunoassay.

PMID- 22975916
TI  - Sensitive and selective label-free alkaline phosphatase detection based on DNA
      hairpin probe.
AB  - Here, we present a label-free, simple and signal-on architecture for fluorescent
      alkaline phosphatase (ALP) biosensor utilizing an SYBR Green I (SG) assisted
      fluorescence amplification method. The strategy relies on the fact that ALP
      provides a significant barrier to lambda exonuclease (lambda exo) activity by a
      dephosphorylating DNA hairpin probe (HP), and SG shows a considerable
      fluorescence intensity enhancement upon binding to double-stranded DNA (dsDNA)
      than single-stranded DNA (ssDNA). Our method is simple, sensitive and selective,
      which can also successfully detect the activity of ALP in complex biological
      fluids. The results have revealed that the method allows a specific and
      quantitative assay of the target ALP with a wide linear response range from 0.4
      to 200 U/mL and a detection limit of 0.05 U/mL.

PMID- 22975917
TI  - Amino-functionalized nano-size composite materials for dispersive solid-phase
      extraction of phosphate in water samples.
AB  - An efficient analytical method for the preconcentration and determination of
      phosphate in water samples at trace levels was proposed.  The method was based on
      sample enrichment using dispersive solid-phase extraction (dSPE) with
      tetraethylenepentamine (TEPA)-functionalized nano-size composite materials (TEPA
      NCMs) as sorbents, which were fully characterized.  Various parameters affecting
      the extraction efficiency were systematically investigated.  After extraction,
      the post-adsorbed TEPA-NCMs were eluted by a NaOH solution for desorption of the
      phosphate.  The resulting eluate containing phosphate was determined by a
      spectrophotometric method.  The limit of detection (LOD) and the limit of
      quantification (LOQ) were 0.29 and 0.96 MUg L(-1), respectively.  The relative
      standard deviations (RSDs) were lower than 8.0% with average recoveries ranging
      from 91 to 118%.  The present method was successfully applied to the
      determination of phosphate at trace levels in real water samples, and it was
      confirmed that the TEPA-NCMs are highly effective dSPE materials.

PMID- 22975919
TI  - Matrix-assisted laser desorption ionization mass spectrometry of maltohexaose and
      acetylsalicylic acid using alkali metal cation-substituted zeolites.
AB  - Using alkali-metal cation-substituted zeolites and 2,4,6-trihydroxyacetophenone
      (THAP), which is a typical organic matrix molecule for matrix-assisted laser
      desorption ionization (MALDI), mass spectrometry has been performed for
      maltohexaose and acetylsalicylic acid, and the cation-selective ionization of
      these analytes was achieved. It is found that a complex of cation-substituted
      zeolite and THAP can be applicable to a compound that is hard to be ionized by a
      proton adduction in conventional MALDI.

PMID- 22975918
TI  - Human serum albumin-modified Fe3O4 magnetic nanoparticles for affinity-SALDI-MS
      of small-molecule drugs in biological liquids.
AB  - Here, we report on the use of human serum albumin (HSA)-modified Fe(3)O(4)
      nanoparticles (NPs) (HSA-Fe(3)O(4) NPs) for affinity-SALDI-MS of small drugs in
      human biological liquids. We demonstrated that HSA-Fe(3)O(4) NPs effectively
      captured small drugs from human urine and serum via the interactions between HSA
      and these drugs. The drugs adsorbed on HSA could then be identified by directly
      introducing the HSA-Fe(3)O(4) NPs into a mass spectrometer for SALDI-MS analysis.
      The ability of HSA to interact with multiple small drugs facilitated the
      simultaneous detection of a 4-drug-mixture in serum, viz., phenytoin, ibuprofen,
      camptothecin, and warfarin sodium, by affinity-SALDI-MS using HSA-Fe(3)O(4) NPs.
      In contrast, matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) with an organic matrix could detect only warfarin sodium. We also
      demonstrated the capacity of affinity-SALDI-MS to quantify warfarin sodium in
      urine samples across a range of 50 - 1000 MUM (R(2) = 0.998) when using HSA
      Fe(3)O(4) NPs. The detection sensitivity was further improved to a range of 5 -
      100 MUM (R(2) = 0.999) by using denatured HSA. The open structure of denatured
      HSA may enhance the effective extraction of small drugs from biological liquids,
      and increase the detection-sensitivity of affinity-SALDI-MS. Affinity-SALDI-MS
      using protein-modified Fe(3)O(4) NPs can open up new approaches to the analytical
      detection of small drugs in biological liquids by SALDI-MS.

PMID- 22975920
TI  - High-throughput screening of transglutaminase activity using plasmonic
      fluorescent nanocomposites.
AB  - We describe a high-throughput screening (HTS) assay for transglutaminase (TG)
      enzyme activity using plasmonic fluorescent nanocomposites. We used TG to
      covalently crosslink 500 MUM solution of 5'-biotinamidopentylamine (BP) to N,N'
      dimethylcasein (DMC) which was adsorbed onto 384-well microplates. We then bound
      0.2 - 2.0 * 10(11)/mL of 10 nm gold nanoparticles-streptavidin conjugate (10 nm
      AuNPs-SA) to BP via biotin-streptavidin interactions. Finally, J-aggregation of
      cyanine 1 (25 MUM) or 2 (10 MUM) upon the 10 nm AuNPs elicited absorption and
      fluorescence signaling of TG catalysis. The cyanines could be added sequentially
      to elicit green (590 nm) and red (700 nm) spectral responses from the same set of
      reactions. Catalysis was linear (r(2) > 0.98) up to 10 min within a linear
      dynamic range (LDR) of 0.1 - 5 MUg/mL enzyme. The multi-wavelength interrogation
      offered fast results (< 5 min), sensitivity (limit of detection, LOD of 5 ng or
      64 fmol TG) and intermediate precision (relative standard deviation, RSD of < 20%
      over 42 days). Plasmonic fluorescent nanocomposites offer new ways of
      interrogating biomolecules in HTS format.

PMID- 22975921
TI  - Current status of homogeneity and stability of the reference materials for
      nutrients in seawater.
AB  - The development of Reference Materials for Nutrients in Seawater (RMNS) has been
      in progress since 1993.  When RMNS were produced for nitrate, silicate, and
      phosphate, their initial homogeneities were as low as 0.1 to 0.2% in samples of
      high-nutrient seawater, such as deep water from the Pacific Ocean.  The relative
      standard uncertainties associated with instability during long-term (4.8 years)
      storage were approximately 0.2, 0.2, and 0.4% for nitrate, silicate, and
      phosphate, respectively.  No instability was observed for 1.9 to 6.4 years based
      on the ISO Guide 35:2006 criteria; however, the relative standard uncertainties
      associated with instability during long-term storage were larger than the initial
      homogeneities of RMNS.  RMNS produced by state-of-the-art techniques are
      currently available for global use to improve the comparability of nutrients data
      in the open ocean and, as discussed here, are reliable candidates to be used for
      certified reference materials.

PMID- 22975922
TI  - Determination of monomer conversion in methacrylate-based polymer monoliths fixed
      in a capillary column by pyrolysis-gas chromatography.
AB  - Monomer conversion and the resultant copolymer composition of polymer monolith
      columns are important factors for controlling column characteristics.  We propose
      a new method to determine monomer conversion to a polymer monolith fixed in a
      capillary column using pyrolysis-gas chromatography.  Small pieces of a
      poly(butyl methacrylate-co-ethylene dimethacrylate (BMA-co-EDMA)) monolith column
      were pyrolyzed at 450 degrees C with poly(ethyl methacrylate) as a non-volatile
      internal standard.  The monomer conversions were estimated from the corresponding
      relative peak intensities in the pyrogram.  It was determined that the conversion
      of EDMA was significantly greater than that of BMA in a low-conversion UV
      polymerized poly(BMA-co-EDMA) monolithic capillary column.

PMID- 22975923
TI  - Investigations into tie lines and solubility curves on phase diagrams in open
      tubular capillary chromatography using ternary mixed-carrier solvents.
AB  - Open-tubular capillary chromatography using a ternary solvent mixture consisting
      of a water-hydrophilic-hydrophobic organic solvent as a carrier solution has been
      developed.  When the ternary carrier solution is fed into the capillary tube, the
      carrier solvents are radially distributed and generate inner and outer phases in
      the tube.  The outer phase functions as a pseudo-stationary phase in
      chromatography.  In this study, investigations proceeded with reference to the
      tie lines and solubility curves on the phase diagram of the ternary mixed
      solvents.  Model analytes, 1-naphthol and 2,6-naphthalenedisulfonic acid, were
      separated in this order with ternary water-acetonitrile-ethyl acetate solvent
      mixtures (organic solvent-rich solutions) that possessed various solvent
      compositions on the tie lines.  In addition, fluorescence photographs of the dyes
      dissolved in the ternary solvents in the capillary tubes were observed with a
      fluorescence microscope-CCD camera system.  It was found that the separation
      performance on the chromatograms and the phase formation observed in the
      fluorescence photographs were related to data provided through the tie lines and
      solubility curves on the phase diagram.  The solvent compositions on the same tie
      line that gave different volume ratios of upper and lower phases in a vessel
      influenced the chromatographic separation, or the resolutions of the analytes,
      and also the inner and outer phase formation in the chromatography.

PMID- 22975924
TI  - Synthesis of superhydrophobic silica nanofibrous membranes with robust thermal
      stability and flexibility via in situ polymerization.
AB  - Superhydrophobic silica nanofibrous membranes exhibiting robust thermal stability
      and flexibility were prepared by a facile combination of electrospun silica
      nanofibers and a novel in situ polymerized fluorinated polybenzoxazine (F-PBZ)
      functional layer that incorporated SiO(2) nanoparticles (SiO(2) NPs). By using F
      PBZ/SiO(2) NP modification, the pristine hydrophilic silica nanofibrous membranes
      were endowed with superhydrophobicity with a water contact angle (WCA) of up to
      161 degrees . Surface morphological studies have revealed that the wettability of
      resultant membranes could be manipulated by tuning the surface composition as
      well as the hierarchical structures. Quantitative fractal dimension analysis
      using the N(2) adsorption method has confirmed the correlation between
      hierarchical roughness and WCA for the modified membranes. Furthermore, the as
      prepared membranes exhibited high thermal stability (450  degrees C), good
      flexibility (0.0127 gf cm), and comparable tensile strength (2.58 MPa),
      suggesting their use as promising materials for a variety of potential
      applications in high-temperature filtration, self-cleaning coatings, catalyst
      carriers, etc., and also provided new insight into the design and development of
      functional nanofibrous membranes through F-PBZ modification.

PMID- 22975925
TI  - Pain and other symptoms and their relationship to quality of life in cancer
      patients on opioids.
AB  - PURPOSE: The purpose of this study was to assess pain, other symptoms and QOL,
      and the relationship between these variables, among cancer patients on strong
      opioids. METHODS: The study was cross-sectional, descriptive, and correlational.
      A convenience sample of 150 cancer patients, >=18 years, all on strong opioids
      for >= 3 days was recruited. RESULTS: The mean (SD) age was 64.7 (12.7) years,
      and 59 % were women. Mean (SD) time from cancer diagnosis was 36.3 (55.1) months.
      The median number of symptoms was 9, range 1-16 and the mean (SD) severity was
      1.9 (0.5) on a 1-4 scale. Pain was one of the most prevalent (90 %) and severe
      symptoms with a mean (SD) of 2.56 (0.9). Number of symptoms explained 25.8 % of
      the variance in QOL, adjusted for age and sex. Another model, also adjusted for
      age and sex, showed that pain, fatigue, insomnia and depression, explained 33.6 %
      of the variance in QOL. CONCLUSIONS: The symptomatology in this study was similar
      to studies on patients with advanced cancer. QOL was associated with the number
      of symptoms patients experience and individual symptoms, notably fatigue and
      pain. Despite the use of strong opioids, pain was both common and severe,
      suggesting under-treatment. Pain and other symptoms need to be assessed and
      managed in order to improve patients' QOL. Special attention needs to be paid to
      multisymptom management in patients on opioids.

PMID- 22975927
TI  - Phosphorescent, liquid-crystalline complexes of platinum(II): influence of the
      beta-diketonate co-ligand on mesomorphism and emission properties.
AB  - Two series of rod-like ortho-platinated complexes bound to a range of beta
      diketonate co-ligands are reported of the form [Pt(N^C)(O^O)]. The liquid crystal
      and luminescent properties are influenced through the introduction of different
      beta-diketonates (O^O) as well as through the presence of a fused cyclopentene
      ring on the N^C-coordinated 2-phenylpyridine ligand. For metal complexes, smectic
      phases are dominant but no mesomorphism is exhibited when the beta-diketonate is
      hexafluorinated acetylacetonate (1,1,1-5,5,5-hexafluoro-2,4-pentandione). The
      introduction of an unsymmetrical trifluoroacetyl acetonate (1,1,1-trifluoro-2,4
      pentandione) ligand is particularly interesting due to the discovery of the beta
      diketonate as a dynamic system that readily isomerises to a 1:1 ratio under
      thermal conditions, from an initial ratio of 3:1 formed during the synthesis. As
      expected, the presence of the 3,5-heptanedionato co-ligand decreases the
      transition temperatures due to the introduction of a larger lateral substituent.
      Unfortunately complexes based on 2-phenylpyridine ligands with a fused
      cyclopentene ring are, with one exception, not mesomorphic. With the exception of
      the hexafluoroacetyl acetonate complexes, the materials are brightly luminescent
      and have excited state lifetimes between 13 and 30 MUs with emission quantum
      efficiencies exceeding 0.5, with one as high as 0.7. A time-dependent density
      functional theory (TD-DFT) study suggests that the lack of emission from the
      hexafluoroacetyl acetonate complexes may be associated with large structural
      distortion upon formation of the excited state, as well as to poorer overlap of
      orbitals leading to a lower radiative rate constant. The same analysis provides
      an explanation for the apparently quite different emission efficiencies of the
      two isomers of the trifluoroacetyl acetonate complexes.

PMID- 22975926
TI  - What is the use? Application of the short form (SF) questionnaires for the
      evaluation of treatment effects.
AB  - BACKGROUND: Health status has evolved as a clinical outcome measure that is of
      great interest in medical care. However, there is still debate about the
      appropriateness of scoring algorithms for the often used short form
      questionnaires. Therefore, our aim was to evaluate the consequences of the
      traditional scoring procedure based on orthogonal factor rotation for clinical
      applications by (a) re-evaluating the results of randomized controlled trials
      (RCTs) on the effectiveness of antidepressants in improving health status in
      cardiac patients and (b) comparing empirical evidence on depression and health
      status using orthogonal and oblique factor rotation (alternative scoring method)
      in a community sample and a heart failure (HF) sample. METHODS: This is a
      systematic literature review and cross-sectional analysis among 1,598 community
      sample participants and 282 HF patients. RESULTS: Orthogonal rotation
      artificially forces the mental component summary (MCS) and physical component
      summary (PCS) to be unrelated, which is illustrated in two of the three included
      RCTs. Two RCTs showed improvements in MCS, but no improvement in PCS over time.
      Cross-sectional analysis in the two datasets showed that employing the
      alternative scoring algorithm resulted in higher negative correlations of MCS and
      PCS with depression, and a gradual decline in MCS with each decile of decline in
      PCS. CONCLUSION: Our data showed that appropriate carefulness is needed when
      calculating and interpreting summary scores. The traditional scoring algorithm
      seems inappropriate to objectively evaluate the effects of interventions on both
      the MCS and the PCS. Awareness in the design and evaluation of interventions
      using these outcomes is warranted.

PMID- 22975928
TI  - Parkinson's disease medication use and costs following deep brain stimulation.
AB  - The costs of treating Parkinson's disease (PD) are significant. Medication
      reductions usually occur following deep brain stimulation (DBS), but less is
      known about the relative costs of DBS targets, the globus pallidum (GPi) or the
      subthalamic nucleus (STN). This article reports medication costs between best
      medical therapy (BMT) and DBS over 6 months postintervention and by DBS target
      over 36 months postsurgery. Prescription use and costs for patients (n = 161)
      with advanced PD from a multisite randomized trial of BMT and DBS were examined
      overall and by drug category. Medication adjustment occurred at the discretion of
      the neurologists. PD medications were extracted from the Department of Veterans
      Affairs Decision Support System database. Levodopa equivalents (LEDD) were
      significantly lower for DBS than for BMT patients at 6 months (1101 vs 1398 mg; P
      = .005), but costs were similar (US$1750 vs US$1589; P = .55). LEDD decreased
      following GPi and STN DBS (1395-1161 mg, P = .014; and 1347-891 mg, P < .0001,
      respectively) in the first 6 months, but was lower for STN than for GPi over 36
      months following DBS (P = .03). Total PD medication costs per 6-month intervals
      decreased over 36 months (P < .0001), but did not differ by target (P = .50) in
      the mixed-model analysis. However, cumulative medication costs over 36 months
      were lower for the STN than for GPi patients. PD medication use and costs
      decreased following DBS in either target over 36 months, but cumulative costs
      were less for STN than for GPi.

PMID- 22975929
TI  - [Study of transportation and localization of cell surface proteins in
      Porphyromoans gingivalis].

PMID- 22975932
TI  - Erythrocyte aggregation: basic aspects and clinical importance.
AB  - Red blood cell (RBC) aggregate to form two- and three-dimensional structures when
      suspended in aqueous solutions containing large plasma proteins or polymers; this
      aggregation is reversible and shear dependent (i.e., dispersed at high shear and
      reformed at low or stasis). The extent of aggregation is the main determinant of
      low shear blood viscosity, thus predicting an inverse relationship between
      aggregation and in vivo blood flow. However, the effects of aggregation on
      hemodynamic mechanisms (e.g., plasma skimming, Fahraeus Effect, microvascular
      hematocrit) may promote rather than impede vascular blood flow. The impact of
      enhanced RBC aggregation on endothelial function and hemostatic mechanisms adds
      further complexity, thereby requiring specific attention to the nature, extent
      and time course of aggregation when considering its overall influence on tissue
      perfusion. A detailed understanding of aggregation effects is important from a
      clinical point of view since it may be enhanced during a variety of
      pathophysiological processes, including infections, circulatory and metabolic
      disorders, hematological pathologies and several other disease states. Altered
      RBC aggregation may be an indicator of disease as well as a factor affecting the
      course of the clinical condition; the prognostic value of RBC aggregation indices
      has been demonstrated in various diseases. Currently, RBC aggregation is an
      easily and accurately measurable parameter, and therefore may be expected to have
      broader clinical usage in the future.

PMID- 22975933
TI  - Microcirculation diagnostics and applied studies in circulatory shock - research
      from the bench to the bedside.
AB  - Macrohemodynamic targets such as mean arterial pressure, cardiac output, and
      mixed or central venous oxygen saturation have been used to guide treatment of
      patients presenting circulatory shock. However, it has been shown that despite of
      improvement of macrocirculatory parameters there is persisting microcirculatory
      dysfunction. The restoration of microvascular perfusion in order to improve
      oxygenation, prevent tissue hypoxia, and maintain organ function represents the
      main aim of hemodynamic resuscitation. Therefore, microcirculatory targets may
      represent the most important endpoints to optimize therapy of circulatory shock.

PMID- 22975930
TI  - An investigation of the antidepressant action of xiaoyaosan in rats using ultra
      performance liquid chromatography-mass spectrometry combined with metabonomics.
AB  - A rapid, highly sensitive, and selective method was applied in a non-invasive way
      to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra
      performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics.
      Many significantly altered metabolites were used to explain the mechanism.
      Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs
      with a relatively clear mechanism of action to evaluate the efficiency and to
      predict the mechanism of action of XYS. Urine obtained from rats subjected to
      chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct
      changes in the pattern of metabolites in the rat urine after CUMS production and
      drug intervention were observed using partial least squares-discriminant
      analysis. The results of behavioral tests and multivariate analysis showed that
      CUMS was successfully reproduced, and a moderate-dose XYS produced significant
      therapeutic effects in the rodent model, equivalent to those of the positive
      control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant
      changes induced by CUMS were identified, and 17 biomarker candidates for stress
      and drug intervention were identified. The therapeutic effect of XYS on
      depression may involve regulation of the dysfunctions of energy metabolism, amino
      acid metabolism, and gut microflora changes. Metabonomic methods are valuable
      tools for measuring efficacy and mechanisms of action in the study of traditional
      Chinese medicines.

PMID- 22975934
TI  - Progress in vascular graft substitute.

PMID- 22975935
TI  - High resolution ultrasound including elastography and contrast-enhanced
      ultrasound (CEUS) for early detection and characterization of liver lesions in
      the humanized tumor mouse model.
AB  - PURPOSE: In this study we investigated the sensitivity of high resolution
      ultrasound (HRU) in the detection of small liver tumors and its microcirculation
      in a humanized tumor mouse model (HTM). These mice develop a complete human
      immune system and human breast cancer growth in the liver which allows the
      investigation of antibody based immunotherapies under human like conditions.
      METHOD: HTM were generated by the co-transplantation of human breast cancer cells
      and human hematopoietic stem cells. HRU, Doppler sonography (CCDS), contrast
      enhanced ultrasound (CEUS) and color-coded elastography were performed on all HTM
      and confirmed by histopathological assessment. RESULTS: Using HRU and CEUS,
      noncystic solid liver lesions between 2 and 11 mm (mean 3.5 mm) size were
      detectable in HTM. Granulomatous areas were identified by B-scan imaging, showing
      areas of higher stiffness in elastography and areas without contrast media uptake
      in the late phase (CEUS). In addition, CEUS detected capillary microcirculation
      of benign and malignant liver lesions smaller than 10 mm. CONCLUSION: Beyond
      human breast cancer HTM additionally developed small parenchymal liver lesions,
      which could be characterized by HRU in combination with CEUS and elastography in
      vivo. Nevertheless, the defined diagnoses of solid liver lesions less than 5 mm
      require confirmation by histopathology.

PMID- 22975936
TI  - Impact of antibiotics on the microcirculation in local and systemic inflammation.
AB  - The main function of antibiotics is related to their capacity to eliminate a
      microorganism. In addition to the antimicrobial function of antibiotics, they are
      known to have anti-inflammatory and vasomodulatory effects on the
      microcirculation. The ability of non-antimicrobial derivatives of antibiotics to
      control inflammation illustrates the distinct anti-microbial and anti
      inflammatory roles of antibiotics. In this review, we discuss the impact of
      antibiotics on leukocyte recruitment and the state of the microcirculation.
      Literature reporting the effect of antibiotics in non-infectious inflammatory
      conditions is reviewed as well as the studies demonstrating the anti-inflammatory
      effects of antibiotics in animal models of infection. In addition, the effect of
      the antibiotics on the immune system is summarized in this review, in order to
      postulate some mechanisms of action for the proand anti-inflammatory contribution
      of antibiotics. Literature reported the effect of antibiotics on the production
      of cytokines, chemotaxis and recruitment of leukocytes, production of reactive
      oxygen species, process of phagocytosis and autophagy, and apoptosis of
      leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory
      effect on the microcirculation. Thus, we suggest a model for spectrum of anti
      inflammatory and vasomodulatory effects of antibiotics in the microcirculation of
      animals in local and systemic inflammation. Although the literature suggests the
      ability of antibiotics to modulate leukocyte recruitment and microperfusion, the
      process and the mechanism of action are not fully characterized. Studying this
      process will expand the knowledge base that is required for the selection of
      antibiotic treatment based on its anti-inflammatory functions, which might be
      particularly important for critically ill patients.

PMID- 22975937
TI  - Detection of microvascularization of thyroid carcinomas using linear high
      resolution contrast-enhanced ultrasonography (CEUS).
AB  - BACKGROUND: Preoperative differentiation of thyroid nodules in benign and
      malignant pathologies still represents an unsolved problem in endocrinology. In
      the presented study, contrast-enhanced ultrasonography (CEUS) was applied as a
      new diagnostic tool detecting the microvascularisation of thyroid carcinomas.
      METHODS: 167 patients underwent surgery for suspicious thyroid nodules between
      05/2011 and 08/2012. Contrast-enhanced ultrasonography (CEUS) with a linear probe
      (6-9 MHz, LOGIQE9/GE), color coded Doppler sonography (CCDS) and Power Doppler
      ultrasonography (PD) were performed in all patients preoperatively. Removed
      nodules were proved by histology. In case of carcinoma morphological
      characteristics and especially microvascularization were analyzed using time
      intensity curves (TIC) in selected regions of interest (ROI). RESULTS: In total,
      22 thyroid carcinomas could be identified by histology. Using CEUS thyroid
      carcinomas in 19 patients showed early and irregular arterial vascularization
      followed by early arterial central wash-out. CCDS/PD, however, revealed irregular
      peripheral vascularization with low flow only in 8 cases. Further analysis
      resulted in a significant higher area under the curve (AUC) at the edge than in
      the tumor center but in a similar time to peak (TTP) in both regions.
      CONCLUSIONS: CEUS represents a highly sensitive method for the detection of the
      microvascularization of thyroid carcinomas. Future studies should compare these
      findings to benign pathologies in order to establish CEUS as a standard
      diagnostic procedure in the preoperative evaluation of suspicious thyroid
      nodules.

PMID- 22975938
TI  - Influence of radiographic contrast media (Iodixanol and Iomeprol) on the
      endothelin-1 release from human arterial and venous endothelial cells cultured on
      an extracellular matrix.
AB  - Various radiographic contrast media (RCM) are available for visualization of
      blood vessels in interventional cardiology which can vary widely in their
      physicochemical properties thereby influencing different functions of blood
      cells. In the in vitro study described here the influence of two RCMs on arterial
      as well as on venous endothelial cells was compared to control cultures and
      examined under statical culture conditions, thus eliminating the influence of RCM
      viscosity almost completely. The supplementation of the culture medium with RCM
      (30% v/v) resulted in clearly different reactions of the endothelial cells
      exposed. Exposition to Iodixanol supplemented culture medium was followed by
      endothelin-1 release from venous endothelial cells which was equivalent to the
      endothelin-1 release from venous control cultures. Compared to control cultures,
      venous endothelial cells exposed to culture medium supplemented with Iomeprol
      displayed a completely different reaction, the increase in endothelin-1 secretion
      was missing completely after a 12 hours exposure. Following a 12 hours exposure
      to both RCMs there were no longer endothelial cells adherent, neither in venous
      nor in arterial endothelial cell cultures. The study showed that not the wall
      shear stress was responsible for the differing effects visible after 1.5 min, 5
      min, and 12 hours exposure to culture media supplemented with RCM but differences
      in chemotoxicity of the RCM applied.

PMID- 22975939
TI  - High resolution contrast-enhanced ultrasound and 3-tesla dynamic contrast
      enhanced magnetic resonance imaging for the preoperative characterization of
      cervical lymph nodes: First results.
AB  - The reliable detection of cervical lymph node (LN) metastases is the planning
      basis of a selective neck dissection for patients with oral squamous cell
      carcinoma (OSCC). The aim of this study was to evaluate whether contrast-enhanced
      ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) together are able to improve the preoperative characterisation of LNs. A
      time intensity curve analysis has been performed using CEUS and DCE-MRI for ten
      LNs, where one LN has been examined per patient. The studied LNs consist of five
      with and five without metastases. In CEUS the mean time to peak (TTP) was 18 s
      (range 13-29 s, standard deviation (SD) +/- 7 s) for benign and 12 s (range 9-16
      s, SD +/- 4 s) for malignant LNs. In DCE-MRI the mean TTP was 27 s (range 18-36
      s, SD +/- 9 s) for benign and 21 s (range 18-27 s, SD +/- 5 s) for malignant LNs.
      Moreover, the relative signal change with respect to reference tissue was
      significantly higher for LNs with than for those without metastases in both CEUS
      and DCE-MRI. A combination of imaging morphology, CEUS and DCE-MRI might be a
      promising method for a reliable differentiation of benign and malignant LNs.

PMID- 22975940
TI  - First results of endocavity evaluation of the microvascularization of malignant
      prostate tumors using contrast enhanced ultrasound (CEUS) including perfusion
      analysis: first results.
AB  - AIM: Detection of prostate cancer lesions using transrectal contrast enhanced
      ultrasound (CEUS) of the prostate utilizing quantitative perfusion analysis.
      METHOD: 20 patients (mean age 63 years, 47-71) with biopsy proven prostate cancer
      underwent transrectal ultrasound (TRUS) prior to radical prostatectomy by 2
      experienced examiners using a multifrequency endocavitary probe (5-9 MHZ, LOGIQ
      E9, GE Healthcare, Chalfont St Giles, UK) to detect cancer-suspect lesions. CEUS
      was performed dynamically up to 3 Min after bolus injections of 2.4 ml SonoVue(r)
      (BRACCO, Italy). Digital cine loops were analyzed by an independent blinded
      examiner using perfusion quantification software with colour-coded parametric
      images in order to define suspect regions based on the perfusion-related
      parameters early wash in rate (WIR), mean transit time (MTT) and rise time (RT).
      The results of CEUS perfusion analysis were compared with the histopathology
      after surgery, obtained from whole mount sections. RESULTS: After prostatectomy
      and histopathology, 34 prostate cancer foci were found in 20 patients. In 30/34
      cases an early enhancement within the tumor was detected by CEUS perfusion
      analysis without early wash out. By evaluating the MTT and RT tumor detection was
      possible in 29/34 and 25/34 cases. The highest detection rate of prostate cancers
      was obtained by analysis of early contrast enhancement (priot to the normal
      prostate parenchyma), with a sensitivity of 88%, specificity 100%, NPP 60%, PPV
      90%, in clinically suspicious cases with good correlation to the postoperative
      histopathological findings (r = 0.728). CONCLUSION: This pilot study
      demonstrates, that quantitaive analysis of perfusion parameters obtained with
      transrectal CEUS could be helpful for characterization of neoplastic
      microcirculation of prostate cancer, for preoperative localization of cancer
      suspect areas and for therapy guidance and management.

PMID- 22975941
TI  - Cutaneous and muscular microcirculation in patients with terminal heart failure
      awaiting transplantation.
AB  - Heart failure patients are clinically characterized by extreme cardiomegaly,
      breathlessness, fluid retention and an early onset of fatigue. Studies have shown
      generalized restricted blood flow in those patients. Furthermore animal
      experiments proved an impaired blood flow and a diminished oxygen supply of the
      skeletal muscle in animals with chronic heart failure. Patients with chronic
      heart failure are limited to the extent of their ability to regulate their
      arterial pressure, especially in physical activity. It is however unclear in what
      way restriction of blood flow in the main arteries correlates with those in
      capillaries and to what extent. In this study it was examined the depth of
      capillary circulatory restriction as well as the disregulation of oxygen partial
      pressure in skeletal muscle in rest and stress conditions, in patients with
      terminal heart failure.

PMID- 22975942
TI  - Endothelial function and hemorheological parameters modulate coronary blood flow
      in patients without significant coronary artery disease.
AB  - BACKGROUND: Coronary (micro)vascular resistance is regulated by the complex
      interplay of several factors. Two potentially important determinants include
      endothelial function and the rheological properties of blood. However, their
      impact on the control of the coronary resistance vasculature is poorly
      understood. METHODS: The corrected Thrombolysis In Myocardial Infarction frame
      count (TIMIfc, an index of coronary flow velocity), conduit artery endothelial
      function, intima-media thickness of the common carotid artery and complete blood
      counts were measured in 145 patients undergoing elective coronary angiography.
      Patients with obstructive coronary artery disease or systemic conditions thought
      to be associated with microvascular disease were excluded from the analysis.
      RESULTS: There was a strong correlation between the TIMIfc measured in the three
      main coronary artery distributions (R values between 0.71 and 0.85, P < 0.00001).
      The TIMIfc was higher in males (P < 0.05), but there was no association with
      traditional risk factors for coronary artery disease (all P > 0.1). There was a
      correlation between TIMIfc and L-FMC, a parameter of resting endothelial function
      (R = 0.33, P < 0.0005). TIMIfc also correlated with mean platelet volume (a
      marker of platelet activation, R = 0.33, P < 0.001), and hematocrit (R = 0.33, P
      = 0.0002). There was no correlation between TIMIfc and carotid intima-media
      thickness and the degree of coronary atherosclerosis. Logistic regression
      analysis showed that L-FMC and hemorheological variables may explain as much as
      19% of the variability in TIMIfc. CONCLUSIONS: Resting peripheral endothelial
      function, as well as parameters of platelet function, correlate with coronary
      TIMIfc. These data emphasize the existence of an association between endothelial
      function, hemorheological variables and coronary blood flow velocity.

PMID- 22975943
TI  - Automated image-based analysis of adherent thrombocytes on polymer surfaces.
AB  - A dataset of 439 confocal laser scanning microscopic images was analyzed to
      investigate the potential of an image-based automated analysis for identifying
      and assessing adherent thrombocytes on polymer surfaces. Parameters for image
      optimization of glutardialdehyde induced fluorescence images were classified and
      data mining was performed using the Java image processing software ImageJ.
      Previously reported analysis required that each thrombocyte had to be identified
      interactively and outlined manually. Now, we were able to determine the number
      and area of adherent thrombocytes with high accuracy (spearman correlation
      coefficient r = 0.98 and r = 0.99) using a two-stage filter-set, including a
      rolling ball background subtraction- and a watershed segmentation-algorithm.
      Furthermore, we could proof a significant correlation between these parameters
      (spearman correlation coefficient r = 0.97), determining both as suitable
      predictors for the evaluation of material induced thrombogenicity. The here
      reported image-based automated analysis can be successfully applied to identify
      and measure adherent thrombocytes on polymer surfaces and, thus, might be
      successfully integrated in a high-throughput screening process to evaluate
      biomaterial hemocompatibility.

PMID- 22975944
TI  - Smooth muscle and endothelial cell behaviour on degradable
      copolyetheresterurethane films.
AB  - Stent thrombosis and restenosis after drug-eluting stent (DES) implantation
      remains a relevant problem in the cardiovascular field. The polymer-based
      biomaterial (e.g. stent coating) requirements are comprehensive, since the
      polymeric material ideally should ensure an effective re-endothelialization by
      recruiting endothelial cells (EC) and endothelial progenitor cells (EPC).
      Simultaneously, the polymer should effectively prevent adherence of smooth muscle
      cells (SMC) and thereby inhibiting restenosis. The aim of this study was to gain
      a basic understanding on the interaction of SMC and human umbilical vein
      endothelial cells (HUVEC) with nonporous polymer films. A multifunctional
      copolyetheresterurethane (PDC) was chosen as candidate material: PDC consists of
      poly(p-dioxanone) (PPDO) and poly(epsilon-caprolactone)-segments (PCL). In our
      study it was compared to the degradable PPDO homopolymer and poly(vinylidene
      fluoride-co-hexafluoropropene) (PVDF), an established coating material of DES in
      clinical applications intended for longterm applications. The films were analyzed
      according to their thermomechanical and surface properties before being examined
      in contact with HUVEC and SMC concerning cell viability, proliferation and
      adhesion. Experimental results showed that adhesion could be improved for HUVEC
      on PDC compared to PPDO and PVDF. In contrast, SMC attachment is largely
      suppressed on PDC polymeric films indicating a cell-specific response of HUVEC
      towards PDC. In conclusion, PDC represents a promising candidate material for
      future cardiovascular applications like e.g. biodegradable (PDC) stent coatings.

PMID- 22975945
TI  - Elastic multiblock copolymers for vascular regeneration: protein adsorption and
      hemocompatibility.
AB  - Hemocompatibility of elastic multiblock copolymers PDC, based on poly(p
      dioxanone) (PPDO)/poly(epsilon-caprolactone)-segments, capable of a shape-memory
      effect, and PDD, based on PPDO/poly((adipinate-alt-1,4-butanediol)-co-(adipinate
      alt-ethylene glycol)-co-adipinate-alt-diethylene glycol)-segments, was studied in
      order to assess their suitability for an application aiming at blood vessels
      regeneration. The results were compared with polypropylene (PP) which is a widely
      used blood-contacting material for devices as blood oxygenators and dialysis
      tubes. Protein adsorption studies showed diverse blood plasma proteins in a
      relatively high amount on both elastic polymers compared to the poor amount of
      plasma proteins adsorbed on PP. Study of the coagulation system revealed high
      thrombin formation on PDC and no difference in plasma kallikrein activation
      between elastic multiblock copolymers and the reference PP. Activation of
      complement system was higher for PDC followed by PDD and lower for PP. However,
      platelet adhesion and activation were hardly suppressed on the multiblock
      copolymers compared to the PP surface, where the number of adhered platelets and
      the activation rate were significant. The present results reveal that the tested
      multiblock copolymers with improved elastic properties and shape-memory
      capability (PDC) show low thrombogenicity and are promising candidates for
      vascular tissue engineering.

PMID- 22975946
TI  - Influence of fiber orientation in electrospun polymer scaffolds on viability,
      adhesion and differentiation of articular chondrocytes.
AB  - Degradable polymers with a tailorable degradation rate might be promising
      candidate materials for biomaterial-based cartilage repair. In view of the poor
      intrinsic healing capability of cartilage, implantation of autologous
      chondrocytes seeded on a biocompatible slow degrading polymer might be an
      encouraging approach to improve cartilage repair in the future. This study was
      undertaken to test if the fiber orientation (random versus aligned) of two
      different degradable polymers and a polymer intended for long term applications
      could influence primary articular chondrocytes growth and ultrastructure. A
      degradable copoly(ether)esterurethane (PDC) was synthesized via co-condensation
      of poly(p-dioxanone)diol and poly(epsilon-caprolactone)diol using an aliphatic
      diisocyanate as linker. Poly(p-dioxanone) (PPDO) was applied as commercially
      available degradable polymer, while polyetherimide (PEI) was chosen as
      biomaterial enabling surface functionalization. The fibrous scaffolds of PDC and
      PPDO were obtained by electrospinning using 1,1,1,3,3,3 hexafluoro-2-propanol
      (HFP), while for PEI dimethyl acetamide (DMAc) was applied as solvent. Primary
      porcine articular chondrocytes were seeded at different cell densities on the
      fibrous polymer scaffolds and analyzed for viability (fluorescein
      diacetate/ethidiumbromide staining), for type II collagen synthesis
      (immunolabelling), ultrastructure and orientation on the fibers (SEM: scanning
      electron microscopy). Vital chondrocytes adhered on all electrospun scaffolds
      irrespective of random and aligned topologies. In addition, the chondrocytes
      produced the cartilage-specific type II collagen on all tested polymer topologies
      suggesting their differentiated functions. SEM revealed an almost flattened
      chondrocytes shape on scaffolds with random fiber orientation: whereby
      chondrocytes growth remained mainly restricted to the scaffold surface. On
      aligned fibers the chondrocytes exhibited a more spindle-shaped morphology with
      rougher cell surfaces but only a minority of the cells aligned according to the
      fibers. As a next step the reduction of the fiber diameter of electrospun
      scaffolds should be addressed as an important parameter to mimic cartilage ECM
      structure.

PMID- 22975947
TI  - Viability and function of primary human endothelial cells on smooth poly(ether
      imide) films.
AB  - Poly(ether imide) (PEI) is being explored as potential biomaterial for
      cardiovascular applications. Different studies showed that human umbilical venous
      endothelial cells (HUVEC) are able to adhere and proliferate on PEI membranes
      (R(q) = 13.20 +/- 1.58 nm). A recently published study revealed evidence for much
      lower platelet adhesion on very smooth PEI-films (R(q) = 2.37 +/- 1.40 nm).
      Therefore, we explored whether primary human venous endothelial cells (HUVEC) are
      able to adhere and proliferate on such very smooth PEI-films compared to tissue
      cultured polystyrene (TCP) as reference material. Cytotoxicity testing revealed
      that PEI had a slight cytotoxic effect on HUVEC accompanied by a marginal reduced
      integrity of the plasma membrane and a significant lower mitochondrial activity.
      However long-term seeding experiments up to eleven days exhibited that HUVEC were
      able to proliferate on the PEI-films till confluence (TCP 96,190 +/- 18,289
      cells/cm(2); PEI 91,590 +/- 19,583 cells/cm(2)). Further studies are planned to
      monitor the influence of shear force on the endothelial cell monolayer in a
      dynamic test system to determine its stability in view of shear resistant
      endothelialization of PEI for cardiovascular devices.

PMID- 22975948
TI  - Behaviour of fibroblasts on water born acrylonitrile-based copolymers containing
      different cationic and anionic moieties.
AB  - The chemical composition of a substrate can influence the adhesion, viability and
      proliferation of cells seeded on the substrate. The aim of this work was to
      investigate the influence of different cationic or anionic moieties in
      acrylonitrile-based copolymers on the interaction with fibroblasts. A series of
      ten different types of acrylonitrile-based copolymers with a random sequence
      structure was prepared using a water born synthesis process to exclude potential
      residues of organic solvents. As charged comonomers cationic methacrylic acid-2
      aminoethylester hydrochloride (AEMA), N-3-amino-propyl-methacrylamide
      hydrochloride (APMA) and anionic 2-methyl-2-propene-1-sulfonic acid sodium salt
      (NaMAS) were utilized. By application of a specific sintering procedure the
      copolymer materials were processed into transparent disks for conducting cell
      tests in direct contact. The copolymers were analyzed with respect to their
      composition and surface properties. Cytotoxicity tests of the polymer extracts,
      as well as of the disks were performed with L929 mouse fibroblasts. All
      copolymers showed no cytotoxic effects. Furthermore, for higher molar ratios of
      AEMA an increase in cell growth could be observed, which might be a hint that
      higher charge densities are favorable for the proliferation of L929 cells.

PMID- 22975949
TI  - Adherence and viability of primary human keratinocytes and primary human dermal
      fibroblasts on acrylonitrile-based copolymers with different concentrations of
      positively charged functional groups.
AB  - As shown in several studies, various properties of biomaterials such as
      stiffness, surface roughness, chemical composition or the amount of functional
      groups at the surface can influence adhesion, viability, proliferation and
      functionalities of cells. The aim of this work was to explore whether a cell
      selective effect could be achieved for acrylonitrile-based copolymers containing
      different contents of positively charged functional groups, which were introduced
      by incorporation of methacrylic acid-2-aminoethylester hydrochloride (AEMA)
      units. The p(AN-co-AEMA) copolymers were synthesized by suspension polymerization
      in water and processed into disk shaped test specimen via a sintering process to
      ensure the absence of organic solvents in the copolymers. Copolymers with an AEMA
      content of 1.4, 1.6, and 4.4 mol-% were investigated according to their cell
      selective capacity, which should support the adhesion, viability and
      proliferation of keratinocytes, while the adherence of fibroblasts should rather
      be disabled. The test samples were seeded with primary human keratinocytes and
      primary human dermal fibroblasts in mono- as well as in co-cultures. Tissue
      culture plate polystyrene (TCP) was used to control the physiologic growth of the
      cells. Density and viability of attached and non-adherent cells were analyzed by
      live/dead staining, lactate dehydrogenase (LDH) assay and flow cytometry with
      DAPI staining. For the assured discrimination of adherent cell types in coculture
      a keratin/vimentin-staining was performed. On copolymers with 4.4 mol-% AEMA
      adherent keratinocytes in monoculture and cocultured keratinocytes and
      fibroblasts showed a higher viability, a lower impairment of cell membranes and
      higher densities of viable cells compared to both other copolymers. For adherent
      fibroblasts these parameters did not differ between the copolymers and an
      increasing ratio of keratinocytes to fibroblasts in cocultures were found with
      increasing AEMA content. The results showed that keratinocytes and fibroblasts
      can be influenced by copolymers with different contents of positively charged
      functional groups. Since the tendency of a better adherence and viability of
      keratinocytes with increasing amounts of positively charged functional groups was
      shown, the potential enhancement by further increase of the amount of positively
      charged functional groups shall be tested in a future study.

PMID- 22975950
TI  - Effect of cytochrome P450-dependent epoxyeicosanoids on Ristocetin-induced
      thrombocyte aggregation.
AB  - Epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 (CYP)-dependent
      epoxidation of arachidonic acid (AA) inhibit thrombocyte adhesion to the vascular
      wall. Upon dietary omega-3 fatty acid supplementation, EETs are partially
      replaced by eicosapentaenoic acid (EPA)-derived epoxyeicosatetraenoic acids
      (EEQs) and docosahexaenoic acid (DHA)-derived epoxydocosapentaenoic acids (EDPs).
      We hypothesized that the omega-3 epoxy-metabolites may exhibit superior anti
      thrombogenic properties compared to their AA-derived counterparts. To test this
      hypothesis, we analyzed the effects of 11,12-EET, 17,18-EEQ and 19,20-EDP on
      Ristocetin-induced thrombocyte aggregation (RITA), a process that mimics
      thrombocyte adhesion to the vascular wall. The eicosanoids were added for 5, 30,
      or 60 minutes to thrombocyte-rich plasma freshly prepared immediately after blood
      collection from stringently selected apparently healthy subjects. Thrombocyte
      aggregation was then induced by Ristocetin (0.75 mg/mL) and assessed by
      turbidimetric measurements. After 60 minutes of preincubation, all three epoxy
      metabolites significantly decreased the rate of RITA. 17,18-EEQ and 19,20-EDP
      were effective already at 1 MUM, whereas 5-fold higher concentrations were
      required with 11,12-EET. Addition of AUDA, an inhibitor of the soluble epoxide
      hydrolase, potentiated the effect of 17,18-EEQ resulting in a significant further
      decrease of the velocity as well as amplitude of the aggregation process. In
      contrast to their profound effects on RITA, none of the epoxy-metabolites was
      effective in reducing collagen- or ADP-induced thrombocyte aggregation. These
      results indicate a highly specific role of CYP-eicosanoids in preventing
      thromboembolic events and suggest that the formation of 17,18-EEQ and 19,20-EDP
      may contribute to the anti-thrombotic effects of omega-3 fatty acids.

PMID- 22975951
TI  - The influence of polymer scaffolds on cellular behaviour of bone marrow derived
      human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate
      into a variety of cell types. Therefore, they are widely explored in regenerative
      medicine. The interaction of MSCs with biomaterials is of great importance for
      cell proliferation, differentiation and function, and can be strongly influenced
      by numerous factors, such as the chemical nature and the mechanical properties of
      the material surface. In this study, we investigated the interaction of bone
      marrow derived human MSCs with different amorphous and transparent polymers
      namely polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI),
      polyetherurethane (PEU) and poly(styrene-co-acrylonitrile) (PSAN). To ensure that
      the MSCs were solely in contact to the testing material we applied polymeric
      inserts, which were prepared from the aforementioned polymers via injection
      molding. The explored inserts exhibited a similar wettability with advancing
      contact angles ranging from 84 +/- 7 degrees  (PEU) to 99 +/- 5 degrees  (PS) and
      a surface roughness of Rq <= 0.86 MUm. The micromechanical properties determined
      by AFM indentation varied from 6 +/- 1 GPa (PEU) to 24 +/- 5 GPa (PSAN). Cells
      presented different adhesion rates on the polymer surfaces 24 hours after seeding
      (45 +/- 7% (PS), 63 +/- 1% (PC), 75 +/- 4% (PEI), 69 +/- 2% (PEU) and 61 +/- 5%
      (PSAN)). The cells could proliferate on the polymer surfaces, and the fold change
      of cell number after 16 days of culture reached to 1.93 +/- 0.07 (PS), 3.38 +/-
      0.11 (PC), 3.65 +/- 0.04 (PEI), 2.24 +/- 0.15 (PEU) and 3.36 +/- 0.09 (PSAN).
      Differences in cell apoptosis could be observed during the culture. After 7 days,
      the apoptosis of cells on PC, PEI and PSAN decreased to a level comparable to
      that on standard tissue culture plate (TCP). All of the tested polymers exhibited
      low cytotoxicity and allowed high cell viability. Compared to cells on TCP, cells
      on PC and PEI showed similar morphology, distribution as well as F-actin
      cytoskeleton organization, whereas cells on PSAN were distributed less evenly and
      cells on PEU were less oriented. Cells were more likely to form clusters on PS.
      Conclusively, we demonstrated the influence of polymer substrates on the cellular
      behaviour of MSCs, which could be included in the development of novel design
      concepts based on polymeric biomaterials.

PMID- 22975952
TI  - Immunological evaluation of polystyrene and poly(ether imide) cell culture
      inserts with different roughness.
AB  - For the successful clinical and biological application of polymers, their
      interaction with cells, tissues, and body fluids has to be well characterized. In
      order to investigate how the physical, chemical, and mechanical properties of
      candidate biomaterials influence cell behaviours, the testing sample is usually
      placed in commercially available cell culture plates. Thus, not only the testing
      sample itself but also the culture dish material might influence the cell
      behaviour. Therefore, an insert system was created to exclude this influence and
      allow investigations of the testing material solely. In this study micropatterned
      inserts prepared from polystyrene (PS) as well as from poly(ether imide) (PEI)
      with three different roughness levels of i) Rq = 0.29 MUm (PS) and 0.23 MUm
      (PEI); ii) Rq = 3.47 MUm (PS) and 3.92 MUm (PEI); and iii) Rq = 22.16 MUm
      [corrected] (PS) and 22.65 MUm (PEI) were explored with regard of their immuno
      compatibility including the determination of potential contaminations with
      endotoxins or other microbial products. The endotoxin levels of the inserts were
      determined to be less than 0.07 EU/mL, which is well below the U.S. Food and Drug
      Administration limit of 0.5 EU/mL and the survival of murine macrophages cultured
      in the inserts was not impaired. Activation of early immune mechanisms such as
      complement activation and the generation of reactive oxygen species could not be
      observed. All tested materials had no influence on the cytokine secretion from
      cells of whole human blood. The investigated inserts were immuno-compatible and
      apparently free of contaminations with microbial products. The roughness of the
      inserts had no stimulatory or inhibitory effect on early immune mechanisms.
      Conclusively, the 24-well plate insert systems introduced in this study allow
      investigating the interactions of tailored surface properties such as roughness
      with many other cell types, without the disadvantage of the standard commercially
      available culture vessels influencing the biomaterial testing.

PMID- 22975953
TI  - Historical overview of nanotechnology and nanotoxicology.
AB  - Although scientists have been studying nanoscience phenomena for many decades,
      technological developments in the second half of the twentieth century provided
      valuable tools that permitted researchers to study and develop materials in the
      nanoscale size range and helped formalize nanotechnology as a scientific field.
      This chapter provides a brief history of the field of nanotechnology, with an
      emphasis on the development of nanotoxicology as a scientific field. A brief
      overview of the worldwide regulatory activities for nanomaterials is also
      presented. The future development and safe use of nanomaterials in a diverse
      range of consumer products will be interesting, intellectually challenging,
      exciting, and hopefully very beneficial for the society.

PMID- 22975954
TI  - Characterization of nanomaterials for toxicological studies.
AB  - The scientific community, regulatory agencies, environmentalists, and most
      industry representatives all agree that more effort is required to ensure the
      responsible and safe development of new nanotechnologies. Characterizing
      nanomaterials is a key aspect in this effort. There is no universally agreed upon
      minimum set of characteristics although certain common properties are included in
      most recommendations. Therefore, characterization becomes more like a puzzle put
      together with various measurements rather than a single straightforward
      analytical measurement. In this chapter, we emphasize and illustrate the
      important elements of nanoparticle characterization with a systematic approach to
      physicochemical characterization. We start with an overview describing the
      properties that are most significant to toxicological testing along with
      suggested methods for characterizing an as-received nanomaterial and then
      specifically address the measurement of size, surface properties, and imaging.

PMID- 22975955
TI  - Methods for understanding the interaction between nanoparticles and cells.
AB  - A critical view of the current toxicological methods used in nanotechnology and
      their related techniques. Hereby, toxicological effects derived from the
      intracellular accumulation and uptake will be examined. Then
      advantages/disadvantages of these methods will be discussed. Additional
      analytical techniques necessary to implement the results will be reviewed.

PMID- 22975956
TI  - Single-cell gel electrophoresis (Comet) assay in nano-genotoxicology.
AB  - The Comet assay, or single-cell gel electrophoresis assay, is an easy and simple
      yet reliable method to evaluate DNA damage in cells. Under the alkaline
      conditions of this method, DNA strand breaks and alkaline-labile sites are
      detected. Here we describe the alkaline version of the Comet assay with
      applications in testing nanoparticles.

PMID- 22975957
TI  - Single-cell nanotoxicity assays of superparamagnetic iron oxide nanoparticles.
AB  - Properly evaluating the nanotoxicity of nanoparticles involves much more than
      bulk-cell assays of cell death by necrosis. Cells exposed to nanoparticles may
      undergo repairable oxidative stress and DNA damage or be induced into apoptosis.
      Exposure to nanoparticles may cause the cells to alter their proliferation or
      differentiation or their cell-cell signaling with neighboring cells in a tissue.
      Nanoparticles are usually more toxic to some cell subpopulations than others, and
      toxicity often varies with cell cycle. All of these facts dictate that any
      nanotoxicity assay must be at the single-cell level and must try whenever
      feasible and reasonable to include many of these other factors. Focusing on one
      type of quantitative measure of nanotoxicity, we describe flow and scanning image
      cytometry approaches to measuring nanotoxicity at the single-cell level by using
      a commonly used assay for distinguishing between necrotic and apoptotic causes of
      cell death by one type of nanoparticle. Flow cytometry is fast and quantitative,
      provided that the cells can be prepared into a single-cell suspension for
      analysis. But when cells cannot be put into suspension without altering
      nanotoxicity results, or if morphology, attachment, and stain location are
      important, a scanning image cytometry approach must be used. Both methods are
      described with application to a particular type of nanoparticle, a
      superparamagnetic iron oxide nanoparticle (SPION), as an example of how these
      assays may be applied to the more general problem of determining the effects of
      nanomaterial exposure to living cells.

PMID- 22975958
TI  - Western blot analysis.
AB  - Electrophoresis and the following western blot analysis are indispensable to
      investigate biochemical changes in cells and tissues exposed to nanoparticles or
      nanomaterials. Proteins should be extracted from the cells and tissues using a
      proper method, especially when phosphorylated proteins are to be detected. It is
      important to select a good blocking agent and an appropriate pair of primary and
      peroxidase-tagged secondary antibodies to obtain good results in western blot
      analysis. One thing that may be specific to nanomaterials, and that you should
      keep in mind, is that some proteins may be adsorbed on the surface of particulate
      nanomaterials. In this chapter the whole process of western blot analysis, from
      sample preparation to quantitative measurement of target proteins, is described.

PMID- 22975959
TI  - Application of reverse transcription-PCR and real-time PCR in nanotoxicity
      research.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) is a relatively simple
      and inexpensive technique to determine the expression level of target genes and
      is widely used in biomedical science research including nanotoxicology studies
      for semiquantitative analysis. Real-time PCR allows for the detection of PCR
      amplification in the exponential growth phase of the reaction and is much more
      quantitative than traditional RT-PCR. Although a number of kits and reagents for
      RT-PCR and real-time PCR are commercially available, the basic principles are the
      same. Here, we describe the procedures for total RNA isolation by using TRI
      Reagent, for reverse transcription (RT) by M-MLV reverse transcriptase, and for
      PCR by GoTaq((r)) DNA Polymerase. And real-time PCR will be performed on an iQ5
      multicolor real-time PCR detection system by using iQTM SYBR Green Supermix.

PMID- 22975960
TI  - Deriving TC50 values of nanoparticles from electrochemical monitoring of lactate
      dehydrogenase activity indirectly.
AB  - Nanotoxicity assessment methods for nanoparticles (NPs) such as carbon nanotubes
      (CNTs), nano-Al(2)O(3), and tridecameric aluminum polycation or nanopolynuclear
      (nano-Al(13)), particularly lactate dehydrogenase (LDH) assays are reviewed. Our
      researches on electrochemically monitoring the variations of LDH activity
      indirectly in the presence of multiwalled carbon nanotubes (MWCNTs), nano-Al(13),
      and nano-Al(2)O(3) separately to derive toxic concentrations of NPs altering LDH
      activity by 50% (TC(50)) values are discussed. TC(50) values indicated that the
      toxicity order was Al (III)> MWCNTs > nano-Al(13) > nano-Al(2)O(3). Zeta
      potentials (zeta) data of these NPs in the literature proved that the surfaces of
      these NPs are charged negatively. Negatively charged surfaces might be a main
      cause in the reduction of LDH activity. Therefore, the classic LDH assays are
      doubtful to underestimate the nanotoxicities when they are applied to those NPs
      with negatively charged surfaces. These observations highlight and reconcile some
      contradictory results at present such as medium-dependent toxicity of NPs among
      the literature and develop novel analytical methods for evaluation of toxicities
      of NPs.

PMID- 22975961
TI  - Enzyme-linked immunosorbent assay of IL-8 production in response to silver
      nanoparticles.
AB  - Enzyme-linked immunosorbent assay (ELISA) for monitoring the effects of
      nanoparticles on immune cells is a conventional method of assessing the levels of
      cytokine that are released into the culture supernatant after the addition of
      nanoparticles to a macrophage culture. However, it has been found that the
      presence of nanoparticles can interfere with spectrophotometric analysis, used as
      an indicator test system; thus, it is necessary to thoroughly checked for the
      possibility of interference. In this chapter, the assessment method of cytokine
      production is covered in detail by utilizing the cytokine model produced by
      silver nanoparticles.

PMID- 22975962
TI  - Metabolomics techniques in nanotoxicology studies.
AB  - The rapid growth in the development of nanoparticles for uses in a variety of
      applications including targeted drug delivery, cancer therapy, imaging, and as
      biological sensors has led to questions about potential toxicity of such
      particles to humans. High-throughput methods are necessary to evaluate the
      potential toxicity of nanoparticles. The omics technologies are particularly well
      suited to evaluate toxicity in both in vitro and in vivo systems. Metabolomics,
      specifically, can rapidly screen for biomarkers related to predefined pathways or
      processes in biofluids and tissues. Specifically, oxidative stress has been
      implicated as a potential mechanism of toxicity in nanoparticles and is generally
      difficult to measure by conventional methods. Furthermore, metabolomics can
      provide mechanistic insight into nanotoxicity. This chapter focuses on the
      application of both LC/MS and NMR-based metabolomics approaches to study the
      potential toxicity of nanoparticles.

PMID- 22975963
TI  - Nanoparticle uptake measured by flow cytometry.
AB  - The uptake of nanoparticles by cells is an important factor to assess
      nanotoxicity. In general, the nanoparticles taken up by the cells have been
      identified by transmission electron microscope, inductively coupled plasma mass
      spectrometry, etc.; however, the methods required an immense amount of time and
      effort. Flow cytometry (FCM) has been used and developed in the fields of
      biochemistry and clinical hematology, and has advantages to analyze thousands of
      cells in seconds. We recently clarified that the side-scatter(ed) light of FCM
      could be used as a guide to measure uptake potential of nanoparticles. Here, we
      describe the protocol for screening of the uptake potential of nanoparticles
      using FCM.

PMID- 22975964
TI  - Determining biological activity of nanoparticles as measured by flow cytometry.
AB  - Flow cytometry is a powerful tool to evaluate cellular responses at the single
      cell level. Applicability to evaluating biological activity of in vitro and in
      vivo exposure to compounds is limited only by the number of fluorochrome emission
      spectra a particular instrument can detect and the availability of antibodies
      specific for a particular cellular protein. Here, I describe the general method
      considerations and provide an example experimental design for utilizing flow
      cytometry to evaluate the biological activity of nanoparticles on primary murine
      immune cells.

PMID- 22975965
TI  - Whole cell impedance biosensoring devices.
AB  - Nanotechnology is rapidly growing and has great potential in various fields such
      as biomedical engineering, drug delivery, environmental health, pharmaceutical
      industries and even electronics and communication technologies. However, with
      this rapid development, these new nanoscale materials (including nanotubes,
      nanowires, nanowhiskers, fullerenes or buckyballs, and quantum dots) might have
      unintended human health and environmental hazards. Testing for toxicological
      parameters is a necessary first step toward ensuring the compatibility of
      nanomaterials for medical applications and for the safety of the environment.
      Here, we describe an array formatted electrical impedance sensing (EIS) system
      that is capable of measuring nanotoxicity in real time.

PMID- 22975966
TI  - Free energy calculation of permeant-membrane interactions using molecular
      dynamics simulations.
AB  - Nanotoxicology, the science concerned with the safe use of nanotechnology and
      nanostructure design for biological applications, is a field of research that has
      recently received great attention, as a result of the rapid growth in
      nanotechnology. Many nanostructures are of a scale and chemical composition
      similar to many biomolecular environments, and recent papers have reported
      evident toxicity of selected nanoparticles. Molecular simulations can help
      develop a mechanistic understanding of how structural properties affect
      bioactivity. In this chapter, we describe how to compute the free energy of
      interactions between cellular membranes and benzene, the main constituent of some
      toxic carbonaceous particles, with well-tempered metadynamics. This algorithm
      reconstructs the free energy surface and accelerates rare events in a coarse
      grained representation of the system.

PMID- 22975967
TI  - Screening of fullerene toxicity by hemolysis assay.
AB  - Fullerene is a compound formed during carbon burst that has been produced
      synthetically starting from the 1990s. The spherical shape and the characteristic
      carbon bonds of this allotrope (C(60)) have made it a suitable molecule for many
      applications. During the last decade, the low aqueous solubility of this molecule
      has been improved by chemical functionalization allowing the use of fullerene
      derivatives in biological fluids. The characterization of the toxicity potential
      of fullerenes is therefore of growing interest for any biomedical application.
      Intravenous injection is one of the possible routes of their administrations and
      therefore red blood cells are among the first targets of fullerene cytotoxicity.
      Human red blood cells are easily available and separated from plasma. Membrane
      disruption by toxic compounds is easily detected in red blood cells as release of
      hemoglobin in the cell medium, which can be assayed spectrophotometrically at
      lambda = 415 nm. Due to the high molar extinction coefficient of hemoglobin, the
      assay can be performed on a small amount of both red blood cells and the test
      compounds, which might be available only in small quantities. So, the hemolysis
      assay is a simple screening test, whose results can guide further investigations
      on cytotoxicity in more complex experimental models.

PMID- 22975968
TI  - Assessment of in vitro skin irritation potential of nanoparticles: RHE model.
AB  - The skin irritation test is designed for the prediction of acute skin irritation
      of nanoparticles by measurement of its cytotoxic effect, as reflected in the MTT
      assay, on the Reconstructed Human Epidermis (RHE) model. RHE tissues are
      commercially available.

PMID- 22975969
TI  - In vivo methods of nanotoxicology.
AB  - The new field of nanotoxicology is steadily emerging in parallel with rapid
      advances made in nanotechnology to evaluate biological impact of intended and non
      intended nanomaterial exposure over time as their human applications constantly
      increase. Over the last decade nanotoxicology methods have mostly relied on in
      vitro cell-based characterizations that do not account for the complexity of in
      vivo systems with respect to biodistribution, metabolism, hematology, immunology,
      and neurological ramifications. Comprehensive in vivo studies addressing the
      toxicity of nanoscale materials are scarce mainly because the field is still
      nascent. Efforts in standardizing methodology to study the in vivo safety of
      these materials are currently undertaken by various government agencies and
      research organizations. Here, we discuss the need for in vivo nanotoxicity
      studies, outline some of the important methods, and comment on practical
      considerations in carrying out such studies.

PMID- 22975970
TI  - The luminescent bacteria test to determine the acute toxicity of nanoparticle
      suspensions.
AB  - Luminescent bacteria, Vibrio fischeri, is used in an ecotoxicological test to
      determine toxicity of water samples. In comparison to other ecotoxicological
      tests, the use of luminescent bacteria reports final toxicity values in a short
      time (minutes). Luminescent toxicity test can be used to determine toxicity of
      nanoparticles suspensions.

PMID- 22975971
TI  - The primacy of physicochemical characterization of nanomaterials for reliable
      toxicity assessment: a review of the zebrafish nanotoxicology model.
AB  - Engineered nanomaterials (ENMs) have become increasingly prevalent in the past
      two decades in academic, medical, commercial, and industrial settings. The unique
      properties imbued with nanoparticles, as the physiochemical properties change
      from the bulk material to the surface atoms, present unique and often challenging
      characteristics that larger macromolecules do not possess. While nanoparticle
      characteristics are indeed exciting for unique chemistries, surface properties,
      and diverse applications, reports of toxicity and environmental impacts have
      tempered this enthusiasm and given cause for an exponential increase for
      concomitant nanotoxicology assessment. Currently, nanotoxicology is a steadily
      growing with new literature and studies being published more frequently than ever
      before; however, the literature reveals clear, inconsistent trends in
      nanotoxicological assessment. At the heart of this issue are several key problems
      including the lack of validated testing protocols and models, further compounded
      by inadequate physicochemical characterization of the nanomaterials in question
      and the seminal feedback loop of chemistry to biology back to chemistry.
      Zebrafish (Danio rerio) are emerging as a strong nanotoxicity model of choice for
      ease of use, optical transparency, cost, and high degree of genomic homology to
      humans. This review attempts to amass all contemporary nanotoxicology studies
      done with the zebrafish and present as much relevant information on
      physicochemical characteristics as possible. While this report is primarily a
      physicochemical summary of nanotoxicity studies, we wish to strongly emphasize
      that for the proper evolution of nanotoxicology, there must be a strong marriage
      between the physical and biological sciences. More often than not, nanotoxicology
      studies are reported by groups dominated by one discipline or the other.
      Regardless of the starting point, nanotoxicology must be seen as an iterative
      process between chemistry and biology. It is our sincere hope that the future
      will introduce a paradigm shift in the approach to nanotoxicology with
      multidisciplinary groups for data analysis to produce predictive and correlative
      models for the end goal of rapid preclinical development of new therapeutics into
      the clinic or insertion into environmental protection.

PMID- 22975972
TI  - Application of embryonic and adult zebrafish for nanotoxicity assessment.
AB  - As an emerging model for toxicological studies, zebrafish has been explored for
      nanotoxicity assessment. In addition to endpoint examination of embryo/fish
      mortality and/or developmental disorders, molecular analyses of differential gene
      expression have also been employed to evaluate toxic effects associated with the
      exposure to nanomaterials. Here, we describe zebrafish-based assays, including
      both embryo and adult, for evaluation of nanotoxicity caused by metal oxide
      nanoparticles (NPs), in particular, zinc oxide (ZnO) and titanium oxide (TiO(2))
      nanoparticles.

PMID- 22975973
TI  - Applications of subsurface microscopy.
AB  - Exploring the interior of a cell is of tremendous importance in order to assess
      the effects of nanomaterials on biological systems. Outside of a controlled
      laboratory environment, nanomaterials will most likely not be conveniently
      labeled or tagged so that their translocation within a biological system cannot
      be easily identified and quantified. Ideally, the characterization of
      nanomaterials within a cell requires a nondestructive, label-free, and subsurface
      approach. Subsurface nanoscale imaging represents a real challenge for
      instrumentation. Indeed the tools available for high resolution characterization,
      including optical, electron or scanning probe microscopies, mainly provide
      topography images or require taggants that fluoresce. Although the intercellular
      environment holds a great deal of information, subsurface visualization remains a
      poorly explored area. Recently, it was discovered that by mechanically perturbing
      a sample, it was possible to observe its response in time with nanoscale
      resolution by probing the surface with a micro-resonator such as a
      microcantilever probe. Microcantilevers are used as the force-sensing probes in
      atomic force microscopy (AFM), where the nanometer-scale probe tip on the
      microcantilever interacts with the sample in a highly controlled manner to
      produce high-resolution raster-scanned information of the sample surface. Taking
      advantage of the existing capabilities of AFM, we present a novel technique, mode
      synthesizing atomic force microscopy (MSAFM), which has the ability to probe
      subsurface structures such as non-labeled nanoparticles embedded in a cell. In
      MSAFM mechanical actuators (PZTs) excite the probe and the sample at different
      frequencies as depicted in the first figure of this chapter. The nonlinear nature
      of the tip-sample interaction, at the point of contact of the probe and the
      surface of the sample, in the contact mode AFM configuration permits the mixing
      of the elastic waves. The new dynamic system comprises new synthesized imaging
      modes, resulting from sum- and difference-frequency generation of the driving
      frequencies. The specific electronics of MSAFM allows the selection of individual
      modes and the monitoring of their amplitude and phase. From these quantities of
      various synthesized modes a series of images can be acquired. The new images
      contain subsurface information, thus revealing the presence of nanoparticles
      inside the cells.

PMID- 22975974
TI  - Application of ICP-MS for the study of disposition and toxicity of metal-based
      nanomaterials.
AB  - Many nanomaterials, such as quantum dots, nano-gold, nano-silver, nano-ZnO, etc.,
      consist of metal components. When these metal-based nanomaterials are used for
      biological applications, their biological safety must be evaluated. The
      biological disposition (ADME: absorption, deposition, metabolism, and
      elimination) of these nanomaterials need to be evaluated. Such evaluation can be
      made via tracking of the metallic constituents of the nanoparticles in various
      tissues and organs after exposure. Although atomic absorption (AA) spectrometry
      is traditionally used for metal analyses, inductively couple plasma mass
      spectrometry (ICP-MS) is a more modern and preferred technique for metal
      analyses. ICP-MS has distinct advantages over the traditional AA technique by
      being much more sensitive, efficient, and effective. Because the metallic
      contents in nanomaterials are usually of very minute amounts, the use of ICP-MS
      for their tracking is recommended. Specifics of applications and detailed
      technical protocols for ICP-MS analyses are provided. Some study results on
      quantum dots (QDs) and nano-gold (AuNP) with ICP-MS are also illustrated.

PMID- 22975975
TI  - Quantitative nanoparticle organ disposition by gel permeation chromatography.
AB  - Gel permeation chromatography (GPC) also known as size exclusion chromatography
      (SEC) is a highly valuable tool for the purification, separation, and
      characterization of synthetic and natural polymers. In this technique, the
      analyte (usually a polymer) is dissolved in a suitable solvent and is injected
      into columns made of porous inert material. The columns separate the analyte
      based on its hydrodynamic size rather than the molecular weight. GPC systems
      typically have an RI detector, UV detector, or light scattering unit attached to
      the columns. With advanced detection systems coupled to the GPC, we can obtain
      important information about polymers including their molecular weight
      distribution, average molecular mass, degree of branching in the polymers, etc.
      In addition to the separation of polymers, GPC allows for the separation of
      enzymes, nucleic acids, polysaccharides, and hormones. With regards to
      nanotoxicity, GPC can be used for the quantitative determination of tissue
      deposition of polymer nanoparticles after in vivo exposure. Understanding the
      organ specific exposure to a nanomaterial is helpful in choosing appropriate
      toxicity assays, interpreting data from other toxicity assessments, and in
      determining potential risk.

PMID- 22975976
TI  - Physiologically based pharmacokinetic modeling for nanoparticle toxicity study.
AB  - This chapter introduces the principles and development procedures for
      physiologically based pharmacokinetic (PBPK) models, and their application for
      nanoparticle toxicity studies. PBPK models describe the concentration-time or
      mass-time profiles of chemicals or nanoparticles in individual tissues and organs
      within the body. They have been used mostly for toxicology and pharmacology
      studies of small molecules, and their application for nanoparticles are in the
      early stages. Due to the biodistribution differences between nanoparticles and
      small molecules, modification may be necessary to build PBPK models for
      nanoparticles. PBPK models for nanoparticles may be applied to biodistribution
      predictions, data extrapolation, and property-biodistribution relationships, and,
      thus, can be a powerful tool in toxicity evaluation.

PMID- 22975977
TI  - Biophysical methods for assessing plant responses to nanoparticle exposure.
AB  - As nanotechnology rapidly emerges into a new industry-driven by its enormous
      potential to revolutionize electronics, materials, and medicine-exposure of
      living species to discharged nanoparticles has become inevitable. Despite the
      increased effort on elucidating the environmental impact of nanotechnology,
      literature on higher plants exposure to nanoparticles remains scarce and often
      contradictory. Here we present our biophysical methodologies for the study of
      carbon nanoparticle uptake by Allium cepa cells and rice plants. We address the
      three essential aspects for such studies: identification of carbon nanoparticles
      in the plant species, quantification of nanotransport and aggregation in the
      plant compartments, and evaluation of plant responses to nanoparticle exposure on
      the cellular and organism level. Considering the close connection between plant
      and mammalian species in ecological systems especially in the food chain, we draw
      a direct comparison on the uptake of carbon nanoparticles in plant and mammalian
      cells. In addition to the above studies, we present methods for assessing the
      effects of quantum dot adsorption on algal photosynthesis.

PMID- 22975978
TI  - In vivo nanotoxicity assays in plant models.
AB  - Increasing application of silver nanoparticles (SNPs) and zinc oxide
      nanoparticles (nZnO) in consumer products like textiles, cosmetics, washing
      machines and other household products increases their chance to reach the
      environment. Intensive research is required to assess the nanoparticles' toxicity
      to the environmental system. The toxicological effect of nanoparticles has been
      studied at the miniscule scale and requires intensive research to be conducted to
      assess its unknown effects. Plants are the primary target species which need to
      be included to develop a comprehensive toxicity profile for nanoparticles. So
      far, the mechanisms of toxicity of nanoparticles to the plant system remains
      largely unknown and little information on the potential uptake of nanoparticles
      by plants and their subsequent fate within the food chain is available. The
      phytoxicological behaviour of silver and zinc oxide nanoparticles on Allium cepa
      and seeds of Zea mays (maize), Cucumis sativus (cucumber) and Lycopersicum
      esculentum (tomato) was done. The in vitro studies on A. cepa have been done to
      check the cytotoxicological effects including mitotic index, chromosomal
      aberrations, vagrant chromosomes, sticky chromosomes, disturbed metaphase, breaks
      and formation of micronucleus. In vitro and in vivo studies on seed systems
      exposed to different concentration of nanoparticles dispersion to check
      phytotoxicity end point as root length, germination effect, adsorption and
      accumulation of nanoparticles (uptake studies) into the plant systems. In vivo
      studies in a seed system was done using phytagel medium. Biochemical studies were
      done to check effect on protein, DNA and thiobarbituric acid reactive species
      concentration. FT-IR studies were done to analyze the functional and
      conformational changes in the treated and untreated samples. The toxicological
      effects of nanoparticles had to be studied at the miniscule scale to address
      existing environment problems or prevent future problems. The findings suggest
      that the engineered nanoparticles, though having significant advantages in
      research and medical applications, requires a great deal of toxicity database to
      ascertain the biosafety and risk of using engineered nanoparticles in consumer
      products.

PMID- 22975979
TI  - Occurrence of free deaminoneuraminic acid (KDN)-containing complex-type N-glycans
      in human prostate cancers.
AB  - We previously reported on the accumulation of a substantial amount of free N
      acetylneuraminic acid (Neu5Ac)-containing complex-type N-glycans in human
      pancreatic cancer cells (Yabu M, Korekane H, Takahashi H, Ohigashi H, Ishikawa O,
      Miyamoto Y. 2013. Accumulation of free Neu5Ac-containing complex-type N-glycans
      in human pancreatic cancers. Glycoconj J, 30(3):247-256). In the present paper,
      we further extend our cancer glycomic study of human prostate cancer.
      Specifically, we demonstrate that, in addition to the free Neu5Ac-containing N
      glycans, significant amounts of free deaminoneuraminic acid (KDN, 2-keto-3-deoxy
      D-glycero-D-galacto-nononic acid)-containing N-glycans had accumulated in the
      prostate cancer tissues from four of five patients. Indeed, in one of the four
      cases, the free KDN glycans accumulated as major components in prostate cancer
      tissue. The structures of the KDN-containing free oligosaccharides were analyzed
      by a variety of methods. Specifically, we used fluorescent labeling with
      aminopyridine combined with two-dimensional mapping, KDNase digestion and mass
      spectrometry to facilitate identification. The analysis also utilized newly
      synthesized KDN-linked oligosaccharides as standards. The prostate-specific
      glycans were composed of five species having the following sequence, KDN-Gal
      GlcNAc-Man-Man-GlcNAc (alpha2,6-KDN-linked glycans being the dominant form). The
      most abundant free KDN-containing N-glycan was KDNalpha2-6Galbeta1-4GlcNAcbeta1
      2Manalpha1-3Manbeta1-4GlcNAc followed by KDNalpha2-6Galbeta1-4GlcNAcbeta1
      2Manalpha1-6Manbeta1-4GlcNAc. This is the first study to show unequivocal
      chemical evidence for the occurrence of KDN glycoconjugates in human tissues
      together with their detailed structures. These oligosaccharides might be
      developed as tumor markers, especially for prostate cancer.

PMID- 22975980
TI  - Reconstructed glycan profile for evaluation of operating status of the
      endoplasmic reticulum glycoprotein quality control.
AB  - Glycoprotein oligosaccharides function as tags for protein quality control in the
      endoplasmic reticulum (ER). Since most of proteins are glycosylated and function
      only after they are properly folded, glycoprotein glycan profiles in the ER might
      be useful to analyze various cellular status including diseases. Here, we
      examined whether ER glycan-processing profiles in diabetic rats and osteoporotic
      mice as models might have different cellular status from those of normal
      controls. Direct analysis of glycoprotein-processing profiles in the ER is often
      hampered by glycoforms that are retro-translocated to the ER from other cellular
      compartments. Moreover, when we focus on the mixture of glycoproteins as the
      processing substrates, the glycan-processing efficiencies are influenced by the
      aglycon states including their polypeptide folding. To overcome this problem, we
      reconstructed glycan profiles using ER extracts as an enzymatic source and
      synthetic glycoprotein mimetic having homogeneous aglycon as a substrate,
      resulted in disease-specific glycan profiles. To understand such differences, we
      also analyzed the activity, and expression level, of each glycan-related enzyme.
      These glycan profiles are expected to be useful indexes for operational status of
      the ER glycoprotein quality control, and may also give information to classify
      some diseases.

PMID- 22975981
TI  - The effects of acidification on human milk's cellular and nutritional content.
AB  - OBJECTIVE: Fortification of human milk for preterm infants is necessary and a
      common newborn intensive care practice. Currently, acidified human milk as part
      of a human milk fortifier is being fed to preterm infants. However, there are
      little data on the acidification effects on mother's milk. The aim of this study
      is to determine the effects of acidification on human milk's cellular and
      nutritional composition. STUDY DESIGN: One hundred milk samples were collected
      from eight mothers who had infants in the neonatal intensive care unit. All milk
      samples were frozen at 4  degrees C. The frozen samples were thawed and divided
      into two equal aliquots, control and acidified. The control milk sample had its
      pH determined while the other sample was acidified to pH 4.5. Each milk sample
      was examined for pH, white cells, total protein, creamatocrit, lipase activity
      and free fatty acids. RESULT: Mean pH of the human milk control was 6.8 +/- 0.1
      (M +/- s.d.) with the acidified milk at 4.5 +/- 0.1. Acidification caused a 76%
      decrease in white cells, a 56% decrease in lipase activity and a 14% decrease in
      the total protein but a 36% increase in the creamatocrit. CONCLUSION:
      Acidification of human milk causes significant changes of the milk's cellular and
      nutritional components that may not be beneficial to preterm infants.

PMID- 22975982
TI  - NICU patient satisfaction: how you measure counts.
AB  - OBJECTIVE: To examine whether the method of measuring patient satisfaction
      influences the results. STUDY DESIGN: All families with NICU patients discharged
      home alive to parent(s) were surveyed at 2 to 42 days post discharge with two
      parallel surveys (mailed and phone) from August 2010 to December 2011. The
      responses to the same five questions on each survey were recorded and subjected
      to statistical analysis via paired Student's t and Pearson correlation
      coefficients to see whether the two surveys yielded the same population
      attitudes. RESULT: Eight hundred and thirteen families were included in the
      study. Seven hundred and sixty three (93.8%) completed the phone survey and 237
      (29.2%) completed the mail in survey. Three of the five questions yielded
      significantly different answers between mailed and phone responses. In addition,
      no significant linear correlation between mail and survey could be found for the
      other two questions. CONCLUSION: As no linear correlation could be found between
      two of the five questions, a process constant mathematical value could not be
      identified. This indicates that mail survey and phone survey respondents have
      different attitudes that cannot be adjusted because of methodological measurement
      effects.

PMID- 22975983
TI  - Perioral movements and sucking pattern during bottle feeding with a novel,
      experimental teat are similar to breastfeeding.
AB  - OBJECTIVE: To measure intraoral pressure and perioral movement in infants during
      breastfeeding (BF) and feeding with experimental teat (ET). The teat has a wide
      base, firm shaft and a valve at the base, such that milk flows only when the baby
      provides a hold pressure. STUDY DESIGN: Twenty healthy term infants, between 1
      and 8 months old, were enrolled in the study. Feeding sessions (BF and ET) were
      recorded using a digital video camera. During both BF and ET feeding sessions,
      recordings during feeding were taken of jaw and throat movements (n=20) as well
      as intraoral pressure (n=18). The efficiency of milk transfer and the angle of
      the mouth were also measured. RESULT: There was no significant difference in
      either the jaw or throat movements between BF and ET. The sucking burst pattern,
      the efficiency (ml min(-1)), and the angle of the mouth did not differ between
      both feeding methods. The intraoral negative pressure observed during ET was
      significantly smaller than that observed during BF. CONCLUSION: There were no
      significant differences in perioral movements. Although the value was smaller, a
      hold pressure was observed during ET. From these results, the novel, ET may
      decrease BF problems related to bottle use.

PMID- 22975984
TI  - Nighttime cardiac sympathetic hyper-activation in young primary insomniacs.
AB  - PURPOSE: A growing literature supports the association between insomnia and
      cardiovascular risk. Since only few studies have provided empirical evidence of
      hyper-activation of the cardiovascular system in insomniacs, the aim of the
      present study was to analyze cardiac autonomic responses in primary insomnia.
      METHODS: Impedance cardiography and heart rate variability (HRV) measures were
      assessed in 9 insomniacs and 9 good sleepers during a night of polysomnographic
      recording. RESULTS: Insomniacs were found to be characterized by a constant
      sympathetic hyper-activation which was maintained all night, as suggested by a
      faster pre-ejection period (PEP) compared to good sleepers. In addition, only
      insomniacs showed a strong reduction in heart rate in the transition from wake to
      sleep. Both groups exhibited a reduction in cardiac output and sympathovagal
      balance, i.e., reductions in low-frequency/high-frequency ratio and increases in
      high-frequency normalized units of HRV, across the night. In addition, in our
      sample, a high physiological sympathetic activation (fast PEP) at night was found
      to be directly associated with low quality of sleep. CONCLUSIONS: These
      preliminary findings suggest that a constant cardiac sympathetic hyper-activation
      throughout the night is a main feature of primary insomnia. Our evidences support
      the association between insomnia and increased risk for cardiovascular diseases.

PMID- 22975985
TI  - First molecular identification and characterization of classical swine fever
      virus isolates from Nepal.
AB  - Classical swine fever (CSF) is a major constraint to pig production worldwide,
      and in many developing countries, the epidemiological status is unknown. Here,
      for the first time, molecular identification and characterization of CSFV
      isolates from two recent outbreaks in Nepal are presented. Analysis of full
      length E2-encoding sequences revealed that these isolates belonged to CSFV
      subgenotype 2.2 and had highest genetic similarity to isolates from India. Hence,
      for CSFV, Nepal and India should be regarded as one epidemiological unit. Both
      Nepalese isolates exhibited significant sequence differences, excluding a direct
      epidemiological connection and suggesting that CSFV is endemic in that country.

PMID- 22975986
TI  - Molecular identification of enteroviruses associated with aseptic meningitis in
      children from India.
AB  - We identified and characterized enteroviruses associated with aseptic meningitis
      in children between April 2009 and March 2010. Enterovirus RNA was detected in 51
      (45.5 %) of 112 CSF samples. Molecular typing by RT-PCR and sequencing of a
      partial VP1 region revealed the predominance of echovirus (ECV) 32 (n = 20),
      followed by ECV 11 (n = 10), ECV 13 and ECV 14 (n = 5 each), coxsackievirus (CV)
      B3 and CV B6 (n = 3 each), CV A2, CV A10 and ECV 30 (n = 1 each). Phylogenetic
      analysis of ECV 32 showed 0 to 4 % sequence divergence among strains of the
      present study and 20-23 % from the prototype Puerto Rico strain at the nucleotide
      level. This is the first report of ECV 32 associated with an aseptic meningitis
      epidemic and identification of seven different enterovirus serotypes (CV A2, CV
      A10, CV B3, CV B6, ECV 13, ECV 14 and ECV 32) in meningitis cases from India.

PMID- 22975987
TI  - Why do sweets fatten our livers?

PMID- 22975988
TI  - Distribution pattern of polycyclic aromatic hydrocarbons in particle-size
      fractions of coking plant soils from different depth.
AB  - The concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) in four
      size fractions (<2, 2-20, 20-200, >200 MUm) in soils at different depth from a
      heavily contaminated crude benzol production facility of a coking plant were
      determined using GC-MS. Vertically, elevated total PAHs concentrations were
      observed in the soils at 3.0-4.5 m (layer B) and 6.0-7.5 m (layer C), relatively
      lower at 1.5-3.0 m (layer A) and 10.5-12.0 m (layer D). At all sampling sites,
      the silt (2-20 MUm) contained the highest PAHs concentration (ranged from 726 to
      2,711 mg/kg). Despite the substantial change in PAHs concentrations in soils with
      different particle sizes and lithologies, PAHs composition was similarly
      dominated by 2-3 ring species (86.5-98.3 %), including acenaphthene, fluorene,
      and phenanthrene. For the contribution of PAHs mass in each fraction to the bulk
      soil, the 20-200 MUm size fraction had the greatest accumulation of PAHs in loamy
      sand layers at 1.0-7.5 m, increasing with depth; while in deeper sand layer at
      10.5-12.0 m, the >200 MUm size fraction showed highest percentages and
      contributed 81 % of total PAHs mass. For individual PAH distribution, the 2-3
      ring PAHs were highly concentrated in the small size fraction (<2 and 2-20 MUm);
      the 4-6 ring PAHs showed the highest concentrations in the 2-20 MUm size
      fraction, increasing with depth. The distribution of PAHs was primarily
      determined by the sorption on soil organic matter and the characteristics of
      PAHs. This research should have significant contribution to PAH migration study
      and remediation design for PAHs-contaminated sites.

PMID- 22975989
TI  - No country for old men: street use and social diet in urban Newcastle.
AB  - Within affluent societies, people who grow up in deprived areas begin
      reproduction much earlier than their affluent peers, and they display a number of
      other behaviors adapted to an environment in which life will be short. The
      psychological mechanisms regulating life-history strategies may be sensitive to
      the age profile of the people encountered during everyday activities. We
      hypothesized that this age profile might differ between environments of different
      socioeconomic composition. We tested this hypothesis with a simple observational
      study comparing the estimated age distribution of people using the streets in an
      affluent and a socioeconomically deprived neighborhood which were closely matched
      in other ways. We were also able to use the UK census to compare the age profile
      of observed street users with the actual age profile of the community. We found
      that people over 60 years of age were strikingly less often observed on the
      street in the deprived than in the affluent neighborhood, whereas young adults
      were observed more often. These differences were not reflections of the different
      age profiles of people who lived there, but rather of differences in which
      residents use the streets. The way people use the streets varies with age in
      different ways in the affluent and the deprived neighborhoods. We argue that
      chronic exposure to a world where there are many visible young adults and few
      visible old ones may activate psychological mechanisms that produce fast life
      history strategies.

PMID- 22975990
TI  - Adjusting for confounding by neighborhood using generalized linear mixed models
      and complex survey data.
AB  - When investigating health disparities, it can be of interest to explore whether
      adjustment for socioeconomic factors at the neighborhood level can account for,
      or even reverse, an unadjusted difference. Recently, we proposed new methods to
      adjust the effect of an individual-level covariate for confounding by unmeasured
      neighborhood-level covariates using complex survey data and a generalization of
      conditional likelihood methods. Generalized linear mixed models (GLMMs) are a
      popular alternative to conditional likelihood methods in many circumstances.
      Therefore, in the present article, we propose and investigate a new adaptation of
      GLMMs for complex survey data that achieves the same goal of adjusting for
      confounding by unmeasured neighborhood-level covariates. With the new GLMM
      approach, one must correctly model the expectation of the unmeasured neighborhood
      level effect as a function of the individual-level covariates. We demonstrate
      using simulations that even if that model is correct, census data on the
      individual-level covariates are sometimes required for consistent estimation of
      the effect of the individual-level covariate. We apply the new methods to
      investigate disparities in recency of dental cleaning, treated as an ordinal
      outcome, using data from the 2008 Florida Behavioral Risk Factor Surveillance
      System (BRFSS) survey. We operationalize neighborhood as zip code and merge the
      BRFSS data with census data on ZIP Code Tabulated Areas to incorporate census
      data on the individual-level covariates. We compare the new results to our
      previous analysis, which used conditional likelihood methods. We find that the
      results are qualitatively similar.

PMID- 22975993
TI  - Adipose tissue-derived mesenchymal stem cells: a fat chance of curing kidney
      disease?
AB  - Many kidney diseases are associated with inflammation and altered immune
      response. Mesenchymal stem cells (MSCs) are known for their anti-inflammatory
      properties and immune modulation. Demonstration that the phenotype and
      immunosuppressive ability of adipose tissue-derived MSCs are not affected by
      human kidney disease or uremic serum might have clinical significance if
      autologous adipose tissue-derived MSCs can be tested to prove their long-term
      safety and efficacy in treating kidney disease.

PMID- 22975994
TI  - Interaction of receptor for advanced glycation end products with advanced
      oxidation protein products induces podocyte injury.
AB  - Chronic kidney disease (CKD) is characterized by progressive decline in renal
      function. Podocyte dropouts contribute to the pathogenesis of diabetic and
      nondiabetic CKD. Zhou and colleagues demonstrate that the association between
      advanced oxidation protein products (AOPPs) and receptor for advanced glycation
      end products (RAGE) elicited podocyte injuries, using cultured podocytes and mice
      injected with AOPPs. This study suggests that the blockade of RAGE is preventive
      and therapeutic against podocyte apoptosis caused by oxidative stress-related
      AOPPs in CKD.

PMID- 22975995
TI  - The mitochondrial SIRT1-PGC-1alpha axis in podocyte injury.
AB  - Dysfunction of mitochondria in podocytes is believed to be a trigger of injury
      and contributes to progressive glomerular sclerosis; however, the mechanisms had
      not been fully understood. Yuan et al. report involvement of SIRT1 (a homolog of
      the life-extending gene sir2 in mammals) and PPAR-gamma coactivator 1alpha, a
      major regulator of oxidative metabolism, in mitochondria during podocyte injury.
      This information will be important in exploration of the mechanisms and future
      treatment of glomerular sclerosis.

PMID- 22975996
TI  - Omental wrapping of a peritoneal dialysis catheter.

PMID- 22975997
TI  - Massive bilateral nephromegaly in an infant.

PMID- 22975998
TI  - Sequencing of two sunflower chlorotic mottle virus isolates obtained from
      different natural hosts shed light on its evolutionary history.
AB  - Sunflower chlorotic mottle virus (SuCMoV), the most prevalent virus of sunflower
      in Argentina, was reported naturally infecting not only sunflower but also weeds.
      To understand SuCMoV evolution and improve the knowledge on its variability, the
      complete genomic sequences of two SuCMoV isolates collected from Dipsacus
      fullonum (-dip) and Ibicella lutea (-ibi) were determined from three overlapping
      cDNA clones and subjected to phylogenetic and recombination analyses. SuCMoV-dip
      and -ibi genomes were 9,953-nucleotides (nt) long; their sequences contained an
      open reading frame of 9,561 nucleotides, which encoded a polyprotein of 3,187
      amino acids flanked by a 5'-noncoding region (NCR) of 135 nt and a 3'-NCR of 257
      nt. SuCMoV-dip and -ibi genome nucleotide sequences were 90.9 identical and
      displayed 90 and 94.6 % identity to that of SuCMoV-C, and 90.8 and 91.4 %
      identity to that of SuCMoV-CRS, respectively. P1 of SuCMoV-dip and -ibi was 3-nt
      longer than that of SuCMoV-CRS, but 12-nt shorter than that of SuCMoV-C. Two
      recombination events were detected in SuCMoV genome and the analysis of d(N)/d(S)
      ratio among SuCMoV complete sequences showed that the genomic regions are under
      different evolutionary constraints, suggesting that SuCMoV evolution would be
      conservative. Our findings provide evidence that mutation and recombination would
      have played important roles in the evolutionary history of SuCMoV.

PMID- 22975999
TI  - Predictive role of cytokine gene polymorphisms for the development of femoral
      head osteonecrosis.
AB  - INTRODUCTION: Osteonecrosis (ON) is a multifactorial disease that leads to hip
      destruction. Lately, much focus has been at femoral head preservation with
      nonsurgical methods. In this study we examined the polymorphisms of IL-1alpha, IL
      1R, IL-1RA, IL-4Ralpha, IL-1beta, IL-12, gammaIFN, TGF-beta, TNF-a, IL-2, IL-4,
      IL-6 and IL-10 genes for evaluation of their contribution in ON. MATERIAL AND
      METHODS: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis
      of the polymorphisms was completed using the PCR-SSP method. Statistical analysis
      was performed using the chi<formula> ^{2}</formula> test to compare the genotype
      and allelic frequency distribution. RESULTS: The CT and GA genotypes of the IL
      1alpha (-889) and TNF-a (-238) genes were found higher in the patients (51.8% and
      10.8%, respectively) compared to the healthy donors (39.7% and 2.1%,
      respectively). In TGF-beta codon 25, the G to C polymorphism in the homozygous
      state was found in 1.8% of the patients and the C allele frequency was 8.9%,
      whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG
      genotype was 16.2% in the controls whereas in the patients was 7.2%. CONCLUSIONS:
      Based on the above, we showed that certain genotypes of the IL-1alpha, TGF-beta,
      IL-10 and TNF-a genes could be related in the pathogenesis of a complicated
      disease, such as osteonecrosis. The presence of one of the above mentioned
      polymorphisms or the simultaneous carriage of more than one may further increase
      the risk for osteonecrosis, especially in those at high risk, such as patients
      receiving corticosteroids.

PMID- 22976000
TI  - PINCH expression and its clinicopathological significance in gastric
      adenocarcinoma.
AB  - OBJECTIVE: Particularly interesting new cysteine-histidine rich protein (PINCH)
      is an important component of the local adhesion complexes and upregulated in
      several types of malignancies, and involved in the incidence and development of
      tumours. PINCH expression is also independently correlated with poorer survival
      in patients with colorectal cancer. However, there is no study of PINCH in
      gastric cancer, therefore, the aim of this project was to investigate PINCH
      expression and its clinicopathological significance in gastric adenocarcinoma.
      PATIENTS AND METHODS: PINCH expression was immunohistochemically examined in
      normal gastric mucous (n=30) and gastric adenocarcinoma (n=73), from gastric
      cancer patients. RESULTS: PINCH expression in the associated-stroma of gastric
      cancers was heterogeneous, and its positive rate (75%) was higher than that of
      normal gastric mucosa (43%, <formula>X^{2}</formula> =9.711, p=0.002). The
      stronger staining was observed at the invasive edge of tumour when compared to
      the inner area of tumour. The rate of positive PINCH (88%) in the cases with
      lymph node metastasis was higher than that (52%) in the cases without metastasis
      (<formula>X^{2}</formula>=11.151, p=0.001). PINCH expression was not correlated
      with patients' gender, age, tumour size, differentiation and invasion depth (p>
      0.05). COMCLUSION: PINCH protein might play an important role in the
      tumourigenesis and metastasis of gastric adenocarcinoma.

PMID- 22976001
TI  - piRNAs warrant investigation in Rett Syndrome: an omics perspective.
AB  - Mutations in the MECP2 gene are found in a large proportion of girls with Rett
      Syndrome. Despite extensive research, the principal role of MeCP2 protein remains
      elusive. Is MeCP2 a regulator of genes, acting in concert with co-activators and
      co-repressors, predominantly as an activator of target genes or is it a methyl
      CpG binding protein acting globally to change the chromatin state and to supress
      transcription from repeat elements? If MeCP2 has no specific targets in the
      genome, what causes the differential expression of specific genes in the Mecp2
      knockout mouse brain? We discuss the discrepancies in current data and propose a
      hypothesis to reconcile some differences in the two viewpoints. Since transcripts
      from repeat elements contribute to piRNA biogenesis, we propose that piRNA levels
      may be higher in the absence of MeCP2 and that increased piRNA levels may
      contribute to the mis-regulation of some genes seen in the Mecp2 knockout mouse
      brain. We provide preliminary data showing an increase in piRNAs in the Mecp2
      knockout mouse cerebellum. Our investigation suggests that global piRNA levels
      may be elevated in the Mecp2 knockout mouse cerebellum and strongly supports
      further investigation of piRNAs in Rett syndrome.

PMID- 22976002
TI  - The impact of either 4-R-hydroxyproline or 4-R-fluoroproline on the conformation
      and SH3m-cort binding of HPK1 proline-rich peptide.
AB  - SH3 domains are probably the most abundant molecular-recognition modules of the
      proteome. A common feature of these domains is their interaction with ligand
      proteins containing Pro-rich sequences. Crystal and NMR structures of SH3 domains
      complexes with Pro-rich peptides show that the peptide ligands are bound over a
      range of up to seven residues in a PPII helix conformation. Short proline-rich
      peptides usually adopt little or no ordered secondary structure before binding
      interactions, and consequently their association with the SH3 domain is
      characterized by unfavorable binding entropy due to a loss of rotational freedom
      on forming the PPII helix. With the aim to stabilize the PPII helix conformation
      into the proline-rich decapeptide PPPLPPKPKF (P2), we replaced some proline
      residues either with the 4(R)-4-fluoro-L-proline (FPro) or the 4(R)-4-hydroxy-L
      proline (Hyp). The interactions of P2 analogues with the SH3 domain of cortactin
      (SH3(m-cort)) were analyzed by circular dichroism spectroscopy, while CD thermal
      transition experiments have been used to determine their propensity to adopt a
      PPII helix conformation. Results show that the introduction of three residues of
      Hyp efficiently stabilizes the PPII helix conformation, while it does not improve
      the affinity towards the SH3 domain, suggesting that additional forces, e.g.,
      electrostatic interactions, are involved in the SH3(m-cort) substrate
      recognition.

PMID- 22976003
TI  - Silibinin regulates matrix metalloproteinase 3 (stromelysine1) gene expression,
      hexoseamines and collagen production during rat skin wound healing.
AB  - Silibinin (SB), a flavonoid isolated from the milk thistle, Silybum marianum, has
      been shown to exhibit protective effects against skin damage. The objective of
      the present study was to investigate the effect of topical application of SB on
      levels of stromelysine 1 (STM1) gene expression, acetyl hexoseamines and collagen
      production during skin wound healing. Full-thickness skin wounds were topically
      treated with 10% and 20% SB extract in acetonitril:olive oil (AOO) (4:1) for 30
      days, and expression level of STM1 transcript, n-acetyl glucoseamine (NAGLA), n
      acetyl galactoseamine (NAGAA) and collagen contents were analyzed on the 10th,
      20th and 30th days post wounding. SB in dose- and time-dependent manner
      accelerated wound closure time and increased levels of STM1 mRNA, hydroxyproline,
      NAGLA and NAGAA compared to the untreated and vehicle (AOO)-treated rats. The
      current study provides evidence that SB, by increasing STM1 gene expression and
      extracellular matrix constituents including glycosaminoglycans and collagen
      contents, promotes a faster wound healing process and can be used as a healing
      agent in future.

PMID- 22976004
TI  - DYT-1 gene dystonic tremor presenting as a "scan without evidence of dopaminergic
      deficit".

PMID- 22976005
TI  - Cardiomyocyte-specific deletion of survivin causes global cardiac conduction
      defects.
AB  - Survivin (Surv) belongs to the inhibitor of apoptosis protein family. Its cardiac
      specific deletion results in reduced cardiomyocyte number, increased
      cardiomyocyte size and ploidy, and development of heart failure. Its impact on
      cardiac electrophysiology is unknown. In vivo transvenous electrophysiological
      studies were carried out in adult male mice with a cardiac-specific deletion of
      survivin (Surv(-/-); n = 12) and wild-type controls (Surv(+/+); n = 12).
      Epicardial activation mapping (EAM) was performed in Langendorff-perfused hearts
      of 16 Surv(-/-) and 6 Surv(+/+) mice. Surface-ECG showed lower heart rates in
      Surv(-/-) mice (326 +/- 66 bpm vs. 440.6 +/- 39 ms; P = 0.0001), accompanied by
      significantly prolonged P waves (20.3 +/- 5.8 vs. 14.6 +/- 2.0 ms; P = 0.009), PQ
      (47.4 +/- 8.6 vs. 41.1 +/- 3.7 ms; P = 0.043), QRS- (19.5 +/- 4.8 vs. 14.0 +/-
      1.0 ms; P = 0.002) and QT-intervals (41.6 +/- 4.4 vs. 36.2 +/- 3.4 ms; P =
      0.003). The HV-interval was prolonged in Surv(-/-) mice (12.1 +/- 2.4 vs. 9.3 +/-
      1.4 ms; P = 0.0045). We found impaired sinus-nodal function (sinus node recovery
      times: 310.2 +/- 76.6 vs. 207.8 +/- 68.6 ms; P = 0.003) and AV-nodal conduction
      (Wenckebach-periodicity: 105.9 +/- 15.9 vs. 79.6 +/- 8.1 ms; P = 0.0002). EAM
      showed significant slowing and heterogeneity of conduction in the myocardium of
      Surv(-/-) mice. All Surv(-/-) mice showed spontaneous supraventricular and
      ventricular ectopic beats (P < 0.0001 vs. wildtype). Quantitative
      immunofluorescence staining for connexin43 (Cx43) revealed a decrease in both per
      cardiomyocyte and single gap junction. Surv(-/-) mice exhibit severe global
      conduction attenuations in atrial and ventricular myocardium as well as the
      specific conduction system, accompanied by lower connexin43 levels. Lack of
      susceptibility to AF and VT suggests that reduced cardiomyocyte number and
      increased size constitute determinants of electrical stableness in the heart and
      counteract potentially proarrhythmogenic connexin43 loss in Surv(-/-).

PMID- 22976006
TI  - A migratory northern ungulate in the pursuit of spring: jumping or surfing the
      green wave?
AB  - The forage-maturation hypothesis (FMH) states that herbivores migrate along a
      phenological gradient of plant development in order to maximize energy intake.
      Despite strong support for the FMH, the actual relationship between plant
      phenology and ungulate movement has remained enigmatic. We linked plant phenology
      (MODIS-normalized difference vegetation index [NDVI] data) and space use of 167
      migratory and 78 resident red deer (Cervus elaphus), using a space-time-time
      matrix of "springness," defined as the instantaneous rate of green-up. Consistent
      with the FMH, migrants experienced substantially greater access to early plant
      phenology than did residents. Deer were also more likely to migrate in areas
      where migration led to greater gains in springness. Rather than "surfing the
      green wave" during migration, migratory red deer moved rapidly from the winter to
      the summer range, thereby "jumping the green wave." However, migrants and, to a
      lesser degree, residents did track phenological green-up through parts of the
      growing season by making smaller-scale adjustments in habitat use. Despite
      pronounced differences in their life histories, we found only marginal
      differences between male and female red deer in this study. Those differences
      that we did detect pointed toward additional constraints on female space-use
      tactics, such as those posed by calving and caring for dependent offspring. We
      conclude that whereas in some systems migration itself is a way to surf the green
      wave, in others it may simply be a means to reconnect with phenological spring at
      the summer range. In the light of ubiquitous anthropogenic environmental change,
      understanding the relationship between the green wave and ungulate space use has
      important consequences for the management and conservation of migratory ungulates
      and the phenomenon of migration itself.

PMID- 22976007
TI  - Trade-offs and upper limits to signal performance during close-range vocal
      competition in gray tree frogs hyla versicolor.
AB  - Performance limitations on signal production constrain signal evolution.
      Variation in signaling performance may be related to signaler quality and
      therefore is likely to be a salient aspect of communication systems. When
      multiple signal components are involved in communication, there may be trade-offs
      between components, and performance can be measured as the degree to which
      signalers approach the upper limits of the trade-off function. We examined vocal
      performance in the gray tree frog Hyla versicolor, in which females prefer values
      of call duration and rate exceeding the usual range of variation within and among
      males. We recorded interactions between pairs of males calling on mobile
      platforms that allowed us to manipulate intermale distance and place males in
      highly competitive environments. We found that, although there was a clear upper
      boundary on the ability of males to maximize call duration and call rate
      simultaneously, call effort did not remain constant in this highly competitive
      situation. Our estimates of an upper limit to vocal performance were corroborated
      by analyses of calling behavior in the context of close-range mate attraction. We
      discuss potential constraints on signaling performance and the relevance of this
      measure of performance for both intrasexual and intersexual communication.

PMID- 22976008
TI  - Testing for ecological limitation of diversification: a case study using
      parasitic plants.
AB  - Imbalances in phylogenetic diversity could be the result of variable
      diversification rates, differing limits on diversity, or a combination of the
      two. We propose an approach to distinguish between rates and limits as the
      primary cause of phylogenetic imbalance, using parasitic plants as a model. With
      sister-taxon comparisons, we show that parasitic plant lineages are typically
      much less diverse than their autotrophic sisters. We then use age estimates for
      taxa used in the sister-taxon comparisons to test for correlations between clade
      age and clade diversity. We find that parasitic plant diversity is not
      significantly correlated with the age of the lineage, whereas there is a strong
      positive correlation between the age and diversity of nonparasitic sister
      lineages. The Ericaceae sister pair Monotropoideae (parasitic) and Arbutoideae
      (autotrophic) is sufficiently well sampled at the species level to allow more
      parametric comparisons of diversification patterns. Model fitting for this group
      supports ecological limitation in Monotropoideae and unconstrained
      diversification in Arbutoideae. Thus, differences in diversity between parasitic
      plants and their autotrophic sisters might be caused by a combination of
      ecological limitation and exponential diversification. A combination of sister
      taxon comparisons of diversity and age, coupled with model fitting of well
      sampled phylogenies of focal taxa, provides a powerful test of likely causes of
      asymmetry in the diversity of lineages.

PMID- 22976009
TI  - Phylogenetic and experimental tests of interactions among mutualistic plant
      defense traits in Viburnum (adoxaceae).
AB  - Plant traits that mediate mutualistic interactions are widespread, yet few
      studies have linked their macroevolutionary patterns with the ecological
      interactions they mediate. Here we merged phylogenetic and experimental
      approaches to investigate the evolution of two common mutualistic plant traits,
      extrafloral nectaries (EFNs) and leaf domatia. By using the flowering plant clade
      Viburnum, we tested whether macroevolutionary patterns support adaptive
      hypotheses and conducted field surveys and manipulative experiments to examine
      whether ecological interactions are concordant with evolutionary predictions.
      Phylogenetic reconstructions suggested that EFN-bearing species are monophyletic,
      whereas the evolution of domatia correlated with leaf production strategy
      (deciduous or evergreen) and climate. Domatia were also more common in the EFN
      clade, suggesting that the two traits may jointly mediate ecological
      interactions. This result was further investigated in a common-garden survey,
      where plants with domatia and EFNs on the leaf blade had more mutualistic mites
      than plants with other trait combinations, and in manipulative field experiments,
      where the traits additively increased mutualist abundance. Taken together, our
      results suggest that mutualistic traits in Viburnum are not ecologically
      independent, as they work in concert to attract and retain mutualists, and their
      long-term evolution may be influenced by complex interactions among multiple
      traits, mutualists, and geography.

PMID- 22976010
TI  - Ecological constraints on female fitness in a phytophagous insect.
AB  - Although understanding female reproduction is crucial for population demography,
      determining how and to what relative extent it is constrained by different
      ecological factors is complicated by difficulties in studying the links between
      individual behavior, life history, and fitness in nature. We present data on
      females in a natural population of the butterfly Leptidea sinapis. These data
      were combined with climate records and laboratory estimates of life-history
      parameters to predict the relative impact of different ecological constraints on
      female fitness in the wild. Using simulation models, we partitioned effects of
      male courtship, host plant availability, and temperature on female fitness.
      Results of these models indicate that temperature is the most constraining factor
      on female fitness, followed by host plant availability; the short-term negative
      effects of male courtship that were detected in the field study were less
      important in models predicting female reproductive success over the entire life
      span. In the simulations, females with more reproductive reserves were more
      limited by the ecological variables. Reproductive physiology and egg-laying
      behavior were therefore predicted to be co-optimized but reach different optima
      for females of different body sizes; this prediction is supported by the
      empirical data. This study thus highlights the need for studying behavioral and
      life-history variation in orchestration to achieve a more complete picture of
      both demographic and evolutionary processes in naturally variable and
      unpredictable environments.

PMID- 22976011
TI  - Exploring foraging decisions in a social primate using discrete-choice models.
AB  - There is a growing appreciation of the multiple social and nonsocial factors
      influencing the foraging behavior of social animals but little understanding of
      how these factors depend on habitat characteristics or individual traits. This
      partly reflects the difficulties inherent in using conventional statistical
      techniques to analyze multifactor, multicontext foraging decisions. Discrete
      choice models provide a way to do so, and we demonstrate this by using them to
      investigate patch preference in a wild population of social foragers (chacma
      baboons Papio ursinus). Data were collected from 29 adults across two social
      groups, encompassing 683 foraging decisions over a 6-month period and the results
      interpreted using an information-theoretic approach. Baboon foraging decisions
      were influenced by multiple nonsocial and social factors and were often
      contingent on the characteristics of the habitat or individual. Differences in
      decision making between habitats were consistent with changes in interference
      competition costs but not with changes in social-foraging benefits. Individual
      differences in decision making were suggestive of a trade-off between dominance
      rank and social capital. Our findings emphasize that taking a multifactor,
      multicontext approach is important to fully understand animal decision making. We
      also demonstrate how discrete-choice models can be used to achieve this.

PMID- 22976012
TI  - Iterative evolution of increased behavioral variation characterizes the
      transition to sociality in spiders and proves advantageous.
AB  - The evolution of group living is regarded as a major evolutionary transition and
      is commonly met with correlated shifts in ancillary characters. We tested for
      associations between social tendency and a myriad of abiotic variables (e.g.,
      temperature and precipitation) and behavioral traits (e.g., boldness, activity
      level, and aggression) in a clade of spiders that exhibit highly variable social
      structures (genus Anelosimus). We found that, relative to their subsocial
      relatives, social species tended to exhibit reduced aggressiveness toward prey,
      increased fearfulness toward predators, and reduced activity levels, and they
      tended to occur in warm, wet habitats with low average wind velocities. Within
      species variation in aggressiveness and boldness was also positively associated
      with sociality. We then assessed the functional consequences of within-species
      trait variation on reconstituted colonies of four test species (Anelosimus
      eximius, Anelosimus rupununi, Anelosimus guacamayos, and Anelosimus oritoyacu).
      We used colonies consisting of known ratios of docile versus aggressive
      individuals and group foraging success as a measure of colony performance. In all
      four test species, we found that groups composed of a mixture of docile and
      aggressive individuals outperformed monotypic groups. Mixed groups were more
      effective at subduing medium and large prey, and mixed groups collectively gained
      more mass during shared feeding events. Our results suggest that the iterative
      evolution of depressed aggressiveness and increased within-species behavioral
      variation in social spiders is advantageous and could be an adaptation to group
      living that is analogous to the formation of morphological castes within the
      social insects.

PMID- 22976013
TI  - Where are we now? Bergmann's rule sensu lato in insects.
AB  - Bergmann's rule states that individuals of a species/clade at higher altitudes or
      latitudes will be larger than those at lower ones. A systemic review of the known
      literature on inter- and intraspecific variation in insect size along latitudinal
      or altitudinal clines was done to see how often such clines appeared and whether
      they reflected classwide, species-specific, or experimentally biased tendencies.
      Nearly even numbers of studies showed Bergmann clines and converse-Bergmann
      clines, where insects get smaller as latitude/altitude increases. In fact, the
      majority of studies suggested no clines at all. Small ranges may have obscured
      certain clines, while giant ranges may have introduced artifacts. Researchers
      examining interspecific patterns found clines less frequently than those
      examining intraspecific patterns because of variation among species within the
      clades, which renders interspecific studies unhelpful. Bergmann's rule does not
      apply to hexapods with nearly the same consistency as it does to endothermic
      vertebrates. The validity of Bergmann's rule for any group and range of insects
      is highly idiosyncratic and partially depends on the study design. I conclude
      that studies of Bergmann's rule should focus within species and look at
      widespread but contiguous populations to account for all sources of variation
      while minimizing error.

PMID- 22976014
TI  - Antagonistic coevolution accelerates the evolution of reproductive isolation in
      tribolium castaneum.
AB  - The evolution of reproductive isolation among populations is often the result of
      selective forces. Among those, parasites exert strong selection on host
      populations and can thus also potentially drive reproductive isolation. This
      hypothesis has yet to be explicitly tested, and here we set up a
      multigenerational coevolution experiment to explore this possibility. Five lines
      of Tribolium castaneum were allowed to coevolve with their natural parasite,
      Nosema whitei; five paired lines of identical origin were maintained in the
      absence of parasites. After 17 generations, we measured resistance within and
      reproductive isolation between all lines. Host lines from the coevolution
      treatment had considerably higher levels of resistance against N. whitei than
      their paired host lines, which were maintained in the absence of parasites.
      Reproductive isolation was greater in the coevolved selection regime and
      correlated with phenotypic differentiation in parasite resistance between
      coevolved host lines. This suggests the presence of a selection-driven genetic
      correlation between offspring number and resistance. Our results show that
      parasites can be a driving force in the evolution of reproductive isolation and
      thus potentially speciation.

PMID- 22976015
TI  - Neo-allopatry and rapid reproductive isolation.
AB  - Over the past 3 centuries, many species have been dispersed beyond their natural
      geographic limits by humans, but to our knowledge, reproductive isolation has not
      been demonstrated for such neo-allopatric species. We grew seeds from three
      species of Centaurea (Centaurea solstitialis, Centaurea calcitrapa, and Centaurea
      sulphurea) that are native to Spain and have been introduced into California, and
      we tested to what extent seed production was affected by pollen source. Compared
      with within-population crosses, seed production decreased by 52% and 44%,
      respectively, when C. solstitialis and C. sulphurea from California were
      pollinated with conspecific pollen from native populations in Spain. This implies
      rapid evolution of reproductive isolation between populations in their native and
      nonnative ranges. Whether reproductive isolation has evolved following the
      introduction of other species is unknown, but additional cases are likely,
      considering the large number of neo-allopatric species.

PMID- 22976016
TI  - Eco-evolutionary community dynamics: covariation between diversity and
      invasibility across temperature gradients.
AB  - Understanding biodiversity gradients is a long-standing challenge, and progress
      requires theory unifying ecology and evolution. Here, we unify concepts related
      to the speed of evolution, the influence of species richness on diversification,
      and niche-based coexistence. We focus on the dynamics, through evolutionary time,
      of community invasibility and species richness across a broad thermal gradient.
      In our framework, the evolution of body size influences the ecological structure
      and dynamics of a trophic network, and organismal metabolism ties temperature to
      eco-evolutionary processes. The framework distinguishes ecological invasibility
      (governed by ecological interactions) from evolutionary invasibility (governed by
      local ecology and constraints imposed by small phenotypic effects of mutation).
      The model yields four primary predictions: (1) ecological invasibility declines
      through time and with increasing temperature; (2) average evolutionary
      invasibility across communities increases and then decreases through time as the
      richness-temperature gradient flattens; (3) in the early stages of
      diversification, richness and evolutionary invasibility both increase with
      increasing temperature; and (4) at equilibrium, richness does not vary with
      temperature, yet evolutionary invasibility decreases with increasing temperature.
      These predictions emerge from the "evolutionary-speed" hypothesis, which attempts
      to account for latitudinal species richness gradients by invoking faster
      biological rates in warmer, tropical regions. The model contrasts with
      predictions from other richness-gradient hypotheses, such as "niche conservatism"
      and "species energy." Empirically testing our model's predictions should help
      distinguish among these hypotheses.

PMID- 22976017
TI  - A conceptual and statistical framework for adaptive radiations with a key role
      for diversity dependence.
AB  - In this article we propose a new framework for studying adaptive radiations in
      the context of diversity-dependent diversification. Diversity dependence causes
      diversification to decelerate at the end of an adaptive radiation but also plays
      a key role in the initial pulse of diversification. In particular, key
      innovations (which in our definition include novel traits as well as new
      environments) may cause decoupling of the diversity-dependent dynamics of the
      innovative clade from the diversity-dependent dynamics of its ancestral clade. We
      present a likelihood-based inference method to test for decoupling of diversity
      dependence using molecular phylogenies. The method, which can handle incomplete
      phylogenies, identifies when the decoupling took place and which diversification
      parameters are affected. We illustrate our approach by applying it to the
      molecular phylogeny of the North American clade of the legume tribe Psoraleeae
      (47 extant species, of which 4 are missing). Two diversification rate shifts were
      previously identified for this clade; our analysis shows that the first, positive
      shift can be associated with decoupling of two Pediomelum subgenera from the
      other Psoraleeae lineages, while we argue that the second, negative shift can be
      attributed to speciation being protracted. The latter explanation yields nonzero
      extinction rates, in contrast to previous findings. Our framework offers a new
      perspective on macroevolution: new environments and novel traits (ecological
      opportunity) and diversity dependence (ecological limits) cannot be considered
      separately.

PMID- 22976018
TI  - Weak disruptive selection and incomplete phenotypic divergence in two classic
      examples of sympatric speciation: cameroon crater lake cichlids.
AB  - Recent documentation of a few compelling examples of sympatric speciation led to
      a proliferation of theoretical models. Unfortunately, plausible examples from
      nature have rarely been used to test model predictions, such as the initial
      presence of strong disruptive selection. Here I estimated the form and strength
      of selection in two classic examples of sympatric speciation: radiations of
      Cameroon cichlids restricted to Lakes Barombi Mbo and Ejagham. I measured five
      functional traits and relative growth rates in over 500 individuals within
      incipient species complexes from each lake. Disruptive selection was prevalent in
      both groups on single and multivariate trait axes but weak relative to
      stabilizing selection on other traits and most published estimates of disruptive
      selection. Furthermore, despite genetic structure, assortative mating, and
      bimodal species-diagnostic coloration, trait distributions were unimodal in both
      species complexes, indicating the earliest stages of speciation. Long waiting
      times or incomplete sympatric speciation may result when disruptive selection is
      initially weak. Alternatively, I present evidence of additional constraints in
      both species complexes, including weak linkage between coloration and morphology,
      reduced morphological variance aligned with nonlinear selection surfaces, and
      minimal ecological divergence. While other species within these radiations show
      complete phenotypic separation, morphological and ecological divergence in these
      species complexes may be slow or incomplete outside optimal parameter ranges, in
      contrast to rapid divergence of their sexual coloration.

PMID- 22976019
TI  - Crystallization of membrane proteins in bicelles.
AB  - The structural biology of membrane proteins remains a challenging field, partly
      due to the difficulty in obtaining high-quality crystals. We developed the
      bicelle method as a tool to aid with the production of membrane protein crystals.
      Bicelles are bilayer discs that are formed by a mixture of a detergent and a
      lipid. They combine the ease of use of detergents with the benefits of a lipidic
      medium. Bicelles maintain membrane proteins in a bilayer milieu, which is more
      similar to their native environment than detergent micelles. At the same time,
      bicelles are liquid at certain temperatures and they can be integrated into
      standard crystallization techniques without the need for specialized equipment.

PMID- 22976020
TI  - Vapor diffusion-controlled meso crystallization of membrane proteins.
AB  - The presented method to crystallize membrane proteins combines the advantages of
      the meso-phase crystallization method and the classical vapor diffusion
      crystallization. It allows fast screening of crystallization conditions employing
      automated liquid handlers suited for the 96-well crystallization format.

PMID- 22976021
TI  - Solution NMR studies of integral polytopic alpha-helical membrane proteins: the
      structure determination of the seven-helix transmembrane receptor sensory
      rhodopsin II, pSRII.
AB  - About 30% of the proteins encoded in the genome are expressed as membrane
      proteins but these represent <1% of all the structures solved today. In view of
      the physiological and pharmaceutical significance of membrane proteins it is
      clear that a better and more comprehensive understanding of their three
      dimensional (3D) structures at atomic resolution is required. alpha-Helical
      integral membrane proteins are generally more difficult to work with than beta
      barrel-type proteins and this has particularly been true for the polytopic
      members such as the large family of seven-helical proteins. In this chapter we
      describe the practical aspects of the solution-state NMR spectroscopy structure
      determination of the seven-helical transmembrane (7-TM) protein receptor sensory
      rhodopsin pSRII from the haloalkaliphilic archaeon Natronomonas pharaonis
      reconstituted in detergent micelles. This is the first time that a three
      dimensional structure of a 7-TM protein has been determined by NMR.

PMID- 22976022
TI  - Use of NMR saturation transfer difference spectroscopy to study ligand binding to
      membrane proteins.
AB  - Detection of weak ligand binding to membrane-spanning proteins, such as receptor
      proteins at low physiological concentrations, poses serious experimental
      challenges. Saturation transfer difference nuclear magnetic resonance (STD-NMR)
      spectroscopy offers an excellent way to surmount these problems. As the name
      suggests, magnetization transferred from the receptor to its bound ligand is
      measured by directly observing NMR signals from the ligand itself. Low-power
      irradiation is applied to a (1)H NMR spectral region containing protein signals
      but no ligand signals. This irradiation spreads quickly throughout the membrane
      protein by the process of spin diffusion and saturates all protein (1)H NMR
      signals. (1)H NMR signals from a ligand bound transiently to the membrane protein
      become saturated and, upon dissociation, serve to decrease the intensity of the
      (1)H NMR signals measured from the pool of free ligand. The experiment is
      repeated with the irradiation pulse placed outside the spectral region of protein
      and ligand, a condition that does not lead to saturation transfer to the ligand.
      The two resulting spectra are subtracted to yield the difference spectrum. As an
      illustration of the methodology, we review here STD-NMR experiments designed to
      investigate binding of ligands to the human sweet taste receptor, a member of the
      large family of G-protein-coupled receptors. Sweetener molecules bind to the
      sweet receptor with low affinity but high specificity and lead to a variety of
      physiological responses.

PMID- 22976023
TI  - How to investigate interactions between membrane proteins and ligands by solid
      state NMR.
AB  - Solid-state NMR is an established method for biophysical studies of membrane
      proteins within the lipid bilayers and an emerging technique for structural
      biology in general. In particular magic angle sample spinning has been found to
      be very useful for the investigation of large membrane proteins and their
      interaction with small molecules within the lipid bilayer. Using a number of
      examples, we illustrate and discuss in this chapter, which information can be
      gained and which experimental parameters need to be considered when planning such
      experiments. We focus especially on the interaction of diffusive ligands with
      membrane proteins.

PMID- 22976024
TI  - Identifying and measuring transmembrane helix-helix interactions by FRET.
AB  - Specific interactions between helical transmembrane domains (TMs) play essential
      roles in the mechanisms governing the folding, stability and assembly of integral
      membrane proteins. Thus, it is appealing to identify helix-helix contacts and to
      seek the structural determinants of such interactions at the molecular level.
      Here, we provide a protocol for detecting and measuring specific helix-helix
      interactions in liposomes by Forster resonance energy transfer (FRET), using
      peptides corresponding to the TM domains of an integral membrane protein. We give
      a detailed procedure and practical guidelines on how to design, prepare, handle,
      and characterize fluorescently labeled TM peptides reconstituted in large
      unilamellar lipid vesicles. We also discuss some critical aspects of FRET
      measurements to ensure the correct analysis and interpretation of spectral data.
      Our method uses tryptophan/pyrene as the donor-acceptor FRET pair, but it can be
      easily adapted to other fluorescence pairs and to other membrane mimetic
      environments. The ability to identify crucial interhelical contacts is a valuable
      tool for the study of the stability, assembly, and function of the important and
      experimentally challenging helical membrane proteins.

PMID- 22976025
TI  - Studying substrate binding to reconstituted secondary transporters by attenuated
      total reflection infrared difference spectroscopy.
AB  - The determination of protein conformational changes induced by the interaction of
      substrates with secondary transporters is an important step toward the
      elucidation of their transport mechanism. Since conformational changes in a
      protein alter its vibrational patterns, they can be detected with high
      sensitivity by infrared difference (IR(diff)) spectroscopy without the need for
      external probes. We describe a general procedure to obtain substrate-induced
      IR(diff) spectra by alternating perfusion of buffers over an attenuated total
      reflection (ATR) crystal containing an adhered film of a membrane protein
      reconstituted in lipids. As an example, we provide specific protocols to obtain
      melibiose and Na(+)-induced ATR-IR(diff) spectra of reconstituted melibiose
      permease, a sodium/melibiose co-transporter from E. coli. The presented
      methodology is applicable in principle to any membrane protein, provided that it
      can be purified and reconstituted in functional form, and appropriate substrates
      are available.

PMID- 22976026
TI  - UV-visible and infrared methods for investigating lipid-rhodopsin membrane
      interactions.
AB  - We describe experimental UV-visible and Fourier transform infrared (FTIR)
      spectroscopic methods for characterizing lipid-protein interactions for rhodopsin
      in a membrane bilayer environment. The combination of FTIR and UV-visible
      difference spectroscopy is used to monitor the structural and functional changes
      during rhodopsin activation. Investigations of how membrane lipids stabilize
      various rhodopsin photoproducts are analogous to mutating the protein in terms of
      gain or loss of function. Interpretation of the results entails a flexible
      surface model for explaining membrane lipid-protein interactions through material
      properties relevant to biological activity.

PMID- 22976027
TI  - Proteomic characterization of integral membrane proteins using thermostatted
      liquid chromatography coupled with tandem mass spectrometry.
AB  - Due to the hydrophobicity and localization of integral membrane proteins, they
      are difficult to study using conventional biochemical methods that are compatible
      with proteomic analyses. This chapter describes the coupling of multiple crucial
      steps that lead to the optimized shotgun proteomic analysis of integral membrane
      proteins while maintaining empirical topology information. Namely, a membrane
      shaving method is utilized to separate protease accessible peptides from membrane
      embedded peptides and elevated temperatures during chromatographic separation is
      utilized to augment the recovery of hydrophobic peptides for in-line analysis
      using tandem mass spectrometry. This combination of steps facilitates increased
      identification of membrane proteins while also maintaining information regarding
      protein topology.

PMID- 22976028
TI  - LITiCon: a discrete conformational sampling computational method for mapping
      various functionally selective conformational states of transmembrane helical
      proteins.
AB  - G-Protein-coupled receptors (GPCRs) are seven helical transmembrane proteins that
      mediate cell signaling thereby controlling many important physiological and
      pathological functions. GPCRs get activated upon ligand binding and trigger the
      signal transduction process. GPCRs exist in multiple inactive and active
      conformations, and there is a finite population of the active and inactive states
      even in the ligand-free condition. An understanding of the nature of the
      conformational ensemble sampled by GPCRs and the atomic level mechanism of the
      conformational transitions require a combination of computational methods and
      experimental techniques. We have developed a coarse grained discrete
      conformational sampling computational method called "LITiCon" to map the
      conformational ensemble sampled by GPCRs in the presence and absence of ligands.
      The LITiCon method can also be used to predict functional selective
      conformational states starting from the inactive state of the receptor. LITiCon
      has been applied to map the conformational ensemble of beta2-adrenergic receptor,
      a class A GPCR. We have shown that beta2-adrenergic receptor samples a larger
      conformational space in the ligand-free state and that different ligands select
      and stabilize conformations from this ensemble. In this review we describe the
      LITiCon method in detail and elucidate the uses and pitfalls of this method.

PMID- 22976029
TI  - Homology model-assisted elucidation of binding sites in GPCRs.
AB  - G protein-coupled receptors (GPCRs) are important mediators of cell signaling and
      a major family of drug targets. Despite recent breakthroughs, experimental
      elucidation of GPCR structures remains a formidable challenge. Homology modeling
      of 3D structures of GPCRs provides a practical tool for elucidating the
      structural determinants governing the interactions of these important receptors
      with their ligands. The working model of the binding site can then be used for
      virtual screening of additional ligands that may fit this site, for determining
      and comparing specificity profiles of related receptors, and for structure-based
      design of agonists and antagonists. The current review presents the protocol and
      enumerates the steps for modeling and validating the residues involved in ligand
      binding. The main stages include (a) modeling the receptor structure using an
      automated fragment-based approach, (b) predicting potential binding pockets, (c)
      docking known binders, (d) analyzing predicted interactions and comparing with
      positions that have been shown to bind ligands in other receptors, (e) validating
      the structural model by mutagenesis.

PMID- 22976030
TI  - Comparative modeling of lipid receptors.
AB  - Comparative modeling is a powerful technique to generate models of proteins from
      families already represented by members with experimentally characterized three
      dimensional structures. The method is particularly important for modeling
      membrane-bound receptors in the G Protein-Coupled Receptor (GPCR) family, such as
      many of the lipid receptors (such as the cannabinoid, prostanoid,
      lysophosphatidic acid, sphingosine 1-phosphate, and eicosanoid receptor family
      members), as these represent particularly challenging targets for experimental
      structural characterization methods. Although challenging modeling targets, these
      receptors have been linked to therapeutic indications that vary from nociception
      to cancer, and thus are of interest as therapeutic targets. Accurate models of
      lipid receptors are therefore valuable tools in the drug discovery and
      optimization phases of therapeutic development. This chapter describes the
      construction and evaluation of comparative structural models of lipid receptors
      beginning with the selection of template structures.

PMID- 22976031
TI  - Quantification of structural distortions in the transmembrane helices of GPCRs.
AB  - A substantial part of the structural and much of the functional information about
      G protein-coupled receptors (GPCRs) comes from studies on rhodopsin. Thus,
      analysis tools for detailed structure comparison are key to see to what extent
      this information can be extended to other GPCRs. Among the methods to evaluate
      protein structures and, in particular, helix distortions, HELANAL has the
      advantage that it provides data (local bend and twist angles) that can be easily
      translated to structural effects, as a local opening/tightening of the helix.In
      this work I show how HELANAL can be used to extract detailed structural
      information of the transmembrane bundle of GPCRs, and I provide some examples on
      how these data can be interpreted to study basic principles of protein structure,
      to compare homologous proteins and to study mechanisms of receptor activation.
      Also, I show how in combination with the sequence analysis tools provided by the
      program GMoS, distortions in individual receptors can be put in the context of
      the whole Class A GPCR family. Specifically, quantification of the strong proline
      induced distortions in the transmembrane bundle of rhodopsin shows that they are
      not standard proline kinks. Moreover, the helix distortions in transmembrane
      helix (TMH) 5 and TMH 6 of rhodopsin are also present in the rest of GPCR crystal
      structures obtained so far, and thus, rhodopsin-based homology models have
      modeled correctly these strongly distorted helices. While in some cases the
      inherent "rhodopsin bias" of many of the GPCR models to date has not been a
      disadvantage, the availability of more templates will clearly result in better
      homology models. This type of analysis can be, of course, applied to any protein,
      and it may be particularly useful for the structural analysis of other membrane
      proteins. A detailed knowledge of the local structural changes related to ligand
      binding and how they are translated into larger-scale movements of transmembrane
      domains is key to understand receptor activation.

PMID- 22976032
TI  - Structure prediction of G protein-coupled receptors and their ensemble of
      functionally important conformations.
AB  - G protein-coupled receptors (GPCRs) are integral membrane proteins whose
      "pleiotropic" nature enables transmembrane (TM) signal transduction,
      amplification, and diversification via G protein-coupled and beta arrestin
      coupled pathways. GPCRs appear to enable this by being structurally flexible and
      by existing in different conformational states with potentially different
      signaling and functional consequences. We describe a method for the prediction of
      the three-dimensional structures of these different conformations of GPCRs
      starting from their amino acid sequence. It combines a unique protocol of
      computational methods that first predict the TM regions of these receptors and TM
      helix shapes based on those regions, which is followed by a locally complete
      sampling of TM helix packings and their scoring that results in a few (~10-20)
      lowest energy conformations likely to play a role in binding to different ligands
      and signaling events. Prediction of the structures for multiple conformations of
      a GPCR is starting to enable the testing of multiple hypotheses related to GPCR
      activation and binding to ligands with different signaling profiles.

PMID- 22976033
TI  - Target based virtual screening by docking into automatically generated GPCR
      models.
AB  - Target based virtual screening (VS) combined with high-throughput measurements is
      an extremely useful tool to identify small molecule hits for proteins and in
      particular for G-protein coupled receptors (GPCRs). However, this is a quite
      difficult process for GPCRs due to the paucity of 3D structural information on
      these receptors. Therefore, the only possibility for target based VS is to build
      a structural model of the GPCR to be used for docking. However, GPCR model
      building is a very time consuming process, if the model should be able to explain
      all experimental findings and this investment is not always justified, if the
      model is only used for VS. Thus, a fully automated workflow is presented here,
      where a large number of GPCR models is built, and the best model is identified to
      be used for docking. The workflow leads to moderate enrichments with a very low
      effort. The inputs required are the sequence of the targeted GPCR, a reference
      ligand with experimental information and a database of small molecules to be used
      for docking. Manual intervention is recommended at various points, but it is
      strictly speaking not necessary.

PMID- 22976034
TI  - Predicting the biological activities through QSAR analysis and docking-based
      scoring.
AB  - Numerous computational methodologies have been developed to facilitate the
      process of drug discovery. Broadly, they can be classified into ligand-based
      approaches, which are solely based on the calculation of the molecular properties
      of compounds, and structure-based approaches, which are based on the study of the
      interactions between compounds and their target proteins. This chapter deals with
      two major categories of ligand-based and structure-based methods for the
      prediction of biological activities of chemical compounds, namely quantitative
      structure-activity relationship (QSAR) analysis and docking-based scoring. QSAR
      methods are endowed with robustness and good ranking ability when applied to the
      prediction of the activity of closely related analogs; however, their great
      dependence on training sets significantly limits their applicability to the
      evaluation of diverse compounds. Instead, docking-based scoring, although not
      very effective in ranking active compounds on the basis of their affinities or
      potencies, offer the great advantage of not depending on training sets and have
      proven to be suitable tools for the distinction of active from inactive
      compounds, thus providing feasible platforms for virtual screening campaigns.
      Here, we describe the basic principles underlying the prediction of biological
      activities on the basis of QSAR and docking-based scoring, as well as a method to
      combine two or more individual predictions into a consensus model. Finally, we
      describe an example that illustrates the applicability of QSAR and molecular
      docking to G protein-coupled receptor (GPCR) projects.

PMID- 22976036
TI  - Modeling the structural communication in supramolecular complexes involving
      GPCRs.
AB  - This article describes a computational strategy aimed at studying the structural
      communication in G-Protein Coupled Receptors (GPCRs) and G proteins. The strategy
      relies on comparative Molecular Dynamics (MD) simulations and analyses of wild
      type (i.e., reference state) vs. mutated (i.e., perturbed state), or free (i.e.,
      reference state) vs. bound (i.e., perturbed state) forms of a GPCR or a G
      protein. Bound forms of a GPCR include complexes with small ligands and/or
      receptor dimers/oligomers, whereas bound forms of heterotrimeric GDP-bound G
      proteins concern the complex with a GPCR. The computational strategy includes
      structure prediction of a receptor monomer (in the absence of high-resolution
      structure), a receptor dimer/oligomer, and a receptor-G protein complex, which
      constitute the inputs of MD simulations. Finally, the analyses of the MD
      trajectories are instrumental in inferring the structural/dynamics differences
      between reference and perturbed states of a GPCR or a G protein. In this respect,
      focus will be put on the analysis of protein structure networks and communication
      paths.

PMID- 22976037
TI  - Exploring substrate diffusion in channels using biased molecular dynamics
      simulations.
AB  - Substrate transport and diffusion through membrane-bound channels are processes
      that can span a range of time scales, with only the fastest ones being amenable
      to most atomic-scale equilibrium molecular dynamics (MD) simulations. However,
      the application of forces within a simulation can greatly accelerate diffusion
      processes, revealing important structural and energetic features of the channel.
      Here, we demonstrate the use of two methods for applying biases to a substrate in
      a simulation, using the ammonia/ammonium transporter AmtB as an example. The
      first method, steered MD, applies a constant force or velocity constraint to the
      substrate, permitting the exploration of potential substrate pathways and the
      barriers encountered, although typically far outside of equilibrium. On the other
      hand, the second method, adaptive biasing forces, is quasi-equilibrium,
      permitting the derivation of a potential of mean force, which characterizes the
      free energy of the substrate during transport.

PMID- 22976035
TI  - Identification of motions in membrane proteins by elastic network models and
      their experimental validation.
AB  - Identifying the functional motions of membrane proteins is difficult because they
      range from large-scale collective dynamics to local small atomic fluctuations at
      different timescales that are difficult to measure experimentally due to the
      hydrophobic nature of these proteins. Elastic Network Models, and in particular
      their most widely used implementation, the Anisotropic Network Model (ANM), have
      proven to be useful computational methods in many recent applications to predict
      membrane protein dynamics. These models are based on the premise that
      biomolecules possess intrinsic mechanical characteristics uniquely defined by
      their particular architectures. In the ANM, interactions between residues in
      close proximity are represented by harmonic potentials with a uniform spring
      constant. The slow mode shapes generated by the ANM provide valuable information
      on the global dynamics of biomolecules that are relevant to their function. In
      its recent extension in the form of ANM-guided molecular dynamics (MD), this
      coarse-grained approach is augmented with atomic detail. The results from ANM and
      its extensions can be used to guide experiments and thus speedup the process of
      quantifying motions in membrane proteins. Testing the predictions can be
      accomplished through (a) direct observation of motions through studies of
      structure and biophysical probes, (b) perturbation of the motions by, e.g., cross
      linking or site-directed mutagenesis, and (c) by studying the effects of such
      perturbations on protein function, typically through ligand binding and activity
      assays. To illustrate the applicability of the combined computational ANM
      experimental testing framework to membrane proteins, we describe-alongside the
      general protocols-here the application of ANM to rhodopsin, a prototypical member
      of the pharmacologically relevant G-protein coupled receptor family.

PMID- 22976038
TI  - Methods to stabilize and destabilize ammonium borohydride.
AB  - Ammonium borohydride, NH(4)BH(4), has a high hydrogen content of rho(m) = 24.5
      wt% H(2) and releases 18 wt% H(2) below T = 160  degrees C. However, the half
      life of bulk NH(4)BH(4) at ambient temperatures and pressures, ~6 h, is
      insufficient for practical applications. The decomposition of NH(4)BH(4) (ABH(2))
      was studied at variable hydrogen and argon back pressures to investigate possible
      pressure mediated stabilization effects. The hydrogen release rate from solid
      ABH(2) at ambient temperatures is reduced by ~16% upon increasing the hydrogen
      back pressure from 5 to 54 bar. Similar results were obtained using argon
      pressure and the observed stabilization may be explained by a positive volume of
      activation, ca. 73 +/- 17 cc mol(-1), in the transition state leading to hydrogen
      release. Nanoconfinement in mesoporous silica, MCM-41, was investigated as
      alternative means to stabilize NH(4)BH(4). However, other factors appear to
      significantly destabilize NH(4)BH(4) and it rapidly decomposes at ambient
      temperatures into [(NH(3))(2)BH(2)][BH(4)] (DADB) in accordance with the bulk
      reaction scheme. The hydrogen desorption kinetics from nanoconfined
      [(NH(3))(2)BH(2)][BH(4)] is moderately enhanced as evidenced by a reduction in
      the DSC decomposition peak temperature of DeltaT = -13  degrees C as compared to
      the bulk material. Finally, we note a surprising result, storage of DADB at
      temperature <-30  degrees C transformed, reversibly, the [(NH(3))(2)BH(2)][BH(4)]
      into a new low temperature polymorph as revealed by both XRD and solid state MAS
      (11)B MAS NMR.

PMID- 22976039
TI  - Novel permittivity test for determination of yeast surface charge and
      flocculation abilities.
AB  - Yeast flocculation has been found to be important in many biotechnological
      processes. It has been suggested that flocculation is promoted by decreasing
      electrostatic repulsion between cells. In this study, we used an unconventional
      rapid technique--permittivity test--for determination of the flocculation
      properties and surface charge values of three industrial yeast strains with well
      known flocculation characteristics: Saccharomyces cerevisiae NCYC 1017 (brewery,
      ale), S. pastorianus NCYC 680 (brewery, lager), and Debaryomyces occidentalis
      LOCK 0251 (unconventional amylolytic yeast). The measurements of permittivity
      were compared with the results from two classical methods for determination of
      surface charge: Alcian blue retention and Sephadex DEAE attachment. The
      permittivity values for particular strains correlated directly with the results
      of Alcian blue retention (r = 0.9). The results also confirmed a strong negative
      relationship between the capacitance of yeast suspensions and their flocculation
      abilities. The highest permittivity was noted for the ale strain NCYC 1017, with
      weak flocculation abilities, and the lowest for the flocculating lager yeast NCYC
      680. This paper is the first to describe the possibility of using a rapid
      permittivity test to evaluate the surface charge of yeast cells and their
      flocculation abilities. This method is of practical value in various
      biotechnological industries where flocculation is applied as a major method of
      cell separation.

PMID- 22976040
TI  - 17beta-Estradiol inhibits outward voltage-gated K+ currents in human osteoblast
      like MG63 cells.
AB  - Previous studies have shown that 17beta-estradiol has a pivotal function by
      blocking voltage-gated K+ (Kv) channels in several different types of cells such
      as cardiac myocytes and neurons. Outward Kv currents can also be measured in
      osteoblasts, although little is known about the effects of 17beta-estradiol on
      these currents. In human osteoblast-like MG63 cells, we found that 17beta
      estradiol inhibits peak and end Kv currents, with IC50 values of 480 and 325 nM,
      respectively. To elucidate the mechanism of inhibition, the kinetics of Kv
      currents were investigated. The half-maximum activation potential (V(1/2)) was
      1.3 mV and was shifted left to -4.4 mV after application of 500 nM 17beta
      estradiol. For steady-state inactivation, the V(1/2) was -55.0 mV and weakly
      shifted left to -58.2 mV. To identify the molecular basis of outward Kv currents
      in MG63 cells, we performed RT-PCR analyses. The expression of Kv2.1 channels
      appeared to dominate over that of other Kv channels in MG63 cells. In COS-7 cells
      with heterologously expressed Kv2.1 channels, 17beta-estradiol also inhibits
      macroscopic currents of Kv2.1. Our data indicate that 17beta-estradiol inhibits
      Kv currents in human osteoblast-like MG63 cells and that Kv2.1 is a potential
      molecular correlate of outward Kv currents in these cells.

PMID- 22976042
TI  - The relationship between individual resource realization and sociodemographic and
      clinical characteristics in mentally ill patients.
AB  - OBJECTIVE: There has been a recent effort to investigate the role of individual
      resources in the field of mental health, but systematic research on this topic is
      lacking. The overall aim of the present study was the exploration of resource
      realization and other related variables in patients with mental disorders to
      provide basic knowledge on the upcoming field of psychotherapy research, which
      focuses on patients' strengths. METHOD: Current resource realization was assessed
      with a shortened form of the Resource Realization Questionnaire in a sample of
      332 inpatients with mental disorders. To explore the association between resource
      realization and related variables, group differences (t tests, analyses of
      variance) in gender, age, marital status, educational level, and type and number
      of diagnoses were calculated. The relationships between resource realization,
      symptom severity, interpersonal behavior, and therapeutic alliance were examined,
      and a regression tree analysis was calculated to establish relevant predictors of
      resource realization. RESULTS: There are several significant differences in
      current resource realization regarding marital status and number and type of
      diagnoses. A significant relationship between resource realization and symptom
      severity was found. The results regarding interpersonal behavior and therapeutic
      alliance were more heterogeneous. Symptom severity, gender, and chronic
      depression were found to be relevant predictors of resource realization.
      CONCLUSION: The close association between resource realization and symptom
      severity supports further investigation of the construct of resource realization
      within psychotherapy research.

PMID- 22976043
TI  - In memoriam: Dr Joseph Barnett Kirsner.

PMID- 22976045
TI  - Conditional pseudolikelihood methods for clustered ordinal, multinomial, or count
      outcomes with complex survey data.
AB  - In order to adjust individual-level covariate effects for confounding due to
      unmeasured neighborhood characteristics, we have recently developed conditional
      pseudolikelihood methods to estimate the parameters of a proportional odds model
      for clustered ordinal outcomes with complex survey data. The methods require
      sampling design joint probabilities for each within-neighborhood pair. In the
      present article, we develop a similar methodology for a baseline category logit
      model for clustered multinomial outcomes and for a loglinear model for clustered
      count outcomes. All of the estimators and asymptotic sampling distributions we
      present can be conveniently computed using standard logistic regression software
      for complex survey data, such as sas proc surveylogistic. We demonstrate validity
      of the methods theoretically and also empirically by using simulations. We apply
      the new method for clustered multinomial outcomes to data from the 2008 Florida
      Behavioral Risk Factor Surveillance System survey in order to investigate
      disparities in frequency of dental cleaning both unadjusted and adjusted for
      confounding by neighborhood.

PMID- 22976046
TI  - In situ electrochemical deposition and doping of C60 films applied to high
      performance inverted organic photovoltaics.
AB  - Novel C(60)-based cross-linked films formed by electrodeposition are produced and
      used as the electron-collection layer in inverted polymer solar cells (PSCs). The
      electrodeposited films exhibit a low work function of 4.2 eV and the PSCs perform
      well, with power conversion efficiencies of up to 6.31%. This new kind of
      electrodeposited film affords more opportunities to develop modified electrodes
      with a low work function.

PMID- 22976047
TI  - Sewage-exposed marine invertebrates: survival rates and microbiological
      accumulation.
AB  - A large number of bacteria, including agents responsible for diseases,
      characterise sewage-polluted seawaters. Apart from standards for bathing waters
      and bivalve aquaculture waters, there are no general microbiological standards
      applicable to seawaters to help decide if bacterial pollution is within
      acceptable ranges. This study represents an attempt towards the issue of
      comparing the susceptibility of different marine invertebrates subjected to
      polluted seawater with a high microbial contamination. We explored the survival
      rates and the microbiological accumulation of mollusc bivalves, echinoderms and
      crustaceans species exposed to sewage-polluted seawaters. Microbiological
      analyses were performed on the polluted seawater and on the homogenates of
      exposed and unexposed specimens. Culturable bacteria (22  degrees C and 37 
      degrees C) and microbial pollution indicators (total coliforms, Escherichia coli
      and intestinal enterococci) were measured. When exposed to the sewage-polluted
      seawater, the examined invertebrates showed different survival rates. In the
      filter feeders, bacterial densities at 22  degrees C and 37  degrees C rose after
      96 h of exposure to sewage. The highest concentrations of total coliforms and
      intestinal enterococci were found in exposed bivalve Mytilus galloprovincialis.
      The concentrations of bacteria growing at 37  degrees C were lower in the exposed
      deposit feeders compared to the polluted seawater. Some yeasts were absent in
      several exposed species although these yeasts were present in the polluted
      seawater. Our data suggest that the examined filter feeders, given their
      capability to survive and accumulate bacteria, may counteract the effects of
      sewage and restore seawater quality.

PMID- 22976048
TI  - Biochemical effects in crabs (Carcinus maenas) and contamination levels in the
      Bizerta Lagoon: an integrated approach in biomonitoring of marine complex
      pollution.
AB  - The biochemical effects in Carcinus maenas and contamination levels in seawater
      and sediments of Bizerta Lagoon (northeast of Tunisia) were investigated. The
      levels of metals and hydrocarbons were higher in seawater and sediments in Menzel
      Bourguiba and Cimentery in February and July than in the other sampling sites.
      Differences among sites for glutathione S-transferase, catalase,
      acetylcholinesterase activities, and the content of lipid peroxidation and
      metallothioneins in two important organs which accumulated contaminants (the
      gills and the digestive gland) of the C. maenas were found and possibly related
      to differences in metal and hydrocarbon levels. The seasonal variation of
      biomarkers was possibly associated with chemical contamination and also with the
      high fluctuation of physico-chemical characteristics of the sites. The integrated
      biomarker response values found in the five sites is in good agreement with
      hydrocarbon and trace metal concentrations detected in the water and sediments of
      the stressful places where crabs are living.

PMID- 22976050
TI  - Hepatitis B virus prevalence and vaccine response in HIV-infected children and
      adolescents on combination antiretroviral therapy in Kigali, Rwanda.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of hepatitis B
      virus (HBV) infection in a cohort of HIV-infected Rwandan children and
      adolescents on combination antiretroviral therapy (cART), and the success rate of
      HBV vaccination in those children found to be HBV negative. METHODS: HIV-infected
      children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count
      >=200 cells/mm and/or >=15% and without prior HBV vaccination (by history,
      vaccination cards and clinic records) underwent serologic testing for past
      (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen
      [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children
      with any positive HBV serologic tests were excluded from further vaccination; all
      others completed 3 HBV immunizations with 10 ug of ENGERIX-B. Anti-HBs titer was
      measured 4-6 weeks after the last immunization. RESULTS: Of 88 children, 6 (7%)
      children had active HBV infection and 8 (9%) had past HBV infection. The median
      (interquartile range) age, CD4 T-cell count and cART duration were 12.3 (10.1
      13.9) years, 626 (503 to 942) cells/mm and 1.9 (1.5-2.7) years, respectively.
      Seventeen children had detectable plasma HIV-1 RNA. Seventy-3 children completed
      3 immunizations with median (interquartile range) postimmunization anti-HBs
      concentration of 151 mIU/mL (1.03-650). Overall, 52 children (71%, 95% confidence
      interval: 61-82) developed a protective anti-HBs response. HIV-1 RNA and CD4 T
      cell count were independent predictors of a protective anti-HBs response.
      Protective anti-HBs response was achieved in 82% of children with undetectable
      HIV-1 RNA and 77% with CD4 T cells >=350/mm. CONCLUSIONS: The substantial HBV
      prevalence in this cohort suggests that HIV-infected Rwandan children should be
      screened for HBV before cART initiation. HIV viral suppression and CD4 T cells
      >=350/mm favored the likelihood of a protective response after HBV vaccination.

PMID- 22976049
TI  - Electrophysiological changes precede morphological changes to frontal cortical
      pyramidal neurons in the rTg4510 mouse model of progressive tauopathy.
AB  - Whole-cell patch-clamp recordings and high-resolution morphometry were used to
      assess functional and structural properties of layer 3 pyramidal neurons in early
      (<4 months) and advanced (>8 months) stages of tauopathy in frontal cortical
      slices prepared from rTg4510 tau mutant (P301L) mice. In early tauopathy,
      dendritic architecture is preserved. In advanced tauopathy, neurons can be
      categorized as either "atrophic" (58 %)-exhibiting marked atrophy of the apical
      tuft, or "intact" (42 %)-with normal apical tufts and, in some instances,
      proliferative sprouting of oblique branches of the apical trunk. Approximately
      equal numbers of atrophic and intact neurons contain neurofibrillary tangles
      (NFTs) or are tangle-free, lending further support to the idea that NFTs per se
      are not toxic. Spine density is decreased due to a specific reduction in mushroom
      spines, but filopodia are increased in both atrophic and intact neurons. By
      contrast to these morphological changes, which are robust only in the advanced
      stage, significant electrophysiological changes are present in the early stage
      and persist in the advanced stage in both atrophic and intact neurons. The most
      marked of these changes are: a depolarized resting membrane potential, an
      increased depolarizing sag potential and increased action potential firing rates
      all indicative of hyperexcitability. Spontaneous excitatory postsynaptic currents
      are not reduced in frequency or amplitude in either stage. The difference in the
      time course of functionally important electrophysiological changes versus
      regressive morphological changes implies differences in pathogenic mechanisms
      underlying functional and structural changes to neurons during progressive
      tauopathy.

PMID- 22976051
TI  - Staphylococcus aureus infections in pediatric oncology patients: high rates of
      antimicrobial resistance, antiseptic tolerance and complications.
AB  - BACKGROUND: : Patients with malignancies represent a population at high risk for
      drug-resistant infections. We sought to determine the clinical spectrum and
      molecular epidemiology of Staphylococcus aureus infections in pediatric oncology
      patients followed at Texas Children's Hospital (Houston, TX). Furthermore, we
      determined the prevalence of the chlorhexidine resistance gene qacA/B from
      isolates in this unique population. METHODS: : Patients with a history of
      malignancy and a culture-proven S. aureus infection were identified from 2001 to
      2011. Antibiotic susceptibility, pulsed-field gel electrophoresis and detection
      of qacA/B by polymerase chain reaction were performed on all isolates. Medical
      records for all patients were reviewed. RESULTS: : During the study period, 213
      isolates were identified from 179 patients with malignancies. Thirty-one percent
      of the isolates were methicillin-resistant S. aureus. The most common infectious
      diagnosis was bacteremia (85/213 [39.9%], with 72/85 [84.7%] being catheter
      associated). Thirteen patients with bacteremia were found to have pulmonary
      nodules at the time of presentation; only S. aureus was found in tissue in 5 of
      the 6 patients who underwent lung biopsy. After 2007, 18.2% of isolates were
      qacA/B positive with a steady increase in prevalence every year (chi for trend P
      = 0.04). CONCLUSIONS: : S. aureus is a significant cause of morbidity and
      mortality in pediatric oncology patients at Texas Children's Hospital. In
      addition to the more well-known clinical manifestations, this pathogen can also
      be associated with pulmonary nodules. Furthermore, the prevalence of S. aureus
      isolates carrying antiseptic resistance genes increased in this population.
      Additional clinical and molecular studies and surveillance among pediatric
      oncology patients are warranted to further explore these findings.

PMID- 22976052
TI  - Seroreversion of treponemal tests in infants meeting canadian surveillance
      criteria for confirmed early congenital syphilis.
AB  - BACKGROUND: Few data exist on the serologic outcome of treponemal tests in
      congenital syphilis. METHODS: A chart review was conducted on all confirmed early
      congenital syphilis cases in Edmonton, Canada, from 2005-2010. RESULTS: Of the 16
      cases identified, 11 (69%) infants seroreverted their treponemal tests by 18
      months. Cases that did not serorevert their treponemal tests were statistically
      more likely to have delayed treatment and to have higher maternal rapid plasma
      reagin titers at birth. CONCLUSIONS: Our data suggest that the majority of early
      congenital syphilis cases will serorevert their treponemal tests by 18 months.

PMID- 22976053
TI  - Identification of a novel bone morphogenetic protein (BMP)-inducible transcript,
      BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in
      the Id genes.
AB  - Bone morphogenetic proteins (BMPs) inhibit myogenesis and induce osteoblastic
      differentiation in myoblasts. They also induce the transcription of several
      common genes, such as Id1, Id2 and Id3, in various cell types. We have reported
      that a GC-rich element in the Id1 gene functions as a BMP-responsive element
      (BRE) that is regulated by Smads. In this study, we analyzed and identified BREs
      in the 5'-flanking regions of the mouse Id2 and Id3 genes. The core GGCGCC
      sequence was conserved among the BREs in the Id1, Id2 and Id3 genes and was
      essential for the response to BMP signaling via Smads. We found a novel BRE on
      mouse chromosome 13 at position 47,723,740-47,723,768 by searching for conserved
      sequences containing the Id1 BRE. This potential BRE was found in the 5'-flanking
      region of a novel gene that produces a non-coding transcript, termed BMP
      inducible transcript-1 (BIT-1), and this element regulated the expression of this
      gene in response to BMP signaling. We found that BIT-1 is expressed in BMP target
      tissues such as the testis, brain, kidney and cartilage. These findings suggest
      that the transcriptional induction of the Ids, BIT-1 and additional novel genes
      containing the conserved BRE sequence may play an important role in the
      regulation of the differentiation and/or function of target cells in response to
      BMPs.

PMID- 22976054
TI  - Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on
      manifestations in the skeletal system and literature review.
AB  - Osteomalacia is a metabolic bone disease that leads to softening of the bones and
      can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir
      dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading
      to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose
      adefovir-induced hypophosphatemic osteomalacia that initially presented with
      diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2
      year history of bone pain involving the dorsal mid-thorax, lower anterior chest
      wall, right sacroiliac joint area, and both knees. The patient had been receiving
      adefovir for 5 years before confirmation of hypophosphatemia and urinary
      phosphate wasting. Bone scintigraphy revealed multifocal lesions including
      multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both
      posterior iliac bones, both proximal tibia, right calcaneus, and the left second
      metatarsophalangeal joint area, which were suggestive of metabolic bone disorder.
      Bone pain was significantly reduced within 3 months after supplementation with
      phosphate and calcitriol. The second patient was a 54-year-old male who presented
      with an 18-month history of severe bone pain of the right medial knee and low
      back. The patient had been taking adefovir for approximately 40 months before the
      development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D
      deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum,
      both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of
      the right proximal femur, right proximal tibia, and the left lateral tarsal bone.
      The symptoms improved by changing the antiviral agent from adefovir to entecavir.
      Because osteomalacia often presents with diffuse bone pain, non-specific
      radiologic findings and non-characteristic routine serum biochemical changes, the
      disease can be confused with various musculoskeletal diseases and a high index of
      suspicion is necessary for an early diagnosis in patients receiving adefovir
      therapy.

PMID- 22976057
TI  - Neurophilia: a fascination for neurology--a new syndrome.

PMID- 22976055
TI  - The novel p53-dependent metastatic and apoptotic pathway induced by vitexin in
      human oral cancer OC2 cells.
AB  - Vitexin, identified as apigenin-8-C-D-glucopyranoside, a natural flavonoid
      compound found in certain herbs such as hawthorn herb, has been reported to
      exhibit anti-oxidative, anti-inflammatory, anti-metastatic and antitumor
      properties. The aim of this study was to investigate the possible existence of
      p53-dependent pathway underlying vitexin-induced metastasis and apoptosis in
      human oral cancer cells, OC2 cells. Vitexin decreased cell viability
      significantly. Meanwhile, the expression of tumor suppressor p53 and a small
      group of its downstream genes, p21(WAF1) and Bax, were upregulated. The p53
      inhibitor pifithrin-alpha (PFT-alpha) knockdown of the signaling of p53 led
      vitexin to lose its antitumor effect and inhibited the expression of p53
      downstream genes, p2(WAF1) and Bax. Vitexin had anti-metastatic potential
      accompanied with increasing plasminogen activator inhibitor 1 (PAI-1)
      accumulation and decreasing matrix metalloproteinase-2 expression. Our present
      study evidenced, by using p53 inhibitor PFT-alpha, PAI-1 and peroxisome
      proliferator-activated receptor gamma are downstream genes of p53 in vitexin
      induced signaling. MAPK inhibitor PD98059 decreased the OC2 cells viability
      significantly. The expression of p53 and its downstream genes p21(WAF1) and Bax
      were enhanced by blocking the activation of p42/p44 MAPK in response to treatment
      with vitexin. Moreover, p42/p44 MAPK played a negative role in p53-dependent
      metastasis and apoptosis. We give evidence for the first time that the novel p53
      dependent metastatic and apoptotic pathway induced by vitexin in human oral
      cancer OC2 cells.

PMID- 22976059
TI  - Spasticity: pathophysiology, evaluation and management.
AB  - Spasticity is common in many neurological disorders, such as stroke and multiple
      sclerosis. It is part of the upper motor neurone syndrome manifesting as
      increased tone, clonus, spasms, spastic dystonia and co-contractions. The impact
      of spasticity varies from it being a subtle neurological sign to severe
      spasticity causing pain and contractures. Existing spasticity can be worsened by
      external factors such as constipation, urinary tract infections or pressure
      ulcers. Its management involves identification and elimination of triggers;
      neurophysiotherapy; oral medications such as baclofen, tizanidine and dantrolene;
      focal injection of botulinum toxin, alcohol or phenol, or baclofen delivered
      intrathecally through a pump; and surgical resection of selected dorsal roots of
      the spinal cord. This article reviews the current understanding of
      pathophysiology, clinical features and management of spasticity.

PMID- 22976058
TI  - The genetics of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system. Improved prevention and treatment will depend on a greater
      understanding of the causes and mechanisms involved in its onset and progression.
      MS is clearly driven by both environmental and genetic factors. Established
      contributory environmental factors include lower ultraviolet radiation exposure
      and lower vitamin D levels, Epstein-Barr virus and smoking. Our current
      understanding of MS genetics is undergoing a major upgrade as new genetic
      technologies are applied to large MS studies. In this article, we review the
      current literature describing a genetic contribution to MS susceptibility and
      review the methods to detect genetic variants that may underlie the genetic
      contribution to MS. We also consider how reporting of genetic discoveries in MS
      in the lay press has caused some confusion among patients and their families,
      who, not surprisingly, think that these discoveries can be translated into an
      available genetic test to diagnose MS or recognise family members at risk of
      developing MS. We review the current limited clinical use of genetics in the
      diagnosis and management of MS.

PMID- 22976060
TI  - Epilepsy: mimics, borderland and chameleons.
AB  - Epilepsy mimics such as syncope and psychogenic attacks, can present like
      epilepsy, and can be erroneously managed as epilepsy. There are also several
      conditions at the borderland that closely relate to epilepsy yet are probably
      separate from it, eg. migralepsy and parasomnia. Finally, there are times when
      epileptic seizures resemble one of the epilepsy mimics. This is epilepsy in
      disguise-the epilepsy chameleons. Seizures with typically unusual manifestations,
      such as occipital or parietal lobe seizures, or those occurring in situations
      where another cause seems more likely, eg, in a person with alcoholism, may well
      be overlooked as epilepsy and initially escape diagnosis. This review explores
      the mimics of adult epilepsy, the epilepsy borderland, and focuses particularly
      on epilepsy chameleons.

PMID- 22976061
TI  - Normal anatomy of the base of the skull, orbit, pituitary and cranial nerves.

PMID- 22976062
TI  - Histiocytosis for the neurologist: a case of Erdheim-Chester disease.
AB  - The histiocytoses are a rare but diverse group of disorders, ranging from
      localised, self-limiting lesions to disseminated, fulminant, multi-system
      disease. Some histiocytoses may cause or present with neurological disease and
      their recognition can be challenging. We illustrate this with a case, followed by
      a discussion of the clinical characteristics and management of the more common
      histiocytoses that may present to the neurologist.

PMID- 22976063
TI  - Hypereosinophilia and acute bilateral facial palsy: an unusual presentation of a
      common disease.
AB  - A 60-year-old man presented with an acute, pruritic, erythematous rash associated
      with marked hypereosinophilia (2.34*10(9)/l (0.04-0.40)). There was eosinophilic
      infiltration on hepatic, bone marrow and lymph node biopsies, with multiple lung
      nodules and mild splenomegaly. However, extensive investigation excluded
      parasitic or bacterial causes, specific allergens or the Fip1L1 mutation seen in
      myeloproliferative hypereosinophilia. Six months into the illness, he developed
      an acute, left, complete lower motor neurone facial palsy over hours, and an
      acute right lower motor neurone facial palsy 2&emsp14;weeks later, without
      recovery. Over the subsequent 3&emsp14;months, he developed complex partial
      seizures, a transient 72-h non-epileptic encephalopathy and episodic vertigo with
      ataxia. Further investigation showed bilateral enhancement of the VII nerves and
      labyrinthis on gadolinium-enhanced MR brain scan, cerebrospinal fluid
      lymphocytosis and neurophysiological evidence of polyradicolopathy. His
      eosinophil count fell with corticosteroids, hydroxycarbamide, imatinib and
      ultimately mepolezumab, but without symptomatic improvement. Repeat lymph node
      biopsy showed Kaposi's sarcoma, leading to a diagnosis of HIV-1 infection with a
      modestly reduced CD4 count of 413*10(6)/l (430-1690). Hypereosinophila and
      eosinophilic folliculitis are recognised features of advanced HIV infection, and
      transient bilateral facial palsy occasionally occurs at the time of
      seroconversion. This is the first report of a chronic bilateral facial palsy
      likely due to primary HIV infection, not occurring during seroconversion and in
      association with hypereosinophilia. This case emphasises the protean
      manifestations of HIV infection and the need for routine testing in atypical
      clinical presentations.

PMID- 22976064
TI  - Acute flaccid paralysis with chronic cough.

PMID- 22976065
TI  - A neurological letter from West Yorkshire.

PMID- 22976066
TI  - Prescribing in Parkinson's disease: a story of hope and adverse events.
AB  - A review of National Health Service spending in England on prescription drugs
      used in Parkinsonism over the last 10 years shows that spending has risen rapidly
      and that newly introduced drugs are quickly and expensively adopted. This paper
      explores the gains and costs of such prescribing.

PMID- 22976067
TI  - Trigeminal trophic syndrome.

PMID- 22976069
TI  - Oh, it is just a case report.

PMID- 22976070
TI  - Inflammatory proteins and the severity of dilated Virchow-Robin Spaces in the
      elderly.
AB  - Recent studies suggest dilated Virchow-Robin Spaces (dVRS) could be a
      manifestation of cerebral small-vessel disease, but little is known about their
      risk factors. As inflammation has been associated with other brain MRI findings,
      we investigated whether interleukin-6 and C-reactive protein were associated with
      the severity of dVRS in the eldery. dVRS were assessed in basal ganglia and white
      matter and rated on a severity scale. We found that elevated interleukin-6 levels
      were associated with higher severity of dVRS in basal ganglia, suggesting that
      inflammation might be associated with the burden of dVRS in the elderly.

PMID- 22976071
TI  - Dementia specialists and early adoption of amyloid imaging.
AB  - The goal of this study was to describe the attitudes of U.S. neurologists
      specializing in dementia toward the use of amyloid imaging in the diagnosis of
      Alzheimer's disease (AD). A cross-sectional electronic physician survey of
      dementia specialists at U.S. medical schools was performed. The response rate for
      the survey was 51.9% (135/260). Greater than 83% of respondents plan to use
      amyloid imaging to evaluate patients for AD. Most respondents intend to use
      amyloid imaging as an adjunctive diagnostic modality to confirm (77%) or rule-out
      (73%) a diagnosis of AD; 24% plan to use amyloid imaging to screen asymptomatic
      individuals for evidence of cerebral amyloid. Specialists who do not intend to
      use amyloid imaging (16%) express concern about the cost (73%), the usefulness
      (55%), and likelihood of patient (55%) and clinician (59%) misinterpretation of
      findings. The need for patient pre-test counseling was endorsed by a large
      percentage (92%) of dementia specialists (higher than for genetic testing (82%)).
      In conclusion, dementia specialists, particularly young specialists, are likely
      to be early adopters of amyloid imaging. Assuming ready availability, this new
      technology would be used as a confirmatory test in the evaluation of AD, as well
      as a screening tool for asymptomatic pathology. Specialists recognize the
      complexity of interpreting amyloid imaging findings and the need for patient
      counseling before undergoing testing.

PMID- 22976072
TI  - Silicon-rich mineral water as a non-invasive test of the 'aluminum hypothesis' in
      Alzheimer's disease.
AB  - There has been a plausible link between human exposure to aluminum and
      Alzheimer's disease for several decades. We contend that the only direct and
      ethically acceptable experimental test of the 'aluminum hypothesis', which would
      provide unequivocal data specific to the link, is to test the null hypothesis
      that a reduction in the body burden of aluminum to its lowest practical limit
      would have no influence upon the incidence, progression, or severity of
      Alzheimer's disease. Herein we are testing the hypothesis that silicon-rich
      mineral waters can be used as non-invasive methods to reduce the body burden of
      aluminum in individuals with Alzheimer's disease and a control group consisting
      of their carers and partners. We have shown that drinking up to 1 L of a silicon
      rich mineral water each day for 12 weeks facilitated the removal of aluminum via
      the urine in both patient and control groups without any concomitant affect upon
      the urinary excretion of the essential metals, iron and copper. We have provided
      preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the
      body burden of aluminum fell in individuals with Alzheimer's disease and,
      concomitantly, cognitive performance showed clinically relevant improvements in
      at least 3 out of 15 individuals. This is a first step in a much needed rigorous
      test of the 'aluminum hypothesis of Alzheimer's disease' and a longer term study
      involving many more individuals is now warranted.

PMID- 22976073
TI  - Methods for measuring tau pathology in transgenic mouse models.
AB  - In Alzheimer's disease (AD) and tauopathies, tau becomes hyperphosphorylated,
      undergoes a conformational change, and becomes aggregated and insoluble. There
      are three methods commonly used to study the insoluble tau fraction, two that
      utilize detergents (Sarkosyl and RIPA) and another that does not (insoluble).
      However, these methods require large amounts of homogenate for a relatively low
      yield of the insoluble fraction, which can be problematic when dealing with small
      tissue samples. Furthermore, the most common way of analyzing this material is
      through densitometry of immunoblots, offering only semiquantitative measurements.
      We provide a comparison of the three methods commonly used (Sarksoyl, RIPA, and
      insoluble) through immunoblot and ELISA analyses. Finally, we tested a new method
      to determine aggregated tau levels, utilizing a monoantibody tau ELISA. The
      insoluble fractions of four different mouse models (P301 L, htau, wild type, and
      knockout) as well as human AD and control brains were examined. There were
      significant correlations between the three insoluble methods for both total tau
      and pS396/404 tau measured by immunoblot or ELISA analyses. Additionally, the
      results from the ELISA method correlated significantly with those from immunoblot
      analyses. Finally, the monoantibody assay on the lysate significantly correlated
      with the total tau ELISAs performed on the three insoluble preparations. Taken
      together, these results suggest that all three insoluble preparation methods
      offer similar results for measuring insoluble tau in either mouse or human
      brains. In addition the new monoantibody ELISA offers a simple quantitative
      method to measure the amount of aggregated tau in both human and mouse brains.

PMID- 22976074
TI  - Plasma amyloid-beta levels and prognosis in incident dementia cases of the 3-City
      Study.
AB  - Studies of plasma amyloid-beta (Abeta) levels as potential biomarkers for
      incident Alzheimer's disease (AD) have yielded contradictory results. We explored
      the associations between plasma Abeta(40), Abeta(42), and truncated Abeta levels,
      and prognosis of dementia in participants of the prospective 3-City Study. 120
      aged individuals diagnosed with 2-year incident dementia were followed up for
      seven years. The associations between Abeta plasma levels and baseline cognitive
      score, cognitive decline, and death were examined. A higher level of baseline
      plasma Abeta was associated with worse cognitive status two years prior to
      incident dementia diagnosis. In incident AD patients, the association was only
      significant for Abeta(40) and Abeta(n-42). In the fast cognitive decliners group,
      especially in AD cases, a higher level of 5 pg/ml of baseline Abeta(42), Abeta(n
      42), Abeta(n-42)/Abeta(n-40), and Abeta(42)/Abeta(40) ratios were associated with
      a lower risk of fast cognitive decline based on the Isaacs Set Test score. There
      was no association between peptide levels and mortality in demented subjects.
      When assayed at prodromal stage, plasma Abeta levels may be potentially useful
      markers of fast cognitive decline in individuals who subsequently become
      demented.

PMID- 22976076
TI  - Characterization of Mexican Americans with mild cognitive impairment and
      Alzheimer's disease.
AB  - The purpose of the study was to provide characterization of Mexican Americans who
      meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI).
      For the study, 1,069 participants ages 40 and above who self-identified as either
      non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a
      community-based participatory research approach. Global cognition was assessed
      via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical
      Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item
      version. Age, gender, education, ApoE epsilon4 allele frequency, and diabetic
      diagnoses were also analyzed. The findings showed that Mexican Americans (normal
      controls, MCI, and AD) were younger, less highly educated, performed more poorly
      on the MMSE, endorsed more symptoms of depression, were more likely to be
      diagnosed with diabetes, and possessed the ApoE epsilon4 allele less frequently.
      Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among
      Mexican Americans (OR = 1.06, 95% CI = 1.03-1.09). Age (B = 0.07, std = 0.02, p <
      0.001) and ApoE epsilon4 presence (B = 0.9, std = 0.4, p = 0.02) were
      significantly related to increased disease severity. Given the rapidly growing
      and aging Mexican American population, there is a substantial need for research
      into cognitive aging, MCI, and AD among this ethnic group. The current findings
      hold important implications for both clinic and research settings and point to
      additional research needs.

PMID- 22976075
TI  - MRI signatures of brain macrostructural atrophy and microstructural degradation
      in frontotemporal lobar degeneration subtypes.
AB  - Brain magnetic resonance imaging (MRI) studies have demonstrated regional
      patterns of brain macrostructural atrophy and white matter microstructural
      alterations separately in the three major subtypes of frontotemporal lobar
      degeneration (FTLD), which includes behavioral variant frontotemporal dementia
      (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This
      study was to investigate to what extent the pattern of white matter
      microstructural alterations in FTLD subtypes mirrors the pattern of brain
      atrophy, and to compare the ability of various diffusion tensor imaging (DTI)
      indices in characterizing FTLD patients, as well as to determine whether DTI
      measures provide greater classification power for FTLD than measuring brain
      atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with
      PNFA) and 19 healthy age-matched control subjects underwent both structural MRI
      and DTI scans. Measurements of regional brain atrophy were based on T1-weighted
      MRI data and voxel-based morphometry. Measurements of regional white matter
      degradation were based on voxelwise as well as regions-of-interest tests of DTI
      variations, expressed as fractional anisotropy, axial diffusivity, and radial
      diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited
      characteristic regional patterns of brain atrophy and white matter damage. DTI
      overall provided significantly greater accuracy for FTLD classification than
      brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white
      matter damage in FTLD than other DTI indices. The findings suggest that DTI in
      general and radial diffusivity in particular are more powerful measures for the
      classification of FTLD patients from controls than brain atrophy.

PMID- 22976077
TI  - The effect of an aloe polymannose multinutrient complex on cognitive and immune
      functioning in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a leading killer of Americans, imparts a significant
      toll on the quality of life of the patient and primary caregiver, and results in
      inordinate costs in an already overburdened medical system. Prior studies on
      cholinesterase inhibitors among AD patients have shown minimal amelioration of
      disease symptoms and/or restoration of lost cognitive functioning. The effect of
      improved nutrition, particularly with dietary supplements, on cognitive
      functioning may offer an alternative strategy compared to standard treatment. The
      present pilot study investigated the effect of an aloe polymannose multinutrient
      complex (APMC) formula on cognitive and immune functioning over 12 months among
      adults diagnosed with AD. Subjects participated in an open-label trial and
      consumed 4 teaspoons per day of the APMC. The ADAS-cog, MMSE, ADCS-ADL, and SIB
      were administered at baseline and 3, 6, 9, and 12 months follow-up. Cytokines and
      lymphocyte and monocyte subsets were assessed at baseline and 12 months. The mean
      ADAS-cog cognition score significantly improved at 9 and 12 months from baseline,
      and 46% of our sample showed clinically-significant improvement (>=4-point
      change) from baseline to 12 months. Participants showed significant decreases in
      tumor necrosis factor-alpha, vascular endothelial growth factor, and interleukins
      2 and-4. CD90+, CD95+CD3+, CD95+CD34+, CD95+CD90+, CD14+CD34+, CD14+CD90+, and
      CD14+CD95+ decreased significantly, whereas CD14+ significantly increased.
      Participants tolerated the APMC supplement with few, temporary adverse reactions.
      Our results showed improvements in both clinical and physiological outcomes for a
      disease that otherwise has no standard ameliorative remedy.

PMID- 22976079
TI  - Synthesis and characterisation of cobalt(II) phosphonate cage complexes utilizing
      carboxylates and pyridonates as co-ligands.
AB  - The synthesis and structures of fifteen new cobalt complexes containing
      phosphonate ligands are reported. The compounds also utilize carboxylates and 6
      chloro-2-pyridonate (chp) as co-ligands. The majority of the compounds are
      decametallic: [Co(10)(chp)(12)(O(3)PPh)(2)(O(2)CPh)(4)(H(2)O)(4)],
      [Co(10)(chp)(12)(O(3)PPh)(2)(O(2)C(t)Bu)(4)(H(2)O)(4)],
      [Co(10)(chp)(12)(O(3)PPh)(2)(O(2)CPh(t)Bu)(4)(H(2)O)(4)],
      [Co(10)(chp)(6)(O(3)PCH(2)Ph)(2)(O(2)CPh)(8)(F)(2) (H(2)O)(2)(EtOAc)(2)],
      [Co(10)(chp)(8)(O(3)PCH(2)Ph)(2)(O(2)CPh)(8)(F)(2)(MeCN)(2)](HNEt(3))(2),
      [Co(10)(chp)(6)(O(3)PCH(2)Ph)(2)(O(2)C(t)Bu)(8)(F)(2)(H(2)O)(2)(MeCOMe)(2)],
      [Co(10)(chp)(6)(O(3)PMe)(2) (O(2)C(t)Bu)(8)(F)(2)(MeCN)(4)],
      [Co(10)(chp)(6)(O(3)PEt)(2)(O(2)CPh)(8)(F)(2)(MeCN)(4)],
      [Co(10)(chp)(6)(O(3)POct)(2)(O(2)CPh)(8)(F)(2)(MeCN)(4)],
      [Co(10)(chp)(8)(Hchp)(2)(O(3)PCH(2)Nap) (O(2)CPh)(7)(OH)(3)(H(2)O)],
      [Co(10)(chp)(12)(O(3)PPh)(2)(O(2)CPh-2-Ph)(4)(H(2)O)(4)] and
      [Co(10)(chp)(12)(O(3)PMe)(2)(O(2)CPh-2-Ph)(4)(H(2)O)(4)]. Two nine-metal cages
      and one hexametallic cage are also reported:
      [Co(9)(chp)(9)(O(3)P(t)Bu)(O(2)C(t)Bu)(6)(OH)],
      [Co(9)(chp)(7)(O(3)PCH(2)Ph)(2)(O(3)PCH(2)Ph)(O(2)CCPh(3))(5)(OH)(H(2)O)(2)(MeCN)
      and [Co(6)(chp)(6)(Hchp)(2)(O(3)P(t)Bu)(O(2)CPh-2
      Ph)(3)(F)(H(2)O)](HNEt(3))(Cl). Magnetic studies show predominantly anti
      ferromagnetic exchange interactions between the cobalt(ii) sites, with
      diamagnetic ground states for most of the compounds studied.

PMID- 22976080
TI  - VarB: a variation browsing and analysis tool for variants derived from next
      generation sequencing data.
AB  - SUMMARY: There is an immediate need for tools to both analyse and visualize in
      real-time single-nucleotide polymorphisms, insertions and deletions, and other
      structural variants from new sequence file formats. We have developed VarB
      software that can be used to visualize variant call format files in real time, as
      well as identify regions under balancing selection and informative markers to
      differentiate user-defined groups (e.g. populations). We demonstrate its utility
      using sequence data from 50 Plasmodium falciparum isolates comprising two
      different continents and confirm known signals from genomic regions that contain
      important antigenic and anti-malarial drug-resistance genes. AVAILABILITY AND
      IMPLEMENTATION: The C++-based software VarB and user manual are available from
      www.pathogenseq.org/varb. CONTACT: taane.clark@lshtm.ac.uk

PMID- 22976078
TI  - 3xTg-AD mice exhibit an activated central stress axis during early-stage
      pathology.
AB  - Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to
      the organism's innate need for homeostasis. The glucocorticoids (GCs) that are
      released into the circulation upon acute activation of the HPA axis perform
      stress-adaptive functions and provide negative feedback to turn off the HPA axis,
      but can be detrimental when in excess. Long-term activation of the HPA axis (such
      as with chronic stress) enhances susceptibility to neuronal dysfunction and
      death, and increases vulnerability to Alzheimer's disease (AD). However, little
      is known how components of the HPA axis, upstream of GCs, impact vulnerability to
      AD. This study examined basal gene expression of stress-related molecules in
      brains of 3xTg-AD mice during early-stage pathology. Basal GC levels and mRNA
      expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR),
      and corticotropic releasing hormone (CRH) in several stress- and emotionality
      related brain regions were measured in 3-4-month-old 3xTg-AD mice. Despite normal
      GC levels, young 3xTg-AD mice exhibit an activated central HPA axis, with altered
      mRNA levels of MR and GR in the hippocampus, GR and CRH in the paraventricular
      nucleus of the hypothalamus, GR and CRH in the central nucleus of the amygdala,
      and CRH in the bed nucleus of the stria terminalis. This HPA axis activation is
      present during early-stage neuropathology when 3xTg-AD mice show mild behavioral
      changes, suggesting an ongoing neuroendocrine regulation that precedes the onset
      of severe AD-like pathology and behavioral deficits.

PMID- 22976081
TI  - Phylogenetics, likelihood, evolution and complexity.
AB  - SUMMARY: Phylogenetics, likelihood, evolution and complexity (PLEX) is a flexible
      and fast Bayesian Markov chain Monte Carlo software program for large-scale
      analysis of nucleotide and amino acid data using complex evolutionary models in a
      phylogenetic framework. The program gains large speed improvements over standard
      approaches by implementing 'partial sampling of substitution histories', a data
      augmentation approach that can reduce data analysis times from months to minutes
      on large comparative datasets. A variety of nucleotide and amino acid
      substitution models are currently implemented, including non-reversible and site
      heterogeneous mixture models. Due to efficient algorithms that scale well with
      data size and model complexity, PLEX can be used to make inferences from hundreds
      to thousands of taxa in only minutes on a desktop computer. It also performs
      probabilistic ancestral sequence reconstruction. Future versions will support
      detection of co-evolutionary interactions between sites, probabilistic tests of
      convergent evolution and rigorous testing of evolutionary hypotheses in a
      Bayesian framework. AVAILABILITY AND IMPLEMENTATION: PLEX v1.0 is licensed under
      GPL. Source code and documentation will be available for download at
      www.evolutionarygenomics.com/ProgramsData/PLEX. PLEX is implemented in C++ and
      supported on Linux, Mac OS X and other platforms supporting standard C++
      compilers. Example data, control files, documentation and accessory Perl scripts
      are available from the website. CONTACT: David.Pollock@UCDenver.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22976082
TI  - An RNA Mapping DataBase for curating RNA structure mapping experiments.
AB  - SUMMARY: We have established an RNA mapping database (RMDB) to enable structural,
      thermodynamic and kinetic comparisons across single-nucleotide-resolution RNA
      structure mapping experiments. The volume of structure mapping data has greatly
      increased since the development of high-throughput sequencing techniques,
      accelerated software pipelines and large-scale mutagenesis. For scientists
      wishing to infer relationships between RNA sequence/structure and these mapping
      data, there is a need for a database that is curated, tagged with error estimates
      and interfaced with tools for sharing, visualization, search and meta-analysis.
      Through its on-line front-end, the RMDB allows users to explore single-nucleotide
      resolution mapping data in heat-map, bar-graph and colored secondary structure
      graphics; to leverage these data to generate secondary structure hypotheses; and
      to download the data in standardized and computer-friendly files, including the
      RDAT and community-consensus SNRNASM formats. At the time of writing, the
      database houses 53 entries, describing more than 2848 experiments of 1098 RNA
      constructs in several solution conditions and is growing rapidly. AVAILABILITY:
      Freely available on the web at http://rmdb.stanford.edu. CONTACT:
      rhiju@stanford.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics Online.

PMID- 22976083
TI  - Extra-binomial variation approach for analysis of pooled DNA sequencing data.
AB  - MOTIVATION: The invention of next-generation sequencing technology has made it
      possible to study the rare variants that are more likely to pinpoint causal
      disease genes. To make such experiments financially viable, DNA samples from
      several subjects are often pooled before sequencing. This induces large between
      pool variation which, together with other sources of experimental error, creates
      over-dispersed data. Statistical analysis of pooled sequencing data needs to
      appropriately model this additional variance to avoid inflating the false
      positive rate. RESULTS: We propose a new statistical method based on an extra
      binomial model to address the over-dispersion and apply it to pooled case-control
      data. We demonstrate that our model provides a better fit to the data than either
      a standard binomial model or a traditional extra-binomial model proposed by
      Williams and can analyse both rare and common variants with lower or more
      variable pool depths compared to the other methods. AVAILABILITY: Package
      'extraBinomial' is on http://cran.r-project.org/. CONTACT:
      chris.wallace@cimr.cam.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics Online.

PMID- 22976084
TI  - Press pause before send: a case in point.
AB  - There are many ways in which our digital era is influencing development. There is
      greater difficulty in delaying gratification, interference in the growth of the
      capacity for empathy, more trouble in developing the ability to relate face-to
      face, and overuse of two-dimensional communication. All of these have
      implications for clinical work. This article presents a case in point, and some
      suggestions for ways to attempt to address these difficulties. It is suggested
      that the clinical situation itself is uniquely valuable as an antidote to the
      problems posed by the technological world of today.

PMID- 22976085
TI  - An overview of CE in clinical analysis.
AB  - The development and general applications of capillary electrophoresis (CE) in the
      field of clinical chemistry are discussed. It is shown how the early development
      of electrophoresis was closely linked to clinical testing. The rise of gel
      electrophoresis in clinical chemistry is described, as well as the eventual
      developments that lead to the creation and the use of modern CE. The general
      principles of CE are reviewed and the potential advantages of this method in
      clinical testing are examined. Finally, an overview is presented of several areas
      in which CE is now being developed for use with clinical samples.

PMID- 22976086
TI  - Monitoring of arrays of amino acids in clinical samples using capillary
      electrophoresis with contactless conductivity detection.
AB  - Capillary electrophoresis (CE) with contactless conductivity detection (C(4)D) is
      readily applicable to determinations of amino acids in clinical samples. Most of
      these analyses employ long separation pathways. This chapter describes CE/C(4)D
      determinations of 28 biogenic amino acids in a short capillary with an effective
      length of 18 cm. All the test amino acids can be mutually separated in
      electrolytes of 0.5-10 mol/L acetic acid. The time of analysis does not exceed 6
      min; the limits of detection vary from 0.1 to 1.7 MUmol/L for all the analytes.
      The pretreatment of the biological material is very simple, consisting of the
      removal of proteins by an addition of acetonitrile and subsequent filtration. The
      procedure has been successfully applied to determinations of the whole amino acid
      spectra in blood plasma, urine, saliva, cerebrospinal, and amniotic fluid
      samples.

PMID- 22976087
TI  - The selective determination of sulfates, sulfonates, and phosphates in urine by
      capillary electrophoresis/mass spectrometry.
AB  - Metabolite identification and metabolite profiling are of major importance in the
      pharmaceutical and clinical context. However, anions of biological relevance such
      as sulfates, sulfonates, and phosphates are rarely included in common techniques
      for metabolite studies. In this protocol, we demonstrate a unique method to
      selectively determine these anions. The method comprises a capillary
      electrophoresis separation using an acidic background electrolyte (pH <= 2) and
      anodic detection by mass spectrometry via negative electrospray ionization. In
      this way, only anions of strong acids like sulfates are determined. The
      selectivity for sulfur-containing species is proved based on the specific
      isotopic ratios. In conjunction with the accurate mass from the time-of-flight
      mass spectrometer, the presented method is well suited for clinical and
      pharmaceutical applications to identify possible metabolites and to quantify
      known metabolites.

PMID- 22976088
TI  - Analysis of neurotransmitter amino acids by CE-LIF detection in biological
      fluids.
AB  - Neurotransmitter amino acids like Alanine (Ala), Glutamic acid (Glu), Aspartic
      acid (Asp), Serine (Ser), Taurine (Tau), and Glycine (Gly) are widely distributed
      in biological fluids and tissues and they have important physiological functions,
      so that the evaluation of their levels in organisms plays an essential role in
      physiology. We here report a new capillary electrophoresis (CE) method with laser
      induced fluorescence detection by which analytes are resolved and detected in
      less than 12 min both in human plasma and in other samples types, such as red
      blood cells, urine, cultured cells, cerebrospinal fluid, saliva, and vitreous
      humor, thus avoiding the typical limitations of the other methods normally
      suitable only in one or two matrix types.

PMID- 22976089
TI  - Expanded newborn screening of inborn errors of metabolism by capillary
      electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS).
AB  - Expanded newborn screening of inborn errors of metabolism (IEM) based on tandem
      mass spectrometry technology has emerged as one of the most successful
      preventative healthcare initiatives for presymptomatic diagnosis and treatment of
      rare yet treatable genetic diseases. However, confirmatory testing using methods
      with improved specificity is required in clinical laboratories to improve the
      positive predictive value for certain classes of IEMs due to their high rates of
      false positives. Here, we describe recent advances for comprehensive profiling of
      amino acids and acylcarnitines derived from dried blood spot extracts or plasma
      using capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI
      MS) that allows for resolution of major isobaric/isomeric interferences without
      complicated sample handling. The integration of online sample preconcentration
      together with desalting in CE-ESI-MS enables the direct analysis of hydrophilic
      amino acids, surface-active acylcarnitines, as well as labile thiols under a
      single format when using a simple aqueous buffer electrolyte system.

PMID- 22976090
TI  - Development of an on-site measurement system for salivary stress-related
      substances based on microchip CE.
AB  - Secretory immunoglobulin A (sIgA) in saliva has been suggested to be a potential
      marker of chronic, long-term stress due to suppression of the immune system. A
      rapid point-of-care testing platform for stress measurement based on immunoassay
      and capillary electrophoresis (CE) separation was -developed using a poly(methyl
      methacrylate) (PMMA) chip and a laboratory-built microchip CE system. A method
      for the quantitative determination of sIgA in human saliva is introduced.

PMID- 22976091
TI  - Simultaneous determination of atenolol and amiloride by capillary electrophoresis
      with capacitively coupled contactless conductivity detection (C4D).
AB  - Capillary electrophoresis coupled with a capacitively coupled contactless
      conductivity detector (CE-C(4)D) has been employed for the determination of the
      beta-blocker drugs (atenolol and amiloride) in pharmaceutical formulations. 150
      mM acetic acid was used as background electrolyte. The influence of several
      factors (detector excitation voltage and frequency, buffer concentration, applied
      voltage, capillary temperature, and injection time) was studied. Non-UV absorbing
      L-valine was used as an internal standard; the analytes were all separated in
      less than 7 min. The separation was carried out in normal polarity mode at 28 
      degrees C, 25 kV, and using hydrodynamic injection (25 s). The separation was
      effected in a bare fused-silica capillary 75 MUm * 52 cm. The CE-C(4)D method was
      validated with respect to linearity, limit of detection and quantification,
      accuracy, precision, and selectivity. Calibration curves were linear over the
      range 5-250 MUg mL(-1) for the studied analytes. The relative standard deviations
      of intra- and inter-day precisions of migration times and corrected peak areas
      were less than 6.0%. The method showed good precision and accuracy and was
      successfully applied to the simultaneous determination of the beta-blocker drugs
      in different pharmaceutical tablets.

PMID- 22976093
TI  - High-throughput profiling of the serum N-glycome on capillary electrophoresis
      microfluidics systems.
AB  - Glycosylation research has gained significant attention in several research
      fields including immunology, protein production, and biomarker discovery.
      However, complex and time-consuming protocols are often necessary to obtain
      suitable samples for analysis. We here describe a short and robust assay to
      prepare 8-aminopyrene-1,3,6-trisulphonic acid-labeled N-glycans from serum
      samples. It only involves the subsequent addition of reagents and incubation in a
      PCR thermocycler. Moreover, this assay allows the detection of these glycans,
      which are only present in minute amounts in serum, on high-throughput
      microfluidics CE platforms including the MCE-202 MultiNA, 2100 Bioanalyzer, and
      eGene system. Using this clinical glycomics assay, we could reliably measure
      GlycoHepatoTest, a panel of biomarkers allowing the follow-up of chronic liver
      disease patients from the early stage onward.

PMID- 22976092
TI  - A homogeneous immunoassay of thyroxine based on microchip electrophoresis and
      chemiluminescence detection.
AB  - A homogeneous chemiluminescent immunoassay of thyroxine (T4) present in serum
      samples is described. The proposed method deployed the competitive immunoreaction
      of T4 and horseradish peroxidase (HRP)-labeled T4 (HRP-T4) with anti-T4 mouse
      monoclonal antibody (Ab). HRP-T4 and the HRP-T4-Ab complex were separated and
      quantified by using microchip electrophoresis (MCE) with chemiluminescence (CL)
      detection. The MCE separation was accomplished within 60 s. Highly sensitive CL
      detection was achieved by means of HPR-catalyzed luminol-H(2)O(2) reaction. The
      linear range for T4 was 5-250 nM with a detection limit of 2.2 nM (S/N = 3).

PMID- 22976094
TI  - Screening of matrix metalloproteinase inhibitors by microanalysis with
      fluorescence detection.
AB  - Capillary electrophoresis has emerged as a small-scale analytical tool for enzyme
      assays. It is not only used to analyze and follow-up enzymatic reactions in an
      offline mode, but the reaction can also be performed online, inside the
      capillary, where the reaction products are formed and analyzed. In this way, an
      integrated setup is obtained which allows a higher degree of automation and
      miniaturization in analytical systems. This chapter presents an
      electrophoretically mediated microanalysis for in vitro characterization and
      screening of matrix metalloproteinase inhibitors.

PMID- 22976095
TI  - ABO genotyping by capillary electrophoresis.
AB  - Single-strand conformation polymorphism by capillary electrophoresis (SSCP-CE)
      has been developed to detect single nucleotide mutations. This method is used to
      identify the ABO alleles A(1), A(1v), B, O(1), O(1v), and O(2) in this chapter.
      Four amplicons (112, 121, 123, and 160 bp) labeled with fluorescence are
      separately amplified by polymerase chain reaction from exons 6 and 7 of ABO gene.
      These four fragments are combined into a single tube for SSCP-CE analysis using
      native gel to identify their single nucleotide polymorphism. This method can fast
      screen ABO genotypes from unknown samples and will be valuable in clinical
      transfusion or forensic applications.

PMID- 22976096
TI  - Separation of hemoglobin variants by capillary electrophoresis.
AB  - Quantitative defects in hemoglobin (Hb) are represented by Hb variants, where the
      amino acids sequence is modified as a consequence of a mutation in the alpha or
      beta-globin genes. More than 1,100 variants have been described so far but only a
      few dozen are clinically significant; the most significant being Hb S, which in
      the homozygous state causes sickle cell disease. The majority of the methods used
      to detect Hb variants are based on the charge difference of the mutated globin
      chain. We have developed a micellar capillary electrophoresis (MEKC) method using
      highly acidic conditions and a high Triton((r)) concentration. Separation times
      in the order of 20 min were able to resolve all normal and 29 abnormal globin
      chains including Hb E. This method was initially developed for Beckman P/ACE 5500
      Instrument but has been modified for the more recent P/ACE MDQ and PA 800
      instruments; however, the method can be adapted to any kind of CE analyzer.

PMID- 22976097
TI  - Newborn screening for hemoglobinopathies using capillary electrophoresis.
AB  - This chapter reports the essential elements needed to understand basic laboratory
      diagnostics consisting of separation and measurement of the hemoglobin fractions.
      Although well established, basic diagnostics require some background and some
      degree of experience for application and interpretation. Last generation methods,
      consisting of automatic systems like high performance liquid chromatography and
      capillary electrophoresis (CE), allow high through put analysis in adults and
      newborns. Newborn screening using CE is presented in some details, using as an
      example the Capillarysa Neonat Hb system (Sebia, France), as an upcoming
      alternative, explaining the method, the interpretation of the results, the
      objectives, the follow up, the advantages, and the pitfalls.

PMID- 22976098
TI  - Application of CZE in the differentiation of Staphylococcus aureus strains.
AB  - Precise, fast, and cheap identification of pathogenic bacteria is a key factor of
      microbial diagnostics. Application of analytical techniques can provide new
      possibilities in this regard. The bacterial pathogen Staphylococcus aureus is
      responsible for a number of serious human infections which are hard for
      eradication since the number of multidrug resistant isolates is increasing. In
      the present chapter, we describe novel methods based on capillary zone
      electrophoresis (CZE) and (as confirmation of these results) molecular analysis
      of a part of the coag gene for identification and differentiation of S. aureus
      strains.

PMID- 22976099
TI  - Multiplex and quantitative pathogen detection with high-resolution capillary
      electrophoresis-based single-strand conformation polymorphism.
AB  - Among the molecular diagnostic methods for bacteria-induced diseases, capillary
      electrophoresis-based single-strand conformation polymorphism (CE-SSCP) combined
      with 16S rRNA gene-specific PCR has enormous potential because it can separate
      sequence variants using a simple procedure. However, conventional CE-SSCP systems
      have limited resolution and cannot separate most 16S rRNA gene-specific markers
      into separate peaks. A high-resolution CE-SSCP system that uses a
      poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) triblock copolymer
      matrix was recently developed and shown to effectively separate highly similar
      PCR products. In this report, a protocol for the detection of 12 pathogenic
      bacteria is provided. Pathogen markers were amplified by PCR using universal
      primers and separated by CE-SSCP; each marker peak was well separated at baseline
      and showed a characteristic mobility, allowing the easy identification of the
      pathogens.

PMID- 22976100
TI  - Application of CGE to virus identification.
AB  - Protein profiling is an increasingly valuable tool for the characterization of
      protein populations and has been used to identify microorganisms, most often
      using two-dimensional gel electrophoresis followed by mass spectrometry. We
      present a rapid method for the identification of viruses using microfluidic chip
      gel electrophoresis (CGE) of high-copy number proteins to generate unique protein
      profiles. Viral proteins are solubilized, fluorescently labeled and then analyzed
      using the MUChemLabTM CGE system (~10 min overall). A Bayesian classification
      approach is used to classify the reproducible and visually distinct protein
      profiles of MS2 bacteriophage, Epstein-Barr, Respiratory Syncytial, and Vaccinia
      viruses as well as discriminate between closely related T2 and T4 bacteriophage.

PMID- 22976101
TI  - Capillary electrophoresis-based proteomic techniques for biomarker discovery.
AB  - Besides proteome complexity, the greatest bioanalytical challenge facing
      comprehensive proteomic analysis, particularly in the identification of low
      abundance proteins, is related to the large variation of protein relative
      abundances. In contrast to universally enriching all analytes by a similar
      degree, the result of the capillary isotachophoresis (CITP) stacking process is
      that major components may be diluted, but trace compounds are concentrated. Such
      selective enhancement toward low abundance proteins drastically reduces the range
      of relative protein abundances within complex proteomes and greatly enhances the
      resulting proteome coverage. Furthermore, CITP offers seamless combination with
      nano-reversed phase liquid chromatography (nano-RPLC) as two highly resolving and
      completely orthogonal separation techniques critically needed for analyzing
      complex proteomes.

PMID- 22976102
TI  - Integrated affinity and electrophoresis systems for multiplexed biomarker
      analysis.
AB  - The integration of affinity columns in microfluidic devices generates a micro
      total analysis system which has high value in applications such as analyte
      extraction and preconcentration. In this chapter we describe the preparation of
      affinity columns in situ by photopolymerization of acrylate monomers. The epoxy
      groups on the columns are further functionalized with antibodies to form affinity
      columns. We describe in detail the use of our affinity columns in extracting
      cancer biomarkers from model mixtures and blood serum. The purified biomarkers
      are then eluted from the column, separated by microchip capillary
      electrophoresis, and detected by laser-induced fluorescence. Our procedures allow
      efficient sample pretreatment and preconcentration, as well as simultaneous and
      rapid quantification of multiple biomarkers.

PMID- 22976103
TI  - Urinary proteomics based on capillary electrophoresis coupled to mass
      spectrometry in kidney disease.
AB  - Urine is an excellent sample source in the proteomic study of diseases. It is
      available in large quantities, is relatively stable, is not contaminated by cells
      or lipids, and has shown to provide information not only on the organs in contact
      with the urinary tract but also of more remote organs and tissues. In addition to
      these qualities, it can be collected by untrained personnel. For these reasons,
      urinary proteomic studies have escalated in recent years with the aim of
      identifying biomarkers that could be use for diagnosis or to predict the outcome
      of renal pathologies. In this chapter, we present one of the analytical platforms
      that has been successfully used in a number of studies for the identification and
      validation of biomarkers in kidney diseases. This technique is capillary
      electrophoresis coupled online to an electrospray ionization time-of-flight mass
      spectrometer (CE-MS). This technology has proven to be highly reproducible,
      sensitive with a quick analysis time, important features when analytical
      platforms have to be used in a clinical setting.

PMID- 22976104
TI  - Immunoaffinity, capillary electrophoresis, and statistics for studying intact
      alpha 1-acid glycoprotein isoforms as an atherothrombosis biomarker.
AB  - Variations in the amino acid sequence, glycosylation, and/or other
      posttranslational modifications in glycoproteins give rise to different molecules
      of the glycoprotein called forms. Qualitative and/or quantitative alterations in
      these forms are related to pathophysiological situations in the individuals. In
      this study, a methodology to analyze these differences in forms of the alpha 1
      acid glycoprotein (AGP) between healthy individuals and patients with two
      different vascular diseases is detailed. The whole methodology includes a sample
      preparation method based on immunochromatography, a capillary electrophoresis
      method for separation of AGP peaks (isoforms), and statistical methods (Linear
      Discriminant Analysis) for sample classification. As a result, it is shown that
      the methodology proposed allows studying the role of AGP isoforms as potential
      vascular disease biomarkers.

PMID- 22976105
TI  - Chip-based immunoassays.
AB  - Microfluidic immunoassay techniques offer advantages in speed, automation, and
      portability over -bench-top gold standard counterparts. In particular, on-chip
      immunosubtraction is a rapid homogeneous immunoassay used for reporting both
      protein native mobility and binding specificity. Immunosubtraction is performed
      by removing antibody-bound target proteins from electrophoretic detection via a
      size-based exclusion filter, while unbound nontarget proteins are able to pass
      through the filter for downstream detection. Immunosubtraction is achieved on
      chip by fabrication of discrete patterned polyacrylamide (PA) gel regions.
      Additionally, PA gel regions are used to define on-chip sample preparation
      regions for protein enrichment, fluorescent labeling, and antibody-target binding
      prior to immunosubtraction. Here we describe the immunosubtraction device
      fabrication technique as well as the electrophoretic assay protocol for
      determining target protein mobility and binding specificity within complex
      biological samples including cerebrospinal fluid.

PMID- 22976106
TI  - CE analysis of gamma-globulin mobility and potential clinical utility.
AB  - Serum protein electrophoresis is widely used in clinical laboratories to measure
      the relative abundance of each obtained fraction. Moreover, we found that the
      migration time of the gamma-globulin fraction can be reproducibly determined (CV
      = 1.1%). Immunoglobulins were purified from serum using protein L-agarose and
      their N-glycosylation was studied using CE on a DNA sequencer. Liver fibrosis
      patients showed a lower level of sialylation and this moderately correlates with
      the migration time of the gamma-globulins (r = 0.2-0.4). This allowed us to
      differentiate healthy individuals from these patients with an acceptable
      diagnostic accuracy (area under the curve = 0.75). This glycomics approach could
      become a significant added value to a daily, routine clinical test.

PMID- 22976107
TI  - Cytokine analysis by immunoaffinity capillary electrophoresis.
AB  - Immunoaffinity capillary electrophoresis (ICE) is a powerful tool used to detect
      and quantify target proteins of interest in complex biological fluids. The target
      analyte is captured and bound to antibodies immobilized onto the wall of a
      capillary, labeled in situ with a fluorescent dye, eluted and detected online
      using laser-induced fluorescence following electrophoretic separation. Here, we
      illustrate how to construct an immunoaffinity capillary and utilize it to run ICE
      in order to capture and quantify target cytokines and chemokines from a clinical
      sample.

PMID- 22976108
TI  - Capillary electrophoresis for the detection of Fragile X expanded alleles.
AB  - Capillary electrophoresis is an analytical technique that separates ions based on
      their electrophoresis mobility with the use of an applied voltage. Capillary
      electrophoresis is used most predominantly in nuclear acid fragment analysis as
      well as DNA sequencing because it gives faster results and provides high
      resolution separation. Here we describe an application using capillary
      electrophoreses for screening the Fragile X expanded alleles to demonstrate the
      application.

PMID- 22976109
TI  - Analysis of microsatellite instability by microfluidic-based electrophoresis.
AB  - Microsatellites are short repetitive sequences of two, three, or four bases,
      prone to base mispairing. Microsatellite instability (MSI) occurs frequently in
      various types of cancer due to a defective DNA mismatch repair system. Therefore,
      MSI analysis is an important tool in clinical research and molecular diagnostics.
      Mostly, polyacrylamide gel electrophoresis or capillary electrophoresis of
      labeled microsatellite sequences is used for the detection of MSI. Here we
      present a microfluidic-based electrophoresis technology for MSI analyses. Defined
      loci of microsatellites were PCR amplified and amplicons were analyzed by
      microfluidic-based electrophoresis. The electropherogram profiles of tumor and
      non-tumor derived DNA clearly revealed an individual pattern identifying
      differences in tumor-associated microsatellites. Detection of MSI by
      microfluidics turned out to be a simple and efficient procedure but less
      laborious than conventional approaches. Thus, the chip-based microfluidic
      electrophoresis is a simple, reliable, and robust technology for MSI detection,
      which allows label-free analyses of microsatellite amplicons within 30 min.

PMID- 22976110
TI  - HLA DR-DQ genotyping by capillary electrophoresis for risk assessment for celiac
      disease.
AB  - The risk for celiac disease (CD) is clearly related to specific HLA DQA1 and DQB1
      alleles, but HLA -typing is often considered too costly for frequent use.Here we
      present a method using sequence-specific primed PCR (PCR-SSP) for HLA-DR-DQ
      genotyping optimized for capillary electrophoresis on Applied Biosystems 3130xl
      Genetic Analyzer. Requiring a total of three PCR reactions and a single
      electrophoretic step, this method reduces the reagent expenses and technical time
      for directed HLA typing to distinguish risk alleles for CD, with a sufficient
      throughput for large-scale screening projects.

PMID- 22976111
TI  - Anxiety-related behavior of orphan chimpanzees (Pan troglodytes schweinfurthii)
      at Gombe National Park, Tanzania.
AB  - This study examined the anxiety levels and social interactions of two orphan and
      four mother-reared adolescent chimpanzees (Pan troglodytes schweinfurthii) in the
      Kasekela community at Gombe National Park, Tanzania. We used focal sampling in
      the field at Gombe to observe these adolescent individuals. Their social
      interactions and anxious behavior, measured as rough scratching, were recorded.
      The two orphans differed from others of a similar age by exhibiting higher levels
      of anxiety and lower levels of play. These results suggest that a mother's
      absence, even in naturalistic conditions in which other members of the community
      are available to the orphan, may have long-lasting impact on an adolescent's
      anxiety and its ability to engage in complex social interactions, such as play.

PMID- 22976112
TI  - Cannabinoid Receptor 1 (CNR1) 4895 C/T Genetic Polymorphism was Associated with
      Obesity in Japanese Men.
AB  - AIM: The aim of this study was to investigate the association of cannabinoid
      receptor 1 (CNR1) 4895 C/T gene polymorphism with obesity and obesity-related
      cardiovascular disease (CVD) risk factors in Japanese. METHOD: This study
      included 1,452 Japanese (678 men and 774 women, aged 25 to 74) from rural
      communities in Shimane Prefecture, Japan. RESULTS: The frequency of the C minor
      allele of CNR1 4895 C/T polymorphism was 47%. In men, the CC genotype carriers
      showed significantly greater body mass index (BMI) and waist circumference (WC)
      values than T allele carriers, even after adjusting for age and medications for
      hypertension, dyslipidemia and type 2 diabetes. The frequency of obesity (BMI
      >=25 kg/m(2)) in CC genotype carriers was significantly greater than in T allele
      carriers (31.8% vs 21.5%), but the frequency of central obesity (WC >=85 for men
      and WC >=90 cm for women) was not significant by CNR1 4895 C/T genotype. CC
      genotype carriers of CNR1 4895 C/T showed, in logistic regression analysis,
      significantly greater odds for obesity than T allele carriers, even after
      adjustment for age and the above-mentioned medications. Systolic blood pressure
      (SBP) values were also significantly different between the CC genotype and T
      allele carriers after controlling for age, medications for hypertension,
      dyslipidemia, and type 2 diabetes, and BMI or WC. CONCLUSION: This study supports
      the association of CNR1 4895 C/T with interindividual differences in obesity in
      men.

PMID- 22976113
TI  - A "ship-in-a-bottle" approach to synthesis of polymer dots@silica or polymer
      dots@carbon core-shell nanospheres.
AB  - A "ship-in-a-bottle" approach to the entrapment and assembly of nanometer-sized
      polymer dots in hollow silica or carbon nanospheres with size-selective
      micropores is presented. This new type of core-shell nanospheres exhibits
      excellent photoluminescence properties and significant adsorption capabilities
      for transition-metal ions.

PMID- 22976114
TI  - Unrelated cord blood transplantation for patients with adult T-cell
      leukemia/lymphoma: experience at a single institute.
AB  - We report the results of unrelated cord blood transplantation (UCBT) for patients
      with adult T-cell leukemia/lymphoma (ATLL) conducted in our single institute. Ten
      patients with ATLL (nine acute and one lymphoma-type) received UCBT during the
      period from August 2003 to July 2011. The median age at the time of diagnosis of
      ATLL was 51 years (range 37-64). The median period from diagnosis of ATLL to UCBT
      was 130 days (range 94-344). Conditioning regimens were myeloablative for six and
      reduced intensity for four. The median number of infused nucleated cells and CD34
      positive cells were 2.52 * 10(7)/kg and 1.04 * 10(5)/kg, respectively. There was
      no engraftment failure. Three patients developed grade II acute graft versus host
      disease, and four developed grade III. The estimated 2-year overall survival was
      40 % (95 % CI 12-67 %). Four of six chemosensitive patients prior to UCBT
      survived for 1035, 793, 712, and 531 days post-UCBT, respectively. There were no
      survivors among the four chemorefractory patients prior to UCBT. Our data
      indicates that UCBT is feasible and provides long-term survival in patients with
      chemosensitive ATLL.

PMID- 22976116
TI  - Air quality biomonitoring through pollen viability of Fabaceae.
AB  - In this study, pollen viability and germination of three plant species, Cercis
      siliquastrum L., Robinia pseudoacacia L., and Spartium junceum L., belonging to
      the Fabaceae family, was evaluated in sites with different intensity of road
      traffic, constantly monitored with continuous analysers for air pollutants
      (carbon monoxide (CO), sulphur dioxide (SO(2)), and nitrogen dioxide (NO(2))) by
      the Municipality of Catania. Two sites, in which road traffic was absent, were
      selected, too. The percentages of viable pollen by 2,3,5-trypheniltetrazolium
      chloride (TTC) test ranged from 59.0 to 90.2 % in C. siliquastrum, from 61.5 to
      83.5 % in S. junceum and from 67.5 to 84.3 % in R. pseudoacacia. The percentages
      of germination varied from 41.0 to 72.7 % in C. siliquastrum, from 42.0 to 64.7 %
      in S. junceum and from 38.3 to 66.3 % in R. pseudoacacia. The highest percentages
      of viable pollens were found in no-road traffic stations by either TTC or
      germination tests, while the lowest values were detected in a site characterised
      by heavy road traffic. In the monitored period (2007-2009), pollen viability,
      germinability and tube length of C. siliquastrum resulted in a significant
      negative correlation to CO, SO(2) and NO(2), whereas data from TTC and
      germination tests on S. junceum and R. pseudoacacia pollens were not well
      correlated to air pollutants. The results showed that pollen viability,
      germination and tube growth in C. siliquastrum were affected by air pollution. S.
      junceum and R. pseudoacacia were not very influenced by air pollutants,
      suggesting a different pollen sensitivity of these species.

PMID- 22976117
TI  - A native species-based index of biological integrity for Hawaiian stream
      environments.
AB  - Based upon ecological data provided by a 6-year study of native species
      assemblage structure and function in near-pristine Limahuli Stream (Kauai), The
      Hawaii Stream Index of Biological Integrity (HS-IBI) incorporates 11 metrics
      covering five ecological categories (taxonomic richness, sensitive species,
      reproductive capacity, trophic-habitat capacity, and tolerance capacity). The HS
      IBI was shown to effectively distinguish stream biological condition on a
      continuum from undisturbed (near-pristine) to severely impaired in sampling of 39
      sites (6 estuarine reaches) on 18 Hawaiian streams located on all major islands.
      A significant relationship was validated between relative levels of human impact
      occurring within-watersheds (determined through use of a landscape indicator) and
      IBI ratings with metrics responding predictably to gradients of human influence.
      For management interpretation of HS-IBI results, a framework comprised of five
      "integrity classes" (excellent-good-fair-poor-impaired) is provided which can be
      used to operationalize HS-IBI results obtained through standardized sampling of
      stream sites that "...translates into a verbal and visual portrait of biological
      condition." Through its focus on native species, the HS-IBI incorporates
      evolutionary and biogeographic variation for the region with biological
      expectations based upon reference condition benchmarks established in near
      pristine stream environments where ecological functioning is naturally self
      sustaining and resilient to normal environmental variation. The methods and tools
      described in this study are appropriate for application in all perennial streams
      in Hawaii and may be adapted for use in streams on other tropical Pacific islands
      where native species assemblages persist in near-pristine stream environments.

PMID- 22976118
TI  - Specific absorption and backscattering coefficients of the main water
      constituents in Poyang Lake, China.
AB  - Obtaining and analyzing the specific inherent optical properties (SIOPs) of water
      bodies is necessary for bio-optical model development and remote sensing-based
      water quality retrievals and, further, for related ecological studies of aquatic
      ecosystems. This study aimed to measure and analyze the specific absorption and
      backscattering coefficients of the main water constituents in Poyang Lake, China.
      The specific absorption and/or backscattering coefficients of the main water
      constituents at 85 sampling sites (47 in 2010 and 38 in 2011) were measured and
      analyzed as follows: (1) the concentrations of chlorophyll a (C(CHL)), suspended
      particulate matter (C(SPM)) (including suspended particulate inorganic matter
      (C(SPIM)) and suspended particulate organic matter (C(SPOM))), and the absorption
      coefficients of total particulate (a(p)), phytoplankton (a(ph)), and non-pigment
      particulate (a(d)) were measured in the laboratory; (2) the total backscattering
      coefficients at six wavelengths of 420, 442, 470, 510, 590, and 700 nm, including
      the contribution of pure water, were measured in the field with a HydroScat-6
      backscattering sensor, and the backscattering coefficients without the
      contribution of pure water (b(b)) were then derived by subtracting the
      backscattering coefficients of pure water from the total backscattering
      coefficients; (3) the specific absorption coefficients of total particulate
      (a*(p)), phytoplankton (a(ph)*), and non-pigment particulate (a*(d)) were
      calculated by dividing a(p), a(ph), and ad by C(SPM), C(CHL), and C(SPIM),
      respectively, while the specific backscattering coefficients of total suspended
      particulate matter (b*(b)) were calculated by dividing b(b) by CSPM; and (4) the
      a(ph)*, a*(d), a*(p) and b*(b) of the remaining samples (46 in 2010 and 36 in
      2011) were visualized and analyzed, and their relations to CCHL, CSPIM or CSPM
      were studied, respectively. The main results are summarized as follows: (1) the
      a(ph)* values at 440 nm were 0.0367-0.7203 m(2) mg(-1) with a mean of 0.1623 +/-
      0.1426 m(2) mg(-1) in 2010 and 0.0319-0.7735 m(2) mg(-1) with a mean of 0.3145 +/
      0.1961 m(2) mg(-1) in 2011; there existed significant, negative, and moderate
      correlations between a(ph)* and C(CHL) at 400-700 nm in 2010 and 2011 (p<0.05);
      (2) The a*(d) values at 440 nm were 0.0672-0.2043 m(2) g(-1) with a mean of
      0.1022 +/- 0.0326 m(2) g-1) in 2010 and 0.0559-0.1347 m(2) g(-1) with a mean of
      0.0953 +/- 0.0196 m(2) g(-1) in 2011; there existed negative correlations between
      a*(d) and C(SPIM), while the correlations showed overall decreasing and
      increasing trends before and after around 575 nm with increasing wavelengths,
      respectively; (3) The a*(p) values at 440 nm were 0.0690-0.1929 m(2) g(-1) with a
      mean of 0.1036 +/- 0.0298 m(2) g(-1) in 2010 and 0.0571-0.1321 m(2) g(-1) with a
      mean of 0.1014 +/- 0.0191 m(2) g(-1) in 2011, and the negative correlations
      between a*(p) and C(SPM) were found in both years; (4) The b*(b) at the six
      wavelengths generally decreased with increasing wavelengths, while the b*(b)
      values at 420 nm were lower than those at 442 nm for some samples; the
      correlation between b*(b) and C(SPM) increased with increasing wavelength. Such
      results can only represent the SIOPs during the sampling time periods, and more
      measurements and analyses considering different seasons need to be carried out in
      the future to comprehensively understand the SIOPs of Poyang Lake.

PMID- 22976119
TI  - Effects of a constructed wetland and pond system upon shallow groundwater
      quality.
AB  - Constructed wetland (CW) and constructed pond (CP) are commonly utilized for
      removal of excess nutrients and certain pollutants from stormwater. This study
      characterized shallow groundwater quality for pre- and post-CW and CP system
      conditions using data from monitoring wells. Results showed that the average
      concentrations of groundwater phosphorus (P) decreased from pre-CW to post-CW but
      increased from pre-CP to post-CP. The average concentrations of groundwater total
      Kjeldahl nitrogen and ammonium (NH(4)(+)) increased from pre-CW (or CP) to post
      CW (or CP), whereas the average concentrations of groundwater arsenic (As),
      chromium, nickel, and zinc (Zn) decreased from pre-CW to post-CW regardless of
      the well locations. Variations of groundwater cadmium, copper, and Zn
      concentrations were larger in pre-CP than in post-CP and had a tendency to
      decrease from pre-CP to post-CP. In general, the average concentrations of
      groundwater aluminum and manganese decreased and of groundwater calcium, iron,
      magnesium, and sodium increased from pre-CP to post-CP. The average values of
      water levels (depth from the ground surface), redox potential, and conductance
      decreased and of chloride and sulfate (SO(4)(-2)) increased after the wetland and
      pond were constructed regardless of the well locations. Results further revealed
      that there were significant differences (alpha = 0.05) between the pre- and post
      CW (or CP) for redox potential, water level, and As. This study suggests that the
      CW-CP system had discernible effects on some of the shallow groundwater quality
      constituents. This information is very useful for fully estimating overall
      performance of stormwater treatment with the CW-CP system.

PMID- 22976120
TI  - A spatial analysis of pit latrine density and groundwater source contamination.
AB  - This study aims to assess the relationship between chemical and microbial
      contamination of groundwater sources and a range of potential hazards in two peri
      urban areas of Kisumu, Kenya where shallow wells and pit latrines are widely
      used. From 1998 to 2004, 263 samples were taken from 61 groundwater sources and
      tested for thermotolerant coliforms. Eighteen of these sources were also tested
      for chemical contaminants, including nitrate, chloride and fluoride. The
      locations of all water sources, buildings and pit latrines in the study area were
      surveyed. Local pit latrine densities were calculated using a geographic
      information system. Ten out 18 samples were above the World Health Organization
      guideline values for nitrate, 236 out of 263 were positive for thermotolerant
      coliforms, and all were above the guideline values for fluoride. There was
      neither a relationship between thermotolerant coliform levels and daily rainfall
      patterns nor with sanitary risk inspection scores for samples from shallow wells
      (r = 0.01, p = 0.91, n = 191). The density of pit latrines within a 100-m radius
      was significantly correlated with nitrate and chloride levels (r = 0.64, p =
      0.004 and r = 0.46, p = 0.05, respectively) but not with thermotolerant coliforms
      (r = 0.22, p = 0.11). These results illustrate both the public health risks
      associated with shallow groundwater sources, on-site sanitation and high
      population density. These findings have implications for current policies that
      promote latrine construction, especially in peri-urban areas of high population
      density. More comprehensive studies of larger communities should be commissioned
      to extend this analysis of the links between latrine density and groundwater
      contamination and so identify the contingent policy risks.

PMID- 22976121
TI  - Three years monitoring survey of pesticide residues in Sardinia wines following
      integrated pest management strategies.
AB  - This paper reports the results of a pesticide monitoring survey on wine grapes
      from the 2008-2010 vintage from vineyards grown according to integrated pest
      management strategies. A multi-residue gas chromatography-mass spectrometry
      method in electron ionization and chemical ionization mode has been used for the
      determination of 30 pesticides in wine samples. The analytical method showed good
      recoveries and allowed a good separation of the selected pesticides.
      Repeatability and intermediate precision showed good results with CV < 20 %. The
      instrumental method limits of determination (LOD) and of quantification (LOQ)
      were below the maximum residue levels set in wine. The analysis of the wines
      showed that pesticide residues were below the instrumental LOQ, and most of them
      were undetectable (<LOD). Only the 38 % of the pesticide applied has been
      detected in at least one cultivar. Metalaxil, myclobutanil, and penconazole were
      the pesticides most frequently found, while carignano and vermentino were the
      cultivars with the higher number of residues.

PMID- 22976122
TI  - Low levels of plasma IGF-1 inhibit intracortical bone remodeling during aging.
AB  - Studies linking insulin-like growth factor-1 (IGF-1) to age-related bone loss in
      humans have been reported but remain only correlative. In this investigation, we
      characterized the bone phenotype of aged WT C57BL/6J male mice in comparison to
      that of C57BL/6J mice with reduced serum IGF-1 levels arising from an igfals gene
      deletion (ALS knockout (ALSKO)). During the aging process, WT mice showed an
      increase in fat mass and decrease lean mass while ALSKO mice had stable lean and
      fat mass values. Skeletal analyses of femora from WT mice revealed an expansion
      of the marrow area and a significant accumulation of intracortical porosity
      associated with increased intracortical remodeling. In contrast, ALSKO mice
      showed only small age-related declines in the amount of cortical bone tissue and
      minimal intracortical porosity, at 2 years of age. Accordingly, mechanical tests
      of femora from 2-year-old WT mice revealed reduced stiffness and maximal load
      when compared to bones from ALSKO mice. We show here that lifelong reductions in
      serum IGF-1 compromise skeletal size in development leading to slender bones;
      they are also associated with decreased intracortical bone remodeling and
      preservation of bone strength during aging. 

PMID- 22976124
TI  - Potential increase in mating frequency of queens in feral colonies of Bombus
      terrestris introduced into Japan.
AB  - With the exception of several species, bumblebees are monandrous. We examined
      mating frequency in feral colonies of the introduced bumblebee Bombus terrestris
      in Japan. Using microsatellite markers, genotyping of sperm DNA stored in the
      spermatheca of nine queens detected multiple insemination paternities in one
      queen; the others were singly mated. The average effective paternity frequency
      estimated from the genotypes of queens and workers was 1.23; that estimated from
      the workers' genotype alone was 2.12. These values were greater than those of
      laboratory-reared colonies in the native ranges of B. terrestris. The genotypes
      of one or two workers did not match those of their queens or showed paternities
      different from those of their nestmates; this may have arisen from either queen
      takeover or drifting of workers. These alien workers were responsible for the
      heterogeneous genotype distribution within each B. terrestris colony, resulting
      in higher estimates of paternity frequency than of insemination frequency. The
      high mating frequency of introduced B. terrestris may have occurred by artificial
      selection through mass breeding for commercialization. Moreover, polyandrous
      queens may be selectively advantageous, because reproduction by such queens is
      less likely to be disturbed by interspecific mating than that by monandrous
      queens.

PMID- 22976123
TI  - Chronic caffeine intake reverses age-induced insulin resistance in the rat:
      effect on skeletal muscle Glut4 transporters and AMPK activity.
AB  - The role of caffeine consumption on insulin action is still under debate. The
      hypothesis that chronic caffeine intake reverses aging-induced insulin resistance
      in the rat was tested in this work. The mechanism by which caffeine restores
      insulin sensitivity was also investigated. Six groups of rats were used: 3 months
      old (3 M), 3 months old caffeine-treated (3MCaf), 12 months old (12 M), 12 months
      old caffeine-treated (12MCaf), 24 months old (24 M), and 24 months old caffeine
      treated (24MCaf). Caffeine was administered in drinking water (1 g/l) during 15
      days. Insulin sensitivity was assessed by means of the insulin tolerance test.
      Blood pressure, body weight, visceral and total fat, fasting glycemia and
      insulinemia, plasma nonesterified fatty acids (NEFA), total antioxidant capacity
      (TAC), cortisol, nitric oxide, and catecholamines were monitored. Skeletal muscle
      Glut4 and 5'-AMP activated protein kinase (AMPK) protein expression and activity
      were also assessed. Aged rats exhibited diminished insulin sensitivity
      accompanied by hyperinsulinemia and normoglycemia, increased visceral and total
      fat, decreased TAC and plasma catecholamines, and also decreased skeletal muscle
      Glut4 and AMPK protein expression. Chronic caffeine intake restored insulin
      sensitivity and regularized circulating insulin and NEFA in both aging models.
      Caffeine neither modified skeletal muscle AMPK expression nor activity in aged
      rats; however, it decreased visceral and total fat in 12 M rats and it restored
      skeletal muscle Glut4 expression to control values in 24 M rats. We concluded
      that chronic caffeine intake reverses aging-induced insulin resistance in rats by
      decreasing NEFA production and also by increasing Glut4 expression in skeletal
      muscle.

PMID- 22976125
TI  - Association of the 54-nucleotide repeat polymorphism of hPer3 with opioid
      dependence in residents of the West Siberian region.

PMID- 22976126
TI  - Health care professionals as second victims after adverse events: a systematic
      review.
AB  - Adverse events within health care settings can lead to two victims. The first
      victim is the patient and family and the second victim is the involved health
      care professional. The latter is the focus of this review. The objectives are to
      determine definitions of this concept, research the prevalence and the impact of
      the adverse event on the second victim, and the used coping strategies. Therefore
      a literature research was performed by using a three-step search procedure. A
      total of 32 research articles and 9 nonresearch articles were identified. The
      second victim phenomenon was first described by Wu in 2000. In 2009, Scott et al.
      introduced a detailed definition of second victims. The prevalence of second
      victims after an adverse event varied from 10.4% up to 43.3%. Common reactions
      can be emotional, cognitive, and behavioral. The coping strategies used by second
      victims have an impact on their patients, colleagues, and themselves. After the
      adverse event, defensive as well as constructive changes have been reported in
      practice. The second victim phenomenon has a significant impact on clinicians,
      colleagues, and subsequent patients. Because of this broad impact it is important
      to offer support for second victims. When an adverse event occurs, it is critical
      that support networks are in place to protect both the patient and involved
      health care providers.

PMID- 22976127
TI  - Loss of CD44 attenuates aberrant GM-CSF signaling in Kras G12D hematopoietic
      progenitor/precursor cells and prolongs the survival of diseased animals.

PMID- 22976128
TI  - Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic
      myeloid leukemia cells.

PMID- 22976129
TI  - Solution properties of the Ln(III) complexes of a novel octadentate chelator with
      rigidified iminodiacetate arms.
AB  - A novel octadentate ligand derived from the core structure of EGTA
      (ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid) with two
      piperidine-cis-dicarboxylic acid moieties spaced by a triethylenedioxy chain (L1)
      has been synthesised with the aim to assess the effect of the structural rigidity
      on the thermodynamic and kinetic stabilities of its Ln(III) complexes. The
      stability constants of [Ln(L1)](-) complexes show a weaker binding affinity for
      Ln(3+) ions of L1 than EGTA. On the other hand, the selectivity of L1 for Ca(2+)
      over Mg(2+) is one of the highest ever reported. The kinetic inertness has been
      also investigated and faster rates of both acid catalysed and metal assisted
      decomplexation have been measured for [Gd(L1)](-) as compared to [Gd(EGTA)](-).
      The (1)H- and (13)C NMR spectra of the diamagnetic La(3+), Y(3+) and Lu(3+)
      complexes in aqueous media show pronounced stereochemical rigidity and the
      occurrence of a structural change across the lanthanide series. Finally, a
      complete (1)H and (17)O NMR relaxometric study indicates that [Gd(L1)](-)
      possesses a nine-coordinate ground state with one inner coordination sphere water
      molecule characterized by a fast rate of exchange ((298)k(ex) = 59 * 10(6) s(
      1)).

PMID- 22976131
TI  - Evaluation of hormonal suppression with two contraceptive regimens using ethinyl
      estradiol and desogestrel.
AB  - PURPOSE: Because of the lack of data on hormone levels in the hormone-free
      interval of the contraceptive regimens with desogestrel and ethynil estradiol,
      the objective of this study was to compare hormonal levels of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin B
      using two contraceptive regimens with those steroids. METHODS: Prospective and
      randomized study with 21 patients. Eleven patients received a 21/7 regimen (group
      1) and ten patients received a 21/2 placebo/5 ethinyl estradiol 10 MUg regimen
      (group 2). RESULTS: We found a significant increase in FSH and LH levels in both
      groups. There was a significant reduction of inhibin B in the 21/2/5 regimen. No
      difference in estradiol levels was found. CONCLUSIONS: Steroids withdrawal in the
      hormone-free interval causes reduced inhibition of the HPO axis. The significant
      decrease in inhibin B levels of group 2 suggests better suppression of the HPO
      axis in the 21/2/5 regimen.

PMID- 22976132
TI  - Obstetric and neonatal outcomes in a home-like birth centre: a case-control
      study.
AB  - PURPOSE: To compare the intervention rates associated with labor in low-risk
      women who began their labor in the "home-like birth centre" (HLBC) and the
      traditional labor ward (TLW). METHODS: This retrospective study used data that
      were collected from January 2005 to June 2008, from women admitted to the HLBC (n
      = 316) and compared to a group of randomly selected low-risk women admitted to
      the TLW (n = 890) using the Baysian information criterion to select the best
      predictive model. RESULTS: Women in the HLBC had spontaneous vaginal deliveries
      more often (88.6 vs. 82.8 %, p value 0.034) and perineal lesions less often (60.1
      vs. 62.5 %, p value 0.013). The frequency of adverse neonatal outcomes did not
      differ statistically between the two groups, although the mean clamped at birth
      umbilical arterial pH level was higher in the HLBC group. The transfer rate from
      HLBC to TLW was 31.3 % of which 75.8 % were nulliparae. CONCLUSIONS: It appears
      that women could benefit from HLBC care in settings such as the one studied.
      Larger observational studies are warranted to validate these results.

PMID- 22976134
TI  - Convection-enhanced delivery: from mechanisms to clinical drug delivery for
      diseases of the central nervous system.
AB  - The evolution of cancer chemotherapy has been a major advance in medical science
      in the late 20th century. However, patients with malignant gliomas have not
      benefitted much. The blood-brain barrier (BBB), which always hinders the entry of
      therapeutic agents into the central nervous system (CNS), may at least partly be
      responsible. Convection-enhanced delivery (CED), a method for distributing large
      and small molecular weight compounds bypassing the BBB, enables robust
      distribution of the infused molecules at the site of infusion. CED is promising
      as an effective treatment not only for malignant gliomas but also for multiple
      CNS disorders because this method can effectively distribute multiple molecules
      that are potentially effective against different diseases. Although the method is
      quite simple, several problems require solution in developing novel CED-based
      strategies, including what, where, when, and how to infuse. This review discusses
      basic considerations when developing CED-based strategies for CNS diseases,
      focusing mainly on brain tumors.

PMID- 22976133
TI  - A review and evaluation of the efficacy and safety of Cissus quadrangularis
      extracts.
AB  - Extracts and powders of Cissus quadrangularis have been used for many years to
      promote bone and tissues healing, as an analgesic, to treat infections, as an
      anabolic, and to promote weight loss and weight management. This review
      summarizes the studies in animals, humans and in vitro systems that have been
      conducted to determine the efficacy and safety of various Cissus preparations.
      Animal and in vitro studies provide support for the use of Cissus in promoting
      bone fracture healing and as an anti-osteoporotic. Several human studies support
      the use of Cissus extracts in weight management. No studies have been conducted
      demonstrating that Cissus exhibits anabolic and body building activities. Based
      on studies to date, Cissus extracts appear to be exceedingly safe and free of
      adverse effects at the doses commonly used. A wide variety of chemical
      constituents have been isolated and identified from Cissus extracts, including
      steroids, flavonoids, stilbenes, iridoids, triterpenes and gallic acid
      derivatives. However, in few cases have specific physiological effects been
      related to identifiable constituents. Better standardization of extracts and more
      well-controlled human studies are required.

PMID- 22976135
TI  - Cilengitide treatment for malignant glioma: current status and future direction.
AB  - Malignant glioma is the most common primary brain tumor and accounts for the
      majority of diagnoses. Treatment has involved a combination of surgery,
      radiation, and chemotherapy, yet these modalities rarely extend the life of the
      patient to more than one year from diagnosis. Integrins are expressed in tumor
      cells and tumor endothelial cells, and are important in angiogenesis and invasion
      in glioma. alphavbeta3 and alphavbeta5 integrins regulate cell adhesion, and
      inhibitors of these integrins suppress tumor growth in certain pre-clinical
      models. Several integrin-targeted drugs are in clinical trials as potential
      compounds for the treatment of cancer. Among them, cilengitide is a novel
      integrin antagonist for the treatment of glioblastoma. The multimodal anti-glioma
      effects are based on its cytotoxic, anti-angiogenic, anti-invasive, and
      synergetic effects. Preclinical studies showed a promising synergy between
      cilengitide and radiochemotherapy in order to normalize tumor vasculature and
      attenuate tumor invasion. Cilengitide is currently being assessed in phase III
      trials for patients with glioblastoma multiforme and in phase II trials for other
      types of cancers, demonstrating promising therapeutic outcomes to date. The
      results of these and other clinical studies are expected with great hope and
      interest. A more clear understanding of the benefits and pitfalls of each
      approach can then lead to the design of strategies to derive maximal benefit from
      these therapies.

PMID- 22976136
TI  - Efficacy and limitations of stereotactic radiosurgery in the treatment of
      glioblastoma.
AB  - Treatment of recurrent glioblastoma is still challenging. Stereotactic
      radiosurgery has been accepted as a treatment option for recurrent glioblastoma
      after standard chemotherapy and irradiation. However, the efficacy of
      stereotactic radiosurgery at recurrence has been limited, mainly due to the
      highly infiltrative nature of the tumor which makes the lesion difficult to
      define as the target. To enhance the efficacy of stereotactic radiosurgery,
      several methods of targeting based on neuroimaging technology such as positron
      emission tomography and magnetic resonance imaging have been adopted to irradiate
      as many of the viable tumor cells as possible and showed some enhanced efficacy.
      In a trial of intensified treatment by extending the irradiation field,
      improvement of local control did not result in longer survival. Radiation-induced
      adverse event is another problem after stereotactic radiosurgery for recurrent
      glioblastoma because almost all patients underwent irradiation as a part of the
      initial treatment. To overcome the side effects associated with re-irradiation,
      use of bevacizumab, a humanized monoclonal antibody to vascular endothelial
      growth factor, has shown some efficacy. Advances in irradiation technology,
      neuroimaging, and adjuvant treatment are needed to enhance the efficacy of
      stereotactic radiosurgery for recurrent glioblastoma and reduce the morbidity
      associated with irradiation.

PMID- 22976137
TI  - Usefulness of multimodal examination and intraoperative magnetic resonance
      imaging system in glioma surgery.
AB  - Extensive surgical removal of tumor tissue can contribute to longer survival for
      patients with gliomas. Intraoperative magnetic resonance (iMR) imaging is
      important for safe and maximal resection of brain tumors. A new operating room
      equipped with a 1.5-T MR imaging system and neuronavigation opened at Yamagata
      University Hospital in 2008. Using this new suite, we have safely treated over
      200 cases. Use of iMR imaging improved glioma resection rates in 25 (34%) of 73
      cases, and gross total resection was achieved in 48 patients (66%). Motor evoked
      potential (MEP) monitoring was performed in combination with iMR imaging for 32
      gliomas. MEP monitoring was successful in 30 cases (94%). Transient decreases in
      MEP amplitude were seen in two patients. One patient showed transient motor
      weakness and another showed improvement of motor function. The iMR imaging system
      provides useful information for tumor resection that allows intraoperative
      modification of surgical strategies. Combining MEP monitoring with iMR imaging
      appears to offer the most effective method for safe glioma surgery near eloquent
      areas.

PMID- 22976139
TI  - Ki-67 expression for predicting progression of postoperative residual pituitary
      adenomas: correlations with clinical variables.
AB  - Reliable prognostic parameters indicating progression in residual pituitary
      adenoma after surgery are necessary. The World Health Organization classification
      of tumors of endocrine organs defines atypical pituitary adenomas as tumor with
      Ki-67 labeling index higher than 3%, excessive p53 immunoreactivity, and
      increased pleomorphism. The real value of Ki-67 labeling index correlating with
      tumor progression is controversial. We investigated the relationship between
      positive labeling for MIB-1 and clinical features of 39 patients with pituitary
      adenomas with and without rapid re-growth after initial surgery. Ki-67 expression
      revealed pituitary adenomas with progression (re-growth within 5 years after
      initial surgery) had a mean proliferation index of 3.66 +/- 3.00% (mean +/-
      standard deviation [SD], n = 12), which was significantly higher than in tumors
      without progression of 1.89 +/- 1.25% (mean +/- SD, n = 27) (p < 0.05, Mann
      Whitney test). Receiver operating characteristic analysis showed a threshold
      level of Ki-67 expression greater than 2.0% predicts progression with high
      specificity. Younger patients had higher MIB-1 index and more progression (p <
      0.05). Adenomas with cavernous sinus invasion, functioning adenomas, and giant
      adenomas had higher MIB-1 index (p < 0.05). There was no significant correlation
      between tumor size or cavernous sinus invasion and progression. More completely
      removed tumors were less progressive. A threshold of 2% for the MIB-1 labeling
      index predicts higher risk of progression of residual adenomas after surgery, so
      shorter interval of follow-up neuroimaging, and early initiation of adjuvant
      therapy might be required.

PMID- 22976138
TI  - Rapid growth hormone measurement during transsphenoidal surgery: analysis of 252
      acromegalic patients.
AB  - The usefulness of rapid growth hormone (GH) measurement was retrospectively
      evaluated as an indicator of total tumor removal during surgery and compared with
      several reported criteria in 252 acromegalic patients who underwent
      transsphenoidal surgery at Toranomon Hospital between 2006 and 2008. GH levels
      were measured in blood samples obtained before surgery, at the start of tumor
      removal, and every 20 minutes thereafter until 20 minutes after total tumor
      removal as judged by the operator. Intraoperative GH dynamics were compared
      between 201 patients fulfilling the Cortina consensus criteria (successful group)
      and 37 patients who did not (unsuccessful group). Among several criteria
      indicating total tumor removal, only the ratio of serum GH level 20 minutes after
      the end of tumor removal to GH level at the end of tumor excision was
      significantly different between the groups; a reduction ratio of 65% was the most
      appropriate cut-off value based on sensitivity (59.2%) and specificity (59.5%).
      The ratio of GH level 20 minutes after the end of tumor removal/GH level at the
      end of tumor excision was the most reliable index to judge tumor removal during
      surgery, but this index is neither necessary nor sufficient and should be used as
      one of the indicators to judge complete tumor removal during surgery.

PMID- 22976140
TI  - Effectiveness of maximal safe resection for glioblastoma including elderly and
      low Karnofsky performance status patients: retrospective review at a single
      institute.
AB  - Elderly and low Karnofsky performance status (KPS) patients have been excluded
      from most prospective trials. This retrospective study investigated glioblastoma
      treatment outcomes, including those of elderly and low KPS patients, and analyzed
      the prognostic factors using the medical records of 107 consecutive patients, 59
      men and 48 women aged from 21 to 85 years (median 65 years), with newly diagnosed
      glioblastoma treated at our institute. There were 71 high-risk patients with age
      >70 years and/or KPS <70%. Based on the extent of resection, the patients were
      classified into 3 groups: more than subtotal resection (subtotal, n = 44),
      partial resection (partial, n = 29), and biopsy only (biopsy, n = 34). Median
      overall survival (OS) of all 107 patients was 13.5 months. Median OS was 13.2
      months in the high-risk group. Median OSs were 15.8, 12.8, and 12.1 months in the
      subtotal, partial, and biopsy groups, respectively. Multivariate analysis of 73
      patients in the subtotal and partial groups found age <=65 years (p = 0.047), 60
      Gy irradiation (p = 0.009), O(6)-methylguanine-deoxyribonucleic acid
      methyltransferase-negative (p = 0.027), and more than subtotal removal (p =
      0.003) were significant prognostic factors. The median postoperative KPS score
      tended to be better than the preoperative score, even in the high-risk group. We
      recommend maximal safe resection for glioblastoma patients, even those with
      advanced age and/or with low KPS scores.

PMID- 22976141
TI  - Patterns of intracranial glioblastoma recurrence after aggressive surgical
      resection and adjuvant management: retrospective analysis of 43 cases.
AB  - The present retrospective study evaluated the recurrence patterns after
      aggressive surgical removal of intracranial glioblastomas in 43 consecutive adult
      patients. The resection rate of the enhanced lesion on magnetic resonance imaging
      was 100% and 95-99% in 22 and 21 cases, respectively. All patients received
      postoperative fractionated radiotherapy (60 Gy in 30 fractions) with additional
      chemotherapy (25 cases) or vaccine therapy (18 cases). During follow-up (median
      17 months), tumor recurrence was identified in 33 patients, most frequently
      regional within the wall of the resection cavity (20 cases). No clinical factor
      differed significantly between the groups of patients with regional or marginal
      tumor progression (N = 22) and patients with distant or multiple recurrences (N =
      8). Progression-free survival did not differ significantly between these two
      groups (p = 0.27). However, overall survival was significantly longer (p = 0.04)
      in patients with regional or marginal tumor progression, and constituted 90% and
      54% at 1 and 2 years after surgery, respectively, compared to 75% and 0% in
      patients with distant or multiple recurrences. Aggressive surgical resection and
      adjuvant management of intracranial glioblastoma may change its recurrence
      pattern. Tumor progression appears in the wall of the resection cavity or within
      2 cm from its margin in approximately half of patients.

PMID- 22976142
TI  - Pituitary apoplexy manifesting as massive intracerebral hemorrhage. Case report.
AB  - A 68-year-old man presented with severe conscious disturbance caused by pituitary
      apoplexy resulting in massive intracerebral hemorrhage (ICH). He had been
      periodically followed up for asymptomatic pituitary adenoma at another hospital
      for 8 years. Neuroimaging examination revealed pituitary apoplexy and massive ICH
      located in the left frontal lobe, and the ICH was directly connected to the
      intratumoral hemorrhage. The diagnosis was massive ICH from pituitary apoplexy.
      The patient underwent emergent evacuation of hematoma and removal of the
      pituitary adenoma via bi-frontal craniotomy. Postoperatively, he continued to
      exhibit deep consciousness disturbance and died 1 month after the operation.
      Pituitary apoplexy is usually characterized by intra-tumoral hemorrhage. The
      treatment strategy for asymptomatic pituitary adenoma is still controversial.
      This case shows that we should always consider the risk of pituitary apoplexy
      manifesting as ICH which may cause a fatal outcome.

PMID- 22976143
TI  - Coexistence of sporadic cerebellar hemangioblastoma and pituitary null cell
      adenoma: simultaneous expression of von Hippel-Lindau gene product. Case report.
AB  - Coexistence of brain tumors of different pathologies is rare, and the majority of
      the cases were related to genetic disorders or secondary tumors occurring after
      radiotherapy. A 73-year-old man was introduced to the outpatient department
      suffering from severe nausea and vertigo. Magnetic resonance imaging showed a
      cystic tumor in the left cerebellar hemisphere and another lesion in the sella
      turcica. There was no evident family history of von Hippel-Lindau (VHL) disease,
      and the systemic investigation failed to detect any other tumors or signs of VHL
      disease. Treatment was performed in two stages, and he was discharged with
      remaining slight ataxic gait. The diagnoses were cerebellar hemangioblastoma and
      pituitary null cell adenoma. Additional immunohistochemical investigation using
      VHL disease gene-related protein in both tumors showed minute granular positive
      staining in the cytoplasm of stromal cells in the former, and diffuse and strong
      granular cytoplasmic positive staining in the latter. Further analysis is
      required to confirm the true implication of the VHL gene mutation, and the
      possible involvement of VHL gene-related protein in the pathogenesis of these
      coexisting tumors.

PMID- 22976144
TI  - Spindle cell oncocytoma of the adenohypophysis with marked hypervascularity. Case
      report.
AB  - A 68-year-old male presented with a very rare case of spindle cell oncocytoma
      (SCO), a recently identified very rare neoplasm of the anterior pituitary,
      manifesting as panhypopituitarism and visual field defect. The pituitary tumor
      with suprasellar extension was only partially resected via transsphenoidal
      surgery because of the tumor consistency and bleeding. Histological diagnosis was
      consistent with schwannoma. The tumor regrew and angiography revealed
      hypervascularity, so a transcranial approach was employed for the re-operation
      which only achieved partial resection because of intraoperative extensive
      bleeding. The tumor cells showed similar histological and immunohistochemical
      profiles to the previous specimen, but electron microscopy demonstrated that
      cytoplasm abundantly filled with mitochondria. The final diagnosis of SCO was
      established and the patient received postoperative conventional radiation therapy
      of 50 Gy. Only 15 cases of SCO have been reported, and the diagnosis was mistaken
      in many cases as schwannoma, oncocytic pituitary adenoma, or craniopharyngioma,
      and multiple surgeries followed by radiation therapy were required.

PMID- 22976145
TI  - Inflammatory pseudotumor in the lateral ventricle. Case report.
AB  - A 15-year-old boy was referred to our hospital with a rare case of inflammatory
      pseudotumor (IP) in the lateral ventricle manifesting as complaints of headache
      and low-grade fever. Computed tomography and magnetic resonance imaging
      demonstrated a well-demarcated and enhanced tumorous lesion in the right lateral
      ventricle. Intraoperative findings showed a hard mass with feeding arteries from
      the choroid plexus around the foramen of Monro in the right lateral ventricle,
      although the mass was not attached to the wall of the lateral ventricle. The
      lesion was totally resected, and the histopathological diagnosis was IP. The
      present and previous cases suggest that good outcomes are obtained by surgical
      removal and treatment of hydrocephalus. IP should be considered in the
      differential diagnosis of hard tumorous lesions with good enhancement and no
      tumorous staining in the ventricle.

PMID- 22976146
TI  - Periventricular intraparenchymal schwannoma. Case report.
AB  - A 60-year-old male presented with a rare case of periventricular schwannoma.
      Imaging studies revealed a partially calcified, well-enhanced tumor in the
      periventricular area of the left frontal horn. The preoperative diagnosis was low
      grade glioma, but postoperative pathological findings revealed that the tumor was
      schwannoma. Most intraparenchymal schwannomas are benign, so total extirpation is
      usually curative. However, this uncommon neoplasm is difficult to distinguish
      from mimics, especially low grade gliomas, with only preoperative radiological
      findings or intraoperative pathological findings. Based on our experience and
      analysis of the characteristic radiological and pathological features in previous
      cases, we suggest that an accurate intraoperative diagnosis is possible. The key
      element is the combination of correct interpretation of the intraoperative
      pathology analysis and careful evaluation of the preoperative radiological
      studies. An appropriate intraoperative judgment is important, because the
      treatment, including the surgical management, would be totally different for
      schwannoma and glioma.

PMID- 22976147
TI  - Tuberculum sellae meningioma causing progressive visual impairment during
      pregnancy. Case report.
AB  - A 29-year-old woman in the 17th week of pregnancy presented with blurred vision
      and visual impairment of both eyes. Magnetic resonance imaging revealed a
      tuberculum sellae meningioma. Visual impairment progressively worsened, and
      surgical resection was performed in the 19th week of pregnancy without fetal
      heart monitoring. The intra- and postoperative courses were without
      complications. Her visual acuity and field almost fully recovered immediately
      after the operation. She delivered a healthy normal baby on the expected day.

PMID- 22976148
TI  - Clinical, histological, and genetic features of fourth ventricle ependymoma in
      the elderly. Case report.
AB  - A 71-year-old woman presented with a rare case of geriatric ependymoma
      originating from the fourth ventricle manifesting as progressive gait and memory
      disturbance. Imaging studies revealed an extraaxial mass in the fourth ventricle
      protruding into the right cerebellomedullary cistern, with concomitant
      obstructive hydrocephalus. Surgery achieved subtotal removal since the tumor
      tightly adhered to the right vestibular area of the fourth ventricular floor. The
      histological diagnosis was ependymoma, which was also confirmed by comparative
      genetic hybridization. Although she developed severe laryngeal edema and
      worsening of the hydrocephalus postoperatively which required additional
      treatment, she recovered with residual mild gait disturbance, and was transferred
      to a rehabilitation facility. Fourth ventricle ependymoma in the elderly is rare.
      Comparative genetic hybridization may be important in the diagnosis of geriatric
      ependymoma and in the choice for adjuvant therapy as well as in estimating the
      prognosis for patients with rare types of ependymoma.

PMID- 22976149
TI  - Endoscopic biopsy for lesions located in the parenchyma of the brain:
      preoperative planning based on stereotactic methods. Technical note.
AB  - Endoscope biopsy guided navigation for intra-parenchymal lesions is safe and
      effective, but determination of the entry point and trajectory of the endoscopic
      biopsy is less clear. We describe preoperative planning based on stereotactic
      methods, and achieving the plan using several techniques. The preoperative
      planning was based on stereotactic methods such as determining target, entry
      point, and trajectory. A transparent sheath was advanced under guidance of the
      navigation system and specimens collected under visual endoscopic monitoring.
      After collecting specimens, intraoperative magnetic resonance imaging was
      performed for confirming accurate sampling. Correct specimens were obtained in 6
      cases as confirmed by intraoperative magnetic resonance imaging. The histological
      diagnoses were diffuse large B-cell type malignant lymphoma (n = 3), astrocytoma
      (n = 1), glioblastoma (n = 1), and inflammatory changes without neoplastic cells
      (n = 1). No postoperative intracranial hemorrhage or other operative
      complications occurred. Preoperative planning based on stereotactic methods and
      procedures guided by navigation systems can achieve endoscopic biopsy for
      intraparenchymal lesions safely and accurately.

PMID- 22976150
TI  - To the editor. Diffusion tensor imaging of idiopathic normal pressure
      hydrocephalus: a voxel-based fractional anisotropy study.

PMID- 22976153
TI  - The addiction concept and technology: diagnosis, metaphor, or something else? a
      psychodynamic point of view.
AB  - Many today suffer from an imbalance between life and life on the screen. When
      extreme, such as excessive gaming, clinicians retreat to familiar explanations,
      such as "Internet addiction." But the addiction concept is of limited value,
      limiting both research and treatment options. This article discusses an
      alternative. Pathological overuse is seen as a failed solution in which people
      become entrapped by technology's promise of delivering that which only life can
      offer, such as the grand adventure simulated in World of Warcraft. A two-part
      treatment approach of such "simulation entrapment" is described in which both the
      original problem and the entrapment are treated, the former by traditional
      psychodynamic psychotherapy and the later by highlighting differences between the
      technologically mediated experience and traditional experiences of being bodies
      together. The case of a college student suffering from pathological shame with
      excessive gaming as the failed solution is offered as an illustration.

PMID- 22976154
TI  - Biocompatible magnetic liposomes for temperature triggered drug delivery.
AB  - Thermosensitive magnetic liposomes (TSMLs) that serve as carriers for controlled
      drug release are fabricated. The TSMLs are stable below 39  degrees C and most
      drugs (5-(and-6)-carboxylfluorescein: 68% and doxorubicin: 90%) release within 1
      h at 42  degrees C. Furthermore, TSMLs could deliver the anticancer drugs into
      cells to induce cell apoptosis.

PMID- 22976155
TI  - Comparing responsiveness of the quick disabilities of the arm, shoulder, and hand
      and the upper limb functional index.
AB  - OBJECTIVE: The purpose of this study was to measure clinical change in persons
      with upper extremity (UE) musculoskeletal conditions and to determine if the
      Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) or the Upper Limb
      Functional Index (ULFI) was a more responsive outcome tool. The objective was to
      select one tool that was responsive and practical for the occupational therapy
      (OT) setting. PARTICIPANTS: Participants were patients (N=27) who had
      musculoskeletal conditions, were age 18 years or older, and received outpatient
      OT. METHODS: Participants received standard OT treatment for UE musculoskeletal
      conditions, completing the ULFI and QuickDASH at evaluation and discharge.
      RESULTS: Paired t-tests showed significant change of 25.1 points in the QuickDASH
      and 23.6 points in the ULFI. Work module showed significant change of 26.2
      points. CONCLUSIONS: The QuickDASH was a more responsive tool compared to the
      ULFI. Participants made significant improvements in work performance as measured
      by the QuickDASH Work Module. Large effect sizes and standardized response means
      of the QuickDASH and the ULFI change scores showed both tools were responsive
      outcome measures for individuals with musculoskeletal conditions. Although the
      QuickDASH was more responsive, therapists preferred the ULFI as an efficient
      outcome measure with client-centered goals.

PMID- 22976156
TI  - Work-related musculoskeletal disorders among Iranian dentists.
AB  - OBJECTIVE: To evaluate musculoskeletal disorders (MSDs), associated factors and
      treatment among dentists over a one year period. METHOD: A total of 272
      questionnaires were returned complete providing demographic information, details
      of the physical workload, location of pain in the body, and the treatment and
      prevention of MSDs. All data was coded for each of the parameters. The
      association between pain and each of the parameters was determined by parametric
      and non-parametric statistical tests (P < 0.05). PARTICIPANTS: General and
      specialist dentists participated in the study. The sample set of dentists
      consisted of 205 (75.4%) generalists and 67 (24.6%) specialists. RESULTS: Seventy
      five percent of the total cohort experienced MSDs. Female dentists complained of
      pain significantly more frequently than their male counterparts (p=0.018).
      Significantly higher rates of pain and MSDs are related to increased years of
      work (r=0.168, p =0.017) and less regular ergonomic exercise (p=0.002). Reported
      pain was most common in the shoulder (44.2%), neck (31.8%) and lower back
      (29.9%). Dentists who worked inclined had significantly more pain disorder than
      those who did not (p=0.013). In total 23.5% of dentists reduced working hours and
      16.5% sought medical help. CONCLUSION: Pain was most commonly reported in the
      shoulder, neck and back. Physical workload is an important factor in MSDs. The
      impact of MSDs on the work and life of dentists demonstrates the need for
      increased knowledge of MSDs and the instigation of preventive strategies.

PMID- 22976157
TI  - How important are human immunodeficiency virus (HIV) clinical markers to the long
      term formal employment among people living with HIV in developing countries? A
      study in South Africa.
AB  - OBJECTIVE: To examine the relationship of Human Immunodeficiency Virus (HIV)
      clinical markers and socio-demographic characteristics with long-term formal
      employment among people living with HIV (PLHIV). PARTICIPANTS: 554 adults, 55%
      females, on HIV treatment for at least two years at two public hospitals in
      Johannesburg, South Africa. METHODS: A retrospective cohort design, tracing
      changes in study participants' formal employment status since the first HIV
      positive diagnosis. Data collection included historical medical records review
      and interviewer-administered questionnaires. RESULTS: 44% of all study
      participants (39% and 49% among males and females, respectively) were formally
      employed at the time of the study, primarily in low-skilled jobs in the private
      sector. The majority (83%) of males and 60% of females remained in formal
      employment since being diagnosed as HIV-positive. Female gender, education to
      grade 12 or higher, a smaller household size and being married were significantly
      associated with current formal employment. Formal employment was unrelated to HIV
      treatment indicators (CD4 count, viral load and duration since diagnosis). Of
      those in formal employment, 68 (28%) were aware of HIV policies at their
      workplaces, which was also positively associated with the duration in their
      current employment. CONCLUSIONS AND RECOMMENDATIONS: PLHIV in developing country
      contexts can enter into and maintain formal employment, especially when treatment
      and workplace support are available. Thus, employer organisations should
      implement effective workplace HIV policies to enhance employment experiences of
      their workforce living with HIV. Care and support services for people on HIV
      treatment should also address their career development needs.

PMID- 22976158
TI  - Eye problems among the workers in re-rolling mill exposed to high temperature.
AB  - OBJECTIVE: The aim of the study was to find out the eye problems of the workers
      exposed to high temperature in re-rolling mill. PARTICIPANTS: A cross sectional
      study was conducted among 200 workers of selected re-rolling mills in Chittagong
      of Bangladesh during April to June 2008. METHODS: Data was collected through face
      to face interview of the respondents by using a pre tested questionnaire and
      check list and physical examinations which were completed by Braun Thermo Scan
      Ear Thermometer and by Coaxial-plus Ophthalmoscope. Work place temperature and
      humidity were measured by industrial digital thermometer and hygrometer. RESULTS:
      Physical examination revealed that 25.5% of participants had inflammation of
      conjunctiva, 26% had itching of the eyes, 1.5% had corneal inflammation, 13.5%
      had partial opacity of the cornea, and 20.5% had hazy corneas. Of the total
      respondents, a majority had redness of the eyes, itching and blurring of vision.
      Most of the complaints were found to be associated with longer job duration (>= 5
      years), production workers and high temperature (>= 40 degrees C). CONCLUSION:
      The current study findings recommended that, the workers should be protected by
      using safety glasses with side shields and by wearing an apron of impervious
      cloth. There should be a surveillance system on work environments by appropriate
      authority for monitoring safety and maintenance of industrial hygiene.

PMID- 22976159
TI  - Organizational factors related to low levels of sickness absence in a
      representative set of Swedish companies.
AB  - OBJECTIVE: The aim of this qualitative study was to identify manageable
      organizational factors that could explain why some companies have low levels of
      sickness absence. There may be factors at company level that can be managed to
      influence levels of sickness absence, and promote health and a prosperous
      organization. PARTICIPANTS: 38 representative Swedish companies. METHODS: The
      study included a total of 204 semi-structured interviews at 38 representative
      Swedish companies. Qualitative thematic analysis was applied to the interviews,
      primarily with managers, to indicate the organizational factors that characterize
      companies with low levels of sickness absence. RESULTS: The factors that were
      found to characterize companies with low levels of sickness absence concerned
      strategies and procedures for managing leadership, employee development,
      communication, employee participation and involvement, corporate values and
      visions, and employee health. CONCLUSIONS: The results may be useful in finding
      strategies and procedures to reduce levels of sickness absence and promote
      health. There is research at individual level on the reasons for sickness
      absence. This study tries to elevate the issue to an organizational level. The
      findings suggest that explicit strategies for managing certain organizational
      factors can reduce sickness absence and help companies to develop more health
      promoting strategies.

PMID- 22976160
TI  - Innovative assistive technology in Finnish public elderly-care services: a focus
      on productivity.
AB  - OBJECTIVE: The study investigates ways in which technology use may help
      municipalities improve productivity in elderly-care services. A case study of
      Finnish elderly-care services provides responses concerning impacts, decisions
      and options in technology use. METHODS: The research data were collected during a
      'smart home pilot' implemented in four housing service units. Over 60 assistive
      devices were introduced in the smart homes used during short-term housing
      periods. PARTICIPANTS: Both customers and care staff's experiences as well as
      processes related to the use of assistive devices were investigated on the basis
      of survey questionnaires, interviews and feedback. RESULTS: Assistive device
      related operational processes were investigated with the help of concepts of
      'resource focus', 'lost motion' and 'intermediate storage'. Four central
      operational processes were identified. Design and desirability as well as costs,
      such as opportunity costs of assistive devices were also a focus. Significant
      factors related to productivity were disclosed in this way. CONCLUSIONS:
      Technology use versus productivity needs to be 'circled' from the points of view
      of individual users, workplaces, service processes, and larger technology
      options. There must be long-term patience to introduce technology properly into
      use to produce positive impacts on productivity. Customers and care staff have an
      interlinked, vital role to play as decision-makers' informants.

PMID- 22976161
TI  - Perceptions of the worker role among people with psychiatric disabilities:
      description and investigation of associated factors.
AB  - OBJECTIVE: To investigate how subjective perceptions of everyday occupations,
      activity level, day centre attendance, social interaction, self-mastery and
      clinical factors were related to how unemployed people with psychiatric
      disabilities (PD) envision a future worker role, also controlling for socio
      demographic variables. PARTICIPANTS: 175 people with PD; 93 attended a day centre
      and 82 did not. Of the 93 day centre attendees 39 visited meeting place-oriented
      day centres and 54 attended work-oriented ones. METHODS: Self-ratings and
      interview-based instruments were used to assess the view of the worker role,
      social interaction, subjective perceptions of everyday occupations, activity
      level, self-mastery, and socio-demographic and clinical factors. Non-parametric
      statistics were used when analysing the data. RESULTS: A few aspects of the
      worker role seemed positively influenced by attending a day centre, in particular
      a work-oriented one. High levels of activity (p=0.009) and self-mastery
      (p=0.024), being younger (p=0.004) and having less depression (p=0.008) were also
      associated with a more positive view of the worker role. CONCLUSION: In order to
      enhance a future worker role the individual's feeling of control in the
      rehabilitation process should be highlighted and possibilities for general
      activity engagement be offered. Since the findings indicate that most aspects of
      the worker role were not enhanced by day centre attendance community-based care
      should further concentrate on promoting this future role for people with PD.

PMID- 22976163
TI  - Ergonomic evaluation of pounding of rice with traditional tool.
AB  - Pounding of rice for the preparation of indigenous food items is a regular food
      processing activity in rural Assam. The traditional tool used by the rural women
      for pounding is called 'Dhenki'. OBJECTIVES: An attempt was made to assess
      physical fitness of participants, to determine physiological workload involved in
      pounding of rice with this traditional tool, and to ascertain muscular and
      postural stress involved in the activity. PARTICIPANTS: Twenty subjects in the
      age of 21-45 years were purposively selected. METHODS: A stepstool technique was
      adopted for assessing physical fitness of the participants. Heart rate was
      recorded with Polar Heart Rate Monitor (Polar Sports Tester - PE 4000) and angle
      of deviation in lower lumber region was measured with Dual Inclinometer during
      the operation. RESULTS: The average resting heart rate values of participants was
      80 b.min(-1). Average working heart rate values in pounding activity was 118.18
      b.min(-1) and average energy expenditure was 10.04 kJ/min. Physiological workload
      of pounding of rice on the basis of heart rate and Energy Expenditures was found
      to be 'Moderately Heavy'. Perceived exertion of participants in pounding activity
      (RPE) was rated 4.1 in 5 point scales. CONCLUSIONS: Ergonomic interventions
      through redesigning of traditional tool will improve work performance and enhance
      productivity of farm women.

PMID- 22976164
TI  - Implementation of a rehabilitation model for employees on long-term sick leave in
      the public sector: difficulties, counter-measures, and outcomes.
AB  - OBJECTIVE: The aim was threefold: 1) to describe the experiences of driving and
      implementing a workplace-based rehabilitation intervention in cooperation with
      the occupational health service (OHS); 2) to investigate which people received
      multimodal and/or vocational rehabilitation measures; 3) to find predictors of
      return to work (RTW). PARTICIPANTS: Altogether 779 employees on sick leave for 90
      days or more with mainly musculoskeletal or psychological/stress-related
      problems, 90% women. METHODS: The HAKuL model was introduced, implying an early
      team assessment at the OHS and good access to rehabilitation measures. The study
      is a prospective three-year study with a two-year follow-up. RESULTS: The
      rehabilitation intervention encountered challenges. Counter-measures were taken
      to facilitate coordination and communication. People with musculoskeletal
      problems often received both multimodal and vocational rehabilitation. Vocational
      rehabilitation was advocated for people who were under 55 years of age, and for
      those with stress-related problems. The strongest predictive factors for RTW
      were: having received only vocational rehabilitation and being under 45 years of
      age. CONCLUSION: The HAKuL model can be used in a wider context, but the study
      shows the need for coordination between multiple stakeholders. Supervisors should
      pay attention to people who have musculoskeletal problems and are older, as soon
      as problems emerge.

PMID- 22976165
TI  - Reality shock: experiences of Indian Information Technology (IT) professionals.
AB  - OBJECTIVE: The objective of the study is to analyze the relationship between the
      work expectations and experiences of employees who have joined a new organization
      and have experienced a reality shock as a result of the portrayal of a hyped
      image of the organization or work/position. It explores discrepancies in the
      employees' expectations of the world of work and the reality of the organization
      and work they experience, giving them a reality shock. PARTICIPANTS: Sixteen IT
      professionals from two different organizations participated in this study.
      METHOD: Qualitative data was obtained through in-depth interviews with sixteen
      participants employed with twodifferent organizations in western India. RESULTS:
      Discussion with the participants led to the emergence of five different types of
      shocks experienced by them. They are phony designation, the salary difference,
      accessibility of benefits, decisive culture and limited scope for career growth.
      All these shocks lead to the development of the final theme i.e. intentions to
      leave. CONCLUSIONS: Based on the study findings, there is an imperative that the
      human resource department and organizational forerunners understand the
      importance of portraying a realistic image of the organization, nature of the job
      and future career prospects and counseling to new entrants of the organization.

PMID- 22976166
TI  - The relationship between musculoskeletal symptoms, postures and the fit between
      workers' anthropometrics and their computer workstation configuration.
AB  - OBJECTIVE: Awkward postures during computer use are assumed to be related to the
      fit between the worker and the workstation configuration, with greater mismatches
      leading to higher levels of musculoskeletal symptoms (MSS). The objective of this
      study was to examine if chronic MSS of the neck/shoulder, back, and wrist/hands
      was associated with 1) discrepancies between workstation setups and worker
      anthropometrics and 2) workers' postures. PARTICIPANTS: Secondary analysis on
      data collected from a randomized controlled cross-over design trial (N=74).
      METHOD: Subjects' workstation configurations, baseline levels of MSS, working
      postures, and anthropometrics were measured. Correlations were completed to
      determine the association between postures and discrepancies between the worker
      anthropometrics and workstation configuration. Associations were examined between
      postures, workstation discrepancies and worker MSS. RESULTS: There were only 3
      significant associations between worker posture and MSS, and 3 significant
      associations between discrepancies in worker/workstation set-up and MSS.
      CONCLUSION: The relationship between chronic MSS and the workers computer
      workstation configuration is multifactorial. While postures and the fit between
      the worker and workstation may be associated with MSS, other variables need to be
      explored to better understand the phenomenon.

PMID- 22976167
TI  - Effect of an ergonomic intervention on muscle fatigue and respiratory stress of
      goldsmiths during blowing pipe activity in India.
AB  - OBJECTIVE: One of the main activities of the goldsmiths is Blowing Pipe. The
      blowpipe is to expand and shape the gold beads by means of positive pressure
      produced by careful, controlled oral expiration. Objective of this study was to
      assess the effect of ergonomic intervention on facial muscle fatigue and
      respiratory stress of goldsmiths to continue their work. PARTICIPANTS: For this
      current study 100 male goldsmiths were selected from the Davangere District of
      Karnataka. METHODS: This study used the questionnaire, Examination of Pulmonary
      Function, Measurement of peak expiratory flow rate and electromyography of three
      major facial muscles. Three primary types of ergonomic interventions were
      provided to the goldsmiths. Subjects were interviewed at the end of each week to
      ascertain intervention acceptance. From the analysis of subject's preference, the
      hand air pipe was selected by. RESULTS: A large number of goldsmiths complained
      of respiratory symptoms in this industry. Reduced lung volumes and peak
      expiratory flow rates of goldsmiths was found, presumably from heavy pressure
      generated by using blow pipe. This work habit also increases the fatigue of
      facial muscles, at the end of the day. CONCLUSION: It was found that, by
      implementing the ergonomic intervention can reduce facial muscle fatigue and
      respiratory stress of goldsmiths.

PMID- 22976168
TI  - What leads to the expectation to return to work? Insights from a Theory of
      Planned Behavior (TPB) model of future work outcomes.
AB  - OBJECTIVE: This study used a Theory of Planned Behavior (TPB) model to identify
      the factors influencing the future work expectations and outcomes of employees
      with a musculoskeletal injury. PARTICIPANTS: Australians with a compensable work
      injury (N=174), mean age=43.7 years, 53.2% male, 48.3% back injury , and 34.2%
      unskilled. METHODS: A TPB model of the target behavior 'working, or continuing to
      work ... three months from now' was constructed. A questionnaire measuring the
      model's components was completed at baseline and three-months follow-up. RESULTS:
      The model met standard psychometric requirements. Attitude, Subjective Norm and
      Perceived Behavioral Control explained 76% of the variance in Behavioral
      Intention (<formula>R^{2}</formula>= 0.76, p< 0.001). Behavioral Intention (the
      expectation to return to work) explained 51% of the variance in work
      participation at follow-up (Nagelkerke <formula>R^{2}</formula>=0.51, p< 0.001;
      sensitivity=86.4%, specificity=71.2%). The strength of key influences on
      expectations varied according to employment status, but included the availability
      of modified duties, social aspects of work, the opinion of the treating doctor,
      co-worker support, pain, and functional limitations. CONCLUSION: The TPG is a
      useful model and conceptual framework for integrating the biopsychosocial
      determinantsof return to work (RTW) and identifying the influences on future work
      expectations and outcomes.

PMID- 22976169
TI  - Calcium carbonate nanotablets: bridging artificial to natural nacre.
AB  - Single-crystalline CaCO(3) nanotablets are synthesized in large quantities
      through oriented attachment of pristine nanoparticles. The prepared nanotablets
      can serve as genuine building blocks for the construction of nacreous inorganic
      organic hybrids, through which freestanding films and monoliths with tunable
      composition and mechanical properties are fabricated. These newly available
      CaCO(3) crystal tablets may also serve as a starting platform for future CaCO(3)
      research.

PMID- 22976171
TI  - Intra-flap thrombosis secondary to acute sickle crisis: a case report.
AB  - We present the case of a 40-year-old patient with sickle cell trait who underwent
      bilateral breast reconstruction with microvascular TRAM flap transfer.
      Intraoperatively, the patient developed arterial anastomotic thrombosis of the
      right breast flap. The left breast flap had already been harvested and was placed
      on ice. Both anastomoses were then successfully completed. Postoperatively, the
      patient developed a pulmonary embolism and heparin-induced thrombocytopenia. On
      postoperative day 12, the left cutaneous Doppler signals were lost, and
      exploration revealed a thrombosed pedicle and nonviable left breast flap.
      Pathologic specimen evaluation revealed sickled cells within the flap
      microvasculature. We believe that prolonged ischemia time and hypothermia
      precipitated erythrocyte sickling within the flap, causing intra-flap thrombosis
      that propagated to the pedicle. While sickle cell diseases are not a
      contraindication to free tissue transfer, we believe that flap cooling should be
      utilized with caution in this circumstance.

PMID- 22976170
TI  - Synergistic anticancer activities of the plant-derived sesquiterpene lactones
      salograviolide A and iso-seco-tanapartholide.
AB  - We have previously shown that the two sesquiterpene lactones, salograviolide A
      (Sal A) and iso-seco-tanapartholide (TNP), isolated from the Middle Eastern
      indigenous plants Centaurea ainetensis and Achillea falcata, respectively,
      possess selective antitumor properties. Here, we aimed to assess the anticancer
      effects of the separate compounds and their combination, study their potential to
      generate reactive oxygen species (ROS), and investigate their underlying
      antitumor mechanisms in human colon cancer cell lines. Cells were treated with
      Sal A and TNP alone or in combination, and cell viability, cell cycle profile,
      apoptosis, ROS generation and changes in protein expression were monitored. Sal A
      and TNP in combination caused 80% decrease in HCT-116 and DLD-1 cell viability
      versus only 25% reduction when the drugs were used separately. The antitumor
      mechanism involved triggering ROS-dependent apoptosis as well as disruption of
      the mitochondrial membrane potential. Further studies showed that apoptosis by
      the Sal A and TNP combination was caspase-independent and that ERK, JNK and p38
      of the serine/threonine MAPKs signaling pathway were involved in the cell death
      mechanism. Taken together, our data suggest that the combination of Sal A and TNP
      may be of therapeutic interest against colon cancer.

PMID- 22976172
TI  - Prosocial attitudes and empathic behavior in emotional positive versus negative
      situations: brain response (ERPs) and source localization (LORETA) analysis.
AB  - The present research firstly investigated the neural correlates (ERPs, event
      related potentials) of attitudes to engage in prosocial-helping behaviors, and
      secondly, it analyzed the relation between these brain-based potentials and
      personal profile (high vs. low empathic profile). It was considered the subjects'
      behavior in response to specific emotional situations (positive vs. negative) in
      case it was required a possible prosocial intervention. Thirty-one subjects were
      invited to empathize with the emotional contexts (videotapes that reproduced two
      person's exchanges) and to decide whether to intervene or not to support these
      persons. BEES questionnaire for empathic behavior was submitted to the subjects
      after the experimental session. ERP acquisition and LORETA source analysis
      revealed a negative ongoing deflection (N200 effect) more prefrontally
      distributed (dorsolateral prefrontal cortex) in response to prosocial
      intervention options mainly for negative and positive contexts. Moreover, a
      significant positive correlation was found between high-empathic profiles,
      intervention behaviors (higher frequency of interventions) and N200 amplitude
      (higher peak). These results highlight the role of emotions in prosocial
      behavior, since the N200 effect was considered a marker of the emotional
      significance of the interpersonal situation. Secondly, the empathic trait may
      explain the prosocial decisional processes: Higher empathic trait contributes to
      induce subject's intervention behavior which in turn appears to be directly
      related to the cortical responsiveness within the prefrontal areas.

PMID- 22976173
TI  - Use of partial area under the curve metrics to assess bioequivalence of
      methylphenidate multiphasic modified release formulations.

PMID- 22976174
TI  - Functions of single-strand DNA-binding proteins in DNA replication,
      recombination, and repair.
AB  - Double-stranded (ds) DNA contains all of the necessary genetic information,
      although practical use of this information requires unwinding of the duplex DNA.
      DNA unwinding creates single-stranded (ss) DNA intermediates that serve as
      templates for myriad cellular functions. Exposure of ssDNA presents several
      problems to the cell. First, ssDNA is thermodynamically less stable than dsDNA,
      which leads to spontaneous formation of duplex secondary structures that impede
      genome maintenance processes. Second, relative to dsDNA, ssDNA is hypersensitive
      to chemical and nucleolytic attacks that can cause damage to the genome. Cells
      deal with these potential problems by encoding specialized ssDNA-binding proteins
      (SSBs) that bind to and stabilize ssDNA structures required for essential genomic
      processes. SSBs are essential proteins found in all domains of life. SSBs bind
      ssDNA with high affinity and in a sequence-independent manner and, in doing so,
      SSBs help to form the central nucleoprotein complex substrate for DNA
      replication, recombination, and repair processes. While SSBs are found in every
      organism, the proteins themselves share surprisingly little sequence similarity,
      subunit composition, and oligomerization states. All SSB proteins contain at
      least one DNA-binding oligonucleotide/oligosaccharide binding (OB) fold, which
      consists minimally of a five stranded beta-sheet arranged as a beta barrel capped
      by a single alpha helix. The OB fold is responsible for both ssDNA binding and
      oligomerization (for SSBs that operate as oligomers). The overall organization of
      OB folds varies between bacteria, eukaryotes, and archaea. As part of SSB/ssDNA
      cellular structures, SSBs play direct roles in the DNA replication,
      recombination, and repair. In many cases, SSBs have been found to form specific
      complexes with diverse genome maintenance proteins, often helping to recruit
      SSB/ssDNA-processing enzymes to the proper cellular sites of action. This
      clustering of genome maintenance factors can help to stimulate and coordinate the
      activities of individual enzymes and is also important for dislodging SSB from
      ssDNA. These features support a model in which DNA metabolic processes have
      evolved to work on ssDNA/SSB nucleoprotein filaments rather than on naked ssDNA.
      In this volume, methods are described to interrogate SSB-DNA and SSB-protein
      binding functions along with approaches that aim to understand the cellular
      functions of SSB. This introductory chapter offers a general overview of SSBs
      that focuses on their structures, DNA-binding mechanisms, and protein-binding
      partners.

PMID- 22976175
TI  - Structural diversity based on variability in quaternary association. A case study
      involving eubacterial and related SSBs.
AB  - Eubacterial and related single-stranded DNA-binding proteins (SSBs) exhibit
      considerable variability in their quaternary association in spite of their having
      the same tertiary fold. The variability involves differences in the orientation
      of dimers in the tetrameric molecule (or of two-domain subunits in the dimeric
      molecule) and that of monomers in each dimer. The presence of an additional
      strand in mycobacterial and related SSBs, which clamps the dimers together, is a
      major determinant of the mode of quaternary association in them. The variability
      in quaternary structure has implications to the stability of the protein and
      possibly to its mode of DNA binding.

PMID- 22976176
TI  - SSB binding to ssDNA using isothermal titration calorimetry.
AB  - Isothermal titration calorimetry (ITC) is a powerful method for studying protein
      DNA interactions in solution. As long as binding is accompanied by an appreciable
      enthalpy change, ITC studies can yield quantitative information on
      stoichiometries, binding energetics (affinity, binding enthalpy and entropy) and
      potential site-site interactions (cooperativity). This can provide a full
      thermodynamic description of an interacting system which is necessary to
      understand the stability and specificity of protein-DNA interactions and to
      correlate the activities or functions of different species. Here we describe
      procedures to perform and analyze ITC studies using as examples, the E. coli SSB
      (homotetramer with 4 OB-folds) and D. radiodurans SSB (homodimer with 4 OB
      folds). For oligomeric protein systems such as these, we emphasize the need to be
      aware of the likelihood that solution conditions will influence not only the
      affinity and enthalpy of binding but also the mode by which the SSB oligomer
      binds ssDNA.

PMID- 22976177
TI  - SSB-DNA binding monitored by fluorescence intensity and anisotropy.
AB  - Fluorescence methods have proven to be extremely useful tools for quantitative
      studies of the equilibria and kinetics of protein-DNA interactions. If the
      protein contains tryptophan (Trp), as is often the case, and there is a change in
      intrinsic Trp fluorescence of the protein, one can use this change in signal
      (quenching/enhancement) to monitor binding. One can also attach an extrinsic
      fluorophore to either the protein or the DNA and monitor binding due to a change
      in fluorescence intensity or a change in fluorescence anisotropy. Such
      equilibrium studies can provide important quantitative information on
      stoichiometries (occluded site size, number of binding sites) and energetics
      (affinities and cooperativities) of the interactions. This information is needed
      to understand the mechanisms of protein-DNA interactions. A critical aspect of
      such approaches for systems that have non-unity stoichiometries (e.g., a protein
      that binds multiple ligands) is knowledge of the relationship between the change
      in fluorescence signal (intensity or anisotropy) and the average extent of
      binding. Here we describe procedures for using fluorescence approaches to examine
      the stoichiometries and equilibrium binding affinities of Escherichia coli single
      stranded DNA-binding protein (SSB) and Deinococcus radiodurans SSB with long
      polymeric ssDNA to determine an occluded site size. We also provide examples of
      studies of SSB binding to shorter oligonucleotides to demonstrate analysis and
      fitting of the data to an appropriate model (monitoring fluorescence intensity or
      anisotropy) to obtain quantitative estimates of equilibrium binding parameters.
      We emphasize that the solution conditions (especially salt concentration and
      type) can influence not only the binding affinity, but also the mode by which an
      SSB oligomer binds ssDNA.

PMID- 22976178
TI  - Single-molecule analysis of SSB dynamics on single-stranded DNA.
AB  - SSB proteins bind to and control the accessibility of single-stranded (ss) DNA
      generated as a transient intermediate during a variety of cellular processes. For
      subsequent DNA processing, however, SSB needs to be removed and yield to other
      proteins while avoiding ssDNA exposure to nucleases. Using single-molecule two-
      and three-color fluorescence resonance energy transfer (FRET) and fluorescence
      force spectroscopy, we recently showed that the SSB/DNA complex is a highly
      dynamic system and SSB functions as a sliding platform that migrates on ssDNA for
      recruiting other proteins in DNA repair, replication, and recombination. Here, we
      present the activity assays in detail for observing the transitions between
      different SSB binding modes and SSB diffusion on ssDNA in real time by using
      single-molecule FRET microscopy and for studying how mechanical forces regulate
      SSB-DNA interactions using fluorescence-force spectroscopy. These single-molecule
      approaches are generally applicable to many other protein-nucleic acid systems.

PMID- 22976179
TI  - Sample preparation methods to analyze DNA-induced structural changes in
      replication protein A.
AB  - Propagation and maintenance of the cellular genome are among the most fundamental
      cellular processes, encompassing pathways associated with DNA replication, damage
      response, and repair. Replication Protein A (RPA), the primary single-stranded
      DNA-binding protein (SSB) in eukaryotes, serves to protect ssDNA generated during
      these events and to recruit and organize other DNA-processing factors requiring
      access to ssDNA substrates. RPA engages ssDNA in distinct, progressive binding
      modes, which are thought to correspond to different functional states of the
      protein during the course of DNA processing. Structural characterization of these
      unique complexes has remained challenging, however, as RPA is a multi-domain
      protein characterized by a flexible, modular organization. Biophysical approaches
      that are well suited to probing time-varying architectures, such as NMR and small
      angle X-ray and neutron scattering (SAXS/SANS), when integrated with
      computational methods, can provide critical insights into the architectural
      changes associated with RPA's different DNA-binding modes. The success of these
      methods, however, is highly contingent upon the purity, homogeneity, and
      stability of the sample under study. Here we describe a basic protocol for
      characterizing and optimizing sample conditions for RPA/ssDNA complexes prior to
      study by SAXS and/or SANS.

PMID- 22976180
TI  - Structural studies of SSB interaction with RecO.
AB  - Interaction of recombination protein RecO with single-stranded (ss) DNA-binding
      protein (SSB) is essential for DNA damage repair and restart of stalled
      replication (Cox, Crit Rev Biochem Mol Biol 42(1):41-63, 2007). To understand
      mechanism of this interaction and its role in DNA repair, we deciphered a high
      resolution structure of RecO complex with C-terminal tail of SSB (SSB-Ct). The
      structure revealed a key role of hydrophobic interactions between two proteins
      and suggests the mechanism of RecO recruitment to DNA during homologous
      recombination and strand annealing.

PMID- 22976181
TI  - Investigation of protein-protein interactions of single-stranded DNA-binding
      proteins by analytical ultracentrifugation.
AB  - Bacterial single-stranded DNA-binding (SSB) proteins are essential for DNA
      metabolism, since they protect stretches of single-stranded DNA and are required
      for numerous crucial protein-protein interactions in DNA replication,
      recombination, and repair. At the lagging strand of the DNA replication fork of
      Escherichia coli, for example, SSB contacts not only DnaG primase but also the
      chi subunit of DNA polymerase III, thereby facilitating the switch between
      primase and polymerase activity. Here, we describe a powerful method that allows
      the study of interactions between SSB and its binding partners by sedimentation
      velocity experiments in an analytical ultracentrifuge. Whenever two molecules
      interact, a complex of a higher mass forms that can usually be distinguished from
      free binding partners by its different sedimentation behavior. As an example, we
      show how sedimentation velocity experiments of purified proteins can be employed
      to determine the binding parameters of the interaction of SSB and the chi subunit
      of DNA polymerase III from E. coli.

PMID- 22976182
TI  - Ammonium sulfate co-precipitation of SSB and interacting proteins.
AB  - Bacterial single-strand DNA-binding protein (SSB) interacts with many proteins
      involved in the diverse process of genome maintenance. The interactions are
      mediated by the essential and conserved amphipathic C-terminus (SSB-Ct). SSB
      plays a critical role in localizing and stimulating the activity of a wide
      variety of DNA-processing proteins. The interaction partners have been identified
      and studied using a variety of methods, one of which, ammonium sulfate co
      precipitation, is described here.

PMID- 22976183
TI  - Analyzing interactions between SSB and proteins by the use of fluorescence
      anisotropy.
AB  - Fluorescence anisotropy is a useful tool to detect SSB interaction with SSB
      binding partners. Titrating an SSB protein partner into a solution containing
      fluorescently labeled SSB C-terminal tail (SSB-Ct) peptide results in formation
      of the protein complex with molecular weights greatly higher than SSB peptide
      alone. Thus the tumbling of the complexes in solution is slower, and the
      fluorescence anisotropy (FA) signal would be increased, indicating the binding.
      Based on the FA binding curve, the apparent dissociation constant (K(d,app)) of
      the binding reaction can also be calculated.

PMID- 22976184
TI  - Far Western blotting as a rapid and efficient method for detecting interactions
      between DNA replication and DNA repair proteins.
AB  - Protein-protein interactions are required for the proper function of many
      biological pathways. Numerous biochemical and protein blotting methods are
      available for probing direct and indirect interactions between two protein
      binding partners. Here, we describe the methodology of far Western blotting, or
      immunodot blotting, as a technique for probing direct interactions between two
      proteins. We describe the utility of this approach as a rapid, qualitative screen
      for identifying novel protein-binding partners. We also describe the importance
      of this technique for measuring differences in interaction between wild-type and
      mutant forms of a known binding partner. Far Western blotting is a rapid and
      highly reproducible experimental approach for identifying and understanding the
      interaction between protein-binding partners leading to new discoveries in the
      function and regulation of biological pathways.

PMID- 22976185
TI  - Methods for analysis of SSB-protein interactions by SPR.
AB  - Surface plasmon resonance (SPR) is a widely employed technique for studying
      protein-protein interactions. Here, we describe a method for the analysis of
      single-stranded DNA binding protein (SSB)-heterologous protein interactions by
      SPR. This method avoids several pitfalls often associated with SPR, particularly
      difficulties in immobilizing the protein while still allowing for facile
      regeneration of the sensor chip surface for subsequent experiments. Essentially,
      the method entails immobilizing a biotinylated single-stranded DNA oligo onto the
      chip surface, which is then bound by SSB prior to analyte addition to the SSB
      coated chip. This allows for rapid qualitative and detailed quantitative analysis
      of both equilibrium and kinetic parameters of the SSB-protein interaction.

PMID- 22976186
TI  - Use of native gels to measure protein binding to SSB.
AB  - We describe a procedure to detect protein binding to SSB by polyacrylamide gel
      electrophoresis under non-denaturing conditions. As an example, we show the
      interaction of Thermus thermophilus (Tth) SSB with its cognate RecO protein. The
      interaction is detected as decay of the band corresponding to SSB by addition of
      RecO. We also demonstrate analysis of the RecO-RecR interaction as another
      example of this method.

PMID- 22976187
TI  - Identification of small molecules that disrupt SSB-protein interactions using a
      high-throughput screen.
AB  - Bacterial single-stranded DNA-binding proteins (SSBs) recruit a diverse array of
      genome maintenance enzymes to their sites of action through direct protein
      interactions. The essential nature of these SSB-protein interactions makes
      inhibitors that block SSB-partner complex formation valuable biochemical tools
      and attractive potential antibacterial agents. However, many of these protein
      protein interactions are weak and not amenable to the high-throughput nature of
      small molecule screens. Here I describe a high-throughput screen to identify
      small molecules that inhibit the interaction between Exonuclease I (ExoI) and the
      final 10 amino acids of the SSB C-terminal tail (SSB-Ct). The strength of the
      binding between ExoI and the SSB-Ct tail is fundamental to the interaction's
      utility in the high-throughput screen.

PMID- 22976188
TI  - Detection of posttranslational modifications of replication protein A.
AB  - Replication Protein A (RPA) is a single-strand DNA-binding protein that is found
      in all eukaryotes. RPA is subjected to multiple posttranslational modifications
      including serine- and threonine-phosphorylation, poly-ADP ribosylation, and
      SUMOylation. These modifications are believed to regulate RPA activity through
      modulating interactions with DNA and partner proteins. This article describes two
      methods used to detect posttranslational modified RPA: immunofluorescence and
      immmuoblotting.

PMID- 22976189
TI  - Detecting posttranslational modifications of bacterial SSB proteins.
AB  - Posttranslational modifications of single-stranded DNA-binding proteins (SSBs),
      which are essential proteins in DNA metabolism, have been reported from
      prokaryotic to eukaryotic systems. While eukaryotic SSBs are regulated by
      phosphorylation on serine and threonine residues, bacterial SSB proteins are also
      phosphorylated on tyrosine residues. This was initially observed during a
      systematic search for global phosphotyrosine-containing proteins in Streptomyces,
      complex life cycle bacteria that support mycelial growth and spore formation.
      Tyrosine phosphorylation was further confirmed on SSB proteins from the spore
      forming bacterium Bacillus subtilis and in the simpler prokaryote, Escherichia
      coli. However, a thorough study of this modification and its cognate kinase has
      been performed only on SSB proteins from Bacillus subtilis. It was shown that
      phosphorylation of B. subtilis SSB (SsbA) significantly increases binding
      affinity with single-stranded DNA in vitro. Mass spectrometry analysis of SsbA
      identified Tyr82 as the phosphorylation site. Analyses of the resolved and
      predicted crystal structures of SSB proteins from B. subtilis, E. coli, and S.
      coelicolor revealed that the Tyr phosphorylation site occupies similar positions
      in all three structures. Our results indicate that tyrosine phosphorylation of
      bacterial SSBs is a conserved modification in taxonomically distant bacteria.

PMID- 22976190
TI  - Fluorescent SSB as a reagentless biosensor for single-stranded DNA.
AB  - Helicases are an important and much studied group of enzymes that generally
      couple ATP hydrolysis to the separation of strands of base-paired nucleic acids.
      Studying their biochemistry at different levels of organization requires assays
      that measure the progress of the reaction in different ways. One such method
      makes use of the single-stranded DNA-binding protein (SSB) from Escherichia coli.
      This is used as a protein framework to produce a "reagentless biosensor," making
      use of its tight and specific binding of single-stranded DNA. The attachment of a
      fluorophore to this protein produces a signal in response to that binding. Thus
      the (G26C)SSB, labeled with a diethylaminocoumarin, gives a ~5-fold fluorescence
      increase on binding to single-stranded DNA and this can be used to assay the
      progress of helicase action along double-stranded DNA. A protocol for this is
      described along with a variant that can be used to follow the unwinding on a
      single molecule scale.

PMID- 22976191
TI  - Fluorescent single-stranded DNA-binding proteins enable in vitro and in vivo
      studies.
AB  - Fluorescent single-stranded DNA-binding proteins (SSB) that have a defined number
      of fluorophores per tetramer are invaluable tools to understand biochemical
      mechanism and biological function. Here, we describe the purification of
      fluorescent SSB chimeras with a unique number of fluorescent subunits
      incorporated per tetramer. We describe the use of these tetramers to enable clear
      visualization of SSB in vivo. Purified chimeras also facilitate single molecule
      studies (Liu et al., Protein Sci 20:1005-1020, 2011).

PMID- 22976192
TI  - Use of fluorescently tagged SSB proteins in in vivo localization experiments.
AB  - The time and place of DNA replication in cells provides invaluable insight into
      the cell cycle and DNA metabolism. An effective means of obtaining this
      information is through fluorescence microscopy. The abundance of Single-Strand
      Binding protein, SSB, at the replication fork makes it a good reporter of DNA
      replication. In this chapter I describe how to observe replication of the
      Escherichia coli chromosome in a strain that synthesizes a fluorescent derivative
      of SSB. This methodology provides information about the position and dynamics of
      DNA replication through epifluorescence.

PMID- 22976194
TI  - [Current aspects of therapy studies of acute stroke].

PMID- 22976195
TI  - Dispersant use as a response to oil spills: toxicological effects on fish cardiac
      performance.
AB  - Dispersant use is a controversial technique used to respond to oil spills in
      nearshore areas. In order to assess the toxicity of this technique, this study
      evaluated the cardiac toxicological effects on juvenile golden grey mullets Liza
      aurata exposed for 48 h to either dispersant alone, chemically dispersed oil,
      mechanically dispersed oil, the water-soluble fraction of oil or a control
      condition. Following exposure, the positive inotropic effects of adrenaline were
      assessed in order to evaluate a potential impairment on the cardiac performance.
      The results revealed an impairment of the positive inotropic effects of
      adrenaline for all the contaminants (single dispersant, dispersed and undispersed
      oil, water-soluble fraction of oil). This suggests that: (1) cardiac performance
      is a valuable parameter to study the physiopathological effects of dispersed oil;
      (2) dispersant application is likely to impair cardiac performance.

PMID- 22976196
TI  - Sperm from pheromone primed brown trout (Salmo trutta L.) produce more larvae.
AB  - Male goldfish (Carassius auratus) exposed to female hormonal pheromones express
      increased milt volumes and their sperm fertilize more eggs than sperm from
      unprimed males. Ovulated salmonid females also release odours that increase
      volumes of strippable milt in males. It is, however, not known if the priming
      pheromones affect the ability of sperm to fertilize eggs in salmonids. In this
      study, we compare the proportion of larvae produced from in vitro fertilization
      tests between primed brown trout (Salmo trutta) males exposed to a mix of female
      urine and ovarian fluids, and control males exposed only to 0.9 % sodium
      chloride. We also investigate priming effects on milt yield and sperm motility.
      Fertilization tests with sperm from single males, as well as sperm from two males
      (i.e., sperm competition), were performed. Primed males generated more larvae in
      both the single male and competition fertilization tests. No differences between
      treatments in milt yield and sperm motility could be established.

PMID- 22976197
TI  - Bispecific antibody derivatives with restricted binding functionalities that are
      activated by proteolytic processing.
AB  - We have designed bispecific antibodies that bind one target (anti-Her3) in a
      bivalent IgG-like manner and contain one additional binding entity (anti-cMet)
      composed of one V(H) and one V(L) domain connected by a disulfide bond. The
      molecules are assembled by fusing a V(H,Cys44) domain via flexible connector
      peptides to the C-terminus of one H-chain (heavy chain), and a V(L,Cys100) to
      another H-chain. To ensure heterodimerization during expression in mammalian
      cells, we introduced complementary knobs-into-holes mutations into the different
      H-chains. The IgG-shaped trivalent molecules carry as third binding entity one
      disulfide-stabilized Fv (dsFv) without a linker between V(H) and V(L). Tethering
      the V(H) and V(L) domains at the C-terminus of the C(H)3 domain decreases the on
      rates of the dsFv to target antigens without affecting off-rates. Steric
      hindrance resolves upon removal of one side of the double connection by
      proteolysis: this improves flexibility and accessibility of the dsFv and fully
      restores antigen access and affinity. This technology has multiple applications:
      (i) in cases where single-chain linkers are not desired, dsFvs without linkers
      can be generated by addition of furin site(s) in the connector that are processed
      during expression within mammalian cells; (ii) highly active (toxic) entities
      which affect expression can be produced as inactive dsFvs and subsequently be
      activated (e.g. via PreScission cleavage) during purification; (iii) entities can
      be generated which are targeted by the unrestricted binding entity and can be
      activated by proteases in target tissues. For example, Her3-binding molecules
      containing linkers with recognition sequences for matrix metalloproteases or
      urokinase, whose inactivated cMet binding site is activated by proteolytic
      processing.

PMID- 22976198
TI  - Population-based treated prevalence of congenital heart disease in a pediatric
      cohort.
AB  - Extant epidemiologic results for pediatric congenital heart disease (CHD) are
      dated. Given the degree of variability in previous prevalence estimates and the
      rapid changes in pediatric cardiology diagnostic and treatment procedures, a
      reexamination of these rates represents a potentially important update in this
      area of inquiry. This report characterizes the prevalence rates of children with
      CHD in one state's treated pediatric population by type of lesion and in
      comparison with published rates from previous studies. Two 15-year data sets
      (1996-2010) are analyzed. The inclusion criteria for the study required the
      participants to be 17 years or younger, enrollees in the South Carolina State
      Medicaid or State Health Plan, and recipients of a CHD diagnosis on one or more
      service visits to a pediatrician or pediatric cardiologist. A 15-year accrued
      prevalence rate for pediatric CHD of 16.7 per 1,000 was found among 1,145,364
      unduplicated children served. The annual incidence rates varied from 6.3 to 8.6
      per 1,000, with an initial downward trend from 1996 to 2002 followed by an upward
      trend from 2003 to 2008. A higher prevalence of atrioventricular
      canal/endocardial cushion defects, common/single ventricle, double-outlet right
      ventricle, tetralogy of Fallot, and truncus arteriosus and a lower prevalence of
      dextro-transposition of the great arteries were diagnosed in South Carolina than
      in other states and countries according to published results. The study results
      underscore the need for periodic updating of prevalence data for pediatric CHD,
      both in total and for specific lesions, to anticipate and provide more
      specialized care to young patients with CHD, especially in the more rare and
      complex cases.

PMID- 22976199
TI  - Re: Schwab F, Ungar B, Blondel B, et al. Scoliosis research society-Schwab adult
      spinal deformity classification--a validation study. Spine 2012; 37:1077-82.

PMID- 22976201
TI  - Optimal pain management after aortic valve implantation: an opportunity to
      improve outcomes after transapical access in the future?

PMID- 22976202
TI  - SIMSUG 2011, Lancaster Environment Centre, 23-24 November, 2011.

PMID- 22976203
TI  - Soil mineral N retention and N(2) O emissions following combined application of
      (15) N-labelled fertiliser and weed residues.
AB  - RATIONALE: The combination of plant residues with inorganic fertiliser-N provides
      the potential to increase N-use efficiency in agricultural fruit production
      systems, such as olive orchards. The development of weeds in the inter-canopy
      area of olive orchards is encouraged as a novel strategy to reduce soil erosion.
      However, little is known about soil N retention or N(2) O production following
      the combined application of inorganic-N with the mulched weed residues. METHODS:
      Emissions of (15) N-N(2) O and soil mineral (15) N retention were measured
      following combined applications of (15) N-labelled fertiliser and a range of
      olive crop weed residues to a silty loam soil under controlled conditions. These
      plant residues differed in their C:N ratios, lignin and polyphenol contents.
      RESULTS: The magnitude of soil (15) N-NO(3) (-) retention from combining plant
      residues and fertiliser-N was highly dependent on potential N mineralisation (r =
      -0.96) and the (lignin + polyphenol)-to-N ratio (r = 0.98) of the residues.
      Fertiliser-N-derived retention was zero for a legume-based mulch but up to 80% in
      the treatment containing plant residues with a high (lignin + polyphenol)-to-N
      ratio. N(2) O emissions increased after the addition of residues, and increased
      further (up to 128%) following the combined application of inorganic fertiliser
      and residues. Fertiliser-derived (15) N-N(2) O was <1.4% of the total (14+15) N
      N(2) O emission and <0.01% of the applied (15) N-NO(3) (-) . Enhanced N(2) O
      emissions following the application of residues and the fertiliser-N values were
      positively correlated with the C:N ratio of the residue. Thus, combining organic-
      and inorganic-N immobilised a significant proportion of the inorganic N with
      little increase in N(2) O, especially in low C:N ratio residues. CONCLUSIONS: The
      results demonstrate that whilst there is potential for N(2) O emissions to be
      controlled by combining weed residues and inorganic fertilisers, this is not easy
      to achieve as the magnitude and direction of interactions vary between different
      species due to their varying substrate qualities.

PMID- 22976204
TI  - Stable carbon isotope analysis of fluvial sediment fluxes over two contrasting
      C(4) -C(3)  semi-arid vegetation transitions.
AB  - RATIONALE: Globally, many drylands are experiencing the encroachment of woody
      vegetation into grasslands. These changes in ecosystem structure and processes
      can result in increased sediment and nutrient fluxes due to fluvial erosion. As
      these changes are often accompanied by a shift from C(4) to C(3) vegetation with
      characteristic delta(13) C values, stable isotope analysis provides a promising
      mechanism for tracing these fluxes. METHODS: Input vegetation, surface sediment
      and fluvially eroded sediment samples were collected across two contrasting C(4) 
      C(3) dryland vegetation transitions in New Mexico, USA. Isotope ratio mass
      spectrometric analyses were performed using a Carlo Erba NA2000 analyser
      interfaced to a SerCon 20-22 isotope ratio mass spectrometer to determine bulk
      delta(13) C values. RESULTS: Stable isotope analyses of contemporary input
      vegetation and surface sediments over the monitored transitions showed
      significant differences (p <0.05) in the bulk delta(13) C values of C(4)
      Bouteloua sp. (grama) grassland, C(3) Larrea tridentata (creosote) shrubland and
      C(3) Pinus edulis/Juniperus monosperma (pinon-juniper) woodland sites.
      Significantly, this distinctive delta(13) C value was maintained in the bulk
      delta(13) C values of fluvially eroded sediment from each of the sites, with no
      significant variation between surface sediment and eroded sediment values.
      CONCLUSIONS: The significant differences in bulk delta(13) C values between sites
      were dependent on vegetation input. Importantly, these values were robustly
      expressed in fluvially eroded sediments, suggesting that stable isotope analysis
      is suitable for tracing sediment fluxes. Due to the prevalent nature of these
      dryland vegetation transitions in the USA and globally, further development of
      stable isotope ratio mass spectrometry has provided a valuable tool for enhanced
      understanding of functional changes in these ecosystems.

PMID- 22976205
TI  - The privileged burial of the Pava Pieve (Siena, 8th Century AD).
AB  - RATIONALE: The 6(th) archaeological excavation campaign performed at the 'Pieve
      di Pava' (San Giovanni d'Asso, Siena, Italy) unearthed a privileged stone burial
      of a single individual (US 2378), covered by a monolithic slab and placed in
      front of an altar. The skeletal remains of a young male (18-20 years old), not in
      anatomical connection, were found at the bottom floor of a tomb (160 cm long, 40
      cm large and over 70 cm deep). METHODS: A multidisciplinary study has been
      carried out concerning that privileged bone burial. The study combines
      paleopathology studies, stable isotope palaeodietary reconstruction, radiocarbon
      dating and archaeological analyses. RESULTS: (14)  C dating of the skeleton
      revealed a date between 650 and 688 AD. Stable isotope analysis (delta(18) O,
      delta(13) C, delta(15) N) attested that he was probably a member of the local
      population, whose diet was rather rich in animal proteins. The paleopathological
      study diagnosed a case of acromesomelic dysplasia, a congenital anomaly with
      disproportion of the limbs. Archaeological evidence regarding the circular
      delimitation of the bones suggested that the skeleton was a secondary deposition,
      transported to the church in a sack. CONCLUSIONS: We argue that the relic was
      used for the re-consecration of the church, following the restoration work in the
      8(th) century. We conclude that the skeleton belonged to an eminent personage
      (e.g., either the member of a local elite family or a saint).

PMID- 22976206
TI  - Palaeoenvironmental modelling of delta(13) C and delta(15) N values in the North
      Atlantic Islands: understanding past marine resource use.
AB  - RATIONALE: Carbon (delta(13) C) and nitrogen (delta(15) N) analysis has been
      extensively used to investigate the importance of marine foods in the diet of
      archaeological populations in the North Atlantic Islands; however, few faunal
      studies exist to aid the interpretation of results. Palaeoenvironmental modelling
      of delta(13) C and delta(15) N values is crucial in determining whether changes
      in the stable isotope values are a result of dietary change, rather than temporal
      or geographical fluctuations in carbon and nitrogen. Investigating faunal dietary
      behaviour can provide an insight into past foddering and land management
      strategies. METHODS: Detailed sampling of wild and domestic species for bulk
      collagen analysis was undertaken in order to characterise geographical variations
      in delta(13) C and delta(15) N values in the Outer Hebrides and Orkney. Samples
      from the Neolithic to the Norse period were analysed to assess temporal and
      geographical variations in delta(13) C and delta(15) N values, in addition to
      determining the contribution of marine foods to the diet of local fauna. RESULTS:
      A delta(15) N shift of 10/00 was observed between the Outer Hebrides and Orkney
      in the Neolithic and Iron Age. A geographical variation in delta(13) C values was
      observed in the Norse period between Orkney and the Outer Hebrides. Temporal
      fluctuations in delta(13) C and delta(15) N values demonstrate variations in
      foddering practices of sheep in the Outer Hebrides. Pig specimens from the Outer
      Hebrides demonstrated evidence of marine food consumption in the Iron Age.
      CONCLUSIONS: Faunal dietary behaviour can act as a vital indicator of the
      importance of marine resources in the past. Characterisation of faunal delta(13)
      C and delta(15) N values geographically and temporally is crucial in our
      interpretation of human dietary behaviour.

PMID- 22976207
TI  - delta(18) O analysis of organic compounds: problems with pyrolysis in molybdenum
      lined reactors.
AB  - RATIONALE: Effective delta(18) O determinations of organic compounds have been
      made using high-temperature pyrolysis (HTP) units that employ molybdenum (Mo)
      foil as an oxidation barrier instead of glassy carbon. In this investigation we
      evaluated the performance of a Mo-lined reactor during delta(18) O determinations
      from benzoic acid using a standard high-temperature conversion elemental analyser
      (TC/EA) unit. Our Mo-lined reactor was associated with poor performance
      statistics. It was hypothesised that this was as a consequence of the
      partitioning of oxygen within our system. METHODS: In order to test this
      hypothesis scanning electron microscopy energy-dispersive X-ray spectroscopy (SEM
      EDX) and Raman spectroscopy was conducted on two Mo-lined reactors, which had
      been used for the analysis of benzoic acids. RESULTS: The EDX analysis revealed
      that the Mo metal, which had become severely pitted and corroded in the region
      corresponding to the hottest part of the furnace, was associated with Mo-oxide
      patinas throughout its entire length. CONCLUSIONS: A complex circular reaction
      between CO, Mo and C is likely to be responsible for the sequestering of a
      portion of sample oxygen into Mo-oxides, fractionating our sample. Accurate
      analysis of benzoic acid and other compounds can therefore only be achieved if
      sample oxygen is quantitatively returned to gaseous CO, preventing the buildup of
      Mo-oxides within the reactor over time. This is most likely to be achieved if
      sample gases have a sufficient residence time within the reactive glassy carbon
      bed, optimising the recovery of sample oxygen. However, such conditions are
      unlikely to have been met within our standard TC/EA system resulting in poor
      performance of the Mo-liner compared with other HTP units.

PMID- 22976208
TI  - Understanding spatial variability of soil properties: a key step in establishing
      field- to farm-scale agro-ecosystem experiments.
AB  - RATIONALE: The spatial variability of soil properties is poorly understood,
      despite its importance in designing appropriate experimental sampling strategies.
      As preparation for a farm-scale agro-ecosystem services monitoring project, the
      'North Wyke Farm Platform', there was a need to assess the spatial variability of
      key soil chemical and physical properties. METHODS: The field-scale spatial
      variability of soil chemical (total N, total C, soil organic matter), soil
      physical properties (bulk density and particle size distribution) and stable
      isotope ratios (delta(13) C and delta(15) N values) was studied using
      geostatistical approaches in an intensively managed grassland. RESULTS: The
      scales over which stable isotopes vary (ranges: 212-258 m) were larger than those
      of the total nutrients, soil organic matter and bulk density (ranges: 84-170 m).
      Two visually and statistically distinct areas of Great Field (north and south)
      were identified in terms of co-occurring high/low values of several soil
      properties. CONCLUSIONS: The resulting patterns of spatial variability suggest
      lower spatial variability of stable isotopes than that of total nutrients, soil
      organic matter and bulk density. Future sampling regimes should be conducted in a
      grid with <85 m distance between sampling locations to sufficiently capture the
      spatial variability of the measured soil properties on the 'North Wyke Farm
      Platform'. Consultation of the management histories of the sampled field revealed
      that it had previously comprised two fields with contrasting management
      histories, suggesting an effect of management legacy (>5 years) on the patterns
      of spatial variability.

PMID- 22976209
TI  - Greenhouse gas (GHG) emissions from soils amended with digestate derived from
      anaerobic treatment of food waste.
AB  - RATIONALE: The application of organic materials to agricultural lands is
      considered good practice to improve soil organic matter content and recycle
      nutrients for crop growth. The anaerobic treatment of food waste may have
      environmental benefits, particularly with regard to greenhouse gases (GHGs)
      mitigation and enhancement of carbon sequestration. METHODS: This work presents
      the results from a field experiment to evaluate CO(2) , CH(4) and N(2) O
      emissions from grassland amended with digestate produced by anaerobic
      fermentation of food waste. Experimental plots, located close to Rothamsted
      Research-North Wyke, were established using a randomized block design with three
      replicates and two treatments, added digestate (DG) and the unamended control
      (CNT). The digestate was applied on three occasions at an equivalent rate of 80
      kg N ha(-1) . RESULTS: The application of digestate led to an increase in CO(2)
      emissions, especially after the 2(nd) application (74.1 kg CO(2) -C ha(-1)  day(
      1) ) compared with the CNT soil (36.4 kg CO(2) -C ha(-1)  day(-1) ), whereas DG
      treatment did not affect the overall CH(4) and N(2) O emissions. The total grass
      yield harvested on a dry matter basis was greater in the DG treated plots (0.565
      kg m(-2) ) than in the CNT plots (0.282 kg m(-2) ), as was the (15)  N content in
      the harvest collected from the DG plots. CONCLUSIONS: The results suggest that
      the digestate can be applied to agricultural land as a fertilizer to grow crops.
      Our study was conducted in an exceptionally dry growing season, so conclusions
      about the effect of digestate on GHG emissions should take this into account, and
      further field trials conducted under more typical growing seasons are needed.

PMID- 22976210
TI  - Comparison of electrospray ionisation, atmospheric pressure chemical ionisation
      and atmospheric pressure photoionisation for the identification of metabolites
      from labile artemisinin-based anti-malarial drugs using a QTRAP(r) mass
      spectrometer.
AB  - RATIONALE: Artemisinin-based drugs and their metabolites are prone to in-source
      fragmentation under atmospheric pressure ionisation mass spectrometry (API-MS)
      conditions. To facilitate correct and efficient identification of all possible
      drug metabolites using full scan MS analyzer methods, stable [M + NH(4) ](+) ions
      should be produced in the MS source. METHODS: Using a high-performance liquid
      chromatography (HPLC) hybrid triple quadrupole linear ion trap MS system,
      electrospray ionisation (ESI), atmospheric pressure chemical ionisation (APCI)
      and atmospheric pressure photoionisation (APPI) methods were developed for the
      detection of [M + NH(4) ](+) ions of the test compounds dihydroartemisinin,
      artemisinin, artemether and artesunic acid. The optimised methods employed
      ammonium formate buffered HPLC mobile phase in combination with moderate source
      temperatures (100-200  degrees C) and showed satisfactorily reduced in-source
      fragmentation. RESULTS: With a full scan MS analyser method for the detection of
      the in vitro metabolites of the test compounds, the respective performance of the
      ESI and APCI methods was found to be comparable. ESI generally resulted in less
      in-source fragmentation. Incorrect assignment of metabolites resulted from strong
      in-source fragmentation of artemether using the APPI method. The most number of
      metabolites could be detected using ESI in combination with a selective MS
      analyser method. CONCLUSIONS: ESI and APCI full scan methods proved to be capable
      of detecting any drug metabolites present in reasonable concentrations, and are
      useful when employed in addition to selective scan methods that target low level
      expected metabolites. APPI can be a valuable alternative for detecting expected
      metabolites due to good signal-to-noise (S/N) ratio.

PMID- 22976211
TI  - Identification of multiple constituents in the traditional Chinese medicine
      formula Zhi-zi-chi decoction and rat plasma after oral administration by liquid
      chromatography coupled to quadrupole time-of-flight tandem mass spectrometry.
AB  - RATIONALE: Liquid chromatography (LC) coupled to positive electrospray ionization
      (ESI) tandem mass spectrometry (MS/MS) employing a time-of-flight tandem mass
      spectrometer was established to identify multi-components of Zhi-zi-chi
      decoction, a traditional Chinese medicine formula, and the constituents in rat
      plasma after oral administration of Zhi-zi-chi decoction. METHODS: The LC
      separation was achieved on a C(18) column. The mobile phase consisted of
      acetonitrile/0.2% formic acid with gradient program. The quadrupole time-of
      flight (Q-TOF) mass spectrometer was operated in the positive ion mode with an
      electrospray ionization source (ESI+). The capillary voltage of the ion source
      was set at 4500 V and the capillary exit was 90 V. The nebulizer pressure was
      maintained at 1.2 bar. Hexapole radio frequencies 1 and 2 were set to 200 Vpp and
      250 Vpp, respectively. RESULTS: A total 47 compounds in the Zhi-zi-chi decoction
      and 24 constituents in rat plasma after oral administration of Zhi-zi-chi
      decoction were identified. Of the 47 detected compounds in the Zhi-zi-chi
      decoction, 15 were identified by comparing the retention time and MS data with
      that of reference compounds and the rest were identified by MS analysis and
      retrieving the reference literature. Of the identified 24 compounds in rat
      plasma, 19 were the original form of the compounds absorbed from the 47 detected
      compounds, and the other five were the metabolites of the compounds existing in
      the Zhi-zi-chi decoction. CONCLUSIONS: A fast and sensitive LC/Q-TOF MS method
      has been developed and successfully utilized to screen the active ingredients of
      a Chinese medical formula, Zhi-zi-chi decoction, for the first time. The results
      indicated that the 24 compounds identified in rat plasma were the potential
      active ingredients of Zhi-zi-chi decoction, which provided helpful chemical
      information for further pharmacology and active mechanism research on Zhi-zi-chi
      decoction and other traditional Chinese medicines.

PMID- 22976212
TI  - An optimized matrix-assisted laser desorption/ionization sample preparation using
      a liquid matrix, 3-aminoquinoline/alpha-cyano-4-hydroxycinnamic acid, for
      phosphopeptides.
AB  - RATIONALE: A liquid matrix, 3-aminoquinoline (3-AQ)/alpha-cyano-4-hydroxycinnamic
      acid (CHCA), introduced by Kolli et al. in 1996 for matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS), has been reported for
      peptides and proteins, oligonucleotides, oligosaccharides, and glycopeptides.
      However, it has not been validated for phosphopeptides. METHODS: We optimized
      sample preparation using 3-AQ/CHCA for phosphopeptides. The sensitivity of six
      phosphopeptide species as isolated or in digests was systematically evaluated by
      using MALDI-quadropole ion trap (QIT)-time of flight (TOF) MS in positive and
      negative ion modes, and compared with the conventional methods using a solid
      matrix, 2,5-dihydroxybenzoic acid (2,5-DHB). RESULTS: The sensitivity of mono-
      and tetraphosphopeptides was improved 10- to 10 000-fold with the optimized
      preparation method using 3-AQ/CHCA compared with the conventional methods using
      2,5-DHB. Improvement by 3-AQ/CHCA itself was 10-fold. Adding ammonium dihydrogen
      phosphate or an analyte solvent composition was also effectively improved the
      sensitivity. Phosphopeptides in isolated form or in digests were detected at
      femto- or subfemtomole levels. CONCLUSIONS: Sensitivity of phosphopeptides was
      improved by the optimized sample preparation method using 3-AQ/CHCA compared with
      the conventional method using 2,5-DHB. The validation of 3-AQ/CHCA for
      phosphopeptides was systematically confirmed, expanding the potential of this
      matrix to phosphoproteomics.

PMID- 22976213
TI  - Substructure-based annotation of high-resolution multistage MS(n)  spectral
      trees.
AB  - RATIONALE: High-resolution multistage MS(n) data contains detailed information
      that can be used for structural elucidation of compounds observed in metabolomics
      studies. However, full exploitation of this complex data requires significant
      analysis efforts by human experts. In silico methods currently used to support
      data annotation by assigning substructures of candidate molecules are limited to
      a single level of MS fragmentation. METHODS: We present an extended substructure
      based approach which allows annotation of hierarchical spectral trees obtained
      from high-resolution multistage MS(n) experiments. The algorithm yields a
      hierarchical tree of substructures of a candidate molecule to explain the
      fragment peaks observed at consecutive levels of the multistage MS(n) spectral
      tree. A matching score is calculated that indicates how well the candidate
      structure can explain the observed hierarchical fragmentation pattern. RESULTS:
      The method is applied to MS(n) spectral trees of a set of compounds representing
      important chemical classes in metabolomics. Based on the calculated score, the
      correct molecules were successfully prioritized among extensive sets of
      candidates structures retrieved from the PubChem database. CONCLUSIONS: The
      results indicate that the inclusion of subsequent levels of fragmentation in the
      automatic annotation of MS(n) data improves the identification of the correct
      compounds. We show that, especially in the case of lower mass accuracy, this
      improvement is not only due to the inclusion of additional fragment ions in the
      analysis, but also to the specific hierarchical information present in the MS(n)
      spectral trees. This method may significantly reduce the time required by MS
      experts to analyze complex MS(n) data.

PMID- 22976214
TI  - A rapid oxygen exchange on prostaglandins in plasma represents plasma esterase
      activity that is inhibited by diethylumbelliferyl phosphate with high affinity.
AB  - RATIONALE: Fatty acids (FA) labeled with (18) O at the carboxyl group, including
      oxidized species (FA(18) O), are a useful, low-cost, and easy to prepare tool for
      quantitative and qualitative mass spectrometry (MS) analysis in biological
      systems. In addition, they are used to trace the fate of FAs in metabolic
      pathways including FA re-esterification and lipid remodeling pathways. Although a
      rapid (18) O exchange on FA(18) O in biological systems has been reported, the
      mechanism contributing to (18) O exchange has not been fully evaluated. This gap
      in knowledge limits the use of FA(18) O as a standard for MS and complicates data
      interpretation for FA metabolism in biological systems. METHODS: In the present
      study we have addressed a number of possible mechanisms for a rapid (18) O
      exchange on prostaglandin E(2) (PGE(2) ) using rat plasma as a model. High
      performance liquid chromatography coupled with electrospray ionization triple
      quadrupole MS in the multiple reaction monitoring mode was used for
      quantification. RESULTS: The major mechanism for a rapid (18) O exchange on
      PGE(2) (18) O in rat plasma is PGE(2) processing with esterases, while FA re
      esterification and non-enzymatic mechanisms do not significantly contribute to
      this phenomenon. In addition, we report a highly effective inhibition of (18) O
      exchange with diethylumbelliferyl phosphate that can be used to stabilize FA(18)
      O in biological samples. CONCLUSIONS: These data indicate the necessity to
      consider esterase activity when FA(18) O are used to study FA metabolism, and the
      importance of esterase activity inhibition when FA(18) O are used as internal
      standards for MS analysis in biological systems. In addition, the results provide
      a rational for the development of new approaches to study esterase activities and
      affinity towards modified FA.

PMID- 22976215
TI  - Direct mass spectrometric screening of antibiotics from bacterial surfaces using
      liquid extraction surface analysis.
AB  - RATIONALE: There is a need to find new antibiotic agents to fight resistant
      pathogenic bacteria. To search successfully for novel antibiotics from bacteria
      cultivated under diverse conditions, we need a fast and cost-effective screening
      method. METHODS: A combination of Liquid Extraction Surface Analysis (LESA),
      automated chip-based nanoelectrospray ionization, and high-resolution mass or
      tandem mass spectrometry using an Orbitrap XL was tested as the screening
      platform. Actinobacteria, known to produce well-recognized thiazolyl peptide
      antibiotics, were cultivated on a plate of solid medium and the antibiotics were
      extracted by organic solvent mixtures from the surface of colonies grown on the
      plate and analyzed using mass spectrometry (MS). RESULTS: LESA combined with high
      resolution MS is a powerful tool with which to extract and detect thiazolyl
      peptide antibiotics from different Actinobacteria. Known antibiotics were
      correctly detected with high mass accuracy (<4 ppm) and structurally
      characterized using tandem mass spectra. Our method is the first step toward the
      development of a novel high-throughput extraction and identification tool for
      antibiotics in particular and natural products in general. CONCLUSIONS: The
      method described in this paper is suitable for (1) screening the natural products
      produced by bacterial colonies on cultivation plates within the first 2 min
      following extraction and (2) detecting antibiotics at high mass accuracy; the
      cost is around 2 Euro per sample.

PMID- 22976216
TI  - One-year measurement of organic and elemental carbon in size-segregated
      atmospheric aerosol at a coastal and suburban site in Southeast China.
AB  - To understand the influence of the urbanization process on the air quality in the
      urban neighbourhood area, the size distribution and seasonal variations of
      elemental and organic carbon in aerosols were studied at a coastal and suburban
      site in Xiamen City, China. A total of 87 samples were obtained during the one
      year measurement campaign from June 2009 to May 2010. The results indicated that
      79.3 +/- 3.2% of the organic carbon (OC) and 88.3 +/- 1.7% of the elemental
      carbon (EC) were associated with fine particles (PM(2.5)), which consist of 32.0
      +/- 8.3% of the total carbonaceous aerosol (TCA). The concentrations of the OC
      and EC in PM(2.5) were 17.8 +/- 11.2 and 3.8 +/- 1.9 MUg m(-3), respectively, and
      high concentrations were usually observed when the wind direction was northeast
      (NE). High OC/EC ratios (average 5.1) in PM(2.5) indicated the formation of
      secondary organic carbon (SOC), which contributed 60.0% to the OC and 11.0% to
      the particulate matter. At this site, SOC had a significant negative correlation
      with the temperature (R(2) = 0.42), and a favorable meteorological condition for
      SOC formation was found in the wintertime. The OC/EC ratios increased with
      particle size, while the fractions of the carbonaceous aerosols to particulate
      matter decreased. OC, EC and SOC concentrations and OC/EC ratios followed the
      same seasonal pattern of winter > spring > autumn > summer, which mainly resulted
      from the various origins of the air masses in different seasons. This study
      indicates the requirement for mitigating the pollution of carbonaceous aerosol at
      this coastal and suburban area in Xiamen City.

PMID- 22976218
TI  - [The history of the diagnostic criteria for alcoholic liver disease and current
      status of alcoholic liver disease in Japan].

PMID- 22976219
TI  - [Alcohol and cancer in the digestive tract].

PMID- 22976217
TI  - Betaine supplementation enhances anabolic endocrine and Akt signaling in response
      to acute bouts of exercise.
AB  - Our aim was to examine the effect of betaine supplementation on selected
      circulating hormonal measures and Akt muscle signaling proteins after an acute
      exercise session. Twelve trained men (age 19.7 +/- 1.23 years) underwent 2 weeks
      of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following
      a 2-week washout period, subjects underwent supplementation with the other
      treatment (B or P). Before and after each 2-week period, subjects performed an
      acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were
      measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70
      S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH
      (mean +/- SD (Area under the curve, AUC), B: 40.72 +/- 6.14, P: 38.28 +/- 5.54, p
      = 0.060) and significantly increased IGF-1 (mean +/- SD (AUC), B: 106.19 +/-
      13.45, P: 95.10 +/- 14.23, p = 0.010), but significantly decreased cortisol (mean
      +/- SD (AUC), B: 1,079.18 +/- 110.02, P: 1,228.53 +/- 130.32, p = 0.007). There
      was no difference in insulin (AUC). B increased resting Total muscle Akt (p =
      0.003). B potentiated phosphorylation (relative to P) of Akt (Ser(473)) and p70
      S6 k (Thr(389)) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK
      (Thr(172)) decreased during both treatments (both p = 0.001). Betaine (vs.
      placebo) supplementation enhanced both the anabolic endocrine profile and the
      corresponding anabolic signaling environment, suggesting increased protein
      synthesis.

PMID- 22976220
TI  - [Alcohol and pancreatitis].

PMID- 22976221
TI  - [Metabolic syndrome and chronic alcohol consumption].

PMID- 22976222
TI  - [Life style education for the patients of alcohol related diseases].

PMID- 22976223
TI  - [Clinicopathological features of serrated lesions of the colorectum].
AB  - We reviewed 428 subjects with colorectal serrated lesions resected endoscopically
      or surgically at our institution. Colorectal serrated lesions were pathologically
      divided into 3 groups: hyperplastic polyp (HP), sessile serrated adenoma/polyp
      (SSA/P), and traditional serrated adenoma (TSA). SSA/P was detected frequently in
      the right colon and SSA/P was mainly flat-elevated. Cancers occurring in SSA/P
      were found more frequently than HP or TSA. The incidence of cancer in SSA/P was
      equivalent to that of cancer in traditional adenoma. Further studies are
      warranted to clarify clinicopathological features of serrated lesions of the
      colorectum.

PMID- 22976224
TI  - [A case of posterior gastric arteriovenous malformation causing massive
      intraperitoneal hemorrhage].
AB  - We report abdominal bleeding caused by arteriovenous malformations (AVM) of the
      posterior gastric artery. A 38-year-old man visited our hospital complaining of
      epigastralgia. Enhanced abdominal CT revealed a high density spot in a huge low
      density mass. Angiographic study showed AVM of the posterior gastric artery.
      Transcatheter arterial embolization was performed and we successfully treated the
      AVM which was accompanied by abdominal bleeding.

PMID- 22976225
TI  - [18F-fluorodeoxyglucose PET/CT and small bowel endoscopy in a patient with small
      bowel leiomyoma].
AB  - A 49-year-old man was admitted to our hospital because of recurrent
      gastrointestinal bleeding of unknown origin, after repeated negative endoscopic
      and radiographic evaluation, including colonoscopy, esophago-gastro-duodenoscopy,
      CT and angiography. His condition had not been diagnosed for the past 18 years.
      18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET/CT) showed mild
      FDG uptake by a tumor of the small bowel (SUVmax 2.83), and capsule endoscopy
      (CE) and double balloon endoscopy (DBE) revealed a well-defined smooth submucosal
      tumor in the jejunum. The patient underwent a laparotomy and small bowel
      resection. The pathologic diagnosis was a small intestinal leiomyoma. Our report
      suggests the significance of combination of CE, DBE and PET/CT in the diagnosis
      of small bowel leiomyoma.

PMID- 22976226
TI  - [Idiopathic mesenteric phlebosclerosis associated with long-term use of Chinese
      herbs: a case report].
AB  - A 59-year-old woman had been admitted to our hospital every two months for over a
      past year because of severe right abdominal pain. Colonoscopy revealed dark blue
      mucosa extending from the cecum to the transverse colon, and abdominal computed
      tomography showed wall thickening and linear calcification along the wall from
      the cecum to the transverse colon. Based on these findings, the patient was given
      a diagnosis of idiopathic mesenteric phlebosclerosis. Subsequently, we found that
      she had been a long-term user of a Chinese herbal product containing Gardeniae
      fructus for allergic rhinitis. After discontinuing the product, the patient has
      been free of abdominal pain for a year.

PMID- 22976227
TI  - [Local resection of a gangliocytic paraganglioma near the papilla of Vater].
AB  - A 69-year-old man was admitted to our hospital with epigastric discomfort. Upper
      gastrointestinal endoscopy showed a submucosal tumor near the papilla of Vater.
      Abdominal CT and MRI showed a small, well-enhanced tumor. Endoscopic tumor biopsy
      was performed before the operation, but pathologic findings showed normal
      duodenal musosa. Nevertheless, since malignancy could not be ruled out, we
      resected the tumor with the sphincter of the papilla of Vater, followed by plasty
      of the orifice for the common bile duct and main pancreatic duct. We identified 3
      parts with tumor cells; epithelioid cells, spindle cells, and ganglion-like
      cells. The tumor was diagnosed as gangliocytic paraganglioma of the duodenum.
      Treatment by resecting the tumor with the sphincter of the papilla of Vater,
      followed by the plasty of the orifice for the common bile duct and main
      pancreatic duct, was selected considering the patient's safety and to achieve
      radical cure.

PMID- 22976228
TI  - [A case of anorectal malignant melanoma appearing 1 year after endoscopic mucosal
      resection of a rectal adenocarcinoma].
AB  - We present a case of a 61-year-old woman who underwent endoscopic mucosal
      resection (EMR) for early-stage colorectal cancer. However, because the condition
      of the horizontal margin of the resected tumor was unknown, she further underwent
      local transanal excision. Lower gastrointestinal endoscopy performed 1 year later
      showed protruding lesions both on the scar tissue and in the vicinity. Biopsy
      revealed malignant melanoma. She then underwent laparoscopic abdominoperineal
      resection and colostomy. This was an extremely rare case of adenocarcinoma
      complicated by malignant melanoma after resection.

PMID- 22976229
TI  - [A case of huge intrahepatic cholangiocarcinosarcoma].
AB  - A 77-year-old woman was referred to our hospital because of right-back pain.
      Dynamic computed tomography (CT) studies showed a huge tumor in the right lobe of
      the liver. After admission, transcatheter arterial embolization (TAE) was
      immediately performed because of the risk of rupture. The tumor, however, was
      hypovascular and we judged that the procedure had no effect on preventing
      rupture. Therefore, based on a diagnosis of cystadenocarcinoma or
      cholangiocarcinoma, we conducted right trisegmentectomy and caudate lobectomy in
      July 2010. The definitive pathological diagnosis was intrahepatic
      cholangiocarcinosarcoma. The postoperative course was uneventful, and the patient
      was discharged on postoperative day (POD) 17. Afterwards, despite chemotherapy
      treatment, a local recurrence on the right diaphragm was detected 2 months
      postoperatively, and she died 4 months postoperatively. Intrahepatic
      cholangiocarcinosarcoma is very rare. We report this case with a review of some
      relevant literature.

PMID- 22976230
TI  - [Two cases of neuroendocrine carcinoma in the biliary system with long-term
      survival].
AB  - We report here two cases of neuroendocrine carcinoma which occurred in the
      biliary system. The prognosis of neuroendocrine carcinoma in the biliary system
      is generally poor. However, based on the preoperative pathological diagnosis of
      neuroendocrine carcinoma, multidisciplinary treatment consisting of preoperative
      chemotherapy, chemoradiation therapy, curative resection and adjuvant
      chemotherapy seemed to be very effective and long-term survival was obtained in
      our two cases. Therefore it is essential to diagnose preoperatively to improve
      prognosis.

PMID- 22976231
TI  - The more subjects the better in research?

PMID- 22976232
TI  - Physical activity and its relationship with perceived environment among adults
      living in a region of low socioeconomic level.
AB  - BACKGROUND: The environment has a great influence on people's lifestyles and
      their capacity to choose healthy habits. The aim of this study was to investigate
      the association between perceived environment and physical activity among adults
      living in the city of Sao Paulo, Brazil. METHODS: This was a cross-sectional
      population-based study conducted with 890 people age 18 years or over. Physical
      activity was measured through the International Physical Activity Questionnaire
      (IPAQ; long version) and perceived environment was evaluated using the
      Neighborhood Walkability Scale (NEWS) adapted. Poisson's regression was used for
      statistical analyses and prevalence ratios were calculated. The outcome variable
      was the attainment of at least 150 minutes per week of physical activities. The
      independent variables consisted of perceived environment variables and control
      variables (sex, age, schooling, time living in the home, and number of cars per
      household). RESULTS: The perceived environment variables that explained physical
      activity were: receiving invitations from friends for activities (P = .012), low
      environmental pollution scores (p trend = 0.030) and high general safety scores
      (P-trend = 0.039). CONCLUSIONS: These results suggest that physical activity
      promotion in regions like this should be envisaged as a complex phenomenon and
      investments in public safety, prevention and combating of environmental pollution
      and social support networks are needed.

PMID- 22976233
TI  - High-resolution 3T MR neurography of the brachial plexus and its branches, with
      emphasis on 3D imaging.
AB  - With advancement in 3D imaging, better fat-suppression techniques, and superior
      coil designs for MR imaging and the increasing availability and use of 3T
      magnets, the visualization of the complexity of the brachial plexus has become
      facile. The relevant imaging findings are described for normal and pathologic
      conditions of the brachial plexus. These radiologic findings are supported by
      clinical and/or EMG/surgical data, and corresponding high-resolution MR
      neurography images are illustrated. Because the brachial plexus can be affected
      by a plethora of pathologies, resulting in often serious and disabling
      complications, a better radiologic insight has great potential in aiding
      physicians in rendering superior services to patients.

PMID- 22976234
TI  - Automated determination of brain parenchymal fraction in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS.
      Reduction in brain parenchymal fraction is an accepted marker of brain atrophy.
      In this study, the approach of synthetic tissue mapping was applied, in which
      brain parenchymal fraction was automatically calculated based on absolute
      quantification of the tissue relaxation rates R1 and R2 and the proton
      attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35
      control subjects were determined by using SyMap and tested in relationship to
      clinical variables. A subset of 5 patients with MS and 5 control subjects were
      also analyzed with a manual segmentation technique as a reference.
      Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects,
      each scanned 6 consecutive times. RESULTS: Patients with MS had significantly
      lower BPF (0.852 +/- 0.0041, mean +/- SE) compared with control subjects (0.890
      +/- 0.0040). Significant linear relationships between BPF and age, disease
      duration, and Expanded Disability Status Scale scores were observed (P < .001). A
      strong correlation existed between SyMap and the reference method (r = 0.96; P <
      .001) with no significant difference in mean BPF. Coefficient of variation of
      repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and
      postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and
      reproducible method for determining BPF in MS within a clinically acceptable scan
      time and postprocessing time. Results are highly congruent with those described
      using other methods and show high agreement with the manual reference method.

PMID- 22976235
TI  - Individual classification of mild cognitive impairment subtypes by support vector
      machine analysis of white matter DTI.
AB  - BACKGROUND AND PURPOSE: MCI was recently subdivided into sd-aMCI, sd-fMCI, and md
      aMCI. The current investigation aimed to discriminate between MCI subtypes by
      using DTI. MATERIALS AND METHODS: Sixty-six prospective participants were
      included: 18 with sd-aMCI, 13 with sd-fMCI, and 35 with md-aMCI. Statistics
      included group comparisons using TBSS and individual classification using SVMs.
      RESULTS: The group-level analysis revealed a decrease in FA in md-aMCI versus sd
      aMCI in an extensive bilateral, right-dominant network, and a more pronounced
      reduction of FA in md-aMCI compared with sd-fMCI in right inferior fronto
      occipital fasciculus and inferior longitudinal fasciculus. The comparison between
      sd-fMCI and sd-aMCI, as well as the analysis of the other diffusion parameters,
      yielded no significant group differences. The individual-level SVM analysis
      provided discrimination between the MCI subtypes with accuracies around 97%. The
      major limitation is the relatively small number of cases of MCI. CONCLUSIONS: Our
      data show that, at the group level, the md-aMCI subgroup has the most pronounced
      damage in white matter integrity. Individually, SVM analysis of white matter FA
      provided highly accurate classification of MCI subtypes.

PMID- 22976236
TI  - Apolipoprotein E epsilon4 does not modulate amyloid-beta-associated
      neurodegeneration in preclinical Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Among cognitively healthy older individuals, the
      relationship among the 2 hallmark proteins of AD (Abeta and tau APOE epsilon4)
      and neurodegeneration is not well-understood. Here, we investigated the
      relationship between Abeta, p-tau, and APOE epsilon4 on longitudinal brain
      atrophy in preclinical AD. MATERIALS AND METHODS: We examined 107 cognitively
      healthy older adults who underwent longitudinal MR imaging and baseline lumbar
      puncture. Within the same linear mixed-effects model, we concurrently
      investigated main and interactive effects between the APOE epsilon4 genotype and
      CSF Abeta(1-42), CSF p-tau and CSF Abeta(1-42), and the APOE epsilon4 genotype
      and CSF p-tau on entorhinal cortex atrophy rate. We also examined the
      relationship of APOE epsilon4, CSF p-tau, and CSF Abeta(1-42) on the atrophy rate
      of other AD-vulnerable neuroanatomic regions. RESULTS: The full model with main
      and interactive effects demonstrated a significant interaction only between CSF p
      tau and CSF Abeta(1-42) on entorhinal cortex atrophy rate, indicating elevated
      atrophy with time in individuals with increased CSF p-tau and decreased CSF
      Abeta(1-42). The APOE epsilon4 genotype was significantly and specifically
      associated with CSF Abeta(1-42). However, the interaction between the APOE
      epsilon4 genotype and either CSF Abeta(1-42) or CSF p-tau on entorhinal cortex
      atrophy rate was not significant. We found similar results in other AD-vulnerable
      regions. CONCLUSIONS: On the basis of our findings and building on prior
      experimental evidence, we propose a model of the pathogenic cascade underlying
      preclinical AD in which APOE epsilon4 primarily influences the pathology of
      Alzheimer disease via Abeta-related mechanisms, and in turn, Abeta-associated
      neurodegeneration occurs only in the presence of p-tau.

PMID- 22976237
TI  - Application of a computerized language lateralization index from FMRI by a group
      of clinical neuroradiologists.
AB  - BACKGROUND AND PURPOSE: Deriving accurate language lateralization from fMRI
      studies in the clinical context can be difficult, with 10%-20% incorrect
      conclusions. Most interpretations are qualitative, performed by neuroimaging
      experts. Quantitative lateralization has been widely described but with little
      implementation in the clinical setting and is disadvantaged by the use of
      arbitrary threshold techniques. We investigated the application and utility of a
      nonthreshold CLI, in a clinical setting, as applied by a group of practicing
      neuroradiologists. MATERIALS AND METHODS: Twenty-two patients with known language
      lateralization (11 left and 11 nonleft dominant) had their images reviewed by 8
      neuroradiologists in 2 settings, all randomized, once by using a CLI and once
      without using a CLI. For each review, neuroradiologists recorded their
      impressions of lateralization for each language sequence, the overall
      lateralization conclusion, their impression of scan quality and noise, and the
      subjective confidence in their conclusion. RESULTS: The inter-rater kappa for
      lateralization was 0.64, which increased to 0.70 with the use of CLI. The group
      accuracy of overall lateralization was 78%, which increased to 81% with the use
      of a CLI. Using a CLI removed 2 instances of significant errors, with a
      neuroradiologist's impression of left lateralization in a patient with known
      right lateralization. Using a CLI had no effect on examinations with conclusions
      formed with either high confidence or no confidence. CONCLUSIONS: Although the
      overall clinical benefit of a CLI is modest, the most significant impact is to
      reduce the most harmful misclassification errors, particularly in fMRI
      examinations that are suboptimal.

PMID- 22976238
TI  - The role of the occipital artery in the diagnosis of intracranial dural
      arteriovenous fistula using duplex sonography.
AB  - BACKGROUND AND PURPOSE: The occipital artery is usually a main feeding artery of
      an intracranial dural arteriovenous fistula. The aim of this study was to
      establish the role of the OA in the diagnosis of DAVFs by using duplex
      sonography. MATERIALS AND METHODS: We first compared the clinical features
      between patients with DAVFs having and not having the OA as one of feeding
      arteries in 181 consecutive patients with DAVFs. Second, we investigated the OA
      by using duplex sonography in 60 control subjects to test the accessibility.
      Finally, we studied 24 DAVF and 60 non-DAVF patients to validate the diagnostic
      performances of duplex sonography. Hemodynamic parameters, including the
      resistance index and flow velocity, were analyzed. RESULTS: Half of the DAVFs
      (51%) had the OA as one of feeding arteries. DAVFs with the OA as one of the
      feeders were more likely located at noncavernous sinuses; to belong to types IIb,
      IIa+b, III, IV, or V; and to be associated with aggressive manifestations
      compared with DAVFs without the OA as a feeder (P < .05). Accessibility of the OA
      by using duplex sonography was 100%. The resistance index was lower and flow
      velocity was higher in the OA among patients with DAVFs compared with control
      subjects (P < .001). An OA resistance index <0.76 yielded a sensitivity and
      specificity of 96% and 97%, respectively, for the diagnosis of a DAVF.
      CONCLUSIONS: The OA resistance index can be used to screen for DAVFs having the
      OA as one of feeding arteries, and this kind of DAVF was usually associated with
      nonbenign clinical courses.

PMID- 22976239
TI  - Diffusion tensor imaging-demonstrated differences between hemiplegic and diplegic
      cerebral palsy with symmetric periventricular leukomalacia.
AB  - BACKGROUND AND PURPOSE: Patients with cerebral palsy have variable clinical
      presentations such as hemiplegic, diplegic, or quadriplegic patterns though they
      have PVL on conventional MR images. The authors investigated whether DTT can
      differentiate between hemiplegic and diplegic CP in patients presenting with
      symmetric PVL on conventional MR images. MATERIALS AND METHODS: One hundred
      thirteen consecutive pediatric patients with definite hemiplegic (59 patients; 30
      boys, 29 girls; mean age, 34.19 months; range, 24-52 months) or diplegic (54
      patients; 27 boys, 27 girls; mean age, 31.07 months; range, 24-48 months)
      symptoms and bilateral symmetric PVL on conventional brain MR imaging were
      recruited. The states of CSTs were examined by using DTT, and the asymmetries of
      right and left CSTs in the hemiplegic and diplegic groups were compared by using
      asymmetric anisotropy indexes and asymmetric mean diffusivity indexes. RESULTS:
      All patients in the hemiplegic group with asymmetric results exhibited disrupted
      integrities of more affected CSTs and sparing of less affected CSTs. However,
      diplegic patients revealed symmetric disrupted findings of the right and left
      CSTs at the upper periventricular level. Asymmetric anisotropy index and
      asymmetric mean diffusivity index values were significantly higher in the
      hemiplegic group than in the diplegic group (P < .05), and these results of DTT
      significantly corresponded with their typical clinical manifestation.
      CONCLUSIONS: DTT may be very useful for the detailed estimation of the CST state
      in patients with bilateral symmetric PVL.

PMID- 22976240
TI  - Cognitive-behavioral approaches to outpatient treatment of internet addiction in
      children and adolescents.
AB  - Excessive and potentially addictive use of the Internet among children and
      adolescents has emerged as a major concern in recent times. Internet addiction is
      often conceptualized as an impulse control disorder, with features similar to
      pathological gambling. However, there remains considerable debate about the core
      components, etiological processes, course, and maintaining factors of the
      disorder. This article presents a case study of a 16-year-old male with
      generalized pathological Internet use. Critical issues relevant to case
      conceptualization, assessment, and choice of therapy are examined. Although the
      evidence base is limited in this emerging area of clinical psychology, we provide
      a summary of empirically supported cognitive-behavioral techniques for Internet
      addiction.

PMID- 22976241
TI  - Photoinduced local heating in silica photonic crystals for fast and reversible
      switching.
AB  - Fast and reversible photonic-bandgap tunability is achieved in silica artificial
      opals by local heating. The effect is fully reversible as heat rapidly dissipates
      through the non-irradiated structure without active cooling and water is
      readsorbed. The performance is strongly enhanced by decreasing the
      photoirradiated opal volume, allowing bandgap shifts of 12 nm and response times
      of 20 ms.

PMID- 22976242
TI  - Evaluation of the performance characteristics of bilayer tablets: Part I. Impact
      of material properties and process parameters on the strength of bilayer tablets.
AB  - Bilayer tableting technology has gained popularity in recent times, as bilayer
      tablets offer several advantages over conventional tablets. There is a dearth of
      knowledge on the impact of material properties and process conditions on the
      performance of bilayer tablets. This paper takes a statistical approach to
      develop a model that will determine the effect of the material properties and
      bilayer compression process parameters on the bonding strength and mode of
      breakage of bilayer tablets. Experiments were carried out at pilot scale to
      simulate the commercial manufacturing conditions. As part of this endeavor, a
      seven-factor half-fraction factorial (2(7-1)) design was executed to study the
      effect of bilayer tablet compression process factors on the bonding strength of
      bilayer tablets. Factors studied in this work include: material properties
      (plastic and brittle), layer ratio, dwell time, layer sequence, first- and second
      layer forces, and lubricant concentration. Bilayer tablets manufactured in this
      study were tested using the axial tester, as it considers both the interfacial
      and individual layer bonding strengths. Responses of the experiments were
      analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina). A model
      was fit using all the responses to determine the significant interactions (p <
      0.05). The results of this study indicated that nature of materials played a
      critical role on the strength of bilayer compacts and also on mode of fracture.
      Bilayer tablets made with brittle materials in both the layers are strongest, and
      fracture occurred in the first layer indicating that interface is stronger than
      layers. Significant interactions were observed between the selected factors and
      these results will provide an insight into the interplay of material properties,
      process parameters, and lubricant concentration on the bonding strength and mode
      of breakage of bilayer tablets.

PMID- 22976243
TI  - Reconstruction of an extensive anterior skull base defect using a muscle-sparing
      rectus abdominis myocutaneous flap in a 1-year-old infant.
AB  - Despite the recent advances in microsurgical techniques, reconstruction of
      extensive skull base defects using free flaps in pediatric patients presents a
      surgical challenge, and reports on skull base reconstruction in infants is quite
      limited. We present a case of reconstruction of an extensive anterior skull base
      defect using a rectus abdominis (RA) myocutaneous flap in a 1 year-old (14
      months) infant. Sufficient coverage of the intracranial contents, good aesthetic
      results, and minimal growth disturbance at the donor site were achieved by the
      muscle-sparing RA flap transfer. To the best of our knowledge, this was among the
      youngest case of skull base reconstruction using a free flap. The feasibility of
      free flap transfer and flap selection in pediatric skull base reconstruction is
      discussed.

PMID- 22976247
TI  - Generation and analysis of bacteriorhodopsin mutants with the potential for
      biotechnological applications.
AB  - The properties of bacteriorhodopsin (BR) can be manipulated by genetic
      engineering. Therefore, by the methods of gene engineering, Asp85 was replaced
      individually by two other amino acids (D85V, D85S). The resulting recombinant
      proteins were assembled into soybean vesicles retinylated to form functional BR
      like nano-particles. Proton translocation was almost completely abrogated by the
      mutant D85S, while the D85V mutant was partially active in pumping protons.
      Compared with wild type, maximum absorption of the mutants, D85V and D85S, were
      563 and 609 nm, which illustrated 5 nm reductions (blue shift) and 41 nm
      increases (red shift), respectively. Since proton transport activity and
      spectroscopic activities of the mutants are different, a wide variety of membrane
      bioreactors (MBr) have been developed. Modified proteins can be utilized to
      produce unique photo/Electro-chromic materials and tools.

PMID- 22976248
TI  - Primary breast amyloidosis presenting solely as nonpalpable microcalcifications:
      a case report with review of the literature.
AB  - Primary breast amyloidosis is a rare disease and usually occurs as unilateral or
      bilateral palpable masses. Primary breast amyloidosis presenting solely as
      microcalcifications is extremely rare. The authors report a case of a 73-year-old
      woman with persistent suspicious microcalcifications without palpable mass. The
      diagnosis was established by the presence of an amorphous and eosinophilic
      material that was positive for Congo red and dichroic under polarized light.
      Paraffin immunohistochemistry revealed the presence of kappa light chains (AL
      type amyloidosis). The amyloid deposits were associated with microcalcifications.
      A complete work up was performed to exclude other localisations or associated
      pathologies and was negative. The primary breast amyloidosis is discussed and a
      review of the literature is presented.

PMID- 22976249
TI  - Hyaline globules in a nasopharyngeal carcinoma.

PMID- 22976250
TI  - The Punch and Judy show visits histopathology.

PMID- 22976251
TI  - Evolution of complex density-dependent dispersal strategies.
AB  - The question of how dispersal behavior is adaptive and how it responds to changes
      in selection pressure is more relevant than ever, as anthropogenic habitat
      alteration and climate change accelerate around the world. In metapopulation
      models where local populations are large, and thus local population size is
      measured in densities, density-dependent dispersal is expected to evolve to a
      single-threshold strategy, in which individuals stay in patches with local
      population density smaller than a threshold value and move immediately away from
      patches with local population density larger than the threshold. Fragmentation
      tends to convert continuous populations into metapopulations and also to decrease
      local population sizes. Therefore we analyze a metapopulation model, where each
      patch can support only a relatively small local population and thus experience
      demographic stochasticity. We investigated the evolution of density-dependent
      dispersal, emigration and immigration, in two scenarios: adult and natal
      dispersal. We show that density-dependent emigration can also evolve to a
      nonmonotone, "triple-threshold" strategy. This interesting phenomenon results
      from an interplay between the direct and indirect benefits of dispersal and the
      costs of dispersal. We also found that, compared to juveniles, dispersing adults
      may benefit more from density-dependent vs. density-independent dispersal
      strategies.

PMID- 22976252
TI  - Using mycophenolate mofetil in steroid-resistant nephrotic syndrome.

PMID- 22976253
TI  - How neutrophil gelatinase-associated lipocalin can be presented in plasma and
      urine.

PMID- 22976254
TI  - Is a lower dose of cyclosporine required among Iranian kidney transplant
      recipients?

PMID- 22976255
TI  - Posttransplant lymphoproliferative disorders in kidney transplant patients:
      central nervous system involvement.

PMID- 22976256
TI  - Actinobaculum schaalii as a uropathogen in immunocompromised hosts.

PMID- 22976257
TI  - An overview of recent advances in pathogenesis and diagnosis of preeclampsia.
AB  - Preeclampsia is a serious complication of pregnancy, which is the cause of 60 000
      maternal deaths annually worldwide. In addition to the well-known maternal risk
      factors such as hypertension, diabetes mellitus, antiphospholipid antibody
      syndrome, obesity, aging, and multiple pregnancies, recent studies have
      identified the role of genetic and immunological factors in the pathogenesis of
      preeclampsia. In particular, imbalance between angiogenic and anti-angiogenic
      factors, anti-angiotensin II type 1 receptor antibodies and dysregulation of
      oxygen supplies can cause preeclampsia. A group of biomarkers have been
      introduced for diagnosis of preeclampsia. Chief among them is the ratio of
      soluble fms-like tyrosine kinase-1 to placental growth factor, which can be used
      in clinical practice. Recent studies have shown high specificity and sensitivity
      of these markers for early diagnosis of preeclampsia, which is critical for
      prevention of fetal and maternal complications.

PMID- 22976258
TI  - Ibn-Sina's life and contributions to medicinal therapies of kidney calculi.
AB  - Ibn-Sina (commonly known as Avicenna) is one of the most famous and influential
      scientists in the history of medicine. The Canon of Medicine, which is his most
      celebrated book in medicine, presents a summary of all the medical knowledge of
      his time. Ibn-Sina wrote a complete section about kidney calculi in his book.
      Totally, 65 herbal, 8 animal, and 4 mineral medicines are mentioned in the Canon
      of Medicine as beneficial drugs for dissolving, expelling, and preventing kidney
      calculi. Ibn-Sina introduced very advanced drug designing based on drug delivery,
      targeting the organ, deposition in the site of action, pain control, wound
      healing, clearance after action, and supporting the organ. Using Ibn-Sina's ideas
      help scientists to choose better drugs with a historical background to reduce the
      cost of therapies and research projects.

PMID- 22976259
TI  - Mycophenolate mofetil for treatment of idiopathic nephrotic syndrome in children.
AB  - INTRODUCTION: Management of frequently relapsing steroid-responsive or steroid
      resistant idiopathic nephrotic syndrome (NS) in children has been a clinical
      challenge for pediatric nephrologists. In addition, adverse effects of long-term
      corticosteroids and cyclosporine administration emerge seeking a safe and
      effective treatment. The purpose of this study was to evaluate the safety and
      efficacy of mycophenolate mofetil (MMF) in these patients. MATERIALS AND METHODS:
      This study reviewed the outcomes of children with frequently relapsing or steroid
      resistant idiopathic NS who were treated with MMF. RESULTS: A total of 36
      patients (23 boys and 13 girls) were included. Their mean age at the time of
      diagnosis of NS was 61.94 +/- 43.9 months. Of the children, 91.6% of those who
      had frequent relapses and 8.3% of those with steroid-resistant NS responded to
      MMF significantly (P < .001), with no significant association between age and
      gender with response to MMF. The treatment was well tolerated with no significant
      complications. CONCLUSIONS: In children with frequently relapsing NS, MMF was a
      safe and useful drug for maintaining remission, while it was of low value in
      children with steroid-resistant NS.

PMID- 22976260
TI  - Effect of herbal medicine achillea millefolium on plasma nitrite and nitrate
      levels in patients with chronic kidney disease: a preliminary study.
AB  - INTRODUCTION: Increased plasma nitric oxide concentration has been supposed as
      one of the possible mechanisms of bleeding tendency in patients who suffer
      chronic kidney disease. Nitric oxide-scavenging properties have been reported
      with some Achillea species. This study was designed to find any possible effect
      of Achillea millefolium on plasma nitric oxide concentration in these patients.
      MATERIALS AND METHODS: Thirty-one chronic kidney disease patients were included
      in this randomized controlled trial, of whom16 received 1.5 g of powdered A
      millefolium flower 3 days a week for 2 months, and 15 received placebo for the
      same period. Plasma samples were collected before and after the study period to
      estimate the effect of A millefolium on plasma nitric oxide metabolites (nitrite
      and nitrate). RESULTS: Although not statistically significant, plasma nitrite and
      nitrate concentrations decreased after 2 months' administration of A millefolium
      (0.82 +/- 0.51 umol/L to 0.63 +/- 0.42 umol/L and 50.55 +/- 17.92 umol/L to 44.09
      +/- 17.49 umole/L, respectively). These concentrations were slightly increased in
      the placebo group after the study period. CONCLUSIONS: Countercurrent to the
      placebo group, plasma nitric oxide metabolites were marginally decreased after A
      millefolium administration in chronic kidney disease patients. Higher doses or
      longer duration of plant administration may make these changes more significant.

PMID- 22976261
TI  - Urine neutrophil gelatinase-associated lipocalin and kidney injury in children
      with focal segmental glomerulosclerosis.
AB  - INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is proposed as a
      marker of chronic kidney disease (CKD). This study was designed to find whether
      there is a correlation between urine NGAL and progression of kidney damage in
      children with focal segmental glomerulosclerosis (FSGS). MATERIALS AND METHODS:
      Data were collected at the initial diagnosis of FSGS and after 12 months of
      treatment based on the Mendoza protocol. Twelve children with FSGS and 15 healthy
      children were included. Urine NGAL was assessed at the initiation of the study in
      the two groups and after 1 year of receiving the treatment in the FSGS group.
      RESULTS: Urine NGAL was elevated in the FSGS group (350.0 +/- 67.2 ng/mL) as
      compared to that in the control group (9.3 +/- 3.8 ng/mL; P < .001), and there
      was a significant decline after 1 year (180.0 +/- 45.9 ng/mL) in the FSGS group
      (P < .001). There were significant inverse correlations between urine NGAL and
      estimated creatinine clearance in the FSGS patients both at diagnosis (r = 
      0.589, P = .03), and after 1 year (r = -0.76, P = .009). There was a significant
      correlation between urine NGAL and urinary protein excretion in FSGS patients at
      diagnosis (r = 0.628, P = .005). CONCLUSIONS: Urine NGAL in children with FSGS
      can be used as a marker of progression of kidney damage as expressed in its
      positive correlation with both declining in glomerular filtration rate and the
      level of proteinuria even in those with remission.

PMID- 22976262
TI  - A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in
      rats.
AB  - INTRODUCTION: The nephroprotective effect of co-administration of vitamin C and
      losartan as prophylaxis against cisplatin-induced nephrotoxicity (CIN) was
      evaluated. MATERIALS AND METHODS: Co-administration of vitamin C and losartan was
      compared with losartan (10 mg/kg), vitamin C (250 mg/kg), and placebo in 4 groups
      of rats with CIN. The prophylactic agents were injected daily for a period of 4
      days, and on day 3, a single dose (6 mg/kg) of cisplatin was administrated. The
      animals were sacrificed 7 days later for pathological examination of the kidneys.
      RESULTS: Cisplatin prevented the animals' weight gain. The serum levels of
      creatinine and blood urea nitrogen increased within the groups with CIN, but no
      significant difference was observed between the groups. The prophylaxis has no
      effect on serum osmolality, total protein, or nitrite concentrations. The kidney
      tissue damage was scored, and losartan provided a lower damage score than vitamin
      C and a combination of vitamin C and losartan. CONCLUSIONS: We concluded that co
      administration of vitamin C and losartan was not more effective than the
      administration of vitamin C or losartan alone.

PMID- 22976263
TI  - High-flux and low-flux dialysis membranes and levels of intercellular adhesion
      molecule-1 and vascular cell adhesion molecule-1 in children with chronic kidney
      failure.
AB  - INTRODUCTION: During hemodialysis, the expression of different adhesion molecules
      changes, thus serving as markers of biocompatibility of dialysis membranes. Our
      aim was to investigate whether low-flux and high-flux dialysis membranes have
      different effects on the concentration of adhesion molecules and their
      association with leukocytes and pro-inflammatory cytokines. MATERIALS AND
      METHODS: We enrolled 80 pediatric patients on hemodialysis. Baseline levels of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) were measured. The patients were classified into 2 groups to use either
      low-flux filters or high-flux filters for 3 months. At the end of the 3 months,
      predialysis samples were obtained for measurement of ICAM-1, VCAM-1, TNF-alpha
      and interleukin-1. Post-dialysis samples were collected for measurement of CBC,
      ICAM-1, VCAM-1, TNF-alpha, and interleukin-1. Forty volunteers were involved as a
      control group. RESULTS: Both TNF- ? and IL-1 were higher in the patients compared
      to the control group (P < .001). Compared to the control group, there was a
      significant increase in ICAM-1 and VCAM-1 (P < .001) in both groups predialysis
      and postdialysis. The postdialysis increments of ICAM-1 with the high-flux
      membranes were significantly less compared to the low-flux membranes (P < .001).
      Serum ICAM-1 and VCAM-1 significantly correlated with TNF-? and interleukin-1 in
      all groups. CONCLUSIONS: The postdialysis increments of the adhesion molecules
      are due to the effect of dialysis membranes, which is less with the use of high
      flux filters.

PMID- 22976264
TI  - Optimal blood concentration of cyclosporine among Iranian kidney transplant
      recipients.
AB  - INTRODUCTION: Clinical information concerning cyclosporine dose reduction in
      Iranian kidney transplant recipients is limited. There are data in Asian,
      Caucasian, and Iranian ethnic kidney transplant recipients that recommend the
      trough level (C0) and 2-hour postdose level (C2) of cyclosporine may be
      different. Our aim was to determine therapeutic levels of C0 and C2 at different
      time after transplantation among Iranian transplant patients. MATERIALS AND
      METHODS: Blood concentrations of cyclosporine were assessed in 4419 samples of
      kidney transplant recipients between 2008 and 2010. The patients were divided
      into 3 groups according to the time of laboratory studies (< 3 months, 4 to 12
      months, and > 1 year after transplantation). Both univariable and multivariable
      analyses were performed to determine the correlation between cyclosporine blood
      levels and serum creatinine. RESULTS: A total of 1270 kidney transplant patients
      with 4419 blood samples enrolled. The mean age of the donor was 28 +/- 6 years
      (range, 6 to 64 years) and 82.6% were men and 17.4% were women. In the subset of
      patients with serum creatinine values of at least 1.6 mg/dL for men and 1.4 mg/dL
      for women, we determined C0 and C2 levels between therapeutic and
      undertherapeutic creatinine ranges at 3 different time interval after
      transplantation, as follows: the first 3 months, 230 ng/mL to 240 ng/mL and 725
      ng/mL to 775 ng/mL; 4 to 12 months, 135 ng/mL to 156 ng/mL and 535 ng/mL to 612
      ng/mL; and after 1 year, 95 ng/mL to 120 ng/mL and 420 ng/mL to 479 ng/mL for C0
      and C2, respectively. CONCLUSIONS: The present study suggests that the
      cyclosporine levels for Iranian kidney transplant patients are lower compared to
      the recommended levels in western countries.

PMID- 22976265
TI  - Multifocal cranial plasmablastic lymphoma as a rare manifestation of
      posttransplant lymphoproliferative disorder.
AB  - We present an unusual case of a young woman who developed multiple cranial masses
      and unilateral facial palsy 10 years after a successful living-unrelated kidney
      transplant. She was diagnosed with diffuse large B-cell plasmablastic
      differentiated lymphoma, a rare form of posttransplant lymphoproliferative
      disorder.  She responded to 5 cycles of cyclophosphamide, doxorubicin,
      vincristine and prednisone chemotherapy with resolution of all cranial masses.
      However, her facial palsy did not resolve, and she died 6 months after diagnosis
      with pneumonia and sepsis.

PMID- 22976266
TI  - Actinobaculum schaalii pyelonephritis in a kidney allograft recipient.
AB  - We present a case of a 64-year-old man, a kidney transplant recipient with acute
      pyelonephritis and acute graft deterioration. He was diagnosed with Actinobaculum
      schaalii infection in urine cultures. He was treated with antibiotics for 3 weeks
      and recovered well. The case describes an unusual pathogenic infection in a
      kidney transplant patient.

PMID- 22976267
TI  - Cyclosporine trough level or 2-hour postdose level monitoring among kidney
      transplant recipients: Iranian practice.

PMID- 22976268
TI  - Re: risk factors profile and cardiovascular events in solid organ transplant
      recipients.

PMID- 22976269
TI  - Re: elevated serum levels of vitamin d in infants with urolithiasis.

PMID- 22976270
TI  - Re: maternal urinary tract infection as a risk factor for neonatal urinary tract
      infection.

PMID- 22976273
TI  - Neurogenesis in the adult mammalian brain: how much do we need, how much do we
      have?
AB  - The last two decades cytogenic processes (both neurogenic and gliogenic) driven
      by neural stem cells surviving within the adult mammalian brain have been
      extensively investigated. It is now well established that within at least two
      cytogenic niches, the subependymal zone of the lateral ventricles and the
      subgranular zone in the dentate gyrus, new neurons are born everyday with a
      fraction of them being finally incorporated into established neuronal networks in
      the olfactory bulb and the hippocampus, respectively. But how significant is
      adult neurogenesis in the context of the mature brain and what are the
      possibilities that these niches can contribute significantly in tissue repair
      after degenerative insults, or in the restoration of normal hippocampal function
      in the context of mental and cognitive disorders? Here, we summarise the
      available data on the normal behaviour of adult neural stem cells in the young
      and the aged brain and on their response to degeneration. Focus will be given,
      whenever possible, to numbers: how many stem cells survive in the adult brain,
      how many cells they can generate and at what ratios do they produce neurons and
      glia?

PMID- 22976274
TI  - Adult-born neurons in the olfactory bulb: integration and functional
      consequences.
AB  - The generation of new neurons is sustained throughout life in the olfactory
      system. In recent years, tremendous progress has been made toward understanding
      the proliferation, differentiation, migration, and integration of newborn neurons
      in the olfactory bulb. Here, we discuss recent findings that shed light on
      different aspects of the integration of adult-born neurons into olfactory
      circuitry and its significance for behavior.

PMID- 22976275
TI  - Network, cellular, and molecular mechanisms underlying long-term memory
      formation.
AB  - The neural network stores information through activity-dependent synaptic
      plasticity that occurs in populations of neurons. Persistent forms of synaptic
      plasticity may account for long-term memory storage, and the most salient forms
      are the changes in the structure of synapses. The theory proposes that encoding
      should use a sparse code and evidence suggests that this can be achieved through
      offline reactivation or by sparse initial recruitment of the network units. This
      idea implies that in some cases the neurons that underwent structural synaptic
      plasticity might be a subpopulation of those originally recruited; However, it is
      not yet clear whether all the neurons recruited during acquisition are the ones
      that underwent persistent forms of synaptic plasticity and responsible for memory
      retrieval. To determine which neural units underlie long-term memory storage, we
      need to characterize which are the persistent forms of synaptic plasticity
      occurring in these neural ensembles and the best hints so far are the molecular
      signals underlying structural modifications of the synapses. Structural synaptic
      plasticity can be achieved by the activity of various signal transduction
      pathways, including the NMDA-CaMKII and ACh-MAPK. These pathways converge with
      the Rho family of GTPases and the consequent ERK 1/2 activation, which regulates
      multiple cellular functions such as protein translation, protein trafficking, and
      gene transcription. The most detailed explanation may come from models that allow
      us to determine the contribution of each piece of this fascinating puzzle that is
      the neuron and the neural network.

PMID- 22976276
TI  - Deficient plasticity in the hippocampus and the spiral of addiction: focus on
      adult neurogenesis.
AB  - Addiction is a complex neuropsychiatric disorder which causes disruption at
      multiple levels, including cognitive, emotional, and behavioral domains.
      Traditional biological theories of addiction have focused on the mesolimbic
      dopamine pathway and the nucleus accumbens as anatomical substrates mediating
      addictive-like behaviors. More recently, we have begun to recognize the
      engagement and dynamic influence of a much broader circuitry which encompasses
      the frontal cortex, the amygdala, and the hippocampus. In particular,
      neurogenesis in the adult hippocampus has become a major focus of attention due
      to its ability to influence memory, motivation, and affect, all of which are
      disrupted in addiction. First, I summarize toxicological data that reveal
      strongly suppressive effects of drug exposure on adult hippocampal neurogenesis.
      Then, I discuss the impact of deficient neurogenesis on learning and memory
      function, stress responsiveness and affective behavior, as they relate to
      addiction. Finally, I examine recent behavioral observations that implicate
      neurogenesis in the adult hippocampus in the emergence and maintenance of
      addictive behavior. The evidence reviewed here suggests that deficient
      neurogenesis is associated with several components of the downward spiraling loop
      that characterizes addiction, including elevated sensitivity to drug-induced
      reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a
      negative affective state, memory impairment, and inflexible behavior.

PMID- 22976278
TI  - Relationship of the estrogen surge and multiple mates to cub paternity in the
      giant panda (Ailuropoda melanoleuca): implications for optimal timing of
      copulation or artificial insemination.
AB  - The effectiveness of ex situ breeding programs for endangered species can be
      limited by challenges in mimicking mating competitions that naturally occur among
      multiple mates in the wild. The objective of this study was to evaluate the
      impact of timed natural matings and/or artificial inseminations in the context of
      the urinary estrogen surge on cub production in the giant panda (Ailuropoda
      melanoleuca). We used a large cohort of giant pandas, including 12 females and 17
      males. DNA paternity exclusion was used to pinpoint accurately the interval
      during the estrogen surge that coincided with the ideal sperm deposition time to
      produce offspring. Of the 31 cubs (in 19 pregnancies), 22 (71.0%; 15 pregnancies)
      were produced from matings occurring on the day of or the day after the maximal
      urinary estrogen peak. Sixteen of the 19 pregnancies (84.2%) produced at least
      one offspring sired by the first male mating with the dam. There was a
      preponderance of twins (12 of 19; 63.2%), and dual paternities were discovered in
      3 of 12 twin sets (25%). These findings indicate a strong relationship between
      the excreted estrogen surge and sperm deposition to achieve pregnancy in the
      giant panda. To ensure the production of the most genetically diverse young, it
      is imperative that the most appropriate male mate first and on the day of or the
      day after the highest detected estrogen value. There is no advantage to
      increasing the number of copulations or mating partners within 1 day of the
      estrogen peak on the incidence of twinning, although this practice may increase
      the prevalence of dual paternity in cases of multiple births.

PMID- 22976277
TI  - Estrogen-induced maldevelopment of the penis involves down-regulation of myosin
      heavy chain 11 (MYH11) expression, a biomarker for smooth muscle cell
      differentiation.
AB  - Cavernous smooth muscle cells are essential components in penile erection. In
      this study, we investigated effects of estrogen exposure on biomarkers for smooth
      muscle cell differentiation in the penis. Neonatal rats received
      diethylstilbestrol (DES), with or without the estrogen receptor (ESR) antagonist
      ICI 182,780 (ICI) or the androgen receptor (AR) agonist dihydrotestosterone
      (DHT), from Postnatal Days 1 to 6. Tissues were collected at 7, 10, or 21 days of
      age. The smooth muscle cell biomarker MYH11 was studied in depth because
      microarray data showed it was significantly down-regulated, along with other
      biomarkers, in DES treatment. Quantitative real time-PCR and Western blot
      analyses showed 50%-80% reduction (P <= 0.05) in Myh11 expression in DES-treated
      rats compared to that in controls; and ICI and DHT coadministration mitigated the
      decrease. Temporally, from 7 to 21 days of age, Myh11 expression was onefold
      increased (P >= 0.05) in DES-treated rats versus threefold increased (P <= 0.001)
      in controls, implying the long-lasting inhibitory effect of DES on smooth muscle
      cell differentiation. Immunohistochemical localization of smooth muscle alpha
      actin, another biomarker for smooth muscle cell differentiation, showed fewer
      cavernous smooth muscle cells in DES-treated animals than in controls.
      Additionally, DES treatment significantly up-regulated Esr1 mRNA expression and
      suppressed the neonatal testosterone surge by 90%, which was mitigated by ICI
      coadministration but not by DHT coadministration. Collectively, results provided
      evidence that DES treatment in neonatal rats inhibited cavernous smooth muscle
      cell differentiation, as shown by down-regulation of MYH11 expression at the mRNA
      and protein levels and by reduced immunohistochemical staining of smooth muscle
      alpha actin. Both the ESR and the AR pathways probably mediate this effect.

PMID- 22976279
TI  - Nucleoli from two-cell embryos support the development of enucleolated germinal
      vesicle oocytes in the pig.
AB  - Recent research has shown that nucleoli of oocytes at the germinal vesicle (GV)
      stage (GV nucleoli) are not necessary for oocyte maturation but are essential for
      early embryonic development. Nucleoli of 2-cell embryos (2-cell nucleoli) have
      morphology similar to that of nucleoli in oocytes at the GV stage. In this study,
      we examined the ability of 2-cell nucleoli to substitute for GV nucleoli in terms
      of supporting early embryonic development by nucleolus aspiration (enucleolation)
      and transfer into metaphase II (MII) oocytes or 2-cell embryos that were derived
      from enucleolated oocytes at the GV stage in the pig. When 2-cell embryos were
      centrifuged to move the lipid droplets to one side of the blastomere, multiple
      nucleoli in the nucleus fused into a single nucleolus. The nucleoli were then
      aspirated from the 2-cell embryos by micromanipulation. The injection of 2-cell
      nucleoli to GV enucleolated oocytes at the MII stage rescued the embryos from the
      early embryonic arrest, and the resulting oocytes developed to blastocysts.
      However, the injection of 2-cell and GV nucleoli to 2-cell embryos derived from
      GV enucleolated oocytes rarely restored the development to blastocysts. These
      results indicate that 2-cell nucleoli support early embryonic development as GV
      nucleoli and that the presence of nucleoli is essential for pig embryos before
      the 2-cell stage.

PMID- 22976280
TI  - Piscine follicle-stimulating hormone triggers progestin production in gilthead
      seabream primary ovarian follicles.
AB  - Ovarian growth (vitellogenesis) in most lower vertebrates is mediated by
      estradiol-17beta (E2) secreted by the follicles in response to follicle
      stimulating hormone (Fsh), whereas oocyte maturation and ovulation are mediated
      by progestins, such as 17alpha,20beta-dihydroxypregn-4-en-3-one (17,20beta-P),
      produced in response to luteinizing hormone (Lh). In teleosts, follicular
      synthesis of 17,20beta-P at the time of maturation is due primarily to up
      regulation of the enzymes P450c17-II (Cyp17a2) and 20beta-hydroxysteroid
      dehydrogenase (Cbr1). Here, we show that follicular cells associated with primary
      growth (previtellogenic) oocytes of the gilthead seabream also express cyp17a2
      and cbr1, in addition to P450c17-I (cyp17a1) and aromatase (cyp19a1), enzymes
      required for E2 synthesis. Ovaries containing only oogonia and early primary
      ovarian follicles had a 60-fold higher concentration of 17,20beta-P than ovaries
      in the succeeding stages and had a higher expression of cbr1 and Fsh receptor
      (fshra). Stimulation of explants of primary follicles in vitro with recombinant
      piscine Fsh (rFsh), which specifically activates the seabream Fshra, promoted a
      rapid accumulation of 17,20beta-P, and synthesis was sustained by an external
      supply of 17alpha-hydroxyprogesterone. In the presence of Cbr1 inhibitors, rFsh
      mediated 17,20beta-P production was reduced, with a concomitant increase in
      testosterone and E2 synthesis. In primary explants, rFsh up-regulated cyp17a2 and
      cbr1 transcription and simultaneously down-regulated cyp17a1 and cyp19a1 steady
      state mRNA levels within 24 h. In contrast, in explants containing vitellogenic
      follicles, rFsh had no effect on cyp17a2 and cbr1 expression, but increased that
      of cyp17a1 and cyp19a1. These data suggest a functional Fshra-activated
      Cyp17a2/Cbr1 steroidogenic pathway in gilthead seabream primary ovarian follicles
      triggering the production of 17,20beta-P.

PMID- 22976281
TI  - Methylation of the glutathione-S-transferase M3 gene promoter is associated with
      oxidative stress in acute-on-chronic hepatitis B liver failure.
AB  - Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking
      as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on
      chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute
      severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is
      still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs
      superfamily and it has been demonstrated to contribute to oxidative stress
      mediated liver damage. The present study was aimed to determine the potential
      association between GSTM3 promoter methylation and oxidative stress in ACHBLF
      patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were
      included in this study. Methylation of GSTM3 promoter was determined using
      methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress
      including malondialdehyde (MDA) and GST were detected by enzyme-linked
      immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring
      system was used for predicting the severity and prognosis of liver failure.
      ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB
      patients (30% versus 6.7%, chi(2) = 5.455, P = 0.020). Plasma MDA and GST levels
      were significantly increased in ACHBLF patients compared with CHB patients.
      Meanwhile, MDA, MELD scores and mortality rate were significantly higher in
      methylated group than those in unmethylated group of ACHBLF patients.
      Furthermore, plasma MDA levels were positively correlated with MELD scores of
      ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter
      may contribute to oxidative stress-associated liver damage and correlate with the
      disease severity in ACHBLF.

PMID- 22976282
TI  - Measurement of muscle activities for evaluating physical burden and pain during
      mammography positioning.
AB  - Mammography has become widespread as a standard method for breast cancer
      screening. For women undergoing mammography, compression of the breast and
      special positioning are requested, and they cause the physical burden and pain.
      However, the reality of the physical burden and subjective pain associated with
      mammography are not fully understood. We therefore measured the muscle activity
      of subjects during positioning for mammography screening using surface
      electromyography to evaluate the physical burden and pain associated with the
      positioning. The subjects consisted of 15 women (age: 44.4 +/- 6.56 years old,
      height: 160 +/- 6.7 cm, weight: 55.08 +/- 3.94 kg, and body mass index: 21.4 +/-
      2.21). Measurements were performed in the mediolateral oblique position, a
      standard position for mammography. The target muscles were the
      sternocleidomastoid, biceps, trapezius and gastrocnemius muscles. A portable
      multi-purpose bio-amplifier was used for the measurements. Visual analogue scale
      (VAS), which is a tool for self-assessment of subjective pain, was used for pain
      measurement. The analysis of variance showed the significant difference in the
      amounts of muscle activities in all the target muscles between the relaxation
      phase before mammography positioning and the stress phase during mammography
      positioning. The sites with the increased muscle activities were consistent with
      the sites of pain measured with the VAS. These results suggest that positioning
      during mammography affects the muscle activity and that the increased muscle
      activity could be related to the pain. Understanding muscle activities during
      mammography is invaluable in making the pain reduction program for the subjects
      undergoing mammography.

PMID- 22976284
TI  - Four-dimensional velocity-encoded magnetic resonance imaging improves blood flow
      quantification in patients with complex accelerated flow.
AB  - PURPOSE: To evaluate the use of four-dimensional (4D) velocity-encoded magnetic
      resonance imaging (VEC MRI) for blood flow quantification in patients with
      semilunar valve stenosis and complex accelerated flow. MATERIALS AND METHODS:
      Peak velocities (Vmax) and stroke volumes (SV) were quantified by 2D and 4D VEC
      MRI in volunteers (n = 7) and patients with semilunar valve stenosis (n = 18).
      Measurements were performed above the aortic and pulmonary valve with both
      techniques and, additionally, at multiple predefined planes in the ascending
      aorta and in the pulmonary trunk within the 4D dataset. In patients, 4D VEC MRI
      streamline analysis identified flow patterns and regions of highest flow velocity
      (4D(max-targeted)) for further measurements and Vmax was also measured by Doppler
      echocardiography. RESULTS: In patients, 4D VEC MRI showed higher Vmax than 2D VEC
      MRI (2.7 +/- 0.6 m/s vs. 2.4 +/- 0.5 m/s, P < 0.03) and was more comparable to
      Doppler-echocardiography (2.8 +/- 0.7 m/s). 4D(max-targeted) revealed highest
      Vmax values (3.1 +/- 0.6 m/s). SV measurements showed significant differences
      between different anatomical levels in the ascending aorta in patients with
      complex accelerated flow, whereas differences in volunteers with laminar flow
      patterns were negligible (P = 0.004). CONCLUSION: 4D VEC MRI improves MRI-derived
      blood flow quantification in patients with semilunar valve stenosis and complex
      accelerated flow.

PMID- 22976285
TI  - Enhancement technology and outcomes: what professionals and researchers can learn
      from those skeptical about cochlear implants.
AB  - This text presents an overview of the bioethical debate on pediatric cochlear
      implants and pays particular attention to the analysis of the Deaf critique of
      implantation. It dismisses the idea that Deaf concerns are primarily about the
      upholding of Deaf culture and sign language. Instead it is argued that Deaf
      skepticism about child rehabilitation after cochlear surgery is well founded.
      Many Deaf people have lived experiences as subjects undergoing rehabilitation. It
      is not the cochlear technology in itself they view as problematic, but rather the
      subsequent rehabilitation process. Because they themselves have experienced what
      they describe as harmful effects which relate above all to the idea of
      normalization, they have articulated worries for the new generations of deaf
      children in need of rehabilitation following cochlear implant surgery. These
      insights have attracted little attention, but could represent relevant ethical
      questions of which both practitioners and researchers in the field of
      implantation might be aware.

PMID- 22976286
TI  - Habit formation among regular exercisers at fitness centers: an exploratory
      study.
AB  - BACKGROUND: Predictive modeling for physical activity behavior has included many
      different psychological components, including planning, motivation, personality,
      and self-efficacy. However, habit formation in exercise maintenance has not been
      well explored and lacks reliable measurement tools. The current study explores
      novel survey questions that examine behavioral components of exercise habit,
      including frequency, environmental cuing, and temporal constancy of behavior. We
      then relate these concepts to an established psychological measure of habit, the
      Self-Report Habit Inventory (SRHI). METHODS: One hundred and seventy-four
      exercisers were surveyed at 2 private fitness clubs. A single questionnaire was
      administered that included the SRHI and the novel behavioral questions developed
      from habit formation concepts. RESULTS: Habit formation was reported by many of
      the exercisers. Participants scoring higher on the SRHI also reported higher
      frequency of physical activity and a higher probability of environmental cuing.
      Exercise frequency did not correlate well with environmental cuing. CONCLUSIONS:
      Habit formation appears relevant to the physical activity patterns of many
      regular exercisers. However, wide variation in response styles was evident
      suggesting further development and exploration of the novel questionnaire is
      warranted. The ultimate goals are to include habit in predictive models of
      physical activity, and then to inform interventions to increase exercise
      adherence.

PMID- 22976287
TI  - Clonal trisomy 4 cells detected in the ossifying renal tumor of infancy: study of
      3 cases.
AB  - The ossifying renal tumor of infancy is a rare neoplasm diagnosed in the first 2
      years of life, predominantly in boys. The neoplasm is primarily characterized by
      the presence of a large ossifying component. Its most common mode of presentation
      is hematuria, and it has a uniformly benign behavior. The karyotypic makeup of
      the process has not been reported. Thus, a study was undertaken and it allowed
      demonstration of clonal trisomy 4, which was confirmed by the fluorescent in-situ
      hybridization-probing of two additional archival formalin-fixed, paraffin
      imbedded similar tumors. On the basis of the findings in these three cases, it
      seems that clonal trisomy 4 may be considered as a characteristic of the tumor,
      which makes it distinct from any other infantile renal tumor.

PMID- 22976288
TI  - Cognitive function in women with breast cancer receiving adjuvant chemotherapy
      and healthy controls.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of chemotherapy and
      psychological distress on cognitive function in patients with breast cancer
      receiving chemotherapy compared to healthy controls. METHODS: Eighteen women with
      non-metastatic breast cancer who have been exposed to chemotherapy were evaluated
      with a battery of neuropsychological and psychological tests before (time 1) and
      1 month after chemotherapy (time 2). Twenty healthy women were assessed at
      matched intervals. RESULTS: The relationship between cognitive change and mood
      change from time 1 to time 2 was compared between breast cancer patients and
      healthy controls. Independent t tests revealed no differences in change scores
      for each neuropsychological test and psychological questionnaire between the
      chemotherapy and control groups. However, in the chemotherapy group, change
      scores for verbal memory test and executive function test were significantly and
      negatively correlated with change score for Hospital Anxiety and Depression Scale
      (HADS)-D (r <= -0.498, p < 0.05). Furthermore, change scores for the verbal
      memory test and processing function test were also significantly and negatively
      correlated with change score for HADS-A (r <= -0.503, p < 0.05). The multiple
      regression model for the processing function test accounted for a significant
      amount of variance (model adjusted R (2) = 0.157, p < 0.05), where the standard
      partial regression coefficient for HADS-A change score was statistically
      significant (beta = -0.441, p < 0.01), whereas the standard partial regression
      coefficients for the group and for the HADS-D change score were -0.297 (p =
      0.071) and 0.026 (p = 0.868), respectively. CONCLUSIONS: Higher psychological
      distress was associated with poor cognitive function in patients receiving
      chemotherapy in this study.

PMID- 22976289
TI  - Two cases of diabetic mastopathy: MR imaging and pathological correlation.
AB  - Diabetic mastopathy is a rare benign condition associated with long-standing
      diabetes mellitus and presents with breast lumps. This report describes two cases
      in which diffusion-weighted images (DWI) on magnetic resonance imaging were quite
      different from each other. In case 1, there were hyperintense lesions on DWI, and
      surgically removed specimens revealed ductitis with marked lymphocytic
      infiltration. In case 2, no abnormal intensity was depicted on DWI, and biopsy
      specimens showed dense stromal fibrosis with mild perivascular lymphocytic
      infiltration that corresponded to previous reports. Although it is reported that
      diabetic mastopathy is composed of dense fibrous tissue with low cellularity that
      results in no hyperintense lesion on DWI, in cases with marked lymphocytic
      infiltration, strong hyperintensity can be seen on DWI mimicking malignant breast
      tumors. 

PMID- 22976290
TI  - A solid advancement for dye-sensitized solar cells.
AB  - Switching to solids: Solid-state dye-sensitized solar cells are achieving
      efficiencies similar to those of their counterparts with liquid electrolytes. The
      new p-type semiconductor CsSnI(3) was found to be an excellent replacement for
      the traditional I(-)/I(3)(-) redox system. The picture shows a cross section of a
      dye-sensitized solar cell based on CsSnI(3).

PMID- 22976292
TI  - G-actin regulates the shuttling and PP1 binding of the RPEL protein Phactr1 to
      control actomyosin assembly.
AB  - The Phactr family of PP1-binding proteins is implicated in human diseases
      including Parkinson's, cancer and myocardial infarction. Each Phactr protein
      contains four G-actin binding RPEL motifs, including an N-terminal motif,
      abutting a basic element, and a C-terminal triple RPEL repeat, which overlaps a
      conserved C-terminus required for interaction with PP1. RPEL motifs are also
      found in the regulatory domains of the MRTF transcriptional coactivators, where
      they control MRTF subcellular localisation and activity by sensing signal-induced
      changes in G-actin concentration. However, whether G-actin binding controls
      Phactr protein function - and its relation to signalling - has not been
      investigated. Here, we show that Rho-actin signalling induced by serum
      stimulation promotes the nuclear accumulation of Phactr1, but not other Phactr
      family members. Actin binding by the three Phactr1 C-terminal RPEL motifs is
      required for Phactr1 cytoplasmic localisation in resting cells. Phactr1 nuclear
      accumulation is importin alpha-beta dependent. G-actin and importin alpha-beta
      bind competitively to nuclear import signals associated with the N- and C
      terminal RPEL motifs. All four motifs are required for the inhibition of serum
      induced Phactr1 nuclear accumulation when G-actin is elevated. G-actin and PP1
      bind competitively to the Phactr1 C-terminal region, and Phactr1 C-terminal RPEL
      mutants that cannot bind G-actin induce aberrant actomyosin structures dependent
      on their nuclear accumulation and on PP1 binding. In CHL-1 melanoma cells,
      Phactr1 exhibits actin-regulated subcellular localisation and is required for
      stress fibre assembly, motility and invasiveness. These data support a role for
      Phactr1 in actomyosin assembly and suggest that Phactr1 G-actin sensing allows
      its coordination with F-actin availability.

PMID- 22976291
TI  - RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to
      determine the fate of EGFR.
AB  - Stimulation of epidermal growth factor receptor (EGFR) initiates RAS signaling
      simultaneously with EGFR internalization. Endocytosed EGFR is then either
      recycled or degraded. EGFR fate is determined in part by the RAS effector RIN1, a
      guanine nucleotide exchange factor (GEF) for RAB5 GTPases. EGFR degradation was
      slowed by RIN1 silencing, enhanced by RIN1 overexpression and accelerated by RIN1
      localization to the plasma membrane. RIN1 also directly activates ABL tyrosine
      kinases, which regulate actin remodeling, a function not previously connected to
      endocytosis. We report that RIN1-RAB5 signaling favors EGFR downregulation over
      EGFR recycling, whereas RIN1-ABL signaling stabilizes EGFR and inhibits
      macropinocytosis. RIN1(QM), a mutant that blocks ABL activation, caused EGF
      stimulated membrane ruffling, actin remodeling, dextran uptake and EGFR
      degradation. An ABL kinase inhibitor phenocopied these effects in cells
      overexpressing RIN1. EGFR activation also promotes RIN1 interaction with BIN1, a
      membrane bending protein. These findings suggest that RIN1 orchestrates RAB5
      activation, ABL kinase activation and BIN1 recruitment to determine EGFR fate.

PMID- 22976293
TI  - Comparative phenotypic analysis of the two major splice isoforms of
      phosphatidylinositol phosphate kinase type Igamma in vivo.
AB  - Localized production of polyphosphoinositides is critical for their signaling
      function. To examine the biological relevance of specific pools of
      phosphatidylinositol 4,5-bisphosphate we compared the consequences of genetically
      ablating all isoforms of phosphatidylinositol phosphate (PIP) kinase type Igamma
      (PIPKIgamma), encoded by the gene Pip5k1c, versus ablation of a specific splice
      isoform, PIPKIgamma_i2, with respect to three reported PIPKIgamma functions.
      Ablation of PIPKIgamma_i2 caused a neuron-specific endocytosis defect similar to
      that found in PIPKIgamma(-/-) mice, while agonist-induced calcium signaling was
      reduced in PIPKIgamma(-/-) cells, but was not affected in the absence of
      PIPKIgamma_i2. A reported contribution of PIPKIgamma to epithelial integrity was
      not evident in PIPKIgamma(-/-) mice. Given that mice lacking PIPKIgamma_i2 live a
      normal lifespan whereas PIPKIgamma(-/-) mice die shortly after birth, we propose
      that PIPKIgamma-mediated metabotropic calcium signaling may represent an
      essential function of PIPKIgamma, whereas functions specific to the PIPKIgamma_i2
      splice isoform are not essential for survival.

PMID- 22976294
TI  - Intercellular adhesion molecule-1 is a regulator of blood-testis barrier
      function.
AB  - The mechanism underlying the movement of preleptotene/leptotene spermatocytes
      across the blood-testis barrier (BTB) during spermatogenesis is not well
      understood largely owing to the fact that the BTB, unlike most other blood-tissue
      barriers, is composed of several co-existing and co-functioning junction types.
      In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a
      Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like
      domains, in addition to transmembrane and cytoplasmic domains] is a regulator of
      BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co
      localize with tight junction and basal ectoplasmic specialization proteins such
      as occludin and N-cadherin, which contribute to BTB function. More importantly,
      overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when
      monitored by transepithelial electrical resistance measurements, illustrating
      that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand,
      overexpression of a truncated form of ICAM-1 that consisted only of the five Ig
      like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an
      opposite effect when Sertoli cell barrier function was found to be perturbed in
      vitro; in this case, sICAM-1 overexpression resulted in the downregulation of
      several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402
      and c-Src/p-Src-Y530. These findings were expanded to the in vivo level when BTB
      function was found to be disrupted following sICAM-1 overexpression. These data
      illustrate the existence of a unique mechanism in the mammalian testis where ICAM
      1 can either positively or negatively regulate BTB function.

PMID- 22976295
TI  - Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated
      and controlled by TORC1 and functions as S6 kinase.
AB  - Target of rapamycin (TOR), an evolutionarily conserved serine/threonine protein
      kinase, plays pivotal roles in several important cellular processes in
      eukaryotes. In the fission yeast Schizosaccharomyces pombe, TOR complex 1
      (TORC1), which includes Tor2 as a catalytic subunit, manages the switch between
      cell proliferation and differentiation by sensing nutrient availability. However,
      little is known about the direct target of TORC1 that plays key roles in nutrient
      dependent TORC1 signaling in fission yeast. Here we report that in fission yeast,
      three AGC kinase family members, named Psk1, Sck1 and Sck2, which exhibit high
      homology with human S6K1, are phosphorylated under nutrient-rich conditions and
      are dephosphorylated by starvation conditions. Among these, Psk1 is necessary for
      phosphorylation of ribosomal protein S6. Furthermore, Psk1 phosphorylation is
      regulated by TORC1 in nutrient-dependent and rapamycin-sensitive manners in vivo.
      Three conserved regulatory motifs (the activation loop, the hydrophobic and the
      turn motifs) in Psk1 are phosphorylated and these modifications are required for
      Psk1 activity. In particular, phosphorylation of the hydrophobic motif is
      catalyzed by TORC1 in vivo and in vitro. Ksg1, a homolog of PDK1, is also
      important for Psk1 phosphorylation in the activation loop and for its activity.
      The TORC1 components Pop3, Toc1 and Tco89, are dispensable for Psk1 regulation,
      but disruption of pop3(+) causes an increase in the sensitivity of TORC1 to
      rapamycin. Taken together, these results provide convincing evidence that
      TORC1/Psk1/Rps6 constitutes a nutrient-dependent signaling pathway in fission
      yeast.

PMID- 22976296
TI  - CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFbeta
      type II receptor with implications for nephropathic cell phenotypes.
AB  - Signalling interplay between transforming growth factor-beta (TGFbeta) and CCN2
      [also called connective tissue growth factor (CTGF)] plays a crucial role in the
      progression of diabetic nephropathy and has been implicated in cellular
      differentiation. To investigate the potential role of microRNAs (miRNAs) in the
      mediation of this signalling network, we performed miRNA screening in mesangial
      cells treated with recombinant human CCN2. Analysis revealed a cohort of 22
      miRNAs differentially expressed by twofold or more, including members of the miR
      302 family. Target analysis of miRNA to 3'-untranslated regions (3'-UTRs)
      identified TGFbeta receptor II (TbetaRII) as a potential miR-302 target. In
      mesangial cells, decreased TbetaRII expression was confirmed in response to CCN2
      together with increased expression of miR-302d. TbetaRII was confirmed as an miR
      302 target, and inhibition of miR-302d was sufficient to attenuate the effect of
      CCN2 on TbetaRII. Data from the European Renal cDNA Biopsy Bank revealed
      decreased TbetaRII in diabetic patients, suggesting pathophysiological
      significance. In a mouse model of fibrosis (UUO), miR-302d was increased, with
      decreased TbetaRII expression and aberrant signalling, suggesting relevance in
      chronic fibrosis. miR-302d decreased TGFbeta-induced epithelial mesenchymal
      transition (EMT) in renal HKC8 epithelial cells and attenuated TGFbeta-induced
      mesangial production of fibronectin and thrombospondin. In summary, we
      demonstrate a new mode of regulation of TGFbeta by CCN2, and conclude that the
      miR-302 family has a role in regulating growth factor signalling pathways, with
      implications for nephropathic cell fate transitions.

PMID- 22976297
TI  - A key phosphorylation site in AC8 mediates regulation of Ca(2+)-dependent cAMP
      dynamics by an AC8-AKAP79-PKA signalling complex.
AB  - Adenylyl cyclase (AC) isoforms can participate in multimolecular signalling
      complexes incorporating A-kinase anchoring proteins (AKAPs). We recently
      identified a direct interaction between Ca(2+)-sensitive AC8 and plasma membrane
      targeted AKAP79/150 (in cultured pancreatic insulin-secreting cells and
      hippocampal neurons), which attenuated the stimulation of AC8 by Ca(2+) entry
      (Willoughby et al., 2010). Here, we reveal that AKAP79 recruits cAMP-dependent
      protein kinase (PKA) to mediate the regulatory effects of AKAP79 on AC8 activity.
      Modulation by PKA is a novel means of AC8 regulation, which may modulate or apply
      negative feedback to the stimulation of AC8 by Ca(2+) entry. We show that the
      actions of PKA are not mediated indirectly via PKA-dependent activation of
      protein phosphatase 2A (PP2A) B56delta subunits that associate with the N
      terminus of AC8. By site-directed mutagenesis we identify Ser-112 as an essential
      residue for direct PKA phosphorylation of AC8 (Ser-112 lies within the N-terminus
      of AC8, close to the site of AKAP79 association). During a series of
      experimentally imposed Ca(2+) oscillations, AKAP79-targeted PKA reduced the on
      rate of cAMP production in wild-type but not non-phosphorylatable mutants of AC8,
      which suggests that the protein-protein interaction may provide a feedback
      mechanism to dampen the downstream consequences of AC8 activation evoked by
      bursts of Ca(2+) activity. This fine-tuning of Ca(2+)-dependent cAMP dynamics by
      targeted PKA could be highly significant for cellular events that depend on the
      interplay of Ca(2+) and cAMP, such as pulsatile hormone secretion and memory
      formation.

PMID- 22976299
TI  - The Tetrahymena meiotic chromosome bouquet is organized by centromeres and
      promotes interhomolog recombination.
AB  - In order to form crossovers and to undergo reductional segregation during
      meiosis, homologous chromosomes must pair. In Tetrahymena, meiotic prophase
      nuclei elongate immensely, and, within the elongated nucleus, chromosomes are
      arranged with telomeres assembled at one pole and centromeres at the opposite
      pole. This organisation is an exaggerated form of the bouquet, a meiotic
      chromosome arrangement that is widely conserved among eukaryotes. We show that
      centromere function is crucial for the formation of Tetrahymena's stretched
      bouquet and, thereby, for homologue pairing. This finding adds to previous
      reports of the importance of centromeres in chromosome pairing in budding yeast
      and in Drosophila. Tetrahymena's bouquet is an ataxia telangiectasia- and RAD3
      related (ATR)-dependent meiotic DNA damage response that is triggered by meiotic
      DNA double-strand breaks (DSBs), suggesting that the bouquet is needed for DSB
      repair. However, in the present study we show that although homologous pairing is
      impeded in the absence of the bouquet, DSB repair takes place nevertheless.
      Moreover, recombinational DSB repair, as monitored by bromodeoxyuridine
      incorporation, takes place only after exit from the bouquet stage. Therefore, we
      conclude that the bouquet is not required for DSB repair per se, but may be
      necessary for the alignment of homologous loci in order to promote homologous
      crossovers over alternative repair pathways.

PMID- 22976298
TI  - The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to
      SUMOylated foci.
AB  - The small ubiquitin-like modifier (SUMO) ligase PIAS1 (Protein Inhibitor of
      Activated Stat-1) has been shown to play a role in cellular stress response by
      SUMOylating several proteins that are involved in DNA repair, apoptosis and
      transcription. In this paper, we show that PIAS1 regulates ultraviolet (UV)
      induced apoptosis by recruiting Death-associated protein 6 (Daxx) to PIAS1
      generated SUMO-foci. Cells that ectopically express PIAS1, but not other PIASes,
      show increased sensitivity to UV irradiation, suggesting that PIAS1 has a
      distinct function in UV-dependent apoptosis. Domain analysis of PIAS1 indicates
      that both PIAS1 SUMO-ligase activity and the specific localization of PIAS1
      through its N-terminal and C-terminal domains are essential for UV-induced cell
      death. Daxx colocalizes with PIAS1-generated SUMOylated foci, and the reduction
      of Daxx using RNAi alleviates UV-induced apoptosis in PIAS1-expressing cells.
      PIAS1-mediated recruitment of Daxx and apoptosis following UV irradiation are
      dependent upon the Daxx C-terminal SUMO-interacting motif (SIM). Overall, our
      data suggest that the pro-apoptotic protein Daxx specifically interacts with one
      or more substrates SUMOylated by PIAS1 and this interaction leads to apoptosis
      following UV irradiation.

PMID- 22976300
TI  - Cyclin G is involved in meiotic recombination repair in Drosophila melanogaster.
AB  - Cyclin G (CycG) belongs to the atypical cyclins, which have diverse cellular
      functions. The two mammalian CycG genes, CycG1 and CycG2, regulate the cell cycle
      in response to cell stress. Detailed analyses of the role of the single
      Drosophila cycG gene have been hampered by the lack of a mutant. We generated a
      null mutant in the Drosophila cycG gene that is female sterile and produces
      ventralised eggs. This phenotype is typical of the downregulation of epidermal
      growth factor receptor (EGFR) signalling during oogenesis. Ventralised eggs are
      also observed in mutants (for example, mutants of the spindle class) that are
      defective in meiotic DNA double-strand break repair. Double-strand breaks (DSBs)
      induce a meiotic checkpoint by activating Mei-41 kinase (the Drosophila ATR
      homologue), thereby indirectly causing dorsoventral patterning defects. We
      provide evidence for the role of CycG in meiotic checkpoint control. The
      increased incidence of DSBs in cycG mutant germaria may reflect inefficient DSB
      repair. Therefore, the downregulation of Mei-W68 (an endonuclease that induces
      meiotic DSBs), Mei-41, or Drosophila melanogaster Chk2 (a downstream kinase that
      initiates the meiotic checkpoint) rescues the cycG mutant eggshell phenotype. In
      vivo, CycG associates with Rad9 and BRCA2. These two proteins are components of
      the 9-1-1 complex, which is involved in sensing DSBs and in activating meiotic
      checkpoint control. Therefore, we propose that CycG has a role in an early step
      of meiotic recombination repair, thereby affecting EGFR-mediated patterning
      processes during oogenesis.

PMID- 22976301
TI  - Drosophila Cep135/Bld10 maintains proper centriole structure but is dispensable
      for cartwheel formation.
AB  - Cep135/Bld10 is a conserved centriolar protein required for the formation of the
      central cartwheel, an early intermediate in centriole assembly. Surprisingly,
      Cep135/Bld10 is not essential for centriole duplication in Drosophila, suggesting
      either that Cep135/Bld10 is not essential for cartwheel formation, or that the
      cartwheel is not essential for centriole assembly in flies. Using electron
      tomography and super-resolution microscopy we show that centrioles can form a
      cartwheel in the absence of Cep135/Bld10, but centriole width is increased and
      the cartwheel appears to disassemble over time. Using 3D structured illumination
      microscopy we show that Cep135/Bld10 is localized to a region between inner (SAS
      6, Ana2) and outer (Asl, DSpd-2 and D-PLP) centriolar components, and the
      localization of all these component is subtly perturbed in the absence of
      Cep135/Bld10, although the ninefold symmetry of the centriole is maintained.
      Thus, in flies, Cep135/Bld10 is not essential for cartwheel assembly or for
      establishing the ninefold symmetry of centrioles; rather, it appears to stabilize
      the connection between inner and outer centriole components.

PMID- 22976302
TI  - SDF and GABA interact to regulate axophilic migration of GnRH neurons.
AB  - Stromal derived growth factor (SDF-1) and gamma-aminobutyric acid (GABA) are two
      extracellular cues that regulate the rate of neuronal migration during
      development and may act synergistically. The molecular mechanisms of this
      interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons
      are essential for vertebrate reproduction. During development, these neurons
      emerge from the nasal placode and migrate through the cribriform plate into the
      brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal
      migration by accelerating and slowing migration, respectively. As such, this
      system was used to explore the mechanism by which these molecules act to produce
      coordinated cell movement during development. In the present study, GABA and SDF
      1 are shown to exert opposite effects on the speed of cell movement by activating
      depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride
      and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act
      synergistically to promote linear rather than random movement. The simultaneous
      activation of these signaling pathways, therefore, results in tight control of
      cellular speed and improved directionality along the migratory pathway of GnRH
      neurons.

PMID- 22976303
TI  - Single-cell analysis of Daxx and ATRX-dependent transcriptional repression.
AB  - Histone H3.3 is a constitutively expressed H3 variant implicated in the
      epigenetic inheritance of chromatin structures. Recently, the PML-nuclear body
      (PML-NB)/Nuclear Domain 10 (ND10) proteins, Daxx and ATRX, were found to regulate
      replication-independent histone H3.3 chromatin assembly at telomeres and
      pericentric heterochromatin. As it is not completely understood how PML-NBs/ND10s
      regulate transcription and resistance to viral infection, we have used a CMV
      promoter-regulated inducible transgene array, at which Daxx and ATRX are
      enriched, to delineate the mechanisms through which they regulate transcription.
      When integrated into HeLa cells, which express both Daxx and ATRX, the array is
      refractory to activation. However, transcription can be induced when ICP0, the
      HSV-1 E3 ubiquitin ligase required to reverse latency, is expressed. As ATRX and
      Daxx are depleted from the activated array in ICP0-expressing HeLa cells, this
      suggests that they are required to maintain a repressed chromatin environment. As
      histone H3.3 is strongly recruited to the ICP0-activated array but does not co
      localize with the DNA, this also suggests that chromatin assembly is blocked
      during activation. The conclusion that the Daxx and ATRX pathway is required for
      transcriptional repression and chromatin assembly at this site is further
      supported by the finding that an array integrated into the ATRX-negative U2OS
      cell line can be robustly activated and that histone H3.3 is similarly recruited
      and unincorporated into the chromatin. Therefore, this study has important
      implications for understanding gene silencing, viral latency and PML-NB/ND10
      function.

PMID- 22976305
TI  - Molecular mechanisms regulating the establishment of hepatocyte polarity during
      human hepatic progenitor cell differentiation into a functional hepatocyte-like
      phenotype.
AB  - The correct functioning of hepatocytes requires the establishment and maintenance
      of hepatocyte polarity. However, the mechanisms regulating the generation of
      hepatocyte polarity are not completely understood. The differentiation of human
      fetal hepatic progenitor cells (hFHPCs) into functional hepatocytes provides a
      powerful in vitro model system for studying the molecular mechanisms governing
      hepatocyte development. In this study, we used a two-stage differentiation
      protocol to generate functional polarized hepatocyte-like cells (HLCs) from
      hFHPCs. Global gene expression profiling was performed on triplicate samples of
      hFHPCs, immature-HLCs and mature-HLCs. When the differential gene expression was
      compared based on the differentiation stage, a number of genes were identified
      that might be essential for establishing and maintaining hepatocyte polarity.
      These genes include those that encode actin filament-binding protein, protein
      tyrosine kinase activity molecules, and components of signaling pathways, such as
      PTK7, PARD3, PRKCI and CDC42. Based on known and predicted protein-protein
      interactions, the candidate genes were assigned to networks and clustered into
      functional categories. The expression of several of these genes was confirmed
      using real-time RT-PCR. By inactivating genes using small interfering RNA, we
      demonstrated that PTK7 and PARD3 promote hepatic polarity formation and affect F
      actin organization. These results provide unique insight into the complex process
      of polarization during hepatocyte differentiation, indicating key genes and
      signaling molecules governing hepatocyte differentiation.

PMID- 22976304
TI  - Macrophages require Skap2 and Sirpalpha for integrin-stimulated cytoskeletal
      rearrangement.
AB  - Macrophages migrate to sites of insult during normal inflammatory responses.
      Integrins guide such migration, but the transmission of signals from integrins
      into the requisite cytoskeletal changes is poorly understood. We have discovered
      that the hematopoietic adaptor protein Skap2 is necessary for macrophage
      migration, chemotaxis, global actin reorganization and local actin reorganization
      upon integrin engagement. Binding of phosphatidylinositol [3,4,5]-triphosphate to
      the Skap2 pleckstrin-homology (PH) domain, which relieves its conformational auto
      inhibition, is critical for this integrin-driven cytoskeletal response. Skap2
      enables integrin-induced tyrosyl phosphorylation of Src-family kinases (SFKs),
      Adap, and Sirpalpha, establishing their roles as signaling partners in this
      process. Furthermore, macrophages lacking functional Sirpalpha unexpectedly have
      impaired local integrin-induced responses identical to those of Skap2(-/-)
      macrophages, and Skap2 requires Sirpalpha for its recruitment to engaged
      integrins and for coordinating downstream actin rearrangement. By revealing the
      positive-regulatory role of Sirpalpha in a Skap2-mediated mechanism connecting
      integrin engagement with cytoskeletal rearrangement, these data demonstrate that
      Sirpalpha is not exclusively immunoinhibitory, and illuminate previously
      unexplained observations implicating Skap2 and Sirpalpha in mouse models of
      inflammatory disease.

PMID- 22976306
TI  - Transcriptional regulation of Profilin during wound closure in Drosophila larvae.
AB  - Injury is an inevitable part of life, making wound healing essential for
      survival. In postembryonic skin, wound closure requires that epidermal cells
      recognize the presence of a gap and change their behavior to migrate across it.
      In Drosophila larvae, wound closure requires two signaling pathways [the Jun N
      terminal kinase (JNK) pathway and the Pvr receptor tyrosine kinase signaling
      pathway] and regulation of the actin cytoskeleton. In this and other systems, it
      remains unclear how the signaling pathways that initiate wound closure connect to
      the actin regulators that help execute wound-induced cell migrations. Here, we
      show that chickadee, which encodes the Drosophila Profilin, a protein important
      for actin filament recycling and cell migration during development, is required
      for the physiological process of larval epidermal wound closure. After injury,
      chickadee is transcriptionally upregulated in cells proximal to the wound. We
      found that JNK, but not Pvr, mediates the increase in chic transcription through
      the Jun and Fos transcription factors. Finally, we show that chic-deficient
      larvae fail to form a robust actin cable along the wound edge and also fail to
      form normal filopodial and lamellipodial extensions into the wound gap. Our
      results thus connect a factor that regulates actin monomer recycling to the JNK
      signaling pathway during wound closure. They also reveal a physiological function
      for an important developmental regulator of actin and begin to tease out the
      logic of how the wound repair response is organized.

PMID- 22976309
TI  - Upper transversal hepatectomy.
AB  - BACKGROUND: For tumors involving hepatic veins (HV) at hepato-caval confluence
      (HC), major hepatectomy or vascular reconstruction, are recommended. Detection of
      communicating veins (CV) between adjacent HVs allows conservative hepatectomies.
      METHODS: A 61 year-old man was operated for multiple colorectal liver metastases
      (CLM). The 2 main CLM (14 and 3.5 cm in size) were adjacent, separated by the
      middle HV (MHV) at HC, and involved segments 1(paracaval portion), 7, and 8, and
      segments 4-superior(S4sup) and 1(paracaval portion), respectively. At HC the
      larger CLM invaded the right HV (RHV), and the smaller was in contact with the
      left HV (LHV). A thick inferior RHV (IRHV), and 2 CVs connecting IRHV-MHV and MHV
      LHV, were evident. RESULTS: After J-shaped thoracophrenolaparotomy,
      intraoperative ultrasound (IOUS) confirmed the CVs. Liver was detached from the
      inferior vena cava preserving the IRHV: RHV was divided, and common trunk of MHV
      LHV was taped, and, once clamped, hepato-petal flow in S4inf, S5, and S6 portal
      branches was confirmed at IOUS. Upper-transverse IOUS-guided resection,
      comprehensive of S7, S8, S4sup, and S1 (paracaval portion) with preservation of
      the CVs was performed. MHV at HC was divided once detachment of the LHV from the
      tumor was ultimate. No congestive areas remained. No postoperative mortality and
      major morbidity occurred: patient was discharge on 17th postoperative day, and is
      disease-free at 7 months after surgery. CONCLUSIONS: Detection of CVs between
      adjacent HVs enables new conservative hepatectomies for tumors at HC. The herein
      described upper transversal hepatectomy despite two HVs are resected, allows
      adequate liver outflow and remaining functional liver parenchyma.

PMID- 22976307
TI  - Apical targeting and endocytosis of the sialomucin endolyn are essential for
      establishment of zebrafish pronephric kidney function.
AB  - Kidney function requires the appropriate distribution of membrane proteins
      between the apical and basolateral surfaces along the kidney tubule. Further, the
      absolute amount of a protein at the cell surface versus intracellular
      compartments must be attuned to specific physiological needs. Endolyn (CD164) is
      a transmembrane protein that is expressed at the brush border and in apical
      endosomes of the proximal convoluted tubule and in lysosomes of more distal
      segments of the kidney. Endolyn has been shown to regulate CXCR4 signaling in
      hematopoietic precursor cells and myoblasts; however, little is known about
      endolyn function in the adult or developing kidney. Here we identify endolyn as a
      gene important for zebrafish pronephric kidney function. Zebrafish endolyn lacks
      the N-terminal mucin-like domain of the mammalian protein, but is otherwise
      highly conserved. Using in situ hybridization we show that endolyn is expressed
      early during development in zebrafish brain, eye, gut and pronephric kidney.
      Embryos injected with a translation-inhibiting morpholino oligonucleotide
      targeted against endolyn developed pericardial edema, hydrocephaly and body
      curvature. The pronephric kidney appeared normal morphologically, but clearance
      of fluorescent dextran injected into the common cardinal vein was delayed,
      consistent with a defect in the regulation of water balance in morphant embryos.
      Heterologous expression of rat endolyn rescued the morphant phenotypes.
      Interestingly, rescue experiments using mutant rat endolyn constructs revealed
      that both apical sorting and endocytic/lysosomal targeting motifs are required
      for normal pronephric kidney function. This suggests that both polarized
      targeting and postendocytic trafficking of endolyn are essential for the
      protein's proper function in mammalian kidney.

PMID- 22976310
TI  - Comments to the term "cold-induced vasodilatation" in "laser doppler perfusion
      imaging of skin territory to reflect autonomic functional recovery following
      sciatic nerve autografting repair in rats".

PMID- 22976311
TI  - Solvent-catalyzed ring-chain-ring tautomerization in axially chiral compounds.
AB  - The mechanism of ring-chain-ring tautomerization and the prominent effect of the
      solvent environment have been computationally investigated in an effort to
      explain the enantiomeric interconversion observed in 2-oxazolidinone derivatives,
      heterocyclic analogues of biphenyl atropisomers, which were isolated as single
      stable enantiomers and have the potential to be used as axially chiral catalysts.
      This study has shed light on the identity of the intermediate species involved in
      the ring-chain-ring tautomerization process as well as the catalytic effect of
      polar protic solvents. These mechanistic details will prove very useful in
      predicting and understanding ring-chain tautomeric equilibria in similar
      heterocyclic systems and will further enable experimentalists to devise
      appropriate experimental conditions in which axially chiral catalysts remain
      stable as single enantiomers.

PMID- 22976308
TI  - Fibronectin and stem cell differentiation - lessons from chondrogenesis.
AB  - The extracellular matrix (ECM) is an intricate network of proteins that surrounds
      cells and has a central role in establishing an environment that is conducive to
      tissue-specific cell functions. In the case of stem cells, this environment is
      the stem cell niche, where ECM signals participate in cell fate decisions. In
      this Commentary, we describe how changes in ECM composition and mechanical
      properties can affect cell shape and stem cell differentiation. Using
      chondrogenic differentiation as a model, we examine the changes in the ECM that
      occur before and during mesenchymal stem cell differentiation. In particular, we
      focus on the main ECM protein fibronectin, its temporal expression pattern during
      chondrogenic differentiation, its potential effects on functions of
      differentiating chondrocytes, and how its interactions with other ECM components
      might affect cartilage development. Finally, we discuss data that support the
      possibility that the fibronectin matrix has an instructive role in directing
      cells through the condensation, proliferation and/or differentiation stages of
      cartilage formation.

PMID- 22976312
TI  - Retraction note: Dual-time point positron emission tomography findings of benign
      mediastinal lymph nodes in a tuberculosis-endemic region. Jpn J Radiol (2011)
      29:682-7.

PMID- 22976313
TI  - Hepatogenous diabetes in cirrhosis: academic sport or a neglected disease?

PMID- 22976314
TI  - Differential expression of somatostatin receptor subtype 1-5 proteins in numerous
      human normal tissues.
AB  - 5 Human somatostatin receptor subtypes (sst1-5) mediate the antisecretory and
      antiproliferative effects of somatostatin. We examined somatostatin receptor
      protein expression in 28 human normal tissues. Immunostaining was performed with
      specific polyclonal antibodies for sst1-5. Staining pattern and distribution of
      ssts were evaluated. Anterior pituitary was positively stained for all 5 ssts.
      Pancreatic islets exhibited a positive staining for sst1-3 and sst5. Adrenal
      cortex expressed all 5 receptor subtypes, while the medulla was positive for sst3
      and sst5 only. The thyroid expressed sst5 only, limited to single interfollicular
      cells. All 5 ssts were detected in the ovary, limited to luteinized granulosa
      cells of the corpus luteum. In the testis, sst2A was detected in the basal parts
      of the tubules, while sst5 was positively stained in the luminal parts. Sst1 was
      found in Leydig cells only. Stomach was positively stained for all 5 ssts.
      Investigation of the kidney revealed differential expression, with sst2A being
      found in the glomerules. The tubules expressed all 5 ssts. In the bone marrow
      cells of the granulocytopoiesis expressed sst2A only. The cerebellum expressed
      sst5 in a certain cell type, representing presumably Purkinje cells, while sst2A
      was stained in intercellular fibers. The expression of somatostatin receptor
      subtypes in a variety of human normal tissues may indicate a physiological role
      in these organs. Somatostatin analogues may offer new diagnostic and therapeutic
      implications for tumours related to these tissues. However, treatment of defined
      tumours with somatostatin analogues may also alter other normal tissues.

PMID- 22976315
TI  - Synthesis and pharmacological profile of a new selective G protein-coupled
      receptor 119 agonist; 6-((2-fluoro-3-(1-(3-isopropyl-1,2,4-oxadiazol-5
      yl)piperidin-4-yl)propyl)amino)-2,3-dihydro-1H-inden-1-one.
AB  - 6-((2-Fluoro-3-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)propyl)amino)
      2,3-dihydro-1H-inden-1-one is a potent drug-like G protein-coupled receptor 119
      (GPR119) agonist. It is hoped that this compound would be instrumental in probing
      the pharmacological potential of GPR119 agonists.

PMID- 22976316
TI  - Pharmacological and pharmacokinetic studies of anti-diabetic tropolonato-Zn(II)
      complexes with Zn(S(2)O(2)) coordination mode.
AB  - Zn(II) complexes are expected to be useful in the treatment of diabetes mellitus
      because of the hypoglycemic effect produced by its insulin-mimetic activity.
      Previous reports indicated that Zn(II) complexes with coordinating sulfur exhibit
      higher insulin-mimetic activity. In this study, we investigated the
      pharmacological and pharmacokinetic differences between Zn(O(4)) and Zn(S(2)O(2))
      coordination modes of tropolonato-Zn(II) complexes with insulin-mimetic activity.
      Among the tropolonato-Zn(II) complexes with various coordination modes, di(2
      mercaptotropolonato)zinc(II) (ZT2) with the Zn(S(2)O(2)) coordination mode was
      found to exhibit the highest in vitro insulin-mimetic activity with respect to
      inhibition of free fatty acid (FFA) release and enhancement of glucose uptake in
      isolated rat adipocytes treated with adrenaline. On comparing investigations of
      the antidiabetic effect in vivo, ZT2 was found to exhibit potent hypoglycemic
      activity and improve insulin resistance in type 2 diabetic KKA(y) mice at a low
      orally administered daily dose. Di(tropolonato)zinc(II) (ZT1), which has the
      Zn(O(4)) coordination mode, had a lesser effect at the same dose. In a
      pharmacokinetic analysis based on the (65)Zn tracer method, ZT2 was found to be
      absorbed at a significantly slower rate with a longer half-life than was ZT1.
      These results suggest that the potent hypoglycemic activity of ZT2 might be
      attributed to its long half-life.

PMID- 22976317
TI  - Alterations in the detergent-induced membrane permeability and solubilization of
      saturated phosphatidylcholine/cholesterol liposomes: effects of poly(ethylene
      glycol)-conjugated lipid.
AB  - We have investigated the effects of two bile salts, chenodeoxycholate (CDC) and
      ursodeoxycholate (UDC), and a widely used detergent, Triton X-100 (T(X-100)), on
      normal and poly(ethylene glycol)-modified liposomes (PEGylated liposomes). We
      tested various lipid compositions, including hydrogenated soybean
      phosphatidylcholine/cholesterol/PEG-conjugated lipid (HSPC/PEG-lipid).
      Alterations in permeability were determined by the rate of drug release from the
      liposomes and solubilization was assessed by measuring the particle size of
      liposomes. In addition, we attempted to observe interactions between the
      detergents and lipid bilayers by using surface plasmon resonance (SPR). CDC
      induced drug release from liposomes in a dose-dependent manner, and the PEGylated
      liposomes tended to be susceptible to CDC. While UDC did not strongly induce drug
      release from liposomes, UDC exhibited a similar tendency with CDC. In case of T(X
      100), there were significant differences in the percentage of released drug
      between normal and PEGylated liposomes, and the percentage of T(X-100)-induced
      drug release further increased with an increased ratio of PEG-lipid. SPR analysis
      revealed that the lipid bilayer including PEG-lipid was selectively solubilized
      by T(X-100), correlating with the drug release data. These results suggest that
      the effect of detergents on the lipid bilayer of liposomes depends on both the
      kind of detergent and the lipid composition, including the presence or absence of
      PEG-lipid. Moreover, the effects of T(X-100) on the lipid bilayers of the
      PEGylated liposomes significantly differed from those on the lipid bilayers of
      the normal liposomes.

PMID- 22976318
TI  - Isolation of six new flavonoids from Melicope triphylla.
AB  - Six new flavonoids--5-hydroxy-3,8-dimethoxy-3',4':6,7-bismethylenedioxyflavone
      (1), 3,3',4',5-tetramethoxy-7-(3-methylbut-2-enyloxy)flavone (2), 7-(2-hydroxy-3
      methylbut-3-enyloxy)-3,3',4',5-tetramethoxyflavone (3), 7-(2-hydroxy-3-methylbut
      3-enyloxy)-3,5-dimethoxy-3',4'-methylenedioxyflavone (4), 7-(2-hydroxy-3
      methylbut-3-enyloxy)-3,3',4',5,8-pentamethoxyflavone (5), and 7-(2-hydroxy-3
      methylbut-3-enyloxy)-3,5,8-trimethoxy-3',4'-methylenedioxyflavone (6)--were
      isolated from the leaves of Melicope triphylla. In addition, six already known
      flavonoids were also detected: 5-hydroxy-3,6,7-trimethoxy-3',4'
      methylenedioxyflavone (7), 5,7-dihydroxy-3,3',4',8-tetramethoxyflavone (8), 4',5
      dihydroxy-3,3',7,8-tetramethoxyflavone (9), 3,5,6,7,8-pentamethoxy-3',4'
      methylenedioxyflavone (10), 3,5,6,7-tetramethoxy-3',4'-methylenedioxyflavone
      (11), and 3,3',4',5,6,7,8-heptamethoxyflavone (12). The structures of the new
      compounds were established by spectroscopic methods. Compound 2 displayed
      ichthyotoxic activity against Japanese killifish (medaka in Japanese) (Oryzias
      latipes var.) at 10 ppm.

PMID- 22976319
TI  - Antimicrobial activity of curcumin-loaded myristic acid microemulsions against
      Staphylococcus epidermidis.
AB  - The bactericidal properties of myristic acid and curcumin were revealed in a
      number of studies. However, whether curcumin-loaded myristic acid microemulsions
      can be used to inhibit Staphylococcus epidermidis, which causes nosocomial
      infections, has not been reported. Our aim was to develop curcumin-loaded
      myristic acid microemulsions to inhibit S. epidermidis on the skin. The
      interfacial tension, size distribution, and viscosity data of the microemulsions
      were characterized to elucidate the physicochemical properties of the curcumin
      microemulsions. Curcumin distribution in neonate pig skin was visualized using
      confocal laser scanning microscopy. Dermal curcumin accumulation (326 ug/g skin)
      and transdermal curcumin penetration (87 ug/cm(2)/d) were obtained with the
      microemulsions developed herein. Curcumin at the concentration of 0.86 ug/mL in
      the myristic acid microemulsion could inhibit 50% of the bacterial growth, which
      was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO).
      The cocktail combination of myristic acid and curcumin in the microemulsion
      carrier synergistically inhibited the growth of S. epidermidis. The results we
      obtained highlight the potential of using curcumin-loaded microemulsions as an
      alternative treatment for S. epidermidis-associated diseases and acne vulgaris.

PMID- 22976320
TI  - Lignans and triterpenes from the root of Pseuderanthemum carruthersii var.
      atropurpureum.
AB  - Two new lignans, pseuderesinol (1), pseuderanoside (2) and a new triterpene,
      pseuderanic acid (3) were isolated from the dried root of Pseuderanthemum
      carruthersii (SEEM.) GUILL. var. atropurpureum (BULL.) FOSB. (Acanthaceae),
      together with ten known compounds, including five lignans, (+)-eudesmin (4), (+)
      magnolin (5), (+)-syringaresinol (6), (+)-episyringaresinol (7), (+)-1
      hydroxysyringaresinol (8) and five triterpenes, squalene (9), oleanolic acid
      (10), lupeol (11), betulin (12), betulinic acid (13). Their chemical structures
      were elucidated by 1D- and 2D-NMR, computational quantum chemistry, as well as
      high resolution-electrospray ionization (HR-ESI)-MS spectroscopic analysis. The
      acetylcholinesterase inhibition and cytotoxic activities against HeLa and MCF-7
      cancer cell lines were evaluated on some purified compounds at the concentration
      of 100 ug/mL. Pseuderesinol (1) and magnolin (5) exhibited moderate cytotoxic
      activities against the MCF-7 cancer cell line.

PMID- 22976321
TI  - Polycationic gramicidin S analogues with both high antibiotic activity and very
      low hemolytic activity.
AB  - The substitution of each constituent amino acid residue of gramicidin S (GS),
      cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue
      indicated that each side chain structure of the constituent amino acid residues
      affect largely the antibiotic activity and hemolytic activity of GS. Further, the
      substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues
      as a Lys residue results the high antibiotic activity and the very low hemolytic
      activity. Thus, we have found novel positions on the scaffold of GS at D
      Phe(4,4') and Pro(5,5') residues whose modification will significantly increase
      the therapeutic index.

PMID- 22976322
TI  - Bioconversion of 7-hydroxyflavanone: isolation, characterization and bioactivity
      evaluation of twenty-one phase I and phase II microbial metabolites.
AB  - Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella
      blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'
      dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate
      (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also
      transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate
      (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8
      dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7
      hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and
      8, flavanone 7-O-beta-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7
      O-beta-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195)
      also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor
      ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'
      trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7
      O-alpha-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19).
      The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3,
      16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A
      metabolite of 1, flavanone 7-O-beta-D-O-glucopyranoside (22) was produced by
      Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were
      elucidated by means of spectroscopic data. None of the metabolites tested showed
      antibacterial, antifungal and antimalarial activities against selected organisms.
      Metabolites 4 and 16 showed weak antileishmanial activity.

PMID- 22976323
TI  - A novel monomethoxy polyethylene glycol-polylactic acid polymeric micelles with
      higher loading capacity for docetaxel and well-reconstitution characteristics and
      its anti-metastasis study.
AB  - Docetaxel (DTX) is hydrophobic, and its available formulations (Taxotere((r)) &
      Duopafei((r))) require Tween80 and ethanol vehicle to allow parental
      administration. DTX-loaded poly(D,L-lactide)-b-polyethylene glycol-methoxy (mPEG
      b-PDLLA) polymeric micelle (PM) is a Tween80-free formulation of DTX, which has
      been extensively studied but rarely involved with industrialization issues. In
      this work, novel DTX-PM with improved loading capacity and well-reconsitution
      ability was developed. The freeze-dried DTX-PM was analyzed by HPLC, transmission
      electron microscopy (TEM) and dynamic light scattering (DLS) to determine the DTX
      loading, micelle morphology and size respectively. The in vitro cytotoxic
      activity of DTX-PM in 4T1 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and the corresponding in vivo study was
      assessed in BALB/c mice bearing 4T1 tumor through intravenous administration. The
      DTX-loading and efficiency into the micelles were 20.74+/-1.23% and 93.7+/-1.03%
      respectively, which was much higher than ever reported PM. The DTX-PM was
      spherical with a mean particle size of 16.62+/-0.31 nm, which suggested that they
      were able to selectively accumulate in solid tumors by enhanced permeability and
      retention (EPR) effect. Another important characteristic of DTX-PM is the long
      term storage and reuses as aqueous injection solution. Many kinds of
      lyoprotectants were also investigated and dextrose was found to an excellent one.
      Compared with Duopafei((r)), DTX-PM showed better cytotoxicity and anti
      metastasis ability against 4T1 cells in vitro and in vivo. In conclusion, DTX-PM
      significantly enhanced drug-loading capacity of DTX and had well-reconsitution
      ability, which could be a promising drug delivery system for clinic.

PMID- 22976324
TI  - Novel method for constructing a large-scale design space in lubrication process
      by using Bayesian estimation based on the reliability of a scale-up rule.
AB  - A reliable large-scale design space was constructed by integrating the
      reliability of a scale-up rule into the Bayesian estimation without enforcing a
      large-scale design of experiments (DoE). A small-scale DoE was conducted using
      various Froude numbers (X(1)) and blending times (X(2)) in the lubricant blending
      process for theophylline tablets. The response surfaces, design space, and their
      reliability of the compression rate of the powder mixture (Y(1)), tablet hardness
      (Y(2)), and dissolution rate (Y(3)) on a small scale were calculated using
      multivariate spline interpolation, a bootstrap resampling technique, and self
      organizing map clustering. A constant Froude number was applied as a scale-up
      rule. Experiments were conducted at four different small scales with the same
      Froude number and blending time in order to determine the discrepancies in the
      response variables between the scales so as to indicate the reliability of the
      scale-up rule. Three experiments under an optimal condition and two experiments
      under other conditions were performed on a large scale. The response surfaces on
      the small scale were corrected to those on the large scale by Bayesian estimation
      using the large-scale results and the reliability of the scale-up rule. Large
      scale experiments performed under three additional sets of conditions showed that
      the corrected design space was more reliable than the small-scale design space
      even when there was some discrepancy in the pharmaceutical quality between the
      manufacturing scales. This approach is useful for setting up a design space in
      pharmaceutical development when a DoE cannot be performed at a commercial large
      manufacturing scale.

PMID- 22976325
TI  - Development of a new distyrylbenzene-derivative amyloid-beta-aggregation and
      fibril formation inhibitor.
AB  - Several new amyloid-beta (Abeta) aggregation inhibitors were synthesized
      according to our theory that a hydrophilic moiety could be attached to the Abeta
      recognition unit for the purpose of preventing amyloid plaque formation. A
      distyrylbenzene-derivative, DSB(EEX)(3), which consider the Abeta recognition
      unit (DSB, 1,4-distyrylbenzene) and expected to bind to amyloid fibrils (beta
      sheet structure), was combined with the hydrophilic aggregation disrupting
      element (EEX) (E, Glu; X, 2-(2-(2-aminoethoxy)ethoxy)acetic acid). This
      DSB(EEX)(3) compound, compared to several others synthesized similarly, was found
      to be the most active for reducing Abeta toxicity toward IMR-32 human
      neuroblastoma cells. Moreover, its inhibition of Abeta-aggregation or fibril
      formation was directly confirmed by transmission electron microscopy and atomic
      force microscopy. These results suggest that the Abeta aggregation inhibitor
      DSB(EEX)(3) disrupts clumps of Abeta protein and is a likely candidate for drug
      development to treat Alzheimer's disease.

PMID- 22976326
TI  - The effect of submicron emulsion systems on transdermal delivery of kaempferol.
AB  - In this study, submicron emulsions have been employed as a carrier for the
      topical application of kaempferol. The effect of components of submicron
      emulsions on the physicochemical properties and permeation capability of drug
      were evaluated. In case of drug-loaded submicron emulsions, the cumulative amount
      over 12 h (Q(12 h)), lag time and deposition in skin amount ranged from 13.0+/
      3.4 to 236.1+/-21.2 ug/cm(2), 1.7 to 5.3 h, and 1.10 to 7.76 ug/cm(2),
      respectively, which indicated that the permeation parameters of kaempferol were
      markedly influenced by the component ratio. Kaempferol dispensed in isopropyl
      myristate was used as the control. The Q(12 h), lag time and deposition amount in
      skin were 4.2+/-1.8 ug/cm(2), 6.0 h and 2.25+/-0.60 ug/cm(2), respectively. The
      data showed that used appropriate submicron emulsions as vehicle could
      significantly increase the Q(12 h) and deposition amount in skin and shorten the
      lag time, demonstrating that submicron emulsions have a potent enhancement effect
      for kaempferol transdermal delivery.

PMID- 22976327
TI  - Component crystallization and physical collapse during freeze-drying of L
      arginine-citric acid mixtures.
AB  - Component crystallization and physical collapse during freeze-drying of aqueous
      solutions containing protein-stabilizing L-arginine and citric acid mixtures were
      studied. Freeze-drying microscopy (FDM) and thermal analysis of the solute
      mixture frozen solutions showed collapse onset at temperatures (T(c))
      approximately 10 degrees C higher than their T(g)'s (glass transition
      temperatures of the maximally freeze-concentrated solute phase). Experimental
      freeze-drying of these solutions at a low chamber pressure showed the occurrence
      of physical collapse at shelf temperatures close to or slightly higher than the
      T(c). Slower ice sublimation at higher chamber pressures induced the physical
      collapse from lower shelf temperatures. The large effect of chamber pressures on
      the collapse-inducing shelf temperatures confirmed significance of the
      sublimation-related heat loss on the sublimation interface temperature during the
      primary drying. Drying of the single-solute L-arginine solution resulted in cake
      structure solids composed of its anhydrous crystal. Thermal and powder X-ray
      diffraction (PXRD) analysis suggested slow crystal nucleation of L-arginine
      dihydrate in the frozen solutions. Characterization of the frozen solutions and
      freeze-dried solids should enable rational formulation design and process control
      of amino acid-containing lyophilized pharmaceuticals.

PMID- 22976328
TI  - Characterization of creaming precipitate of tea catechins and caffeine in aqueous
      solution.
AB  - The content of a crude precipitate formed by creaming, which was made from a
      catechin mixture and caffeine, was investigated by an integral volume of H-2
      proton signals of tea catechins in the (1)H-NMR spectrum. Gallated catechins
      formed a crude precipitate more predominantly than non-gallated catechins. The
      2,3-cis-non-gallated catechin (-)-epicatechin (EC) formed a 1:1 complex with
      caffeine, and 2,3-cis-gallated catechin (-)-epicatechin gallate (ECg) formed a
      2:4 complex with caffeine. The pi-pi complexation site of EC with caffeine was
      only the A ring, whereas that of ECg included all aromatic rings, A, B, and B'.
      It was thought that the hydrophobicity of the 2:4 complex of ECg and caffeine was
      stronger than that of the 1:1 complex of EC and caffeine, with the result that
      the 2:4 complex of ECg and caffeine precipitated by creaming more predominantly
      than the 1:1 complex of EC and caffeine in aqueous solution.

PMID- 22976329
TI  - Medicinal flowers. XXXV. Nor-oleanane-type and acylated oleanane-type triterpene
      saponins from the flower buds of Chinese Camellia japonica and their inhibitory
      effects on melanogenesis.
AB  - The methanolic extract and its 1-butanol-soluble fraction from the flower buds of
      Camellia japonica, cultivated in Yunnan Province, China, showed inhibitory
      effects on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. From
      the 1-butanol-soluble fraction, a new 28-nor-oleanane-type and three new oleanane
      type triterpene saponins, sanchakasaponins A-D, were isolated together with four
      known triterpene saponins. Their chemical structures were elucidated on the basis
      of chemical and physicochemical evidence. The inhibitory effects on melanogenesis
      in theophylline-stimulated B16 melanoma 4A5 cells and structure-activity
      relationships of the saponins were investigated.

PMID- 22976330
TI  - Facile synthesis and quantitative structure-activity relationship study of
      antitumor active 2-(4-oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles.
AB  - 2-(5-Arylidene-4-oxo-3-phenyl-thiazolidin-2-ylidene)-3-oxo-propionitriles 4a-j
      were prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a,b.
      The latter was obtained via electrophilic attack of phenylisothiocyanate on 3-oxo
      propionitriles 1a,b followed by reaction with chloroacetyl chloride under basic
      condition. Additionally, 2-(5-heteroalicyclic methylene) analogues 5a-h were
      prepared via Mannich reaction of the appropriate secondary amines and
      formaldehyde with 4-thiazolidinones 3a,b. Many of the synthesized compounds
      exhibited promising antitumor properties against colon HCT116 and breast T47D
      cell lines. 3D-Pharmacophore modeling and quantitative structure-activity
      relationship (QSAR) analysis were combined to explain the observed antitumor
      properties.

PMID- 22976331
TI  - Incompatibility between propericiazine oral solution and tea-based drink.
AB  - Here, we studied the incompatibility between an oral solution of propericiazine
      (PCZ), an antipsychotic drug, and various commercially available bottled tea
      based drinks. When 0.5 mL of the PCZ oral solution (10 mg/mL) was mixed with 16.5
      mL of a tea-based drink (such as green tea, oolong tea, and black tea), the
      residual PCZ content declined to approximately 50% in some mixed solutions. After
      mixing with other tea-based drinks, the residual PCZ content declined to
      approximately 30%, while in others, it changed very little. The residual PCZ
      content declined immediately after mixing with tea-based drinks, but the rate
      remained almost unchanged for the next 24 h. Furthermore, the pH of the mixture
      increased to 4.5-5.1 after the oral solution of PCZ (original pH 3.8) was diluted
      with various tea-based drinks. Afterwards, the pH did not change for 24 h. The
      mixture became cloudy immediately after diluting PCZ oral solution with tea-based
      drinks, and the insoluble substance gradually precipitated. In order to elucidate
      factors responsible for the decline in the content of PCZ, a (-)-epigallocatechin
      gallate solution, which is a main ingredient of green tea polyphenol, was mixed
      with the PCZ oral solution. After mixing, the residual PCZ content declined to
      approximately 60-75%. On the other hand, the content of PCZ did not decline when
      a (-)-epigallocatechin solution was mixed with the PCZ oral solution. The results
      from this study demonstrated that PCZ content was reduced after dilution in tea
      based drinks because of the interaction between PCZ and polyphenol with a galloyl
      group in tea-based drinks.

PMID- 22976332
TI  - Improved method for the solid-phase synthesis of oligoribonucleotide 5'
      triphosphates.
AB  - We have developed an improved solid-phase method for the synthesis of 5'
      triphosphates (5'-TPs) of oligoribonucleotides. The method is based on the use of
      salicyl phosphorochloridite as the phosphitylating reagent and the improvement is
      characterized by the use of the highly reactive pyrophosphorylating reagent
      tris(tetra-n-butylammonium) hydrogen pyrophosphate instead of the conventional
      tri-n-butylammonium salt for the nucleophilic substitution reaction to form the
      cyclic ester intermediate. The improved method can be used to generate
      oligoribonucleotide 5'-TPs efficiently and reproducibly.

PMID- 22976333
TI  - Novel cytotoxic phenanthrenequinone from Odontioda Marie Noel 'Velano'.
AB  - A new phenanthrenequinone, 5-hydroxy-2,3-dimethoxy-1,4-phenanthrenequinone (1),
      was isolated along with a known 9,10-dihydrophenanthrenequinone,
      ephemeranthoquinone B (2) from an MeOH extract of Odontioda Marie Noel 'Velano'
      through bioassay-guided fractionation. Their structures were elucidated by
      spectroscopic analysis, and the compounds were tested for in vitro cytotoxic
      activity. The compounds showed slightly higher cytotoxicity in human oral
      squamous cell carcinoma and leukemic cell lines as compared with human oral
      normal cells. The results suggest that apoptosis may not be involved in the
      cytotoxicity induction.

PMID- 22976334
TI  - A chemo-enzymatic expeditious route to racemic dihexanoyl (2R*,3R*,4R*)
      dehydroxymethylepoxyquinomycin (DHMEQ), the precursor for lipase-catalyzed
      synthesis of the potent nuclear factor-kappaB inhibitor, (2S,3S,4S)-DHMEQ.
AB  - In order to synthesize the potent nuclear factor (NF)-kappaB inhibitor,
      (2S,3S,4S)-dehydroxymethylepoxyquinomycin (DHMEQ), in a large scale, a new route
      for its corresponding racemic precursor, dihexanoyl (2R*,3R*,4R*)-DHMEQ, was
      developed. By employing both hydroquinone and benzoquinone intermediates, the
      total yield, reproducibility, and synthetic steps were improved and the synthetic
      cost was reduced.

PMID- 22976335
TI  - Synthesis of marine diterpene isocyanide (-)-kalihinol Y and diterpene
      isothiocyanate (-)-10-epi-kalihinol I.
AB  - The authors described the first synthesis of diterpene isocyanide (-)-kalihinol Y
      and diterpene isothiocyanate (-)-10-epi-kalihinol I from synthetic intermediates
      of kalihinol A. The absolute structures of these compounds were confirmed by
      these syntheses.

PMID- 22976336
TI  - Spirochaetes and their twisted ways.
AB  - Biological systematists have had a long tradition of encountering organisms that
      are not quite what they seem to be. Among the microbes, horizontal gene transfer
      and evolutionary pressures result in organisms that have distinguished themselves
      from their closest relatives. The recent analyses of several Spirochetes reveal
      members that are not spiral shaped, and ones that appear to have extensively
      acquired genetic material from phylogenetically distant, but environmentally
      proximate, organisms.

PMID- 22976337
TI  - Determinants of negative pathways to care and their impact on service
      disengagement in first-episode psychosis.
AB  - PURPOSE: Although there have been numerous studies on pathways to care in first
      episode psychosis (FEP), few have examined the determinants of the pathway to
      care and its impact on subsequent engagement with mental health services.
      METHODS: Using a sample of 324 FEP patients from a catchment area-based early
      intervention (EI) program in Montreal, we estimated the association of several
      socio-demographic, clinical, and service-level factors with negative pathways to
      care and treatment delay. We also assessed the impact of the pathway to care on
      time to disengagement from EI services. RESULTS: Few socio-demographic or
      clinical factors were predictive of negative pathways to care. Rather, service
      level factors, such as contact with primary care providers, have a stronger
      impact on patterns of health service use across multiple indicators. Patients who
      were in contact with primary care had a reduced likelihood of negative pathways
      to care, but also had longer referral delays to EI services. Socio-demographic
      and clinical factors were more relevant for predicting subsequent engagement with
      EI services, and indicators of negative pathways to care were not associated with
      service disengagement. CONCLUSIONS: Primary care providers may be an efficacious
      target for interventions aimed at reducing overall treatment delay. Increasing
      the uptake of primary care services may also reduce the likelihood of negative
      pathways to care. Our findings draw attention to the need for further
      investigations of the role that the primary care system plays in early
      intervention for FEP, and strategies for supporting service providers in this
      role.

PMID- 22976338
TI  - The prevalence and nature of gambling and problem gambling in South Korea.
AB  - PURPOSE: To establish the current prevalence of gambling and problem gambling in
      South Korea and to determine the associated demographic and game play patterns.
      METHODS: Administration of a gambling survey over the phone to 4,000 randomly
      selected South Korean adults (19+), supplemented by an online survey of 4,330
      members of a South Korean online panel. RESULTS: The past year prevalence of
      gambling among South Korean adults was 41.8 %. The past year engagement in
      individual forms of gambling was 36.2 % for lotteries and instant lotteries; 12.0
      % for social gambling; 2.3 % for sports betting; 1.5 % for casino gambling; 1.5 %
      for internet gambling; and 1.1 % for horse, bicycle, or motor boat betting. The
      past year prevalence of problem gambling was 0.5 %. Logistic regression
      identified the best predictors of problem gambling to be: having a greater number
      of gambling fallacies; gambling on the internet; betting on horses, bicycling, or
      motor boat racing; social gambling; male gender; mental health problems; sports
      betting; motivation for gambling (gambling to escape); casino gambling; and lower
      income. CONCLUSIONS: The past year prevalence of gambling (41.8 %) and problem
      gambling (0.5 %) in South Korea is low compared to other countries, especially
      relative to other Asian jurisdictions. This relatively low prevalence of gambling
      is likely related to the very strong negative attitudes toward it, the low
      participation by females, and restricted access. The low prevalence of problem
      gambling is likely related to the relatively low prevalence of gambling and
      restricted access to continuous forms of gambling. The variables that are
      predictive of problem gambling in South Korea are quite similar to those found in
      other countries with a couple of important differences.

PMID- 22976339
TI  - Rational approaches to improving the isolation of endophytic actinobacteria from
      Australian native trees.
AB  - In recent years, new actinobacterial species have been isolated as endophytes of
      plants and shrubs and are sought after both for their role as potential producers
      of new drug candidates for the pharmaceutical industry and as biocontrol
      inoculants for sustainable agriculture. Molecular-based approaches to the study
      of microbial ecology generally reveal a broader microbial diversity than can be
      obtained by cultivation methods. This study aimed to improve the success of
      isolating individual members of the actinobacterial population as pure cultures
      as well as improving the ability to characterise the large numbers obtained in
      pure culture. To achieve this objective, our study successfully employed rational
      and holistic approaches including the use of isolation media with low
      concentrations of nutrients normally available to the microorganism in the plant,
      plating larger quantities of plant sample, incubating isolation plates for up to
      16 weeks, excising colonies when they are visible and choosing Australian endemic
      trees as the source of the actinobacteria. A hierarchy of polyphasic methods
      based on culture morphology, amplified 16S rRNA gene restriction analysis and
      limited sequencing was used to classify all 576 actinobacterial isolates from
      leaf, stem and root samples of two eucalypts: a Grey Box and Red Gum, a native
      apricot tree and a native pine tree. The classification revealed that, in
      addition to 413 Streptomyces spp., isolates belonged to 16 other actinobacterial
      genera: Actinomadura (two strains), Actinomycetospora (six), Actinopolymorpha
      (two), Amycolatopsis (six), Gordonia (one), Kribbella (25), Micromonospora (six),
      Nocardia (ten), Nocardioides (11), Nocardiopsis (one), Nonomuraea (one),
      Polymorphospora (two), Promicromonospora (51), Pseudonocardia (36), Williamsia
      (two) and a novel genus Flindersiella (one). In order to prove novelty, 12
      strains were characterised fully to the species level based on polyphasic
      taxonomy. One strain represented a novel genus in the family Nocardioides, and
      the other 11 strains were accepted as novel species. In summary, the holistic
      isolation strategies were successful in obtaining significant culturable
      actinobacterial diversity within Australian native trees that includes rare and
      novel species.

PMID- 22976342
TI  - Japanese professional nurses spend unnecessarily long time doing nursing
      assistants' tasks.
AB  - In environments in which professional nurses do simple tasks, e.g., laundry,
      cleaning, and waste disposal, they cannot concentrate on technical jobs by
      utilizing their expertise to its fullest benefit. Particularly, in Japan, the
      nursing shortage is a serious problem. If professional nurses take their time to
      do any of these simple tasks, the tasks should be preferentially allocated to
      nursing assistants. Because there has been no descriptive study to investigate
      the amount of time Japanese professional nurses spent doing such simple tasks
      during their working time, their actual conditions remain unclear. Professional
      nurses recorded their total working time and the time they spent doing such
      simple tasks during the week of the survey period. The time an individual
      respondent spent doing one or more simple tasks during that week was summed up,
      as was their working time. Subsequently, the percentage of the summed time he or
      she spent doing any of those tasks in his or her summed working time was
      calculated. A total of 1,086 respondents in 19 hospitals that had 87 to 376 beds
      were analyzed (response rate: 53.3%). The average time (SD) that respondents
      spent doing those simple tasks and their total working time were 2.24 (3.35)
      hours and 37.48 (10.88) hours, respectively. The average percentage (SD) of the
      time they spent doing the simple tasks in their working time was 6.00% (8.39).
      Hospital administrators must decrease this percentage. Proper working
      environments in which professional nurses can concentrate more on their technical
      jobs must be created.

PMID- 22976340
TI  - Culture-dependent and independent studies of microbial diversity in highly copper
      contaminated Chilean marine sediments.
AB  - Cultivation and molecular-based approaches were used to study microbial diversity
      in two Chilean marine sediments contaminated with high (835 ppm) and very high
      concentrations of copper (1,533 ppm). The diversity of cultivable bacteria
      resistant to copper was studied at oxic and anoxic conditions, focusing on
      sulfate-, thiosulfate-, and iron-reducing bacteria. For both sediments, the
      cultivable bacteria isolated at oxic conditions were mostly affiliated to the
      genus Bacillus, while at anoxic conditions the majority of the cultivable
      bacteria found were closely related to members of the genera Desulfovibrio,
      Sphingomonas, and Virgibacillus. Copper resistance was between 100 and 400 ppm,
      with the exception of a strain affiliated to members of the genus Desulfuromonas,
      which was resistant up to 1,000 ppm of copper. In parallel, cloning and
      sequencing of 16S rRNA was performed to study the total bacterial diversity in
      the sediments. A weak correlation was observed between the isolated strains and
      the 16S rRNA operational taxonomic units detected. The presence of copper
      resistance genes (copA, cusA, and pcoA) was tested for all the strains isolated;
      only copA was detected in a few isolates, suggesting that other copper resistance
      mechanisms could be used by the bacteria in those highly copper-contaminated
      sediments.

PMID- 22976343
TI  - Estimating young Australian adults' risk of hearing damage from selected leisure
      activities.
AB  - OBJECTIVE: Several previous studies have attempted to estimate the risk of noise
      induced hearing loss from loud leisure noise. Some of these studies may have
      overestimated the risk because they used noise estimates taken from the higher
      end of reported levels. The aim of the present study was to provide a realistic
      estimate of the number of young Australian adults who may be at risk of hearing
      damage and eventual hearing loss from leisure-noise exposure. DESIGN: Average
      noise levels at five high-noise leisure activities, (1) nightclubs; (2) pubs,
      bars, and registered clubs; (3) fitness classes; (4) live sporting events; (5)
      concerts and live music venues, were calculated using 108 measurements taken from
      a large database of leisure noise measurements. In addition, an online survey was
      administered to a convenience sample of 1000 young adults aged 18 to 35 years,
      who reported the time spent at these leisure activities and the frequency with
      which they undertook the activities. They also answered questions about tinnitus
      and their perceived risk of hearing damage. Although the survey data cannot be
      considered representative of the population of young Australian adults, it was
      weighted to this population in respect of age, gender, education, and location.
      The survey data and the average noise levels were used to estimate each
      individual's annual noise exposure, and in turn, estimate those at risk of
      hearing damage from leisure-noise exposure. RESULTS: For the majority of
      participants (n = 868), the accumulated leisure noise level was within the
      acceptable workplace limit. However, 132 participants or 14.1% (population
      weighted) were exposed to an annual noise dose greater than the acceptable
      workplace noise limit. By far, the main source of high-risk leisure noise was
      from nightclubs. Those with more leisure-noise exposure experienced more tinnitus
      and perceived themselves to be more at risk than those with lower noise
      exposures. CONCLUSIONS: It is recommended that nightclub operators reduce noise
      levels, display warnings, and provide earplugs for patrons and employees. Health
      promoters should focus their attention on those young adults who are most at risk
      and provide them with targeted practical advice about reducing their leisure
      noise exposure and avoiding hearing loss.

PMID- 22976344
TI  - Clinical observation on acute low-frequency hearing loss without vertigo:  the
      role of cochlear hydrops analysis masking procedure as initial prognostic
      parameter.
AB  - OBJECTIVES: Even though it is currently not possible to prove a pathological
      diagnosis for inner ear disease, acute low-frequency hearing loss (ALFHL) without
      vertigo could be caused by inner ear hydrops because progression into the
      clinical spectrum of endolymphatic hydrops (EH) frequently occur among patients
      with the initial clinical presentation. Therefore, audiological measures
      representative of inner ear hydrops, such as the cochlear hydrops analysis
      masking procedure (CHAMP) test, may be used to predict the prognosis of ALFHL
      without vertigo. To test this hypothesis, we prospectively investigated patients
      with ALFHL unaccompanied by vertigo and examined whether the CHAMP test generated
      more useful information for prediction of progression into clinical spectrum of
      EH compared with other neurotologic parameters. DESIGN: A prospective clinical
      study of 28 patients who initially presented with ALFHL without vertigo was
      conducted. Detailed neurotologic findings from pure-tone audiometry,
      electrocochleography, CHAMP, spontaneous nystagmus, head-shaking nystagmus,
      vibration-induced nystagmus, the bithermal caloric test, and the rotatory chair
      test were recorded at the time of initial presentation. A regular audiological
      and clinical examination was conducted until either the last follow-up at our
      clinic or on the day on which secondary audiovestibular symptoms occurred. The
      rates of progression to Meniere's disease (MD) or clinical presentation
      compatible with isolated cochlear hydrops during the study period were calculated
      by the log-rank test and relative risk. A receiver operating characteristics
      curve was plotted to determine the prognostic value of CHAMP. RESULTS: Of 28
      patients, 15 (53%) showed improvement in hearing on pure-tone audiometry. Seven
      patients (25%) showed hearing fluctuation and nine (32%) developed a vertigo
      attack during the observation period. Of these, three patients experienced both
      vertigo and a hearing fluctuation. Abnormal results of electrocochleography and
      neurotologic tests reflecting vestibular ocular reflex on yaw plane were common
      at the time of diagnosis of ALFHL in many patients, but these parameters were not
      associated with an increased risk of progression of clinical spectrum of EH. In
      contrast, patients with an abnormal complex amplitude ratio (CAR) on CHAMP had a
      2.6-fold increased risk of progression to a clinical spectrum of EH (either
      hearing fluctuation or MD). The hazard ratio of developing MD for patients with
      normal CAR as compared with those with an abnormal CAR was 0.137 (95% confidence
      interval 0.03-0.57; p < 0.001), which indicates an 84.3% reduced risk of
      developing MD in those with normal CAR. A CAR value of 0.975 or less indicated
      the possibility of developing either a hearing fluctuation or vertiginous episode
      with a sensitivity of 82% and a specificity of 73% by receiver operating
      characteristics curve analysis. CONCLUSIONS: The results of the study suggest
      that CHAMP measurement may be useful for determining the prognosis of patients
      with ALFHL without vertigo. A CAR value of 0.975 or less indicates the
      possibility of developing fluctuating hearing loss or vertigo in patients with
      ALFHL unaccompanied by vertigo.

PMID- 22976345
TI  - A case of spinal tuberculosis from the middle ages in Transylvania (Romania).
AB  - STUDY DESIGN: Case report. OBJECTIVE: To characterize the paleopathology
      presented in the skeleton of a 45- to 50-year-old man indicative of tuberculous
      spondylitis and to confirm by the detection of ancient DNA. SUMMARY OF BACKGROUND
      DATA: Tuberculosis (TB) is an infectious disease prevalent in both present and
      ancient human populations. The disease is primarily located within the lungs;
      although characteristic bone lesions can lead to a clear diagnosis, skeletal TB
      occurs in only 5% to 6% of TB infections, even in historical cases. In addition,
      the visual appearance of human skeletal remains may be influenced by the
      environmental conditions at the burial site. However, it is important to
      recognize ancient skeletal TB because it can provide important data on the
      history of Mycobacterium tuberculosis and give a unique opportunity for
      physicians to observe the natural outcome of the infection of the preantibiotic
      era. METHODS: Paleopathological analysis was carried out using careful visual
      observation supported by ancient DNA analysis. Approximately 60 mg of bone powder
      from rib fragments was examined and DNA from the M. tuberculosis complex was
      detected by polymerase chain reaction (PCR) targeting specific genetic loci of
      the IS6110 and IS1081 regions. RESULTS: The skeleton is part of a human
      osteoarchaeological collection (n = 274) from the 12th- to 13th-century
      Transylvanian archaeological site of Peteni, in modern-day Romania. The
      individual, a 45- to 50-year-old man, showed gross pathology typical of
      tuberculous spondylitis. The paleopathological diagnosis was supported by
      analysis for M. tuberculosis complex ancient DNA. CONCLUSIONS: This case
      demonstrates that TB was present in Transylvania (Romania) during the 12th and
      13th centuries and adds to the growing body of knowledge on the history of this
      disease.

PMID- 22976346
TI  - Characteristics of diabetes associated with poor improvements in clinical
      outcomes after lumbar spine surgery.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: Evaluation of the impact of
      diabetes on lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Characteristics of
      diabetes that increase the risk of postoperative complications and poor surgical
      outcomes after lumbar spine surgery remain unclear. METHODS: The demographic and
      clinical data of diabetic and nondiabetic patients, 50 years or older, undergoing
      lumbar spine surgery were reviewed. Japanese Orthopaedic Association and visual
      analogue scale scores for low back pain, leg pain, and numbness were assessed as
      perioperative outcomes. Analysis of covariance was used for comparison of
      perioperative outcomes to adjust for differences between the groups, and a
      proportional odds model was used to compute the odds ratio of poor improvement in
      each outcome. RESULTS: Forty-one patients with diabetes were compared with 124
      patients without diabetes. Visual analogue scale scores of final low back pain
      was higher for patients with than without diabetes (29.3 vs. 17.9, P = 0.013).
      Complications were similar in patients with and without diabetes except for
      nonunion after fusion surgery (20% vs. 3%, P = 0.095). When stratified by
      surgical procedure, final low back pain was significantly higher for patients
      with diabetes who underwent fusion surgery (39.1 vs. 17.4, P = 0.001). Patients
      with glycosylated hemoglobin of 6.5% or more displayed a 2-fold increase only in
      the odds ratio (OR) of poor improvement of low back pain (OR = 2.37; 95%
      confidence interval [CI], 0.99-5.70). Patients having diabetes for 20 years or
      more were more likely to experience poor improvement of low back pain and leg
      numbness (OR = 4.95; 95% CI, 1.69-14.5 and OR = 2.80; 95% CI, 0.98-7.94,
      respectively). Insulin use was associated with an increased OR for poor
      improvement of leg numbness (OR = 4.49; 95% CI, 1.24-16.3). CONCLUSION:
      Longstanding diabetes, poor glycemic control, and insulin use might be associated
      with poor postoperative improvement.

PMID- 22976347
TI  - Critical dynamics in host-pathogen systems.
AB  - Host-pathogen interactions provide a fascinating example of two or more active
      genomes directly exerting mutual influence upon each other. These encounters can
      lead to multiple outcomes from symbiotic homeostasis to mutual annihilation,
      undergo multiple cycles of latency and lysogeny, and lead to coevolution of the
      interacting genomes. Such systems pose numerous challenges but also some
      advantages to modeling, especially in terms of functional, mathematical genome
      representations. The main challenges for the modeling process start with the
      conceptual definition of a genome for instance in the case of host-integrated
      viral genomes. Furthermore, hardly understood influences of the activity of
      either genome on the other(s) via direct and indirect mechanisms amplify the
      needs for a coherent description of genome activity. Finally, genetic and local
      environmental heterogeneities in both the host's cellular and the pathogen
      populations need to be considered in multiscale modeling efforts. We will review
      here two prominent examples of host-pathogen interactions at the genome level,
      discuss the current modeling efforts and their shortcomings, and explore novel
      ideas of representing active genomes which promise being particularly adapted to
      dealing with the modeling challenges posed by host-pathogen interactions.

PMID- 22976348
TI  - One Health and emerging infectious diseases: clinical perspectives.
AB  - To date, there has been little articulation of specific One Health clinical
      activities for veterinary and human health care providers regarding emerging
      infectious diseases, yet they could play a critical role. Under current clinical
      paradigms, both human and animal health professionals routinely diagnose and
      treat zoonotic infectious diseases in their patients, but tend to work in
      parallel with little cross-professional communication or coordination of care.
      For this to evolve toward a One Health model, both types of clinicians need to
      see how individual cases can be "sentinel events" indicating environmental risk
      for disease emergence, and develop mechanisms of rapid communication about these
      risks. Human and animal clinicians also need to take a more proactive and
      preventive approach to zoonotic diseases that includes the occupational health of
      animal workers in farms, laboratories, veterinary clinics, and other settings, as
      well as the recognition of increased risk among immunocompromised individuals in
      contact with animals. This requires training in One Health clinical competencies
      including the ability to diagnose and treat zoonotic diseases, implement
      preventive care interventions for individual patients, provide occupational
      health services for animal workers, recognize sentinel cases, report cases to
      public heath and clinical colleagues, and assess and help to intervene with
      environmental factors driving infectious disease risk in humans and animals. To
      provide an evidence base for such competency training, there is a need for
      development and testing of innovative protocols for One Health clinical
      collaborations. 

PMID- 22976349
TI  - Bovine spongiform encephalopathy: a tipping point in One Health and Food Safety.
AB  - Bovine spongiform encephalopathy (BSE) is a protein misfolding disease of cattle
      which belongs to the group of transmissible spongiform encephalopathies (TSEs) or
      prion diseases. This group also includes scrapie in sheep and goats, chronic
      wasting disease (CWD) of cervids and Creutzfeldt-Jakob disease (CJD) humans. The
      first case of BSE was recognised in England in 1986 as a progressive,
      neurological condition where affected animals behaved abnormally, exhibited
      anxiety, ataxia, hypersensitivity to touch and noise and poor body condition.
      Spongiform change was observed in the brain stem of cattle at post-mortem and its
      similarity to scrapie in sheep stimulated biochemical investigation and
      transmission studies which confirmed it as a novel prion disease of cattle.
      Epidemiological analysis of the initial cases of disease implicated a common
      extended source of infection, likely to be related to feed, and stimulated a
      series of control measures designed to restrict feeding of mammalian-derived
      protein to ruminants in various parts of the United Kingdom and to prevent the
      use of various bovine offals in feed or food production. This article outlines
      the rise and fall of the incidence of BSE in the UK and Europe, its
      classification as a zoonotic disease with the emergence of variant CJD, the
      implications of it as a prion disease and challenge its diagnosis and control
      continues to represent worldwide. 

PMID- 22976350
TI  - Swine influenza virus vaccines: to change or not to change-that's the question.
AB  - Commercial vaccines currently available against swine influenza virus (SIV) are
      inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or
      H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs
      circulating in Europe and the US, the vaccines for each region are produced
      locally and contain different strains. Even within a continent, there is no
      standardization of vaccine strains, and the antigen mass and adjuvants can also
      differ between different commercial products. Recombinant protein vaccines
      against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse
      genetics have been tested in experimental studies, but they have not yet reached
      the market. In this review, we aim to present a critical analysis of the
      performance of commercial inactivated and novel generation SIV vaccines in
      experimental vaccination challenge studies in pigs. We pay special attention to
      the differences between commercial SIV vaccines and vaccination attitudes in
      Europe and in North America, to the issue of vaccine strain selection and
      changes, and to the potential advantages of novel generation vaccines over the
      traditional killed SIV vaccines.

PMID- 22976351
TI  - Lifestyle changes in women at genetic risk of breast cancer: an observational
      study.
AB  - BACKGROUND: Lifestyle influences breast cancer risk. Women at increased familial
      risk may benefit from modifying behaviour, but it is not known to what extent
      they do so. PURPOSE: This study aims to measure changes that UK (Scottish) women
      make in response to increased familial risk of breast cancer and attitudes to a
      risk-reduction trial. METHODS: A questionnaire, completed by 140 "breast cancer
      family" clinic patients, generated data on habitual diet, alcohol consumption and
      exercise, changes made after learning of breast cancer risk and attitudes to
      possible further changes. Subgroups of patients were defined by criteria likely
      to influence changes in behaviour. Between-group differences were analysed by
      Fisher's exact test and overall correlations by linear regression. RESULTS:
      Thirty-six subjects (26 %) reported no behavioural change but, overall, around 25
      % of diet, exercise and alcohol items had been changed. Women perceiving their
      lifetime cancer risk to be high (>50 %) and those who were obese (BMI >25) had
      made significantly more changes than others. Younger women (<40 years) and those
      with daughters had made fewer changes. Almost all suggested elements of a risk
      reduction trial were strongly supported. CONCLUSIONS: Scottish women at increased
      risk of breast cancer have scope for protective changes in lifestyle and support
      a risk-reduction trial. The needs of younger women and of those with daughters
      should be addressed in its design.

PMID- 22976352
TI  - Dual fluorescence detection of protein and RNA in Drosophila tissues.
AB  - Detection of RNAs by in situ hybridization (ISH) is a well-established technique
      that permits the study of specific RNA expression patterns in tissues; however,
      not all tissues are equally amenable to staining using the same procedure. Here
      we describe a protocol that combines whole-mount immunofluorescence (IF) and
      fluorescence in situ hybridization (FISH) for the simultaneous detection of
      specific RNA transcripts and proteins, greatly enhancing the spatial resolution
      of RNA expression in complex, intact fly tissues. To date, we have successfully
      used this protocol in adult testis, larval male gonads, adult intestine and
      Malpighian tubules. IF is conducted in RNase-free solutions, prior to the harsh
      conditions of FISH, in order to preserve protein antigenicity within dissected
      tissues. Separate protocols are described for mRNA and miRNA detection, which are
      based on robust digoxigenin (DIG) RNA and locked nucleic acid (LNA) probes,
      respectively. The combined IF-FISH procedure can be completed in 2 d for miRNA
      detection and 4 d for mRNA detection. Although optimized for Drosophila, this IF
      FISH protocol should be adaptable to a wide variety of organisms, tissues,
      antibodies and probes, thus providing a reliable and simple means to compare RNA
      and protein abundance and localization.

PMID- 22976353
TI  - LOTOS-based two-photon calcium imaging of dendritic spines in vivo.
AB  - Neurons in the mammalian brain receive thousands of synaptic inputs on their
      dendrites. In many types of neurons, such as cortical pyramidal neurons,
      excitatory synapses are formed on fine dendritic protrusions called spines.
      Usually, an individual spine forms a single synaptic contact with an afferent
      axon. In this protocol, we describe a recently established experimental procedure
      for measuring intracellular calcium signals from dendritic spines in cortical
      neurons in vivo by using a combination of two-photon microscopy and whole-cell
      patch-clamp recordings. We have used mice as an experimental model system, but
      the protocol may be readily adapted to other species. This method involves data
      acquisition at high frame rates and low-excitation laser power, and is termed low
      power temporal oversampling (LOTOS). Because of its high sensitivity of
      fluorescence detection and reduced phototoxicity, LOTOS allows for prolonged and
      stable calcium imaging in vivo. Key aspects of the protocol, which can be
      completed in 5-6 h, include the use of a variant of high-speed two-photon
      imaging, refined surgery procedures and optimized tissue stabilization.

PMID- 22976354
TI  - Determining proteome-wide expression levels using reverse protein arrays in
      fission yeast.
AB  - Global protein expression profiling of various mutants or growth conditions is
      currently a major challenge in biology. Here we provide a protocol for a strategy
      that we recently developed that couples ORFeome-based (ORF denotes open reading
      frame) expression to reverse protein arrays; this approach accurately quantifies
      more than 99% of the predicted fission yeast proteins in various genetic
      backgrounds. The first stage of this two-stage protocol requires mass mating
      between any fertile fission yeast mutant of interest and the integrated fission
      yeast-tagged ORFeome followed by selection of recombinant haploids. The second
      stage of the protocol, called reverse protein arrays, involves simple large-scale
      extraction of total proteins, which are then spotted on nitrocellulose membranes
      for detection by quantitative dot blot. When handled manually, the entire
      protocol takes about 2 months. However, the process could easily be automated and
      should also be applicable to other organisms.

PMID- 22976355
TI  - Directed differentiation of human pluripotent stem cells to cerebral cortex
      neurons and neural networks.
AB  - Efficient derivation of human cerebral neocortical neural stem cells (NSCs) and
      functional neurons from pluripotent stem cells (PSCs) facilitates functional
      studies of human cerebral cortex development, disease modeling and drug
      discovery. Here we provide a detailed protocol for directing the differentiation
      of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs)
      to all classes of cortical projection neurons. We demonstrate an 80-d, three
      stage process that recapitulates cortical development, in which human PSCs
      (hPSCs) first differentiate to cortical stem and progenitor cells that then
      generate cortical projection neurons in a stereotypical temporal order before
      maturing to actively fire action potentials, undergo synaptogenesis and form
      neural circuits in vitro. Methods to characterize cortical neuron identity and
      synapse formation are described.

PMID- 22976356
TI  - Outcomes of wrist arthroplasty using a free vascularized fibular head graft for
      Enneking stage II giant cell tumors of the distal radius.
AB  - The purpose of this study was to report the clinical outcomes of wrist
      arthroplasty with a free vascularized fibular head graft (FVFHG) and to highlight
      some considerations that may affect outcomes. FVFHG was performed on 12 patients
      with giant cell tumors of the distal radius between April 1984 and July 2005. The
      mean age of patients was 33 years. All 12 patients were classified as Enneking
      stage 2. Outcomes were evaluated with radiographic and functional assessments,
      including the scale of Enneking. The mean follow-up period was 6.26 years. Bone
      union was achieved in all patients at a mean of 15.7 weeks after surgery. Skin
      grafting was performed at the recipient site in 5 patients and had good skin
      healing. Subluxation in the wrist joint was observed in 5 patients and was
      related to the length of the transplanted fibula. The 5 patients with subluxation
      experienced considerable osteoarthritic change. The mean arc of flexion-extension
      and rotation of the wrist joint was 73.1 degrees  and 102.9 degrees ,
      respectively. The mean grip strength was 57.25% of the contralateral side. The
      mean functional score was 26.4 points. Wrist arthroplasty with a FVFHG is a
      useful option to treat Enneking stage 2 giant cell tumors of the distal radius.
      We believe that wrist instability is not determined by the choice of laterality
      of the fibula, which can be minimized by transplanting a short fibula with the
      anterior tibial artery as a donor artery. The recipient sites can be successfully
      resurfaced by skin grafting.

PMID- 22976357
TI  - Primary care: health care's leading edge, part II.

PMID- 22976358
TI  - Primary care and health reform.
AB  - Skyrocketing health care costs are burdening our people and our economy, yet
      health care indicators show how little we are achieving with the money we spend.
      Federal and state governments, along with public-health experts and policymakers,
      are proposing a host of new initiatives to find solutions. The Patient Protection
      and Affordable Care Act is designed to address both the quality and accessibility
      of health care, while reducing its cost. This article provides an overview of
      models supported by the Affordable Care Act that address one or more goals of the
      "Triple Aim": better health care for individuals, better health outcomes in the
      community, and lower health care costs. The models described below rely on the
      core principles of primary care: comprehensive, coordinated and continuous
      primary care; preventive care; and the sophisticated implementation of health
      information technology designed to promote communication between health care
      providers, enhance coordination of care, minimize duplication of services, and
      permit reporting on quality. These models will support better health care and
      reduced costs for people who access health care services but will not address
      health outcomes in the community at large. Health care professionals, working in
      concert with community-based organizations and advocates, must also address
      conditions that influence health in the broadest sense to truly improve the
      health of our communities and reduce health care costs.

PMID- 22976359
TI  - Improving transitions of care from hospital to home: what works?
AB  - As the cost of care rises and fragmentation of health care increases, care
      transitions have become critical parts of the health care system. Physicians and
      other inpatient providers have the responsibility to communicate to subsequent
      providers, but such communication occurs far less than is optimal. Timely
      discharge summaries for the next-level provider, postdischarge phone calls to
      patients, and postdischarge follow-up appointments with primary-care physicians
      or inpatient providers may improve postdischarge health care utilization.
      Pharmacists may also reduce medication errors, adverse medication events, and
      even readmissions. The most promising data, however, come from studies of
      multidisciplinary approaches, some of which have shown large reductions in
      postdischarge utilization and costs. More study is needed to pinpoint the most
      cost-effective and efficient strategies to improve transitions from the inpatient
      setting to other settings.

PMID- 22976360
TI  - Evidence-based medicine and primary care: keeping up is hard to do.
AB  - Primary-care physicians feel pressure to be knowledgeable, efficient,
      comprehensive, and compassionate while delivering evidence-based medical care.
      Incorporating evidence-based medicine into practice requires training in the
      skills of finding and applying good evidence to patients, and, increasingly,
      infrastructure that supports the incorporation of evidence into electronic health
      records. Physicians cite many barriers to the use of evidence-based medicine in
      practice. In this review, we examine evidence of the value of evidence-based
      medicine in clinical practice, discuss the interface of evidence and shared
      decision-making, suggest tools and approaches for incorporating evidence-based
      medicine into practice, and discuss the impact of recent health insurance reform
      on expectations and incentives for physicians with respect to evidence-based
      practice.

PMID- 22976361
TI  - Gender disparities in health care.
AB  - The existence of disparities in delivery of health care has been the subject of
      increased empirical study in recent years. Some studies have suggested that
      disparities between men and women exist in the diagnoses and treatment of health
      conditions, and as a result measures have been taken to identify these
      differences. This article uses several examples to illustrate health care gender
      bias in medicine. These examples include surgery, peripheral artery disease,
      cardiovascular disease, critical care, and cardiovascular risk factors.
      Additionally, we discuss reasons why these issues still occur, trends in health
      care that may address these issues, and the need for acknowledgement of the
      current system's inequities in order to provide unbiased care for women in the
      future.

PMID- 22976362
TI  - Health maintenance in older adults: combining evidence and individual
      preferences.
AB  - There is increasing interest in maintaining health and delaying disability for
      older adults as this population segment expands. And instead of focusing on a
      traditional disease-specific approach to health maintenance, there is an ongoing
      shift to a patient-centered approach, and defining outcomes based on the older
      adults' goals. In this approach, their goals and preferences are central, and
      other factors such as their health status and prognosis help determine which
      goals may be realistic. These subjective goals and objective characteristics are
      then balanced with the risks, benefits, and harms of established evidence-driven
      health-maintenance recommendations. Hence, older adults share their goals and
      preferences with clinicians; while clinicians share information on risks,
      benefits, harms, and uncertainties of existing health-maintenance
      recommendations, and help guide the older adult through how existing evidence can
      respond to their health goals and preferences. In this article, the concept of
      patient-centered care in the context of health maintenance for older adults is
      discussed; and health maintenance recommendations for older adults are reviewed.

PMID- 22976363
TI  - Integrating palliative care into primary care.
AB  - Patients with serious illnesses are living longer and with greater disabilities.
      Palliative-care interventions have been shown to increase quality of life, lower
      costs, and improve survival. In order to meet the palliative-care needs of
      patients, it is crucial for primary-care clinicians to understand how they can
      provide primary palliative care and when they should refer to palliative-care
      specialists. By working together, many more patients and families will receive
      the comprehensive, individualized, coordinated care and support that both primary
      care and palliative care offers to patients. This article will review literature
      illustrating the benefits of palliative care; discuss why primary-care clinicians
      are ideally suited to incorporate palliative care into their practice; and
      provide guidance to primary-care clinicians regarding how and when to access
      palliative-care specialist services, how to gain more training in palliative
      care, and how to be reimbursed for palliative-care visits.

PMID- 22976364
TI  - Health care for homeless and unstably housed: overcoming barriers.
AB  - The causes of homelessness are complex and multifactorial and the solutions
      equally complex. Though homelessness is not a disease process, it is directly
      linked to poor health outcomes. It is thus incumbent on health care professionals
      to know the various definitions of homelessness, the ramifications of unstable
      housing, and the specific living conditions of each homeless patient. These
      factors needed to be accounted for when designing treatment plans in a way that
      will increase access to care and promote adherence. Increasing compliance and
      addressing barriers to care will improve outcomes and may reduce overall health
      expenditures.

PMID- 22976365
TI  - Personal health records: meaningful use, but for whom?
AB  - Providers and hospitals have received more than $5 billion from the federal
      government for meaningfully using electronic health records as of April 2012.
      Meaningful Use stage 1 makes adoption of the personal health record optional. The
      proposed Meaningful Use stage 2 regulations make personal health record use
      mandatory. There is peer-reviewed literature to support a personal health record
      adoption rate of 10%, which is optional in stage 1 and required in stage 2. The
      literature also supports the use of secure messaging required in stage 2.
      However, there is little evidence to support other stage 2 personal health record
      requirements and dependencies. Further study is urgently needed to ensure that
      Meaningful Use stage 2 is meaningful for both patients and providers.

PMID- 22976366
TI  - Family medicine: a specialty for all ages.
AB  - After a diminishing of its ranks following the post-World War II explosion of
      growth in medical discoveries, advanced medical technology, and the concomitant
      specialization of the physician workforce, family medicine is re-establishing
      itself as a leading medical specialty that has garnered growing interest among
      recent medical-school graduates. Family physicians provide care for patients of
      all ages, from newborns to the elderly. In addition to its wide scope of
      practice, family medicine is characterized by its emphasis on understanding of
      the whole person, its partnership approach with patients over many years, and its
      command of medical complexity. Family physicians are trained both to use
      community resources to assist individual patients in meeting medical or social
      needs and to identify and address community-wide needs. The specialty of family
      medicine is uniquely positioned to provide a leadership role in health-reform
      efforts that are accelerating across the country. Health care models that are
      gaining traction, such as the patient-centered medical home model, health homes,
      and accountable care organizations, share the characteristics of providing
      comprehensive, coordinated patient care with an emphasis on disease prevention
      and health promotion. This model of care, provided in the context of family and
      community, has been the hallmark of family medicine since its creation as a
      distinct medical specialty more than 40 years ago. In addition, family
      physicians' ability to care for patients of all ages make them particularly cost
      effective as the new models of care move to improve access to care through
      expanded hours and locations.

PMID- 22976367
TI  - Meyerhoff Scholars Program: a strengths-based, institution-wide approach to
      increasing diversity in science, technology, engineering, and mathematics.
AB  - The Meyerhoff Scholars Program at the University of Maryland, Baltimore County is
      widely viewed as a national model of a program that enhances the number of
      underrepresented minority students who pursue science, technology, engineering,
      and mathematics PhDs. The current article provides an overview of the program and
      the institution-wide change process that led to its development, as well as a
      summary of key outcome and process evaluation research findings. African American
      Meyerhoff students are 5* more likely than comparison students to pursue a
      science, technology, engineering, and mathematics PhD. Program components viewed
      by the students as most beneficial include financial scholarship, being a part of
      the Meyerhoff Program community, the Summer Bridge program, study groups, and
      summer research. Qualitative findings from interviews and focus groups
      demonstrate the importance of the Meyerhoff Program in creating a sense of
      belonging and a shared identity, encouraging professional development, and
      emphasizing the importance of academic skills. Among Meyerhoff students, several
      precollege and college factors have emerged as predictors of successful entrance
      into a PhD program in the science, technology, engineering, and mathematics
      fields, including precollege research excitement, precollege intrinsic
      math/science motivation, number of summer research experiences during college,
      and college grade point average. Limitations of the research to date are noted,
      and directions for future research are proposed.

PMID- 22976368
TI  - Hypocalcaemia after total thyroidectomy for Graves' disease and for benign atoxic
      multinodular goitre.
AB  - PURPOSE: Postoperative hypocalcaemia has been reported to be more common after
      total thyroidectomy (TT) for Graves' disease than after TT for benign atoxic
      multinodular goitre (MNG). The reasons for this potential association are not
      clear. In the present study, the frequency and risk factors of hypocalcaemia
      after TT for Graves' vs MNG were compared. METHODS: Between January 1999 and
      October 2009, patients with first-time surgery for Graves' disease or MNG treated
      with a TT were included in the study. Postoperative hypocalcaemia was defined by
      symptoms, calcium levels and treatment with calcium and/or vitamin D analogues
      during postoperative hospital stay, at discharge, and at the 6-week and 6-month
      follow-ups. Outcomes were compared with Mann-Whitney, chi(2) and Fishers' exact
      test where appropriate and by multivariable logistic regression analysis.
      RESULTS: There were 128 patients with Graves' disease and 81 patients with MNG.
      Patients with Graves' disease were younger than patients with MNG (median age, 35
      vs 51 years, p < 0.001). Symptoms of hypocalcaemia were more common in patients
      with Graves' disease (p < 0.001; OR, 95 % CI 3.26, 1.48-7.14), but the frequency
      of biochemical hypocalcaemia, postoperative levels of parathyroid hormone (PTH)
      and treatment with calcium and vitamin D did not differ between groups of
      patients. CONCLUSION: Apart from more frequent symptoms of hypocalcaemia in
      patients with Graves' disease, there was no difference in the overall frequency
      of biochemical hypocalcaemia, low levels of PTH and/or treatment with calcium and
      vitamin D.

PMID- 22976369
TI  - Kinetics screening of the N-alkylation of organic superbases using a continuous
      flow microfluidic device: basicity versus nucleophilicity.
AB  - We describe here the determination of the alkylation rate of a set of organic
      superbases by iodomethane in DMF using a microfluidic continuous flow reactor.
      Surprisingly, log k(Alkylation) follows the inverse trend of pK(BH+) of the base.
      Mayr's equation allows a more quantitative approach. From a synthetic point of
      view, TMGN and BEMP are demonstrated to be the best choices.

PMID- 22976370
TI  - Transcriptional activation of mouse major satellite regions during neuronal
      differentiation.
AB  - Recent studies have revealed various biological functions for repetitive
      sequences, which make up about half of the human genome. One such sequence, major
      satellites, which are tandem repetitive sequences adjacent to the centromere,
      have been shown to be a kinetochore component that plays a role in the formation
      and function of the pericentric heterochromatin necessary for mitosis. However,
      it is unknown whether these regions also play a role in post-mitotic cells. Here,
      we show that, during neuronal differentiation, the heterochromatin domains that
      include major satellite regions become both enriched with the active histone
      modification lysine-4 trimethylation of histone H3, and more sensitive to
      nuclease, both of which suggest increased activation of this area. Further
      supporting this notion, we also found that transcription from major satellite
      regions is significantly increased during neuronal differentiation both in vitro
      and in vivo. These results together suggest that the structural and
      transcriptional state of major satellite regions changes dramatically during
      neuronal differentiation, implying that this region might play a role in
      differentiating neurons.

PMID- 22976371
TI  - Dynamics of caspase-3 activation and inhibition in embryonic micromasses
      evaluated by a photon-counting chemiluminescence approach.
AB  - Caspases are key enzymatic components of the intracellular apoptotic machinery,
      and their role in mammalian systems is often studied using fluoromethylketone
      (FMK) inhibitors. Despite many advantages of such approach, efficiency of the
      inhibitor and membrane permeability speed are often questioned. This work
      therefore focuses on an exact evaluation of caspase-3 FMK inhibition dynamics in
      camptothecin-induced mesenchymal micromasses. Two parameters of caspase-3 FMK
      inhibitor were investigated: first, the stability of the inhibitory potential in
      the time course of cultivation and, simultaneously, the dynamics of caspase-3 FMK
      inhibition after camptothecin-induced apoptosis peak. A photon-counting
      chemiluminescence approach was applied for quantification of active caspase-3.
      The sensitivity of the photon-counting method allowed for evaluation of active
      caspase-3 concentration in femtogram amounts per cell. The inhibitor penetrated
      the cells within the first minute after its application, and the peak of caspase
      3 started to decline to the blank level after 30 min. The inhibitory effect of
      the FMK inhibitor was unchanged during the entire 48 h of cultivation.

PMID- 22976372
TI  - Synthesis and assembly of a difunctional core POM cluster with two appended POM
      cluster caps.
AB  - A series of nanorod-like organic-inorganic hybrids based on hexamolybdate and
      Anderson-type heteropolyoxomolybdates has been prepared using the well-developed
      DCC protocol. The present work opens a way to flexibly introduce two different
      functional groups to a hexamolybdate ion and explore thoroughly the whole family
      of organoimido derivatives for fabricating novel molecular nanostructures with
      tunable properties.

PMID- 22976373
TI  - Development of T-STAT for early autism screening.
AB  - This study's purpose was to modify the Screening Tool for Autism in Two-Year-Olds
      (STAT) into a Taiwanese version called T-STAT. Study 1 included 15 children with
      Autism and 15 children with Developmental Delay (DD) or language impairment (LI)
      aged between 24 and 35 months. Study 2 had 77 young children with Autism, PDD
      NOS, or DD/LI as a clinical-based validation sample. In Study 1, the signal
      detection procedure found that a cutoff score of 2 would yield high sensitivity
      and specificity in T-STAT. In Study 2, using a score of 2 as a cutoff, the
      agreement between T-STAT risk and ADOS classification was highly acceptable.
      Results were promising as a Level 2 screening tool for Autism for ages two to
      three.

PMID- 22976374
TI  - Brief report: retrospective case series of oxcarbazepine for
      irritability/agitation symptoms in autism spectrum disorder.
AB  - We examined response to oxcarbazepine prescribed for irritability/agitation
      symptoms in a retrospective case series of 30 patients with Autism Spectrum
      Disorder (ASD). The average patient was 12.0 years old (range 5-21) and taking
      two other psychotropic medications (range 0-4). Fourteen patients (47 %) had a
      clinical global impression of improvement score of 'much improved' during
      treatment. Ten patients (33 %) showed an improvement on their clinical global
      impression of severity score. Seven patients (23 %) had a clinically significant
      adverse event or side effect leading to oxcarbazepine discontinuation. Without a
      placebo group, it is not possible to evaluate whether oxcarbazepine provides
      benefit for irritability/agitation symptoms in ASD. The high rate of adverse
      events suggests its use should be accompanied by caution.

PMID- 22976375
TI  - Having been bullied in childhood: relationship to aggressive behaviour in
      adulthood.
AB  - AIMS: Victimization through being bullied in childhood is traditionally
      associated with subsequent internalizing symptoms, but some literature suggests
      otherwise. In this study, we examined a history of being bullied in relationship
      to 21 externalized aggressive behaviours in adulthood. METHODS: Using a cross
      sectional approach and a self-report survey methodology, we examined a history of
      being bullied in childhood in relation to 21 aggression variables in a
      consecutive sample of 342 internal medicine outpatients. RESULTS: In comparison
      with the not bullied, participants who reported having been bullied in childhood
      had a statistically significantly greater overall number of self-reported
      aggressive behaviours. Longer duration of being bullied was statistically
      significantly correlated with a greater number of reported aggressive behaviours.
      With regard to individual behaviours, four were statistically significantly
      associated with being bullied: hitting walls; intentionally breaking things;
      getting into fist fights; and pushing/shoving a partner. CONCLUSIONS: While
      relationships between bullying in childhood and subsequent internalizing symptoms
      have been well established, the present study indicates that bullying in
      childhood is also associated with externalizing/aggressive behaviours in
      adulthood.

PMID- 22976376
TI  - Bad, burdened or ill? Characterizing the spouses of women with schizophrenia.
AB  - BACKGROUND: The husbands of women with schizophrenia have been variously
      characterized in the psychiatric literature as abusive, burdened and ill. The aim
      of this paper is to summarize what has been written about these three
      perspectives. METHOD: The search terms 'schizophrenia', 'mental illness',
      'marriage', 'spouse', 'partner', 'caregiver', 'caregiving', 'burden',
      'assortative mating' and 'domestic abuse' were entered into PubMed and Google
      Scholar. Criteria for inclusion of articles were relevance to the three
      identified themes of abuse, burden and mental illness in husbands of women with
      schizophrenia. The results show considerable variation, some of it cultural, with
      partial evidence for all three characterizations. CONCLUSION: There is a need for
      support and psychoeducation programmes that are specifically designated for
      spouses and that address their special concerns.

PMID- 22976377
TI  - Impact of obesity on perioperative complications and long-term survival of
      patients with gastric cancer.
AB  - BACKGROUND: The prevalence of obesity is increasing in the United States. Obesity
      has been associated with worse surgical outcomes, but its impact on long-term
      outcomes in gastric cancer is unclear. The aim of this study was to evaluate the
      effects of being overweight on surgical and long-term outcomes for patients with
      gastric cancer. METHODS: Patients who underwent curative intent resection for
      gastric carcinoma from 1985 to 2007 were identified from a prospectively
      collected gastric cancer database. Overweight was defined as a body mass index
      (BMI) of 25 kg/m(2) or higher. Clinical outcomes of overweight and nonoverweight
      patients were compared. RESULTS: From the total population of 1,853 patients,
      1,125 (60.7%) were overweight. Overweight patients tended to have more proximal
      tumors and a lower T stage. Accurate complication data were available on a subset
      of patients from 2000 to 2007. A BMI of >=25 was associated with increased
      postoperative complications (47.9 vs. 35.8%, p < 0.001). This was mainly due to
      an increase in the rate of wound infections (8.9 vs. 4.7%, p = 0.02) and
      anastomotic leaks (11.8 vs. 5.4%, p = 0.002). Multivariate logistic regression
      analysis showed that higher BMI, total gastrectomy, and use of neoadjuvant
      chemotherapy were associated with increased wound infection and anastomotic leak.
      Overweight patients were less likely to have adequate lymph node staging (73.3
      vs. 79.2%, p = 0.047). There was no difference in overall survival or disease
      specific survival between the two groups. CONCLUSIONS: Increased BMI is a
      predictor of increased postoperative complications, including anastomotic leak,
      but it is not a predictor of survival in gastric cancer.

PMID- 22976380
TI  - Reactive bonding mediated high mass loading of individualized single-walled
      carbon nanotubes in an elastomeric polymer.
AB  - A reactive chemical bonding strategy was developed for the incorporation of a
      high mass loading of individual single-wall carbon nanotubes (SWCNTs) into an
      elastomeric matrix using a reactive ionic liquid as a linker. This method
      simultaneously prevented the agglomeration of SWCNTs and caused strong
      interfacial bonding, while the electronic properties of the SWCNTs remained
      intact. As a result, the high conductivity of the carbon nanotubes (CNTs) and the
      flexibility of the elastomeric matrix were retained, producing optimum electrical
      and mechanical properties. A composite material with a loading of 20 wt% SWCNTs
      was fabricated with excellent mechanical properties and a high conductivity (9500
      S m(-1)). The method could be used to form transparent thin conductive films that
      could tolerate over 800 bend cycles at a bending angle of 180 degrees  while
      maintaining a constant sheet resistance.

PMID- 22976378
TI  - The rs6983267 SNP is associated with MYC transcription efficiency, which promotes
      progression and worsens prognosis of colorectal cancer.
AB  - BACKGROUND: The oncogenic single nucleotide polymorphism rs6983267, located on
      8q24.21, may affect copy number aberrations and/or expression profiles in
      colorectal cancer (CRC). We investigated the role of this single nucleotide
      polymorphism in the clinical outcome of CRC. METHODS: Array comparative genomic
      hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157
      primary CRC tissues. Expression profiles were analyzed by means of extraction
      expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and
      microsatellite instability were also examined in 107 of the 157 cases. RESULTS:
      aCGH analysis revealed two clusters; more frequent genomic copy number alteration
      (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster
      A. The average CNA was higher in samples containing the major allele (GT/TT) of
      rs6983267 than in those containing the minor allele (GG). Additionally, MYC
      expression was the highest in samples containing the GG allele (n = 18), followed
      by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed
      dominant up-regulation of MYC in samples containing the minor allele. Moreover,
      the presence of the minor allele in a MYC-positive, CNA-negative context
      predicted a poorer prognosis than the presence of the major allele in a MYC
      negative, CNA-positive context in CRC. CONCLUSIONS: The presence of the minor
      allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up
      regulation of MYC transcription. Furthermore, progression of CRC may require
      global CNA in the presence of the major allele and with lack of MYC
      transcription.

PMID- 22976382
TI  - Gold mining impact on riverine heavy metal transport in a sparsely monitored
      region: the upper Lake Baikal Basin case.
AB  - Mining and ore excavation can cause the acidification and heavy metal pollution
      of downstream water systems. It can be difficult to assess the load contributions
      from individual mining areas, which is commonly required for environmental impact
      assessments. In the current study, we quantified the net impact of the
      unmonitored mining activities in the Zaamar Goldfield (Mongolia) on heavy metal
      transport in the downstream Tuul River-Selenga River-Lake Baikal water systems.
      We also noted that the Zaamar site shares the conditions of limited monitoring
      with many rapidly developing regions of the world. The heavy metal concentrations
      and flow data were obtained from historical measurement campaigns, long-term
      monitoring, and a novel field campaign. The results indicate that natural mass
      flows of heavy metals in dissolved form increased by an order of magnitude
      because of mining. Prevailing alkaline conditions in the vicinity of Zaamar can
      limit the dissolution, maintaining the on-site concentrations below health-risk
      based guideline values. However, suspended river concentrations are much higher
      than the dissolved concentrations. The placer gold mining at the Zaamar site has
      increased the total riverine mass flows of Al, As, Cu, Fe, Mn, Pb and Zn by
      44.300, 30.1, 65.7, 47.800, 1.480, 76.0 and 65.0 tonnes per year respectively. We
      suggest that local to regional transformation and enrichment processes in
      combination with suspended sediment transport from numerous existing upstream
      mining areas contribute to high concentrations of dissolved heavy metals in
      downstream parts of the Selenga River, including its delta area at Lake Baikal.
      Furthermore, single hydrological events can increase the suspended load
      concentrations by at least one order of magnitude. Overall, the Selenga River
      Basin, which drains into Lake Baikal, should be recognised as one of the world's
      most impacted areas with regard to heavy metal loads, and it contributes to 1%
      and 3% of the world flux of dissolved Fe and Pb, respectively.

PMID- 22976384
TI  - Virtual-reality balance training with a video-game system improves dynamic
      balance in chronic stroke patients.
AB  - Stroke is one of the most serious healthcare problems and a major cause of
      impairment of cognition and physical functions. Virtual rehabilitation approaches
      to postural control have been used for enhancing functional recovery that may
      lead to a decrease in the risk of falling. In the present study, we investigated
      the effects of virtual reality balance training (VRBT) with a balance board game
      system on balance of chronic stroke patients. Participants were randomly assigned
      to 2 groups: VRBT group (11 subjects including 3 women, 65.26 years old) and
      control group (11 subjects including 5 women, 63.13 years old). Both groups
      participated in a standard rehabilitation program (physical and occupational
      therapy) for 60 min a day, 5 times a week for 6 weeks. In addition, the VRBT
      group participated in VRBT for 30 min a day, 3 times a week for 6 weeks. Static
      balance (postural sway velocity with eyes open or closed) was evaluated with the
      posturography. Dynamic balance was evaluated with the Berg Balance Scale (BBS)
      and Timed Up and Go test (TUG) that measures balance and mobility in dynamic
      balance. There was greater improvement on BBS (4.00 vs. 2.81 scores) and TUG (
      1.33 vs. -0.52 sec) in the VRBT group compared with the control group (P < 0.05),
      but not on static balance in both groups. In conclusion, we demonstrate a
      significant improvement in dynamic balance in chronic stroke patients with VRBT.
      VRBT is feasible and suitable for chronic stroke patients with balance deficit in
      clinical settings.

PMID- 22976385
TI  - Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes
      of influenza virus sialidase 150-loop flexibility.
AB  - Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the
      expanded active site cavity of influenza virus sialidases with an open 150-loop,
      currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4,
      N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for
      inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing
      evidence of the relative 150-loop flexibility of these sialidases. In a complex
      with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150
      cavity while the central ring and the remaining substituents bind the active site
      as seen for the unsubstituted template. This new class of inhibitors, which can
      'trap' the open 150-loop form of the sialidase, should prove useful as probes of
      150-loop flexibility.

PMID- 22976386
TI  - Tobacco smoking, alcohol drinking and risk of oral cavity cancer by subsite:
      results of a French population-based case-control study, the ICARE study.
AB  - The objective was to examine the role of tobacco smoking and alcohol drinking in
      the incidence of oral cavity cancer by subsite in France, a high-incidence area.
      We analysed detailed data on lifelong tobacco smoking and alcohol drinking from
      772 oral cavity cancer cases and 3555 controls included in a population-based
      case-control study, the ICARE study. Tobacco smoking increased the risk of oral
      cavity cancer even for the smaller quantities and durations, whereas alcohol
      drinking increased this risk only in heavy drinkers who were also ever smokers.
      The combined effect of smoking and drinking was greater than multiplicative. The
      floor of the mouth was the subsite that was the most affected by the harmful
      effects of tobacco and alcohol, whereas the gums were less susceptible. The risk
      associated with tobacco and alcohol consumption did not differ between intraoral
      cavity and subsites usually included in the oropharynx (soft palate and base of
      the tongue). Population-attributable risks for oral cavity cancer were 78.6% for
      tobacco smoking, 7.3% for alcohol drinking and 80.7% for tobacco and/or alcohol
      consumption. These results indicate that regular oral check-ups should be
      targeted at smokers and heavy drinkers, and that prevention efforts should be
      focused on smoking cessation.

PMID- 22976387
TI  - Outcomes in cervical screening using various cytology technologies: what's age
      got to do with it?
AB  - Unlike for human papillomavirus screening, little is known about the possible age
      dependent variation in the outcomes of cervical cytology screening. The aim of
      our study was to describe age-related outcomes of five cytological technologies
      in a population-based screening program targeting women aged 23-59 years. All
      cervical cytology from women residing in Copenhagen has been analyzed in the
      laboratory of the Department of Pathology, Hvidovre University Hospital. We
      studied five technology phases: (1) conventional cytology with manual reading,
      (2) conventional cytology with 50% automatically signed out as normal, (3) liquid
      based cytology (LBC) with 50% automatically signed out as normal, (4) LBC with
      25% automatically signed out as normal, and (5) LBC with 25% automatically signed
      out as normal and with 16 preselected areas for attention in manual reading. We
      calculated proportion of samples with atypical squamous cells of undetermined
      significance or worse (>=ASCUS) by age and technology phase. We included 391 140
      samples. The proportion of >=ASCUS increased steadily from 3.8% in phase 1 to
      6.0% in phase 5. This pattern varied considerably across age groups. In women
      aged 23-34 years, the proportion almost doubled, relative proportion 1.96 (95%
      confidence interval: 1.84-2.08). An opposite development was seen in women aged
      45-59 years, relative proportion 0.68 (95% confidence interval: 0.57-0.82).
      Technological upgrading of cytology strongly affected the outcome of cervical
      screening for young women. If corroborated with data from other laboratories,
      these findings call for caution in implementation of new cytology screening
      technologies.

PMID- 22976388
TI  - The influence of physical activity on the profile of immune response cells and
      cytokine synthesis in mice with experimental breast tumors induced by 7,12
      dimethylbenzanthracene.
AB  - This study aims to investigate cytokine synthesis by lymphocytes in the presence
      of mammary tumors and the interaction with physical activity. For this study, we
      used 56 female Balb/c, 8-week-old, virgin mice with a body mass between 20 and 30
      g. The mice were divided into four groups: a no tumor/nontrained control group; a
      no tumor/trained group subjected to physical training of swimming in water (30 +/
      4 degrees C) for 45 min, five times per week for 8 weeks; a tumor/nontrained
      (sedentary) group in which the animals received 7,12-dimethylbenzanthracene
      [(DMBA) 1 mg/ml weekly for 6 weeks)]; and a tumor/trained group in which animals
      were subjected to the aforementioned DMBA tumor induction and swim training
      protocols. After the experimental period, immune cells were collected from spleen
      cell specimens, placed in culture, and stimulated with lipopolysaccharide. The
      presence of cluster of differentiation (CD)3, CD4, and CD8 markers and the
      expression of interferon-gamma, interleukin (IL)-2, IL-4, IL-10, IL-12,
      transforming growth factor beta, and tumor necrosis factor alpha cytokines were
      assessed by flow cytometry and enzyme-linked immunosorbent assay. Physical
      activity increased the quantities of lymphocytes producing interferon gamma, IL
      2, IL-12, and tumor necrosis factor alpha and decreased the quantities of
      lymphocytes and macrophages expressing IL-4, IL-10, and transforming growth
      factor beta. In contrast, tumor induction, in the absence of swim training,
      reduced Th1 cytokine levels while increasing the presence of Th2 cytokines and
      Treg cells. Physical activity promoted reductions in the incidence of tumor
      development and promoted immune system polarization toward an antitumor Th1
      response pattern profile.

PMID- 22976389
TI  - Transgenerational inheritance of induced changes in the epigenetic state of
      chromatin in plants.
AB  - There is growing experimental evidence from both animals and plants that changes
      in the environment can have profound effects on the epigenetic state of chromatin
      in nuclei. The epigenetic state of chromatin and the cell-specific transcription
      profile of genes are mitotically stable and, sometimes, can be transmitted across
      generations. Plants often show stable transgenerational inheritance of induced
      alterations of epigenetic states that are associated with morphologically or
      physiologically distinctive phenotypes. This pattern of inheritance may be due to
      the fact that germ cells produced by terminal differentiation and to the absence
      of appreciable epigenetic reprogramming during the life cycle. Recent advances in
      mass sequencing technology have accelerated the decoding of the epigenomes of
      various tissues and cell types and provided new insights into the dynamics of
      epigenetic changes during the plant life cycle and in response to environmental
      challenges. As plants have a sessile nature, the epigenetic regulation of genes
      and transposable elements in response to environmental stresses might be crucial
      for the generation and inheritance of phenotypic variations in plants in natural
      populations.

PMID- 22976390
TI  - Characterization of Streptococcus criceti insertion sequence ISScr1.
AB  - A novel insertion sequence element of the IS982 family, ISScr1, was previously
      identified in Streptococcus criceti strain E49 as a disrupted paaB gene encoding
      an antigen I/II homologous protein. In this study, we identified two divergent
      inserted regions of ISScr1 in S. criceti E49 by inverse polymerase chain
      reaction, the gene-walking method, and screening of the partial plasmid library.
      Nucleotide sequence analysis indicated the possible explanation that
      transposition generated 8- and 9-bp direct repeat sequences. DNA hybridization
      analysis revealed that an identical hybridization pattern to ISScr1 was observed
      in the four S. criceti strains studied and that at least three copies of ISScr1
      were preserved in S. criceti strains. In addition, we found different
      susceptibility to erythromycin and diverse agglutination properties induced by
      dextran in S. criceti. Furthermore, DNA hybridization analysis showed that no
      ISScr1-like copy was detected in the other 14 strains of oral streptococci
      tested.

PMID- 22976391
TI  - Effect of Ppd-1 on the expression of flowering-time genes in vegetative and
      reproductive growth stages of wheat.
AB  - The photoperiod sensitivity gene Ppd-1 influences the timing of flowering in
      temperate cereals such as wheat and barley. The effect of Ppd-1 on the expression
      of flowering-time genes was assessed by examining the expression levels of the
      vernalization genes VRN1 and VRN3/WFT and of two CONSTANS-like genes, WCO1 and
      TaHd1, during vegetative and reproductive growth stages. Two near-isogenic lines
      (NILs) were used: the first carried a photoperiod-insensitive allele of Ppd-1
      (Ppd-1a-NIL), the other, a photoperiod-sensitive allele (Ppd-1b-NIL). We found
      that the expression pattern of VRN1 was similar in Ppd-1a-NIL and Ppd-1b-NIL
      plants, suggesting that VRN1 is not regulated by Ppd-1. Under long day
      conditions, VRN3/WFT showed similar expression patterns in Ppd-1a-NIL and Ppd-1b
      NIL plants. However, expression differed greatly under short day conditions:
      VRN3/WFT expression was detected in Ppd-1a-NIL plants at the 5-leaf stage when
      they transited from vegetative to reproductive growth; very low expression was
      present in Ppd-1b-NIL throughout all growth stages. Thus, the Ppd-1b allele acts
      to down-regulate VRN3/WFT under short day conditions. WCO1 showed high levels of
      expression at the vegetative stage, which decreased during the phase transition
      and reproductive growth stages in both Ppd-1a-NIL and Ppd-1b-NIL plants under
      short day conditions. By contrast to WCO1, TaHd1 was up-regulated during the
      reproductive stage. The level of TaHd1 expression was much higher in Ppd-1a-NIL
      than the Ppd-1b-NIL plants, suggesting that the Ppd-1b allele down-regulates
      TaHd1 under short day conditions. The present study indicates that down
      regulation of VRN3/WFT together with TaHd1 is the cause of late flowering in the
      Ppd-1b-NIL plants under short day conditions.

PMID- 22976392
TI  - Mutation in OsLMS, a gene encoding a protein with two double-stranded RNA binding
      motifs, causes lesion mimic phenotype and early senescence in rice (Oryza sativa
      L.).
AB  - The rice (Oryza sativa L.) lesion mimic and senescence (lms) EMS-mutant,
      identified in a japonica cultivar Hitomebore, is characterized by a spontaneous
      lesion mimic phenotype during its vegetative growth, an accelerated senescence
      after flowering, and enhanced resistance to rice blast (Magnaporthe oryzae). To
      isolate the OsLMS gene, we crossed the lms mutant to Kasalath (indica), and used
      mutant F(2) plants to initially map the candidate region to about 322-kb on the
      long arm of chromosome 2. Illumina whole-genome re-sequencing of the mutant and
      aligning the reads to Hitomebore reference sequence within the candidate region
      delineated by linkage analysis identified a G to A nucleotide substitution. The
      mutation corresponded to the exon-intron splicing junction of a novel gene that
      encodes a carboxyl-terminal domain (CTD) phosphatase domain and two double
      stranded RNA binding motifs (dsRBM) containing protein. By PCR amplification, we
      confirmed that the mutation causes splicing error that is predicted to introduce
      a premature stop codon. RNA interference (RNAi) transgenic lines with suppressed
      expression of LMS gene exhibited the lesion mimic phenotype, confirming that the
      mutation identified in LMS is responsible for the mutant phenotype. OsLMS shares
      a moderate amino-acid similarity to the Arabidopsis FIERY2/CPL1 gene, which is
      known to control many plant processes such as stress response and development.
      Consistence with this similarity, the lms mutant shows sensitivity to cold stress
      at the early growth stage, suggesting that LMS is a negative regulator of stress
      response in rice.

PMID- 22976393
TI  - A novel composite retrotransposon derived from or generated independently of the
      SVA (SINE/VNTR/Alu) transposon has undergone proliferation in gibbon genomes.
AB  - The superfamily Hominoidea (hominoids) comprises two families: Hominidae
      (hominids) and Hylobatidae (gibbons, also called small apes). The SVA transposon
      is a composite retrotransposon that occurs widely in hominoids and is considered
      to have been generated by stepwise fusions of three genetic elements: SINE-R, a
      variable number of tandem repeat (VNTR) sequence, and Alu. We identified a novel
      transposon whose basic structure is the same as that of SVA, with one prominent
      difference being the presence of part of prostaglandin reductase 2 (PTGR2) in
      place of SINE-R. We designate this composite transposon as PVA and propose two
      possible mechanisms regarding its generation. One is the derivation of PVA from
      SVA: the SINE-R region of SVA was replaced with a PTGR2 fragment by template
      switching. The other is the formation of PVA independently of SVA: a PTGR2
      fragment was fused to an evolutionary intermediate comprising the VNTR and Alu
      regions. The nucleotide sequence of the junction between the VNTR and PTGR2
      regions supports the second hypothesis. We identified PVA in the white-cheeked
      gibbon Nomascus leucogenys by analysis of genome sequence databases, and
      subsequent experimental analysis revealed its presence in all four gibbon genera.
      The white-cheeked gibbon harbors at least 93 PVA copies in its haploid genome.
      Another SVA-like composite transposon carrying parts of the LINE1 and Alu
      transposons in place of SINE-R, designated as LAVA, has recently been reported.
      The significance of the discovery of PVA is that its substituted fragment
      originates not from a transposon but from a single-copy gene. PVA should provide
      additional insights into the transposition mechanism of this type of composite
      transposon; the transposition activity is conferred even if the substituted
      fragment is not related to a transposon.

PMID- 22976394
TI  - Association of single nucleotide polymorphisms (SNPs) of PADI4 gene with
      rheumatoid arthritis (RA) in Indian population.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting
      ~ 1% of the population worldwide. The genome wide association studies on RA
      patients revealed linkage with 1p36 locus containing peptidyl arginine deiminase
      4 (PADI4) genes. Case-control association studies and mRNA stability assays
      reported the association of PADI4 gene with RA in Korean and Japanese
      populations. However, such association was not found in Spanish population.
      Differences in the association of PADI4 with RA in different populations prompted
      the present study in Indian population. Anti-CCP antibodies, RF antibody, disease
      activity scores at 28 joints (DAS28) and mutations in three exons of PADI4 were
      investigated in RA patients and control group. Among the patients anti-CCP
      antibody levels were found to be associated with high DAS28 values (r = 0.4526, P
      < 0.0001). Polymorphism in exon-4 (padi4_104, [rs1748033]) of PADI4 showed
      significant association of 'C' allele with RA in the study population (P =
      0.0008). Polymorphism in exon-3 (padi4_92, [rs874881]) also exhibited moderate
      association with the disease (P = 0.075). However, no association of the disease
      was found with the SNPs padi4_89 [rs11203366] and padi4_90 [rs11203367] in exon-2
      of PADI4.

PMID- 22976395
TI  - A bioinformatics strategy for detecting the complexity of Chronic Obstructive
      Pulmonary Disease in Northern Chinese Han Population.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a complex human disease which is
      driven not only by genetic factors, but also by various environmental variables,
      such as gender, age and smoking. Therefore, there is a demand for investigating
      the complexity among various risk factors involved in COPD. In this study, 44
      tagging SNPs from EPHX1, GSTP1, SERPINE2 and TGFB1 were selected and genotyped in
      310 COPD cases and 203 controls, all of which belong to the Han from North China.
      We integrated functional prediction algorithms of nonsynonymous SNPs (nsSNPs)
      into Bayesian network to explore the complex regulatory relationships among
      disease traits and various risk factors. The results showed that three basic
      variables (age, sex and smoking) were risk factors of COPD-related trait and
      phenotype. Besides these environmental risk factors, deleterious nsSNPs were
      found to perform better than those of significant synonymous SNPs when used as
      variables to make risk prediction of disease outcome. This study provides further
      evidences for detecting the complexity of COPD in Northern Chinese Han
      Population.

PMID- 22976397
TI  - The relative contributions of radial and laminar optic flow to the perception of
      linear self-motion.
AB  - When illusory self-motion is induced in a stationary observer by optic flow, the
      perceived distance traveled is generally overestimated relative to the distance
      of a remembered target (Redlick, Harris, & Jenkin, 2001): subjects feel they have
      gone further than the simulated distance and indicate that they have arrived at a
      target's previously seen location too early. In this article we assess how the
      radial and laminar components of translational optic flow contribute to the
      perceived distance traveled. Subjects monocularly viewed a target presented in a
      virtual hallway wallpapered with stripes that periodically changed color to
      prevent tracking. The target was then extinguished and the visible area of the
      hallway shrunk to an oval region 40 degrees  (h) * 24 degrees  (v). Subjects
      either continued to look centrally or shifted their gaze eccentrically, thus
      varying the relative amounts of radial and laminar flow visible. They were then
      presented with visual motion compatible with moving down the hallway toward the
      target and pressed a button when they perceived that they had reached the
      target's remembered position. Data were modeled by the output of a leaky spatial
      integrator (Lappe, Jenkin, & Harris, 2007). The sensory gain varied
      systematically with viewing eccentricity while the leak constant was independent
      of viewing eccentricity. Results were modeled as the linear sum of separate
      mechanisms sensitive to radial and laminar optic flow. Results are compatible
      with independent channels for processing the radial and laminar flow components
      of optic flow that add linearly to produce large but predictable errors in
      perceived distance traveled.

PMID- 22976399
TI  - The effect of variability in other objects' sizes on the extent to which people
      rely on retinal image size as a cue for judging distance.
AB  - Retinal image size can be used to judge objects' distances because for any object
      one can assume that some sizes are more likely than others. It has been shown
      that an increased variability in the size of otherwise identical target objects
      over trials reduces the weight given to retinal image size as a distance cue.
      Here, we examined whether an increased variability in the size of objects of a
      different color, orientation, or shape reduces the weight given to retinal image
      size when judging distance. Subjects had to indicate the 3D position of a
      simulated target object. Retinal image size was given significantly less weight
      as a cue for judging the target cube's distance when differently colored and
      differently oriented target objects appeared in many simulated sizes but not when
      differently shaped objects had many simulated sizes. We also examined whether
      increasing the variability in the size of cubes in the surroundings reduces the
      weight given to retinal image size when judging distance. It does not. We
      conclude that variability in surrounding or dissimilar objects' sizes has a
      negligible influence on the extent to which people rely on retinal image size as
      a cue for judging distance.

PMID- 22976400
TI  - The ACA decision: law and philosophy.

PMID- 22976401
TI  - Are you feeling empowered yet?

PMID- 22976402
TI  - The many vs. the few.

PMID- 22976403
TI  - Abortion bans premised on fetal pain capacity.

PMID- 22976404
TI  - The Affordable Care Act survives, for now.

PMID- 22976405
TI  - A mutual aid society?

PMID- 22976406
TI  - Justice Roberts's health care stewardship.

PMID- 22976407
TI  - Saved from themselves.

PMID- 22976408
TI  - Lessons to improve the efficiency and equity of health reform.

PMID- 22976409
TI  - The carelessness of affordable care.

PMID- 22976410
TI  - How many Justices does it take to change the U.S. health system? Only one, but it
      has to want to change.

PMID- 22976411
TI  - Personalized genomic medicine and the rhetoric of empowerment.

PMID- 22976412
TI  - Maintaining trust in newborn screening: compliance and informed consent in the
      Netherlands.

PMID- 22976414
TI  - Another roadblock to including women in research.

PMID- 22976416
TI  - The development and testing of a survey to measure patient and family experiences
      with injury care.
AB  - BACKGROUND: To deliver patient-centered trauma care, we must capture patient and
      family experiences with the services they receive. We developed and pilot tested
      a survey to measure patient and family experiences with major injury care.
      METHODS: We conducted a structured literature review and focus groups to generate
      survey items. We pilot tested the survey at a Level I trauma center and assessed
      feasibility of implementation and construct validity with Spearman's correlation
      coefficients. Open ended questions were qualitatively analyzed to explore whether
      responses corroborated survey content. RESULTS: We developed a survey with two
      parts: acute care component (46 items) and post-acute care component (27 items)
      with nine domains. We offered the survey (acute care component offered before
      hospital discharge, post-acute care component offered 1-7 months after discharge)
      to 170 patients/families, of whom 134 (79%) responded. Patients were primarily
      male (73%) with major injuries (median Injury Severity Score, 18; interquartile
      range, 16-25). Overall, respondents for both the acute care and post-acute care
      components of the survey reported being completely (47% vs. 26%), very (37% vs.
      38%), or mostly (16% vs. 21%) satisfied with their injury care, whereas a
      minority reported being slightly (0% vs. 9%) or very (0% vs. 6%) dissatisfied (p
      = 0.002 Fischer's exact test). Most survey items were significantly correlated
      with overall satisfaction (46 of 60 items). Almost all qualitatively identified
      themes matched survey domains, adding support to the survey content. CONCLUSION:
      This pilot study demonstrates the feasibility of implementing a survey to capture
      patient and family experiences associated with major injury care and provides
      preliminary evidence of the instrument's content and construct validity. LEVEL OF
      EVIDENCE: Epidemiologic study, level III.

PMID- 22976417
TI  - Therapeutic effects of inhaling aerosolized surfactant alone or with
      dexamethasone generated by a novel noninvasive apparatus on acute lung injury in
      rats.
AB  - BACKGROUND: Pulmonary surfactant (PS) administration has been attempted for the
      treatment of adults with acute lung injury (ALI)/adult respiratory distress
      syndrome. Aerosolized surfactants inhaled by spontaneous breathing may be an
      effective method of surfactant-based therapies. Using a noninvasive apparatus, we
      evaluated the therapeutic effects of aerosolized PS alone or together with
      dexamethasone (Dex) on a rat model of ALI. METHODS: Severe ALI was induced by
      intravenous injection of 20% oleic acid (0.2 mL/kg) into adult Sprague-Dawley
      rats. Animals were divided into eight groups: sham (n = 10); model (injury only,
      n = 10); normal saline (NS) aerosol driven by compressed air (air-NS, n = 13); PS
      aerosol driven by compressed air (air-PS, n = 13); NS aerosol driven by O2 (O2
      NS, n = 13); PS aerosol driven by O2 (O2-PS, n = 13); Dex aerosol driven by O2
      (O2-Dex, n = 13); and PS and Dex aerosol driven by O2 (O2-PS-Dex, n = 13). Blood
      gases, breathing rate, lung index, total protein, and proinflammatory cytokines
      (tumor necrosis factor-alpha, interleukin 1beta, interleukin 6) in the
      bronchoalveolar lavage fluid (BALF), and lung histology were examined. RESULTS:
      Animals treated with air-PS for 20 minutes had significantly improved lung
      function, reduced pulmonary edema, decreased concentration of total protein and
      proinflammatory cytokines in BALF, ameliorated lung injury, and improved animal
      survival. In the O2-PS group, the breathing rates and lung injury scores were
      significantly lower than that of the air-PS group. In the O2-PS-Dex group, lung
      edema, total protein, and inflammatory cytokines in BALF were significantly
      reduced in comparison with the O2-PS group. CONCLUSION: Inhalation of aerosolized
      PS generated by the noninvasive apparatus could significantly reduce lung injury,
      while using oxygen line available in the clinical wards to generate PS aerosol is
      more convenient and adds further benefits. This method can also be used to
      deliver Dex and other therapeutic agents to ameliorate lung injury.

PMID- 22976418
TI  - Molecular mechanism of sustained inflation in acute respiratory distress
      syndrome.
AB  - BACKGROUND: The aim of this study was to investigate the effect and the potential
      molecular mechanism of sustained inflation (SI) recruitment maneuvers in acute
      respiratory distress syndrome (ARDS) in beagle dog following endotracheal
      suctioning. METHODS: ARDS was induced in 24 beagle dogs with oleic acid. They had
      mechanical ventilation support. They were randomized into four groups after the
      establishment of the ARDS model: non-SI-open group where no SI was applied in
      beagle dogs with ARDS following open endotracheal suctioning; non-SI-closed group
      where no SI was applied in beagle dogs with ARDS following closed endotracheal
      suctioning; SI-open group where SI was applied in beagle dogs with ARDS following
      open endotracheal suctioning; and SI-closed group where SI was applied in beagle
      dogs with ARDS following closed endotracheal suctioning. Oxygenation, indexes of
      respiratory mechanics, and hemodynamic indexes were serially measured during the
      procedure. The serum protein level, or the messenger RNA in the heart and lung,
      of inflammation-related cytokines was investigated. RESULTS: SI in ARDS improved
      oxygenation, lung compliance, and airway resistance but had no significant effect
      in the hemodynamic indexes. At molecular level, SI in ARDS neutralized the
      increases of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin
      1beta [IL-1beta], and IL-6), and anti-inflammatory cytokine (IL-10) in the serum.
      Furthermore, SI in ARDS increased aquaporin 1 and aquaporin 5 messenger RNA in
      the lung tissue, and decreased IL-6 messenger RNA in the lung and heart tissue.
      CONCLUSION: SI in ARDS could improve oxygenation, lung compliance, and airway
      resistance, which was related to the improved degree of inflammation and better
      maintained aquaporins.

PMID- 22976419
TI  - The misapplication of the term spinal cord injury without radiographic
      abnormality (SCIWORA) in adults.
AB  - BACKGROUND: Spinal cord injury without radiographic abnormality (SCIWORA) is
      generally considered a disease of children; however, it is commonly used when
      referring to adults who have spinal cord injury without computed tomography
      evidence of trauma (SCIWOCTET). The purpose of this study was to describe
      characteristics of patients with both adult and pediatric cervical SCIWOCTET
      admitted to hospitals in our region. METHODS: A retrospective review of all
      patients admitted to our two ACS-verified trauma centers with cervical spinal
      cord injury from January 2005 to December 2009 was performed. All patients with
      vertebral or ligamentous injury identified on computed tomographic (CT) scan of
      the cervical spine were excluded. Data gathered on the remaining patients
      included demographics, injury mechanism, Injury Severity Score, neurologic level
      and severity of spinal cord injury, magnetic resonance imaging results, and
      mortality rates. RESULTS: During the 5-year period of this study, 11,644 adult
      patients and 3,458 pediatric trauma patients were admitted. Of these, 313
      patients were thought to have cervical spinal cord injury based on International
      Classification of Diseases, Ninth Revision (ICD-9) codes, 279 (89.1%) were
      excluded due to injury noted on CT cervical spine, and 9 were excluded as they
      were found to not truly have cervical spinal cord injury after review of the
      medical record. The remaining 25 patients were identified as having cervical
      SCIWOCTET. Twenty-three patients (92%) were male. The patient ages ranged from 10
      to 83 years with a median age of 56 years. The mean Injury Severity Score was
      22.6. Sixty-eight percent had a mechanism of fall. Degenerative changes were
      found on the CT scan of the cervical spine in 96% of all patients and in all 24
      adult patients. There was only one pediatric patient with SCIWORA, a 10-year-old
      boy who had a normal CT scan of the cervical spine but had a persistent
      neurologic deficit. CONCLUSION: SCIWOCTET is mainly a disease of adults, and its
      subset SCIWORA, a disease of children, is much less common. Adults with this
      disease have CT scans showing canal stenosis and significant degenerative changes
      in the cervical spine; thus, it is not accurate to state that they have SCIWORA.
      The characteristics of this patient population are important as SCIWOCTET is the
      concern when clearing the cervical spines of trauma patients with a CT scan of
      the cervical spine negative for injury. LEVEL OF EVIDENCE: Epidemiologic study,
      level III.

PMID- 22976420
TI  - The immune response to surgery and trauma:  Implications for treatment.
AB  - BACKGROUND: Infection after surgery and trauma is a major cause of increased
      morbidity, mortality, and cost. Alterations of the hosts immune system following
      these insults is believed to be responsible for the increased risk of infection.
      The hosts' immune response to tissue injury is widely believed to follow a
      bimodal response, with the systemic inflammatory response syndrome (SIRS)
      followed by the compensated anti-inflammatory response syndrome (CARS). Recent
      data, however, suggests that his paradigm may not be correct. METHODS: We
      reviewed the literature to describe the immunological changes following surgery
      and trauma and possible therapeutic interventions to limit this process. RESULTS:
      Physical injury related to trauma and surgery increase the expression of T-helper
      2 (Th2) lymphocytes which cause impaired cell mediated immunity (CMI). Activation
      of the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system (SAS)
      with the release of cortisol and catecholamines appear to be responsible for
      altering the Th1/Th2 balance. Decreased expression and signalling of interleukin
      12 (IL-12) and increased expression of T regulatory cells (Tregs) appear to play
      a central role in mediating this immune depression. Furthermore, Th2 cytokines
      increase the expression of arginase-1 (ARG1) in myeloid-derived suppressor cells
      (MDSC's) causing an arginine deficient state, which further impairs lymphocyte
      function. Immunomodulating diets (IMDs) containing supplemental arginine and
      omega-3 fatty acids have been demonstrated to restore the Th1/Th2 balance after
      surgical trauma and to reduce the risk of infectious complications. beta
      adrenergic receptor blockage reverses the Th-1 to Th2 shift and preliminary data
      suggests that such therapy may be beneficial. CONCLUSION: Tissue injury following
      surgery and trauma results in depressed CMI leading to an increased risk of
      infections. The peri-operative use of IMDs appear to reverse this
      immunosuppression and decrease the risk of postoperative complications. While
      beta-adrenoreceptor blockage may be beneficial in these patients, particularly
      when combined with a IMD, additional research is required.

PMID- 22976421
TI  - New anticoagulants:  A concise review.
AB  - During the last 2 years, two new oral anticoagulants, dabigatran and rivaroxaban,
      have been approved in the United States. Phase II and Phase III clinical trials
      of dabigatran, rivaroxaban, and apixaban are summarized. Approach to
      perioperative management depends on the half-life of the medication, risk of
      surgical bleeding, and the patient's renal function. No reversal agent is
      available for any of the new oral anticoagulants. Management of bleeding patients
      is based on local measures and consideration of antifibrinolytic therapy and
      activated factor VII or prothrombin complex concentrate infusion based on healthy
      volunteer and animal studies. The new oral anticoagulants provide additional
      options to prevent venous thromboembolism in patients after orthopedic surgery or
      stroke in patients with atrial fibrillation but present unique challenges
      compared to warfarin.

PMID- 22976423
TI  - Inhibiting tryptase after ischemia limits small intestinal ischemia-reperfusion
      injury through protease-activated receptor 2 in rats.
AB  - BACKGROUND: Mast cell activation plays a key role in the process of small
      intestinal ischemia-reperfusion (IIR) injury; however, the precise role of
      tryptase released from mast cell on IIR injury remains poorly understood. The aim
      of this study was to determine the protective role against IIR injury by using
      tryptase inhibitor protamine after ischemia and to explore the underlying
      mechanism. METHODS: Adult Sprague-Dawley rats were randomized into sham-operated
      group (S), sole IIR group (IIR) in which rats were subjected to 75-minute
      superior mesenteric artery occlusion followed by 4-hour reperfusion, or IIR being
      respectively treated with mast cell stabilizer cromolyn sodium (CS group), with
      the mast cell degranulator compound 48/80 (CP group), or with protamine (P
      group). The previously mentioned agents were, respectively, administered
      intravenously 5 minutes before reperfusion. The intestine tissue was obtained for
      histologic assessment and assays for protein expressions of tryptase and mast
      cell protease 7 and protease-activated receptor 2 (PAR-2). The intestine mast
      cell number and levels of tumor necrosis factor kappa and interleukin 8 were
      quantified. RESULTS: IIR resulted in intestinal injury evidenced as significant
      increases in Chiu's scores, accompanied with concomitant increases of mast cell
      counts and intestinal tryptase and mast cell protease 7 protein expressions. IIR
      also increased intestinal PAR-2 expressions, tumor necrosis factor kappa, and
      interleukin 8 levels. Cromolyn sodium and protamine significantly reduced the
      responses to IIR injury while compound 48/80 further aggravated the previously
      mentioned biochemical changes. CONCLUSION: Tryptase releasing from mast cell
      activation participates in IIR injury through PAR-2, and inhibiting tryptase
      after ischemia provides promising benefits in limiting IIR injury.

PMID- 22976424
TI  - Unintentional firearm death across the urban-rural landscape in the United
      States.
AB  - BACKGROUND: Unintentional injuries are one of the leading causes of death in the
      United States. Many of these injuries are preventable, and unintentional firearm
      injuries, in particular, may be responsive to prevention efforts. We investigated
      the relationship between unintentional firearm death and urbanicity among adults.
      METHODS: This study was a retrospective analysis of national death certificate
      data. Unintentional adult firearm deaths in the United States from 1999 to 2006
      were identified using the Multiple Cause of Death Data files from the National
      Center for Health Statistics. Decedents were assigned to a county of death and
      classified along an urban-rural continuum defined by population density and
      proximity to metropolitan areas. Total unintentional firearm death rates by
      county were analyzed in adjusted analyses using negative binomial regression.
      RESULTS: A total of 4,595 unintentional firearm injury deaths of adults occurred
      in the United States during the study period (a mean of 574.4 per year). Adjusted
      rates of unintentional firearm death showed increases from urban to rural
      counties. Americans in the most rural counties were significantly more likely to
      die of unintentional firearm deaths than those in the most urban counties
      (relative rate, 2.16; 95% confidence interval, 1.44-3.21, p = 0.002). CONCLUSION:
      Rates of unintentional firearm death are significantly higher in rural counties
      than in urban counties. Prevention strategies should be tailored to account for
      both geographic location and manner of firearm injury. LEVEL OF EVIDENCE:
      Epidemiologic study, level III.

PMID- 22976425
TI  - Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem
      cells in traumatic brain injury rats.
AB  - BACKGROUND: The aim of the present study was to investigate whether secretome
      obtained from normoxia-preconditioned human mesenchymal stem cells causes
      attenuation of traumatic brain injury (TBI), induced by fluid percussion injury.
      METHODS: Anaesthetized male Sprague-Dawley rats, immediately after the onset of
      fluid percussion TBI, were divided into two major groups and given the vehicle
      solution (1 mL) or secretome (500 ug) intravenously. Another group of rats was
      used as sham-operated controls. The functional outcome such as motor (maximum
      grasp angle) was evaluated by an inclined plane test. Cellular infarction volume
      was calculated by triphenyltetrazolium chloride staining. Neuronal loss,
      apoptosis, and neurotrophic factor such as vascular epithelial growth factor
      (VEGF) expression in the cortex were measured by immunofluorescence staining. All
      the parameters were assessed on Day 3 after injury. RESULTS: Compared with those
      of the sham-operated controls, the motor deficits and cerebral infarction of rats
      after TBI were significantly attenuated by secretome therapy. The TBI-induced
      neuronal loss and apoptosis were also significantly reduced by secretome therapy.
      Furthermore, VEGF-positive cells in the ischemic cortex after TBI were further
      significantly increased by secretome therapy. CONCLUSION: Our results demonstrate
      that intravenous injection of secretome from normoxia-preconditioned human
      mesenchymal stem cells may ameliorate TBI-induced rats by reducing neuronal cell
      loss and apoptosis and promoting VEGF production, resulting in functional outcome
      improvement. We also recommend that secretome from normoxia-preconditioned human
      mesenchymal stem cells could be a promising treatment strategy for traumatic
      brain injury.

PMID- 22976426
TI  - Degradation of fluorobenzene and its central metabolites 3-fluorocatechol and 2
      fluoromuconate by Burkholderia fungorum FLU100.
AB  - A halobenzene-degrading bacterium, Burkholderia fungorum FLU100 (DSM 23736), was
      isolated due to its outstanding trait to degrade fluorobenzene. Besides
      fluorobenzene, it utilizes, even in random mixtures, chlorobenzene, bromobenzene,
      iodobenzene, benzene, and toluene as sole sources of carbon and energy. FLU100
      mineralizes mono-halogenated benzenes almost stoichiometrically (according to
      halide balance); after a lag phase, it also degrades 3-fluorophenol and 3
      chlorophenol completely. The FLU100-derived transposon Tn5-mutant FLU100-P14R22
      revealed 3-halocatechol to be a central metabolite of this new halobenzene
      degradation pathway. In FLU100, halocatechols are-as expected-strictly subject to
      ortho-cleavage of the catechol ring, with meta-cleavage never been observed. The
      strain is able to completely mineralize 3-fluorocatechol, the principal
      catecholic metabolite being nearly exclusively formed from fluorobenzene. The
      temporarily excreted 2-fluoromuconate formed thereof in turn is subsequently
      metabolized completely. This important finding falsifies the customary opinion of
      the persistence of 2-fluoromuconate valid up to now. The degradation of 4
      fluorocatechol, however, being a very minor intermediate in FLU100, is
      substantially slower and incomplete and leads to the accumulation of
      uncharacterized derivatives of muconic acid and muconolactone in the medium. This
      branch therefore does not seem to be productive. To our knowledge, this
      represents the first example of the complete metabolism of 3-fluorocatechol via 2
      fluoromuconate, a metabolite hitherto described as a dead-end metabolite in
      fluoroaromatic degradation.

PMID- 22976428
TI  - Regional anesthesia in Marfan syndrome, not all dural ectasias are the same: a
      report of two cases.
AB  - BACKGROUND: The anesthetic management of women with Marfan syndrome and dural
      ectasia undergoing Cesarean delivery remains controversial. We present two cases
      of patients with Marfan syndrome and dural ectasia where neuraxial anesthesia was
      used successfully. CASE 1: A 31-yr-old G1P0 female with Marfan syndrome presented
      for elective Cesarean delivery at 35(3/7) weeks' gestation. The magnetic
      resonance imaging of her spine revealed significant dural ectasia in the
      lumbosacral area with a mean lumbar dural sac area of 4.71 cm(2). Intrathecal
      administration of 0.75% hyperbaric bupivacaine 9 mg produced only limited
      perineal analgesia. The epidural catheter was titrated, and 0.5% bupivacaine 150
      mg were required to achieve a T4 sensory level. CASE 2: A 34-yr-old G1P0 female
      with Marfan syndrome presented for elective Cesarean delivery at 37 weeks'
      gestation. The intrathecal administration of 0.75% hyperbaric bupivacaine 13.5 mg
      produced a T5 sensory level. Magnetic resonance imaging of her spine prior to
      discharge confirmed the diagnosis of moderate dural ectasia with a mean lumbar
      dural sac area of 3.61 cm(2). DISCUSSION: The two patients described in this
      report responded differently to spinal anesthesia, most likely based on the
      severity of their dural ectasia. Although preoperative magnetic resonance imaging
      may help to identify patients at risk for a failed spinal, we suggest considering
      a combined spinal-epidural technique in cases of dural ectasia.

PMID- 22976427
TI  - Assessment and treatment of repeated implantation failure (RIF).
AB  - Repeated implantation failure (RIF) is determined when embryos of good quality
      fail to implant following several in vitro fertilization (IVF) treatment cycles.
      Implantation failure is related to either maternal factors or embryonic causes.
      Maternal factors include uterine anatomic abnormalities, thrombophilia, non
      receptive endometrium and immunological factors. Failure of implantation due to
      embryonic causes is associated with either genetic abnormalities or other factors
      intrinsic to the embryo that impair its ability to develop in utero, to hatch and
      to implant. New methods of time-lapse imaging of embryos and assessment of their
      metabolic functions may improve selection of embryos for transfer, and subsequent
      outcomes for IVF patients, as well as for those diagnosed with RIF. This review
      discusses the various causes associated with RIF and addresses appropriate
      treatments.

PMID- 22976429
TI  - [Psychological distress measured using the Kessler scale (K6) predicts long-term
      postoperative pain after wrist surgery].

PMID- 22976430
TI  - Gastric bypass increases ethanol and water consumption in diet-induced obese
      rats.
AB  - BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for
      morbid obesity. Increased alcohol abuse after RYGB resulted in recommendations to
      exclude patients with alcohol abuse histories from RYGB. The purpose of our study
      was to examine the effects of a RYGB on ethanol intake in diet-induced obese rats
      (high-fat diet). METHODS: The animals underwent RYGB and were habituated along
      with their sham-operated obese controls and with lean rats to increasing
      concentrations of ethanol in a two-bottle choice paradigm. RESULTS: RYGB rats'
      daily consumption of ethanol averaged 2 g/kg at 2% habituation and 3.8 g/kg at 4%
      habituation, twice as much as sham-operated obese controls and 50% more than
      normal-diet lean controls. Obese controls drank on average 1 g/kg of ethanol (2
      and 4%), significantly less (50%) than lean controls did. RYGB rats when given
      higher ethanol concentrations (6 and 8%) or no ethanol drank significantly more
      water than lean and obese controls did (66 and 100%, respectively), and their
      enhanced total fluid intake was associated with increased food intake, which was
      significantly higher than in lean (66% more calories; food + alcohol) and obese
      controls (44% more calories). The lower alcohol intake in the obese controls than
      in the lean rats suggests that obesity may interfere with alcohol's rewarding
      effects and RYGB may remove this protective effect. CONCLUSIONS: The overall
      enhancement of consummatory behaviors (both ethanol and water) suggests that RYGB
      may facilitate alcohol consumption, which in vulnerable individuals could lead to
      abuse and addiction.

PMID- 22976431
TI  - Evaluation of a porcine whole-limb heterotopic autotransplantation model.
AB  - BACKGROUND: Recently performed vascularized composite tissue allotransplantations
      (CTAs) stimulate the ongoing research in the area of whole-limb transplantation.
      A reliable in vivo animal model is required for investigations in vascularized
      whole-limb CTA. The model should allow in vivo assessment in whole-limb
      preservation, allograft and xenograft response, and host immunomodulation. The
      goal of this study is to describe and evaluate the in vivo feasibility and
      reproducibility of a whole-limb porcine model as a basis for future research in
      this field. MATERIALS AND METHODS: In seven large white pigs, one forelimb was
      amputated under anesthesia and autotransplanted heterotopically with an arc of
      rotation of 180 degrees  and partially placed in a subcutaneous pocket. Clinical
      parameters were monitored and muscle biopsies were analyzed using ultrastructural
      morphological assessment of mitochondria quality after an observation period of 7
      days. RESULTS: All animals could fully mobilize postoperatively without
      restrictions. At sacrifice, the anastomosed pedicle vessels of the limb were
      patent in six animals. In one pig, venous thrombosis could be observed. Muscle
      response was triggered following direct electrostimulation in six replanted
      limbs. The replanted extremities gained 12.97% weight within 7 days
      postreplantation compared with the amputation baseline values (P = 0.464 while
      maintaining normal compartment pressures at sacrifice (8.25 +/- 5.31 cmH(2)O, P =
      0.60). The ultrastructural evaluation of mitochondria morphology revealed intact
      mitochondria without signs of ischemia/reperfusion damage. CONCLUSION: This
      porcine model proved feasible, reliable, and reproducible for whole-limb
      autotransplantation. It presents significant potential in future preclinical
      research of whole-limb CTA transplantation.

PMID- 22976432
TI  - Highly ordered periodic mesoporous organosilica nanoparticles with controllable
      pore structures.
AB  - A general synthetic procedure for highly ordered and well-dispersed periodic
      mesoporous organosilica (PMO) nanoparticles is reported based on a single
      cationic surfactant cetyltrimethylammonium bromide (CTAB) and simple silica
      sources with organic bridging groups via an ammonia-catalyzed sol-gel reaction.
      By changing the bridging group in the silica sources, the pore structures of the
      as-made particles with three-dimensional hexagonal (P6(3)/mmc), cubic (Pm3n), two
      dimensional hexagonal (P6mm), and wormlike structure were evidenced by powder X
      ray diffraction analysis (XRD) and transmission electron microscopy (TEM). The
      size range of the nanoparticles can be adjusted from 30 nm to 500 nm by variation
      of the ammonia concentration or the co-solvent content of the reaction medium.
      The PMO nanoparticles with high concentration of organic groups in the framework
      offered good thermal stability, good dispersion in low polarity solvent and high
      adsorption of small hydrophobic molecules. Finally, the dye functionalized PMO
      nanoparticles show low cytotoxicity and excellent cell permeability, which offers
      great potential for biomedical applications.

PMID- 22976434
TI  - Immunotherapy: Isolation of T(CM) cells for tumour immunotherapy.

PMID- 22976433
TI  - Evolutionary conflicts between viruses and restriction factors shape immunity.
AB  - Host restriction factors are potent, widely expressed intracellular blocks to
      viral replication that are an important component of the innate immune response
      to viral infection. However, viruses have evolved mechanisms that antagonize
      restriction factors. Through evolutionary pressure for both host survival and
      virus replication, an evolutionary 'arms race' has developed that drives
      continuous rounds of selection for beneficial mutations in the genes encoding
      restriction factors and their viral antagonists. Because viruses can evolve
      faster than their hosts, the innate immune system of modern-day vertebrates is
      for the most part optimized to defend against ancient viruses, rather than newer
      viral threats. Thus, the evolutionary history of restriction factors might, in
      part, explain why humans are susceptible or resistant to the viruses present in
      the modern world.

PMID- 22976435
TI  - Autoimmunity: The lung takes over CNS traffic control.

PMID- 22976436
TI  - T cell responses: Dancing in the dark.

PMID- 22976437
TI  - Highly effective alkaline earth catalysts for the sterically governed
      hydrophosphonylation of aldehydes and nonactivated ketones.

PMID- 22976438
TI  - Haematology and blood chemistry changes in mice treated with terbuthylazine and
      its formulation Radazin TZ-50.
AB  - TBA is an herbicide in general low acute toxicity and placed into a third
      category of toxicity. The aim of this study was to determine the effect of TBA
      and its formulation Radazin TZ-50 in doses of ADI values and 1/100 LD 50 on
      haematological and biochemical blood parameters in mice. The number of leukocytes
      was significantly decreased (p < 0.05) in all treated groups compared to non
      treated mice (8.81 +/- 3.23 * 10(9)/L). The lowest value 3.90 +/- 0.74 * 10(9)/L
      was observed in group treated with TBA (1/100 LD 50) followed by TBA (ADI) 4.49
      +/- 0.98 * 10(9)/L, Radazin TZ-50 (1/100 LD 50) 4.67 +/- 1.24 * 10(9)/L and
      Radazin TZ-50 (ADI) 4.73 +/- 1.15 * 10(9)/L. The values of the enzyme AST was
      increased from 190.00 +/- 26.46-270.00 +/- 147.30 U/L in serum of all treated
      groups as compared to non-treated mice (110.00 +/- 20.00). LDH values showed
      significant increase (3236.67 +/- 56.86-4054.33.5 +/- 837.16 U/L) as compared to
      non-treated mice (1010.00 +/- 222.71 U/L). Total protein value was significantly
      (p < 0.05) increased in TBA 1/100 LD50 (63.00 +/- 7.48 g/L) and Radazin TZ-50
      1/100 LD50 (60.00 +/- 2.00 g/L) compared to non-treated mice 52.00 +/- 4.00 g/L.
      Increased serum concentrations of urea and creatinine obtained in mice treated
      with TBA and Radazin TZ-50 indicates a greater degree of dysfunction of the
      nephron. TBA and its formulation of Radazin TZ-50 in applied doses demonstrate
      changes in the number of leukocytes and limited hepatotoxic effects.

PMID- 22976439
TI  - Toxicity of ammonia nitrogen to ciliated protozoa Stentor coeruleus and Coleps
      hirtus isolated from activated sludge of wastewater treatment plants.
AB  - We assessed the toxicity of ammonia ions to Stentor coeruleus and Coleps hirtus
      (Protozoa) isolated from activated sludge taken from two municipal wastewater
      treatment plants in southern Poland. Stentor coeruleus is a rarely occurring
      species in activated sludge, unlike the widespread Coleps hirtus. The mean LC50
      values (concentration causing 50 % mortality) calculated for the 24 h tests
      differed hugely between the tested species: 43.03 mg NH(4+) dm(-3) for Stentor
      coeruleus and 441.12 mg NH(4+) dm(-3) for Coleps hirtus. The ammonia ion
      concentration apparently is an important factor in the occurrence of these
      protozoan species in activated sludge.

PMID- 22976440
TI  - Biosurfactant production by marine bacterial isolates from the Venezuelan
      Atlantic Front.
AB  - Our purpose was to detect, isolate and characterize tensioactive agents with or
      without emulsifying activity from marine bacterial strains present in seawater
      and sediment samples from the Venezuelan Atlantic Front. Biosurfactants found in
      cell-free supernatants from all cultures presented high surface activity as they
      were able to reduce the water surface tension from 72 dynes cm(-1) to values
      between 41.7 and 33.9 dynes cm(-1). However, high indirect CMC values were
      registered for the most of these compounds (51.4%-56.1% v/v). Culture
      supernatants from S3 and S29 strains showed highest emulsifying activity in the
      dispersion assay with diesel oil (absorbance 1.06 and 1.18, respectively), while
      supernatant from the S10 strain induced the most stable oil-in-water emulsions
      with 16 degrees  and 25 degrees API crude oils. Only culture supernatant from S3
      strain was able to produce stable oil-in water emulsions with diesel oil and both
      type of crude oils.

PMID- 22976442
TI  - Unusual sensitivity to steroid treatment in intractable childhood epilepsy
      suggests GLUT1 deficiency syndrome.
AB  - Glucose transporter 1 (GLUT1) deficiency syndrome (DS) results from impaired
      glucose transport into brain. We describe the case of an 8-year-old girl with
      early-onset myoclonic epilepsy unresponsive to eight anticonvulsants. Oral
      steroid treatment achieved dramatic seizure control at the expense of Cushing
      syndrome and progressive fatty liver disease. Steroid withdrawal resulted in
      severe seizure exacerbation but was eventually enforced for lumbar puncture.
      GLUT1DS was diagnosed by hypoglycorrhachia and a heterozygous SLC2A1 mutation
      (Arg400His). A ketogenic diet resulted in effective seizure control. Steroids in
      GLUT1DS are unusual and unreported. Here a remarkable immediate and effective
      seizure control and a dose-independent unsuccessful steroid withdrawal indicated
      a potential GLUT1 sensitivity to steroids. We review the literature on
      GLUT1/steroid interactions and propose that unusual steroid sensitivity in
      intractable childhood epilepsy might be indicative for GLUT1DS.

PMID- 22976441
TI  - DNA damage-induced activation of ATM promotes beta-TRCP-mediated Mdm2
      ubiquitination and destruction.
AB  - The Mdm2 oncoprotein promotes p53 ubiquitination and destruction. Yet, exact
      molecular mechanisms of Mdm2 destruction itself, under DNA damaging conditions,
      remain unclear. Recently, we identified SCFbeta-TRCP as a novel E3 ligase that
      targets Mdm2 for ubiquitination and destruction in a Casein Kinase Idelta
      (CKIdelta)-dependent manner. However, it remains elusive how the beta
      TRCP/CKIdelta/Mdm2 signaling axis is regulated by DNA damage signals to govern
      p53 activity. Consistent with previous studies, we found that inactivation of the
      Ataxia Telangiectasia Mutated (ATM) kinase, in turn, impaired DNA damage-induced
      Mdm2 destruction. Although phosphorylation of Mdm2 at Ser395 (an ATM
      phosphorylation site) facilitated Mdm2 interaction with beta-TRCP, Ser395A-Mdm2
      was degraded non-distinguishably from WT-Mdm2 by SCFbeta-TRCP upon DNA damaging
      treatments. This indicates that in addition to phosphorylating Mdm2 at Ser395,
      ATM may govern Mdm2 stability through other unknown mechanisms. We further
      demonstrated that DNA damage-induced activation of ATM directly phosphorylated
      CKIdelta at two well-conserved S/TQ sites, which promotes CKIdelta nuclear
      localization to increase CKIdelta-mediated phosphorylation of Mdm2, thereby
      facilitating subsequent Mdm2 ubiquitination by SCFbeta-TRCP. Our studies provide
      a molecular mechanism of how ATM could govern DNA damage-induced destruction of
      Mdm2 in part by phosphorylating both Mdm2 and CKIdelta to modulate SCFbeta-TRCP
      mediated Mdm2 ubiquitination. Given the pivotal role of Mdm2 in the negative
      regulation of p53, this work will also provide a rationale for developing
      CKIdelta or ATM agonists as anti-cancer agents.

PMID- 22976443
TI  - Adherence to clusters of health behaviors and successful aging.
AB  - OBJECTIVE: Analyses examine the extent to which adherence to recommendations
      regarding health behaviors cluster among older adults, whether people who adhere
      to multiple health behaviors are more likely to age successfully than those who
      adhere to fewer health behaviors, and whether some health behavior clusters are
      more closely associated with successful aging than others. METHOD: Cross
      sectional data were collected using structured telephone interviews from 5,688
      persons aged 50 to 74 living in New Jersey. RESULTS: Prevalence odds ratio
      analyses indicated that differential cluster patterns exist. Logistic regression
      revealed that as the number of adherent behaviors increased so did the likelihood
      of aging successfully and that adherence to some health behavior clusters was
      more closely associated with successful aging than adherence to others.
      DISCUSSION: Although adherence to more health behaviors was associated with a
      greater likelihood of successful aging, it is possible to age successfully by
      adhering to specific clusters of health behaviors.

PMID- 22976444
TI  - Individualized behavioral assessments and maternal ratings of mastery motivation
      in mental age-matched toddlers with and without motor delay.
AB  - BACKGROUND: Mastery motivation is a precursor of future developmental outcomes.
      Evidence about whether toddlers with motor delay have lower mastery motivation is
      inconclusive. OBJECTIVE: The purpose of this study was to examine differences
      between mental age-matched toddlers with and without motor delay on various
      mastery motivation indicators. DESIGN: A mental age- and sex-matched case-control
      study was performed. METHODS: Twenty-two children with motor delay, aged 23 to 47
      months, and 22 children who were developing typically, aged 15 to 29 months, were
      recruited. Persistence and mastery pleasure were measured with behavioral tasks
      that were moderately challenging for each child and with maternal ratings using
      the Dimensions of Mastery Questionnaire (DMQ). The DMQ was rated by each child's
      mother based on her perception of her child's motivation. Two types of structured
      tasks (a puzzle and a cause-effect toy selected to be moderately challenging for
      each child) were administered in a laboratory setting and recorded on videos.
      Paired t tests or Wilcoxon signed rank tests were used to examine group
      differences in persistence and mastery pleasure (alpha=.007, 2-tailed). RESULTS:
      Children with motor delay were rated lower on DMQ persistence than the typically
      developing group, but they did not show significantly lower persistence on the
      structured tasks. There were no significant differences in mastery pleasure
      between the 2 groups on either measure. LIMITATIONS: Large within-sample
      variability on the tasks and small sample size makes subgroup analysis (eg,
      different severities) difficult. CONCLUSIONS: Toddlers with motor delay did not
      show lower persistence and pleasure when given tasks that were moderately
      challenging; however, their mothers tended to view them as having lower
      motivation. Clinicians and parents should provide appropriately challenging tasks
      to increase children's success and motivation.

PMID- 22976445
TI  - Intermanual transfer in training with an upper-limb myoelectric prosthesis
      simulator: a mechanistic, randomized, pretest-posttest study.
AB  - BACKGROUND: Intermanual transfer may improve prosthetic handling and acceptance
      if used in training soon after an amputation. OBJECTIVE: The purpose of this
      study was to determine whether intermanual transfer effects can be detected after
      training with a myoelectric upper-limb prosthesis simulator. DESIGN: A
      mechanistic, randomized, pretest-posttest design was used. PARTICIPANTS: A total
      of 48 right-handed participants (25 women, 23 men) who were able-bodied were
      randomly assigned to an experimental group or a control group. INTERVENTION: The
      experimental group performed a training program of 5 days' duration using the
      prosthesis simulator. To determine the improvement in skill, a test was
      administered before, immediately after, and 6 days after training. The control
      group only performed the tests. Training was performed with the unaffected arm,
      and tests were performed with the affected arm (the affected arm simulating an
      amputated limb). Half of the participants were tested with the dominant arm and
      half with the nondominant arm. MEASUREMENTS: Initiation time was defined as the
      time from starting signal until start of the movement, movement time was defined
      as the time from the beginning of the movement until completion of the task, and
      force control was defined as the maximal applied force on a deformable object.
      RESULTS: The movement time decreased significantly more in the experimental group
      (F2,92=7.42, P=.001, eta2(G)=.028) when compared with the control group. This
      finding is indicative of faster handling of the prosthesis. No statistically
      significant differences were found between groups with regard to initiation time
      and force control. We did not find a difference in intermanual transfer between
      the dominant and nondominant arms. LIMITATIONS: The training utilized
      participants who were able-bodied in a laboratory setting and focused only on
      transradial amputations. CONCLUSIONS: Intermanual transfer was present in the
      affected arm after training the unaffected arm with a myoelectric prosthesis
      simulator, and this effect did not depend on laterality. This effect may improve
      rehabilitation of patients with an upper-limb amputation.

PMID- 22976446
TI  - Global muscle strength but not grip strength predicts mortality and length of
      stay in a general population in a surgical intensive care unit.
AB  - BACKGROUND: Paresis acquired in the intensive care unit (ICU) is common in
      patients who are critically ill and independently predicts mortality and
      morbidity. Manual muscle testing (MMT) and handgrip dynamometry assessments have
      been used to evaluate muscle weakness in patients in a medical ICU, but similar
      data for patients in a surgical ICU (SICU) are limited. OBJECTIVE: The purpose of
      this study was to evaluate the predictive value of strength measured by MMT and
      handgrip dynamometry at ICU admission for in-hospital mortality, SICU length of
      stay (LOS), hospital LOS, and duration of mechanical ventilation. DESIGN: This
      investigation was a prospective, observational study. METHODS: One hundred ten
      patients were screened for eligibility for testing in the SICU of a large,
      academic medical center. The Acute Physiology and Chronic Health Evaluation
      (APACHE) II score, diagnoses, and laboratory data were collected. Measurements
      were obtained by MMT quantified with the sum (total) score on the Medical
      Research Council Scale and by handgrip dynamometry. Outcome data, including in
      hospital mortality, SICU LOS, hospital LOS, and duration of mechanical
      ventilation, were collected for all participants. RESULTS: One hundred seven
      participants were eligible for testing; 89% were tested successfully at a median
      of 3 days (25th-75th percentiles=3-6 days) after admission. Sedation was the most
      frequent barrier to testing (70.6%). Manual muscle testing was identified as an
      independent predictor of mortality, SICU LOS, hospital LOS, and duration of
      mechanical ventilation. Grip strength was not independently associated with these
      outcomes. LIMITATIONS: This study did not address whether muscle weakness
      translates to functional outcome impairment. CONCLUSIONS: In contrast to handgrip
      strength, MMT reliably predicted in-hospital mortality, duration of mechanical
      ventilation, SICU LOS, and hospital LOS.

PMID- 22976447
TI  - Move to improve: the feasibility of using an early mobility protocol to increase
      ambulation in the intensive and intermediate care settings.
AB  - BACKGROUND: Prolonged bed rest in hospitalized patients leads to deconditioning,
      impaired mobility, and the potential for longer hospital stays. OBJECTIVE: The
      purpose of this study was to determine the effectiveness of a nurse-driven
      mobility protocol to increase the percentage of patients ambulating during the
      first 72 hours of their hospital stay. DESIGN: A quasi-experimental design was
      used before and after intervention in a 16-bed adult medical/surgical intensive
      care unit (ICU) and a 26-bed adult intermediate care unit (IMCU) at a large
      community hospital. METHOD: A multidisciplinary team developed and implemented a
      mobility order set with an embedded algorithm to guide nursing assessment of
      mobility potential. Based on the assessments, the protocol empowers the nurse to
      consult physical therapists or occupational therapists when appropriate. Daily
      ambulation status reports were reviewed each morning to determine each patient's
      activity level. Retrospective and prospective chart reviews were performed to
      evaluate the effectiveness of the protocol for patients 18 years of age and older
      who were hospitalized 72 hours or longer. RESULTS: In the 3 months prior to
      implementation of the Move to Improve project, 6.2% (12 of 193) of the ICU
      patients and 15.5% (54 of 349) of the IMCU patients ambulated during the first 72
      hours of their hospitalization. During the 6 months following implementation,
      those rates rose to 20.2% (86 of 426) and 71.8% (257 of 358), respectively.
      LIMITATIONS: The study was carried out at only one center. CONCLUSION: The
      initial experience with a nurse-driven mobility protocol suggests that the rate
      of patient ambulation in an adult ICU and IMCU during the first 72 hours of a
      hospital stay can be increased.

PMID- 22976448
TI  - Reliability of six physical performance tests in older people with dementia.
AB  - BACKGROUND: Physical performance tests are important for assessing the effect of
      physical activity interventions in older people with dementia, but their
      psychometric properties have not been systematically established within this
      specific population. OBJECTIVE: The purpose of this study was to determine the
      relative and absolute test-retest reliability of the 6-m walk test, the figure-of
      Eight Walk Test (F8W), the Timed "Up & Go" Test (TUG), the Frailty and Injuries:
      Cooperative Studies of Intervention Techniques-4 (FICSIT-4) Balance Test, the
      Chair Rise Test (CRT), and the Jamar dynamometer. These tests are used to assess
      gait speed, dynamic balance, functional mobility, static balance, lower-limb
      strength, and grip strength, respectively. DESIGN: This investigation was a
      prospective, nonexperimental study. METHODS: Older people with dementia (n=58,
      age range=70-92 years) performed each test at baseline and again after 1 week.
      Intraclass correlation coefficients (ICC), standard error of measurement (SEM),
      minimal detectable change (MDC), and log-transferred limits of agreement of Bland
      Altman plots were calculated. RESULTS: The relative reliability of the F8W, TUG,
      and Jamar dynamometer was excellent (ICC=.90-.95) and good for the 6-m walk test,
      FICSIT-4, and CRT (ICC=.79-.86). The SEMs and MDCs were large for all tests. The
      absolute reliability of the TUG and CRT was significantly influenced by the level
      of cognitive functioning (as assessed with the Mini-Mental State Examination
      [MMSE]). LIMITATIONS: The specific etiology of dementia was not obtained.
      CONCLUSIONS: The physical performance tests evaluated are useful for detecting
      differences in performance between older people with mild to moderate dementia
      and, therefore, are suitable for cross-sectional or controlled intervention
      studies. They appear less suitable to monitor clinically relevant intra
      individual performance changes. Future studies should focus on the development of
      more sensitive tests and the identification of criteria for clinically relevant
      changes in this rapidly growing population.

PMID- 22976449
TI  - Rhodium-catalyzed cross-aldol reaction: in situ aldehyde-enolate formation from
      allyloxyboranes and primary allylic alcohols.

PMID- 22976452
TI  - The binding affinity of amino acid-protein: hydroxyproline binding site I on
      human serum albumin.
AB  - The binding affinity between hydroxyproline (Hyp) and human serum albumin (HSA)
      was investigated under simulated physiological conditions, using molecular
      modeling in combination with steady-state fluorescence, synchronous fluorescence,
      time-resolved fluorescence, UV-vis absorption, circular dichroism (CD), and
      Fourier transform infrared (FT-IR) spectroscopy. Molecular modeling studies
      suggested that the Hyp molecule was situated within subdomain IIA of HSA. The
      fluorescence quenching analysis indicated that the fluorescence of HSA was
      quenched by Hyp with a dynamic quenching mechanism. The binding constants were
      calculated according to Scatchard's equation and implied that Hyp can bind to
      different binding sites on HSA. The thermodynamic analysis implied that
      hydrophobic forces were the main interaction in the Hyp-HSA system, which was
      found to be in line with the results of molecular modeling. Furthermore, the
      conformational structure of HSA was changed with various amounts of Hyp, which
      was confirmed by synchronous fluorescence, UV-vis absorption, CD, and FT-IR
      spectra.

PMID- 22976453
TI  - Characteristics of physicians engaged in basic science: a questionnaire survey of
      physicians in basic science departments of a medical school in Japan.
AB  - The number of physicians engaged in basic science and teaching is sharply
      decreasing in Japan. To alleviate this shortage, central government has increased
      the quota of medical students entering the field. This study aimed to determine
      the characteristics of physicians who are engaged in basic science in efforts to
      recruit talent. A questionnaire was distributed to all 30 physicians in the basic
      science departments of Juntendo University School of Medicine. Question items
      inquired about sex, years since graduation, years between graduation and time
      entering basic science, clinical experience, recommending the career to medical
      students, expected obstacles to students entering basic science, efforts to
      inspire students in research, increased number of lectures and practical training
      sessions on research, and career choice satisfaction. Correlations between the
      variables were examined using chi(2) tests. Overall, 26 physicians, including 7
      female physicians, returned the questionnaire (response rate 86.7%). Most
      physicians were satisfied with their career choice. Medical students were deemed
      not to choose basic science as their future career, because they aimed to become
      clinicians and because they were concerned about salary. Women physicians in
      basic science departments were younger than men. Women physicians also considered
      themselves to make more efforts in inspiring medical students to be interested in
      research. Moreover, physicians who became basic scientists earlier in their
      career wanted more research-related lectures in medical education. Improving
      physicians' salaries in basic science is important to securing talent. In
      addition, basic science may be a good career path for women physicians to follow.

PMID- 22976451
TI  - How do plants make mitochondria?
AB  - Plant mitochondria can differ in size, shape, number and protein content across
      different tissue types and over development. These differences are a result of
      signaling and regulatory processes that ensure mitochondrial function is tuned in
      a cell-specific manner to support proper plant growth and development. In the
      last decade, the processes involved in mitochondrial biogenesis are becoming
      clearer, including; how dormant seeds transition from empty promitochondria to
      fully functional mitochondria with extensive cristae structures and various
      biochemical activities, the regulation of nuclear genes encoding mitochondrial
      proteins via regulators of the diurnal cycle in plants, the mitochondrial stress
      response, the targeting of proteins to mitochondria and other organelles and
      connections between the respiratory chain and protein import complexes. All these
      findings indicate that mitochondrial function is a part of an integrated cellular
      network, and communication between mitochondria and other cellular processes
      extends beyond the known exchange or transport of metabolites. Our current
      knowledge now needs to be used to gain more insight into the molecular components
      at various levels of this hierarchical and complex regulatory and communication
      network, so that mitochondrial function can be predicted and modified in a
      rational manner.

PMID- 22976454
TI  - Factors influencing the biochemical markers for predicting mammalian oocyte
      quality.
AB  - The need for accurate selection of the best oocytes for in vitro fertilization
      protocols and thus, production of embryos has driven the search for oocyte
      quality markers from morphological criteria to biochemical parameters. Current
      studies are focused on the biochemical constituents of the follicular fluid and
      gene expression profiling of the cumulus cells. These parameters are, however,
      affected by factors that must be considered before making a judgment of the
      oocyte's quality. These includes factors such as the type of hormonal stimulation
      protocol, age of oocyte donor and heat stress on the donor, all of which have
      been reported to influence the concentrations of many hormones, apolipoproteins,
      metabolites, fatty acids and growth factors in the follicular fluid and the
      expression of several genes in the cumulus cells. Another important point to note
      is species variation in the response to these extraneous influences, which thus
      calls for species targeted investigations. As reports are still scanty and
      investigations assumed to be very keen, we employed this review paper to bring
      attention of researchers and clinicians to those factors that may come to bear on
      the outcome of their investigations on oocyte and embryo quality.

PMID- 22976450
TI  - How to build functional thylakoid membranes: from plastid transcription to
      protein complex assembly.
AB  - Chloroplasts are the endosymbiotic descendants of cyanobacterium-like
      prokaryotes. Present genomes of plant and green algae chloroplasts (plastomes)
      contain ~100 genes mainly encoding for their transcription-/translation
      machinery, subunits of the thylakoid membrane complexes (photosystems II and I,
      cytochrome b (6) f, ATP synthase), and the large subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase. Nevertheless, proteomic studies have
      identified several thousand proteins in chloroplasts indicating that the majority
      of the plastid proteome is not encoded by the plastome. Indeed, plastid and host
      cell genomes have been massively rearranged in the course of their co-evolution,
      mainly through gene loss, horizontal gene transfer from the
      cyanobacterium/chloroplast to the nucleus of the host cell, and the emergence of
      new nuclear genes. Besides structural components of thylakoid membrane complexes
      and other (enzymatic) complexes, the nucleus provides essential factors that are
      involved in a variety of processes inside the chloroplast, like gene expression
      (transcription, RNA-maturation and translation), complex assembly, and protein
      import. Here, we provide an overview on regulatory factors that have been
      described and characterized in the past years, putting emphasis on mechanisms
      regulating the expression and assembly of the photosynthetic thylakoid membrane
      complexes.

PMID- 22976456
TI  - Development of critically reflective dialogues in communities of health
      professionals.
AB  - Critically reflective dialogues (CRD) are important for knowledge sharing and
      creating meaning in communities. CRD includes different aspects: being open about
      mistakes, critical opinion sharing, asking for and giving feedback,
      experimentation, challenging groupthink and research utilisation. In this article
      we explore whether CRD aspects change over time, through a study of two dialogues
      each from six different communities of veterinary health professionals. Change
      was studied from the perspective of observations, through analysing transcripts
      of dialogues, and from the perspective of community members' perceptions, through
      an evaluative discussion with members. The results showed that some communities
      became more open about mistakes, a finding that is related to an increase in
      trust. Other observed aspects of CRD seemed to be fairly stable over time.
      Community members perceived research utilisation and asking for and giving
      feedback to have been increased. From an analysis of perceptions of the community
      members it emerged that limited interaction could be associated with the
      epistemological conceptions of community members. 

PMID- 22976457
TI  - MALDI in-source decay, from sequencing to imaging.
AB  - Matrix-assisted laser desorption/ionization (MALDI) is now a mature method
      allowing the identification and, more challenging, the quantification of
      biopolymers (proteins, nucleic acids, glycans, etc). MALDI spectra show mostly
      intact singly charged ions. To obtain fragments, the activation of singly charged
      precursors is necessary, but not efficient above 3.5 kDa, thus making MALDI MS/MS
      difficult for large species. In-source decay (ISD) is a prompt fragmentation
      reaction that can be induced thermally or by radicals. As fragments are formed in
      the source, precursor ions cannot be selected; however, the technique is not
      limited by the mass of the analyzed compounds and pseudo MS3 can be performed on
      intense fragments. The discovery of new matrices that enhance the ISD yield,
      combined with the high sensitivity of MALDI mass spectrometers, and software
      development, opens new perspectives. We first review the mechanisms involved in
      the ISD processes, then discuss ISD applications like top-down sequencing and
      post-translational modifications (PTMs) studies, and finally review MALDI-ISD
      tissue imaging applications.

PMID- 22976458
TI  - Bioinformatic analysis of data generated from MALDI mass spectrometry for
      biomarker discovery.
AB  - In this chapter we first describe the applications of matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) in biomarker discovery.
      After a summary of the general analysis pipeline of MALDI MS data, each step of
      the pipeline will be elaborated in detail. In particular we try to provide a
      categorization of existing solutions with the hope that the reader can obtain a
      global picture on this topic. In addition we show how to apply such an analysis
      pipeline in protein and glycan profiling for biomarker discovery and for a deeper
      understanding of diseases. Finally we discuss the limitations of current analysis
      methods and the perspectives of future research.

PMID- 22976459
TI  - Synthesis and chirality of amino acids under interstellar conditions.
AB  - Amino acids are the fundamental building blocks of proteins, the biomolecules
      that provide cellular structure and function in all living organisms. A majority
      of amino acids utilized within living systems possess pre-specified orientation
      geometry (chirality); however the original source for this specific orientation
      remains uncertain. In order to trace the chemical evolution of life, an
      appreciation of the synthetic and evolutional origins of the first chiral amino
      acids must first be gained. Given that the amino acids in our universe are likely
      to have been synthesized in molecular clouds in interstellar space, it is
      necessary to understand where and how the first synthesis might have occurred.
      The asymmetry of the original amino acid synthesis was probably the result of
      exposure to chiral photons in the form of circularly polarized light (CPL), which
      has been detected in interstellar molecular clouds. This chirality transfer
      event, from photons to amino acids, has been successfully recreated
      experimentally and is likely a combination of both asymmetric synthesis and
      enantioselective photolysis. A series of innovative studies have reported
      successful simulation of these environments and afforded production of chiral
      amino acids under realistic circumstellar and interstellar conditions:
      irradiation of interstellar ice analogues (CO, CO2, NH3, CH3OH, and H2O) with
      circularly polarized ultraviolet photons at low temperatures does result in
      enantiomer enriched amino acid structures (up to 1.3% ee). This topical review
      summarizes current knowledge and recent discoveries about the simulated
      interstellar environments within which amino acids were probably formed. A
      synopsis of the COSAC experiment onboard the ESA cometary mission ROSETTA
      concludes this review: the ROSETTA mission will soft-land on the nucleus of the
      comet 67P/Churyumov-Gerasimenko in November 2014, anticipating the first in situ
      detection of asymmetric organic molecules in cometary ices. 

PMID- 22976460
TI  - Closed-shell and open-shell 2D nanographenes.
AB  - This chapter describes a series of two-dimensional (2D) expanded arene networks,
      also known as nanographenes, with either closed-shell or open-shell electronic
      structure in the ground state. These systems are further categorized into three
      classes on a basis of different edge structures: those with zigzag edges only,
      those with armchair edges only, and those possessing both. Distinctive physical
      properties of these 2D aromatic systems are closely related to their structural
      characteristics and provide great potential for them as materials for different
      applications. 

PMID- 22976461
TI  - Risk factors and clinical significance of trauma-induced coagulopathy in ICU
      patients with severe trauma.
AB  - OBJECTIVE: To investigate the incidence and risk factors for trauma-induced
      coagulopathy (TIC) and the impact of TIC on outcomes of patients with severe
      trauma admitted to an emergency intensive care unit. METHODS: We retrospectively
      reviewed clinical data from 223 patients with severe trauma admitted to emergency
      intensive care unit within 24 h after injury. Injury Severity Score (ISS), Acute
      Physiology and Chronic Health Evaluation II score, coagulation function, routine
      blood and biochemical tests, and blood gas parameters were obtained from medical
      records. Patients were divided into two groups according to the presence or
      absence of coagulopathy. ISS, Acute Physiology and Chronic Health Evaluation II
      score, and the incidence rates of hypothermia and tissue hypoperfusion were
      compared. The risk factors of TIC were analyzed and a multivariate logistic
      regression equation was developed. Coagulation function and the incidence of TIC
      were also compared between surviving and dead patients. RESULTS: Overall, 52/223
      (23.3%) patients fulfilled the diagnostic criteria for TIC. Their mortality rate
      was significantly higher than that of patients without coagulopathy (36.5 vs.
      9.4%, P<0.01). ISS, incidence rates of hypothermia and tissue hypoperfusion, and
      the prevalence of severe traumatic brain injury were significantly higher
      (P<0.01), whereas Glasgow Coma Scale, hemoglobin, hematocrit, and platelet counts
      were significantly lower (P<0.01) in patients with coagulopathy than those
      without. Base deficit at least 6, Glasgow Coma Scale 8 or less, and platelet
      count were independent risk factors for TIC. Compared with surviving patients,
      the patients who died had significantly reduced coagulation function. CONCLUSION:
      The incidence of TIC is particularly high among patients with severe trauma. TIC
      is associated with increased ISS, brain injury, shock and hypothermia, and
      mortality.

PMID- 22976462
TI  - The role of an emergency department short-stay ward in the management of dengue
      fever: a case-control study in a university hospital.
AB  - OBJECTIVE: Dengue fever is endemic in Malaysia and poses a significant problem to
      the national health system. Because of its nonspecific clinical features, it
      creates clinical and administrative uncertainties. We evaluated the role of an
      emergency department short-stay ward (EDSSW) in the management of dengue fever in
      the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). METHODS: A
      retrospective study was carried out on suspected dengue patients who were
      admitted to UKMMC EDSSW, between January and March 2010. Data were retrieved from
      the EDSSW Monthly Census Book and patients' medical records. Patients were
      categorized as follows: group 1, which included patients who received treatment
      in the EDSSW only, and group 2, which included patients who received initial
      treatment in EDSSW and were subsequently admitted to the inpatient (IP) wards.
      RESULTS: A total of 147 patients' records were available. The total length of
      stay was 32.2 h in group 1 and 100.5 h in group 2. For group 2 patients, a median
      of 21.8 h was spent in EDSSW and 78.8 h was spent in IP. All patients in group 1
      and group 2 were discharged well. The total EDSSW stay was 4309 patient-hours; IP
      stay totalled 5137 patient-hours. The use of the EDSSW reduced the IP burden in
      managing dengue by 45.6%. CONCLUSION: EDSSW limit the number and burden of dengue
      patients requiring formal IP admissions while acting as a 'safety net' for
      inappropriate discharges and unnecessary admissions.

PMID- 22976463
TI  - Patients who leave before being seen in an urgent care setting.
AB  - OBJECTIVES: This study attempts to quantify and characterize the patients who
      leave before being seen (LBBS) by a physician in an urgent care setting. METHODS:
      A retrospective chart review was performed of visits between 1 May 2008 and 31
      March 2010, at five urgent care centers (UCC). Variables extracted included sex,
      age, date and time of visit, and the chief complaint. A log of patient reports of
      the reasons for LBBS was reviewed. The relationship between waiting times and
      LBBS was analyzed for visits between 1 April 2012 and 30 June 2012. RESULTS: LBBS
      visits comprised 2.0% of the total of 378 332 visits. The left-before-being-seen
      group had a higher percentage of men (P<0.0001), and young and middle-aged
      patients (P<0.0001). The left-before-being-seen group had more visits in the
      overnight and daytime shifts and fewer visits on weekends (P<0.0001). Of those 10
      409 patients who reported reasons at discharge, 43% cited a long wait time and
      39% did not want to pay the copay. In the group for which wait times were
      available, 92.3% were triaged within 30 min and yet 60% of those who gave reasons
      stated that they were leaving because they had waited too long. CONCLUSION: The
      rates of leaving before being seen in urgent care were comparable with the lower
      end of those reported by emergency departments. Patients who left before being
      seen in UCC were most likely to be working-age adults during daytime hours. In
      UCC, LBBS is often related to perceived, rather than actual, long wait times.

PMID- 22976464
TI  - Acute angioedema:  recognition and management in the emergency department.
AB  - Angioedema is characterized by localized swelling of subcutaneous tissues or
      mucosa of the upper respiratory or gastrointestinal tract. Laryngeal involvement
      may threaten airway patency and can be fatal if not addressed promptly. There are
      several distinct subtypes of angioedema, caused by different pathological
      processes involving a range of proinflammatory mediators. In the emergency
      department, it is essential not only that acute angioedema is identified as
      quickly as possible but also that the likely working diagnosis is established so
      that the most effective treatment may be administered to resolve potentially life
      threatening swelling. In this paper, we present an overview of the various types
      of angioedema, and offer a practical diagnostic and therapeutic approach to their
      management.

PMID- 22976465
TI  - Education in research: results of a survey commissioned by the research committee
      of the European Society of Radiology.
AB  - OBJECTIVES: The purpose of this investigation was to assess the current status of
      education in research in Europe with a view to making recommendations and
      improvements in the status of education in research for involved stakeholders.
      METHODS: A questionnaire concerning education in research in Europe was sent to
      the National Society representatives, to Subspecialty Societies and potentially
      interested ESR committees. Questions were posed to assess the current status and
      to explore a desired future status for a broad base of interested stakeholders.
      Questions related to training (general status), research drivers, researcher
      recruitment, contents of research education, education methods, flexibility in
      research career planning, scientific network building, scientific research
      funding and measuring outcomes of research education. RESULTS: The most
      pronounced inadequacies were perceived in the following areas: promotion of
      clinical scientists, promotion of material sciences, earlier recruitment of
      researchers, laboratory training, flexible and adaptable schedules, career
      planning by research group leaders, network building by funding agencies, funding
      by organ-based radiology sections and outcome measurement by professional
      surveys. CONCLUSIONS: The results of this questionnaire indicate that the subject
      of education in research methodology, career structure and career outcome need
      promotion. The important role of professional societies in supporting these
      changes is emphasised. MAIN MESSAGES: * In the immediate future it is recommended
      that radiology researchers should maintain individual responsibility for their
      career path, but this should be actively facilitated by their peer group. * A
      research career should be encouraged to commence during residency and include an
      increased proportion of wet laboratory work focussed on biologic topics. *
      Production of peer-reviewed publications should remain a high priority. *
      Flexibility in professional schedules should be facilitated to allow dedicated
      periods for formal research. * Research programmes should be measured by the
      number of successful research-based personnel involved, in addition to the
      bibliography.

PMID- 22976467
TI  - Synthesis and chromatography-free purification of PNA-PEO conjugates for the
      functionalisation of gold sensors.
AB  - Peptide Nucleic Acids (PNAs) linked to high molecular weight (MW) poly(ethylene
      oxide) (PEO) derivatives could be useful conjugates for the direct
      functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)
      based DNA sensing. However their use is hampered by the difficulty to obtain them
      through a convenient and economical route. In this work we compared three
      synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a) a 15
      mer PNA sequence as the probe complementary to genomic DNA of ]Mycobacterium
      tuberculosis, (b) a PEO moiety (2 or 5 KDa MW) and (c) a terminal trityl
      protected thiol necessary (after acidic deprotection) for grafting to gold
      surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino
      terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa
      MW) carrying a Trt-cysteine at one end and a carboxyl group at the other end. The
      reaction was carried out either in solution, using HATU or PyOxim as coupling
      agents, or through the solid-phase approach, with 49.6%, 100% and 5.2% yield,
      respectively. A differential solvent extraction strategy for product purification
      without the need for chromatography is described. The ability of the 5 KDa PEO
      conjugate to function as a probe for complementary DNA detection was demonstrated
      using a Grating-Coupling Surface Plasmon Resonance (GC-SPR) system. The optimized
      PEO conjugation and purification protocols are economical and simple enough to be
      reproduced also within laboratories that are not highly equipped for chemical
      synthesis.

PMID- 22976466
TI  - Genome-wide aberrant DNA methylation of microRNA host genes in hepatocellular
      carcinoma.
AB  - Mature microRNAs (miRNAs) are a class of small non-coding RNAs involved in
      posttranslational gene silencing. Previous studies found that downregulation of
      miRNAs is a common feature observed in solid tumors, including hepatocellular
      carcinoma (HCC). We employed a genome-wide approach to test the hypothesis that
      DNA methylation alterations in miRNA host genes may cause deregulated miRNA
      expression in HCC. We analyzed tumor and adjacent non-tumor tissues from 62
      Taiwanese HCC cases using Infinium HumanMethylation27 DNA Analysis BeadChips that
      include 254 CpG sites covering 110 miRNAs from 64 host genes. Expression levels
      of three identified miRNAs (miR-10a, miR-10b and miR-196b) were measured in a
      subset of 37 HCC tumor and non-tumor tissues. After Bonferroni adjustment, a
      total of 54 CpG sites from 27 host genes significantly differed in DNA
      methylation levels between tumor and adjacent non-tumor tissues with 53 sites
      significantly hypermethylated in tumor tissues. Among the 54 significant CpG
      sites, 15 sites had more than 2-fold tumor/non-tumor changes, 17 sites had
      differences > 10%, and 10 sites had both features [including 8 significantly
      hypermethylated CpG sites in the host genes of miR-10a, miR-10b and miR-196b
      (HOXB4, HOXD4 and HOXA9, respectively)]. Significant downregulation of miR-10a
      was observed in tumor compared with non-tumor tissues (0.50 vs. 1.73, p = 0.031).
      The concordance for HOXB4 methylation alteration and dysregulation of miR-10a was
      73.5%. No significant change was observed for miR-10b expression. Unexpectedly,
      miR-196b was significantly upregulated in tumor compared with non-tumor tissues
      (p = 0.0001). These data suggest that aberrant DNA methylation may lead to
      dysregulation of miR-10a in HCC tumor tissues.

PMID- 22976468
TI  - Synthesis of highly substituted oxazoles through iodine(III)-mediated reactions
      of ketones with nitriles.
AB  - In the presence of trifluoromethanesulfonic acid (TfOH) or bis(trifluoromethane
      sulfonyl)imide (Tf2NH), iodosobenzene (PhI=O) efficiently promoted the reactions
      of dicarbonyl compounds as well as monocarbonyl compounds with nitriles to give
      2,4-disubstituted and 2,4,5-trisubstituted oxazole in a single step under the
      mild conditions.

PMID- 22976469
TI  - Chemical composition and biological activities of the essential oils from
      Duguetia lanceolata St. Hil. barks.
AB  - Essential oils of Duguetia lanceolata barks, obtained at 2 (T2) and 4 h (T4),
      were identified by gas chromatography and gas chromatography/mass spectrometry.
      beta-elemene (12.7 and 14.9%), caryophyllene oxide (12.4 and 10.7%) and beta
      selinene (8.4 and 10.4%) were the most abundant components in T2 and T4,
      respectively. The essential oils inhibited the growth of Staphylococcus aureus,
      Streptococcus pyogenes, Escherichia coli and Candida albicans. The essential oils
      were cytotoxic against brine shrimp. The extraction time influenced the chemical
      composition and biological activities of essential oils obtained from the barks
      of D. lanceolata.

PMID- 22976470
TI  - Primary investigation of the preparation of nanoparticles by precipitation.
AB  - The absorption, distribution, biotransformation and excretion of a drug involve
      its transport across cell membranes. This process is essential and influenced by
      the characteristics of the drug, especially its molecular size and shape,
      solubility at the site of its absorption, relative lipid solubility, etc. One of
      the progressive ways for increasing bioavaibility is a nanoparticle preparation
      technique. Cholesterol, cholestenolone and pregnenolone acetate as model active
      pharmaceutical ingredients and some of the commonly used excipients as
      nanoparticle stabilizers were used in the investigated precipitation method that
      was modified and simplified and can be used as an effective and an affordable
      technique for the preparation of nanoparticles. All 120 prepared samples were
      analyzed by means of dynamic light scattering (Nanophox). The range of the
      particle size of the determined 100 nanoparticle samples was from 1 nm to 773 nm,
      whereas 82 samples contained nanoparticles of less than 200 nm. Relationships
      between solvents and used excipients and their amount are discussed.

PMID- 22976471
TI  - Cyclizations producing hydrindanones with two methyl groups at the juncture
      positions mediated by samarium diiodide and electrolysis.
AB  - One-electron reductive intramolecular cyclization of enones with ketones or
      aldehydes mediated by samarium diiodide and electrolysis to afford cis-trimethyl-
      hydrindanolones. The reactions gave selectivities ranging from 1:1 to 100:0
      depending on the conditions.

PMID- 22976472
TI  - Genetic and epigenetic contribution to complex traits.
AB  - Much of the recent advances in functional genomics owe to developments in next
      generation sequencing technology, which has contributed to the exponential
      increase of genomic data available for different human disease and population
      samples. With functional sequencing assays available to query both the
      transcriptome and the epigenome, annotation of the non-coding, regulatory genome
      is steadily improving and providing means to interpret the functional
      consequences of genetic variants associated with human complex traits. This has
      highlighted the need to better understand the normal variation in various
      cellular phenotypes, such as epigenetic modifications, and their
      transgenerational inheritance. In this review, we discuss different aspects of
      epigenetic variation in the context of DNA sequence variation and its
      contribution to complex phenotypes.

PMID- 22976473
TI  - Interrogating the major histocompatibility complex with high-throughput genomics.
AB  - The major histocompatibility complex (MHC) region on the short arm of chromosome
      6 harbors the largest number of replicated associations across the human genome
      for a wide range of diseases, but the functional basis for these associations is
      still poorly understood. One fundamental challenge in fine-mapping associations
      to functional alleles is the enormous sequence diversity and broad linkage
      disequilibrium of the MHC, both of which hamper the cost-effective interrogation
      in large patient samples and the identification of causal variants. In this
      review, we argue that there is now a valuable opportunity to leverage existing
      genome-wide association study (GWAS) datasets for in-depth investigation to
      identify independent effects in the MHC. Application of imputation to GWAS data
      facilitates comprehensive interrogation of the classical human leukocyte antigen
      (HLA) loci. These datasets are, in many cases, sufficiently large to give
      investigators the ability to disentangle effects at different loci. We also
      explain how querying variation at individual amino acid positions for association
      can be powerful and expand traditional analyses that focus only on the classical
      HLA types.

PMID- 22976476
TI  - Highlights of the annual scientific meeting of the 19th congress of the European
      Society of Musculoskeletal Radiology (ESSR) 2012.

PMID- 22976475
TI  - Development of poly(vinyl acetate-methylacrylic acid)/chitosan/Fe3O4
      nanoparticles for the diagnosis of non-alcoholic steatohepatitis with magnetic
      resonance imaging.
AB  - Non-alcoholic steatohepatitis is a burgeoning health problem. To diagnose NASH
      with magnetic resonance imaging (MRI), an effective contrast agent, a stable
      suspension of superparamagnetic Fe(3)O(4) nanoparticles, were newly developed.
      The negatively charged Fe(3)O(4) nanoparticles were coated with positive chitosan
      (CS) firstly, and then assembled with poly(vinyl acetate-methylacrylic acid)
      (P(VAc-MAA)). Transmission electron microscope and dynamic light scattering
      confirmed that the obtained P(VAc-MAA)/CS/Fe(3)O(4) nanoparticles had a spherical
      or ellipsoidal morphology with an average diameter in the range of 14-20 nm. The
      superparamagnetic property and spinel structure of the Fe(3)O(4) nanoparticles
      were well preserved due to the protection of the P(VAc-MAA)/CS layers on the
      surface of the Fe(3)O(4) nanoparticles. The in vivo rat experiments confirmed
      that the P(VAc-MAA)/CS/Fe(3)O(4) nanoparticles were an effective contrast agent
      for MRI to diagnose NASH.

PMID- 22976477
TI  - Postmortem imaging exposed: an aid in MR imaging of musculoskeletal structures.
AB  - OBJECTIVE: To identify factors that influence the quality of postmortem magnetic
      resonance (MR) images of musculoskeletal (MSK) structures as described in the
      literature, and to evaluate the extent to which these MR images are affected.
      MATERIALS AND METHODS: Four useful studies were retrieved from a PubMed and
      EMBASE search, covering the literature up to 1 March 2012. Three additional
      studies were included after a manual search from reference lists. RESULTS: Four
      human studies and three animal studies are considered in this review. Postmortem
      MRI quality can be affected by storage temperature, repeated freezing and thawing
      and fixation. Provided there was an adequate, but above-freezing storage
      temperature, postmortem changes in fresh cadavers did not appear to affect the MR
      image quality of MSK structures up to 14 days after death. Image contrast, signal
      intensities, and relaxation times are temperature-dependent, regardless of
      whether the specimen was fresh or postmortem for up to 7 days. Bad image quality
      can occur owing to accelerated autolysis. Freezing and thawing did not affect
      image quality, unless repeated too often, or whenever a heating pad was used to
      speed up the thawing process. Conventional formalin-based fixation leads to
      swelling of soft tissue and fluid accumulation in joints, and therefore to
      deteriorated images, with image quality just sufficient to visualize gross
      anatomy. CONCLUSION: Various factors were identified that affect postmortem MR
      image quality of MSK structures. Postmortem MR image quality was good, except for
      images of the fixated specimen. Freezing is the preferred method of conservation
      for specimens that are to be subjected to postmortem MRI.

PMID- 22976478
TI  - [Bone metastases treatment strategies].
AB  - The primary goals of multimodal, interdisciplinary treatment of bone metastases
      are to achieve mobility, pain relief, and improve quality of life. In cooperation
      with radiotherapists and oncologists, an individual therapy plan has to be
      designed. As bone metastases are a sign of a systemic spread of the disease, cure
      is not possible in nearly all cases. A singular bone metastasis of a renal cell
      carcinoma may be regarded as an exemption, where wide resection might cure the
      patient. The extent of the operation should be based on the 3S principle "save,
      short & simple". The prognosis of survival should influence the treatment regime.
      If it is unclear whether a bone metastasis or a primary bone tumor is present, a
      biopsy is required.

PMID- 22976479
TI  - Precisely tunable photonic crystals from rapidly self-assembling brush block
      copolymer blends.
AB  - Colorful: enabled by their reduced capacity for chain entanglement, high
      molecular-weight brush block copolymers can rapidly self-assemble to photonic
      crystals. The blending of two polymers of different molecular weight can
      predictably modulate the sizes of the polymer domains, giving rise to a facile
      means of precision tuning of these photonic-band-gap materials.

PMID- 22976474
TI  - A meta-analysis of genome-wide association studies of breast cancer identifies
      two novel susceptibility loci at 6q14 and 20q11.
AB  - Genome-wide association studies (GWAS) of breast cancer defined by hormone
      receptor status have revealed loci contributing to susceptibility of estrogen
      receptor (ER)-negative subtypes. To identify additional genetic variants for ER
      negative breast cancer, we conducted the largest meta-analysis of ER-negative
      disease to date, comprising 4754 ER-negative cases and 31 663 controls from three
      GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative
      cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer
      Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European
      ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative
      cases; 2745 controls). We performed in silico replication of 86 SNPs at P <= 1 *
      10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease)
      and 16 057 controls of Japanese, Latino and European ancestry. We identified two
      novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was
      associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1
      * 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08,
      P = 1.3 * 10(-6)) based on 17 869 cases and 43 745 controls and no association
      with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902
      controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR =
      1.12; P = 1.1 * 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 * 10(-5))
      and ER-negative (OR = 1.16, P = 2.5 * 10(-7)) disease. We also confirmed three
      known loci associated with ER-negative (19p13) and both ER-negative and ER
      positive breast cancer (6q25 and 12p11). Our results highlight the value of large
      scale collaborative studies to identify novel breast cancer risk loci.

PMID- 22976480
TI  - Palladium-catalyzed cross-coupling of unactivated alkenes with acrylates:
      application to the synthesis of the C13-C21 fragment of palmerolide A.

PMID- 22976481
TI  - A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger
      mediated ring-closure.
AB  - Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10
      membered cyclic tripeptides containing alpha-, beta- or gamma-amino acid residues
      is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and
      tripeptides--recognized as difficult targets--were obtained in moderate to good
      yields according to a straightforward sequence. Empirical force-field
      calculations were undertaken to determine their conformational behaviors and
      showed high levels of similarity with X-ray results. A computational study at the
      B3LYP/6-31+G** level of theory afforded information regarding the impact of the
      sequence, ring-size and substitution on the activation barriers for the
      cyclization of azido peptide thioesters.

PMID- 22976482
TI  - Secondary metabolites from a culture of the fungus Neosartorya pseudofischeri and
      their in vitro cytostatic activity in human cancer cells.
AB  - Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5
      dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative
      (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from
      the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in
      vitro growth inhibitory activity that ranged between the activities of etoposide
      and carboplatin, chosen as reference compounds, in six distinct cancer cell
      lines. Compound 1 displayed less activity than 2. Computer-assisted phase
      contrast microscopy-related analysis revealed that 2 displayed cytostatic, not
      cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer
      apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells
      in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis
      further confirmed that 2 does not induce apoptotic features in U373 or A549
      cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives
      for anticancer cytostatic compounds can be derived.

PMID- 22976483
TI  - A modified side-to-end lymphaticovenular anastomosis.
AB  - BACKGROUND: Lymphaticovenular anastomosis (LVA) is a useful treatment for
      compression-refractory lymphedema with its effectiveness and minimal
      invasiveness. However, LVA requires supermicrosurgery, where lymphatic vessels
      with a diameter of 0.5 mm or smaller are anastomosed using 11-0 or 12-0 suture.
      To make LVA easier and safer, we adopted a modified side-to-end (S-E) anastomosis
      in LVA surgery. METHODS: We performed modified S-E LVAs in 14 limbs of female
      patients with lower extremity lymphedema (LEL). In modified S-E LVA, lateral
      windows with a length of 1.0 mm or longer were created on a lymphatic vessel and
      a vein, respectively, and side-to-side (S-S) anastomosis was established with 10
      0 continuous suture. After completion of S-S anastomosis, the vein distal to the
      anastomosis site was ligated to prevent venous backflow and subsequent thrombosis
      at the anastomosis site. Lymphedematous volume was evaluated preoperatively and
      at postoperative 6 months using LEL index. RESULTS: All the 24 modified S-E
      anastomoses could be completed without difficulty or revision for anastomosis,
      and showed good patency after completion of anastomosis. Postoperatively, LEL
      indices significantly decreased compared with preoperative LEL index (255.9 +/-
      14.1 vs. 274.9 +/- 22.2, P < 0.001). CONCLUSIONS: Modified S-E LVA can
      efficaciously divert lymph flows into venous circulation without performing
      supermicrosurgical anastomosis.

PMID- 22976484
TI  - An integrated image analysis platform to quantify signal transduction in single
      cells.
AB  - Microscopy can provide invaluable information about biological processes at the
      single cell level. It remains a challenge, however, to extract quantitative
      information from these types of datasets. We have developed an image analysis
      platform named YeastQuant to simplify data extraction by offering an integrated
      method to turn time-lapse movies into single cell measurements. This platform is
      based on a database with a graphical user interface where the users can describe
      their experiments. The database is connected to the engineering software Matlab,
      which allows extracting the desired information by automatically segmenting and
      quantifying the microscopy images. We implemented three different segmentation
      methods that recognize individual cells under different conditions, and
      integrated image analysis protocols that allow measuring and analyzing distinct
      cellular readouts. To illustrate the power and versatility of YeastQuant, we
      investigated dynamic signal transduction processes in yeast. First, we quantified
      the expression of fluorescent reporters induced by osmotic stress to study noise
      in gene expression. Second, we analyzed the dynamic relocation of endogenous
      proteins from the cytoplasm to the cell nucleus, which provides a fast measure of
      pathway activity. These examples demonstrate that YeastQuant provides a versatile
      and expandable database and an experimental framework that improves image
      analysis and quantification of diverse microscopy-based readouts. Such dynamic
      single cell measurements are highly needed to establish mathematical models of
      signal transduction pathways.

PMID- 22976485
TI  - Bacterial physiology: A Fab(H) way of controlling size for E. coli.

PMID- 22976486
TI  - Bacterial pathogenicity: A competent escape for Listeria.

PMID- 22976492
TI  - Rapid and sharp decline in HCV upon monotherapy with NS3 protease inhibitor, ACH
      1625.
AB  - BACKGROUND: ACH-1625 is a linear peptidomimetic inhibitor that non-covalently
      binds to HCV NS3 protease with high potency and specificity. Short-term
      monotherapy of HCV genotype-1 infection with ACH-1625 was found to be safe and
      resulted in >=3.3 log(10) IU/ml mean viral load reduction. These viral load decay
      data were analysed to compare HCV dynamics with prior reports and estimate the
      antiviral efficiency of ACH-1625. METHODS: Drug efficiency was estimated by
      analysing the viral decay following initiation of up to 5 days of monotherapy
      with ACH-1625 in 36 chronically infected HCV genotype-1 patients. During this
      monotherapy study, ACH-1625 was administered either twice-a-day for 4.5 days or
      once daily for 5 days at 5 different dose levels in 36 patients. RESULTS: A sharp
      viral decay during the first 48 h following the initiation of ACH-1625 treatment
      afforded high drug efficiency estimates (>=0.9934). In addition, an increase in
      the estimated drug efficiency was observed with increasing ACH-1625 dose. The
      observed anti-HCV response was fairly uniform in this proof-of-concept study
      across the population of 36 patients. CONCLUSIONS: Estimates of the treatment
      independent viral kinetics parameters were consistent with prior reports and the
      estimated drug efficiency of ACH-1625 monotherapy was very high (>=0.9934) in
      fasted and fed states.

PMID- 22976491
TI  - Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal
      inputs.
AB  - Heat shock protein 90 (HSP90) is an essential, abundant and ubiquitous eukaryotic
      chaperone that has crucial roles in protein folding and modulates the activities
      of key regulators. The fungal Hsp90 interactome, which includes numerous client
      proteins such as receptors, protein kinases and transcription factors, displays a
      surprisingly high degree of plasticity that depends on environmental conditions.
      Furthermore, although fungal Hsp90 levels increase following environmental
      challenges, Hsp90 activity is tightly controlled via post-translational
      regulation and an autoregulatory loop involving heat shock transcription factor 1
      (Hsf1). In this Review, we discuss the roles and regulation of fungal Hsp90. We
      propose that Hsp90 acts as a biological transistor that modulates the activity of
      fungal signalling networks in response to environmental cues via this Hsf1-Hsp90
      autoregulatory loop.

PMID- 22976493
TI  - Innovations in technology: social media and mobile technology in the care of
      adolescents with asthma.
AB  - This literature review analyzed technological interventions in the adolescent
      asthmatic population. A PubMed search was performed with terms of asthma,
      adolescents, social media, Internet, website, mobile phone, text messaging, SMS,
      Facebook, Twitter, MySpace, and Technology during a 2.5-year period and
      identified 64 abstracts. Three studies fulfilled the criteria for adolescent
      intervention using Internet-based sites but did not provide evidence for
      effectiveness. Two studies focused on mobile technology. One study included text
      message reminders for controller medication use in asthma patients. Perceived
      usefulness, satisfaction, and ease of use of text messages were high, but there
      was no improvement in asthma control. The literature search did not find any
      studies exploring the use of smartphone applications or social media services.
      Current studies of technology use in adolescents with asthma do not provide
      consistent evidence of effectiveness. The positive attitude toward use of social
      media or mobile technology opens the possibility for future studies to further
      explore the potential benefits of such interventions.

PMID- 22976494
TI  - Neutralizing antibodies are associated with a reduction of interferon-beta
      efficacy during the treatment of Japanese multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating
      disease of the central nervous system.  Interferon-beta (IFN-beta) has been used
      as the first line therapy for MS treatment in Japan, but patients treated with
      IFN-beta may develop antibodies, known as neutralizing antibodies (NAbs), which
      abrogate its therapeutic effects.  Intramuscular IFN-beta 1a and subcutaneous IFN
      beta 1b are currently available in Japan, but large-scale studies evaluating the
      prevalence and clinical implications of NAbs against these IFN-beta preparations
      in MS patients have only been performed in Caucasian populations.  NAbs
      positivity has been reported to be associated with HLA-DRB1 alleles, suggesting
      that the positivity might differ among populations with distinct genetic
      backgrounds.  Clinical information and sera were collected from 229 consecutive
      MS patients treated with IFN-beta in 4 centers in Japan.  Sera were tested for
      NAbs using a luciferase reporter gene assay.  In total, 5.2% of IFN-beta-1a
      treated patients (4/77) and 30.3% of IFN-beta-1b-treated patients (46/152) were
      positive for Nabs.  The frequency of NAbs was highest in patients treated for 13
      to 24 months.  Clinical relapse and contrast-enhancing lesions in the magnetic
      resonance imaging increased together with NAbs titers in this group.  In
      conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in
      Caucasian populations and is associated with an increase in disease activity. 
      Therefore, routine NAbs testing is recommended also in Asian populations to
      ensure the early identification of patients who would benefit from a change in
      therapy.

PMID- 22976495
TI  - Expression of the c-Met proto-oncogene and Integrin alpha5beta1 in human gastric
      cardia adenocarcinoma.
AB  - The hepatocyte growth factor receptor c-Met, a receptor tyrosine kinase, and
      Integrin alpha5beta1, one of the main ECM receptors of hepatocytes have been
      reported to play important roles in tumor growth by activating mitogenic
      signaling pathways. In human gastric cardia adenocarcinoma, however, expression
      of the c-Met and Integrin alpha5beta1 have not been reported. Here we examined
      the mRNA levels and protein expressions of these two genes and their relationship
      in human normal gastric cardia mucosa and primary carcinomas. Quantitative real
      time PCR was used to analyze the mRNA expression of both c-Met and Integrin
      alpha5beta1. The relationship between c-Met and Integrin alpha5beta1 expression
      and the histologic characteristics of tumors were studied. Western blot analysis
      was performed to investigate the presence of c-Met and Integrin alpha5beta1. The
      expression patterns of c-Met and Integrin alpha5beta1 in 45 frozen slides of
      cardia adenocarcinoma were identified by immunohistochemistry. Our results
      indicate that the expression of c-Met and of Integrin alpha5beta1 was
      significantly associated with tumor differentiation, TNM, and metastasis via the
      lymphogenic route. A significant positive correlation was also found between c
      Met and Integrin alpha5beta1 mRNA expression, suggesting that expression of c-Met
      and Integrin alpha5beta1 has mechanical significance in the early stages of human
      gastric cardia adenocarcinoma.

PMID- 22976496
TI  - Analysis of treatment failures and survival of patients with uterine papillary
      serous carcinoma: a Cooperation Task Force (CTF) Study.
AB  - OBJECTIVE: To assess the pattern of failures and the survival of patients with
      uterine papillary serous carcinoma (UPSC). METHODS: The hospital records of 119
      women with UPSC were reviewed. Surgery was the initial therapy for all the cases.
      The median follow-up of survivors was 133 months (range, 3-216 months). RESULTS:
      Postoperative treatment was used in 98 patients (82.4%). Adjuvant treatment was
      radiotherapy in 25 women, chemotherapy in 61 women, and chemotherapy plus
      radiotherapy in 12 women. Tumor recurred in 44 (37.0%) of the 119 patients, after
      a median time of 15.1 months. Relapse was symptomatic in 15 patients (34.1%), and
      recurrent disease involved peritoneum or distant sites in 26 (66.7%) of the 39
      patients for whom the site of failure was known. Five- and 10-year survival rates
      were 61.8% and 54.6%, respectively. Survival was related to disease stage (P <
      0.0001). Among patients with advanced tumor, 5-year survival was lower in women
      who had macroscopic residual disease after surgery than in those who had not
      (15.4% vs 37.5%; P = 0.08). Distant failures were higher in women with
      histologically proven positive nodes than in those with negative nodes (28.6% vs
      9.1%; P = 0.048). There was a trend to better survival for patients with stage I
      to stage II disease who underwent chemotherapy when compared with those who did
      not. CONCLUSIONS: Uterine papillary serous carcinoma has an aggressive clinical
      behavior with a great tendency to recur especially in peritoneal and distant
      sites. Tumor stage is a strong prognostic factor, whereas the role of adjuvant
      treatment is still uncertain.

PMID- 22976497
TI  - Comparison of the prognoses of FIGO stage I to stage II adenosquamous carcinoma
      and adenocarcinoma of the uterine cervix treated with radical hysterectomy.
AB  - OBJECTIVES: To evaluate the significance of adenosquamous carcinoma (ASC)
      compared with adenocarcinoma (AC) in the survival of surgically treated early
      stage cervical cancer. METHODS: We retrospectively reviewed the medical records
      of 163 patients with International Federation of Gynecology and Obstetrics stage
      IA2 to stage IIB cervical cancer who had been treated with radical hysterectomy
      with or without adjuvant radiotherapy between January 1998 and December 2008. The
      patients were classified according to the following: (1) histological subtype
      (ASC group or AC group) and (2) pathological risk factors (low-risk or
      intermediate/high-risk group). Survival was evaluated using the Kaplan-Meier
      method and compared using the log-rank test. Multivariate analysis of progression
      free survival (PFS) was performed using the Cox proportional hazards regression
      model to investigate the prognostic significance of histological subtype.
      RESULTS: Clinicopathological characteristics were similar between the ASC and AC
      histology groups. Patients with the ASC histology displayed a PFS rate similar to
      that of the patients with the AC histology in both the low-risk and
      intermediate/high-risk groups. Neither the recurrence rate nor the pattern of
      recurrence differed between the ASC group and the AC group. Univariate analysis
      revealed that patients with pelvic lymph node metastasis and parametrial invasion
      achieved significantly shorter PFS than those without these risk factors.
      CONCLUSIONS: Characteristics of the patients and the tumors as well as survival
      outcomes of ASC were comparable to adenocarcinoma of early-stage uterine cervix
      treated with radical hysterectomy. Our results in part support that the
      management of ASC could be the same as the one of AC of the uterine cervix.

PMID- 22976498
TI  - Loss of ARID1A expression is an early molecular event in tumor progression from
      ovarian endometriotic cyst to clear cell and endometrioid carcinoma.
AB  - OBJECTIVES: ARID1A is a recently identified tumor suppressor participating in
      chromatin remodeling. Somatic inactivating mutations of ARID1A and loss of its
      expression occur frequently in ovarian clear cell and endometrioid carcinomas and
      in uterine endometrioid carcinomas. Because endometriotic epithelium is thought
      to be the cell of origin of most ovarian clear cell and endometrioid carcinomas,
      we undertook an analysis of ARID1A expression of these tumors arising within an
      endometriotic cyst (endometrioma). MATERIALS AND METHODS: Our immunohistochemical
      study set consisted of 47 endometriotic cysts containing clear cell carcinoma in
      24 cases, well-differentiated ovarian endometrioid carcinoma in 20 cases, and
      mixed clear cell and endometrioid carcinoma in 3 cases. RESULTS: ARID1A loss was
      observed in 31 (66%) of 47 carcinomas; and therefore, these cases were
      informative for determining the temporal sequence of loss of ARID1A expression in
      tumor progression. In 16 of the 47 cases, ARID1A immunoreactivity was retained in
      both the endometriotic cyst and the carcinoma; and thus, these cases were not
      informative. All of the 31 informative cases showed loss of ARID1A
      immunoreactivity in the carcinoma and in the endometriotic cyst epithelium in
      direct continuity with the carcinoma but not in the cyst epithelium that was not
      adjacent to the tumor. CONCLUSIONS: Loss of ARID1A function as shown by loss of
      expression, presumably due to mutations, is an early molecular event in the
      development of most ovarian clear cell and endometrioid carcinomas arising in
      endometriomas.

PMID- 22976500
TI  - Preoperative FDG PET/CT in breast cancer patients: where are we going?

PMID- 22976499
TI  - Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I
      FP-CIT SPECT study.
AB  - PURPOSE: Psychiatric symptoms frequently occur in patients with movement
      disorders. They are not a mere reaction to chronic disability, but most likely
      due to a combination of psychosocial factors and biochemical dysfunction
      underlying the movement disorder. We assessed dopamine transporter (DAT)
      availability by means of (123)I-FP-CIT SPECT, and motor and psychiatric features
      in patients with Parkinson's disease, primary dystonia and essential tremor,
      exploring the association between SPECT findings and symptom severity. METHODS:
      Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with
      primary dystonia and 15 patients with essential tremor. The severity of
      depression symptoms was assessed using the Hamilton depression rating scale,
      anxiety levels using the Hamilton anxiety rating scale and hedonic tone
      impairment using the Snaith-Hamilton pleasure scale. Specific (123)I-FP-CIT
      binding in the caudate and putamen was calculated based on ROI analysis. The
      control group included 17 healthy subjects. RESULTS: As expected, DAT
      availability was significantly decreased in patients with Parkinson's disease,
      whereas in essential tremor and dystonia patients it did not differ from that
      observed in the control group. In Parkinson's disease patients, an inverse
      correlation between severity of depression symptoms and DAT availability in the
      left caudate was found (r = -0.63, p = 0.002). In essential tremor patients,
      levels of anxiety symptoms were inversely correlated with DAT availability in the
      left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both
      anxiety and depression symptoms were inversely associated with DAT availability
      in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002,
      respectively). There were no correlations between psychometric scores and (123)I
      FP-CIT uptake ratios in healthy subjects. CONCLUSION: We found association
      between presynaptic dopaminergic function and affective symptoms in different
      movement disorders. Interestingly, the inverse correlation was present in each
      group of patients, supporting the fascinating perspective that common subcortical
      substrates may be involved in both anxiety and depression dimensions and movement
      disorders.

PMID- 22976502
TI  - Proton therapy: decisions, decisions.

PMID- 22976501
TI  - Arthroscopic management of anterior shoulder instability with glenoid bone
      defects.
AB  - Bony deficiency of the anterior glenoid rim may significantly contribute to
      recurrent shoulder instability. Today, based on clinical and biomechanical data,
      a bony reconstruction is recommended in patients with bone loss of greater than
      20-25 % of the glenoid surface area. Recent advances in arthroscopic instruments
      and techniques presently allow minimally invasive and arthroscopic reconstruction
      of glenoid bone defects and osteosynthesis of glenoid fractures. This article
      underlines the role of glenoid bone deficiency in recurrent shoulder instability,
      provides an update on the current management regarding this pathology and
      highlights the modern techniques for surgical treatment. Therefore, it can help
      orthopaedic surgeons in the treatment and decision-making when dealing with these
      difficult to treat patients in daily clinical practice.

PMID- 22976504
TI  - Using Healthcare Failure Mode and Effect Analysis to reduce medication errors in
      the process of drug prescription, validation and dispensing in hospitalised
      patients.
AB  - OBJECTIVES: To identify actions to reduce medication errors in the process of
      drug prescription, validation and dispensing, and to evaluate the impact of their
      implementation. METHODS: A Health Care Failure Mode and Effect Analysis (HFMEA)
      was supported by a before-and-after medication error study to measure the actual
      impact on error rate after the implementation of corrective actions in the
      process of drug prescription, validation and dispensing in wards equipped with
      computerised physician order entry (CPOE) and unit-dose distribution system (788
      beds out of 1080) in a Spanish university hospital. The error study was carried
      out by two observers who reviewed medication orders on a daily basis to register
      prescription errors by physicians and validation errors by pharmacists. Drugs
      dispensed in the unit-dose trolleys were reviewed for dispensing errors. Error
      rates were expressed as the number of errors for each process divided by the
      total opportunities for error in that process times 100. RESULTS: A reduction in
      prescription errors was achieved by providing training for prescribers on CPOE,
      updating prescription procedures, improving clinical decision support and
      automating the software connection to the hospital census (relative risk
      reduction (RRR), 22.0%; 95% CI 12.1% to 31.8%). Validation errors were reduced
      after optimising time spent in educating pharmacy residents on patient safety,
      developing standardised validation procedures and improving aspects of the
      software's database (RRR, 19.4%; 95% CI 2.3% to 36.5%). Two actions reduced
      dispensing errors: reorganising the process of filling trolleys and drawing up a
      protocol for drug pharmacy checking before delivery (RRR, 38.5%; 95% CI 14.1% to
      62.9%). CONCLUSIONS: HFMEA facilitated the identification of actions aimed at
      reducing medication errors in a healthcare setting, as the implementation of
      several of these led to a reduction in errors in the process of drug
      prescription, validation and dispensing.

PMID- 22976503
TI  - Microwell devices with finger-like channels for long-term imaging of HIV-1
      expression kinetics in primary human lymphocytes.
AB  - A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)
      is a sub-population of latently infected CD4(+) T lymphocytes. The cellular and
      viral mechanisms regulating HIV-1 latency are not completely understood, and a
      promising technique for probing the regulation of HIV-1 latency is single-cell
      time-lapse microscopy. Unfortunately, CD4(+) T lymphocytes rapidly migrate on
      substrates and spontaneously detach, making them exceedingly difficult to track,
      hampering single-cell level studies. To overcome these problems, we built
      microdevices with a three-level architecture. The devices contain arrays of
      finger-like microchannels to "corral" T-lymphocyte migration, round wells that
      are accessible to pipetting, and microwells connecting the microchannels with the
      round wells. T lymphocytes that are loaded into a well first settle into the
      microwells and then to microchannels by gravity. Within the microchannels, T
      lymphocytes are in favorable culture conditions because they are in physical
      contact with each other, under no mechanical stress, and fed from a large
      reservoir of fresh medium. Most importantly, T lymphocytes in the microchannels
      are not exposed to any flow and their random migration is restricted to a nearly
      one-dimensional region, greatly facilitating long-term tracking of multiple cells
      in time-lapse microscopy. The devices have up to nine separate round wells,
      making it possible to test up to nine different cell lines or medium conditions
      in a single experiment. Activated primary CD4(+) T lymphocytes, resting primary
      CD4(+) T lymphocytes, and THP-1 monocytic leukemia cells loaded into the devices
      maintained viability over multiple days. The devices were used to track the
      fluorescence level of individual primary CD4(+) T lymphocytes expressing green
      fluorescent protein (GFP) for up to 60 hours (h) and to quantify single-cell gene
      expression kinetics of four different HIV-1 variants. The kinetics of GFP
      expression from the lentiviruses in the primary CD4(+) T lymphocytes agree with
      previous measurements of these lentiviral vectors in the immortalized Jurkat T
      lymphocyte cell line. The proposed devices offer a simple, robust approach to
      long-term single-cell studies of environmentally sensitive primary lymphocytes.

PMID- 22976506
TI  - Organocatalytic activation of polycyclic aromatic compounds for asymmetric Diels
      Alder reactions.

PMID- 22976505
TI  - Evaluation of a predevelopment service delivery intervention: an application to
      improve clinical handovers.
AB  - BACKGROUND: We developed a method to estimate the expected cost-effectiveness of
      a service intervention at the design stage and 'road-tested' the method on an
      intervention to improve patient handover of care between hospital and community.
      METHOD: The development of a nine-step evaluation framework: 1. Identification of
      multiple endpoints and arranging them into manageable groups; 2. Estimation of
      baseline overall and preventable risk; 3. Bayesian elicitation of expected
      effectiveness of the planned intervention; 4. Assigning utilities to groups of
      endpoints; 5. Costing the intervention; 6. Estimating health service costs
      associated with preventable adverse events; 7. Calculating health benefits; 8.
      Cost-effectiveness calculation; 9. Sensitivity and headroom analysis. RESULTS:
      Literature review suggested that adverse events follow 19% of patient discharges,
      and that one-third are preventable by improved handover (ie, 6.3% of all
      discharges). The intervention to improve handover would reduce the incidence of
      adverse events by 21% (ie, from 6.3% to 4.7%) according to the elicitation
      exercise. Potentially preventable adverse events were classified by severity and
      duration. Utilities were assigned to each category of adverse event. The costs
      associated with each category of event were obtained from the literature. The
      unit cost of the intervention was ?16.6, which would yield a Quality Adjusted
      Life Year (QALY) gain per discharge of 0.010. The resulting cost saving was ?14.3
      per discharge. The intervention is cost-effective at approximately ?214 per QALY
      under the base case, and remains cost-effective while the effectiveness is
      greater than 1.6%. CONCLUSIONS: We offer a usable framework to assist in ex ante
      health economic evaluations of health service interventions.

PMID- 22976507
TI  - A randomized controlled trial of interventions to promote adjustment in children
      with congenital heart disease entering school and their families.
AB  - OBJECTIVE: To report on a randomized controlled trial of psychological
      interventions to promote adjustment in children with congenital heart disease and
      their families. METHOD: Following baseline assessment, 90 children (aged 4-5
      years) and their families were randomly assigned to an Intervention or Control
      group before entering school. 68 (76%) were retained at 10-month follow-up.
      RESULTS: Gains were observed on measures of maternal mental health and family
      functioning. Although no differences were found on measures of child behavior at
      home or school, children in the intervention group were perceived as "sick" less
      often by their mother and missed fewer days from school. A regression model,
      using baseline measures as predictors, highlighted the importance of maternal
      mental health, worry and child neurodevelopmental functioning for child
      behavioral outcomes almost a year later. CONCLUSIONS: The intervention promoted
      clinically significant gains for the child and family. The program is of
      generalizable significance.

PMID- 22976508
TI  - Self-management, satisfaction with family functioning, and the course of
      psychological symptoms in emerging adults with spina bifida.
AB  - OBJECTIVE: To explore psychological symptoms in emerging adults with spina bifida
      (SB) and their association with self-management and satisfaction with family
      functioning. METHODS: Longitudinal data were collected at 2 time points, 15
      months apart, in 48 individuals with SB. Reliable change indices and paired
      samples t-tests assessed change in anxiety and depressive symptoms. Hierarchical
      regression models explored the contributions of SB severity, family satisfaction,
      and self-management in explaining change in psychological symptoms. RESULTS: No
      significant group level differences in psychological symptoms were found across
      time in participants (Mean age 22 years), but significant individual-level change
      in anxiety symptoms (n = 13) and depressive symptoms (n = 9) was observed.
      Improved satisfaction with family functioning was associated with decreased
      anxiety symptoms (b = -0.30, p = .02), and increased SB self-management was
      related to reduced depressive symptoms (b = -0.63, p = .01). CONCLUSIONS: Changes
      in self-management and satisfaction with family functioning may influence the
      course of psychological symptoms.

PMID- 22976510
TI  - An exceptional post-traumatic double hernia.

PMID- 22976509
TI  - Impaired health-related quality of life in preschoolers with obesity.
AB  - OBJECTIVES: To examine whether health-related quality of life (HRQOL) for
      treatment-seeking preschoolers with obesity (N = 60) differed from preschoolers
      in a nonclinical comparison sample (N = 457). METHODS: Parents in both samples
      completed the parent-proxy form of the pediatric quality of life inventory
      (PedsQL). Between-group comparisons were conducted to examine differences for all
      scales and summary scores of the PedsQL. RESULTS: Parent proxy-reported HRQOL was
      significantly lower for treatment-seeking preschoolers with obesity for all
      scales and summary scores except school functioning. Differences on the total
      scale score met the criterion for being a clinically important difference.
      CONCLUSIONS: Our study suggests treatment-seeking families perceive worse HRQOL
      for children with obesity as early as the preschool years. Discussion of HRQOL
      may be a more effective strategy for health care professionals in broaching the
      topic of weight with parents and identifying families who may be more receptive
      to weight management suggestions for preschoolers.

PMID- 22976511
TI  - Atomic dopants involved in the structural evolution of thermally graphitized
      graphene.
AB  - Thermally doped nitrogen atoms on the sp(2)-carbon network of reduced graphene
      oxide (rGO) enhance its electrical conductivity. Atomic structural information of
      thermally annealed graphene oxide (GO) provides an understanding on how the
      heteroatomic doping could affect electronic property of rGO. Herein, the
      spectroscopic and microscopic variations during thermal graphitization from 573
      to 1,373 K are reported in two different rGO sheets, prepared by thermal
      annealing of GO (rGO(therm)) and post-thermal annealing of chemically nitrogen
      doped rGO (post-therm-rGO(N(2)H(4))). The spectroscopic transitions of
      rGO(N(2)H(4)) in thermal annealing ultimately showed new oxygen-functional
      groups, such as cyclic edge ethers and new graphitized nitrogen atoms at 1,373 K.
      During the graphitization process, the microscopic evolution resolved by scanning
      tunneling microscopy (STM) produced more wrinkled surface morphology with
      graphitized nanocrystalline domains due to atomic doping of nitrogen on a post
      therm-rGO(N(2)H(4)) sheet. As a result, the post-therm-rGO(N(2)H(4))-containing
      nitrogen showed a less defected sp(2)-carbon network, resulting in enhanced
      conductivity, whereas the rGO(therm) sheet containing no nitrogen had large
      topological defects on the basal plane of the sp(2)-carbon network. Thus, our
      investigation of the structural evolution of original wrinkles on a GO sheet
      incorporated into the graphitized N-doped rGO helps to explain how the atomic
      doping can enhance the electrical conductivity.

PMID- 22976512
TI  - Requirements for the nuclear entry of polyplexes and nanoparticles during
      mitosis.
AB  - BACKGROUND: Nonviral gene delivery has a limited efficacy partly as a result of
      poor nuclear delivery, yet an understanding of the mechanisms of nuclear entry is
      limited. The present study aimed to test the common hypothesis that most nonviral
      vehicles enter the nucleus during cell division. METHODS: Polystyrene particles
      with diameters of 24-200 nm and carboxylate or amine surface groups, were either
      used as is or, alternatively, were functionalized with carboxyl-, hydroxyl- or
      amine- terminated poly(ethylene glycol) (PEG) and subsequently microinjected into
      the cytoplasm of NIH/3T3 mouse fibroblast cells. The post-mitotic locations of
      the particles were analyzed and compared with the locations of cytoplasmically
      microinjected plasmid DNA (pDNA), pDNA polyplexes or nuclear localization signal
      (NLS)-functionalized pDNA polyplexes. RESULTS: We observed that all polystyrene
      particles as well as the NLS-free polyplexes were excluded from the nucleus post
      mitosis. By contrast, free pDNA and pDNA polyplexes containing an NLS accumulated
      in the nucleus after division. CONCLUSIONS: These data suggest that biochemically
      specific modes of association with chromatin-associated proteins or other nuclear
      components are necessary for the nuclear inclusion of polyplexes and
      nanoparticles during mitosis.

PMID- 22976513
TI  - Diagnosing oral lichenoid contact reaction: clinical judgment versus skin-patch
      test.
AB  - AIM: Objective of this study was to compare the skin-patch test with the clinical
      diagnosis of oral lichenoid contact reaction (OLCR) as indicators for amalgam
      replacement. METHODS: Of 53 patients (38 female and 15 male; mean age 48.7) with
      oral lichen planus (OLP), 26 were identified as having OLCR, and clinically
      graded according to the proximity of their lesions with amalgam fillings: class I
      (weak association), class II (moderate association), and class III (strong
      association). All OLCR patients were skin-patch tested for both standard
      (Brazilian) and specific allergens (TROLAB, Germany). Patients were considered
      skin-patch positive only if they developed positive skin reactions for thimerosal
      and/or amalgam components. Amalgam replacement was indicated in all class II and
      III patients. For class-I patients, amalgam replacement was indicated only if
      they were skin-patch test positive. Readings for the skin-patch test were made at
      48h and 96h. RESULTS: Of the 26 patients with OLCR, two missed the follow-up and
      were excluded, leaving 24 cases. Of these, four were class-I, and all were
      negative for the skin-patch test. Twelve were class-II, of whom seven were skin
      patch positive. Eight were class-III, of whom six were skin-patch positive.
      Following amalgam replacement in the 12 class-II patients, six showed improvement
      and six had complete resolution, while in the eight class-III patients, two
      showed improvement and six a complete resolution. CONCLUSION: Clinical diagnosis
      of OLCR lesions is a more reliable indicator for the question of amalgam
      replacement than is the skin-patch test.

PMID- 22976514
TI  - The effect of low level laser therapy on pain reduction after third molar
      surgery.
AB  - AIM: The aim of this study was to evaluate the effects of low level laser on the
      postoperative pain of patients who had to undergo third molar surgery. METHODS:
      In a randomized clinical setting, 100 patients were assigned to two groups of 50
      in each. Every patient underwent surgical removal of one mandibular third molar
      (with osteotomy). After suturing the flap, the soft laser was applied to every
      patient. In group I laser radiation was applied by the dental assistant with
      output power of 100 mW, in continuous mode with sweeping motion, in group II, the
      laser hand piece was only brought into position without releasing energy, so that
      no patient knew which group he belonged to. The patient was given a pain
      evaluation form where they could determine their individual pain level and
      duration. RESULTS: The statistical tests showed significant difference in pain
      level between laser and control group (P<0.001) but no significant difference
      found in pain duration in two groups (P=0.019). CONCLUSION: The result of this
      study verifies the positive effect of the soft-laser therapy in the postoperative
      complication after third molar extraction.

PMID- 22976515
TI  - Identification of postmenopausal women at risk of osteoporosis using panoramic
      and intraoral radiographs- a review.
AB  - Osteoporosis is one of the most common human bone diseases affecting millions of
      people, including over one-third of females above the age of 65. Osteoporosis is
      characterized by decreased bone density and weakened bones. There is evidence
      that osteoporosis affects the craniofacial and oral structures, although the
      contribution of osteoporosis in the loss of periodontal attachments, teeth, and
      height of the residual ridge has not been clearly elucidated. Therefore, the
      relationship between systemic osteoporosis and oral health is still a complex
      problem of great interest to a large number of researchers and clinicians. In
      addition, the dentist could screen patients with unrecognized osteoporosis using
      information already available in the dental office. The purpose of screening is
      to identify individuals who are likely to benefit from treatment. The fact that
      dental radiographs are regularly made on a large fraction of the adult population
      makes their potential use as a marker of skeletal health an exciting avenue of
      research. The purpose of this article was to review the use of various intraoral
      as well as panoramic radiographs to promote early identification of patients at
      risk for osteoporosis.

PMID- 22976516
TI  - Management of temporomandibular joint ankylosis: a case report of joint
      replacement with piezoelectric surgery.
AB  - AIM: Temporomandibular joint (TMJ) ankylosis is a joint disorder which refers to
      bone or fibrous adhesion of the anatomic joint components and the ensuing loss of
      function. This report describes the management of a case of bilateral TMJ
      ankylosis in a 20-year-old patient with prosthetic replacement with the aid of a
      piezoelectric instrument (MECTRON (R). METHODS: The right ankylotic mass was
      surgically removed and replaced by a custom-made prosthesis based on data
      obtained from three-dimensional computed tomography (CT) reconstruction of the
      skull of the patient using a stereolithography model. RESULTS: At six months
      postoperative, the opening of the mouth was stable at 36 mm and imaging studies
      (CT and magnetic resonance imaging [MRI]) showed a great condylar prosthesis and
      surrounding tissues in addition to partial remodeling of the left TMJ.
      CONCLUSION: In this patient, despite the bilateral ankylosis, it was sufficient
      to intervene only on the right TMJ, which presented a serious bone block, with
      mobilization since surgery gradually restored the anatomical and functional
      conditions of the left TMJ compatible with normal activities of mastication and
      speech.

PMID- 22976517
TI  - Local anesthesia needle breakage in a 5-year-old child during inferior alveolar
      nerve block with the Vazirani-Akinosi technique.
AB  - Breakage of a local anesthetic needle in dentistry is a rare but potentially
      serious event. Here we describe a case of breakage of a hypodermic needle during
      administration of local anesthesia with a Vazirani-Akinosi mandibular nerve block
      in a 5-year-old uncooperative patient under moderate sedation with midazolam. The
      needle was localized using a fluoroscopy device and then removed under general
      anaesthesia. The postoperative course was unremarkable, without any neurological
      or vascular deficits.

PMID- 22976518
TI  - Esthetics in the edentulous: clinical steps for recovering of maxillary anterior
      teeth harmony.
AB  - Smile designing for edentulous patients has not been much investigated; the
      selection of artificial teeth is a task that follows multiple consequential steps
      such as choosing their form, size, material, color and disposition. Even if smile
      designing is thought to involve some artistic abilities, specific techniques or
      suggestions have been proposed in the literature to perform each step of the
      selection of artificial teeth, keeping in mind the importance of consultation and
      understanding of the patient preferences. This article will focus on the
      recovering of maxillary anterior teeth harmony in an edentulous patient; a
      clinical case report will show the rationale process of anterior teeth selection,
      supported by scientific guidelines found in the literature.

PMID- 22976520
TI  - Determinants and survival implications of low bone mineral density in end-stage
      renal disease patients.
AB  - BACKGROUND: Reduced bone mineral density (BMD) is common in end-stage renal
      disease (ESRD) patients and predicts outcomes. The chronic kidney disease-mineral
      bone disorder contributes to low BMD in ESRD; however, the impact of classical
      risk factors for osteoporosis in the general population, such as body weight and
      fat mass, remains less well defined in ESRD subjects. METHODS: BMD, body
      composition (dual-energy X-ray absorptiometry), nutritional status (subjective
      global assessment), hand grip strength and multiple biomarkers were investigated
      in 361 patients (218 males; 60.4%) starting on dialysis. The relations between
      BMD, body composition and biomarkers were analyzed at baseline, and the impact of
      BMD on mortality was analyzed prospectively. RESULTS: In univariate analysis, T
      score correlated with fat mass (r = 0.308, p<0.001), lean body mass (r = 0.278,
      p<0.001), leptin (r = 0.124, p = 0.028) as well as the anabolic marker insulin
      like growth factor-1 (IGF-1; r = 0.301, p<0.001), and its binding proteins IGFBP
      1 (r = -0.342, p<0.001) and IGFBP-3 (0.231, p<0.001). BMD T-score was
      independently associated with age, total fat mass, intact parathyroid hormone and
      presence of wasting. During 5 years of follow-up, 87 deaths were recorded. Each
      unit of increase of T-score was associated with decreased all-cause mortality,
      which persisted after multivariate adjustment (hazard ratio = 0.824, 95%
      confidence interval, 0.681-0.996). CONCLUSIONS: BMD is associated with body
      composition, especially total fat mass, nutritional status and mortality risk in
      ESRD patients.

PMID- 22976519
TI  - Does maltreatment in childhood affect sexual orientation in adulthood?
AB  - Epidemiological studies find a positive association between physical and sexual
      abuse, neglect, and witnessing violence in childhood and same-sex sexuality in
      adulthood, but studies directly assessing the association between these diverse
      types of maltreatment and sexuality cannot disentangle the causal direction
      because the sequencing of maltreatment and emerging sexuality is difficult to
      ascertain. Nascent same-sex orientation may increase risk of maltreatment;
      alternatively, maltreatment may shape sexual orientation. Our study used
      instrumental variable models based on family characteristics that predict
      maltreatment but are not plausibly influenced by sexual orientation (e.g., having
      a stepparent) as natural experiments to investigate whether maltreatment might
      increase the likelihood of same-sex sexuality in a nationally representative
      sample (n = 34,653). In instrumental variable models, history of sexual abuse
      predicted increased prevalence of same-sex attraction by 2.0 percentage points
      [95 % confidence interval (CI) = 1.4-2.5], any same-sex partners by 1.4
      percentage points (95 % CI = 1.0-1.9), and same-sex identity by 0.7 percentage
      points (95 % CI = 0.4-0.9). Effects of sexual abuse on men's sexual orientation
      were substantially larger than on women's. Effects of non-sexual maltreatment
      were significant only for men and women's sexual identity and women's same-sex
      partners. While point estimates suggest much of the association between
      maltreatment and sexual orientation may be due to the effects of maltreatment on
      sexual orientation, confidence intervals were wide. Our results suggest that
      causal relationships driving the association between sexual orientation and
      childhood abuse may be bidirectional, may differ by type of abuse, and may differ
      by sex. Better understanding of this potentially complex causal structure is
      critical to developing targeted strategies to reduce sexual orientation
      disparities in exposure to abuse.

PMID- 22976521
TI  - Retention and growth of urinary stones: insights from imaging.
AB  - Recent work in nephrolithiasis has benefited from 2 special kinds of imaging:
      endoscopic study of patient kidneys with high-quality instruments, and
      examination of stones with microscopic computed tomography (micro CT). The
      combination of these has provided new evidence that there is more than 1
      mechanism by which stones are retained in the kidney until they achieve sizes to
      be clinically relevant. This review describes what is known about the formation
      of stones on Randall's plaque, the formation of stones on ductal plugs and the
      ways in which stones may grow in free solution within the calyceal or pelvic
      spaces. Studies of urolithiasis need to recognize that any group of "stone
      formers" likely includes patients who differ fundamentally regarding which
      mechanism of stone formation is the primary route for their stones. Separation of
      patients on the basis of which mechanism (or combination of mechanisms) underlies
      their disease will be important for advancing research in the area of
      urolithiasis.

PMID- 22976523
TI  - The role of the nephrologist in the care of geriatric patients.

PMID- 22976522
TI  - Acid-base pathophysiology after 130 years: confusing, irrational and
      controversial.
AB  - BACKGROUND: The interface between acid-base physiology and blood gas
      interpretation is historically both stimulating and turbulent. Since the
      pioneering work of many celebrated names in the history of acid-base disorders,
      such as Arrhenius, Henderson, Hasselbalch and many more to follow, substantial
      progress in acid-base knowledge has been made over the last 130 years. Out of the
      chaos of competing definitions, concepts and terms, many have tried to bring an
      orderly approach to acid-base balance. Nevertheless, the mechanisms responsible
      for acid-base balance are unfortunately still incompletely understood, and
      moreover, considerable controversy has developed over the past decade as to how
      to classify and understand acid-base derangements occurring as a result of
      abnormalities in acid-base balance. METHODS: Analysis of the medical literature,
      including a MEDLINE and EMBASE search, and a search of internal medicine,
      critical care and nephrology textbooks and reference lists, was performed on
      topics pertaining to the assessment and management of acid-base disorders,
      focusing on the gaps in our knowledge and on controversial issues. RESULTS:
      Several confusing, irrational and controversial issues concerning acid-base
      nomenclature, reference values, pathophysiology, assessment of acid-base
      disorders and therapy were found. CONCLUSIONS: Despite huge progress in acid-base
      knowledge, several confusing, irrational and controversial issues remain.
      Suggestions to reduce the confusion are provided.

PMID- 22976524
TI  - Vitamin D metabolism and activity as well as genetic variants of the vitamin D
      receptor (VDR) in chronic kidney disease patients.
AB  - For a long time, the role of vitamin D in chronic kidney disease (CKD) received
      less attention than treating vitamin D metabolism disorders. Low active vitamin D
      levels represent one of the most important factors in the pathophysiology of
      secondary hyperparathyroidism. For this reason, the administration of active
      vitamin D compounds is commenced during the course of CKD treatment. Moreover,
      patients with CKD exhibit a high prevalence of hypovitaminosis of 25
      hydroxyvitamin D (25[OH]D) unrelated to vitamin D intake. However, several
      studies have recently advanced our knowledge about the effects of both the
      25(OH)D and 1,25(OH)2D forms of endogenous vitamin D and the possible beneficial
      effects of vitamin D treatment. These studies add to the already well-known
      effects of vitamin D on mineral metabolism. Several studies have hypothesized a
      link between reduced levels of 25-OH D and a greater cardiovascular risk in the
      general population. Another important aspect of vitamin D metabolism is the
      existence of polymorphic genetic variants of the vitamin D receptors (VDRs). Most
      studies have aimed to determine whether VDR polymorphisms are involved in the
      development of secondary hyperparathyroidism (sHPT). 

PMID- 22976525
TI  - A spectroscopic assignment technique for membrane proteins reconstituted in
      magnetically aligned bicelles.
AB  - Oriented-sample NMR (OS-NMR) has emerged as a powerful tool for the structure
      determination of membrane proteins in their physiological environments. However,
      the traditional spectroscopic assignment method in OS NMR that uses the "shotgun"
      approach, though effective, is quite labor- and time-consuming as it is based on
      the preparation of multiple selectively labeled samples. Here we demonstrate
      that, by using a combination of the spin exchange under mismatched Hartmann-Hahn
      conditions and a recent sensitivity-enhancement REP-CP sequence, spectroscopic
      assignment of solid-state NMR spectra of Pf1 coat protein reconstituted in
      magnetically aligned bicelles can be significantly improved. This method yields a
      two-dimensional spin-exchanged version of the SAMPI4 spectrum correlating the
      (15)N chemical shift and (15)N-(1)H dipolar couplings, as well as spin
      correlations between the (i, i +/- 1) amide sites. Combining the spin-exchanged
      SAMPI4 spectrum with the original SAMPI4 experiment makes it possible to
      establish sequential assignments, and this technique is generally applicable to
      other uniaxially aligned membrane proteins. Inclusion of an (15)N-(15)N
      correlation spectrum into the assignment process helps establish correlations
      between the peaks in crowded or ambiguous spectral regions of the spin-exchanged
      SAMPI4 experiment. Notably, unlike the traditional method, only a uniformly
      labeled protein sample is required for spectroscopic assignment with perhaps only
      a few selectively labeled "seed" spectra. Simulations for the magnetization
      transfer between the dilute spins under mismatched Hartmann Hahn conditions for
      various B (1) fields have also been performed. The results adequately describe
      the optimal conditions for establishing the cross peaks, thus eliminating the
      need for lengthy experimental optimizations.

PMID- 22976526
TI  - Agglomerates of aberrant DNA methylation are associated with toxicant-induced
      malignant transformation.
AB  - Epigenetic dysfunction is a known contributor in carcinogenesis, and is emerging
      as a mechanism involved in toxicant-induced malignant transformation for
      environmental carcinogens such as arsenicals or cadmium. In addition to aberrant
      DNA methylation of single genes, another manifestation of epigenetic dysfunction
      in cancer is agglomerative DNA methylation, which can participate in long-range
      epigenetic silencing that targets many neighboring genes and has been shown to
      occur in several types of clinical cancers. Using in vitro model systems of
      toxicant-induced malignant transformation, we found hundreds of aberrant DNA
      methylation events that emerge during malignant transformation, some of which
      occur in an agglomerative fashion. In an arsenite-transformed prostate epithelial
      cell line, the protocadherin (PCDH), HOXC and HOXD gene family clusters are
      targeted for agglomerative DNA methylation. The agglomerative DNA methylation
      changes induced by arsenicals appear to be common and clinically relevant events,
      since they occur in other human cancer cell lines and models of malignant
      transformation, as well as clinical cancer specimens. Aberrant DNA methylation in
      general occurred more often within histone H3 lysine-27 trimethylation stem cell
      domains. We found a striking association between enrichment of histone H3 lysine
      9 trimethylation stem cell domains and toxicant-induced agglomerative DNA
      methylation, suggesting these epigenetic modifications may become aberrantly
      linked during malignant transformation. In summary, we found an association
      between toxicant-induced malignant transformation and agglomerative DNA
      methylation, which lends further support to the hypothesis that epigenetic
      dysfunction plays an important role in toxicant-induced malignant transformation.

PMID- 22976527
TI  - Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless
      of the presence of Merkel cell polyomavirus.
AB  - Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine
      origin. The recently found Merkel cell polyomavirus (MCV) integrates clonally in
      the tumour genome, which suggests an important role in the pathogenesis of the
      disease. Previous small-scale studies have detected anti-apoptotic protein bcl-2
      in 80 % of MCC tumours, but its correlation to the prognosis of MCC remains
      controversial. Our aim was to clarify the correlation of immunohistochemical
      expression of bcl-2 to MCV presence and MCC prognosis. We analyzed 116 primary
      MCC specimens with corresponding clinical data by immunohistochemistry for bcl-2.
      The presence of MCV DNA had been analyzed by quantitative PCR for 108 tumours.
      The correlations were analyzed statistically. Of the primary MCC samples, 85 %
      were bcl-2 positive. No significant differences in MCV DNA occurred between the
      bcl-2-positive and bcl-2-negative tumours. Local and systemic metastasis was more
      common in patients with bcl-2 negative tumours (33 %) than in patients with bcl-2
      positive tumours (12 %; p = 0.04) at the time of diagnosis. The mean overall
      survival was higher in patients with bcl-2-positive tumours than of those with
      negative tumours (mean survival 1,814 days (5.0 years) vs. 769 days (2.1 years),
      p = 0.01). Bcl-2 positivity indicates better clinical stage at the time of
      diagnosis and a longer survival in MCC.

PMID- 22976528
TI  - Efficacy of pegylated interferon-alpha treatment for 24 months in chronic delta
      hepatitis and predictors of response.
AB  - BACKGROUND: To determine the efficacy of pegylated interferon-alpha (PEG-IFN
      alpha) therapy for 24 months in chronic delta hepatitis (CDH). METHODS: Patients
      with CDH who were treated by PEG-IFN-alpha2a or -2b for 24 months were included
      in the study. Demographic, biochemical and virological parameters were recorded
      at baseline and during follow-up. All included patients completed a treatment
      period of 24 months and at least a 6 month (range 6-60) follow-up period.
      Biochemical and virological response rates at end of treatment and end of follow
      up were calculated, and predictors of sustained virological response (SVR) were
      analysed. RESULTS: In total, 32 patients (22 males; mean age +/- SD 42.7 +/- 12
      years) with CDH who were treated with PEG-IFN-alpha2a (180 ug) or -2b (1.5 ug/kg)
      once a week subcutaneously for 24 months were included in the study. All patients
      had compensated liver disease (25 [78%] were non-cirrhotic), increased
      transaminase levels and HDV RNA positivity at baseline. Genotypic analyses of HDV
      showed genotype I in all. Mean duration of follow-up was 19.5 months. At the end
      of treatment, virological response was achieved in 16 (50%) patients. SVR at the
      end of follow-up was achieved in 15 (47%) patients. A negative HDV RNA at 6
      months of treatment was the only predictor of SVR (OR = 20; 95% CI 2, 195; P =
      0.01). CONCLUSIONS: PEG-IFN-alpha treatment achieved SVR in approximately half of
      the patients with CDH, and relapse rate was very low during the follow-up.
      Negativity of HDV RNA at 6 months may predict SVR in CDH.

PMID- 22976529
TI  - Spanish translation and validation of four short pelvic floor disorders
      questionnaires.
AB  - INTRODUCTION AND HYPOTHESIS: Globally, Spanish is the primary language for 329
      million people; however, most urogynecologic questionnaires are available in
      English. We set out to develop valid Spanish translations of the Questionnaire
      for Urinary Incontinence Diagnosis (QUID), the Three Incontinence Questions
      (3IQ), and the short Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor
      Impact Questionnaire (PFIQ-7). METHODS: The TRAPD method (translation, review,
      adjudication, pretesting, and documentation) was used for translation. Eight
      native Spanish-speaking translators developed Spanish versions collaboratively.
      These were pretested with cognitive interviews and revised until optimal. For
      validation, bilingual patients at seven clinics completed Spanish and English
      questionnaire versions in randomized order. Participants completed a second set
      of questionnaires later. The Spanish versions' internal consistency and
      reliability and Spanish-English agreement were measured using Cronbach's alpha,
      weighted kappa, and intraclass correlation coefficients. RESULTS: A total of 78
      subjects were included; 94.9 % self-identified as Hispanic and 73.1 % spoke
      Spanish as their primary language. The proportion of per-item missing responses
      was similar in both languages (median 1.3 %). Internal consistency for Spanish
      PFDI-20 subscales was acceptable to good and for PFIQ-7 and QUID excellent. Test
      retest reliability per item was moderate to near perfect for PFDI-20, substantial
      to near perfect for PFIQ-7 and 3IQ, and substantial for QUID. Spanish-English
      agreement for individual items was substantial to near perfect for all
      questionnaires (kappa range 0.64-0.95) and agreement for PFDI-20, PFIQ-7, and
      QUID subscales scores was high [intraclass correlation coefficient (ICC) range
      0.92-0.99]. CONCLUSIONS: We obtained valid Spanish translations of the PFDI-20,
      PFIQ-7, QUID, and 3IQ. These results support their use as clinical and research
      assessment tools in Spanish-speaking populations.

PMID- 22976531
TI  - Laparoscopic sacrocolpopexy for recurrent pelvic organ prolapse after failed
      transvaginal polypropylene mesh surgery.
AB  - INTRODUCTION AND HYPOTHESIS: A prospective case series to assess the safety and
      efficacy of laparoscopic sacrocolpopexy for the surgical management of recurrent
      pelvic organ prolapse (POP) after transvaginal polypropylene mesh prolapse
      surgery. METHODS: Between January and December 2010, women with post-hysterectomy
      recurrent prolapse (>= stage 2 POP-Q) after transvaginal polypropylene mesh
      prolapse surgery were included. Perioperative morbidity and short-term
      complications were recorded and evaluated. Surgical outcomes were objectively
      assessed utilising the Pelvic Organ Prolapse Quantification system (POP-Q), the
      validated, condition-specific Australian Pelvic Floor Questionnaire (APFQ) and
      the Patient Global Impression of Improvement (PGI-I) at 12 months. RESULTS: All
      16 women in this study had undergone surgery with trocar-guided transvaginal
      polypropylene mesh kits. In 75% the recurrent prolapse affected the compartment
      of prior mesh surgery with the anterior (81%) and apical (75%) compartment
      prolapse predominating. At a mean follow-up of 12 months, all women had
      resolution of awareness of prolapse, had < stage 2 POP-Q on examination and high
      levels of satisfaction on PGI-I post surgery. There were no serious peri- or
      postoperative complications. CONCLUSIONS: This preliminary study suggests that
      laparoscopic sacrocolpopexy for recurrent prolapse after failed transvaginal mesh
      surgery is feasible and safe. Further widespread evaluation is required.

PMID- 22976530
TI  - Oxybutynin: past, present, and future.
AB  - Oxybutynin chloride is primarily indicated for the treatment of overactive
      bladder syndrome (OAB). It remains the most widely prescribed compound for OAB in
      the world. OAB is defined as the presence of urinary urgency, usually accompanied
      by daytime urinary frequency and nocturia, with or without urgency urinary
      incontinence, in the absence of infection or other identifiable etiology. This is
      a significant problem for men and women said to affect over 33 million adults in
      the USA, with the prevalence increasing with age. These symptoms can alter
      quality of life, with both physical and psychological impairment, as well as
      cause significant financial burden including the cost of sanitary supplies and
      decreased work productivity. Both pharmacological and non-pharmacological methods
      may be employed to aid in the treatment of OAB. The mainstay of treatment for OAB
      relies on pharmacological management, most specifically treatment with
      antimuscarinic medications. These medications are thought to prevent involuntary
      bladder contractions and/or urgency by inhibiting the muscarinic receptors within
      the urothelium and detrusor muscle. Currently, there are six different
      medications approved by the US Food and Drug Administration (FDA) for the
      treatment of OAB, with more than nine formulations including immediate- and
      extended-release tablets, transdermal patch and gel, vaginal ring, and
      suppository. This review will focus specifically on oxybutynin chloride, which
      has been used to treat OAB for four decades in numerous formulations.

PMID- 22976532
TI  - Repeat mid-urethral sling for recurrent female stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to assess the effectiveness
      of repeat mid-urethral sling after a failed primary sling for stress urinary
      incontinence. METHODS: A total of 112 women with recurrent stress incontinence
      after primary mid-urethral sling underwent a repeat procedure between 2000 and
      2011. All patients had a preoperative clinical and urodynamic evaluation.
      Outcomes were divided into three groups: cured (no more leaks), improved
      (decrease of leaks), or failed. RESULTS: All patients had urethral hypermobility
      and 12.9 % had intrinsic sphincter deficiency [maximum urethral closure pressure
      (MUCP) <= 20 cmH2O]. Median MUCP was 41 cmH20. Overactive bladder was found in
      5.7 % of women. The second sling placed was one of the following: retropubic
      Tension-free Vaginal Tape (49 %), transobturator tape (48 %), or mini-sling (3
      %). No intraoperative morbidity was reported. After the second sling was placed,
      68 (60.7 %) patients were subjectively cured and 18 (16.1 %) improved (76.8 %
      success overall) with a mean follow-up of 21 months. Success rates were 72.2 and
      81.8 % for transobturator and retropubic slings, respectively, with no
      significant difference. Multivariable analysis showed higher odds of cure and
      improvement with the retropubic approach after adjusting for MUCP. Late
      complication rates were comparable to those observed after a first sling.
      Urodynamic parameters were not associated with postoperative success.
      CONCLUSIONS: Repeat mid-urethral sling for recurrent female stress urinary
      incontinence is nearly 77 % successful in a group of patients with persistent
      urethral hypermobility. A retropubic approach might be preferred for patients
      with low urethral closure pressures.

PMID- 22976533
TI  - Electrical stimulation of the abdomen preserves motor performance in the inactive
      elderly: a randomized controlled trial.
AB  - Abdominal muscle strength declines easily with the process of aging and/or
      disuse, and it is difficult to strengthen weak abdominal muscles in the inactive
      elderly.  In the present study, we applied surface electrical stimulation (ES) to
      the abdomen of inactive elderly people to investigate its chronic effects. 
      Twenty inactive elderly people (65-89 years) who spent most of the day in their
      bedroom participated in the study.  The subjects were assigned to ES and non-ES
      groups in a random order.  In addition to conventional physical therapy and
      occupational therapy, ES was applied to both sides of the flank of 10 subjects
      (ES group) for 8 weeks.  For evaluation of the abdominal muscles, the cross
      sectional area (CSA) was measured with computed tomography and the electrical
      muscle activity (iEMG) was measured by electromyography.  Functional examinations
      were performed at 2, 4, and 8 weeks after the beginning of the study with the
      following parameters: grip strength; maximum walking speed (WS); movement time
      for sitting up (MSU); number of trunk flexions (NTF); flexibility of the trunk;
      sit-to-stand time (STS); and Barthel index (BI) score.  In the ES group, the NTF
      and MSU were significantly improved at 4 weeks and thereafter.  Furthermore, the
      STS and WS were also improved significantly after 8 weeks (p < 0.05).  The CSA
      and iEMG both increased significantly (p < 0.05).  However, the flexibility of
      the trunk and BI score did not change.  In conclusion, ES to the abdomen has the
      potential to improve motor function in the inactive elderly.

PMID- 22976534
TI  - Healing processes of the glenoid labral lesion in a rabbit model of shoulder
      dislocation.
AB  - Traumatic dislocation most commonly occurs at the shoulder joint.  After an
      initial dislocation of the shoulder, the labrum is usually detached from the
      glenoid (Bankart lesion).  If this lesion fails to heal, surgical repair is
      necessary.  The purpose of this study was to determine the histological and
      biomechanical healing process of a simulated Bankart lesion created in rabbits. 
      A labral injury was surgically created in 40 Japanese White rabbits.  The labrum
      was sharply dissected from the glenoid rim simulating a Bankart lesion, and was
      repositioned without sutures.  The joint capsule, the supraspinatus and
      infraspinatus tendons, and the deltoid were anatomically repaired with sutures. 
      Eight rabbits each were sacrificed at 1, 2, 3, 4, and 5 weeks after the surgery
      for histological and biomechanical examinations (4 animals each).  The histology
      and biomechanical properties of the normal capsulolabral structure was examined
      in 8 control rabbits.  Inflammatory cell infiltration into the gap between the
      glenoid and the labrum was noted from 1 week.  The gap was covered with fibrous
      connective tissue accompanied by the collagen fibers by 3 weeks.  The healing
      process was completed histologically by 3 weeks.  Biomechanically, the tensile
      load, which decreased significantly at 1 week, gradually increased and returned
      to the level of intact shoulder at 4 weeks.  At least four weeks are necessary
      for the healing of the labral injury in rabbits.  Considering the difference
      between humans and rabbits, it seems reasonable to let the patients go back to
      sports 2 to 3 months after dislocation or surgical repair.

PMID- 22976535
TI  - T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells
      following binding of bispecific tetravalent antibody CD19 * CD3 or CD19 * CD16.
AB  - Bispecific tetravalent antibodies (TandAb) directed against the B cell surface
      marker CD19 and activating receptors on T or NK cells (CD19 * CD3 or CD19 * CD16)
      have shown promising effects in vitro and in preclinical studies. Here, we
      examine the cytotoxic efficacy of T and NK cells from patients with B cell Non
      Hodgkin's Lymphoma (NHL) against B-lymphoma cells following the binding of the
      matching TandAb. The addition of CD19 * CD16 TandAb led to a threefold increase
      in NK cell activation in the presence of B-lymphoma cells. Similarly, T cells
      displayed a sevenfold increase in cytotoxic activity after the addition of CD19 *
      CD3 TandAb. Comparison of T and NK cell effector function of patients and healthy
      controls showed comparable levels of cytotoxic activity in response to lymphoma
      cells and no reduction in functional activity due to age, disease stage or the
      type and amount of previous therapy. Thus, T and NK cells of patients with B cell
      NHL are fully capable of being activated by therapeutic crosslinking antibodies.
      These results provide a rationale for the use of TandAbs for patients with B cell
      NHL, particularly in cases where remission with minimal residual disease could be
      achieved by cytotoxic chemotherapy.

PMID- 22976537
TI  - Vitamin D, immune tolerance, and prevention of type 1 diabetes.
AB  - Vitamin D is a secosteroid hormone that resembles other nuclear steroid hormones
      such as thyroid, gluco-, and mineralocorticoids, as well as gonadal effector
      systems. Primarily understood as a master regulator of bone and calcium/phosphate
      physiology, it is now increasingly recognized as orchestrating numerous aspects
      of cell growth and differentiation in many tissues, including those of innate and
      acquired immunity. This review addresses recently discovered aspects that
      highlight vitamin D's potential for immune intervention and how the vitamin D
      pathway is utilized for anti-infective and antineoplastic immunity. This provides
      the rationale for novel therapeutic strategies in the context both of prevention
      and of therapy of immune dysregulation in type 1 diabetes.

PMID- 22976538
TI  - Strategies to reduce diabetes disparities: an update.
AB  - Racial and ethnic minorities in the US have a higher prevalence, as well as
      suffer from more complications, lower quality care, and poorer outcomes for
      diabetes than their counterparts. Given the US health care system is in the midst
      of drastic transformation, with the passage of health care reform, and efforts in
      payment reform, and value-based purchasing, there is now support to provide more
      intensive, team-based care for those conditions that are complex, costly, and
      highly prevalent. Addressing and improving diabetes disparities, given they are
      prevalent and costly, will be an important area of focus in the years to come.
      The latest research demonstrates that community-based efforts, multifactorial
      approaches, and the deployment of health information technology can be successful
      in addressing diabetes disparities, and require support, attention, resources,
      and continued evaluation. Ultimately, these efforts should improve the quality of
      care for all persons with diabetes, especially those who are most vulnerable.

PMID- 22976539
TI  - Microsurgical reconstruction of the smile--contemporary trends.
AB  - The treatment of facial palsy is a complex and challenging area of plastic
      surgery. Microsurgical innovation has introduced the modern age of dynamic
      reconstruction for facial palsy. This review will focus on microsurgical
      reconstruction for smile restoration in patients with long-standing facial palsy.
      The most common donor muscles and nerves will be presented. The advantages and
      disadvantages of single-stage versus multi-stage reconstruction will be
      discussed. Contemporary trends will be highlighted and the authors' preferred
      practice outlined.

PMID- 22976540
TI  - Synthesis of push-pull chromophores by the sequential [2 + 2] cycloaddition of 1
      azulenylbutadiynes with tetracyanoethylene and tetrathiafulvalene.
AB  - Azulene-substituted butadiynes have been prepared by Cu-mediated cross- and homo
      coupling reactions. The azulene-substituted butadiynes reacted with
      tetracyanoethylene in a formal [2 + 2] cycloaddition reaction to afford the
      corresponding 1,1,4,4-tetracyanobutadiene chromophores, in excellent yields.
      Further [2 + 2] cycloaddition with TTF and TCNE gave novel donor-acceptor
      chromophores and novel azulene-substituted 6,6-dicyanofulvene derivatives.

PMID- 22976541
TI  - Recurrent and novel SS18-SSX fusion transcripts in synovial sarcoma: description
      of three new cases.
AB  - Synovial sarcoma (SS) is an aggressive type of tumor, comprising approximately 10
      % of soft tissue sarcomas. Over 90 % of SS cases are characterized by the
      t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of
      oncogenic SS18-SSX1 or SS18-SSX2 fusions. In a typical SS18-SSX fusion
      transcript, exon 10 of SS18 is fused to exon 6 of SSX1/2. However, several
      variant fusion transcripts have been already described. In the present study, we
      examined the fusion transcript type in a series of 40 primary untreated SS tumor
      specimens using reverse transcription polymerase chain reaction and fluorescence
      in situ hybridization assay. We detected SS18-SSX1 transcript in 22 (55 %)
      patients and SS18-SSX2 transcript in 17 (42.5 %) patients, while in one patient,
      none of SS18-SSX1/2 fusion transcripts were identified. Among the cases under
      study, two tumors carried novel SS18-SSX1 and SS18-SSX2 variant translocations
      that were allegedly created by an alternative splicing, and in additional case,
      an unusual translocation variant previously described by other group was found.
      Our data suggest that alternative splicing may play an important role in novel
      fusion transcript formation, and additionally we show that it may be a recurrent
      event in SS. Furthermore, we describe the first case of a complex rearrangement
      possibly linking SS to REPS2 gene.

PMID- 22976542
TI  - Tau expression correlated with breast cancer sensitivity to taxanes-based
      neoadjuvant chemotherapy.
AB  - The purpose of this study was to investigate the correlation between tau
      expression in primary breast cancer and sensitivity to taxanes during neoadjuvant
      chemotherapy in patients with breast cancer. We used immunohistochemistry to
      examine tau expression in breast cancer biopsies from 113 primary breast cancer
      patients and evaluated the correlation between tau expression and taxane
      sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau
      expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved
      pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR,
      five (12.5 %) were positive for tau expression. In univariate analysis, estrogen
      receptor (ER), progesterone receptor, human epidermal growth factor receptor 2
      (HER2), and tau were found to be significantly predictive of a pCR (P = 0.001,
      0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant
      for pCR on multivariate analysis (P = 0.025, 0.005, and 0.043, respectively). Tau
      expression was positively related to ER (P = 0.007) and progestin receptor (P =
      0.008). In conclusion, tau protein expression correlated with breast cancer
      sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau
      expression were more likely to achieve pCR.

PMID- 22976543
TI  - The expression of chemokines CCL19, CCL21 and their receptor CCR7 in oral
      squamous cell carcinoma and its relevance to cervical lymph node metastasis.
AB  - The purpose of this study is to determine the expression of CCL19, CCL21, and
      CCR7 in samples of oral squamous cell carcinoma (OSCC) and their relationship
      with clinical and microscopic parameters. A comparative analysis was made of the
      mRNA expression of these chemokines and receptor in OSCC and normal oral mucosa.
      The immunoexpression of CCR7, CCL19, and CCL21 was also verified in OSCC and
      lymph nodes. Statistical significance was accepted at P < 0.05. Similar levels of
      CCR7, CCL19, and CCL21 mRNA in OSCC and normal oral mucosa were seen. A low
      expression of CCL19 and CCL21 in the intra- and peritumoral regions was observed.
      Scarce CCL19(+) and CCL21(+) cells were also noted in metastatic and non
      metastatic lymph nodes. No association was found between the expression of these
      chemokines and clinical and microscopic parameters. Our findings would suggest
      that CCL19 and CCL21 may not be associated with cervical lymph node metastasis or
      other clinical and microscopic factors in OSCC.

PMID- 22976544
TI  - Formation and optogenetic control of engineered 3D skeletal muscle bioactuators.
AB  - Densely arrayed skeletal myotubes are activated individually and as a group using
      precise optical stimulation with high spatiotemporal resolution. Skeletal muscle
      myoblasts are genetically encoded to express a light-activated cation channel,
      Channelrhodopsin-2, which allows for spatiotemporal coordination of a multitude
      of skeletal myotubes that contract in response to pulsed blue light. Furthermore,
      ensembles of mature, functional 3D muscle microtissues have been formed from the
      optogenetically encoded myoblasts using a high-throughput device. The device,
      called "skeletal muscle on a chip", not only provides the myoblasts with
      controlled stress and constraints necessary for muscle alignment, fusion and
      maturation, but also facilitates the measurement of forces and characterization
      of the muscle tissue. We measured the specific static and dynamic stresses
      generated by the microtissues and characterized the morphology and alignment of
      the myotubes within the constructs. The device allows testing of the effect of a
      wide range of parameters (cell source, matrix composition, microtissue geometry,
      auxotonic load, growth factors and exercise) on the maturation, structure and
      function of the engineered muscle tissues in a combinatorial manner. Our studies
      integrate tools from optogenetics and microelectromechanical systems (MEMS)
      technology with skeletal muscle tissue engineering to open up opportunities to
      generate soft robots actuated by a multitude of spatiotemporally coordinated 3D
      skeletal muscle microtissues.

PMID- 22976545
TI  - tRNA processing by protein-only versus RNA-based RNase P: kinetic analysis
      reveals mechanistic differences.
AB  - In Arabidopsis thaliana, RNase P function, that is, endonucleolytic tRNA 5'-end
      maturation, is carried out by three homologous polypeptides ("proteinaceous RNase
      P" (PRORP) 1, 2 and 3). Here we present the first kinetic analysis of these
      enzymes. For PRORP1, a specificity constant (k(react)/K(m(sto))) of 3*10(6) M(-1)
      min(-1) was determined under single-turnover conditions. We demonstrate a
      fundamentally different sensitivity of PRORP enzymes to an Rp-phosphorothioate
      modification at the canonical cleavage site in a 5'-precursor tRNA substrate;
      whereas processing by bacterial RNase P is inhibited by three orders of magnitude
      in the presence of this sulfur substitution and Mg(2+) as the metal-ion cofactor,
      the PRORP enzymes are affected by not more than a factor of five under the same
      conditions, without significantly increased miscleavage. These findings indicate
      that the catalytic mechanism utilized by proteinaceous RNase P is different from
      that of RNA-based bacterial RNase P, taking place without a direct metal-ion
      coordination to the (pro-)Rp substituent. As Rp-phosphorothioate and inosine
      modification at all 26 G residues of the tRNA body had only minor effects on
      processing by PRORP, we conclude that productive PRORP-substrate interaction is
      not critically dependent on any of the affected (pro-)Rp oxygens or guanosine 2
      amino groups.

PMID- 22976547
TI  - 7,7'-Diamino-2,2'-diindolylmethane: a building block for highly efficient and
      selective anion receptors-studies in solution and in the solid state.
AB  - The easy-to-make 7,7'-diamino-2,2'-diindolylmethane was used as a building block
      for the construction of anion receptors operating by hydrogen bonds. Its various
      bisamide and bisurea derivatives were designed and synthesised as acyclic as well
      as macrocyclic molecules, then their structural and anion binding properties were
      studied in solution and in the solid state. The bisamide receptors demonstrate
      high affinity towards oxoanions in highly polar and partially aqueous solutions
      (DMSO with up to 25 % H(2)O) with significant selectivity for dihydrogen
      phosphate. Remarkably, the bisurea-based molecules are able to bind anionic
      guests even in pure methanol and show selectivity toward tetrahedral oxoanions,
      that is, hydrogen sulphate and dihydrogen phosphate. X-ray analysis revealed that
      both classes of molecules adopt a similar conformation in the solid state: a bent
      sheet shape with a binding pocket equipped with hydrogen-bond donors (four for
      the amides and six for the bisureas), whose orientation is particularly tailored
      for oxoanions. The results of ROESY NMR experiments are in agreement with the
      findings for the solid state and confirmed that both bisamides and bisureas can
      easily adapt the conformation with convergent hydrogen-bond donors, which is
      highly suitable for anion binding.

PMID- 22976548
TI  - Genetic and environmental causes of individual differences in daily life positive
      affect and reward experience and its overlap with stress-sensitivity.
AB  - Momentary positive affect (PA) and reward experience may underlie subjective
      wellbeing, and index mental health resilience. This study examines their
      underlying sources of variation and the covariation with stress-sensitivity. The
      experience sampling method was used to collect multiple appraisals of mood and
      daily life events in 520 female twins. Structural equation model fitting was
      employed to determine sources of variation of PA, reward experience, and the
      association between reward experience and stress-sensitivity. PA was best
      explained by shared and non-shared environmental factors, and reward experience
      by non-shared environmental factors only, although the evidence was also
      suggestive of a small genetic contribution. Reward experience and stress
      sensitivity showed no association. PA was not heritable. Most-if not all-variance
      of reward experience was explained by environmental influences. Stress
      sensitivity, indexing depression vulnerability, and reward experience were non
      overlapping, suggesting that resilience traits are independent from stress
      sensitivity levels in a general population sample.

PMID- 22976549
TI  - The development of exploratory behaviour in the african striped mouse rhabdomys
      reflects a gene * environment compromise.
AB  - Behaviour results from the interaction of an individual's genotype with
      prevailing environmental conditions, resulting in local adaptation to specific
      habitats. We investigated the development of exploratory behaviour in two closely
      related species of African striped mice from the semi-arid Succulent Karoo
      (Rhabdomys pumilio) and moist grassland (R. dilectus chakae) localities.
      Irrespective of sex, R. pumilio displayed greater exploratory behaviour (open
      field) and greater use of the open arms of a modified plus maze, and thus were
      less anxious and bolder than R. d. chakae. When pups were cross-fostered between
      species, fostered individuals of both species showed an intermediate behavioural
      pattern between their foster and biological siblings: fostered R. pumilio
      explored more than their foster siblings but less than their biological siblings,
      whereas fostered R. d. chakae explored more than their biological siblings, but
      less than their foster siblings. Our study is one of the first to address how the
      underlying genotype and early postnatal experience interact to influence the
      expression of exploratory behaviour and personality. In particular, we showed
      that, in striped mice, the early postnatal environment shapes the anxiety
      responses and concomitant exploratory behaviour, but the genotype apparently
      modulates the phenotype and constrains the limit of behavioural flexibility.

PMID- 22976546
TI  - Mammalian sleep genetics.
AB  - Mammalian sleep is a complex phenomenon governed by the interplay of neural
      circuits and signaling systems. The impact of genetic manipulations on sleep-wake
      dynamics provides important insights into this complex behavior. Here we review
      the sleep-related phenotypes of over 50 transgenic animal models spanning a
      variety of signaling systems. This heterogeneous literature includes outcomes
      spanning motor activity patterns, sleep-wake stage architecture, responses to
      sleep deprivation, circadian rhythmicity, and other perturbations such as food
      restriction, temperature challenge, and infection exposure. Insights from these
      animal experiments hold potential to converge with the well-known sleep-wake
      neurocircuitry as well as the increasingly available human genetic information,
      especially in patient populations exhibiting sleep-wake pathology.

PMID- 22976550
TI  - Migration and hypertension in Dakar, Senegal.
AB  - This article examines social and environmental influences on the development of
      hypertension in a sample of 568 adults (290 men; 278 women) aged 20 years and
      older from Dakar, Senegal. We test the hypothesis that more recent immigrants to
      the city of Dakar will have lower blood pressure and lower rates of hypertension
      than those who have lived there longer. Cross-sectional sociodemographic,
      anthropometric and blood pressure data were collected during 2009. The overall
      prevalence of hypertension was 27.1% (95% CI: 25.2-29.0). Hypertension rates were
      not significantly associated with place of birth; however, length of residence in
      Dakar was a significant predictor, with those living in the city for less than 10
      years having reduced risks of developing hypertension (OR = 0.25; P = 0.003).
      Other important correlates of blood pressure and hypertension risk in this sample
      were age and body mass index. These findings suggest that length of exposure to
      the urban environment-and associated changes in lifestyle-are linked to
      hypertension. Public health officials should thus pay particular attention to
      this phenomenon, and future anthropological research should include measures of
      both environmental and biological characteristics to study hypertension in
      Senegal.

PMID- 22976551
TI  - Increased plasma osmolar gap is predictive of contrast-induced acute kidney
      injury.
AB  - Contrast-induced acute kidney injury (CIAKI) is a common complication after
      percutaneous coronary artery intervention (PCI).  It is urgent to find a novel,
      easily measurable and accurate predictor for the early detection of CIAKI. 
      Hyperosmolarity and large amounts of contrast media are risk factors for CIAKI. 
      However, there is no study on plasma osmolar gap as a predictor of CIAKI.  We
      enrolled 89 patients undergoing elective PCI and tested changes of serum sodium,
      osmolar gap, and renal function at 0, 6, 12 and 24 hours.  Plasma osmolar gap was
      calculated using the following formula: measured plasma osmolarity - [2(Na) +
      serum urea nitrogen/2.8 + glucose/18].  CIAKI was defined as follows: increase in
      serum creatinine of >= 50%, increase in serum creatinine of >= 0.3 mg/dL, or
      decrease in estimated glomerular filtration rate of >= 25% within 24 hours after
      PCI.  The incidence of CIAKI was 13.5% (12/89 patients).  The CIAKI group had
      higher plasma osmolar gaps 6 hours after PCI.  The adjusted hazard ratio of the
      plasma osmolar gap from hour 6 (1-mOsm/L increments) to the development of CIAKI
      was 1.12 (95% confidence interval [CI], 1.01-1.26; P = 0.041).  Sensitivity and
      specificity of 7 mOsm/L or higher plasma osmolar gap at hour 6 were 70.0% and
      76.6%, respectively (area under the ROC curve = 0.77 [95% CI, 0.65-0.89]). 
      Increased plasma osmolar gap may precede the development of CIAKI in patients
      undergoing PCI.  In conclusion, plasma osmolar gap may be a useful predictor for
      the development of CIAKI.

PMID- 22976552
TI  - Comparing routes of IgG administration for primary immunodeficiency disorders.

PMID- 22976553
TI  - Treatment of neurological autoimmune diseases with immunoglobulins: first
      insights from the prospective SIGNS registry.
AB  - PURPOSE: Several immunoglobulin (IG) preparations have been approved for the
      immunomodulatory treatment of the neurological autoimmune diseases (AID) Guillain
      Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP),
      and multifocal motor neuropathy (MMN). Although efficacy has been proven in
      randomised clinical trials, long-term outcome data on drug utilization,
      effectiveness, tolerability, health related quality of life, and economic
      variables are lacking. METHODS: In the prospective, observational internet-based
      SIGNS registry, patients of all age groups are eligible if they have received or
      are scheduled for IG therapy for neurological AID or primary or severe secondary
      immunodeficiency. RESULTS: Of the 306 patients currently included in the database
      (1 November 2011), 51 have neurological AID (27 males; mean age 56 +/- 15 years):
      21 CIDP, 7 MMN, 11 multiple sclerosis (MS), 6 myasthenia gravis, 2 myositis, 4
      others (no cases of GBS). Mean duration of disease since first symptoms was 7.8
      years, and disease duration since diagnosis was 5.9 years. Eight different IG
      preparations have been reported as current therapy. According to SF-36, patients'
      quality of life is substantially impaired. CONCLUSIONS: Present data indicate
      some off-label use of IG (e.g. in MS) in patients with neurological AID. Quality
      of life in these patients is substantially compromised. Increasing patient
      numbers and extended follow-up periods will provide data on treatment concepts
      and disease development in AID patients.

PMID- 22976554
TI  - Neuromyelitis optica: potential roles for intravenous immunoglobulin.
AB  - Neuromyelitis optica (NMO) is an idiopathic central nervous system inflammatory
      demyelinating disease that causes optic neuritis, transverse myelitis, and other
      CNS syndromes. It is distinct from multiple sclerosis and is associated with
      autoantibodies that target aquaporin-4 (AQP4), an astrocyte water channel.
      Evidence indicating antibody-mediated immune injury in NMO includes its
      association with other autoimmune diseases, lesional pathology that reveals
      prominent complement activation and immunoglobulin deposition, pathogenic
      potential of AQP4 autoantibodies based on in vitro studies, and reports of
      putative animal models of the disease. The rationale and potential role for
      intravenous immunoglobulin in NMO will be discussed in the context of both
      relapse treatment and relapse prevention.

PMID- 22976555
TI  - Census of cytosolic aminopeptidase activity reveals two novel cytosolic
      aminopeptidases.
AB  - Activation of CD8(+) cytotoxic T cells is crucial for the adaptive immune
      response against viral infections and the control of malignant transformed cells.
      Together with activation of costimulatory molecules like CD3 and CD28, CD8(+) T
      cells need activation of their unique T cell receptor via recognition of foreign
      peptide epitopes in combination with major histocompatibility complexes class I
      on the cell surface of professional antigen-presenting cells. Presentation of
      pathogen-associated proteins is the result of a complex proteolytic process. It
      starts with the breakdown of proteins by a cytosolic endopeptidase, the
      proteasome, and is continued by subsequent N-terminal trimming events in the
      cytosol and/or the endoplasmic reticulum. Analysis of the proteolytic
      aminopeptidase activity in the former cellular compartment showed that the
      cytosol harbors a multitude of aminopeptidases that have singular specificities,
      but on the other hand also show redundancy in the trimming of N-terminal
      residues. The observed pattern of the overall trimming in the cytosol is
      reflected by the activity of the four identified aminopeptidases, and the
      administration of protease inhibitors made it possible to assign specificity of
      cleaving of proteinogenic amino acids to one or more identified aminopeptidase.
      The only exception was the cleavage of aspartic acid, which is performed by one
      yet unidentified enzyme.

PMID- 22976556
TI  - Immune control in the absence of immunodominant epitopes: implications for
      immunotherapy of cytomegalovirus infection with antiviral CD8 T cells.
AB  - Adoptive transfer of virus-specific donor-derived CD8 T cells is a therapeutic
      option to prevent cytomegalovirus (CMV) disease in recipients of hematopoietic
      cell transplantation. Due to their high coding capacity, human as well as animal
      CMVs have the potential to encode numerous CD8 T cell epitopes. Although the CD8
      T cell response to CMVs is indeed broadly specific in that it involves epitopes
      derived from almost every open reading frame when tested for cohorts of immune
      CMV carriers representing the polymorphic MHC/HLA distribution in the population,
      the response in any one individual is directed against relatively few epitopes
      selected by the private combination of MHC/HLA alleles. Of this individually
      selected set of epitopes, few epitopes are 'immunodominant' in terms of magnitude
      of the response directed against them, while others are 'subdominant' according
      to this definition. In the assumption that 'immunodominance' indicates
      'relevance' in antiviral control, research interest was focused on the
      immunodominant epitopes (IDEs) and their potential use in immunotherapy and in
      vaccines. The murine model has provided 'proof of concept' for the efficacy of
      CD8 T cell therapy of CMV infection. By experimental modulation of the CD8 T cell
      'immunome' of murine CMV constructing an IDE deletion mutant, we have used this
      established cytoimmunotherapy model (a) for evaluating the actual contribution of
      IDEs to the control of infection and (b) for answering the question whether
      antigenicity-determining codon polymorphisms in IDE-encoding genes of CMV strains
      impact on the efficacy of CD8 T cell immunotherapy in case the donor and the
      recipient harbor different CMV strains.

PMID- 22976559
TI  - Targeting the bacterial-host interaction: leveling the playing field.

PMID- 22976557
TI  - Classification of sleep disorders.
AB  - The classification of sleep disorders is necessary to discriminate between
      disorders and to facilitate an understanding of symptoms, etiology, and
      pathophysiology that allows for appropriate treatment. The earliest
      classification systems, largely organized according to major symptoms (insomnia,
      excessive sleepiness, and abnormal events that occur during sleep), were unable
      to be based on pathophysiology because the cause of most sleep disorders was
      unknown. These 3 symptom-based categories are easily understood by physicians and
      are therefore useful for developing a differential diagnosis. The International
      Classification of Sleep Disorders, version 2, published in 2005 and currently
      undergoing revision, combines a symptomatic presentation (e.g., insomnia) with 1
      organized in part on pathophysiology (e.g., circadian rhythms) and in part on
      body systems (e.g., breathing disorders). This organization of sleep disorders is
      necessary because of the varied nature and because the pathophysiology for many
      of the disorders is still unknown. The International Classification of Sleep
      Disorders, version 2 provides relevant diagnostic and epidemiological information
      on sleep disorders to more easily differentiate between the disorders.

PMID- 22976558
TI  - Insomnia pharmacotherapy.
AB  - The benzodiazepine receptor agonists (BzRAs) a melatonin receptor agonist and a
      histamine antagonist have all been approved as hypnotics. Beyond their differing
      mechanisms of action, they have differences in pharmacokinetics, and among the
      BzRAs differences in receptor subtype affinity and formulations, which provides
      the physician with broad options for tailoring therapy to each patient's specific
      needs. Consistent with their specific pharmacokinetics and formulations, these
      Food and Drug Administration-approved hypnotics have been shown to improve sleep
      with no evidence of tolerance development in long-term use. In addition, emerging
      data indicate these drugs also improve aspects of daytime function. Their side
      effects are either associated with the direct sedating effects of the drugs,
      doses greater than clinical doses, or a combination with alcohol or other
      sedating drugs. Anxiolytic BzRAs, sedating antidepressants and antipsychotics
      have been used off-label as hypnotics. However, in the absence of information
      regarding their dose range for efficacy and safety, their use as hypnotics is ill
      advised.

PMID- 22976560
TI  - Hydrogen bonding in Alzheimer's amyloid-beta fibrils probed by 15N{17O} REAPDOR
      solid-state NMR spectroscopy.

PMID- 22976561
TI  - Venous thrombosis of free flap immediately after intravenous application of
      desmopressin.

PMID- 22976562
TI  - High strength, flexible and transparent nanofibrillated cellulose-nanoclay
      biohybrid films with tunable oxygen and water vapor permeability.
AB  - A novel, technically and economically benign procedure to combine vermiculite
      nanoplatelets with nanocellulose fibre dispersions into functional biohybrid
      films is presented. Nanocellulose fibres of 20 nm diameters and several
      micrometers in length are mixed with high aspect ratio exfoliated vermiculite
      nanoplatelets through high-pressure homogenization. The resulting hybrid films
      obtained after solvent evaporation are stiff (tensile modulus of 17.3 GPa),
      strong (strength up to 257 MPa), and transparent. Scanning electron microscopy
      (SEM) shows that the hybrid films consist of stratified nacre-like layers with a
      homogenous distribution of nanoplatelets within the nanocellulose matrix. The
      oxygen barrier properties of the biohybrid films outperform commercial packaging
      materials and pure nanocellulose films showing an oxygen permeability of 0.07
      cm(3)    MUm m(-2) d(-1) kPa(-1) at 50% relative humidity. The oxygen
      permeability of the hybrid films can be tuned by adjusting the composition of the
      films. Furthermore, the water vapor barrier properties of the biohybrid films
      were also significantly improved by the addition of nanoclay. The unique
      combination of excellent oxygen barrier behavior and optical transparency
      suggests the potential of these biohybrid materials as an alternative in flexible
      packaging of oxygen sensitive devices such as thin-film transistors or organic
      light-emitting diode displays, gas storage applications and as barrier
      coatings/laminations in large volume packaging applications.

PMID- 22976563
TI  - Droplet electroporation in microfluidics for efficient cell transformation with
      or without cell wall removal.
AB  - An efficient cell transformation method is presented that utilizes droplet
      electroporation on a microfluidic chip. Two types of green microalgae, a wall
      less mutant and a wild type of Chlamydomonas reinhardtii, are used as model
      cells. The PDMS-glass electroporation chip is simply composed of a flow-focusing
      microstructure for generating cell-encapsulating droplets and a serpentine
      channel for better mixing of the content in the droplet, and five pairs of
      parallel microelectrodes on the glass slide, without involving any expensive
      electrical equipment. The transformation efficiency via the microfluidic
      electroporation is shown to be more than three orders of magnitude higher for the
      wall-less mutant, and more than two orders of magnitude higher for the wild type,
      which has its cell wall intact, than bulk phase electroporation under identical
      conditions. Furthermore, the microfluidic transformation is remarkably efficient
      even at a low DNA/cell ratio, facilitating ways of controlling the transgenic
      copy number, which is important for the stability of the transgene expression.

PMID- 22976564
TI  - Fibre-reinforced composite crowns luted to implant abutments via electroformed
      primary copings: an in vitro retention study.
AB  - AIM: The aim of this study was to investigate the retention values and mode of
      failure of metal crowns and fibre-reinforced composite crowns. METHODS: Seventy
      five implants and the corresponding abutments were used. After the galvanic
      copings were fabricated, the specimens were distributed into three groups: in
      group A traditional metal crowns were realized, whereas in groups B and C fibre
      reinforced composite crowns were made. In group B the same resin based cement
      used in group A was employed for luting the fibre-reinforced composite crowns to
      the galvanic copings, while in group C a dedicated self-adhesive composite cement
      was used. All galvanic coping/crown assemblies were cemented onto abutments with
      Panavia 21 cement. Specimens were subjected to a pull-out test; median retentive
      values and standard deviations were calculated. RESULTS: All samples in the group
      A showed separation at the abutment-galvanic cap interface. All samples in the
      group B showed decementation at galvanic cap-crown interface. In 13 samples of
      the group C the decementation occurred at the abutment-galvanic cap interface and
      in 12 samples of this group the decementation occurred at the galvanic cap-crown
      interface. The mean retention value was 659.1 N+/-162.9 for group A, 304.7 N+/
      101.4 for B and 635.4 N+/-155.9 for C. Differences between groups A/B and B/C are
      statistically significant (t-student test, P<0.01), while is not statistically
      different between groups A/C. CONCLUSION: When a self-adhesive composite cement
      is used, fibre-reinforced composite single crowns and conventional metal crowns
      show similar retentive performance.

PMID- 22976565
TI  - Condylar morphology in growing patients related to vertical dimension.
AB  - AIM: Aim of the study was to evaluate the mandibular morphology, especially the
      condylar one, in growing patients, according to the different vertical patterns.
      The objective was to analyze which condylar dimensions significantly vary in low,
      normal and high angle divergency growing patients with the use of the
      orthopantomogram (OPG). METHODS: From a database of randomly selected 514
      patients, 96 subjects (48 males and 48 females) with skeletal Class I according
      to lateral cephalograms were selected and divided in three equal groups in
      relation to their vertical dimension (32 low FMA angle, 32 normal FMA angle and
      32 high FMA angle). Each patient was examined with three OPGs at three different
      stages of dentition. OPGs were taken at the time of initial observation (T0 =
      first transitional phase of mixed dentition), after an average time of 12+/-1
      months (T1=inter-transitional phase of mixed dentition) and after 36+/-3 months
      (T2=second transitional phase of mixed dentition). The radiological technician
      and the radiologic device were the same for each x-ray. On each OPG, condylar and
      mandibular ramus morphology of both sides was traced. Eleven linear and angular
      measurements were reported on each tracing. Data were analyzed by Wilcoxon's
      signed rank test and the Student's t-test. RESULTS: The study showed different
      condylar characteristics according to the vertical patterns. Differences were
      evident between males and females. CONCLUSION: The length of the mandibular ramus
      resulted longer in short-face patients respect to long-face subjects.

PMID- 22976566
TI  - Effect of subgingival application of topical ozonated olive oil in the treatment
      of chronic periodontitis: a randomized, controlled, double blind, clinical and
      microbiological study.
AB  - AIM: The aim of this paper was to evaluate the efficacy of ozonated olive oil as
      a monotherapy and an adjunct to scaling and root planing in the treatment of
      chronic periodontitis METHODS: A split mouth, double-blinded, randomized
      controlled clinical trial was conducted on 20 subjects diagnosed with chronic
      periodontitis. Quadrants of each subject were randomly assigned to four groups
      and treated accordingly: Group A, scaling and root planing (SRP): Group B,
      topical ozonated olive oil (OZO) as an adjunct to scaling and root planing: Group
      C, topical ozonated olive oil as a monotherapy and: Group D, topical
      chlorhexidine gel as a monotherapy. The quadrants were analyzed clinically by
      plaque index, gingival index, sulcus bleeding index, probing pocket depth, and
      clinical attachment level at baseline, 2, 4, 6 and 8 weeks of time intervals. The
      subjects were also analyzed for perceived pain, discomfort or tooth
      hypersensitivity (quadrant wise) on a Visual Analogue Scale (VAS). Additionally,
      subgingival plaque samples were collected from the two predetermined sites of
      each quadrant at baseline, 4 and 8 weeks for the analysis of total bacterial
      counts (TBCs) and the detection of frequency of eight putative
      periodontopathogens by polymerase chain reaction (PCR) method. RESULTS: The
      adjunctive use of the OZO with SRP resulted in a significant improvement
      (P<0.001) of clinical parameters as well as microbiological parameters over the
      time and in comparison to the control groups. The OZO as monotherapy also showed
      a significant improvement (P<0.001) in clinical parameters as well as
      microbiological parameters over the time without any documented side effects.
      However, there was a significant increase (P<0.05) in dentinal hypersensitivity
      following OZO as an adjunct to scaling and root planing therapy. CONCLUSION: The
      OZO, as an adjunctive therapy as well as a mono-therapy is efficient in improving
      periodontal conditions.

PMID- 22976567
TI  - Chlorhexidine (CHX) in dentistry: state of the art.
AB  - Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in
      the dental field. It has a long-lasting antibacterial activity with a broad
      spectrum of action and it has been shown to reduce plaque, gingival inflammation
      and bleeding. Its use is considered a powerful adjuvant to mechanical oral
      hygiene (brushing and flossing), especially in those cases in which it cannot be
      performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX
      is considered a safe compound, with minimal and transitory local and systemic
      side effects. Data support its periodic use as an adjuvant to normal brushing and
      flossing in subjects unable to maintain proper oral hygiene due to physical
      and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX
      is also a useful alternative to mechanical oral hygiene procedures in those cases
      in which they are contraindicated, e.g. after a surgical procedure, or as a
      preoperative rinse before procedures in which use of a dental dam is not
      possible. The aim of this article is to offer a complete review of literature
      regarding the characteristics, the applications and the problems associated with
      the use of chlorhexidine in the dental field.

PMID- 22976568
TI  - Aspiration in intra-ligamental anaesthesia of lower first molar teeth: a pilot
      study.
AB  - AIMS: This pilot prospective, randomised, crossover study of positive aspiration
      frequency in intra-ligamental anaesthesia (ILA) was conducted with the following
      aims: (1) to determine the frequency of positive aspiration of blood after the
      administration of ILA at lower first molars, and (2) to evaluate the depth of the
      pulpal anaesthesia of lower first molars after positive or negative aspiration of
      blood, using electro-testing. METHODS: Intra-ligamental anaesthesia with 4%
      articaine with epinephrine was administered to the lower first molars of 36
      dental student participants. Pulpal analgesia of these 36 molars (17 left and 19
      right) was obtained after 114 intra-ligamental insertions, with 3.2 insertions on
      average, with the help of a computer syringe. The depth of pulpal analgesia after
      each insertion administration was assessed with electro-testing. RESULTS: A total
      of 114 intra-ligamental needle insertions were administered, of which 44 led to
      pulpal analgesia. After up to five administrations of ILA, all 36 molars achieved
      pulpal analgesia. In 34 of 36 (94.4%) subjects, ILA was accompanied by a positive
      aspiration test (AT). In the other two cases, successful but slow onset pulpal
      analgesia was obtained after five intra-ligamental needle insertions but with
      negative ATs. CONCLUSIONS: For the first time, the aspiration of blood after the
      administration of ILA has been studied. The frequency of positive aspiration of
      blood and successful pulpal analgesia was 94%. There was a very strong
      association between positive aspiration of blood after ILA and good pulpal
      analgesia. When there was negative aspiration of blood after the administration
      of an ILA, in rare cases pulpal analgesia developed after a delay of 3-5 minutes.

PMID- 22976569
TI  - Oral manifestations in chronic renal failure patients attending two hospitals in
      North Karnataka, India.
AB  - AIM: To determine the nature, incidence, and severity of oral manifestations that
      occur in chronic renal failure (CRF) in patients attending two hospitals in North
      Karnataka, in comparison with healthy, disease-free controls. METHODS: The study
      was carried out with 200 individuals (100 CRF patients and 100 controls). The
      case group was randomly selected from a population of CRF patients whose
      glomerular filtration rate (GFR) values were between 15-30 mL/min; the control
      group was selected in the same age group with normal GFR and was apparently
      disease free. The patients were asked about dry mouth, taste and halitosis, and
      mucosal pain, and were examined for oral changes such as tongue coating, pallor,
      ulceration and enamel hypoplasia. The results obtained from the study were then
      compared with various other similar studies. RESULTS: The most common oral
      findings in the CRF patients were dry mouth (91%), pallor (87%), altered taste
      (42%), and halitosis (34%). CRF patients showed significantly more oral changes
      than those in the control group. These changes could be attributed to metabolic
      disturbances due to renal failure. CONCLUSION: In the patients studied, the
      impact of CRF on the oral cavity was evidenced by significant oral changes, which
      pointed to an inter-relationship between oral health and CRF. Further studies are
      required to relate the extent of such changes with disease progression.

PMID- 22976570
TI  - Oral complaints of denture-wearing elderly people living in two nursing homes in
      Istanbul, Turkey.
AB  - AIM: The aim of this study was to observe and determine oral complaints of people
      aged 55 years or older, living in two nursing homes in Istanbul, Turkey, and
      their satisfaction with their complete or partial dentures by means of a simple
      questionnaire. METHODS: Two old people's homes (one public and one private) in
      the district of Uskudar in Istanbul agreed to take part in this study. All
      residents who were available were invited to answer a piloted nine-point
      questionnaire with questions on age, gender, physical problems, eating, and
      communication, aesthetic denture wearing and psychological problems. The
      questions were asked in person by one investigator. The resulting data were
      entered into SPSS version 15. RESULTS: Out of a total of 210 residents, 130
      (61.9%) took part in the study, of whom 53% (n=71) of residents were living in
      the private nursing home and 60% (n=81) were female. One hundred and five (80%)
      were denture wearers. More than half of the residents (59%, n=79) were over 75
      years old. Problems were mostly seen in older ages, especially those over 75
      years old, over 60% of whom reported problems for all the variables listed in the
      questionnaire. Women were more aware of halitosis than men. CONCLUSIONS: The
      results of this study confirm those of previous studies and suggest that elderly
      people with dentures, and particularly complete dentures, frequently complain of
      a wide range of problems including: eating, social interaction and communication
      and these problems have a detrimental influence on their quality of life.

PMID- 22976571
TI  - Prevalence of traumatic dental injuries in children who attended two dental
      clinics in Targu Mures between 2003 and 2011.
AB  - AIMS: This retrospective study aimed to assess the prevalence of dental trauma in
      deciduous and permanent teeth among children and teenagers who attended two
      dental clinics in Targu Mures, Romania, between 2003 and 2011 and the correlation
      of their risk of dental trauma with factors, including gender, age, physical
      activities and extent of incisor overjet. METHODS: The study population consisted
      of patients aged between 1 and 18 years who attended the Clinic of Paediatric
      Dentistry and Orthodontics and the Clinic of Oral and Maxillofacial Surgery,
      Targu Mures, in the period between January 2003 and August 2011. Their records
      were reviewed and the following factors, relevant to dental trauma, were
      recorded: gender, age, type of dentition, injury aetiology, lesion type and
      location, number of teeth affected, occlusion, and radiography. For patients who
      attended the orthodontics clinic, the degree of overjet was also determined.
      RESULTS: The overall prevalence of dental trauma was 24.5%. The frequency of
      traumatic injuries to deciduous teeth was approximately equal for boys and girls,
      and the most for those between 1 and 2 years. In the permanent dentition, a
      dental trauma was more frequently found boys, and the most affected age group was
      between 11 and 12 years, for both boys and girls. The most common causes were
      falls, in deciduous teeth especially during learning to walk, and in permanent
      teeth particularly during cycling or other sporting mishaps. The most frequent
      type of trauma found in the deciduous dentition was lateral luxation and in the
      permanent teeth it was fracture with the involvement of enamel and dentine, but
      without the exposure of the dental pulp. A positive relationship was noted
      between the presence of overjet associated with lip incompetence and the
      frequency of dental trauma. CONCLUSIONS: The prevalence of dental trauma in
      children and adolescents who attended the Clinic of Paediatric Dentistry and
      Orthodontics and the Clinic of Oral and Maxillofacial Surgery, Targu Mures, was
      broadly similar to that found in other studies. More epidemiologic studies are
      needed to gain a more comprehensive overview of the prevalence of dental trauma
      in Romania.

PMID- 22976572
TI  - Oral considerations in the management of sickle cell disease: a case report.
AB  - The phenomenon of erythrocyte sickling observed in sickle cell anaemia is
      responsible for ischaemia and tissue infarction compromising several organs and
      systems including the mouth and face. This brief paper reports the case of a 17-
      year-old female with a complicated sickle cell anaemia, hypertension and
      paraplegia (after an ischaemic stroke at the age of six years). Oral examination
      revealed the absence of tooth 12, fractures of teeth 11, 21 and 22 (from trauma),
      active caries lesions in the enamel of teeth 36, 37 and 46, mucosal pallor, and a
      smooth tongue. Oral radiographs revealed bone rarefaction and trabecular bone
      coarsening. Dental surgeons and physicians should be aware of the general and
      oral abnormalities that can be present in individuals with sickle cell anaemia to
      allow for preventive measures and implementation of effective treatment options.

PMID- 22976573
TI  - Improving governance to improve oral health: addressing care delivery systems.
AB  - The evolving role of the state in the provision of health care has seen the
      adoption of new management philosophies to ensure that goals set for the system
      are reached. In particular, the term New Public Management (NPM) has tended to
      dominate reforms to help address perceived shortcomings in public sector
      services. NPM is based on the use of freemarket type arrangements as a mechanism
      to solve problems, the control of which provides new challenges. One particular
      challenge that has arisen from the combination of NPM with the large number of
      agencies involved in care provision is that of addressing the issues arising from
      the improved understanding of the determinants of health. This has led to the
      evolution of differing care arrangements across differing sectors at all levels.
      If resources are to be used as intended, the control of delivery systems to
      oversee their use must exist. The overarching term for such activity is a
      governance. This paper provides an overview of the issues that arise for
      addressing governance of oral health care and the subsequent challenges that face
      those responsible for ensuring compliance.

PMID- 22976574
TI  - Gingival recession associated with predisposing factors in young vietnamese: a
      pilot study.
AB  - AIMS: Several studies have shown a large diversity in the prevalence, extent and
      severity of gingival recession as well as controversial conclusions of its
      associated factors. Therefore, the aim of this pilot study was to evaluate
      gingival recession with predisposing factors in young Vietnamese. METHODS: A
      cross-sectional study using clinical examination was performed in 120 dental
      students. Oral hygiene status, tooth malposition and fraenal attachment were
      recorded. The width of keratinised gingiva was measured after mucosa staining
      with Lugol's iodine solution. Measurements of gingival recession were performed
      on labial tooth surfaces. Chisquare test, t-test and Pearsonas correlation were
      used for data analysis. RESULTS: The prevalence of gingival recession was 72.5%
      of the studied population. The extent of affected teeth was 11.1% of the examined
      teeth. The proportion of root-surface exposure was statistically higher (P<0.05)
      in the maxilla (12.5%) than in the mandible (9.6%). Premolars and right canines
      were the teeth most frequently and most seriously associated with gingival
      recession, respectively. There was a strong negative correlation between narrow
      width of keratinised gingiva and gingival recession (P<0.001). The recession was
      statistically associated with tooth malposition (P<0.001) but it was not related
      to high fraenal attachment and gender. CONCLUSIONS: A high prevalence of gingival
      recession was found in Vietnamese dental students. Gingival recession was
      associated with narrow width of keratinised gingiva, tooth malposition and
      maxillary teeth. Further studies performed in larger populations with more
      extended age groups are needed to confirm these findings.

PMID- 22976575
TI  - Management of gastric carcinoids (neuroendocrine neoplasms).
AB  - Gastric neuroendocrine neoplasms of the stomach can be divided into the usually
      well-differentiated, hypergastrinemia-dependent type I and II lesions and the
      more aggressively behaving gastrin-independent type III lesions. Mainly due to
      better diagnostics and awareness of this tumor, the observed incidence has
      increased more than tenfold over the last 30 years. Small (<15-20 mm) localized
      type I and II lesions that are slowly proliferating (Ki67<2%) can usually be
      managed conservatively with endoscopic surveillance. Reducing hypergastrinemia by
      surgical removal of an underlying gastrinoma is important in inhibiting growth
      and induce reduction of type II lesions, while the specific gastrin receptor
      antagonist YF476 or gastrin antibodies may become useful for both type I and II
      lesions. Infiltrating and metastasized tumors and type III lesions require a more
      aggressive approach with surgical resection and consideration of modalities such
      as somatostatin analogs, cytotoxics, and peptide receptor targeted treatment.

PMID- 22976576
TI  - Cue competition effects in the planarian.
AB  - The learning abilities of planarian worms (Dugesia tigrina) were assessed by
      using a number of Pavlovian conditioning paradigms. Experiment 1 showed that
      planaria were susceptible to basic conditioning in that they readily developed a
      conditioned response to a change in ambient luminance when it was consistently
      paired with an electric shock over a number of trials. In Experiment 2, the
      change in luminance was presented in a compound with a vibration stimulus during
      conditioning. Subsequent tests revealed poor conditioning of the elements
      compared with control groups in which the animals were conditioned in the
      presence of the elements alone, an instance of overshadowing. In Experiment 3,
      pre-training of one of the elements before compound conditioning resulted in
      blocking of learning about the other element. These results add to other studies
      that have reported cue competition effects in animal species belonging to
      different phyla (chordate, mollusk, arthropod), suggesting that learning in these
      phyla could be ruled by similar principles. The results are discussed adopting an
      evolutionary-comparative approach.

PMID- 22976578
TI  - Extraneural ependymoma: distant bone, lung, liver, and lymph node metastases
      following bevacizumab.
AB  - Extraneural metastases of ependymoma are rare, and have been reported in the
      lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone.
      We report a case of anaplastic ependymoma with distant metastases to the
      vertebral bones, lungs, liver, and lymph nodes following treatment with
      bevacizumab. Recent research has hypothesized that angiogenic tumors may develop
      means of resistance to antiangiogenic therapies, and some evidence suggests
      potential for antiangiogenic therapies to promote additional means for cancer
      spread. Nevertheless, antiangiogenic therapies continue to demonstrate potential
      as potent therapies for the treatment of many cancers, and should continue to be
      researched for future uses.

PMID- 22976577
TI  - Nutrient patterns and risk of fracture in older subjects: results from the Three
      City Study.
AB  - We investigated the association between nutrient patterns and risk of fractures
      in 1,482 older subjects. Patterns associated with higher intakes of Ca, P,
      vitamin B12, proteins and unsaturated fats, and moderate alcohol intake, provided
      by diets rich in dairies and charcuteries, were related to a lower risk of wrist
      and hip fractures. INTRODUCTION: The purpose of this study was to investigate the
      relationship between patterns of nutrient intake and the risk of fractures in
      older subjects. METHODS: Among 1,482 participants from the Bordeaux sample of the
      Three-City (3C) Study who completed a 24-h dietary recall and a food frequency
      questionnaire, we examined the association between patterns of nutrient intake
      derived from principal component analysis and 8-year incidence of self-reported
      fractures of the hip, the wrist, and the vertebrae. RESULTS: A "nutrient-dense"
      pattern rich in Ca and P, iron, vitamins B including B12, vitamins C and E,
      alcohol, proteins, and unsaturated fats, and characterized by a higher
      consumption of fruits and vegetables, meats and fish, cheese and milk,
      charcuteries, cereals, rice, pasta, and potatoes, was associated with a 19% (95%
      CI 2-34%, P=0.03) lower risk of wrist fractures. The same pattern was associated
      with a 14% (95% CI 2-25%) lower risk of fractures at any site. A "south-western
      French" pattern rich in Ca, P, vitamins D and B12, retinol, alcohol, proteins,
      and fats-including unsaturated fats; poor in vitamins C, E, and K, carotenes,
      folates, and fibers; and related to a higher consumption of cheese, milk, and
      charcuterie and a lower consumption of fruits and vegetables was related to a 33%
      lower risk of hip fractures (95% CI 3-39%, P=0.03). CONCLUSIONS: Higher intakes
      of Ca, P, vitamin B12, proteins, and unsaturated fats and moderate alcohol,
      provided by dietary patterns rich in cheese, milk, and charcuteries, were related
      to a lower risk of wrist and hip fractures in our cohort.

PMID- 22976580
TI  - Development of bacteria-based microrobot using biocompatible poly(ethylene
      glycol).
AB  - For the development of bacteria-based biomedical microrobot, we propose the
      fabrication method of biocompatible poly(ethylene glycol) (PEG) microbeads using
      a cross-junction microfluidic channel. PEG droplets were polymerized by
      ultraviolet (UV) irradiation to form PEG microbeads of 8.18 +/- 3.4 MUm diameter
      in a microfluidic channel. Generally, the bacteria did not attach to the surface
      of the PEG microbeads because of their hydrophilicity. We modified the selective
      surface of the PEG microbeads using poly-L-lysine (PLL), promoting attenuated
      Salmonella typhimurium adhesion using the submerging property of PEG microbeads
      on agarose gel: the bacteria could thus be attached to the PLL-coated surface
      region of the PEG microbeads. The selectively PLL-coated PEG microbeads group
      showed enhanced motility compared with the PLL-uncoated and completely PLL-coated
      PEG microbeads groups. The selectively PLL-coated PEG microbeads group showed
      12.33 and 7.40 times higher average velocities than the PLL-uncoated and
      completely PLL-coated PEG microbeads groups, respectively. This study verified
      the successful fabrication of bacteria-based microrobots using PEG microbeads,
      and the enhanced motility of the microrobots by selective bacteria patterning
      using agarose gel and PLL.

PMID- 22976579
TI  - Completion of guideline-recommended initial evaluation of atrial fibrillation.
AB  - BACKGROUND: Guidelines recommend evaluation of cardiac function, valvular and
      ischemic heart disease, and thyroid, kidney, and liver function on initial
      diagnosis of atrial fibrillation (AF). HYPOTHESIS: We hypothesized that initial
      workup of patients with newly identified AF would vary by age, sex, and burden of
      comorbid illness. METHODS: In a retrospective analysis of a large sample of
      commercially insured patients 18 to 64 years old (n = 40 245) and a nationally
      representative 5% cohort of Medicare beneficiaries 65 years or older (n = 204
      676), we measured claims for guideline-recommended services for initial
      evaluation of AF among patients with a new diagnosis between 2000 and 2008.
      RESULTS: From 30 days before through 90 days after AF diagnosis, basic
      evaluation, including physician visit, electrocardiogram, and echocardiography,
      was completed in up to 66.6% of patients. Completion rates for all guideline
      recommended evaluations were 17.4% in the commercially insured sample and 18.5%
      in the Medicare cohort in 2007. Evaluation rates increased over time. Blood tests
      assessing thyroid function were documented for approximately one-third of
      patients in each cohort. Increasing the observation period to 1 year before
      through 3 months after the AF diagnosis markedly increased completion rates, but
      rates of thyroid function testing remained low (50%-60%). There were minor
      differences in evaluation completeness by sex, race, and geographic region.
      CONCLUSIONS: Differences in guideline-recommended evaluation rates by demographic
      characteristics after a new diagnosis of AF were of minor clinical importance.
      Basic evaluation had satisfactory completion rates; however, rates of laboratory
      testing were low.

PMID- 22976581
TI  - Gait-specific metabolic costs and preferred speeds in ring-tailed lemurs (Lemur
      catta), with implications for the scaling of locomotor costs.
AB  - Metabolic costs of resting and locomotion have been used to gain novel insights
      into the behavioral ecology and evolution of a wide range of primates; however,
      most previous studies have not considered gait-specific effects. Here, metabolic
      costs of ring-tailed lemurs (Lemur catta) walking, cantering and galloping are
      used to test for gait-specific effects and a potential correspondence between
      costs and preferred speeds. Metabolic costs, including the net cost of locomotion
      (COL) and net cost of transport (COT), change as a curvilinear function of
      walking speed and (at least provisionally) as a linear function of cantering and
      galloping speeds. The baseline quantity used to calculate net costs had a
      significant effect on the magnitude of speed-specific estimates of COL and COT,
      especially for walking. This is because non-locomotor metabolism constitutes a
      substantial fraction (41-61%, on average) of gross metabolic rate at slow speeds.
      The slope-based estimate of the COT was 5.26 J kg(-1) m(-1) for all gaits and
      speeds, while the gait-specific estimates differed between walking (0.5 m s(-1) :
      6.69 J kg(-1) m(-1) ) and cantering/galloping (2.0 m s(-1) : 5.61 J kg(-1) m(-1)
      ). During laboratory-based overground locomotion, ring-tailed lemurs preferred to
      walk at ~0.5 m s(-1) and canter/gallop at ~2.0 m s(-1) , with the preferred
      walking speed corresponding well to the COT minima. Compared with birds and other
      mammals, ring-tailed lemurs are relatively economical in walking, cantering, and
      galloping. These results support the view that energetic optima are an important
      movement criterion for locomotion in ring-tailed lemurs, and other terrestrial
      animals.

PMID- 22976582
TI  - Uveal melanoma in England: trends over time and geographical variation.
AB  - AIMS: Uveal melanoma is the commonest primary intraocular malignancy in adults,
      and leads to death in approximately half of patients. The aim was to report on
      trends over time and geographical variation in rates of uveal melanoma in
      England. METHODS: Analysis of admissions for uveal melanoma, using linked English
      national hospital episode statistics, available from 1999 to 2010, and the Oxford
      record linkage study (ORLS), before that, from 1979 to 1998. RESULTS: The annual
      rate of people admitted in England with a new record of uveal melanoma remained
      stable at approximately 1.0 people per 100 000 population from 1999 to 2010.
      Annual ORLS incidence rates were also stable from 1979 to 1998. Proportions of
      new uveal malignancies in adults for 2006-10 were 88% (382 people/year) choroidal
      and 12% (52) ciliary body/iris. Incidence rates increased with increasing age and
      were higher in men than women. Geographical analysis showed variation across
      local authorities (LA) in incidence rates, from 0.1 to 1.9 people per 100 000
      population per year. Incidence rates at the LA level were inversely correlated
      with the proportion of black (r=-0.18) or Indian individuals (r=-0.13) in each
      LA, were weakly correlated with LA levels of social deprivation (r=0.08) and were
      not correlated with southerly latitude. CONCLUSIONS: The annual incidence of
      uveal melanoma in England has remained stable over the past decade. This
      contrasts with the rising incidence of cutaneous melanoma. Our data do not
      support the possibility that ultraviolet light exposure contributes to the
      pathogenesis of uveal melanoma.

PMID- 22976583
TI  - Central serous chorioretinopathy and risk of ischaemic stroke: a population-based
      cohort study.
AB  - BACKGROUND: Central serous chorioretinopathy (CSCR) is a common maculopathy that
      features choroidal circulatory disturbance. This population-based cohort study
      aimed to explore the relationship between CSCR and the future development of
      ischaemic stroke. METHODS: Data were obtained from Taiwan's national health
      insurance research database. From 2000 to 2007, 1814 patients with newly
      diagnosed CSCR were eligible for inclusion in the study cohort. Using stratified
      random sampling, 9648 enrollees matched with the study subjects in terms of sex,
      age, monthly income, geographical location and time of enrolment were selected as
      the control group. Stroke-free survival analysis was assessed using a Kaplan
      Meier method. Cox proportional hazard regressions were performed to calculate the
      HR of ischaemic stroke for the two groups after adjusting for possible
      confounding variables. RESULTS: Of the sampled patients, 45 (2.5%) from the CSCR
      cohort and 157 (1.6%) from the control group developed ischaemic stroke during a
      mean follow-up period of 3.9 +/- 2.2 years. CSCR patients had a significantly
      higher incidence of ischaemic stroke than those without a diagnosis of CSCR
      (p=0.003). After adjusting for age, sex and chronic comorbidities at baseline,
      CSCR patients were found to have a 1.56-fold (95% CI 1.11 to 2.18, p=0.010)
      greater risk of a subsequent ischaemic stroke than the matched controls.
      CONCLUSIONS: CSCR is an independent indicator for the increased risk of
      subsequent ischaemic stroke development.

PMID- 22976584
TI  - Ultrastructural and clinical evidence of subretinal debris accumulation in type 2
      macular telangiectasia.
AB  - AIMS: To describe subretinal debris found on ultrastructural examination in an
      eye with macular telangiectasia (MacTel) type 2 and on optical coherence
      tomography (OCT) in a subset of patients with MacTel type 2. METHODS: Blocks from
      the mid-periphery and temporal perifovea of an eye with clinically documented
      MacTel type 2 were examined with electron microscopy (EM). Cases came from the
      Sydney centre of the MacTel project and the practices of the authors. RESULTS: On
      EM examination, subretinal debris was found in the perifovea with accumulation of
      degenerate photoreceptor elements in the subretinal space. Despite the
      substantial subretinal debris, there was minimal retinal pigment epithelial (RPE)
      reaction. Focal defects were seen in the inner limiting membrane in the
      perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent
      yellow material at the fovea. OCT revealed smooth mounds between the RPE and the
      ellipsoid region. The material was hyperautofluorescent. CONCLUSIONS: This study
      suggests that subretinal accumulation of photoreceptor debris may be a feature of
      MacTel type 2. Ultrastructural and OCT evidence of disease beyond the
      vasculature, involving photoreceptors and Muller cells, is presented.

PMID- 22976585
TI  - Clinical outcomes of xeno-free allogeneic cultivated limbal epithelial
      transplantation for bilateral limbal stem cell deficiency.
AB  - PURPOSE: To report the clinical outcomes of allogeneic cell-based therapy for
      bilateral corneal blindness due to limbal stem cell deficiency (LSCD). METHODS:
      This retrospective study included 28 eyes of 21 patients, at least 8 years of
      age, with bilateral and total LSCD, treated between 2001 and 2010. A limbal
      biopsy was obtained from the eye of an adult living related donor. The limbal
      epithelial cells were cultivated in the laboratory using a xeno-free explant
      culture technique and transplanted onto the recipient eye after 10-14 days. All
      transplant recipients received topical and systemic immunosuppressants. RESULTS:
      At a mean follow-up of 4.8 +/- 2.8 years, 20 (71.4%) eyes maintained a completely
      epithelised, avascular and stable corneal surface, and among them 13 (46.4%) eyes
      subsequently underwent a penetrating keratoplasty (PK). The Kaplan-Meier survival
      rate of the PK allograft was 76.9 +/- 11.7% at 1 year with a median survival of
      3.3 years. Visual acuity improved to 20/60 or better in 19 (67.8%) eyes. No donor
      or recipient eyes developed serious ocular complications. CONCLUSIONS: Allogeneic
      cultivated limbal epithelial transplantation, followed by PK when needed, can
      successfully restore the ocular surface and improve vision in patients with
      corneal blindness due to bilateral LSCD.

PMID- 22976586
TI  - Non-aspiration technique to induce posterior vitreous detachment in minimum
      incision vitrectomy system.
AB  - Complete removal of the posterior hyaloid is an important procedure in vitrectomy
      for various vitreoretinal disorders. Although posterior vitreous detachment (PVD)
      can be usually induced by active aspiration of vitreous gel, it is difficult in
      cases where the posterior hyaloid attaches tightly to the retina, especially in
      minimum incision vitrectomy systems (MIVS) due to the smaller apertures of the
      instruments. We describe a novel technique of creating PVD without aspiration. In
      this method, a break in the vitreous cortex is initially made at the posterior
      precortical vitreous pocket using a diamond dusted membrane scraper. Once a break
      in the vitreous cortex is induced, the break is extended by continuing the same
      manipulation. Detachment of the posterior vitreous gradually progresses by the
      influx of irrigation fluid from the break into the space between the posterior
      vitreous and the retina. Subsequently, the scraper is inserted under the detached
      posterior hyaloid from the break in the cortical vitreous, and is lifted upward
      to complete the PVD. Complete PVD is confirmed by observation of the Weiss ring
      in front of the retina. Using this technique, PVD can be achieved in vitrectomies
      using MIVS, even when the posterior hyaloid attaches tightly to the retina.

PMID- 22976587
TI  - Scientific report: highlights of 25th ICAR, 16-19 April 2012, Sapporo, Japan.
AB  - Each year, the International Society for Antiviral Research (ISAR) organises a
      conference covering many differing aspects of antiviral research. The 25th
      International Conference on Antiviral Research (ICAR) was held in Japan. This
      special anniversary meeting was co-sponsored by the Japanese Association for
      Antiviral Therapy.This Workshop Report contains summaries of the four major
      lectures and each of the invited presentations in the Clinical symposium and in
      the three mini-symposia. Of the many interesting contributor presentations, there
      are brief summaries of a small selection of these. This report concludes with a
      few personal comments and observations.A brief summary of this report is included
      within the ISAR News published in this issue of AVCC.

PMID- 22976588
TI  - Opportunistic screening and health promotion for type 2 diabetes: an expanding
      public health role for the community pharmacist.
AB  - BACKGROUND: Early detection to identify people at risk of diabetes is an
      important approach to prevent or delay type 2 diabetes. This study aimed to
      implement the Diabetes Prevention Program in community pharmacy using a diabetes
      risk prediction tool. METHODS: The program was conducted in seven pharmacies in
      Bangkok, Thailand. Participants were the pharmacy's clients aged >= 35 years
      without the history of diabetes. A validated risk prediction tool was used to
      assess individuals' diabetes risk. Educational information was offered to all
      participants. Those with a high risk score (>= 9 out of 17) were offered a self
      check of fasting capillary blood glucose (CBG). A referral was made for those
      with CBG >= 126 mg/dl. RESULTS: During a 3-month service, 397 individuals
      participated in the program. Nearly half of the participants (49.4%) were at a
      high risk of diabetes (risk score: >= 9). Ninety five (48.5%) of these high risk
      individuals undertook fasting CBG. Elevated fasting CBG (>= 126 mg/dl) was found
      in 12 persons (12.7%). Overall, two patients with diabetes were identified during
      the provision of the program. CONCLUSIONS: The Diabetes Prevention Program in
      community pharmacies uncovered half of the clients who were at risk of diabetes
      and provided an opportunity for participants to learn more about the prevention
      of diabetes.

PMID- 22976589
TI  - Sex pheromone of the smaller clearwing moth Synanthedon tenuis (Butler).
AB  - The smaller clearwing moth, Synanthedon tenuis (Butler) (Lepidoptera: Sesiidae),
      is a major pest of persimmon in northeast Asia. A previous study reported
      attraction of S. tenuis males to Z3,Z13-18:OAc, but this compound had no effect
      on male catch in the persimmon orchards in Korea. In this study, we analyzed
      pheromone gland extracts of S. tenuis females and identified Z3,Z13-18:OH as the
      main component. In field trapping trial, Z3,Z13-18:OH alone was attractive to S.
      tenuis males and competitive with live virgin females. These results indicate
      that the pheromone of this species consists of a single component, Z3,Z13-18:OH.
      However, Z3,Z13-18:OAc, a previously reported attractant, was not detected in the
      gland extracts of females. Furthermore, the addition of Z3,Z13-18:OAc to the main
      pheromone component strongly inhibited attraction for males, suggesting that the
      diene acetate is not a pheromone component. This is the first report of an
      octadecadienol as female-produced sex pheromone from the genus Synanthedon.

PMID- 22976590
TI  - Defensive spiroketals from Asceles glaber (Phasmatodea): absolute configuration
      and effects on ants and mosquitoes.
AB  - Insects are the largest and most diverse group of organisms on earth, with over
      1,000,000 species identified to date. Stick insects ("walkingsticks" or
      "phasmids", Order Phasmatodea) are known for and name-derived from their
      camouflage that acts as a primary line of defense from predation. However, many
      species also possess a potent chemical defense spray. Recently we discovered that
      the spray of Asceles glaber contains spiroketals [a confirmed major component:
      (2S,6R)-(-)(E)-2-methyl-1,7-dioxaspiro[5.5]undecane, and a tentatively identified
      minor component: 2-ethyl-1,6-dioxaspiro[4.5]decane] and glucose. In this paper,
      we: 1) illustrate the identification of spiroketals and glucose in the defense
      spray of A. glaber by using Nuclear Magnetic Resonance (NMR), Gas
      Chromatography/Mass Spectrometry (GC/MS), and comparison with a synthetic
      reference sample; 2) provide the elucidation of the absolute configuration of the
      major spiroketal in that defense spray; and 3) demonstrate the effect of this
      compound and its enantiomer on both fire ants (Solenopsis invicta) and mosquitoes
      (Aedes aegypti).

PMID- 22976591
TI  - Scent chemicals of the brushtail possum, Trichosurus vulpecula.
AB  - The common brushtail possum (Trichosurus vulpecula) is the most widespread
      browsing marsupial in Australia, where it occupies woodland, agricultural, and
      urban environments. Following its introduction into New Zealand in the 19th
      century it has become a major feral pest, threatening native forests. The
      adaptability of the possum is thought to be due in part to its social
      organization, in which chemical communication is important. Possums have cloacal
      glands and exhibit related marking behavior. This study sought to characterize
      the chemicals involved in scent marking. Swabs were taken of the cloacal region
      of 15 possums (5 females, 10 males) from north-eastern Tasmania and analyzed by
      gas chromatography-mass spectrometry. There was a large number of compounds
      present, including 81 branched and unbranched, and saturated and unsaturated,
      fatty acids (C(4)-C(15)) and alcohols (C(6)-C(26)); 27 esters of 2,6- and 2,7
      dimethyloctanol; 29 esters of formic acid; 39 sulfur compounds including S(8) and
      a series of dialkyl disulfides, trisulfides, and tetrasulfides (C(4)-C(10)); and
      several alkylglycerol ethers. Many of these cloacal compounds are new to biology.
      There was considerable individual variability in the relative amounts of
      compounds found, and no evident sex differences, although the study was not
      designed to test this. This pattern suggests that these compounds may be acting
      collectively as a signature mixture of semiochemicals, carrying information on
      the individual, its kinship, and physiological and social status. This is the
      first detailed description of putative semiochemicals in any marsupial species.

PMID- 22976592
TI  - Second-look arthroscopic findings and clinical results after polyethylene
      terephthalate augmented anterior cruciate ligament reconstruction.
AB  - PURPOSE: Based on the revival of artificial ligaments containing polyethylene
      terephthalate, this study aimed to evaluate objective intra-articular findings
      within scheduled second-look arthroscopy, patient-reported clinical outcome and
      stability after isolated augmented ACL reconstruction with polyethylene
      terephthalate (Trevira(r)) augmented patella-bone-tendon-bone graft. METHODS: In
      a retrospective analysis of our institutional database, we found 126 patients
      with polyethylene terephthalate (Trevira(r)) augmented ACL reconstruction. All
      these patients underwent standardised second-look arthroscopic evaluation when
      removal of the augmentation became necessary. These second-look arthroscopic
      analyses focused on graft integration and remodelling in line with the
      polyethylene terephthalate augmentation. Arthroscopic re-examination comprised a
      graft evaluation including a structural and functional classification according
      to the Marburger Arthroscopy Score (MAS). Additional clinical evaluation was
      performed via the IKDC score and the scores of Tegner and Lysholm. Instrumental
      anterior laxity testing was carried out with a KT-1000TM arthrometer.
      Furthermore, a correlation analysis between the clinical parameters, the
      instrumental stability assessment and the corresponding arthroscopic graft
      condition was performed. RESULTS: The arthroscopic evaluation showed rupture of
      87 (69 %) of 126 augmentation devices. In 27 (31 %) of these 87 cases, synovial
      reactions were found particularly in the anterior compartment. An intact
      synthetic augmentation with signs of graft integration with intact synovial
      coating was only found in 30 %. Evaluation according to the MAS showed good to
      excellent structural and functional characteristics in 88 % of patients. Presence
      of a type III graft (MAS) was found in an additional 11 %. A rudimentary (type
      IV) graft was only detected once. Eighty-five percent of patients were graded A
      or B according to IKDC score. The Lysholm score was 92.4 +/- 4.8. Correlation
      analysis demonstrated a significant relationship between clinical outcome
      according to the IKDC score (p<0.05), instrumental stability performance
      according to the KT-1000TM assessment (p<0.05) and the corresponding arthroscopic
      graft evaluation according to the MAS. CONCLUSION: Graft integration and
      remodelling has complex and multi-factorial origins, particularly with artificial
      augmentation. Correlation analysis showed a significant relation between clinical
      condition, instrumental stability performance and arthroscopic graft
      constitution. The release of polyethylene terephthalate fibres caused
      inflammation of synovial tissue of the knee. Characteristic sub-clinical graft
      changes of structural, morphological and functional qualities of the inserted
      graft appear on second-look arthroscopy despite good clinical results.

PMID- 22976593
TI  - Anterior cruciate ligament reconstruction with the ligament augmentation and
      reconstruction system: a systematic review.
AB  - PURPOSE: The Ligament Augmentation and Reconstruction System (LARS) is a third
      generation of synthetic ligament, designed to overcome the issues of graft
      failure and synovitis which led previous generations of synthetic ligaments to
      fall out of favour. The theoretical benefits of LARS are appealing but this has
      not led to widespread uptake of the system in preference to autograft. The aim of
      this systematic review is to assess whether the evidence exists to support the
      use of LARS with respect to outcomes and complications. METHODS: A systematic
      search process was undertaken from January 1990 to June 2012 to identify primary
      evidence relating to the use of LARS in anterior cruciate ligament (ACL) single
      ligament reconstruction. RESULTS: Nine studies were found meeting the search
      criteria including a single randomised controlled trial, two comparative series
      and six further observational case series. Overall the methodological quality of
      the studies was poor with follow-up to a maximum of five years. Reported outcome
      scores were good for LARS and comparable to autograft techniques. Complication
      rates were low and comparable to those published for autograft techniques within
      the wider literature. Two reported incidences of synovitis were identified in
      case reports. CONCLUSIONS: The current literature supports the use of LARS in the
      short to medium term. However, high-quality studies with long-term follow-up are
      required to determine whether the use of LARS is preferable to autograft for ACL
      reconstruction over the longer term. Synovitis appears to be a rare complication
      closely related to imperfect graft positioning.

PMID- 22976594
TI  - Tuberculosis of the entheses.
AB  - PURPOSE: Tuberculosis of the osteoarticular system usually manifests as joint
      arthritis. There is no available English literature on the tubercular involvement
      of the enthesis (tendon-bone junction). METHODS: We performed a retrospective
      analysis on 14 patients with tuberculosis of the tendon-bone junction. Patients
      presenting with a sinus with or without presence of radiological evidence of bone
      destruction around the enthesis, and pain unresponsive to a trial of analgesics
      and physical therapy, were evaluated by closed or open biopsy for tuberculosis. A
      staging system is proposed for biopsy-proven tuberculosis of the enthesis.
      RESULTS: Between 2006 and 2010, we treated 14 patients with tuberculosis of the
      tendon-bone junction. Biopsy-proven cases of tuberculosis of the enthesis were
      administered anti-tubercular drugs for a period of one year. Sequestrectomy was
      performed in advanced lesions. The tendon-bone junction was rested until the
      features of its healing were clinically evident. The patients aged between 18 and
      52 years were followed up for an average of 1.7 years after cessation of anti
      tubercular drug therapy. They responded favourably, and none had recurrence of
      the disease. CONCLUSIONS: This study describes the tubercular involvement of the
      entheses, which heretofore has not been described in the literature. The rarity
      of its occurrence and lack of suspicion of an infectious aetiology in these
      locations frequently results in late diagnosis and incorrect initial treatment.
      This study also supports the "microtrauma theory" in the genesis of
      osteoarticular tuberculosis.

PMID- 22976595
TI  - Ligament regeneration using an absorbable stent-shaped poly-L-lactic acid
      scaffold in a rabbit model.
AB  - PURPOSE: Ligaments are frequently damaged in sports activities and trauma, and
      severe ligament injury can lead to joint instability and osteoarthritis. In this
      study, we aimed to regenerate the medial collateral ligament (MCL) using an
      absorbable stent-shaped poly-L-lactic acid (PLLA) scaffold in a rabbit model to
      examine the biocompatibility and mechanical properties. METHODS: Twenty-three
      Japanese white rabbits were used in this study. MCL defects were surgically
      created in the knee joints and then reconstructed using stent-shaped PLLA
      scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into
      the contralateral knees. Seven rabbits were sacrificed at three time points,
      conducted four, eight and 16 weeks after the operation. The regenerated tissues
      were histologically evaluated using fibre alignment scoring, morphology of
      fibroblast scoring and immunohistochemical analysis of types I and III collagen.
      The regenerated tissues were also biomechanically evaluated by measuring the
      ultimate failure load and stiffness. RESULTS: At four weeks post-operation,
      spindle-shaped cells were observed on the inside of the scaffolds. At eight
      weeks, maturation of the regenerated tissues and collagen fibre alignment
      parallel to the ligaments was observed. At 16 weeks, the fibre alignment had
      become denser. The fibre alignment and morphology of fibroblast scores
      significantly increased in a time-dependent manner. Expression of type I collagen
      was more strongly observed in the scaffold group at eight and 16 weeks post
      operation than at four weeks. Type III collagen was also observed at four, eight
      and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the
      ligament-bone junction at eight and 16 weeks. The ultimate failure load of the
      scaffold group was 46.7 +/- 20.7 N, 66.5 +/- 11.0 N and 74.3 +/- 11.5 N at four,
      eight and 16 weeks post-operation, respectively. There was no statistical
      difference between the normal MCL and the scaffold group at 16 weeks post
      operation. CONCLUSIONS: The stent-shaped PLLA scaffold allowed for MCL
      regeneration with type I collagen expression and fibrocartilage formation and
      resulted in sufficient mechanical function.

PMID- 22976596
TI  - Highly enantioselective and recyclable organocatalytic Michael addition of
      malonates to alpha,beta-unsaturated aldehydes in aqueous media.
AB  - A new type of pyrrolidine-based organocatalyst, which was developed earlier in
      our lab, has been found to be very effective for the Michael addition reaction in
      aqueous solvents involving a wide range of alpha,beta-unsaturated aldehydes and
      malonate derivatives. For the reactions studied, good to excellent yields (73%
      96%) and high to excellent enantioselectivities (up to 97%) were obtained using
      this catalyst. In addition, the catalyst could be recycled up to four times with
      gradual reductions in yields and enantioselectivity observed after the second
      cycle.

PMID- 22976597
TI  - Increased epicardial fat thickness is associated with cardiac functional changes
      in healthy women.
AB  - Epicardial fat tissue is a visceral fat depot with anatomical and functional
      contiguity to the myocardium and coronary arteries.  The objective of this study
      was to evaluate the association between epicardial fat thickness (EFT) and
      cardiac changes in healthy female subjects.  The study population consisted of
      ninety-six consecutive healthy female (mean age 31.1 +/- 6.7 years) who underwent
      transthoracic echocardiography.  EFT was measured by echocardiography.  Subjects
      were divided into two groups according to the EFT; EFT < 6 mm and EFT >= 6 mm. 
      The cardiac structural changes, increased left atrial volume indices (LAVI) (41.2
      +/- 9.9 vs. 52.6 +/- 12.5, p = 0.001) and left ventricular mass indices (LVMI)
      (129.6 +/- 32.1 vs. 155.6 +/- 31.6 p < 0.05), were observed in patients with
      increased EFT.  Myocardial tei index (MTI), which was used to evaluate both
      systolic and diastolic functions, was higher with increased EFT (0.44 +/- 0.07
      vs. 0.48 +/- 0.08, p = 0.02).  The correlation analysis revealed significant
      correlation between EFT and each of LAVI (r = 0.312, p = 0.002), LVMI (r = 0.301,
      p = 0.003), body mass index (BMI) (r = 0.8, p < 0.001), and MTI (r = 0.27, p =
      0.005).  Multivariate regression analysis demonstrated that EFT was associated
      with BMI (t = 5.28, p = 0.001), MTI (r = 2.39, p = 0.019), LVMI (r = 2.16, p =
      0.01), and LAVI (r = 3.21, p = 0.002).  In conclusion, EFT is an important
      predictor of cardiac alterations in women who are prone to obesity.

PMID- 22976598
TI  - Effects of heat treatment on Raman spectra of two-layer 12C/13C graphene.
AB  - The Raman spectra of two-layered graphene on a silicon substrate were studied in
      the temperature range from 298 to 1073 K in an inert atmosphere. Isotopic
      engineering was used to fabricate two-layer graphene specimens containing (13)C
      atoms in the top layer and (12)C atoms in the bottom layer, which allowed the
      behavior of each particular layer to be distinguished as a function of
      temperature. It is demonstrated that the top layer exhibits much lower Raman
      temperature coefficients than the bottom one for both the G and the G' modes. We
      suggest that the changes in the Raman spectra of graphene observed during thermal
      cycling are predominantly caused by a superposition of two effects, namely, the
      mechanical stress in graphene exerted by the substrate and the intrinsic changes
      in the graphene lattice caused by the temperature itself. The top graphene layer
      is proposed to be more relaxed than the bottom graphene layer and thus reflects
      almost exclusively the temperature variations as a freestanding graphene layer
      would.

PMID- 22976600
TI  - Vascularized periosteal graft from the first metatarsal bone: a new technique to
      prevent collapse of osteonecrosis of the talus in children. A case report.
AB  - Several microsurgical techniques have been described for the treatment of
      osteonecrosis of the talus (ONT). Recently reported in children, vascularized
      periosteal grafts showed promising revascularizing properties. We report a novel
      technique using a pedicled periosteal graft from the first metatarsal bone to
      treat steroid-induced early Ficat-Arlet stage III ONT in an 11-year-old boy. The
      patient presented initial favorable clinical and radiological results which were
      maintained at 34 months during the last follow-up. Through this original
      technique, and basing on the powerful osteogenic and vasculogenic propreties of
      periosteal flaps, we could effectively induce bone revascularization and prevent
      further collapse of the talar dome.

PMID- 22976599
TI  - Novel association of a PROC variant with ischemic stroke in a Chinese Han
      population.
AB  - Protein C (PC) is a well-characterized anticoagulant enzyme. However, the
      association between PC and ischemic stroke (IS) remains controversial. The aim of
      the present study was to investigate whether any genetic variant in the human
      protein C gene (PROC) was associated with susceptibility to IS in the Chinese Han
      population. All exons and the 5'- and 3'-untranslated regions of PROC were
      initially sequenced to identify informative variants. Potential abnormal variants
      were analyzed in a population of 788 IS patients and 1,200 healthy controls. The
      analysis was stratified by stroke etiology, and the results were replicated in
      262 IS patients and 288 healthy controls. Finally, functional studies were
      performed to evaluate the effects of the variant. A three-nucleotide
      duplication/deletion variant (c.574_576del) was identified and found to be
      significantly associated with IS (OR 2.56, 95 % CI 1.45-4.52, P = 0.001).
      Stratification by stroke etiology after adjustment for IS risk factors showed
      that this association persisted in the lacunar and cardioembolic subtypes (P <
      0.001 and P = 0.008, respectively) but not in the atherothrombotic and
      undetermined subtypes (P = 0.070 and P = 0.998, respectively). The functional
      studies showed a significant difference in the anticoagulant activity of PC in
      c.574_576del carriers and non-carriers (P < 0.001). Our results suggested that
      the novel PROC c.574_576del variant is a possible genetic determinant of an
      increased risk of IS and diminished anticoagulant activity of PC.

PMID- 22976601
TI  - Hand acupuncture and vascular injury.

PMID- 22976602
TI  - Water-soluble fullerene derivatives for drug discovery.
AB  - Fullerenes (represented by buckminsterfullerene, C(60)) are a new kind of organic
      compound with a cage-like structure. A great deal of attention has been focused
      on their unique properties. From the viewpoint of drug discovery, fullerenes
      could be novel lead compounds for drug discovery. However, fullerenes are poorly
      soluble in aqueous media. Incorporation of water-soluble groups into the
      fullerene core enables investigation of its biological activities. Certain
      fullerene derivatives show inhibitory activity against human immunodeficiency
      virus reverse transcriptase. Hepatitis C virus RNA polymerase is also inhibited
      by fullerene derivatives. Therefore, fullerene derivatives are candidate
      antiviral agents. In addition, fullerene derivatives exhibit antiproliferative
      activity by inducing apoptosis related to the generation of reactive oxygen
      species. Fullerene derivatives also have the potential to be anticancer drugs.

PMID- 22976603
TI  - The effect of maximum voided volume on response to desmopressin therapy in
      children with enuresis.
AB  - PURPOSE: This study was aimed to determine the effect of maximum voided volume
      (MVV) on the efficacy of desmopressin, which is commonly used to treat primary
      monosymptomatic nocturnal enuresis (PMNE) in children and adolescents. MATERIALS
      AND METHODS: Bladder capacity was measured with different methods in 52 patients
      with PMNE, and the effect of bladder capacity on desmopressin therapy was
      investigated. RESULTS: Patients with PMNE in whom MVV was 70% or less of
      estimated bladder capacity were found to be unresponsive to desmopressin therapy.
      CONCLUSION: The MVV can be measured before desmopressin therapy in patients with
      PMNE as a marker to predict treatment success. Our results suggest that
      desmopressin should not be used in patients with low MVV.

PMID- 22976604
TI  - Objective assessment of postoperative gastrointestinal motility in elective
      colonic resection using a radiopaque marker provides an evidence for the
      abandonment of preoperative mechanical bowel preparation.
AB  - BACKGROUND: It has been suggested that mechanical bowel preparation (MBP) has no
      benefit in terms of anastomotic healing, infection rate, or improvement in the
      postoperative course in patients undergoing elective colorectal surgery, and that
      it should be abandoned. However, the effect of MBP on postoperative
      gastrointestinal motility has been assessed subjectively. In this randomized
      trial, we objectively assessed the effect of MBP on postoperative
      gastrointestinal motility and mobility in elective colonic resection. METHOD: In
      total, 79 patients scheduled to undergo elective colonic resection for cancer
      were randomized to MBP or no-MBP groups prior to surgery. All patients ingested
      radiopaque markers before surgery to evaluate postoperative gastrointestinal
      motility, objectively evaluated by the transition of the markers at postoperative
      days (PODs) 1, 3, 5 and 7. The groups were then further subdivided into open and
      laparoscopic-assisted colectomy (LAC) groups and evaluated in terms of
      gastrointestinal motility and postoperative mobility. RESULTS: There was no
      significant difference between the no-MBP and MBP groups in terms of
      perioperative and postoperative course. In the LAC subgroup, there was no
      significant difference between the no-MBP and MBP groups in terms of marker
      transition. However, in the open subgroup, there was a significant difference
      between the groups in terms of the residual ratio of markers in the small
      intestine at POD 3 (no-MBP 35.3% vs. MBP 69.2%; p=0.041), excretion rate of
      markers at POD 5 (no-MBP 49.7% vs. MBP 8.8%; p=0.005), and residual ratio in the
      small intestine at POD 7 (no-MBP 3.1% vs. MBP 28.8%; p=0.028). Additionally, the
      excretion rate in the no-MBP group was significantly higher than in the MBP group
      at POD 7 (74.1% vs. 33.8%; p=0.007). CONCLUSIONS: Our data provide additional
      evidence to support the abandonment of MBP in elective open colonic surgery.

PMID- 22976605
TI  - Bone changes associated with soft-tissue tumors of the hand.
AB  - The purpose of this study was to clarify clinical and radiographic features of
      bone changes associated with soft-tissue tumors of the hand. We reviewed clinical
      records and radiographs of 115 patients who had undergone operations for soft
      tissue tumors or tumorous conditions of the hand. Bone changes were detected in
      the radiographs of 21 of the 115 patients. Giant cell tumor of tendon sheath was
      the most common histological type to be associated with bone changes. The most
      vulnerable part of the hand was the palmar side of the phalanx from the distal
      shaft to the head. Most of the bone changes were erosion with clear margins. The
      erosions tended to extend deeper into the bone with limited widening. "Steep
      deep" erosions were found in 5 patients; these erosions did not require
      reconstruction after surgical curettage, and tumors did not recur.

PMID- 22976606
TI  - Fatal tracheo-innominate artery fistula after tracheostomy in a patient with
      Pelizaeus-Merzbacher disease.
AB  - Tracheo-innominate artery fistula (TIF) is a serious, life-threatening
      complication following tracheostomy. We report a fatal TIF in a 15-year-old girl
      with Pelizaeus-Merzbacher disease. She received a tracheostomy for prolonged
      translaryngeal intubation due to acute respiratory failure without a trial of
      noninvasive ventilatory support before intubation. Severe hemorrhage from the TIF
      occurred 6 months after tracheostomy; immediate resuscitation failed. Antemortem
      fiberoptic bronchoscopy showed tracheal stenosis accompanied by granulation
      tissue, and postmortem examination revealed TIF with ulcerative granulation.
      Preventive intervention is required to avoid catastrophic TIF due to its high
      mortality rate. Moreover, to avoid prolonged translaryngeal intubation leading to
      tracheostomy, noninvasive ventilatory support before translaryngeal intubation,
      if applicable, is beneficial.

PMID- 22976607
TI  - Perinatal outcomes of failed vacuum extraction.
AB  - The aims of this study were to compare the perinatal outcomes of successful
      vacuum extraction (VE) or failed VE and to compare the perinatal outcomes of
      failed VE followed by forceps delivery (FD) or Cesarean section (CS) from 2000
      through 2007. Compared with cases of successful VE, cases of failed VE followed
      by CS had a significantly higher incidence of neonatal complications, whereas
      cases of failed VE followed by FD had a significantly higher incidence of
      maternal injury. Both CS and FD remain important yet distinct treatments for
      emergency cases of failed VE. Therefore, the decision to use a second instrument
      (FD) or to proceed to CS should be made in each case on the basis of these
      differences.

PMID- 22976608
TI  - Fore-lying of the umbilical cord after urination: a case report.
AB  - We present here a case of fore-lying of the umbilical cord. In this case,
      transvaginal sonography did not reveal the umbilical cord beyond the fetal head
      before maternal urination; however, 5 minute later, a fore-lying umbilical cord
      was revealed between the floating fetal head and the uterine cervix after
      urination. The present case indicates the importance of careful evaluation of
      preterm premature rupture of the membranes by means of transvaginal
      ultrasonography in predicting umbilical cord prolapse.

PMID- 22976609
TI  - A case of juvenile Sjogren's syndrome with interstitial nephritis.
AB  - Primary Sjogren's syndrome (SS) is a rare autoimmune disease, especially in
      children. Juvenile primary SS with interstitial nephritis is rare in Japan. We
      report on a 12-year-old girl in whom salivary gland swelling had recurred from
      the age of 5 years, SS was diagnosed at the age of 10 years, and interstitial
      nephritis developed at the age of 12 years. The patient presented with a chief
      complaint of swelling of both parotid glands. The patient had a history of
      recurrent parotitis from 5 years of age, with episodes recurring 5 to 6 times a
      year and resolving within 3 days each time. However, at the age of 11 years, the
      patient had continuous mild swelling of the parotid glands. Examination on
      admission showed bilateral nontender parotid gland swelling; mild swelling of the
      lower extremities, xerostomia, and xerophthalmia but no exanthem. Laboratory
      findings were as follows: serum protein, 10.1 g/dL; immunoglobulin (Ig) G, 3,828
      mg/dL; antinuclear antibodies, 1,280-fold; anti-Ro/SS-A antibody, 512-fold; anti
      Ro/SS-B antibody, 4-fold; creatinine, 0.45 mg/dL; blood beta2-microglobulin, 2.2
      mg/L (slightly elevated); and cystatin C, 0.86 mg/L. Urinalysis showed
      proteinuria and a beta2-microglobulin concentration of 11,265 mg/L. Thus, this
      patient had low molecular weight proteinuria. Schirmer's test showed decreased
      tear secretion (5 mm), and fluorescein staining showed marked bilateral
      superficial punctate keratitis. A lip biopsy showed infiltration by small round
      cells (mild to moderate), interstitial fibrosis, loss of salivary gland
      parenchyma, and atrophy, with no obvious epimyoepithelial islands, leading to a
      diagnosis of SS. Light microscopic examination of the renal biopsy specimens
      showed expansion of mononuclear cell infiltration in the renal interstitium,
      inflammatory cell infiltration of interstitial areas with edema and mild
      fibrosis, and tubulitis and mononuclear cell infiltration that included many
      lymphocytes and plasma cells. There were no pathological findings of
      glomerulonephritis. Small arteries showed no obvious abnormalities.
      Immunofluorescent staining showed slight, nonspecific deposition of IgM, but no
      deposition of IgG, complement 1q, 3, or 4. On the basis of the renal biopsy
      showing nonspecific chronic interstitial nephritis, renal tubular atrophy, and
      interstitial enlargement, tubulointerstitial nephritis associated with SS was
      diagnosed.

PMID- 22976610
TI  - Congenital dermoid cyst at the anterior fontanelle: neuroimaging before and after
      fontanelle closure.
AB  - We report on a 2-month-old boy with a dermoid cyst arising at the anterior
      fontanelle, with observation during both the open and closed stages of the
      fontanelle. The etiology of this benign, curable tumor is discussed.

PMID- 22976611
TI  - Ruptured feeder aneurysm associated with cerebellar arteriovenous malformation.
AB  - We report 2 cases of ruptured aneurysms of the posterior inferior cerebellar
      artery associated with an arteriovenous malformation (AVM). The aneurysm and AVM
      were simultaneously embolized with n-butyl cyanoacrylate. In one case both the
      aneurysm and the AVM were totally obliterated; in the other case the AVM was
      subsequently treated with radiosurgery. In both cases the aneurysms were
      successfully occluded. The effectiveness and limitations of this treatment are
      discussed.

PMID- 22976612
TI  - Subarachnoid hemorrhage of unknown etiology along the cortical convexity.
AB  - BACKGROUND: Only 8% to 22% of cases of subarachnoid hemorrhage (SAH) are of
      nonaneurysmal origin. Among these, perimesencephalic nonaneurysmal SAH is a
      distinct clinical and radiologic entity with normal angiographic findings and a
      good prognosis. In contrast, SAH of nonaneurysmal origin occurring along the
      cortical convexity is rare and poorly understood. We report 2 cases of
      subarachnoid hemorrhage along the cortical convexity and discuss their possible
      etiologies. METHODS: In a retrospective analysis of 234 patients with SAH, we
      identified 2 patients with a typical computed tomographic pattern of convexity
      SAH that was associated with no known etiology. RESULTS: In these 2 cases, the
      source of hemorrhage could not be identified with computed tomography, magnetic
      resonance imaging, or digital subtraction angiography, although neurovascular
      outcomes were good. The patients reported such incidents as coughing or exertion
      immediately before headache developed. These incidents may have caused increased
      intracranial pressure. CONCLUSION: We suggest the possible involvement of a brief
      increase in intracranial pressure, such as that accompanying coughing or
      exertion, in the occurrence of SAH along the cortical convexity.

PMID- 22976613
TI  - Lipoma of the finger with bone erosion.
AB  - Lipoma of the finger is rare, and there have been few case reports of lipoma
      causing bone erosion in the finger. We report on a patient with a long-standing
      lipoma that caused deep erosion of the distal phalanx of the index finger. A 38
      year-old man presented with a painful mass of the left index finger.
      Anteroposterior radiographic images showed a radiolucent area in slightly distal
      to the center of the distal phalanx. Magnetic resonance imaging revealed a large
      soft-tissue mass with high signal intensities and slight irregularity on both T1-
      and T2-weighted images which suggested lipoma. The patient underwent marginal
      excision of this tumor and curettage of the bone surface of the erosion. The pain
      resolved after surgery. The diagnosis of lipoma was confirmed with postoperative
      histological examination. Lipoma should be included in the differential diagnoses
      of a finger tumor, even if radiography shows bone erosion.

PMID- 22976614
TI  - Lessons learned from the Japan earthquake and tsunami, 2011.
AB  - On March 11, 2011, an earthquake occurred off the coast of Honshu, Japan. The
      quake was followed by a powerful tsunami that caused extensive damage to the east
      coast of the Tohoku and Kanto regions. This disaster destroyed the medical system
      in place and thus drastically reduced the ability of the healthcare system to
      handle the large number of casualties. During the initial response to this
      disaster, we participated in several types of outreach medical relief teams
      dispatched to the affected area from the day of the earthquake onwards. The ratio
      of persons injured to persons missing or dead for the 2011 Japan disaster (0.31:
      5,994 to 19,371) was much lower than for the Indian Ocean Tsunami of 2004 in
      Thailand (1.01; 8,457 to 8,393) and for the Great Hanshin-Awaji Earthquake of
      1995 in Japan (6.80; 43,792 to 6,437). The different ratios for the different
      types of disasters indicate that medical relief efforts in response to natural
      disasters should be tailored to the type of disaster to optimize the
      effectiveness of the response and prevent further deaths. From a medical
      viewpoint, unnecessary deaths must be prevented following natural disasters.
      Doing so requires appropriate information transmission and an understanding of
      the mission's overall and specific objectives: 1) rapid search and rescue; 2)
      early care in the field, evacuation centers, and primary clinics; 3) definitive
      evaluation at disaster base hospitals; and 4) proper evacuation to unaffected
      areas. We propose a descriptive device that can guide headquarters in dealing
      with the commonalities of a disaster.

PMID- 22976615
TI  - The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta
      analytic review.
AB  - This article describes a comprehensive meta-analysis that was conducted to
      estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD), as
      defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition (DSM-IV). A systematic literature review identified 86 studies of
      children and adolescents (N = 163,688 individuals) and 11 studies of adults (N =
      14,112 individuals) that met inclusion criteria for the meta-analysis, more than
      half of which were published after the only previous meta-analysis of the
      prevalence of ADHD was completed. Although prevalence estimates reported by
      individual studies varied widely, pooled results suggest that the prevalence of
      DSM-IV ADHD is similar, whether ADHD is defined by parent ratings, teacher
      ratings, or a best estimate diagnostic procedure in children and adolescents (5.9
      7.1 %), or by self-report measures in young adults (5.0 %). Analyses of
      diagnostic subtypes indicated that the predominantly inattentive type is the most
      common subtype in the population, but individuals with the combined type are more
      likely to be referred for clinical services. Additional research is needed to
      determine the etiology of the higher prevalence of ADHD in males than females and
      to clarify whether the prevalence of ADHD varies as a function of socioeconomic
      status or ethnicity. Finally, there were no significant prevalent differences
      between countries or regions of the world after controlling for differences in
      the diagnostic algorithms used to define ADHD. These results provide important
      support for the diagnostic validity of ADHD, and argue against the hypothesis
      that ADHD is a cultural construct that is restricted to the United States or any
      other specific culture.

PMID- 22976616
TI  - The regulation and role of neuronal gap junctions during neuronal injury.
AB  - In the mammalian CNS, excessive release of glutamate and overactivation of
      glutamate receptors are responsible for the secondary (delayed) neuronal death
      following neuronal injury, including ischemia, traumatic brain injury (TBI) and
      epilepsy. The coupling of neurons by gap junctions (electrical synapses)
      increases during neuronal injury. In a recent study with the use of in vivo and
      in vitro models of cortical ischemia in mice, we have demonstrated that the
      ischemic increase in neuronal gap junction coupling is regulated by glutamate via
      group II metabotropic glutamate receptors (mGluR). Specifically, we found that
      activation of group II mGluRs increases background levels of neuronal gap
      junction coupling and expression of connexin 36 (Cx36; neuronal gap junction
      protein), whereas inactivation of group II mGluRs prevents the ischemia-mediated
      increases in the coupling and Cx36 expression. Using the analysis of neuronal
      death, we also established that inactivation of group II mGluRs or genetic
      elimination of Cx36 both dramatically reduce ischemic neuronal death in vitro and
      in vivo. Similar results were obtained using in vitro models of TBI and epilepsy.
      Our study demonstrated that mechanisms for the injury-mediated increase in
      neuronal gap junction coupling are part of the mechanisms for glutamate-dependent
      neuronal death.

PMID- 22976618
TI  - Unusual presentation of sarcoidosis--involving testis, spinal cord and the brain.

PMID- 22976617
TI  - Primary Sjogrens syndrome is associated with impaired autonomic response to
      orthostasis and sympathetic failure.
AB  - BACKGROUND: Symptoms in keeping with autonomic dysfunction are commonly described
      by primary Sjogrens syndrome patients (pSS); whether objective abnormalities of
      autonomic function occur is unclear. This study set out to explore dynamic
      cardiovascular autonomic responses in pSS and their relationship with symptoms
      and quality of life. METHODS: Twenty-one people from the UK pSS registry, 21
      community controls and 21 patients with the autoimmune liver disease primary
      biliary cirrhosis (PBC) (matched case-wise for age and sex) attended for
      assessment of autonomic responses to orthostasis and Valsalva manoeuvre (VM). pSS
      patients also completed EULAR Sjogrens Syndrome patient-reported index (ESSPRI),
      EULAR Sjogren's syndrome disease activity index (ESSDAI), fatigue impact scale
      and EURO-QOL 5-dimension (EQ-5D). RESULTS: Compared with controls, pSS patients
      had significantly lower baseline systolic blood pressure (SBP) (114 +/- 13 vs.
      127 +/- 20; P = 0.02), which dropped to a significantly lower value (98 +/- 22
      vs. 119 +/- 24, P = 0.009). When area under the curve (AUC) was calculated for
      when the SBP was below baseline this was significantly greater in pSS compared to
      both control groups (pSS vs. control vs. PBC: 153 +/- 236 vs. 92 +/- 85 vs. 1.2
      +/- 0.3, P = 0.005). Peak phase IV SBP during the VM was significantly lower in
      pSS (P = 0.007) indicating early sympathetic failure. Increased heart rate
      associated with fatigue (P = 0.02; r(2) = 0.2) and EQ-5D. A shift in sympathetic
      vagal balance associated with overall symptom burden (ESSPRI) (P = 0.04, r(2) =
      0.3) and EULAR sicca score (P = 0.016; r(2) = 0.3), the latter also correlated
      with baroreceptor effectiveness (P = 0.03; r(2) = 0.2) and diastolic blood
      pressure variability (P = 0.003; r(2) = 0.4). CONCLUSION: pSS patients have
      impaired blood pressure response to standing. Dysautonomia correlates with PSS
      associated symptoms and quality of life.

PMID- 22976619
TI  - Intrathoracic gastric volvulus.

PMID- 22976620
TI  - Razor blades in the stomach.

PMID- 22976621
TI  - Possible failures in certain aspects of the health care system that will need
      attention.

PMID- 22976622
TI  - Changing epidemiology of nonsyndromic craniosynostosis and revisiting the risk
      factors.
AB  - Recent studies in Europe and the United States report increased incidence of
      metopic synostosis. Whether a similar trend had occurred in Australia remains
      unknown. This research aimed to determine changes in incidence and subtypes of
      craniosynostosis in Victoria and to identify perinatal risk factors. A
      retrospective audit of patients (n = 522) presenting to the Royal Children's
      Hospital in Melbourne with nonsyndromic craniosynostosis from 1982 to 2008 was
      undertaken. Perinatal data were sourced from the Victorian Perinatal Data
      Collection. The changes in incidence of craniosynostosis subtypes were calculated
      based on Poisson regression, and risk factors for craniosynostosis and subtypes
      were analyzed by univariate logistic regression analysis. The prevalence of
      nonsyndromic craniosynostosis was 3.1 in 10,000 live births in Victoria. On
      average, the incidence of nonsyndromic craniosynostosis increased by 2.5% per
      year among Victorian live births. Over 25 years, metopic synostosis incidence
      significantly increased by 7.1% per year in the population of Victoria, outpacing
      other subtypes. The risk factors for metopic synostosis include being male,
      multiple births (ie, twins), preterm gestation, low birth weight, high maternal
      age, and emergency cesarean birth. This study revealed a true increase in
      incidence of metopic synostosis in Victoria, which could be a result of increased
      frequency of multiple births, preterm gestation, low birth weight, and high
      maternal age in the Victorian population from 1982 to 2008. The incidence of
      other nonsyndromic craniosynostoses, which include sagittal, unicoronal, and
      multisutural craniosynostoses, however, has remained unchanged.

PMID- 22976623
TI  - Association between PAX9 single-nucleotide polymorphisms and nonsyndromic cleft
      lip with or without cleft palate.
AB  - The purpose of this study was to investigate the contribution of PAX9 gene to the
      risk of nonsyndromic cleft lip with or without cleft palate (NS-CL/P). The
      samples consisted of 142 Korean NS-CL/P families (90 males and 52 females; 9
      cleft lip, 26 cleft lip and alveolus, and 107 cleft lip and palate; 76 trios and
      66 dyads). A total of 10 single-nucleotide polymorphisms (SNPs) were tested for
      association with Korean CL/P case-parent trios using transmission disequilibrium
      test (TDT) and conditional logistic regression models. The minor allele
      frequency, heterozygosity, and a chi test for Hardy-Weinberg equilibrium at each
      SNP were computed between parents. Pairwise linkage disequilibrium was computed
      as both D' and r2 for all SNPs. Both allelic and genotypic TDTs were performed
      for individual SNPs using family-based association test program. Sliding windows
      of haplotypes consisting of 2 to 8 SNPs were tested using haplotype-based
      association test program. Genotypic odd ratios were obtained from conditional
      logistic regression models using STATA software. The family-based TDT using
      individual SNPs and 2- to 8-SNP haplotypes of the gene indicated a significant
      association at rs17104928 (P = 0.014). The haplotype analysis revealed that the
      association was most significant for the haplotype consisting of 3 SNPs
      (rs2073247, rs17104928, and rs17176643; P = 0.007). G/A heterozygote at
      rs17104928 had a significantly increased association with NS-CL/P (genotypic odd
      ratio, 2.88; 95% confidence interval, 1.42-5.84; P = 0.0014, dominant model). The
      high-risk SNP and genotype may provide a better understanding of the etiologic
      role of PAX9 gene in NS-CL/P and potential options for genetic counseling.

PMID- 22976624
TI  - Pediatric facial fractures:  occurrence of concussion and relation to fracture
      patterns.
AB  - BACKGROUND: Children and adolescents with injuries resulting in facial fractures
      are a population that is potentially at risk for suffering concomitant
      concussion. Concussion results in a variety of physical symptoms and often
      affects cognition, emotion, and sleep. These effects can have a significant
      impact on academics and social functioning. Early recognition of concussion and
      active management have been shown to improve outcomes. The goal of this study was
      to describe the occurrence of concussion in patients sustaining facial fractures
      and to determine whether certain fracture types are associated with concussion.
      METHODS: We performed a retrospective review of patients aged 0 to 18 years who
      were evaluated in the emergency department of the Children's Hospital of
      Pittsburgh from 2000 to 2005 with an International Classification of Diseases,
      Ninth Revision code indicative of facial fractures. Data included demographics,
      documentation of concussion, and facial fracture type. Patients with intracranial
      injury were excluded from the study. Univariate chi2 analysis and logistic
      regression were performed to determine characteristics associated with
      concussion. RESULTS: Facial fracture was diagnosed in 782 patients. Ninety-one
      patients had an intracranial injury and were excluded, leaving 691 patients for
      evaluation. The mean age was 11.1 (SD, 4.6) years. Males made up 69.6% of
      patients, and 80.6% of patients were white. Concussion was diagnosed in 31.7% of
      patients. Age, sex, and race were not associated with concussion. Univariate
      analysis demonstrated that skull and orbital fractures were associated with
      higher rates of concussion, whereas maxillary fractures showed a trend toward
      higher rates of concussion, and nasal and mandible fractures showed a trend
      toward lower rates of concussion. Logistic regression analysis demonstrated the
      odds of having a concussion were higher in those with skull fractures (odds
      ratio, 2.3; confidence interval, 1.5-3.7). CONCLUSIONS: Nearly one third of
      pediatric patients with facial fractures in this retrospective series were
      diagnosed with a concomitant concussion. Our data suggest that a higher index of
      suspicion for concussion should be maintained for patients with concomitant skull
      fractures and potentially orbital and maxillary fractures. Given the possibility
      of a worse outcome with delayed concussion diagnosis, patients with facial
      fractures may benefit from more active early concussion screening.

PMID- 22976625
TI  - Management of zygomatic complex residual deformity due to war in Iraq.
AB  - INTRODUCTION: Since March 20, 2003, maxillofacial surgeons in Iraq encounter
      several trauma cases, part of which are zygomatic residual deformities that
      result from conventional war, civil unrest, crimes, and car explosions. This
      study aimed to determine the relationship between etiological factors and
      severity of posttraumatic zygomatic residual deformity and to investigate methods
      of surgical repairs, treatment modalities, and any complications that may have
      occurred during this critical time in Iraq. PATIENTS AND METHODS: There were a
      total of 40 patients with posttraumatic deformity of the zygoma included in this
      study. Records of these patients (29 men and 11 women) who have been treated in
      the maxillofacial unit of a specialized surgery hospital (Medical City Hospital,
      Baghdad) between 2006 and 2011 were collected. RESULTS: Of all patients, 28 (70%)
      had injuries from missile whereas 12 patients (30%) had injuries from other
      causes (aggressive social behavior). According to the causes of delayed
      treatment, 30 patients (60%) were untreated previously (15 patients [50%] of them
      had delay because severe comminution, severe damage, or loss of the overlying
      soft tissue; 3 patients [10%] were undiagnosed; and 12 patients [40%] had
      treatment delayed as a result of major damage to other body parts or medical
      condition), 3 patients (30%) had improper reduction, and 7 patients (70%) had
      improper fixation. Our definitive treatment was as follows: 13 patients (32.5%)
      were treated by osteotomy, 10 patients (25%) were treated by onlay bone graft, 14
      patients (35 %) were treated by both methods, and 3 patients (7.5%) were
      untreated. CONCLUSIONS: [corrected] We recommend that every surgeon who deals
      with residual deformity should clinically evaluate the residual deformity.

PMID- 22976626
TI  - Timing of alveolar bone grafting determines different outcomes in patients with
      unilateral cleft palate.
AB  - The objective of the current study was to assess the outcome of the alveolar bone
      grafting (ABG) in patients with cleft palate. Thirty-one patients with complete
      unilateral cleft lip and palate were prospectively divided into 2 groups
      according to the timing of surgery: (1) secondary ABG (SABG), undertaken during
      mixed dentition (n = 16); and (2) tertiary ABG (TABG), undertaken during
      permanent dentition (n = 15). Septum height was assessed using cone beam computed
      tomography in 3 views (buccal, intermediate, palatal) and classified according to
      the modified Bergland Index, which scores the results into 5 types according to
      the height of the neoformed bone septum (excellent: septum with a normal height;
      good: septum with minor deficiency; regular: marginal defect of >25% of the root
      length; bad: bone deficiency on the nasal aspect; and failure). In the SABG
      group, 6 to 12 months postoperatively, 75% of the patients were classified as
      having excellent/good conditions and 25% as having regular/bad conditions. No
      patients were observed as having failure conditions. In the TABG group, 53% of
      the patients were classified as having excellent/good, 21% were classified as
      having regular/bad conditions, and 26% were classified as having failure
      conditions. Significantly better outcomes were observed for the SABG group when
      compared with the TABG group. In conclusion, the age at which ABG is performed is
      a factor that impacts on the surgical outcome. Specifically, increasing age is
      associated with worse outcomes.

PMID- 22976627
TI  - Does helmet therapy influence the ear shift in positional plagiocephaly?
AB  - BACKGROUND: Helmet therapy is widely accepted in the treatment of severe
      positional plagiocephaly. The improvement of the cranial asymmetry under therapy
      is evident, but parents are also concerned about the ear shift. Our study
      investigated the influence of helmet therapy on the position of the ears and
      analyzed the reliability of clinical observations regarding cranial asymmetry and
      ear shift. METHODS: Three-dimensional stereophotogrammetry of 80 infants with
      severe positional plagiocephaly was performed before and after helmet therapy.
      The cranial vault asymmetry index (CVAI) and ear shift were measured and
      statistically compared. The correlation between the change of CVAI and ear shift
      was investigated. Three surgeons visually evaluated the treatment results on
      three-dimensional images independently with a standard questionnaire. The results
      were compared with the three-dimensional measurements. RESULTS: Sixty infants had
      a relevant initial ear shift. Under therapy, the shift was improved significantly
      by a mean of 29.8% (P < 0.001). Twenty infants with an initial straight ear line
      statistically deteriorate under therapy (P < 0.0001). We found no strong linear
      correlation between the changes of the CVAI and the ear shift. Analysis of the
      questionnaire revealed a good correlation between the clinical impression and
      three-dimensional measurements for the head asymmetry, whereas observations
      regarding changes in the ear shift were not reliable. CONCLUSIONS: Helmet
      treatment significantly improves an initial malposition of the external ear in
      infants with positional plagiocephaly. A severe ear shift can be associated with
      a moderate CVAI and vice versa. In contrast to the CVAI, small changes of the ear
      shift cannot be evaluated reliably by clinical investigation.

PMID- 22976628
TI  - Simultaneous and differential fronto-orbital and midface distraction osteogenesis
      for syndromic craniosynostosis using rigid external distractor II.
AB  - In syndromic craniosynostosis, the relation between the supraorbital area and the
      frontal bone is not good, and it is not possible to reform this area with 1-block
      advancement. To avoid this problem, the frontal bone is separated from the fronto
      orbital bandeau, each is reshaped and remodeled separately, and then both are
      reattached. The retrusion of the midface, especially in syndromic
      craniosynostosis, is usually greater than that of cranial bones, so the technique
      usually separating the midface from the cranium is Le Fort III osteotomy, which
      allows differential distraction of each part. In this procedure, the cranial and
      midfacial bones are advanced simultaneously and differentially, both to the
      planned extent, in a single-stage operation, using rigid external distractor II,
      correcting exorbitism, respiratory embarrassment, and cranial structures and
      avoiding eye complications in the future. This procedure was used, with a follow
      up, in 10 patients with syndromic craniosynostosis from 2 to 5 years.

PMID- 22976629
TI  - Blood loss estimation during fronto-orbital advancement:  implications for blood
      transfusion practice and hospital length of stay.
AB  - BACKGROUND: Reliable measurement of intraoperative blood loss remains a serious
      challenge during correction of craniosynostosis. This study analyzed the
      relationship between estimated blood loss (EBL) and calculated blood loss (CBL)
      in fronto-orbital advancement and its implications on blood transfusion practice
      and hospital length of stay (LOS). METHODS: The authors reviewed infants who
      underwent primary fronto-orbital advancement for craniosynostosis (1997-2009).
      Estimated blood loss was based on anesthesia records and CBL by
      preoperative/postoperative hemoglobin. Perioperative red blood cell transfusion
      (RCT) and hospital LOS were recorded. RESULTS: Ninety infants were included. Mean
      EBL was 42.2% of estimated blood volume (% EBV), and CBL was 39.3% EBV, without
      significant difference (P = 0.23). Bland-Altman analysis revealed that EBL was
      greater than CBL at lower levels of blood loss (<=47.0% EBV) and less than CBL at
      higher levels (>47.0% EBV). Mean intraoperative RCT was 45.8% EBV;
      overtransfusion was more frequent at lower levels of bleeding, and
      undertransfusion at higher levels. Postoperative RCT occurred more frequently
      with greater blood loss. Mean LOS was 3.7 days, increasing with CBL (hazard ratio
      of discharge, HR(discharge) = 0.988, P < 0.01), postoperative RCT (HR(discharge)
      = 0.96, P < 0.05), total RCT (HR(discharge) = 0.991, P < 0.05), and total
      intraoperative fluid (HR(discharge) = 0.999, P < 0.05). CONCLUSIONS: Estimated
      blood loss is a less accurate marker for CBL at the extremes of blood loss during
      fronto-orbital advancement. The tendency to overestimate blood loss with less
      intravascular volume loss can result in unnecessary transfusion, whereas
      underestimation with greater actual blood loss can lead to delay in resuscitation
      and longer hospitalization.

PMID- 22976630
TI  - Effect of autologous platelet-rich plasma in combination with a biphasic
      synthetic graft material on bone healing in critical-size cranial defects.
AB  - PURPOSE: The aim of the study was to investigate the effect of autologous
      platelet-rich plasma (PRP) on the osteogenic potential of a biphasic synthetic
      graft material composed of hydroxyapatite and beta-tricalcium phosphate (HA/beta
      TCP) in critical-size cranial defects in rabbits. MATERIALS AND METHODS: Three
      circular bicortical critical-size cranial defects were created in each of 18
      rabbits. The first of the defects was grafted with autologous PRP and HA/beta
      TCP, the second was grafted with HA/beta-TCP without PRP, and the third was left
      unfilled as a negative control. Animals were euthanized at 2, 4, and 6 weeks
      after surgery. Harvested tissue specimens were evaluated histologically and
      histomorphometrically. Several parameters associated with osteoclastic and
      osteoblastic activities were measured and calculated. The results were
      statistically analyzed using the 1-way analysis of variance statistical method.
      RESULTS: Histologic analysis of the samples showed bone tissue formation at all
      experimental sites including untreated control defects. A statistically
      significant difference in new bone formation between the defects treated with
      HA/beta-TCP + PRP and defects treated with HA/beta-TCP alone was not observed.
      Control untreated defects showed the greatest bone regeneration. CONCLUSIONS: In
      this animal model, autologous PRP had no effect on bone healing in addition to a
      biphasic HA/beta-TCP synthetic graft material after 2, 4, and 6 weeks of
      implantation.

PMID- 22976631
TI  - Rhinoplasty in the Black Sea Region.
AB  - We have retrospectively evaluated the charts of 120 patients who had undergone
      rhinoplasties. The noses were divided into 2 types. Type 1 (42 cases) was
      characterized by a normal radix, high dorsum, and prominent vault. These noses
      were corrected by dorsal reduction, lateral osteotomy when needed, and caudal
      septal resection. Type 2 (78 cases) was characterized by a dependent tip with
      inadequate projection and a low radix with an excessive projected dorsal hump.
      These noses were corrected by tip support with cartilage graft and/or various
      suturing techniques and dorsal reduction. Secondary revision was necessary in 26
      patients (21.6% of the total number) mostly due to inadequate septal correction
      in the first operation and irregularities of the dorsum. The postoperative result
      was considered as good in 88 (81%), fair in 27 (15%), and poor in 5 (4%) by the
      patients. Although the cases presented in this series were mostly difficult ones,
      experience was found to be the major determinant in success while dealing with
      the challenging noses of the Black Sea Region.

PMID- 22976632
TI  - Quantification of retropalatal region in obstructive sleep apnea.
AB  - OBJECTIVE: Flexible optic laryngoscopy (FOL) allows us to visualize the
      obstructive sleep apnea (OSA)-related airway passages. However, objective data
      presenting evidence of OSA through this perspective are lacking. The aim of this
      study was to quantify the surface area of the retropalatal region in control
      subjects and OSA patients utilizing FOL images. This was a prospective, case
      control study. The study was performed at the otolaryngology department of a
      university hospital. SUBJECTS AND METHODS: Sixty-seven OSA patients in group 1
      and 87 patients with no complaints of OSA in group 2 were evaluated. Retropalatal
      region photographs were captured at the base of uvula through endoscopic images.
      The retropalatal surface area (RPSA) was measured using AutoCAD. Groups 1 and 2
      RPSA measurements were analyzed. The RPSA measurements of subgroups in group 1
      were analyzed to document severity of OSA. RESULTS: Mean RPSA measurements in
      group 1 was 73.21 (SD, 31.99), and that in group 2 was 129.31 (SD, 26.54),
      respectively. Retropalatal surface area is significantly larger in group 2 when
      compared with group 1 (P = 0.0001). Twenty-four patients had mild (mean
      respiratory disturbance index [RDI], 10.83 [SD, 3.63], 26 had moderate (mean RDI,
      20.9 [SD, 4.14]), and 17 had severe OSA (mean RDI, 52.13 [SD, 17.24]) in group 1.
      The mean RPSA measurements are 72.48 (SD, 28.9) in mild subgroup, 73.88 (SD,
      30.5) in moderate subgroup, and 73.22 (SD, 39.59) in severe subgroup, showing no
      evidence of correlation between the severity OSA and RPSA measurements.
      CONCLUSIONS: The RPSA measurements are significantly larger in control subjects
      (group 2) when compared with OSA patients (group 1). This might implicate that
      RPSA measurements through FOL examination can be a predictor of OSA when
      screening patients.

PMID- 22976633
TI  - Soft tissue changes after orthodontic surgical correction of jaws asymmetry
      evaluated by three-dimensional surface laser scanner.
AB  - Aesthetic improvement is an essential goal of treatment of facial asymmetry, and
      it is often difficult to achieve. Reliable three-dimensional measurements are
      required to support outcome studies. In this study, 15 white adult subjects, 9
      females and 6 males, with maxillomandibular asymmetry and malocclusion were
      studied. The patients were treated with orthodontics and different surgical
      procedures in single or multiple steps. All patients received double-jaw surgery,
      except 1 patient who underwent only maxillary osteotomy. Nine of the 15 patients
      received additional procedures (genioplasty and rhinoplasty) to achieve better
      symmetry. Posterior-anterior and lateral cephalometry and three-dimensional
      facial surface data were obtained before (T0) and 1 year (T1) after surgery. Scan
      data at T0 and T1 were pooled by electronic surface averaging to obtain the mean
      pretreatment and posttreatment facial model. A symmetric model was constructed by
      averaging the actual T0 scans and their mirrored models to obtain the virtual
      optimal symmetric face. Different linear and angular measurements were then
      calculated for comparison of the mean T0 and T1 models. The normalization of
      facial proportion and a high increase in symmetry were evident. Residual defects
      were documented in the postoperative symmetry of the chin. Treatment of facial
      asymmetry, combined with dental occlusion problems, is still a challenge for
      maxillofacial surgeons. Orthognathic surgery provides an important improvement of
      symmetry, but further refinements of technique are still required. Three
      dimensional evaluation results in an effective method to support outcome studies
      on the surgical correction of complex facial deformities.

PMID- 22976634
TI  - Topography of the submental artery that should be considered in bleeding during
      dentoalveolar surgery.
AB  - The purpose of the present study was to provide precise data regarding the
      branching pattern of the submental artery, which should be considered in
      occasions of bleeding during various dentoalveolar surgical procedures of the
      mandible, such as implant surgeries, tori removal, and iatrogenic injuries.
      Twenty-six embalmed adult hemifaces from Korean cadavers were used in this study.
      The vertical distance, horizontal distance, and diameter of the submental artery
      were measured from the site of the first premolar to the third molar. In cases
      where there was penetration of the mylohyoid muscle by the main branches of the
      submental artery, the same items were measured at that point. The vertical
      distance between the submental artery and the inferior border of the mandible
      decreased toward the premolar, whereas the horizontal distance from the lingual
      plate of the mandible increased gradually as it traveled in the anterior
      direction. The diameter of the artery narrowed slightly toward the premolar. The
      main branches of the submental artery perforated the mylohyoid muscle in 14 (54%)
      of the 26 specimens. As a result of this study, the submental artery is located
      higher from the inferior border and closer to the lingual plate of the mandible
      in the region of the molar than that of the premolar. Therefore, clinicians
      should be more careful of bleeding when performing surgery in the molar region
      compared with the premolar region. Where the mylohyoid muscle is perforated by
      the main branches of the submental artery, its point of insertion can be observed
      in diverse locations.

PMID- 22976635
TI  - Puncture of foramen ovale cranium in computed tomography three-dimensional
      reconstruction.
AB  - The study aimed to provide the anatomic data for puncture of foramen ovale
      cranium in oral cavity. We scan 100 volunteers' skull on computed tomography who
      have no lesion of skull base, of which the images were for three-dimensional
      reconstruction. The following observations and measurements were carried out: the
      shape, size of foramen ovale cranium, and the angle and length of puncture line.
      The results we got are the following: foramen ovale cranium appears as oval,
      kidney shape, round, pear shape, and strip shape. Foramen ovale diameter is 8.20
      +/- 1.54 mm, and width is 4.08 +/- 0.73 mm for men and 4.23 +/- 0.79 mm for
      female. The distance from the center of foramen ovale to the maxillary second
      molar is 51.65 mm for male and 48.77 mm for female. The puncture line is from the
      center of foramen ovale to the maxillary second molar. The angle of the puncture
      line with the vertical plane, which is through the midpoint of supraorbital
      margin and the infraorbital margin, is 40.27 degrees for men and 37.31 degrees
      for women. The angle of the puncture line with the horizontal plane is 49.37
      degrees for men and 52.26 degrees for women. The angle of the puncture line with
      the sagittal plane is 3.78 degrees. All data between the left and right sides
      have no statistically significant difference (P > 0.05), but the diameter, the
      length of the puncture, and the angle of puncture line with the horizontal and
      vertical have significant differences on sex (P < 0.01). The anatomic character
      of the foramen ovale cranium has important value on the accuracy of puncture for
      the treatment of trigeminal neuralgia.

PMID- 22976636
TI  - Analysis of ethmoid roof and skull base with coronal section paranasal sinus
      computed tomography.
AB  - Chronic paranasal sinus disease is one of the most common causes of application
      to physicians in pediatric and adult patients. In the surgical treatment of these
      diseases, endoscopic sinus surgery is an application that is often done to
      increase the quality of the patient's life. On account of this, the anatomic
      variations in skull basement must be well known to avoid possible major
      complications that may occur during the operation. Recent developments in
      paranasal sinus surgery also enhanced the need for examining exhaustively the
      anatomy of this region and existing pathology. Superiority of computed tomography
      (CT) has an unquestionable importance for the evaluation of anatomic structure
      and pathology compared with conventional radiographs. A likely anatomic knowledge
      is needed for a safe surgery. Before the surgery, determining the anatomic
      variations makes the operation safer and increases the prospects, so we can
      prevent complications that may occur during the surgery. In this study, CT
      coronal sections of 300 patients who were admitted to the Department of Ear Nose
      Throat of Medical Faculty of Cumhuriyet University Research and Training Hospital
      between the dates December 2008 and January 2011 with complaints of nasal flow
      and postnasal drip were studied. According to coronal section CT examinations,
      the patients were divided into 2 groups. Group 1, with 156 cases (64%), showed
      mucosal changes, and in 144 cases (36%), no mucosal changes were established
      (group 2). In comparison between the sexes, in groups 1 and 2 females,
      significant difference was determined for other parameters except the average
      height of the ethmoid roof. In the comparison between the sexes, in groups 1 and
      2 males, significant difference was determined for all parameters. The difference
      between these 2 rates was statistically significant. Keros types 1 and 2 cases
      were compared with the control group, and there was no statistically significant
      difference. Notwithstanding, at the comparison of the Keros type 3 with the
      control group, there was a statistically significant difference for all the
      parameters (maximum orbital height, the length of the middle concha, and the
      nasal wall). It seems to be important for us to know the average length of the
      peripheral anatomic structures to avoid serious complications that may occur
      during the operation. Careful preoperative review of paranasal sinus CT scans in
      patients undergoing sinus surgery seems to be the most important to prevent
      severe intraoperative complications.

PMID- 22976637
TI  - Radiologic assessment of the relationship between the maxillary artery and the
      lateral pterygoid muscle.
AB  - OBJECTIVE: The course of the second part of the maxillary can vary among
      different races. The aim of this study was to evaluate the relation between the
      maxillary artery and the lateral pterygoid muscle in a white population sample on
      computed tomographic (CT) angiograms. MATERIALS AND METHODS: We retrospectively
      reviewed multidetector CT angiograms of 209 patients (134 men and 75 women). The
      images were taken using a 64-row multidetector CT scanner. The imaging parameters
      were 0.5 * 64-mm slice thickness, 0.5- or 0.3-mm increment, 120 kV, 250 mA s, 0.5
      second rotation time, 0.641 pitch, and 512 matrix. The relationship between the
      pterygoid portion of the maxillary artery and the lateral pterygoid muscle was
      assessed on axial, sagittal, and coronal multiplanar reformatted images with the
      Vitrea 2 software program. RESULTS: A total of 572 maxillary arteries in 286
      patients were assessed. Of these maxillary arteries, 418 (68.42%) had a
      superficial course to the pterygoid muscle and 132 (31.58%) had a deep course. In
      165 (78.94%) of 286 patients, there was a cross-lateral symmetry of the course of
      the artery; that is, both vessels were superficial or deep. In 44 (21.1%) of 209
      patients, an asymmetric course was observed. CONCLUSIONS: Because of the
      incidence of the asymmetric presentations, generalization regarding such a
      controversial topic should not be based on findings of cadaveric studies and each
      hemi head should be considered as a single entity. Therefore, advanced imaging
      systems are useful tools in preoperative planning and play a key role in the
      avoidance of hemorrhagic complications.

PMID- 22976638
TI  - Extradural subtemporal transzygomatic approach to the clival and paraclival
      region with endoscopic assist.
AB  - The authors describe the extradural subtemporal transzygomatic (ESTZ) approach
      and its variants to expose the clival and paraclival areas. A microanatomical
      study was conducted to quantify the clival and paraclival exposure and the
      maneuverability areas obtained by microscope and endoscope using the ESTZ
      approach. Section versus preservation of the third trigeminal branch (V3) and
      petrous apicectomy to obtain a wider clival exposure and a better internal
      carotid artery control are discussed. Eight cadaveric specimens were dissected to
      obtain morphometric measurements after performing the ESTZ approach and its
      variants. Anatomic areas exposed by the approaches were calculated using the
      ImageJ 1.37a software. The ESTZ approach performed with sectioning of V3 and
      petrous apicectomy allowed for a mean incremental exposed area of 1.8 cm2 (range,
      1.24-2.43 cm2). The mean amount of additional anatomic areas visualized after the
      ESTZ approach with petrous apicectomy if compared with the ESTZ approach without
      petrous apicectomy was 24% (range, 14.4%-37.5%). The mean percentage increase of
      maneuverability area after petrous apicectomy was 69.9% (range, 43.8%-96.6%). The
      ESTZ approach is suitable when dealing with extradural tumors of the middle-upper
      clivus extending into the ipsilateral paraclival area. V3 section and petrous
      apicectomy increase the operability, the surgical exposure, and the
      maneuverability area and improve vascular control on the internal carotid artery.
      Application of endoscopy does not impact on the maneuverability area but enhances
      the visualization of blind corners; endoscopic surgical view without drilling the
      petrous apex is comparable to that obtained by the microscope after petrous
      apicectomy.

PMID- 22976639
TI  - Levator sheath revisited.
AB  - The aim of this study was to reconfirm the detailed histologic structure of the
      levator aponeurosis and superior transverse ligament, which were first described
      by Whitnall. Twenty-eight upper eyelids from 28 Korean adult cadavers (mean age,
      79.5 [SD, 11.3] years; 16 males and 12 females) were used. Sagittal sections on
      the midpupillary line were made, and 10-MUm-thick sections were prepared. Twenty
      five were stained with Masson trichrome, and 16 were prepared for
      immunohistochemical staining for smooth muscle fibers using mouse monoclonal anti
      smooth muscle Ab. The levator palpebrae superioris muscle was covered with its
      fascial sheath along its course. The superficial part of the fascia sheath that
      covered the upper aspect of the levator palpebrae superioris just behind the
      aponeurosis was condensed to form a definite ligamentous band. In front of this
      ligamentous condensation, the sheath becomes abruptly so thin that it appears to
      end in a free border, but it could be traced forward as a very delicate layer up
      to the supratarsal border. The orbital septum consisted of 2 layers. The whitish
      outer (superficial) layer descends to interdigitate with the levator aponeurosis
      with loose connective tissue, and then it disperses inferiorly. The inner (deep)
      layer initially follows the superficial one, and then it reflects at the levator
      aponeurosis and continues posteriorly with the levator sheath. In most of the
      specimens, the levator aponeurosis consisted of a single layer in 27 (96.4%) of
      28 eyelids. Only 1 eyelid has been observed to show a double-layered levator
      aponeurosis (3.6%). Some immunostained smooth muscle fibers in the lower side of
      the levator aponeurosis ran along its entire course. We reconfirmed the levator
      sheath covering the levator aponeurosis, and it continued anteriorly with the
      inner layer of the orbital septum, as Whitnall described. This information will
      be helpful when performing upper eyelid surgeries.

PMID- 22976640
TI  - Neuropeptide expression and T-lymphocyte recruitment in facial nucleus after
      facial nerve axotomy.
AB  - Axonal injury in the peripheral nervous system can have a strong impact on the
      neurons and the surrounding non-neuronals cells. The aim of this study was to
      evaluate the immunohistochemistry signals of the vasoactive intestinal peptide
      (VIP), substance P (SP), and CD3+ T cells and the messenger RNA levels of
      neuropeptides in the facial nucleus (FN) at 7, 14, and 21 days after peripheral
      facial nerve axotomy. Moreover, the authors assayed the peripheral blood levels
      of interleukin (IL-1beta), tumor necrosis factor-alpha, and IL-6 serum levels at
      24 and 48 hours after the surgical procedures. Immunohistochemistry analysis
      revealed that VIP and SP expression is strongly induced in FN after peripheral
      facial nerve axotomy at 7 days, the CD3+ pan-T cells peak at 14 days. Polymerase
      chain reaction analysis for VIP and SP messenger RNA levels confirms the
      immunohistochemical data, but VIP level remains significantly high for 14 days.
      The serum level of IL-6 48 hours after axotomy was significantly higher than
      after 24 hours; there were no significant changes for IL-1beta and tumor necrosis
      factor-alpha serum levels between 24 and 48 hours. Our data reveal that FN
      neurons are under neuropeptidergic influence and show that
      modulation/modification of VIP and SP expression in FN injury models facilitates
      the crossing of the blood-brain barrier. On the contrary, our results emphasize
      the role of the T cells in preventing initial neurodegeneration or neuronal
      death. The high serum levels of IL-6 at 1 to 2 days suggest that this cytokine
      could play a central role in the initiation of immunosurveillance and provide
      advance information on the recruitment of CD3+ T lymphocytes in the FN.

PMID- 22976641
TI  - Morphometric study of mandibular ramus related to sagittal ramus split osteotomy
      and osteosynthesis.
AB  - The objective of this study was to quantify the cortical bone thickness of the
      mandibular ramus to determine conditions related to sagittal split ramus
      osteotomy and placement of screws. The patient sample comprised 44 subjects of
      ages ranging from 46 to 52 years (mean age, 49 years). The cone-beam computed
      tomography was performed and realized 3 cuts in the third molar area (section A),
      5 mm posterior (section B), and 5 mm posterior to the latter (section C).
      Measurement in the cortical areas of the superior and inferior levels related to
      mandibular canal and measurement related to the total width of the mandible was
      executed. Intraclass correlation coefficient with P < 0.05 was used. The result
      showed that the buccal and lingual cortical zone did not present statistical
      differences, and the minor value was 1.5 mm for each one. There were no
      differences in the superior and inferior cortical bone, and the total width of
      the mandible was between 15.9 and 8.5 mm in the anterior area, between 17.4 and
      12.8 mm in the middle area, and between 18 and 8.8 mm in the posterior area. The
      distance superiorly to the mandibular canal presented a minimal SD with a mean of
      8.5 mm in the anterior region, 10.6 mm for the middle region, and 12.5 mm in the
      posterior region. In conclusion, the cortical thickness of the mandibular ramus
      in the adult population is particularly strong and offers a good anchorage for
      screw insertion in sagittal split ramus osteotomy.

PMID- 22976642
TI  - Location of the mandibular branch of the facial nerve according to the neck
      position.
AB  - The aim of this study was to elucidate the exact location of the mandibular
      branch of the facial nerve according to different neck positions. Twenty-two
      hemifaces of 11 fresh human cadavers were used (age range, 53-89 y; mean age,
      72.3 +/- 10.5 y; 8 men and 3 women). Working through skin windows, the distance
      from the mandibular border to the mandibular branch of the facial nerve (border
      nerve distance or BND) was measured at 3 points: (1) the mandible angle (gonion
      or Go point), (2) the point where the mandibular branch of the facial nerve
      crosses the facial artery (FA point), and (3) the one-fourth point from the
      gonion to the menton (1/4 point). Threads were hung on the skin windows along the
      mandibular border. With the neck in the neutral position and then full flexion
      (15 degrees), extension (15 degrees), and left and right rotations (30 degrees),
      the distance of the mandibular branch from the thread of the mandibular border
      was measured using calipers. In the neutral position, the mandibular branch was
      3.50 +/- 2.82 mm above the mandibular border at the Go point, 5.34 +/- 2.98 mm
      above the mandibular border at the FA point, and 5.28 +/- 1.86 mm above the
      mandibular border at the 1/4 point. At all 3 points, flexion or extension of the
      neck did not significantly move the mandibular branch. At the Go point and FA
      point, there was no significant difference between the ipsilateral rotation
      position and the contralateral rotation. Yet at the 1/4 point, the BND decreased
      (4.32 +/- 2.60 mm) with the neck in ipsilateral rotation and the BND increased
      (5.97 +/- 2.62 mm) with the neck in contralateral rotation. There was a
      significant difference between the ipsilateral rotation position and the
      contralateral rotation position (P = 0.020, t-test). Surgeons should keep in mind
      that at the 1/4 point, the mandibular branch of the facial nerve moves downward
      1.10 +/- 1.42 mm with the neck in ipsilateral rotation and moves upward 0.49 +/-
      1.84 mm with the neck in contralateral rotation.

PMID- 22976643
TI  - Maximum forces applied to the orbital floor after fractures.
AB  - The objective of this study was to measure the force on and displacement of
      completely detached intraorbital tissue from the bony orbit, as a worst-case
      scenario after orbital trauma, to preserve the maximum load and predict the
      necessary strength of reconstruction materials. Six fresh-frozen human heads were
      used, and orbital floor defects in the right and left orbits were created by the
      direct impact of 3.0 J onto the globe and infraorbital rim. The orbital floor
      defect sizes and displacements were evaluated after performing a Le Fort I
      osteotomy. In addition, after the repositioning of the completely detached
      intraorbital tissue, the forces and displacements were measured. The mean orbital
      floor defect sizes were 208.3 (SD, 33.4) mm2 for globe impacts and 221.8 (SD,
      53.1) mm2 for infraorbital impacts. The mean intraorbital tissue displacement
      after the impact and before repositioning was 5.6 (SD, 1.0) mm for globe impacts
      and 2.8 (SD, 0.7) mm for infraorbital impacts. After repositioning, the
      displacements were 0.8 (SD, 0.5) mm and 1.1 (SD, 0.7) mm, respectively. The
      measured forces were 0.10519 (SD, 0.00958) N without the incorporation and
      approximately 0.11128 (SD, 0.003599) N with the incorporation of reconstruction
      materials. The maximum forces on the completely detached orbital tissue were
      minimal (~0.11 N) and suggest the use of collagen membranes as reconstruction
      materials for orbital floor defects, at least in medium-sized fractures.

PMID- 22976644
TI  - Effect of calvarial burring on resorption of onlay cranial bone graft.
AB  - Variable resorption occurs whenever calvarial bone graft is used for onlay
      cranioplasty. The recipient ectocortex may be burred to expose vessels and
      osteocytes to maximize healing. The purpose of this study was to determine
      whether abrading the recipient site improves the volume of onlay graft. The
      parietal bones of 17 rabbits were sectioned into split-thickness and full
      thickness grafts. The right frontal cortex was abraded with a bur to punctate
      bleeding. Pairs of split-thickness (n = 48) or full-thickness (n = 20) grafts
      were onlayed to the burred right frontal bone and to the nonburred left frontal
      bone. Micro-computed tomography was used to determine graft volume immediately
      postoperatively and 16 weeks later. Histology, including tartrate-resistant acid
      phosphatase staining, was performed to quantify vascular channels and osteoclasts
      per high-power field 10 days postoperatively. Split-thickness graft volume
      decreased 58.0% when placed on the burred calvarial site, compared with grafts on
      the nonburred cortex (28.4%) (P = 0.01). Full-thickness grafts showed a similar
      trend: greater resorption (39.1%) when onlayed onto abraded calvaria compared
      with nonburred ectocortex (26.0%) (P = 0.11). Split-thickness graft orientation
      (cortical vs cancellous side in contact with the recipient site) did not affect
      resorption (P = 0.67). Onlay grafts placed on the burred recipient site had more
      vascular channels (11.8) and osteoclasts (5.7), compared with grafts over
      nonabraded cortex (3.4 and 4.2, respectively) (P < 0.05). Burring the recipient
      site cortex before onlay cranial bone grafting promotes resorption, possibly by
      increasing vascularization and osteoclastic activity. This technique cannot be
      recommended.

PMID- 22976645
TI  - Reharvested cranial particulate bone graft ossifies inlay calvarial defects.
AB  - Particulate bone graft (PBG) heals calvarial critical-size defects and is
      procured from the cranium with a hand-driven bit and brace. The donor sites
      ossify, and thus PBG potentially could be reharvested from the original areas.
      The purpose of this study was to determine if PBG obtained from a healed donor
      site is effective for inlay cranioplasty. A 17 * 17-mm critical-size defect was
      created in the parietal bones of 8 rabbits and treated with either no implant
      (group 1) or PBG harvested from the frontal bone (group 2). In 4 animals (group
      3), a parietal defect was not created initially; PBG was harvested from the
      frontal bone and then discarded. Sixteen weeks later after the PBG donor sites
      had healed, a 17 * 17-mm parietal defect was made and filled with PBG reharvested
      from the previous donor area. Animals underwent micro-computed tomography 16
      weeks after inlay cranioplasty. Critical-size defects in controls (group 1)
      exhibited partial ossification (35.1% +/- 10.5%) compared with those treated with
      PBG (group 2) (99.1% +/- 1.5%) or reharvested PBG (group 3) (99.3% +/- 1.5%) (P =
      0.02). No difference was found between groups 2 and 3 (P = 0.69). Bony thickness
      was similar in defects implanted with PBG (1.8 mm +/- 1.1 mm) or reharvested PBG
      (2.1 mm +/- 0.5 mm) (P = 0.68). Particulate bone graft reharvested from healed
      donor sites ossifies inlay cranial defects. Because the donor area for PBG is of
      partial thickness and less than critical size, reparative osteogenesis
      theoretically allows an unlimited supply of autologous bone for inlay
      cranioplasty using PBG.

PMID- 22976646
TI  - Quantifying mineralization using bone mineral density distribution in the
      mandible.
AB  - BACKGROUND: Micro-computed tomography is an efficient method for quantifying the
      density and mineralization of mandibular microarchitecture. Conventional
      radiomorphometrics such as bone and tissue mineral density are useful in
      determining the average overall mineral content of a scanned specimen; however,
      relying solely on these metrics has limitations. Using bone mineral density
      distribution (BMDD), the complex array of mineralization densities within a bone
      sample can be portrayed. This information is particularly useful as a
      computational feature reflective of the rate of bone turnover. We demonstrate the
      utility of BMDD analyses in the rat mandible and generate a platform for further
      exploration of mandibular pathology and treatment. METHODS: Male Sprague-Dawley
      rats (n = 8) underwent micro-computed tomography, and histogram data were
      generated from a selected volume of interest. A standard curve was derived for
      each animal, and reference criteria were defined. An average histogram was
      produced for the group, and descriptive analyses including the means and SDs are
      reported for each of the normative metrics. RESULTS: M(peak) (3444 Hounsfield
      units [SD, 138]) and M(width) (2221 Hounsfield units [SD, 628]) are 2 metrics
      demonstrating reproducible parameters of BMDD with minimal variance. A total of 8
      valuable metrics quantifying biologically significant events concerning
      mineralization are reported. CONCLUSIONS: We quantify the vast wealth of
      information depicted in the complete spectrum of mineralization established by
      the BMDD analysis. We demonstrate its potential in delivering mineralization data
      that encompass and enhance conventional reporting of radiomorphometrics.
      Moreover, we explore its role and translational potential in craniofacial
      experimentation.

PMID- 22976647
TI  - Creep analysis of PLLA: PGA copolymer craniofacial plates.
AB  - Bioabsorbable fixation device failures occur clinically on occasion, with
      failures often brittle in nature. However, creep failure may also occur for
      implants that are subjected to sustained loads whereby the device may slowly
      deform over time, perhaps leading to fracture. Even without fracture occurring,
      the device may become too distorted to function. There is little in the
      literature regarding creep performance of bioabsorbable devices such as plates
      and screws. This study investigated the creep characteristics of craniofacial
      plates and screws made of a copolymer of 82% poly-L-lactic acid and 18%
      polyglycolic acid. Four-hole straight plates were attached to 2 rectangular
      portions of synthetic bone substrate using 2.0-mm-diameter bioabsorbable screws
      (2 screws used to attach the plate to each substrate portion). The constructs
      were submersed in phosphate-buffered saline (pH 7.4, 37 degrees C) and placed in
      tension with 3 load configurations, that is, 230, 460, and 1140 g, for at least 6
      days. Creep rate was constant at a given load and was directly proportional to
      load (4.7, 14.3, and 33.3 MUm/h for 230-, 460-, and 1140-g loads, respectively).
      The data conformed well to basic creep theory analysis and provided an estimate
      of the absolute viscosity of the polymer of 8.7 * 10(12) +/- 0.81 * 10(12) P
      (average +/- SEM), which is intermediate between that of soft and hard tissue,
      although closer to the latter. Surgeons and engineers should be aware of the
      potential for creep to occur when designing bioabsorbable implants and
      investigating new clinical applications.

PMID- 22976648
TI  - Effect of intraoperative platelet-rich plasma and fibrin glue application on skin
      flap survival.
AB  - The experiment was designed to compare the effect of intraoperative platelet-rich
      plasma (PRP) and fibrin glue application on skin flap survival. In this study,
      bilateral epigastric flaps were elevated in 24 rats. The right-side flaps were
      used as the control of the left-side flaps. Platelet-rich plasma, fibrin glue,
      and thrombin had been applied under the flap sites in groups 1, 2, and 3,
      respectively. Five days later, all flap pedicles were ligated. Necrotic area
      measurements, microangiography, and histologic and immunohistochemical
      evaluations were performed to compare the groups. Platelet-rich plasma reduced
      necrotic area percentages as compared with other groups. Histologically and
      microangiographically increased number of arterioles were observed in PRP groups.
      Thrombin when used alone increased flap necrosis. Vascular endothelial growth
      factor, platelet-derived growth factor, and transforming growth factor beta3
      primary antibody staining showed increased neovascularization and
      reepithelialization in all PRP-applied flaps. This study demonstrated that PRP,
      when applied intraoperatively under the skin flap, may enhance flap survival.
      Thrombin used alone was found to be unsuitable in flap surgery.

PMID- 22976649
TI  - Comparison of early fibrovascular proliferation according to orbital implant in
      orbital floor fracture reconstruction.
AB  - BACKGROUNDS: Although reports of successful treatment results of orbital
      fractures are numerous, histopathologic changes associated with favorable
      outcomes have not yet been established. The purpose of this study was to observe
      fibrovascular ingrowth into implants, fibrovascularization, and inflammatory
      reactions in surface tissues of implants in an animal model of orbital floor
      fractures. METHODS: Twenty-four New Zealand white rabbits were used in the study.
      A standardized 6-mm-diameter defect was made bilaterally in the maxillary sinuses
      to include bone and mucosa, and an 8 * 8-mm alloplastic implant was inserted. In
      the control group, a bone defect was made, but no implant was inserted. Two
      different implant materials 1 mm in width were used: porous high-density
      polyethylene (Medpor, group A) and absorbable copolymer (Macropore, group B). The
      implants were harvested at 1, 2, and 6 weeks after implantation. Hematoxylin
      eosin stains and immunohistochemical studies of basic fibroblast growth factor
      (bFGF) and CD31 (platelet/endothelial cell adhesion molecule) were conducted.
      RESULTS: Full-thickness fibrovascular ingrowth into the implants was observed in
      group A after 2 weeks, but there was no fibrovascular ingrowth into the implant
      in group B. The inflammatory reactions between the implant and the connective
      tissue were grade 2 at 1 week and grade 1 at 2 and 6 weeks in both groups. The
      bFGF indexes in fibrovascular tissue growing into the nonabsorbable porous
      polyethylene implants (group A-1) were 0.3 at 1 week, 2.3 at 2 weeks, and 3.0 at
      6 weeks. The bFGF indexes at the surface tissues of the implant in the
      nonabsorbable porous polyethylene implants (Medpor, group A-2) and group B were
      1.0 and 1.8 at 1 week, 2.5 and 2.8 at 2 weeks, and 3.0 and 3.0 at 6 weeks.
      Expressions of CD31 in group A-1 were 3.8 at 1 week, 6.0 at 2 weeks, and 20.3 at
      6 weeks. Expressions of CD31 in group A-2 and group B were 19.8 and 23.3 at 1
      week, 38.0 and 49.3 at 2 weeks, and 64.3 and 72.0 at 6 weeks. CONCLUSIONS:
      Because there was no fibrovascular ingrowth into the absorbable copolymer
      implant, such implants may be advantageous in orbital wall fractures with
      exposures of extraocular muscle. However, the possibility of migration and
      extrusion of the implant cannot be excluded because there was no fibrovascular
      ingrowth into the absorbable copolymer implants. Therefore, nonabsorbable porous
      polyethylene implants are better suited for use in orbital wall fractures when
      there is concern about implant migration and extrusion during the early
      postoperative period and large orbital wall fractures.

PMID- 22976650
TI  - Effects of sympathetic innervation loss on mandibular distraction osteogenesis.
AB  - Sympathetic nerve system has been proved to have important regulative effects to
      bone mass. However, the role of sympathetic nerve system in distraction
      osteogenesis (DO) is unclear. Here we show that the sympathetic nerve system
      plays an important role in mandibular DO. Thirty male Sprague-Dawley rats were
      divided into 2 groups at random. Right-side mandibular DO was performed on the 15
      rats in control group (group A). Bilateral transection of cervical sympathetic
      trunk and right-side mandibular DO were performed on the 15 rats in the
      experimental group (group B). After operation, quantitative general observations,
      micro-computed tomography bone morphology analysis, and hematoxylin-eosin
      staining osseous tissue on new osteotylus in distraction gap were performed at
      consolidation time of 1, 14, and 28 days. SPSS 12.0 software package was used for
      statistical analysis. At 1 and 14 days of consolidation time, there was more
      continuous bone formation in the experimental group than that of the control
      group as determined by gross observation. Bone formation parameters including
      bone mineral density, bone volume-total volume ratio, bone trabeculae number as
      determined by micro-CT, and histological study of the test group were
      significantly higher than those of the control group (P < 0.05). No significant
      difference was noted between the 2 groups on consolidation time of 28 days. Our
      study suggested that the sympathetic innervation loss could improve mandibular DO
      and new bone formation, and the sympathetic nerve system might negatively
      regulate the process of DO.

PMID- 22976651
TI  - In vitro quantification of strain patterns in the craniofacial skeleton due to
      masseter and temporalis activities.
AB  - Many complications in craniofacial surgery can be attributed to a lack of
      characterization of facial skeletal strain patterns. This study aimed to
      delineate human midfacial strain patterns under uniform muscle loading. The left
      sides of 5 fresh-frozen human cadaveric heads were dissected of all soft tissues
      except the temporalis and masseter muscles. Tensile forces were applied to the
      free mandibular ends of the muscles. Maxillary alveolar arches were used to
      restrain the skulls. Eight strain gauges were bonded to the surface of the
      midface to measure the strain under single muscle loading conditions (100 N).
      Maxillary strain gauges revealed a biaxial load state for both muscles. Thin
      antral bone experienced high maximum principal tensile strains (maximum of 685.5
      MUepsilon) and high minimum principal compressive strains (maximum of -722.44
      MUepsilon). Similar biaxial patterns of lower magnitude were measured on the
      zygoma (maximum of 208.59 MUepsilon for maximum principal strains and -78.11
      MUepsilon for minimum principal strains). Results, consistent for all specimens
      and counter to previously accepted concepts of biomechanical behavior of the
      midface under masticatory muscle loading, included high strain in the thin
      maxillary antral wall, rotational bending through the maxilla and zygoma, and a
      previously underestimated contribution of the temporalis muscle. This
      experimental model produced repeatable strain patterns quantifying the mechanics
      of the facial skeleton. These new counterintuitive findings underscore the need
      for accurate characterization of craniofacial strain patterns to address problems
      in the current treatment methods and develop robust design criteria.

PMID- 22976652
TI  - Difference in water accumulation patterns between solid and closed hollow
      obturators under a thermal cycle.
AB  - Water accumulation in the hollow space of a maxillary obturator is a continuing
      problem, and it is unclear whether the porosity of acrylic resin is involved in
      the mechanism. The purposes of the study were to evaluate the effect of a hollow
      space in the resin obturator on water sorption under a thermal cycle and to
      determine factors associated with water accumulation in the obturator. Twenty
      solid spheres (30-mm diameter) and 40 hemispheres (30-mm diameter, 1.5 mm
      thickness) were fabricated from heat-polymerized acrylic resin. Closed hollow
      specimens consisted of 2 hemispheres joined with autopolymerizing resin. Ten
      solid and 10 closed hollow specimens were immersed in distilled water, whereas
      the other specimens were stored at 100% relative humidity. Each specimen was
      thermocycled (5 degrees C-37 degrees C) with a dwell time of 12 hours and weighed
      every 12 hours for 180 days. Of the 20 closed hollow specimens, 16 showed no
      water accumulation (8 in distilled water, 8 at 100% humidity). The weight of
      these specimens became saturated by day 90, with increases from the initial
      weight of 1.41% at 5 degrees C and 1.36% at 37 degrees C. By day 180, the weights
      of the solid specimens had increased by 0.96% at 5 degrees C and 0.94% at 37
      degrees C. Weight fluctuation associated with temperature was observed for both
      types of specimens and for all storage conditions. It is concluded that water
      accumulation inside a closed hollow obturator is not directly related to the
      water absorption properties of the acrylic resin but is related to thermal damage
      of the obturator.

PMID- 22976653
TI  - Surgical repositioning of osseointegrated malposed dental implant with segmental
      osteotomy.
AB  - After extensive research, the practice with dental implants has been used on a
      large scale. With the increase in its indications in various local conditions,
      more complications have been observed. Among these, one of the most frequent is
      the installation of the implants in a three-dimensional altered position, making
      the prosthesis and aesthetics more difficult to achieve. For this reason,
      techniques such as segmental osteotomy have been developed and adapted to
      implantology to reestablish the adequate position of these implants with correct
      aesthetic outcome and function. The present clinical report shows the segmental
      osteotomy technique in a malposed osseointegrated dental position of the upper
      central incisor with 1-year follow-up.

PMID- 22976654
TI  - Facial resurfacing with a monoblock full-thickness skin graft after multiple
      malignant melanomas excision in xeroderma pigmentosum.
AB  - Xeroderma pigmentosum is an autosomal recessive disease, characterized by
      vulnerability of the skin to solar radiation. Increase in sunlight-induced cancer
      is a direct consequence of an increase in mutated cells of the skin of patients
      with xeroderma pigmentosum. There is no specific technique for facial resurfacing
      in patients with xeroderma pigmentosum. In this article, a patient with xeroderma
      pigmentosum with multiple malignant melanomas on her face and radical excision of
      total facial skin followed by facial resurfacing with monoblock full-thickness
      skin graft from the abdomen is presented.

PMID- 22976655
TI  - Dentoskeletal effects of 2-phase treatment versus 1-phase treatment with
      extraction of 4 first premolars in nonhypodivergent class II patients.
AB  - BACKGROUND: The aim of this study was to compare the effectiveness of 2-phase (a
      first phase with Twin Block therapy immediately followed by a second phase with
      fixed appliance therapy with nonextraction) and 1-phase (fixed appliance therapy
      with extraction of 4 first premolars) treatment of class II division 1
      malocclusion. METHODS: Two groups of successfully treated subjects, aged 10 to 14
      years with class II division 1 malocclusion, were evaluated: 2-phase group (n =
      70) and 1-phase group (n = 76). Pretreatment and posttreatment lateral
      cephalograms were traced manually and subjected to Student t test. RESULTS: In
      the 2-phase group, the forward positioning of the mandible (Pg-Olp) was less than
      that of the extraction group. The sagittal mandibular forward growth (Pg-Olp)
      was, on average, 2.39 +/- 0.4 mm in the 2-phase group and 4.56 +/- 2.51 mm in the
      1-phase group (P = 0.008, P < 0.05). In the vertical plane, the increases in
      lower facial height and mandibular plane angle were greater in the 2-phase
      treatment. In the 2-phase group, the lower anterior teeth proclined (Ii-MP) by
      7.3 +/- 2 degrees, and in the extraction treatment group, it changed -4.1 +/- 3.6
      degrees. The 1-phase group contributed more sagittal orthopedic effects than did
      the 2-phase group. CONCLUSIONS: The proclination of the mandibular incisors in
      the 2-phase group might restrain the mandibular bone from growing enough and
      cause the backward and downward rotation of the mandible.

PMID- 22976656
TI  - Endoscopic removal of throat-packing gauze swallowed during general anesthesia.
AB  - Throat packing is commonly placed in the pharynx before starting oral and
      maxillofacial surgery under general anesthesia to protect the airway from
      aspiration of blood and surgical debris. Complications such as airway obstruction
      may arise if any of the throat packing is retained after extubation, and less
      commonly, swallowing of the throat packing has been reported. We report
      endoscopic removal of throat packing gauze swallowed during general anesthesia.

PMID- 22976657
TI  - Interfaces of titanium implants and a vascularized osteocutaneous scapular graft
      revised with distraction osteogenesis.
AB  - This report assessed the bone-implant contact (BIC) and interthread bone density
      (BD) of 3 titanium implant interfaces retrieved from a mandible that was
      reconstructed with a vascularized osteocutaneous scapular graft and revised with
      multidirectional distraction osteogenesis before implant placement. The BICs and
      BDs were 86.9% and 92.8%, 67.3% and 80.6%, and 61.3% and 77.1%, respectively, for
      each of the implants in the graft that were revised 0 times, 1 time, and 2 times
      with distractions, respectively. The average rates of the BIC and BD of these 3
      implants were 73.9% and 84.7%, respectively. The present assessment indicates
      that there was sufficient osseointegration of the implants in the vascularized
      scapular bone graft even after revision with distraction osteogenesis.

PMID- 22976658
TI  - Correction of postsurgical alveolar ridge defect with vertical alveolar
      distraction of the onlay block graft.
AB  - Alveolar bone augmentation for dental implant rehabilitation is one of the
      greatest challenges for oral and maxillofacial surgeons. Bringing out an
      inadequate quantity of vertical bone during augmentation compromises correct
      implant positioning and the resulting prosthetic restoration. Alveolar
      distraction osteogenesis is now generally used in correcting alveolar ridge
      atrophy due to trauma, congenital defects, or periodontal defects. Onlay block
      grafting is a suitable method for restoring the alveolar bony defects. However,
      it sometimes can become a complicated procedure to repair the horizontal defect
      accompanying a vertical defect using only bone blocks. This clinical report
      presents a successful reconstruction of a severe anterior mandibular alveolar
      bony defect as a result of impacted teeth extraction and periodontal problem in a
      50-year-old healthy female patient. The defect was reconstructed with symphysis
      graft and platelet-rich fibrin in the first step. Vertical alveolar distraction
      was performed on the grafted site to maintain the suitable bony height 3 months
      later. Grafted bony segment distraction and the treatment options in similar
      cases were also discussed in this clinical report among with the literature.

PMID- 22976659
TI  - Effects of ultrasonic scaler tips and toothbrush on titanium disc surfaces
      evaluated with confocal microscopy.
AB  - PURPOSE: Instrumentation to remove plaque from dental implants may cause damage
      to the implant surface, and previous studies that have evaluated the effects of
      the ultrasonic scalers and brushing in experimental settings reported that
      substantial changes were seen on implant surfaces after mechanical plaque
      removal. There is limited information on changes of the surface profile and
      roughness of sandblasted acid-etched (SLA) and machined titanium surfaces after
      treatment with different instruments in simulated clinical situations. The
      purpose of this study was to evaluate the effects of oral hygiene instruments
      including various types of ultrasonic tips in simulated clinical settings and
      brushing with dentifrice on machined and SLA titanium surface with confocal
      microscopy. METHODS: Both SLA and machined discs were treated with various
      ultrasonic scaler tips and brushing. Discs were either instrumented with 4
      different ultrasonic scaler tips or brushed with dentifrice. The entire top
      surface of the discs was instrumented for a total of 40 seconds (20 seconds, 2
      cycles). Brushing with dentifrice was done for 40 seconds. Roughness measurements
      were performed using a confocal microscope. RESULTS: The change of surface
      structure after different treatment modalities could be observed with the naked
      eye when compared with the untreated surface (SLA and machined groups). In case
      of SLA surfaces, the 2 metal tips produced greater changes on the titanium
      surfaces when compared with the plastic ultrasonic tips and brushing. On the
      machined discs, scratch lines over the original surfaces could be observed from
      all ultrasonic metal and plastic tips, but 2 metal tips produced significant and
      definite scratches on the original disc surfaces. CONCLUSIONS: This study showed
      the effects of different types of ultrasonic tips and brushing with dentifrice on
      both SLA and machined titanium surfaces in simulated clinical setting. Within the
      limits of our study, we suggest that metal or plastic ultrasonic scaler tips may
      be applied as usual to treat the SLA surface of dental abutment or fixture
      surfaces without increasing the irregularities on the titanium surfaces. However,
      in case of machined surfaces, ultrasonic metal tips cannot be recommended because
      the surface becomes rougher after treatment. In addition, brushing of titanium,
      regardless of surface treatment (SLA and machined surfaces), resulted in
      reduction of surface roughness. Meticulous oral hygiene with brushing must be
      reinforced for the patients with dental implants to maintain the exposed implant
      surface clean. Brushing with dentifrice may facilitate maintaining the exposed
      fixture surface clean by smoothening the surface.

PMID- 22976660
TI  - Engineered autologous bone marrow mesenchymal stem cells:  alternative to cleft
      alveolar bone graft surgery.
AB  - Human recombinant bone morphogenetic protein 2 (rhBMP-2) accelerates bone
      regeneration but is associated with limited cementum and periodontal ligament
      regeneration, local root resorption, and ankylosis. This study assessed a new
      approach to the regeneration of the alveolar bone and periodontal attachment
      apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem
      cells (MSCs) engineered by replication defective adenovirus to express the BMP-2
      gene and pluronic F127 (PF127) in a large mammalian animal model. Bilateral
      maxillary periodontal defects were created over the premolar area in 9 mature
      male miniature swine. The 18 defects were randomly assigned to receive either BMP
      2-expressing MSCs in the advBMP-2 group or MSCs alone in the MSC group. The
      regenerated periodontal attachment apparatus was evaluated histologically, and
      the total regenerated bone volume was calculated from three-dimensional computed
      tomography analysis. Three months after implantation, significant bone volume was
      regenerated in the advBMP-2 group. Periodontal apparatus regeneration was
      significantly better in the advBMP-2 group. New cementum and Sharpey fibers were
      observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete
      healing with localized root surface resorption was noted in the control group.
      The use of ex vivo BMP-2-engineered autologous MSCs enhanced bone and periodontal
      apparatus regeneration in maxillary alveolar and periodontal defects in swine.
      This novel integrated approach might be suitable for clinical periodontal
      apparatus repair. This may be an alternative for cleft alveolar bone graft
      surgery.

PMID- 22976661
TI  - Plexiform hypoglossal schwannoma of the tongue and the submandibular region.
AB  - Hypoglossal schwannomas usually develop in the intracranial portion of the brain.
      Incidence of hypoglossal schwannomas of the submandibular region is extremely
      rare. A 27-year-old patient presented to us with hypoglossal schwannoma of the
      tongue and the submandibular region. The tumor was excised intraorally combined
      with submandibular approach. Histopathologic examination revealed a plexiform
      schwannoma (a rare variant).

PMID- 22976662
TI  - Huge internal carotid artery aneurysm presenting as tonsillar asymmetry.
AB  - Aneurysms of the extracranial portion of the carotid artery are extremely rare.
      Internal carotid artery aneurysm is an uncommon cause of tonsillary asymmetry.
      Although internal carotid artery aneurysms usually remain asymptomatic, the
      clinical manifestation requires the tonsillar enlargement. Asymmetry as a sole
      determining factor for tonsillectomy may lead to unnecessary operations. We
      report a patient with a giant internal carotid artery aneurysm presenting as
      tonsillary asymmetry that might be mistaken for a tonsillar neoplasia. When faced
      with a tonsillar asymmetry, an otolaryngologist must keep aneurysms in mind.

PMID- 22976663
TI  - Computer-assisted navigational surgery improves outcomes in orbital
      reconstructive surgery.
AB  - Orbital reconstruction is a difficult procedure, success of which is dependent on
      the surgeon's experience. The lack of objective methods requires a fair amount of
      estimation is its execution. This study evaluates the efficacy of Kolibri
      (BrainLab, Munich, Germany), an intraoperative navigation device, in improving
      outcomes. From 2004 to 2009, 58 patients with orbital trauma who underwent
      surgery at the National University Hospital, Singapore, were included in this
      prospective matched control trial. Twenty-nine consecutive patients underwent
      surgery with Kolibri. The control group underwent surgery without the device.
      Both groups were matched for age, sex, orbital wall fracture, preoperative
      ophthalmologic features, etiology and severity of trauma, surgical approach, and
      types of implant used. The postoperative follow-up was at 1, 3, 6, and 12 months.
      For subjective assessment, the postoperative ophthalmologic features, including
      diplopia, infraorbital hypoesthesia, ophthalmoplegia, and enophthalmos, were
      compared. At 1, 3, 6, and 12 months, respectively, there were fewer patients with
      postoperative ophthalmologic complications in the study group (italicized; n =
      29) compared with the control group (n = 29; P < 0.05): 12/29 (41%) versus 21/29
      (72%), 8/29 (28%) versus 19/29 (66%), 5/29 (17%) versus 15/29 (52%), and 2/29
      (7%) versus 12/29 (41%). For objective assessment, using the Kolibri workstation,
      operative plans were created and fused with postoperative computed tomographic
      scans. Vertical distances between the actual reconstructed and planned orbital
      floors were measured. On average, the vertical distance measured from the
      boundaries of floor defects for patients in the study group was 3.24 mm (95%
      confidence interval, 1.56-4.91) lower than the control group (P = 0.001). In
      conclusion, navigation minimizes postoperative complications, reduces the need
      for repeat procedures, and helps surgeons with planning, execution, and
      postoperative assessment.

PMID- 22976664
TI  - In vitro biomechanical evaluation of modified plating techniques for bilateral
      sagittal split ramus osteotomy in mandibular advancement.
AB  - The aim of this study was to compare the biomechanical properties of modified
      plate techniques using a newly designed three-dimensional test model after
      sagittal split ramus osteotomy. Fifteen synthetic polyurethane mandibular
      replicas were used and divided into 3 groups. Self-tapping 6-mm titanium screws
      with an outer diameter of 2.0 mm and private designed plates produced by 316-L
      stainless steel were used in the study. After the osteotomy, the distal part was
      advanced by 5 mm. The jaw models were placed to the three-dimensional test model
      designed by the authors, and the Instron Lloyd LRX device was used to apply a
      double-sided tensile force from the mandible angulus region of each group.
      Resistance forces that caused a displacement of 1.5 and 3 mm were recorded with
      the Instron program. The mean (SD) of the 3 groups were calculated using analysis
      of variance and the Tukey test. The results were compared statistically, with
      values of P < 0.05 determined as statistically significant. On the basis of the
      results of the Tukey comparison within the groups, there was a statistically
      significant difference between groups 1 and 2 and between groups 1 and 3 at both
      1.5- and 3-mm displacement (P < 0.05). No significant difference was observed
      between groups 2 and 3 (P > 0.05). This test model was able to identify the most
      appropriate plate type of 3 different modified plate techniques after sagittal
      split ramus osteotomy.

PMID- 22976665
TI  - Surgical removal of impacted maxillary canines.

PMID- 22976666
TI  - Self-locking sliding knot to manage upper third molar extraction.

PMID- 22976667
TI  - Preserving capsule formation after removal of dura mater complex increases risk
      of cranial infection relapse.

PMID- 22976668
TI  - Use of platelet-rich plasma in maxillofacial surgery.

PMID- 22976669
TI  - Bloodless cleft surgery using vascular clamp.

PMID- 22976670
TI  - Efficacy of external and endonasal dacryocystorhinostomy.

PMID- 22976671
TI  - Management of a needle breakage during third molar extraction with C-ARM digital
      fluoroscope.

PMID- 22976672
TI  - Quantitative survey of human leg toes shape.
AB  - The present article is a follow-up to previous articles published in this journal
      entitled "Numerical Survey of the Different Shapes of Human Nose" and "Ear Concha
      Shapes." Here we report experimental results for the numerical quantities of the
      different shapes of human leg toes shapes. To the best of the author knowledge,
      this approach has never been applied.

PMID- 22976673
TI  - Warthin tumor arising from the minor salivary gland.
AB  - Warthin tumor (WT) accounts for 4% to 13% of all salivary gland tumors. This
      benign tumor, which commonly arises in the parotid gland, is the second most
      common tumor of the salivary gland. WT is multicentric in 12% to 20% of patients
      and is bilateral in 5% to 14%. The mean age at diagnosis is 62 years (range, 12
      92 years), and it rarely presents (<6%) before age 40 years. Extraparotid WT,
      arising from the submandibular gland or cervical lymph node for example, is very
      infrequent, with corresponding incidences of 0.4% to 6.9% and 8%, respectively.
      Moreover, WT arising from the minor salivary gland is extremely rare, with a
      reported incidence of merely 0.1% to 1.2%. We report here WT arising from the
      minor salivary gland in the buccal mucosa in a 66-year-old woman and review cases
      of WT of the minor salivary gland reported in the English literature.

PMID- 22976674
TI  - Conservative treatment of unilateral displaced condylar fractures in children
      with mixed dentition.
AB  - PURPOSE: The aim of the study was to present the outcomes of the conservative
      treatment of unilateral displaced condylar fractures in a series of children with
      mixed dentition. METHODS: The treatment protocol of our study population included
      the placement of fixed orthodontic appliances, the preparation of a maxillary
      acrylic splint, and functional exercises. Six and 12 months after trauma,
      patients underwent clinical temporomandibular joint dysfunction and mandibular
      motion assessments and a panoramic radiography. RESULTS: Fourteen children with a
      mean age of 7.2 years were included in the study. At 1 year follow-up, complete
      clinical and functional recovery was observed in all patients. A complete healing
      process leading to a normal condylar process was observed in almost all patients.
      CONCLUSIONS: Conservative treatment of displaced condylar fractures in children,
      using a progressively remodeled splint, showed satisfactory functional outcomes
      at 12 months of follow-up.

PMID- 22976675
TI  - Use of Integra and interval brachytherapy in a 2-stage auricular reconstruction
      after excision of a recurrent keloid.
AB  - Keloids present a formidable clinical challenge. Surgical excision in conjunction
      with radiation therapy may decrease the chance of keloid recurrence. Split
      thickness skin grafts, however, are more prone to failure in the setting of
      radiation. In this report, we present a patient with a recurrent auricular keloid
      who underwent excision and immediate Integra (Integra LifeSciences, Plainsboro,
      NJ) application, followed by high-dose rate brachytherapy and interval split
      thickness skin graft placement. A 23-year-old woman with a history of a recurrent
      auricular keloid after previous surgical excision, corticosteroid injection, and
      radiation underwent reexcision of her keloid. Integra was used to cover the
      resultant exposed auricular perichondrium. The patient then received high-dose
      rate brachytherapy (1500 cGy) on postoperative days 1 and 2, followed by
      definitive split-thickness skin graft placement 3 weeks after her initial
      surgery. The patient recovered from all interventions without complication. There
      was no evidence of keloid formation 27 months after the interval split-thickness
      skin graft placement at either the auricular recipient or thigh donor sites. We
      report the first case of a 2-stage reconstruction of a recurrent auricular keloid
      (composed of keloid excision and placement of Integra in conjunction with high
      dose rate brachytherapy, followed by interval split-thickness skin grafting),
      resulting in an acceptable cosmetic result without evidence of recurrence at long
      term follow-up.

PMID- 22976676
TI  - Use of immediate dermal fat graft for scalp contour defect following resection of
      arteriovenous malformation.
AB  - Arterial venous malformations (AVMs) are rare conditions that are difficult to
      manage. Therapeutic options include selective embolization with or without
      surgical excision. Recurrence, however, is high despite correction of the primary
      abnormality. Cosmetic concern is among the indications for treatment,
      particularly if the AVM occurs on the face or scalp. Historically, AVM excision
      and the residual defect correction have been performed separately. We present the
      first case reported of a successful embolization and interval excision with
      immediate reconstruction using a dermal fat graft, as a novel approach to correct
      soft tissue defect following the resection of an AVM. A 35-year-old man presented
      with a 20-year history of a nonpulsating mass posterior to the hairline in the
      right frontoparietal region, measuring 4.0 cm on its longest axis. Embolization
      of the AVM was achieved by injecting N-butyl cyanoacrylic acid and ethiodol. One
      month after embolization, surgical excision of the mass was performed. The
      resulting disfiguring contour defect was immediately corrected using a dermal fat
      graft harvested from the groin. At 4 months' follow-up, the graft was viable with
      no evidence of resorption or epidermal cyst formation. In addition, there was no
      recurrence of the AVM and no complications at the donor site. This case
      demonstrates the utility of a dermal fat grafts in correcting the impending
      defect in 1 stage avoiding a second-stage procedure and significant period of
      cosmetic disfigurement. This method should be considered as a treatment option
      for patients requiring moderately sized AVM excisions in cosmetically sensitive
      areas.

PMID- 22976677
TI  - Implant-assisted dental rehabilitation of a patient with maxillary
      rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is a malignant, soft tissue neoplasm consisting of cells derived
      from the primitive mesenchyme that exhibit a profound tendency to undergo
      myogenesis. Multimodality therapy for tumors in the head and neck regions has a
      significant effect on maxillofacial skeletal growth, dental development, and the
      whole ecologic system of the oral cavity. Here we aimed to discuss the influence
      of head-neck cancer therapy in pediatric patients with long-term follow-up and
      present a case with implant-assisted dental rehabilitation and also functional
      and aesthetic outcomes.

PMID- 22976678
TI  - Treatment of postburn anteriorly located neck contractures with local flaps.
AB  - OBJECTIVE: The objective of this study was to summarize our experience of using
      local flaps for the reconstruction of neck defects after cervical contractures
      release, particularly of using the extended deltopectoral flaps whose distal
      margin was beyond the anterior axillary line even reaching dorsalis for
      reconstruction of anterior neck scar contractures in a single-stage procedure.
      METHODS: From 1987 to 2008, neck scar contractures were reconstructed using
      various local flaps in 68 patients with postburn anteriorly located neck
      contractures. The local flaps used consisted of 36 deltopectoral flaps, 6
      extended deltopectoral flaps, 4 free scapular flaps, 8 neck-shoulder flaps, and
      14 Z-plasties. The distal end of extended deltopectoral flaps was transferred as
      microvascular-free flap provided by the posterior circumflex humeral artery, but
      the proximal end as pedicle flap supplied by the anterior perforating branches of
      internal mammary artery. Other flaps were elevated conventionally as described
      previously in the articles. RESULTS: Of 68 patients, there were 59 cases (86.8%)
      whose release of the contractures was excellent. For 51 patients, the whole
      process of treatment was finished only in a single-stage procedure. We used
      extended deltopectoral flap, which was developed from our own anatomic studies
      and from previous reports in the literature, in 6 patients. This new flap extends
      the volume of the original deltopectoral flap, from 22 to 32 cm in length and 10
      to 22 cm in width (at the apex). Postoperatively, all flaps survived completely.
      Patients were satisfied with their results. The follow-up period ranged 1 to 10
      years; no obvious recontractures have been noted. There were no severe donor-site
      complications. CONCLUSIONS: The local flap with matching texture, color,
      elasticity, and pliability is still the best choice for reconstruction of
      postburn anteriorly located neck contractures. The extended deltopectoral flap
      has been used successfully to yield satisfactory outcomes for the scar
      contractures in the anterior neck and should be conserved as a selective method
      for reconstructive surgeons.

PMID- 22976679
TI  - Giant ethmoido-orbital osteoma presenting with dacryocystitis and metamorphopsia.
AB  - Osteoma is the most common benign neoplasm of the paranasal sinuses. Intraorbital
      extension is rare. Here we report a 16-year-old adolescent boy who presented with
      epiphora and pain in the medial canthal area. A computed tomographic scan
      revealed a bone density mass in the left ethmoid cavity extending into the
      adjacent orbit. The tumor was removed via endoscopic endonasal surgery. The
      pathologic evaluation was consistent with osteoma. After surgery, all complaints
      have been resolved and there was not any sign of recurrence in the computed
      tomographic scan.

PMID- 22976680
TI  - Dermoid cyst:  unusual localization.
AB  - Dermoid cysts are embryonic lesions usually observed in the lateral eyebrow
      region and the midline nose and neck areas. Communication of these lesions with
      the central nervous system is rare and occurs in the nasal region. There are few
      clinical reports of temporal dermoid cysts presenting with intracranial
      extension, and we present a 15-year-old girl with a fronto-orbital dermoid cyst
      with intracranial extension and bone erosion. Her presenting symptom was a
      lacrimation reduction of the left eye. Excision of the cyst was done using a
      coronal approach because of its extension and localization.

PMID- 22976681
TI  - Accident entry of titanium screw into the sphenoid sinus during paranasal
      augmentation with porous polyethylene implant.
AB  - We report a rare case of accident entry of titanium screw into the sphenoid sinus
      during paranasal augmentation with porous polyethylene implant. The screw was
      finally retrieved from the sphenoid sinus by a nasal endoscope. We emphasize
      that, on this surgery region, the simple fixation skill must be performed
      delicately. Otherwise, an adverse event may still happen.

PMID- 22976682
TI  - Canalicular adenoma of the palate.
AB  - Canalicular adenomas are uncommon, benign epithelial neoplasm of the salivary
      glands that usually involve the upper lip and the buccal mucosa of elderly
      people. Differential diagnosis of the canalicular adenoma versus adenocarcinoma
      is important because it may result in unjustified radiotherapy or extensive and
      aggressive surgery. Despite the benign nature of canalicular adenomas, complete
      surgical removal and a regular clinical follow-up are recommended. The current
      study describes the diagnostic procedures, surgical management, and follow-up of
      a canalicular adenoma involving the palate of a 79-year-old man.

PMID- 22976683
TI  - Using the condylar prosthesis after resection of a large odontogenic myxoma tumor
      in the mandible.
AB  - Odontogenic myxomas are considered to be a benign odontogenic tumor with locally
      aggressive behavior. Because these neoplasms are rare in the oral cavity, the
      possible surgical management can be quite variable. Literature recommendation can
      vary from simple curettage and peripheral ostectomy to segmental resection. The
      authors report a case of a 20-year-old patient with an odontogenic myxoma tumor
      located in the left mandibular angle, ascending ramus, and mandibular symphysis.
      It was treated by radical resection followed by titanium reconstruction with
      condylar prosthesis, which allowed rapid return of function with improvement in
      quality of life and restoration of cosmetic and functional deficits. The lesion
      did not recur after surgical procedure.

PMID- 22976684
TI  - Mini-retromandibular access to the condyle in panfacial fractures.
AB  - Surgical management of panfacial fractures can be extremely challenging. The many
      fracture lines and lack of landmarks make it difficult to restore the facial
      skeletal morphology. Extracapsular fractures of the mandibular condyle require
      open reduction and internal fixation to restore the vertical and sagittal
      dimensions of the mandible, representing the base for further facial skeleton
      reconstruction. Six patients with panfacial fractures, including a bilateral
      extracapsular condylar fracture, were treated between January 2006 and November
      2009. One patient underwent surgical procedure 60 days after the injury. The
      condylar fractures were treated via a mini-retromandibular access. Overall, the
      bone morphology restoration was good. In particular, all of the condylar
      fractures were reduced satisfactorily. No complication was detected, and no
      facial nerve lesion was observed. The literature contains many proposals for
      surgically accessing panfacial fractures. Open reduction and internal fixation of
      condylar fractures are crucial for restoring face height. The mini
      retromandibular access is especially suitable, because it allows safe, rapid
      surgical management.

PMID- 22976685
TI  - Importance of clinical examination in dentoalveolar trauma.
AB  - Dental injuries are often the result of direct trauma. The most affected teeth
      are the upper incisors, and the most frequent lesions are coronal fractures,
      contusions, and lip and alveolar mucosa lacerations. The objective of this study
      was to draw attention to the importance of the correct management of cases of
      crow fractures associated with soft tissue lacerations when the fragment is not
      located. This is a clinical case of crown fracture, the fragment of which
      remained lodged inside the lip. After fragment removal, the clinical case showed
      a satisfactory repair emphasizing the importance of a meticulous clinical
      examination to achieve a correct diagnosis and an appropriate treatment plan,
      which is essential for a favorable prognosis.

PMID- 22976686
TI  - Total autogenous mandibular reconstruction using virtual surgical planning.
AB  - Free fibula transfer has become the workhorse in mandibular reconstruction. Total
      mandibular reconstruction is an uncommon procedure with added complexity.
      Numerous techniques have been described for such reconstruction, many requiring a
      temporomandibular joint prosthesis. We present a novel method where simultaneous
      bilateral free fibula transfer utilizing preoperative virtual surgical planning
      was used to produce a total autogenous reconstruction. The virtual surgical
      planning allows to effectively quantify the bone stock required preoperatively
      and facilitates intraoperative modeling of the fibula. Therefore, a more
      anatomically correct reconstruction is obtained resulting in improved functional
      and aesthetic outcomes.

PMID- 22976687
TI  - Orthognathic surgery of a patient with oligodontia:  alternative technique for
      intermaxillary fixation.
AB  - Oligodontia may cause various problems during orthognathic surgery because it may
      be difficult to fix the surgical guide splints. The aim of this clinical report
      was to present an alternative technique for intermaxillary fixation of a patient
      with oligodontia and facial deformity. A 20-year-old male patient, whose 8
      maxillary and 11 mandibular teeth were congenitally missing, was treated using
      bimaxillary orthognathic surgery. Before the surgical approach, fixed mandibular
      prosthesis containing pins on the vestibule sides of the crowns was constructed
      to provide anchorage for intermaxillary splint and to achieve occlusal stability
      and vertical dimension during the surgery. This prosthesis was also used to hang
      intraoral elastics during the postoperative orthodontic treatment. At the end of
      treatment, these pins were cut, composite restoration material was applied to
      camouflage the places of the pins, and the patient continued to use this
      prosthesis. The patient gained an appropriate facial aesthetics and oral function
      using multidisciplinary approach.

PMID- 22976688
TI  - Reconstruction of a near-total nasal defect using a precontoured titanium mesh
      with a converse scalping flap.
AB  - The reconstruction in case of large nasal defects, especially affecting the
      cartilaginous portion, is a surgical and aesthetic challenge. The result has to
      fulfill functional and aesthetic aspects concerning shape, texture, and nasal
      breathing, which requires accurate reproduction of nasal lining, support, and
      coverage. Here, we describe nasal reconstruction in a 36-year-old woman after
      near-total nasal resection due to a malignant peripheral nerve sheath tumor in
      the glabellar and nasal regions. After tumor resection, the cartilaginous and
      bone structures were reconstructed using a dynamic titanium mesh, which was
      precontoured on a three-dimensional-print model of the preoperative situation.
      Soft tissue defects were covered as a 2-stage procedure using a Converse scalp
      flap. We achieved an adequate long-term functional and aesthetic and oncological
      result. Titanium mesh in combination with Converse flap proved to be an
      alternative in extensive composite midfacial defects.

PMID- 22976689
TI  - Adult rhabdomyoma with oncocytic changes affecting the floor of the mouth: 
      optical, immunohistochemical, and ultrastructural study.
AB  - Adult rhabdomyoma (AR) is an extremely uncommon benign neoplasm with mature
      skeletal muscle differentiation comprising approximately 2% of muscle tumors,
      usually affecting the soft tissue of the head and neck. Although histology of AR
      is characteristic, several differential diagnoses (granular cell tumor,
      hibernoma, oncocytoma) should be considered, and one needs to be familiar with
      this rare entity to exclude other neoplastic diseases. We present a case of AR,
      in a 54-year-old man, affecting the floor of the mouth, and call attention to the
      oncocytic appearance (including antimitochondrial and peroxiredoxin I
      immunoreactivity) of this case and its differential diagnosis analyzed at the
      optical, immunohistochemical, and ultrastructural level, showing the
      morphological and immunohistochemical features that can be confused with a
      salivary oncocytoma.

PMID- 22976691
TI  - External fixation in a low-velocity gunshot wound to the mandible.
AB  - Low-velocity gunshot wounds to the mandible are complex injuries that can be
      aesthetically and functionally devastating. Despite advances in plating systems
      and surgical techniques, repair of such injuries remains a challenging endeavor.
      Traditionally, external fixation has resulted in longer treatment times and the
      need for revision surgery. Rigid fixation has many proponents because of shorter
      postoperative treatment times and fewer complications. We report a case of a low
      velocity gunshot injury to the mandible with comminution and a full-thickness
      soft tissue wound treated definitively with maxillomandibular fixation and an
      external fixation device.

PMID- 22976690
TI  - Mandibular angle fracture treated with new three-dimensional grid miniplate.
AB  - Fractures of the mandibular angle deserve particular attention because they
      represent the highest percentage of mandibular fractures and have the highest
      postsurgical complication rate, making them the most challenging and
      unpredictable mandibular fractures to treat. Despite the evolution in the
      treatment of maxillofacial trauma and fixation methods, no single treatment
      modality has been revealed to be ideal for mandibular angle fractures. Several
      methods of internal fixation have been studied with great variation in
      complications rates, especially postoperative infections. Recently, new studies
      have shown reduction of postsurgical complications rates using three-dimensional
      plates to treat mandibular angle fractures. Nevertheless, only few surgeons have
      used this type of plate for the treatment of mandibular angle fractures. The aim
      of this clinical report was to describe a case of a patient with a mandibular
      angle fracture treated by an intraoral approach and a three-dimensional
      rectangular grid miniplate with 4 holes, which was stabilized with monocortical
      screws. The authors show a follow-up of 8 months, without infection and with
      occlusal stability.

PMID- 22976692
TI  - Role of orthognathic surgery in the treatment of recurrent mandibular
      dislocation:  importance of mandibular ramus inclination.
AB  - The management of chronic mandibular dislocation is controversial: many advocate
      conservative treatment, whereas others believe surgery can improve the symptoms
      and prevent dislocation recurrence. We report 7 consecutive cases of
      hyperdivergent patients with recurrent mandibular dislocation, who were treated
      using combined maxillary surgery that allowed the modification of the facial
      pattern from dolichofacial to mesofacial. At a 1-year follow-up, all patients did
      not have any episode of mandibular dislocation; moreover, a general improvement
      of symptoms associated with temporomandibular joint disorders was observed.

PMID- 22976693
TI  - Survey on complications of orthognathic surgery among oral and maxillofacial
      surgeons.
AB  - BACKGROUND: Orthognathic surgery is performed to correct dentofacial and
      craniofacial deformities and improve facial aesthetics, occlusal relations, and
      the functionality of the stomatognathic apparatus. However, complications in
      orthognathic surgery may occur at any time during the course of treatment: in the
      preoperative judgment and planning, during perioperative orthodontic care, or
      intraoperatively. The aim of the current study was to survey oral and
      maxillofacial surgeons regarding the main complications of orthognathic surgery.
      METHODS: One hundred oral and maxillofacial surgeons with at least 5 years of
      experience in dentofacial management were interviewed during a Brazilian national
      oral and maxillofacial surgery meeting by 2 calibrated postgraduate students,
      using a questionnaire addressing complications of orthognathic surgery. RESULTS:
      No significant differences were found regarding educational background or
      postgraduate degrees among the oral and maxillofacial surgeons (P > 0.05). A
      total of 28.0% had no experience with vertical osteotomy of the mandibular ramus,
      35.0% had no experience with subapical osteotomy of the mandible, and 4.0% had no
      experience with genioplasty. All participants had experience with sagittal
      osteotomy of the mandibular ramus. Among mandible procedures, the most common
      complication was nerve damage, followed by unfavorable osteotomy. The most common
      Le Fort I complication was also nerve damage (40%), followed by hemorrhage (29%).
      Regarding osteosynthesis fixation, fractures of the material were more frequent
      in the mandible (23%) and maxilla (10%). CONCLUSIONS: Most oral and maxillofacial
      surgeons experienced similar orthognathic surgery complications to those reported
      in retrospective studies.

PMID- 22976694
TI  - Osteoconductive properties of beta-tricalcium phosphate matrix, polylactic and
      polyglycolic acid gel, and calcium phosphate cement in bone defects.
AB  - Extensive bone defects in maxillofacial region can be corrected with autogenous
      grafts; otherwise, the disadvantages of the therapeutics modality take the
      research for new bone substitutes. The aim of the study was to evaluate and
      compare the osteoconductive properties of 3 commercial available biomaterials. A
      total of 30 calvarial defects (5-mm diameter) were randomly divided into 5
      treatment groups, with a total of 6 defects per treatment group (n = 6). The
      treatment groups were as follows: 500 to 1000 MUm beta-tricalcium phosphate (beta
      TCP), polylactic and polyglycolic acid (PL/PG) gel, calcium phosphate cement,
      untreated control, and autograft control. The evaluations were based on
      histomorphometric analysis at 60 postoperative days. The results have shown that
      beta-TCP and autograft control supported bone formation at 60 postoperative days.
      beta-Tricalcium phosphate showed the highest amount of mineralized area per total
      area and statistically significant compared with PL/PG, calcium phosphate cement,
      and untreated control groups. The PL/PG gel does not have osteoconductive
      properties and performed similar to empty control. Calcium phosphate cement
      showed higher number of multinucleated giant cells around the sites of the
      biomaterial and showed newly formed bone only at the edges of the biomaterial,
      without bone formation within the biomaterial. The findings presented herein
      indicate that bone formation reached a maximum level when rat calvarial defects
      were filled with beta-TCP at 60 postoperative days. Further studies should be
      conducted with beta-TCP to understand the potential of this biomaterial in bone
      regeneration.

PMID- 22976695
TI  - Paranasal sinus osteomas.
AB  - Osteoma is the most common benign tumor of the paranasal sinuses. They remain
      asymptomatic until the tumor reaches a certain size. Although the etiology of the
      osteomas is controversial, embryologic, traumatic, and infective theories have
      been proposed. Osteomas may be discovered at any age but are usually found during
      the fourth and fifth decades, and there is a male preponderance. In this
      retrospective study, we analyzed 25 patients with paranasal sinus osteomas who
      were treated surgically between 2005 and 2011. Age and sex of the patient, size
      and location of the tumor, clinical presentation, type of surgical approach,
      duration of follow-up, outcome, and any intraoperative or postoperative
      complications were obtained from the medical records of the patients. Diagnosis
      of osteoma was based on computed tomography findings and confirmed
      histopathologically in all cases. There were 9 men (36%) and 16 women (64%) with
      a mean age of 38.7 years. Tumor localization was divided as follows: ethmoid
      sinus in 14 patients (56%), frontal sinus in 9 patients (36%), and maxillary
      sinus in 2 patients (8%). Mean tumor size was 2.04 cm, ranging from 0.5 to 6.5
      cm. External approach was used in 9 cases and endonasal endoscopic surgery was
      performed in 19 cases. Combination of endoscopic surgery and external surgery was
      performed in 3 cases. After at least 6 months of follow-up, all patients were
      symptom-free except 2 patients who underwent revision surgery. These 2 patients
      were also asymptomatic following revision surgery. Although there is an
      increasing trend to endoscopic surgery, external approach is recommended in large
      frontal osteomas and ethmoid osteomas with lateral extension and in case of
      intracranial or intraorbital involvement.

PMID- 22976696
TI  - Anterolateral thigh flap for reconstruction of periorbital defect.
AB  - A 49-year-old man presented with basal cell carcinoma for 12 years and 3
      surgeries. Here, we have used the pedicled anterolateral thigh flap to cover his
      periorbital defect. To our knowledge, pedicled anterolateral thigh flap can be
      used reliably and safely to cover defects in facial reconstruction.

PMID- 22976697
TI  - Endonasal endoscopic approach for recurrent nasolabial cyst.
AB  - Nasolabial cysts are rare nonodontogenic cystic lesions in the soft tissue of the
      midface and usually present with painless asymptomatic swelling in the nasolabial
      region. Surgical excision via sublabial approach is considered as the standard
      treatment. However, endonasal endoscopic marsupialization of the cyst is reported
      as an effective alternative method for nasolabial cysts. Marsupialization of the
      cyst is believed to integrate the nasolabial cyst into a part of the nasal cavity
      as an air-containing sinus. In this article, we present an endonasal endoscopic
      marsupialization technique in case of recurrent nasolabial cyst. To draw
      attention to this approach, we present our case with current literature.

PMID- 22976698
TI  - Reverse quad helix appliance:  differential anterior maxillary expansion of the
      cleft area before bone grafting.
AB  - Cleft-affected cases present a variable degree of transversal constriction of the
      maxilla. Our aim is to present a new method for differential expansion of the
      premaxillary area in unilateral cleft lip and palate-affected patients. The
      reverse quad helix appliance is made of a 0.036-in stainless-steel wire soldered
      to 2 bands placed on maxillary deciduous canines or first primary molars (or
      first permanent premolars). It incorporates 4 helical loops forming an inverse W
      arch design. The spring is positioned posterior to the banded teeth; thus, the
      expansion effect is focused in the anterior maxillary region. A reverse quad
      helix appliance was activated and cemented in 20 patients for premaxillary
      expansion. Upper arch width was assessed by means of plaster study models in the
      anterior and posterior maxillary regions. The mean anterior occlusal expansion
      achieved by the reverse quad helix (9.60 [+/-5.24] mm) is statistically
      significantly larger than that achieved in the posterior region (5.50 [+/-3.07]
      mm) (P < 0.0001). The reverse quad helix is an efficient appliance for
      differential expansion of the anterior maxillary region as a preparatory stage
      for secondary bone graft procedures in unilateral cleft lip and palate-affected
      patients.

PMID- 22976699
TI  - Cervical osteophytes:  a rare cause of obstructive sleep apnea.
AB  - Uncertain etiology of cervical osteophytes, in particular emerging in geriatric
      population, is a rare skeletal system disease. Often, the cases are asymptomatic
      and may lead to symptoms such as dysphagia, cough, dyspnea, and dysphonia. We
      present a patient who had anterior osteophytes causing symptoms of severe
      obstructive sleep apnea (OSA), and literature on etiology of OSA has been
      reviewed. A 57-year-old male patient with complaints of snoring and cessation of
      breathing during sleep was referred to the ear nose throat clinic. Cervical
      radiograph and computed tomography showed the osteophytes in the anterior of the
      vertebral corpus at the level C1-2. In addition, bridging osteophyte was observed
      between C6 and C7 vertebrae. The patient's neck circumference was 41 cm, body
      mass index was 29 kg/m2, Epworth Sleepiness Scale score was 11, and apnea
      hypopnea index was 62. Surgery was recommended, but the patient refused.
      Continuous positive airway pressure titration was applied with 12.6 cm H2O
      pressure; apnea control was attained with an AHI of 2.7. One of the rare causes
      of OSA, a case of cervical vertebral osteophyte, was presented, and we would like
      to draw attention to the importance of ear nose throat examination in the
      diagnosis of OSA.

PMID- 22976700
TI  - Immediate osseous genioplasty with Kirschner wire fixation for revision of
      infected alloplastic chin implant.
AB  - Genioplasty is a useful tool for correction of congenital abnormalities, as well
      as for aesthetic improvements of the lower face. Both alloplastic implantation
      and osseous genioplasty techniques have long been used successfully to achieve
      satisfactory outcomes. However, alloplastic implantation can be associated with
      several known complications, including infection, bone resorption, and secondary
      soft tissue deformities. Typically, these issues arise in the early postoperative
      period, but there have been reported instances of late infectious complications
      and the associated sequelae. These cases are generally treated with removal of
      the implant and secondary revision at a later date. We present here the unique
      case of a 65-year-old woman who presented with an infected silicone chin implant
      25 years after her initial surgery. In this case, we chose to perform an
      immediate osseous genioplasty at the time of implant removal to avoid the
      problems that can arise from unpredictable soft tissue healing, as well as an
      untoward aesthetic result from the significant bone resorption that had occurred
      in this patient. To minimize the presence of exposed hardware in this
      contaminated field, we used intraosseous Kirschner wire fixation for
      osteosynthesis of the advanced genial segment. Our patient experienced no
      complications from this procedure, the infection cleared, and a successful
      aesthetic outcome was achieved with this technique.

PMID- 22976701
TI  - Buccal branch as a guide for superficial parotidectomy.
AB  - Superficial parotidectomy is the preferred method for treating lesions of the
      parotid gland. Several methods of identification and dissection of the facial
      nerve have been reported, including antegrade and retrograde dissection. AIM: The
      aim of this study was to determine the role of the buccal branch of the facial
      nerve use as a guide in retrograde approach that minimizes injury to the facial
      nerve and maximizes the rate at which it recovers. RESULT: Fifteen patients who
      underwent superficial parotidectomy by retrograde approach between 2009 and 2011
      at the Maxillofacial Department, Medical City Hospital Baghdad, were included in
      this study. The study group included 6 males and 9 females, with ages ranging
      from 25 and 66 years. Temporary facial nerve weakness was noticed in 4 patients
      (26.6%); full recovery of the facial nerve function in those patients had been
      noticed between 3 and 8 weeks. Sialocele was noticed in 1 patient (6.6%).
      CONCLUSIONS: Retrograde approach guided by buccal branch is simple and less time
      consuming and has less risk for facial nerve injury.

PMID- 22976702
TI  - Recurrent pleomorphic adenoma of the parotid gland:  role of neutron radiation
      therapy.
AB  - Recurrent pleomorphic adenoma (RPA) of the parotid gland represents a challenging
      task for maxillofacial surgeons. The role of radiotherapy in the treatment of RPA
      of the parotid gland has been studied in previous experiences, and its use has
      been considered questionable. The aims of our article were to analyze and
      illustrate a case of RPA, initially treated with enucleations at another
      institution, showing a multinodular pattern with positivity for S-100 protein and
      cytokeratin, managed with conservative parotidectomy and neutron radiotherapy.

PMID- 22976703
TI  - Sclerosing polycystic adenosis of the parotid gland.
AB  - Sclerosing polycystic adenosis (SPA) is an uncommon salivary gland lesion similar
      to fibrocystic disease and adenosis of the mammary glands. To our knowledge, 51
      cases of SPA have been reported in the literature to date. Sclerosing polycystic
      adenosis is well circumscribed, yet not encapsulated, and has sclerotic and
      irregularly defined lobules composed of abundant hyalinized collagen with ductal,
      acinar hyperplasia and areas of apocrine metaplasia. Focal cystic spaces within a
      dense fibrotic stroma are also characteristic features of this lesion. Most of
      the known cases occurred mainly in the parotid gland. In this article, we
      describe a case of SPA occurring in the parotid gland of a 47-year-old male
      patient.

PMID- 22976704
TI  - Monostotic fibrous dysplasia of the mandible.
AB  - Fibrous dysplasia is a benign fibro-osseous disease that affects 1 or more bones.
      Deformities leading to aesthetic and functional disorders are observed in almost
      all cases. Plastic surgery is often recommended when the jaws are involved.
      Monostotic fibrous dysplasia of the mandible is an unusual manifestation of the
      disease that is usually benign, occurs in young individuals, and is managed by
      conservative curettage or debridement, such as surgical sculpting. The authors
      report a case of a 15-year-old patient with a large monostotic fibrous dysplasia
      located in the right mandible, which was treated by contouring bone. The lesion
      did not recur on follow-up for 4 years after the surgical procedure.

PMID- 22976705
TI  - Lingual schwannoma in pediatric patients.
AB  - We present the case of a 15-year-old boy who presented to our emergency
      department because of a soft lesion growing on the back of his tongue. On
      examination, a vegetant mass on the posteromidline lingual part of the body of
      the tongue was noticed: it was not painful, even if the boy reported discomfort
      because of its size; there was no bleeding or signs of infection. The magnetic
      resonance imaging showed the lesion as trilobated and capsulated, but was not
      diriment to define a diagnosis; excisional biopsy was performed under general
      anesthesia, and the mass was identified as a schwannoma. Schwannoma, or
      neurilemmoma, is a benign tumor originating from Schwann cells of the nerve
      sheath surrounding peripheral nerves. It is slow-growing, usually solitary, and
      encapsulated. Intraoral schwannomas are rare and account for 1% of lesions of the
      head and neck region. There is no sex predilection. The symptoms depend on size
      and location of the tumor. Recurrence is rare after complete surgical resection.
      The present study aimed to retrospectively describe our experience with a case of
      neurilemmoma of the tongue presenting in childhood, the diagnostic methods used,
      the surgical decision, and the treatment outcome and to analyze the data and
      review the literature available on this type of tumor. The etiology, clinical
      presentation, differential diagnosis, and management are discussed.

PMID- 22976706
TI  - Seasonal and yearly trends in cleft lip and palate in northeast Iran, 1989-2011.
AB  - Cleft lip and palate are the most common craniofacial congenital anomalies. The
      aim of this study was to detect the trend of seasonal and yearly fluctuations in
      the prevalence of cleft lip and palate birth in the northeast of Iran. MATERIALS
      AND METHODS: Data were obtained from 348 patients referred to the Cleft Lip and
      Palate Research Center of Mashhad Dental School during a 22-year period. Children
      with syndromes or patients from other areas of Iran were not included in this
      investigation. Recorded data included sex, type of cleft, date of birth, place of
      birth, and area of residence. Chi-squared test was used for comparisons. RESULTS:
      Without sex difference, the prevalence of all cleft types was more in winter and
      spring; however, there was no significant seasonal difference in birth dates of
      children with clefts (P = 0.777). This study showed that there was no significant
      difference in cleft types in both sexes(P = 0.113). Moreover, there appeared to
      be a reduction over time in the prevalence of all types of clefts, but there were
      fluctuations between years. CONCLUSIONS: This article suggests the influence of
      genetic and environmental factors other than season on the prevalence of
      orofacial clefts.

PMID- 22976707
TI  - Marsupialization as a treatment option for the odontogenic keratocyst.
AB  - BACKGROUND AND PURPOSE: The odontogenic keratocyst (OKC) is an unusual cyst with
      a high recurrence rate. The most common site for OKCs is by far the mandible. The
      best treatment of OKC remains controversial. Recurrence rates ranging anywhere
      from less than 10% to more than 60% have been reported. The aim of our study was
      to evaluate marsupialization as a treatment option for OKC. METHODS: We managed
      13 patients (8 male, 5 female) between the ages of 16 and 31 years (mean, 22.4 y)
      with biopsy-proven OKC. Radiographically, the patients' cyst sizes were between
      25 and 90 mm. Treatment consisted of marsupialization. We followed up with
      patients for a total duration of at least 60 months, and posttreatment visits
      were carried out at 6-month intervals. RESULTS: We documented cured or reduced
      cyst size with radiography. The odontogenic keratocyst resolved completely in 10
      patients, and the cyst walls shrank in 3 patients. The latter patients required a
      second operation to remove the associated impacted teeth. A histologic evaluation
      of 3 lesions showed metaplasia. Any case of recurring cysts was not seen during
      the entire follow-up period. CONCLUSIONS: Marsupialization is an effective and
      conservative treatment option for OKC. Nevertheless, future studies should
      conduct even longer follow-up periods to evaluate any recurrence of lesions.

PMID- 22976708
TI  - Severe symmetrical facial lipoatrophy in a patient with discoid lupus
      erythematosus.
AB  - Acquired partial lipodystrophy is a rare disorder, and it is characterized by the
      absence of subcutaneous fat from the face, the neck, the trunk, and the upper
      extremities. The etiology of acquired partial lipodystrophy includes scleroderma
      and discoid lupus erythematosus. Literature review reveals studies involving 10
      patients until today with lipoatrophy due to or after the onset of discoid lupus
      erythematosus; all are female patients. We want to report a young male patient
      with progressive symmetrical facial lipoatrophy. In addition, he has discoid
      lupus erythematosus and celiac disease. Fat grafting and adjuvant oral coenzyme
      Q10 tablets (Deka-none; Deka Pharmaceuticals, Istanbul, Turkey) were administered
      for treatment. To our knowledge, this case involves the first male patient in the
      literature presenting with symmetrical facial lipoatrophy with very prominent
      periorbital lipoatrophy and bitemporal hollowing symptoms.

PMID- 22976709
TI  - Intraoral transposition of pedicled temporalis muscle flap followed by zygomatic
      implant placement.
AB  - Despite the recent advances of sophisticated reconstructive surgical techniques,
      management of maxillectomy defects continues to be challenging. For a selected
      group of patients, who cannot sustain a sophisticated microsurgical
      reconstructive procedure, a prosthetic obturator is indicated to separate the
      oral cavity from the sinonasal cavities. After the development of the
      osseointegration concept, dental implants have proven to be indicated for the
      rehabilitation of patients who underwent maxillectomy. Recently, surgeons can use
      a computer-assisted software package, which enables them to insert implants after
      a detailed analysis of the residual bone. For some patients with limited amount
      of residual maxillary bone, unusual surgical sites such as the zygomatic complex
      have been tested. We introduce a successful 2-step surgical procedure using a
      pedicled temporalis muscle flap and zygomatic implant placement to reconstruct a
      maxillary defect after oncological resection.

PMID- 22976710
TI  - Atypical presentation of clear cell odontogenic carcinoma.
AB  - Clear cell odontogenic carcinoma (CCOC) is a rare malignant neoplasm of
      odontogenic origin. The usual clinical presentation of CCOC is a mass of
      progressive growth in the mandible sometimes accompanied with loss of teeth,
      pain, or bleeding. We describe a rare case of CCOC that showed an atypical
      presentation not previously described in the literature like a fast-growing
      painless mass in the retromolar area that reached a considerable size in a few
      days that caused obstruction of the airway. The presence of airway obstruction
      required immediate treatment, which consisted of a surgical excision of the tumor
      via a hemimandibulectomy. This clinical report highlights the possibility of
      odontogenic tumors presenting like a rapid-growing mass and the importance of
      clinical differential diagnosis of such presentation.

PMID- 22976711
TI  - A simple customized surgical guide for orthodontic miniplates with tube.
AB  - BACKGROUND: This article reports the use of a customized surgical guide for
      simple and precise C-tube plate placement with minimized incision. METHODS:
      Patients who were planning to have orthodontic miniplate treatment because of
      narrow interradicular space were recruited for this study. A combined silicone
      and stainless steel wire surgical guide for the C-tube was fabricated on the cast
      model. The taller wire of the positioning guide is used to accurately start the
      incision. The incision guide-wire position is verified by placing the miniplate
      on the coronal horizontal wire to confirm that the incision will coordinate with
      the screw holes. Because the miniplate is firmly held in place, there is no risk
      of the miniplate anchoring screws (diameter, 1.5 mm; length, 4 mm) sliding on the
      bone surface during placement with a manual hand driver. RESULTS: The surgical
      guide was placed on the clinical site, and it allowed precise placement of the
      miniplate with minimum incision and preventing from slippage or path-of-insertion
      angulation errors that might interfere with accurate placement. CONCLUSIONS:
      Customized surgical guide enables precise planning for miniplate positions in
      anatomically complex sites.

PMID- 22976712
TI  - Anterior tooth rehabilitation with frozen homogenous bone graft and immediately
      loaded titanium implant using computer-guided surgery.
AB  - Computed tomographic scanning is a precise, noinvasive surveying technique that
      enables the professionals to improve the precision of implant placement by
      building a prototype that allows the confection of surgical guides. The authors
      present a clinical case of anterior tooth rehabilitation with frozen homogenous
      bone graft and immediately loaded titanium implant using computer-guided surgery.
      A multislice computed tomography was realized, and a prototype was built. All the
      procedures were previously realized in the prototype before started in the
      patient. This technique allows a better surgical planning, makes the procedures
      more accurate, and reduces surgery time.

PMID- 22976713
TI  - Diagnosis and surgical management of nasopalatine duct cysts.
AB  - Nasopalatine duct cyst also known as nasopalatine cyst is a developmental,
      epithelial, non-neoplastic cyst that is considered to be the most common
      nonodontogenic cyst in the maxillofacial region. It is one of the many pathologic
      processes that may occur within the jaw bones, but it is unique in that it
      develops in only a single location--in the midline anterior maxilla. Nasopalatine
      cysts are usually asymptomatic and may be discovered during routine clinical
      and/or radiologic examination. The current study reports 18 cases of nasopalatine
      duct cyst that were diagnosed and treated at the Department of Oral and
      Maxillofacial Surgery at Ramadi Teaching Hospital, Anbar Province, Iraq. A
      correct diagnosis can only be made after proper clinical, radiographic, and
      histopathologic examination.

PMID- 22976714
TI  - Single-step nasal reconstruction with osteocutaneous forearm flap after total
      rhinectomy.
AB  - PURPOSE: Nasal defects resulting from tumor excision can be classified according
      to tissues involved, such as skin, cartilage, and bone. Although in the case of
      "simple" defects, reconstruction with loco-regional flap eventually associated
      with cartilage grafts can lead to satisfactory results; in the case of total or
      partial rhinectomy, a minimum of 3 and a maximum of 7 operations have to be
      performed in the current series to achieve an acceptable end result. We present
      the case of a total rhinectomy reconstruction in a single-step procedure with an
      osteocutaneous forearm free flap (RFOFF). CLINICAL REPORT: A 50-year-old man
      underwent total rhinectomy to excise a pathologically proven T4aN0 moderately
      differentiated squamous cell carcinoma of the nose; contemporary single-step
      reconstruction with an RFOFF was performed. Adjuvant radiotherapy was performed.
      RESULT: At 18 months of follow-up, the patient is free of disease and no
      postirradiation flap damage has been experienced; the flap notably did not appear
      to be bulky. CONCLUSIONS: We believe that the RFOFF is morphologically and
      functionally better than other flaps owing to its capability to adapt to the new
      environments of the nasal cavity, and to avoid, when possible, a three
      dimensional reconstruction of the same.

PMID- 22976715
TI  - Influence of loading and use of occlusal splint in implant-supported fixed
      prostheses.
AB  - The aim of the study was to assess the tensions generated in the long axis of the
      implants and the interimplants in the cervical, middle, and apical regions when
      subjected to different loads with or without interposition of the flat occlusal
      plane splint. A photoelastic model was made with 2 external hexagon implants
      located in the space corresponding to the second premolar and molar inferiors. A
      screw-retained metal superstructure was installed on the implants with a torque
      of 20 N.cm, and the set (photoelastic model with superstructure) were positioned
      in the circular polariscope in the dark-field configuration to observe the
      distribution of isochromatic fringes around the implants and interimplant areas.
      Photographic records were obtained before the application of the occlusal load
      with the following loading conditions: 300, 600, and 900 N, with and without
      interposition of the occlusal plane splint. The decrease in stress with the
      application of the flat occlusal plane splint became more evident after the
      application of the 600-N load. Generally, the major stress magnitude occurred in
      the cervical region for interimplant areas and in the apical region around
      implants. Use of occlusal splint in the loading of 300, 600, and 900 N reduced
      tension 33.22%, 66.66%, and 73.33%, respectively, in the samples. It can be
      concluded that the interposition of the occlusal plane splint caused a reduction
      in tension resulting from the simulation of occlusal overload.

PMID- 22976716
TI  - Giant cranial osteoma:  successful staged excision of the largest reported.
AB  - Craniofacial osteomas are benign, slow-growing neoplasms of the craniofacial
      region that are usually asymptomatic. Uncommonly, giant craniofacial osteomas may
      be symptomatic and cause serious morbidity including ophthalmologic problems,
      cerebral compression, pneumocephalus, and seizures. We present a case of a 15
      year-old Asian adolescent girl with a giant cranial osteoma (17.5 * 13.2 * 5 cm:
      significantly larger than previously reported). She also had multiple other
      synchronous giant osteomas of the face causing facial asymmetry. These osteomas
      were resected in a multiple-staged approach with a good aesthetic and functional
      outcome.

PMID- 22976717
TI  - Comprehensive review of hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen therapy involves inspiration of pure high pressure oxygen. For
      the past 20 years, administration of 100% high pressure oxygen and its potential
      benefits in management of diseases have been more clarified. Physiological
      advantages advocate HBO for the first-line treatment of several conditions. The
      specialty of craniofacial surgery is broad and deals with a diverse range of
      complications. The goal of this review is to help surgeons in their treatment
      planning by categorizing the indications of HBO therapy for oral and
      maxillofacial surgery. We also assess research data substantiating these
      indications where we believe basic physiological mechanisms and clinical
      evidences support further investigation on HBO efficacy to greater understanding
      of its potential benefit in oral and maxillofacial surgery.

PMID- 22976718
TI  - Use of deepithelialized medial sural artery perforator flap for the correction of
      postoncologic facial contour deformity.
AB  - We report a case of young patient with a postoncologic right buccomandibular
      defect in which the deepithelialized medial sural artery perforator flap was used
      to obtain a symmetric contour of the defective side. The aim of this study was to
      compare treatment strategies of facial contour deformities and to give detailed
      information about medial sural artery flap dissection with a clinical
      presentation.

PMID- 22976719
TI  - Does trauma etiology affect the pattern of mandibular fracture?
AB  - PURPOSE: The purpose of the present study was to evaluate the relationship
      between trauma etiologies and anatomic sites of mandibular fractures. PATIENTS
      AND METHODS: The sample was composed of all patients who sustained mandibular
      fractures during a 10-year period (2000-2009). The patients' age and gender were
      recorded; the relationships between fracture etiology and pattern of mandibular
      fracture were also analyzed. Data analysis included the chi2 test, the Fisher
      exact test, the t test, and logistic regression analysis. P < 0.05 was considered
      significant. RESULTS: Fall at ground level had a 9.64-fold risk of mandibular
      condylar fractures (odds ratio, 9.64; P < 0.001). No significant relationship
      existed between different etiologies and symphysis fracture. All of the
      etiologies had a low risk to mandibular body fractures (odds radio, <1; P <
      0.05). The occurrence of mandibular angle fractures was highly related to
      patients' age (P = 0.001). CONCLUSIONS: The pattern of mandibular fractures was
      highly related to patients' age and the different etiologies.

PMID- 22976720
TI  - Atypical traumatic subperiosteal orbital hematoma treated by surgical evacuation.
AB  - Subperiosteal orbital hematoma occurs rarely after blunt trauma. However, this is
      of importance, as this condition may cause ocular symptoms. The major
      characteristics of subperiosteal orbital hematomas are painful proptosis,
      downward displacement of the globe, absence of lid ecchymosis, chemosis without
      subconjunctival hemorrhage, and motility impairment. Visual impairment is known
      as a rarely presenting symptom. A 22-year-old male patient presented with right
      periorbital ecchymosis, swelling, and diplopia with upper lateral gaze
      limitation. Besides, the patient complained of lower visual field disturbance.
      Radiologic evaluation revealed traumatic subperiosteal orbital hematoma. The
      hematoma was evacuated through a lacerated wound on the right lateral eyebrow
      with additional incision. After the hematoma evacuation, the orbital symptoms are
      restored. Postoperative computed tomographic scans showed normally restored
      orbital space without any evidence of remnant hematoma or rebleeding. In case of
      subperiosteal hematoma, early detection and complete surgical evacuation is
      crucial for preventing possible complications and sequelae.

PMID- 22976721
TI  - Large unicystic ameloblastoma of the mandible:  management guided by biological
      behavior.
AB  - Ameloblastoma is a true neoplasm of odontogenic epithelial origin. It is a slow
      growing benign tumor of the jaw, and patients usually present late after the
      tumor achieves considerable size to cause facial disfigurement. Diagnosis mainly
      from tissue biopsy and radiograph findings does assist in differentiating between
      types of ameloblastoma. Unicystic ameloblastoma is a tumor with a strong
      propensity for recurrence. There is a difference in biological behavior between
      mural unicystic ameloblastoma and those which are simply cystic or show
      intraluminal proliferation. The challenges in the management of this tumor are to
      provide complete excision in addition to reconstructing the bony defect, to
      provide the patient with reasonable cosmetic and functional outcome. The authors
      report a case of a mural unicystic ameloblastoma in a 23-year-old man who was
      treated by partial resection of the mandible. Biomedical prototypes were used
      because they provide acceptable precision and are useful for treatment planning.

PMID- 22976722
TI  - Eustachian tube function following total laryngectomy.
AB  - OBJECTIVE: The function of the Eustachian tube has been investigated in various
      conditions. However, its status has not been evaluated in total laryngectomized
      patients. This study was designed to investigate short-term and long-term changes
      of the Eustachian tube that occur following total laryngectomy. METHOD: We
      enrolled a total of 53 patients who have undergone total laryngectomy in a
      tertiary referral center. These patients were divided into 2 groups, as those
      within the last 2 years after surgery (group 1) and those more than 2 years after
      surgery (group 2). In addition, 51 healthy volunteers were studied as a control
      group (group 3). We tested Eustachian tube function with P1, P2, and P3. P1 is
      the tympanometric measurement while resting. P2 is the tympanometric measurement
      after the Toynbee maneuver. P3 is the tympanometric testing after the Valsalva
      maneuver. To evaluate the functionality of the Eustachian tube, we used the P1-P2
      >10 daPa or Pmax - Pmin >15 daPa criteria. RESULTS: A statistically significant
      difference was not detected between Pmax - Pmin, P2, and P1-P2 values among the
      groups. Moreover, a statistically significant difference was also not detected
      between the right and left sides through the Pmax - Pmin values when assessing
      the groups among themselves. CONCLUSIONS: We determined that the functions of
      Eustachian tubes were not different between the patients who underwent total
      laryngectomy and the healthy volunteers at nearly the same age. The lack of
      active airflow in the upper respiratory tract following total laryngectomy has no
      effect on the function of the Eustachian tube in the short and long term.

PMID- 22976723
TI  - Diagnosis and treatment of ossified cephalhematoma.
AB  - Ossified cephalhematoma is a rare clinical entity. Even though cephalhematoma is
      frequently encountered, ossified cephalhematoma occurs only sporadically. We
      report a 13-week-old boy who was admitted to neurosurgery clinic with deformity
      of the skull. A plain skull radiograph showed radiolucent areas in the right
      parietal region. CT scan of the head showed thickened right parietal bone and a
      low-density lesion between bony layers. 3D CT of the skull showed bony protrusion
      of the right parietal bone. A cosmetic surgical procedure was performed for the
      patient, and biopsy of the bony lesion confirmed ossified cephalhematoma. We
      discuss diagnosis, pathogenesis, and treatment of ossified cephalhematoma.

PMID- 22976724
TI  - 18F-fluorodeoxyglucose-positive Warthin tumor in a contralateral cervical lymph
      node mimicking metastasis in tongue cancer staging with PET/CT.
AB  - We report 18F-fluorodeoxyglucose-positive Warthin tumor in a contralateral
      cervical lymph node mimicking metastasis in tongue cancer staging with positron
      emission tomography/computed tomography.

PMID- 22976725
TI  - Cutaneous Rosai-Dorfman disease recurrence in infraorbital region.
AB  - Rosai-Dorfman disease (RDD), also named sinus histiocytosis with massive
      lymphadenopathy, is a rare, idiopathic, and benign disorder that classically
      presents as a painless massive bilateral cervical lymphadenopathy. In cases of
      extranodal presentations, such as cutaneous RDD, it may not involve the classic
      manifestation. The diagnosis is usually made by histopathologic analysis. Surgery
      is suggested in the cases of significant cosmetic deformity or when there is
      fatal or functional obstruction. We reported a case of extranodal RDD that
      recurred in the infraorbital region postoperatively.

PMID- 22976726
TI  - Characteristics of bisphosphonate-related osteonecrosis of the jaw after kidney
      transplantation.
AB  - Renal transplantation is the definitive treatment of chronic renal failure, and
      osteoporosis in patients after renal transplantation is caused by the use of high
      dose corticosteroids, reduced renal function, and the use of immunosuppressant.
      While bisphosphonates inhibit osteoclastic activities, they are the drug of
      choice for the treatment and prevention of osteoporosis. Bisphosphonate-related
      osteonecrosis of the jaw (BRONJ) becomes a problematic issue. There are few
      reports on BRONJ in patients after renal transplantation, so many oral
      bisphosphonates commonly prescribed in patients after renal transplantation to
      prevent osteoporosis have no warning of BRONJ. We analyzed the records of
      patients with BRONJ from January 2009 to December 2010. Among the patients with
      BRONJ, we selected patients who underwent transplantation of the kidney.
      Demographic data, drug-related factors, and clinical characteristics were
      evaluated using chart review. A total of 128 patients were categorized as having
      BRONJ, and there were 3 patients with a history of kidney transplantation. The
      average age was 54.6 years, and 2 victims were men. All patients received oral
      bisphosphonates for more than 2 years (range, 2-7 y; average, 58.6 mo). All
      patients had hypertension, diabetes mellitus, history of high-dose
      corticosteroids, and taking immunosuppressant drugs. Bisphosphonate-related
      osteonecrosis of the jaw occurred in the maxilla in all patients, which is
      classified as stage 3 because of the involved sinus. Extraction was the main
      provoking factor in all patients. In conclusion, even at a relatively young age,
      BRONJ in the maxilla can be developed by intake of oral bisphosphonate after
      kidney transplantation. Dental care for patients before and after undergoing
      renal transplantation should be emphasized to reduce the risk of BRONJ.

PMID- 22976727
TI  - Myositis ossificans traumatica of the masticatory muscles.
AB  - Myositis ossificans traumatica (MOT) is a disease in which muscular ossification
      develops following trauma. Almost all cases of MOT are found in skeletal muscle.
      The authors report in a 39-year-old man MOT involving several muscles in the head
      and neck, namely, bilateral masseter muscles, the left temporal muscle, the left
      lateral pterygoid muscle, and the left frontal muscle. Involvement of the lateral
      pterygoid muscle is especially rare.

PMID- 22976728
TI  - Recurrent mandibular dislocation treated by eminectomy.
AB  - Mandibular dislocations present with frequency; when they are recurrent and
      sustained over time, surgical treatment is indicated. Although different
      therapeutic techniques exist, the eminectomy is one of the most often applied. In
      this investigation, 3 cases are described where the bilateral eminectomy was
      performed for recurrent mandibular dislocation with 5 years of duration. No
      dislocation recurrence, postoperative pain, or functional alterations were
      observed in any of the patients. The bilateral eminectomy is a well-known
      procedure described in the literature, with good scientific support and constant
      modifications to optimize its indications and results. Compared with the results
      from other investigations, it is concluded that treatment with a bilateral
      eminectomy can be applied safely in cases of recurrent mandibular dislocations.

PMID- 22976729
TI  - Two-stage total prosthetic reconstruction of temporomandibular joint in severe
      and recurrent ankylosis.
AB  - Temporomandibular joint ankylosis is a devastating condition for the patient
      associated with both functional disability and aesthetic deformities. Various
      techniques have been described in the literature to overcome this problem;
      however, there is still a high risk of reankylosis in patients undergoing
      multiple temporomandibular joint operations, severe heterotopic ossification, and
      fibrosis of the soft tissues. This study includes 5 patients with severe and
      recurrent ankylosis. Two-stage reconstruction with excision of the bony mass and
      placement of a distraction device in the first stage, followed by gradual
      distraction of soft tissues, and placement of a total joint prosthesis in the
      second stage were performed in all patients. The 2-step approach helps to
      overcome the fibrosis and adhesions in the soft tissues and allows placing an
      implant with a higher ramus component. This approach seems to be a useful and
      effective technique for the management of such patients with high risk of
      reankylosis.

PMID- 22976730
TI  - Compromised primary implant stability.
AB  - The aim of this study was to evaluate implants installed with compromised primary
      stability associated or not with polylactide and polyglycolide copolymer
      (PLA/PGA). Two 0.4-mm overdrilled defects (3 mm in diameter and 6 mm long) were
      produced in the right tibia of 25 rabbits. Half of the defects were left
      untreated, and the other half was filled with PLA/PGA. Implants of 2.6 mm in
      diameter and 6 mm long were placed into all defects. Animals were killed at 5,
      15, 40, and 60 postoperative days, and biomechanical analysis (torque-reverse),
      histomorphometry, and immunohistochemistry (osteoprotegerin, receptor activator
      of NF-kappaB ligand [RANKL], osteocalcin, and collagen-1 [COL-I] staining) were
      performed. All the implants achieved osseointegration. There were no
      statistically significant differences in the torque-reverse and in linear contact
      extension between bone tissue and implant surface and no statistically
      significant difference in osteoprotegerin, RANKL, osteocalcin, and collagen-1
      expression between the studied groups in all studied periods (P > 0.05). We can
      conclude that osseointegration can occur in compromised primary implant stability
      situations, and the addition of PLA/PGA did not improve the osseointegration
      process in this experimental model.

PMID- 22976731
TI  - The contribution of underwater kicking efficiency in determining "turning
      performance" in front crawl swimming.
AB  - AIM: The aim of this study was to analyze the effects: 1) of maximal velocity
      (vout max) and acceleration (aout max) attained during the turn; 2) of
      deceleration (-aglide) and glide efficiency (GE) in the gliding phase after the
      turn; and 3) of the efficiency (hF) of the dolphin kick in determining the
      velocity and acceleration in the first 5 and the following 10 m after a turn (v5,
      v5-15, a5 and a5-15) in a 100 m simulated front crawl race. METHODS: The
      experiments were conducted on 13 swimmers (7M/5F) and all the above mentioned
      parameters were derived from underwater kinematical analysis. RESULTS: The 100 m
      times were smaller the larger v5, v5-15, a5 and a5-15. In turn, v5, v5-15, a5 and
      a5-15 were significantly related to vout max and aout max as well as to etaF and
      GE (R>0.57, P<0.05). CONCLUSION: Data reported in this study indicate that in the
      first 5-15 m after the turn, velocity is essentially sustained by the force
      generated by the swimmer on the pool wall but also indicate the importance of an
      efficient dolphin kick (and of a streamlined glide) in determining the values of
      velocity and acceleration in this phase of the race.

PMID- 22976732
TI  - Development of non-exercise based VO2max prediction equation in college-aged
      participants in India.
AB  - AIM: The purpose of this study was to develop a linear regression model to
      predict treadmill VO2max scores using non-exercise data. METHODS: In this cross
      sectional study, one hundred twenty college-aged participants (60 male, 60
      female, mean age 22.02+/-2.29 years) voluntarily participated and successfully
      completed a maximal graded exercise test (GXT) on a motorized treadmill to assess
      VO2max (mean+/-SD; 2.05 L.min-1+/-1.03 L.min-1). The maximal treadmill GXT
      required participants to exercise to volitional fatigue. RESULTS: Relevant non
      exercise data included a mean (+/-SD) perceived functional ability (PFA) score,
      and physical activity rating (PA-R) score, body surface area (BSA) of 14.6+/-3.9,
      2.97+/-1..75, 1.66+/-0.17, respectively. Multiple linear regression generated the
      following regression equation (R=0.899, R2=0.805, adjusted R2=0.799, SEE=0.426
      L.min-1): VO2max (L/min)=-1.541+1.096 (gender, 1=male, 0=female) +.081 (PFA)
      +1.084(BSA). Each predictor variable was statistically significant (P<0.05) with
      beta weights for gender, PFA, BSA, PA-R, and equal to (-0.518), (0.255), (0.228),
      (0.092), percent body fat (-0.003), respectively. The accuracy of the model was
      evaluated by conducting a cross-validation analysis (N.=18). CONCLUSION: This
      study provides a N-EX regression prediction model that yields results and also
      provide a convenient and efficient tool that estimate VO2max in healthy college
      aged participants in India.

PMID- 22976733
TI  - Ratings of perceived exertion in adults with chronically physical challenges.
AB  - AIM: The purposes of this study were to investigate: the relationship between
      ratings perceived exertion (RPE) and percentage of maximal oxygen uptake
      (%VO2max) during submaximal exercise; the influence of daily physical activities
      on RPE; and the influence of aerobic fitness on RPE. METHODS: The participants
      were thirty-eight adults with chronically physical challenges. Submaximal
      exercise testing was conducted to estimate VO2max. The participants themselves
      declared their perceived exertion just before the end of the exercise testing by
      indicating the Borg's 6-20 RPE scale. Measurement of continuous heart rates was
      employed for measurement of the intensity of daily physical activities. The
      relationship between %VO2max and RPE was analyzed. RESULTS: There was a
      significant correlation between %VO2max and RPE only in the active men who did
      daily aerobic physical activities with intensity of 30%HRR and more (N.=9,
      r=0.74, P=0.02). In the good fitness groups of both women and men, the actual
      %VO2max in 11 out of 12 participants was lower than the reference value of
      %VO2max of the RPE while the opposite trend was found in poor aerobic fitness
      group. CONCLUSION: Our results recommend that RPE should be used together with
      objective physiological variables such as HR for assessment of exercise intensity
      in people with chronically physical challenges, especially who are low in aerobic
      fitness or who are inactive.

PMID- 22976734
TI  - Is there a relationship between the total volume of load lifted in bench press
      exercise and the rating of perceived exertion?
AB  - AIM: The purpose of the study was to investigate the relationship between the
      total volume of load lifted (TVLL) and the rating of perceived exertion (RPE)
      measures during different resistance training (RT) schemes using the bench press
      exercise. METHODS: The present study was divided into two experiments. In the
      first experiment, 18 healthy men performed three different RT schemes: a strength
      oriented scheme (SS), a muscular endurance oriented scheme (ES) and a hypertrophy
      oriented scheme (HS). TVLL was calculated for each scheme. Mean-RPE and session
      RPE were assessed. In the second experiment, 23 men performed two resistance
      exercise bouts at different intensities (50%-1RM and 75%-1RM) with matched TVLL.
      Mean-RPE and session-RPE were also assessed. RESULTS: SS and HS showed higher
      TVLL and greater RPE scores as compared to ES (P<0.05). No significant difference
      was observed between SS and HS. It was verified significant positive correlations
      between TVLL and session-RPE (SS r=0.63, HS r=0.64, ES r=0.56; P<0.05), and
      between mean-RPE and TVLL (SS r=0.55, HS r=0.52, ES r=0.47; P<0.05) for all
      schemes. No differences were observed for mean-RPE, session-RPE and TVLL between
      the 50%-1RM and 75%-1RM. Significant positive relationships between TVLL and
      session-RPE (50%-1RM r=0.61, 75%-1RM r=0.66; p<0.05) and between TVLL and mean
      RPE (50%-1RM r=0.51, 75%-1RM r=0.49; P<0.05) were observed. CONCLUSION: The
      results of this study have shown that the TVLL in RT influences RPE measures.
      These findings corroborates the existence of a relationship between total work
      performed (external training load) and perception of effort (internal training
      load).

PMID- 22976735
TI  - BMD in elite female triathletes is related to isokinetic peak torque without any
      association to sex hormone concentrations.
AB  - AIM: Female endurance athletes suffering from low energy availability and
      reproductive hormonal disorders are at risk of low BMD. Muscle forces acting on
      bone may have a reverse site-specific effect. Therefore we wanted to test how BMD
      in female elite triathletes was associated to isokinetic peak torque (IPT) and
      reproductive hormone concentrations (RHC). A possible effect of oral
      contraceptives (OCON's) is taken into consideration. METHODS: Eight female elite
      triathletes (training 8-24 hrs/wk) and seven sedentary controls, age 21-37 years,
      participated. Total body and regional BMD (g.cm-2) were measured by DXA. IPT were
      measured during knee extension, and trunk extension and flexion (Nm). Serum RHC
      and biochemical bone markers were evaluated. Energy balance was estimated from 7
      days training-and weighed food records. RESULTS: Despite a high training volume,
      BMD in triathletes was not higher than in controls. In triathletes trunk flexion
      IPT, but not RHC, was a strong predictor of BMD in both total body and femur
      (0.70<r<0.86, P<0.05). RHC did not differ between triathletes and controls, but
      in OCON-users RHC (in controls also BMD) seemed lower than in non-users. Energy
      intake in triathletes corresponded to 65-111% of energy expenditure. CONCLUSION:
      The association between trunk flexion IPT and BMD in triathletes supports the
      theory that muscle forces are important osteogenic factors. The findings of no
      correlation between RHC and BMD, but a tendency to a negative effect of low RHC
      only in OCON-controls, might indicate that in female athletes muscle forces
      acting on bone potentially counteract a negative effect of reproductive hormonal
      disorders on BMD.

PMID- 22976736
TI  - Nutritional practices of elite swimmers during an intensified training camp: with
      particular reference to antioxidants.
AB  - AIM: Athletes should match their energy intake with expenditure in order to
      maintain lean body mass. It is also important to consume adequate amounts of
      antioxidant vitamins and minerals to maintain health. METHODS: To assess the
      dietary habits of six nationally ranked Australian swimmers physical training
      load and dietary intake (24 h food recall) and were recorded on a daily basis
      during a 4 day intensive physical training period. RESULTS: The results showed no
      significant difference between energy intake and expenditure (P=0.58) or the
      amount of carbohydrate consumed (P=0.14) compared to the Australian recommended
      daily intake (RDI). Athletes reported a significantly greater intake of vitamin A
      (P<0.01), vitamin C (P<0.01), vitamin E (P<0.01) and protein (P<0.01) than the
      RDI. CONCLUSION: It was concluded that these elite swimmers have an adequate
      dietary intake to allow for optimal physical training and performance.

PMID- 22976738
TI  - The Swiss Army physical fitness test battery predicts risk of overuse injuries
      among recruits.
AB  - AIM: The aim of this study was to quantify the discriminative power of physical
      performance tests to recognize conscripts with enhanced risk of acute and overuse
      injuries in specific, physically demanding occupational specialties of the Swiss
      Army. The five performance tests investigated represent the Swiss Army Physical
      Fitness Test Battery. METHODS: Physical fitness performances were assessed during
      recruitment procedures prior to military service, and injury occurrences were
      assessed during 18 weeks of boot camp. Complete fitness and injury data of 459
      volunteers from four military occupational specialties were collected.
      Discriminative power of volunteers' aerobic endurance capacity, trunk muscle
      fitness, muscle power of upper and lower extremities, and balance for predicting
      risk of acute injuries and for predicting risk of overuse injuries was calculated
      using receiver operating characteristic curve analysis. RESULTS: The presented
      fitness tests had no discriminative power for predicting the risk of acute
      injuries. However, the trunk muscle fitness test was discriminative in predicting
      overuse injuries in all four military occupational specialties, progressive
      endurance run in three, balance test in two, and standing long jump in one. Only
      the seated shot put had no significant power for predicting overuse injuries in
      all four study groups. However, for different occupational specialties, different
      fitness parameters were discriminative to predict overuse injuries. CONCLUSION:
      It is possible to conclude that the fitness tests used allow detection of
      conscripts with enhanced overuse injury risk in physically demanding occupational
      specialties and therefore provide an indicator to select suitable personnel for
      physically demanding jobs in a military organization.

PMID- 22976737
TI  - The influence of time-of-day variation and loading on the aponeurosis plantaris
      pedis: an ultrasonographic study.
AB  - AIM: The aim of this paper was to investigate the effect of time-of-day on the
      thickness of the the aponeurosis plantaris pedis, and to examine the acute
      effects of high-load strength training and long distance running on the thickness
      of the aponeurosis plantaris pedis. METHODS: Proximal aponeurosis plantaris pedis
      thickness was assessed with a 13-MHz linear-array transducer. In sub-study 1, ten
      participants (ten aponeurosis') were measured five times during 24 hours. In sub
      study 2, ten participants (ten aponeurosis') were measured just before,
      immediately after and again three hours after 3x12 unilateral heel-rises. In sub
      study 3, 11 healthy experienced runners (11 aponeurosis') were measured just
      before, immediately after and two hours after a 15km run. The average thickness
      of three scans of each foot was used in the analysis. The data was analysed using
      repeated measures one-way ANOVA. RESULTS: The mean thickness of the aponeurosis
      plantaris pedis' fluctuated significantly during the 24 hours (p=0,02), but it
      did not change in relation to the high-load strength training (p=0,86) or 15km of
      running (p = 0,70). CONCLUSION: High-load strength training and long distance
      running do not induce changes in the thickness of the aponeurosis plantaris
      pedis. Time-of-day influences the thickness of the aponeurosis plantaris pedis,
      but the changes are not larger than measurement uncertainty.

PMID- 22976739
TI  - Effects of 12 weeks of aerobic exercise on body composition and vascular
      compliance in obese boys.
AB  - AIM: This study tested the hypothesis that 12 weeks of air board exercise would
      enhance cardiorespiratory fitness and vascular compliance and reduce % body fat
      in obese Korean boys. METHODS: Twenty-two obese boys (>30% body fat) were
      studied. They were divided into 2 groups- an aerobic exercise group (N.=12),
      which trained 3 days/week, 50 min/day for 12 weeks, and a control group (N.=10).
      Control subjects only performed activities involved in their physical education
      classes. Body composition, cardiovascular fitness (20 m multistage endurance test
      performance) and vascular compliance were assessed before and after the
      completion of exercise training. RESULTS: The % changes in body fat (-4.6+/-0.9
      vs. -1.5+/-1.0%), fat mass (-5.4+/-1.5 vs. -0.1+/-1.6%) and performance on the
      cardiovascular fitness test (14.3+/-2.5 vs. 3.7+/-1.6%) were greater in the
      exercise group than in the controls Compared to controls, % increases in vascular
      compliance were greater in the arms and legs of the exercise group (left arm:
      2.8+/-0.5 vs. 2.0+/-2.9%; left leg: 2.6+/-1.2 vs. -0.5+/-2.0%; right arm: 2.9+/
      0.9 vs. 0.3+/-2.9%; right leg: 4.8+/-1.8 vs. 1.5+/-2.0%). CONCLUSION: Results
      suggest that exercise training can reduce % body fat and enhance vascular
      compliance in obese male adolescents; changes that may reduce the risk for later
      development of cardiovascular disease.

PMID- 22976740
TI  - Risks factors for recurrent neurological decompression sickness in recreational
      divers: a case-control study.
AB  - AIM: Individual or environmental factors that predispose to the recurrence of
      neurological decompression sickness (DCS) in scuba divers are not known and
      preventive measures designed to mitigate the risk of a subsequent episode remain
      empirical. The aim of this controlled study was to examine some potential risk
      factors predictive of recurrent DCS event that may lead to practical
      recommendations for divers who wish to continue diving after an initial episode.
      METHODS: Age, gender, diving experience, presence of a large right-to-left shunt
      (RLS) and diving practice following post-DCS resumption were evaluated as
      potential predictors of a further DCS in recreational divers admitted in our
      hyperbaric facility over a period of 12 years. RESULTS: Twenty-four recurrent
      cases and 50 divers treated for a single DCS episode which continued diving were
      recruited after review of medical forms and follow-up interview by telephone.
      After controlling for potential confounding variables between groups,
      multivariate analysis revealed that experienced divers (OR, 3.8; 95%CI, 1.1-14;
      P=0.03), the presence of large RLS (OR, 5.4; 95%CI, 1.5-19.7; P=0.006) and the
      lack of changes in the way of diving after prior DCS (OR, 8.4; 95%CI, 2.3-31.1;
      P=0.001) were independently associated with a repeated episode. CONCLUSION: The
      findings highlight the importance for divers to adopt conservative dives profiles
      or to use preferentially oxygen-enriched breathing mixtures after an initial DCS.
      Closure of a documented RLS through a large patent foramen ovale as a secondary
      preventive procedure for individuals that cannot adapt their diving practice
      remains debatable.

PMID- 22976741
TI  - Impact of a physical activity program on cerebral vasoreactivity in sedentary
      elderly people.
AB  - AIM: The aim of the present study was to determine the effect of a physical
      activity program on the hemodynamic response of the brain (vasoreactivity) in
      elderly people. METHODS: Eighteen men and 25 women (aged 62-67 years) were
      randomly assigned to an experimental (EXP, N.=22, 12 women) and a control (CON,
      N.=21, 13 women) group. Subjects in EXP group were required to complete a 7-month
      program based on aerobic training (3-4 sessions/weekd, 50 min/session, 3-4
      sessions/week, at 70% maximum heart rate). Transcranial Doppler ultrasound was
      used to examine the cerebral blood flow response to hypercapnic and hypocapnic
      stimuli. We also determined blood pressure, total serum cholesterol, HDL and LDL
      cholesterol, and triglycerides, and conducted an aerobic capacity test (the 2.4
      Km walking test). RESULTS.Brain vasomotor reactivity improved in the EXP group,
      reflected by a higher blood flow velocity in the middle cerebral artery (MCA) in
      both cerebral hemispheres in response to hypercapnia (induced by breath holding)
      (P<0.05). Subjects in EXP group also improved the cardiovascular profile aerobic
      physical condition (P<0.001) in terms of reduced arterial pressure, total
      cholesterol and triglyceride levels. CONCLUSION: Our findings indicate that
      cerebral vasoreactivity in elderly may be improved by undertaking an aerobic
      exercise program.

PMID- 22976742
TI  - Thoracic kyphosis comparisons in adolescent female competitive field hockey
      players and untrained controls.
AB  - AIM: The aim of this study was to compare the thoracic kyphosis angles of
      adolescent female field hockey players and non-athletes and to examine the
      relationship between the thoracic kyphosis and training regimes in hockey.
      METHODS: Seventy-four female participants including 37 field hockey players (mean
      age 19.03 +/-1.24 years) and 37 non-athletes (mean age 18.21+/- 1.22) were
      recruited in this cross-sectional study. The hockey players met a minimum
      criterion of 3 years of experience in the Iranian first division female hockey
      league. The thoracic kyphosis degree was measured between T1-T12 using a non
      invasive flexible ruler. RESULTS: A significant difference in the thoracic
      kyphosis degree between athletes (M=41. 71 degrees , SD=5.38 degrees ) and non
      athletes (M=36.72 degrees , SD=6.01 degrees ); t (72)=3.76, P=0.001 was revealed.
      The magnitude of these differences in the means was very large (eta
      squared=0.016). There was a moderately positive correlation between the athletic
      history (number of years of hockey participation) and thoracic kyphosis, r=0.36,
      N.=37, P=0.031. However, the relationship between the cumulative training
      exposure (yearly training hours) and the degree of thoracic kyphosis was not
      significant. CONCLUSION: Thoracic kyphosis was significantly increased in
      adolescent female field hockey players and was found to be associated with the
      cumulative number of years of hockey participation. These results suggest a
      possible association between the semi-crouched posture in field hockey and
      thoracic kyphosis in elite adolescent athletes The results also suggest that
      number of years of field hockey participation is a determinant in the increased
      kyphosis.

PMID- 22976743
TI  - Predicting athletic success motivation using mental skin and emotional
      intelligence and its components in male athletes.
AB  - AIM: The aim of this study was to predict athletic success motivation by mental
      skills, emotional intelligence and its components. METHODS: The research sample
      consisted of 153 male athletes who were selected through random multistage
      sampling. The subjects completed the Mental Skills Questionnaire, Bar-On
      Emotional Intelligence questionnaire and the perception of sport success
      questionnaire. Data were analyzed using Pearson correlation coefficient and
      multiple regressions. RESULT: Regression analysis shows that between the two
      variables of mental skill and emotional intelligence, mental skill is the best
      predictor for athletic success motivation and has a better ability to predict the
      success rate of the participants. Regression analysis results showed that among
      all the components of emotional intelligence, self-respect had a significantly
      higher ability to predict athletic success motivation. CONCLUSION: The use of
      psychological skills and emotional intelligence as an mediating and regulating
      factor and organizer cause leads to improved performance and can not only can to
      help athletes in making suitable and effective decisions for reaching a desired
      goal.

PMID- 22976744
TI  - Superimposed electrical stimulation comfortably improves the endurance of maximal
      voluntary contractions.
AB  - AIM: Electrical stimulation has shown to improve muscle endurance in sub-maximal
      contractions but sessions were painful due to the electric stimuli parameters.
      Therefore, the present study tested the effects of the superimposed electrical
      stimulation technique using comfortable current on endurance in repetitions of
      maximal voluntary contraction. METHODS: Seventeen young healthy subjects
      performed fifty maximal voluntary contractions of the triceps brachii in two
      conditions of contraction (voluntary vs. voluntary + superimposed electrical
      stimulation). RESULTS: Peak force and force-time integral were consistently
      decreased in the voluntary muscular contraction condition after the 20th - 30th
      trials whereas they were maintained in the superimposed electrical stimulation
      condition (P<0.05) until the end of the fifty trials. CONCLUSION: The
      superimposition of neuromuscular electrical stimulation extends the muscle
      ability to repeat maximal voluntary contractions. The present results also
      evidenced the ability of the superimposed electrical stimulation technique to
      make the mechanisms of muscle central fatigue inefficient.

PMID- 22976745
TI  - Cytokines and cellular inflammatory sequence in non-athletes after prolonged
      exercise.
AB  - AIM: The goal of the study was to clarify the sequence of cytokines and
      inflammatory cells in non-athletes performed an intense running exercise.
      METHODS: Sixteen young healthy men participated in the exercise trial that
      involved 90-min run at 65% VO2max. RESULTS: The plasma concentrations of anti
      inflammatory cytokines IL-4, IL-6 and IL-10 increased immediately after exercise
      simultaneously with number of white blood cells. Between IL-6 and IL-10, and
      neutrophils the relationships were observed. The correlation value for IL-6 and
      neutrophils was 0.775 whereas for IL-10 and neutrophils was 0.506. The
      proinflammatory cytokines IL-1beta and TNFalpha were detected at 6 h after
      exercise and moderately correlated with monocytes count. The high level of
      proinflammatory cytokines, monocytes and creatine kinase (CK) remained until 48 h
      rest. The CK activity significantly correlated with IL-1beta (r=0.578) and
      TNFalpha (r=0.452), and also with monocytes count (r=0.439). CONCLUSION: The
      results have shown that: 1) exercise induces anti-inflammatory cytokines
      production first and then proinflammatory cytokines; and 2) prolonged
      proinflammatory response is closely related with muscle damage present.

PMID- 22976746
TI  - Effects of prolonged intensive training on the resting levels of salivary
      immunoglobulin A and cortisol in adolescent volleyball players.
AB  - AIM: Concerns have been raised regarding the effects of prolonged intensive
      training on adolescent athletes. This study investigated the differences in
      mucosal immune functions and stress responses between intensively trained male
      adolescent volleyball players and age-matched sedentary controls. METHODS: Twelve
      male volleyball players (16.5 [0.7] years of age) and sixteen healthy sedentary
      male volunteers (17.1 [0.6] years of age) participated in this study. Volleyball
      players were engaged in regular and year-round training. Unstimulated saliva
      samples were collected from volleyball players during the high-intensity training
      period and from the counterparts at the same timepoints after at least 18 hours
      of rest. Concentrations of salivary total protein, secretory immunoglobulin A
      (SIgA), cortisol, and lactoferrin were measured. RESULTS: Results of this study
      revealed that the SIgA concentrations and the ratio of SIgA/total protein in
      volleyball players were significantly lower compared with those in sedentary
      controls. However, the salivary cortisol concentrations and the ratio of
      cortisol/total protein in volleyball players were markedly higher compared with
      those in sedentary controls. No significant difference was observed in
      lactoferrin levels between volleyball players and sedentary controls. CONCLUSION:
      The findings of this study suggest that the prolonged intensive training may
      elicit a sustained stress and induce a suppressive effect on mucosal immunity in
      regularly and intensively trained adolescent athletes.

PMID- 22976747
TI  - A magnetic cell-based sensor.
AB  - Cell-based sensing represents a new paradigm for performing direct and accurate
      detection of cell- or tissue-specific responses by incorporating living cells or
      tissues as an integral part of a sensor. Here we report a new magnetic cell-based
      sensing platform by combining magnetic sensors implemented in the complementary
      metal-oxide-semiconductor (CMOS) integrated microelectronics process with cardiac
      progenitor cells that are differentiated directly on-chip. We show that the
      pulsatile movements of on-chip cardiac progenitor cells can be monitored in a
      real-time manner. Our work provides a new low-cost approach to enable high
      throughput screening systems as used in drug development and hand-held devices
      for point-of-care (PoC) biomedical diagnostic applications.

PMID- 22976748
TI  - PFGE and AFLP genotyping of Staphylococcus aureus subsp. anaerobius isolated from
      goats with Morel's disease.
AB  - Staphylococcus aureus subsp. anaerobius is the etiological agent of the Morel's
      disease in sheep and goats. The disease presents with subcutaneous abscesses,
      located mainly in the superficial lymph nodes. Forty-one isolates of S. aureus
      subsp. anaerobius were collected from two outbreaks of the Morel's disease in
      Poland in years 2006-2008. Analysis of DNA SmaI digests by PFGE showed that 35 of
      41 isolates belonged to the same PFGE type, identical to the type strain of S.
      aureus subsp. anaerobius ATCC 35844, confirming high level of clonality of the
      species. The DNA patterns of the remaining identical 6 isolates, different from
      the reference strain only by two bands, were found closely related. Genotyping
      performed with AFLP technique revealed two clonal groups including 16 and 25
      isolates, respectively. The study indicated that AFLP technique might be a better
      discriminatory tool for genetic analysis of S. aureus subsp. anaerobius isolates,
      when compared to PFGE.

PMID- 22976749
TI  - Location, location, location-gene expression studies of brainstem ganglioglioma:
      a rare tumor in a very rare location.

PMID- 22976750
TI  - The Mousterian child from Teshik-Tash is a Neanderthal: a geometric morphometric
      study of the frontal bone.
AB  - In the 1930s subadult hominin remains and Mousterian artifacts were discovered in
      the Teshik-Tash cave in South Uzbekistan. Since then, the majority of the
      scientific community has interpreted Teshik-Tash as a Neanderthal. However, some
      have considered aspects of the morphology of the Teshik-Tash skull to be more
      similar to fossil modern humans such as those represented at Skhul and Qafzeh, or
      to subadult Upper Paleolithic modern humans. Here we present a 3D geometric
      morphometric analysis of the Teshik-Tash frontal bone in the context of
      developmental shape changes in recent modern humans, Neanderthals, and early
      modern humans. We assess the phenetic affinities of Teshik-Tash to other subadult
      fossils, and use developmental simulations to predict possible adult shapes. We
      find that the morphology of the frontal bone places the Teshik-Tash child close
      to other Neanderthal children and that the simulated adult shapes are closest to
      Neanderthal adults. Taken together with genetic data showing that Teshik-Tash
      carried mtDNA of the Neanderthal type, as well as its occipital bun, and its
      shovel-shaped upper incisors, these independent lines of evidence firmly place
      Teshik-Tash among Neanderthals.

PMID- 22976751
TI  - [The Mexican Board of Pathology: microscopy examination before and after digital
      microscopy].
AB  - INTRODUCTION: The examination carried out by the COMMAP for the certification
      process assessed pathologist formed in dissimilar institutions. In 2007 COMMAP's
      governing body in turn, decided to digitize it. The purpose of this study is to
      investigate whether the conversion to virtual slides in the microscopy section,
      compared with the traditional have had an impact on the scores of the candidates.
      METHOD: The slides were scanned with high resolution. The virtual microscope is a
      standard computer screen where there is a program (Aperio Scope Image Viewer)
      that can display the scanned slides. The results of the microscopy section of the
      past nine years were compared; two groups were formed: 1) those without digitized
      examination, and 2) with it. The results were compared by Student t-test and Mann
      Whitney. RESULTS: Of a 461 results 240 belonged to the first group and 221 to the
      second one. On a scale of 1-10, the average scores were 6.6 and 6.8, respectively
      (p > 0.6 and > 0.5).The minimum and maximum scores were also similar in each
      group. CONCLUSIONS: According to the results, the digitized exam in the COMMAP's
      certification process shows no difference between the digitized and the
      conventional versions.

PMID- 22976752
TI  - [Metaplastic breast cancer: clinical factors].
AB  - BACKGROUND: metaplastic breast carcinoma (MBC) is uncommon, characterized by a
      heterogeneous mixture of histologic characteristics. OBJECTIVE: evaluate clinical
      and pathological characteristics in a population of patients with MBC in a
      reference center. MATERIALS AND METHODS: retrospective analysis of cases
      diagnosed with MBC at INCAN database from 2005-2011 was performed. Univariate
      assessment of clinical variables and their impact on disease free survival(DFS)
      and overall survival (OS) were evaluated. RESULTS: the records of 20 patients
      were identified. Median age was 49.5 (range: 33-75). Clinical stages at diagnosis
      were 6 I-II (30%) and 14 III-IV (70%). Three year OS was 52.1%. Patients< 40
      years had an OS of 32.8 months vs. >= 40 years of 17.8 (p = 0.097). OS in stage I
      II was 13.5 months vs. 23.3 months in III-IV (p = 0.99). Those who received
      neoadjuvant therapy had an OS of 26.57 vs. 14.36 in those who did not(p = 0.54).
      Those who received adjuvant therapy had an OS of 31.2 months vs. 11.15 in those
      who did not (p = 0.036). CONCLUSIONS: MBC has bad prognosis, nevertheless, age <
      40 years and hormone receptor positivity, as well as adjuvant treatment seems to
      be factors that have an influence OS.

PMID- 22976753
TI  - [Trends in mortality by burns in Mexico, 1979-2009].
AB  - OBJECTIVE: To describe the trends in burn-related mortality rates in Mexico from
      1979-2009. METHODS: Burn-related mortality standardized rates and trends were
      estimated from official mortality data in Mexico. Variables included were:age,
      sex, federal state and year of death. RESULTS: From 1979-2009, 33,333 burn
      related deaths were registered. During this period, the burn-mortality rate
      decreased, stating from a rate of 2.32/100,000 in 1979 and dropping to
      0.72/100,000 in 2007, but in 2008 and 2009 the mortality rates occurred in the
      states of Baja California, Chihuahua, Baja California Sur,Sonora and Durango, all
      of these states in the northwest of Mexico. Men were twice as likely as women to
      die from burns. CONCLUSIONS: Mortality caused by burns in Mexico presents a
      descendent tendency in most of the states of the Country, with the exception of
      the northwest region, which may be related to the lack of specialized units in
      the treatment of burn distance between the population centers and the specialized
      attention units.

PMID- 22976754
TI  - [Assessment of neoplastic pancreatic focal injury by multidetector computed
      tomography].
AB  - INTRODUCTION: pancreatic focal neoplastic lesions (PFNL) should be characterized
      through image methods to differentiate from no neoplastic lesions, suggesting one
      or more probable diagnosis, and staging of malignant lesions, in order to help
      define the estrategy of medial or surgical management. The multidetector computed
      tomography (MDCT) offers multiple properties and advantages that enable adequate
      characterization of the PFNL. The objective of this study is to evaluate de
      usefulness of MDCT in characterizing PFNL. MATERIAL AND METHODS: a descriptive,
      retrospective caseseries study has been conducted. It consisted of reviewing MDCT
      studies in which PFNL were found, over a period of 4 years 11 months from January
      2006 to November 2010. RESULTS: we obtained 54 cases of PFNL which were
      characterized by MDCT; 75.9% for a specific diagnosis, and were categorized as
      indeterminate 24.1%, considering more than one possible diagnosis. The most
      frequent PFNL type was pancreatic ductal adenocarcinoma in 51.9%. Pancreatic
      cystic neoplasms accounted for 16.7%. CONCLUSIONS: MDCT is useful for identifying
      and characterizing LFNP, this means the possibility of establishing one or more
      diagnostic possibilities and guide medical management.

PMID- 22976755
TI  - [Systemic lupus erythematosus: genomics of the disease].
AB  - Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with
      multiple autoantigens as targets,resulting in damage to many organs of the body.
      The disease is more common in females (> 90%) and around 15% of the cases present
      during childhood.Systemic lupus erythematosus is a complex disease in which both
      genetic (susceptibility/protection alleles) and environmental factors
      (infections, drugs, stress, etc.) contribute to its development.The current
      knowledge on genetic factors involved in SLE is based on the results of linkage
      analyses in multi-case families as well as from case-control or family-based
      genetic association studies. These types of genetic analyses have contributed to
      identifying susceptibility genes and constitute the first step towards
      understanding the molecular mechanisms underlying SLE.The aim of this review is
      to provide a current picture of the genes identified as susceptibility factors
      for SLE, and to highlight the ones described in the Mexican population.

PMID- 22976756
TI  - [Cells of innate and adaptive immunity in type 2 diabetes and obesity].
AB  - Both type 2 diabetes mellitus (T2DM) and obesity are a major public health
      problem in Mexico and around the world for increased incidence. In T2DM, insulin
      secretion, insulin action or both are altered. Also, in T2DM as well as in
      obesity a low grade chronic inflammation has been associated. In both conditions
      there is an important increase of visceral adipose tissue, which induces to an up
      regulation of synthesis in proinflammatory molecules. This process involves
      different subsets of the immune system. The macrophages and monocytes are the
      best studied, but recently has been reported the involvement of other type of
      cells; such as neutrophils, mast cells, eosinophils, dendritic cells, NKs, NKT.
      Also, some T cells subsets, such as Th1, Th2, T regulatory, Th17 and B cells
      seems to be involved in the low grade chronic inflammation. This review focuses
      on recent evidences of the role of innate and adaptative immune system cells in
      the pathology of T2DM and obesity. We concluded with the general proposal of a
      theoretical model, how the immune cells may participate in inflammation of fat
      tissue, insulin resistance and T2DM.

PMID- 22976757
TI  - [Health in Mexico: old and rising challenges. An updated assessment].
AB  - In recent decades, Mexico has come a long way in health care matters, which has
      influenced the standard of living of the population and the development of the
      country. However, much remains to be done and changes should happen faster. Some
      of the main challenges Mexico faces currently are presented in this document and
      include: the challenge of reducing poverty in order to improve the health status
      of society; the development of health services that affect the slowdown in the
      pace of evolution of demographic indicators, life expectancy at birth and infant
      mortality; the challenge of reducing inequality; the challenge of great
      infrastructure available in the country for health care and the limited
      performance obtained in terms of organization, management and financing; the
      challenge resulting from human resources training systems, both undergraduate and
      postgraduate; the challenge that relates to academic and scientific productivity;
      the challenge of diabetes as an example of a serious public health problem; and
      the challenge of ethical implications in the organization and administration of
      health services, specifically, the allocation of public resources to them.

PMID- 22976758
TI  - [Oral erythema multiforme, an entity to be considered in the differential
      diagnosis of chronic and recurrent vesiculobullous diseases. Report of a case].
AB  - We present the case of a 23-year-old woman who was referred with an 18-month
      history, of oral ulcers finally diagnosed as erythema multiforme (EM). During
      this time she received multiple diagnoses and treatments, without resolution of
      the symptoms. The patient had a history of frequent infections by herpes simplex
      virus (HSV) in mouth, and apparently the drugs used to control it extended the
      signs and symptoms of EM. The patient showed rapid improvement after
      discontinuation of the drugs, and treatment for episodes of HSV infection was
      prescribed.

PMID- 22976759
TI  - [Some rights not constitutionally defined which are part of the rights to health.
      The Colombian case].
AB  - This paper reviews the three approaches adopted by the Colombian Constitutional
      Court to justify the protection of the right to health, and questions whether
      other rights that are not constitutionally defined, i.e. the right to a precise
      diagnosis, the right to access medical records, and the right to informed
      consent, also belong to the right to health or if they are distinctly different
      rights with a defined constitutional character.

PMID- 22976760
TI  - [The five wills of Francisco Xavier Balmis].
AB  - The recent discovery of the testamentary records of Francisco Xavier de Balmis
      (1753-1819), director of the Royal Philanthropic Expedition of the Vaccine,
      constitutes a new source material with which to study his biographical
      profile.Balmis wrote a total of five wills covering the period from 1803-1818 and
      coinciding with crucial moments in his life.The analysis of these documents has
      led to interesting observations that confirm Balmis's personal insecurity before
      facing the Expedition, his vulnerability when he was stripped of his possessions
      for joining the royalist cause against Napoleon, the reassurance he felt when his
      honors and property were restored, or his fortitude in facing the final moments
      of his life. The documents also reveal that Balmis used his career as a military
      surgeon as a tool to achieve social prestige, and belie the assumptions of an
      obscure end. The inventory of his goods confirms his comfortable economic
      situation and his ability to manage it. The notarial sources are confirmed by
      this case of Balmis, an official of the Crown, as an appropriate source for the
      study of urban oligarchies of the Spanish Ancien Regime.

PMID- 22976761
TI  - Brown-Vialetto-Van Laere and Fazio Londe syndromes: defects of riboflavin
      transport with biochemical similarities to multiple acyl-CoA dehydrogenation
      defects (MADD).

PMID- 22976762
TI  - Miglustat-induced intestinal carbohydrate malabsorption is due to the inhibition
      of alpha-glucosidases, but not beta-galactosidases.
AB  - Miglustat is an oral medication that has approved indication for type I Gaucher
      disease and Niemann pick disease type C. Usually treatment with Miglustat is
      associated with occurrence of gastrointestinal side effects similar to
      carbohydrate maldigestion symptoms. Here, we studied the direct influence of
      Miglustat on the enzymatic function of the major disaccharidases of the
      intestinal epithelium. Our findings show that an immediate effect of Miglustat is
      its interference with carbohydrate digestion in the intestinal lumen via
      reversible inhibition of disaccharidases that cleave alpha-glycosidically linked
      carbohydrates. Higher non physiological concentrations of Miglustat can partly
      affect lactase activity. We further show that the inhibition of the
      disaccharidases function by Miglustat is mainly competitive and does not occur
      via alteration of the enzyme folding.

PMID- 22976763
TI  - Non-physiological amino acid (NPAA) therapy targeting brain phenylalanine
      reduction: pilot studies in PAHENU2 mice.
AB  - Transport of large neutral amino acids (LNAA) across the blood brain barrier
      (BBB) is facilitated by the L-type amino acid transporter, LAT1. Peripheral
      accumulation of one LNAA (e.g., phenylalanine (phe) in PKU) is predicted to
      increase uptake of the offending amino acid to the detriment of others, resulting
      in disruption of brain amino acid homeostasis. We hypothesized that selected non
      physiological amino acids (NPAAs) such as DL-norleucine (NL), 2-aminonorbornane
      (NB; 2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid), 2-aminoisobutyrate (AIB),
      and N-methyl-aminoisobutyrate (MAIB), acting as competitive inhibitors of various
      brain amino acid transporters, could reduce brain phe in Pah (enu2) mice, a
      relevant murine model of PKU. Oral feeding of 5 % NL, 5 % AIB, 0.5 % NB and 3 %
      MAIB reduced brain phe by 56 % (p < 0.01), -1 % (p = NS), 27 % (p < 0.05) and 14
      % (p < 0.01), respectively, compared to untreated subjects. Significant effects
      on other LNAAs (tyrosine, methionine, branched chain amino acids) were also
      observed, however, with MAIB displaying the mildest effects. Of interest, MAIB
      represents an inhibitor of the system A (alanine) transporter that primarily
      traffics small amino acids and not LNAAs. Our studies represent the first in vivo
      use of these NPAAs in Pah (enu2) mice, and provide proof-of-principle for their
      further preclinical development, with the long-term objective of identifying NPAA
      combinations and concentrations that selectively restrict brain phe transport
      while minimally impacting other LNAAs and downstream intermediates.

PMID- 22976764
TI  - A novel congenital disorder of glycosylation type without central nervous system
      involvement caused by mutations in the phosphoglucomutase 1 gene.
AB  - Recent years have seen great advances in our knowledge of congenital disorders of
      glycosylation (CDG), a clinically and biochemically heterogeneous group of
      genetic diseases caused by defects in the synthesis (CDG-I) or processing (CDG
      II) of glycans that form glycoconjugates. This paper reports a new subtype of non
      neurological CDG involving the impaired cytoplasmic biosynthesis of nucleotide
      sugars needed for glycan biosynthesis. A patient presented with muscle fatigue,
      elevated creatine kinase, growth hormone deficiency, and first branchial arch
      syndrome. These findings, together with the abnormal type II plasma transferrin
      isoform profile detected, was compatible with a CDG. Functional testing and
      clinical analyses suggested a deficiency in the interconversion of glucose-1
      phosphate and glucose-6-phosphate catalyzed by phosphoglucomutase (PGM1), a
      defect previously described as glycogenosis type XIV (GSDXIV, MIM 612934). PGM1
      activity in patient-derived fibroblasts was significantly reduced, as was the
      quantity of immunoreactive PGM1 protein (Western blot assays). Mutation analysis
      of PGM1 and subsequent functional analysis investigating transient expression of
      PGM1 in immortalized patient fibroblasts, followed by ex vivo splicing assays
      using minigenes, allowed the characterization of two novel pathogenic mutations:
      c.871G>A (p.Gly291Arg) and c.1144 + 3A>T. The latter represents a severe splicing
      mutation leading to the out-of-frame skipping of exon 7 and the formation of a
      truncated protein (p.Arg343fs). MALDI mass spectra of permethylated protein N
      glycans from the patient's serum suggested a marked hypoglycosylation defect. The
      present findings confirm that, in addition to a rare muscular glycolytic defect,
      PGM1 deficiency causes a non-neurological disorder of glycosylation.

PMID- 22976765
TI  - Long-term clinical outcomes in type 1 Gaucher disease following 10 years of
      imiglucerase treatment.
AB  - OBJECTIVE: We studied the effect of long-term alglucerase/imiglucerase
      (Ceredase(r)/Cerezyme(r), Genzyme, a Sanofi company, Cambridge, MA, USA)
      treatment on hematological, visceral, and bone manifestations of Gaucher disease
      type 1 (GD1). METHODS: The International Collaborative Gaucher Group (ICGG)
      Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase
      who had dose and clinical data at first infusion and after 10 years of follow-up.
      Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis
      were analyzed. Tests of the null hypothesis (no change from first infusion to 10
      years) were performed using t tests for within-patient absolute change in
      continuous measurements and McNemar/chi-square tests for change in distributions
      using categorical values. An alpha level of 0.05 designated statistical
      significance. RESULTS: As of October 2011, 557 nonsplenectomized and 200
      splenectomized patients met the inclusion criteria. The majority of GD1 patients
      had at least one N370S allele. Compared with nonsplenectomized patients at first
      infusion, splenectomized patients had lower percentages of anemia (26.0 % vs.
      42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate
      or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain
      (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both
      groups showed significant (p < 0.05) improvements in mean hemoglobin levels,
      platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises.
      Initial dosing in both groups ranged from <15 U/kg to <=90 U/kg every 2 weeks.
      After 10 years, the majority was receiving 15 to <=45 U/kg every 2 weeks.
      CONCLUSION: Ten years of imiglucerase treatment results in sustainable
      improvements in all GD1 parameters.

PMID- 22976766
TI  - Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1
      under enzyme replacement therapy: a prospective study.
AB  - BACKGROUND: Dyslipidemia in Gaucher disease includes reduced total, low-density
      lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol (C). No
      prospective analysis of lipid profile changes in treatment-naive patients under
      enzyme replacement therapy (ERT) is available. METHODS: We analyzed lipid profile
      changes during ERT in a prospective controlled manner. Twelve treatment-naive
      patients, Gaucher disease type 1 (GD1), 29.5 +/- 12.9 years, 4M/8F. Diagnosis was
      made by enzymatic measurement and mutational analysis. Total-, LDL-, and HDL-C,
      triglycerides (TG), and LDL subfractions were assessed before the start of ERT
      with imiglucerase and biannually for 3 years. Patients were matched with healthy
      controls before and after 3 years of ERT. RESULTS: At baseline, we found severely
      reduced HDL-C concentrations (23.6 +/- 5.4 mg/dl) and enhanced LDL/HDL ratios
      (3.1 +/- 0.7). HDL-C increased after 6 months (29.2 +/- 5.7, p = 0.023), LDL/HDL
      ratio decreased after 30 months (2.5 +/- 0.5, p = 0.039). TG, even not
      consistently enhanced at baseline (128 +/- 31.3 mg/dl), yet higher than in
      controls (p < 0.001), decreased after 18 months, being comparable with controls
      after 3 years of ERT. Small, dense LDL (mg/dl) increased continuously without
      significant difference to controls. After 3 years of ERT, only reduced HDL-C
      concentrations persisted as a potentially atherogenic alteration; however, mean
      concentrations markedly improved (42.9 +/- 8.3 mg/dl, p < 0.001). Lipid
      parameters correlated with six markers of disease severity. CONCLUSIONS: This is
      the first prospective controlled study regarding lipid profile dynamics during
      ERT (glucocerebrosidase) in initially treatment-naive GD1 patients. The most
      important changes were reduced HDL-C and enhanced LDL/HDL ratio. Their dynamics
      during ERT and correlations with markers of disease activity suggest that they
      can be considered markers of disease severity and follow-up in Gaucher patients
      under treatment.

PMID- 22976767
TI  - Normal rates of whole-body fat oxidation and gluconeogenesis after overnight
      fasting and moderate-intensity exercise in patients with medium-chain acyl-CoA
      dehydrogenase deficiency.
AB  - BACKGROUND: Impairments in gluconeogenesis have been implicated in the
      pathophysiology of fasting hypoglycemia in medium-chain acyl-CoA dehydrogenase
      deficiency. However, whole body glucose and fat metabolism have never been
      studied in vivo. METHODS: Stable isotope methodology was applied to compare fat
      and glucose metabolism between four adult patients with MCADD and four matched
      controls both at rest and during 1.5 h of moderate-intensity exercise.
      Additionally, intramyocellular lipid and glycogen content and intramyocellular
      acylcarnitines were assessed in muscle biopsies collected prior to and
      immediately after cessation of exercise. RESULTS: At rest, plasma FFA turnover
      was significantly higher in patients with MCADD, whereas the plasma FFA
      concentrations did not differ between patients and controls. Blood glucose
      kinetics did not differ between groups both at rest and during exercise.
      Palmitate and FFA turnover, total fat and carbohydrate oxidation rates, the use
      of muscle glycogen and muscle derived triglycerides during exercise did not
      differ between patients and controls. Plasma FFA oxidation rates were
      significantly lower in patients at the latter stages of exercise. Free carnitine
      levels in muscle were lower in patients, whereas no differences were detected in
      muscle acetylcarnitine levels. CONCLUSIONS: Whole-body or skeletal muscle glucose
      and fat metabolism were not impaired in adult patients with MCADD. This implies
      that MCADD is not rate limiting for energy production under the conditions
      studied. In addition, patients with MCADD have a higher FFA turnover rate after
      overnight fasting, which may stimulate ectopic lipid deposition and, as such,
      make them more susceptible for developing insulin resistance.

PMID- 22976768
TI  - Molecular characterization of 355 mucopolysaccharidosis patients reveals 104
      novel mutations.
AB  - Mucopolysaccharidosis (MPS) disorders are heterogeneous and caused by deficient
      lysosomal degradation of glycosaminoglycans, resulting in distinct but sometimes
      overlapping phenotypes. Molecular analysis was performed for a total of 355 MPS
      patients with MPSI (n = 15), MPSII (n = 218), MPSIIIA (n = 86), MPSIIIB (n = 20),
      MPSIVA (n = 6) or MPSVI (n = 10). This analysis revealed 104 previously
      unreported mutations: seven in IDUA (MPSI), 61 in IDS (MPSII), 19 in SGSH
      (MPSIIIA), 11 in NAGLU (MPSIIIB), two in GALNS (MPSIVA) and four in ARSB (MPSVI).
      The intergenic comparison of the mutation data for these disorders has revealed
      interesting differences. Whereas IDUA, IDS, NAGLU and ARSB demonstrate similar
      levels of mutation heterogeneity (0.6-0.675 different mutations per total
      alleles), SGSH and GALNS have lower levels of mutation heterogeneity (0.282 and
      0.455, respectively), due to more recurrent mutations. The type of mutation also
      varies significantly by gene. SGSH, GALNS and ARSB mutations are usually missense
      (76.5 %, 81.8 % and 85 %), while IDUA has many more nonsense mutations (56 %)
      than the other genes (<=20%). The mutation spectrum is most diverse for IDS,
      including intergenic inversions and multi-exon deletions. By testing 102 mothers
      of MPSII patients, we determined that 22.5 % of IDS mutations are de novo. We
      report the allele frequency of common mutations for each gene in our patient
      cohort and the exonic distribution of coding sequence alterations in the IDS,
      SGSH and NAGLU genes, which reveals several potential "hot-spots". This further
      molecular characterization of these MPS disorders is expected to assist in the
      diagnosis and counseling of future patients.

PMID- 22976770
TI  - Self-reported barriers to colorectal cancer screening in a racially diverse, low
      income study population.
AB  - Colorectal cancer (CRC) screening is underutilized, especially in low income,
      high minority populations. We examined the effect test-specific barriers have on
      colonoscopy and fecal immunochemical test (FIT) completion, what rationales are
      given for non-completion, and what "switch" patterns exist when participants are
      allowed to switch from one test to another. Low income adults who were not up-to
      date with CRC screening guidelines were recruited from safety-net clinics and
      offered colonoscopy or FIT (n = 418). Follow up telephone surveys assessed test
      specific barriers. Test completion was determined from patient medical records.
      For subjects who desired colonoscopy at baseline, finding a time to come in and
      transportation applied more to non-completers than completers (p = 0.001 and p <
      0.001, respectively). For participants who initially wanted FIT, keeping track of
      cards, never putting stool on cards, and not remembering to mail cards back
      applied more to non-completers than completers (p = 0.003, p = 0.006, and p <
      0.001, respectively). The most common rationale given for not completing
      screening was a desire for the other screening modality: 7 % of patients who
      initially preferred screening by FIT completed colonoscopy, while 8 % of patients
      who initially preferred screening by colonoscopy completed FIT. We conclude that
      test-specific barriers apply more to subjects who did not complete CRC screening.
      As a common rationale for test non-completion is a desire to receive a different
      screening modality, our findings suggest screening rates could be increased by
      giving patients the opportunity to switch tests after an initial choice is made.

PMID- 22976769
TI  - Facilitation and restoration of cognitive function in primate prefrontal cortex
      by a neuroprosthesis that utilizes minicolumn-specific neural firing.
AB  - OBJECTIVE: Maintenance of cognitive control is a major concern for many human
      disease conditions; therefore, a major goal of human neuroprosthetics is to
      facilitate and/or recover the cognitive function when such circumstances impair
      appropriate decision making. APPROACH: Minicolumnar activity from the prefrontal
      cortex (PFC) was recorded from nonhuman primates trained to perform a delayed
      match to sample (DMS), via custom-designed conformal multielectrode arrays that
      provided inter-laminar recordings from neurons in the PFC layer 2/3 and layer 5.
      Such recordings were analyzed via a previously demonstrated nonlinear multi-input
      multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized
      multicolumnar firing patterns during DMS performance. MAIN RESULTS: The MIMO
      model verified that the conformal recorded individual PFC minicolumns responded
      to entrained target selections in patterns critical for successful DMS
      performance. This allowed the substitution of task-related layer 5 neuron firing
      patterns with electrical stimulation in the same recording regions during
      columnar transmission from layer 2/3 at the time of target selection. Such
      stimulation improved normal task performance, but more importantly, recovered
      performance when applied as a neuroprosthesis following the pharmacological
      disruption of decision making in the same task. SIGNIFICANCE: These findings
      provide the first successful application of neuroprosthesis in the primate brain
      designed specifically to restore or repair the disrupted cognitive function.

PMID- 22976771
TI  - A polycomponent metal-catalyzed aliphatic, allylic, and benzylic fluorination.
AB  - A group effort: Reported is the title reaction using a polycomponent catalytic
      system involving commercially available Selectfluor, a putative radical precursor
      N-hydroxyphthalimide, an anionic phase-transfer catalyst (KB(C(6)F(5))(4)), and a
      copper(I) bis(imine). The catalyst system formed leads to monofluorinated
      compounds selectively (see example) without the necessity for an excess of the
      alkane substrate.

PMID- 22976772
TI  - Heterogeneity of single small subcortical infarction can be reflected in lesion
      location.
AB  - Single small subcortical infarction (SSSI), also called lacunar infarction, has
      been regarded as a different entity with distinct pathogenesis, either
      lipohyalinosis and fibrinoid degeneration or atherosclerosis. The aim of our
      study is to identify the heterogeneity of SSSI by comparing the characteristics
      and imaging features according to lesion location. We retrospectively studied 203
      patients with acute SSSIs (diameter <=20 mm) demonstrated by diffusion-weighted
      imaging in the perforator territory of the middle cerebral artery, basilar
      artery, or vertebral artery. We divided the 203 patients according to the lesion
      location in relation to the parent artery into a distal infarction (dSSSI) group
      and a proximal infarction (pSSSI) group. We evaluated and compared the imaging
      features and clinical characteristics between the groups. The evaluated
      characteristics included indicators of lipohyalinosis [leukoaraiosis and silent
      brain infarction (SBI)], indicators of atherosclerosis [parent artery disease
      (PAD) and atherosclerosis of other cerebral arteries (AOCA)], lesion size, and
      some vascular risk factors. Between the two groups, the pSSSI group had larger
      lesion size, higher prevalence of PAD and AOCA, and greater frequency of diabetes
      mellitus, while the dSSSI group had smaller lesion size, higher prevalence of
      leukoaraiosis and SBI, and lower serum folic acid. Diversity of the SSSIs in
      imaging features and clinical characteristics according to lesion location
      suggests the heterogeneity of SSSIs; distal infarction is closely associated with
      lipohyalinosis, while proximal infarction seems to be related with
      atherosclerosis.

PMID- 22976773
TI  - Analysis of emotionality and locomotion in radio-frequency electromagnetic
      radiation exposed rats.
AB  - In the current study the modulatory role of mobile phone radio-frequency
      electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated
      in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly
      assigned into the following groups having 12 animals in each group. Group I
      (Control): they remained in the home cage throughout the experimental period.
      Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for
      28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz)
      from an active GSM (Global system for mobile communications) mobile phone with a
      peak power density of 146.60 MUW/cm(2) for 28 days. On 29th day, the animals were
      tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed
      that, percentage of entries into the open arm, percentage of time spent on the
      open arm and distance travelled on the open arm were significantly reduced in the
      RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased
      in the RF-EMR exposed rats. Defecation boli count during the EPM test was more
      with the RF-EMR group. No statistically significant difference was found in total
      distance travelled, total arm entries, percentage of closed arm entries and
      parallelism index in the RF-EMR exposed rats compared to controls. Results
      indicate that mobile phone radiation could affect the emotionality of rats
      without affecting the general locomotion.

PMID- 22976774
TI  - Larval life history and anti-predator strategies are affected by breeding
      phenology in an amphibian.
AB  - Seasonal time constraints can pose strong selection on life histories. Time
      constrained animals should prioritise fast development over predation risk to
      avoid unfavourable growing conditions. However, changes in phenology could alter
      the balance between anti-predator and developmental needs. We studied variation
      of anti-predator strategies in common frog (Rana temporaria) tadpoles in four
      populations from the two extremes of a latitudinal gradient across Sweden. We
      examined, under common conditions in the laboratory, the anti-predator responses
      and life histories of tadpoles raised with predatory Aeshna dragonfly larvae in
      two consecutive years with a difference of 20 days in breeding time in the north,
      but no difference in breeding time in the nouth. In a year with late breeding,
      northern tadpoles did not modify their behaviour and morphology in the presence
      of predators, and metamorphosed faster and smaller than tadpoles born in a year
      with early breeding. In the year with early breeding, northern tadpoles showed a
      completely different anti-predator strategy by reducing activity and developing
      morphological defences in the presence of predators. We discuss the possible
      mechanisms that could activate these responses (likely a form of environmentally
      mediated parental effect). To our knowledge, this is the first study to show that
      a vertebrate modifies the anti-predator strategy of its offspring in response to
      natural variation in reproductive phenology, which highlights the need to
      consider phenology in studies of life-history evolution.

PMID- 22976775
TI  - Social learning improves survivorship at a life-history transition.
AB  - During settlement, one of the main threats faced by individuals relates to their
      ability to detect and avoid predators. Information on predator identities can be
      gained either through direct experience or from the observation and/or
      interaction with others, a process known as social learning. In this form of
      predator recognition, less experienced individuals learn from experienced members
      within the social group, without having to directly interact with a predator. In
      this study, we examined the role of social learning in predator recognition in
      relation to the survival benefits for the damselfish, Pomacentrus wardi, during
      their settlement transition. Specifically, our experiments aimed to determine if
      P. wardi are capable of transmitting the recognition of the odour of a predator,
      Pseudochromis fuscus, to conspecifics. The experiment also examined whether there
      was a difference in the rate of survival between individuals that directly learnt
      the predator odour and those which acquired the information through social
      learning compared to naive individuals. Results show that naive P. wardi are able
      to learn a predator's identity from experienced individuals via social learning.
      Furthermore, survival between individuals that directly learnt the predator's
      identity and those that learnt through social learning did not significantly
      differ, with fish from both treatments surviving at least five times better than
      controls. These results demonstrate that experience may play a vital role in
      determining the outcome of predator-prey interactions, highlighting that social
      learning improves the ability of prey to avoid and/or escape predation at a life
      history transition.

PMID- 22976776
TI  - Monozygotic twins with LRRK2 mutations: genetically identical but phenotypically
      discordant.

PMID- 22976777
TI  - Whipple's disease presenting with segmental myoclonus and hypersomnia.

PMID- 22976778
TI  - Nigrostriatal pathway dysfunction in a methanol-induced delayed dystonia
      parkinsonism.

PMID- 22976779
TI  - Single fluorescent probe displays a distinct response to Zn2+ and Cd2+.
AB  - Single probe, multiple targets: the design and synthesis of a new probe is
      described that can readily discriminate Zn(2+) and Cd(2+) with different
      fluorescence signals. The studies of Job's plot, mass spectroscopy, DFT
      calculations, and (1)H NMR spectroscopy reveal that the new probe has possible
      distinct binding modes to Zn(2+) and Cd(2+). This work may open up new
      opportunities for the development of single fluorescent probes that can sense
      multiple targets of interest.

PMID- 22976780
TI  - Overview of electronic data sharing: why, how, and impact.
AB  - Electronic data sharing is a critical, but underappreciated, requirement for
      modern medical informatics systems. This capability is facilitated by acquisition
      of structured clinical data, but optimized only if this data is stored and
      transmitted using standardized representations. Most electronic medical record
      and clinical trials management systems are poorly suited for data sharing. In the
      near future, sharing clinical outcome data is likely to become very important, so
      these capabilities must be improved. In this article, basic concepts of
      electronic data sharing are reviewed and their use illustrated in a data-sharing
      project developed to support Hematopoietic Cell Transplantation reporting to a
      national database.

PMID- 22976781
TI  - Epigallocatechin gallate affects survival and metabolism of human sperm.
AB  - SCOPE: Green tea and its major constituent epigallocatechin gallate (EGCG) have
      been extensively studied as potential treatment for a variety of diseases. We
      assessed the influence of EGCG on male fertilizing potential by analyzing
      different features of human sperm involved in capacitation process. METHODS AND
      RESULTS: Using human normozoospermic samples, we evaluated the effect of EGCG (2
      MUM, 20 MUM, 60 MUM) on sperm activities. Our results showed that lower doses of
      EGCG (from 2 to 20 MUM) increased cholesterol efflux and tyrosine phosphorylation
      through the estrogen receptor (ER), since ICI 182,780, a specific ER antagonist,
      abrogated 20 MUM EGCG effects. Besides, we evidenced that EGCG at similar
      concentrations, increased sperm motility, viability, and phosphorylation of
      proteins controlling cell survival such as Bcl2, Akt, and Src, via ER.
      Furthermore, we observed reduction of triglycerides content, induction of lipase,
      as well as the G6PDH activity. These results address to an increase in energy
      expenditure. On the contrary, treatment of 60 MUM EGCG produced opposite effects
      that still appear after ICI cotreatment. CONCLUSION: These results provide a
      novel mechanism involving ERs through which low doses of EGCG exerted benefits to
      sperm physiology, also detected data evidence the adverse action of high EGCG
      concentrations probably related to its prooxidant and antiestrogenic potential.

PMID- 22976782
TI  - Locally delivered 0.5% clarithromycin, as an adjunct to nonsurgical treatment in
      chronic periodontitis with well-controlled type 2 diabetes: a randomized
      controlled clinical trial.
AB  - OBJECTIVE: Several epidemiologic studies have identified a greater incidence of
      periodontitis in patients with type 2 diabetes. Recent developments suggest that
      local delivery of antimicrobials into periodontal pockets improve periodontal
      health. The present study was designed to investigate the adjunctive effects of
      subgingivally delivered clarithromycin (CLM) (0.5% concentration) as an adjunct
      to scaling and root planing for treating chronic periodontitis in patients with
      well-controlled type 2 diabetes. METHODS: Sixty-three patients were categorized
      into two treatment groups: Group 1, scaling and root planing (SRP) plus 0.5% CLM;
      Group 2, SRP plus placebo gel. Clinical parameters were recorded at baseline, 1,
      2, and 3 months; which included gingival index (GI), sulcus bleeding index (SBI),
      plaque index (PI), probing depth (PD), and periodontal attachment level (PAL).
      RESULTS: Both therapies resulted in significant improvements. Using a subject
      based analysis, patients in Group 1 treated with SRP + CLM showed enhanced
      reductions in PI, GI, SBI, and PD, and gains in PAL (P < 0.001) over a period of
      6 months as compared to Group 2. CONCLUSION: Although both treatment strategies
      seemed to benefit the patients, the adjunctive use of 0.5% CLM as a controlled
      drug delivery system enhanced the clinical outcome.

PMID- 22976783
TI  - Yb(NTf2)3-catalyzed [3 + 3] cycloaddition between isatin ketonitrones and
      cyclopropanes to construct novel spiro[tetrahydro-1,2-oxazine]oxindoles.
AB  - Yb(NTf(2))(3)-catalyzed [3 + 3] cycloaddition between isatin ketonitrones and
      cyclopropanes is described. A variety of spiro[tetrahydro-1,2-oxazine]oxindoles
      were obtained in moderate to good yields along with good regioselectivities. This
      is the first example of the intermolecular [3 + 3] cycloaddition between ketone
      derived nitrones and cyclopropanes.

PMID- 22976785
TI  - The role of residues T248, Y249 and T422 in the function of human pregnane X
      receptor.
AB  - The pregnane X receptor (PXR) is a key xenobiotic receptor that regulates the
      expression of numerous drug-metabolizing enzymes. Some posttranslational
      mechanisms modulate its transcriptional activity. Although several kinases have
      been shown to directly phosphorylate this receptor, little is known about
      phosphorylation sites of PXR. In the present work, we examined T248, Y249 and
      T422 putative phosphorylation sites determined based on in silico consensus
      kinase site prediction analysis. T248 and T422 residues are critical for the
      interaction of the PXR ligand-binding domain and the activation function-2 (AF2)
      domain. Site-directed mutagenesis analysis was performed to generate phospho
      deficient and phospho-mimetic mutants. We examined transactivation activity of
      the PXR mutants in gene reporter assays, formation of PXRmutant/RXRalpha
      heterodimer, binding of PXR mutants to the CYP3A4 gene response element DR3 and
      CYP3A4 expression in HepG2 cells after expression of the mutants. We found that
      T248D mutant activated CYP3A4 transactivation constitutively regardless of the
      presence or absence of a ligand. Contrary, T248V mutant exhibited low basal and
      ligand-inducible transactivation capacity as compared to wild-type PXR. Dose
      response analysis revealed reduced ligand-dependent transactivation potency of
      PXR Y249D mutant. Transactivation of the CYP3A4 promoter was abolished with
      T422A/D mutants. All PXR mutants formed heterodimer with RXRalpha at a similar
      level to that observed with wild-type PXR. The ability to bind to DNA in vitro
      was substantially decreased in case of T248D, T422D and T248V mutants. Our data
      thus indicate that phosphorylation of T248, Y249 and T422 residues may be
      critical for the both basal and ligand-activated function of PXR.

PMID- 22976787
TI  - Investigations of the marine flora and fauna of the Fiji Islands.
AB  - Over the past 30 years, approximately 140 papers have been published on marine
      natural products chemistry and related research from the Fiji Islands. These came
      about from studies starting in the early 1980s by the research groups of Crews at
      the University of California Santa Cruz, Ireland at the University of Utah,
      Gerwick from the Scripps Institution of Oceanography, the University of
      California at San Diego and the more recent groups of Hay at the Georgia
      Institute of Technology (GIT) and Jaspars from the University of Aberdeen. This
      review covers both known and novel marine-derived natural products and their
      biological activities. The marine organisms reviewed include invertebrates,
      plants and microorganisms, highlighting the vast structural diversity of
      compounds isolated from these organisms. Increasingly during this period, natural
      products chemists at the University of the South Pacific have been partners in
      this research, leading in 2006 to the development of a Centre for Drug Discovery
      and Conservation (CDDC).

PMID- 22976788
TI  - Response to subspecialty training in preventive cardiology: the current status
      and discoverable fellowship programs.

PMID- 22976789
TI  - Is there a role for carboplatin in the treatment of malignant germ cell tumors? A
      systematic review of adult and pediatric trials.
AB  - BACKGROUND: While cisplatin is considered superior to carboplatin for the
      treatment of malignant germ cell tumors (MGCTs) in adults, pediatric oncology
      collaborative groups still remain concerned about the late effects of cisplatin
      in children. METHODS: We performed a literature search to identify randomized
      controlled trials (RCTs) that used carboplatin for MGCTs in adults. Since no RCTs
      were available in children, we identified cohort studies of pediatric MGCTs
      treated with carboplatin. We compared the adult and pediatric studies in terms of
      characteristics, doses of chemotherapy, and outcomes. RESULTS: Of 2,131
      publications retrieved, five RCTs in adults (1,340 patients) and four cohort
      studies in children (219 patients) met criteria for inclusion. All adult RCTs
      evaluated carboplatin versus cisplatin regimens in men with good-prognosis
      metastatic MGCTs. Carboplatin regimens had a higher risk of events (RR 2.51, P <
      0.001) and of deaths (RR 2.21, P < 0.001) than cisplatin regimens. Across all
      five RCTs, 497/654 (76%) of adults who received carboplatin remained event-free.
      Compared to the adult trials, three pediatric studies used carboplatin at a
      higher dose, frequency, and number of cycles. Across these three studies, 158/179
      (88%) of children remained event-free. CONCLUSIONS: Cisplatin is superior to
      carboplatin at the studied doses for the treatment of adult metastatic MGCTs.
      However, we observe that carboplatin is associated with good outcomes for
      children with MGCT when used at the higher doses. We hypothesize that a risk
      adapted approach utilizing both platinum agents may achieve the optimal balance
      between cure and late effects.

PMID- 22976790
TI  - Do hernia operations in african international cooperation programmes provide good
      quality?
AB  - BACKGROUND: Hernia is especially prevalent in developing countries where the
      population is obliged to undertake strenuous work in order to survive, and
      International Cooperation Programmes are helping to solve this problem. However,
      the quality of surgical interventions is unknown. The objective of the present
      study was to evaluate the quality of hernia repair processes carried out by the
      Surgical Solidarity Charity in Central African States. MATERIALS AND METHODS: A
      total of 524 cases of inguinal hernia repair carried out in Cameroon and Mali
      during 2005 to 2009 were compared with 386 cases treated in a Multicentre Spanish
      Study (2003). General data (clinical, demographic, etc.), type of surgery,
      complications, and effectiveness and efficiency indicators were collected.
      RESULTS: Preoperative studies in the Spanish group were greater in number than in
      the African group. The use of local anesthesia was similar. Antibiotic
      prophylaxis was higher in the African group (100% to 75.4%). The use of mesh was
      similar. The incidence of hematomas was higher in the Spanish group (11.61% to
      4.61%), but the incidence of infection of the wound and of hernia recurrence was
      similar, although follow-up was only carried out in 20.97% in the African group
      (70% in the Spanish group). Hospital stay of more than 24 h was higher in the
      Spanish group. CONCLUSIONS: The standard quality of surgery for the treatment of
      hernia in developing countries with few instrumental means, and in sub-optimal
      surgical conditions is similar to that provided in Spain.

PMID- 22976791
TI  - Relationship between preoperative volume and weight of the right liver lobe
      graft, with and without the middle hepatic vein, in living-donor transplantation.
AB  - BACKGROUND: The aim of this study was to assess the relationship between the
      preoperative volume of the right liver lobe (as determined by computed
      tomography) and the intraoperative graft weight with or without the middle
      hepatic vein. METHODS: Sixty-three patients who underwent liver transplantation
      were included in this study. The preoperative volumes of both the left and the
      right liver lobe were measured in all patients using computed tomography. The
      intraoperative weight of the right liver lobe was also measured with (group 1, n
      = 29) and without (group 2, n = 34) the middle hepatic vein. The results were
      compared with respect to gender, age, body weight, height, body mass index (BMI),
      weights of the left and right liver lobes as measured by computed tomography, and
      intraoperative weight of the right liver lobe. RESULTS: A 21.64 % difference was
      observed between the weight of the right liver lobe as measured by computed
      tomography and the weight of the right lobe without the hepatic vein as measured
      intraoperatively (group 2). Moreover, a 12.38 % difference was observed between
      the weight of the right liver lobe as measured by computed tomography and the
      weight of the right lobe plus the middle hepatic vein as measured
      intraoperatively (group 1). CONCLUSIONS: The weight of the right liver lobe graft
      in a living-donor transplantation is less than that calculated by preoperative
      computed tomography, and the inclusion of the middle hepatic vein in the right
      liver lobe graft resulted in a statistically significant decrease in this
      difference.

PMID- 22976792
TI  - Cost-comparison of laparoscopic and open surgery for mid or low rectal cancer
      after preoperative chemoradiotherapy: data from a randomized controlled trial.
AB  - BACKGROUND: The purpose of the present study was to compare the direct costs of
      laparoscopic surgery (LS) and open surgery (OS) in the treatment of mid or low
      rectal cancer after preoperative chemoradiotherapy in patients in Korea. METHODS
      AND RESULTS: The records of 130 LS patients and 125 OS patients were reviewed.
      Hospital stay after surgery and overall complication rates within three months of
      surgery were not significantly different. The LS group had significantly higher
      median costs than the OS group ($7,467.30 vs. $5,667.00; P < 0.001). The median
      hospital costs during hospitalization for surgery were higher in the LS group
      ($7,436.60 vs. $5,626.60; P < 0.001), but hospital costs for management of early
      postoperative complications were similar. The higher direct costs of LS were
      mainly due to the more expensive consumables and equipment needed for LS.
      CONCLUSIONS: Further study is needed to determine whether the higher direct costs
      of LS for rectal cancer are balanced by advantages of LS over OS, such as better
      short-term outcomes and cosmetic effect.

PMID- 22976793
TI  - Clinical assessment of axillary lymph nodes and tumor size in breast cancer
      compared with histopathological examination: a population-based analysis of 2,537
      women.
AB  - BACKGROUND: The clinical assessment of axillary lymph nodes status and tumor size
      is important for the management of patients with breast cancer. The first goal of
      this study was to determine the accuracy of axillary lymph node status in
      relation to the presence of metastases as revealed by histopathological
      examination. The second goal was to compare the tumor size as assessed by
      physical examination, with the size obtained by histopathological examination.
      METHODS: This study was based on a consecutive series of 2,537 patients diagnosed
      with breast cancer in Malmo, Sweden, between 1987 and 2002. These patients had
      available information in the South Swedish Breast Cancer Group registry,
      corresponding to 97 %. The axillary lymph nodes status was compared with the
      results of the histopathological examination for the presence of metastases.
      Tumor size by physical examination was compared with the tumor size after
      histopathological examination. RESULTS: There were 674 women with axillary lymph
      nodes metastases according to histological examination; only 206 of these cases
      had palpable lymph nodes at clinical examination. The sensitivity was 30 % and
      the specificity 93 %. There were 812 tumors measured to be larger than 20 mm
      according to histopathological examination, but only 665 of these tumors were
      considered larger than 20 mm by clinical examination. This corresponded to a
      sensitivity of 81 % and a specificity of 80 %. CONCLUSIONS: We conclude that the
      possibility of axillary metastases estimated by clinical examination is subjected
      to a large proportion of false-positive and false-negative results. Similarly,
      tumor size estimated by clinical examination is subject to under- and
      overestimation in comparison to histopathological examination.

PMID- 22976794
TI  - Effects of post-migration factors on PTSD outcomes among immigrant survivors of
      political violence.
AB  - This study examined the predictors of posttraumatic stress disorder (PTSD) in a
      clinical sample of 875 immigrant survivors of political violence resettled in the
      United States, with a specific aim of comparing the relative predictive power of
      pre-migration and post-migration experiences. Results from a hierarchical OLS
      regression indicated that pre-migration experiences such as rape/sexual assault
      were significantly associated with worse PTSD outcomes, as were post-migration
      factors such as measures of financial and legal insecurity. Post-migration
      variables, which included immigration status in the US, explained significantly
      more variance in PTSD outcomes than premigration variables alone. Discussion
      focused on the importance of looking at postmigration living conditions when
      treating trauma in this population. 

PMID- 22976795
TI  - Occupational health outcomes among self-identified immigrant workers living and
      working in Somerville, Massachusetts 2006-2009.
AB  - This study examines the burden of occupational health risks among a convenience
      sample of three immigrant worker populations (Brazilian, Haitian, and El
      Salvadoran) in Somerville, Massachusetts. In this community based research
      initiative (n = 346), logistic regression is used to analyze immigrant
      occupational health survey data collected from 2006 to 2009. In this study,
      injuries at work were significantly associated with lower English proficiency (OR
      = 1.8, 95 % CI 1.1-3.0), workers between the ages of 46 and 65 (OR = 2.7, 95 % CI
      1.0-7.0), service workers (OR = 13.8, 95 % CI 1.8-105.2), production workers (OR
      = 10.8, 95 % CI 1.3-90.1), construction workers (OR: 21.7, 95 % CI 2.8-170.9) and
      immigrants with no health insurance (OR = 1.8, 95 % CI 1.0-3.1). Injuries were
      negatively associated with years in the US with more established immigrants in
      the US >15 years reporting more injuries at work. Older immigrants who have been
      in the US longer but are less proficient in English, and are still employed in
      low-wage occupations with no health insurance suffered more injuries than recent
      immigrants. Further validation of this result is required.

PMID- 22976796
TI  - Trauma, healthcare access, and health outcomes among Southeast Asian refugees in
      Connecticut.
AB  - Mental health problems among Southeast Asian refugees have been documented.
      However, longer term health consequences of mass violence as re-settled refugees
      age are less well described. This study investigated relationships among trauma
      symptoms, self-reported health outcomes, and barriers to healthcare among
      Cambodian and Vietnamese persons in Connecticut. An internet phone directory was
      used to generate a list of names that was compared to 2000 census data to
      estimate the proportion of the population in each group. From these lists, 190
      telephone listings were selected at random. Interviewers telephoned selected
      listings to screen for eligible participants and obtain an appointment for
      interview. Surveys were administered through face-to-face interviews during home
      visits conducted in Khmer or Vietnamese. The Harvard Trauma Questionnaire
      assessed trauma symptoms. Questions regarding the presence of physician diagnosed
      heart disease, hypertension, diabetes, and chronic pain were adapted as written
      from the Health Interview Survey. Healthcare access and occurrence were measured
      with questions regarding cost and access, patient-provider understanding, and
      interpretive services. Hierarchical modeling was used to account for respondent
      nesting within family. Analyses controlled for age, sex, and country of origin.
      Individuals who reported greater trauma symptoms were more likely to report heart
      disease by a factor of 1.82, hypertension by a factor of 1.41, and total count of
      diseases by a factor of 1.22, as well as lower levels of subjective health.
      Greater trauma symptoms were also associated with greater lack of understanding,
      cost and access problems, and the need for an interpreter. Although the majority
      of Southeast Asian immigrants came to the United States as refugees approximately
      20-30 years ago, there continues to be high levels of trauma symptoms among this
      population which are associated with increased risk for disease and decreased
      access to healthcare services. 

PMID- 22976797
TI  - Notch-mediated induction of N-cadherin and alpha9-integrin confers higher
      invasive phenotype on rhabdomyosarcoma cells.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma
      in children. Patients with metastatic RMS continue to have very poor prognosis.
      Recently, several works have demonstrated a connection between Notch pathway
      activation and the regulation of cell motility and invasiveness. However, the
      molecular mechanisms of this possible relationship remain unclear. METHODS: The
      Notch pathway was manipulated pharmacologically and genetically. The mRNA changes
      were analysed by quantitative PCR and protein variations by western blot and
      immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a
      wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)-
      and alpha9-integrin-blocking antibodies. RESULTS: Cells treated with gamma
      secretase inhibitor showed lower adhesion capability and downregulation of N
      cadherin and alpha9-integrin. Genetic manipulation of the Notch pathway led to
      concomitant variations in N-cadherin and alpha9-integrin. Treatment with anti-N
      cadherin-blocking antibody rendered marked inhibition of cell adhesion and
      motility, while anti-alpha9-integrin-blocking antibody exerted a remarkable
      effect on cell adhesion and invasiveness. CONCLUSION: Neuronal cadherin and
      alpha9-integrin are postulated as leading actors in the association between the
      Notch pathway and promotion of cell adhesion, motility and invasion, pointing to
      these proteins and the Notch pathway itself as interesting putative targets for
      new molecular therapies against metastases in RMS.

PMID- 22976798
TI  - Analysis of molecular intra-patient variation and delineation of a prognostic 12
      gene signature in non-muscle invasive bladder cancer; technology transfer from
      microarrays to PCR.
AB  - BACKGROUND: Multiple clinical risk factors and genetic profiles have been
      demonstrated to predict progression of non-muscle invasive bladder cancer;
      however, no easily clinical applicable gene signature has been developed to
      predict disease progression independent of disease stage and grade. METHODS: We
      measured the intra-patient variation of an 88-gene progression signature using 39
      metachronous tumours from 17 patients. For delineation of the optimal
      quantitative reverse transcriptase PCR panel of markers, we used 115 tumour
      samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of
      intra-patient variation of the molecular markers showed 71% similar
      classification results. A final panel of 12 genes was selected, showing
      significant correlation with outcome. In multivariate Cox regression analysis, we
      found that the 12-gene signature was an independent prognostic factor (hazard
      ratio=7.4 (95% confidence interval: 3.4-15.9), P<0.001) when adjusting for stage,
      grade and treatment. Independent validation of the 12-gene panel and the
      determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker
      variation in metachronous tumours is present. Therefore, to increase test
      sensitivity, it may be necessary to test several metachronous tumours from a
      patient's disease course. A PCR-based 12-gene signature significantly predicts
      disease progression in patients with non-muscle invasive bladder cancer.

PMID- 22976799
TI  - Gut microbiota-derived propionate reduces cancer cell proliferation in the liver.
AB  - BACKGROUND: Metabolites released by the gut microbiota may influence host
      metabolism and immunity. We have tested the hypothesis that inulin-type fructans
      (ITF), by promoting microbial production of short-chain fatty acids (SCFA),
      influence cancer cell proliferation outside the gut. METHODS: Mice transplanted
      with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut
      microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)-denaturing
      gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were
      quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular
      biology and histology, and in vitro. RESULTS: Inulin-type fructans treatment
      reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal
      propionate concentration. In vitro, propionate reduces BaF3 cell growth through a
      cAMP level-dependent pathway. Furthermore, the activation of free fatty acid
      receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that
      binds propionate, lessens the proliferation of BaF3 and other human cancer cell
      lines. CONCLUSION: We show for the first time that the fermentation of nutrients
      such as ITF into propionate can counteract malignant cell proliferation in the
      liver tissue. Our results support the interest of FFA2 activation as a new
      strategy for cancer therapeutics. This study highlights the importance of
      research focusing on gut microbes-host interactions for managing systemic and
      severe diseases such as leukaemia.

PMID- 22976800
TI  - Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma
      cell lines that is uncommon in primary medulloblastoma tumours.
AB  - BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in
      O(6)-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR)
      proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was
      analysed with clonogenic survival assays. Expression of DNA repair genes and
      enzymes was investigated using microarrays, western blot, and
      immunohistochemistry. DNA sequencing and promoter methylation analysis were
      employed to investigate the cause of loss of the expression of MMR gene MLH1.
      RESULTS: Temozolomide exhibited potent cytotoxic activity in D425Med (MGMT
      deficient, MLH1 proficient; IC(50)=1.7 MUM), moderate activity against D341Med
      (MGMT proficient, MLH1 deficient), and DAOY MB cells (MGMT proficient, MLH1
      proficient). MGMT inhibitor O(6)-benzylguanine sensitised DAOY, but not D341Med
      cells to TMZ. Of 12 MB cell lines, D341Med, D283Med, and 1580WU cells exhibited
      MMR deficiency due to MLH1 promoter hypermethylation. DNA sequencing of these
      cells provided no evidence for somatic genetic alterations in MLH1. Expression
      analyses of MMR and MGMT in MB revealed that all patient specimens (n=74;
      expression array, n=61; immunostaining, n=13) are most likely MMR proficient,
      whereas some tumours had low MGMT expression levels (according to expression
      array) or were totally MGMT deficient (3 out of 13 according to
      immunohistochemistry). CONCLUSION: A subset of MB may respond to TMZ as some
      patient specimens are MGMT deficient, and tumours appear to be MMR proficient.

PMID- 22976801
TI  - Segmental chromosomal alterations have prognostic impact in neuroblastoma: a
      report from the INRG project.
AB  - BACKGROUND: In the INRG dataset, the hypothesis that any segmental chromosomal
      alteration might be of prognostic impact in neuroblastoma without MYCN
      amplification (MNA) was tested. METHODS: The presence of any segmental
      chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome
      17q gain) defined a segmental genomic profile. Only tumours with a confirmed
      unaltered status for all three chromosome arms were considered as having no
      segmental chromosomal alterations. RESULTS: Among the 8800 patients in the INRG
      database, a genomic type could be attributed for 505 patients without MNA: 397
      cases had a segmental genomic type, whereas 108 cases had an absence of any
      segmental alteration. A segmental genomic type was more frequent in patients >18
      months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion,
      17q gain and a segmental genomic type were associated with a poorer event-free
      survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate
      analysis modelling EFS, the parameters age, stage and a segmental genomic type
      were retained in the model, whereas the individual genetic markers were not
      (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively).
      CONCLUSION: A segmental genomic profile, rather than the single genetic markers,
      adds prognostic information to the clinical markers age and stage in
      neuroblastoma patients without MNA, underlining the importance of pangenomic
      studies.

PMID- 22976802
TI  - Examining dietary variability of the earliest farmers of south-eastern Italy.
AB  - Stable isotope analysis of human remains has been used to address long-standing
      debates regarding the speed and degree to which the introduction of farming
      transformed diet. In Europe, this debate has centered on northern and Atlantic
      regions with much less attention devoted to the arrival of farming across the
      Mediterranean. This study presents carbon and nitrogen stable isotope analyses of
      collagen from 19 human and 37 faunal remains from eight sites in the Apulia and
      Marche regions of south-eastern and central Italy, dating to the early phases of
      agricultural adoption during the first half of the 6th Millennium BC. Where
      collagen preservation permitted, sulfur stable isotope analysis was also
      performed. Overall, there was significant isotopic variation between the
      different geographic regions, although there was also considerable uncertainty in
      interpreting these data, especially given heterogeneous isotope values for fauna
      from site to site. By considering isotope data from each region separately, it
      was noticeable that the degree of carbon isotope enrichment in humans compared to
      fauna was higher for individuals buried near the coast, consistent with increased
      marine consumption. Coastal individuals also had higher sulfur isotope values.
      Nitrogen isotope values were very variable between individuals and regions and,
      in some cases, were consistent with very high plant food consumption. Overall,
      early "farmers" in south-east and central Italy consumed a wide range of foods,
      including marine, and had much more variable stable isotope values than those
      observed in central and northern Europe during this period, perhaps indicating a
      different mode for agricultural adoption.

PMID- 22976803
TI  - Structural evolution of single-layer films during deposition of silicon on
      silver: a first-principles study.
AB  - In the quest for the construction of silicene, the silicon analogue of  graphene,
      recent experimental studies have identified a number of distinct ultrathin Si
      over-layer structures on a Ag(111) surface. Here we use first-principles
      calculations to probe associated atomic-scale mechanisms that can give rise to
      this rich behavior of Si wetting layers. We find that the interaction between the
      Si film and the Ag substrate, neither too strong nor too weak, combined with the
      possibility of buckling, allows for the incorporation of a number of excess Si
      adatoms in continuous overlayers with a honeycomb network topology. Depending on
      the Si coverage, we thus obtain a hierarchy of Si mono-atomic films, in agreement
      with experiments.

PMID- 22976804
TI  - Deep sequencing reveals small RNA characterization of invasive micropapillary
      carcinomas of the breast.
AB  - Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of
      breast cancer. IMPC has a special growth pattern and a more aggressive behavior
      than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a
      large class of non-coding RNAs involved in the regulation of various biological
      processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed
      paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by
      means of next-generation sequencing, generating a total of >170,000,000 clean
      reads. In an unsupervised cluster analysis, differently expressed miRNAs
      generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired
      fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By
      means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22)
      and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a,
      miR-181a*, and miR-181b were significantly differently expressed between the two
      groups. We also elucidated several features of miRNA in these breast cancer
      tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our
      findings will lead to further understanding of the invasive potency of IMPC and
      gain an insight into the diversity and complexity of small RNA molecules in
      breast cancer tissues.

PMID- 22976805
TI  - GSK3beta and cyclin D1 expression predicts outcome in early breast cancer
      patients.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is phosphorylated and inactivated by
      the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates
      GSK3beta preventing phosphorylation of cyclin D1 which leads to accumulation and
      nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle
      progression. The CCND1 gene found at chromosome 11q13 has been shown to be
      amplified in approximately 15 % of breast cancers. Cyclin D1, the product of the
      CCND1 gene, is one of the most commonly overexpressed proteins in breast cancer.
      Protein expression for GSK3beta, phosphorylated-GSK3beta (p-GSK3beta), cyclin D1
      and gene expression of CCND1 were examined in tissue microarrays of 1,686
      patients from the Edinburgh Breast Conservation Series. High GSK3beta expression
      was associated with reduced distant relapse-free survival (DRFS), while no
      association between p-GSK3beta and breast cancer-specific survival was seen.
      CCND1 amplification is also associated with poor DRFS. On the contrary, cyclin D1
      overexpression is associated with an increase in DRFS. Multivariate analysis was
      performed. We suggest that analysis of both GSK3beta and cyclin D1 expressions
      can be considered as a marker of good prognosis in early breast cancer.

PMID- 22976806
TI  - Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and
      pathway activity in triple negative breast cancer.
AB  - The purpose of this study is to explore the relationship between tumor hypoxia
      assessed by CA IX protein expression and loss of BRCA1 function in triple
      negative breast cancer (TNBC). Protein expression of CA IX and BRCA1 was
      evaluated by AQUATM technology on two breast cancer cohorts: an unselected cohort
      of 637 breast cancer patients and a TNBC cohort of 120 patients. Transcriptional
      profiling was performed on FFPE samples from the TNBC cohort to evaluate a gene
      expression signature associated with BRCA1 mutation (van't Veer et al., Nature
      415(6871):530-536, 2002). CA IX is expressed in 7 % of the unselected breast
      cancer cohort and in 25 % of the TNBCs and is significantly associated with the
      triple negative phenotype. CA IX protein expression and BRCA1 protein expression
      are inversely correlated in both cohorts. Patients expressing high levels of CA
      IX show significantly worse overall survival (p = 0.02). Importantly, high CA IX
      protein expression occurs in patients who show the BRCA1 mutant signature and low
      levels of BRCA1 protein. These data suggest that elevated CA IX protein in TNBC
      is associated with a BRCA1 mutant signature and loss of BRCA1 function. CA IX may
      be a useful biomarker to identify triple negative patients with defective
      homologous recombination, who might benefit from PARP inhibitor therapy.

PMID- 22976807
TI  - Role of ornithine decarboxylase in regulation of estrogen receptor alpha
      expression and growth in human breast cancer cells.
AB  - Our previous studies demonstrated that specific polyamine analogues, oligoamines,
      down-regulated the activity of a  key polyamine biosynthesis enzyme, ornithine
      decarboxylase (ODC), and suppressed expression of estrogen receptor alpha
      (ERalpha) in human breast cancer cells. However, the mechanism underlying the
      potential regulation of ERalpha expression by polyamine metabolism has not been
      explored. Here, we demonstrated that RNAi-mediated knockdown of ODC (ODC KD) down
      regulated the  polyamine pool, and hindered growth in ERalpha-positive MCF7 and
      T47D and ERalpha-negative MDA-MB-231 breast cancer cells. ODC KD significantly
      induced the expression and activity of the key polyamine catabolism enzymes,
      spermine oxidase (SMO) and spermidine/spermine N (1)-acetyltransferase (SSAT).
      However, ODC KD-induced growth inhibition could not be reversed by exogenous
      spermidine or overexpression of antizyme inhibitor (AZI), suggesting that
      regulation of ODC on cell proliferation may involve the signaling pathways
      independent of polyamine metabolism. In MCF7 and T47D cells, ODC KD, but not DFMO
      treatment, diminished the mRNA and protein expression of ERalpha. Overexpression
      of antizyme (AZ), an ODC inhibitory protein, suppressed ERalpha expression,
      suggesting that ODC plays an important role in regulation of ERalpha expression.
      Decrease of ERalpha expression by ODC siRNA altered the mRNA expression of a
      subset of ERalpha response genes. Our previous analysis showed that oligoamines
      disrupt the binding of Sp1 family members to an ERalpha minimal promoter element
      containing GC/CA-rich boxes. By using DNA affinity precipitation and mass
      spectrometry analysis, we identified ZBTB7A, MeCP2, PARP-1, AP2, and MAZ as co
      factors of Sp1 family members that are associated with the ERalpha minimal
      promoter element. Taken together, these data provide insight into a novel
      antiestrogenic mechanism for polyamine biosynthesis enzymes in breast cancer.

PMID- 22976808
TI  - A cell-based approach to the human proteome project.
AB  - The general scope of a project to determine the protein molecules that comprise
      the cells within the human body is framed. By focusing on protein primary
      structure as expressed in specific cell types, this concept for a cell-based
      version of the Human Proteome Project (CB-HPP) is crafted in a manner analogous
      to the Human Genome Project while recognizing that cells provide a primary
      context in which to define a proteome. Several activities flow from this
      articulation of the HPP, which enables the definition of clear milestones and
      deliverables. The CB-HPP highlights major gaps in our knowledge regarding cell
      heterogeneity and protein isoforms, and calls for development of technology that
      is capable of defining all human cell types and their proteomes. The main
      activities will involve mapping and sorting cell types combined with the
      application of beyond the state-of-the art in protein mass spectrometry.

PMID- 22976809
TI  - Dissecting the influence of oxazolidinones and cyclic carbonates in sialic acid
      chemistry.
AB  - At a moment's notice: Thermal equilibration of 1 and mass spectral analysis of
      sialyl phosphates suggest that the 4O,5N-oxazolidinone and the 4,5-O-carbonate
      systems influence the anomeric effect and the mechanisms of sialidation by virtue
      of their dipole moment in the mean plane of the pyranose ring. The electron
      withdrawing effect destabilizes 2 and promotes associative glycosylation
      mechanisms. TEMPO = 2,2,6,6-tetramethylpiperidine N-oxide.

PMID- 22976810
TI  - The effect of either topical menthol or a placebo on functioning and knee pain
      among patients with knee OA.
AB  - Osteoarthritis (OA) is a common health problem with symptoms including reduced
      functioning and joint pain. Protracted pharmacological management of knee OA is
      associated with side effects including gastrointestinal, renal, and neurological
      dysfunction. Menthol gels have been used with limited empirical support to
      relieve pain and improve functioning among individual with OA. The purpose of
      this study was to compare the ability to complete functional tasks and knee pain
      while completing functional tasks among patients with knee OA after topical
      application of either 3.5% menthol gel or an inert placebo gel. Twenty
      individuals with knee OA volunteered to complete 2 data collection visits 1 week
      apart. Subjects underwent the same data collection at each visit including the
      performance of functional tasks and self-reporting knee pain while performing
      each task. The functional tasks included a 6-Minute Walk (6-MW), the Timed Get Up
      and Go (TUG), 30-second timed chair stand (TCS), and time to ascend (Up stairs)
      and descend (Down stairs) a flight of stairs. Subjects reported their knee pain
      immediately following each functional task using a 100-mm visual analog scale.
      These assessments of pain and functioning were measured twice at each subject
      visit: upon arrival at the facility without any intervention and again during the
      same visit after random application to the OA knee of 5 mL of 3.5% menthol gel or
      5 mL of an inert gel. There were no significant between-group differences or time
      by treatment interaction in performance of any of the functional tasks, or
      measures of pain, at any of the data collection time points. However, there were
      significant within-group differences. Scores on the 6-MW, TCS, and Down stairs
      functional tasks improved significantly following the application of menthol gel.
      Scores on the Down stairs functional task improved significantly following
      application of the placebo gel. The menthol intervention resulted in significant
      reductions in pain during the TUG, TCS, Up stairs, and Down stairs tasks. The
      placebo condition did not result in any significant changes in pain during the
      functional tasks. There were no differences detected in functional tasks or pain
      following the placebo and menthol conditions. These findings provide partial
      support regarding the efficacy of menthol gel to improve functioning and reduce
      pain among knee OA patients.

PMID- 22976811
TI  - Functional mobility limitations and falls in assisted living residents with
      dementia: physical performance assessment and quantitative gait analysis.
AB  - BACKGROUND AND PURPOSE: The prevalence of functional mobility limitations and
      falls is higher in people with dementia compared with cognitively healthy older
      adults, and both are associated with gait and motor impairments. The aims of this
      study were to examine concurrent validity of physical performance assessments and
      spatiotemporal gait measures in older adults with advanced dementia and to
      prospectively examine their relationship to functional mobility limitations and
      falls over a 4-month period. METHODS: Thirty-one older adults living in dementia
      specific assisted living residences participated. Correlations were examined
      between a modified Berg Balance Scale (mod-Berg), the Short Physical Performance
      Battery (SPPB), and spatiotemporal gait measures using the GAITRite Walkway
      system. Over 4-months, functional mobility limitations were rated, and falls were
      recorded by nursing supervisors. Differences in functional mobility limitations
      and falls were examined in relation to baseline balance and gait measures.
      RESULTS: Partial correlations between spatiotemporal gait measures and the mod
      Berg as well as the SPPB were statistically significant (P < .05) after adjusting
      for age and Mini-Mental State Examination scores. Participants with low
      functional mobility ratings had significantly lower scores on the mod-Berg (P <=
      .001) and SPPB (P <= .001). They also demonstrated slower gait speed, lower
      cadence, higher stride time variability, and a greater percentage of gait cycle
      in double support (P <= .01). Participants with at least 1 fall, compared with
      those who did not fall, had lower scores on the mod-Berg (P = .02), lower cadence
      (P = .048), and greater stride length variability (P = .035). DISCUSSION: The mod
      Berg and SPPB were strongly correlated with reliable gait measures associated
      with instability and increased fall risk. The modified Berg Balance Scale
      demonstrates potential as a predictor of falls in older adults living in dementia
      specific assisted living. CONCLUSION: The results of this study provide support
      for the application of brief physical performance assessments by physical
      therapists to identify functional mobility limitations and fall risk in older
      adults with advanced dementia.

PMID- 22976812
TI  - An isokinetic training program for reducing falls in a community-dwelling older
      adult: a case report.
AB  - BACKGROUND: With the population older than 65 years, projected to double by the
      year 2030, falls in older adults are a substantial health concern. Muscle
      strength deficits are one of the multifactorial components linked to increased
      fall risk, and decreasing these deficits has been one of the goals of
      interventions designed to decrease fall risk. These interventions have
      traditionally focused on improving peak torque; however, recent research suggests
      that exercise protocols that focus on the rate of torque development (RTD) may be
      more effective in decreasing fall risk. PURPOSE: This case report examines
      clinical outcomes following implementation of an isokinetic strengthening
      protocol coupled with a balance program designed to reduce fall risk in a
      community-dwelling older adult. METHODS: The individual was a 70-year-old woman
      with a history of 3 falls over the past 8 months and no related medical etiology
      who had self-limited her activities because of fear of another fall. She was
      classified as having substantial risk for future falls because of fall history,
      increased fear of falling, and below age norms on the Berg Balance Scale (BBS),
      and the Timed Up and Go (TUG). The treatment program consisted of 12 weeks of
      high-intensity isokinetic knee extensor training, high challenge dynamic gait and
      balance activities, and core strengthening. The isokinetic protocol consisted of
      4 sets of 10 concentric-only repetitions at speeds of 240 degrees /sec and 300
      degrees /sec for a total of 8 work sets. Dynamic gait activities incorporating
      directional and obstacle drills, and rocker and balance boards were used for
      balance training activities. Progressive theraband exercises were used for core
      strengthening. As her home program, the participant was encouraged to return to
      line dancing twice per week. During the 12-week protocol, the participant
      completed two 90-minute therapy sessions and two 90-minute dance classes per
      week. RESULTS: After the 12 weeks of treatment, knee extensor peak torque at 150
      ms improved on the right from 67.8 N to 107.1 N (57.9% increase), and on the left
      from 65.1 N to 97.6 N (49.9% increase). The BBS score improved from 45 to 52; and
      the TUG improved from 14.0 to 8.6 seconds. Both final scores exceeded fall risk
      cutoffs (BBS = 48; TUG = 13.5 seconds) and the change score exceeded minimal
      detectable change (BBS = 7; TUG 5.4 seconds). CONCLUSIONS: The treatment program
      produced improvements in knee extensor peak torque and RTD, but more importantly,
      the final scores on the clinical outcome measures placed the participant above
      established fall-risk cutoff scores. Although future research with increased
      numbers of participants and a control group should be conducted to confirm this
      study's results, these findings support the use of isokinetic training to reduce
      fall risk in older adults.

PMID- 22976813
TI  - Measuring indoor life-space mobility at home in older adults with difficulty to
      perform outdoor activities.
AB  - BACKGROUND: Measurement of indoor physical activity at home in older adults who
      have difficulty performing outdoor activities is a key to documenting baseline
      physical activity levels to guide physical activity interventions aimed at
      reducing the rate of decline in mobility. PURPOSE: The purpose of this study was
      to describe indoor life-space mobility at home (LSH) and examine the association
      between LSH and mobility-related physical functions in older adults who have
      difficulty performing outdoor activities. METHODS: The participants were 20
      community-dwelling older adults (mean age [SD], 76.6 [5.1] years) receiving home
      care rehabilitation. Participants were assessed for LSH and physical function
      related to mobility. Assessments included isometric knee extensor strength, the
      Timed Up and Go (TUG) Test, functional status (a 13-item Motor subscale of
      Functional Independence Measure, the Tokyo Metropolitan Institute of Gerontology
      Index of Competence, and outdoor life-space mobility (life-space assessment
      [LSA]). Life-space mobility at home documented how far and how often participants
      moved from a bedroom to 4 destinations (entrance, dining room, bathroom, and
      toilet) at home with or without assistance during the week prior to the
      assessment. RESULTS: Reliability of LSH was high (intraclass correlation
      coefficient [ICC] (1,1) = 0.80, ICC (1,2) = 0.89). Simple bivariate correlations
      showed a significant relationship between LSH and isometric knee extensor
      strength (rs = 0.59, P = .01) and TUG Test (rs = -0.74 P = .01). Life-space
      mobility at home showed moderate correlations with the Functional Independence
      Measure (rs = 0.58, P = .01) and Tokyo Metropolitan Institute of Gerontology
      Index of Competence (rs = 0.49, P = .03), but no significant correlation with the
      LSA (rs = 0.33, P = .17). DISCUSSION: Regarding intrarater reliability, the ICCs
      for measuring the LSH indicated high reproducibility. The results suggest that
      the LSA mainly reflects outdoor life-space mobility and activity rather than
      indoor life-space whereas the LSH reflects indoor life-space mobility and is
      considered an indicator of a major decline in indoor activities and physical
      abilities. CONCLUSIONS: The LSH concept can measure with high reliability and
      concurrent or discriminant validity, and it is a different concept from outdoor
      life-space mobility. Life-space mobility at home may be an important factor
      associated with physical functions related to mobility and functional status, and
      measuring LSH may be useful to assess current indoor life-space activity in older
      adults who have difficulty performing outdoor activities.

PMID- 22976814
TI  - Implementing a cognitive-behavioral pain self-management program in home health
      care, part 1: program adaptation.
AB  - BACKGROUND AND PURPOSE: Pain is highly prevalent among older adults receiving
      home care, contributing to disability, increased health care utilization, nursing
      home placement, and diminished quality of life. Pain is a particular problem in
      the home care setting, where current approaches are often inadequate, resulting
      in persistent high levels of pain and disability in this vulnerable population.
      Cognitive-behavioral approaches to pain management have demonstrated
      effectiveness in reducing pain intensity and associated disability but have not
      been systematically implemented in home health care. The purpose of this project
      was to adapt a community-based, cognitive-behavioral pain self-management program
      designed for patients with persistent back pain for implementation by physical
      therapists (PTs) to use with patients with activity-limiting pain in the home
      care setting. METHODS: In this observational study, 2 groups of PTs practicing in
      home care were trained in the community-based program and completed surveys and
      participated in discussions during the training workshops to gather input on the
      program components perceived to be most helpful for their patients with pain;
      modifications to the program and the patient education materials for use in home
      care; and recommendations concerning program training and support required for
      successful implementation. Data collected during the workshops were summarized
      and presented to 2 expert panels for additional input and final decisions
      regarding program adaptations. RESULTS: Seventeen PTs with an average of 16.6
      years of practice as a PT received the training and provided input on the
      community-based program. Program modifications based upon PT and expert panel
      review included reduction in the number of sessions, deletion of content,
      modification of the exercise component of the program, revision of patient
      materials, and modification of therapist training. DISCUSSION/CONCLUSIONS: This
      study successfully adapted a group-based pain management program for
      implementation by health care providers in a home care setting. The process
      described here may be useful for other groups planning to implement evidence
      based programs in new settings. Part 2 of this study, a companion article in this
      issue, describes the field-testing of this home-care adapted program.

PMID- 22976815
TI  - Implementing a cognitive-behavioral pain self-management program in home health
      care, part 2: feasibility and acceptability cohort study.
AB  - PURPOSE: The prevalence of pain in older adults receiving home health care is
      high, yet safety concerns for analgesic therapy point to a need for
      nonpharmacologic approaches to pain management in this population. The purpose of
      this study was to determine the feasibility and acceptability to physical
      therapists (PTs) and patients of a cognitive-behavioral pain self-management
      (CBPSM) program. METHODS: Thirty-one PTs volunteered to participate, completed
      two 4-hour training sessions, and recruited 21 patients with activity-limited
      pain who consented to participate in the study. Physical therapists completed pre
      and posttest assessments of CBPSM knowledge at the first training session,
      provided structured survey feedback after the second training session, and
      responded to a phone survey 3 months after training. Patients provided feedback
      during weekly phone interviews, while receiving the CBPSM program. Treatment
      sessions were audiotaped during delivery of the self-management pain protocol.
      Audiotapes were evaluated by independent raters for program fidelity. RESULTS:
      Participating PTs were experienced in physical therapy (average 16.5 years) and
      in home health care (average 11.0 years). Analysis of pre- and posttest data
      showed that PTs' CBPSM knowledge increased from a pretest mean of 60.9% to a
      posttest mean of 85.9%. Audiotape analysis indicated 77.7% therapist adherence to
      the protocol. At 3-month follow-up, 24.0% of therapists continued to use the
      entire protocol with their patients presenting with activity-limiting pain.
      Patient data show high rates of patient recall of being taught protocol
      components, trying components at least once (ranging from 84.4% to 100.0%) and
      daily use of protocol components (ranging from 47.3% to 68.4%). The percentage of
      patients finding a technique helpful for pain management ranged from 71.4% to
      81.2%. CONCLUSION: This study offers preliminary data on the use of
      nonpharmacologic pain self-management strategies by PTs in home health setting.
      Positive feedback from PTs and patients suggests that the translated protocol is
      both feasible and acceptable.

PMID- 22976817
TI  - Custom-made, selective laser sintering (SLS) blade implants as a non-conventional
      solution for the prosthetic rehabilitation of extremely atrophied posterior
      mandible.
AB  - The treatment of severely atrophied posterior mandibles with standard-diameter
      root-form implants may present a challenge. Bone reconstructive surgery
      represents the treatment of choice; however, it may not be accepted by some
      patients for economic reasons or due to higher morbidity. Computer-aided
      design/computer-aided manufacturing (CAD/CAM) technologies have recently opened
      new frontiers in biomedical applications. Selective laser sintering (SLS) is a
      CAD/CAM technique that allows the fabrication of complex three-dimensional (3D)
      structures created by computer-generated image-based design techniques. The aim
      of this study is to present a protocol for the manufacture and clinical use of
      custom-made SLS titanium blade implants as a non-conventional therapeutic
      treatment for the prosthetic rehabilitation of extremely atrophied posterior
      mandibles. Computed tomography datasets of five patients were transferred to a
      specific reconstruction software, where a 3D projection of the atrophied mandible
      was obtained, and custom-made endosseous blade implants were designed. The custom
      made implants were fabricated with SLS technique, placed in the extremely
      atrophied posterior (<4 mm width) mandible, and immediately restored with fixed
      partial restorations. After 2 years of loading, all implants were in function,
      showing a good esthetic integration. Blade implants can be fabricated on an
      individual basis as a custom-designed device. This non-conventional approach may
      represent an option for restoring the atrophied posterior mandible of elderly
      patients. 

PMID- 22976818
TI  - In situ monitoring Alzheimer's disease beta-amyloid aggregation and screening of
      Abeta inhibitors using a perylene probe.
AB  - A cationic perylene tetracarboxylic acid diimide derivative (1) is employed as a
      probe for in situ monitoring of Abeta aggregation and screening Abeta inhibitors.
      The assay is based on the fluorescence change through the aggregation of compound
      1 following Abeta assembly. Importantly, this probe, compared with the well known
      amyloid-staining compound thioflavin T (ThT), is more sensitive to Abeta
      oligomer, which is highly toxic and plays a crucial role in the early stages of
      Alzheimer's disease.

PMID- 22976819
TI  - A kinetic-metabolic model based on cell energetic state: study of CHO cell
      behavior under Na-butyrate stimulation.
AB  - A kinetic-metabolic model approach describing and simulating Chinese hamster
      ovary (CHO) cell behavior is presented. The model includes glycolysis, pentose
      phosphate pathway, TCA cycle, respiratory chain, redox state and energetic
      metabolism. Growth kinetic is defined as a function of the major precursors for
      the synthesis of cell building blocks. Michaelis-Menten type kinetic is used for
      metabolic intermediates as well as for regulatory functions from energy shuttles
      (ATP/ADP) and cofactors (NAD/H and NADP/H). Model structure and parameters were
      first calibrated using results from bioreactor cultures of CHO cells expressing
      recombinant t-PA. It is shown that the model can simulate experimental data for
      all available experimental data, such as extracellular glucose, glutamine,
      lactate and ammonium concentration time profiles, as well as cell energetic
      state. A sensitivity analysis allowed identifying the most sensitive parameters.
      The model was then shown to be readily adaptable for studying the effect of
      sodium butyrate on CHO cells metabolism, where it was applied to the cases with
      sodium butyrate addition either at mid-exponential growth phase (48 h) or at the
      early plateau phase (74 h). In both cases, a global optimization routine was used
      for the simultaneous estimation of the most sensitive parameters, while the
      insensitive parameters were considered as constants. Finally, confidence
      intervals for the estimated parameters were calculated. Results presented here
      further substantiate our previous findings that butyrate treatment at mid
      exponential phase may cause a shift in cellular metabolism toward a sustained and
      increased efficiency of glucose utilization channeled through the TCA cycle.

PMID- 22976820
TI  - Prevalence of Nitrosomonas cluster 7 populations in the ammonia-oxidizing
      community of a submerged membrane bioreactor treating urban wastewater under
      different operation conditions.
AB  - A pilot-scale ultrafiltration membrane bioreactor (MBR) was used for the aerobic
      treatment of urban wastewater in four experimental stages influenced by seasonal
      temperature and different sets of operation conditions. The structure of the
      ammonia-oxidizing bacteria (AOB) community was profiled by temperature gradient
      gel electrophoresis (TGGE), based on the amplification and separation of partial
      ammonia-monoxygenase subunit A (amoA) genes. Canonical correspondence analysis
      revealed that temperature, hydraulic retention time and percentage of ammonia
      removal had a significant effect on the fingerprints of AOB communities.
      Phylogenetic analysis conducted on amoA/AmoA sequences of reamplified TGGE bands
      showed, however, that closely related ammonia-oxidizing populations inhabited the
      sludge of the MBR in all experimental stages. Nitrosomonas cluster 7 populations
      (N. europaea-N. eutropha cluster) prevailed under all conditions tested, even
      when the MBR was operated under complete biomass retention or at low
      temperatures, suggesting that the high ammonia concentrations in the system were
      determinant to select r-strategist AOB.

PMID- 22976821
TI  - A critique of available scales and presentation of the Non-Human Primate
      Dyskinesia Rating Scale.
AB  - Levodopa-induced dyskinesia (LID) is a major limitation of long-term management
      of Parkinson's disease. The roadblocks that have hindered the development of new
      treatments for levodopa-induced dyskinesia were discussed at a meeting organized
      by the Michael J. Fox Foundation for Parkinson's research (New York, NY, March
      2011). Among these, the lack of consensus methodology and clinical applicability
      for eliciting and rating LID in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-treated monkeys was highlighted as a particular concern. Here we present
      an update on the practical use of rating scales for evaluating LID in MPTP
      lesioned primate models of PD, with a focus on macaques, and present specifics on
      the Non-Human Primate Dyskinesia Rating Scale.

PMID- 22976822
TI  - Concise construction of the tetracyclic core of lycorine-type alkaloids and the
      formal synthesis of alpha-lycorane based on asymmetric bifunctional thiourea
      catalyzed cascade reaction.
AB  - A concise and stereoselective construction of the tetracyclic core of lycorine
      type alkaloids and the formal synthesis of alpha-lycorane has been achieved. The
      feature of the current method is the employment of a bifunctional thiourea
      catalyzed cascade reaction as a powerful tool to construct the skeleton of the
      natural product, which is a challenging yet very rarely explored strategy. As a
      result, the tetracyclic core is efficiently synthesized in just three simple
      operations involving two consecutive cascade reactions.

PMID- 22976823
TI  - Evolving global education standards for nurses and midwives.
AB  - More than a a decade ago nurse experts identified information critical for their
      practice in the 21st century, initiated by the increasing globalization of
      healthcare and nursing education. Much has happened since then. We know more
      about the healthcare needs of developing and developed countries, although
      solutions remain problematic. Although nurses continue to migrate, exaggerating
      developing country health issues, they are plagued by the variability in how they
      are educated. For example, some countries prepare nurses in high school, while in
      other countries nurses are educated in institutions of higher education.
      Recognizing this variability, nurse leaders have undertaken several efforts to
      address this variability. The purpose of this article is to highlight several
      issues associated with global education in general, describe current efforts in
      nursing and midwifery to strengthen nursing education, and discuss why these
      efforts are relevant to maternal-child nurses. This information is particularly
      relevant when one considers the contributions appropriately educated nurses and
      midwives can make as achieving select United Nations Millennium Development
      Goals.

PMID- 22976824
TI  - Sex differences in periodontal disease in catastrophic and attritional
      assemblages from medieval London.
AB  - Periodontal disease is one of the most common chronic diseases in living
      populations, and most studies that have examined sex differences in periodontal
      disease have found higher frequencies in men compared to women. This study
      examines sex differences in periodontal disease in two cemeteries from medieval
      London: the East Smithfield cemetery (c. 1349-1350), an exclusively Black Death
      cemetery that represents catastrophic mortality (n = 161), and the St. Mary
      Graces cemetery (c. 1350-1538), a post-Black Death attritional assemblage that
      represents normal medieval mortality (n = 100). The results reveal a
      significantly higher frequency of periodontal disease, independent of age, among
      males compared with females in St. Mary Graces, but no significant difference
      between the sexes in East Smithfield. The sex differences in the attritional
      assemblage might reflect heightened susceptibility to periodontal disease in the
      living population or sex differences in frailty. The differences in the sex
      patterns of periodontal disease between the two cemeteries might be the result of
      disproportionately negative effects of the Great Bovine Pestilence and consequent
      decreases in dairy availability on female oral health among victims of the Black
      Death.

PMID- 22976825
TI  - Iron-catalyzed C-H hydroxylation and olefin cis-dihydroxylation using a single
      electron oxidant and water as the oxygen-atom source.

PMID- 22976830
TI  - CCL2 released at tumoral level contributes to the hyperalgesia evoked by
      intratibial inoculation of NCTC 2472 but not B16-F10 cells in mice.
AB  - The participation of the chemokine CCL2 (monocyte chemoattractant protein-1) in
      inflammatory and neuropathic pain is well established. Furthermore, the release
      of CCL2 from a NCTC 2472 cells-evoked tumor and its involvement in the
      upregulation of calcium channel alpha2delta1 subunit of nociceptors was
      demonstrated. In the present experiments, we have tried to determine whether the
      increase in CCL2 levels is a common property of painful tumors and, in
      consequence, the administration of a chemokine receptor type 2 (CCR2) antagonist
      can inhibit tumoral hypernociception. CCL2 levels were measured by ELISA in the
      tumoral region of mice intratibially inoculated with NCTC 2472 or B16-F10 cells,
      and the antihyperalgesic and antiallodynic effects evoked by the administration
      of the selective CCR2 antagonist RS 504393 were assessed. Cultured NCTC 2472
      cells release CCL2 and their intratibial inoculation evokes the development of a
      tumor in which CCL2 levels are increased. Moreover, the systemic or peritumoral
      administration of RS 504393 inhibited thermal and mechanical hyperalgesia, but
      not mechanical allodynia evoked after the inoculation of these cells. Thermal
      hyperalgesia was also inhibited by the peritumoral administration of a
      neutralizing CCL2 antibody. In contrast, no change in CCL2 levels was observed in
      mice inoculated with B16-F10 cells, and RS 504393 did not inhibit the
      hypernociceptive reactions evoked by their intratibial inoculation. The
      peripheral release of CCL2 is involved in the development of thermal and
      mechanical hyperalgesia, but not mechanical allodynia evoked by the inoculation
      of NCTC 2472 cells, whereas this chemokine seems unrelated to the
      hypernociception induced by B16-F10 cells.

PMID- 22976831
TI  - The use of the "preclosure" technique for antegrade aspiration thrombectomy with
      large catheters in acute limb ischemia.
AB  - PURPOSE: This study was designed to assess retrospectively short- and mid-term
      outcomes of the use of a suture-mediated closure device to close the antegrade
      access in patients undergoing percutaneous aspiration thrombectomy with large
      catheters for acute leg ischemia. METHODS: Between November 2005 and February
      2010, a suture-mediated active closure system (ProGlide((r)) 6F, Abbott) was
      placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101
      patients (74 men, 73 %, mean age 70.1 +/- 12.6 years standard deviation). Data
      regarding mortality, complications, and factors contributing to vascular
      complications at the access site was collected for 6 month after the intervention
      to detect device-related problems. As a coincidence, 77 patients had follow-up
      visits for a duplex ultrasound. RESULTS: There were a total of 19 vascular
      complications (19 %) at the puncture site, all of which were of hemorrhagic
      nature and none of which consisted of vessel occlusion. Two major outcome
      complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal
      bleeding required additive treatment and did not result in permanent sequelae.
      Nine cases involved death of which eight were not attributable to the closure and
      one remained unclear. Successful closure was achieved in 95 patients (94 %);
      additional manual compression was sufficient in the majority of the remaining
      patients. Numerous factors contributing to vascular complications were
      encountered. CONCLUSIONS: With acceptable short- and mid-term outcomes, the
      "preclose" technique can be a reliable option for the closure of a large
      antegrade femoral access even for patients at a high risk of vascular
      complications, such as those undergoing aspiration thrombectomy.

PMID- 22976832
TI  - Treatment of disease recurrence after allogeneic hematopoietic stem cell
      transplantation in children with juvenile myelomonocytic leukemia: a great
      challenge still to be won.

PMID- 22976833
TI  - The electronic and chemical structure of the a-B3CO0.5:Hy-to-metal interface from
      photoemission spectroscopy: implications for Schottky barrier heights.
AB  - The electronic and chemical structure of the metal-to-semiconductor interface was
      studied by photoemission spectroscopy for evaporated Cr, Ti, Al and Cu overlayers
      on sputter-cleaned as-deposited and thermally treated thin films of amorphous
      hydrogenated boron carbide (a-B(x)C:H(y)) grown by plasma-enhanced chemical vapor
      deposition. The films were found to contain ~10% oxygen in the bulk and to have
      approximate bulk stoichiometries of a-B(3)CO(0.5):H(y). Measured work functions
      of 4.7/4.5 eV and valence band maxima to Fermi level energy gaps of 0.80/0.66 eV
      for the films (as-deposited/thermally treated) led to predicted Schottky barrier
      heights of 1.0/0.7 eV for Cr, 1.2/0.9 eV for Ti, 1.2/0.9 eV for Al, and 0.9/0.6
      eV for Cu. The Cr interface was found to contain a thick partial metal oxide
      layer, dominated by the wide-bandgap semiconductor Cr(2)O(3), expected to lead to
      an increased Schottky barrier at the junction and the formation of a space-charge
      region in the a-B(3)CO(0.5):H (y) layer. Analysis of the Ti interface revealed a
      thick layer of metal oxide, comprising metallic TiO and Ti (2)O (3), expected to
      decrease the barrier height. A thinner, insulating Al(2)O(3) layer was observed
      at the Al-to-a-B(3)CO(0.5):H(y) interface, expected to lead to tunnel junction
      behavior. Finally, no metal oxides or other new chemical species were evident at
      the Cu-to-a-B(3)CO(0.5):H(y) interface in either the core level or valence band
      photoemission spectra, wherein characteristic metallic Cu features were observed
      at very thin overlayer coverages. These results highlight the importance of thin
      film bulk oxygen content on the metal-to-semiconductor junction character as well
      as the use of Cu as a potential Ohmic contact material for amorphous hydrogenated
      boron carbide semiconductor devices such as high-efficiency direct-conversion
      solid-state neutron detectors.

PMID- 22976834
TI  - Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature
      aging.
AB  - mnd2 mice die prematurely as a result of neurodegeneration 30-40 days after birth
      due to loss of the enzymatic activity of the mitochondrial quality control
      protease HtrA2/Omi. Here, we show that transgenic expression of human HtrA2/Omi
      in the central nervous system of mnd2 mice rescues them from neurodegeneration
      and prevents their premature death. Interestingly, adult transgenic mnd2 mice
      develop accelerated aging phenotypes, such as premature weight loss, hair loss,
      reduced fertility, curvature of the spine, heart enlargement, increased
      autophagy, and death by 12-17 months of age. These mice also have elevated levels
      of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our
      results provide direct genetic evidence linking mitochondrial protein quality
      control to mtDNA deletions and aging in mammals.

PMID- 22976835
TI  - Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve
      injury.
AB  - Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic
      nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1
      (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK)
      kinase kinase and has an important role in stress-induced RGC apoptosis. In this
      study, we found that ONI-induced p38 activation and RGC loss were suppressed in
      ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI
      treatment with a p38 inhibitor into the eyeball was effective for RGC protection.
      ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial
      accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the
      productions of tumor necrosis factor and inducible nitric oxide synthase in
      microglia were decreased when the ASK1-p38 pathway was blocked. These results
      suggest that ASK1 activation in both neural and glial cells is involved in neural
      cell death, and that pharmacological interruption of ASK1-p38 pathways could be
      beneficial in the treatment of ONI.

PMID- 22976836
TI  - TAp73 is required for macrophage-mediated innate immunity and the resolution of
      inflammatory responses.
AB  - The multiple isoforms of p73, a member of the p53 family, share the ability to
      modulate p53 activities but also have unique properties, leading to a complex and
      poorly understood functional network. In vivo, p73 isoforms have been implicated
      in tumor suppression (TAp73(-/-) mice), DNA damage (DeltaNp73(-/-) mice) and
      development (p73(-/-) mice). In this study, we investigated whether TAp73
      contributes to innate immunity and septic shock. In response to a lethal
      lipopolysaccharide (LPS) challenge, TAp73(-/-) mice showed higher blood levels of
      proinflammatory cytokines and greater mortality than their wild-type littermates.
      In vitro, TAp73(-/-) macrophages exhibited elevated production of tumor necrosis
      factor alpha , interleukin-6 and macrophage inflammatory protein-2 as well as
      prolonged survival, decreased phagocytosis and increased major histocompatibility
      complex class II expression. Mice depleted of endogenous macrophages and
      reconstituted with TAp73(-/-) macrophages showed increased sensitivity to LPS
      challenge. These results suggest that macrophage polarization is altered in the
      absence of TAp73 such that maintenance of the M1 effector phenotype is prolonged
      at the expense of the M2 phenotype, thus impairing resolution of the inflammatory
      response. Our data indicate that TAp73 has a role in macrophage polarization and
      innate immunity, enhancing the action field of this important regulatory
      molecule.

PMID- 22976837
TI  - Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in
      neurons.
AB  - Short-term proteasome inhibition has been shown to prevent neuronal apoptosis.
      However, the key pro-survival proteins that must be degraded for triggering
      neuronal death are mostly unknown. Here, we show that Mcl-1, an anti-apoptotic
      Bcl-2 family member, is degraded by the proteasome during neuronal apoptosis.
      Using primary cultures of cerebellar granule neurons deprived of serum and KCl,
      we found that ubiquitination and proteasomal degradation of Mcl-1 depended on its
      prior phosphorylation by GSK3, providing the first insight into post
      translational regulation of Mcl-1 in neurons. In a previous study, we have
      reported that the E3 ubiquitin-ligase Trim17 is both necessary and sufficient for
      neuronal apoptosis. Here, we identified Trim17 as a novel E3 ubiquitin-ligase for
      Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl
      1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a
      phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17
      expression reduced both ubiquitination and degradation of Mcl-1 in neurons.
      Moreover, impairment of Mcl-1 phosphorylation, by kinase inhibition or point
      mutations, not only decreased ubiquitination and degradation of Mcl-1, but also
      blocked the physical interaction between Trim17 and Mcl-1. As this stabilization
      of Mcl-1 increased its neuroprotective effect, our data strongly suggest that
      Trim17-mediated ubiquitination and degradation of Mcl-1 is necessary for
      initiating neuronal death.

PMID- 22976838
TI  - EphA/ephrin-A signaling is critically involved in region-specific apoptosis
      during early brain development.
AB  - EphAs and ephrin-As have been implicated in the morphogenesis of the developing
      brain. We found that EphA7 and ephrin-A5 are coexpressed in the dorsal midline
      (DM) of the diencephalon and anterior mesencephalon. Interestingly, programmed
      cell death (PCD) of the neural epithelial cells normally found in this region was
      reduced in ephrin-A5/ephrin-A2 dual-deficient embryos. In contrast, in vivo
      expression of ephrin-A5-Fc or full-length ephrin-A5 strongly induced apoptosis in
      neural epithelial cells and was accompanied by severe brain malformation during
      embryonic development. Expression of ephrinA5-Fc correlated with apoptosis of
      EphA7-expressing cells, whereas null mutation of ephrin-A5 resulted in the
      converse phenotype. Importantly, null mutation of caspase-3 or endogenous ephrin
      A5 attenuated the PCD induced by ectopically overexpressed ephrin-A5. Together,
      our results suggest that brain region-specific PCD may occur in a region where
      EphAs cluster with neighboring ephrin-As through cell-cell contact.

PMID- 22976839
TI  - NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M)
      polymorphisms segregate the risk of childhood acute leukemias according to age
      range distribution.
AB  - PURPOSE: The risk of developing childhood leukemia has been associated with gene
      polymorphisms that decrease the activity of detoxifying metabolic enzymes and
      enzymes involved in systemic oxidative stress. We investigated the NQO1 and PON1
      polymorphisms for associations with susceptibility to childhood leukemia.
      METHODS: Samples from 1,027 Brazilian children (519 acute lymphoblastic leukemia,
      ALL; 107 acute myeloid leukemia, AML; 401 controls) were analyzed. TaqMAN real
      time assays were used to determine the NQO1 rs1800566 (C609T), PON1 rs662
      (Q192R), and PON1 rs854560 (L55M) frequencies. Logistic regression was used to
      evaluate the association of polymorphisms with cases and controls, with age and
      somatic fusion genes (MLL-r and ETV6-RUNX1) as covariables. RESULTS: Children
      with at least one NQO1 variant allele were at lower risk for developing infant
      AML (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10-0.68); no
      association was detected for ALL. PON1 rs854560 (L55M) was associated with an
      increased risk of developing childhood leukemia (LM + MM, OR 1.93, 95 % CI 1.32
      2.81). The PON1 rs662 R192R genotype had a statistically significant decreased
      frequency in ALL (OR 0.64, 95 % CI 0.43-0.93). Infant ALL cases were more likely
      to harbor homozygous PON1 rs854560 alleles than controls (OR 1.72, 95 % CI 1.03
      2.89); at least one M allele was associated with an increased risk of ALL in
      children older than 1 year (OR 1.99, 95 % CI 1.17-3.3). CONCLUSIONS: The NQO1
      rs1800566 (C609T), PON1 rs854560 (L55M), and PON1 rs662 (Q192R) polymorphisms
      modified risk depending on leukemia subtype (decreased in AML, increased and
      decreased in ALL, respectively), age strata, and variant genotype combinations.

PMID- 22976840
TI  - Physiological and behavioral engagement in social contexts as predictors of
      adolescent depressive symptoms.
AB  - Depressive symptoms are considered to have evolutionary social functions to
      reduce social risks with peers and family members. However, social processes and
      their relationship to depressive symptoms have been understudied in adolescent
      boys. Low engagement in social contexts may predict depressive symptoms in
      adolescent boys, as it may signify efforts to reduce social risks. To address
      these issues, this study focused on 160 boys at risk for affective problems based
      on low socioeconomic status. We evaluated how behavioral and physiological
      engagement in peer and family contexts, respectively, in late childhood predicted
      depressive symptoms at age 12 and age 15. Social withdrawal was measured across
      late childhood (ages 9-12) in a camp setting using a latent variable of teacher
      ratings of withdrawn behavior, peer nominations of withdrawn behavior, and camp
      counselor ratings of withdrawn behavior. Physiological reactivity was measured
      during a provocative parent-child conversation using respiratory sinus arrhythmia
      (RSA) at age 12. Social withdrawal in late childhood predicted depressive
      symptoms at age 12. The combination of high levels of social withdrawal with
      peers from ages 9-12 and low RSA reactivity with a parent at age 12 predicted
      higher depressive symptoms at age 15. Withdrawal in multiple social contexts may
      place boys at risk for depressive symptoms during the vulnerable period of
      adolescence. 

PMID- 22976841
TI  - Perfluorooctane sulfonate induces apoptosis in lung cancer A549 cells through
      reactive oxygen species-mediated mitochondrion-dependent pathway.
AB  - Perfluorooctane sulfonate (PFOS) is a widespread environmental contaminant that
      is detected in the lung of mammals. The mechanisms underlying PFOS-induced lung
      cytotoxicity remain unclear. The main purpose of this study was to evaluate the
      cytotoxic effects of PFOS on human lung cancer A549 cells and its possible
      molecular mechanism. A549 cells were treated with PFOS (0, 25, 50, 100 and 200
      MUm) and the cellular apoptosis, mitochondrial membrane potential as well as
      intracellular reactive oxygen species were determined. In this study, PFOS
      induced a dose-dependent increase in A549 cell toxicity via an apoptosis pathway
      as characterized by increased percentage of sub-G1, activation of caspase-3 and 
      9, and increased ratio of Bax/bcl-2 mRNA expression. In addition, there was
      obvious oxidative stress, represented by decreased glutathione level, increased
      malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an
      antioxidant that is a direct reactive oxygen species scavenger, can effectively
      block PFOS-induced reactive oxygen species generation, mitochondrial membrane
      potential loss and cell apoptosis. These data indicate that PFOS induces
      apoptosis in A549 cells through a reactive oxygen species-mediated mitochondrial
      dysfunction pathway mechanism.

PMID- 22976842
TI  - Planar-chiral [7]orthocyclophanes.

PMID- 22976843
TI  - Revealing phosphoproteins playing role in tobacco pollen activated in vitro.
AB  - The transition between the quiescent mature and the metabolically active
      germinating pollen grain most probably involves changes in protein
      phosphorylation status, since phosphorylation has been implicated in the
      regulation of many cellular processes. Given that, only a minor proportion of
      cellular proteins are phosphorylated at any one time, and that phosphorylated and
      nonphosphorylated forms of many proteins can co-exist within a cell, the
      identification of phosphoproteins requires some prior enrichment from a crude
      protein extract. Here, we have used metal oxide/hydroxide affinity chromatography
      (MOAC) based on an aluminum hydroxide matrix for this purpose, and have generated
      a population of phosphoprotein candidates from both mature and in vitro activated
      tobacco pollen grains. Both electrophoretic and nonelectrophoretic methods,
      allied to MS, were applied to these extracts to identify a set of 139
      phosphoprotein candidates. In vitro phosphorylation was also used to validate the
      spectrum of phosphoprotein candidates obtained by the MOAC phosphoprotein
      enrichment. Since only one phosphorylation site was detected by the above
      approach, titanium dioxide phosphopeptide enrichment of trypsinized mature pollen
      crude extract was performed as well. It resulted in a detection of additional 51
      phosphorylation sites giving a total of 52 identified phosphosites in this set of
      139 phosphoprotein candidates.

PMID- 22976844
TI  - Current issues in gastric cancer management.

PMID- 22976846
TI  - Contextual influences of dimension, speed, and direction of motion on subjective
      time perception.
AB  - Research has indicated that the direction of motion and the speed of motion can
      influence the subjective estimates of temporal duration of two-dimensional (2-D)
      stimuli expanding and contracting within the picture plane. In this study, we
      investigated whether the contextual cues of stimulus/movement-plane
      dimensionality (2-D stimuli with implied movement in the picture plane or depth
      rendered "3-D" stimuli with implied movement in the depth plane) influence and
      interact with speed and implied movement direction during interval estimation.
      Participants viewed a series of standard stimulus durations followed by a test
      stimulus duration and determined whether the test and standard durations
      differed. The results indicated that moving stimuli were overestimated relative
      to stationary stimuli, regardless of the direction of motion or dimensionality.
      Also, faster-moving stimuli were overestimated relative to slower-moving stimuli.
      Importantly, an interaction between movement direction and dimensional cues
      indicated that the loom/recede distinction occurs for 2-D but not for 3-D
      stimuli. It is possible that the loom/recede distinction for the 2-D condition
      may be an artifact arising from reduced or from a lack of perceived motion in 2-D
      "recede" conditions, rather than a specific overestimation for looming stimuli.

PMID- 22976847
TI  - Unsedated transnasal upper gastrointestinal endoscopy has favorable diagnostic
      effectiveness, cardiopulmonary safety, and patient satisfaction compared with
      conventional or sedated endoscopy.
AB  - BACKGROUND: To assess the diagnostic effectiveness, cardiopulmonary safety, and
      patient comfort of transnasal endoscopy (TNE), compared with conventional
      endoscopy (CES) and sedated endoscopy (SES), and to compare procedural risks and
      patient satisfaction/preference. METHODS: In this prospective, randomized, and
      controlled protocol, eligible patients (n = 397) in an outpatient clinic were
      randomized to CES (n = 133), SES (n = 134), or unsedated TNE (n = 130) due to
      upper gastrointestinal (GI) complaints. Patients were continuously monitored for
      systolic/diastolic blood pressure (SBP/DBP), pulse rate (PR), and SpO(2)
      throughout the endoscopy. All subjects (n = 392) completing their assigned
      endoscopy were asked to evaluate endoscopy satisfaction, pain, and
      nausea/vomiting on visual analog scales. Patient preference for the assigned
      endoscopy was assessed against previous endoscopy experience or by willingness to
      repeat the assigned endoscopy. RESULTS: Endoscopic outcomes for the esophagus,
      stomach, and duodenum were comparable among the three groups. SBP/DBP and PR were
      more stable in patients undergoing TNE than in those undergoing CES or SES, while
      SpO(2) remained stable and above 95% among all three groups. Patients were more
      satisfied with TNE than with CES and experienced less pain and nausea/vomiting.
      Patients exhibited a high preference for SES, whereas 67.6% of patients who
      previously underwent SES and were randomly assigned to TNE were willing to
      undergo TNE again. CONCLUSIONS: TNE has comparable diagnostic effectiveness to
      CES and SES, but is less stressful on cardiopulmonary function, indicating that
      TNE is a more comfortable, preferred, and cost-effective endoscopic technique
      than CES and SES.

PMID- 22976849
TI  - Aryne cycloaddition with 3-oxidopyridinium species.
AB  - The [3 + 2] cycloaddition of arynes with 3-oxidopyridinium species is examined
      using the Kobayashi benzyne precursor. The reaction affords a bicyclo[3.2.1]
      skeleton under mild conditions. A [7 + 2] cycloaddition mode with a subsequent
      pyridine ring-opening event has also been observed.

PMID- 22976848
TI  - Brain organochlorines and Lewy pathology: the Honolulu-Asia Aging Study.
AB  - Although organochlorines have been reported more frequently in Parkinson's
      disease (PD) brains than in controls, the association with brain Lewy pathology
      is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to
      organochlorines from a variety of sources during midlife, represent a population
      well suited to determining the relationship of brain organochlorines with Lewy
      pathology in decedents from the longitudinal HAAS. The study design included the
      measurement of 21 organochlorine levels in frozen occipital lobe samples from
      HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used
      to identify Lewy bodies and Lewy neurites. With the potential for spurious
      associations to appear between Lewy pathology and 17 organochlorine compounds
      found in at least 1 brain, initial assessments identified heptachlor epoxide
      isomer b, methoxychlor, and benzene hexachloride b as being most important. The
      prevalence of Lewy pathology was 75% (6 of 8) among brains with any 2 of the 3
      compounds, 48.8% (79 of 162) among those with 1, and 32.7% (18 of 55) for those
      with neither (P = .007 test for trend). Although findings persisted after
      removing cases with PD and dementia with Lewy bodies and after adjustment for age
      at death, body mass index, pack-years of cigarette smoking, and coffee intake (P
      = .013), the results were insignificant when correcting for multiple testing.
      Although consistent with earlier accounts of an association between
      organochlorines and clinical PD, associations with Lewy pathology warrant further
      study.

PMID- 22976850
TI  - Severe bronchiolitis in infancy: can asthma in adolescence be predicted?
AB  - Bronchiolitis in infancy is a risk factor for development of asthma in the first
      decades of life, although the majority may be asymptomatic at school age.
      Respiratory symptoms are common in early life, and prediction of later asthma may
      be challenging. We aimed to study if simple clinical variables assessed at 2
      years of age could predict asthma at 11 years of age and thereby provide a basis
      for follow-up and treatment after bronchiolitis in infancy. The study included
      105 children hospitalized for bronchiolitis during their first year of life. Of
      these, 101 (96.2%) participated in the first follow-up at 2 years of age and 93
      (88.6%) in the second follow-up at age 11. The overall prevalence of asthma at 11
      years of age was 22.6%. Among the risk factors assessed at 2 years of age,
      recurrent wheeze appeared most important (odds ratio for later asthma: 7.2; 95%
      confidence interval: 1.3, 41.6; P = 0.015). Tested separately, recurrent wheeze
      had high sensitivity (90.5%), but low specificity (58.3%), low negative
      likelihood ratio (LR) (0.2) and low negative post-test probability (4.5%);
      indicating that absence of recurrent wheeze was better suited to exclude than to
      predict asthma at 11 years of age. Combining recurrent wheeze with either
      parental atopy, parental asthma or atopic dermatitis improved the specificity
      (>80), positive LR (>3) and positive post-test probability (~50%), rendering the
      combinations more appropriate for the prediction of later asthma. In conclusion,
      after bronchiolitis in infancy, simple clinical non-invasive variables assessed
      at 2 years of age could predict asthma at 11 years of age with reasonable
      accuracy. However, the data were better suited to exclude than to predict later
      asthma.

PMID- 22976851
TI  - Dye encapsulation inside a new mesoporous metal-organic framework for
      multifunctional solvatochromic-response function.

PMID- 22976852
TI  - Synthesis and characterization of doxorubicin-loaded poly(lactide-co-glycolide)
      nanoparticles as a sustained-release anticancer drug delivery system.
AB  - The objective of the present study was to prepare a polymeric drug delivery
      system with no burst effect. To attain this goal, doxorubicin (Dox) as an
      effective anticancer drug was loaded into poly(lactide-co-glycolide) (PLGA)
      nanoparticles (NPs) to improve the drug performance and also maximize the release
      period. After the synthesis process, the freshly made PLGA NPs with two different
      lactide-to-glycolide ratios (75:25 and 50:50) were evaluated physically and
      chemically. To determine the encapsulation efficiency, a centrifugation method
      was applied. Also, the drug loading effect on particle size, polydispersity
      index, and zeta potential was examined. The results indicated that the NPs had
      nearly the same diameters around 360 nm, and the entrapment efficiencies for
      75:25 PLGA and 50:50 PLGA were reported around 39 and 48 %, respectively. A
      slight increase in all parameters was observed due to the increase of the drug
      loading content. The primary release was 7.91 % (w/w) and 14.70 % (w/w) for 75:25
      and 50:50 drug-loaded NPs, respectively; no burst effect was observed. After 20
      days, the drug release was around 70.98 and 62.22 % of the total entrapped drug
      for 75:25 and 50:50 drug-loaded NPs, respectively. Finally, it was found that Dox
      was an appropriate anticancer agent with good capability to be encapsulated in
      polymeric NPs and could be released from the carriers with no burst effect and
      favor rate.

PMID- 22976853
TI  - Effect of low culture temperature on urokinase production in hollow fiber
      reactor.
AB  - The effect of culture temperature on urokinase production by HT-1080 cell line
      was studied in batch culture and hollow fiber reactor. Small-scale t-flask
      experiments revealed that urokinase production could be enhanced and media
      utilization could be reduced by lowering the culture temperature in production
      phase. Urokinase production was scaled up using a hollow fiber perfusion reactor
      system. Temperature of culture was maintained at the physiological 37  degrees C
      during growth phase that extended up to 12 days in hollow fiber bioreactor.
      Subsequently, in the production phase, culture temperature was lowered to 34 
      degrees C. Decrease in culture temperature resulted in a significant increase in
      urokinase production. Proteolytic degradation and inhibition was also minimized.
      The medium utilization rate was decreased at lower temperature, and hence, a
      higher economy of production could be obtained.

PMID- 22976854
TI  - Value of pilots and the need to choose the right comparator.

PMID- 22976855
TI  - Accreditation in transoesophageal echocardiography in the UK: the initial
      experience.

PMID- 22976856
TI  - Critical care echocardiography: cleared for take up.

PMID- 22976857
TI  - Ventilation strategies in obese patients undergoing surgery: a quantitative
      systematic review and meta-analysis.
AB  - BACKGROUND: Pathophysiological changes due to obesity may complicate mechanical
      ventilation during general anaesthesia. The ideal ventilation strategy is
      expected to optimize gas exchange and pulmonary mechanics and to reduce the risk
      of respiratory complications. METHODS: Systematic search (databases,
      bibliographies, to March 2012, all languages) was performed for randomized trials
      testing intraoperative ventilation strategies in obese patients (BMI >= 30 kg m(
      2)), and reporting on gas exchange, pulmonary mechanics, or pulmonary
      complications. Meta-analyses were performed when data from at least three studies
      or 100 patients could be combined. RESULTS: Thirteen studies (505 obese surgical
      patients) reported on a variety of ventilation strategies: pressure- or volume
      controlled ventilation (PCV, VCV), various tidal volumes, and different PEEP or
      recruitment manoeuvres (RM), and combinations thereof. Definitions and reporting
      of endpoints were inconsistent. In five trials (182 patients), RM added to PEEP
      compared with PEEP alone improved intraoperative PaO2/FIO2 ratio [weighted mean
      difference (WMD), 16.2 kPa; 95% confidence interval (CI), 8.0-24.4] and increased
      respiratory system compliance (WMD, 14 ml cm H(2)O(-1); 95% CI, 8-20). Arterial
      pressure remained unchanged. In four trials (100 patients) comparing PCV with
      VCV, there was no difference in PaO2/FIO2 ratio, tidal volume, or arterial
      pressure. Comparison of further ventilation strategies or combination of other
      outcomes was not feasible. Data on postoperative complications were seldom
      reported. CONCLUSIONS: The ideal intraoperative ventilation strategy in obese
      patients remains obscure. There is some evidence that RM added to PEEP compared
      with PEEP alone improves intraoperative oxygenation and compliance without
      adverse effects. There is no evidence of any difference between PCV and VCV.

PMID- 22976858
TI  - Inherited cardiomyopathies.

PMID- 22976860
TI  - FIO2 and studies on oxygenation during one-lung ventilation.

PMID- 22976862
TI  - Ultrasound-guided pulsed radiofrequency treatment of myofascial pain syndrome: a
      case series.

PMID- 22976863
TI  - Sugammadex in rocuronium anaphylaxis: dose matters.

PMID- 22976864
TI  - Clinical evaluation of the C-MAC D-Blade videolaryngoscope in severely obese
      patients: a pilot study.

PMID- 22976865
TI  - Portable Diamedica Glostavent: an anaesthetic machine for the itinerant
      anaesthetist.

PMID- 22976866
TI  - Spinal cord stimulator and epidural haematoma.

PMID- 22976867
TI  - Use of retromolar intubation in paediatric maxillofacial trauma.

PMID- 22976874
TI  - Isolated tenosynovitis of the extensor carpi radialis brevis and longus tendons
      in the second dorsal compartment of the wrist.

PMID- 22976875
TI  - The management of cyanoacrylate glue adhesions of the hand with acetone.

PMID- 22976876
TI  - In-vivo confirmation of the use of the dart thrower's motion during activities of
      daily living.
AB  - The dart thrower's motion is a wrist rotation along an oblique plane from radial
      extension to ulnar flexion. We report an in-vivo study to confirm the use of the
      dart thrower's motion during activities of daily living. Global wrist motion in
      ten volunteers was recorded using a three-dimensional optoelectronic motion
      capture system, in which digital infra-red cameras track the movement of retro
      reflective marker clusters. Global wrist motion has been approximated to the dart
      thrower's motion when hammering a nail, throwing a ball, drinking from a glass,
      pouring from a jug and twisting the lid of a jar, but not when combing hair or
      manipulating buttons. The dart thrower's motion is the plane of global wrist
      motion used during most activities of daily living. Arthrodesis of the
      radiocarpal joint instead of the midcarpal joint will allow better wrist function
      during most activities of daily living by preserving the dart thrower's motion. 

PMID- 22976877
TI  - Left and right ventricular strain and strain rate measurement in normal adults
      using velocity vector imaging: an assessment of reference values and intersystem
      agreement.
AB  - Velocity vector imaging (VVI) software permits quantitative assessment of
      ventricular function through measurement of myocardial strain (S) and strain rate
      (SR). The purpose of this study was to define a reference range of ventricular S
      and SR values in normal adults using VVI software, and to describe the
      variability among observers and systems. Two-dimensional echocardiography was
      performed in 186 healthy adults free of cardiovascular disease or risk factors,
      followed by comprehensive ventricular S and SR analysis using VVI software.
      Images were acquired using three commercial ultrasound systems. The mean age of
      patients was 44 +/- 16 years, and 114 (61 %) were female. Mean global left
      ventricular (LV) longitudinal, circumferential, and radial S and SR, and right
      ventricular (RV) longitudinal S and SR values are presented. Significant
      segmental variation in regional LV and RV S and SR was detected. Multivariate
      regression analysis demonstrated global longitudinal LV (p = 0.05) and RV (p =
      0.002) S values decline significantly with age. The overall variability of S and
      SR values accounted for by patient demographic and hemodynamic variables was low
      (16 and 8 % for LV longitudinal S and SR, respectively). Interobserver agreement
      was very good, but was lowest for LV radial S and SR. There were no significant
      differences of LV and RV S and SR between ultrasound systems. Comprehensive
      reference values for the normal ranges of LV and RV S and SR measured using VVI
      software are presented. The ultrasound system used for image acquisition did not
      significantly influence results.

PMID- 22976878
TI  - Computerized left ventricular regional ejection fraction analysis for detection
      of ischemic coronary artery disease with multidetector CT angiography.
AB  - Regional ejection fraction (REF) provides important functional information of the
      left ventricular regional myocardium. We aimed to test the diagnostic accuracy of
      computerized REF analysis for detecting the ischemia and significant stenosis
      with multidetector CT angiography (MDCT). This is a retrospective study including
      155 patients who underwent MDCT scans for evaluation of coronary artery disease.
      Among them, 83 patients also underwent SPECT imaging and invasive coronary
      angiography (ICA). Two groups of patients were defined: Control group with 0
      coronary artery calcium and normal global and regional ventricular function, and
      comparison group. REF measurement was performed on all patients using
      computerized software. Control group REF measurements will be used as reference
      standard (mean-2SD REF/mean global ejection fraction) to define abnormal REF. The
      sensitivity, specificity, positive and negative predictive value of REF in
      detecting perfusion defects (fixed and reversible) was 73, 80, 75 and 79 %
      respectively, in a patient based analysis of comparison group. The diagnostic
      accuracy of REF in predicting significant stenosis (>50 %) on ICA compared with
      SPECT was 72 versus 61 % and 85 versus 79 % in patient and vessel based analysis
      of comparison group, respectively. ROC curve analysis showed REF to be a better
      predictor of perfusion defects on SPECT compared with significant stenosis (>50
      %) alone or stenosis combined with REF (P < 0.05). The computerized assessment of
      REF analysis is comparable to SPECT in predicting ischemia and a better predictor
      of significant stenosis than SPECT. This study also provides reference standard
      to define abnormal values.

PMID- 22976879
TI  - Automated diffraction tomography for the structure elucidation of twinned, sub
      micrometer crystals of a highly porous, catalytically active bismuth metal
      organic framework.

PMID- 22976880
TI  - Does a medical home mediate racial disparities in unmet healthcare needs among
      children with special healthcare needs?
AB  - This study extends mediation analysis techniques to explore whether and to what
      extent differential access to a medical home explains the black/white disparity
      in unmet healthcare needs among children with special healthcare needs (CSHCN).
      Data were obtained from the 2007 National Survey of Children's Health, with
      analyses limited to non-Hispanic white and black CSHCN (n = 14,677). The
      counterfactual approach to mediation analysis was used to estimate odds ratios
      for the natural direct and indirect effects of race on unmet healthcare needs.
      Overall, 43.0 % of white CSHCN and 60.4 % of black CSHCN did not have a medical
      home. Additionally, 8.8 % of white CSHCN and 15.3 % of black CSHCN had unmet
      healthcare needs. The natural indirect effect indicates that the odds of unmet
      needs among black CSHCN are elevated by approximately 20 % as a result of their
      current level of access to the medical home rather than access at a level equal
      to white CSHCN (OR(NIE) = 1.2, 95 % CI = 1.1, 1.3). The natural direct effect
      indicates that even if black CSHCN had the same level of access to a medical home
      as white CSHCN, blacks would still have 60 % higher odds of unmet healthcare
      needs than whites (OR(NDE) = 1.6, 95 % CI = 1.1, 2.4). The racial disparity in
      unmet healthcare needs among CSHCN is only partially explained by disparities in
      having a medical home. Ensuring all CSHCN have equal access to a medical home may
      reduce the racial disparity in unmet needs, but will not completely eliminate it.

PMID- 22976881
TI  - Being macrosomic at birth is an independent predictor of overweight in children:
      results from the IDEFICS study.
AB  - Fetal macrosomia is a risk factor for the development of obesity late in
      childhood. We retrospectively evaluated the relationship between maternal
      conditions associated with fetal macrosomia and actual overweight/obesity in the
      European cohort of children participating in the IDEFICS study. Anthropometric
      variables, blood pressure and plasma lipids and glucose were measured. Socio
      demographic data, medical history and perinatal factors, familiar and gestational
      history, maternal and/or gestational diabetes were assessed by a questionnaire.
      Variables of interest were reported for 10,468 children (M/F = 5,294/5,174; age
      6.0 +/- 1.8 years, M +/- SD). The sample was divided in four groups according to
      child birth weight (BW) and maternal diabetes: (1) adequate for gestational age
      offspring (BW between the 10th and 90th percentiles for gestational age) of
      mothers without diabetes (AGA-ND); (2) adequate for gestational age offspring of
      mothers with diabetes (AGA-D); (3) macrosomic offspring (BW > 90th percentile for
      gestational age) of mothers without diabetes (Macro-ND); (4) macrosomic offspring
      of mothers with diabetes (Macro-D). Children macrosomic at birth showed
      significantly higher actual values of body mass index, waist circumference, and
      sum of skinfold thickness. In both boys and girls, Macro-ND was an independent
      determinant of overweight/obesity, after the adjustment for confounders [Boys: OR
      = 1.7 95 % CI (1.3;2.2); Girls: OR = 1.6 95 % CI (1.3;2.0)], while Macro-D showed
      a significant association only in girls [OR = 2.6 95 % CI (1.1;6.4)]. Fetal
      macrosomia, also in the absence of maternal/gestational diabetes, is
      independently associated with the development of overweight/obesity during
      childhood. Improving the understanding of fetal programming will contribute to
      the early prevention of childhood overweight/obesity. 

PMID- 22976882
TI  - False recognition of objects in visual scenes: findings from a combined direct
      and indirect memory test.
AB  - We report an extension of the procedure devised by Weinstein and Shanks (Memory &
      Cognition 36:1415-1428, 2008) to study false recognition and priming of pictures.
      Participants viewed scenes with multiple embedded objects (seen items), then
      studied the names of these objects and the names of other objects (read items).
      Finally, participants completed a combined direct (recognition) and indirect
      (identification) memory test that included seen items, read items, and new items.
      In the direct test, participants recognized pictures of seen and read items more
      often than new pictures. In the indirect test, participants' speed at identifying
      those same pictures was improved for pictures that they had actually studied, and
      also for falsely recognized pictures whose names they had read. These data
      provide new evidence that a false-memory induction procedure can elicit memory
      like representations that are difficult to distinguish from "true" memories of
      studied pictures.

PMID- 22976883
TI  - When disfluency is--and is not--a desirable difficulty: the influence of typeface
      clarity on metacognitive judgments and memory.
AB  - There are many instances in which perceptual disfluency leads to improved memory
      performance, a phenomenon often referred to as the perceptual-interference effect
      (e.g., Diemand-Yauman, Oppenheimer, & Vaughn (Cognition 118:111-115, 2010);
      Nairne (Journal of Experimental Psychology: Learning, Memory, and Cognition
      14:248-255, 1988)). In some situations, however, perceptual disfluency does not
      affect memory (Rhodes & Castel (Journal of Experimental Psychology: General
      137:615-625, 2008)), or even impairs memory (Glass, (Psychology and Aging 22:233
      238, 2007)). Because of the uncertain effects of perceptual disfluency, it is
      important to establish when disfluency is a "desirable difficulty" (Bjork, 1994)
      and when it is not, and the degree to which people's judgments of learning (JOLs)
      reflect the consequences of processing disfluent information. In five
      experiments, our participants saw multiple lists of blurred and clear words and
      gave JOLs after each word. The JOLs were consistently higher for the perceptually
      fluent items in within-subjects designs, which accurately predicted the pattern
      of recall performance when the presentation time was short (Exps. 1a and 2a).
      When the final test was recognition or when the presentation time was long,
      however, we found no difference in recall for clear and blurred words, although
      JOLs continued to be higher for clear words (Exps. 2b and 3). When fluency was
      manipulated between subjects, neither JOLs nor recall varied between formats
      (Exp. 1b). This study suggests a boundary condition for the desirable difficulty
      of perceptual disfluency and indicates that a visual distortion, such as blurring
      a word, may not always induce the deeper processing necessary to create a
      perceptual-interference effect.

PMID- 22976884
TI  - A pediatric translational perspective on the entity "progressive transformation
      of germinal centers (PTGC)".

PMID- 22976885
TI  - Morphine exposure induces age-dependent alterations in pentylenetetrazole-induced
      epileptic behaviors in prepubertal rats.
AB  - Opioids show both pro- and anti-epileptogenic effects in different experimental
      models of epilepsy. In the present study, the pentylentetrazole (PTZ)-induced
      seizure model was used to test the hypothesis that neonatal morphine
      administration affects seizure susceptibility in prepubertal rats. Female rats
      were subcutaneously injected with either morphine or saline on postnatal days 8
      14 (P8-P14). To verify the long-term effect of morphine (or saline), the animals
      were treated second time with morphine (21 mg/kg; or saline) on either P25 or
      P32. Morphine administration decreased latency of myoclonic jerks and time to
      onset and increased tonic-clonic seizure rate at P25, but these findings were
      inversed at P32. Results showed a significant age difference in seizure behaviors
      between P25 and P32 animals. Blood corticosterone (COS) levels were significantly
      higher in P32 rats than in P25 rats. These findings show that neonatal morphine
      exposure plays an important role in increasing seizure vulnerability in P25
      prepubertal rats but not in P32 rats. We conclude that early exposure to chronic
      morphine in infant rats might change their susceptibility to PTZ-induced seizure
      in an age-dependent manner.

PMID- 22976886
TI  - The effect of pulsed magnetic field on the molecular uptake and medium
      conductivity of leukemia cell.
AB  - The cell membrane acts as a barrier that hinders free entrance of most
      hydrophilic molecules into the cell. Owing to the numerous applications, the
      introduction of non-permeate molecules into biologic cells has drawn considerable
      attention in the past years. The aim of our study was to investigate the effect
      of time-varying magnetic field on transmembrane molecular transport by measuring
      bleomycin cytotoxicity and conductivity modifying in K562 cells. The cells were
      exposed to magnetic pulses of 2.2 T strength peak and about 250-MUs duration via
      Magstim stimulator and double 70-mm coil. Three different frequencies of 0.25, 1,
      and 10 Hz pulses for 56,112, and 28 numbers of pulses, respectively, were applied
      (nine experimental groups) and uptake and conductivity was measured in each
      group. Our results show that time-varying magnetic field increase transmembrane
      molecular transport and media conductivity; this enhancement is greater for 28
      pulses with 1 Hz frequency. The observed uptake enhancement due to magnetic
      exposure is considerable.

PMID- 22976887
TI  - Skin autofluorescence as a marker of cardiovascular risk in children with chronic
      kidney disease.
AB  - BACKGROUND: We examined skin autofluorescence (sAF) in chronic kidney disease
      children (CKD) in relation to renal function and dialysis modality. METHODS:
      Twenty children on hemodialysis (HD), 20 on peritoneal dialysis (PD), 36 treated
      conservatively, and 26 healthy subjects were enrolled into the study. In all
      children sAF, pulse-wave velocity indexed to height (PWV/ht), left ventricular
      mass index (LVMI), blood pressure (BP), serum lipid profile, phosphate (P),
      calcium (Ca), and homocysteine were measured. RESULTS: sAF was significantly
      elevated in CKD groups vs. controls and was significantly associated with PWV/ht,
      LVMI, BP, P, Ca * P product and homocysteine. sAF in HD and PD groups was
      positively correlated with dialysis vintage, and in the predialysis group
      negatively correlated with glomerular filtration rate (eGFR). Multiple regression
      analysis showed significant association of sAF with LVMI and P in the CKD patient
      group, and with dialysis treatment duration and BP in dialyzed children.
      CONCLUSIONS: In CKD children, tissue accumulation of advanced glycation end
      products (AGEs) was observed. This was aggravated as eGFR declined and was
      related to early cardiovascular changes and some biochemical cardiovascular
      disease (CVD) risk markers. sAF as a non-invasive method may be a useful tool for
      identification of a clinical risk factors of cardiovascular disease in CKD
      children.

PMID- 22976888
TI  - State of the science related to nurse work environments, safe practices, and
      organizational outcomes.

PMID- 22976889
TI  - Effects of nurse staffing and nurse education on patient deaths in hospitals with
      different nurse work environments.
AB  - CONTEXT: Better hospital nurse staffing, more educated nurses, and improved nurse
      work environments have been shown to be associated with lower hospital mortality.
      Little is known about whether and under what conditions each type of investment
      works better to improve outcomes. OBJECTIVE: To determine the conditions under
      which the impact of hospital nurse staffing, nurse education, and work
      environment are associated with patient outcomes. DESIGN, SETTING, AND
      PARTICIPANTS: Outcomes of 665 hospitals in 4 large states were studied through
      linked data from hospital discharge abstracts for 1,262,120 general, orthopedic,
      and vascular surgery patients, a random sample of 39,038 hospital staff nurses,
      and American Hospital Association data. MAIN OUTCOME MEASURES: A 30-day inpatient
      mortality and failure-to-rescue. RESULTS: The effect of decreasing workloads by 1
      patient/nurse on deaths and failure-to-rescue is virtually nil in hospitals with
      poor work environments, but decreases the odds on both deaths and failures in
      hospitals with average environments by 4%, and in hospitals with the best
      environments by 9% and 10%, respectively. The effect of 10% more Bachelors of
      Science in Nursing Degree nurses decreases the odds on both outcomes in all
      hospitals, regardless of their work environment, by roughly 4%. CONCLUSIONS:
      Although the positive effect of increasing percentages of Bachelors of Science in
      Nursing Degree nurses is consistent across all hospitals, lowering the patient-to
      nurse ratios markedly improves patient outcomes in hospitals with good work
      environments, slightly improves them in hospitals with average environments, and
      has no effect in hospitals with poor environments.

PMID- 22976890
TI  - Work environment factors other than staffing associated with nurses' ratings of
      patient care quality.
AB  - BACKGROUND: The impact of registered nurse (RN) staffing on patient care quality
      has been extensively studied. Identifying additional modifiable work environment
      factors linked to patient care quality is critical as the projected shortage of
      approximately 250,000 RNs over the next 15 years will limit institutions' ability
      to rely on RN staffing alone to ensure high-quality care. PURPOSE: We examined
      the association between RNs' ratings of patient care quality and several novel
      work environment factors adjusting for the effects of two staffing variables:
      reported patient-to-RN ratios and ratings of staffing adequacy. METHODOLOGY: We
      used a cross-sectional, correlational design and a mailed survey to collect data
      in 2009 from a national sample of RNs (n = 1,439) in the United States. A
      multivariate logistic regression was used to analyze the data. FINDINGS: Work
      group cohesion, nurse-physician relations, procedural justice, organizational
      constraints, and physical work environment were associated with RNs' ratings of
      quality, adjusting for staffing. Furthermore, employment in a Magnet hospital and
      job satisfaction were positively related to ratings of quality, whereas
      supervisory support was not. PRACTICE IMPLICATIONS: Our evidence demonstrates the
      importance of considering RN work environment factors other than staffing when
      planning improvements in patient care quality. Health care managers can use the
      results of our study to strategically allocate resources toward work environment
      factors that have the potential to improve quality of care.

PMID- 22976891
TI  - Quality and strength of patient safety climate on medical-surgical units.
AB  - BACKGROUND: Describing the safety climate in hospitals is an important first step
      in creating work environments where safety is a priority. Yet, little is known
      about the patient safety climate on medical-surgical units. PURPOSES: Study
      purposes were to describe quality and strength of the patient safety climate on
      medical-surgical units and explore hospital and unit characteristics associated
      with this climate. METHODOLOGY: Data came from a larger organizational study to
      investigate hospital and unit characteristics associated with organizational,
      nurse, and patient outcomes. The sample for this study was 3,689 RNs on 286
      medical-surgical units in 146 hospitals. FINDINGS: Nursing workgroup and
      managerial commitment to safety were the two most strongly positive attributes of
      the patient safety climate. However, issues surrounding the balance between job
      duties and safety compliance and nurses' reluctance to reveal errors continue to
      be problematic. Nurses in Magnet hospitals were more likely to communicate about
      errors and participate in error-related problem solving. Nurses on smaller units
      and units with lower work complexity reported greater safety compliance and were
      more likely to communicate about and reveal errors. Nurses on smaller units also
      reported greater commitment to patient safety and participation in error-related
      problem solving. PRACTICE IMPLICATIONS: Nursing workgroup commitment to safety is
      a valuable resource that can be leveraged to promote a sense of personal
      responsibility for and shared ownership of patient safety. Managers can
      capitalize on this commitment by promoting a work environment in which control
      over nursing practice and active participation in unit decisions are encouraged
      and by developing channels of communication that increase staff nurse involvement
      in identifying patient safety issues, prioritizing unit-level safety goals, and
      resolving day-to-day operational problems the have the potential to jeopardize
      patient safety.

PMID- 22976892
TI  - Transformational leadership practices of chief nursing officers in Magnet(r)
      organizations.
AB  - OBJECTIVE: This study describes the transformational leadership practices of
      Magnet(r) chief nursing officers (CNOs). BACKGROUND: It is believed that
      transformational leadership practices influence quality and are integral to
      Magnet designation. METHODS: E-mail surveys of 384 Magnet CNOs were conducted in
      2011 using the leadership practices inventory (LPI). RESULTS: Enabling others to
      act and modeling the way are top practices of Magnet CNOs. Those 60 years or
      older and those with doctorate degrees scored significantly higher in inspiring a
      shared vision and challenging the process. There was a significant positive
      relationship between total years as a CNO and inspiring a shared vision and
      between total scores on the LPI and number of beds in the organization.
      CONCLUSIONS: As CNOs gain experience and education, they exhibit more
      transformational leadership characteristics. Magnet organizations should take
      steps to retain CNOs and support their development and advancement.

PMID- 22976893
TI  - Adoption of national quality forum safe practices by Magnet(r) hospitals.
AB  - BACKGROUND: Magnet(r) hospitals (MHs) are known for their high retention rates of
      nurses and positive work environment, yet little is known about whether MHs also
      have higher levels of safe practice adoption rates compared with non-Magnet
      hospitals (NMHs). METHODS: In this study, we investigate adoption of National
      Quality Forum (NQF) Safe Practices in 34 regions during 2004 to 2006 that were
      part of the Leapfrog Group initiative to improve quality of hospital care. We
      conducted a secondary data analysis by combining multiple data sets from the
      American Hospital Association Annual Survey,Healthcare Cost Reports Information
      System, and Leapfrog Group Annual Hospital Survey. A composite safe practice
      score (CSPS) was constructed from the Leapfrog annual survey and ranged from 0
      (no adoption) to 1,000 (complete adoption) of the 30 NQF Safe Practices. A
      descriptive analysis and a regression with Heckman correction to control for
      selection bias were used to determine the effect of Magnet status and other
      hospital and market characteristics on differences in CSPS over the 3-year
      period. RESULTS: There were 140 MHs and 1,320 NMHs reporting data for the CSPS.
      In 2004, MHs had a mean CSPS of 865 versus 774 for NMHs (P < .001). By 2006, NMHs
      improved their CSPS from 774 to 872 (98 points), whereas MHs improved their CSPS
      from 865 to 925 (60 points, P < .001). Regression analysis showed a positive and
      significant effect of Magnet status of hospitals on the adoption rates of NQF
      Safe Practices as measured by the CSPS. Our results also indicated that smaller
      hospitals (in bed size), hospitals with larger share of Medicare patients, higher
      nurse intensity levels (mean hours of nursing care per day), and higher levels of
      competition among hospitals in Leapfrog rollout regions were associated with
      higher CSPS. CONCLUSION: Magnet hospitals in the urban areas of 34 Leapfrog
      rollout regions were more likely to have higher adoption rates of NQF Safe
      Practices in comparison to NMHs in the same demographic areas during the time
      frame of the study, but other hospitals nearly closed the gap by 2006.

PMID- 22976894
TI  - Nurse outcomes in Magnet(r) and non-Magnet hospitals.
AB  - The important goals of Magnet(r) hospitals are to create supportive professional
      nursing care environments. A recently published paper found little difference in
      work environments between Magnet and non-Magnet hospitals. The aim of this study
      was to determine whether work environments, staffing, and nurse outcomes differ
      between Magnet and non-Magnet hospitals. A secondary analysis of data from a 4
      state survey of 26,276 nurses in 567 acute care hospitals to evaluate differences
      in work environments and nurse outcomes in Magnet and non-Magnet hospitals was
      conducted. Magnet hospitals had significantly better work environments (t = 
      5.29, P < .001) and more highly educated nurses (t = -2.27, P < .001). Magnet
      hospital nurses were 18% less likely to be dissatisfied with their job (P < .05)
      and 13% less likely to report high burnout (P < .05). Magnet hospitals have
      significantly better work environments than non-Magnet hospitals. The better work
      environments of Magnet hospitals are associated with lower levels of nurse job
      dissatisfaction and burnout.

PMID- 22976895
TI  - Employer-provided support services and job dissatisfaction in Canadian registered
      nurses.
AB  - BACKGROUND: Previous research indicates that nurses' job dissatisfaction relates
      to their work organization and environment; rarely has the contribution of
      employer provided support services been examined while controlling for the
      influence of other factors. OBJECTIVE: The objective of this study was to examine
      job dissatisfaction among Canadian registered nurses in relation to employer
      provided programs for child care and fitness or recreation. METHODS: Data are
      from 2,993 respondents to the 2005 National Survey of the Work and Health of
      Nurses, weighted to represent Canada's 91,600 registered nurses in full-time,
      permanent positions who deliver direct care in hospitals or long-term care
      facilities. Multivariate modeling was used to examine job dissatisfaction in
      relation to employer-provided support programs, controlling for personal
      characteristics and variables reflecting work organization and the work
      environment. RESULTS: Employer-provided child care assistance programs were
      available to 16% of nurses, and fitness or recreation programs were available to
      38%. An estimated 13% of nurses were dissatisfied with their jobs. Even when
      controlling for personal characteristics, overtime, shift work, shift length,
      weekly hours, overload, staffing inadequacy, autonomy, nurse-physician relations,
      and coworker respect, inverse associations with job dissatisfaction emerged for
      employer-supported child care (odds ratio = 0.49, 95% confidence interval = 0.27
      0.88) and fitness programs (odds ratio = 0.65, 95% confidence interval = 0.42
      0.99). DISCUSSION: This study provides new information suggesting that employer
      provided support programs are protective against nurses' job dissatisfaction.
      This is a key finding in view of nursing shortages and the importance of job
      satisfaction to retention.

PMID- 22976896
TI  - The future of the h-index: can bending an already non-linear metric work?

PMID- 22976900
TI  - Valuable new cyclohexadiene building blocks from cationic eta5-iron-carbonyl
      complexes derived from a microbial arene oxidation product.
AB  - Biooxidation of benzoic acid by Ralstonia eutropha B9 provides an unusual
      cyclohexadiene carboxy diol that contains a quaternary stereocentre.
      Tricarbonyliron derivatives of this chiron, on treatment with acid, give two
      isomeric eta(5)-cyclohexadienyl complexes as observed by NMR spectroscopy. Both
      of these can be subjected to the addition of nucleophiles to provide isomeric
      cyclohexadiene complexes with new substituent patterns, several of which have
      been characterised crystallographically. De-metallation of these provides a
      versatile library of cyclohexadiene building blocks, the utility of which is
      demonstrated by formal syntheses of oseltamivir. The mechanism of product
      formation and its stereochemical implications are discussed, as are the
      procedures undertaken to establish the enantiopurity of a representative
      cyclohexadiene product.

PMID- 22976901
TI  - Guanosine triphosphate cyclohydrolase 1 promoter deletion causes dopa-responsive
      dystonia.
AB  - BACKGROUND: Autosomal dominant dopa-responsive dystonia (AD-DRD) is caused by a
      biochemical defect primarily resulting from guanosine triphosphate cyclohydrolase
      1 gene (GCH1) mutations. Few families have been reported without mutations in
      GCH1. METHODS: Genome-wide linkage analysis and positional cloning to identify
      the genetic defect in a Belgian AD-DRD family was carried out. RESULTS AND
      CONCLUSION: In this study, we report on the identification and characterization
      of a novel 24-kb deletion spanning exon 1 and the 5' regulatory region of GCH1
      causing a wide spectrum of motor and nonmotor symptoms in a large Belgian AD-DRD
      family. This large-scale deletion of regulatory sequences leads to decreased GCH1
      activity in all carriers, most probably resulting from allelic loss of
      transcription. We mapped the breakpoints of this deletion to the nucleotide
      level, allowing the development of a straightforward polymerase chain reaction
      assay for fast, efficient detection of this large deletion, which will prove
      valuable for preimplantation genetic diagnosis.

PMID- 22976902
TI  - Gold-catalyzed functionalization of unactivated C(sp3)-H bonds by hydride
      transfer facilitated by alkynylspirocyclopropanes.

PMID- 22976903
TI  - Dynamic changes in nuclear localization of a DNA-binding protein tyrosine
      phosphatase TCPTP in response to DNA damage and replication arrest.
AB  - TCPTP is an ubiquitously expressed tyrosine phosphatase with a predominant
      nuclear isoform (TC45) that binds DNA and has a role in G1-S cell cycle
      progression. Its deregulation by overexpression induces p53-dependent apoptosis,
      but the physiological role of its DNA-binding function is not known. Using
      immunocytochemistry and subcellular fractionation, we investigated changes in its
      localization in response to DNA damage and replication arrest. Rat fibroblasts
      showed an increase in endogenous TCPTP bound to nuclear components 3 h after
      exposure to sublethal dose of UV irradiation. Fractionation of nuclei showed an
      increase in chromatin and nuclear matrix associated component of TC45. After UV
      treatment, cells showed a concentration of TCPTP in discrete foci and enhanced
      colocalization with PCNA and p53BP1. Cells arrested at G1-S transition by
      hydroxyurea showed a loss of the predominant nuclear staining of TCPTP and an
      increase in cytoplasmic staining. Upon release from replication block, there was
      a time-dependent increase in number of cells showing prominent nuclear
      localization. This change in localization coincides with that of PCNA and Cdk2,
      two other nuclear proteins having functions in DNA replication. These results
      provide evidence for the regulation of TCPTP in response to DNA damage and
      replication stress. Dynamic changes in its localization coincident with that of
      PCNA suggest involvement of TCPTP in DNA repair and replication.

PMID- 22976905
TI  - Onychomycosis due to Neoscytalidium treated with oral terbinafine, ciclopirox
      nail lacquer and nail abrasion: a pilot study of 25 patients.
AB  - BACKGROUND: Onychomycosis by Neoscytalidium constitutes chronic infection of the
      nails, and its frequency has increased in recent decades. Currently, no effective
      standard treatment exists and literature data remain scarce. This work aimed to
      conduct a pilot project of combined treatment for this infection. METHODS: Thirty
      patients were divided into three treatment groups: oral terbinafine plus
      ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and
      ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when
      required, for 12 months, with 6 months posttreatment follow-up. Clinical and
      mycological criteria were used for evaluation. RESULTS: Twenty-five patients
      completed the study. Significant clinical lesion reduction in disease occurred in
      all three treatment groups: 21 patients (84%) entered the study with more than
      50% of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84
      and 96%, respectively, presented less than 25% nail lesion. Negative microscopy
      was observed in 36% of the patients at the end of treatment and in 24% of the
      patients at 6-month follow-up. At treatment completion (12 months), culture was
      negative in 21 patients (84%) and in 18 (72%) at follow-up. It was not possible
      to establish any clinical or mycological statistical differences between groups
      (p > 0.05). Global medical evaluation upon treatment completion revealed that one
      patient (4%) presented complete cure, 8 (32%) presented partial cure, 16 (64%)
      presented therapeutic failure. At the end of follow-up period, 6 patients (24%)
      were considered to have recurrence/reinfection. CONCLUSIONS: The results obtained
      at the 6-month period of follow-up showed marked improvement (96% of clinical
      improvement and 72% of negative culture) of the patients treated for
      onychomycosis caused by Neoscytalidium in the three tested groups with no
      statistical differences between them. Multicentric studies with greater number of
      patients enrolled are necessary to confirm these results.

PMID- 22976904
TI  - Correlates of reasons for not reporting rape to police: results from a national
      telephone household probability sample of women with forcible or drug-or-alcohol
      facilitated/incapacitated rape.
AB  - Rape tactics, rape incident characteristics, and mental health problems (lifetime
      depression, PTSD, and substance abuse) were investigated as correlates of eight
      different reasons for not reporting a rape to police among women who had
      experienced but did not report a rape to police (n = 441) within a national
      telephone household probability sample. Rape tactics (nonmutually exclusive)
      included drug or alcohol-facilitated or incapacitated rape (DAFR/IR; n = 119) and
      forcible rape (FR; n = 376). Principal Components Analysis (PCA) was conducted to
      extract a dominant set of patterns among the eight reasons for not reporting, and
      to reduce the set of dependent variables. PCA results indicated three unique
      factors: Not Wanting Others to Know, Nonacknowledgment of Rape, and Criminal
      Justice Concerns. Hierarchical regression analyses showed DAFR/IR and FR were
      both positively and significantly associated with Criminal Justice Concerns,
      whereas DAFR/IR, but not FR, was associated with Nonacknowledgment as a reason
      for not reporting to police. Neither DAFR/IR nor FR emerged as significant
      predictors of Others Knowing after controlling for fear of death or injury at the
      time of the incident. Correlations among variables showed that the Criminal
      Justice Concerns factor was positively related to lifetime depression and PTSD
      and the Nonacknowledgement factor was negatively related to lifetime PTSD.
      Findings suggest prevention programs should educate women about the definition of
      rape, which may include incapacitation due to alcohol or drugs, to increase
      acknowledgement and decrease barriers to police reporting.

PMID- 22976906
TI  - FIFA Women's World Cup 2011: pre-competition medical assessment of female
      referees and assistant referees.
AB  - BACKGROUND: Precompetition screening was implemented for male referees during the
      2010 Federation Internationale de Football Association (FIFA) Word Cup. In
      contrast, female football referees have been neglected in this respect although
      they experience similar physical work loads compared to male referees. METHODS:
      The standardised football-specific pre-competition medical assessment (PCMA) was
      performed in 51 referees and assistant referees selected for the 2011 FIFA
      Women's World Cup. RESULTS: Family history for sudden cardiac death (SCD) was
      positive in four referees (7.8%), but cardiac examinations did not reveal any
      pathological findings. Training-unrelated ECG changes were identified in three
      referees (5.9%), all without correlates in echocardiography or clinical
      examination. Most common echocardiography findings (66.6%, n=34) were
      asymptomatic tricuspid and mitral regurgitations. CONCLUSIONS: During the present
      screening, no elite female referee was identified being at risk for SCD, and no
      referee had to be excluded from participating in the 2011 FIFA Women's World Cup.

PMID- 22976907
TI  - The role of a relative age effect in the first winter Youth Olympic Games in
      2012.
AB  - BACKGROUND: Owing to the separation into age groups at the first winter Youth
      Olympic Games (YOG), athletes differed in age by up to two years, leading to a
      potential relative age effect (RAE). OBJECTIVE: The purpose of this study was to
      define the role of the RAE in the first winter YOG with regard to sex, type of
      sport and performance. METHODS: The birth dates and anthropometric data of all
      1021 athletes (557 male, 464 female, 14-19 years old) participating in 15 sports
      were analysed. A chi(2) test was used to assess the difference between the
      observed and expected birth distributions. ANOVA (analysis of variance) and
      Kruskal-Wallis analyses were used to investigate differences in anthropometrics.
      RESULTS: The birth date distribution of the overall sample was significantly
      different from an equal distribution, with an over-representation of athletes
      born shortly after the cut-off date (chi(2)=284.7, p<0.001). A significant RAE
      was found in both male (chi(2)=245.1, p<0.001) and female competitors
      (chi(2)=74.6, p<0.001). An analysis based on the type of sport showed an RAE in
      all categories (strength-chi(2)=229.9, p<0.001, endurance-chi(2)=60.4, p<0.001
      and technique-related sports chi(2)=25.2, p=0.001). Relatively older competitors
      were also over-represented among medal winners (chi(2)=47.9, p<0.001). Relatively
      older male competitors were significantly taller (p=0.005) and heavier (p<0.001)
      than younger competitors. No differences were found in female competitors.
      CONCLUSIONS: The results suggest that relative age had a highly significant
      influence on participation in various sports regardless of sex. A possible
      strategy to reduce the RAE would be a fixed quota for each birth year within the
      two-year age group across events.

PMID- 22976908
TI  - Do helmets worn for hurling fail to protect the ear? Identification of an
      emerging injury pattern.
AB  - Hurling is an Irish national game of stick and ball known for its ferocity,
      played by 190 000 players. Facial injuries were common but have been
      significantly reduced by legislation enforcing compulsory helmet wearing. Current
      standard helmets worn by hurlers do not offer protection to the external ear.
      Here we describe an emerging pattern of ear injuries and demonstrate the risk of
      external ear injuries in hurlers complying with current helmet safety standards.
      A 6-month retrospective analysis was carried out of patients attending Cork
      University Hospital (CUH) with ear lacerations sustained while hurling. Patient
      notes were reviewed and helmet manufacturers were interviewed. Seven patients
      were identified, all of whom sustained complex through ear lacerations while
      wearing helmets complying with current safety standards. Current helmet design
      fails to protect the external ear placing it at an increased risk of injury, a
      potential solution is to include ear protection in the helmet design.

PMID- 22976909
TI  - Neuromuscular training strategies for preventing lower limb injuries: what's new
      and what are the practical implications of what we already know?

PMID- 22976911
TI  - Concussion tests: clarifying potential confusion regarding sideline assessment
      and cognitive testing.

PMID- 22976910
TI  - 'Sedentary behaviour counselling': the next step in lifestyle counselling in
      primary care; pilot findings from the Rapid Assessment Disuse Index (RADI) study.
AB  - BACKGROUND: Accumulating evidence emphasises a relationship between prolonged
      sitting and increased risk for cardiometabolic disorders and premature death
      irrespective of the protective effects of physical activity. Primary care
      physicians have the potential to play a key role in modifying patients' sedentary
      behaviour alongside physical activity. METHODS: A pilot study examining sedentary
      behaviour and physical activity counselling in a primary care clinic. A total of
      157 patients completed a detailed survey related to lifestyle counselling
      received from their primary care physician. We analysed these responses to
      describe counselling practices within the 5A framework, and to examine correlates
      (ie, patients' demographics, sedentary behaviour and physical activity and
      clinical variables) related to receiving counselling. RESULTS: A total of 10%
      received general advice to decrease sitting time, in comparison with 53%
      receiving general physical activity counselling. None, however, received a
      written plan pertaining to sedentary behaviour whereas 14% received a written
      physical activity prescription. Only 2% were provided with specific strategies
      for sedentary behaviour change in comparison with 10% for physical activity
      change. Multivariable analysis revealed that patients who were obese were more
      likely to receive counselling to decrease sitting (OR=7.0; 95% CI 1.4 to 35.2).
      In comparison, higher odds for receiving physical activity counselling were
      associated with being younger, aged 40-59 years (OR=2.4; 95% CI 1.1 to 5.4); and
      being a non-smoker (OR=6.1; 95% CI 1.3 to 28.4). CONCLUSIONS: This study is the
      first to assess sedentary behaviour counselling practices in primary care and
      such practices appear to be infrequent. Future research should attempt to
      establish a 'knowledge base' to inform development of sedentary behaviour
      interventions, which should be followed by testing feasibility, efficacy, and
      subsequent effectiveness of these programmes in a clinical setting.

PMID- 22976912
TI  - Preparticipation cardiovascular screening among National Collegiate Athletic
      Association Division I institutions.
AB  - BACKGROUND: Sudden cardiac arrest is the leading cause of death in competitive
      athletes during sport, and screening strategies for the prevention of sudden
      cardiac death are debated. The purpose of this study was to assess the
      incorporation of routine non-invasive cardiovascular screening (NICS), such as
      ECG or echocardiography, in Division I collegiate preparticipation examinations.
      METHODS: Cross-sectional survey of current screening practices sent to the head
      athletic trainer of all National Collegiate Athletic Association (NCAA) Division
      I football programmes listed in the National Athletic Trainers' Association
      directory. RESULTS: Seventy-four of 116 (64%) programmes responded. Thirty-five
      of 74 (47%) of responding schools have incorporated routine NICS testing. ECG is
      the primary modality for NICS in 31 (42%) of schools, and 17 (49%) also utilise
      echocardiography. Sixty-four per cent of the programmes that do NICS routinely
      screen their athletes only once as incoming freshmen. Of institutions that do not
      conduct NICS, American Heart Association guidelines against routine NICS and cost
      were the most common reasons reported. CONCLUSIONS: While substantial debate
      exists regarding protocols for cardiovascular screening in athletes, nearly half
      of NCAA Division I football programmes in this study already incorporate NICS
      into their preparticipation screening programme. Additional research is needed to
      understand the impact of NICS in collegiate programmes.

PMID- 22976913
TI  - Gangrene from finger pricking.

PMID- 22976914
TI  - Circadian rhythm of salivary cortisol in infants with congenital heart disease.
AB  - Children with congenital heart disease (CHD) have associated extracardiac co
      morbidities at the time of surgery and during ongoing growth and development.
      Perioperative events include disrupted glucose homeostasis, capillary leak, and
      fluid retention. The hypothalamic-pituitary-adrenal (HPA) axis has an important
      role in homeostasis in that the secretion of cortisol contributes to the response
      to stress, glucose regulation, blood volume control, and immune regulation. We
      investigated the diurnal rhythm of the HPA axis in infants with CHD by measuring
      salivary cortisol in the morning (0600-0900 h-circadian peak) and evening (2100
      2400 h-circadian nadir). Twenty-nine infants aged 12 weeks to 1 year were
      included: 16 with acyanotic disease (SpO2 >= 90 %) and 13 with cyanotic disease
      (SpO2 < 90 %). Morning salivary cortisol was similar between the two groups
      [acyanotic 7.0 nmol/L (1.8-23.1); cyanotic 9.7 nmol/L (0.9-15.6); p = 0.68].
      Evening salivary cortisol was similar between the two groups [acyanotic 0.9
      nmol/L (0.2-8.5); cyanotic 1.4 nmol/L (0.5-14.9); p = 0.32]. Both cyanotic and
      acyanotic groups demonstrated an intact diurnal rhythm. In conclusion, chronic
      hypoxia secondary to cyanotic CHD does not affect the circadian rhythm of the HPA
      axis. By 12 weeks of age, infants with hypoxia secondary to cyanotic CHD have a
      normal cortisol diurnal rhythm.

PMID- 22976915
TI  - Clinical and molecular features of attenuated adenomatous polyposis in northern
      Italy.
AB  - BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is characterized by
      the presence of 10-99 colorectal adenomas. The disease may be associated with
      mutations in either APC or MUTYH genes. We purposed to evaluate the contribution
      of adenomatous polyposis coli (APC) and MutY homologue (MUTYH) germline
      alterations to the AFAP phenotype and to identify genotype/phenotype
      correlations. METHODS: During counselling for familial adenomatous polyposis
      (FAP), 91 probands (and 107 affected individuals) who met the criteria of AFAP
      were identified. Eighty-two families were screened for constitutional mutations
      of the APC and MUTYH genes. RESULTS: MUTYH mutations were detected in 21 families
      (25.6 % of the 82 tested), and APC mutations in 7 (8.5 %). Overall,
      constitutional alterations were found in 34.1 % of the probands. Patients with
      APC mutations were younger at cancer onset and had a higher mean number of polyps
      (48.5 +/- 33.0 in APC+ individuals vs. 35.7 +/- 24.9 in MUTYH+ individuals, and
      33.2 +/- 18.4 in the "no mutation" group). Clinical features rendered the "no
      mutation" group closer to MUTYH+ than to the APC+ group. Colorectal cancer at
      diagnosis was detected in 40 % of AFAP individuals. CONCLUSIONS: AFAP is a new
      clinical entity with its frequency in the general population still undefined. The
      number of adenomas varies greatly, with an average of 30-40 lesions. The
      molecular basis of AFAP can be established in approximately 1/3 of the patients.
      Both MUTYH and APC genes are implicated in AFAP, though the role of MUTYH is of
      considerably greater relevance.

PMID- 22976916
TI  - Morphological changes of the thoracic duct and accessory lymphatic channels in
      patients with chylothorax: detection with unenhanced magnetic resonance imaging.
AB  - OBJECTIVES: To characterise the imaging findings of patients with chylothorax and
      to identify the leak site using unenhanced MRI. METHODS: Seven patients with
      chylothorax and 30 healthy individuals (as the control group) underwent three
      dimensional heavily and routine T2-weighted MRI. Morphological changes and
      diameters of the thoracic duct, chyloma display, and some dilated accessory lymph
      channels were evaluated and measured. The differences between patients and the
      control group were compared. The leak sites of the thoracic duct and parietal
      pleura were also identified. RESULTS: The patients had a higher display rate of
      the entire thoracic duct and some accessory lymphatic channels, enlarged
      diameters and tortuous configuration of the thoracic duct, and existence of
      chylomas compared with the control group (P < 0.05). Seven leaks of the thoracic
      duct in five patients and five leaks of the parietal pleura in four patients were
      identified. Close relationships between the leak of thoracic duct and the
      chylomas or the meshworks of tiny lymphatics were found (P < 0.05). CONCLUSION:
      Unenhanced MRI appears reliable in the detection of morphological changes of
      thoracic lymphatics and in the identification of chyloma and leak sites in
      patients with chylothorax, which helps appropriate treatment planning and follow
      up.

PMID- 22976917
TI  - Percutaneous transthoracic needle biopsy of small (<= 1 cm) lung nodules under C
      arm cone-beam CT virtual navigation guidance.
AB  - OBJECTIVES: To describe our initial experience with percutaneous transthoracic
      needle biopsy (PCNB) of small (<=1 cm) lung nodules using a cone-beam computed
      tomography (CBCT) virtual navigation guidance system in 105 consecutive patients.
      METHODS: One hundred and five consecutive patients (55 male, 50 female; mean age,
      62 years) with 107 small (<=1 cm) lung nodules (mean size, 0.85 cm +/- 0.14)
      underwent PCNBs under CBCT virtual-navigation guidance system and constituted our
      study population. Procedural details-including radiation dose, sensitivity,
      specificity, diagnostic accuracy and complication rates of CBCT virtual
      navigation guided PCNBs-were described. RESULTS: The mean number of pleural
      passages with the coaxial needle, biopsies, CT acquisitions, total procedure
      time, coaxial introducer dwelling time, and estimated radiation exposure during
      PCNBs were 1.03 +/- 0.21, 3.1 +/- 0.7, 3.4 +/- 1.3, 10.5 min +/- 3.2 and 7.2 min
      +/- 2.5, and 5.72 mSv +/- 4.19, respectively. Sixty nodules (56.1 %) were
      diagnosed as malignant, 38 (35.5 %) as benign and nine (8.4 %) as indeterminate.
      The sensitivity, specificity, and diagnostic accuracy of CBCT virtual-navigation
      guided PCNB for small (<=1 cm) nodules were 96.7 % (58/60), 100 % (38/38) and
      98.0 % (96/98), respectively. Complications occurred in 13 (12.1 %) cases;
      pneumothorax in seven (6.5 %) and haemoptysis in six (5.6 %). CONCLUSION: CBCT
      virtual-navigation-guided PCNB is a highly accurate and safe diagnostic method
      for small (<=1 cm) nodules.

PMID- 22976918
TI  - Visually assessed colour overlay features in shear-wave elastography for breast
      masses: quantification and diagnostic performance.
AB  - OBJECTIVES: To determine whether colour overlay features can be quantified by the
      standard deviation (SD) of the elasticity measured in shear-wave elastography
      (SWE) and to evaluate the diagnostic performance for breast masses. METHODS: One
      hundred thirty-three breast lesions in 119 consecutive women who underwent SWE
      before US-guided core needle biopsy or surgical excision were analysed. SWE
      colour overlay features were assessed using two different colour overlay pattern
      classifications. Quantitative SD of the elasticity value was measured with the
      region of interest including the whole breast lesion. RESULTS: For the four
      colour overlay pattern, the area under the ROC curve (Az) was 0.947; with a
      cutoff point between pattern 2 and 3, sensitivity and specificity were 94.4 % and
      81.4 %. According to the homogeneity of the elasticity, the Az was 0.887; with a
      cutoff point between reasonably homogeneous and heterogeneous, sensitivity and
      specificity were 86.1 % and 82.5 %. For the SD of the elasticity, the Az was
      0.944; with a cutoff point of 12.1, sensitivity and specificity were 88.9 % and
      89.7 %. The colour overlay features showed significant correlations with the
      quantitative SD of the elasticity (P < 0.001). CONCLUSION: The colour overlay
      features and the SD of the elasticity in SWE showed excellent diagnostic
      performance and showed good correlations between them.

PMID- 22976919
TI  - Performance comparison of single-view digital breast tomosynthesis plus single
      view digital mammography with two-view digital mammography.
AB  - OBJECTIVE: To determine the performance of combined single-view mediolateral
      oblique (MLO) digital breast tomosynthesis (DBT) plus single-view cranio-caudal
      (CC) mammography (MX) compared with that of standard two-view digital
      mammography. METHODS: A multi-reader multi-case (MRMC) receiver-operating
      characteristic (ROC) study was conducted, involving six breast radiologists. Two
      hundred fifty patients underwent bilateral MX and DBT imaging. MX and DBT images
      with the adjunct of the CC-MX view from 469 breasts were evaluated and rated
      independently by six readers. Differences in mean areas under the ROC curves
      (AUCs), mean sensitivity and mean specificity were analysed by analysis of
      variance (ANOVA) to assess clinical performance. RESULTS: The combined technique
      was found to be non-inferior to standard two-view mammography (MX((CC+MLO))) in
      mean AUC (difference: +0.021;95 % LCL = -0.011), but was not statistically
      significant for superiority (P = 0.197). The combined technique had equivalent
      sensitivity to standard mammography (76.2 % vs. 72.8 %, P = 0.269) and equivalent
      specificity (84.9 % vs. 83.0 %, P = 0.130). Specificity for benign lesions was
      significantly higher with the combination of techniques versus mammography (45.6
      % vs. 36.8 %, P = 0.002). CONCLUSION: In this enriched study population, the
      combination of single-view MLO tomosynthesis plus single-view CC mammography was
      non-inferior to that of standard two-view digital mammography in terms of ROC
      curve area, sensitivity and specificity.

PMID- 22976920
TI  - Staging of colorectal liver metastases after preoperative chemotherapy. Diffusion
      weighted imaging in combination with Gd-EOB-DTPA MRI sequences increases
      sensitivity and diagnostic accuracy.
AB  - OBJECTIVES: To compare the diagnostic accuracy and sensitivity of Gd-EOB-DTPA MRI
      and diffusion-weighted (DWI) imaging alone and in combination for detecting
      colorectal liver metastases in patients who had undergone preoperative
      chemotherapy. METHODS: Thirty-two consecutive patients with a total of 166 liver
      lesions were retrospectively enrolled. Of the lesions, 144 (86.8 %) were
      metastatic at pathology. Three image sets (1, Gd-EOB-DTPA; 2, DWI; 3, combined Gd
      EOB-DTPA and DWI) were independently reviewed by two observers. Statistical
      analysis was performed on a per-lesion basis. RESULTS: Evaluation of image set 1
      correctly identified 127/166 lesions (accuracy 76.5 %; 95 % CI 69.3-82.7) and
      106/144 metastases (sensitivity 73.6 %, 95 % CI 65.6-80.6). Evaluation of image
      set 2 correctly identified 108/166 (accuracy 65.1 %, 95 % CI 57.3-72.3) and
      87/144 metastases (sensitivity of 60.4 %, 95 % CI 51.9-68.5). Evaluation of image
      set 3 correctly identified 148/166 (accuracy 89.2 %, 95 % CI 83.4-93.4) and
      131/144 metastases (sensitivity 91 %, 95 % CI 85.1-95.1). Differences were
      statistically significant (P < 0.001). Notably, similar results were obtained
      analysing only small lesions (<1 cm). CONCLUSIONS: The combination of DWI with Gd
      EOB-DTPA-enhanced MRI imaging significantly increases the diagnostic accuracy and
      sensitivity in patients with colorectal liver metastases treated with
      preoperative chemotherapy, and it is particularly effective in the detection of
      small lesions.

PMID- 22976922
TI  - Long-term efficacy and toxicity of bevacizumab-based therapy in children with
      recurrent low-grade gliomas.
AB  - BACKGROUND: Because definitive resection or radiotherapy for pediatric low-grade
      gliomas (LGGs) may be associated with severe and permanent adverse effects,
      medical management has taken a significant role. Bevacizumab-based therapy has
      demonstrated encouraging responses; however, longer-term toxicity, response
      durability and alternative dosing regimens have not been evaluated. PROCEDURE:
      This was a retrospective review of children with multiply recurrent, progressive
      LGGs treated with bevacizumab-based therapy and followed for at least 12 months
      after treatment completion. Toxicity was uniformly graded and imaging was
      centrally reviewed. RESULTS: All fourteen patients had failed at least two prior
      treatment regimens; six had dissemination. Patients received initial bevacizumab
      based therapy at a median age of 5.3 years (range, 1-12 years). Median treatment
      duration was 12 months (range, 1-24 months). 12 patients had an objective
      response; 2 had stable disease. Median time to maximum response was 9 weeks
      (range, 7-17 weeks). No patients progressed on therapy, although 13/14 progressed
      after stopping bevacizumab at a median of 5 months. Four patients were re-treated
      with bevacizumab and all again responded or stabilized. Alternative dosing
      strategies were effective, including bevacizumab monotherapy and prolonging the
      dosing interval to 3 weeks. High-grade bevacizumab-related toxicities consisted
      of grade 3 proteinuria (n = 2), primary inflammatory arthritis (n = 1), and
      somnolence (n = 1). Toxicities resolved within 6 months of treatment cessation
      except one case of hypertension. CONCLUSIONS: Bevacizumab-based therapy is
      successful at inducing rapid LGG response. Patients progressing off-therapy may
      be successfully re-treated with bevacizumab. Nearly all tumors progress once
      treatment is discontinued. Toxicities are not insignificant but usually
      reversible.

PMID- 22976923
TI  - Enantioselective synthesis of tetrahydrocarbazoles through a Michael
      addition/Ciamician-Plancher rearrangement sequence: asymmetric synthesis of a
      potent constrained analogue of MS-245.

PMID- 22976921
TI  - Nausea still the poor relation in antiemetic therapy? The impact on cancer
      patients' quality of life and psychological adjustment of nausea, vomiting and
      appetite loss, individually and concurrently as part of a symptom cluster.
AB  - PURPOSE: Despite significant antiemetic advances, almost 50% of treated cancer
      patients still experience nausea and vomiting (N&V). The goal of antiemetic
      therapy--complete prevention of treatment-induced nausea and/or vomiting (TIN+/
      V)--remains elusive for several reasons. Potentially, N&V may be part of a
      symptom cluster where co-occurring symptoms negatively affect antiemetic
      management. Consequently, we examined TIN+/-V incidence and the impact of nausea,
      vomiting and symptom cluster(s) containing them, respectively, on patients'
      quality of life (QoL) and psychological adjustment across treatment. METHODS: A
      longitudinal secondary analysis was performed on data from a prospective,
      observational QoL study involving 200 newly diagnosed cancer patients who
      underwent combined modality treatment. QoL, psychological adjustment and
      patient/clinical characteristics were examined at pretreatment, on-treatment (8
      weeks) and post-treatment. RESULTS: Overall, 62% of patients experienced TIN+/-V,
      with TIN (60%) doubling TIV incidence (27 %). Exploratory factor analyses of QoL
      scores at each treatment time point identified a recurrent gastrointestinal
      symptom cluster comprising nausea, vomiting and appetite loss. Approximately two
      thirds of patients reported co-occurrence of all three symptoms, which exerted
      synergistic effects of multiplicative proportions on overall QoL. Patients who
      reported co-occurrence of these symptoms during treatment experienced
      significantly greater QoL impairment (physical, role and social functioning,
      fatigue, N&V, appetite loss, overall physical health, overall QOL) and
      psychological distress (cancer distress, premorbid neuroticism) than those
      unaffected (0.001 > p <= 0.05). Moreover, nausea was more pervasive than vomiting
      or appetite loss across treatment and had a greater impact on overall QoL. While
      antiemetic therapy was effective for vomiting and helped prevent/relieve
      associated appetite loss, the benefits for appetite loss were seemingly
      constrained by its failure to exert adequate control over nausea in many
      patients. CONCLUSIONS: TIN+/-V still represents a very major concern for
      patients. Uncontrolled TIN+/-V often results in significant appetite and weight
      loss, leading to increased risk for malnutrition. Malnutrition and weight loss,
      in turn, are associated with poorer prognosis, treatment tolerance and response,
      performance status, QoL and survival. Consequently, a multiple symptom
      intervention approach focusing on N&V as core symptoms is recommended. Clinicians
      should genuinely consider combining essential antiemetic therapies with other
      evidence-based pharmacological (e.g. nausea: psychotropics, such as olanzapine)
      and non-pharmacological approaches (e.g. N&V: relaxation) in attempts to not only
      improve prevention and control of N&V for their patients, but also reduce the
      synergistic impact of cluster symptoms (e.g. N&V, appetite loss) as a whole and
      resultant QoL impairment likewise. Where associated symptoms are not adequately
      controlled by these antiemetic-based interventions, targeted evidence-based
      strategies should be supplemented.

PMID- 22976924
TI  - Prostate epithelial AR inactivation leads to increased intraprostatic androgen
      synthesis.
AB  - BACKGROUND: Regulation of steroid synthesis within the prostate is not well
      understood. In this study, we examined androgen synthesis and metabolism in the
      mouse prostate. METHODS: Using LC-MSMS steroid assays, immunohistochemistry and
      real-time PCR we examined the role of prostate epithelial AR in regulating
      5alphaR expression and subsequent androgen metabolism by analyzing natural
      differences in epithelial AR expression between lobes as well as in the prostate
      epithelial AR knockout (PEARKO) mouse model. Subsequently, the role of
      intraprostatic androgen metabolism and epithelial AR in the generation and
      progression of prostate epithelial pathology was examined using long-term
      exogenous testosterone (T) + estradiol (E2) exposure. RESULTS: Epithelial AR and
      5alphaR2 expression as well as intraprostatic DHT followed the same lobe-specific
      pattern being lower in anterior than the other lobes (n = 6-8, P < 0.05). Lobe
      specific 5alphaR2 expression was similar in PEARKO and wild-type (WT) prostate.
      However, PEARKO prostate had higher intraprostatic DHT content with significantly
      increased 5alphaR2 expression localized in abnormal epithelium. T + E2 treatment
      induced epithelial pathology was more common in PEARKO prostate compared to WT
      (20% vs. 2%), and was associated with increased 5alphaR2 expression (n = 6, P <
      0.001). CONCLUSIONS: We suggest that androgen synthesis via 5alphaR2 expression
      is driven by its own product (DHT) acting on adjacent stromal cells in a
      paracrine loop leading to increased in situ androgen levels in the PEARKO
      prostate. This may form part of a feed-forward loop that promotes the development
      of epithelial pathology.

PMID- 22976925
TI  - Near IR fluorescent polystyrene/albumin core/shell nanoparticles for specific
      targeting of colonic neoplasms.
AB  - Previous studies have shown that albumin has a high affinity towards tumours,
      and, as a result, many drug/albumin conjugates, as well as albumin nanoparticles,
      have been studied as antineoplastic drug carriers. Numerous studies have also
      shown the high affinity of cyanine dyes for albumin. This work combines the
      former and the latter for the preparation of NIR fluorescent and photostable
      nanoparticles as diagnostic biomaterials. Tumour-specific labelling by NIR
      fluorescent polystyrene/albumin core/shell nanoparticles is demonstrated, without
      the presence of additional targeting moieties, and they possess great potential
      for clinical applications.

PMID- 22976927
TI  - Quantitative emergence of hetero[4]rotaxanes by template-directed click
      chemistry.
AB  - In one fell swoop, polyrotaxanes comprising up to 64 rings can be synthesized as
      a result of cucurbit[6]uril-templated 1,3-dipolar azide-alkyne cycloadditions
      accelerated in the presence of cyclodextrins as a consequence of self-sorting and
      positive cooperativity, brought about by hydrogen bonding. Mixing six components
      in one pot affords a hetero[4]rotaxane in one minute in quantitative yield.

PMID- 22976926
TI  - Dopamine transporter imaging is associated with long-term outcomes in Parkinson's
      disease.
AB  - Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for
      degenerative parkinsonism. Our aim was to measure the prognostic value of imaging
      for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively
      evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with
      a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and
      behavioral measures. DAT imaging with [(123)I][beta]-CIT and single-photon
      emission computerized tomography (SPECT) was performed at baseline and after 22
      months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on
      their baseline scan, consistent with PD, and were included in the analyses. The
      cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3
      (1.2). Lower striatal binding at baseline was independently associated with
      higher risk for clinical milestones and measures of disease severity, including
      motor-related disability, falling and postural instability, cognitive impairment,
      psychosis, and clinically important depressive symptoms. Subjects in the bottom
      quartile for striatal binding, compared to the top quartile, had an odds ratio
      (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9
      (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was
      also independently associated with motor, cognitive, and behavioral outcomes. DAT
      imaging with [(123)I][beta]-CIT and SPECT, shortly after the diagnosis of PD, was
      independently associated with clinically important long-term motor and nonmotor
      outcomes. These results should be treated as hypothesis generating and require
      confirmation.

PMID- 22976928
TI  - Plumbagin inhibits prostate cancer development in TRAMP mice via targeting
      PKCepsilon, Stat3 and neuroendocrine markers.
AB  - Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, is a quinoid constituent
      isolated from the roots of the medicinal plant Plumbago zeylanica L. (also known
      as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans
      cinerea (whitenut) and Juglans nigra (blacknut). The roots of P. zeylanica have
      been used in Indian and Chinese systems of medicine for more than 2500 years for
      the treatment of various types of ailments. We were the first to report that PL
      inhibits the growth and invasion of hormone refractory prostate cancer (PCa)
      cells [Aziz,M.H. et al. (2008) Plumbagin, a medicinal plant-derived
      naphthoquinone, is a novel inhibitor of the growth and invasion of hormone
      refractory prostate cancer. Cancer Res., 68, 9024-9032.]. Now, we present that PL
      inhibits in vivo PCa development in the transgenic adenocarcinoma of mouse
      prostate (TRAMP). PL treatment (2 mg/kg body weight i.p. in 0.2 ml phosphate
      buffered saline, 5 days a week) to FVB-TRAMP resulted in a significant (P < 0.01)
      decrease in prostate tumor size and urogenital apparatus weights at 13 and 20
      weeks. Histopathological analysis revealed that PL treatment inhibited
      progression of prostatic intraepithelial neoplasia (PIN) to poorly differentiated
      carcinoma (PDC). No animal exhibited diffuse tumor formation in PL-treated group
      at 13 weeks, whereas 75% of the vehicle-treated mice elicited diffuse PIN and
      large PDC at this stage. At 20 weeks, 25% of the PL-treated animals demonstrated
      diffuse PIN and 75% developed small PDC, whereas 100% of the vehicle-treated mice
      showed large PDC. PL treatment inhibited expression of protein kinase C epsilon
      (PKCepsilon), signal transducers and activators of transcription 3
      phosphorylation, proliferating cell nuclear antigen and neuroendocrine markers
      (synaptophysin and chromogranin-A) in excised prostate tumor tissues. Taken
      together, these results further suggest PL could be a novel chemopreventive agent
      against PCa.

PMID- 22976930
TI  - New perspectives on polyoxometalate catalysts: alcohol oxidation with Zn/Sb
      polyoxotungstates.

PMID- 22976929
TI  - Induction of aberrant trimethylation of histone H3 lysine 27 by inflammation in
      mouse colonic epithelial cells.
AB  - A field for cancerization (field defect), where genetic and epigenetic
      alterations are accumulated in normal-appearing tissues, is involved in human
      carcinogenesis, especially cancers associated with chronic inflammation. Although
      aberrant DNA methylation is involved in the field defect and induced by chronic
      inflammation, it is still unclear for trimethylation of histone H3 lysine 27
      (H3K27me3), which is involved in gene repression independent of DNA methylation
      and functions as a pre-mark for aberrant DNA methylation. In this study, using a
      mouse colitis model induced by dextran sulfate sodium (DSS), we aimed to clarify
      whether aberrant H3K27me3 is induced by inflammation and involved in a field
      defect. ChIP-on-chip analysis of colonic epithelial cells revealed that H3K27me3
      levels were increased or decreased for 266 genomic regions by aging, and more
      extensively (23 increased and 3574 decreased regions) by colitis. Such increase
      or decrease of H3K27me3 was induced as early as 2 weeks after the initiation of
      DSS treatment, and persisted at least for 16 weeks even after the inflammation
      disappeared. Some of the aberrant H3K27me3 in colonic epithelial cells was
      carried over into colon tumors. Furthermore, H3K27me3 acquired at Dapk1 by
      colitis was followed by increased DNA methylation, supporting its function as a
      pre-mark for aberrant DNA methylation. These results demonstrated that aberrant
      H3K27me3 can be induced by exposure to a specific environment, such as colitis,
      and suggested that aberrant histone modification, in addition to aberrant DNA
      methylation, is involved in the formation of a field defect.

PMID- 22976931
TI  - B lymphocytes in nonorgan-specific autoimmune diseases: implications for therapy.

PMID- 22976932
TI  - Incidence of hepatocellular carcinoma in HCV-infected patients with normal
      alanine aminotransferase levels categorized by Japanese treatment guidelines.
AB  - BACKGROUND: This study was conducted to evaluate Japanese treatment guidelines
      for patients with chronic hepatitis C virus (HCV) infection and normal alanine
      aminotransferase (N-ALT) levels from the viewpoint of the incidence of
      hepatocellular carcinoma (HCC). METHODS: Four groups of patients with chronic HCV
      infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and
      classified according to the N-ALT guidelines, were examined for HCC incidence:
      group A (n = 353), ALT <=30 IU/L and platelet (PLT) >=15 * 10(4)/mm(3); group B
      (n = 123), ALT <=30 IU/L and PLT <15 * 10(4)/mm(3); group C (n = 233), 30 < ALT
      <= 40 IU/L and PLT >=15 * 10(4)/mm(3); and group D (n = 100), 30 < ALT <= 40 IU/L
      and PLT <15 * 10(4)/mm(3). The mean observation period was 36.2 +/- 16.5 months
      RESULTS: In groups A and C, the HCC incidence was low even in patients with non
      response (NR) (cumulative rates at 3 years, 0.0 and 2.9 %, respectively). In
      groups B and D, 14.5 and 5.3 % of NR patients had developed HCC at 3 years, but
      none of the patients with sustained virologic response (SVR) or relapse had
      developed HCC. In group B, no patients with mild fibrosis developed HCC
      irrespective of the antiviral effect of the treatment. Among patients with PLT
      <15 * 10(4)/mm(3) (group B plus group D), the HCC incidence was significantly
      lower in patients with SVR and relapse than in NR patients (p < 0.001, p = 0.021,
      respectively). CONCLUSION: These results suggest that N-ALT patients with PLT <15
      * 10(4)/mm(3) could be candidates for early antiviral therapy.

PMID- 22976933
TI  - Association of enhanced activity of indoleamine 2,3-dioxygenase in dendritic
      cells with the induction of regulatory T cells in chronic hepatitis C infection.
AB  - BACKGROUND: Altered functions of dendritic cells (DCs) and/or increases of
      regulatory T cells (Tregs) are involved in the pathogenesis of chronic hepatitis
      C virus (HCV) infection. A tryptophan-catabolizing enzyme, indoleamine 2,3
      dioxygenase (IDO), is reported to be an inducer of immune tolerance. Our aim was
      to clarify whether or not IDO is activated in chronic hepatitis C patients and
      its role in immune responses. METHODS: This study enrolled 176 patients with
      chronic HCV infection and 37 healthy volunteers. Serum kynurenine concentration
      was evaluated by high-performance liquid chromatography, and its correlation with
      clinical parameters was examined. Monocyte-derived DCs were prepared from the
      subjects and subsequently stimulated with a combination of lipopolysaccharide and
      interferon-gamma to induce functional IDO (defined as IDO-DCs). The phenotypes,
      kynurenine or cytokine production, and T-cell responses with IDO-DCs were
      compared between the patients and healthy volunteers. RESULTS: The serum
      kynurenine level in the patients was significantly higher than that in the
      healthy volunteers, and the level of serum kynurenine was positively correlated
      with the histological activity or fibrosis score. IDO activity in IDO-DCs from
      the patients was significantly higher than that in IDO-DCs from the volunteers.
      Furthermore, IDO-DCs from the patients induced more Tregs in vitro compared with
      those from the volunteers, and the frequency of induced Tregs by IDO-DCs was
      decreased with an IDO-specific inhibitor. CONCLUSIONS: Systemic IDO activity is
      enhanced in chronic hepatitis C patients in correlation with the degree of liver
      inflammation and fibrosis. In response to inflammatory stimuli, DCs from the
      patients tend to induce Tregs, with some of this action being dependent on IDO.

PMID- 22976935
TI  - Evidences of the inflammasome pathway in chronic prostatitis and chronic pelvic
      pain syndrome in an animal model.
AB  - BACKGROUND: The mechanism of non-bacterial chronic prostatitis (CP/CPPS) has long
      been investigated but remains unclear. Under the hypothesis that abnormal
      response of innate immunity may be a cause of CP/CPPS, this study evaluated
      inflammasome, as part of innate immunity, and its effects on persist inflammation
      and CP/CPPS. METHODS: Carrageenan was used to induce CP/CPPS in a rat animal
      model. After confirming tactile hyper-algesia in the rats, their local prostate
      inflammation status, and inflammasome expression were determined. The amount of
      inflammasome and its downstream protein was checked, along with prostate
      localization. Chlorogenic acid (CHA), an active ingredient of Chinese herbal
      remedy for CP/CPPS treatment, was used as treatment. RESULTS: The rats had
      CP/CPPS once scrotal static tactile allodynia developed and CHA treatment
      relieved the scrotal hypersensitivity. Downstream inflammasome proteins like IL
      1beta and caspase 1 increased within the prostate and decreased with CHA
      treatment. Inflammasome, NALP1 but not NALP3, was significantly increased in the
      prostate glandular endothelial cells. Treatment with CHA also changed the
      distribution pattern of NALP1 in the prostate. CONCLUSIONS: There is a close
      relationship between activation of inflammasome and patho-physiologic changes of
      CP/CPSS in rats. Increased inflammasome may be a possible mechanism of CP/CPPS
      and clinically active regimen may inhibit the inflammasome-related pathway. This
      provides a new therapeutic rationale and approach for CP/CPPS treatment.

PMID- 22976934
TI  - Association between metabolic syndrome and prevalence of gastroesophageal reflux
      disease in a health screening facility in Japan.
AB  - BACKGROUND: Abdominal fat accumulation, which induces high intra-abdominal
      pressure that causes increase in the gastroesophageal pressure gradient and
      hiatal hernia, as well as obesity, has been shown to increase the prevalence of
      gastroesophageal reflux disease (GERD). This study was performed to clarify the
      association between metabolic syndrome and the prevalence of GERD. METHODS: The
      study subjects were an adult population who visited a medical center for annual
      medical check-ups from April 2010 to March 2011. GERD was diagnosed by the
      presence of endoscopically proven reflux esophagitis, GERD symptoms (QUEST score
      >=6), or current medical therapy for GERD. The presence of metabolic or pre
      metabolic syndrome was diagnosed based on the Japanese criteria for metabolic
      syndrome. RESULTS: Six hundred four (16.0 %) of 3775 study subjects were
      positively diagnosed with GERD, with the number of those with metabolic and pre
      metabolic syndrome being 477 (12.6 %) and 384 (10.2 %), respectively. Multiple
      logistic regression analysis showed that male gender, presence of hiatal hernia,
      and metabolic or pre-metabolic syndrome, as well as absence of gastric mucosal
      atrophy, were significant predictive factors for the prevalence of GERD, as were
      visceral fat accumulation and untreated dyslipidemia. Untreated hypertension and
      untreated hyperglycemia were also considered to be positive risk factors.
      Subjects undergoing treatment for hypertension showed an increased risk of GERD,
      while those undergoing treatment for dyslipidemia and diabetes mellitus showed a
      decreased risk. CONCLUSION: Metabolic syndrome is a reliable predictive factor
      for the prevalence of GERD, and medical therapy for metabolic syndrome may modify
      the risk of GERD occurrence.

PMID- 22976936
TI  - Surface roughness and charge influence the uptake of nanoparticles: fluorescently
      labeled pickering-type versus surfactant-stabilized nanoparticles.
AB  - The influence of surface roughness and charge on the cellular uptake of
      nanoparticles in HeLa cells is investigated with fluorescent, oppositely charged,
      rough, and smooth nanoparticles. Flow cytometry, cLSM, and TEM reveal that rough
      nanoparticles are internalized by the cells more slowly and by an unidentified
      uptake route as no predominant endocytosis route is blocked by a variety of
      inhibitory drugs, while the uptake of smooth nanoparticles is strongly dependent
      on dynamin, F-actin, and lipid-raft. Negatively charged nanoparticles are taken
      up to a higher extent than positively charged ones, independent of the surface
      roughness.

PMID- 22976938
TI  - Regio- and enantioselective cobalt-catalyzed reductive [3+2] cycloaddition
      reaction of alkynes with cyclic enones: a route to bicyclic tertiary alcohols.
AB  - Round and round: An unusual cobalt-catalyzed regio- and enantioselective
      reductive [3+2] cycloaddition of cyclic enones with alkynes affording bicyclic
      tertiary alcohols is described. A possible mechanism involving the formation of a
      cobaltacyclopentene intermediate is proposed.

PMID- 22976937
TI  - Cytomegalovirus retinitis as an adverse immunological effect of pulses of
      vincristine and dexamethasone in maintenance therapy for childhood acute
      lymphoblastic leukemia.
AB  - We describe a 5-year-old female with acute lymphoblastic leukemia (ALL) who
      suffered from cytomegalovirus (CMV) retinitis during maintenance therapy
      consisting of 6-mercaptopurine (6-MP) and methotrexate (MTX) with pulses of
      vincristine (VCR) and dexamethasone (DEX). Administration of anticytomegaloviral
      drugs led to a complete regression of active retinitis. Her low CD4 positive T
      cells and serum immunoglobulin G (IgG) recovered when maintenance therapy was
      resumed without VCR and DEX. The patient has been in complete remission (CR) for
      more than 5 months after completion of maintenance therapy without recurrence of
      CMV retinitis.

PMID- 22976939
TI  - A family with discordance between malignant hyperthermia susceptibility and
      rippling muscle disease.
AB  - Rippling muscle disease (RMD) is a disorder that affects striated muscle and
      involves disturbances in calcium homeostasis. Malignant hyperthermia
      susceptibility (MHS) is a potentially lethal disorder, characterized by extreme
      hypermetabolism and muscle rigidity/rhabdomyolysis during anesthesia with potent
      inhalational agents, in otherwise healthy individuals. The aim of this report was
      to search for a correlation between RMD and MHS in members of a family in which
      both disorders were present. Ten members of a large Swedish family segregating
      RMD were tested for MHS prior to establishing an RMD diagnosis. Results from
      diagnostic RMD investigations and anesthesia outcomes were collected and cross
      referenced to evaluate whether phenotype variations could be predicted by in
      vitro contracture test (IVCT) results suggestive of MHS. No correlation was found
      between individual RMD phenotypes and the IVCT results. There were no recorded
      adverse reactions to anesthesia, and RMD and MHS did not co-segregate. We
      conclude that RMD patients should not, on the basis of our present knowledge, be
      classified as having MHS; however, an increased surveillance for MH reactions is
      recommended in these patients.

PMID- 22976940
TI  - Central representation of spatial and temporal surface wave parameters in the
      African clawed frog.
AB  - Xenopus laevis employs mechano-sensory lateral lines to, for instance, capture
      arthropods on the surface of turbid waters with poor visibility based on incoming
      wave signals. To characterise central representations of surface waves emitted
      from different locations, responses to several wave parameters were
      extracellularly recorded across brainstem, midbrain and thalamic areas. Overall,
      339 of 411 statistically analysed responses showed significantly altered spike
      rates during the presentation of surface waves. Of these units, 45.1% were
      obtained in the torus semicircularis including its laminar subnucleus (23.3%)
      that is known to process auditory cues. Wave parameters contributing to central
      object representations were indicated by response rates that systematically
      varied with amplitude (76.3% of 160 tested units), frequency (74.4% of 270 tested
      units), source angle (93.7% of 79 tested units), or source distance (63.8% of 218
      tested units). Map-like parameter representations were rather diffuse, yet an
      increased fraction of units tuned to frontal source angles was observed at deeper
      tissue layers (>180 MUm), and an increased fraction of best neuronal responses to
      low wave frequencies (<=25 Hz) at rostral midbrain sections. Responses to wave
      frequencies remained largely robust across tested unit samples independent of
      source angles, and distances (N = 62). In comparison, spatial response
      characteristics seemed fragile across different wave frequencies in 68.3% of 41
      recordings.

PMID- 22976941
TI  - Laboratory studies of the impact of calcite on in vitro and in vivo effects of
      coal dust: a potential preventive agent for coal workers' pneumoconiosis?
AB  - BACKGROUND: Bioavailable iron (BAI) in coal, which may play a key role in causing
      coal workers' pneumoconiosis (CWP), is present at relatively high levels in
      Appalachian coals. Calcite decreases BAI and is more plentiful in Western coals
      than in Appalachian coals, possibly explaining the lower CWP prevalence among
      Western miners. METHODS: We measured effects of calcite on BAI in non-cellular
      and cellular systems involving Pennsylvania (PA) coal dust. We also tested in
      vivo effects of calcite on transferrin receptor and markers of epithelial
      mesenchymal transition (EMT) and inflammation in mice exposed to PA coal.
      RESULTS: Calcite rapidly eliminated BAI in an aqueous suspension of PA coal.
      Ferritin induction in human lung epithelial cells exposed to PA coal was
      effectively eliminated by calcite. Mouse lung tissue markers indicated increased
      EMT after exposure to PA coal dust, but not after exposure to PA coal plus
      calcite. Markers of inflammation increased following exposure to PA coal alone,
      but not following exposure to PA coal plus calcite. CONCLUSION: Additional
      research may lead to the use of supplemental calcite in coal mining as a safe and
      effective way to prevent CWP among Appalachian coal miners.

PMID- 22976942
TI  - Long non-coding RNAs coordinate cellular responses to stress.
AB  - Following the initial discovery of the heat shock RNA omega (hsromega) gene of
      Drosophila melanogaster to be non-coding (nc) and also inducible by cell stress,
      other stress-inducible long non-coding RNAs (lncRNA) have been described in
      diverse organisms. In view of the rapid sequence divergence of lncRNAs, present
      knowledge of stress trasncriptome is limited and fragmented. Several known stress
      related lncRNAs, associated with specific nuclear speckled domains or nucleolus,
      provide structural base for sequestering diverse RNA-processing/regulatory
      proteins. Others have roles in transcriptional or translational inhibition during
      stress or in signaling pathways; functions of several other lncRNAs are not yet
      known. Most stress-related lncRNAs act primarily by modulating activity of the
      proteins to which they bind or by sequestering specific sets of proteins away
      from the active pool. A common emerging theme is that a given lncRNA targets one
      or more protein/s with key role/s in the cascade of events triggered by the
      stress and therefore has a widespread integrative effect. Since proteins
      associate with RNA through short sequence motifs, the overall base sequence of
      functionally similar ncRNAs is often not conserved except for specific motifs.
      The rapid evolvability of ncRNA sequences provides elegant modules for
      adaptability to changing environment as binding of one or the other protein to
      ncRNA can alter its structure and functions in distinct ways. Thus the stress
      related lncRNAs act as hubs in the cellular networks to coordinate activities of
      the members within and between different networks to maintain cellular
      homeostasis for survival or to trigger cell death.

PMID- 22976943
TI  - Electrophilic trifluoromethanesulfanylation of organometallic species with
      trifluoromethanesulfanamides.

PMID- 22976944
TI  - Accumulated state assessment of the Yukon River watershed: part II quantitative
      effects-based analysis integrating Western science and traditional ecological
      knowledge.
AB  - This article is the second in a 2-part series assessing the accumulated state of
      the transboundary Yukon River (YR) basin in northern Canada and the United
      States. The determination of accumulated state based on available long-term (LT)
      discharge and water quality data is the first step in watershed cumulative effect
      assessment in the absence of sufficient biological monitoring data. Long-term
      trends in water quantity and quality were determined and a benchmark against
      which to measure change was defined for 5 major reaches along the YR for nitrate,
      total and dissolved organic carbon (TOC and DOC, respectively), total phosphate
      (TP), orthophosphate, pH, and specific conductivity. Deviations from the
      reference condition were identified as "hot moments" in time, nested within a
      reach. Significant increasing LT trends in discharge were found on the Canadian
      portion of the YR. There were significant LT decreases in nitrate, TOC, and TP at
      the Headwater reach, and significant increases in nitrate and specific
      conductivity at the Lower reach. Deviations from reference condition were found
      in all water quality variables but most notably during the ice-free period of the
      YR (May-Sept) and in the Lower reach. The greatest magnitudes of outliers were
      found during the spring freshet. This study also incorporated traditional
      ecological knowledge (TEK) into its assessment of accumulated state. In the
      summer of 2007 the YR Inter Tribal Watershed Council organized a team of people
      to paddle down the length of the YR as part of a "Healing Journey," where both
      Western Science and TEK paradigms were used. Water quality data were continuously
      collected and stories were shared between the team and communities along the YR.
      Healing Journey data were compared to the LT reference conditions and showed the
      summer of 2007 was abnormal compared to the LT water quality. This study showed
      the importance of establishing a reference condition by reach and season for key
      indicators of water health to measure change, and the importance of placing
      synoptic surveys into context of LT accumulated state assessments.

PMID- 22976945
TI  - A successful septal ablation of the first septal perforator artery arising from
      the circumflex artery.
AB  - Congenital coronary anomalies are usually incidental, uncommon and asymptomatic.
      We present a case of a successful septal ablation of the first septal perforator
      artery arising from the circumflex artery in a patient with symptomatic
      hypertrophic cardiomyopathy.

PMID- 22976946
TI  - The structure and folding of kink turns in RNA.
AB  - The kink turn (k-turn) is a widespread structural motif that introduces a tight
      kink into the axis of double-stranded RNA, with an included angle ~60 degrees . A
      standard k-turn comprises a three-nucleotide bulge followed on the 3' side by a
      G*A pair, an A*G pair, and usually further non-Watson-Crick pairs. The kinked
      conformation may be stabilized by three processes. These are the addition of
      metal ions, the binding of proteins such as the L7Ae family, and by the formation
      of tertiary interactions. The structure is characterized by specific A-minor
      interactions with the adenine nucleobases of the G*A pairs, and some very well
      conserved hydrogen bonds involving 2'-hydroxyl groups. We can identify two
      classes of k-turns, that differ in the manner of the hydrogen bonding at the
      adenine of the bulge-distal G*A pair.

PMID- 22976947
TI  - Threshold ionization of cobaltocene: the metallocene molecule revealing zero
      kinetic energy States.

PMID- 22976948
TI  - Fish community responses to multiple municipal wastewater inputs in a watershed.
AB  - Municipalities utilize aquatic environments to assimilate their domestic effluent
      resulting in eutrophication, anoxia, toxicity and endocrine disruption of aquatic
      biota. The objective of this study was to assess the potential cumulative impacts
      of municipal wastewater effluent (MWWE) discharges in the Grand River on the
      health status of a sentinel species and the fish community downstream of 2 MWWE
      discharges. The fish communities downstream of the MWWE outfalls demonstrated
      differences in the abundance and diversity, species and family richness, %
      tolerance and % vulnerability when compared to the fish community upstream or
      further downstream of these points of effluent discharge. In both years studied,
      the fish community exposed to MWWE in the riffle-run habitats demonstrated
      reductions in the proportion of the most prominent fish (Rainbow Darter,
      Ethoestoma caeruleum) downstream of the outfalls, and a significant increase in
      the proportion of large mobile, tolerant-omnivorous fish species such as suckers
      and sunfish. There was less variability in the responses of the fish community to
      MWWE in the same season between years than between seasons within the same year.
      An examination of how impaired health of a sentinel species exposed to MWWE
      discharges parallels changes in the fish community is also conducted. This study
      successfully demonstrates the cumulative impact of urban development, including
      multiple outfalls of treated wastewater effluents on fish populations and
      communities. Municipalities are the major source of nutrients and pharmaceuticals
      and personal care products to aquatic systems, and they need to consider their
      impacts carefully with increasing urban population growth and ageing
      demographics.

PMID- 22976949
TI  - (R)-alpha-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug as a
      multifunctional agent with potential neuroprotective activities.
AB  - The (R)-alpha-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug (LA-GPE, 1)
      was synthesized as a new multifunctional drug candidate with antioxidant and
      neuroprotective properties for the treatment of neurodegenerative diseases.
      Physicochemical properties, chemical and enzymatic stabilities were evaluated,
      along with the capacity of LA-GPE to penetrate the blood-brain barrier (BBB)
      according to an in vitro parallel artificial membrane permeability assay for the
      BBB. We also investigated the potential effectiveness of LA-GPE against the
      cytotoxicity induced by 6-hydroxydopamine (6-OHDA) and H2O2 on the human
      neuroblastoma cell line SH-SY5Y by using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1
      is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a
      pH-dependent permeability profile. Furthermore, LA-GPE was demonstrated to be
      significantly neuroprotective and to act as an antioxidant against H2O2- and 6
      OHDA-induced neurotoxicity in SH-SY5Y cells.

PMID- 22976950
TI  - An association and haplotype analysis of porcine maternal infanticide: a model
      for human puerperal psychosis?
AB  - An association analysis using the Illumina porcine SNP60 beadchip was performed
      to identify SNPs significantly associated with porcine maternal infanticide. We
      previously hypothesised that this was a good animal model for human puerperal
      psychosis, an extreme form of postnatal mood disorder. Animals were selected from
      carefully phenotyped unrelated infanticide and control groups (representing
      extremes of the phenotypic spectrum), from four different lines. Permutation and
      sliding window analyses and an analysis to see which haplotypes were in linkage
      disequilibrium (LD) were compared to identify concordant regions. Across all
      analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes
      associated with psychiatric or neurological disorders and were significant in
      multiple lines. The strongest (near GWS) consistent candidate region across all
      analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb,
      syntenic to a candidate region for bipolar disorder and another at 31.9 Mb,
      syntenic to a candidate region for human puerperal psychosis (16p13). From the
      haplotype/LD analysis, two regions reached genome wide significance (GWS): the
      first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one
      Duroc based breed and is syntenic to a region in humans associated with cognition
      and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two
      breeds and contained PAX3, which is expressed in the brain.

PMID- 22976951
TI  - Discovery of tyrosine kinase inhibitors by docking into an inactive kinase
      conformation generated by molecular dynamics.
AB  - Several small molecules that bind to the inactive DFG-out conformation of
      tyrosine kinases (called type II inhibitors) have shown a good selectivity
      profile over other kinase targets. To obtain a set of DFG-out structures, we
      performed an explicit solvent molecular dynamics (MD) simulation of the complex
      of the catalytic domain of a tyrosine kinase receptor, ephrin type-A receptor 3
      (EphA3), and a manually docked type II inhibitor. Automatic docking of four
      previously reported type II inhibitors was used to select a single snapshot from
      the MD trajectory for virtual screening. High-throughput docking of a
      pharmacophore-tailored library of 175,000 molecules resulted in about 4 million
      poses, which were further filtered by van der Waals efficiency and ranked
      according to a force-field-based energy function. Notably, around 20 % of the
      compounds with predicted binding energy smaller than -10 kcal mol(-1) are known
      type II inhibitors. Moreover, a series of 5-(piperazine-1-yl)isoquinoline
      derivatives was identified as a novel class of low-micromolar inhibitors of EphA3
      and unphosphorylated Abelson tyrosine kinase (Abl1). The in silico predicted
      binding mode of the new inhibitors suggested a similar affinity to the gatekeeper
      mutant T315I of Abl1, which was verified in vitro by using a competition binding
      assay. Additional evidence for the type II binding mode was obtained by two 300
      ns MD simulations of the complex between N-(3-chloro-4-(difluoromethoxy)phenyl)-2
      (4-(8-nitroisoquinolin-5-yl)piperazin-1-yl)acetamide and EphA3.

PMID- 22976952
TI  - Erythrocyte microparticles can induce kidney vaso-occlusions in a murine model of
      sickle cell disease.
AB  - Patients with sickle cell disease suffer from painful crises associated with
      disseminated vaso-occlusions, increased circulating erythrocyte microparticles
      (MPs), and thrombospondin-1 (TSP1). MPs are submicron membrane vesicles shed by
      compromised or activated cells. We hypothesized that TSP1 mediates MP shedding
      and participates in vaso-occlusions. We injected TSP1 to transgenic SAD mice with
      sickle cell disease and characterized circulating phosphatidylserine+ MPs by
      FACS. TSP1 stimulated MPs in plasma and initiated vaso-occlusions within minutes.
      In vitro, TSP1 triggered rapid erythrocyte conversion into spicule-covered
      echinocytes, followed by MP shedding. MP shedding was recapitulated by peptides
      derived from the TSP1 carboxyterminus. We purified MPs shed by erythrocytes in
      vitro and administered them back to SAD mice. MPs triggered immediate renal vaso
      occlusions. In vitro, MPs triggered the production of radical oxygen species by
      endothelial monolayers, favored erythrocyte adhesion, and induced endothelial
      apoptosis. MPs also compromised vasodilation in perfused microvessels. These
      effects were inhibited by saturating MP phosphatidylserine with annexin-V, or
      with inhibitors of endothelial ROS production. We conclude that TSP1 triggers
      erythrocyte MP shedding. These MPs induce endothelial injury and facilitate acute
      vaso-occlusive events in transgenic SAD mice. This work supports a novel concept
      that toxic erythrocyte MPs may connect sickle cell anemia to vascular disease.

PMID- 22976953
TI  - IL-21 in the bone marrow microenvironment contributes to IgM secretion and
      proliferation of malignant cells in Waldenstrom macroglobulinemia.
AB  - Cytokines within the tumor microenvironment play an important role in supporting
      the growth and survival of B-cell malignancies. One such cytokine, IL-21,
      promotes the growth of myeloma and Hodgkin lymphoma cells while inducing
      apoptosis in chronic lymphocytic leukemia. However, the biologic significance of
      IL-21 has not been examined in Waldenstrom macroglobulinemia (WM), a B-cell
      lymphoma characterized by elevated serum IgM and a lymphoplasmacytic bone marrow
      infiltrate. We report here on the presence of IL-21 in the bone marrow of
      patients with WM and have identified activated T cells as the source of this
      cytokine. We readily detected the IL-21 receptor on malignant WM B cells and show
      that IL-21 significantly increases both IgM secretion and cellular proliferation
      of these cells with no effect on viability. IL-21 rapidly induces phosphorylation
      of STAT3 in WM cells, and treatment of the WM cell line MWCL-1 with a STAT3
      inhibitor abolished the IL-21-mediated increases in cellular proliferation and
      IgM secretion. IL-21 also increased the expression of known STAT3 targets
      involved in B-cell differentiation, including BLIMP-1, XBP-1, IL-6, and IL-10.
      Overall, our data indicate that IL-21 in the bone marrow microenvironment
      significantly affects the biology of WM tumor cells through a STAT3-dependent
      mechanism.

PMID- 22976954
TI  - Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from
      ischemic stroke.
AB  - The devastating effect of ischemic stroke is attenuated in mice lacking
      conventional and unconventional T cells, suggesting that inflammation enhances
      tissue damage in cerebral ischemia. We explored the functional role of alphabeta
      and gammadelta T cells in a murine model of stroke and distinguished 2 different
      T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN
      gamma produced by CD4(+) T cells induced TNF-alpha production in macrophages,
      whereas IL-17A secreted by gammadelta T cells led to neutrophil recruitment. The
      synergistic effect of TNF-alpha and IL-17A on astrocytes resulted in enhanced
      secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A
      blocking antibody within 3 hours after stroke induction decreased infarct size
      and improved neurologic outcome in the murine model. In autoptic brain tissue of
      patients who had a stroke, we detected IL-17A-positive lymphocytes, suggesting
      that this aspect of the inflammatory cascade is also relevant in the human brain.
      We propose that selective targeting of IL-17A signaling might provide a new
      therapeutic option for the treatment of stroke.

PMID- 22976956
TI  - Commonly altered genomic regions in acute myeloid leukemia are enriched for
      somatic mutations involved in chromatin remodeling and splicing.
AB  - Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As
      commonly altered genomic regions point to candidate genes involved in
      leukemogenesis, we used microarray-based comparative genomic hybridization and
      single nucleotide polymorphism profiling data of 391 AML cases to further narrow
      down genomic regions of interest. Targeted resequencing of 1000 genes located in
      the critical regions was performed in a representative cohort of 50 AML samples
      comprising all major cytogenetic subgroups. We identified 120 missense/nonsense
      mutations as well as 60 insertions/deletions affecting 73 different genes (~ 3.6
      tumor-specific aberrations/AML). While most of the newly identified alterations
      were nonrecurrent, we observed an enrichment of mutations affecting genes
      involved in epigenetic regulation including known candidates like TET2, TET1,
      DNMT3A, and DNMT1, as well as mutations in the histone methyltransferases NSD1,
      EZH2, and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and
      in the nonclassic regulators of mRNA processing CTCF and RAD21. These splicing
      related mutations affected 10% of AML patients in a mutually exclusive manner. In
      conclusion, we could identify a large number of alterations in genes involved in
      aberrant splicing and epigenetic regulation in genomic regions commonly altered
      in AML, highlighting their important role in the molecular pathogenesis of AML.

PMID- 22976957
TI  - Editorial: bioinorganic chemistry (ICBIC XV).

PMID- 22976955
TI  - Inactivation of ribosomal protein L22 promotes transformation by induction of the
      stemness factor, Lin28B.
AB  - Ribosomal protein (RP) mutations in diseases such as 5q- syndrome both disrupt
      hematopoiesis and increase the risk of developing hematologic malignancy.
      However, the mechanism by which RP mutations increase cancer risk has remained an
      important unanswered question. We show here that monoallelic, germline
      inactivation of the ribosomal protein L22 (Rpl22) predisposes T-lineage
      progenitors to transformation. Indeed, RPL22 was found to be inactivated in ~ 10%
      of human T-acute lymphoblastic leukemias. Moreover, monoallelic loss of Rpl22
      accelerates development of thymic lymphoma in both a mouse model of T-cell
      malignancy and in acute transformation assays in vitro. We show that Rpl22
      inactivation enhances transformation potential through induction of the stemness
      factor, Lin28B. Our finding that Rpl22 inactivation promotes transformation by
      inducing expression of Lin28B provides the first insight into the mechanistic
      basis by which mutations in Rpl22, and perhaps some other RP genes, increases
      cancer risk.

PMID- 22976958
TI  - Kinetic and thermodynamic effects of mutations of human sulfite oxidase.

PMID- 22976959
TI  - Group-10 metal complexes of biological molecules and related ligands: structural
      and functional properties.
AB  - The complexes of group-10 metals, Ni, Pd, and Pt, with biological molecules and
      related ligands have been attracting increasing attention in recent years due to
      their reactivities and functions, such as catalysts and drugs, and their
      biological relevance. The well-defined structures and kinetic inertness
      especially of Pt complexes have been used as the sites for weak interactions with
      other molecules. The Ni complexes have been reported as models not only for Ni
      enzymes but also for other metalloenzyme active sites for deeper understanding of
      the reactivities such as oxygen activations and detailed electronic structures.
      Pd Complexes are widely known for their catalytic activities in conversions of
      various organic molecules including useful biological molecules, such as Suzuki
      Miyaura cross-coupling, while Pt complexes have been intensively studied for
      their antitumor activities. We focus in this review on our recent results on weak
      interactions and reactivities of the group-10 metal complexes with biological
      molecules and related compounds, and discuss their structural features and some
      new properties pointing to functional possibilities.

PMID- 22976960
TI  - Demetalation of chlorophyll pigments.
AB  - Natural chlorophylls (Chls) and bacteriochlorophyll (BChls), which are major
      pigments in photosynthesis, possess a central Mg (or Zn) in their cyclic
      tetrapyrrole macrocycles. Removal of the central metal atom from chlorophyllous
      pigments, called pheophytinization, is a biologically important reaction in that
      it allows production of the primary electron acceptors in photosystem II(-type)
      reaction centers and is one of the crucial steps in the Chl degradation pathway.
      Pheophytinization in processed and postharvest foods derived from vegetables and
      fruits has attracted considerable attention in agricultural and food chemistry
      from the viewpoints of maintenance of their color level and evaluation by
      consumers. In this review, we focus on in vivo demetalation reactions and
      demetalated products of chlorophyllous pigments. In addition, we summarize
      kinetic studies on in vitro demetalation of natural (B)Chl molecules and their
      synthetic analogs under acidic conditions.

PMID- 22976961
TI  - Fibrous supramolecular hemoprotein assemblies connected with synthetic heme dimer
      and apohemoprotein dimer.
AB  - Supramolecular hemoprotein assemblies via heme-heme pocket interaction were
      prepared by synthetic heme dimers containing a linker with charged amino acids
      and apohemoprotein disulfide dimers. The mixture of the negatively charged heme
      dimer and the apomyoglobin dimer provides heterotropic fibrous hemoprotein
      assemblies, which were characterized by size-exclusion chromatography (SEC) and
      atomic force microscopy (AFM).

PMID- 22976962
TI  - Electrochemical investigations of Tau protein phosphorylations and interactions
      with Pin1.
AB  - Phosphorylation of Tau by the protein kinase GSK-3beta was monitored by
      electrochemical impedance spectroscopy of immobilized Tau on gold surfaces. As a
      result of Tau phosphorylation, the film resistance decreases significantly due to
      conformational changes and reorganization of the immobilized phosphorylated Tau
      (pTau) protein, which in turn enables the interactions of pTau with the peptidyl
      prolyl cis/trans isomerase, Pin1. Interactions are specific to phospho-Ser (pSer)
      and phospho-Thr (pThr) residues of pTau. Impedance changes occurred as a function
      of pTau-Pin1 interactions and are related to the amount of Pin1 bound, which
      resulted in an increase of the charge-transfer resistance, R(CT). Our results
      clearly indicate that the isomerase Pin1 interacts favorably with pSer/pThr-Pro
      residues in Tau, but does not bind non-phosphorylated Tau or phospho-Tyr residues
      in Tau films. Our study demonstrates the utility of electrochemical impedance
      studies to probe protein modifications and biomolecular interactions.

PMID- 22976963
TI  - 3-Fluorotyrosine as a complementary probe of hemoglobin structure and dynamics: a
      (19)F-NMR study of Synechococcus sp. PCC 7002 GlbN.
AB  - The hemoglobin from the cyanobacterium Synechococcus sp. PCC 7002 (GlbN) contains
      three tyrosines (Tyr5, Tyr22, and Tyr53), each of which undergoes a structural
      rearrangement when the protein binds an exogenous ligand such as cyanide. We
      explored the use of 3-fluorotyrosine and (19)F-NMR spectroscopy for the
      characterization of GlbN. Assignment of (19)F resonances in fluorinated GlbN
      (GlbN*) was achieved with individual Tyr5Phe and Tyr53Phe replacements. We
      observed marked variations in chemical shift and linewidth reflecting the
      dependence of structural and dynamic properties on oxidation state, ligation
      state, and covalent attachment of the heme group. The isoelectronic complexes of
      ferric GlbN* with cyanide and ferrous GlbN* with carbon monoxide gave contrasting
      spectra, the latter exhibiting heterogeneity and enhanced internal motions on a
      microsecond-to-millisecond time scale. The strength of the H-bond network
      involving Tyr22 (B10) and bound cyanide was tested at high pH. 3-Fluorotyrosine
      at position 22 had a pK(a) value at least 3 units higher than its intrinsic
      value, 8.5. In addition, evidence was found for long-range communication among
      the tyrosine sites. These observations demonstrated the utility of the 3
      fluorotyrosine approach to gain insight in hemoglobin properties.

PMID- 22976964
TI  - Organometallic ruthenium and osmium compounds of pyridin-2- and -4-ones as
      potential anticancer agents.
AB  - Organometallic Ru(II) compounds are among the most widely studied anticancer
      agents. Functionalizing metal centers with biomolecule-derived ligands has been
      shown to be a promising strategy to improve the antiproliferative activity of
      metal-based chemotherapeutics. Herein, the synthesis of a series of novel 3
      hydroxypyridin-2-one-derived ligands and their M(II)(eta(6)-p-cymene) half
      sandwich complexes (M = Ru, Os) is described. The compounds were characterized by
      1D- and 2D-NMR spectroscopy, and elemental analysis.

PMID- 22976965
TI  - Density functional study on UV/VIS spectra of copper-protein active sites: the
      effect of mutations.
AB  - UV/VIS Electron excitation spectra have been computed for large, realistic model
      systems of the blue copper protein family. Fully quantum-chemical calculations at
      the density-functional theory level employing polarized triple-zeta basis sets
      have been performed on systems of over 120 atoms, without symmetry. Different
      mutants, with the ligating methionine of the wild type Cu center exchanged for
      histidine (M121H) and glutamine (M121Q), have been investigated in order to
      obtain insight about how the influence of the exact surrounding milieu of the Cu
      atom affects the computed spectrum. With sufficiently large model sizes,
      inclusion of the environment by using continuum solvation models do not change
      the spectra significantly. More direct and rigorous treatments are needed to
      reliably assess the effect of the surrounding protein on the electronic structure
      of the active sites.

PMID- 22976966
TI  - Native N-terminus nitrophorin 2 from the kissing bug: similarities to and
      differences from NP2(D1A).
AB  - The first amino acid of mature native nitrophorin 2 is aspartic acid, and when
      expressed in E. coli, the wild-type gene of the mature protein retains the
      methionine-0, which is produced by translation of the start codon. This form of
      NP2, (M0)NP2, has been found to have different properties from its D1A mutant,
      for which the Met0 is cleaved by the methionine aminopeptidase of E. coli (R. E.
      Berry, T. K. Shokhireva, I. Filippov, M. N. Shokhirev, H. Zhang, F. A. Walker,
      Biochemistry 2007, 46, 6830). Native N-terminus nitrophorin 2 ((DeltaM0)NP2) has
      been prepared by employing periplasmic expression of NP2 in E. coli using the
      pelB leader sequence from Erwinia carotovora, which is present in the pET-26b
      expression plasmid (Novagen). This paper details the similarities and differences
      between the three different N-terminal forms of nitrophorin 2, (M0)NP2, NP2(D1A),
      and (DeltaM0)NP2. It is found that the NMR spectra of high- and low-spin
      (DeltaM0)NP2 are essentially identical to those of NP2(D1A), but the rate and
      equilibrium constants for histamine and NO dissociation/association of the two
      are different.

PMID- 22976967
TI  - Correlating C-H bond cleavage with molybdenum reduction in xanthine oxidase.
AB  - We have performed a computational study of substrate C-H bond activation in
      enzymes of the XO family. The C-H H-atom for all XO substrates studied is
      transferred to the terminal sulfido at the transition state with near neutral
      charge, and this is consistent with both Mo=S pi-> C-H sigma* and C-H sigma->Mo=S
      pi* donor-acceptor interactions activating the C-H bond. A C-H bond scission and
      Mo reduction appear to be highly correlated along the reaction coordinate for all
      XO substrates studied, with Mo reduction being a continuous and exponential
      function of C-H bond breaking along the reaction coordinate.

PMID- 22976968
TI  - Insertion of an H-bonding residue into the distal pocket of the ferriheme protein
      nitrophorin 4: effect on nitrite-iron coordination and nitrite
      disproportionation.
AB  - Heme proteins are important entities for the metabolism of nitrite. Inspection of
      the structural features of the reported hemoprotein-nitrite crystal structures
      reveals that, except for nitrophorin 4 (NP4), H-bonding to the nitrite ligand is
      accomplished via histidine or arginine residues. These H-bonds probably play an
      important role for the nitrite coordination and/or reactivities. In nitrophorins,
      which catalyze the nitrite disproportionation reaction, such a residue is
      missing. Here, we report on the L130R mutant of the NP isoprotein NP4 that
      provides the Arg130 residue as part of the flexible G-H loop as a potential H
      bonding residue in the distal heme pocket. Similar to the wild-type protein,
      nitrite remains N-bonded in the crystal structure of NP4(L130R). However,
      spectroscopic investigations show that, in solution, a second ligand-rotational
      orientation exists, which is in fast-exchange equilibrium with the normal,
      parallel ligand orientation. Moreover, the nitrite disproportionation is
      inhibited in NP4(L130R). Comparison with another, also less active mutant
      NP4(D30N) suggests that the displacement of H(2)O molecules from the heme cavity
      prevents the proton donation pathway through Asp30.

PMID- 22976969
TI  - Molecular evolution, structure, and function of peroxidasins.
AB  - Peroxidasins represent the subfamily 2 of the peroxidase-cyclooxygenase
      superfamily and are closely related to chordata peroxidases (subfamily 1) and
      peroxinectins (subfamily 3). They are multidomain proteins containing a heme
      peroxidase domain with high homology to human lactoperoxidase that mediates one-
      and two-electron oxidation reactions. Additional domains of the secreted and
      glycosylated metalloproteins are type C-like immunoglobulin domains, typical
      leucine-rich repeats, as well as a von Willebrand factor C module. These are
      typical motifs of extracellular proteins that mediate protein-protein
      interactions. We have reconstructed the phylogeny of this new family of
      oxidoreductases and show the presence of four invertebrate clades as well as one
      vertebrate clade that includes also two different human representatives. The
      variability of domain assembly in the various clades was analyzed, as was the
      occurrence of relevant catalytic residues in the peroxidase domain based on the
      knowledge of catalysis of the mammalian homologues. Finally, the few reports on
      expression, localization, enzymatic activity, and physiological roles in the
      model organisms Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens
      are critically reviewed. Roles attributed to peroxidasins include antimicrobial
      defense, extracellular matrix formation, and consolidation at various
      developmental stages. Many research questions need to be solved in future,
      including detailed biochemical/physical studies and elucidation of the three
      dimensional structure of a model peroxidasin as well as the relation and
      interplay of the domains and the in vivo functions in various organisms including
      man.

PMID- 22976970
TI  - A synthetic pathway for an unsymmetrical N(5)O(2) heptadentate ligand and its
      heterodinuclear iron(III)zinc(II) complex: a biomimetic model for the purple acid
      phosphatases.
AB  - One major field of interest in bioinorganic chemistry is the design and synthesis
      of inorganic compounds with low molecular mass, showing structural,
      spectroscopic, and reactivity properties that mimic enzymes, such as purple acid
      phosphatases (PAPs). In this study, the unsymmetrical heptadentate ligand 2-[(4,7
      diisopropyl-1,4,7-triazacyclonon-1-yl)methyl]-6-{[(2-hydroxybenzyl)(pyridin-2
      ylmethyl)-amino]methyl}-4-methylphenol (H(2)L) and its first mixed-valence
      complex [Fe(III)Zn(II)(L)(MU-OAc)(2)]ClO(4)(1) were synthesized. Physical and
      chemical measurements (crystal structure, conductometry, IR and UV/VIS
      spectroscopy, and electrochemistry) were performed for 1, and these properties
      are compared with those presented by the kbPAPs active sites. Potentiometric
      titration studies of 1 have confirmed its acid/base properties that are crucial
      for the understanding of the phosphodiester and DNA catalytic cleavage in future
      studies.

PMID- 22976971
TI  - Binding of divalent metal ions to calcium-free peroxidase: thermodynamic and
      kinetic studies.
AB  - Thermodynamics of binding of divalent metal ions including Ca(2+), Mg(2+),
      Ba(2+), and Cd(2+) to Ca-free horseradish peroxidase (HRP) enzyme was
      investigated using UV/VIS spectrophotometry and molecular-mechanic (MM)
      calculations. According to the obtained binding and thermodynamic parameters,
      trend of the relative binding affinities of these divalent metal cations was
      found to be: Ca(2+) > Cd(2+) > Mg(2+) > Ba(2+). Binding analysis based on
      Scatchard and Hill models showed positive cooperativity effect between the two
      distal and proximal binding sites. Furthermore, kinetics of binding and
      reconstitution process was examined (using relaxation-time method) for binding of
      Ca(2+) (as the typical metal ion) to Ca-free HRP, which was found a second-order
      type having a two-step mechanism involving fast formation of Ca-free HRP/1 Ca(2+)
      as the kinetic intermediate in step 1. Finally, by means of MM calculations, the
      comparative stability energies were evaluated for binding of M(2+) metal cations
      to Ca-free HRP. Based on MM calculations, preferential binding of Ca(2+) ion was
      occurred on distal and proximal binding sites of Ca-free HRP associated with
      higher stability energies (E(total)). Indeed, among the divalent metal ions,
      Ca(2+) with the highest binding affinity (maximum value of K(bin) and minimum
      value of DeltaG(bin)(0)), maximum value of exothermic binding enthalpy, and
      stability energies stabilizes the HRP structure along with an optimized catalytic
      activity.

PMID- 22976972
TI  - Efficient room-temperature O-silylation of alcohols using a SBA-15-supported
      cobalt(II) nanocatalyst.
AB  - The O-silylation of OH groups of alcohols and phenols with hexamethyldisilazane
      (HMDS) was achieved in high-to-excellent yields using catalytic quantities of a
      SBA-15-supported cobalt(II) nanocatalyst (typically 0.5 mol-%) at room
      temperature and under solvent-free conditions. Furthermore, the heterogeneous
      catalyst showed an excellent durability and can be conveniently reused by
      filtration for at least twelve times without any noticeable loss of activity.

PMID- 22976973
TI  - Nitric oxide (NO)-induced death of gram-negative bacteria from a light-controlled
      NO-releasing platform.
AB  - A NO-delivery platform has been fabricated from polydimethylsiloxane (PDMS) and
      Pluronic((r)) F127 gel that contains the light-sensitive NO donor,
      [Mn(PaPy(3))(NO)]ClO(4). The material was assembled layer-by-layer. First, a thin
      PDMS membrane was cast. It was then layered with cold 25% (w/v) Pluronic((r))
      F127 gel mixed with [Mn(PaPy(3))(NO)]ClO(4). Finally, it was covered with a thick
      layer (nearly impermeable to NO) of PDMS (=polydimethoxysiloxane) to allow
      release of NO only from the thinner side upon exposure to light. Light-induced NO
      release from this layered material has been confirmed via NO-specific electrode
      and by a modified soft Griess-agar assay. Incorporation of ca. 8 mg/g of
      [Mn(PaPy(3))(NO)]ClO(4) in the Pluronic gel layer affords a material that
      drastically reduces the microbial loads of Acinetobacter baumannii and
      Pseudomonas aeruginosa via the antibiotic effects of the photoreleased NO.
      Application of this flexible layered NO-donating composite as bandage material
      has been proposed.

PMID- 22976974
TI  - Diamminetetrakis(carboxylato)platinum(IV) complexes--synthesis, characterization,
      and cytotoxicity.
AB  - A series of eight novel diamminetetrakis(carboxylato)platinum(IV) complexes was
      synthesized and characterized by multinuclear (1)H-, (13)C-, (15)N-, and (195)Pt
      NMR spectroscopy. Their antiproliferative potency was evaluated in three human
      cancer cell lines representing ovarian (CH1), lung (A549), and colon carcinoma
      (SW480). In cisplatin-sensitive CH1 cancer cells, cytotoxicity was found in the
      low micromolar range, whereas, in inherently cisplatin-resistant A549 and SW480
      cells, the activity was very low or negligible. Astonishingly, raise in
      lipophilicity of the complexes, as found in the case of cisplatin analogs, did
      not result in a significant enhancement of the cytotoxic effect.

PMID- 22976975
TI  - The [(Cp)M(CO)(3)] (M=Re, (99m)Tc) building block for imaging agents and
      bioinorganic probes: perspectives and limitations.
AB  - Starting from asymmetric Thiele's acid derivatives, two different imaging probes
      [(99m)Tc(CO)(3)(CpR)] (R=potential targeting vector) are generated simultaneously
      in one-pot and from one substrate. This extends the previously introduced
      labeling strategy of metal-mediated retro-Diels-Alder reaction with HCp-R dimers.
      We demonstrate that chemically active functionalities such as hydroxamic acids
      are not following this labeling strategy. Adopting the principle of replacing
      phenyl rings by [Re(CO)(3)(Cp)] entities, potent histone deacetylase (HDAC)
      inhibiting Re analogs of suberoylanlilide hydroxamic acid (SAHA; N-hydroxy-N'
      phenyloctanediamide) were synthesized and characterized. Cytotoxic evaluation on
      different tumor cell lines revealed low IC(50) values [MUM] for these compounds,
      comparable to their purely organic congeners.

PMID- 22976976
TI  - Mono(maleonitriledithiolene)molybdenum(IV) and bis(MU-sulfido)-bridged
      dimolybdenum(V) complexes with Mo=S moiety.
AB  - Mono(maleonitriledithiolene)sulfidomolybdenum(IV) complex, [MoS(S(4))(mnt)](2-)
      (2; mnt=maleonitriledithiolene) was synthesized by the substitution reaction of a
      tetrasulfido ligand of the known [MoS(S(4))(2)](2-) (1) upon reaction with one or
      even excess equivalent of Na(2)(mnt) in aqueous MeCN solution in air.
      Surprisingly, 2 undergoes dimerization on treatment with alkyl halide such as MeI
      and PhCH(2)Br to form bis(MU-sulfido)dimolybdenum(V) species, [{MoS(mnt)}(2)(MU
      S)(2)](2-) (3). These complexes have been characterized by IR, UV/VIS
      spectroscopy, cyclic voltammetry, elemental analysis, and by X-ray crystal
      structure analysis. Differences in the relative stability and electrochemical
      behavior of 1, 2, and 3 have been correlated with theoretical calculations at DFT
      level.

PMID- 22976977
TI  - Directing the biosynthesis of putrebactin or desferrioxamine B in Shewanella
      putrefaciens through the upstream inhibition of ornithine decarboxylase.
AB  - To manage iron acquisition in an oxic environment, Shewanella putrefaciens
      produces the macrocyclic dihydroxamic acid putrebactin (PB) as its native
      siderophore. In this work, we have established the siderophore profile of S.
      putrefaciens in cultures augmented with the native PB precursor putrescine and in
      putrescine-depleted cultures. Compared to base medium, PB increased by two-fold
      in cultures of S. putrefaciens with 10 mM NaCl and 20 mM exogenous putrescine. In
      cultures augmented with 1,4-diaminobutan-2-one (DAB), PB decreased with only 0.02
      fold PB detectable at 10 mM DAB. As an ornithine decarboxylase (ODC) inhibitor,
      DAB depleted levels of endogenous putrescine which attenuated downstream PB
      assembly. Under putrescine-depleted conditions, S. putrefaciens produced as its
      replacement siderophore the cadaverine-based desferrioxamine B (DFO-B), as
      characterised by ESI-MS of the Fe(III)-loaded form (m/z(obs) 614.13; m/z(calc)
      614.27). A third siderophore, independent of DAB, was observed in low levels.
      LC/MS Analysis of the Fe(III)-loaded extract gave m/z(obs) 440.93, which,
      formulated as a 1:1 Fe(III) complex with a macrocyclic dihydroxamic acid,
      comprising one putrescine- and one cadaverine-based precursor (m/z(calc) 440.14).
      These results show that the production of native PB or non-native DFO-B by S.
      putrefaciens can be directed though upstream inhibition of ODC. This approach
      could be used to increase the molecular diversity of siderophores produced by S.
      putrefaciens and to map alternative diamine-dependent metabolites.

PMID- 22976978
TI  - Structure of malaria pigment and related propanoate-linked metalloporphyrin
      dimers.
AB  - Malaria pigment, the heme detoxification product of malaria's invasion,
      digestion, and growth inside mammalian red blood cells, is an insoluble phase of
      iron(III)protoporphyrin-IX. Even though its structure was determined in 2000 by
      powder X-ray diffraction, significant questions remain about its formation and
      possible interaction with quinoline antimalarial drugs. A recent structural
      study, also with X-ray powder diffraction, has reconfirmed that the material
      isolated from the parasite is isostructural with its synthetic equivalent. It was
      recently suggested that other isomers may also be formed and may be present in
      synthetic samples. In particular, a series of stereoisomers are possible for the
      arrangement of vinyl groups on the periphery of the dimerized porphyrin rings. In
      principle, any given dimer can have vinyl groups at the alpha or beta sites, and
      at gamma or delta sites. In this paper, several models are evaluated, both
      biphasic and homogeneous methyl/vinyl disorder, against several sets of
      diffraction data, both published and new. We conclude that methyl/vinyl disorder
      is intrinsic to the system, and that the evidence at hand does not support the
      existence of any other crystalline isomers in carefully prepared samples of
      either natural or synthetic samples. Finally, the porphyrin-porphyrin
      interactions are evaluated using Scheidt's indicies for porphyrin pi-stacking,
      and we find modest to weak pi-interactions in these condensed phases.

PMID- 22976979
TI  - Syntheses, characterization, and antitumor activities of platinum(II) and
      palladium(II) complexes with sugar-conjugated triazole ligands.
AB  - Four platinum(II) and palladium(II) complexes with sugar-conjugated bipyridine
      type triazole ligands, [Pt(II)Cl(2)(AcGlc-pyta)] (3), [Pd(II)Cl(2)(AcGlc-pyta)]
      (4), [Pt(II)Cl(2)(Glc-pyta)] (5), and [Pd(II)Cl(2)(Glc-pyta)] (6), were prepared
      and characterized by mass spectrometry, elemental analysis, (1)H- and (13)C-NMR,
      IR as well as UV/VIS spectroscopy, where AcGlc-pyta and Glc-pyta denote 2-[4
      (pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl 2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranoside (1) and 2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl beta-D
      glucopyranoside (2), respectively. The solid-state structure of complex 6 was
      determined by single-crystal X-ray-diffraction analysis. These complexes
      exhibited in vitro cytotoxicity against human cervix tumor cells (HeLa) though
      weaker than that of cisplatin.

PMID- 22976980
TI  - Europium complexes as novel indicators of paracellular diffusion.
AB  - Measurement of paracellular permeation is an important assay for tight-junction
      investigations of drug toxicity, especially for metal-based drugs, and routine
      validation of the integrity of cell monolayers for models of drug absorption.
      Great efforts have been made in discovery and validation of novel paracellular
      diffusion indicators. In the present work, we prepared three Eu complexes, i.e.,
      [Eu(dtpa)] (dtpa=diethylenetriaminepentaacetic acid), [Eu(dtpa)(BSA)], and
      [Eu(dtpa)(PLL)] (PLL=poly(L-lysine)), and tested their permeation properties on
      Madin-Darby canine kidney (MDCK) cells. The experimental results showed that all
      three probes were nontoxic to MDCK cells, permeated across MDCK monolayer
      exclusively via the paracellular pathways, and responded well to the changes on
      tight junction with high correlation of P(app) values to the decrease of trans
      epithelial electric resistance (TEER). In addition, time-resolved fluorescence
      assays were conducted in a high-sensitivity and background-free mode. All these
      results confirmed the Eu complexes as novel and practical paracellular
      indicators.

PMID- 22976981
TI  - The need for combined inorganic, biochemical, and nutritional studies of
      chromium(III).
AB  - The history of biochemical and nutritional studies of the element is
      unfortunately full of twists and turns, most leading to dead ends. Chromium (Cr),
      as the trivalent ion, has been proposed to be an essential element, a body mass
      and muscle development agent, and, in the form of the most popular Cr-containing
      nutritional supplement, to be toxic when given orally to mammals. None of these
      proposals, despite significant attention in the popular media, has proven to be
      correct. Trivalent chromium has also been proposed as a therapeutic agent to
      increase insulin sensitivity and affect lipid metabolism, although a molecular
      mechanism for such actions has not been elucidated. Greater cooperative research
      interactions between nutritionists, biochemists, and chemists might have avoided
      the earlier issues in nutritional and biochemical Cr research and is necessary to
      establish the potential role of Cr as a therapeutic agent at a molecular level.

PMID- 22976982
TI  - Synthesis of glucopyranosyl Schiff base zinc(II) complexes capable of interacting
      with mononucleotides, and their DNA-cleavage activities.
AB  - New glucopyranosyl Schiff base zinc complexes, [Zn(GlcSal)(2) ] (1; GlcSalH=N-(2
      deoxy-beta-D-glucopyranos-2-yl-salicylaldimine) and [Zn(AcOGlcSal)(2) ] (2;
      AcOGlcSalH=N-(2-deoxy-beta-D-1,3,4,6-tetraacetylglucopyranos-2-yl
      salicylaldimine) were synthesized, and characterized by spectral and analytical
      methods. The interaction between the Zn complexes and mononucleotides was
      investigated by (1)H-NMR, (31)P-NMR and UV/VIS spectroscopies. Mononucleotides,
      cytidine 5'-monophosphate (CMP) and uridyl 5'-monophosphate (UMP), interacted
      with these complexes to form a 1:1 complex with 1 and a 1:2 complex with 2,
      depending on the presence of the OH group of glucopyranosyl substituents. The DNA
      cleavage activities of 1 and 2 were studied using plasmid DNA (pBR322) in a
      medium of 5 mM Tris.HCl/50 mM NaCl buffer in the presence of H(2)O(2). The DNA
      cleavage activity decreased in the order of 2>1>Zn(OAc)(2), indicating the
      significant promoting effect of the glucopyranosyl Schiff base ligand and the
      participation of the glucopyranosyl OH groups in the cleavage mechanism. The
      mechanism of the DNA cleavage by 1 and 2 was investigated by evaluation of the
      effect of a HO. radical scavenger and a singlet-oxygen ((1)O(2)) quencher under
      aerobic conditions. The former exhibited little effect, excluding the HO. radical
      as an active species and supporting the hydrolysis mechanism for the main process
      of the DNA cleavage. The latter quencher somewhat hindered the cleavage,
      indicating the partial participation of a (1)O(2) as a competitive active species
      in the present system.

PMID- 22976983
TI  - Coordination of thiosemicarbazones and bis(thiosemicarbazones) to bismuth(III) as
      a strategy for the design of metal-based antibacterial agents.
AB  - Complexes [Bi(2Fo4Ph)Cl(2)] (1), [Bi(2Ac4Ph)Cl(2)] (2), [Bi(2Bz4Ph)Cl(2)] (3),
      [Bi(H(2)Gy3DH)Cl(3)] (4), [Bi(H(2)Gy4Et)(OH)(2)Cl] (5), and [Bi(H(2)Gy4Ph)Cl(3)]
      (6) were prepared with pyridine-2-carbaldehyde 4-phenylthiosemicarbazone
      (H2Fo4Ph), 1-(pyridin-2-yl)ethanone 4-phenylthiosemicarbazone (H2Ac4Ph),
      phenyl(pyridin-2-yl)methanone 4-phenylthiosemicarbazone (H2Bz4Ph), as well as
      with glyoxaldehyde bis(thiosemicarbazone) (H(2)Gy4DH) and its 4-Et (H(2)Gy4Et)
      and 4-Ph (H(2)Gy4Ph) derivatives. The complexes exhibited antibacterial
      activities against Staphylococcus aureus, Staphylococcus epidermidis,
      Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to Bi(III) proved
      to be an effective strategy to increase the antibacterial activity of the
      thiosemicarbazones and bis(thiosemicarbazones).

PMID- 22976984
TI  - Microbial metalloproteomes explored using MIRAGE.
AB  - Metalloproteomics is a rapidly developing field of science that involves the
      comprehensive analysis of all metal-containing or metal-binding proteins in a
      biological sample. The purpose of this review is to offer an overview of the
      research involving Metal Isotope native RadioAutography in Gel Electrophoresis
      (MIRAGE), a powerful new method to visualize and study the proteome of a
      particular metal ion. MIRAGE involves four steps: i) labelling of target proteins
      with a radioisotope; ii) separation of intact holo-proteins using native
      isoelectric focusing (1D) combined with Blue Native PAGE (2D); iii) spot
      visualization and quantification using autoradiography; and iv) protein
      identification by tandem mass spectrometry. MIRAGE Investigations of the soluble
      Cu, Zn, and Fe metalloproteomes of Escherichia coli, and of the soluble Mo and W
      proteomes of the hyperthermophilic archaeon Pyrococcus furiosus are reviewed.

PMID- 22976985
TI  - A dynamic C-terminal segment in the Mycobacterium tuberculosis Mn/Fe R2lox
      protein can adopt a helical structure with possible functional consequences.
AB  - Mycobacterium tuberculosis R2-like ligand-binding oxidase (MtR2lox) belongs to a
      recently discovered group of proteins that are homologous to the ribonucleotide
      reductase R2 proteins. MtR2lox carries a heterodinuclear Mn/Fe cofactor and,
      unlike R2 proteins, a large ligand-binding cavity. A unique tyrosine-valine cross
      link is also found in the vicinity of the active site. To date, all known
      structures of R2 and R2lox proteins show a disordered C-terminal segment. Here,
      we present two new crystal forms of MtR2lox, revealing an ordered helical C
      terminal. The ability of alternating between an ordered and disordered state
      agrees well with bioinformatic analysis of the protein sequence. Interestingly,
      ordering of the C-terminal helix shields a large positively charged patch on the
      protein surface, potentially used for interaction with other cellular components.
      We hypothesize that the dynamic C-terminal segment may be involved in control of
      protein function in vivo.

PMID- 22976986
TI  - X-ray crystal structure of a mutant assimilatory nitrite reductase that shows
      sulfite reductase-like activity.
AB  - Assimilatory nitrite reductase (aNiR) reduces nitrite ions (NO(2)(-)) to ammonium
      ions (NH(4)(+)), whereas assimilatory sulfite reductase reduces sulfite (SO(3)(2
      )) to hydrogen sulfide (HS(-)). Although aNiR can also reduce SO(3)(2-), its
      activity is much lower than when NO(2)(-) is reduced as the substrate. To
      increase the SO(3)(2-)-reduction activity of aNiR, we performed a N226K mutation
      of Nii3, a representative aNiR. The resulting Nii3-N226K variant could bind non
      native targets, SO(3)(2-), and HCO(3)(-), in addition to its native target, i.e.,
      NO(2)(-). We have determined the high-resolution structure of Nii3-N226K in its
      apo-state and in complex with SO(3)(2-), NO(2)(-), and HCO(3)(-). This analysis
      revealed conformational changes of Lys226 and the adjacent Lys224 upon binding of
      SO(3)(2-), but not NO(2)(-)In contrast, HCO(3)(-) binding induced a
      conformational change at Arg179. After replacing Asn226 with a positively charged
      Lys, aNiR showed affinity for several anions. A comparison of all ligand-bound
      structures for Nii3-N226K revealed that structural changes in the active site
      depend on the size of the substrate.

PMID- 22976987
TI  - Ligand-incorporation site in 5-methylcytosine-detection probe modulating the site
      of osmium complexation with the target DNA.
AB  - ICON Probes, short DNA strands containing an adenine linked to a bipyridine
      ligand, formed an interstrand cross-link with 5-methylcytosine located opposite
      the modified adenine in the presence of an osmium oxidant. The location of a
      bipyridine-tethered adenine in the probes varied the selectivity of the reactive
      base. An ICON probe where the modified adenine was located at the probe center
      showed a 5-methylcytosine-selective osmium complexation, whereas an ICON probe
      with the modified adenine at the strand end exhibited high reactivity towards
      thymine as well as 5-methylcytosine. The modulation of reactive bases by the
      incorporation of a bipyridine-tethered adenine site made facilitates design of
      ICON probes for the fluorometric detection of 5-methylcytosine.

PMID- 22976988
TI  - Extent of intramolecular pi-stacks in aqueous solution in mixed-ligand copper(II)
      complexes formed by heteroaromatic amines and several 2-aminopurine derivatives
      of the antivirally active nucleotide analog 9-[2-(phosphonomethoxy)ethyl]adenine
      (PMEA).
AB  - The acidity constants of twofold protonated, antivirally active, acyclic
      nucleoside phosphonates (ANPs), H(2)(PE)(+/-), where PE(2-)=9-[2
      (phosphonomethoxy)ethyl]adenine (PMEA(2-)), 2-amino-9-[2
      (phosphonomethoxy)ethyl]purine (PME2AP(2-)), 2,6-diamino-9-[2
      (phosphonomethoxy)ethyl]purine (PMEDAP(2-)), or 2-amino-6-(dimethylamino)-9-[2
      (phosphonomethoxy)ethyl]purine (PME(2A6DMAP)(2-)), as well as the stability
      constants of the corresponding ternary Cu(Arm)(H;PE)(+) and Cu(Arm)(PE)
      complexes, where Arm=2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen), are
      compared. The constants for the systems containing PE(2-)=PMEDAP(2-) and
      PME(2A6DMAP)(2-) have been determined now by potentiometric pH titrations in
      aqueous solution at I=0.1M (NaNO(3)) and 25 degrees ; the corresponding results
      for the other ANPs were taken from our earlier work. The basicity of the terminal
      phosphonate group is very similar for all the ANP(2-) species, whereas the
      addition of a second amino substituent at the pyrimidine ring of the purine
      moiety significantly increases the basicity of the N(1) site. Detailed stability
      constant comparisons reveal that, in the monoprotonated ternary Cu(Arm)(H;PE)(+)
      complexes, the proton is at the phosphonate group, that the ether O-atom of the 
      CH(2)-O-CH(2)-P(O)(2)(-)(OH) residue participates, next to the P(O)(2)(-)(OH)
      group, to some extent in Cu(Arm)(2+) coordination, and that pi-pi stacking
      between the aromatic rings of Cu(Arm)(2+) and the purine moiety is rather
      important, especially for the H.PMEDAP(-) and H.PME(2A6DMAP)(-) ligands. There
      are indications that ternary Cu(Arm)(2+)-bridged stacks as well as unbridged
      (binary) stacks are formed. The ternary Cu(Arm)(PE) complexes are considerably
      more stable than the corresponding Cu(Arm)(R-PO(3)) species, where R-PO(3)(2-)
      represents a phosph(on)ate ligand with a group R that is unable to participate in
      any kind of intramolecular interaction within the complexes. The observed
      stability enhancements are mainly attributed to intramolecular-stack formation in
      the Cu(Arm)(PE) complexes and also, to a smaller extent, to the formation of five
      membered chelates involving the ether O-atom present in the -CH(2)-O-CH(2)
      PO(3)(2-) residue of the PE(2-) species. The quantitative analysis of the
      intramolecular equilibria involving three structurally different Cu(Arm)(PE)
      isomers shows that, e.g., ca. 1.5% of the Cu(phen)(PMEDAP) system exist with
      Cu(phen)(2+) solely coordinated to the phosphonate group, 4.5% as a five-membered
      chelate involving the ether O-atom of the -CH(2)-O-CH(2)-PO(3)(2-) residue, and
      94% with an intramolecular pi-pi stack between the purine moiety of PMEDAP(2-)
      and the aromatic rings of phen. Comparison of the various formation degrees of
      the species formed reveals that, in the Cu(phen)(PE) complexes, intramolecular
      stack formation is more pronounced than in the Cu(bpy)(PE) species. Within a
      given Cu(Arm)(2+) series the stacking intensity increases in the order PME2AP(2-)
      <PMEA(2-) <PMEDAP(2-) <PME(2A6DMAP)(2-). One could speculate that the reduced
      stacking intensity of PME2AP(2-), together with a different H-bonding pattern,
      could well lead to a different orientation of the 2-aminopurine moiety (compared
      to the adenine residue) in the active site of nucleic acid polymerases and thus
      be responsible for the reduced antiviral activity of PME2AP compared with that of
      PMEA and the other ANPs containing a 6-amino substituent.

PMID- 22976989
TI  - Unusually high-affinity Mg(2+) binding at the AU-rich sequence within the
      antiterminator hairpin of a Mg(2+) riboswitch.
AB  - Mg(2+)-Responsive riboswitches represent a fascinating example of bifunctional
      RNAs that sense Mg(2+) ions with high selectivity and autonomously regulate the
      expression of Mg(2+)-transporter proteins. The mechanism of the mgtA riboswitch
      is scarcely understood, and a detailed structural analysis is called for to study
      how this RNA can selectively recognize Mg(2+) and respond by switching between
      two alternative stem loop structures. In this work, we investigated the structure
      and Mg(2+)-binding properties of the lower part of the antiterminator loop C from
      the mgtA riboswitch of Yersinia enterocolitica by solution NMR and report a
      discrete Mg(2+)-binding site embedded in the AU-rich sequence. At the position of
      Mg(2+) binding, the helical axis exhibits a distinct kink accompanied by a
      widening of the major groove, which accommodates the Mg(2+)-binding pocket. An
      unusually large overlap between two adenine residues on the opposite strands
      suggests that the bending may be sequence-induced by strong stacking
      interactions, enabling Mg(2+) to bind at this so-far not described metal-ion
      binding site.

PMID- 22976990
TI  - Synthesis and acid-base properties of an imidazole-containing nucleotide analog,
      1-(2'-deoxy-beta-D-ribofuranosyl)imidazole 5'-monophosphate (dImMP(2-)).
AB  - Deletion of the substituted pyrimidine ring in purine-2'-deoxynucleoside 5'
      monophosphates leads to the artificial nucleotide analog dImMP(2-). This analog
      can be incorporated into DNA to yield, upon addition of Ag(+) ions, a molecular
      wire. Here, we measured the acidity constants of H(2)(dImMP)(+/-) having one
      proton at N(3) and one at the PO(3)(2-) group by potentiometric pH titrations in
      aqueous solution. The micro acidity constants show that N(3) is somewhat more
      basic than PO(3)(2-) and, consequently, the (H.dImMP)(-) tautomer with the proton
      at N(3) dominates to ca. 75%. The calculated micro acidity constants are
      confirmed by (31)P- and (1)H-NMR chemical shifts. The assembled data allow many
      quantitative comparisons, e.g., the N(3)-protonated and thus positively charged
      imidazole residue facilitates deprotonation of the P(O)(2)(OH)(-) group by 0.3 pK
      units. Information on the intrinsic site basicities also allows predictions about
      metal-ion binding; e.g., Mg(2+) and Mn(2+) will primarily coordinate to the
      phosphate group, whereas Ni(2+) and Cu(2+) will preferably bind to N(3).
      Macrochelate formation for these metal ions is also predicted. The micro acidity
      constant for N(3)H(+) deprotonation in the (H.dImMP.H)(+/-) species (pk(a) 6.46)
      and the M(n+)-binding properties are of relevance for understanding the behavior
      of dImMP units present in DNA hairpins and metalated duplexes.

PMID- 22976991
TI  - Quinoline-based, glucose-pendant fluorescent zinc probes.
AB  - Quinoline-based tetradentate ligands with glucose pendants, N,N'-bis[2-(beta-d
      glucopyranosyloxy)ethyl]-N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine
      (N,N'-6-MeOBQBGEN) and its N,N-counterpart, N,N-6-MeOBQBGEN, have been prepared,
      and their fluorescence-spectral changes upon Zn binding were investigated. Upon
      excitation at 336 nm, N,N'-6-MeOBQBGEN showed weak fluorescence (phi ~ 0.016) in
      HEPES buffer (HEPES 50 mM, KCl 100 mM, pH 7.5). In the presence of Zn, N,N'-6
      MeOBQBGEN exhibited a significant increase in fluorescence (phi = 0.096) at 414
      nm. The fluorescence enhancement is specific for Zn and Cd (I(Cd) /I(Zn) of 50%
      at 414 nm). On the other hand, N,N-6-MeOBQBGEN exhibited a smaller fluorescence
      enhancement upon Zn complexation (phi = 0.043, lambda(ex) = 334 nm, lambda(em) =
      407 nm) compared with N,N'-6-MeOBQBGEN. Fluorescence microscopic analysis using
      PC-12 rat adrenal cells revealed that N,N'-6-MeOBQBGEN exhibits a 1.8-fold higher
      fluorescence-signal response to Zn ion concentration compared with sugar-depleted
      compound 2 (N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine), due to its
      enhanced uptake into cells due to the targeting ability of the attached
      carbohydrates.

PMID- 22976992
TI  - Pyrolytic sugars from cellulosic biomass.
AB  - Depolymerization of cellulose offers the prospect of inexpensive sugars from
      biomass. Breaking the glycosidic bonds of cellulose to liberate glucose has
      usually been pursued by acid or enzymatic hydrolysis although a purely thermal
      depolymerization route to sugars is also possible. Fast pyrolysis of pure
      cellulose yields primarily the anhydrosugar levoglucosan (LG) whereas the
      presence of naturally occurring alkali and alkaline earth metals (AAEMs) in
      biomass strongly catalyzes ring-breaking reactions that favor formation of light
      oxygenates. Here, we show a method of significantly increasing the yield of
      sugars from biomass by purely thermal means through infusion of certain mineral
      acids (phosphoric and sulfuric acid) into the biomass to convert the AAEMs into
      thermally stable salts (particularly potassium sulfates and phosphates). These
      salts not only passivate AAEMs that normally catalyze fragmentation of pyranose
      rings, but also buffer the system at pH levels that favor glycosidic bond
      breakage. It appears that AAEM passivation contributes to 80 % of the enhancement
      in LG yield while the buffering effect of the acid salts contributes to the
      balance of the enhancement.

PMID- 22976993
TI  - Muscle patterning in mouse and human abdominal wall development and omphalocele
      specimens of humans.
AB  - Human omphalocele is a congenital defect of the abdominal wall in which the
      secondary abdominal wall structures (muscle and connective tissue) in an area
      centered around the umbilicus are replaced by a translucent membranous layer of
      tissue. Histological examination of omphalocele development and moreover the
      staging of normal human abdominal wall development has never been described. We
      hypothesized that omphalocele is the result of an arrest in the secondary
      abdominal wall development and predicted that we would observe delays in myoblast
      maturation and an arrest in secondary abdominal wall development. To look for
      evidence in support of our hypothesis, we performed a histological analysis of
      normal human abdominal wall development and compared this to mouse. We also
      conducted the first histological analysis of two human specimens with
      omphalocele. In these two omphalocele specimens, secondary abdominal wall
      development appears to have undergone an arrest around Carnegie Stage 19. In both
      specimens disruptions in the unidirectional orientation of myofibers were
      observed in the external and internal obliques, and rectus abdominis but not in
      the transversus abdominis. These latter findings support a model of normal
      abdominal wall development in which positional information instructs the
      orientation of myoblasts as they organize into individual muscle groups.

PMID- 22976994
TI  - Validation of questionnaire-based long-term dietary exposure to polychlorinated
      biphenyls using biomarkers.
AB  - SCOPE: The health consequences of lifelong low-level exposure to polychlorinated
      biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large
      population-based prospective studies addressing this issue. We validated long
      term food frequency questionnaire (FFQ)-based dietary PCB exposure against
      concentrations of six PCB congeners in serum. METHODS AND RESULTS: Dietary PCB
      exposure was estimated in the Swedish Mammography Cohort by constructing a recipe
      based database of CB-153, an indicator for total PCBs in food. The Spearman rank
      correlation (adjusted for within-person variability) was assessed between
      concurrent (2004-2006), past (1997), and long-term (mean of 1997 and 2004-2006)
      FFQ-based dietary PCB exposure, respectively, and the following serum PCB
      congeners, CB-118, CB-138, CB-153, CB-156, CB-170, and CB-180, in women (56-85
      years of age, n = 201). The correlation between FFQ-based dietary PCB exposure
      and serum CB-153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body
      weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure
      assessment. Long-term validity of FFQ-based PCB estimates and the six serum PCB
      congeners ranged from 0.30 to 0.58 (p < 0.05). CONCLUSION: FFQ-based PCB exposure
      estimates show acceptable validity in relation to PCB concentrations in serum,
      justifying their use in large-scale epidemiological studies.

PMID- 22976995
TI  - Induction chemoradiotherapy is superior to induction chemotherapy for the
      survival of non-small-cell lung cancer patients with pathological mediastinal
      lymph node metastasis.
AB  - OBJECTIVES: The purpose of this study was to compare the clinical outcomes of
      induction chemoradiotherapy and chemotherapy and to identify the prognostic
      factors for non-small-cell lung cancer patients with mediastinal lymph node
      metastasis who were treated with induction therapy. METHODS: Between August 1995
      and December 2010, 50 non-small-cell lung cancer patients with pathological
      mediastinal lymph node metastasis were scheduled to receive induction therapy
      followed by surgery. Irinotecan plus cisplatin was used for induction
      chemotherapy from June 1995 to April 1999, and docetaxel plus cisplatin with
      concurrent radiation at a dose of 40-46 Gy has been used for induction
      chemoradiotherapy since May 1999. RESULTS: Thirty-five patients were treated with
      induction chemoradiotherapy and 15 were treated with induction chemotherapy. For
      the entire population, the 3-year and 5-year overall survival rates were 64.1 and
      53.9%, respectively, and the 1-year and 2-year disease-free survival rates were
      70.0 and 53.1%, respectively. Among the clinicopathological factors, the
      chemoradiotherapy group exhibited longer overall survival and disease-free
      survival than the chemotherapy group (overall survival, P = 0.0020; disease-free
      survival, P = 0.015). Pathological downstaging was also significantly associated
      with favorable overall survival (P = 0.0042) and disease-free survival (P =
      0.021). A multivariate analysis showed that chemoradiotherapy (P = 0.0099) and
      pathological downstaging (P = 0.039) were independent prognostic factors.
      CONCLUSIONS: Our results indicated that induction chemoradiotherapy was superior
      to induction chemotherapy with regard to the outcome of non-small-cell lung
      cancer patients with mediastinal lymph node metastasis.

PMID- 22976996
TI  - Does the mode of exercise influence recovery of functional capacity in the early
      postoperative period after coronary artery bypass graft surgery? A randomized
      controlled trial.
AB  - OBJECTIVES: The purpose of this study was to compare the effectiveness of
      moderate-intensity stationary cycling and walking exercise programmes in the
      early postoperative period after first-time coronary artery bypass graft surgery.
      METHODS: In this prospective trial, 64 patients (57 men, 7 women, mean age = 66
      +/- 9 years) performed twice daily, moderate-intensity exercise sessions, of 10
      min duration, from postoperative day 3 until discharge from hospital. Patients
      were randomly assigned to stationary cycling or walking exercise intervention
      groups. Preoperative and discharge functional exercise capacity and health
      related quality of life were assessed using 6-min walk and cycle assessments and
      the SF-36 version 2.0 questionnaire. Compliance with exercise was calculated as
      the proportion of scheduled exercise sessions completed. RESULTS: There were no
      significant differences between intervention groups at hospital discharge for 6
      min walk distance (cyclists: 402 +/- 93 m vs walkers: 417 +/- 86 m, P = 0.803), 6
      min cycle work (cyclists: 15.0 +/- 6.4 kJ vs walkers: 14.0 +/- 6.3 kJ, P = 0.798)
      or health-related quality of life. There was no significant difference between
      intervention groups for postoperative length of hospital stay (P = 0.335).
      Compliance rates for intervention groups were cyclists: 185/246 (75%) scheduled
      exercise sessions completed vs walkers: 199/242 (82%) scheduled exercise sessions
      completed (P = 0.162). CONCLUSIONS: Stationary cycling provides a well-tolerated
      and clinically effective alternative to walking in the early postoperative period
      after coronary artery bypass graft surgery. The optimal frequency, intensity and
      duration of exercise in the early postoperative period require further
      investigation. (Clinical trials register: Australian New Zealand Clinical Trials
      Registry; identification number: ACTRN12608000359336;
      http://www.anzctr.org.au/trial_view.aspx?ID=82978).

PMID- 22976997
TI  - Is totally endoscopic coronary artery bypass safe, feasible and effective?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether totally endoscopic coronary artery bypass (TECAB)
      is safe, effective and feasible. A total of 171 papers were found, of which eight
      represented the best evidence. The authors, date, journal, study type,
      population, main outcome measures and results are tabulated. The da Vinci robotic
      system was utilized in seven retrospective studies and one multicentre
      prospective trial, comprising 724 patients undergoing TECAB. Patient-related
      outcomes, including the incidence of major adverse cardiac events, graft patency
      and survival, were investigated. From the studies evaluated, TECAB appears to be
      safe operation with low complication rates and excellent early- and mid-term
      graft patencies. The incidence of internal thoracic artery injury was documented
      in four studies and ranged from 0 to 10%. Re-exploration for bleeding was
      necessary in 1-15% of patients. Conversion to open techniques was performed in 0
      24% of cases. There was no in-hospital mortality in the majority of studies, but
      this reached 2.1% in a large series of 228 patients. Target-vessel reintervention
      rates varied between 0 and 12.1% according to the institutional experience. Pre-
      and post-discharge graft patencies were excellent at 93-100 and 92-100%,
      respectively. Intraoperative variables, such as time taken for internal thoracic
      artery harvest, anastomosis, cross-clamp, cardiopulmonary bypass (CPB) and the
      overall operation were as follows: internal thoracic artery harvest time (range 5
      187 min), anastomosis time (range 6-82 min), cross-clamp time (range 30-223 min),
      CPB time (range 41-268 min) and operative time (range 84-600 min). TECAB is a
      technically demanding and time-consuming procedure associated with a significant
      learning curve. Proctoring and structured training programmes are currently
      supported by European and international societies to encourage wider uptake of
      the procedure. In conclusion, TECAB represents a feasible alternative to
      conventional coronary artery bypass in selected patients. It is associated with
      low morbidity and excellent mid-term graft patency. Larger, prospective and
      multicentre trials are required to assess the long-term and patient-reported
      outcomes of TECAB.

PMID- 22976998
TI  - Wnt/beta-catenin signaling pathway upregulates c-Myc expression to promote cell
      proliferation of P19 teratocarcinoma cells.
AB  - Aberrant activation of the Wnt/beta-catenin signaling pathway is a common event
      in human tumor progression. Wnt signaling has also been implicated in maintaining
      a variety of adult and embryonic stem cells by imposing a restraint to
      differentiation. To understand the function and mechanism of Wnt/beta-catenin
      signaling on the pathogenesis of teratocarcinoma, we used the mouse
      teratocarcinoma P19 cell line as a model in vitro. Gsk3beta specific inhibitor
      (SB216763) was used to activate Wnt/beta-catenin signaling. All trans-retinoic
      acid (RA) was used to induce P19 cell differentiation. At different culture
      times, gene expression was examined by immunofluorescence staining, quantitative
      real-time PCR, and Western-blotting; BrdU incorporation assays were performed to
      measure P19 cell proliferation. Small interference RNA technology was used to
      downregulate c-myc expression. The results showed that SB216763 induced the
      nuclear translocation of beta-catenin, upregulated the expression of c-myc and
      pluripotency related genes, oct4, sox2 and nanog, and blocked cell
      differentiation induced by all trans-RA. The proliferation of P19 cells was
      significantly enhanced by SB216763, as well as c-myc overexpression. C-myc
      downregulation inhibited P19 cell proliferation caused by activation of Wnt/beta
      catenin signaling and induced P19 cell differentiation. In conclusion, activation
      of the Wnt/beta-catenin pathway could promote the proliferation and inhibit the
      differentiation of mouse teratocarcinoma cells by upregulation of c-myc
      expression.

PMID- 22976999
TI  - Comparing the distribution of strains with the distribution of bone tissue in a
      human mandible: a finite element study.
AB  - Comparative anatomy and experimental studies suggest that the mass and
      distribution of tissue within a bone is adapted to the strains the bone
      experiences during function. Finite element analysis is a powerful tool that can
      be used to investigate this since it allows the creation of hypothetical models
      with unadapted morphology. Here we use FE models of a human mandible with
      modified internal morphology to study the relationships between the gross
      distribution of bone tissue (i.e., the presence or absence of bone in a certain
      area), the variation of cortical bone thickness within the mandible and the
      distribution of strain magnitudes. We created one model in which all internal
      cavities were filled with cortical bone material and a second, hollow model with
      constant cortical bone thickness. In both the models, several load cases
      representing bites at different positions along the tooth row were applied and
      peak strain magnitudes across these load cases were calculated. The peak strain
      distributions in both models show striking similarities with the gross
      distribution of bone tissue and the variation of cortical thickness in the real
      mandible, but the correlation coefficients are rather low. These low coefficients
      could be explained by confounding factors and by the limited spectrum of load
      cases that were simulated. However, the correspondences we find between strain
      magnitude and bone tissue distribution suggest that models with altered internal
      geometry are useful in studying the mechanical adaptation of bone, especially in
      the absence of any in vivo strain data.

PMID- 22977000
TI  - Vascular injuries in the perioperative period.

PMID- 22977002
TI  - Direct analysis of cannabis samples by desorption atmospheric pressure
      photoionization-mass spectrometry.
AB  - Fast analysis of cannabis samples without prior sample preparation or
      chromatography was performed using desorption atmospheric pressure
      photoionization-mass spectrometry (DAPPI-MS). The MS(2) spectra of the molecular
      ions of tetrahydrocannabinol (THC) and cannabidiol (CBD) formed in DAPPI-MS
      showed distinct product ions, unlike the protonated molecules formed with other
      ambient mass spectrometry techniques, making possible the reliable identification
      of THC from cannabis samples.

PMID- 22977001
TI  - Harnessing the power of cell-penetrating peptides: activatable carriers for
      targeting systemic delivery of cancer therapeutics and imaging agents.
AB  - Targeted delivery of cancer therapeutics and imaging agents aims to enhance the
      accumulation of these molecules in a solid tumor while avoiding uptake in healthy
      tissues. Tumor-specific accumulation has been pursued with passive targeting by
      the enhanced permeability and retention effect, as well as with active targeting
      strategies. Active targeting is achieved by functionalization of carriers to
      allow specific interactions between the carrier and the tumor environment.
      Functionalization of carriers with ligands that specifically interact with
      overexpressed receptors on cancer cells represents a classic approach to active
      tumor targeting. Cell-penetrating peptides (CPPs) provide a non-specific and
      receptor-independent mechanism to enhance cellular uptake that offers an exciting
      alternative to traditional active targeting approaches. While the non-specificity
      of CPP-mediated internalization has the intriguing potential to make this
      approach applicable to a wide range of tumor types, their promiscuity is,
      however, a significant barrier to their clinical utility for systemically
      administered applications. Many approaches have been investigated to selectively
      turn on the function of systemically delivered CPP-functionalized carriers
      specifically in tumors to achieve targeted delivery of cancer therapeutics and
      imaging agents.

PMID- 22977003
TI  - Remember what I told you about therapeutic arteriogenesis, 11 years ago?

PMID- 22977005
TI  - Lack of ecto-5'-nucleotidase (CD73) promotes arteriogenesis.
AB  - AIMS: Adenosine can stimulate angiogenesis, but its role in the distinct process
      of arteriogenesis is unknown. We have previously reported that mice lacking ecto
      5'-nucleotidase (CD73-/-) show enhanced monocyte adhesion to the endothelium
      after ischaemia, which is considered to be an important trigger for
      arteriogenesis. METHODS AND RESULTS: Hindlimb ischaemia was induced in wild-type
      (WT) and CD73-/- mice to study the role of extracellularly formed adenosine in
      arteriogenesis. Magnetic resonance angiography (MRA) was performed for serial
      visualization of newly developed vessels at a spatial resolution of 1 nL, and
      high-energy phosphates (HEP) were quantified by (31)P MR spectroscopy (MRS). MRA
      of CD73-/- mice revealed substantially enhanced collateral artery conductance at
      day 7 [CD73-/-: 0.73 +/- 0.11 a.u. (arbitrary units); WT: 0.44 +/- 0.13 a.u.; P <
      0.01, n = 6], and MRS of the affected hindlimb showed a faster restoration of HEP
      in correlation with enhanced functional recovery in the mutant. Additionally,
      histology showed no differences in capillary density between the groups but
      showed an increased monocyte infiltration in hindlimbs of CD73-/- mice.
      CONCLUSION: Serial assessment of dynamic changes of vessel growth and metabolism
      in the process of arteriogenesis demonstrate that the lack of CD73-derived
      adenosine importantly promotes arteriogenesis but does not alter angiogenesis in
      our model of hindlimb ischaemia.

PMID- 22977007
TI  - Drug interaction networks: an introduction to translational and clinical
      applications.
AB  - This article introduces fundamental concepts to guide the analysis and
      interpretation of drug-target interaction networks. An overview of the generation
      and integration of interaction networks is followed by key strategies for
      extracting biologically meaningful information. The article highlights how this
      information can enable novel translational and clinically motivated applications.
      Important advances for the discovery of new treatments and for the detection of
      adverse drug effects are discussed. Examples of applications and findings
      originating from cardiovascular research are presented. The review ends with a
      discussion of crucial challenges and opportunities.

PMID- 22977006
TI  - Priming with synthetic oligonucleotides attenuates pressure overload-induced
      inflammation and cardiac hypertrophy in mice.
AB  - AIMS: Inflammation and Toll-like receptor (TLR) signalling have been linked to
      the development of cardiac hypertrophy following transverse aortic constriction
      (TAC). In the present study, we investigated whether pre-treatment with the
      synthetic TLR9 ligands 1668-thioate or 1612-thioate modulates the progression of
      TAC-induced cardiac inflammation and hypertrophy. METHODS AND RESULTS: C57BL/6N
      mice were pre-treated with 1668-thioate, 1612-thioate (0.25 nmol/g, i.p.), or
      phosphate-buffered saline 16 h prior to TAC or sham surgery. Heart-weight/body
      weight ratio (HW/BW), cardiomyocyte cell size, cellular macrophage accumulation,
      myofibroblast differentiation, and collagen deposition were investigated for up
      to 28 days. Cardiac function was monitored using a pressure-volume catheter and M
      mode echocardiography. Inflammatory gene expression in the heart was analysed via
      gene array, while the time course of mRNA expression of key inflammatory
      mediators was assessed via RT-qPCR. TAC increased the HW/BW ratio and
      cardiomyocyte cell size and induced macrophage accumulation, myofibroblast
      differentiation, and collagen deposition. These changes were accompanied by
      cardiac inflammation and a significant loss of left ventricular function. Pre
      treatment with cytosine-phosphate-guanine (CpG)-containing 1668-thioate
      attenuated the inflammatory response, the progression of cardiac hypertrophy, and
      cardiac remodelling, which resulted in a prolonged preservation of left
      ventricular function. These changes were induced to a smaller extent by the use
      of the non-CG-containing oligodeoxynucleotide 1612-thioate. CONCLUSION: Pre
      treatment with 1668-thioate attenuated cardiac hypertrophy following pressure
      overload, possibly by modifying the hypertrophy-induced inflammatory response,
      thereby reducing cardiac growth and fibrosis as well as delaying loss of cardiac
      function.

PMID- 22977008
TI  - Similar arrhythmicity in hypertrophic and fibrotic cardiac cultures caused by
      distinct substrate-specific mechanisms.
AB  - AIMS: Cardiac hypertrophy and fibrosis are associated with potentially lethal
      arrhythmias. As these substrates often occur simultaneously in one patient,
      distinguishing between pro-arrhythmic mechanisms is difficult. This hampers
      understanding of underlying pro-arrhythmic mechanisms and optimal treatment. This
      study investigates and compares arrhythmogeneity and underlying pro-arrhythmic
      mechanisms of either cardiac hypertrophy or fibrosis in in vitro models. METHODS
      AND RESULTS: Fibrosis was mimicked by free myofibroblast (MFB) proliferation in
      neonatal rat ventricular monolayers. Cultures with inhibited MFB proliferation
      were used as control or exposed to phenylephrine to induce hypertrophy. At Day 9,
      cultures were studied with patch-clamp and optical-mapping techniques and
      assessed for protein expression. In hypertrophic (n = 111) and fibrotic cultures
      (n = 107), conduction and repolarization were slowed. Triggered activity was
      commonly found in these substrates and led to high incidences of spontaneous re
      entrant arrhythmias [67.5% hypertrophic, 78.5% fibrotic vs. 2.9% in controls (n =
      102)] or focal arrhythmias (39.1, 51.7 vs. 8.8%, respectively). Kv4.3 and Cx43
      protein expression levels were decreased in hypertrophy but unaffected in
      fibrosis. Depolarization of cardiomyocytes (CMCs) was only found in fibrotic
      cultures (-48 +/- 7 vs. -66 +/- 7 mV in control, P < 0.001). L-type calcium
      channel blockade prevented arrhythmias in hypertrophy, but caused conduction
      block in fibrosis. Targeting heterocellular coupling by low doses of gap-junction
      uncouplers prevented arrhythmias by accelerating repolarization only in fibrotic
      cultures. CONCLUSION: Cultured hypertrophic or fibrotic myocardial tissues
      generated similar focal and re-entrant arrhythmias. These models revealed
      electrical remodelling of CMCs as a pro-arrhythmic mechanism of hypertrophy and
      MFB-induced depolarization of CMCs as a pro-arrhythmic mechanism of fibrosis.
      These findings provide novel mechanistic insight into substrate-specific
      arrhythmicity.

PMID- 22977009
TI  - Prolongation of minimal action potential duration in sustained fibrillation
      decreases complexity by transient destabilization.
AB  - AIMS: Sustained ventricular fibrillation (VF) is maintained by multiple stable
      rotors. Destabilization of sustained VF could be beneficial by affecting VF
      complexity (defined by the number of rotors). However, underlying mechanisms
      affecting VF stability are poorly understood. Therefore, the aim of this study
      was to correlate changes in arrhythmia complexity with changes in specific
      electrophysiological parameters, allowing a search for novel factors and
      underlying mechanisms affecting stability of sustained VF. METHODS AND RESULTS:
      Neonatal rat ventricular cardiomyocyte monolayers and Langendorff-perfused adult
      rat hearts were exposed to increasing dosages of the gap junctional uncoupler 2
      aminoethoxydiphenyl borate (2-APB) to induce arrhythmias. Ion channel
      blockers/openers were added to study effects on VF stability.
      Electrophysiological parameters were assessed by optical mapping and patch-clamp
      techniques. Arrhythmia complexity in cardiomyocyte cultures increased with
      increasing dosages of 2-APB (n > 38), leading to sustained VF: 0.0 +/- 0.1 phase
      singularities/cm(2) in controls vs. 0.0 +/- 0.1, 1.0 +/- 0.9, 3.3 +/- 3.2, 11.0
      +/- 10.1, and 54.3 +/- 21.7 in 5, 10, 15, 20, and 25 umol/L 2-APB, respectively.
      Arrhythmia complexity inversely correlated with wavelength. Lengthening of
      wavelength during fibrillation could only be induced by agents (BaCl(2)/BayK8644)
      increasing the action potential duration (APD) at maximal activation frequencies
      (minimal APD); 123 +/- 32%/117 +/- 24% of control. Minimal APD prolongation led
      to transient VF destabilization, shown by critical wavefront collision leading to
      rotor termination, followed by significant decreases in VF complexity and
      activation frequency (52%/37%). These key findings were reproduced ex vivo in rat
      hearts (n = 6 per group). CONCLUSION: These results show that stability of
      sustained fibrillation is regulated by minimal APD. Minimal APD prolongation
      leads to transient destabilization of fibrillation, ultimately decreasing VF
      complexity, thereby providing novel insights into anti-fibrillatory mechanisms.

PMID- 22977011
TI  - The inhibition of the potassium channel TASK-1 in rat cardiac muscle by
      endothelin-1 is mediated by phospholipase C.
AB  - AIMS: The two-pore-domain potassium channel TASK-1 is robustly inhibited by the
      activation of receptors coupled to the Galpha(q) subgroup of G-proteins, but the
      signal transduction pathway is still unclear. We have studied the mechanisms by
      which endothelin receptors inhibit the current carried by TASK-1 channels
      (I(TASK)) in cardiomyocytes. METHODS AND RESULTS: Patch-clamp measurements were
      carried out in isolated rat cardiomyocytes. I(TASK) was identified by
      extracellular acidification to pH 6.0 and by the application of the TASK-1
      blockers A293 and A1899. Endothelin-1 completely inhibited I(TASK) with an EC(50)
      of <10 nM; this effect was mainly mediated by endothelin-A receptors. Application
      of 20 nM endothelin-1 caused a significant increase in action potential duration
      under control conditions; this was significantly reduced after pre-incubation of
      the cardiomyocytes with 200 nM A1899. The inhibition of I(TASK) by endothelin-1
      was not affected by inhibitors of protein kinase C or rho kinase, but was
      strongly reduced by U73122, an inhibitor of phospholipase C (PLC). The ability of
      endothelin-1 to activate PLC-mediated signalling pathways was examined in
      mammalian cells transfected with TASK-1 and the endothelin-A receptor using patch
      clamp measurements and total internal reflection microscopy. U73122 prevented the
      inhibition of I(TASK) by endothelin-1 and blocked PLC-mediated signalling, as
      verified with a fluorescent probe for phosphatidylinositol-(4,5)-bisphosphate
      hydrolysis. CONCLUSION: Our results show that I(TASK) in rat cardiomyocytes is
      controlled by endothelin-1 and suggest that the inhibition of TASK-1 via
      endothelin receptors is mediated by the activation of PLC. The prolongation of
      the action potential observed with 20 nM endothelin-1 was mainly due to the
      inhibition of I(TASK).

PMID- 22977010
TI  - Early ischaemic preconditioning requires Akt- and PKA-mediated activation of eNOS
      via serine1176 phosphorylation.
AB  - AIMS: The role of endothelial nitric oxide synthase (eNOS)/NO signalling is well
      documented in late ischaemic preconditioning (IPC); however, the role of eNOS and
      its activation in early IPC remains controversial. This study investigates the
      role of eNOS in early IPC and the signalling pathways and molecular interactions
      that regulate eNOS activation during early IPC. METHODS AND RESULTS: Rat hearts
      were subjected to 30-min global ischaemia and reperfusion (I/R) with or without
      IPC (three cycles 5-min I and 5-min R) in the presence or absence of the NOS
      inhibitor l-NAME, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY),
      and protein kinase A (PKA) inhibitor H89 during IPC induction or prior
      endothelial permeablization. IPC improved post-ischaemic contractile function and
      reduced infarction compared with I/R with this being abrogated by l-NAME or
      endothelial permeablization. eNOS(Ser1176), Akt(Ser473), and PKA(Thr197)
      phosphorylation was increased following IPC. I/R decreased eNOS(Ser1176)
      phosphorylation, whereas IPC increased it. Mass spectroscopy confirmed
      eNOS(Ser1176) phosphorylation and quantitative Western blots showed ~24%
      modification of eNOS(Ser1176) following IPC. Immunoprecipitation demonstrated
      eNOS, Akt, and PKA complexation. Immunohistology showed IPC-induced Akt and PKA
      phosphorylation in cardiomyocytes and endothelium. With eNOS activation, IPC
      increased NO production as measured by electron paramagnetic resonance spin
      trapping and fluorescence microscopy. LY or H89 not only decreased Akt(Ser473) or
      PKA(Thr197) phosphorylation, respectively, but also abolished IPC-induced
      preservation of eNOS and eNOS(Ser1176) phosphorylation as well as
      cardioprotection. CONCLUSION: Thus, Akt- and PKA-mediated eNOS activation, with
      phosphorylation near the C-terminus, is critical for early IPC-induced
      cardioprotection, with eNOS-derived NO from the endothelium serving a critical
      role.

PMID- 22977012
TI  - Detection of PPARdelta agonists GW1516 and GW0742 and their metabolites in human
      urine.
AB  - Peroxisome proliferator-activated receptor-delta (PPARdelta) agonists are the
      drug candidates with potential performance-enhancing properties, and therefore
      their illegitimate use in sports should be controlled. To simulate the metabolism
      of PPARdelta agonist GW0742, in vitro reactions were performed which demonstrated
      that the main metabolic pathway is oxidation of the acyclic divalent sulfur to
      give the respective sulfoxide and sulfone. After being characterized by liquid
      chromatography-mass spectrometry (LC-MS), these metabolites were evaluated in
      urine samples collected after a controlled excretion study. For comparative
      purposes, GW1516 excretion study was also performed. It has been shown that
      GW1516 and GW0742 are best monitored as the sulfone metabolites which are
      detectable in urine using LC-MS/MS based procedure up to 40 and 20 days after a
      single oral dose of 15 mg each, respectively. The unmetabolized compounds are
      measurable only for a short period of time and at low ng/ml level. The sulfoxide
      to-sulfone ratio for both GW1516 and GW0742 changed irregularly in the range of
      1:3 to 1:15 depending on time elapsed after administration with a tendency of
      increasing the ratio with time. The other important finding was that the
      abundance of GW0742 and its metabolites in urine is about ten times lower than in
      case of GW1516.

PMID- 22977013
TI  - Persistent Mullerian duct syndrome: a rare cause of unilateral cryptorchidism.
AB  - Persistent Mullerian duct syndrome (PMDS) is a rare syndrome and sometimes the
      cause of a common problem in paediatric and surgical practice, namely undescended
      testes. PMDS is a recessive disease in which there is a defect in anti-Mullerian
      hormone secretion or receptor activity resulting in persistence of Mullerian
      structures such as a uterus or fallopian tubes with otherwise normal
      virilisation. Here the authors present a case of a 1&frac12;-year-old boy who was
      referred to their hospital because of unilateral cryptorchidism. During
      laparoscopic surgery, two gonads were present joined together by a uterus-like
      structure. Additional investigations showed a normal male karyotype and biopsies
      of the gonads revealed infantile testis parenchyma making the diagnosis PMDS
      likely.

PMID- 22977014
TI  - Determination of anti-convulsant and life-preserving capacities of three types of
      auto-injector therapies against soman intoxication in rats.
AB  - More effective countermeasures against nerve-agent poisoning are needed, because
      current ones do not protect sufficiently, particularly the central nervous system
      (CNS). The purpose of the present study was to make a comparison of the antidotal
      capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen),
      atropine/HI-6 (1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2
      [(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI-6 regimen), and
      scopolamine/HI-6/physostigmine (termed the physostigmine regimen) against various
      doses of soman (2, 3, 4 x LD50 ). The results showed that each regimen
      administered twice (1 min and 5 min after exposure) effectively prevented or
      terminated epileptiform activity within 10 min. However, the regimens differed
      markedly in life-saving properties with the physostigmine regimen ranking highest
      followed in descending order by the HI-6 and obidoxime regimens. Pretreatment
      with pyridostigmine increased the potency of the HI-6 regimen, but not the
      obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9
      min after exposure) did not compensate for the insufficiency. In half of the rats
      that lived for 7 days, neuropathology was unexpectedly observed predominantly in
      the left hemisphere unrelated to whether they seized or not. Local glutamatergic
      excitotoxic activity may occur even if manifest toxic signs are absent. The
      physostigmine regimen has excellent antidotal capacity, but the very narrow
      therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI-6
      regimen appears to constitute an efficacious therapy against lower doses of soman
      (2 and 3 x LD50).

PMID- 22977015
TI  - Indonesian undergraduate dental students' perceptions toward implant treatment
      and education.
AB  - OBJECTIVE: Indonesia foresees high demand in providing dental implant therapy and
      need to prepare competent graduating dentists. No information about undergraduate
      dental implant education in Indonesia has been reported in the literature. The
      objective of this study was to investigate dental students' perceptions towards
      implant treatment and education in one Indonesian dental school. METHODS: A
      survey was distributed to 166 fourth- and fifth-year students of Faculty of
      Dentistry, University of Indonesia (FD-UI). The survey consisted of 14 questions
      on students' perceptions on implant treatment, current undergraduate implant
      curriculum, and their future plans. RESULTS: One hundred and forty-one students
      (85%) returned the survey. Dental implant was considered as a treatment of choice
      for restoring missing mandibular first molar and maxillary anterior tooth, but
      not edentulous mandible. The majority of students rated that the topic of implant
      dentistry was insufficiently covered during undergraduate education, were
      interested in learning more, and planned to include implant as part of their
      future practice. CONCLUSION: Dental students of FD-UI are aware of implant
      treatment as a restorative option in replacing a single missing tooth. There is a
      need for a nationwide discussion for introducing a comprehensive implant
      dentistry curriculum in undergraduate dental education in Indonesia.

PMID- 22977016
TI  - Finite element analysis to compare stress distribution of gold alloy, lithium
      disilicate reinforced glass ceramic and zirconia based fixed partial denture.
AB  - AIM: Clinical data indicate that veneer chipping of zirconia core is more likely
      than with ceramic-fused-to-metal structures. The purposes of this simulation
      study were to: (a) use two-dimensional finite element modeling to simulate
      stresses at the interface of three-unit posterior fixed partial dentures (FPDs)
      made with three different core materials; and (b) to investigate the influence of
      three different veneer thicknesses on the stress distribution within the veneer
      core complex. METHODS: A mesio-distal cross-section of a three-unit FPD was
      digitized and used to create two-dimensional models of the teeth, supporting
      bone, different core materials (gold alloy, zirconia and lithia-disilicate
      reinforced glass ceramic), and different pontic preparation configurations
      (occlusal veneer thickness 1.0, 1.5, and 2.0 mm). A simulated 100 N vertical
      occlusal load was applied to the standardized pontic element. Compression stress
      and tensile stress values were calculated by finite element analysis along the
      veneer-core interface and compared. RESULTS: The veneer-core interfacial stress
      of zirconia-based FPD is greater than that of gold alloy and lithium-disilicate
      reinforced glass ceramic core. The veneer-core interface stress value decreased
      with increasing occlusal veneer thickness. CONCLUSIONS: Finite element modeling
      revealed differences in tensile and compressive stresses between different pontic
      preparation configurations and core materials. In general, gold alloy and lithium
      disilicate reinforced glass ceramic core provided more even stress distribution
      at the connector and pontic of fixed partial denture than a zirconia framework.

PMID- 22977017
TI  - Posttreatment CT and MR imaging in head and neck cancer: what the radiologist
      needs to know.
AB  - In patients with head and neck cancer, posttreatment imaging can be complicated
      and difficult to interpret because of the complexity of the surgical procedures
      performed and the postirradiation changes, but such imaging is critical for the
      evaluation of (a) the response to therapy and (b) tumor control. Posttreatment
      changes are affected by the type of surgery performed, reconstruction, neck
      dissection, and radiation therapy. Three types of flaps are used for
      reconstruction in the head and neck region: (a) the local flap, with geometric
      repositioning of adjacent tissue; (b) the pedicle flap, with rotation of donor
      tissue and preservation of the original vascular system; and (c) the free flap,
      with transfer of tissue that is revascularized by using microvascular surgical
      techniques. The posttreatment imaging findings in patients with head and neck
      cancer can be divided into four groups: altered anatomy secondary to surgical
      reconstruction, tumor recurrence, potential postsurgical complications, and
      possible postirradiation changes. Potential postsurgical complications are wound
      infection, abscess, fistula, flap necrosis, hematoma, chylous fistula, and serous
      retention. Possible postirradiation changes include mucosal necrosis,
      osteoradionecrosis, radiation-induced vasculopathy, radiation pneumonitis,
      radiation lung fibrosis, radiation-induced brain necrosis, and radiation-induced
      secondary malignancies. A familiarity with the imaging characteristics of
      posttreatment changes and of the potential complications caused by surgery and
      irradiation and an ability to differentiate these findings from tumor recurrence
      are essential for posttreatment surveillance and follow-up management of patients
      with head and neck cancer.

PMID- 22977018
TI  - Sequence-specific MR imaging findings that are useful in dating ischemic stroke.
AB  - Patients may present to the hospital at various times after an ischemic stroke.
      Many present weeks after a neurologic deficit has occurred, as is often the case
      with elderly patients and those in a nursing home. The ability to determine the
      age of an ischemic stroke provides useful clinical information for the patient,
      his or her family, and the medical team. Many times, perfusion imaging is not
      performed, and pulse sequence-specific magnetic resonance (MR) imaging findings
      may help determine the age of the infarct. The findings seen at apparent
      diffusion coefficient mapping and diffusion-weighted, fluid-attenuated inversion
      recovery (FLAIR) and unenhanced and contrast material-enhanced T1- and T2
      weighted gradient-echo and susceptibility-weighted MR imaging may help determine
      the relative age of a cerebral infarct. Strokes may be classified and dated as
      early hyperacute, late hyperacute, acute, subacute, or chronic. Recent data
      indicate that in many patients with restricted diffusion and no change on FLAIR
      images, it is more likely than was initially thought that the stroke is less than
      6 hours old. The time window to administer intravenous tissue plasminogen
      activator is currently 4.5 hours from the time when the patient was last seen to
      be normal, and for anterior circulation strokes, the time window for
      administering intraarterial tissue plasminogen activator is 6 hours from when the
      patient was last seen to be normal. For this reason, accurate dating is important
      in patients with ischemic stroke.

PMID- 22977019
TI  - AIRP best cases in radiologic-pathologic correlation: cerebral fat embolism
      syndrome in sickle cell beta-thalassemia.

PMID- 22977020
TI  - High-resolution MR imaging of the orbit in patients with retinoblastoma.
AB  - Retinoblastoma is the most common intraocular childhood malignancy, with a
      prevalence of one in 18,000 children younger than 5 years old in the United
      States. In 80% of patients, retinoblastoma is diagnosed before the age of three,
      and in 95% of patients, retinoblastoma is diagnosed before the age of five.
      Although reports exist of retinoblastoma in adults, onset beyond 6 years of age
      is rare. Broadly, retinoblastoma may be classified into two groups: sporadic and
      heritable. In either case, the origin of the tumor is a biallelic mutation in
      primitive neuroepithelial cells. Although their details vary, several staging
      schemes are used to describe the extent of retinoblastoma according to the
      following four general criteria: intraocular location, extraocular (extraorbital)
      location, central nervous system disease, and systemic metastases. In the past
      decade, substantial changes have taken place in terms of staging and monitoring
      treatment in patients with retinoblastoma. Diagnosis and treatment of
      retinoblastoma involve a multidisciplinary approach, for which imaging is a vital
      component. Increasing awareness and concerns about the effects of radiation in
      patients with retinoblastoma have led to a shift away from external-beam
      radiation therapy and toward chemotherapy and locoregional treatment, as well as
      the establishment of magnetic resonance imaging as the most important imaging
      modality for diagnosis, staging, and treatment monitoring.

PMID- 22977021
TI  - Deformable registration of preoperative PET/CT with postoperative radiation
      therapy planning CT in head and neck cancer.
AB  - In intensity-modulated radiation therapy (IMRT), precise target delineation is
      important to avoid underdosing areas at risk for recurrence and overdosing
      adjacent normal tissue. In postoperative radiation therapy of patients with head
      and neck cancer (HNC), surgical extirpation of tumor, anatomic changes resulting
      from tissue removal, and surgical reconstruction often obscure anatomic detail
      and may make it difficult to identify high-risk target volumes at postoperative
      planning computed tomography (CT). Positron emission tomography (PET)/CT can
      significantly affect CT-based tumor contours by providing information on both
      biologic and metabolic features of cancer. To incorporate diagnostic PET/CT into
      target delineation at postoperative CT, an advanced image registration method is
      required to overcome significant differences in patient position and anatomy
      between the imaging studies. Rigid registration can account for only linear or
      uniform transformation between the imaging datasets within six degrees of freedom
      (three rotations and three translations). However, deformable registration can
      account for significant temporal and anatomic changes between the corresponding
      images by computing nonlinear and nonuniform relationships between the volume
      elements across the imaging datasets. Use of deformable registration to integrate
      preoperative PET/CT with postoperative treatment planning CT is a powerful tool
      for target volume delineation in HNC patients undergoing postoperative IMRT.

PMID- 22977022
TI  - Radiation necrosis in the brain: imaging features and differentiation from tumor
      recurrence.
AB  - Radiation necrosis in the brain commonly occurs in three distinct clinical
      scenarios, namely, radiation therapy for head and neck malignancy or intracranial
      extraaxial tumor, stereotactic radiation therapy (including radiosurgery) for
      brain metastasis, and radiation therapy for primary brain tumors. Knowledge of
      the radiation treatment plan, amount of brain tissue included in the radiation
      port, type of radiation, location of the primary malignancy, and amount of time
      elapsed since radiation therapy is extremely important in determining whether the
      imaging abnormality represents radiation necrosis or recurrent tumor.
      Conventional magnetic resonance (MR) imaging findings of these two entities
      overlap considerably, and even at histopathologic analysis, tumor mixed with
      radiation necrosis is a common finding. Advanced imaging modalities such as
      diffusion tensor imaging and perfusion MR imaging (with calculation of certain
      specific parameters such as apparent diffusion coefficient ratios, relative peak
      height, and percentage of signal recovery), MR spectroscopy, and positron
      emission tomography can be useful in differentiating between recurrent tumor and
      radiation necrosis. In everyday practice, the visual assessment of diffusion
      weighted and perfusion images may also be helpful by favoring one diagnosis over
      the other, with restricted diffusion and an elevated relative cerebral blood
      volume being seen much more frequently in recurrent tumor than in radiation
      necrosis.

PMID- 22977024
TI  - Restoration of the radiologic-pathologic series: "From the radiologic pathology
      archives".

PMID- 22977025
TI  - From the radiologic pathology archives: cardiac lymphoma: radiologic-pathologic
      correlation.
AB  - Lymphoma of the heart and pericardium is usually present as one aspect of
      disseminated disease and rarely occurs as a primary malignancy. It accounts for
      1.3% of primary cardiac tumors and 0.5% of extranodal lymphomas. Cardiac
      lymphomas are most commonly diffuse large cell lymphomas and frequently manifest
      as an ill-defined, infiltrative mass. Atrial location is typical; the right
      atrium is most often affected. Pericardial thickening or effusion is often a
      common early feature of disease. Infiltration of atrial or ventricular walls with
      extension along epicardial surfaces is also a notable feature. At computed
      tomography, the attenuation of cardiac lymphoma may be similar to or lower than
      that of normal myocardium. At magnetic resonance imaging, it has variable signal
      intensity and contrast enhancement. Clinical manifestations may include
      pericardial effusion, cardiac arrhythmias, and a variety of nonspecific
      electrocardiographic abnormalities, notably first- to third-degree
      atrioventricular block. Treatment most commonly includes anthracycline-based
      chemotherapy and anti-CD20 treatment. Chemotherapy has been used alone or
      combined with radiation therapy. Palliative surgery has been performed, mainly
      for tumor debulking. The prognosis for patients with either primary or secondary
      lymphomatous heart involvement is usually poor; late diagnosis is one of the
      major factors affecting outcome.

PMID- 22977026
TI  - Myocardial tagging with MR imaging: overview of normal and pathologic findings.
AB  - Magnetic resonance tagging is used to evaluate the dynamic deformation of lines
      or grids superimposed on the myocardium during the cardiac cycle. From these
      data, a specific postprocessing procedure provides two kinds of metrics: (a)
      three orthogonal components of myocardial motion (longitudinal, circumferential,
      and radial), and (b) rotation and torsion. Strain expresses the local myocardial
      deformation and is prone to important physiologic heterogeneities. Peak systolic
      strain is in the range of -15% to -20% for the longitudinal and circumferential
      components (fiber shortening) and 30%-40% for the radial component (wall
      thickening). The helical arrangement of myofibers that run in opposite directions
      at the epicardium and endocardium explains systolic twist (~15 degrees ). This
      torsion may be enhanced during the early stage of several diseases (eg,
      hypertrophic cardiomyopathy) or in heart failure with a normal left ventricular
      ejection fraction. Strain is generally impaired in ischemic heart disease and
      cardiomyopathy, but the most diagnostically significant finding is the early
      identification of contractile dysfunction on the basis of longitudinal and
      circumferential strain reduction in patients with apparently preserved systolic
      function. Thus, strain impairment appears to be a sensitive and promising marker
      of subclinical disease, with the potential for improving patient management.

PMID- 22977027
TI  - CT and MR imaging of the aortic valve: radiologic-pathologic correlation.
AB  - Valvular disease is estimated to account for as many as 20% of cardiac surgical
      procedures performed in the United States. It may be congenital in origin or
      secondary to another disease process. One congenital anomaly, bicuspid aortic
      valve, is associated with increased incidence of stenosis, regurgitation,
      endocarditis, and aneurysmal dilatation of the aorta. A bicuspid valve has two
      cusps instead of the normal three; resultant fusion or poor excursion of the
      valve leaflets may lead to aortic stenosis, the presence of which is signaled by
      dephasing jets on magnetic resonance (MR) images. Surgery is generally
      recommended for patients with severe stenosis who are symptomatic or who have
      significant ventricular dysfunction; transcatheter aortic valve implantation
      (TAVI) is an emerging therapeutic option for patients who are not eligible for
      surgical treatment. Computed tomography (CT) is an essential component of
      preoperative planning for TAVI; it is used to determine the aortic root
      dimensions, severity of peripheral vascular disease, and status of the coronary
      arteries. Aortic regurgitation, which is caused by incompetent closure of the
      aortic valve, likewise leads to the appearance of jets on MR images. The severity
      of regurgitation is graded on the basis of valvular morphologic parameters;
      qualitative assessment of dephasing jets at Doppler ultrasonography; or
      measurements of the regurgitant fraction, volume, and orifice area. Mild
      regurgitation is managed conservatively, whereas severe or symptomatic
      regurgitation usually leads to valve replacement surgery, especially in the
      presence of substantial left ventricular enlargement or dysfunction. Bacterial
      endocarditis, although less common than aortic stenosis and regurgitation, is
      associated with substantial morbidity and mortality. Electrocardiographically
      gated CT reliably demonstrates infectious vegetations and benign excrescences of
      1 cm or more on the valve surface, allowing the assessment of any embolic
      complications.

PMID- 22977028
TI  - Effectiveness of MR enterography for the assessment of small-bowel diseases
      beyond Crohn disease.
AB  - The use of cross-sectional imaging techniques for the noninvasive evaluation of
      small-bowel disorders is increasing. The effectiveness of magnetic resonance (MR)
      enterography for the evaluation of Crohn disease, in particular, is well
      described in the literature. In addition, MR enterography has an evolving though
      less well documented role to play in the evaluation of other small-bowel
      diseases, including various benign and malignant neoplasms arising in isolation
      or in polyposis syndromes such as Peutz-Jeghers, inflammatory conditions such as
      vasculitis and treatment-induced enteritis, infectious processes, celiac disease,
      diverticular disease, systemic sclerosis, and bowel duplication. MR enterography
      may be useful also for the evaluation of intermittent and low-grade small-bowel
      obstructions. Advantages of MR imaging over computed tomography (CT) for
      enterographic evaluations include superb contrast resolution, lack of associated
      exposure to ionizing radiation, ability to acquire multiplanar primary image
      datasets, ability to acquire sequential image series over a long acquisition
      time, multiphasic imaging capability, and use of intravenous contrast media with
      better safety profiles. MR enterography also allows dynamic evaluations of small
      bowel peristalsis and distensibility of areas of luminal narrowing and
      intraluminal masses by repeating sequences at different intervals after
      administering an additional amount of the oral contrast medium. Limitations of MR
      enterography in comparison with CT include higher cost, less availability, more
      variable image quality, and lower spatial resolution. The advantages and
      disadvantages of MR enterography performed with ingestion of the oral contrast
      medium relative to MR enteroclysis performed with infusion of the oral contrast
      medium through a nasoenteric tube are less certain.

PMID- 22977029
TI  - MR imaging findings of ectopic pregnancy: a pictorial review.
AB  - Because of its lack of ionizing radiation and excellent soft-tissue contrast,
      magnetic resonance (MR) imaging is being increasingly used in the evaluation of
      acute abdominal pain in the pregnant patient. Roughly 2% of all pregnancies are
      ectopic. Although ectopic pregnancy is usually diagnosed on the basis of a
      combination of clinical, laboratory, and ultrasonographic findings, it
      occasionally is initially identified at MR imaging. Thus, it is imperative that
      the radiologist should be familiar with the variable appearance of ectopic
      pregnancy at MR imaging and should evaluate for ectopic pregnancy at any time
      when (a) a patient has positive results of a pregnancy test and (b) an
      intrauterine pregnancy is not definitively seen. Because of potential issues of
      fetal safety, a conservative approach should be used for MR imaging in pregnancy.
      An MR imaging protocol for the evaluation of possible appendicitis in pregnant
      women is detailed. Specific findings that can aid in the diagnosis of ectopic
      pregnancy are the lack of an intrauterine pregnancy, isolated hemoperitoneum,
      tubal masses, hematosalpinx, and interstitial masses. In the differential
      diagnosis of acute abdominal pain in pregnancy, consideration should be given to
      the more unusual forms of ectopic pregnancy, such as angular pregnancy, cornual
      pregnancy, and abdominal pregnancy. Potential mimics of ectopic pregnancy include
      placental abnormalities, ovarian neoplasms, and corpus luteum cysts.

PMID- 22977030
TI  - Utility of multidetector CT in severe postpartum hemorrhage.
AB  - Postpartum hemorrhage is one of the leading causes of maternal mortality
      worldwide. According to the time when postpartum hemorrhage develops, it is
      classified as (a) primary, or early, postpartum hemorrhage (within the first 24
      hours after delivery) or (b) secondary, or late, postpartum hemorrhage (>24 hours
      to 6 weeks after delivery). Primary postpartum hemorrhage may be caused by
      uterine atony (75%-90% of cases), trauma of the lower portion of the genital
      tract, uterine rupture, uterine inversion, bladder flap hematoma, retention of
      blood clots or placental fragments, and coagulation disorders. Secondary
      postpartum hemorrhage may be caused by uterine subinvolution, coagulopathies, and
      abnormalities of the uterine vasculature. Extrauterine sources of bleeding
      include rectus sheath hematoma, direct arterial injuries, and the HELLP
      (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Severe
      postpartum hemorrhage is a life-threatening condition that is diagnosed on the
      basis of the findings from clinical examination, with or without ultrasonography.
      Computed tomography (CT) and magnetic resonance imaging are useful in the
      characterization of postpartum hemorrhage when medical treatment fails.
      Multidetector CT has an important role when intraabdominal bleeding is suspected
      and can be considered in cases of recurrent bleeding after embolization, as well
      as for the evaluation of postsurgical complications. A proposed clinical and CT
      imaging algorithm for postpartum hemorrhage is presented. A multidisciplinary
      approach to postpartum hemorrhage is essential to optimize the role of diagnostic
      and interventional radiology in obstetric hemorrhage, to avoid hysterectomy and
      thus preserve fertility.

PMID- 22977031
TI  - Image-guided biopsy: what the interventional radiologist needs to know about
      PET/CT.
AB  - Positron emission tomography (PET)/computed tomography (CT) with fluorine 18
      fluorodeoxyglucose (FDG) is increasingly used in evaluation of oncology patients.
      Because PET/CT can demonstrate malignancy before morphologic changes are evident,
      application of PET/CT information to image-guided biopsy can facilitate early
      histologic diagnosis and staging. However, because FDG uptake is not specific to
      cancer, PET/CT findings may raise questions about whether uptake in a lesion is
      an indication for biopsy. To properly select patients for image-guided biopsy,
      interventional radiologists should be familiar with the biologic significance of
      FDG uptake and various causes of false-positive uptake. PET/CT images may also
      become a source of confusion in the interpretation of biopsy results. Various
      causes of false-positive and false-negative FDG uptake need to be considered,
      especially when there is a discrepancy between biopsy results and PET/CT
      findings. False-negative FDG uptake can result from cancers that are too small to
      be observed or not FDG avid. False-positive FDG uptake can be due to underlying
      inflammation from recent treatment. Conversely, complete resolution of FDG uptake
      in a treated lesion does not necessarily indicate absence of viable cells. When
      questions about PET/CT findings arise in the context of image-guided biopsy,
      discussion with experienced nuclear imaging physicians is essential.

PMID- 22977032
TI  - Multidetector CT features of mesenteric vein thrombosis.
AB  - Mesenteric vein thrombosis (MVT) accounts for 5%-15% of all mesenteric ischemic
      events and is classified as either primary or secondary. Primary MVT is
      idiopathic, whereas secondary MVT can result from a variety of underlying
      diseases and risk factors, including primary hypercoagulable states or
      prothrombotic disorders, myeloproliferative neoplasms, cancer (most frequently of
      the pancreas or liver), diverse inflammatory conditions, recent surgery, portal
      hypertension, and miscellaneous causes such as oral contraceptives or pregnancy.
      Clinical symptoms of MVT are rather nonspecific and are mainly characterized by
      abdominal pain. The mortality rate for MVT remains high, since even now the
      diagnosis is often delayed. Multidetector computed tomography (CT) is the
      modality of choice in this context. Although venous bowel ischemia occurs only
      infrequently with MVT, radiologists should be familiar with its multidetector CT
      features. Familiarity with the possible causes of MVT, the underlying pathogenic
      mechanisms associated with MVT, and the correlation between multidetector CT
      features and these pathogenic mechanisms is necessary to optimize medical
      management and improve patient care.

PMID- 22977033
TI  - AIRP best cases in radiologic-pathologic correlation: intraosseous lipoma.

PMID- 22977034
TI  - Scenes from the past: initial investigation of early jurassic vertebrate fossils
      with multidetector CT.
AB  - The study of fossils permits the reconstruction of past life on our planet and
      enhances our understanding of evolutionary processes. However, many fossils are
      difficult to recognize, being encased in a lithified matrix whose tedious removal
      is required before examination is possible. The authors describe the use of
      multidetector computed tomography (CT) in locating, identifying, and examining
      fossil remains of crocodilians (Mesosuchia) embedded in hard shale, all without
      removing the matrix. In addition, they describe how three-dimensional (3D)
      reformatted CT images provided details that were helpful for extraction and
      preparation. Multidetector CT can help experienced paleontologists localize and
      characterize fossils in the matrix of a promising rock specimen in a
      nondestructive manner. Moreover, with its capacity to generate highly accurate 3D
      images, multidetector CT can help determine whether the fossils warrant
      extraction and can assist in planning the extraction process. Thus, multidetector
      CT may well become an invaluable tool in the field of paleoradiology.

PMID- 22977035
TI  - Fat necrosis: BI-RADS 2 or 3?

PMID- 22977036
TI  - More on imaging assessment of the postoperative arthritic wrist.

PMID- 22977037
TI  - US of the eye made easy: a comprehensive how-to review with ophthalmoscopic
      correlation.
AB  - When performed by a trained examiner, ultrasonography (US) of the eye is a useful
      tool in diagnosing conditions of the ocular globe, especially when combined with
      ophthalmoscopy. Pathologic conditions of the ocular globe include several usual
      and unusual entities, most of which may be properly identified at US. For
      instance, the ocular globe may have an abnormal size or unusual morphologic
      characteristics. Lesions of the anterior chamber (eg, hyphema), lens (eg,
      cataract, luxation), and iris or ciliary bodies (eg, cysts) are usually seen at
      ophthalmoscopy but may also be depicted at US. Vitreous pathologic conditions may
      demonstrate echoes caused by various entities such as degeneration, asteroid
      hyalosis, hemorrhage, and infection, and lines are indicative of different types
      of detachment, including retinal, choroidal, and hyaloid detachment and
      retinoschisis. Posterior wall masses are usually tumors (eg, melanoma,
      metastasis, nevus, hemangioma) but may also result from subretinal hemorrhage or
      granulomas (from tuberculosis or histoplasmosis). Calcifications may be caused by
      drusen or be nonspecific. Foreign bodies may also be seen. Knowledge of ocular US
      techniques and protocols and familiarity with normal and pathologic imaging
      findings are critical in making a correct diagnosis.

PMID- 22977038
TI  - Multidetector CT and postprocessing in planning and assisting in minimally
      invasive bronchoscopic airway interventions.
AB  - A widening spectrum of increasingly advanced bronchoscopic techniques is
      available for the diagnosis and treatment of various bronchopulmonary diseases.
      The evolution of computed tomography (CT)-multidetector CT in particular-has
      paralleled these advances. The resulting development of two-dimensional and three
      dimensional (3D) postprocessing techniques has complemented axial CT
      interpretation in providing more anatomically familiar information to the
      pulmonologist. Two-dimensional techniques such as multiplanar recontructions and
      3D techniques such as virtual bronchoscopy can provide accurate guidance for
      increasing yield in transbronchial needle aspiration and transbronchial biopsy of
      mediastinal and hilar lymph nodes. Sampling of lesions located deeper within the
      lung periphery via bronchoscopic pathways determined at virtual bronchoscopy are
      also increasingly feasible. CT fluoroscopy for real-time image-guided sampling is
      now widely available; electromagnetic navigation guidance is being used in select
      centers but is currently more costly. Minimally invasive bronchoscopic techniques
      for restoring airway patency in obstruction caused by both benign and malignant
      conditions include mechanical strategies such as airway stent insertion and
      ablative techniques such as electrocauterization and cryotherapy. Multidetector
      CT postprocessing techniques provide valuable information for planning and
      surveillance of these treatment methods. In particular, they optimize the
      evaluation of dynamic obstructive conditions such as tracheobronchomalacia,
      especially with the greater craniocaudal coverage now provided by wide-area
      detectors. Multidetector CT also provides planning information for bronchoscopic
      treatment of bronchopleural fistulas and bronchoscopic lung volume reduction for
      carefully selected patients with refractory emphysema.

PMID- 22977039
TI  - End the farce; a new approach to authorship.

PMID- 22977040
TI  - Regional systems of care after out-of-hospital cardiac arrest in the UK: premier
      league care saves lives.

PMID- 22977041
TI  - Evidence for health policy in India: do we have enough data?

PMID- 22977042
TI  - Do cervical cancer data justify human papillomavirus vaccination in India?
      epidemiological data sources and comprehensiveness.

PMID- 22977043
TI  - Should the ideal be the enemy of the good?

PMID- 22977044
TI  - Author's response: HPV vaccination in India.

PMID- 22977045
TI  - Reform of the clinical excellence awards scheme: why are we waiting?

PMID- 22977046
TI  - The Olympics are over. What have we learned about organizing and delivering
      healthcare?

PMID- 22977047
TI  - Why patients need leaders: introducing a ward safety checklist.
AB  - The safety and consistency of the care given to hospital inpatients has recently
      become a particular political and public concern. The traditional 'ward round'
      presents an obvious opportunity for systematically and collectively ensuring that
      proper standards of care are being achieved for individual patients. This paper
      describes the design and implementation of a 'ward safety checklist' that defines
      a set of potential risk factors that should be checked on a daily basis, and
      offers multidisciplinary teams a number of prompts for sharing and clarifying
      information between themselves, and with the patient, during a round. The concept
      of the checklist and the desire to improve ward rounds were well received in many
      teams, but the barriers to adoption were informative about the current culture on
      many inpatient wards. Although the 'multidisciplinary ward round' is widely
      accepted as good practice, the medical and nursing staff in many teams are
      failing to coordinate their workloads well enough to make multidisciplinary
      rounds a working reality. 'Nursing' and 'medical' care on the ward have become
      'de-coupled' and the potential consequences for patient safety and good
      communication are largely self-evident. This problem is further complicated by a
      medical culture which values the primacy of clinical autonomy and as a result can
      be resistant to perceived attempts to 'systematize' medical care through
      instruments such as checklists.

PMID- 22977048
TI  - The human rights of women with intellectual disability.

PMID- 22977049
TI  - Doctors' age at domestic partnership and parenthood: cohort studies.
AB  - OBJECTIVE: To report on doctors' family formation. Design Cohort studies using
      structured questionnaires. Setting UK. Participants Doctors who qualified in
      1988, 1993, 1996, 1999, 2000 and 2002 were followed up. MAIN OUTCOME MEASURES:
      Living with spouse or partner; and doctors' age when first child was born.
      RESULTS: The response to surveys including questions about domestic circumstances
      was 89.8% (20,717/23,077 doctors). The main outcomes - living with spouse or
      partner, and parenthood - varied according to age at qualification. Using the
      modal ages of 23-24 years at qualification, by the age of 24-25 (i.e. in their
      first year of medical work) a much smaller percentage of doctors than the general
      population was living with spouse or partner. By the age of 33, 75% of both women
      and men doctors were living with spouse or partner, compared with 68% of women
      and 61% of men aged 33 in the general population. By the age of 24-25, 2% of
      women doctors and 41% of women in the general population had a child; but women
      doctors caught up with the general population, in this respect, in their 30s. The
      specialty with the highest percentage of women doctors who, aged 35, had children
      was general practice (74%); the lowest was surgery (41%). CONCLUSIONS: Doctors
      are more likely than other people to live with a spouse or partner, and to have
      children, albeit typically at later ages. Differences between specialties in
      rates of motherhood may indicate sacrifice by some women of family in favour of
      career.

PMID- 22977050
TI  - What inspired me?

PMID- 22977051
TI  - Bartolome Hidalgo de Aguero's 16th century, evidence-based challenge to the
      orthodox management of wounds.

PMID- 22977055
TI  - Disseminated tuberculosis in pregnancy unknown to doctors in Western Europe case
      presentation: 'part of the routine study in infertility'.
AB  - Tuberculosis in pregnancy is possibly increasing in Western Europe due to a
      higher incidence in immigrant women from endemic regions. Common in recent
      immigrants. Diagnosis during pregnancy is delayed because the disease is more
      frequently extra-pulmonary with few symptoms and western doctors are no longer
      familiar with signs and symptoms of tuberculosis. We report the case of a 28-year
      old woman presenting in the 13th week of pregnancy with vaginal bleeding,
      respiratory symptoms including persistent coughing and fever since 1 month.
      Diagnosis was delayed because of doubts on taking x-rays during pregnancy, and
      only 6 days after admission chest x-ray and blood-cultures led to diagnose
      miliary tuberculosis. Despite tuberculostatic medication expulsion of an infected
      fetus and placenta occurred. Histological examination of the placenta confirmed
      tuberculosis in the placental tissue.

PMID- 22977056
TI  - Nitrofurantoin-induced microangiopathic haemolytic anaemia and thrombocytopaenia
      in a patient with systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) may develop thrombotic
      thrombocytopaenic purpura (TTP) or TTP-like illness manifested by
      microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction
      between active SLE and TTP is difficult because these entities share similar
      clinical features. Drug-induced TTP caused by an immune-mediated reaction have
      been documented for several drugs. Herein, we report a middle-aged Hispanic woman
      with long-standing SLE, who developed a TTP-like illness characterised by MAHA
      and thrombocytopaenia after exposure to nitrofurantoin. The patient responded
      well to plasmapheresis and immunosuppressive therapy and has remained clinically
      stable after 18&emsp14;months of follow-up. To our knowledge, this is the first
      case that reports the association between nitrofurantoin and a TTP-like
      presentation.

PMID- 22977057
TI  - Bilateral deep brain stimulation of the nucleus accumbens for comorbid obsessive
      compulsive disorder and Tourette's syndrome.
AB  - We present the case of a 32-year-old Caucasian woman with severe treatment
      refractory obsessive compulsive disorder (OCD) and Tourette's syndrome. Both
      conditions were present prior to age 5 and impacted significantly on the
      patient's functioning. Multiple trials of evidence-based pharmacological and
      behavioural therapies had not achieved remission of symptoms. Bilateral deep
      brain stimulation of the nucleus accumbens was undertaken to treat both illnesses
      but with a particular focus on OCD, as the patient identified this as the more
      debilitating of the two disorders. Following surgery there was an immediate
      improvement in OCD and tic severity. At follow-up 8&emsp14;months later, there
      was a 90% improvement in OCD symptoms and a 57% improvement in tic severity. No
      intraoperative or postoperative complications or adverse events occurred and
      there were no undesired effects of stimulation.

PMID- 22977058
TI  - Cyclosporine-induced haemolytic anaemia in a child with juvenile dermatomyositis.
AB  - Cyclosporine-induced haemolysis is a very rare adverse reaction. The few
      published cases in the literature are described in the context of haemolytic
      uraemic syndrome in transplanted patients. We report a case of cyclosporine
      induced haemolytic anaemia in a 9-year-old girl being treated for severe
      dermatomyositis.

PMID- 22977059
TI  - Gastrobronchial fistula following laparoscopic sleeve gastrectomy.
AB  - Acquired fistulas between the tracheobronchial tree and the gastrointestinal
      tract are rare but serious complications of laparoscopic sleeve gastrectomies
      with significant morbidity and mortality. With the rising popularity and
      widespread acceptance of bariatric surgery techniques, the occurrence of
      gastrobronchial fistulas is being increasingly recognised. We present the case of
      a 26-year-old woman who underwent laparoscopic sleeve gastrectomy for morbid
      obesity and presented later with a history of chronic productive cough. Upper
      gastrointestinal series showed the presence of a communicating fistula between
      the stomach and the lung, with extravasation of contrast into the lung. The aim
      of this paper is to highlight the importance of considering the diagnosis of a
      gastrobronchial fistula in cases of persistent respiratory infections in the
      postoperative period following bariatric surgery and to review its incidence,
      clinical manifestations and treatment.

PMID- 22977060
TI  - Focal adhesion kinase and reactive oxygen species contribute to the persistent
      fibrotic phenotype of lesional scleroderma fibroblasts.
AB  - OBJECTIVE: Fibrotic diseases such as SSc (systemic sclerosis, scleroderma) are
      characterized by the abnormal presence of the myofibroblast, a specialized type
      of fibroblast that overexpresses the highly contractile protein alpha-smooth
      muscle actin. Myofibroblasts display excessive adhesive properties and hence
      exert a potent mechanical force. We aim to identify the precise contribution of
      adhesive signalling, which requires integrin-mediated activation of focal
      adhesion kinase (FAK)/src, to fibrogenic gene expression in normal and fibrotic
      SSc fibroblasts. METHODS: We subject either FAK wild-type and knockout
      fibroblasts or normal and SSc fibroblasts treated with FAK/src inhibitors to real
      time polymerase chain, western blot, cell migration and collagen gel contraction
      analyses. RESULTS: FAK operates downstream of both integrin beta1 and reactive
      oxygen species (ROS) to promote the expression of genes involved in matrix
      production and remodelling, including CCN2, alpha-smooth muscle actin and type I
      collagen. Blocking either FAK/src with PP2 or ROS with N-acetyl cysteine
      alleviates the elevated contractile and migratory capability of lesional SSc
      dermal fibroblasts. CONCLUSIONS: Excessive adhesive signalling is intimately
      involved with the fibrotic phenotype of lesional SSc fibroblasts; blocking
      adhesive signalling or ROS generation may be beneficial in controlling the
      fibrosis observed in SSc.

PMID- 22977061
TI  - Comment on: Tocilizumab treatment in a patient suffering from rheumatoid
      arthritis and concomitant chronic hepatitis C infection.

PMID- 22977062
TI  - Bioethical dilemmas of assisted reproduction in the opinions of Polish women in
      infertility treatment: a research report.
AB  - Infertility Accepted treatment is replete with bioethical dilemmas regarding the
      limits of available medical therapies. Poland has no legal acts regulating the
      ethical problems associated with infertility treatment and work on such
      legislation has been in progress for a long time, arousing very intense emotions
      in Polish society. The purpose of the present study was to find out what Polish
      women undergoing infertility treatment think about the most disputable and
      controversial bioethical problems of assisted reproduction. An Attitudes towards
      Bioethical Problems of Infertility Scale was constructed specifically for this
      study. Items were taken from the Bioethics Bills currently under discussion in
      Polish Parliament (Seym). 312 women were enrolled in the study. Women
      experiencing infertility favoured more liberal legislation. Participants
      disagreed, for example, with the following regulations: prohibition of embryo
      freezing, prohibition of preimplantation genetic diagnosis of embryos, age limits
      for women using in vitro fertilisation and prohibition of in vitro fertilisation
      for single women. The opinions of patients undergoing infertility treatment are
      an important voice in the Polish debate on the Bioethics Bills.

PMID- 22977063
TI  - Delayed cortical development in fetuses with complex congenital heart disease.
AB  - Neurologic impairment is a major complication of complex congenital heart disease
      (CHD). A growing body of evidence suggests that neurologic dysfunction may be
      present in a significant proportion of this high-risk population in the early
      newborn period prior to surgical interventions. We recently provided the first
      evidence that brain growth impairment in fetuses with complex CHD has its origins
      in utero. Here, we extend these observations by characterizing global and
      regional brain development in fetuses with hypoplastic left heart syndrome
      (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance
      imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and
      30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a
      progressive third trimester fall-off in cortical gray and white matter volumes (P
      < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS.
      Significant delays in cortical gyrification were also evident in HLHS fetuses (P
      < 0.001). In the HLHS fetus, local cortical folding delays were detected as early
      as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions
      and appear to precede volumetric brain growth disturbances, which may be an early
      marker of elevated risk for third trimester brain growth failure. 

PMID- 22977064
TI  - Performance and palliative care: a drama module for medical students.
AB  - This paper describes an innovative 2 weeks module for medical students
      facilitated by drama educators and a palliative medicine doctor. The module
      incorporates drama, end-of-life care, teamwork and reflective practice. The
      module contents, practical aspects of drama teaching and learning outcomes are
      discussed. Various themes emerged from a study of Harold Pinter's play, The
      Caretaker, which were relevant to clinical practice: silence, power,
      communication, uncertainty and unanswered questions. Drama teaching may be one
      way of enhancing students' confidence, increasing self- awareness, developing
      ethical thinking and fostering teamworking.

PMID- 22977065
TI  - Genetic analysis of chemosensory traits in human twins.
AB  - We explored genetic influences on the perception of taste and smell stimuli.
      Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride,
      citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium
      chloride, calcium chloride, cinnamon, androstenone, GalaxolideTM, cilantro, and
      basil. For most traits, individual differences were stable over time and some
      traits were heritable (h(2) from 0.41 to 0.71). Subjects were genotyped for 44
      single nucleotide polymorphisms within and near genes related to taste and smell.
      The results of these association analyses confirmed previous  genotype-phenotype
      results for PTC, quinine, and androstenone. New associations were detected for
      ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro
      and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol
      was related to variation within an olfactory receptor gene (OR7D4) and a gene
      encoding a subunit of the epithelial sodium channel (SCNN1D). Our study
      demonstrates that person-to-person differences in the taste and smell perception
      of simple foods and drinks are partially accounted for by genetic variation
      within chemosensory pathways.

PMID- 22977066
TI  - Endosymbiotic bacteria as a source of carotenoids in whiteflies.
AB  - Although carotenoids serve important biological functions, animals are generally
      unable to synthesize these pigments and instead obtain them from food. However,
      many animals, such as sap-feeding insects, may have limited access to carotenoids
      in their diet, and it was recently shown that aphids have acquired the ability to
      produce carotenoids by lateral transfer of fungal genes. Whiteflies also contain
      carotenoids but show no evidence of the fungus-derived genes found in aphids.
      Because many sap-feeding insects harbour intracellular bacteria, it has long been
      hypothesized that these endosymbionts could serve as an alternative source of
      carotenoid biosynthesis. We sequenced the genome of the obligate bacterial
      endosymbiont Portiera from the whitefly Bemisia tabaci. The genome exhibits
      typical signatures of obligate endosymbionts in sap-feeding insects, including
      extensive size reduction (358.2 kb) and enrichment for genes involved in
      essential amino acid biosynthesis. Unlike other sequenced insect endosymbionts,
      however, Portiera has bacterial homologues of the fungal carotenoid biosynthesis
      genes in aphids. Therefore, related lineages of sap-feeding insects appear to
      have convergently acquired the same functional trait by distinct evolutionary
      mechanisms-bacterial endosymbiosis versus fungal lateral gene transfer.

PMID- 22977067
TI  - Evolution of gliding in Southeast Asian geckos and other vertebrates is
      temporally congruent with dipterocarp forest development.
AB  - Gliding morphologies occur in diverse vertebrate lineages in Southeast Asian
      rainforests, including three gecko genera, plus frogs, snakes, agamid lizards and
      squirrels. It has been hypothesized that repeated evolution of gliding is related
      to the dominance of Asian rainforest tree floras by dipterocarps. For
      dipterocarps to have influenced the evolution of gliding in Southeast Asian
      vertebrates, gliding lineages must have Eocene or later origins. However,
      divergence times are not known for most lineages. To investigate the temporal
      pattern of Asian gliding vertebrate evolution, we performed phylogenetic and
      molecular clock analyses. New sequence data for geckos incorporate exemplars of
      each gliding genus (Cosymbotus, Luperosaurus and Ptychozoon), whereas analyses of
      other vertebrate lineages use existing sequence data. Stem ages of most gliding
      vertebrates, including all geckos, cluster in the time period when dipterocarps
      came to dominate Asian tropical forests. These results demonstrate that a
      gliding/dipterocarp correlation is temporally viable, and caution against the
      assumption of early origins for apomorphic taxa.

PMID- 22977068
TI  - Retention of ice-associated amphipods: possible consequences for an ice-free
      Arctic Ocean.
AB  - Recent studies predict that the Arctic Ocean will have ice-free summers within
      the next 30 years. This poses a significant challenge for the marine organisms
      associated with the Arctic sea ice, such as marine mammals and, not least, the
      ice-associated crustaceans generally considered to spend their entire life on the
      underside of the Arctic sea ice. Based upon unique samples collected within the
      Arctic Ocean during the polar night, we provide a new conceptual understanding of
      an intimate connection between these under-ice crustaceans and the deep Arctic
      Ocean currents. We suggest that downwards vertical migrations, followed by
      polewards transport in deep ocean currents, are an adaptive trait of ice fauna
      that both increases survival during ice-free periods of the year and enables re
      colonization of sea ice when they ascend within the Arctic Ocean. From an
      evolutionary perspective, this may have been an adaptation allowing success in a
      seasonally ice-covered Arctic. Our findings may ultimately change the perception
      of ice fauna as a biota imminently threatened by the predicted disappearance of
      perennial sea ice.

PMID- 22977069
TI  - On the evolution of noise-dependent vocal plasticity in birds.
AB  - Signal plasticity is considered an important step in the evolution of animal
      communication. In acoustic communication, signal transmission is often
      constrained by background noise. One adaptation to evade acoustic signal masking
      is the Lombard effect, in which an animal increases its vocal amplitude in
      response to an increase in background noise. This form of signal plasticity has
      been found in mammals, including humans, and some birds, but not frogs. However,
      the evolution of the Lombard effect is still unclear. Here we demonstrate for the
      first time the Lombard effect in a phylogentically basal bird species, the
      tinamou Eudromia elegans. By doing so, we take a step towards reconstructing the
      evolutionary history of noise-dependent vocal plasticity in birds. Similar to
      humans, the tinamous also raised their vocal pitch in noise, irrespective of any
      release from signal masking. The occurrence of the Lombard effect in a basal bird
      group suggests that this form of vocal plasticity was present in the common
      ancestor of all living birds and thus evolved at least as early as 119 Ma.

PMID- 22977070
TI  - Causes of hatching failure in endangered birds.
AB  - About 10 per cent of birds' eggs fail to hatch, but the incidence of failure can
      be much higher in endangered species. Most studies fail to distinguish between
      infertility (due to a lack of sperm) and embryo mortality as the cause of
      hatching failure, yet doing so is crucial in order to understand the underlying
      problem. Using newly validated techniques to visualize sperm and embryonic
      tissue, we assessed the fertility status of unhatched eggs of five endangered
      species, including both wild and captive birds. All eggs were classified as
      'infertile' when collected, but most were actually fertile with numerous sperm on
      the ovum. Eggs of captive birds had fewer sperm and were more likely to be
      infertile than those of wild birds. Our findings raise important questions
      regarding the management of captive breeding programmes.

PMID- 22977071
TI  - Facultative parthenogenesis discovered in wild vertebrates.
AB  - Facultative parthenogenesis (FP)-asexual reproduction by bisexual species-has
      been documented in a variety of multi-cellular organisms but only recently in
      snakes, varanid lizards, birds and sharks. Unlike the approximately 80 taxa of
      unisexual reptiles, amphibians and fishes that exist in nature, FP has yet to be
      documented in the wild. Based on captive documentation, it appears that FP is
      widespread in squamate reptiles (snakes, lizards and amphisbaenians), and its
      occurrence in nature seems inevitable, yet the task of detecting FP in wild
      individuals has been deemed formidable. Here we show, using microsatellite DNA
      genotyping and litter characteristics, the first cases of FP in wild-collected
      pregnant females and their offspring of two closely related species of North
      American pitviper snakes-the copperhead (Agkistrodon contortrix) and cottonmouth
      (Agkistrodon piscivorus). Our findings support the view that non-hybrid origins
      of parthenogenesis, such as FP, are more common in squamates than previously
      thought. With this confirmation, FP can no longer be viewed as a rare curiosity
      outside the mainstream of vertebrate evolution. Future research on FP in squamate
      reptiles related to proximate control of induction, reproductive competence of
      parthenogens and population genetics modelling is warranted.

PMID- 22977072
TI  - The lack of routine surveillance of Parvovirus B19 infection in pregnancy
      prevents an accurate understanding of this regular cause of fetal loss and the
      risks posed by occupational exposure.
AB  - In Europe, fetal loss due to Parvovirus B19 (B19V) is under-reported and a poorly
      addressed occupational risk to pregnant women. This is exemplified
      internationally, where it was unmentioned in the last two European Centre for
      Disease Prevention and Control (ECDC) annual surveillance reports or its 2009
      special report on infections in pregnancy. To assess this potential for
      underestimating B19V fetal loss in pregnancy, we undertook a systematic review of
      practice in Northern Ireland in the management and reporting of B19V infections
      over a 12-month period of heightened transmission, one of six observed in a span
      of 9 years. Pregnant and non-pregnant women presented with symptomatic infection
      in 24 and 93 % of confirmed B19V infections, respectively, with no difference in
      viral loads. There was underinvestigation of viral causes of fetal loss, with
      only 143/2739 (5 %) tested for B19V, and a failure to follow up most non-immune
      women tested following rash contact. Occupational exposure was recorded in 31/60
      (51.6 %) of pregnancies audited following rash exposure, the majority teachers or
      day care workers. Against a background seroprevalence of 66.5 % immunity in women
      of child-bearing years, two patterns of infection were identified. Firstly,
      pregnant women investigated for a rash or exposure to slapped cheek syndrome,
      where an infection incidence of 18 % was observed, resulted in 42 confirmed
      infections, all proceeding to healthy term deliveries. Secondly, pregnant women
      with unsuspected infection had six cases of confirmed B19V fetal loss, including
      four of 22 (18 %) diagnosed at autopsy, of which three were non-hydropic. While
      many studies have reported B19V fetal loss in pregnancy, there are no robust
      public health surveillance figures to draw on. That all six confirmed fetal
      losses came from the small number of miscarriages/stillbirths investigated, 143
      out of 2739, suggests inadequate follow-up of those pregnancies where B19V
      related fetal loss may be most common, and supports the need for enhanced
      surveillance pilots to address this significant gap in public health knowledge.

PMID- 22977074
TI  - Clostridium tetani bacteraemia.
AB  - Tetanus is a neuromuscular disease in which Clostridium tetani exotoxin
      (tetanospasmin) produces muscle spasms, incapacitating its host. To our
      knowledge, C. tetani bacteraemia has never been reported in the literature. The
      ideal management of this entity remains unresolved given that there is no
      literature to guide the therapy.

PMID- 22977073
TI  - Genetic characteristics of drug-resistant Vibrio cholerae O1 causing endemic
      cholera in Dhaka, 2006-2011.
AB  - Vibrio cholerae O1 biotype El Tor (ET), causing the seventh cholera pandemic, was
      recently replaced in Bangladesh by an altered ET possessing ctxB of the Classical
      (CL) biotype, which caused the first six cholera pandemics. In the present study,
      V. cholerae O1 strains associated with endemic cholera in Dhaka between 2006 and
      2011 were analysed for major phenotypic and genetic characteristics. Of 54
      representative V. cholerae isolates tested, all were phenotypically ET and showed
      uniform resistance to trimethoprim/sulfamethoxazole (SXT) and furazolidone (FR).
      Resistance to tetracycline (TE) and erythromycin (E) showed temporal fluctuation,
      varying from year to year, while all isolates were susceptible to gentamicin (CN)
      and ciprofloxacin (CIP). Year-wise data revealed erythromycin resistance to be
      33.3 % in 2006 and 11 % in 2011, while tetracycline resistance accounted for 33,
      78, 0, 100 and 27 % in 2006, 2007, 2008, 2009 and 2010, respectively;
      interestingly, all isolates tested were sensitive to TE in 2011, as observed in
      2008. All V. cholerae isolates tested possessed genetic elements such as SXT,
      ctxAB, tcpA(ET), rstR(ET) and rtxC; none had IntlI (Integron I). Double mismatch
      amplification mutation assay (DMAMA)-PCR followed by DNA sequencing and analysis
      of the ctxB gene revealed a point mutation at position 58 (C->A), which has
      resulted in an amino acid substitution from histidine (H) to asparagine (N) at
      position 20 (genotype 7) since 2008. Although the multi-resistant strains having
      tetracycline resistance showed minor genetic divergence, V. cholerae strains were
      clonal, as determined by a PFGE (NotI)-based dendrogram. This study shows 2008
      2010 to be the time of transition from ctxB genotype 1 to genotype 7 in V.
      cholerae ET causing endemic cholera in Dhaka, Bangladesh.

PMID- 22977075
TI  - Evaluation of the genetic diversity of Histoplasma capsulatum var. capsulatum
      isolates from north-eastern Brazil.
AB  - Since the beginning of the HIV epidemic, there has been a significant increase in
      the number of histoplasmosis cases in Ceara, a state in north-east Brazil. The
      lack of epidemiological data on the genotypes circulating in the north-east
      region shows the importance of more detailed studies on the molecular
      epidemiology of Histoplasma capsulatum var. capsulatum in this region. Different
      molecular techniques have been used to better characterize the genetic profile of
      H. capsulatum var. capsulatum strains. The aim of this study was to analyse the
      genetic diversity of H. capsulatum var. capsulatum isolates in Fortaleza, the
      capital of Ceara, through the sequencing of the internal transcribed spacer
      (ITS)1-5.8S-ITS2 region, and establish the molecular profile of these isolates,
      along with strains from south-east Brazil, by RAPD analysis, featuring the
      different clusters in those regions. The isolates were grouped into two clusters.
      Cluster 1 included strains from the south-east and north-east regions with
      separation of isolates into three distinct subgroups (subgroups 1a, 1b and 1c).
      Cluster 2 included only samples from north-east Brazil. Sequencing of the ITS1
      5.8S-ITS2 region allowed the detection of two major clades, which showed
      geographical correlation between them and their subgroups. Therefore, it can be
      concluded that the H. capsulatum var. capsulatum isolates from Ceara have a high
      degree of genetic polymorphism. The molecular data also confirm that populations
      of this fungus are composed of different genotypes in Brazil and worldwide.

PMID- 22977076
TI  - Proteomic analysis of the response of Listeria monocytogenes to bile salts under
      anaerobic conditions.
AB  - Listeria monocytogenes is a food-borne pathogen responsible for the disease
      listeriosis. The infectious process depends on survival in the high bile-salt
      conditions encountered throughout the gastrointestinal tract, including the
      gallbladder. However, it is not clear how bile-salt resistance mechanisms are
      induced, especially under physiologically relevant conditions. This study sought
      to determine how the L. monocytogenes strains EGDe (serovar 1/2a), F2365 (serovar
      4a) and HCC23 (serovar 4b) respond to bile salts under anaerobic conditions.
      Changes in the expressed proteome were analysed using multidimensional protein
      identification technology coupled with electrospray ionization tandem mass
      spectrometry. In general, the response to bile salts among the strains tested
      involved significant alterations in the presence of cell-wall-associated
      proteins, DNA repair proteins, protein folding chaperones and oxidative stress
      response proteins. Strain viability correlated with an initial osmotic stress
      response, yet continued survival for EGDe and F2365 involved different
      mechanisms. Specifically, proteins associated with biofilm formation in EGDe and
      transmembrane efflux pumps in F2365 were expressed, suggesting that variations
      exist in how virulent strains respond and adapt to high bile-salt environments.
      These results indicate that the bile-salt response varies among these serovars
      and that further research is needed to elucidate how the response to bile salts
      correlates with colonization potential in vivo.

PMID- 22977077
TI  - Microsatellite typing of Aspergillus flavus from clinical and environmental avian
      isolates.
AB  - Aspergillosis is one of the most common causes of death in captive birds.
      Aspergillus fumigatus accounts for approximately 95 % of aspergillosis cases and
      Aspergillus flavus is the second most frequent organism associated with avian
      infections. In the present study, the fungi were grown from avian clinical
      samples (post-mortem lung material) and environmental samples (eggs, food and
      litter). Microsatellite markers were used to type seven clinical avian isolates
      and 22 environmental isolates of A. flavus. A. flavus was the only species (28 %
      prevalence) detected in the avian clinical isolates, whereas this species ranked
      third (19 %) after members of the genera Penicillium (39 %) and Cladosporium (21
      %) in the environmental samples. Upon microsatellite analysis, five to eight
      distinct alleles were detected for each marker. The marker with the highest
      discriminatory power had eight alleles and a 0.852 D value. The combination of
      all six markers yielded a 0.991 D value with 25 distinct genotypes. One clinical
      avian isolate (lung biopsy) and one environmental isolate (egg) shared the same
      genotype. Microsatellite typing of A. flavus grown from avian and environmental
      samples displayed an excellent discriminatory power and 100 % reproducibility.
      This study showed a clustering of clinical and environmental isolates, which were
      clearly separated. Based upon these results, aspergillosis in birds may be
      induced by a great diversity of isolates.

PMID- 22977078
TI  - L-Leucine alleviates Diamond-Blackfan anemia.

PMID- 22977079
TI  - B-cell lymphomas: getting in the zone!

PMID- 22977081
TI  - A promising new biologic prognostic model in diffuse large B-cell lymphoma.

PMID- 22977080
TI  - CD277 takes the lead in human gammadelta T-cell activation.

PMID- 22977082
TI  - Zebrafish lead the way in control of vascular permeability.

PMID- 22977083
TI  - CD146: a new partner for VEGFR2.

PMID- 22977084
TI  - What counts most in the lymph node count for colorectal cancer?
AB  - The adequate number of lymph nodes that should be examined to correctly stage
      colorectal cancer is still debated. Even though the guidelines state that 12
      should be the minimum, there is ongoing concern that this might not be enough.
      Moreover, many studies have shown that this cut-off is far from universally
      obtained in many surgical series, whether via laparotomy or via laparoscopy.
      Arguments in favor of sticking to the cutoff value of 12 are weak: certainly,
      culling and examining as many lymph nodes as possible should increase the chances
      of correct staging and the consequent therapeutic consequences, decrease local
      recurrence and, perhaps, also increase survival (although this is not the direct
      consequence of gathering and examining as many lymph nodes as possible).
      Laparoscopy should be no different from open surgery: the same rational prevails
      for laparoscopic oncologic clearance to increase patient well-being and ensure
      good practice. What is most important, however, is to make surgeons and
      pathologists realize that this issue is important and that all of us should
      strive, in close collaboration, to achieve these goals, for the good of the
      patient, the person for whom the lymph node count counts most.

PMID- 22977085
TI  - STEPS to POEM: introduction of a new technique at the IRCAD.
AB  - The future of natural orifice transluminal endoscopic surgery lies not just in
      the reduction of the invasiness of selected surgical procedures, but more in the
      development of innovative surgical concepts and revisitation of old surgical
      dogmas. This is particularly true for minimally invasive oesophageal surgery
      which is still relatively new and therefore an ideal field for improvement as it
      presents many unanswered questions. Endoluminal and transluminal esophageal
      endoscopic procedures for both diagnostic and therapeutic purposes have recently
      been explored. Most impressively perhaps Haruhiro Inoue{H. Inoue, 2010 #191}, has
      recently reported the first clinical experience of submucosal endoscopic
      esophageal myotomy for esophageal achalasia with a peroral endoscopic myotomy
      (POEM). In addition to being a no-scar technique the true innovation and appeal
      of the POEM procedure is that it specifically targets the circular muscle layers
      of the LES affected by achalasia, thereby preserving the anatomic integrity of
      the LES anatomy and possibly minimizing surgical side effects such as
      gastroesophageal reflux. However, the low incidence of in combination with POEM
      technical demands makes the design of a pathway to introduce this into clinical
      practice a challenge. We describe our recommendations for starting a POEM program
      based on our own experience and describe the first clinical case of POEM
      performed at the University of Strasbourg, as well as being the first in France,
      to illusa model for other institutions wishing to introduce POEM into their
      clinical repertory.

PMID- 22977086
TI  - Innovative surgical techniques of Aspasia, the early Greek gynecologist.

PMID- 22977087
TI  - Pythium oligandrum: an example of opportunistic success.
AB  - Pythium oligandrum, a non-pathogenic soil-inhabiting oomycete, colonizes the root
      ecosystem of many crop species. Whereas most members in the genus Pythium are
      plant pathogens, P. oligandrum distinguishes itself from the pathogenic species
      by its ability to protect plants from biotic stresses in addition to promoting
      plant growth. The success of P. oligandrum at controlling soilborne pathogens is
      partly associated with direct antagonism mediated by mycoparasitism and
      antimicrobial compounds. Interestingly, P. oligandrum has evolved with specific
      mechanisms to attack its prey even when these belong to closely related species.
      Of particular relevance is the question of how P. oligandrum distinguishes
      between self- and non-self cell wall degradation during the mycoparasitic process
      of pathogenic oomycete species. The ability of P. oligandrum to enter and
      colonize the root system before rapidly degenerating is one of the most striking
      features that differentiate it from all other known biocontrol fungal agents. In
      spite of this atypical behaviour, P. oligandrum sensitizes the plant to defend
      itself through the production of at least two types of microbe-associated
      molecular patterns, including oligandrin and cell wall protein fractions, which
      appear to be closely involved in the early events preceding activation of the
      jasmonic acid- and ethylene-dependent signalling pathways and subsequent
      localized and systemic induced resistance. The aim of this review is to highlight
      the expanding knowledge of the mechanisms by which P. oligandrum provides
      beneficial effects to plants and to explore the potential use of this oomycete or
      its metabolites as new disease management strategies.

PMID- 22977088
TI  - Predatory activity of Myxococcus xanthus outer-membrane vesicles and properties
      of their hydrolase cargo.
AB  - The deltaproteobacterium Myxococcus xanthus predates upon members of the soil
      microbial community by secreting digestive factors and lysing prey cells. Like
      other Gram-negative bacteria, M. xanthus produces outer membrane vesicles (OMVs),
      and we show here that M. xanthus OMVs are able to kill Escherichia coli cells.
      The OMVs of M. xanthus were found to contain active proteases, phosphatases,
      other hydrolases and secondary metabolites. Alkaline phosphatase activity was
      found to be almost exclusively associated with OMVs, implying that there is
      active targeting of phosphatases into OMVs, while other OMV components appear to
      be packaged passively. The kinetic properties of OMV alkaline phosphatase suggest
      that there may have been evolutionary adaptation of OMV enzymes to a relatively
      indiscriminate mode of action, consistent with a role in predation. In addition,
      the observed regulation of production, and fragility of OMV activity, may protect
      OMV-producing cells from exploitation by M. xanthus cheating genotypes and/or
      other competitors. Killing of E. coli by M. xanthus OMVs was enhanced by the
      addition of a fusogenic enzyme (glyceraldehyde-3-phosphate dehydrogenase; GAPDH),
      which triggers fusion of vesicles with target membranes within eukaryotic cells.
      This suggests that the mechanism of prey killing involves OMV fusion with the E.
      coli outer membrane. M. xanthus secretes GAPDH, which could potentially modulate
      the fusion of co-secreted OMVs with prey organisms in nature, enhancing their
      predatory activity.

PMID- 22977089
TI  - Substitutions in the Escherichia coli RNA polymerase inhibitor T7 Gp2 that allow
      inhibition of transcription when the primary interaction interface between Gp2
      and RNA polymerase becomes compromised.
AB  - The Escherichia coli-infecting bacteriophage T7 encodes a 7 kDa protein, called
      Gp2, which is a potent inhibitor of the host RNA polymerase (RNAp). Gp2 is
      essential for T7 phage development. The interaction site for Gp2 on the E. coli
      RNAp is the beta' jaw domain, which is part of the DNA binding channel. The
      binding of Gp2 to the beta' jaw antagonizes several steps associated with
      interactions between the RNAp and promoter DNA, leading to inhibition of
      transcription at the open promoter complex formation step. In the structure of
      the complex formed between Gp2 and a fragment of the beta' jaw, amino acid
      residues in the beta3 strand of Gp2 contribute to the primary interaction
      interface with the beta' jaw. The 7009 E. coli strain is resistant to T7 because
      it carries a charge reversal point mutation in the beta' jaw that prevents Gp2
      binding. However, a T7 phage encoding a mutant form of Gp2, called Gp2(beta),
      which carries triple amino acid substitutions E24K, F27Y and R56C, can
      productively infect this strain. By studying the molecular basis of inhibition of
      RNAp from the 7009 strain by Gp2(beta), we provide several lines of evidence that
      the E24K and F27Y substitutions facilitate an interaction with RNAp when the
      primary interaction interface with the beta' jaw is compromised. The proposed
      additional interaction interface between RNAp and Gp2 may contribute to the
      multipronged mechanism of transcription inhibition by Gp2.

PMID- 22977090
TI  - Expression of Pseudomonas syringae type III effectors in yeast under stress
      conditions reveals that HopX1 attenuates activation of the high osmolarity
      glycerol MAP kinase pathway.
AB  - The Gram-negative bacterium Pseudomonas syringae pv. tomato (Pst) is the causal
      agent of speck disease in tomato. Pst pathogenicity depends on a type III
      secretion system that delivers effector proteins into host cells, where they
      promote disease by manipulating processes to the advantage of the pathogen.
      Previous studies identified seven Pst effectors that inhibit growth when
      expressed in yeast under normal growth conditions, suggesting that they interfere
      with cellular processes conserved in yeast and plants. We hypothesized that
      effectors also target conserved cellular processes that are required for yeast
      growth only under stress conditions. We therefore examined phenotypes induced by
      expression of Pst effectors in yeast grown in the presence of various stressors.
      Out of 29 effectors tested, five (HopX1, HopG1, HopT1-1, HopH1 and AvrPtoB)
      displayed growth inhibition phenotypes only in combination with stress
      conditions. Viability assays revealed that the HopX1 effector caused loss of cell
      viability under prolonged osmotic stress. Using transcription reporters, we found
      that HopX1 attenuated the activation of the high osmolarity glycerol (HOG)
      mitogen-activated protein kinase (MAPK) pathway, which is responsible for yeast
      survival under osmotic stress, while other MAPK pathways were mildly affected by
      HopX1. Interestingly, HopX1-mediated phenotypes in yeast were dependent on the
      putative transglutaminase catalytic triad of the effector. This study enlarges
      the pool of phenotypes available for the functional analysis of Pst type III
      effectors in yeast, and exemplifies how analysis of phenotypes detected in yeast
      under stress conditions can lead to the identification of eukaryotic cellular
      processes affected by bacterial effectors.

PMID- 22977091
TI  - Cord factors from atypical mycobacteria (Mycobacterium alvei, Mycobacterium
      brumae) stimulate the secretion of some pro-inflammatory cytokines of relevance
      in tuberculosis.
AB  - The ability to induce several cytokines relevant to tuberculosis (TNF-alpha, IL
      1beta, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from
      Mycobacterium alvei CR-21(T) and Mycobacterium brumae CR-270(T) was studied in
      the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor
      from Mycobacterium tuberculosis H37Rv, where this glycolipid appears to be
      implicated in the pathogenesis of tuberculosis. Details of the fine structure of
      these molecules were obtained by NMR and MS. The mycoloyl residues were
      identified as alpha and (omega-1)-methoxy in M. alvei CR-21(T) and alpha in M.
      brumae CR-270(T); in both cases they were di-unsaturated instead of
      cyclopropanated as found in M. tuberculosis. In RAW 264.7 cells, cord factors
      from M. alvei CR-21(T), M. brumae CR-270(T) and M. tuberculosis differed in their
      ability to stimulate IL-6, the higher levels corresponding to the cord factor
      from M. tuberculosis. In THP-1 cells, a similar overall profile of cytokines was
      found for M. alvei CR-21(T) and M. brumae CR-270(T), with high proportions of IL
      1beta and TNF-alpha, and different from M. tuberculosis, where IL-6 and IL-12p40
      prevailed. The data obtained indicate that cord factors from the atypical
      mycobacteria M. alvei CR-21(T) and M. brumae CR-270(T) stimulated the secretion
      of several pro-inflammatory cytokines, although there were some differences with
      those of M. tuberculosis H37Rv. This finding seems to be due to their particular
      mycoloyl substituents and could be of interest when considering the potential
      adjuvanticity of these molecules.

PMID- 22977096
TI  - Analytical investigation of self-organized criticality in neural networks.
AB  - Dynamical criticality has been shown to enhance information processing in
      dynamical systems, and there is evidence for self-organized criticality in neural
      networks. A plausible mechanism for such self-organization is activity-dependent
      synaptic plasticity. Here, we model neurons as discrete-state nodes on an
      adaptive network following stochastic dynamics. At a threshold connectivity, this
      system undergoes a dynamical phase transition at which persistent activity sets
      in. In a low-dimensional representation of the macroscopic dynamics, this
      corresponds to a transcritical bifurcation. We show analytically that adding
      activity-dependent rewiring rules, inspired by homeostatic plasticity, leads to
      the emergence of an attractive steady state at criticality and present numerical
      evidence for the system's evolution to such a state.

PMID- 22977097
TI  - Multiwalled carbon nanotubes in alfalfa and wheat: toxicology and uptake.
AB  - Data on the bioavailability and toxicity of carbon nanotubes (CNTs) in the
      environment, and, in particular, on their interactions with vascular plants, are
      limited. We investigated the effects of industrial-grade multiwalled CNTs (75 wt%
      CNTs) and their impurities on alfalfa and wheat. Phytotoxicity assays were
      performed during both seed germination and seedling growth. The germinations of
      both species were tolerant of up to 2560 mg l(-1) CNTs, and root elongation was
      enhanced in alfalfa and wheat seedlings exposed to CNTs. Remarkably, catalyst
      impurities also enhanced root elongation in alfalfa seedlings as well as wheat
      germination. Thus the impurities, not solely the CNTs, impacted the plants. CNT
      internalization by plants was investigated using electron microscopy and two
      dimensional Raman mapping. The latter showed that CNTs were adsorbed onto the
      root surfaces of alfalfa and wheat without significant uptake or translocation.
      Electron microscopy investigations of internalization were inconclusive owing to
      poor contrast, so Fe(3)O(4)-functionalized CNTs were prepared and studied using
      energy-filter mapping of Fe(3)O(4). CNTs bearing Fe(3)O(4) nanoparticles were
      detected in the epidermis of one wheat root tip only, suggesting that
      internalization was possible but unusual. Thus, alfalfa and wheat tolerated high
      concentrations of industrial-grade multiwalled CNTs, which adsorbed onto their
      roots but were rarely taken up.

PMID- 22977098
TI  - What do molecules do when we are not looking? State sequence analysis for
      stochastic chemical systems.
AB  - Many biomolecular systems depend on orderly sequences of chemical transformations
      or reactions. Yet, the dynamics of single molecules or small-copy-number
      molecular systems are significantly stochastic. Here, we propose state sequence
      analysis--a new approach for predicting or visualizing the behaviour of
      stochastic molecular systems by computing maximum probability state sequences,
      based on initial conditions or boundary conditions. We demonstrate this approach
      by analysing the acquisition of drug-resistance mutations in the human
      immunodeficiency virus genome, which depends on rare events occurring on the time
      scale of years, and the stochastic opening and closing behaviour of a single
      sodium ion channel, which occurs on the time scale of milliseconds. In both
      cases, we find that our approach yields novel insights into the stochastic
      dynamical behaviour of these systems, including insights that are not correctly
      reproduced in standard time-discretization approaches to trajectory analysis.

PMID- 22977099
TI  - Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional
      scaffolds: an improved in vitro tumour model.
AB  - Owing to the reduced co-relationship between conventional flat Petri dish culture
      (two-dimensional) and the tumour microenvironment, there has been a shift towards
      three-dimensional culture systems that show an improved analogy to the same. In
      this work, an extracellular matrix (ECM)-mimicking three-dimensional scaffold
      based on chitosan and gelatin was fabricated and explored for its potential as a
      tumour model for lung cancer. It was demonstrated that the chitosan-gelatin (CG)
      scaffolds supported the formation of tumoroids that were similar to tumours grown
      in vivo for factors involved in tumour-cell-ECM interaction, invasion and
      metastasis, and response to anti-cancer drugs. On the other hand, the two
      dimensional Petri dish surfaces did not demonstrate gene-expression profiles
      similar to tumours grown in vivo. Further, the three-dimensional CG scaffolds
      supported the formation of tumoroids, using other types of cancer cells such as
      breast, cervix and bone, indicating a possible wider potential for in vitro
      tumoroid generation. Overall, the results demonstrated that CG scaffolds can be
      an improved in vitro tool to study cancer progression and drug screening for
      solid tumours.

PMID- 22977100
TI  - Biomimetic surfaces with controlled direction-dependent adhesion.
AB  - We propose a novel design of a biomimetic micro-structured surface, which
      exhibits controlled strongly direction-dependent adhesion properties. The micro
      system consists of parallel elastic wall-like structures covered by a thin layer.
      Numerical calculations have been carried out to study the adhesive properties of
      the proposed system and to provide design criteria with the aim of obtaining
      optimized geometries. A numerically equivalent version of the double cantilever
      beam fracture experiment is, then, simulated by means of finite element analysis
      to investigate the anisotropic adhesion of the structure. We find that, because
      of inherent crack trapping properties of these types of structures, the wall-like
      geometry allows us to strongly enhance adhesion when the detachment direction is
      perpendicular to the walls. On the other hand, when the detachment occurs
      parallel to the walls, the system shows low adhesion. This controlled direction
      dependent adhesive property of the proposed structure solves one of the key
      problems of biomimetic adhesive surfaces, which usually show very strong
      adhesion, even larger than biological systems, but are not suitable for object
      manipulation and locomotion, as detachment always occurs at high loads and cannot
      be controlled.

PMID- 22977101
TI  - Fluctuating noise drives Brownian transport.
AB  - The transport properties of Brownian ratchet were studied in the presence of
      stochastic intensity noise in both overdamped and underdamped regimes. In the
      overdamped case, an analytical solution using the matrix-continued fraction
      method revealed the existence of a maximum current when the noise intensity
      fluctuates on intermediate timescale regions. Similar effects were observed for
      the underdamped case by Monte Carlo simulations. The optimal time-correlation for
      Brownian transport coincided with the experimentally observed time-correlation of
      the extrinsic noise in Escherichia coli gene expression and implied the
      importance of environmental noise for molecular mechanisms.

PMID- 22977102
TI  - Tomographic particle image velocimetry of desert locust wakes: instantaneous
      volumes combine to reveal hidden vortex elements and rapid wake deformation.
AB  - Aerodynamic structures generated by animals in flight are unstable and complex.
      Recent progress in quantitative flow visualization has advanced our understanding
      of animal aerodynamics, but measurements have hitherto been limited to flow
      velocities at a plane through the wake. We applied an emergent, high-speed,
      volumetric fluid imaging technique (tomographic particle image velocimetry) to
      examine segments of the wake of desert locusts, capturing fully three-dimensional
      instantaneous flow fields. We used those flow fields to characterize the
      aerodynamic footprint in unprecedented detail and revealed previously unseen wake
      elements that would have gone undetected by two-dimensional or stereo-imaging
      technology. Vortex iso-surface topographies show the spatio-temporal signature of
      aerodynamic force generation manifest in the wake of locusts, and expose the
      extent to which animal wakes can deform, potentially leading to unreliable
      calculations of lift and thrust when using conventional diagnostic methods. We
      discuss implications for experimental design and analysis as volumetric flow
      imaging becomes more widespread.

PMID- 22977103
TI  - Shape optimization in exoskeletons and endoskeletons: a biomechanics analysis.
AB  - This paper addresses the question of strength and mechanical failure in
      exoskeletons and endoskeletons. We developed a new, more sophisticated model to
      predict failure in bones and other limb segments, modelled as hollow tubes of
      radius r and thickness t. Five failure modes were considered: transverse
      fracture; buckling (of three different kinds) and longitudinal splitting. We also
      considered interactions between failure modes. We tested the hypothesis that
      evolutionary adaptation tends towards an optimum value of r/t, this being the
      value which gives the highest strength (i.e. load-carrying capacity) for a given
      weight. We analysed two examples of arthropod exoskeletons: the crab merus and
      the locust tibia, using data from the literature and estimating the stresses
      during typical activities. In both cases, the optimum r/t value for bending was
      found to be different from that for axial compression. We found that the crab
      merus experiences similar levels of bending and compression in vivo and that its
      r/t value represents an ideal compromise to resist these two types of loading.
      The locust tibia, however, is loaded almost exclusively in bending and was found
      to be optimized for this loading mode. Vertebrate long bones were found to be far
      from optimal, having much lower r/t values than predicted, and in this respect
      our conclusions differ from those of previous workers. We conclude that our
      theoretical model, though it has some limitations, is useful for investigating
      evolutionary development of skeletal form in exoskeletons and endoskeletons.

PMID- 22977104
TI  - Compass magnetoreception in birds arising from photo-induced radical pairs in
      rotationally disordered cryptochromes.
AB  - According to the radical pair model, the magnetic compass sense of migratory
      birds relies on photochemical transformations in the eye to detect the direction
      of the geomagnetic field. Magnetically sensitive radical pairs are thought to be
      generated in cryptochrome proteins contained in magnetoreceptor cells in the
      retina. A prerequisite of the current model is for some degree of rotational
      ordering of both the cryptochromes within the cells and of the cells within the
      retina so that the directional responses of individual molecules do not average
      to zero. Here, it is argued that anisotropic distributions of radical pairs can
      be generated by the photoselection effects that arise from the directionality of
      the light entering the eye. Light-induced rotational order among the transient
      radical pairs rather than intrinsic ordering of their molecular precursors is
      seen as the fundamental condition for a magnetoreceptor cell to exhibit an
      anisotropic response. A theoretical analysis shows that a viable compass
      magnetoreceptor could result from randomly oriented cryptochromes contained in
      randomly oriented cells distributed around the retina.

PMID- 22977105
TI  - Drug eluting stents for patients with diabetes.

PMID- 22977107
TI  - Reasons to be hopeful: streams of renewal in healthcare.

PMID- 22977108
TI  - Medicine and the Media. Statins for all?

PMID- 22977109
TI  - Lansley's legacy.

PMID- 22977110
TI  - German health insurers are urged to pay rebates to members as surplus reaches
      record high.

PMID- 22977111
TI  - New guidance on donating organs is issued amid fears of attempts to profit from
      giving.

PMID- 22977112
TI  - Influence of submission form characteristics on clinical information received in
      biopsy accession.
AB  - Clinical information supplied to diagnostic laboratories through biopsy
      submission forms is crucial to accurate, timely diagnosis and to
      clinicopathologic correlation between microscopic findings and the clinical
      condition of the patient. The current study attempts to quantify the prevalence
      of deficient and inadequate submissions in veterinary biopsy service and to
      determine whether form characteristics, such as the open or closed nature of the
      form and the presence of specific prompts, influence reporting of essential case
      information. The hypotheses of this study are, first, that deficient and
      inadequate biopsy submissions do occur in veterinary medicine and, second, that
      open-type biopsy submission forms elicit quantitatively and qualitatively more
      complete case information overall, and in specific content areas, compared to
      closed-type biopsy submission forms. Three percent of submissions reviewed were
      information deficient, devoid of information beyond patient signalment, and more
      than 88% of forms supplied inadequate clinical information in at least 1 key
      content area. Both form type and specific prompts significantly influenced
      reporting of important clinical information. This study demonstrates the need and
      lays the foundation for informational completeness research in veterinary
      medicine.

PMID- 22977113
TI  - Mortality of a captive axis deer (Axis axis) and a llama (Lama glama) due to
      ingestion of Wedelia glauca.
AB  - The current study describes a naturally occurring cluster of cases of Wedelia
      glauca intoxication. Seven of 14 axis deer (Axis axis) and 1 of 8 llamas (Lama
      glama) in a zoo of Buenos Aires province, Argentina, died suddenly after
      ingestion of a new batch of alfalfa (Medicago sativa) hay bales contaminated with
      the hepatotoxic plant W. glauca. Necropsies of 1 deer and 1 llama were performed.
      Pathological findings in both animals included severe diffuse acute centrilobular
      hepatocellular necrosis and hemorrhage, and clear yellowish translucent
      gelatinous edema on the wall of the gall bladder and the serosa of the
      choledochoduodenal junction. Fragments of W. glauca plants were identified in the
      hay based on the botanical characteristics of the leaves. Samples of gastric
      contents were examined by microhistological analysis, which identified epidermal
      fragments of W. glauca based on the presence of characteristic uniseriate
      glandular hairs (trichomes), confirming recent ingestion of W. glauca in both
      cases. The fragments were quantified and represented 5% of all examined vegetal
      fragments in the deer and 10% in the llama.

PMID- 22977114
TI  - Evolution of conjugation and type IV secretion systems.
AB  - Genetic exchange by conjugation is responsible for the spread of resistance,
      virulence, and social traits among prokaryotes. Recent works unraveled the
      functioning of the underlying type IV secretion systems (T4SS) and its
      distribution and recruitment for other biological processes (exaptation), notably
      pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the
      evolutionary history of conjugation and T4SS. We show that single-stranded DNA
      (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key
      AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key
      ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage
      from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in
      diderm bacteria, possibly Proteobacteria, and then spread to other bacterial
      phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within
      the eight monophyletic groups, determined by both taxonomy and structure of the
      cell envelope. Transfer to monoderms might have occurred only once, but followed
      diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation
      system based on an atypical relaxase and an ATPase derived from a dsDNA
      translocase. The observed evolutionary rates and patterns of presence/absence of
      specific T4SS proteins show that conjugation systems are often and independently
      exapted for other functions. This work brings a natural basis for the
      classification of all kinds of conjugative systems, thus tackling a problem that
      is growing as fast as genomic databases. Our analysis provides the first global
      picture of the evolution of conjugation and shows how a self-transferrable
      complex multiprotein system has adapted to different taxa and often been
      recruited by the host. As conjugation systems became specific to certain clades
      and cell envelopes, they may have biased the rate and direction of gene transfer
      by conjugation within prokaryotes.

PMID- 22977115
TI  - Coevolution reveals a network of human proteins originating with
      multicellularity.
AB  - Protein interaction networks play central roles in biological systems, from
      simple metabolic pathways through complex programs permitting the development of
      organisms. Multicellularity could only have arisen from a careful orchestration
      of cellular and molecular roles and responsibilities, all properly controlled and
      regulated. Disease reflects a breakdown of this organismal homeostasis. To better
      understand the evolution of interactions whose dysfunction may be contributing
      factors to disease, we derived the human protein coevolution network using our
      MatrixMatchMaker algorithm and using the Orthologous MAtrix project (OMA)
      database as a source for protein orthologs from 103 eukaryotic genomes. We
      annotated the coevolution network using protein-protein interaction data, many
      functional data sources, and we explored the evolutionary rates and dates of
      emergence of the proteins in our data set. Strikingly, clustering based only on
      the topology of the coevolution network partitions it into two subnetworks, one
      generally representing ancient eukaryotic functions and the other functions more
      recently acquired during animal evolution. That latter subnetwork is enriched for
      proteins with roles in cell-cell communication, the control of cell division, and
      related multicellular functions. Further annotation using data from genetic
      disease databases and cancer genome sequences strongly implicates these proteins
      in both ciliopathies and cancer. The enrichment for such disease markers in the
      animal network suggests a functional link between these coevolving proteins.
      Genetic validation corroborates the recruitment of ancient cilia in the evolution
      of multicellularity.

PMID- 22977116
TI  - Integrating sequence variation and protein structure to identify sites under
      selection.
AB  - We present a novel method to identify sites under selection in protein-coding
      genes. Our method combines the traditional Goldman-Yang model of coding-sequence
      evolution with the information obtained from the 3D structure of the evolving
      protein, specifically the relative solvent accessibility (RSA) of individual
      residues. We develop a random-effects likelihood sites model in which rate
      classes are RSA dependent. The RSA dependence is modeled with linear functions.
      We demonstrate that our RSA-dependent model provides a significantly better fit
      to molecular sequence data than does a traditional, RSA-independent model. We
      further show that our model provides a natural, RSA-dependent neutral baseline
      for the evolutionary rate ratio omega = dN/dS Sites that deviate from this
      neutral baseline likely experience selection pressure for function. We apply our
      method to the influenza proteins hemagglutinin and neuraminidase. For
      hemagglutinin, our method recovers positively selected sites near the sialic acid
      binding site and negatively selected sites that may be important for
      trimerization. For neuraminidase, our method recovers the oseltamivir resistance
      site and otherwise suggests that few sites deviate from the neutral baseline. Our
      method is broadly applicable to any protein sequences for which structural data
      are available or can be obtained via homology modeling or threading.

PMID- 22977117
TI  - Phylotranscriptomics to bring the understudied into the fold: monophyletic
      ostracoda, fossil placement, and pancrustacean phylogeny.
AB  - An ambitious, yet fundamental goal for comparative biology is to understand the
      evolutionary relationships for all of life. However, many important taxonomic
      groups have remained recalcitrant to inclusion into broader scale studies. Here,
      we focus on collection of 9 new 454 transcriptome data sets from Ostracoda, an
      ancient and diverse group with a dense fossil record, which is often undersampled
      in broader studies. We combine the new transcriptomes with a new morphological
      matrix (including fossils) and existing expressed sequence tag, mitochondrial
      genome, nuclear genome, and ribosomal DNA data. Our analyses lead to new insights
      into ostracod and pancrustacean phylogeny. We obtained support for three epic
      pancrustacean clades that likely originated in the Cambrian: Oligostraca
      (Ostracoda, Mystacocarida, Branchiura, and Pentastomida); Multicrustacea
      (Copepoda, Malacostraca, and Thecostraca); and a clade we refer to as
      Allotriocarida (Hexapoda, Remipedia, Cephalocarida, and Branchiopoda). Within the
      Oligostraca clade, our results support the unresolved question of ostracod
      monophyly. Within Multicrustacea, we find support for Thecostraca plus Copepoda,
      for which we suggest the name Hexanauplia. Within Allotriocarida, some analyses
      support the hypothesis that Remipedia is the sister taxon to Hexapoda, but others
      support Branchiopoda + Cephalocarida as the sister group of hexapods. In multiple
      different analyses, we see better support for equivocal nodes using slow-evolving
      genes or when excluding distant outgroups, highlighting the increased importance
      of conditional data combination in this age of abundant, often anonymous data.
      However, when we analyze the same set of species and ignore rate of gene
      evolution, we find higher support when including all data, more in line with a
      "total evidence" philosophy. By concatenating molecular and morphological data,
      we place pancrustacean fossils in the phylogeny, which can be used for studies of
      divergence times in Pancrustacea, Arthropoda, or Metazoa. Our results and new
      data will allow for attributes of Ostracoda, such as its amazing fossil record
      and diverse biology, to be leveraged in broader scale comparative studies.
      Further, we illustrate how adding extensive next-generation sequence data from
      understudied groups can yield important new phylogenetic insights into long
      standing questions, especially when carefully analyzed in combination with other
      data.

PMID- 22977118
TI  - Evolution of the ARF gene family in land plants: old domains, new tricks.
AB  - Auxin response factors (ARF) are key players in plant development. They mediate
      the cellular response to the plant hormone auxin by activating or repressing the
      expression of downstream developmental genes. The pivotal activation function of
      ARF proteins is enabled by their four-domain architecture, which includes both
      DNA-binding and protein dimerization motifs. To determine the evolutionary origin
      of this characteristic architecture, we built a comprehensive data set of 224 ARF
      related protein sequences that represents all major living divisions of land
      plants, except hornworts. We found that ARFs are split into three subfamilies
      that could be traced back to the origin of the land plants. We also show that
      repeated events of extensive gene duplication contributed to the expansion of
      those three original subfamilies. Further examination of our data set uncovered a
      broad diversity in the structure of ARF transcripts and allowed us to identify an
      additional conserved motif in ARF proteins. We found that additional structural
      diversity in ARF proteins is mainly generated by two mechanisms: genomic
      truncation and alternative splicing. We propose that the loss of domains from the
      canonical, four-domain ARF structure has promoted functional shifts within the
      ARF family by disrupting either dimerization or DNA-binding capabilities. For
      instance, the loss of dimerization domains in some ARFs from moss and spikemoss
      genomes leads to proteins that are reminiscent of Aux/IAA proteins, possibly
      providing a clue on the evolution of these modulators of ARF function. We also
      assessed the functional impact of alternative splicing in the case of ARF4, for
      which we have identified a novel isoform in Arabidopsis thaliana. Genetic
      analysis showed that these two transcripts exhibit markedly different
      developmental roles in A. thaliana. Gene duplications, domain rearrangement, and
      post-transcriptional regulation have thus enabled a subtle control of auxin
      signaling through ARF proteins that may have contributed to the critical
      importance of these regulators in plant development and evolution.

PMID- 22977119
TI  - A green method using a micellar system for determination of andrographolide and
      dehydroandrographolide in human plasma.
AB  - A method based on cloud point extraction (CPE) coupled with high-performance
      liquid chromatography separation and ultraviolet (UV) detection was developed to
      determine andrographolide and dehydroandrographolide in human plasma. The
      nonionic surfactant Triton X-114 was chosen as the extraction medium. Variable
      parameters affecting the CPE efficiency were evaluated and optimized, such as
      concentrations of Triton X-114 and NaCl, pH, equilibration temperature and
      equilibration time. A Zorbax SB C18 column (250 * 4.6 mm i.d., 5 um) was used for
      separation of the two analytes at 30 degrees C. The UV detection was performed at
      254 nm. Under the optimum conditions, the limits of detection of andrographolide
      and dehydroandrographolide are 0.032 and 0.019 ug/mL, respectively. The intra-day
      and inter-day precisions expressed as relative standard deviation ranged from 3.2
      to 7.3% and from 2.9 and 8.6%. The recoveries of andrographolide and
      dehydroandrographolide were in the range of 76.8-98.6% at three fortified
      concentrations of 0.1, 0.5 and 1.0 ug/mL. This method was efficient,
      environmentally friendly, rapid and inexpensive for the extraction and
      determination of andrographolide and dehydroandrographolide in human plasma.

PMID- 22977120
TI  - Determination of 22 ginsenosides in ginseng products using ultra-high-performance
      liquid chromatography.
AB  - A reverse-phase ultra-high-performance liquid chromatography (u-HPLC) method was
      developed for the rapid quantification of 22 ginsenosides in ginseng products.
      The proposed method for the analysis of ginsenosides is based on a heating-block
      method without further treatment. The u-HPLC separation was performed on a
      reversed C18 column (100 * 2 mm id, particle size 2 um) followed by ultraviolet
      detection at 203 nm. Aqueous 50% methanol was used as the extraction solvent. The
      optimum amount of extraction solvent and the optimum extraction time were 20 mL
      and 20 min (extracted twice with 10 mL), respectively. The method validation
      parameters yielded good results for linearity, precision, accuracy and recovery.
      The recovery of ginsenosides from ginseng powder was greater than 98.1% and the
      limits of detection and quantification of the u-HPLC analysis were >0.6 and >1.8
      mg/kg for ginsenosides. The calibration graphs for ginsenosides were linear from
      approximately 2.6 to 40.4 mg/kg for u-HPLC. The inter-day and intra-day
      precisions (relative standard deviation values) were <14.6 and 14.7%, except for
      Rg2(R) + Rh1(R).

PMID- 22977121
TI  - A rapid HPLC method for the simultaneous determination of amiodarone and its
      major metabolite in rat plasma and tissues: a useful tool for pharmacokinetic
      studies.
AB  - A rapid and sensitive high-performance liquid chromatography (HPLC) method was
      developed and validated in rat plasma and tissue (heart, liver, kidney and lung)
      homogenates for the determination of amiodarone and its primary metabolite
      (desethylamiodarone), using tamoxifen as internal standard. Chromatographic
      separation was achieved within less than 5 min on a LiChroCART Purospher Star C18
      column (55 * 4 mm, 3 um). The mobile phase, consisting of phosphate buffer (50
      mM) with 0.1% formic acid (pH 3.1)-methanol-acetonitrile (45:5:50, v/v/v), was
      pumped isocratically at a flow rate of 1.2 mL/min. The detection was conducted at
      254 nm for all compounds. Calibration curves were linear (r(2) >= 0.995) in the
      range of 0.1-15 ug/mL for amiodarone and desethylamiodarone. The limits of
      quantification were established at 0.1 ug/mL for both analytes. The overall data
      of precision and accuracy were in accordance with international guidelines for
      bioanalytical method validation. Amiodarone and desethylamiodarone were extracted
      from rat matrices by a liquid-liquid extraction procedure and the mean recovery
      ranged from 59.9 to 97.6%. This novel HPLC method allows the fast and reliable
      determination of amiodarone and desethylamiodarone from several rat matrices
      (plasma, liver, kidneys, lungs and heart) and was successfully applied in a
      preliminary pharmacokinetic study.

PMID- 22977123
TI  - Pressure on hospitals has led to worse care for older patients.

PMID- 22977122
TI  - Chemical profiling of the Chinese herb formula Xiao-Cheng-Qi Decoction using
      liquid chromatography coupled with electrospray ionization mass spectrometry.
AB  - An approach was established to analyze the chemical profiling of Xiao-Cheng-Qi
      Decoction (XCQD) using liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry. XCQD consisted of three herbal medicines (Rhubarb,
      Fructus Aurantii Immaturus and Cortex Magnoliae Officinalis). The traditional
      water extractive method was applied in the sample preparation, which was
      identical with clinical use. The characteristic fragmentation pathways of 17
      reference compounds were comprehensively studied, including precursors of
      tannins, flavonones, anthraquinones and lignan. In total, 71 constituents were
      identified or tentatively characterized based on their mass spectrometry
      fragmentations and chromatographic behaviors. By comparing their relative
      contents, flavanones and anthraquinones were supposed to be used together for the
      quality control of XCQD. Further pharmacology and pharmacokinetics investigations
      should be performed on the basis of the present chemical profiling study.

PMID- 22977124
TI  - Lives saved by breast screening outnumber cases of overdiagnosis, review says.

PMID- 22977125
TI  - Chemical healthcare waste management in small Brazilian municipalities.
AB  - The disposal of healthcare waste (HCW) seems to have been solved in developed
      countries, while in most developing countries the problem persists because the
      disposal methods are expensive and larger than the budget of small- and medium
      sized municipalities. The current study evaluates the encapsulation process for
      the disposal of medical chemical waste. The experiment was developed in the Pirai
      municipality (Rio de Janeiro State, Brazil) and the chemical wastes were produced
      in the local public hospital, as well as the 12 units of primary care health
      services. Chemical waste generated at health services units may include the
      liquid waste from cleaning materials and disinfectants, expired and unused
      pharmaceutical products, and cytotoxins. These are all considered hazardous waste
      products and they must be disposed of via an authorised system at approved sites
      (e.g. industrial landfills). The process of encapsulating chemical medical waste
      in concrete (cement, crushed stones and sand) followed by their disposal at
      sanitary landfills is a procedure that is not considered in Brazilian
      Legislation. Despite the oversight, this method of disposal was used in the
      municipality of Pirai, with the approval of the Rio de Janeiro State Agency for
      Environmental Control. The safety aspects of this method and the limits of its
      applicability, particularly in small municipalities, were evaluated in this
      study. The results indicate that, within certain parameters, this method may
      provide a viable solution for the disposal of HCW in small municipalities.

PMID- 22977127
TI  - Neonatal seizure: what is the cause?

PMID- 22977126
TI  - Comparison of velocity vector imaging echocardiography with magnetic resonance
      imaging in mouse models of cardiomyopathy.
AB  - BACKGROUND: Myocardial strain imaging using echocardiography can be a cost
      effective method to quantify ventricular wall motion objectively, but few studies
      have compared strain measured with echocardiography against magnetic resonance
      imaging (MRI) in small animals. METHODS AND RESULTS: We compared circumferential
      strain (CS) and radial strain (RS) measured with echocardiography (velocity
      vector imaging [VVI]) to displacement encoding with stimulated-echo MRI in 2
      mouse models of cardiomyopathy. In 3-month-old mice with gene targeted deficiency
      of cardiac myosin-binding protein-C (cMyBP-C(-/-), n=6) or muscle LIM protein
      (MLP(-/-), n=6), and wild-type mice (n=8), myocardial strains were measured at 3
      cross-sectional levels and averaged to obtain global strains. There was modest
      correlation between VVI and MRI measured strains, with global CS yielding
      stronger correlation compared with global RS (CS R(2)=0.4452 versus RS
      R(2)=0.2794, both P<0.05). Overall, strain measured by VVI was more variable than
      MRI (P<0.05) and the limits of agreement were slightly, but not significantly
      (P=0.14), closer for global CS than RS. Both VVI and MRI strain measurements
      showed significantly lower global CS strain in the knockout groups compared with
      the wild type. The VVI (but not MRI) CS strain measurements were different
      between the 2 knockout groups (-14.5+/-3.8% versus -6.6+/-4.0%, cMyBP-C(-/-)
      versus MLP(-/-) respectively, P<0.05). CONCLUSIONS: Measurements of left
      ventricular CS and RS are feasible in small animals using 2-dimensional
      echocardiography. VVI and MRI strain measurements correlated modestly and the
      agreement between the modalities tended to be greater for CS than RS. Although
      VVI and MRI strains were able to differentiate between wild-type and knockout
      mice, only global CS VVI differentiated between the 2 models of cardiomyopathy.

PMID- 22977128
TI  - CQC says it is improving despite massive failings in the past.

PMID- 22977130
TI  - Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study.
AB  - BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains
      other fat-soluble components such as vitamin A. Before 1999, the cod liver oil
      formula in Norway contained a high concentration of vitamin A (1000 ug per 5 ml).
      High vitamin A status is associated with increased risks of several chronic
      diseases. OBJECTIVE: To investigate the association between cod liver oil intake
      and asthma development. METHODS: In the Nord-Trondelag Health Study, a total of
      25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006
      2008. Current analysis based on 17 528 subjects who were free of asthma and had
      complete information on cod liver oil intake at baseline. Cod liver oil intake
      was defined as daily intake >= 1 month during the year prior to baseline.
      Incident asthma was reported as new-onset asthma during the 11-year follow-up.
      RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for >=
      1 month over the past year. Cod liver oil intake was significantly associated
      with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment
      for age, sex, daily smoking, physical activity, education, socio-economic status,
      family history of asthma, and body mass index (BMI). The positive association was
      consistent across age (< 40/>= 40 years), sex (men/women), family history of
      asthma (yes/no) and BMI subgroups (< 25/>= 25 kg/m(2)). CONCLUSIONS: Intake of
      cod liver oil with high vitamin A content was significantly associated with
      increased incidence of adult-onset asthma.

PMID- 22977131
TI  - A case of cough and breathlessness.

PMID- 22977129
TI  - Association of mild to moderate chronic kidney disease with venous
      thromboembolism: pooled analysis of five prospective general population cohorts.
AB  - BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be
      associated with an increased risk of venous thromboembolism (VTE). Given the high
      prevalence of mild-to-moderate CKD in the general population, in depth analysis
      of this association is warranted. METHODS AND RESULTS: We pooled individual
      participant data from 5 community-based cohorts from Europe (second Nord
      Trondelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage
      Disease [PREVEND], and the Tromso study) and the United States (Atherosclerosis
      Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the
      association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD
      with objectively verified VTE. To estimate adjusted hazard ratios for VTE,
      categorical and continuous spline models were fit by using Cox regression with
      shared-frailty or random-effect meta-analysis. A total of 1178 VTE events
      occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per
      1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59)
      for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95
      (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to
      creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04
      1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09)
      for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR
      and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min
      per 1.73 m(2) or albuminuria >=30 mg/g, (versus no CKD) was 1.54 (95% confidence
      interval, 1.15-2.06). Associations were consistent in subgroups according to age,
      sex, and comorbidities, and for unprovoked versus provoked VTE, as well.
      CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk
      of VTE in the general population, even across the normal eGFR and ACR ranges.

PMID- 22977133
TI  - Association between local neuroretinal function and control of adolescent type 1
      diabetes.
AB  - PURPOSE: To evaluate associations between neuroretinal function measured with
      multifocal electroretinogram (mfERG) and disease variables in adolescents with
      type 1 diabetes and no retinopathy. METHODS: Fundus photographs, blood glucose
      (BG) concentration, HbA1c, and monocular mfERG were performed on 115 adolescent
      patients (mean age +/- SD; 15.7 +/- 1.8 years) and 30 controls (18.0 +/- 2.8
      years). All subjects had best-corrected visual acuity >= 20/20. The 45 degrees 
      mfERG stimulus included 103 hexagons, reversing between dark and bright according
      to a pseudorandom m-sequence. Amplitudes (AMPs) and implicit times (ITs) were
      derived from local mfERG response waveforms, and Z-scores were calculated.
      Retinal maps of abnormality frequencies were generated. Differences between
      controls and patients were evaluated using t-tests. Associations between mfERG
      and age, duration, and diabetes control were examined using linear regression
      analysis. RESULTS: Mean mfERG IT was significantly longer in the patients
      compared with that in the controls (P = 0.019), but AMP was not different (P >
      0.05). In all, 26 eyes (23%) of the patients had abnormal IT and 3 eyes (3%) had
      abnormal AMP. IT abnormalities were essentially distributed randomly across the
      retina. There were too few AMP abnormalities to examine their retinal
      distribution. IT was positively correlated with HbA1c (P < 0.0002) but not
      correlated with diabetes duration, BG, or age. CONCLUSIONS: Higher long-term
      blood glucose concentration is associated with degraded neuroretinal function in
      adolescents with type 1 diabetes and no retinopathy. Over 20% of these patients
      have abnormal neuroretinal function. It will be important to determine
      longitudinally whether the relationship between mfERG IT and diabetes control
      exists within individual adolescent patients.

PMID- 22977134
TI  - Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene
      and its association with CFH and LOC387715 gene polymorphisms in age-related
      macular degeneration.
AB  - PURPOSE: We investigated the association of single nucleotide polymorphism (SNP)
      in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715
      SNPs, with age-related macular degeneration (AMD). METHODS: We enrolled 1388 AMD
      patients with neovascular AMD or geographic atrophy and 487 unrelated control
      subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924),
      and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product
      of CYP46A1, was quantified by gas chromatography-mass spectrometry using an
      authentic deuterated internal standard in subgroups of patients and controls. The
      chi(2) test was used to compare categoric allelic and genotype distributions
      between cases and controls. The odds ratio (OR) with a 95% confidence interval
      (95% CI) was calculated for AMD risk, and adjusted for age and gender.
      Significance levels were set at P < 0.05. RESULTS: The rs754203 SNP in the
      CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P =
      0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001)
      according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0
      (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in
      the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1
      4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene,
      and carrying no risk alleles in the CFH and LOC387715 genes. CONCLUSIONS: The
      rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD
      in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional
      studies with larger sample sizes are needed in AMD subjects at no risk in CFH and
      LOC387715.

PMID- 22977132
TI  - Time outdoors, visual activity, and myopia progression in juvenile-onset myopes.
AB  - PURPOSE: To investigate the association between myopia progression and time spent
      outdoors and in various visual activities. METHODS: Subjects were 835 myopes
      (both principal meridians -0.75 diopters [D] or more myopia by cycloplegic
      autorefraction) in the Collaborative Longitudinal Evaluation of Ethnicity and
      Refractive Error (CLEERE) Study with both progression data and at least one
      measure of activity associated with a progression interval. Activity data were
      collected by parental survey. Average activity level (mean of the activity at the
      beginning and the end of a 1-year progression interval) was the primary predictor
      in a repeated-measures mixed model. The model controlled for age, sex, ethnicity,
      refractive error at the beginning of the progression interval, clinic site, and
      type of autorefractor used. Effects were scaled based on performing an additional
      10 hours per week of an activity. RESULTS: In the multivariate model, the number
      of hours of reading for pleasure per week was not significantly associated with
      annual myopia progression at an a priori level of P <= 0.01, nor were the other
      near activities, the near-work composite variable diopter-hours, or
      outdoor/sports activity. The magnitude of effects was clinically small. For
      example, the largest multivariate effect was that each additional 10 hours of
      reading for pleasure per week at the end of a progression interval was associated
      with an increase in average annual progression by -0.08 D. CONCLUSIONS: Despite
      protective associations previously reported for time outdoors reducing the risk
      of myopia onset, outdoor/sports activity was not associated with less myopia
      progression following onset. Near work also had little meaningful effect on the
      rate of myopia progression.

PMID- 22977136
TI  - A novel method to detect local ganglion cell loss in early glaucoma using
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To test the glaucoma-discriminating ability of a new method for
      detecting local ganglion cell loss using spectral-domain optical coherence
      tomography (OCT). METHODS: This study included 58 glaucomatous and 48 healthy
      eyes from Japanese subjects. Combined thickness of the ganglion cell layer and
      inner plexus layer (GCIPL) was measured on a macular cube scan in Cirrus HD-OCT.
      Average GCIPL thickness within a macular elliptical annulus and minimum GCIPL
      thickness on 360 spokes extending from the inner to the outer radius of the
      elliptical annulus were calculated. Area under the receiver operating
      characteristic curve (AROC) to discriminate between healthy eyes and early (mean
      deviation [MD], >=-6 dB)/advanced (MD, <-6 dB) glaucomatous were compared between
      parameters. RESULTS: Forty-three were normal-tension glaucoma, and 15 were high
      tension glaucoma. The mean minimum GCIPL thickness was 77.0 MUm in healthy eyes
      and 60.6 MUm in glaucomatous eyes (P < 0.001). For the intersession
      repeatability, the coefficients of variation for average GCIPL and minimum GCIPL
      were 0.98 and 1.85 in glaucomatous eyes, and 0.89 and 1.85 in healthy eyes,
      respectively. Minimum GCIPL thickness AROC (0.896) was significantly higher (P =
      0.0062) than average GCIPL thickness (0.821) for early glaucoma, whereas minimum
      GCIPL AROC (0.991) was comparable (P = 0.103) to average GCIPL (0.964) for
      advanced glaucoma. The minimum GCIPL thickness AROC was comparable (P = 0.861) to
      average circumpapillary retinal nerve fiber layer (cpRNFL) thickness (0.890) for
      early glaucoma. CONCLUSIONS: In Japanese patients with 74.1% of normal-tension
      glaucoma, the minimum GCIPL on spokes may be useful for detecting early glaucoma.

PMID- 22977135
TI  - High throughput mass spectrometry-based mutation profiling of primary uveal
      melanoma.
AB  - PURPOSE: We assessed for mutations in a large number of oncogenes and tumor
      suppressor genes in primary uveal melanomas using a high-throughput profiling
      system. METHODS: DNA was extracted and purified from 134 tissue samples from
      fresh-frozen tissues (n = 87) or formalin-fixed, paraffin-embedded tissues (n =
      47) from 124 large uveal melanomas that underwent primary treatment by
      enucleation. DNA was subjected to whole genome amplification and MALDI-TOF mass
      spectrometry-based mutation profiling (>1000 mutations tested across 120
      oncogenes and tumor suppressor genes) using the OncoMap3 platform. All candidate
      mutations, as well as commonly occurring mutations in GNAQ and GNA11, were
      validated using homogeneous mass extension (hME) technology. RESULTS: Of 123
      samples, 97 (79%, representing 89 unique tumors) were amplified successfully,
      passed all quality control steps, and were assayed with the OncoMap platform. A
      total of 58 mutation calls was made for 49 different mutations across 26
      different genes in 34/98 (35%) samples. Of 91 tumors that underwent hME
      validation, 83 (91%) harbored mutations in the GNAQ (47%) or GNA11 (44%) genes,
      while hME validation revealed two tumors with mutations in EGFR. These additional
      mutations occurred in tumors that also had mutations in GNAQ or GNA11.
      CONCLUSIONS: The vast majority of primary large uveal melanomas harbor mutually
      exclusive mutations in GNAQ or GNA11, but very rarely have the oncogenic
      mutations that are reported commonly in other cancers. When present, these other
      mutations were found in conjunction with GNAQ/GNA11 mutations, suggesting that
      these other mutations likely are not the primary drivers of oncogenesis in uveal
      melanoma.

PMID- 22977137
TI  - Neuroretinal cell death in a murine model of closed globe injury: pathological
      and functional characterization.
AB  - PURPOSE: Blunt ocular trauma causes severe retinal injury with death of
      neuroretinal tissue, scarring, and permanent visual loss. The mechanisms of cell
      death are not known, and there are no therapeutic interventions that improve
      visual outcome. We aimed to study the extent, distribution, and functional
      consequences of cell death by developing and characterizing a rat model of
      retinal injury caused by blunt ocular trauma. METHODS: The eyes of anesthetized
      adult rats were injured by either weight drop or low-velocity ballistic trauma
      and assessed by clinical examination, electroretinography, light microscopy,
      electron microscopy, and TUNEL. Projectile velocity was measured and
      standardized. RESULTS: Weight drop did not cause reproducible retinal injury, and
      the energy threshold for retinal injury was similar to that for rupture. Low
      velocity ballistic trauma to the inferior sclera created a reproducible retinal
      injury, with central sclopetaria retinae, retinal necrosis, and surrounding
      commotio retinae with specific photoreceptor cell death and sparing of cells in
      the other retinal layers. The extent of photoreceptor cell death declined and
      necrosis progressed to apoptosis with increasing distance from the impact site.
      CONCLUSIONS: This is the only murine model of closed globe injury and the only
      model of retinal trauma with specific photoreceptor cell death. The clinical
      appearance mirrors that in severe retinal injury after blunt ocular trauma in
      humans, and the ultrastructural features are consistent with human and animal
      studies of commotio retinae. After ocular trauma, photoreceptor apoptosis may be
      prevented and visual outcomes improved by blocking of the cell death pathways.

PMID- 22977138
TI  - Antiangiogenic shift in vitreous after vitrectomy in patients with proliferative
      diabetic retinopathy.
AB  - PURPOSE: We determined whether the concentrations of VEGF, erythropoietin, and
      endostatin in the vitreous are altered after vitrectomy in patient with
      proliferative diabetic retinopathy (PDR). METHODS: We measured the levels of
      VEGF, erythropoietin, and endostatin by sandwich ELISA in vitreous samples
      collected from 38 eyes of 33 patients with PDR before pars plana vitrectomy
      (without IOL implantation) and the same 38 eyes during IOL implantation 3.1 to
      25.7 (mean 6.7) months after the initial vitrectomy. RESULTS: The mean vitreous
      levels of VEGF (964.5 pg/mL) and erythropoietin (1359.5 pg/mL) in the samples
      collected before vitrectomy were significantly higher in patients with PDR than
      in the control patients (0.68 and 70.7 pg/mL, respectively; P < 0.01). The levels
      of VEGF (292.5 pg/mL) and erythropoietin (557.9 pg/mL) in the samples from eyes
      with PDR collected at the time of IOL implantation were significantly lower than
      those collected before vitrectomy (P < 0.01). In contrast, the changes in the
      level of endostatin were not significant after vitrectomy. The VEGF and
      erythropoietin levels in the vitreous fluid from patients with PDR were
      correlated inversely with the interval between the initial vitrectomy and the
      time of the IOL implantation. CONCLUSIONS: The significant decrease in the
      intravitreal concentration of VEGF and erythropoietin, and an absence of a
      significant change in the endostatin indicated a shift in the antiangiogenic
      balance in the vitreous of patients with PDR after successful vitrectomy.

PMID- 22977140
TI  - EphA2 targeted doxorubicin stealth liposomes as a therapy system for choroidal
      neovascularization in rats.
AB  - PURPOSE: To enhance drug uptake in RPE cells, improve efficacy for choroidal
      neovascularization (CNV), and reduce drug toxicity, an EphA2-targeted nanocarrier
      loaded with doxorubicin (DOX) was developed by conjugation with a homing peptide
      YSA. METHODS: The YSA was coupled to PEGylated lipid. Then, YSA-modified DOX
      stealth liposomes (YSA-SSL-DOX) were prepared and characterized. Their uptake in
      a human RPE cell line (ARPE-19) was evaluated. After intravitreous injection,
      their efficacy against CNV was assessed in a laser-induced rat model. Finally,
      TUNEL test and morphology observation on rat retina were conducted. RESULTS: The
      prepared YSA-SSL-DOX was approximately 110 nm in particle size, with an
      encapsulation efficiency of DOX more than 95%. The leakage of DOX from YSA-SSL
      DOX was very slow. The expression of EphA2 on the CNV was confirmed. Both flow
      cytometry and confocal microscopy studies revealed that YSA-SSL-DOX could
      facilitate the uptake of liposomal DOX into ARPE-19 cells. Treatment with YSA-SSL
      DOX (2.5 MUg DOX) resulted in a significant reduction in the CNV area of rats
      compared with the unmodified liposomal DOX and normal saline (P < 0.05). No
      obvious toxicity of YSA-SSL-DOX on rat retina was found. CONCLUSIONS: EphA2
      targeted stealth liposomes might be an effective delivery and therapy system for
      angiogenesis-related diseases in the retina.

PMID- 22977139
TI  - Extraocular muscle afferent signals modulate visual attention.
AB  - PURPOSE: Extraocular muscle afferent signals contribute to oculomotor control and
      visual localization. Prompted by the close links between the oculomotor and
      attention systems, it was investigated whether these proprioceptive signals also
      modulated the allocation of attention in space. METHODS: A suction sclera contact
      lens was used to impose an eye rotation on the nonviewing, dominant eye. With
      their viewing, nondominant eye, participants (n = 4) fixated centrally and
      detected targets presented at 5 degrees  in the left or right visual hemifield.
      The position of the viewing eye was monitored throughout the experiment. As a
      control, visual localization was tested using finger pointing without visual
      feedback of the hand, whereas the nonviewing eye remained deviated. RESULTS: The
      sustained passive rotation of the occluded, dominant eye, while the other eye
      maintained central fixation, resulted in a lateralized change in the
      detectability of visual targets. In all participants, the advantage in speed and
      accuracy for detecting right versus left hemifield targets that occurred during a
      sustained rightward eye rotation of the dominant eye was reduced or reversed by a
      leftward eye rotation. The control experiment confirmed that the eye deviation
      procedure caused pointing errors consistent with an approximately 2 degrees 
      shift in perceived eye position, in the direction of rotation of the nonviewing
      eye. CONCLUSIONS: With the caveat of the small number of participants, these
      results suggest that extraocular muscle afferent signals modulate the deployment
      of attention in visual space.

PMID- 22977141
TI  - When is a further clinical trial justified?

PMID- 22977142
TI  - Taught a lesson by taut skin.

PMID- 22977143
TI  - Fighting neglected tropical diseases in the southern United States.

PMID- 22977144
TI  - Charity challenges closure of children's heart surgery unit at Leeds.

PMID- 22977145
TI  - Separating spatial search and efficiency rates as components of predation risk.
AB  - Predation risk is an important driver of ecosystems, and local spatial variation
      in risk can have population-level consequences by affecting multiple components
      of the predation process. I use resource selection and proportional hazard time
      to-event modelling to assess the spatial drivers of two key components of risk-
      the search rate (i.e. aggregative response) and predation efficiency rate (i.e.
      functional response)--imposed by wolves (Canis lupus) in a multi-prey system. In
      my study area, both components of risk increased according to topographic
      variation, but anthropogenic features affected only the search rate. Predicted
      models of the cumulative hazard, or risk of a kill, underlying wolf search paths
      validated well with broad-scale variation in kill rates, suggesting that spatial
      hazard models provide a means of scaling up from local heterogeneity in predation
      risk to population-level dynamics in predator-prey systems. Additionally, I
      estimated an integrated model of relative spatial predation risk as the product
      of the search and efficiency rates, combining the distinct contributions of
      spatial heterogeneity to each component of risk.

PMID- 22977146
TI  - Modelling the coevolution of joint attention and language.
AB  - Joint attention (JA) is important to many social, communicative activities,
      including language, and humans exhibit a considerably high level of JA compared
      with non-human primates. We propose a coevolutionary hypothesis to explain this
      degree-difference in JA: once JA started to aid linguistic comprehension, along
      with language evolution, communicative success (CS) during cultural transmission
      could enhance the levels of JA among language users. We illustrate this
      hypothesis via a multi-agent computational model, where JA boils down to a
      genetically transmitted ability to obtain non-linguistic cues aiding
      comprehension. The simulation results and statistical analysis show that: (i) the
      level of JA is correlated with the understandability of the emergent language;
      and (ii) CS can boost an initially low level of JA and 'ratchet' it up to a
      stable high level. This coevolutionary perspective helps explain the degree
      difference in many language-related competences between humans and non-human
      primates, and reflects the importance of biological evolution, individual
      learning and cultural transmission to language evolution.

PMID- 22977147
TI  - An inclusive fitness analysis of synergistic interactions in structured
      populations.
AB  - We study the evolution of a pair of competing behavioural alleles in a structured
      population when there are non-additive or 'synergistic' fitness effects. Under a
      form of weak selection and with a simple symmetry condition between a pair of
      competing alleles, Tarnita et al. provide a surprisingly simple condition for one
      allele to dominate the other. Their condition can be obtained from an analysis of
      a corresponding simpler model in which fitness effects are additive. Their result
      uses an average measure of selective advantage where the average is taken over
      the long-term--that is, over all possible allele frequencies--and this precludes
      consideration of any frequency dependence the allelic fitness might exhibit.
      However, in a considerable body of work with non-additive fitness effects--for
      example, hawk-dove and prisoner's dilemma games--frequency dependence plays an
      essential role in the establishment of conditions for a stable allele-frequency
      equilibrium. Here, we present a frequency-dependent generalization of their
      result that provides an expression for allelic fitness at any given allele
      frequency p. We use an inclusive fitness approach and provide two examples for an
      infinite structured population. We illustrate our results with an analysis of the
      hawk-dove game.

PMID- 22977148
TI  - Positive selection at the ASPM gene coincides with brain size enlargements in
      cetaceans.
AB  - The enlargement of cetacean brain size represents an enigmatic event in mammalian
      evolution, yet its genetic basis remains poorly explored. One candidate gene
      associated with brain size evolution is the abnormal spindle-like microcephaly
      associated (ASPM), as mutations in this gene cause severe reductions in the
      cortical size of humans. Here, we investigated the ASPM gene in representative
      cetacean lineages and previously published sequences from other mammals to test
      whether the expansion of the cetacean brain matched adaptive ASPM evolution
      patterns. Our analyses yielded significant evidence of positive selection on the
      ASPM gene during cetacean evolution, especially for the Odontoceti and
      Delphinoidea lineages. These molecular patterns were associated with two major
      events of relative brain size enlargement in odontocetes and delphinoids. It is
      of particular interest to find that positive selection was restricted to
      cetaceans and primates, two distant lineages both characterized by a massive
      expansion of brain size. This result is suggestive of convergent molecular
      evolution, although no site-specific convergence at the amino acid level was
      found.

PMID- 22977149
TI  - Mutualism and evolutionary multiplayer games: revisiting the Red King.
AB  - Coevolution of two species is typically thought to favour the evolution of faster
      evolutionary rates helping a species keep ahead in the Red Queen race, where 'it
      takes all the running you can do to stay where you are'. In contrast, if species
      are in a mutualistic relationship, it was proposed that the Red King effect may
      act, where it can be beneficial to evolve slower than the mutualistic species.
      The Red King hypothesis proposes that the species which evolves slower can gain a
      larger share of the benefits. However, the interactions between the two species
      may involve multiple individuals. To analyse such a situation, we resort to
      evolutionary multiplayer games. Even in situations where evolving slower is
      beneficial in a two-player setting, faster evolution may be favoured in a
      multiplayer setting. The underlying features of multiplayer games can be crucial
      for the distribution of benefits. They also suggest a link between the evolution
      of the rate of evolution and group size.

PMID- 22977150
TI  - Multiple nuclear genes and retroposons support vicariance and dispersal of the
      palaeognaths, and an Early Cretaceous origin of modern birds.
AB  - The origin and timing of the diversification of modern birds remains
      controversial, primarily because phylogenetic relationships are incompletely
      resolved and uncertainty persists in molecular estimates of lineage ages. Here,
      we present a species tree for the major palaeognath lineages using 27 nuclear
      genes and 27 archaic retroposon insertions. We show that rheas are sister to the
      kiwis, emu and cassowaries, and confirm ratite paraphyly because tinamous are
      sister to moas. Divergence dating using 10 genes with broader taxon sampling,
      including emu, cassowary, ostrich, five kiwis, two rheas, three tinamous, three
      extinct moas and 15 neognath lineages, suggests that three vicariant events and
      possibly two dispersals are required to explain their historical biogeography.
      The age of crown group birds was estimated at 131 Ma (95% highest posterior
      density 122-138 Ma), similar to previous molecular estimates. Problems associated
      with gene tree discordance and incomplete lineage sorting in birds will require
      much larger gene sets to increase species tree accuracy and improve error in
      divergence times. The relatively rapid branching within neoaves pre-dates the
      extinction of dinosaurs, suggesting that the genesis of the radiation within this
      diverse clade of birds was not in response to the Cretaceous-Paleogene extinction
      event.

PMID- 22977151
TI  - Mating system affects population performance and extinction risk under
      environmental challenge.
AB  - Failure of organisms to adapt to sudden environmental changes may lead to
      extinction. The type of mating system, by affecting fertility and the strength of
      sexual selection, may have a major impact on a population's chances to adapt and
      survive. Here, we use experimental evolution in bulb mites (Rhizoglyphus robini)
      to examine the effects of the mating system on population performance under
      environmental change. We demonstrate that populations in which monogamy was
      enforced suffered a dramatic fitness decline when evolving at an increased
      temperature, whereas the negative effects of change in a thermal environment were
      alleviated in polygamous populations. Strikingly, within 17 generations, all
      monogamous populations experiencing higher temperature went extinct, whereas all
      polygamous populations survived. Our results show that the mating system may have
      dramatic effects on the risk of extinction under environmental change.

PMID- 22977153
TI  - Response of an arctic predator guild to collapsing lemming cycles.
AB  - Alpine and arctic lemming populations appear to be highly sensitive to climate
      change, and when faced with warmer and shorter winters, their well-known high
      amplitude population cycles may collapse. Being keystone species in tundra
      ecosystems, changed lemming dynamics may convey significant knock-on effects on
      trophically linked species. Here, we analyse long-term (1988-2010), community
      wide monitoring data from two sites in high-arctic Greenland and document how a
      collapse in collared lemming cyclicity affects the population dynamics of the
      predator guild. Dramatic changes were observed in two highly specialized lemming
      predators: snowy owl and stoat. Following the lemming cycle collapse, snowy owl
      fledgling production declined by 98 per cent, and there was indication of a
      severe population decline of stoats at one site. The less specialized long-tailed
      skua and the generalist arctic fox were more loosely coupled to the lemming
      dynamics. Still, the lemming collapse had noticeable effects on their
      reproductive performance. Predator responses differed somewhat between sites in
      all species and could arise from site-specific differences in lemming dynamics,
      intra-guild interactions or subsidies from other resources. Nevertheless,
      population extinctions and community restructuring of this arctic endemic
      predator guild are likely if the lemming dynamics are maintained at the current
      non-cyclic, low-density state.

PMID- 22977152
TI  - Gene duplication as a mechanism of genomic adaptation to a changing environment.
AB  - A subject of extensive study in evolutionary theory has been the issue of how
      neutral, redundant copies can be maintained in the genome for long periods of
      time. Concurrently, examples of adaptive gene duplications to various
      environmental conditions in different species have been described. At this point,
      it is too early to tell whether or not a substantial fraction of gene copies have
      initially achieved fixation by positive selection for increased dosage.
      Nevertheless, enough examples have accumulated in the literature that such a
      possibility should be considered. Here, I review the recent examples of adaptive
      gene duplications and make an attempt to draw generalizations on what types of
      genes may be particularly prone to be selected for under certain environmental
      conditions. The identification of copy-number variation in ecological field
      studies of species adapting to stressful or novel environmental conditions may
      improve our understanding of gene duplications as a mechanism of adaptation and
      its relevance to the long-term persistence of gene duplications.

PMID- 22977154
TI  - The epidemiological consequences of immune priming.
AB  - Exposure to low doses of pathogens that do not result in the host becoming
      infectious may 'prime' the immune response and increase protection to subsequent
      challenge. There is increasing evidence that such immune priming is a widespread
      and important feature of invertebrate host-pathogen interactions. Immune priming
      clearly has implications for individual hosts but will also have population-level
      implications. We present a susceptible-primed-infectious model-in contrast to the
      classic susceptible-infectious-recovered framework-to investigate the impacts of
      immune priming on pathogen persistence and population stability. We describe
      impacts of immune priming on the epidemiology of the disease in both constant and
      seasonal environments. A key result is that immune priming may act to destabilize
      population dynamics. In particular, when the proportion of individuals becoming
      primed rather than infected is high, but this priming does not confer full
      immunity, the population may be strongly destabilized through the generation of
      limit cycles. We discuss the implications of our model both in the context of
      invertebrate immunity and more widely.

PMID- 22977155
TI  - The impact of past climate change on genetic variation and population
      connectivity in the Icelandic arctic fox.
AB  - Previous studies have suggested that the presence of sea ice is an important
      factor in facilitating migration and determining the degree of genetic isolation
      among contemporary arctic fox populations. Because the extent of sea ice is
      dependent upon global temperatures, periods of significant cooling would have had
      a major impact on fox population connectivity and genetic variation. We tested
      this hypothesis by extracting and sequencing mitochondrial control region
      sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth
      century AD archaeological sites in northeast Iceland, both of which predate the
      Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that
      five haplotypes have been observed in modern Icelandic foxes, a single haplotype
      was shared among all of the ancient individuals. Results from simulations within
      an approximate Bayesian computation framework suggest that the rapid increase in
      Icelandic arctic fox haplotype diversity can only be explained by sea-ice
      mediated fox immigration facilitated by the Little Ice Age.

PMID- 22977156
TI  - Sex peptide of Drosophila melanogaster males is a global regulator of
      reproductive processes in females.
AB  - Seminal fluid proteins (Sfps) alter female behaviour and physiology and can
      mediate sexual conflict. In Drosophila melanogaster, a single Sfp, the sex
      peptide (SP), triggers remarkable post-mating responses in females, including
      altered fecundity, feeding, immunity and sexual receptivity. These effects can
      favour the evolutionary interests of males while generating costs in females. We
      tested the hypothesis that SP is an upstream master-regulator able to induce
      diverse phenotypes through efficient induction of widespread transcriptional
      changes in females. We profiled mRNA responses to SP in adult female abdomen
      (Abd) and head+thorax (HT) tissues using microarrays at 3 and 6 h following
      mating. SP elicited a rich, subtle signature of temporally and spatially
      controlled mRNAs. There were significant alterations to genes linked to egg
      development, early embryogenesis, immunity, nutrient sensing, behaviour and,
      unexpectedly, phototransduction. There was substantially more variation in the
      direction of differential expression across time points in the HT versus Abd. The
      results support the idea that SP is an important regulator of gene expression in
      females. The expression of many genes in one sex can therefore be under the
      influence of a regulator expressed in the other. This could influence the extent
      of sexual conflict both within and between loci.

PMID- 22977157
TI  - How hierarchical is language use?
AB  - It is generally assumed that hierarchical phrase structure plays a central role
      in human language. However, considerations of simplicity and evolutionary
      continuity suggest that hierarchical structure should not be invoked too hastily.
      Indeed, recent neurophysiological, behavioural and computational studies show
      that sequential sentence structure has considerable explanatory power and that
      hierarchical processing is often not involved. In this paper, we review evidence
      from the recent literature supporting the hypothesis that sequential structure
      may be fundamental to the comprehension, production and acquisition of human
      language. Moreover, we provide a preliminary sketch outlining a non-hierarchical
      model of language use and discuss its implications and testable predictions. If
      linguistic phenomena can be explained by sequential rather than hierarchical
      structure, this will have considerable impact in a wide range of fields, such as
      linguistics, ethology, cognitive neuroscience, psychology and computer science.

PMID- 22977158
TI  - Influence of acquired beta-lactamases on the evolution of spontaneous carbapenem
      resistance in Escherichia coli.
AB  - OBJECTIVES: To investigate the influence of plasmid-borne beta-lactamases on the
      evolution of spontaneous carbapenem resistance in Escherichia coli and the
      fitness costs associated with resistance. METHODS: Stepwise selection of
      carbapenem-resistant mutants with or without the extended-spectrum beta-lactamase
      (ESBL)-encoding plasmid pUUH239.2 was performed. Mutation rates and mutational
      pathways to resistance were determined. In vitro-selected and constructed mutants
      were characterized regarding the MICs of the carbapenems, porin expression
      profiles, growth rates and the presence of mutations in the porins ompC/ompF and
      their regulatory genes. The influence of the plasmid-encoded beta-lactamases TEM
      1, OXA-1 and CTX-M-15 on resistance development was determined. RESULTS: Results
      show that E. coli readily developed reduced carbapenem susceptibility and
      clinical resistance levels by a combination of porin loss and increased beta
      lactamase expression, especially towards ertapenem. All tested beta-lactamases
      (CTX-M-15, TEM-1 and OXA-1) contributed to reduced carbapenem susceptibility in
      the absence of porin expression. However, complete loss of porin expression
      conferred a 20% fitness cost on the bacterial growth rate. Increased beta
      lactamase expression through spontaneous gene amplification on the plasmid was a
      major resistance factor. CONCLUSIONS: Plasmid-encoded beta-lactamases, including
      non-ESBL enzymes, have a strong influence on the frequency and resistance level
      of spontaneous carbapenem-resistant mutants. The fitness cost associated with the
      loss of OmpC/OmpF in E. coli most likely reduces the survivability of porin
      mutants and could explain why they have not emerged as a clinical problem in this
      species.

PMID- 22977159
TI  - Comment on: Are susceptibility tests enough, or should laboratories still seek
      ESBLs and carbapenemases directly?

PMID- 22977161
TI  - Group advises what specialised services should be commissioned nationally.

PMID- 22977160
TI  - Mutations selected in HIV-2-infected patients failing a regimen including
      atazanavir.
AB  - OBJECTIVES: To investigate mutations selected in viruses from HIV-2-infected
      patients failing a highly active antiretroviral treatment (HAART) regimen
      including atazanavir/ritonavir. METHODS: Twenty-eight HIV-2-infected patients
      previously exposed to atazanavir/ritonavir and failing therapy were studied. The
      protease (PR) gene was amplified and sequenced, and mutations emerging under
      atazanavir/ritonavir selective pressure were reported. RESULTS: The I50L mutation
      emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including
      atazanavir/ritonavir. Besides I50L, four PR mutations previously associated with
      protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of
      unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also
      identified in this small group of patients. CONCLUSIONS: Several mutations were
      associated with virological failure of a regimen including atazanavir/ritonavir
      in HIV-2-infected patients, including I50L for the first time. It should be
      included in HIV-2 algorithms for interpretation of genotypic resistance data, and
      taken into account when making therapeutic decisions for HIV-2-infected patients.

PMID- 22977162
TI  - HIV positive man starts legal action in Zimbabwe to ensure prisoners receive
      right drugs.

PMID- 22977163
TI  - Routine screening for ovarian cancer harms more than it helps, says US authority.

PMID- 22977164
TI  - Persistent health disparities in the US signal need for new thinking.

PMID- 22977165
TI  - Nephrogenic systemic fibrosis-like effects of magnetic resonance imaging contrast
      agents in rats with adenine-induced renal failure.
AB  - Nephrogenic systemic fibrosis (NSF) is a scleroderma-like disease associated with
      prior administration of certain gadolinium chelates (GCs). NSF occurs in patients
      with severe renal failure. The purpose of this study was to set up a rat model of
      GC-associated NSF to elucidate the mechanism of this devastating disease.
      Firstly, after characterization of the model, male Wistar rats received a 0.75%
      adenine-enriched diet for 8, 14, or 16 days to obtain various degrees of renal
      failure. Rats received five consecutive daily iv injections of saline or
      gadodiamide (2.5 mmol/kg/day). Secondly, the safety profile and in vivo
      propensity to dissociate of all categories of marketed GCs (gadoterate,
      gadobutrol, gadobenate, gadopentetate, and gadodiamide) were compared in rats
      receiving adenine-enriched diet for 16 days. Serial skin biopsies were performed
      for blinded histopathological study. Total Gd concentration in tissues was
      measured by Inductively Coupled Plasma Mass Spectrometry. Relaxometry was used to
      evaluate the presence of dissociated Gd in skin and bone. Gadodiamide-induced
      high mortality and skin lesions (dermal fibrosis, calcification, and
      inflammation) were related to adenine diet duration. No skin lesions were
      observed with other molecules. Unlike macrocyclic GCs, gadodiamide,
      gadopentetate, and gadobenate gradually increased the r(1) relaxivity value,
      consistent with in vivo dissociation and release of soluble Gd (or, in the case
      of gadobenate, the consequence of protein binding). Gadodiamide-induced cutaneous
      and systemic toxicity depended on baseline renal function. We demonstrate in vivo
      dissociation of linear GCs, gadodiamide, and gadopentetate, whereas macrocyclic
      agents remained stable over the study period.

PMID- 22977166
TI  - Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine
      phosphorylase in BALB/c mice and beagle dogs: an enzyme-replacement therapy for
      mitochondrial neurogastrointestinal encephalomyopathy.
AB  - Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is currently under
      development as an enzyme replacement therapy for mitochondrial
      neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder
      caused by a deficiency of thymidine phosphorylase. The rationale for the
      development of EE-TP is based on the pathologically elevated metabolites
      (thymidine and deoxyuridine) being able to freely diffuse across the erythrocyte
      membrane where the encapsulated enzyme catalyses their metabolism to the normal
      products. The systemic toxic potential of EE-TP was assessed when administered
      intermittently by iv bolus injection to BALB/c mice and Beagle dogs for 4 weeks.
      The studies consisted of one control group receiving sham-loaded erythrocytes
      twice weekly and two treated groups, one dosed once every 2 weeks and the other
      dosed twice per week. The administration of EE-TP to BALB/c mice resulted in
      thrombi/emboli in the lungs and spleen enlargement. These findings were also seen
      in the control group, and there was no relationship to the number of doses
      administered. In the dog, transient clinical signs were associated with EE-TP
      administration, suggestive of an immune-based reaction. Specific antithymidine
      phosphorylase antibodies were detected in two dogs and in a greater proportion of
      mice treated once every 2 weeks. Nonspecific antibodies were detected in all EE
      TP-treated animals. In conclusion, these studies do not reveal serious toxicities
      that would preclude a clinical trial of EE-TP in patients with MNGIE, but caution
      should be taken for infusion-related reactions that may be related to the
      production of nonspecific antibodies or a cell-based immune response.

PMID- 22977167
TI  - Effects of ozone and particulate matter on cardiac mechanics: role of the atrial
      natriuretic peptide gene.
AB  - A positive association between air pollution exposure and increased human risk of
      chronic heart disease progression is well established. In the current study, we
      test two hypotheses: (1) the cardiac compensatory changes in response to air
      pollution are dependent on its composition and (2) specific cardiac adaptations
      are regulated by atrial natriuretic peptide (ANP). We address these hypotheses by
      initially examining the exposure effects of ozone (O(3)) and/or particulate
      matter (PM) on cardiac function in C57Bl/6J (B6) mice. Subsequently, the results
      are compared with cardiac functional changes to the same exposures in Nppa (the
      precursor gene for ANP) knockout (KO) mice. Separate groups of mice underwent 3
      consecutive days of the same exposure sequence for 3h each consisting of the
      following: (1) 6h of filtered air (FAFA), (2) O(3) then FA (O(3)FA), (3) FA then
      carbon black (FACB), or (4) O(3) then CB. Cardiac function was assessed using a
      conductance catheter to generate cardiac pressure-volume loops 8-10h following
      each exposure sequence. As compared with FAFA, each sequence led to a substantial
      drop (as much as 33%) in stroke volume and cardiac output. However, these losses
      of cardiac function occurred by different compensatory mechanisms dependent on
      the pollutant composition. For example, O(3)FA exposure led to reductions in both
      end-systolic and end-diastolic left ventricular (LV) volumes, whereas FACB
      exposure led an increase in end-diastolic LV volume. These same cardiac
      compensatory changes were largely abolished in Nppa KO mice following O(3)FA or
      FACB exposure. These results suggest that cardiac functional changes in response
      to air pollution exposure are strongly dependent on the pollutant constituents,
      especially related to O(3) and/or PM. Furthermore, ANP regulation appears to be
      crucial to these cardiac compensatory mechanisms induced by air pollution.

PMID- 22977168
TI  - CTNNA3 (alpha-catenin) gene variants are associated with diisocyanate asthma: a
      replication study in a Caucasian worker population.
AB  - Recently, a genome-wide association study (GWAS) conducted in Korean subjects
      identified four CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs)
      (rs10762058, rs7088181, rs1786929, and rs4378283) associated with diisocyanate
      induced occupational asthma (DA). The CTNNA3 gene codes for a cadherin involved
      in formation of stretch-resistant cell-cell adhesions. We conducted a candidate
      gene association study to replicate these findings in Caucasian workers.
      Genotyping was performed on DNA using a 5' nuclease PCR assay collected from 410
      diisocyanate-exposed and predominantly Canadian workers including 132 workers
      with DA confirmed by a specific inhalation challenge (DA+); 131 symptomatic
      workers in whom DA was excluded by a negative challenge (DA-); and 147
      hexamethylene diisocyanate-exposed asymptomatic workers (AWs). As in the Korean
      study, highly linked CTNNA3 rs7088181 and rs10762058 SNPs (but not rs4378283 and
      rs1786929) were significantly associated with DA+ when compared with AWs but not
      in comparison with DA- workers (p <= 0.05). After adjusting for potentially
      confounding variables of age, smoking status, and duration of exposure, minor
      allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA
      compared with AWs (OR = 9.05 [95% CI: 1.69, 48.54] and OR = 6.82 [95% CI: 1.65,
      28.24], respectively). In conclusion, we replicated results from the only
      reported GWAS study of DA demonstrating an association between two closely linked
      CTNNA3 gene SNPs and DA. These findings lend further support to the clinical
      relevance of these genotypes in predicting susceptibility to DA and the potential
      importance of catenins in the disease process.

PMID- 22977170
TI  - The development of structure-activity relationships for mitochondrial
      dysfunction: uncoupling of oxidative phosphorylation.
AB  - Mitochondrial dysfunction has been implicated as an important factor in the
      development of idiosyncratic organ toxicity. An ability to predict mitochondrial
      dysfunction early in the drug development process enables the deselection of
      those drug candidates with potential safety liabilities, allowing resources to be
      focused on those compounds with the highest chance of success to the market. A
      database of greater than 2000 compounds was analyzed to identify structural and
      physicochemical features associated with the uncoupling of oxidative
      phosphorylation (herein defined as an increase in basal respiration). Many
      toxicophores associated with potent uncoupling activity were identified, and
      these could be divided into two main mechanistic classes, protonophores and redox
      cyclers. For the protonophores, potent uncoupling activity was often promoted by
      high lipophilicity and apparent stabilization of the anionic charge resulting
      from deprotonation of the protonophore. The potency of redox cyclers did not
      appear to be prone to variations in lipophilicity. Only 11 toxicophores were of
      sufficient predictive performance that they could be incorporated into a
      structural-alert model. Each alert was associated with one of three confidence
      levels (high, medium, and low) depending upon the lipophilicity-activity profile
      of the structural class. The final model identified over 68% of those compounds
      with potent uncoupling activity and with a value for specificity above 99%. We
      discuss the advantages and limitations of this approach and conclude that
      although structural alert methodology is useful for identifying toxicophores
      associated with mitochondrial dysfunction, they are not a replacement for the
      mitochondrial dysfunction assays in early screening paradigms.

PMID- 22977169
TI  - TCDD-elicited effects on liver, serum, and adipose lipid composition in C57BL/6
      mice.
AB  - The aryl hydrocarbon receptor (AhR) mediates alterations in hepatic lipid
      composition elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to
      further investigate the effects of TCDD, liver, serum, and gonadal white adipose
      tissue (gWAT) fatty acid methyl esters (FAMEs) and lipids were examined in fasted
      4-week-old female mice orally gavaged with 30 ug/kg TCDD at 24, 72, and 168 h
      postdose. Mean hepatic FAME levels increased (236.7 umol/g in controls compared
      with 392.2 umol/g in TCDD treated) with minimal changes in gWAT and serum. In the
      liver, TCDD decreased saturated fatty acids (SFAs 16:0, 18:0, 20:0, and 22:0) and
      increased monounsaturated fatty acids (MUFAs 16:1n7, 18:1n9, and 20:1n9). Hepatic
      polyunsaturated fatty acids (PUFAs) 20:2n6, 20:3n6, 18:3n3, and 22:5n3 also
      increased, whereas 20:4n6 and 22:6n3 levels decreased. gWAT PUFAs 20:2n6 and
      20:3n6 exhibited modest increases, whereas serum 18:0 decreased and 18:1n9
      increased. Serum analyses also identified a ~25% decrease in total cholesterol
      (CHOL), low-density lipoprotein (LDL), and high-density lipoprotein following
      TCDD treatment. The decrease in serum CHOL was consistent with the induction of
      hepatic reverse CHOL transport genes Lcat (2.0-fold), Apoa1 (1.7-fold), and Ldlr
      (3.6-fold), and the repression of CHOL biosynthesis genes Hmgcs1 (-2.1-fold) and
      Hmgcr (-2.3-fold). In addition, TCDD decreased serum Apob100 (4.4-fold) and
      Apob48 (2.2-fold) protein levels, suggesting serum lipid clearance and decreased
      hepatic efflux. Collectively, the TCDD-elicited decreases in serum lipid levels
      are consistent with AhR-mediated enhancement of dietary fat distribution to the
      liver.

PMID- 22977172
TI  - Assessment of entrance surface dose and health risk from common radiology
      examinations in Iran.
AB  - Medical X-ray exposures are the largest man-made source of population exposure to
      ionising radiation in many countries. Although information on medical exposure is
      already incorporated into national legislative documents, in Isfahan there is no
      data on the assessment of patient's entrance surface dose (ESD) and the health
      risk from conventional radiography in daily clinical practice. The aim of this
      study was to investigate ESDs and the consequent health risk for the patients
      undergoing routine X-ray procedures in hospitals  under the control of Isfahan
      University of Medical Sciences, Iran, in year 2011. The values of ESDs were
      measured for common radiographical examinations with the highest absorbed dose to
      the patient in seven hospitals (Alzahra, Ashrafi-Khomeini-shahr, Feyz, Isabne
      Maryam, Kashani, Nour-Aliasghar and Seyed-Al Shohada) and six stationary X-ray
      machines (General Electric, USA; Phillips, The Netherlands; Siemens, Germany;
      Shimadzu, Japan; Toshiba, Japan and Varian, USA). The results of the ESD
      measurements as well as the calculated effective dose values between different X
      ray examinations showed values significantly greater than those recorded in some
      other countries especially for the high tube potential technique (such as the
      skull) by factors of 2.5-5.0. Based on the fatality risk of 5 % per sievert, it
      was estimated that, for chest and skull examinations approximately two (40.18
      person-Sv*5 % per sievert) and one (2.53 person-Sv*5 % per sievert) cases of
      health risk, respectively, may in the future be attributable to diagnostic X rays
      done in year 2011 in Isfahan. Efforts should be taken to further lower patient
      doses while securing image quality. The need to provide relevant education and
      training to staff in the radiology sections is of utmost importance.

PMID- 22977173
TI  - Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint
      activation in response to replication stress.
AB  - DNA damage encountered by DNA replication forks poses risks of genome
      destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause
      cell cycle arrest, promote repair and induce programed cell death when damage is
      severe. Checkpoints are critical parts of the DNA damage response network that
      act to suppress cancer. DNA damage and perturbation of replication machinery
      causes replication stress, characterized by accumulation of single-stranded DNA
      bound by replication protein A (RPA), which triggers activation of ataxia
      telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit
      of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated
      (ATM) and ATR] has well characterized roles in DNA double-strand break repair,
      but poorly understood roles in replication stress-induced RPA phosphorylation. We
      show that DNA-PKcs mutant cells fail to arrest replication following stress, and
      mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the
      proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M
      arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects
      observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA
      PKcs show sustained H2AX phosphorylation in response to replication stress that
      persists in cells entering mitosis, indicating inappropriate mitotic entry with
      unrepaired damage.

PMID- 22977174
TI  - Estrogen-induced upregulation and 3'-UTR shortening of CDC6.
AB  - 3'-Untranslated region (UTR) shortening of mRNAs via alternative polyadenylation
      (APA) has important ramifications for gene expression. By using proximal APA
      sites and switching to shorter 3'-UTRs, proliferating cells avoid miRNA-mediated
      repression. Such APA and 3'-UTR shortening events may explain the basis of some
      of the proto-oncogene activation cases observed in cancer cells. In this study,
      we investigated whether 17 beta-estradiol (E2), a potent proliferation signal,
      induces APA and 3'-UTR shortening to activate proto-oncogenes in estrogen
      receptor positive (ER+) breast cancers. Our initial probe based screen of
      independent expression arrays suggested upregulation and 3'-UTR shortening of an
      essential regulator of DNA replication, CDC6 (cell division cycle 6), upon E2
      treatment. We further confirmed the E2- and ER-dependent upregulation and 3'UTR
      shortening of CDC6, which lead to increased CDC6 protein levels and higher BrdU
      incorporation. Consequently, miRNA binding predictions and dual luciferase assays
      suggested that 3'-UTR shortening of CDC6 was a mechanism to avoid 3'-UTR
      dependent negative regulations. Hence, we demonstrated CDC6 APA induction by the
      proliferative effect of E2 in ER+ cells and provided new insights into the
      complex regulation of APA. E2-induced APA is likely to be an important but
      previously overlooked mechanism of E2-responsive gene expression.

PMID- 22977175
TI  - The structural basis for the interaction between the CAF1 nuclease and the NOT1
      scaffold of the human CCR4-NOT deadenylase complex.
AB  - The CCR4-NOT complex plays a crucial role in post-transcriptional mRNA regulation
      in eukaryotic cells. It catalyzes the removal of mRNA poly(A) tails, thereby
      repressing translation and committing mRNAs to decay. The conserved core of the
      complex consists of a catalytic module comprising two deadenylases (CAF1/POP2 and
      CCR4a/b) and the NOT module, which contains at least NOT1, NOT2 and NOT3. NOT1
      bridges the interaction between the two modules and therefore, acts as a scaffold
      protein for the assembly of the complex. Here, we present the crystal structures
      of the CAF1-binding domain of human NOT1 alone and in complex with CAF1. The NOT1
      domain comprises five helical hairpins that adopt an MIF4G (middle portion of
      eIF4G) fold. This NOT1 MIF4G domain binds CAF1 through a pre-formed interface and
      leaves the CAF1 catalytic site fully accessible to RNA substrates. The
      conservation of critical structural and interface residues suggests that the NOT1
      MIF4G domain adopts a similar fold and interacts with CAF1 in a similar manner in
      all eukaryotes. Our findings shed light on the assembly of the CCR4-NOT complex
      and provide the basis for dissecting the role of the NOT module in mRNA
      deadenylation.

PMID- 22977176
TI  - SLiMPrints: conservation-based discovery of functional motif fingerprints in
      intrinsically disordered protein regions.
AB  - Large portions of higher eukaryotic proteomes are intrinsically disordered, and
      abundant evidence suggests that these unstructured regions of proteins are rich
      in regulatory interaction interfaces. A major class of disordered interaction
      interfaces are the compact and degenerate modules known as short linear motifs
      (SLiMs). As a result of the difficulties associated with the experimental
      identification and validation of SLiMs, our understanding of these modules is
      limited, advocating the use of computational methods to focus experimental
      discovery. This article evaluates the use of evolutionary conservation as a
      discriminatory technique for motif discovery. A statistical framework is
      introduced to assess the significance of relatively conserved residues,
      quantifying the likelihood a residue will have a particular level of conservation
      given the conservation of the surrounding residues. The framework is expanded to
      assess the significance of groupings of conserved residues, a metric that forms
      the basis of SLiMPrints (short linear motif fingerprints), a de novo motif
      discovery tool. SLiMPrints identifies relatively overconstrained proximal
      groupings of residues within intrinsically disordered regions, indicative of
      putatively functional motifs. Finally, the human proteome is analysed to create a
      set of highly conserved putative motif instances, including a novel site on
      translation initiation factor eIF2A that may regulate translation through binding
      of eIF4E.

PMID- 22977177
TI  - Strand directionality affects cation binding and movement within tetramolecular G
      quadruplexes.
AB  - Nuclear magnetic resonance study of G-quadruplex structures formed by d(TG(3)T)
      and its modified analogs containing a 5'-5' or 3'-3' inversion of polarity sites,
      namely d(3'TG5'-5'G(2)T3'), d(3'T5'-5'G(3)T3') and d(5'TG3'-3'G(2)T5')
      demonstrates formation of G-quadruplex structures with tetrameric topology and
      distinct cation-binding preferences. All oligonucleotides are able to form
      quadruplex structures with two binding sites, although the modified
      oligonucleotides also form, in variable amounts, quadruplex structures with only
      one bound cation. The inter-quartet cavities at the inversion of polarity sites
      bind ammonium ions less tightly than a naturally occurring 5'-3' backbone.
      Exchange of (15)  ions between G-quadruplex and bulk solution is faster at the 3'
      end in comparison to the 5'-end. In addition to strand directionality, cation
      movement is influenced by formation of an all-syn G-quartet. Formation of such
      quartet has been observed also for the parent d(TG(3)T) that besides the
      canonical quadruplex with only all-anti G-quartets, forms a tetramolecular
      parallel quadruplex containing one all-syn G-quartet, never observed before in
      unmodified quadruplex structures.

PMID- 22977178
TI  - Circular retrotransposition products generated by a LINE retrotransposon.
AB  - Non-long terminal repeat (non-LTR) retrotransposons are highly abundant elements
      that are present in chromosomes throughout the eukaryotic domain of life. The
      long interspersed nuclear element (LINE-1) (L1) clade of non-LTR retrotransposons
      has been particularly successful in mammals, accounting for 30-40% of human
      genome sequence. The current model of LINE retrotransposition, target-primed
      reverse transcription, culminates in a chromosomally integrated end product.
      Using a budding yeast model of non-LTR retrotransposition, we show that in
      addition to producing these 'classical', chromosomally integrated products, a
      fungal L1 clade member (Zorro3) can generate abundant, RNA-derived episomal
      products. Genetic evidence suggests that these products are likely to be formed
      via a variation of target-primed reverse transcription. These episomal products
      are a previously unseen alternative fate of LINE retrotransposition, and may
      represent an unexpected source for de novo retrotransposition.

PMID- 22977179
TI  - The GyrA-box determines the geometry of DNA bound to gyrase and couples DNA
      binding to the nucleotide cycle.
AB  - DNA gyrase catalyses the adenosine triphosphate-dependent introduction of
      negative supercoils into DNA. The enzyme binds a DNA-segment at the so-called DNA
      gate and cleaves both DNA strands. DNA extending from the DNA-gate is bound at
      the perimeter of the cylindrical C-terminal domains (CTDs) of the GyrA subunit.
      The CTDs are believed to contribute to the wrapping of DNA around gyrase in a
      positive node as a prerequisite for strand passage towards negative supercoiling.
      A conserved seven amino acid sequence motif in the CTD, the so-called GyrA-box,
      has been identified as a hallmark feature of gyrases. Mutations of the GyrA-box
      abolish supercoiling. We show here that the GyrA-box marginally stabilizes the
      CTDs. Although it does not contribute to DNA binding, it is required for DNA
      bending and wrapping, and it determines the geometry of the bound DNA. Mutations
      of the GyrA-box abrogate a DNA-induced conformational change of the gyrase N-gate
      and uncouple DNA binding and adenosine triphosphate hydrolysis. Our results
      implicate the GyrA-box in coordinating DNA binding and the nucleotide cycle.

PMID- 22977180
TI  - Structure of Actin-related protein 8 and its contribution to nucleosome binding.
AB  - Nuclear actin-related proteins (Arps) are subunits of several chromatin
      remodelers, but their molecular functions within these complexes are unclear. We
      report the crystal structure of the INO80 complex subunit Arp8 in its ATP-bound
      form. Human Arp8 has several insertions in the conserved actin fold that explain
      its inability to polymerize. Most remarkably, one insertion wraps over the active
      site cleft and appears to rigidify the domain architecture, while active site
      features shared with actin suggest an allosterically controlled ATPase activity.
      Quantitative binding studies with nucleosomes and histone complexes reveal that
      Arp8 and the Arp8-Arp4-actin-HSA sub-complex of INO80 strongly prefer nucleosomes
      and H3-H4 tetramers over H2A-H2B dimers, suggesting that Arp8 functions as a
      nucleosome recognition module. In contrast, Arp4 prefers free (H3-H4)(2) over
      nucleosomes and may serve remodelers through binding to (dis)assembly
      intermediates in the remodeling reaction.

PMID- 22977181
TI  - FRETmatrix: a general methodology for the simulation and analysis of FRET in
      nucleic acids.
AB  - Forster resonance energy transfer (FRET) is a technique commonly used to unravel
      the structure and conformational changes of biomolecules being vital for all
      living organisms. Typically, FRET is performed using dyes attached externally to
      nucleic acids through a linker that complicates quantitative interpretation of
      experiments because of dye diffusion and reorientation. Here, we report a
      versatile, general methodology for the simulation and analysis of FRET in nucleic
      acids, and demonstrate its particular power for modelling FRET between probes
      possessing limited diffusional and rotational freedom, such as our recently
      developed nucleobase analogue FRET pairs (base-base FRET). These probes are
      positioned inside the DNA/RNA structures as a replacement for one of the natural
      bases, thus, providing unique control of their position and orientation and the
      advantage of reporting from inside sites of interest. In demonstration studies,
      not requiring molecular dynamics modelling, we obtain previously inaccessible
      insight into the orientation and nanosecond dynamics of the bases inside double
      stranded DNA, and we reconstruct high resolution 3D structures of kinked DNA. The
      reported methodology is accompanied by a freely available software package,
      FRETmatrix, for the design and analysis of FRET in nucleic acid containing
      systems.

PMID- 22977182
TI  - Context-specific microRNA analysis: identification of functional microRNAs and
      their mRNA targets.
AB  - MicroRNAs (miRs) function primarily as post-transcriptional negative regulators
      of gene expression through binding to their mRNA targets. Reliable prediction of
      a miR's targets is a considerable bioinformatic challenge of great importance for
      inferring the miR's function. Sequence-based prediction algorithms have high
      false-positive rates, are not in agreement, and are not biological context
      specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an
      algorithm that combines sequence-based prediction with miR and mRNA expression
      data. CoSMic differs from existing methods--it identifies miRs that play active
      roles in the specific biological system of interest and predicts with less false
      positives their functional targets. We applied CoSMic to search for miRs that
      regulate the migratory response of human mammary cells to epidermal growth factor
      (EGF) stimulation. Several such miRs, whose putative targets were significantly
      enriched by migration processes were identified. We tested three of these miRs
      experimentally, and showed that they indeed affected the migratory phenotype; we
      also tested three negative controls. In comparison to other algorithms CoSMic
      indeed filters out false positives and allows improved identification of context
      specific targets. CoSMic can greatly facilitate miR research in general and, in
      particular, advance our understanding of individual miRs' function in a specific
      context.

PMID- 22977184
TI  - 'Innovation' in health care coverage decisions: all talk and no substance?
AB  - There has been much discussion recently about 'innovation', or more precisely the
      lack of it, in pharmaceuticals and devices in health care. The concern has been
      expressed by national guideline bodies, such as the Common Drugs Review in Canada
      and the National Institute for Health & Clinical Excellence in the UK, applying
      strict cost-effectiveness criteria in their decision-making and, therefore,
      failing adequately to recognize the full benefits that come from innovation. In
      order to explore the legitimacy of such claims, we first define innovation, and
      second, explore the basis for assuming an independent and separable social value
      associated with innovation. We conclude that demands relating to innovation, such
      as relaxation of thresholds and premium prices for innovatory products, remain
      hollow until we have a compelling case on the demand side for a separable social
      value on 'innovation'. We see no such case currently.

PMID- 22977185
TI  - Cohort study of the association of hypnotic use with mortality in postmenopausal
      women.
AB  - OBJECTIVE: Previous studies found an association between hypnotic use and
      mortality risk. The prospective outcome data and the many baseline risk factors
      included in the Women's Health Initiative (WHI) provide an opportunity to better
      understand the reasons for this association. SETTING: The WHI is a long-term
      national health study that focused on strategies for preventing disease in
      postmenopausal women. Participants were enrolled from 1993 to 1998. DESIGN:
      Baseline hypnotic use was evaluated for an association with subsequent mortality
      or disease after adjusting for baseline risk. SUBJECTS: 148 938 postmenopausal
      women between the ages of 50 and 79 throughout the USA. The median follow-up was
      8 years. MAIN OUTCOME MEASURES: Mortality. Secondary outcomes included myocardial
      infarction, stroke, diabetes and seven types of cancer. RESULTS: For persons who
      use hypnotic medications almost daily the age-adjusted hazard ratio (HR) for
      mortality was 1.62 (95% CI 1.50 to 1.74). Greater hypnotic use was associated
      with less healthy levels of physical function, general health and smoking at
      baseline. After adjustment for these factors the HR for almost daily hypnotic use
      was 1.14 (1.06 to 1.23) for mortality and 1.53 (1.18 to 1.99) for melanoma; it
      was not significantly associated with increased incidence of other diseases
      tested. Less frequent hypnotic use and several types of sleeping difficulties
      were not associated with mortality, but sleeping more than 10 h a night had a
      risk-adjusted HR for mortality of 1.28 (1.01 to 1.61). CONCLUSIONS: The
      association of hypnotic use with mortality and incident disease was greatly
      reduced after adjusting for baseline risk factors. These findings do not support
      a strong independent association of hypnotic use with most health outcomes.

PMID- 22977186
TI  - Correction.

PMID- 22977183
TI  - Direct mapping of symbolic DNA sequence into frequency domain in global repeat
      map algorithm.
AB  - The main feature of global repeat map (GRM) algorithm
      (www.hazu.hr/grm/software/win/grm2012.exe) is its ability to identify a broad
      variety of repeats of unbounded length that can be arbitrarily distant in
      sequences as large as human chromosomes. The efficacy is due to the use of
      complete set of a K-string ensemble which enables a new method of direct mapping
      of symbolic DNA sequence into frequency domain, with straightforward
      identification of repeats as peaks in GRM diagram. In this way, we obtain very
      fast, efficient and highly automatized repeat finding tool. The method is robust
      to substitutions and insertions/deletions, as well as to various complexities of
      the sequence pattern. We present several case studies of GRM use, in order to
      illustrate its capabilities: identification of alpha-satellite tandem repeats and
      higher order repeats (HORs), identification of Alu dispersed repeats and of Alu
      tandems, identification of Period 3 pattern in exons, implementation of
      'magnifying glass' effect, identification of complex HOR pattern, identification
      of inter-tandem transitional dispersed repeat sequences and identification of
      long segmental duplications. GRM algorithm is convenient for use, in particular,
      in cases of large repeat units, of highly mutated and/or complex repeats, and of
      global repeat maps for large genomic sequences (chromosomes and genomes).

PMID- 22977187
TI  - Musculoskeletal disorders among municipal solid waste collectors in Mansoura,
      Egypt: a cross-sectional study.
AB  - OBJECTIVE: To assess the percentage of musculoskeletal complaints and their
      possible risk factors among municipal solid waste (MSW) collectors. DESIGN: A
      descriptive cross-sectional study with a comparison group. SETTING: Primary level
      of care, at the Western Municipality of Mansoura City, Egypt. PARTICIPANTS: A
      total of 160 male MSW collectors fulfilled the eligibility criteria and 120 of
      them participated in the study (response rate of 75%). The inclusion criteria
      were permanent or temporary solid waste collectors employed for 1 year or more. A
      comparison group of 110 male service workers at the Faculty of Medicine, Mansoura
      University, comparable to MSW collectors in most of the variables. OUTCOME: The
      percentage of musculoskeletal disorders (MSDs) among collectors, their risk
      factors (socio-demographic, psychosocial, physical), and the independent risk
      factors for having the disorders. RESULTS: The percentage of musculoskeletal
      complaints during the past 12 months was higher among MSW collectors (60.8%) than
      the comparison group (43.6%). Low back was the most frequently affected body
      region among MSW collectors. The differences in the distribution of
      musculoskeletal complaints between the two groups were statistically significant
      for the neck and hip/thigh regions. Logistic regression analysis revealed that
      the independent risk factors for musculoskeletal symptoms among MSW collectors
      were the longer duration of employment (OR=0.4, 95% CI=0.1 to 0.9); low decision
      latitude (OR=0.3, 95% CI=0.1 to 0.7); lifting, pulling; pushing/carrying loads
      >20 kg (OR=5.5, 95% CI=1.8 to 17.0) and walking for long periods of time (OR=2.6,
      95% CI=1.1 to 6.6). CONCLUSIONS: Musculoskeletal complaints are highly prevalent
      among MSW collectors which require engineering, medical and legislative measures.
      We suggest further research in the interventions that could reduce the high
      percentage among collectors.

PMID- 22977188
TI  - AACR Cancer Progress Report 2012.

PMID- 22977189
TI  - Gauging progress in a decades-old fight.

PMID- 22977190
TI  - Predictors of survival in never-smokers with non-small cell lung cancer: a large
      scale, two-phase genetic study.
AB  - PURPOSE: Lung cancer in never-smokers (LCINS) is increasingly recognized as a
      distinct disease from that in ever-smokers owing to substantial differences in
      etiology, clinical characteristics, and prognosis. Therefore, we aimed to
      identify prognostic markers specific for LCINS. EXPERIMENTAL DESIGN: First,
      11,930 single-nucleotide polymorphisms (SNP) in 904 inflammation-related genes
      were genotyped, and their associations with overall survival in 411 patients with
      LCINS at MD Anderson Cancer Center were analyzed. Next, validation of the top 27
      SNPs in 311 patients with LCINS at Mayo Clinic was conducted. RESULTS: Three SNPs
      (IL17RA:rs879576, BMP8A:rs698141, and STY:rs290229) were validated (P < 0.05),
      and two SNPs (CD74:rs1056400 and CD38:rs10805347) reached borderline significance
      (P = 0.08) in the Mayo Clinic population. We validated a survival-tree created in
      the MD Anderson population exploring gene-gene interactions in the Mayo Clinic
      population. This survival-tree stratified patients into subsets with
      significantly different risks of death: patients with the
      rs1056400_GG/rs698141_GA + AA genotype had significantly higher risk of death in
      both MD Anderson (HR:2.32, 95%CI: 1.58-3.41) and Mayo (HR:1.97, 95%CI: 1.11-3.50)
      populations compared with those with the rs1056400_GG/rs698141_GG or rs1056400_GA
      + AA genotype. We evaluated these five SNPs in 996 ever-smokers from MD Anderson
      and found no significant associations. CONCLUSIONS: Our study provides strong
      evidence that inflammation-related genetic variations can affect clinical
      outcomes in LCINS, which may lead to significant biologic insight into these
      outcomes.

PMID- 22977191
TI  - Phase II clinical and pharmacokinetic study of aflibercept in patients with
      previously treated metastatic colorectal cancer.
AB  - PURPOSE: Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR)
      1 and VEGFR2 extracellular domains. We assessed the safety and efficacy of
      aflibercept in patients with metastatic colorectal cancer (MCRC) who had received
      at least one prior palliative regimen. EXPERIMENTAL DESIGN: Seventy-five patients
      were enrolled onto this two-stage phase II trial in two cohorts, bevacizumab
      naive (n = 24) and prior bevacizumab (n = 51). Aflibercept was administered at 4
      mg/kg i.v. in two-week cycles. The primary endpoint was a combination of
      objective response rate and 16-week progression-free survival (PFS). RESULTS: In
      the bevacizumab-naive cohort (n = 24), the best response was stable disease for
      16 weeks or more in five of 24 patients. In the prior bevacizumab cohort (n =
      50), one patient achieved a partial response and six patients had stable disease
      for 16 weeks or more. The median PFS in the bevacizumab-naive and prior
      bevacizumab cohorts was two months [95% confidence interval (CI): 1.7-8.6 months]
      and 2.4 months (95% CI: 1.9-3.7 months), respectively. Median overall survival
      (OS) was 10.4 months (95% CI: 7.6-15.5) and 8.5 months (95% CI: 6.2-10.6),
      respectively. The most common grade 3 or higher treatment-related adverse events
      were hypertension, proteinuria, fatigue, and headache. Ten patients discontinued
      study treatment due to toxicity. Mean free to VEGF-bound aflibercept ratio was
      1.82, suggesting that free aflibercept was present in sufficient amount to bind
      endogenous VEGF. CONCLUSION: Aflibercept showed limited single-agent activity in
      patients with pretreated MCRC with moderate toxicity. Further study of
      aflibercept with chemotherapy is ongoing.

PMID- 22977192
TI  - Overexpression of ecdysoneless in pancreatic cancer and its role in oncogenesis
      by regulating glycolysis.
AB  - PURPOSE: To study the expression and function of a novel cell-cycle regulatory
      protein, human ecdysoneless (Ecd), during pancreatic cancer pathogenesis.
      EXPERIMENTAL DESIGN: Immunohistochemical expression profiling of Ecd was done in
      nonneoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma
      lesions (from tissue microarray and Rapid Autopsy program) as well as
      precancerous PanIN lesions and metastatic organs. To analyze the biological
      significance of Ecd in pancreatic cancer progression, Ecd was stably knocked down
      in pancreatic cancer cell line followed by in vitro and in vivo functional
      assays. RESULTS: Normal pancreatic ducts showed very weak to no Ecd expression
      compared to significant positive expression in pancreatic cancer tissues (mean +/
      SE composite score: 0.3 +/- 0.2 and 3.8 +/- 0.2 respectively, P < 0.0001) as
      well as in PanIN precursor lesions with a progressive increase in Ecd expression
      with increasing dysplasia (PanIN-1-PanIN-3). Analysis of matched primary tumors
      and metastases from patients with pancreatic cancer revealed that Ecd is highly
      expressed in both primary pancreatic tumor and in distant metastatic sites.
      Furthermore, knockdown of Ecd suppressed cell proliferation in vitro and
      tumorigenicity of pancreatic cancer cells in mice orthotopic tumors. Microarray
      study revealed that Ecd regulates expression of glucose transporter GLUT4 in
      pancreatic cancer cells and was subsequently shown to modulate glucose uptake,
      lactate production, and ATP generation by pancreatic cancer cells. Finally,
      knockdown of Ecd also reduced level of pAkt, key signaling molecule known to
      regulate aerobic glycolysis in cancer cells. CONCLUSION: Ecd is a novel tumor
      promoting factor that is differentially expressed in pancreatic cancer and
      potentially regulates glucose metabolism within cancer cells.

PMID- 22977193
TI  - Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on
      survival in stage II/III gastric cancer.
AB  - PURPOSE: EGF receptor (EGFR) and HER2 positivity are considered to be negative
      prognostic factors in gastric cancer. Biomarker analysis was conducted to
      evaluate the impact of EGFR and HER2 expression on the outcome of patients
      enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC),
      a randomized controlled trial comparing postoperative adjuvant S-1 therapy with
      surgery alone in 1,059 patients with stage II/III gastric cancer. EXPERIMENTAL
      DESIGN: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively
      examined in 829 patients (78.3%). The effects of EGFR and HER2 positivity on
      survival were analyzed on the basis of the 5-year survival data from the study.
      EGFR positivity was defined as an immunohistochemistry (IHC) score of 3+, and
      HER2 positivity as an IHC score of 3+ or an IHC score of 2+ with a positive dual
      color in situ hybridization status. RESULTS: EGFR and HER2 were positive in 75
      (9.0%) and 113 (13.6%) patients, respectively. The overall and relapse-free
      survival rates were significantly lower in EGFR-positive patients than in EGFR
      negative patients, whereas they were similar in HER2-positive and HER2-negative
      patients. Multivariate analysis showed that EGFR positivity correlated with poor
      outcomes [HR = 1.504; 95% confidence interval (CI) = 1.020-2.149; P = 0.040].
      Treatment with S-1 improved survival compared with surgery alone, irrespective of
      EGFR and HER2 status. CONCLUSIONS: EGFR positivity, but not HER2 positivity, was
      associated with poor patient outcomes after curative resection of stage II/III
      gastric cancer. There was no interaction between S-1 and EGFR or HER2 status with
      respect to survival outcome.

PMID- 22977194
TI  - FoxM1 inhibition sensitizes resistant glioblastoma cells to temozolomide by
      downregulating the expression of DNA-repair gene Rad51.
AB  - PURPOSE: Recurrent glioblastoma multiforme (GBM) is characterized by resistance
      to radiotherapy and chemotherapy and a poor clinical prognosis. In this study, we
      investigated the role of the oncogenic transcription factor FoxM1 in GBM cells'
      resistance to alkylator temozolomide (TMZ) and its potential molecular mechanism.
      EXPERIMENTAL DESIGN: FoxM1 expression levels were measured by immunohistochemical
      analysis in 38 pairs of primary and recurrent GBM tumor samples. Expression
      levels were also measured in primary recurrent GBM cell lines, and their
      responses to TMZ were characterized. In a mechanistic study, an siRNA array was
      used to identify downstream genes, and a chromatin immunoprecipitation assay was
      used to confirm transcriptional regulation. RESULTS: Recurrent tumors that were
      TMZ resistant expressed higher levels of FoxM1 than did primary tumors. Recurrent
      GBM cell lines expressed higher levels of FoxM1 and the DNA damage repair gene
      Rad51 and were resistant to TMZ. TMZ treatment led to increased FoxM1 and Rad51
      expression. FoxM1 knockdown inhibited Rad51 expression and sensitized recurrent
      GBM cells to TMZ cytotoxicity. FoxM1 directly regulated Rad51 expression through
      2 FoxM1-specific binding sites in its promoter. Rad51 reexpression partially
      rescued TMZ resistance in FoxM1-knockdown recurrent GBM cells. A direct
      correlation between FoxM1 expression and Rad51 expression was evident in
      recurrent GBM tumor samples. CONCLUSION: Targeting the FoxM1-Rad51 axis may be an
      effective method to reverse TMZ resistance in recurrent GBM.

PMID- 22977196
TI  - The use of teleglaucoma at the University of Alberta.
AB  - The aim of the teleglaucoma service at the University of Alberta is to improve
      access for people in northern Alberta who have early-stage glaucoma or who are at
      risk for glaucoma. Two types of teleglaucoma service are offered: remote and in
      house. A standardized approach is used to capture patient information (structured
      histories, examinations and fundus photographs) which is then sent to a tertiary
      care centre for grading and recommendations. Only one grader reads and makes
      management recommendations for each case. Reports are sent electronically. A
      total of 195 cases have been graded through the remote service since 2008. A
      total of 62 cases have been graded through the in-house service since 2011. The
      average reporting time for consultations in the in-house service was 7 days, and
      it was also 7 days for the remote service. We believe that the use of
      teleglaucoma can improve the way that patients are diagnosed and managed, both in
      industrialized and developing countries. Teleglaucoma is currently being used as
      a screening tool at the Aga Khan University Hospital in Nairobi with mobile units
      equipped with a fundus camera and a visual field machine.

PMID- 22977195
TI  - Efficacy of cetuximab in metastatic castration-resistant prostate cancer might
      depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07).
AB  - PURPOSE: The EGF receptor (EGFR) is overexpressed in the majority of metastatic
      castration-resistant prostate cancers (mCRPC) and might represent a valid
      therapeutic target. The combination of docetaxel and cetuximab, the monoclonal
      antibody against EGFR, has not been tested in patients with prostate cancer.
      EXPERIMENTAL DESIGN: Patients with mCRPC progressing during or within 90 days
      after at least 12 weeks of docetaxel were included in this phase II trial.
      Treatment consisted of docetaxel (75 mg/m(2) every 3 weeks or 35 mg/m(2) on days
      1, 8, 15 every 4 weeks) in combination with cetuximab (400 mg/m(2) on day 1 and
      then 250 mg/m(2) weekly). The primary endpoint was progression-free survival
      (PFS) at 12 weeks defined as the absence of prostate-specific antigen (PSA),
      radiographic, or clinical progression. Evaluation of known biomarkers of response
      and resistance to cetuximab (EGFR, PTEN, amphiregulin, epiregulin) was conducted.
      RESULTS: Thirty-eight patients were enrolled at 15 Swiss centers. Median age was
      68 years and median PSA was 212 ng/mL. PFS at 12 weeks was 34% [95% confidence
      interval (CI), 19%-52%], PFS at 24 weeks was 20%, and median overall survival
      (OS) was 13.3 months (95% CI, 7.3-15.4). Seven patients (20%) had a confirmed >=
      50% and 11 patients (31%) a confirmed >= 30% PSA decline. About 47% of enrolled
      patients experienced grade 3 and 8% grade 4 toxicities. A significantly improved
      PFS was found in patients with overexpression of EGFR and persistent activity of
      PTEN. CONCLUSIONS: EGFR inhibition with cetuximab might improve the outcome of
      patients with mCRPC. A potential correlation between EGFR overexpression,
      persistent expression of PTEN, and EGFR inhibition should be investigated
      further.

PMID- 22977197
TI  - Severity of injury and the decision to arrest in cases of intimate partner
      violence.
AB  - From a victim's physical health perspective, at the centre of any case of
      intimate partner violence (IPV) is the degree of trauma imparted on that victim
      by the offender. Yet, the implementations of state-level 'Mandatory Arrest' and
      'Preferred Arrest' laws encourage arrests decisions in cases of IPV typically
      without regard to the level of trauma severity found in each case. And, despite
      these well-meaning implementations and the gravity of their consequences, the
      importance of evaluating trauma severity in victims of IPV remains largely
      overlooked. The goal of this study was to correlate police arrest decisions in
      cases of IPV to a trauma severity score generated from established clinical
      protocols in the treatment of trauma. A Trauma Severity Quantification Table
      (TSQT) was created in order to quantify the major factors of an incident of IPV:
      anatomical location of attack, method of attack, facilitating weapon/object and
      resulting trauma. A total of 256 cases of IPV reported to six police departments
      in Idaho, a state with a discretionary arrest law in domestic violence cases, in
      the calendar year 2000 were processed using the TSQT. A statistically significant
      difference was found between arrests (mean 17.96, standard deviation [SD] 5.90)
      versus no arrest (mean 16.13, SD 5.67) outcomes (P = 0.03). It is suggested that
      trauma severity is a factor in police arrest decisions in a discretionary state
      sample, but that more attention needs to be brought to this method of analysis
      and its implications for future arrest decisions.

PMID- 22977198
TI  - Functional brain networks and white matter underlying theory-of-mind in autism.
AB  - Human beings constantly engage in attributing causal explanations to one's own
      and to others' actions, and theory-of-mind (ToM) is critical in making such
      inferences. Although children learn causal attribution early in development,
      children with autism spectrum disorders (ASDs) are known to have impairments in
      the development of intentional causality. This functional magnetic resonance
      imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural
      correlates of physical and intentional causal attribution in people with ASDs. In
      the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched
      typically developing peers made causal judgments about comic strips presented
      randomly in an event-related design. All participants showed robust activation in
      bilateral posterior superior temporal sulcus at the temporo-parietal junction
      (TPJ) in response to intentional causality. Participants with ASDs showed lower
      activation in TPJ, right inferior frontal gyrus and left premotor cortex.
      Significantly weaker functional connectivity was also found in the ASD group
      between TPJ and motor areas during intentional causality. DTI data revealed
      significantly reduced fractional anisotropy in ASD participants in white matter
      underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM,
      this study found an interaction between motor simulation and mentalizing systems
      in intentional causal attribution and its possible discord in autism. 

PMID- 22977199
TI  - Anterior insular cortex mediates bodily sensibility and social anxiety.
AB  - Studies in psychiatry and cognitive neuroscience have reported an important
      relationship between individual interoceptive accuracy and anxiety level. This
      indicates that greater attention to one's bodily state may contribute to the
      development of intense negative emotions and anxiety disorders. We hypothesized
      that reactivity in the anterior insular cortex underlies the intensity of
      interoceptive awareness and anxiety. To elucidate this triadic mechanism, we
      conducted functional magnetic resonance imaging (fMRI) and mediation analyses to
      examine the relationship between emotional disposition and activation in the
      anterior insular cortex while participants evaluated their own emotional and
      bodily states. Our results indicated that right anterior insular activation was
      positively correlated with individual levels of social anxiety and neuroticism
      and negatively correlated with agreeableness and extraversion. The results of the
      mediation analyses revealed that activity in the right anterior insula mediated
      the activity of neural correlates of interoceptive sensibility and social fear.
      Our findings suggest that attention to interoceptive sensation affects
      personality traits through how we feel emotion subjectively in various
      situations.

PMID- 22977200
TI  - Effect of direct eye contact in PTSD related to interpersonal trauma: an fMRI
      study of activation of an innate alarm system.
AB  - In healthy individuals, direct eye contact initially leads to activation of a
      fast subcortical pathway, which then modulates a cortical route eliciting social
      cognitive processes. The aim of this study was to gain insight into the
      neurobiological effects of direct eye-to-eye contact using a virtual reality
      paradigm in individuals with posttraumatic stress disorder (PTSD) related to
      prolonged childhood abuse. We examined 16 healthy comparison subjects and 16
      patients with a primary diagnosis of PTSD using a virtual reality functional
      magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad,
      neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed
      emotion, controls exhibited an increased blood oxygenation level-dependent
      response during direct vs averted gaze within the dorsomedial prefrontal cortex,
      left temporoparietal junction and right temporal pole. Under the same conditions,
      individuals with PTSD showed increased activation within the superior colliculus
      (SC)/periaqueductal gray (PAG) and locus coeruleus. Our findings suggest that
      healthy controls react to the exposure of direct gaze with an activation of a
      cortical route that enhances evaluative 'top-down' processes underlying social
      interactions. In individuals with PTSD, however, direct gaze leads to sustained
      activation of a subcortical route of eye-contact processing, an innate alarm
      system involving the SC and the underlying circuits of the PAG. 

PMID- 22977202
TI  - Loss in the NICU: sibling matters.
AB  - Siblings of patients that have lengthy stays in the neonatal intensive care unit
      (NICU) may be affected emotionally by their brother's or sister's condition,
      separation, or even death. In an effort to assess the effect of perinatal loss on
      siblings a student-led inquiry was designed and tested. A scripted interview was
      composed to determine whether or not children were effectively processing the
      loss of their sibling. While a single case is reported, the methodology proved
      useful and opens the door to further consideration of providing sibling-oriented
      grief and bereavement services in the NICU. 

PMID- 22977201
TI  - Modulation of affective face processing deficits in Schizophrenia by congruent
      emotional sounds.
AB  - Schizophrenia is a psychiatric disorder resulting in prominent impairments in
      social functioning. Thus, clinical research has focused on underlying deficits of
      emotion processing and their linkage to specific symptoms and neurobiological
      dysfunctions. Although there is substantial research investigating impairments in
      unimodal affect recognition, studies in schizophrenia exploring crossmodal
      emotion processing are rare. Therefore, event-related potentials were measured in
      15 patients with schizophrenia and 15 healthy controls while rating the
      expression of happy, fearful and neutral faces and concurrently being distracted
      by emotional or neutral sounds. Compared with controls, patients with
      schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in
      response to all faces, independent of emotion or concurrent sound. Analyzing
      these effects with regard to audiovisual (in)congruence revealed that P1
      amplitudes in patients were only reduced in response to emotionally incongruent
      stimulus pairs, whereas similar amplitudes between groups could be observed for
      congruent conditions. Correlation analyses revealed a significant negative
      correlation between general symptom severity (Brief Psychiatric Rating Scale-V4)
      and P1 amplitudes in response to congruent audiovisual stimulus pairs. These
      results indicate that early visual processing deficits in schizophrenia are
      apparent during emotion processing but, depending on symptom severity, these
      deficits can be restored by presenting concurrent emotionally congruent sounds. 

PMID- 22977203
TI  - Two decades of sunfleck research: looking back to move forward.

PMID- 22977204
TI  - Modelling photosynthesis in highly dynamic environments: the case of sunflecks.

PMID- 22977205
TI  - Differences in ascorbate and glutathione levels as indicators of resistance and
      susceptibility in Eucalyptus trees infected with Phytophthora cinnamomi.
AB  - In this study we investigated the role that ascorbate (AA) and glutathione (GSH)
      play in the plant pathogen interaction of susceptible Eucalyptus sieberi L. A.
      Johnson and resistant Eucalyptus sideroxylon Woolls with Phytophthora cinnamomi
      Rands root infection. In a glasshouse study, seedlings were grown in soil-free
      plant boxes to facilitate the inoculation of the root systems by a P. cinnamomi
      zoospore solution. Ascorbate and GSH concentrations were measured in infected
      roots and leaves, along with leaf gas exchange, chlorophyll fluorescence and
      carbohydrate concentrations over a time course up to 312 h (13 days) post
      inoculation (pi). At the early stages of infection (from 24 h pi), significant
      decreases in AA and GSH concentrations were observed in the infected roots and
      leaves of the susceptible E. sieberi seedlings. At the later stage of infection
      (312 h pi), the earlier AA decreases in the leaves of infected plants had become
      significant increases. In contrast, late, significant AA increases in the absence
      of any GSH changes were observed in the infected roots of the resistant E.
      sideroxylon seedlings. In E. sideroxylon leaves, a significant GSH increase
      occurred at 24 h pi; however, by 312 h pi the earlier increase had become a
      significant decrease, while no changes occurred in AA. In E. sieberi,
      photosynthesis (A), stomatal conductance (g(s)) and PSII quantum efficiency
      (Phi(PSII)) were reduced by ~60, 80 and 30%, respectively, in infected plants and
      remained significantly lower than uninfected controls for the duration of the
      experiment. Significant reductions in these parameters did not occur until later
      (120 h pi for g(s) and 312 h pi for A and Phi(PSII)), and to a lesser extent in
      the resistant species. Non-structural carbohydrate analysis of roots and leaves
      indicate that carbohydrate metabolism and resource flow between shoots and roots
      may have been altered at later infection stages. This study suggests that reduced
      antioxidant capacity, leaf physiological function and carbohydrate metabolism are
      associated with susceptibility in E. sieberi to P. cinnamomi infection, while AA
      increases and new root formation were associated with resistance in E.
      sideroxylon.

PMID- 22977207
TI  - Effects of prosthetic mass distribution on metabolic costs and walking symmetry.
AB  - Unilateral, transtibial amputees exhibit walking asymmetries and higher metabolic
      costs of walking than nonamputees walking at similar speeds. Using lightweight
      prostheses has previously been suggested as a contributing factor to walking
      asymmetries. The purpose was to investigate the effects of prosthesis mass and
      mass distribution on metabolic costs and walking asymmetries among six
      unilateral, transtibial amputees. Kinematic and temporal symmetry did not improve
      when mass was added at different locations on the limb. Stance and swing time
      asymmetries increased by 3.4% and 7.2%, respectively, with loads positioned
      distally on the limb. Maximum knee angular velocity asymmetries increased by 6%
      with mass added to the thigh, whereas maximum thigh angular velocity asymmetries
      increased by approximately 10% with mass positioned near the prosthetic ankle.
      Adding 100% of the estimated mass difference between intact and prosthetic legs
      to the ankle of the prosthesis increased energy costs of walking by 12%; adding
      the same mass to the prosthesis center of mass or thigh center of mass increased
      metabolic cost by approximately 7% and 5%, respectively. Unless other benefits
      are gained by increasing prosthesis mass, this should not be considered as a
      possible alternative to current lightweight prosthesis designs currently being
      prescribed to unilateral amputees. 

PMID- 22977206
TI  - The epidemiology of pediatric bone and joint infections in Cambodia, 2007-11.
AB  - There are limited data on osteoarticular infections from resource-limited
      settings in Asia. A retrospective study of patients presenting to the Angkor
      Hospital for Children, Cambodia, January 2007-July 2011, identified 81 cases (28%
      monoarticular septic arthritis, 51% single-limb osteomyelitis and 15% multisite
      infections). The incidence was 13.8/100 000 hospital attendances. The median age
      was 7.3 years, with a male/female ratio of 1.9:1; 35% presented within 5 days of
      symptom onset (median 7 days). Staphylococcus aureus was cultured in 29 (36%)
      cases (52% of culture-positive cases); one isolate was methicillin-resistant
      (MRSA). Median duration of antimicrobial treatment was 29 days (interquartile
      range 21-43); rates of surgical intervention were 96%, and 46% of children had
      sequelae, with one fatality. In this setting osteoarticular infections are
      relatively common with high rates of surgical intervention and sequelae.
      Staphylococcus aureus is the commonest culturable cause, but methicillin
      resistant S. aureus is not a major problem, unlike in other Asian centers.

PMID- 22977208
TI  - Dialysis dose scaled to body surface area and size-adjusted, sex-specific patient
      mortality.
AB  - BACKGROUND AND OBJECTIVES: When hemodialysis dose is scaled to body water (V),
      women typically receive a greater dose than men, but their survival is not better
      given a similar dose. This study sought to determine whether rescaling dose to
      body surface area (SA) might reveal different associations among dose, sex, and
      mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Single-pool Kt/V
      (spKt/V), equilibrated Kt/V, and standard Kt/V (stdKt/V) were computed using urea
      kinetic modeling on a prevalent cohort of 7229 patients undergoing thrice-weekly
      hemodialysis. Data were obtained from the Centers for Medicare & Medicaid
      Services 2008 ESRD Clinical Performance Measures Project. SA-normalized stdKt/V
      (SAN-stdKt/V) was calculated as stdKt/V * ratio of anthropometric volume to
      SA/17.5. Patients were grouped into sex-specific dose quintiles (reference:
      quintile 1 for men). Adjusted hazard ratios (HRs) for 1-year mortality were
      calculated using Cox regression. RESULTS: spKt/V was higher in women (1.7 +/-
      0.3) than in men (1.5 +/- 0.2; P<0.001), but SAN-stdKt/V was lower (women: 2.3 +/
      0.2; men: 2.5 +/- 0.3; P<0.001). For both sexes, mortality decreased as spKt/V
      increased, until spKt/V was 1.6-1.7 (quintile 4 for men: HR, 0.62; quintile 3 for
      women: HR, 0.64); no benefit was observed with higher spKt/V. HR for mortality
      decreased further at higher SAN-stdKt/V in both sexes (quintile 5 for men: HR,
      0.69; quintile 5 for women: HR, 0.60). CONCLUSIONS: SA-based dialysis dose
      results in dose-mortality relationships substantially different from those with
      volume-based dosing. SAN-stdKt/V analyses suggest women may be relatively
      underdosed when treated by V-based dosing. SAN-stdKt/V as a measure for dialysis
      dose may warrant further study.

PMID- 22977210
TI  - Nephrology and the percutaneous renal biopsy: a procedure in jeopardy of being
      lost along the way.

PMID- 22977209
TI  - Carotid intima-media thickness in children with CKD: results from the CKiD study.
AB  - BACKGROUND AND OBJECTIVES: In adults, increased carotid intima-media thickness
      (cIMT) as assessed by ultrasonography is a valid predictor of cardiovascular
      events. Children with CKD are known to be at increased cardiovascular risk. This
      study sought to identify cardiovascular risk factors associated with increased
      cIMT in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      was a cross-sectional analysis of cIMT obtained after 12 months of follow-up of
      101 children aged 2-18 years with mild to moderate CKD (median GFR 42.9 ml/min
      per 1.73 m(2)) in the Chronic Kidney Disease in Children cohort study enrolled
      between April 2005 and September 2009 and 97 healthy pediatric controls between
      January 2003 and December 2008. An average of six standardized B-mode ultrasound
      measurements constituted the overall cIMT measurement. RESULTS: The median cIMT
      was 0.43 mm (interquartile range, 0.38-0.48) compared with 0.41 mm in healthy
      controls (P=0.03 for difference). After multivariable adjustment, the median cIMT
      was 0.02 mm (95% confidence interval [CI], 0.01-0.05) larger than that of the
      healthy controls. In a multivariable linear regression analysis, dyslipidemia and
      hypertension were associated with 0.05 mm (95% CI, 0.01-0.08) and 0.04 mm (95%
      CI, 0.003-0.08) greater mean cIMT, respectively. Body mass index, CKD etiology,
      GFR, birth weight, pubertal status, calcium, phosphorus, sex, and race were not
      associated with cIMT. CONCLUSIONS: cIMT is significantly elevated among children
      with CKD, as is the prevalence of other cardiovascular risk factors. Of these
      risk factors, hypertension and dyslipidemia are significantly associated with
      increased cIMT.

PMID- 22977211
TI  - Accessing the access.

PMID- 22977212
TI  - ESRD Networks: past, present, and challenges for the future.
AB  - Established by Federal law in 1978, the ESRD Networks are regional nonprofit
      organizations that contract with the Centers for Medicare and Medicaid Services
      to provide quality oversight services to chronic dialysis facilities. The
      governing bodies and medical review boards of each network are populated by
      volunteer professionals and patients. The medical review boards drive the quality
      agenda for each network, addressing specific local barriers to improvement. The
      network contract deliverables are defined by the Centers for Medicare and
      Medicaid Services in a scope of work document (SOW) that is generally revised
      with each 3-year contracting cycle. The current SOW has not been revised since
      the implementation of the new Conditions for Coverage for dialysis facilities in
      2008 or the implementation of a bundled payment system and quality incentive
      program for dialysis providers in 2011. The future success of the ESRD Network
      Program will depend upon adequate funding, data accessibility to drive rapid
      cycle quality improvement efforts, and partnerships with other stakeholder groups
      to address the continuum of care of patients with CKD. The Forum of ESRD Networks
      has developed a strategic plan that aligns the priorities of the networks with
      the National Quality Strategy. The integration of these objectives into the next
      SOW will augment the relevance of the network program to the ESRD stakeholder
      community as the networks move from a task-oriented approach to a system
      improvement approach to quality oversight.

PMID- 22977213
TI  - AKI in a patient with cirrhosis and ascites.
AB  - Acute deterioration in kidney function in a patient with cirrhosis and ascites
      presents a difficult management problem, and it is associated with increased
      mortality. In this Attending Rounds paper, a patient with oliguric AKI is
      presented to emphasize the role of laboratory and bedside tests that can
      establish a correct diagnosis and lead to appropriate management.

PMID- 22977214
TI  - Critical and honest conversations: the evidence behind the "Choosing Wisely"
      campaign recommendations by the American Society of Nephrology.
AB  - Estimates suggest that one third of United States health care spending results
      from overuse or misuse of tests, procedures, and therapies. The American Board of
      Internal Medicine Foundation, in partnership with Consumer Reports, initiated the
      "Choosing Wisely" campaign to identify areas in patient care and resource use
      most open to improvement. Nine subspecialty organizations joined the campaign;
      each organization identified five tests, procedures, or therapies that are
      overused, are misused, or could potentially lead to harm or unnecessary health
      care spending. Each of the American Society of Nephrology's (ASN's) 10 advisory
      groups submitted recommendations for inclusion. The ASN Quality and Patient
      Safety Task Force selected five recommendations based on relevance and importance
      to individuals with kidney disease.Recommendations selected were: (1) Do not
      perform routine cancer screening for dialysis patients with limited life
      expectancies without signs or symptoms; (2) do not administer erythropoiesis
      stimulating agents to CKD patients with hemoglobin levels >=10 g/dl without
      symptoms of anemia; (3) avoid nonsteroidal anti-inflammatory drugs in individuals
      with hypertension, heart failure, or CKD of all causes, including diabetes; (4)
      do not place peripherally inserted central catheters in stage 3-5 CKD patients
      without consulting nephrology; (5) do not initiate chronic dialysis without
      ensuring a shared decision-making process between patients, their families, and
      their physicians.These five recommendations and supporting evidence give
      providers information to facilitate prudent care decisions and empower patients
      to actively participate in critical, honest conversations about their care,
      potentially reducing unnecessary health care spending and preventing harm.

PMID- 22977215
TI  - Lupus nephritis: is the kidney biopsy currently necessary in the management of
      lupus nephritis?
AB  - Most patients with SLE develop kidney disease related to this systemic underlying
      disease process. Lupus nephritis is an important cause of morbidity and even
      mortality in patients with systemic lupus erythematosus. Lupus nephritis has
      diverse morphologic manifestations with varying clinical presentations and
      consequences. The pathogeneses involve immune complexes, which can deposit
      anywhere in the kidney, and other mechanisms, including endothelial injury,
      podocytopathy, and tubulointerstitial injury. Treatment and prognosis accordingly
      range from excellent even with only observation with minimal mesangial deposits,
      to kidney failure despite aggressive immunosuppression in patients with severe
      proliferative disease. Renal biopsy plays a crucial role in the diagnosis of the
      specific form of lupus nephritis in any patient. However, the role of the renal
      biopsy in prediction of outcome, treatment, and prognosis has been controversial.
      We will review the current classification of lupus nephritis and the value of
      renal biopsy in the management of these patients.

PMID- 22977217
TI  - Common infections in kidney transplant recipients.
AB  - Infections are a major cause of morbidity and mortality in kidney transplant
      recipients. To some extent, these may be preventable. Careful pretransplant
      screening, immunization, and post-transplant prophylactic antimicrobials may all
      reduce the risk for post-transplant infection. However, because transplant
      recipients may not manifest typical signs and symptoms of infection, diagnoses
      may be confounded. Furthermore, treatment regimens may be complicated by drug
      interactions and the need to maintain immunosuppression to avoid allograft
      rejection. This article reviews common post-transplant infections, including
      prophylactic, diagnostic, and treatment strategies, providing guidance regarding
      care of kidney transplant patients with infection.

PMID- 22977216
TI  - Habitual physical activity measured by accelerometer and survival in maintenance
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: The association between mortality and physical
      activity based on self-report questionnaire in hemodialysis patients has been
      reported previously. However, because self-report is a subjective assessment,
      evaluating true physical activity is difficult. This study investigated the
      prognostic significance of habitual physical activity on 7-year survival in a
      cohort of clinically stable and adequately dialyzed patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A total of 202 Japanese outpatients who were
      undergoing maintenance hemodialysis three times per week at the hemodialysis
      center of Sagami Junkanki Clinic (Japan) from October 2002 to February 2012 were
      followed for up to 7 years. Physical activity was evaluated using an
      accelerometer at study entry and is expressed as the amount of time a patient
      engaged in physical activity on nondialysis days. Cox proportional hazard
      regression was used to assess the contribution of habitual physical activity to
      all-cause mortality. RESULTS: The median patient age was 64 (25th, 75th
      percentiles, 57, 72) years, 52.0% of the patients were women, and the median time
      on hemodialysis was 40.0 (25th, 75th percentiles, 16.8, 119.3) months at
      baseline. During a median follow-up of 45 months, 34 patients died. On
      multivariable analysis, the hazard ratio for all-cause mortality per 10 min/d
      increase in physical activity was 0.78 (95% confidence interval, 0.66-0.92;
      P=0.002). CONCLUSIONS: Engaging in habitual physical activity among outpatients
      undergoing maintenance hemodialysis was associated with decreased mortality risk.

PMID- 22977218
TI  - In data we trust: the role and utility of dialysis provider databases in the
      policy process.

PMID- 22977219
TI  - Initiating and completing the kidney transplant evaluation process: the Red
      Queen's race.

PMID- 22977221
TI  - Construct validation of the Greek version of the Children's Assessment of
      Participation and Enjoyment (CAPE) and Preferences for Activities of Children
      (PAC).
AB  - BACKGROUND: The Children's Assessment of Participation and Enjoyment (CAPE) and
      the Preferences for Activities of Children (PAC) are 2 measures of children's
      participation in various activities. The purpose of this study was the validation
      of the Greek version of "CAPE & PAC." METHODS: The questionnaires were translated
      and pilot tested on a sample of 25 individuals. The reliability and validity of
      the questionnaires were tested on 302 individuals (253 typical population, 49
      disabled), 6-21 years of age. The construct validity of the instruments was
      examined the directional hypothesis by comparing known groups with existing
      differences. An exploratory factor analysis was conducted to determine the
      validity of the typology of activities. The reliability was examined by checking
      the internal consistency of the instruments. RESULTS: The comparison between
      divergent groups confirmed the predicted differences of the mean scores and the
      validity of the instruments. Seven factors (categories of activities) emerged
      from the factor analysis. The acceptable range of Cronbach alpha for the PAC
      scale indicated high consistency. CONCLUSION: This study provides evidence that
      partially support the validity and reliability of "CAPE & PAC" instruments to use
      in Greek population. Further investigation is recommended for both clinical and
      research purposes.

PMID- 22977220
TI  - Association of postoperative proteinuria with AKI after cardiac surgery among
      patients at high risk.
AB  - BACKGROUND AND OBJECTIVES: Preoperative proteinuria is associated with a higher
      incidence of postoperative AKI. Whether the same is true for postoperative
      proteinuria is uncertain. This study tested the hypothesis that increased
      proteinuria after cardiac surgery is associated with an increased risk for AKI.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective cohort study
      included 1198 adults undergoing cardiac surgery at six hospitals between July
      2007 and December 2009. Albuminuria, urine albumin-to-creatinine ratio (ACR), and
      dipstick proteinuria were measured 0-6 hours after surgery. The primary outcome
      was AKI, defined as a doubling in serum creatinine or receipt of acute dialysis
      during the hospital stay. Analyses were adjusted for patient characteristics,
      including preoperative albuminuria. RESULTS: Compared with the lowest quintile,
      the highest quintile of albuminuria and highest grouping of dipstick proteinuria
      were associated with greatest risk for AKI (adjusted relative risks [RRs], 2.97
      [95% confidence interval (CI), 1.20-6.91] and 2.46 [95% CI, 1.16-4.97],
      respectively). Higher ACR was not associated with AKI risk (highest quintile RR,
      1.66 [95% CI, 0.68-3.90]). Of the three proteinuria measures, early postoperative
      albuminuria improved the prediction of AKI to the greatest degree (clinical model
      area under the curve, 0.75; 0.81 with albuminuria). Similar improvements with
      albuminuria were seen for net reclassification index (0.55; P<0.001) and
      integrated discrimination index (0.036; P<0.001). CONCLUSIONS: Higher levels of
      proteinuria after cardiac surgery identify patients at increased risk for AKI
      during their hospital stay.

PMID- 22977222
TI  - A mouse model to study the link between hypoxia, long QT interval and sudden
      infant death syndrome.
AB  - The pathology of sudden infant death syndrome (SIDS) is poorly understood. Many
      risk factors, including hypoxia, have been identified. Prolongation of the ECG
      QTc interval is associated with elevated risk of SIDS but its aetiology in most
      cases remains unknown. We have characterised ECG changes in the newborn mouse in
      the hours and days following birth. There was a steady increase in heart rate
      alongside significant decreases in QTc interval, QRS duration and QTc dispersion
      over the first 10 postnatal days. Birth into hypoxia (10% FiO2) prevented
      electrocardiac maturation, downregulated cardiac ion-channel expression and led
      to neonatal death. We found that risk of death decreased with increasing age of
      exposure to hypoxia. Genetic elevation of cardiac hypoxia-signalling after birth
      in alphaMHC-Cre::VHL(fl/fl) mice also prevented electrocardiographic maturation,
      leading to arrhythmia and death before weaning. Immunohistochemistry and western
      blotting revealed internalisation and dephosphorylation of Connexin43. We
      conclude that increased ambient oxygen concentration after birth drives
      maturation of the cardiac electrical conduction system, failure of which leads to
      aberrant ion channel and Connexin43 expression and predisposes to arrhythmia and
      sudden death. This is consistent with known risk factors of SIDS and provides a
      link between neonatal hypoxia, ECG abnormalities and sudden death.

PMID- 22977223
TI  - Pelvic floor muscle training may improve prolapse stage, muscle function and
      urinary symptoms compared to no training.

PMID- 22977224
TI  - Cardiovascular mortality in relation to birth weight of children and
      grandchildren in 500,000 Norwegian families.
AB  - AIMS: Cardiovascular diseases (CVDs) have been related to low birth weight,
      suggesting the foetal environment may program future risk. Alternatively, common
      genetic factors for both low birth weight and CVD could explain such
      associations. We investigated associations between offspring birth weight and
      paternal and maternal cardiovascular mortality and offspring birth weight and
      cardiovascular mortality among all four grandparents, and further assessed the
      mediating role of maternal smoking during pregnancy. METHODS AND RESULTS: All
      births from 1967 to 2008 that could be linked to parents and grandparents
      comprised the population (n = 1,004,255). The mortality follow-up among parents
      was from 1970 to 2008 and among grandparents from 1960 to 2008. The association
      of grandparental mortality with maternal smoking during pregnancy was analysed in
      a subpopulation of those born after 1997 (n = 345,624). Per quintile higher in
      birth weight was related to 0.82 (0.75-0.89) hazard ratio from coronary heart
      disease in mothers and 0.94 (0.92-0.97) in fathers. For stroke, these were 0.85
      (0.78-0.92) and 0.94 (0.89-1.00), respectively. In grandparents for
      cardiovascular causes, the effects were 0.95 (0.93-0.96) (maternal grandmother),
      0.97 (0.96-0.98) (maternal grandfather), 0.96 (0.94-0.98) (paternal grandmother),
      and 0.98 (0.98-1.00) (paternal grandfather). Adjusting for maternal smoking in
      pregnancy in the subpopulation accounted for much of the effect on grandparental
      cardiovascular mortality in all categories of birth weight. For grandparental
      diabetes mortality, U-shaped associations were seen with grandchild birth weight
      for the maternal grandmother and inverse associations for all other grandparents.
      CONCLUSION: Associations between CVD mortality in all four grandparents and
      grandchild birth weight exist, and while genetic and environmental factors may
      contribute to these, it appears that there is an important role for maternal
      smoking during pregnancy (and associated paternal smoking) in generating these
      associations. For diabetes, however, it appears that intrauterine environmental
      influences and genetic factors contribute to the transgenerational associations.

PMID- 22977226
TI  - Moving from impact to influence: measurement and the changing role of medical
      journals.

PMID- 22977225
TI  - The impact of height on the risk of atrial fibrillation: the Cardiovascular
      Health Study.
AB  - AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased
      body size has been associated with AF, but the relationship is not well
      understood. In this study, we examined the effect of increased height on the risk
      of AF and explore potential mediators and implications for clinical practice.
      METHODS AND RESULTS: We examined data from 5860 individuals taking part in the
      Cardiovascular Health Study, a cohort study of older US adults followed for a
      median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age
      stratified Cox proportional hazards and risk models were used, with focus on the
      effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568
      (27.1%) incident cases in women and men, respectively, greater height was
      significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32,
      confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11
      1.44, P < 0.0001]. The association was such that the incremental risk from sex
      was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32
      1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion
      of height in the Framingham model for incident AF improved discrimination. In
      sequential models, however, we found minimal attenuation of the risk estimates
      for AF with adjustment for left ventricular (LV) mass and left atrial (LA)
      dimension. The associations of LA and LV size measurements with AF risk were
      weakened when indexed to height. CONCLUSION: Independent from sex, increased
      height is significantly associated with the risk of AF.

PMID- 22977227
TI  - Influence of common genetic variation on blood lipid levels, cardiovascular risk,
      and coronary events in two British prospective cohort studies.
AB  - AIMS: The aim of this study was to quantify the collective effect of common lipid
      associated single nucleotide polymorphisms (SNPs) on blood lipid levels,
      cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart
      disease (CHD) events. METHODS AND RESULTS: Analysis was performed in two
      prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women's Heart
      and Health Study (BWHHS; N = 3414). For each participant, scores were calculated
      based on the cumulative effect of multiple genetic variants influencing total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom
      quintile, individuals in the top quintile of the LDL-C genetic score distribution
      had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76
      0.94] and 0.63 [95% CI = 0.50-0.76] mmol/l in WHII and BWHHS, respectively}. They
      also tended to have greater odds of having 'high-risk' status (Framingham 10-year
      cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93-1.98),
      BWHHS: OR = 1.49 (1.14-1.94)]; receiving lipid-lowering treatment [WHII: OR =
      2.38 (1.57-3.59), BWHHS: OR = 2.24 (1.52-3.29)]; and CHD events [WHII: OR = 1.43
      (1.02-2.00), BWHHS: OR = 1.31 (0.99-1.72)]. Similar associations were observed
      for the TC score in both studies. The TG score was associated with high-risk
      status and medication use in both studies. Neither HDL nor TG scores were
      associated with the risk of coronary events. The genetic scores did not improve
      discrimination over the Framingham risk score. CONCLUSION: At the population
      level, common SNPs associated with LDL-C and TC contribute to blood lipid
      variation, cardiovascular risk, use of lipid-lowering medications and coronary
      events. However, their effects are too small to discriminate future lipid
      lowering medication requirements or coronary events.

PMID- 22977228
TI  - What is most important in improving outcomes after pulmonary lobectomy: the
      surgeon or the approach?

PMID- 22977229
TI  - Reply to Neviere et al.

PMID- 22977230
TI  - Human Tribbles 3 protects nuclear DNA from cytidine deamination by APOBEC3A.
AB  - The human polydeoxynucleotide cytidine deaminases APOBEC3A, APOBEC3C, and
      APOBEC3H are capable of mutating viral DNA in the nucleus, whereas APOBEC3A alone
      efficiently edits nuclear DNA. Deamination is rapidly followed by excision of
      uracil residues and can lead to double-stranded breaks. It is not known to which
      protein networks these DNA mutators belong. Using a yeast two-hybrid screen, we
      identified the human homolog of Drosophila Tribbles 3, TRIB3, as an interactor
      for APOBEC3A and APOBEC3C. The interaction was confirmed by co-affinity
      purification. Co-transfection of APOBEC3A with a TRIB3 expression vector reduced
      nuclear DNA editing whereas siRNA knockdown of TRIB3 increased the levels of
      nuclear DNA editing, indicating that TRIB3 functioned as a repressor of A3A. It
      also repressed A3A-associated gammaH2AX positive double-stranded breaks. The
      interaction results in degradation of A3A in a proteasome-independent manner.
      TRIB3 has been linked to cancer and via its own interactors and links the A3A DNA
      mutators to the Rb-BRCA1-ATM network. TRIB3 emerges as an important guardian of
      genome integrity.

PMID- 22977231
TI  - Translesion synthesis across 1,N6-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'
      deoxyadenosine (1,N6-gamma-HMHP-dA) adducts by human and archebacterial DNA
      polymerases.
AB  - The 1,N(6)-(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (1,N(6)
      gamma-HMHP-dA) adducts are formed upon bifunctional alkylation of adenine
      nucleobases in DNA by 1,2,3,4-diepoxybutane, the putative ultimate carcinogenic
      metabolite of 1,3-butadiene. The presence of a substituted 1,N(6)-propano group
      on 1,N(6)-gamma-HMHP-dA is expected to block the Watson-Crick base pairing of the
      adducted adenine with thymine, potentially contributing to mutagenesis. In this
      study, the enzymology of replication past site-specific 1,N(6)-gamma-HMHP-dA
      lesions in the presence of human DNA polymerases (hpols) beta, eta, kappa, and
      iota and archebacterial polymerase Dpo4 was investigated. Run-on gel analysis
      with all four dNTPs revealed that hpol eta, kappa, and Dpo4 were able to copy the
      modified template. In contrast, hpol iota inserted a single base opposite 1,N(6)
      gamma-HMHP-dA but was unable to extend beyond the damaged site, and a complete
      replication block was observed with hpol beta. Single nucleotide incorporation
      experiments indicated that although hpol eta, kappa, and Dpo4 incorporated the
      correct nucleotide (dTMP) opposite the lesion, dGMP and dAMP were inserted with a
      comparable frequency. HPLC-ESI-MS/MS analysis of primer extension products
      confirmed the ability of bypass polymerases to insert dTMP, dAMP, or dGMP
      opposite 1,N(6)-gamma-HMHP-dA and detected large amounts of -1 and -2 deletion
      products. Taken together, these results indicate that hpol eta and kappa enzymes
      bypass 1,N(6)-gamma-HMHP-dA lesions in an error-prone fashion, potentially
      contributing to A->T and A->C transversions and frameshift mutations observed in
      cells following treatment with 1,2,3,4-diepoxybutane.

PMID- 22977232
TI  - Conformational transitions underlying pore opening and desensitization in
      membrane-embedded Gloeobacter violaceus ligand-gated ion channel (GLIC).
AB  - Direct structural insight into the mechanisms underlying activation and
      desensitization remain unavailable for the pentameric ligand-gated channel
      family. Here, we report the structural rearrangements underlying gating
      transitions in membrane-embedded GLIC, a prokaryotic homologue, using site
      directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. We
      particularly probed the conformation of pore-lining second transmembrane segment
      (M2) under conditions that favor the closed and the ligand-bound desensitized
      states. The spin label mobility, intersubunit spin-spin proximity, and the
      solvent-accessibility parameters in the two states clearly delineate the
      underlying protein motions within M2. Our results show that during activation the
      extracellular hydrophobic region undergoes major changes involving an outward
      translational movement, away from the pore axis, leading to an increase in the
      pore diameter, whereas the lower end of M2 remains relatively immobile. Most
      notably, during desensitization, the intervening polar residues in the middle of
      M2 move closer to form a solvent-occluded barrier and thereby reveal the location
      of a distinct desensitization gate. In comparison with the crystal structure of
      GLIC, the structural dynamics of the channel in a membrane environment suggest a
      more loosely packed conformation with water-accessible intrasubunit vestibules
      penetrating from the extracellular end all the way to the middle of M2 in the
      closed state. These regions have been implicated to play a major role in alcohol
      and drug modulation. Overall, these findings represent a key step toward
      understanding the fundamentals of gating mechanisms in this class of channels.

PMID- 22977233
TI  - Structure, sulfatide binding properties, and inhibition of platelet aggregation
      by a disabled-2 protein-derived peptide.
AB  - Disabled-2 (Dab2) targets membranes and triggers a wide range of biological
      events, including endocytosis and platelet aggregation. Dab2, through its
      phosphotyrosine-binding (PTB) domain, inhibits platelet aggregation by competing
      with fibrinogen for alpha(IIb)beta(3) integrin receptor binding. We have recently
      shown that the N-terminal region, including the PTB domain (N-PTB), drives Dab2
      to the platelet membrane surface by binding to sulfatides through two sulfatide
      binding motifs, modulating the extent of platelet aggregation. The three
      dimensional structure of a Dab2-derived peptide encompassing the sulfatide
      binding motifs has been determined in dodecylphosphocholine micelles using NMR
      spectroscopy. Dab2 sulfatide-binding motif contains two helices when embedded in
      micelles, reversibly binds to sulfatides with moderate affinity, lies parallel to
      the micelle surface, and when added to a platelet mixture, reduces the number and
      size of sulfatide-induced aggregates. Overall, our findings identify and
      structurally characterize a minimal region in Dab2 that modulates platelet
      homotypic interactions, all of which provide the foundation for rational design
      of a new generation of anti-aggregatory low-molecular mass molecules for
      therapeutic purposes.

PMID- 22977234
TI  - Role of nuclear receptor coactivator 3 (Ncoa3) in pluripotency maintenance.
AB  - Nuclear receptors, including Esrrb, Dax1, and Nr5a2, have been shown to be
      involved in pluripotency maintenance. Yet, the role of their coactivators in
      mouse embryonic stem cells remains unexplored. Here, we demonstrated that the
      nuclear receptor coactivator 3 (Ncoa3) is essential for pluripotency maintenance.
      Knockdown of Ncoa3 not only compromises the expression of pluripotency markers
      but also impairs in vitro and in vivo differentiation potential of mouse ESCs.
      Ncoa3 binds to the Nanog promoter and recruits the histone acetyltransferase CREB
      binding protein (CBP) and the histone arginine methyltransferase CARM1 to
      activate Nanog expression. Moreover, glycogen synthase kinase 3 GSK3 signaling
      down-regulates the Ncoa3 protein level to suppress Nanog expression. Thus, Ncoa3
      not only contributes to self-renewal by activating Nanog but also facilitates ESC
      differentiation as a break point to disrupt the core transcriptional circuitry of
      pluripotency.

PMID- 22977235
TI  - SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron
      specific manner.
AB  - STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and oxidative
      stress-related kinase (OSR1) activate the potassium-dependent sodium-chloride co
      transporter, NKCC2, and thiazide-sensitive sodium-chloride cotransporter, NCC, in
      vitro, and both co-localize with a kinase regulatory molecule, Cab39/MO25alpha,
      at the apical membrane of the thick ascending limb (TAL) and distal convoluted
      tubule (DCT). Yet genetic ablation of SPAK in mice causes a selective loss of NCC
      function, whereas NKCC2 becomes hyperphosphorylated. Here, we explore the
      underlying mechanisms in wild-type and SPAK-null mice. Unlike in the DCT, OSR1
      remains at the TAL apical membrane of KO mice where it is accompanied by an
      increase in the active, phosphorylated form of AMP-activated kinase. We found an
      alterative SPAK isoform (putative SPAK2 form), which modestly inhibits co
      transporter activity in vitro, is more abundant in the medulla than the cortex.
      Thus, enhanced NKCC2 phosphorylation in the SPAK knock-out may be explained by
      removal of inhibitory SPAK2, sustained activity of OSR1, and activation of other
      kinases. By contrast, the OSR1/SPAK/M025alpha signaling apparatus is disrupted in
      the DCT. OSR1 becomes largely inactive and displaced from M025alpha and NCC at
      the apical membrane, and redistributes to dense punctate structures, containing
      WNK1, within the cytoplasm. These changes are paralleled by a decrease in NCC
      phosphorylation and a decrease in the mass of the distal convoluted tubule,
      exclusive to DCT1. As a result of the dependent nature of OSR1 on SPAK in the
      DCT, NCC is unable to be activated. Consequently, SPAK(-/-) mice are highly
      sensitive to dietary salt restriction, displaying prolonged negative sodium
      balance and hypotension.

PMID- 22977236
TI  - Avirulence protein 3a (AVR3a) from the potato pathogen Phytophthora infestans
      forms homodimers through its predicted translocation region and does not
      specifically bind phospholipids.
AB  - The mechanism of translocation of RxLR effectors from plant pathogenic oomycetes
      into the cytoplasm of their host is currently the object of intense research
      activity and debate. Here, we report the biochemical and thermodynamic
      characterization of the Phytophthora infestans effector AVR3a in vitro. We show
      that the amino acids surrounding the RxLR leader mediate homodimerization of the
      protein. Dimerization was considerably attenuated by a localized mutation within
      the RxLR motif that was previously described to prevent translocation of the
      protein into host. Importantly, we confirm that the reported phospholipid-binding
      properties of AVR3a are mediated by its C-terminal effector domain, not its RxLR
      leader. However, we show that the observed phospholipid interaction is
      attributable to a weak association with denatured protein molecules and is
      therefore most likely physiologically irrelevant.

PMID- 22977237
TI  - Structure of the bone morphogenetic protein receptor ALK2 and implications for
      fibrodysplasia ossificans progressiva.
AB  - Bone morphogenetic protein (BMP) receptor kinases are tightly regulated to
      control development and tissue homeostasis. Mutant receptor kinase domains escape
      regulation leading to severely degenerative diseases and represent an important
      therapeutic target. Fibrodysplasia ossificans progressiva (FOP) is a rare but
      devastating disorder of extraskeletal bone formation. FOP-associated mutations in
      the BMP receptor ALK2 reduce binding of the inhibitor FKBP12 and promote leaky
      signaling in the absence of ligand. To establish structural mechanisms of
      receptor regulation and to address the effects of FOP mutation, we determined the
      crystal structure of the cytoplasmic domain of ALK2 in complex with the
      inhibitors FKBP12 and dorsomorphin. FOP mutations break critical interactions
      that stabilize the inactive state of the kinase, thereby facilitating structural
      rearrangements that diminish FKBP12 binding and promote the correct positioning
      of the glycine-serine-rich loop and alphaC helix for kinase activation. The
      balance of these effects accounts for the comparable activity of R206H and L196P.
      Kinase activation in the clinically benign mutant L196P is far weaker than R206H
      but yields equivalent signals due to the stronger interaction of FKBP12 with
      R206H. The presented ALK2 structure offers a valuable template for the further
      design of specific inhibitors of BMP signaling.

PMID- 22977238
TI  - Dynamin2, clathrin, and lipid rafts mediate endocytosis of the apical Na/K/2Cl
      cotransporter NKCC2 in thick ascending limbs.
AB  - Steady-state surface levels of the apical Na/K/2Cl cotransporter NKCC2 regulate
      NaCl reabsorption by epithelial cells of the renal thick ascending limb (THAL).
      We reported that constitutive endocytosis of NKCC2 controls NaCl absorption in
      native THALs; however, the pathways involved in NKCC2 endocytosis are unknown. We
      hypothesized that NKCC2 endocytosis at the apical surface depends on dynamin-2
      and clathrin. Measurements of steady-state surface NKCC2 and the rate of NKCC2
      endocytosis in freshly isolated rat THALs showed that inhibition of endogenous
      dynamin-2 with dynasore blunted NKCC2 endocytosis by 56 +/- 11% and increased
      steady-state surface NKCC2 by 67 +/- 27% (p < 0.05). Expression of the dominant
      negative Dyn2K44A in THALs slowed the rate of NKCC2 endocytosis by 38 +/- 8% and
      increased steady-state surface NKCC2 by 37 +/- 8%, without changing total NKCC2
      expression. Inhibition of clathrin-mediated endocytosis with chlorpromazine
      blunted NKCC2 endocytosis by 54 +/- 6%, while preventing clathrin from
      interacting with synaptojanin also blunted NKCC2 endocytosis by 52 +/- 5%.
      Disruption of lipid rafts blunted NKCC2 endocytosis by 39 +/- 4% and silencing
      caveolin-1 by 29 +/- 4%. Simultaneous inhibition of clathrin- and lipid raft
      mediated endocytosis completely blocked NKCC2 internalization. We concluded that
      dynamin-2, clathrin, and lipid rafts mediate NKCC2 endocytosis and maintain
      steady-state apical surface NKCC2 in native THALs. These are the first data
      identifying the endocytic pathway for apical NKCC2 endocytosis.

PMID- 22977239
TI  - Properties of a novel PBP2A protein homolog from Staphylococcus aureus strain
      LGA251 and its contribution to the beta-lactam-resistant phenotype.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains show strain-to-strain
      variation in resistance level, in genetic background, and also in the structure
      of the chromosomal cassette (SCCmec) that carries the resistance gene mecA. In
      contrast, strain-to-strain variation in the sequence of the mecA determinant was
      found to be much more limited among MRSA isolates examined so far. The first
      exception to this came with the recent identification of MRSA strain LGA251,
      which carries a new homolog of this gene together with regulatory elements
      mecI/mecR that also have novel, highly divergent structures. After cloning and
      purification in Escherichia coli, PBP2A(LGA), the protein product of the new mecA
      homolog, showed aberrant mobility in SDS-PAGE, structural instability and loss of
      activity at 37  degrees C, and a higher relative affinity for oxacillin as
      compared with cefoxitin. The mecA homolog free of its regulatory elements was
      cloned into a plasmid and introduced into the background of the beta-lactam
      susceptible S. aureus strain COL-S. In this background, the mecA homolog
      expressed a high-level resistance to cefoxitin (MIC = 400 MUg/ml) and a somewhat
      lower resistance to oxacillin (minimal inhibitory concentration = 200 MUg/ml).
      Similar to PBP2A, the protein homolog PBP2A(LGA) was able to replace the
      essential function of the S. aureus PBP2 for growth. In contrast to PBP2A,
      PBP2A(LGA) did not depend on the transglycosylase activity of the native PBP2 for
      expression of high level resistance to oxacillin, suggesting that the PBP2A
      homolog may preferentially cooperate with a monofunctional transglycosylase as
      the alternative source of transglycosylase activity.

PMID- 22977240
TI  - The functional properties of human slow skeletal troponin T isoforms in cardiac
      muscle regulation.
AB  - Human slow skeletal troponin T (HSSTnT) shares a high degree of homology with
      cardiac TnT (CTnT). Although the presence of HSSTnT has not been confirmed in the
      heart at the protein level, detectable levels of HSSTnT mRNA have been found.
      Whether HSSTnT isoforms are expressed transiently remains unknown. Because
      transient re-expression of HSSTnT may be a potential mechanism of regulating
      function, we explored the effect of HSSTnT on the regulation of cardiac muscle.
      At least three HSSTnT isoforms have been found to exist in slow skeletal muscle:
      HSSTnT1 (+exons 5 and 12), HSSTnT2 (+exon 5, -exon 12), and HSSTnT3 (-exons 5 and
      12). Another isoform, HSSTnT hypothetical (Hyp) (-exon 5, +exon 12), has only
      been found at the mRNA level. Compared with HCTnT3 (adult isoform), Tn complexes
      containing HSSTnT1, -2, and -3 did not alter the actomyosin ATPase activation and
      inhibition in the presence and absence of Ca(2+), respectively. HSSTnTHyp was not
      evaluated as it did not form a Tn complex under a variety of conditions. Porcine
      papillary skinned fibers displaced with HSSTnT1, -2, or -3 and reconstituted with
      human cardiac troponin I and troponin C (HCTnI.TnC) complex showed a decrease in
      the Ca(2+) sensitivity of force development and an increase in maximal recovered
      force (HSSTnT1 and -3) compared with HCTnT3. In contrast, HSSTnTHyp showed an
      increase in the Ca(2+) sensitivity of force development. This suggests that re-
      or overexpression of specific SSTnT isoforms might have therapeutic potential in
      the failing heart because they increase the maximal force of contraction. In
      addition, circular dichroism and proteolytic digestion experiments revealed
      structural differences between HSSTnT isoforms and HCTnT3 and that HSSTnT1 is
      more susceptible to calpain and trypsin proteolysis than the other HSSTnTs.
      Overall, HSSTnT isoforms despite being homologues of CTnT may display distinct
      functional properties in muscle regulation.

PMID- 22977241
TI  - The ATPase pathway that drives the kinesin-14 Kar3Vik1 powerstroke.
AB  - Kar3, a Saccharomyces cerevisiae microtubule minus-end-directed kinesin-14,
      dimerizes with either Vik1 or Cik1. The C-terminal globular domain of Vik1
      exhibits the structure of a kinesin motor domain and binds microtubules
      independently of Kar3 but lacks a nucleotide binding site. The only known
      function of Kar3Vik1 is to cross-link parallel microtubules at the spindle poles
      during mitosis. In contrast, Kar3Cik1 depolymerizes microtubules during mating
      but cross-links antiparallel microtubules in the spindle overlap zone during
      mitosis. A recent study showed that Kar3Vik1 binds across adjacent microtubule
      protofilaments and uses a minus-end-directed powerstroke to drive ATP-dependent
      motility. The presteady-state experiments presented here extend this study and
      establish an ATPase model for the powerstroke mechanism. The results incorporated
      into the model indicate that Kar3Vik1 collides with the microtubule at 2.4 MUm(
      1) s(-1) through Vik1, promoting microtubule binding by Kar3 followed by ADP
      release at 14 s(-1). The tight binding of Kar3 to the microtubule destabilizes
      the Vik1 interaction with the microtubule, positioning Kar3Vik1 for the start of
      the powerstroke. Rapid ATP binding to Kar3 is associated with rotation of the
      coiled-coil stalk, and the postpowerstroke ATP hydrolysis at 26 s(-1) is
      independent of Vik1, providing further evidence that Vik1 rotates with the coiled
      coil during the powerstroke. Detachment of Kar3Vik1 from the microtubule at 6 s(
      1) completes the cycle and allows the motor to return to its initial
      conformation. The results also reveal key differences in the ATPase cycles of
      Kar3Vik1 and Kar3Cik1, supporting the fact that these two motors have distinctive
      biological functions.

PMID- 22977242
TI  - Allosteric communication between the pyridoxal 5'-phosphate (PLP) and heme sites
      in the H2S generator human cystathionine beta-synthase.
AB  - Human cystathionine beta-synthase (CBS) is a unique pyridoxal 5'-phosphate (PLP)
      dependent enzyme that has a regulatory heme cofactor. Previous studies have
      demonstrated the importance of Arg-266, a residue at the heme pocket end of alpha
      helix 8, for communication between the heme and PLP sites. In this study, we have
      examined the role of the conserved Thr-257 and Thr-260 residues, located at the
      other end of alpha-helix 8 on the heme electronic environment and on activity.
      The mutations at the two positions destabilize PLP binding, leading to lower PLP
      content and ~2- to ~500-fold lower activity compared with the wild-type enzyme.
      Activity is unresponsive to PLP supplementation, consistent with the pyridoxine
      nonresponsive phenotype of the T257M mutation in a homocystinuric patient. The
      H(2)S-producing activities, also impacted by the mutations, show a different
      pattern of inhibition compared with the canonical transsulfuration reaction.
      Interestingly, the mutants exhibit contrasting sensitivities to the allosteric
      effector, S-adenosylmethionine (AdoMet); whereas T257M and T257I are inhibited,
      the other mutants are hyperactivated by AdoMet. All mutants showed an increased
      propensity of the ferrous heme to form an inactive species with a 424 nm Soret
      peak and exhibited significantly reduced enzyme activity in the ferrous and
      ferrous-CO states. Our results provide the first evidence for bidirectional
      transmission of information between the cofactor binding sites, suggest the
      additional involvement of this region in allosteric communication with the
      regulatory AdoMet-binding domain, and reveal the potential for independent
      modulation of the canonical transsulfuration versus H(2)S-generating reactions
      catalyzed by CBS.

PMID- 22977243
TI  - The extracellular protein factor Epf from Streptococcus pyogenes is a cell
      surface adhesin that binds to cells through an N-terminal domain containing a
      carbohydrate-binding module.
AB  - Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment
      to and entry into epithelial cells is a prerequisite for a successful infection
      of the human host and requires adhesins. Here, we demonstrate that the
      multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin.
      An epf-deficient mutant showed significantly decreased adhesion to and
      internalization into human keratinocytes. Cell adhesion is mediated by the N
      terminal domain of Epf (EpfN) and increased by the human plasma protein
      plasminogen. The crystal structure of EpfN, solved at 1.6 A resolution, shows
      that it consists of two subdomains: a carbohydrate-binding module and a
      fibronectin type III domain. Both fold types commonly participate in ligand
      receptor and protein-protein interactions. EpfN is followed by 18 repeats of a
      domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal
      cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but
      biophysical studies show they are predominantly alpha-helical and form a fiber
      like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread
      family of adhesins known as MSCRAMMs (microbial surface components recognizing
      adhesive matrix molecules), in which a cell wall-attached stalk enables long
      range interactions via its adhesive N-terminal domain.

PMID- 22977244
TI  - Phosphatidylinositol 4-kinases are required for autophagic membrane trafficking.
AB  - Macroautophagy (hereafter autophagy) is a degradative cellular pathway that
      protects eukaryotic cells from stress, starvation, and microbial infection. This
      process must be tightly controlled because too little or too much autophagy can
      be deleterious to cellular physiology. The phosphatidylinositol (PtdIns) 3-kinase
      Vps34 is a lipid kinase that regulates autophagy, but the role of other PtdIns
      kinases has not been examined. Here we demonstrate a role for PtdIns 4-kinases
      and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast.
      The PtdIns 4-kinase Pik1 is involved in Atg9 trafficking through the Golgi and is
      involved in both nonselective and selective types of autophagy, whereas the
      PtdIns4P 5-kinase Mss4 is specifically involved in mitophagy but not nonselective
      autophagy. Our data indicate that phosphoinositide kinases have multiple roles in
      the regulation of autophagic pathways.

PMID- 22977245
TI  - Two related RNA-editing proteins target the same sites in mitochondria of
      Arabidopsis thaliana.
AB  - The facilitators for specific cytosine-to-uridine RNA-editing events in plant
      mitochondria and plastids are pentatricopeptide repeat (PPR)-containing proteins
      with specific additional C-terminal domains. Here we report the related PPR
      proteins mitochondrial editing factor 8 (MEF8) and MEF8S with only five such
      repeats each to be both involved in RNA editing at the same two sites in
      mitochondria of Arabidopsis thaliana. Mutants of MEF8 show diminished editing in
      leaves but not in pollen, whereas mutants of the related protein MEF8S show
      reduced RNA editing in pollen but not in leaves. Overexpressed MEF8 or MEF8S both
      increase editing at the two target sites in a mef8 mutant. Double mutants of MEF8
      and MEF8S are not viable although both identified target sites are in mRNAs for
      nonessential proteins. This suggests that MEF8 and MEF8S may have other essential
      functions beyond these two editing sites in complex I mRNAs.

PMID- 22977246
TI  - An interaction between DNA polymerase and helicase is essential for the high
      processivity of the bacteriophage T7 replisome.
AB  - Synthesis of the leading DNA strand requires the coordinated activity of DNA
      polymerase and DNA helicase, whereas synthesis of the lagging strand involves
      interactions of these proteins with DNA primase. We present the first structural
      model of a bacteriophage T7 DNA helicase-DNA polymerase complex using a
      combination of small angle x-ray scattering, single-molecule, and biochemical
      methods. We propose that the protein-protein interface stabilizing the leading
      strand synthesis involves two distinct interactions: a stable binding of the
      helicase to the palm domain of the polymerase and an electrostatic binding of the
      carboxyl-terminal tail of the helicase to a basic patch on the polymerase. DNA
      primase facilitates binding of DNA helicase to ssDNA and contributes to formation
      of the DNA helicase-DNA polymerase complex by stabilizing DNA helicase.

PMID- 22977247
TI  - Glutathione and glutaredoxin act as a backup of human thioredoxin reductase 1 to
      reduce thioredoxin 1 preventing cell death by aurothioglucose.
AB  - Thioredoxin reductase 1 (TrxR1) in cytosol is the only known reductant of
      oxidized thioredoxin 1 (Trx1) in vivo so far. We and others found that
      aurothioglucose (ATG), a well known active-site inhibitor of TrxR1, inhibited
      TrxR1 activity in HeLa cell cytosol but had no effect on the viability of the
      cells. Using a redox Western blot analysis, no change was observed in redox state
      of Trx1, which was mainly fully reduced with five sulfhydryl groups. In contrast,
      auranofin killed cells and oxidized Trx1, also targeting mitochondrial TrxR2 and
      Trx2. Combining ATG with ebselen gave a strong synergistic effect, leading to
      Trx1 oxidation, reactive oxygen species accumulation, and cell death. We
      hypothesized that there should exist a backup system to reduce Trx1 when only
      TrxR1 activity was lost. Our results showed that physiological concentrations of
      glutathione, NADPH, and glutathione reductase reduced Trx1 in vitro and that the
      reaction was strongly stimulated by glutaredoxin1. Simultaneous depletion of TrxR
      activity by ATG and glutathione by buthionine sulfoximine led to overoxidation of
      Trx1 and loss of HeLa cell viability. In conclusion, the glutaredoxin system and
      glutathione have a backup role to keep Trx1 reduced in cells with loss of TrxR1
      activity. Monitoring the redox state of Trx1 shows that cell death occurs when
      Trx1 is oxidized, followed by general protein oxidation catalyzed by the
      disulfide form of thioredoxin.

PMID- 22977248
TI  - Nucleotide activation of the Ca-ATPase.
AB  - We have used fluorescence spectroscopy, molecular modeling, and limited
      proteolysis to examine structural dynamics of the sarcoplasmic reticulum Ca
      ATPase (SERCA). The Ca-ATPase in sarcoplasmic reticulum vesicles from fast twitch
      muscle (SERCA1a isoform) was selectively labeled with fluorescein isothiocyanate
      (FITC), a probe that specifically reacts with Lys-515 in the nucleotide-binding
      site. Conformation-specific proteolysis demonstrated that FITC labeling does not
      induce closure of the cytoplasmic headpiece, thereby assigning FITC-SERCA as a
      nucleotide-free enzyme. We used enzyme reverse mode to synthesize FITC
      monophosphate (FMP) on SERCA, producing a phosphorylated pseudosubstrate tethered
      to the nucleotide-binding site of a Ca(2+)-free enzyme (E2 state to prevent FMP
      hydrolysis). Conformation-specific proteolysis demonstrated that FMP formation
      induces SERCA headpiece closure similar to ATP binding, presumably due to the
      high energy phosphoryl group on the fluorescent probe (ATP.E2 analog).
      Subnanosecond-resolved detection of fluorescence lifetime, anisotropy, and
      quenching was used to characterize FMP-SERCA (ATP.E2 state) versus FITC-SERCA in
      Ca(2+)-free, Ca(2+)-bound, and actively cycling phosphoenzyme states (E2, E1, and
      EP). Time-resolved spectroscopy revealed that FMP-SERCA exhibits increased probe
      dynamics but decreased probe accessibility compared with FITC-SERCA, indicating
      that ATP exhibits enhanced dynamics within a closed cytoplasmic headpiece.
      Molecular modeling was used to calculate the solvent-accessible surface area of
      FITC and FMP bound to SERCA crystal structures, revealing a positive correlation
      of solvent-accessible surface area with quenching but not anisotropy. Thus,
      headpiece closure is coupled to substrate binding but not active site dynamics.
      We propose that dynamics in the nucleotide-binding site of SERCA is important for
      Ca(2+) binding (distal allostery) and phosphoenzyme formation (direct
      activation).

PMID- 22977249
TI  - Membrane tethering and nucleotide-dependent conformational changes drive
      mitochondrial genome maintenance (Mgm1) protein-mediated membrane fusion.
AB  - Cellular membrane remodeling events such as mitochondrial dynamics, vesicle
      budding, and cell division rely on the large GTPases of the dynamin superfamily.
      Dynamins have long been characterized as fission molecules; however, how they
      mediate membrane fusion is largely unknown. Here we have characterized by cryo
      electron microscopy and in vitro liposome fusion assays how the mitochondrial
      dynamin Mgm1 may mediate membrane fusion. Using cryo-EM, we first demonstrate
      that the Mgm1 complex is able to tether opposing membranes to a gap of ~15 nm,
      the size of mitochondrial cristae folds. We further show that the Mgm1 oligomer
      undergoes a dramatic GTP-dependent conformational change suggesting that s-Mgm1
      interactions could overcome repelling forces at fusion sites and that
      ultrastructural changes could promote the fusion of opposing membranes. Together
      our findings provide mechanistic details of the two known in vivo functions of
      Mgm1, membrane fusion and cristae maintenance, and more generally shed light onto
      how dynamins may function as fusion proteins.

PMID- 22977250
TI  - Functional and structural characterization of PaeM, a colicin M-like bacteriocin
      produced by Pseudomonas aeruginosa.
AB  - Colicin M (ColM) is the only enzymatic colicin reported to date that inhibits
      cell wall peptidoglycan biosynthesis. It catalyzes the specific degradation of
      the lipid intermediates involved in this pathway, thereby provoking lysis of
      susceptible Escherichia coli cells. A gene encoding a homologue of ColM was
      detected within the exoU-containing genomic island A carried by certain
      pathogenic Pseudomonas aeruginosa strains. This bacteriocin (pyocin) that we have
      named PaeM was crystallized, and its structure with and without an Mg(2+) ion
      bound was solved. In parallel, site-directed mutagenesis of conserved PaeM
      residues from the C-terminal domain was performed, confirming their essentiality
      for the protein activity both in vitro (lipid II-degrading activity) and in vivo
      (cytotoxicity against a susceptible P. aeruginosa strain). Although PaeM is
      structurally similar to ColM, the conformation of their active sites differs
      radically; in PaeM, residues essential for enzymatic activity and cytotoxicity
      converge toward a same pocket, whereas in ColM they are spread along a
      particularly elongated active site. We have also isolated a minimal domain
      corresponding to the C-terminal half of the PaeM protein and exhibiting a 70-fold
      higher enzymatic activity as compared with the full-length protein. This isolated
      domain of the PaeM bacteriocin was further shown to kill E. coli cells when
      addressed to the periplasm of these bacteria.

PMID- 22977251
TI  - Distinct activation properties of the nuclear factor of activated T-cells (NFAT)
      isoforms NFATc3 and NFATc4 in neurons.
AB  - The Ca(2+)/calcineurin-dependent transcription factor NFAT (nuclear factor of
      activated T-cells) is implicated in regulating dendritic and axonal development,
      synaptogenesis, and neuronal survival. Despite the increasing appreciation for
      the importance of NFAT-dependent transcription in the nervous system, the
      regulation and function of specific NFAT isoforms in neurons are poorly
      understood. Here, we compare the activation of NFATc3 and NFATc4 in hippocampal
      and dorsal root ganglion neurons following electrically evoked elevations of
      intracellular Ca(2+) concentration ([Ca(2+)](i)). We find that NFATc3 undergoes
      rapid dephosphorylation and nuclear translocation that are essentially complete
      within 20 min, although NFATc4 remains phosphorylated and localized to the
      cytosol, only exhibiting nuclear localization following prolonged (1-3 h)
      depolarization. Knocking down NFATc3, but not NFATc4, strongly diminished NFAT
      mediated transcription induced by mild depolarization in neurons. By analyzing
      NFATc3/NFATc4 chimeras, we find that the region containing the serine-rich region
      1 (SRR1) mildly affects initial NFAT translocation, although the region
      containing the serine-proline repeats is critical for determining the magnitude
      of NFAT activation and nuclear localization upon depolarization. Knockdown of
      glycogen synthase kinase 3beta (GSK3beta) significantly increased the
      depolarization-induced nuclear localization of NFATc4. In contrast, inhibition of
      p38 or mammalian target of rapamycin (mTOR) kinases had no significant effect on
      nuclear import of NFATc4. Thus, electrically evoked [Ca(2+)](i) elevation in
      neurons rapidly and strongly activates NFATc3, whereas activation of NFATc4
      requires a coincident increase in [Ca(2+)](i) and suppression of GSK3beta, with
      differences in the serine-proline-containing region giving rise to these distinct
      activation properties of NFATc3 and NFATc4.

PMID- 22977252
TI  - Orphan nuclear receptor small heterodimer partner negatively regulates growth
      hormone-mediated induction of hepatic gluconeogenesis through inhibition of
      signal transducer and activator of transcription 5 (STAT5) transactivation.
AB  - Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid
      metabolism. Ataxia telangiectasia mutated (ATM) is a member of the
      phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression.
      The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a
      pivotal role in regulating metabolic processes. Here, we studied the role of ATM
      on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced
      phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene
      expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5
      overexpression in hepatocytes increased glucose production, which was blocked by
      a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We
      identified a STAT5 binding site on the PEPCK gene promoter using reporter assays
      and point mutation analysis. Up-regulation of SHP by metformin-mediated
      activation of the ATM-AMP-activated protein kinase pathway led to inhibition of
      GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM
      inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically
      interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter.
      GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP,
      whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the
      increase of hepatic gluconeogenesis following GH treatment was significantly
      higher in the liver of SHP null mice compared with that of wild-type mice.
      Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP
      network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH
      dependent pathway, may be a potential therapeutic target for insulin resistance.

PMID- 22977253
TI  - Kinetic modeling of human hepatic glucose metabolism in type 2 diabetes mellitus
      predicts higher risk of hypoglycemic events in rigorous insulin therapy.
AB  - A major problem in the insulin therapy of patients with diabetes type 2 (T2DM) is
      the increased occurrence of hypoglycemic events which, if left untreated, may
      cause confusion or fainting and in severe cases seizures, coma, and even death.
      To elucidate the potential contribution of the liver to hypoglycemia in T2DM we
      applied a detailed kinetic model of human hepatic glucose metabolism to simulate
      changes in glycolysis, gluconeogenesis, and glycogen metabolism induced by
      deviations of the hormones insulin, glucagon, and epinephrine from their normal
      plasma profiles. Our simulations reveal in line with experimental and clinical
      data from a multitude of studies in T2DM, (i) significant changes in the relative
      contribution of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic
      glucose production and hepatic glucose utilization; (ii) decreased postprandial
      glycogen storage as well as increased glycogen depletion in overnight fasting and
      short term fasting; and (iii) a shift of the set point defining the switch
      between hepatic glucose production and hepatic glucose utilization to elevated
      plasma glucose levels, respectively, in T2DM relative to normal, healthy
      subjects. Intriguingly, our model simulations predict a restricted gluconeogenic
      response of the liver under impaired hormonal signals observed in T2DM, resulting
      in an increased risk of hypoglycemia. The inability of hepatic glucose metabolism
      to effectively counterbalance a decline of the blood glucose level becomes even
      more pronounced in case of tightly controlled insulin treatment. Given this Janus
      face mode of action of insulin, our model simulations underline the great
      potential that normalization of the plasma glucagon profile may have for the
      treatment of T2DM.

PMID- 22977254
TI  - Dynamin regulates specific membrane fusion events necessary for acrosomal
      exocytosis in mouse spermatozoa.
AB  - Mammalian spermatozoa must complete an acrosome reaction prior to fertilizing an
      oocyte. The acrosome reaction is a unique exocytotic event involving a series of
      prolonged membrane fusions that ultimately result in the production of membrane
      vesicles and release of the acrosomal contents. This event requires the concerted
      action of a large number of fusion-competent signaling and scaffolding proteins.
      Here we show that two different members of the dynamin GTPase family localize to
      the developing acrosome of maturing mouse germ cells. Both dynamin 1 and 2 also
      remain within the periacrosomal region of mature mouse spermatozoa and are thus
      well positioned to regulate the acrosome reaction. Two pharmacological inhibitors
      of dynamin, dynasore and Dyngo-4a, blocked the in vitro induction of acrosomal
      exocytosis by progesterone, but not by the calcium ionophore A23187, and elicited
      a concomitant reduction of in vitro fertilization. In vivo treatment with these
      inhibitors also resulted in spermatozoa displaying reduced acrosome reaction
      potential. Dynamin 1 and 2 phosphorylation increased on progesterone treatment,
      and this was also selectively blocked by dynasore. On the basis of our collective
      data, we propose that dynamin could regulate specific membrane fusion events
      necessary for acrosomal exocytosis in mouse spermatozoa.

PMID- 22977255
TI  - Global identification of new substrates for the yeast endoribonuclease, RNase
      mitochondrial RNA processing (MRP).
AB  - RNase mitochondrial RNA processing (MRP) is an essential, evolutionarily
      conserved endoribonuclease composed of 10 different protein subunits and a single
      RNA. RNase MRP has established roles in multiple pathways including ribosome
      biogenesis, cell cycle regulation, and mitochondrial DNA replication. Although
      each of these functions is important to cell growth, additional functions may
      exist given the essential nature of the complex. To identify novel RNase MRP
      substrates, we utilized RNA immunoprecipitation and microarray chip analysis to
      identify RNA that physically associates with RNase MRP. We identified several new
      potential substrates for RNase MRP including a cell cycle-regulated transcript,
      CTS1; the yeast homolog of the mammalian p27(Kip1), SIC1; and the U2 RNA
      component of the spliceosome. In addition, we found RNase MRP to be involved in
      the regulation of the Ty1 transposon RNA. These results reinforce and broaden the
      role of RNase MRP in cell cycle regulation and help to identify new roles of this
      endoribonuclease.

PMID- 22977256
TI  - Glycodelin-A stimulates interleukin-6 secretion by human monocytes and
      macrophages through L-selectin and the extracellular signal-regulated kinase
      pathway.
AB  - Macrophages represent the second major type of decidual leukocytes at the
      fetomaternal interface. Changes in macrophage number and activity are associated
      with fetal loss and pregnancy complications. Glycodelin-A (GdA) is an abundant
      glycoprotein in the first-trimester decidua. It is involved in fetomaternal
      defense and early placental development through its regulatory activities in
      various immune cells. The N-glycosylation of GdA mediates the binding and
      therefore the activities of the molecule. In this study, we studied the
      biological activities of GdA in the functions of human monocytes/macrophages. GdA
      was purified from amniotic fluid by affinity chromatography. GdA treatment did
      not affect the viability, cell death, or phagocytic activity of the
      monocytes/macrophages. GdA, but not recombinant glycodelin without glycosylation,
      induced IL-6 production as demonstrated by cytokine array, intracellular
      staining, and ELISA. GdA also induced phosphorylation of ERK in
      monocytes/macrophages. The involvement of ERKs in IL-6 induction was confirmed
      using pharmacological inhibitors. Co-immunoprecipitation showed that L-selectin
      on the monocytes/macrophages was the binding protein of GdA. Treatment with anti
      L-selectin antibody reduced GdA binding and GdA-induced IL-6 production. GdA
      treated macrophages suppressed IFN-gamma expression by co-cultured T-helper cells
      in an IL-6-dependent manner. These results show that GdA interacts with L
      selectin to induce IL-6 production in monocytes/macrophages by activating the ERK
      signaling pathway. In turn, the increased IL-6 production suppresses IFN-gamma
      expression in T-helper cells, which may play an important role in inducing a Th-2
      polarized cytokine environment that flavors the immunotolerance of the
      fetoplacental unit.

PMID- 22977257
TI  - Prostaglandin E2-induced IL-23p19 subunit is regulated by cAMP-responsive element
      binding protein and C/AATT enhancer-binding protein beta in bone marrow-derived
      dendritic cells.
AB  - We reported previously that prostaglandin E2 (PGE2) up-regulates IL-23 in vitro
      in bone marrow-derived dendritic cells and in vivo in models of collagen-induced
      arthritis and inflammatory bowel disease, leading to preferential Th17
      development and activity. There is very little information on the molecular
      mechanisms involved in the PGE2-induced up-regulation of Il23a gene expression.
      In this study we investigated the signaling pathways and transcription factors
      involved in the stimulatory effect of PGE2. Although PGE2 does not induce IL
      23p19 expression by itself, it synergizes with both extra- and intracellular Toll
      like receptor ligands and with inflammatory cytokines such as TNFalpha. We
      established that the effect of PGE2 in conjunction with either LPS or TNFalpha is
      mediated through the EP4 receptor and the cAMP-dependent activation of both
      protein kinase A (PKA) and exchange protein activated by cAMP (EPAC). Using the
      EP4 agonist PGE(1)OH in conjunction with TNFalpha, we found that PKA-induced
      phosphorylation of cAMP-response element-binding protein ((P)CREB) and EPAC
      induced phosphorylation of C/AATT enhancer-binding protein beta ((P)C/EBPbeta)
      mediate the stimulatory effect of PGE2 on IL-23p19 expression. This is the first
      report of CREB and C/EBPbeta involvement in Il23a promoter activation. Mutation
      within the putative CREB and C/EBP sites combined with in vivo DNA binding (ChIP)
      assays identified the distal CREB site (-1125) and the two proximal C/EBP sites (
      274 and -232) as essential for PKA-activated CREB and EPAC-activated C/EBPbeta
      induced IL-23p19 expression.

PMID- 22977259
TI  - Delayed cutaneous wound healing in Fam129b/Minerva-deficient mice.
AB  - A recent integrative analysis using a phosphoproteomic approach identified
      FAM129B, also known as MINERVA, as a downstream effector of the MAP kinase
      pathway in human melanoma cells. FAM129B protein, which is a member of a small
      family of proteins, was also found to suppress TNFalpha/cycloheximide-induced
      apoptosis in HeLa cells. To investigate the physiological functions of Fam129b in
      vivo, we generated gene-targeted Fam129b-mutant mice in which, the amino terminal
      coding exon was replaced by lacZ. We found that homozygous mutant mice are viable
      and fertile and that Fam129b is considerably expressed in most of the epidermal
      keratinocytes of both embryonic and adult mice. Although no gross defect was
      observed in the skin of the Fam129b-deficient mice, wound healing subsequent to
      skin puncturing was significantly delayed. Furthermore, overexpression of Fam129b
      promoted HaCaT cell motility in an N-terminal pleckstrin homology domain
      dependent manner, but not proliferation. Microarray analysis of the Fam129b
      transfectant exhibited substantial upregulation of several genes related to wound
      repair and cell motility. These results suggest that expression of Fam129b in
      epidermal keratinocytes accompanied by alteration of wound healing-related gene
      expression is necessary for regulation of cell motility and thereby, contributes
      to the appropriate wound healing process.

PMID- 22977260
TI  - Identifying asymptomatic carotid stenosis patients at high risk of
      cerebrovascular events: the missing piece of the puzzle?

PMID- 22977258
TI  - Distinct expression patterns of glycoprotein hormone subunits in the
      lophotrochozoan Aplysia: implications for the evolution of neuroendocrine systems
      in animals.
AB  - Glycoprotein hormones (GPHs) comprise a group of signaling molecules critical for
      major metabolic and reproductive functions. In vertebrates they include chorionic
      gonadotropin, LH, FSH, and TSH. The active hormones are characterized by
      heterodimerization between a common alpha and hormone-specific beta subunit,
      which activate leucine-rich repeat-containing G protein coupled receptors. To
      date, genes referred to as GPHalpha2 and GPHbeta5 have been the only glycoprotein
      hormone subunits identified in invertebrates, suggesting that other GPHalpha and
      GPHbeta subunits diversified during vertebrate evolution. Still the functions of
      GPHalpha2 and GPHbeta5 remain largely unknown for both vertebrates and
      invertebrates. To further understand the evolution and putative function of these
      subunits, we cloned and analyzed phylogenetically two glycoprotein subunits,
      AcaGPHalpha and AcaGPHbeta, from the sea hare Aplysia californica. Model based
      three-dimensional predictions of AcaGPHbeta confirm the presence of a complete
      cysteine knot, two hairpin loops, and a long loop. As in the human GPHbeta5
      subunit the seatbelt structure is absent in AcaGPHbeta. We also found that
      AcaGPHalpha and AcaGPHbeta subunits are expressed in larval stages of Aplysia,
      and we present a detailed expression map of the subunits in the adult central
      nervous system using in situ hybridizations. Both subunits are expressed in
      subpopulations of pleural and buccal mechanosensory neurons, suggesting a
      neuronal modulatory function of these subunits in Aplysia. Furthermore it
      supports the model of a relatively diffuse neuroendocrine-like system in
      molluscs, where specific primary sensory neurons release peptides
      extrasynaptically (paracrine secretion). This is in contrast to vertebrates and
      insects, in which releasing and stimulating factor from centralized sensory
      regions of the central nervous system ultimately regulate hormone release in
      peripheral glands.

PMID- 22977261
TI  - Mean platelet volume in patients with dilated cardiomyopathy and left ventricular
      thrombus.

PMID- 22977263
TI  - The European Heart Journal and the European Journal of Heart Failure: partners in
      scientific publishing.

PMID- 22977264
TI  - Should antidiabetic treatment of type 2 diabetes in patients with heart failure
      differ from that in patients without?
AB  - AIMS: Patients with type 2 diabetes are at high risk for developing heart
      failure. Evidence-based treatment recommendations with respect to the specific
      benefits or possible hazards of antidiabetic treatment are scarce. METHODS AND
      RESULTS: In a systematic search we only identified randomized, controlled trials
      for thiazolidinediones. Further evidence is largely based on subgroup analyses of
      larger intervention studies in mostly systolic heart failure, on observational
      studies, or on registries. Acknowledging this lack of data, hyperglycaemia should
      be treated to appropriate guideline-recommended targets and hypoglycaemia avoided
      until this evidence becomes available. Thiazolidinediones should not be used
      because of an increased event rate in diabetic patients with established heart
      failure and a large increase in incident heart failure. All other glucose
      lowering strategies might be used in patients with diabetes and heart failure,
      but specific precautions must be considered. CONCLUSIONS: The documented lack of
      data calls for specific trials, as diabetes and heart failure as well as their co
      morbidities are highly prevalent and are becoming even more important with an
      increasing prevalence of obesity and an ageing population.

PMID- 22977265
TI  - A preliminary investigation of stimulus control training for worry: effects on
      anxiety and insomnia.
AB  - For individuals with generalized anxiety disorder, worry becomes associated with
      numerous aspects of life (e.g., time of day, specific stimuli, environmental
      cues) and is thus under poor discriminative stimulus control (SC). In addition,
      excessive worry is associated with anxiety, depressed mood, and sleep
      difficulties. This investigation sought to provide preliminary evidence for the
      efficacy of SC procedures in reducing anxiety-, mood-, and sleep-related
      symptoms. A total of 53 participants with high trait worry were randomly assigned
      to receive 2 weeks of either SC training (consisting of a 30-min time- and place
      restricted worry period each day) or a control condition called focused worry
      (FW; consisting of instructions to not avoid naturally occurring worry so that
      worry and anxiety would not paradoxically increase). At post-training, SC was
      superior to FW in producing reductions on measures of worry, anxiety, negative
      affect, and insomnia, but not on measures of depression or positive affect.
      Moreover, SC was superior to FW in producing clinically significant change on
      measures of worry and anxiety. Results provide preliminary support for the use of
      SC training techniques in larger treatment packages for individuals who
      experience high levels of worry.

PMID- 22977266
TI  - Augmenting visual analysis in single-case research with hierarchical linear
      modeling.
AB  - The purpose of this article is to demonstrate how hierarchical linear modeling
      (HLM) can be used to enhance visual analysis of single-case research (SCR)
      designs. First, the authors demonstrated the use of growth modeling via HLM to
      augment visual analysis of a sophisticated single-case study. Data were used from
      a delayed multiple baseline design, across groups of participants, with an
      embedded changing criterion design in a single-case literacy project for students
      with moderate intellectual disabilities (MoID). Visual analysis revealed a
      functional relation between instruction and sight-word acquisition for all
      students. Growth HLM quantified relations at the group level and revealed
      additional information that included statistically significant variability among
      students at initial-baseline probe and also among growth trajectories within
      treatment subphases. Growth HLM showed that receptive vocabulary was a
      significant predictor of initial knowledge of sight words, and print knowledge
      significantly predicted growth rates in both treatment subphases. Next, to show
      the benefits of combining these methodologies to examine a different behavioral
      topography within a more commonly used SCR design, the authors used repeated
      measures HLM and visual analysis to examine simulated data within an ABAB design.
      Visual analysis revealed a functional relation between a hypothetical
      intervention (e.g., token reinforcement) and a hypothetical dependent variable
      (e.g., performance of a target response). HLM supported the existence of a
      functional relation through tests of statistical significance and detected
      significant variance among participants' response to the intervention that would
      be impossible to identify visually. This study highlights the relevance of these
      procedures to the identification of evidence-based interventions.

PMID- 22977267
TI  - Numbing and dysphoria symptoms of posttraumatic stress disorder among Iraq and
      Afghanistan War veterans: a review of findings and implications for treatment.
AB  - Iraq and Afghanistan war veterans experience significant rates of posttraumatic
      stress disorder (PTSD) and other trauma-related mental health conditions.
      Understanding how specific PTSD symptomatology affects physical health and
      psychosocial functioning may be useful in improving the conceptualization of PTSD
      nosology and informing treatment approaches for this population. Confirmatory
      factor analytic evidence supports four-factor models of PTSD symptoms that
      classify emotional numbing and/or dysphoria symptoms as a distinct PTSD symptom
      cluster, and these symptoms appear to be related to poorer psychological
      adjustment among returning Iraq and Afghanistan war veterans. This review briefly
      describes current conceptualizations of numbing/dysphoria symptoms of PTSD and
      summarizes research on the factor structure of PTSD symptoms. Then, the
      literature on the influence of numbing/dysphoria symptoms on physical and
      psychological health among these veterans is reviewed, and implications for
      treatment and directions for future research are presented.

PMID- 22977268
TI  - Executive deficits in early onset bipolar disorder versus ADHD: impact of
      processing speed and lifetime psychosis.
AB  - Executive deficits are reported in both early onset bipolar disorder (BD) and
      attention-deficit hyperactivity disorder (ADHD), and controversies regarding
      comorbidity and symptom overlap have complicated the research on executive
      function in BD. Reports of the negative impact of executive difficulties on
      academic functioning indicate a need for a greater focus on executive
      difficulties in early onset psychiatric disorders. Executive function and
      processing speed in youths with BD (n = 4), ADHD (n = 26) and BD + ADHD (n = 13)
      were compared with controls (n = 69). All clinical groups demonstrated executive
      impairment. The combined group was most impaired. There were no significant
      differences between the groups. Executive deficit in the BD group was associated
      with a history of psychotic symptoms. The BD-nonpsychotic group was impaired only
      with regard to processing speed. Processing speed adjustment improved working
      memory and normalized interference control in both BD and ADHD. CONCLUSION:
      executive deficits in BD may be determined by a history of psychotic symptoms
      rather than by comorbid ADHD. Some aspects of executive problems appear speed
      related.

PMID- 22977269
TI  - Effects of levothyroxine on bone mineral density, muscle force, and bone turnover
      markers: a cohort study.
AB  - CONTEXT: Previous studies of the effects of levothyroxine (LT(4)) therapy on bone
      and bone metabolism have provided conflicting results. OBJECTIVE: This study
      evaluated the potential effects and dose-response relationship of LT(4) therapy
      on bone mineral density (BMD) as well as bone and muscle strength. DESIGN AND
      SETTING: We conducted a prospective, nonrandomized, controlled cohort study with
      1.1 +/- 0.2-yr follow-up at an academic outpatient clinic in Germany.
      PARTICIPANTS: Ninety-seven men and premenopausal women were enrolled in the study
      after thyroidectomy and radioiodine remnant ablation for well-differentiated
      thyroid carcinoma (DTC) or strumectomy for nontoxic goiter. Patients were matched
      with 89 healthy controls. INTERVENTIONS: Twenty-eight men and 46 women on TSH
      suppressive doses of LT(4) had DTC, and 23 women were on LT(4) replacement
      therapy for nontoxic goiter. MAIN OUTCOME MEASURE: This study assessed total and
      trabecular volumetric BMD (vBMD) as well as bone strength at the ultradistal
      radius, areal BMD at the lumbar spine and both hips, and the grip strength of the
      nondominant forearm. The dependent variables were annualized rates of change.
      RESULTS: LT(4) therapy did not impair the areal BMD, bone strength, or grip
      strength of patients compared with controls. Women with DTC showed a significant
      loss of total vBMD, whereas men with DTC developed marginally less bone strength
      than women. Carboxy-terminal telopeptide indicated greater bone resorption in DTC
      patients compared with controls. CONCLUSIONS: There was little evidence of
      adverse LT(4) effects on bone; however, premenopausal women with DTC might be at
      risk for reduced vBMD in their ultradistal radii.

PMID- 22977270
TI  - Identification of a signaling axis HIF-1alpha/microRNA-210/ISCU independent of
      SDH mutation that defines a subgroup of head and neck paragangliomas.
AB  - BACKGROUND: Head and neck paragangliomas (HNPGLs) are rare tumors associated with
      the parasympathetic nervous system. Most are sporadic, but about one third result
      from germline mutations in succinate dehydrogenase (SDH) genes (SDHB, SDHC, SDHD,
      SDHA, or SDHAF2). Although a molecular connection between SDH dysfunction and
      tumor development is still unclear, the most accepted hypothesis proposes a
      central role of the pseudohypoxic pathway. SDH dysfunction induces abnormal
      stabilization of the hypoxia-inducible factors (HIFs) that regulate target genes
      involved in proliferation, apoptosis, angiogenesis, and metabolism. The
      involvement of these pathways in the development of sporadic HNPGLs is presently
      unknown. OBJECTIVE: To get some insights into the hypoxic/pseudohypoxic molecular
      basis of HNPGLs, we attempted to define the gene, microRNA (miRNA), and HIF
      1alpha expression patterns that distinguish tumors from normal paraganglia
      tissue. DESIGN: Genome microarray and TaqMan low-density arrays were used to
      analyze gene and miRNA expression, respectively, in 17 HNPGL tumor tissues and
      three normal human carotid bodies. Twelve HNPGLs were used for validation of
      data. HIF-1alpha, SDHB, and iron-sulfur cluster scaffold protein (ISCU) protein
      expression was analyzed by immunohistochemistry. RESULTS: We found activation of
      a canonical HIF-1alpha-related gene expression signaling only in a subset of
      HNPGLs from patients that did not harbor germline or somatic SDH mutations. The
      pseudohypoxic signature consisted in the overexpression of both HIF-1alpha-target
      genes and the HIF-1alpha-inducible miRNA, miR-210, and down-regulation of the miR
      210 target gene, ISCU1/2. A decreased level of the iron-sulfur-containing protein
      SDHB was found by immunohistochemical analysis performed in two of these tumors.
      CONCLUSIONS: Collectively, this study unveiled a putative signaling axis of HIF
      1alpha/miRNA-210/ISCU in a subset of HNPGLs that could have an impact on SDHB
      protein stability by a mechanism independent of SDH mutations, thus providing a
      foundation to better understand the functional interplay between HIF, miR-210,
      and mitochondria and its relevance in the pathogenesis of HNPGLs.

PMID- 22977271
TI  - Higher free thyroxine levels predict increased incidence of dementia in older
      men: the Health in Men Study.
AB  - CONTEXT: Both hypothyroidism and subclinical hyperthyroidism hinder cognitive
      function. OBJECTIVE: We aimed to determine whether more subtle alterations of
      thyroid hormone levels predict increased incidence of dementia in aging men.
      PARTICIPANTS AND DESIGN: Community-dwelling men aged 70-89 yr participated in
      this prospective longitudinal study. MAIN OUTCOME MEASURES: The Standardized Mini
      Mental State Examination was performed at baseline (2001-2004), and circulating
      TSH and free T(4) (FT(4)) were assayed. Men with known thyroid disease or
      dementia, or Standardized Mini-Mental State Examination scores below 24 were
      excluded from follow-up. New-onset dementia, defined by International
      Classification of Disease (ICD) codes, was ascertained using data linkage (2001
      2009). RESULTS: During follow-up, 145 of 3401 men (4.3%) were diagnosed for the
      first time with dementia. Men who developed dementia had higher baseline FT(4)
      (16.5 +/- 2.2 vs. 15.9 +/- 2.2 pmol/liter, P = 0.004) but similar TSH (2.2 +/-
      1.4 vs. 2.3 +/- 1.6 mU/liter, P = 0.23) compared with men who did not receive
      this diagnosis. After adjusting for covariates, higher FT(4) predicted new-onset
      dementia (11% increased risk per 1 pmol/liter increase in FT(4), P = 0.005;
      quartiles Q2-4 vs. Q1: adjusted hazard ratio = 1.76, 95% confidence interval =
      1.03-3.00, P = 0.04). There was no association between TSH quartiles and incident
      dementia. When the analysis was restricted to euthyroid men (excluding those with
      subclinical hyper- or hypothyroidism), higher FT(4) remained associated with
      incident dementia (11% increase per unit increment, P = 0.03; Q2-4 vs. Q1:
      adjusted hazard ratio = 2.02, 95% confidence interval = 1.10-3.71, P = 0.024).
      CONCLUSIONS: Higher FT(4) levels predict new-onset dementia in older men,
      independently of conventional risk factors for cognitive decline. Additional
      studies are needed to explore potential underlying mechanisms and to clarify the
      utility of thyroid function testing in older men at risk of dementia.

PMID- 22977273
TI  - Reference ranges and determinants of testosterone, dihydrotestosterone, and
      estradiol levels measured using liquid chromatography-tandem mass spectrometry in
      a population-based cohort of older men.
AB  - CONTEXT: Testosterone (T) levels decline with increasing age. Controversy exists
      over the threshold for classifying T as low vs. normal in older men. The
      relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) remains
      unclear. OBJECTIVE: We assessed the associations of T, DHT, and E2 in men aged 70
      yr or older and established reference ranges for these in healthy older men.
      PARTICIPANTS: Community-dwelling men aged 70-89 yr residing in Perth, Western
      Australia, Australia, participated in the study. MAIN OUTCOME MEASURES: Plasma T,
      DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in
      early morning samples from 3690 men. RESULTS: Increasing age, higher body mass
      index and waist to hip ratio, dyslipidemia, diabetes, and higher LH were
      independently associated with lower levels of T and DHT. Increasing age,
      diabetes, and higher LH were associated with lower E2. In a reference group of
      394 men aged 76.1 +/- 3.2 yr reporting excellent or very good health with no
      history of smoking, diabetes, cardiovascular disease, cancer, depression, or
      dementia, the 2.5th percentile for T was 6.4 nmol/liter (184 ng/dl); DHT, 0.49
      nmol/liter; and E2, 28 pmol/liter. Applying these cutoffs to all 3690 men, those
      with low T or DHT had an increased odds ratio for frailty, diabetes, and
      cardiovascular disease. Men with both low T and DHT had a higher odds ratio for
      these outcomes. CONCLUSIONS: The 2.5th percentile in a reference group of healthy
      older men provides age-appropriate thresholds for defining low T, DHT, and E2.
      Additional studies are needed to test their potential applicability and clinical
      utility in older men.

PMID- 22977272
TI  - Metabolomic profiling of amino acids and beta-cell function relative to insulin
      sensitivity in youth.
AB  - CONTEXT: In longitudinal studies of adults, elevated amino acid (AA)
      concentrations predicted future type 2 diabetes mellitus (T2DM). OBJECTIVE: The
      aim of the present investigation was to examine whether increased plasma AA
      concentrations are associated with impaired beta-cell function relative to
      insulin sensitivity [i.e. disposition index (DI)], a predictor of T2DM
      development. DESIGN, SETTING, AND PARTICIPANTS: Metabolomic analysis for fasting
      plasma AAs was performed by tandem mass spectrometry in 139 normal-weight and
      obese adolescents with and without dysglycemia. First-phase insulin secretion was
      evaluated by a hyperglycemic (~225 mg/dl) clamp and insulin sensitivity by a
      hyperinsulinemic-euglycemic clamp. DI was calculated as the product of first
      phase insulin and insulin sensitivity. RESULTS: DI was positively associated with
      branched-chain AAs (leucine/isoleucine and valine; r = 0.27 and 0.29, P = 0.001),
      neutrally transported AAs (phenylalanine and methionine; r = 0.30 and 0.35, P <
      0.001), basic AAs (histidine and arginine; r = 0.28 and 0.23, P <= 0.007), serine
      (r = 0.35, P < 0.001), glycine (r = 0.26, P = 0.002), and branched-chain AAs
      derived intermediates C3, C4, and C5 acylcarnitine (range r = 0.18-0.19, P <=
      0.04). CONCLUSION: In youth, increased plasma AA concentrations are not
      associated with a heightened metabolic risk profile for T2DM; rather, they are
      positively associated with beta-cell function relative to insulin sensitivity.
      These contrasting observations between adults and youth may be a reflection of
      developmental differences along the lifespan dependent on the combined impact of
      the aging process together with the impact of progressive obesity.

PMID- 22977274
TI  - Racial disparities in diabetic complications in an underinsured population.
AB  - CONTEXT: It is unclear whether there is a racial difference in the incidence of
      diabetic complications in underinsured populations. OBJECTIVE: The objective of
      the study was to investigate racial disparities in the incidence of diabetic
      complications within the Louisiana State University (LSU) Hospital System. DESIGN
      AND PARTICIPANTS: This study (1997-2009) was conducted on a diabetic cohort
      enrolled in the LSU Hospital-Based Longitudinal Study. The cohort included 16,808
      non-Hispanic white men, 21,983 non-Hispanic white women, 20,621 African-American
      men, and 33,753 African-American women who were 30-96 yr of age and had a mean
      value of family income of $9641/yr at baseline. RESULTS: The study cohort had a
      mean follow-up of 4.4 years. The age- and sex-adjusted incidence rates and 95%
      confidence intervals of end-stage renal disease (ESRD), coronary heart disease
      (CHD), heart failure (HF), and stroke for white diabetic patients were 15.1 (14.3
      15.8), 80.9 (78.9-82.9), 48.0 (46.6-49.4), and 21.4 (20.5-22.2) per 1000 person
      years, respectively. Compared with white diabetic patients, African-American
      diabetic patients experienced higher incident rates of ESRD [17.3 (16.6-18.0)]
      and lower rates of CHD [47.5 (46.3-48.6)], HF [40.7 (39.6-41.8)], and stroke
      [19.1 (18.4-19.9)]. Female diabetic patients had lower rates of the four
      complications than male diabetic patients. Results of the Cox proportional hazard
      models confirmed sex and race disparity observed in the age-adjusted incidence
      rates. CONCLUSIONS: Despite equal access to care, diabetic African-Americans have
      a higher risk of ESRD than their white counterparts, whereas diabetic whites have
      higher risks of CHD, HF, and stroke than their African-American counterparts.

PMID- 22977275
TI  - Effect of insulin infusion on spillover of meal-derived fatty acids.
AB  - CONTEXT: Spillover of chylomicron triglyceride fatty acids directly into the
      circulation as free fatty acids (FFAs) during lipoprotein lipase hydrolysis may
      contribute to the elevated total FFAs seen in insulin-resistant states.
      OBJECTIVE: The objective of the study was to determine whether spillover is
      regulated by rates of intracellular lipolysis, we studied overweight and obese
      nondiabetic subjects (n = 7) on two occasions, during infusion of saline and
      insulin. DESIGN: During insulin infusion (20 mU . m(-2) . min(-1)), plasma
      glucose was clamped at the concentration achieved during saline infusion. On both
      study days, subjects sipped 1-2 oz of a liquid mixed meal every 15 min for 6.5 h
      to achieve steady-state chylomicron and FFA concentrations. Spillover was
      measured with infusions of [(3)H]triolein and [U-(13)C] oleate. RESULTS: Glucose
      concentrations were similar during saline compared with insulin (113 +/- 2 vs.
      113 +/- 1 mg/dl, P = NS). Insulin levels during saline and insulin infusion were
      18 +/- 3 and 44 +/- 5 MUU/ml, respectively. Glucose infusion rate during insulin
      infusion was 5.5 +/- 1.0 mg . kg fat-free mass(-1) . min(-1). Plasma FFA
      concentrations were lower during insulin compared with saline (75 +/- 8 vs. 124
      +/- 13 MUmol/liter, P = 0.002). Oleate rate of appearance was lower during
      insulin vs. saline (27 +/- 3 vs. 36 +/- 5 MUmol/min, P = 0.004). Spillover was
      similar during saline and insulin (26 +/- 2 vs. 25 +/- 2%, P = 0.60).
      CONCLUSIONS: These results indicate that suppression of intracellular lipolysis
      with insulin does not reduce lipoprotein lipase-mediated spillover in humans
      during meal absorption. It is possible that spillover did not decrease because of
      an impaired or absent antilipolytic effect of increased insulin concentrations in
      visceral fat.

PMID- 22977276
TI  - Risk factors for coronary heart disease and survival after myocardial infarction.
AB  - OBJECTIVES: Several risk factors for coronary heart disease (CHD) have been
      associated with improved in-hospital survival after myocardial infarction (MI).
      We aimed to confirm this paradox and assess whether it extends to long-term
      outcome. In addition, we investigated temporal mortality trends. METHODS: We
      examined the relation between the presence of four modifiable risk factors for
      CHD (hypertension, dyslipidaemia, diabetes mellitus and smoking) and mortality in
      14,434 consecutive patients admitted with MI to a coronary care unit from 1985 to
      2008. RESULTS: Two-thirds of MI patients (n = 10,003) had at least one risk
      factor for CHD on hospital admission. The presence of at least one compared to no
      CHD risk factors was associated with a favourable 30-day mortality rate (5% vs.
      7%, adjusted odds ratio 0.72, 95% confidence interval (CI): 0.62-0.83). There was
      significant interaction between the presence of CHD risk factors and decade of
      hospitalization (p = 0.001). The adjusted 10-year mortality hazard ratio (HR) of
      at least one CHD risk factor compared to none, was 1.2 (95% CI: 1.0--1.4), 0.89
      (0.65--1.2) and 0.89 (0.79--0.99) in 1985--1990, 1990--2000 and 2000--2008,
      respectively. Survival improved over time. Adjusted 10-year mortality fell
      (adjusted HR [2000--2008 vs. 1985--1990] 0.59 [95% CI: 0.52--0.66] in patients
      with, and 0.76 [95% CI: 0.65-0.89] in those without CHD risk factors).
      CONCLUSIONS: The presence of at least one modifiable CHD risk factor was
      associated with improved outcome after MI. Patients with CHD risk factors
      benefited from more substantial mortality reductions during the past few decades.

PMID- 22977278
TI  - Impact of operator and site experience on outcomes after angioplasty and stenting
      in the SAMMPRIS trial.
AB  - BACKGROUND AND PURPOSE: To investigate the relationship between physician and
      site experience and the risk of 30 day hemorrhagic and ischemic strokes in the
      stenting arm of the Stenting and Aggressive Medical Management for the Prevention
      of Recurrent Ischemic Stroke (SAMMPRIS) trial. METHODS: Study records and an
      investigator survey were examined for physician and site related factors,
      including: number of Wingspan and aneurysm stents submitted for credentialing,
      number of study procedures performed in SAMMPRIS, years in practice after
      training, primary specialty, and site enrollment. Bivariate and multivariate
      analyses were performed to determine if these factors were associated with the 30
      day rate of cerebrovascular events after angioplasty and stenting. RESULTS: 213
      patients underwent angioplasty alone (n=5) or angioplasty and stenting (n=208)
      with study devices by 63 interventionists at 48 sites. For credentialing, the
      median number of Wingspan and similar aneurysm stent cases submitted by study
      interventionists were 10 and 6, respectively. Interventionists with higher
      numbers (>10) of Wingspan cases submitted for credentialing tended to have higher
      rates of 30 day events (19.0% vs 9.9%) than those with <10 cases. High enrolling
      sites in the trial tended to have lower rates of hemorrhagic stroke (9.8% at
      sites enrolling <12 patients vs 2.7% at sites enrolling >12 patients).
      CONCLUSIONS: Interventionists credentialed with less Wingspan experience were not
      responsible for the high rate of periprocedural stroke in SAMMPRIS. Hemorrhagic
      stroke may be related to low enrollment in the trial but not previous Wingspan
      experience.

PMID- 22977279
TI  - A comparative study of ethylene growth response kinetics in eudicots and monocots
      reveals a role for gibberellin in growth inhibition and recovery.
AB  - Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls
      has revealed new aspects about ethylene signaling. This study expands upon these
      results by examining ethylene growth response kinetics of seedlings of several
      plant species. Although the response kinetics varied between the eudicots
      studied, all had prolonged growth inhibition for as long as ethylene was present.
      In contrast, with continued application of ethylene, white millet (Panicum
      miliaceum) seedlings had a rapid and transient growth inhibition response, rice
      (Oryza sativa 'Nipponbare') seedlings had a slow onset of growth stimulation, and
      barley (Hordeum vulgare) had a transient growth inhibition response followed,
      after a delay, by a prolonged inhibition response. Growth stimulation in rice
      correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2
      (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7
      transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused
      millet seedlings to have a prolonged growth inhibition response when ethylene was
      applied. A transient ethylene growth inhibition response has previously been
      reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants.
      Paclobutrazol caused these mutants to have a prolonged response to ethylene,
      whereas constitutive GA signaling in this background eliminated ethylene
      responses. Sensitivity to paclobutrazol inversely correlated with the levels of
      EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol
      and mutants deficient in GA levels or signaling had a delayed growth recovery
      after ethylene removal. It is interesting to note that ethylene caused
      alterations in gene expression that are predicted to increase GA levels in the
      ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels
      leading to modulation of ethylene growth inhibition kinetics.

PMID- 22977280
TI  - Targeted systems biology profiling of tomato fruit reveals coordination of the
      Yang cycle and a distinct regulation of ethylene biosynthesis during
      postclimacteric ripening.
AB  - The concept of system 1 and system 2 ethylene biosynthesis during climacteric
      fruit ripening was initially described four decades ago. Although much is known
      about fruit development and climacteric ripening, little information is available
      about how ethylene biosynthesis is regulated during the postclimacteric phase. A
      targeted systems biology approach revealed a novel regulatory mechanism of
      ethylene biosynthesis of tomato (Solanum lycopersicum) when fruit have reached
      their maximal ethylene production level and which is characterized by a decline
      in ethylene biosynthesis. Ethylene production is shut down at the level of 1
      aminocyclopropane-1-carboxylic acid oxidase. At the same time, 1
      aminocyclopropane-1-carboxylic acid synthase activity increases. Analysis of the
      Yang cycle showed that the Yang cycle genes are regulated in a coordinated way
      and are highly expressed during postclimacteric ripening. Postclimacteric red
      tomatoes on the plant showed only a moderate regulation of 1-aminocyclopropane-1
      carboxylic acid synthase and Yang cycle genes compared with the regulation in
      detached fruit. Treatment of red fruit with 1-methylcyclopropane and ethephon
      revealed that the shut-down mechanism in ethylene biosynthesis is developmentally
      programmed and only moderately ethylene sensitive. We propose that the
      termination of autocatalytic ethylene biosynthesis of system 2 in ripe fruit
      delays senescence and preserves the fruit until seed dispersal.

PMID- 22977281
TI  - Effects of reduced chloroplast gene copy number on chloroplast gene expression in
      maize.
AB  - Chloroplasts and other members of the plastid organelle family contain a small
      genome of bacterial ancestry. Young chloroplasts contain hundreds of genome
      copies, but the functional significance of this high genome copy number has been
      unclear. We describe molecular phenotypes associated with mutations in a nuclear
      gene in maize (Zea mays), white2 (w2), encoding a predicted organellar DNA
      polymerase. Weak and strong mutant alleles cause a moderate (approximately 5
      fold) and severe (approximately 100-fold) decrease in plastid DNA copy number,
      respectively, as assayed by quantitative PCR and Southern-blot hybridization of
      leaf DNA. Both alleles condition a decrease in most chloroplast RNAs, with the
      magnitude of the RNA deficiencies roughly paralleling that of the DNA deficiency.
      However, some RNAs are more sensitive to a decrease in genome copy number than
      others. The rpoB messenger RNA (mRNA) exhibited a unique response, accumulating
      to dramatically elevated levels in response to a moderate reduction in plastid
      DNA. Subunits of photosynthetic enzyme complexes were reduced more severely than
      were plastid mRNAs, possibly because of impaired translation resulting from
      limiting ribosomal RNA, transfer RNA, and ribosomal protein mRNA. These results
      indicate that chloroplast genome copy number is a limiting factor for the
      expression of a subset of chloroplast genes in maize. Whereas in Arabidopsis
      (Arabidopsis thaliana) a pair of orthologous genes function redundantly to
      catalyze DNA replication in both mitochondria and chloroplasts, the w2 gene is
      responsible for virtually all chloroplast DNA replication in maize. Mitochondrial
      DNA copy number was reduced approximately 2-fold in mutants harboring strong w2
      alleles, suggesting that w2 also contributes to mitochondrial DNA replication.

PMID- 22977282
TI  - Scleritis: presentations, disease associations and management.
AB  - Scleritis is a serious inflammatory condition that is often painful, and in
      severe cases can result in permanent loss of vision. Approximately half the
      patients affected have no identifiable cause, but 30%-40% have an underlying
      systemic autoimmune condition. Scleritis may be the initial manifestation of
      Wegener's granulomatosis or rheumatoid arthritis, and all patients with scleritis
      require a thorough systemic evaluation. Scleritis has a variable presentation and
      disease course, and may be an acute monophasic illness, a relapsing remitting
      process, or take a chronic course. Treatment options include local therapy with
      subconjunctival steroid injections for non-necrotising scleritis, and systemic
      anti-inflammatory or immunosuppressive therapy. Biologic agents have been used
      with success in some refractory cases. Ocular and systemic morbidity is reduced
      by timely treatment with immunosuppressant medications.

PMID- 22977283
TI  - The risk of serious adverse outcomes associated with hypoxaemia and hyperoxaemia
      in acute exacerbations of COPD.
AB  - BACKGROUND: Prehospital high concentration oxygen therapy leads to worse clinical
      outcomes in patients presenting with acute exacerbations of chronic obstructive
      pulmonary disease (AECOPD). Less is known about the risks of hypoxaemia despite
      oxygen treatment. Current respiratory and ambulance guidelines recommend
      titration of supplemental oxygen to a target oxygen saturation range of 88%-92%.
      AIM: To explore the association between PaO(2) and risk of serious adverse
      clinical outcomes in AECOPD. METHODS: A retrospective review of consecutive
      patients presenting via ambulance to the Wellington Regional Hospital Emergency
      Department with AECOPD between June 2005 and January 2008. Patients with an
      arterial blood gas taken within 4 h of triage were included in the study and were
      categorised as hypoxaemic (PaO(2)<60 mm Hg), normoxaemic (PaO(2) 60-100 mm Hg) or
      hyperoxaemic (PaO(2)>100 mm Hg). Serious adverse outcome was defined as a
      composite of hypercapnic respiratory failure, assisted ventilation or inpatient
      death. Multivariate logistic regression analysis examined the association between
      PaO(2) category and the composite outcome. RESULTS: Of the 680 patients
      presenting with AECOPD in the review period, 254 presentations in 180 patients
      had data suitable for analysis. Hyperoxaemia occurred in 61/254 (24%)
      presentations and was strongly associated with serious adverse outcome compared
      with normoxaemia (OR 9.17, 95% CI 4.08 to 20.6). Hypoxaemia was also associated
      with an increased risk of serious adverse outcome compared with normoxaemia (OR
      2.16, 95% CI 1.11 to 4.20). Compared with the recommended target oxygen
      saturation range of  88%-92%, the risk of a serious adverse outcome was increased
      in both the <88% group (OR 2.0, 95% CI 1.03 to 3.80) and the >96% group (OR 2.37,
      95% CI 1.34 to 4.20). CONCLUSIONS: In patients presenting via ambulance to the
      Emergency Department with AECOPD, serious adverse clinical outcomes are
      associated with both hypoxaemia and hyperoxaemia. These data provide further
      support for the principle of titrating supplemental oxygen therapy to target
      oxygen saturations.

PMID- 22977285
TI  - Photo quiz: unexpected fatal pneumonia in an immunocompetent adult: a tale of a
      father and a son.

PMID- 22977284
TI  - Paediatric intra-axial posterior fossa tumours: pictorial review.
AB  - Paediatric brain tumours commonly arise in the posterior cranial fossa. Early
      diagnosis is often challenging due to initial non-specific clinical symptoms,
      especially in very young children. The typical MR features of tumours in this
      region including medulloblastoma, ependymoma, juvenile pilocytic subtype of
      cerebellar astrocytoma, brain stem glioma and atypical teratoid-rhabdoid tumour
      are illustrated. Diffusion-weighted imaging and apparent diffusion coefficient
      values combined with signal characteristics on conventional MR sequences can
      usually differentiate low-grade from high-grade tumours. Prompt diagnosis is
      crucial as total surgical resection, which is only possible in localised disease,
      improves prognosis. A practical MR flow chart is introduced for differentiating
      different types of posterior cranial fossa tumours, which might be useful in
      clinical practice.

PMID- 22977287
TI  - Matrix metalloproteinase-9 expression is increased in astrocytic glioma and
      associated with prognosis of patients.
AB  - OBJECTIVE: Glioma is the most common type of primary central nervous system
      tumor. This study was aimed at investigating the expression of matrix
      metalloproteinase-9 in astrocytic glioma samples and its association with
      clinicopathological characteristics as well as survival of patients. METHODS:
      Astrocytic glioma samples from 272 patients who had not received chemotherapy or
      radiotherapy were collected, in which matrix metalloproteinase-9 expression was
      assessed by immunochemistry assays. The association of staining evaluation
      results with clinicopathological characteristics was analyzed by appropriate
      statistical analysis. Kaplan-Meier analysis and Cox proportional hazards
      regression models were used to investigate the association between matrix
      metalloproteinase-9 expression and survival of patients. RESULTS: Results showed
      that matrix metalloproteinase-9 expression is increased in astrocytic glioma and
      associated with tumor progression as its expression increased from Grade II to
      Grade IV glioma (P<0.001). Kaplan-Meier analysis showed that patients with glioma
      with higher matrix metalloproteinase-9 expression tend to have shorter overall
      survival time (P<0.001). In multivariate analysis, matrix metalloproteinase-9
      expression was proved to be an independent prognostic factor for patients with
      astrocytic glioma (P<0.001). CONCLUSIONS: This study confirmed the overexpression
      of matrix metalloproteinase-9 and its association with tumor progression in
      astrocytic glioma. It also provided the first evidence that matrix
      metalloproteinase-9 expression in glioma was an independent prognostic factor of
      patients, which might be a potential diagnostic and therapeutic target of
      astrocytic glioma.

PMID- 22977288
TI  - Estimation of Attitude and External Acceleration Using Inertial Sensor
      Measurement During Various Dynamic Conditions.
AB  - This paper proposes a Kalman filter-based attitude (i.e., roll and pitch)
      estimation algorithm using an inertial sensor composed of a triaxial
      accelerometer and a triaxial gyroscope. In particular, the proposed algorithm has
      been developed for accurate attitude estimation during dynamic conditions, in
      which external acceleration is present. Although external acceleration is the
      main source of the attitude estimation error and despite the need for its
      accurate estimation in many applications, this problem that can be critical for
      the attitude estimation has not been addressed explicitly in the literature.
      Accordingly, this paper addresses the combined estimation problem of the attitude
      and external acceleration. Experimental tests were conducted to verify the
      performance of the proposed algorithm in various dynamic condition settings and
      to provide further insight into the variations in the estimation accuracy.
      Furthermore, two different approaches for dealing with the estimation problem
      during dynamic conditions were compared, i.e., threshold-based switching approach
      versus acceleration model-based approach. Based on an external acceleration
      model, the proposed algorithm was capable of estimating accurate attitudes and
      external accelerations for short accelerated periods, showing its high
      effectiveness during short-term fast dynamic conditions. Contrariwise, when the
      testing condition involved prolonged high external accelerations, the proposed
      algorithm exhibited gradually increasing errors. However, as soon as the
      condition returned to static or quasi-static conditions, the algorithm was able
      to stabilize the estimation error, regaining its high estimation accuracy.

PMID- 22977289
TI  - Noise filtering strategies in adaptive biochemical signaling networks:
      Application to E. coli chemotaxis.
AB  - Two distinct mechanisms for filtering noise in an input signal are identified in
      a class of adaptive sensory networks. We find that the high-frequency noise is
      filtered by the output degradation process through time-averaging; while the low
      frequency noise is damped by adaptation through negative feedback. Both filtering
      processes themselves introduce intrinsic noises, which are found to be unfiltered
      and can thus amount to a significant internal noise floor even without signaling.
      These results are applied to E. coli chemotaxis. We show unambiguously that the
      molecular mechanism for the Berg-Purcell time-averaging scheme is the
      dephosphorylation of the response regulator CheY-P, not the receptor adaptation
      process as previously suggested. The high-frequency noise due to the stochastic
      ligand binding-unbinding events and the random ligand molecule diffusion is
      averaged by the CheY-P dephosphorylation process to a negligible level in E.
      coli. We identify a previously unstudied noise source caused by the random motion
      of the cell in a ligand gradient. We show that this random walk induced signal
      noise has a divergent low-frequency component, which is only rendered finite by
      the receptor adaptation process. For gradients within the E. coli sensing range,
      this dominant external noise can be comparable to the significant intrinsic noise
      in the system. The dependence of the response and its fluctuations on the key
      time scales of the system are studied systematically. We show that the chemotaxis
      pathway may have evolved to optimize gradient sensing, strong response, and noise
      control in different time scales.

PMID- 22977290
TI  - Modeling the Nonlinear Time Dynamics of Multidimensional Hormonal Systems.
AB  - In most hormonal systems (as well as many physiological systems more generally),
      the chemical signals from the brain, which drive much of the dynamics, can not be
      observed in humans. By the time the molecules reach peripheral blood, they have
      been so diluted so as to not be assayable. It is not possible to invasively
      (surgically) measure these agents in the brain. This creates a difficult
      situation in terms of assessing whether or not the dynamics may have changed due
      to disease or aging. Moreover, most biological feedforward and feedback
      interactions occur after time delays, and the time delays need to be properly
      estimated. We address the following two questions: (1) Is it possible to devise a
      combination of clinical experiments by which, via exogenous inputs, the hormonal
      system can be perturbed to new steady-states in such a way that information about
      the unobserved components can be ascertained; and, (2) Can one devise methods to
      estimate (possibly, time-varying) time delays between components of a
      multidimensional nonlinear time series, which are more robust than traditional
      methods? We present methods for both questions, using the Stress (ACTH-cortisol)
      hormonal system as a prototype, but the approach is more broadly applicable.

PMID- 22977293
TI  - Simplified THz Instrumentation for High-Field DNP-NMR Spectroscopy.
AB  - We present an alternate simplified concept to irradiate a nuclear magnetic
      resonance sample with terahertz (THz) radiation for dynamic nuclear polarization
      (DNP) experiments using the TE(01) circular waveguide mode for transmission of
      the THz power and the illumination of the DNP sample by either the TE(01) or
      TE(11) mode. Using finite element method and 3D electromagnetic simulations we
      demonstrate that the average value of the transverse magnetic field induced by
      the THz radiation and responsible for the DNP effect using the TE(11) or the
      TE(01) mode are comparable to that generated by the HE(11) mode and a corrugated
      waveguide. The choice of the TE(11)/TE(01) mode allows the use of a smooth
      walled, oversized waveguide that is easier to fabricate and less expensive than a
      corrugated waveguide required for transmission of the HE(11) mode. Also, the
      choice of the TE(01) mode can lead to a simplification of gyrotron oscillators
      that operate in the TE(0n) mode, by employing an on-axis rippled-wall mode
      converter to convert the TE(0n) mode into the TE(01) mode either inside or
      outside of the gyrotron tube. These novel concepts will lead to a significant
      simplification of the gyrotron, the transmission line and the THz coupler, which
      are the three main components of a DNP system.

PMID- 22977294
TI  - Automatic segmentation of seeds and fluoroscope tracking (FTRAC) fiducial in
      prostate brachytherapy x-ray images.
AB  - C-arm X-ray fluoroscopy-based radioactive seed localization for intraoperative
      dosimetry of prostate brachytherapy is an active area of research. The
      fluoroscopy tracking (FTRAC) fiducial is an image-based tracking device composed
      of radio-opaque BBs, lines, and ellipses that provides an effective means for
      pose estimation so that three-dimensional reconstruction of the implanted seeds
      from multiple X-ray images can be related to the ultrasound-computed prostate
      volume. Both the FTRAC features and the brachytherapy seeds must be segmented
      quickly and accurately during the surgery, but current segmentation algorithms
      are inhibitory in the operating room (OR). The first reason is that current
      algorithms require operators to manually select a region of interest (ROI),
      preventing automatic pipelining from image acquisition to seed reconstruction.
      Secondly, these algorithms fail often, requiring operators to manually correct
      the errors. We propose a fast and effective ROI-free automatic FTRAC and seed
      segmentation algorithm to minimize such human intervention. The proposed
      algorithm exploits recent image processing tools to make seed reconstruction as
      easy and convenient as possible. Preliminary results on 162 patient images show
      this algorithm to be fast, effective, and accurate for all features to be
      segmented. With near perfect success rates and subpixel differences to manual
      segmentation, our automatic FTRAC and seed segmentation algorithm shows promising
      results to save crucial time in the OR while reducing errors.

PMID- 22977295
TI  - Generalized Statistical Label Fusion using Multiple Consensus Levels.
AB  - Segmentation plays a critical role in exposing connections between biological
      structure and function. The process of label fusion collects and combines
      multiple observations into a single estimate. Statistically driven techniques
      provide mechanisms to optimally combine segmentations; yet, optimality hinges
      upon accurate modeling of rater behavior. Traditional approaches, e.g., Majority
      Vote and Simultaneous Truth and Performance Level Estimation (STAPLE), have been
      shown to yield excellent performance in some cases, but do not account for
      spatial dependences of rater performance (i.e., regional task difficulty).
      Recently, the COnsensus Level, Labeler Accuracy and Truth Estimation (COLLATE)
      label fusion technique augmented the seminal STAPLE approach to simultaneously
      estimate regions of relative consensus versus confusion along with rater
      performance. Herein, we extend the COLLATE framework to account for multiple
      consensus levels. Toward this end, we posit a generalized model of rater behavior
      of which Majority Vote, STAPLE, STAPLE Ignoring Consensus Voxels, and COLLATE are
      special cases. The new algorithm is evaluated with simulations and shown to yield
      improved performance in cases with complex region difficulties. Multi-COLLATE
      achieve these results by capturing different consensus levels. The potential
      impacts and applications of generative model to label fusion problems are
      discussed.

PMID- 22977296
TI  - 3-D Deep Penetration Photoacoustic Imaging with a 2-D CMUT Array.
AB  - In this work, we demonstrate 3-D photoacoustic imaging of optically absorbing
      targets embedded as deep as 5 cm inside a highly scattering background medium
      using a 2-D capacitive micromachined ultrasonic transducer (CMUT) array with a
      center frequency of 5.5 MHz. 3-D volumetric images and 2-D maximum intensity
      projection images are presented to show the objects imaged at different depths.
      Due to the close proximity of the CMUT to the integrated frontend circuits, the
      CMUT array imaging system has a low noise floor. This makes the CMUT a promising
      technology for deep tissue photoacoustic imaging.

PMID- 22977297
TI  - Universal Prevention of Anxiety and Depression in a Recreational Camp Setting: An
      Initial Open Trial.
AB  - BACKGROUND: Anxiety and depressive disorders may pose a long-term, deleterious
      impact on youth, prompting a need for early and effective prevention of such
      concerns. A growing body of research has examined universal prevention programs
      targeting these emotional disorders in childhood. While most universal prevention
      programs are offered within the school setting, there is also a rationale for
      developing and investigating prevention programs within novel settings, including
      a recreational context.  OBJECTIVE: This initial investigation utilized the
      Emotion Detectives Prevention Program (EDPP), a universal prevention protocol
      focusing on anxiety and depression symptoms within a recreational summer camp.
      The aims of this pilot study were to assess the EDPP's feasibility and
      participant satisfaction following its initial administration in a camp setting. 
      METHOD: Forty children (ages 7-10 years, 70.7% male) were recruited from an
      existent recreational sports camp and participated in a non-randomized, open
      trial of the EDPP. The EDPP, a 15-session program, presents cognitive-behavioral
      strategies in a manner that emphasizes strategy applicability across a range of
      emotional experiences.  RESULTS: Participating children reported a significant
      decrease in anxiety symptoms at post-prevention. No significant change in
      depression symptoms or other emotion regulation indices were reported. Moderate
      to high participant satisfaction was indicated.  CONCLUSIONS: The EDPP appears to
      be a feasible program for the prevention of child-reported anxiety symptoms in a
      camp setting. Given the novelty of the prevention context, issues inherent in the
      conduct of research in a recreational camp setting and future directions for
      research in this setting are discussed.

PMID- 22977298
TI  - Nano chitosan peptide as a potential therapeutic carrier for retinal delivery to
      treat age-related macular degeneration.
AB  - PURPOSE: We describe the synthesis and use of an efficient nano carrier molecule
      for retinal delivery of a nano chitosan peptide that has potential application
      for treating age-related macular degeneration (AMD). We chose serine-threonine
      tyrosine as the peptide sequence because it is well known to act as a
      transduction signaling agent within and between retinal pigmented epithelium
      cells. METHODS: A nanoformulation of a water-soluble chitosan conjugated with a
      peptide (serine-threonine-tyrosine) was synthesized by a method developed in our
      laboratory and characterized with dynamic light scattering, zeta potential,
      transmission electron microscopy, nuclear magnetic resonance, and Fourier
      transform infrared spectroscopy. The in vitro efficacy of the formulation was
      evaluated in retinal cells with confocal microscopy by studying the formulation's
      action on tyrosine kinase activity. RESULTS: The conjugated nano chitosan peptide
      showed evidence of tyrosine kinase activity as seen by fluorescent signals under
      confocal microscopy, while nano chitosan or peptide alone did not show such
      activity. CONCLUSIONS: Conjugated nano chitosan peptide may promote binding and
      engulfment. This molecule is an excellent carrier for retinal drug delivery and
      has the potential to treat age-related macular degeneration.

PMID- 22977299
TI  - The Usher gene cadherin 23 is expressed in the zebrafish brain and a subset of
      retinal amacrine cells.
AB  - PURPOSE: To characterize the expression pattern of cadherin 23 (cdh23) in the
      zebrafish visual system, and to determine whether zebrafish cdh23 mutants have
      retinal defects similar to those present in the human disease Usher syndrome 1D.
      METHODS: In situ hybridization and immunohistochemistry were used to characterize
      cdh23 expression in the zebrafish, and to evaluate cdh23 mutants for retinal
      degeneration. Visual function was assessed by measurement of the optokinetic
      response in cdh23 siblings and mutants. RESULTS: We detected cdh23 mRNA
      expression in multiple nuclei of both the developing and adult central nervous
      system. In the retina, cdh23 mRNA was expressed in a small subset of amacrine
      cells, beginning at 70 h postfertilization and continuing through adulthood. No
      expression was detected in photoreceptors. The cdh23-positive population of
      amacrine cells was GABAergic. Examination of homozygous larvae expressing two
      different mutant alleles of cdh23-cdh23(tc317e) or cdh23(tj264a)-revealed no
      detectable morphological retinal defects or degeneration. In addition, the
      optokinetic response to moving gratings of varied contrast or spatial frequency
      was normal in both mutants. CONCLUSIONS: Unlike in other vertebrates, cdh23 is
      not detectable in zebrafish photoreceptors. Instead, cdh23 is expressed by a
      small subset of GABAergic amacrine cells. Moreover, larvae with mutations in
      cdh23 do not exhibit any signs of gross retinal degeneration or dysfunction. The
      role played by cdh23 in human retinal function is likely performed by either a
      different gene or an unidentified cdh23 splice variant in the retina that is not
      affected by the above mutations.

PMID- 22977300
TI  - Systemic immunotherapy delays photoreceptor cell loss and prevents vascular
      pathology in Royal College of Surgeons rats.
AB  - PURPOSE: Degenerative retinopathies, including retinitis pigmentosa, age-related
      retinal degeneration, autoimmune retinopathy, and related diseases affect
      millions of people around the world. Currently, there is no effective treatment
      for most of those diseases. We investigated systemic recombinant T-cell receptor
      ligand (RTL) immunotherapy for preventing retinal degeneration and vascular
      damage in the Royal College of Surgeons (RCS) rat model of retinal degeneration.
      METHODS: RCS rats were treated with RTL220 tethered to interphotoreceptor
      retinoid binding protein (IRBP) peptide or control RTL101 without peptide by
      subcutaneous administration starting at the onset of photoreceptor degeneration
      or after the degenerative process began daily or every other day and performed
      for a 13-week period. The retinal cross sections and whole mounts were prepared
      to determine histopathology, leaking vessels, and formation of vascular
      complexes. Immunofluorescent studies evaluated microglia and monocyte
      chemoattractant protein-1 chemokine in treated retinas. Optokinetic studies were
      performed to determine visual acuity. RESULTS: Systemic treatment with RTL220
      prevented decreases in outer nuclear layer (ONL) thickness and showed a
      significantly higher number of nuclei than control rats treated with RTL101 or
      vehicle. RTL220 was also effective in protecting retinal vasculature from leakage
      and the formation of abnormal vascular complexes even when the treatment was
      administered after the degenerative process was initiated. Visual acuity
      measurement showed that rats treated with RTL220 performed significantly better
      than those with RTL101 and untreated age-matched controls at P60 and P90.
      Biodistribution studies showed that RTL220 cleared slowly from the administration
      site. Moreover, RTL220-treated retinas had a significantly reduced number of
      activated microglia in the subretinal space, decreased monocyte chemoattractant
      protein-1 production in the retina, inhibited T-cell responses, and reduced anti
      interphotoreceptor retinoid binding protein autoantibody titers. Treatment with
      the control RTL101 (without a specific peptide tethered) or vehicle alone did not
      inhibit microglia activation or protect photoreceptors or vasculature.
      CONCLUSIONS: RTL therapy augmented photoreceptor cell survival, protected
      vasculature, and increased visual function in the RTL rat. Targeting chronic
      autoimmunity with RTLs can be an effective therapeutic alternative in delaying
      retinal degeneration. Subcutaneous delivery of RTLs alone or combined with other
      drugs could be an attractive option for long-term therapy for retinal
      degenerative diseases.

PMID- 22977301
TI  - OnabotulinumtoxinA in the treatment of neurogenic bladder.
AB  - This review examines the evidence for use of onabotulinumtoxinA in the treatment
      of neurogenic lower urinary tract dysfunction. Since its first use in 1988 to
      treat detrusor sphincter dyssynergia, use of botulinum toxin has increased in
      this group of patients. We discuss the mechanism of action, patient selection,
      dosing, efficacy, and side effect profile of this now licensed treatment option.

PMID- 22977302
TI  - Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer
      patients.
AB  - Bone loss is a common side effect of cancer treatments, especially antihormonal
      treatments used in the treatment of breast and prostate cancer. Denosumab is a
      monoclonal antibody given subcutaneously that inhibits osteoclast activity by
      targeting the RANK ligand. It is effective in settings ranging from preventing
      skeletal-related complications in cancer patients with metastatic disease to
      increasing bone mineral density in patients with osteoporosis. In cancer patients
      with early stage disease, denosumab can attenuate bone loss from antihormonal
      treatments, and in prostate cancer, may reduce disease progression. Here, we will
      discuss the important role denosumab may play in the management of bone loss in
      patients with cancer.

PMID- 22977303
TI  - Self-assembled supramolecular nano vesicles for safe and highly efficient gene
      delivery to solid tumors.
AB  - The main obstacles for cationic polyplexes in gene delivery are in vivo
      instability and low solid-tumor accumulation. Safe vectors with high transfection
      efficiency and in vivo tumor accumulation are therefore highly desirable. In this
      study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N
      acryloylmorpholine) was synthesized by reversible addition-fragmentation chain
      transfer (RAFT) radical polymerization. The corresponding well-defined vesicles
      with narrow size distribution were tailored by finely regulating the packing
      parameter (beta) of copolymer (1/2 < beta < 1). Compared with traditional "gold
      standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing
      efficiency, DNase I degradation protection, and cellular uptake were improved by
      the supramolecular nano vesicles. In addition, the plasmid DNA transferring
      efficiency in 10% fetal bovine serum medium was enlarged five times to that of
      polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma
      cell lines. This improved in vitro transfection was mainly attributed to the
      densely packed bilayer. This stealth polyplex showed high serum stability via
      entropic repulsion, which further protected the polyplex from being destroyed
      during sterilization. As indicated by the IVIS((r)) Lumina II Imaging System
      (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration,
      intra-tumor accumulation of the stealth polyplex was clearly promoted. This study
      successfully circumvented the traditional dilemma of efficient gene transfection
      at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is
      accompanied with site cytotoxicity and low stability. As such, these simply
      tailored noncytotoxic nano vesicles show significant potential for use in
      practical gene therapy.

PMID- 22977304
TI  - Depressive symptoms and childhood sleep apnea syndrome.
AB  - BACKGROUND: The relationship between sleep and mood regulation is well known, and
      some reports suggest a key role of sleep-related breathing disorders (SRBD) in
      the development of the symptomatology of depression, even if no conclusive data
      are actually found in the clinical literature. The aim of this study was to
      assess the relationship between SRBD and depressive symptoms in a population of
      school-aged children. METHODS: The study population comprised 94 children
      affected by SRBD and 107 healthy children. To identify the severity of SRBD, an
      overnight respiratory evaluation was performed. All subjects filled out the
      Italian version of the Children Depression Inventory (CDI) to screen for the
      presence of depressive symptoms. RESULTS: The group with SRBD showed higher CDI
      scores than the group without SRBD, with a positive correlation found between CDI
      scores, apnea-hypopnea index, and oxygen desaturation index values. Logistic
      regression showed that an apnea-hypopnea index >= 3 and an oxygen desaturation
      index >= 1 could be risk factors for development of depressive symptoms.
      According to receiver-operating characteristic curve analysis, the cutoff point
      for the apnea-hypopnea index that could cause a pathological CDI score (>=19) was
      >5.66, and the cutoff point for the oxygen desaturation index was >4.2. The
      limitations of this study are that our data are derived from one single
      psychometric test and not from a complete psychiatric evaluation, and our
      subjects came from a small group in southern Italy. CONCLUSION: Our results
      suggest the importance of mood assessment in children affected by SRBD.

PMID- 22977305
TI  - Patient considerations and clinical impact of cholesteryl ester transfer protein
      inhibitors in the management of dyslipidemia: focus on anacetrapib.
AB  - Cardiovascular disease (CVD) is responsible for significant morbidity and
      mortality within the United States and worldwide. Although targeting low-density
      lipoprotein cholesterol (LDL-C) in the prevention of CVD has been shown to be
      effective, evidence exists to indicate that significant cardiovascular (CV) risk
      remains in patients receiving 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors (statins) - a risk that may be correlated with low levels of high
      density lipoprotein cholesterol (HDL-C). Among the various tactics under
      investigation to increase HDL-C, inhibition of cholesteryl ester transfer protein
      (CETP) appears the most adept to raise these levels. Although torcetrapib, a CETP
      inhibitor, demonstrated significant beneficial changes in HDL-C and LDL-C after
      12 months of therapy when coadministered with atorvastatin, patients in the
      torcetrapib arm experienced a rise in mortality, including increased risk of
      death from CV and non-CV causes as well as a significant rise in major CV events.
      Later studies established that the adverse effects of torcetrapib were produced
      from molecule-specific off-target effects and not to the mechanism of CETP
      inhibition. These untoward outcomes have not been detected with anacetrapib, the
      third of the CETP inhibitors to enter Phase III trials. Furthermore, treatment
      with anacetrapib revealed both a statistically significant decrease in LDL-C and
      increase in HDL-C over placebo. While the place in therapy of niacin and fibrates
      to reduce CV events is currently in question secondary to the Atherothrombosis
      Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and
      Impact on Global Health Outcomes and the Action to Control CV Risk in Diabetes
      trials, the ongoing large-scale, randomized-placebo, controlled-outcomes study
      with anacetrapib coadministered with statin treatment will not only test the
      hypothesis if CETP inhibition lowers residual CV risk but will also provide
      insight as to which patient subgroups might benefit the most from anacetrapib
      despite aggressive therapy with statins.

PMID- 22977306
TI  - Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized
      farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.
AB  - PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II
      study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally
      advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1
      year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020
      was to evaluate the addition of weekly low- dose gemcitabine with concurrent
      paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase
      inhibitor R115777 following chemoradiation. PATIENTS AND METHODS: Patients with
      unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible.
      Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40
      mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2
      received an identical chemoradiation regimen but then received maintenance
      R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until
      disease progression or unacceptable toxicity. RESULTS: One hundred ninety-five
      patients were entered into this study, and 184 were analyzable. Grade 4
      nonhematologic toxicities occurred in less than 5% of CXRT patients. The most
      common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4
      hepatic, metabolic, musculoskeletal, and neurologic toxicities were also
      reported. The median survival time was 11.5 months and 8.9 months for the CXRT
      and CXRT+R115777 arms, respectively. CONCLUSIONS: The CXRT arm achieved a median
      survival of almost 1-year, supporting chemoradiation as an important therapeutic
      modality for locally advanced pancreatic cancer. Maintenance R115777 is not
      effective and is associated with a broad range of toxicities. These findings
      provide clinical evidence that inhibition of farnesylation affects many metabolic
      pathways, underscoring the challenge of developing an effective K-ras inhibitor.

PMID- 22977307
TI  - Development of ceftazidime resistance in an acute Burkholderia pseudomallei
      infection.
AB  - Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is
      intrinsically resistant to many antibiotics. First-line antibiotic therapy for
      treating melioidosis is usually the synthetic beta-lactam, ceftazidime (CAZ), as
      almost all B. pseudomallei strains are susceptible to this drug. However,
      acquired CAZ resistance can develop in vivo during treatment with CAZ, which can
      lead to mortality if therapy is not switched to a different drug in a timely
      manner. Serial B. pseudomallei isolates obtained from an acute Thai melioidosis
      patient infected by a CAZ susceptible strain, who ultimately succumbed to
      infection despite being on CAZ therapy for the duration of their infection, were
      analyzed. Isolates that developed CAZ resistance due to a proline to serine
      change at position 167 in the beta-lactamase PenA were identified. Importantly,
      these CAZ resistant isolates remained sensitive to the alternative melioidosis
      treatments; namely, amoxicillin-clavulanate, imipenem, and meropenem. Lastly,
      real-time polymerase chain reaction-based assays capable of rapidly identifying
      CAZ resistance in B. pseudomallei isolates at the position 167 mutation site were
      developed. The ability to rapidly identify the emergence of CAZ resistant B.
      pseudomallei populations in melioidosis patients will allow timely alterations in
      treatment strategies, thereby improving patient outcomes for this serious
      disease.

PMID- 22977308
TI  - Cost of rheumatoid arthritis in a selected population from Argentina in the
      prebiologic therapy era.
AB  - BACKGROUND: The present study aimed to estimate the cost of rheumatoid arthritis
      and its components in a university hospital-based health management organization
      in Argentina, during the prebiologic era. METHODS: A one-year (2002)
      observational prevalence, cost-of illness study of patients with rheumatoid
      arthritis from the societal perspective was performed in a hospital-based health
      management organization population. Direct medical costs were obtained using
      administrative databases. Direct nonmedical and indirect costs were obtained from
      a semistructured questionnaire. Indirect costs included work absenteeism,
      permanent work disability, and housework lost for housewives, using the human
      capital approach. Costs are expressed in 2002 US dollars per patient per year.
      RESULTS: A total of 165 patients (84% females), of mean age 61 +/- 15 years and
      with a mean disease duration of 8.5 +/- 8.3 years were included. Mean total
      direct medical costs were US$1862 (95% confidence interval [CI] 828-2899). Mean
      direct nonmedical costs were US$222 (95% CI 149-294). Mean indirect costs were
      US$1008 (95% CI 606-1412). The annual mean total cost was US$3093 without
      biologics. Hospitalizations represented 73% of total direct medical costs while
      drugs and outpatient procedures represented 16% and 8% of total direct medical
      costs, respectively. Sixty percent of the total costs were related to direct
      medical costs, while indirect costs represented 33% of total costs. CONCLUSION:
      In our population, annual mean total costs in the prebiologic therapy era were
      mainly driven by direct medical costs. Even without the use of biologic agents,
      rheumatoid arthritis represents an important burden for society in developing
      countries.

PMID- 22977309
TI  - Cost-effectiveness of entecavir versus adefovir for the treatment of chronic
      hepatitis B in patients with decompensated cirrhosis from a third-party US payer
      perspective.
AB  - BACKGROUND: Decompensated cirrhosis is a serious clinical complication of chronic
      hepatitis B (CHB) that places a large economic burden on the US health care
      system. Although entecavir has been shown to improve health outcomes in a cost
      effective manner in mixed populations of CHB patients, the cost-effectiveness of
      entecavir has not been evaluated in CHB patients with decompensated cirrhosis.
      METHODS: This study assessed the cost-effectiveness of entecavir versus adefovir,
      from a US payer perspective, in CHB patients with decompensated cirrhosis, using
      a health-state transition Markov model with four health states: hepatocellular
      carcinoma (HCC), HCC-free survival, post-liver transplant, and death. The model
      considered a hypothetical patient population similar to that included in a
      randomized controlled trial in the target population (ETV-048): predominantly
      male (74%), Asian (54%), mean age 52 years, hepatic decompensation (Child-Pugh
      score >= seven), hepatitis B e antigen-positive or -negative, treatment-naive or
      lamivudine-experienced, and no liver transplant history. Clinical inputs were
      based on cumulative safety results for ETV-048 and published literature. Costs
      were obtained from published literature. Costs and outcomes were discounted at 3%
      per annum. RESULTS: For 1000 patients over a 3-year time horizon, predicted
      overall survival and HCC-free survival were longer with entecavir than with
      adefovir (2.35 versus 2.30 years and 2.11 versus 2.03 years, respectively).
      Predicted total health care costs were $889 lower with entecavir than with
      adefovir ($91,878 versus $92,768). For incremental cost/life-year gained and
      incremental cost/HCC-free-year gained, entecavir was less costly and more
      effective than adefovir. Sensitivity analyses found the results to be robust to
      plausible variations in health-state costs and discount rate. CONCLUSION: This
      analysis suggests that entecavir improves survival outcomes in a cost-saving
      manner compared with adefovir in CHB patients with hepatic decompensation.

PMID- 22977310
TI  - Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management
      of type 2 diabetes.
AB  - BACKGROUND: The kidney plays an important role in glucose metabolism, and has
      been considered a target for therapeutic intervention. The sodium-glucose
      cotransporter type 2 (SGLT2) mediates most of the glucose reabsorption from the
      proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a
      unique mechanism to lower elevated blood glucose levels in diabetes. The purpose
      of this review is to explore the physiology of SGLT2 and discuss several SGLT2
      inhibitors which have clinical data in patients with type 2 diabetes. METHODS: We
      performed a PubMed search using the terms "SGLT2" and "SGLT2 inhibitor" through
      April 10, 2012. Published articles, press releases, and abstracts presented at
      national and international meetings were considered. RESULTS: SGLT2 inhibitors
      correct a novel pathophysiological defect, have an insulin-independent action,
      are efficacious with glycosylated hemoglobin reduction ranging from 0.5% to 1.5%,
      promote weight loss, have a low incidence of hypoglycemia, complement the action
      of other antidiabetic agents, and can be used at any stage of diabetes. They are
      generally well tolerated. However, due to side effects, such as repeated urinary
      tract and genital infections, increased hematocrit, and decreased blood pressure,
      appropriate patient selection for drug initiation and close monitoring after
      initiation will be important. Results of ongoing clinical studies of the effect
      of SGLT2 inhibitors on diabetic complications and cardiovascular safety are
      crucial to determine the risk-benefit ratio. A recent decision by the Committee
      for Medicinal Products for Human Use of the European Medicines Agency has
      recommended approval of dapagliflozin for the treatment of type 2 diabetes as an
      adjunct to diet and exercise, in combination with other glucose-lowering
      medicinal products, including insulin, and as a monotherapy for metformin
      intolerant patients. Clinical research also remains to be carried out on the long
      term effects of glucosuria and other potential effects of SGLT2 inhibitors,
      especially in view of the observed increase in the incidence of bladder and
      breast cancer. SGLT2 inhibitors represent a promising approach for the treatment
      of diabetes, and could potentially be an addition to existing therapies.

PMID- 22977311
TI  - Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in
      nude mice implanted with cervical cancer.
AB  - PURPOSE: The aim of this study was to examine the effects of the crude extract of
      Acanthus ebracteatus Vahl (AE) on tumor growth and angiogenesis by utilizing a
      tumor model in which nude mice were implanted with cervical cancer cells
      containing human papillomavirus 16 DNA (HPV-16 DNA). MATERIALS AND METHODS: The
      growth-inhibitory effect of AE was investigated in four different cell types:
      CaSki (HPV-16 positive), HeLa (HPV-18 positive), hepatocellular carcinoma cells
      (HepG2), and human dermal fibroblast cells (HDFs). The cell viabilities and
      IC(50) values of AE were determined in cells incubated with AE for different
      lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6-7
      weeks, weighing 20-25 g) were used. A cervical cancer-derived cell line (CaSki)
      with integrated HPV-16 DNA was injected subcutaneously (1 * 10(7) cells/200 MUL)
      in the middle dorsum of each animal (HPV group). One week after injection, mice
      were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day
      for 14 or 28 days (HPV-AE groups). Tumor microvasculature and capillary
      vascularity were determined using laser scanning confocal microscopy. Tumor
      tissue was collected from each mouse to evaluate tumor histology and vascular
      endothelial growth factor (VEGF) immunostaining. RESULTS: The time-response
      curves of AE and the dose-dependent effect of AE on growth inhibition were
      determined. After a 48-hour incubation period, the IC(50) of AE in CaSki was
      discovered to be significantly different from that of HDFs (P < 0.05). A
      microvascular network was observed around the tumor area in the HPV group on days
      21 and 35. Tumor capillary vascularity in the HPV group was significantly
      increased compared with the control group (P < 0.001). High-dose treatment of AE
      extract (HPV-3000AE group) significantly attenuated the increase in VEGF
      expression and tumor angiogenesis in mice that received either the 14- or 28-day
      treatment period (P < 0.001). CONCLUSION: Our novel findings demonstrated that AE
      crude extract could inhibit cervical cancer growth, VEGF expression, and
      angiogenesis in a CaSki-cell transplant model in mice.

PMID- 22977312
TI  - Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and
      urinary symptoms during radiotherapy for prostate carcinoma.
AB  - BACKGROUND: Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere
      with adhesion of bacteria to uroepithelial cells, potentially preventing lower
      urinary tract infections (LUTIs). Because LUTIs are a common side effect of
      external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical
      efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon
      (ecVM) in this condition. METHODS: A total of 370 consecutive patients were
      entered into this study. All patients received intensity-modulated radiotherapy
      for prostate cancer; 184 patients were also treated with ecVM while 186 served as
      controls. Cranberry extract therapy started on the simulation day, at which time
      a bladder catheterization was performed. During EBRT (over 6-7 weeks), all
      patients underwent weekly examination for urinary tract symptoms, including
      regular urine cultures during the treatment period. RESULTS: Compliance was
      excellent, with no adverse effects or allergic reactions being observed, apart
      from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs
      (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were
      recorded. This difference was statistically significant. Furthermore, lower rates
      of nocturia, urgency, micturition frequency, and dysuria were observed in the
      group that received cranberry extract. CONCLUSION: Cranberry extracts have been
      reported to reduce the incidence of LUTIs significantly in women and children.
      Our data extend these results to patients with prostate cancer undergoing
      irradiation to the pelvis, who had a significant reduction in LUTIs compared with
      controls. These results were accompanied by a statistically significant reduction
      in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency),
      suggesting a generally protective effect of cranberry extract on the bladder
      mucosa.

PMID- 22977313
TI  - Positive predictive values of the coding for bisphosphonate therapy among cancer
      patients in the Danish National Patient Registry.
AB  - BACKGROUND: The purpose of this study was to estimate the positive predictive
      value (PPV) of the coding for bisphosphonate treatment in selected cancer
      patients from the Danish National Patient Registry (DNPR). METHODS: Through the
      DNPR, we identified all patients with recorded cancer of the breast, prostate,
      lung, kidney, and with multiple myeloma. We restricted the study sample to
      patients with bisphosphonate treatment recorded during an admission to Aalborg
      Hospital, Denmark, from 2005 through 2009. We retrieved and reviewed medical
      records of these patients from the initial cancer diagnosis onwards to confirm or
      rule out bisphosphonate therapy. We calculated the PPV of the treatment coding as
      the proportion of patients with confirmed bisphosphonate treatment. RESULTS: We
      retrieved and reviewed the medical records of 60 cancer patients with treatment
      codes corresponding to bisphosphonate therapy. Recorded code corresponded to
      treatment administered intravenously for 59 of 60 patients, corresponding to a
      PPV of 98.3% (95% confidence interval 92.5-99.8). In the remaining patient,
      bisphosphonate treatment was also confirmed but was an orally administered
      bisphosphonate; thus, the treatment for any bisphosphonate regardless of
      administration was confirmed for all 60 patients (PPV of 100%, 95% confidence
      interval 95.9-100.0). CONCLUSION: The PPV of bisphosphonate treatment coding
      among cancer patients in the DNPR is very high and the recorded treatment nearly
      always corresponds to intravenous administration.

PMID- 22977314
TI  - Developing a tool to preserve eye contact with patients undergoing colonoscopy
      for pain monitoring.
AB  - Colonoscopy has become the leading procedure for early detection and prevention
      of colorectal cancer. Patients' experience of colonic endoscopic procedures is
      scarcely reported, even though it is considered a major factor in colorectal
      cancer screening participation. Pain due to air inflation or stretching the colon
      with an endoscope is not rare during examination and may be the main obstacle to
      cooperation and participation in a screening program. We propose a four-stage
      study for developing a tool dedicated to pain monitoring during colonoscopy, as
      follows: (1) comparison of patient, nurse, and endoscopist questionnaire
      responses about patient pain and technical details of the procedure using the
      PAINAD tool during colonoscopy; (2) observation of the correlation between
      patients' facial expressions and other parameters (using the short PAINAD); (3)
      development of a device for continuous monitoring of the patient's facial
      expression during the procedure; (4) assessment of the usability of such a tool
      and its contribution to the outcomes of colonoscopy procedures. Early
      intervention by the staff performing the procedure, in reaction to alerts encoded
      by this tool, may prevent adverse events during the procedure.

PMID- 22977315
TI  - Parenting style and practices in stepfamilies.
AB  - There are several studies on the best way to raise a child, ie, what would be the
      consequences of our actions for our children. We tend to think of how to educate
      children in a traditional family, but society has undergone many changes and,
      hence, family structures have undergone changes too. Today, we find a large
      number of stepfamilies facing the same issues concerning how to educate a child.
      Stepfamily configuration often entails more than just the addition of a new
      parent figure. The objective of this study was to shed some light on how these
      stepfamilies deal with issues of parenting style and practices. We reviewed the
      Brazilian and international literature concerning parenting styles and practices
      in stepfamilies. The papers identified were organized and submitted to analysis.
      We identified very few papers addressing parenting styles and practices, pointing
      to an important but unaddressed social change as reflected in new family
      structures. There is a need for longitudinal studies aimed at understanding not
      only a particular moment in time, but also moments within a context, ie, an
      analysis with a holistic approach without preconceived ideas.

PMID- 22977316
TI  - Ethical and legal considerations regarding the ownership and commercial use of
      human biological materials and their derivatives.
AB  - This article considers some of the ethical and legal issues relating to the
      ownership and use - including for commercial purposes - of biological material
      and products derived from humans. The discussion is divided into three parts:
      after first examining the general notion of ownership, it moves to the particular
      case of possible commercial use, and finally reflects on the case in point in the
      light of the preceding considerations. Units of cord blood donated altruistically
      for transplantation and which are found unsuitable for storage and
      transplantation, or which become unsuitable while stored in biobanks, are taken
      as an example. These cord-blood units can be discarded together with other
      biological waste, or they can be used for research or the development of blood
      derived products such as platelet gel. Several ethical questions (eg, informed
      consent, property, distribution of profits, and others) arise from these
      circumstances. In this regard, some criteria and limits to use are proposed.

PMID- 22977317
TI  - Korea's contribution to radiological research included in Science Citation Index
      Expanded, 1986-2010.
AB  - OBJECTIVE: To evaluate scientific papers published by Korean radiologists in the
      Science Citation Index Expanded (SCIE) radiology journals, between 1986 and 2010.
      MATERIALS AND METHODS: The Institute for Scientific Information Web of Knowledge
      Web of Science (SCIE) database was searched for all articles published by Korean
      radiologists, in SCIE radiology journals, between 1986 and 2010. We performed the
      analysis by typing "Korea" and "radiol" in the address section and selecting the
      subject area of "Radiology, Nuclear Medicine, and Medical Imaging" with the use
      of the general search function of the software. Analyzed parameters included the
      total number of publications, document types, journals, and institutions. In
      addition, we analyzed where Korea ranks, compared to other countries, in terms of
      the number of published articles. All these data were analyzed according to five
      time periods: 1986-1990, 1991-1995, 1996-2000, 2001-2005, and 2006-2010. RESULTS:
      Overall, 4974 papers were published by Korean radiologists, in 99 different SCIE
      journals, between 1986 and 2010, of which 4237 (85.2%) were article-type papers.
      Of the total 115395 articles, worldwide, published in radiology journals, Korea's
      share was 3.7%, with an upward trend over time (p < 0.005). The journal with the
      highest number of articles was the American Journal of Roentgenology (n = 565,
      13.3%). The institution which produced the highest number of publications was
      Seoul National University (n = 932, 22.0%). CONCLUSION: The number of scientific
      articles published by Korean radiologists in the SCIE radiology journals has
      increased significantly between 1986 and 2010. Korea was ranked 4th among
      countries contributing to radiology research during the last 5 years.

PMID- 22977318
TI  - Partially cystic thyroid nodules: ultrasound findings of malignancy.
AB  - OBJECTIVE: To seek for the ultrasound (US) findings of partially cystic thyroid
      nodules that are associated with malignancy. MATERIALS AND METHODS: We reviewed
      the US characteristics of 22 surgically confirmed partially cystic papillary
      carcinomas, and compared them with those of 80 benign partially cystic nodules.
      The review cases were selected in a random order from a total of 1029 partially
      cystic nodules that were diagnosed with an US-guided fine needle aspiration
      biopsy over a period of 8 years (June 2003 to October 2010) at our institution.
      RESULTS: In partially cystic thyroid nodules, a taller-than-wide shape (100%, p <
      0.001) and spiculated or microlobulated margin (58.3%, p = 0.003) were
      significantly associated with malignancy. In terms of internal solid portion of
      the nodule, eccentric configuration (68.0%, p < 0.001), non-smooth margin (81.3%,
      p < 0.001), hypoechogenecity (30.0%, p < 0.042), and microcalcification (89.5%, p
      < 0.001) were more frequently demonstrated in malignant nodules than benign ones.
      CONCLUSION: In partially cystic thyroid nodules, understanding the
      characteristics of US findings is important to make a precise diagnosis of
      malignant nodules.

PMID- 22977319
TI  - Trends of CT use in the adult emergency department in a tertiary academic
      hospital of Korea during 2001-2010.
AB  - OBJECTIVE: We wanted to assess the trends of CT examinations that were conducted
      in an adult emergency department (ED). MATERIALS AND METHODS: We searched the
      medical database to identify adult patients (>= 18 years) who had visited the ED
      and the number of CT examinations of the patients during the period from January
      2001 to December 2010. We also analyzed the types of CT scans performed in terms
      of body parts, they were as follows; head CTs, facial bone CTs, neckl CTs, chest
      CTs, abdominal CTs, and miscellaneous CTs. Further, miscellaneous CTs were
      subdivided as CT angiography and others. RESULTS: A total of 113656 CT scans were
      examined for 409439 adult ED patients during a 10-year period, and the number of
      CT scans increased by 255% (from 4743 CTs in 2001 to 16856 CTs in 2010), while
      the adult ED patient volume increased by 34% during the same period. Although the
      head CTs proportionally occupied the most, the facial bone CTs had the largest
      rate of increase (3118%), followed by cervical CTs (1173%), chest CTs (455%),
      miscellaneous CTs (388%; 862% and 84% for CT angiography and others,
      respectively), abdominal CTs (315%) and head CTs (95%) per 1000 patients during
      the decade. CONCLUSION: CT use in adult ED has increased at a rate that far
      exceeds the growth of ED patient volume, with facial bone CTs and cervical CTs
      having the largest increasing rate, followed by chest CTs, miscellaneous CTs,
      abdominal CTs and head CTs.

PMID- 22977321
TI  - Artificial luminal narrowing on contrast-enhanced magnetic resonance angiograms
      on an occasion of stent-assisted coiling of intracranial aneurysm: in vitro
      comparison using two different stents with variable imaging parameters.
AB  - OBJECTIVE: Intracranial stenting for stent-assisted coiling of aneurysms requires
      adequate follow-up imaging. The aim of this in vitro study was to compare in
      stent artificial luminal narrowing on contrast-enhanced MR angiograms (CE-MRA)
      when applying Neuroform(r) and Enterprise(r) stents for stent-assisted coiling.
      MATERIALS AND METHODS: Two intracranial nitinol stents (Enterprise(r) and
      Neuroform(r)) were placed in silicon tubes and then imaged at 3 T and 1.5 T by
      the use of a T1-weighted three-dimensional spoiled gradient-echo sequence with
      minimal TR and TE. CE-MRAs were obtained by using different imaging planes, voxel
      sizes, and bandwidths, and with or without parallel imaging. Artificial lumen
      narrowing (ALN) was calculated and the results were compared. RESULTS: Lower
      magnetic field strength, axial plane perpendicular to axis of stent, and wider
      bandwidth resulted in a lower ALN on CE-MRA for both stents. Larger voxel size
      resulted in lower ALN for Neuroform(r) stent. The parallel imaging acceleration
      factor did not affect ALN. The mean ALN was lower for Neuroform(r), but it was
      not significant by a paired t test. CONCLUSION: CE-MRA of the stented lumen of
      vascular phantom was partially impaired with ALN. Consequently, image plane
      orientation, magnetic field strength, bandwidth, and voxel size should be
      adjusted appropriately to reduce ALN.

PMID- 22977320
TI  - Imaging findings of brain death on 3-tesla MRI.
AB  - OBJECTIVE: To demonstrate the usefulness of 3-tesla (3T) magnetic resonance
      imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging
      (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted
      gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in
      diagnosing brain death. MATERIALS AND METHODS: Magnetic resonance imaging
      findings for 10 patients with clinically verified brain death (group I) and seven
      patients with comatose or stuporous mentality who did not meet the clinical
      criteria of brain death (group II) were retrospectively reviewed. RESULTS:
      Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI
      were highly sensitive and specific findings for the diagnosis of brain death (p <
      0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were
      statistically different between the two groups (p = 0.015, 0.029, and 0.003,
      respectively). However, cortical high signal intensities in T2WI and SWI findings
      were not statistically different between the two group (p = 0.412 and 1.0,
      respectively). CONCLUSION: T2-weighted imaging, DWI, and MRA using 3T MRI may be
      useful for diagnosing brain death. However, SWI findings are not specific due to
      high false positive findings.

PMID- 22977322
TI  - Ventriculus terminalis in adults: unusual magnetic resonance imaging features and
      review of the literature.
AB  - OBJECTIVE: The ventriculus terminalis (VT) in adults is a rare pathology. We
      report various MR imaging features of the adult VT. MATERIALS AND METHODS: Ten
      patients were included in this retrospective review.. All patients had undergone
      magnetic resonance (MR imaging with a surface coil that used two different 1.5T
      MR systems. All patients had undergone initial and follow-up MR imaging with
      contrast enhancement using gadopentate dimeglumine. Three patients underwent
      additional MR imaging using the echocardiogram-gated spatial modulation of
      magnetization (SPAMM) technique. If a shift in tagging band during the systolic
      phase was less than half of the band space, it was defined as a "non-pulsatile
      fluid". Two neuroradiologists independently reviewed these images, while clinical
      symptoms and outcomes were statistically analyzed between the treated and non
      treated group. RESULTS: All cases presented an intramedullary cystic lesion in
      the conus medullaris and showed the same signal intensity as CSF. Three VTs had
      intracystic septation and cord edema, which were pathologically confirmed after
      surgery; two of these were associated with kyphotic deformity and spinal
      arteriovenous malformation. SPAMM-MRI of 3 patients demonstrated non-pulsatile
      fluid motion within the VT. In the treated group, clinical symptoms improved
      better than the non-treated group. CONCLUSION: The adult VT shows some unusual
      imaging features, including septation, cord edema, and coexistence of a spinal
      AVM, as well as the typical findings. Surgical maneuvers may be considered as a
      treatment option in adult VT with progressive neurological symptoms.

PMID- 22977323
TI  - Computer-aided detection of malignant lung nodules on chest radiographs: effect
      on observers' performance.
AB  - OBJECTIVE: To evaluate the effect of computer-aided detection (CAD) system on
      observer performance in the detection of malignant lung nodules on chest
      radiograph. MATERIALS AND METHODS: Two hundred chest radiographs (100 normal and
      100 abnormal with malignant solitary lung nodules) were evaluated. With CT and
      histological confirmation serving as a reference, the mean nodule size was 15.4
      mm (range, 7-20 mm). Five chest radiologists and five radiology residents
      independently interpreted both the original radiographs and CAD output images
      using the sequential testing method. The performances of the observers for the
      detection of malignant nodules with and without CAD were compared using the
      jackknife free-response receiver operating characteristic analysis. RESULTS:
      Fifty-nine nodules were detected by the CAD system with a false positive rate of
      1.9 nodules per case. The detection of malignant lung nodules significantly
      increased from 0.90 to 0.92 for a group of observers, excluding one first-year
      resident (p = 0.04). When lowering the confidence score was not allowed, the
      average figure of merit also increased from 0.90 to 0.91 (p = 0.04) for all
      observers after a CAD review. On average, the sensitivities with and without CAD
      were 87% and 84%, respectively; the false positive rates per case with and
      without CAD were 0.19 and 0.17, respectively. The number of additional
      malignancies detected following true positive CAD marks ranged from zero to seven
      for the various observers. CONCLUSION: The CAD system may help improve observer
      performance in detecting malignant lung nodules on chest radiographs and
      contribute to a decrease in missed lung cancer.

PMID- 22977325
TI  - Fluid collection in the right lateral portion of the superior aortic recess
      mimicking a right mediastinal mass: assessment with chest posterior anterior and
      MDCT.
AB  - OBJECTIVE: We observed patients in whom the fluid collection in the right lateral
      portion of the superior aortic recess on computed tomography (CT) scans mimicked
      a right anterior mediastinal mass on chest PA radiographs. The purpose of this
      study was to assess chest PA and CT features of these patients. MATERIALS AND
      METHODS: All chest PA radiographs and CT scans in 9 patients were reviewed by two
      radiologists on a consensus basis; for the presence of pleural effusion,
      pulmonary edema and heart size on chest PA radiographs. For the portion of the
      fluid collection in the superior aortic recess (SAR), a connection between the
      right lateral portion of the SAR (rSAR) and posterior portion of the SAR (pSAR)
      on CT scans, and the distance between the right lateral margin of the rSAR and
      the right lateral margin of the superior vena cava. RESULTS: Fluid collection in
      the rSAR on CT scans caused a right anterior mediastinal mass or a bulging
      contour on chest PA radiographs in all women patients. All patients showed
      cardiomegaly, five patients had pleural effusion, and two patients had mild
      pulmonary edema. Further, eight patients showed a connection between the rSAR and
      the pSAR. CONCLUSION: The characteristic features of these patients are the right
      anterior mediastinal mass-like opacity due to fluid collection in the rSAR, are
      bulging contour with a smooth margin and cardiomegaly regardless of pulmonary
      edema on the chest PA radiographs, and fluid connection between the rSAR and the
      pSAR on CT scans.

PMID- 22977324
TI  - Anatomy of the sinoatrial nodal branch in Korean population: imaging with MDCT.
AB  - OBJECTIVE: To evaluate, on a retrospective basis, the anatomic characteristics of
      the arterial supply to the sinoatrial node (SAN) in the Korean population using
      an ECG-gated multi-detector CT (MDCT). MATERIALS AND METHODS: The
      electrocardiographic-gated MDCTs of 500 patients (258 men and 242 women; age
      range, 17-83 years; mean age, 58.6 +/- 12.04 years) were analyzed
      retrospectively. In each case, the SAN artery (arteries) was named according to a
      special nomenclature with regard to origin, course, and termination. RESULTS: A
      total of 516 SAN arteries were visualized in 496 patients. The SAN was supplied
      by a single artery in 476 (96.4%) cases and by 2 arteries in 18 (3.6%) cases. The
      SAN originated from the right coronary artery in 265 (53.4%) cases and from the
      left circumflex in 213 (43%) cases. CONCLUSION: This study can provide basic data
      on variations of the SAN artery in the Korean population.

PMID- 22977326
TI  - Histologic characteristics of hepatocellular carcinomas showing atypical
      enhancement patterns on 4-phase MDCT examination.
AB  - OBJECTIVE: To retrospectively define which histologic characteristics of small
      sized hepatocellular carcinomas (HCCs) are related to atypical dynamic
      enhancement on multi-detector computed tomography (MDCT) imaging. MATERIALS AND
      METHODS: Seventy-three patients with 83 HCCs (3 cm or less in diameter) were
      included in this study. All patients underwent 4-phase MDCT imaging and
      subsequent surgery within eight weeks. Two independent radiologists blinded to
      the histologic findings retrospectively classified the HCCs as either typical
      (showing increased enhancement on arterial phase images followed by washout in
      late phase images) or atypical lesions demonstrating any other enhancement
      pattern. From the original pathologic reports, various histologic characteristics
      including gross morphology, nuclear histologic grades, presence of capsule
      formation, and capsule infiltration when a capsule was present, were compared
      among the two groups. RESULTS: An atypical enhancement pattern was seen in 30
      (36.2%) of the 83 HCCs. The mean size of atypical HCCs (1.71 +/- 0.764) was
      significantly smaller than that of typical HCCs (2.31 +/- 0.598, p < 0.001).
      Atypical HCCs were frequently found to be vaguely nodular in gross morphology (n
      = 13, 43.3%) and to have grade I nuclear grades (n = 17, 56.7%). Capsule
      formation was significantly more common in typical HCCs (p < 0.001). Capsular
      infiltration was also more common in typical HCCs (p = 0.001). CONCLUSION: HCCs
      showing atypical dynamic enhancement on MDCT imaging are usually smaller than
      typical HCCs, vaguely nodular type in gross morphology in most cases, and well
      differentiated in nuclear grades, and they lack of capsule formation or capsular
      infiltration.

PMID- 22977327
TI  - Comparison of MRI T2 relaxation changes of knee articular cartilage before and
      after running between young and old amateur athletes.
AB  - OBJECTIVE: To compare changes in T2 relaxation on magnetic resonance (MR) images
      of knee articular cartilage in younger and older amateur athletes before and
      after running. MATERIALS AND METHODS: By using a 3.0-T MR imager, quantitative T2
      maps of weight-bearing femoral and tibial articular cartilages in 10 younger and
      10 older amateur athletes were acquired before, immediately after, and 2 hours
      after 30 minutes of running. Changes in global cartilage T2 signals of the medial
      and lateral condyles of the femur and tibia and regional cartilage T2 signals in
      the medial condyles of femoral and tibia in response to exercise were compared
      between the two age groups. RESULTS: Changes in global cartilage T2 values after
      running did not differ significantly between the age groups. In terms of the
      depth variation, relatively higher T2 values in the older group than in the
      younger group were observed mainly in the superficial layers of the femoral and
      tibial cartilage (p < 0.05). CONCLUSION: Age-related cartilage changes may occur
      mainly in the superficial layer of cartilage where collagen matrix degeneration
      is primarily initiated. However, no trend is observed regarding a global T2
      changes between the younger and older age groups in response to exercise.

PMID- 22977328
TI  - Determination of optimal imaging mode for ultrasonographic detection of subdermal
      contraceptive rods: comparison of spatial compound, conventional, and tissue
      harmonic imaging methods.
AB  - OBJECTIVE: To determine which mode of ultrasonography (US), among the
      conventional, spatial compound, and tissue-harmonic methods, exhibits the best
      performance for the detection of Implanon(r) with respect to generation of
      posterior acoustic shadowing (PAS). MATERIALS AND METHODS: A total of 21
      patients, referred for localization of impalpable Implanon(r), underwent US,
      using the three modes with default settings (i.e., wide focal zone).
      Representative transverse images of the rods, according to each mode for all
      patients, were obtained. The resulting 63 images were reviewed by four observers.
      The observers provided a confidence score for the presence of PAS, using a five
      point scale ranging from 1 (definitely absent) to 5 (definitely present), with
      scores of 4 or 5 for PAS being considered as detection. The average scores of
      PAS, obtained from the three different modes for each observer, were compared
      using one-way repeated measure ANOVA. The detection rates were compared using a
      weighted least square method. RESULTS: Statistically, the tissue harmonic mode
      was significantly superior to the other two modes, when comparing the average
      scores of PAS for all observers (p < 0.00-1). The detection rate was also highest
      for the tissue harmonic mode (p < 0.001). CONCLUSION: Tissue harmonic mode in uS
      appears to be the most suitable in detecting subdermal contraceptive implant
      rods.

PMID- 22977329
TI  - National survey of radiation doses of pediatric chest radiography in Korea:
      analysis of the factors affecting radiation doses.
AB  - OBJECTIVE: To investigate radiation doses in pediatric chest radiography in a
      national survey and to analyze the factors that affect radiation doses. MATERIALS
      AND METHODS: The study was based on the results of 149 chest radiography machines
      in 135 hospitals nationwide. For each machine, a chest radiograph was obtained by
      using a phantom representing a 5-year-old child (ATOM(r) dosimetry phantom, model
      705-D, CIRS, Norfolk, VA, USA) with each hospital's own protocol. Five glass
      dosimeters (M-GD352M, Asahi Techno Glass Corporation, Shizuoka, Japan) were
      horizontally installed at the center of the phantom to measure the dose. Other
      factors including machine's radiography system, presence of dedicated pediatric
      radiography machine, presence of an attending pediatric radiologist, and the use
      of automatic exposure control (AEC) were also evaluated. RESULTS: The average
      protocol for pediatric chest radiography examination in Korea was 94.9 peak
      kilovoltage and 4.30 milliampere second. The mean entrance surface dose (ESD)
      during a single examination was 140.4 microgray (uGy). The third quartile,
      median, minimum and maximum value of ESD were 160.8 uGy, 93.4 uGy, 18.8 uGy, and
      2334.6 uGy, respectively. There was no significant dose difference between
      digital and non-digital radiography systems. The use of AEC significantly reduced
      radiation doses of pediatric chest radiographs (p < 0.001). CONCLUSION: Our
      nationwide survey shows that the third quartile, median, and mean ESD for
      pediatric chest radiograph is 160.8 uGy, 93.4 uGy, and 140.4 uGy, respectively.
      No significant dose difference is noticed between digital and non-digital
      radiography systems, and the use of AEC helps significantly reduce radiation
      doses.

PMID- 22977330
TI  - Uterine artery embolization for symptomatic fibroids with high signal intensity
      on T2-weighted MR imaging.
AB  - OBJECTIVE: To evaluate the effectiveness of uterine artery embolization (UAE) for
      treating symptomatic fibroids with high signal intensity (SI) on magnetic
      resonance (MR) T2-weighted imaging (T2WI). MATERIALS AND METHODS: A total of 537
      cases, consisting of 14 patients with high SI fibroids on T2WI (T2 high group),
      were retrospectively included and compared with 28 randomly selected patients
      with low SI fibroids on T2WI (control group). High SI of a predominant fibroid on
      T2WI was defined as having the same or higher SI than the myometrium. Patient
      ages ranged from 28 to 52 years (mean, 38.1 years). All patients underwent MRI
      before and after UAE. Predominant fibroid and uterine volumes were calculated
      with MR images. Symptom status in terms of menorrhagia and dysmenorrhea was
      scored on a scale of 0-10, with 0 being no symptoms and 10 being the baseline, or
      initial symptoms. RESULTS: Of the patients in the T2 high group, 13 out of 14
      (92.9%) patients demonstrated complete necrosis of the predominant fibroids. The
      mean volume reduction rates of the predominant fibroids in the T2 high group was
      61.7% at three months after UAE, which was significantly higher than the volume
      reduction rates of 42.1% noted in the control group (p < 0.05). Changes in
      symptom scores for menorrhagia and dysmenorrhea after UAE (baseline score minus
      follow-up score) were 4.9 and 7.5 in T2 high group and they were 5.0 and 7.7 in
      control group, suggesting a significant resolution of symptoms (p < 0.01) in both
      groups but no significant difference between the two groups. CONCLUSION: UAE is
      effective for uttering fibroids showing high SI on T2WI. The mean volume
      reduction rate of the predominant fibroids three months after UAE was greater in
      the T2 high group than in the control group.

PMID- 22977332
TI  - Sonographic and CT findings of sialadenosis in a child with leukemia.
AB  - Sialadenosis is characterized by asymptomatic bilateral enlargement of the
      parotid glands. It is uncommon, especially in children. Diagnosis and analysis of
      sialadenosis based on imaging modalities have been rarely reported. Here, we
      report a case of sialadenosis in a child with leukemia, in which the diagnosis
      was made based on sonography and CT findings.

PMID- 22977331
TI  - Radiofrequency ablation of renal tumors: four-year follow-up results in 47
      patients.
AB  - OBJECTIVE: To retrospectively evaluate the intermediate results of radiofrequency
      ablation (RFA) of small renal masses (SRMs). MATERIALS AND METHODS: Percutaneous
      or laparoscopic RFA was performed on 48 renal tumors in 47 patients. The follow
      up studies included a physical examination, chest radiography, creatinine level,
      and contrast-enhanced CT or MRI. To confirm the pathologic criteria of complete
      ablation, 35 patients underwent a follow-up biopsy. Recurrence was defined as
      contrast enhancement on imaging studies after 3 months, lesion growth at
      subsequent imaging, or viable cancer cells on follow-up biopsy. RESULTS:
      Technical success was achieved in 43 (89.6%) of 48 renal tumors. The mean tumor
      size was 2.3 cm and the mean follow-up period was 49.6 months. Repeated RFA was
      necessary in 5 tumors due to incomplete ablation. The overall complication rate
      was 35.8%, of which 96.2% were mild complications. Serum creatinine levels at 12
      months after RFA did not differ from those before RFA (1.28 vs. 1.36 mg/dL). Four
      patients were found to have recurrence at various follow-up intervals, and
      distant metastasis was not found in any cases. CONCLUSION: RFA appears to be a
      useful treatment for selected patients with SRMs. Our 4-year follow-up results
      disclose an excellent therapeutic outcome with RFA, while achieving effective
      local tumor control.

PMID- 22977333
TI  - Mucin-producing carcinoma of the gallbladder: evaluation by magnetic resonance
      cholangiopancreatography in three cases.
AB  - We report three cases of mucin-producing carcinoma of the gallbladder, along with
      the magnetic resonance (MR) findings, especially the findings on a MR
      cholangiopancreatography. In our cases, linear or curvilinear streaks were
      detected running along the long axis of an enlarged gallbladder (mucus thread
      sign). When such findings were seen, a mucin-producing carcinoma of the
      gallbladder should be included as a differential diagnosis. Thus, gadolinium
      enhanced MR imaging is mandatory for the precise diagnosis of the mucin-producing
      carcinoma of the gallbladder.

PMID- 22977334
TI  - Hemorrhagic cardiac tamponade: rare complication of radiofrequency ablation of
      hepatocellular carcinoma.
AB  - Local treatment for hepatocellular carcinoma (HCC) has been widely used in
      clinical practice due to its minimal invasiveness and high rate of cure.
      Percutaneous radiofrequency ablation (RFA) is widely used because its treatment
      effectiveness. However, some serious complications can arise from percutaneous
      RFA. We present here a rare case of hemorrhagic cardiac tamponade secondary to an
      anterior cardiac vein (right marginal vein) injury during RFA for treatment of
      HCC.

PMID- 22977335
TI  - Solid pseudopapillary tumor of the pancreas with hepatic metastasis: spontaneous
      regression over 10-year follow-up period.
AB  - A solid-pseudopapillary tumor (SPT) of the pancreas is known as a low grade
      malignant tumor with a good prognosis; therefore, surgical intervention is
      necessary. A 14-year-old boy presented with a large pancreatic SPT and three
      hepatic metastases. The patient and his family refused surgery. Two serial follow
      up CT scans over a period of 13 years demonstrated almost complete disappearance
      of the pancreatic tumor and three hepatic metastases without relevant treatment.
      Although there have been a few reports of spontaneous healing of SPT, there has
      been no report regarding spontaneous disappearance of SPT and distant metastasis.
      Herein, we report on the spontaneous regression of a large SPT and the
      disappearance of three hepatic metastases.

PMID- 22977336
TI  - Spinal cord glioblastoma induced by radiation therapy of nasopharyngeal
      rhabdomyosarcoma with MRI findings: case report.
AB  - Radiation-induced spinal cord gliomas are extremely rare. Since the first case
      was reported in 1980, only six additional cases have been reported.; The
      radiation-induced gliomas were related to the treatment of Hodgkin's lymphoma,
      thyroid cancer, and medullomyoblastoma, and to multiple chest fluoroscopic
      examinations in pulmonary tuberculosis patient. We report a case of radiation
      induced spinal cord glioblastoma developed in a 17-year-old girl after a 13-year
      latency period following radiotherapy for nasopharyngeal rhabdomyosarcoma. MRI
      findings of our case are described.

PMID- 22977338
TI  - RE: diffusion MR imaging of postoperative bilateral acute ischemic optic
      neuropathy.

PMID- 22977337
TI  - Plasma cell type of Castleman's disease involving renal parenchyma and sinus with
      cardiac tamponade: case report and literature review.
AB  - Castleman's disease is an uncommon disorder characterized by benign proliferation
      of the lymphoid tissue that occurs most commonly in the mediastinum. Although
      unusual locations and manifestations have been reported, involvement of the renal
      parenchyma and sinus, and moreover, manifestations as cardiac tamponade are
      extremely rare. Here, we present a rare case of Castleman's disease in the renal
      parenchyma and sinus that also accompanied cardiac tamponade.

PMID- 22977339
TI  - How to prevent leaving "needle cast" or "cement tail" in vertebroplasty and
      kyphoplasty.

PMID- 22977340
TI  - Redescription of Takahashia citricola Kuwana, 1909, and its transfer to the genus
      Pulvinaria Targioni Tozzetti (Coccoidea, Coccidae).
AB  - The Japanese soft scaleTakahashia citricola Kuwana, 1909 is redescribed and
      transferred to the genus PulvinariaTargioni Tozzettias Pulvinaria citricola
      (Kuwana, 1909), comb. n.(Coccoidea: Coccidae). Pulvinaria gamazumii Kanda, 1960
      is synonymized with Pulvinaria citricolacomb. n. and Pulvinaria nipponica
      Lindinger, 1933, is resurrected as the replacement name for Pulvinaria citricola
      Kuwana, 1914 (nec Kuwana, 1909). The adult female of Pulvinaria citricola
      (Kuwana, 1909) is redescribed and illustrated.

PMID- 22977341
TI  - Molecular phylogeny of the Trechus brucki group, with description of two new
      species from the Pyreneo-Cantabrian area (France, Spain) (Coleoptera, Carabidae,
      Trechinae).
AB  - A molecular phylogeny of the species from the Trechus brucki clade (previously
      Trechus uhagoni group)based on fragments of four mitochondrial genes and one
      nuclear gene is given. We describe Trechus (Trechus) bouillonisp. n. from the
      western pre-Pyrenees: Sierras de Urbasa-Andia, Navarra, Spain. The species was
      collected in mesovoid shallow substratum (mss), a subterranean environment.
      Molecular as well as morphological evidences demonstrate that the new species
      belongs to the Trechus brucki clade. A narrow endemic species of high altitude in
      western French Pyrenees merged with Trechus brucki Fairmaire, 1862a, Trechus
      bruckoidessp. n., is described. A lectotype is designated for Trechus brucki and
      Trechus planiusculus Fairmaire, 1862b (junior synonym of Trechus brucki). The
      species group is redefined based on molecular and morphological characters, and
      renamed as the brucki group, as Trechus brucki was the first described species of
      the clade. A unique synapomorphy of the male genitalia, a characteristic
      secondary sclerotization of the sperm duct, which is shared by all the species of
      the brucki group sensu novo, is described and illustrated. The Trechus brucki
      group sensu novo is composed of Trechus beusti (Schaufuss, 1863), Trechus
      bouillonisp. n., Trechus brucki, Trechus bruckoidessp. n., Trechus grenieri
      Pandelle, 1867, T. uhagoni uhagoni Crotch, 1869, T. uhagoni ruteri Colas, 1935
      and Trechus pieltaini Jeannel, 1920. We discuss the taxonomy of the group and
      provide illustrations of structures showing the differences between the species,
      along with distribution data and biogeographical comments.

PMID- 22977342
TI  - A new species of Fuziidae (Insecta, Blattida) from the Inner Mongolia, China.
AB  - A new species attributed to the genus Parvifuzia Guo & Ren, 2011, Parvifuzia
      peregrinasp. n., is described from the Middle Jurassic Jiulongshan Formation of
      Daohugou Village, Inner Mongolia, China. This new species, with apex of wing
      almost reaching the end of the abdomen and forewing venation with 30-32 veins at
      margin, broadens the diversity of Parvifuzia. This new species, with strongly
      curved cerci, could tightly clasp female and complete copulation more
      efficiently, same as other members of the family Fuziidae.

PMID- 22977343
TI  - The first native Pyrgodesmidae (Diplopoda, Polydesmida) from Australia.
AB  - Three new genera and six new species of Pyrgodesmidae are described from
      Queensland: Asticopyrgodesmusgen. n., containing Asticopyrgodesmus
      lamingtonensissp. n. and Asticopyrgodesmus maialasp. n. (type species);
      Nephopyrgodesmusgen. n., with Nephopyrgodesmus eungellasp. n. (type and only
      species); and Notopyrgodesmusgen. n., with Notopyrgodesmus kullasp. n. (type
      species), Notopyrgodesmus lanosussp. n. and Notopyrgodesmus weirisp. n.
      Localities and specimen data are given in an Appendix for undescribed Australian
      Pyrgodesmidae occurring in wet forests from the Northern Territory south to New
      South Wales, and on Lord Howe Island.

PMID- 22977344
TI  - Australian Assassins, Part III: A review of the Assassin Spiders (Araneae,
      Archaeidae) of tropical north-eastern Queensland.
AB  - The assassin spiders of the family Archaeidae from tropical north-eastern
      Queensland are revised, with eight new species described from rainforest habitats
      of the Wet Tropics bioregion and Mackay-Whitsundays Hinterland: Austrarchaea
      griswoldisp. n., Austrarchaea hoskinisp. n., Austrarchaea karenaesp. n.,
      Austrarchaea tealeisp. n., Austrarchaea thompsonisp. n., Austrarchaea wallaceisp.
      n., Austrarchaea westisp. n. and Austrarchaea woodaesp. n. Specimens of the only
      previously described species, Austrarchaea daviesae Forster & Platnick, 1984, are
      redescribed from the southern Atherton Tableland. The rainforests of tropical
      eastern Queensland are found to be a potential hotspot of archaeid diversity and
      endemism, with the region likely to be home to numerous additional short-range
      endemic taxa. A key to species complements the taxonomy, with maps, natural
      history information and conservation assessments provided for all species.

PMID- 22977345
TI  - Two new apterous species of Lathrobium Gravenhorst (Coleoptera, Staphylinidae,
      Paederinae) from Fujian, East China.
AB  - Two new apterous species of the genus Lathrobium Gravenhorst, 1802 from Fujian
      Province, East China, Lathrobium daocongchaoi Peng & Li, sp. n. and Lathrobium
      fujianense Peng & Li,sp. n., are described and illustrated.

PMID- 22977346
TI  - New species of Vomerina Winterton (Diptera, Therevidae, Agapophytinae) from
      Australia.
AB  - Two new species of Vomerina Winterton, 2007 (Vomerina comapenissp. n. and
      Vomerina micorasp. n.) are described from New South Wales (Australia).

PMID- 22977347
TI  - The apid cuckoo bees of the Cape Verde Islands (Hymenoptera, Apidae).
AB  - The apid cuckoo bees of the Cape Verde Islands (Republic of Cape Verde) are
      reviewed and five species recognized, representing two genera. The ammobatine
      genus Chiasmognathus Engel (Nomadinae: Ammobatini), a specialized lineage of
      cleptoparasites of nomioidine bees is recorded for the first time. Chiasmognathus
      batelkaisp. n. is distinguished from mainland African and Asian species. The
      genus Thyreus Panzer (Apinae: Melectini) is represented by four species - Thyreus
      denoliisp. n., Thyreus batelkaisp. n., Thyreus schwarzisp. n., and Thyreus
      aistleitnerisp. n. Previous records of Thyreus scutellaris (Fabricius) from the
      islands were based on misidentifications.

PMID- 22977348
TI  - Amendment of Articles 8, 9, 10, 21 and 78 of the International Code of Zoological
      Nomenclature to expand and refine methods of publication.
AB  - The International Commission on Zoological Nomenclature has voted in favour of a
      revised version of the amendment to the International Code of Zoological
      Nomenclature that was proposed in 2008. The purpose of the amendment is to expand
      and refine the methods of publication allowed by the Code, particularly in
      relation to electronic publication. The amendment establishes an Official
      Register of Zoological Nomenclature (with ZooBank as its online version), allows
      electronic publication after 2011 under certain conditions, and disallows
      publication on optical discs after 2012. The requirements for electronic
      publications are that the work be registered in ZooBank before it is published,
      that the work itself state the date of publication and contain evidence that
      registration has occurred, and that the ZooBank registration state both the name
      of an electronic archive intended to preserve the work and the ISSN or ISBN
      associated with the work. Registration of new scientific names and nomenclatural
      acts is not required. The Commission has confirmed that ZooBank is ready to
      handle the requirements of the amendment.

PMID- 22977349
TI  - The freshwater snails (Gastropoda) of Iran, with descriptions of two new genera
      and eight new species.
AB  - Using published records and original data from recent field work and revision of
      Iranian material of certain species deposited in the collections of the Natural
      History Museum Basel, the Zoological Museum Berlin, and Natural History Museum
      Vienna, a checklist of the freshwater gastropod fauna of Iran was compiled. This
      checklist contains 73 species from 34 genera and 14 families of freshwater
      snails; 27 of these species (37%) are endemic to Iran. Two new genera, Kaskakia
      and Sarkhia, and eight species, i.e., Bithynia forcarti, Bithynia starmuehlneri,
      Bithynia mazandaranensis, Pseudamnicola georgievi, Kaskakia khorrasanensis,
      Sarkhia sarabensis, Valvata nowsharensis and Acroloxus pseudolacustris are
      described as new to science; Ecrobia grimmi (Clessin & Dybowski, 1888), Heleobia
      dalmatica (Radoman, 1974) and Hippeutis complanatus (Linnaeus, 1758) are reported
      for the first time from Iran. Additional field work is highly desirable for a
      more appropriate evaluation of the extant freshwater snail biodiversity in Iran.

PMID- 22977350
TI  - A new species of Euscorpius Thorell, 1876 (Scorpiones, Euscorpiidae) from Turkey.
AB  - A new species of the genus Euscorpius Thorell, 1876is described based on
      specimens collected from Dilek Peninsula (Davutlar, Aydin) in Turkey. It is
      characterized by an oligotrichous trichobothrial pattern (Pv= 7, et= 5/6, eb= 4)
      and small size. Euscorpius (Euscorpius) avciisp. n. is the first named species of
      the subgenus Euscorpius from Turkey.

PMID- 22977351
TI  - A new Mylabris species from south-eastern Iran and a key to the Iranian species
      of the nominate subgenus (Coleoptera, Meloidae).
AB  - A new species of Mylabris of the nominate subgenus is described and figured. This
      species is apparently endemic to the south-eastern Iranian province of Kerman and
      seems to be phenetically very distinct from all other species of this subgenus,
      primarily because of the unique elytral pattern. A key to the species of the
      nominate subgenus distributed in Iran is also presented.

PMID- 22977352
TI  - First record of Zombrus bicolor (Enderlein) (Hymenoptera, Braconidae, Doryctinae)
      in Western Europe.
AB  - The finding of Zombrus bicolor (Enderlein) (Hymenoptera: Braconidae: Doryctinae)
      in a Tuscan vineyard of the Siena province (Italy) represents the first record of
      this species in western Europe. A female was captured in summer 2009 with a
      malaise trap located in an organic vineyard. Until this finding, the species was
      recorded only in the Oriental regions of continental China, Taiwan, Korea and
      Japan and, very recently, in the eastern and southern parts of the Palaearctic
      region.

PMID- 22977354
TI  - The nonlinear electromigration of analytes into confined spaces.
AB  - We consider the problem of electromigration of a sample ion (analyte) within a
      uniform background electrolyte when the confining channel undergoes a sudden
      contraction. One example of such a situation arises in microfluidics in the
      electrokinetic injection of the analyte into a micro-capillary from a reservoir
      of much larger size. Here, the sample concentration propagates as a wave driven
      by the electric field. The dynamics is governed by the Nerst-Planck-Poisson
      system of equations for ionic transport. A reduced one-dimensional nonlinear
      equation, describing the evolution of the sample concentration, is derived. We
      integrate this equation numerically to obtain the evolution of the wave shape and
      determine how the injected mass depends on the sample concentration in the
      reservoir. It is shown that due to the nonlinear coupling of the ionic
      concentrations and the electric field, the concentration of the injected sample
      could be substantially less than the concentration of the sample in the
      reservoir.

PMID- 22977353
TI  - Mechanostereochemistry and the mechanical bond.
AB  - The chemistry of mechanically interlocked molecules (MIMs), in which two or more
      covalently linked components are held together by mechanical bonds, has led to
      the coining of the term mechanostereochemistry to describe a new field of
      chemistry that embraces many aspects of MIMs, including their syntheses,
      properties, topologies where relevant and functions where operative. During the
      rapid development and emergence of the field, the synthesis of MIMs has witnessed
      the forsaking of the early and grossly inefficient statistical approaches for
      template-directed protocols, aided and abetted by molecular recognition processes
      and the tenets of self-assembly. The resounding success of these synthetic
      protocols, based on templation, has facilitated the design and construction of
      artificial molecular switches and machines, resulting more and more in the
      creation of integrated functional systems. This review highlights (i) the range
      of template-directed synthetic methods being used currently in the preparation of
      MIMs; (ii) the syntheses of topologically complex knots and links in the form of
      stable molecular compounds; and (iii) the incorporation of bistable MIMs into
      many different device settings associated with surfaces, nanoparticles and solid
      state materials in response to the needs of particular applications that are
      perceived to be fair game for mechanostereochemistry.

PMID- 22977355
TI  - Research Activities in Malaysia from the Perspectives of USM Medical School; The
      Reality and the Strategy.

PMID- 22977356
TI  - Cell targeting in anti-cancer gene therapy.
AB  - Gene therapy is a promising approach towards cancer treatment. The main aim of
      the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and
      preserving others. However, its application has been hindered by many factors
      including poor cellular uptake, non-specific cell targeting and undesirable
      interferences with other genes or gene products. A variety of strategies exist to
      improve cellular uptake efficiency of gene-based therapies. This paper highlights
      advancements in gene therapy research and its application in relation to anti
      cancer treatment.

PMID- 22977359
TI  - Dyslipidaemic pattern of patients with type 2 diabetes mellitus.
AB  - The aim of the study was to define dyslipidaemic pattern among type 2 diabetic
      patients using American Diabetes Association guidelines for the classification of
      lipoprotein concentrations into CVD risk categories. The total number screened
      was 211 type 2 diabetic patients who were on treatment between 2001 - 2002 for
      diabetes at the Outpatient Diabetes Clinic in HUSM Kubang Kerian. Fasting venous
      blood samples were analysed for plasma glucose, glycated hemoglobin and serum
      lipids. Type 2 diabetic patients with high, borderline, and low risk LDL
      cholesterol level were 62 %, 25 %, and 10 %, respectively. There were 26 %
      patients in the high risk HDL cholesterol group, 31 % were in the borderline risk
      group, and 43 % were in the low risk group. Only 3 % and 25 % of patients had
      triglycerides concentration in the high and borderline risk categories,
      respectively, but 72 % had low risk triglycerides levels. More female and younger
      subjects than men and older subjects had HDL cholesterol in high and borderline
      risk categories. The percentages of patients with triglycerides values at high
      and borderline high risk category were higher in poor and acceptable glycaemic
      control groups than good glycaemic control group. The most prevalent
      dyslipidaemia pattern was an isolated LDL cholesterol increase, which was
      observed in 35 % of the patients. The second most common pattern of dyslipidaemia
      was a combination of LDL cholesterol above goal with HDL cholesterol below
      target, which was observed in 30 % patients. Patients with established
      dyslipidaemia will require advice regarding diet, exercise and improvement in
      glycaemic control. An active strategy of early detection and drug treatment for
      dyslipidaemia is needed for type 2 diabetic patients.

PMID- 22977358
TI  - What We Know about the Molecular Genetics of Central Nervous System (CNS) Tumours
      in Malaysia.
AB  - The new millennium has been regarded as a genomic era. A lot of researchers and
      pathologists are beginning to understand the scientific basis of molecular
      genetics and relates with the progression of the diseases. Central nervous system
      (CNS) tumours are among the most rapidly fatal of all cancers. It has been
      proposed that the progression of malignant tumours may result from multi-step of
      genetic alterations, including activation of oncogenes, inactivation of tumour
      suppressor genes and also the presence of certain molecular marker such as
      telomerase activity. In this paper, we review some recent data from the
      literature, including our own studies, on the molecular genetics analysis in CNS
      tumours. Our studies have shown that two types of tumour suppressor genes, p53
      and PTEN were involved in the development of these tumours but not in p16 gene
      among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase
      activity also has been detected in various types of CNS tumours. Thus, it is
      important to assemble all data which related to this study and may provide as a
      vital information in a new approach to neuro-oncology studies in Malaysia.

PMID- 22977357
TI  - Anaerobic threshold: its concept and role in endurance sport.
AB  - aerobic to anaerobic transition intensity is one of the most significant
      physiological variable in endurance sports. Scientists have explained the term in
      various ways, like, Lactate Threshold, Ventilatory Anaerobic Threshold, Onset of
      Blood Lactate Accumulation, Onset of Plasma Lactate Accumulation, Heart Rate
      Deflection Point and Maximum Lactate Steady State. But all of these have great
      role both in monitoring training schedule and in determining sports performance.
      Individuals endowed with the possibility to obtain a high oxygen uptake need to
      complement with rigorous training program in order to achieve maximal
      performance. If they engage in endurance events, they must also develop the
      ability to sustain a high fractional utilization of their maximal oxygen uptake
      (%VO(2) max) and become physiologically efficient in performing their activity.
      Anaerobic threshold is highly correlated to the distance running performance as
      compared to maximum aerobic capacity or VO(2) max, because sustaining a high
      fractional utilization of the VO(2) max for a long time delays the metabolic
      acidosis. Training at or little above the anaerobic threshold intensity improves
      both the aerobic capacity and anaerobic threshold level. Anaerobic Threshold can
      also be determined from the speed-heart rate relationship in the field situation,
      without undergoing sophisticated laboratory techniques. However, controversies
      also exist among scientists regarding its role in high performance sports.

PMID- 22977360
TI  - Physical and mental health problems of the elderly in a rural community of
      sepang, selangor.
AB  - The prevalence of aging population is increasing not only in developed countries,
      but also in developing countries like Malaysia. The aim of this study was: (1) to
      determine the prevalence of physical and mental health problems, and (2) to
      determine the association of these health problems with socio demographic factors
      among the elderly in a rural community in Sepang, Selangor. A cross sectional
      study design was used. Five out of nine villages were selected via random
      sampling. The elderly in the selected villages were interviewed using a pre
      tested structured questionnaire which included the GDS-30, ECAQ and Barthel
      Index. Out of 263 elderly residents (6.2% of the total population), 223 agreed to
      participate in the study giving a response rate of 84.8%. The mean age of the
      respondents was 69.7 + 6.8 years with a median of 68 years. The prevalence of
      physical health problems such as chronic illness and functional dependence were
      60.1% and 15.7%, respectively. While the prevalence of mental health problems
      such as depression and cognitive impairment were 7.6% and 22.4%, respectively.
      Among the health problems studied, depression was found to be significantly
      associated with unemployment (p<0.05), where as cognitive impairment was
      significantly associated with age, gender, ethnicity, marital status and level of
      education (p<0.05).

PMID- 22977361
TI  - Correcting Metered-Dose Inhaler Technique vs Switching to Turbohaler in Asthmatic
      Patients a Study on 'Real-Life' Effectiveness.
AB  - In practice, asthmatic patients whose metered-dose inhaler (MDI) technique is
      inefficient are either corrected or changed to dry powder breath-actuated or
      spacer device that is easier to handle. Based on 'real life clinic
      circumstances', we studied 15 symptomatic asthmatic patients whose MDI techniques
      were inefficient that either received correction in their technique (n=9) or were
      changed to turbohaler (n=6). For comparison, we also studied a similar group of
      symptomatic asthmatic patients (n=6) with appropriate MDI techniques that were
      treated by doubling of inhaled corticosteroid (ICS) dose. After 4 weeks, FEV(1)
      and symptom scores in the turbohaler group was significantly improved from
      baseline but not in the corrected MDI group. The group whose ICS dose was doubled
      also showed significant improvement in symptom scores but not in FEV(1). We
      question the benefit gained by correcting MDI technique in some asthmatic
      patients compared to that of switching over to more user-friendly devices such as
      turbohaler. In our study, the improvement observed with turbohaler appears to be
      more than a mere doubling of drug delivery to the lungs and may relate to the
      recognized greater consistency of drug delivery by turbohaler compared to MDI
      device.

PMID- 22977362
TI  - The prevalence of diastolic dysfunction in patients with hypertension referred
      for echocardiographic assessment of left ventricular function.
AB  - Hypertension is the major cause of congestive cardiac failure all over the world.
      It is under diagnosed and achievement of optimal therapy is difficult and costly.
      Diastolic dysfunction is an early poor prognostic factor in hypertension and is a
      reversible condition. Early detection and treatment is necessary to avoid cardiac
      complications. The objective of this study was to assess the occurrence of
      diastolic dysfunction in hypertensive patients referred for echocardiograph
      assessment of left ventricular function in a secondary hospital. It was also
      designed to determine whether contributing factors such as age, gender, systolic
      and diastolic pressure, duration of hypertension, previous myocardial infarct or
      ischemic heart disease and choice of anti-hypertensive drugs influence the
      development of diastolic dysfunction in these hypertensive patients. The analysis
      of diastolic dysfunction was based on the E/A ratio using Doppler echocardiogram.
      All of the patients were recruited from the Echocardiography Unit, Department of
      Medicine, Seremban General Hospital. Fifty patients with history of hypertension
      were selected for the study. Out of These 22 patients (44%) were found to have
      diastolic dysfunction; 39.1% of male patients (9 out of 23) and 48.1% of female
      patients (13 out of 27). Other contributing factors of diastolic dysfunction were
      found in patients : (a) with more than 8 years history of hypertension (12%) (b)
      with history of preexisting IHD/AMI (20%), (c) stages II - III of systolic
      hypertension based on 6th Joint National Committee recommendation (73%) (d) on
      ACE-inhibitor (18%) and (e) on Beta-blocker (28%) In conclusion, the study had
      demonstrated that the duration of hypertension, both systolic and diastolic blood
      pressure and age of patients are important prognostic indicators in predicting
      the development of diastolic dysfunction in hypertensive patients.

PMID- 22977363
TI  - The incidence of post-operative deep vein thrombosis in general surgical patients
      of hospital universiti sains malaysia.
AB  - The incidence of deep vein thrombosis is believed to be rare in Asians. During
      recent years, a few reports have appeared with high incidence in orthopaedic
      patients comparable to Western studies. This study was carried out to find out
      the incidence of post-operative deep vein thrombosis (DVT) after major surgical
      procedures in general surgical patients in an Asian population. In a prospective
      study of 45 consecutive Asian patients after major general surgery, colour-flow
      duplex scan of the legs as an initial screening was done twice within two weeks.
      Mean age of the patients was 54 years 5 months and 87% of patients were included
      in the moderate and high risk group for deep vein thrombosis. Ascending
      venography was used to confirm deep vein thrombosis on patients with equivocal or
      positive results from colour flow duplex scan. One patient showed positive
      evidence of post-operative deep vein thrombosis on colour flow duplex scan which
      was further confirmed by ascending venography; giving an incidence of 2.2%. The
      incidence of post-operative deep vein thrombosis in general surgical patients is
      lower than the Western studies.

PMID- 22977364
TI  - Abdominal cocoon in association with adenomyosis and leiomyomata of the uterus
      and endometriotic cyst : unusual presentation.
AB  - Abdominal cocoon or sclerosing encapsulating peritonitis is a rare condition. A
      46 year old Malay woman with adenomyosis and leiomyomata of the uterus and
      ovarian endometriotic cyst in association with abdominal cocoon is reported.

PMID- 22977365
TI  - Love tragedy, she wrote.
AB  - A case of a 53-year old-single, Kelantanese lady with a diagnosis of paranoid
      schizophrenia for 28 years is reported with aims to illustrate the influence of
      life experiences particularly based on education and intelligent on delusion
      illustrate the evolving nature of the complexity of delusions as well as to show
      the importance of documentation in psychiatric practice. We concluded that this
      patient had used defense mechanism of suppression, reaction formation and
      persecution throughout her delusion. The final persecutory delusion evolved
      through series of transformation via object of admirations. We postulated that in
      depth emotional insight about effects of schizophrenia might have contributed to
      her self-reflection that have made her frustrated with her poor achievement in
      life.

PMID- 22977366
TI  - A case of thyrotoxic hypokalemic paralysis.
AB  - An Indian male patient with acute quadriplegia with hypokalemia as a rare initial
      presentation of thyrotoxicosis is presented in this case report.

PMID- 22977368
TI  - Coping with Brain Disorders using Neurotechnology.
AB  - Brain disorders account for more than 34% of the global burden of disease,
      crippling nations by decreasing their "mental capital"-with greater effect in
      developing countries. Early detection is the key to their management, but
      establishing such programmes seems nearly impossible due to the high prevalence
      of the dysfunctions as compared with the high cost of neuroimaging devices. Thus,
      at first sight, the research of the Decade of the Brain and the international
      Human Brain Mapping Project might seem to be condemned to benefit only a small
      elite. Cuba has shown that is not so by using neurotechnology for the last 3
      decades to implement stratified active screening programmes for brain disorders
      at the population level. This experience has shown that, by the transformation of
      health indicators, an appropriate use of technology can be integrated with
      attention to the population at the primary levels of both health care and
      education. An essential component of neurotechnology is neuroinformatics, which
      like its counterpart bioinformatics-combines databases, analysis tools, and
      theoretical models to craft tools for early disease diagnosis and management.
      Much work remains to be done and will depend critically on south-south
      cooperation to solve problems for countries with similar situations.

PMID- 22977369
TI  - The impact of nutrition education interventions on the dietary habits of college
      students in developed nations: a brief review.
AB  - The purpose of this review is to provide a summary of studies on the
      effectiveness nutrition education interventions used by college students.
      Electronic databases such as Medline, Science Direct, CINAHL (EBSCOhost), and
      Google Scholar were explored for articles that involved nutrition education
      interventions for college students and that were published between 1990 and 2011.
      Fourteen studies, which involved a total of 1668 college students as respondents,
      were identified and met the inclusion criteria. The results showed that there
      were 3 major forms of nutrition education interventions: web-based education,
      lectures, and supplement provisions. Dietary intake measures were used in almost
      all studies and were primarily collected with food records, recall, food
      frequency questionnaires, and dietary habit questionnaires. The outcome measures
      varied among the studies, with indicators such as consumption of food, nutrition
      knowledge, dietary habits, physical activity, and quality of life. Methodological
      issues were also identified. In general, college students experienced significant
      changes in their dietary habits after the interventions were employed. The
      highlighted methodological issues should be considered to improve the quality of
      similar research in future.

PMID- 22977370
TI  - Cloning of a Recombinant Plasmid Encoding Thiol-Specific Antioxidant Antigen
      (TSA) Gene of Leishmania majorand Expression in the Chinese Hamster Ovary Cell
      Line.
AB  - BACKGROUND: TSA (thiol-specific antioxidant antigen) is the immune-dominant
      antigen of Leishmania major and is considered to be the most promising candidate
      molecule for a recombinant or DNA vaccine against leishmaniasis. The aim of the
      present work was to express a plasmid containing the TSA gene in eukaryotic
      cells. METHODS: Genomic DNA was extracted, and the TSA gene was amplified by
      polymerase chain reaction (PCR). The PCR product was cloned into the pTZ57R/T
      vector, followed by subcloning into the eukaryotic expression vector pcDNA3
      (EcoRI and HindIII sites). The recombinant plasmid was characterised by
      restriction digest and PCR. Eukaryotic Chinese hamster ovary cells were
      transfected with the plasmid containing the TSA gene. Expression of the L. major
      TSA gene was confirmed by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and Western blotting. RESULTS: The plasmid containing the TSA
      gene was successfully expressed, as demonstrated by a band of 22.1 kDa on Western
      blots. CONCLUSION: The plasmid containing the TSA gene can be expressed in a
      eukaryotic cell line. Thus, the recombinant plasmid may potentially be used as a
      DNA vaccine in animal models.

PMID- 22977371
TI  - Effect of repeatedly heated palm olein on blood pressure-regulating enzymes
      activity and lipid peroxidation in rats.
AB  - BACKGROUND: Oxidative stress is associated with the pathogenesis of
      cardiovascular diseases. The process of deep-fat frying in dietary cooking oil
      plays a role in the generation of free radicals. In this study, palm olein heated
      to 180  degrees C was tested for its effect on the activity of blood pressure
      regulating enzymes and lipid peroxidation. METHODS: Forty-two adult male Sprague
      Dawley rats were equally assigned into 6 groups.The first group was fed with
      normal rat chow as the control group, and the subsequent groups were fed with rat
      chow fortified with 15% weight/weight of the following: fresh palm olein, palm
      olein heated once, palm olein heated twice, palm olein heated 5 times, or palm
      olein heated 10 times. The duration of feeding was 6 months. Fatty acid analyses
      of oil were performed using gas chromatography. Peroxide values were determined
      using standard titration. Plasma was collected for biochemical analyses. RESULTS:
      Repeatedly heated palm olein increased the levels of peroxide, angiotensin
      converting enzyme, and lipid peroxidation as well as reduced the level of heme
      oxygenase. Fresh palm olein and palm olein heated once had lesser effects on
      lipid peroxidation and a better effect on the activity of blood pressure
      regulating enzymes than repeatedly heated palm olein. CONCLUSION: Repeatedly
      heated palm olein may negatively affect the activity of blood pressure-regulating
      enzymes and increase lipid peroxidation.

PMID- 22977372
TI  - Effect of calabash chalk on the histomorphology of the gastro-oesophageal tract
      of growing wistar rats.
AB  - BACKGROUND: Calabash chalk is a naturally occurring mineral consumed by members
      of some Nigerian communities for pleasure and by pregnant women as a remedy for
      morning sickness. The consumption of this geophagic material motivated our
      interest on the effect of the chalk on the histomorphology of the gastro
      oesophageal tract. METHODS: Twenty-eight young Wistar rats, 4 weeks old, were
      divided into 4 groups of equal size. Group 1 animals served as controls and
      received 1 mL of distilled water. Groups 2, 3, and 4 received orally 1 mL of a
      Calabash chalk suspension containing 40 mg/mL for 14, 21, and 28 days,
      respectively. Upon completion of the treatments, the animals in groups 2, 3, and
      4 were sacrificed on days 15, 22, and 29, respectively, and the control group
      animals were sacrificed on day 29. All animals were euthanised using chloroform
      anaesthesia. The oesophagus and the stomach of each animal were dissected out and
      routinely processed for histological studies. RESULTS: There was oedema with
      haemorrhages in the mucosa of the stomach, and acanthosis, hyperkeratosis, and
      koilocytic changes were observed in the mucosa of the oesophagus of the groups
      treated with 40 mg/mL of Calabash chalk suspension. CONCLUSION: Calabash chalk
      caused histological changes to the stomach and the oesophagus that may lead to
      other pathophysiological conditions.

PMID- 22977373
TI  - Association of mitochondrial DNA 10398 polymorphism in invasive breast cancer in
      malay population of peninsular malaysia.
AB  - BACKGROUND: The mitochondrial DNA (mtDNA) 10398 polymorphism is hypothesised to
      alter a mitochondrial subunit of the electron transfer chain and is associated
      with several neurodegenerative disorders and cancers. METHODS: In this study, an
      mtDNA polymorphism at nucleotide position 10398 was screened in 101 Malay female
      patients with invasive breast cancer and 90 age-matched healthy female controls
      using minisequencing analysis. RESULTS: The Malay women with the 10398G variant
      showed a significantly increased risk of invasive breast cancer (OR = 2.29, 95%
      CI 1.25-4.20, P = 0.007). Immunohistochemistry analysis was conducted to
      investigate the effect of this polymorphism on the levels of apoptosis in breast
      cancer cells. The level of Bax (a pro-apoptotic protein) expression was
      significantly higher than that of Bcl-2 (an anti-apoptotic protein) in patients
      carrying the G allele (P = 0.016) but not in those carrying the A allele (P =
      0.48). CONCLUSION: Based on these findings, we propose that the mtDNA 10398
      polymorphism may be a potential risk marker for breast cancer susceptibility in
      the Malay population.

PMID- 22977374
TI  - Association of the Cocaine- and Amphetamine-Regulated Transcript Prepropeptide
      Gene (CARTPT) rs2239670 Variant with Obesity among Kampar Health Clinic Patrons,
      Malaysia.
AB  - BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART) is a
      hypothalamic anorectic neuropeptide that controls feeding behaviour and body
      weight. The study objective was to investigate the association of the CART
      prepropeptide gene (CARTPT) rs2239670 variant with obesity and its related
      anthropometric indicators among patients of a Malaysian health clinic in Kampar,
      Perak, Malaysia. METHODS: A total of 300 Malay/Peninsular Bumiputera, Chinese,
      and Indian subjects (115 males, 185 females; 163 non-obese, 137 obese) were
      recruited by convenience sampling, and anthropometric measurements, blood
      pressures, and pulse rate were taken. Genotyping was performed using AvaII
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS:
      Genotyping revealed 203 (67.7%), 90 (30.0%), and 7 (2.3%) subjects with the GG,
      GA, and AA genotypes, respectively, with a minor allele (A) frequency of 0.17. No
      significant difference in the CARTPT rs2239670 genotype and allele distribution
      was found between obese and non-obese subjects, and logistic regression showed no
      association between the mutated genotypes (GA, AA) and allele (A) with obesity,
      even after adjusting for age, gender, and ethnicity. Furthermore, the
      measurements did not differ significantly between the genotypes and alleles. No
      significant difference in the genotype and allele distribution was found among
      genders, but they were significantly different among ethnicities (P = 0.030 and P
      = 0.019, respectively). CONCLUSION: CARTPT rs2239670 is not a predictor for
      obesity among the Malaysian subjects in this study.

PMID- 22977375
TI  - Comparison of Image Quality Criteria between Digital Storage Phosphor Plate in
      Mammography and Full-Field Digital Mammography in the Detection of Breast Cancer.
AB  - BACKGROUND: Digital mammography is slowly replacing screen film mammography. In
      digital mammography, 2 methods are available in acquiring images: digital storage
      phosphor plate and full-field digital mammography. The aim of this study was to
      compare the image quality acquired from the 2 methods of digital mammography in
      the detection of breast cancer. METHODS: The study took place at the National
      Cancer Society, Kuala Lumpur, and followed 150 asymptomatic women for the
      duration of 1 year. Participating women gave informed consent and were exposed to
      4 views from each system. Two radiologists independently evaluated the printed
      images based on the image quality criteria in mammography. McNemar's test was
      used to compare the image quality criteria between the systems. RESULTS: The
      agreement between the radiologists for the digital storage phosphor plate was k =
      0.551 and for full-field digital mammography was k = 0.523. Full-field digital
      mammography was significantly better compared with the digital storage phosphor
      plate in right and left mediolateral oblique views (P < 0.05) in the detection of
      microcalcifications, which are early signs of breast cancer. However, both
      systems were comparable in all other aspects of image quality. CONCLUSION:
      Digital mammography is a useful screening tool for the detection of early breast
      cancer and ensures better prognosis and quality of life.

PMID- 22977376
TI  - Assessment of Prospective Physician Characteristics by SWOT Analysis.
AB  - BACKGROUND: Thailand is one of the developing countries encountering medical
      workforce shortage. From the national registry in 2006, there were 33 166
      physicians: 41.5% worked in the government sector, 21.6% worked in the private
      sector, and the remaining worked in non-medical fields. There is no current data
      to confirm the effectiveness of the national policy to increase physician
      production. We demonstrate our findings from the strength, weakness, opportunity,
      and threat (SWOT) analysis in medical students and the potential impact on
      national workforce planning. METHODS: We introduced SWOT analysis to 568 medical
      students during the 2008-2010 academic years, with the objective of becoming "a
      good physician in the future". RESULTS: Pertinent issues were grouped into 4
      categories: not wanting to be a doctor, having inadequate medical professional
      skills, not wanting to work in rural or community areas, and planning to pursue
      training in specialties with high salary/low workload/low risk for lawsuit. The
      percentages of medical students who described themselves as "do not want to be a
      doctor" and "do not want to work in rural or community areas" increased from
      7.07% and 25.00% in 2008 to 12.56% and 29.65% in 2010, respectively. CONCLUSION:
      Further intervention should be considered in order to change the medical students
      attitudes on the profession and their impact on Thai health system.

PMID- 22977377
TI  - Pheochromocytoma and pregnancy: a difficult and dangerous ordeal.
AB  - Pheochromocytoma during pregnancy is potentially disastrous to the mother and
      fetus. Its ambiguous presentation is often mistaken for pre-eclampsia, although
      it may imitate other problems during pregnancy. Early diagnosis and timely,
      appropriate management reduces possible maternal and fetal complications. We
      identified a case of pheochromocytoma during pregnancy; the condition was
      initially diagnosed as pre-eclampsia complicated with gestational diabetes.
      Surgical intervention via left adrenalectomy was successfully performed in the
      second trimester. After surgery, all of the patient's medical problems nearly
      subsided and she did not require further treatment. However, her fetus displayed
      restricted intrauterine growth, and the patient eventually had premature delivery
      via a caesarean section. A multidisciplinary team to identify and treat
      pheochromocytoma is mandatory to ensure optimal conditions for tumour removal and
      to anticipate any possible catastrophic events.

PMID- 22977378
TI  - Two different surgical approaches for strangulated obturator hernias.
AB  - Obturator hernia is a rare condition that may present in an acute or subacute
      setting in correlation with the degree of small-bowel obstruction. Pre-operative
      diagnosis is difficult, as symptoms are often non-specific. A high index of
      suspicion should be maintained for emaciated elderly women with small-bowel
      obstruction without a previous abdominal operation and a positive Howship-Romberg
      sign. When diagnosis is in doubt, computed tomography scan of the abdomen and the
      pelvis (if available) or laparotomy should be performed immediately, as high
      mortality rate is related to the perforation of gangrenous bowels. We present 2
      cases of strangulated obturator hernia, managed differently with both open and
      laparoscopic approaches. The diagnostic accuracy of computed tomography scan is
      highlighted followed by a brief literature review with an emphasis placed on
      surgical management.

PMID- 22977379
TI  - Management of spontaneous perforation of the bile duct in an infant in a semi
      urban setup: a case report.
AB  - Spontaneous perforation of the extrahepatic bile duct leading to biliary
      peritonitis is a rare occurrence once other causes of biliary peritonitis, such
      as trauma, choledochal cyst, stone diseases, and distal atresia of the bile duct,
      are ruled out. A 7-month-old male infant was brought to the hospital in critical
      condition with distension of the abdomen. He had a history of vomiting and
      diarrhoea, low-grade fever, and refusal to feed for 2 days. Signs of peritonitis
      were found upon examination. Due to the poor general condition of the patient,
      the case was taken up for laparotomy, and a diagnosis of spontaneous extrahepatic
      bile duct perforation was made intra-operatively. In the present case, the cause
      was idiopathic. An external drain was placed near the site of the leak for 2
      weeks. The patient recovered well and was discharged on post-operative day 16.
      Disease awareness for correct pre-operative diagnosis and interventional planning
      is required to reduce mortality, morbidity, and complications in spontaneous
      perforation of the common bile duct.

PMID- 22977380
TI  - Gastric duplication cyst in an infant presenting with non-bilious vomiting.
AB  - In an infant presenting with a mass in the abdomen and non-bilious vomiting,
      duplication cyst needs to be considered in the list of differential diagnoses.
      Gastric duplication cyst is an uncommon occurrence in children. Diagnosis is
      based on clinical findings and imaging features. Surgical excision is safe and
      offers a complete cure. The literature recommends excision even in asymptomatic
      cases due to isolated reports of malignancy arising in the duplication cyst in
      later life.

PMID- 22977381
TI  - Letter to The Editor: Evaluation of Glucose and Energy Expenditure in the Acute
      Care of Severe Head Injury Patients: Indirect Calorimeter versus Harris Benedict
      Formula.

PMID- 22977382
TI  - Beyond medical school - time to re-look?

PMID- 22977383
TI  - New advances in the diagnosis of typhoid and detection of typhoid carriers.
AB  - For effective management of typhoid, diagnosis of the disease must be done with
      speed and accuracy. Development of such a test would require antigens that are
      specific for typhoid diagnosis. Attempts at finding the specific antigen have
      been carried out throughout the years. The finding of such an antigen can lead to
      carrier detection as well. Candidate antigens have been used in the development
      of antigen or antibody detection tests with variation in sensitivity and
      specificity. Further characterization and understanding of the candidate antigens
      combined with use of innovative technologies will allow for the ideal test for
      typhoid and typhoid carriers to be within reach.

PMID- 22977384
TI  - Anticipated difficulties in house-officership for graduating medical students of
      the school of medical sciences, universiti sains malaysia kubang kerian,
      kelantan, malaysia.
AB  - To aid future curriculum revision and planning, a batch of newly graduated
      medical students were surveyed using a questionnaire containing items
      representing possible areas of concern during house-officership. Students rated
      items representing communication issues as areas of concern. They did not agree
      that areas concerning responsibilities as a doctor, continuing medical education,
      theoretical and practical skills and potentially stressful working conditions
      were problem areas. Communication skills should remain among the priority areas
      for undergraduate training. Students should also be given more information about
      the house-officership period prior to graduation. Further study is needed to
      confirm perceived strengths of the USM curriculum suggested by the study, which
      are skills in finding resources for further learning and skills in leadership. A
      task-analysis of the house-officership period is also needed.

PMID- 22977385
TI  - Work-related musculoskeletal symptoms among batik workers in kelantan.
AB  - A cross sectional study was carried out to evaluate the extent of occupational
      health problems focusing on some aspects of musculoskeletal symptoms among batik
      workers in Kelantan, Malaysia. The workers selected must have been in that
      industry for at least one year. Using cluster sampling, 202 workers were selected
      from 21 factories. More than half (60.2%) of the workers had been troubled with
      musculoskeletal symptoms at work. The most common symptoms were pain over the
      shoulders (41.0%), lower back (34.4%) and ankle (34.4%). Duration of employment,
      younger age group, prolonged standing and awkward working task were among
      contributing factors. It is therefore necessary to improve on both ergonomic and
      psychosocial environments of batik workers in order to prevent these
      musculoskeletal symptoms.

PMID- 22977386
TI  - The effect of induced visual stress on three dimensional perception.
AB  - Previous studies have shown that stress on the vergence and accommodation
      systems, either artificially induced or naturally occurring, results in small
      misalignment of the visual axes, reduces binocular visual acuity and produces
      symptoms of ocular discomfort. This study examines the effect of artificially
      induced visual stress using ophthalmic prisms on three dimensional perception on
      30 optometry students ages ranging from 19 to 29 years old. 6D base-in prisms,
      equally divided between the eyes (3D base-in each) was used to induce stress on
      the visual system producing misalignment of visual axes known as fixation
      disparity. The fixation disparity is quantified using near vision Mallett Unit
      and an enlarged scaled diagram. Stereoscopic perception was measured with the TNO
      test, with and without the presence of stress and the results was compared.
      Wilcoxon's matched pair ranked tests show statistically significant difference in
      the stereo thresholds of both conditions, p = 0.01 for advancing stereopsis and p
      = 0.01 for receding stereopsis, respectively. The study concludes that visual
      stress induced by prisms, produce misalignment of the visual axes and thus
      reduces three dimensional performance.

PMID- 22977387
TI  - Detection of human papillomavirus using in situ hybridization technique in vulvo
      vaginal warts.
AB  - Human papillomavirus (HPV) is the commonest sexually transmitted viral infection
      and one of its manifestations is genital warts or condyloma acuminata. Eight
      cases of vulvo-vaginal warts were diagnosed between January 1992 and December
      1993. There were 4 Malays, 2 Chinese and 2 Indians. The patients' age ranged from
      22 to 43 years (mean 27.9 years). Formalin-fixed, paraffin-embedded tissues were
      studied by histology and in situ hybridization using biotinylated probes to
      detect the HPV deoxyribonucleic acid (DNA) of types 6, 11, 16, 18, 31 and 33. All
      vulvar and vaginal lesions showed typical histopathological features of
      condylomatous changes. HPV 6 and HPV 11 were detected in 100% (8/8) and 87.5%
      (7/8) of all cases, respectively. HPVs 16, 18, 31 and 33 were not found. The
      positive cells were mainly in the upper layers of the squamous epithelium. The
      hybridization data indicated that the HPV found in this study one of the same
      types as found in other studies.

PMID- 22977388
TI  - Biventricular central neurocytoma.
AB  - A case of biventricular neurocytoma is reported. A 36 year old Malay lady
      presented with headache of 8 months duration. Physical examination revealed signs
      of increase intracranial pressure. CT-scan and MRI showed tumour in both lateral
      ventricles. Patient underwent tumour debulking followed by adjuvant radiotherapy.
      The radiological appearances of central neurocytoma are discussed.

PMID- 22977389
TI  - The triad of lichen planus, thymoma and liver cirrhosis-hepatoma. First reported
      case.
AB  - We describe a patient with liver cirrhosis who presented with erosive oral and
      cutaneous lichen planus (LP) and incidentally was found simultaneously to have
      thymoma and hepatoma. We support the notion forwarded earlier that LP and chronic
      liver disease is more than a mere coincidence and that there is a non
      coincidental association between LP and thymoma. We believe this is also the
      first reported case in the English Literature of coexistence of the three
      condition LP, thymoma and hepatoma complicating liver disease.

PMID- 22977390
TI  - Cerebellar hemangioblastoma in a patient with von hippel-lindau disease : a case
      report.
AB  - A 23 year-old Chinese woman presented with symptoms of increased intracranial
      pressure due to obstructive hydrocephalus as a sequel to a mass effect from
      cerebellar haemangioblastoma. She underwent removal of the right cerebellar
      haemangioblastoma and ventriculo-peritoneal shunting. She also had bilateral
      retinal haemangioblastoma, left renal carcinoma, renal and pancreatic cysts
      without phaeochromocytoma. A left partial nephrectomy was performed for renal
      cell carcinoma followed by radiotherapy. She survived the initial episode only to
      succumb to another cerebellar haemorrhage 18 months later.

PMID- 22977391
TI  - Programs to manage aggressive behaviour in long-term care patients: a review of
      clinical effectiveness, cost-effectiveness, and guidelines.

PMID- 22977392
TI  - Dialectical behaviour therapy in adolescents for suicide prevention: systematic
      review of clinical-effectiveness.

PMID- 22977393
TI  - Drugs for pulmonary arterial hypertension: a systematic review of the clinical
      effectiveness of combination therapy.

PMID- 22977394
TI  - Octaplas compared with fresh frozen plasma to reduce the risk of transmitting
      lipid-enveloped viruses: an economic analysis and budget impact analysis.

PMID- 22977395
TI  - Oral appliances for treatment of snoring and obstructive sleep apnea: a review of
      clinical effectiveness.

PMID- 22977396
TI  - Diagnosis of snoring and obstructive sleep apnea: a review of the accuracy.

PMID- 22977397
TI  - Rapid-Acting Insulin Analogues for the Treatment of Diabetes Mellitus: Meta
      analyses of Clinical Outcomes.

PMID- 22977398
TI  - Long-Acting Insulin Analogues for the Treatment of Diabetes Mellitus: Meta
      analyses of Clinical Outcomes.

PMID- 22977399
TI  - Systematic review of use of blood glucose test strips for the management of
      diabetes mellitus.

PMID- 22977400
TI  - Cost-effectiveness of blood glucose test strips in the management of adult
      patients with diabetes mellitus.

PMID- 22977401
TI  - Optimal therapy recommendations for the prescribing and use of blood glucose test
      strips.

PMID- 22977402
TI  - Dabigatran or rivaroxaban versus other anticoagulants for thromboprophylaxis
      after major orthopedic surgery: systematic review of comparative clinical
      effectiveness and safety.

PMID- 22977403
TI  - Vasopressin as first-line therapy for cardiac arrest: a review of the guidelines
      and clinical-effectiveness.

PMID- 22977404
TI  - Pre-Operative Screening for Methicillin-Resistant Staphylococcus aureus (MRSA)
      Infection: A Review of the Clinical-Effectiveness and Guidelines.

PMID- 22977405
TI  - Endobronchial ultrasound for lung cancer diagnosis and staging: a review of the
      clinical and cost-effectiveness.

PMID- 22977406
TI  - Technologies to reduce errors in dispensing and administration of medication in
      hospitals: clinical and economic analyses.

PMID- 22977407
TI  - Fecal immunochemical tests for colorectal cancer screening: a systematic review
      of accuracy and compliance.

PMID- 22977408
TI  - Foot care for patients with peripheral vascular disease: a review of the
      guidelines.

PMID- 22977409
TI  - TomoTherapy, Gamma Knife, and CyberKnife Therapies for Patients with Tumours of
      the Lung, Central Nervous System, or Intra-abdomen: A Systematic Review of
      Clinical Effectiveness and Cost-Effectiveness.

PMID- 22977411
TI  - Clopidogrel versus Other Antiplatelet Agents in the Secondary Prevention of
      Vascular Events in Adults with Cerebrovascular Disease: Clinical and Cost
      Effectiveness Analyses.

PMID- 22977412
TI  - H1N1 and Seasonal Influenza Vaccine Practices across Canadian Jurisdictions.

PMID- 22977410
TI  - Long-acting beta(2)-agonist and inhaled corticosteroid combination therapy for
      adult persistent asthma: systematic review of clinical outcomes and economic
      evaluation.

PMID- 22977413
TI  - Portable monitoring devices for diagnosis of obstructive sleep apnea at home:
      review of accuracy, cost-effectiveness, guidelines, and coverage in Canada.

PMID- 22977414
TI  - Cognitive behavioural therapy for post-traumatic stress disorder: a review of the
      clinical and cost-effectiveness.

PMID- 22977415
TI  - Self-directed cognitive behavioural therapy for adults with diagnosis of
      depression: systematic review of clinical effectiveness, cost-effectiveness, and
      guidelines.

PMID- 22977416
TI  - Cognitive behavioural therapy for patients with addictions: a review of the
      clinical and cost-effectiveness.

PMID- 22977417
TI  - Pulmonary rehabilitation for chronic obstructive pulmonary disease: clinical,
      economic, and budget impact analysis.

PMID- 22977418
TI  - Positron Emission Tomography (PET) in Oncology: A Systematic Review of Clinical
      Effectiveness and Indications for Use.

PMID- 22977419
TI  - Triple Therapy for Moderate-to-Severe Chronic Obstructive Pulmonary Disease.

PMID- 22977420
TI  - Letter in response to the Article published by Reich O, Rapold R, Flatscher-Thoni
      M. An empirical investigation of the efficiency effects of integrated care models
      in Switzerland. Int J Integr Care 2012,12:1-12.

PMID- 22977421
TI  - 'Continuity of care': a critical interpretive synthesis of how the concept was
      elaborated by a national research programme.
AB  - INTRODUCTION: A Continuity of Care Research Programme was undertaken in England
      in 2000-9. The Programme was informed by a conceptual framework proposed by
      Freeman and colleagues in an earlier scoping study. At the end of the Programme,
      a conceptual synthesis was carried out in order to confirm or refine the 'Freeman
      model' of continuity of care. METHODS: A conceptual synthesis of the outputs of
      the Programme, using Critical Interpretive Synthesis. RESULTS: The conceptual
      framework underpinning the Freeman model of continuity of care, which prioritises
      the perspectives of service users and carers, was variously utilised in the
      Programme. Analysis revealed indications of an emerging shift from the patient
      and carer 'perspectivist' paradigm of the Freeman model towards a new
      'partnership' paradigm where continuity is recognised to be co-constructed by
      patients, families and professionals, all of whom have an active part to play in
      its accomplishment. CONCLUSIONS: The projects in the Programme have advanced
      understanding of patients' perspectives on continuity of care and on the complex
      nature of this concept. At the same time, they have raised issues and reported
      findings which may be indicative of an emergent paradigm shift in this area of
      research, towards a more dynamic partnership model.

PMID- 22977422
TI  - Towards a better integrated stroke care: the development of integrated stroke
      care in the southern part of the Netherlands during the last 15 years (Special
      10th Anniversary Edition paper).
AB  - INTRODUCTION: Stroke care is complex and often provided by various healthcare
      organisations. Integrated care solutions are needed to optimise stroke care. In
      this paper, we describe the development of integrated stroke care in the region
      of Maastricht during the last 15 years. DESCRIPTION OF INTEGRATED CARE CASE:
      Located in the south of the Netherlands, the region of Maastricht developed
      integrated stroke care to serve a population of about 180,000 people. Integration
      was needed to improve the continuity, coordination and quality of stroke care.
      The development of integrated care in Maastricht was a phased process. The last
      phase emphasized early discharge from hospital and assessing the best individual
      rehabilitation track in a specialized nursing home setting. DISCUSSION AND
      LESSONS LEARNED: The development and implementation of integrated stroke care in
      the region of Maastricht led to fewer days in hospital, more patients being
      directly admitted to the stroke unit and an earlier start of rehabilitation. The
      implementation of early discharge from the hospital and rehabilitation assessment
      in a nursing home led to some unforeseen problems and lessons learned.

PMID- 22977423
TI  - Competition and integration in health care reform.
AB  - There is a growing but still fragile understanding that competition and
      integration are not necessarily in conflict and can be used together. In one
      version, this might mean using competition to drive improvements in performance
      in planned care, and promoting integration to do so in relation to unplanned care
      and care for people with complex needs. In another, it entails arguing that
      competition between integrated systems might offer the best of all worlds, if
      policies can be designed to support evolution in that direction. This paper
      suggests that a bundle of policy interventions is needed to support the evolution
      of integrated systems of care. It examines how policies might be crafted to make
      this happen; How to avoid the wrong kind of integration to develop; and, how can
      policy-makers enable competition between integrated systems.

PMID- 22977424
TI  - Study protocol-an exploratory trial on health promoting schools at Dutch
      secondary schools.
AB  - BACKGROUND: Recent studies show adolescent health-related behaviours to co-occur
      synergistically. This paper describes the study design for an exploratory trial
      on the effects of a comprehensive, whole-school health promoting school
      intervention. This intervention tackles seven different behavioural domains
      simultaneously via a combination of education, creating a healthy environment and
      introducing healthy behavioural policies. Additionally, extensive partnerships
      are formed between schools, parents, neighbourhoods and youth health authorities
      to coordinate health promotion efforts. STUDY DESIGN AND DATA COLLECTION METHODS:
      The intervention will be implemented at two secondary schools. Results will be
      compared with two control schools (n~1500). The intervention's effectiveness in
      changing student behaviours as well as physical and psychosocial health status
      along with qualitative lessons learned on the integration of youth health care
      services and school health education practices are the main aimed outcomes of
      this study. Data are collected via a mixed methods design combining an annual
      youth health (behaviour) monitor with a qualitative process evaluation via
      interviews with key stakeholders. DATA ANALYSIS: A multilevel analysis is
      performed combined with a systematic analysis of qualitative interview data.
      CONCLUSIONS: This study will produce an evaluation of a comprehensive health
      promoting school intervention that combines an integrated approach of schools,
      neighbourhoods, families and youth health services to improve adolescent health.

PMID- 22977425
TI  - Progress with relationship continuity 2012, a British perspective.
AB  - This perspective paper makes a brief conceptual review of continuity and argues
      that relationship continuity is the most controversial type. Plentiful evidence
      of association with better satisfaction and outcomes urgently needs to be
      supplemented by studies of causation. The scope of these has been outlined in
      this paper. Evidence strongly suggests that patients generally want more
      relationship continuity than they are getting and that relationship continuity is
      linked with better patient and staff satisfaction. This is reason enough to
      justify improving relationship continuity for patients.

PMID- 22977426
TI  - Integrated transitional care: patient, informal caregiver and health care
      provider perspectives on care transitions for older persons with hip fracture.
AB  - INTRODUCTION: Complex older adults, such as those with hip fracture, frequently
      require care from multiple professionals across a variety of settings. Integrated
      care both between providers and across settings is important to ensure care
      quality and patient safety. The purpose of this study was to determine the core
      factors related to poorly integrated care when hip fracture patients transition
      between care settings. METHODS: A qualitative, focused ethnographic approach was
      used to guide data collection and analysis. Patients, their informal caregivers
      and health care providers were interviewed and observed at each care transition.
      A total of 45 individual interviews were conducted. Interview transcripts and
      field notes were coded and analysed to uncover emerging themes in the data.
      RESULTS: FOUR FACTORS RELATED TO POORLY INTEGRATED TRANSITIONAL CARE WERE
      IDENTIFIED: confusion with communication about care, unclear roles and
      responsibilities, diluted personal ownership over care, and role strain due to
      system constraints. CONCLUSIONS: Our research supports a broader notion of
      collaborative practice that extends beyond specific care settings and includes an
      appropriate, informed role for patients and informal caregivers. This research
      can help guide system-level and setting-specific interventions designed to
      promote high-quality, patient-centred care during care transitions.

PMID- 22977427
TI  - Management continuity in local health networks.
AB  - INTRODUCTION: Patients increasingly receive care from multiple providers in a
      variety of settings. They expect management continuity that crosses boundaries
      and bridges gaps in the healthcare system. To our knowledge, little research has
      been done to assess coordination across organizational and professional
      boundaries from the patients' perspective. Our objective was to assess whether
      greater local health network integration is associated with management continuity
      as perceived by patients. METHOD: We used the data from a research project on the
      development and validation of a generic and comprehensive continuity measurement
      instrument that can be applied to a variety of patient conditions and settings.
      We used the results of a cross-sectional survey conducted in 2009 with 256
      patients in two local health networks in Quebec, Canada. We compared four aspects
      of management continuity between two contrasting network types (highly integrated
      vs. poorly integrated). RESULTS: The scores obtained in the highly integrated
      network are better than those of the poorly integrated network on all dimensions
      of management continuity (coordinator role, role clarity and coordination between
      clinics, and information gaps between providers) except for experience of care
      plan. CONCLUSION: Some aspects of care coordination among professionals and
      organizations are noticed by patients and may be valid indicators to assess care
      coordination.

PMID- 22977428
TI  - "It is a good idea, but..." A qualitative study of implementation of 'Individual
      Plan' in Norwegian mental health care.
AB  - AIM OF THE STUDY: The aim of the study is to explore and describe what hampers
      and promotes the implementation of 'Individual Plan'-Norway's answer to
      integrated care, and to discuss the findings according to implementation theory
      and research. BACKGROUND: 'Individual Plan' is a master-plan intended to increase
      user-participation and provide better coordination of measures for patients in
      need of extensive and long-term health-care services. Norwegian Health
      Authorities used a dissemination strategy to implement 'Individual Plan' but
      managers within health and social care could choose their own way of
      implementation in their organisation. METHODOLOGY: Twenty-two managers from
      different clinics and organisational levels within mental health care were
      interviewed with an in-depth semi-structured interview about the implementation
      process in their organisation. The analysis was primarily made according to
      systematic text condensation. FINDINGS: The findings describe different
      implementation processes and how the managers identified with the usefulness of
      'Individual Plan' as a tool, choice of practical implementation strategies, the
      manager's own role, characteristics of organisational culture as well as how the
      manager considered external factors such as administration, lack of time and
      resources. The evolved implementation themes are discussed within a frame of
      existing knowledge and theory. CONCLUSION: A complex picture of barriers,
      dilemmas and benefits emerges, both internal and external to an organisation as
      well as at a personal level that need to be taken into consideration in
      forthcoming implementation processes to increase the rate of success.

PMID- 22977430
TI  - Lost in transition 2.0: a long days' journey towards continuity of care.

PMID- 22977429
TI  - Integrated care in Germany-a stony but necessary road!
AB  - German healthcare provides a very comprehensive benefits catalogue, high quality
      standards, low access barriers and in particular healthcare which is independent
      from one's income. But at the same time it is one of the most expensive systems
      in the world. Reasons for the high costs of care are mainly due to the separation
      of the outpatient, inpatient and rehabilitation sectors, the poor information
      flow between the service providers and insufficient competition in healthcare
      provision. In the last 15 years the German government has introduced various
      reform acts and in doing so has followed a continual path of development: more
      competition for care concepts between health insurances, more options for the
      insured and more leeway for players in the various sectors of healthcare. The
      following article gives an overview of new forms of contracting that have been
      introduced and provides recommendations for the further development of integrated
      care in the German healthcare system.

PMID- 22977431
TI  - Care delivery pathways for Chronic Obstructive Pulmonary Disease in England and
      the Netherlands: a comparative study.
AB  - INTRODUCTION: A remarkable difference in care delivery pathways for Chronic
      Obstructive Pulmonary Disease (COPD) is the presence of hospital-at-home for COPD
      exacerbations in England and its absence in the Netherlands. The objective of
      this paper is to explain this difference. METHODS: Descriptive COPD statistics
      and care delivery pathways on all care levels within the institutional context,
      followed by a comparison of care delivery pathways and an explanation of the
      difference with regard to hospital-at-home. RESULTS: The Netherlands and England
      show broad similarities in their care delivery pathways for COPD patients. A
      major difference is the presence of hospital-at-home for COPD exacerbations in
      England and its absence in the Netherlands. Three possible explanations for this
      difference are presented: differences in the urgency for alternatives (higher
      urgency for alternative treatment models in England), the differences in funding
      (funding in England facilitated the development of hospital-at-home) and the
      differences in the substitution of tasks to nurses (substitution to nurses has
      taken place to a larger extent in England). DISCUSSION AND CONCLUSION: The
      difference between the Netherlands and England regarding hospital-at-home for
      COPD exacerbations can be explained in three ways. Hospital-at-home has proved to
      be a safe alternative for hospital care for selected patients, and should be
      considered as a treatment option for COPD exacerbations in the Netherlands.

PMID- 22977432
TI  - Collaboration process for integrated social and health care strategy
      implementation.
AB  - OBJECTIVE: To present a collaboration process for creating a roadmap for the
      implementation of a strategy for integrated health and social care. The developed
      collaboration process includes multiple phases and uses electronic group decision
      support system technology (GDSS). METHOD: A case study done in the South Karelia
      District of Social and Health Services in Finland during 2010-2011. An expert
      panel of 13 participants was used in the planning process of the strategy
      implementation. The participants were interviewed and observed during the case
      study. RESULTS: As a practical result, a roadmap for integrated health and social
      care strategy implementation has been developed. The strategic roadmap includes
      detailed plans of several projects which are needed for successful integration
      strategy implementation. As an academic result, a collaboration process to create
      such a roadmap has been developed. CONCLUSIONS: The collaboration process and
      technology seem to suit the planning process well. The participants of the
      meetings were satisfied with the collaboration process and the GDSS technology.
      The strategic roadmap was accepted by the participants, which indicates
      satisfaction with the developed process.

PMID- 22977433
TI  - Integrated care cannot be designed in Whitehall.
AB  - In recent years England has introduced a number of initiatives to promote more
      integrated care. Two contrasting examples are the GP-led health centres and the
      Integrated Care Pilots announced in the interim and final reports, respectively,
      of the NHS Next Stage Review in 2007-2008. The GP-led health centres were
      proposed as a very centralised, prescriptive approach where the aim was that all
      the NHS should adopt the same model of facilitating integration through co
      location. Integrated Care Pilots, on the other hand, looked to the NHS to suggest
      their own solutions to improve integration, resulting in a variety of solutions
      tailored to the needs of localities. Although the results of the evaluation of
      the Integrated Care Pilots have been equivocal, this bottom-up approach must be
      the right way to foster integrated care. Long-term commitment to integrate care
      is needed, as well as more exploration of integration between primary care and
      hospitals.

PMID- 22977434
TI  - Integrated care for diabetes-a Singapore approach.
AB  - BACKGROUND: The prevalence of diabetes mellitus is 12.7% in Singapore. Managing
      people with diabetes in the community may be needed to reduce unnecessary
      utilisation of expensive specialist resources and to reduce hospital waiting
      times for patients with complications.  CARE PRACTICE: The Singapore General
      Hospital (SGH) Delivering on Target (DOT) Programme was launched in 2005 to right
      site clinically stable diabetic patients from the hospital to private DOT GPs.
      The Chronic Disease Management Office (CDMO) was established and a fully
      customised DOT information technology (IT) system was developed. Three
      initiatives were implemented: (i) Subsidised drug delivery programme, (ii)
      Diagnostic tests incentive programme, and (iii) Allied healthcare incentive
      programme. DISCUSSION: Right-siting was enabled through patient incentives that
      eased the burden of out-of-pocket expenditure. Right Siting Officers (RSOs)
      maintained a general oversight of the patient pathway. The integrated system
      supported shared care follow-up by enabling DOT GPs to share updates on the
      patients' health status with the referring specialists. CONCLUSION: A coherent
      process across all healthcare providers similar to the SGH DOT Programme may
      facilitate efforts to shift the care for people with diabetes to the community
      and to provide integrated care. Successful integration may require incentives for
      institutional partners and patients.

PMID- 22977435
TI  - A web-based communication system for integrated care in cerebral palsy:
      experienced contribution to parent-professional communication.
AB  - INTRODUCTION: To improve communication in the integrated care setting of children
      with cerebral palsy, we developed a web-based system for parent-professional and
      inter-professional communication. The present study aimed to evaluate parents'
      experiences regarding the system's contribution to their communication with
      professionals during a six-months pilot in three Dutch care regions. In addition,
      factors associated with parents' system use and non-use were analyzed. THEORY AND
      METHODS: The system's functional specifications were based on key elements of the
      Chronic Care Model and quality dimensions formulated by the Institute of
      Medicine. At baseline, parents completed a T0-questionnaire on their experiences
      regarding sufficiency of contact, accessibility of professionals, timeliness of
      information exchange, consistency of information and parents' role as messenger
      of information and/or care coordinator. After the pilot, parents completed a T1
      questionnaire on their experiences regarding the system's contribution to each of
      these aspects. RESULTS: Of the 30 participating parents 21 had used the system,
      of which 20 completed the T1-questionnaire. All these parents indicated that they
      had experienced a contribution of the system to parent-professional
      communication, especially with respect to accessibility of professionals,
      sufficiency of contact and timeliness of information exchange, and to a lesser
      extent consistency of information and parents' messenger/coordinator role. In
      comparison with non-users, users had less positive baseline experiences with
      accessibility and a higher number of professionals in the child's care network.
      CONCLUSIONS: All users indicated a contribution of the system to parent
      professional communication, although the extent of the experienced contribution
      varied considerably. Based on the differences found between users and non-users,
      further research might focus on the system's value for complex care networks and
      problematic access to professionals.

PMID- 22977437
TI  - Early childhood wheezing: various natural courses and their relationship to later
      asthma.
AB  - Wheezing is one of the most frequent complaints that lead to the use of medical
      resources in younger children. Generally, wheezing is caused by bronchiolitis and
      resolves spontaneously without recurrence, but sometimes, wheezing can progress
      into asthma. Early data on the natural history of childhood wheezing was mostly
      obtained from retrospective reviews of medical records or from questionnaires,
      which made it difficult to exclude biases. Now that many cohort studies are
      available, reviewing the results of birth cohort studies makes it possible to
      understand the natural course of early childhood wheezing and the risk factors
      for asthma. In this study, we have reviewed the various phenotypes of early
      childhood wheezing and their natural courses to help select the most appropriate
      management modalities for the different types of early childhood wheezing.

PMID- 22977436
TI  - Molecular Imaging Probe Development using Microfluidics.
AB  - In this manuscript, we review the latest advancement of microfluidics in
      molecular imaging probe development. Due to increasing needs for medical imaging,
      high demand for many types of molecular imaging probes will have to be met by
      exploiting novel chemistry/radiochemistry and engineering technologies to improve
      the production and development of suitable probes. The microfluidic-based probe
      synthesis is currently attracting a great deal of interest because of their
      potential to deliver many advantages over conventional systems. Numerous chemical
      reactions have been successfully performed in micro-reactors and the results
      convincingly demonstrate with great benefits to aid synthetic procedures, such as
      purer products, higher yields, shorter reaction times compared to the
      corresponding batch/macroscale reactions, and more benign reaction conditions.
      Several 'proof-of-principle' examples of molecular imaging probe syntheses using
      microfluidics, along with basics of device architecture and operation, and their
      potential limitations are discussed here.

PMID- 22977438
TI  - Effects of phytoestrogen on sexual development.
AB  - Phytoestrogen is an estrogenic compound that occurs naturally in plants. The most
      common sources of phytoestrogen are soybean products, which contain high levels
      of isoflavones. This compound, which has structural similarity with estrogen, can
      act as an estrogen receptor agonist or antagonist. Animal studies provide
      evidence of the significant effects of phytoestrogen on sexual development,
      including altered pubertal timing, impaired estrous cycling and ovarian function,
      and altered hypothalamus and pituitary functions. Although human studies
      examining the effects of phytoestrogen on sexual development are extremely
      limited, the results of some studies agree with those of the animal studies. In
      this paper, we review the possible mechanism of phytoestrogen action and the
      evidence showing the effects of phytoestrogen on sexual development in animal and
      human studies.

PMID- 22977439
TI  - Parental concerns about their premature infants' health after discharge from the
      neonatal intensive care unit: a questionnaire survey for anticipated guidance in
      a neonatal follow-up clinic.
AB  - PURPOSE: The aim of this study was to develop an appropriate nursing information
      guideline according to corrected age, after investigating parents' concerns about
      the growth, development, and diseases of their premature infants after discharge
      from the neonatal intensive care unit (NICU). METHODS: The parents of premature
      infants (birth weight, <2,500 g; gestational age, <37 weeks) who went to a
      neonatal follow-up clinic after NICU discharge at Seoul St. Mary's Hospital from
      January 2005 to December 2009, were asked with regard to their concerns about
      their infants through a questionnaire survey. The results of physical
      examinations, including body measurements and neurodevelopmental status at 4, 8,
      12, and 18 months of corrected age, were retrospectively reviewed in 390 infants.
      RESULTS: The most common parental concerns were developmental delay, poor growth,
      and feeding and nutritional problems. Parental concerns about developmental
      delay, growth failure in improvement in body weight and length, and
      overweightness were high in specificity but very low in sensitivity. After NICU
      discharge, 30% of premature infants experienced infectious diseases before 18
      months of corrected age, the most common of which was respiratory tract
      infection. CONCLUSION: For guiding of premature infants in outpatient day clinics
      after NICU discharge, it is necessary to identify the parents' highest concerns,
      to educate them about the possibilities of growth and neurodevelopmental
      disabilities in their infants and to provide them with handouts containing
      guidelines on the management of infectious diseases, especially respiratory
      infections.

PMID- 22977440
TI  - Birth statistics of high birth weight infants (macrosomia) in Korea.
AB  - PURPOSE: The authors analyzed the trend from the birth-related statistics of high
      birth weight infants (HBWIs) over 50 years in Korea from 1960 to 2010. METHODS:
      We used 2 data sources, namely, the hospital units (1960's to 1990's) and
      Statistics Korea (1993 to 2010). The analyses include the incidence of HBWIs,
      birth weight distribution, sex ratio, and the relationship of HBWI to maternal
      age. RESULTS: The hospital unit data indicated the incidence of HBWI as 3 to 7%
      in the 1960's and 1970's and 4 to 7% in the 1980's and 1990's. Data from
      Statistics Korea indicated the percentages of HBWIs among total live births
      decreased over the years: 6.7% (1993), 6.3% (1995), 5.1% (2000), 4.5% (2000), and
      3.5% (2010). In HBWIs, the birth weight rages and percentage of incidence in
      infants' were 4.0 to 4.4 kg (90.3%), 4.5 to 4.9 kg (8.8%), 5.0 to 5.4 kg (0.8%),
      5.5 to 5.9 kg (0.1%), and >6.0 kg (0.0%) in 2000 but were 92.2%, 7.2%, 0.6%,
      0.0%, and 0.0% in 2009. The male to female ratio of HBWIs was 1.89 in 1993 and
      1.84 in 2010. In 2010, the mother's age distribution correlated with low (4.9%),
      normal (91.0%), and high birth weights (3.6%): an increase in mother's age
      resulted in an increase in the frequency of low birth weight infants (LBWIs) and
      HBWIs. CONCLUSION: The incidence of HBWIs for the past 50 years has been dropping
      in Korea. The older the mother, the higher was the risk of a HBWI and LBWI. We
      hope that these findings would be utilized as basic data that will aid those
      managing HBWIs.

PMID- 22977441
TI  - Continuous renal replacement therapy in neonates weighing less than 3 kg.
AB  - PURPOSE: Continuous renal replacement therapy (CRRT) is becoming the treatment of
      choice for supporting critically ill pediatric patients. However, a few studies
      present have reported CRRT use and outcome in neonates weighing less than 3 kg.
      The aim of this study is to describe the clinical application, outcome, and
      complications of CRRT in small neonates. METHODS: A retrospective review was
      performed in 8 neonatal patients who underwent at least 24 hours of pumped
      venovenous CRRT at the Samsung Medical Center in Seoul, Korea, between March 2007
      and July 2010. Data, including demographic characteristics, diagnosis, vital
      signs, medications, laboratory, and CRRT parameters were recorded. RESULTS: The
      data of 8 patients were analyzed. At the initiation of CRRT, the median age was 5
      days (corrected age, 38(+2) weeks to 23 days), and the median body weight was
      2.73 kg (range, 2.60 to 2.98 kg). Sixty-two patient-days of therapy were
      reviewed; the median time for CRRT in each patient was 7.8 days (range, 1 to 37
      days). Adverse events included electrolyte disturbances, catheter-related
      complications, and CRRT-related hypotension. The mean circuit functional survival
      was 13.9+/-8.6 hours. Overall, 4 patients (50%) survived; the other 4 patients,
      who developed multiorgan dysfunction syndrome, died. CONCLUSION: The
      complications of CRRT in newborns are relatively high. However, the results of
      this study suggest that venovenous CRRT is feasible and effective in neonates
      weighing less than 3 kg under elaborate supportive care. Furthermore, for using
      potential benefit of CRRT in neonates, efforts are required for prolonging filter
      survival.

PMID- 22977442
TI  - A case of cytomegalovirus-negative Menetrier's disease with eosinophilia in a
      child.
AB  - Menetrier's disease is a rare form of acquired gastropathy characterized by giant
      rugal folds in the stomach and protein-losing gastropathy. Children with
      Menetrier's disease tend to follow a benign self-limited course with symptoms
      typically completely resolving within 2 to 10 weeks in contrast to the chronic
      course in adults. A 9-year-old girl presented with a history of gradually
      worsening abdominal distension, increasing body weight, and abdominal pain for 2
      weeks. Physical examination on admission indicated periorbital swelling, pitting
      edema in both the legs, and abdominal distension with mild diffuse tenderness and
      shifting dullness. Laboratory tests on admission showed hypoalbuminemia,
      hypoproteinemia, and peripheral eosinophilia. The test result for
      anticytomegalovirus immunoglobulin M was negative. Increased fecal alpha 1 anti
      trypsin excretion was observed. Radiological findings showed massive ascites and
      pleural effusion in both the lungs. On gastroscopy, large gastric folds,
      erythema, erosion, and exudation were noted in the body and fundus of the
      stomach. Microscopic findings showed infiltration of eosinophils and neutrophils
      in the gastric mucosa. Her symptoms improved with conservative treatment from day
      7 of hospitalization and resolved completely.

PMID- 22977443
TI  - Bronchial compression in an infant with isolated secundum atrial septal defect
      associated with severe pulmonary arterial hypertension.
AB  - Symptomatic pulmonary arterial hypertension (PAH) in patients with isolated
      atrial septal defect (ASD) is rare during infancy. We report a case of isolated
      ASD with severe PAH in an infant who developed airway obstruction as cardiomegaly
      progressed. The patient presented with recurrent severe respiratory insufficiency
      and failure to thrive before the repair of the ASD. Echocardiography confirmed
      volume overload on the right side of heart and severe PAH (tricuspid
      regurgitation [TR] with a peak pressure gradient of 55 to 60 mmHg). The chest
      radiographs demonstrated severe collapse of both lung fields, and a computed
      tomography scan showed narrowing of the main bronchus because of an intrinsic
      cause, as well as a dilated pulmonary artery compressing the main bronchus on the
      left and the intermediate bronchus on the right. ASD patch closure was performed
      when the infant was 8 months old. After the repair of the ASD, echocardiography
      showed improvement of PAH (TR with a peak pressure gradient of 22 to 26 mmHg),
      and the patient has not developed recurrent respiratory infections while showing
      successful catch-up growth. In infants with symptomatic isolated ASD, especially
      in those with respiratory insufficiency associated with severe PAH, extrinsic
      airway compression should be considered. Correcting any congenital heart diseases
      in these patients may improve their symptoms.

PMID- 22977444
TI  - Sequential magnetic resonance spectroscopic changes in a patient with nonketotic
      hyperglycinemia.
AB  - Nonketotic hyperglycinemia (NKH) is a rare inborn error of amino acid metabolism.
      A defect in the glycine cleavage enzyme system results in highly elevated
      concentrations of glycine in the plasma, urine, cerebrospinal fluid, and brain,
      resulting in glycine-induced encephalopathy and neuropathy. The prevalence of NKH
      in Korea is very low, and no reports of surviving patients are available, given
      the scarcity and poor prognosis of this disease. In the current study, we present
      a patient with NKH diagnosed on the basis of clinical features, biochemical
      profiles, and genetic analysis. Magnetic resonance spectroscopy (MRS) allowed the
      measurement of absolute glycine concentrations in different parts of the brain
      that showed a significantly increased glycine peak, consolidating the diagnosis
      of NKH. In additional, serial MRS follow-up showed changes in the
      glycine/creatinine ratios in different parts of the brain. In conclusion, MRS is
      an effective, noninvasive diagnostic tool for NKH that can be used to distinguish
      this disease from other glycine metabolism disorders. It may also be useful for
      monitoring NKH treatment.

PMID- 22977445
TI  - Epidemiology and clinical management of pulmonary hypertension in children.
AB  - Pulmonary hypertension (PH) is a clinical hemodynamic syndrome characterized by
      increased pulmonary artery pressure and pulmonary vascular resistance. It can
      cause right ventricular failure, and even death. Pediatric PH is not very common,
      but is a greatly hazardous disease that leads to a high mortality rate.
      Therefore, many registry organizations have been established in the world to
      strengthen the study of diagnosis and treatment of the disease, and improve the
      understanding of pediatric PH. This article reviewed recently published
      researches, as well as presented a comprehensive understanding of PH, including
      definition, classification, epidemiology, prognosis and treatment.

PMID- 22977446
TI  - Possible regulation of platelets by native and modified low density lipoprotein
      cholesterol particles.

PMID- 22977447
TI  - Postoperative B-type natriuretic Peptide levels associated with prolonged
      hospitalization in hypertensive patients after non-cardiac surgery.
AB  - BACKGROUND AND OBJECTIVES: B-type natriuretic peptide (BNP) is an important
      marker for the diagnosis of heart failure and is useful towards predicting
      morbidity and mortality after non-cardiac surgery. Nevertheless, information on
      the relationship between postoperative BNP levels and perioperative prognosis
      after non-cardiac surgery is scarce. The purpose of the study was to assess
      whether postoperative BNP levels could be used as a predictor of prolonged
      hospitalization in elderly hypertensive patients after non-cardiac surgery.
      SUBJECTS AND METHODS: Ninety-seven (97) patients, aged 55 years or older (mean
      age: 73.12+/-10.05 years, M : F=24 : 73) were enrolled in a prospective study
      from May 2005 through August 2010. All patients underwent total knee or hip
      replacement. Postoperative BNP and other diagnostic data were recorded within 24
      hours of surgery. Patients that required a prolonged hospital stay due to
      operative causes, such as wound infection and re-operation, were excluded.
      RESULTS: The length of hospital stay was significantly correlated with
      postoperative BNP levels (p=0.031). Receiver operating characteristic curves
      demonstrated postoperative BNP levels as predictors of hospital stay >=30 days
      with areas under the curve of 0.774 (95% confidence interval: 0.679-0.87,
      p<0.0001). A BNP cut-off value above 217.5 pg/mL had a sensitivity of 80.6% and a
      specificity of 66.7% for predicting postoperative hospital stays of 30 days or
      more. CONCLUSION: Postoperative BNP levels may predict the length of hospital
      stays after non-cardiac surgery in hypertensive patients. Elevated BNP levels
      were associated with prolonged hospitalization after elective orthopedic surgery.

PMID- 22977448
TI  - Clinical characteristics of acute aortic syndrome in korean patients: from the
      korean multi-center registry of acute aortic syndrome.
AB  - BACKGROUND AND OBJECTIVES: Acute aortic syndrome (AAS) is a heterogeneous group
      of disorders that often present with severe chest or back pain. It includes acute
      aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and
      penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis
      have not been studied in a large number of Korean patients. Therefore, we
      organized a multi-center registry to identify the clinical characteristics and
      treatment patterns, as well as long-term outcomes in Korean patients with AAS.
      SUBJECTS AND METHODS: Five-hundred twenty-eight patients, who had been diagnosed
      with AAS, were enrolled into this registry from 10 centers. On a retrospective
      basis, we collected demographic, laboratory, imaging data, as well as follow-up
      clinical outcomes by reviewing medical records from individual centers. All the
      data were collected in core lab and analyzed in detail. RESULTS: The mean patient
      age was 60.1+/-14.5 years; the male-to-female ratio was M : F=297 : 231. The
      prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes
      (52, 11.1%). The components of AAS that are included in this study are acute AD
      (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients
      diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with
      Stanford B were 54.4% of enrolled patients. Among nearly half of the patients
      were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and
      4.3% underwent endovascular treatment. Overall, the in-hospital event rate was
      21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was
      42.8 months and there showed 22.9% of total event and 10.1% of death during this
      period. CONCLUSION: By organizing a multi-center registry of AAS, we could
      identify the characteristics of AAS in real-world Korean patients. Further,
      prospective study is warranted with a larger number of patients.

PMID- 22977449
TI  - Antithrombotic or anti-platelet agents in patients undergoing permanent pacemaker
      implantation.
AB  - BACKGROUND AND OBJECTIVES: The growing implantations of electrophysiological
      devices in the context of increasing rates of chronic antithrombotic therapy in
      cardiovascular disease patients underscore the importance of an effective
      periprocedural prophylactic strategy for prevention of bleeding complications. We
      assessed the risk of significant bleeding complications in patients receiving
      anti-platelet agents or anticoagulants at the time of permanent pacemaker (PPM)
      implantation. SUBJECTS AND METHODS: We reviewed bleeding complications in
      patients undergoing PPM implantation. The use of aspirin or clopidogrel was
      defined as having taking drugs within 5 days of the procedure and warfarin was
      changed to heparin before the procedure. A significant bleeding complication was
      defined as a bleeding incident requiring pocket exploration or blood transfusion.
      RESULTS: Permanent pacemaker implantations were performed in 164 men and 96
      women. The mean patient age was 73+/-11 years old. Among the 260 patients, 14
      patients took warfarin (in all of them, warfarin was changed to heparin at least
      3 days before procedure), 54 patients took aspirin, 4 patients took clopidogrel,
      and 25 patients took both. Significant bleeding complications occurred in 8
      patients (3.1%), all of them were patients with heparin bridging (p<0.0001).
      Heparin bridging markedly increased the length of required hospital stay when
      compare with other groups and the 4 patients (1.5%) that underwent the pocket
      revision for treatment of hematoma. CONCLUSION: This study suggests that hematoma
      formation after PPM implantation was rare, even among those who had taken the
      anti-platelet agents. The significant bleeding complications frequently occurred
      in patients with heparin bridging therapy. Therefore, heparin bridging therapy
      was deemed as high risk for significant bleeding complication in PPM
      implantation.

PMID- 22977450
TI  - Simvastatin and losartan differentially and synergistically inhibit
      atherosclerosis in apolipoprotein e(-/-) mice.
AB  - BACKGROUND AND OBJECTIVES: Since statins and angiotensin receptor blockers are a
      frequently prescribed combination in patients with atherosclerotic cardiovascular
      diseases, we tested the interactive effects of simvastatin and losartan on
      atherosclerosis in apolipoprotein E (apoE)(-/-) mice. MATERIALS AND METHODS:
      Apolipoprotein E(-/-) mice were fed a high-fat, high-cholesterol (HFHC) diet for
      12 weeks, with and without simvastatin (40 mg/kg) and/or losartan (20 mg/kg). The
      mice were divided into 5 groups and were fed as follows: regular chow (control
      diet, n=5), HFHC diet (n=6), HFHC diet with losartan (n=6), HFHC diet with
      simvastatin (n=6), and HFHC diet with both losartan and simvastatin (n=6).
      RESULTS: Losartan treatment in apoE(-/-) mice significantly decreased
      atherosclerotic lesion areas in whole aortic strips stained with Oil Red O. The
      plaque area measured at the aortic sinus level was reduced significantly by 17%
      (HFHC; 346830.9+/-52915.8 um(2) vs. HFHC plus losartan; 255965.3+/-74057.7 um(2),
      p<0.05) in the losartan-treated group. Simvastatin and simvastatin plus losartan
      treatments reduced macrophage infiltration into lesions by 33% (HFHC; 183575.6+/
      43211.2 um(2) vs. HFHC plus simvastatin; 120556.0+/-39282.8 um(2), p<0.05) and
      44% (HFHC; 183575.6+/-43211.2 um(2) vs. HFHC plus simvastatin and losartan;
      103229.0+/-8473.3 um(2), p<0.001, respectively). In mice fed the HFHC diet alone,
      the smooth muscle cell layer in the aortic media was almost undetectable. In mice
      co-treated with losartan and simvastatin, the smooth muscle layer was more than
      60% preserved (p<0.05). Given alone, losartan showed a slightly stronger effect
      than simvastatin; however, treatment with losartan plus simvastatin induced a
      greater inhibitory effect on atherosclerosis than either drug given alone. Serum
      lipid profiles did not differ significantly among the groups. CONCLUSION:
      Losartan displayed anti-atherosclerotic effects in apoE(-/-) mice that were
      equivalent to or greater than the effects of simvastatin. Combined treatment with
      these drugs had greater effect than either drug alone.

PMID- 22977451
TI  - Lack of association between low density lipoprotein particle size and on
      treatment platelet reactivity in patients with coronary artery disease.
AB  - BACKGROUND AND OBJECTIVES: Small dense low density lipoproteins (sd-LDL) are a
      risk factor for coronary artery disease and are known to stimulate platelet
      function in vitro. This study aimed to evaluate whether high proportion of sd-LDL
      is associated with high on-treatment platelet reactivity (HOPR). SUBJECTS AND
      METHODS: From January 2009 to March 2010, 439 subjects (mean age: 64.3+/-9.7,
      Male : Female=306 : 133) were enrolled from the low density LIPOProtein
      cholesterol Size measurement Registry with coronary artery disease, who had
      undergone elective percutaneous coronary intervention and measured both LDL
      particle size and on-treatment platelet reactivity (OPR). Mean LDL particle size
      was measured by gradient gel electrophoresis (Quantimetrix, LipoprintTM) and OPR
      by the VerifyNowTM system (aspirin and P2Y12). RESULTS: Between pattern A (large,
      buoyant LDL dominant) and B (sd-LDL dominant) population, there were no
      significant difference in OPR to aspirin (441.3+/-71.9 vs. 434.07+/-63.45 aspirin
      reaction units, p=0.351) or clopidogrel (237.9+/-87.3 vs. 244.9+/-80.7 P2Y12
      reaction units, p=0.465). There was no difference in LDL particle size between
      patients with HOPR compared with non-HOPR patients (aspirin: 26.8+/-0.5 vs.
      26.7+/-0.6 nm, p=0.078, clopidogrel: 26.7+/-0.6 vs. 26.8+/-0.5 nm, p=0.857).
      Pearson's correlation coefficients between LDL particle size and platelet
      reactivity were not statistically significant (aspirin assay: r=0.080, p=0.098,
      P2Y12 assay: r=-0.027, p=0.568). CONCLUSION: There was no significant association
      between LDL particle size and OPR in patients with coronary artery disease.

PMID- 22977452
TI  - Rupture and spontaneous sealing of a coronary aneurysm after deployment of drug
      eluting stent.
AB  - Lesions with coronary artery aneurysm (CAA) can become complicated during
      percutaneous coronary intervention. Here, we report a case of a 78-year-old man
      who developed a rupture, and spontaneous sealing of the CAA occurred after stent
      implantation, as shown by computed tomography coronary angiography.

PMID- 22977453
TI  - A case of severe pulmonary thromboembolism in a young male with klinefelter
      syndrome.
AB  - A young male patient diagnosed with Klinefelter syndrome was admitted to our
      hospital via the emergency room with chief complaints of acute chest pain and
      dyspnea. Pulmonary thromboembolism was diagnosed from his chest CT images. His
      symptoms improved after he underwent thrombolysis and anticoagulation treatment.
      Klinefelter syndrome has a tendency towards hypercoagulability due to hormonal
      imbalance and one or more inherited thromophilic factors. Thus, Klinefelter
      syndrome patients with a past medical history of venous thromboembolism require
      continuous oral anticoagulation therapy for a period of at least six months.

PMID- 22977454
TI  - Right Ventricular Myocardial Infarction due to Right Coronary Artery Total
      Occlusion Originating From the Distal Left Circumflex Artery.
AB  - An isolated single coronary artery is rare but often associated with other
      congenital cardiac malformations and myocardial ischemia. We report a rare case
      of right ventricular myocardial infarction due to total occlusion of the right
      coronary artery originating from the distal left circumflex artery.

PMID- 22977455
TI  - Polyarteritis nodosa complicated by chronic total occlusion accompanying
      aneurysms on all coronary arteries.
AB  - Polyarteritis nodosa (PAN) is characterized by inflammatory necrosis of medium
      sized arteries. PAN can also be associated with stenosis or aneurysm of the
      coronary artery. However, the involvement of PAN at a coronary artery is usually
      asymptomatic, which makes it difficult to diagnose. In addition, all of the three
      main coronary arteries involved with chronic total occlusion (CTO) is a rare
      finding in patients with PAN. We report a patient that presented with PAN
      complicated by CTO and aneurysms of three main coronary arteries, without typical
      symptoms of angina.

PMID- 22977456
TI  - Cardiac sarcoidosis presenting with complete atrioventricular block and sustained
      monomorphic ventricular tachycardia.
AB  - Sarcoidosis is a rare but potentially fatal multisystem granulomatous disease of
      unknown etiology. While a number of clinical manifestations may develop, cardiac
      involvement (prior to or coincident with sarcoidosis of other organs) is an
      important prognostic factor. Recently, we encountered a patient with cardiac
      sarcoidosis who presented with complete atrioventricular (AV) block and sustained
      ventricular tachycardia. An implantable cardioverter-defibrillator was inserted
      as a precautionary measure for ventricular tachycardia and symptomatic complete
      AV block. (18)F-fluoro-2-deoxyglucose positron emission tomography confirmed a
      dramatic response to high-dose steroid at four weeks, as demonstrated by a marked
      decrease in cardiac sarcoid activity from baseline status.

PMID- 22977457
TI  - Radiofrequency catheter ablation for unifocal premature ventricular complexes
      triggering recurrent ventricular fibrillations in a young man without structural
      heart disease.
AB  - A 17-year-old man was referred for aborted sudden cardiac death. Ventricular
      fibrillation (VF) was recorded by automated external defibrillator. Post
      resuscitation electrocardiograms showed frequent monomorphic premature
      ventricular complexes (PVCs), with left bundle branch block configuration and
      inferior axis. Cardiac arrest due to VF recurred twice within the initial 42
      hours. Rhythm monitoring revealed multiple episodes of sustained VF triggered by
      a triplet of monomorphic PVCs having similar morphology with isolated PVCs.
      Comprehensive cardiologic workup revealed no structural heart disease and ion
      channelopathies. With the impression of idiopathic VF triggered by unifocal PVCs
      of right ventricular outflow tract (RVOT) origin, radiofrequency catheter
      ablation was performed to prevent frequent VF recurrence before implantable
      cardioverter-defibrillator (ICD) implantation. After successful ablation of the
      origin of unifocal PVCs at anterolateral wall of RVOT, the burden of PVCs
      decreased remarkably and VF did not recur. The patient was discharged after ICD
      implantation.

PMID- 22977458
TI  - Ostial coronary stenosis and severe aortic stenosis in a patient with familial
      hypercholesterolemia.

PMID- 22977459
TI  - Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia.
AB  - Pneumonia is a common cause of morbidity and mortality worldwide. While
      antibiotics are generally effective for the treatment of infection, the emergence
      of resistant strains of bacteria threatens their success. The osteopathic medical
      profession has designed a set of manipulative techniques called lymphatic pump
      techniques (LPT), to enhance the flow of lymph through the lymphatic system.
      Clinically, LPT is used to treat infection and oedemaand might be an effective
      adjuvant therapy in patients with pneumonia.The immune system uses the lymphatic
      and blood systems to survey to rid the body of pathogens; however, only recently
      have the effects of LPT on the lymphatic and immune systems been investigated.
      This short review highlightsclinical and basic science research studies that
      support the use of LPT to enhance the lymphatic and immune systems and treat
      pneumonia, and discusses the potential mechanisms by which LPT benefits patients
      with pneumonia.

PMID- 22977460
TI  - WATER, ENERGY AND LIFE: FRESH VIEWS FROM THE WATER'S EDGE.
AB  - Recent observations have shown an unexpected feature of water adjacent to
      hydrophilic surfaces: the presence of wide interfacial zone that excludes
      solutes. The exclusion zone is charged, while the water beyond is oppositely
      charged, yielding a battery-like feature. The battery is powered by absorbed
      radiant energy. Implications of this energetic feature are discussed. It appears
      that the presence of this 'exclusion zone' may play an important role in the
      behavior of aqueous systems.

PMID- 22977461
TI  - Impact strength of denture base and reline acrylic resins: An in vitro study.
AB  - This study evaluated the impact strength of a denture base resin (Lucitone 550-L)
      and four reline resins (Tokuyama Rebase II-T; Ufi Gel Hard-U; New Truliner-NT,
      and Kooliner-K), both intact and in a reline combination (L/L, L/T, L/U, L/NT,
      and L/K). For each group (n = 20), half of the specimens were thermocycled before
      testing. Charpy tests were performed, and the impact strengths were calculated.
      Data were analyzed by two-way analyses of variance and Tukey's test (p = 0.05).
      For the intact groups, mean impact strength values for L (1.65 and 1.50) were
      significantly higher than those of the reline resins (0.38-1.17). For the relined
      groups, the highest mean impact strength values were produced by L/T (5.76 and
      5.12), L/NT (6.20 and 6.03), and L/K (5.60 and 5.31) and the lowest by L/U (0.76
      and 0.78). There were no significant differences between L and L/L. Thermocycling
      reduced the impact strength of T (from 0.73 to 0.38) and L/L (from 1.82 to 1.56).

PMID- 22977462
TI  - NMT1 (N-myristoyltransferase 1).

PMID- 22977463
TI  - Induced pluripotent stem cell technology and stem cell therapy for diabetes.
AB  - Although diabetes can be managed clinically with the use of insulin injections,
      it remains an incurable and inconvenient disorder. In the long-term, it is
      associated with a number of clinical complications, such as cardiovascular
      disease, resulting in a desire for the development of new methodologies to
      replace defective cells and provide a lasting normality without the need for drug
      treatment. Stem cells, including induced pluripotent stem cells, offer the
      possibility of generating cells suitable for transplantation due to their
      capacity to differentiate into all tissue lineages. However, many issues must be
      addressed before this type of treatment becomes a reality, including the need for
      a greater understanding of the underlying biology involved in the onset of
      diabetes.

PMID- 22977464
TI  - Immunohistochemical analysis of integrins alphavbeta3, alphavbeta5 and
      alpha5beta1, and their ligands, fibrinogen, fibronectin, osteopontin and
      vitronectin, in frozen sections of human oral head and neck squamous cell
      carcinomas.
AB  - Integrins mediate the interaction of cells with the extracellular matrix and are
      believed to be involved in tumor cell survival and metastasis, and in tumor
      angiogenesis. We used immunohistochemistry of fresh-frozen human tumor tissues to
      analyze the presence of integrins alphavbeta3, alphavbeta5 and alpha5beta1, which
      are believed to be involved in tumor growth and migration, together with integrin
      ligands, vitronectin, osteopontin, fibronectin and fibrinogen, in human oral
      squamous cell carcinomas. Samples of squamous cell carcinomas and control tissues
      from patients without cancer undergoing oral or maxillofacial surgery were frozen
      in liquid nitrogen within 30 min of removal. Frozen sections were prepared, and
      the presence of integrins or ligands was visualized using standard
      immunohistochemistry (APAAP) with a blinded evaluation. Comparison of samples
      from the 40 oral cancer patients and the 20 controls revealed increased staining
      in tumors compared with the controls, and staining was demonstrated for
      alphavbeta3 in endothelia. alphavbeta5 staining was increased in the tumor
      samples, but this was associated with increased expression in stroma rather than
      in endothelia. Modestly increased expression of alpha5beta1 was observed in the
      tumor samples, and this was associated with tumor cells, endothelia and stroma.
      Expression of ligands for the integrins varied between tissue types, with
      increased fibrinogen and fibronectin expression in tumor endothelia. Confirmation
      of the presence of these integrins and their association with tumor cells,
      endothelia or stroma suggests their potential for these integrins in human oral
      tumors. Overall, the increased expression of integrins within tumors,
      particularly expression associated with endothelial cells, supports the principle
      of selective integrin blockade as a novel anticancer strategy.

PMID- 22977465
TI  - Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated
      with Coptidis rhizoma aqueous extract.
AB  - Coptidis rhizoma (CR; Huanglian in Chinese) has been used for the treatment of
      cancer in Chinese medicine, and recent studies have supported its use in cancer
      therapy. MicroRNAs (miRNAs) play an important role in the pathophysiology of
      human cancers. We examined alterations in the miRNA profile of hepatocellular
      carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract
      (CRAE). An on-chip microarray method was used to detect alterations in the
      expression profile of miRNAs in human HCC MHCC97-L cells after exposure to 175
      MUg/ml CRAE. Altered expression of several miRNAs was detected in the MHCC97-L
      cells after treatment with 175 MUg/ml CRAE. The microarray results were validated
      by quantitative real-time PCR (qRT-PCR). Consistent results were obtained; qRT
      PCR confirmed that both miR-21 and miR-23a were significantly up-regulated.
      TargetScan and PicTar microRNA databases were used to predict the possible target
      genes of the altered miRNAs. The results showed that the altered miRNAs after
      CRAE treatment may serve as markers for the therapy of liver cancer. To the best
      of our knowledge, this is the first report on the up-regulation of miRNAs, miR21
      and miR23a in human liver cancer cells treated with CRAE. Our results suggest
      that CRAE targets miR-21 and miR-23a in liver cancer cells supporting the
      potential application of CRAE in the treatment of HCC.

PMID- 22977466
TI  - Antioxidant and antitumor activities of water extracts from the root of Actinidia
      kolomikta.
AB  - The genus of Actinidia is widely distributed throughout the Asian continent.
      Specific Actinidia species have been used as health foods and medical products
      for cancer treatment. Actinidia kolomikta is a species of wild plant that grows
      in the northern part of Indochina. However, few studies on its bioactivity have
      been reported. In this study, the polysaccharide and polyphenol contents, the SOD
      like activity and the DPPH radical-scavenging activity of water extracts from the
      root of Actinidia kolomikta produced under different extraction temperatures were
      investigated. Furthermore, the water extraction-ethanol precipitate (WE-EP)
      fraction and the water extraction-ethanol supernatant (WE-ES) fraction were used
      to test the anti-proliferative action on DLD-1 colon cancer cells. Extracts
      produced using the 100 degrees C extraction procedure revealed higher extraction
      yields and antioxidant activities than extracts produced using the 40 degrees C
      extraction procedure. The WE-EP and WE-ES fractions exhibited anti-proliferative
      effects on the DLD-1 cells. Moreover, the WE-ES polyphenol-enriched fraction
      possessed more potent anti-proliferative effects on the DLD-1 cells by inducing
      apoptosis compared to the WE-EP polysaccharide fraction. Medicinal plant extracts
      are generally considered to be relatively non-toxic at low doses and are not
      thought to cause major side effects compared to those observed with drugs. Wild
      A. kolomikta may provide an alternative to currently employed cancer therapies,
      and may be used as a natural health food with antioxidant actions.

PMID- 22977467
TI  - Ostrich produce cross-reactive neutralization antibodies against pandemic
      influenza virus A/H1N1 following immunization with a seasonal influenza vaccine.
AB  - An outbreak of influenza in 2009 was found to be caused by a novel strain of
      influenza virus designated as pandemic influenza A/H1N1 2009. Vaccination with
      recent seasonal influenza vaccines induced little or no cross-reactive antibody
      response to the pandemic influenza virus A/H1N1 2009 in any age group in human
      populations. Accordingly, most people had low immunity against this pathogen,
      thus resulting in the worldwide spread of the infection to produce a so-called
      'pandemic'. This report presents the important finding that ostrich eggs generate
      cross-reactive antibodies to the pandemic influenza virus A/H1N1 following
      immunization of female ostrich with a seasonal influenza vaccine. This simple
      method produced a large amount of antibodies against influenza viruses by one
      female ostrich. An enzyme-linked immunosorbent assay (ELISA) and
      immunocytochemistry indicated that the ostrich antibodies possessed strong cross
      reactivity to the pandemic A/H1N1 as well as to the seasonal A/H1N1, A/H3N2 and B
      viruses. The hemaggregation activities of erythrocytes induced by this pandemic
      strain were also inhibited by the ostrich antibodies. In addition, the
      cytopathological effects of infection with a pandemic virus on MDCK cells were
      clearly inhibited in co-cultures with the ostrich antibodies, thereby indicating
      the neutralization of viral infectivity in the cells. In conclusion, cross
      reactive neutralization antibodies against pandemic influenza virus A/H1N1 2009
      were successfully generated in ostrich eggs produced by females immunized with
      seasonal influenza viral vaccine.

PMID- 22977468
TI  - Predicting response of bladder cancers to gemcitabine and carboplatin neoadjuvant
      chemotherapy through genome-wide gene expression profiling.
AB  - Neoadjuvant chemotherapy with gemcitabine and carboplatin (GC) for invasive
      bladder cancer increases the chance of a radical response for a subset of
      patients, while other patients suffer from severe adverse drug reactions without
      any benefit. To establish a method for predicting the response to chemotherapy
      with GC, the expression profiles of biopsy samples from 37 advanced bladder
      cancers were analyzed using a microarray consisting of 38,500 genes or ESTs. Upon
      analysis of 9 'responder' and 9 'non-responder' tumors, 12 'predictive' genes
      were found to be significantly differentially expressed between the 'responder'
      and 'non-responder' groups, and a numerical prediction scoring system that
      clearly separated the responder group from the non-responder group was
      established. This system accurately predicted the drug responses of 18 of 19
      additional test cases that were reserved from the original 37 cases. Moreover, a
      quantitative PCR-based prediction system was developed that may be feasible for
      routine clinical use, and the sensitivity of invasive bladder cancer to
      neoadjuvant chemotherapy with GC was able to be predicted by the expression
      patterns in this set of genes. Nearly 50% of patients treated with GC or
      methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) therapy have been
      reported to achieve complete or partial response to either of these therapies.
      When we applied this prediction system as well as the system for M-VAC, we
      expected that approximately 80% of the patients would achieve significant tumor
      shrinking (>60%) by selection of either the GC or M-VAC regimens. Our results
      suggest that the two prediction scoring systems lead to achievement of
      'personalized therapy' for the treatment of invasive bladder cancer and should
      improve the quality of life for patients with this disease.

PMID- 22977469
TI  - Suppressive action of resolvin D1 on the production and release of septic
      mediators in D-galactosamine-sensitized endotoxin shock mice.
AB  - Endotoxin/septic shock is a severe condition induced during serious infections
      with Gram-negative bacteria. To evaluate the therapeutic potential of resolvin D1
      (RvD1), a novel pro-resolving molecule, on endotoxin/septic shock, we
      investigated the effect of RvD1 on the extracellular release of high mobility
      group box-1 (HMGB1), the production of inflammatory cytokines, the accumulation
      of peritoneal cells and hepatocyte apoptosis in vivo using a D-galactosamine
      (GalN)-sensitized mouse endotoxin shock model. Serum HMGB1 levels were markedly
      elevated after challenge with lipopolysaccharide (LPS)/D-GalN, and RvD1
      administration significantly reduced HMGB1 levels. Furthermore, the serum levels
      of inflammatory cytokines, such as TNF-alpha, IL-6, IL-10 and macrophage
      chemotactic protein (MCP)-1 were elevated in the endotoxin shock model.
      Importantly, RvD1 administration slightly reduced the TNF-alpha, IL-6 and IL-10
      levels, and further lowered MCP-1 levels. Moreover, RvD1 administration affected
      the peritoneal cell accumulation and decreased the neutrophil population.
      Finally, LPS/D-GalN injection induced apoptosis in the liver (mostly of
      hepatocytes), and RvD1 administration reduced the apoptosis of hepatocytes. These
      observations suggest that RvD1 may be a therapeutic agent for sepsis/endotoxin
      shock by exerting suppressive action on the release and production of septic
      mediators (HMGB1 and inflammatory cytokines), the accumulation of peritoneal
      cells and hepatic apoptosis.

PMID- 22977471
TI  - Establishment of a triple-negative type human breast cancer cell line that
      selectively metastasizes to the lung after orthotropic implantation.
AB  - Triple-negative type breast cancer (TNBC) is a challenge for today's clinical
      practice. To evaluate the efficacy of anticancer drugs and their combination for
      the treatment of patients with metastatic TNBC, an appropriate tumor model of
      metastatic TNBC is required. We developed a breast cancer model in mice that
      highly metastasizes to lung tissue using an established human TNBC cell line, MDA
      MB-231. MDA-MB-231 was implanted intravenously, and lung metastasis nodes were
      collected. The lung metastasis nodes were then implanted into the mammary fat pad
      of female SCID mice, followed by surgical extraction. This procedure was repeated
      an additional two times, and the highly metastatic cell line, MDA-MB-231LLM, was
      established. After orthotropic implantation and surgical extraction, MDA-MB
      231LLM selectively metastasized to the lung, and all of the mice died as a result
      of lung dysfunction. We then evaluated the anti-metastatic effects and survival
      period after treatment with S-1, a fluoropyrimidine derivative using this model.
      Mice were randomized into three groups on day 0. On day 29, lung metastasis was
      observed in all of the control mice, and the mean lung weight was 2.5 times
      greater than that of normal mice (P<0.01). However, after 28 days of consecutive
      treatment with S-1 at a dosage of 10 mg/kg with no apparent toxicity, the lung
      metastasis nodes were apparently fewer, and the lung weight was significantly
      (P<0.01) lower than that of the control. In another experiment, the survival
      period after treatment with S-1 was evaluated. All of the mice in the control
      group died as a result of lung dysfunction, and the median survival period was 35
      days. However, after 28 days of consecutive treatment with S-1 (10 mg/kg), the
      median survival period was prolonged to 55 days (P<0.01). These results suggest
      that this new model will be useful for evaluating the anti-metastatic effects of
      chemotherapeutic agents and the survival period after chemotherapy.

PMID- 22977470
TI  - Reduced expression of TRF1 is associated with tumor progression and poor
      prognosis in oral squamous cell carcinoma.
AB  - The functions of telomeric repeat-binding factor 1 (TRF1) and 2 (TRF2) in oral
      carcinogenesis are largely unexplored. This study examined the relationship
      between the expression of TRF1 and TRF2 and clinicopathological variables and
      survival in oral cavity squamous cell carcinoma (OCSCC). Western blotting and
      immunohistochemistry were used to evaluate the protein expression of TRF1 and
      TRF2 in paired OCSCC patient specimens. Expression of TRF1 and TRF2 was assessed
      by immunohistochemistry in 256 OCSCC patients who underwent tumor resection
      without previous radiotherapy. The results were analyzed using Fisher's exact
      test. Protein expression of TRF1 and TRF2 was significantly lower in the OCSCC
      than in the adjacent non-tumor tissue. Reduced TRF1 and TRF2 levels in 256
      patients, as revealed by immunohistochemistry, were significantly associated with
      aggressive clinicopathological features, such as advanced tumor stage (p<0.001)
      and advanced tumor node metastasis stage (p<0.001). According to Kaplan-Meier
      analysis, reduced TRF1 expression was significantly correlated with an
      unfavorable cumulative 5-year overall survival rate (p<0.001). In conclusion,
      decreased expression of TRF1 was significantly associated with tumor progression
      and poor prognosis in OCSCC patients.

PMID- 22977472
TI  - Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for
      metastatic colorectal cancer.
AB  - To test the safety and immune responses of a novel peptide vaccine derived from
      RNF43 (ring finger protein 43) and TOMM34 (34-kDa translocase of the outer
      mitochondrial membrane) administered in combination with chemotherapy in patients
      with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402
      positive metastatic colorectal cancer patients was conducted. Patients received a
      weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in
      combination with oral UFT (300 mg/m(2)/day) and UZEL (75 mg/day) for 4 weeks,
      followed by 1 week of rest. The protocol consisted of at least two cycles of this
      regimen. After the 2nd cycle, vaccinations were given biweekly or monthly,
      depending on the condition of the patient. Clinical responses were judged 10
      weeks after the 2nd cycle by performing computed tomography (CT) scans and
      assessing the cytotoxic T lymphocyte (CTL) responses against RNF43 and TOMM34 in
      peripheral lymphocytes. The vaccinations were well tolerated without any serious
      adverse events. CTL responses were induced against both antigens in 8 patients
      and against one antigen in 12 patients, while 1 patient had no CTL response. The
      rate of stable disease was 83%. The group with CTL responses against both
      antigens had the most long-term survivors, followed by the group showing CTL
      responses against one antigen (p=0.0079). The patients with no CTL responses had
      the lowest survival. The safety and immunological responsiveness of the present
      combination therapy suggests that it is clinically beneficial for metastatic
      colorectal cancer. Further clinical trials are warranted.

PMID- 22977473
TI  - Prevalence of type 2 diabetes mellitus in Japanese patients with hepatocellular
      carcinoma.
AB  - The possibility has been raised in a number of cohort and case-control studies
      that diabetes mellitus (DM) may increase the risk of liver cancer, as well as
      that of cancer at other sites. To verify this possibility, we conducted a
      retrospective cohort study to determine the prevalence of type 2 DM in Japanese
      patients with hepatocellular carcinoma (HCC). A total of 1,251 patients with HCC,
      diagnosed at two major liver centers in the Nagasaki area, were consecutively
      recruited and categorized according to the etiology of HCC into four groups: HCC
      B, HCC-C, HCC-BC and HCC-nonBC cases. Type 2 DM was diagnosed on the basis of
      standard criteria. The prevalence rate of HCC-nonBC and HCC-C was significantly
      higher than that of HCC-B, while the prevalence rate of HCC-nonBC was
      significantly higher than that of HCC-C. The prevalence of type 2 DM in HCC-B,
      HCC-C and HCC-nonBC patients under 66 years of age was 11, 31 and 32%,
      respectively, vs. 24, 22 and 40%, respectively, in patients over 66 years of age.
      In patients over 66 years of age, the prevalence of type 2 DM in HCC-B and HCC
      nonBC cases was increased, whereas the prevalence of type 2 DM in HCC-C cases was
      significantly decreased. Our findings indicate that the effects of the
      interaction between type 2 DM and HCV increase the prevalence of HCC.

PMID- 22977474
TI  - Glial fibrillary acidic protein is one of the key factors underlying neuron-like
      elongation in PC12 cells.
AB  - Nerve growth factor (NGF) normally induces the differentiation of PC12 cells into
      a neuron-like phenotype. In this study, we found that exposure of PC12 cells to a
      temperature of 42 degrees C for 24 h significantly decreased NGF-induced neurite
      elongation. Glial fibrillary acidic protein (GFAP) levels were decreased when
      PC12 cells were exposed to the heat stress, while PC12 cells overexpressing the
      gene encoding GFAP showed resistance. Mock-transfected PC12 cells exposed to NGF
      could be cultured for 72 h at 37 degrees C, whereas GFAP-transfected PC12 cells
      exposed to NGF could be cultured for over 100 h. Our results suggest that GFAP is
      necessary for the long-term maintenance of cells with a neuron-like phenotype.

PMID- 22977475
TI  - Route of primary HTLV-1 infection regulates HTLV-1 distribution in reservoir
      organs of infected mice.
AB  - Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia and HTLV
      1-associated myelo-pathy/tropical spastic paraparesis. HTLV-1 is mainly
      transmitted through blood transfusion and breastfeeding, but viral proliferation
      in the body in vivo shortly after transmission is not well understood. To
      investigate whether the route of infection influences the early stages of viral
      proliferation, we inoculated BALB/c mice with MT-2 cells, an HTLV-1-producing
      human T-cell line, via different routes, and evaluated the proviral load and
      humoral immune responses. One month after infection, the provirus was detected in
      most organs of the mice infected intraperitoneally, and substantial proviral
      loads were detected in the peripheral blood and secondary lymphoid organs. In
      contrast, the mice infected intravenously and orally showed low proviral loads,
      and the provirus distribution was limited to the spinal cord among the
      intravenously inoculated mice and to the liver among the perorally inoculated
      mice. Mice infected intraperitoneally also exhibited higher interleukin-2
      production than the mice infected intravenously or orally, or than the uninfected
      control mice, while anti-HTLV-1 antibody titers were comparable between the mice
      infected intraperitoneally and intravenously. These results demonstrate that the
      route of primary HTLV-1 infection influences the establishment of HTLV-1-infected
      cell proliferation and the cell reservoir in mice.

PMID- 22977477
TI  - Therapeutic potential of the TWEAK/Fn14 pathway in intractable gastrointestinal
      cancer.
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the
      TNF superfamily. It has been suggested that it plays a pivotal role in various
      physiological and pathological conditions due to its proinflammatory properties.
      Fibroblast growth-inducible 14 (Fn14) has been identified as a TWEAK receptor. A
      number of studies have suggested that TWEAK-Fn14 interaction results in the
      promotion of apoptosis, cell growth as well as angiogenesis. Although recent
      studies have indicated that TWEAK and Fn14 are expressed in a number of tumor
      lines and tissues, the therapeutic potential of this pathway has yet to be
      elucidated. This study investigated the potential of TWEAK and Fn14 in esophageal
      and pancreatic cancer as novel molecular targets for anti-cancer therapy. TWEAK
      and Fn14 protein expression was evaluated in 43 patients with esophageal cancer
      and 51 patients with pancreatic cancer by immunohistochemistry. As a result,
      either TWEAK or Fn14 expression was observed in 58.1% of the cases with
      esophageal cancer and 74.5% of the cases with pancreatic cancer. Furthermore,
      TWEAK/Fn14 gene expression was identified in the majority of the human esophageal
      and pancreatic cancer cell lines. Therapeutic efficacies of blocking TWEAK and
      Fn14 were evaluated by tumor growth inhibition assay in TWEAK- and Fn14
      expressing human esophageal and pancreatic cancer cell lines. Coculture with anti
      TWEAK or -Fn14 mAb was found to induce a 22-65% cell growth inhibition of these
      cells. Finally, the significant therapeutic effect of targeting this pathway
      under in vivo physiological conditions was confirmed using a murine
      gastrointestinal cancer model. In conclusion, the TWEAK/Fn14 pathway may be
      functional and critical in intractable gastrointestinal cancers. Therefore, TWEAK
      and/or Fn14 may be novel molecular targets for anti-cancer therapy.

PMID- 22977478
TI  - Phase I clinical study of a personalized peptide vaccination available for six
      different human leukocyte antigen (HLA-A2, -A3, -A11, -A24, -A31 and -A33)
      positive patients with advanced cancer.
AB  - The majority of peptide-based cancer vaccines under development are for human
      leukocyte antigen (HLA)-A2- or -A24-positive patients. To overcome this
      limitation, we conducted a phase I clinical study of peptide vaccines designed
      for cancer patients with six different HLA-A types. Eligible patients were
      required to have failed prior standard cancer therapies and to be positive for
      the HLA-A2, -A24 or -A3 (A3, A11, A31 and A33) supertype. Three sets of 8
      candidate peptides (24 peptides in total) were provided for vaccination to HLA
      A2(+), HLA-A24(+) and HLA-A3(+) patients, respectively. Personalization of the
      vaccination peptides from the candidate pool was made by considering the
      patients' HLA types and pre-existing levels of IgGs to the candidate peptides.
      Seventeen patients were enrolled in this study. The peptide vaccinations were
      well tolerated in all patients with no vaccine-related severe adverse events.
      Augmentation of cytotoxic T lymphocyte (CTL) or IgG responses specific to the
      vaccinated peptides was observed in 11 or 10 out of 13 cases tested,
      respectively. This new type of vaccine is recommended for phase II clinical trial
      because of its tolerability and the immune responses to the vaccinated peptides.

PMID- 22977476
TI  - Evaluation of an inflammation-based prognostic score for the identification of
      patients requiring postoperative adjuvant chemotherapy for stage II colorectal
      cancer.
AB  - Recent studies have revealed the Glasgow prognostic score (GPS) to aid in the
      prediction of postoperative outcome in colorectal cancer patients. However,
      whether GPS predicts poor prognosis in curative colorectal cancer patients has
      yet to be ascertained. Furthermore, there is no information on the association
      between GPS and adjuvant chemotherapy in stage II or III colorectal cancer
      patients. A total of 219 patients with stage II and III colorectal cancer were
      included in this trial. The modified GPS (mGPS) defined in this study was
      calculated on the basis of admission data as follows: patients with an elevated
      level of both C-reactive protein (0.5 mg/dl) and hypoalbuminemia (Alb <3.5 mg/dl)
      were allocated a score of 2, and patients showing 1 or none of these blood
      chemistry abnormalities were allocated a score of 1 or 0, respectively. The
      association between the mGPS and clinicopathological findings and survival was
      retrospectively assessed. The mGPS was significantly higher in patients with an
      advanced age, serosal invasion, advanced stage cancer and pre-operative high CEA
      levels. Kaplan-Meier analysis revealed that a higher GPS predicted a higher risk
      of postoperative mortality in stage II and/or III colorectal cancer patients.
      Multivariate analyses revealed that the mGPS was the most sensitive predictor of
      postoperative mortality in stage II/III or stage II, respectively. The prognosis
      of stage II patients with a higher mGPS was as favorable as that of patients with
      a lower mGPS when adjuvant chemotherapy was undertaken. Pre-operative mGPS is
      considered to be a useful predictor of postoperative mortality in patients with
      stage II and/or III colorectal cancer, independently of the CEA test or TNM
      system. Postoperative adjuvant chemotherapy may be recommended for stage II
      colorectal cancer patients with a high mGPS.

PMID- 22977479
TI  - Chemical and biological analysis of active free and conjugated bile acids in
      animal bile using HPLC-ELSD and MTT methods.
AB  - The aim of the present study was to determine the chemical composition and in
      vitro cytotoxic activity of seven bile samples and bile acids using the high
      performance liquid chromatography (HPLC)-evaporative light scattering detector
      (ELSD) method. Free and conjugated bile acid standards were used to identify and
      quantify the chemical components of the seven animal bile samples. The MTT assay
      was used to determine the cytotoxic effect of the animal bile samples and the
      free and conjugated bile acids on hepatocellular carcinoma MHCC97-L cells.
      Chemical analysis revealed that the bile samples from the different animals
      shared little similarity in terms of their composition. A cell viability assay
      revealed that cattle bile, as well as its major components, DCA, CDCA and TCDCA,
      exhibited a marked cytotoxic effect on the hepatocellular carcinoma MHCC97-L
      cells. The bear bile samples that originated from the Asian black bear and the
      American black bear contained a unique component, TUDCA, which distinguished them
      from the other animal bile, though their inhibitory action on MHCC97-L cells was
      not markedly distinct. The present study reveals that cattle bile may be a
      potential alternative to bear bile for hepatocarcinoma therapy.

PMID- 22977480
TI  - Patient outcome prediction using multiple biomarkers in human melanoma: A
      clinicopathological study of 118 cases.
AB  - The application of biomarkers in melanoma prognosis has been well recognized.
      However the ability of a single biomarker to predict melanoma patient outcome is
      usually limited. We previously examined the expression of ten biomarkers (Bim,
      BRG1, BRMS1, CTHRC1, ING4, NQO1, NF-kappaB-p50, PUMA, SNF5 and SOX4) in
      melanomas. To assess the value of a combined multiple biomarker system in
      melanoma prognosis, we compared the expression of each biomarker between various
      stages of melanoma, and determined the best combination of biomarkers for
      melanoma prognosis. Although the expression of six biomarkers (Bim, BRMS1, ING4,
      NQO1, PUMA and SOX4) was significantly decreased in AJCC III-IV stages of
      melanoma compared to AJCC I-II stages, the combined 6-biomarker index score
      exhibited higher variations than any individual biomarker in the same comparison.
      Moreover, the 6-biomarker index score was correlated with melanoma thickness,
      location and subtype, and predicted the outcome of melanoma patients more
      accurately than the individual biomarkers. Multivariate Cox regression analysis
      demonstrated that the 6-biomarker index score is an independent prognostic factor
      for melanoma. In conclusion, our study suggests that a multi-biomarker system
      test is valuable for improved outcome prediction in melanoma patients and for the
      development of novel therapeutic strategies.

PMID- 22977481
TI  - Frequent expression of MAGE1 tumor antigens in bronchial epithelium of smokers
      without lung cancer.
AB  - Melanoma antigens (MAGE) are frequently expressed in lung cancer and are
      promising targets of anticancer immunotherapy. Our preliminary data suggested
      that MAGE may be expressed during early lung carcinogenesis, raising the
      possibility of targeting MAGE as a lung cancer prevention strategy. The purpose
      of this study was to investigate MAGE activation patterns in the airways of
      chronic smokers without lung cancer. MAGE-A1, -A3 and -B2 gene expression was
      determined in bronchial brush cells from chronic former smokers without lung
      cancer by reverse transcription-PCR (RT-PCR). The results were correlated with
      clinical parameters. The 123 subjects had a median age of 57 years, a median of
      40 pack-years smoking history, and had quit smoking for at least one year prior
      to enrollment. Among the subjects, 31 (25%), 38 (31%), and 46 (37%) had
      detectable MAGE-A1, -A3 and -B2 expression, respectively, in their bronchial
      brush samples. Expression of MAGE-A1 and -B2 positively correlated with pack
      years smoking history (P=0.03 and 0.03, respectively). The frequency of
      expression did not decrease despite a prolonged smoking cessation period. In
      conclusion, MAGE-A1, -A3 and -B2 genes are frequently expressed in the bronchial
      epithelial cells of chronic smokers without lung cancer, suggesting that chronic
      exposure to cigarette smoke activates these genes even before the malignant
      transformation of bronchial cells in susceptible individuals. Once activated, the
      expression persists despite long-term smoking cessation. These data support the
      targeting of MAGE as a novel lung cancer prevention strategy.

PMID- 22977482
TI  - Antioxidant activity and antiapoptotic effect of Asparagus racemosus root
      extracts in human lung epithelial H460 cells.
AB  - The present study examined the antioxidant activity and protective effect of
      extracts from Asparagus racemosus roots against Lipofectamine-induced apoptosis.
      Five fractions from a successive extraction process ranging from non-polar to
      more polar solvents were obtained. The total saponin content as a marker in terms
      of diosgenin equivalent value of the root extracts was found to be in the range
      of 240-420 MUg/mg extract, with higher values for the ethanol and aqueous
      fractions. The antioxidant activity measured using the DPPH method in terms of
      mean effective concentration (EC(50)) of the aqueous fraction was found to be 600
      MUg/ml as compared to 1.5 MUg/ml of ascorbic acid. It is proposed that Asparagus
      racemosus root extracts effectively inhibit Lipofectamine-induced apoptosis by
      their protective effect, and may serve as an advantageous alternative option for
      gene delivery.

PMID- 22977483
TI  - IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre
      cancerous and cancer lesions.
AB  - Human papillomavirus (HPV) plays a crucial role in cervical cancer etiology.
      However, not all HPV-infected women develop cancer, indicating that additional
      cellular factors facilitate carcinogenesis. The aim of this study was to analyze
      the expression profile of insulin-like growth factor 1 (IGF1) isoforms in the
      context of FOX2, SP1 and IGF1 receptor (IGF1R) expression during HPV-dependent
      cervical carcinogenesis. One hundred and nine epithelial tissue samples from
      women with pre-cancerous and cancer lesions of the cervix were analyzed. HPV DNA
      was identified by PCR, and real-time PCR was used to quantify the expression
      levels of the analyzed genes. All IGF1 mRNA splicing isoforms were up-regulated
      in pre-cancerous cells, and a shift in the balance towards mitogenic IGF1Eb was
      observed in the cancer samples. IGF1 expression was controlled mainly by the P1
      promoter, and an increase in P2 usage was observed in the cancer. Correlations
      between IGF1 mRNA splicing isoforms and the FOX2 splicing factor, as well as
      P1/P2 activity and SP1 transcription factor expression levels were detected. No
      correlation was observed between the expression of IGF1 and its receptor IGF1R.
      Our results suggest that IGF1, in particular its splicing profile, may be an
      additional prognostic factor in cervical carcinogenesis.

PMID- 22977484
TI  - Metastasis tumour suppressor-1 and the aggressiveness of prostate cancer cells.
AB  - Previous studies have suggested that metastasis tumour suppressor-1 (MTSS1) plays
      a key role in cancer metastasis. Firstly, in this study we assessed MTSS1
      expression levels in prostate cancer cell lines to reveal any changes in cell
      properties. Secondly, we aimed to clarify the cellular function of MTSS1 in
      prostate cancer cells. MTSS1 expression levels were assessed in different types
      of cancer cell lines through the RT-PCR analysis technique. The influence of
      MTSS1 was further examined via biological overexpression and knockdown in the
      prostate cancer cell lines. Two prostate cell lines were chosen for either
      knockdown or overexpression of the MTSS1 gene. The overexpression of MTSS1 in PC
      3 human prostate cancer cells significantly suppressed the migratory, growth and
      adherence properties of the cells (p<0.01). By contrast, the knockdown of MTSS1
      in DU-145 human prostate cancer cells dramatically enhanced these properties
      (p<0.001). We concluded that MTSS1 demonstrates the ability to play a role in
      controlling the metastatic nature of prostate cancer cells.

PMID- 22977485
TI  - Aberrant expression and function of death receptor-3 and death decoy receptor-3
      in human cancer.
AB  - Death receptor-3 (DR3) and death decoy receptor-3 (DcR3) are both members of the
      tumour necrosis factor receptor (TNFR) superfamily. The TNFR superfamily contains
      eight death domain-containing receptors, including TNFR1 (also called DR1), Fas
      (also called DR2), DR3, DR4, DR5, DR6, NGFR and EDAR. Upon the binding of these
      receptors with their corresponding ligands, the death domain recruits various
      proteins that mediate both the death and proliferation of cells. Receptor
      function is negatively regulated by decoy receptors (DcR1, DcR2, DcR3 and OPG).
      DR3/DcR3 are a pair of positive and negative players with which vascular
      endothelial growth inhibitor (VEGI) interacts. VEGI has been suggested to be a
      potential tumour suppressor. The inhibitory effects of VEGI on cancer are
      manifested in three main areas: a direct effect on cancer cells, an anti
      angiogenic effect on endothelial cells, and the stimulation of dendritic cell
      maturation. A recent study indicated that DR3 may be a new receptor for E
      selectin, which has been reported to be associated with cancer metastasis. DcR3
      is a soluble receptor, highly expressed in various tumours, which lacks an
      apparent transmembrane segment, prevents cytokine response through ligand binding
      and neutralization, and is an inhibitor of apoptosis. DcR3 serves as a decoy
      receptor for FasL, LIGHT and VEGI. The cytokine LIGHT activates various anti
      tumour functions and is expected to be a promising candidate for cancer therapy.
      Certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing
      DcR3, which blocks FasL function. DR3/DcR3 play profound roles in regulating cell
      death and proliferation in cancer. The present review briefly discusses DR3/DcR3
      and attempts to elucidate the role of these negative and positive players in
      cancer.

PMID- 22977486
TI  - Maintenance therapy in ovarian cancer: Molecular basis and therapeutic approach.
AB  - Ovarian cancer has the highest mortality rate among gynaecological tumours
      despite the fact that the majority of patients with advanced disease achieve
      complete remission after first-line surgery and chemotherapy. Unfortunately,
      disease recurrence occurs in the majority of patients and second-line treatments
      are not curative. Clearly, the persistence of dormant and drug-resistant cells
      after front-line treatments results in the inability to cure the disease. The
      identification of cancer-initiating cells or cancer stem cells as key players in
      the development of recurrence has opened up a novel field of research aimed at
      identifying additional innovative therapeutic approaches. Strategies of
      maintenance therapy to extend the survival of patients have been studied, but to
      date no overall survival benefit has been detected. Currently, numerous clinical
      trials have just been completed or are ongoing involving patients achieving a
      complete clinical response after first-line chemotherapy in order to evaluate the
      efficacy of different therapeutic approaches in terms of disease-free survival
      and overall survival. At the 2010 ASCO meeting, the first positive results of a
      phase III clinical trial in this setting were presented: bevacizumab (15 mg/kg
      i.v. every 21 days) added to first-line chemotherapy and continued for an
      additional 15 cycles was found to prolong progression-free survival of 3.8 months
      in comparison to 6 cycles of chemotherapy alone or only 6 cycles of chemotherapy
      plus bevacizumab. In addition, positive results were announced for a second phase
      III trial testing bevacizumab in the same setting, but at half dose. The final
      assessment of the overall clinical benefit and the approval of bevacizumab in
      maintenance therapy by regulatory agencies is expected to be positive, as are the
      final results of abagovomab phase III trial MIMOSA, another antibody-based
      therapy tested as a maintenance treatment for advanced ovarian cancer patients.
      Encouraging preliminary results confirming the safety profile and the immunogenic
      activity of abagovomab were presented at the last ASCO meeting. The final results
      are expected to be released in the first half of 2011.

PMID- 22977487
TI  - Prevalence of serum vitamin D deficiency and insufficiency in cancer: Review of
      the epidemiological literature.
AB  - Vitamin D deficiency has been found to be associated with a variety of cancers,
      including prostate, multiple myeloma, colorectal and breast cancer. Several
      studies have shown vitamin D levels to have an inverse relation with cancer
      mortality, while others have considered it a potential risk factor. Vitamin D is
      believed to influence cancer prevalence, risk and survival; hence the need to
      assess vitamin D levels in cancer. Although numerous studies have been conducted
      to demonstrate vitamin D deficiency as a risk factor for cancer, relatively few
      have studied its prevalence. Moreover, studies estimating prevalence differ from
      each other, with respect to study population, sample size, study design,
      definition of vitamin D deficiency used and method of vitamin D assessment (with
      most studies limited to one particular type of cancer with relatively small
      sample sizes). Therefore, we qualitatively reviewed the epidemiological evidence
      in the oncology literature on the prevalence of vitamin D deficiency and
      insufficiency as measured by serum vitamin D concentrations.

PMID- 22977488
TI  - Lactate dehydrogenase production in hepatocytes is increased at an early stage of
      acute liver failure.
AB  - Although the mechanism involved in acute liver failure (ALF) has not yet been
      clarified, microcirculatory disturbance in the liver appears to play a pivotal
      role in the progression of this disease. To confirm the existence of hepatic
      hypoxic conditions, we evaluated the amounts of lactate dehydrogenase (LDH) in
      hepatocytes, since its production increases under low oxygen concentrations.
      Histological examination was performed in 7 patients with ALF. All 7 patients
      underwent a liver biopsy during the acute phase of ALF, and 4 of them underwent a
      second biopsy during the recovery phase. The obtained samples were
      immunohistochemically stained with anti-LDH5 and anti-CD-68 antibodies. As
      controls, we examined samples from patients with acute hepatitis, chronic
      hepatitis and liver cirrhosis. The production of LDH by hepatocytes and the
      number of CD-68 positive macrophages were markedly increased at the acute phase
      of ALF, and both of these effects abruptly decreased during the recovery phase.
      By contrast, most of the samples from the patients with chronic hepatitis and
      acute hepatitis showed slightly any increase in LDH staining. In cirrhotic
      patients, partially elevated LDH production was observed mainly around the
      central vein, but the staining intensity was less compared to that in ALF
      patients. Our findings indicate that hepatic hypoxic conditions exist in ALF at
      the acute phase and seem to closely correlate with macrophage overactivation in
      the liver. We speculate that microcirculatory disturbance may be a key process in
      the development and progression of ALF.

PMID- 22977489
TI  - Whole rat DNA array survey for candidate genes related to hypertension in kidneys
      from three spontaneously hypertensive rat substrains at two stages of age and
      with hypotensive induction caused by hydralazine hydrochloride.
AB  - Clarification of the genetic nature and more effective care for hypertension are
      required, given the high incidences of cardiovascular and cerebrovascular
      mortality. Thus, we surveyed candidate genes for hypertension with rat whole gene
      DNA microarrays using three novel methods. Gene expression analyses were
      conducted as follows: Method 1, three types of spontaneously hypertensive rat
      (SHR) substrains, SHR, stroke-prone SHR (SHRSP) and malignant type of SHRSP (M
      SHRSP) were used and compared to normotensive Wistar Kyoto rats; Method 2, the
      expressed genes between rats of different ages were compared for different blood
      pressures; and Method 3, genes that were expressed in rats treated with or
      without an acute hypotensive stimulus, the antihypertensive hydralazine
      hydrochloride, were compared. This approach identified dozens of genes, including
      Dusp15, Cyp8b1, Armc 3, Gtpbp4, Mettl2, Mapk14, Prkar2b, frame 12, Anxa13, Ephx2,
      Myr8 and Pcdh9 by Method 1; Cyp2C and Atp12a by Method 2; and Kcnc3, Vnn1,
      TC560558 and Gabrq and a number of unknown genes by Methods 2 and 3, as probable
      candidate genes for hypertension in SHR substrains. Ephx2 was previously reported
      as a candidate gene in SHRs; however other genes were identified for the first
      time in this study. Since it was not always possible to completely demonstrate
      that these genes are responsible for hypertension in SHRs, further research into
      true candidate genes that participate in the genesis of hypertension in SHR
      substrains is warranted.

PMID- 22977490
TI  - Cyclin D1 predicts the prognosis of advanced serous ovarian cancer.
AB  - We previously reported that cyclin E (CCNE1) amplification is strongly associated
      with resistance to treatment in serous ovarian cancer by high-resolution
      oligonucleotide copy number analysis. Dysregulation of cell cycle control has
      been implicated as the key event in human oncogenesis, and aberrant expression of
      G1-S phase-related genes in particular has been reported in epithelial ovarian
      cancer (EOC). Nevertheless, there are conflicting results concerning the
      prognostic values of these abnormalities in EOC. This study focused on advanced
      serous EOC cases and investigated the association between the expression of G1-S
      phase-regulatory proteins and clinicopathological parameters. The utility of
      these proteins as prognostic factors was assessed, and whether these targets
      reflect chemoresistance of advanced serous EOC was investigated. A total of 66
      patients treated by primary surgery were evaluated in this study.
      Immunohistochemical analysis for cyclin D1, pRb, p16, p53, p27(Kip1),
      p21(Waf1/Cip1) and cyclin E was performed on formalin-fixed tissue sections
      collected from primary surgical specimens. The correlations between the
      expression of these proteins and the clinicopathological parameters, including
      progression-free survival (PFS), overall survival (OS) and chemosensitivity, were
      examined. Upon univariate analysis, overexpression of cyclin D1 was positively
      correlated with reduced PFS (p=0.00062) and OS (p=0.00037). Reduced expression of
      p27(Kip1) was associated with shorter OS (p=0.064). Upon multivariate analysis,
      overexpression of cyclin D1 (p=0.0019), reduced expression of p27(Kip1) (p=0.042)
      and residual tumor volume (p=0.0092) were identified as independent predictors of
      OS. Overexpression of cyclin D1 (p=0.011) as well as residual tumor volume
      (p=0.006) were significantly associated with first-line chemosensitivity. In
      advanced serous EOC, overexpression of cyclin D1 contributed largely to poor
      prognosis, and this may have been in part mediated by chemoresistance. Cyclin D1
      is a possible target for overcoming the refractory nature of advanced serous EOC.

PMID- 22977491
TI  - Up-regulated Annexin A1 expression in gastrointestinal cancer is associated with
      cancer invasion and lymph node metastasis.
AB  - Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved
      in anti-inflammatory effects, regulation of cellular differentiation,
      proliferation and apoptosis. In the present study, we investigated the expression
      of ANXA1 in gastric and colon cancer, and analyzed the relationship between ANXA1
      expression and clinicopathological factors. ANXA1 mRNA expression in gastric and
      colon cancer tissues was not significantly changed compared to that in normal
      tissues. When ANXA1 protein expression was evaluated by immunohistochemical
      staining, ANXA1 expression was observed in 76 of 135 cases of gastric cancer
      (56.3%), and correlations were found between ANXA1 expression and depth of wall
      invasion (P<0.001), lymphatic invasion (P=0.023), venous invasion (P=0.002),
      lymph node metastasis (P=0.001) and UICC stage (P<0.001). Disease-specific
      survival rate was significantly lower in cases with ANXA1 expression compared to
      that in cases without (P=0.0053). In colon cancer, ANXA1 expression was detected
      in 61 of 210 cases (29.0%) and correlations were found with gender (P=0.038),
      lymphatic invasion (P=0.011), venous invasion (P=0.023), lymph node metastasis
      (P=0.042) and UICC stage (P=0.041). The disease-specific survival rate tended to
      be lower in cases with ANXA1 expression, although the differences were not
      statistically significant (P=0.6984). Our results indicate that up-regulated
      ANXA1 expression is involved in cancer invasion and lymph node metastasis.
      Furthermore, high levels of ANXA1 expression were implicated in poor prognosis of
      patients. ANXA1 may be applicable as a prognostic biomarker in gastric and colon
      cancer, and a potential target for treatment.

PMID- 22977492
TI  - Evaluation of the effect of oxidative stress on articular cartilage in
      spontaneously osteoarthritic STR/OrtCrlj mice by measuring the biomarkers for
      oxidative stress and type II collagen degradation/synthesis.
AB  - To investigate the involvement of oxidative stress in the pathogenesis of
      osteoarthritis (OA), we evaluated the relationship between oxidative stress and
      articular cartilage degradation by measuring the serum levels of malondialdehyde
      (MDA, an oxidative stress marker), CTX-II (a type II collagen degradation marker)
      and CPII (a type II collagen synthesis marker) in obese and hyperlipidemic
      STR/Ort (STR) and control CBA mice. Seven-week-old osteoarthritic STR male mice
      (n=10) and control CBA male mice (n=10) were fed standard laboratory food ad
      libitum. At 35 weeks of age, the mice were sacrificed, and the serum levels of
      MDA, CTX-II and CPII were determined. Furthermore, histopathological changes were
      evaluated in the knee joints. Most of the STR mice spontaneously developed OA (18
      of the 20 knees). By contrast, the CBA mice developed OA in only 4 of the 20
      knees. Importantly, the serum levels of MDA, CTX-II and CPII were elevated to a
      greater extent in the STR mice compared to levels in the CBA mice. Notably, the
      level of MDA was correlated with that of CTX-II, but not of CPII. Moreover, the
      MDA levels were significantly correlated with the serum lipid (total cholesterol
      and triglyceride) levels as well as body weight. Together these observations
      suggest that oxidative stress is likely involved in the degradation of type II
      collagen in articular cartilage, thereby possibly contributing to the development
      of OA in obese and hyperlipidemic STR mice.

PMID- 22977493
TI  - Prognostic value of co-expression of STAT3, mTOR and EGFR in gastric cancer.
AB  - Signal transducer and activator of transcription 3 (STAT3), the mammalian target
      of rapamycin (mTOR) and epidermal growth factor receptor (EGFR), proteins that
      mediate intracellular signaling related to cell growth, proliferation and
      differentiation, have received considerable interest as possible targets for
      cancer treatment. We examined whether the expression of STAT3, mTOR and EGFR
      correlates with clinicopathological features and patient outcome in gastric
      cancer. Tumor samples were obtained from 126 patients with gastric
      adenocarcinomas who underwent a radical gastrectomy between 1999 and 2002. The
      expression of phosphorylated STAT3 (p-STAT3), p-mTOR and EGFR was analyzed by
      immunohistochemical staining. The relations of these to clinicopathological
      factors and outcomes were assessed. The expression of p-STAT3 p-mTOR and EGFR
      positively correlated with the following variables related to tumor progression:
      the depth of tumor invasion (T1 vs. T2-4; p<0.001, p=0.036 and p<0.001,
      respectively), lymph node involvement (p=0.008, p=0.027 and p=0.007) and tumor
      stage (I vs. II-IV; p<0.001, p=0.041 and p<0.001). The expression of p-STAT3 and
      EGFR was significantly related to distant metastasis and recurrence (p=0.001 and
      p=0.039), as well as significantly poorer disease-specific survival (DSS;
      p=0.0018 and p=0.026). The expression of p-STAT3 was a marginally non-significant
      prognostic factor for DSS (hazard ratio=2.0, 95% CI 0.91-4.5, p=0.082).
      Increasing expression of p-STAT3, p-mTOR and EGFR was associated with
      progressively worse DSS. Interactions among p-STAT3, p-mTOR and EGFR may play an
      important role in tumor progression and outcomes in patients with gastric cancer.

PMID- 22977494
TI  - Pathological tumor response to neoadjuvant chemotherapy using anthracycline and
      taxanes in patients with triple-negative breast cancer.
AB  - Although triple-negative breast cancer (TNBC) is associated with a poor
      prognosis, recent reports have indicated that a higher proportion of TNBC
      patients shows a pathological complete response (pCR) to neoadjuvant chemotherapy
      (NAC) than is the case for non-TNBC patients. The aim of this study was to
      identify markers that predict pCR to NAC in TNBC patients, and to clarify
      prognostic factors that affect the outcome of TNBC patients with residual disease
      (RD) after NAC. Among 44 TNBC patients who received anthracycline- and taxane
      based combination NAC, we analyzed the relationship between pathological response
      and clinicopathological characteristics, including immunohistochemical parameters
      (cytokeratin 5/6, epidermal growth factor receptor, Ki-67, p53, breast cancer
      susceptibility protein 1 and topoisomerase IIalpha). We also assessed the
      prognostic impact on patients with RD by analyzing the correlation between
      disease-free survival (DFS) and clinicopathological parameters. Sixteen patients
      (36%) achieved a pCR and log-rank test showed that these patients had a
      significantly more favorable outcome than patients with RD (DFS, P=0.00184;
      overall survival, P=0.0080). Among the clinicopathological parameters examined,
      none was correlated with pathological response, with the exception of p53.
      Patients with immunohistochemical overexpression of p53 more frequently achieved
      a pCR than those without p53 overexpression (P=0.0484). In the patients with RD,
      the Cox proportional hazards model showed that the presence of lymphovascular
      invasion was significantly associated with shorter DFS (hazard ratio, 13.333; 95%
      CI 1.587-111.111; P=0.0171). p53 overexpression may be a key predictor of a
      favorable response to NAC. Since patients with RD, particularly those positive
      for lymphovascular invasion, had an extremely poor outcome, novel therapeutic
      approaches for these patients are warranted.

PMID- 22977495
TI  - Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5
      fluorouracil for patients with postoperative liver metastases from pancreatic
      cancer.
AB  - Hepatic metastasis is a common cause of treatment failure after curative
      resection of pancreatic cancer. We report a pilot study of hepatic arterial
      infusion (HAI) chemotherapy with gemcitabine and 5-fluorouracil (5-FU) for
      postoperative liver metastases from pancreatic cancer. Five patients who had
      undergone curative resection of liver metastases from pancreatic cancer received
      HAI of gemcitabine and 5-FU between October 2008 and September 2010 at Kanazawa
      University Hospital. Gemcitabine at a dose of 800 mg was infused over 30 min via
      a bedside pump. After gemcitabine administration, 250 mg of 5-FU was infused
      continuously over 24 h on days 1-5, comprising one cycle of therapy. These
      treatment cycles were continued biweekly. In the evaluation according to RECIST
      criteria, a partial response was obtained in 2 of the 5 cases, with stable
      disease being achieved in the remaining 3 cases (response rate, 100%). In 4 of
      the 5 cases, a decrease in serum tumor marker CA19-9 was observed after 10 HAI
      treatment cycles. The median time to treatment failure was 10 months (range 3
      17). As to adverse events, leukocytopenia was grade 3 in 1 of 4 affected cases
      and all 5 were anemic, although 4 of the 5 cases had anemia prior to HAI therapy.
      Grade 2 thrombocytopenia was observed in 2 cases. No nonhematologic events, such
      as nausea, diarrhea, liver injury and neuropathy, occurred. There were no life
      threatening toxicities, but 4 cases (80%) developed catheter complications, and
      the HAI catheter and subcutaneous implantable port system had to be removed. HAI
      delivers high doses of chemotherapeutic agents directly into tumor vessels,
      producing increased regional levels with greater efficacy and a lower
      incidence/severity of systemic side effects. In conclusion, HAI chemotherapy is
      useful and safe for the treatment of malignancies confined to the liver.

PMID- 22977496
TI  - Decreased type III collagen expression in human uterine cervix of prolapse uteri.
AB  - The precise mechanism of prolapse uteri is not fully understood. There is
      evidence to suggest that abnormalities of collagen, the main component of
      extracellular matrix, or its repair mechanism, may predispose women to prolapse.
      To investigate the characteristic structure of human uterine cervix of patients
      with prolapse uteri, various types of collagen expression in the uterine cervix
      tissues of the prolapse uteri were compared to those of normal uterine cervix.
      After informed consent, 36 specimens of uterine cervical tissues were obtained at
      the time of surgery from 16 postmenopausal women with prolapse uteri (stage III
      IV by the Pelvic Organ Prolapse Quantification examination) and 20 postmenopausal
      women without prolapse uteri (control group). Collagens were extracted from the
      uterine cervix tissues by salt precipitation methods. The relative levels of
      various collagens were evaluated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The uterine cervix was longer in the patients with prolapse
      uteri than those of postmenopausal controls without prolapse uteri. The ratios of
      type III to type I collagen in the uterine cervical tissues were significantly
      decreased in the prolapse uteri, as compared to those of the postmenopausal
      uterine cervix without prolapse. These results suggest that decreased type III
      collagen expression may play an important role in determing the physiology and
      structure of the uterine cervix tissues of prolapse uteri.

PMID- 22977497
TI  - Lack of evidence to support the association of polymorphisms within the TNFSF4
      gene and coronary heart disease in a Chinese Han population.
AB  - Coronary heart disease (CHD) is a complex disorder resulting from the interaction
      of a number of genetic and environmental factors. Increasing evidence has shown
      that OX40 ligand (OX40L), also known as tumor necrosis factor superfamily member
      4 (TNFSF4), plays a key role in the pathogenesis of atherosclerosis. However,
      there have been inconsistent reports in various populations, and further studies
      are required to clarify this issue. A gene-based association study was conducted
      using five single-nucleotide polymorphisms (SNPs) reported in previous studies.
      The five SNPs (rs1234314, rs45454293, rs3850641, rs1234313 and rs3861950) were
      genotyped in 547 unrelated CHD patients and 601 healthy controls in a case
      control study using polymerase chain reaction and restriction fragment length
      polymorphism. rs1234314, rs3850641 and rs3861950 were further genotyped in an
      additional 512 cases and 520 controls using the TaqMan SNP genotyping method. A
      possible relationship between the five SNPs and the severity of CHD was
      investigated. The results revealed no significant association between the TNFSF4
      polymorphism and CHD. In addition, the stratified analysis of genotypic and
      allelic frequencies showed no association between the TNFSF4 polymorphism and CHD
      in either gender. Finally, no significant correlation between the TNFSF4
      polymorphism and CHD severity was detected. These findings do not support a role
      of the TNFSF4 gene in CHD pathogenesis in the Chinese Han population.

PMID- 22977498
TI  - Prostatic relaxation induced by loperamide is mediated through activation of
      opioid MU-2 receptors in vitro.
AB  - The merit of opioid MU-receptor activation in the improvement of benign prostatic
      hyperplasia (BPH) remains obscure. In the present study, we used loperamide to
      identify the subtype of opioid MU-receptors involved in prostatic relaxation and
      investigate the possible mechanism of this relaxation. Prostate strips were
      isolated from 12-week-old male Wistar rats for identification of isometric
      tension. The prostate strips were precontracted with either 1 MUmol/l
      phenylephrine or 50 mmol/l KCl. The decrease in muscle tone (relaxation) was then
      characterized after cumulative administration of loperamide (0.1 to 10 MUmol/l)
      into the organ bath for the concentration-dependent study. Pretreatment with
      specific blockers or antagonists was carried out to compare the changes in
      loperamide-induced relaxation. Loperamide produced a marked relaxation in the
      isolated prostates precontracted with phenylephrine or KCl in a dose-dependent
      manner. This relaxation was abolished by cyprodime, a selective opioid MU
      receptor antagonist, but was not modified by naloxonazine at a dose sufficient to
      block the opioid MU-1 receptors. Treatment with an agonist for opioid MU-1
      receptors also failed to modify the muscle tone. Moreover, the relaxation by
      loperamide was attenuated by glibenclamide at a dose sufficient to block ATP
      sensitive K(+) channels. In addition, this action of loperamide was abolished by
      protein kinase A (PKA) inhibitor and enhanced by the inhibitor of
      phosphodiesterase for cyclic AMP (cAMP). Our results suggest that loperamide
      induces prostatic relaxation through activation of opioid MU-2 receptors via the
      cAMP-PKA pathway to open ATP-sensitive K(+) channels.

PMID- 22977499
TI  - Immunohistochemical analysis of collagen expression in uterine leiomyomata during
      the menstrual cycle.
AB  - To investigate the possible involvement of collagen in the characteristic
      features of human leiomyoma, type I, III and IV collagen expression was
      determined at the protein level in normal myometrium and leiomyoma tissues
      throughout the menstrual cycle. The tissues were obtained from 40 pre-menopausal
      women (29-53 years of age) at various stages of the menstrual cycle who were
      undergoing abdominal hysterectomy for symptomatic uterine leiomyoma.
      Immunohistochemical staining was performed with specific monoclonal antibodies
      against type I, III and IV collagen in the leiomyoma and the myometrial tissues.
      Immunohistochemical analysis revealed that type I collagen expression was
      increased in the leiomyoma tissues at the protein level as compared to that in
      the normal myometrium tissues throughout the menstrual cycle. These results
      suggest that increased expression of type I collagen plays a key role in the
      pathogenesis of uterine leiomyoma.

PMID- 22977500
TI  - Quality of life of lung cancer patients receiving outpatient chemotherapy.
AB  - An increasing number of cancer patients receive outpatient chemotherapy as an
      alternative to inpatient chemotherapy. The aim of this study was to investigate
      whether quality of life (QOL) during outpatient chemotherapy was better than QOL
      prior to hospital discharge, and to explore possible related factors prior to
      hospital discharge that affected the QOL of lung cancer patients who received
      outpatient chemotherapy. Lung cancer inpatients who were scheduled for outpatient
      chemotherapy were assessed two times (prior to hospital discharge and during
      outpatient chemotherapy) using the Functional Assessment of Cancer Therapy-Lung
      and Hospital Anxiety and Depression Scale. A total of 40 patients completed all
      assessments, both prior to hospital discharge and during outpatient chemotherapy.
      In the present study, QOL during outpatient chemotherapy was not significantly
      different when compared with the QOL prior to hospital discharge, and predictors
      prior to hospital discharge for a better QOL of patients during outpatient
      chemotherapy included better social, emotional and physical well-being. These
      results suggest that medical staff, in particular those involved in outpatient
      chemotherapy, need to recognize social and emotional as well as physical well
      being prior to hospital discharge, regardless of cancer-related factors and the
      personal characteristics of the patients.

PMID- 22977501
TI  - High expression levels of erythropoietin and its receptor are not correlated with
      shorter survival in human glioblastoma.
AB  - Erythropoietin (EPO) is used to treat anemia in neoplastic disease. EPO also
      exerts neuroprotective effects on neuronal cells, making a prophylactic use
      against the neurocognitive effects of radiochemotherapy probable. However,
      EPO/EPO-receptor (EPOR) signalling has been also detected in glioblastoma cells.
      Data collected in vitro and in vivo show conflicting results on the effect of EPO
      on malignant gliomas. The association between EPO and EPOR expression and the
      prognosis of human glioblastomas was analyzed. Probes of human glioblastomas with
      complete documentation of clinical course and treatment were assessed by
      immunohistochemistry for the expression of EPO and EPOR (n=80). Using univariate
      and multivariate survival analysis, the association with age, gender, radiation,
      chemotherapy and extent of resection was determined. High levels of EPOR were
      correlated with a median survival advantage of 7 months (p<0.01). By univariate,
      but not multivariate, analysis, high levels of EPO and EPOR were associated with
      a significant prolongation of 7 months median survival when compared to low
      levels of both molecules. In patients treated with radiochemotherapy adjuvant to
      surgery, the median survival was 6.5 months longer in patients with high levels
      of EPOR (p<0.04). According to previous studies, longer patient survival is
      associated with EPOR expression. Therefore, EPO appears to be safe for the
      treatment of anemia in glioblastoma patients. However, a prophylactic use, i.e.,
      for neuroprotection, is not recommended in light of the functional studies
      described in the literature.

PMID- 22977502
TI  - Valproate inhibits colon cancer growth through cell cycle modification in vivo
      and in vitro.
AB  - Valproate (VPA) is a well-characterized histone deacetylase inhibitor with anti
      neoplastic properties. We analyzed the growth blocking effects and the molecular
      mode of action of this compound in colorectal cancer cells in vitro and in vivo.
      Caco-2, SW-480, CX-1 or WIDR cell lines were exposed to VPA (0.25-2 mM) for
      various time periods. Cell growth, cell cycle progression and apoptosis were
      analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide dye
      reduction assay and flow cytometry. Cell cycle- and apoptosis-regulating proteins
      and histone acetylation were assessed by Western blotting. In vivo tumor growth
      and regulating protein expression under VPA were investigated in a subcutaneous
      xenograft tumor model. VPA inhibited the growth of all cell lines with cell cycle
      arrest paralleled by the up-regulation of H3 and H4 acetylation. In vivo tumor
      growth was substantially depressed by VPA (200 mg/kg bw). Cell cycle proteins
      (cdk1, cdk2, cdk4, cyclin D, cyclin E, p19, p21 and p27) were differentially
      altered by VPA. Predominantly cdk1 was decreased and p27 was up-regulated in all
      models. Apoptosis-related proteins were altered in vivo with up-regulation of bax
      and down-regulation of bcl-2. VPA exerts anti-neoplastic activity in colorectal
      tumor cell lines in vitro and in vivo by altering cell cycle regulation.

PMID- 22977503
TI  - Enhanced peroxisomal beta-oxidation metabolism in visceral adipose tissues of
      high-fat diet-fed obesity-resistant C57BL/6 mice.
AB  - This study aimed to investigate the potential mechanisms of natural resistance to
      high-fat diet-induced obesity. Four-week-old C57BL/6 mice were fed a high-fat
      diet for 6 weeks and were then designated as high-fat diet-fed obesity-prone
      (HOP) and obesity-resistant (HOR) animals. Their blood biochemistry was
      evaluated, and visceral adipose tissue samples were subjected to proteomic,
      Western blot and quantitative real-time PCR (q-PCR) analyses. The HOR mice showed
      reduced visceral fat weight and size, as well as lowered serum lipid and leptin
      levels. Proteomic analysis showed that enoyl coenzyme A hydratase 1, peroxisomal
      (Ech1) expression was significantly increased in their visceral adipose tissues.
      Moreover, other proteins, such as alpha-tropomyosin, myosin light chain, urine
      nucleoside phosphorylase and transgelin, were also significantly increased.
      Furthermore, q-PCR analysis showed that the expression of acyl-CoA oxidase 1
      palmitoyl, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA
      thiolase responsible for peroxisomal beta-oxidation was also up-regulated in the
      visceral adipose tissues of the HOR mice. The expression of peroxisome
      proliferator-activated receptor alpha (PPARalpha) was increased in the HOR mice
      as shown by Western blot analysis. Obesity-resistant animals show enhanced
      peroxisomal beta-oxidation metabolism and reduced fat accumulation in visceral
      adipose tissues by up-regulating the expression of Ech1, peroxisomal or other
      related peroxisomal beta-oxidation marker genes, which may be driven or enhanced
      by the up-regulation of the expression of PPARalpha. However, further validation
      in future studies is required.

PMID- 22977504
TI  - Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with
      breast cancer.
AB  - The overexpression of arachidonyl lipoxygenase-12 (ALOX12) in breast cancer has
      been reported. Hence, we examined whether a non-synonymous polymorphism of ALOX12
      (mRNA, A835G; Gln261Arg) is associated with breast cancer in females. The
      polymorphism was detected in genomic DNA by PCR-RFLP. The association between the
      A835G polymorphism and breast cancer risk was measured by odds ratio (OR) with
      95% confidence intervals (CIs) using Fisher's exact test, and differences were
      considered significant at p<0.05. The frequencies of AA (wild-type), GG
      (homozygous variant) and AG (heterozygous variant) were 59.5, 0.9 and 39.6% in
      the controls, and 39.3, 2.5 and 58.2% in the breast cancer cases, respectively.
      The frequency of the AG genotype was higher in the patients compared to the
      controls (p<0.0014). The frequency of the GG variant was 2.5 and 0.9% in the
      cancer subjects and controls, respectively. The relative risk of breast cancer
      was 2 times greater (OR=2.227) at 95% CI when compared to the relative risk of
      the heterozygous variant. For the GG genotype, the risk was 4 times greater
      (OR=4.125) at 95% CI than that of the controls, suggesting a positive association
      of the AG genotype with the occurrence of breast cancer. The frequencies of the
      polymorphism were different in different populations. The Arg/Gln and Arg/Arg
      variants were associated with an increased risk of breast cancer, and the
      frequencies of the variants differed considerably among various populations. The
      identification of a gene with links to breast cancer may impact screening,
      diagnosis and drug development.

PMID- 22977505
TI  - Association of a polymorphism of BTN2A1 with chronic kidney disease in
      individuals with or without hypertension or diabetes mellitus.
AB  - Hypertension and diabetes mellitus are important risk factors for chronic kidney
      disease (CKD). We previously showed that the C->T polymorphism (rs6929846) of
      BTN2A1 was significantly associated with myocardial infarction. The purpose of
      the present study was to examine an association of rs6929846 of BTN2A1 with CKD
      in individuals with or without hypertension or diabetes mellitus, thereby
      contributing to the personalized prevention of CKD in such individuals
      separately. The study population comprised 7,542 unrelated individuals, including
      2,289 subjects with CKD [estimated glomerular filtration rate (eGFR) <60
      ml/min/1.73 m(2)] and 5,253 controls (eGFR >=60 ml/min/1.73 m(2)) with or without
      hypertension or diabetes mellitus. The Chi-square test, a multivariable logistic
      regression analysis with adjustment for covariates, as well as a stepwise forward
      selection procedure revealed that the C->T polymorphism (rs6929846) of BTN2A1 was
      significantly associated with CKD in normotensive individuals, in diabetic
      individuals and in individuals with hypertension and diabetes mellitus, or
      without either condition, with the T allele representing a risk factor for CKD.
      Stratification of subjects based on hypertension or diabetes mellitus may thus be
      important in order to achieve personalized prevention of CKD with the use of
      genetic information.

PMID- 22977506
TI  - Effects of peripherally administered urocortin 3 on feeding behavior and gastric
      emptying in mice.
AB  - Human and mouse urocortin 3 (Ucn3) were first identified in 2001. Ucn3 binds
      selectively to corticotropin-releasing factor receptor type 2 (CRF-R2). Previous
      studies have shown that centrally administered Ucn3 decreases food intake in
      rats. However, the role of Ucn3 in the regulation of gut motility remains to be
      determined. In the present study, we investigated the effects of peripherally
      administered Ucn3 on food intake and gastric emptying in mice. After
      intraperitoneal (i.p.) administration of Ucn3, food intake was measured in the
      light and dark phases, and the rate of gastric emptying was determined. We found
      that i.p. administration of Ucn3 significantly inhibited feeding behavior in
      mice, and significantly delayed gastric emptying 1-2 h after administration in a
      dose-dependent manner. These results suggest that Ucn3 contributes to the
      modulation of feeding behavior and gut motility. Thus, Ucn3 and CRF-R2 may be
      involved in the pathogenesis of functional gastrointestinal and eating disorders.

PMID- 22977507
TI  - Coding polymorphisms of bone morphogenetic protein 2 contribute to the
      development of childhood IgA nephropathy.
AB  - Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging
      to the transforming growth factor beta (TGFB) superfamily and are important in
      both preservation of kidney function and resistance to injury. BMP2 is highly
      regulated in the kidney, and high affinity binding sites for BMP2 have been
      identified in kidney epithelial cells. BMP2 has been demonstrated to play various
      roles in the pathogenesis of renal diseases. However, the role of the BMP2 gene
      in glomerulonephritis has not been previously investigated. We aimed to evaluate
      the association of BMP2 gene polymorphisms with immunoglobulin A nephropathy
      (IgAN) in children. We evaluated 187 pediatric patients with biopsy-confimed IgAN
      and 262 healthy controls. Two coding single nucleotide polymorphisms (cSNPs) in
      the BMP2 gene [rs235768 (missense, Arg190Ser) and rs1049007 (synonymous,
      Ser87Ser)] were selected and genotyped by direct sequencing. Genotypes of
      rs1049007 were associated with childhood IgAN in the codominant model II (GG vs.
      AA) [p=0.02; OR (95% CI), 0.16 (0.04-0.70)] and in the recessive model [p=0.0023;
      OR (95% CI), 0.16 (0.04-0.69)]. We also found an association between rs235768 and
      IgAN in the codominant model II (TT vs. AA) [p=0.01; OR (95% CI), 0.08 (0.01
      0.57)] and in the recessive model [p=0.0002; OR (95% CI), 0.07 (0.01-0.55)].
      After Bonferroni correction, these associations of rs235768 and rs1049007 with
      IgAN risk remained significant. In the haplotype analysis, the TG haplotype
      [p=0.01; OR (95% CI), 6.76 (1.55-29.50) in the dominant model] and AA haplotype
      [p=0.01; OR (95% CI), 0.08 (0.01-0.59) in the recessive model] showed
      associations with IgAN. The BMP2 gene may contribute to susceptibility to IgAN in
      Korean children.

PMID- 22977508
TI  - Metronomic treatment of temozolomide increases anti-angiogenicity accompanied by
      down-regulated O(6)-methylguanine-DNA methyltransferase expression in endothelial
      cells.
AB  - Metronomic chemotherapy is a continuous low-dose administration of
      chemotherapeutic agents to minimize toxicity and target tumor-associated
      endothelial cells. This therapy is beneficial to anti-angiogenic efficacy which
      is linked to the inhibition of tumor growth. In the present study, we compared
      the anti-angiogenicity of temozolomide in human umbilical vein endothelial cells
      (HUVECs) between conventional and metronomic treatment. Metronomic treatment of
      temozolomide (TMZ) (6.25 and 12.5 MUM) showed increased inhibition of the
      proliferation of HUVECs compared to an equivalent conventional treatment of TMZ.
      The differential effects between conventional and metronomic treatment of TMZ
      were also noted in cell migration and angiogenic tube formation. Notably, the
      expression level of O(6)-methylguanine-DNA methyltransferase (MGMT) was markedly
      reduced in the HUVECs treated with metronomic TMZ (12.5 and 25 MUM) compared to
      cells treated with conventional treatment of TMZ. Accordingly, HUVECs treated
      with metronomic treatment of TMZ were more sensitive to TMZ treatment. Taken
      together, metronomic chemotherapy with TMZ enhances the inhibition of
      angiogenesis accompanied by the down-regulation of MGMT expression in endothelial
      cells when compared to conventional chemotherapy.

PMID- 22977509
TI  - Association of tumor necrosis factor beta genetic polymorphism and sepsis
      susceptibility.
AB  - The association of the tumor necrosis factor beta (TNF-beta) Nco1 genetic
      polymorphism with susceptibility to sepsis was evaluated in 60 consecutive
      patients diagnosed with sepsis and in 148 healthy blood donors. Genomic DNA was
      extracted from peripheral blood cells and a 782 base-pair fragment of the TNF
      beta gene was amplified by PCR. The PCR products were subjected to Nco1
      restriction digestion and analysed by restriction fragment length polymorphism
      analysis. Tumor necrosis factor alpha (TNF-alpha) and the C-reactive protein
      (CRP) serum levels were also determined by ELISA and nephelometry, respectively.
      Among the septic patients, the allelic frequencies of TNFB1 and TNFB2 were 0.2833
      and 0.7166, respectively, and they differed from those observed in the blood
      donors (p=0.0282). The TNFB2 allele frequency was higher in the septic patients
      than in the blood donors [odds ratio=1.65 (CI 95% 1.02-2.69), p=0.0315]. The TNF
      alpha and CRP serum levels and the APACHE II and SOFA clinical scores did not
      differ in the patients with the TNFB1 or TNFB2 alleles (p>0.05). The results
      suggest that the TNFB2 allele is associated with susceptibility to sepsis, but it
      was not found to be associated with the immunological and clinical biomarkers of
      the disease.

PMID- 22977510
TI  - Reduction of matrix metalloproteinase-9 expression by culture filtrate of
      Paecilomyces farinosus J3.
AB  - The aim of the present study was to investigate the anti-tumor effects of a
      culture filtrate of Paecilomyces farinosus J3. Various anti-tumor assays using
      B16 melanoma cells were carried out. Paecilomyces farinosus J3 significantly
      decreased the wound healing capability, invasiveness and angiogenic activity,
      which was confirmed by wound healing, human umbilical vein endothelial cell and
      invasion assays. Paecilomyces farinosus J3 strongly inhibited cell migration,
      tube formation and the angiogenic process in a concentration-dependent manner.
      Zymographic analysis also indicated a reduced expression of matrix
      metalloproteinase-9 (MMP-9), a 92-kDa gelatinase. Taken together, the results
      indicate that the anti-tumor activities of Paecilomyces farinosus J3 originate
      from the reduction of MMP-9 expression in B16F10 cells.

PMID- 22977511
TI  - Low molecular weight heparin suppresses tissue factor-mediated cancer cell
      invasion and migration in vitro.
AB  - Elevated expression of tissue factor (TF) has been associated with an increased
      risk of thrombosis in the majority of cancers. Moreover, treatment of cancer
      patients with low molecular weight heparin (LMWH) appears to have beneficial
      effects that reach beyond controlling the immediate hypercoagulable state. In
      this study, we investigated the influence of the treatment of cancer cells with
      LMWH (0-2,000 MUg/ml) on cell invasiveness and migration in cancer cell lines
      from five separate tissues; pancreatic, breast, colocarcinoma, ovarian and
      melanoma. The rate of cell invasion across collagen IV-coated membranes was
      suppressed in all cell lines tested on incubation with 2,000 MUg/ml LMWH, but
      BxPC-3 and MDA-MB-231 cells also responded to the lowest concentration of 20
      MUg/ml LMWH. Furthermore, the rate of cell migration was reduced to varying
      extents in all of the cell lines tested on incubation with 20 MUg/ml or higher
      concentrations of LMWH. The decrease in the rates of invasion and migration also
      strongly correlated with the reduction in TF protein expression and TF activity
      in these cells following incubation with LMWH. Moreover, the LMWH-mediated
      decreases in cellular invasion in the most affected cell lines (BxPC-3 and MDA-MB
      231) were restored by transfection of the cells with the mammalian pCMV-XL5-TF
      expression vector allowing independent overexpression of TF. In conclusion, LMWH
      appears to suppress the rate of cancer cell invasion and migration in vitro,
      through a mechanism that is at least in part dependent on the TF protein
      expression and activity in cancer cells.

PMID- 22977512
TI  - Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in
      mice.
AB  - Lifestyle-related diseases are associated with overeating and lack of exercise.
      The purpose of this study was to investigate the effect of exercise and high-fat
      diet on plasma adiponectin and nesfatin levels. Mice were housed for 4 weeks in 4
      groups, which included the non-exercise and normal diet (SN), exercise and normal
      diet (EN), non-exercise and high-fat diet (SF) and the exercise and high-fat diet
      (EF) group. The mice in the exercise groups were housed in cages with a running
      wheel and were subjected to voluntary exercise. The food intake (Kcal) of the
      mice in the exercise groups increased compared to that of the mice in the non
      exercise groups (P<0.01). Body weight and visceral fat decreased in the mice in
      the EF group compared to the mice in the SF group (P<0.01 and P<0.05). The
      temperature of the mice in the EF group increased compared to that of the mice in
      the SN group (P<0.05). Blood glucose, insulin (P<0.01), cholesterol (P<0.01) and
      triglyceride concentrations (P<0.01) increased in the SF group compared to the
      normal diet groups. Furthermore, plasma insulin and cholesterol concentrations
      increased in the SF group compared to the exercise groups (P<0.01). Plasma
      adiponectin and nesfatin-1 levels in the SF group decreased compared to the SN
      group (P<0.05). Exercise under a high-fat diet antagonized the significant
      decrease in the nesfatin-1 level. Exercise together with a high-fat diet affected
      the plasma levels of adiponectin and nesfatin. It is therefore suggested that
      exercise together with a high-fat diet can affect various diseases via
      adiponectin and nesfatin.

PMID- 22977513
TI  - 'Malignant melanoma microecosystem': Immunohistopathological insights into the
      stromal cell phenotype.
AB  - Cutaneous malignant melanoma (MM) is rooted in the dermal connective tissue,
      which consists of apparently unremarkable stromal cells as they appear upon
      regular histopathological examination. However, a number of in vitro studies have
      shown that these cells produce diverse types of cytokines, growth factors and
      enzymes in excess. In addition, they store and probably release various
      structural components of the extracellular matrix (ECM). Most of the current
      information comes from in vitro experiments, and these findings do not always
      correlate with investigations carried out using excised human MM tissue. The MM
      stroma connection appears crucial to the regulation of neoplastic growth,
      invasiveness and initial metastatic spread. However, little is known about the in
      vivo intracellular storage and extracellular deposits of specific ECM
      macromolecules located inside and around MM lesions. This review summarizes
      various distinct features of the peri-MM stroma, which shows an intracytoplasmic
      abundance of Factor XIIIa, versican and various alpha (IV) collagen chains. The
      area exhibiting such changes corresponds to the location where neoangiogenesis
      commonly develops and where extravascular unicellular metastatic MM lesions are
      possibly found. Some of these inconspicuous migratory malignant melanocytes may
      actually correspond to MM stem cells. Their presence was found to be
      significantly associated with an increased risk for distant metastases,
      particularly in the sentinel lymph nodes. Although much remains to be learned,
      active intervention of the ECM appears likely in the inconspicuous early dermal
      metastatic migration of MM cells.

PMID- 22977515
TI  - Trifluorothymidine exhibits potent antitumor activity via the induction of DNA
      double-strand breaks.
AB  - TAS-102 is an oral anticancer drug composed of trifluorothymidine (TFT) and TPI
      (an inhibitor of thymidine phosphorylase that strongly inhibits the
      biodegradation of TFT). Similar to 5-fluorouracil (5FU) and 5-fluoro-2'
      deoxyuridine (FdUrd), TFT also inhibits thymidylate synthase (TS), a rate
      limiting enzyme of DNA biosynthesis, and is incorporated into DNA. TFT exhibits
      an anticancer effect on colorectal cancer cells that have acquired 5FU and/or
      FdUrd resistance as a result of the overexpression of TS. Therefore, we examined
      the mode of action of TFT-induced DNA damage after its incorporation into DNA.
      When HeLa cells were treated with TFT, the number of ring-open aldehyde forms at
      apurinic/apyrimidinic sites increased in a dose-dependent manner, although we
      previously reported that no detectable excisions of TFT paired to adenine were
      observed using uracil DNA glycosylases, thymine DNA glycosylase or methyl-CpG
      binding domain 4 and HeLa whole cell extracts. To investigate the functional
      mechanism of TFT-induced DNA damage, we measured the phosphorylation of ATR, ATM,
      BRCA2, chk1 and chk2 in nuclear extracts of HeLa cells after 0, 24, 48 or 72 h of
      exposure to an IC(50) concentration of TFT, FdUrd or 5FU using Western blot
      analysis or an enzyme-linked immunosorbent assay (ELISA). Unlike FdUrd and 5FU,
      TFT resulted in an earlier phosphorylation of ATR and chk1 proteins after only 24
      h of exposure, while phosphorylated ATM, BRCA2 and chk2 proteins were detected
      after more than 48 h of exposure to TFT. These results suggest that TFT causes
      single-strand breaks followed by double-strand breaks in the DNA of TFT-treated
      cells. TFT (as TAS-102) showed a more potent antitumor activity than oral 5FU on
      CO-3 colon cancer xenografts in mice, and such antitumor potency was supported by
      the increased number of double-strand breaks occurring after single-strand breaks
      in the DNA of the TFT-treated tumors. These results suggest that TFT causes
      single-strand breaks after its incorporation into DNA followed by double-strand
      breaks, resulting in DNA damage. This effect of TFT on DNA may explain its potent
      anticancer activity in cancer therapy.

PMID- 22977514
TI  - Detection of circulating tumor cells: Clinical relevance of a novel metastatic
      tumor marker.
AB  - Most cancer-related deaths are caused by the hematogenous spread of cancer cells
      to distant organs and their subsequent metastasis. During the early stages of the
      metastatic cascade, cancer cells disseminate from the primary site via the
      lymphatic vessels and/or by hematogenous routes. Circulating tumor cells (CTCs),
      cancer cells that have disseminated into the systemic circulation, may be a
      predictor of poor prognosis in several carcinomas. An understanding of the
      molecular mechanisms involved in the blood-borne dissemination of cancer cells
      may help to clarify the process of metastasis and provide a powerful and non
      invasive approach for anticancer treatments that are tailored to individual
      patients.

PMID- 22977517
TI  - Activin A maintains pluripotency markers and proliferative potential of human
      induced pluripotent stem cells.
AB  - To investigate the role of Activin A in the embryoid bodies (EBs) of human
      induced pluripotent stem (iPS) cells, EBs were transferred onto dishes coated
      with Matrigel after 4 days of incubation with Activin A and observed under a
      microscope. Alkaline phosphatase staining and immunostaining were performed to
      analyze the pluripotency of the cells, and the MTS assay was performed to analyze
      their proliferative potential. Fourteen days after EB formation, cells cultured
      with Activin A (100 ng/ml) showed no morphological alterations. Cells cultured
      with 10-100 ng/ml of Activin A were positive for alkaline phosphatase staining,
      while cells cultured with 0-3 ng/ml showed negative staining. Cells cultured with
      10 ng/ml of Activin A were positive for Oct3/4, Nanog, SSEA-4 and TRA-1-60, while
      cells cultured with 0 ng/ml Activin A were negative. Cells cultured with 3-30
      ng/ml of Activin A maintained their proliferative potential, while loss of
      proliferative potential was observed in cells cultured with 100 ng/ml Activin A.
      In conclusion, Activin A maintained pluripotency markers in human iPS cells
      cultured as EBs with Activin A.

PMID- 22977518
TI  - Feasibility of large-scale screening using N-ERC/mesothelin levels in the blood
      for the early diagnosis of malignant mesothelioma.
AB  - A large-scale screening involving the measurement of N-ERC/mesothelin levels in
      blood using an ELISA system for the early diagnosis of malignant mesothelioma
      (MM) was carried out in individuals with a history of employment at construction
      sites. Approximately 30,000 subjects were screened. Of the 80 subjects with high
      risk values, one male patient was diagnosed as having MM based on a PET study and
      histopathology. This is the first report of the pre-clinical diagnosis of MM
      based on blood test screening. In addition, plasma levels of N-ERC/mesothelin may
      be effectively used for monitoring relapse after surgery.

PMID- 22977516
TI  - Use of protein array technology to investigate receptor tyrosine kinases
      activated in hepatocellular carcinoma.
AB  - Receptor tyrosine kinases (RTKs) play a role in various processes, including cell
      growth, differentiation, apoptosis and carcinogenesis. RTKs are activated in
      various types of cancers, including breast, stomach, colon, pancreas and liver
      cancer and hepatocellular carcinoma (HCC). In the present study, protein array
      technology was used to analyze the expression status of various RTKs activated in
      HCC. The expression of activated RTKs was examined in the HCC cell lines, Alex,
      HuH7, Li-7, Hep3B, HLE and HLF; in the human normal hepatocyte cell line, hNHeps;
      and in human HCC and adjacent non-cancerous tissues. Of the 42 different phospho
      RTKs, 15 (ErbB2, ErbB3, ErbB4, FGFR2alpha, FGFR3, insulin R, Mer, PDGFRbeta, c
      Ret, ROR2, Tie, TrkA, VEGFR3, EphA1 and EphA4) were activated in some of the
      cancer cell lines studied. Among these, only ErbB2 was activated in all the HCC
      cell lines examined. Also, in vitro experiments were performed in subcutaneous
      HCC-bearing athymic nude mice to determine the therapeutic effects of inhibiting
      ErbB2 activation using the ErbB2-targeting drug trastuzumab. The results revealed
      that trastuzumab markedly suppressed the growth of HCC. These data suggest that
      ErbB2 is activated in HCC and that trastuzumab may play a role in the treatment
      of this disease. In addition, the use of protein array technology is proposed as
      a tool for detecting the expression of activated RTKs and identifying an
      effective RTK-based therapy.

PMID- 22977519
TI  - Rosiglitazone and retinoic acid inhibit proliferation and induce apoptosis in the
      HCT-15 human colorectal cancer cell line.
AB  - The aim of this study was to explore the effects of rosiglitazone (RSG) in
      combination with all-trans retinoic acid (ATRA) on the proliferation and
      apoptosis of the HCT-15 human colorectal cancer cell line. HCT-15 cells were
      divided into a blank control group, a vehicle control group and experimental
      groups (RSG only or ATRA only or RSG plus ATRA). Growth inhibition was examined
      using the MTT assay. Apoptosis and cell cycle progression were examined by flow
      cytometry. The expression of COX-2, MMP-7 and TIMP-1 was examined by
      immunocytochemistry. RSG alone inhibited HCT-15 cell proliferation in a
      concentration- and time-dependent manner (P<0.05). The combination of RSG and
      ATRA exhibited significant synergy (q>1.15). RSG or ATRA alone effectively
      increased the proportion of cells in the G0/G1 phase and decreased the proportion
      of cells in the S phase, thus inducing apoptosis (P<0.05). The combination of RSG
      and ATRA resulted in even stronger G1 cell cycle arrest (P<0.05). HCT-15 cells
      expressed COX-2, MMP-7 and TIMP-1, with positive expression rates in the control
      group of 66.79, 73.21 and 64.08%, respectively. After the combined application of
      RSG and ATRA, the positive rates significantly declined to only 19.33, 20.58 and
      13.13%, respectively (P<0.01). In conclusion, the combination of RSG and ATRA
      reduced the expression of COX-2, MMP-7 and TIMP-1, caused cell cycle arrest at
      the G1 phase and induced apoptosis, which resulted in the inhibition of cell
      proliferation in the HCT-15 human colorectal cancer cell line.

PMID- 22977520
TI  - Vitamin B6 regulates mRNA expression of peroxisome proliferator-activated
      receptor-gamma target genes.
AB  - We previously demonstrated that vitamin B6 suppresses tumorigenesis in the colon
      of mice and exerts an anti-inflammatory effect through the inhibition of NF
      kappaB activation. As these effects resemble the pharmacological properties of
      thiazolidinedione (TZD), a synthetic peroxisome proliferator-activated receptor
      gamma (PPARgamma) ligand, this study was designed to examine the effect of
      vitamin B6 on the activation of PPARgamma and adipogenesis in 3T3-L1 adipocyte
      cells. Pyridoxal 5'-phosphate (PLP), one of the vitamin B6 derivatives, was shown
      to promote adipogenesis in the 3T3-L1 adipocytes. In addition, PLP specifically
      induced mRNA expression of PPARgamma target genes in the 3T3-L1 adipocytes and
      enhanced the lipid accumulation and adipocyte fatty acid-binding protein (aP2)
      mRNA expression in NIH3T3 cells stably expressing PPARgamma. Furthermore, the
      administration of vitamin B6 increased the expression of aP2 mRNA in mouse
      adipose tissues. Collectively, these observations suggest a novel function of
      vitamin B6 as an activator for PPARgamma, which may contribute to the anti-tumor
      and anti-inflammatory effects of vitamin B6.

PMID- 22977521
TI  - High TSC22D3 and low GBP1 expression in the liver is a risk factor for early
      recurrence of hepatocellular carcinoma.
AB  - Recurrence after liver resection for hepatocellular carcinoma (HCC) is a major
      clinical problem, and prognostic markers for recurrence are urgently required.
      For 390 HCC cases, segmented linear regression analysis with two segments was
      performed, and the interval for the early and late recurrence groups was
      partitioned at the crosspoint (676 days). We investigated whether gene expression
      in non-tumorous tissues of remnant liver from 39 hepatitis C virus-positive HCC
      cases may be associated with early recurrence of this disease. By microarray
      analysis, 21 genes were identified as candidate recurrence-associated genes.
      Further gene expression analysis was performed, and the localization and
      expression of the gene products of these candidate genes were
      immunohistochemically evaluated. Low expression of the GBP1 gene and high
      expression of the TSC22D3 gene were significantly (both P=0.04) associated with
      the risk of early recurrence. Through backward step-wise multivariate logistic
      regression analysis for the 21 candidate genes, high expression of GBP1 reduced
      [odds ratio (OR)=0.20; 95% confidence interval (CI) 0.06-0.73, P=0.02] and high
      expression of TSC22D3 increased the risk of early recurrence (OR=19.6; 95% CI
      1.14-337.2; P=0.04). Immunohistochemical analysis revealed that hepatocytes
      showed strong membranous expression for GBP1 in the late recurrence group, but
      weak membranous expression for GBP1 in the early recurrence group. TSC22D3 was
      frequently expressed in lymphocytes and in a few hepatocytes in tissues of the
      early recurrence group. Our observations suggest that the combination of the high
      expression of the TSC22D3 gene and low expression of the GBP1 gene in the non
      tumorous tissue of the remnant liver is significantly associated with early
      recurrence after surgical resection of HCC.

PMID- 22977522
TI  - Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced
      hepatocellular carcinoma: A comparative study.
AB  - Sorafenib is a kinase-targeted drug that has high efficacy for advanced
      hepatocellular carcinoma (HCC). The aim of the present study was to determine
      whether sorafenib is more effective than hepatic arterial infusion chemotherapy
      (HAIC) for HCC. Twenty patients treated with sorafenib (sorafenib group)
      initiated at 800 mg/day and 45 patients treated with HAIC (HAIC group) for
      unresectable Child-Pugh A advanced HCC were investigated retrospectively. The
      treatment effect was assessed using the Response Evaluation Criteria in Solid
      Tumors (RECIST). As a result, the overall response rate was significantly lower
      in the sorafenib group than in the HAIC group (P=0.03), while the disease control
      and survival rates did not differ between the two groups. In the sorafenib group,
      treatment was discontinued in 19 patients, including 12 due to side effects. In
      subgroups of patients treated with sorafenib, the survival rate was significantly
      lower in patients (n=11) administered sorafenib for <60 days compared to those
      (n=9) treated for >=60 days. A shorter treatment period (<60 days) was an
      independent risk factor for unfavorable survival [hazard ratio (HR), 3.34; 95%
      confidence interval (CI), 1.45-7.66 vs. HAIC], while survival in patients treated
      with sorafenib for >=60 days did not differ from those treated with HAIC (HR,
      0.79; 95% CI, 0.27-2.34). In conclusion, the disease control and survival rates
      of patients treated with sorafenib for advanced HCC were comparable to such rates
      in patients treated with HAIC. However, the prognosis was poor when long-term
      sorafenib treatment was not possible due to side effects, demonstrating the
      importance of patient selection for sorafenib treatment.

PMID- 22977523
TI  - Functional interaction of BRCA1/ATM-associated BAAT1 with the DNA-PK catalytic
      subunit.
AB  - Ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK)
      play a crucial role in the initial stages of cell response, when cells are
      exposed to DNA insult such as ionizing radiation (IR) and chemical agents. We
      previously demonstrated that ATM requires BAAT1 for its activation in response to
      IR. In the present study, BAAT1 was found to bind to the DNA-PK catalytic subunit
      (DNA-PKcs) and SMC1. Biochemical analysis indicated that several regions of BAAT1
      were responsible for the interaction with these proteins, and their binding
      affinity was altered after treatment with the IR mimetic, neocarzinostatin (NCS).
      Phosphorylation of the DNA-PKcs at Ser2056 and SMC1 at Ser966 was induced by NCS,
      while phosphorylation was reduced when BAAT1 was depleted by siRNA. These results
      indicate that BAAT1 globally regulates DNA damage signaling during the early
      stages of apoptosis.

PMID- 22977524
TI  - Addition of erlotinib to fluoropyrimidine-oxaliplatin-based chemotherapy with or
      without bevacizumab: Two sequential phase I trials.
AB  - The combination of EGFR inhibitors and anti-angiogenic drugs has a strong pre
      clinical rationale, yet its use has produced controversial clinical results. We
      conducted two sequential phase I trials to evaluate the feasibility and the
      recommended dose of erlotinib when combined with fluoropyrimidine-oxaliplatin
      based chemotherapy with or without bevacizumab. A total of 21 metastatic
      colorectal cancer (mCRC) patients were treated in two sequential phase I trials.
      In the first trial, 12 patients were treated with escalating doses of erlotinib
      plus FOLFOX. In the second, 9 patients were treated with escalating doses of
      erlotinib combined with oxaliplatin, capecitabine and bevacizumab. No MTD was
      reached in either of the trials. The only dose-limiting toxicities observed were
      neutropenia and diarrhea. No unexpected toxicities were noted. Hematological
      toxicity was the most frequently noted adverse event with infusional 5FU therapy,
      while gastrointestinal toxicity was the most common adverse event. In the second
      trial most patients withdrew from treatment due to toxicity, and less than half
      completed the therapeutic program as per protocol, mostly due to toxicity. In
      conclusion, the present study confirms the disappointing results of the double
      combination of EGFR inhibitors and anti-angiogenic drugs in mCRC patients.

PMID- 22977525
TI  - Tyrosine phosphatase PTPRD suppresses colon cancer cell migration in coordination
      with CD44.
AB  - PTPRD is a receptor-type tyrosine-protein phosphatase. Recent analyses of
      comprehensive mutations and copy numbers have revealed that PTPRD is frequently
      mutated and homozygously deleted in various types of cancer, including
      glioblastoma, melanoma, breast and colon cancer. However, the molecular functions
      of PTPRD in cancer progression have yet to be elucidated. Herein, PTPRD
      suppressed colon cancer cell migration and was required for appropriate cell-cell
      adhesion. In addition, PTPRD regulated cell migration in cooperation with beta
      catenin/TCF signaling and its target CD44. Furthermore, expression levels of
      PTPRD were down-regulated in highly invasive cancers and were significantly
      correlated with patient survival. Our findings suggest that PTPRD is required for
      colon cancer invasion and progression.

PMID- 22977526
TI  - Cancer stem cell-related factors are associated with the efficacy of pre
      operative chemoradiotherapy for locally advanced rectal cancer.
AB  - Pre-operative chemoradiotherapy (CRT) is an important neoadjuvant therapy for
      locally advanced rectal cancer. In the present study, we investigated the factors
      that influence the efficacy of pre-operative CRT in locally advanced rectal
      cancer. We divided 50 patients with locally advanced rectal carcinoma treated
      with pre-operative CRT into two groups according to the grade of tumor response
      to pre-operative CRT: low-sensitivity group and high-sensitivity group. As
      candidates for the prediction of sensitivity to pre-operative CRT,
      clinicopathological factors and 12 biomarkers, including factors related to tumor
      growth, cell cycle, apoptosis, tumor stroma and cancer stem cells, were examined
      immunohistochemically in 48 resected specimens. Thirty-one tumors showed high
      sensitivity and 19 showed low sensitivity to pre-operative CRT. The status of
      stem cell-related factors, CD133 and CD24, was significantly associated
      respectively with sensitivity to pre-operative CRT (P=0.003, P=0.029). In 10
      tumors positive for both CD133 and CD24, low sensitivity to CRT was found in 9
      (90%), whereas in 16 tumors negative for both CD133 and CD24, low sensitivity was
      found in 3 (19%). Other pathological parameters were not associated with tumor
      response to pre-operative CRT. In conclusion, overexpression of cancer stem cell
      related factors, CD133 and CD24, is associated with the sensitivity of locally
      advanced rectal cancer to pre-operative CRT.

PMID- 22977527
TI  - Nuclear expression of N-myc downstream regulated gene 1/Ca(2+)-associated protein
      43 is closely correlated with tumor angiogenesis and poor survival in patients
      with gastric cancer.
AB  - Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca(2+)-associated protein
      43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis
      depending on tumor type. In this study, we examined whether NDRG1/Cap43 is a
      marker of good or poor prognosis in gastric cancer patients, and whether it is
      associated with tumor stromal responses, including angiogenesis and macrophage
      infiltration. The expression levels of NDRG1/Cap43, the number of CD68-positive
      macrophages and the CD34-positive microvessel density were analyzed by
      immunohistochemistry in 129 gastric cancer patients, including 65 with the
      intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in
      the nucleus and the membrane was evaluated. Nuclear NDRG1/Cap43 expression was
      found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%)
      patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression
      was significantly associated with pathological stage in the intestinal type
      (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression
      was also closely associated with infiltrating macrophages (P=0.001) and tumor
      angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43
      expression was associated with poor prognosis in both the intestinal (P=0.001)
      and the diffuse types of gastric cancer (P=0.047). By contrast, membranous
      NDRG1/Cap43 expression was not associated with the overall survival of gastric
      cancer patients with either the intestinal or diffuse type of gastric cancer. The
      expression of NDRG1/Cap43 in the nucleus may be a predictive biomarker for
      malignant progression in the intestinal type of gastric cancer, preferable to the
      expression of NDRG1/Cap43 in the membrane.

PMID- 22977528
TI  - Arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells through
      activation of caspase-3 and inhibition of HERG channels.
AB  - Arsenic trioxide (As(2)O(3)) has been widely used to treat patients with acute
      promyelocytic leukemia and has also been shown to exhibit therapeutic effects on
      various types of solid tumors, including gastric cancer and lung carcinoma.
      Breast cancer is a type of solid tumor whose incidence has been increasing for
      many years. The present study was designed to investigate the effects of
      As(2)O(3) on the human breast cancer cell line MCF-7, and to explore its
      potential mechanisms. The MTT assay demonstrated that As(2)O(3) decreased the
      cellular viability of MCF-7 cells in a concentration-dependent manner.
      Morphological observation, the TUNEL assay and flow cytometric analysis revealed
      that apoptosis was involved in the process. An assay for caspase-3 activity
      suggested that the apoptosis was mediated through caspase-3 activation. Further
      investigation indicated that protein levels of the human ether-a-go-go-related
      gene (HERG) were markedly downregulated by As(2)O(3). Taken together, the results
      indicate that arsenic trioxide induces the apoptosis of human breast cancer MCF-7
      cells at least in part through the activation of caspase-3 and the decrease in
      HERG expression.

PMID- 22977529
TI  - Expression profile of HMBOX1, a novel transcription factor, in human cancers
      using highly specific monoclonal antibodies.
AB  - Homeobox containing 1 (HMBOX1) is a novel transcription factor. However, the
      expression of HMBOX1 and its functions in human cancer tissues and cell lines
      have not been fully defined. We generated two specific monoclonal antibodies,
      2A5F4 and 4A4F2, against human HMBOX1. In the present study, these two anti
      HMBOX1 antibodies were used to investigate the protein expression profile of
      HMBOX1 in various human cancer tissues and cell lines. The results showed that
      HMBOX1 in kidney tissue was mainly expressed in the renal tubule; the expression
      level of HMBOX1 was much higher in clear-cell carcinoma of the kidney originating
      from the renal tubule. Additionally, high levels of HMBOX1 protein were detected
      not only in pancreatic cancer tissue but also in the adjacent normal tissue.
      Notably, the expression level of HMBOX1 in liver cancer was dramatically
      decreased compared with that in the adjacent normal tissue. Abnormal expression
      of HMBOX1 in different types of carcinoma tissues suggests that HMBOX1 may be
      involved in the pathobiology of tumors.

PMID- 22977530
TI  - Retinoid acid receptors in human colorectal cancer: An unexpected link with
      patient outcome.
AB  - The status of the three retinoic acid receptors (RARs) alpha, beta and gamma in
      human colorectal cancer (CRC) has not as yet been examined. RARs are in part
      responsible for the actions of the retinoids (vitamin A and its derivatives),
      which are essential for human health and survival due to their extensive
      involvement in numerous cellular processes, in particular in epithelial
      morphology. The present study examined the expression of the three RARs in CRC
      using immunohistochemical analysis of paraffin-embedded tissue sections. RAR
      expression in tumor (T) and adjacent non-tumor (NT) specimens from stage I (n=6),
      stage II (n=34), stage III (n=26) and stage IV (n=14) CRC patients was compared
      with that in normal mucous membranes (n=10) from control individuals. The
      findings were correlated with tumor grade, treatment response (progression during
      treatment, remission, chemoresistance) and survival as clinicopathological
      parameters. RARalpha and gamma expression was decreased with CRC stage in the T
      tissues (P=0.016 and P=0.052, respectively), suggesting that they may be used as
      predictive markers. RARbeta expression in the NT tissues was associated with a
      more favorable prognosis (P=0.04). These results provide important information on
      the tumor microenvironment (the area adjacent to tumor cells).

PMID- 22977531
TI  - Evaluation of the combined expression of chemokine SDF-1alpha and its receptor
      CXCR4 as a prognostic marker for gastric cancer.
AB  - Chemokine stromal cell-derived factor (SDF)-1alpha and its receptor CXC chemokine
      receptor 4 (CXCR4) have been shown to impact cancer progression. Accumulating
      evidence suggests that CXCR4 and SDF-1alpha expression is useful for evaluating
      the risk of gastric cancer progression. Thus, combined analysis of SDF-1alpha and
      CXCR4 should have high prognostic potential as a molecular marker for gastric
      cancer. We investigated the expression of SDF-1alpha and CXCR4 using
      immunohistochemistry in relation to prognosis, clinicopathological features and
      clinical outcomes in 221 cases of primary gastric cancer. Patients were
      categorized into three groups according to CXCR4 and SDF-1alpha expression: high
      CXCR4/high SDF-1alpha, low CXCR4/low SDF-1alpha, and high CXCR4/low SDF-1alpha -
      low CXCR4/high SDF-1alpha. No significant differences were noted in age, gender,
      histology, tumor location, lymphovascular invasion or proportion of tumor size >5
      cm among the three groups. However, high CXCR4/high SDF-1alpha expression in
      tumor cells was significantly associated with depth of invasion of the tumor,
      lymph node involvement, and higher tumor stage compared to tumors with low
      CXCR4/low SDF-1alpha expression or high CXCR4/low SDF-1alpha - low CXCR4/high SDF
      1alpha expression. Furthermore, patients with high CXCR4/high SDF-1alpha
      expression had the worst patient prognosis, whereas patients who had low
      CXCR4/low SDF-1alpha expression showed the most favorable prognosis. In
      conclusion, CXCR4 and SDF-1alpha are useful prognostic factors in gastric cancer,
      and the combination of high CXCR4 protein expression with high SDF-1alpha
      expression suggests a dismal prognosis.

PMID- 22977532
TI  - Overexpression of engulfment and cell motility 1 promotes cell invasion and
      migration of hepatocellular carcinoma.
AB  - Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype
      of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in
      hepato-cellular carcinoma (HCC), but the molecular mechanisms of their
      therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue
      samples from 131 cases and in 5 HCC cell lines was determined by
      immunohistochemistry, quantitative RT-PCR and Western blotting. To functionally
      characterize Elmo1 in HCC, Elmo1 expression in the HCCLM3 cell line was blocked
      by siRNA. Cell migration was measured by wound healing and transwell migration
      assays in vitro. Elmo1 overexpression was significantly correlated with cell
      invasion and the poor prognosis of HCC. Elmo1-siRNA-treated HCCLM3 cells
      demonstrated a reduction in cell migration. The present study demonstrated for
      the first time that the suppression of Elmo1 expression inhibits cell invasion in
      HCC.

PMID- 22977533
TI  - Effect of high hydrostatic pressure on the expression of glutamine synthetase in
      rat retinal Muller cells cultured in vitro.
AB  - The aim of the present study was to examine the expression of glutamine
      synthetase (GS) in rat retinal Muller cells induced by different levels of
      hydrostatic pressure using a novel pressure mechanism. pH, PCO(2) or PO2 in
      culture medium as determined by gas analysis was used to examine the pressure
      mechanism. GS expression in the Muller cells at different levels of hydrostatic
      pressure (0, 20, 40, 60 and 80 mmHg/24 h) was examined using immunofluorescence,
      real-time PCR and Western blotting. There was no significant difference in pH,
      PCO(2) or PO(2) in the culture medium by gas analysis at the different
      hydrostatic pressure levels (p>0.05). Immunofluorescence staining showed that GS
      was expressed in the Muller cells. The expression of GS in the 40 mmHg/24 h and
      the 60 mmHg/24 h groups was increased significantly compared to that in the 0
      mmHg/24 h group (p<0.05). These results suggest that the pressure mechanism which
      was constructed was effective and that moderate pressure promotes the up
      regulation of GS in active Muller cells.

PMID- 22977534
TI  - Significance of CXCR4, phosphorylated STAT3 and VEGF-A expression in resected non
      small cell lung cancer.
AB  - C-X-C chemokine receptor type 4 (CXCR4) plays an important role in determining
      the metastatic potential of non-small cell lung cancer. In order to elucidate the
      effect and mechanism of CXCR4 in tumor angiogenesis we evaluated the clinical
      significance of CXCR4, phosphorylated signal transducer and activator of
      transcription 3 (P-STAT3), and vascular endothelial growth factor (VEGF)
      expression in patients with completely resected non-small cell lung cancer
      (NSCLC). A total of 208 cases of resected NSCLC were collected, and expression of
      CXCR4, P-STAT3 and VEGF-A in tumor tissue was investigated using
      immunohistochemistry (IHC). We reviewed the patient clinical records to determine
      the association of the expression of these proteins with the clinical course of
      the disease. Expression of CXCR4, P-STAT3 and VEGF-A was detected in 56.3, 46.2
      and 51.9% of the samples, respectively. We observed co-expression between CXCR4,
      P-STAT3 and VEGF-A. Using multivariate analysis, the expression levels of CXCR4
      and VEGF-A were identified as independent prognostic factors that affected
      overall survival. In conclusion, the results of this study suggest that CXCR4, P
      STAT3 and VEGF-A expression may play a role in tumor progression and angiogenesis
      of NSCLC. However, further studies are needed to uncover the detailed mechanism
      that underlies the role of these proteins in NSCLC.

PMID- 22977535
TI  - Imaging agents for in vivo molecular profiling of disseminated prostate cancer:
      Cellular processing of [(111)In]-labeled CHX-A"DTPA-trastuzumab and anti-HER2 ABY
      025 Affibody in prostate cancer cell lines.
AB  - The treatment of disseminated prostate cancer remains a great challenge in
      current oncology practice. The proliferation of prostate cancer cells is
      testosterone-driven, but clonal selection during androgen deprivation therapy
      promotes the development of androgen-independent (hormone-refractory) cells,
      which become phenotypically dominant. Human epidermal growth factor receptor type
      2 (HER2) is capable of activating the androgen receptor pathway, even in the
      absence of the ligand. The detection of phenotypic changes associated with the
      development of androgen independence may influence patient management, suggesting
      the initiation of a second-line therapy. This study aimed to establish the level
      of HER2 expression in a number of prostate cancer cell lines (LNCaP, PC3 and
      DU145) in order that they be used as models in further studies, and to evaluate
      the binding and cellular processing of [(111)In]-labeled trastuzumab and the anti
      HER2 synthetic Affibody molecule ABY-025 in these cell lines. The expression of
      HER2 was demonstrated and quantified in all three tested prostate cancer cell
      lines. Studies on cellular processing demonstrated that internalization of both
      conjugates increased continuously during the whole incubation. The
      internalization rate was approximately equal for both monoclonal antibodies and
      Affibody molecules. In both cases, internalization was moderately rapid. Such
      features would definitely favor the use of radiometal labels for trastuzumab and,
      most likely, for affibody molecules. The level of HER2 expression in these cell
      lines is sufficient for in vivo molecular imaging.

PMID- 22977536
TI  - Thalidomide and irradiation combination therapy increases substance P levels in
      vitro.
AB  - Thalidomide is an anti-angiogenic agent that is used in the treatment of cancer.
      However, in many cases, particularly in patients with breast cancer, thalidomide
      treatment alone is insufficient and must be combined with other drugs or
      therapies. In the clinical setting, thalidomide is most commonly used in
      combination with radiation therapy. However, the exact mechanisms of its effect
      are unkown. Radiotherapy alters the expression of substance P, which is
      considered a crucial pro-angiogenic peptide. To determine whether thalidomide and
      radiotherapy in combination overcome the limitations of each as monotherapy, we
      examined the effects of the combination on the growth of breast cancer cells as
      well as on the expression of substance P in vitro. Mouse breast cancer cells
      (4T1) and cells produced from metastatic lesions (4THMpc) were treated with
      radiotherapy (RT) (45 Gy) alone, thalidomide (Thal) (40 MUg/ml) alone or
      combination therapy (40 MUg/ml Thal + 45 Gy RT), and compared with control cells.
      MTS, Live/Dead and trypan blue exclusion assays were used to evaluate the
      cytotoxic effects of the treatments. The levels of substance P in the conditioned
      media and in the cell lysates were determined by a substance P ELISA kit, and
      changes in the protein content were analyzed by Western blotting. Thalidomide
      alone resulted in a significant inhibition in the growth of the 4T1 (34.1%) and
      4THMpc (52.6%) cell lines. RT alone inhibited the growth of the 4T1 (19.2%) and
      4THMpc (23.31%) cell lines. The combination therapy enhanced the growth
      inhibition noted in the 4T1 (47.9%) and 4THMpc (62.03%) cell lines. The
      expression of substance P in the conditioned media and in the cell lysates
      increased within 72 h of RT. This increase was significantly enhanced with the
      combination therapy. These data indicate that thalidomide inhibits breast cancer
      cell growth and potentiates the anti-tumor effects of radiation at appropriate
      doses.

PMID- 22977537
TI  - Analysis of estrogen receptor isoforms and variants in breast cancer cell lines.
AB  - In the present study, the expression of estrogen receptor (ER)alpha and ERbeta
      isoforms in ER-positive (MCF7, T-47D and ZR-75-1) and ER-negative (MDA-MB-231, SK
      BR-3, MDA-MB-453 and HCC1954) breast cancer cell lines was investigated. ERalpha
      mRNA was expressed in ER-positive and some ER-negative cell lines. ERalpha
      Delta3, Delta5 and Delta7 spliced variants were present in MCF7 and T-47D cells;
      ERalpha Delta5 and Delta7 spliced variants were detected in ZR-75-1 cells. MDA-MB
      231 and HCC1954 cells expressed ERalpha Delta5 and Delta7 spliced variants. The
      ERbeta1 variant was expressed in all of the cell lines and the ERbeta2 variant in
      all of the ER-positive and some ER-negative cell lines (MDA-MB-231, MDA-MB-453
      and SK-BR-3). MCF7, ZR-75-1, MDA-MB-453, HCC1954 and T-47D cells expressed
      ERbeta5. All cell lines expressed an ERalpha 66-kDa protein band, and some
      expressed the truncated 42-kDa variant. ERbeta1 was detected in all of the cell
      lines in addition to a 38-44 kDa variant. The results indicate that breast cancer
      cell lines widely used in research and reported as being ER-negative express
      ERalpha and/or ERbeta mRNA and protein.

PMID- 22977538
TI  - Anti-inflammatory effect of patchouli alcohol isolated from Pogostemonis Herba in
      LPS-stimulated RAW264.7 macrophages.
AB  - Pogostemonis Herba has long been used in traditional Chinese medicine for the
      treatment of inflammation-related disorders. Patchouli alcohol (PA) isolated from
      Pogostemonis Herba is a tricyclic sesquiterpene that is known to exert a variety
      of pharmacological activities. The present study aimed to investigate the anti
      inflammatory effect of PA on lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
      Pre-treatment with PA at concentrations of 10, 20 or 40 MUM dose-dependently
      decreased the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-6, nitric oxide (NO) and prostaglandin E(2) in LPS-stimulated RAW264.7
      cells. In addition, PA treatment also reversed the increased mRNA expression of
      TNF-alpha, IL-1beta, IL-6, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase (COX)-2 caused by LPS in RAW264.7 cells. These results indicate
      that PA is an important anti-inflammatory constituent of Pogostemonis Herba and
      that its anti-inflammatory effect may be mediated, at least in part, by down
      regulation of the mRNA expression of a panel of inflammatory mediators, such as
      TNF-alpha, IL-1beta, IL-6, iNOS and COX-2.

PMID- 22977539
TI  - A primary experience of conventional fractionated three-dimensional conformal
      partial breast irradiation for early-stage breast cancer.
AB  - Recently, a number of clinical trials assessing partial breast irradiation (PBI),
      in particular accelerated partial breast irradiation, have been conducted in
      patients with early-stage breast cancer after breast-conserving surgery (BCS) in
      Europe and the US. By contrast, PBI is rarely performed in Eastern countries. In
      general, there are many physiological differences between Eastern and Western
      populations, and whether PBI is suitable for Eastern populations remains
      uncertain. Moreover, PBI is still in the stage of clinical research, and numerous
      questions have yet to be resolved. Thus, we designed a PBI trial to explore its
      feasibility and effectiveness for Eastern patients. According to the study
      criteria, 12 patients were enrolled between June 2003 and March 2007. Using three
      dimensional conformal partial breast irradiation, they received a conventional
      fraction of 2 Gy/fraction/day, 5 fractions/week, DT60 Gy. According to follow-up
      data collected in August 2010, the rates of local recurrence and distant
      metastasis were 0%. The most common adverse reactions included grade 2
      radioactive erythema in 2 (17%) cases and pigment deposition in 10 (83%). The
      results revealed that the patients exhibited good local tumor control, with minor
      adverse reactions and satisfactory cosmetic results. More samples and long-term
      observations are required to further assess the validity and feasibility of PBI.

PMID- 22977540
TI  - Antitumor effects of imatinib mesylate and synergistic cytotoxicity with an
      arsenic compound in neuroblastoma cell lines.
AB  - Neuroblastoma is a common tumor in childhood and exhibits heterogeneity and
      malignant progression. MYCN expression and amplification profiles are frequently
      correlated with the efficacy of therapy. Arsenic trioxide and imatinib mesylate
      (STI-571) have been suggested as promising therapeutic agents for neuroblastoma,
      which has been shown to be resistant to conventional therapy. In order to
      ascertain whether the combination of arsenic trioxide and STI-571 exerts a
      synergistic cytotoxic effect on neuroblastoma cells in relation to MYCN status,
      we evaluated cellular proliferation after 72 h of exposure to arsenic trioxide
      and STI-571 with or without siRNA against MYCN in SH-SY5Y, SK-N-SH and SK-N-BE(2)
      neuroblastoma cells. Arsenic trioxide and STI-571 demonstrated a synergistic
      inhibitory effect on cellular proliferation, while MYCN knockdown had an
      antagonistic effect on this combined treatment. These results indicate that STI
      571 treatment may prove effective for MYCN-expressing or MYCN-amplified
      neuroblastoma. Furthermore, siRNA therapy targeted to MYCN should be avoided in
      combination with STI-571 treatment in cases of neuroblastoma.

PMID- 22977541
TI  - Association of dynamic changes in serum cytokine levels with the severity of
      injury in patients suffering from closed chest traumas complicated with pulmonary
      contusions.
AB  - This study aimed to examine the dynamic changes in the serum levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10 in patients suffering
      from closed chest injuries and concomitant pulmonary contusions and their
      correlation with the Thoracic Trauma Severity Score (TTS) and Injury Severity
      Score (ISS). Patients with multiple traumas with an ISS >=16 (n=41) were
      evaluated in the study. Patients included 21 individuals with trauma complicated
      by pulmonary contusion and 20 patients with trauma without contusion. Venous
      blood samples were collected from the patients on days 1, 2, 3, 5 and 7 following
      trauma to assess serum levels of TNF-alpha, IL-6 and IL-10, whose correlation
      with TTS and ISS was analyzed. Levels of TNF-alpha, IL-6 and IL-10 remained
      significantly higher in the patients with trauma complicated by contusion
      compared to the patients with trauma without contusion (P<0.01). These three
      cytokines were positively correlated with TTS and ISS in the patients with trauma
      complicated by contusion. Serum TNF-alpha, IL-6 and IL-10 levels increased
      significantly in the patients with trauma complicated by pulmonary contusion. In
      conclusion, both cytokine assays and TTS facilitate the accurate assessment of
      the severity of chest injury.

PMID- 22977542
TI  - Pulmonary alveolar proteinosis and successful therapy with combined lavage
      procedures: Case reports.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the
      accumulation of lipoproteinaceous material within alveolar spaces. Whole-lung
      lavage (WLL) has been the most common therapeutic intervention for this disorder.
      However, patients presenting with PAP are usually hypoxemic or in poor clinical
      condition, and WLL may be impossible to perform. In such cases, multiple
      segmental lavage (MSL) may be advocated as a first-choice therapy prior to WLL.
      Herein, we present two cases with idiopathic PAP treated successfully with both
      lavage techniques consecutively. After the MSL procedure, WLL was performed, and
      both patients showed a marked clinical and physiologic improvement. Therefore,
      for patients who are not good candidates for general anesthesia, we recommend MSL
      (or 'prewash') before WLL to produce an increase in the blood oxygen level for
      long-duration general anesthesia. In the surgical room, close monitoring and
      repositioning of the patient as well as maintenance and inspection of the correct
      tube position, and manual chest wall percussion are extremely important for the
      safety and success of the procedure.

PMID- 22977543
TI  - Effective oral combination metronomic chemotherapy with low toxicity for the
      management of castration-resistant prostate cancer.
AB  - Prostate cancer (PC) was previously believed to be a chemoresistant disease. In
      recent years taxane-based chemotherapy has been shown to prolong survival in
      patients with castration-resistant prostate cancer (CRPC). It remains to be
      shown, however, which type of chemotherapy provides the most beneficial effect
      with the least amount of side effects. Seventeen patients with chemonaive CRPC
      were enrolled in a pilot study evaluating an orally administered chemo-hormonal
      treatment regimen using a weekly sequential combination called KEES; consisting
      of ketoconazole in combination with cyclophosphamide or etoposide in combination
      with estramustine administered on alternate weeks. Prednisone was administered
      throughout the treatment period. Prostate-specific antigen (PSA) response and
      acute and chronic toxicities were evaluated. Seventeen patients with CRPC were
      treated; eleven patients demonstrated a median reduction in PSA of 87% (range 26
      99%). Ten (59%) patients responded with a decrease in PSA >50%. Thrombocytopenia
      and anaemia were the most common side effects. One study fatality was reported,
      however, it was unclear whether this was treatment related. In conclusion, KEES
      may be a promising option for patients with CRPC, resulting in a clear reduction
      in PSA with limited toxicity. Further clinical evaluation of this metronomic
      chemohormonal combination is underway.

PMID- 22977544
TI  - Insulin-like growth factor receptor-1 expression predicts postoperative
      recurrence in adenocarcinoma of the lung.
AB  - Not all patients with lung cancer require postoperative adjuvant chemotherapy
      after a complete resection. However, no useful markers exist for either selecting
      appropriate candidates or for predicting clinical recurrence. The purpose of the
      present study was to clarify the clinical role of insulin-like growth factor
      receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from
      182 patients who underwent a complete resection for adenocarcinoma of the lung.
      The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status
      of the epidermal growth factor receptor (EGFR) and K-ras genes was also
      investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays
      were used to evaluate the MET gene association with tyrosine phosphorylation and
      hepatocyte growth factor (HGF) status, and amplification, respectively. Positive
      expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1
      expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with
      and without recurrence, respectively (p=0.009). Logistic regression models
      indicated that positive staining for IGFR1 expression was an independent factor
      associated with tumor recurrence. IGFR1 expression was associated with a poorer
      disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1
      expression to be independently associated with an increased risk for poor DFS.
      The tumors appearing positive for IGFR1 were more frequent among those with K-ras
      mutations when compared with the wild-type group. IGFR1 expression was associated
      with reduced DFS correlating with postoperative recurrence. Therefore, the
      expression status of IGFR1 can be a candidate surrogate marker to select patients
      who may benefit from adjuvant chemotherapy.

PMID- 22977545
TI  - Significance of aldehyde dehydrogenase 1 expression in stromal cells of diffuse
      large B-cell lymphoma.
AB  - Aldehyde dehydrogenase (ALDH) 1 is expressed in various stem/progenitor cells,
      including cancer-initiating cells (CICs). In the present study, ALDH1 expression
      was immunohistochemically examined in diffuse large B-cell lymphoma (DLBCL).
      Unexpectedly, ALDH1 expression was occasionally detected in stromal cells, but
      not in lymphoma cells. Positively stained cells were CD68(+) cells with
      voluminous cytoplasm and fascin(+) cells with reticular morphology, designated as
      macrophages and dendritic cells (DCs), respectively. The presence of ALDH1(+)
      macrophages was not correlated with stage, response to therapies and prognosis.
      However, cases with ALDH1(+) DCs were mostly nodal, which showed a poorer
      response to therapies and a worse overall survival rate than cases without
      ALDH1(+) DCs. The presence of ALDH1(+) DCs appears to be involved in the
      malignant potential of DLBCL in lymph node.

PMID- 22977546
TI  - Circulating endothelial progenitor cells in metronomic chemotherapy using
      irinotecan and/or bevacizumab for colon carcinoma: Study of their clinical
      significance.
AB  - The aim of the present study was to clarify the antitumor efficacy of metronomic
      chemotherapy using irinotecan (CPT-11) combined with or without bevacizumab
      against colon cancer, and the significance of circulating endothelial cell (CECs)
      and endothelial progenitor cells (CEPs) as a surrogate marker for metronomic
      chemotherapy. KM12SM cells were implanted into the subcutis of nude mouse. After
      confirming that the implanted tumors had grown 5 mm in size, group A received an
      intraperitoneal injection of 40 mg/kg CPT-11 every two weeks for 4 weeks
      [conventional maximum-tolerated dose (MTD)], group B received 10 mg/kg twice
      weekly (metronomic), group C received 10 mg/kg twice weekly combined with 5 mg/kg
      bevacizumab twice weekly (metronomic + anti-angiogenic), and the control group
      received 0.2 ml of PBS every week. Serial changes of CECs and CEPs in peripheral
      blood and microvessel density (MVD) in the tumor tissues were evaluated. The
      results showed that the antitumor activity in group B and in group C was
      significantly higher than that in group A. A significant inhibition in CEPs on
      day 15 in the metronomic therapy groups B and C was noted when compared to that
      in the control group, while there was no significant difference in CECs and CEPs
      between the groups on days 4 and 8. The MVD on day 15 in metronomic groups was
      significantly lower than that in group A. In conclusion, metronomic chemotherapy
      of CPT-11 with or without bevacizumab for colon cancer was more effective than
      the MTD therapy via anti-angiogenic effects. Sequential measurement of CEPs may
      be a predictive factor for the efficacy and a decisive factor for the optimal
      dose of metronomic therapy in colon cancer.

PMID- 22977547
TI  - Radiation-sensitizing effect of low-concentration docetaxel on human esophageal
      squamous cell carcinoma cell lines.
AB  - Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and
      chemotherapy than other cancers of the digestive system, and combined modality
      therapy may represent a promising treatment method. The radiation-sensitizing
      effect of docetaxel on ESCC cell lines was investigated. A colony formation assay
      was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to
      docetaxel (from 1.0*10(-11) to 10(-7) M) for 3 h to determine the concentration
      of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal
      concentration). Individual cell lines were then exposed to the non-cytocidal
      concentration of docetaxel prior to, during, and after irradiation to determine
      whether the timing of docetaxel administration affected cell survival. In
      addition, flow-cytometry was performed, and the cell cycle was examined prior to
      and after docetaxel exposure to assess the mechanism of docetaxel as a radiation
      sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with
      a different IC(50) for each cell type. Almost no cytocidal effect was observed at
      the following docetaxel concentrations: A431, <=1.0*10(-10) M; TE-2 and TE-3,
      <=1.0*10(-9) M. Concurrent treatment with docetaxel and radiation tended to
      decrease cell survival in all the cell lines compared with docetaxel or radiation
      alone. Cell survival was lowest when the cells were treated using X-ray
      irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in
      all three cell lines, docetaxel exposure increased the G2/M cell fraction with a
      higher increase in the cell line that exhibited the highest radiosensitivity.
      This study demonstrated that the administration of docetaxel at a non-cytocidal
      concentration prior to radiotherapy produced a synergistic cell-killing effect in
      SCC cell lines.

PMID- 22977548
TI  - Correlation of Kupffer cell function and hepatocyte function in chronic viral
      hepatitis evaluated with superparamagnetic iron oxide-enhanced magnetic resonance
      imaging and scintigraphy using technetium-99m-labelled galactosyl human serum
      albumin.
AB  - Kupffer cells contribute to the pathogenesis of liver injury in chronic liver
      disease, yet it is difficult to assess Kupffer cell function either ex vivo or in
      vivo, since supporting data are limited. The aim of this study was to clarify the
      relation between Kupffer cell function and hepatocyte function by analyzing the
      correlation between conventional indices of hepatic functional reserve and both
      superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) and technetium-99m
      galactosyl human serum albumin scintigraphy (Tc-99m-GSA) in patients with chronic
      viral hepatitis. Consecutive 46 patients (16 patients with chronic hepatitis and
      30 patients with cirrhosis) who underwent both SPIO-MRI and Tc-99m-GSA were
      examined. The patients were aged 46-83 years (median 70) and included 29 men and
      17 women. Spearman correlation coefficient was used to analyze the correlations
      between functional reserve indices and both reduction percentages of liver-to
      muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of
      Kupffer cell function and Tc-99m-GSA parameters. The usefulness of each parameter
      as a marker to differentiate Child-Pugh A from Child-Pugh B/C was evaluated using
      receiver operating characteristic (ROC) analysis. The reduction-%LMR correlated
      more closely with Child-Pugh score (r=0.77; P<0.001) than did Tc-99m-GSA
      parameters. For predicting Child-Pugh B/C, ROC analysis revealed that reduction
      %LMR (AUC=0.91, P<0.001) was the most useful parameter and at a cutoff value of
      50% or less, sensitivity, specificity, positive and negative predictive values
      were 0.79, 0.91, 0.94 and 0.71, respectively. SPIO-MRI may be a helpful non
      invasive method for the evaluation of hepatic functional reserve, and this study
      suggests that Kupffer cell function is closely correlated with hepatocyte
      function in patients with chronic viral hepatitis.

PMID- 22977549
TI  - Self-monitoring urinary salt excretion in adults: A novel education program for
      restricting dietary salt intake.
AB  - This study aimed to examine the usefulness of the self-monitoring of urinary salt
      excretion for educating individuals about the risk of excessive dietary salt
      intake. The subjects were 30 volunteers (15 men and 15 women) not consuming anti
      hypertensive medication. The subjects measured urinary salt excretion at home for
      4 weeks using a self-monitoring device. Blood pressure (BP), anthropometric
      variables and nutritional variables (by a dietary-habits questionnaire) were
      measured before and after the measurement of urinary salt excretion. Statistical
      analyses were performed, including paired t-tests, Chi-square test, Pearson's
      product moment correlation coefficient and multiple linear regression analysis.
      In all subjects, the average urinary salt excretion over 4 weeks was 8.05+/-1.61
      g/day and the range (maximum-minimum value) was 5.58+/-2.15 g/day. Salt excretion
      decreased significantly in weeks 3 and 4 (P<0.05 and P<0.01, respectively).
      Diastolic BP decreased from 77.7+/-14.3 (at baseline) to 74.3+/-13.3 after 4
      weeks (P<0.05), while systolic BP and anthropometric variables remained
      unchanged. Nutrition surveys indicated that energy intake was correlated with
      salt intake both before and after the measurements; changes in both variables
      during the observation period were correlated (r=0.40, P<0.05). The percentage of
      subjects who were aware of the restriction in dietary salt intake increased from
      47 to 90%. In conclusion, daily monitoring of the amount of urinary salt
      excretion using a self-monitoring device appears to be an effective educational
      tool for improving the quality of life of healthy adults.

PMID- 22977550
TI  - Bronchial reversibility with a short-acting beta2-agonist predicts the FEV1
      response to administration of a long-acting beta2-agonist with inhaled
      corticosteroids in patients with bronchial asthma.
AB  - A long-acting beta2-agonist (LABA) combined with an inhaled corticosteroid (ICS)
      is frequently prescribed as initial therapy in steroid-naive asthma patients
      because of its effective control of symptoms and improvement of pulmonary
      function. However, it is unclear which patients will be responsive to LABAs and
      whether bronchial responsiveness to LABAs is similar to that to short-acting
      beta2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present
      study was to compare the changes in spirometric parameters after SABA
      (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone
      propionate) therapy. Spirometric changes were evaluated as absolute values, as
      the percentage of predicted normal values and as the percentage of baseline
      values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients
      with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant
      improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow
      (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from
      baseline (expressed as the percentage predicted) in all patients. FEV1 and the
      FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were
      inversely related to the corresponding baseline values. Analysis of spirometric
      changes after SABA inhalation showed that FEV1 was the best among spirometric
      parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy.
      Reversibility of FEV1 with SABA inhalation predicts the spirometric response to
      LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy
      had a greater effect on bronchial reversibility in asthmatic patients, compared
      to SABA inhalation. This suggested that evaluation of bronchial reversibility
      after LABA/ICS therapy would be superior to that after SABA inhalation.

PMID- 22977551
TI  - 1,5-Anhydro-D-fructose: A natural antibiotic that inhibits the growth of gram
      positive bacteria and microbial biofilm formation to prevent nosocomial
      infection.
AB  - Nosocomial infections caused by microbial opportunistic infections or microbial
      biofilms may occur during hospitalization and increase patient morbidity,
      mortality and health care costs. Artificial antibiotic agents were initially used
      to prevent infection; however, the high prevalence of nosocomial infections has
      resulted in their excessive use, which has led to microbial resistance to these
      agents. The increase in microbial resistance to antibiotics and the development
      of antibiotic agents may be the cause of the production of other microbial
      resistance. Thus, natural compounds that have no adverse side effects would be a
      preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose
      (1,5-AF), a natural plant compound derived from starch, has been found to have
      multifunctional properties, including antioxidant, antiplatelet aggregation by
      thrombin and anti-inflammatory activities. The results of the present study
      demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci
      on the hands as well as the growth of Staphylococcus epidermidis, which is a
      cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm
      formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5
      AF is a natural compound that may be effective in preventing nosocomial
      infections, without causing adverse side effects.

PMID- 22977552
TI  - Turmeric and curcumin suppress presenilin 1 protein expression in Jurkat cells.
AB  - In the present study, we aimed to determine the effects of herbs or spices on the
      expression of presenilin 1, a molecule involved in gamma-secretase activity and
      the generation of amyloid-beta peptide in Alzheimer's disease. Western blot
      analysis revealed that presenilin 1 protein expression was down-regulated by
      stimulation with turmeric or cinnamon extracts in vitro, while the effects on
      presenilin 1 gene expression examined by reverse transcriptase-polymerase chain
      reaction were unaltered. Our results showed that curcumin, a component of
      turmeric, induced the down-regulation of presenilin 1 protein in Jurkat and K562
      cell lines.

PMID- 22977553
TI  - Cell budding from pre-invasive tumors: Intrinsic precursor of invasive breast
      lesions?
AB  - Our previous studies showed that in patients with ductal carcinoma in situ (DCIS)
      of the breast, the tumor cells that overlie focal myoepithelial cell layer
      disruptions (FMCLDs) are generally arranged as finger-like projections that bud
      into the stroma. These budding cells have significantly more genetic instability
      and invasion-related gene expression, and less estrogen receptor (ER) expression,
      than their epithelial cell counterparts. This study aimed to assess these cells
      for potential molecular markers that are uniquely associated with cell adhesion
      and motility. Seventeen ER-positive DCIS cases were screened by immunostaining
      for ER, and 7 cases which harbored FMCLD lesions were used to examine the
      expression of the potential markers. Two cases with both DCIS and invasive
      lesions were selected for comparing the differences in molecular expression
      between these lesion types. The results showed that expression levels of talin, E
      cadherin and focal adhesion kinase (FAK) in tumor cells overlying FMCLDs were
      higher than those within the corresponding duct. Integrin beta1 staining was
      detected only in a small number of the tumor cells overlying the FMCLDs. Vinculin
      staining was weak (18%) or not detected (82%), and no expression was found in the
      tumor cells within the corresponding duct or in the pure isolated DCIS. By
      contrast, the expression levels of talin, vinculin and integrin beta1 in the
      invasive tumors were distinctly higher than those in DCIS, and the expression of
      FAK and E-cadherin was lower. Using electron microscopy, we found that the tight
      junctions between tumor cells overlying the FMCLDs were reduced compared to the
      adjacent tumor cells in the lumen. These results indicate that the tumor cells
      overlying FMCLDs are likely to represent the specific precursors of invasive
      breast lesions. Our findings may also facilitate the identification of specific
      targets for further molecular profiling, which will more completely characterize
      this important cell population.

PMID- 22977554
TI  - Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute
      and chronic wounds.
AB  - The CCN family is a group of extremely cysteine-rich proteins that are found
      within the extracellular matrix and are comprised of cysteine-rich 61
      (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN 2) and nephroblastoma
      over-expressed (NOV/CCN3). Collectively, these proteins stimulate mitosis,
      adhesion, apoptosis, extracellular matrix production, growth arrest and
      migration, and regulate angiogenesis, tumour growth, placentation, implantation,
      embryogenesis and endochondral ossification. Despite such diverse activity, CCN
      protein function has not been explored in human wounds and healing. In the
      present study, we investigated the expression of these proteins in samples of
      normal, acute and chronic wounds using immunohistochemical staining and real-time
      quantitative RT-PCR. Statistical analysis was performed using the Fisher's exact
      test. Our results showed that, although all CCN proteins were present in normal,
      acute and chronic wounds, their expression levels differed, particularly in the
      case of connective tissue growth factor (CTGF), for which significantly reduced
      levels were found in chronic wounds compared to acute wounds (p<0.002). Thus, the
      lack of CTGF in wound tissues may contribute to the abnormal healing of clinical
      wounds. This suggests that CCN proteins may play an important role in human
      tissue wound healing. This further suggests that human wound healing may be
      promoted by manipulating the levels of this protein.

PMID- 22977555
TI  - Prognostic significance of phosphorylated signal transducer and activator of
      transcription 3 and suppressor of cytokine signaling 3 expression in
      hepatocellular carcinoma.
AB  - Altered expression of phosphorylated signal transducer and activator of
      transcription 3 (pSTAT3) and suppressor of cytokine signaling 3 (SOCS3) has been
      implicated in various types of human cancers. However, the clinical role of
      pSTAT3 and SOCS3 in hepatocellular carcinoma (HCC) is not well established.
      Immunohistochemical analysis of pSTAT3, SOCS3, Ki67 and VEGF expression was
      performed on tissue microarrays from 138 HCC patients. The expression of STAT3
      mRNA was further detected by in situ hybridization. The association of pSTAT3 and
      SOCS3 expression with clinicopathological factors and patient survival was
      analyzed. Altered expression of pSTAT3 and SOCS3 was observed in HCC specimens,
      compared to adjacent non-tumor tissue. Increased expression of pSTAT3 was
      correlated with large tumor size, higher clinical stage, Ki67 and VEGF
      expression, as well as poor patient survival. Decreased expression of SOCS3 was
      correlated with the expression of Ki67, VEGF and pSTAT3, and poor patient
      survival. Moreover, the expression of pSTAT3 was conversely correlated with SOCS3
      expression in HCC. Our results indicate that deregulated expression of pSTAT3 and
      SOCS3 may play roles in the development and progression of HCC. PSTAT3 and SOCS3
      should be further evaluated as potential novel biomarkers for HCC prognosis.

PMID- 22977556
TI  - Expression of cecropin B in Pichia pastoris and its bioactivity in vitro.
AB  - Natural cecropin B (CB), consisting of 35 amino acids, is a member of the
      cecropin family with the highest antibacterial activity. Here, a novel approach
      for the generation of recombinant CB in the methylotrophic yeast Pichia pastoris
      was explored. For this purpose, the CB gene was amplified by recursive PCR (rPCR)
      and cloned into the pPICZalphaA vector. The SacI-linearized plasmid pPICZalphaA
      CB was transformed into P. pastoris SMD1168 by electroporation. The expression of
      recombinant CB was induced with 1.0% methanol at pH 5.0 for 60 h at 28 degrees C.
      Recombinant CB was purified using cationic exchange chromatography; 5.0 mg of
      pure active CB was obtained from 100 ml of culture broth supernatant.
      Antimicrobial assays demonstrated that CB has a broad spectrum of antimicrobial
      activity against both Gram-positive and Gram-negative bacteria. Our results
      suggest that the P. pastoris expression system can be used to produce large
      quantities of fully functional CB for both research and industrial purposes.

PMID- 22977557
TI  - Endoscopic vs. conventional thyroidectomy for the treatment of benign thyroid
      tumors: A retrospective study of a 4-year experience.
AB  - Endoscopic thyroidectomy (ET) allows surgeons to remove a thyroid tumor from a
      remote site, while providing excellent results from a cosmetic viewpoint. The aim
      of this study was to explore the appropriateness and outcomes of ET via breast
      approach for the treatment of benign thyroid tumors. A total of 637 patients with
      benign thyroid tumors were recruited in our department. Two hundred and eighty
      five patients underwent the ET via breast approach (ET group) and 352 matched
      control patients underwent conventional thyroidectomy (ConT group). Variables,
      such as surgery-related outcomes and postoperative complications, were compared
      between these two groups. A unilateral lobectomy was performed in 126 patients
      (44.2%) of the ET group and in 163 patients (46.3%) of the ConT group. A
      bilateral total thyroidectomy was performed in 159 patients (55.8%) of the ET
      group and in 189 patients (53.7%) of the ConT group. The operative time in the ET
      group was longer compared to the ConT group (79.9+/-20.10 vs. 45.4+/-11.90 min,
      P<0.001, for unilateral lobectomy; and 89.9+/-14.60 vs. 60.0+/-8.44 min, P<0.001,
      for bilateral total thyroidectomy). The ET group had a significantly longer mean
      hospital stay compared to the ConT group (5.5+/-0.50 vs. 5.3+/-0.75 days,
      P=0.002). There was no case of conversion to conventional open surgery in the ET
      group. The recurrent laryngeal nerves and parathyroid glands were identified and
      protected in all cases. Our results indicate that ET performed via breast is a
      technically feasible and safe procedure with excellent cosmetic results for
      patients with benign thyroid tumors.

PMID- 22977558
TI  - Clinical implications and characteristics of factor forkhead box protein 3 in
      gastric cancer.
AB  - Transcription factor forkhead box protein 3 (FOXP3) is a specific marker of
      naturally occurring regulatory T cells (Tregs). Recently, various reports have
      suggested that FOXP3 may represent a tumor escape mechanism in cancer cells apart
      from its roles in Tregs. In the present study, the clinical and biological
      characteristics of FOXP3 were evaluated in human gastric cancer. The expression
      and localization of FOXP3 in gastric cancer cell lines was analyzed to evaluate
      its cellular biological features. Sections of human gastric cancer specimens were
      stained using immunohistochemistry (IHC) to assess the relationship between FOXP3
      expression and tumor differentiation, in order to identify its clinical
      characteristics in gastric cancer. Expression of FOXP3 mRNA and protein was found
      in four gastric cancer cell lines (AGS, SGC-7901, MKN-28 and MKN-45). IHC of the
      gastric cancer sections revealed that more than 56% of gastric cancers displayed
      nuclear or cytoplasmic FOXP3 staining. Furthermore, a linear relationship between
      the differentiation of the gastric cancer tissues and FOXP3 expression intensity
      was shown. IHC and confocal analysis showed that the expression of FOXP3 was
      mainly present in the nucleus of tumor cells in the tissues and cell lines. Thus,
      FOXP3 nuclear staining may be associated with the risk of poor tumor
      differentiation. Apart from the lymphocytes, no FOXP3 staining was noted in the
      normal gastric tissues and para-tumor tissues. The high frequency of FOXP3
      expression in gastric cancer tissue is a significant finding in the investigation
      of tumor differentiation and immune escape. This mechanism provides a further
      understanding of gastric cancer and a novel therapeutic strategy is presented.

PMID- 22977559
TI  - New perspective for nutritional support of cancer patients: Enteral/parenteral
      nutrition.
AB  - Cancer and its treatment result in severe biochemical and physiological
      alterations associated with a deterioration of quality of life (QoL). Cancer
      related malnutrition may evolve into cancer cachexia due to complex interactions
      between pro-inflammatory cytokines and the host metabolism. Depending on the type
      of cancer treatment (either curative or palliative), the clinical condition of
      the patient and nutritional status, adequate and patient-tailored nutritional
      intervention should be prescribed (diet counseling, oral supplementation, enteral
      or total parenteral nutrition). Nutritional support has been widely advocated as
      adjunctive therapy for a variety of underlying illnesses, including surgery and
      medical oncotherapy (radiation or chemotherapy for cancer). Glutamine, n-3 fatty
      acids and probiotics/prebiotics are therapeutic factors that potentially modulate
      gastrointestinal toxicity related to cancer treatments. Enteral and parenteral
      nutrition may help improve patient survival, functional status and QoL, yet the
      benefits appear to be primarily limited to patients with good functional status
      and with gastrointestinal disease affecting nutritional intake. Parenteral
      nutrition offers the possibility of increased or maintenance of the nutrient
      intake in patients for whom normal food intake is inadequate and for whom enteral
      nutrition is not feasible, is contraindicated or is not accepted by the patient.
      This article reviews evidence on issues relevant to enteral and parenteral
      nutrition in patients with cancer.

PMID- 22977560
TI  - Prognostic and predictive value of CEA and CYFRA 21-1 levels in advanced non
      small cell lung cancer patients treated with gefitinib or erlotinib.
AB  - The prognostic and predictive value of pre-treatment serum levels of
      carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were
      assessed in advanced non-small cell lung cancer (NSCLC) patients treated with
      gefitinib or erlotinib. Pre-treatment CEA and CYFRA 21-1 levels were measured in
      123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h
      CEA) were significantly associated with females, patients with adenocarcinoma and
      non-smokers. Low CYFRA 21-1 levels (l-CYFRA 21-1) were significantly associated
      with a good performance status (ECOG PS 0-1). The overall response rate (RR) was
      27.6%, and a higher RR was associated with adenocarcinoma, h-CEA, and epidermal
      growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly
      longer progression-free survival (PFS) (P=0.021). Patients with l-CYFRA 21-1 had
      significantly longer PFS and overall survival (OS) (P=0.006 and P<0.001,
      respectively). Notably, h-CEA and l-CYFRA 21-1 levels were associated with good
      prognosis in patients with unknown EGFR mutation status or patients with squamous
      cell carcinoma (P=0.021 and P=015, respectively). A good ECOG PS (HR=0.45,
      P=0.017), h-CEA (HR=0.41, P=0.007), l-CYFRA 21-1 (HR=0.52, P=0.025), and an EGFR
      mutation (HR=0.22, P<0.001) were independently predictive of a longer PFS. A good
      ECOG PS (HR=0.52, P=0.018), l-CYFRA 21-1 (HR=0.36, P=0.004), and EGFR mutation
      (HR=0.53, P=0.051) were independently predictive of longer OS. h-CEA and l-CYFRA
      21-1 may be prognostic and predictive serum markers for higher response and
      longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib,
      particularly in patients with unknown EGFR mutation status or patients with
      squamous cell carcinoma.

PMID- 22977561
TI  - Sessile serrated adenoma shares similar genetic and epigenetic features with
      microsatellite unstable colon cancer in a location-dependent manner.
AB  - Genetic and epigenetic features of sessile serrated adenoma (SSA), a precursor
      lesion to colon cancer with microsatellite instability (MSI), were investigated.
      The aim of this study was to clarify whether there are location-dependent genetic
      and epigenetic features in SSA. Twenty-two patients with proximal SSAs and 8 with
      distal SSAs were recruited. Twenty-two patients with tubular adenoma (TA) and 66
      with proximal colon cancer were studied for comparison. Genetic and epigenetic
      features were evaluated as BRAF and KRAS mutations, MSI, hMLH1 methylation and
      CpG island methylator phenotype (CIMP). BRAF mutation (p=0.007) and CIMP
      (p=0.012) were more frequently found in proximal than in distal SSAs.
      Furthermore, the KRAS mutation was found only in distal SSAs. In TAs, no location
      related molecular features were observed. All SSAs, TAs and 42 colon cancer
      lesions were microsatellite stable (MSS). Twenty-four colon cancer lesions
      exhibited MSI and had more frequent BRAF mutations (p<0.001), hMLH1 methylation
      (p<0.001) and CIMP (p<0.001). BRAF mutation occurred in only 9.5% of MSS cancers
      (p=0.01). In MSI cancers with the BRAF mutation, a higher correlation with CIMP
      (p=0.032) was observed. We demonstrated the distinct genetic and epigenetic
      features between proximal and distal SSAs. Similar genetic and epigenetic
      features were shared between proximal SSAs and proximal MSI cancers harboring the
      BRAF mutation. By contrast, our results allow the possibility of carcinogenesis
      in SSAs leading to MSS cancer with the BRAF mutation.

PMID- 22977562
TI  - A surprising diagnosis of pancreatitis with pseudocyst associated with sudden
      massive effusion.
AB  - This article describes the case of a 40 year-old man presenting with pleuritic
      pain on the right side, cough, sputum and sweating symptoms. He had smoked 40
      pack-years of cigarettes and consumed 140 ml alcohol/day for 20 years. Breath
      sounds were diminished at the right lung base. Chest X-ray showed right hemi
      diaphragm elevation and heterogeneous opacity on the right inferior zone.
      Antibiotherapy was commenced for possible diagnosis of pleuropnemonia. The
      patient developed dyspnea after a few days. Right hemithorax filled with a
      parabolic shadow was observed on the chest X-ray. Serosanguineous exudate was
      sampled. Very high levels of amylase and lipase levels were detected in the
      pleural fluid. Furthermore, magnetic resonance imaging revealed pancreatic
      pseudocyst near the left diaphragmatic crus. Four thousand milliliters of pleural
      fluid was drained using an intercostal drain within a 4-day period, and chest
      symptoms were relieved. Upon follow-up, suitable therapy for chronic pancreatitis
      was administered, and the patient was stable without any recurrence.

PMID- 22977563
TI  - Identification of novel molecular markers for detection of gastric cancer cells
      in the peripheral blood circulation using genome-wide microarray analysis.
AB  - Although metastasis or relapse is a leading cause of death for patients with
      gastric cancer, the hematogenous spread of cancer cells remains undetected at the
      time of initial therapy. The development of novel diagnostic molecular marker(s)
      to detect circulating gastric cancer cells is an issue of great clinical
      importance. We obtained peripheral blood samples from 10 patients with gastric
      cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis
      consisting of 30,000 genes or ESTs was carried out using eight gastric cancer
      tissues and normal gastric mucosae. We selected 53 genes up-regulated in gastric
      cancer compared to normal gastric mucosae from our microarray data set, and,
      among these, identified five candidate marker genes (TSPAN8, EPCAM, MMP12, MMP7
      and REG3A) which were not expressed in peripheral blood mononuclear cells (PBMCs)
      from 4 healthy volunteers. We further carried out semi-quantitative nested
      reverse transcription-polymerase chain reaction (RT-PCR) for HRH1, EGFR, CK20 and
      CEA in addition to the five newly identified genes using PBMCs of patients with
      gastric cancer, and found that expression of one or more genes out of the nine
      was detected in 80% of the patients with gastric cancer. Moreover, the numbers of
      genes expressed in PBMCs were <=2 and >=2 in all vascular invasion-negative cases
      and in 5 of 6 positive cases, respectively, showing significant differences
      between the two groups (P=0.041). Nested RT-PCR analysis for the set of nine
      marker genes using PBMCs may provide the potential for detection of circulating
      gastric cancer cells prior to metastasis formation in other organs.

PMID- 22977564
TI  - Interleukin-28B polymorphisms are associated with an early viral response in
      patients receiving hepatitis C therapy.
AB  - Prediction of the efficacy of pegylated interferon (PEG-IFN) plus ribavirin (RBV)
      therapy against hepatitis C (HCV) infection is valuable for determining its
      applications. This study investigated the relationship between the early response
      of HCV to PEG-IFN/RBV therapy and the inter-leukin (IL)-28B genetic polymorphism
      in patients with HCV infection. The genotypes of IL-28B rs8099917 T>G single
      nucleotide polymorphism were determined in 144 patients with HCV infection. Among
      them, 59 were treated with PEG-IFN/RBV. The frequency of IL-28B TT homozygosity
      was 75.2% in patients with HCV serotype 1 and 84.6% in patients with serotype 2.
      Multivariate analysis showed that IL-28B TT homozygosity (P=0.014) and the
      platelets number (P=0.030) was associated with the early suppression of HCV-RNA
      at 12 weeks after the start of PEG-IFN/RBV therapy. The IL-28B polymorphism was a
      significant pre-treatment predictor of the response to PEG-IFN/RBV therapy in
      patients with HCV infection.

PMID- 22977565
TI  - Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced
      cytotoxicity in human mesothelioma cells.
AB  - Malignant mesothelioma (MM) is an aggressive cancer with no effective treatment
      options. Enforced expression of the gap junction (GJ) component connexin 43
      (Cx43) increases the sensitivity of MM cells to cisplatin. Bowman-Birk protease
      inhibitor (BBI) induces the restoration of Cx43 in several types of tumor cells.
      In this study, we examined the capability of BBI to enhance the cytotoxic effect
      of cisplatin in MM cells via the induction of Cx43. Human MM H28 cells were used.
      Cell viability was evaluated by a WST-1 assay and proteasomal activity was
      determined by fluorometric analysis. Protein and mRNA levels were determined by
      immunoblot analysis and real-time RT-PCR, respectively. GJ function mediated by
      Cx43 was evaluated using the scrape-loading method. BBI effectively inhibited H28
      cell growth in a dose-dependent manner (200-400 MUg/ml). In parallel with the
      growth inhibition, Cx43 levels (mRNA and protein) and GJ function were elevated
      by BBI treatment. Knockdown of BBI-induced Cx43 by an antisense nucleotide
      treatment almost cancelled the growth inhibition. BBI enhanced cisplatin-induced
      cytotoxicity in H28 cells, and down-regulation of Cx43 by the antisense
      nucleotide treatment abrogated the enhancing effect of BBI. The induction of Cx43
      by BBI contributed to Src inactivation and subsequent induction of Bax.
      Furthermore, an Src inhibitor (SU6656) also enhanced cisplatin-induced
      cytotoxicity in H28 cells. These results suggest that BBI improves the cytotoxic
      efficacy of cisplatin in H28 cells via the inhibition of Src signaling.

PMID- 22977566
TI  - gamma-secretase inhibitor up-regulates vascular endothelial growth factor
      receptor-2 and endothelial nitric oxide synthase.
AB  - Although previous studies have shown that gamma-secretase inhibitors
      significantly suppress tumor growth via anti-angiogenesis, the mechanism involved
      in the regulation of tumor angiogenesis by gamma-secretase inhibitors has not
      been clearly understood. The objective of this study was to investigate the
      regulation of vascular endothelial growth factor receptor (VEGFR) and endothelial
      nitric oxide synthase (eNOS) by a gamma-secretase inhibitor in the H5V mouse
      microvascular endothelial cell line. H5V cells were cultured with different
      concentrations of the gamma-secretase inhibitor DAPT for 48 h and with 100
      MUmol/l DAPT at different incubation times. Protein and mRNA expression of VEGFR
      1, VEGFR-2, VEGFR-3 and eNOS was measured by Western blotting and real-time PCR,
      respectively. The VEGFR-2 kinase inhibitor was used to assess the role of VEGFR-2
      in eNOS regulation. We found that the gamma-secretase inhibitor DAPT increased
      protein and mRNA expression of VEGFR-2 and eNOS, but decreased VEGFR-1 expression
      and had no significant effect on VEGFR-3. Up-regulation of eNOS was blocked by
      the VEGFR-2 kinase inhibitor. In conclusion, the gamma-secretase inhibitor
      enhances VEGFR-2 and eNOS expression, and the up-regulation of eNOS is dependent
      on an increase in VEGFR-2. Thus, we suggest that administration of the gamma
      secretase inhibitor be combined with disruption of eNOS or interruption of VEGF
      signaling, which may improve the anti-angiogenic efficacy in tumor treatments.

PMID- 22977567
TI  - Formoterol and cancer muscle wasting in rats: Effects on muscle force and total
      physical activity.
AB  - Cancer cachexia occurs in the majority of cancer patients before death, and it is
      responsible for the death of 22% of cancer patients. One of the most relevant
      characteristics of cachexia is that of asthenia, which reflects significant
      muscle wasting noted in cachectic cancer patients The aim of the present study
      was to assess whether the beta(2)-adrenergic agonist formoterol is associated
      with an improvement in physiological parameters such as grip force and total
      physical activity in cachetic rats. Administration of the beta(2)-agonist
      formoterol (0.3 mg/kg for 7 days) in rats bearing Yoshida AH-130 ascites hepatoma
      tumors, a model which induces a strong loss of both body and muscle weight,
      resulted in a significant reversal of the muscle wasting process, as reflected by
      individual muscle weights. The anti-wasting effects of the drug were also
      observed in terms of total physical activity and grip force, thus resulting in an
      improvement in physical performance in cachectic tumor-bearing rats.

PMID- 22977568
TI  - Adoptive cellular therapy enhances the helper T cell response and reduces the
      number of regulatory T cells.
AB  - It remains to be clarified whether adoptive cellular therapy (ACT) in patients
      with advanced cancer, in whom strong immunosuppression and immune-escape
      mechanisms are established, has the potential to alter cytokine secretion from
      blood cells and affect the number of regulatory T cells (Tregs). In this study,
      the secretion of cytokines from peripheral blood cells and the number of
      peripheral blood Tregs were analyzed before and after ACT. Blood samples were
      collected from 109 consecutive cancer patients who received ACT, which consisted
      of anti-CD3 stimulated lymphokine-activated killer cells. For testing immune
      function, venous blood was obtained from patients before the start of therapy and
      after they had received 4 cycles of ACT. Of the 109 patients, 76 received ACT
      four times or more. All 109 blood samples at baseline and 76 follow-up samples
      were available. The secretion ability of various cytokines from peripheral blood
      cells was measured, as well as the number of peripheral blood Tregs. We found
      that the secretion ability of interferon (IFN)-gamma and tumor necrosis factor
      (TNF)-alpha was enhanced significantly after treatment, while the number of Tregs
      and the ratio of Treg to CD4 was significantly decreased. Overall survival in
      patients with increased IFN-gamma and TNF-alpha secretion after ACT was
      significantly longer. These findings suggest a potential therapeutic role for ACT
      in cancer immunotherapy.

PMID- 22977569
TI  - Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian
      populations.
AB  - We previously identified rs6929846 of the butyrophilin, subfamily 2, member A1
      gene (BTN2A1) as a susceptibility locus for myocardial infarction in Japanese
      individuals by a genome-wide association study. The aim of the present study was
      to examine the relation of the rs6929846 polymorphism of BTN2A1 to dyslipidemia
      in Japanese and Korean populations, given that dyslipidemia is an important risk
      factor for myocardial infarction. A total of 10,953 individuals from three
      independent subject panels were examined. The relations of the rs6929846
      polymorphism of BTN2A1 to serum concentrations of triglycerides, high-density
      lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were
      examined in each subject panel. The C->T polymorphism (rs6929846) of BTN2A1 was
      significantly associated with serum concentrations of triglycerides in Japanese
      subject panels A (P=0.0004) and B (P=0.0010), and in the Korean population
      (P=0.0095), with the minor T allele being related to an increased serum
      concentration of triglycerides. The rs6929846 was associated with serum
      concentrations of HDL-cholesterol in Japanese subject panels A (P=0.0047) and B
      (P=0.0015), with the T allele being related to a decreased serum concentration of
      HDL-cholesterol, but not in the Korean population. This polymorphism was
      associated with the serum concentration of LDL-cholesterol only in Japanese
      subject panel B (P=0.0059), with the T allele being related to an increased serum
      concentration of LDL-cholesterol. The results suggest that BTN2A1 may be a
      susceptibility gene for hypertriglyceridemia in East Asian populations and for
      low serum HDL-cholesterol in the Japanese population.

PMID- 22977570
TI  - Study of DNA methylation patterns of imprinted genes in children born after
      assisted reproductive technologies reveals no imprinting errors: A pilot study.
AB  - Assisted reproductive technology (ART) including in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) have been shown to be associated with
      abnormal genomic imprinting, thus increasing the incidence of imprinting
      disorders such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) in
      ART-conceived children. Furthermore, a recent study described abnormal DNA
      methylation in clinically normal children conceived by ART. However, data from
      different studies are conflicting or inconclusive. This study examined DNA
      methylation patterns of multiple imprinted genes in children born after ART to
      primarily evaluate the impact of ART on genomic imprinting. A total of 101
      newborns conceived by ART (40 ICSI and 61 IVF) and 60 naturally conceived
      newborns were involved in our study. After obtaining the approval of the
      Institutional Ethics Committee, umbilical cord blood was collected from each
      infant. Genomic DNA was isolated from each blood sample and treated using sodium
      bisulfite. Subsequently, using methylation-specific PCR (MS-PCR), we analyzed six
      differentially methylated regions (DMRs) including KvDMR1, SNRPN, MEST, MEG3,
      TNDM and XIST. Meanwhile, information regarding twin pregnancies, gestational
      age, and birth weight of the neonates was documented. None of the cases presented
      with phenotypic abnormalities. Children conceived by ART were more likely to have
      low birth weight and to be born before term, compared with children conceived
      spontaneously. However, 7 months to 3 years of clinical follow-up showed that
      none of the children had clinical symptoms of any imprinting diseases.
      Furthermore, the MS-PCR results showed that all 161 children had normal DNA
      methylation patterns at six DMRs despite the different mode of conception. Our
      data did not indicate a higher risk of DNA-methylation defects in children born
      after ART. However, further studies using quantitative methods are needed to
      confirm these results.

PMID- 22977571
TI  - Mutational analysis of the Kir6.1 gene in Chinese hypertensive patients treated
      with the novel ATP-sensitive potassium channel opener iptakalim.
AB  - Iptakalim is a novel K(ATP) opener with antihypertensive properties. The Kir6.1
      gene is one of the candidate genes that may influence the response to iptakalim
      in hypertensive patients. We aimed to ascertain whether a mutation in the coding
      region of the Kir6.1 gene is present in Chinese Han hypertensive patients. The
      study population included 162 Chinese Han hypertensive patients (81 men and 81
      women with a mean age of 55+/-9 years). Mutational analysis of the coding region
      of Kir6.1 was performed using PCR-SSCP and direct sequencing. No missense or
      nonsense mutations were found in these samples, while a single base pair
      substitution (C to T) at nucleotide position 111 in exon 2 of the coding region
      was noted in four patients (one female and three male), who were all heterozygous
      for the mutation. This C to T substitution did not result in an amino acid
      substitution (Ile37Ile, silent mutation). In the remaining 158 patients, no
      mutation was detected. The blood pressure of these four patients carrying the
      I37I polymorphism was well controlled by iptakalim. No mutation that alters the
      primary structure of Kir6.1 was detected in Chinese Han hypertensive patients.
      The results indicate that abnormality in the primary structure of Kir6.1 is not
      involved in the genetic pathogenesis of essential hypertension in Chinese Han
      hypertensive patients and has no effect on the BP response to iptakalim
      treatment.

PMID- 22977572
TI  - HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel
      therapy development.
AB  - Historically, clinical outcomes following spinal cord injury (SCI) have been
      dismal. Severe SCI leads to devastating neurological deficits, and there is no
      treatment available that restores the injury-induced loss of function to a degree
      that an independent life can be guaranteed. To address all the issues associated
      with SCI, a multidisciplinary approach is required, as it is unlikely that a
      single approach, such as surgical intervention, pharmacotherapy or cellular
      transplantation, will suffice. High mobility group box 1 (HMGB1) is an
      inflammatory cytokine. Various studies have shown that HMGB1 plays a critical
      role in SCI and that inhibition of HMGB1 release may be a novel therapeutic
      target for SCI and may support spinal cord repair. In addition, HMGB1 has been
      associated with graft rejection in the early phase. Therefore, HMGB1 may be a
      promising therapeutic target for SCI transplant patients. We hypothesize that
      inhibition of HMGB1 release rescues patients with SCI. Taken together, our
      findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA
      mediated HMGB1 could be administered for spinal cord repair in SCI patients.

PMID- 22977573
TI  - Potential of edaravone for neuroprotection in neurologic diseases that do not
      involve cerebral infarction.
AB  - Edaravone was originally developed as a potent free radical scavenger and has
      been widely used to treat cerebral infarction in Japan since 2001. Several free
      radical scavengers have been developed and some of them have progressed to
      clinical trials for the treatment of cerebral infarction. One such scavenger,
      edaravone, has been approved by the regulatory authority in Japan for the
      treatment of patients with cerebral infarction. Of particular interest is the
      ability of edaravone to diffuse into the central nervous system in various
      neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone
      has been found to have beneficial effects on inflammation, matrix
      metalloproteinases, nitric oxide production and apoptotic cell death.
      Concordantly, edaravone has been found to have neuroprotective effects in a
      number of animal models of disease, including stroke, spinal cord injury,
      traumatic brain injury, neurodegenerative diseases and brain tumors. The proven
      safety of edaravone following 9 years of use as a free radical scavenger suggests
      that it may have potential for development into an effective treatment of
      multiple neurologic conditions in humans.

PMID- 22977574
TI  - Polyamidoamine dendrimers as gene delivery carriers in the inner ear: How to
      improve transfection efficiency.
AB  - Hair cells in the cochlea can be damaged by various insults, including noise,
      drugs, infections and presbycusis, which may cause sensorineural hearing loss.
      Gene therapy is a novel therapeutic technology that, recently, has led to the
      idea of treating inner ear diseases on a genetic level. Depending on their
      characteristics, such as a high efficiency in delivery, the capability of
      specific targeting, multifunctionality, biodegradability, non-toxicity, non
      immunogenicity and the capability of limiting DNA degradation, nanovectors, such
      as polyamidoamine (PAMAM) dendrimers for cellular gene delivery, provide a
      promising approach to eradicate genetic diseases. They are a new class of highly
      branched spherical polymers that are highly soluble in aqueous solution. Their
      unique surface is composed of positively charged primary amine groups which allow
      them to form stable complexes with plasmid DNA, oligonucleotides, antibodies and
      drugs. This review provides an overview of the characteristics of PAMAMs which
      may be used in gene transfer into the cochlea as well as the efforts to improve
      their transfection efficiency as gene-delivery carriers.

PMID- 22977575
TI  - Accuracy of genotyping using the TaqMan PCR assay for single nucleotide
      polymorphisms responsible for thiopurine sensitivity in Japanese patients with
      inflammatory bowel disease.
AB  - Thiopurine drugs are the most common drugs used to maintain clinical remission in
      inflammatory bowel disease (IBD). Three single-nucleotide polymorphisms (SNPs),
      TPMT A719G (rs1142345), inosine triphosphate pyrophosphatase (ITPase) C94A
      (rs1127354) and multidrug resistance protein 4 MRP4 G2269A (rs3765534), have been
      reported to account for heightened sensitivity to thiopurine drugs in the
      Japanese population. We investigated the usefulness of the TaqMan((r)) PCR assay
      (Applied Biosystems) for the rapid detection of these SNPs to improve the safety
      of thiopurine therapy. We enrolled 44 healthy volunteers and 235 IBD patients.
      Genotyping of the SNPs was performed using Custom TaqMan SNP genotyping assays,
      direct sequencing and PCR-RFLP. Genotyping for MRP4 G2269A by the TaqMan PCR
      assay was successfully achieved in all samples. Comparison with our previous data
      using direct sequencing indicated one discordant result, and re-sequencing showed
      that the TaqMan PCR assay was correct. The overall accuracy of the TaqMan assay
      for MRP4 G2269A was 100%. The TaqMan PCR genotyping for TPMT A719G and ITPase
      C94A was successfully performed in all samples. The results of TPMT A719G by the
      TaqMan assay were identical with those of PCR-RFLP. In ITPase C94A, a comparison
      of the TaqMan assay and PCR-RFLP yielded 12 discordant results, and direct
      sequencing showed that the TaqMan PCR assay was correct. The allelic frequency
      determined by the TaqMan assay was 0.145 for MRP4 G2269A, 0.009 for TPMT A719G
      and 0.121 for ITPase C94A, respectively. In conclusion, the TaqMan((r)) PCR assay
      is useful for genotyping of SNPs responsible for thiopurine sensitivity in
      Japanese IBD patients.

PMID- 22977576
TI  - Expression of p-AKT and p-mTOR in a large series of bronchopulmonary
      neuroendocrine tumors.
AB  - Bronchopulmonary neuroendocrine tumors (BP-NETs) are separated into four
      subgroups: typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large
      cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC). The
      signaling pathway involving AKT/mammalian target of rapamycin (mTOR) is crucial
      to the regulation of cell growth, proliferation and survival, and is frequently
      activated in human cancers. Consequently, mTOR is considered an attractive target
      for anticancer agents. The present study aimed to evaluate the expression of
      phosphorylated AKT and mTOR in a series of BP-NETs, and to analyze the
      correlations with clinicopathological parameters. p-AKT and p-mTOR levels were
      determined by immunohistochemistry in a series of 210 BP-NETs, including 85
      SCLCs, 17 LCNECs, 26 ACs, 75 TCs and 7 tumorlets. Higher p-AKT and p-mTOR
      expression levels were identified in the majority of tumorlets and carcinoids in
      comparison to the LCNECs (P=0.0001) and SCLCs (P=0.0002). Furthermore, a
      significant association was observed between p-mTOR expression and tumor size (T)
      in SCLCs (P=0.04) and LCNECs (P=0.03): T3-T4 tumors exhibited significantly lower
      p-mTOR expression compared to T1-T2 tumors. In conclusion, most of the BP-NETs
      examined in this study expressed p-AKT and p-mTOR, suggesting that the AKT/mTOR
      pathway plays an important role in these tumors. Additionally, our results
      confirm that low- to intermediate-grade tumors are more closely associated to
      each other than to high-grade tumors, despite sharing common classification and a
      common origin from neuroendocrine cells. These findings improve our knowledge of
      the biological characterization of these tumors and indicate new therapeutic
      opportunities for the treatment of BP-NETs.

PMID- 22977577
TI  - Localization and characterization of lymphatic vessels in oral and cervical
      squamous cell carcinoma.
AB  - Lymph node metastasis is considered a factor in determining the prognosis of
      squamous cell carcinoma (SCC). Both oral and cervical SCC tumor cells prefer
      lymph vessels as the route of metastasis. D2-40 is a specific marker of lymphatic
      endothelial cells. This study clarifies the distribution and characteristics of
      lymphatic vessels in oral and cervical SCCs. Immunohistochemistry was performed
      in 20 oral and 20 cervical SCCs (10 non-metastatic and 10 metastatic to lymph
      nodes) using D2-40, CD31, CD34, CD105 and double staining with D2-40 and keratin.
      Lymphatic vessel density (LVD) was also determined morphologically. Results
      showed that lymphatic vessels in both types of SCCs were distributed mainly at
      the superficial region beneath the epithelium. The LVD in each tumor was
      significantly higher compared to the corresponding normal mucosa. Moreover, the
      LVD in lymph node metastasis in each tumor was significantly higher compared to
      their non-metastatic counterparts. Cancer cell invasion was observed in the
      lymphatic vessels suggesting the existence of lymph node involvement during
      metastasis. The new lymphatic vessels that proliferated around the cancer nests
      in both SCCs have endothelial cell characteristics inferred to be associated with
      early lymphatic development and initial dissemination of cancer cells.

PMID- 22977578
TI  - 17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy.
AB  - Numerous studies have attempted to identify gene expression profiles which can be
      utilized to predict responses to neoadjuvant chemotherapy (NAC), but their
      findings are not clinically applicable at present. In the present study, we
      sought to determine DNA copy number alterations (CNAs) in breast cancer tissues
      which are associated with the response to NAC. Frozen tumor tissues from 63
      breast cancer patients were obtained using core needle biopsy prior to NAC (3
      cycles of docetaxel plus adriamycin) and were microdissected. Array comparative
      genomic hybridization (array CGH) with 4,045 bacterial artificial chromosome
      (BAC) probes was performed to identify the CNAs. Changes in tumor size in
      response to NAC were measured via magnetic resonance imaging. Fluorescence in
      situ hybridization (FISH) was conducted to verify array CGH results and for
      independent validation studies. CNAs at eight chromosomal loci encompassing 24
      clones were correlated with changes in tumor size after NAC (p<0.05; t-test). Two
      CNAs were selected, 17p12 deletion and 17q21.32-33 gain, which were significantly
      associated with a smaller reduction in tumor size following NAC, via
      prioritization of the regions containing the candidate genes. In an independent
      validation set of samples from 39 patients, FISH assay further showed that the
      17p12 deletion was markedly associated with smaller changes in tumor size
      (p=0.006), while the 17q21.32-33 gain was not significant (p=0.309). In
      conclusion, we successfully identified a 17p12 deletion in breast cancer tissue
      which can be applied in predicting tumor resistance to NAC.

PMID- 22977579
TI  - Dentigerous cysts associated with impacted supernumerary teeth in the anterior
      maxilla.
AB  - Dentigerous cysts are thought to be caused by a developmental abnormality derived
      from the reduced enamel epithelium of the tooth forming organ. Most typical
      dentigerous cysts are those associated with the third molar teeth of the
      mandible, but rarely involve impacted supernumerary teeth in the anterior
      maxilla. Swelling and/or pain may be the major complaints of the patients.
      Herein, we review the literature spanning the past 22 years concerning
      dentigerous cysts associated with supernumerary teeth in the anterior maxilla,
      and present four additional cases with emphasis given to the clinicopathological
      characteristics of this type of dentigerous cyst.

PMID- 22977580
TI  - ERCC1 protein as a guide for individualized therapy of late-stage advanced non
      small cell lung cancer.
AB  - Excision repair cross-complementation group 1 (ERCC1) protein has been associated
      with cisplatin resistance. The objective of this study was to investigate the
      correlation between ERCC1 protein levels and the therapeutic effect of
      individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of
      190 advanced NSCLC patients were included in this study. Patients were randomized
      into either the individualized therapy group or the standard therapy group at a
      ratio of 2:1. Patients in the standard therapy group were treated with either
      gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1
      protein in lung cancer tissues of patients from the individualized therapy group
      was detected with immunohistochemistry. Patients with low ERCC1 levels received
      either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients
      with high levels received gemcitabine plus vinorelbine. The main outcome
      assessments were response rate (RR), overall survival (OS) and time to
      progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1
      year survival rate and TTP were not statistically significant. The median
      survival time was 10.10 months in the standard therapy group (95% CI 8.48-11.92)
      and 13.59 months in the individualized therapy group (95% CI 11.86-14.74). The
      difference in median survival time was significantly different between these
      groups (P=0.036). The median survival time was longer in the individualized group
      compared to the standard therapy group. ERCC1 protein expression in advanced
      NSCLC patients, however, was not significantly correlated with RR, OS and TTP in
      the individualized therapy group. Therefore, this study suggests that ERCC1
      protein levels should be assessed in combination with additional biomarkers to
      determine an optimal index for individualized therapy in advanced NSCLC patients.

PMID- 22977581
TI  - Non-Hodgkin's lymphoma of the testicle and bilateral adrenals detected by (18)F
      FDG PET/CT.
AB  - Lymphoma, particularly non-Hodgkin's lymphoma, may occur in sites other than the
      lymph nodes, i.e., extranodal lymphoma, which occurs in approximately 40% of
      total lymphoma cases. However, simultaneous detection of multiple extranodal
      involvements at presentation is quite uncommon. Here, we report a rare case of a
      55-year-old Chinese man with non-Hodgkin's lymphoma of the left testicle and
      bilateral adrenals as determined by (18)F-FDG PET/CT imaging. FDG PET/ CT has
      been successfully employed for lymphoma diagnosis, initial staging, restaging and
      therapy follow-up. It is useful for assessing both nodal and extranodal
      involvements. In the present case of lymphoma with involvement of the testicle
      and bilateral adrenals, (18)F-FDG PET/CT played an important role in the
      diagnosis and assessment of therapeutic response.

PMID- 22977582
TI  - Altered characteristics of cancer stem/initiating cells in a breast cancer cell
      line treated with persistent 5-FU chemotherapy.
AB  - Drug resistance of cancer stem/initiating cells has been considered to be one of
      the main reasons for tumor relapse. However, knowledge concerning the changes in
      stem/ initiating cells during chemotherapy is limited. In the present study, the
      breast cancer cell line MDA-MB-468 was cultured with 5-fluorouracil and serially
      passaged. Six cell generations were collected. Semi-quantitative RT-PCR and flow
      cytometric techniques were used to evaluate the protein and mRNA expression of
      stem/initiating factors (CD44(+)/CD24(-), Oct 3/4, SOX2 and beta-catenin), drug
      resistance genes (BCRP and MRP1) and an anti-apoptosis gene (survivin). The clone
      formation rate was also examined in every generation of cells. The results showed
      that, under conditions of persistent chemotherapy, the factors representing the
      quantity of stem/initiating cells (beta-catenin, Oct 3/4 and SOX2) followed a
      fluctuating trend of decrease-increase-further increase-decrease-increase
      decrease, and factors representing the proportion of stem/initiating cells
      (proportion of CD44(+)/CD24(-) and the clone formation rate) demonstrated a
      fluctuating trend of increase-further increase-further increase-decrease. The
      drug-resistance genes (BCRP and MRP1) and the anti-apoptosis gene (survivin)
      demonstrated a wave of increase-further increase-further increase-decrease
      increase (MRP1 decrease)-decrease. beta-catenin, Oct 3/4 and SOX2 showed a
      positive correlation (r=1, p<0.01). Our study confirmed that the drug resistance
      of cancer cells is mainly due to tumor stem/initiating cells, and that under
      conditions of persistent chemotherapy, the quantity or function of breast cancer
      stem/initiating cells increases and decreases alternately.

PMID- 22977583
TI  - Overexpression of activating transcription factor 5 in human rectal cancer.
AB  - The aim of this study was to investigate the relationship between the expression
      of activating transcription factor 5 (ATF5) and clinicopathological features in
      human rectal cancer. Relative quantitative real-time RT-PCR and
      immunohistochemical staining were used to detect ATF5 mRNA and protein expression
      in 92 paired samples of rectal cancer and distant normal tissues.
      Immunohistochemical staining of the matched rectal tissue samples revealed that
      the positive expression rate of the ATF5 protein in rectal cancer was
      significantly higher compared to that in the normal tissue. Furthermore, the
      expression of ATF5 in poorly differentiated cancers was higher compared to that
      in well to moderately differentiated cancers (P=0.013). However, there was no
      significant association between ATF5 protein expression and patient age, gender,
      histological tumor type, cell differentiation, invasive depth, lymph node
      metastasis or distant metastasis (P>0.05). However, to our surprise, there was no
      difference in the relative mRNA expression levels of ATF5 between normal tissues
      and rectal cancers. Our findings indicate that overexpression of ATF5 protein may
      be an important biomarker of the degree of malignancy, and increased expression
      may be related to the post-transcriptional regulation of ATF5 in rectal cancer
      tissues.

PMID- 22977584
TI  - Protective effect of erythropoietin on myocardial infarction in rats by
      inhibition of caspase-12 expression.
AB  - In the present study, the myocardial protective effects of erythropoietin (EPO)
      by inhibition of the expression of caspase-12 were investigated in a myocardial
      infarction rat model. Thirty male SD rats were divided into three groups: sham
      operation group, myocardial infarction group and EPO treatment group. The
      myocardial infarction model was created by ligating the left anterior descending
      coronary artery. The EPO treatment group was established by injecting rh-EPO
      (1,000 IU/kg) intraperitoneally every day after the operation, and the other two
      groups were injected with sodium chloride. Four weeks after induction of
      myocardial infarction, the left ventricular diastolic pressure (LVDP) was tested
      by Langendorff apparatus and the pathological changes were analyzed by H&E
      staining. Caspase-12 expression in the left ventricular myocardium was also
      measured by immunohistochemistry. Four weeks after induction of myocardial
      infarction, the improvement in heart function in the EPO treatment group was more
      distinct compared to that of the myocardial infarction group; LVDP was higher in
      the EPO treatment group compared to the myocardial infarction group, but lower
      compared to the control group. H&E staining showed that the myocardial cells in
      the normal control group were aligned in order with a clear structure and were
      stained equably, while the myocardial cells in the myocardial infarction model
      rats lined up in disorder with an augmented cell body appearing to have many
      granules and interstitial fibrosis. Myocardial fibrosis and disorder were
      improved in the EPO treatment group. The expression of caspase-12 in the
      myocardial infarction group was also increased compared to the EPO treatment
      group rats. The results suggest that EPO improves heart function in myocardial
      infarction rats by down-regulating the expression of caspase-12, which may
      protect the myocardium by abrogating endoplasmic reticulum stress-mediated
      cardiomyocyte apoptosis and improving heart function.

PMID- 22977585
TI  - Investigation of the protective effect of erythropoietin on spinal cord injury in
      rats.
AB  - Erythropoietin (EPO) is a promising therapeutic agent used in a variety of spinal
      cord injuries. Therefore, identifying the specific molecular pathway mediating
      the neuronal protective effect of EPO after spinal cord injury (SCI) is of great
      value to the patients concerned. Platelet-derived growth factor (PDGF)-B is an
      important factor in the recovery of neurological function. We explored changes in
      the expression of PDGF-B in spinal cord injury rats after receiving EPO
      treatment. We used a weight-drop contusion SCI model, and EPO treatment group
      rats received single doses of EPO (1,000 U/kg i.p.) immediately after the
      operation. Seven days after the operation, the results revealed a more rapid
      recovery as noted by the higher BBB scores, less disruption and more neuronal
      regeneration of the spinal cord in the EPO treatment group than that in the SCI
      group. PDGF-B expression also increased in the EPO treatment group compared to
      that in the SCI group (P<0.01). This study showed that PDGF-B plays a role in the
      neuronal protective effect of EPO on spinal cord injury in rats, which may help
      to explain the quick recovery after EPO treatment of spinal cord injury.

PMID- 22977586
TI  - Protective effect of Acer mono Max. sap on water immersion restraint stress
      induced gastric ulceration.
AB  - Acer mono Max. sap (AmMs) is called 'Gol-Li-Su' or 'Go-Lo-Soe' in Korean, which
      means 'water beneficial to the bones'. It is reported that the sap contains
      several types of minerals and sugars. In particular, the calcium concentration of
      the sap is 36.5 times higher than that of commercial mineral water. Apart from
      its anti-osteoporosis effect, no reports have addressed the biological activities
      of AmMs against degenerative diseases. In the present study, we investigated
      whether AmMs alleviates gastric ulcer-related symptoms in a stress-induced mouse
      model. To assess the effect of AmMs on gastric ulcer-like symptoms, we carried
      out a water immersion restraint (WIRE) test and found that AmMs has potential in
      alleviating gastric ulcers in a concentration-dependent manner. These results
      indicate that the nutritional factors of the sap mitigate the gastric ulcer
      related symptoms caused by stress-induced gastric lesions in mice. AmMs-treated
      mice exhibited a significant decrease in the ulcer index as compared to those
      treated with omeprazole or L-arginine. To examine one potential mechanism
      underlying this effect, we performed reverse transcription-polymerase chain
      reaction to ascertain whether molecular markers were associated with the
      mitigation of the gastric lesions. Epithelial and/or tissue nitric oxide synthase
      (NOS) was assessed to determine whether or not the genes were down-regulated dose
      dependently by the sap. The levels of these enzymes were found to be lower in the
      tissue samples treated with AmMs compared with the levels in the control samples.
      These findings collectively suggest that AmMs significantly protects the gastric
      mucosa against WIRE stress-induced gastric lesions, at least in part, by
      alleviating inducible NOS and/or neuronal NOS expression.

PMID- 22977587
TI  - Low-intensity ultrasound-induced cellular destruction and autophagy of
      nasopharyngeal carcinoma cells.
AB  - Ultrasound therapy, as a non-invasive modality, has been attracting extensive
      attention in the management of malignant tumors. The present study aimed to
      investigate low-intensity ultrasound-induced cellular destruction and autophagy
      in nasopharyngeal carcinoma cells in vitro. Nasopharyngeal carcinoma CNE2 cells
      were subjected to ultrasound exposure, as tumor model cells, at an intensity of
      1.35 W/cm(2). Cytotoxicity was investigated 24 h after ultrasound treatment.
      Nuclear damage was observed using nuclear staining with Hoechst 33258.
      Mitochondrial dysfunction was measured using confocal laser scanning microscopy
      with rhodamine123 staining. Mitochondrial morphology and autophagy were observed
      using transmission electron microscopy (TEM). Low-intensity ultrasound
      significantly killed CNE2 cells proportional to the ultrasonic treatment time.
      Upon nuclear staining, nuclear condensation and typical apoptotic bodies were
      noted in the CNE2 cells exposed to ultrasound wave for 12 sec. A collapse in
      mitochondrial membrane potential was noted in the treated cells. Upon TEM,
      swollen mitochondria, more vacuoles and autophagy were noted after ultrasound
      treatment. Our findings demonstrate that low-intensity ultrasound significantly
      damages CNE2 cells and emphasize that autophagy may be an important event in
      ultrasound-induced cell death.

PMID- 22977588
TI  - Prediction of clinical outcome using p16INK4a immunocytochemical expression in
      low-grade squamous intraepithelial lesions and high-risk HPV-positive atypical
      squamous cells of undetermined significance in patients with and without
      colposcopic evident cervical disease.
AB  - p16INK4a as a diagnostic marker of a cervical intraepithelial neoplasia of grade
      2+ (CIN2+) in atypical squamous cells of undetermined significance (ASC-US) and
      low-grade squamous intraepithelial lesion (LSIL) cytological samples has been
      analyzed, but has not yet been included in clinical routine practice. One hundred
      and ninety-one patients with an abnormal Pap test (84 ASC-US and 107 LSILs) who
      underwent colposcopy were selected for this study. At enrollment, 96 patients
      (Group 1) had a positive colposcopy and therefore underwent a cervical biopsy,
      while 95 (Group 2) had a negative colposcopy and were followed up for up to 1
      year. Both groups were tested for p16INK4a using immunocytochemical methods, and
      the p16INK4a results were correlated with histology or follow-up outcome. In
      Group 1 ASC-US cases, 82% of lesions less than CIN2 were p16INK4a-negative and
      all CIN2 cases were p16INK4a-positive (p=0.00044). In Group 1 LSIL cases, 71% of
      lesions less than CIN2 were p16INK4a-negative and 87% of CIN2/3 were p16INK4a
      positive (p=0.00033). Seventy-seven percent of Group 2 ASC-US patients with a
      negative 1-year follow-up (NF-U) were p16INK4a-negative at enrollment, while all
      patients with positive follow-up (PF-U) were p16INK4a-positive (p=0.00113). In
      Group 2 LSIL cases, 83% of patients with NF-U were p16INK4a-negative, while 65%
      of patients with PF-U were p16INK4a-positive at enrollment (p=0.0014). In fact,
      39% of the positive p16INK4a LSIL patients had CIN2+ histological lesions. The
      positive predictive value of p16INK4a for CIN2+ was 50% in ASC-US and 52% in LSIL
      cases; the negative predictive value was 100 and 94%, respectively. In
      conclusion, in our patients, a negative p16INK4a appears to be a marker of the
      absence of CIN3, while a positive p16INK4a can be correlated with the presence of
      histological CIN2+ found at enrollment or during the subsequent follow-up. Thus,
      its clinical predictive value is independent from the colposcopic aspect at
      enrollment.

PMID- 22977589
TI  - Costs and outcomes associated with hospitalized cancer patients with neutropenic
      complications: A retrospective study.
AB  - The average total hospitalization costs for adult cancer patients with
      neutropenic complications were quantified and the average length of hospital stay
      (LOS), all-cause mortality during hospitalization and reimbursement rates were
      determined. This observational retrospective cohort study identified adult
      patients with cancer who were hospitalized from January 2005 through June 2008
      using a large private US health care database (>342 inpatient facilities). ICD-9
      CM diagnosis codes identified patients by cancer type and who had neutropenic
      complications. The utilization and accounting systems of the hospitals were used
      to calculate mean (+/-95% confidence interval) hospitalization costs and LOS and
      percent all-cause mortality and reimbursement. Costs were adjusted to 2009 US
      dollars. There were 3,814 patients who had cancer and neutropenia, 1,809 (47.4%)
      also had an infection or fever and 1,188 (31.1%) had infection. Mean
      hospitalization costs were $18,042 (95% CI 16,997-19,087) for patients with
      neutropenia, $22,839 (95% CI 21,006-24,672) for patients with neutropenia plus
      infection or fever and $27,587 (95% CI 24,927-30,247) for patients with
      neutropenia plus infection. Mean LOS were 9 days (95% CI 8.7-9.3), 10.7 days (95%
      CI 10.2-11.2) and 12.6 days (95% CI 11.9-13.3), respectively. Mortality followed
      a similar trend; 8.3, 13.7 and 19.4%, respectively. By cancer type, hematologic
      malignancies had the highest average hospitalization costs and longest mean LOS
      of $52,579 (95% CI 42,183-62,975) and 20.3 days (95% CI 17.4-23.2), and a high
      mortality rate of 20.0%, while primary breast cancer patients had the lowest cost
      of $8,413 (95% CI 6,103-10,723), shortest LOS of 5.5 days (95% CI 4.2-6.8) and
      lowest mortality (0%). Mean reimbursement rates were 100.0, 101.5 and 95.4% for
      patients with neutropenia, neutropenia plus infection or fever and neutropenia
      plus infection, respectively. Hospitalized cancer patients with neutropenic
      complications had a higher all-cause mortality rate and higher inpatient
      hospitalization costs than those previously published. Results from this study
      suggest that costs for inpatient hospitalized cancer patients with neutropenic
      complications are principally reimbursed by payers.

PMID- 22977590
TI  - Single-incision laparoscopically assisted vaginal hysterectomy: Operative
      outcomes and its learning curve.
AB  - We previously reported on single-incision laparoscopic surgery applied to
      laparoscopically assisted vaginal hysterectomy (LAVH) cases. We accumulated
      single-incision LAVH cases to evaluate this operation, including its learning
      curve. Since July 2009, we planned to perform single-incision LAVH in 50 cases.
      Operative time, estimated blood loss, weight of resected uterus and additional
      procedures were recorded and compared to those of conventional multiport, multi
      incision LAVH. Additionally, 47 completed single-incision LAVH cases were divided
      into two groups; the former 24 cases and the latter 23 cases, to estimate its
      learning curve. Operative outcomes were statistically similar, except that more
      additional procedures were performed in the conventional LAVH group (27.7% in
      single-incision vs. 57.5% in the conventional group, P<0.01). We experienced
      three conversions to multiport surgery from single-incision LAVH, and no
      conversion case to 'open' total abdominal hysterectomy from conventional LAVH,
      which was not significantly different (3/50, 6% vs. 0/40, 0%, P=0.12). During the
      study period, operative time was significantly shortened from 73.0+/-17.6 min for
      the former 24 cases to 58.0+/-12.2 min for the latter 23 cases (P<0.01). There
      was no significant difference with respect to other operative outcomes between
      the two groups. Single-incision LAVH can be performed as effectively as
      conventional multiport LAVH with a short learning curve. We consider that single
      incision LAVH may be a promising alternative method for the treatment of certain
      patients with uterine myomas and adenomyosis as even a less invasive
      gynecological operation is required without visible scars.

PMID- 22977591
TI  - Enhancement of the efficacy of mitomycin C-mediated apoptosis in human colon
      cancer cells with RNAi-based thioredoxin reductase 1 deficiency.
AB  - Thioredoxin reductase 1 (Trr1) is an antioxidant and redox regulator that
      functions in governing the cellular redox state and survival against oxidative
      insults in mammals. However, this selenoprotein is also overexpressed in various
      forms of malignant cancers, leading to the hypothesis that Trr1 may be a
      potential target for cancer therapy. A quinone anti-cancer drug, mitomycin C
      (MMC), has been clinically used in the treatment of several types of tumors,
      including those of the colon. MMC exerts its activity via ROS induction and
      further results in DNA cross-linkage. To evaluate the significant role of Trr1 in
      MMC resistance in human colon cancer (RKO) cells, specific reduction in the
      expression of Trr1 was achieved using short-hairpin RNA (shRNA)-based
      interference. Our results showed that stable Trr1 shRNA knockdown manifested
      higher cellular susceptibility to MMC in comparison to that in wild-type cells.
      In addition, increased intracellular ROS accumulation appeared in the Trr1 shRNA
      knockdown cells compared to the RKO wild-type cells, in proportion to a
      relatively higher fraction of the DNA damage reporter protein phosphorylated
      histone 'gamma-H2AX'. Notably, a neutral comet assay demonstrated that DNA double
      strand breaks were highly induced in the Trr1-deficient cancer cells in the
      presence of MMC, presumably stimulating cancer cell death. Our results also
      revealed that MMC-induced apoptosis was associated with enhancement of oxidative
      damage to DNA. These results suggest that the specific knockdown of Trr1
      expression via shRNA vector interference technology may be a potent molecular
      strategy by which to enhance the effectiveness of MMC-mediated killing in human
      colon cancer cells, through acceleration of double-strand DNA damage-oxidative
      stress as a trigger for apoptosis. This implies that Trr1 may be a prime target
      for enhancing the effectiveness of MMC chemotherapy in combination with specific
      RNA interference.

PMID- 22977592
TI  - Prognostic value of an inflammation-based score in patients undergoing pre
      operative chemotherapy followed by surgery for esophageal cancer.
AB  - Recent studies have shown that the presence of systemic inflammation is
      associated with poor outcome in patients with malignancy. However, whether
      systemic inflammation affects the response to pre-operative therapy and survival
      of patients undergoing multimodal treatment for esophageal cancer is not clear.
      We studied 152 patients who underwent pre-operative chemotherapy followed by
      surgery for esophageal cancer. The correlation between various
      clinicopathological factors, including hematological markers of systemic
      inflammatory response, and survival or response to chemotherapy was examined.
      Among various hematological factors, leucocyte count, hemoglobin level, albumin
      level, neutrophil-lymphocyte ratio and CEA, but not serum concentration of C
      reactive protein, were significantly associated with survival. Multivariate
      analysis revealed that the clinical response to chemotherapy, number of
      metastatic lymph nodes, operative complications and systemic inflammation score
      (SI score), comprising leucocyte count, albumin and hemoglobin levels, were
      independent prognostic factors, and identified the SI score as the most
      significant prognostic factor. There was no significant relationship between
      hematological markers of systemic inflammation, including the SI score, and the
      response to chemotherapy. In conclusion, in patients scheduled for chemotherapy
      followed by surgery for esophageal cancer, systemic inflammation, reflected by
      SI, predicts poor outcome, but not the response to chemotherapy.

PMID- 22977593
TI  - Serum cytokine profiles in patients with prostate carcinoma.
AB  - It has been suggested that various cytokines are associated with the
      pathophysiology of prostate carcinoma (Pca). We profiled ten cytokines (IL-1beta,
      IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma and TNF-alpha) in the serum
      levels of 11 patients with organ-confined Pca, 15 with advanced Pca without
      cachexia, 8 with advanced Pca with cachexia (cachexia group) and 5 healthy males
      as controls. Cytokines were measured using a highly sensitive fluorescence
      microsphere system. Compared to the control group, serum levels of all cytokines
      were significantly higher in the cachexia group, and six cytokines (IL-1beta, IL
      2, IL-8, IL-12, TNF-alpha and IFN-gamma) were significantly higher in the group
      with advanced Pca without cachexia. In the group with organ-confined Pca, only IL
      1beta and IL-12 levels were significantly higher compared to the control group.
      In the cachexia group, levels of all cytokines apart from TNF-alpha were
      significantly higher compared to the group with organ-confined Pca, and levels of
      four cytokines (IL-2, IL-4, IL-8 and IL-10) were significantly higher compared to
      the group with advanced Pca without cachexia. These results indicate that i) an
      aberrance imbalance of cytokine production was associated with the
      pathophysiology of Pca and cachexia, ii) cytokine profiles in Pca patients were
      distinct by disease stage, and iii) IL-1beta and IL-12 may be applicable as early
      diagnostic indicators.

PMID- 22977594
TI  - Effect of a glucosamine-based combination supplement containing chondroitin
      sulfate and antioxidant micronutrients in subjects with symptomatic knee
      osteoarthritis: A pilot study.
AB  - In the present study, we aimed to investigate the potential effect of a
      glucosamine (1,200 mg/day)-based dietary supplement combined with chondroitin
      sulfate and three antioxidant micronutrients, namely methylsulfonylmethane, guava
      leaf extract, and vitamin D (test supplement) on osteoarthritis (OA) of the knee.
      A 16-week, randomized, double-blinded, placebo-controlled trial was conducted
      involving 32 subjects with symptomatic knee OA. Clinical outcomes were measured
      using the Japanese Knee Osteoarthritis Measure (JKOM) for symptoms and a study
      diary-based visual analog scale (diary VAS) for pain at baseline and at weeks 4,
      8, 12 and 16 during the 16-week intervention period. Furthermore, biomarkers for
      cartilage type II collagen degradation (C2C) and synovitis hyaluronan (HA) were
      measured. As compared with the baseline, the JKOM pain subscale was significantly
      improved at all of the four assessment time points in the test group, but was not
      at any time point in the placebo group. On the other hand, all of the four
      symptom subscales and the aggregated total symptoms were significantly improved
      in the two groups at one or more time points. However, all of these clinical
      improvements were greater in extent in the test group than in the placebo group,
      and there were significant differences between groups in the magnitude of changes
      from baseline for one subscale 'general activities' and the aggregated total
      symptoms at week 8 (P<0.05). The results of efficacy assessments with the diary
      VAS showed that all of the three pain subscales were significantly improved only
      in the test group at almost all the time points. Moreover, serum levels of C2C
      and HA were decreased by 10 and 25%, respectively, at week 16 in the test group,
      albeit not statistically significant, without any detectable changes in the
      placebo group. In conclusion, although the results obtained in this study were
      not conclusive, the tested glucosamine-based combination supplement is likely to
      have a beneficial effect on pain and other symptoms associated with knee OA.

PMID- 22977595
TI  - Intravesical administration of pirarubicin against superficial bladder cancer:
      Relationship between tumor tissue concentration and exposure time in the bladder
      or therapeutic effect.
AB  - The aim of this study was to investigate the relationship between tissue
      concentrations and exposure times or therapeutic effect of an anthracycline
      anticancer drug, pirarubicin, in bladder cancer tissue after single intravesical
      administration against superficial bladder cancer. The concentrations of
      pirarubicin in tumor tissues and serum were measured at designated collection
      times after a single intravesical administration of pirarubicin (30 mg) in 22
      patients with superficial bladder cancer. A wide range of concentrations of
      pirarubicin in bladder cancer tissue was observed (2.3-125 MUg/g of tissue),
      although serum pirarubicin concentrations were not detected in any of the
      patients. Recurrence of superficial bladder cancer after transurethral resection
      of the bladder tumor (TUR-BT) was observed in 2 patients (9%). The concentration
      of pirarubicin in the tumor tissue tended to be higher as the exposure time
      increased. There was a weak relationship between the pirarubicin tissue
      concentration and tumor size. However, no significant relationship between tissue
      pirarubicin concentrations and the prophylactic effect against intravesical
      recurrence of bladder cancer after TUR-BT was observed. All patients had no
      adverse events, such as bladder irritation and local toxicity, caused by the
      treatment with pirarubicin. These findings suggest that prior to single
      intravesical administration of pirarubicin to patients with superficial bladder
      cancer the exposure time and tumor size should be considered.

PMID- 22977596
TI  - Mucosal melanoma of the head and neck.
AB  - Mucosal melanoma of the head and neck (MMHN) is a rare malignant tumor associated
      with a poor prognosis. A retrospective study of case records of patients treated
      at our department between 1992 and 2010 was carried out. Thirteen patients were
      enrolled. The median age of the patients (3 males and 10 females) was 61 years
      (range 39-78). The median follow-up period was 48 months (range 10-115). Two
      common primary sites were the nasal cavity (8 cases) and sinonasal complex (5
      cases). Ten patients (77%) received curative surgery. Chemotherapy was
      administered to 10 patients. In addition, lymphokine-activated killer (LAK) cell
      therapy was administered to 7 patients as adjunctive immunotherapy after the
      initial treatment course. The overall 5-year, cause-specific survival rate was
      56%. Patients who received adjunctive LAK cell therapy had a survival rate of 67%
      at 5 years, while patients who did not receive adjunctive LAK cell treatment had
      a survival rate of 33%. MMHN is associated with a poor survival rate. The most
      common cause of death is distant metastasis. Surgery, radiotherapy and
      chemotherapy are common strategies for MMHN, but the control of metastasis is
      difficult. The use of immunotherapy remains uncommon for MMHN. However, from the
      viewpoint of a systemic disease, due to its high rate of metastases,
      immunotherapy using LAK cell treatment may contribute to the improvement of
      prognosis in patients with MMHN.

PMID- 22977597
TI  - Antitumor efficacy induced by a B16F10 tumor cell vaccine treated with
      mitoxantrone alone or in combination with reserpine and verapamil in mice.
AB  - An apoptotic tumor cell serves as a potential potent trigger for the initiation
      of naturally occurring tumor immunity. In the present study, a B16F10 tumor cell
      vaccine treated with mitoxantrone (MIT) was developed, and its antitumor effect
      on mice was evaluated. The results indicated that the B16F10 tumor cell vaccine
      treated with MIT alone or in combination with reserpine (RP) and verapamil (VP)
      for 12 h triggered apoptosis, and that the expression of CD80, the MHC II class
      molecule, NKG2D and its ligand were significantly increased compared to the
      expression levels in the control group. The tumor vaccine immunogenicity was
      significantly enhanced in the vaccinated mice, resulting in augmented
      cytotoxicity of splenocytes and NK cells as well as the splenocyte proliferative
      response compared to the control group mice. Notably, the mice vaccinated with
      the B16F10 tumor cell vaccine treated with MIT, RP and VP did not generate tumors
      only after 60 days into the observation, but the mice also generated a powerful
      immune prophylactic efficiency against the B16F10 tumor cell challenge. These
      findings demonstrated the safety and efficacy of the B16F10 tumor cell vaccine
      treated with MIT alone or in combination with RP and VP in the murine model, and
      suggest that an apoptotic tumor cell vaccine modeled on naturally occurring tumor
      immune responses in vivo may provide a safe and immunogenic tumor vaccine for
      potential applications in humans.

PMID- 22977598
TI  - Influence of a family history of breast and/or ovarian cancer on breast cancer
      outcomes.
AB  - Various published studies have been inconclusive in attempting to relate a family
      history of breast and/or ovarian cancer (BOC) to the survival of breast cancer
      patients. The aim of the study was to investigate the association of a family
      history of BOC with tumor characteristics, treatment response and the difference
      between the prognosis of familial breast cancer (FBC) patients and sporadic
      breast cancer (SBC) patients. Data on 348 operable FBC patients and 345 SBC
      patients were retrospectively analyzed. The overall survival (OS) and
      recurrence/metastasis-free survival (RFS) were compared for both groups. FBC
      cases were diagnosed at a relatively younger age (51.1+/-10.4 vs. 53.7+/-11.0
      years, P=0.054) and presented a lower T stage (P=0.000) than the SBC cases.
      Patients with a family history of BOC had a significantly greater risk of
      recurrence/metastasis (P= 0.04) and a non-significantly increased risk of death
      (P=0.06) compared to the SBC patients. In a multivariate analysis, family history
      of BOC was an independent predictive factor for both recurrence/metastasis rate
      (P=0.01, HR=0.012, 95% CI 0.02-0.57) and mortality (P=0.044, HR=0.43, 95% CI 0.19
      0.98) in the hormone receptor-positive population. Our results found that women
      diagnosed with FBC had an early onset of disease in the population studied, and
      the poor outcome of patients with a family history of BOC associated with
      survival was restricted to the hormone receptor-positive population.

PMID- 22977599
TI  - Human endogenous RNAs: Implications for the immunomodulation of Toll-like
      receptor 3.
AB  - Toll-like receptors (TLRs), a family of mammalian receptors, are able to
      recognize nucleic acids. TLR3 recognizes double-stranded (ds)RNA, a product of
      the replication of certain viruses. Polyinosinic-polycytidylic acid, referred to
      as poly(I:C), an analog of viral dsRNA, interacts with TLR3 thereby eliciting
      immunoinflammatory responses characteristic of viral infection or down-regulating
      the expression of chemokine receptor CXCR4. It is known that dsRNA also directly
      activates interferon (IFN)-induced enzymes, such as the RNA-dependent protein
      kinase (PKR). In the present study, the mRNA expression of TLR3, CXCR4, IFNgamma
      and PKR was investigated in a culture of peripheral blood mononuclear cells
      (PBMCs) stimulated with poly(I:C) and endogenous RNA from human PBMCs. No
      cytotoxic effect on the cells or on the proliferation of CD3(+), CD4(+) and
      CD8(+) cells was observed. TLR3 expression in the PBMCs in the presence of
      poly(I:C) was up-regulated 9.5-fold, and TLR3 expression in the PBMCs treated
      with endogenous RNA was down-regulated 1.8-fold (p=0.002). The same trend was
      observed for IFNgamma where in the presence of poly(I:C) an 8.7-fold increase was
      noted and in the presence of endogenous RNA a 3.1-fold decrease was observed. In
      the culture activated with poly(I:C), mRNA expression of CXCR4 increased 8.0-fold
      and expression of PKR increased 33.0-fold. Expression of these genes decreased in
      the culture treated with endogenous RNA when compared to the culture without
      stimulus. Thus, high expression of mRNA for TLR3, IFNgamma, CXCR4 and PKR was
      observed in the presence of poly(I:C) and low expression was observed in the
      cells cultured with endogenous RNA. In conclusion, TLR3 may play major
      physiological roles that are not in the context of viral infection. It is
      possible that RNA released from cells could contain enough double-stranded
      structures to regulate cell activation. The involvement of endogenous RNA in
      endogenous gene expression and its implications in the regulation thereof, are
      still being studied, and will have significant implications in the future.

PMID- 22977600
TI  - Vascular endothelial growth factor +936C/T polymorphism and gastric cancer risk:
      A meta-analysis.
AB  - The aim of this study was to determine whether the vascular endothelial growth
      factor (VEGF) +936C/T polymorphism confers susceptibility to gastric cancer (GC)
      by conducting a meta-analysis. Publications addressing the association between
      the VEGF +936C/T polymorphism and GC risk were selected from the Pubmed, Embase
      and CBM databases. Data were extracted from the studies by two independent
      reviewers. The meta-analysis was performed using RevMan 5.0.25 and STATA 9.2
      software. From these data, the odds ratio (OR) with 95% confidence interval (CI)
      was calculated. Finally, 8 case-control studies were retrieved reporting a total
      of 2,131 gastrointestinal cancer patients and 2,670 controls. Meta-analysis
      results showed that there was no significant association between the VEGF +936C/T
      polymorphism and GC risk in all comparisons of the T allele vs. C allele
      (OR=1.08, 95% CI 0.90-1.30, P=0.42), CT+TT vs. CC (OR=1.08, 95% CI 0.87-1.34,
      P=0.49), TT vs. CC+CT (OR=1.14, 95% CI 0.85-1.53, P=0.37), TT vs. CC (OR=1.18,
      95% CI 0.87-1.59, P=0.28) and TT vs. CT (OR=1.11, 95% CI 0.79-1.56, P=0.56). This
      meta-analysis confirms that there is a lack of association between the VEGF
      +936C/T polymorphism and GC risk.

PMID- 22977601
TI  - Epidemiological study of oral cancer patients in Alava province, Spain.
AB  - The authors conducted a retrospective study of oral squamous cell carcinoma
      (OSSC) patients in the province of Alava, Spain, to investigate the various
      epidemiological factors involved. The study included data on 30 patients referred
      to the Otolaryngology Department of our hospital. The authors identified
      epidemiological data, including age, symptoms, localization, tumor size, risk
      factors, tumor stage, treatment and outcome. An elevated percentage of risk
      factors was found, underlining the importance of early diagnosis. The highest
      prevalence was in the sixth decade of life. The most frequent symptom was pain,
      and the localization was in the tongue in 70% of cases. Tumor size ranged from 2
      to 3 cm, and 85% of patients underwent surgical resection. Risk factors of
      smoking and drinking affected 50% of the patients.

PMID- 22977602
TI  - Diagnostic value of neurotrophin expression in malignant pleural effusions.
AB  - Neurotrophins (NTs) modulate the growth of human malignancies, including lung
      cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve
      growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and
      4 (nT4)] levels for differentiating benign from malignant pleural exudates.
      Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%)
      exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine
      benign (9 infections and 50 inflammatory diseases) and 111 malignant (50
      extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were
      diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant
      than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC
      analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44
      pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of
      pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a
      higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in
      comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001).
      NTs and particularly BDNF may play a role in the pathogenesis of malignant
      pleural effusions.

PMID- 22977603
TI  - Oxidative stress markers may not be early markers of doxorubicin-induced
      cardiotoxicity in rabbits.
AB  - This study was performed to determine whether oxidative stress markers may be
      early markers of doxorubicin-induced cardiotoxicity. Forty-four male rabbits were
      randomly divided into four doxorubicin groups and one control group (8 rabbits).
      The control group received saline, and rabbits in the doxorubicin groups received
      2 mg/kg doxorubicin weekly for 1 (group 1, 8 rabbits), 2 (group 2, 8 rabbits), 4
      (group 3, 9 rabbits) or 8 (group 4, 11 rabbits) weeks. Echocardiography was
      performed to measure left ventricular ejection fraction, fractional shortening
      and the E/A ratio. Cardiotoxicity scores were determined by light microscopy
      using Billingham's method and by electron microscopy. Serum glutathione
      peroxidase (GPx) and superoxide dismutase (SOD) concentrations were quantified by
      a rabbit-specific enzyme-linked immunosorbent assay (ELISA). The Billingham
      cardiomyopathy scores for the rabbits in groups 3 or 4 were significantly higher
      (p<0.05) compared to the scores for the control group or groups 1 and 2.
      Myocardial injury was demonstrable by electron microscopy in groups 2, 3 and 4
      (p<0.05). Serum GPx concentrations decreased only in group 4 compared to the
      control group (p<0.05). No changes were measured in serum SOD concentration. The
      results indicate that oxidative stress markers may not be early markers of
      doxorubicin-induced cardiotoxicity.

PMID- 22977604
TI  - microRNA-450a targets DNA methyltransferase 3a in hepatocellular carcinoma.
AB  - microRNAs (miRNAs) have been proven to play key regulatory roles in
      hepatocarcinogenesis. In the present study, the possible role of microRNA-450a
      (miR-450a) in hepatocarcinogenesis was investigated. Our study revealed that miR
      450a was significantly down-regulated in hepatocellular carcinoma (HCC) tissues
      compared with that in normal liver (NL) and para-tumorous (PT) tissues, and miR
      450a expression in HepG2 cells was significantly lower than that in L02 cells.
      Both the mRNA and protein levels of the miR-450a potential target gene, DNA
      methyltransferase 3a (DNMT3a), were obviously higher in HCC compared with levels
      in the NL and PT tissues. We further identified DNMT3a as the direct target gene
      for miR-450a, and ectopic miR-450a expression in HepG2 cells caused the down
      regulation of DNMT3a and an inhibition of cell proliferation. Taken together,
      these findings suggest that miR-450a plays an important regulatory role in
      hepatocarcinogenesis through inhibition of DNMT3a expression, and miR-450a may be
      a potential target for the treatment of HCC.

PMID- 22977605
TI  - Irbesartan improves endothelial dysfunction, abnormal lipid profile, proteinuria
      and liver dysfunction in Zucker diabetic fatty rats independent of glucose and
      insulin levels.
AB  - Treatment with angiotensin type 1 receptor blockers (ARBs) is known to improve
      renal dysfunction and glucose metabolism in obese diabetic animal models and
      humans. This study examined the effects of irbesartan, a unique ARB with
      PPARgamma activation, on endothelial dysfunction, renal dysfunction, abnormal
      lipid profile, and liver dysfunction in obese fa/fa Zucker diabetic fatty (ZDF)
      rats. ZDF rats were administered irbesartan (30 mg/kg/day p.o.) for 12 weeks.
      Blood pressure, glucose metabolism, lipid profile and renal function were
      measured every 4 weeks. Response of mesenteric artery rings to acetylcholine was
      also evaluated as an index of endothelial function after 12 weeks of treatment.
      Although irbesartan did not affect glucose and insulin levels in both glucose and
      insulin tolerance tests, decreases in systolic blood pressure, dyslipidemia, and
      urinary protein excretion were noted from 4 weeks after the start of treatment
      and continued until 12 weeks. Endothelial and liver dysfunctions were also
      improved after 12 weeks of treatment. Compared to previous reports showing the
      effects of irbesartan at later time points such as 6 or 12 months, the present
      study demonstrated that a low-dose of irbesartan had favorable effects from the
      early period of treatment, independent of glucose metabolism. Our findings
      suggest that a low-dose of irbesartan improves diabetic complications quickly
      after starting treatment, and may support the use of irbesartan for preventing
      progression of diabetic complications.

PMID- 22977606
TI  - microRNA-101 inhibits lung cancer invasion through the regulation of enhancer of
      zeste homolog 2.
AB  - microRNAs (miRNAs) may function as oncogenes or tumor-suppressor genes depending
      on the targets that are regulated. Enhancer of zeste homolog 2 (EZH2) is the
      target of miR-101 and a member of the polycomb repressive complex 2, which is
      involved in the methylation of histone H3 at lysine 27 (H3K27). Therefore, we
      aimed to ascertain whether or not the overexpression of miR-101 inhibits invasion
      of lung cancer through regulation of EZH2. In this study, the expression of miR
      101 was down-regulated and the expression of EZH2 was up-regulated in lung
      cancer. Global methylation of H3K27 was higher in metastatic lung cancer than in
      early lung cancer lesions. Overexpression of miR-101 induced a marked reduction
      in EZH2 mRNA levels in several lung cancer cell lines. A reduction in the
      trimethyl H3K27 histone mark was detected at the CDH1 promoter in miR-101
      precursor-transfected cells. Moreover, the expression of CDH1 and MMP-2 was
      reversed by miR-101 transfection. Therefore, the overexpression of miR-101
      inhibits the invasiveness of lung cancer. miR-101 may be a potent tumor
      suppressor by altering chromatin structure through repression of EZH2 and may be
      a potential therapeutic tool for patients with lung cancer.

PMID- 22977607
TI  - Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in BXPC-3 and
      PANC-1 human pancreatic cancer cells.
AB  - Previous studies have shown that both pemetrexed, a cytotoxic drug, and
      erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR
      TKI), inhibit the cell growth of pancreatic cancer cells. However, whether they
      exert a synergistic antitumor effect on pancreatic cancer cells remains unknown.
      The present study aimed to assess the synergistic effect of erlotinib in
      combination with pemetrexed using different sequential administration schedules
      on the proliferation of human pancreatic cancer BXPC-3 and PANC-1 cells and to
      probe its cellular mechanism. The EGFR and K-ras gene mutation status was
      examined by quantitative PCR high-resolution melting (qPCR-HRM) analysis. BXPC-3
      and PANC-1 cells were incubated with pemetrexed and erlotinib using different
      administration schedules. MTT assay was used to determine cytotoxicity, and cell
      cycle distribution was determined by flow cytometry. The expression and
      phosphorylation of EGFR, HER3, AKT and MET were determined using Western
      blotting. Both pemetrexed and erlotinib inhibited the proliferation of BXPC-3 and
      PANC-1 cells in a dose- and time-dependent manner in vitro. Synergistic effects
      on cell proliferation were observed when pemetrexed was used in combination with
      erlotinib. The degree of the synergistic effects depended on the administration
      sequence, which was most obvious when erlotinib was sequentially administered at
      24-h interval following pemetrexed. Cell cycle studies revealed that pemetrexed
      induced S arrest and erlotinib induced G(0)/G(1) arrest. The sequential
      administration of erlotinib following pemetrexed induced S arrest. Western blot
      analyses showed that pemetrexed increased and erlotinib decreased the
      phosphorylation of EGFR, HER3 and AKT, respectively. However, both pemetrexed and
      erlotinib exerted no significant effects on the phosphorylation of c-MET. The
      phosphorylation of EGFR, HER3 and AKT was significantly suppressed by scheduled
      incubation with pemetrexed followed by erlotinib, but not by concomitant or
      sequential incubation with erlotinib followed by pemetrexed. In summary, our
      results demonstrated that the combined use of erlotinib and pemetrexed exhibited
      a strong synergism in BXPC-3 and PANC-1 cells. The inhibitory effects were
      strongest after sequential administration of pemetrexed followed by erlotinib.
      The synergistic effects may be related to activation of the EGFR/HER3/AKT pathway
      induced by pemetrexed.

PMID- 22977608
TI  - Glucocorticoids decrease body weight and food intake and inhibit appetite
      regulatory peptide expression in the hypothalamus of rats.
AB  - The aim of the present study was to investigate the effects of glucocorticoids
      (GCs) on appetite and gene expression of the hypothalamic appetite regulatory
      peptides, neuropeptide Y (NPY), agouti-related protein (AGRP) and cocaine and
      amphetamine-regulated transcript (CART), in non-obese and obese rats. Both non
      obese and obese rats were randomly assigned to three groups: normal saline, low-
      and high-dose GC groups (NSG, LDG and HDG, respectively), which received an
      intraperitoneal injection with normal saline (0.2 ml/100 g) or hydrocortisone
      sodium succinate at 5 and 15 mg/kg, respectively, for 20 days. The expression
      levels of NPY, AGRP and CART mRNA in the hypothalamus were measured by real-time
      quantitative PCR. Non-obese and obese rats were found to undergo weight loss
      after GC injection, and a higher degree of weight loss was observed in the HDG
      rats. The average and cumulative food intakes in the obese and non-obese rats
      injected with high-dose GC were lower compared to that in the NSG (p<0.05). mRNA
      expression levels of the orexigenic neuropeptides, NPY and AGRP, and the
      anorexigenic neuropeptide, CART, were significantly lower in the HDG than levels
      in the NSG for both the obese and non-obese rats (p<0.05). GC treatment decreased
      appetite and body weight, induced apparent glucolipid metabolic disturbances and
      hyperinsulinemia, while down-regulated mRNA expression levels of the orexigenic
      neuropeptides, NPY and AGRP, and anorexigenic neuropeptide, CART, in the
      hypothalamus in the rats. The mechanism which induces this neuropeptide
      expression requires further study.

PMID- 22977609
TI  - S-1 and the treatment of gastric cancer with peritoneal dissemination.
AB  - Peritoneal dissemination is the most common metastatic pattern of gastric cancer.
      We frequently face the necessity for gastrectomy in the event of gastric stenosis
      or gastric bleeding. However, the indication for palliative gastrectomy and the
      effectiveness of palliative chemotherapy are not clear. We retrospectively
      evaluated the prognostic factors after palliative gastrectomy in 121 gastric
      cancer patients with peritoneal dissemination. The expression of orotate
      phosphoribosyl transferase (OPRT) was examined immunohistochemically. The median
      survival time of all patients after palliative gastrectomy was 8.8 months. In the
      multivariate analyses, we adjusted the data of 82 patients without liver
      metastases for the background of 5-fluouracil (5-FU)-based chemotherapy regimen.
      The analysis revealed that the degree of peritoneal dissemination (multiple vs. a
      few metastases or cytology-positive; P= 0.01) and chemotherapy (S-1 vs. other 5
      FU; P=0.01) were independent predictors of survival. Particularly, S-1 treatment
      was associated with a more favorable prognosis of the patients with high levels
      of OPRT expression compared to that of the patients with low expression. Patients
      with peritoneal dissemination are considered as terminal and inoperable. However,
      S-1 treatment may improve the survival after palliative gastrectomy in patients
      selected according to the degree of peritoneal dissemination and high OPRT
      expression.

PMID- 22977610
TI  - Does duration of hysteroscopy increase the risk of disease recurrence in patients
      with endometrial cancer? A multi-centre trial.
AB  - Women with endometrial cancer often undergo hysteroscopy during their diagnostic
      work-up. Whether or not the duration of hysteroscopy affects the rate of positive
      peritoneal cells and the duration of recurrence-free survival is unknown. In a
      retrospective multi-centre study, the records of 552 patients with endometrial
      cancer were investigated. Duration of hysteroscopy was correlated with
      clinicopathological parameters and patient survival data. The mean [standard
      deviation (SD)] duration of hysteroscopy was 18.2 (10.5) min in the study
      population and 17.9 (10.1) min and 17.9 (10.2) min in patients with positive
      (n=109) and negative peritoneal cytology (n=443), respectively (p=0.9). There
      were no statistically significant correlations between duration of hysteroscopy
      and positive peritoneal cytology (p=0.6; rho=-0.028), FIGO stage (p=0.2; rho=
      0.080), lymph node involvement (p=0.2; rho=0.106) and patient age (p=0.5;
      rho=0.033). Longer duration of hysteroscopy (>15 min) was not associated with
      positive peritoneal cytology (yes vs. no, p=0.8), advanced tumour stage (FIGO I
      vs. II, III and IV, p=0.3), lymph node involvement (yes vs. no, p=0.1) and
      patient age (<=65 vs. >65 years, p=0.4). In a multivariate analysis, FIGO stage
      [p<0.0001; hazard ratio (HR)=5.1, 95% confidence interval (CI) 2.5-10.2], lymph
      node involvement (p=0.02; HR=3.2, 95% CI 1.2-8.8) and patient age (p=0.003;
      HR=2.4, 95% CI 1.3-4.2), but not duration of hysteroscopy (p=0.4; HR=1.2, 95% CI
      0.7-2.2), were associated with recurrence-free survival. We conclude that longer
      duration of hysteroscopy does not increase the risk of positive peritoneal
      cytology and it is not an adverse prognostic factor for recurrence-free survival
      in patients with endometrial cancer.

PMID- 22977611
TI  - Loss of heterozygosity analysis of microsatellites on multiple chromosome regions
      in dysplasia and squamous cell carcinoma of the esophagus.
AB  - The objective of this study was to characterize the molecular events in the
      carcinogenesis of esophageal squamous cell carcinoma (ESCC) and to identify
      biomarkers for early detection of the disease. Matched precancerous and cancerous
      tissues resected from 34 esophageal cancer patients from Chongqing, southern
      China, were compared to evaluate the extent of loss of heterozygosity (LOH).
      Sixteen microsatellite markers on chromosome regions 3p, 4p, 5q, 8p, 9p, 9q, 11p,
      13q and 17p were used for PCR-based LOH analysis. The overall frequency of LOH at
      the 16 microsatellite loci was significantly increased as the pathological status
      of the resection specimens changed from low-grade dysplasia (LGD) to high-grade
      dysplasia (HGD) and SCC (P<0.001). A total of 8 markers showed LOH in the LGD
      samples. In addition, heterozygosity was regained at 4 loci in the SCC samples of
      4 patients, respectively, in comparison to the results for these loci in the HGD
      samples. The overall rate of LOH increased significantly with the deterioration
      of the lesions, indicating that tumorigenesis of the esophageal squamous
      epithelia is a progressive process involving accumulative changes in LOH. The 8
      loci showing allelic loss in the LGD samples may be involved in the early-stage
      tumorigenesis of ESCC, and LOH analysis at these loci may help improve the early
      detection of this disease. Regain of heterozygosity found in certain patients
      suggests the possibility of genetic heterogeneity in the tumori-genesis of
      esophageal cancer.

PMID- 22977612
TI  - Long-term protective effects of the angiotensin receptor blocker telmisartan on
      epirubicin-induced inflammation, oxidative stress and myocardial dysfunction.
AB  - Chronic inflammation, oxidative stress and the renin-angiotensin system (RAS)
      play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan
      (TEL), an antagonist of the angiotensin II type-1 receptor, was found to reduce
      anthracycline (ANT)-induced CTX. We carried out a phase II placebo (PLA)
      controlled randomized trial to assess the possible role of TEL in the prevention
      of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients
      (mean age +/- SD, 53.0+/-8 years), cardiovascular disease-free with cancer at
      different sites and eligible for EPI-based treatment, were randomized to one of
      two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with
      Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum
      levels of proinflammatory cytokines, IL-6 and TNF-alpha, and oxidative stress
      parameters, reactive oxygen species (ROS) and glutathione peroxidase were
      determined. All assessments were carried out at baseline, after every 100 mg/m(2)
      of EPI dose and at the 12-month follow-up (FU). A significant reduction in the SR
      peak both in the TEL and PLA arms was observed at t(2) (cumulative dose of 200
      mg/m(2) of EPI) in comparison to t(0). Conversely, at t(3) (300 mg/m(2) EPI),
      t(4) (400 mg/m(2) EPI) and the 12-month FU, the SR increased reaching the normal
      range only in the TEL arm, while in the PLA arm the SR remained significantly
      lower as compared to t(0) (baseline). The differences between SR changes in the
      PLA and TEL arms were significant from 300 mg/m(2) EPI (t(3)) up to the 12-month
      FU. Serum levels of IL-6 increased significantly in the PLA arm at 200 mg/m(2)
      EPI (t(2)) in comparison to baseline, but remained unchanged in the TEL arm. The
      same trend was demonstrated for ROS levels which significantly increased at t(2)
      vs. baseline in the PLA arm, while remained unchanged in the TEL arm. The mean
      change in ROS and IL-6 at t(2) was significantly different between the two arms.
      In the present study, we confirmed at the 3-month FU a trend toward a decrease in
      ROS and IL-6 from t(2) in the PLA arm. Our results suggest that TEL is able to
      reverse acute (early) EPI-induced myocardial dysfunction and to maintain later a
      normal systolic function up to the 12-month FU. These effects are likely to be
      due to different mechanisms, RAS blockade and prevention of chronic
      inflammation/oxidative stress.

PMID- 22977613
TI  - DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect.
AB  - Ventricular septal defect (VSD) is the most comon form of congenital heart
      disease (CHD). DNA hypermethylation analysis may provide an insight into the
      molecular features and pathogenesis of this heart disease. Although aberrant DNA
      hypermethylation is implicated in the pathophysiology of this heart disease, only
      a limited number of genes are known to be epigenetically altered in VSD. We
      previously identified regulation of the NOX5 gene by hypermethylation in VSD
      fetuses by promoter methylation microarrays. This study was designed to detect
      the expression of NOX5 mRNA in VSD and normal fetuses. We also verified the
      results of promoter methylation microarrays by methylation-specific PCR. DNA
      extraction and nested methylation-specific PCR were performed on myocardial
      tissue samples from 21 VSD and 15 normal fetuses. The primers specific for
      methylated vs. unmethylated DNA were designed and amplified by nested PCR. The
      products were visualized on agarose gel. Hypermethylation of the NOX5 promoter
      was more frequent in VSD fetuses (66.67%) than in normal fetuses (20%). There was
      a significant concordance between NOX5 methylation and a decrease in its mRNA
      expression. Taken together, our results demonstrate that hypermethylation of the
      NOX5 gene may be involved in the pathogenesis of VSD.

PMID- 22977614
TI  - Functional dose-volume histograms for predicting radiation pneumonitis in locally
      advanced non-small cell lung cancer treated with late-course accelerated
      hyperfractionated radiotherapy.
AB  - The aim of this study was to determine whether functional dose-volume histograms
      (FDVHs) are valuable for predicting radiation pneumonitis (RP), and to identify
      whether FDVHs have advantages over conventional dose-volume histograms (DVHs) for
      the prediction of RP in patients with locally advanced non-small cell lung cancer
      (LANSCLC). Fifty-seven patients with LANSCLC undergoing functional image-guided
      late-course accelerated hyperfractionated radiotherapy were enrolled. The grade
      of RP was evaluated according to the Common Toxicity Criteria 3.0. To identify
      predictive factors of RP, the FDVHs, including the volume of the functional lung
      receiving 5 Gy (FV(5)) through 50 Gy (FV(50)), mean perfusion-weighted lung dose
      (MPWLD) and functional normal tissue complication probability (FNTCP), were
      analyzed and compared to their counterparts [total lung receiving 5 Gy (V(5))
      through 50 Gy (V(50)), mean lung dose (MLD) and normal tissue complication
      probability (NTCP)] derived from conventional DVHs. Univariate analysis revealed
      that V(5)-V(40), MLD, NTCP and FV(5)-FV(50), MPWLD, FNTCP were all statistically
      significant relative to the development of RP (all p<0.05). Multivariate analysis
      showed that only MLD and FV(15) were associated with RP (p=0.001 and 0.044,
      respectively). Receiver operator characteristic curve anaysis indicated that
      almost all of the FDVHs had larger areas under the curve compared to the DVHs,
      although no statistically significant difference was observed (p-value ranged
      from 0.066 to 0.951). FDVHs are valuable for predicting RP with the predictive
      efficiency equivalent to or slightly advantageous over conventional DVHs. More
      homogeneous studies involving larger numbers of patients are required to further
      assess the value of FDVHs for predicting RP.

PMID- 22977615
TI  - Bacterial diversity of subgingival plaque in 6 healthy Chinese individuals.
AB  - The subgingival microbial ecology is complex, and little is known regarding its
      bacteria species composition in healthy Chinese individuals. This study aimed to
      identify the subgingival microbiota from 6 healthy Chinese subjects. Subgingival
      samples from 6 volunteers were collected, the 16S rRNA gene was amplified using
      broad-range bacterial primers, and clone libraries were constructed. For the
      initial 2,439 sequences analyzed, 383 species-level operational taxonomic units
      (SLOTUs) belonging to seven phyla were identified, estimated as 51% [95%
      confidence interval (CI) 44-55] of the SLOTUs in this ecosystem. Most (85%) of
      the bacterial sequences, falling into 228 types of species, corresponded to known
      and cultivated species. However, 146 (6%) sequences, comprising 104 phylotypes,
      had <97% similarity to prior database sequences. Ten bacterial genera were
      conserved among all 6 individuals, comprising 2,000 (82%) of the 2,439 clones
      analyzed. Ten species were noted in all of the 6 subjects, comprising 1,435
      (58.8%) of the 2,439 clones. Streptococcus infantis was the species most
      frequently cloned. Furthermore, certain species which may participate in the
      pathogenesis of periodontal disease were present in the 6 subjects. Although the
      initial subgingival plaque community of each subject was unique in terms of
      diversity and composition, 10 common key species were found in the 6 Chinese
      individuals. These ten species of bacteria in the human subgingival plaque in the
      6 healthy individuals may be key species which, to some extent, affect
      periodontal health. Destruction of these key species in subgingival bacteria may
      break the microbiota balance and may easily lead to over-breeding conditions
      resulting in pathogenic oral disease.

PMID- 22977616
TI  - Adiponectin suppresses endoplasmic reticulum stress in nonalcoholic
      steatohepatitis.
AB  - In this study, we examined whether adiponectin suppresses endoplasmic reticulum
      (ER) stress in nonalcoholic steatohepatitis (NASH) using male transgenic mice
      expressing nSREBP-1c in adipose tissue, nSREBP-1c/adiponectin double-transgenic
      mice expressing human adiponectin in the liver, and wild-type male mice as the
      control. Histological findings similar to those observed in liver specimens from
      patients with NASH were observed in the livers from the nSREBP-1c transgenic mice
      at 30 weeks of age. By contrast, the NASH-like liver histology was markedly
      attenuated in age-matched nSREBP-1c/adiponectin double-transgenic mice. The
      nSREBP-1c/adiponectin double-transgenic mice showed human adiponectin production
      in the liver and a restored circulating human adiponectin level. Human
      adiponectin messenger ribonucleic acid (mRNA) expression in the liver was
      identified in the nSREBP-1c/adiponectin double-transgenic mice, but adiponectin
      receptor 1 and 2 mRNA expression in the liver was normal. TNFalpha mRNA was
      decreased in the liver of the nSREBP-1c/adiponectin double-transgenic mice
      compared with the nSREBP-1c transgenic mice. The protein expressions of X-box
      binding protein-1, activating transcription factor 4, acetyl-CoA carboxylase,
      TNFalpha and NFkappaB were down-regulated in liver tissues from the nSREBP
      1c/adiponectin double-transgenic mice. Mouse adiponectin and activating
      transcription factor 6 expressions were almost the same in the three groups. Post
      load plasma glucose levels were significantly lower in the nSREBP-1c/adiponectin
      double-transgenic mice compared with the nSREBP-1c transgenic mice. These results
      indicate that adiponectin expressed in the liver suppresses ER stress and
      attenuates hepatic steatosis, inflammation and insulin resistance in NASH.
      Adiponectin may open the way to novel therapies for human NASH.

PMID- 22977617
TI  - Expression profiling and identification of potential molecular targets for
      therapy in pulmonary large-cell neuroendocrine carcinoma.
AB  - The prognosis for patients with large-cell neuroendocrine carcinoma (LCNEC) of
      the lung is extremely poor, and an optimal treatment has not yet been
      established. It has been recently reported that molecular-targeted therapies,
      such as tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR),
      are effective in patients with lung carcinoma. In efforts to improve the
      prognosis of patients with LCNEC, we analyzed gene expression, gene mutations and
      immunohistochemical (IHC) expression of known molecular targets in LCNECs, and
      compared the expression to that of lung adenocarcinomas (ACs). Thirteen patients
      with primary LCNEC and 14 patients with AC were analyzed. We evaluated IHC
      expression for c-KIT, human epidermal growth factor receptor type 2 (HER2) and
      vascular endothelial growth factor (VEGF), gene mutations for EGFR, K-ras and c
      kit, and gene expression using fluorescence in situ hybridization for EGFR. In
      cases with LCNEC, the IHC expression of c-KIT, HER2 and VEGF was 76.9, 30.8 and
      100%, respectively. There was a significant difference in the IHC expression of c
      KIT and HER2 between the LCNEC and AC cases. Two cases of LCNEC had
      overexpression of HER2, and the frequency of EGFR gene mutations was higher in
      the the AC group, with only a single EGFR mutation (exon 18) identified in the
      LCNEC group. Although LCNEC had a higher rate of expression of c-KIT by IHC, no c
      kit gene mutations were found. These findings suggest a potential role for anti
      VEGF-, anti-c-KIT- and possibly anti-HER2-targeted agents in the treatment of
      LCNEC.

PMID- 22977618
TI  - Anti-vascular endothelial growth factor antibody single therapy for pancreatic
      neuroendocrine carcinoma exhibits a marked tumor growth-inhibitory effect.
AB  - At present, no effective chemotherapy for pancreatic neuroendocrine carcinoma
      (PNEC) exists. However, anti-angiogenic therapy is expected to be effective for
      PNEC, a hypervascular tumor. We treated PNEC and hypovascular pancreatic ductal
      cell carcinoma (DCC) cell lines with the anti-vascular endothelial growth factor
      (VEGF) antibody bevacizumab, and compared the antitumor effect between the two
      different types of cell lines. The PNEC cell line QGP-1 and the DCC cell lines
      BxPC-3 and AsPC-1 were used. We evaluated the ability of the cell lines to
      proliferate and secrete VEGF in vitro, the antitumor effect of bevacizumab
      administration in vivo and the side effects of bevacizumab on the pancreas in a
      caerulein-induced pancreatitis model. Comparison of the QGP-1 and DCC cell lines
      showed that QGP-1 secreted a higher level of VEGF under a hypoxic environment
      than the DCC cell line, and bevacizumab exerted the most marked growth-inhibitory
      effect on QGP-1; the number of intratumoral blood vessels decreased and the
      percentage of proliferating cells was approximately the same. In the pancreatitis
      model, bevacizumab administration did not adversely affect the pancreatitis or
      the associated hypoxic environment. Bevacizumab does not affect the pancreas
      itself; therefore, its potent inhibitory effect on the growth of pancreatic
      neuroendocrine tumors alone can be expected.

PMID- 22977619
TI  - Decreased expression of LMO7 and its clinicopathological significance in human
      lung adenocarcinoma.
AB  - LIM-domain only protein 7 (LMO7) has been suggested to act as a tumor suppressor
      for murine lung adenocarcinoma, while its splice variant p100 LMO7/#16 is
      associated with invasion and metastasis of rat AH130W1 cells. However, the
      importance of LMO7 in human lung cancer is unknown. We investigated LMO7 protein
      expression by immunohistochemistry in tumor tissues obtained from 57 patients
      with adenocarcinoma of the lung using a rabbit anti-LMO7 antibody. Signals for
      LMO7 were localized to the apical surface of the bronchial epithelium and to the
      cell membranes of pneumocytes in non-cancerous pulmonary tissues, but were noted
      circumferentially around the plasma membrane of cancer cells in all 57 patients
      with adenocarcinoma. The LMO7-positive group (24 patients, 42%) showed equivocal
      to strong expression of LMO7 in more than 50% cancer cells, while the remaining
      33 patients (58%) showed LMO7 expression in less than 50% of their cancer cells.
      The latter group had significantly more advanced disease than the LMO7-positive
      group with regard to T factor (p=0.011), nodal involvement (p=0.026) and p-stage
      (p=0.010; chi(2) test). Multivariate analysis using a logistic regression model
      showed that LMO7 expression was independently associated with the T factor
      (p=0.041). Kaplan-Meier analysis showed that a poor prognosis was associated with
      low expression of LMO7 (p=0.036; log-rank test). Our findings are consistent with
      earlier observations and demonstrate that LMO7 is inversely correlated with the
      development and prognosis of human lung adenocarcinoma.

PMID- 22977620
TI  - Long-term survival results and prognostic factors of early gastric cancer.
AB  - In spite of the favorable prognosis of early gastric cancer (EGC), recurrence or
      second primary cancers present in certain patients after curative surgery. It is
      crucial to identify who are at high risk and when. In the present study, 323
      patients with EGC who underwent curative surgery were studied. A total of 22
      patients (6.8%) died of recurrence, 9 patients (2.8%) died of a second primary
      cancer and 65 patients (20.1%) died of comorbid diseases during the 0.3-33 years
      of follow-up. Among the 22 patients with recurrence, hematogenous metastases were
      noted in over half of the cases (77.3%, 17/22); of these cases 15 patients had a
      recurrence within the first decade after surgery. Histological differentiation
      and nodal status were correlated with recurrence. Among the second primary
      cancers, remnant gastric, liver, lung and colon were the most common sites, and
      the second primary cancers primarily occurred in the second decade after surgery
      (6/9). Multivariate analysis identified nodal status (HR=4.20), vessel
      involvement (HR=3.40) and histological differentiation (HR=3.52) as independent
      prognostic factors for disease-free survival. However, gender, age and
      differentiation were independent influencing factors for overall survival.
      Comorbid diseases, recurrence and second primary cancers are the main cause of
      death in EGC patients after curative resection. Thus, treatment of comorbid
      diseases and a periodic follow-up schedule may contribute to improved prognosis.

PMID- 22977621
TI  - Combination of endoscopic submucosal dissection and chemoradiation therapy for
      superficial esophageal squamous cell carcinoma with submucosal invasion.
AB  - The efficacy, safety and clinical outcomes of a combination of endoscopic
      submucosal dissection (ESD) with subsequent chemoradiation therapy (CRT) for
      superficial esophageal squamous cell carcinomas (superficial ESCC) remain
      unclear. We assessed the outcome of the combination of ESD plus CRT for
      superficial ESCC. Fourteen patients with superficial ESCC invading into the
      muscularis mucosa or submucosa were treated with ESD plus CRT from 2004 to 2010.
      En bloc resection of the lesion was successfully performed in all patients. The
      mean diameter of the lesions was 25 mm (range 10-55). The distribution of the
      depth of tumor invasion was to the muscularis mucosa in 8 patients, to the upper
      submucosal third (sm1) in 4 patients and to the middle submucosal third (sm2) in
      2 patients. The laterally resected margins and vascular invasion were cancer
      negative in all patients, but lymph node involvement was detected in 2 patients.
      The mean follow-up period after CRT was 45 months (range 19-70). No patients died
      of esophageal cancer. Recurrence or metastasis of the esophageal cancer was not
      observed in any of the patients. The combination of ESD plus CRT is effective for
      superficial ESCC.

PMID- 22977622
TI  - Papillary lesions of the breast diagnosed using core needle biopsies.
AB  - Papillary lesions of the breast include a broad spectrum of lesions, from benign
      papillomas to papillary carcinomas. It is difficult to determine whether a lesion
      is benign or malignant based on the fragmented material of a core needle biopsy
      (CNB). This study evaluated patients with papillary lesions examined using CNB.
      We retrospectively reviewed 31 papillary lesions diagnosed using CNB between 2004
      and 2007. The clinical findings of benign and malignant papillary lesions were
      compared. The average patient age was 48.9 years. Twelve patients presented with
      a discharge and 10 patients presented with a lump. Eight patients were
      asymptomatic. The initial diagnoses by CNB of the 31 lesions were 25 intraductal
      papillomas, 4 intracystic papillomas and 2 adenomas. After CNB, excisional
      biopsies were performed in 23 patients and biopsies with a Mammotome((r)) in 2
      patients. Seven patients underwent regular follow-up. Five (16%) of the 31
      patients with papillary lesions were ultimately diagnosed with breast cancer. The
      average distance from the nipple to a tumor diagnosed as malignant was 2.46 cm,
      which was longer than for a tumor diagnosed as benign. Ultimately, 5 papillary
      lesions (16%) were diagnosed as breast cancer. To avoid overlooking a malignancy,
      surgical excision is advantageous for papillary lesions, particularly those
      located far from the nipple.

PMID- 22977623
TI  - Prediction of postoperative exacerbation of interstitial pneumonia in patients
      with lung cancer and interstitial lung disease.
AB  - Postoperative exacerbation of interstitial pneumonia in patients with lung cancer
      and interstitial lung disease has emerged as a serious problem. Therefore, the
      risk factors for postoperative exacerbation of interstitial pneumonia in patients
      with interstitial lung disease must be identified. We analyzed 22 patients
      diagnosed as having lung cancer with interstitial lung disease who underwent
      surgical treatment at the Kitasato University Hospital. Among the patients with
      lung cancer and interstitial lung disease, 5 patients (22.7%) had postoperative
      exacerbation of interstitial pneumonia. The prognosis of the patients with
      postoperative exacerbation was significantly poorer than that of patients
      without. Patients with postoperative exacerbation had a significantly higher age
      (>=75 years) and a significantly lower frequency of postoperative administration
      of steroid than patients without postoperative exacerbation. Almost all patients
      with postoperative exacerbation underwent lobectomy, had elevated KL-6 levels in
      the serum pre-operatively, and had significantly advanced stages of disease. Of
      the 5 patients with postoperative exacerbation, 2 had a history of inflammation
      prior to their exacerbation: 1 had a common cold and the other pyothorax. In
      patients with lung cancer and interstitial lung disease, advanced age, advanced
      stage disease, no postoperative administration of steroid and a pre-operative
      episode of inflammation are all risk factors for postoperative exacerbation of
      interstitial pneumonia.

PMID- 22977624
TI  - Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA
      expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation
      of metabolic syndrome, which is known to be associated with insulin resistance
      (IR). NAFLD occurs when the rate of hepatic fatty acid uptake from plasma and de
      novo fatty acid synthesis is greater than the rate of fatty acid oxidation and
      excretion as very low-density lipoprotein (VLDL). To estimate the effects of IR
      on hepatic lipid excretion, mRNA expression levels of genes involved in VLDL
      assembly were analyzed in NAFLD liver. Twenty-two histologically proven NAFLD
      patients and 10 healthy control subjects were enrolled in this study. mRNA was
      extracted from liver biopsy samples and real-time PCR was performed to quantify
      the expression levels of apolipoprotein B (apoB), microsomal triglyceride
      transfer protein (MTP) and liver fatty-acid binding protein (L-FABP). Hepatic
      expression levels of the genes were compared between NAFLD patients and control
      subjects. In NAFLD patients, we also examined correlations between expression
      levels of the genes and metabolic factors, including IR, and the extent of
      obesity and hepatic lipid accumulation. Hepatic expression levels of apoB, MTP
      and L-FABP were significantly up-regulated in NAFLD patients compared to control
      subjects. The expression levels of MTP were correlated with those of apoB, but
      not with those of L-FABP. In the NAFLD liver, the expression levels of MTP were
      significantly reduced in patients with HOMA-IR >2.5. In addition, a significant
      reduction in MTP expression was observed in livers with advanced steatosis.
      Enhanced expression of genes involved in VLDL assembly may be promoted to release
      excess lipid from NAFLD livers. However, the progression of IR and hepatic
      steatosis may attenuate this compensatory process.

PMID- 22977625
TI  - Clinical features of ovarian large-cell neuroendocrine carcinoma: Four case
      reports and review of the literature.
AB  - The objective of the present study was to present 4 recently encountered ovarian
      large-cell neuroendocrine carcinoma (LCNEC) cases, and to evaluate their
      clinicopathological features in the context of the previously reported 29 LCNEC
      cases. First, we described the clinical features of 4 recently encountered cases.
      Routine H&E staining and immunohistochemistry for CD56, synaptophysin and
      chromogranin A were performed on sections of both the LCNEC and epithelial
      carcinoma components. Clinical data for the total of 33 LCNEC cases were
      summarized, and the Kaplan-Meier survival curve was estimated. Our cases were
      observed in women aged 42-81 years. One case is clinically classified as FIGO
      stage IV with multiple metastases, and the others are classified as FIGO stages
      Ic, IIc and IIIb by post-surgical findings. Pathological features, assessed by
      H&E staining, were similar to lung LCNEC, and at least one neuroendocrine marker
      was positive staining in both LCNEC and the epithelial component. One case was
      pure type LCNEC and the others were mixed carcinoma. Paclitaxel/carboplatin
      chemotherapy was performed for all cases and 3 of the 4 treatments were
      effective. The prognoses of our cases were as follows: 1 in stage Ic died from
      the disease after only 2 months, but the others survived, with or without
      recurrence, for 32-64 months, whereas the total 5-year survival of the 33 LCNEC
      cases was 34.9%. In summary, our 3 LCNEC cases revealed ordinary chemo
      sensitivity, resulting in a better prognosis than those previously described,
      apart from 1 case which exhibited aggressive behavior. For the future, a
      retrospective survey to elucidate the prognostic factors and prospective clinical
      studies to evaluate the efficacy of treatment modalities of ovarian LCNEC are
      necessary, particularly for aggressive LCNEC cases.

PMID- 22977626
TI  - Combined inhibition of insulin-like growth factor-1 receptor enhances the effects
      of gefitinib in a human non-small cell lung cancer resistant cell line.
AB  - The type I insulin-like growth factor receptor (IGF-1R) signaling pathway is an
      important growth-regulatory pathway that is prevalent in a variety of cancer
      types, including human non-small cell lung cancer (NSCLC). To observe the
      combined effects of gefitinib and AG1024-induced IGF-1R inhibition on the growth
      of NSCLC, PC9/G cells, a NSCLC cell line with acquired resistance to gefitinib,
      were treated with AG1024 and gefitinib, alone or in combination. The
      proliferative activity of PC9/G cells upon different treatments was assessed by
      CCK-8, and the median-effects principle was used to assess the effect of the
      combined treatment. Apoptotic rates of the PC9/G cells for the different
      treatment groups were analyzed by flow cytometry. The expression of
      phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated-Akt (p
      Akt), and phosphorylated extracellular signal-regulated kinase (p-ERK) in PC9/G
      cells was examined by Western blotting. PC9/G cells exhibited apoptotic features
      after treatment with AG1024 and gefitinib alone, and their proliferation rates
      were inhibited to different degrees. The treatment of AG1024 combined with
      gefitinib resulted in a synergistic effect in inducing apoptosis, inhibiting cell
      proliferation and decreasing the expression of p-EGFR, p-Akt and p-ERK. In
      conclusion, combined inhibition of IGF-1R signaling enhances the anti
      proliferative and pro-apoptotic effects of gefitinib in NSCLC gefinitib-resistant
      cells. Moreover, the addition of an anti-IGF-1R strategy to gefitinib treatment
      may be more effective than a single-agent approach.

PMID- 22977627
TI  - Impact of dihydropyrimidine dehydrogenase and gamma-glutamyl hydrolase on the
      outcomes of patients treated with gemcitabine or S-1 as adjuvant chemotherapy for
      advanced pancreatic cancer.
AB  - Gene expression analyses may play useful roles in determining the prognosis of
      cancer patients and in selecting antitumor drugs. This retrospective study
      examined potential prognostic factors in patients with pancreatic cancer who
      received adjuvant chemotherapy after surgery. The study group consisted of 79
      patients who had received gemcitabine or S-1 as adjuvant chemotherapy for
      advanced pancreatic cancer. Using laser-captured microdissection and real-time RT
      PCR assay, we quantitatively evaluated the mRNA levels of 10 genes associated
      with patient prognosis and sensitivity to chemotherapy using paraffin-embedded
      specimens of the primary tumors resected before the start of adjuvant
      chemotherapy. In univariate analyses, a low gene expression level of gamma
      glutamyl hydrolase (GGH) and a high gene expression level of folylpolyglutamate
      synthase correlated with a favorable outcome. In a multivariate analysis, a low
      gene expression level of dihydropyrimidine dehydrogenase (DPD) and GGH
      significantly correlated with outcome (hazard ratio of the high DPD group to the
      low DPD group: 5.55; 95% confidence interval (CI) 1.27-24.05; P=0.022; the high
      GGH group to the low GGH group: 3.77; 95% CI 1.04-13.79, P=0.043). For adjuvant
      chemotherapy of patients with pancreatic cancer, the mRNA level of DPD and GGH
      may affect the prognosis of these patients.

PMID- 22977628
TI  - Expression of DBC1 is associated with nuclear grade and HER2 expression in breast
      cancer.
AB  - DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumor-suppressor gene
      cloned from breast cancer specimens and is reported to regulate p53-dependent
      apoptosis through its specific inhibition of SIRT1 deacetylase. Although SIRT1
      plays a pivotal role in carcinogenesis by regulating cellular proliferation,
      survival and death, its role in breast cancer remains controversial. Therefore,
      we aimed to investigate the expression status and clinicopathological
      significance of DBC1 and SIRT1 in breast cancer tissues. We evaluated the
      expression of DBC1 and SIRT1 in breast core-needle biopsy specimens from 48
      primary breast cancer patients between 2005 and 2008. These patients were treated
      with primary systemic chemotherapy and subsequent surgical resection of the
      lesions. Immunohistochemical expression scores of DBC1 and SIRT1 were evaluated,
      and the relationship between their expression levels and clinicopathological
      features of breast cancer was analyzed. The expression was observed exclusively
      in the nuclei of normal and neoplastic ductal cells. In breast biopsy specimens,
      positive expression of DBC1 and SIRT1 was noted in 85 and 98% of patients,
      respectively. Expression of DBC1 was significantly associated with the tumor
      nuclear grade (P=0.019). DBC1 and SIRT1 expression was inversely correlated with
      HER2 expression (P=0.026 and 0.003, respectively). Lower expression of DBC1 and
      SIRT1 indicated a tendency for a favorable pathological response to chemotherapy,
      although this was not statistically significant. Our results reveal that the
      expression of DBC1 and SIRT1 in breast tissues is associated with tumor
      characteristics.

PMID- 22977630
TI  - Expression and clinical significance of the DNA repair enzyme MYH in esophageal
      squamous cell carcinoma.
AB  - MYH is an important enzyme in combating DNA oxidative stress in the occurrence
      and development of various types of tumors. To investigate the correlation
      between expression of the DNA repair enzyme MYH in esophageal squamous cell
      carcinoma and 8-oxoguanine (8-oxoG) oxidative damage, as well as the clinical
      significance of altered MYH expression, tissues from 175 esophageal carcinoma
      cases were investigated in the present study. MYH expression and 8-oxoG oxidative
      damage in squamous cell carcinoma and adjacent normal tissue were assessed by
      immunohistochemistry and Western blotting. In 82.9% (145/175) of the cases, MYH
      protein expression in esophageal squamous cell carcinoma was lower than that of
      adjacent normal tissue (t=4.24, P<0.001). Additionally, 8-oxoG staining was
      higher in the tumors than in the normal tissue. Lower expression of MYH in
      esophageal squamous cell carcinoma was associated with depth of invasion, venous
      invasion, TNM stage and lymph node metastasis (P<0.05). In conclusion, a lower
      MYH expression level in esophageal cell carcinoma tissue was inversely associated
      with more severe 8-oxoG oxidative damage, suggesting that changes in MYH activity
      correspond to increased DNA damage in tumor cells. The use of MYH expression as a
      postoperative index for esophageal squamous cell carcinoma may guide the
      formulation of individualized chemotherapy for patients after surgery.

PMID- 22977629
TI  - Association between collagen type XI alpha1 gene polymorphisms and papillary
      thyroid cancer in a Korean population.
AB  - Collagen type XI alpha1 (COL11A1) gene overexpression has been implicated as a
      candidate marker of various types of cancers. In this study, we investigated
      whether coding region single nucleotide polymorphisms (cSNPs) of the COL11A1 gene
      are associated with papillary thyroid cancer (PTC) in a Korean population. Four
      cSNPs [rs12731843 (Lys276Asn), rs3753841 (Pro1335Leu), rs1763347 (Gly1516Gly) and
      rs2229783 (Ile1602Ile)] were genotyped using direct sequencing in 98 PTC patients
      and 366 control subjects. Logistic regression analysis for each cSNP revealed an
      association between rs1763347 and PTC in a dominant model [CT/TT vs. CC,
      p=0.0042, odds ratio (OR)=0.50, 95% confidential interval (CI) 0.31-0.81].
      Analysis of allelic frequency showed that the T alleles of rs1763347 and
      rs2229783 were significantly associated with reduced risk of PTC (p=0.010,
      OR=0.61, 95% CI 0.42-0.89 in rs1763347; p=0.007, OR=0.62, 95% CI 0.44-0.88 in
      rs2229783). Additionally, in the analysis of haplotype, the CC haplotype
      consisting of rs1763347 and rs2229783 was associated with PTC in codominant
      (p=0.011, OR=1.56, 95% CI 1.11-2.21) and recessive models (p=0.020, OR=1.70, 95%
      CI 1.09-2.66). The TT haplotype was also associated with PTC in a codominant
      model (p=0.006, OR=0.58, 95% CI 0.39-0.88). The frequency of the CC haplotype was
      higher in the PTC patients (0.71) compared to the control subjects (0.61),
      whereas the frequency of the TT haplotype was lower in the PTC patients (0.20 and
      0.30 in PTC patients and control subjects, respectively). The results suggest
      that the COL11A1 gene may be associated with PTC and, in particular, that the T
      allele of rs1763347 and rs2229783 may contribute to a reduced risk of PTC.

PMID- 22977631
TI  - Interleukin 7 receptor gene polymorphisms and haplotypes are associated with
      susceptibility to IgA nephropathy in Korean children.
AB  - An abnormal T-cell response is involved in the pathogenesis of various renal
      diseases. Survival of naive T cells is dependent on interleukin 7 (IL7) and its
      receptor (IL7R). Thus, we investigated the association between IL7R single
      nucleotide polymorphisms (SNPs) and childhood IgA nephropathy (IgAN). We analyzed
      the genotypic distributions of two missense SNPs of IL7R, rs1494558 (Ile66Thr)
      and rs1494555 (Val138Ile), among 198 pediatric IgAN patients and 288 healthy
      controls. Haplotype analysis and measurement of pair-wise linkage disequilibrium
      were performed. In addition, the genotypes of patient subgroups, determined by
      the presence of nephrotic range proteinuria (>40 mg/m(2)/h) and pathological
      advancement, were analyzed. The genotyping data of IgAN patients and controls
      showed significant differences in rs1494558 (codominant, P=0.0003; dominant,
      P=0.0003) and rs1494555 (codominant, P=0.0038; dominant, P=0.0099). In the
      haplotype analysis, AC (codominant, P=0.0066) and GT (codominant, P=0.0005;
      dominant, P=0.0006) were significantly associated with susceptibility to IgAN.
      Furthermore, in the analysis of clinical subgroups of IgAN patients, rs1494558
      was associated with nephrotic range proteinuria (codominant, P=0.027; recessive,
      P=0.023). Our results suggest that IL7R may be associated with disease
      susceptibility and proteinuria in childhood IgAN.

PMID- 22977632
TI  - Prognostic significance of microRNA gene polymorphisms in patients with
      surgically resected colorectal cancer.
AB  - MicroRNAs (miRNAs) are small 19- to 22-nucleotide sequences of RNA that
      participate in the regulation of cell differentiation, cell cycle progression and
      apoptosis. Although single-nucleotide polymorphisms (SNPs) in miRNA regions are
      considered unlikely to be functionally important, nucleotide variations within
      the sequences of primary (pri)- or precursor (pre)-miRNAs may affect miRNA
      processing and ultimately result in the modification of miRNA expression. The aim
      of this study was to investigate associations between four SNPs in pre-miRNA
      genes and the survival of colorectal cancer patients. A total of 407 colorectal
      patients were consecutively enrolled. DNA was extracted from blood specimens, and
      the hsa-mir-146aC>G, hsa-mir-149C>T, hsa-mir-196a2C>T and hsa-mir-499A>G
      polymorphisms were genotyped by PCR-RFLP. We were unable to identify independent
      prognostic SNPs for colorectal cancer. However, the heterozygous TC genotype of
      the 196a2C>T polymorphism was a significant risk factor for the overall survival
      of rectal cancer patients (HR=3.554, 95% CI 1.296-9.747, p=0.014). Further large
      population studies are warranted to define the 196a2C>T polymorphism as a
      prognostic factor of rectal cancer.

PMID- 22977633
TI  - Prognostic significance of urine neutrophil gelatinase-associated lipocalin in
      patients with septic acute kidney injury.
AB  - Acute kidney injury (AKI) is a common clinical problem which occurs in critically
      ill patients. Sepsis is now recognized as the most important contributing factor
      to AKI in this population. In clinical practice, certain studies have explored
      the urine neutrophil gelatinase-associated lipocalin (uNGAL) and the urine kidney
      injury molecule-1 (uKIM-1) as diagnostic and prognostic indices of AKI. Yet, it
      remains unclear whether uNGAL and uKIM-1 are associated with measures of disease
      severity and with adverse clinical outcomes in patients with established septic
      AKI of mixed cause and severity. Ninety-two septic patients with AKI were
      enrolled in a pilot study to test whether uKIM and uNGAL levels predict 180-day
      mortality. We initially performed univariate Cox proportional hazards analyses
      incorporating multiple demographic, clinical and laboratory variables. As a
      result, the APACHE II score (p= 0.014) and uNGAL (p= 0.015) were identified as
      independent predictors of 180-day mortality. On the other hand, there was no
      statistical difference in event-free survival between patients with and without
      higher serum creatinine, creatinine clearance and uKIM-1 (data not shown). In
      conclusion, uNGAL may be a promising predictor for septic patients with AKI,
      resulting in a clear increase in 180-day mortality. Further clinical evaluation
      of uNGAL is underway.

PMID- 22977634
TI  - Relationship of ovarian volume with mean platelet volume and lipid profile in
      patients with polycystic ovary syndrome.
AB  - The aim of the present study was to evaluate the relationship between ovarian
      volume (OV) and mean platelet volume (MPV) in women with polycystic ovary
      syndrome (PCOS). Hormonal parameters and lipid profile of cases, and their
      relationship to OV were also assessed. Bilateral OV of 210 newly diagnosed PCOS
      patients and 100 healthy non-hirsute women were measured by ultrasonography.
      Blood samples were obtained for full blood count, hormone levels and for lipid
      profiles. It was found that MPV increased gradually as OV increased. This implies
      a higher risk of hypercoagulability and therefore an increased risk of future
      cardiovascular disease.

PMID- 22977635
TI  - Association study between polymorphisms of CD28, CTLA4 and ICOS and non-segmental
      vitiligo in a Korean population.
AB  - CD28 molecule (CD28), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and
      inducible T-cell co-stimulator (ICOS) are important regulators of the immune
      system. Vitiligo, a common autoimmune skin disorder, is characterized by a loss
      of melanocytes that results in cutaneous white patches. The aim of the present
      study was to determine whether or not polymorphisms of the CD28, CTLA4 and ICOS
      genes are associated with non-segmental vitiligo in a Korean population. To
      determine the relationships between CD28, CTLA4 and ICOS genes and vitiligo, four
      single nucleotide polymorphisms (SNPs) associated with the CD28 gene [rs1879877
      (promoter, -1198), rs3181097 (promoter, -1059), rs2140148 (intron 1) and
      rs3116494 (intron 2)], two SNPs associated with the CTLA4 gene [rs231777 (intron
      1) and rs231779 (intron 1)] and five SNPs associated with the ICOS gene
      [rs4270326 (intron 3), rs11571314 (intron 3), rs10183087 (3' untranslated region;
      UTR), rs4404254 (3'UTR) and rs1559931 (3'UTR)] were selected. Two hundred and
      thirty-one patients with non-segmental vitiligo (NSV) and 405 healthy controls
      were enrolled. Genotyping was performed using the restriction fragment length
      polymorphism technique and direct sequencing. SNPStats, Haploview 4.2 and SPSS
      18.0 were used to conduct the analyses. Significant differences were noted
      between CTLA4 (p<0.05) and NSV, but not CD28 and ICOS (p>0.05). However, these
      associations disappeared after Bonferroni correction. The CD28, CTLA4 and ICOS
      genes may not be associated with NSV.

PMID- 22977636
TI  - Expression and function of ABCG2 in head and neck squamous cell carcinoma and
      cell lines.
AB  - Overexpression of breast cancer resistance protein, the ATP-binding cassette,
      subfamily G, member2 (BCRP/ABCG2), confers multidrug resistance to tumor cells
      and often limits the efficacy of chemotherapy. The aim of this study was to
      investigate the expression and functional activity of ABCG2 in head and neck
      squamous cell carcinoma (HNSCC) and corresponding cell lines.
      Immunohistochemistry was performed to investigate the presence of the ABCG2
      transporter in HNSCC tissues. Expression of ABCG2 in the Hep-2, Hep-2T, CNE and
      FaDu cell lines was analyzed by real-time quantitative reverse transcription
      polymerase chain reaction and Western blotting at the levels of messenger RNA
      (mRNA) and protein, respectively. The drug sensitivity of the above four cell
      lines to mitoxantrone was detected using MTT, and the drug accumulation of
      mitoxantrone was analyzed by flow cytometry. Positive expression of ABCG2 was
      detected in 52.04% of the laryngeal cancer samples from 98 patients, in 65% of
      the 40 hypopharyngeal cancer samples and in 58.82% of the 34 nasopharyngeal
      cancer samples. The level of expression was found to be correlated with tumor TNM
      stage (P<0.05) and lymph node metastasis (P<0.01). All four HNSCC cell lines
      expressed ABCG2 at the mRNA and protein levels. The levels of ABCG2 expression in
      the four cell lines were significantly correlated with the function and
      sensitivity to mitoxantrone. The addition of fumitremorgin C at a concentration
      of 5 MUM to mitoxantrone treatment caused a varied increase in mitoxantrone
      accumulation of 1.09-fold, 1.33-fold (P<0.01), 1.4-fold (P<0.01) and 1-fold in
      the Hep-2, Hep-2T, CNE and FaDu cells, respectively. Expression of ABCG2 varied
      among the different types of carcinoma tissues and each HNSCC cell line, and it
      induced multidrug resistance and separation of cancer stem cells attributing to
      its efflux pump function. Thus, ABCG2 expression may be an unfavorable prognostic
      factor for HNSCC. Due to the negligible expression and function of ABCG2, we
      suggest that the FaDu cell line is suitable to be a negative control in studies
      involving HNSCC. Taken together, ABCG2 is a promising universal biomarker of
      cancer stem cells and a target gene for HNSCC chemotherapy.

PMID- 22977637
TI  - Sulfotransferase 1A1 Arg(213)His polymorphism and prostate cancer risk.
AB  - Sulfotransferase 1A1 (SULT1A1) is a member of the sulfotransferase family that
      plays an important role in the biotransformation of numerous carcinogenic and
      mutagenic compounds through sulfation. A transition, G to A at position 638, in
      the SULT1A1 gene, results in the Arg(213)His change. This single nucleotide
      polymorphism reduces the activity and thermostability of the SULT1A1 enzyme. In
      the present study, the relationship between the SULT1A1 Arg(213)His polymorphism
      and prostate cancer was investigated using PCR-RFLP. No significant difference in
      genotype and allele distribution was noted between the prostate cancer and
      control populations (P=0.072; P=0.099, respectively). The risk of prostate cancer
      in individuals carrying the SULT1A1(*)2 allele (His(213) allele) was determined
      by combining the SULT1A1(*)1/SULT1A1(*)2 (Arg/His(213)) and
      SULT1A1(*)2/SULT1A1(*)2 (His/His(213)) genotypes. No association was observed
      between SULT1A1 Arg(213)His polymorphism and prostate cancer incidence (P=0.24;
      OR, 1.36; 95% CI, 0.84-2.25). However, the His(213) allele was found to increase
      the risk of prostate cancer by 1.36-fold. In smoker and non-smoker populations,
      no significant relationship was determined between the prostate cancer and
      control population (P=0.45; P=0.34, respectively).

PMID- 22977638
TI  - Novel sequence variants and common recurrent polymorphisms of BRCA2 in Sri Lankan
      breast cancer patients and a family with BRCA1 mutations.
AB  - We previously reported BRCA1 mutations and sequence variants in Sri Lankan breast
      cancer patients. Mutations and sequence variants of the BRCA2 gene were studied
      in 149 study participants from the same cohort. There were 55 familial and 54
      sporadic breast cancer patients, 20 at-risk individuals and 20 healthy controls.
      Direct sequencing (exon 11) and sequencing of abnormal bands after screening with
      single-strand conformation polymorphism (remaining exons) were used to detect
      mutations and sequence variants. Twenty-three sequence variants were found in the
      BRCA2 gene. Two novel pathogenic frame-shift additions resulting in a premature
      stop codon (c.2403 insA/exon 11, c.2667 insT/exon 11) were identified. Possibly
      pathogenic two novel missense mutations (c.1191 A>C/exon 10, c.5695 A>C/exon 11)
      one novel intronic variant (IVS15-21 insTT), four novel silent mutations (c.969
      C>T/exon 9, c.1353 C>T/exon 10, c.2766 A>C/exon 11 and c.7452 A>G/exon 14) and
      one novel missense mutation (c.971 C>G/exon 9) were observed. One previously
      reported possibly pathogenic intronic variant (IVS81 G>C) and several previously
      reported silent mutations, missense mutations, and one 5' UTR polymorphism were
      detected. Pathogenic and possibly pathogenic mutations were more frequent in the
      BRCA2 gene among Sri Lankan familial breast cancer patients when compared to our
      previous findings for the BRCA1 gene.

PMID- 22977639
TI  - Octreotide enhances the sensitivity of the SKOV3/DDP ovarian cancer cell line to
      cisplatin chemotherapy in vitro.
AB  - The present study aimed to investigate the effects of octreotide (OCT) on the
      reversal of resistance of cisplatin-resistant cancer cells and on enhancement of
      the cisplatin sensitivity of cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2-5
      diphenyltetrazolium bromide method and flow cytometry were used to investigate
      the effect of cisplatin, OCT or the combination of these two compounds on the
      proliferation and apoptosis of SKOV3/DDP cells. Real-time, quantitative RT-PCR
      was used to detect the mRNA expression of SSTR2, MDR1, MRP2, GST-pi and EGFR in
      SKOV3/DDP cells following OCT treatment. At the concentration of 2.5-20 MUg/ml,
      OCT significantly reduced the IC(50) value (P<0.05) and promoted apoptosis
      (P<0.05) in the SKOV3/DDP cells in response to cisplatin. The synergistic effect
      of OCT and cisplatin on SKOV3/DDP cell proliferation was observed. SSTR2 was
      expressed on the SKOV3/DDP cell surface. OCT increased GST-pi expression (P<0.05)
      and reduced MRP2 and EGFR expression (P<0.05) in a dose-dependent manner.
      However, it had no effect on the expression of MDR1 (P>0.05). It is suggested
      that OCT inhibits ovarian cancer proliferation and promotes apoptosis, via the
      cell surface expression of SSRT2, and reverses cisplatin resistance through the
      inhibition of MRP2 and EGFR expression.

PMID- 22977640
TI  - Changes in serum thymidine kinase 1 levels during chemotherapy correlate with
      objective response in patients with advanced gastric cancer.
AB  - Serum thymidine kinase 1 (STK1) is a reliable proliferation marker in most solid
      tumors, including gastric cancer. The aim of this study was to evaluate whether
      STK1 levels are related to the tumor response to chemotherapy and survival in
      advanced gastric cancer. The results showed that the average STK1 level in
      patients with gastric cancer (5.57+/-3.07 pM) was significantly higher than that
      in the healthy controls (1.12+/-0.57) (P<0.001). Among the 84 patients, the
      average STK1 level (6.02+/-3.12) in the 56 patients who did not undergo surgery
      was higher than the level (4.68+/-2.78) in the 28 patients who received surgery
      (P=0.049). The STK1 value correlated with clinical stage, ECOG PS and serum CEA
      levels (P<0.001, P=0.001 and P=0.004, respectively), but not with age and gender.
      The average STK1 levels after 1,2 and 4 cycles of chemotherapy did not
      significantly decrease in the total patients, when compared to the levels prior
      to chemotherapy. Yet, after 2 cycles of chemotherapy, the average level of STK1
      was significantly decreased in patients who achieved an objective response (OR)
      (CR, PR or no recurrence). Particularly after 1 cycle of chemotherapy, the
      average level of STK1 in patients who achieved OR started to decline, while in
      most of the patients with disease progression or recurrence, the STK1 level
      started to increase. In patients receiving palliative chemotherapy or receiving
      adjuvant chemotherapy, a significant difference in the median PFS (median PFS,
      not defined vs. 4 months, P<0.001) or RFS (median RFS, not defined vs. 5 months,
      P<0.001) was noted between patients with decreased STK1 levels and patients with
      increased STK1 levels during the first 2 months of chemotherapy. The log-rank
      test showed that patients with decreased STK1 levels had a trend of a longer OS
      in the palliative chemotherapy group. Our results suggest that serum TK1 levels
      correlate with clinical stage, ECOG PS and serum CEA levels in patients with
      gastric cancer, and changes in STK1 levels during the first 2 months of
      chemotherapy may be more important for evaluating chemotherapy response,
      predicting PFS and RFS than baseline values of STK1 in patients with advanced
      gastric cancer.

PMID- 22977641
TI  - Microdissection of guinea pig extraocular muscles.
AB  - The guinea pig, a widely used experimental animal, has been used in myopia
      research in recent years. The structure of the extraocular muscles is important
      in research on eyeball movement, regulation of movement, binocular vision and
      surgical intervention. In this study, the anatomy and the structure of the
      extraocular muscles of guinea pigs were investigated. Five guinea pig eyes were
      dissected under a surgical microscope immediately after sacrifice, and an
      additional five were fixed in 10% formaldehyde solution and dissected under a
      surgical microscope 1 week after sacrifice. The guinea pig eye has seven
      extraocular muscles: two medial rectus muscles, one superior rectus muscle, one
      inferior rectus muscle, one superior oblique muscle and one inferior oblique
      muscle. The retractor bulbi muscle fibers surround the optic nerve longitudinally
      and insert circumferentially into the posterior pole of the eyeball. The lateral
      rectus was not found. Our results showed that there is a disparity between the
      structure of guinea pig extraocular muscles and that of humans.

PMID- 22977642
TI  - Human epidermal growth factor receptor 2 protein expression between primary
      breast cancer and paired asynchronous local-regional recurrences.
AB  - Knowledge concerning concordance of epidermal growth factor receptor 2 (HER2)
      expression between primary breast cancers and asynchronous local-regional
      recurrences is sparse. Receptor characteristics could be altered with time and
      may be affected by anticancer treatment. It remains uncertain whether recurrences
      have the identical or similar HER2 receptor expression pattern as the primary
      breast cancer. The aim of the present study was to evaluate whether HER2 is
      stable during the process of recurrence. Expression of HER2 was investigated
      immunohistochemically in paired samples of primary breast cancers and
      corresponding asynchronous local-regional recurrences (n=35). HER2 expression was
      scored as 0, 1+, 2+ or 3+. HER2 overexpression (2+ or 3+) was found in 48.57%
      (17/35) of the primary breast cancers and 45.71% (16/35) of the corresponding
      local-regional recurrences. A concordance of HER2 overexpression between the
      primary lesions and matching regional recurrences was observed in 85.71% of the
      breast cancer cases. Five out of the 35 paired samples (14.28%) were discordant.
      Only 3 patients who had 2+ HER2 expression in the primary tumors showed HER2 down
      regulation (0 or 1+) in the recurrences, while the HER2 score in 2 patients
      changed oppositely. Moreover, all of the cases with 3+ HER2 staining in the
      primary lesions retained HER2 overexpression in the recurrences. The HER2 is
      commonly expressed in breast cancer, and its expression in the primary tumors and
      the corresponding recurrences was concordant in the majority of the cases. As the
      receptor expression may lose or gain in recurrences at a probability of
      approximately 10%, assessment of the receptor status in recurrences is still
      encouraged.

PMID- 22977643
TI  - Association between the hMSH2 IVS12-6 T>C polymorphism and cancer risk: A meta
      analysis.
AB  - The hMSH2 gene, a member of the mismatch repair (MMR) pathway, plays a key role
      in the maintenance of genomic integrity. The common sequence variation in hMSH2,
      IVS12-6 T>C, has been implicated in cancer risk. However, the results of
      published studies on this polymorphism remain conflicting. Hence, we conducted a
      meta-analysis to clarify the role of the hMSH2 IVS12-6 T>C polymorphism in
      cancer. We performed a comprehensive literature search updated to March 2011 of
      studies on the associations between the hMSH2 IVS12-6 T>C polymorphism and cancer
      risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess
      the strength of the associations. Thirteen studies involving 7,527 patients and
      8,762 control subjects were included in this meta-analysis. The overall results
      indicated no major influence of the polymorphism on cancer risk. However,
      stratified analysis by cancer types showed that the hMSH2 IVS12-6 polymorphism
      increased the risk for non-Hodgkin's lymphomas (heterozygote comparison: OR=1.62;
      95% CI 1.06-2.47). When stratified by the source of controls, significant
      associations were observed in hospital-based populations (heterozygote
      comparison: OR=1.28; 95% CI 1.02-1.61). These results indicate that the
      polymorphism of hMSH2, IVS12-6, may cause a different effect in different types
      of cancers. To draw more comprehensive conclusions, further prospective studies
      with larger numbers of participants worldwide are required to examine the
      associations between this polymorphism and cancer risk.

PMID- 22977644
TI  - Growth-dependent release of carbohydrate metabolism-related and antioxidant
      enzymes from Staphylococcus aureus strain 6 as determined by proteomic analysis.
AB  - Proteins released into the culture medium by Staphylococcus aureus (S. aureus)
      strain 6 were determined at the end of the exponential growth phase (4.5 h).
      Eleven proteins were identified by liquid chromatography coupled with mass
      spectrometry. Three proteins were predicted to have signal peptides indicating
      their extracellular localization. The other proteins were presumably located in
      the cytoplasm of the bacteria. Five out of the 11 proteins were involved in
      carbohydrate metabolism. Other intracellular proteins of S. aureus were not
      detected in the culture medium. This indicates that the release of these 11
      proteins was specific and that unspecific protein release due to damaged or dying
      bacteria did not play a role. It is suggested that enzymes associated with
      carbohydrate metabolism may provide the energy necessary for the transition of
      bacteria from a resting to a proliferative state. Another enzyme released by S.
      aureus, superoxide dismutase, may catalyze redox reactions in this context. The
      production of other proteolytic enzymes and toxins may take place at later stages
      of bacterial growth. A cocktail of these 11 proteins was used for the
      immunization of mice. Indeed, vaccination with these proteins prolonged the
      survival times of mice upon infection with S. aureus strain 6. Therefore, these
      proteins may have implications for the development of novel strategies for the
      prevention and therapy of S. aureus infections.

PMID- 22977645
TI  - Diagnostic value of interleukin 22 and carcinoembryonic antigen in tuberculous
      and malignant pleural effusions.
AB  - The aim of this study was to investigate the diagnostic value of interleukin 22
      (IL-22) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions
      (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 56
      patients were classified on the basis of diagnosis as TPE (n=28) and MPE (n=28).
      The concentration of IL-22 was determined by ELISA. Lactate dehydrogenase (LDH),
      adenosine dehydrogenase (ADA) and CEA levels were also determined in all
      patients. A significant difference was observed in the levels of ADA and CEA
      (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The
      concentration of IL-22 in TPE was significantly higher compared to MPE (P<0.01).
      With a threshold value of 49 pg/ml, IL-22 had a sensitivity of 82.14% (23/28) and
      a specificity of 96.43% (27/28) for differential diagnosis. The combined
      detection of IL-22 and CEA had a sensitivity of 100% (28/28) and a specificity of
      96.43% (27/28) to distinguish TPE from MPE. TPEs showed significantly higher
      levels of IL-22 compared to MPEs. The combined detection of IL-22 and CEA may be
      more valuable in the differential diagnosis between TPE and MPE.

PMID- 22977646
TI  - Microsurgical anatomical study of the frontotemporal-zygomatic arch approach to
      the superior petroclival region.
AB  - The aim of this study was to explore the microsurgical anatomy of the superior
      petroclival region, and thus provide an anatomical basis for operative
      approaches. The frontotemporal-orbitozygomatic approach was performed on 20 sides
      of 10 adult cadaver heads. In comparison to the range of the exposure with the
      removal of the anterior clinoid process, posterior clinoid process and part of
      the tip of the petrous bone, we measured the neurovascular course and their
      relation to the superior petroclival region. We found that the trochlear nerve
      goes through the edge of the tentorial marginal branch, taking 5.42 mm (4.26
      6.96) away from the ophthalmic nerve. Exposing the arteria basilaris, above the
      middle piece the length of exposure is 15.52 mm (14.22-16.70), resulting in the
      posterior cerebral artery and the front part of the midbrain being completely
      exposed. There is little exposure on the front part of the pons and midbrain with
      a length of 5.6 mm (4.38-6.82). Removing the partial petrosal bones, the inferior
      segment of the basal artery is exposed, while 4 other nerves cab also be
      observed: Cranial, abducens, facial and vestibulocochlear. The frontotemporal
      zygomatic arch approach can clearly expose the superior petroclival region.
      Obtaining more information on the relationship between the location of these
      structures, is therefore helpful in improving the safety and success of surgery
      in this region.

PMID- 22977647
TI  - Comparison between different thickness umbrella-shaped expandable radiofrequency
      electrodes (SuperSlim and CoAccess): Experimental and clinical study.
AB  - The purpose of the present study was to compare the size and configuration of the
      ablation zones created by SuperSlim and CoAccess electrodes, using various
      ablation algorithms in ex vivo bovine liver and in clinical cases. In the
      experimental study, we ablated explanted bovine liver using 2 types of electrodes
      and 4 ablation algorithms (combinations of incremental power supply, stepwise
      expansion and additional low-power ablation) and evaluated the ablation area and
      time. In the clinical study, we compared the ablation volume and the shape of the
      ablation zone between both electrodes in 23 hepatocellular carcinoma (HCC) cases
      with the best algorithm (incremental power supply, stepwise expansion and
      additional low-power ablation) as derived from the experimental study. In the
      experimental study, the ablation area and time by the CoAccess electrode were
      significantly greater compared to those by the SuperSlim electrode for the single
      step (algorithm 1, p=0.0209 and 0.0325, respectively) and stepwise expansion
      algorithms (algorithm 2, p=0.0002 and <0.0001, respectively; algorithm 3, p=
      0.006 and 0.0407, respectively). However, differences were not significant for
      the additional low-power ablation algorithm. In the clinical study, the ablation
      volume and time in the CoAccess group were significantly larger and longer,
      respectively, compared to those in the SuperSlim group (p=0.0242 and 0.009,
      respectively). Round ablation zones were acquired in 91.7% of the CoAccess group,
      while irregular ablation zones were obtained in 45.5% of the SuperSlim group
      (p=0.0428). In conclusion, the CoAccess electrode achieves larger and more
      uniform ablation zones compared with the SuperSlim electrode, though it requires
      longer ablation times in experimental and clinical studies.

PMID- 22977649
TI  - Unusual bacterial infections and the pleura.
AB  - Rickettsiosis, Q fever, tularemia, and anthrax are all bacterial diseases that
      can affect the pleura. Rocky Mountain Spotted Fever (RMSF) and Mediterranean
      Spotted Fever (MSF) are caused by Rickettsia rickettsii and Rickettsia conorii,
      respectively. Pleural fluid from a patient with MSF had a neutrophil-predominant
      exudate. Coxiellaburnetii is the causative agent of Q fever. Of the two cases
      described in the literature, one was an exudate with a marked eosinophilia while
      the other case was a transudate due to a constrictive pericarditis. Francisella
      tularensis is the causative agent of tularemia. Pleural fluid from three
      tularemia patients showed a lymphocyte predominant exudate. Bacillusanthracis is
      the causative agent of anthrax. Cases of inhalational anthrax from a recent
      bioterrorist attack evidenced the presence of a serosanguineous exudative pleural
      effusion. These four bacterial microorganisms should be suspected in patients
      presenting with a clinical history, exposure to known risk factors and an
      unexplained pleural effusion.

PMID- 22977650
TI  - Evaluation of the efficacy and safety of percutaneous biopsy of lung.
AB  - INTRODUCTION: Percutanous needle biopsy of the lung (PNBL), under image guidance,
      has established itself as a safe and effective minimally-invasive method of
      obtaining a tissue diagnosis of pulmonary lesions, for selected patients with
      suspected pathologic processes. The purpose of this study was to evaluate the
      diagnostic yield and safety of percutaneous core biopsy of the lung (PCBL)
      without Fine Needle Aspiration Biopsy (FNAB), with specific attention to
      potential risk factors that may predict post-biopsy pneumothorax. MATERIALS AND
      METHODS: A retrospective analysis of 75 consecutive PCBL procedures between
      January 2006 to March 2008 involving 72 patients with a documented pulmonary
      nodule or mass lesion on CT scan of Thorax. The study population included 38
      males (52.8%) and 34 females (47.2%) aged 20-85 years (mean age 63.6 years). A co
      axial cutting system with a 19-gauge outer needle and a 20-gauge inner automated
      cutting needle (Temno, Allegiance Healthcare Corporation, Ohio, USA) was used in
      all patients. RESULTS: Lesions varied in size from 0.7cm to 10.7cm (mean maximum
      trans-axial diameter 3.1cm). The mean number of core biopsy samples obtained was
      3.1 (range 1-5). Of the 75 PCBL procedures, 71 yielded specimens adequate for
      histopathologic evaluation, consistent with a technical success rate of 95%.
      Malignancy was detected in 48 specimens (64%) and benign diagnoses were
      identified in 23 specimens (31%). As mentioned, 4 specimens (5%) were
      nondiagnostic. The most common biopsy-induced complication was pneumothorax,
      occurring in 15 patients (20%), with 4 (5.3%) requiring thoracostomy tube
      placement. CONCLUSION: PCBL without FNAB, under CT fluoroscopy guidance, has an
      excellent diagnostic accuracy in obtaining a conclusive histologic diagnosis of
      thoracic lesions and is comparable to FNAB in terms of safety and rates of
      occurence of complications.

PMID- 22977651
TI  - Critique and appraisal of a study on the attitudes towards organ donor advocacy
      scale.

PMID- 22977652
TI  - Development and Psychometric Evaluation of the Instrument: Attitudes Towards
      Organ Donor Advocacy Scale (ATODAS).

PMID- 22977648
TI  - The role of hyperosmotic stress in inflammation and disease.
AB  - Hyperosmotic stress is an often overlooked process that potentially contributes
      to a number of human diseases. Whereas renal hyperosmolarity is a well-studied
      phenomenon, recent research provides evidence that many non-renal tissues
      routinely experience hyperosmotic stress that may contribute significantly to
      disease initiation and progression. Moreover, a growing body of evidence
      implicates hyperosmotic stress as a potent inflammatory stimulus by triggering
      proinflammatory cytokine release and inflammation. Under physiological
      conditions, the urine concentrating mechanism within the inner medullary region
      of the mammalian kidney exposes cells to high extracellular osmolarity. As such,
      renal cells have developed many adaptive strategies to compensate for increased
      osmolarity. Hyperosmotic stress is linked to many maladies, including acute and
      chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity
      triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial
      depolarization, DNA damage, and cell cycle arrest, thus rendering cells
      susceptible to apoptosis. However, many adaptive mechanisms exist to counter the
      deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement
      and up-regulation of antioxidant enzymes, transporters, and heat shock proteins.
      Osmolyte synthesis is also up-regulated and many of these compounds have been
      shown to reduce inflammation. The cytoprotective mechanisms and associated
      regulatory pathways that accompany the renal response to hyperosmolarity are
      found in many non-renal tissues, suggesting cells are commonly confronted with
      hyperosmotic conditions. Osmoadaptation allows cells to survive and function
      under potentially cytotoxic conditions. This review covers the pathological
      consequences of hyperosmotic stress in relation to disease and emphasizes the
      importance of considering hyperosmolarity in inflammation and disease
      progression.

PMID- 22977653
TI  - Common Symptoms and Distress Experienced Among Patients with Colorectal Cancer: A
      Qualitative part of Mixed Method Design.
AB  - BACKGROUND: Colorectal cancer is one of the most common types of tumour in the
      world. Treatment side effects, together with the tumour symptoms, can result in a
      'symptom burden'. To understand the patient's burden during chemotherapy
      treatment and plan effective symptom relief there is a need for more knowledge
      about the experience of symptoms from the patients' perspective. OBJECTIVES: The
      study was designed to qualitatively identify and describe the most common
      symptoms among patients treated for colorectal cancer, and discover whether there
      are barriers to reporting symptoms. METHODS: Thirteen Swedish patients diagnosed
      with colorectal cancer and treated with chemotherapy were interviewed face-to
      face. The interviews were audio-taped and transcribed verbatim. The transcripts
      were analysed by following the principles of qualitative content analysis.
      RESULTS: Nine symptoms/forms of distress were identified. Those most frequently
      expressed were fatigue, changed bowel habits, and affected mental well-being,
      closely followed by nausea, loss of appetite and neurological problems. Of
      particular note were the affected mental well-being, the magnitude of the
      neurological problems described, the symptoms related to skin and mucous membrane
      problems, and the reports of distressing pain. Barriers to symptom control were
      only expressed by the patients in passing and very vaguely. CONCLUSION: This
      study confirms other reports on most common symptoms in colorectal cancer. It
      also highlights the early onset of symptoms and provides data on less well
      studied issues that warrant further study, namely affected mental well-being, the
      magnitude of the neurological problems and symptoms related to the skin and
      mucous membranes. Nurses need to be sensitive to the patients' need presented and
      not only noting symptoms/distresses they have guidelines for.

PMID- 22977655
TI  - Differences in health and illness beliefs in zimbabwean men and women with
      diabetes.
AB  - This study explored beliefs about health and illness that might affect self-care
      and health-seeking behaviours in Zimbabwean men and women with diabetes. Gender
      differences were indicated in a previous study but their extent has not been
      studied. The present study used a qualitative descriptive design with semi
      structured interviews to gain a deeper understanding of the phenomena. The sample
      consisted of 21 participants, 11 females aged 19-61 years (Median 44 years) and
      10 males aged 22-65 years (Median 52 years). Qualitative content analysis was
      used. Health was described as freedom from diseases and enjoying well-being. Both
      males and females displayed limited knowledge about diabetes and dissimilarities
      in health-seeking behaviours. Women, in contrast to men, were more active in self
      care and used various measures besides drugs as they related to a higher extent
      the cause of diabetes to supernatural factors like gods and witches. They sought
      information from self-help groups and help from outside the professional health
      sector like healers in the folk sector. Prolonged economic disruption also had
      negative effects towards maintenance of healthy life-styles as both men and women
      struggled to get money for food and drugs. Thus, the study highlighted that
      knowledge about diabetes and its management are important for self-care. There is
      therefore need to develop acceptable and affordable gender- sensitive diabetes
      care programmes that enhance patient participation, empowerment and promotion of
      health.

PMID- 22977654
TI  - Meanings of being critically ill in a sound-intensive ICU patient room - a
      phenomenological hermeneutical study.
AB  - The aim of this study was to illuminate the meanings of being critically ill in a
      sound-intensive ICU patient room, as disclosed through patients' narratives.
      Patient rooms in ICUs are filled with loud activity and studies have revealed
      sound levels comparable to those of a busy road above the patient's head. There
      is a risk that the sound or noise is disturbing and at worst a major problem for
      the patient, but there is a lack of knowledge concerning the patients' own
      experiences. Thirteen patients were asked to narrate their experiences of the
      sound environment in ICU patient rooms. The interviews were analyzed using a
      phenomenological- hermeneutical method inspired by the philosophy of Ricoeur. Six
      themes emerged from the analysis. CONCLUSION: The meanings of being a patient in
      a sound- intensive environment were interpreted as never knowing what to expect
      next regarding noise, but also of being situated in the middle of an
      uncontrollable barrage of noise, unable to take cover or disappear. This
      condition is not to be seen as static; for some patients there is movement and
      change over time. The meanings indicate that the unpredictable shifts between
      silence and disturbing sounds stress the critically ill patient and impede sleep
      and recovery. Our findings indicate the need to reduce disturbing and unexpected
      sounds and noise around critically ill patients in high-tech environments in
      order to facilitate wellbeing, sleep and recovery. Nurses have a vital role in
      developing such an environment.

PMID- 22977656
TI  - Molecular mechanisms of lymphatic metastasis in solid tumors of the
      gastrointestinal tract.
AB  - Tumor cell dissemination from the primary tumor site to distant organs is one of
      the characteristic properties of malignant tumors and represents a crucial step
      in the progression of disease. Although the pattern of spread may vary in
      different types of carcinomas, dissemination via the lymphatic system represents
      a common event in metastasis. The extent of lymph node metastasis is one of the
      major determinants for the prognosis of patients with gastrointestinal carcinomas
      and guides the therapeutically management. During the last decades, significant
      attention has been given to the molecular mechanisms that control lymphatic
      metastasis. The process of lymphangiogenesis has come into the focus.
      Lymphangiogenesis, the formation of newly lymphatics, comprises a series of
      complex cellular events and is controlled by a balance between pro- and anti
      lymphangiogenic signals. This article will briefly describe the lymphatic system
      and then provide an overview of the molecular players involved in tumor
      lymphangiogenesis.

PMID- 22977657
TI  - The secret of FOXP3 downregulation in the inflammation condition.

PMID- 22977658
TI  - Synergy between IL-6 and TGF-beta signaling promotes FOXP3 degradation.
AB  - The forkhead family transcription factor FOXP3 is critical for the
      differentiation and function of CD4(+) CD25(+) regulatory T cells (Treg). How
      FOXP3 protein level is negatively regulated under the inflammatory
      microenvironment is largely unknown. Here we report that the combination of
      transforming growth factor-beta (TGF-beta) and IL-6 treatment (IL-6/TGF-beta) can
      synergistically downregulate FOXP3 at the posttranslational level by promoting
      FOXP3 protein degradation. In our FOXP3 overexpression model, we found that IL
      6/TGF-beta treatment upregulated IL-6R expression but did not affect the
      stability of FOXP3 mRNA. Moreover, we found that the proteasome inhibitor MG132
      could inhibit IL-6/TGF-beta-mediated downregulation of FOXP3 protein, which
      reveals a potential pathway for modulating Treg activity by preventing FOXP3
      degradation during inflammation.

PMID- 22977659
TI  - Sema3F downregulates p53 expression leading to axonal growth cone collapse in
      primary hippocampal neurons.
AB  - Hippocampal nerve growth is regulated by the coordinated action of numerous
      external stimuli, including positively acting neurotrophin-derived growth cues
      and restrictive semaphorin cues, however the underlying cellular mechanisms
      remain largely unclear. We examined the potential cellular mechanism of
      Semaphorin3F (Sema3F) in cultured primary hippocampal neurons. We show that
      Sema3F can down-regulate p53 expression in primary hippocampal neurons, thereby
      contributing to growth cone collapse. Sema3F suppressed p53-induced pathways,
      which we show to be required to maintain growth cone structure. Sema3F-induced
      growth cone collapse was partially reversed by overexpression of p53, which
      promoted growth cone extension. Inhibition of p53 function by inhibitor, siRNAs,
      induced axonal growth cone collapse, whereas p53 over-expression led to larger
      growth cones in cultured primary hippocampal neurons.These data reveal a novel
      mechanism by which Sema3F can induce hippocampal neuron growth cone collapse and
      provide evidence for an intracellular mechanism for cross talk between positive
      and negative axon growth cues.

PMID- 22977660
TI  - Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell
      carcinoma.
AB  - Ovarian endometriosis has been associated with increased risk for ovarian clear
      cell carcinoma (CCC). Atypical endometriosis shares common molecular alterations
      with CCC and therefore, has been proposed as a precursor lesion of CCC, although
      it is unclear if benign endometriosis is pre-neoplastic. In this study, we
      examined some molecular alterations in ovarian benign endometriosis, atypical
      endometriosis, and CCC in comparison to papillary serous carcinoma (PSC). These
      included BAF250a (encoded by ARID1A), a recently identified major tumor
      suppressor in ovarian CCC, as well as hepatocyte nuclear factor (HNF)-1b,
      estrogen receptor (ER), progesterone receptor (PR), and P53. We confirmed that
      CCC but not PSC had loss of BAF250a expression, HNF-1b up-regulation, loss of ER
      expression and P53 expression. We further showed that both atypical endometriosis
      and adjacent CCC had loss of BAF250a expression (38.5% vs. 57.7%), HNF-1b up
      regulation (53.8% vs. 92.3%), and loss of ER (84.6% vs. 92.3%) and PR (76.9% vs.
      84.6%) expression. Importantly, about 20% of benign ovarian endometriosis had
      loss of BAF250a expression, 33% with HNF-1b up-regulation, 23% loss of ER
      expression and 50% loss of PR expression, respectively. The concurrent rate of
      loss of BAF250a expression, HNF-1b up-regulation, and loss of ER expression was
      not observed in any benign endometriosis, and was increased to 23.1% in atypical
      endometriosis, and was further increased to 42.3% in CCC. Therefore, the
      molecular alterations accumulate in a stepwise manner along the transformation
      process from benign endometriosis through atypical endometriosis to CCC. These
      data suggest that a portion of benign ovarian endometriosis has already undergone
      genetic alterations that lead to aberrant protein expression, possibly conferring
      a higher risk for malignant transformation.

PMID- 22977661
TI  - Effects of glutamine treatment on myocardial damage and cardiac function in rats
      after severe burn injury.
AB  - Treatment with glutamine has been shown to reduce myocardial damage associated
      with ischemia/reperfusion injury. However, the cardioprotective effect of
      glutamine specifically after burn injury remains unclear. The present study
      explores the ability of glutamine to protect against myocardial damage in rats
      that have been severely burned. Seventy-two Wistar rats were randomly divided
      into three groups: normal controls (C), burned controls (B) and a glutamine
      treated group (G). Groups B and G were subjected to full thickness burns
      comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg*d)
      glutamine and group B was given the same dose of alanine via intragastric
      administration for 3 days. Levels of serum creatine kinase (CK), lactate
      dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were
      measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac
      function indices and histopathological changes were analyzed at 12, 24, 48 and 72
      post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood
      lactic acid increased significantly, while myocardial ATP and GSH contents
      decreased. Compared with group B, CK, LDH, and AST levels were lower and blood
      lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover,
      cardiac contractile function inhibition and myocardial histopathological damage
      were significantly reduced in group G compared to B. Taken together, these
      results show that glutamine supplementation protects myocardial structure and
      function after burn injury by improving energy metabolism and by promoted the
      synthesis of ATP and GSH in cardiac myocytes.

PMID- 22977663
TI  - High RSF-1 expression correlates with poor prognosis in patients with gastric
      adenocarcinoma.
AB  - AIM: To investigate the expression and prognostic significance of RSF-1 in
      gastric adenocarcinoma. METHODS: RSF-1 expression was analyzed using
      immunohistochemical staining on tissue samples from a consecutive series of 287
      gastric adenocarcinoma patients who underwent tumor resections between 2003 and
      2006.The relationship between RSF-1 expression, clinicopathological factors, and
      patient survival was investigated. RESULTS: Immunohistochemical staining
      indicated that RSF-1 is highly expressed in 52.6% of gastric adenocarcinomas. RSF
      1 expression levels were closely associated with tumor size, histological
      differentiation, tumor stage, and lymph node involvement. Kaplan-Meier survival
      analysis showed that high RSF-1 expression exhibited a significant correlation
      with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis
      revealed that RSF-1 expression is an independent prognostic parameter for the
      overall survival rate of gastric adenocarcinoma patients. CONCLUSION: Our data
      suggest that RSF-1 plays an important role in gastric adenocarcinoma progression
      and that high RSF-1 expression predicts an unfavorable prognosis in gastric
      adenocarcinoma patients.

PMID- 22977662
TI  - Expression of phosphorylated mTOR and its regulatory protein is related to
      biological behaviors of ameloblastoma.
AB  - The present study investigated the relationship between the expression of p-mTOR,
      p-4EBP1 and p-p70S6K in the cytoplasm and nucleus of ameloblastoma (AB) cells and
      the invasiveness of ABs. Immunohistochemistry was performed to detect the
      expression of p-mTOR, p-4EBP1 and p-p70S6K in ABs and the level of these proteins
      in the nucleus and cytoplasm was scored. There was ectopic expression of p-mTOR
      in ABs. 27 AB patients were positive for p-mTOR expression in the nucleus and 47
      for p-mTOR expression in the cytoplasm. The ectopic expression of p-4EBP-1 was
      also noted. 23 patients (27%) were positive for p-4EBP-1 expression in the
      nucleus and 55 (64.7%) for p-4EBP-1 expression in the cytoplasm. The ectopic
      expression of p-p70S6K was also noted. Of these patients, 33 were positive for p
      p70S6K expression in the nucleus (38.8%) and 45 for p-p70S6K expression in the
      cytoplasm (52.9%). Statistical analysis showed the expression of three proteins
      in the nucleus of patients with recurrent cancer was markedly higher than that in
      those with primary cancer. The expression of p-mTOR, p-4E-BP1 and p-p70S6K in the
      nucleus was related to the invasiveness of ABs. Multivariable analysis with Cox
      proportional hazards model showed the p-mTOR expression had influence on AB
      recurrence (OR: 6.417, 95%CI: 1.428-28.824). The possibility of AB recurrence in
      patients with nuclear p-mTOR expression was 6.417 folds higher than that in those
      with cytoplasmic p-mTOR expression. The nuclear expression of p-mTOR, p-4E-BP1
      and p-p70S6K was associated with biological behaviors (invasiveness) of ABs, and
      p-mTOR was an independent predictor of AB.

PMID- 22977664
TI  - Angiogenesis in upper tract urothelial carcinoma associated with Balkan endemic
      nephropathy.
AB  - Upper tract urothelial carcinoma (UTUC) associated with Balkan endemic
      nephropathy (BEN) is characterized by a number of aberrations in cell-cycle
      regulation and apoptosis. The aim of this study was to detect angiogenesis
      related marker(s) specific for BEN UTUC, and to examine the influence of HIF
      1alpha upon angiogenesis and apoptosis in UTUC. Present investigation included
      110 patients with UTUC, 50 from BEN region and 60 control tumors. Altered
      expression of VEGFR1 was more often present in control UTUC than in BEN tumors
      (p<0.005). It was associated with high grade, low and high stage, solid growth,
      and metaplastic change of control UTUC. Microvessel density assessed by CD31 (MVD
      CD31) was significantly higher in UTUC with lymphovascular invasion (p<0.05), and
      in BEN tumors with papillary growth (p<0.05). Discriminant analysis indicated
      that BEN and control tumors do not differ significantly in expression of
      angiogenesis related markers. The most important discriminant variable that
      determined control UTUC was expression of VEGFR1 (p=0.002). HIF 1alpha in UTUC
      significantly correlated with the low stage, papillary growth and expression of
      Bcl-2, Caspase-3 index, and MVD CD34 (p<0.001; 0.0005; 0.01; 0.005; 0.01,
      respectively). HIF-1alpha may be helpful marker in evaluation of UTUC, especially
      when combined with angiogenesis and apoptosis.

PMID- 22977665
TI  - Histopathological features predictive of a clinical diagnosis of ophthalmic
      granulomatosis with polyangiitis (GPA).
AB  - BACKGROUND: The limited form of Granulomatosis with Polyangiitis (GPA), formerly
      known as Wegener's Granulomatosis (WG) primarily involves the head and neck
      region, including the orbit, but is often a diagnostic challenge, particularly as
      it commonly lacks positive anti-neutrophil cytoplasm antibody (ANCA) titres or
      classical features on diagnostic orbital biopsies. The purpose of this study was
      to relate biopsy findings with clinical outcome and to determine which
      histopathological features are predictive of a clinical diagnosis of GPA.
      METHODS: Retrospective case series of 234 patients identified from the database
      of the UCL Institute of Ophthalmology Department of Eye Pathology as having had
      orbital biopsies of orbital inflammatory disorders performed between 1988 and
      2009. Clinical records were obtained for the patients and analysed to see whether
      patients had GPA or not, according to a standard set of diagnostic criteria
      (excluding any histopathological findings). Biopsy features were then correlated
      with the clinical diagnosis in univariate and multivariate analyses to determine
      factors predictive of GPA. RESULTS: Of the 234 patients, 36 were diagnosed with
      GPA and 198 with other orbital pathologies. The majority of biopsies were from
      orbital masses (47%). Histology showed a range of acute and chronic inflammatory
      pictures in all biopsies, but the presence of neutrophils (P<0.001), vasculitis
      (P<0.001), necrosis (P<0.001), eosinophils (P<0.02) and macrophages (P=0.05) were
      significantly associated with a later clinical diagnosis of GPA. In a
      multivariate analysis, only tissue neutrophils (OR=3.6, P=0.01) and vasculitis
      (OR=2.6, P=0.02) were independently associated with GPA, in contrast to previous
      reports associating eosinophils and necrosis with the diagnosis. CONCLUSIONS:
      Neutrophil, eosinophil and macrophage infiltration of orbital tissues, together
      with vasculitis and necrosis, are all associated with a clinical diagnosis of
      GPA, but only neutrophil infiltration and vasculitis are independently associated
      with this diagnosis. These features may assist in the establishing the diagnosis
      of limited GPA among patients with early orbital disease, particularly in the
      absence of positive serum ANCA titres.

PMID- 22977666
TI  - Non-invasive intraductal papillary neoplasms of the common bile duct: a
      clinicopathologic study of six cases.
AB  - Recently, several studies of intraductal papillary neoplasms (IPN) of the biliary
      tracts have been reported in the liver, but there have been only one study of
      them in the common bile duct (CBD). The author reviewed 34 archival pathologic
      materials of surgically resected specimens containing CBD tumors. RESULTS: Six
      cases (18%) of IPN of the CBD were found. All cases were non-invasive intraductal
      papillary carcinomas (IPC). The age of the patients with IPC ranged from 49 to 77
      years with a mean of 67 years. The male to female ratio was 4:2. The initial
      symptoms were abdominal pain in 2 cases, abdominal discomfort in 1 case, and
      obstructive jaundice in 3 cases. Imaging modalities including US, CT, MRI, and
      ERCP revealed the CBD luminal tumors and biliary dilations in all cases. Surgical
      procedures were pancreaticoduodenectomy in 4 cases and segmental resection in 2
      cases. The survival is relatively good; five patients are now alive, and one died
      of other disease. Grossly, all the 6 IPC showed intraductal papillary tumors. No
      mucus was found. Histologically, papillary proliferation of atypical cells with
      hyperchromatic nuclei regarded as malignant was recognized. The papillary
      proliferation was accompanied by fine fibrovascular cores in all cases. No
      stromal invasion was recognized, but lateral non-papillary in situ extension was
      recognized in 5 cases. Tubular formations were present in some areas in all
      cases. Goblet cells were present in 5 cases. No mucous hypersecretion was
      recognized. In one case, the tumor was composed of malignant oncocytes, and was
      regarded as intraductal oncocytic papillary carcinoma. Immunohistochemically, p53
      expression was present in 5 cases, and Ki-67 labeling ranged from 30% to 70%. The
      author presented clinicopathologic findings of 6 cases of non-invasive IPC of the
      CBD.

PMID- 22977667
TI  - Effect of GPE-AGT nanoparticle shRNA transfection system mediated RNAi on early
      atherosclerotic lesion.
AB  - OBJECTIVE: To investigate the effects of RNA interference targeting AGT on early
      atherosclerotic lesion in the hypertensive state. METHODS: Hypertension and
      atherosclerosis rats were treated with GPE nanoparticles carrying AGT shRNA.
      Systolic blood pressure and heart rate were measured for 2 consecutive weeks.
      Three days after treatment, the mRNA and protein expressions of AGT in the liver
      were measured by PCR and western blot assay, respectively. The blood levels of
      AGT and Ang II were determined by ELISA. H&E staining and electron microscopy
      were performed. RESULTS: Three days after AGT shRNA treatment, the mRNA and
      protein expressions of AGT in the liver were markedly reduced and the blood
      levels of AGT and Ang II dramatically decreased as compared to the remaining 3
      groups (P < 0.05). Three days after AGT shRNA treatment, the blood pressure was
      reduced by 27 +/- 4 mmHg when compared with that at baseline (P < 0.05). About 11
      days after AGT shRNA treatment, the blood pressure began to increase. The blood
      pressure remained unchanged in the remaining 3 groups. Microscopy showed the
      atherosclerotic lesions were markedly attenuated in AGT shRNA treated rats but
      the liver and kidney functions remained stable (P > 0.05) when compared with the
      remaining 3 groups. CONCLUSION: Transfection with GPE nanoparticle carrying AGT
      shRNA can stably lower the blood pressure and improve the atherosclerotic lesions
      which lead to the delayed development of early atherosclerotic lesions in
      hypertension rats with concomitant atherosclerosis.

PMID- 22977668
TI  - Papillary squamous cell carcinoma of the mandibular gingiva.
AB  - Papillary squamous cell carcinoma (PSCC) has rarely been reported in the oral
      cavity. Herein reported is a case of PSCC in the mandibular gum. A 70-year-old
      man consulted our hospital because of a papillary tumor in the left mandibular
      gum. Physical examination revealed an exophytic papillary tumor of the left
      mandibular gum, and an excision of the tumor was performed. Grossly, the tumor
      was exophytic and papillary, and measured 1 x 1 x 0.8 cm. Microscopically, the
      tumor showed exophytic papillary proliferation with fibrovascular cores and
      consisted of atypical squamous epithelial cells. The tumor cells showed
      hyperchromasia, nuclear atypia, mitotic figures, apoptotic bodies, cancer pearls,
      and individual keratinization. Mild stromal invasion was seen.
      Immunohistochemically, the tumor cells were positive for pancytokeratin AE1/3,
      pancytokeratin CAM5.2, p63, p53, and Ki-67 (labeling index=40%), but negative for
      human papilloma virus (HPV). HPV in situ hybridization revealed no signals.
      Therefore, PSCC was diagnosed. The lateral and vertical margins are negative for
      tumor cell. The pathological diagnosis was PSCC. The patient was healthy and free
      from tumor three months after the operation.

PMID- 22977669
TI  - Cerebral metastasis of cervical cancer, report of two cases and review of the
      literature.
AB  - Cervical cancers spread locally through the angiolymphatic apparatus and very
      rarely metastasize to the brain. The intracranial metastasis is a late event and
      a sign of poor prognosis. We present two cases of uterine cervical carcinomas
      with brain metastasis presenting with severe headaches in one case and
      hemiparesis and aphasia in the other one. Palliative craniotomy and debulking of
      the tumor was performed in both patients.

PMID- 22977670
TI  - Alveolar soft part sarcoma of the uterine corpus with pelvic lymph node
      metastasis: case report and literature review.
AB  - Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor, mainly
      localized in the extremities, occurring principally in adolescents and young
      adults. ASPS is uncommon in the female genital tract , and only 37 cases have
      been reported so far, including 9 cases in the uterine corpus and 17 cases in the
      uterine cervix. We here reported a case of ASPS occurring in the lower uterine
      segment . The case showed typical histological and immunohistochemical features.
      The patient had pelvic and para-aortic lymph node metastasis. To the best of our
      knowledge, it is the first such case described.

PMID- 22977672
TI  - LETTER TO THE EDITOR A New Application to Free-Nipple-Graft Reduction Mammaplasty
      for Breast and Nipple Projection.

PMID- 22977671
TI  - Juvenile xanthogranuloma developing after treatment of Langerhans cell
      histiocytosis: case report and literature review.
AB  - The synchronous or metachronous development of Langerhans cell histiocytosis and
      non-Langerhans cell histiocytosis in the same patient is rare. To date, only
      seven cases of xanthogranulomas developing in young patients with a history of
      Langerhans cell histiocytosis and systemic therapy have been reported in the
      literature. As of yet, the pathogenesis and the clinical significance of this
      phenomenon are unclear. We report the case of a 3 year old boy who developed
      juvenile Xanthogranulomas on the forehead and right upper eye lid 1.5 years after
      systemic therapy for monosystemic Langerhans cell histiocytosis of the bone and
      complete disease remission.

PMID- 22977673
TI  - LETTER TO THE EDITOR Reply to: Anatomical Landmarks for Safe Elevation of the
      Deep Inferior Epigastric Perforator Flap: A Cadaveric Study by Chowdhry et al.

PMID- 22977674
TI  - Cultural perspectives in facial allotransplantation.
AB  - Facial allotransplantation is a clinical reality, proposed to provide improved
      functional and aesthetic outcomes to conventional methods of facial
      reconstruction. Multidisciplinary efforts are needed in addressing not just the
      surgical and immunological issues but the psychological and sociological aspects
      as well. In view of this, an international survey was designed and conducted to
      demonstrate that attitudes toward facial allotransplantation are highly
      influenced by cultural background. Of all countries surveyed, France had the
      highest percentage of respondents willing to donate their faces (59%) and Iraq
      had the lowest (19%). A higher percentage of respondents were willing to
      accepting a face transplant (68%) than donate their face after death (41%).
      Countries with a dominant Western population show greater percentages of
      willingness to accept a face transplant, as they exhibit more positive variables,
      that is, (1) acceptance of plastic surgery for disfigurement and for cosmetic
      reasons and (2) awareness to the world's first face transplant. Countries with a
      dominant Western population also show greater percentages of willingness to
      donate their faces after death, as they exhibit more positive variables, that is,
      (1) positive attitude to organ donation by being an organ donor themselves, (2)
      acceptance of plastic surgery if disfigured, and (3) awareness to the world's
      first face transplant. Although religion was sometimes cited as a reason for not
      donating their faces, data analysis has shown religion not to be a strong
      associating factor to willingness to donate a face after death.

PMID- 22977675
TI  - A position statement on optimizing the role of oncoplastic breast surgery.
AB  - OBJECTIVES: To propose initiatives and actions that could improve access to and
      outcomes from oncoplastic breast surgery. METHODS: The author group met in May
      2010 to draft position statements on key unmet needs in oncoplastic breast
      surgery and how these may be addressed. At a second meeting in December 2010, the
      statements were voted upon and adjusted as necessary to achieve unanimous
      agreement. RESULTS: It was agreed that every patient undergoing breast cancer
      surgery should be assessed by an oncoplastic team capable of offering the full
      range of surgical options. However, currently, not all women are adequately
      informed about the surgical options available. Furthermore, levels of
      multidisciplinary working, standards of care, and levels of surgical training in
      the full range of breast oncoplastic techniques are suboptimal. Institution
      specific guidelines relating to the optimal patient pathway, the definition of
      clinical standards, and improved education in reconstructive surgery are
      required. Oncoplastic breast surgery should be offered to all patients, within
      the context of multidisciplinary teams that include accredited surgeons who
      consult with each other early in the treatment pathway. These teams should be
      focused on achieving not just positive oncologic outcomes, but also esthetic
      outcomes in line with patient wishes, to achieve optimal quality of life.
      CONCLUSIONS: There is a desire within the surgical community to improve patient
      outcomes by better incorporating oncoplastic procedures into the treatment
      pathways for breast cancer. These position statements represent the perspectives
      of a group of European plastic surgeons on the key elements required to achieve
      this goal.

PMID- 22977676
TI  - Indocyanine green near-infrared laser angiography predicts timing for the
      division of a forehead flap.
AB  - INTRODUCTION: Reconstruction with flaps requiring delayed division remains
      common, even with increasing use of free tissue transfer. Patient quality of life
      and function are significantly decreased during the delay period. Delay could be
      minimized by developing methods to reliably determine when the flap has developed
      sufficient vascular supply to undergo successful division. We report the use of
      laser angiography to determine the appropriate time for division of a forehead
      flap pedicle. METHODS: The patient who had risk factors for microvascular disease
      underwent near-infrared laser angiography using indocyanine green on
      postoperative day 21 to assess vascular perfusion of the flap. Although
      traditional clinical examination indicated the flap was not adequately perfused,
      laser angiography revealed perfusion to all areas of the flap, so the pedicle was
      divided. RESULTS: Pedicle division was successful, with no epidermolysis or
      necrosis. CONCLUSION: Near-infrared laser angiography with indocyanine green can
      assess perfusion status of the entire flap and inform the decision to divide the
      flap in an objective manner.

PMID- 22977677
TI  - CASE REPORT Removal of Exposed Titanium Reconstruction Plate After Mandibular
      Reconstruction With a Free Fibula Osteocutaneous Flap With Large Surgical Pin
      Cutters: A Case Report and Literature Review.
AB  - Locking reconstruction plates have led to significant improvement in
      osteosynthesis and graft anchorage in mandibular reconstruction following the
      free fibula osteocutaneous flap. Plate extrusion is the most common complication
      associated with mandibular reconstruction, occurring in approximately 20% to 48%
      of cases; often necessitating plate removal once the bone flap has united to the
      mandible. Radiation therapy is a known risk factor to the development of such a
      complication and it presents further challenges to the successful removal of the
      reconstruction plate. Several reports have been published regarding plate removal
      in the setting of orthopedics that describe the management of jammed or stripped
      locking screws, but few in the setting of mandibular reconstruction. In this
      case, we report the successful removal of an exposed titanium mandibular
      reconstruction plate from a 41-year-old woman 12 months after her initial
      reconstruction with a free fibula osteocutaneous flap and radiation therapy. The
      approach was selected because the chin and neck skin could not be expected to be
      raised for full plate exposure secondary to radiation-induced skin changes
      (thinning and friability). We also discuss the use of previously employed methods
      of plate removal in various settings as well as their inherent strengths and
      weaknesses.

PMID- 22977678
TI  - CASE REPORT Simultaneous Latissimus Dorsi Myocutaneous Flap Transfer and Revision
      Total Knee Arthroplasty With Allograft Extensor Mechanism Reconstruction: A Case
      Report.
AB  - INTRODUCTION: We present the case of a patient undergoing simultaneous
      reconstruction of a massive soft tissue deficit of the right knee along with
      total knee arthroplasty and allograft reconstruction of the extensor mechanism
      after multiple failed attempts to repair and revise the affected joint. METHODS:
      A latissimus dorsi myocutaneous flap was transferred to fill the soft-tissue
      deficit of the right knee. During the same procedure, a previously placed
      antibiotic-cement spacer was removed and a new total knee prosthesis was
      implanted. What remained of the damaged extensor mechanism was excised and
      replaced with a cadaveric allograft. RESULTS: The latissimus dorsi flap provided
      the necessary soft-tissue coverage of the revision. The new knee components and
      allograft extensor mechanism were satisfactorily implanted. One year after
      simultaneous reconstruction, the knee remains functional and free of infection.
      DISCUSSION: Although current literature may have indicated conversion to
      arthrodesis or prophylactic soft-tissue repair prior to revision, simultaneous
      soft-tissue and extensor mechanism repair along with revision total knee
      arthroplasty have yielded promising results in this patient.

PMID- 22977679
TI  - Implications of anomalous pectoralis muscle in reconstructive breast surgery: the
      oblique pectoralis anterior.
AB  - INTRODUCTION: Many case reports have described anatomical variants of the
      pectoralis muscles. However, there is a paucity of published literature on the
      consequence of such presentations in reconstructive breast surgery. METHODS: A 45
      year-old female patient with breast cancer presented for left mastectomy and
      immediate reconstruction with tissue expander. During mastectomy, she was noted
      to have an extra muscle anterior to her pectoralis major muscle. This variant had
      not previously been described in the literature and was therefore named the
      oblique pectoralis anterior. After inspection of the aberrant musculature, the
      decision was made to release the inferolateral insertion of the accessory muscle
      with the inferior edge of pectoralis major. An adequate pocket for the expander
      was created. RESULTS: After routine expansion and implant exchange, muscular
      coverage of the implant from pectoralis major and the oblique pectoralis anterior
      muscle approximated 70%. The patient was left with good symmetry and a cosmetic
      result, despite the challenges presented by her anomalous chest wall musculature.
      DISCUSSION: Prior knowledge of the various anatomic aberrations described in the
      literature can prepare a surgeon to properly incorporate and utilize the variant
      anatomy, should it be encountered, to benefit the outcome of the operation.

PMID- 22977680
TI  - Antioxidant activities and determination of phenolic compounds isolated from
      oriental plums (Soldam, Oishiwase and Formosa).
AB  - The purposes of this study were to determine phenolic compounds and to evaluate
      antioxidant activities of plums (Soldam, Oishiwase and Formosa). Soldam contains
      the highest amount of total phenolics among cultivars (Formosa: 4.0%, Oishiwase:
      3.3%, Soldam: 6.4% for total phenolic) as well as the total flavonoids of which
      constituents were mainly myricetin and anthocyanidin. The antioxidant activities
      were measured by DPPH, ABTS radical scavenging, and SOD-like activities. The DPPH
      radical scavenging activity of Korean plum extracts (200 ug/mL) showed more than
      43%, and the Soldam turned out to be the highest : ID(50) value: 160-177 ug/mL
      for Formosa and Oishiwase; 58-64 ug/mL for Soldam. The ABTS radical scavenging
      activity of Korean plum extracts (200 ug/mL) was found to be more than 50%. The
      SOD-like activity of Korean plum extracts (200 ug/mL) showed more than 70%. Among
      three kinds of cultivars, Soldam had the highest antioxidant activity. The
      nitrite scavenging activity of Soldam was 61.5%, which is the highest, compared
      with that of the other cultivars, about 50%. From these results, Korean plums
      turned out to be phytochemical rich fruit as well as to show high antioxidant
      activities.

PMID- 22977681
TI  - Anti-obesity effect of resveratrol-amplified grape skin extracts on 3T3-L1
      adipocytes differentiation.
AB  - Resveratrol (3,4,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skin,
      grape products, and peanuts as well as red wine, has been reported to have
      various biological and pharmacological properties. The purpose of this study was
      to investigate the anti-obesity effect of resveratrol-amplified grape skin
      extracts on adipocytes. The anti-obesity effects of grape skin extracts were
      investigated by measuring proliferation and differentiation in 3T3-L1 cells. The
      effect of grape skin ethanol extracts on cell proliferation was detected by the
      MTS assay. The morphological changes and degree of adipogenesis of preadipocyte
      3T3-L1 cells were measured by Oil Red-O staining assay. Treatment with extracts
      of resveratrol-amplified grape skin decreased lipid accumulation and glycerol-3
      phosphate dehydrogenase activity without affecting 3T3-L1 cell viability. Grape
      skin extract treatment resulted in significantly attenuated expression of key
      adipogenic transcription factors, including peroxisome proliferator-activated
      receptor, CCAAT/enhancer-binding proteins, and their target genes (FAS, aP2, SCD
      1, and LPL). These results indicate that resveratrol-amplified grape skin
      extracts may be useful for preventing obesity by regulating lipid metabolism.

PMID- 22977682
TI  - Effect of resveratrol on the metastasis of 4T1 mouse breast cancer cells in vitro
      and in vivo.
AB  - We investigated the effects of resveratrol on metastasis in in vitro and in vivo
      systems. 4T1 cells were cultured in the presence of various concentrations (0-30
      umol/L) of resveratrol. For experimental metastasis, BALB/c mice were injected
      intravenously with 4T1 cells in the tail vein, and were orally administered
      various concentrations (0, 100, or 200 mg/kg Body weight) of resveratrol for 21
      days. After resveratrol treatment, cell adhesion, wound migration, invasion, and
      MMP-9 activity were significantly decreased in a dose-dependent manner in 4T1
      cells (P < 0.05). The numbers of pulmonary nodules were significantly decreased
      in mice fed the resveratrol (P < 0.05). The plasma MMP-9 activity was decreased
      in response to treatment with resveratrol in mice (P < 0.05). We conclude that
      resveratrol inhibits cancer metastasis both in vitro and in vivo, and this
      inhibition is likely due to the decrease in MMP-9 activity caused by resveratrol.

PMID- 22977683
TI  - Effect of quercetin on impaired immune function in mice exposed to irradiation.
AB  - Radiation used in cancer treatment may cause side effects such as inflammation.
      Quercetin is a polyphenol that reduces inflammation. This study evaluated the
      recovery efficacy of quercetin on impaired immune function in irradiation-induced
      inflammatory mice. Quercetin administered at two concentrations of 10 and 40
      mg/kg body weight was initiated 2 weeks before irradiation and was continued 30
      days after irradiation. The animals exposed/not exposed to radiation were
      sacrificed on radiation days 10 and 30. Splenocyte proliferation, which was
      diminished after irradiation, was enhanced significantly by quercetin
      supplementation after 30 days of irradiation. Cytokine secretion increased in the
      radiation group compared to that in the non-radiation control group. After 30
      days of radiation, interleukin (IL)-1beta and IL-6 secretion decreased
      significantly in the radiation-quercetin groups. When quercetin was administered
      for 44 days, it showed a possible protective effect against irradiation-induced
      inflammation in mice. Quercetin could be beneficial in the recovery of
      irradiation-induced increases in cytokine secretion.

PMID- 22977684
TI  - The antihypertensive effect of ethyl acetate extract of radish leaves in
      spontaneously hypertensive rats.
AB  - Radish (Raphanus sativus L.) is a cruciferous vegetable, and its leaves have
      antioxidant and anticancer properties. This study was conducted to evaluate the
      effects of ethyl acetate extracts from radish leaves on hypertension in 11-week
      old spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into 3
      groups of 6 rats each on the basis of initial systolic blood pressure (SBP) and
      were treated with oral administration of radish leaf extract (0, 30, or 90 mg/kg
      body weight [bw], respectively) for 5 weeks. Six Wistar rats were used as
      normotensive controls. The amount of the radish leaf extract had no effect on
      body weight. The SBP of the SHRs showed a decreasing trend with the consumption
      of the radish leaf extract. In the third week, the SBP of the group fed 90 mg
      extract/kg bw reduced from 214 mmHg to 166 mmHg and was significantly lower than
      that of the normotensive and hypertensive controls. The extract did not show a
      significant effect on the angiotensin-converting enzyme (ACE) activity in the
      serum, kidney, and lung. The extract increased the concentration of NO in serum
      and the activities of antioxidant enzymes such as glutathione peroxidase and
      catalase in red blood cells (RBCs). The serum concentrations of Na(+) and K(+)
      were not significantly different between all groups. However, the fecal
      concentrations of Na(+) and K(+) increased; the fecal concentrations of Na(+) and
      K(+) for the normotensive and hypertensive controls were not different. Urinary
      excretion of Na(+) was higher in the normotensive Wistar rats than in the SHRs,
      while that of K(+) was not significantly different. These findings indicate that
      consumption of radish leaves might have had antihypertensive effects in SHRs by
      increasing the serum concentration of NO and fecal concentration of Na(+) and
      enhancing antioxidant activities.

PMID- 22977685
TI  - Effects of kimchi supplementation on blood pressure and cardiac hypertrophy with
      varying sodium content in spontaneously hypertensive rats.
AB  - We tested the effects of dietary intake of freeze-dried Korean traditional
      fermented cabbage (generally known as kimchi) with varying amounts of sodium on
      blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs).
      Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and
      the SHRs were divided into four groups. The SHR group was fed a regular diet
      without kimchi supplementation, the SHR-L group was fed the regular diet
      supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was
      provided in a freeze-dried form, the SHR-M group was supplemented with medium
      levels of sodium kimchi containing 2.4% salt, and the SHR-H group was
      supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was
      measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart
      and left ventricle weights and cardiac histology. SHRs showed higher blood
      pressure compared to that in WKY rats, which was further elevated by consuming
      high sodium containing kimchi but was not influenced by supplementing with low
      sodium kimchi. None of the SHR groups showed significant differences in cardiac
      and left ventricular mass or cardiomyocyte size. Levels of serum biochemical
      parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic
      transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not
      different among the groups. Elevations in serum levels of aldosterone in SHR rats
      decreased in the low sodium kimchi group. These results suggest that consuming
      low sodium kimchi may not adversely affect blood pressure and cardiac function
      even under a hypertensive condition.

PMID- 22977686
TI  - Sorghum extract exerts an anti-diabetic effect by improving insulin sensitivity
      via PPAR-gamma in mice fed a high-fat diet.
AB  - This study investigated the hypothesis that a sorghum extract exerts anti
      diabetic effects through a mechanism that improves insulin sensitivity via
      peroxisome proliferator-activated receptor gamma (PPAR-gamma) from adipose
      tissue. Seven C57BL/6 mice were fed an AIN-93M diet with fat consisting of 10% of
      total energy intake (LF) for 14 weeks, and 21 mice were fed a high-fat AIN diet
      with 60% of calories derived from fat (HF). From week 8, the HF diet-fed mice
      were orally administered either saline (HF group), 0.5% (0.5% SE group), or 1%
      sorghum extract (1% SE group) for 6 weeks (n = 7/group). Perirenal fat content
      was significantly lower in the 0.5% SE and 1% SE groups than that in the HF mice.
      Levels of total and low-density lipoprotein cholesterol, triglycerides, glucose,
      and the area under the curve for glucose were significantly lower in mice
      administered 0.5% SE and 1% SE than those in HF mice. Serum insulin level was
      significantly lower in mice administered 1% SE than that in HF mice or those
      given 0.5% SE. PPAR-gamma expression was significantly higher, whereas the
      expression of tumor necrosis factor-alpha was significantly lower in mice given
      1% SE compared to those in the HF mice. Adiponectin expression was also
      significantly higher in mice given 0.5% SE and 1% SE than that in the HF mice.
      These results suggest that the hypoglycemic effect of SE may be related with the
      regulation of PPAR-gamma-mediated metabolism in this mouse model.

PMID- 22977688
TI  - Comparative study on body shape satisfaction and body weight control between
      Korean and Chinese female high school students.
AB  - This study was conducted to compare body shape satisfaction, body image
      perception, weight control status, and dietary habits of Korean and Chinese
      female high school students in order to provide information for proper body image
      perception of adolescents. 221 students in Yongin, a city in Korea, and 227
      students in Weihai, a city in China, were surveyed using questionnaires. Body
      shape satisfaction was significantly higher in Chinese students (P < 0.001)
      compared to Korean students. 76.2% of Korean students and 72.7% of Chinese
      students wanted a thinner body shape than their present body shapes. Experiences
      of weight control, laxative or diuretics uses, eating during weight control, and
      vomiting after eating were significantly higher in Korean students (P < 0.05-P <
      0.001) compared to Chinese students. The score for dietary habits was
      significantly higher in Chinese students (P < 0.001) compared to Korean students,
      suggesting a more desirable dietary habit among Chinese students. Students of
      both countries showed a significantly positive correlation between body shape
      satisfaction and dietary habits, suggesting that as body shape satisfaction
      increases, dietary habits become more desirable. In conclusion, Korean female
      students showed a more distorted body image perception and had more poor dietary
      habits than Chinese students. Nutritional education for the establishment of
      normal body weight, proper body image perception, and healthy dietary habits are
      needed.

PMID- 22977687
TI  - Meal skipping relates to food choice, understanding of nutrition labeling, and
      prevalence of obesity in Korean fifth grade children.
AB  - This study was performed to investigate the differences in food choice, nutrition
      labeling perceptions, and prevalence of obesity due to meal skipping in Korean
      elementary school children. A national survey was performed in 2010 to collect
      data on food intake frequency, understanding of nutrition labeling, and body mass
      index from 2,335 fifth grade students in 118 elementary schools selected from 16
      metropolitan local governments by stratified cluster sampling. The data were
      analyzed using the SAS 9.1 and SUDAAN 10.0 packages. Students who consumed three
      meals for 6-7 days during the past week were classified into the regular meal
      eating (RM) group (n = 1,476) and those who did not were placed into the meal
      skipping (MS) group (n = 859). The daily intake frequency of fruits, vegetables,
      kimchi, and milk was significantly lower in the MS group compared to that in the
      RM group (P < 0.001), whereas the daily intake frequency of soft drinks and
      instant noodles (ramyeon) was significantly higher in the MS group than that in
      the RM group (P < 0.05). The MS group demonstrated a significantly lower degree
      of understanding with regard to nutrition labeling and high calorie foods
      containing low nutritional value than that in the RM group. The distribution of
      obesity based on the percentile criteria using the Korean growth chart was
      different between the MS and RM groups. The MS group (8.97%) had a higher
      percentage of obese subjects than that in the RM group (5.38%). In conclusion,
      meal skipping was related to poor food choice, low perception of nutrition
      labeling, and a high prevalence of obesity in Korean fifth grade children.

PMID- 22977689
TI  - A study on dietary habits, health related lifestyle, blood cadmium and lead
      levels of college students.
AB  - This study was performed in order to investigate dietary habits, health related
      lifestyle and blood cadmium and lead levels in female college students. 80
      college students (43 males and 37 females) participated in the survey
      questionnaires. Body weight and height, blood pressure, and body composition were
      measured. The systolic blood pressure of male and female students were 128.9 +/-
      13.9 and 109.8 +/- 12.0, respectively. The diastolic blood pressure of male and
      female students were 77.1 +/- 10.3 and 66.0 +/- 6.9, respectively, showing that
      male students had significantly higher blood pressure than female students (P <
      0.001). The BMI of male and female students were 23.4 +/- 3.3 and 20.2 +/- 2.3,
      respectively. Most male students were in the range of being overweight. The
      dietary habits score of female students was significantly higher than that of
      male students (P < 0.01).The blood cadmium level of male and female students were
      0.54 +/- 0.23 and 0.52 +/- 0.36, respectively. There was no significant
      difference between male and female students. The blood lead level of male and
      female students were 1.09 +/- 0.49 and 0.59 +/- 0.45, respectively. The blood
      lead level of male students was significantly higher than that of female students
      (P < 0.001). The blood cadmium level of smokers and nonsmokers were 0.69 +/- 0.29
      and 0.49 +/- 0.29 respectively (P < 0.05). The blood cadmium level of smokers was
      significantly higher than that of nonsmokers (P < 0.05). The blood lead level of
      smokers and nonsmokers were 1.09 +/- 0.43 and 0.80 +/- 0.54, respectively. The
      blood lead level of smokers was significantly higher than that of nonsmokers (P <
      0.05). Therefore, proper nutritional education programs are required for college
      students in order to improve their dietary and health related living habits.

PMID- 22977690
TI  - Dietary patterns based on carbohydrate nutrition are associated with the risk for
      diabetes and dyslipidemia.
AB  - Several studies have been conducted on dietary patterns based on carbohydrate
      nutrition in Asian populations. We examined the cross-sectional associations in
      dietary patterns based on carbohydrate nutrition, including the glycemic index
      (GI) with dyslipidemia and diabetes among the Korean adult population. We
      analyzed 9,725 subjects (3,795 men and 5,930 women, >= 20 years) from the Fourth
      Korea National Health and Nutrition Examination Survey. Dietary information was
      collected using single 24-hour recall. Reduced rank regression was used to derive
      dietary patterns from 22 food groups as predictor variables and four dietary
      factors related to the quantity and quality of carbohydrates as response
      variables. Two dietary patterns were identified: 1) the balanced pattern was
      characterized by high intake of various kinds of foods including white rice, and
      2) the rice-oriented pattern was characterized by a high intake of white rice but
      low intake of vegetables, fruits, meat, and dairy products. Both patterns had
      considerable amounts of total carbohydrate, but GI values differed. The rice
      oriented pattern was positively associated with hypertriglyceridemia in men and
      low high density lipoprotein-cholesterol in both men and women. The balanced
      pattern had no overall significant association with the prevalence of
      dyslipidemia or diabetes, however, men with energy intake above the median showed
      a reduced prevalence of diabetes across quintiles of balanced pattern scores. The
      results show that dietary patterns based on carbohydrate nutrition are associated
      with prevalence of dyslipidemia and diabetes in the Korean adult population.

PMID- 22977691
TI  - A study on the model of homebound senior's meal satisfaction related to the
      quality of life.
AB  - This study was conducted to develop a construct model regarding the daily
      activities, emotional security provided by food, enjoyment of food, level of
      satisfaction with delivered food, and the quality of life of homebound seniors
      who benefitted from meal delivery programs. The data were analyzed by SAS 9.2 and
      the Structural Equation Model (SEM), which was created by Analysis of Moment
      Structure (AMOS) 5.0 packages. The reliability of the data was confirmed by an
      exploratory factor analysis and through a Cronbach's alpha coefficient, and the
      measurement model proved to be appropriate by a confirmatory factor analysis of
      the measurement model in conjunction with AMOS. The results of the correlations
      between all the variables showed significant positive correlations (P < 0.05).
      The path analysis demonstrated that the daily activities (P < 0.01) and the
      emotional security created by food (P < 0.05) had positive correlations with the
      foodservice satisfaction (P < 0.05), while the daily activities (P < 0.05), the
      sense of emotional security made by food (P < 0.05), and food enjoyment (P <
      0.05) also presented significant positive correlations with the quality of life.
      However, the food service satisfaction was shown to directly, but not
      significantly, affect the quality of life. This revealed that the current meal
      delivery programs needed to be improved in several directions.

PMID- 22977692
TI  - How do the work environment and work safety differ between the dry and wet
      kitchen foodservice facilities?
AB  - In order to create a worker-friendly environment for institutional foodservice,
      facilities operating with a dry kitchen system have been recommended. This study
      was designed to compare the work safety and work environment of foodservice
      between wet and dry kitchen systems. Data were obtained using questionnaires with
      a target group of 303 staff at 57 foodservice operations. Dry kitchen facilities
      were constructed after 2006, which had a higher construction cost and more
      finishing floors with anti-slip tiles, and in which employees more wore non-slip
      footwear than wet kitchen (76.7%). The kitchen temperature and muscular pain were
      the most frequently reported employees' discomfort factors in the two systems,
      and, in the wet kitchen, "noise of kitchen" was also frequently reported as a
      discomfort. Dietitian and employees rated the less slippery and slip related
      incidents in dry kitchens than those of wet kitchen. Fryer area, ware-washing
      area, and plate waste table were the slippery areas and the causes were different
      between the functional areas. The risk for current leakage was rated
      significantly higher in wet kitchens by dietitians. In addition, the ware-washing
      area was found to be where employees felt the highest risk of electrical shock.
      Muscular pain (72.2%), arthritis (39.1%), hard-of-hearing (46.6%) and
      psychological stress (47.0%) were experienced by employees more than once a
      month, particularly in the wet kitchen. In conclusion, the dry kitchen system was
      found to be more efficient for food and work safety because of its superior
      design and well managed practices.

PMID- 22977694
TI  - Management of Persistent Cerebrospinal Fluid Leakage Following Thoraco-lumbar
      Surgery.
AB  - STUDY DESIGN: This was a retrospective study of patients who had developed a
      dural tear after thoracic and lumbar spine surgery that was not recognized during
      the surgery, and was treated either by lumbar drainage or over-sewing of the
      wounds. PURPOSE: To revisit the treatment strategies in postoperative dural leaks
      and present our experience with over-sewing of the wound and lumbar drainage.
      OVERVIEW OF LITERATURE: Unintended durotomy is a frequent complication of spinal
      surgery. Management of subsequent cerebrospinal fluid leakage remains
      controversial. There is no distinct treatment guideline according to the etiology
      in the current literature. METHODS: The records of 368 consecutive patients who
      underwent thoracic and/or lumbar spine surgery from 2006 throug h 2010 were
      retrospectively reviewed. Seven cerebrospinal fluid fistulas and five
      pseudomeningoceles were noted in 12 (3.2%) procedures. Cerebrospinal fluid
      diversion by lumbar drainage in five pseudomeningoceles and over-sewing of wounds
      in seven cerebrospinal fluid fistulas employed in 12 patients. Clinical grading
      was evaluated by Wang. RESULTS: Of the 12 patients who had a dural tear, 5 were
      managed successfully with lumbar drainage, and 7 with oversewing of the wound.
      The clinical outcomes were excellent in 9 patients, good in 2, and poor in 1.
      Complications such as neurological deficits, or superficial or deep wound
      infections did not develop. A recurrence of the fistula or pseudomeningocele
      after the treatment was not seen in any of our patients. CONCLUSIONS:
      Pseudomeningoceles respond well to lumbar drainage, whereas over-sewing of the
      wound is an alternative treatment option in cerebrospinal fluid fistulas without
      neurological compromise.

PMID- 22977695
TI  - The validation of ultrasound-guided lumbar facet nerve blocks as confirmed by
      fluoroscopy.
AB  - STUDY DESIGN: This is a prospective study. PURPOSE: To develop a methodological
      approach for conducting ultrasound-guided lumbar facet nerve block by defining
      essential ultrasound-guided landmarks in order to assess the feasibility of this
      method. OVERVIEW OF LITERATURE: The current role of ultrasound guidance for
      musculoskeletal intervention treatments has been reported upon in previous
      literature. METHODS: Ultrasound-guided facet nerve block was done in 95 segments
      for 50 patients with chronic back pain by facet arthropathy. After the surface
      landmarks of the spinous process and iliac crest line were confirmed,
      longitudinal facet views were obtained by a curved array transducer to identify
      the different spinal segments. The spinous process and facet joint with
      transverse process were delineated by transverse sonograms at each level and the
      target point for the block was defined as lying on the upper edge of the
      transverse process. The needle was inserted toward the target point. After a
      contrast injection, the placement of the needle and contrast was checked by
      fluoroscopy. RESULTS: Eighty-seven segments (91.6%) could be guided successfully
      to the right facet nerve block by using ultrasound. After fluoroscopic control, 8
      needles had to be corrected because of problems with other segments (3 cases) and
      lamina placements (5 cases). For the 42 patients who underwent successful block
      by ultrasound, however, the mean visual analogue score for back pain was improved
      from 6.2 +/- 0.9 before the block to 4.0 +/- 1.0 after the block (p = 0.001).
      CONCLUSIONS: Ultrasound-guided longitudinal facet view and the surface landmarks
      of the spinous process and iliac crest line seems to be a promising guidance
      technique for the lumbar facet nerve block technique.

PMID- 22977697
TI  - Effect of psychological status on outcome of posterior lumbar interbody fusion
      surgery.
AB  - STUDY DESIGN: Prospective longitudinal study. PURPOSE: To determine if
      preoperative psychological status affects outcome in spinal surgery. OVERVIEW OF
      LITERATURE: Low back pain is known to have a psychosomatic component. Increased
      bodily awareness (somatization) and depressive symptoms are two factors that may
      affect outcome. It is possible to measure these components using questionnaires.
      METHODS: Patients who underwent posterior interbody fusion (PLIF) surgery were
      assessed preoperatively and at follow-up using a self-administered questionnaire.
      The visual analogue scale (VAS) for back and leg pain severity and the Oswestry
      Disability Index (ODI) were used as outcome measures. The psychological status of
      patients was classified into one of four groups using the Distress and Risk
      Assessment Method (DRAM); normal, at-risk, depressed somatic and distressed
      depressive. RESULTS: Preoperative DRAM scores showed 14 had no psychological
      disturbance (normal), 39 were at-risk, 11 distressed somatic, and 10 distressed
      depressive. There was no significant difference between the 4 groups in the mean
      preoperative ODI (analysis of variance, p = 0.426). There was a statistically and
      clinically significant improvement in the ODI after surgery for all but
      distressed somatic patients (9.8; range, -5.2 to 24.8; p = 0.177). VAS scores for
      all groups apart from the distressed somatic showed a statistically and
      clinically significant improvement. Our results show that preoperative
      psychological state affects outcome in PLIF surgery. CONCLUSIONS: Patients who
      were classified as distressed somatic preoperatively had a less favorable outcome
      compared to other groups. This group of patients may benefit from formal
      psychological assessment before undergoing PLIF surgery.

PMID- 22977696
TI  - Computer-assisted C1-C2 Transarticular Screw Fixation "Magerl Technique" for
      Atlantoaxial Instability.
AB  - STUDY DESIGN: A retrospective study. PURPOSE: To evaluate the surgical results of
      computer-assisted C1-C2 transarticular screw fixation for atlantoaxial
      instability and the usefulness of the navigation system. OVERVIEW OF LITERATURE:
      We used a computed tomography (CT)-based computer navigation system in planning
      and screw insertion in Magerl's procedure, which provides the most rigid
      atlantoaxial fusion, to avoid risk of vertebral artery (VA) tear by avoiding high
      riding VA during screw insertion. METHODS: Twenty patients who underwent
      atlantoaxial fusion under the CT-based navigation system were studied. The mean
      observation period was 33.5 months. The evaluated items included the existence of
      VA stenosis by preoperative magnetic resonance angiography, surgical time, blood
      loss volume, Japanese Orthopaedic Association (JOA) score and Ranawat's pain
      criteria before surgery and at final follow-up, postoperative screw position
      evaluated by CT, and bony fusion. RESULTS: The mean operation time was 205
      minutes, with the mean blood loss volume of 242 ml. The mean JOA score was 11.6
      points before surgery and 13.7 at final follow-up. Occipital and/or cervical pain
      presented before operation was remitted or resolved in all patients. Evaluation
      of screw insertion by CT revealed correct penetration to atlantoaxial joints,
      with a perforation rate of 2.6%. There was no complication, including VA tear,
      and all patients who were followed-up during one year or more after surgery
      achieved bony fusion. Some subjects who appeared inappropriate for surgery from
      CT images were assessed as eligible for surgery based on the evaluation results
      obtained using the navigation system. CONCLUSIONS: It was demonstrated that the
      CT-based navigation system is an effective support device for Magerl's procedure.

PMID- 22977698
TI  - Evaluation of role of anterior debridement and decompression of spinal cord and
      instrumentation in treatment of tubercular spondylitis.
AB  - STUDY DESIGN: Prospective study with simple randomization. PURPOSE: To evaluate
      the results of anterior spinal instrumentation, debridement and decompression of
      cord and compare it with results of a similar procedure done without the use of
      anterior instrumentation. OVERVIEW OF LITERATURE: Use of anterior spinal
      instrumentation in treatment of tubercular spondylitis is still an infrequently
      followed modality of treatment and data regarding its usefulness are still
      emerging. METHODS: Thirty-two patients of tubercular paraplegia with involvement
      of dorsal and dorso-lumbar vertebrae were operated with anterior spinal cord
      decompression, autofibular strut grafting with anterior instrumentation in 18
      patients and no implant in 14 patients. Results were compared on the basis of
      improvement in Frankel grade, correction of local kyphosis, decrease in canal
      compromise and further progression of kyphosis. RESULTS: The mean local kyphosis
      correction in the immediate postoperative period was 24.1 degrees  in the
      instrumented group and was 6.1 degrees  in the non instrumented group. The mean
      late loss of correction of local kyphosis at 3 years follow-up was 1.7 degrees 
      in the instrumented and 6.7 degrees  in the non instrumented group. The mean
      improvement in canal compression was 39.5% in the instrumented group and 34.8% in
      the non instrumented group. CONCLUSIONS: In treatment of tubercular spondylitis
      by anterior debridement and decompression of the spinal cord and autofibular
      strut grafting, the use of instrumentation has no relation with the improvement
      in neurological status, however the correction of local kyphosis and prevention
      of further progression of local kyphosis was better with the use anterior spinal
      instrumentation.

PMID- 22977699
TI  - Percutaneous Pedicle Screw Fixation of a Hangman's Fracture Using Intraoperative,
      Full Rotation, Three-dimensional Image (O-arm)-based Navigation: A Technical Case
      Report.
AB  - Surgical treatment of a hangman's fractures is technically demanding, even when
      using the standard open procedure. In this case report, a type II hangman's
      fracture was treated by percutaneous posterior screw fixation, without a midline
      incision, using intraoperative, full rotation, three-dimensional (3D) image (O
      arm)-based navigation. A 48-year-old woman was injured in a motor vehicle
      accident and diagnosed with a unilateral hangman's fracture associated with
      subluxation of the C2 vertebral body on C3. After attaching the reference arc of
      the 3D-imaging system to the headholder, the cervical spine was screened using an
      O-arm without anatomical registration. Drilling and screw fixation were performed
      using a guide tube while referring to the reconstructed 3D-anatomical views. The
      operation was successfully completed without technical difficulties or
      neurovascular complications. This percutaneous procedure requires less dissection
      of normal tissue, which may allow earlier recovery. However, further validation
      of this procedure for its effectiveness and safety is required.

PMID- 22977700
TI  - Surgical treatment of t1-2 disc herniation with t1 radiculopathy: a case report
      with review of the literature.
AB  - The prevalence of intervertebral disc herniation (IDH) of the thoracic spine is
      rare compared to the cervical or lumbar spine. In particular, IDH of the upper
      thoracic spine is extremely rare. We report the case of T1-2 IDH and its
      treatment, with a literature review. A 37-year-old male patient visited our
      hospital due to radiating pain at the left upper extremity and weakness of grip
      power. In cervical spine magnetic resonance images, T1-2 disc space showed
      herniated disc material and compressed T1 root was identified. Laminoforaminotomy
      was performed with a posterior approach. The radiating pain and weakness of grip
      power improved immediately after the surgery. Of patients who show radiating pain
      or numbness at the medial aspect of forearm, or weakness of intrinsic muscle of
      hand, can be suspected to have T1 radiculopathy. A detailed physical examination
      and a radiologic evaluation including this area should be required for the T1
      radiculopathy.

PMID- 22977701
TI  - Solitary epidural lipoma with ipsilateral facet arthritis causing lumbar
      radiculopathy.
AB  - A 55-year-old obese man (body mass index, 31.6 kg/m(2)) presented radiating pain
      and motor weakness in the left leg. Magnetic resonance imaging showed an epidural
      mass posterior to the L5 vertebral body, which was isosignal to subcutaneous fat
      and it asymmetrically compressed the left side of the cauda equina and the
      exiting left L5 nerve root on the axial T1 weighted images. Severe arthritis of
      the left facet joint and edema of the bone marrow regarding the left pedicle were
      also found. As far as we know, there have been no reports concerning a solitary
      epidural lipoma combined with ipsilateral facet arthorsis causing lumbar
      radiculopathy. Solitary epidural lipoma with ipsilateral facet arthritis causing
      lumbar radiculopathy was removed after the failure of conservative treatment.
      After decompression, the neurologic deficit was relieved. At a 2 year follow-up,
      motor weakness had completely recovered and the patient was satisfied with the
      result. We recommend that a solitary epidural lipoma causing neurologic deficit
      should be excised at the time of diagnosis.

PMID- 22977702
TI  - Left second rib exostosis, spinal cord compression and left upper thoracic
      scoliosis: a rare triad.
AB  - Exostosis of the rib with neural foraminal extension as a cause of spinal cord
      compression and scoliosis has to the best of our knowledge not been reported. We
      describe a young male with hereditary multiple exostosis who presented with a
      spastic gait, lower limb weakness and a deformity of the upper back. Radiographic
      imaging revealed a lesion arising from the left second rib which was encroaching
      the spinal canal and a scoliotic deformity of the upper thoracic spine. Through a
      single T shaped posterior approach he underwent a decompressive laminectomy of T1
      and T2 vertebra and excision of the lesion. The diagnosis of osteochondroma was
      confirmed by histopathological studies. He was followed up at one year when his
      neurological condition had returned to normal however the scoliosis had
      increased.

PMID- 22977703
TI  - Recurrent malignant fibrous histiocytoma in psoas muscle: a case report.
AB  - Malignant fibrous histiocytoma is one of the most common sarcomas that occur in
      soft tissue, it usually develops in old age individuals and the incidence is
      similar between the genders. We report here on a case with invasive local
      recurrence after surgical resection of a malignant fibrous histiocytoma that
      occurred in the left psoas muscle of a 69-year-old male patient. The patient was
      first admitted to our hospital with a primary lesion in the left lower abdomen,
      as seen on magnetic resonance imaging. We report here on a rare case of a
      malignant fibrous histicytoma in the psoas muscle.

PMID- 22977704
TI  - Motion Induced Artifact Mimicking Cervical Dens Fracture on the CT Scan: A Case
      Report.
AB  - The diagnostic performance of helical computed tomography (CT) is excellent.
      However, some artifacts have been reported, such as motion, beam hardening and
      scatter artifacts. We herein report a case of motion-induced artifact mimicking
      cervical dens fracture. A 60-year-old man was involved in a motorcycle accident
      that resulted in cervical spinal cord injury and quadri plegia. Reconstructed CT
      images of the cervical spine showed a dens fracture. We assessed axial CT in
      detail, and motion artifact was detected.

PMID- 22977705
TI  - Letter: treatment of acute tuberculous spondylitis by the spinal shortening
      osteotomy: a technical notes and case illustrations.

PMID- 22977706
TI  - Dear editor of asian spinal journal.

PMID- 22977707
TI  - Decreased Immunoreactivities of the Chloride Transporters, KCC2 and NKCC1, in the
      Lateral Superior Olive Neurons of Kanamycin-treated Rats.
AB  - OBJECTIVES: From our previous study about the weak expressions of potassium
      chloride (KCC2) and sodium-potassium-2 chloride (NKCC1) co-transporters in the
      lateral superior olive (LSO) in circling mice, we hypothesized that partially
      damaged cochlea of circling mice might be a cause of the weak expressions of KCC2
      or NKCC1. To test this possibility, we reproduced the altered expressions of KCC2
      and NKCC1 in the LSO of rats, whose cochleae were partially destroyed with
      kanamycin. METHODS: Rat pups were treated with kanamycin from postnatal (P)3 to
      P8 (700 mg/kg, subcutaneous injection, twice a day) and sacrificed for
      immunohistochemical analysis, scanning electron microscope (SEM) and auditory
      brain stem response. RESULTS: The SEM study revealed partially missing hair cells
      in P9 rats treated with kanamycin, and the hearing threshold was elevated to
      63.8+/-2.5 dB SPL (4 ears) at P16. Both KCC2 and NKCC1 immunoreactivities were
      more prominent in control rats on P16. On 9 paired slices, the mean densities of
      NKCC1 immunoreactivities were 118.0+/-1.0 (control) and 112.2+/-1.2 (kanamycin
      treated), whereas those of KCC2 were 115.7+/-1.5 (control) and 112.0+/-0.8
      (kanamycin treated). CONCLUSION: We concluded that weak expressions of KCC2 and
      NKCC1 in circling mice were due to partial destruction of cochleae.

PMID- 22977708
TI  - Binaural electric-acoustic interactions recorded from the inferior colliculus of
      Guinea pigs: the effect of masking observed in the central nucleus of the
      inferior colliculus.
AB  - OBJECTIVES: To investigate the electric-acoustic interactions within the inferior
      colliculus of guinea pigs and to observe how central masking appears in invasive
      neural recordings of the inferior colliculus (IC). METHODS: A platinum-iridium
      wire was inserted to scala tympani through cochleostomy with a depth no greater
      than 1 mm for intracochlear stimulation of electric pulse train. A 5 mm 100 um,
      single-shank, thin-film, penetrating recording probe was inserted perpendicularly
      to the surface of the IC in the coronal plane at an angle of 30-40 degrees  off
      the parasagittal plane with a depth of 2.0-2.5 mm. The peripheral and central
      masking effects were compared using electric pulse trains to the left ear and
      acoustic noise to the left ear (ipsilateral) and to the right ear
      (contralateral). Binaural acoustic stimuli were presented with different time
      delays and compared with combined electric and acoustic stimuli. The averaged
      evoked potentials and total spike numbers were measured using thin-film
      electrodes inserted into the central nucleus of the IC. RESULTS: Ipsilateral
      noise had more obvious effects on the electric response than did contralateral
      noise. Contralateral noise decreased slightly the response amplitude to the
      electric pulse train stimuli. Immediately after the onset of acoustic noise, the
      response pattern changed transiently with shorter response intervals. The effects
      of contralateral noise were evident at the beginning of the continuous noise. The
      total spike number decreased when the binaural stimuli reached the IC most
      simultaneously. CONCLUSION: These results suggest that central masking is quite
      different from peripheral masking and occurs within the binaural auditory system,
      and this study showed that the effect of masking could be observed in the IC
      recording. These effects are more evident and consistent with the psychophysical
      data from spike number analyses than with the previously reported gross potential
      data.

PMID- 22977709
TI  - Apoptosis Progression in the Hair Cells in the Organ of Corti of GJB2 Conditional
      Knockout Mice.
AB  - OBJECTIVES: Apoptosis may play an important role in the mechanism underlying the
      GJB2 gene conditional knockout (cCx26) mice cochlear cell death. The objective of
      this study was to explore the the damage mode of the outer hair cells (OHCs) and
      its real time point of apoptosis and provide information to further explore the
      role of apoptosis in the happening of hearing loss in cCx26 mice. METHODS:
      Cochleae from mice at various developmental stages (P8, P12, and P21) were
      dissected out and first used to be observed under the scanning electron
      microscope (SEM). Basilar membranes from mice at P8, P14, P18, and P21 were
      stained by fluorescein isothiocyanate-conjugated phalloidin and propidium iodide
      (PI) and examined under confocal microscope. RESULTS: The loss of OHCs of cCx26
      knockout mice was first set between P12 and P21 under SEM. Whole mount phalloidin
      and PI staining revealed that obvious apoptotic appearance of the OHCs surface
      morphology was observed at P18. CONCLUSION: Typical apoptotic morphology was
      found in the OHCs in the organ of Corti of the cCx26 mice at P18. This may
      provide information to further study the role of apoptosis in the occurrence of
      hearing loss of cCx26 mice.

PMID- 22977710
TI  - In VitroStreptococcus pneumoniae Biofilm Formation and In Vivo Middle Ear Mucosal
      Biofilm in a Rat Model of Acute Otitis Induced by S. pneumoniae.
AB  - OBJECTIVES: Streptococcus pneumoniae is one of the most common pathogens of
      otitis media (OM) that exists in biofilm, which enhances the resistance of
      bacteria against antibiotic killing and diagnosis, compared to the free-floating
      (planktonic) form. This study evaluated biofilm formation by S. pneumoniae on an
      abiotic surface and in the middle ear cavity in a rat model of OM. METHODS: In
      vitro biofilm formation was evaluated by inoculation of a 1:100 diluted S.
      pneumoniae cell suspension in a 96-well microplate. Adherent cells were
      quantified spectrophotometrically following staining with crystal violet by
      measurement of optical density at 570 nm. The ultrastructure of pneumococcal
      biofilm was assessed by scanning electron microscopy (SEM). For in vitro biofilm
      study, S. pneumoniae cell suspensions containing 1*10(7) colony forming units
      were injected through transtympanic membrane into the middle ear cavity of
      Sprague Dawley rats. The ultrastructure of middle ear mucus was observed by SEM 1
      and 2 weeks post-inoculation. RESULTS: The in vitro study revealed robust biofilm
      formation by S. pneumoniae after 12-18 hours of incubation in high glucose
      medium, independent of exogenously supplied competence stimulating peptide and
      medium replacement. Adherent cells formed three-dimensional structures
      approximately 20-30 um thick. The in vivo study revealed that ciliated epithelium
      was relatively resistant to biofilm formation and that biofilm formation occurred
      mainly on non-ciliated epithelium of the middle ear cavity. One week after
      inoculation, biofilm formation was high in 50% of the treated rats and low in 25%
      of the rats. After 2 weeks, biofilm formation was high and low in 25% and 37.5%
      of rats, respectively. CONCLUSION: The results imply that glucose level is
      important for the S. pneumoniae biofilm formation and S. pneumoniae biofilm
      formation may play important role in the pathophysiology of OM.

PMID- 22977711
TI  - Are systemic voriconazole and caspofungin ototoxic? An experimental study with
      rats.
AB  - OBJECTIVES: To determine whether systemic administration of voriconazole and
      caspofungin causes ototoxicity. METHODS: This study was conducted on 32 healthy
      male Wistar albino rats. The baseline auditory brainstem response (ABR)
      thresholds of all animals were obtained under general anesthesia. Then, the rats
      were randomly divided into 4 groups (groups I-IV), each group consisting of 8
      rats. Rats in group I were injected intraperitoneally with voriconazole 10
      mg/kg/day for 7 days, and the rats in the group II were injected
      intraperitoneally with caspofungin 5 mg/kg/day for 7 days. Group III received 120
      mg/kg/day gentamicin for 7 days. Group IV received saline for 7 days. The animals
      were then observed for 7 days, and on 14th day of the trial, posttreatment ABRs
      of both ears were recorded. RESULTS: We did not find any significant differences
      between pretreatment and posttreatment median ABR thresholds in the voriconazole,
      caspofungin, or saline groups. In the gentamicin group, there was a statistically
      significant difference between pretreatment and posttreatment ABR thresholds.
      CONCLUSION: Caspofungin and voriconazole did not change ABR thresholds in speech
      frequencies after a 7-day-period of their administration. We believe that further
      animal studies must be performed after administration of these agents for a
      longer time period, and these findings must be consolidated with
      histopathological investigations.

PMID- 22977712
TI  - Relationships between Lymph Node Metastasis and Expression of CD31, D2-40, and
      Vascular Endothelial Growth Factors A and C in Papillary Thyroid Cancer.
AB  - OBJECTIVES: To investigate the relationships between lymph node metastasis (LNM)
      and expression of CD31, D2-40 and vascular endothelial growth factors (VEGF)-A
      and -C in patients with papillary thyroid cancer (PTC). METHODS: Paraffin
      embedded thyroid tissues of 72 patients were evaluated, which included 25
      patients with thyroid nodular hyperplasia (TNH), 24 PTC patients without LNM, and
      23 PTC patients with LNM. Three pathologists, who were blinded to the patient's
      clinical information, assessed the immunohistochemical staining results. The
      amount of expression was scored as high (>25% of cells stained) or low (0-25%).
      RESULTS: A higher level of VEGF-A expression was observed in the PTC groups
      regardless of LNM when compared to the group with TNH (91.3%, 79.2%, 4.0%,
      respectively). VEGF-C expression in the PTC with LNM group was significantly
      higher than the other two groups (P<0.05). No difference in microvessel density
      (MVD) scores was observed using CD31 among the three groups. The lymphatic vessel
      density (LVD) score using D2-40 was significantly higher in patients having PTC
      with LNM than the other groups (P<0.05). CONCLUSION: VEGF-C and D2-40 were more
      highly expressed in patients having PTC with LNM than in patients having PTC
      without LNM or in those having TNH. Analysis of VEGF-C level and LVD using D2-40
      may be helpful in the diagnosis of PTC and the evaluation of LNM potential in
      patients with PTC.

PMID- 22977713
TI  - Intersession repeatability of acoustic rhinometry measurements in healthy
      volunteers.
AB  - OBJECTIVES: Acoustic rhinometry is a rapid, reliable and non-invasive technique
      for the evaluation of conditions associated with impaired nasal patency. This
      study aimed to examine the intersession repeatability of acoustic rhinometry
      measurements of unilateral and combined nasal parameters in a group of healthy
      volunteers. METHODS: Twenty healthy volunteers were studied. In each subject,
      acoustic rhinometry measurements were performed on five consecutive days, with
      multiple recordings. Five clinically relevant parameters were measured in each
      session and the intersession repeatability of these measurements was expressed in
      terms of mean coefficient of variation, intraclass correlation coefficient and
      inter-item correlations. RESULTS: Intraclass correlation coefficients showed a
      high, and greater repeatability over time for all the combined (mean) values
      compared to the unilateral values. All intraclass correlations for combined
      values were >=0.80 confirming almost perfect agreement. All intraclass
      correlations and inter-item correlations were associated with P<0.001. The mean
      coefficient of variation was low (<10%) for all but the proximal minimum cross
      sectional area (MCA1) measurements. CONCLUSION: Acoustic rhinometry provides
      highly repeatable measurements of nasal patency, which is best for combined
      (mean) nasal parameters. This property makes it suitable for use in the diagnosis
      and follow-up of conditions associated with nasal obstruction, either structural
      or functional.

PMID- 22977714
TI  - Phorbol 12-Myristate 13-Acetate Induces MUC16 Expression via PKCdelta and p38 in
      Human Airway Epithelial Cells.
AB  - OBJECTIVES: Phorbol 12-myristate 13-acetate (PMA) is widely used as a protein
      kinase C (PKC) activator, PKC is involved in the secretion of mucins. MUC16, one
      of the membrane-bound mucins, is produced in human airway epithelial cells.
      However, the effect and signaling pathway of PMA on MUC16 expression in human
      airway epithelial cells has not been reported. Therefore, the effect and brief
      signaling pathway of PMA on MUC16 expression were investigated in human airway
      epithelial cells in this study. METHODS: In the mucin-producing human NCI-H292
      airway epithelial cells and the primary cultures of normal nasal epithelial
      cells, the effect and signaling pathway of PMA on MUC16 expression were
      investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real
      time PCR, enzyme immunoassay, and immunoblot analysis with several specific
      inhibitors and small interfering RNA (siRNA) for p38 mitogen-activated protein
      kinase (MAPK). RESULTS: PMA increased MUC16 expression, and activated
      phosphorylation of p38 MAPK. However, it did not activate phosphorylation of
      extracellular signal-regulated kinase 1/2 (ERK1/2). SB203580 (p38 MAPK inhibitor)
      inhibited PMA-induced MUC16 expression, while U0126 (ERK1/2 inhibitor) did not.
      In addition, the knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked
      PMA-induced MUC16 mRNA expression. Rottlerin (PKCdelta inhibitor) inhibited PMA
      induced MUC16 expression, and also inhibited the phosphorylation of activated p38
      MAPK by PMA. CONCLUSION: These results show for the first time that PMA-induced
      MUC16 expression is regulated by activation of the PKCdelta and p38 MAPK
      signaling pathway in human airway epithelial cells.

PMID- 22977715
TI  - Pulsatile tinnitus as the sole manifestation of an internal carotid artery
      aneurysm successfully treated by coil embolization.
AB  - Pulsatile tinnitus is tinnitus that coincides with the patient's heartbeat. It
      constitutes a small portion of all tinnitus, but it is often the first or sole
      manifestation of a serious disease in the nervous system. Aneurysm of the
      internal carotid artery is known as a rare cause of pulsatile tinnitus and, in
      the main, aneurysms of the petrous portion have been reported as a cause of
      pulsatile tinnitus. We present an interesting case of pulsatile tinnitus that was
      caused by a paraclinoid aneurysm in this report and discuss clinical features and
      treatment of paraclinoid aneurysm.

PMID- 22977716
TI  - Nasal hemangiopericytoma causing oncogenic osteomalacia.
AB  - Oncogenic osteomalacia is a rare cause that makes abnormalities of bone
      metabolism. Our case arose in a 47-year-old woman presenting a nasal mass
      associated with osteomalacia. We excised the mass carefully. After surgery, it
      was diagnosed as hemangiopericytoma and her symptoms related with osteomalacia
      were relieved and biochemical abnormalities were restored to normal range. We
      report and review a rare case of nasal hemangiopericytoma that caused
      osteomalacia.

PMID- 22977717
TI  - Complete laryngotracheal separation following attempted hanging.
AB  - Laryngotracheal separation (LTS) is the most immediately life-threatening airway
      injury. LTS is so rare that very few otolaryngologists have experience with it.
      LTS is one of the diagnostic and therapeutic challenges in airway diseases and
      its management remains to be established. We experienced a patient with complete
      LTS after attempted hanging. A high index of suspicion, adequate imaging, prompt
      airway establishment and early surgical repair are the most vital factors in
      managing a patient with LTS.

PMID- 22977718
TI  - Evaluation of bonding efficiency between facial silicone and acrylic resin using
      different bonding agents and surface alterations.
AB  - PURPOSE: The aim of the study was to evaluate the effect of 3 silicone primers
      and 3 surface characterization of acrylic resin surface on bond strength between
      silicone elastomer and acrylic resin. MATERIALS AND METHODS: 96 Cosmesil
      silicones bonded to heat-curing acrylic resin were fabricated with the dimension
      of 75 * 10 * 3 mm. The 3 primers used in this study were G611 platinum primer, A
      330 Gold platinum primer, and cyanoacrylates resin. Specimens without primer were
      used as control. The 3 types of surface characterization done were retentive
      holes with 1.5 mm in diameter and 0.5 mm deep, retentive beads of 0.6 mm diameter
      and the third type which was plain without any characterization. The specimens
      were then checked for bond strength by subjecting them to 180 degrees  peel test
      on a universal testing machine. The obtained results were then subjected to
      statistical analysis using 2-way ANOVA and Scheffe multiple post hoc procedures.
      The statistical significance was set at 5% level of significance. RESULTS: The
      maximum bond strength was seen for samples in which A-330G primer was used
      followed by G611 primer. The control group showed the minimum bond strength.
      Surface characterization of retentive holes increased the bond strength
      considerably as compared to retentive beads and samples without any surface
      characterization. CONCLUSION: Within the limitations of the study, A-330G primer
      was more compatible with Cosmesil M511 silicone and has better bonding of
      Cosmesil to acrylic resin. Retentive holes made on acrylic surface increased the
      bond strength considerably than those without any surface characterization.

PMID- 22977719
TI  - Comparison of effect of desensitizing agents on the retention of crowns cemented
      with luting agents: an in vitro study.
AB  - PURPOSE: Many dentists use desensitizing agents to prevent hypersensitivity. This
      study compared and evaluated the effect of two desensitizing agents on the
      retention of cast crowns when cemented with various luting agents. MATERIALS AND
      METHODS: Ninety freshly extracted human molars were prepared with flat occlusal
      surface, 6 degree taper and approximately 4 mm axial length. The prepared
      specimens were divided into 3 groups and each group is further divided into 3
      subgroups. Desensitizing agents used were GC Tooth Mousse and GLUMA(r)
      desensitizer. Cementing agents used were zinc phosphate, glass ionomer and resin
      modified glass ionomer cement. Individual crowns with loop were made from base
      metal alloy. Desensitizing agents were applied before cementation of crowns
      except for control group. Under tensional force the crowns were removed using an
      automated universal testing machine. Statistical analysis included one-way ANOVA
      followed by Turkey-Kramer post hoc test at a preset alpha of 0.05. RESULTS: Resin
      modified glass ionomer cement exhibited the highest retentive strength and all
      dentin treatments resulted in significantly different retentive values (In Kg.):
      GLUMA (49.02 +/- 3.32) > Control (48.61 +/- 3.54) > Tooth mousse (48.34 +/-
      2.94). Retentive strength for glass ionomer cement were GLUMA (41.14 +/- 2.42) >
      Tooth mousse (40.32 +/- 3.89) > Control (39.09 +/- 2.80). For zinc phosphate
      cement the retentive strength were lowest GLUMA (27.92 +/- 3.20) > Control (27.69
      +/- 3.39) > Tooth mousse (25.27 +/- 4.60). CONCLUSION: The use of GLUMA(r)
      desensitizer has no effect on crown retention. GC Tooth Mousse does not affect
      the retentive ability of glass ionomer and resin modified glass ionomer cement,
      but it decreases the retentive ability of zinc phosphate cement.

PMID- 22977720
TI  - Short-term evaluation of dental implants in a diabetic population: an in vivo
      study.
AB  - PURPOSE: The study was conducted to evaluate the efficacy of implant supported
      tooth replacement in diabetic patients. MATERIALS AND METHODS: The study involved
      placement of implants (UNITI implants, Equinox Medical Technologies, Zeist,
      Holland, diameter of 3.7 mm and length 13 mm) in five diabetic patients (three
      females and two males) of age ranging from 35-65 years with acceptable metabolic
      control of plasma glucose. All patients included in the study were indicated for
      single tooth maxillary central incisor replacement, with the adjacent teeth
      intact. The survival of the restored implants was assessed for a period of three
      months by measurement of crestal bone heights, bleeding on probing and micro
      flora predominance. Paired t-test was done to find out the difference in the
      microbial colonization, bleeding on probing and crestal bone loss. P values of
      less than 0.05 were taken to indicate statistical significance. RESULTS: Results
      indicated that there was a significant reduction in bleeding on probing and
      colonization at the end of three months and the bone loss was not statistically
      significant. CONCLUSION: The study explores the hypothesis that patients with
      diabetes are appropriate candidates for implants and justifies the continued
      evaluation of the impact of diabetes on implant success and complications.

PMID- 22977722
TI  - Cortical and cancellous bone thickness on the anterior region of alveolar bone in
      Korean: a study of dentate human cadavers.
AB  - PURPOSE: The cortical bone thickness on the anterior region is important for
      achieving implant stability. The purpose of this study was to examine the
      thickness of the cortical and cancellous bones on the anterior region of the
      maxilla and mandible. MATERIALS AND METHODS: Twenty-five cadaver heads were used
      (16 male and 9 female; mean death age, 56.7 years). After the long axis of
      alveolar process was set up, it was measured in 5 levels starting from 2 mm below
      the cementoenamel junction (L1) at intervals of 3 mm. All data was analysed
      statistically by one-way ANOVA at the .05 significance level. RESULTS: The
      cortical bone thickness according to measurement levels in both the labial and
      lingual sides increased from L1 to L5, and the lingual side below L3 was
      significantly thicker than the labial side on the maxilla and mandible. In
      particular, the labial cortical bone thickness in the maxilla was the thinnest
      compared to the other regions. The cancellous bone thickness according to
      measurement levels increased from L1 to L5 on the maxilla, and on the mandible it
      was the thinnest at the middle level of the root. CONCLUSION: For implant
      placement on the anterior region, a careful evaluation and full knowledge on the
      thickness of the cortical and cancellous bone are necessary, therefore, these
      results may provide an anatomic guideline to clinicians.

PMID- 22977721
TI  - Efficacy of various cleansing techniques on dentin wettability and its influence
      on shear bond strength of a resin luting agent.
AB  - PURPOSE: To evaluate the shear bond strength of resin luting agent to dentin
      surfaces cleansed with different agents like pumice, ultrasonic scaler with
      chlorhexidine gluconate, EDTA and the influence of these cleansing methods on
      wetting properties of the dentin by Axisymmetric drop Shape Analysis - Contact
      Diameter technique (ADSA-CD). MATERIALS AND METHODS: Forty coronal portions of
      human third molar were prepared until dentin was exposed. Specimens were divided
      into two groups: Group A and Group B. Provisional restorations made with
      autopolymerizing resin were luted to dentin surface with zinc oxide eugenol in
      Group A and with freegenol cement in Group B. All specimens were stored in
      distilled water at room temperature for 24 hrs and provisional cements were
      mechanically removed with explorer and rinsed with water and cleansed using
      various methods (Control-air-water spray, Pumice prophylaxis, Ultrasonic scaler
      with 0.2% Chlorhexidine gluconate, 17% EDTA). Contact angle measurements were
      performed to assess wettability of various cleansing agents using the ADSA-CD
      technique. Bond strength of a resin luting agent bonded to the cleansed surface
      was assessed using Instron testing machine and the mode of failure noted. SEM was
      done to assess the surface cleanliness. Data were statistically analyzed by one
      way analysis of variance with Tukey HSD tests (alpha=.05). RESULTS: Specimens
      treated with EDTA showed the highest shear bond strength and the lowest contact
      angle for both groups. SEM showed that EDTA was the most effective solution to
      remove the smear layer. Also, mode of failure seen was predominantly cohesive for
      both EDTA and pumice prophylaxis. CONCLUSION: EDTA was the most effective dentin
      cleansing agent among the compared groups.

PMID- 22977723
TI  - A comparative study to measure the condylar guidance by the radiographic and
      clinical methods.
AB  - PURPOSE: The study was conducted to compare the radiographic and clinical methods
      of measuring the horizontal condylar guidance (HCG) values. MATERIALS AND
      METHODS: The condylar guidance was measured using the radiographic (CT scan) and
      three clinical methods i.e. the wax protrusive records, Lucia jig record and
      intraoral central bearing device in 12 patients aged between 20-40 years
      irrespective of sex. The records were taken and transferred on the semi
      adjustable articulator to record the HCG values. The CT scan was taken for 3D
      reconstruction of the mid facial region. Frankfort horizontal plane (FHP) and a
      line extending from the superior anterior most point on the glenoid fossa to the
      most convex point on the apex of articular eminence (AE) was marked on the CT
      scan. An angle between these two lines was measured on both right and left sides
      to obtain condylar inclination angle. Three interocclusal protrusive wax and jig
      records were taken and transferred to the semi adjustable articulator. Three
      readings were recorded on each side. Similarly the records were taken and
      transferred to the same articulator using the intra oral central bearing device
      to record the readings. RESULTS: The statistical analysis showed insignificant
      differences in the HCG values between the right and left sides [(P=.589 (CT),
      P=.928 (wax), P=.625 (jig), P=.886 (tracer)]. The clinical methods provided low
      Pearsons correlation values [(R = 0.423 (wax), R = 0.354 (jig), R = 0.265
      (tracer)] for the right as well as the left sides when compared with the CT
      values. Among the clinical methods, jig and wax method showed strong level of
      association which is statistically significant while the intra-oral tracer showed
      weak association with the other two methods. CONCLUSION: The right and left HCG
      values were almost similar. The CT scan showed higher HCG values than the
      clinical methods and among the clinical methods, values obtained from all the
      methods were comparable.

PMID- 22977724
TI  - Mechanical analysis of conventional and small diameter conical implant abutments.
AB  - PURPOSE: The aim of the present study was to evaluate if a smaller morse taper
      abutment has a negative effect on the fracture resistance of implant-abutment
      connections under oblique compressive loads compared to a conventional abutment.
      MATERIALS AND METHODS: Twenty morse taper conventional abutments (4.8 mm
      diameter) and smaller abutments (3.8 mm diameter) were tightened (20 Ncm) to
      their respective implants (3.5 * 11 mm) and after a 10 minute interval,
      implant/abutment assemblies were subjected to static compressive test, performed
      in a universal test machine with 1 mm/min displacement, at 45 degrees 
      inclination. The maximum deformation force was determined. Data were
      statistically analyzed by student t test. RESULTS: Maximum deformation force of
      4.8 mm and 3.8 mm abutments was approximately 95.33 kgf and 95.25 kgf,
      respectively, but no fractures were noted after mechanical test. Statistical
      analysis demonstrated that the evaluated abutments were statistically similar
      (P=.230). CONCLUSION: Abutment measuring 3.8 mm in diameter (reduced) presented
      mechanical properties similar to 4.8 mm (conventional) abutments, enabling its
      clinical use as indicated.

PMID- 22977725
TI  - In vitro evaluation of fracture strength of zirconia restoration veneered with
      various ceramic materials.
AB  - PURPOSE: Fracture of the veneering material of zirconia restorations frequently
      occurs in clinical situations. The purpose of this in vitro study was to compare
      the fracture strengths of zirconia crowns veneered with various ceramic materials
      by various techniques. MATERIALS AND METHODS: A 1.2 mm, 360 degrees  chamfer
      preparation and occlusal reduction of 2 mm were performed on a first mandibular
      molar, and 45 model dies were fabricated in a titanium alloy by CAD/CAM system.
      Forty-five zirconia copings were fabricated and divided into three groups. In the
      first group (LT) zirconia copings were veneered with feldspathic porcelain by the
      layering technique. In the second group (HT) the glass ceramic was heat-pressed
      on the zirconia coping, and for the third group (ST) a CAD/CAM-fabricated high
      strength anatomically shaped veneering cap was sintered onto the zirconia coping.
      All crowns were cemented onto their titanium dies with Rely XTM Unicem (3M ESPE)
      and loaded with a universal testing machine (Instron 5583) until failure. The
      mean fracture values were compared by an one-way ANOVA and a multiple comparison
      post-hoc test (alpha=0.05). Scanning electron microscope was used to investigate
      the fractured interface. RESULTS: Mean fracture load and standard deviation was
      4263.8+/-1110.8 N for Group LT, 5070.8+/-1016.4 for Group HT and 6242.0+/-1759.5
      N for Group ST. The values of Group ST were significantly higher than those of
      the other groups. CONCLUSION: Zirconia crowns veneered with CAD/CAM generated
      glass ceramics by the sintering technique are superior to those veneered with
      feldspathic porcelain by the layering technique or veneered with glass ceramics
      by the heat-pressing technique in terms of fracture strength.

PMID- 22977726
TI  - A simplified chair-side remount technique using customized mounting platforms.
AB  - Correct occlusal relationships are part of the successful prosthetic treatment
      for edentulous patients. Fabrication of complete dentures comprises of clinical
      and laboratory procedures that should be executed accurately for achieving
      success with fabricated dentures. Errors occurring during the clinical and
      laboratory procedures of a denture may subsequently lead to the occlusal errors
      in the final prosthesis. These occlusal errors can be corrected in two ways: i)
      in patient's mouth ii) by recording new centric relation and remounting dentures
      on an articulator. The latter method is more feasible because the mobility of
      denture base on the mucosa in oral cavity does not permit the identification of
      premature contacts in centric occlusion and tooth guided eccentric excursions.
      This article describes a modest and effective clinical chair-side remount
      procedure using customized mounting platforms.

PMID- 22977727
TI  - Improving oral rehabilitation through the preservation of the tissues through
      alveolar preservation.
AB  - When performing a tooth extraction, imminent collapse of the tissue by resorption
      and remodeling of the socket is a natural occurrence. The procedure for the
      preservation of the alveolar ridge has been widely described in the dental
      literatures and aims to maintain hard and soft tissues in the extraction site for
      optimal rehabilitation either with conventional fixed or removable prosthetics or
      implant-supported prosthesis.

PMID- 22977728
TI  - Decline of forest interior conditions in the conterminous United States.
AB  - Forest fragmentation threatens the sustainability of forest interior
      environments, thereby endangering subordinate ecological attributes and
      functions. We analyzed the spatial patterns of forest loss and gain for the
      conterminous United States from 2001 to 2006 to determine whether forest interior
      environments were maintained at five spatial scales. A 1.1% net loss of total
      forest area translated to net losses of 3.2% to 10.5% of forest interior area
      over spatial scales of 4.41 ha to 5,310 ha. At the 65.6-ha scale, the reduction
      of forest interior area was 50,000 km2--almost double the net loss of total
      forest area. The pervasive discrepancy between total forest loss and forest
      interior loss indicates a widespread shift of the extant forest to more
      fragmented conditions, even in regions exhibiting small net changes in extant
      forest area. In the conterminous United States, trends in total forest area
      underestimate threats to forest from forest fragmentation.

PMID- 22977730
TI  - A quantum phase transition in a quantum external field: superposing two magnetic
      phases.
AB  - We study an Ising chain undergoing a quantum phase transition in a quantum
      magnetic field. Such a field can be emulated by coupling the chain to a central
      spin initially in a superposition state. We show that--by adiabatically driving
      such a system--one can prepare a quantum superposition of any two ground states
      of the Ising chain. In particular, one can end up with the Ising chain in a
      superposition of ferromagnetic and paramagnetic phases--a scenario with no
      analogue in prior studies of quantum phase transitions. Remarkably, the resulting
      magnetization of the chain encodes the position of the critical point and
      universal critical exponents, as well as the ground state fidelity.

PMID- 22977729
TI  - Stable isotope analysis challenges wasp-waist food web assumptions in an
      upwelling pelagic ecosystem.
AB  - Eastern boundary currents are often described as 'wasp-waist' ecosystems in which
      one or few mid-level forage species support a high diversity of larger predators
      that are highly susceptible to fluctuations in prey biomass. The assumption of
      wasp-waist control has not been empirically tested in all such ecosystems. This
      study used stable isotope analysis to test the hypothesis of wasp-waist control
      in the southern California Current large marine ecosystem (CCLME). We analyzed
      prey and predator tissue for delta13C and delta15N and used Bayesian mixing
      models to provide estimates of CCLME trophic dynamics from 2007-2010. Our results
      show high omnivory, planktivory by some predators, and a higher degree of trophic
      connectivity than that suggested by the wasp-waist model. Based on this study
      period, wasp-waist models oversimplify trophic dynamics within the CCLME and
      potentially other upwelling, pelagic ecosystems. Higher trophic connectivity in
      the CCLME likely increases ecosystem stability and resilience to perturbations.

PMID- 22977731
TI  - The cell cycle switch computes approximate majority.
AB  - Both computational and biological systems have to make decisions about switching
      from one state to another. The 'Approximate Majority' computational algorithm
      provides the asymptotically fastest way to reach a common decision by all members
      of a population between two possible outcomes, where the decision approximately
      matches the initial relative majority. The network that regulates the mitotic
      entry of the cell-cycle in eukaryotes also makes a decision before it induces
      early mitotic processes. Here we show that the switch from inactive to active
      forms of the mitosis promoting Cyclin Dependent Kinases is driven by a system
      that is related to both the structure and the dynamics of the Approximate
      Majority computation. We investigate the behavior of these two switches by
      deterministic, stochastic and probabilistic methods and show that the steady
      states and temporal dynamics of the two systems are similar and they are
      exchangeable as components of oscillatory networks.

PMID- 22977732
TI  - Crystal structure of folliculin reveals a hidDENN function in genetically
      inherited renal cancer.
AB  - Mutations in the renal tumour suppressor protein, folliculin, lead to
      proliferative skin lesions, lung complications and renal cell carcinoma.
      Folliculin has been reported to interact with AMP-activated kinase, a key
      component of the mammalian target of rapamycin pathway. Most cancer-causing
      mutations lead to a carboxy-terminal truncation of folliculin, pointing to a
      functional importance of this domain in tumour suppression. We present here the
      crystal structure of folliculin carboxy-terminal domain and demonstrate that it
      is distantly related to differentially expressed in normal cells and neoplasia
      (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors
      (GEFs). Using biochemical analysis, we show that folliculin has GEF activity,
      indicating that folliculin is probably a distantly related member of this class
      of Rab GEFs.

PMID- 22977733
TI  - The Saccharomyces cerevisiae W303-K6001 cross-platform genome sequence: insights
      into ancestry and physiology of a laboratory mutt.
AB  - Saccharomyces cerevisiae strain W303 is a widely used model organism. However,
      little is known about its genetic origins, as it was created in the 1970s from
      crossing yeast strains of uncertain genealogy. To obtain insights into its
      ancestry and physiology, we sequenced the genome of its variant W303-K6001, a
      yeast model of ageing research. The combination of two next-generation sequencing
      (NGS) technologies (Illumina and Roche/454 sequencing) yielded an 11.8 Mb genome
      assembly at an N50 contig length of 262 kb. Although sequencing was substantially
      more precise and sensitive than whole-genome tiling arrays, both NGS platforms
      produced a number of false positives. At a 378* average coverage, only 74 per
      cent of called differences to the S288c reference genome were confirmed by both
      techniques. The consensus W303-K6001 genome differs in 8133 positions from S288c,
      predicting altered amino acid sequence in 799 proteins, including factors of
      ageing and stress resistance. The W303-K6001 (85.4%) genome is virtually
      identical (less than equal to 0.5 variations per kb) to S288c, and thus
      originates in the same ancestor. Non-S288c regions distribute unequally over the
      genome, with chromosome XVI the most (99.6%) and chromosome XI the least (54.5%)
      S288c-like. Several of these clusters are shared with Sigma1278B, another widely
      used S288c-related model, indicating that these strains share a second ancestor.
      Thus, the W303-K6001 genome pictures details of complex genetic relationships
      between the model strains that date back to the early days of experimental yeast
      genetics. Moreover, this study underlines the necessity of combining multiple NGS
      and genome-assembling techniques for achieving accurate variant calling in
      genomic studies.

PMID- 22977734
TI  - Adult lung stem cells and their contribution to lung tumourigenesis.
AB  - The isolation and characterization of lung stem and progenitor cells represent an
      important step towards the understanding of lung repair after injury, lung
      disease pathogenesis and the identification of the target cells of transformation
      in lung carcinogenesis. Different approaches using prospective isolation of
      progenitor cells by flow cytometry or lineage-tracing experiments in mouse models
      of lung injury have led to the identification of distinct progenitor
      subpopulations in different morphological regions of the adult lung. Genetically
      defined mouse models of lung cancer are offering new perspectives on the cells of
      origin of different subtypes of lung cancer. These mouse models pave the way to
      further investigate human lung progenitor cells at the origin of lung cancers, as
      well as to define the nature of the lung cancer stem cells. It will be critical
      to establish the link between oncogenic driver mutations recently discovered in
      lung cancers, target cells of transformation and subtypes of lung cancers to
      enable better stratification of patients for improved therapeutic strategies.

PMID- 22977735
TI  - On the inscrutable role of Inscuteable: structural basis and functional
      implications for the competitive binding of NuMA and Inscuteable to LGN.
AB  - Alignment of the mitotic spindle to the cellular polarity axis is a prerequisite
      for asymmetric cell divisions. The protein network coordinating the spindle
      position with cortical polarity includes the molecular machinery pulling on
      astral microtubules, which is assembled on conserved NuMA:LGN:Galphai complexes,
      the polarity proteins Par3:Par6:aPKC and an adaptor molecule known as Inscuteable
      (Insc). To date, all these components were assumed to enter a macromolecular
      complex localized at polarity sites in mitosis. However, recent structural
      studies revealed the Insc and NuMA are mutually exclusive interactors of LGN,
      implying that the molecular mechanism of spindle coupling to polarity is more
      sophisticated than has been believed to date.

PMID- 22977737
TI  - Association Between Earlobe Crease and the Metabolic Syndrome in a Cross
      sectional Study.
AB  - OBJECTIVES: Several studies found a significant association between earlobe
      crease (ELC) and cardiovascular disease (CVD). Metabolic syndrome (MS) is a group
      of high-risk factors that are a collection of cardiovascular risk factors. Scant
      data are available about the relationship between ELC and MS. The purpose of the
      current study was to examine the correlation between ELC and MS. METHODS: A cross
      sectional study was performed on 3,835 subjects (1,672 females, 43.6%) aged 20 to
      79 years who visited a health promotion center. To increase the reliability of
      the diagnosis of MS, both the modified National Cholesterol Education Program
      Adult Treatment Panel III (NCEP ATP III) and International Diabetes Federation
      (IDF) criteria were applied. Independent association between ELC and MS was
      assessed using multiple logistic regression analysis after adjusting for
      confounding variables. RESULTS: The frequency of ELC was 20.89% and the
      prevalence of MS was 11.03% (NCEP criteria) and 9.75% (IDF criteria). The
      prevalence of both ELC and MS significantly increased with age. The modified
      Framingham risk score was significantly higher in subjects with ELC than without.
      After adjusting for conventional risk factors for CVD, the risk of MS increased
      significantly in the presence of ELC. CONCLUSION: The current study showed that
      the odds ratio for MS increased in the presence of ELC in Korean adults. ELC is
      an auxiliary indicator of MS, although prognostic value might be limited. Further
      studies are warranted to elucidate the clinical significance of ELC.

PMID- 22977736
TI  - Structured illumination of the interface between centriole and peri-centriolar
      material.
AB  - The increase in centrosome size in mitosis was described over a century ago, and
      yet it is poorly understood how centrioles, which lie at the core of centrosomes,
      organize the pericentriolar material (PCM) in this process. Now, structured
      illumination microscopy reveals in Drosophila that, before clouds of PCM appear,
      its proteins are closely associated with interphase centrioles in two tube-like
      layers: an inner layer occupied by centriolar microtubules, Sas-4, Spd-2 and Polo
      kinase; and an outer layer comprising Pericentrin-like protein (Dplp), Asterless
      (Asl) and Plk4 kinase. Centrosomin (Cnn) and gamma-tubulin associate with this
      outer tube in G2 cells and, upon mitotic entry, Polo activity is required to
      recruit them together with Spd-2 into PCM clouds. Cnn is required for Spd-2 to
      expand into the PCM during this maturation process but can itself contribute to
      PCM independently of Spd-2. By contrast, the centrioles of spermatocytes elongate
      from a pre-existing proximal unit during the G2 preceding meiosis. Sas-4 is
      restricted to the microtubule-associated, inner cylinder and Dplp and Cnn to the
      outer cylinder of this proximal part. gamma-Tubulin and Asl associate with the
      outer cylinder and Spd-2 with the inner cylinder throughout the entire G2
      centriole. Although they occupy different spatial compartments on the G2
      centriole, Cnn, Spd-2 and gamma-tubulin become diminished at the centriole upon
      entry into meiosis to become part of PCM clouds.

PMID- 22977738
TI  - The Burden of Premature Mortality in Hamadan Province in 2006 and 2010 Using
      Standard Expected Years of Potential Life Lost: A Population-based Study.
AB  - OBJECTIVES: Examining the premature death rate represents the first step in
      estimating the overall burden of disease, reflecting a full picture of how
      different causes affect population health and providing a way of monitoring and
      evaluating population health. The present study was conducted to assess the
      burden of premature mortality in Hamadan Province, Iran in 2006 and 2010.
      METHODS: To calculate years of potential life lost (YPLL), the dataset was
      categorized into 5-year age groups based on each person's age at death. Then the
      age groups were subtracted from the relevant age-based life table produced by the
      World Health Organization in 2009. The YPLL for each individual were then added
      together to yield the total YPLL for all individuals in the population who died
      in a particular year. Finally, we calculated the YPLL for all sex-, age-, and
      cause-specific mortality rates and reported them as percentages. RESULTS: We
      analyzed 18,786 deaths, 9,127 of which occurred in 2006 and 9,659 in 2010.
      Mortality rates were higher in men than women for all age groups both in 2006 and
      2010. In addition, age-specific mortality rates in both genders for all age
      groups were higher in 2010 than in 2006. The percentage of YPLL from ischemic
      heart diseases, cerebrovascular diseases, transport accidents, and intentional
      self-harm were among the greatest sources of premature death. CONCLUSION: The
      results of the present survey indicate that the eight major causes of premature
      death in both 2006 and 2010 were non-communicable diseases, especially ischemic
      heart diseases, cerebrovascular diseases, transport accidents, and intentional
      self-harm. Furthermore, our findings indicate a change in the role of non
      communicable diseases in premature mortality in recent years.

PMID- 22977739
TI  - Smart copying.

PMID- 22977740
TI  - The biological effects of fibrin-binding synthetic oligopeptides derived from
      fibronectin on osteoblast-like cells.
AB  - PURPOSE: The aim of this study was to investigate the effects of synthetic
      fibronectin (FN) fragments, including fibrin binding sites from amino-terminal FN
      fragments containing type I repeats 1 to 5, on osteoblast-like cell activity.
      METHODS: Oligopeptides ranging from 9 to 20 amino acids, designated FF1, FF3, and
      FF5, were synthesized by a solid-phase peptide synthesizing system, and we
      investigated the effects of these peptides on cell attachment and extent of
      mineralization using confocal microscopy, 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays, and Alizarin red S staining. RESULTS: FF3 and
      FF5 peptides increased the number of attached human osteoblastic cells, and FF3
      administration led to prominent cell spreading. Mineralization was increased in
      FF3 and FF5 compared to FF1 and the untreated control. CONCLUSIONS: Taken
      together, it can be concluded that the fibrin-binding oligopeptides FF3 and FF5
      enhanced cell attachment and mineralization on osteoblast-like cells. These
      results indicate that FF3 and FF5 have the potential to increase osteoblast-like
      cell activity. Performing an in vivo study may provide further possibilities for
      surface modification of biomimetic peptides to enhance osteogenesis, thus
      improving the regeneration of destroyed alveolar bone.

PMID- 22977741
TI  - Improvement of osteogenic potential of biphasic calcium phosphate bone substitute
      coated with two concentrations of expressed recombinant human bone morphogenetic
      protein 2.
AB  - PURPOSE: The aim of this study was to determine whether biphasic calcium
      phosphate (BCP) bone substitute with two different concentrations of Escherichia
      coli-expressed recombinant human bone morphogenetic protein 2 (ErhBMP-2) enhances
      new bone formation in a standardized rabbit sinus model and to evaluate the
      concentration-dependent effect of ErhBMP-2. METHODS: Standardized, 6-mm diameter
      defects were made bilaterally on the maxillary sinus of 20 male New Zealand white
      rabbits. Following removal of the circular bony windows and reflection of the
      sinus membrane, BCP bone substitute without coating (control group) was applied
      into one defect and BCP bone substitute coated with ErhBMP-2 (experimental group)
      was applied into the other defect for each rabbit. The experimental group was
      divided into 2 subgroups according to the concentration of ErhBMP-2 (0.05 and 0.5
      mg/mL). The animals were allowed to heal for either 4 or 8 weeks and sections of
      the augmented sinus and surrounding bone were analyzed by microcomputed
      tomography and histologically. RESULTS: Histologic analysis revealed signs of new
      bone formation in both the control and experimental groups with a statistically
      significant increase in bone formation in experimental group 1 (0.05 mg/mL ErhBMP
      2 coating) after a 4-week healing period. However, no statistically significant
      difference was found between experimental group 1 and experimental group 2 (0.5
      mg/mL ErhBMP-2 coating) in osteoinductive potential (P<0.05). CONCLUSIONS: ErhBMP
      2 administered using a BCP matrix significantly enhanced osteoinductive potential
      in a standardized rabbit sinus model. A concentration-dependent response was not
      found in the present study.

PMID- 22977742
TI  - Clinical evaluation of a biphasic calcium phosphate grafting material in the
      treatment of human periodontal intrabony defects.
AB  - PURPOSE: The aim of this study was to compare the clinical outcome of open flap
      debridement (OFD) with a biphasic calcium phosphate (BCP) graft to that of OFD
      without BCP graft for the treatment of intrabony periodontal defects (IBDs).
      METHODS: The study included 25 subjects that had at least one intrabony defect of
      2- or 3-wall morphology and an intrabony component>=4 mm as detected
      radiographically. Subjects were randomly assigned to treatment with (BCP group,
      n=14) or without BCP (OFD group, n=11). Clinical parameters were recorded at
      baseline and 6 months after surgery and included the plaque index, gingival
      index, probing depth (PD), clinical attachment level (CAL), and gingival
      recession (REC). A stringent plaque control regimen was enforced for all of the
      patients during the 6-month observation period. RESULTS: In all of the treatment
      groups, significant PD reductions and CAL gains occurred during the study period
      (P<0.01). At 6 months, patients in the BCP group exhibited a mean PD reduction of
      3.7+/-1.2 mm and a mean CAL gain of 3.0+/-1.1 mm compared to the baseline.
      Corresponding values for the patients treated with OFD were 2.5+/-0.8 mm and
      1.4+/-1.0 mm, respectively. Compared to OFD group, the additional CAL gain was
      significantly greater in the patients in BCP group (P=0.028). The additional PD
      reduction was significant for the BCP group (P=0.048). The REC showed a
      significant increase in both groups, and the amount of recession was
      significantly smaller in the BCP group than OFD group (P=0.023). In radiographic
      evaluation, the height of the bone fill in the BCP group was significantly
      greater than OFD group. CONCLUSIONS: The clinical benefits of BCP found in this
      study indicate that BCP may be an appropriate alternative to conventional graft
      materials.

PMID- 22977743
TI  - Novel analysis model for implant osseointegration using ectopic bone formation
      via the recombinant human bone morphogenetic protein-2/macroporous biphasic
      calcium phosphate block system in rats: a proof-of-concept study.
AB  - PURPOSE: The osseointegration around titanium mini-implants installed in
      macroporous biphasic calcium phosphate (MBCP) blocks was evaluated after
      incubation with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an
      ectopic subcutaneous rat model. METHODS: Mini-implants (phi1.8*12 mm) were
      installed in MBCP blocks (bMBCPs, 4*5*15 mm) loaded with rhBMP-2 at 0.1 mg/mL,
      and then implanted for 8 weeks into subcutaneous pockets of male Sprague-Dawley
      rats (n=10). A histomorphometric analysis was performed, and the bone-to-implant
      contact (BIC) and bone density were evaluated. RESULTS: Significant
      osteoinductive activity was induced in the rhBMP-2/bMBCP group. The percentage of
      BIC was 41.23+/-4.13% (mean+/-standard deviation), while bone density was 33.47+/
      5.73%. In contrast, no bone formation was observed in the bMBCP only group.
      CONCLUSIONS: This model represents a more standardized tool for analyzing
      osseointegration and bone healing along the implant surface and in bMBCPs that
      excludes various healing factors derived from selected animals and defect models.

PMID- 22977744
TI  - Commentary on "Reliability of two different presurgical preparation methods for
      implant dentistry based on panoramic radiography and cone-beam computed
      tomography in cadavers".

PMID- 22977745
TI  - Reply on "Reliability of two different presurgical preparation methods for
      implant dentistry based on panoramic radiography and cone-beam computed
      tomography in cadavers".

PMID- 22977748
TI  - Clinicopathological features of female gastric carcinoma patients with curative
      resection: comparison with male patients.
AB  - Little is known about the clinicopathological features of female gastric
      carcinoma (FGC) patients. We compared the clinicopathologic features and outcomes
      of FGC patients with curative resection with those of male gastric carcinoma
      (MGC) patients. We reviewed the hospital records of 940 FGC patients between 1986
      and 2005 at Chonnam National University Hospital. Multivariate analysis showed
      that presence of serosal invasion, lymph node metastasis, and operative type were
      significant prognostic factors for survival of FGC patients with curative
      resection. Furthermore, the overall 5-year survival rate of FGC patients with
      curative resection (53.4%) was higher than that of MGC patients (47.6%, p<0.05).
      In advanced cases, no significant difference was observed in the overall 5-year
      survival rate between the FGC and MGC patients (41.6% vs 37.4%, p>0.05).
      Therefore, serosal invasion, lymph node metastasis, and type of operation were
      statistically significant parameters associated with survival. Early detection is
      more important for improving the prognosis of female patients with gastric cancer
      than for male patients.

PMID- 22977747
TI  - Cysteinyl cathepsins: multifunctional enzymes in cardiovascular disease.
AB  - Until recently, the role of lysosomal cysteine protease cathepsins in
      intracellular protein degradation was believed to be mainly restricted to
      scavenging. However, recent studies have revealed nontraditional roles for
      cysteine protease cathepsins in the extracellular space during the development
      and progression of cardiovascular disease. Although the precise mechanisms are
      unknown, data from animal studies suggest that members of the cathepsin family,
      like other extracellular proteases, contribute to extracellular matrix protein
      remodeling and interstitial matrix degradation, as well as to cell signaling and
      cell apoptosis in heart disease. Inflammatory cytokines and hormones regulate the
      expression and secretion of cathepsins in cultured cardiovascular cells and
      macrophages. Serum levels of cathepsins L, S, and K and their endogenous
      inhibitor cystatin C may be useful predictive biomarkers in patients with
      coronary artery disease and cardiac disease. Furthermore, in vivo pharmacological
      intervention with a synthetic cathepsin inhibitor and cardiovascular drugs
      (including statins and angiotensin II type 1 receptor antagonists) has the
      potential for pharmacologic targeting of cathepsins in cardiovascular disease.
      This review focuses on cathepsin biology (structure, synthesis, processing,
      activation, secretion, activity regulation, and function) and the involvement of
      cysteinyl cathepsins in the pathogenesis of several heart and vessel diseases,
      especially with respect to their potential application as diagnostic and
      prognostic markers and drug targets to prevent inappropriate proteolysis in
      cardiovascular disease.

PMID- 22977749
TI  - Nosocomial Pseudomonas putida Bacteremia: High Rates of Carbapenem Resistance and
      Mortality.
AB  - Previously, Pseudomonas putida was considered a low-virulence pathogen and was
      recognized as a rare cause of bacteremia. Recently, however, multidrug-resistant
      and carbapenem-resistant P. putida isolates have emerged, causing difficult-to
      treat nosocomial infections in seriously ill patients. Currently, the outcome of
      multidrug-resistant or carbapenem-resistant P. putida bacteremia remains
      uncertain. Here, we report 18 cases of P. putida bacteremia with high rates of
      carbapenem resistance and mortality. From January 2005 through December 2011, all
      cases of nosocomial P. putida bacteremia were identified and analyzed at Chonnam
      National University Hospital and Chonnam National University Hwasun Hospital.
      Electronic medical records were reviewed retrospectively. Four (22%) and five
      (23%) of 18 P. putida isolates were resistant to imipenem and meropenem,
      respectively. Common primary infection sites were central venous catheter (7,
      39%), pneumonia (5, 28%), and cholangitis (2, 11%). Fourteen (78%) patients had
      indwelling devices related to the primary site of infection. The 30-day mortality
      rate was 39% (7/18): 40% (2/5) in patients with carbapenem-resistant P. putida
      bacteremia vs. 38% (5/13) in patients with carbapenem-susceptible P. putida
      bacteremia. Nosocomial P. putida bacteremia showed high resistance rates to most
      potent beta-lactams and carbapenems and was associated with high mortality rates.

PMID- 22977750
TI  - Effects on Intubating Conditions of Pretreatment with Remifentanil before
      Administration of Cisatracurium.
AB  - Cisatracurium provides superior hemodynamic stability with only minor release of
      histamine, and its metabolism via Hoffman elimination is independent of organ
      function. However, use of cisatracurium is limited because of reportedly slower
      onset and unsatisfactory intubating conditions. Many studies have shown that
      remifentanil might provide reliable intubating conditions; thus, we hypothesized
      that pretreatment with remifentanil before administration of cisatracurium might
      result in acceptable intubating conditions. Sixty healthy patients scheduled for
      elective surgery were enrolled and randomly divided into three groups: saline
      (Group I, n=20), remifentanil 0.5 ug/kg (Group II, n=20), and remifentanil 1.0
      ug/kg (Group III, n=20). The anesthesia was induced with propofol 2.0 ug/kg given
      intravenously over 30 s followed by injection over 30 s of a different dose of
      remifentanil according to the study protocol. We examined the intubating
      condition by jaw relaxation, vocal cord state, and diaphragmatic response 90 s
      after administering cisatracurium. We also measured mean blood pressure, heart
      rate, and the onset time, which is the interval from the end of neuromuscular
      blocking agent administration until suppression of maximal T1 on a train-of four
      sequence. The mean values of the intubating condition after endotracheal
      intubation in Groups II and III were significantly lower than that in Group I
      (p<0.005), although the overall onset time of cisatracurium did not differ
      significantly between the three groups. Our results suggest that supplementation
      with remifentanil in an induction regimen with cisatracurium improves the quality
      of the intubating condition even though the onset time of cisatracurium is not
      shortened.

PMID- 22977751
TI  - Percutaneous nephrolithotomy in patients on chronic anticoagulant/antiplatelet
      therapy.
AB  - Percutaneous nephrolithotomy (PCNL) is an integral component in the management of
      large volume renal stone disease either as monotherapy or in combination with
      shock wave lithotripsy. Stone disease in patients on chronic
      anticoagulation/antiplatelet therapy, however, poses a difficult scenario.
      Bleeding is a major concern for any patient undergoing PCNL. We retrospectively
      analyzed our series of patients with renal calculi who were on chronic
      anticoagulant therapy and who underwent PCNL. We reviewed the case records of
      patients undergoing PCNL during the period from January 2005 to December 2011. We
      analyzed the changes in preoperative and postoperative hemoglobin, serum
      creatinine, and clotting parameters, as well as intraoperative and postoperative
      bleeding and thromboembolic complications. During the 5-year study period, a
      total of 36 patients (30 males and 6 females) with a mean age of 46.33+/-9.96
      years (range, 29-61 years) who were on chronic anticoagulant/antiplatelet therapy
      underwent PCNL for urolithiasis. The mean size of the stone was 6.40+/-1.98 cm(2)
      (range, 2.8-9 cm(2)). The mean operating time was 62.08+/-10.10 min. The bleeding
      was successfully managed in all patients and the anticoagulant/antiplatelet
      agents were restarted after an appropriate duration. The mean rise in serum
      creatinine at discharge was 0.05+/-0.03 mg/dl and the mean fall in serum
      hemoglobin was 1.63+/-0.77 g/dl. At 3 months after surgery, the stone-free rate
      was 100%. With careful preoperative care and regulation of
      anticoagulation/antiplatelet therapy and appropriate intraoperative management,
      PCNL can be performed safely and successfully in properly selected patients with
      renal calculi who are on chronic anticoagulant/antiplatelet therapy.

PMID- 22977752
TI  - Serum vitamin d status and its relationship to metabolic parameters in patients
      with type 2 diabetes mellitus.
AB  - The potential relationship between vitamin D (VitD) status and metabolic control
      in patients with type 2 diabetes mellitus (T2DM) warrants further study. We aimed
      to evaluate the relationship between the serum 25-hydroxyvitamin D [25(OH)D]
      level and various parameters in patients with T2DM. We analyzed retrospectively
      data from 276 Korean patients with T2DM whose serum 25(OH)D level was measured in
      our hospital. Nondiabetic healthy subjects who visited the hospital for health
      screening were selected as the control group (Non-DM, n=160). Compared with
      control subjects, patients with T2DM had a lower serum 25(OH)D level (15.4+/-0.5
      vs. 12.9+/-0.4 ng/ml, p<0.01). Eleven percent of T2DM patients were VitD
      "insufficient" (20-29 ng/ml) and 87% of the patients were VitD "deficient" (<20
      ng/ml). The serum 25(OH)D level was significantly related to serum fibrinogen,
      triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ferritin, the
      urine albumin creatinine ratio, and hemoglobin A(1C) (HbA1C). In a multivariate
      logistic regression analysis, high levels of HbA1C, TG, and LDL-C were
      independently associated with VitD deficiency in T2DM patients. The results of
      the present study show that the majority of Koreans with T2DM are VitD deficient,
      and the serum 25(OH)D level in patients with T2DM is related to lipid and glucose
      parameters. Further studies are required of the relationship of VitD with
      fibrinogen and other related parameters.

PMID- 22977754
TI  - Clinical effect of a mixed solution of sodium hyaluronate and sodium
      carboxymethylcellulose during the transconjunctival approach for orbital wall
      reconstruction.
AB  - This study aimed to evaluate the anti-adhesive effect of a mixed solution of
      sodium hyaluronate and sodium carboxymethylcellulose (HACMC, Guardix-sol(r))
      during the transconjunctival approach to orbital wall reconstruction. Eighty
      seven patients who underwent orbital wall reconstruction by the transconjunctival
      approach were enrolled in this prospective study. We applied HACMC between the
      orbicularis oculi muscle and the orbital septum after surgery in 47 patients and
      did not use it in 40 patients. Lower lid retraction and marginal reflex distance
      2 (MRD(2)) were measured to analyze the degree of postoperative adhesion at 1
      week and 1, 3, and 6 months. The degree of MRD(2) showed clinically significant
      differences at postoperative 1 week and 1 month between the HACMC and control
      groups (p<0.05). Lower lid ectropion developed in two patients (5.0%) in the
      control group but did not occur in the HACMC group. In orbital wall
      reconstruction by the transconjunctival approach, the HACMC mixture solution is
      effective for preventing adhesion and lower lid ectropion during the early
      postoperative period.

PMID- 22977753
TI  - The effect of melatonin on retinal ganglion cell survival in ischemic retina.
AB  - Our objective was to determine whether melatonin increases retinal ganglion cell
      (RGC) survival in ischemic mouse retina. Transient retinal ischemia was induced
      by an acute elevation of intraocular pressure in C57BL/6 mice. To evaluate the
      effect of melatonin on retinal ischemia, an equal amount of either melatonin or
      vehicle was intraperitoneally injected into the mice 1 hour before ischemia, at
      the time of ischemia, and 1 hour after ischemia. Hypoxia inducible factor 1alpha
      (HIF-1alpha) and glial fibrillary acidic protein (GFAP) expression were assessed
      6, 12, and 24 hours after ischemia-reperfusion by Western blot. RGC survival was
      measured 2 weeks after ischemia-reperfusion. The expression of HIF-1alpha and
      GFAP peaked 24 hours after ischemia-reperfusion in ischemic retina. The treatment
      of ischemic retina with melatonin resulted in the inhibition of increased
      expression of HIF-1alpha and GFAP. RGC survival was greater in retinas treated
      with melatonin than in retinas treated with vehicle 2 weeks after ischemia
      reperfusion. On the basis of our results, we suggest that melatonin treatment
      increased RGC survival in ischemic mouse retina. The neuroprotective effect of
      melatonin is mediated by the inhibition of HIF-1alpha stabilization and reduced
      activity of glial cells in ischemic mouse retina.

PMID- 22977755
TI  - Hypercalcemia in a patient with polycythemia vera.
AB  - A 59-year-old female with diabetes mellitus presented with hypercalcemia and
      polycythemia. Her serum calcium and intact parathyroid hormone (iPTH) levels were
      increased, and Tc-99m sesta-MIBI scanning showed hot uptake in the lower portion
      of the left thyroid lobe. After parathyroidectomy, her calcium, iPTH, and
      polycythemia were normalized. In conclusion, the differential diagnosis of
      polycythemia and hypercalcemia should also include the possibility of a
      parathyroid tumor in addition to other neoplasms.

PMID- 22977756
TI  - Retrieval of a partially degloved stent strut during percutaneous coronary
      intervention.
AB  - Although stent entrapment is a rare event during percutaneous coronary
      intervention, stent entrapment can cause stent breakage or loss, which results in
      fatal complications such as stent embolism or acute myocardial infarction. We
      report one case of stent entrapment that was successfully treated by a snare via
      a contralateral transfemoral approach.

PMID- 22977757
TI  - Analysis of patients with anaplastic thyroid cancer expected to have curative
      surgery.
AB  - PURPOSE: Anaplastic thyroid cancer (ATC) is rare and has a poor prognosis. The
      aim of this study was to analyze the clinicopathologic characteristics of
      patients diagnosed with ATC expected to undergo curative thyroidectomy, with the
      goal of finding differences between patients surviving >=6 months and <6 months.
      METHODS: From 1981 to 2010, 24 patients underwent thyroidectomy due to ATC. Among
      those patients, 12 suspected of distant metastasis preoperatively were excluded.
      The remaining 12 patients were analyzed by retrospective review of electronic
      medical records. RESULTS: Median age was 55 years, and the male to female ratio
      was 1:5. All patients presented with neck mass at initial diagnosis. Five
      patients lived <6 months and seven patients lived >=6 months after operation. In
      patients surviving >=6 months, all lesions were <5 cm and all patients underwent
      total thyroidectomy. In patients surviving <6 months, two of the four lesions
      were >5 cm, and two of the five patients underwent less than total thyroidectomy
      (P = 0.287 and 0.152, respectively). All patients with lesion size <5 cm
      underwent total thyroidectomy and showed a shorter median operation time (P =
      0.182 and 0.033, respectively). CONCLUSION: ATC showed female predominance.
      Patients initially presented with neck mass, and median age was 55 years. In
      patients with ATC who are expected to undergo curative thyroidectomy, surgery
      should actively be considered as primary therapy for patient survival when the
      size is <5 cm.

PMID- 22977758
TI  - First experiences with laparoscopic assisted distal gastrectomy: in the view of
      comparison with high volume centers.
AB  - PURPOSE: Recently, the number of laparoscopic gastric surgeries increased in
      Korea. But since many patients prefer to attend larger hospitals, most operations
      have been performed in high volume center by experienced surgeons, and also most
      reported studies on laparoscopic gastric surgery have been performed in these
      hospitals. For better health service and increased access of local residents,
      district hospitals that have a smaller number of surgical cases also need to
      perform this surgery safely. METHODS: We retrospectively analyzed 58 patients who
      underwent laparoscopic assisted distal gastrectomy (LADG) from April 2009 to
      January 2012 in Dankook University Hospital. We compared our data with the
      retrospective data of the Korean Laparoendoscopic Gastrointestinal Surgery Study
      (KLASS) group because we thought the KLASS study was a representative study of
      LADG. RESULTS: A total of 58 patients underwent LADG during a period of 32
      months. The male to female ratio, mean age and body mass index were 34:19, 62.4
      years and 23.0 kg/m(2), respectively. More than D1 + beta lymph node was
      dissected in all patients and the mean number of harvested lymph nodes was 31.4.
      Mean operation time, estimated blood loss and mean hospital stays were 235
      minutes, 176 mL and 7.4 days respectively. During the operation, there were no
      complication and no conversions to open surgery. After the operation, there were
      2 cases of wound complication and 1 case of intra-abdominal abscess which
      improved with conservative treatment and there was no mortality. These data were
      not different to the data of high volume centers, especially KLASS. CONCLUSION:
      We report first experience with LADG and concluded that LADG could be performed
      safely in smaller scale hospitals.

PMID- 22977759
TI  - Outcome of total proctocolectomy with ileal pouch-anal anastomosis for ulcerative
      colitis.
AB  - PURPOSE: We evaluated the risk factors for late complications and functional
      outcome after total proctocolectomy (TPC) with ileal pouch-anal anastomosis
      (IPAA) for ulcerative colitis (UC). METHODS: Pre- and postoperative clinical
      status and follow-up data were obtained for 55 patients who underwent TPC with
      IPAA between 1999 and 2010. The median follow-up duration was 4.17 years. Late
      complications were defined as those that appeared at least one month after
      surgery. For a functional assessment, telephone interviews were conducted using
      the Global Assessment of Functioning Scale. Twenty-eight patients completed the
      interview. RESULTS: Late complications were found in 20 cases (36.3%), comprising
      pouchitis (n = 8), bowel obstruction (n = 5), ileitis (n = 3), pouch associated
      fistula (n = 2), and intra-abdominal infection (n = 2). The preoperative serum
      albumin level for patients with late complications was lower than for patients
      without (2.4 +/- 0.5 vs. 2.9 +/- 0.7, P = 0.04). Functional outcomes were not
      significantly associated with clinical characteristics, follow-up duration,
      operation indication, or late complications. CONCLUSION: This study demonstrated
      that a low preoperative albumin level could be a risk factor for late
      complications of TPC with IPAA. Preoperative nutritional support, especially
      albumin, could reduce late complications. Functional outcomes are not related to
      late complications.

PMID- 22977760
TI  - Risk factors for complications after bowel surgery in Korean patients with
      Crohn's disease.
AB  - PURPOSE: To assess the incidence and factors predictive of early postoperative
      complications in Korean patients who undergo surgery for Crohn's disease (CD).
      METHODS: We retrospectively assessed 350 patients (246 males, 104 females; mean
      age, 30 +/- 9 years) who underwent surgery for primary or recurrent CD at Asan
      Medical Center between January 1991 and May 2010. The incidence and predictive
      factors of early postoperative complications were analyzed by both univariate and
      multivariate analyses. RESULTS: Of the 350 patients, 81 patients (23.1%)
      developed postoperative complications, the most common being septic complications
      (54 patients), including 19 cases of wound infection. Thirty patients (8.6%)
      required re-operations, and only one patient died. Multivariate analysis showed
      that four factors were independently associated with a high risk of early
      postoperative complications; preoperative moderate to severe anemia (hematocrit
      concentration <30%; odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6 to
      5.9), hypoalbuminemia (serum albumin level <3.0 g/dL; OR, 2.6; 95% CI, 1.4 to
      4.7), emergency surgery (OR, 4.0; 95% CI, 1.5 to 10.6), and covering stoma (OR,
      2.6; 95% CI, 1.3 to 5.4). Correction of preoperative moderate to severe anemia
      and hypoalbuminemia decreased the incidence of postoperative complications. Mean
      hospital stay was significantly longer in patients with than without
      postoperative complications (31.3 +/- 27.2 days vs. 10.3 +/- 3.8 days, P <
      0.001). CONCLUSION: Preoperative anemia, low albumin level, emergency surgery,
      and covering stoma significantly increased the risk of early postoperative
      complications in patients with CD. Correcting preoperatively deficient
      nutritional factors may reduce postoperative morbidities.

PMID- 22977761
TI  - Laparoscopic left hemihepatectomy for left intrahepatic duct stones.
AB  - PURPOSE: The feasibility of laparoscopic left hemihepatectomy for the management
      of intrahepatic duct (IHD) stones was evaluated. METHODS: The clinical data of 26
      consecutive patients who underwent total laparoscopic left hemihepatectomy for
      IHD stones at Gyeongsang National University Hospital between January 2009 and
      June 2011 were reviewed retrospectively. RESULTS: The mean operation time was
      312.1 +/- 63.4 minutes and the mean postoperative hospital stay was 11.8 +/- 5.0
      days. There were 2 cases of postoperative bile leakage and 3 cases of intra
      abdominal fluid collection, which were successfully managed conservatively.
      Remnant stones were detected in 2 patients. The initial success rate of stone
      clearance was 92.3% (24 of 26). The remnant stones were located in the common
      bile duct in both cases and were removed by endoscopic retrograde
      cholangiopancreatography and endoscopic sphincterotomy. Therefore, the final
      success rate of stone clearance was 100% (26 of 26). During a mean follow-up of
      22 months (range, 7 to 36 months), there was no patient with recurrent stone.
      CONCLUSION: Laparoscopic surgery could be an effective treatment modality for the
      management of IHD stones in select patients.

PMID- 22977762
TI  - Is close monitoring in the intensive care unit necessary after elective liver
      resection?
AB  - PURPOSE: Many surgical patients are admitted to the intensive care unit (ICU),
      resulting in an increased demand, and possible waste, of resources. Patients who
      undergo liver resection are also transferred postoperatively to the ICU. However,
      this may not be necessary in all cases. This study was designed to assess the
      necessity of ICU admission. METHODS: The medical records of 313 patients who
      underwent liver resections, as performed by a single surgeon from March 2000 to
      December 2010 were retrospectively reviewed. RESULTS: Among 313 patients, 168
      patients (53.7%) were treated in the ICU. 148 patients (88.1%) received only
      observation during the ICU care. The ICU re-admission and intensive medical
      treatment significantly correlated with major liver resection (odds ratio [OR],
      6.481; P = 0.011), and intraoperative transfusions (OR, 7.108; P = 0.016).
      Patients who underwent major liver resection and intraoperative transfusion were
      significantly associated with need for mechanical ventilator care, longer
      postoperative stays in the ICU and the hospital, and hospital mortality.
      CONCLUSION: Most patients admitted to the ICU after major liver resection just
      received close monitoring. Even though patients underwent major liver resection,
      patients without receipt of intraoperative transfusion could be sent to the
      general ward. Duration of ICU/hospital stay, ventilator care and mortality
      significantly correlated with major liver resection and intraoperative
      transfusion. Major liver resection and receipt of intraoperative transfusions
      should be considered indicators for ICU admission.

PMID- 22977764
TI  - Enteral nutrition associated non-occlusive bowel ischemia.
AB  - We describe two patients, with no previous history of vascular problems but poor
      lung function, who experienced septic shock due to bowel ischemia. Both were fed
      an enteral formula rich in fiber using a feeding tube and experienced septic
      shock with regular enteral feeding. Surgical finding showed hemorrhagic ischemia
      in the bowel. The pathologic finding suggests these changes may have been due to
      inspissations of bowel contents, which may put direct pressure on the mucosa of
      the bowel wall, leading to local impairment of mucosal and submucosal blood flow
      with subsequent bowel necrosis. Bowel ischemia may have been precipitated by an
      increased mesenteric blood flow requirement in combination with a metabolically
      stressed bowel. Patients in the intensive care unit fed a fiber-rich enteral
      formula may have inspissated bowel contents, leading to bowel ischemia,
      suggesting that the use of fiber-rich formula should be limited in patients at
      high-risk of bowel ischemia.

PMID- 22977763
TI  - Renal and abdominal visceral complications after open aortic surgery requiring
      supra-renal aortic cross clamping.
AB  - PURPOSE: The aim of this study was to assess renal or abdominal visceral
      complications after open aortic surgery (OAS) requiring supra-renal aortic cross
      clamping (SRACC). METHODS: We retrospectively reviewed the medical records of 66
      patients who underwent SRACC. Among them, 17 followed supra-celiac aortic cross
      clamping (SCACC) procedure, 42 supra-renal, and 7 inter-renal aorta.
      Postoperative renal, hepatic or pancreatic complications were investigated by
      reviewing levels of serum creatinine and hepatic and pancreatic enzymes.
      Preoperative clinical and operative variables were analyzed to determine risk
      factors for postoperative renal insufficiency (PORI). RESULTS: Indications for
      SRACC were 25 juxta-renal aortic occlusion and 41 aortic aneurysms (24 juxta
      renal, 12 supra-renal and 5 type IV thoraco-abdominal). The mean duration of
      renal ischemic time (RIT) was 30.1 +/- 22.2 minutes (range, 3 to 120 minutes).
      PORI developed in 21% of patients, including four patients requiring hemodialysis
      (HD). However, chronic HD was required for only one patient (1.5%) who had
      preoperative renal insufficiency. RIT >= 25 minutes and SCACC were significant
      risk factors for PORI development by univariate analysis, but not by multivariate
      analysis. Serum pancreatic and hepatic enzyme was elevated in 41% and 53% of the
      17 patients who underwent SCACC, respectively. CONCLUSION: Though postoperative
      renal or abdominal visceral complications developed often after SRACC, we found
      that most of those complications resolved spontaneously unless there was
      preexisting renal disease or the aortic clamping time was exceptionally long.

PMID- 22977765
TI  - Left-sided appendicitis in a patient with situs inversus totalis.
AB  - Situs inversus totalis is a rare inherent disease in which the thoracic and
      abdominal organs are transposed. Symptoms of appendicitis in situs inversus (SI)
      may appear in the left lower quadrant, and the diagnosis of appendicitis is very
      difficult. We report a case of left-sided appendicitis diagnosed preoperatively
      after dextrocardia that was detected by chest X-ray, although the chief complaint
      of the patient was left lower-quadrant pain. The patient underwent an emergent
      laparoscopic appendectomy under the diagnosis of appendicitis after abdominal
      computed tomography (CT). In patients with left lower quadrant pain, if the chest
      X-ray shows dextrocardia, one should suspect left-sided appendicitis. A strong
      suspicion of appendicitis and an emergency laparoscopic operation after
      confirmation of the diagnosis by imaging modalities including abdominal CT or
      sonography can reduce the likelihood of misdiagnosis and complications including
      perforation and abscess. Laparoscopic appendectomy in SI was technically more
      challenging because of the mirror nature of the anatomy.

PMID- 22977766
TI  - Incarcerated internal hernia within a huge irreducible parastomal hernia with
      intestinal obstruction: a rare case report of "hernia within hernia".
AB  - We report an incarcerated internal hernia in a huge irreducible parastomal hernia
      "hernia within hernia." A 70-year-old obese woman with diabetes who underwent an
      abdomino-perineal resection 20 years ago was admitted to our hospital with 20
      years history of a huge irreducible bulge, 25 cm in diameter. An internal hernia
      due to an adhesive band extending from the sac wall to proximal colon was found
      in the parastomal hernia sac during an emergency laparotomy. We cut off the
      distal colon and relocated the colostomy stoma. The patient was discharged
      uneventfully 2 weeks after the surgery and was readmitted to have a further
      laparoscopic hernia repair 8 months later. Unfortunately, an unrecognized
      enterotomy occurred during the secondary surgery that led to an additional
      laparotomy during which the mesh was not contaminated by the bowel contents and
      was kept in place. At 22-month follow-up, there were no evidences of recurrence.

PMID- 22977767
TI  - Stent fractures after superficial femoral artery stenting.
AB  - Stent fracture is one of the major factors compromising implanted stent patency
      due to its consequences including in-stent restenosis, thrombosis, perforation,
      and migration. Stent fracture can occur from stress (extrinsic or intrinsic) and
      biomechanical forces at different implantation sites. We report on 2 cases of
      stent fractures and pertinent literature. One patient, a 75-year-old male,
      presented with recurrence of claudication 14 months after superficial femoral
      artery stenting; a femoral artery occlusion with stent fracture was found, and he
      underwent femoropopliteal bypass. The other patient, a 72-year-old male presented
      with recurrence of claudication; a stent fracture was found without femoral
      artery occlusion, and he was treated with additional femoral artery stenting to
      secure the fracture site.

PMID- 22977768
TI  - The Impacts of ACE Activity according to ACE I/D Polymorphisms on Muscular
      Functions of People Aged 65.
AB  - OBJECTIVE: To investigate associations between angiotensin-converting enzyme
      (ACE) polymorphisms and muscle fatigability in 65-year-old Koreans. METHOD: The
      study participants were 49 Koreans aged 65 years. ACE insertion/deletion (I/D)
      polymorphisms were determined by polymerase chain reaction and serum ACE
      activity, by spectrophotometry. Body mass index (BMI), body fat mass (BFM), and
      lean body mass (LBM) were determined. To evaluate muscle fatigability, dynamic
      Electromyography was used to measure maximum voluntary isometric contractions
      (MVICs) of ankle plantar flexor muscles. Patients were seated with their hips
      flexed at 90 degrees , knees fully extended, and ankles at 0 degrees . Continuous
      submaximal VICs (40% MVIC) were then performed, and contraction duration and EMG
      frequency changes during the initial 2 min were measured. A self-reported
      physical activity questionnaire was used to evaluate effects of ACE activity
      levels on muscle fatigability. RESULTS: Among the 49 volunteers, 15 showed II
      genotype; 22, ID genotype; and 12, DD genotype. Serum ACE activity levels were
      significantly higher in DD genotype subjects than in II genotype subjects
      (p<0.05). Furthermore, the duration of submaximal isometric contractions was
      longer in II and ID genotype subjects than in DD genotype subjects (p<0.05).
      Dynamic EMG showed significantly lower mean frequency changes in II genotype
      subjects than in DD genotype subjects (p<0.05). However, LBM, BFM, and BMI were
      independent of ACE genotypes. CONCLUSION: ACE II genotype subjects showed
      significantly higher resistant to muscle fatigue than that by DD genotype
      subjects. However, body composition and BMI showed no correlations with ACE I/D
      polymorphisms.

PMID- 22977769
TI  - The effect of recombinant human growth hormone therapy in patients with completed
      stroke: a pilot trial.
AB  - OBJECTIVE: To evaluate the safety and potential efficacy of "recombinant human
      growth hormone (rhGH)" on the functional recovery of completed stroke patients.
      METHOD: Completed stroke patients were recruited. All participants were randomly
      assigned to the GH group (rhGH injection and rehabilitative therapy) or the
      control group (only rehabilitative therapy). Above all, they were closely
      monitored for safety. Further, for the efficacy measurement, Korean Modified
      Barthel Index (K-MBI), Manual Muscle strength Test (MMT), and Fugl-Meyer
      assessment (FMA) were assessed to determine the changes of functional recovery
      during 6-months of the study period. Along with it, diffusion tensor image was
      taken as the baseline, and a followed-up study to observe the changes in
      diffusion tensor tractography (DTT), during the period, and one patient in the GH
      group was also examined with functional MRI (fMRI). Index of fatigue on 5 point
      scale for the study period was also assessed. RESULTS: Twenty-two patients were
      enrolled, and 15 completed the study and were included in the analysis. No
      harmful adverse events were observed in the GH group. By comparison between the
      groups, the GH group showed more improvement in K-MBI than the control group
      (p<0.05). DTT showed less decrement of fibers in the GH group than in the control
      group, without statistical significance. fMRI showed an increment in the
      activated area. Patients in the GH group expressed no fatigue at all, during the
      study period (p=0.00). CONCLUSION: The administration of rhGH in long term
      resulted in the improvement in K-MBI, and subjectively less tiredness during the
      injection period.

PMID- 22977770
TI  - The effects of intra-articular platelet-rich plasma injection according to the
      severity of collagenase-induced knee osteoarthritis in a rabbit model.
AB  - OBJECTIVE: To investigate whether the cartilage regenerative effects of intra
      aricular platelet-rich plasma (PRP) are different, according to the severity of
      osteoarthritis (OA), in a collagenase-induced knee OA rabbit model. METHOD: New
      Zealand white rabbits (N=21) were randomly divided into three groups. Three
      different doses (0.25 mg, group 1; 0.5 mg, group 2; and 1.0 mg, group 3) of
      collagenase were injected twice into both knees of each group under an ultrasound
      guidance. The mean platelet concentration of the PRP fraction was 2,664+/
      970*10(3)/ul and was enriched 8.2-times, compared with the whole blood. PRP (0.3
      ml) was injected into the left knee and saline (0.3 ml) into the right knee at 4
      weeks, and macroscopic and histological scores of both injected knees were
      evaluated at 9 weeks after the first collagenase injection. RESULTS: Macroscopic
      and histological scores of group 3 were significantly higher than those of group
      1 and 2 (p<0.05). Macroscopic and histological scores of the PRP-injected knees
      were significantly lower than those of the saline-injected knees, in all groups
      (p<0.05). Differences of gross morphologic and histologic scores between saline-
      and PRP-injected knees in group 3 were significantly higher than those in group 1
      and 2 (p<0.05). CONCLUSION: Intra-articular PRP injection influences cartilage
      regeneration in all severities of rabbit knee OA, and the cartilage regenerative
      power of PRP injection in moderate knee OA was greater than that in mild or very
      mild OA. A large preclinical trial is needed to establish the validity of our
      study.

PMID- 22977771
TI  - The effect of hyaluronidase in interlaminar lumbar epidural injection for failed
      back surgery syndrome.
AB  - OBJECTIVE: To evaluate the effect of hyaluronidase in patients with failed back
      surgery syndrome (FBSS) treated with interlaminar lumbar epidural injection
      (ILEI). METHOD: Sixty patients suffering from severe low back pain and sciatica
      were randomly allocated into three groups. Group T received ILEI with 2 ml
      triamcinolone 40 mg/ml and 5 ml bupivacaine 0.25%. Group H received ILEI with
      1500 IU hyaluronidase and 5 ml bupivacaine 0.25%. Group TH received interlaminar
      lumbar epidural injection (ILEI) with 1500 IU hyaluronidase, 2 ml triamcinolone
      40 mg/ml and 5 ml bupivacaine 0.25%. The effect was evaluated using Visual
      Analogue Scale (VAS) and Oswestry Disability Index (ODI) at pre-injection, 2
      weeks, 6 weeks and 12 weeks after ILEI. RESULTS: After 2 weeks and after 6 weeks,
      patients in both Group T and Group TH had significant effectiveness more than
      Group H in decrease of VAS and ODI. After 12 weeks, only patients in Group TH had
      significant effectiveness in decrease of VAS and ODI (p<0.05). In every period,
      Group TH had the most effectivess in decrease of VAS and ODI after ILEI.
      CONCLUSION: ILEI for FBSS with triamcinolone and hyaluronidase is considered to
      have more long term effectiveness to reduce pain and improve function after ILEI
      than injection with triamcinolone alone or hyaluronidase alone.

PMID- 22977772
TI  - Contrast spreading patterns in retrodiscal transforaminal epidural steroid
      injection.
AB  - OBJECTIVE: To observe the contrast spreading patterns in the retrodiscal (RD)
      approach for transforaminal epidural steroid injections and their effect on pain
      reduction. METHOD: Patients with L5 radiculopathy who were scheduled to receive
      lumbar TF-EPB were consecutively included. We randomly divided them into the L4-5
      RD and L5-S1 RD groups and administered 1 cc of contrast dye into epidural space.
      We observed the shape and the location of contrast dye on the anterior-posterior
      and lateral views. We injected 1 cc of 0.5% lidocaine mixed with 20 mg of
      triamcinolone, and checked the pain intensity before and two weeks after the
      procedure by using visual analogue scale (VAS). RESULTS: In the L4-5 RD group
      (n=30), contrast spread over the L4 nerve root in 27 cases and the L4 and L5
      nerve roots in 3 cases. In the L5-S1 RD group (n=33), contrast spread over the L5
      nerve root in 20 cases, the S1 nerve root in 3 cases, and the L5 and the S1 nerve
      roots in 10 cases. The contrast spreading patterns could be divided into 4
      patterns: the proximal root in 40 cases, the distal root in 19 cases, the
      anterior epidural space in 3 cases and an undefined pattern in 1 case.
      CONCLUSION: In RD lumbar TF-EPB, the contrast dye mostly went into the cephalic
      root and about 60% spread over the proximal nerve root. There was less pain
      reduction when the contrast dye spread over the distal nerve root.

PMID- 22977773
TI  - Injectate Volumes Needed to Reach Specific Landmarks and Contrast Pattern in
      Kambin's Triangle Approach with Spinal Stenosis.
AB  - OBJECTIVE: To identify the volumes of contrast material needed to reach the
      specific landmarks and contrast pattern during Kambin's triangle approach (KB-A)
      in lumbar spinal stenosis. METHOD: Sixty patients undergoing KB-A were
      investigated. Fifty-six patients were included in this study. KB-A were performed
      with the use of contrast-enhanced fluoroscopic visualization. After confirming
      the appropriate spinal needle position, a slow injection of up to 5.0 ml of
      nonionic contrast material was carried out. Under intermittent fluoroscopic
      guidance, contrast volumes were recorded as flow reached specific anatomic
      landmarks: ipsilateral inferior or superior neural foramen. RESULTS: After 2.0 ml
      of contrast was injected, 93.2% of KB-A cases spread to the medial aspect of the
      inferior pedicle of the corresponding level of injection and 86.3% of KB-A spread
      to the medial aspect of the superior pedicle of the corresponding level of
      injection. After 3 ml of contrast was injected, 95.3% of KB-A spread to cover
      both the medial aspect of the inferior pedicle and the superior pedicle of the
      corresponding level of injection. A volume of 2 ml of injectate reaches the
      anterior epidural space 100% of the time. CONCLUSION: This study demonstrates
      injectate volumes needed to reach the specific anatomic landmarks in KB-A. A
      volume of 3.0 ml of injectate reaches both the medial aspect of theinferior
      pedicle and the superior pedicle 94.6% of the time. Therefore, Interventionalists
      may consider a 1-level instead of a 2-level injection for patients with a
      bleeding risk or for 2 level central pathology.

PMID- 22977774
TI  - Reliability of the supraspinatus muscle thickness measurement by ultrasonography.
AB  - OBJECTIVE: To assess the intrarater and interrater reliability of the
      supraspinatus thickness measured by ultrasonography (US) in normal subjects and
      to identify the relationship between the supraspinatus thickness measured by US
      and cross sectional area (CSA) of the supraspinatus muscle by magnetic resonance
      imaging (MRI) in hemiplegic patients. METHOD: We examined 20 shoulders of normal
      subjects and 10 shoulders of hemiplegic patients. In normal subjects, one
      examiner measured the supraspinatus thickness twice by US at the scapular notch
      and another examiner measured the supraspinatus thickness several days later. The
      intrarater and interrater reliability of supraspinatus thickness measurements
      were then evaluated. In hemiplegic patients, the supraspinatus thickness at the
      scapular notch was measured by US in affected side and compared with CSA of the
      supraspinatus muscle at the scapular notch and the Y-view of MRI. RESULTS: One
      examiner's supraspinatus thickness measurement average was 1.72+/-0.21 cm and
      1.74+/-0.24 cm, and the other examiner's supraspinatus thickness measurement
      average was 1.74+/-0.22 cm in normal subjects. Intraclass correlation
      coefficients of intrarater and interrater examination were 0.91 and 0.88,
      respectively. For hemiplegic patients, the supraspinatus thickness measured by US
      was 1.66+/-0.13 cm and CSA by MRI was 4.83+/-0.88 cm(2) at the Y-view and 5.61+/
      1.19 cm(2) at the scapular notch. The Pearson Correlation Coefficient between the
      supraspinatus thickness at the scapular notch and the CSA at the Y-view was 0.72
      and that between the supraspinatus thickness and CSA at the scapular notch was
      0.76. CONCLUSION: The supraspinatus thickness measurement by US is a reliable
      method and is positively correlated with the CSA of the supraspinatus muscle in
      MRI in hemiplegic patients. Therefore, supraspinatus thickness measurement by US
      can be used in the evaluation of muscle atrophy and to determine therapeutic
      effects in hemiplegic patients.

PMID- 22977775
TI  - Real-time visualization of ultrasonography guided cubital tunnel injection: a
      cadaveric study.
AB  - OBJECTIVE: To describe an ultrasonography-guided technique for cubital tunnel
      injection. METHOD: The ulnar nerves from 12 elbows of 6 adult cadavers were
      scanned, and the cross-sectional areas of the ulnar nerves, cubital tunnel inlets
      and outlets were measured by using ultrasonography. All elbows were dissected
      after an ultrasonography-guided dye injection at the inlet of the cubital tunnel.
      The dissectors evaluated the spread of dye and the coloration of the nerve and
      remeasured the cross-sectional areas of the cubital tunnel inlets and outlets.
      RESULTS: After a real-time visualization of an ultrasonography-guided injection,
      the ulnar nerves were seperated from the medial groove for the ulnar nerve. All
      the ulnar nerves of the cadavers were successfully colored with the dye, from the
      inlet to oulet of the cubital tunnel. The post-injection cross-sectional areas
      were significantly larger than the pre-injection cross-sectional areas. No
      significant differences were detected in the post-injection cross-sectional areas
      of the cubital tunnel outlet and the ulnar nerve as compared with the pre
      injection areas. CONCLUSION: Clinicians should consider real-time visualization
      of ultrasonography for guided injection around the ulnar nerve at the inlet of
      the cubital tunnel.

PMID- 22977776
TI  - Prediction of Motor Function Recovery after Subcortical Stroke: Case Series of
      Activation PET and TMS Studies.
AB  - OBJECTIVE: To examine whether the pattern of brain activation induced by a motor
      task and the motor responses to transcranial magnetic stimulation (TMS) have
      prognostic implications for motor recovery after stroke. METHOD: Ten patients
      with first-ever subcortical stroke (55.7+/-17.3 years, 5 ischemic and 5
      hemorrhagic) underwent 2 FDG PET studies under different conditions (1: rest, 2:
      activation with a specific motor task) at 37.7+/-25.2 days after stroke. The
      regions showing more than a 10% increase in glucose metabolism on subtraction
      images during activation and rest were considered to be significantly activated.
      Cortical excitability of intracortical inhibition (ICI) and intracortical
      facilitation (ICF) were assessed using the TMS from both abductor pollicis brevis
      muscles within 7 days of PET scans. Recovery of motor function was assessed at
      the point of the neurological plateau. RESULTS: The presence of a motor response
      at the plegic site to TMS and normal intracortical inhibition, and facilitation
      patterns in the unaffected hemisphere were found to be related to good recovery.
      An association between an ipsilesional activation on PET and good motor recovery
      was also observed, but this was significantly weaker than that between TMS
      measured cortical excitability and motor recovery. CONCLUSION: Integrity of the
      ipsilesional corticospinal pathway, normalized contralesional intracortical
      excitability, and task-related activation in the ipsilesional hemisphere were
      found to predict post-stroke motor recovery significantly.

PMID- 22977777
TI  - The effect of bedside exercise program on stroke patients with Dysphagia.
AB  - OBJECTIVE: To examine the effects of a bedside exercise program on the recovery
      of swallowing after a stroke. METHOD: Fifty stroke patients with dysphagia (<6
      months post-stroke) were enrolled and classified into two groups, the
      experimental (25 subjects) and control groups (25 subjects). The control group
      was treated with conventional swallowing therapy. The experimental group received
      additional bedside exercise training, which consisted of oral, pharyngeal,
      laryngeal, and respiratory exercises, 1 hour per day for 2 months, and they were
      instructed regarding this program through the nursing intervention. All patients
      were assessed for their swallowing function by Videofluoroscopic Swallowing Study
      (VFSS), using the New VFSS scale, the level of functional oral intake, the
      frequency of dysphagia complications, the presence (or not) of tube feeding, the
      mood state and quality of life before the treatment and at 2 months after the
      treatment. RESULTS: After 2 months of treatment, the experimental group showed a
      significant improvement in the swallowing function at the oral phase in the New
      VFSS Scale than that of the control group (p<0.05). Further, they also showed
      less depressive mood and better quality of life than the control group. However,
      there was no significant change in the incidence of dysphagia complication and
      the presence (or not) of tube feeding between the two groups. CONCLUSION: Bedside
      exercise program showed an improvement of swallowing function and exhibited a
      positive secondary effect, such as mood state and quality of life, on subacute
      stroke patients with dysphagia. For improvement of rehabilitation results on
      subacute stroke patients with dysphagia, this study suggests that additional
      intensive bedside exercise would be necessary.

PMID- 22977778
TI  - Feasibility and effects of newly developed balance control trainer for mobility
      and balance in chronic stroke patients: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the feasibility and effects of balance training with a
      newly developed Balance Control Trainer (BCT) that applied the concept of
      vertical movement for the improvements of mobility and balance in chronic stroke
      patients. METHOD: Forty chronic stroke patients were randomly assigned to an
      experimental or a control group. The experimental group (n=20) underwent training
      with a BCT for 20 minutes a day, 5 days a week for 4 weeks, in addition to
      concurrent conventional physical therapy. The control group (n=20) underwent only
      conventional therapy for 4 weeks. All participants were assessed by: the
      Functional Ambulation Categories (FAC), 10-meter Walking Test (10mWT), Timed Up
      and Go test (TUG), Berg Balance Scale (BBS), Korean Modified Barthel Index (MBI),
      and Manual Muscle Test (MMT) before training, and at 2 and 4 weeks of training.
      RESULTS: There were statistically significant improvements in all parameters
      except knee extensor power at 2 weeks of treatment, and in all parameters except
      MBI which showed further statistically significant progress in the experimental
      group over the next two weeks (p<0.05). Statistically significant improvements on
      all measurements were observed in the experimental group after 4 weeks total.
      Comparing the two groups at 2 and 4 weeks of training respectively, 10mWT, TUG,
      and BBS showed statistically more significant improvements in the experimental
      group (p<0.05). CONCLUSION: Balance training with a newly developed BCT is
      feasible and may be an effective tool to improve balance and gait in ambulatory
      chronic stroke patients. Furthermore, it may provide additional benefits when
      used in conjunction with conventional therapies.

PMID- 22977779
TI  - Factors that Influence Quiet Standing Balance of Patients with Incomplete
      Cervical Spinal Cord Injuries.
AB  - OBJECTIVE: To investigate the factors influencing the quiet standing balance of
      patients with incomplete cervical spinal cord injuries. Also to find the
      correlations between posturographic parameters and clinical balance tests as well
      as to find the correlation between posturographic parameters and functional
      independence. METHOD: We conducted a tetra-ataxiometric posturography, lower
      extremity motor score (LEMS), Korean version of the Berg Balance Scale (K-BBS),
      Timed Up and Go test (TUG), and Korean Version of the Modified Barthel Index (K
      MBI) of 10 patients. 10 healthy adults carried out the posturography. We checked
      stability, weight distribution, Fourier and synchronization indices of eight
      positions, and the fall index of the posturography. RESULTS: The patient group
      showed significantly higher stability and weight distribution indices in all
      eight positions. Stability indices significantly increased with eyes closed or
      standing on pillows. Weight distribution indices were significantly higher with
      eyes closed or the head bent backwards. The patient group showed significantly
      higher Fourier indices of low, low-medium, and high frequency in eight positions.
      The Fourier indices at high-medium frequency were significantly higher with eyes
      closed on pillows or in variable head positions. There were no significant
      differences of synchronization indices between the patient and the control group.
      The falling index of the patient group significantly correlated with K-BBS, TUG,
      and K-MBI. LEMS had significant correlation with some synchronization indices,
      but not with the falling index. CONCLUSION: The quiet standing balance of the
      patients was influenced by somatosensory limitations or insufficient visual
      compensation. We should try to improve the postural balance and functional
      independence of patients through proper proprioceptive and lower extremity
      strength training for better postural and pedal control, and to make efforts to
      minimize environmental hazards.

PMID- 22977780
TI  - The Correlation between Modified Ashworth Scale and Biceps T-reflex and Inter
      rater and Intra-rater Reliability of Biceps T-reflex.
AB  - OBJECTIVE: To establish a correlation between the modified Ashworth scale (MAS)
      and amplitude and latency of T-reflex and to demonstrate inter-rater and intra
      rater reliability of the T-reflex of the biceps muscle for assessing spasticity
      after stroke. METHOD: A total of 21 patients with hemiplegia and spasticity after
      ischemic stroke were enrolled for this study. The spasticity of biceps muscle was
      evaluated by an occupational therapist using the MAS. The mean value of manual
      muscle test of biceps muscles was 2.3+/-0.79. Latency and amplitude of T-reflex
      were recorded from biceps muscles by two physicians. The onset latency and peak
      to peak amplitude of the mean of 5 big T-reflex were measured. The examinations
      were carried out by two physicians at the same time to evaluate the inter-rater
      reliability. Further, one of the physicians performed the examination again after
      one week to evaluate the intra-rater reliability. The correlations between MAS
      and T-reflex, and the intra- and inter-rater reliability of biceps T-reflex were
      established by calculating the Spearman correlation coefficients and the intra
      class correlation coefficients (ICCs). RESULTS: Amplitude of the biceps T-reflex
      increased with increasing level of MAS (r(s)=0.464 and 0.573, respectively,
      p<0.01). ICCs of latency and amplitude of biceps T-reflex were 0.914 and 0.822.
      The Spearman correlation coefficients of latency and amplitude of biceps T-reflex
      were 0.937 and 0.635, respectively (p<0.01). CONCLUSION: Biceps T-reflex
      demonstrates a good quantitative measurement and correlation tool with MAS for
      spasticity, and also shows acceptable inter- and intra-rater reliability, which
      can be used for patients with spasticity after stroke.

PMID- 22977781
TI  - The Predictive Value of SigmaDeltaST/DeltaHR Index for Restenosis after
      Percutaneous Coronary Intervention.
AB  - OBJECTIVE: To find out the predictive value of the SigmaDeltaST/DeltaHR index for
      restenosis after percutaneous coronary intervention (PCI). METHOD: Subjects of
      this research were patients who participated in a cardiac rehabilitation (CR)
      program as six to eight weeks of a hospital-based program after receiving PCI to
      treat acute coronary syndrome (ACS). The patients received coronary angiography
      (CAG) at the onset of the ACS and nine months after that, and also received an
      exercise tolerance test (ETT) at the start of the CR program and several days
      before receiving a follow-up CAG. In ETT, we used the sum of the ST depression
      (SigmaDeltaST index) of leads II, III, aVF, V(4-6) as well as the sum of the
      DeltaST/DeltaHR (heart rate) (SigmaDeltaST/DeltaHR index) in the same leads and
      the sum of the DeltaST/DeltaRPP (rate pressure product) (SigmaDeltaST/DeltaRPP
      index) in the same leads. We compared the predictive power of each index of ETT
      for restenosis after PCI. RESULTS: The sensitivity, specificity, positive
      predictive value, and negative predictive value of SigmaDeltaST index were 69%,
      47%, 31%, and 82%. The SigmaDeltaST/DeltaHR index was 13.7+/-5.2 in the
      restenosis group and 9.3+/-5.6 in the patent group (p=0.017). The sensitivity,
      specificity, positive predictive value, and negative predictive value of this
      index were 85%, 63%, 44%, and 92%. The SigmaDeltaST/DeltaRPP index were 0.10+/
      0.08 in the restenosis group and 0.06+/-0.04 in the patent group (p=0.016). The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of this index were 54%, 76%, 44%, and 83%. CONCLUSION: The
      SigmaDeltaST/DeltaHR index showed a much higher sensitivity and negative
      predictive value for restenosis after PCI compared to the SigmaDeltaST index.

PMID- 22977782
TI  - Fornix injury in a patient with rotavirus encephalopathy: diffusion tensor
      tractography study.
AB  - Rotavirus encephalopathy (RE) is a benign afebrile seizure associated with acute
      gastroenteritis caused by rotavirus infection. We investigated the diffusion
      tensor tractography (DTT) findings of a patient with RE. The patient was a 30
      month-old female that had experienced a brief, generalized convulsive seizure. On
      the day of admission, the patient had vomiting and experienced watery diarrhea.
      Her stool was positive for rotavirus antigen. At onset, the patient displayed a
      drowsy and delirious mental status; later, a splenial lesion of the corpus
      callosum was found on MRI. One week later, the patient's condition improved and
      the splenial lesion had disappeared by conventional MRI. Initial DTI showed
      decreased fractional anisotropy (FA) values of fornix, as well as of the corpus
      callosum. A follow-up DTT showed a restored interrupted right fonical crus and
      increased FA values of corpus callosum and fornix. These results highlight the
      implications of the probability of not only a corpus callosum injury, but a
      fornix injury as well, in this patient with RE.

PMID- 22977783
TI  - Alien hand syndrome in stroke - case report & neurophysiologic study -.
AB  - Alien Hand Syndrome is defined as unwilled, uncontrollable, but seemingly
      purposeful movements of an upper limb. Two major criteria for the diagnosis are
      complaint of a foreign limb and complex, autonomous, involuntary motor activity
      that is not part of an identifiable movement disorder. After a cerebrovascular
      accident in the corpus callosum, the parietal, or frontal regions, various
      abnormal involuntary motor behaviors may follow. Although different subtypes of
      Alien Hand Syndrome have been distinguished, this classification clearly does not
      cover the wide clinical variety of abnormal motor behaviors of the upper
      extremity. And there are few known studies about the neurophysiology of this
      syndrome using transcranial magnetic stimulation (TMS). We recently experienced 2
      rare cases of Alien Hand Syndrome which occurred after anterior cerebral artery
      (ACA) infarction. A 72 year-old male with right hemiplegia following a left ACA
      infarct had difficulty with voluntarily releasing an object from his grasp. A 47
      year-old female with left hemiplegia following a right ACA infarct had a problem
      termed 'intermanual conflict' in which the two hands appear to be directed at
      opposing purposes. Both of them had neurophysiologic studies done, and showed
      reduced amplitude by single pulse MEP and a lack of intracortical inhibition
      (ICI) by paired pulse TMS. No abnormalities were found in SSEP.

PMID- 22977784
TI  - Lance-adams syndrome.
AB  - It is not common for a patient who survives cardiac arrest to experience
      significant neurologic impairment such as acute and chronic post-hypoxic
      myoclonus, known as Lance-Adams syndrome. This syndrome is predominantly
      characterized by myoclonus that starts days to weeks after cardiopulmonary
      resuscitation in patients who regained consciousness. Although several cases of
      LAS were reported, the decisive treatment method has not been established. We
      report a 43 year old man with Lance-Adams syndrome who showed long-term
      improvement through treatment with anti-myoclonic agents and participation in a
      rehabilitation program.

PMID- 22977785
TI  - Retropharyngeal abscess initially diagnosed by the videofluoroscopic swallowing
      study.
AB  - In this article, we report a case where a videofluoroscopic swallowing study
      (VFSS) revealed the cause of a recently developed idiopathic dysphagia in a 66
      year-old patient and enabled emergent treatment. The patient reported a 10-day
      history of fever, cough, sputum production, and progressive jaundice. He was then
      admitted to the hospital with suspicion of aspiration pneumonia. Despite
      treatment with antibiotics, fever and leukocytosis were persistent. As he also
      reported dysphagia, we performed the VFSS, which showed subglottic aspiration on
      all types of food and revealed a retropharyngeal mass causing mechanical
      compression. A contrast-enhanced computerized tomography (CT) of his neck was
      performed following the VFSS, which helped diagnose the mass as an extensive
      retropharyngeal abscess with mediastinitis. Following this diagnosis, emergent
      surgical incision and drainage was performed on the patient. Although the VFSS is
      primarily designed to evaluate swallowing function rather than to diagnose a
      disease, it can be used to reveal the primary medical cause of dysphagia while it
      studies the mechanical and structural abnormalities in the oropharyngeal and
      esophageal regions. This study also proposes that retropharyngeal abscess should
      be considered in the differential diagnosis of cases showing progressive
      dysphagia with fever. As confirmed through this work, the VFSS can function as a
      useful tool for detecting crucial diseases accompanying deglutition disorder.

PMID- 22977786
TI  - Upper thoracic myelopathy caused by delayed neck extensor weakness in myotonic
      dystrophy.
AB  - Myotonic dystrophy is the most common autosomal dominant myopathy in adults. Our
      patient, a 41 year-old female suffering from myotonic muscular dystrophy,
      developed upper thoracic myelopathy due to hypertrophy of the ligamentum flavum
      and the posterior longitudinal ligament. She had a typical hatchet face and
      ptosis with "head hanging forward" appearance caused by neck weakness. Motor
      weakness, sensory changes and severe pain below T4 level, along with urinary
      incontinence began 3 months ago. Genetic and electrodiagnostic studies revealed
      myotonic dystrophy type 1. Magnetic resonance imaging of the spine showed loss of
      cervical lordosis and spinal cord compression due to hypertrophied ligamentum
      flavum and posterior longitudinal ligament at T1 to T3 level. We concluded that
      her upper thoracic myelopathy was likely related to the thickness of the
      ligamentum flavum and posterior longitudinal ligament due to repetitive
      mechanical stress on her neck caused by neck muscle weakness with myotonic
      dystrophy.

PMID- 22977787
TI  - Shoulder Joint Infectious Arthritis and Acromioclavicular Joint Osteomyelitis due
      to Candida.
AB  - Candida species inhabit the skin and mucous membranes of healthy individuals with
      low virulence, and osteomyelitis due to candida is very rare. However, the
      incidence of invasive candidal infection caused by intravenous drug use, broad
      spectrum antibiotics, and indwelling central venous catheter is increasing. A 73
      year old man visited the outpatient clinic complaining of right shoulder pain
      that radiated to the right acromioclavicular joint. He had undergone multiple
      injection procedures followed by nonsteroidal anti-inflammatory drug therapy for
      several weeks. The ultrasonographic findings showed a heterogeneous mass around
      the right acromioclavicular joint, while the right shoulder MRI and the overall
      findings of the body bone scan were suggestive of osteomyelitis. Pathologic
      findings of ultrasonographically guided joint aspiration fluid showed acute and
      chronic nonspecific inflammation, while the tissue culture and staining revealed
      Candida parapsilosis.

PMID- 22977788
TI  - Rehabilitation for ataxia following chemotherapy for burkitt lymphoma involving
      the rectum.
AB  - Burkitt lymphoma is a type of B-cell lymphoma that occurs mostly in children, and
      rarely in adults. The sporadic type is known to occur mostly at the ileum and
      cecum. Cytarabine, which is used for central nervous system prophylaxis during
      chemotherapy for Burkitt lymphoma, has known neurotoxicity, and its side effects
      include motor ataxia due to cerebellar injury, ataxic dysarthria, dysfunction of
      ocular movement, confusion, somnolence and lethargy. This case report is about a
      patient diagnosed with Burkitt lymphoma who manifested motor ataxia after
      chemotherapy that included cytarabine.

PMID- 22977789
TI  - Meniscectomy.
AB  - To review the meniscus from a historical perspective especially on surgical
      management and general guidelines for arthroscopic meniscectomy procedures for
      various types of meniscal tears. We searched MEDLINE and PubMed for the years of
      1980-2010 using the terms meniscus, meniscal repair, menisectomy, and
      arthroscopy. Orthopedic surgeons frequently encounter patients with pain or
      functional impairment of the knee joint and repair or resection of the injured
      meniscus is one of the most common orthopedic operative procedures. The object of
      meniscal surgery is to reduce pain, restore functional meniscus and prevent the
      development of degenerative osteoarthritis in the involved knee. Historically,
      total meniscectomy was a common procedure performed for meniscus tear symptoms.
      However, it has been reported that total meniscectomy has deleterious effects on
      the knee. In the past, the menisci were thought as a functionless remnant tissue.
      Currently, it is known that the meniscus is an important structure for knee joint
      function. Menisci provide several vital functions including mechanical support,
      localized pressure distribution, and lubrication to the knee joint. It is widely
      accepted that the function of the meniscus can be preserved through minimal
      excision. An arthroscopic partial meniscectomy preserving more of the meniscus is
      preferred over total meniscectomy. In recent decades, this shift toward
      arthroscopic partial meniscectomy has led to the development of new surgical
      techniques.

PMID- 22977790
TI  - The tips and pitfalls of meniscus allograft transplantation.
AB  - When faced with an irrepairable meniscus or a patient who has had a total or
      subtotal meniscectomy, meniscus allograft transplantation (MAT) is the preferred
      modality to restore biomechanical function of the meniscus. The indications for
      meniscus allograft transplantation are yet to be established. However, currently,
      MAT has previously been indicated for symptomatic patients who have mild or early
      osteoarthritis, are younger than 50 years of age, and present with an Outerbridge
      grade II or lower. The short- to intermediate-term results confirmed noteworthy
      clinical improvements and consistent objective findings. On the other hand, the
      successful outcome would be reduced by various complications. Therefore, long
      term observation required to evaluate the longevity of these results. The purpose
      of this article is to review the current research of concerns on the results of
      MAT, and to describe the technical tips and pitfalls so as to successful clinical
      results.

PMID- 22977791
TI  - Relationship between Tibial Bone Defect and Extent of Medial Release in Total
      Knee Arthroplasty.
AB  - PURPOSE: To understand the relationship between tibial bone defect and extent of
      medial release in total knee arthroplasty. MATERIALS AND METHODS: We evaluated 32
      knees in 22 patients with variable degrees of tibial bone defect on medial
      plateau has undergone total knee arthroplasty. In this study, 31 cases had been
      diagnosed as degenerative osteoarthritis and 1 case was osteonecrosis. We
      excluded cases with infection, traumatic arthritis, or neuropathic joints. With
      regard to gender, 29 cases were female and 3 cases were male. The following
      relationships were analyzed: preoperative degrees of tibial bone defect and varus
      deformity; the femorotibial angle of both weight-bearing whole extremity
      radiogram, distractive stress radiogram, and the extent of medial release.
      RESULTS: Average tibial bone defect was 9.8+/-4.1 mm. Average femorotibial angle
      on weight-bearing whole extremity radiograph was varus 10.0 degrees +/-6.2
      degrees . Average femorotibial angle on distractive stress radiograph was varus
      0.7 degrees +/-4.6 degrees . Statistically the extent of medial release showed no
      significant relationship with the degree of tibial bone defect and femoro-tibial
      angle of whole extremity radiogram. However, it revealed a statistically
      significant relationship with the femorotibial angle on distractive radiogram
      (r=0.465, p=0.007). CONCLUSIONS: Preoperative distractive stress radiograph might
      be a useful method to predict the extent of intraoperative medial release during
      total knee arthroplasty.

PMID- 22977792
TI  - What symptoms are more important for korean patients in knee osteoarthritis?
      Development and validation of the korean knee score.
AB  - PURPOSE: The purpose of this study was to develop and validate a novel knee
      evaluation instrument, the Korean Knee Score (KKS), to reflect a floor life style
      with high knee flexion. In addition, we aimed to assess the importance of high
      knee flexion activity for Korean patients. MATERIALS AND METHODS: The KKS was
      developed following the guidelines of the International Society of Arthroscopy,
      Knee Surgery and Orthopaedic Sports Medicine. During development step, generated
      items were asked to 50 patients to determine importance and obtain an impact
      score for each item. A total of 634 patients were included in the validation
      survey. RESULTS: Forty one items were generated and impact scores of each item
      about floor life style were higher than other items. The KKS exhibited excellent
      reliability (intraclass correlation coefficient=0.931) and strong internal
      consistency (Cronbach's alpha=0.973). The content validity was good, with no
      ceiling or floor effect. The construct, convergent, and divergent validities were
      good. Moderate responsiveness was evident, with a standardized response mean of
      0.74. CONCLUSIONS: The KKS, has good validity, reliability, and responsiveness.
      The KKS includes items for floor life style, which are thought more important for
      Korean patients. The KKS can be used as a good evaluation questionnaire for
      Korean knee osteoarthritis patients.

PMID- 22977793
TI  - The Correlation between Posterior Tibial Slope and Maximal Angle of Flexion after
      Total Knee Arthroplasty.
AB  - PURPOSE: The purpose of this study was to evaluate the correlation between the
      posterior tibial slope and the maximal angle of flexion after total knee
      arthroplasty. MATERIALS AND METHODS: Seventy nine cases (63 patients, 60 females
      and 3 males), which received total knee arthroplasty with the Nexgen LPS system
      from Jan 2001 to Jan 2004, were enrolled. We divided all cases into two subsets
      in two ways. Firstly, group A (up to 10 degrees , 44 cases) and group B (over 10
      degrees , 35 cases) were divided according to the mean value of the postoperative
      posterior tibial slope. Secondly, group alpha (up to -4 degrees , 39 cases) and
      group beta (over -4 degrees , 40 cases) were divided according to the mean
      difference between the preoperative posterior tibial slope and the postoperative
      posterior tibial slope. We compared the maximal angle of flexion between group A
      and group B, group alpha and group beta, respectively. RESULTS: There was no
      significant difference between group A and group B, and also between group alpha
      and group beta in terms of maximal angle of flexion. CONCLUSIONS: There was no
      significant correlation between the postoperative posterior tibial solpe and the
      maximal angle of flexion.

PMID- 22977794
TI  - Therapeutic effects of mesenchymal stem cells and hyaluronic Acid injection on
      osteochondral defects in rabbits' knees.
AB  - PURPOSE: To evaluate the treatment results of intraarticular injection according
      to the frequency of hyaluronic acid with mesenchymal stem cells on the
      osteochondral defect of rabbits' medial femoral condyles. MATERIALS AND METHODS:
      A 5 mm diameter and 4 mm depth osteochondral defect was made on the medial
      femoral condyles of 18 rabbits, divided into six groups. One week after
      osteochondral defect, group B was injected intraarticularly with hyaluronic acid
      (HA), group C with mesenchymal stem cells (MSCs), and group D, E and F with both
      HA and MSCs. Group E and F received second HA injection a week after. Further,
      group F received third HA injection in the third week. RESULTS: In a macroscopic
      evaluation, groups B (6; range, 5-8), C (6; range, 6-7), D (7; range, 6-7), E
      (6.5; range, 6-8) and F (7.5; range, 6-8) showed statistically significant
      improvements in osteochondral defect healing, compared with that of group A (4;
      range, 3-5) (p=0.002). In histological evaluation, groups B (11.5; range, 11-13),
      C (13; range, 12-18), D (16; range, 13-18), E (17.5; range, 13-20), and F (19.5;
      range, 12-22) showed statistically significant differences in osteochondral
      defect healing, compared with group A (8; range, 6-9) (p=0.006). CONCLUSIONS: The
      intraarticular injections of MSCs or HA can play an effective role during the
      healing osteochondral defects in rabbits.

PMID- 22977795
TI  - Functional outcome of transphyseal reconstruction of the anterior cruciate
      ligament in skeletally immature patients.
AB  - PURPOSE: In anterior cruciate ligament (ACL) injury, conventional adult
      reconstruction techniques have to face the potential risk of growth disturbance
      or angular deformities in skeletally immature patients. The aim of this study was
      to evaluate the clinical outcomes of ACL reconstruction by conventional
      transphyseal tunnel technique. MATERIALS AND METHODS: On a retrospective basis,
      we reviewed 25 skeletally immature patients; all the patients showed skeletal
      maturity at last follow-up, and the mean age was 16.4 years. The average injury
      to surgery interval was 12.6 months. Clinical outcomes were assessed at a mean of
      74.4 months postoperatively using the Lysholm Knee Scoring Scale, the Tegner
      activity level, the International Knee Documentation Committee (IKDC), and plain
      radiographs. RESULTS: All the patients had undergone transphyseal reconstruction
      of ACL. The mean Lysholm score was 48.36 points preoperatively and 93.32 points
      postoperatively; the mean Tegner activity level was changed from 3.0 points to
      5.6 points. The mean IKDC level was categorized as C preoperatively and changed
      to A postoperatively. CONCLUSIONS: Our midterm outcome at an average 6 years
      after surgery was satisfactory without significant leg length discrepancies or
      abnormal alignment of the knee joint. Transphyseal reconstruction of ACL is a
      good treatment modality in the skeletally immature patient.

PMID- 22977797
TI  - The evolution of the conventional endoscope in an era of 3-dimensional
      technology.

PMID- 22977796
TI  - Measurement of Knee Morphometrics Using MRI: A Comparative Study between ACL
      Injured and Non-Injured Knees.
AB  - PURPOSE: The purpose of this study is to find out the differences of distal femur
      morphology between the anterior cruciate ligament (ACL)-injured and the non-ACL
      injured on an magnetic resonance imaging (MRI), and the difference of bone
      structure by gender. MATERIALS AND METHODS: MRI Measurements of notch width (NW),
      bicondylar width (BCW), medial condyle width (MCW), lateral condyle width (LCW),
      medial-to-lateral condyle ratio (M:L ratio), and notch entrance width (NE) were
      taken from 120 subjects with ACL injury and the other 106 subjects without ACL
      injury, by three independent observers, at two different times. The measured
      values from MRI figures between the ACL-injured and the non-ACL-injured were
      compared and analyzed, with consideration of the differences by gender. Both
      intra and inter-observer reliability were calculated. RESULTS: There were
      significant differences of NW, BCW, MCW, LCW and NE by gender (p<0.001). While NW
      and MCW in male group were different (p<0.001), NW, MCW, M:L ratio and NW index
      (NWI) in female group were significantly different (p<0.001) in the bone
      morphology between the ACL-injured and non-ACL-injured. The intra- and inter
      observer reliability was satisfying. CONCLUSIONS: If necessary to take an MRI,
      female patients with small NWI and NW injury should be carefully treated because
      of possibility of ACL injuries.

PMID- 22977798
TI  - Feasibility of obtaining quantitative 3-dimensional information using
      conventional endoscope: a pilot study.
AB  - BACKGROUND/AIMS: Three-dimensional (3D) imaging is gaining popularity and has
      been partly adopted in laparoscopic surgery or robotic surgery but has not been
      applied to gastrointestinal endoscopy. As a first step, we conducted an
      experiment to evaluate whether images obtained by conventional gastrointestinal
      endoscopy could be used to acquire quantitative 3D information. METHODS: Two
      endoscopes (GIF-H260) were used in a Borrmann type I tumor model made of clay.
      The endoscopes were calibrated by correcting the barrel distortion and
      perspective distortion. Obtained images were converted to gray-level image, and
      the characteristics of the images were obtained by edge detection. Finally, data
      on 3D parameters were measured by using epipolar geometry, two view geometry, and
      pinhole camera model. RESULTS: The focal length (f) of endoscope at 30 mm was
      258.49 pixels. Two endoscopes were fixed at predetermined distance, 12 mm
      (d(12)). After matching and calculating disparity (v2-v1), which was 106 pixels,
      the calculated length between the camera and object (L) was 29.26 mm. The height
      of the object projected onto the image (h) was then applied to the pinhole camera
      model, and the result of H (height and width) was 38.21 mm and 41.72 mm,
      respectively. Measurements were conducted from 2 different locations. The
      measurement errors ranged from 2.98% to 7.00% with the current Borrmann type I
      tumor model. CONCLUSIONS: It was feasible to obtain parameters necessary for 3D
      analysis and to apply the data to epipolar geometry with conventional
      gastrointestinal endoscope to calculate the size of an object.

PMID- 22977799
TI  - Endoscopic Approach via the Minor Papilla for the Treatment of Pancreatic Stones.
AB  - BACKGROUND/AIMS: We aimed to evaluate whether the advanced techniques have
      influenced the minor papilla approach. METHODS: We studied the success rate of
      guide wire insertion by using ordinary techniques and advanced techniques
      (rendezvous method and precut method) in 30 patients via the minor papilla. We
      compared the selection of the access routes between before (52 patients) and
      after (28 patients) the introduction of the Soehendra stent retriever. RESULTS:
      In 19 out of 30 patients (63%), guide wire insertion via the minor papilla could
      be achieved by using ordinary techniques. In total, the guide wire could be
      inserted in 27 patients (90%) by using the advanced techniques. Before
      introduction of the Soehendra stent retriever, the major papilla approach was
      chosen in 38 cases (73%), and the minor papilla approach in 14 cases (27%). After
      introduction of the Soehendra stent retriever, the major papilla approach was
      used in 26 cases (93%) and the minor papilla in 2 cases (7%). The frequency of
      selecting the minor papilla approach has significantly decreased (p<0.05).
      CONCLUSIONS: The advanced techniques have contributed to the improvement of
      endoscopic approaches via the minor papilla, and decreased the frequency of
      selecting the minor papilla approach.

PMID- 22977800
TI  - Ectopic pancreas bleeding in the jejunum revealed by capsule endoscopy.
AB  - Ectopic pancreas is defined as pancreatic tissue found outside the usual anatomic
      location. It is often found incidentally at different sites in the
      gastrointestinal (GI) tract. The incidence of ectopic pancreatic tissue in
      autopsy series is 1% to 2%, with 70% of the ectopic lesions found in the stomach,
      duodenum and jejunum. Although it is usually a silent anomaly, an ectopic
      pancreas may become clinically evident when complicated by inflammation,
      bleeding, obstruction or malignant transformation. We report a case of ectopic
      pancreas located in the jejunum and presenting as an obscure GI bleeding, which
      was diagnosed by capsule endoscopy.

PMID- 22977801
TI  - A case of giant inflammatory ileal polyp removed by double-balloon enteroscopy.
AB  - Inflammatory fibroid polyps are rare benign tumors of the GI tract, that commonly
      present with intestinal obstruction as a result of intussusceptions in the small
      bowel. A 39-year old man visited our clinic with an asymptomatic polypoid mass in
      the distal ileum that was identified on abdominal computed tomography for
      postoperative surveillance after total gastrectomy due to previously diagnosed
      early gastric cancer. Retrograde double-balloon enteroscopy was performed to
      diagnose the ileal mass and a complete resection of the polyp was performed using
      snare for polypectomy without complications. The final histological finding was
      an ileal inflammatory polyp. Balloon-assisted enteroscopy is a valuable modality
      to diagnose and treat small bowel lesions in lieu of surgical procedures in
      selected cases.

PMID- 22977802
TI  - Successful endoscopic decompression for intramural duodenal hematoma with gastric
      outlet obstruction complicating acute pancreatitis.
AB  - Non-traumatic intramural duodenal hematoma (IDH) with duodenal obstruction caused
      by acute pancreatitis is rare. Most patients with non-extensive hematoma show
      improvement with non-operative treatments. Percutaneous drainage or surgery may
      be necessary in cases with suspected malignancy, perforation, or intestinal tract
      obstruction. We present a case of IDH caused by acute pancreatitis that led to
      obstruction of the duodenum and an experience of successful endoscopic
      decompression of the hematoma.

PMID- 22977803
TI  - International digestive endoscopy network 2012: a patchwork of networks for the
      future.
AB  - This special September issue of Clinical Endoscopy will discuss various aspects
      of diagnostic and therapeutic advancement of gastrointestinal (GI) endoscopy,
      explaining what is new in digestive endoscopy and why international network
      should be organized. We proposed an integrated model of international conference
      based on the putative occurrence of Digestive Endoscopy Networks. In
      International Digestive Endoscopy Network (IDEN) 2012, role of endoscopy in
      gastroesophageal reflux disease and Barrett's esophagus, endoscopy beyond
      submucosa, endoscopic treatment for stricture and leakage in upper GI, how to
      estimate the invasion depth of early GI cancers, colonoscopy in inflammatory
      bowel disease (IBD), a look into the bowel beyond colon in IBD, management of
      complications in therapeutic colonoscopy, revival of endoscopic papllirary
      balloon dilation, evaluation and tissue acquisition for indeterminate
      biliopancreatic stricture, updates in the evaluation of pancreatic cystic
      lesions, issues for tailored endoscopic submucosal dissection (ESD), endoluminal
      stents, management of upper GI bleeding, endoscopic management of frustrating
      situations, small bowel exploration, colorectal ESD, valuable tips for
      frustrating situations in colonoscopy, choosing the right stents for endoscopic
      stenting of biliary strictures, advanced techniques for pancreaticobiliary
      visualization, endoscopic ultrasound-guided biliopancreatic drainage, and how we
      can overcome the obstacles were deeply touched. We hope that IDEN 2012, as the
      very prestigious endoscopy networks, served as an opportunity to gain some clues
      for further understanding of endoscopic technologies and to enhance up-and-coming
      knowledge and their clinical implications from selected 25 peer reviewed articles
      and 112 invited lectures.

PMID- 22977804
TI  - Sketch of international digestive endoscopy network 2012 meeting: overview.
AB  - International Digestive Endoscopy Network (IDEN) is an international meeting
      covering scientific subjects of diverse topics about upper gastrointestinal (GI)
      endoscopy, colonoscopy, endoscopic ultrasonography, and PB endoscopy. IDEN is
      organized by Korean Society of Gastrointestinal Endoscopy and the Korean
      Gastrointestinal Endoscopy Research Foundation, and took its first step in 2011
      in Seoul, Korea. IDEN inaugurated a new era of diagnostic and therapeutic GI
      endoscopy. IDEN 2012 was designed to offer participants from all over the world
      with opportunities to share up-to-date knowledge about basic and clinical aspects
      of GI endoscopy and to engage in in-depth discussion with worldwide well-known
      experts. During the 2 days of meeting, there were 62 invited lectures, 28 case
      based discussions, 20 video lectures, and 6 breakfast with the experts. There
      were a total of 598 participants registered from 12 countries, including Asian
      countries, Europe, and USA as well as Korea.

PMID- 22977805
TI  - Upper endoscopy in international digestive endoscopy network 2012: towards upper
      end of quality.
AB  - Upper gastrointestinal (GI) endoscopy is the most basic part of endoscopy field.
      Although old and basic procedures are still in use, a line of innovative
      techniques and devices are being introduced to allow much complex and difficult
      procedures in endoscopy unit. High quality upper endoscopic procedures can
      replace or obviate surgical treatment. Selected reviews dealing with non-variceal
      upper GI bleeding, challenging esophageal stenting, endoscopic management of
      subpeithelial tumor, and endoscopic evaluation for candidate lesions of
      endoscopic submucosal dissection were selected among the topics from
      International Digestive Endoscopy Network 2012.

PMID- 22977806
TI  - Management of non-variceal upper gastrointestinal bleeding.
AB  - Upper gastrointestinal bleeding (UGIB) is a critical condition that demands a
      quick and effective medical management. Non-variceal UGIB, especially peptic
      ulcer bleeding is the most significant cause. Appropriate assessment and
      treatment have a major influence on the prognosis of patients with UGIB. Initial
      fluids resuscitation and/or transfusion of red blood cells are necessary in
      patients with clinical evidence of intravascular volume depletion. Endoscopy is
      essential for diagnosis and treatment of UGIB, and should be provided within 24
      hours after presentation of UGIB. Pre-endoscopic use of intravenous proton pump
      inhibitor (PPI) can downstage endoscopic signs of hemorrhage. Post-endoscopic use
      of high-dose intravenous PPI can reduce the risk of rebleeding and further
      interventions such as repeated endoscopy and surgery. Eradication of Helicobacter
      pylori and withdrawal of non-steroidal anti-inflammatory drugs are recommended to
      prevent recurrent bleeding.

PMID- 22977807
TI  - New endoscopic hemostasis methods.
AB  - Endoscopic treatment for non-variceal upper gastrointestinal bleeding has evolved
      over decades. Injection with diluted epinephrine is considered as a less than
      adequate treatment, and the current standard therapy should include second
      modality if epinephrine injection is used initially. Definitive hemostasis rate
      following mono-therapy with either thermo-coagulation or hemo-clipping compares
      favorably with dual therapies. The use of adsorptive powder (Hemo-spray) is a
      promising treatment although it needs comparative studies between hemospray and
      other modalities. Stronger hemo-clips with better torque control and wider span
      are now available. Over-the-scope clips capture a large amount of tissue and may
      prove useful in refractory bleeding. Experimental treatments include an
      endoscopic stitch device to over-sew the bleeding lesion and targeted therapy to
      the sub-serosal bleeding artery as guided by echo-endoscopy. Angiographic
      embolization of bleeding artery should be considered in chronic ulcers that fail
      endoscopic treatment especially in elderly patients with a major bleed manifested
      in hypotension.

PMID- 22977808
TI  - How can we maximize skills for non-variceal upper gastrointestinal bleeding:
      injection, clipping, burning, or others?
AB  - Endoscopy has its role in the primary diagnosis and management of acute non
      variceal upper gastrointestinal bleeding. Main roles of endoscopy are identifying
      high risk stigmata lesion, and performing endoscopic hemostasis to lower the
      rebleeding and mortality risks. Early endoscopy within the first 24 hours enables
      risk classification according to clinical and endoscopic criteria, which guide
      safe and prompt discharge of low risk patients, and improve outcomes of high risk
      patients. Techniques including injection therapy, ablative therapy and mechanical
      therapy have been studied over the recent decades. Combined treatment is more
      effective than injection treatment, and single treatment with mechanical or
      thermal method is safe and effective in peptic ulcer bleeding. Specific treatment
      and correct decisions are needed in various situations depending on the site,
      location, specific characteristics of lesion and patient's clinical conditions.

PMID- 22977809
TI  - Esophageal stent for cervical esophagus and esophagogastric junction.
AB  - Tumors in the cervical portion of the esophagus have traditionally been more
      difficult to manage. The implantation in the cervical esophagus is a technically
      demanding procedure. The implantation of modified self-expandable metal stents
      (SEMSs) was very effective perorally under endoscopic and fluoroscopic guidance.
      Experience with SEMS has revealed an increased risk of migration when either
      covered stents are used or a stent is implanted across the gastroesophageal
      junction. The modified, covered, esophageal stents appear to prevent stent
      migration and improve dysphagia in patients with malignant tumor stenosis at the
      esophagogastric junction. Besides heartburn, regurgitation is sometimes very
      distressing to patients and may lead to fatal aspiration due to reflux after
      stenting in esophagogastric junction. These symptoms can be reduced by the use of
      valved stent. The long S-shape valve is very effective in preventing acid reflux
      and valve inversion.

PMID- 22977810
TI  - Endoscopic resection of subepithelial tumors.
AB  - Subepithelial tumors (SETs) are often incidentally found during endoscopic
      examinations. Endoscopic ultrasonography (EUS) is a good method for differential
      diagnosis of SETs, but a definite diagnosis cannot be made based on EUS features
      alone in some cases. Periodic follow-up examinations by endoscopy and EUS remains
      the recommended management strategy, which involves issues related to patient
      compliance, cost-effectiveness, and the risk associated with repeated endoscopic
      procedures and delayed diagnosis of malignancy. Endoscopic resection of the SETs
      is another technique to treat them as well as to obtain tissue specimens for
      accurate histologic diagnosis. Herein, a various endoscopic techniques ranging
      from simple snare resection to endoscopic submucosal tunnel dissection for the
      management of SETs will be reviewed.

PMID- 22977811
TI  - Estimation by gross findings in early gastric cancer.
AB  - Endoscopic resection has been accepted as both minimally invasive and curative
      treatment modality for early gastric cancer (EGC). The widely accepted indication
      of endoscopic resection for EGC is small sized, differentiated mucosal cancer in
      which the risk of lymph node metastasis is negligible. Tumor size can be measured
      by conventional endoscopy, and chromoendoscopy, magnifying endoscopy, narrow band
      imaging, autofluorescence imaging can also be helpful for accurate estimation of
      tumor size. Pretreatment tumor histology can be assessed with endoscopic biopsy,
      and also be measured by confocal endomicroscopy (so called "virtual biopsy").
      Although endoscopic ultrasonography may be helpful for the assessment of tumor
      depth in EGC, the accurate assessment of tumor depth can be performed by the
      typical findings in the conventional endoscopy, by which treatment modality can
      be decided according to the depth of tumor invasion.

PMID- 22977812
TI  - International digestive endoscopy network to strengthen network for lower
      gastrointestinal diseases including inflammatory bowel disease and colorectal
      cancer.
AB  - The International Digestive Endoscopy Network 2012 organized by Korean Society of
      Gastrointestinal Endoscopy was held at Seoul, Korea on June 9 to 10, 2012, during
      which invited lectures of world renowned experts on the lower gastrointestinal
      (GI) tract were given with a wide range of the latest knowledge and novel imaging
      of inflammatory bowel disease (IBD) and colorectal endoscopic submucosal
      dissection (ESD). There were very informative five sessions in the lower GI part
      consisting of: Colonoscopy in IBD; what can we do in 2012?; A look into the bowel
      beyond colon in IBD; How to estimate the invasion depth of early GI cancer?; No
      more no man's land: small bowel exploration; and colorectal ESD: can it be a
      popular procedure?

PMID- 22977813
TI  - Differential diagnosis of inflammatory bowel disease: what is the role of
      colonoscopy?
AB  - Colonoscopy plays a crucial role in the diagnosis, treatment and follow-up
      monitoring of inflammatory bowel disease (IBD). Practitioners should be well
      informed of the colonoscopic findings of IBD to prevent the misdiagnosis,
      overtreatment or delayed treatment. Distinguishing between Crohn's disease and
      ulcerative colitis is essential in terms of pharmacological treatment, surgical
      decision-making, and prognosis. But there are still lesions with difficulty in
      differentiation that approximately 10% of the patients fall into the category of
      indeterminate colitis. Efforts are needed to carefully select treatment approach
      appropriate for each patient by providing a precise diagnosis on the extent and
      degree of lesions as well as to accurately delineate the lesions to assure that
      they are compared in subsequent rounds of follow-up monitoring in order to allow
      redetermination and adjustment of the treatment.

PMID- 22977814
TI  - A look into the small bowel in Crohn's disease.
AB  - Crohn's disease (CD) is an inflammatory bowel disease that can affect the entire
      gastrointestinal tract, with the small bowel (SB) being the most commonly
      affected site. In some patients, refractory inflammation or chronic strictures of
      the SB are responsible for a debilitating course of the disease that might lead
      to severely reduced quality of life. Therefore, SB imaging is a crucial element
      in diagnosing and/or managing SB CD, and continues to evolve because of
      technologic advances. SB endoscopy (capsule endoscopy and device-assisted
      enteroscopy) and cross-sectional radiologic imaging (computed tomography
      enterography and magnetic resonance enterography) have become key players to
      diagnose and/or manage CD. In everyday practice, the choice of the imaging
      modalities is based on the presence and availability of the techniques and of
      experienced operators in each institute, clinical usefulness, safety, and cost.
      Here, SB endoscopy and radiologic imaging in suspected or known CD patients will
      be addressed and discussed.

PMID- 22977815
TI  - Role of computed tomography enterography/magnetic resonance enterography: is it
      in prime time?
AB  - Today, cross-sectional imaging modalities, such as computed tomography
      enterography (CTE) and magnetic resonance enterography (MRE), are particularly
      suited to evaluate small bowel diseases, especially Crohn's disease (CD). It is
      well known that CTE/MRE can provide excellent assessment of disease activity as
      well as the macroscopic features, extramural abnormalities, and complications of
      the small intestine in patients with CD. In general, CTE is considered as the
      first-line modality for the evaluation of suspected inflammatory bowel disease
      and for long-term assessment or follow-up of these patients. Because of the
      advantage of lack of radiation, MRE is being used more frequently, especially in
      children or young patients with CD.

PMID- 22977816
TI  - Colonoscopic Cancer Surveillance in Inflammatory Bowel Disease: What's New Beyond
      Random Biopsy?
AB  - Colonoscopy based colitis surveillance is widely accepted to try to prevent
      development of and ensure early detection of colitis-associated colorectal
      cancer. Traditionally this has been performed with quadrantic random biopsies
      throughout the colon. Chromoendoscopy "dye-spray" with targeted biopsies only has
      been shown to increase dysplasia detection 4 to 5 fold on a per lesion basis. It
      has therefore been suggested that random biopsies should be abandoned as they do
      not increase dysplasia detection nor change patient clinical course. Recent
      British guidelines for colitis surveillance have strongly endorsed
      chromoendoscopy. This short review summarizes current international guidelines
      and looks at how to optimize white light colonoscopy in colitis considering:
      bowel preparation, withdrawal time, high definition, and structure enhancement.
      Data for advanced imaging techniques are reviewed including positive evidence in
      favor of chromoendoscopy, and limited data suggesting autofluoresence imaging may
      be promising. Narrow band imaging does not increase dysplasia detection in
      colitis. Confocal endomicroscopy might potentially reduce biopsies beyond that of
      chromoendoscopy but does not offer a clear detection advantage. Pan-colonic
      chromoendoscopy with targeted biopsies increases dysplasia detection and is the
      standard of care in the United Kingdom. It is likely that the use of
      chromoendoscopy for colitis surveillance will become widely accepted
      internationally.

PMID- 22977817
TI  - How do I overcome difficulties in insertion?
AB  - Demand for colonoscopy is increasing because it is an important tool not only for
      screening of colorectal neoplasm but also for resection of such lesions in early
      stage. Cecal intubation requires expertise on shortening of the examination time
      and improvement of the cecal intubation rate without causing pain to the
      patients. About 5% to 10% of patients still experience difficulties or failure of
      the cecal intubation. There are number of factors that affect the difficulty of
      the colonoscopy such as technical skill of the endoscopist, angulated sigmoid,
      redundant colon, advanced age, female gender, diverticular disease, and
      inadequate bowel preparation. In an effort to overcome these situations and to
      and aiding colonoscope insertion with reducing pain, various methods have
      introduced. Like this review discusses ways to approach patients with technically
      difficult colons for achieving the successful cecal intubation.

PMID- 22977818
TI  - How do I manage post-polypectomy bleeding?
AB  - Colonoscopic polypectomy is an effective method for prevention of colorectal
      cancer and has become one of the most common procedures worldwide. Most
      colorectal polyps can be removed safely by various polypectomy techniques;
      however, serious complications can occur. Postpolypectomy bleeding is the most
      common complication of colonoscopic polypectomy, accounting for 0.3% to 6.1% of
      polypectomy. This issue summarizes various endoscopic techniques to treat
      postpolypectomy bleeding.

PMID- 22977819
TI  - Indications, Knives, and Electric Current: What's the Best?
AB  - Endoscopic submucosal dissection (ESD) was developed to overcome the limitations
      of conventional endoscopic mucosal resection (EMR), and ESD has been also applied
      for large colorectal neoplasms. Since colorectal ESD is still associated with
      higher perforation rate, a longer procedure time, and increased technical
      difficulty, the indications should be strictly considered. Generally, colorectal
      tumors without deep submucosal invasion or minimal possibility of lymph node
      metastasis, for which en bloc resection using conventional EMR is difficult, are
      good candidates for colorectal ESD. The ideal knife for colorectal ESD should
      avoid making perforations but can make a clean cut of optimal depth at one time.
      The ideal current for ESD differs depending on the procedure used, the surgical
      devices used, the tissue to be dissected, and the operator's preference.
      Application of the optimal indications and improvements in the technical skill
      and surgical devices are required for easier and safer colorectal ESD.

PMID- 22977820
TI  - Current status of colorectal endoscopic submucosal dissection in Korea.
AB  - Colorectal endoscopic submucosal dissection (ESD) is not yet fully popularized in
      Korea, but is increasing steadily. The outcomes of colorectal ESD in Korea are
      comparable to those in Japan and other countries. ESD-related complication rates
      are decreasing as experiences accumulate. Particularly for rectal laterally
      spreading tumors, ESD is becoming more prevalent than transanal endoscopic
      microsurgery. Standard indication, qualified training system, and full medical
      insurance coverage should be established for the procedure to become popular in
      the long run.

PMID- 22977821
TI  - Lessons from korean capsule endoscopy multicenter studies.
AB  - Since its development, video capsule endoscopy (VCE) introduced a new area in the
      study of small bowel disease. We reviewed and discussed current issues from
      Korean capsule endoscopy multicenter studies. Main results are as follows: First,
      there was no significant difference in diagnostic yield according to the method
      of bowel preparation. Second, VCE represents a reliable and influential screening
      measure in patients with chronic unexplained abdominal pain and this technique
      could successfully alter the clinical course especially for patients with small
      bowel tumor. Third, the inter-observer variation in the expert group was lower
      than that in trainee group. Fourth, studies about the spontaneous capsule passage
      after retention showed 2.5% of retention rate and the size of lumen was an
      important factor of spontaneous passage. We need larger scale studies on the
      effect of bowel preparation methods on the diagnostic yield and further studies
      about the learning curve or unique capsule endoscopic findings for small
      intestinal diseases in Korean patients.

PMID- 22977822
TI  - Highlights of pancreatobiliary endoscopy in international digestive endoscopy
      network 2012: how much has it advanced?
AB  - The pancreatobiliary organ is composed of one of the most complicated structures
      and complex physiological functions among other digestive organs in our body.
      This is why endoscopic procedure in pancreaticobiliary system requires rather
      complicated techniques. In International Digestive Endoscopy Network (IDEN) 2012,
      many interesting pancreatobiliay endoscopy related topics were presented. Basic
      procedures like endoscopic papillary balloon dilation (EPBD), advanced techniques
      like endoscopic necrosectomy, prevention and management of post-ERCP
      pancreatitis, and spyglass system are reviewed in this highlight summary.

PMID- 22977823
TI  - Endoscopic papillary large balloon dilation: guidelines for pursuing zero
      mortality.
AB  - Since endoscopic papillary large balloon dilation (EPLBD) is used to treat benign
      disease and as a substitute for conventional methods, such as endoscopic
      sphincterotomy plus endoscopic mechanical lithotripsy, we should aim for zero
      mortality. This review defines EPLBD and suggests guidelines for its use based on
      a review of published articles and our large-scale multicenter retrospective
      review.

PMID- 22977824
TI  - Prevention and management of post-endoscopic retrograde cholangiopancreatography
      complications.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is associated with a
      spectrum of complications such as pancreatitis, hemorrhage, perforation, and
      cardiopulmonary events. These complications can range from mild to severe
      resulting in extended hospitalization, requiring surgical intervention, and
      leading to permanent disability or even death. Complications of ERCP have been
      better understood in the past decade, with adoption of standardized consensus
      based definitions of complications and introduction of new recommendations to
      minimize risks of ERCP. Adequate selection of patients undergoing ERCP, skilled
      operators using novel techniques and prompt identification and treatment are key
      to successful prevention and management.

PMID- 22977825
TI  - Endoscopic necrosectomy for walled-off pancreatic necrosis.
AB  - Approximately 20% of patients with acute pancreatitis develop pancreatic necrosis
      with significant mortality. Surgical debridement is the traditional management of
      necrotizing pancreatitis, but it is associated with significant morbidity and
      mortality. Endoscopic necrosectomy using repeats session of debridement and stent
      insertion has been more frequently used within the last decade and half. This
      technique continues to evolve as we attempt to optimize the post-procedural
      outcomes.

PMID- 22977826
TI  - Spyglass direct visualization system.
AB  - Although endoscopic retrograde cholangiopancreatography is considered the gold
      standard to manage biliary disorders, it has its own limitations. The single
      operator cholangioscopy (SOC) system (Spyglass) may offer an interesting
      compromise for most advanced biliary endoscopists, in terms of size (10 Fr
      diameter) and complexity of use. SOC is a great step toward intraductal
      visualization and therapy but the best is yet to come.

PMID- 22977827
TI  - Endoscopic ultrasound, where are we now in 2012?
AB  - Topics related with endoscopic ultrasound (EUS) made up considerable portion
      among many invited lectures presented in International Digestive Endoscopy
      Network 2012 meeting. While the scientific programs were divided into the fields
      of upper gastrointestinal (UGI), lower gastrointestinal, and pancreato-biliary
      (PB) categories, UGI and PB parts mainly dealt with EUS related issues. EUS
      diagnosis in subepithelial lesions, estimation of the invasion depth of early
      gastrointestinal cancers with EUS, and usefulness of EUS in esophageal varices
      were discussed in UGI sessions. In the PB part, pancreatic cystic lesions, EUS
      guided biliopancreatic drainage, EUS-guided tissue acquisition, and improvement
      of diagnostic yield in indeterminate biliary lesions by using intraductal
      ultrasound were discussed. Advanced techniques such as contrast-enhanced EUS, EUS
      elastography and forward-viewing echoendoscopy were also discussed. In this
      paper, I focused mainly on topics of UGI and briefly mentioned about advanced EUS
      techniques since more EUS related papers by other invited speakers were presented
      afterwards.

PMID- 22977828
TI  - Usefulness of endoscopic ultrasound in esophagogastric varices.
AB  - Endoscopic ultrasound (EUS) is a useful diagnostic tool for evaluation of
      esophagogastric varices and guidance of endoscopic therapy. EUS can visualize not
      only collateral veins around the esophagus but also perforating veins that
      connect esophageal varices with collateral veins. They are associated with high
      risk of bleeding and early recurrence after initial variceal eradication.
      Isolated gastric varices can be easily diagnosed using EUS that mimic thickened
      gastric folds or subepithelial tumors. EUS-guided endoscopic therapy is a
      challenging field of variceal bleeding. It has a potential role for assistance of
      interventions and evaluation of treatment outcome.

PMID- 22977829
TI  - Endoscopic ultrasonography in the evaluation of indeterminate biliary strictures.
AB  - Biliary strictures may be due to a variety of benign and malignant processes.
      Imaging with endoscopic ultrasonography (EUS) often suggests the diagnosis, but
      is usually not definitive. EUS-guided fine needle aspiration (FNA) facilitates
      the diagnosis of extrahepatic biliary strictures, although peritioneal metastases
      due to needle tract seeding may occur after EUS-FNA of cholangiocarcinoma. In
      addition to diagnosis of strictures, EUS may play an important role in staging of
      cholangiocarcinoma.

PMID- 22977830
TI  - Usefulness of Intraductal Ultrasonography in the Diagnosis of Cholangiocarcinoma
      and IgG4-Related Sclerosing Cholangitis.
AB  - The technique of intraductal ultrasonography (IDUS) of the bile duct with a thin
      caliber probe and a ropeway system has provided excellent images of the bile duct
      and periductal structures and is an easy transpapillary approach. In addition,
      once the guide wire is inserted into the bile duct, IDUS and transpapillary
      biopsy after endoscopic retrograde cholangiopancreatography can be performed in a
      single session. Here, we review the usefulness of IDUS in the diagnosis of
      cholangiocarcinoma and IgG4-related sclerosing cholangitis.

PMID- 22977831
TI  - Endoscopic Ultrasound-Guided Drainage of Pancreatic Fluid Collections (with
      Video).
AB  - Endoscopic ultrasound (EUS) is often used to guide drainage of pancreatic fluid
      collections (PFCs). EUS enhances the diagnosis of cystic pancreatic lesions and
      enables real-time image-guided control of PFC drainage. EUS may facilitate the
      endoscopic treatment of patients with pancreatic necrosis and patients with
      disconnected pancreatic duct syndrome.

PMID- 22977832
TI  - No Place Like Home: Examining a Bilingual-Bicultural, Self-Run Substance Abuse
      Recovery Home for Latinos.
AB  - Latinos often do not seek substance abuse services, and this might be correlated
      to the lack of culturally-modified substance abuse treatment approaches. Oxford
      House is the largest self-help residential recovery program in the U.S., yet few
      Latinos are among their current residents. In an effort to change this, bilingual
      bicultural recovery homes were recently developed for Latinos. This article
      describes the process in opening these bilingual-bicultural houses and how
      sociocultural factors such as the family, simpatia, and gender roles impacted the
      living environment of these houses. In addition, language is highlighted as a key
      factor to the comfort and success of Latinos living in Oxford Houses. Based on
      these experiences, the article addresses several obstacles/barriers that impacted
      this process and possible feasible solutions to these challenges. One challenge
      is the Latino family system. While this may provide a supportive, cost-effective
      option for some; it can also perpetuate a cycle of codependence and substance
      abuse.

PMID- 22977833
TI  - Facilitation of neurotransmitter release in mouse motor synapses in different
      modes of protein kinase C activation.
AB  - Protein kinase C blocker chelerythrine prevented the increase in quantal content
      of single and rhythmic evoked end-plate potentials after disinhibition of L-type
      Ca(2+)-channels with paxillin. Phorbol ester increased quantal content of single
      end-plate potentials and changed rhythmic activity of mouse motor synapses. The
      effects of phorbol ester were to a great extent neutralized by L-type Ca(2+)
      channel blocker nitrendipine and were completely abolished by K(+)-channel
      blocker 4-aminopyridine. Thus, we discovered different facilitations of
      transmission after protein kinase C activation with calcium current through L
      type channels and with phorbol ester.

PMID- 22977834
TI  - Peculiarities of sensory support of psychomotor activity that requires visual
      attention.
AB  - Stable correlations between correction task characteristics and components of
      visual evoked potentials in response to light flash have been revealed. Faster
      task performance in males in comparison with females was established to be
      attained due to effective tuning and attuning of visual-motor system at the
      levels of specific and nonspecific systems related to visual analyzer. This
      determines potential for monotonous activity requiring constant visual attention.

PMID- 22977835
TI  - Cholinergic receptor exocytosis under conditions of depression of acetylcholine
      induced current in edible snail neurons in cellular analogue of habituation.
AB  - Exocytosis inhibitor Exo 1 potentiates depression of acetylcholine-induced inward
      current in defensive behavior command neurons of edible snail, when acetylcholine
      is applied rhythmically to the soma in cellular correlate of habituation. A
      mathematical model presupposing different receptor localization in the cell and
      regularities of their translocations made it possible to analyze the dependence
      of acetylcholine-induced current depression on a number of intracellular
      processes. It was concluded that depression of choline-sensitive extrasynaptic
      zones on the membrane of defensive behavior command neurons in edible snail in
      cellular correlate of habituation is partially determined by attenuation of
      exocytosis of internalized cholinergic receptors.

PMID- 22977836
TI  - Mechanisms of maladaptation to physical exercise in Moscow schoolchildren.
AB  - Schoolchildren overloaded with learning do not have time to exercise and often
      have hypodynamia. Namely they show primarily such negative effects of hypokinesia
      as incorrect posture, insufficient muscular development, and obesity. Lack of
      physical activity has acute effect on the formation of the cardiovascular system
      in schoolchildren. Here we assess the level of physical development and the
      degree of adaptation to physical exercise in schoolchildren of different age and
      gender.

PMID- 22977837
TI  - Study of proliferative processes and nuclear estradiol and progesterone receptors
      in myocytes in pregnant and postpartum mouse uterus.
AB  - Numerical densities of the nuclei were morhometrically evaluated in all myocytes
      and myocytes expressing nuclear estrogen- and progesterone-receptor complexes,
      which were revealed immunohistochemically with monoclonal antibodies in C57Bl/6
      mice. It was shown that the above quantitative parameters of myometrial cells
      after the first pregnancy were similar to those in nonpregnant mice by day 10
      after delivery. In the third pregnancy, especially developed after the second
      interrupted pregnancy, proliferation processes in the myometrium were not
      completed by postpartum day 10, but dramatically progressed. It was associated
      with a significant decrease in the fraction of myocytes carrying nuclear hormone
      receptor complexes with estradiol and progesterone and their disturbed
      physiological relations in the myometrium during and after pregnancy probably due
      to dedifferentiation of a considerable part of myocytes.

PMID- 22977838
TI  - Assessment of intramural blood flow and neurogenic control in intact and
      hypertrophic urinary bladder with harmonic analysis of bioimpedance in rats.
AB  - High-resolution impedancometry and harmonic (Fourier) analysis of variable
      component of bioimpedance revealed rhythmic oscillations of urinary bladder
      bioimpedance at the Mayer wave, respiration, and heartbeat frequencies. The power
      values of the corresponding Mayer, respiratory, and cardiac peaks were calculated
      to assess circulation in the urinary bladder wall and its autonomic nervous
      control at various stages of infusion cystometry in intact rats and in the rats
      with preliminary formed infravesical obstruction (IVO). In intact rats, filling
      of the bladder with physiological saline diminished the power of the first
      (fundamental) cardiac peak attesting to a decrease of the blood flow in the
      bladder wall. Simultaneously, the power of low-frequency Mayer peak reflecting
      sympathetic activity increased, while the power of respiratory peak decreased
      supposedly reflecting abatement of the parasympathetic influences. Bladder
      voiding was accompanied by a decrease of Mayer peak and increase of the
      respiratory one. Prior to infusion cystometry, the intravesical pressure in IVO
      rats was elevated while the power of fundamental cardiac peak was below the
      control value. Filling the bladder in these rats was accompanied by further
      decrease of the cardiac peak reflecting still greater drop in blood supply. In
      control rats, voiding the bladder normalized the vesical circulation assessed by
      the cardiac peak, while in IVO rats this peak remained decreased. The reciprocal
      changes of Mayer and respiratory peaks observed during infusion cystometry in the
      norm were replaced by unidirectional decrease in the power of both peaks in IVO
      rats, which probably attest to disturbance of autonomic nervous control in the
      hypertrophic urinary bladder in these rats.

PMID- 22977839
TI  - Lymphostimulating activity of agents used in lung pathologies.
AB  - Lymphostimulating effects of antibiotics and diuretics most commonly used in
      pulmonology were investigated under conditions of intravital biomicroscopy of the
      small intestinal mesenterium in rats. Results of the study demonstrated weak or
      no activation of lymph circulation under the influence of the test agents in
      comparison with direct-action peptide lymphostimulators.

PMID- 22977840
TI  - Endogenous regulators of NO bioavailability in rats with acute renal failure.
AB  - We studied the impact of acute glycerol-induced renal failure on blood levels and
      daily urinary excretion of arginine, monomethylarginine, and asymmetric and
      symmetric dimethylarginine. Acute renal failure was accompanied by enhanced daily
      excretion of asymmetric and symmetric dimethylarginine, increased plasma level of
      symmetric dimethylarginine, and decreased plasma level of arginine. Reabsorption
      of arginine and its methylated analogues decreased, thus compensating for reduced
      glomerular filtration rate. These data attest to increased production of
      dimethylarginines during acute renal failure. These changes can decrease NO
      bioavailability.

PMID- 22977841
TI  - Prolactine receptor expression in kidney tissue of female rats with cholestasis:
      the effect of hyperprolactinemia.
AB  - Immunohistochemistry with semiquantitative image analysis showed that prolactin
      receptor in distal renal tubules of female rats is most sensitive to the negative
      effects of both cholestasis and hyperprolactinemia. The responses of medullary
      tubules to cholestasis and hyperprolactinemia were less pronounced: decrease and
      increase in prolactin receptor expression, respectively. Proximal tubules were
      characterized by stable levels of prolactin receptor expression insensitive to
      the effects of obstructive cholestasis and hyperprolactinemia. The cholestasis
      induced changes in the intensity of prolactin receptor expression were opposite
      in kidney and liver cells. It is concluded that different parts of the nephron
      differ by the presence, type, and direction of regulation of prolactin receptor
      expression in obstructive cholestasis and hyperprolactinemia.

PMID- 22977842
TI  - Lymph and blood cytokines in fever of different severity.
AB  - Experiments on rats showed that pyrogenal-induced fever is associated with
      elevation of IL-1beta, IL-6, and IL-10 content in the thoracic duct lymph and
      blood plasma, whereas low-grade fever induced by administration of Freund's
      complete adjuvant is associated with elevation of only IL-6 concentration. The
      increase in IL-1beta concentration during fever and IL-6 concentration in both
      processes was more pronounced in the central lymph than in blood plasma.
      Unchanged concentrations of IL-1beta and IL-10 in low-grade fever apparently
      reflect differences in the mechanisms of these pathological processes.

PMID- 22977843
TI  - Effects of physicochemical forms of phenazepam and Panavir on their action at
      ultra-low doses.
AB  - A concept of physicochemical forms of biologically active substances introduced
      in investigation of the action mechanism of ultra-low doses allows qualitative
      explanation of the main effects of ultra-low doses, chemical diversity of
      biologically active substances, and physical boundaries for these effects.
      Phenazepam was shown to possess activity in ultra-low doses only in disperse
      state, in the form of nanoparticles with a diameter <100-300 nm; these
      nanoparticles appear as micelles of surface active substances and solvated.
      Panavir possesses pharmacological activity in ultra-low doses and appears as
      nanoparticles with a diameter of 200-300 nm, which have uncompensated negative
      surface charge and polymer nature.

PMID- 22977844
TI  - Biochemical indicators of atherogenic and protective activity of xydiphone in
      experimental animals.
AB  - Atherosclerotic plaque formation and vascular calcinosis were modeled in a
      subchronic experiment. Reduced HDL and elevated LDL concentrations, increased
      atherogenic index and albumin toxicity index, and high blood levels of
      triglycerides and uric acid were early markers of pathology. Xydiphone in
      combination with vitamin D effectively reduced these changes and the degree of
      vascular calcinosis.

PMID- 22977845
TI  - Studies of oxidant-induced changes in albumin transport function with a
      fluorescent probe K-35. Metal-catalyzed oxidation.
AB  - The dynamics of albumin transport function was studied during metal-catalyzed
      oxidation of albumin in diluted blood plasma from healthy donors and in the
      solution of purified albumin using fluorescent probe K-35. The changes were
      compared with the dynamics of free radical oxidation markers. For oxidation,
      different concentrations of Cu(2+), Fe(2+), Fe(3+) ions as well as EDTA and
      H(2)O(2) were used. Oxidative modification of proteins was assessed by carbonyl
      and bityrosine fluorescent products. Oxidation of plasma lipids was assessed by
      the levels of TBA-reactive products. It was found that oxidation markedly
      decreased effective concentration of albumin characterizing albumin binding
      capacity, and leads to accumulation of carbonyl products of protein oxidation,
      bityrosine fluorescent products in proteins, and TBA-active products of lipid
      oxidation. It was hypothesized that reduced effective concentration of albumin is
      related to impairment of its binding sites and/or accumulation of free-radical
      oxidation products filling the binding sites of albumin.

PMID- 22977846
TI  - Experimental study of antinociceptive potency of dipeptide GB-115 during chemical
      and thermal stimulation.
AB  - The study examined the antinociceptive potency of dipeptide compound GB-115
      (amide N-6-phenylhexanoyl-glycyl-L-tryptophan) during thermal and chemical
      noxious stimulation of mice. Peroral administration of GB-115 (0.1-20 mg/kg)
      decreased the incidence of abdominal contractions induced with intraperitoneal
      acetic acid (0.75%). This effect was comparable to that of sodium diclofenac (20
      mg/kg); it was only partially antagonized with naloxone indicating the presence
      of significant non-opioid component in analgesic effect of GB-115. Ability of
      this dipeptide to moderate the nociceptive response in tail flick test under a
      non-selective blockade of the opioid receptors with naloxone and the absence of
      similar analgesic potency assessed in the hot plate test attest to predominant
      effect of GB-115 on spinal opioid receptors.

PMID- 22977847
TI  - Effect of NF-kappaB inhibitor aurothiomalate on local inflammation in
      experimental Th1- and Th2-type immune response.
AB  - We compared the effect of NF-kappaB inhibitor aurothiomalate and voltaren on
      local inflammation in different types of immune response. Both substances reduced
      edema caused by sheep erythrocytes (Th1-type immune response) and local immediate
      type hypersensitivity response induced with ovalbumin (Th2-dependent response).
      The anti-inflammatory effects of aurothiomalate were similar to those of voltaren
      during Th1-type immune response.

PMID- 22977848
TI  - Pharmacokinetics of liposomal gentamicin.
AB  - We present data on pharmacokinetics of free and liposomal forms of gentamicin.
      Comparative study of two drug forms showed that immobilization of gentamicin in
      liposomes significantly increased most important pharmacokinetic parameters of
      the antibiotic (AUC, Cmax, MRTpo, T(1/2), Kel, Vzpo) and reduced Clpo and Kel.

PMID- 22977849
TI  - Effects of dexamethasone on the development of neonatal rats and level of active
      caspase-3 in brain cortex.
AB  - Dexamethasone increased the levels of active caspase-3 form in the brain cortex
      of neonatal rats 120 h after drug administration, but did not affect the
      expression of this key apoptotic protease in the brain 6 or 24 h postinjection.
      Increased expression of the active form of caspase-3 in the cerebral cortex was
      associated with earlier eye opening and delayed formation of startle-reflex in
      rats.

PMID- 22977850
TI  - Excretion of himantane and its metabolites with the urine and feces in rats.
AB  - The levels of himantane and its metabolites in daily urine and feces of rats were
      measured after intraperitoneal and oral dose of 25 mg/kg. The injected dose of
      the initial substance and 1.3% its metabolites were eliminated with excrements
      within 24 h after administration via both routes 0.23%.

PMID- 22977851
TI  - Effect of metabotropic receptor agonists on ionic current of snail neurons.
AB  - The dose-dependent and reversible changes of sodium (I(Na)), calcium (I(ca)),
      slow potassium (I(Ks)), and fast potassium (I(Kf)) currents were recorded in
      isolated snail neurons under the action of kappa-opioid agonist butorphanol and
      chemical agent RU-1203 applied in a concentration range of 1-1000 MUM.

PMID- 22977852
TI  - A new activity of N-cholinolytic drug benzohexonium.
AB  - We have found that N-cholinolytic drug benzohexonium produces a hypolipidemic
      effect: it reduces dyslipoproteinemia, fatty infiltration of the liver, and risk
      of atherosclerotic lesions.

PMID- 22977853
TI  - Vascularization of hepatocellular carcinoma tissue depends on its differentiation
      degree.
AB  - Quantitative characteristics of vessels in hepatocellular carcinoma and adjacent
      liver tissue were studied by morphometric methods after immunohistochemical
      staining for CD34 and CD105. The number of immunopositive vessels decreased with
      reduction of tumor histological differentiation degree.

PMID- 22977854
TI  - Changes in nitric oxide and superoxide levels in human endotheliocytes and
      carcinoma cells after exposure to low-dose ionizing radiation.
AB  - The exposure of HeLa G63 and ECV-304 cells to gamma-rays of (137)Cs as well as
      beta-particles of (3)H(2)O and (3)H-thymidine induced changes in redox status of
      not only irradiated cells, but also their progeny. Increased intracellular levels
      of nitric oxide (NO) were observed only in HeLa G63 cells and persisted over
      three cell generations; beta-particles from (3)H(2)O were most efficient.
      Intracellular superoxide (O(2)(-)) level had similar dynamics in both cell lines.
      Intracellular O(2)(-) level decreased immediately after irradiation, but then
      increased and significantly surpassed the control level. These changes in the
      intracellular level of O(2)(-) were accompanied by decondensation of nuclear
      chromatin. Increased level of free radicals in the progeny of irradiated cells
      and changes in chromatin conformation and the absence of correlation between
      radiation-induced structural damage to chromosomes and intracellular level of
      free radicals suggest participation of epigenetic mechanisms of inheritance.

PMID- 22977855
TI  - Proteasome activity and their subunit composition in endometrial cancer tissue:
      correlations with clinical morphological parameters.
AB  - The development of endometrial cancer is related to the status of the
      intracellular proteasome system. Total proteasome activity and pools 26S and 20S
      activities are higher in tumor tissue than in intact endometrium, and their
      composition is different. The expression of alpha1alpha2alpha3alpha5alpha6alpha7
      is lower in endometrial cancer tissue in comparison with intact endometrium and
      the content of immune subunits LMP7, LMP2, and PA28beta is increased. Total
      proteasome activity depends on the disease stage.

PMID- 22977856
TI  - Activities of clotting, fibrinolytic, and anticoagulant components of plasma
      hemostasis in patients with degenerative diseases of large joints.
AB  - Analysis of plasma hemostasis parameters was carried out in 110 patients with
      degenerative diseases of hip or knee joints hospitalized for initial
      endoprosthetics. Molecular markers of clotting and fibrinolysis and physiological
      anticoagulants were studied. Activities of all components of plasma hemostasis
      were normal in 29.4% patients. In 54.1% patients, high clotting activity was
      compensated for by adequate fibrinolysis activity. High thrombin formation was
      compensated for by high consumption of physiological anticoagulants in 10.1%
      patients. In 6.4% patients, high clotting activity was not paralleled by high
      fibrinolytic activity.

PMID- 22977857
TI  - Oxygen-binding characteristics of erythrocyte in children with type I diabetes
      mellitus of different duration.
AB  - Oxygen-binding properties of erythrocyte hemoglobin were studied in children with
      type 1 diabetes mellitus by Raman spectroscopy. The content of hemoglobin-oxygen
      complexes increased significantly only in children with lasting disease (more
      than 1 year); oxygen-binding capacity of hemoglobin is significantly changed,
      while its capacity to release oxygen remained unchanged. These changes were
      paralleled by alteration of hemoglobin affinity for oxygen. The area and content
      of hemoglobin were studied by laser interference microscopy. Hemoglobin content
      increased significantly in erythrocytes of patients with a more than 1-year
      history of type 1 diabetes mellitus. In these children, a significant inverse
      correlation between oxyhemoglobin fraction, oxygen binding capacity, and
      cholesterol content was found, this clinical parameter positively correlated with
      affinity for oxygen measured by Raman spectroscopy.

PMID- 22977858
TI  - Protamine and fertilin mRNA: potential biomarkers of assisted reproductive
      technology outcomes.
AB  - We studied the relationship between the levels of protamines 1 and 2 (PRM1 and
      PRM2) and fertilin-beta (ADAM-2) mRNA expression and outcomes of infertility
      treatment using assisted reproductive technologies was studied. Analysis of the
      relationships between the outcomes of in vitro fertilization and embryo transfer
      and profiles of the expression of seminal genes PRM1, PRM2, ADAM-2 mRNA,
      evaluated by reverse transcription quantitative PCR was carried out in 79
      couples. Significant differences in the expression of seminal PRM1, PRM2, ADAM-2
      mRNA were detected in couples with different outcomes of in vitro fertilization
      and embryo transfer. The levels of seminal gene expression are potential
      predictors of the efficiency of in vitro fertilization and embryo transfer.

PMID- 22977859
TI  - Morphofunctional changes in the kidneys in chronic endotoxemia against the
      background of hypothyroidism.
AB  - We studied morphological structure of the kidneys in chronic endotoxemia modeled
      against the background of hypothyroidism. The detected changes did not differ
      from those under conditions of basic endotoxemia model and were characterized by
      the development of glomerulosclerosis and glomerulohyalinosis. The changes were
      less severe in rats with hypothyroidism and appeared at the late terms of the
      experiment. This indicated a moderate protective effect of preexisting thyroid
      hormone deficiency.

PMID- 22977860
TI  - Electron microscopy of rat liver after intravenous injection of nanosized
      magnetite suspension.
AB  - Rat liver was examined by transmission electron microscopy after a single
      intravenous injection of nanosized magnetite suspension (0.1 g (Fe(3)O(4))/kg
      body weight). Magnetite particles were found in Kupffer's cells and hepatocytes.
      Accumulation of the particles by these two cell types was different. Morphometry
      of magnetite-containing granules in Kupffer's cells and nanoparticle
      agglomerations in hepatocytes was carried out. The ultrastructure of Kupffer's
      cell granules was described and the mechanism of penetration of nanosized
      magnetite particles into the cells was suggested. Nanosized magnetite particles
      were not completely eliminated over 40 days after a single injection.

PMID- 22977862
TI  - Apoptosis as a mechanism of maxillary sinus mucosa injury in rats after
      experimental transection of the maxillary nerve.
AB  - Transection of the maxillary nerve initiates apoptosis of the maxillary sinus
      mucosa cells in rats. Significant activation of apoptosis and proapoptotic factor
      p53 was found in the epithelium during week 1 after nerve transection. In delayed
      period after injury, apoptotic cells predominated in the submucosa against the
      background of Bcl-2 hypoexpression.

PMID- 22977861
TI  - Experimental study of the effects of highly intense laser exposure on hepatic
      tissue.
AB  - Irreversible changes in the liver tissue after high-intensity laser exposure
      develop at a depth of no more than 200 MU. Inflammatory reaction in the wounds
      does not depend on laser source and is characterized by predominance of
      proliferative processes leading by day 15 after surgery to the formation of a
      fine cicatrix. Hermetic sealing of the parenchymatous hepatic wound by laser
      welding to xenogenous peritoneum is no less effective than TahoComb and Beriplast
      P drugs and deserves further studies and clinical use.

PMID- 22977863
TI  - Development of an experimental model of cardiac failure combined with type I
      diabetes mellitus.
AB  - The doses and mode of streptozotocin injection for modeling heart failure
      combined with type 1 diabetes mellitus have been determined. Combined disease was
      induced in animals by injecting the selected streptozotocin dose (60 mg/kg
      intraperitoneally) at the stage of heart failure formation (2 weeks after
      coronary occlusion). This protocol of experiment led to development of
      hyperglycemia, body weight loss, and formation of myocardial cicatrix and
      hypertrophy corresponding to signs of heart failure paralleled by diabetes
      mellitus.

PMID- 22977864
TI  - Effects of the standard and endoliquor injection of estradurin on the rat
      prostate.
AB  - The effects of intramuscular and endoliquor routes of administration of water
      soluble antiandrogenic drug estradurin on proliferative activity of the prostate
      were studied. Estradurin injection via both routes produced a suppressive effect
      on the prostate. The effect of the minimum estradurin dose injected into the
      liquor was most manifest and not paralleled by side effects.

PMID- 22977865
TI  - Resident stem cells in the myocardium of patients with obstructive hypertrophic
      cardiomyopathy.
AB  - Interventricular septum myocardium was studied in 40 patients with obstructive
      hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive
      resident cardiac stem cells in 82.5% patients. The content of the connective
      tissue and myofibrillar disarray zones and the degree of cardiomyocyte
      hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing
      atrial natriuretic peptide were detected in the interventricular septum
      myocardium. The data were compared with clinical and functional parameters of
      patients. It was found that cardiac stem cells are present in patients, whose
      myocardium was characterized by increased density of the connective tissue,
      hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and
      accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

PMID- 22977866
TI  - Expression of carbohydrate metabolism markers in full-term spontaneous and
      induced pregnancy.
AB  - Peculiarities of the expression of glucose transporter (GLUT1 and GLUT3) and
      insulin-like growth factor immunophenotypes in placental villi in full-term
      physiological pregnancy were studied by immunohistochemical method. In induced
      pregnancy, changes of different degree in the expression of carbohydrate
      metabolism markers were detected (most pronounced changes were detected in GLUT3
      expression), which was probably associated with higher incidence of obstetrician
      complications in these patients.

PMID- 22977867
TI  - Improvement of cardiac contractile function in rats with postinfarction
      cardiosclerosis after transplantation of mononuclear and multipotent stroma bone
      marrow cells.
AB  - We compared the efficiency of autologous mononuclear cells and multipotent
      stromal cells of the bone marrow after their non-selective intracoronary
      transplantation on day 30 after acute coronary infarction in rats. Improvement of
      hemodynamic parameters of myocardial contractility (rates of left ventricular
      pressure rise and drop) in comparison with the initial values and deceleration of
      postinfarction prolongation of QRS and QT intervals were observed in rats of the
      experimental group in contrast to controls in 4 weeks after transplantation.
      These functional changes were more intensive after transplantation of multipotent
      stromal cells and were accompanied by more pronounced morphological signs of
      reverse myocardial remodeling: thickening of the scarred left ventricular wall,
      shrinkage of the scar, and decrease in left ventricular dilatation index.

PMID- 22977868
TI  - Burn-healing effects of a composition containing chitosan gel and a blood serum
      bioregulator.
AB  - We studied the effect of combined preparation on the basis of chitosan containing
      a bioregulator isolated from cattle serum in a concentration of 10(-10) mg/ml on
      healing of II-IIIa degree skin burns in mammals in vivo.

PMID- 22977869
TI  - Effect of recombinant erythropoietin on functional activity of cultured human
      cells.
AB  - We studied the effect of recombinant human erythropoietin on functional activity
      of skin cells in vitro. It was found that erythropoietin stimulated proliferation
      of mesenchymal and epithelial cells and effectively protected epidermal HaCaT
      cells from apoptosis. Insignificant effect of erythropoietin on contraction of
      collagen gel by mesenchymal cells was revealed. These findings suggest that
      erythropoietin can be a promising component of wound-healing preparations.

PMID- 22977870
TI  - Tetrapeptide H-Ala-Glu-Asp-Arg-OH stimulates expression of cytoskeletal and
      nuclear matrix proteins.
AB  - Tetrapeptide H-Ala-Glu-Asp-Arg-OH enhances the expression of cytoskeletal (actin,
      tubulin, vimentin) and nuclear matrix proteins (lamin A, lamin C) in cultured
      mouse embryonic fibroblasts by 2-5 and 2-3 times, respectively. Thus, the
      previously reported cardioprotective activity of this tetrapeptide is determined
      by its capacity to activate synthesis of cytoskeletal and nuclear matrix
      proteins, which stimulates cell proliferation and reduces apoptosis.

PMID- 22977871
TI  - Protective effect of transplantation of neonatal liver cell nuclei on the model
      of acute toxic hepatitis.
AB  - We present the results of comparative analysis of functional and morphological
      changes in the liver of animals with experimental CCl(4)-induced hepatitis under
      conditions of transplantation of neonatal liver cells and nuclei. It was found
      that transplantation of neonatal liver cell nuclei in acute toxic hepatitis
      provides better functional and structural state of the target organ.

PMID- 22977872
TI  - Effect of tripeptide Lys-Glu-Asp on physiological activity of
      neuroimmunoendocrine system cells.
AB  - Tripeptide Lys-Glu-Asp stimulates proliferation and inhibits apoptosis in
      organotypic cultures of neuroimmunoendocrine system cells. Lys-Glu-Asp
      accelerates cell renewal processes (decrease of apoptosis marker p53 and increase
      of proliferation marker Ki-67) in the pineal gland; this effect is more
      pronounced in cultures derived from old animals than in young cultures. The
      tripeptide induces the expression of low-differentiated lymphocyte marker CD5 and
      macrophage marker CD68, but in "old" cultures this effect is less pronounced than
      in "young" ones. Thus, in tissue culture Lys-Glu-Asp primarily affects the
      nervous and endocrine tissues during aging and produces a less pronounced effect
      on the nervous tissue. Physiological activity of the tripeptide consists in
      modulation of associative learning of honey bee in the model of short-term and
      the long-term memory.

PMID- 22977873
TI  - Effect of amino acids on expression of signal molecules in organotypic culture of
      the spleen.
AB  - Opposite effects of amino acids on proliferation and differentiation of immune
      cells in organotypic culture of the spleen were demonstrated. It was found that
      methionine stimulates differentiation of CD5(+) lymphocyte precursors into T
      helpers, cytotoxic T lymphocytes, and B cells and induces proliferation of
      CD68(+)-macrophages. Glutamic acid and arginine induce proliferation of B cells,
      while histidine and leucine promote differentiation of precursors towards
      cytotoxic T cells. The opposite effects of amino acids on immune cells of the
      spleen are related to different hydrophobicity of their side chains determining
      the type of intermolecular interaction.

PMID- 22977874
TI  - Mechanism of targeted migration of mesenchymal stem cells.
AB  - Experiments performed on mice C57Bl/6 with the use of GFP technology showed that
      activation of apoptosis is a potent physiological stimulus for targeted migration
      of mesenchymal stem cell from the blood to tissues. The effect of apoptosis
      induced targeted migration of stem cells can be used in cell therapy of damaged
      organs and tissues in various pathological states.

PMID- 22977875
TI  - Banks of cell cultures for biotechnology.
AB  - Seeding and working cell banks were created and stored in cell culture
      collection. The banks were certified in accordance with international and
      national requirements. Cultures of 293, MT-4, L-68, FECH-16-1, FECH-16-2, 4647,
      MDCK, CHO TK(-), and CHO pE cells were recommended by Medical Immunobiological
      Preparation Committee for the use in the production of medical immunobiological
      preparations. The stock is sufficient enough for supplying standard cell material
      for the production of medical immunobiological preparations over few decades.

PMID- 22977876
TI  - Neuroprotective effect of mesenchymal and neural stem and progenitor cells on
      sensorimotor recovery after brain injury.
AB  - We studied the effect of systemic administration of multipotent stem cells on
      impaired neurological status in rats with brain injury. It was found that
      transplantation of multipotent mesenchymal stromal cells of the bone marrow or
      human neural stem and progenitor cells to rats with local brain injury promoted
      recovery of the brain control over locomotor function and proprioceptive
      sensitivity of forelegs. The dynamics of neurological recovery was similar after
      transplantation of fetal neural stem and progenitor cells and multipotent
      mesenchymal stromal cells. Transplantation of cell cultures improved survival of
      experimental animals. It should be noted that administration of neural stem and
      progenitor cells prevented animal death not only in the acute traumatic period,
      but also in delayed periods.

PMID- 22977877
TI  - Simultaneous determination of nabumetone and its principal metabolite in
      medicines and human urine by time-resolved fluorescence.
AB  - A simple fluorescent methodology for the simultaneous determination of nabumetone
      and its main metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), in
      pharmaceutical preparations and human urine is proposed. Due to the strong
      overlapping between the fluorescence spectra of both analytes, the use of
      fluorescence decay curves to resolve their mixture is proposed, since these
      curves are more selective. Values of dependent instrumental variables affecting
      the signal-to-noise ratio were fixed using a simplex optimization procedure. A
      factorial design with three levels per factor coupled to a central composite
      design was selected to obtain a calibration matrix of thirteen standards plus one
      blank sample that was processed using a partial least-squares (PLS) analysis. In
      order to assess the goodness of the proposed method, a prediction set of ten
      synthetic samples was analyzed, obtaining recovery percentages between 97 and
      105%. Limits of detection, calculated by means of a new criterion, were 0.96 MUg
      L(-1) and 0.88 MUg L(-1) for nabumetone and 6-MNA, respectively. The method was
      also tested in the pharmaceutical preparation Relif, which contains nabumetone,
      obtaining recovery percentages close to 100%. Finally, the simultaneous
      determination of both analytes in human urine samples was successfully carried
      out by the PLS-analysis of a matrix of fifteen standards plus four analyte blanks
      and the use of the standard addition technique. Although urine shows native
      fluorescence, no extraction method or prior separation of the analytes was
      needed.

PMID- 22977878
TI  - Ionophore-based ion optodes without a reference ion: electrogenerated
      chemiluminescence for potentiometric sensors.
AB  - We report here on an electrogenerated chemiluminescence (ECL) readout for
      potentiometric ion-sensors, thereby offering an optical sensor output without the
      need for a reference ion (typically the hydrogen ion) that inconveniences
      ionophore based optical sensor principles. The compartment for ECL generation is
      physically separated from the sample by a bridge, and no current flows through
      the sample compartment. Here, three different types of ion selective membranes
      (Ca(2+), Na(+) and K(+)) are read-out individually and sequentially with this
      methodology. The repeatabilities are found as 0.5 to 1% of integrated light
      output, which translates into a relative uncertainty in the activity measurement
      of about 10%. This uncertainty appears to originate primarily at the ECL
      generating gold electrode, not at the potentiometric sensor. Other analytical
      figures of merit such as measuring range, sensitivity, optimal applied potential
      for ECL generation, and ion selectivity are also described.

PMID- 22977879
TI  - Recent developments and future possibilities for polymer monoliths in separation
      science.
AB  - Within recent years there has been an increase in research focused on the design
      and application of organic polymer monoliths in all areas of separation science.
      This is largely driven by the theoretical and practical benefits that these
      materials should be able to provide, particularly in terms of improved
      biocompatibility and high permeability. This review summarises recent new
      developments in this field with a focus on new approaches to the design and
      synthesis of polymeric monolithic materials for analytical separation science.
      This includes the use of alternative synthetic methodologies such as the
      development of hyper-crosslinked monoliths, preparation of hybrid materials and
      incorporation of nanostructures in the polymeric scaffold. New and developing
      approaches for the structural characterisation of monolithic columns are also
      included. Finally, we critically discuss the current chromatographic performances
      achieved with this column technology as well as where future developments in this
      field may be directed.

PMID- 22977880
TI  - Investigation of ion-ion-recombination at atmospheric pressure with a pulsed
      electron gun.
AB  - For future development of simple miniaturized sensors based on pulsed atmospheric
      pressure ionization as known from ion mobility spectrometry, we investigated the
      reaction kinetics of ion-ion-recombination to establish selective ion suppression
      as an easy to apply separation technique for otherwise non-selective ion
      detectors. Therefore, the recombination rates of different positive ion species,
      such as protonated water clusters H(+)(H(2)O)(n) (positive reactant ions),
      acetone, ammonia and dimethyl-methylphosphonate ions, all recombining with
      negative oxygen clusters O(2)(-)(H(2)O)(n) (negative reactant ions) in a field
      free reaction region, are measured and compared. For all experiments, we use a
      drift tube ion mobility spectrometer equipped with a non-radioactive electron gun
      for pulsed atmospheric pressure ionization of the analytes. Both, ionization and
      recombination times are controlled by the duty cycle and repetition rate of the
      electron emission from the electron gun. Thus, it is possible to investigate the
      ion loss caused by ion-ion-recombination depending on the recombination time
      defined as the time delay between the end of the electron emission and the ion
      injection into the drift tube. Furthermore, the effect of the initial total ion
      density in the reaction region on the ion-ion-recombination rate is investigated
      by varying the density of the emitted electrons.

PMID- 22977881
TI  - All polymer chip for amperometric studies of transmitter release from large
      groups of neuronal cells.
AB  - We present an all polymer electrochemical chip for simple detection of
      transmitter release from large groups of cultured PC 12 cells. Conductive polymer
      PEDOT:tosylate microelectrodes were used together with constant potential
      amperometry to obtain easy-to-analyze oxidation signals from potassium-induced
      release of transmitter molecules. The nature of the resulting current peaks is
      discussed, and the time for restoring transmitter reservoirs is studied. The
      relationship between released transmitters and potassium concentration was found
      to fit to a sigmoidal dose-response curve. Finally, we demonstrate how the
      presented device can be used for simple drug screening purposes, by measuring the
      increase of transmitter release due to short-term treatment with L-DOPA.

PMID- 22977882
TI  - Combining atomic force-fluorescence microscopy with a stretching device for
      analyzing mechanotransduction processes in living cells.
AB  - Mechanical forces affect biological systems in their natural environment in a
      widespread manner. Mechanical stress may either stimulate cells or even induce
      pathological processes. Cells sensing mechanical stress usually respond to such
      stressors with proliferation or differentiation. Hence, for in vitro studies, the
      ability to impose a controlled mechanical stress on cells combined with
      appropriate analytical tools providing an immediate answer is essential to
      understand such fundamental processes. Here, we present a novel uniaxial
      motorized cell stretching device that has been integrated into a combined
      fluorescence microscope (FM)-atomic force microscope (AFM) system, thereby
      enabling high-resolution topographic and fluorescent live cell imaging. This
      unique tool allows the investigation of mechanotransduction processes, as the
      cells may be exposed to deliberately controlled mechanical stress while
      simultaneously facilitating fluorescence imaging and AFM studies. The developed
      stretching device allows applying reproducible uniaxial strain from
      physiologically relevant to hyperphysiological levels to cultured cells grown on
      elastic polydimethylsiloxane (PDMS) membranes. Exemplarily, stretching
      experiments are shown for transfected squamous cell carcinoma cells (SCC-25)
      expressing fluorescent labeled cytokeratin, whereby fluorescence imaging and
      simultaneously performed AFM measurements reveal the cytokeratin (CSK) network.
      Topographical changes and mechanical characteristics such as elasticity changes
      were determined via AFM while the cells were exposed to mechanical stress. By
      applying a cell deformation of approx. 20%, changes in the Young's modulus of the
      cytoskeletal network due to stretching of the cells were observed. Consequently,
      integrating a stretching device into the combined atomic force-fluorescence
      microscope provides a unique tool for dynamically analyzing structural remodeling
      and mechanical properties in mechanically stressed cells.

PMID- 22977883
TI  - Gold nanorods as surface enhanced Raman spectroscopy substrates for sensitive and
      selective detection of ultra-low levels of dithiocarbamate pesticides.
AB  - We report the use of gold nanorods as solution-based SERS substrates for the
      detection of ultralow-levels of three different dithiocarbamate fungicides:
      thiram, ferbam and ziram. Gold nanorods are attractive to use as SERS substrates
      due to the ability to tune the surface plasmon resonance of the nanoparticles to
      the laser excitation wavelength of the Raman spectrometer equipped with a 785 nm
      diode laser. The gold nanorods are synthesized using a seed-mediated growth
      method and characterized using UV-Visible spectroscopy, zeta potential, and TEM.
      The gold nanorods have an aspect ratio of 2.19 +/- 0.21 and have an average
      length of 37.81 +/- 4.83 nm. SERS spectra are acquired at different
      concentrations of each fungicide and calibration curves are obtained by
      monitoring the intensity of the band arising from the nu(C-N) stretching mode
      coupled to the symmetric delta(CH(3)) motion. The limits of detection and limits
      of quantitation are obtained for each fungicide. The limits of detection are
      11.00 +/- 0.95 nM, 8.00 +/- 1.01 nM, and 4.20 +/- 1.22 nM for thiram, ferbam, and
      ziram respectively. The limits of quantitation are 34.43 +/- 0.95 nM, 25.61 +/-
      1.01 nM, and 12.94 +/- 1.22 nM for thiram, ferbam, and ziram respectively. It can
      be seen that the three different dithiocarbamates can be detected in the low nM
      range based on the limits of detection that are achieved.

PMID- 22977884
TI  - Design, synthesis and evaluation of small molecule reactive oxygen species
      generators as selective Mycobacterium tuberculosis inhibitors.
AB  - Here, we report 5-hydroxy-1,2,3,4,4a,9a-hexahydro-1,4-ethano-9,10-anthraquinone
      (13), a small molecule generating reactive oxygen species (ROS) in pH 7.4 buffer
      under ambient aerobic conditions that has selective and potent Mycobacterium
      tuberculosis growth inhibitory activity.

PMID- 22977885
TI  - Many M(c)B(n) boron wheels are local, but not global minima.
AB  - Twenty-six planar boron wheels with a central hypercoordinate atom (M(c)B(n), M
      is a 2nd or 3rd period element) were designed following the Schleyer-Boldyrev
      concept of geometric and electronic fit whereby in-plane sigma- as well as pi
      aromaticity contribute to the chemical bonding. Global minimum searches using an
      efficient newly implemented method reveal that most of these boron wheels are
      only local, rather than global minima. However, the Be(c)B(8) triplet planar
      wheel global minimum is a new member of the planar hypercoordinate M(c)B(n)
      family. Six categories classify the structures of the other global minima: planar
      wheels, planar non-wheel forms, quasi-two-center-wheels, as well as leaf-like,
      pyramid-like, and umbrella-like geometries.

PMID- 22977886
TI  - Theoretical study of the gauche-trans equilibrium with and without an
      intramolecular hydrogen bond for +H3NCH2CH2X systems (X = OH, NH2, COO-) in
      solution.
AB  - The gauche-trans conformational equilibrium has been studied for
      (+)H(3)NCH(2)CH(2)X systems (X = OH, NH(2), COO(-)) and for the neutral model of
      the simplest beta-amino acid in aqueous solution and chloroform. Each structure
      exhibits an intramolecular hydrogen bond in the NCCX gauche conformation, which
      is necessarily disrupted in the local energy minimum trans form. Geometries were
      optimized at the IEF-PCM/B97D/aug-cc-pvtz level of theory and indicated that the
      solvent effect of chloroform vs. water is moderate when the geometries for the
      corresponding gauche and trans conformers are compared. The only remarkable
      difference was found for beta-alanine, which can exist in gauche, zwitterionic
      form in aqueous solution but not in chloroform. Total relative free energies were
      obtained as the sum of the relative IEF-PCM/B97D/aug-cc-pvtz internal free energy
      and DeltaG(solv). The latter was calculated both by means of IEF-PCM and the
      explicit solvent FEP/Monte Carlo methods. The resulting DeltaG(tot) values could
      differ by 1-2 kcal mol(-1) depending on the accepted DeltaG(solv) value, but any
      calculation indicated that the internally bound gauche conformers are far more
      populated than the corresponding trans species. A difference of 2.6 kcal mol(-1)
      for DeltaG(solv) by the two methods resulted in the preference of the
      zwitterionic gauche beta-alanine structure by FEP/MC in contrast to IEF-PCM
      favoring the neutral form in aqueous solution. Monte Carlo characterization of
      the solution structure in the first solvation shell of polar groups indicates
      that solvation of a N-H(+) bond is sensitive to its involvement in an
      intramolecular hydrogen bond. For the zwitterionic, gauche beta-alanine, almost
      no water oxygen can reach that N-H(+) bond, which is in strong interaction with
      the -COO(-) group by forming a six-membered ring and favorable local geometry for
      the hydrogen bond.

PMID- 22977887
TI  - Hybrid materials based on lanthanide organic complexes: a review.
AB  - A great deal of research has been carried out on lanthanide organic complex-based
      organic-inorganic hybrid materials in the last decade. This critical review
      begins with a formulation of the fundamentals of lanthanide organic complex
      luminescence, and presents various current designed ideas, synthetic routes,
      luminescence behaviors and potentials of the latest advanced (a) sol-gel
      materials, (b) mesoporous materials, (c) titania materials, (d) ionic liquids and
      ionogels, (e) polymers, and (f) bifunctional magnetic-optical composites based on
      lanthanide organic complexes. Finally, challenges and opportunities for further
      improvement of organic-inorganic hybrid luminescent materials based on lanthanide
      organic complexes will be discussed.

PMID- 22977888
TI  - [Knowledge, attitude, and practice of traditional healers on the topic of malaria
      in the city of Abidjan].
AB  - INTRODUCTION: An estimated 300 to 500 million clinical cases of malaria occur
      each year worldwide, 90% in Africa, mostly among young children. In Cote
      d'Ivoire, malaria is 46.03% of disease states and 62.44% of hospital admissions.
      In children under 5 years, it is 42.67% of the reasons for consultation and
      59.68% of hospital admissions. In pregnant women, it represents 22.91% of disease
      states and 36.07% of hospital admissions. In Africa, traditional medicine is the
      first resort for the vast majority of people, because of its accessibility both
      geographically, economically and culturally. However, some modern practitioners
      show an attitude of distrust of traditional medicine and its players, calling
      them irrational. This work had set out to assess knowledge, attitudes and
      practices of traditional healers in the uncomplicated and complicated in the
      context of collaboration between traditional and modern medicine for the optimal
      management of critical cases. MATERIALS AND METHOD: The study focused on
      traditional healers practicing in the city of Abidjan. The study was conducted
      using individual interviews over a period of 30 days. The interviews were
      conducted in local languages, with the assistance, if necessary, translators. For
      data collection, we used a questionnaire containing four items: the socio
      demographic characteristics of traditional healers, their knowledge on malaria,
      diagnostic practices and traditional therapies. RESULTS: Of the 60 healers and
      included in the study, only six were women (10%), a sex-ratio of a woman to 9
      men. 66.7% of respondents traditional healers are herbalists and 25% of
      naturopaths.Only 8.3% were spiritualists. The etiology of malaria most commonly
      cited by the traditional healers were mosquito bites (16.7%), food (1.7%), solar
      (1.7%) and fatigue (1.7%) . 25% of traditional healers are associated with
      mosquitoes, sun and fatigue. Symptomatology most cited were fever (100%), dark
      urine (86%), the yellow or pale conjunctiva (80%), vomiting (71.7%), nausea
      (58.3%) and abdominal pain (48.3%). Traditional healers recognized three types of
      malaria: the white shape, form yellow / red and the black form. Traditional
      healers malarious patients surveyed were receiving both first (58.3%) than second
      line (41.7%). 78.3% of them practiced an interview and physical examination of
      theirpatients before the diagnosis. In 13.3% of cases they were divinatory
      consultation. Medications used to treat malaria were herbal in 95% of cases. The
      main sign of healing was the lack of fever (58.3%). 90%of traditional healers
      interviewed referring cases of malaria black (severe malaria). This reference is
      made to modern health facilities (90.2%). 68.3% of respondents practiced
      traditional healers of malaria prophylaxis among pregnant women and children
      under 5 years. CONCLUSION: A description of clinical malaria by traditional
      practitioners in health is not very far from that of modern medicine.
      Nevertheless, the logics of our respondents are etiological more complex and
      linked to their cultural context. The management of cases is made from medicinal
      plants in treatment failure patients are usually referred to modern health
      facilities. The involvement of traditional healers in the detection and quick
      reference risk cases can contribute to reducing child mortality due to severe
      malaria.

PMID- 22977889
TI  - [Prevalence of respiratory disorders in women exposed to the smoke from smoking
      fish in the municipality of Cotonou, Benin].
AB  - INTRODUCTION: Women are constantly exposed to fumes and gases produced by burning
      wood, however they are poorly studied. The aim of this study was to assess the
      prevalence of respiratory disorders among women most at risk. SUBJECTS AND
      METHODS: We conducted a descriptive, transversal and prospective women engaged
      with the site of artisanal smoked fish Hwlacodji in Cotonou. The survey included
      a questionnaire exploring the medical history and pathological respiratory events
      occurred during the last 12 months. All had received spirometry testing. RESULTS:
      84 women were included. The average age was 37 +/- 12 years, with extremes of 18
      and 70 years. More than half of respondents had a tenure of more than 20 years
      and 61/84 (73%) practiced this profession full time. 70 (83%) had at least one
      respiratory symptom. The reported symptoms were: rhinitis 77%, 70% cough, dyspnea
      65% and 19% have gone out of business last year due to lung disease. Ventilatory
      abnormalities are found in 49% of respondents. Abnormalities relate to FEV / FVC
      <0.8: 3 (3.5%), PEF <0, 8: 10 (11.90%), FEV <0.8: 10 (11.90%). CONCLUSION: The
      respiratory symptoms is quite expressive contrasts with spirometric results.
      Monitoring over a long period of mostly young women will help lead to meaningful
      conclusions.

PMID- 22977890
TI  - [Problems with the management of myocardial infarction at the Desegou Hospital].
AB  - INTRODUCTION: Myocardial infarction is a major emergency involving life
      threatening in the absence of appropriate treatment. The aim of this study was to
      analyze the problem of management of myocardial infarction in a second reference
      hospital in Mali. PATIENTS AND METHODS: This was a prospective descriptive study
      over a period of six months from January to June 2010. It concerned all patients
      admitted for myocardial infarction in intensive care.The diagnosis was suspected
      in chest pain or the occurrence of complications (PAO, cardiogenic shock) and
      electrocardiogram signs on at least two precordial leads. The parameters studied
      were: age,reason for admission, risk factors, hemodynamic parameters, the
      deadline for completion of the ECG, the topography of lesions and electrical
      changes within 15 days. RESULTS: A male was found with a mean age of 54.62 years.
      Chest pain was the main reason for admission (6 cases) followed by cardiogenic
      shock (1 case) and acute pulmonary edema (1 case). The electrocardiogram was
      performed in 7 patients more than 24 hours after admission. The anterior
      territory was the most affected. On admission three patients had a systolic
      pressure below 90 mmHg.The evolution was marked by occurred heart failure (3
      cases) and death (2 cases). CONCLUSION: The lack of diagnostic and therapeutic
      method in our heath facility helps to increase morbidity and mortality associated
      with myocardial infarction.

PMID- 22977891
TI  - [Twin pregnancy after tubal ligation: case report].
AB  - The binding of the horns takes a place growing among the various processes of
      birth-control. This binding of the horns is almost irreversible and the women who
      make recourse to this method are generally saddles which think of having achieved
      their families.

PMID- 22977892
TI  - The independent drug information service, dresden, Germany in its 10th
      anniversary year.

PMID- 22977893
TI  - Expert panel on nursing theory guided practice position paper: nursing knowledge
      and the impact on Nursing's Preferred Future a plan for enhancing Raise the Voice
      Phase II.

PMID- 22977894
TI  - Hepatitis C screening and testing: a call for a national response.

PMID- 22977895
TI  - Protein-protein interactions. Preface.

PMID- 22977896
TI  - Is antiepileptogenesis a realistic goal in clinical trials? Concerns and new
      horizons.
AB  - Any attempt to make antiepileptogenesis a realistic goal in clinical trials
      should be based on the experience of failures of the past. A wide variety of
      experimental studies and clinical trials using chronic antiseizure drug therapy
      during the extended post-injury period have had minimal success. The
      disappointing results of these studies may be due to several factors including
      the possibility that antiseizure drugs, despite the fact they suppress seizure
      activity, do not interfere in any substantial way with the "epileptogenic"
      process of focal epilepsies. Although the reasons for the failure are not
      entirely clear, it may be that the antiseizure drugs may have been tested at the
      wrong doses, for the wrong duration, or at the wrong time after brain injury.
      Surprisingly, the anti-absence drug ethosuximide has also been shown to be
      antiepileptogenic in several experimental models of absence epilepsy. In
      addition, clinical trials aimed at preventing focal post-injury epilepsy have
      suffered from poor enrolment and other issues related to the comorbidity of
      severe epilepsies that follow overt brain injury. Testing specific anti
      inflammatory and immunological antiepileptogenic agents to prevent focal
      epilepsies, as well as prevention trials for genetic epilepsies, possibly with
      anti-absence drugs, may be a way to resolve the dilemma. Although more evidence
      is needed, there is hope on the horizon for antiepileptogenic therapy that works.

PMID- 22977897
TI  - Antiepileptic drug trials: the view from the clinic.
AB  - A golden age of antiepileptic drug development has yielded over a dozen useful
      new compounds, but the nature of clinical trials has made translation to
      practical use in the clinic difficult. Most clinical trials are designed for
      regulatory purposes and fail to answer critical clinical questions. These
      questions include: which drug is best as initial therapy, which drugs work as
      monotherapy, what are good drug combinations, what is the best starting dose and
      titration schedule, what is a reasonable target dose, what is the shape of the
      dose-response curve and does it vary significantly between patients, what is the
      true incidence of side effects, and what is the long-term efficacy of the drug?
      Most of these questions could be answered by changing trial designs, but many
      changes would entail additional time and money. There are encouraging signs that
      trials with procedures more directly applicable to the clinic are becoming
      common. These include direct comparative trials, longer trials with emphasis on
      seizure freedom, and trials with more flexible dosing schedules. In the past,
      funding of longer and more naturalistic trials has fallen to government agencies,
      but commercial funding has been obtained for several recent studies. Better
      quality control, innovative endpoints, structured searching for side effects, and
      standardisation of data collection are also promising topics for development.

PMID- 22977898
TI  - What clinical trial designs have been used to test antiepileptic drugs and do we
      need to change them?
AB  - Designs used to evaluate the efficacy and safety of antiepileptic drugs (AEDs)
      have evolved considerably over the years. A major impulse to develop
      methodologically sound randomised controlled trials dates back to the Kefauver
      Harris Drug Amendment of 1962, through which the US congress introduced the
      requirement of substantial evidence for proof of efficacy in a new drug
      application. The mainstay for the initial approval of most new AEDs has been, and
      still is, the placebo-controlled adjunctive therapy trial, which evolved over the
      years from the cross-over to the parallel-group design. In the early days, when
      few AEDs were available, enrolment of patients into these trials was relatively
      easy and prolonged placebo exposure could be justified by lack of alternative
      treatment options. With more than 20 drugs now available to treat epilepsy,
      however, exposing patients to placebo or to a potentially ineffective
      investigational agent faces practical and ethical concerns. Recruitment
      difficulties have led sponsors to markedly increase the number of trial sites,
      but there is evidence that this may adversely affect the ability to differentiate
      between effective and ineffective treatments. Methodological and practical
      difficulties are also encountered with monotherapy trials. Because regulatory
      guidelines for monotherapy approval differ between Europe and the US, sponsors
      need to pursue separate and costly development programs on the two sides of the
      Atlantic. Moreover, the scientific validity of the monotherapy trial paradigms
      currently used in Europe (the non-inferiority design) and in the US (the
      conversion to monotherapy design with historical controls) has been questioned.
      This article will review these issues in some detail and discuss how trial
      designs and regulatory approval processes may evolve in the future to address
      these concerns.

PMID- 22977899
TI  - Novel trial designs for monotherapy.
AB  - Unlike many other areas of therapeutics, specific regulatory trial programmes are
      required to be undertaken in newly diagnosed epilepsy to support the licensing of
      novel antiepileptic drugs for use in drug-naive patients. To complicate matters
      further, American and European regulators have taken markedly different
      approaches to this issue, with the FDA requiring withdrawal to monotherapy data
      comparing more than one dose of newer agents with historical controls, whereas
      the EMA recommends undertaking randomised head-to-head studies versus an
      established comparator. The former studies are designed to show superiority
      compared to previously published data, whereas the latter will accept a non
      inferiority (equivalence) outcome. This paper discusses the positive and negative
      aspects of both designs and explores novel alternative options. Particular focus
      has been placed on placebo-controlled studies following a single seizure with
      supportive electroencephalographic and/or brain imaging evidence, in the hope of
      identifying a realistic design that will satisfy licensing authorities on both
      sides of the Atlantic Ocean.

PMID- 22977900
TI  - Clinical trials in acute repetitive seizures and status epilepticus.
AB  - This paper reviews the clinical trials in acute repetitive seizures and in tonic
      clonic status epilepticus. There are good randomised controlled studies on the
      use of benzodiazepines in early status epilepticus, but an inadequate trial base
      in the later stages. Therapy has therefore to be based on open studies, although
      in the later stages there is also a dearth of open data. Tonic-clonic status
      epilepticus is a medical emergency and a condition with a significant mortality.
      The lack of information compromises optimal therapy. This paper reviews the
      reasons for the lack of data and the problems associated with collecting data. It
      is proposed that, in the first instance, the best way of improving the quality of
      evidence would be a multinational case registry of existing practice.

PMID- 22977901
TI  - Who amongst us will be selected?

PMID- 22977902
TI  - Physician's lexicon: the florid eponyms of medicine.

PMID- 22977903
TI  - Policy and health.

PMID- 22977905
TI  - Proceedings of the 2nd Dalian International Symposium and Exhibition on
      Chromatography and Related Techniques, October 8-11, 2011, Dalian, China.

PMID- 22977904
TI  - National strategies and systems for occupational safety and health.

PMID- 22977906
TI  - Proceedings of a conference: Palliative Care of Cancer: an International
      Perspective, 2-4 April 2012, Ankara, Turkey.

PMID- 22977907
TI  - Special issue on the occasion of Otto Braun-Falco's 90th birthday.

PMID- 22977908
TI  - Special issue dedicated to Devi Subba Rao.

PMID- 22977909
TI  - Proceedings of the 10th International Symposium on Mass Spectrometry in the
      Health and Life Sciences: Molecular and Cellular Proteomics, August 2011, San
      Francisco, USA.

PMID- 22977910
TI  - Proceedings of the 55th International Meeting of Clinical Endocrinology, April 31
      May 06, 2012, Paris, France.

PMID- 22977911
TI  - Abstracts of the 10th European Congress of Neuropathology, June 6-9, 2012,
      Edinburgh, Scotland.

PMID- 22977912
TI  - Special issue in honor of Roger Gosden.

PMID- 22977913
TI  - Proceedings of the 12th International Conference on Biomedical Applications of
      Electrical Impedance Tomography, May 4-6, 2011, Bath, Great Britain.

PMID- 22977914
TI  - Dermacase: Can you identify this condition? Solitary mastocytoma.

PMID- 22977915
TI  - Heart Failure Congress 2012 promotes integration of pharmacology and technology.

PMID- 22977916
TI  - Novel pharmacotherapies for heart failure.

PMID- 22977917
TI  - Heart failure: a vision for the future.

PMID- 22977918
TI  - Commentary on physical activity and body mass perception.

PMID- 22977919
TI  - Chest X-ray quiz. Subcutaneous emphysema.

PMID- 22977920
TI  - The hidden hordes.
AB  - With funding for the HMP and Meta-HIT consortia now ending, what's next for these
      large-scale efforts to map the hidden microbial hordes associated with the human
      body?

PMID- 22977921
TI  - Abstracts of the 10th Congress of the European Association of NeuroOncology.
      Marseille, France. September 6-9, 2012.

PMID- 22977922
TI  - Respiratory issues.

PMID- 22977923
TI  - Expert consensus: renal denervation for the treatment of arterial hypertension.
AB  - Catheter-based renal denervation is a new method for disrupting renal sympathetic
      nerves in the adventitia of renal arteries. A randomized clinical trial showed a
      decrease in blood pressure (BP) in resistant hypertensive patients. To guide
      clinicians and interventional practitioners in the use of this new approach, the
      French Societies of Arterial Hypertension, Cardiology and Radiology decided to
      combine their expertise and propose a consensus document assessing the
      benefit/risk ratio of this technique in arterial hypertension. In 2012, this
      expert consensus proposed limiting renal denervation to patients with essential
      hypertension uncontrolled by four or more antihypertensive therapies and with:
      treatment that includes at least a diuretic; past or present exposure to
      spironolactone (at a dose >= 25 mg/d); and office BP greater or equal to 160 mmHg
      and/or 100 mmHg for systolic and diastolic BP, respectively, confirmed by daytime
      ambulatory or home BP measurement, with systolic BP greater than 135 mmHg and
      diastolic BP greater than 85 mmHg. Finally, renal artery anatomy and kidney
      function should allow proper intervention (i.e. two functional kidneys, absence
      of previous renal angioplasty). Renal denervation is a complex interventional
      procedure requiring appropriate training and associated with arterial
      complications. Antihypertensive treatment should not be interrupted immediately
      after renal denervation as the BP-lowering effect is delayed and reaches maximum
      effect after 3 months. Monitoring of BP, renal function and renal artery anatomy
      is required 12 months and 36 months after the procedure. The expert consensus
      requires the inclusion of patients experiencing this procedure in an
      observational study.

PMID- 22977924
TI  - Encouraging developments in maintaining heart and kidney health. One recent study
      finds a cholesterol-lowering drug is beneficial for patients with kidney disease,
      while another shows how kidney nerve ablation helps lower blood pressure.

PMID- 22977925
TI  - Understanding the realities of life with an ICD.  Expert advice about what
      activities should and shouldn't be avoided can help keep you safe and healthy.

PMID- 22977926
TI  - Lenient heart rate control may be as effective as strict control.  Patients with
      atrial fibrillation may experience similar outcomes and enjoy a similar quality
      of life with a less-rigid approach to rate control.

PMID- 22977927
TI  - Are sleeping pills safe if you have heart disease? Sufficient sleep is critical
      for heart health, but sleep aids require caution and a physician's advice.

PMID- 22977928
TI  - Research shows family stress linked to angina.  Reducing stress with physical
      exercise and other wellness behaviors can improve your emotional health and your
      heart health.

PMID- 22977929
TI  - Drug-eluting and bare-metal stents both safe in large arteries.  Patients with
      drug-eluting stents also have lower rates of revascularization.

PMID- 22977930
TI  - I live in a city where the air quality can be very poor at times.  Can you tell
      me how dangerous poor air quality can be for heart health, and how I can reduce
      the risk?

PMID- 22977931
TI  - I've had a pacemaker for many years and have developed persistent atrial
      fibrillation (AF). In the past three years, I've also had episodes of ventricular
      tachycardia (VT). I had valve surgery six years ago and am concerned that the
      pacemaker lead may have been damaged during surgery. What should I know about a
      replacement pacemaker?

PMID- 22977932
TI  - Choose the right omega-3 supplement for heart health.  Certain brands may be
      useless at best, dangerous at worst.  Here's what you need to know before you buy
      an omega-3 supplement.

PMID- 22977933
TI  - Dabigatran (Pradaxa). An alternative to warfarin (Coumadin) is approved to help
      treat patients with atrial fibrillation.

PMID- 22977934
TI  - Hysterectomy: a new risk factor for cardiovascular disease.  Study shows that the
      age at which a woman has the surgery may affect her heart disease risk, though
      the research shows varied results.

PMID- 22977935
TI  - Your mental health matters when it comes to your heart.  Study spells out the
      risks of depression and diabetes.

PMID- 22977936
TI  - After having bypass surgery, I got involved in heart-healthy cooking and have
      lost 12 pounds. Before surgery, I used to have a glass of wine with dinner, but I
      have not had one since. What's your opinion about an occasional drink?

PMID- 22977937
TI  - My mother was put on the betablocker metoprolol (Toprol) for high blood pressure.
      Now she thinks her diabetes is out of control because of it.  Can this be
      possible?

PMID- 22977938
TI  - I had a heart attack, and my husband had a stroke.  Our granddaughter will be 25
      this year.  We think she should be tested for heart disease, but our daughter
      feels she is too young.  Who is right?

PMID- 22977939
TI  - I am taking warfarin (Coumadin) for atrial fibrillation, but I don't know why.

PMID- 22977940
TI  - What's your opinion about eggs for people with heart disease?

PMID- 22977941
TI  - Reduce sodium intake and help manage your blood pressure.  The American Heart
      Association recommends limiting daily sodium consumption to 1,500 mg or less in a
      new call for action for 2011.

PMID- 22977942
TI  - Be prepared for AFib recurrence even after ablation treatment.  Research shows
      that symptoms may return within a few years, but the duration and frequency of
      episodes are usually improved after treatment.

PMID- 22977943
TI  - I recently had complicated retina surgery and was taken off warfarin for five
      days prior to the operation.  After the surgery, I was back on warfarin that
      evening.  A few days later a blood clot reached the right side of my brain and I
      have been left with some numbness and coldness on my left side.  Is there is a
      more conservative alternative to completely coming off warfarin?

PMID- 22977944
TI  - My doctor advised me to go on a low-sodium diet, hoping it would help bring down
      my blood pressure (BP). But after six months, there was no change. Is it possible
      that some people's BP is affected by salt/sodium and others are not?

PMID- 22977945
TI  - [Thorax/lung and mediastinum, pleura cancer].

PMID- 22977946
TI  - Findings of research misconduct.

PMID- 22977947
TI  - Measles in the Horn of Africa, 2010-2011.

PMID- 22977948
TI  - Outbreak news. Cholera, Sierra Leone.

PMID- 22977949
TI  - Outbreak news. Ebola haemorrhagic fever, Democratic Republic of the Congo.

PMID- 22977950
TI  - Outbreak news. Ebola haemorrhagic fever, Uganda.

PMID- 22977952
TI  - Outbreak news. Hantavirus pulmonary syndrome, Yosemite National Park, United
      States of America.

PMID- 22977951
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 2012.

PMID- 22977953
TI  - Global programme to eliminate lymphatic filariasis: progress report, 2011.

PMID- 22977954
TI  - [The biolaw and bioethics encyclopedia].
AB  - On 4 April 2011, as part of the XVIII Conference in Law and the Human Genome, the
      official presentation took place of the first Spanish language Encyclopedia of
      Biolaw and Bioethics, in an event organised by the Inter-University Chair in Law
      and the Human Genome held, on this occasion, in the new Auditorium of the
      University of the Basque Country. The Encyclopedia of Biolaw and Bioethics is a
      project which was conceived and driven forward by the Inter-University Chair in
      Law and the Human Genome. It was an ambitious project which was supported by the
      Roche Institute Foundation. It was therefore a magnum opus which began more than
      three years ago and which has required the work of more than 200 professionals
      from various disciplines in Spain, Latin America and Portugal. The encyclopaedia
      tries to make up for the lack of a suitable publication in the Spanish language
      that could be used as a reference and be consulted by different experts who have
      to tackle controversies and doubts posed in the field of biolaw and bioethics as
      part of their everyday work. The work makes it possible to ascertain the
      situation in this field regarding the most controversial issues and emerging
      conflicts, find out which values, assets or rights are involved or confronted,
      what solutions have been proposed by bioethics and the social positions that have
      been established through legal regulations. All in all, the encyclopaedia was the
      culmination of an ambitious undertaking, a pioneering work in the Spanish
      speaking countries due to its characteristics and scope. It is essential to have
      such a resource in today's cultural environment. The presentation of the
      Encyclopedia of Biolaw and Bioethics given by Mr. Del Barrio Seoane as Director
      General of the Roche Institute Foundation during the Conference deservers a
      special mention. The project has been consolidated through the support of this
      institution.

PMID- 22977955
TI  - The intersection between bioethics and human rights in the light of the universal
      declaration on bioethics and human rights.
AB  - This article aims to explore the increasing interconnection between bioethics and
      human rights that can be observed in recent international norms relating to
      biomedicine. To this end, the analysis has been focused on the Universal
      Declaration on Bioethics and Human Rights (UDBHR) adopted by UNESCO in 2005.
      Investigating the meanings of the intersection perceived in the UDBHR has led to
      the understanding of how bioethics and human rights are in accordance, under the
      normative perspective. Hence, in normative terms, the intersection between
      bioethics and human rights is clearly undisputable. However, there is no way to
      affirm that it is consolidated, as UDBHR's adoption is recent and its
      consolidation, together with its precepts, depends on state and non-state agents.
      The efficacy of a norm and its content depends on social, cultural and economic
      conditions, that is, it depends on a series of factors that influence the
      normative system. In the case of the UDBHR, its effective application and
      assimilation of its principles are directly linked to the use that bioethical
      institutions make of them and to how the community of bioethicists will project
      them in their thoughts and theory production. If, on the one hand UDBHR
      symbolizes the intersection confirmation--which is of extreme importance for its
      consolidation--on the other hand its range and consequent stabilization are
      submitted to the actions from governments, social institutions and bioethicists.
      Hence, there is still a lot to do in terms of introducing the human rights
      precepts into bioethics. The aim of this paper is to contribute to this goal.
      Thus based on the meanings of the intersection between bioethics and human rights
      identified in the UDBHR, this article presents five ways to understand the
      connection between these two fields.

PMID- 22977956
TI  - [Consent in DNA sample harvesting. With special reference to processes with
      minors (Part I)].
AB  - At present, there is no doubt as to the enormous importance of genetic testing
      for DNA markers in investigating crimes and identifying the guilty parties. We
      consider it unnecessary to sing the virtues of this celebrated method, which is
      now generally permitted by our courts, and which is forcing us to resolve diverse
      matters that the scarcity and insufficiency of current legislation is unable to
      settle. The objective of this paper is to analyse the consent given by the
      affected party to having genetic samples taken, as well as the inclusion of their
      profiles into police databases afterwards. This consent appears to be the main
      source of legitimacy in these scenarios. However, in order for it to take full
      effect, certain requirements must be met, especially in relation to the affected
      party giving informed consent. This means that in order for the consent to be
      considered valid, the victim must be informed of the legal scope and consequences
      that may arise from the test, as well as the legal consequences that may arise
      from their refusal. In the case of children, debate is needed as to whether they
      can be asked to give a genetic sample, if court authorisation or permission from
      their legal representatives or even their lawyer is always necessary or whether
      the informed, voluntary consent of the child might be sufficient, also whether
      police databases can or should have access to these samples.

PMID- 22977957
TI  - [Culpability and the problem of the human genome. Between being and having to
      be].
AB  - In a liberal-democratic system, there is no possibility of a criminal liability
      charge without a minimum of freedom. Nevertheless, since a long time ago and,
      nowadays, with the advancement of science in the human genome, understanding it
      as a closed system--farm theory--is intended to demonstrate that the genome is a
      destination, thus criminal liability will be void, giving rise to security
      measures.

PMID- 22977958
TI  - The legal status of human biological materials and the consequences in
      biobanking.
AB  - This paper discusses the legal status of human tissue when detached from the
      body. Scientific advances compel a change in legal perspective from the
      traditional 'material' view to recognise the 'informational' capacity of tissue.
      The aim of this article is to critically review this legal shift and its
      consequences for human research biobanking, and to propose a new theory on the
      legal nature of human tissue.

PMID- 22977959
TI  - Genetic privacy and non-discrimination.
AB  - The UN Inter-Agency Committee on Bioethics met for its tenth meeting at the
      UNESCO headquarters in Paris on 4-5th March 2011. Member organisations such as
      the WHO and UNESCO were in attendance alongside associate members such as the
      Council for Europe, the European Commission, the Organisation for Economic Co
      operation and Development and the World Trade Organisation. Discussion centred on
      the theme "genetic privacy and nondiscrimination". The United Nations Economic
      and Social Council (ECOSOC) had previously considered, from a legal and ethical
      perspective, the implications of increasingly sophisticated technologies for
      genetic privacy and non-discrimination in fields such as medicine, employment and
      insurance. Thus, the ECOSOC requested that UNESCO report on relevant developments
      in the field of genetic privacy and non-discrimination. In parallel with a
      consultation process with member states, UNESCO launched a consultation with the
      UN Interagency Committee on Bioethics. This article analyses the report presented
      by the author concerning the analysis of the current contentions in the field and
      illustrates attempts at responding on a normative level to a perceived threat to
      genetic privacy and non-discrimination.

PMID- 22977960
TI  - [On the Decision of the European Court of Human Rights. The S.H. and others
      against Austria. TEDH 2010/56 of April 1, on human assisted reproduction and its
      incidence on the European legislative arena].
AB  - The judgment of ECHR 2010/56 responds positively the appeal on the part of four
      Austrian citizens (two married couples) against the Austrian state. The
      applicants complained that the prohibition of sperm and ova donation for in vitro
      fertilisation as established in the Austrian Law of 1992 amounts to
      discrimination, against article 14 of the European Convention on Human Rights in
      conjunction with article 8, which establishes that everyone has the right to
      respect for his private and family life. After a detailed exposition of the
      circumstances surrounding this case, the author examines the origin of the
      practices of artificial insemination and IVF. The author highlights the
      transcendence of questions linked to extracorporeal fertilisation and human
      embryology and looks at the European regulation and the doctrine of reproductive
      rights, paying attention to the widespread use of the abovementioned techniques
      in the globalised world and the transborder practices in the European
      territories. The author points out that the current implementation of assisted
      reproduction techniques and the lack of uniform regulation in the European
      context might have influenced the above judgment of the ECHR 2010/56, which
      pronounced that the 1992 Austrian Law of Artificial Reproduction was not in
      accordance with article 14 of the European Convention on Human Rights, contrary
      to the judgment passed by the Austrian Constitutional Court eleven years earlier.
      It was not questioned, and so it was established by the ECHR, that the applicants
      right to use assisted reproduction techniques is protected by article 8 of the
      Convention. However, this does not make the estate liable to allow or regulate
      the abovementioned practices as long as this does not result in discrimination.
      According to the author, the right to resort to artificial reproduction
      techniques is contingent and therefore different from the freedom to procreate
      that is inherent to the human person, and covered under the right of men and
      women to marry and found a family warranted by article 12 of the European
      Convention on Human Rights.

PMID- 22977962
TI  - Recommendation CM/Rec (2010)11 of the Committee of Ministers to member states on
      the impact of genetics on the organisation of health care services and training
      of health professionals.

PMID- 22977961
TI  - Genomic research with human samples. Points of view from scientists and research
      subjects about disclosure of results and risks of genomic research. Ethical and
      empirical approach.
AB  - Biomedical researchers often now ask subjects to donate samples to be deposited
      in biobanks. This is not only of interest to researchers, patients and society as
      a whole can benefit from the improvements in diagnosis, treatment, and prevention
      that the advent of genomic medicine portends. However, there is a growing debate
      regarding the social and ethical implications of creating biobanks and using
      stored human tissue samples for genomic research. Our aim was to identify factors
      related to both scientists and patients' preferences regarding the sort of
      information to convey to subjects about the results of the study and the risks
      related to genomic research. The method used was a survey addressed to 204
      scientists and 279 donors from the U.S. and Spain. In this sample, researchers
      had already published genomic epidemiology studies; and research subjects had
      actually volunteered to donate a human sample for genomic research. Concerning
      the results, patients supported more frequently than scientists their right to
      know individual results from future genomic research. These differences were
      statistically significant after adjusting by the opportunity to receive genetic
      research results from the research they had previously participated and their
      perception of risks regarding genetic information compared to other clinical
      data. A slight majority of researchers supported informing participants about
      individual genomic results only if the reliability and clinical validity of the
      information had been established. Men were more likely than women to believe that
      patients should be informed of research results even if these conditions were not
      met. Also among patients, almost half of them would always prefer to be informed
      about individual results from future genomic research. The three main factors
      associated to a higher support of a non-limited access to individual results
      were: being from the US, having previously been offered individual information
      and considering genomic data more sensitive than other personal medical data.
      Moreover, the disease of patients, the educational level and the patient's
      country of origin were factors associated with the perception of risks related to
      genomic information. As a conclusion, it is mandatory to clarify the criteria
      required to establish when individual results from genomic research should be
      offered to participants.

PMID- 22977963
TI  - Werther's syndrome: copycat self-immolation in Israel with a call for responsible
      media response.

PMID- 22977964
TI  - Evaluation of the capacity of inpatients with chronic schizophrenia to provide
      informed consent for participation in clinical trials; use of the Hebrew version
      of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR).
AB  - BACKGROUND: Patient protection requires the provision of informed consent for
      participation in medical research. The MacArthur Competence Assessment Tool for
      Clinical Research (MacCAT-CR) is frequently used for screening the capacity of
      research subjects to consent to participate in research. OBJECTIVES: To evaluate
      the utility of the Hebrew translation of the MacCAT-CR for assessing the capacity
      of patients with chronic schizophrenia to provide informed consent to participate
      in clinical trials. METHODS: We evaluated the translated MacCAT-CR by
      comparingthe capacity of patients with chronic schizophrenia to provide informed
      consent to participate in clinical trials. The following standardized
      neurocognitive assessment tools were used: Addenbrooke's Cognitive Examination
      (ACE) and Frontal Assessment Battery (FAB), as well as the attending doctor's
      assessment. RESULTS: Twenty-one patients participated. Mean MacCAT-CR score was
      12 +/- 10.57 (range 0-32), mean FAB score 9.9 +/- 4.77 (range 1-18), mean ACE
      59.14 +/- 16.6 (range 27-86) and mean doctor's assessment 5.24 +/- 1.18 (range 3
      7). CONCLUSIONS: The Hebrew version of the MacCAT-CR helped identify patients
      with the capacity to provide informed consent for participation in research.
      Patients with FAB scores > or = 12 tended to score higher on the Hebrew version
      of the MacCAT-CR, thus confirming the utility of the Hebrew version of the MacCAT
      CR. During the screening process for clinical trials it may be practical to
      administer the concise FAB questionnaire, and then administer the MacCAT-CR only
      to those who scored > or = 12 on the FAB.

PMID- 22977965
TI  - Human brucellosis outbreak acquired through camel milk ingestion in southern
      Israel.
AB  - BACKGROUND: Human brucellosis is common in southern Israel among the semi-nomadic
      Bedouin, a population that consumes unpasteurized dairy products. Though camel
      milk ingestion is a known mechanism for brucellosis acquisition, only a few
      reports of sporadic cases have been published in the medical literature.
      OBJECTIVES: To describe a local brucellosis outbreak in 15 extended Bedouin
      family members, following ingestion of infected camel milk. METHODS: Data
      regarding patient's clinical manifestations, laboratory findings, treatment and
      outcome were collected from the hospital and the health fund clinics'
      computerized database. Camel's blood and milk were tested for Brucella serology
      and culture. Cases were defined by positive Rose Bengal test, symptoms
      correlating with brucellosis, and consumption of infected camel milk. RESULTS:
      Fifteen patients were diagnosed with acute brucellosis from March to June 2011.
      Sixty percent of cases had serum agglutination test titers of 1:160 or higher and
      4/8 (50%) had positive blood culture for Brucella melitensis. Arthralgia and
      fever were the most consistent clinical manifestations. Blood and milk serology
      and milk culture taken from the female camel were positive for Brucella
      melitensis. CONCLUSIONS: The treating physicians must consider the possibility of
      infected camel milk ingestion as the mode of infection, both in sporadic cases
      and in outbreaks of brucellosis.

PMID- 22977966
TI  - Intraarterial multi-modal reperfusion therapy for acute ischemic stroke: a10 year
      single-center experience.
AB  - BACKGROUND: Only 0.5% of stroke patients in Israel are treated with endovascular
      multi-modal reperfusion therapy (MMRT) each year. OBJECTIVES: To assess our
      experience with MMRT over the last decade. METHODS: We analyzed data from our
      stroke registry of patients undergoing MMRT during 2002-2011. All patients
      underwent multi-parametric imaging studies including subtraction angiography
      according to a predetermined algorithm. Stroke severity was measured with the
      National Institutes of Health Stroke Scale (NIHSS). Disability was measured with
      the modified Ranking Scale (mRS) and classified as favorable (mRS < or = 2) or
      unfavorable. Target vessel recanalization was determined with the thrombolysis in
      myocardial infarction (TIMI) scale. RESULTS: During the study period 204 patients
      were treated; 166 of them had complete data sets including mRS scores at 90 days
      and were included in the analysis. Favorable outcomes at 90 days post-stroke were
      observed in 37% of patients and the mortality rate was 25%. Patients with
      favorable outcomes were younger, had significantly lower NIHSS scores on
      admission and discharge, and more often had complete target vessel recanalization
      (TIMI 3). On regression analysis the only factor associated with favorable
      outcome was TIMI 3, whereas increasing age and NIHSS scores on admission and
      discharge were predictors of poor outcome. CONCLUSIONS: Our data show that MMRT
      can be successfully implemented in patients with severe stroke in Israel. More
      than a third of our patients with severe ischemic strokes who could not receive
      acute treatment were functionally independent after MMRT, demonstrating that this
      procedure is an important alternative for patients who are not candidates for
      intravenous tissue plasminogen activator (tPA) or do not achieve recanalization
      with tPA.

PMID- 22977967
TI  - Anemia associated with acute infection in children.
AB  - BACKGROUND: The pathogenesis of anemia associated with acute infection in
      children has not been well delineated. OBJECTIVES: To characterize this type of
      anemia in children with acute infection, mainly in relation to iron status.
      METHODS: These two cross-sectional studies compared the prevalence and severity
      of anemia between outpatient febrile children and age-matched non-febrile
      controls. RESULTS: In part 1 of the study, children with acute infection (n = 58)
      had a significant decrease in hemoglobin levels compared with 54 non-febrile
      controls. Mean corpuscular volume (MCV) did not change this association.
      Moreover, there was no significant difference in MCV, mean cell hemoglobin or red
      cell distribution width values between the two groups. Regarding part 2, of the
      6534 blood counts obtained in community clinics, 229 were defined as "bacterial
      infection." Chart survey confirmed this diagnosis. White blood cell level was
      significantly inversely associated with hemoglobin level (r = -0.36, P < 0.0001).
      Anemia was significantly more prevalent among children with bacterial infection
      compared to those without: 21.4% vs. 14.1% (P = 0.002). Mean values of iron
      status parameters were all within normal limits. CONCLUSIONS: Acute illness is
      associated with anemia. The pathogenesis of this anemia does not appear to be
      associated with disruption of iron metabolism.

PMID- 22977968
TI  - Clinical experience of two Israeli medical centers with the implantable loop
      recorder in patients with syncope: from diagnosis to treatment.
AB  - BACKGROUND: The implantable loop recorder (ILR) is an important tool for the
      evaluation of unexplained syncope, particularly in cases of rarely occurring
      arrhythmia. OBJECTIVES: To review the clinical experience of two Israeli medical
      centers with the ILR. METHODS: We reviewed the medical records of patients with
      unexplained syncope evaluated with the ILR at Rabin Medical Center (2006-2010)
      and Wolfson Medical Center (2000-2009). RESULTS: The study group included 75
      patients (44 males) followed for 11.9 +/- 9.5 months after ILR implantation.
      Patients' mean age was 64 +/- 20 years. The ILR identified an arrhythmic
      mechanism of syncope in 20 patients (17 bradyarrhythmias, 3 tachyarrhythmias) and
      excluded arrhythmias in 12, for a diagnostic yield of 42.7%. It was not
      diagnostic in 17 patients (22.7%) at the time of explant; 26 patients (34.7%)
      were still in follow-up. In two patients ILR results that were initially negative
      were reversed by later ILR tracings. The patients with bradyarrhythmias included
      9 of 16 (56.3%) with surface electrocardiogram conduction disturbances and 2 of
      12 (16.7%) with negative findings on carotid sinus massage. All bradyarrhythmic
      patients received pacemakers; the seven patients for whom post-intervention data
      were available had no or mild symptoms. CONCLUSIONS: The ILR has a high
      diagnostic yield. Pre-ILR findings correlating with the ILR results are
      conduction disturbances (positive predictor of arrhythmia) and negative carotid
      sinus massage results (negative predictor of arrhythmia). Proper patient
      instruction is necessary to obtain accurate results. Caution is advised when
      excluding an arrhythmia on the basis of ILR tracings, and long-term follow-up is
      warranted.

PMID- 22977969
TI  - The predictive value of P-wave duration by signal-averaged electrocardiogram in
      acute ST elevation myocardial infarction.
AB  - BACKGROUND: The prognostic value of P-wave duration has been previously evaluated
      by signal-averaged ECG (SAECG) in patients with various arrhythmias not
      associated with acute myocardial infarction (AMI). OBJECTIVES: To investigate the
      clinical correlates and prognostic value of P-wave duration in patients with ST
      elevation AMI (STEMI). METHODS: The patients (n = 89) were evaluated on the
      first, second and third day after admission, as well as one week and one month
      post-AMI. Survival was determined 2 years after the index STEMI. RESULTS: In
      comparison with the upper normal range of P-wave duration (<120 msec), the P-wave
      duration in STEMI patients was significantly increased on the first day (135.31
      +/- 29.29 msec, P < 0.001), up to day 7 (127.17 +/- 30.02 msec, P = 0.0455). The
      most prominent differences were observed in patients with left ventricular
      ejection fraction (LVEF) < or = 40% (155.47 +/- 33.8 msec), compared to LVEF >
      40% (128.79 +/- 28 msec) (P = 0.001). P-wave duration above 120 msec was
      significantly correlated with increased complication rate; namely, sustained
      ventricular tachyarrhythmia (36%), congestive heart failure (41%), atrial
      fibrillation (11%), recurrent angina (14%), and re-infarction (8%) (P = 0.012,
      odds ratio 4.267, 95% confidence interval 1.37-13.32). P-wave duration of 126
      msec on the day of admission was found to have the highest predictive value for
      in-hospital complications including LVEF 40% (area under the curve 0.741, P <
      0.001). However, we did not find a significant correlation between P-wave
      duration and mortality after multivariate analysis. CONCLUSIONS: P-wave duration
      as evaluated by SAECG correlates negatively with LVEF post-STEMI, and P-wave
      duration above 126 msec can be utilized as a non-invasive predictor of in
      hospital complications and low LVEF following STEMI.

PMID- 22977970
TI  - Ethical challenges posed by trisomy 18 infants.

PMID- 22977971
TI  - Laboratory tools for diagnosis and monitoring response in patients with chronic
      myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a clonal hematological disease that represents
      15-20% of all adult leukemia cases. The study and treatment of CML has
      contributed pivotal advances to translational medicine and cancer therapy. The
      discovery that a single chromosomal abnormality, the Philadelphia (Ph)
      chromosome, is responsible for the etiology of this disease was a milestone for
      treating and understanding CML. Subsequently, CML became the first disease for
      which allogeneic bone marrow transplantation is the treatment of choice.
      Currently, CML is one of the few diseases where treatment targeted against the
      chromosomal abnormality is the sole frontline therapy for newly diagnosed
      patients. The use of directed therapy for CML challenged disease monitoring
      during treatment and led to the development of definitions that document response
      and predict relapse sooner than the former routine methods. These methods relied
      on classical cytogenetics through molecular cytogenetics (FISH) and, finally, on
      molecular monitoring assays. This review discusses the laboratory tools used for
      diagnosing CML, for monitoring during treatment, and for assessing remission or
      relapse. The advantages and disadvantages of each test, the common definition of
      response levels, and the efforts to standardize molecular monitoring for CML
      patient management are discussed.

PMID- 22977972
TI  - Novel biological treatments for systemic lupus erythematosus: current and future
      modalities.
AB  - Current treatments for systemic lupus erythematosus (SLE) are effective in
      reducing morbidity and mortality but are not specific and have severe adverse
      effects. Based on understanding of the different dysregulated immunological
      pathways involved in SLE pathogenesis, specific targeted therapies were
      developed. This review presents the current and the near-future novel biological
      immune targeted treatments, such as B cell-targeted therapy, cytokine blockade,
      peptide-based treatments and other novel treatments for SLE.

PMID- 22977973
TI  - Trisomy 18: how far should we go.

PMID- 22977974
TI  - Autoimmune progesterone anaphylaxis in a 24 year old woman.

PMID- 22977975
TI  - Primitive neuroectodermal tumor of the kidney with renal failure.

PMID- 22977976
TI  - Cushing's syndrome as a harbinger of relapsed nonsmall cell lung cancer.

PMID- 22977977
TI  - Laparoscopic cholecystectomy in a left ventricular assist device-supported
      patient.

PMID- 22977978
TI  - An inconvenient truth -- office based surgery.

PMID- 22977979
TI  - Prevention is the best prescription.

PMID- 22977980
TI  - ICD-10. Now is not the time to implement, now is the time to learn!

PMID- 22977981
TI  - Short history of obstetrics in Little Rock 1963 to 2012.

PMID- 22977982
TI  - Gluten sensitivity: fad and fact.

PMID- 22977983
TI  - Prolonged period of acute bronchitis with late progression to acute respiratory
      distress syndrome as possible result of influenza A (H1N1) virus infection.
AB  - Young adults with underlying medical conditions who are infected with the H1N1
      virus are at risk of quickly progressing from mild upper airways infection to
      severe ARDS within 4 to 5 days after the onset of the illness. Here, we report
      the case of a 46-year-old morbidly obese and diabetic woman infected with the
      H1N1 virus who developed acute bronchitis that lasted for 4 weeks and then
      progressed to ARDS. We discuss the month-long persistence of the H1N1 viral
      bronchitis and its late progression to ARDS which may reflect prolonged viral
      activity. Such a prolonged, rather than quick, course of deterioration can cause
      clinicians to misdiagnose the etiology of the ARDS and may cause the patient to
      receive a prolonged treatment with steroids to treat bronchitis symptoms. These
      steroids may cause increased viral replication and promote parenchymal
      involvement and the development of ARDS.

PMID- 22977984
TI  - Total body irradiation.

PMID- 22977985
TI  - Health care and obesity: can we really have our cake and eat it, too?

PMID- 22977986
TI  - Renal cell carcinoma: a reappraisal.
AB  - Surgical treatment of renal cell carcinoma is the gold standard. Nephron-sparing
      surgery, laparoscopic and robotic surgery and minimally invasive procedures have
      decreased the morbidity of treatment. Although traditionally resistant to
      chemotherapy and radiation therapy, advances have been made with immunotherapies.
      Physicians and nurses caring for patients with renal cell carcinoma should be
      aware of changes in management and newer therapies for treatment of advanced
      disease.

PMID- 22977987
TI  - Traces: making sense of urodynamics testing--part 12: videourodynamics testing.
AB  - Videourodynamics testing combines radiographic images of the lower urinary tract
      with physiologic tracings from multichannel urodynamics testing to provide a more
      comprehensive evaluation of lower urinary function than either modality completed
      alone. Part 12 of the Traces series describes the role of videourodynamics
      testing in evaluation of the lower urinary tract and its unique contribution to
      the diagnosis of specific lower urinary tract disorders.

PMID- 22977989
TI  - Prevention of incontinence-related skin breakdown for acute and critical care
      patients: comparison of two products.
AB  - Perineal protection products were compared for their efficacy in preventing skin
      breakdown in the hospitalized patient with urinary and/or fecal incontinence.
      Each product was used for the duration of the hospital stay with daily
      observations for perineal skin condition. Results indicated the spray product and
      wipe product were comparable in rate of skin breakdown prevention. Findings
      suggest the wipe product is more cost-effective for use during hospitalization,
      and the spray product preserves skin integrity over a longer period of time,
      beyond average hospitalization duration.

PMID- 22977988
TI  - Nursing home staff members' attitudes and knowledge about urinary incontinence:
      the impact of technology and training.
AB  - Urinary incontinence (UI) poses challenges for nursing home personnel. The
      authors of this study explored differences in attitude and knowledge about UI
      among registered nurses, licensed practical nurses, and certified nursing
      assistants working in skilled nursing homes before and after study interventions.

PMID- 22977990
TI  - Statistics on homelessness are grim.

PMID- 22977991
TI  - Amazing student experience.

PMID- 22977992
TI  - Unethical professional conduct.

PMID- 22977993
TI  - Two sides to a story.

PMID- 22977994
TI  - Towards 100% renewable energy.

PMID- 22977995
TI  - Safety is priority.

PMID- 22977996
TI  - Industrial.

PMID- 22977997
TI  - AINs: part of the nursing family.

PMID- 22977998
TI  - Gardening to improve wellbeing.

PMID- 22977999
TI  - Implementing a respiratory education module (REM), bedside assessments and
      competencies in a ward based respiratory care unit.

PMID- 22978000
TI  - In search of our founder.

PMID- 22978001
TI  - Minors and refusal of treatment: who decides in the best interests of the child?

PMID- 22978002
TI  - Mental health focus, the lifesaver.

PMID- 22978003
TI  - Stimulating an interest in mental health nursing.

PMID- 22978004
TI  - To do or not to do that is the dilemma?

PMID- 22978005
TI  - Affordable and appropriate housing: a necessary component of mental health care.

PMID- 22978006
TI  - "Last night a Xanax saved my life".

PMID- 22978007
TI  - Physical health of people with mental illness: time for action.

PMID- 22978008
TI  - Insecure work--a growing tragedy.

PMID- 22978010
TI  - [Glusosamine preparations in the community pharmacy -- introduction].

PMID- 22978011
TI  - [Is there a place for glucosamine in the community pharmacy?].
AB  - Glucosamine is a popular treatment for osteoarthritis. Despite of the ongoing
      debate around its efficiency, the sale of glucosamine is a success in pharmacies.
      The molecule remains issue of controversy: while some studies provide proof of
      its efficiency, other studies and meta-analysis are unable to answer the question
      or don't find any advantage. This article treats the current state of glucosamine
      regarding its efficiency and safety and aims to trigger the pharmacy-team to help
      the patient evaluating the product after three months of use.

PMID- 22978009
TI  - [Self-medication of regular headache: a community pharmacy-based survey in
      Belgium].
AB  - AIM: This observational community pharmacy-based study aimed to investigate
      headache characteristics and medication use of persons with regular headache
      presenting for self-medication. METHODS: Participants (n=1205) completed ii) a
      questionnaire to assess current headache medication and previous physician
      diagnosis, (ii) the ID Migraine Screener [ID-M] and (iii) the MIDAS
      questionnaire. RESULTS: Forty-four % of the study population (n=528) did not have
      a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were
      found to be ID-M positive. The most commonly used acute headache drugs were
      paracetamol (used by 62% of the study population), NSAIDs (39%) and combination
      analgesics (36%). Only 12% of patients physician-diagnosed with migraine used
      prophylactic migraine medication, and 25% used triptans. About 24% of our sample
      (n=292) chronically overused acute medication, which was combination analgesic
      overuse (n=166), simple analgesic overuse (n=130), triptan overuse (n=19), ergot
      overuse (n=6) and opioid overuse (n=51). Only 14.5% was ever advised to limit
      intake frequency of acute headache treatments. CONCLUSIONS: This study identified
      underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and
      high prevalence of medication overuse among subjects seeking self-medication for
      regular headache. Community pharmacists have a strategic position in education
      and referral of these self-medicating headache patients.

PMID- 22978013
TI  - [What can the pharmacist do for a patient with heart failure?].
AB  - Heart failure is a chronic and progressive pathology. Its prevalence is
      increasing due to aging of the population and improved care for patients with
      cardiovascular disease. This pathology is responsible of very significant costs,
      particularly because of frequent hospitalizations of patients. Heart failure
      cannot be cured, but can be effectively treated. The treatment aims to improve
      the quality of life of the patient by controlling the symptoms of the disease and
      prolongs life by slowing disease progression. Treatment will consist not only in
      good drug therapy, but also in educating the patient about his illness and his
      treatment. This article presents some important elements that the pharmacist must
      remember to provide optimal care to his patients with heart failure.

PMID- 22978012
TI  - [Glucosamine preparations on the Belgian market: a comparative study].
AB  - Fourteen food supplements and one medicine containing glucosamine and formulated
      as film-coated tablets and capsules, were evaluated with different tests,
      including uniformity of mass and dosage units, disintegration, identification and
      assay of glucosamine with a validated HPLC-ELSD method. The medicinal product
      fulfilled all the fixed requirements whereas three food supplements didn't comply
      with regard to disintegration (product 7) and content of glucosamine (product 11
      and 13).

PMID- 22978014
TI  - [Boceprevir (Victrelis), oral administration].

PMID- 22978015
TI  - [Moxifloxacin (Kanavig), ophthalmic administration].

PMID- 22978016
TI  - Aging well with diabetes.

PMID- 22978017
TI  - Foot care Q & A. Part 1.

PMID- 22978018
TI  - Enjoying healthy eating. Vegetables.

PMID- 22978020
TI  - Supermarket smarts. Meal starters.

PMID- 22978019
TI  - How much do you know about beverages?

PMID- 22978022
TI  - Recipe makeovers. Baked beans.

PMID- 22978021
TI  - Weight-loss programs for people with diabetes.

PMID- 22978023
TI  - Learning self-compassion. A tool for your diabetes management kit.

PMID- 22978024
TI  - Intra-and interexaminer reproducibility of measurements in cone-beam computed
      tomography.

PMID- 22978025
TI  - "After" math: the impact and influence of incentives on benefit policy.

PMID- 22978026
TI  - Anthony DeFurio: achieving growth through partnerships.

PMID- 22978027
TI  - Uncertainty dominates the near-term environment.

PMID- 22978028
TI  - 5 ways to teach physicians about financial management.

PMID- 22978029
TI  - Shared governance: one way to engage employed physicians.
AB  - To work better with employed physicians, finance leaders should: Understand
      classic management theories on what motivates employees. Learn from shared
      governance models with nurses at Magnet hospitals. Apply best practices in
      management to all employees, not just physicians.

PMID- 22978030
TI  - Think big, act small.
AB  - As hospitals and health systems grow, they need to focus on the smallest unit of
      service-the patient visit. Physicians and managers should have the authority and
      accountability that allows them to work together at the local level to serve
      patients and solve operational issues. As long as patients and physicians have a
      choice, the delivery of medical services will be an individual relationship
      business.

PMID- 22978031
TI  - Maintaining revenue cycle health during IT change.

PMID- 22978032
TI  - Sharp healthcare: a smarter plan to help the uninsured.
AB  - Sharp HealthCare partnered with a not-for-profit patient advocacy organization to
      develop a tool for determining its self-pay patients' eligibility to receive
      healthcare coverage. Under the partnership, Sharp has made a "health coverage
      eligibility quiz" developed by the not-for-profit available to patients, which
      patients can use to obtain a personalized list of healthcare coverage options.
      Hospitals that adopt a similar program may find that a high percentage of self
      pay accounts that had previously represented lost revenue are actually eligible
      to be covered under various government and other programs for uninsured patients.

PMID- 22978033
TI  - Bridging the gap between financial reporting and the revenue cycle.
AB  - Implementing a standardized financial reporting and revenue cycle monitoring
      platform can help healthcare organizations improve their net revenue reporting
      and budgeting processes. Consistent, standardized data help the finance office
      estimate accounts receivable reserves more accurately, streamline the month-end
      closing process, and strengthen internal controls. The benefits of standardizing
      the finance and revenue cycle functions are particularly significant in large
      organizations with multiple facilities, but even single-facility providers can
      benefit from improved communication between the business office and finance.

PMID- 22978034
TI  - Leveraging existing technology to boost revenue cycle performance.
AB  - Revenue cycle leaders can reduce the frequency or level of technology investment
      needed while maintaining strong service and payment accuracy by looking at four
      areas of opportunity: Applying output from existing technology in new ways
      Seeking new functionality from existing systems. Linking with external systems to
      provide greater capabilities. Supplementing limitations of existing technology
      with outside expertise.

PMID- 22978035
TI  - Strategies for ICD-10 implementation.
AB  - Hospitals and health systems should consider seven strategies for preparing for
      the conversion from ICD-9-CM to ICD-10-CM/PCS: Form a project planning team.
      Assess the range of impact on each department and on productivity, revenue, and
      resources. Perform a gap analysis. Analyze data. Develop a training strategy
      specific to coding professionals and heavy data users. Work to improve
      documentation. Communicate with vendors regarding their plans for the transition
      to ICD-10.

PMID- 22978036
TI  - The clinical documentation advantage protecting the revenue cycle under ICD-10.
AB  - Healthcare providers need to prepare their revenue cycles for the profound
      increase in coding complexity and detail that will result from the transition to
      ICD-10. The best strategy for providers to build a solid foundation for effective
      ICD-10 coding, and thereby protect the revenue cycle, is to establish a clinical
      documentation improvement (CDI) program. CDI specialists will need to work with
      physicians to ensure the level of specificity required for ICD-10 coding is
      included in the clinical documentation.

PMID- 22978037
TI  - Achieving revenue integrity in hospitals and health systems.
AB  - The Bellevue Hospital sought to improve its performance in three areas-days in
      accounts receivable (A/R), denials, and charge capture-to enhance revenue
      integrity. Results included the following: A 30-percent reduction in days in A/R.
      A nearly 200 percent increase in bad debt collections. A more than $1.6 million
      reduction in denials write-offs. An improvement in net revenue of more than $1
      million.

PMID- 22978038
TI  - Choosing the right strategy for point-of-service collections.
AB  - Healthcare organizations should keep three key considerations in mind when
      selecting and implementing a pricing transparency tool: The approach that the
      tool will take (e.g., claims-based or contract-based). The training required of
      staff. The benchmarks that will be used to measure performance, ROI, and
      satisfaction of patients and staff.

PMID- 22978039
TI  - Long-term incentive pay plans: a value option for healthcare organizations.
AB  - Long-term incentives allow organizations to reward certain executives for
      performance without increasing base salaries or annual incentives. When designing
      long-term incentive packages, organizations should: Focus primarily on strategic
      goals spanning multiple years. Ensure that long-term goals are supportive, yet
      not duplicative of annual goals. Balance financial imperatives with longer-term
      quality and satisfaction initiatives

PMID- 22978040
TI  - Top 5 takeaways from HFMA's 2012 MAP Award winners.

PMID- 22978041
TI  - Risky business.

PMID- 22978042
TI  - Investment returns: on a treadmill in 2011.

PMID- 22978043
TI  - The dollar trends of hospital revenue cycle management.

PMID- 22978044
TI  - [Fate of the results of research projects].
AB  - Once completed, the results of a research project must be made known to the
      scientific community. This is usually achieved by presentations at scientific
      meetings or by publishing the results in a journal of the specialty. The purpose
      is not only to make public these findings, but that they can be used to solve
      problems, immediately or in the long-term, or to serve as the basis for future
      research. However, several studies have found that less than 50% of the
      communications to congresses are published. One of the main reasons is that
      publications in high impact journals can not be easily attained since most of
      them are not of open access. For this reason, it is convenient to resort to free
      access journals listed in prestigious international indexes. The Council for
      Scientific Development at the University of Zulia financially supports a number
      of scientific journals that meet these criteria. If the research was the result
      of a PhD, Master or Specialty thesis or the project for a promotion in an
      academic institution, the end result should be also their publication; but
      commonly, these are even less published than communications to scientific
      meetings. At the University of Zulia, Serbiluz has made a major effort to collect
      all this material and make it available to serve the scientific community. It is
      necessary to mention that the institution that supports financially a research
      project has the right to demand its publication, to benefit the greatest number
      of people and as a mean to compensate the economic support with scientific
      knowledge.

PMID- 22978045
TI  - [Musculoeskeletal symptoms in bus drivers of a university institution].
AB  - Musculoskeletal symptoms (MSDs) in bus drivers have been associated to the
      inadequate conditions of the work station. The occurrence of MES was determined
      in the total population of bus drivers of a public university (N = 35), and these
      were related with the work station, the posture static load, age, BMI, worked
      days and the number of years in the position. In this study, the age range was
      between 27 and 56 years. The standardize Nordic Musculoskeletal Questionnaire for
      the determination of the MSDs, the method of the Regie National Des Usines
      Renault to measure the static postural load and a questionnaire to collect
      information of the bus working conditions were applied. The mean (X +/- SD) age
      was 39 +/- 1.94 years and the body mass index (BMI) was 31 +/- 1.95 Kg/m2. The
      MSDs were associated significantly to the BMI (rs = 0.895 and p < 0.05). There
      was a high incidence of MSDs (94%) with more occurrences in neck (69%), lower
      back (60%), superior back (57%) and knees (43%). Pain of strong intensity,
      located in the lower back and knees, was the main symptom. These findings can be
      related with the risks at the work station, such as absence of head support,
      lumbar support, non sliding seat and inadequate conditions of the labor
      environment: vibration and noise. There was neither association nor correlation
      of MSDs and the postural static load, or with the others variables in study. The
      results suggest that inadequate conditions of the work stations as well as the
      BMI, dominated the occurrence of MSDs.

PMID- 22978046
TI  - [Mycoplasmas and antibodies anti-Chlamydia in semen of infertile men and their
      relationship with seminal quality and markers of male accessory sex glands].
AB  - Male infertility may be due to inflammation or infection of the genital tract
      among other causes. Male accessory sex glands and sperm function may also be
      involved in the problem of infertility. This study tries to associate the most
      frequent bacteria in semen of infertile men including Chlamydia trachomatis,
      Mycoplasma hominis and Ureaplasma urealyticum with the seminal characteristics
      and levels of fructose, citric acid and alpha-neutral glucosidase as markers of
      the accessory glands. Detection of antibodies anti Chlamydia trachomatis
      indicated that it was the most prevalent germ. Antibodies (Ab) anti-Chlamydia,
      Mycoplasma hominis and Ureaplasma urealyticum were associated with a decrease of
      the glandular markers fructose and alpha-neutral glucosidase. On the other hand,
      there were increased pH and leukocytospermia in men positive for antibodies anti
      Chlamydia. Microbiological and biochemical evaluation of semen could orient more
      about the spread of infection and allow for the selection of the most effective
      therapy. We find that microbiological and glandular accessory markers assessments
      in semen are important to diagnose and to treat infections.

PMID- 22978047
TI  - [Usefullness of the Kramer's index in the diagnosis of hyperbilirubinemia of the
      newborn].
AB  - The objective of the present study was to correlate seric values of bilirubin
      with the Kramer's index in a group of newborns with neonatal jaundice, from three
      different ethnic groups. This was a prospective, randomized, observational,
      descriptive-analytical, longitudinal, comparative and controlled study of 50
      newborns with neonatal jaundice, without complications. They were divided into
      three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local
      indigenous descent (Wayuu) and C, n = 10, of Afro-American descent. Each newborn
      was screened at the start of the study for their Kramer's dermic areas and
      simultaneously, a venous blood sample from the arm was taken for bilirubin
      quantification. They were compared through a correlation-regression analysis.
      Values at the beginning of the study were: serum bilirubin 12.02 +/- 3.41 mg/dL,
      and 62.8% of neonates were at Kramer's level 3. There were no differences among
      the ethnic groups studied and the correlation bilirubin/Kramer's index was r=
      0.93 (p < 0.005). At the third day, both bilirubin and Kramer's indexes started
      to decrease. There were no ethnic differences. In conclusion, the Kramer's method
      offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non
      invasive method with no cost. Besides, it is of great help in the prevention of
      the kernicterus. It is recommended to implement the use of the Kramer method in
      all the newborns units in our Hospitals, preferably in those lacking
      transcutaneous bilirubinometers.

PMID- 22978048
TI  - Fas and FasL expression in leukocytes from chronic granulomatous disease
      patients.
AB  - Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency
      characterized by defects in superoxide (O2-) production, which result from
      mutations in one of the four NADPH oxidase components, predisposing to bacterial
      and fungal infections. Besides the O2-defect, it has been described that
      neutrophils from CGD patients are resistant to cell death, a phenomenon that has
      been connected to chronic inflammation and predisposition to autoimmune diseases.
      A diminished expression of Fas and its counterpart FasL, molecules known to play
      a major role in cell death, has been described in lymphocytes depleted of O2
      reactive oxygen species (ROS), suggesting an involvement of ROS in Fas/FasL
      expression. In this work, Fas and FasL expressions were analyzed in T cells and
      neutrophils from two CGD families, previously known to harbor two different
      molecular defects: absence of either p47-phox or p67-phox. We found that T
      lymphocytes from CGD patients express low levels of Fas and FasL, while a
      diminished FasL expression was observed on neutrophils from a CGD A470 patient.
      These defects may contribute to understand altered cell death in CGD patients.

PMID- 22978049
TI  - [Diagnosis of Helicobacter pylori infection by PCR in gastric juice and
      gastroesophageal biopsies from dyspeptic patients].
AB  - Helicobacter pylori is the main bacterial agent implicated in human
      gastroduodenal inflammatory pathologies; being one of the most common bacterial
      pathogens, with a high prevalence in Venezuela. The diagnosis of H. pylori
      infection is performed primarily in gastric biopsies through PCR; however, string
      absorbed gastric juice and esophageal biopsies could be also used as alternative
      specimens to determine the infection. In this study the H. pylori infection was
      assessed in different specimens of the upper tract digestive of dyspeptic
      patients, though the detection by PCR of essential genes (glmM and ureA) and
      genes encoding virulence factors (cagA). Of 104 patients studied, H. pylori was
      found in 53.8, 69,2 and 58,7% of gastric juice, and gastric and esophageal
      biopsies, respectively; with predominance of the strains type I (cagA+) in juice
      and gastric biopsies, and strains type II (cagA-) in esophageal biopsies. The
      detection of H. pylori in gastric juice and esophageal biopsies showed high
      sensitivity and specificity, in comparison with the detection in gastric
      biopsies, suggesting that both types of specimens may be used efficiently for a
      secure diagnosis of H. pylori infection.

PMID- 22978050
TI  - [Prevalence of cytomegalovirus infection in pediatric patients with neurological
      disorders in Zulia state, Venezuela (2007-2008)].
AB  - The aim of this study was to determine the prevalence of cytomegalovirus (CMV) in
      pediatric patients with neurological disorders from Zulia State, Venezuela,
      during the period 2007-2008. Samples of cerebrospinal fluid (CSF) and serum were
      obtained from 186 patients with neurological symptoms and bacteriological
      negative CSF. The albumin CSF/serum content was determined to rule out
      contamination of CSF and optimal pairs were determined by ELISA of IgM and IgG
      anti-CMV antibodies in serum and IgG in CSF. Only 40.86% (76/186) of patients
      were optimal for this study. Serum samples positive for IgM antibodies (2/76;
      2.6%) and IgG antibodies (71/76; 93.4%) were obtained. CSF IgG antibodies were
      observed in 24/76 patients (31.6%). Increased values of glucose in CSF (p < 0.05)
      were observed in 58.3% of CMV patients with meningoencephalitis. In addition,
      increased CSF protein concentration (p < 0.01) was observed in CSF anti-CMV
      antibodies positive patients with meningitis. This study shows high prevalence of
      acute CMV infection in pediatric patients with neurological affections suggesting
      an important role of this virus in this pathology during the studied period.

PMID- 22978051
TI  - [Effect of congenital infection by Trypanosoma cruzi on intrauterine development
      and the fetal-neonatal immune response].
AB  - In congenital infection by Trypanosoma cruzi, morbidity and mortality vary from
      asymptomatic cases to severe clinical forms of the disease. It has been found
      that there is no specific clinical profile in newborns infected by T. cruzi,
      since during intrauterine development diverse pathological changes take place,
      causing alterations in the serological and parasitological profiles. Some
      intrinsic factors of the host, such as: the placental barrier and the ability of
      both, mother and fetus, to develop a specific immune response to control parasite
      multiplication, could be involved in such differences. Another possibility
      includes the genetic polymorphism of T. cruzi, since it is considered that
      strains of greater virulence can cross the placenta more easily and are more
      pathogenic to the fetus and/or the neonate.

PMID- 22978052
TI  - [Limbal deficiency syndrome].
AB  - The cornea, the transparent tissue of the eye, is formed by an epithelium of five
      distinct layers that is in continual renewal through a population of limbocorneal
      stem cells located in the basal layer. Its normal activity depends on a variety
      of intrinsic and extrinsic factors, that altered, can lead to partial or total
      loss of progenitor cells leading to a progressive loss of vision. This article
      reviews the importance of this crippling disease, constituting a major health
      problem. Several techniques have been developed, but the transplant of the limbus
      using autograft or allograft accompanied by a treatment to suppress inflammation
      and neovascularization is still the most widely used. At present, this procedure
      is being replaced by the new techniques of tissue engineering, which have
      multiple benefits, such as more safety, efficiency, elimination of the risks of
      rejection, decrease of time of treatment and lower costs. The use of limbal cells
      cultures has made possible to develop a more secure and refined technology. In
      this review we emphasize one of these techniques, which has proven to be very
      effective and advantageous to produce the epithelium of the cornea in vitro.

PMID- 22978053
TI  - The value of the calcium binding protein S100 in the management of patients with
      traumatic brain injury.
AB  - BACKGROUND: From the first study in 1995 the role of calcium-binding protein
      S100B in Traumatic Brain Injury (TBI) has been variously investigated in many
      clinical works. The aim of this work is to analyze the recent published reports
      with a reference to serum and CSF levels and to identify a possible role of S100
      in the management ofTBI. METHODS: A MEDLINE search with a various number of query
      related to "S100" and "TBI" was performed from 2000 to 2011. All identified
      articles and abstracts have been reviewed. RESULTS: Serum and CSF samples of the
      marker well correlate in most of the papers to the degree of intracranial injury
      as determined by CT scans. Furthermore patients with the higher levels of S100B
      show a worse prognosis. In the paediatric age a relationship with the outcomes in
      spite of difficulties to determine normal values is also observed. Some proposal
      about a clinical use of S100B to decrease the number of neuroradiological
      examinations are present. CONCLUSIONS: S100B shows some interesting
      potentialities, but we have not enough evidence to insert this marker of brain
      damage in the protocols for management of TBI. However its use in experts' hands
      in association with others clinical and radiological features may help to improve
      medical practice in the treatment of TBI.

PMID- 22978054
TI  - Functional foods in genomic medicine: a review of fermented papaya preparation
      research progress.
AB  - "Functional foods" represent an emerging opportunity and they will certainly play
      a consistent and important role in future too. Such a new perspective entirely
      depends on the growing attention paid by nutritionists to the development of new
      innovating solutions aiming at acting on organic systems as well as on more
      general topics relating to consumer good health conditions. Differently from the
      past, when mainly retrospective epidemiological studies or empirical experiences
      were carried out on single nutrients, such a new and growing interest by the
      scientific community follows research deeply oriented to clinics supplemented by
      an accurate study on nutrients, genomics and single nutritional requirement
      diagnostics. Already in 1993, the leading journal Nature published a report
      "Japan is exploring limits between food and medicine" (Swinbanks 1993). Clearly
      the success of "Functional foods" depends on the food industry capacity too of
      developing new effective products which on the one side meet any consumer request
      and on the other must be have positive effects on health, supported and validated
      by scientific research and therefore far beyond simple positive properties, as
      recently underlined in a meeting, organised by a no profit non governmental
      international association.

PMID- 22978055
TI  - Children with type 1-diabetes from ethnic minorities: vulnerable patients needing
      a tailored medical support.
AB  - BACKGROUND AND AIM: Newly diagnosed children with type 1 diabetes from ethnic
      minorities are a growing presence in outpatient pediatric clinics, and are
      reported as a group at risk of poor metabolic control. In the present study we
      investigated the barriers affecting chances of minority diabetic children to
      achieve the same metabolic targets of native peers with type 1 diabetes.
      MATERIALS AND METHODS: The study investigated 35 children from ethnic minorities
      (group 1) admitted to the Children University Hospital of Parma, Italy, from 1st
      January 2000 to December 31st, 2011, and data concerning current age, gender,
      ethnicity, age at diabetes onset, HbA1c, DKA severity degree at diagnosis,
      insulin therapy, annual number of out patient clinic visits, number of admissions
      for acute decompensation, and treatment cost. A short questionnaire on
      background, family situation, difficulties in diabetes monitoring, and outpatient
      clinic procedures completed the study. The results were compared with data
      collected from 30 matched native peers (group 2). RESULTS: Mean HbA1c level at
      admittance was higher in Group 1 (11.8 +/- 1.0%) than in Group 2 (9.0 +/- 2.2%;
      p=0.000). The differences were confirmed when HbAlc mean cumulative values (8.6
      +/- 2.1 vs 7.6 +/- 1.1; p=0.022) were calculated. Group 1 children at admission
      showed poorer metabolic conditions and longer stay at hospital (16 +/- 3 days)
      than Group 2 patients (8 +/- 2 days; p=0.000). The total costs for DKA treatment
      and family education resulted higher in group 1 (+54%) than in group 2 patients.
      Discontinuous capillary blood glucose monitoring and outpatient clinic visits
      missed were more frequent in Group 1 than in group 2 patients. Thirteen patients
      in group 1 needed a re-admittance to hospital because of a hypoglycemia (5 cases)
      or a hyperglycemia (8 cases). The same episodes were not recorded in group 2
      patients. Most of parents expressed the wish to be supported with educational
      material in their own language. CONCLUSIONS: Children with TDM belonging to an
      ethnic minority had poorer metabolic control compared with native patients. This
      results from several cultural, educational, economic deficiencies which influence
      their family life and probably reduced their chances to obtain a better control.

PMID- 22978056
TI  - Intestinal immune-potentiation by a purified alkylglycerols compound.
AB  - Alkylglycerols have shown immune stimulant and adjuvant activity in several
      studies and the aim of the present research was to assess in particular the
      effect of shark liver-derived alkylglycerols on gut immune system. C57BL/6 mice,
      fed under specific pathogen free conditions, were randomly divided into two
      groups: (a) fed normal laboratory food or (b) added with alkylglycerols (2
      mg/day/mouse) for 3 weeks. Intraepithelial lymphocytes (IEL) were retrieved from
      the small intestine and tested for NK and tumor cytotoxicity. Lymphocytes from
      liver, spleen and IEL were also assessed as for their counting and phenotypic
      characterization. Under supplementation with alkylglycerols, the number of
      lymphocytes yielded by the small intestine increased by to almost 40%. Moreover,
      the ratio of CD8alphabeta+TCRalphabeta+ cells/CD8alphaalpha+TCRalphabeta+ cells
      remarkably increased. In parallel with this reshaping in the distribution of
      lymphocyte subsets, tumor cytotoxicity of IEL against P815 cells and cytokine
      production from circulating lymphocytes were also enhanced. These data show that
      phylogenetically developed lymphocytes (CD8alphabeta, TCRalphabeta+) were
      significantly activated by the oral administration of alkylglycerols. The present
      results indicate that purified alkylglycerols might have such significant
      potential via the enhancement of intestinal immunity, especially in the small
      intestine.

PMID- 22978057
TI  - Compartment syndrome after viper-bite in toddler: case report and review of
      literature.
AB  - Snakebites in Italy are a rare source of severe medical condition, except in case
      of venomous snakes. The venom causes both local and/or systemic complication
      which may determine death in 6-60 hours, particularly in children and the
      elderly. In fact, the same amount of venom affects children more severely than
      adults because of the reduced total dilution volume in children. The only
      specific and conflicting therapy for venomous snakebite is to administer the
      appropriate anti-venom; the remaining therapy is symptomatic and supportive. We
      describe the case of a 22-month-old child who, despite appropriate symptomatic
      treatment, developed severe signs and an acute compartment syndrome of the right
      upper limb, a rare complication of venom snakebite. Administration of antivenom
      and fasciotomy were needed to resolve the acute episode permitting a positive
      outcome. On the basis of literature review and our experience we hypothesize an
      algorithm for the treatment of these patients.

PMID- 22978058
TI  - Unusual form of cutaneous infiltration by cancer.
AB  - Breast cancer is the most common visceral neoplasm which metastatizes in skin.
      Skin infiltration by breast cancer may appear as various types of
      neoplastic/inflammatory lesions, including plaques, pigskin-like areas, scirrhous
      morphea-like lesions, nodules, zosteriform lesions, and papulovescicles. An
      unusual form of cutaneous infiltration involving a mammary region bearing a post
      mastectomy surgical skin scar is herein described: interestingly, such a
      cutaneous cancer involvement could not be included in the above classification,
      because it merely consisted of red-purple areas dealing with small
      telangiectasias, without any sign of inflammation.

PMID- 22978059
TI  - Incidental diagnosis of thoracic ganglioneuroblastoma in a 3-year-old female with
      wheezing.
AB  - Ganglioneuroblastoma (GNB) is a cancer of the peripheral sympathetic nervous
      system and represents the 30% of cases of Neuroblastoma. When originates from
      thoracic ganglia it may appear very late, with severe symptoms like respiratory
      distress or neurological dysfunctions. We present an incidental diagnosis of
      thoracic GNB, discovered by a chest radiography during a recurrent wheezing
      unresponsive to bronchodilators. The early diagnosis allowed a precocious
      treatment probably improving the outcome.

PMID- 22978060
TI  - Sulfonylurea-responsive neonatal diabetes mellitus diagnosed through molecular
      genetics in two children and in one adult after a long period of insulin
      treatment.
AB  - A permanent neonatal diabetes mellitus has finally been diagnosed through
      molecular genetics in two children and one adult after 9 to 35 years of
      uninterrupted insulin treatment. These patients developed diabetes before 6
      months of age and were autoantibody negative. In one boy, a mutation in the
      KCNJ11 gene was identified at 9 years of age. In the other two patients (daughter
      and father, 12.6 and 25 years old respectively) the new gene variant
      (ABCC8/L213P) was found. Switching from insulin to sulfonylurea treatment leads
      to the definitive discontinuance of insulin therapy, improving metabolic control
      as well as the amelioration of the associated neurodevelopmental disabilities in
      the young girl in which an intermediate Development Delay, Epilepsy, Neonatal
      Diabetes syndrome was diagnosed.

PMID- 22978061
TI  - Collatamp sponges in the management of open fractures.
AB  - Open fractures are at high risk of infection and the prompt treatment of these
      injuries is critical to the success and is crucial to reduce the rate of
      complications. The basic steps of treatment include the immediate administration
      of systemic antibiotics, early surgical stabilization of the fracture associated
      with copious irrigation and radical debridement of the site of exposure, and when
      possible adequate soft tissue coverage. The systemic antibiotic therapy
      significantly improves the prognosis and reduces the occurrence of complications.
      However, in order to ensure adequate and sustained local concentration of
      antibiotic agent, high doses and for a long time are necessary. This increases
      the risk of side effects and bacterial resistance. The introduction of the
      antibiotic-loaded collagen sponges offers the advantages of a high local
      concentrations of antibiotic carrier delivering system with reduced systemic drug
      diffusion (less risk of side effects and resistance rate). Sponges are also
      biodegradable and fully resorbable and do not require additional surgery for
      their removal.

PMID- 22978062
TI  - Biases in bone metabolism studies.
AB  - An increase in life expectancy, contracted HIV infections in the elderly,
      comorbidity, and a discrepancy between real and biological age make BMD loss an
      unavoidable phenomenon in each patient. Both HIV and antiretrovirals amplify the
      age effect on BMD. Among N(n)RTIs, the effect oftenofovir on BMD seems to exceed
      the effect of other antiretrovirals, but we can find studies which confirm this
      observation, and other studies which doubt the conclusions and/or minimize the
      implications. This disagreement exists because there are a number of biases in
      all these studies that, unfortunately, compromise the conclusions. In the same
      analyses are men and women, different BMIs, different ages, different times of
      HIV infection before entering the trial, resulting in different biological ages,
      and especially different baseline BMD. All these biases together create a pool
      that is not homogeneous, having many variables, which complicates the correct
      interpretation of the results, especially in comparative studies between two
      pools. BMD in the studies is expressed as percentage loss during the follow-up,
      and not as the variation of absolute values of BMD: this feature may be deceptive
      regarding the real loss of BMD. Another bias is the approximate use, when
      defining BMD loss, of T-score even in non-menopausal women and in men younger
      than 50. Finally, another bias is the use of a different DXA machine to determine
      BMD. Prospective studies with a longer follow-up and without all these biases are
      urgently needed.

PMID- 22978063
TI  - Tumor necrosis factors blocking agents: analogies and differences.
AB  - Five anti-TNF agents, infliximab, adalimumab, etanercept, golimumab and
      certolizumab pegol are approved worldwide for the treatment of RA. Anti-TNF
      agents, bind to and neutralize soluble TNF-alpha, but exert different effects on
      transmembrane TNF-alpha-expressing cells (TNF-alpha-producing cells). Differences
      on affinity and avidity for soluble and transmembrane TNF-alpha were showed.
      Different activity on cells apoptosis, complement-dependent cytotoxicity (CDC)
      antibody dependent cell-mediated cytotoxicity (ACDC) were described. Some
      dramatic changes in gene expression were seen with all the anti-TNFs. Reviewing
      the biology of transmembrane TNF-alpha and its interaction with anti-TNF agents
      will contribute to understanding the bases of differential clinical efficacy of
      these promising treatment modalities.

PMID- 22978064
TI  - Bowen's disease in a renal transplant recipient treated with a single application
      of topical imiquimod: severe adverse skin reaction with favourable clinical
      outcome.

PMID- 22978065
TI  - [Current status and therapeutic strategy for pancreatic neuroendocrine tumors in
      Japan].

PMID- 22978066
TI  - Ten-year survival of curability B gastric cancer patients treated by tegafur
      uracil as postoperative adjuvant chemotherapy in a common public hospital:
      univariate and multivariate analyses.
AB  - PURPOSE: The prognosis of gastric cancer patients undergoing curability B surgery
      was retrospectively examined to determine the effectiveness of the administration
      of oral anti-cancer drugs as postoperative adjuvant chemotherapy. METHODS: This
      study was based on the outcomes of 86 potentially curative patients who had
      undergone curability B resection of gastric cancer with or without the subsequent
      administration of oral 5-fluorouracil analogue. There were 21 patients who
      underwent surgery alone with no oral anti-cancer agents (group A) and 65 patients
      who were treated postoperatively, mainly with UFT (Tegafur and uracil; group B).
      This study compared the ten-year survival times of these two groups using
      univariate and multivariate analyses. RESULTS: The amount of UFT in group B was
      354.2 +/- 122.0 mg and the administration period was 11.7 +/- 7.2 months. The
      backgrounds showed significantly more older patients in group A compared than
      group B (P = 0.0002). A univariate analysis showed the ten-year survival rate in
      group B to be higher than group A (P = 0.0079). A multivariate analysis showed
      that the postoperative administration of UFT was an independent factor associated
      with prolongation of survival times as well as the extent of lymph nodes
      metastasis and pathological stage (P = 0.0096). CONCLUSION: This study provided
      conventional evidence that postoperative administration of oral 5-fluorouracil
      analogue is associated with better long-term prognoses in patients undergoing
      curability B resection for gastric carcinoma.

PMID- 22978067
TI  - [A successful case of living donor liver transplantation performed in 7 hours for
      sub acute fulminant hepatitis].
AB  - Living donor liver transplantation (LDLT) is the ultimate cure for fulminant
      hepatitis. Successful outcomes rely on the precise evaluation of the
      reversibility of hepatic encephalopathy, and a swift execution of necessary
      examination of both the donor and the recipient. The case was a 63-years old
      woman, presented with fever and loss of appetite. She was hospitalized for acute
      hepatitis and treated at a nearby hospital. She was transferred to the tertiary
      hospital for the acute deterioration of her liver function on the 7th day after
      the emergence of the initial symptoms. On the 10th day, she showed Grade 2
      encephalopathy and underwent plasma exchange. She was transported to our hospital
      for possible LDLT on the 11th day. CT scan on arrival showed severe atrophy of
      her liver and no definite brain edema despite acutely deteriorating
      encephalopathy (Grade 3). LDLT was launched after 7 hours from her transport. She
      was discharged from the intensive care unit on the 6th day and was discharged
      without severe complications on 42th day after the LDLT.

PMID- 22978068
TI  - Breaking up is hard to do: psychological entrapment and women's commitment to
      violent dating relationships.
AB  - Psychological entrapment occurs when people continue investing in unfavorable
      situations after already devoting too much to lose. We predicted that women who
      already invested more time and resources into their relationships would exert
      effort to improve their relationships following partner violence. In turn, these
      efforts were expected to increase women's subjective investment in, and thus,
      commitment to violent relationships. Undergraduate women (N = 98) in heterosexual
      relationships reported on partner violence and relationship duration at Time 1
      and relationship sacrifices, subjective investment, and commitment at Times 1 and
      2. As expected, women with violent partners who were in longer term relationships
      sacrificed more 6 weeks later. Unexpectedly, in multivariate analyses, Time 2
      sacrifices were not significantly associated with Time 2 subjective investment,
      although subjective investment was positively associated with concurrent
      commitment. These results provide preliminary evidence for women's entrapment in
      violent relationships.

PMID- 22978069
TI  - Risk estimations of the conjunction of victim and crime event characteristics on
      the lethal outcome of sexual assaults.
AB  - This study examines what factors may distinguish injury from death in sexual
      crimes. We suggest that victim characteristics may work in conjunction with the
      crime context to enhance or reduce a fatal outcome once a sexual assault is
      underway. Based on a sample of 201 sex offenders who either physically injured or
      killed their victim, we calculate risk estimations of lethal and injurious
      outcomes for various conjunctions of victim characteristics and contextual
      aspects of the crime event. One of the most interesting findings is the apparent
      protective effects of a victim's criminogenic environment, which consistently
      appears to decrease the probability of a fatal outcome.

PMID- 22978070
TI  - Military sexual trauma during deployment to Iraq and Afghanistan: prevalence,
      readjustment, and gender differences.
AB  - This study examines military sexual trauma (MST) in men and women deployed in the
      wars in Iraq and Afghanistan. A diverse sample of 470 (408 men and 62 women)
      completed anonymous self-report questionnaires. Seventy-seven reported MST: 51
      (12.5%) men and 26 (42%) women. MST was significantly related to symptoms and
      readjustment and most strongly with intimacy problems. Of those with MST, 73%
      also reported exposure to war-related stressors. Gender differences revealed that
      women reported a higher prevalence of MST, but men were more likely to endorse
      MST with multiple war-related stressors. However, no gender differences were
      found on reports of symptoms, posttraumatic stress disorder (PTSD), or
      readjustment. Implications of these results are discussed.

PMID- 22978071
TI  - Mock juror perception of sexual assault nurse examiner testimony.
AB  - The perception of a sexual assault nurse examiner's (SANE) testimony in a
      criminal rape trial was investigated. Men and women undergraduates (N = 138) read
      a fictional criminal trial summary of a rape case in which medical testimony from
      a SANE or a registered nurse (RN) was presented, or no medical testimony was
      presented. Results indicated that mock jurors were more likely to render guilty
      verdicts when a SANE testified than when an RN testified, and this relationship
      was fully mediated by perceived credibility of the nurse as well as provictim
      perceptions. Results are discussed in terms of the impact of SANE involvement in
      legal proceedings.

PMID- 22978072
TI  - The impact of parental trauma exposure on community violence exposed adolescents.
AB  - Previous research has documented an association between adolescent community
      violence (CV) exposure and poor psychological functioning. The purpose of this
      study was to delineate the relations of adolescent CV, parent trauma exposure
      (PTE), and adolescent internalizing and externalizing symptomatology while
      controlling for adolescent-reported home violence and parental self-reported
      posttraumatic stress disorder (PTSD). Participants consisted of 101 pairs of
      junior high school and high school students and their parents or caretakers.
      Adolescents completed measures to assess their history of violence exposure in
      the community and home setting and current internalizing symptoms. Parents or
      caretakers completed a demographic questionnaire, a measure assessing their
      trauma exposure and related symptomatology, and a measure of child externalizing
      symptoms. Hierarchical regression analyses were conducted; results indicated that
      after controlling for demographic variables, home violence exposure, and parental
      PTSD symptoms, PTE emerged as a moderator variable in the relationship between CV
      and adolescent-rated internalizing symptoms but not in the association between
      adolescent CV and externalizing symptoms.

PMID- 22978074
TI  - Mexican immigrant survivors of intimate partner violence: conceptualization and
      descriptions of abuse.
AB  - This phenomenological qualitative study examines intimate partner violence (IPV)
      experienced by a sample of 29 Mexican immigrant women residing in New York and
      St. Louis. The findings reveal important insights about culturally specific abuse
      tactics employed by batterers and the forms of abuse that are experienced as most
      hurtful to the survivors. Ten different abusive tactics emerged: verbal,
      economic, physical, sexual, and extended family abuse, social isolation, physical
      abuse of children, stalking and monitoring, stolen bride, and sex trafficking.
      Cultural values and expectations appear to be inextricably linked to how the
      participants characterized the severity of each of the abusive tactics as
      evidenced by which abusive behaviors the participants found most hurtful. The
      findings will help service providers have a better understanding of the role
      cultural context plays in the IPV experiences of Mexican immigrant women.

PMID- 22978073
TI  - Violence victimization of young men in heterosexual relationships: does alcohol
      outlet density influence outcomes?
AB  - This study examined whether alcohol outlet density is associated with male
      physical and sexual victimization by a female partner. Data were from the
      National Longitudinal Study of Adolescent Health (Add Health). A total of 3,179
      young adult men identified a current heterosexual relationship and had complete
      intimate partner violence (IPV) victimization data. Almost 16% of this sample
      reported being the victim of physical only IPV in their relationship over the
      previous 12 months; an additional 6.4% were victims of sexual only or sexual and
      physical IPV. Multivariate analyses indicated high alcohol outlet density was
      associated with greater odds of experiencing physical IPV only (odds ratio [OR] =
      2.07). Heavy drinkers experienced increased odds of physical and sexual IPV
      victimization. Alcohol outlet density should be addressed in prevention efforts.

PMID- 22978075
TI  - Bystander perceptions: implications for university sexual assault prevention
      programs.
AB  - The college party environment comprises a risk factor for unwanted sexual
      activity but may also provide a safety net, given the presence of bystanders who
      can potentially intervene in risky situations. Sexual assault prevention programs
      are increasingly incorporating bystander education into their designs. This
      article presents findings intended to inform these programs. Qualitative data
      from single-sex focus groups about typical college party behavior was analyzed
      for common themes. Analysis of these themes suggests that although some sexual
      behavior is visible at college parties, most sexual behavior is assumed to occur
      behind closed doors. In addition, intervention and prevention methods may vary by
      gender. Multiple factors appear to promote or dissuade bystander intervention in
      college party situations.

PMID- 22978076
TI  - The relationship between dating violence and suicidal behaviors in a national
      sample of adolescents.
AB  - Relationship violence is a common problem faced by adolescents in the United
      States. In general, adolescents are at higher risk for relationship victimization
      than adults (Silverman, Raj, Mucci, & Hathaway, 2001), and females between the
      ages of 16 and 24 years are at the highest risk of relationship victimization
      (Rennison, 2001). This study uses data from the 2007 Youth Risk Behavior
      Surveillance (YRBSS) System (or referred to as Youth Risk Behavior Survey [YRBS];
      N = 11,781) of adolescents between the ages of 14 and 17 years to estimate two
      logistic regression models on the association between relationship violence and
      suicidal behaviors controlling for variables such as sexual assault and drug use.
      The findings indicated that victimized adolescents are at higher risk for
      planning and/or attempting suicide compared to nonvictimized adolescents.
      Implications for research and practice are explored.

PMID- 22978077
TI  - Prevalence and characteristics of sexual violence in the Netherlands, the risk of
      revictimization and pregnancy: results from a national population survey.
AB  - Prevalence figures on sexual violence among a representative sample of both men
      and women were not yet available for the Netherlands. The aim of this study,
      therefore, was to investigate the prevalence of sexual violence in the
      Netherlands and to add these figures to the international body of knowledge.
      Experiences of sexual violence during lifetime, before the age of 16 and in the
      year before the start of the study were measured. In addition, types of sexual
      violence were examined, as were the characteristics of the perpetrators. Lastly,
      revictimization and pregnancy as a result of rape experiences among the victims
      were investigated. Data were generated from a population survey on sexual health.
      The sample consisted of more than 6,000 men and women between the age of 15 and
      70 years old. Prevalence rates as high as 21% for men and 56% for women were
      found. Fifty percent of the female victims and 30% of the male victims of child
      sexual abuse had experienced adult victimization. Of the female rape victims, 7%
      became pregnant as a consequence of rape. In the Netherlands, as elsewhere, the
      prevention of sexual violence should be prioritized.

PMID- 22978078
TI  - Meeting the training needs of those who meet the needs of victims: assessing
      service providers.
AB  - Despite growing awareness of crime victims' needs for support and services, few
      studies have examined the training needs of those who provide such services. This
      research presents the results of statewide needs assessment of victims services
      providers (VSPs) conducted in preparation for designing a state victim assistance
      training academy. Respondents were asked to indicate their needs for training on
      various topics pertaining to victims services. Results indicate that extent of
      formal education and years of experience in the field are the primary
      determinants of reported needs for training. Respondents with less formal
      education and less experience in the field, regardless of the nature of their
      organizational position (client services vs. management), report greater needs
      for training. Implications for designing training programs for VSPs are
      discussed.

PMID- 22978079
TI  - Psychiatric consultation after kidney transplantation: a 10-year single-center
      study including outpatients in Japan.
AB  - BACKGROUND: The aim of this study was to elucidate the clinical characteristics
      and frequency of psychiatric consultation in a routine clinical setting after
      kidney transplantation. METHODS: Subjects were 1,139 consecutive recipients who
      received kidney transplantation at our hospital between January 1997 and
      September 2006. The hospital patient database was searched to determine whether
      these recipients received psychiatric consultation after their transplantation
      during this period. RESULTS: Among 1,139 recipients, 118 (10%) received
      psychiatric consultation after their transplantation. There were significantly
      more women among these recipients (p = 0.036). Many of the recipients had
      received psychiatric consultation before transplantation (p < 0.0001) and had
      received dialysis for a long time (p = 0.018). There were three main psychiatric
      diagnoses according to ICD-10 diagnostic criteria in these 118 recipients: 42
      (36%) had neurotic, stress-related, and somatoform disorders (F4); 35 (30%) had
      organic, including symptomatic, mental disorders (F0); and 27 (23%) had mood
      (affective) disorders (F3). The median length of time between kidney
      transplantation and initial psychiatric consultation was 57 days (interquartile
      range: 10-650 days). The lengths were 7 days (6-17 days) for F0, 75 days (18-650
      days) for F4, 243 days (35-1,004 days) for F3, and 253 days (10-1,393 days) for
      other diagnostic groups. Significant differences were observed among these four
      groups (Jonckheere-Terpstra test, p < 0.001). CONCLUSION: Our results show that
      appropriate psychiatric intervention is necessary not only in early stages after
      kidney transplantation but also over the long term.

PMID- 22978080
TI  - Is the cognitive-behavioral therapy an effective intervention to prevent the
      postnatal depression? A critical review.
AB  - OBJECTIVE: The aim of this article is to review and discuss the efficacy of the
      Cognitive-Behavioral Therapy (CBT), in the prevention of postnatal depression
      (PD) in pregnant women at risk. METHOD: PubMed, Medline, PsychInfo, Embase, and
      the Cochrane Library databases were searched from February 1991 to February 2011.
      RESULTS: Eight Randomized Controlled Trials (RCT) on the prevention of PD with
      the CBT were selected and their data were analyzed. The literature analyzed
      recommends that depression in pregnancy requires an efficient management to
      provide mother's symptoms relief as well as to prevent the PD. While several
      studies demonstrated the efficacy of the CBT in the treatment of PD, the efficacy
      of the CBT in preventing PD in pregnant women at risk has been investigated only
      by a few studies, presenting a number of methodological flaws. CONCLUSIONS:
      Better designed RCT are needed to support the efficacy of such psychotherapeutic
      preventive strategy in women at risk for PD.

PMID- 22978081
TI  - Depression, anxiety, body image, sexual functioning, and dyadic adjustment
      associated with dialysis type in chronic renal failure.
AB  - OBJECTIVE: Depression is the most widely studied complication in dialysis
      patients. In patients with chronic renal failure, changes in body image are
      considered to be associated with invasive treatment interventions. In addition,
      sexual problems are common in dialysis patients. In this study, hemodialysis and
      peritoneal dialysis patients are investigated for depression, anxiety, body
      image, sexual satisfaction, and dyadic adjustment. METHODS: Hemodialysis patients
      (n = 36), peritoneal dialysis patients (n = 54), and healthy controls (n = 30)
      were included in the study. All the subjects were assessed with Structured
      Clinical Interview for DSM-IV, Body Image Scale, Beck Depression Inventory, Beck
      Anxiety Scale, Golombok-Rust Inventory for Sexual Satisfaction, and Dyadic
      Adjustment Scale. RESULTS: Depression (20.64 +/- 15.20) and anxiety levels (14.72
      +/- 12.36) were significantly higher in hemodialysis group compared to peritoneal
      dialysis (13.54 +/- 12.51; 12.74 +/- 11.21) and control groups (7.17 +/- 5.58;
      9.86 +/- 9.19). In peritoneal dialysis group, as depression and anxiety levels
      increased, body image was disturbed and sexual satisfaction decreased. In
      peritoneal dialysis group, body image (86.98 +/- 23.63) was better than
      hemodialysis group (101.58 +/- 26.51) and was not different from the control
      group (83.67 +/- 22.11). In hemodialysis group, as depression and anxiety levels
      increased, body image was disturbed. In both groups, long-term dialysis disturbed
      body image. CONCLUSION: Patients should be informed about the impacts of
      dialysis. Clinicians may wish to monitor dialysis-users for anxiety, depression,
      dyadic adjustment, and body image difficulties at follow-up appointments.
      Interventions that target intimate partner interventions, appearance-related
      beliefs, and anxiety depression may be of benefit to this population.

PMID- 22978082
TI  - The relationship between postpartum depression and breastfeeding.
AB  - INTRODUCTION: The purpose was to investigate the possible correlation or
      predictive relationship between breastfeeding and Postpartum Depression (PPD).
      METHOD: We conducted a prospective study in which 137 Arab women were assessed
      during pregnancy and postpartum. Current breastfeeding was correlated with
      postpartum outcomes (EPDS and MINI), employment, and use of formula at 2 and 4
      months postpartum, as well as with other variables. RESULTS: Women who were
      breastfeeding at 2 and 4 months had lower scores on EPDS (p < 0.0037 andp <
      0.0001, respectively) and were less likely to be diagnosed with PPD at 4 months
      (p < 0.0025). Higher scores on EPDS and diagnosis of PPD at 2 months were
      predictive of lower rates of breastfeeding at 4 months (p < 0.0001 and p < 0.005,
      respectively). Women who were employed and using formula at 2 months were less
      likely to breastfeed at 4 months (p < 0.0001). Breastfeeding women at 2 months
      had lower scores on EPDS (p < 0.003) and were less likely to be diagnosed with
      PPD (p <0.05) at 4 months. DISCUSSION: The results indicate that women who
      breastfeed their infants reduced their risk of developing PPD, with effects being
      maintained over the first 4 months postpartum. PPD may also decrease the rate of
      breastfeeding, suggesting a reciprocal relationship between these variables.

PMID- 22978083
TI  - Adjunctive treatment with gabapentin in bipolar patients during acute mania.
AB  - OBJECTIVE: In this clinical trial, we studied the effects of adjunctive treatment
      with gabapentin in controlling the symptoms of acute mania in patients admitted
      with bipolar disorder. METHOD: Sixty patients with bipolar disorder (30 men and
      30 women) admitted in the acute phase of mania were categorized as case and
      control groups, each holding 30 patients. Both groups were treated with lithium
      for 6 weeks and the case group received an adjunctive treatment with 900 mg
      gabapentin simultaneously. All patients were evaluated at the beginning and the
      end of the trial using Young's Mania Rating Scale (YMRS), and two groups were
      compared for improvement in acute symptoms. FINDINGS: The final score of YMRS was
      significantly improved in the case group compared to the control group (p =
      0.00). The improvement of YMRS score was not significantly different between men
      and women and between different age groups. CONCLUSION: Adjunctive treatment with
      gabapentin is effective for controlling symptoms of acute mania.

PMID- 22978084
TI  - The abuse of prescription medications and employment history.
AB  - OBJECTIVE: The relationship between prescription medication abuse and employment
      history is rarely studied and is the focus of the present study. METHOD: Using a
      cross-sectional consecutive sample of 325 internal medicine outpatients and a
      self-report survey methodology, we examined prescription medication abuse ("Have
      you ever intentionally, or on purpose, abused prescription medications?") and
      four employment variables. RESULTS: We found statistically significant
      relationships between the abuse of prescription medications and all four
      employment variables--i.e., number of different jobs held since age 18 (5.05 in
      nonabusers versus 7.81 in past abusers), estimated percentage of time employed
      since age 18 (79.0% in nonabusers versus 63.3% in past abusers), being paid
      "under the table" (24.9% in nonabusers versus 77.4% in past abusers), and being
      fired (37.2% in non-abusers versus 64.5% in past abusers)--all indicating less
      employment viability in participants with past histories of prescription
      medication abuse. CONCLUSIONS: The abuse of prescription medications is
      associated with impaired functionality in the work arena.

PMID- 22978085
TI  - Religion and smoking: a review of recent literature.
AB  - Tobacco smoking and exposure to secondhand smoke are a major threat to human
      health worldwide. The effort to prevent tobacco use should be regarded as an
      important public health strategy. Given the significance of religion and
      spirituality in the daily life of more than 90% of the world's population, the
      relationship of religion and smoking should be seen as a critical research area.
      Religions are many and varied, but most value human well-being highly and so do
      not approve of tobacco use, even though they do not prohibit it entirely. In
      recent years, researchers have shown more interest in the subject of religion and
      health, including drug and tobacco use. Differences of focus and methodology
      notwithstanding, most studies have ascertained a deterrent role for religion as
      regards tobacco use, and several mechanisms have been proposed to explain the
      negative relationship between religion or spirituality and smoking. Many of the
      studies, however, suffer from shortcomings that need to be acknowledged and
      addressed, such as using nonstandard data-gathering tools, lack of a unified
      definition of religion or spirituality, and paucity of research in non-Christian
      and developing countries. Finally, the cross-sectional nature of many of the
      studies makes the meaningful interpretation of findings difficult.

PMID- 22978086
TI  - [Succeeding the humanity spirit of esteemed prof. Yue, Mei-Zhong].

PMID- 22978087
TI  - [The treatment principle and methods for Chinese medicine and pharmacy in
      treating AIDS mainly by qi benefiting method].

PMID- 22978088
TI  - [The thinking way, methods, and results of Chinese medicine syndrome studies on
      AIDS].

PMID- 22978090
TI  - [Consensus on the diagnosis and treatment of peptic ulcer by integrative medicine
      (Tianjin 2011)].

PMID- 22978089
TI  - [Research and prospect of asymptomatic HIV infection stages].

PMID- 22978091
TI  - [Consensus on the diagnosis and treatment of chronic gastritis by integrative
      medicine (Tianjin 2011)].

PMID- 22978092
TI  - [Effects of fuzheng paidu tablet on tumor necrosis factor-alpha and neopterin of
      thirty-two asymptomatic HIV carriers].
AB  - OBJECTIVE: To explore the effects of Fuzheng Paidu Tablet (FPT) on serum levels
      of tumor necrosis factor-alpha (TNF-alpha) and neopterin (NPI) in patients with
      asymptomatic human immunodeficiency virus (HIV) carriers. METHODS: Using flow
      cytometry detection technology, CD T lymphocyte in anticoagulant blood sample of
      32 asymptomatic HIV infection patients who were taking FPT for 6 months was
      detected and compared with before treatment. The serum levels of TNF-alpha and
      NPI were determined using ELISA method and compared with 22 healthy volunteers.
      RESULTS: After 6 months of treatment by FPT, the CD4+ T lymphocyte of
      asymptomatic HIV carriers increased from (368.63 +/- 111.54)/mm3 to (412.72 +/-
      159.63)/mm3. Before treatment the serum levels of TNF-alpha [(20.05 +/- 13.08)
      nmol/L] and NPI [(9.55 +/- 2.52) nmol/L] were obviously higher than those of the
      healthy volunteers [(12.20 +/- 4.07) nmol/L and (5.91 +/- 1.43) nmol/L] (P <
      0.05). After 6 months of treatment by FPT, they were lower after treatment than
      before treatment (P < 0.05). But there was no statistical difference in the serum
      TNF-alpha level [(11.06 +/- 4.71) nmol/L] when compared with the healthy
      volunteers group (P > 0.05). But the serum NPI level [(8.08 +/- 2.13) nmol/L] was
      still higher than that of the healthy volunteers group (P < 0.05). CONCLUSIONS:
      One of the pathological factors for asymptomatic HIV infection is abnormal immune
      activation represented by increased serum levels of TNF-alpha and NPI. FPT could
      lower the serum levels of TNF-alpha and NPI in asymptomatic HIV infection
      patients, which was one of its possible mechanisms for its efficacy.

PMID- 22978093
TI  - [Study on the regional features of Chinese medicine etiology and pathogenesis of
      AIDS].
AB  - OBJECTIVE: To analyze the differences in the Chinese medicine (CM) etiology and
      pathogenesis of AIDS. METHODS: A cross-sectional investigation study of AIDS
      patients and non-infected people was carried out in Henan, Guangdong and Xinjiang
      provinces respectively by questionnaire of clinical epidemiology and analyzed
      with frequencies of symptoms and signs combined with syndrome factors. The
      distribution differences of syndrome factors in the 3 provinces were compared.
      RESULTS: Totally 321 cases were investigated in the 3 provinces. As for the
      syndrome factors of AIDS, qi deficiency, blood deficiency, yin deficiency, yang
      deficiency, dampness evil, phlegm, qi stagnation, essence deficiency, and so on
      were dominated in the 3 provinces, but with their own features. For example, the
      scores of dampness evil were higher in Guangdong Province. Yin deficiency was
      dominated in Xinjiang Province. The scores of Henan Province were generally
      higher. As for the location of syndrome factors, Shen, Fei, Pi, and Gan were
      dominated in the 3 provinces. The score of Pi was the highest in Guangdong
      Province, while the score of Shen was the highest in Henan and Xinjiang
      provinces. CONCLUSIONS: AIDS has regional features in the nature and the syndrome
      factors of location in different provinces. It is necessary to take into
      consideration the regional factors when analyzing the pathogenesis of AIDS.

PMID- 22978094
TI  - [Analyzing Chinese medicine syndromes of hematotoxicity reaction induced by
      highly active antiretroviral therapy].
AB  - OBJECTIVE: To investigate the main features of Chinese medicine (CM) syndromes
      and differences of hematotoxicity reaction induced by highly active
      antiretroviral therapy. METHODS: The information of CM four diagnostic methods
      was collected by cross-sectional study. Their syndrome features were summed up
      and their differences were analyzed. RESULTS: Of the 216 patients, the main
      syndromes were qi-blood deficiency syndrome (142 cases, accounting for 65.7%) and
      Pi-Shen yang deficiency syndrome (74 cases, accounting for 34.3%). The score of
      qi-blood deficiency syndrome was obviously lower than that of Pi-Shen yang
      deficiency syndrome (P < 0.05). The count of CD4+ T cells was higher in qi-blood
      deficiency syndrome than in Pi-Shen yang deficiency syndrome. There was no
      statistical difference in the serum viral load between the two groups (P > 0.05).
      The quality of life was higher in qi-blood deficiency syndrome than in Pi-Shen
      yang deficiency syndrome, but with no statistical difference (P > 0.05).
      CONCLUSIONS: Qi-blood deficiency syndrome and Pi-Shen yang deficiency syndrome
      were main syndromes of hematotoxicity reaction induced by HAART. The pathogenic
      condition of qi-blood deficiency syndrome patients was milder. There was no
      obvious difference in the quality of life, CD4+ T cells, and the viral loads
      between two syndromes.

PMID- 22978095
TI  - [Diagnosis and treatment standard operating procedure of traditional Chinese
      medicine for HIV/AIDS diarrhea by questionnaire building].
AB  - OBJECTIVE: To establish the diagnosis and treatment standard operating procedure
      of Chinese medicine for HIV/AIDS diarrhea and to carry out preliminary
      assessment. METHODS: Under the guidance of Chinese medical theory, domestic and
      foreign literatures correlated to the diagnosis and treatment of HIV/AIDS
      diarrhea by Chinese medicine were summarized. The specialist questionnaire of
      clinical diagnosis and treatment standard operating procedures of Chinese
      medicine for HIV/AIDS diarrhea was designed by focus group discussions, and the
      national specialist questionnaire survey was carried out twice. RESULTS: The
      standard operating procedure of clinical diagnosis, treatment, nursing,and
      therapeutic efficacy assessment of Chinese medicine for HIV/AIDS diarrhea was
      preliminarily established. CONCLUSIONS: In the regulations, the concepts of the
      disease and symptoms and their pathogenesis were defined, and the standardization
      of Chinese medicine diagnosis and treatment was highlighted. Meanwhile,
      emphasized were the features of propaganda and education, follow-ups, consecutive
      diagnosis and treatment outside or inside hospitals.

PMID- 22978096
TI  - [Study of Chinese medicine syndrome patterns in 346 patients with papular
      eruption].
AB  - OBJECTIVE: To study the Chinese medicine (CM) syndrome laws of patients with
      pruritic papular eruption (PPE), thus providing reference for its classification
      and standard diagnosis. METHODS: Using multicenter, prospective trials in 346 PPE
      patients,the correlations between sex, age, infection route, and CD4 levels and
      CM syndrome patterns were analyzed. The syndrome laws correlated with PPE was
      studied from the macroscopic and microscopic aspects. RESULTS: There was no
      statistical difference in sex, age, or CD4 level among various CM syndrome
      patterns. There was statistical difference in the infection route among various
      CM syndrome patterns. Pi-deficiency dampness-accumulation syndrome occurred more
      in patients infected by blood. Wind production induced by heat in blood syndrome
      occurred more in those infected by sexual contact. Blood deficiency wind dryness
      syndrome occurred in those infected by intravenous drug abuse. CONCLUSIONS: Wind
      production induced by heat in blood syndrome, blood deficiency wind dryness
      syndrome, and Pi-deficiency dampness-accumulation syndrome exist in CM syndrome
      types of AIDS. There was statistical difference in different infection routes of
      the distribution of each syndrome type.

PMID- 22978098
TI  - [Effects of Yupei Qisun Sequential Method of Chinese medicine on correlated
      indices of repeated implantation failure patients in the fresh cycle].
AB  - OBJECTIVE: To study the clinical effects of Yupei Qisun Sequential Method (YQSM,
      by Shen supplementing and Pi invigorating) of Chinese medicine on correlated
      indices of repeated implantation failure patients in the fresh cycle. METHODS:
      Sixty patients with more than three failure cycles of in virto fertilization and
      embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI) were
      recruited. They were assigned to the treatment group (treated by IVF/ICSI and
      Chinese medicine) and the control group (treated by IVF/ICSI alone), 30 in each
      group. The total dose of gonadotropin (Gn), the days of controlled ovary
      hyperstimulation (COH), the thickness of endometrium on the day of embryo
      transplantation, the number of retrieved oocytes, the fertilization number, the
      embryo number, the high quality embryo number, the pregnancy rate, and the
      implantation rate were compared. RESULTS: In the treatment group the numbers of
      embryo and high quality embryo were 7.5 +/- 4.9 and 5.1 +/- 3.2 respectively,
      which were both higher than those of the control group with significant
      difference (5.1 +/- 3.2, 3.2 +/- 1.8; P < 0.05). No significant difference
      existed in aspects of the total numbers of Gn, the days of COH, the thickness of
      endometrium on the day of embryo transplantation, the numbers of retrieved
      oocytes, the fertilization number, the pregnancy rate, and the implantation rate
      between the two groups (P > 0.05). CONCLUSION: YQSM combined with COH could
      improve the quantity and the quality of embryos, which was promising to increase
      the accumulative pregnancy rate of RIF patients.

PMID- 22978099
TI  - [Immunoregulation effects of Tiaomian No. 3 for recurrent spontaneous abortion
      caused by shortage of blocking antibodies].
AB  - OBJECTIVE: To study the immunoregulation effects of Tiaomian No. 3 (TM3) for
      recurrent spontaneous abortion (RSA) caused by shortage of blocking antibodies.
      METHODS: Totally 61 patients with RSA caused by shortage of blocking antibodies
      were randomly assigned to the treatment group (31 cases) and the control group
      (30 cases) by lot method. Patients in the treatment group were treated with TM3,
      while those in the control group were treated with active immunotherapy using
      lymphocytes of their spouses. The therapeutic course for all was 3 months.
      Another 10 healthy females in the same age ranges were recruited as the healthy
      control group. The blocking antibodies (Ab1), anti-idiotypic antibodies (Ab2), T
      lymphocyte cell subsets (CD4 and CD8), serum interleukin 10 (IL-10), and
      macrophage colony-stimulating factor (M-CSF) levels were determined before and
      after treatment. RESULTS: (1) After treatment the positive conversion rate of Ab1
      and/or Ab2 was 87.1% (27/31) in the treatment group and 86.7% (26/30) in the
      control group, showing no statistical difference (P > 0.05). (2) In the two
      groups, CD4 decreased and CD8 increased. The CD4/CD8 ratio was in the normal
      level after treatment, showing statistical difference when compared with before
      treatment (P < 0.05). (3) In the two groups, IL-10 and M-CSF levels were higher
      after treatment, showing statistical difference when compared with before
      treatment (P < 0.05). (4) The 1-year conception rate was 58.1% (18/31) in the
      treatment group, significantly higher than that in the control group (46.7%,
      14/30, P < 0.05). CONCLUSIONS: TM3 could promote the positive conversion rate of
      Ab1, promote the production of IL-10 and M-CSF cytokines, thus strengthening the
      protection for fetus by the mother and the normal maintenance for pregnancy. The
      1-year successful pregnancy rate obviously increased in the treatment group.

PMID- 22978100
TI  - [Clinical investigation of Chinese medicine syndromes in two hundred girls of
      advanced puberty].
AB  - OBJECTIVE To analyze the Chinese medicine (CM) syndrome typing features for girls
      with advanced puberty. METHODS: The CM symptoms of girls with advanced puberty in
      the Department of CM, Children's Hospital of Fudan University from March 2008 to
      March 2011 were recruited and statistically analyzed. The CM syndrome typing
      features were summed up. RESULTS: Yin deficiency induced fire hyperactivity
      syndrome (174 cases, accounting for 87.0%) occupied the highest ratio in the main
      syndrome diagnosis, followed by Gan depression transforming into fire syndrome
      (25 cases, accounting for 12.5%) and the endoretention of damp heat syndrome (1
      case, accounting for 0.5%). The mean rank of the 3 syndrome types was sequenced
      from yin deficiency induced fire hyperactivity syndrome (462.87), Gan depression
      transforming into fire syndrome (287.22), and the endoretention of damp heat
      syndrome (146.91). Of them 149 (accounting for 74.5%) girls were diagnosed with
      both yin deficiency induced fire hyperactivity syndrome and Gan depression
      transforming into fire syndrome. Yin deficiency induced fire hyperactivity
      syndrome accompanied with Gan depression transforming into fire syndrome was the
      most often seen (88 cases, accounting for 44.0%), followed by Gan depression
      transforming into fire syndrome accompanied with yin deficiency induced fire
      hyperactivity syndrome (46 cases, accounting for 23.0%). CONCLUSIONS: Yin
      deficiency induced fire hyperactivity syndrome and Gan depression transforming
      into fire syndrome were the leading patterns of CM syndrome typing for girls with
      advanced puberty. It must not neglect their combinations in clinical syndrome
      typing.

PMID- 22978101
TI  - [Clinical study of integrative treatment for ninety-one elderly patients with
      advanced non-small cell lung cancer].
AB  - OBJECTIVE: To observe the effects of integrative therapy on elderly patients with
      advanced nonsmall cell lung cancer (NSCLC), thus providing clinical evidence for
      further studies. METHODS: Totally 91 elderly patients with advanced NSCLC were
      randomly assigned to three groups, i.e., the Chinese medicine (CM) group (Group
      I, 31 cases), the chemotherapy group (Group II, 30 cases), and the CM and
      chemotherapy combination group (Group III, 30 cases). Oral administration of CM
      decoction and intravenous dripping of Chinese patent medicine were given to
      patients in Group I. Patients in Group II received chemotherapeutic protocol
      alone. Patients in Group III received chemotherapeutic protocol while taking CM
      decoction. Twenty-eight days were taken as one therapeutic course, and two
      courses in total. They were observed for two treatment courses by taking Symptoms
      Scale of CM to Primary Lung Cancer, bone marrow depression score, and progression
      free survival (PFS) as therapeutic efficacy indices. Meanwhile, the Cox's
      proportional hazards regression model was established to analyze the favorable
      factors and risk factors that influenced patients' PFS. RESULTS: The CM symptom
      integral of Group I and Group III was superior to that before treatment, showing
      statistical difference (P < 0.01). The occurrence of bone marrow depression in
      Group III was lower than that in Group II. The degree of bone marrow depression
      was also milder in Group III than in Group II, but there was no statistical
      difference in inter-group comparison (P = 0.097, P = 0.299). The PFS was 202 days
      in Group III, 168 days in Group I, and 129 days in Group II. It was better in
      Group III than in Group II (P = 0.0157). The Cox regression analysis showed that
      positive factors to longer PFS included CM + chemotherapy, no surgical
      management, and PS = 1. CONCLUSIONS: CM therapy could improve the symptoms of
      elderly patients with advanced NSCLC. It might extend the PFS of the elderly
      patients by CM therapy combined with chemotherapy.

PMID- 22978102
TI  - [Clinical study of Qianggu granule and diacerein capsule in treating knee
      osteoarthritis].
AB  - OBJECTIVE: To observe the therapeutic efficacy of Qianggu Granule (QGG),
      Diacerein Capsule (DC), and QGG + DC in treating knee osteoarthritis (KOA,
      belonging to Gan-Shen insufficiency induced vein stasis syndrome), and to explore
      the clinical advantages of QGG + DC. METHODS: Ninety patients in line with the
      diagnosis standard were randomly assigned to three groups, i. e., the QGG group
      (30 case, treated by QGG), the Western medicine treatment group (30 case, treated
      by DC), and the combination therapy group (30 case, treated by QGG +DC). Then the
      patients' symptoms and signs were scored. Meanwhile, C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), tumor necrosis factor alpha (TNF-alpha),
      comprehensive efficacy, and adverse reactions, etc. were assessed. RESULTS: The
      ache could be obviously alleviated, the patients' joint function could be
      improved, and their quality of daily activities could be elevated in all the 3
      groups. There was statistical difference in the symptoms and signs scores, CRP,
      ESR, and TNF-alpha before and after treatment (P < 0.05). Better effects were
      obtained in the combination therapy group (P < 0.05). As for the comprehensive
      efficacy, it was better in the QGG + DC group than in the QGG group and the DC
      group, showing statistical difference (P < 0.01). CONCLUSIONS: The comprehensive
      therapeutic efficacy of applying QGG + DC in treating KOA (belonging to Gan-Shen
      insufficiency induced vein stasis syndrome) was superior to using QGG or DC
      alone. Besides, no obvious adverse reaction occurred.

PMID- 22978103
TI  - [Effects of di'ao xinxuekang soft capsule on lipid peroxidation and the
      endothelial function in patients with coronary heart disease].
AB  - OBJECTIVE: To observe the effects of Di' ao Xinxuekang Soft Capsule (DK) on the
      plasma levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide
      (NO), and endothelin (ET) in patients with coronary heart disease (CHD), and to
      study its underlying mechanisms. METHODS: Totally 100 patients with CHD confirmed
      by coronary angiography were randomly assigned to two groups, the control group
      (60 cases) and the DK treatment group (40 cases). Patients in the control group
      received conventional therapy, while those in the DK treatment group received DK
      additionally. The therapeutic course for all was 3 months. The plasma levels of
      SOD, MDA, ET, and NO were determined pre-treatment, 4, 8, and 12 weeks after
      treatment. RESULTS: Compared with before treatment, the serum levels of SOD and
      NO increased and the levels of MDA and ET decreased at each time point. Besides,
      better effects were obtained in the DK treatment group (P < 0.05). CONCLUSION: DK
      possibly played a role in inhibiting lipid peroxidation and improving the
      endothelial dysfunction.

PMID- 22978104
TI  - [Effects of transcutaneous electrical acupoint stimulation combined general
      anesthesia in controlled hypotension at different levels on the liver blood flow
      ].
AB  - OBJECTIVE To observe the changes of the liver blood flow in controlled
      hypotension by transcutaneous electrical acupoint stimulation (TEAS) combined
      general anesthesia, thus clarifying the mechanism of liver protection effect in
      acupuncture anesthesia combined with drugs. METHODS: Forty-two male beagles were
      randomly divided into seven groups, i.e. , the general anesthesia group, the 50%
      control group, the 50% experiment group, the 40% control group, the 40%
      experiment group, the 30% control group, and the 30% experiment group, 6 in each
      group. Beagles in the latter six groups were administered with isoflurane
      inhalation and intravenous dripping of sodium nitroprusside (SNP) for controlled
      hypotension. The mean arterial pressure (MAP) was lowered to 50%, 40%, and 30%
      basic MAP and lasted for 60 min. Beagles in the general anesthesia group was not
      treated with controlled hypotension. In the experiment groups, TEAS was applied
      to bilateral Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), and Quchi (LI11) at
      2/100 Hz with the stimulation strength of 4 +/- 1 mA. The TEAS started from the
      stability of physiological conditions to 60 min after maintaining the target MAP.
      The changes of blood flow of the liver tissue surface at corresponding time
      points were monitored by laser Doppler blood flow meter. RESULTS: Between the
      beginning of hypotension and the maintaining stage of target low blood pressure,
      the liver blood flow of the 50% control group was significantly lower than the
      level of the general anesthesia group and the basic level at corresponding time
      points (P < 0.05). It was significantly reduced in the 50% experiment group only
      at 30-60 min of maintenance. Besides, in the early period of maintenance (10-30
      min), it was significantly higher in the 50% experiment group than in the 50%
      control group at the same time points (P < 0.05). In this stage, there was no
      obvious increase in the liver blood flow in the 40% and 30% experiment groups. In
      the recovery phase of blood pressure (20-30 min), the liver blood flow of the 40%
      experiment group had been restored to the level of the 40% control group and the
      basic level, while it had not been restored in the general anesthesia group. In
      this stage, the similar changing tendency of the liver blood flow occurred in the
      50% and 30% experiment groups and the 50% and 30% control groups. CONCLUSIONS:
      Line to a high level of controlled hypotension (50%), TEAS liver protective
      effect was obviously embodied in the early step-down phase and the maintenance
      phase. Line-induced hypotension to a lower level (40%), TEAS liver protective
      effect was obviously embodied in the recovery phase.

PMID- 22978105
TI  - [Effects of Bushen Zhuangjin Decoction containing serum on the apoptosis of
      chondrocytes induced by mechanics stimulus].
AB  - OBJECTIVE: To study the effects of Bushen Zhuangjin Decoction (BZD) containing
      serum on the apoptosis of chondrocytes induced by mechanics stimulus. METHODS:
      The BZD containing serum was extracted. The chondrocyte nutritive media was
      divided into 3 groups, i.e., the common nutritive medium group, the blank rabbit
      serum medium group, and the BZD nutritive medium group. The apoptosis of
      chondrocytes was induced by continuing mechanics stimulus in 24 h. Then the
      chondrocytes were collected. The apoptosis rate of chondrocytes was determined by
      flow cytometry. The contents of interleukin 1beta (IL-1beta) and nitric oxide
      (NO) in the corresponding media were determined. RESULTS: The apoptosis of
      chondrocytes in the BZD nutritive medium group (19.55 +/- 7.98)% was lower than
      that of the common nutritive medium group (39.32 +/- 13.45)% and the blank rabbit
      serum medium group (37.87 +/- 9.67)%, showing statistical difference (P < 0.05).
      The contents of IL-1beta and NO were also lower in the BZD nutritive medium group
      with statistical difference when compared with those of the other two groups (P <
      0.05). CONCLUSION: BZD containing serum could protect mechanics stimulus induced
      apoptosis of chondrocytes.

PMID- 22978106
TI  - [Effects of arsenic trioxide on the proliferation of human breast cancer SKBR-3
      cell and the expression of Notch1].
AB  - OBJECTIVE: To study the effects of arsenic trioxide (As2O3) on the proliferation
      and the migration force of human breast cancer SKBR-3 cell and the expression of
      Notch1. METHODS: SKBR-3 cells were cultured with different concentrations of
      As2O3 for 24 h and with the final concentration of 8 micromol/L for 24, 48, and
      72 h. The effects of As2O3 on the cell proliferation of SKBR-3 were detected by
      MTT assay. The effects of the migration force of SKBR-3 cells were detected by
      Transwell. The expression of Notch1 mRNA was detected using reverse transcription
      polymerase chain reaction (RT-PCR). The expression of Notch1 protein was detected
      using Western blot. RESULTS: As2O3 could significantly inhibit the proliferation
      of SKBR-3 cells in a concentration- and time-dependent manner (P < 0.05). It also
      could inhibit the migration force of SKBR-3 cells (P < 0.05). Results of RT-PCR
      and Western blot showed that Notch1 mRNA and protein levels obviously decreased
      (P < 0.05). CONCLUSION: As2O3 could inhibit the expression of Notch1 and the cell
      proliferation and the migration force of SKBR-3 cells, which primarily revealed
      that As2O3 might affect the biological behavior of human breast cancer cells
      possibly through Notch1 signaling pathway, thus providing theoretical and
      experimental bases for treating breast cancer by arsenic.

PMID- 22978107
TI  - [Effects of soybean isoflavones on RAGE mediated signal transduction in the
      hippocampus of rats with Alzheimer's disease].
AB  - OBJECTIVE: To investigate the effects of soybean isoflavones on receptor for
      advanced glycation end products (RAGEs) mediated signal transduction in the
      hippocampus of rats with Alzheimer's disease (AD). METHODS: AD rat model was
      established by bilateral hippocampus injection of amyloid beta25-35 (Abeta25-35).
      Sixty rats were equally randomized into 5 groups, i.e., the model group, the high
      dose soybean isoflavones group (at the daily dose of 30 mg/kg), the low dose
      soybean isoflavones group (at the daily dose of 10 mg/kg), the estrogen group (at
      the daily dose of 0.4 mg/kg), and the sham-operation control group. Three days
      after modeling 2 mL soybean isoflavones or estrogen was respectively
      administrated to rats in the high dose soybean isoflavones group, the low dose
      soybean isoflavones group, and the estrogen group by gastrogavage. Equal volume
      of 0.5% CMC-Na was administered to rats in the model group and the sham-operation
      group. The treatment lasted for 21 days. The contents of RAGE and interleukin-6
      (IL-6) in the hippocampus were measured by ELISA. The activity of cysteine
      containing aspartate-specific protease-3 (Caspase-3) was measured by
      spectrophotometry. The expressions of phosphorylation extracellular signal
      regulated kinase1/2 (P-ERK1/2) in the hippocampus were measured by
      immunohistochemical assay. RESULTS: Compared with the model group, soybean
      isoflavones could significantly decrease the contents of RAGE and IL-6, the
      activity of Caspase-3, and the phosphorylation level of ERK1/2 in the hippocampus
      of AD model rats (P < 0.01). CONCLUSION: Soybean isoflavones could down-regulate
      RAGE mediated inflammatory signal transduction in the hippocampus of AD rats,
      attenuate the inflammatory reactions, reduce the neurotoxicity of Abeta, and
      resist the apoptosis of hippocampal neurons.

PMID- 22978109
TI  - [Comparative assessing the effects of angelica root and chuanxiong on the
      hemorheology and the blood coagulation function in acute blood stasis rats].
AB  - OBJECTIVE: To comparatively assess the effects of angelica root and chuanxiong on
      the hemorheology and the blood coagulation function in acute blood stasis rats.
      METHODS: Ice water bath and subcutaneous injection of adrenaline were both used
      to establish the acute blood stasis rat model. The whole blood viscosity, plasma
      viscosity, erythrocyte sedimentation rate (ESR), and haematocrit were tested to
      observe the effects of angelica root and chuanxiong on the hemorheology of blood
      stasis rats. The prothrombin time (PT), activated partial thromboplastin time
      (APTT), and plasma fibrinogen (FIB) were tested to observe the effects of
      angelica root and chuanxiong on the blood coagulation function of blood stasis
      rats. Finally all those indices were integrated to the total activating blood
      circulation effect value to assess the total effects of angelica root and
      chuanxiong on activating blood circulation and dissipating blood stasis. RESULTS:
      Compared with the normal control group, the hemorheological indices obviously
      increased, PT and APTT were obviously shortened, and the FIB content obviously
      increased in the model group. Compared with the model group, the water extracts,
      alcohol extracts, water-alcohol extracts of angelica root, chuanxiong, angelica
      root and chuanxiong 1:1, and angelica root and chuanxiong 1.5:1 could decrease
      the hemorheological indices, prolong the PT and APTT, and significantly reduce
      the content of FIB. Under the condition of the same preparation method, the
      alcohol extract of angelica root and chuanxiong 1:1 showed the best total effect.
      As for the single herbs, chuanxiong had better effect than angelica root on the
      total effects of activating blood circulation and dissipating blood stasis. Under
      the condition of the same ratio, the alcohol extracts of angelica root and
      chuanxiong showed better total effects of activating blood circulation and
      dissipating blood stasis than water extracts and water-alcohol extracts.
      CONCLUSION: The angelica root and chuanxiong could obviously improve the
      abnormality of hemorheology and blood coagulation function in acute blood stasis
      rats, thus providing evidence for revealing the scientific innovation of the
      compatibility of angelica root and chuanxiong.

PMID- 22978108
TI  - [Effects of sand treatment in Uyghur medicine on caspase-3, Bcl-2, Bax, and the
      apoptotic expression in the cartilage of rabbit knee osteoarthritis model].
AB  - OBJECTIVE: To study the effects of sand treatment on cysteine aspartate-specific
      proteinase-3 (Caspase-3), B-cell leukemia-lymphoma-2 (Bcl-2), Bcl-2-associated X
      protein gene (Bax) in the articular cartilage of rabbit knee osteoarthritis (OA),
      and the apoptotic protein expression, thus providing theoretical evidence for
      sand treatment in Uyghur medicine. METHODS: The OA animal model was established
      by fixing right hind limbs with gypsum in 22 New Zealand rabbits. Of them, 2
      original model rabbits were taken as the control group, while the rest 20 were
      randomly divided into a free running group and a sand treatment group, 10 in each
      group. The healthy side of the free running group was taken as the normal control
      group. The sand treatment was given to those in the sand treatment group for 20
      days. The expressions of Caspase-3, Bcl-2, and Bax in the cartilage cells of
      rabbit knee joint were measured by immunohistochemical assay. The cell apoptosis
      of chondrocytes was detected using terminal deoxynucleotidyl transferase mediated
      dUTP nick end labeling (TUNEL). RESULTS: Compared with the normal control group,
      the positive cell number, the optical density (OD), the protein expressions of
      Caspase-3, Bax, and TUNEL were higher in the free running group and the sand
      treatment group (P < 0.01). Besides, they were obviously higher in the free
      running group than in the sand treatment group (P < 0.01). The positive cell
      number of Bcl-2 and OD value in the free running group and the sand treatment
      group were both lower than those of the normal control group (P < 0.01). The
      positive cell number was obviously higher in the sand treatment group than in the
      free running group (P < 0.01). CONCLUSION: Sand treatment could inhibit the
      expressions of Caspase-3, Bax/Bcl-2, and TUNEL in the articular cartilage of
      rabbits' knee OA, which might be partial mechanisms for anti-inflammation of sand
      treatment.

PMID- 22978110
TI  - [Effects of Bufei Jianpi Recipe on the diaphragmatic neural discharge and the
      diaphragmatic muscle function in rats with chronic obstructive pulmonary
      disease].
AB  - OBJECTIVE: To observe the effects of Bufei Jianpi Recipe (BJR) on the
      diaphragmatic neural discharge and the diaphragmatic muscle function in rats with
      chronic obstructive pulmonary disease (COPD). METHODS: Rats were randomly divided
      into the normal control group, the model group, the high dose BJR group (9.68
      g/kg x d(-1)), the medium dose BJR group (4.84 g/kg x d(-1)), the low dose BJR
      group (2.42 g/kg x d(-1)), and the aminophylline group (2.3 mg/kg x d(-1)). The
      stable phase COPD rat model was prepared using repeated smoke inhalations and
      bacterial infections. The high, medium, and low dose BJR and aminophylline was
      respectively administered to rats from the ninth week to the twentieth week. The
      sampling was taken. The lung function, diaphragmatic neural discharge time (Td),
      and diaphragmatic neural discharge interval (Tdi), diaphragmatic neural discharge
      range (Rd), diaphragmatic neural discharge area (Ad), expiratory time (Tex),
      inspiratory time (Tin), respiratory rate (RR), respiratory excursion (RE),
      respiratory area (RA), and diaphragmatic muscular tension and endurance were
      detected. RESULTS: Compared with the normal control group, the tidal volume (TV),
      peak expiratory flow (PEF), and 50% tidal volume expiratory flow (EF50)
      significantly decreased in the model group (P < 0.01). Td, Tdi, Tex, and Tin were
      significantly prolonged (P < 0. 05, P < 0.01). Ad, Rd, RR, RE, RA, diaphragmatic
      muscular tension and endurance significantly decreased (P < 0.05, P < 0.01). The
      ratio of type I and IIA diaphragmatic fibers significantly increased and type IIB
      significantly decreased (P < 0.01). The activity of ATP decreased and the
      activity of SDH increased (P < 0.01). The aforesaid indices were improved to
      different degrees in BJR groups, especially in the high dose BJR group and the
      medium dose BJR group (P < 0.05, P < 0.01). CONCLUSIONS: BJR could significantly
      improve the diaphragmatic neural discharge and the diaphragmatic muscle function.
      Its efficacy was better than that of aminophylline.

PMID- 22978111
TI  - [Effects of Zengmian Yiliu Recipe combined cisplatin on the tumor inhibition rate
      in platinum-resistant ovarian cancer].
AB  - OBJECTIVE: To observe the effects of Zengmian Yiliu Recipe (ZYR) combined
      cisplatin on the growth of subcutaneous tumor in nude mice with platinum
      resistant ovarian cancer, and to explore its possible mechanisms. METHODS: The
      model of ovarian cancer subcutaneous tumor was established in nude mice using
      platinum-resistant ovarian cancer line COC1/DDP. The mice were randomly divided
      into six groups, i. e., the high Chinese materia medica (CMM) group, the medium
      CMM group, the low CMM group, the cisplatin group (DDP), the combined treatment
      group (with DDP combined CMM), and the control group (with normal saline). The
      medication lasted for 3 successive weeks. The tumor weight and the tumor
      inhibition rate were calculated. The expressions of Bcl-associated x protein
      (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) were detected using quantitative RT
      PCR and immunohistochemical assay. The ultra-structure of tumor cells was
      observed by electron microscopy. RESULTS: The tumor inhibition rate was the
      highest in the combined treatment group, being (59. 26 +/- 6.86) %, showing
      statistical difference when compared with the rest groups (P < 0.01). Results of
      RT-PCR showed the Bax mRNA expression was the highest in the combined treatment
      group and the lowest in the control group (P < 0.01). Anti-apoptotic gene Bcl-2
      mRNA expression was the highest in the control group and the lowest in the high
      CMM group (P < 0.01). The Bcl-2 mRNA expression was lower in the combined
      treatment group than in the cisplatin group (P < 0.01). Immunohistochemical
      results showed the Bax protein expression was the highest and the expression of
      Bcl-2 was the lowest in the combined treatment group, showing statistical
      difference when compared with the rest groups (P < 0.01). The middle- and late
      stage manifestations of apoptosis could be seen in each CMM group and the
      combined treatment group under electron microscope. CONCLUSIONS: ZYR combined
      with chemotherapy could reverse the cisplatin-resistance of resistant ovarian
      cancer nude mice, and enhance its tumor inhibitory effect. Its mechanisms were
      correlated with up-regulating the expression of Bax, down-regulating the
      expression of Bcl-2, and promoting cisplatin resistant ovarian cancer cell
      apoptosis.

PMID- 22978113
TI  - [Di'ao Xinxuekang set a precedent for drugs with China's independent intellectual
      property rights to enter the European and American markets].

PMID- 22978112
TI  - [Effects of administration and local application of epimedium on the fracture
      healing in osteoporosis rats].
AB  - OBJECTIVE: To study the effects of administration or local application of
      epimedium on the fracture healing in osteoporosis rats. METHODS: Eighty-two 4
      month old clean female rats, 210-250 g, were randomly divided into the
      experimental group (n = 75) and the control group (n = 7). The bilateral ovaries
      were resected in the experimental group, while only little fat tissue around the
      ovary was resected in the control group. Ten weeks after operation the
      osteoporosis model was successfully established verified by bone densitometry and
      scanning electron microscopy (SEM). The femur fracture models were established in
      the rest 72 rats of the experimental group. They were randomly divided into 3
      groups, 24 in each group, i.e., the calcium phosphate cement (CPC) group (Group
      A), the CPC-epimedium group (Group B), and the epimedium administration group
      (Group C). The serum alkaline phosphatase (ALP) levels of the 3 groups were
      determined 2, 4, 8, and 12 weeks after surgery. The vitodynamical test and
      observation of the histological section were performed. RESULTS: The serum ALP
      levels increased to some extent in the 3 groups 2, 4, and 8 weeks after bone
      fracture surgery. But the increase was more obvious in Group B with statistical
      difference shown when compared with Group A and C (P < 0.05). The ALP level in
      Group B decreased to the normal range till the 12th week. The bone fracture had
      not completely healed in Group C and A. Their ALP levels decreased to some
      extent, but were still maintained to a comparatively higher level, showing
      statistical difference when compared with that of Group B (P < 0.05). These
      results were agreeable with the results of the histological observation. Better
      bone activity promoting results were shown in Group B. The vitodynamical test
      results of the femur of Group B were all higher than those of Group A and C at
      each time point (P < 0.05). CONCLUSIONS: Local application of epimedium could
      accelerate the fracture healing in osteoporosis rats. It showed better effects
      when compared with oral administration at the same dose.

PMID- 22978114
TI  - [The opportunities and challenges of Chinese medicine and pharmacy in intervening
      HIV drug resistance].
AB  - AIDS is a serious threat to the human health. Although highly active anti
      retroviral therapy (HAART) has obviously prohibited the progress of AIDS, a
      yearly increasing problems of human immunodeficiency virus (HIV) drug resistance
      have arousing more attention, affecting the clinical efficacy of HAART, and even
      resulting in treatment failure. We are lack of exchangeable medicines, while the
      therapeutic course of AIDS treatment is longer. It is not feasible to monitor and
      detect the drug resistance of medicine takers by taking the exchangeable
      medicines as the outcome. Better indications have been obtained by combining the
      experiences for Chinese medicine and pharmacy (CMP) intervention and CMP's
      intervening HIV drug resistance by clinical trails. Based on retrospective
      studies on the HIV biological features, reasons for HIV drug resistance, the
      occurrence, the predisposing population, and the mutation sites, the authors
      addressed it is a good opportunity for CMP in intervening HIV drug resistance at
      present situation in China. Meanwhile, the authors also raised too much
      difficulties and challenges. We hope CMP's intervention can minimize and delay
      the generation of drug resistance to the utmost, solve key problems in HIV/AIDS
      prevention and control in China.

PMID- 22978115
TI  - [The application of metabonomics in modern studies of Chinese materia medica].
AB  - Metabonomics, a newly developing subject secondary to genomics, transcriptomics,
      and proteomics, is an important constituent part of systems biology. It is
      believed to be the final direction of the systems biology. It can be directly
      applied to understand the physiological and biochemical states by its "metabolome
      profile" as a whole. Therefore, it can provide a huge amount of information
      different from those originating from other "omics". In the modernization of
      Chinese materia medica research, the application of metabonomics methods and
      technologies has a broad potential for future development. Especially it is of
      important theoretical significance and application value in holistic efficacies
      evaluation, active ingredients studies, and safety research of Chinese materia
      medica.

PMID- 22978116
TI  - [Developing integrative medicine should pay attention to basic research].
AB  - After over five decades of vigorous development in China, integrative medicine
      (IM) has developed into an academic discipline with some overlaps but independent
      from both Chinese medicine (CM) and Western medicine (WM). CHEN Zhu, the Minister
      of the Ministry of Health pointed out that IM represents the developing direction
      for future medicine at the conference commemorating the 50th anniversary of
      Chairman MAO Zedong' s important instructions on WM doctors learning from CM,
      which was sponsored by State Administration of Traditional Chinese Medicine and
      Chinese Association of Integrative Medicine in Beijing on November 27,2008. In
      this article, the author stresses basic research should be paid attention to in
      developing IM from the concepts and connotation, development and evolution,
      achievements and problems, layers and pathways of IM.

PMID- 22978117
TI  - [Dynamic study of correspondence of prescription and syndrome system: a system
      with combination of disease and syndrome, correspondence of prescription and
      syndrome].
AB  - By analyzing the present situation and existing problems in the material bases of
      syndrome and Chinese materia medica, we think that either syndrome or
      prescription is a complex whole system. Studies of the material bases of syndrome
      and prescription should be established on the combination of disease and
      syndrome, following the holistic and dynamic principles. Departure from the
      holistic principle, separating the syndrome from the prescription, ignoring the
      dynamic concepts may possibly lose the features and advantages of syndrome typing
      and Chinese medicine preparations. The metabolomics research bridges the study of
      prescription and syndrome. It is of great significance in finding out the
      agreeable point of disease-syndrome-efficacy, establishing a dynamic research
      method with combination of disease and syndrome, correspondence of prescription
      and syndrome.

PMID- 22978118
TI  - [Literature study on the syndrome diagnosis and classification of coronary artery
      disease].
AB  - To investigate the application of diagnosis methods for coronary artery disease
      (CAD) and the status quo of its syndrome typing. The literature content analysis
      was used in this study. The frequency statistics was performed by comprehensively
      collecting CAD (thoracic obstruction) syndrome typing correlated literatures,
      designing content analysis tables, extracting information such as typing methods,
      typing elements, and syndrome typing, and so on. Results showed that blood
      stasis, yin deficiency, qi deficiency, yang deficiency, phlegm turbidity, and
      other syndrome elements extensively exist in literatures concerning CAD syndrome
      typing. Modem doctors prefer to use syndrome typing of qi, blood, jinye, and
      eight principles in syndrome typing of CAD more frequently. The asthenia in
      origin and asthenia in superficiality has been widely recognized as the basic
      syndrome of CAD.

PMID- 22978119
TI  - [Exploring a new mode of integrative medicine information service].
AB  - With the significant and continuous growth of the research and application of
      complementary and alternative medicine (CAM) all over the world, the demand for
      medical information services has been increasing correspondingly. However, the
      barriers of accessing and utilizing non-English literature, and the barrier of
      language have blocked English speaking clinicians and researchers of CAM from
      obtaining high quality and authoritative medical evidence from the non-English
      medical resources. This article, with introducing the UCLA Information Center for
      East-West Integrative Medicine, will demonstrate a new collaborative mode of
      integrative medicine information service between China and the US, and discuss
      the perceived challenges.

PMID- 22978120
TI  - [Different translations for the same wording, a phenomenon in English translation
      of Chinese medicine terminology from approach of translation as adaptation and
      selection].

PMID- 22978121
TI  - [The current state and prospect of studies on ventricular remodeling by Chinese
      medicine and pharmacy].

PMID- 22978122
TI  - [The cellular and molecular biological mechanisms for the wound healing by
      Chinese medicine and pharmacy].

PMID- 22978123
TI  - [Julie Poirier. On the front line].

PMID- 22978124
TI  - [September is arthritis month].

PMID- 22978125
TI  - [The Office of Handicapped Persons of Quebec and nurses. Unrecognized services].

PMID- 22978126
TI  - [Social drinking].

PMID- 22978127
TI  - [Alcoholic cardiomyopathy. How does the heart react to alcohol abuse?].

PMID- 22978128
TI  - [SIDIIEF: the francophone voice of the nursing profession in the international
      community].

PMID- 22978129
TI  - [University nursing education. A unanimous vote in favor of the Geneva
      Declaration].

PMID- 22978130
TI  - [Address of The University Agency of French-speaking communities. It represents
      nearly 800 universities, and supports the Geneva Declaration].

PMID- 22978131
TI  - [West Nile virus. A record number of cases in Quebec in 2011].

PMID- 22978132
TI  - [Abortion. The taboo of bereavement].

PMID- 22978133
TI  - [Pregnancy interruption. What are the beliefs that restrict or benefit nurses in
      the context of a pregnancy interruption?].

PMID- 22978134
TI  - [Chronic inflammation and cardiovascular disease. A stronger and stronger link].

PMID- 22978135
TI  - [Ignoring an acute COPD exacerbation. Breaking the silence].

PMID- 22978136
TI  - [Fifty year longitudinal study of labor patterns].

PMID- 22978137
TI  - [Emergency medicine. The longer one waits, the higher the risk].

PMID- 22978138
TI  - [Zelboraf. Longer term survival for advanced stage melanoma].

PMID- 22978139
TI  - [Velcade for multiple myeloma. A new method of administration].

PMID- 22978140
TI  - [Onbrez breezhaler to control chronic obstructive pulmonary disease].

PMID- 22978141
TI  - [Fampyra for multiple sclerosis].

PMID- 22978143
TI  - Health literacy: help missing in the new health reform act?

PMID- 22978142
TI  - The Patient Protection and Affordable Care Act: is it really affordable?

PMID- 22978144
TI  - How will the SCOTUS decision on ACA affect my practice?

PMID- 22978145
TI  - Health care reform meets the Supreme Court: what happened?

PMID- 22978146
TI  - The Tennessee Surgical Quality Collaborative: a model for improving quality of
      care and reducing health care costs.

PMID- 22978147
TI  - Coping with medical malpractice stress, part II.

PMID- 22978148
TI  - The question of Medicaid expansion: Tennessee faces a difficult decision.

PMID- 22978150
TI  - The day I became a physician.

PMID- 22978149
TI  - TMA: the view from 40,000 feet (40 years), part II.

PMID- 22978151
TI  - Tennessee's county health councils: partnerships to improve the public's health.

PMID- 22978152
TI  - Individual and system-related factors associated with the costs of intellectual
      and developmental disabilities.
AB  - The factors associated with the cost of intellectual and developmental
      disabilities are the prevalence of pervasive developmental disorders, limited
      access to specialized services, the high cost of prescription medication,
      strained relationships with providers, and not enough latitude when it comes to
      selection of services. These factors work together to create an environment that
      is either conducive to or prohibitive of quality patient outcomes and improved
      perceptions of publicly-provided health care. Improving any of these factors
      would undoubtedly lower the overall annual cost. However, more research is
      required to understand how these factors affect both cost and perceptions. The
      factors addressed in this paper are the difference between mental healthcare and
      general healthcare; the prevalence of intellectual and developmental
      disabilities; the sociological impact of Medicaid services; out-of-pocket
      expenses; use of specialized mental health services; access to specialized
      services; and patients' relationship with providers.

PMID- 22978153
TI  - [Variation and evolution analysis of the PB1-F2 genes of novel influenza A
      viruses isolated from Guangzhou China].
AB  - To compare and analyze the variation of PB1-F2 genes of Influenza A Viruses from
      Guangzhou during 2009 to 2011 with the Influenza A Viruses from all over the
      world, to lay the foundation of functional research and interaction mechanism of
      the PB1-F2 protein. 17 Novel H1N1 influenza viruses and 1 seasonal H1N1 influenza
      virus have been isolated from human in Guangzhou during 2009 to 2011 that were
      cloned into pMD 18-T Vector for sequencing. Then, 68 PB1-F2 genes of IAVs from
      human around the world were downloaded from GenBank database and analyzed using
      molecular biological software. The phylogenetic tree result shows that the PB1-F2
      genes of IAV from the world separated into two main groups. There is high
      homology of PB1-F2 genes of one Seasonal H1N1 virus and Novel H1N1 viruses which
      were isolated in Guangzhou compared with the global Novel H1N1 viruses. And all
      of them got the 11 amino acids truncated protein by mutation included one
      seasonal H1N1 strain isolated by our laboratory. There is no variation of PB1-F2
      genes of Novel H1N1 virus in Guangzhou compared with the worldwide strains.
      However, one seasonal H1N1 virus which isolated by our laboratory shows analogous
      truncated mutation of PB1-F2 of Novel H1N1 virus, it reveals that the PB1-F2 gene
      might has done the early reassortment between the Novel H1N1 virus and seasonal
      H1N1 virus.

PMID- 22978154
TI  - [Establishing a high-titer infectious avian influenza A (H5N1) pseudotyped viral
      particle].
AB  - A transient four-plasmid cotransfection system was used to construct avian
      influenza A (H5N1) pseudotyped viral particle (H5N1Pp) by incorporating
      hemagglutinin (HA) protein and neuraminidase (NA) protein from H5N1 avian
      influenza virus onto Murine leukemia virus pseudotyped viral particles, the
      transmission electron microscopy, infectivity titer assay, hemagglutination
      assay, neutralization assay of H5N1Pp were studied. We established a pseudotyped
      H5N1 viral particle at a high titer of 10(8) Pp/mL, the morphology,the
      hemagglutination activity and neutralization specificity of H5N1Pp is simililar
      to wild H5N1 virus. The research result sets a platform for studying this virus,
      including its receptors, the functional analysis of HA and NA, neutralizing
      antibodies and anti-H5N1 drug development.

PMID- 22978155
TI  - [Molecular evolution of human influenza H3N2 virus hemagglutinin genes in
      Guangdong China].
AB  - The molecular characterization and phylogenetic analysis of hemagglutinin (HA)
      genes of human influenza H3N2 viruses in Guangdong, China from 2007 to 2010 were
      studied in this study. By space-time sampling of strains, the HA genes of H3N2
      strains from Guangdong were sequenced and searched from Internet, and then the
      variation and evolution of HA genes were conducted by Lasergene 7.1 and Mega 5.05
      and evolutionary rates were analyzed by epidemiological data. The phylogenetic
      tree was established by alignment of 17 Guangdong strains and 26 global reference
      strains. Ks rates and Ka rates of HA genes were 2.06 x 10(-3)-2.23 x 10(-3)
      Nt/Year and 1.05 x 10(-3)-1.21 x 10(3) Nt/Year during 2007-2010, while the
      velocity of HA1 evolution of Ka was 3. 13 times than that of HA2 evolution.
      Compared with HA of vaccine strain A/Perth/16/2009, the genetic homologies of
      Guangdong strains in 2009 reached to 98.8%-99.7% and of Guangdong strains in 2010
      reached to 98.0%-98.4%. There were some amino acid substitutions in five epitope
      regions of HA1 during 2007-2010, especially in B region (N160K) and D region
      (K174R/N); the K189E/N/Q and T228A in RBS (receptor-binding site) occurred in
      2010 as two glycoproteins sites substituted impacted on the HA1 antigenicity. The
      antigenicity of epidemic H3N2 strains in 2010 was to some degree different that
      of the vaccine strain A/ Perth/16/2009. According to that there were variations
      of B and D epitopes and two sites of RBS and two glycoprotein in Guangdong H3N2
      HA1 genes, WHO/ CDC should recommend new representative strains during 2011-2012
      influenza seasons if H3N2 HA genes further evolve in the near future.

PMID- 22978156
TI  - [Quasispecies sequence analyses of envelope protein E1/E2 coding genes from four
      Chinese HCV patients and identification of a novel insertion mutation of HCV].
AB  - This paper investigated the envelope protein E1/E2 quasispecies genetic
      characterization of 4 HCV positive sera (Genotype 1b: 274, 366, 383; Genotype 2a:
      283) in China. Nucleotide acid was extracted and glycoprotein E1/E2 (191-764aa)
      coding genes were obtained by RT-PCR, positive clones were randomly selected for
      sequencing. The phylogenetic relationships and the homology of nucleotide and
      amino acid were analyzed based on E1/E2 coding genes, and some vital functional
      regions of E1/E2 were characterized. A total of 43 sequences (274: 10; 283: 12;
      366: 13; 383: 8) were obtained showing high genetic heterogeneity in HVR1 and
      HVR2 regions, while sequences of the neutralizing epitopes, transmembrane domain
      I, II and N-terminal ectodomain were comparatively conservative. Single base (C)
      insertion mutation at nt1279 ( E1 region, aa313), resulting in a mutated E1
      coding protein (beginning at aa 313) and interruption at N terminus (aa 398) of
      HVR1 region of E2, was dominant quasispecies sequence(11/12) found in serum 283 .
      This is the first report on E1/E2 quasispecies in Chinese HCV patients and this
      novel pattern of insertion mutation provides important information for further
      study on HCV pathogenesis and immune evasion.

PMID- 22978157
TI  - [Subtype and sequence analysis of gag gene of HIV-1 among men who have sex with
      men in Zhengzhou, Henan Province].
AB  - To investigate the subtype distribution of human immunodeficiency virus-1(HIV-1)
      infection among men who have sex with men (MSM) in Zhengzhou, Henan Province,
      forty blood samples were collected from HIV-1 carriers, who acknowledged to have
      sex with men. The complete gag gene was amplified by RT-PCR and nested-PCR and
      sequenced. All sequences were edited by BioEdit and subtyped by genotyping
      software. Phylogenetic analysis of gag gene were then performed using the MEGA
      3.1 software, the gene distances were calculated by Distance program. There were
      three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among
      twenty four MSMs in Zhengzhou. Genotyping results showed that 33.33% (8/24) were
      B, 41.67% (10/24) were CRF01-AE and 25% (6/24) were CRF07-BC, and subtype CRF01
      AE had become the most prevalent HIV-1 subtype in Zhengzhou, Henan province. In
      conclusion, recombinant HIV-1 strains are circulating in Henan province and the
      epidemiology is complicated.

PMID- 22978158
TI  - [Analyses on antigen epitopes and drug resistance mutations of HIV-1 gag and pol
      genes].
AB  - To study the CTL antigen epitopes and drug resistance mutations of HIV-1 gag and
      pol genes through analyzing gag and pol gene sequences. The HIV-1 gag and pol
      gene fragments were amplified using nested polymerase chain reaction. A total of
      23 PCR sequences, 449 cloned gag sequences and 402 cloned pol sequences were
      obtained. Sequence analyses showed the 23 samples were subtype B or B'. A total
      of 4 in 8 CTL antigen epitopes appeared 8 mutations in consensus sequence of
      subtype B and B'. There were no mutations found in the PCR sequences, whereas a
      few mutations were found in clone sequences (9.80%) in 5 antigen epitopes in p24
      region. Eighteen PIs-related mutations and 24 RTIs-related mutations were found
      in PCR sequences and clone sequences in pol gene region, in which 17 (94.44%) PIs
      related mutations and 15 (62.50%) RTIs-related mutations were found only in the
      clone sequences, respectively. The results showed that the prevalence of HIV-1
      drug resistance strains in this study was at a higher level (17.39%), suggesting
      that some samples were resistant.to existing antiviral drugs.

PMID- 22978159
TI  - [Identification of Env-specific monoclonal antibodies from Chinese HIV-1 infected
      person by B cell activation and RT-PCR cloning].
AB  - To obtain protective human monoclonal antibody from HIV-1 infected person, we
      adapted a technology for isolating antigen specific monoclonal antibody from
      human memory B cells through in vitro B cell activation coupled with RT-PCT and
      expression cloning. Human B cells were purified by negative sorting from PBMCs of
      HIV-1 infected individuals and memory B cells were further enriched using anti
      CD27 microbeads. Two hundred memory B cells per well were cultured in 96-well
      round-bottom plates Env-specific antibodies in supernatants were with feeder
      cells in medium containing EBV and CpG. screened by ELISA after 1-2 weeks'
      culture. Cells from positive wells of Env-specific antibody were harvested and
      total RNA was isolated. Human VH and Vkappa or Vlambda genes were amplified by RT
      PCR and cloned into IgG1 and kappa or lambda expressing vectors. Functional VH
      and Vkappa or Vlambda were identified by cotransfecting 293T cells with
      individual heavy chain and light chain clones followed by analysis of culture
      supernatants by ELISA for Env-specific antibodies. Finally, corresponding mAb was
      produced by transient transfection of 293T cells with the identified VH and
      Vkappa/lambda pair and purified by protein A affinity chromatography. Purified
      monocolonal antibodies were used for HIV-1 specific antibody-dependent cell
      mediated cytotoxicity (ADCC) and neutralizing activity assay. Four monocolonal
      Env-specific antibodies were isolated from one HIV-1 subtype B' infected
      individual. Two of them showed strong ADCC activity and one showed weak
      neutralizing activity against HIV-1. Its further studies on their application in
      therapeutic or prophylactic vaccines against HIV-1 should be grounded.

PMID- 22978160
TI  - [Comparison between different gene and near full-length genome on the
      phylogenetic analyses of HIV-1 subtype B' in China].
AB  - This study aims to compare the influence of different genes to the results of HIV
      1 subtype B' phylogenetic analyses. We first split 47 near full-length genome
      sequences of subtype B' into different regions (gag, pol, vif, vpr, vpu, env,
      nef), which derived from various risk populations and geographic regions from
      Thailand, Myanmar and China from published studies. Phylogenetic analyses were
      performed to each region obtained. The phylogenetic results of different regions
      were compared to that of the near full-length genome sequences. The pol gene was
      found to have the lowest diversity and evolutionary rate, and could repeat the
      phylogenetic results by using near full-length genome sequences. Although the env
      gene has the highest diversity and evolutionary rate, it could not achieve the
      similar results. This study compared the influence to the results of HIV-1
      subtype B' phylogenetic analyses by using different genes and laid foundation for
      further molecular survey and analyses of the transmission of subtype B' in China.

PMID- 22978161
TI  - [The modified restriction of amino acids of HVR1, HVR2, HVR5, HVR7 in human
      adenovirus serotype 3 hexon].
AB  - The limitation of traditional Ad vectors result in wide application of capsid
      incorporation of antigens into adenovirus capsid proteins, but usually it can't
      rescue virus successfully when we engineered the hypervariable regions (HVRs) of
      hexon in adenovirus serotype 3(Ad3) vector. So we deleted or retained some amino
      acids in HVR1, HVR2, HVR5, HVR7 predicted by bioinformatics, constructed
      recombinant Ad3 vector pBRAddeltaE3GFP-mHexon, and transfected it into AD293 cell
      to confirm the influence on the virus rescue. These data of amino acids that can
      be deleted or retained in the HVRs of Ad3 vector should provide operating
      foundation for antigen capsid-incorporation strategy in human adenovirus serotype
      3, and also lay the groundwork for application of expressing foreign antigens in
      the hexon of human adenovirus serotype 3 as a platform of multivalent vaccine
      vectors.

PMID- 22978162
TI  - [Detection and genotyping of human bocavirus 2 in children with acute diarrhea].
AB  - To investigate the prevalence of HBoV2 in pediatric patients with acute diarrhea
      in Beijing and the characteristic of the genome of the virus, 553 stool specimens
      were collected from pediatric outpatients with acute diarrhea in Affiliated
      Children's Hospital of Capital Institute of Pediatrics during Nov. 2010 to Oct.
      2011. TaqMan-based Real-time polymerase chain reaction was performed to detect
      HBoV2 DNA from these specimens. Two positive specimens with high viral loads were
      selected for segmented amplification and then the amplified fragments were cloned
      into the plasmid vector pGEM-T, transformed into Escherichia coli DH5alpha and
      sequenced. Then genomic sequences assembled from those DNA fragments were
      compared with other parvovirus genomic sequences in the GenBank. Among these 553
      specimens tested, 15 (2.7%) were HBoV2 DNA positive. The highest positive rate
      was shown in July (7.0%) through the whole year and in 3-6 month age group (4.1%)
      among different age groups. All these 15 specimens positive for HBoV2 DNA were
      collected from patients younger than 2 years old, including 4 simultaneously
      positive for norovirus, 3 positive for rotavirus and 1 positive for adenovirus.
      By sequence analysis, 2 almost complete HBoV2 genomic sequences assembled from
      gene fragments amplified from specimens BJQ19 and BJQ390 were typical HBoV2. And
      they shared high homology with each other (99.2%), while they shared the highest
      homology with FJ375129 from Shanghai China (99.1% and 99.2%) among other
      parvoviruses. These data suggest that some of acute diarrhea in pediatric
      patients in Beijing were associated with HBoV2, and infants and young children
      aged from 3 months to 2 years, are more likely to be infected by HBoV2.

PMID- 22978163
TI  - [Genetic characteristics of EV71 in Yunnan Province from 2009 to 2010].
AB  - In order to learn about the genetic characteristic of human enterovirus type71
      (HEV71) isolated from cases of Hand, Foot and Mouth Disease (HFMD) in Yunnan
      Province from 2009 to 2010. 50 isolates form HFMD cases were performed entire VP1
      coding region amplification by reverse transcription-polymerase chain reaction
      and sequencing the nucleotide sequences; then the phylogenetic tree was
      constructed. The complete nucleotide sequences of region VP1 of the 50 strains
      were all 891nt length coding 297 amino acids. The result of molecular
      identification of the 50 strains is HEV71. Phylogenetic analysis indicated that
      48 EV71 isolates belonged to subgenotype C4a and 2 EV71 isolates belonged to
      genotype A. From 2009 to 2010, the pathogen of HFMD cases were EV71 strains in
      Yunnan province, which were co-evolved with isolates from other provinces in
      mainland of China. There was no significant difference found in the whole
      sequence of VP1 gene of the strains isolated from different regions or under
      different diseases occurred, but the spread of genetype A appared in Yunnan
      Province in 2009.

PMID- 22978164
TI  - [Full-length genome analysis of four genotype 3 letogenic Newcastle disease
      viruses isolated from different hosts].
AB  - The purpose of this study is trying to analysis the homology between four
      lentogenic Class I genotype 3 Newcastle disease virus isolates from different
      hosts with NDV strain NDV 08-004, which was the first obtained complete genome
      sequence virus of class I genotype 3. The full-length genome of NDV isolates,
      JS/3/09/Ch, ZJ/3/10/Ch, AH/2/10/Du and JS/9/08/Go,were determined by RT-PCR and
      then an alyzed. All the genomes are 15 198 nucleotides (nt) in length. Compared
      with the full genome sequences of Class II NDV stains (genotype IV-IX),four
      isolates has a 6-nt deletion in the non-coding region of nuclear phosphoprotein
      gene between nucleotides 1 640-1 641 and 12-nt insertion in the coding region of
      phospho protein gene between nucleotides 2 381-2 382. All the isolates have the
      motifs 112EQ/RQE/GRL117 at the cleavage site of the fusion protein, which is
      typical of lenogenic NDV strains, and it is in agreement with the result of
      pathogenic tests. The full-length genome of 4 genotype 3 NDV isolates shared 93%
      nucleotide identity with NDV08-004. The results of alignment of 6 viral genes
      showed that NP gene shared the highest identity (98.3%-96.4%) and P gene shared
      the lowest identity (96.1%-91.9%). The results show the following two points.
      First, it is concluded that the isolates from different hosts share the same
      genotype has the insignificant divergence in the genetic information. Second, it
      is proposed that the mutation rates of NP/F/L genes are lower than P/M/HN genes.

PMID- 22978165
TI  - [Genetic diversity of adenoviruses in bats of China].
AB  - Adenovirus remains a significant threat to public health. Recent studies showed
      that bats can harbor diverse adenoviruses. To further investigate the
      distribution and genetic diversity of bat adenoviruses in China, we collected
      throat and anal swab samples of 11 bat species from 6 provinces of China,
      including Beijing, Hunan, Jiangxi, Yunnan, Guizhou and Hainan. Nested PCR was
      used to identify potential bat adenoviruses from the samples, and positive
      results were cloned and sequenced for genetic diversity study. In addition,
      nucleotide sequence alignments based on corresponding amino acid sequence
      similarities were used for phylogenetic analyses. Our results showed that about
      20% of bat species in China are positive to adenoviruses, and Myotis ricketti is
      likely to be the most important host of bat adenoviruses in all locations.
      Moreover, we identified two diverse sequences of bat adenoviruses from the same
      sample of Ia io in Guizhou province of China. In general, the average nucleotide
      and amino acid sequence similarities of the conserved region of DNA polymerases
      of bat adenoviruses are 66.6% and 74.7%, respectively. The differences between
      bat species and their residences environments may have driven the adaptive
      evolution of the viruses, leading to the genetic diversity of the bat
      adenoviruses.

PMID- 22978166
TI  - [A redox process of ethanethiol group increases formation of beta-sheet structure
      and amyloid fibrils of wild type human prion protein].
AB  - In order to explore the potential influences of the disulfide bridge on the
      physical and chemical properties of PrP protein, the expressed recombinant human
      wild-type PrP protein was purified for using in an established redox process for
      the reduction and oxidation of the ethanethiol group within PrP. Sedimentation
      tests illustrated that redox process remarkably promoted the aggregation of
      recombinant PrP. Thioflavin T binding assay revealed an enhanced fibrillization
      of the recombinant human PrP after redox process. Far-UV circular dichroism
      demonstrated that the PrP treated with redox process showed a significant p-sheet
      rich structure. Furthermore, PrP-specific Western blot identified that the
      recombinant PrP after redox possessed stronger proteinase K-resistance. Those
      data indicates that the formation of the disulfide bridge induces the alteration
      of the secondary structure and enhances the progresses of aggregation and
      fibrillization of PrP protein.

PMID- 22978167
TI  - [Degradation of 14-3-3beta appeared in apoptosis cell induced by PrP106-126
      polypeptide].
AB  - To investigate changes of 14-3-3beta from apoptosis induced by PrP106-126
      polypeptide, HeLa cell was incubated with PrP106-126 for 4h or 8h. Nucleus
      changes and the expression of PARP were detected differently by Hoechst staining
      and Western blotting. Expressing of protein and mRNA from 14-3-3beta was
      determined by Western blotting and Real-time PCR. The results show that typical
      nucleus pyknosis and chip of apoptosis and degradation of PARP were induced by
      PrP106-126 peptide in HeLa cells. Degradation of 14-3-3beta appeared in apoptosis
      groups induced by PrP106-126 peptide. However, 14-3-3beta mRNA did not display
      any changes in apoptosis groups. This study indicated that degradation of
      antiapoptosis protein 143-3beta induced by PrP106-126 peptide may be one of
      pathogenesis mechanism of prion disease.

PMID- 22978168
TI  - [Identification and characterization of porcine bocavirus episomes].
AB  - To verify that the circular forms of bocavirus genome exist in their host,
      bocavirus episomes were detected in fecal samples of healthy piglets using a semi
      nested PCR method. Two species of porcine bocaviruses (PBoVG2-episome and PBoVG3
      episome) were identified for the first time. The relevant terminal sequences of
      the noncoding region (405 and 511 nt, respectively) were also obtained. Sequence
      analyses and secondary structure prediction indicated that the PBoVG2-episome was
      more similar to that of human bocavirus 3 (HBoV3) but the PBoVG3-episome was
      quite different from that of other members of the genus Bocavirus. Discovery of
      episomal forms of porcine bocaviruses (PBoV) suggested that PBoV, like HBoV, used
      a different replication mechanism from other parvoviruses. The sequencing of
      episome Inverted Terminal Repeats (ITRs) also contributes to a possible
      alternative strategy for constructing infectious molecular clones of bocavirus in
      a future study.

PMID- 22978169
TI  - [The development and application of a SYBR Green I real-time PCR assay for
      detection of infectious bursal disease virus].
AB  - To meet the needs of detection of infectious bursal disease virus (IBDV) under
      high efficient culture, a SYBR Green I real-time RT-PCR (qRT-PCR) was developed
      using a pair of primers specific to the conserved region of VP4 gene of IBDV and
      compared with TCID50 method by monitoring the proliferation dynamics of IBDV in
      DF-1 cell line adherent to micro carrier in tubular reactor. The results showed
      that the RT-PCRassay was linear in the range of 4. 03 X 10(1)-10(9)
      copies/microL. The IBDV RNA detection limit was 40 copies/microL, which was 1 000
      times more sensitive than conventional PCR. No cross-reactions with other viruses
      was observed. The intra-assay coefficient of variation was less than 0.05%. There
      was a parallel correlation of IBDV proliferation dynamics in DF-1 cell under
      Micro carrier suspension and static adherent culture by the qRT-PCR assay and
      TCID50 method. The detection results of the IBDV samples from tubular and flask
      culture showed the differences of the micro carrier and adherent culture by both
      methods. In conclusion, the qRT-PCR assay is more rapid and sensitive than the
      TCID50 method, which is more appropriate for the real time detection of IBDV.

PMID- 22978170
TI  - [The application of single-genome amplification and sequencing in genomic
      analysis of an attenuated EIAV vaccine].
AB  - Our previous studies found that the Chinese attenuated EIAV vaccine was composed
      of a pool of quasispecies, which showed a complicated diversity called "multi
      species". Further determining the viral composition of these species in the
      vaccine should improve the identification of predominant viruses in the vaccine
      and facilitate the analysis of in vivo evolution of EIAV and the vaccine. In this
      study, the comparison of fidelities in amplifying and sequencing the V3 to V5
      fragment of EIAV envelope gp90 gene by either a single-genome amplification (SGA)
      approach or the traditional RT-PCR (bulk PCR) was performed. Results revealed
      that the diversities were 1.84% and 1.88% for SGA- and bulk PCR-derived
      sequences, respectively. Futher analysis revealed that beside the sequences
      highly homologous to those derived by the bulk PCR, nine of 73 sequences derived
      by SGA contained a deduced amino acid domain that was identical to the
      corresponding domain in the virulent strain LN40. In addition, sequences with
      deletion of one predicted amino acid residual was detected by using SGA The
      presence of these less populated sequences provided additional evidence for the
      "multi-species" hypothesis for the action mechanism of the EIAV vaccine.
      Furthermore, based on the analysis of sampling bias, Our results that the
      difference in copy number of each viral specie in the pool of quasispecies
      resulted in the inefficiency to amplify viral sequences that were in low
      population by bulk PCR. Therefore, the sequences amplified by bulk PCR could not
      correctly represent the composition of quasispecies. As an approach based on the
      amplification and sequencing single isolated genome, SGA significantly improved
      the weakness of bulk PCR and appeared its advantage in analysis of EIAV genome
      composition with high variety.

PMID- 22978171
TI  - [Characterization of a novel podoviridae-phage infecting Serratia marcescens
      isolated in China].
AB  - Serratia marcescens jn01 was employed as the host for the isolation of phages
      from environmental sewage. One strain of phage named SmPjn was purified by
      picking transparent plaque with 2mm diameter and clear edge on the double-layer
      agar repeatedly. Electron micrographs indicated that the phage head was
      icosahedral with head size and tail length of (58 +/- 2.16) x (55 +/- 0.47) nm
      and (7 +/- 1.25) nm, respectively. On the basis of the morphology, this phage
      belongs to the family Podoviridae. Host-range determination revealed that the
      phage was capable of infecting the other two isolates of S. marcescens, P25 and
      CMCC41002. The optimal multiplicity of infection was 1. A one-step growth curve
      of SmPjn indicated that the latent period and burst size were estimated at 50 min
      and 1,125 pfu/cell, respectively . Genomic DNA of SmPjn was above 27kb in size
      and could be digested by Hind Ill and EcoR I into 11 and 9 visible fragments
      after electrophoresis, respectively. A novel Podoviridae-phage infecting S.
      marcescens was firstly reported in China.

PMID- 22978172
TI  - [Advances in the structure and function of pandemic A/H1N1/2009 influenza virus
      HA protein].
AB  - Since March 2009, pandemic A/H1N1/2009 influenza virus has been spreading
      throughout many countries including China. The emerged virus caused great harm to
      human health and social economy. Hemagglutinin (HA) is the most important viral
      surface glycoprotein, mainly possessing three kinds of functions: (1) binding to
      host cell receptor, (2) triggering the fusion between viral envelop and target
      cell membrane, (3) stimulating the body to generate the neutralizing antibody.
      Advances in the structure, primary function, evolution and antigenicity of
      pandemic A/H1N1/2009 influenza virus HA protein are reviewed in this paper.

PMID- 22978173
TI  - [Modulation of the host toll-like receptor signaling pathways by virus
      infection].
AB  - Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors
      (PRRs) that play a central role in host cell recognition and responses to virus
      infection, leading to the production of interferons (IFNs) and proinflammatory
      cytokines. In parallel, in order to establish an infection, viruses have to
      develop exclusively strategies to interfere with TLRs signaling, particularly
      some important adaptors activation such as MyD88, NF-kappaB, TRIF and IRFs, and
      suppress or escape host's antiviral immune response. In this paper, we review the
      latest findings on the various strategies used by viruses to modulate TLRs
      mediated innate immune response, with special emphasis on immune evasion
      mechanism of VACV, HCV and HIV. By highlighting recent progress in these areas,
      we hope to convey a greater understanding of how viruses hamper TLRs signaling
      and how to overcome viral infection.

PMID- 22978174
TI  - [Function of tumor suppressor p53 and its role in antiviral immunity].
AB  - Tumor suppressor p53, known as 'the guardian of the genome', has the ability to
      prevent the emergence of transformed cells by the induction of cell cycle arrest
      and apoptosis. Otherwise, there were researches about the function of p53, such
      as NDA repair, regulating metabolism and maternal reproduction in recent years.
      Furthermore, there was a new function for p53 in antiviral apoptosis mentioned in
      the research, Integration of interferon-alpha/beta signaling to p53 responses in
      tumour suppression and antiviral defense. In order to define the antiviral
      function of p53, many target genes has been defined, such as IRF9, IRF5, ISG15
      and TLR3. All of these implied there must be a complex mechanism for role of p53
      in antiviral innate immunity, adaptive immunity and inflammation.

PMID- 22978175
TI  - [Regulation of NF-kappaB signaling pathway by poxvirus].
AB  - Poxviruses, a type of ds-DNA viruses which mainly target at the epithelial cell,
      are the pathogens of human and animals. During the revolution of poxviruses, the
      viruses encode multiple proteins that regulate the immune system to monitor the
      viral reproductive cycle in host cells. The nuclear kappa B (NF-kappaB) pathway
      is essential to signal transcription in the innate immune system. Therefore,
      poxviruses have adopted different strategies to elude immune detection and
      destruction regulated by NF-kappaB. Further research in this field would help us
      develop preventive and therapeutic preparation for pox. Given the renewed
      interest in poxvirus, we review the current understanding of how the various
      classes of poxviralimmunomodulatory proteins target and manipulate the NF-kappaB
      pathway.

PMID- 22978176
TI  - [Research progress of the anti-HIV activity of SAMHD1].
AB  - The SAM and HD domain containing protein 1 (Sterile alpha motif domain and HD
      domain-containing protein 1, SAMHD1) is a putative negative regulator of the
      antiviral innate immune response. It can significantly increase the antiviral
      immune response, mediates the interferon-induced inflammatory response involved
      in the host foreign-virus defense system. The early studies have focused on its
      gene mutations associated with Aicardi-Goutieres syndrome (AGS), the latest study
      found that SAMHD1 as a potent dGTP-stimulated triphosphohydrolase restricts HIV-1
      replication by hydrolyzing the majority of cellular dNTPs, thus inhibiting
      reverse transcription and viral complementary DNA (cDNA) synthesis. Auxiliary
      gene of HIV-2 and simian immunodeficiency virus (SIVsm / mac) encoding the Vpx
      protein can eliminate HIV-1 restriction. In recent years, the research on SAMHD1,
      mores forward rapidly this paper overviews the recent research progression
      related to the above fields.

PMID- 22978177
TI  - [Reseanh advance in human astrovirus].
AB  - Human astroviruses have been recognized as one of the important causes of viral
      gastroenteritis in infants and young children. In the present work, we reviewed
      the progress of astrovirus infections in humans, focusing on the serotypes
      molecular biological, characteristics of disease, pathogenic mechanism,
      epidemiology and detection methods, and concluded that there were multiple
      astroviruses circulating in the world, and several novel astroviruses were
      discovered in recent years. Human astrovirus 1 was the most prevailing serotype.
      Which caused intestinal and parenteral infections, and the characteristics of
      infections were similar to other diarrheal viruses. However, the pathogenic
      mechanism remained unknown. Only limited data was available about the correlation
      between the novel astroviruses and diseases, and the laboratory detection methods
      needed to be established.

PMID- 22978178
TI  - Chiasmal optic neuritis in a 4-year-old girl: a case report and review of the
      literature.
AB  - We report a 4-year-old girl presenting with sudden severe bilateral visual loss.
      Ophthalmological examination revealed optic disc pallor. Further neurological
      examination was normal. Brain magnetic resonance imaging (MRI) suggested chiasmal
      optic neuritis, and further etiological investigations were negative. We review
      the literature on the incidence and underlying etiology of chiasmal optic
      neuritis in childhood.

PMID- 22978179
TI  - [Optical coherence tomography in Sjogren-Larsson Syndrome diagnosis].
AB  - PURPOSE: To study the clinical and the optical coherence tomography (OCT)
      features of crystalline_macular dystrophy in a 14-year-old man with Sjogren
      Larsson syndrome (SLS). CASE REPORT: A 14-year-old man was hospitalized because
      of a severe hyperkeratosis, epilepsy, spastic paraplegia and mental retardation.
      The diagnosis of SLS was considered. A bilateral crystalline maculopathy was
      detected by fundus ophthalmoscopy. OCT showed bilateral focal perifoveal
      hyperreflectivities and microcystoid spaces. DISCUSSION-CONCLUSION: OCT features
      of the crystalline maculopathy could point at SLS in undiagnosed patients. It is
      a low cost and non invasive procedure that could be of value in elucidating the
      pathophysiological mechanisms of SLS.

PMID- 22978180
TI  - [Congenital corneal anesthesia. A case report].
AB  - Congenital corneal anesthesia (CCA) is an uncommon condition difficult to
      diagnose. We report the case of a 4-year-old girl who presented with bilateral
      congenital corneal anesthesia revealed by a corneal ulcer which had been
      unresponsive to adapted local treatment. Self-inflicted corneal injuries were
      present. It is important to search for corneal anesthesia in children with
      chronic ulceration of the cornea and selfinflicted injuries.

PMID- 22978181
TI  - [Unilateral panuveitis following intravesical therapy with bacille of Calmette et
      Guerin].
AB  - Uveitis occuring after Mycobacterium bovis-bacille Calmette-Guerin (BCG)
      intravesical therapy for bladder carcinoma is rare. Only a few cases have been
      described. Its physiopathology is still unknown. Two mechanisms can be proposed
      at the origin of ocular inflammation: a local immune response or a direct
      choroidal mycobacterial infection as demonstrated by vitreous cultures. We report
      the case of 63-year-old man who presented with unilateral panuveitis after the
      fifth BCG intravesical instillation with no other systemic manifestations. There
      was no evidence for any other etiology for this uveitis. Loss of light perception
      occurred despite systemic antimycobacterial therapy and systemic prednisone
      therapy because of delayed diagnosis. This outlines the absolute need for a close
      ophthalmological monitoring of patients receiving a BCG therapy to allow an
      earlier diagnosis of this complication and appropriate treatment.

PMID- 22978182
TI  - [Keratouveitis and lens opacity caused by butterfly hair].
AB  - Butterfly hair is known to cause eye injury. In Africa, incriminated butterflies
      are Hylesia (spp). We report a case of a sub-epithelial keratitis associated with
      anterior uveitis following a trauma by a butterfly that was complicated by late
      lens opacity due to butterfly hair. Ocular lesions caused by butterfly hair are
      rare, but require an urgent management to prevent late and severe complications
      due to intraocular migration of the hairs.

PMID- 22978184
TI  - Myelinated retinal nerve fibers, high myopia and amblyopia: a clinical entity.

PMID- 22978183
TI  - The effect of phacoemulsification and combined phaco/glaucoma procedures on the
      intraocular pressure in open-angle glaucoma. A review of the literature.
AB  - PURPOSE: This review article addresses the different aspects that influence the
      choice and sequence of surgical treatment in patients with coexisting open-angle
      glaucoma and cataract. The effect of phacoemulsification on the intraocular
      pressure (lOP) and on a preexisting bleb is discussed and phacotrabeculectomy and
      trabeculectomy are compared. Moreover, the most recent surgical pressure lowering
      techniques in combination with phacoemulsification are reviewed: iStent,
      Trabectome, Hydrus, Cypass and Canaloplasty. METHODS: Medline database was used
      to search for relevant, recent articles. CONCLUSION: A sustained IOP decrease of
      1.5 mmHg can be expected after a phacoemulsification in patients with open-angle
      glaucoma. The higher the preoperative pressure, the greater the IOP lowering will
      be. A phacoemulsification on a trabeculectomized eye will often lead to reduced
      bleb function and an IOP rise of on average 2 mmHg after 12 months. Compared to a
      trabeculectomy, phaco-trabeculectomy will have a less IOP lowering effect and a
      higher complication rate. iStent and Trabectome combined with phacoemulsification
      can decrease the IOP with 3 to 5mmHg, with a low complication rate. The
      combination of Cypass and Hydrus with phaco-surgery may have a more significant
      IOP lowering effect but long term results are not yet published. Combining
      Canaloplasty with phacoemulsification is a more challenging surgery but if a
      tension suture can be placed, an IOP decrease around 10 mmHg might be expected.

PMID- 22978185
TI  - The relationship between running economy and biomechanical variables in distance
      runners.
AB  - In this study, we analyzed the relationship between running economy (RE) and
      biomechanical parameters in a group running at the same relative intensity and
      same absolute velocity. Sixteen homogeneous male long-distance runners performed
      a test to determine RE at 4.4 m.s(-1), corresponding to 11.1% below velocity at
      the ventilatory threshold. We found significant correlations between RE and
      biomechanical variables (vertical oscillation of the center of mass, stride
      frequency, stride length, balance time, relative stride length, range of elbow
      motion, internal knee, ankle angles at foot strike, and electromyographic
      activity of the semitendinosus and rectus femoris muscles). In conclusion,
      changes in running technique can influence RE and lead to improved running
      performance.

PMID- 22978186
TI  - Differences in the intensity and duration of adolescents' sports and exercise
      across physical and social environments.
AB  - We used data from the American Time Use Survey (years 2003-06) to analyze whether
      the intensity and duration of high school students' (ages 15-18 years) sports and
      exercise bouts differed across physical and social environments. Boys' sports and
      exercise bouts were more likely to reach a vigorous intensity when taking place
      at school and with friends/acquaintances/other people; whereas girls' sports and
      exercise bouts were more likely to reach a vigorous intensity when outdoors and
      alone. For boys and girls, bout durations were greater at school and with
      friends/acquaintances/other people than in other environments. Overall,
      environmental influences on the intensity but not duration of sports and exercise
      bouts appear to differ between boys and girls.

PMID- 22978187
TI  - The reliability of classification decisions for the Furtado-Gallagher
      Computerized Observational Movement Pattern Assessment System--FG-COMPASS.
AB  - Mastery of fundamental movement skills (FMS) is an important factor in preventing
      weight gain and increasing physical activity. To master FMS, performance
      evaluation is necessary. In this study, we investigated the reliability of a new
      observational assessment tool. In Phase I, 110 video clips of children performing
      five locomotor, and six manipulative FMSs were developed. In Phase II, rating
      scales were developed, and their efficacy was evaluated by comparing judgments of
      30 undergraduate students to a standard. The mean weighted kappa (.71) was
      considered good (range .51-.85). Of the 11 rating scales, 6 were modified, and 5
      remained unchanged. This study sets the foundation for the development of a new
      observational scale to assess fundamental movement skills.

PMID- 22978188
TI  - Influence of weight classification on walking and jogging energy expenditure
      prediction in women.
AB  - The purpose of this study was to determine the influence of weight classification
      on predicting energy expenditure (EE) in women. Twelve overweight (body mass
      index [BMI] = 25-29.99 kg/m(2)) and 12 normal-weight (BMI = 18.5-24.99 kg/m(2))
      women walked and jogged 1,609 m at 1.34 ms(-1) and 2.23 ms(-1), respectively,
      while EE was assessed using indirect calorimetry and compared to several other
      prediction methods (American College of Sports Medicine [ACSM], 2010; Heyward,
      2006; Leger & Mercier, 1984; McArdle, Katch, & Katch, 2006; Pandolf Givoni, &
      Goldman, 1978; van der Walt & Wyndham, 1973). More error occurred with overweight
      EE prediction compared to normal-weight EE prediction. The ACSM and Heyward
      methods for walking and the McArdle et al. method for jogging most accurately
      predicted EE for both groups. Weight classification influences EE prediction
      accuracy and, thus, is important to consider when using these prediction methods.

PMID- 22978189
TI  - Does computer-based motor skill assessment training transfer to live assessing?
AB  - Developing competency in motor skill assessment has been identified as a critical
      need in physical educator preparation. We conducted this study to evaluate (a)
      the effectiveness of a web-based instructional program --Motor Skill Assessment
      Program (MSAP)-- for developing assessment competency, and specifically (b)
      whether competency developed by using this method transferred to participants'
      ability to accurately assess actual students in a gymnasium setting. Participants
      were 36 (9 men and 27 women) preservice kinesiology majors. Results revealed they
      performed significantly better on assessing a motor skill after using MSAP
      training and this training transferred to significant improvements in accurately
      assessing students in an actual gymnasium setting

PMID- 22978190
TI  - Effect of ball mass on dribble, pass, and pass reception in 9-11-year-old boys'
      basketball.
AB  - The objective of the study was to analyze the effect of ball mass on dribble,
      pass, and pass reception in real game situations in 9-11-year-old boys'
      basketball. Participants were 54 boys identified from six federated teams. The
      independent variable was ball mass, and dependent variables were number of
      dribbles, passes, and pass receptions. Three situations were established in which
      the participants played four games with each of the following: (a) regulation
      ball (485 g, 69-71 cm), (b) ball of smaller mass (440 g, 69-71 cm), and (c) ball
      of greater mass (540 g, 69-71 cm). Four observers recorded data from observing
      game videos using a computerized register instrument. Participants executed more
      dribbles, passes, and pass receptions with the 440g ball when compared to the
      regulation (p < .05) and 540g ball (p < .01). Reduction of ball mass seems to
      have enabled the children to go from paying attention to aspects related to ball
      handling to aspects of game interpretation.

PMID- 22978191
TI  - A model for the transfer of perceptual-motor skill learning in human behaviors.
AB  - This paper presents a preliminary model that outlines the mechanisms underlying
      the transfer of perceptual-motor skill learning in sport and everyday tasks.
      Perceptual-motor behavior is motivated by performance demands and evolves over
      time to increase the probability of success through adaptation. Performance
      demands at the time of an event create a unique transfer domain that specifies a
      range of potentially successful actions. Transfer comprises anticipatory
      subconscious and conscious mechanisms. The model also outlines how transfer
      occurs across a continuum, which depends on the individual's expertise and
      contextual variables occurring at the incidence of transfer

PMID- 22978192
TI  - The relationship of actigraph accelerometer cut-points for estimating physical
      activity with selected health outcomes: results from NHANES 2003-06.
AB  - The purpose of this study was to examine the influence of child and adult cut
      points on physical activity (PA) intensity, the prevalence of meeting PA
      guidelines, and association with selected health outcomes. Participants (6,578
      adults > or = 18 years, and 3,174 children and adolescents < or = 17 years) from
      the National Health and Nutrition Examination Survey 2003-06 (Centers for Disease
      Control and Prevention, 2006) wore an accelerometer for 7 days. PA intensity was
      estimated with 5 child-derived and 12 adult-derived cut-points. For all, the cut
      point influenced PA intensity and the prevalence of meeting PA guidelines.
      Similarly, cut-point selection influenced the relationship between physical
      activity and various health outcomes. Future research should further enhance
      meaningful cut-points relevant to populations with diverse health and age
      profiles.

PMID- 22978193
TI  - Social connection and psychological outcomes in a physical activity-based youth
      development setting.
AB  - It is believed that the social connections formed by participating in physical
      activity-based positive youth development (PYD) programs contributes to building
      personal and social assets. In this study, we examined how changes in social
      connection over a physical activity-based PYD program for low-income youth were
      associated with changes in psychological outcomes. Participants (N = 197)
      completed pre- and postprogram questionnaires assessing leader support, social
      competence, physical competence, and psychological outcomes (global self-worth,
      physical self-worth, attraction to physical activity, and hope). Social
      competence, physical competence, physical self-worth, and global self-worth
      increased significantly over the 4-week program. Changes in social connections
      predicted changes in psychological outcomes. Effect sizes were modest but suggest
      that social interventions hold potential to promote positive outcomes in
      underserved youth.

PMID- 22978194
TI  - Selective influence of circadian modulation and task characteristics on motor
      imagery time.
AB  - In this study, we examined the effect of circadian modulation on motor imagery
      (MI) time while also considering the effects of task complexity and duration. The
      ability to imagine in real time was influenced by circadian modulation in a
      simple walking condition, with longer MI times in the morning and evening
      sessions. By contrast, there was no effect of circadian rhythm in the complex,
      short or long walking conditions. We concluded that motor imagery time is
      modulated during the course of the day, but the effect of task difficulty is
      stronger than circadian modulation in altering the temporal congruence between
      physical practice and MI performance. Practical applications in motor learning
      and rehabilitation are discussed.

PMID- 22978195
TI  - Women's health-enhancing physical activity and eudaimonic well being.
AB  - In this study, we explored the role of health-enhancing physical activity (HEPA;
      Miilunpalo, 2001) in women's eudaimonic well being (i.e., psychological
      flourishing at one's maximal potential; Ryff 1989). We used a quantitative
      approach (N= 349) to explore the relationship between HEPA and eudaimonic well
      being. While HEPA was not related to eudaimonic well being, experiencing
      eudaimonia through HEPA contributed unique variance in eudaimonic well being
      beyond HEPA and experiencing hedonia through HEPA. As quality of activity was
      more important than quantity, a qualitative component (N = 10) provided further
      insight on if and how HEPA contributes to women's eudaimonic well being.
      Participants supported HEPA in fulfilling their potential through goal
      setting/striving providing bonding experiences, allowing for self-reflection, and
      developing a physical/able body.

PMID- 22978196
TI  - Training visual control in wheelchair basketball shooting.
AB  - We examined the effects of visual control training on expert wheelchair
      basketball shooting, a skill more difficult than in regular basketball, as
      players shoot from a seated position to the same rim height. The training
      consisted of shooting with a visual constraint that forced participants to use
      target information as late as possible. Participants drove under a large screen
      that initially blocked the basket. As soon as they saw the basket they shot. When
      training with the screen, shooting percentages increased. We conclude that visual
      control training is an effective method to improve wheelchair basketball
      shooting. The findings support the idea that perceptual-motor learning can be
      enhanced by manipulating relevant constraints in the training environment, even
      for expert athletes.

PMID- 22978197
TI  - Checking in: an analysis of the (lack of) body checking in women's ice hockey.
AB  - Despite the growing popularity of women's ice hockey in North America, players
      continue to face limitations because of the prohibition of body checking. In this
      paper we argue from a liberal feminist philosophical perspective that this
      prohibition reinforces existing traditional stereotypes of female athletes.
      Because the women's game does not incorporate checking, female ice hockey players
      are not afforded the same opportunity to flourish as men and experience bodily
      agency, which results in continued male domination of the game, therefore,
      indirectly reinforcing a gender hierarchy in hockey and society.

PMID- 22978198
TI  - Implicit and explicit exercise and sedentary identity.
AB  - We examined the relationship between implicit and explicit "exerciser" and
      "sedentary" self-identity when activated by stereotypes. Undergraduate
      participants (N = 141) wrote essays about university students who either liked to
      exercise or engage in sedentary activities. This was followed by an implicit
      identity task and an explicit measure of exercise self-identity. Results showed
      that implicit and explicit exerciser identities were not highly correlated. There
      were also no significant prime effects, but women showed greater implicit
      sedentary identity, whereas men showed greater implicit exercise identity. This
      research suggests that implicit exercise-related identity is a distinct construct
      from explicit exercise identity. The results also reflect responses to societal
      pressures for women to be thin and for men to be strong, when free of self
      presentational bias.

PMID- 22978199
TI  - A little bit of this and a little bit of that: an update.

PMID- 22978200
TI  - Representativeness in studies of early cochlear implantation.

PMID- 22978201
TI  - Characteristics of a virtual community for individuals who are d/deaf and hard of
      hearing.
AB  - The content of 2,050 messages on a virtual forum for d/Deaf and hard of hearing
      people in Israel was analyzed. Interactions and behavior were monitored to
      determine if behavior on the forum expressed social support, and whether the
      community was an entirely virtual community or a real community whose members
      also met in other venues. Subjects discussed in messages included technical
      difficulties, coping with difficulties presented by hearing loss, adjusting to
      assistive devices, difficulties at school and work, accessibility issues,
      difficulties communicating with the hearing world, and rights. Messages were also
      used to initiate a range of social activities. Classification of behaviors per
      the Social Support Behavior Code (Cutrona & Suhr, 1992) showed that most were in
      the category of informational support. Other types of support in the model,
      tangible assistance, emotional support, social network support, and esteem
      support, were evident in fewer messages.

PMID- 22978202
TI  - Education, employment, and independent living of young adults who are deaf and
      hard of hearing.
AB  - Little information is available on the education, employment, and independent
      living status of young deaf and hard of hearing adults who have transitioned from
      high school. The present article reports postsecondary outcomes of 46 young
      adults who had attended for at least 4 years a non-public agency school in the
      northwestern United States specializing in deaf education. School administrators
      had developed a specific philosophy and operationalized it in an academic and
      literacy-based curriculum incorporating a grammatically accurate signing system.
      The researchers found that most or all participants had finished high school, had
      earned a college degree, were employed, and were living independently. Findings
      are discussed in terms of the available literature and the study's contribution
      to a limited body of recent research on young postsecondary deaf and hard of
      hearing adults.

PMID- 22978203
TI  - Fathers' involvement in preschool programs for children with and without hearing
      loss.
AB  - The authors compared the involvement in children's development and education of
      38 fathers of preschoolers with hearing loss to the involvement of a matched
      group of 36 fathers of preschoolers with normal hearing, examining correlations
      between child, father, and family characteristics. Fathers completed self-reports
      regarding their parental involvement and parenting self-efficacy and reported on
      their family cohesion and adaptability. Mothers also reported on their husbands'
      involvement. Similarly high levels of involvement on the part of both groups of
      fathers were found. Involvement correlated positively with fathers' self-reported
      parenting self-efficacy, family cohesion, and adaptability, and mother-reported
      paternal involvement. Implications for professionals and mothers are discussed,
      including the need to encourage mothers' support for their husbands' involvement
      and to empower fathers' sense of competency in order to increase their
      involvement.

PMID- 22978204
TI  - A comparison of phonological processing skills of children with mild to moderate
      sensorineural hearing loss and children with dyslexia.
AB  - Using the comprehensive Test of Phonological Processes (Wagner, Torgesen, &
      Rashotte, 1999), the researchers compared strengths and weaknesses in
      phonological processing skills in three groups: 21 children with mild to moderate
      sensorineural hearing loss (MSNH group), 29 children with dyslexia, and 30 age
      matched controls. The MSNH group showed phonological deficits that were
      restricted to phonological awareness tasks (elision/blending) and a phonological
      memory task (nonword repetition), yet exhibited unimpaired rapid naming ability.
      Children with dyslexia showed deficits in all 3 phonological constructs. Finally,
      both degree of hearing loss and age at which hearing loss was identified in the
      MSNH group were related to the children's phonological processing skills. Because
      of their deteriorated phonological skills, children with MSNH may be at risk of
      starting school with weaknesses in early literacy skills. Implications for
      practice aimed at improving phonological and literacy skills of these children
      are described.

PMID- 22978205
TI  - Reading to deaf children who sign: a response to Williams (2012) and suggestions
      for future research.
AB  - A commentary on Williams's (2012) invited article on the use of adapted
      vocabulary learning interventions focuses on three areas: (a) Vocabulary
      interventions with storybook reading originally designed for hearing children can
      be adapted for deaf children. (b) Teachers are invited to reflect on how the read
      aloud process in English differs from the read-aloud process in sign. (b)
      Teachers are asked to consider adding drawing and writing activities to reading
      lessons to show young deaf readers how reading and writing are reciprocal
      processes. The emergent literacy theory is used, as it informs and drives
      instructional vocabulary teaching practices for deaf children in preschool,
      kindergarten, and first grade. The emergent literacy theory broadly captures
      cognitive, social, perceptual, and linguistic understandings of how young signing
      deaf children acquire both English word recognition abilities and vocabulary
      knowledge, among other important prereading concepts.

PMID- 22978206
TI  - Terpenoids from Cichorium intybus.
AB  - A new sesquiterpenoid, 1alpha,5alpha-epoxy-4alpha-hydroxyl-4beta,10beta-dimethyl
      7alphaH,10alphaH-guaia-l1(13)-en-12-oic acid (1), and four known compounds,
      lactucin (2), 1beta-hydroxy-7alphaH,8,11betaH-eudesm-3-en-8,12-olide (3), 13,14
      seco-stigma 9(11),14(15)-dien-3alpha-ol (4), and bacosterol-3-O-beta-D
      glucopyranoside (5) were isolated from Cichorium intybus L. Their structures were
      determined on the basis of detailed analysis of their 1D- and 2D-NMR
      spectroscopic and mass spectrometric data. Compounds 2 and 4 showed strong
      activities against the A2780 cell line with IC50 values of 1.81 and 0.07 microM,
      respectively.

PMID- 22978208
TI  - The cytotoxic activity of diterpenoids from Isodon species.
AB  - Fifteen Isodon diterpenoids (1-15) were evaluated for their cytotoxic activity
      against HeLa and HL-60 human cancer cell lines, and against murine vincristine
      (VCR)-resistant P388 cells. Kamebanin (14) showed efficient cytotoxic activity
      against HeLa and HL-60 cells. In addition, although dihydroenmein (2) and
      trichorabdal B (7) were inactive against several tested cell types, they were
      found to have cytotoxic-enhancing activity of VCR against VCR-resistant P388
      cells.

PMID- 22978207
TI  - (6R,9S)-6"-(4"-hydroxybenzoyl)-roseoside, a new megastigmane derivative from
      Ouratea polyantha and its effect on hepatic glucose-6-phosphatase.
AB  - A new megastigmane derivative, (6R,9S)-6'-(4"-hydroxybenzoyl)-roseoside (1) and
      two known compounds, the biflavoneagathisflavone (2) and 4-hydroxybenzoic acid
      (3) were isolated and purified from leaves and stems of Ouratea polyantha Engl.
      Agathisflavone was isolated in a single high-speed countercurrent chromatography
      run, while the megastigmane was purified in two steps, by using a combination of
      high-speed countercurrent chromatography and analytical column chromatography.
      All structures were elucidated on the basis of spectral evidence and comparison
      with literature data. Compound 1 was characterized by [alpha]D20, UV-Vis, IR, MS,
      1H NMR, 13C NMR, HMQC, HMBC, COSY and NOESY. Compounds 1 and 2 showed an
      inhibitory effect of 63.6 and 13.7% on the G-6-Pase intact microsomes,
      respectively.

PMID- 22978209
TI  - Anti-proliferative activity and apoptotic potential of britannin, a sesquiterpene
      lactone from Inula aucheriana.
AB  - Inula aucheriana n-hexane, CHCl3 and MeOH extracts were evaluated for their anti
      proliferative activity against HepG-2, MCF-7, MDBK and A-549 cells. The CHCl3
      extract exhibited cytotoxic activity to the above cell lines with IC50 values of
      13.5, 23.4, 10.5, and 26.9 microg/mL, respectively. The sesquiterpene lactone
      britannin was isolated from the above extract. This was further evaluated in the
      MTT assay to demonstrate strong cytotoxicity to the mentioned cell lines (IC50:
      2.2, 5.9, 5.4, and 3.5 microg/mL, respectively), and the apoptotic inducing
      properties of britannin were evaluated on human breast adenocarcinoma (MCF-7)
      cells through the terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assay.

PMID- 22978210
TI  - Betulin as an antitumor agent tested in vitro on A431, HeLa and MCF7, and as an
      angiogenic inhibitor in vivo in the CAM assay.
AB  - Betulin, an important compound found in birch tree bark, can be converted to
      betulinic acid, an important pharmacological substance. Betulin has recently been
      reported as a cytotoxic agent for several tumor cell lines and as an apoptotic
      inductor. Angiogenesis is a key process involved in tumor metastasis and in
      developing tumor resistance to cytotoxic therapy. There are little data on
      betulin as an anti angiogenic agent. This preliminary study aimed to evaluate the
      cytotoxic effect of betulin on three cancer cell lines: HeLa (cervix
      adenocarcinoma), MCF7 (breast adenocarcinoma) and A431 (skin epidermoid
      carcinoma), and the apoptotic mechanism, as well as the implication in the
      capillary formation of the chicken embryo chorioallantoic membrane. The analysis
      consisted in the interpretation of the MTT assay and fluorescence double staining
      with Hoechst dye 33258 and propidium iodide, while the angiogenic effect was
      evaluated using morphological and immunohistochemical techniques. The antitumor
      activity is revealed by the double fluorescence staining, indicating that at
      higher concentrations, the cell membrane permeability is enhanced, while at lower
      concentrations there is evidence for nuclear fragmentation. In what concerns its
      effect on the process of blood vessel formation, betulin induced the reduction of
      newly formed capillaries, especially in the mesenchyme, possible through
      targeting the normal function of endothelial cells. In vitro results proved the
      superior specificity of betulin on cervical cancer cells, followed by skin cancer
      cells.

PMID- 22978211
TI  - Constituents of twig bark of pear cultivars (Pyrus species).
AB  - Organic solvent extracts from fresh twig bark of Japanese pear cultivars (Pyrus
      serotina) Shinko and Nijisseiki, and European pear cultivar (P. communis) Le
      Lectier were obtained by maceration with n-hexane and EtOAc, and analyzed in GC
      EIMS experiments. In these two Japanese cultivars, the lupeol, betulin,
      epifriedelinol, friedelin and arbutin contents of Nijisseiki were higher than
      those of Shinko. In the case of the lupane-type triterpenes, lupeol and betulin,
      the lupeol content of Japanese pears Shinko and Nijisseiki was higher than that
      of European pear Le Lectier. The betulin content of Le Lectier was higher than
      those of Shinko and Nijisseiki. Friedelane-type triterpenes, epifriedelinol and
      friedelin, were not detected in twig bark of Le Lectier. Quantitative and
      qualitative differences in the constituents of these three pear cultivars were
      observed.

PMID- 22978212
TI  - Bio-assay guided isolation of alpha-glucosidase inhibitory constituents from
      Eclipta alba.
AB  - Eclipta alba (L.) Hassk is used traditionally in diabetes mellitus in India and
      the plant extract is reported to possess anti-diabetic activity. A bioactivity
      guided isolation approach based on alpha-glucosidase inhibition was used to
      identify the constituents contributing towards the inhibition of the enzyme and
      probably contributing towards its anti-diabetic activity. Four echinocystic acid
      glycosides were thus isolated, of which eclalbasaponin VI, isolated from the n
      butanol fraction, was found to be the most potent (IC50 54.2 +/- 1.3 microM). The
      compound is an uncompetitive type of inhibitor with Ki 26.1 microM. A
      quantitative estimation of the constituents was established using RP-HPLC.

PMID- 22978213
TI  - Chromolithic method development, validation and system suitability analysis of
      ultra-sound assisted extraction of glycyrrhizic acid and glycyrrhetinic acid from
      Glycyrrhiza glabra.
AB  - An ultrasound-assisted extraction and chromolithic LC method was developed for
      simultaneous determination of glycyrrhizic acid (GA) and glycyrrhetinic acid (GL)
      from the root extract of Glycyrrhizza glabra using RPLC-PDA. The developed method
      was validated according to the International Conference on Harmonisation. The
      method exhibited good linearity (r2 > 0.9989) with high precision and achieved
      good accuracies between 97.5 to 101.3% of quantitative results. The method is
      more sensitive and faster (resolved within ten minutes) than the earlier
      developed methods using normal LC columns.

PMID- 22978214
TI  - Furostanol saponin and diphenylpentendiol from the roots of Asparagus racemosus.
AB  - A new furostanol steroidal saponin, shatavaroside C (1), and a new
      diphenylpentendiol, shatavarol (2), together with five known compounds,
      shatavarin IV (3), racemoside A (4), beta-sitosterol (5) stigmasterol (6) and
      ursolic acid (7), have been isolated from the roots of Asparagus racemosus. This
      is the first report on the isolation of racemoside A (4) from roots of the plant.
      Structures of isolated compounds were determined on the basis of detailed
      analysis of their 1D, 2D NMR and mass spectral data.

PMID- 22978215
TI  - Quinolizidine alkaloids from Sophora velutina subsp. zimbabweensis (Fabaceae:
      Sophoreae).
AB  - Three novel quinolizidine alkaloids, N-methylenehydroxycytisine (1), 6,7
      dihydroxylupanine (2), and velutinine (3) have been isolated from the fruits and
      pods (1 and 2) and stem bark (3) of Sophora velutina subsp. zimbabweensis along
      with the known quinolizidine alkaloids, 7-hydroxylupanine (4), thermopsine (5), N
      methylcytisine (6), cytisine (7), an aromatic ester, methyl-3-(3',4'
      dimethoxyphenyl)-2-propenoate (8) and the triterpenoids, lup-20(29)-ene-3beta-ol
      (9) and 12-oleanen-3-one (10). Compounds 6 and 10 showed good antibacterial
      activity against E. faecalis, with MIC values of 20.8 and 10.9 microg mL(-1),
      respectively. The other compounds tested exhibited low to moderate antibacterial
      activity.

PMID- 22978216
TI  - Flavonoids from the Japanese monotypic genus, Nipponanthemum.
AB  - Foliar flavonoids of Nipponanthemum, which is a monotypic genus and consists of
      only one Japanese endemic species, N. nipponicum, were isolated for the first
      time. Fifteen flavonoids, i.e. six glycosides, quercetin 3,7-di-O-glucoside,
      vicenin-2, quercetin 3-O-glucoside, luteolin 7-O-glucoside, kaempferol 3-O
      glucoside and apigenin 7-O-glucoside, and nine aglycones, luteolin, nepetin,
      quercetin 3-methyl ether, axillarin, apigenin, hispidulin, chrysoeriol,
      jaceosidin and sudachitin were identified. Of these compounds, the flavonoid
      aglycones existed on the leaf surface.

PMID- 22978217
TI  - The inhibitory effects of representative chalcones contained in Angelica keiskei
      on melanin biosynthesis in B16 melanoma cells.
AB  - In our effort to find new whitening agents, we evaluated the effects of
      representative chalcones [4-hydroxyderricin (1), xanthoangelol (2), xanthoangelol
      H (3), deoxyxanthoangelol H (4), and deoxydihydroxanthoangelol H (5)] contained
      in the stem of Angelica keiskei on tyrosinase and melanin formation in B16
      melanoma cells. In addition, the antioxidant effects of these chalcones in ORAC
      and DPPH assays were also determined. Interestingly, all chalcones (1-5) inhibit
      melanin formation in B16 melanoma cells, with low cytotoxicity.

PMID- 22978218
TI  - Flavonoid constituents of Pistacia integerrima.
AB  - Pistacides A and B (1-2), two new flavonoid glycosides, have been isolated from
      the methanolic extract of the aerial parts of Pistacia integerrima, along with 2'
      hydroxyisoorientin (3), echioidinin 2'-O-beta-D-(6"-O-acetyl) glucopyranoside
      (4), chrysoeriol (5), and diandraflavone A (6), reported for the first time from
      this species. Their structures were elucidated by spectroscopic analysis
      including 2D NMR, FAB-MS, and acidic hydrolysis.

PMID- 22978219
TI  - Antioxidant and anti-cholinesterase activity of Globularia meridionalis extracts
      and isolated constituents.
AB  - The antioxidant and anti-cholinesterase properties of Globularia meridionalis
      (Podp.) O. Schwarz (Globulariaceae) were investigated. G. meridionalis aerial
      parts and roots were extracted with methanol, and the total extract successively
      partitioned with n-hexane. The methanol fraction of the roots showed the highest
      antioxidant activity with IC50 values of 8.0 and 2.1 microg/mL in the DPPH and
      beta-carotene bleaching tests, respectively. From this fraction, three
      flavonoids, namely pectolinarigenin 7-O-beta-glucoside, apigenin 7-O-beta
      glucoside and luteolin, and two phenylethanoids, namely acteoside and
      isoacteoside, were isolated. Potential anti-cholinesterase effects were assessed
      through the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes
      inhibition assay. The n-hexane fraction of the roots exhibited the highest
      activity against both AChE and BChE with IC50 values of 65.5 and 70.4 microg/mL,
      respectively.

PMID- 22978220
TI  - Antioxidant activities and total phenolic and flavonoid contents in three
      indigenous medicinal vegetables of north-east India.
AB  - Antioxidant activities of the n-hexane, ethyl acetate and methanol extracts of
      three indigenous leafy vegetables of north east India viz., Polygonum
      microcephallum, Oxalis corniculata and Portulaca oleraceae were measured by
      spectroscopic methods using the 1, 1-diphenyl-2-picrylhydrazyl (DPPH*) radical
      assay and xanthine/xanthine oxidase assay. The total phenolic and total flavonoid
      contents of each extract were also measured to assess their effect on the
      antioxidant activity. It was observed that the methanol extracts of all the
      species showed the highest antioxidant activities and high values for total
      phenolic and flavonoid contents. A strong correlation between the antioxidant
      activities and the total phenolic content was observed for the three vegetables.
      It indicates that phenolics are one of the main components responsible for the
      antioxidant behavior of vegetables. HPLC analysis showed the presence of a number
      of identified phenolic compounds.

PMID- 22978221
TI  - In vitro antiviral activity of Heterophyllaea pustulata extracts.
AB  - The antiviral activity was tested of different polarity extracts, with differing
      chemical composition, obtained from aerial parts of Heterophyllaea pustulata Hook
      f. (Rubiaceae) against Herpes Simplex Virus Type I (HSV-1) and Saint Louis
      Encephalitis Virus (SLEV). The Vero cell line was employed as a host cell for the
      antiviral assessment of benzene (Ben), ethyl acetate (EtOAc) and ethanol (EtOH)
      extracts by means of the Neutral Red uptake assay and plaque reduction test. None
      of the extracts showed antiviral activity against SLEV. Only the extracts (Ben
      and EtOAc) with a high content of anthraquinones (AQs) inhibited HSV-1
      replication, exhibiting Selectivity Index (SI) values of 2.7 and 2.4,
      respectively. Therefore, these extracts could be good candidates as natural
      sources for antiviral drug development against HSV-1.

PMID- 22978222
TI  - Re-investigation of the anthraquinone pool of Rhamnus spp.: madagascin from the
      fruits of Rhamnus cathartica and R. intermedia.
AB  - As a continuation of our ongoing studies aimed at revealing the presence of
      oxyprenylated anthraquinones in plants belonging to the genus Rhamnus, in this
      paper we describe the extraction and HPLC separation of madagascin (3
      isopentenyloxyemodin) from the fruits of R. cathartica L. and R. intermedia
      Steud. and Hochst. The title compound is described herein for the first time as a
      component of fruit extracts of Rhamnus species.

PMID- 22978223
TI  - Two new phloroglucinol derivatives and five photosensitizing pheophorbides from
      Syzygium polyanthum leaves (Salam).
AB  - Two new phloroglucinol derivatives, identified as anthuminoate (1) and
      anthuminone (2), were isolated from the ichthyotoxic ethyl acetate fraction of
      Syzygium polyanthum leaves. In addition, bioassay-guided fractionation followed
      by dereplication of the photocytotoxic fraction of this plant part has resulted
      in the identification of five known pheophorbides as the bioactive constituents.
      The compounds were identified as pheophorbide-a, methyl pheophorbide-a, methyl
      hydroxypheophorbide-a, pheophorbide-b and hydroxypheophorbide-b. Inhibition of
      cell viability shown by the compounds ranged from 83.3 to 86.1% at a test
      concentration of 5 microg/mL. This shows that Syzygium polyanthum leaves are a
      potential new source in the studies of photocytotoxicity for photodynamic
      therapy.

PMID- 22978224
TI  - Production of Curcuminoids in different in vitro organs of Curcuma longa.
AB  - Curcuma longa L. (turmeric) is one of the most important spice and safe food
      additives. Its main constituents, curcuminoids, showed anti-inflammatory,
      antitumor and antioxidant effects. In the present work, an in vitro propagation
      method was developed to achieve selected plant organs with quantified curcuminoid
      content. In vitro plants were obtained from sprouting buds as primary explants.
      The major curcuminoid constituents, such as curcumin (CUR), demethoxycurcumin
      (DEM), and bis-demethoxycurcumin (bis-DEM) were examined in different organs by
      LC-DAD-ESI-MS. A significant production of curcumin (more than 260 microg g(-1)
      fresh weight) was obtained from in vitro microrhizomes, especially grown in a
      Murashige and Skoog medium (MS) supplemented with kinetin (0.1 mg L((-1)), alpha
      naphthaleneacetic acid (NAA, 1 mg L(-1)), sucrose (6%), agar (5%) and activated
      charcoal (0.1%). The analyzed microrhizomes showed reduced amounts of DEM and bis
      DEM in comparison with CUR levels. In addition a shoot culture line was suitable
      to biosynthesize curcuminoids, in a ratio very similar to that identified in the
      fresh rhizomes of parent plants. This study represents the first direct
      quantification of curcuminoids in turmeric in vitro shoots and microrhizomes to
      be used in dietary supplements.

PMID- 22978225
TI  - Two new alkylresorcinols from Homalomena wendlandii and their cytotoxic activity.
AB  - In the course of our search for antineoplasic agents from Panamanian Flora, two
      new alkylresorcinols: 1-(2,6-dihydroxyphenyl)octan-l-one (1) and (+)-1-(3-(1-(2,6
      dihydroxyphenyl)butyl)-2,6-dihydroxyphenyl)octan-l-one (2), together with three
      known compounds, (1R, 2R)-l-(benzo[d][1,3]dioxol-5-yl)propane-1,2,3-triol (3),
      (+)-aptosimon (4) and (-)-sesamin (5), were identified from the leaves of
      Homalomena wendlandii Schott (Araceae). Their structures were established by 1D
      and 2D NMR and IR spectroscopic, and MS methods. Compound 2 exhibited IC50 values
      of 3.3, 5.8 and 4.0 microg/mL against MCF-7, SF-268 and H-460 cancer human cell
      lines, respectively.

PMID- 22978226
TI  - Amides and an alkaloid from Portulaca oleracea.
AB  - A total of 16 phenolic compounds, including one new and five known N-cinnamoyl
      phenylethylamides, one new pyrrole alkaloid named portulacaldehyde, five
      phenylpropanoid acids and amides, and derivatives of benzaldehyde and benzoic
      acid, were isolated and identified from a polar fraction of an extract of
      Portulaca oleracea. Their structures were determined through spectroscopic
      analyses.

PMID- 22978227
TI  - Synthesis and biological evaluation of combretastatin A-4 and three
      combretastatin-based hybrids.
AB  - The syntheses of combretastatin A-4 from gallic acid and of three combretastatin
      based hybrids are described. Starting from commercial gallic acid, the
      phosphonium salt (3,4,5-trimethoxybenzylphosphonium bromide) is synthesized and
      coupled, through a Wittig reaction, with several aldehydes, including
      methoxymethyl-protected isovanillin, the aldehyde y-bicyclohomofarnesal having a
      labdane skeleton, 3-(3-pyridyl) propanal, and furfural. The biological properties
      of the cis-coupled compounds as cytotoxic, antiviral and antifungal agents are
      also reported. In addition, pyrogallol, gallic and 3,4,5-trimethoxybenzoic acids
      have been studied biologically.

PMID- 22978228
TI  - Two new p-terphenyl derivatives from the marine fungal strain Aspergillus sp.
      AF119.
AB  - Two new p-terphenyl derivatives (1, 2), together with six known ones (3-8), have
      been isolated from the marine fungal strain Aspergillus sp. AF119. The structures
      for terphyl acid (1) and terphyl diacid (2) were determined on the basis of HR Q
      TOF-MS, and 1D- and 2D-NMR spectroscopic data. The in vitro cytotoxic activities
      of compounds 1-8 were tested against human tumor cell lines HeLa, HepG-2 and MDA
      MB-435; only compounds 5-8 exhibited inhibitory activity against the tested cell
      lines with IC50 values < 20 microM. Moreover, compound 5 showed a mechanism of
      inducing cell cycle arrest and apoptosis mediated by the generation of ROS and
      subsequent DNA double-strand break.

PMID- 22978229
TI  - Quantitative analysis of fructo-oligosaccharides in Gynura divaricata subsp.
      formosana by high performance anion exchange chromatography-pulsed amperometric
      detection.
AB  - High performance anion exchange chromatography-pulsed amperometric detection was
      employed in this study to conduct quantitative analysis of the inulin-related
      fructo-oligosaccharides present in Gynura divaricata subsp. formosana. Result
      obtained for the 1-kestose (GF2), nystose (GF3) and 1F-beta-fructofuranosyl
      nystose (GF4) contents were 146.60 +/- 0.04, 24.70 +/- 0.75 and 16.60 +/- 0.91
      microg/g, fresh weight, and 68.90 +/- 0.02, 7.60 +/- 1.34 and 149.30 +/- 0.06
      microg/g (mean +/- RSD), dry weight, respectively. Using this method, the limit
      of quantitation was 20 microg/mL and the linear detectability between 0-250
      microg/mL. The developed method provides a practical analysis for these low
      caloric value, prebiotic and non-digestible carbohydrates in the genus Gynura.

PMID- 22978230
TI  - Polyketide metabolites from the endophytic fungus Microdiplodia sp. KS 75-1.
AB  - Through our screening for new natural compounds, four new polyketide metabolites,
      7,8-dihydonivefuranone A (1), 6(7)-dehydro-8-hydroxyterrefuranone (2), 8
      hydroxyterrefuranone (3), and 6-hydroxyterrefuranone (4) were isolated from the
      fermentation extract of Microdiplodia sp. KS 75-1, together with the known
      compounds nivefuranones A (5) and B (6); their structures were determined by
      spectroscopic (NMR, UV and IR) and MS analysis. Compounds 1, 2, 4 and 5 showed
      antimicrobial activity against Candida albicans and Staphylococcus aureus.

PMID- 22978231
TI  - Muscone exerts neuroprotection in an experimental model of stroke via inhibition
      of the fas pathway.
AB  - Identifying small molecules that are neuroprotective against stroke injury will
      be highly beneficial for treatment therapies. A cell viability assay and gas
      chromatography-mass spectrometry were used to identify active small molecules in
      XingNaoJing, which is a well known Chinese medicine prescribed for the effective
      treatment of stroke. Studies have found that muscone is the active compound that
      prevents PC12 cell and cortical neuron damage following various injuries.
      Analysis of apoptosis indicated that muscone inhibited glutamate-induced
      apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8
      expression were upregulated following glutamate treatment in cortical neurons,
      and was markedly attenuated in the presence of muscone. Furthermore, muscone
      significantly reduced cerebral infarct volume, neurological dysfunction and
      inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO)
      rats in a dose-dependent manner. Moreover, a significant decrease in Fas and
      caspase-8 expression in the rat cortex was observed in MCAO rats treated with
      muscone. Our results demonstrate that muscone may be a small active molecule with
      neuroprotective properties, and that inhibition of apoptosis and Fas is an
      important mechanism of neuroprotection by muscone. These findings suggest a
      potential therapeutic role for muscone in the treatment of stroke.

PMID- 22978232
TI  - Cytokinin and auxin effect on the terpenoid profile of the essential oil and
      morphological characteristics of shoot cultures of Artemisia alba.
AB  - The influence of plant growth regulators (PGR) on the essential oil composition
      and in vitro development of A. alba shoot cultures was studied. Two types of oils
      were determined, based on their terpenoid content. Close relations between the
      morphogenetic effects of PGR and the essential oil profile of the species were
      observed Predominance of root over shoot development was connected with a drop in
      the amounts of sesquiterpenoids and the direction of biosynthesis towards
      oxygenated monoterpenoids in the PGR-free control medium, as well in those with
      1.0 mg L(-1) indole-3-butyric acid (IBA) supplementation. On the contrary, lack
      of root formation and stimulated callusogenesis caused by the addition of 0.2 mg
      L(-1) 6-benzyladenine (BA), irrespectively of the presence of IBA (either 0.5 mg
      L(-1) or 1.0 mg L(-1)), resulted in the strong prevalence of sesquiterpenoids in
      the oils. These results are indicative that the morphological development ofA.
      alba shoot cultures affects the terpenoid biosynthetic pathway bringing out the
      hypothesis for a possible root to shoot signaling.

PMID- 22978233
TI  - Variation in the volatile constituents of different plant parts of Ligusticopsis
      wallichiana from western Himalaya, India.
AB  - The essential oil composition of the leaves, stem, flowers and roots of
      Ligusticopsis wallichiana (DC.) Pimenov & Kljuykov were analyzed by GC-FID and GC
      MS methods. Forty-five constituents, forming 93.2%-97.8% of the oil compositions,
      were dominated by acetylenic (31.5%-92.8%) compounds and sesquiterpenoids (0.3%
      44.4%). The leaf essential oil was mainly composed 3,5-nonadiyne (35.8%), beta
      selinene (20.9%), alpha-funebrene (10.1%) and (Z)-falcarinol (6.1%). The stem oil
      was dominated by acetylenic compounds (73.8%) represented by 3,5-nonadiyne
      (67.8%) and (Z)-falcarinol (5.7%). On the contrary, the major components of the
      flower essential oil were sesquiterpenoids (37.5%), such as germacrene D (16.6%),
      alpha-funebrene (7.4%), and acetylenic compounds (31.5%), such as (Z)-falcarinol
      (21.0%) and 3,5-nonadiyne (10.0%). Monoterpenoids constituted 23.9% of the flower
      oil with limonene (19.9%) as the single major constituent. The essential oil of
      the roots was dominated by 3,5-nonadiyne (90.5%). The results showed considerable
      qualitative and quantitative variations in the essential oil compositions of the
      different plant parts of L. wallichiana. (Z)-Falcarinol (1.9%-21.0%) and alpha
      funebrene (0.1%-10.1%) were reported for the first time from the essential oils
      of L. wallichiana.

PMID- 22978234
TI  - Determination of chemical constituents of leaf and stem essential oils of
      Artemisia monosperma from central Saudi Arabia.
AB  - The leaf and stem essential oils of Artemisia monosperma from the desert region
      of central Saudi Arabia were analysed by gas chromatography-based techniques (GC
      FID, GC-MS, Co-GC, LRI determination, database and literature search) using polar
      as well as non-polar columns, which resulted in the identification of 130
      components, of which 81 were common to both oils. In the leaf oil 120 compounds
      were identified, while 91 were identified in the stem oil accounting for 98.4%
      and 99.7% of the oil composition, respectively. The major constituents of the
      leaf oil were beta-pinene (50.3%), a-terpinolene (10.0%), limonene (5.4%) and a
      pinene (4.6%), while the major constituents of the stem oil were beta-pinene
      (36.7%), a-terpinolene (6.4%), limonene (4.8%), beta-maaliene (3.7%), shyobunone
      (3.2%) and a-pinene (3.1%). The two oils showed an important qualitative
      similarity. However, some specific constituents (39 in the leaf oil and 10 in the
      stem oil) allow differentiation of the two essential oils.

PMID- 22978235
TI  - Chemical composition of the essential oils of Centaurea formanekii and C.
      orphanidea ssp. thessala, growing wild in Greece.
AB  - The volatile constituents of the aerial parts of Centaureaformanekii Halacsy and
      the aerial parts, capitula and roots of C. orphanidea Heldr. & Sart. ex Boiss.
      ssp. thessala (Hausskn.) Dostal from Greece were extracted by hydrodistillation
      and analyzed. The main components in C. formanekii were hexadecanoic acid
      (13.6%), delta-elemene (9.1%), and spathulenol (6.9%). The main components in C.
      orphanidea ssp. thessala were gamma-elemene (26.1%) and caryophyllene oxide
      (13.2%) in the aerial parts, hexadecanoic acid (33.5%) and heptacosane (6.3%) in
      the capitula, and hexadecanoic acid methyl ester (22.0%) and a-chamigrene (14.0%)
      in the roots. The chemotaxonomic significance with respect to other previously
      studied species of the same sections (Phalolepis and Achrolopus, respectively) is
      discussed.

PMID- 22978236
TI  - Phytochemical profiles of volatile constituents from Centaurea ragusina leaves
      and flowers and their antimicrobial effects.
AB  - The volatile oils obtained from the leaves and flowers of the Croatian endemic
      plant Centaurea ragusina L. were evaluated for antimicrobial activity. The
      chemical compositions, determined by GC and GC-MS, were complex, with
      sesquiterpenes the most abundant class of compound. Nonterpene hydrocarbons were
      also identified in high quantities, while acids and ketones were found in high
      quantities only in the leaf volatile oil. Aldehydes, alcohols, esters and other
      compounds were identified in lower quantities. Antimicrobial effects of the
      volatile samples were investigated by using the disc diffusion and microdilution
      assays. They were found to inhibit a wide range of bacteria and fungi, causing in
      vitro growth inhibition at a concentration of 250 microg/mL. The volatile oils
      displayed great antibacterial potential with MIC values ranging from 16 to 128
      microg/mL against the Gram-positive bacteria Bacillus cereus, Clostridium
      perfringens, Enterococcus faecalis and Staphylococcus aureus, and lesser activity
      against the Gram-negative bacteria Cronobacter sakazakii, Escherichia coli,
      Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as fungal strains (MIC
      = 32-128 microg/mL).

PMID- 22978237
TI  - Chemical composition and antimicrobial activity of essential oil of different
      parts of Seseli rigidum.
AB  - The chemical composition and antimicrobial activity of the essential oil of the
      Balkan endemic species Seseli rigidum Waldst. & Kit. (Apiaceae) was investigated.
      The monoterpene alpha-pinene was predominant in the volatile oil from aerial
      parts (57.4%) and fruit (23.3%). In the essential oil of the aerial parts
      limonene (6.7%), camphene (5.8%) and sabinene (5.5%) were also present in high
      amounts, and in the fruit oil, beta-phellandrene (17.4%) and sabinene (12.9%). On
      the contrary, the root essential oil was composed almost entirely of the
      polyacetylene falcarinol (88.8%). The antimicrobial activity of the root
      essential oil was significant against Staphylococcus aureus, S. epidermidis,
      Micrococcus luteus and Enterococcus faecalis (MICs 6.25-25.00 microg/mL).
      Volatile constituents from the root strongly inhibited the growth of methicillin
      resistant strains of S. aureus (MICs 6.25-50.00 microg/mL). Anti-staphylococcal
      activity can be attributed to the main volatile constituent ofS. rigidum root,
      falcarinol.

PMID- 22978238
TI  - Chemical composition, olfactory analysis and antibacterial activity of Thymus
      vulgaris chemotypes geraniol, 4-thujanol/terpinen-4-ol, thymol and linalool
      cultivated in southern France.
AB  - The essential oils of four chemotypes of Thymus vulgaris L. (Lamiaceae) were
      analyzed for their composition and antibacterial activity to assess their
      different properties. GC-MS and GC-FID analyses revealed that the essentials oils
      can be classified into the chemotypes thymol (41.0% thymol), geraniol (26.4%
      geraniol), linalool (72.5% linalool) and 4-thujanol/terpinen-4-ol (42.2% cis- and
      7.3% trans-sabinene hydrate, 6.5 % terpinen-4-ol). The olfactory examination
      confirmed the explicit differences between these chemotypes. Furthermore,
      antibacterial activity was investigated against several strains of two Gram
      positive (Brochothrix thermosphacta and Staphylococcus aureus) and four Gram
      negative food-borne bacteria (Escherichia coli, Salmonella abony, Pseudomonas
      aeruginosa and P. fragi). All essential oil samples were demonstrated to be
      highly effective against Gram-positive strains, whereas the impact on Gram
      negative microorganisms was significantly smaller, but still considerable. The
      results obtained indicate that, despite their different properties, the essential
      oils of selected T. vulgaris chemotypes are potent antimicrobials to be employed
      as useful additives in food products as well as for therapeutic applications.

PMID- 22978239
TI  - Chemical composition, antimicrobial, antioxidant and cytotoxic activity of
      essential oils of Plectranthus cylindraceus and Meriandra benghalensis from
      Yemen.
AB  - The chemical composition, antimicrobial, antioxidant and cytotoxic activities of
      the essential oils isolated from the leaves of Plectranthus cylindraceus Hoechst.
      ex. Benth. (EOPC) and Meriandra benghalensis (Roxb.) Benth. (EOMB) were
      investigated. Sixteen compounds were identified in P. cylindraceus oil
      representing 94.5% of the oil content with thymol (68.5%), terpinolene (5.3%),
      beta-selinene (4.7%), beta-caryophyllene (4.0%), delta-cadinol (2.1%), and
      arcurcumene (1.7%) as the major compounds. In M. benghalensis oil, 12 compounds
      were identified, which made up 82.0% of the total oil. The most abundant
      constituents were camphor (43.6%), 1,8-cineole (10.7%), alpha-eudesmol (5.8%),
      caryophyllene oxide (5.8%), camphene (5.3%) and bomeol (3.4%). The antimicrobial
      activities of both oils were evaluated against five microorganisms with the disc
      diffusion test, the broth micro-dilution method and a semiquantitative
      bioautographic test. The most sensitive microorganisms for P. cylindraceus oil
      were S. aureus, B. subtilis, and C. albicans with inhibition zones of 38, 42, and
      43 mm and MIC values of 0.39, 0.18, and, 0.18 microL/mL, respectively. M.
      benghalensis oil showed weak to moderate activity against the tested
      microorganisms. 2,2-Diphenyl-l-picrylhydrazyl (DPPH) assay was employed to study
      the potential antioxidant activities of both oils. The antioxidant activity of P.
      cylindraceus oil (IC50 34.5 microg/mL) appeared to be higher than that of M.
      benghalensis oil (IC50 935 microg/mL). At a concentration of 100 microg/mL, EOMB
      showed a stronger cytotoxic activity, with growth inhibition of 71% against HT29
      tumor cells, than EOPC (18%).

PMID- 22978240
TI  - Electrophysiological responses of the Naupactus bipes beetle to essential oils
      from Piperaceae species.
AB  - Electrophysiological responses based on electroantennographic detection (GC-EAD)
      and electroantennography (EAG) analysis of Naupactus bipes beetles (Germar, 1824)
      (Coleoptera: Curculionidae: Brachycerinae) were used to test volatile oils of
      Piper gaudichaudianum, P. regnellii and P. hispidum. In the EAG experiments,
      female and male beetles showed significant EAG response to the three volatile
      oils of Piper species, with the females' responses slightly higher than the
      males'. The experiments with GC-EAD revealed that some terpenoids (namely, alpha
      pinene, beta-pinene, myrcene, alpha-copaene and germacrene) present in the leaf
      essential oils of the Piper species are perceptible to female and male beetles.

PMID- 22978241
TI  - Inhibition of essential bacterial peptidyl-tRNA hydrolase activity by tropical
      plant extracts.
AB  - Peptidyl-tRNA Hydrolase (Pth) is a highly conserved, essential enzyme in
      bacteria. It removes the peptide portion from peptidyl-tRNA, returning free tRNAs
      to participate in translation. Build-up of peptidyl-tRNAs is toxic and defects in
      Pth function result in cell death. Herein we use in vitro activity of recombinant
      E. coli Pth to screen tropical plant extracts for inhibition. Multiple extracts
      were found to have inhibitory activity with some exhibiting different inhibitory
      effects depending on extraction conditions. IC50 values ranged from 0.02 to >
      53.8 microg of extract per 1 unit of Pth, holding promise for in vivo screening.
      The inhibitory components in these extracts may serve as lead compounds for
      development of novel antibacterials.

PMID- 22978242
TI  - Analytical profiling of bioactive constituents from herbal products, using
      metabolomics--a review.
AB  - Natural products have been the source of many active substances in drug
      discovery. There are several strategies/approaches in the field of biology, drug
      discovery, molecular and cell biology for identification of bioactive molecules.
      Metabolomics involves fewer complexities, is more precise and provides more
      relevant data compared with other techniques. This approach is based on the
      application of new technologies and provides real-world end points that
      complement and help in the interpretation of genomic and proteomic data in drug
      discovery. It has also been proven to be a valuable analytical tool for the
      identification of secondary metabolites from medicinal plants, particularly for
      evidence-based development of new phytotherapeutical agents and nutraceuticals.
      This review outlines the different analytical techniques used to detect and
      measure the multiplexed metabolites and biomarkers in the herbal field.

PMID- 22978243
TI  - Simple detection of surface antigens on living cells by applying distinct cell
      positioning with negative dielectrophoresis.
AB  - We report the fabrication of two different cell patterns based on negative
      dielectrophoresis (n-DEP) and apply it to simple and rapid distinction of cells
      with specific surface antigens from a cell population. The DEP device for cell
      manipulation comprised a microfluidic channel with an upper indium tin oxide
      (ITO) electrode and a lower ITO-interdigitated band array (ITO-IDA) electrode
      modified with an antibody. Cells immediately accumulated on the surface in the
      gap area between both bands of the ITO-IDA electrode by n-DEP upon AC voltage
      between the upper ITO and both lower bands. Switching of the applied band
      electrode voltage resulted in the removal of accumulated cells to form another
      pattern because of the formation of a different electric field pattern in the
      device. Modifying the ITO-IDA surface with the antibody inhibited the removal of
      the cells with a specific surface antigen for irreversible capture by
      immunoreactions during the first accumulation. In this study, we targeted the
      CD33 surface antigen expressed on human promyelocytic leukemia cells (HL-60). The
      time required for the assay was substantially short: 60 s for forcing and 60 s
      for separating the unbound cells. Furthermore, the present method does not
      require pretreatment such as target labeling or washing of unbound cells.
      Moreover, the use of the swing technique considerably improved cell binding to
      the antibody-modified surface for cells with a specific surface antigen. The
      distinct integration of cells with n-DEP in the high conductivity medium provided
      higher cell binding efficiency compared to that obtained in our previous study
      (Hatanaka, H.; Yasukawa, T.; Mizutani, F. Anal. Chem., 2011, 83, 7207-7212)
      without loss of rapidity and simplicity.

PMID- 22978244
TI  - Homeopathic treatment of migraine in children: results of a prospective,
      multicenter, observational study.
AB  - OBJECTIVES: The study objective was to evaluate the effectiveness of homeopathic
      medicines for the prevention and treatment of migraine in children. DESIGN: This
      was an observational, prospective, open, nonrandomized, noncomparative,
      multicenter study. SETTING/LOCATION: The study was conducted in 12 countries
      worldwide. SUBJECTS: Fifty-nine (59) physicians trained in the prescription of
      homeopathic medicines and 168 children, aged 5-15 years, with definite or
      probable migraine diagnosed using International Headache Society 2004 criteria
      were the subjects in this study. INTERVENTIONS: Physicians were given complete
      freedom in terms of treatment prescription; thus, prescriptions were
      individualized for each patient. OUTCOME MEASURES: The frequency, intensity, and
      duration of migraine attacks in the 3 months prior to inclusion were compared
      with those during the 3-month follow-up period. Pertinent data were collected
      using questionnaires completed by the doctor and the patient or his/her
      parent/guardian. The secondary outcome measure was the impact of homeopathic
      medicines on education, measured as absence from school. RESULTS: The frequency,
      severity, and duration of migraine attacks decreased significantly during the 3
      month follow-up period (all p<0.001). Preventive treatment during this time
      consisted of homeopathic medicines in 98% of cases (mean=2.6 medicines/patient).
      Children spent significantly less time off school during follow-up than before
      inclusion (2.0 versus 5.5 days, respectively; p<0.001). The most common
      preventive medicines used were Ignatia amara (25%; mainly 9C), Lycopodium
      clavatum (22%), Natrum muriaticum (21%), Gelsemium (20%), and Pulsatilla (12%;
      mainly 15C). Homeopathy alone was used for the treatment of migraine attacks in
      38% of cases. The most commonly used medicines were Belladonna (32%; mainly 9C),
      Ignatia amara (11%; mainly 15C), Iris versicolor (10%; mainly 9C), Kalium
      phosphoricum (10%; mainly 9C), and Gelsemium (9%; mainly 15C and 30C).
      CONCLUSIONS: The results of this study demonstrate the interest of homeopathic
      medicines for the prevention and treatment of migraine attacks in children. A
      significant decrease in the frequency, severity, and duration of migraine attacks
      was observed and, consequently, reduced absenteeism from school.

PMID- 22978245
TI  - The effects of regular yoga practice on pulmonary function in healthy
      individuals: a literature review.
AB  - OBJECTIVES: Yoga is a popular form of exercise in the Western world, and yoga's
      effects on pulmonary function have been investigated previously. The purpose of
      this article is to review this research systematically and determine if regular
      yoga training improves pulmonary function in apparently healthy individuals.
      METHODS: Using the Alternative Health Watch, the Physical Education Index,
      Medline,((r)) and the SPORTdiscus databases; and the keywords yoga, respiration,
      and pulmonary function, a comprehensive search was conducted that yielded 57
      studies. Of these studies selections were made to include only experimental
      studies written in English, published in peer-reviewed journals after 1980, and
      investigating the effects of regular yoga practice on pulmonary function in
      healthy individuals participating in the studies. RESULTS: Yoga improved
      pulmonary function, as measured by maximum inspiratory pressure, maximum
      expiratory pressure, maximum voluntary ventilation, forced vital capacity, forced
      expiratory volume in 1 second, and peak expiratory flow rate, in all (N=9), but
      1, study. CONCLUSIONS: Overall, pulmonary function appears to improve with a
      minimum of 10 weeks of regular yoga practice, and the magnitude of this
      improvement is related to fitness level and/or the length of time the subjects
      spend practicing pranayama (i.e., breathing exercises). In other words, greater
      improvements in pulmonary function are more likely to be seen in less-fit
      individuals and/or those that engage in longer periods of pranayama. Additional
      studies examining various yoga practices are warranted to gain a more
      comprehensive understanding of the effects of yoga techniques on pulmonary
      functions.

PMID- 22978246
TI  - Use of assistance and therapy dogs for children with autism spectrum disorders: a
      critical review of the current evidence.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are characterized by deficits in
      social reciprocity and communication, and by unusually restricted, repetitive
      behaviors. Intervention strategies based on the exploitation of the emotional
      aspects of human-dog relationships hold the potential to overcome the difficulty
      of subjects with ASD to relate and interact effectively with others, targeting
      core symptoms of this disorder. METHODS: This review summarizes the results of
      six published studies on the effects of brief interactions with dogs and the
      effects of introducing dogs in families with a child diagnosed with ASD, with an
      emphasis on social behaviors and language use. Furthermore, the possible
      mechanisms responsible for the beneficial effects observed are discussed.
      CONCLUSIONS: Although the studies described here are encouraging, further
      research with better designs and using larger samples is needed to strengthen
      translation of such interventions to the clinic. In addition, potential
      applications of analyzing child-dog interactions are highlighted to screen for
      early signs of the disorder.

PMID- 22978247
TI  - Iron pyrite nanocubes: size and shape considerations for photovoltaic
      application.
AB  - Multiple lines of recent research indicate that iron pyrite (FeS(2)) requires a
      {100}-terminated crystal morphology in order to maintain semiconducting
      properties. Additionally, the large absorption coefficient of pyrite allows for
      the near complete absorption of above band gap radiation in <50 nm layers.
      However, to our knowledge <50 nm pyrite nanocubes have yet to be isolated.
      Herein, we demonstrate the synthesis of ~37 nm phase pure pyrite nanocubes by
      manipulating the sulfur chemical potential and ligand environment of the system.
      Ultraviolet-visible (UV-vis) absorption spectroscopy gives a signal of resonant
      light scattering indicating strong electronic coupling between nanocubes, which
      may allow for nanocube films with superior electron mobility. The absorption
      spectroscopies of cubic and irregular nanocrystals are contrasted and compared
      with recent theoretical work in order to investigate the effect of shape on
      electronic properties. Specifically, nanocubes have been found to have absorption
      characteristics closer to theory as compared to irregular nanocrystals,
      especially for UV radiation: 250-350 nm. Pyrite nanocubes display an indirect
      band gap at ~1.1 eV in addition to two direct transitions at ~1.9 and ~3.0 eV,
      correlating well to theoretical values.

PMID- 22978248
TI  - Rapid increases and time-lagged declines in amphibian occupancy after wildfire.
AB  - Climate change is expected to increase the frequency and severity of drought and
      wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be
      particularly vulnerable to these modified disturbance regimes because large
      wildfires often occur during extended droughts and thus may compound
      environmental threats. However, understanding of the effects of wildfires on
      amphibians in forests with long fire-return intervals is limited. Numerous stand
      replacing wildfires have occurred since 1988 in Glacier National Park (Montana,
      U.S.A.), where we have conducted long-term monitoring of amphibians. We measured
      responses of 3 amphibian species to fires of different sizes, severity, and age
      in a small geographic area with uniform management. We used data from wetlands
      associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether
      burn extent and severity and interactions between wildfire and wetland isolation
      affected the distribution of breeding populations. We measured responses with
      models that accounted for imperfect detection to estimate occupancy during
      prefire (0-4 years) and different postfire recovery periods. For the long-toed
      salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana
      luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21
      years after wildfire, occupancy for both species decreased >= 25% in areas where
      >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the
      boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests
      burned. This increase in occupancy was followed by a gradual decline. Our results
      show that accounting for magnitude of change and time lags is critical to
      understanding population dynamics of amphibians after large disturbances. Our
      results also inform understanding of the potential threat of increases in
      wildfire frequency or severity to amphibians in the region.

PMID- 22978249
TI  - Formation of zinc-containing nanoparticles from Zn2+ ions in cell culture media:
      implications for the nanotoxicology of ZnO.
AB  - Zinc ions generate a range of poorly soluble Zn-containing nanoparticles when
      added to commonly used mammalian cell culture media. The formation of these
      nanoparticles confounds the use of soluble Zn salts as positive controls during
      cytotoxicity testing of other Zn-containing nanoparticles, such as ZnO. These
      nanoprecipitates can either be crystalline or amorphous and vary in composition
      depending upon the concentration of Zn(II) within the medium. The cytotoxicity
      and immune system response of these nanoparticles in situ are similar to those of
      30 nm ZnO nanoparticles. The low residual level of truly soluble Zn species
      (taken as species passing through a 2 kDa membrane) in cell culture media with
      serum is insufficient to elicit any appreciable cytotoxicity. These observations
      highlight the importance of employing appropriate controls when studying ZnO
      nanoparticle toxicity and suggest a re-evaluation of the conclusions drawn in
      some previous cytotoxicity studies.

PMID- 22978251
TI  - Gemcitabine versus Modified Gemcitabine: a review of several promising chemical
      modifications.
AB  - Gemcitabine, an anticancer agent which acts against a wide range of solid tumors,
      is known to be rapidly deaminated in blood to the inactive metabolite 2',2'
      difluorodeoxyuridine and to be rapidly excreted by the urine. Moreover, many
      cancers develop resistance against this drug, such as loss of transporters and
      kinases responsible for the first phosphorylation step. To increase its
      therapeutic levels, gemcitabine is administered at high doses (1000 mg/m(2))
      causing side effects (neutropenia, nausea, and so forth). To improve its
      metabolic stability and cytotoxic activity and to limit the phenomena of
      resistance many alternatives have emerged, such as the synthesis of prodrugs.
      Modifying an anticancer agent is not new; paclitaxel or ara-C has been subjected
      to such changes. This review summarizes the various chemical modifications that
      can be found in the 4-(N)- and 5'-positions of gemcitabine. They can provide (i)
      a protection against deamination, (ii) a better storage and (iii) a prolonged
      release in the cell, (iv) a possible use in the case of deoxycytidine kinase
      deficiency, and (v) transporter deficiency. These new gemcitabine-based sysems
      have the potential to improve the clinical outcome of a chemotherapy strategy.

PMID- 22978253
TI  - A case of pacemaker related superior venacaval syndrome after thoracic surgery.

PMID- 22978252
TI  - Pharmacokinetic comparison of inhaled fixed combination vs. the free combination
      of beclomethasone and formoterol pMDIs in asthmatic children.
AB  - AIM: The fixed combination of beclomethasone (BDP) and formoterol pressurized
      metered dose inhaler (pMDI) (Foster(r), Chiesi Farmaceutici) is being developed
      in the lower strength (BDP/formoterol: 50/6 MUg) to provide an appropriate dosage
      for children with asthma. The aim of this work was to investigate the systemic
      bioavailability of beclomethasone-17-monoproprionate (B17MP, the active
      metabolite of BDP) and formoterol after single inhalation of Foster(r) pMDI 50/6
      MUg vs. the free combination of BDP and formoterol pMDIs in asthmatic children.
      METHODS: Children aged 5-11 years old inhaled BDP 200 MUg and formoterol 24 MUg
      as fixed vs. free combination in an open label, randomized, two way crossover
      single dose study. Blood was collected pre-dose up to 8 h post-dose for
      pharmacokinetic evaluation (AUC(0,t), AUC(0,infinity), AUC(0,0.5 h, Cmax , tmax ,
      t1/2 ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose
      and cortisol excretion. Peak expiratory flow and adverse events were monitored.
      RESULTS: Twenty subjects were evaluable. The systemic exposure of B17MP and
      formoterol administered as fixed combination did not exceed the free combination:
      B17MP AUC(0,t) (pg ml(-1)  h) ratio test : reference (90% CI), 0.81 (0.697,
      0.948) and formoterol AUC(0,t) (pg ml(-1)  h) ratio test : reference 0.97 (0.85,
      1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority
      in favour of the test drug. One adverse event (vertigo) occurred but was not
      considered treatment-related. CONCLUSION: BDP and formoterol pharmacokinetic and
      pharmacodynamic effects are non-superior after administration of the two actives
      as fixed vs. the free combination in 5-11-year-old asthmatic children.

PMID- 22978254
TI  - Interventions for preventing and reducing the use of physical restraints in long
      term geriatric care - a Cochrane review.
AB  - AIMS AND OBJECTIVES: To evaluate the effectiveness of interventions to prevent
      and reduce the use of physical restraints in older people requiring long-term
      nursing care. BACKGROUND: Physical restraints are commonly used in geriatric long
      term care. However, they are associated with adverse outcomes. Therefore, freedom
      from physical restraints should be the aim of high-quality nursing care. DESIGN:
      Systematic review of randomised controlled trials. METHODS: This review followed
      the methods of the Cochrane Handbook of systematic reviews of interventions. The
      systematic search (September 2009) covered the Cochrane Dementia and Cognitive
      Improvement Group's Specialized Register, MEDLINE, EMBASE, CINAHL, PsycINFO and
      LILACS. RESULTS: Six cluster-randomised controlled trials met the inclusion
      criteria. All studies investigated educational approaches targeting nursing
      staff. In addition, two studies offered consultation, two guidance and one
      support and free access to technical aids. Five studies examined nursing home
      residents and one study residents in group dwelling units. No studies in
      community settings were included. Overall, the methodological quality of studies
      was low. Their results were inconsistent. One study with good methodological
      quality in the nursing home setting documented an increase in physical restraints
      use in both groups, while the other four studies with lower quality found reduced
      use of physical restraints in the intervention group. The single study in group
      dwelling units found no change in physical restraints use in the intervention
      group but a significant increase in the control group. CONCLUSIONS: There is
      insufficient evidence supporting the effectiveness of educational interventions
      targeting nursing staff for preventing or reducing the use of physical restraints
      in geriatric long-term care. Relevance to clinical practice.  Our findings
      indicate that educational programmes targeting nursing staff might not be
      effective in reducing the use of physical restraints in geriatric long-term care.
      It remains unclear which components should be included in educational programmes
      aiming to reduce physical restraints.

PMID- 22978255
TI  - Are exhalation valves on N95 filtering facepiece respirators beneficial at low
      moderate work rates: an overview.
AB  - Exhalation valves (EVs) are touted as useful in dissipating humidity, heat, and
      carbon dioxide from the dead space of N95 filtering facepiece respirators and
      decreasing exhalation resistance, thereby making the respirator more comfortable
      and less physiologically demanding. Despite decades of use, there is limited
      research on the psychophysiological impact of EVs on the wearer at the current,
      low-moderate work rates of many workers. The available literature indicates that
      past and current EVs on the market decrease exhalation resistance to a variable
      degree and may improve dead space heat dissipation and, consequently, the
      temperature of the skin covered by the respirator. EVs have little substantial
      effect on dead space humidity, respiratory rate, heart rate, core temperature,
      speech intelligibility, or dead space oxygen and carbon dioxide levels at the
      aforementioned work rates. The studies also indicate that EVs may impact comfort
      and tolerance when N95 filtering facepiece respirators are worn for extended
      periods or at high work rates. Because comfort and tolerance impact respirator
      use compliance and, by extension, protection, more research into the
      psychophysiological impact of EVs on wearers and the development of new EVs
      tailored for low-moderate work rates are warranted.

PMID- 22978256
TI  - Hormone replacement therapy prescription: a disconnect between personal and
      patient prescribing.

PMID- 22978257
TI  - Understanding weight gain at menopause.
AB  - OBJECTIVE: The aim of this review was to summarize the literature regarding the
      impact of the menopause transition on body weight and body composition. METHODS:
      We conducted a search of the literature using Medline (Ovid, 1946-present) and
      PubMed (1966-2012) for English-language studies that included the following
      search terms: 'menopause', 'midlife', 'hormone therapy' or 'estrogen' combined
      with 'obesity', 'body weight' or 'body composition'. RESULTS: Whereas weight gain
      per se cannot be attributed to the menopause transition, the change in the
      hormonal milieu at menopause is associated with an increase in total body fat and
      an increase in abdominal fat. Weight excess at midlife is not only associated
      with a heightened risk of cardiovascular and metabolic disease, but also impacts
      adversely on health-related quality of life and sexual function. Animal and human
      studies indicate that this tendency towards central abdominal fat accumulation is
      ameliorated by estrogen therapy. Studies mostly indicate a reduction in overall
      fat mass with estrogen and estrogen-progestin therapy, improved insulin
      sensitivity and a lower rate of development of type 2 diabetes. CONCLUSION: The
      hormonal changes across the perimenopause substantially contribute to increased
      abdominal obesity which leads to additional physical and psychological morbidity.
      There is strong evidence that estrogen therapy may partly prevent this menopause
      related change in body composition and the associated metabolic sequelae.
      However, further studies are required to identify the women most likely to gain
      metabolic benefit from menopausal hormone therapy in order to develop evidence
      based clinical recommendations.

PMID- 22978259
TI  - Quantification of citrullination by means of skewed isotope distribution pattern.
AB  - Citrullination is a post-translational modification of arginine, resulting in a
      loss of positive charge and a 1 Da mass increase. Research on citrullinated
      proteins is crucial in rheumatoid arthritis, an autoimmune disease characterized
      by the presence of antibodies against citrullinated proteins. However, little is
      known about the location or quantity of deiminated arginine residues in these
      proteins. Since citrullination gives rise to a mass gain of only 1 Da, the
      isotope pattern of the citrullinated and the noncitrullinated version of a
      peptide will overlap. However, the difference between the theoretical, or
      noncitrullinated, and the measured isotope pattern can be used to quantify the
      amount of citrullination. We developed a method to quantify citrullinated
      peptides by means of their skewed isotopic distribution pattern. The method was
      first optimized with synthetic peptides, after both direct infusion and RP-HPLC
      separation on an ESi-QqTOF mass spectrometer. Additionally, we analyzed synovial
      fluid samples from rheumatoid arthritis patients and were able to quantify
      citrullinated peptides originating from citrullinated fibrinogen, a well-known
      antigen.

PMID- 22978260
TI  - Identification and analysis of the first 2009 pandemic H1N1 influenza virus from
      U.S. feral swine.
AB  - The first case of pandemic H1N1 influenza (pH1N1) virus in feral swine in the
      United States was identified in Texas through the United States Department of
      Agriculture (USDA) Wildlife Services' surveillance program. Two samples were
      identified as pandemic influenza by reverse transcriptase quantitative PCR (RT
      qPCR). Full-genome Sanger sequencing of all eight influenza segments was
      performed. In addition, Illumina deep sequencing of the original diagnostic
      samples and their respective virus isolation cultures were performed to assess
      the feasibility of using an unbiased whole-genome linear target amplification
      method and multiple sample sequencing in a single Illumina GAIIx lane. Identical
      sequences were obtained using both techniques. Phylogenetic analysis indicated
      that all gene segments belonged to the pH1N1 (2009) lineage. In conclusion, we
      have identified the first pH1N1 isolate in feral swine in the United States and
      have demonstrated the use of an easy unbiased linear amplification method for
      deep sequencing of multiple samples. 

PMID- 22978261
TI  - The complete mitochondrial genome of the codling moth Cydia pomonella
      (Lepidoptera: Tortricidae).
AB  - The complete mitochondrial genome of the codling moth Cydia pomonella
      (Lepidoptera: Tortricidae) was determined. The genome is 15,253 bp long with 37
      typical animal mitochondrial genes and an A+T-rich region. All genes are arranged
      in their conserved positions compared with the pupative ancestral arrangement of
      insects except for trnM, which was translocated to the upstream of the transfer
      RNA cluster trnI-trnQ as in all previously reported lepidopteran mitochondiral
      genomes. Seven portein-coding genes use ATG start codon and five use ATT.
      However, the cox1 gene uses the CGA start codon as it is found in all previous
      reported mitochondrial genomes of Lepidoptera. Nine protein-coding genes stop
      with termination codon TAA. Four protein-coding genes use incomplete stop codons
      TA or T. The A+T region is located between rrnS and trnM with a length of 331 bp.

PMID- 22978262
TI  - Problematizing health coaching for chronic illness self-management.
AB  - To address the growing costs associated with chronic illness care, many
      countries, both developed and developing, identify increased patient self
      management or self-care as a focus of healthcare reform. Health coaching, an
      implementation strategy to support the shift to self-management, encourages
      patients to make lifestyle changes to improve the management of chronic illness.
      This practice differs from traditional models of health education because of the
      interactional dynamics between nurse and patient, and an orientation to care that
      ostensibly centres and empowers patients. The theoretical underpinnings of
      coaching reflect these differences, however in its application, the practices
      arranged around health coaching for chronic illness self-management reveal the
      social regulation and professional management of everyday life. This becomes
      especially problematic in contexts defined by economic constraint and government
      withdrawal from activities related to the 'care' of citizens. In this paper, we
      trace the development of health coaching as part of nursing practice and consider
      the implications of this practice as an emerging element of chronic illness self
      management. Our purpose is to highlight health coaching as an approach intended
      to support patients with chronic illness and at the same time, problematize the
      tensions contained in (and by) this practice. 

PMID- 22978263
TI  - Synergism between hydrogen peroxide and seventeen acids against five agri-food
      borne fungi and one yeast strain.
AB  - AIMS: The objective of this study was to evaluate fungicidal efficacy of hydrogen
      peroxide administered in combination with 17 mineral and organic acids authorized
      for use in the food industry. METHODS AND RESULTS: The assays were performed on a
      96-well microplate using a microdilution technique based on the checkerboard
      titration method. The six selected strains (one yeast and five fungi) were
      reference strains and strains representative of contaminating fungi found in the
      food industry. Each synergistic hydrogen peroxide/acid combination found after
      fifteen minutes contact time at 20  degrees C in distilled water was then tested
      in conditions simulating four different use conditions. Twelve combinations were
      synergistic in distilled water, eleven of these remained synergistic with one or
      more of the four mineral and organic interfering substances selected. Hydrogen
      peroxide/formic acid combination remained effective against four strains and was
      never antagonistic against the other two fungi. Combinations with propionic acid
      and acetic acid stayed synergistic against two strains. Those with oxalic acid
      and lactic acid kept their synergism only against Candida albicans. No synergism
      was detected against Penicillium cyclopium. CONCLUSIONS: Synergistic combinations
      of disinfectants were revealed, among them the promising hydrogen peroxide/formic
      acid combination. SIGNIFICANCE AND IMPACT OF THE STUDY: A rapid screening method
      developed in our laboratory for bacteria was adapted to fungi and used to reveal
      the synergistic potential of disinfectants and/or sanitizers combinations.

PMID- 22978264
TI  - Functional enhancement of neuronal cell behaviors and differentiation by elastin
      mimetic recombinant protein presenting Arg-Gly-Asp peptides.
AB  - BACKGROUND: Integrin-mediated interaction of neuronal cells with extracellular
      matrix (ECM) is important for the control of cell adhesion, morphology, motility,
      and differentiation in both in vitro and in vivo systems. Arg-Gly-Asp (RGD)
      sequence is one of the most potent integrin-binding ligand found in many native
      ECM proteins. An elastin-mimetic recombinant protein, TGPG[VGRGD(VGVPG)6]20WPC,
      referred to as [RGD-V6]20, contains multiple RGD motifs to bind cell-surface
      integrins. This study aimed to investigate how surface-adsorbed recombinant
      protein can be used to modulate the behaviors and differentiation of neuronal
      cells in vitro. For this purpose, biomimetic ECM surfaces were prepared by
      isothermal adsorption of [RGD-V6]20 onto the tissue culture polystyrene (TCPS),
      and the effects of protein-coated surfaces on neuronal cell adhesion, spreading,
      migration, and differentiation were quantitatively measured using N2a
      neuroblastoma cells. RESULTS: The [RGD-V6]20 was expressed in E. coli and
      purified by thermally-induced phase transition. N2a cell attachment to either
      [RGD-V6]20 or fibronectin followed hyperbolic binding kinetics saturating around
      2 MUM protein concentration. The apparent maximum cell binding to [RGD-V6]20 was
      approximately 96% of fibronectin, with half-maximal adhesion on [RGD-V6]20 and
      fibronectin occurring at a coating concentration of 2.4 * 10-7 and 1.4 * 10-7 M,
      respectively. The percentage of spreading cells was in the following order of
      proteins: fibronectin (84.3% +/- 6.9%) > [RGD-V6]20 (42.9% +/- 6.5%) > [V7]20
      (15.5% +/- 3.2%) > TCPS (less than 10%). The migration speed of N2a cells on [RGD
      V6]20 was similar to that of cells on fibronectin. The expression of neuronal
      marker proteins Tuj1, MAP2, and GFAP was approximately 1.5-fold up-regulated by
      [RGD-V6]20 relative to TCPS. Moreover, by the presence of both [RGD-V6]20 and RA,
      the expression levels of NSE, TuJ1, NF68, MAP2, and GFAP were significantly
      elevated. CONCLUSION: We have shown that an elastin-mimetic protein consisting of
      alternating tropoelastin structural domains and cell-binding RGD motifs is able
      to stimulate neuronal cell behaviors and differentiation. In particular, adhesion
      induced neural differentiation is highly desirable for neural development and
      nerve repair. In this context, our data emphasize that the combination of
      biomimetically engineered recombinant protein and isothermal adsorption approach
      allows for the facile preparation of bioactive matrix or coating for neural
      tissue regeneration.

PMID- 22978265
TI  - Comparing frailty measures in their ability to predict adverse outcome among
      older residents of assisted living.
AB  - BACKGROUND: Few studies have directly compared the competing approaches to
      identifying frailty in more vulnerable older populations. We examined the ability
      of two versions of a frailty index (43 vs. 83 items), the Cardiovascular Health
      Study (CHS) frailty criteria, and the CHESS scale to accurately predict the
      occurrence of three outcomes among Assisted Living (AL) residents followed over
      one year. METHODS: The three frailty measures and the CHESS scale were derived
      from assessment items completed among 1,066 AL residents (aged 65+) participating
      in the Alberta Continuing Care Epidemiological Studies (ACCES). Adjusted risks of
      one-year mortality, hospitalization and long-term care placement were estimated
      for those categorized as frail or pre-frail compared with non-frail (or at
      high/intermediate vs. low risk on CHESS). The area under the ROC curve (AUC) was
      calculated for select models to assess the predictive accuracy of the different
      frailty measures and CHESS scale in relation to the three outcomes examined.
      RESULTS: Frail subjects defined by the three approaches and those at high risk
      for decline on CHESS showed a statistically significant increased risk for death
      and long-term care placement compared with those categorized as either not frail
      or at low risk for decline. The risk estimates for hospitalization associated
      with the frailty measures and CHESS were generally weaker with one of the frailty
      indices (43 items) showing no significant association. For death and long-term
      care placement, the addition of frailty (however derived) or CHESS significantly
      improved on the AUC obtained with a model including only age, sex and co
      morbidity, though the magnitude of improvement was sometimes small. The different
      frailty/risk models did not differ significantly from each other in predicting
      mortality or hospitalization; however, one of the frailty indices (83 items)
      showed significantly better performance over the other measures in predicting
      long-term care placement. CONCLUSIONS: Using different approaches, varying
      degrees of frailty were detected within the AL population. The various approaches
      to defining frailty were generally more similar than dissimilar with regard to
      predictive accuracy with some exceptions. The clinical implications and
      opportunities of detecting frailty in more vulnerable older adults require
      further investigation.

PMID- 22978266
TI  - The relationship between HBV serum markers and the clinicopathological
      characteristics of hepatitis B virus-associated glomerulonephritis (HBV-GN) in
      the northeastern chinese population.
AB  - BACKGROUND: To investigate the effect of HBV markers on HBV-GN. METHODS: The
      immunohistochemistry was used to detect HBsAg and HBcAg in frozen sections of
      renal biopsy, the changes in HBV serum markers, renal functional parameters and
      clinical manifestations or symptoms were observed to analyze renal damage.
      RESULTS: Using renal biopsy data from 329 cases, this study found that the most
      common pathological subtype in HBV-GN was mesangioproliferative
      glomerulonephritis (MsPGN) (24.9%, P <0.05), and 29.4% of patients who show
      serological HBsAg, HBeAg and anti-HBc positive developed membranoproliferative
      glomerulonephritis (MPGN) (P <0.05). The immunohistochemistry was used to detect
      HBsAg and HBcAg in frozen sections.50% of HBsAg and HBcAg deposits was observed
      in the glomeruli of MPGN patients, while 36.6% of HBsAg and 43.9% of HBcAg
      deposited in the glomeruli of MsPGN patients. The deposits of HBsAg and HBcAg in
      glomeruli were directly correlated with IgA, IgG, IgM and C3 deposits. In
      addition, cases with a moderate to severe decrease as reflected by the glomerular
      filtration rate (GFR) were predominantly patients with MPGN (31.6%, P <0.05) or
      MsPGN (21.1%, P <0.05). Patients who were serological HBsAg, HBeAg and anti-HBc
      positive or HBsAg, anti-HBe and anti-HBc positive mainly exhibited urine and
      renal parameter changes. CONCLUSION: Examination of HBV markers in serum and
      renal biopsy will be useful for clinicians to predict the renal damage in early
      stage when it is reversible in HBV-GN.

PMID- 22978267
TI  - Possible biochemical effects following inhibition of ethanol-induced gastric
      mucosa damage by Gymnema sylvestre in male Wistar albino rats.
AB  - CONTEXT: Gymnema sylvestre (GS) R. Br. (Gymnema) (Asclepiadaceae) has been used
      from ancient times as a folk medicine for the treatment of diabetes, obesity,
      urinary disorder, and stomach stimulation. OBJECTIVE: The present study was
      designed to investigate the effects of G. sylvestre leaves ethanol extract on
      gastric mucosal injury in rats. MATERIALS AND METHODS: Gastric mucosal damage was
      induced by 80% ethanol in 36 h fasted rats. The effect of G. sylvestre on gastric
      secretions induced in Shay rats was estimated. In stomach, wall mucus, non
      protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), total proteins and
      nucleic acids levels were estimated. Histopathological changes were observed.
      RESULTS: G. sylvestre pretreatment at doses of 100, 200 and 400 mg/kg provided
      27, 49, and 63% protection against the ulcerogenic effect of ethanol,
      respectively. Pylorus ligation accumulated 10.24 mL gastric secretions with 66.56
      mEq of acidity in control rats. Pretreatment with G. sylvestre significantly
      inhibited the secretions volume and acidity in dose-dependent manner. Ethanol
      caused significant depletion in stomach-wall mucus (p < 0.001), total proteins (p
      < 0.01), nucleic acids (p < 0.001), and NP-SH (p < 0.001) levels. Pretreatment
      with G. sylvestre showed protection against these depleted levels in dose
      dependent manner. The MDA levels increased from 19.02 to 29.22 nmol/g by ethanol
      ingestion and decreased with G. sylvestre pretreatments in dose-dependent manner.
      CONCLUSION: The protective effect of G. sylvestre observed in the present study
      is attributed to its effect on mucus production, increase in nucleic acid and NP
      SH levels, which appears to be mediated through its free radical scavenging
      ability and/or possible cytoprotective properties.

PMID- 22978269
TI  - 7,3'-dimethoxy hesperetin inhibits inflammation by inducing synovial apoptosis in
      rats with adjuvant-induced arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced
      inflammation and excessive synovial hyperplasia within affected joint. We
      previously reported 7, 3'-dimethoxy hesperetin (DMHP) as a highly anti
      inflammatory active derivative of hesperidin showed apparent pro-apoptotic effect
      in vitro on fibroblast-like synoviocytes of rats with adjuvant arthritis (AA), an
      animal model of RA. Here, we investigated the therapeutic effects of DMHP on
      inflammation and synovial apoptosis in rats with AA in vivo. Paw swelling,
      arthritis index, TNF-alpha and IL-1beta serum levels were measured to evaluate
      the effect of DMHP on inflammation in AA rats. DNA ladder detection and TUNEL
      assay were used to investigate the pro-apoptotic effect of DMHP on synovial
      apoptosis in vivo. Bcl-2, Bax mRNA and protein expressions in synovium were
      determined by real-time Q-PCR and western blot, respectively. We found DMHP
      inhibited secondary hind paw swelling and arthritis index, and decreased TNF
      alpha and IL-1beta serum levels in AA rats. Typical DNA ladder formation was
      found in DNA extraction of synovium from DMHP treated groups. The number of
      apoptotic synovial cells was elevated with DMHP treatment in TUNEL assay. DMHP
      markedly decreased Bcl-2 expression whereas increased Bax expression in synovium
      of AA rats at both transcription and protein levels. Moreover, DMHP treatment on
      AA rats significantly decreased the protein ratio of Bcl-2/Bax in synovium. In
      conclusion, DMHP has an apparent therapeutic effect on inflammation in rats with
      AA. Mechanisms of this effect are partly related to induction of synovial
      apoptosis through modulation of Bcl-2 and Bax expression.

PMID- 22978268
TI  - Prolonging the female reproductive lifespan and improving egg quality with
      dietary omega-3 fatty acids.
AB  - Women approaching advanced maternal age have extremely poor outcomes with both
      natural and assisted fertility. Moreover, the incidence of chromosomal
      abnormalities and birth defects increases with age. As of yet, there is no
      effective and practical strategy for delaying ovarian aging or improving oocyte
      quality. We demonstrate that the lifelong consumption of a diet rich in omega-3
      fatty acids prolongs murine reproductive function into advanced maternal age,
      while a diet rich in omega-6 fatty acids is associated with very poor
      reproductive success at advanced maternal age. Furthermore, even short-term
      dietary treatment with a diet rich in omega-3 fatty acids initiated at the time
      of the normal age-related rapid decline in murine reproductive function is
      associated with improved oocyte quality, while short-term dietary treatment with
      omega-6 fatty acids results in very poor oocyte quality. Thus, omega-3 fatty
      acids may provide an effective and practical avenue for delaying ovarian aging
      and improving oocyte quality at advanced maternal age.

PMID- 22978270
TI  - On the time course of bottom-up and top-down processes in selective visual
      attention: an EEG study.
AB  - According to recent models on visual attention, both the salience of signals
      (bottom-up) and the intention to search for particular stimuli (top-down) are
      determinants for attentional selection. We investigated these mechanisms by
      varying the top-down set of participants that had to detect either luminance or
      orientation changes of two symmetrically located bars. Irrelevant changes
      impaired target detection when they were presented spatially separated to the
      relevant change. Initial attentional selection was represented in posterior N1
      asymmetries and was determined by both the relative salience of orientation
      changes and a subsequent intentional bias towards relevant stimuli. Only when
      salient orientation changes interfered with luminance target selection in the N1
      time window did an N2pc occur. Thus, the selection of relevant information
      proceeds in a network whose activation is induced by a dynamic interplay of
      bottom-up and top-down processes.

PMID- 22978272
TI  - Influence of a poverty simulation on nursing student attitudes toward poverty.
AB  - This study aimed to determine a poverty simulation's influence on nursing
      students' attitudes toward poverty. Five cohorts of baccalaureate nursing
      students participated in the study; two cohorts (experimental group, n = 103)
      participated in the simulation and three did not (control group, n = 75). The
      Attitudes Towards Poverty Short Form was administered before the simulation and 6
      weeks later; higher scores indicated more positive attitudes toward poverty.
      Experimental group pretest scores were higher. Higher pretest global scores were
      negatively correlated with religious affiliation (Spearman's rho = -0.294, p =
      0.000) and positively correlated with prior poverty exposure (Spearman's rho =
      0.284, p = 0.000) and liberal political views (Spearman's rho = 0.444, p =
      0.000). Controlling for pretest differences, posttest mean scores for the
      experimental group (78.73) were significantly higher (p = 0.007). The poverty
      simulation is an engaging learning experience providing an opportunity for
      students to gain sensitivity in working with this population.

PMID- 22978271
TI  - Risk assessment of PM(2.5) to child residents in Brazilian Amazon region with
      biofuel production.
AB  - BACKGROUND: Exposure to fine fractions of particulate matter (PM(2.5)) is
      associated with increased hospital admissions and mortality for respiratory and
      cardiovascular disease in children and the elderly. This study aims to estimate
      the toxicological risk of PM(2.5) from biomass burning in children and
      adolescents between the age of 6 and 14 in Tangara da Serra, a municipality of
      Subequatorial Brazilian Amazon. METHODS: Risk assessment methodology was applied
      to estimate the risk quotient in two scenarios of exposure according to local
      seasonality. The potential dose of PM(2.5) was estimated using the Monte Carlo
      simulation, stratifying the population by age, gender, asthma and Body Mass Index
      (BMI). RESULTS: Male asthmatic children under the age of 8 at normal body rate
      had the highest risk quotient among the subgroups. The general potential average
      dose of PM(2.5) was 1.95 MUg/kg.day (95% CI: 1.62 - 2.27) during the dry scenario
      and 0.32 MUg/kg.day (95% CI: 0.29 - 0.34) in the rainy scenario. During the dry
      season, children and adolescents showed a toxicological risk to PM(2.5) of 2.07
      MUg/kg.day (95% CI: 1.85 - 2 .30). CONCLUSIONS: Children and adolescents living
      in the Subequatorial Brazilian Amazon region were exposed to high levels of
      PM(2.5) resulting in toxicological risk for this multi-pollutant. The
      toxicological risk quotients of children in this region were comparable or higher
      to children living in metropolitan regions with PM(2.5) air pollution above the
      recommended limits to human health.

PMID- 22978273
TI  - A systematic integrated literature review of systematic integrated literature
      reviews in nursing.
AB  - As faculty members, we frequently find that first-year doctoral students in
      nursing are confused about how to conduct a systematic integrated literature
      review. This could be due to its vague definition and a lack of recent literature
      that provides directions for conducting a systematic integrated literature
      review. This article aims to provide directions for conducting a systematic
      integrated literature review by identifying the essential components of published
      literature reviews in nursing. To achieve this goal, the literature was searched
      by using the keywords nursing, systematic, and review in multiple databases. A
      total of 267 articles were selected and are included in this systematic
      integrated literature review. The articles were then sorted by study design and
      analyzed in six areas of interests. Finally, a practical guideline for conducting
      systematic integrated literature reviews is proposed based on the analysis of the
      literature.

PMID- 22978274
TI  - A literature review of mentoring for RN-to-FNP transition.
AB  - Making the transition from RN to family nurse practitioner (FNP) can be
      challenging and stressful. The transition may begin during graduate school. As
      FNP students struggle to balance the multitude of academic, personal, and
      professional demands, they may also struggle with how to make the transition in
      role and practice. Nurse faculty may aid FNP students by mentoring them. However,
      information is limited regarding successful mentoring programs and faculty
      mentoring of FNP students. A literature review of mentoring was conducted, and
      findings are presented and discussed in this article, including recommendations
      for additional research. This information may assist faculty, students, and
      academic institutions seeking to better facilitate the RN-to-FNP transition
      during graduate school.

PMID- 22978275
TI  - Use of personal phones by senior nursing students to access health care
      information during clinical education: staff nurses' and students' perceptions.
AB  - Research indicates that having electronic resources readily available increases
      learners' ability to make clinical decisions and confidence in patient care. This
      mixed-method, descriptive pilot study collected data about senior prelicensure
      nursing students using smartphones, a type of mobile electronic device (MED), in
      the clinical area. The smartphones contained nursing diagnosis, pharmacology, and
      laboratory information; an encyclopedia; and the MEDLINE database. Student (n =
      7) data about smartphone use during a 10-week clinical rotation were collected
      via student-recorded usage logs and focus group recordings. Staff nurses' (n = 5)
      perceptions of students' use of smartphones for clinical educational resources
      were collected by anonymous survey. Both the focus group transcript and staff
      surveys were evaluated and the themes summarized by content analysis. Positive
      results and barriers to use, such as cost and technological comfort levels, are
      discussed. The results may help nurse educators and administrators initiate
      further research of MEDs as a clinical resource.

PMID- 22978276
TI  - Intermediate levels of transmitted antiretroviral drug resistance in Midwestern
      Brazil.

PMID- 22978277
TI  - Antiadipogenic activity of isohamnetin 3-O-beta-D-glucopyranoside from Salicornia
      herbacea.
AB  - In the present study, effect of flavonoid glucopyranoside, isorhamnetin 3-O-beta
      D-glucopyranoside, from Salicornia herbacea on adipogenic differentiation were
      evaluated in 3T3-L1 adipocytes. Confluent 3T3-L1 preadipocytes in medium (0.5 mM
      methylisobutylxanthine, 0.25 uM dexamethasone, 5 ug/mL insulin, and 10% fetal
      bovine serum [FBS]) were differentiated into adipocytes for 6 days with/without
      isorhamnetin 3-O-beta-D-glucopyranoside. The presence of isorhamnetin 3-O-beta-D
      glucopyranoside effectively suppressed adipogenic differentiation by
      downregulation of peroxisome proliferator-activated receptor-gamma (PPARgamma),
      CCAAT/enhancer-binding proteins (C/EBPalpha), sterol regulatory element-binding
      protein 1 (SREBP1), and the adipocyte-specific proteins. Moreover, the specific
      mechanism mediating the effects of isorhamnetin 3-O-beta-D-glucopyranoside was
      confirmed by activation of AMP-activated protein kinase (AMPK). These findings
      suggest that isorhamnetin 3-O-beta-D-glucopyranoside exerts antiadipogenic
      activity through AMPK activation. This study should find the nutraceutical value
      of S. herbacea-derived glucopyranoside, isorhamnetin 3-O-beta-D-glucopyranoside,
      as potent candidate of antiobesity agent via alleviation of lipid accumulation.

PMID- 22978278
TI  - The effect of a multicomponent literacy instruction model on literacy growth for
      kindergartners and first-grade students in Chile.
AB  - In the present study we examined the impact of a comprehensive literacy
      instruction model called Collaborative Language and Literacy Instruction Project
      (CLLIP) on language and literacy achievement over the course of a year by Spanish
      speaking children in Chile. Participants included kindergartners (N = 312) from
      high and low socioeconomic backgrounds and first-grade students (N = 305) from
      high SES families. The CLLIP model targeted phonological awareness, alphabetics
      and phonics, fluency, vocabulary, reading comprehension and writing, and included
      coaching and sustained follow-up as key elements for teacher professional
      development. The results showed promise for the CLLIP model in the Chilean
      context. Kindergartners in CLLIP classrooms had faster growth rates in letter
      naming, word reading, vocabulary, and phonemic segmentation fluency than those in
      control classrooms, and had higher scores at the end of the year in phonemic
      segmentation fluency, letter naming, and word reading. In addition,
      kindergartners from high SES families had faster growth rates than kindergartners
      from low SES families in letter naming and word reading. Effect sizes ranged from
      small (d = .18 in word reading) to fairly large (d = .70 in letter-naming
      fluency). First-grade students in CLLIP classrooms had faster growth rates than
      students in control classrooms in vocabulary, nonword reading fluency, word
      reading, and reading comprehension. Effect sizes were small in vocabulary,
      nonword reading fluency, and reading comprehension (.23 <= d <= .28) and medium
      in word reading (d = .50). These results suggest that the present multicomponent
      literacy instructional model had a positive impact on Chilean children's literacy
      acquisition.

PMID- 22978280
TI  - Introduction: lesbians, sexuality, and Islam.

PMID- 22978281
TI  - Naming to empower: lesbianism in the Arab Islamicate world today.
AB  - After a brief review of the proliferation of newly coined Arabic words to speak
      about LGBTQIA (lesbian, gay, bisexual, transgender, queer, intersex, and ally)
      identities, this article interrogates the facile imitation of Western labels and
      questions their usefulness in the context of Arab societies and cultures. It
      demonstrates that the assumptions that underlie the creation of new wordlists
      overlook and ultimately erase the very rich tradition on alternative sexual
      practices that has been prominent in the Islamicate world at least since the
      ninth century. Salvaging this tradition and its accompanying terminology on
      homosexuality challenges the claim that homosexuality is a Western importation,
      and renders the recourse to English categories superfluous. Moreover, uncovering
      the forgotten Arabic cultural material on alternative sexualities offers
      contemporary Arab gays and lesbians a rich and empowering indigenous heritage, as
      well as home-grown modes of resistance that are poised to challenge homophobic
      attitudes and policies in the Arab world, and the hegemony of Western sexual and
      cultural imperialism.

PMID- 22978282
TI  - My Qarina, my self: The homoerotic as Islamic feminism in Alifa Rifaat's "My
      World of the Unknown".
AB  - In Alifa Rifaat's "My World of the Unknown," the female narrator's homoerotic
      encounter with a djinn functions as a radical brand of Islamic feminism that
      challenges Arabo-Islamic cultural perceptions of female sexuality as threatening.
      Rifaat reinterprets Islamic teachings and Arabic folklore to show how women's
      sexuality must be revered rather than feared.

PMID- 22978284
TI  - Islam, sexuality, and the marginal positioning of Pengkids and their girlfriends
      in malaysia.
AB  - Drawing on the lived experiences of the Pengkids and their girlfriends in the
      deprived district of the capital city of Malaysia, Kuala Lumpur, this article
      examines transgender practices and women's same-sex desires within the local
      contexts of urbanization and political Islam. This article questions the assumed
      marginal positions of transgender practices and same-sex desires in society, and
      provides a nuanced understanding of the politics of identity, gender, sexuality
      and religion involved in a Muslim country. While the Muslim-Malay sexual
      minorities are increasingly subjected to the threats of moral policing in
      Malaysia, Pengkid has become a new identity marker for the marginalized sexual
      subject framed by the Islamic discourse of this country.

PMID- 22978283
TI  - The "invention" of lesbian acts in Iran: interpretative moves, hidden
      assumptions, and emerging categories of sexuality.
AB  - This article describes and explains the current official status of lesbianism in
      Iran. Our central question is why the installation of an Islamic government in
      Iran resulted in extreme regulations of sexuality. The authors argue that rather
      than a clear adoption of "Islamic teaching on lesbianism," the current regime of
      sexuality was "invented" through a series of interpretative moves, adoption of
      hidden assumptions, and creation of sexual categories. This article is organized
      into two sections. The first sets the scene of official sexuality in Iran through
      a summary of (1) the sections of the Iranian Penal code dealing with same-sex
      acts and (2) government support for sexual reassignment surgeries. The second
      section traces the "invention" of a dominant post-revolutionary Iranian view of
      Islam and sexuality through identifying a number of specific interpretive moves
      this view builds on.

PMID- 22978285
TI  - "I don't want to taint the name of Islam": the influence of religion on the lives
      of Muslim lesbians.
AB  - Islam is characterized as an extremely homophobic religion, which strictly
      forbids the union of two people of the same sex. This belief causes an
      immeasurable amount of strain and anxiety for lesbians because their feelings,
      desires, and emotions are considered "unnatural" and aberrant. The homophobic
      Islamic model of homosexuality thus celebrates heteronormative performances of
      gender and sexuality. In the present study, the issue of how religious identity
      interplays with sexual identity is examined. Using data gained from online
      interviews with five Muslim lesbians, the article considers whether the women are
      able to create their lesbian identity within a discourse that negates their
      sexual orientation. Their lives as Muslim lesbians produces a unique intersection
      where religion and sexuality converge, yet they are forced apart by religiously
      sanctioned homophobia, preventing them from exploring and expressing their
      sexuality. The article further examines whether Islam is a source upon which the
      women draw strength to understand their sexuality and to cope with being in the
      closet. Despite being members of Imaan, a Muslim LGBT (lesbian, gay, bisexual,
      and transgender) support group, the women continue to experience a significant
      degree of conflict. A reconciliation of faith with their sexuality is undermined
      by an unrelenting and intolerant religious attitude toward homosexuality.

PMID- 22978286
TI  - Siraat-e-Mustaqeem or the straight path.
AB  - This article focuses on conversations the author had with a middle-class, urban,
      working Muslim lesbian and her partner in Karachi, Pakistan. The couple discuss
      their lives within the framework of Islamic culture of South Asia. The author
      attempts to explore how women-loving- women define and construct knowledge about
      their sexuality, about non-normative forms of sexual relations/preferences, and
      how they negotiate the imagined and real restrictions placed on their sexuality
      by religion, society, and family, and the impact of such control mechanisms on
      women's health and emotional well-being, mobility, education, livelihood, sexual
      behaviors, and expression of desire.

PMID- 22978288
TI  - Validating metabolic syndrome through principal component analysis in a medically
      diverse, realistic cohort.
AB  - BACKGROUND: The concept of metabolic syndrome has been subject to etiological and
      clinical controversies in recent years. Associations among the five risk factors
      (obesity, hypertension, hyperglycemia, high triglyceride levels, and low high
      density lipoprotein cholesterol) may help establish the validity of the concept,
      especially in a cohort representative of an actual population. METHODS: We used
      principal component analysis (PCA) to analyze the structure of the physiological
      components of metabolic syndrome in 7213 patients contained in an administrative
      database for the Centre Hospitalier Universitaire de Sherbrooke in Sherbrooke,
      Quebec, a realistic cohort with diverse medical histories. We validated the
      results by repeating the analysis on stratified and random subgroups of patients,
      and on different combinations of risk factors. The first axis of the PCA was used
      to predict coronary heart disease (CHD) and diabetes. RESULTS: The two first axes
      explained 53% of the variance. The first axis (33%) was associated in the
      expected direction with all five predictor variables, consistent with its
      interpretation as metabolic syndrome. The first axis was more predictive of
      subsequent CHD and diabetes than the formal definition of metabolic syndrome.
      CONCLUSIONS: These results suggest that the concept of metabolic syndrome
      accurately captures an existing underlying physiological process. A continuous
      indicator could be constructed to identify metabolic syndrome more accurately,
      thus improving risk assessment for CHD and diabetes mellitus. Metabolic syndrome
      can be measured well even without all five predictors. However, discrepancies
      with other studies suggest that our results may not be generalizable, perhaps
      because our cohort tends to be sicker.

PMID- 22978289
TI  - Probing solvation in ionic liquids via the electrochemistry of the DPPH radical.
AB  - The electrochemistry of the radical species 2,2-diphenyl-1-picrylhydrazyl, DPPH,
      has been studied in a range of common ionic liquids and its voltammetric response
      found to vary with the choice of anion. The trend observed is used to provide a
      relative Lewis basicity scale of nine ionic liquids commonly used as solvents.

PMID- 22978290
TI  - Inhalable microparticles containing nitric oxide donors: saying NO to
      intracellular Mycobacterium tuberculosis.
AB  - Although nitric oxide (NO) is a bactericidal component of the macrophage's innate
      response to intracellular infections such as tuberculosis (TB), prolonged
      inhalation of NO gas has little benefit in chemotherapy of TB. The impact of
      controlled release of NO through intracellular delivery of NO donors to
      macrophages infected in vitro with Mycobacterium tuberculosis (Mtb) was
      investigated. Inhalable microparticles (MP) were prepared by spray-drying.
      Isosorbide mononitrate (ISMN), sodium nitroprusside (SNP), and diethylenetriamine
      nitric oxide adduct (DETA/NO) were incorporated in poly(lactic-co-glycolic acid)
      (PLGA) with encapsulation efficiencies of >90% to obtain MP yields of ~70%. The
      mass median aerodynamic diameter (MMAD) of the MP was 2.2-2.4 MUm within
      geometric standard deviations (GSD) of <=0.1 MUm. MP were phagocytosed by THP-1
      derived macrophages in culture and significantly (P < 0.05) sustained NO
      secretion into culture supernatant from 6 to 72 h in comparison to equivalent
      amounts of drugs in solution. Significantly (P < 0.05) higher dose-dependent
      killing of intracellular Mtb by MP compared to equivalent amounts of drugs in
      solution was observed on estimation of colony forming units (CFU) surviving 24 h
      after exposure to drugs or MP. The cytotoxicity of MP toward macrophages was
      lower than that of dissolved drugs. It was concluded that inhalable MP can target
      NO donors to the macrophage, control NO release in the macrophage cytosol, and
      reduce Mtb CFU by up to 3-log in 24 h, at doses that are much lower than those
      required for cardiovascular effects.

PMID- 22978291
TI  - Calcium binding and ionic conduction in single conical nanopores with polyacid
      chains: model and experiments.
AB  - Calcium binding to fixed charge groups confined over nanoscale regions is
      relevant to ion equilibrium and transport in the ionic channels of the cell
      membranes and artificial nanopores. We present an experimental and theoretical
      description of the dissociation equilibrium and transport in a single conical
      nanopore functionalized with pH-sensitive carboxylic acid groups and phosphonic
      acid chains. Different phenomena are simultaneously present in this basic problem
      of physical and biophysical chemistry: (i) the divalent nature of the phosphonic
      acid groups fixed to the pore walls and the influence of the pH and calcium on
      the reversible dissociation equilibrium of these groups; (ii) the asymmetry of
      the fixed charge density; and (iii) the effects of the applied potential
      difference and calcium concentration on the observed ionic currents. The
      significant difference between the carboxylate and phosphonate groups with
      respect to the calcium binding is clearly observed in the corresponding current
      voltage (I-V) curves and can be rationalized by using a simple molecular model
      based on the grand partition function formalism of statistical thermodynamics.
      The I-V curves of the asymmetric nanopore can be described by the Poisson and
      Nernst-Planck equations. The results should be of interest for the basic
      understanding of divalent ion binding and transport in biological ion channels,
      desalination membranes, and controlled drug release devices.

PMID- 22978293
TI  - Thickness determination of subnanometer layers using laser ablation inductively
      coupled plasma mass spectrometry.
AB  - Laser ablation inductively coupled plasma mass spectrometry has been applied to
      determine the thickness of subnanometer (subnm) metallic layers. Metallic Nd was
      deposited onto Si wafers with 0.5, 1, 3, and 6 nm thickness and covered by a 10
      nm Al coating. Integrated ion signals corresponded to the layer thickness,
      indicating that external calibration provides accurate data. Utilizing
      sensitivity ratios obtained from ablation of a glass standard reference material
      (SRM) and the Al layer as reference, the deviations between prepared and measured
      layer thickness were less than 10%. A further attempt was made to determine the
      layer thickness with the absolute sensitivity obtained from ablation of a glass
      SRM. The approach also yielded a linear correlation between determined and actual
      layer thickness, but bias and interday variability were significantly higher.
      This is assumed to result from imprecise determination of the crater size when
      ablating the glass SRM. This study shows that subnm layers of metals can be
      analyzed for their thickness either using reference materials of identical
      composition or using sensitivity ratios when one layer can be used as a
      reference. Absolute determination of the layer thickness is less accurate but can
      circumvent the lack of reference materials of similar composition.

PMID- 22978292
TI  - A physiologically based in silico model for trans-2-hexenal detoxification and
      DNA adduct formation in rat.
AB  - trans-2-Hexenal (2-hexenal) is an alpha,beta-unsaturated aldehyde that occurs
      naturally in a wide range of fruits, vegetables, and spices. 2-Hexenal as well as
      other alpha,beta-unsaturated aldehydes that are natural food constituents or
      flavoring agents may raise a concern for genotoxicity due to the ability of the
      alpha,beta-unsaturated aldehyde moiety to react with DNA. Controversy remains,
      however, on whether alpha,beta-unsaturated aldehydes result in significant DNA
      adduct formation in vivo at realistic dietary exposure. In this study, a rat
      physiologically based in silico model was developed for 2-hexenal as a model
      compound to examine the time- and dose-dependent detoxification and DNA adduct
      formation of this selected alpha,beta-unsaturated aldehyde. The model was
      developed based on in vitro and literature-derived parameters, and its adequacy
      was evaluated by comparing predicted DNA adduct formation in the liver of rats
      exposed to 2-hexenal with reported in vivo data. The model revealed that at an
      exposure level of 0.04 mg/kg body weight, a value reflecting estimated daily
      human dietary intake, 2-hexenal is rapidly detoxified predominantly by
      conjugation with glutathione (GSH) by glutathione S-transferases. At higher dose
      levels, depletion of GSH results in a shift to 2-hexenal oxidation and reduction
      as the major pathways for detoxification. The level of DNA adduct formation at
      current levels of human dietary intake was predicted to be more than 3 orders of
      magnitude lower than endogenous DNA adduct levels. These results support that
      rapid detoxification of 2-hexenal reduces the risk arising from 2-hexenal
      exposure and that at current dietary exposure levels, DNA adduct formation is
      negligible.

PMID- 22978294
TI  - Some challenges to progressive control of foot and mouth disease in Pakistan-
      findings of a pilot survey.
AB  - Pakistan is at an initial stage for progressive control of foot and mouth disease
      (FMD). Understanding the risk factors for introduction, spread and persistence of
      the infection is important to design an evidence-based disease control programme.
      A rapid appraisal method was adopted, and a convenient sample of twenty
      commercial dairy farmers was interviewed. The following were considered to
      contribute in secondary transmission of infection: (i) intermediaries and service
      providers [animal health workers, animal traders and transporters, raw milk
      collectors, persons who remove skin of dead animals], (ii) places where animals
      come in close contact [livestock markets, animal fairs, communal grazing
      pastures, routes in villages where livestock move, watering points, animal
      transport vehicles], (iii) use of bulls immediately after recovery from FMD
      infection, (iv) range land/desert livestock production, (v) small holder sheep
      and goat production, (vi) purchase of replacement stock and fodder from infected
      locations. This article reveals contacts within and between villages, some of
      which may act as routes of transmission of FMD. The study suggests the need for
      zoosanitary education of the livestock keepers. 

PMID- 22978295
TI  - Proteomics wants cRacker: automated standardized data analysis of LC-MS derived
      proteomic data.
AB  - The large-scale analysis of thousands of proteins under various experimental
      conditions or in mutant lines has gained more and more importance in hypothesis
      driven scientific research and systems biology in the past years. Quantitative
      analysis by large scale proteomics using modern mass spectrometry usually results
      in long lists of peptide ion intensities. The main interest for most researchers,
      however, is to draw conclusions on the protein level. Postprocessing and
      combining peptide intensities of a proteomic data set requires expert knowledge,
      and the often repetitive and standardized manual calculations can be time
      consuming. The analysis of complex samples can result in very large data sets
      (lists with several 1000s to 100,000 entries of different peptides) that cannot
      easily be analyzed using standard spreadsheet programs. To improve speed and
      consistency of the data analysis of LC-MS derived proteomic data, we developed
      cRacker. cRacker is an R-based program for automated downstream proteomic data
      analysis including data normalization strategies for metabolic labeling and label
      free quantitation. In addition, cRacker includes basic statistical analysis, such
      as clustering of data, or ANOVA and t tests for comparison between treatments.
      Results are presented in editable graphic formats and in list files.

PMID- 22978296
TI  - Transepithelial phototherapeutic keratectomy for recurrent corneal erosions in a
      patient with previous corneal collagen cross-linking.
AB  - PURPOSE: To report the significant visual and topographic improvement of a
      patient who had corneal collagen cross-linking (CXL) performed and was
      subsequently treated with transepithelial phototherapeutic keratectomy (t-PTK)
      for recurrent corneal erosions. METHODS: A 36-year-old woman presented with
      recurrent corneal erosions in the right eye due to foreign body corneal trauma 1
      month prior to presentation. The patient had undergone CXL treatment for
      keratoconus on the same eye 1 year prior to presentation. After failed
      conservative treatment consisting of epithelial debridement and lubrication with
      artificial tears, the patient underwent t-PTK. RESULTS: Four months after t-PTK,
      corneal erosions did not recur and the patient remained asymptomatic. Slit-lamp
      examination revealed a clear cornea. The patient showed significant visual and
      topographic improvement after t-PTK. CONCLUSIONS: Transepithelial PTK for
      recurrent corneal erosions in a postoperative CXL patient successfully treated
      the corneal pathology, and visual and topographic improvement were observed.

PMID- 22978297
TI  - Residual astigmatism following toric intraocular lens implantation related to
      pupil size.
AB  - PURPOSE: To present two patients with residual astigmatism following toric
      intraocular lens (IOL) implantation. METHODS: Case reports. RESULTS: A 58-year
      old woman underwent toric IOL implantation (spherical power 29.50 diopters [D],
      cylinder power 3.00 D; SN60T5, Alcon Laboratories Inc) to correct 2.33 D @ 80
      degrees  of corneal astigmatism. Postoperatively, uncorrected distance visual
      acuity (UDVA) was 20/30 and corrected distance visual acuity (CDVA) was 20/22 (0 
      1.75 * 95), indicating an overcorrection of astigmatism. Slit-lamp examination
      demonstrated no IOL misalignment. Wavefront aberrometry showed a large pupil
      diameter (>6 mm) and a lower corneal astigmatism in a 6-mm zone (-1.40 D @ 174
      degrees ) compared to a 4-mm zone (-2.21 D @ 171 degrees ). The second patient, a
      60-year-old man, underwent multifocal toric IOL implantation (spherical power
      22.50 D, cylinder power 2.25 D; SND1T4, Alcon Laboratories Inc) to correct 1.51 D
      @ 173 degrees  of corneal astigmatism. Postoperatively, UDVA was 20/50 and CDVA
      was 20/20 (+0.25 -1.00 * 102), indicating an undercorrection of astigmatism. Slit
      lamp examination showed no misalignment. CONCLUSIONS: Both cases indicate that
      unexplained residual astigmatism following toric IOL implantation may be the
      result of multiple factors: the effect of the spherical power and anterior
      chamber depth on toric IOL calculations, the effect of posterior corneal
      astigmatism, and the effect of a large pupil size. The first two issues may be
      compensated for by improving toric IOL calculations. The latter indicates that
      pupillometry is indicated in relatively young patients who undergo toric IOL
      implantation.

PMID- 22978299
TI  - Looking into myself: changes in interoceptive sensitivity during mirror self
      observation.
AB  - Interoceptive sensitivity is an essential component of recent models of "the
      self." Increased focus on the self (e.g., self-observation in a mirror) can
      enhance aspects of self-processing. We examined whether self-observation also
      enhances interoceptive sensitivity. Participants performed a heartbeat detection
      task while looking at their own face in a mirror or at a black screen. There was
      significant improvement in interoceptive sensitivity in the mirror condition for
      those participants with lower interoceptive sensitivity at baseline. This effect
      was independent of the order of conditions, gender, age, body mass index,
      habitual exercise, and changes in heart rate. Our results suggest that self
      observation may represent a viable way of manipulating individuals' interoceptive
      sensitivity, in order to directly test causal relations between interoceptive
      sensitivity and exteroceptive self-processing.

PMID- 22978300
TI  - Interpretation of water level changes in the high plains aquifer in Western
      Kansas.
AB  - Water level changes in wells provide a direct measure of the impact of
      groundwater development at a scale of relevance for management activities.
      Important information about aquifer dynamics and an aquifer's future is thus
      often embedded in hydrographs from continuously monitored wells. Interpretation
      of those hydrographs using methods developed for pumping-test analyses can
      provide insights that are difficult to obtain via other means. These insights are
      demonstrated at two sites in the High Plains aquifer in western Kansas. One site
      has thin unconfined and confined intervals separated by a thick aquitard. Pumping
      induced responses in the unconfined interval indicate a closed (surrounded by
      units of relatively low permeability) system that is vulnerable to rapid
      depletion with continued development. Responses in the confined interval indicate
      that withdrawals are largely supported by leakage. Given the potential for rapid
      depletion of the unconfined interval, the probable source of that leakage, it is
      likely that large-scale irrigation withdrawals will not be sustainable in the
      confined interval beyond a decade. A second site has a relatively thick
      unconfined aquifer with responses that again indicate a closed system. However,
      unlike the first site, previously unrecognized vertical inflow can be discerned
      in data from the recovery periods. In years of relatively low withdrawals, this
      inflow can produce year-on-year increases in water levels, an unexpected
      occurrence in western Kansas. The prevalence of bounded-aquifer responses at both
      sites has important ramifications for modeling studies; transmissivity values
      from pumping tests, for example, must be used cautiously in regional models of
      such systems.

PMID- 22978301
TI  - Autobiographical memory in multiple sclerosis patients: assessment and cognitive
      facilitation.
AB  - The multifocal nature of lesions in multiple sclerosis hints at the occurrence of
      autobiographical memory (AbM) impairment. However, the dearth of studies on AbM
      in multiple sclerosis is noticeable, notwithstanding the importance of AbM in
      everyday life. In the first section of this study, 25 multiple sclerosis patients
      and 35 controls underwent a detailed episodic AbM assessment. Results obtained by
      means of ANOVA suggested an AbM retrieval deficit in every patient. That pattern
      of performance paved the way for the second section of the study, in which we
      followed up 10 out of the 25 patients. Our objective was to assess the
      effectiveness of a cognitive facilitation programme designed to alleviate AbM
      retrieval deficits, based on the key role of mental visual imagery on AbM.
      Statistical group analyses by means of ANOVA and individual analyses using the
      chi(2) test showed significant differences in AbM test results, in post
      facilitation relative to pre-facilitation training, in all 10 patients. Moreover,
      the patients' comments showed that the positive effects were transferred in their
      daily life functioning. We would like to suggest that the facilitation programme
      efficiently enhanced the process of self-centred mental visual imagery, which
      might have compensated for poor retrieval of personal memories by providing
      better access to visual details and detailed visual scenes of personal
      recollections.

PMID- 22978302
TI  - Citation classics: Top 50 cited articles in 'respiratory system'.
AB  - Identifying citation classics in the field is one of the key methodologies used
      to conduct a systematic evaluation of research performance. The objective of this
      study was to determine the most frequently cited articles published in journals
      that are placed under the 'respiratory system' subject category (Institute for
      Scientific Information (ISI) Journal Citation Reports) and to compare them with
      the most frequently cited respiratory-related articles published in any journal,
      regardless of subject category. The authors utilized the ISI Journal Citation
      Reports: Science Edition 2010 database in April 2012 to determine the most
      frequently cited articles by respiratory system subject category and by
      respiratory-related keywords. The top 50 most-cited articles were identified in
      each category and evaluated according to various characteristics. The majority of
      these papers originated from the United States. The median numbers of citations
      for the top 50 cited articles stratified by respiratory system subject category
      and respiratory-related keywords were 841.5 and 2701, respectively. Half of the
      top 50 cited articles identified by respiratory-related keywords were published
      in general medical or basic science journals, whereas only three out of these
      were published in journals under the respiratory system subject category in ISI
      Journal Citation Reports. In summary, respiratory-related articles published in
      general medical or science journals attracted more citations than those published
      in the specific respiratory journals.

PMID- 22978303
TI  - Evaluation of cardiac phenotype in horses with type 1 polysaccharide storage
      myopathy.
AB  - BACKGROUND: Type 1 polysaccharide storage myopathy (PSSM1), an equine glycogen
      storage disorder caused by a gain of function mutation (R309H) in the gene
      encoding glycogen synthase (GYS1), is associated with the accumulation of amylase
      resistant alpha-crystalline polysaccharide inclusions within skeletal muscle.
      Several glycogenoses in humans have a cardiac phenotype, and reports exist of
      horses with PSSM and polysaccharide inclusions in cardiac muscle.
      HYPOTHESIS/OBJECTIVES: To investigate the hypothesis that horses with PSSM1
      display a cardiac phenotype. Our objectives were to compare plasma cardiac
      troponin I (cTnI) concentration and the incidence of cardiac arrhythmias in PSSM1
      homozygotes, heterozygotes, and control horses. METHODS: One hundred and twenty
      five Belgian and Percheron horses under the same management were genotyped for
      the R309H GYS1 mutation. From these, 8 age-, breed-, and sex-matched cohorts of
      each genotype were identified. Plasma cTnI concentration and incidence of cardiac
      arrhythmias (determined by 24-hour Holter ECG) were compared between the groups.
      RESULTS: Although some PSSM1-affected horses had mildly increased plasma cTnI
      concentrations, there was no significant difference in cTnI concentrations
      between groups. There were no significant differences in the incidence of ectopic
      beats, cardiac conduction intervals or mean heart rate between groups.
      CONCLUSIONS AND CLINICAL IMPORTANCE: We found no evidence of clinically relevant
      cardiac myocyte injury or arrhythmias in horses with PSSM1. Additional study is
      required to determine whether myocardial function may be compromised in this
      disorder.

PMID- 22978304
TI  - Anti-infectivity of camel polyclonal antibodies against hepatitis C virus in
      Huh7.5 hepatoma.
AB  - PURPOSE: To extend the study of the camel milk proteins which have antiviral
      activity against HCV, camel naive polyclonal IgGs, alpha-lactalbumin were
      purified from camel milk and their anti-HCV effect was examined using PBMCs and
      Huh7.5 cell-lines. They were compared with the activity of human polyclonal IgGs
      and camel lactoferrin and casein. MATERIAL AND METHODS: Three types of
      experiments were performed on PBMCs and HuH7.5 cell. HCV was directly incubated
      with the purified proteins and then mixed with both cell types, or the proteins
      were incubated with the cells and then exposed to HCV, or the HCV pre-infected
      cells were treated with the proteins to inhibit intracellular replication. The
      proteins were added to cells or virus at different concentrations and time
      intervals. RESULTS: Pretreated PBMCs and Huh7.5 cells with milk proteins were not
      protected when exposed to HCV infection. The direct interaction between HCV and
      camel IgGs and camel lactoferrin (cLf) led to a complete inhibition of HCV entry
      into cells, while casein, alpha-lactalbumin and human IgGs failed to inhibit HCV
      entry at any tested concentration. Camel IgGs showed ability to recognize HCV
      peptides with a significant titer (12 * 10(3)) in comparison with human IgGs
      which failed to do it. Camel lactoferrin was capable of inhibiting the
      intracellular HCV replication at concentrations of 0.25-1.25 mg/ml. CONCLUSION:
      Camel milk naive polyclonal IgGs isolated from camel milk could inhibit the HCV
      infectivity and demonstrated strong signal against its synthetic peptides.
      Lactoferrin inhibit the HCV infectivity started from 0.25 mg/ml. However, alpha
      lactalbumin, human IgGs and casein failed to demonstrate any activity against HCV
      infectivity.

PMID- 22978305
TI  - Mastoiditis and Gradenigo's Syndrome with anaerobic bacteria.
AB  - BACKGROUND: Gradenigo's syndrome is a rare disease, which is characterized by
      the triad of the following conditions: suppurative otitis media, pain in the
      distribution of the first and the second division of trigeminal nerve, and
      abducens nerve palsy. The full triad may often not be present, but can develop if
      the condition is not treated correctly. CASE PRESENTATION: We report a case of a
      3-year-old girl, who presented with fever and left-sided acute otitis media. She
      developed acute mastoiditis, which was initially treated by intravenous
      antibiotics, ventilation tube insertion and cortical mastoidectomy. After 6 days
      the clinical picture was complicated by development of left-sided abducens palsy.
      MRI-scanning showed osteomyelitis within the petro-mastoid complex, and a hyper
      intense signal of the adjacent meninges. Microbiological investigations showed
      Staphylococcus aureus and Fusobacterium necrophorum. She was treated successfully
      with intravenous broad-spectrum antibiotic therapy with anaerobic coverage. After
      8 weeks of follow-up there was no sign of recurrent infection or abducens palsy.
      CONCLUSION: Gradenigo's syndrome is a rare, but life-threatening complication to
      middle ear infection. It is most commonly caused by aerobic microorganisms, but
      anaerobic microorganisms may also be found why anaerobic coverage should be
      considered when determining the antibiotic treatment.

PMID- 22978307
TI  - Associations between pollen counts, pollutants, and asthma-related hospital
      admissions in a high-density Indian metropolis.
AB  - BACKGROUND: The seasonal pattern of asthma-related hospitalization has often been
      correlated with ambient allergen/pollutant levels. OBJECTIVE: To examine the
      relationship between asthma-related hospital admissions (ARHA) and outdoor
      pollen, spore, and pollutant levels for adult patients in a densely populated
      Indian megacity Kolkata. METHODS: ARHA data were obtained from two major teaching
      hospitals of the city. Pollen and spores causing allergic sensitization were
      identified by skin prick tests (SPTs) among respiratory allergic subjects (N =
      1353). Outdoor concentrations of aeroallergens were determined using a Burkard
      sampler for five consecutive years (2004-2009). Levels of NO(2), SO(2), suspended
      particulate matters (SPMs), and respirable particulate matters (RPMs) were made
      available by West Bengal Pollution Control Board (WBPCB, Government of West
      Bengal). Poisson multivariate Poisson regression (with adjustments for
      overdispersion) was used to model the data. Results. We found that ARHA in
      Kolkata increased with predictable regularity in March and September, while
      remaining low in January and July. SPT showed highly positive skin reactions with
      grass/weed and palm pollens in respiratory allergic patients, while Aspergilli
      spores also evoked good sensitivity. In our regression model, the airborne pollen
      types, Cheno-Amaranthaceae and Cyperaceae, and the inorganic pollutant, SO(2) and
      RPM, were significantly associated with ARHA (p < .05). CONCLUSION: ARHA in the
      megacity of Kolkata shows two seasonal peaks that can be correlated with outdoor
      grass/weed pollen and RPM concentrations. In contrast, the city's ambient fungal
      spore counts were not found to be significantly associated.

PMID- 22978308
TI  - Mannitol challenge does not confirm bronchial hyperreactivity in some histamine
      responsive asthmatic children.
AB  - OBJECTIVE: The aim of this study was to compare the usefulness of mannitol
      provocation test to that of classical histamine challenge in children with
      PC(20)FEV(1) histamine lower than 4 mg/ml. METHODS: Twenty-two adolescent
      patients (mean age of 15.4 +/- 4.1 years) with established asthma (PC(20)FEV(1)
      histamine below 4 mg/ml) were included in this study. Bronchial challenge with
      mannitol was performed 1-2 days after the test with histamine. RESULTS: The
      fraction of positive results of mannitol test was markedly lower when compared
      with the histamine challenge (72.7% vs. 100%, p = .015). The test was
      discontinued in one case due to severe coughing after inhalation of 315 mg of
      mannitol. Coughing during inhalation of dry mannitol powder occurred in most
      patients, although drinking water after subsequent doses alleviated this symptom
      in nearly all of them. Of note, triboelectrification of the inhaler and capsules
      was observed during the administration of consecutive mannitol doses, markedly
      hindering the delivery of this provoking agent. The relative decrease in FEV(1)
      resulting from bronchial provocation was significantly lower following mannitol
      delivery when compared with the histamine test (70.3% vs. 81.6% of resting value,
      p < .001). Significant correlation was not observed between the values of
      PC(20)FEV(1) histamine and PD(15)FEV(1) mannitol levels. CONCLUSIONS: Bronchial
      challenge with mannitol can be used as a screening test in everyday practice, but
      one cannot exclude bronchial hyperresponsiveness based on its negative results.
      Moreover, its usefulness is limited by the influence of static on the delivery of
      sequential mannitol doses and coughing which can be often associated with
      mannitol inhalation.

PMID- 22978309
TI  - Patients with asthma benefit from concomitant therapy with cineole: a placebo
      controlled, double-blind trial.
AB  - BACKGROUND AND AIMS: Cineole is the main constituent of eucalyptus oil, and it is
      mainly used as a mucolytic agent in inflammatory airway diseases. With its known
      mucolytic, bronchodilating, and anti-inflammatory effects, cineole reduces the
      exacerbation rate in patients suffering from chronic obstructive pulmonary
      disease. Based on these pharmacodynamic effects, we arrived at the hypothesis
      that asthma patients would benefit from concomitant therapy with cineole.
      METHODS: As part of a double-blind, placebo-controlled, multicenter study, 247
      patients with confirmed asthma were randomly selected according to the guidelines
      for this study. All patients were administered 200 mg of cineole, or a placebo,
      three times per day as a concomitant therapy over a period of 6 months. The
      combined primary outcome measures, which were implemented as a multiple criteria
      testing process, were improvement of lung function, asthma symptoms, and quality
      of life. RESULTS: Following the completion of the 6-month treatment period, it
      was noted that the patient group treated with cineole showed significantly more
      improvements to the multiple testing criteria than the patients in the placebo
      group (p = .0027). The statistical significance of the individual outcome
      measures could also be proven in accordance with the Wei-Lachin procedure (i.e.,
      for Forced expiratory Volume 1 Second, p = .0398; for asthma symptoms, p = .0325;
      and for Asthma Quality of Life Questionnaire (AQLQ), p = .0475). CONCLUSION:
      Concomitant therapy using cineole can lead to notable improvement in lung
      function and health condition as well as to reduce dyspnea in asthma patients.

PMID- 22978310
TI  - Corticosteroid timing and length of stay for children with asthma in the
      Emergency Department.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between time of
      corticosteroid administration to children with asthma exacerbations in the
      Emergency Department (ED) and length of stay (LOS). We hypothesized
      administration within 60 minutes would be associated with a 10- minute or greater
      decrease in mean LOS. METHODS: A retrospective chart review of 882 patients was
      conducted. Children between the ages of 2 and 18 years presented to the
      Connecticut Children's Medical Center's (CCMC's) ED with an acute asthma
      exacerbation were included. Children were excluded if they did not receive oral
      corticosteroids in the ED, had significant co-morbidities, were currently taking
      corticosteroids, or had taken them within the past 7 days. Children receiving
      corticosteroids within 60 minutes of triage were compared with children receiving
      corticosteroids for 61 minutes or later. The primary outcome was mean LOS.
      RESULTS: Children treated with corticosteroids within 60 and 61 minutes or later
      had similar age, gender, insurance, and disposition. Children treated with
      corticosteroids within 60 minutes had a 25-minute decrease in LOS compared with
      children treated for 61-minute or later (95% CI: 15-35), p < .0001. CONCLUSIONS:
      Administering corticosteroids to pediatric asthma patients in the ED within an
      hour of triage is associated with a 25-minute mean decrease in LOS. With large
      numbers of asthma visits, a 25-minute decrease in LOS for each child could have a
      significant impact on patient throughput in the ED.

PMID- 22978312
TI  - Evaluation of four pretreatment procedures for MALDI-TOF MS yeast identification
      in the routine clinical laboratory.
AB  - MALDI-TOF MS-based yeast identification requires a pretreatment step for which
      four are described in the literature, i.e., direct smear, fast formic acid and
      two complete formic acid/acetonitrile extractions. In this study we compared the
      impact of these procedures on the performance of MALDI-TOF MS-based yeast
      identification of samples from colonies grown on Sabouraud or chromogenic media.
      A total of 103 yeast isolates recovered from clinical samples were identified in
      parallel using the four pretreatment procedures. The proportions of both correct
      identifications (regardless of LogScore values) and of reliable identifications
      (i.e., correct identifications with a LogScore ?2, as recommended by the
      manufacturer) obtained with the four techniques were compared. Even if the
      proportion of correct identifications exceeded 85% independent of the
      pretreatment procedure, results obtained with complete formic acid/acetonitril
      extractions of colonies grown on Sabouraud media were significantly superior to
      those with smear and fast formic acid extraction procedures. If one considers
      only reliable identifications, then both smear and fast formic acid extraction
      procedures yielded lower (<40%) correct identification rates than the use of the
      two complete extraction procedures (>77%) of portions of colonies on both
      Sabouraud and chromogenic media. The data would indicate that the direct smear
      and fast formic acid procedures cannot be recommended due to the LogScore values
      which were continually below those recommended by the manufacturer for biological
      validation. Thus, complete extraction methods are better suited for MALDI-TOF MS
      based yeast identification in the clinical laboratory setting although they are
      more labor-intensive.

PMID- 22978315
TI  - Disentangling evolutionary signals: conservation, specificity determining
      positions and coevolution. Implication for catalytic residue prediction.
AB  - BACKGROUND: A large panel of methods exists that aim to identify residues with
      critical impact on protein function based on evolutionary signals, sequence and
      structure information. However, it is not clear to what extent these different
      methods overlap, and if any of the methods have higher predictive potential
      compared to others when it comes to, in particular, the identification of
      catalytic residues (CR) in proteins. Using a large set of enzymatic protein
      families and measures based on different evolutionary signals, we sought to break
      up the different components of the information content within a multiple sequence
      alignment to investigate their predictive potential and degree of overlap.
      RESULTS: Our results demonstrate that the different methods included in the
      benchmark in general can be divided into three groups with a limited mutual
      overlap. One group containing real-value Evolutionary Trace (rvET) methods and
      conservation, another containing mutual information (MI) methods, and the last
      containing methods designed explicitly for the identification of specificity
      determining positions (SDPs): integer-value Evolutionary Trace (ivET), SDPfox,
      and XDET. In terms of prediction of CR, we find using a proximity score
      integrating structural information (as the sum of the scores of residues located
      within a given distance of the residue in question) that only the methods from
      the first two groups displayed a reliable performance. Next, we investigated to
      what degree proximity scores for conservation, rvET and cumulative MI (cMI)
      provide complementary information capable of improving the performance for CR
      identification. We found that integrating conservation with proximity scores for
      rvET and cMI achieved the highest performance. The proximity conservation score
      contained no complementary information when integrated with proximity rvET.
      Moreover, the signal from rvET provided only a limited gain in predictive
      performance when integrated with mutual information and conservation proximity
      scores. Combined, these observations demonstrate that the rvET and cMI scores add
      complementary information to the prediction system. CONCLUSIONS: This work
      contributes to the understanding of the different signals of evolution and also
      shows that it is possible to improve the detection of catalytic residues by
      integrating structural and higher order sequence evolutionary information with
      sequence conservation.

PMID- 22978316
TI  - Electric field-induced emission enhancement and modulation in individual CdSe
      nanowires.
AB  - CdSe nanowires show reversible emission intensity enhancements when subjected to
      electric field strengths ranging from 5 to 22 MV/m. Under alternating positive
      and negative biases, emission intensity modulation depths of 14 +/- 7% are
      observed. Individual wires are studied by placing them in parallel plate
      capacitor-like structures and monitoring their emission intensities via single
      nanostructure microscopy. Observed emission sensitivities are rationalized by the
      field-induced modulation of carrier detrapping rates from NW defect sites
      responsible for nonradiative relaxation processes. The exclusion of these states
      from subsequent photophysics leads to observed photoluminescence quantum yield
      enhancements. We quantitatively explain the phenomenon by developing a kinetic
      model to account for field-induced variations of carrier detrapping rates. The
      observed phenomenon allows direct visualization of trap state behavior in
      individual CdSe nanowires and represents a first step toward developing new
      optical techniques that can probe defects in low-dimensional materials.

PMID- 22978320
TI  - Role of imbalance of eicosanoid pathways and staphylococcal superantigens in
      chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a multifactorial disease of the upper airways
      with a high prevalence (approximately 11%) in the general population. Different
      immune and inflammatory mechanisms are involved in its pathogenesis. Alterations
      in the arachidonic acid pathway (leading to an imbalanced production of
      eicosanoids) have been linked to the pathophysiology of different diseases
      especially nasal polyposis, asthma, and aspirin-exacerbated respiratory disease.
      Furthermore, viral and bacterial infections have been identified as important
      factors amplifying the pro-inflammatory reactions in these pathologies. This
      review summarizes the impact of an imbalance in the eicosanoid pathway and the
      effect of Staphylococcus aureus enterotoxins on the regulation of the pro
      inflammatory network in CRS and their translation into disease severity.

PMID- 22978318
TI  - Half-life prolongation of therapeutic proteins by conjugation to ATIII-binding
      pentasaccharides: a first-in-human study of CarboCarrier(r) insulin.
AB  - AIM: Conjugation to antithrombin III ATIII-binding pentasaccharides has been
      proposed as a novel method to extend the half-life of therapeutic proteins. We
      aim to validate this technological concept in man by performing a first-in-human
      study using CarboCarrier(r) insulin (SCH 900948) as an example. A rising single
      dose phase 1 study was performed assessing safety, tolerability, pharmacokinetics
      and relative bioactivity of CarboCarrier(r) insulin. Safety, tolerability and
      pharmacokinetics (PK) of single doses of CarboCarrier(r) insulin in healthy
      volunteers were explored, and the dose-response relationship and relative
      bioactivity of CarboCarrier(r) insulin in subjects with type 2 diabetes were
      investigated. METHODS: After an overnight fast, subjects were randomized to a
      treatment sequence. PK and pharmacodynamic (glucose, insulin and C-peptide)
      samples were obtained for up to 72 h post-dose. Effects of CarboCarrier(r)
      insulin were compared with those of NPH-insulin. RESULTS: CarboCarrier(r) insulin
      was safe and well-tolerated and no consistent pattern of adverse events occurred.
      CarboCarrier(r) insulin exposure (Cmax and AUC) increased proportionally with
      dose. The mean terminal elimination half-life ranged between 3.11 and 5.28 h. All
      CarboCarrier(r) insulin dose groups showed decreases in the mean change from
      baseline of plasma glucose concentrations compared with the placebo group.
      CONCLUSIONS: CarboCarrier(r) insulin is pharmacologically active showing features
      of insulin action in man. The elimination half-life of the molecule was clearly
      extended compared with endogenous insulin, indicating that conjugation to ATIII
      binding pentasaccharides is a viable approach to extend the half-life of
      therapeutic proteins in humans. This is an important step towards validation of
      the CarboCarrier(r) technology by making use of CarboCarrier(r) insulin as an
      example.

PMID- 22978322
TI  - Stress-associated H3K4 methylation accumulates during postnatal development and
      aging of rhesus macaque brain.
AB  - Epigenetic modifications are critical determinants of cellular and developmental
      states. Epigenetic changes, such as decreased H3K27me3 histone methylation on
      insulin/IGF1 genes, have been previously shown to modulate lifespan through gene
      expression regulation. However, global epigenetic changes during aging and their
      biological functions, if any, remain elusive. Here, we examined the histone
      modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual
      rhesus macaques at different ages by chromatin immunoprecipitation, followed by
      deep sequencing (ChIP-seq) at the whole genome level. Through integrative
      analysis of the ChIP-seq profiles with gene expression data, we found that
      H3K4me2 increased at promoters and enhancers globally during postnatal
      development and aging, and those that correspond to gene expression changes in
      cis are enriched for stress responses, such as the DNA damage response. This
      suggests that metabolic and environmental stresses experienced by an organism are
      associated with the progressive opening of chromatin. In support of this, we also
      observed increased expression of two H3K4 methyltransferases, SETD7 and DPY30, in
      aged macaque brain.

PMID- 22978323
TI  - High yield of culture-based diagnosis in a TB-endemic setting.
AB  - BACKGROUND: In most of the world, microbiologic diagnosis of tuberculosis (TB) is
      limited to microscopy. Recent guidelines recommend culture-based diagnosis where
      feasible. METHODS: In order to evaluate the relative and absolute incremental
      diagnostic yield of culture-based diagnosis in a high-incidence community in Cape
      Town, South Africa, subjects evaluated for suspected TB had their samples
      processed for microscopy and culture over a 21 month period. RESULTS: For 2537
      suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one
      positive smear and 29.9% (760) had at least one positive culture. One culture
      yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0%
      (absolute yield). Based on the latter value, the number of cultures needed to
      diagnose (NND) one extra case of TB was 8, compared to 19 if second specimens
      were submitted for microscopy. CONCLUSION: In a high-burden setting, the
      introduction of culture can markedly increase TB diagnosis over microscopy. The
      concept of number needed to diagnose can help in comparing incremental yield of
      diagnosis methods. Although new promising diagnostic molecular methods are being
      implemented, TB culture is still the gold standard.

PMID- 22978324
TI  - Phosphorylation on threonine 11 of beta-dystrobrevin alters its interaction with
      kinesin heavy chain.
AB  - Dystrobrevin family members (alpha and beta) are cytoplasmic components of the
      dystrophin-associated glycoprotein complex, a multimeric protein complex first
      isolated from skeletal muscle, which links the extracellular matrix to the actin
      cytoskeleton. Dystrobrevin shares high homology with the cysteine-rich and C
      terminal domains of dystrophin and a common domain organization. The beta
      dystrobrevin isoform is restricted to nonmuscle tissues, serves as a scaffold for
      signaling complexes, and may participate in intracellular transport through its
      interaction with kinesin heavy chain. We have previously characterized the
      molecular determinants affecting the beta-dystrobrevin-kinesin heavy chain
      interaction, among which is cAMP-dependent protein kinase [protein kinase A
      (PKA)] phosphorylation of beta-dystrobrevin. In this study, we have identified
      beta-dystrobrevin residues phosphorylated in vitro by PKA with pull-down assays,
      surface plasmon resonance measurements, and MS analysis. Among the identified
      phosphorylated residues, we demonstrated, by site-directed mutagenesis, that
      Thr11 is the regulatory site for the beta-dystrobrevin-kinesin interaction. As
      dystrobrevin may function as a signaling scaffold for kinases/phosphatases, we
      also investigated whether beta-dystrobrevin is phosphorylated in vitro by kinases
      other than PKA. Thr11 was phosphorylated by protein kinase C, suggesting that
      this represents a key residue modified by the activation of different signaling
      pathways.

PMID- 22978325
TI  - The effect of music-movement therapy on physical and psychological states of
      stroke patients.
AB  - AIMS AND OBJECTIVES: This study evaluated the effects of combined music-movement
      therapy on physical and psychological functioning of hospitalised stroke
      patients. BACKGROUND: Few studies have focused on music-movement therapy's
      effects on physical and psychological functioning of stroke patients. DESIGN: A
      quasi-experimental design with pre- and post-tests was used. METHODS: A
      convenience sample was used: patients hospitalised for stroke and within two
      weeks of the onset of stroke were randomised to either an experimental group
      (received music-movement therapy in their wheelchairs for 60 minutes three times
      per week for 8 weeks) or control group (received only routine treatment). The
      effect of music-movement therapy was assessed in terms of physical outcomes
      (range of motion, muscle strength and activities of daily living) and
      psychological outcomes (mood states, depression), measured in both groups pre-
      and post-test. RESULTS: The experimental group had significantly increased
      shoulder flexion and elbow joint flexion in physical function and improved mood
      state in psychological function, compared with the control group. CONCLUSIONS:
      Early rehabilitation of hospitalised stroke patients within two weeks of the
      onset of stroke was effective by using music-movement therapy. It improved their
      mood state and increased shoulder flexion and elbow joint flexion. RELEVANCE TO
      CLINICAL PRACTICE: The findings of this study suggest that rehabilitation for
      stroke patients should begin as early as possible, even during their
      hospitalisation. Nursing practice should incorporate the concept of combining
      music and movements to improve stroke patients' physical and psychological states
      starting from the acute phase.

PMID- 22978326
TI  - Anti-obesity effect of kimchi fermented with Weissella koreensis OK1-6 as starter
      in high-fat diet-induced obese C57BL/6J mice.
AB  - AIMS: In this study, we investigated the anti-obesity effects of kimchi (Korean
      traditional fermented vegetable) fermented either without starter culture or with
      a specific starter culture, Weissella koreensis OK1-6. METHODS AND RESULTS:
      C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high-fat
      diet), HF-KC (high-fat diet containing 3% kimchi manufactured without starter)
      and HF-KCO (high-fat diet containing 3% kimchi manufactured with the starter
      culture W. koreensis OK1-6). After 12 weeks of dietary intervention, the mice
      were killed, and serum and tissue samples were examined. Serum and hepatic lipid
      profile, insulin, leptin concentration and expression level of lipid anabolic
      genes like peroxisome proliferator-activated receptor gamma, stearoyl-CoA
      desaturase-1, liver X receptor alpha and SREBP2 were significantly decreased
      (<0.05) along with body and epididymal fat pad weight in the HF-KCO group
      compared with the HF-KC and HF group. CONCLUSIONS: These results suggested that
      kimchi fermented with the starter W. koreensis OK1-6 has anti-obesity effects in
      HF-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may
      contribute to nutraceutical and food industries in developing functional food and
      probiotics based therapies for the treatment and prevention of obesity.

PMID- 22978327
TI  - Therapeutic monoclonal antibodies: strategies and challenges for biosimilars
      development.
AB  - Biosimilar medicines already on the market may have a primary structure identical
      to their reference products (e.g., amino acid sequences should be identical). In
      the case of monoclonal antibodies (mAbs), and due to their more complex
      structure, a greater level of demand would be in order and identity at other
      levels (e.g., post-translational modifications within the Fc region of the
      molecule) should be proved to establish "similarity". These requirements would
      lead to a greater development in the process and tighter quality controls during
      the production of biosimilar mAbs. The following issues should be taken into
      account in the comparability exercise: - The designs of the studies carried out
      to obtain approval of the reference product are not always adequate to show that
      safety and efficacy of the biosimilar mAbs are comparable. A similar efficacy
      does not necessarily imply a similar safety profile between the innovator and
      biosimilar products. - The design of clinical tests to demonstrate comparability
      must be flexible and adaptable throughout the development of the product. - The
      European Medicines Agency (EMA) will consider suitable goals in the evaluation of
      biosimilar mAbs for their approval (e.g., to specify whether their goal is to
      check similarity with the reference product or to show that the treatment is
      effective at a clinical level).

PMID- 22978328
TI  - Photodynamic molecular beacons triggered by MMP-2 and MMP-9: influence of the
      distance between photosensitizer and quencher onto photophysical properties and
      enzymatic activation.
AB  - Angiogenesis is a key step in the tumoral progression process. It is
      characterized by an over-expression of a number of matrix metalloproteinases
      (MMP). Among these MMPs, gelatinases (MMP-2 and MMP-9) are known to play a
      critical role in tumor angiogenesis and the growth of many cancers. Photodynamic
      Molecular Beacons (PMB) can be designed for cancer treatment by associating a
      chlorin-like photosensitizer and a black hole quencher linked by a gelatinase
      substrate peptide with the aim of silencing photosensitizer toxicity in non
      targeted cells and restore its toxicity only in surrounding gelatinases. This
      article provides a report on the synthesis and photophysical and biochemical
      studies of new families of PMB, using tetraphenylchlorin and a black hole
      quencher as a donor-acceptor pair, and MMP specific sequence (H-Gly-Pro-Leu-Gly
      Ile-Ala-Gly-Gln-Lys-OH or H-Pro-Leu-Gly-Leu-OH) to keep them in close proximity.
      Different spacers were used to evaluate the influence of the distance between the
      photosensitizer and the quencher on the photophysical properties and enzymatic
      activation of the PMB. Time-resolved quenching experiments were performed and
      FRET energy transfer could be observed. Photosensitizers' triplet state band in
      transient absorption disappears in PMB. However, even if both MMP-2 and MMP-9
      were found to efficiently cleave the peptide alone, no cleavage was observed for
      all PMB. Further studies would be required to assess the ability of the PMB
      constructs to retain the sensitivity of the peptide linker to be cleaved by
      matrix metalloproteinases.

PMID- 22978329
TI  - Update of peptides with antibacterial activity.
AB  - For many years a battle has been going on between bacteria and humans, with
      bacteria trying to survive against the antibiotics used by humans. Bacteria are
      found to be dominant in this battle since they can develop resistance. In fact,
      in the last decade multi-, extended- and pan-drug resistant bacteria have been
      isolated. On the other hand, the number of new antibiotics approved by the FDA
      has dramatically decreased during the last 20 years. Therefore, there is a
      desperate need for developing new types of antibacterial agents, where
      antimicrobial peptides may play an important role. This review provides an update
      of the recently identified antimicrobial peptides. Three valid approaches for
      developing a future antibacterial agent, as are the mechanisms of action as well
      as the in vitro and in vivo assays have been described in depth. In comparison to
      the antibacterial agents available at present, the targets for most of the
      antimicrobial peptides are not well known. However several proposals having been
      introduced for many antimicrobial peptides of different mechanisms of action,
      there still lies some uncertainty about their utility. Hundreds of antimicrobial
      peptides have been tested in vitro against all types of bacteria, but in this
      review we will highlight only those which have been tested against the most
      important Gram-positive and Gram-negative bacteria. The last step to get a
      potential antibiotic includes studies with an in vivo model. Therefore only
      antimicrobial peptides with good activity are tested that have been described in
      this review.

PMID- 22978330
TI  - Cervical vertebral stenosis associated with a vertebral arch anomaly in the
      Basset Hound.
AB  - OBJECTIVES: To report the clinical presentation, imaging characteristics,
      treatment results, and histopathological findings of a previously undescribed
      vertebral malformation in the Basset Hound. ANIMALS AND METHODS: Retrospective
      case series study. Eighteen Basset Hounds presented for evaluation of a suspected
      cervical spinal cord problem. All dogs underwent computed tomography myelography
      or magnetic resonance imaging of the cervical region. RESULTS: Thirteen male and
      5 female Basset Hounds between 6 months and 10.8 years of age (median: 1.4 years)
      were studied. Clinical signs varied from cervical hyperesthesia to nonambulatory
      tetraparesis. Imaging demonstrated a well-defined and smooth hypertrophy of the
      dorsal lamina and spinous process of >= 2 adjacent vertebrae. Although this bony
      abnormality could decrease the ventrodorsal vertebral canal diameter, dorsal
      midline spinal cord compression was predominantly caused by ligamentum flavum
      hypertrophy. The articulation between C4 and C5 was most commonly affected. Three
      dogs were lost to follow-up, 10 dogs underwent dorsal laminectomy, and medical
      management was initiated in 5 dogs. Surgery resulted in a good outcome with short
      hospitalization times (median: 4.5 days) in all dogs, whereas medical management
      produced more variable results. Histopathology confirmed ligamentum flavum
      hypertrophy and demonstrated the fibrocartilaginous nature of this anomaly.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Dorsal lamina and spinous process
      hypertrophy leading to ligamentum flavum hypertrophy should be included in the
      differential diagnosis of Basset Hounds with cervical hyperesthesia or
      myelopathy. Prognosis after decompressive surgery is favorable. Although a
      genetic component is suspected, additional studies are needed to determine the
      specific etiology of this disorder.

PMID- 22978332
TI  - Editorial: targeted therapy, targeted dosing and targeted delivery in oncology:
      where do we stand?

PMID- 22978331
TI  - Biases in long-term location memory in the real world.
AB  - The category adjustment (CA) approach to distortions in location memory has been
      largely documented in simplified lab-created spaces but minimally in navigable
      real-world environments. In the current paper, we extend the approach to a
      navigable real-world environment and specifically evaluate the assumption that
      long-term location memory may be retrievable despite errors in recall. Memory for
      the location of a fountain in a heavily navigated square on a university campus
      was tested by reproduction on a photograph of the square and then by a forced
      choice recognition test. While the recall data showed the standard bias, the
      recognition data revealed chance-level performance. The pattern of results
      suggests a possible difference between accessibility of working memories for
      locations within laboratory-created spaces and long-term memories for locations
      within complex navigable spaces. The results are discussed in terms of the CA
      model.

PMID- 22978333
TI  - 100% human monoclonal antibodies in oncology: hype or breakthrough?
AB  - Targeted therapies have dramatically modified treatment strategies in oncology
      since the early 2000's, especially for treating digestive cancers. These new
      biotherapies such as anti-VEGF (bevacizumab) or anti-EGFR (cetuximab) monoclonal
      antibodies have given oncologists new opportunities to use innovative treatment
      schedules or combinations with cytotoxics. Consequently, significant improvements
      in response rates, with trends to longer progression-free survival and/or overall
      survival have been achieved in patients with metastatic colorectal cancer (mCRC).
      Panitumumab is a novel, 100% human, anti-EGFR1 (HER1) antibody that has been
      approved in late 2007 for use as monotherapy in mCRC patients resistant to
      standard chemotherapy, provided that their tumor express EGFR and display wild
      type K-Ras status. Panitumumab has been recently further approved in combination
      with chemotherapy in mCRC patients. However, owing to the fact that its mechanism
      of action for targeting EGFR is similar to that of chimeric cetuximab, picturing
      the specificities in pharmacological and pharmacokinetic properties of this 100%
      human antibody could help the oncologists to better define their strategies at
      the bedside.

PMID- 22978334
TI  - Optimize administration protocol of capecitabine plus docetaxel combination in
      metastatic breast cancer patients.
AB  - Combining several cytotoxics is the current mainstay for treating breast cancer
      patients. The combination between capecitabine and docetaxel was found to be more
      efficient than capecitabine or docetaxel when both were used as single agents.
      However, the administration protocol for this combination has been empirically
      chosen from single-agent trials. Based on already available population analysis,
      we propose here to optimize the administration protocol of this association so as
      to enhance efficacy while limiting treatment-related toxicity. Efficacy
      parameters evaluated from population analysis using a disturbed tumor growth
      model and safety characteristics from the available databases evidenced that: 1)
      Docetaxel is more efficient than capecitabine at the start of the treatment, but
      becomes less efficient next because of acquisition of resistance; 2) Over a long
      period of time, capecitabine is better tolerated than docetaxel. These
      characteristics allowed the following recommendations for an optimized modality
      of combination: 1) The treatment has to be started at the maximum tolerated dose
      for docetaxel; this dose should be individualized right from the start of the
      second cycle of treatment; 2) In parallel, capecitabine has to be started at a
      dose lower than its maximum tolerated dose. 3) When docetaxel becomes less
      efficient than capecitabine because of resistance, docetaxel dose has to be
      reduced but not discontinued. 4) If adverse events show during the treatment, it
      is recommended to reduce docetaxel, rather than capecitabine dosage. Combining
      modeling and statistical analysis of clinical data permit to optimize combination
      treatments. This procedure could be extended to others treatments involving
      combination of several cytotoxics.

PMID- 22978335
TI  - Progress in strategies for dosage regimen individualization.
AB  - Several findings suggest that patient outcome would be improved with
      individualized doses. The aim of this paper is to describe major approaches,
      methods and underlying basic foundations implemented, in clinical practice, for
      dosage individualization. Also we propose a new method codified by kinetic
      nomograms as reliable alternative to traditional Bayesian methods. Clinical and
      simulation data were reported to evaluate performances of the proposed methods.
      Real examples of therapeutic drug monitoring were selected. Bayesian methods were
      used to individualize high-dose methotrexate rate infusion and amikacin dosage
      regimen, and kinetic nomograms to adjust sirolimus doses. 1) Using only few
      measurements, Bayesian method resulted in accurate estimates of individual
      pharmacokinetic parameters of high dose methotrexate infusion. Targeting a pre
      defined end-of-infusion level, infusion rate was individualized according to the
      previously obtained pharmacokinetic parameters. 2) With the same reasoning,
      individual pharmacokinetic parameters of amikacin were obtained by Bayesian
      estimation using three individual samples. Subsequent dosage adjustment allowed
      achievement of therapeutic goals at steady state. 3) Without computing individual
      pharmacokinetic parameters, nor using pharmacokinetic software, kinetic nomograms
      steered individual sirolimus blood levels within its therapeutic window with only
      two samples and in the first week after starting treatment. This contribution
      relates traditional Bayesian methods developed in 80's but not yet fully
      integrated in clinical context because of their complexity. The contribution
      focuses on recent developments based on population approaches, rendering the
      dosage adjustment methodology a simple and quick bedside application.

PMID- 22978336
TI  - Anticancer drugs in liposomal nanodevices: a target delivery for a targeted
      therapy.
AB  - For many years, nanocarriers have been investigated to modify pharmacokinetics
      and biodistribution of various active molecules. In the cancer domain, one of the
      biggest challenges still remains the improvement of the therapeutic index, often
      too low, for the majority of antitumor drugs. The application of nanotechnologies
      for the treatment and the diagnosis of cancers are nowadays currently developed,
      or under development, and liposomes play an important role in the history of
      nanodevices. Because of their high degree of biocompatibility, lipid nanosystems
      have been used to improve pharmacological profiles of various anticancer drugs
      otherwise discarded because of their low water solubility, poor bioavailability
      or either fragile and subjected to rapid biotransformations. This review aims at
      introducing an overview of the last 40 years of liposome researches until the
      last liposomal formulations commercially available or undergoing clinical trials.
      Liposome properties will be described, with a particular emphasis over the last
      generation of carriers appreciated for their active targeting characteristics.
      Researchers foresee a remarkable impact of nanotechnologies in the field of
      medicine; this review will try to summarize the main concepts over liposome
      domain, which can count on encouraging results as target therapy associated with
      targeted delivery.

PMID- 22978337
TI  - A new model for determining the MTD during phase-I trials in pediatric oncology.
AB  - The primary goal of phase I studies in oncology is to determine the MTD (Maximum
      Tolerated Dose) for a drug. This MTD is determined with respect to an accepted
      risk (usually 33%) to see a limiting toxity for patients. In this paper we
      propose a new mathematical model to determine the MTD. An important feature of
      this model is that the limiting toxicity can be formulated as a combination of
      several basic graded toxicities such as hematologic or neurological. Another
      feature is the possibility to take into account several patient covariates to
      individualize the determination of the MTD. The model is a bayesian model where
      some prior information has been considered. The model is expected to work better
      than traditional empirical schemes for determining the MTD because it uses at
      every step all the available information on patients, and adds some major
      improvements as compared with existing CRM strategies because it uses whole data
      made available, including low-grades toxicities. Finally the model has been
      validated with a retrospective data set on 17 patients from a phase I study on
      paclitaxel in pediatric oncology. Calculated MTDs for each patient were found to
      be markedly different than the doses actually given following a traditional dose
      escalation methodology. Results suggest that our new model provides a better and
      safer way to drive dose-escalation in phase-I trials as compared with traditional
      schemes.

PMID- 22978338
TI  - Targetting esophageal and gastric cancers with monoclonal antibodies.
AB  - Target therapies and notably monoclonal antibodies are currently being considered
      for esophageal, gastric, and gastroesophageal junction cancers. EGFR was found to
      be overexpressed in 60-86% of gastric or gastroesophageal tumors and in 50-70% of
      esophageal cancers. Cetuximab was shown to be a radiosensitizing agent in the
      treatment of ENT neoplasia. These results led to several phase II encouraging
      therapeutic trials evaluating the combination of cetuximab with radiochemotherapy
      in locally advanced esophageal cancers. Numerous encouraging phase II trials
      evaluating cetuximab combined with chemotherapy in patients with gastric
      adenocarcinoma or gastroesophageal junction cancer were reported. These promising
      results are still to be confirmed by the ongoing phase III trials. Several
      studies reported HER2 overexpression in gastric cancer (7-34%), which appeared to
      be associated with poorer prognosis. Trastuzumab is a monoclonal antibody
      directed against the extracellular HER2 domain. The international phase III trial
      known as ToGA (Trastuzumab for Gastric Cancer) aimed to determine the clinical
      efficacy and acceptable toxicity profile of trastuzumab in combination with first
      line chemotherapy in HER2-overexpressing gastric or gastroesophageal cancer.
      Angiogenesis is an essential step in the initial phase of tumorigenesis, and it
      is normally absent from healthy tissues except for particular physiological
      situations, such as wound healing. VEGF-A plays a role in endothelial growth and
      angiogenesis. Bevacizumab, a humanized monoclonal anti-VEGF-A antibody, is
      currently being studied for gastric cancer. The phase III AVAGAST study,
      evaluating bevacizumab in association with chemotherapy in advanced gastric
      adenocarcinoma, did not achieve its primary aim of improved OS in bevacizumab
      treated patients.

PMID- 22978340
TI  - Can targeted therapy be successful without metronomic scheduling?
AB  - In medical oncology, targeted therapy has emerged over the last decade, as the
      most promising strategy to fight cancer. In addition, a more complete
      understanding of tumor heterogeneity and pharmacology of the more conventional
      anti-cancer agents has led to development of metronomic chemotherapy (MC) (i.e. a
      more frequent administration of anticancer agents at lower doses then the usual
      maximally tolerated dose because it has been realized that time of exposure to an
      effective drug concentration is more important than simply the dose/m2 or kg.),
      Here, we discuss the nature of the specificity of targeted anti-cancer treatments
      and conclude that optimizing the schedule is an effective way to improve
      treatment selectivity.

PMID- 22978339
TI  - Polymorphisms to predict outcome to the tyrosine kinase inhibitors gefitinib,
      erlotinib, sorafenib and sunitinib.
AB  - Conventional chemotherapeutic regimens have limited impact against most solid
      tumors and deal with significant toxicity. During the last years novel anticancer
      treatments targeting specific molecules or genes involved in cancer development
      are being developed to improve outcome and reduce side-effects. In particular
      several tyrosine-kinase inhibitors (TKIs, gefitinib, erlotinib, sorafenib and
      sunitinib) have been approved for the treatment of different solid tumors. Their
      clinical activity has been related to different clinical and biological
      parameters, such as the EGFR-activating mutations for gefitinib and erlotinib.
      However, not all clinical outcomes, including tolerability, are explained, and
      the identification/ validation of novel biomarkers is a viable area of research.
      Germline polymorphisms can be easily assessed in blood samples, and polymorphisms
      in EGFR, AKT1 and ABCG2 have been correlated with outcome and toxicity in lung
      cancer patients given EGFR-TKIs therapies. However, there are several
      controversial findings, influenced by differences in study design/analysis, while
      the prognostic/predictive role of these polymorphisms still needs to be evaluated
      within prospective studies. More studies on the relationship of the genotype with
      drug pharmacokinetics and mechanism of action are also warranted. All these
      studies, as well as further development and application of novel technologies to
      decipher genetic alterations, might contribute to the validation of selected
      polymorphisms as molecular markers predictive of drug activity and help in the
      selection of TKIs best suited to the individual patient.

PMID- 22978341
TI  - Search for distinctive markers in DNT and cortical grade II glioma in children:
      same clinicopathological and molecular entities?
AB  - BACKGROUND: Dysembryoplastic Neuroepithelial Tumours (DNT) are benign brain
      lesions arising during childhood that are characterized by early onset partial
      seizures, no neurological deficit and cortical location. Pathological diagnosis
      is easy when the glioneuronal element is present. Its absence might lead to the
      diagnosis of non-specific DNT or low-grade glioma (LGG). OBJECTIVE: The aim of
      this retrospective study was to analyse clinicopathological and molecular
      features of a series of cortical tumours, in order to find diagnostic and
      prognostic markers to better custom treatment next. METHODS: Twenty four children
      with cortical neuroepithelial tumour were included. Clinical and radiological
      data were collected. Histological diagnosis was reviewed for all patients. 1p19q
      and p53 status were obtained by FISH and immunohistochemistry respectively. IDH1
      2 gene mutations were assessed by DNA sequencing. CGH-array was performed in 6/24
      samples. RESULTS: We recorded 13 DNT and 11 cortical LGG. Median age at surgery
      was 11.5 years. Overall survival was 100% and event-free survival at 10 years was
      70%. No tumour displayed chromosomal alteration or 1p19q deletion or p53
      expression. Only one patient with grade-II oligoastrocytoma had an IDH1 mutation.
      No statistical difference was found between the two populations in terms of age,
      sex, tumour location, type of surgical resection, disease progression and
      clinical status at last follow-up. Only the occurrence of septations on
      preoperative MRI was significantly associated with pathological features of DNT.
      CONCLUSION: Patients with DNT and cortical LGG share excellent outcome. Our
      genetic analysis could not distinguish DNT from LGG. In particular, CGH-array
      analysis was strictly normal in both tumor types. In attempt to find molecular
      markers, diagnosis of these lesions remains difficult when the glioneuronal
      element is lacking.

PMID- 22978342
TI  - Genetic polymorphisms of drug metabolizing enzymes and transporters: the long way
      from bench to bedside.
AB  - Pharmacogenetics has progressively become a major concern in personalized
      medicine. The development of modern technologies in genetic testing and cost
      effectiveness have rendered genotyping strategies easy to perform comparing to
      time-consuming phenotyping methods. In oncology, canonical markers such TPMT,
      DPYD or UGT1A1 are routinely included in clinical practice but their use is still
      controversial partly because of insufficient genotype to phenotype correlation.
      The next challenge is to accurately translate genotype-phenotype correlations
      into clinically useful diagnostics, and clinically useful leads concerning new
      therapeutic targets. Besides, recent studies have focused on emerging genetic
      variants of ADME genes such cytidine deaminase (CDA) or pregnane X receptor (PXR)
      that could be of interest for predicting anticancer drug response or toxicity.
      The candidate gene approach "metabolism guided" now evolves towards more global
      strategies thanks to genome resequencing projects such HapMap that have
      considerably increased our knowledge of genetics variations in humans.
      Multiplexed genotyping methods make possible the set-up of panels of candidate or
      tag SNPs for subsequent haplotypic analysis. Last, genome-wide association
      studies (GWAS) are feasible when large cohort of patients is available to
      identify new loci associated with drug response or adverse drug reactions or to
      definitively confirm the role of candidate genetic variations.

PMID- 22978343
TI  - Population pharmacokinetic analysis of 5-FU and 5-FDHU in colorectal cancer
      patients: search for biomarkers associated with gastro-intestinal toxicity.
AB  - PURPOSE: The anticancer drug 5-fluorouracile (5-FU) which is indicated for the
      treatment of a variety of solid malignancies such as colorectal, breast, head and
      neck neoplasms is extensively biotransformed to 5 fluoro-5,6- dihydrouracil (5
      FDHU) by the dihydropyrimidine deshydrogenase enzyme (DPD). DPD deficiency is
      recognized as an important risk factor, predisposing patient to undergo
      severe/lethal toxicities. To date, relationships between 5-FU, 5- FDHU and
      toxicity following i.v. bolus administration has not been studied using the
      population pharmacokinetics approach. METHODS: Retrospective pharmacokinetic data
      of 5-FU and 5-FDHU from 127 colorectal cancer patients were used for the
      population pharmacokinetic analysis. Treatment schedule consisted of an adjuvant
      therapy with 5-FU plus leucovorin. 5- FU and 5-FDHU complete plasma profiles
      recorded on day-1 of the first chemotherapy cycle were modeled simultaneously
      using NONMEM software. Gastro-intestinal adverse events graded according to the
      WHO criteria were recorded after the first cycle. A population logistic
      regression model was developed to identify predictive factors of these adverse
      events. RESULTS: A three-compartment pharmacokinetic mixture model best described
      5-FU and 5-FDHU kinetics profiles. Linear and saturated elimination from the
      central compartment of 5-FU and a linear elimination from the 5-FDHU compartment
      were used. A bimodal distribution of the inter-compartmental clearance was
      observed allowing two subpopulation with high (17 L/h) and low values (3.35 L/h).
      DPD-phenotype is suspected to explain this mixture. No covariates were introduced
      in the final model. Also, no relationship was found between maximal metabolism
      rate and DPD-phenotype. Predictive factors associated with occurrence of high
      grade gastro-intestinal adverse events were gender, dose and lean body mass
      suggesting serious cautions with the BSA-weighted dose for women. For the low
      grade toxicities, 5-FU area under curve was predictive for woman and 5-FDHU area
      under curve for men. CONCLUSION: A population pharmacokinetic mixture model was
      developed to describe kinetic profiles of 5-FU and its major metabolite. This
      model has significant implications, to identify patients with potentially low DPD
      phenotype requiring earlier adjustment of the 5-FU dose. Also this analysis
      highlights the need for developing alternative dosing-scheme for women.

PMID- 22978344
TI  - Colonization of the oral cavity by yeasts in patients with chronic renal failure
      undergoing hemodialysis.
AB  - OBJECTIVES: To determine the frequency of yeast in the oral cavity of patients
      with chronic renal failure, undergoing hemodialysis (PCRFH); identification and
      antifungal susceptibility profile of yeast and demographic profile of patients.
      METHODS: We performed mouthwash in 146 PCRFH; the rinse fluid was collected and
      cultured, yeasts grown were identified by phenotypic and molecular methods. The
      antifungal susceptibility profile was determined against nystatin, amphotericin
      B, fluconazole, voriconazole, and caspofungin based in Clinical and Laboratory
      Standards Institute (document M27-A3). RESULTS: Positive culture was observed in
      39% of patients, of whom 53% were women; the median of dialysis time was 2.9
      years. The age of the colonized patients varied between 26 and 84 years, with a
      median of 52.5 years. PCRFH over 45 years were significantly more colonized (P =
      0.0108) as well as denture wearers (84.0%). We isolated 81 yeasts, predominantly
      Candida albicans (63%) followed by Candida glabrata. In general, yeasts were
      sensitive to the evaluated antifungal agents, but there was significant variation
      in the minimum inhibitory concentration, especially among non-C. albicans Candida
      (NCAC) compared to fluconazole, caspofungin, and amphotericin B. NCAC required
      significantly higher concentrations of fluconazole (P < 0.01). CONCLUSION: The
      rate of colonization by yeasts in PCRFH was high, and there was variability in
      species distribution and antifungal susceptibility profile. These results are
      little known in this group of patients and are important for controlling the risk
      of developing invasive fungal infections.

PMID- 22978345
TI  - RhinAsthma patient perspective: a short daily asthma and rhinitis QoL assessment.
AB  - BACKGROUND: The present study aimed to develop a short validated patient
      completed questionnaire, the RhinAsthma Patient Perspective (RAPP), to assess the
      health-related quality of life (HRQoL) in patients with asthma and comorbid
      allergic rhinitis in clinical practice. METHODS: A provisional RAPP questionnaire
      was formed from candidate items identified through retrospective analysis of 333
      RHINASTHMA questionnaires. This was then tested on 150 asthma patients with
      allergic rhinitis. RESULTS: Psychometric analyses identified eight items fitting
      a unidimensional model to form RAPP. Internal consistency (Cronbach's alpha
      coefficient > 0.8) and agreement with RHINASTHMA (r = -0.31, P = 0.0001) were
      excellent. Criterion, discriminant, and convergent validity were good.
      Reliability in 47 stable patients was very good (intra-class and concordance
      correlation coefficients were 0.90 and 0.89, respectively). Responsiveness in 103
      patients with health improvement or deterioration was significantly associated
      with changes in Global Rating Scale (r = -0.4965, P < 0.01), Rhinitis Visual
      Analogue Scale (r = 0.5722, P < 0.01) and asthma control test (r = -0.6483, P <
      0.01). Minimal clinical difference in the analyzed population was 2. CONCLUSION:
      RhinAsthma Patient Perspective is a simple eight-question questionnaire with good
      measurement properties and sensitivity to health changes, which will provide a
      valid, reliable and standardized HRQoL measurement in patients with asthma and
      comorbid allergic rhinitis in clinical practice.

PMID- 22978346
TI  - The promise of mTOR inhibitors in the treatment of colorectal cancer.
AB  - INTRODUCTION: Recently, deregulation of protein synthesis has begun to gain
      attention as a major player in cancer development and progression. Specifically,
      deregulation of the process of translation initiation appears to play a key role
      in oncogenesis. The PI3K/Akt/mTOR pathway is vital for cellular metabolism,
      growth and proliferation and thus an attractive therapeutic target in oncology.
      Accordingly, several mTOR inhibitors are currently being tested in many cancers
      including colorectal cancer (CRC). AREAS COVERED: In this review, the key
      components of the PI3K/Akt/mTOR pathways, their molecular alterations and the
      inhibitors targeting the mTOR pathway in CRC are described. Complex interactions
      with other pathways such as the MAPK pathway are analyzed, as are possible drug
      combinations that target this pathway. In addition, novel strategies for use of
      mTOR pathway inhibitors in CRC treatment are introduced. EXPERT OPINION: Clinical
      trials of mTOR inhibitors have been investigated in CRC. mTOR inhibitors may
      represent an attractive antitumor target in combination with strategies to target
      other pathways that may overcome resistance. Further research is needed to
      identify critical molecular effector mechanisms, molecular markers that predict
      responsiveness and potential toxicities.

PMID- 22978347
TI  - Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -a
      study of the OVCAD consortium.
AB  - BACKGROUND: The role of the tumor necrosis factor receptor associated protein 1
      (TRAP1) - supposed to be involved in protection of cells from apoptosis and
      oxidative stress - has just started to be investigated in ovarian cancer. TRAP1
      has been shown to be estrogen up-regulated in estrogen receptor alpha (ERalpha)
      positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far
      and the significance of ERalpha expression as therapeutic and prognostic marker
      is still controversial. Therefore, we investigated the importance of TRAP1
      together with ERalpha in regard to clinicopathological parameters, chemotherapy
      response, and survival. METHODS AND RESULTS: Expressions of TRAP1 and ERalpha
      were evaluated by immunohistochemical staining of tissue microarrays comprised of
      208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERalpha was
      expressed in 52% of all cases. High TRAP1 expression correlated significantly
      with ERalpha (p<0.001) but high TRAP1 expression was also found in 42% of ERalpha
      negative cases. High TRAP1 expression correlated significantly with favorable
      chemotherapy-response (HR = 0.48; 95%CI 0.24-0.96, p=0.037) and showed a
      significant impact on overall survival (OS) (HR = 0.65; 95%CI 0.43-0.99, p =
      0.044). ERalpha expression was a favorable prognostic factor for OS in univariate
      and multivariate analyses. Interestingly, the combined pattern (ERalpha positive
      and/or TRAP1-high) revealed the strongest independent and significant positive
      influence on OS (HR=0.41; 95%CI 0.27-0.64). CONCLUSION: Immunohistochemical
      evaluation of TRAP1 together with ERalpha provides significant prognostic
      information. TRAP1 alone is significantly associated with chemotherapy response
      and overall survival, rendering TRAP1 as interesting scientific and therapeutic
      target.

PMID- 22978349
TI  - Elucidating the mechanism of multiferroicity in (NH4)3Cr(O2)4 and its tailoring
      by alkali metal substitution.
AB  - The antiferromagnetic Cr(V) peroxychromates, M(3)Cr(O(2))(4), M = K, Rb, and Cs,
      become ferroelectric when mixed with NH(4)(+), but the underlying mechanism is
      not understood. Our dielectric relaxation, Raman scattering, and high-frequency
      EPR measurements on the M(3-x)(NH(4))(x)Cr(O(2))(4) family clarify this
      mechanism. At 295 K, (NH(4))(3)Cr(O(2))(4) is tetragonal (I42m), with the
      NH(4)(+) ions occupying two distinctly different sites, N1 and N2. A
      ferroelectric transition at T(c1) = 250 K is revealed by lambda-type anomalies in
      C(p) and dielectric constant, and lowering of symmetry to Cmc2(1). Below T(c1),
      the N1 sites lose their tetrahedral symmetry and thus polarization develops.
      Raman detection of translational modes involving the NH(4)(+) ions around 193 cm(
      1) supports this model. EPR around T(c1) revealed that the [Cr(O(2))(4)](3-) ions
      reorient by about 10 degrees . A minor peak at T(c2) ~ 207 K is attributed to a
      short-range ordering that culminates in a long-range, structural order at T(c3) ~
      137 K. At T(c3), the symmetry is lowered to P1 with significant changes in the
      cell parameters. Rb(+) and Cs(+) substitutions that block the N1 and N2 sites
      selectively show that T(c1) is related to the torsional motion of the N1 site,
      while T(c2) and T(c3) are governed by the motional slowing down of the N2 site.
      These data show that the multiferroic behavior of this family is governed by the
      rotational and translational dynamics of the NH(4)(+) ions and is tunable by
      their controlled substitutions. Relevance to other classes of possible
      multiferroics is pointed out.

PMID- 22978348
TI  - Cytomegalovirus infection during immunosuppressive therapy for diffuse
      parenchymal lung disease.
AB  - BACKGROUND AND OBJECTIVE: Cytomegalovirus (CMV) infection is a life-threatening
      condition in patients with diffuse parenchymal lung diseases (DPLDs), who are
      receiving immunosuppressive therapy. The aim of this study was to describe the
      clinical features of CMV infection and to propose a strategy for managing CMV
      infection in patients with DPLD who are receiving immunosuppressive therapy.
      METHODS: A retrospective longitudinal observational study was performed on 69
      patients with DPLDs (39 with acute/subacute onset, 30 with chronic onset) who
      were receiving immunosuppressive therapy and were positive for CMV pp65 antigen
      (CMV-pp65Ag) in peripheral blood leukocytes (PBLs). RESULTS: Clinical CMV disease
      and subclinical CMV antigenaemia developed in 23 and 46 patients, respectively.
      The cut-off level of CMV-pp65Ag indicating clinical CMV disease, as determined by
      receiver operator characteristic curve analysis, was 7.5 cells per 5 * 10(4)
      PBLs. Multivariate analysis revealed that early CMV infection was associated with
      acute/subacute onset of underlying DPLD and with respiratory dysfunction at the
      commencement of immunosuppressive therapy. Multivariate analysis also suggested
      that the acute/subacute onset of underlying DPLD, a CMV-pp65Ag titre of >7.5
      cells per 5 * 10(4) PBLs, and C-reactive protein levels >= 10 mg/L indicated a
      poor prognosis. CONCLUSIONS: We recommend that CMV-pp65Ag antigenaemia of >7.5
      cells per 5 * 10(4) PBLs in patients with DPLD should be treated with
      ganciclovir. Patients with lower levels of CMV-pp65Ag antigenaemia should be
      closely monitored or treated with ganciclovir if the clinical findings suggest a
      poor prognosis.

PMID- 22978350
TI  - Response to the comments from Drs Shimazawa and Ikeda.

PMID- 22978351
TI  - Factors associated with severe disease from malaria, pneumonia and diarrhea among
      children in rural Tanzania - a hospital-based cross-sectional study.
AB  - BACKGROUND: Mild cases of malaria, pneumonia and diarrhea are readily treatable
      with complete recovery and with inexpensive and widely available first-line
      drugs. However, treatment is complicated and expensive, and mortality is higher
      when children present to the hospital with severe forms of these illnesses. We
      studied how care seeking behaviours and other factors contributed to severity of
      malaria, pneumonia and diarrhoea among children less than five years in rural
      Tanzania. METHODS: We interviewed consecutive care-takers of children diagnosed
      with malaria, pneumonia and/or diarrhea at Korogwe and Muheza district hospitals,
      in north-eastern Tanzania, between July 2009 and January 2010, and compared
      characteristics of children presenting with severe and those with non-severe
      disease. RESULTS: A total of 293 children with severe and 190 with non-severe
      disease were studied. We found persistent associations between severity of
      disease and caretaker's lack of formal education (OR 6.6; 95% confidence interval
      (CI) 2.7-15.8) compared to those with post-primary education, middle compared to
      high socio-economic status (OR 1.9; 95% CI 1.2-3.2), having 4 or more children
      compared to having one child (OR 2.5; 95% CI 1.4-4.5), having utilized a nearer
      primary health care (PHC) facility for the same illness compared to having not
      (OR 5.2; 95% CI 3.0-9.1), and having purchased the first treatment other than
      paracetamol from local or drug shops compared to when the treatment was obtained
      from the public hospitals for the first time (OR 3.2; 95% CI 1.9-5.2). The old
      officially abandoned first line anti-malaria drug Sulfadoxin-pyrimethamine (SP)
      was found to still be in use for the treatment of malaria and was significantly
      associated with childrens' presentation to the hospital with severe malaria (OR
      12.5; 95% CI 1.6-108.0). CONCLUSIONS: Our results indicate that caretakers with
      no formal education, with lower SES and with many children can be target groups
      for interventions in order to further reduce child mortality from treatable
      illnesses. Furthermore, the quality of the available drug shops and PHC
      facilities need to be closely monitored.

PMID- 22978352
TI  - A thready affair: linking fungal diversity and community dynamics to terrestrial
      decomposition processes.
AB  - Filamentous fungi are critical to the decomposition of terrestrial organic matter
      and, consequently, in the global carbon cycle. In particular, their contribution
      to degradation of recalcitrant lignocellulose complexes has been widely studied.
      In this review, we focus on the functioning of terrestrial fungal decomposers and
      examine the factors that affect their activities and community dynamics. In
      relation to this, impacts of global warming and increased N deposition are
      discussed. We also address the contribution of fungal decomposer studies to the
      development of general community ecological concepts such as diversity
      functioning relationships, succession, priority effects and home-field advantage.
      Finally, we indicate several research directions that will lead to a more
      complete understanding of the ecological roles of terrestrial decomposer fungi
      such as their importance in turnover of rhizodeposits, the consequences of
      interactions with other organisms and niche differentiation.

PMID- 22978353
TI  - The role of aggressions suffered by healthcare workers as predictors of burnout.
AB  - AIMS AND OBJECTIVES: To examine the prevalence of aggression against healthcare
      professionals and to determine the possible impact that violent episodes have on
      healthcare professionals in terms of loss of enthusiasm and involvement towards
      work. The objective was to analyse the percentage of occupational assault against
      professionals' aggression in different types of healthcare services,
      differentiating between physical and verbal aggression as a possible variable in
      detecting burnout in doctors and nursing professionals. BACKGROUND: Leiter and
      Maslach have explored a double process model of burnout not only based on
      exhaustion by overload, but also based on personal and organisational value
      conflicts (community, rewards or values). Moreover, Whittington has obtained
      conclusive results about the possible relationship between violence and burnout
      in mental health nurses. DESIGN: A retrospective study was performed in three
      hospitals and 22 primary care centres in Spain (n = 1.826). METHODS: Through
      different questionnaires, we have explored the relationship between aggression
      suffered by healthcare workers and burnout. RESULTS: Eleven percent of
      respondents had been physically assaulted on at least one occasion, whilst 34.4%
      had suffered threats and intimidation on at least one occasion and 36.6% had been
      subjected to insults. Both forms of violence, physical and non-physical
      aggression, showed significant correlations with symptoms of burnout (emotional
      exhaustion, depersonalisation and inefficacy). CONCLUSIONS: The survey showed
      evidence of a double process: (1) by which excess workload helps predict burnout,
      and (2) by which a mismatch in the congruence of values, or interpersonal
      conflict, contributes in a meaningful way to each of the dimensions of burnout,
      adding overhead to the process of exhaustion-cynicism-lack of realisation.
      Relevance to clinical practice.  Studies indicate that health professionals are
      some of the most exposed to disorders steaming from psychosocial risks and a high
      comorbidity: anxiety, depression, etc. There is a clear need for accurate
      instruments of evaluation to detect not only the burnout but also the areas that
      cause it. Professional exhaustion caused by aggression or other factors can
      reflect a deterioration in the healthcare relationship.

PMID- 22978354
TI  - Recommendations for improving the end-of-life care system for homeless
      populations: A qualitative study of the views of Canadian health and social
      services professionals.
AB  - BACKGROUND: Homeless populations have complex and diverse end-of-life care needs.
      However, they typically die outside of the end-of-life care system. To date, few
      studies have explored barriers to the end-of-life care system for homeless
      populations. This qualitative study involving health and social services
      professionals from across Canada sought to identify barriers to the end-of-life
      care system for homeless populations and generate recommendations to improve
      their access to end-of-life care. METHODS: Semi-structured qualitative interviews
      were conducted with 54 health and social services professionals involved in end
      of-life care services delivery to homeless persons in six Canadian cities
      (Halifax, Hamilton, Ottawa, Thunder Bay, Toronto and Winnipeg). Participants
      included health administrators, physicians, nurses, social workers, harm
      reduction specialists, and outreach workers. Interviews were audio-recorded,
      transcribed verbatim and analysed thematically. RESULTS: Participants identified
      key barriers to end-of-life care services for homeless persons, including: (1)
      insufficient availability of end-of-life care services; (2) exclusionary
      operating procedures; and, (3) poor continuity of care. Participants identified
      recommendations that they felt had the potential to minimize these barriers,
      including: (1) adopting low-threshold strategies (e.g. flexible behavioural
      policies and harm reduction strategies); (2) linking with population-specific
      health and social care providers (e.g. emergency shelters); and, (3)
      strengthening population-specific training. CONCLUSIONS: Homeless persons may be
      underserved by the end-of-life care system as a result of barriers that they face
      to accessing end-of-life care services. Changes in the rules and regulations that
      reflect the health needs and circumstances of homeless persons and measures to
      improve continuity of care have the potential to increase equity in the end-of
      life care system for this underserved population.

PMID- 22978355
TI  - A new lysozyme tyr54asn mutation causing amyloidosis in a family of Swedish
      ancestry with gastrointestinal symptoms.
AB  - Familial amyloidoses are a group of inherited disorders that cause deposition of
      misfolded amyloidogenic proteins in various tissues, resulting in organ
      dysfunction. Point mutations in the coding region of seven different genes are
      known to cause clinically significant systemic amyloid disease. We describe a new
      mutation in exon 2 of the lysozyme gene associated with amyloidosis (ALys) in a
      61-year-old woman with a 7-year history of non-bloody, watery diarrhea, and
      weight loss. Biopsies of the duodenum and stomach were positive for amyloid
      deposits in the lamina propria and blood vessels. Direct DNA sequencing of the
      lysozyme gene revealed a single base nucleotide transversion from T to A at the
      first position of codon 54, resulting in replacement of Tyr by Asn in the mature
      lysozyme protein (pTyr54Asn). Immunoblot analysis of amyloid fibrils extracted
      from a fat tissue sample confirmed lysozyme as the amyloid protein. Clinically,
      the phenotype associated with this lysozyme mutation featured chronic abdominal
      pain, diarrhea, weight loss, malabsorption, and sicca syndrome. There was no
      associated nephropathy as has been reported for other ALys mutations. We describe
      a new mutant lysozyme that presents with abdominal discomfort, diarrhea, weight
      loss, and sicca syndrome.

PMID- 22978356
TI  - Half-metallic ferromagnetism via the interface electronic reconstruction in
      LaAlO3/SrMnO3 nanosheet superlattices.
AB  - Spintronic devices are very important for future information technology. Suitable
      materials for such devices should have half-metallic properties with only one
      spin channel conducting. Nanostructures have played an important role in this
      aspect. Here, we report the realization of robust half-metallic ferromagnetism
      via the interface electronic reconstruction in artificial LaAlO(3)/SrMnO(3)
      nanosheet supperlattices. On the basis of first-principles density-functional
      calculations, we reveal an obvious electron transfer from the (LaO)(+) layer to
      the adjacent (MnO(2))(0) layer. And the partially occupied e(g) orbitals at the
      Mn sites can mediate a half-metallic state via a Zener double-exchange mechanism.
      On the other hand, for the superlattices with a (SrO)(0)/(AlO(2))(-) interface,
      hole transfer at the interface is identified. These transferred holes reside
      mainly at oxygen sites in SrMnO(3), leading to either the preserved G-type AFM
      ordering in pp-type superlattices or complex magnetic ordering in np-type
      superlattices. Interestingly, when these systems transit to ferromagnetic
      ordering by an external magnetic field, an obvious change of electronic state at
      the Fermi level is found, suggesting a large magnetoresistive effect therein. Our
      studies demonstrate the unique electric and magnetic properties arising from a
      magnetic ordering dependent charge transfer and electronic reconstruction at
      perovskite heterointerfaces, and their potential applications in spintronic
      devices.

PMID- 22978357
TI  - Effects of a computerized working memory training program on working memory,
      attention, and academics in adolescents with severe LD and comorbid ADHD: a
      randomized controlled trial.
AB  - BACKGROUND: Youths with coexisting learning disabilities (LD) and attention
      deficit hyperactivity disorder (ADHD) are at risk for poor academic and social
      outcomes. The underlying cognitive deficits, such as poor working memory (WM),
      are not well targeted by current treatments for either LD or ADHD. Emerging
      evidence suggests that WM might be improved by intensive and adaptive
      computerized training, but it remains unclear whether this intervention would be
      effective for adolescents with severe LD and comorbid ADHD. METHODS: A total of
      sixty 12- to 17-year olds with LD/ADHD (52 male, 8 female, IQ > 80) were
      randomized to one of two computerized intervention programs: working memory
      training (Cogmed RM) or math training (Academy of Math) and evaluated before and
      3 weeks after completion. The criterion measures of WM included auditory-verbal
      and visual-spatial tasks. Near and far transfer measures included indices of
      cognitive and behavioral attention and academic achievement. RESULTS: Adolescents
      in the WM training group showed greater improvements in a subset of WM criterion
      measures compared with those in the math-training group, but no training effects
      were observed on the near or far measures. Those who showed the most improvement
      on the WM training tasks at school were rated as less inattentive/hyperactive at
      home by parents. CONCLUSIONS: Results suggest that WM training may enhance some
      aspects of WM in youths with LD/ADHD, but further development of the training
      program is required to promote transfer effects to other domains of function.

PMID- 22978358
TI  - Bovine herpes virus type 1 induces apoptosis through Fas-dependent and
      mitochondria-controlled manner in Madin-Darby bovine kidney cells.
AB  - BACKGROUND: Bovine herpesvirus type 1 (BHV-1) is an important pathogen in cattle
      that is responsible for substantial economic losses. Previous studies suggest
      that BHV-1 may induce apoptosis in Madin-Darby bovine kidney (MDBK) cells via a
      mechanism only involving caspases and p53. However, the mechanism for BHV-1
      induced MDBK cell apoptosis still requires more research. METHODS: MDBK was used
      as a model to study the precise signaling pathways of apoptosis induced by BHV-1
      infection. RESULTS: BHV-1 infection activated a Fas/FasL-mediated apoptotic
      pathway, resulting in activation of caspase-8 and cleavage of Bid. In addition,
      BHV-1 infection down-regulated Bcl-2 and up-regulated Bax expression, thereby
      initiating the release of cytochrome c followed by caspase-9 activation. The
      combined activation of the extrinsic and intrinsic pathways resulted in
      activation of downstream effecter caspase-3 and poly ADP-ribose polymerase
      (PARP), leading to apoptosis. Furthermore, blocking apoptosis using caspase
      inhibitors improved BHV-1-infected MDBK cell viability to different extent. BHV-1
      infection did not induce significant DNA fragmentation in MDBK cells pretreated
      with ammonium chloride (NH4Cl) or cells infected with UV-inactivated BHV-1.
      Blocking caspases activation increased BHV-1 replication. CONCLUSIONS: BHV-1
      induces apoptosis in MDBK cells through extrinsic and intrinsic pathways and
      there might be cross-talk between the two pathways. In addition, BHV-1
      replication may be necessary for the induction of apoptosis in BHV-1-infected
      cells, and prolonged cell viability benefits BHV-1 replication.

PMID- 22978359
TI  - Renal hyperfiltration in prediabetes confirmed by fasting plasma glucose and
      hemoglobin A1c.
AB  - BACKGROUND: The aim of the study was to confirm that glomerular hyperfiltration,
      an early and reversible stage of kidney damage, is associated in patients with
      prediabetes and prehypertension. METHODS: In total, 5003 people aged between 35
      and 69 years who had participated in the Shizuoka part of the Japan Multi
      Institutional Collaborative Cohort (J-MICC) study took part in the study.
      Prevalence of hyperfiltration [the estimated glomerular filtration rate (eGFR)
      above the age- /sex-specific 95th percentile] was compared among different stages
      of prediabetes [fasting plasma glucose (FPG) < 100, 100-109, 110-125, and >=126
      mg/dL; and/or hemoglobin A1c (HbA1c) < 5.7, 5.7-6.0, 6.1-6.4 and >=6.5% for no
      prediabetes, stage 1 prediabetes, stage 2 prediabetes, and overt diabetes,
      respectively] and prehypertension (blood pressure <120/80, 120-129/80-84, 130
      139/85-89, and >=140/90 mmHg for no prehypertension, stage 1 prehypertension,
      stage 2 prehypertension, and overt hypertension, respectively). RESULTS: The
      prevalence of hyperfiltration increased with increasing stages of prediabetes
      (odds ratios: 1.25, 1.68, and 2.37 using FPG, and 1.26, 2.15, and 2.45 using
      HbA1c for stage 1 prediabetes, stage 2 prediabetes, and diabetes, respectively,
      relative to no prediabetes). Prehypertension, however, was not associated with
      hyperfiltration. CONCLUSION: The results confirmed that the prevalence of
      glomerular hyperfiltration increased with increasing stages (i.e., worsening) of
      prediabetes. Because both FPG and HbA1c showed similar association with
      hyperfiltration, either of these can be used to identify subjects who are at
      increased risk of nephropathy. Therefore, the functioning of kidneys should be
      monitored in subjects with prediabetes. Prompt treatment of hyperglycemia is
      necessary in subjects with hyperfiltration to prevent it to cause nephropathy.

PMID- 22978360
TI  - Unilateral renal venous thrombosis secondary to the use of vibration belt in a
      young woman.
AB  - We report on the isolated unilateral renal venous thrombosis (RVT) detected in a
      young patient who used vibration belt to stay thin. Apart from her sickle cell
      trait, the patient presented no other clinical situations associated with RVT.

PMID- 22978361
TI  - Posterior reversible encephalopathy syndrome in setting of postobstructive
      diuresis and persistent hypocalcemia.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiographic
      entity of heterogenous etiologies, which are grouped together because of similar
      findings on neuroimaging studies, associated with similar symptom complex of
      headache, vision loss, altered mentation, and seizures. In this report, we
      describe a case of PRES in setting of postobstructive diuresis in a 5-year-old
      male child, whose solitary functioning kidney was obstructed by a 1.6-cm radio
      opaque stone, who after percutaneous nephrostomy (PCN) diversion developed
      persistent hypocalcemia which persisted despite maximum replacement by iv calcium
      gluconate drip, and the child developed repeated generalized tonic clonic
      convulsions and became unconscious for 4 days. Computerized tomography (CT) scan
      of the brain showed typical hypodensities in bilateral occipitoparietal regions
      suggesting PRES. Ultimately, over a period of 4 days, his hypocalcemia could be
      corrected and the child was neurologically normal on the 5th day. CT scan of the
      brain after a month was free of any hypodensities.

PMID- 22978362
TI  - Comparative study on the inhibitory effects of alpha-tocopherol and radon on
      carbon tetrachloride-induced renal damage.
AB  - Since the 2011 nuclear accident in Fukushima, the effects of low-dose
      irradiation, especially internal exposure, are at the forefront of everyone's
      attention. However, low-dose radiation induced various stimulating effects such
      as activation of antioxidative and immune functions. In this study, we attempted
      to evaluate the quantitative effects of the activation of antioxidative
      activities in kidney induced by radon inhalation on carbon tetrachloride (CCl4)
      induced renal damage. Mice were subjected to intraperitoneal (i.p.) injection of
      CCl4 after inhaling approximately 1000 or 2000 Bq/m3 radon for 24 h, or
      immediately after i.p. injection of alpha-tocopherol (100, 300, or 500 mg/kg
      bodyweight). In case of renal function, radon inhalation at a concentration of
      2000 Bq/m3 has the inhibitory effects similar to alpha-tocopherol treatment at a
      dose of 300-500 mg/kg bodyweight. The activities of superoxide dismutase and
      catalase in kidneys were significantly higher in mice exposed to radon as
      compared to mice treated with CCl4 alone. These findings suggest that radon
      inhalation has an antioxidative effect against CCl4-induced renal damage similar
      to the antioxidative effects of alpha-tocopherol due to induction of
      antioxidative functions.

PMID- 22978363
TI  - Can phylogeny predict chemical diversity and potential medicinal activity of
      plants? A case study of Amaryllidaceae.
AB  - BACKGROUND: During evolution, plants and other organisms have developed a
      diversity of chemical defences, leading to the evolution of various groups of
      specialized metabolites selected for their endogenous biological function. A
      correlation between phylogeny and biosynthetic pathways could offer a predictive
      approach enabling more efficient selection of plants for the development of
      traditional medicine and lead discovery. However, this relationship has rarely
      been rigorously tested and the potential predictive power is consequently
      unknown. RESULTS: We produced a phylogenetic hypothesis for the medicinally
      important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and
      Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over
      100 species. We tested if alkaloid diversity and activity in bioassays related to
      the central nervous system are significantly correlated with phylogeny and found
      evidence for a significant phylogenetic signal in these traits, although the
      effect is not strong. CONCLUSIONS: Several genera are non-monophyletic
      emphasizing the importance of using phylogeny for interpretation of character
      distribution. Alkaloid diversity and in vitro inhibition of acetylcholinesterase
      (AChE) and binding to the serotonin reuptake transporter (SERT) are significantly
      correlated with phylogeny. This has implications for the use of phylogenies to
      interpret chemical evolution and biosynthetic pathways, to select candidate taxa
      for lead discovery, and to make recommendations for policies regarding
      traditional use and conservation priorities.

PMID- 22978364
TI  - Photoinactivation of Escherichia coli (SURE2) without intracellular uptake of the
      photosensitizer.
AB  - AIM: This study was performed to investigate the possibility to photodynamically
      inactivate Gram-negative bacteria without intracellular uptake of the
      photosensitizer. The efficiency of the photodynamic growth inhibition of
      Escherichia coli (SURE2) was proved in a comparative study of a neutral and a
      cationic photosensitizer. METHODS AND RESULTS: We used confocal laser scanning
      microscopy (CLSM) to investigate the uptake of the photosensitizer by the
      bacteria to show that both chlorin e(6)  and TMPyP are not accumulated in the
      cells. Fluorescence lifetime imaging (FLIM) and phototoxicity experiments were
      used to investigate the photodynamic inactivation of the Gram-negative bacteria.
      The phototoxicity experiments were carried out using a white light LED-setup to
      irradiate the bacterial suspensions. The viability of the bacteria was obtained
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. For
      the cationic TMPyP, photodynamic inactivation without intracellular uptake was
      observed, whereas for chlorin e(6)  such behaviour was not found. CONCLUSIONS: It
      was proven that in general, it is possible to photodynamically inactivate Gram
      negative bacteria without photosensitizer accumulation in the bacterial cells.
      This fact is especially interesting, considering that the development of
      resistances may be prevented, leaving the active components outside the
      bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: In a world with bacteria that
      gain the ability to withstand the effects of antibiotics and are able to transmit
      on these resistances to the next generation, it becomes necessary to develop new
      approaches to inhibit the growth of multi-resistant bacteria. The photodynamic
      inactivation of bacteria is based on a three-component system by which the growth
      of the bacterial cells is inhibited. The well-directed oxidative damage is
      initiated by visible light of a certain wavelength, which excites a nontoxic
      photoactive molecule, called photosensitizer. Its reaction with oxygen causes the
      generation of cytotoxic species like singlet oxygen, which is highly reactive and
      causes the inactivation of the growth of bacteria.

PMID- 22978365
TI  - Peptide conjugated phosphorodiamidate morpholino oligomers increase survival of
      mice challenged with Ames Bacillus anthracis.
AB  - Targeting bacterial essential genes using antisense phosphorodiamidate morpholino
      oligomers (PMOs) represents an important strategy in the development of novel
      antibacterial therapeutics. PMOs are neutral DNA analogues that inhibit gene
      expression in a sequence-specific manner. In this study, several cationic,
      membrane-penetrating peptides were conjugated to PMOs (PPMOs) that target 2
      bacterial essential genes: acyl carrier protein (acpP) and gyrase A (gyrA). These
      were tested for their ability to inhibit growth of Bacillus anthracis, a gram
      positive spore-forming bacterium and causative agent of anthrax. PPMOs targeted
      upstream of both target gene start codons and conjugated with the bacterium
      permeating peptide (RFF)(3)R were found to be most effective in inhibiting
      bacterial growth in vitro. Both of the gene-targeted PPMOs protected macrophages
      from B. anthracis induced cell death. Subsequent, in vivo testing of the PPMOs
      resulted in increased survival of mice challenged with the virulent Ames strain
      of B. anthracis. Together, these studies suggest that PPMOs targeting essential
      genes have the potential of being used as antisense antibiotics to treat B.
      anthracis infections.

PMID- 22978367
TI  - Ameliorative potential of alpha-ketoglutaric acid (AKG) on acute lung injuries
      induced by ammonia inhalation in rats.
AB  - INTRODUCTION: Toxicants such as ammonia, if inhaled, can damage respiratory tract
      leading to acute lung injury and pulmonary edema. Besides being a possible threat
      for the workers in chemical industry, easy availability and the toxic nature of
      ammonia may be used by terror groups for inflicting mass casualty among
      vulnerable population. In the present study, we have evaluated the therapeutic
      efficacy of alpha-ketoglutarate (AKG) to mitigate acute effects of ammonia on
      lung structure and antioxidant status in experimental animals. METHODS: Acute
      lung injury (ALI) models were developed by inhalation of aerosols of liquid
      ammonia in male Sprague Dawley rats. AKG (5%) respiratory fluid was inhaled by
      nebulization once daily for 5 days. Animals were euthanized and their blood
      samples were collected for hematology and serum biochemistry analysis. Total cell
      count, total protein (TP), lactate dehydrogenase (LDH), antioxidant enzyme
      activity (CAT, SOD, GSH), and malonaldialdehyde (MDA) formation were measured in
      bronchoalveolar lavage (BAL) fluid. RESULTS: Treatment with AKG showed
      significant lung protection by lowering the levels of total cell count, TP, LDH,
      superoxide dismutase (SOD), and MDA in BAL fluid. There was a marked increase in
      catalase (CAT) and glutathione (GSH) content of BAL fluid post-AKG inhalation.
      Histopathology of lung tissue correlated with cellular and biochemical findings
      indicate therapeutic efficacy of AKG against ammonia-induced lung injuries.
      CONCLUSIONS: The data suggest a possible therapeutic role of AKG inhalation
      against ammonia-induced structural and inflammatory changes in the lung.

PMID- 22978366
TI  - Why in vivo may not equal in vitro - new effectors revealed by measurement of
      enzymatic activities under the same in vivo-like assay conditions.
AB  - Does the understanding of the dynamics of biochemical networks in vivo, in terms
      of the properties of their components determined in vitro, require the latter to
      be determined all under the same conditions? An in vivo-like assay medium for
      enzyme activity determination was designed based on the concentrations of the
      major ionic constituents of the Escherichia coli cytosol: K(+), Na(+), Mg(2+),
      phosphate, glutamate, sulfate and Cl(-). The maximum capacities (V(max)) of the
      extracted enzymes of two pathways were determined using both this in vivo-like
      assay medium and the assay medium specific for each enzyme. The enzyme activities
      differed between the two assay conditions. Most of the differences could be
      attributed to unsuspected, pleiotropic effects of K(+) and phosphate. K(+)
      activated some enzymes (aldolase, enolase and glutamate dehydrogenase) and
      inhibited others (phosphoglucose isomerase, phosphofructokinase, triosephosphate
      isomerase, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase,
      phosphoglycerate mutase), whereas phosphate inhibited all glycolytic enzymes and
      glutamine synthetase but only activated glutamine 2-oxoglutarate
      amidotransferase. Neither a high glutamate concentration, nor macromolecular
      crowding affected the glycolytic or nitrogen assimilation enzymes, other than
      through the product inhibition of glutamate dehydrogenase by glutamate. This
      strategy of assessing all pathway enzymes kinetically under the same conditions
      may be necessary to avoid inadvertent differences between in vivo and in vitro
      biochemistry. It may also serve to reveal otherwise unnoticed pleiotropic
      regulation, such as that demonstrated in the present study by K(+) and phosphate.

PMID- 22978368
TI  - Thalidomide: features and potential significance in oral precancerous conditions
      and oral cancer.
AB  - BACKGROUND: Thalidomide was originally marked as a sedative and anti-emetic, but
      was withdrawn after severe teratogenic effects had been discovered. More recently
      it has been claimed to alleviate a wide range of inflammatory disorders and
      malignancies. Studies showed that thalidomide might play a role in the management
      of some oral premalignant conditions and its potential to be an adjunct in the
      prevention of oral cancer. AIM: The aim of this study is to summarize the
      characteristics and feasibility of thalidomide in the development and prevention
      of oral precancerosis, and to draw attentions of researchers to its therapeutic
      potential in oral cancer. METHODS: Databases were searched on the basis of PubMed
      and EMbase. Thalidomide associated with the oral lichen planus, chronic discoid
      lupus erythematosus (CDLE) and oral cancer were assessed. RESULTS: We have summed
      up the structure and pharmacokinetics of thalidomide, possible role of
      thalidomide in cancer prevention, as well as the recent data concerning its
      effects in prevention of oral premalignant conditions and potential for the
      treatment of oral cancer. CONCLUSIONS: Therapeutic effects of thalidomide in oral
      lichen planus and CDLE have been discussed by clinical trials. And increasing
      evidences from in vitro and in vivo experiments show that thalidomide is a
      promising anticancerous agent for oral cancer, which should be paid attention to.
      It is necessary to perform more studies and clinical trials of large sample size
      to clarify underlying mechanisms and demonstrate the potential roles of
      thalidomide in clinical routine management of oral diseases.

PMID- 22978369
TI  - IgE detection to alpha/beta/gamma-gliadin and its clinical relevance in wheat
      dependent exercise-induced anaphylaxis.
AB  - Wheat-dependent exercise-induced anaphylaxis (WDEIA) is characterized by
      anaphylactic reactions after wheat ingestion and physical exercise. IgE
      antibodies to recombinant omega(5) -gliadin are detectable in a majority of WDEIA
      patients, but other wheat allergens may also play a role in elicitation of WDEIA.
      Here, we performed a comprehensive analysis of IgE reactivity to different wheat
      proteins in 17 patients with confirmed WDEIA by ImmunoCAP research prototypes and
      a semi-quantitative microarray immunoassay with alpha/beta/gamma-gliadin, high
      molecular-weight (HMW) glutenin, alpha-amylase inhibitor (AAI) dimer, and wheat
      lipid transfer protein (LTP). By ImmunoCAP, IgE to recombinant omega(5) -gliadin
      was detectable in 14/17 patients (82%), to alpha/beta/gamma-gliadin in 82%
      including the three patients lacking IgE to omega(5) -gliadin, and to HMW
      glutenin in 59%. The microarray revealed specifically gamma-gliadin as the second
      most important allergen. These results demonstrate the additional diagnostic
      value of alpha/beta- and gamma-gliadin in particular in omega(5) -gliadin
      negative patients in the diagnosis of WDEIA.

PMID- 22978370
TI  - On the geometry of fluoroscopy views for cervical interlaminar epidural
      injections.

PMID- 22978371
TI  - Cerebral vasculitis associated with Schistosoma mansoni infection.
AB  - BACKGROUND: Cerebral involvement in schistosomiasis is not rare, but it is
      underdiagnosed because of the lack of clinical suspicion and the frequency of
      asymptomatic forms. Neurologic complications are generally supported by granuloma
      formation around ectopic eggs which have migrated to the brain. Moreover,
      vascular lesions and cerebral arteritis have been well documented in
      histopathological studies. Nevertheless, cerebral vasculitis in later stages of
      the Schistosoma mansoni infection have not yet been described in living subjects.
      CASE PRESENTATION: A 28-year-old french woman had a stroke linked with cerebral
      vasculitis, 6 monthes after returning from Burkina-Faso. At the same time, a S.
      mansoni disseminated infection was diagnosed. She suffered from a new stroke
      after undertaking praziquantel therapy, which lead us to associate the S. mansoni
      infection and cerebral vasculitis. CONCLUSION: This is the first report of such
      association, since cerebral vasculitis has never been described in later stages
      of the S. mansoni infection. Although the causal link between the two pathologies
      could not be proved, we suggest that S. mansoni is able to cause severe vascular
      damage in cerebral vessels. Schistosomiasis must be investigated in the event of
      a brain infarct in young people, particularly in patients originating or
      returning from an endemic area.

PMID- 22978372
TI  - Are there any differences in the regulations of personalized medicine among the
      USA, EU and Japan?

PMID- 22978373
TI  - District nurses' perceptions of the concept of delegating administration of
      medication to home care aides working in the municipality: a discrepancy between
      legal regulations and practice.
AB  - AIMS AND OBJECTIVES: To describe district nurses' perceptions of the concept of
      delegating medication management to unlicensed personnel working in municipal
      social care. BACKGROUND: The delegation of medical tasks involves responsibility
      and is regulated by law to avoid damage and injuries and to protect the patient.
      The delegation of the administration of medication is a multifaceted task. The
      delegating district nurse is responsible for the outcome and should also follow
      up the delegated task. DESIGN: A descriptive qualitative study, involving semi
      structured interviews and content analysis. METHODS: Twenty district nurses were
      interviewed. The interviews were audio taped. The data were collected from April
      2009-August 2010 and analysed using content analysis. RESULTS: The findings
      revealed that the statutes of delegation appear to be incompatible with practice,
      however, mostly due to lack of time. Communication between district nurses and
      home care aides, as well as tutoring, was regarded as important. The district
      nurses found it imperative to be available to the home care aides and made an
      effort to create a trusting atmosphere. CONCLUSIONS: District nurses cannot
      manage their workload without delegating the administration of medication in the
      present organisational model of health care and social care. The statutes
      regarding delegating medicine tasks are also cumbersome and difficult to
      incorporate for district nurses who are responsible for the delegation. RELEVANCE
      TO CLINICAL PRACTICE: The findings elucidate the current situation as regards
      district nurses and the need to delegate the administration of medication. Health
      care and social care for home-dwelling older patients, as well as statutes, needs
      to be evaluated and updated to meet and be prepared for the increasing demands of
      care.

PMID- 22978374
TI  - Beneficial effects of omega-3 fatty acids in the proteome of high-density
      lipoprotein proteome.
AB  - BACKGROUND: Omega-3 poly-unsaturated fatty acids (omega-3 PUFAs) have
      demonstrated to be beneficial in the prevention of cardiovascular disease,
      however, the mechanisms by which they perform their cardiovascular protection
      have not been clarified. Intriguingly, some of these protective effects have also
      been linked to HDL. The hypothesis of this study was that omega-3 PUFAs could
      modify the protein cargo of HDL particle in a triglyceride non-dependent mode.
      The objective of the study was to compare the proteome of HDL before and after
      omega-3 PUFAs supplemented diet. METHODS: A comparative proteomic analysis in 6
      smoker subjects HDL before and after a 5 weeks omega-3 PUFAs enriched diet has
      been performed. RESULTS: Among the altered proteins, clusterin, paraoxonase, and
      apoAI were found to increase, while fibronectin, alpha-1-antitrypsin, complement
      C1r subcomponent and complement factor H decreased after diet supplementation
      with omega-3 PUFAs. Immunodetection assays confirmed these results. The up
      regulated proteins are related to anti-oxidant, anti-inflammatory and anti
      atherosclerotic properties of HDL, while the down-regulated proteins are related
      to regulation of complement activation and acute phase response. CONCLUSIONS:
      Despite the low number of subjects included in the study, our findings
      demonstrate that omega-3 PUFAs supplementation modifies lipoprotein containing
      apoAI (LpAI) proteome and suggest that these protein changes improve the
      functionality of the particle.

PMID- 22978375
TI  - HIV providers' perceptions of and attitudes toward female versus male patients.
AB  - As a first step in understanding the role that health care providers may play in
      observed gender disparities in HIV care in the United States, we sought to
      examine whether HIV providers' perceptions of and attitudes toward female and
      male patients differ. We used data from the Enhancing Communication to Improve
      HIV Outcomes (ECHO) study, a multisite, cross-sectional study focused on the role
      of the patient-provider relationship in disparities in HIV care conducted from
      October 2006 to June 2007. Using separate scales, we assessed HIV providers'
      perceptions about their patients (e.g., intelligence, compliance, responsibility)
      as well as providers' attitudes toward their patients (e.g., like, respect,
      frustrate). We used multivariable linear regression with generalized estimating
      equations to compare provider scores for female and male patients. Our sample
      comprised 37 HIV providers and 317 patients. Compared with male patients, HIV
      infected females were less likely to be highly educated or employed, and more
      likely to report nonadherence to antiretroviral medications and depressive
      symptoms. In unadjusted and adjusted analyses, there was a significant difference
      in providers' perceptions of female and male patients, with providers having more
      negative perceptions of female patients. However, there was no significant
      difference in HIV providers' attitudes toward female and male patients in
      unadjusted or adjusted analyses. Further study is needed to elucidate the role of
      providers' perceptions and attitudes about female and male patients in observed
      gender disparities in HIV care.

PMID- 22978376
TI  - The roots of Atractylodes japonica Koidzumi promote adipogenic differentiation
      via activation of the insulin signaling pathway in 3T3-L1 cells.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a complex metabolic disorder characterized
      by insulin resistance and hyperglycemia. Peroxisome proliferator-activated
      receptor gamma (PPARgamma) is a key transcription factor and plays an important
      role in the regulation of genes involved in adipogenic differentiation, glucose
      metabolism and insulin signal transduction. METHODS: In this study, the effects
      of the root extract of Atractylodes japonica Koidzumi (Atractylodis Rhizoma Alba,
      ARA) on the differentiation of 3T3-L1 preadipocytes and the possible mechanism of
      glucose transport were investigated. 3T3-L1 cells were cultured with insulin and
      ARA extract. RESULTS: In 3T3-L1 cells, ARA extract significantly enhanced
      adipogenic differentiation and upregulated the expression of PPARgamma genes and
      protein in a dose-dependent manner. ARA also promoted glucose transport by
      increasing the glucose transporter 4 (GLUT-4), phosphatidylinositol 3-kinase
      (PI3K) and insulin receptor substrates-1 (IRS-1) levels. CONCLUSION: Our results
      suggest that ARA extract may be an attractive therapeutic agent for managing T2D
      via promoting the differentiation of adipocytes with the upregulation of
      PPARgamma levels and the activation of the insulin signaling pathway.

PMID- 22978377
TI  - One-pot five-component synthesis of spirocyclopenta[b]chromene derivatives and
      their acid-catalyzed rearrangement.
AB  - The reaction of the zwitterionic intermediate, generated in situ from either tert
      butylisocyanide or cyclohexylisocyanide and acetylenedicarboxylates, with 3
      cyanochromones is described, whereupon spirochromenofuran derivatives 5 or 6 were
      obtained in good yields. The subsequent acid-catalyzed rearrangement of the
      isolated 2-imino-spirochromenofurans 5 to 2-amino-spirochromenofurans 7 has also
      been studied. Rational mechanistic schemes for the formation of compounds 5, 6,
      and 7 are proposed. The structure elucidation of the products was accomplished by
      1D and 2D NMR experiments and confirmed by X-ray crystallographic analysis. Full
      assignment of all (1)H and (13)C NMR chemical shifts has been unambiguously
      achieved with the aid of DFT/GIAO calculations.

PMID- 22978378
TI  - High-temperature luminescence quenching of colloidal quantum dots.
AB  - Thermal quenching of quantum dot (QD) luminescence is important for application
      in luminescent devices. Systematic studies of the quenching behavior above 300 K
      are, however, lacking. Here, high-temperature (300-500 K) luminescence studies
      are reported for highly efficient CdSe core-shell quantum dots (QDs), aimed at
      obtaining insight into temperature quenching of QD emission. Through thermal
      cycling (yoyo) experiments for QDs in polymer matrices, reversible and
      irreversible luminescence quenching processes can be distinguished. For a variety
      of core-shell systems, reversible quenching is observed in a similar temperature
      range, between 100 and 180  degrees C. The irreversible quenching behavior varies
      between different systems. Mechanisms for thermal quenching are discussed.

PMID- 22978379
TI  - A novel sample preparation method using rapid nonheated saponification method for
      the determination of cholesterol in emulsified foods.
AB  - In this study, nonheated saponification was employed as a novel, rapid, and easy
      sample preparation method for the determination of cholesterol in emulsified
      foods. Cholesterol content was analyzed using gas chromatography with a flame
      ionization detector (GC-FID). The cholesterol extraction method was optimized for
      maximum recovery from baby food and infant formula. Under these conditions, the
      optimum extraction solvent was 10 mL ethyl ether per 1 to 2 g sample, and the
      saponification solution was 0.2 mL KOH in methanol. The cholesterol content in
      the products was determined to be within the certified range of certified
      reference materials (CRMs), NIST SRM 1544 and SRM 1849. The results of the
      recovery test performed using spiked materials were in the range of 98.24% to
      99.45% with an relative standard devitation (RSD) between 0.83% and 1.61%. This
      method could be used to reduce sample pretreatment time and is expected to
      provide an accurate determination of cholesterol in emulsified food matrices such
      as infant formula and baby food. PRACTICAL APPLICATION: A novel, rapid, and easy
      sample preparation method using nonheated saponification was developed for
      cholesterol detection in emulsified foods. Recovery tests of CRMs were
      satisfactory, and the recoveries of spiked materials were accurate and precise.
      This method was effective and decreased the time required for analysis by 5-fold
      compared to the official method.

PMID- 22978380
TI  - Chinese highly pathogenic porcine reproductive and respiratory syndrome virus
      exhibits more extensive tissue tropism for pigs.
AB  - BACKGROUND: The highly pathogenic porcine reproductive and respiratory syndrome
      virus (PRRSV) emerging in China exhibits high fatality to pigs. However, the
      mechanism related to the increased pathogenicity of the virus remains unclear. In
      the present study, the differences in tissue tropism between the highly
      pathogenic PRRSV strain (JXwn06) and the low pathogenic PRRSV strain (HB-1/3.9)
      were investigated using PRRSV-specific immunohistochemistry (IHC) staining to
      provide evidence for elucidating possible mechanism of the pathogenicity of
      Chinese highly pathogenic PRRSV. FINDINGS: IHC examination showed that PRRSV
      antigen in the tissues including spleen, tonsil, thymus, kidney, cerebellum,
      stomach, small intestine, large intestine, turbinal bone and laryngeal cartilage
      was positive in more pigs inoculated with JXwn06 than HB-1/3.9, and the tissues
      including trachea, esophagus, liver, mandibular gland and thyroid gland were
      positive for viral antigen in the pigs inoculated with JXwn06, but not in the
      pigs inoculated with HB-1/3.9. Meanwhile, we observed that epithelium in tissues
      including interlobular bile duct in liver, distal renal tubule of kidney,
      esophageal gland and tracheal gland were positive for viral antigen only in
      JXwn06-inoculated pigs, and epithelium of gastric mucosa and fundic gland, and
      intestinal gland were positive for viral antigen in both JXwn06- and HB-1/3.9
      inoculated pigs, using monoclonal antibodies to N and Nsp2 proteins. CONCLUSIONS:
      Taken together, these findings indicate that the highly pathogenic PRRSV JXwn06
      displays an expanded tissue tropism in vivo, suggesting this may contribute to
      its high pathogenicity to pigs.

PMID- 22978381
TI  - Comparative genomics of eukaryotic small nucleolar RNAs reveals deep evolutionary
      ancestry amidst ongoing intragenomic mobility.
AB  - BACKGROUND: Small nucleolar (sno)RNAs are required for posttranscriptional
      processing and modification of ribosomal, spliceosomal and messenger RNAs. Their
      presence in both eukaryotes and archaea indicates that snoRNAs are evolutionarily
      ancient. The location of some snoRNAs within the introns of ribosomal protein
      genes has been suggested to belie an RNA world origin, with the exons of the
      earliest protein-coding genes having evolved around snoRNAs after the advent of
      templated protein synthesis. Alternatively, this intronic location may reflect
      more recent selection for coexpression of snoRNAs and ribosomal components,
      ensuring rRNA modification by snoRNAs during ribosome synthesis. To gain insight
      into the evolutionary origins of this genetic organization, we examined the
      antiquity of snoRNA families and the stability of their genomic location across
      44 eukaryote genomes. RESULTS: We report that dozens of snoRNA families are
      traceable to the Last Eukaryotic Common Ancestor (LECA), but find only weak
      similarities between the oldest eukaryotic snoRNAs and archaeal snoRNA-like
      genes. Moreover, many of these LECA snoRNAs are located within the introns of
      host genes independently traceable to the LECA. Comparative genomic analyses
      reveal the intronic location of LECA snoRNAs is not ancestral however, suggesting
      the pattern we observe is the result of ongoing intragenomic mobility. Analysis
      of human transcriptome data indicates that the primary requirement for hosting
      intronic snoRNAs is a broad expression profile. Consistent with ongoing mobility
      across broadly-expressed genes, we report a case of recent migration of a non
      LECA snoRNA from the intron of a ubiquitously expressed non-LECA host gene into
      the introns of two LECA genes during the evolution of primates. CONCLUSIONS: Our
      analyses show that snoRNAs were a well-established family of RNAs at the time
      when eukaryotes began to diversify. While many are intronic, this association is
      not evolutionarily stable across the eukaryote tree; ongoing intragenomic
      mobility has erased signal of their ancestral gene organization, and neither
      introns-first nor evolved co-expression adequately explain our results. We
      therefore present a third model - constrained drift - whereby individual snoRNAs
      are intragenomically mobile and may occupy any genomic location from which
      expression satisfies phenotype.

PMID- 22978383
TI  - Therapeutic effects of valproate combined with lithium carbonate on MPTP-induced
      parkinsonism in mice: possible mediation through enhanced autophagy.
AB  - In order to investigate the mechanisms and therapeutic effects of valproate
      combined with lithium carbonate on mouse model of Parkinson's disease (PD), male
      C57BL/6 mice were injected into intraperitoneal with valproate (20 MUg/ml)
      combined with lithium carbonate (10 MUg/ml) for 7 days following 1-methyl-4
      phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) (30 mg/kg) administration, and the
      effects on motor function were analyzed. Immunohistochemistry and Western
      blotting were used to detect alterations in the expression of PD biomarkers,
      including tyrosine hydroxylase (TH), and the level of autophagy was evaluated by
      the detection of microtubule-associated protein light chain 3 (LC3). In addition,
      the levels of monoamine neurotransmitters were measured in the striatum using
      high performance liquid chromatography (HPLC). After MPTP exposure, all groups
      manifested decreased rolling bar latency and spontaneous activity, in addition to
      increased pole-climbing time. The combined treatment group exhibited a recovery
      of rolling bar latency and pole-climbing time. The number of dopaminergic neurons
      in the substantia nigra following MPTP treatment was higher in the combined
      treatment group compared with the positive control group (p = .003).
      Immunoreactivity for LC3 was higher in the combined treatment group than in the
      controls (p = .003). The concentrations of both striatal dopamine and the
      dopamine metabolite dihydroxyphenyl acetic acid (DOPAC) were decreased in both
      MPTP-treated groups compared with the controls. The loss of DOPAC was less severe
      in the combined treatment group relative to the positive control group (p =
      .001). Therefore, we infer that valproate combined with lithium carbonate can
      rescue dopaminergic neurons and ameliorate the loss of DOPAC following MPTP
      treatment, likely via activation of autophagic/lysosomal pathways.

PMID- 22978382
TI  - Inhibitory effect of carob (Ceratonia siliqua) leaves methanolic extract on
      Listeria monocytogenes.
AB  - In recent years, there has been great development in the search for new natural
      compounds for food preservation aimed at a partial or total replacement of
      currently popular antimicrobial chemicals. Carob (Ceratonia siliqua) offers a
      natural promising alternative for food safety and bioconservation. In this work,
      the methanolic extract of carob leaves (MECL) was tested for the ability to
      inhibit the growth of a range of microorganisms. MECL inhibited the growth of
      Listeria monocytogenes at 28.12 MUg/mL by the broth microdilution method. The
      effect of this bacteriostatic concentration on the growth of this bacterium
      revealed a pattern of inhibition characterized by (a) a resumed growth phase,
      which showed a lower rate of growth if compared with controls; and (b) first a
      lag and then a stationary phase at a lower bacterium concentration. The study of
      the chemical composition of MECL by high-performance liquid chromatography and
      liquid chromatography/mass spectrometry showed the presence of gallic acid, (-)
      epigallocatechin-3-gallate, myricitrin, isoquercitin, catechin, chlorogenic acid,
      and malic acid. L. monocytogenes growth inhibition was recorded for myricitrin
      and gallic acid at 450 MUg/mL and for (-)-epigallocatechin-3-gallate and
      isoquercitin, respectively, at 225 and 112.5 MUg/mL. Taking into account that
      proline is a ligand of proline dehydrogenase (PDH), the use of this compound
      leads us to hypothesize the mode of action of MECL constituents. 

PMID- 22978384
TI  - Impact of mild to moderate elevations of alanine aminotransferase on liver
      stiffness measurement in chronic hepatitis B patients during antiviral therapy.
AB  - AIM:   The accuracy of liver stiffness measurement (LSM) in the diagnosis of
      liver fibrosis is affected by elevated serum alanine aminotransferase (ALT)
      levels. The aim of this study was to assess the impact of mild to moderate
      elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during
      antiviral therapy. METHODS:   A total of 58 CHB patients with their ALT levels
      falling into the range of *2 to *10 the upper limit of normal (ULN) were
      recruited. ALT and LSM values were periodically assessed at baseline and 12, 24
      and 48 weeks. RESULTS:   The median ALT levels were 153.5 (76-544), 50.5 (11
      475), 36.5 (9-265) and 30 (12-239) IU/L at baseline and 12, 24 and 48 weeks,
      respectively. The corresponding median value of LSM was 8.8 (3.2-47.3), 6.15 (3.2
      31.2), 5.9 (3.1-29.1) and 5.5 (2.8-21.5) kpa. However, after the ALT levels were
      normalized by the treatment, the values of LSM did not vary significantly (6.1
      [3.0-17.7] vs 5.25 [2.8-21.5] kpa, P = 0.381). Pretreatment fibrosis stages of
      liver biopsies corresponded with LSM after ALT normalization rather than baseline
      LSM (F0-1, 12/27 vs 23/25, P < 0.001). CONCLUSION:   The LSM values decreased in
      parallel with the decline in ALT levels in CHB patients with mild to moderate
      elevation of ALT. LSM became more accurate when applied to document the liver
      fibrosis or cirrhosis in CHB patients after the elevated ALT level has been
      treated to normal level.

PMID- 22978386
TI  - A surprising observation that oxygen can affect the product enantiopurity of an
      enzyme-catalysed reaction.
AB  - Enzymes are natural catalysts, controlling reactions with typically high
      stereospecificity and enantiospecificity in substrate selection and/or product
      formation. This makes them useful in the synthesis of industrially relevant
      compounds, particularly where highly enantiopure products are required. The
      flavoprotein pentaerythritol tetranitrate (PETN) reductase is a member of the Old
      Yellow Enzyme family, and catalyses the asymmetric reduction of beta-alkyl-beta
      arylnitroalkenes. Under aerobic conditions, it additionally undergoes futile
      cycles of NAD(P)H reduction of flavin, followed by reoxidation by oxygen, which
      generates the reactive oxygen species (ROS) hydrogen peroxide and superoxide.
      Prior studies have shown that not all reactions catalysed by PETN reductase yield
      enantiopure products, such as the reduction of (E)-2-phenyl-1-nitroprop-1-ene
      (PNE) to produce (S)-2-phenyl-1-nitropropane (PNA) with variable enantiomeric
      excess (ee). Recent independent studies of (E)-PNE reduction by PETN reductase
      showed that the major product formed could be switched to (R)-PNA, depending on
      the reaction conditions. We investigated this phenomenon, and found that the
      presence of oxygen and ROS influenced the overall product enantiopurity.
      Anaerobic reactions produced consistently higher nitroalkane (S)-PNA product
      yields than aerobic reactions (64% versus 28%). The presence of oxygen
      dramatically increased the preference for (R)-PNA formation (up to 52% ee).
      Conversely, the presence of the ROS superoxide and hydrogen peroxide switched the
      preference to (S)-PNA product formation. Given that oxygen has no role in the
      natural catalytic cycle, these findings demonstrate a remarkable ability to
      manipulate product enantiopurity of this enzyme-catalysed reaction by simple
      manipulation of reaction conditions. Potential mechanisms of this unusual
      behaviour are discussed.

PMID- 22978385
TI  - The metabolic and toxicological considerations for immunosuppressive drugs used
      during pancreas transplantation.
AB  - INTRODUCTION: Pancreas-kidney transplant is an effective treatment for patients
      with insulin-dependent dabetes and chronic renal failure. Reduction in technical
      failure loss and early acute rejection rates contributed to prolong pancreas
      graft survival. However, drug toxicity affects negatively both short- and long
      term follow-ups. AREAS COVERED: This article reviews the existing literature and
      knowledge of the immunosuppressive drugs that are frequently used in pancreas
      transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and
      mycophenolate. The article also discusses the short- and long-term adverse
      effects of these drugs. The article also reports and discusses the most relevant
      in vitro studies, providing additional information to in vivo findings. Some
      clinically relevant drug interactions with immunosuppressive drugs are also
      highlighted. Over- and underimmunosuppression effects will not be addressed.
      EXPERT OPINION: Immunosuppressive regimen after pancreas transplant is very
      effective and contributed to pancreas allograft survival. However, they present
      several side effects that are potentiated when drugs are combined. Modifiable and
      non-modifiable risk factors can aggravate metabolic and toxicological effects of
      immunosuppressive drugs. It is important to critically analyze the results of
      clinical studies and investigate new immunosuppressive drugs and/or novel drug
      combinations. It is equally important to comprehend and interpret experimental
      data. Therefore, minimization of side effects, based on safe approaches, can
      prolong pancreas allograft survival.

PMID- 22978387
TI  - Clinical and immunophenotypic features of atypical complete DiGeorge syndrome.
AB  - BACKGROUND: DiGeorge syndrome is a congenital malformation characterized by
      variable defects of the thymus, heart and parathyroid glands. Athymic patients
      are classified as exhibiting complete DiGeorge syndrome. Some of these patients
      may also exhibit oligoclonal T-cell expansion, generalized rash and
      lymphadenopathy at some point after birth. This rare condition is known as
      atypical complete DiGeorge syndrome, resembles Omenn syndrome, and has not been
      fully characterized. METHODS: The clinical and immunophenotypic features of
      atypical complete DiGeorge syndrome were assessed in two affected Japanese
      infants. T-cell receptor (TCR) Vbeta repertoire was analyzed on flow cytometry
      and complementarity-determining region 3 spectratyping. RESULTS: Both patients
      had no detectable thymus tissue and profound T-cell lymphopenia soon after birth.
      Progressive increase of activated T cells, however, as well as eosinophilia, high
      serum IgE level, generalized rash, and lymphadenopathy were observed during early
      infancy. A highly restricted TCR Vbeta repertoire was demonstrated both in CD4(+)
      and CD8(+)  T cells. CONCLUSIONS: The Omenn syndrome-like manifestations might
      be associated with the oligoclonal proliferation of activated T cells. Analysis
      of the immunophenotype and TCR Vbeta repertoire is helpful to establish the early
      diagnosis of atypical complete DiGeorge syndrome.

PMID- 22978388
TI  - An unusual cribriform variant of salivary basal cell tumours: a
      clinicopathological study of 22 cases.
AB  - AIMS: To clarify the clinicopathological characteristics of salivary basal cell
      tumours exhibiting cribriform architecture, and to discuss the differential
      diagnosis of these tumours with regard to adenoid cystic carcinoma (AdCC).
      METHODS AND RESULTS: Eighteen basal cell adenomas (BCAs) and four basal cell
      adenocarcinomas (BcACs) with at least a 10% area of cribriform morphology were
      collected, and the histological and immunohistochemical features were evaluated.
      The majority of tumours showed the typical histological patterns of basal cell
      tumours, in addition to cribriform architecture. In some areas, the periphery of
      cribriform nests had a palisade arrangement. Focal capsular infiltration, but not
      invasion of surrounding normal tissue, was detected in 14 of 18 BCAs. The
      capsules were absent or incomplete and mainly accompanied by focal invasion in
      BcACs. Cystic degeneration was observed in 12 of 22 tumours. The Ki67 labelling
      index of basal cell tumours was significantly lower than that of cribriform AdCCs
      (P = 0.001). All patients had a good outcome after a follow-up of 15-96 months.
      CONCLUSIONS: The cribriform variant shares most of the clinicopathological
      features of conventional basal cell tumours. Admixtures of cribriform and
      trabecular or tubulo-trabecular subtypes, peripheral palisading, cystic changes,
      non-invasive or low-grade invasive growth patterns and a low Ki67 labelling index
      may be useful for distinguishing basal cell tumours with a cribriform
      architecture from AdCCs.

PMID- 22978389
TI  - Fiber-based all-solid-state flexible supercapacitors for self-powered systems.
AB  - All-solid-state flexible supercapacitors based on a carbon/MnO(2) (C/M) core
      shell fiber structure were fabricated with high electrochemical performance such
      as high rate capability with a scan rate up to 20 V s(-1), high volume
      capacitance of 2.5 F cm(-3), and an energy density of 2.2 * 10(-4) Wh cm(-3). By
      integrating with a triboelectric generator, supercapacitors could be charged and
      power commercial electronic devices, such as a liquid crystal display or a light
      emitting-diode, demonstrating feasibility as an efficient storage component and
      self-powered micro/nanosystems.

PMID- 22978390
TI  - Salivary markers of oxidative stress are related to age and oral health in adult
      non-smokers.
AB  - BACKGROUND: Salivary concentrations of thiobarbituric acid-reacting substances
      (TBARS) are associated with the periodontal status assessed as papillary bleeding
      index (PBI). Whether this association is age independent is currently unclear.
      Salivary concentrations of advanced oxidation protein products (AOPPs) and
      advanced glycation end products (AGEs) have not been assessed in relation to age
      or oral health yet. The aim of our study was to analyse salivary markers of
      oxidative stress in dental patients in relation to age, gender and oral health.
      METHODS: Consecutive adult non-smoking dental patients were enrolled (n = 204;
      aged 19-83 years). PBI and the caries index (CI) were assessed. Markers of
      oxidative stress, such as TBARS, AOPPs and AGEs, and the total antioxidant
      capacity (TAC) were measured in saliva samples taken before clinical examination.
      RESULTS: Linear regression showed that salivary TBARS, AGEs and TAC significantly
      increase with age (r squared = 5.3%, 2.1% and 5%, respectively). PBI is an
      independent predictor of salivary TBARS (r squared = 5.5%), and the CI negatively
      affected AOPPs (r = 3.2%) and positively affected TBARS (r = 2.5%). Gender did
      not affect any of the analysed parameters. CONCLUSIONS: Age as a significant
      contributor to the variance should be taken into account in studies focusing on
      salivary markers of oxidative stress. The relationship between PBI and salivary
      TBARS confirms results from previous studies. In addition, our results show that
      the association is age independent. Negative association between the CI and AOPPs
      might be related to recent findings that AOPP might be actually a marker of non
      enzymatic antioxidant status.

PMID- 22978391
TI  - Changes in body weight, composition, and shape: a 4-year study of college
      students.
AB  - The objectives of this study were to examine changes in body weight, body mass
      index (BMI), body composition, and shape in a group of male and female students
      over the 4-year college period. Anthropometric assessments including height and
      weight (via standard techniques), body composition (via bioelectrical impedance
      analysis), and body shape (via 3-dimensional body scanning) were conducted at the
      beginning of the freshman year and end of the senior year in 131 college
      students. Four-year changes included significant (p < 0.0001) gains in weight
      (3.0 kg), BMI (1.0 kg.m(-2)), body fat (3.6%), and absolute fat mass (3.2 kg).
      Males gained significantly (p < 0.0001) greater amounts of weight, BMI, percent
      and absolute fat mass, and fat-free mass than females. Weight change ranged from
      (-)8.7 to (+)16.8 kg. About 70% of the participants gained weight, which averaged
      5.3 kg; significant (p < 0.0001) gains in BMI, fat-free mass, absolute fat mass,
      and percent body fat and significant (p < 0.0005) increases in neck, chest-bust,
      waist, hips, seat, and biceps circumferences were also observed in this weight
      gain group. The percentage of participants classified as overweight-obese
      increased from 18% to 31%. The number of females and males with >=30% and 20%
      body fat, respectively, increased from n = 14 to n = 26 (with n = 4 exhibiting
      normal weight obesity) over the 4-year period. The waist circumference changes
      were significantly (p < 0.0001) correlated with both weight and percent body fat
      changes. In conclusion, the increasing prevalence of obesity and normal weight
      obesity among this college population suggests the need for additional health
      promotion strategies on college campuses.

PMID- 22978392
TI  - Fatty acids - induced lipotoxicity and inflammation.
AB  - Fatty acids are known to serve as energetic substrates, key components of
      membrane lipids, and as substrates for the synthesis of signaling molecules and
      complex lipids. They are also known to be ligands either of membrane receptors
      involved in cell signaling or of nuclear receptors mediating gene regulation.
      Accumulation of fatty acids due to altered metabolism and/or unbalanced diet has
      been described to be toxic for several tissues, especially liver. In numerous
      cell types, cell death, cytokine secretion and activation of inflammatory
      processes appear to be a consequence of fatty acid accumulation. This review
      presents the different classes of fatty acids known to trigger toxic effects and
      inflammation, the cellular and subcellular targets of these fatty acids in the
      context of non-alcoholic fatty liver disease (NAFLD), and the mechanisms by which
      these effects are mediated.

PMID- 22978393
TI  - Lipids and lysosomes.
AB  - Lysosomes are cytoplasmic organelles delimited by a single membrane and filled
      with a variety of hydrolytic enzymes active at acidic pH and collectively capable
      to degrade the vast majority of macromolecules entering lysosomes via
      endocytosis, phagocytosis or autophagy. In this review, we describe the lipid
      composition and the dynamic properties of lysosomal membrane, the main delivery
      pathways of lipids to lysosomes and their catabolism inside lysosomes. Then, we
      present the consequences of a lipid accumulation as seen in various lysosomal
      storage diseases on lysosomal functions. Finally, we discuss about the possible
      involvement of lysosomes in lipotoxicity.

PMID- 22978394
TI  - Mitochondrial dysfunction and lipid homeostasis.
AB  - This review is aimed at illustrating that mitochondrial dysfunction and altered
      lipid homeostasis may concur in a variety of pathogenesis states, being either
      contributive or consecutive to primary disease events. Underlying mechanisms for
      this concurrence are far from being the exhaustive elements taking place in
      disease development. They may however complicate, contribute or cause the
      disease. In the first part of the review, physiological roles of mitochondria in
      coordinating lipid metabolism and in controlling reactive oxygen species (ROS),
      ATP and calcium levels are briefly presented. In a second part, clues for how
      mitochondria-driven alterations in lipid metabolism may induce toxicity are
      discussed. In the third part, it is illustrated how mitochondrial dysfunction and
      lipid homeostasis disruption may be associated (i) to complicate type 1 diabetes
      (pancreatic beta-cell mitochondrial dysfunction in ATP yield induces reduced
      insulin secretion and hence disruption of glucose and lipid metabolism), (ii) to
      contribute to type 2 diabetes and other insulin resistant states (mitochondrial
      impairment may induce adipocyte dysfunction with subsequent increase in
      circulating free fatty acids and their abnormal deposit in non adipose tissues
      (pancreatic beta-cells, skeletal muscle and liver) which results in lipotoxicity
      and mitochondrial dysfunction), (iii) to offer new clues in our understanding of
      how the brain controls feeding supply and energy expenditure, (iv) to promote
      cancer development notably via fatty acid oxidation/synthesis imbalance (in favor
      of synthesis) further strengthened in some cancers by a lipogenetic benefit
      induced by a HER2/fatty acid synthase cross-talk, and (v) to favor cardiovascular
      disorders by impacting heart function and arterial wall integrity.

PMID- 22978395
TI  - Peroxisomes, peroxisomal diseases, and the hepatotoxicity induced by peroxisomal
      metabolites.
AB  - The group of peroxisomal disorders represents a growing number of genetically
      determined diseases in humans in which there is an impairment in one or more
      peroxisomal functions. The peroxisomal disorders are usually subdivided in two
      major subgroups including (1) the peroxisome biogenesis disorders (PBDs) and (2)
      the single peroxisomal enzyme deficiencies. Liver pathology is a frequent finding
      in patients affected by a peroxisomal disorder. This is not only true for
      patients affected by a PBD, but also for patients with a single enzyme defect in
      one of the metabolic pathways in which peroxisomes are involved. By comparing the
      different peroxisomal disorders, we provide evidence suggesting that the main
      hepatotoxic metabolites responsible for the liver pathology found in patients,
      are the bile acid synthesis intermediates di- and trihydroxycholestanoic acid
      (DHCA and THCA). Studies in different experimental systems have shown that DHCA
      and THCA, especially in the unconjugated form, interfere with different
      physiological processes including mitochondrial oxidative phosphorylation. The
      implications of these findings will be discussed with special emphasis on
      patients with di- and trihydroxycholestanoic acidaemia.

PMID- 22978396
TI  - Hepatic steatosis and peroxisomal fatty acid beta-oxidation.
AB  - Three subhepatocellular compartments concur for fatty acids degradation including
      omega-oxidation in endoplasmic reticulum and beta-oxidation in both mitochondria
      and peroxisomes. Deficits affecting the peroxisomal physiology may be associated
      with multiple metabolic disturbances. Nowadays, a growing body of evidence
      underlines the key role of peroxisomal beta-oxidation in the sensing of lipid
      metabolism through the production/degradation of some essential metabolites.
      Lessons from several mice models strengthen the link between fatty acid beta
      oxidation in peroxisomes and the nuclear hormone receptor Peroxisome Proliferator
      Activated Receptor (PPAR)-alpha with an additional level of coregualtor
      complexity, which couples regulation of body energetic balance and hepatic
      caloric flux to functional peroxisome status. Here, we review key determinants of
      disrupted peroxisomal beta-oxidation pathway, which in liver promotes hepatic
      steatosis and hepatocarcinogenesis.

PMID- 22978397
TI  - Nuclear receptors and transcription factors in the development of fatty liver
      disease.
AB  - Liver regulates certain key aspects of lipid metabolism including de novo
      lipogenesis, fatty acid oxidation, and lipoprotein uptake and secretion.
      Disturbances in these hepatic functions can contribute to the development of
      fatty liver disease. An understanding of the regulatory mechanisms influencing
      hepatic lipid homeostasis and systemic energy balance is therefore of paramount
      importance in gaining insights that might be useful in the management of fatty
      liver disease. In this regard, emerging evidence indicates that certain members
      of the nuclear receptor superfamily and some key transcription coactivators
      function as intracellular sensors to orchestrate hepatic lipid metabolism.
      Dysregulation of nuclear receptor-mediated transcriptional signaling and
      perturbations in the levels of their cognate endogenous ligands play a prominent
      role in the development of fatty liver disease. The potential of nuclear
      receptors, transcription coactivators as well as enzymes that participate in the
      synthesis and degradation of endogenous nuclear receptor ligands, as effective
      therapeutic targets for fatty liver disease needs evaluation.

PMID- 22978398
TI  - PPARalpha/HNF4alpha interplay on diversified responsive elements. Relevance in
      the regulation of liver peroxisomal fatty acid catabolism.
AB  - In mammals, the liver is the major organ of fatty acid catabolism. This pathway
      is involved in both mitochondria and peroxisome. While mitochondria breaks down
      fatty acids with short, medium and long carbon chains, peroxisomes are involved
      in the catabolism of very long and branched chain fatty acids, which are degraded
      by three enzymes: acyl-CoA oxidase, multifunctional enzyme and thiolase enzyme.
      The active pathway results mainly from a tight transcriptional control of these
      gene-encoding enzymes. Two major nuclear receptors that are highly expressed in
      this organ are involved in this control, e.g. PPARalpha (peroxisome proliferator
      activated receptor, alpha isoform) and HNF4alpha (hepatic nuclear factor 4, alpha
      isotype). Both are key regulators of liver lipid metabolism. While numerous
      papers have reported on the role of PPARalpha in liver lipid homeostasis, less is
      known on the implication of HNF4alpha in this metabolism. Moreover, very few
      studies have taken an interest in the important question of the implication of
      these two receptors and most particularly their crosstalk. This review therefore
      presents the current knowledge on the PPARalpha/HNF4alpha interplay in
      diversified DNA responsive elements and its relevance in the regulation fatty
      acid catabolism. It presents a review of the properties of the nuclear receptors
      PPARalpha and HNF4alpha, then the genes regulated by HNF4alpha and PPARalpha,
      particularly the peroxisomal enzyme target genes. To conclude, the consequences
      of the regulation of these genes in the liver by PPARalpha and HNF4alpha will be
      analyzed. The current data indicate the requirement of PPARalpha and HNF4alpha
      for regulation in the liver of peroxisomal and mitochondrial fatty acid beta
      oxidation, cholesterol and bile acid metabolism, lipoprotein metabolism and
      consequently the prevention of liver steatosis. However, several questions remain
      unsolved. To show the interplay of PPARalpha and HNF4alpha in the regulation of
      liver fatty acid metabolism, different strategies are proposed.

PMID- 22978399
TI  - Recent advances on stearoyl-Coa desaturase regulation in fatty liver diseases.
AB  - Stearoyl-CoA desaturase 1 (SCD-1) is a delta-9 fatty acid desaturase that
      catalyzes the synthesis of monounsaturated fatty acids. Indeed, SCD-1 is the
      critical control point regulating hepatic lipogenesis and lipid oxidation. Due to
      its central role in lipid metabolism in the liver, recent studies have focused on
      the involvement of SCD-1 in the development of fatty liver during obesity,
      diabetes mellitus, hypertension, excessive alcohol consumption, and in subjects
      with high triglyceride blood concentrations. The accumulation of fat in liver
      cells can be a sign that harmful conditions are developing, possibly associated
      with or leading to inflammation of the liver. This review evaluates the recent
      advances in our understanding of the regulation of SCD-1 expression and its role
      in the development of nonalcoholic and alcoholic hepatosteatosis. Animal models
      presenting a liver-specific loss or inhibition of SCD-1, as well as dietary
      interventions, have highlighted the important role of the enzyme in the
      accumulation of fat (fatty infiltration) in hepatocytes during both alcoholic and
      nonalcoholic liver diseases. The data summarized in this article support the
      notion that SCD-1 plays a direct role in the development of fatty liver diseases,
      and is not simply a marker of an unfavorable diet or hepatic disorder.
      Accordingly, SCD-1 represents a promising therapeutic target for the treatment of
      hepatic steatosis.

PMID- 22978400
TI  - Editorial: lipohepatotoxicity and nonalcoholic steatohepatitis (NASH)-like
      metabolic disorders.

PMID- 22978401
TI  - MC1R variants predisposing to concomitant primary cutaneous melanoma in a
      monozygotic twin pair.
AB  - BACKGROUND: Concomitant primary cutaneous melanoma in monozygotic twins has been
      reported in only two pairs but in neither of them genetic analysis was performed.
      Two high-penetrance susceptibility genes, CDKN2A and CDK4 and one low-penetrance
      gene, MC1R, are well-defined genetic risk factors for melanoma. MITF has been
      recently identified as a novel intermediate risk melanoma-predisposing gene. CASE
      PRESENTATION: We describe the extraordinary occurrence of a primary cutaneous
      invasive melanoma in two 44-year-old identical, female twins, on the same body
      site within 30 days of each other and report for the first time the genetic
      analysis of melanoma susceptibility genes in both twins. Data on characteristics
      of the twins were collected through a standardized questionnaire and skin
      examination. Exons 1alpha, 1beta, 2 and 3 of CDKN2A, exon 2 of CDK4, the entire
      open reading frame of MC1R and the recently described MITF c.952 G > A
      (p.Glu318Lys) variant were investigated by direct sequencing. Sequencing analysis
      of the high-penetrance susceptibility genes showed no changes in CDKN2A and in
      exon 2 of the CDK4 gene. Both patients were heterozygous for the same CDKN2A UTR
      c.*29C > G variant. Interestingly, the same two heterozygous variants of the MC1R
      were identified in both twins: the c.451C > T (p.Arg151Cys) and the c.456C > A
      (p.Tyr152*) variants. Neither patient showed the c.952 G > A (p.Glu318Lys)
      substitution in the MITF gene. CONCLUSIONS: Identification of two high-risk MC1R
      variants in our identical twins in the absence of CDKN2A and CDK4 mutations
      highlights the contribution of low penetrance genes, such as MC1R, in melanoma
      susceptibility.

PMID- 22978402
TI  - Sulforaphane prevention of diabetes-induced aortic damage was associated with the
      up-regulation of Nrf2 and its down-stream antioxidants.
AB  - BACKGROUND: Oxidative stress plays an important role in diabetes-induced
      vascular inflammation and pathogenesis. Nuclear factor E2-related factor-2 (Nrf2)
      is a transcription factor orchestrating antioxidant and cyto-protective responses
      to oxidative stress. In the present study, we tested whether sulforaphane (SFN)
      can protect the aorta from diabetes and, if so, whether the aortic protection is
      associated with up-regulation of Nrf2 and its down-stream antioxidants. METHODS:
      Type 1 diabetes was induced in FVB mice by multiple low-dose streptozotocin.
      Diabetic and age-matched control mice were treated with or without SFN at 0.5
      mg/kg daily in five days of each week for three months. At the end of 3 months
      treatment of SFN one set of mice were sacrificed to perform the experimental
      measurements. The second set of both diabetic and control mice were aged for
      additional 3 months without further SFN treatment and then sacrificed to perform
      the experimental measurements. Aortas from these mice were assessed for fibrosis,
      inflammation, oxidative damage, and Nrf2 expression and transcription by
      immunohistochemical staining and real-time PCR method, respectively. RESULTS:
      Diabetes induced significant increases in oxidative stress and inflammation in
      the aorta at both 3 and 6 months, and fibrotic response at 6 months. SFN
      completely prevented these diabetic pathogenic changes and also significantly up
      regulated the expression of Nrf2 and its down-stream antioxidants. CONCLUSIONS:
      These results suggest that diabetes-induced aortic fibrosis, inflammation, and
      oxidative damage can be prevented by SFN. The aortic protection from diabetes by
      SFN was associated with the up-regulation of Nrf2 and its downstream
      antioxidants.

PMID- 22978404
TI  - Cationic ruthenium catalysts for alkyne annulations with oximes by C-H/N-O
      functionalizations.
AB  - Cationic ruthenium(II) complexes enabled efficient redox-neutral annulations of
      alkynes with readily available oximes. The catalytic dehydrative C-H/N-O bond
      functionalization proved to be broadly applicable and was shown to proceed
      through a reversible cyclometalation.

PMID- 22978403
TI  - Restoration of dietary-fat induced blood-brain barrier dysfunction by anti
      inflammatory lipid-modulating agents.
AB  - BACKGROUND: Several studies have identified use of non-steroidal-anti
      inflammatory drugs and statins for prevention of dementia, but their efficacy in
      slowing progression is not well understood. Cerebrovascular disturbances are
      common pathological feature of Alzheimer's disease. We previously reported
      chronic ingestion of saturated fatty acids (SFA) compromises blood-brain barrier
      (BBB) integrity resulting in cerebral extravasation of plasma proteins and
      inflammation. However, the SFA-induced parenchymal accumulation of plasma
      proteins could be prevented by co-administration of some cholesterol lowering
      agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of
      this study was to explore lipid-lowering agents could reverse BBB disturbances
      induced by chronic ingestion of SFA's. METHODS: Wild-type mice were fed an SFA
      diet for 12 weeks to induce BBB dysfunction, and then randomised to receive
      atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for
      2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG) and amyloid-beta
      enriched apolipoprotein (apo)-B lipoproteins within brain parenchyme were
      quantified utilising immunofluorescence microscopy. RESULTS: Atorvastatin
      treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial
      reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a
      water-soluble statin was less effective than atorvastatin (lipid-soluble). Statin
      effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a
      lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG
      and apo B as effectively as atorvastatin. Our findings are consistent with the
      drug effects being independent of plasma lipid homeostasis. CONCLUSION: Our
      findings suggest that BBB dysfunction induced by chronic ingestion of SFA is
      reversible with timely introduction and sustained treatment with agents that
      suppress inflammation.

PMID- 22978405
TI  - Evaluation of a multi-herb supplement for erectile dysfunction: a randomized
      double-blind, placebo-controlled study.
AB  - BACKGROUND: Evidence is lacking for multi-ingredient herbal supplements claiming
      therapeutic effect in sexual dysfunction in men. We examined the safety and
      efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving
      male sexual function, in a double blind, randomized placebo-controlled, parallel
      groups, multi-centre study. METHODS: 78 men aged 25-50 years of age; suffering
      from mild to moderate erectile dysfunction (ED), participated in this study.
      Subjects were randomized to receive VXP or placebo at a dose of two capsules
      twice daily for 12 weeks. The international index of erectile function (IIEF) was
      the primary outcome measure of efficacy. Other efficacy measures were: Erectile
      Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone,
      Semen analysis, Investigator's Global assessment and Subjects' opinion. RESULTS:
      In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved
      significantly as compared to placebo. After 12 weeks of treatment, the mean (sd)
      IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP
      group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001).
      Similar results were observed in each of the remaining four domains of the IIEF
      (orgasmic function, sexual desire, intercourse satisfaction, and overall
      satisfaction).There was a significant difference for VXP versus placebo
      comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53)
      and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%)
      subjects from the VXP group and one (3%) from the placebo group wished to
      continue with the treatment they received. Investigator's global assessment rated
      VXP therapy as very good to excellent in more than 50% patients and placebo
      therapy as fair to good in about 25% of patients. Incidence of side effects and
      subject's rating for tolerability of treatment was similar in both groups.
      CONCLUSIONS: VigRX Plus was well tolerated and more effective than placebo in
      improving sexual function in men. TRIAL REGISTRATION: Clinical Trial Registry
      India, CTRI/2009/091/000099, 31-03-2009.

PMID- 22978406
TI  - How not to miss autoinflammatory diseases masquerading as urticaria.
AB  - Urticarial skin reactions are one of the most frequent problems seen by
      allergists and clinical immunologists in daily practice. The most common reason
      for recurrent wheals is spontaneous urticaria. There are, however, several less
      common diseases that present with urticarial rash, such as urticarial vasculitis
      and autoinflammatory disorders. The latter include cryopyrin-associated periodic
      syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated
      by increased interleukin-1 secretion. Apart from the urticarial rash, patients
      are suffering from a variety of systemic symptoms including recurrent fever
      attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often
      associated with a diagnostic delay of many years and do not respond to
      antihistamines and other treatments of urticaria. Also, the chronic inflammation
      may lead to long-term complications such as amyloidosis. It is therefore
      important not to miss these diseases when diagnosing and treating patients with
      chronic recurrent urticarial rash. Here, we present clinical clues and tips that
      can help to identify autoinflammatory disorders in patients presenting with
      chronic urticarial rash and discuss their clinical picture and management.

PMID- 22978407
TI  - When autologous chromatin becomes a foe.
AB  - Apoptotic cells are recognized and cleared by the innate immune system. This
      process severely influences the outcome of several important functions of the
      latter. Apoptotic cells serve as sources for autoantigens employed by immature
      dendritic cells to maintain tolerance, excellent to prevent autoimmune diseases
      disastrous when this causes tumor tolerance. Apoptotic cells orchestrate healing
      and repopulation of the tissues, in which they died, again advantageous during
      wound healing and in the resolution phase of infections but a disaster after
      tumor reducing therapies. Many highly pathogenic microorganisms and viruses mimic
      changes of apoptotic cells like exposure of phosphatidyl serine and abuse their
      immune silencing signals to escape immune detection and eradication. If
      autologous chromatin is not properly cleared it is misinterpreted by the immune
      system as virus and causes the secretion by phagocytes of type-1 interferons. The
      continuous presence of these cytokines challenges tolerance and leads to SLE-like
      autoimmunity.

PMID- 22978408
TI  - The use of a subanesthetic infusion of intravenous ketamine to allow withdrawal
      of medically prescribed opioids in people with chronic pain, opioid tolerance and
      hyperalgesia: outcome at 6 months.

PMID- 22978409
TI  - Recovery of functional oocytes from cultured premeiotic germ cells after kidney
      capsule transplantation.
AB  - The efficiency of in vitro culture systems for a premeiotic female germ cell is
      still low, mostly because of our incomplete understanding of the mechanisms
      controlling oogenesis and the obvious difficulties in reproducing the complex in
      vivo environment of such a process under in vitro conditions. Here we explored
      the possibility of recovering the developmental potential of mouse oocytes
      generated in vitro from premeiotic germ cells by transplantation under a kidney
      capsule of adult animals. To this aim, mouse embryonic ovaries of 12.5 days
      postcoitum cultured in vitro in a serum-free medium for 7 or 14 days, were
      transplanted beneath the kidney capsule of immunodeficient mice and analyzed
      after 21 (7+21 group) or 14 days (14+14 group). Cultured ovaries before
      transplantation showed delayed oocyte meiotic progression and follicle
      development. Interestingly, grafted ovaries of both groups, especially those of
      the 7+21 group, seemed able to restore the reproductive cycle of recipients.
      While the almost complete absence of primordial follicles was observed in grafted
      ovaries, oocytes from these ovaries showed transcript levels of genes associated
      to oocyte maturation similar to control. Moreover, the developmental stage of
      follicles and oocytes of the 7+21 group ovaries were comparable to that of 21
      days post partum in vivo ovaries, whereas significant developmental delay were
      found in the 14+14 group ovaries. Nevertheless, oocytes retrieved from
      transplanted ovaries of both groups matured (around 80%) and were fertilized in
      vitro (around 20%-45%). Two-cell embryos from the fertilized oocytes developed to
      hatching blastocysts (about 50%) or gave rise to healthy live offspring (from 6%
      to 10%) when transplanted in a host mother. In conclusion, our results indicate
      that premeiotic female germ cells cultured in vitro up to primordial/primary
      follicle stages preserve their capability to complete oogenesis and can be
      fertilized and generate live pups after transplantation into a suitable in vivo
      environment.

PMID- 22978411
TI  - Electronic publication of new animal names - an interview with Frank-T. Krell,
      commissioner of the International Commission on Zoological Nomenclature and chair
      of the ICZN ZooBank Committee.
AB  - On the 4th September 2012 the International Commission on Zoological Nomenclature
      announced an amendment to the International Code of Zoological Nomenclature
      allowing for electronic publication of the scientific names of animals. In this
      interview Frank-T. Krell discusses the implications of this amendment for authors
      wishing to publish descriptions of newly identified animal species in online and
      open access journals, and for the future of taxonomic science.

PMID- 22978410
TI  - Dynamic changes in genomic histone association and modification during activation
      of the ASNS and ATF3 genes by amino acid limitation.
AB  - Amino acid deprivation of mammalian cells triggers several signalling pathways,
      the AAR (amino acid response), that results in transcriptional activation. For
      the ASNS (asparagine synthetase) and ATF3 (activating transcription factor 3)
      genes, increased transcription occurs in conjunction with recruitment of ATF4 to
      the gene. In HepG2 cells, analysis of the ASNS and ATF3 genes during AAR
      activation revealed increases in histone H3K4me3 (histone 3 trimethylated Lys4)
      and H4Ac (acetylated histone 4) levels, marks associated with active
      transcription, but a concurrent loss of total H3 protein near the promoter. The
      dynamic nature of AAR-regulated transcription was illustrated by a decline in
      ASNS transcription activity within minutes after removal of the AAR stress and a
      return to basal levels by 2 h. Reversal of ASNS transcription occurred in
      parallel with decreased promoter-associated H4Ac and ATF4 binding. However, the
      reduction in histone H3 and increase in H3K4me3 were not reversed. In yeast,
      persistence of H3K4me3 has been proposed to be a 'memory' mark of gene activity
      that alters the responsiveness of the gene, but the time course and magnitude of
      ASNS induction was unaffected when cells were challenged with a second round of
      AAR activation. The results of the present study document changes in gene
      associated nucleosome abundance and histone modifications in response to amino
      acid-dependent transcription.

PMID- 22978412
TI  - Pain status and sedation level in Chinese children after cardiac surgery: an
      observational study.
AB  - AIMS AND OBJECTIVES: This study explored current pain status, sedation level and
      their trajectories in Chinese children after cardiac surgery. Background.  Pain
      and sedation management are fundamental care practices in the critical care
      setting, yet they both are frequently under-implemented for children after major
      surgery. DESIGN: Repeated observational design. METHODS: This study was conducted
      in a paediatric medical centre in Shanghai, China where 170 children who
      underwent cardiac surgery were recruited. Pain was measured with the face, legs,
      activity, cry, consolability scale and sedation levels with the COMFORT Behaviour
      Scale at 18 fixed time-points for three consecutive postoperative days. Results. 
      The study indicated that 95 children (55.9%) received continuous opioids for pain
      relief, and 61 children (35.9%) received no analgesics. Multiple sedatives were
      used for these children, including bolus phenobarbital for 117 children (68.8%),
      phenergan for 81 children (47.6%) and midazolam for three children (1.8%). The
      mean pain scores significantly decreased throughout the operation day (POD-0) to
      the 2nd postoperative day (POD-2) with the lowest score on POD-2. Less than 5% of
      pain assessments were identified as moderate to severe across all 2815
      observations. The sedation scores significantly increased through POD-0 to POD-2
      with the highest score on POD-2. The rate of over-sedation was 50.3% with <1%
      under-sedation occurring among all the observations. Results also suggested that
      the length of stay in the cardiac intensive care unit was a predictor of
      increased analgesic usage in the critical care setting (odds ratio: 1.72).
      CONCLUSIONS: Usage of analgesic and sedative agents in cardiac intensive care
      unit was variable and children experienced low pain scores but a high rate of
      over-sedation, indicating that healthcare providers should address ways to
      improve postoperative pain and sedation management in this population. RELEVANCE
      TO CLINICAL PRACTICE: The pain and sedation status for children after cardiac
      surgery changed across the postoperative days. Healthcare providers should be
      trained in the use of reliable tools to accurately monitor children's pain and
      sedation levels.

PMID- 22978413
TI  - Inhibition by curcumin of multiple sites of the transforming growth factor-beta1
      signalling pathway ameliorates the progression of liver fibrosis induced by
      carbon tetrachloride in rats.
AB  - BACKGROUND: At present there is no effective and accepted therapy for hepatic
      fibrosis. Transforming growth factor (TGF)-beta1 signaling pathway contributes
      greatly to hepatic fibrosis. Reducing TGF-beta synthesis or inhibiting components
      of its complex signaling pathway represent important therapeutic targets. The aim
      of the study was to investigate the effect of curcumin on liver fibrosis and
      whether curcumin attenuates the TGF-beta1 signaling pathway. METHODS: Sprague
      Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six
      weeks together with or without curcumin, and hepatic histopathology and collagen
      content were employed to quantify liver necro-inflammation and fibrosis.
      Moreover, the mRNA and protein expression levels of TGF-beta1, Smad2,
      phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF)
      were determined by quantitative real time-PCR, Western blot, or
      immunohistochemistry. RESULTS: Rats treated with curcumin improved liver necro
      inflammation, and reduced liver fibrosis in association with decreased alpha
      smooth muscle actin expression, and decreased collagen deposition. Furthermore,
      curcumin significantly attenuated expressions of TGFbeta1, Smad2, phosphorylated
      Smad2, Smad3, and CTGF and induced expression of the Smad7. CONCLUSIONS: Curcumin
      significantly attenuated the severity of CCl4-induced liver inflammation and
      fibrosis through inhibition of TGF-beta1/Smad signalling pathway and CTGF
      expression. These data suggest that curcumin might be an effective antifibrotic
      drug in the prevention of liver disease progression.

PMID- 22978414
TI  - PNPLA 3 I148M genetic variant associates with insulin resistance and baseline
      viral load in HCV genotype 2 but not in genotype 3 infection.
AB  - BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk
      factor associated with a higher frequency of fibrosis and cirrhosis. A single
      genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic
      steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected
      individuals have reported an association between this variant and prevalence of
      steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M
      variant on metabolic traits and treatment response in HCV genotype 2 and 3
      infected patients. METHODS: Three hundred and eighty-two treatment naive HCV
      genotype 2 or 3 infected patients were included in a phase III, open label,
      randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in
      which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was
      performed in a total of 359 Caucasian patients. RESULTS: In HCV genotype 2
      infected patients carrying the PNPLA3 148M allele, there was significantly
      increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at
      baseline as well as the first seven days of antiviral treatment. These results
      were not observed in HCV genotype 3 infected patients. CONCLUSIONS: Our results
      suggest a possible association between the PNPLA3 148M allele and insulin
      resistance as well as baseline viral load in HCV genotype 2, but not in genotype
      3.

PMID- 22978415
TI  - Conformational adaptation drives potent, selective and durable inhibition of the
      human protein methyltransferase DOT1L.
AB  - DOT1L is the human protein methyltransferase responsible for catalyzing the
      methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L,
      associated with the chromosomal translocation that is a universal hallmark of MLL
      rearranged leukemia, is a required driver of leukemogenesis in this malignancy.
      Here, we present studies on the structure-activity relationship of
      aminonucleoside-based DOT1L inhibitors. Within this series, we find that
      improvements in target enzyme affinity and selectivity are driven entirely by
      diminution of the dissociation rate constant for the enzyme-inhibitor complex,
      leading to long residence times for the binary complex. The biochemical K(i)  and
      residence times measured for these inhibitors correlate well with their effects
      on intracellular H3K79 methylation and MLL-rearranged leukemic cell killing.
      Crystallographic studies reveal a conformational adaptation mechanism associated
      with high-affinity inhibitor binding and prolonged residence time; these studies
      also suggest that conformational adaptation likewise plays a critical role in
      natural ligand interactions with the enzyme, hence, facilitating enzyme turnover.
      These results provide critical insights into the role of conformational
      adaptation in the enzymatic mechanism of catalysis and in pharmacologic
      intervention for DOT1L and other members of this enzyme class.

PMID- 22978416
TI  - Water-gas shift reaction on metal nanoclusters encapsulated in mesoporous ceria
      studied with ambient-pressure X-ray photoelectron spectroscopy.
AB  - Metal nanoclusters (Au, Pt, Pd, Cu) encapsulated in channels of mesoporous ceria
      (mp-CeO(2)) were synthesized. The activation energies of water-gas shift (WGS)
      reaction performed at oxide-metal interfaces of metal nanoclusters encapsulated
      in mp-CeO(2) (M@mp-CeO(2)) are lower than those of metal nanoclusters impregnated
      on ceria nanorods (M/rod-CeO(2)). In situ studies using ambient-pressure XPS (AP
      XPS) suggested that the surface chemistry of the internal concave surface of
      CeO(2) pores of M@mp-CeO(2) is different from that of external surfaces of CeO(2)
      of M/rod-CeO(2) under reaction conditions. AP-XPS identified the metallic state
      of the metal nanoclusters of these WGS catalysts (M@mp-CeO(2) and M/rod-CeO(2))
      under a WGS reaction condition. The lower activation energy of M@mp-CeO(2) in
      contrast to M/rod-CeO(2) is related to the different surface chemistry of the two
      types of CeO(2) under the same reaction condition.

PMID- 22978417
TI  - Prediction of macroscopic findings of hepatocellular carcinoma on hepatobiliary
      phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced
      magnetic resonance imaging: Correlation with pathology.
AB  - AIM: We aimed to correlate the macroscopic and magnetic resonance imaging (MRI)
      findings of hepatocellular carcinomas (HCC). METHODS: This was a multicenter
      study, whose study protocol was approved by each institutional review board. One
      hundred and forty-six resected nodules in 124 patients who had received a
      preoperative hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine
      pentaacetic acid-enhanced MRI (EOB-MRI) were analyzed. In both findings, we
      compared the diameter of HCC and macroscopic types divided into five types: (i)
      small nodular type with indistinct margin (SN-IM); (ii) simple nodular type (with
      distinct margin) (SN-DM); (iii) simple nodular type with extranodular growth (SN
      EG); (iv) confluent multinodular type (CMN); and (v) infiltrative type (IF).
      RESULTS: The diameters in each finding (Dsurg and DMRI ) were significantly
      correlated (R = 0.961), although Dsurg was larger than DMRI (P = 0.0216). There
      were significant differences between Dsurg in SN-IM and the other groups (P <
      0.0001). Sensitivity, specificity and accuracy were 5.3, 99.2 and 87; 84.8, 62.7
      and 81.4; 58.1, 91.3 and 84.2; 70.6, 91.5 and 89, in SN-IM, SN-DM, SN-EG and CMN,
      respectively. The kappa value of every size was as follows: all sizes, 0.45; 20
      mm or less, 0.23; more than 20 mm, 0.56. CONCLUSION: EOB-MRI could predict the
      macroscopic pathological findings except for SN-IM. Small tumor size might be
      helpful to diagnose SN-IM.

PMID- 22978418
TI  - Atopic and non-atopic eosinophilic oesophagitis are distinguished by
      immunoglobulin E-bearing intraepithelial mast cells.
AB  - AIMS: Eosinophilic oesophagitis (EoE) occurs in atopic individuals and features
      eosinophils and mast cells, but differences in the inflammatory cell density
      between the epithelium and lamina propria (LP) are not fully understood. The aim
      of this study was to determine if numbers of eosinophils, B lymphocytes and
      immunoglobulin E (IgE)-bearing mast cells are increased in the mucosa of EoE
      patients with and without concurrent atopy. METHODS AND RESULTS: Oesophageal
      biopsies containing >= 4 high-power fields (HPF) of epithelium and LP were
      identified for normal (n = 9), gastroesophageal reflux disease (GERD) (n = 5) and
      EoE (n = 25) patients. Patients were classified as atopic or not by clinical
      history. Immunohistochemistry identified mast cells, B lymphocytes and
      eosinophils. Eosinophil density was increased in the LP in EoE. Intraepithelial
      eosinophil density correlated with eosinophils/HPF, CD20(+) B lymphocyte density
      and tryptase(+) IgE(+) mast cell density. Increased intraepithelial IgE(+) cell
      density in EoE was associated with mast cells and not B lymphocytes.
      Intraepithelial IgE(+) mast cell densities were significantly higher in biopsies
      from the subgroup of EoE patients with atopy. CONCLUSIONS: EoE diagnosis using
      maximal eosinophil count/HPF correlates with average counts/mm(2), and
      intraepithelial eosinophil densities are higher in children than adults with EoE.
      In EoE, numbers of eosinophils and mast cells are increased in the LP. IgE
      bearing mast cells are increased in atopic EoE patients but not in non-atopic EoE
      patients.

PMID- 22978419
TI  - Effects of 60 minutes of hyperoxia followed by normoxia before coronary artery
      bypass grafting on the inflammatory response profile and myocardial injury.
AB  - BACKGROUND: Ischemic preconditioning induces tolerance against ischemia
      reperfusion injury prior a sustained ischemic insult. In experimental studies,
      exposure to hyperoxia for a limited time before ischemia induces a low-grade
      systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of
      the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced
      myocardial protection described by decreased release of cTn T in the 1st
      postoperative morning and reduces the release of inflammatory cytokines. METHODS:
      Forty patients with stable coronary artery disease underwent coronary artery
      bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96%
      oxygen for 60 minutes followed by by 33 (18-59) min normoxia before cardioplegia.
      RESULTS: In the 1st postoperative morning concentrations of cTnT did not differ
      between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in
      hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6
      (0.73 in controls and 1.47 in hyperoxia, p = 0.03) and IL-10/TNF-alpha (2.91 and
      8.81, resp., p = 0.015) were significantly drifted towards anti-inflammatory,
      whereas interleukins 6, 8and TNF-alpha and interferon-gamma showed marked
      postoperative rise, but no intergroup differences were found. CONCLUSIONS: Pre
      treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T
      in patients undergoing coronary artery bypass surgery. In the hyperoxia group
      higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL
      10/TNF-alpha towards anti-inflammatory.

PMID- 22978420
TI  - Relationship of serum osteocalcin levels with blood glucose, insulin resistance
      and lipid profile in central Indian men with type 2 diabetes.
AB  - OBJECTIVE: To assess the relationship of serum osteocalcin levels with blood
      glucose, insulin resistance and lipid profile in central Indian men with type 2
      diabetes. METHODS: Anthropometric and biochemical parameters were measured in 56
      newly diagnosed type 2 diabetic men and in 56 age and body mass index (BMI)
      matched controls. Insulin resistance was calculated by homeostasis model
      assessment of insulin resistance (HOMA-IR). RESULTS: After adjustment for age and
      BMI, osteocalcin levels were negatively correlated with fasting plasma glucose (p
      = 0.0004), fasting insulin (p = 0.0311), HOMA-IR (p = 0.0023), and triglycerides
      (p = 0.0095), and positively correlated with high density lipoprotein (HDL)
      cholesterol (p = 0.0042) in type 2 diabetic patients. In multivariate logistic
      regression analyses that adjusted for age, BMI, waist circumference and waist-to
      hip ratio, osteocalcin was inversely associated with the presence of type 2
      diabetes (p < 0.0001). CONCLUSION: Osteocalcin may play a protective role in the
      pathogenesis of type 2 diabetes, not only through direct involvement in glucose
      homeostasis, but also through improving lipid profile.

PMID- 22978422
TI  - Molecular dynamics simulations and structural descriptors of radioisotope glass
      vectors for in situ radiotherapy.
AB  - The low solubility (high durability) of yttrium aluminosilicate (YAS) glass is
      one of its most important properties for use in in situ radiotherapy. Simple
      parameters, such as silica or yttria content or network connectivity, are not
      sufficient to rationalize the dependence of the solubility on the glass
      composition observed experimentally. We performed classical molecular dynamics
      (MD) simulations of eight different YAS glasses of known solubility and analyzed
      the MD trajectories to identify specific structural features that are correlated
      and can be used to predict the solubility. We show that the (Si-)O-Si
      coordination number CN(SiOSi), the yttrium-yttrium clustering ratio R(YY), and
      the number of intratetrahedral O-Si-O bonds per yttrium atom N(intra) can be
      combined into a single structural descriptor s = f(CN(SiOSi),R(YY),N(intra)) with
      a high correlation with the solubility. The parameter s can thus be calculated
      from MD simulations and used to predict the solubility of YAS compositions,
      allowing one to adjust them to the range required by radiotherapy applications.
      For instance, its trend shows that high-silica- and low-yttria-content YAS
      glasses should be sufficiently durable for the radiotherapy application, although
      additional clinical considerations may set a lower limit to the yttria content.

PMID- 22978423
TI  - Multifunctional properties of soy milk fermented by Enterococcus faecium strains
      isolated from raw soy milk.
AB  - Lactic acid bacteria (LAB) isolated from soy milk were used to produce a
      multifunctional fermented food. Seven isolates were screened for their ability to
      produce peptides and free isoflavones in soy milk. The antihypertensive,
      antioxidant, and anti-inflammatory properties of the resulting fermented soy
      milks were evaluated in vitro using biochemical assays. Isolates 1-5 were found
      to be producers of fermented soy milk with angiotensin I converting enzyme
      inhibitory activity (ACEI). Isolate 3 was found to be a producer of free
      isoflavones that increased the antioxidant and anti-inflammatory potential of
      fermented soy milk. LAB isolates 2-5 were submitted to genetic profiling and a
      characterization scheme. These isolates were identified as  Enterococcus faecium
      , and none of them contained virulence determinants or resistance to antibiotics.
      In conclusion, this study shows that the application of E. faecium isolate 3 for
      multifunctional food production from soy milk could be a promising strategy in
      the prevention therapy against cardiovascular disease.

PMID- 22978424
TI  - Modification of fatty acid, essential oil and phenolic contents of salt-treated
      sweet marjoram (Origanum majorana L.) according to developmental stage.
AB  - Variation in the composition of Origanum majorana L. essential oil (EO) and fatty
      acids were studied under salt treatment. Plant material has been harvested at 2
      phenological stages: early vegetative stage (EVS) and late vegetative stage (LVS)
      or prefloral. Our results showed that the application of 75 mM NaCl increased
      total lipid contents in marjoram shoots and caused great qualitative changes in
      the fatty acids profiles. NaCl treatment reduced and stimulated the EO yields,
      respectively, at EVS and LVS and induced quantitative changes in the chemical EO
      composition in shoots. Phenolic contents were higher during the LVS than EVS in
      the absence and the presence of salt. Under control conditions, RP-HPLC analysis
      of the methanolic extract of marjoram dried shoots showed a predominance of
      flavonoid during the EVS whereas phenolic acids predominated during the LVS.
      However, under 75 mM NaCl, we noted a predominance of flavonoid at LVS and
      constant levels of phenolic and flavonoid classes at the EVS. For control
      treatment and at both EVS and LVS, the main components identified were
      respectively rosmarinic acid gallic as phenolic acids and amentoflavone as
      flavonoid. In the presence of salt and at the EVS, we observed a significant
      increase in trans-2 hydrocinnamic, gallic acid and quercetin-3-galactoside
      contents. However, for the LVS, salt induced a stimulation of gallic acid,
      apigenin, and amentoflavone. Our results showed that LVS had the highest contents
      of bioactive compounds, and could be considered as the best stage for harvesting
      marjoram plants. Practical Application:  In this study, the fatty acid
      composition, essential oil, and phenolic content of Origanum majorana were
      investigated. This is important for potential application of marjoram as
      functional food at the late vegetative stage. The richness of O. majorana in
      volatile and phenolic active compounds known for their antioxidant,
      antimicrobial, and insecticidal activities could support the utilization of this
      plant in a large field of application including cosmetic, pharmaceutical, agro
      alimentary, and biological defense.

PMID- 22978421
TI  - Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent
      and persistent sodium currents in large sensory neurons.
AB  - BACKGROUND: Gain-of-function mutations of the nociceptive voltage-gated sodium
      channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain
      disorder (PEPD). One characteristic of these mutations is slowed fast
      inactivation kinetics, which may give rise to resurgent sodium currents. It is
      long known that toxins from Anemonia sulcata, such as ATX-II, slow fast
      inactivation and skin contact for example during diving leads to various symptoms
      such as pain and itch. Here, we investigated if ATX-II induces resurgent currents
      in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate
      into human sensations. RESULTS: In large A-fiber related DRGs ATX-II (5 nM)
      enhances persistent and resurgent sodium currents, but failed to do so in small C
      fiber linked DRGs when investigated using the whole-cell patch-clamp technique.
      Resurgent currents are thought to depend on the presence of the sodium channel
      beta4-subunit. Using RT-qPCR experiments, we show that small DRGs express
      significantly less beta4 mRNA than large sensory neurons. With the beta4-C
      terminus peptide in the pipette solution, it was possible to evoke resurgent
      currents in small DRGs and in Nav1.7 or Nav1.6 expressing HEK293/N1E115 cells,
      which were enhanced by the presence of extracellular ATX-II. When injected into
      the skin of healthy volunteers, ATX-II induces painful and itch-like sensations
      which were abolished by mechanical nerve block. Increase in superficial blood
      flow of the skin, measured by Laser doppler imaging is limited to the injection
      site, so no axon reflex erythema as a correlate for C-fiber activation was
      detected. CONCLUSION: ATX-II enhances persistent and resurgent sodium currents in
      large diameter DRGs, whereas small DRGs depend on the addition of beta4-peptide
      to the pipette recording solution for ATX-II to affect resurgent currents.
      Mechanical A-fiber blockade abolishes all ATX-II effects in human skin (e.g.
      painful and itch-like paraesthesias), suggesting that it mediates its effects
      mainly via activation of A-fibers.

PMID- 22978425
TI  - Moonlighting osteoclasts as undertakers of apoptotic cells.
AB  - Rapid clearance of apoptotic cells, frequently referred to as efferocytosis, is
      crucial for the maintenance of tissue homeostasis and the prevention of
      autoimmunity. The common model of apoptotic cell clearance involves a system of
      released "Find me" and exposed "Eat me" signals on apoptotic cells, detected and
      recognized by matching receptors on macrophages or dendritic cells (DC), referred
      to as the phagocytic synapse. Osteoclasts share the monocyte lineage with these
      professional mononuclear phagocytes, thus raising the question if, in addition to
      bone resorption, osteoclasts can act as scavengers for apoptotic cells. Our qPCR
      data clearly show that osteoclasts express most of the genes required for dying
      cell clearance at mRNA levels similar to or even higher than those observed in M1
      macrophages, M2-macrophages or DC. Our microscopical analyses reveal that
      osteoclasts in fact can bind and/or engulf apoptotic cells in an essentially
      serum-independent fashion. Together with our data on the abundance of the
      respective mRNAs, these results identify the vitronectin receptor (integrin
      alpha(nu)beta(3))/milk fat globule-EGF factor 8 protein (MFG-E8) axis, the
      scavenger receptors (CD36, CD68 and class A macrophage scavenger receptor (SR
      A)), the complement/complement receptor axis, the Mer/Tyro3/Protein S axis, and
      the phosphatidylserine (PS) receptor brain-specific angiogenesis inhibitor 1
      (BAI1) as the most promising candidates to be involved in osteoclast-mediated
      efferocytosis.

PMID- 22978426
TI  - Synthesis, cytotoxic evaluation, docking and in silico pharmacokinetic prediction
      of 4-arylideneamino/cycloalkylidineamino 1, 2-naphthoquinone thiosemicarbazones.
AB  - In an attempt to develop potent anticancer agents, a series of 4
      arylideneamino/cycloalkylidineamino-1, 2-naphthoquinone thiosemicarbazones were
      synthesized and characterized using FT-IR, (1)H NMR, (13)C NMR spectroscopy and
      elemental analysis. The compounds were screened for antiproliferative activity
      against three human cancer cell lines (Hep-G2, MG-63 and MCF-7) using the MTT
      assay. Significant anticancer activity was observed for several members of the
      series. The compounds 4-(3, 4, 5-trimethoxybenzylidene amino) 1, 2-naphthoquinone
      2-thiosemicarbazone (TS10) and 4-(4-hydroxy-3-methoxy benzylideneamino) 1, 2
      naphthoquinone-2-thiosemicarbazone (TS13) were active cytotoxic agents in all
      three cancer cell lines, with IC50 values in the range of 3.5-6.4 uM. Further
      evaluation of some of these potent cytotoxic compounds demonstrated their good
      safety profile in a normal cell line (MCF-12A). Docking experiments showed a good
      correlation between the predicted glide scores and the IC50 values of these
      compounds. In silico ADME studies revealed that these compounds can be used for
      second generation development. 

PMID- 22978427
TI  - Sociodemographic and meteorological correlates of sudden infant death in Taiwan.
AB  - BACKGROUND: This study was designed, using three national datasets including the
      Taiwan Death Registry, Taiwan Birth Registry, and National Meteorological
      Dataset, to examine the sociodemographic, geographic and meteorological
      correlates of sudden infant death syndrome (SIDS). METHODS: One thousand, six
      hundred and seventy-one cases of SIDS occurring between 1994 and 2003, and 8355
      matched controls were included in this nested case-control study. RESULTS: Over
      the study period, the annual rate of SIDS declined only slightly, with an average
      annual rate of 57.9/10(5) . Male infants (adjusted odds ratio [AOR], 1.19; 95%
      confidence interval [CI]: 1.06-1.33), preterm births (AOR, 1.69; 95%CI: 1.33
      2.13), low birthweight (AOR, 2.87; 95%CI: 2.30-3.59), and birth order >=3 (AOR,
      1.62; 95%CI: 1.37-1.92) were the demographic risk factors for SIDS. Additionally,
      paternal age <25 years (AOR, 1.37; 95%CI: 1.09-1.71), urbanization (AOR, 1.46;
      95%CI: 1.20-1.78), lower paternal education (elementary and less; AOR, 1.28;
      95%CI: 1.01-1.64), and parental age difference >10 years (AOR, 1.72; 95%CI: 1.24
      2.39) were also associated with increased risk of SIDS. It was also noted that
      daily average temperature ranging from 9.2 degrees C to 14.2 degrees C (AOR,
      2.10; 95%CI: 1.67-2.64) was associated with the most increased risk, while
      temperature >=26.4 degrees C (AOR 0.60, 0.61) was significantly associated with
      the most reduced risk. CONCLUSION: Sociodemographic, geographic and
      meteorological data can be used to identify families in greater need of early
      guidance and to promote various prevention measures to avoid the occurrence of
      SIDS.

PMID- 22978428
TI  - Alternative oxidase impacts the plant response to biotic stress by influencing
      the mitochondrial generation of reactive oxygen species.
AB  - Previously, we showed that inoculation of tobacco with Pseudomonas syringae
      incompatible pv. maculicola results in a rapid and persistent burst of superoxide
      (O(2) (-) ) from mitochondria, no change in amount of mitochondrial alternative
      oxidase (AOX) and induction of the hypersensitive response (HR). However,
      inoculation with incompatible pv. phaseolicola resulted in increased AOX, no O(2)
      (-)  burst and no HR. Here, we show that in transgenic plants unable to induce
      AOX in response to pv. phaseolicola, there is now a strong mitochondrial O(2) (-)
      burst, similar to that normally seen only with pv. maculicola. This interaction
      did not however result in a HR. This indicates that AOX amount is a key
      determinant of the mitochondrial O(2) (-)  burst but also that the burst itself
      is not sufficient to induce the HR. Surprisingly, the O(2) (-)  burst normally
      seen towards pv. maculicola is delayed in plants lacking AOX. This delay is
      associated with a delayed HR, suggesting that the burst does promote the HR. A
      O(2) (-)  burst can also be induced by the complex III inhibitor antimycin A
      (AA), but is again delayed in plants lacking AOX. The similar mitochondrial
      response induced by pv. maculicola and AA suggests that electron transport is a
      target during HR-inducing biotic interactions.

PMID- 22978430
TI  - Modification and optimization of the bis-picolylamide-based relay protection for
      carboxylic acids to be cleaved by unusual complexation with Cu2+ salts.
AB  - A simple modification of our recently published protection scheme for carboxylic
      acids as amides resulted in a new protecting group with significantly improved
      properties. It requires shorter reaction times for deprotection and allows us to
      replace Cu(OTf)(2) by CuCl(2), indicating at the same time the importance of the
      nature of the anion of the Cu(2+) source. Since the new scheme fulfills all
      criteria required for an ideal protection group it should find widespread
      application in synthetic organic chemistry.

PMID- 22978429
TI  - Epigenetics and the transition from acute to chronic pain.
AB  - OBJECTIVE: The objective of this study was to review the epigenetic modifications
      involved in the transition from acute to chronic pain and to identify potential
      targets for the development of novel, individualized pain therapeutics.
      BACKGROUND: Epigenetics is the study of heritable modifications in gene
      expression and phenotype that do not require a change in genetic sequence to
      manifest their effects. Environmental toxins, medications, diet, and
      psychological stresses can alter epigenetic processes such as DNA methylation,
      histone acetylation, and RNA interference. As epigenetic modifications
      potentially play an important role in inflammatory cytokine metabolism, steroid
      responsiveness, and opioid sensitivity, they are likely key factors in the
      development of chronic pain. Although our knowledge of the human genetic code and
      disease-associated polymorphisms has grown significantly in the past decade, we
      have not yet been able to elucidate the mechanisms that lead to the development
      of persistent pain after nerve injury or surgery. DESIGN: This is a focused
      literature review of epigenetic science and its relationship to chronic pain.
      RESULTS: Significant laboratory and clinical data support the notion that
      epigenetic modifications are affected by the environment and lead to differential
      gene expression. Similar to mechanisms involved in the development of cancer,
      neurodegenerative disease, and inflammatory disorders, the literature endorses an
      important potential role for epigenetics in chronic pain. CONCLUSIONS: Epigenetic
      analysis may identify mechanisms critical to the development of chronic pain
      after injury, and may provide new pathways and target mechanisms for future drug
      development and individualized medicine.

PMID- 22978432
TI  - The influences of patient's satisfaction with medical service delivery,
      assessment of medical service, and trust in health delivery system on patient's
      life satisfaction in China.
AB  - BACKGROUND: Patient's satisfaction with medical service delivery/assessment of
      medical service/trust in health delivery system may have significant influence on
      patient's life satisfaction in China's health delivery system/in various kinds of
      hospitals.The aim of this study was to test whether and to what extent patient's
      satisfaction with medical service delivery/patient's assessments of various major
      aspects of medical service/various major aspects of patient's trust in health
      delivery system influenced patient's life satisfaction in China's health delivery
      system/in various kinds of hospitals. METHODS: This study collaborated with
      National Bureau of Statistics of China to carry out a 2008 national urban
      resident household survey in 17 provinces, autonomous regions, and municipalities
      directly under the central government (N = 3,386), and specified ordered probit
      models were established to analyze dataset from this household survey. RESULTS:
      The key considerations in generating patient's life satisfaction involved
      patient's overall satisfaction with medical service delivery, assessment of
      doctor-patient communication, assessment of medical cost, assessment of medical
      treatment process, assessment of medical facility and hospital environment,
      assessment of waiting time for medical service, trust in prescription, trust in
      doctor, and trust in recommended medical examination. But the major
      considerations in generating patient's life satisfaction were different among low
      level public hospital, high level public hospital, and private hospital.
      CONCLUSION: The promotion of patient's overall satisfaction with medical service
      delivery, the improvement of doctor-patient communication, the reduction of
      medical cost, the improvement of medical treatment process, the promotion of
      medical facility and hospital environment, the reduction of waiting time for
      medical service, the promotion of patient's trust in prescription, the promotion
      of patient's trust in doctor, and the promotion of patient's trust in recommended
      medical examination could all help promote patient's life satisfaction. But their
      promotion effects were different among low level public hospital, high level
      public hospital, and private hospital.

PMID- 22978431
TI  - Reversal of ion-charge selectivity renders the pentameric ligand-gated ion
      channel GLIC insensitive to anaesthetics.
AB  - pLGICs (pentameric ligand-gated ion channels) are a family of structurally
      homologous cation and anion channels involved in neurotransmission. Cation
      selective members of the pLGIC family are typically inhibited by general
      anaesthetics, whereas anion-selective members are potentiated. GLIC is a
      prokaryotic cation pLGIC and can be inhibited by clinical concentrations of
      general anaesthetics. The introduction of three mutations, Y221A (Y-3'A), E222P
      (E-2'P) and N224R (N0'R), at the selectivity filter and one, A237T (A13'T), at
      the hydrophobic gate, converted GLIC into an anion channel. The mutated GLIC
      (GLIC4) became insensitive to the anaesthetics propofol and etomidate, as well as
      the channel blocker picrotoxin. MD (molecular dynamics) simulations revealed
      changes in the structure and dynamics of GLIC4 in comparison with GLIC,
      particularly in the tilting angles of the pore-lining helix [TM2 (transmembrane
      helix 2)] that consequently resulted in different pore radius and hydration
      profiles. Propofol binding to an intra-subunit site of GLIC shifted the tilting
      angles of TM2 towards closure at the hydrophobic gate region, consistent with
      propofol inhibition of GLIC. In contrast, the pore of GLIC4 was much more
      resilient to perturbation from propofol binding. The present study underscores
      the importance of pore dynamics and conformation to anaesthetic effects on
      channel functions.

PMID- 22978433
TI  - Trends in outcomes and hospitalization costs for traumatic brain injury in adult
      patients in the United States.
AB  - Several new therapeutic strategies have been introduced for the management of
      adult traumatic brain injury (TBI) over the last decade, such as the development
      of management pathways and specialized TBI units and improved treatment of
      cerebral perfusion. The purpose of this study is to compare TBI-related
      hospitalization outcomes in the United States between two time periods, 1993-1994
      and 2006-2007. We determined the rates of occurrence, in-hospital outcomes, and
      mean hospital charges for patients hospitalized with adult TBI in 1993-1994 using
      the nationally representative all-payer Nationwide Inpatient Survey (NIS)
      database, and compared these outcomes with homologous data from 2006-2007. The
      incidence of TBI admissions was reduced by 35% in 2006-2007 compared with 1993
      1994; (22/100,000 versus 34/100,000 population; p<0.0001). The mean length of
      hospitalization (mean+/-SD, in days) was significantly lower in 2006-2007 than in
      1993-1994 (2.5+/-2.4 days versus 2.7+/-2.6 days; p<0.0001). In-hospital mortality
      increased significantly in 2006-2007 compared with 1993-1994 (0.8% versus 0.4%,
      p<0.0001). Average hospitalization charges were significantly higher in 2006-2007
      compared with 19993-1994 ($21,460+/-$21,212 versus $5,142+/-$4,625; p<0.0001),
      even after adjusting for inflation. In both time periods, most hospitalized adult
      TBI patients were graded as mild (98.2% in 1993-1994 versus 98.0% in 2006-2007;
      p=0.20). There was a significant increase in average hospitalization charges and
      death rates in all TBI severity subgroups in 2006-2007 compared with 1993-1994.
      The decline in rate of hospitalization between the two time periods was
      predominantly related to the decline in the number of admissions of patients with
      mild TBI. Although the number of TBI admissions was reduced, a significant
      increase in average hospitalization charges and in-hospital mortality rate was
      observed in 2006-2007 compared with 1993-1994.

PMID- 22978434
TI  - Development of a tool to describe the role of the clinical nurse consultant in
      Australia.
AB  - AIMS AND OBJECTIVES: To develop a tool for defining and measuring the role
      characteristics and responsibilities of an advanced practice nursing role in
      Australia. BACKGROUND: Internationally, there is considerable confusion about the
      precise role responsibilities of advanced practice nursing positions. In
      Australia, the clinical nurse consultant is an advanced practice role with five
      nominated domains of practice. However, there are no tools for measuring the
      performance of clinical nurse consultants against the listed domains. DESIGN AND
      METHODS: Participants were 56 clinical nurse consultants at a tertiary public
      hospital. The existing literature, an online survey, and position descriptions
      were used to generate the a priori themes for the initial template. Semi
      structured interviews were conducted (in 2010) to test the template
      characteristics. The template underwent multiple iterations in its development.
      RESULTS: A 50-item tool was devised, which consisted of five domains with a ten
      point hierarchical scale within each domain. In preliminary testing, the revised
      template was found to provide greater clarity regarding roles and grades than the
      original position descriptions. CONCLUSIONS: Further testing and refinement of
      the modified rating scale is needed, but it offers the possibility of a new tool
      that can be used by health service managers to determine the grade of a clinical
      nurse consultant position and for evaluating role performance. RELEVANCE TO
      CLINICAL PRACTICE: This preliminary study suggests that the tool provides a
      useful means of measuring advanced nursing practice and responsibilities across
      different domains and levels of appointment. The tool may be able to be adapted
      for use with other advanced practice nursing roles both within Australia and
      internationally.

PMID- 22978435
TI  - Correlation between shunt series and scoliosis radiographs in children with
      myelomeningoceles.
AB  - OBJECT: Over 85% of patients with myelomeningoceles require placement of a
      ventriculoperitoneal shunt for hydrocephalus, and between 25% and 85% of these
      patients develop scoliosis. Although most patients undergo repeated shunt series
      radiography to evaluate for device malfunction, scoliosis radiographs are less
      consistently obtained. The authors sought to determine if a correlation exists
      between these 2 radiographic techniques for a given patient, as shunt series are
      obtained with the patient supine, whereas scoliosis radiographs are acquired with
      the patient standing upright. The authors also endeavored to study if shunt
      series radiographs can reliably detect significant scoliosis. METHODS: The
      authors retrospectively reviewed a single institution's series of 593 patients
      with myelomeningoceles and identified all patients in whom a shunt series and
      scoliosis radiographs were obtained within a 6-month period. They reviewed the
      medical records and radiographs of these patients for demographic and
      radiographic parameters. They then applied a linear regression model and
      determined shunt series curve cutoffs to detect scoliotic curves greater than 20
      degrees  and 50 degrees . RESULTS: Of the 593 patients identified, 116 did not
      have radiographs available for interpretation. Of the remaining 477 patients, 201
      had radiographic evidence of scoliosis (42%), and 66 had both a shunt series and
      a scoliosis radiographs acquired within a 6-month interval. In 4 patients, both
      end vertebrae of the scoliotic curve could not be visualized on a single
      radiograph. The mean age of the remaining cohort was 10.6 +/- 5.2 years and the
      mean curve magnitude was 58 degrees  +/- 37 degrees . Using identical end
      vertebrae, the mean shunt series curve magnitude was 49 degrees  +/- 35 degrees .
      The mean interval between both radiographs was 2.3 +/- 3.3 months. The regression
      model showed a strong linear association between shunt series and scoliosis
      series curves. A curve greater than 19 degrees  on shunt series radiographs would
      detect significant curves of greater than 20 degrees  on scoliosis series with
      91% sensitivity and 78% specificity. A shunt series curve greater than 37 degrees
      had 100% sensitivity and 93% specificity in identifying significant scoliotic
      curves greater than 50 degrees . CONCLUSIONS: Although shunt series radiographs
      may not precisely depict scoliotic curve magnitude because the impact of gravity
      is negated, they may be useful in helping to confirm clinical suspicion of
      scoliosis. The authors' results suggest a strong correlation between both types
      of radiographs.

PMID- 22978436
TI  - Computed tomography morphometric analysis for lateral mass screw placement in the
      pediatric subaxial cervical spine.
AB  - OBJECT: Lateral mass screws are routinely placed throughout the subaxial cervical
      spine in adults, but there are few clinical or radiographic studies regarding
      lateral mass fixation in children. The morphology of pediatric cervical lateral
      masses may be associated with greater difficulty in obtaining adequate purchase.
      The authors examined the lateral masses of the subaxial cervical spine in
      pediatric patients to define morphometric differences compared with adults,
      establish guidelines for lateral mass instrumentation in children, and define
      potential limitations of this technique in the pediatric age group. METHODS:
      Morphometric analysis was performed on CT of the lateral masses of C3-7 in 56
      boys and 14 girls. Measurements were obtained in the axial, coronal, and sagittal
      planes. RESULTS: For most levels and measurements, results in boys and girls did
      not differ significantly; the few values that were significantly different are
      not likely to be clinically significant. On the other hand, younger (< 8 years of
      age) and older children (>= 8 years of age) differed significantly at every level
      and measurement except for facet angularity. Sagittal diagonal, a measurement
      that closely estimates screw length, was found to increase at each successive
      caudal level from C-3 to C-7, similar to the adult population. A screw acceptance
      analysis found that all patients >= 4 years of age could accept at least a 3.5 *
      10 mm lateral mass screw. CONCLUSIONS: Lateral mass screw fixation is feasible in
      the pediatric cervical spine, particularly in children age 4 years old or older.
      Lateral mass screw fixation is feasible even at the C-7 level, where pedicle
      screw placement has been advised in lieu of lateral mass screws because of the
      small size and steep trajectory of the C-7 lateral mass. Nonetheless, all
      pediatric patients should undergo high-resolution, thin-slice CT preoperatively
      to assess suitability for lateral mass screw fixation.

PMID- 22978437
TI  - Editorial: Lateral mass screws.

PMID- 22978438
TI  - Chyloretroperitoneum following anterior spinal surgery.
AB  - Injury to the lymphatic channels is a rare and relatively unknown complication of
      anterior approaches to the lumbar spine and can cause fluid to build up in the
      retroperitoneal space, resulting in a lymphocele. If they enlarge sufficiently,
      these collections of chyle in the abdomen can cause pain and bowel ischemia, and
      can compress nearby organs. The authors report 4 cases in which anterior
      approaches to the lumbar spine were complicated by a postoperative
      retroperitoneal chylous fluid collection. They describe the anatomy of the
      lymphatic system and pathophysiology of this disease entity, review the sparse
      literature on this subject, and recommend a treatment algorithm. Maintaining a
      high index of suspicion for this clinical entity in patients who have recently
      undergone an anterior approach to the thoracic or lumbar spine is vital to avoid
      delays in diagnosis and treatment.

PMID- 22978439
TI  - Epidemiology of traumatic spinal fractures: experience from medical university
      affiliated hospitals in Chongqing, China, 2001-2010.
AB  - OBJECT: The main objective of this study was to analyze the epidemiological data
      obtained from patients with traumatic spinal fracture at 2 university-affiliated
      hospitals in Chongqing, China. METHODS: The authors retrospectively reviewed the
      hospital records of all patients who suffered traumatic spinal fracture and were
      treated at Xinqiao Hospital and Southwest Hospital (both affiliated with The
      Third Military Medical University) between January 2001 and December 2010. The
      demographic characteristics, injury characteristics, and clinical outcomes of
      patients over this 10-year period were compared. RESULTS: A total of 3142
      patients (mean age 45.7 years, range 1-92 years) with traumatic spinal fractures
      were identified; 65.5% of the patients were male. The peak frequency of these
      injuries occurred in the 31- to 40-year-old age group. Accidental falls and
      traffic accidents were the most common causes of spinal fractures (58.9% and
      20.9%, respectively). Traffic accidents tended to occur in younger patients,
      whereas accidental falls tended to occur in older patients. The most common area
      of fracture was the thoracolumbar spine (54.9%). Cervical spinal fractures were
      significantly more common in patients injured in traffic accidents, while lumbar
      spinal fractures were more common in accidental fall patients. Using the American
      Spinal Injury Association (ASIA) classification, 479 (15.3%) patients were
      classified as having ASIA A injuries; 913 (29.1%), ASIA B, ASIA C, or ASIA D; and
      1750 (55.7%), ASIA E. ASIA A injuries were more common in patients who suffered
      thoracic spinal fractures (15.09%) than in those with fractures in other areas of
      the spine. A total of 954 (30.4%) patients had associated nonspinal injuries. Of
      these patients, 389 (40.78%) suffered a thoracic injury, and 191 (20.02%)
      sustained a head and neck injury. The length of hospitalization differed
      significantly between the accidental falls from high heights and falls from low
      heights, as did the mean cost of hospitalization (p < 0.05), but no significant
      difference was found between accidental falls from high heights and traffic
      accidents (p > 0.05). The length of hospitalization differed significantly among
      the 3 groups according to the ASIA classification, as did the mean cost of
      hospitalization (p < 0.05). Of patients with incomplete lesions, 39.3% improved 1
      or more grades in ASIA classification during hospitalization. CONCLUSIONS:
      Accidental falls emerged as the leading cause of traumatic spinal fracture in
      this study, and the numbers of fall-induced and sports-related injuries increased
      steadily with age. These results indicate that there should be increased concern
      for the consequences of fall- and sports-related injuries among the elderly.

PMID- 22978440
TI  - The effect of metformin and thiazolidinedione use on lung cancer in diabetics.
AB  - BACKGROUND: Metformin and the thiazolidinediones (TZDs) may have a protective
      effect against the development of lung cancer. METHODS: Patients with diabetes
      mellitus (DM) were identified from the electronic medical records of the
      Cleveland Clinic. Diabetics with lung cancer were identified then verified by
      direct review of their records. Control subjects were matched with cancer
      subjects 1:1 by date of birth, sex, and smoking history. The frequency and
      duration of diabetic medication use was compared between the groups. The cancer
      characteristics were compared between those with lung cancer who had and had not
      been using metformin and/or a TZD. RESULTS: 93,939 patients were identified as
      having DM. 522 lung cancers in 507 patients were confirmed. The matched control
      group was more likely to have used metformin and/or a TZD (61.0% vs. 41.2%, p <
      0.001 for any use; 55.5% vs. 24.6%, p < 0.001 for >24 months vs. 0-12 months). In
      the group with lung cancer, those who had used metformin alone had a different
      histology distribution than those who received neither metformin nor a TZD, were
      more likely to present with metastatic disease (40.8% vs. 28.2%, p = 0.013), and
      had a shorter survival from the time of diagnosis (HR 1.47, p < 0.005).
      CONCLUSIONS: The use of metformin and/or the TZDs is associated with a lower
      likelihood of developing lung cancer in diabetic patients. Diabetics who develop
      lung cancer while receiving metformin may have a more aggressive cancer
      phenotype.

PMID- 22978441
TI  - Biotin- and glycoprotein-coated microspheres: potential surrogates for studying
      filtration of cryptosporidium parvum in porous media.
AB  - Cryptosporidium parvum is a waterborne pathogen, yet no suitable surrogate has
      been established for quantifying its filtration removal in porous media. Carboxyl
      polystyrene microspheres with size, density, and shape similar to C. parvum were
      coated with biotin (free and containing amine, NH(2)) and glycoprotein. These
      biomolecules have isoelectric points similar to C. parvum (pH ~ 2), and
      glycoprotein is a major type of surface protein that oocysts possess. Zeta
      potential (zeta) and filtration removal of particles in sand of two different
      grain sizes were examined. Compared to unmodified microspheres, modified
      microspheres achieved a superior match to the oocysts in zeta, concentration,
      mass recovery, and collision coefficient. They showed the same log reduction in
      concentration as oocysts, whereas results from unmodified microspheres deviated
      by 1 order of magnitude. Of the three types of modified microspheres,
      glycoprotein-coated microspheres best resembled oocyst concentration, despite
      having zeta similar to NH(2)-biotin-coated microspheres, suggesting that surface
      protein also played an important role in particle attachment on solid surfaces.
      With further validation in environmental conditions, the surrogates developed
      here could be a cost-effective new tool for assessing oocyst filtration in porous
      media, for example, to evaluate the performance of sand filters in water and
      wastewater treatment, water recycling through riverbank filtration, and aquifer
      recharge.

PMID- 22978442
TI  - Fitness consequences of female multiple mating: a direct test of indirect
      benefits.
AB  - BACKGROUND: The observation that females mate multiply when males provide nothing
      but sperm - which sexual selection theory suggests is unlikely to be limiting -
      continues to puzzle evolutionary biologists. Here we test the hypothesis that
      multiple mating is prevalent under such circumstances because it enhances female
      fitness. We do this by allowing female Trinidadian guppies to mate with either a
      single male or with multiple males, and then tracking the consequences of these
      matings across two generations. RESULTS: Overall, multiply mated females produced
      67% more F2 grand-offspring than singly mated females. These offspring, however,
      did not grow or mature faster, nor were they larger at birth, than F2 grand
      offspring of singly mated females. Our results, however, show that multiple
      mating yields benefits to females in the form of an increase in the production of
      F1. The higher fecundity among multiply mated mothers was driven by greater
      production of sons but not daughters. However, contrary to expectation,
      individually, the offspring of multiply mated females do not grow at different
      rates than offspring of singly mated females, nor do any indirect fitness
      benefits or costs accrue to second-generation offspring. CONCLUSIONS: The study
      provides strong evidence that multiple mating is advantageous to females, even
      when males contribute only sperm. This benefit is achieved through an increase in
      fecundity in the first generation, rather than through other fitness correlates
      such as size at birth, growth rate, time to sexual maturation and survival.
      Considered alongside previous work that female guppies can choose to mate with
      multiple partners, our results provide compelling evidence that direct fitness
      benefits underpin these mating decisions.

PMID- 22978444
TI  - Tumor endothelial markers as a target in cancer.
AB  - INTRODUCTION: Several anti-angiogenic agents have been developed and some of them
      have been clinically applied in the tumor therapy. Anti-angiogenic therapy faces
      some hurdles: inherent or acquired resistance, increased invasiveness, and lack
      of biomarkers. Characterization of tumor endothelial markers may help to target
      endothelium and to identify potential predictive factors of response to anti
      angiogenic therapies. Numerous surrogates, angiogenic and endothelium markers
      have emerged from recent pre-clinical studies, including physiological and
      soluble molecules in plasma and from platelets, circulating cells, tumor tissue
      factors and imaging markers. However, no wholly validated biomarkers currently
      exist to predict the success or the failure of the anti-angiogenic therapy of
      cancer. Therefore, the research of suitable and validate biomarkers is currently
      ongoing. AREAS COVERED: This review provides an overview of the status of our
      knowledge concerning tumor endothelial markers, therapeutics targeting, possible
      resistance mechanisms and predictive value of these biomarkers and discuss future
      strategies to use and identify them in the anti-angiogenic therapy. EXPERT
      OPINION: Anti-angiogenesis is a milestone to improve the treatment of several
      types of cancer and predictive biomarkers for a response to anti-endothelium
      therapy are one of the most important challenges for anti-angiogenesis research.

PMID- 22978443
TI  - Flexible trial design in practice - stopping arms for lack-of-benefit and adding
      research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized
      controlled trial.
AB  - BACKGROUND: Systemic Therapy for Advanced or Metastatic Prostate cancer:
      Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that
      follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological
      and practical issues arising with (1) stopping recruitment to research arms
      following a pre-planned intermediate analysis and (2) adding a new research arm
      during the trial. METHODS: STAMPEDE recruits men who have locally advanced or
      metastatic prostate cancer who are starting standard long-term hormone therapy.
      Originally there were five research and one control arms, each undergoing a pilot
      stage (focus: safety, feasibility), three intermediate 'activity' stages (focus:
      failure-free survival), and a final 'efficacy' stage (focus: overall survival).
      Lack-of-sufficient-activity guidelines support the pairwise interim comparisons
      of each research arm against the control arm; these pre-defined activity cut-off
      becomes increasingly stringent over the stages. Accrual of further patients
      continues to the control arm and to those research arms showing activity and an
      acceptable safety profile. The design facilitates adding new research arms should
      sufficiently interesting agents emerge. These new arms are compared only to
      contemporaneously recruited control arm patients using the same intermediate
      guidelines in a time-delayed manner. The addition of new research arms is subject
      to adequate recruitment rates to support the overall trial aims. RESULTS: (1)
      Stopping Existing Therapy: After the second intermediate activity analysis,
      recruitment was discontinued to two research arms for lack-of-sufficient
      activity. Detailed preparations meant that changes were implemented swiftly at
      100 international centers and recruitment continued seamlessly into Activity
      Stage III with 3 remaining research arms and the control arm. Further regulatory
      and ethical approvals were not required because this was already included in the
      initial trial design.(2) Adding New Therapy: An application to add a new research
      arm was approved by the funder, (who also organized peer review), industrial
      partner and regulatory and ethical bodies. This was all done in advance of any
      decision to stop current therapies. CONCLUSIONS: The STAMPEDE experience shows
      that recruitment to a MAMS trial and mid-flow changes its design are achievable
      with good planning. This benefits patients and the scientific community as
      research treatments are evaluated in a more efficient and cost-effective manner.
      TRIAL REGISTRATION: ISRCTN78818544, NCT00268476. First patient into trial: 17
      October 2005. First patient into abiraterone comparison: 15 November 2011.

PMID- 22978445
TI  - Isolation and characterization of five glycerol esters from Wuhan propolis and
      their potential anti-inflammatory properties.
AB  - Five new glycerol esters including 2-acetyl-1-coumaroyl-3-cinnamoylglycerol (13),
      (+)-2-acetyl-1-feruloyl-3-cinnamoylglycerol (14), (-)-2-acetyl-1-feruloyl-3
      cinnamoylglycerol (15), 2-acetyl-1,3-dicinnamoylglycerol (16), and (-)-2-acetyl-1
      (E)-feruloyl-3-(3"(zeta),16")-dihydroxy-palmitoylglycerol (17) were isolated from
      methanolic extract of Wuhan propolis. The chemical structures of the five new
      compounds were confirmed by (1)H and (13)C NMR and HR-MS spectra. Twelve minor
      constituents in the Wuhan propolis extract were tentatively identified by UPLC-Q
      TOF-MS, according to their characteristic UV spectrum, retention times, and
      accurate MS data. The anti-inflammatory activities of the five new compounds were
      studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage cells.
      All five compounds exhibited remarkable inhibitory effects on interleukin (IL)
      1beta, IL-6, and cyclooxygenase (COX)-2 mRNA expressions at 10 and 100 MUM,
      suggesting that Wuhan propolis may serve as a potential anti-inflammatory
      functional food ingredient or nutraceutical. 

PMID- 22978446
TI  - 19F-NMR, 1H-NMR, and fluorescence studies of interaction between 5-fluorouracil
      and polyglycerol dendrimers.
AB  - Polyglycerol dendrimers (PGDs), which exhibit a well-defined structure consisting
      of only glycerol units, were examined as a host molecule of 5-fluorouracil (5-Fu)
      used as a model anticancer drug. (19)F- and (1)H-NMR titrations and fluorescence
      measurements were performed to estimate the molecular interaction between PGDs
      and 5-Fu in a buffer. Results of the NMR titrations revealed that PGD of
      generation 3 (PGD-G3) encapsulated 5-Fu in the buffer, whereas PGD-G2 and G1
      partially incorporated 5-Fu molecule into the space. Fluorescent spectra of 5-Fu
      in the presence of PGD-G3 indicated that the diketo (lactam) form of 5-Fu changed
      to the enol-keto (lactim) form of 5-Fu, suggesting attraction of the imine proton
      of 5-Fu by ether oxygen of PGD-G3. Therefore, the encapsulation state of 5-Fu in
      PGDs at molecular level was modulated by the well-defined branched structure
      depending on the generation of PGDs.

PMID- 22978447
TI  - Consumer input for developing human food products made with sorghum grain.
AB  - Because sorghum grain has important characteristics (for example, great
      antioxidant profile) for introduction into the regular human diet, producers and
      industry aim to develop successful products using sorghum as the base. The 1st
      step in developing products attractive for consumers is understanding consumer
      needs and expectations. Conjoint analysis determines attributes which may be
      important or unimportant for one product. In this study, focus groups and
      conjoint analysis were used to establish which attributes are helpful for
      promoting purchase intent of sorghum grain products. Once those characteristics
      were chosen, a national survey was conducted to confirm the selection. During the
      focus groups, the heath aspects of grain products seemed to be the most appealing
      for consumers, whereas conjoint analysis showed that sensory attributes were the
      principal drivers for purchase intent. PRACTICAL APPLICATION: The data presented
      in this study are essential for industry as a starting point for developing
      sorghum grain based food products. It is necessary to address consumers' demands
      to ensure new products' success in the market, and the present study clearly
      shows this consumers' input.

PMID- 22978448
TI  - Prevalence of chronic pain among Libyan adults in Derna City: a pilot study to
      assess the reliability, linguistic validity, and feasibility of using an Arabic
      version of the structured telephone interviews questionnaire on chronic pain.
AB  - There are few studies estimating the prevalence of chronic pain in countries from
      the Middle East. We translated the Structured Telephone Interviews Questionnaire
      on Chronic Pain from English into Arabic and assessed its reliability and
      linguistic validity before using it in a telephone survey in Libya to gather
      preliminary prevalence data for chronic pain. Intraclass correlations for scaled
      items were high, and there were no differences in answers to nominal items
      between the first and second completions of the questionnaire. One hundred and 4
      individuals participated in a telephone survey. The prevalence of chronic pain
      was 25.0% (95% CI, 16.7% to 33.3%) and 50.0% (95% CI: 30.8% to 69.2) of the
      participants with chronic pain scored >= 12 on the Arabic S-LANSS. Mean +/- SD
      duration of pain was 2.8 +/- 1.2 years, and pain was more frequent in women (P =
      0.02). 53.8% of participants had taken prescription medication for their pain,
      and 76.9% had used nondrug methods of treatment including traditional Libyan
      methods such as Kamara, a local herbal concoction. Eighty percent believed that
      their doctor would rather treat their illness than their pain, and 35% reported
      that their doctor did not think that their pain was a problem. Some participants
      complained that the questionnaire was too long with a mean +/- SD call duration
      of 20 +/- 5.4 minutes. We conclude that the Arabic Structured Telephone
      Interviews Questionnaire on Chronic Pain was reliable and linguistically valid
      and could be used in a large-scale telephone survey on the Libyan population. Our
      preliminary estimate of prevalence should be considered with caution because of
      the small sample size.

PMID- 22978449
TI  - Nm23-H1 nuclear expression is associated with a more favourable prognosis in
      laryngeal carcinoma: univariate and multivariate analysis.
AB  - AIMS: To use image analysis and multivariate analysis to investigate the
      prognostic significance of Nm23-H1 subcellular localization in a large cohort of
      laryngeal squamous cell carcinomas (LSCCs). METHODS AND RESULTS: Nm23-H1 total
      and nuclear levels were immunohistochemically determined and calculated with an
      image analysis system in 104 consecutively operated LSCCs. The mean follow-up was
      58.3 +/- 35.1 months (median 45 months). Total Nm23-H1 levels correlated only
      with patient stratification by pT (P=0.01). Mean nuclear Nm23-H1 levels were
      lower in patients with recurrent disease (P=0.01), and disease-free survival
      (DFS) was longer in patients whose nuclear levels of Nm23-H1 were >2.0% than in
      those with levels <= 2.0% (P=0.019). On multivariate analysis, Nm23-H1 nuclear
      expression [hazard ratio (HR) 2.59, P=0.005] and N stage (HR 3.60, P=0.0001) were
      prognostically significant in relation to DFS. CONCLUSIONS: In LSCC, Nm23-H1
      nuclear expression may be useful for identifying patients at higher risk of
      recurrence after treatment and who might be considered for more aggressive
      therapy. Further investigations are needed before Nm23-H1 can be considered for
      use in targeted treatments for LSCC.

PMID- 22978450
TI  - Colloidal nanocrystals embedded in macrocrystals: robustness, photostability, and
      color purity.
AB  - The incorporation of colloidal quantum dots (QDs) into ionic crystals of various
      salts (NaCl, KCl, KBr, etc.) is demonstrated. The resulting mixed crystals of
      various shapes and beautiful colors preserve the strong luminescence of the
      incorporated QDs. Moreover, the ionic salts appear to be very tight matrices,
      ensuring the protection of the QDs from the environment and as a result providing
      them with extraordinary high photo- and chemical stability. A prototype of a
      white light-emitting diode (WLED) with a color conversion layer consisting of
      this kind of mixed crystals is demonstrated. These materials may also find
      applications in nonlinear optics and as luminescence standards.

PMID- 22978451
TI  - Correlation between DAS-28 and neopterin as a biochemical marker of immune system
      activation in early rheumatoid arthritis.
AB  - OBJECTIVE: The objective of this study was to evaluate neopterin plasma
      concentrations in patients with early Rheumatoid Arthritis (RA) and correlate
      them with disease activity. METHODS: This is a 28-month prospective study carried
      out on 65 individuals. There were 27 patients with early RA and 38 healthy
      volunteers as control group. Enzyme immunoassay was used to measure
      concentrations of neopterin and anti-cyclic citrullinated peptide (CCP)
      antibodies. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured
      turbidimetrically, and antinuclear antibodies (ANA) were detected by
      immunofluorescence. Patients with early RA disease activity were divided into 4
      groups according to DAS-28 criteria. Neopterin concentrations in RA patients were
      compared to conventional RA diagnostic serological markers. RESULTS: Healthy
      volunteers had a mean neopterin concentration of 5.63 +/- 0.38 [1.36-9.93] nmol.
      L(- 1). A statistically significant elevation of neopterin mean concentration was
      found on early RA patients: mean value of 8.92 +/- 0.93 [3.94-28.3] nmol. L(- 1)
      (p < 0.001). Pearson product moment correlation suggests a correlation between
      neopterin concentrations and DAS-28 (r = 0.208, p = 0.065). The analysis of the
      mean values grouped according with the DAS-28 criteria showed a correspondence
      between these means, with a Pearson correlation coefficient r = 0.979, p = 0.021.
      CRP concentrations also showed a similar trend. Anti-CCP antibodies and RF
      revealed a positive relationship with RA activity. Such a correlation was not
      found with ANA results. CONCLUSIONS: The elevation of plasma neopterin
      concentrations in early RA patients may indicate stimulation of immune response.
      Good correlation between neopterin concentrations and DAS-28 may facilitate
      assessing disease activity.

PMID- 22978452
TI  - Assessment of circulatory adjustments during underwater apnoea in elite divers by
      means of a portable device.
AB  - AIM: Considering that sympathetic activation is induced by exercise, it is
      reasonable to assume that hemodynamic adjustments to exercise act in opposition
      to those elicited by the diving response. However, cardiovascular measurements
      have never been performed during underwater dynamic apnoea (DA), and this
      hypothesis remains speculative. METHODS: Data concerning heart rate (HR), stroke
      volume (SV) and cardiac output (CO) during static apnoea (SA) and DA were
      collected from 12 elite divers by means of an impedance cardiograph adapted to
      the underwater environment. Mean arterial pressure (MBP), systemic vascular
      resistance (SVR) and arterial oxygen saturation (SaO(2)) were also assessed. Five
      trials were performed by the divers: head-out immersion during normal breathing
      (test A); 3 min of SA immersed at the surface (B) and at 3 m depth (C); DA till
      exhaustion immersed at the surface (D) and at 3 m depth (E). RESULTS: Both B and
      C conditions led to bradycardia (-17%) compared to A and also induced a decrement
      in SV (-8%) and in CO (-25%), while MBP was maintained because of an increase in
      SVR. A significant MBP increment (+11%) was detected only during tests D and E,
      when a SaO(2) drop was also present, whereas HR, SV and CO remained unchanged.
      CONCLUSION: We concluded that typical diving response was present only during SA,
      while sympathetic activation was induced by exercise during DA, which partially
      obscured the effects of the diving response.

PMID- 22978453
TI  - Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour
      bearing mice.
AB  - BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has
      shown anti-tumour properties in vitro. This study attempts to confirm these
      effects in vivo and measure effects on the immune system. METHODS: Kunming mice
      transplanted with Sarcoma 180 cells were treated with ASMq (2-8 g/kg/day) by
      intra-gastric administration compared to model and cyclophosphamide (20
      mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and
      tumours were removed, weighed, and processed for histopathological analysis.
      Blood samples were also taken for haematological and biochemical analyses
      including TNF-alpha , IL-1 beta and IL-2. Splenic lymphocyte function was
      measured with MTT; lymphocyte subpopulations were measured by flow cytometry.
      RESULTS: ASMq treated animals had reduced tumour volume compared to model and
      increased concentrations of TNF-alpha, IL-1beta and IL-2 compared to untreated
      and to cyclophosphamide-treated animals. No histopathological alterations were
      observed. The absence of viable S180 cells and the presence of necrotic cells and
      granulation tissue were observed in tumour tissue of treated animals. The effect
      on T lymphocytes was unclear. CONCLUSIONS: ASMq confirmed in vivo anti-tumour
      effects observed in vitro, which may be at least in part mediated by increased
      immune activity.

PMID- 22978454
TI  - Cross-cultural adaptation of the CHO-KLAT for boys with hemophilia in rural and
      urban China.
AB  - BACKGROUND: Quality of life (QoL) is increasingly recognized as an important
      outcome measure in clinical trials. The Canadian Hemophilia Outcomes-Kids Life
      Assessment Tool (CHO-KLAT) shows promise for use in China. OBJECTIVE: To adapt
      the CHO-KLAT version 2.0 for use in clinical trials in China. METHODS: Forward
      and back translations of the CHO-KLAT2.0 were completed in 2008. Between October
      2009 and June 2010, a series of 3 focus groups were held with 20 boys and 31
      parents in rural and urban China to elicit additional concepts, important to
      their QoL, for the Chinese CHO-KLAT2.0. All of the items identified by boys and
      parents were reviewed by a group of experts, resulting in a Chinese version of
      the CHO-KLAT2.0. This version underwent a detailed cognitive debriefing process
      between October 2010 and June 2011. Thirteen patient-parent pairs participated in
      this cognitive debriefing process until a stable and clearly understood Chinese
      version of the CHO-KLAT2.0 was obtained. RESULTS: The initial back translation of
      the Chinese CHO-KLAT2.0 was slightly discrepant from the original English version
      on 12 items. These were all successfully adjudicated. The focus groups identified
      9 new items that formed an add-on Socio-Economic Context (SEC) module for China.
      Linguistic improvements were made after the 2nd, 5th, 7th and 13th cognitive
      debriefings pairs and affected a total of 18 items. The result was a 35 item CHO
      KLAT2.0 and a SEC module in Simplified Chinese, both of which have good content
      validity. CONCLUSION: This detailed process proved to be extremely valuable in
      ensuring the items were accurately interpreted by Chinese boys with hemophilia
      ages <=18 years. The need for the additional SEC module highlighted the different
      context that currently exists in China with regard to hemophilia care as compared
      to many Western countries, and will be important in tracking progress within both
      rural and urban China over time. Changes based on the cognitive debriefings
      suggest that expert verbatim translation alone is not sufficient. The Chinese
      version of the CHO-KLAT2.0 is well understood by boys with hemophilia in China.
      Next steps will be to test its construct validity and reliability in boys with
      hemophilia in China.

PMID- 22978455
TI  - Clues to apoptosis pathway involvement in hemolysis, elevated liver enzyme, and
      low platelet (HELLP) syndrome and intrauterine growth restriction (IUGR).
AB  - OBJECTIVE: The neurotrophin family comprises molecules involved in growth,
      differentiation, survival, regeneration, normal functions of the neuronal system,
      and in angiogenesis. We have investigated the expression pattern of neurotrophic
      signaling molecules in pregnancies complicated by elevated liver enzyme, and low
      platelet (HELLP) syndrome and intrauterine growth restriction (IUGR). METHODS:
      Placentas from normal and pathological pregnancies were collected. Macroarray
      analysis was performed and the data were confirmed by real-time PCR. RESULTS:
      Real-time PCR analyses (pathological vs. normal pregnancies) confirmed a
      significant down-regulation for IL-6, STAT3alpha, STAT3beta, and Bcl-2. The
      expression of Mcl-1 isoform 1 (long) was significantly increased. CONCLUSIONS: We
      suggest that decreased expression of IL-6 could mean that abnormalities in the
      immunological system function involve inflammatory cytokines other than IL-6 in
      examined pathological pregnancies. The STAT3alpha and STAT3beta down-regulation
      lead to a marked reduction of cellular transcriptional activity. Decreased
      expression of IL-6 is associated with a down-regulation of Bcl-2 but not of Mcl-1
      isoform 1, suggesting that these two antiapoptotic proteins may function
      independently and that Mcl-1 may have a distinct role in controlling apoptotic
      pathway.

PMID- 22978456
TI  - Stereoselective synthesis of enamides by Pd-catalyzed hydroamidation of electron
      deficient terminal alkynes.
AB  - Hydroamidation of electron-deficient terminal alkynes by amides in presence of Pd
      catalyst has been exploited for the stereoselective synthesis of Z-enamides. The
      possible intramolecular hydrogen bonding between the amido proton and carbonyl
      oxygen of ester group provides the extra stability to the Z-isomer of vinyl
      palladium complex, which subsequently undergoes protodepalladation and leads to
      the Z-enamide selectively. This process is found to be mild and operationally
      simple with broad substrate scope.

PMID- 22978457
TI  - Hypophosphatemia among severely malnourished children with sepsis in Bangladesh.
AB  - BACKGROUND: The interaction between hypophosphatemia (HP) and severe malnutrition
      has received little attention. This study investigated the prevalence, severity,
      and risk factors of HP among severely malnourished children with sepsis in
      Bangladesh. METHODS: Children aged 6-59 months admitted with sepsis to Dhaka
      Hospital from April 2010 to December 2011 were enrolled in the study and divided
      into two groups: severe acute malnutrition (SAM) and non-SAM groups. Plasma
      phosphate and the related biochemical parameters were measured upon admission and
      on the second and fourth days for both groups and the 10th day or discharge day
      for the SAM group. RESULTS: The prevalence of HP (plasma phosphate <3.7 mg/dL)
      was 72.9% and 62.5% (P = 0.26) for 48 SAM and for 56 non-SAM patients,
      respectively; that of moderate-severe HP (phosphate <2 mg/dL) was 25.0% and
      19.6%, respectively (P = 0.51). The plasma phosphate level of 21 SAM patients was
      significantly lower on the second and fourth days than upon admission (P = 0.03,
      P = 0.01, respectively); it then recovered on the 10th day or discharge day. On
      multiple logistic regression analysis, plasma potassium <2.5 mmol/L upon
      admission was found to be a risk factor for moderate or severe HP (adjusted odds
      ratio, 7.21; 95% confidence interval: 1.88-27.7). CONCLUSION: HP is common among
      children with sepsis. Potassium <2.5 mmol/L upon admission is considered a risk
      factor for moderate or severe HP in children with sepsis.

PMID- 22978458
TI  - A systematic review on the effectiveness of prewarming to prevent perioperative
      hypothermia.
AB  - AIMS AND OBJECTIVES: To analyse available research on the effectiveness of
      prewarming to prevent perioperative hypothermia and identify knowledge gaps for
      future research. BACKGROUND: Perioperative hypothermia is common and causes
      complications, such as coagulation and platelet function abnormalities; increased
      cardiac morbidity, surgical site infection, and pressure ulcer incidence levels.
      In this context, several methods have been investigated to prevent perioperative
      hypothermia, including prewarming. Prewarming is defined as the warming of
      peripheral tissues or the skin surface before anaesthetic induction and may
      consist of an active cutaneous warming system or the preoperative administration
      of vasodilation drugs. DESIGN: Systematic review. METHODS: We searched CINAHL,
      EMBASE, Cochrane Register of Controlled Trials and Medline (January 1990-November
      2011) for randomised controlled trials on the effectiveness of prewarming for
      prevention of perioperative hypothermia, published in English, Spanish and
      Portuguese, and involving elective surgery patients aged 18 years or older.
      RESULTS: Of 730 identified studies, only 13 met the inclusion criteria. After
      hand-searching the reference lists of included studies, an additional study was
      identified for a total sample of 14 studies. The results suggest that forced-air
      warming system is effective to reduce hypothermia when applied for the prewarming
      of surgical patients. CONCLUSION: Prewarming patients with the forced-air warming
      system might be effective to reduce perioperative hypothermia, and new studies
      are needed to examine the use of carbon fibre technology. RELEVANCE TO CLINICAL
      PRACTICE: Nurses can use this review to inform decision-making on a prewarming
      programme in the perioperative period. They can also develop research on
      strategies to put in practice prewarming in the surgical context.

PMID- 22978460
TI  - Genotype D of hepatitis B virus and its subgenotypes: An update.
AB  - AIM: The aim of the present study was to systematically and comparatively analyze
      the subgenotypes of genotype D of hepatitis B virus. METHODS: In total, 304
      complete genomes of all genotype D subgenotypes were downloaded from the public
      databases. The sequences were analyzed using nucleotide divergence calculations,
      phylogenetic analysis and bioinformatics to detect amino acids signature motifs
      for each subgenotype and to define their geographical distribution. RESULTS:
      Intragroup divergence ranged from 0.8 +/- 0.5 (%  standard deviation) for
      subgenotype D6 to 3.0 +/- 0.3 for D8. Inter-subgenotype divergence mostly ranged
      4-7.5%. Phylogenetic analysis of genotype D showed separation into six distinct
      clusters (subgenotypes D1, D2, D3/D6, D4, D5 and D7/D8) with good bootstrap
      support. The mean intergroup divergence between D3 and D6 was the lowest and fell
      below the threshold of 4%, which is required to define a subgenotype, suggesting
      that subgenotypes D3 and D6 belong to one subgenotype. "D8" is a genotype D/E
      recombinant, which clusters with D7. A number of signature amino acids were found
      in all four open reading frames that could differentiate the subgenotypes, which
      also showed distinct geographical distribution. CONCLUSION: There are six and not
      eight subgenotypes of D, D1-D6, which can be differentiated by distinct
      clustering with high bootstrap support and signature amino acids. Subgenotypes D3
      and "D6" should be reclassified as a single subgenotype D3 and it would be more
      correct to classify "D8" as a genotype D/E recombinant rather than a subgenotype.

PMID- 22978459
TI  - Fetal brain function in response to maternal alcohol consumption: early evidence
      of damage.
AB  - BACKGROUND: Studies of the adverse neurobehavioral effects of maternal alcohol
      consumption on the fetus have been largely confined to the postnatal period,
      after exposure to alcohol has finished. This study explored the brain function of
      the fetus, at the time of exposure to alcohol, to examine its effect on
      information processing and stability of performance. METHODS: Five groups of
      fetuses, defined by maternal alcohol consumption patterns, were examined: control
      (no alcohol); moderate (5 to 10 units/wk either drunk evenly across the week or
      as a binge, in 2 to 3 days); heavy (20+ units/wk drunk evenly or as a binge).
      Fetal habituation performance was examined on 3 occasions, separated by 7 days,
      beginning at 35 weeks of gestation. The number of trials required to habituate on
      each test session and the difference in performance across test sessions were
      recorded. RESULTS: Fetuses exposed to heavy binge drinking required significantly
      more trials to habituate and exhibited a greater variability in performance
      across all test sessions than the other groups. Maternal drinking, either heavily
      but evenly or moderately as a binge, resulted in poorer habituation, and moderate
      binge drinking resulted in greater variability compared with no, or even,
      drinking. CONCLUSIONS: Decreased information processing, reflected by poorer
      habituation, and increased variability in performance may reflect the initial
      manifestations of structural damage caused by alcohol to the brain. These results
      will lead to a greater understanding of the effects of alcohol on the fetus's
      brain, enable the antenatal identification of fetal alcohol spectrum disorders,
      and lead to the early implementation of better management strategies.

PMID- 22978462
TI  - Transplantation material bovine pericardium: biomechanical and immunogenic
      characteristics after decellularization vs. glutaraldehyde-fixing.
AB  - BACKGROUND: Today, bovine pericardium (BP) is extensively investigated as a
      biomaterial for the generation of various bioimplants. But despite the commercial
      distribution, and the development of methods either to remove (decellularization)
      or to mask (chemical cross-linking, for example by glutaraldehyde [GA] treatment)
      the xenogeneic antigen epitopes, yet questions around the immunogenic reactivity
      of BP remain. The aim of this study is the comparison of crucial tissue
      characteristics, that is, biomechanical properties, the presence of alphaGal
      epitopes, and residual DNA in acellular vs. GA-fixed BP. METHODS: Bovine
      pericardium was either cross-linked with 0.6% GA or decellularized according to
      two common protocols using either sodium dodecyl sulfate (SDS) and desoxycholic
      acid (DCA) or trypsin and ethylenediaminetetraacetic acid (EDTA). The resulting
      extracellular matrix was prone to one-dimensional tensile testing. The tissue
      content for alphaGal was evaluated by immunoblotting, and residual DNA was
      determined by a commercial assay. Untreated BP served as control. RESULTS: In
      contrast to previous reports, we found a pronounced decrease in the elastic
      modulus (E-Modulus) for common GA treatment and overall smaller values for the
      elastic moduli after decellularization (P < 0.05). In parallel, we observed an
      overall increased ultimate elongation of acellular and cross-linked BP, although
      ultimate stress values did not significantly differ. SDS/DCA decellularized BP
      revealed a dramatic reduction in the DNA content and an almost complete removal
      of alphaGal epitopes, whereas the trypsin/EDTA protocol retained a residual DNA
      content of almost 50% and with a great trail of alphaGal signal. GA-treated
      tissue had a remarkable content of DNA and alphaGal. CONCLUSIONS: Although
      chemically fixated BP is clinically still in wide use, for example, for
      biological heart valve engineering, our results suggest that an improved
      biomaterial preparation may be provided by appropriate decellularization. SDS/DCA
      decellularized BP shows similar biomechanical characteristics as GA treatment,
      paired with reduced potential immunogenic reactivity. Furthermore, decellularized
      BP holds the potential of cellular repopulation in vivo or in vitro, to enable an
      endogenous regenerative capacity in contrast to the toxic effects of GA fixing.

PMID- 22978463
TI  - Identification of HLA-DR4-restricted immunogenic peptide derived from xenogenic
      porcine major histocompatibility complex class I molecule.
AB  - Indirect recognition of xenoantigens has been implicated as the major mechanism
      underlying xenospecific CD4+ T-cell activation in chronic rejection. We
      identified swine leukocyte antigen (SLA)-derived immunogenic peptides that are
      presented in the context of human HLA-DR4 molecules. The SLA class I-derived
      peptides that bind HLA-DRB1*0401, a representative of the DR4 supertype, were
      predicted using a computer-assisted algorithm. The candidate peptides were
      synthesized, and their binding capacities to HLA-DRB1*0401 were compared in a
      competitive ELISA using biotinylated hemagglutinin reporter peptides [HA(307
      319)]. Peptide-11 (LRSWTAADTAAQISK) was determined to exhibit the most potent
      binding capacity to HLA-DRB1*0401 in vitro and thus selected for in vivo
      immunization. Immunization of HLA-DRB1*0401-transgenic mice with peptide-11
      elicited potent CD4+ Th1 responses. Peptide-11 shares homology to alpha2 domains
      of three SLA-1 alleles, six SLA-2 alleles, and 14 SLA-3 alleles. Thus, this study
      has important implications not only for the identification of an immunogenic
      indirect epitope shared by diverse SLA class I alleles, but also for the
      development of epitope-specific immunoregulation strategies.

PMID- 22978464
TI  - Xenotransplantation literature update, July-August 2012.

PMID- 22978461
TI  - Do mesenchymal stem cells function across species barriers? Relevance for
      xenotransplantation.
AB  - BACKGROUND: Allogeneic mesenchymal stem (stromal) cells (MSC) are a promising
      therapy for various pathological conditions. Genetically modified pig MSC have
      been demonstrated to downregulate the human T-cell response to pig antigens in
      vitro. Before genetically modified pig MSC can be used clinically, however,
      evidence needs to be provided to indicate whether they will survive in a human
      (xenogeneic) host. LITERATURE SEARCH AND RESULTS: A literature search through the
      end of 2011 identified 94 reports of the in vivo cross-species administration of
      MSC in a variety of experimental models. The majority (n = 89) involved the use
      of human MSC in various other species, with an occasional study using pig, rat,
      or guinea-pig MSC. When human MSC were used, they were largely derived from the
      bone marrow, adipose tissue, or umbilical cord blood. The routes of
      administration were varied, although almost half of the studies utilized the
      intravenous route. In 88 experiments (93.6%), there was evidence that the MSC
      engrafted and functioned across the species barrier, and in only six cases (6.4%)
      was there evidence of failure to function. Importantly, MSC function was
      confirmed in several different cross-species models. For example, human MSC
      functioned in no fewer than seven different recipient species. CONCLUSIONS: The
      data provided by this literature search strengthen the hypothesis that pig MSC
      will function satisfactorily in a different species, for example, humans. The
      data also suggest that our own in vitro observations on the efficacy of pig MSC
      in downregulating the strength of the human T-cell response to pig antigens will
      likely be reproduced in vivo in pre-clinical large animal models and in clinical
      trials.

PMID- 22978465
TI  - Multiple system atrophy with early cognitive deficits: a case report.
AB  - We present the case of a patient with multiple system atrophy with predominant
      cerebellar ataxia (MSA-C) in the early stage of the disease, who was assessed
      using a comprehensive neuropsychological test battery. Many studies have found
      cognitive deficits in MSA patients assessed after 2-3 years, but not in the first
      stages of the disease. The aim of this paper is to stress the importance of a
      complete neuropsychological assessment, even at the initial stage of the disease,
      when instrumental examinations are not able to show cortical involvement and
      daily life activities have not been affected. The neuropsychological tests
      examined general cognition, verbal and visual memory, visuospatial and
      constructional ability, language, executive function, depression and functional
      autonomy. Results showed cognitive deficits in executive functions, above all in
      the control and inhibition of automatic response, planning and reasoning
      abilities, memory and visuoconstructional functions. However, these problems did
      not affect the patient's autonomy in everyday life. MRI scan showed the
      involvement of the cerebellum and the fibers of the pons and raphe, with normal
      cerebral ventricles and sulci. The cognitive deficits in our patient could be
      explained by a disruption in cerebrocerebellum connections between the frontal
      areas and the cerebellar structures. These results show that a more comprehensive
      cognitive evaluation is necessary to detect early the onset of neuropsychological
      deficits, also in order to begin in time adequate rehabilitation programs. 

PMID- 22978467
TI  - Identification of a novel HLA-B allele HLA-B*13:20 in a Chinese individual.
AB  - The HLA-B*13:20 allele differs from the closest matching allele B*13:01:01 by one
      nucleotide substitution in exon 3 at nt 527 (T->A).

PMID- 22978466
TI  - Anxiety symptoms among Chinese nurses and the associated factors: a cross
      sectional study.
AB  - BACKGROUND: Nurses are an indispensable component of the work force in the health
      care system. However, many of them are known to work in a stressful environment
      which may affect their mental well-being; the situation could be worse in rapidly
      transforming societies such as China. The purpose of this study was to
      investigate anxiety symptoms and the associated factors in Chinese nurses working
      in public city hospitals. METHODS: A cross-sectional survey was performed for
      Chinese nurses in public city hospitals of Liaoning Province, northeast China.
      Seven hospitals in different areas of the province were randomly selected for the
      study. The Zung Self-Rating Anxiety Scale was used to measure anxiety symptoms.
      Effort-reward imbalance questionnaire and Job Content Questionnaire were used to
      assess the work stressors. Univariate analysis and stepwise multivariate logistic
      regression analysis were used to identify the factors associated with anxiety
      symptoms. RESULTS: All registered nurses in the seven city hospitals, totaling
      1807 registered nurses were surveyed. Of the returned questionnaires, 1437 were
      valid (79.5%) for analysis. Utilizing the total raw score >= 40 as the cut-off
      point, the prevalence of anxiety symptoms in these nurses was 43.4%. Demographic
      factors (education, chronic disease and life event), lifestyle factors (regular
      meals and physical exercise), work conditions (hospital grade, job rank, monthly
      salary, nurse-patient relationships, job satisfaction and intention of leaving),
      job content (social support and decision latitude), effort-reward imbalance and
      overcommitment were all significantly related to the anxiety symptoms.
      Multivariate logistic regression analysis showed main factors associated with
      anxiety symptoms were lower job rank (OR 2.501), overcommitment (OR 2.018),
      chronic diseases (OR 1.541), worse nurse-patient relationship (OR 1.434), higher
      social support (OR 0.573), lower hospital grade (OR 0.629), taking regular meals
      (OR 0.719) and higher level of job satisfaction (OR 0.722). CONCLUSIONS: A large
      proportion of Chinese nurses working in public city hospitals had anxiety
      symptoms, which warrants immediate investigation and intervention from the
      hospital administrators. Meanwhile, results of the study suggest that proper
      counseling, promotion of healthy lifestyle behavior and improvements to the
      social environment in the work place may be helpful toward reducing or preventing
      the anxiety symptoms.

PMID- 22978468
TI  - Structure-dependent interactions between alkali feldspars and organic compounds:
      implications for reactions in geologic carbon sequestration.
AB  - Organic compounds in deep saline aquifers may change supercritical CO(2)
      (scCO(2))-induced geochemical processes by attacking specific components in a
      mineral's crystal structure. Here we investigate effects of acetate and oxalate
      on alkali feldspar-brine interactions in a simulated geologic carbon
      sequestration (GCS) environment at 100 atm of CO(2) and 90  degrees C. We show
      that both organics enhance the net extent of feldspar's dissolution, with oxalate
      showing a more prominent effect than acetate. Further, we demonstrate that the
      increased reactivity of Al-O-Si linkages due to the presence of oxalate results
      in the promotion of both Al and Si release from feldspars. As a consequence, the
      degree of Al-Si order may affect the effect of oxalate on feldspar dissolution: a
      promotion of ~500% in terms of cumulative Si concentration was observed after 75
      h of dissolution for sanidine (a highly disordered feldspar) owing to oxalate,
      while the corresponding increase for albite (a highly ordered feldspar) was ~90%.
      These results provide new insights into the dependence of feldspar dissolution
      kinetics on the crystallographic properties of the mineral under GCS conditions.

PMID- 22978469
TI  - Trypsin inhibitory activity and gel-enhancing effect of sarcoplasmic proteins
      from common carp.
AB  - Proteinase inhibitory activity of sarcoplasmic protein (SP) extracted from common
      carp (Cyprinus carpio) muscle and its gel-improving ability were investigated.
      SPs displayed 89% and 54% inhibitory activity toward trypsin at 40 and 65 
      degrees C, respectively. Protein bands with molecular mass of 69, 50, 44, 41, and
      35 kDa appeared on trypsin inhibitory activity staining under nonreducing
      condition when incubated at 40  degrees C, while 2 protein bands at 54 and 35 kDa
      were observed at 65  degrees C. Addition of SP at 0.18 g protein/100 g increased
      textural properties of threadfin bream surimi gel. However, when SP was added in
      combination with various CaCl(2) concentrations (0.1% to 0.5%) it did not further
      improve textural properties as compared to the addition of SP alone. Retention of
      myosin heavy chain of threadfin bream surimi was greater with the addition of SP.
      These results indicated that the gel-enhancing effect of common carp SP was due
      to the inhibitory activity toward endogenous trypsin-like proteinases in
      threadfin bream surimi. PRACTICAL APPLICATION: Sarcoplasmic protein from common
      carp muscle could be used as a functional protein ingredient that minimizes
      muscle proteolysis and improves textural properties of surimi containing trypsin
      like endogenous proteinases.

PMID- 22978470
TI  - Diversity and evolution of multiple orc/cdc6-adjacent replication origins in
      haloarchaea.
AB  - BACKGROUND: While multiple replication origins have been observed in archaea,
      considerably less is known about their evolutionary processes. Here, we performed
      a comparative analysis of the predicted (proved in part) orc/cdc6-associated
      replication origins in 15 completely sequenced haloarchaeal genomes to
      investigate the diversity and evolution of replication origins in halophilic
      Archaea. RESULTS: Multiple orc/cdc6-associated replication origins were predicted
      in all of the analyzed haloarchaeal genomes following the identification of
      putative ORBs (origin recognition boxes) that are associated with orc/cdc6 genes.
      Five of these predicted replication origins in Haloarcula hispanica were
      experimentally confirmed via autonomous replication activities. Strikingly,
      several predicted replication origins in H. hispanica and Haloarcula marismortui
      are located in the distinct regions of their highly homologous chromosomes,
      suggesting that these replication origins might have been introduced as parts of
      new genomic content. A comparison of the origin-associated Orc/Cdc6 homologs and
      the corresponding predicted ORB elements revealed that the replication origins in
      a given haloarchaeon are quite diverse, while different haloarchaea can share a
      few conserved origins. Phylogenetic and genomic context analyses suggested that
      there is an original replication origin (oriC1) that was inherited from the
      ancestor of archaea, and several other origins were likely evolved and/or
      translocated within the haloarchaeal species. CONCLUSION: This study provides
      detailed information about the diversity of multiple orc/cdc6-associated
      replication origins in haloarchaeal genomes, and provides novel insight into the
      evolution of multiple replication origins in Archaea.

PMID- 22978472
TI  - Pathological significance of epidermal growth factor receptor expression and
      amplification in human gliomas.
AB  - AIMS: To investigate epidermal growth factor receptor (EGFR) expression and
      amplification in gliomas and to assess their association with survival. METHODS
      AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridization were
      performed to analyse EGFR status in 158 cases of primary glioma. Kaplan-Meier
      survival and Cox regression analyses were performed to analyse the prognosis of
      patients. Overexpression of EGFR and expression of EGFR variant III (EGFRvIII)
      were found in 102 cases (64.6%) and 47 cases (29.7%), respectively.
      Overexpression of EGFR was significantly correlated with World Health
      Organization (WHO) grade and Karnofsky performance score (KPS) (both P < 0.05).
      Expression of EGFRvIII was significantly correlated with WHO grade, gender, age,
      and KPS (all P < 0.05). EGFR amplification was found in 46 cases (29.1%), and was
      significantly correlated with WHO grade, age, KPS and EGFR overexpression (all P
      < 0.05). Cox multifactor analysis showed that EGFR amplification was an
      independent unfavourable prognostic factor for human gliomas at all ages, and
      EGFRvIII was an independent prognostic factor in patients older than 60 years.
      CONCLUSION: EGFR amplification and EGFRvIII expression were associated with an
      unfavourable prognosis for patients of all ages, and for those older than 60
      years, respectively. The differing significance of EGFR status in young and old
      glioma patients and its impact on prognosis needs further study.

PMID- 22978473
TI  - Effect of eczema on the association between season of birth and food allergy in
      Japanese children.
AB  - BACKGROUND: Food allergy (FA) in childhood has been shown to be more prevalent in
      those born in autumn and winter. The mechanisms of this season-of-birth effect
      remain unclear, although shortage of vitamin D during infancy has been considered
      one possible mechanism. The purpose of this study was to investigate the effect
      of eczema on the season-of-birth effect on FA in infancy. METHODS: A
      questionnaire survey on the prevalence of allergic diseases was completed by the
      parents of 14 669 Japanese schoolchildren, aged 7-15 years, in Kyoto City, Japan.
      Logistic regression models were constructed to compare the prevalence of FA in
      infancy according to season of birth. RESULTS: Those born in autumn and winter
      had a significantly higher prevalence of FA in infancy compared to those born in
      spring and summer in a multivariate model (4.8% vs 3.6%, P = 0.001). The
      difference, however, was no longer significant when eczema before 6 months was
      included as either an additional or only confounding factor. The difference among
      those with and without eczema before 6 months was further analyzed, and it was
      found that, in both groups, there was no difference between those born in spring
      and summer and those born in autumn and winter. CONCLUSIONS: The season-of-birth
      effect on FA in infancy was significantly affected by the existence of eczema
      before 6 months in Japanese children. Eczema before 6 months may be the factor
      directly related to the season-of-birth effect on FA in infancy.

PMID- 22978471
TI  - Regulation of the intrinsic apoptosis pathway by reactive oxygen species.
AB  - SIGNIFICANCE: The intrinsic apoptosis pathway is conserved from worms to humans
      and plays a critical role in the normal development and homeostatic control of
      adult tissues. As a result, numerous diseases from cancer to neurodegeneration
      are associated with either too little or too much apoptosis. RECENT ADVANCES: B
      cell lymphoma-2 (BCL-2) family members regulate cell death, primarily via their
      effects on mitochondria. In stressed cells, proapoptotic BCL-2 family members
      promote mitochondrial outer membrane permeabilization (MOMP) and cytochrome c
      (cyt c) release into the cytoplasm, where it stimulates formation of the
      "apoptosome." This large, multimeric complex is composed of the adapter protein,
      apoptotic protease-activating factor-1, and the cysteine protease, caspase-9.
      Recent studies suggest that proteins involved in the processes leading up to (and
      including) formation of the apoptosome are subject to various forms of post
      translational modification, including proteolysis, phosphorylation, and in some
      cases, direct oxidative modification. CRITICAL ISSUES: Despite intense
      investigation of the intrinsic pathway, significant questions remain regarding
      how cyt c is released from mitochondria, how the apoptosome is formed and
      regulated, and how caspase-9 is activated within the complex. FUTURE DIRECTIONS:
      Further studies on the biochemistry of MOMP and apoptosome formation are needed
      to understand the mechanisms that underpin these critical processes, and novel
      animal models will be necessary in the future to ascertain the importance of the
      many posttranslational modifications reported for BCL-2 family members and
      components of the apoptosome.

PMID- 22978474
TI  - Natural history, management, and outcomes of peripartum cardiomyopathy: an Irish
      single-center cohort study.
AB  - AIM: To describe the natural history, management and outcomes of peripartum
      cardiomyopathy (PPCM) in an unselected Northern European population. METHODS: A
      retrospective single-center observational study was performed at a tertiary
      referral heart failure and transplantation unit. Outcomes measured were baseline
      demographics, clinical presentation, course, and treatment. Echocardiographic
      findings were compared at baseline, 2 months, and 6 months. RESULTS: Twelve cases
      of PPCM were identified between 2002 and 2008. Mean age was 34.7 years. Nine
      patients were multiparous and nine had preeclampsia. Ten patients presented in
      the first week postpartum. Two patients required inotropic support. Mean ejection
      fraction (EF) at presentation was 27% (SD = 8%) which improved to 47% (SD = 13%)
      at 6 months. At this time, 10 patients were asymptomatic and 6 had recovered
      normal cardiac function. Left ventricular (LV) function improved but did not
      reach normal limits in five cases. One case with persistent severe LV dysfunction
      required cardiac transplantation. One patient suffered an arrhythmic death
      several years after the 6 months follow-up period. CONCLUSIONS: PPCM is a rare
      condition. With appropriate therapy, a good clinical outcome is common but not
      universal. Continued deterioration requiring ventricular support and cardiac
      transplantation can occur. In our cohort, older maternal age, multiparity, and
      preeclampsia appeared to be risk factors.

PMID- 22978475
TI  - Postgraduate career intentions of medical students and recent graduates in
      Malawi: a qualitative interview study.
AB  - BACKGROUND: In 2004, the Malawian Ministry of Health declared a human resource
      crisis and launched a six year Emergency Human Resources Programme. This included
      salary supplements for key health workers and a tripling of doctors in training.
      By 2010, the number of medical graduates had doubled and significantly more
      doctors were working in rural district hospitals. Yet there has been little
      research into the views of this next generation of doctors in Malawi, who are
      crucial to the continuing success of the programme. The aim of this study was to
      explore the factors influencing the career plans of medical students and recent
      graduates with regard to four policy-relevant aspects: emigration outside Malawi;
      working at district level; private sector employment and postgraduate
      specialisation. METHODS: Twelve semi-structured interviews were conducted with
      fourth year medical students and first year graduates, recruited through
      purposive and snowball sampling. Key informant interviews were also carried out
      with medical school faculty. Recordings were transcribed and analysed using a
      framework approach. RESULTS: Opportunities for postgraduate training emerged as
      the most important factor in participants' career choices, with specialisation
      seen as vital to career progression. All participants intended to work in Malawi
      in the long term, after a period of time outside the country. For nearly all
      participants, this was in the pursuit of postgraduate study rather than higher
      salaries. In general, medical students and young doctors were enthusiastic about
      working at district level, although this is curtailed by their desire for
      specialist training and frustration with resource shortages. There is currently
      little intention to move into the private sector. CONCLUSIONS: Future resourcing
      of postgraduate training opportunities is crucial to preventing emigration as
      graduate numbers increase. The lesser importance put on salary by younger doctors
      may be an indicator of the success of salary supplements. In order to retain
      doctors at district levels for longer, consideration should be given to the
      introduction of general practice/family medicine as a specialty. Returning
      specialists should be encouraged to engage with younger colleagues as role models
      and mentors.

PMID- 22978477
TI  - Prediction of a favorable clinical course in hepatitis C virus carriers with
      persistently normal serum alanine aminotransferase levels: A long-term follow-up
      study.
AB  - AIM: This study examined serum alanine aminotransferase (ALT) levels at first
      visit and their relationship with long-term normal serum ALT levels in hepatitis
      C virus (HCV) carriers with persistently normal ALT (PNALT). METHODS: HCV
      carriers with PNALT were identified as those patients with positivity of serum
      HCV RNA, ALT levels of 30 IU/L or less over a 12-month period on at least three
      different occasions, platelet count of more than 15 * 10(4)  MUl/mL and body mass
      index of 30 kg/m(2) or less. Outcome was retrospectively studied in 49 HCV
      carriers with PNALT, who were followed up for more than 10 years. RESULTS: During
      the mean follow-up period of 14.7 +/- 2.5 years, ALT levels of 30 IU/L or less
      were preserved in only eight patients (8/49; 16.3%). Among the 17 patients with
      initial ALT levels of 19 IU/L or less, nine patients remained with ALT levels of
      30 IU/L or less after 10 years (9/17; 52.9%). The probability of ALT levels in
      PNALT being maintained at 30 IU/L or less was significantly higher (P = 0.001) in
      these patients than in those with initial ALT levels of 20 IU/L or more (n = 32).
      Abnormal ALT levels were more common in female PNALT patients aged 45-55 years,
      which is usually the time of menopause onset. CONCLUSION: Because antiviral
      therapy in the treatment of chronic hepatitis C is rapidly advancing, waiting for
      more effective and safer treatments may be an option. The results of this study
      provide an important insight into this issue.

PMID- 22978476
TI  - Effect of electroacupuncture on opioid consumption in patients with chronic
      musculoskeletal pain: protocol of a randomised controlled trial.
AB  - BACKGROUND: Chronic musculoskeletal pain is common and has been increasingly
      managed by opioid medications, of which the long-term efficacy is unknown.
      Furthermore, there is evidence that long-term use of opioids is associated with
      reduced pain control, declining physical function and quality of life, and could
      hinder the goals of integrated pain management. Electroacupuncture (EA) has been
      shown to be effective in reducing postoperative opioid consumption. Limited
      evidence suggests that acupuncture could assist patients with chronic pain to
      reduce their requirements for opioids.The proposed research aims to assess if EA
      is an effective adjunct therapy to standard pain and medication management in
      reducing opioids use by patients with chronic musculoskeletal pain. METHODS: In
      this multicentre, randomised, sham-acupuncture controlled, three-arm clinical
      trial, 316 patients regularly taking opioids for pain control and meeting the
      defined selection criteria will be recruited from pain management centres and
      clinics of primary care providers in Victoria, Australia. After a four-week run
      in period, the participants are randomly assigned to one of three treatment
      groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants
      receive routine pain medication management delivered and supervised by the trial
      medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are
      delivered over 10 weeks. Upon completion of the acupuncture treatment period,
      there is a 12-week follow-up. In total, participants are involved in the trial
      for 26 weeks. Outcome measures of opioid and non-opioid medication consumption,
      pain scores and opioid-related adverse events are documented throughout the
      study. Quality of life, depression, function, and attitude to pain medications
      are also assessed. DISCUSSION: This randomised controlled trial will determine
      whether EA is of significant clinical value in assisting the management of
      debilitating chronic pain by reducing opioids consumption and their associated
      adverse events, as well as improving the quality of life for those with chronic
      pain. Such an outcome will provide the rationale for including EA into
      multidisciplinary programmes for effective management of chronic musculoskeletal
      pain. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry
      (ACTRN12609000676213)http://www.anzctr.org.au/trial_view.aspx?ID=308008.

PMID- 22978478
TI  - Markers of bone resorption and formation during abstinence in male alcoholic
      patients.
AB  - BACKGROUND: Reduced bone mineral density (BMD) is commonly found in alcohol
      dependent patients. Many risk factors have been reported, yet the course of
      markers of bone formation and resorption in abstinent alcoholic patients have not
      received much attention. METHODS: In a prospective longitudinal study, we
      investigated BMD in male abstinent inpatients of an alcohol rehabilitation clinic
      aged 21 to 50 years at baseline and after 8 weeks of treatment. At baseline and
      at week 8, all patients had blood drawn for the analysis of liver function tests,
      calcium, phosphate, parathormone, 25-hydroxyvitamin D, osteocalcin (OC), serum
      crosslaps, sex hormones, and prolactin. BMD was determined by dual X-ray
      absorptiometry in the lumbar spine and the proximal right femur. We also
      determined the amount of physical activity prior to inpatient treatment by using
      the International Physical Activity Questionnaire (IPAQ). RESULTS: Low BMD was
      found in 15.1% of the patients for the lumbar spine, in 5.7% for the femoral
      neck, and in 1.9% for the total hip. BMD differed significantly from normal
      values, in the lumbar spine and in the femoral neck. At baseline, crosslaps were
      elevated in 34% of the patients, while OC levels were lowered in 17%. Over the
      course of the 8 weeks, we found a significant increase in OC plasma levels,
      indicating a higher rate of bone formation during continuous abstinence. There
      were also positive correlations between IPAQ scores and BMD as reflected by Z
      scores in all regions, pointing to a protective effect of physical activity.
      CONCLUSIONS: In summary, this report confirms earlier cross-sectional studies of
      lowered BMD in alcoholic noncirrhotic men. We could also demonstrate that the
      initial imbalance between bone formation and resorption seems to adjust toward a
      balance between the two during abstinence.

PMID- 22978479
TI  - Changing the direction of intramolecular electron transfer in oxidized dipeptides
      containing tryptophan and tyrosine.
AB  - Intramolecular electron transfer (IET) in the oxidized dipeptide Tyr-Trp was
      investigated in the pH range from 1.0 to 3.1 by the method of time-resolved
      chemically induced dynamic nuclear polarization. The results were compared with
      data obtained earlier for Trp-Tyr. Surprisingly, it was found that the direction
      of IET changes with the order of the amino acid residues in the peptide. For Tyr
      Trp, the rate constant of electron transfer from tyrosine residue to tryptophanyl
      cation radical is below 1.2 * 10(4) s(-1), whereas for Trp-Tyr, the value of this
      rate constant is 5.5 * 10(5) s(-1). Conversely, for oxidized Tyr-Trp at pH range
      2.1 and lower, electron transfer from tryptophan residue to tyrosyl radical is
      observed. The rate constant of this reaction is proportional to the concentration
      of protons in aqueous solution, and at pH 1.0 is equal to 6.5 * 10(5) s(-1). The
      change in direction of IET observed for oxidized Tyr-Trp dipeptide is presumably
      due to the positive charge at the N-terminal amino group of the peptide, which
      promotes electron transfer in the direction of the N-terminus.

PMID- 22978480
TI  - Chemical composition of 13 commercial soybean samples and their antioxidant and
      anti-inflammatory properties.
AB  - A total of 13 commercial soybean samples were investigated and compared for their
      tocopherol and carotenoid compositions, fatty acid profile, total phenolic
      content (TPC), isoflavone and sterol compositions, and free radical scavenging
      properties. Free radical scavenging activities were estimated against peroxyl,
      hydroxyl, and ABTS(*) (+) radicals. The commercial soybean samples differed in
      their chemical compositions and health properties. Among the tested samples, CN
      DB soybean showed the highest TPC and antioxidant activities and the greatest
      amount of total isoflavones and lutein and tocopherol contents. In addition, four
      of the soybean samples were further tested for their potential anti-inflammatory
      activity. The four samples behaved differently in suppressing the IL-1beta, IL-6,
      and COX-2 mRNA expressions, suggesting their different potential of anti
      inflammatory activities. The results from this study suggested a need of improved
      quality control and measurement system to better reflect the health properties of
      commercial soybeans for general consumers and food manufacturers to improve the
      use of this important food ingredient. 

PMID- 22978481
TI  - Development of new in vivo imaging methodology and system for the rapid and
      quantitative evaluation of the visual appearance of facial skin firmness.
AB  - BACKGROUND/AIMS: Lack of firmness is a key sign of skin aging, but there are no
      methods for quantifying the firmness of facial skin as perceived visually. The
      objective of this study was to develop a convenient and accurate method for this
      purpose. METHODS: A compact imaging system (Magic Ring) was developed to capture
      images of facial skin. By using an image-analysis algorithm, the number of facial
      lines and their direction were analyzed to give an index termed the 'Ageless
      Vector'. Correlations between the Ageless Vector and visually perceived facial
      skin firmness, mechanical skin firmness (R5), and actual age were examined for
      108 Asian females. The technique was also used to assess the effects of a 14-day
      skin-moisturization regimen in 47 Asian female volunteers. RESULTS: The Ageless
      Vector showed highly significant correlation with visually perceived skin
      firmness (r = 0.816) and significant correlation with mechanical skin firmness
      (R5) (r = -0.775). Skin moisturization significantly improved both the Ageless
      Vector (P < 0.05) and the visual grading of apparent skin firmness. CONCLUSIONS:
      We confirmed by two clinical studies that the imaging methodology using the
      Ageless Vector and the Magic Ring facial-imaging system was sufficiently
      sensitive to permit the measurement of apparent visible skin firmness and that it
      is an excellent method suitable for practical in vivo applications.

PMID- 22978482
TI  - Surface-enhanced Raman spectroscopy to probe photoreaction pathways and kinetics
      of isolated reactants on surfaces: flat versus curved substrates.
AB  - We identify and control the photoreaction paths of self-assembled monolayers
      (SAMs) of thiolate-linked anthracene phenylethynyl molecules on Au substrate
      surfaces, and study the effects of nanoscale morphology of substrates on
      regioselective photoreactions. Two types of morphologies, atomically flat and
      curved, are produced on Au surfaces by controlling substrate structure and metal
      deposition. We employ surface-enhanced Raman spectroscopy (SERS), combined with
      Raman mode analyses using density functional theory, to identify the different
      photoreaction paths and to track the photoreaction kinetics and efficiencies of
      molecules in monolayers. The SAMs on curved surfaces exhibit dramatically lower
      regioselective photoreaction kinetics and efficiencies than those on atomically
      flat surfaces. This result is attributed to the increased intermolecular
      distances and variable orientations on the curved surfaces. Better understanding
      of the morphological effects of substrates will enable control of nanoparticle
      functionalization in ligand exchange in targeted delivery of therapeutics and
      theranostics and in catalysis.

PMID- 22978483
TI  - High-molecular-weight kininogen and the risk of a myocardial infarction and
      ischemic stroke in young women: the RATIO case-control study.

PMID- 22978484
TI  - Oceanographic drivers of offspring abundance may increase or decrease
      reproductive variance in a temperate marine fish.
AB  - In species that reproduce into uncertain environments, the relationship between
      mean reproductive success (the abundance of new recruits) and the variance in
      reproductive success (whether adults contribute disproportionally more offspring)
      may not be straightforward because of stochastic environmental processes that
      create high variance in reproductive success among adults. In this study, we
      investigated the relationships between oceanography, reproductive success and
      reproductive variance in the black rockfish, Sebastes melanops, a long-lived
      temperate reef fish with pelagic larvae. We quantified black rockfish
      recruitment, genetic diversity and growth rates from otolith microstructure over
      5 years (2005-2009) during which oceanographic conditions differed. We used cross
      correlations to determine windows of time during which oceanographic variables
      were significantly correlated with the resulting abundance or genetic diversity
      of recruits. We found that warmer ocean temperatures were positively correlated
      with the abundance of recruits, as well as the effective number of breeders. In
      contrast, the strength of coastal upwelling during settlement was positively
      correlated with the annual abundance of new recruits, but was negatively
      correlated with the effective number of breeders. Larval growth rates were
      explained substantially more by temperature than by upwelling and suggested that
      temperature affected survival through growth, while upwelling affected survival
      through transport. Our results indicated that cold ocean temperatures and intense
      upwelling caused sweepstakes-like processes to operate on black rockfish
      populations, despite high abundances of recruits. We propose that a decoupling of
      the mean and variance in reproductive success may be characteristic of organisms
      that reproduce into uncertain environments.

PMID- 22978485
TI  - Primary yolk sac tumor of seminal vesicle: a case report and literature review.
AB  - BACKGROUND: Yolk sac tumor (endodermal sinus tumor) is a rare malignant germ cell
      tumor arising in the testis or ovary. Extragonadal yolk sac tumor is even rarer
      and has only been described in case reports. Due to the rarity of the tumors, the
      appropriately optimal treatment remains unclear. We report a case of yolk sac
      tumor in the seminal vesicle. CASE: A 38-year-old Asian male presented with gross
      hematuria and hemospermia. Transrectal ultrasound scan showed a solid mass in the
      left seminal vesicle and the scrotal sonography showed no abnormalities.
      Bilateral seminal vesicles were resected, and histopathological examination
      showed a typical pattern of yolk sac tumor (YST). The patient responded poorly to
      comprehensive treatment of radiotherapy, chemotherapy and surgeries, developed
      systemic multiple metastases, and died of cachexia one and half years after
      diagnosis.

PMID- 22978486
TI  - Posterior transjugular and transcervical approach for glomus tumours within the
      head and neck.
AB  - Glomus tumours within the head and neck are highly vascular in nature and are
      surrounded by vital neurovascular structures. The aim of this study is to review
      the step-by-step surgical techniques for a posterior transjugular approach and
      transcervical approach and to clarify the advantages of these approaches in the
      treatment of glomus tumours within the head and neck. The advantage of these
      approaches is that a wide operative field from the jugular bulb to the cervical
      portion can be obtained. In addition, the bloodless operative field that is
      achieved by the preoperative embolisation appeared to contribute to reducing the
      risk of cranial nerve injury.

PMID- 22978488
TI  - Review of spinal neuroectodermal tumor.
AB  - Primary spinal primitive neuroectodermal tumors (PNETs) are rare tumors. Most of
      these tumors occur in children and young adults. To date, 47 cases of primary
      spinal PNET have been reported in the literature. These tumors are highly
      aggressive with rapid growth. Review of the literature shows that the overall
      prognosis of PNETs of spinal cord is very poor even with adequate surgery,
      radiotherapy and chemotherapy. All the cases reported to date are reviewed in
      terms of surgical treatment, adjuvant therapy and outcome and the experience with
      two of these cases are described. Both cases were thoracic extradural ones with
      intrathoracic extension through intervertebral foramina resembling neurofibroma.
      Both cases underwent gross total removal of intraspinal and thoracic component.
      Post-operatively both underwent cranio-spinal radiotherapy. One patient died
      after a post-operative period of 4 months and the other one is still alive 8
      months after surgery, radiotherapy and chemotherapy.

PMID- 22978489
TI  - Modeling As(III) oxidation and removal with iron electrocoagulation in
      groundwater.
AB  - Understanding the chemical kinetics of arsenic during electrocoagulation (EC)
      treatment is essential for a deeper understanding of arsenic removal using EC
      under a variety of operating conditions and solution compositions. We describe a
      highly constrained, simple chemical dynamic model of As(III) oxidation and
      As(III,V), Si, and P sorption for the EC system using model parameters extracted
      from some of our experimental results and previous studies. Our model predictions
      agree well with both data extracted from previous studies and our observed
      experimental data over a broad range of operating conditions (charge dosage rate)
      and solution chemistry (pH, co-occurring ions) without free model parameters. Our
      model provides insights into why higher pH and lower charge dosage rate
      (Coulombs/L/min) facilitate As(III) removal by EC and sheds light on the debate
      in the recent published literature regarding the mechanism of As(III) oxidation
      during EC. Our model also provides practically useful estimates of the minimum
      amount of iron required to remove 500 MUg/L As(III) to <50 MUg/L. Parameters
      measured in this work include the ratio of rate constants for Fe(II) and As(III)
      reactions with Fe(IV) in synthetic groundwater (k(1)/k(2) = 1.07) and the
      apparent rate constant of Fe(II) oxidation with dissolved oxygen at pH 7 (k(app)
      = 10(0.22) M(-1)s(-1)).

PMID- 22978490
TI  - Barriers, facilitators and preferences for the physical activity of school
      children. Rationale and methods of a mixed study.
AB  - BACKGROUND: Physical activity interventions in schools environment seem to have
      shown some effectiveness in the control of the current obesity epidemic in
      children. However the complexity of behaviors and the diversity of influences
      related to this problem suggest that we urgently need new lines of insight about
      how to support comprehensive population strategies of intervention. The aim of
      this study was to know the perceptions of the children from Cuenca, about their
      environmental barriers, facilitators and preferences for physical activity.
      METHODS/DESIGN: We used a mixed-method design by combining two qualitative
      methods (analysis of individual drawings and focus groups) together with the
      quantitative measurement of physical activity through accelerometers, in a
      theoretical sample of 121 children aged 9 and 11 years of schools in the province
      of Cuenca, Spain. CONCLUSIONS: Mixed-method study is an appropriate strategy to
      know the perceptions of children about barriers and facilitators for physical
      activity, using both qualitative methods for a deeply understanding of their
      points of view, and quantitative methods for triangulate the discourse of
      participants with empirical data. We consider that this is an innovative approach
      that could provide knowledges for the development of more effective interventions
      to prevent childhood overweight.

PMID- 22978491
TI  - Genome sequencing and genetic breeding of a bioethanol Saccharomyces cerevisiae
      strain YJS329.
AB  - BACKGROUND: Environmental stresses and inhibitors encountered by Saccharomyces
      cerevisiae strains are the main limiting factors in bioethanol fermentation.
      Strains with different genetic backgrounds usually show diverse stress tolerance
      responses. An understanding of the mechanisms underlying these phenotypic
      diversities within S. cerevisiae populations could guide the construction of
      strains with desired traits. RESULTS: We explored the genetic characteristics of
      the bioethanol S. cerevisiae strain YJS329 and elucidated how genetic variations
      in its genome were correlated with specified traits compared to similar traits in
      the S288c-derived strain, BYZ1. Karyotypic electrophoresis combined with array
      comparative genomic hybridization indicated that YJS329 was a diploid strain with
      a relatively constant genome as a result of the fewer Ty elements and lack of
      structural polymorphisms between homologous chromosomes that it contained. By
      comparing the sequence with the S288c genome, a total of 64,998 SNPs, 7,093
      indels and 11 unique genes were identified in the genome of YJS329-derived
      haploid strain YJSH1 through whole-genome sequencing. Transcription comparison
      using RNA-Seq identified which of the differentially expressed genes were the
      main contributors to the phenotypic differences between YJS329 and BYZ1. By
      combining the results obtained from the genome sequences and the transcriptions,
      we predicted how the SNPs, indels and chromosomal copy number variations may
      affect the mRNA expression profiles and phenotypes of the yeast strains.
      Furthermore, some genetic breeding strategies to improve the adaptabilities of
      YJS329 were designed and experimentally verified. CONCLUSIONS: Through
      comparative functional genomic analysis, we have provided some insights into the
      mechanisms underlying the specific traits of the bioenthanol strain YJS329. The
      work reported here has not only enriched the available genetic resources of yeast
      but has also indicated how functional genomic studies can be used to improve
      genetic breeding in yeast.

PMID- 22978493
TI  - Guidelines on the laboratory aspects of assays used in haemostasis and
      thrombosis.

PMID- 22978492
TI  - Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent
      neurons following partial monoamine loss induced by methamphetamine.
AB  - The immediate-early gene Arc (activity-regulated cytoskeleton-associated protein)
      is provocative in the context of neuroplasticity because of its experience
      dependent regulation and mRNA transport to and translation at activated synapses.
      Normal rats have more preproenkephalin-negative (ppe-neg; presumed striatonigral)
      neurons with cytoplasmic Arc mRNA than ppe-positive (ppe-pos; striatopallidal)
      neurons, despite equivalent numbers of these neurons showing novelty-induced
      transcriptional activation of Arc. Furthermore, rats with partial monoamine loss
      induced by methamphetamine (METH) show impaired Arc mRNA expression in both ppe
      neg and ppe-pos neurons relative to normal animals following response-reversal
      learning. In this study, Arc expression induced by exposure to a novel
      environment was used to assess transcriptional activation and cytoplasmic
      localization of Arc mRNA in striatal efferent neuron subpopulations subsequent to
      METH-induced neurotoxicity. Partial monoamine depletion significantly altered Arc
      expression. Specifically, basal Arc expression was elevated, but novelty-induced
      transcriptional activation was abolished. Without novelty-induced Arc
      transcription, METH-pre-treated rats also had fewer neurons with cytoplasmic Arc
      mRNA expression, with the effect being greater for ppe-neg neurons. Thus, METH
      induced neurotoxicity substantially alters striatal efferent neuron function at
      the level of Arc transcription, suggesting a long-term shift in basal ganglia
      neuroplasticity processes subsequent to METH-induced neurotoxicity. Such changes
      potentially underlie striatally based learning deficits associated with METH
      induced neurotoxicity.

PMID- 22978494
TI  - Molecular tools to track bacteria responsible for fuel deterioration and
      microbiologically influenced corrosion.
AB  - Investigating the susceptibility of various fuels to anaerobic biodegradation has
      become complicated with the recognition that the fuels themselves are not
      sterile. Bacterial DNA could be obtained when various fuels were filtered through
      a hydrophobic teflon (0.22 MUm) membrane filter. Bacterial 16S rRNA genes from
      these preparations were PCR amplified, cloned, and the resulting libraries
      sequenced to identify the fuel-borne bacterial communities. The most common
      sequence, found in algal- and camelina-based biofuels as well as in ultra-low
      sulfur diesel (ULSD) and F76 diesel, was similar to that of a Tumebacillus. The
      next most common sequence was similar to Methylobacterium and was found in the
      biofuels and ULSD. Higher level phylogenetic groups included representatives of
      the Firmicutes (Bacillus, Lactobacillus and Streptococcus), several
      Actinobacteria, Deinococcus-Thermus, Chloroflexi, Cyanobacteria, Bacteroidetes,
      Alphaproteobacteria (Methylobacterium and Sphingomonadales), Betaproteobacteria
      (Oxalobacteraceae and Burkholderiales) and Deltaproteobacteria. All of the fuel
      associated bacterial sequences, except those obtained from a few facultative
      microorganisms, were from aerobes and only remotely affiliated with sequences
      that resulted from anaerobic successional events evident when ULSD was incubated
      with a coastal seawater and sediment inoculum. Thus, both traditional and
      alternate fuel formulations harbor a characteristic microflora, but these
      microorganisms contributed little to the successional patterns that ultimately
      resulted in fuel decomposition, sulfide formation and metal biocorrosion. The
      findings illustrate the value of molecular approaches to track the fate of
      bacteria that might come in contact with fuels and potentially contribute to
      corrosion problems throughout the energy value chain.

PMID- 22978495
TI  - Forkhead box(O) in control of reactive oxygen species and genomic stability to
      ensure healthy lifespan.
AB  - SIGNIFICANCE: Transcription factors of the Forkhead box O class (FOXOs) are
      associated with lifespan and play a role in age-related diseases. FOXOs,
      therefore, serve as a paradigm for developing an understanding as to how age
      related diseases, such as cancer and diabetes interconnect with lifespan.
      Understanding the regulatory inputs on FOXO may reveal how changes in these
      regulatory signaling pathways affect disease and lifespan. RECENT ADVANCES:
      Numerous regulators of FOXO have now been described and a clear and evolutionary
      conserved role has emerged for phosphoinositide-3 kinase/protein kinase B (also
      known as c-Akt or AKT) signaling and c-jun N-terminal kinase signaling. Analysis
      of FOXO function in the context of these signaling pathways has shown the
      importance of FOXO-mediated transcriptional regulation on cell cycle progression
      and other cell fates, such as cell metabolism, stress resistance, and apoptosis
      in mediating disease and lifespan. CRITICAL ISSUES: Persistent DNA damage is also
      tightly linked to disease and aging; yet, data on a possible link between DNA
      damage and FOXO have been limited. Here, we discuss possible connections between
      FOXO and the DNA damage response in the context of the broader role of connecting
      lifespan and disease. FUTURE DIRECTIONS: Understanding the role of lifespan in
      diseases onset may provide unique and generic possibilities to intervene in
      disease processes to ensure a healthy lifespan.

PMID- 22978496
TI  - Treatment of squamous cell carcinoma of the mobile tongue or tongue margins: an
      interdisciplinary challenge.
AB  - BACKGROUND: Standard treatment is surgery with stage dependent postoperative
      radio(chemo)therapy, however, for organ preservation preoperative
      radio(chemo)therapy is used as an individual approach. The present analysis was
      performed to access outcome and toxicity of radiotherapeutical treatment of
      squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Sixty-six patients
      (median age 55 years) with cancer of the mobile tongue (n=30) or tongue margins
      (n=36) treated between 1982 and 2006 were retrospectively analyzed. Treatment
      consisted of definitive- (n=13, median dose 66 Gy), adjuvant- (n=31, median dose
      60 Gy) or neoadjuvant radiotherapy (n=22, median dose 40 Gy) and chemotherapy
      (n=34) or immunotherapy (n=1). RESULTS: After a median follow-up of 29 months the
      three- and five-year overall survival (OS) rates were 59% and 46%, respectively.
      The median OS was 54 months. Forty-two patients achieved complete remission
      whereas 14 patients showed partial remission. The one- and two-year loco-regional
      progression-free survival (LRPFS) rates were 76% and 58%, respectively. The
      median LRPFS time was 36 months. In chi(2)-test, T-stage showed a trend towards
      impact on local recurrence (Pearson, p=0.082). In multivariate analysis, alcohol
      consumption (p=0.003) and gender (p=0.031) were prognostic. Grade III/IV acute
      toxicity was seen in 52% of patients. None of the locally controlled patients
      reported grade IV or higher late toxicity. CONCLUSION: No statistically
      significant differences between treatment modalities were found, but one should
      keep in mind that organ preservation plays a major role for quality of life. None
      of the locally controlled patients reported grade IV or higher late toxicity.
      However, tumor recurrence is common, especially in advanced tumor stage.
      Interdisciplinary concepts, further increasing the chance of tumor control are
      warranted.

PMID- 22978497
TI  - The fabric of thought: priming tactile properties during reading influences
      direct tactile perception.
AB  - The present studies examined whether implied tactile properties during language
      comprehension influence subsequent direct tactile perception, and the specificity
      of any such effects. Participants read sentences that implicitly conveyed
      information regarding tactile properties (e.g., Grace tried on a pair of thick
      corduroy pants while shopping) that were either related or unrelated to fabrics
      and varied in implied texture (smooth, medium, rough). After reading each
      sentence, participants then performed an unrelated rating task during which they
      felt and rated the texture of a presented fabric. Results demonstrated that the
      texture properties implied in sentences influence direct tactile perception.
      Specifically, after reading about a smooth or rough texture, subsequent fabric
      ratings became notably smoother or rougher, respectively. However, we also show
      that there was some specificity to these effects: Fabric-related sentences
      elicited more specific and interactive effects on subsequent ratings. Together,
      we demonstrate that under certain circumstances, language comprehension can prime
      tactile representations and affect direct tactile perception. Results are
      discussed with regard to the nature and scope of multimodal mental simulation
      during reading.

PMID- 22978498
TI  - Novel treatment strategy for Japanese newborns with high serum unbound bilirubin.
AB  - BACKGROUND: Serum unbound bilirubin (UB) is a measure of bilirubin not bound to
      albumin, and has been reported to be better than total bilirubin level at
      identifying infants at risk of developing bilirubin-induced neurotoxicity,
      including auditory abnormalities. A detailed treatment strategy for newborns with
      high serum UB has not been established. The aim of this study was to assess
      auditory outcomes in newborns with serum UB >=1.00 MUg/dL who were treated
      according to a novel treatment protocol. METHODS: A prospective clinical study
      was conducted in newborns weighing >1500 g with serum UB >=1.00 MUg/dL who were
      admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from
      2006 to 2011. Enrolled newborns were treated as follows: (i) if serum UB was 1.00
      1.50 MUg/dL, phototherapy and infusion were given with or without albumin or
      immunoglobulin therapy; and (ii) if serum UB was >1.50 MUg/dL, exchange
      transfusion was performed immediately. Auditory brainstem responses were
      evaluated at the time of discharge. RESULTS: A total of 89 Japanese newborns with
      UB >=1.00 MUg/dL were enrolled at a median age of 4 days. Of these, 85 had UB
      1.00-1.50 MUg/dL and four had UB >1.50 MUg/dL. After being treated according to
      the protocol, no newborns were diagnosed with auditory brainstem response
      abnormalities. CONCLUSIONS: The present treatment protocol for Japanese newborns
      with serum UB >=1.00 MUg/dL may be useful for the prevention of bilirubin-induced
      auditory abnormalities.

PMID- 22978499
TI  - Concerns and issues that have emerged with the evolution of evidence-based
      practice.

PMID- 22978500
TI  - Social support differentially moderates the impact of neuroticism and
      extraversion on mental wellbeing among community-dwelling older adults.
AB  - BACKGROUND: Personality affects psychological wellbeing, and social support
      networks may mediate this effect. This may be particularly pertinent in later
      life, when social structures change significantly, and can lead to a decline in
      psychological wellbeing. AIM: To examine, in an older population, whether the
      relationships between neuroticism and extraversion and mental wellbeing are
      moderated by available social support networks. METHOD: We gathered information
      from 536 community-dwelling older adults, regarding personality, social support
      networks, depressive symptomatology, anxiety and perceived stress, as well as
      controlling for age and gender. RESULTS: Neuroticism and extraversion interacted
      with social support networks to determine psychological wellbeing (depression,
      stress and anxiety). High scores on the social support networks measure appear to
      be protective against the deleterious effects of high scores on the neuroticism
      scale on psychological wellbeing. Meanwhile, individuals high in extraversion
      appear to require large social support networks in order to maintain
      psychological wellbeing. CONCLUSION: Large familial and friendship social support
      networks are associated with good psychological wellbeing. To optimise
      psychological wellbeing in older adults, improving social support networks may be
      differentially effective for different personality types.

PMID- 22978501
TI  - Suicidal ideation in adult offspring of depressed and matched control parents:
      childhood and concurrent predictors.
AB  - BACKGROUND: Suicidal ideation predicts suicide behaviors; however, research is
      needed on risk factors for suicidal ideation in adults, a common developmental
      period for first suicide attempts. AIMS: To examine childhood and concurrent
      predictors of suicidal ideation among 340 adult offspring of depressed and
      matched control parents. METHOD: Parents were assessed at baseline, and adult
      offspring were assessed 23 years later. RESULTS: Offspring who reported past
      month suicidal ideation (7%) had parents who, 23 years earlier, reported suicidal
      ideation, psychological inflexibility and use of avoidance coping. Offspring
      experiencing suicidal ideation were more likely to be unemployed and more
      depressed, consumed more alcohol and had more drinking problems. They were more
      anxious and inflexible, had weaker social ties and less cohesive families and had
      more negative life events and used more avoidance coping. A childhood risk index
      predicted offspring's suicidal ideation above and beyond concurrent factors.
      CONCLUSIONS: Along with concurrent risk factors, poor parental functioning may
      confer long-term risk for adult suicidal ideation. Interventions to prevent the
      transmission of suicidal ideation to offspring should focus on ameliorating
      parental risk factors.

PMID- 22978502
TI  - Partnering with mental health providers: a guide for services researchers.
AB  - BACKGROUND: There is a 20-year delay between the development of effective
      interventions for individuals with severe mental illness and widespread adoption
      in public mental health care settings. Academic-provider collaborations can
      shorten this gap, but establishing and maintaining partnerships entail
      significant challenges. AIMS: This paper identifies potential barriers to
      academic-provider research collaborations and provides guidelines to overcome
      these obstacles. METHOD: Authors from an academic institution and community
      mental health organization outline the components of their long-standing
      partnership, and discuss the lessons learned that were instrumental in
      establishing the collaborative model. Results Realistic resource allocation and
      training, a thorough understanding of the service model and consumer
      characteristics, systemic and bidirectional communication and concrete plans for
      post-project continuation are necessary at all project phases. CONCLUSIONS: A
      shared decision-making framework is essential for effective academic institution
      and community mental health agency collaborations and can facilitate long-term
      sustainability of novel interventions.

PMID- 22978503
TI  - A description and evaluation of a challenging behaviour workshop.
AB  - BACKGROUND: Ensuring good quality staff and patient relationships are key goals
      of long-stay inpatient services. It is therefore essential that staff have a good
      understanding of patients' needs and how to work with the challenges that can
      present in these environments. AIMS: We evaluated the feasibility and
      acceptability of a workshop to help psychiatric staff with challenging
      behaviours. DESIGN: We used a quasi experimental design with assessments carried
      out at baseline and post intervention. We provided the training to staff on one
      low secure psychiatric unit and recorded the uptake of outcome assessments and
      the workshop itself. We assessed staff-patient relationships, burnout and ward
      atmosphere and staff also completed satisfaction questionnaires. RESULTS: Sixty
      six percent of staff (n = 25) who were eligible to participate in the project
      completed initial outcome measures, but only 42% (n = 16) attended the workshop
      and only 34% (n = 13) completed follow-up measures. The workshop had no predicted
      effects on any of the outcomes assessed, but staff satisfaction with the training
      was generally positive. CONCLUSIONS: Building up positive relationships with
      staff, addressing negative expectations and seeking support from all levels of
      management are essential in terms of reducing barriers to training in psychiatric
      settings.

PMID- 22978504
TI  - Organised abuse: a neglected category of sexual abuse with significant lifetime
      mental healthcare sequelae.
AB  - BACKGROUND: Organised abuse (where multiple adults conspire to sexually abuse
      multiple children) has been one of the most controversial issues in debates over
      mental health practice with survivors of child sexual abuse. AIMS: The aim of
      this paper is to summarise and analyse the available prevalence data pertinent to
      organised abuse and to identify the challenges that organised abuse poses for
      mental health policy and practice. METHODS: Prevalence studies of sexual abuse
      based on community and clinical samples were reviewed for findings pertinent to
      organised abuse. Key indicators of organised abuse were selected and summarised
      on the basis of their association with the known characteristics of organised
      abuse. The literature regarding the health impacts of these indicators was also
      reviewed. RESULTS: A minority of people reporting contact sexual abuse in the
      community report experiences indicative of organised abuse. These indicators are
      elevated in particular settings and they are associated with poor mental and
      physical health. CONCLUSIONS: Organised abuse is rare but it is associated with
      poor mental and physical health outcomes. There is currently no source of
      integrated care for adults with histories of organised abuse. Many survivors end
      up in prison or homeless, chronically disabled by illness, or dead.

PMID- 22978508
TI  - The meaning and validation of social support networks for close family of persons
      with advanced cancer.
AB  - BACKGROUND: To strengthen the mental well-being of close family of persons newly
      diagnosed as having cancer, it is necessary to acquire a greater understanding of
      their experiences of social support networks, so as to better assess what
      resources are available to them from such networks and what professional measures
      are required. The main aim of the present study was to explore the meaning of
      these networks for close family of adult persons in the early stage of treatment
      for advanced lung or gastrointestinal cancer. An additional aim was to validate
      the study's empirical findings by means of the Finfgeld-Connett conceptual model
      for social support. The intention was to investigate whether these findings were
      in accordance with previous research in nursing. METHODS: Seventeen family
      members with a relative who 8-14 weeks earlier had been diagnosed as having lung
      or gastrointestinal cancer were interviewed. The data were subjected to
      qualitative latent content analysis and validated by means of identifying
      antecedents and critical attributes. RESULTS: The meaning or main attribute of
      the social support network was expressed by the theme Confirmation through
      togetherness, based on six subthemes covering emotional and, to a lesser extent,
      instrumental support. Confirmation through togetherness derived principally from
      information, understanding, encouragement, involvement and spiritual community.
      Three subthemes were identified as the antecedents to social support: Need of
      support, Desire for a deeper relationship with relatives, Network to turn to.
      Social support involves reciprocal exchange of verbal and non-verbal information
      provided mainly by lay persons. CONCLUSIONS: The study provides knowledge of the
      antecedents and attributes of social support networks, particularly from the
      perspective of close family of adult persons with advanced lung or
      gastrointestinal cancer. There is a need for measurement instruments that could
      encourage nurses and other health-care professionals to focus on family members'
      personal networks as a way to strengthen their mental health. There is also a
      need for further clarification of the meaning of social support versus caring
      during the whole illness trajectory of cancer from the family members'
      perspective.

PMID- 22978509
TI  - Convergence of genome-wide association and candidate gene studies for alcoholism.
AB  - BACKGROUND: Genome-wide association (GWA) studies have led to a paradigm shift in
      how researchers study the genetics underlying disease. Many GWA studies are now
      publicly available and can be used to examine whether or not previously proposed
      candidate genes are supported by GWA data. This approach is particularly
      important for the field of alcoholism because the contribution of many candidate
      genes remains controversial. METHODS: Using the Human Genome Epidemiology (HuGE)
      Navigator, we selected candidate genes for alcoholism that have been frequently
      examined in scientific articles in the past decade. Specific candidate loci as
      well as all the reported single nucleotide polymorphisms (SNPs) in candidate
      genes were examined in the Study of Addiction: Genetics and Environment (SAGE), a
      GWA study comparing alcohol-dependent and nondependent subjects. RESULTS: Several
      commonly reported candidate loci, including rs1800497 in DRD2, rs698 in ADH1C,
      rs1799971 in OPRM1, and rs4680 in COMT, are not replicated in SAGE (p > 0.05).
      Among candidate loci available for analysis, only rs279858 in GABRA2 (p = 0.0052,
      OR = 1.16) demonstrated a modest association. Examination of all SNPs reported in
      SAGE in over 50 candidate genes revealed no SNPs with large frequency differences
      between cases and controls, and the lowest p-value of any SNP was 0.0006.
      CONCLUSIONS: We provide evidence that several extensively studied candidate loci
      do not have a strong contribution to risk of developing alcohol dependence in
      European and African ancestry populations. Owing to the lack of coverage, we were
      unable to rule out the contribution of other variants, and these genes and
      particular loci warrant further investigation. Our analysis demonstrates that
      publicly available GWA results can be used to better understand which if any of
      previously proposed candidate genes contribute to disease. Furthermore, we
      illustrate how examining the convergence of candidate gene and GWA studies can
      help elucidate the genetic architecture of alcoholism and more generally complex
      diseases.

PMID- 22978510
TI  - Acute renal failure following oxalic acid poisoning: a case report.
AB  - Oxalic acid poisoning is being recognized as an emerging epidemic in the rural
      communities of Sri Lanka as it is a component of locally produced household
      laundry detergents. Herein we describe a case of a 32 year old female, presenting
      after direct ingestion of oxalic acid. She then went on to develop significant
      metabolic acidosis and acute renal failure, requiring dialysis. Renal biopsy
      revealed acute tubulointerstitial nephritis associated with diffuse moderate
      acute tubular damage with refractile crystals in some of the tubules. The patient
      symptomatically improved with haemodialysis and renal functions subsequently
      returned to normal.

PMID- 22978512
TI  - Toward understanding the redox properties of model chromophores from the green
      fluorescent protein family: an interplay between conjugation, resonance
      stabilization, and solvent effects.
AB  - The redox properties of model chromophores from the green fluorescent protein
      family are characterized computationally using density functional theory with a
      long-range corrected functional, the equation-of-motion coupled-cluster method,
      and implicit solvation models. The analysis of electron-donating abilities of the
      chromophores reveals an intricate interplay between the size of the chromophore,
      conjugation, resonance stabilization, presence of heteroatoms, and solvent
      effects. Our best estimates of the gas-phase vertical/adiabatic detachment
      energies of the deprotonated (i.e., anionic) model red, green, and blue
      chromophores are 3.27/3.15, 2.79/2.67, and 2.75/2.35 eV, respectively.
      Vertical/adiabatic ionization energies of the respective protonated (i.e.,
      neutral) species are 7.64/7.35, 7.38/7.15, and 7.70/7.32 eV, respectively. The
      standard reduction potentials (E(red)(0)) of the anionic (Chr*/Chr-) and neutral
      (Chr+*/Chr) model chromophores in acetonitrile are 0.34/1.40 V (red), 0.22/1.24 V
      (green), and -0.12/1.02 V (blue), suggesting, counterintuitively, that the red
      chromophore is more difficult to oxidize than the green and blue ones (in both
      neutral and deprotonated forms). The respective redox potentials in water follow
      a similar trend but are more positive than the acetonitrile values.

PMID- 22978511
TI  - Family history of alcohol dependence and antidepressant response to an N-methyl-D
      aspartate antagonist in bipolar depression.
AB  - OBJECTIVES: Both ketamine and ethanol are N-methyl-d-aspartate (NMDA) receptor
      antagonists. Ketamine has rapid antidepressant properties in major depressive
      disorder (MDD) as well as bipolar depression. In individuals with MDD, a positive
      family history of alcohol dependence (FHP) was associated with greater
      improvement in depressive symptoms after ketamine administration compared to
      individuals whose family history of alcohol dependence was negative (FHN). This
      study investigated whether FHP influences ketamine's antidepressant and
      perceptual effects in individuals with bipolar depression. METHODS: A post hoc
      analysis was conducted on 33 subjects with DSM-IV bipolar disorder (BD) type I or
      II depression pooled from two previously published studies. All subjects had
      undergone a double-blind, randomized, crossover trial of a single intravenous
      infusion of ketamine (0.5 mg/kg) combined with lithium or valproate therapy.
      Subjects were rated at baseline; at 40, 80, 120, and 230 min; and at days 1, 2,
      3, 7, 10, and 14 post-infusion. The primary outcome measure was Montgomery-Asberg
      Depression Rating Scale (MADRS) scores. Patients were categorized as FHP when
      they reported at least one first-degree relative with alcohol dependence.
      Measures of psychosis, dissociation, and dysphoria were also collected. RESULTS:
      After ketamine infusion, subjects with FHP showed significantly greater
      improvement on MADRS scores than FHN subjects. In addition, patients with FHP had
      attenuated psychotomimetic and dissociative scores compared to FHN patients.
      CONCLUSIONS: FHP appears to predict a more sustained antidepressant response to
      ketamine in individuals with BD. Family history of alcoholism may be an important
      consideration in the development of glutamatergic-based therapies for depression.

PMID- 22978513
TI  - A biphasic tumor consisting of pilocytic astrocytoma with an anaplastic solitary
      fibrous tumor component in the pineal region: a case report and literature
      review.
AB  - Here we report a case of a biphasic tumor consisting of pilocytic astrocytoma
      with anaplastic solitary fibrous tumor component in the pineal region. The
      majority of the tumor showed typical histologic features of pilocytic
      astrocytoma. A minor part of the tumor showed marked proliferation of short
      spindle cells around vessels. These spindle cells showed CD34 and CD99
      immunoreactivity. From a review of the literature, we found that only one similar
      case has been reported. Contrary to the reported case, our case showed anaplastic
      features of solitary fibrous tumor histology.

PMID- 22978515
TI  - Precise electrochemical control of ferromagnetism in a cyanide-bridged bimetallic
      coordination polymer.
AB  - Magnetic coordination polymers can exhibit controllable magnetism by introducing
      responsiveness to external stimuli. This report describes the precise control of
      magnetism of a cyanide-bridged bimetallic coordination polymer (Prussian blue
      analogue: PBA) through use of an electrochemical quantitative Li ion titration
      technique, i.e., the galvanostatic intermittent titration technique (GITT).
      K(0.2)Ni[Fe(CN)(6)](0.7).4.7H(2)O (NiFe-PBA) shows Li ion insertion/extraction
      reversibly accompanied with reversible Fe(3+)/Fe(2+) reduction/oxidation. When Li
      ion is inserted quantitatively into NiFe-PBA, the ferromagnetic transition
      temperature T(C) gradually decreases due to reduction of paramagnetic Fe(3+) to
      diamagnetic Fe(2+), and the ferromagnetic transition is completely suppressed for
      Li(0.6)(NiFe-PBA). On the other hand, T(C) increases continuously as Li ion is
      extracted due to oxidation of diamagnetic Fe(2+) to paramagnetic Fe(3+), and the
      ferromagnetic transition is nearly recovered for Li(0)(NiFe-PBA). Furthermore,
      the plots of T(C) as a function of the amount of inserted/extracted Li ion x are
      well consistent with the theoretical values calculated by the molecular-field
      approximation.

PMID- 22978514
TI  - Platelet-targeting sensor reveals thrombin gradients within blood clots forming
      in microfluidic assays and in mouse.
AB  - BACKGROUND: Thrombin undergoes convective and diffusive transport, making it
      difficult to visualize during thrombosis. We developed the first sensor capable
      of revealing inner clot thrombin dynamics. METHODS AND RESULTS: An N-terminal
      azido thrombin-sensitive fluorescent peptide (ThS-P) with a thrombin-releasable
      quencher was linked to anti-CD41 using click chemistry to generate a thrombin
      sensitive platelet binding sensor (ThS-Ab). Rapid thrombin cleavage of ThS-P
      (K(m) = 40.3 MUm, k(cat) = 1.5 s(-1) ) allowed thrombin monitoring by ThS-P or
      ThS-Ab in blood treated with 2-25 pm tissue factor (TF). Individual platelets had
      > 20-fold more ThS-Ab fluorescence after clotting. In a microfluidic assay of
      whole blood perfusion over collagen +/- linked TF (wall shear rate = 100 s(-1) ),
      ThS-Ab fluorescence increased between 90 and 450 s for 0.1-1 molecule-TF MUm(-2)
      and co-localized with platelets near fibrin. Without TF, neither thrombin nor
      fibrin was detected on the platelet deposits by 450 s. Using a microfluidic
      device to control the pressure drop across a thrombus forming on a porous
      collagen/TF plug (521 s(-1) ), thrombin and fibrin were detected at the thrombus
      collagen interface at a zero pressure drop, whereas 80% less thrombin was
      detected at 3200 Pa in concert with fibrin polymerizing within the collagen. With
      anti-mouse CD41 ThS-Ab deployed in a mouse laser injury model, the highest levels
      of thrombin arose between 40 and 160 s nearest the injury site where fibrin co
      localized and where the thrombus was most mechanically stable. CONCLUSION: ThS-Ab
      reveals thrombin locality, which depends on surface TF, flow and intrathrombus
      pressure gradients.

PMID- 22978516
TI  - Reply to "comment on 'condensation of excitons in a trap'".

PMID- 22978517
TI  - Antihistomonal effects of artemisinin and Artemisia annua extracts in vitro could
      not be confirmed by in vivo experiments in turkeys and chickens.
AB  - Five different Artemisia annua-derived materials (i.e. dry leaves, pure
      artemisinin, and hexane, dichloromethane or methanol extracts of leaves) were
      screened for their in vitro activities against six clonal cultures of Histomonas
      meleagridis. Except for the methanol extract, all tested materials displayed in
      vitro activity against all tested protozoal clones. Neither the dry plant
      material, extracts nor artemisinin showed any antibacterial activity against the
      xenic bacteria accompanying the six H. meleagridis clones at concentration levels
      identical to the antihistomonal setting. The dichloromethane extract of dry
      leaves (Ext-DCM) (minimal lethal concentration=1.0 mg/ml) and artemisinin (half
      maximal inhibitory concentration=1.295 mg/ml) had the most promising
      antihistomonal properties and were therefore subsequently tested in a
      standardized experimental infection model in both turkeys and chickens infected
      with clonal H. meleagridis. There were no differences between treatment groups,
      where all infected turkeys showed severe clinical histomonosis and demonstrated
      severe typhlohepatitis typical for histomonosis. Consistent with the infection
      model used, the infected chickens did not show any adverse clinical signs but
      contracted severe lesions in their caeca 7 and 10 days post infection (d.p.i.),
      liver lesions were absent to mild after 7 d.p.i. and progressed to severe lesions
      at 10 d.p.i.; thus no differences between treatment groups were observed. In
      conclusion, neither artemisinin nor Ext-DCM was able to prevent experimental
      histomonosis in turkeys and chickens at the given concentrations, which is
      contrary to the antihistomonal effect noticed in vitro even though the same
      clonal culture was used. The results of this study therefore clearly demonstrate
      the importance of defined in vivo experimentation in order to assess and verify
      in vitro results.

PMID- 22978518
TI  - Rise and fall of a wolf population: genetic diversity and structure during
      recovery, rapid expansion and drastic decline.
AB  - The grey wolves (Canis lupus) of Finland have had a varied history, with a period
      of rapid population expansion after the mid-1990s followed by a decline with a
      current census size of about 140 wolves. Here, we investigate the impact of
      unstable population size and connectivity on genetic diversity and structure in a
      long-term genetic study of 298 Finnish wolves born in 1995-2009 and genotyped for
      17 microsatellite loci. During the initial recovery and prior to population
      expansion, genetic diversity was high (1995-1997: LD-N(e)  = 67.2; H(o)  = 0.749;
      H(e)  = 0.709) despite a small census size and low number of breeders (N(c)  <
      100; N(b)  < 10) likely reflecting the status of the Russian source population.
      Surprisingly, observed heterozygosity decreased significantly during the study
      period (t = -2.643, P = 0.021) despite population expansion, likely a result of
      an increase in inbreeding (F(IS)  = 0.108 in 2007-2009) owing to a low degree of
      connectivity with adjacent Russian wolf population (m = 0.016-0.090; F(ST)  =
      0.086, P < 0.001) and population crash after 2006. However, population growth had
      a temporary positive impact on N(e)  and number of family lines. This study shows
      that even strong population growth alone might not be adequate to retain genetic
      diversity, especially when accompanied with low amount of subsequent gene flow
      and population decline.

PMID- 22978519
TI  - Assessing health and economic outcomes of interventions to reduce pregnancy
      related mortality in Nigeria.
AB  - BACKGROUND: Women in Nigeria face some of the highest maternal mortality risks in
      the world. We explore the benefits and cost-effectiveness of individual and
      integrated packages of interventions to prevent pregnancy-related deaths.
      METHODS: We adapt a previously validated maternal mortality model to Nigeria.
      Model outcomes included clinical events, population measures, costs, and cost
      effectiveness ratios. Separate models were adapted to Southwest and Northeast
      zones using survey-based data. Strategies consisted of improving coverage of
      effective interventions, and could include improved logistics. RESULTS:
      Increasing family planning was the most effective individual intervention to
      reduce pregnancy-related mortality, was cost saving in the Southwest zone and
      cost-effective elsewhere, and prevented nearly 1 in 5 abortion-related deaths.
      However, with a singular focus on family planning and safe abortion, mortality
      reduction would plateau below MDG 5. Strategies that could prevent 4 out of 5
      maternal deaths included an integrated and stepwise approach that includes
      increased skilled deliveries, facility births, access to antenatal/postpartum
      care, improved recognition of referral need, transport, and availability quality
      of EmOC in addition to family planning and safe abortion. The economic benefits
      of these strategies ranged from being cost-saving to having incremental cost
      effectiveness ratios less than $500 per YLS, well below Nigeria's per capita GDP.
      CONCLUSIONS: Early intensive efforts to improve family planning and control of
      fertility choices, accompanied by a stepwise effort to scale-up capacity for
      integrated maternal health services over several years, will save lives and
      provide equal or greater value than many public health interventions we consider
      among the most cost-effective (e.g., childhood immunization).

PMID- 22978520
TI  - Mono- and dithiol glutaredoxins in the trypanothione-based redox metabolism of
      pathogenic trypanosomes.
AB  - SIGNIFICANCE: Glutaredoxins are ubiquitous small thiol proteins of the
      thioredoxin-fold superfamily. Two major groups are distinguished based on their
      active sites: the dithiol (2-C-Grxs) and the monothiol (1-C-Grxs) glutaredoxins
      with a CXXC and a CXXS active site motif, respectively. Glutaredoxins are
      involved in cellular redox and/or iron sulfur metabolism. Usually their functions
      are closely linked to the glutathione system. Trypanosomatids, the causative
      agents of several tropical diseases, rely on trypanothione as principal low
      molecular mass thiol, and their glutaredoxins readily react with the unique
      bis(glutathionyl) spermidine conjugate. RECENT ADVANCES: Two 2-C-Grxs and three 1
      C-Grxs have been identified in pathogenic trypanosomatids. The 2-C-Grxs catalyze
      the reduction of glutathione disulfide by trypanothione and display reductase
      activity towards protein disulfides, as well as protein-glutathione mixed
      disulfides. In vitro, all three 1-C-Grxs as well as the cytosolic 2-C-Grx of
      Trypanosoma brucei can complex an iron-sulfur cluster. Recently the structure of
      the 1-C-Grx1 has been solved by NMR spectroscopy. The structure is very similar
      to those of other 1-C-Grxs, with some differences in the loop containing the
      conserved cis-Pro and the surface charge distribution. CRITICAL ISSUES: Although
      four of the five trypanosomal glutaredoxins proved to coordinate an iron-sulfur
      cluster in vitro, the physiological role of the mitochondrial and cytosolic
      proteins, respectively, has only started to be unraveled. FUTURE DIRECTIONS: The
      use of trypanothione by the glutaredoxins has established a novel role for this
      parasite-specific dithiol. Future work should reveal if these differences can be
      exploited for the development of novel antiparasitic drugs.

PMID- 22978521
TI  - Genome-wide association between DNA methylation and alternative splicing in an
      invertebrate.
AB  - BACKGROUND: Gene bodies are the most evolutionarily conserved targets of DNA
      methylation in eukaryotes. However, the regulatory functions of gene body DNA
      methylation remain largely unknown. DNA methylation in insects appears to be
      primarily confined to exons. Two recent studies in Apis mellifera (honeybee) and
      Nasonia vitripennis (jewel wasp) analyzed transcription and DNA methylation data
      for one gene in each species to demonstrate that exon-specific DNA methylation
      may be associated with alternative splicing events. In this study we investigated
      the relationship between DNA methylation, alternative splicing, and cross-species
      gene conservation on a genome-wide scale using genome-wide transcription and DNA
      methylation data. RESULTS: We generated RNA deep sequencing data (RNA-seq) to
      measure genome-wide mRNA expression at the exon- and gene-level. We produced a de
      novo transcriptome from this RNA-seq data and computationally predicted splice
      variants for the honeybee genome. We found that exons that are included in
      transcription are higher methylated than exons that are skipped during
      transcription. We detected enrichment for alternative splicing among methylated
      genes compared to unmethylated genes using fisher's exact test. We performed a
      statistical analysis to reveal that the presence of DNA methylation or
      alternative splicing are both factors associated with a longer gene length and a
      greater number of exons in genes. In concordance with this observation, a
      conservation analysis using BLAST revealed that each of these factors is also
      associated with higher cross-species gene conservation. CONCLUSIONS: This study
      constitutes the first genome-wide analysis exhibiting a positive relationship
      between exon-level DNA methylation and mRNA expression in the honeybee. Our
      finding that methylated genes are enriched for alternative splicing suggests
      that, in invertebrates, exon-level DNA methylation may play a role in the
      construction of splice variants by positively influencing exon inclusion during
      transcription. The results from our cross-species homology analysis suggest that
      DNA methylation and alternative splicing are genetic mechanisms whose utilization
      could contribute to a longer gene length and a slower rate of gene evolution.

PMID- 22978522
TI  - Lupus anticoagulant detection: out of control?
AB  - INTRODUCTION: Expert guidelines indicate that normalised ratios are preferred to
      clotting times for lupus anticoagulant (LA) assays to mitigate analytical
      variation. We investigated the effects of deriving normalised ratios from the
      reference interval (RI) mean or different normal pooled plasmas (NPP). METHODS:
      Screen, confirm and mixing tests for dilute Russell's viper venom time and APTT
      were converted to normalised ratios and interpreted for LA. RESULTS: Of 1000
      clinical samples, 824 generated identical interpretations using RI mean or NPP
      derived ratios and 57 identified LAs in one or both assays via either
      denominator. Separate RIs were applied for normalised ratios derived from the NPP
      or RI mean. Applying percentage correction index (PCI) to screen and confirm
      assays irrespective of screen elevation increased agreement to 92.5%. Two frozen
      and one lyophilised NPP were then used to derive ratios for 204 samples and 130
      generated identical interpretations with all NPPs, 14 had overall interpretation
      parity and 19 overall agreement via PCI, giving 79.9% overall agreement. The
      results derived from each NPP were interpreted against RIs derived from RI means
      to reflect differences resulting from NPPs with clotting times dissimilar to RI
      means. CONCLUSIONS: Disparities were largely a function of closeness of NPP
      clotting times to test RI means and not owing to clotting factor level
      differences and likely related to manufacturing variables. Diagnostic benefit of
      normalised ratios can be maximised by matching NPP values to RI means. If RI mean
      is employed, and it likely requires re-establishing with new reagent batches.

PMID- 22978523
TI  - Evisceration and enucleation: a national survey of practice patterns in the
      United States.
AB  - BACKGROUND AND OBJECTIVE: The management of evisceration and enucleation has
      changed over time. The authors assessed the practice patterns regarding eye
      removal among oculoplastic surgeons. PATIENTS AND METHODS: Internet-based surveys
      were sent to American Society of Ophthalmic Plastic and Reconstructive Surgeons
      members regarding preferences in evisceration and/or enucleation, including
      indications, surgical techniques, preoperative evaluation modalities, implant
      types used, and postoperative complications experienced. RESULTS: Surgeons who
      recently completed fellowship training are more likely to perform eviscerations
      than their senior counterparts. The variety of viable implant types and the use
      of enucleation or evisceration for certain indications were not always in
      concordance with historical guiding principles. However, changing trends are in
      line with the current literature. CONCLUSION: Current practice patterns reflect
      recent literature and historical trends.

PMID- 22978524
TI  - Role of the blood-cerebrospinal fluid barrier transporter as a cerebral clearance
      system for prostaglandin E2 produced in the brain.
AB  - An increasing level of prostaglandin (PG) E(2)  is involved in the progression of
      neuroinflammation induced by ischemia and bacterial infection. Although an
      imbalance in the rates of production and clearance of PGE(2)  under these
      pathological conditions appears to affect the concentration of PGE(2)  in the
      cerebrospinal fluid (CSF), the regulatory system remains incompletely understood.
      The purpose of this study was to investigate the cellular system of PGE(2) 
      production via microsomal PGE synthetase-1 (mPGES-1), the inducible PGE(2) 
      generating enzyme, and PGE(2)  elimination from the CSF via the blood-CSF barrier
      (BCSFB). Immunohistochemical analysis revealed that mPGES-1 was expressed in the
      soma and perivascular sheets of astrocytes, pia mater, and brain blood vessel
      endothelial cells, suggesting that these cells are local production sites of
      PGE(2)  in the CSF. The in vivo PGE(2)  elimination clearance from the CSF was
      eightfold greater than that of d-mannitol, which is considered to reflect CSF
      bulk flow. This process was inhibited by the simultaneous injection of unlabeled
      PGE(2)  and beta-lactam antibiotics, such as benzylpenicillin, cefazolin, and
      ceftriaxone, which are substrates and/or inhibitors of organic anion transporter
      3 (OAT3). The characteristics of PGE(2)  uptake by the isolated choroid plexus
      were at least partially consistent with those of OAT3. OAT3 was able to mediate
      PGE(2)  transport with a Michaelis-Menten constant of 4.24 MUM. These findings
      indicate that a system regulating the PGE(2)  level in the CSF involves OAT3
      mediated PGE(2)  uptake by choroid plexus epithelial cells, acting as a cerebral
      clearance pathway via the BCSFB of locally produced PGE(2) .

PMID- 22978525
TI  - A novel compound, denosomin, ameliorates spinal cord injury via axonal growth
      associated with astrocyte-secreted vimentin.
AB  - BACKGROUND AND PURPOSE: In the spinal cord injury (SCI) axon regeneration is
      inhibited by the glial scar, which contains reactive astrocytes that secrete
      inhibitory chondroitin sulphate proteoglycan (CSPG). We previously reported that
      a novel compound, denosomin, promotes axonal growth under degenerative conditions
      in cultured cortical neurons. In this study, we investigated the effects of
      denosomin on functional recovery in SCI mice and elucidated the mechanism though
      which denosomin induces axonal growth in the injured spinal cord. EXPERIMENTAL
      APPROACH: Denosomin was administered p.o. for 7 or 14 days to contusion mice.
      Behavioural evaluations and immunohistochemistry were done. Primary cultured
      cortical neurons and astrocytes were treated with denosomin to investigate the
      mechanism of axonal growth facilitation. KEY RESULTS: Denosomin improved hind
      limb motor dysfunction and axonal growth, especially in the 5-HT-positive tracts
      across the scar and increased the density of astrocytes. Denosomin increased
      astrocyte proliferation, inhibited astrocytic death and increased the expression
      and secretion of vimentin in cultured astrocytes. Furthermore, vimentin increased
      axonal outgrowth in cultured neurons, even in the presence of inhibitory CSPG.
      Denosomin increased the number of vimentin-expressing astrocytes inside glial
      scars of SCI mice, and 5-HT-positive axonal growth occurred in a vimentin
      associated manner. CONCLUSION AND IMPLICATIONS: Denosomin increased the ratio of
      astrocytes that secrete vimentin as an axonal growth facilitator, which, we
      propose enhances axonal growth beyond the glial scar and promotes functional
      recovery in SCI mice. This study is the first to demonstrate this novel role of
      vimentin in SCI and drug-mediated modification of the inhibitory property of
      reactive astrocytes.

PMID- 22978526
TI  - Cataract surgery among Medicare beneficiaries.
AB  - PURPOSE: To present descriptive epidemiology of cataract surgery among Medicare
      recipients in the United States. SETTING: Cataract surgery performed on Medicare
      beneficiaries in 2003 and 2004. METHODS: Medicare claims data were used to
      identify all cataract surgery claims for procedures performed in the United
      States in 2003-2004. Standard assumptions were used to limit the claims to actual
      cataract surgery procedures performed. Summary statistics were created to
      determine the number of procedures performed for each outcome of interest:
      cataract surgery rates by age, sex, race and state; surgical volume by facility
      type and surgeon characteristics; time interval between first- and second-eye
      cataract surgery. RESULTS: The national cataract surgery rate for 2003-2004 was
      61.8 per 1000 Medicare beneficiary person-years. The rate was significantly
      higher for females and for those aged 75-84 years. After adjustment for age and
      sex, blacks had approximately a 30% lower rate of surgery than whites. While only
      5% of cataract surgeons performed more than 500 cataract surgeries annually,
      these surgeons performed 26% of the total cataract surgeries. Increasing surgical
      volume was found to be highly correlated with use of ambulatory surgical centers
      and reduced time interval between first- and second-eye surgery in the same
      patient. CONCLUSIONS: The epidemiology of cataract surgery in the United States
      Medicare population documents substantial variation in surgical rates by race,
      sex, age, and by certain provider characteristics.

PMID- 22978527
TI  - Willingness to pay for cataract surgery in post-operative cataract patients in
      rural Malawi.
AB  - BACKGROUND: In order to improve the sustainability of eye care programs including
      provision of surgical services, an understanding of a patient's capacity to
      contribute towards the costs relating to sight-restoring surgery is essential.
      Therefore, we investigated willingness to pay for cataract surgery in a hospital
      based cross-sectional study in rural Malawi. METHODS: We interviewed consecutive
      patients following surgery for senile cataract at Nkhoma Eye Hospital, Malawi.
      Patients were asked about their willingness to pay for surgery (in local
      currency, Kwacha, as well as surrogates for money). We also collected data on
      socio-demographic variables and pre- and post-operative visual acuity (VA).
      RESULTS: A total of 212 participants were included (99.5% acceptance), of whom
      82.0% were farmers. Mean age of participants was 68.2 years, and 89 (42.0%) were
      female. There were 136 (64.2%) who were willing to pay something. Median
      willingness to pay was 500 Kwacha (interquartile range 0-2,000; ~US$3.00, August
      2011). Following adjustment for age, sex, family size and occupation, patients
      who were blind pre-operatively (pinhole-corrected VA<3/60) were less likely to
      pay something for surgery (odds ratio 0.44, 95% confidence interval 0.20-0.96, P
      = 0.038) compared to those with VA>6/60. CONCLUSION: In this setting where people
      are used to free services, the median monetary amount elderly patients were
      willing to pay for surgery is well below the actual cost of screening, transport,
      accommodation and surgery. Substantial cost recovery will require pre-operative
      involvement of family members, but might slow down current screening practices
      and also lower acceptance rates.

PMID- 22978528
TI  - Intraocular pressure and its relationship to ocular and systemic factors in a
      healthy Chinese rural population: the Handan Eye Study.
AB  - PURPOSE: To describe the distribution of and factors related to intraocular
      pressure (IOP) in a healthy adult rural Chinese population in northern China.
      METHODS: The Handan Eye Study is a cross-sectional, population-based study of eye
      diseases among 6,830 (90.4% response rate) rural Chinese persons aged 30+ years.
      Participants underwent an interviewer-administered questionnaire and a complete
      ocular examination, including standardized measurement of IOP with Perkins
      applanation tonometry. RESULTS: After excluding persons with glaucoma, or those
      with diseases that have a marked effect on IOP or that preclude accurate IOP
      measurement, 6,101 persons were included in the current analysis. Mean IOP (mean
      +/- standard deviation) of the study population was 15.0 +/- 2.8 mmHg. Men had
      lower IOP than women (14.6 +/- 2.8 mmHg versus 15.4 +/- 2.7 mmHg, t = -8.37, P <
      0.001). In the multivariate analysis younger age, female sex, presence of
      diabetes mellitus, higher blood pressure, higher body mass index, thicker central
      cornea and higher myopia were associated with higher IOP. CONCLUSIONS: Mean IOP
      among persons living in rural northern China was similar to that recently
      reported in southern China. IOP appeared to be lower with increasing age in
      Chinese subjects, which contrasts with results in white populations.

PMID- 22978530
TI  - Does training clinic nurses to test pinhole visual acuity as a screen for
      glaucoma increase glaucoma referrals to eye care professionals? A pilot study in
      Malawi.
AB  - PURPOSE: To test whether general nurses, trained in screening for glaucoma, can
      increase the number of glaucoma cases seen by eye-care professionals in a rural
      setting in Africa. METHODS: In two districts in Malawi, 87 clinic nurses and two
      ophthalmic clinical officers were trained in case detection and referral of
      patients with suspect glaucoma. Data were collected on the number of patients
      screened and referred over a 12-month period. The clinic nurses and ophthalmic
      clinical officers received supportive supervision four times during the period
      and interviews were used to elicit their perspectives on the training and
      referral procedures. RESULTS: The 87 nurses screened 294 people (mean 3.4 per
      nurse) and referred 147 (50%) of them. Of the 147 referred, 56 (38%) were seen by
      the ophthalmic clinical officers who referred 15 (27%) to the ophthalmologist.
      Only two people were seen by the ophthalmologist. Testing visual acuity in people
      over 40 years of age was not seen as a priority by primary level clinic nurses.
      Nurses reported that cost and distance were barriers precluding attendance by
      patients at the next level. Women were two times less likely to be referred.
      About one quarter of patients who were offered surgery refused. Fewer than half
      the patients who had surgery attend for follow-up. CONCLUSIONS: Training general
      nurses to screen for and refer suspect glaucoma cases did not lead to increased
      glaucoma service delivery. Other strategies to identify high risk patients need
      to be tested.

PMID- 22978529
TI  - Glaucoma, Alzheimer disease and other dementia: a longitudinal analysis.
AB  - PURPOSE: To evaluate the risk of developing Alzheimer disease (AD) or other
      dementia in patients diagnosed with open-angle glaucoma (OAG) in a nationally
      representative longitudinal sample of elderly persons. METHODS: This
      retrospective cohort study (January 1, 1994-December 31, 2007) used Medicare 5%
      claims data. We identified beneficiaries aged 68+ years who had at least two
      claims with diagnoses of OAG and no Alzheimer or other dementia in 1994, using a
      3-year look-back period between 1991 and 1993 (n = 63,235) and beneficiaries
      matched on age, sex, race, and Charlson index without a diagnosis of OAG
      throughout the observational period (n = 63,235), using propensity score
      matching. Using a Cox Proportional Hazards model, we analyzed time to AD
      diagnosis and time to AD or other dementia diagnosis. RESULTS: Elderly
      individuals diagnosed with OAG did not have an increased rate of AD and other
      dementia diagnosis compared to those without OAG during a 14-year follow-up
      period, even after controlling for relevant covariates present at baseline.
      CONCLUSIONS: Individuals aged 68+ years diagnosed with OAG have a decreased rate
      of AD or other dementia diagnosis compared to control patients without an OAG
      diagnosis. Although OAG and AD are both age-related neurodegenerative diseases,
      our findings do not support a positive association.

PMID- 22978531
TI  - Prevalence of neurological involvement and malformative/systemic syndromes in A-
      and V-pattern strabismus.
AB  - PURPOSE: To evaluate the prevalence of neurological involvement and
      malformative/systemic syndromes in A- and V-patterns with respect to other kinds
      of infantile concomitant strabismus. METHODS: A retrospective comparative study
      of 14,006 consecutive patients examined in the Pediatric Ophthalmology and
      Strabismus Unit at the Catholic University of Rome between January 2002 and
      February 2010 was carried out. A total of 2.72% (385) of patients presented with
      concomitant constant infantile strabismus associated with A- and V- patterns
      (study group; mean age 8 years; range: 8 months - 37 years; male 211, female
      174). Another 377 consecutive patients affected by infantile concomitant
      strabismus without A- or V- patterns were used as controls (control group; mean
      age 9 years, range: 1-34 years; male 194, female 183). All patients underwent a
      complete ophthalmologic and orthoptic examination with ocular motility evaluation
      and prism cover test or the Hirschberg test in primary, up and down gaze
      positions, as well as cycloplegic retinoscopy. The angle of deviation was
      evaluated at near (33 cm) and distance fixation (6 m) with full correction of
      refraction. RESULTS: Neurological involvement and malformative/systemic syndromes
      were observed in 30.4% of the study group and in 19.8% of patients in the control
      group (P < 0.001). Patients with A-pattern showed a greater prevalence of
      neurological impairment, hydrocephalus and meningomyelocele, while those affected
      by V-pattern exhibited a greater prevalence of craniosynostosis and malformative
      syndromes. CONCLUSIONS: Neurological involvement and malformative/systemic
      syndromes seem to be more evident in patients presenting with A- and V-pattern
      strabismus.

PMID- 22978532
TI  - Andhra Pradesh Eye Disease Study - Visual Function Questionnaire: further
      improvements in psychometric properties using Rasch analysis.
AB  - PURPOSE: Previous Rasch analysis of the Andhra Pradesh Eye Disease Study-Visual
      Function Questionnaire (APEDS-VFQ) lacked comprehensiveness, specifically,
      dimensionality (whether it measures single/multiple constructs). Therefore, using
      the Rasch model this study provides a detailed assessment of psychometric
      properties of the APEDS-VFQ. METHODS: A total of 351 visually impaired adults
      (mean age, 43.3 years) were verbally administered the APEDS-VFQ. Rasch analysis
      was used to assess the psychometric properties of the instrument. RESULTS:
      Participants could distinguish only three categories of difficulty, so response
      categories were reduced from five to three. A single item ("reading small prints
      in newspaper/magazines", infit mean square 1.54) misfit the model. The overall
      pattern of fit statistics for item and person measures suggested that the
      underlying construct (visual ability) is not unidimensional. When the items were
      grouped into subsets based on functional requirements (resolution, contrast
      sensitivity, illumination and peripheral vision) and separate person measures
      were estimated for each of these domains, the first principal component contained
      the visual ability and accounted for 72% of the variance. Item measure
      distributions could be divided into 18 strata, and item-separation reliability
      was 0.99. Person measures could be divided into three statistically distinct
      strata and the person-separation reliability was 0.81. CONCLUSIONS: The APEDS-VFQ
      is a precise measure of visual ability in visually impaired adults in India.
      Similar to other visual function questionnaires developed for the Western
      population, our results demonstrate that visual ability is a two-factor composite
      latent variable; one dimension heavily influences reading and the other most
      heavily influences peripheral vision (mobility).

PMID- 22978533
TI  - Correlation and reproducibility of retinal vascular geometric measurements for
      stereoscopic retinal images of the same eyes.
AB  - PURPOSE: To assess the correlation and reproducibility of retinal vascular
      geometric measurements obtained from two stereo-paired fundus images. METHODS:
      Thirty stereoscopic pairs of color optic disc-centered photographs from the Blue
      Mountains Eye Study were analyzed. Side-by-side grading was performed by a single
      grader, using semi-automated computer software to quantify the following retinal
      geometric parameters: (1) retinal arteriolar/venular caliber (CRAE/CRVE); (2)
      arteriole-to-venule ratio (AVR); (3) branching angle; and (4) tortuosity. We used
      Pearson correlation (r), intra-class correlation coefficient (ICC), and Bland
      Altman plots to assess within-pair correlation and reproducibility for each
      parameter measured. RESULTS: Inter- and intra-grader r and ICC were high (all r >
      0.90 and ICC > 0.90), except for branching angle (ICCs between 0.69-0.83). There
      was no significant difference between within-pair means of all retinal vascular
      geometric parameters, before and after excluding poor quality images. CRAE, CRVE,
      AVR, and arteriolar and venular tortuosity showed very high within-pair
      correlation and agreement (all r > 0.80 and all ICC > 0.90 respectively).
      Arteriolar and venular branching angles demonstrated moderate within-pair
      correlation (r = 0.65 and r = 0.62, respectively) and within-pair agreement (ICC
      = 0.76 and ICC = 0.77, respectively). CONCLUSIONS: Use of computer-assisted
      software to measure retinal vascular geometric parameters from paired fundus
      images was highly repeatable and is robust to differences in photographic angles
      of paired stereo images. Such measurements can be applied to evaluate temporal
      changes in longitudinal studies.

PMID- 22978534
TI  - Low accuracy of endoscopic ultrasonography for detailed T staging in gastric
      cancer.
AB  - BACKGROUND: The accuracy of endoscopic ultrasonography (EUS) for preoperative
      staging of gastric cancer varies. The aim of this study was to investigate the
      accuracy of EUS tumor (T) and node (N) staging, and to identify the
      histopathological factors influencing accuracy based on the detailed tumor depth
      of gastric cancer. METHODS: In total, 309 patients with gastric cancer with
      confirmed pathological staging underwent EUS examination for preoperative staging
      at Seoul St. Mary's Hospital, Korea, between January and December 2009. The T and
      N staging of EUS and the pathologic report were compared. RESULTS: The overall
      accuracies of EUS for T stage and the detailed T stages were 70.2% and 43.0%,
      respectively. In detailed stage, tumors greater than 50 mm in diameter were
      significantly associated with T overstaging (odds ratio (OR) = 2.094). The
      overall accuracy of EUS for N staging was 71.2%. Tumor size (20 mm <= size < 50
      mm, OR = 4.389; and 50 mm <= size, OR = 8.170), cross-sectional tumor location
      (circumferential, OR = 4.381) and tumor depth (submucosa, OR = 3.324; muscular
      propria, OR = 6.923; sub-serosa, OR = 4.517; and serosa-exposed, OR = 6.495) were
      significant factors affecting incorrect nodal detection. CONCLUSIONS: Careful
      attention is required during EUS examination of large-sized gastric cancers to
      increase accuracy, especially for T staging.

PMID- 22978535
TI  - Respiratory viruses in neonates hospitalized with acute lower respiratory tract
      infections.
AB  - BACKGROUND: The burden of respiratory syncytial virus (RSV) in neonates has not
      been clearly studied. The aims of this study were to determine the overall
      distribution of respiratory viruses in neonates hospitalized with acute lower
      respiratory tract infectiosns (ALRI) and to describe the clinical characteristics
      of RSV infections in these neonates. METHODS: From January 2009 through May 2010,
      neonates aged <1 month who were hospitalized with ALRI and did not have
      underlying disease were included in the study. Viruses were identified on
      multiplex reverse transcription polymerase chain reaction using nasal swab
      samples. Clinical variables were evaluated between the RSV and non-RSV infection
      groups. RESULTS: Of the 108 infants included in the study, 46 (42.6%) had RSV;
      human rhinovirus (18.5%), human parainfluenza virus 3 (7.5%), and human
      metapneumovirus (3.7%) were the next most common infections. Codetections
      accounted for 8.3% of the cases. Crowding increased the risk of RSV infection
      compared to the non-RSV group (OR, 16.5; P = 0.001). The RSV group had a greater
      incidence of dyspnea (P = 0.027), pneumonia (P < 0.001), requirement for oxygen
      (P < 0.001), and prolonged hospitalization (P = 0.011) than the non-RSV group.
      CONCLUSIONS: RSV was the most common viral etiology in neonates without
      underlying diseases who were hospitalized with ALRI. The disease severity of RSV
      infection was worse than that of other detected viral infections. Strict
      prevention strategies should be considered in overcrowded situations.

PMID- 22978536
TI  - Putative paired small multidrug resistance family proteins PsmrAB, the homolog of
      YvdSR, actually function as a novel two-component Na(+)/H(+) antiporter.
AB  - In this study, metagenomic DNA was screened for the Na(+)/H(+) antiporter gene
      from the halophilic bacteria from Daban Salt Lake using Escherichia coli KNabc
      lacking three major Na(+)/H(+) antiporters, and two genes psmrAB predicted to
      encode paired small multidrug resistance (PSMR) family proteins, the homolog of
      YvdSR, were finally cloned. Only the simultaneous presence of psmrAB, but not the
      single gene alone, conferred the tolerance of E. coli KNabc to up to 0.6 M NaCl
      and at alkaline pH. pH-dependent Na(+)(Li(+))/H(+) antiport activity was detected
      from everted membrane vesicles prepared from E. coli KNabc cells carrying psmrAB,
      which had the highest activity at pH 9.0. However, a detailed test for
      antimicrobial drugs showed that E. coli DH5alpha with psmrAB only exhibited
      slight resistance to chloramphenicol, but not other representative antimicrobial
      drugs especially ethidium bromide. Protein sequence alignment showed that neither
      PsmrA nor PsmrB has homology with known single-gene or multiple-gene Na(+)/H(+)
      antiporters, or such proteins as TetA(L) and MdfA with Na(+)/H(+) antiport
      activity. Taken together, PsmrAB should function mainly as a novel two-component
      Na(+)/H(+) antiporter. This is the first example of a PSMR family member that
      exhibits Na(+)/H(+) antiporter activity.

PMID- 22978537
TI  - Extent of resection in patients with glioblastoma: limiting factors, perception
      of resectability, and effect on survival.
AB  - OBJECT: The extent of resection (EOR) is a known prognostic factor in patients
      with glioblastoma. However, gross-total resection (GTR) is not always achieved.
      Understanding the factors that prevent GTR is helpful in surgical planning and
      when counseling patients. The goal of this study was to identify demographic,
      tumor-related, and technical factors that influence EOR and to define the
      relationship between the surgeon's impression of EOR and radiographically
      determined EOR. METHODS: The authors performed a retrospective review of the
      electronic medical records to identify all patients who underwent craniotomy for
      glioblastoma resection between 2006 and 2009 and who had both preoperative and
      postoperative MRI studies. Forty-six patients were identified and were included
      in the study. Image analysis software (FIJI) was used to perform volumetric
      analysis of tumor size and EOR based on preoperative and postoperative MRI. Using
      multivariate analysis, the authors assessed factors associated with EOR and
      residual tumor volume. Perception of resectability was described using bivariate
      statistics, and survival was described using the log-rank test and Kaplan-Meier
      curves. RESULTS: The EOR was less for tumors in eloquent areas (p = 0.014) and
      those touching ventricles (p = 0.031). Left parietal tumors had significantly
      greater residual volume (p = 0.042). The average EOR was 91.0% in this series.
      There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which
      GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be
      safely achieved in 37.0% of patients (17 of 46) in this series. Among patients
      with safely resectable tumors, radiographically complete resection was achieved
      in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a
      significantly greater 1-year survival (76.5%) than an EOR less than 90% (p =
      0.005). CONCLUSIONS: The authors' findings confirm that tumor location affects
      EOR and suggest that EOR may also be influenced by the surgeon's ability to judge
      the presence of residual tumor during surgery. The surgeon's ability to judge
      completeness of resection during surgery is commonly inaccurate. The authors'
      study confirms the impact of EOR on 1-year survival.

PMID- 22978538
TI  - Repair of a median nerve transection injury using multiple nerve transfers, with
      long-term functional recovery.
AB  - Complete loss of median nerve motor function is a rare but devastating injury.
      Loss of median motor hand function and upper-extremity pronation can
      significantly impact a patient's ability to perform many activities of daily
      living independently. The authors report the long-term follow-up in a case of
      median nerve motor fiber transection that occurred during an arthroscopic elbow
      procedure, which was then treated with multiple nerve transfers. Motor
      reconstruction used the nerves to the supinator and extensor carpi radialis
      brevis to transfer to the anterior interosseous nerve and pronator. Sensory
      sensation was restored using the lateral antebrachial cutaneous (LABC) nerve to
      transfer to a portion of the sensory component of the median nerve, and a second
      cable of LABC nerve as a direct median nerve sensory graft. The patient
      ultimately recovered near normal motor function of the median nerve, but had
      persistent pain symptoms 4 years postinjury.

PMID- 22978539
TI  - Hybrid peripheral nerve sheath tumor.
AB  - In recent literature, there have been case reports of an extremely rare entity
      characterized by hybrid peripheral nerve tumors consisting of elements of
      neurofibroma, schwannoma, and/or perineurioma. The authors present a unique case
      of a patient with multiple painful hybrid tumors with negative genetic testing
      for neurofibromatosis Type 1 and no clinical evidence of neurofibromatosis Type 2
      or schwannomatosis.   A 28-year-old woman presented with tentatively diagnosed
      schwannomatosis. She had painful bilateral retromastoid scalp tumors as well as
      multiple other painful tumors in the distribution of the saphenous, femoral, and
      sciatic nerves. Her family history was significant for a paternal grandfather
      with a solitary schwannoma. The patient underwent multiple surgical procedures
      for tumor resection, including tumors in the regions of the retromastoid scalp,
      bilateral sciatic nerves, left femoral nerve, and left axilla. These tumors were
      examined and evaluated histologically. Within the tumors, components of both
      neurofibromas and schwannomas were found, even though these 2 peripheral nerve
      sheath tumors have been long considered to be distinct entities. This case report
      suggests a distinct syndrome that has not previously been appreciated.

PMID- 22978540
TI  - Normalization of hindbrain morphology after decompression of Chiari malformation
      Type I.
AB  - OBJECT: Chiari malformation Type I (CM-I) is characterized by hindbrain
      deformity. We investigated the effects of craniocervical decompression surgery on
      the anatomical features of hindbrain deformity with a prospective MRI study of
      patients with CM-I. METHODS: A prospective longitudinal study was conducted in 48
      patients with CM-I (39 with syringomyelia) treated with craniocervical
      decompression. Clinical examinations and cervical MRI were performed before
      surgery and 1 week, 3-6 months, and annually after surgery. Hindbrain deformity
      was defined by tonsillar ectopia, pointed cerebellar tonsils, and/or
      cervicomedullary protuberance. The length of the clivus, basiocciput
      (sphenooccipital synchondrosis to basion), supraocciput (internal occipital
      protuberance to opisthion), and anteroposterior (AP) width of CSF pathways at the
      foramen magnum were measured and compared with those from 18 healthy volunteers
      (control group). RESULTS: Before surgery, the patients' posterior fossa bones
      were short and their CSF pathways were narrow. All patients had tonsillar ectopia
      (mean [+/- SD] 12.3 +/- 5.1 mm; normal 0.3 +/- 1.0). The majority of patients had
      pointed tonsils and more than two-thirds exhibited a cervicomedullary
      protuberance. Clivus and basiocciput lengths were significantly shorter than the
      values obtained in the control group. However, the supraocciput length did not
      differ significantly from control measurements. The mean bulbopontine sulcus
      distance superior to the basion was 9.5 +/- 2.6 mm (vs 13.6 +/- 2.8 mm in
      controls; p < 0.0001). The AP widths of the CSF pathways at the level of the
      foramen magnum were significantly narrowed. After surgery, CSF pathways
      significantly expanded both ventrally and dorsally. By 3-6 months after surgery,
      pointed tonsils became round, cervicomedullary protuberance disappeared, and
      tonsillar ectopia diminished by 51% (to 6.0 +/- 3.3 mm; p < 0.0001). CONCLUSIONS:
      The cerebellar tonsils and brainstem assumed a normal appearance within 6 months
      after craniocervical decompression. These findings support the concept that the
      CM-I is not a congenital malformation of the neural elements but rather an
      acquired malformation that arises from pulsatile impaction of the cerebellar
      tonsils into the foramen magnum. Clinical trial registration no.: NCT00001327.

PMID- 22978541
TI  - Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas.
AB  - OBJECT: Microsurgical management of foramen magnum meningiomas (FMMs) can be
      associated with significant morbidity and mortality. Stereotactic radiosurgery
      may be an efficient and safe alternative treatment modality for such tumors. The
      object of this study was to increase the documented experience with Gamma Knife
      surgery (GKS) for FMMs and to delineate its role in an overall management
      paradigm. METHODS: The authors report on their experience with 24 patients
      harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors,
      5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual
      tumors after a prior surgery. RESULTS: Follow-up clinical and imaging data were
      available in 21 patients at a median follow-up of 47 months (range 3-128 months).
      Ten patients had measurable tumor regression, which was defined as an overall
      volume reduction > 25%. Eleven patients had no further tumor growth. Two patients
      died as a result of advanced comorbidities before follow-up imaging. One patient
      was living 8 years after GKS but had no clinical evaluation. Ten of 17
      symptomatic patients with at least 6 months of follow-up had symptom improvement,
      and 7 remained clinically stable. Smaller tumors were more likely to regress. No
      patient suffered an adverse radiation effect after radiosurgery. CONCLUSIONS:
      Gamma Knife surgery was a safe management strategy for small, minimally
      symptomatic, or growing FMMs as well as for residual tumors following
      conservative microsurgical removal.

PMID- 22978542
TI  - Efficacy of vagus nerve stimulation in posttraumatic versus nontraumatic
      epilepsy.
AB  - OBJECT: In the US, approximately 500,000 individuals are hospitalized yearly for
      traumatic brain injury (TBI), and posttraumatic epilepsy (PTE) is a common
      sequela of TBI. Improved treatment strategies for PTE are critically needed, as
      patients with the disorder are often resistant to antiepileptic medications and
      are poor candidates for definitive resection. Vagus nerve stimulation (VNS) is an
      adjunctive treatment for medically refractory epilepsy that results in a >= 50%
      reduction in seizure frequency in approximately 50% of patients after 1 year of
      therapy. The role of VNS in PTE has been poorly studied. The aim of this study
      was to determine whether patients with PTE attain more favorable seizure outcomes
      than individuals with nontraumatic epilepsy etiologies. METHODS: Using a case
      control study design, the authors retrospectively compared seizure outcomes after
      VNS therapy in patients with PTE versus those with nontraumatic epilepsy (non
      PTE) who were part of a large prospectively collected patient registry. RESULTS:
      After VNS therapy, patients with PTE demonstrated a greater reduction in seizure
      frequency (50% fewer seizures at the 3-month follow-up; 73% fewer seizures at 24
      months) than patients with non-PTE (46% fewer seizures at 3 months; 57% fewer
      seizures at 24 months). Overall, patients with PTE had a 78% rate of clinical
      response to VNS therapy at 24 months (that is, >= 50% reduction in seizure
      frequency) as compared with a 61% response rate among patients with non-PTE (OR
      1.32, 95% CI 1.07-1.61), leading to improved outcomes according to the Engel
      classification (p < 0.0001, Cochran-Mantel-Haenszel statistic). CONCLUSIONS:
      Vagus nerve stimulation should be considered in patients with medically
      refractory PTE who are not good candidates for resection. A controlled
      prospective trial is necessary to further examine seizure outcomes as well as
      neuropsychological outcomes after VNS therapy in patients with intractable PTE.

PMID- 22978543
TI  - Neoplastic meningitis.

PMID- 22978544
TI  - Girly mags and girly jobs: pornography and gendered inequality in forensic
      practice.
AB  - This article presents findings from a discourse analytic study into the
      constructive nature and textual variations of language in a high-security
      hospital. It explores how mental health nurses, and men convicted of sexual
      offences who also have a diagnosis of personality disorder, talked about
      pornography and sexual crime in the context of forensic provision. Access to
      sexually-explicit media, in relation to treatment environments for people
      convicted of sexual offences, has become a cause for professional and political
      concern in the UK. Data collection and analysis, undertaken concurrently, were
      informed by a discursive design. Semistructured interviews, as co-constructed
      accounts with nursing staff and detained patients, were audio-taped and
      transcribed. Data were coded to identify the discursive repertoires, or
      collective talk, of respondents. In contrast to empirical inquiry into
      pornography and sexual violence, methodology shifted attention from measurement
      to meaning, and situated research in a clinical domain. The findings focus on
      performative language use, where talk about pornography textured the treatment
      environment, contributed to an overtly masculine discourse, framed the ward as
      male space, and promoted gendered inequality. The discussion questions the
      legitimacy of the therapeutic enterprise.

PMID- 22978545
TI  - Effect of biofilm age on settlement of Mytilus edulis.
AB  - Biofilm ageing is commonly assumed to improve mussel settlement on artificial
      substrata, but the structure and taxonomic composition of biofilms remains
      unclear. In the present study, multi-species biofilms were characterized at
      different ages (1, 2, and 3 weeks) and their influence on settlement of the blue
      mussel, Mytilus edulis, was tested in the field. As biofilms can constitute a
      consistent food resource for larvae, the lipid quality, defined as the proportion
      of related essential fatty acids, may be a selection criterion for settlement.
      Overall mussel settlement increased on biofilms older than 1 week, and the
      enhanced settlement corresponded to the abundance and composition of the biofilm
      community, rather than to essential fatty acid levels. However, during a pulse of
      phytoplankton, the positive influence of biofilm was not detected, suggesting
      that pelagic cues overwhelmed those associated with biofilms. The influence of
      biofilms on mussel settlement could be more crucial when planktonic resources are
      limited.

PMID- 22978546
TI  - Factors associated with the number of consultations per dietetic treatment: an
      observational study.
AB  - BACKGROUND: Greater understanding of the variance in the number of consultations
      per dietetic treatment will increase the transparency of dietetic healthcare.
      Substantial inter-practitioner variation may suggest a potential to increase
      efficiency and improve quality. It is not known whether inter-practitioner
      variation also exists in the field of dietetics. Therefore, the aims of this
      study are to examine inter-practitioner variation in the number of consultations
      per treatment and the case-mix factors that explain this variation. METHODS: For
      this observational study, data were used from the National Information Service
      for Allied Health Care (LiPZ). LiPZ is a Dutch registration network of allied
      health care professionals, including dietitians working in primary healthcare.
      Data were used from 6,496 patients who underwent dietetic treatment between 2006
      and 2009, treated by 27 dietitians working in solo practices located throughout
      the Netherlands. Data collection was based on the long-term computerized
      registration of healthcare-related information on patients, reimbursement,
      treatment and health problems, using a regular software program for
      reimbursement. Poisson multilevel regression analyses were used to model the
      number of consultations and to account for the clustered structure of the data.
      RESULTS: After adjusting for case-mix, seven percent of the total variation in
      consultation sessions was due to dietitians. The mean number of consultations per
      treatment was 4.9 and ranged from 2.3-10.1 between dietitians. Demographic
      characteristics, patients' initiative and patients' health problems explained 28%
      of the inter-practitioner variation. Certain groups of patients used
      significantly more dietetic healthcare compared to others, i.e. older patients,
      females, the native Dutch, patients with a history of dietetic healthcare,
      patients who started the treatment on their own initiative, patients with
      multiple diagnoses, overweight, or binge eating disorder. CONCLUSIONS:
      Considerable variation in number of consultations per dietetic treatment is due
      to dietitians. Some of this inter-practitioner variation was reduced after
      adjusting for case-mix. Further research is necessary to study the relation
      between inter-practitioner variation and the effectiveness and quality of
      dietetic treatment.

PMID- 22978547
TI  - Clinical indices of familial alcohol use disorder.
AB  - BACKGROUND: Alcohol use disorders (AUDs) are clinically heterogeneous and
      strongly influenced by familial/genetic factors. Can we identify specific
      clinical features of AUDs that index familial liability to illness? METHODS: In
      twins from the Virginia Adult Twin Study of Psychiatric and Substance Use
      Disorders meeting DSM-IV criteria for lifetime AUDs, we examined whether clinical
      features of AUDs, including individual DSM-IV criteria for alcohol dependence
      (AD) and alcohol abuse (AA), predicted risk for AUDs in cotwins and/or parents.
      Analyses of individual criterion were repeated controlling for the total number
      of endorsed criteria. RESULTS: Across these analyses, examining narrowly and
      broadly defined AUDs, risk of AUDs in relatives was more consistently predicted
      by abuse criteria than by dependence criteria, and by criteria reflecting
      negative psychosocial consequences rather than pharmacologic/biological criteria.
      Age at onset (AAO) poorly predicted risk in relatives. AUD associated legal
      problems, the one criterion slated for removal in DSM-5, was the most consistent
      single predictor of familial risk. Associations observed between individual
      criteria and risks of illness in relatives were generally stronger in monozygotic
      than dizygotic twin pairs, suggesting that these symptoms reflect a genetic risk
      for AUDs. CONCLUSIONS: Individual DSM-IV criteria for AA and AD differ
      meaningfully in the degree to which they reflect the familial/genetic liability
      to AUDs. Contrary to expectation, the familial/genetic risk to AUDs was better
      reflected by symptoms of abuse and negative psychosocial consequences of AUD than
      by early AAO, or symptoms of tolerance and withdrawal.

PMID- 22978548
TI  - By increasing the affinity of heparin for fibrin, Zn(2+) promotes the formation
      of a ternary heparin-thrombin-fibrin complex that protects thrombin from
      inhibition by antithrombin.
AB  - Heparin binds fibrin and, by bridging thrombin onto fibrin, promotes the
      formation of a ternary heparin-thrombin-fibrin complex that protects thrombin
      from inhibition by antithrombin. Because thrombin binds gamma(A)/gamma'-fibrin, a
      variant with an extended gamma-chain, with higher affinity than the bulk
      gamma(A)/gamma(A)-fibrin, gamma(A)/gamma'-fibrin affords bound thrombin more
      protection from inhibition by antithrombin-heparin. We examined the effect of
      Zn(2+) on heparin-thrombin-fibrin complex formation because Zn(2+) modulates
      heparin-protein interactions. Zn(2+) increased the affinity of heparin for
      gamma(A)/gamma(A)- and gamma(A)/gamma'-fibrin by 4.3- and 3.7-fold, respectively,
      but had no effect on the affinity of thrombin for either form of fibrin. In
      contrast, in the presence of heparin, Zn(2+) increased the affinity of thrombin
      for gamma(A)/gamma(A)-fibrin 4-fold (from a K(d) value of 0.8 to 0.2 MUM) and
      slowed the rate of thrombin dissociation from gamma(A)/gamma(A)-fibrin clots.
      These findings suggest that Zn(2+) enhances the formation of ternary heparin
      thrombin-fibrin complexes with gamma(A)/gamma(A)-fibrin but does not influence
      the already high affinity interaction of thrombin with gamma(A)/gamma'-fibrin.
      Consistent with this concept, in the presence of Zn(2+), gamma(A)/gamma(A)-fibrin
      protected thrombin from inhibition by antithrombin-heparin to a similar extent as
      gamma(A)/gamma'-fibrin. Therefore, by enhancing the binding of heparin to fibrin,
      physiological concentrations of Zn(2+) render fibrin-bound thrombin more
      protected from inhibition by antithrombin. Because fibrin-bound thrombin can
      trigger thrombus expansion, these findings help to explain why recurrent
      thrombosis can occur despite heparin treatment.

PMID- 22978549
TI  - ESCRT-II's involvement in HIV-1 genomic RNA trafficking and assembly.
AB  - BACKGROUND INFORMATION: Several host proteins play crucial roles in the HIV-1
      replication cycle. The endosomal sorting complex required for transport (ESCRT)
      exemplifies a large, multi-component host machinery that is required by HIV-1 for
      viral budding. ESCRT promotes the inward budding of vesicles from the membranes
      of late endosomes to generate multi-vesicular bodies. However, HIV-1 co-opts the
      ESCRT to enable outwards budding of virus particles from the plasma membrane, a
      phenomenon that is topologically similar to multi-vesicular body biogenesis. A
      role for ESCRTII in mRNA trafficking has been established in Drosophila in which
      the ESCRT-II components, Vps22 and Vps36, promote the localisation of the bicoid
      mRNA in the fertilised egg. This is achieved via specific interactions with the
      Staufen protein. In this work, we investigated a possible implication of ESCRT-II
      in the HIV-1 replication cycle. RESULTS: Co-immunoprecipitation analyses and live
      cell tri-molecular fluorescence complementation assays revealed that interactions
      between EAP30 and Gag and another between EAP30 and Staufen1 occur in mammalian
      cells. We then depleted EAP30 (the orthologue for Vps22) by siRNA to target ESCRT
      II in HIV-1 expressing cells. This treatment disrupted ESCRT-II function and
      leads to the degradation of the two other ESCRT-II complex proteins, EAP45 and
      EAP20, as well as the associated Rab7-interacting lysosomal protein. The
      depletion of EAP30 led to dramatically reduced viral structural protein Gag and
      virus production levels, without any effect on viral RNA levels. On the contrary,
      the overexpression of EAP30 led to a several-fold increase in virus production.
      Unexpec-tedly, siRNA-mediated depletion of EAP30 led to a block to HIV-1 genomic
      RNA trafficking and resulted in the accumulation of genomic RNA in the nucleus
      and juxtanuclear domains. CONCLUSIONS: Our data provide the first evidence that
      the Staufen1-ESCRT-II interaction is evolutionarily conserved from lower to
      higher eukaryotes and reveal a novel role for EAP30 in the control of HIV-1 RNA
      trafficking and gene expression.

PMID- 22978551
TI  - Community involvement among behaviourally bisexual men in the Midwestern USA:
      experiences and perceptions across communities.
AB  - Limited research exists regarding community involvement and social support among
      behaviourally bisexual men. Previous studies suggest that bisexual men experience
      high levels of social stigma in both heterosexual and homosexual community
      settings. Research focusing on social support has demonstrated that individuals
      with limited access to similar individuals experience greater risk for negative
      health outcomes. Using a community-based research design, participants were
      recruited using multiple methods. Researchers conducted in-depth, semi-structured
      interviews with 75 men who reported having engaged in bisexual behaviour within
      the past six months. Interviews elucidated the experiences of behaviourally
      bisexual men in heterosexual and homosexual settings, as well as their
      perceptions of the existence of a bisexual community or bisexual spaces. All
      participants perceived a lack of a visible bisexual community and expressed
      difficulty with being comfortable, or a feeling of belonging, within a variety of
      heterosexual and homosexual community spaces. Findings suggest the need for
      interventions focused on community building among, as well as creating spaces
      specifically designed for, bisexual men in order to increase perceived social
      support and decrease isolation and possible negative health outcomes.

PMID- 22978550
TI  - Identification of ligand templates using local structure alignment for structure
      based drug design.
AB  - With a rapid increase in the number of high-resolution protein-ligand structures,
      the known protein-ligand structures can be used to gain insight into ligand
      binding modes in a target protein. On the basis of the fact that the structurally
      similar binding sites share information about their ligands, we have developed a
      local structure alignment tool, G-LoSA (graph-based local structure alignment).
      The known protein-ligand binding-site structure library is searched by G-LoSA to
      detect binding-site structures with similar geometry and physicochemical
      properties to a query binding-site structure regardless of sequence continuity
      and protein fold. Then, the ligands in the identified complexes are used as
      templates (i.e., template ligands) to predict/design a ligand for the target
      protein. The performance of G-LoSA is validated against 76 benchmark targets from
      the Astex diverse set. Using the currently available protein-ligand structure
      library, G-LoSA is able to identify a single template ligand (from a
      nonhomologous protein complex) that is highly similar to the target ligand in
      more than half of the benchmark targets. In addition, our benchmark analyses show
      that an assembly of structural fragments from multiple template ligands with
      partial similarity to the target ligand can be used to design novel ligand
      structures specific to the target protein. This study clearly indicates that a
      template-based ligand modeling has potential for de novo ligand design and can be
      a complementary approach to the receptor structure based methods.

PMID- 22978552
TI  - High pressure synthesis and superconductivity of the ternary compounds Mg(Mg(1
      x)Al(x))Si with the anticotunnite structure.
AB  - Ternary compounds Mg(Mg(1-x)Al(x))Si (0.3 < x < 0.8) have been prepared under
      high pressure and high temperature conditions of 5 GPa at 800-1100  degrees C.
      The single crystal study revealed that the compound (x = 0.45) is isomorphous
      with the anticotunnite, or the TiNiSi structure, and crystallizes with space
      group Pnma, with lattice parameters a = 6.9242(2), b = 4.1380(1), c = 7.9618(2)
      A, and Z = 4. The compound with x > 0.5 shows superconductivity with a transition
      temperature (T(c)) ~ 6 K. The compound is a peritectic solid solution associated
      with other phases such as Mg(9)Si(5), Al, and Si, depending on cooling protocols
      in the preparation. The band structure calculation on the composition MgAlSi
      suggests that the Al and Mg orbitals mainly contribute to the density of states
      near the Fermi level, and the substitution of Mg with Al favors the
      superconductivity.

PMID- 22978554
TI  - Urticaria-like follicular mucinosis: four new cases of a controversial entity.

PMID- 22978557
TI  - Molecular epidemiology of Enterococcus cecorum isolates recovered from
      enterococcal spondylitis outbreaks in the southeastern United States.
AB  - Enterococcus cecorum, a normal intestinal inhabitant, is increasingly responsible
      for outbreaks of arthritis and osteomyelitis in chickens worldwide. Enterococcal
      spondylitis (ES) is a specific manifestation of E. cecorum-associated disease in
      which increased flock morbidity and mortality result from chronic infection
      involving the free thoracic vertebra. In this study the genetic relatedness and
      antimicrobial resistance of isolates recovered from ES-affected flocks in the
      southeastern United States were determined. ES outbreaks from 2007 to 2011 were
      investigated in North Carolina (15 flocks, 13 farms, four integrators), South
      Carolina (one flock, one farm, one integrator) and Alabama (six flocks, six
      farms, one integrator). From these 22 epidemiologically distinct outbreaks, 326
      isolates of E. cecorum were recovered. Isolates from spinal lesions and caeca of
      affected birds (cases) and caeca of unaffected birds (controls) were genotyped
      using pulsed-field gel electrophoresis; phenotyped using both GenIII MicroPlateTM
      (Biolog; Hayward, CA, USA) microbial identification plates and antimicrobial
      sensitivity testing; and compared with each other. Isolates from spinal lesions
      were incapable of mannitol metabolism and the majority of these isolates were
      genetically clonal. In contrast, caecal isolates from control birds varied in
      their ability to metabolize mannitol and were genetically diverse. Isolates from
      both case and control birds had high levels of antimicrobial resistance. These
      findings indicate that the increase in E. cecorum-associated disease in the
      southeast United States is due to the emergence of new clones with increased
      pathogenicity and multidrug resistance.

PMID- 22978556
TI  - PCR based bronchoscopic detection of common respiratory pathogens in chronic
      cough: a case control study.
AB  - BACKGROUND: Viral respiratory tract infection is the most frequent cause of
      acute cough and is reported at onset in about one third of patients with chronic
      cough. Persistent infection is therefore one possible explanation for the cough
      reflex hypersensitivity and pulmonary inflammation reported in chronic cough
      patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar
      lavage cell counts were obtained from ten healthy volunteers and twenty treatment
      resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen
      for known respiratory pathogens was performed on biopsy tissue. Chronic cough
      patients also underwent cough reflex sensitivity testing using citric acid.
      RESULTS: There was no significant difference in incidence of infection between
      healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and
      lymphocytic groups (p = 0.404). BAL cell percentages were not significantly
      different between healthy volunteers and chronic cough patients without
      lymphocytosis. Lymphocytic patients however had a significantly raised percentage
      of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and
      decreased macrophages (p < 0.001) verses healthy volunteers. There was no
      significant difference in the cough reflex sensitivity between non-lymphocytic
      and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent
      infection in the lung is unlikely to play an important role in chronic cough, but
      a role for undetected or undetectable pathogens in either the lung or a distal
      site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials
      ISRCTN62337037 & ISRCTN40147207.

PMID- 22978558
TI  - Genome wide identification of chilling responsive microRNAs in Prunus persica.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small RNAs (sRNAs) approximately 21
      nucleotides in length that negatively control gene expression by cleaving or
      inhibiting the translation of target gene transcripts. Within this context,
      miRNAs and siRNAs are coming to the forefront as molecular mediators of gene
      regulation in plant responses to annual temperature cycling and cold stress. For
      this reason, we chose to identify and characterize the conserved and non
      conserved miRNA component of peach (Prunus persica (L.) Batsch) focusing our
      efforts on both the recently released whole genome sequence of peach and sRNA
      transcriptome sequences from two tissues representing non-dormant leaves and
      dormant leaf buds. Conserved and non-conserved miRNAs, and their targets were
      identified. These sRNA resources were used to identify cold-responsive miRNAs
      whose gene targets co-localize with previously described QTLs for chilling
      requirement (CR). RESULTS: Analysis of 21 million peach sRNA reads allowed us to
      identify 157 and 230 conserved and non-conserved miRNA sequences. Among the non
      conserved miRNAs, we identified 205 that seem to be specific to peach.
      Comparative genome analysis between peach and Arabidopsis showed that conserved
      miRNA families, with the exception of miR5021, are similar in size. Sixteen of
      these conserved miRNA families are deeply rooted in land plant phylogeny as they
      are present in mosses and/or lycophytes. Within the other conserved miRNA
      families, five families (miR1446, miR473, miR479, miR3629, and miR3627) were
      reported only in tree species (Populustrichocarpa, Citrus trifolia, and Prunus
      persica). Expression analysis identified several up-regulated or down-regulated
      miRNAs in winter buds versus young leaves. A search of the peach proteome allowed
      the prediction of target genes for most of the conserved miRNAs and a large
      fraction of non-conserved miRNAs. A fraction of predicted targets in peach have
      not been previously reported in other species. Several conserved and non
      conserved miRNAs and miRNA-regulated genes co-localize with Quantitative Trait
      Loci (QTLs) for chilling requirement (CR-QTL) and bloom date (BD-QTL).
      CONCLUSIONS: In this work, we identified a large set of conserved and non
      conserved miRNAs and describe their evolutionary footprint in angiosperm
      lineages. Several of these miRNAs were induced in winter buds and co-localized
      with QTLs for chilling requirement and bloom date thus making their gene targets
      potential candidates for mediating plant responses to cold stress. Several peach
      homologs of genes participating in the regulation of vernalization in Arabidopsis
      were identified as differentially expressed miRNAs targets, potentially linking
      these gene activities to cold responses in peach dormant buds. The non-conserved
      miRNAs may regulate cellular, physiological or developmental processes specific
      to peach and/or other tree species.

PMID- 22978555
TI  - Do diet and taxonomy influence insect gut bacterial communities?
AB  - Many insects contain diverse gut microbial communities. While several studies
      have focused on a single or small group of species, comparative studies of
      phylogenetically diverse hosts can illuminate general patterns of host-microbiota
      associations. In this study, we tested the hypotheses that (i) host diet and (ii)
      host taxonomy structure intestinal bacterial community composition among insects.
      We used published 16S rRNA gene sequence data for 58 insect species in addition
      to four beetle species sampled from the Sevilleta National Wildlife Refuge to
      test these hypotheses. Overall, gut bacterial species richness in these insects
      was low. Decaying wood xylophagous insects harboured the richest bacterial gut
      flora (102.8 species level operational taxonomic units (OTUs)/sample +/- 71.7,
      11.8 +/- 5.9 phylogenetic diversity (PD)/sample), while bees and wasps harboured
      the least rich bacterial communities (11.0 species level OTUs/sample +/- 5.4, 2.6
      +/- 0.8 PD/sample). We found evidence to support our hypotheses that host diet
      and taxonomy structure insect gut bacterial communities (P < 0.001 for both).
      However, while host taxonomy was important in hymenopteran and termite gut
      community structure, diet was an important community structuring factor
      particularly for insect hosts that ingest lignocellulose-derived substances. Our
      analysis provides a baseline comparison of insect gut bacterial communities from
      which to test further hypotheses concerning proximate and ultimate causes of
      these associations.

PMID- 22978559
TI  - Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and
      anti-citrullinated protein antibodies in human gingiva.
AB  - BACKGROUND AND OBJECTIVE: The presence of citrullinated proteins, and
      peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal
      tissues, determine the presence of anti-cyclic citrullinated protein antibodies
      (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these
      proteins between inflamed and non-inflamed sites. MATERIAL AND METHODS: Tissue
      sections were stained using antibodies against citrullinated proteins, PAD-2 and
      PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and
      non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid
      were detected by ELISA. RESULTS: Citrullinated proteins, PAD-2 and PAD-4 were
      detected in gingiva. There was a correlation between inflammation and expression
      of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and
      non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of
      individuals with periodontitis. CONCLUSION: PAD-2 and PAD-4 (protein and mRNA) as
      well as citrullinated proteins are present in inflamed gingiva, and anti-CCP
      antibodies can be detected in the GCF of some patients. Tissue expression of
      citrullinated proteins and PAD increased with the severity of inflammation. The
      presence of anti-CCP antibodies in GCF was almost exclusive to a subset of
      patients with periodontitis. Increased expression of these proteins in inflamed
      gingiva lends support to the notion that periodontal inflammation contributes to
      the inflammatory burden in a similar way to rheumatoid arthritis.

PMID- 22978560
TI  - Formation of oligomers in the early phase of pH-induced aggregation of the
      Alzheimer Abeta(12-28) peptide [corrected].
AB  - The early phase in the aggregation process of the Alzheimer's peptide Abeta(12
      28) with both protected and unprotected ends was studied by time-resolved
      infrared spectroscopy and circular dichroism spectroscopy. Aggregation in the
      time-resolved experiments was initiated by a rapid pH drop caused by the
      photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate). The infrared
      spectra indicate aggregates from both versions of the Abeta(12-28) peptide.
      [corrected] They form fast (within 60 ms), presumably from initial aggregates,
      and their spectral signature is consistent with a beta-barrel structure. The
      other type arises relatively slowly from unstructured monomers on the seconds-to
      minutes time scale and forms at lower pH than the first type. These beta sheets
      are antiparallel, planar, and large and show an absorption band at 1622 cm(-1)
      that shifts to 1617 cm(-1) in 12 min with most of the shift occurring in 10 s.

PMID- 22978553
TI  - Oxygen consumption and usage during physical exercise: the balance between
      oxidative stress and ROS-dependent adaptive signaling.
AB  - The complexity of human DNA has been affected by aerobic metabolism, including
      endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an
      important role in the evolution of Homo sapiens, and oxygen was not important
      just for survival, but it was crucial to redox-mediated adaptation. The metabolic
      challenge during physical exercise results in an elevated generation of reactive
      oxygen species (ROS) that are important modulators of muscle contraction,
      antioxidant protection, and oxidative damage repair, which at moderate levels
      generate physiological responses. Several factors of mitochondrial biogenesis,
      such as peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC
      1alpha), mitogen-activated protein kinase, and SIRT1, are modulated by exercise
      associated changes in the redox milieu. PGC-1alpha activation could result in
      decreased oxidative challenge, either by upregulation of antioxidant enzymes
      and/or by an increased number of mitochondria that allows lower levels of
      respiratory activity for the same degree of ATP generation. Endogenous thiol
      antioxidants glutathione and thioredoxin are modulated with high oxygen
      consumption and ROS generation during physical exercise, controlling cellular
      function through redox-sensitive signaling and protein-protein interactions.
      Endurance exercise-related angiogenesis, up to a significant degree, is regulated
      by ROS-mediated activation of hypoxia-inducible factor 1alpha. Moreover, the
      exercise-associated ROS production could be important to DNA methylation and post
      translation modifications of histone residues, which create heritable adaptive
      conditions based on epigenetic features of chromosomes. Accumulating data
      indicate that exercise with moderate intensity has systemic and complex health
      promoting effects, which undoubtedly involve regulation of redox homeostasis and
      signaling.

PMID- 22978561
TI  - Ending homelessness among people with mental illness: the At Home/Chez Soi
      randomized trial of a Housing First intervention in Toronto.
AB  - BACKGROUND: The At Home/Chez Soi (AH/CS) Project is a randomized controlled trial
      of a Housing First intervention to meet the needs of homeless individuals with
      mental illness in five cities across Canada. The objectives of this paper are to
      examine the approach to participant recruitment and community engagement at the
      Toronto site of the AH/CS Project, and to describe the baseline demographics of
      participants in Toronto. METHODS: Homeless individuals (n = 575) with either high
      needs (n = 197) or moderate needs (n = 378) for mental health support were
      recruited through service providers in the city of Toronto. Participants were
      randomized to Housing First interventions or Treatment as Usual (control) groups.
      Housing First interventions were offered at two different mental health service
      delivery levels: Assertive Community Treatment for high needs participants and
      Intensive Case Management for moderate needs participants. Demographic data were
      collected via quantitative questionnaires at baseline interviews. RESULTS: The
      effectiveness of the recruitment strategy was influenced by a carefully designed
      referral system, targeted recruitment of specific groups, and an extensive
      network of pre-existing services. Community members, potential participants,
      service providers, and other stakeholders were engaged through active outreach
      and information sessions. Challenges related to the need for different sectors to
      work together were resolved through team building strategies. Randomization
      produced similar demographic, mental health, cognitive and functional impairment
      characteristics in the intervention and control groups for both the high needs
      and moderate needs groups. The majority of participants were male (69%), aged >40
      years (53%), single/never married (69%), without dependent children (71%), born
      in Canada (54%), and non-white (64%). Many participants had substance dependence
      (38%), psychotic disorder (37%), major depressive episode (36%), alcohol
      dependence (29%), post-traumatic stress disorder (PTSD) (23%), and mood disorder
      with psychotic features (21%). More than two-thirds of the participants (65%)
      indicated some level of suicidality. CONCLUSIONS: Recruitment at the Toronto site
      of AH/CS project produced a sample of participants that reflects the diverse
      demographics of the target population. This study will provide much needed data
      on how to best address the issue of homelessness and mental illness in Canada.

PMID- 22978562
TI  - Dynamics of microRNAs in bull spermatozoa.
AB  - BACKGROUND: MicroRNAs are small non-coding RNAs that regulate gene expression and
      thus play important roles in mammalian development. However, the comprehensive
      lists of microRNAs, as well as, molecular mechanisms by which microRNAs regulate
      gene expression during gamete and embryo development are poorly defined. The
      objectives of this study were to determine microRNAs in bull sperm and predict
      their functions. METHODS: To accomplish our objectives we isolated miRNAs from
      sperm of high and low fertility bulls, conducted microRNA microarray experiments
      and validated expression of a panel of microRNAs using real time RT-PCR.
      Bioinformatic approaches were carried out to identify regulated targets. RESULTS:
      We demonstrated that an abundance of microRNAs were present in bovine
      spermatozoa, however, only seven were differentially expressed; hsa-aga-3155, 
      8197, -6727, -11796, -14189, -6125, -13659. The abundance of miRNAs in the
      spermatozoa and the differential expression in sperm from high vs. low fertility
      bulls suggests that the miRNAs possibly play important functions in the
      regulating mechanisms of bovine spermatozoa. CONCLUSION: Identification of
      specific microRNAs expressed in spermatozoa of bulls with different fertility
      phenotypes will help better understand mammalian gametogenesis and early
      development.

PMID- 22978563
TI  - Sorafenib and its derivative SC-49 sensitize hepatocellular carcinoma cells to CS
      1008, a humanized anti-TNFRSF10B (DR5) antibody.
AB  - BACKGROUND AND PURPOSE: Previously, we have shown that sorafenib sensitizes
      hepatocellular carcinoma (HCC) to apoptosis induced by TNF-related apoptosis
      inducing ligand (TNFSF10; TRAIL). Here, we report that sorafenib and SC-49
      sensitize HCC cells to CS-1008, a novel anti-human death receptor 5 (TNFRSF10B)
      antibody. EXPERIMENTAL APPROACH: HCC cell lines (PLC5, Huh-7, and Hep3B) were
      treated with CS-1008 and/or sorafenib and analysed in terms of apoptosis and
      signal transductions. KEY RESULTS: SC-49 is a sorafenib derivative, which is
      devoid of kinase inhibitory activity. Both sorafenib and SC-49 down-regulated the
      phosphorylation of STAT3 at Tyr(705)  and subsequently reduced the levels of
      STAT3-regulated proteins, Mcl-1, survivin and cylcin D1, in CS-1008-treated HCC
      cells. Knockdown of STAT3 by RNA interference overcame apoptotic resistance to CS
      1008 in HCC cells, and ectopic expression of STAT3 in HCC cells abolished the
      sensitizing effects of sorafenib and SC-49 on CS-1008-induced apoptosis,
      indicating that inhibition of STAT3 mediates the enhancing effects of these
      compounds when combined with CS-1008. Importantly, inhibition of SHP-1 by adding
      a specific SHP-1 inhibitor reduced the effects of SC-49 and CS-1008 on p-STAT3
      and apoptosis, whereas co-treatment of CS-1008 with SC-49 increased the activity
      of SHP-1. These data indicate that the combined effects of CS-1008 and SC-49 on
      HCC are mediated by SHP-1. Moreover, the combination of CS-1008 and SC-49
      inhibited HCC xenograft tumour growth in vivo. CONCLUSIONS AND IMPLICATIONS:
      Sorafenib and its derivative SC-49 sensitize HCC cells to the antitumour effects
      of CS-1008 through SHP-1-dependent inactivation of STAT3.

PMID- 22978564
TI  - Embalmed and fresh frozen human bones in orthopedic cadaveric studies: which bone
      is authentic and feasible?
AB  - BACKGROUND AND PURPOSE: The most frequently used bones for mechanical testing of
      orthopedic and trauma devices are fresh frozen cadaveric bones, embalmed
      cadaveric bones, and artificial composite bones. Even today, the comparability of
      these different bone types has not been established. METHODS: We tested fresh
      frozen and embalmed cadaveric femora that were similar concerning age, sex, bone
      mineral density, and stiffness. Artificial composite femora were used as a
      reference group. Testing parameters were pullout forces of cortex and cancellous
      screws, maximum load until failure, and type of fracture generated. RESULTS:
      Stiffness and type of fracture generated (Pauwels III) were similar for all 3
      bone types (fresh frozen: 969 N/mm, 95% confidence interval (CI): 897-1,039;
      embalmed: 999 N/mm, CI: 875-1,121; composite: 946 N/mm, CI: 852-1,040).
      Furthermore, no significant differences were found between fresh frozen and
      embalmed femora concerning pullout forces of cancellous screws (fresh frozen: 654
      N, CI: 471-836; embalmed: 595 N, CI: 365-823) and cortex screws (fresh frozen:
      1,152 N, CI: 894-1,408; embalmed: 1,461 N, CI: 880-2,042), and axial load until
      failure (fresh frozen: 3,427 N, CI: 2,564-4290; embalmed: 3,603 N, CI: 2,898
      4,306). The reference group showed statistically significantly different results
      for pullout forces of cancellous screws (2,344 N, CI: 2,068-2,620) and cortex
      screws (5,536 N, CI: 5,203-5,867) and for the axial load until failure (> 7,952
      N). INTERPRETATION: Embalmed femur bones and fresh frozen bones had similar
      characteristics by mechanical testing. Thus, we suggest that embalmed human
      cadaveric bone is a good and safe option for mechanical testing of orthopedic and
      trauma devices.

PMID- 22978565
TI  - Two novel NPM1 mutations in an acute myeloid leukemia patient transformed from
      primary myelofibrosis.

PMID- 22978567
TI  - Spending too much: relationships with borderline personality symptomatology.
AB  - OBJECTIVE: Few studies have examined spending behaviors in individuals with
      borderline personality symptomatology (BPS) - the focus of the present study.
      Method. Summing four cross-sectional samples totaling 1122 consecutive patients
      being seen in an internal medicine clinic, and using a self-report survey
      methodology, we examined relationships between excessive spending and BPS, using
      two measures for this Axis II disorder. RESULTS: The endorsement of excessive
      spending demonstrated statistically significant correlations with both measures
      of BPS (0.40 and 0.49), and individuals who exceeded the established cut-off
      scores on both measures were statistically significantly more likely to endorse
      excessive spending. CONCLUSIONS: Excessive spending demonstrates empirical
      relationships with BPS and appears to be a clinical area of inquiry in BPS
      regarding self-regulation difficulties.

PMID- 22978568
TI  - White matter volume is decreased in the brain of patients with neuromyelitis
      optica.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease involving
      predominantly the spinal cord and optic nerves. Whether patients with NMO have a
      loss in white or grey matter (GM) volumes remains to be determined. METHODS:
      Thirty patients with NMO, 30 healthy subjects matched for age and gender, 21
      patients with multiple sclerosis (MS) and 20 patients with a clinically isolated
      syndrome (CIS) were studied. We applied a SIENAX post-treatment software. We
      compared white matter (WM) and GM volumes between groups and explored
      correlations of changes in NMO patients with age, gender, duration, disease
      severity, visual acuity and T2 hyperintensities. We also performed a voxel-based
      morphometry (VBM) analysis to identify the regions affected by loss of volume.
      RESULTS: White matter volume was significantly reduced in patients with NMO
      (764.4 +/- 58.3 cm(3) ) compared to healthy subjects (843.1 +/- 49.3 cm(3) ) (P <
      0.001), whereas no difference was observed for the GM. Patients with CIS also
      presented an elective atrophy of WM and MS an atrophy of both WM and GM. We did
      not find any predictive factors of brain atrophy. The decrease in WM volume in
      NMO was noted even in the absence of visible MRI hypersignals. The VBM analysis
      found a few regions of WM atrophy (corpus callosum and optic radiations, P <
      0.005, uncorrected) and a few regions of GM atrophy (thalamus and prefrontal
      cortex, P < 0.001, uncorrected). CONCLUSION: These results suggest a significant
      brain involvement in NMO, especially an involvement of WM which appears not to be
      limited to secondary degeneration after spinal cord and optic nerve damage.

PMID- 22978569
TI  - Palladium-catalyzed C-H activation taken to the limit. Flattening an aromatic
      bowl by total arylation.
AB  - All 10 C-H positions on the rim of corannulene can be arylated by repetitive
      palladium-catalyzed C-H activation. To relieve congestion among the 10 tightly
      packed aryl substituents in the product, the central corannulene adopts a nearly
      planar geometry.

PMID- 22978570
TI  - Real-time molecular imaging throughout the entire cell cycle by targeted
      plasmonic-enhanced Rayleigh/Raman spectroscopy.
AB  - Due to their strong enhancement of scattered light, plasmonic nanoparticles have
      been utilized for various biological and medical applications. Here, we describe
      a new technique, Targeted Plasmonic-Enhanced Single-Cell Rayleigh/Raman
      Spectroscopy, to monitor the molecular changes of any cell-component, such as the
      nucleus, during the different phases of its full cell cycle by simultaneously
      recording its Rayleigh images and Raman vibration spectra in real-time. The
      analysis of the observed Raman DNA and protein peaks allowed the different phases
      of the cell cycle to be identified. This technique could be used for disease
      diagnostics and potentially improve our understanding of the molecular mechanisms
      of cellular functions such as division, death, signaling, and drug action.

PMID- 22978571
TI  - Moderate deacylation efficiency of DacD explains its ability to partially restore
      beta-lactam resistance in Escherichia coli PBP5 mutant.
AB  - Of the five dd-carboxypeptidases in Escherichia coli, only PBP5 demonstrates its
      physiological significance by maintaining cell shape and intrinsic beta-lactam
      resistance. DacD can partially compensate for the lost beta-lactam resistance in
      PBP5 mutant, although its biochemical reason is unclear. To understand the
      mechanism(s) underlying such behaviour, we constructed soluble DacD (sDacD) and
      compared its biophysical and biochemical properties with those of sPBP5, in
      vitro. Unlike sPBP6, sDacD can deacylate Bocillin significantly, which is very
      similar to sPBP5. sDacD shows weak dd-carboxypeptidase activity, although lower
      than that of sPBP5. Bioinformatics analyses reveal a similar architecture of
      sPBP5 and sDacD. Therefore, based on the obtained results we can infer that
      biochemically DacD and PBP5 are more closely related to each other than to PBP6,
      enabling DacD and PBP5 to play a nearly similar physiological function in terms
      of recovering the lost beta-lactam resistance.

PMID- 22978572
TI  - Empirical analysis shows reduced cost data collection may be an efficient method
      in economic clinical trials.
AB  - BACKGROUND: Data collection for economic evaluation alongside clinical trials is
      burdensome and cost-intensive. Limiting both the frequency of data collection and
      recall periods can solve the problem. As a consequence, gaps in survey periods
      arise and must be filled appropriately. The aims of our study are to assess the
      validity of incomplete cost data collection and define suitable resource
      categories. METHODS: In the randomised KORINNA study, cost data from 234 elderly
      patients were collected quarterly over a 1-year period. Different strategies for
      incomplete data collection were compared with complete data collection. The
      sample size calculation was modified in response to elasticity of variance.
      RESULTS: Resource categories suitable for incomplete data collection were
      physiotherapy, ambulatory clinic in hospital, medication, consultations,
      outpatient nursing service and paid household help. Cost estimation from complete
      and incomplete data collection showed no difference when omitting information
      from one quarter. When omitting information from two quarters, costs were
      underestimated by 3.9% to 4.6%.With respect to the observed increased standard
      deviation, a larger sample size would be required, increased by 3%. Nevertheless,
      more time was saved than extra time would be required for additional patients.
      CONCLUSION: Cost data can be collected efficiently by reducing the frequency of
      data collection. This can be achieved by incomplete data collection for shortened
      periods or complete data collection by extending recall windows. In our analysis,
      cost estimates per year for ambulatory healthcare and non-healthcare services in
      terms of three data collections was as valid and accurate as a four complete data
      collections. In contrast, data on hospitalisation, rehabilitation stays and care
      insurance benefits should be collected for the entire target period, using
      extended recall windows. When applying the method of incomplete data collection,
      sample size calculation has to be modified because of the increased standard
      deviation. This approach is suitable to enable economic evaluation with lower
      costs to both study participants and investigators. TRIAL REGISTRATION: The trial
      registration number is ISRCTN02893746.

PMID- 22978573
TI  - Sdf-1 (CXCL12) improves skeletal muscle regeneration via the mobilisation of
      Cxcr4 and CD34 expressing cells.
AB  - BACKGROUND INFORMATION: The regeneration of skeletal muscles involves satellite
      cells, which are muscle-specific precursor cells. In muscles, injured either
      mechanically or as a consequence of a disease, such as muscular dystrophy, local
      release of the growth factors and cytokines leads to satellite cells activation,
      proliferation and differentiation of the resulting myoblasts, followed by the
      formation of new myofibres. Various cell types, such as stem and progenitor
      cells, originating from other tissues different than the muscle, are also able to
      follow a myogenic program. Participation of these cells in the repair process
      depends on their precise mobilisation to the site of the injury. RESULTS: In this
      study, we showed that stromal-derived factor-1 (Sdf-1) impacts on the
      mobilisation of CXC chemokine receptor (Cxcr)4-positive cells and improves
      skeletal muscle regeneration. Analysis of isolated and in vitro cultured
      satellite cells showed that Sdf-1 did not influence myoblasts proliferation and
      expression of myogenic regulatory transcription factors but induced migration of
      the myoblasts in Cxcr4-dependent ways. This phenomenon was also associated with
      the increased activity of crucial extracellular matrix modifiers, i.e.
      metalloproteases Mmp-2 and Mmp-9. CONCLUSIONS: Thus, positive impact of Sdf-1 on
      muscle regeneration is related to the mobilisation of endogenous cells, that is
      satellite cells and myoblasts, as well as non-muscle stem cells, expressing Cxcr4
      and CD34.

PMID- 22978574
TI  - Computational analysis of lung deformation after murine pneumonectomy.
      [corrected].
AB  - In many mammalian species, the removal of one lung (pneumonectomy) is associated
      with the compensatory growth of the remaining lung. To investigate the hypothesis
      that parenchymal deformation may trigger lung regeneration, we used microCT
      scanning to create 3D finite element geometric models of the murine lung pre- and
      post-pneumonectomy (24 h). The structural correspondence between models was
      established using anatomic landmarks and an iterative computational algorithm.
      When compared with the pre-pneumonectomy lung, the post-pneumonectomy models
      demonstrated significant translation and rotation of the cardiac lobe into the
      post-pneumonectomy pleural space. 2D maps of lung deformation demonstrated
      significant heterogeneity; the areas of greatest deformation were present in the
      subpleural regions of the lobe. Consistent with the previously identified growth
      patterns, subpleural regions of enhanced deformation are compatible with a
      mechanical signal - likely involving parenchymal stretch - triggering lung
      growth. 

PMID- 22978575
TI  - Dietetic research impact and influence: the power of strong coalitions.

PMID- 22978578
TI  - Superhydrophobic and adhesive properties of surfaces: testing the quality by an
      elaborated scanning electron microscopy method.
AB  - In contrast to advancements in the fabrication of new superhydrophobic materials,
      the characterization of their water repellency and quality is often coarse and
      unsatisfactory. In view of the problems and inaccuracies, particularly in the
      measurement of very high contact angles, we developed alternative methods for the
      characterization of superhydrophobic surfaces. It was found that adhering water
      remnants after immersion are a useful criterion in determining the repellency
      quality. In this study, we introduce microscopy methods to detect traces of water
      resembling test liquids on superhydrophobic surfaces by scanning electron
      microscopy (SEM) or fluorescence light microscopy (FLM). Diverse plant surfaces
      and some artificial superhydrophobic samples were examined. Instead of pure
      water, we used aqueous solutions containing a detectable stain and glycerol in
      order to prevent immediate evaporation of the microdroplets. For the SEM
      examinations, aqueous solutions of lead acetate were used, which could be
      detected in a frozen state at -90  degrees C with high sensitivity using a
      backscattered electron detector. For fluorescence microscopy, aqueous solutions
      of auramine were used. On different species of superhydrophobic plants, varying
      patterns of remaining microdroplets were found on their leaves. On some species,
      drop remnants occurred only on surface defects such as damaged epicuticular
      waxes. On others, microdroplets regularly decorated the locations of increased
      adhesion, particularly on hierarchically structured surfaces. Furthermore, it is
      demonstrated that the method is suitable for testing the limits of repellency
      under harsh conditions, such as drop impact or long-enduring contact. The
      supplementation of the visualization method by the measurement of the pull-off
      force between a water drop and the sample allowed us to determine the adhesive
      properties of superhydrophobic surfaces quantitatively. The results were in good
      agreement with former studies of the water repellency and contact angles. In
      contrast to contact angle measurements, the acqusition of SEM images with high
      resolution and wide depth of sharpness gives better insight into the wetting
      behavior and susceptibility of the structural elements of the superhydrophobic
      surfaces.

PMID- 22978579
TI  - Bidirectional associations between insomnia symptoms and unhealthy behaviours.
AB  - It has been suggested that there are associations among insomnia symptoms and
      unhealthy behaviours. However, previous studies are sparse and mainly cross
      sectional, and have not been focused on several key unhealthy behaviours. The aim
      of this study was to examine whether the associations are bidirectional, i.e.
      whether insomnia symptoms are associated with subsequent unhealthy behaviours,
      and whether unhealthy behaviours are associated with subsequent insomnia
      symptoms. The data were derived from the Helsinki Health Study prospective cohort
      study. The baseline data were collected in 2000-02 (n = 8960, response rate 67%)
      among 40-60-year-old employees of the City Helsinki, Finland. The follow-up data
      were collected in 2007 (n = 7332, response rate 83%). Logistic regression
      analysis was used to examine the associations among insomnia symptoms and
      unhealthy behaviours, including smoking, heavy and binge drinking, physical
      inactivity and unhealthy food habits. Frequent insomnia symptoms at baseline were
      associated with subsequent heavy drinking [odds ratio (OR): 1.34; 95% confidence
      interval (CI): 1.07-1.68] and physical inactivity (OR: 1.27; 95% CI: 1.08-1.48)
      after full adjustment for gender, age, corresponding unhealthy behaviour at
      baseline, marital status, occupational class, sleep duration and common mental
      disorders. Additionally, heavy drinking (OR: 1.48; 95% CI: 1.22-1.80) and binge
      drinking (OR: 1.26; 95% CI: 1.08-1.46) at baseline were associated with
      subsequent insomnia symptoms at follow-up after full adjustment. In conclusion,
      insomnia symptoms were associated with subsequent heavy drinking and physical
      inactivity, and heavy and binge drinking were also associated with subsequent
      insomnia symptoms.

PMID- 22978580
TI  - Simple route to lattice energies in the presence of complex ions.
AB  - Lattice energies for ionic materials which separate into independent gaseous ions
      can be calculated by standard Born-Haber-Fajans thermochemical cycle procedures,
      based on the energies of formation of those ions. However, if complex ions (such
      as sulfates) occur in the material, then a sophisticated calculation procedure
      must be invoked which requires allocation of the total ion charge among the atom
      components of the complex ion and evaluation of the attractive and repulsive
      energy terms. If, instead, the total ion charge is allocated to the central atom
      of the complex ion (with zero charge on the coordinated atoms), to create a
      "condensed charge ion" (having zero self-energy), then a straightforward
      calculation of the electrostatic (Madelung) energy, E(M)', correlates well with
      published lattice energies: U(POT)/kJ mol(-1) = 0.963E(M)', with a correlation
      coefficient, R(2) = 0.976. E(M)' is here termed the "condensed charge"
      electrostatic (Madelung) energy. Thus, using the condensed charge ion model, we
      observe that a roughly constant proportion (~96%) of the corresponding lattice
      energy arises from the electrostatic interaction terms. The above equation
      permits ready evaluation of lattice energies for ionic crystal structures
      containing complex ions, without the necessity to estimate any of the problematic
      nonelectrostatic interaction terms. A commentary by Prof. H. D. B. Jenkins
      substantiating this analysis is appended.

PMID- 22978581
TI  - Refocusing on new priorities.

PMID- 22978582
TI  - Influence of 63Ser phosphorylation and dephosphorylation on the structure of the
      stathmin helical nucleation sequence: a molecular dynamics study.
AB  - Phosphorylation is an important mechanism regulating protein-protein interactions
      involving intrinsically disordered protein regions. Stathmin, an archetypical
      example of an intrinsically disordered protein, is a key regulator of microtubule
      dynamics in which phosphorylation of 63Ser within the helical nucleation sequence
      strongly down-regulates the tubulin binding and microtubule destabilizing
      activities of the protein. Experimental studies on a peptide encompassing the 19
      residue helical nucleation sequence of stathmin (residues 55-73) indicate that
      phosphorylation of 63Ser destabilizes the peptide's secondary structure by
      disrupting the salt bridges supporting its helical conformation. In order to
      investigate this hypothesis at atomic resolution, we performed molecular dynamics
      simulations of nonphosphorylated and phosphorylated stathmin-[55-73] at room
      temperature and pressure, neutral pH, and explicit solvation using the recently
      released GROMOS force field 54A7. In the simulations of nonphosphorylated
      stathmin-[55-73] emerged salt bridges associated with helical configurations. In
      the simulations of 63Ser phosphorylated stathmin-[55-73] these configurations
      dispersed and were replaced by a proliferation of salt bridges yielding
      disordered configurations. The transformation of the salt bridges was accompanied
      by emergence of numerous interactions between main and side chains, involving
      notably the oxygen atoms of the phosphorylated 63Ser. The loss of helical
      structure induced by phosphorylation is reversible, however, as a final
      simulation showed. The results extend the hypothesis of salt bridge derangement
      suggested by experimental observations of the stathmin nucleation sequence,
      providing new insights into regulation of intrinsically disordered protein
      systems mediated by phosphorylation.

PMID- 22978583
TI  - Histologically-validated footpad dermatitis scoring system for use in chicken
      processing plants.
AB  - 1. Footpad dermatitis (FPD) is a recognised welfare problem in broiler chickens.
      Broiler feet (n = 54) were examined macroscopically and microscopically to
      determine a reliable correspondence between macroscopic and histological
      features, and to devise a scoring system that was relevant to bird welfare and
      easy to use at processing plants. 2. Three types of footpad lesion were defined
      based on their severity. Type I were mild lesions, visually characterised by
      scale enlargement and erythema, and histologically by hyperplasia and
      hyperkeratosis of the epidermis, superficial dermal congestion and oedema. Type
      II were moderate, superficial lesions, visually characterised by hypertrophic and
      hyperkeratotic scales covered with yellowish to brownish exudate, and
      histologically by a prominent pustular and crust-forming dermatitis. Type III
      lesions were the most pronounced, visually characterised by a thick dark adherent
      crust, and histologically by extensive ulceration. 3. On the basis of the
      severity and extent of these three types of lesions, a 5-point scale was devised,
      i.e. no or type I lesion (score 1), type II lesion (<50% or >50% of footpad,
      scores 2 and 3 respectively) and type III lesion (<50% or >50% of footpad, scores
      4 and 5 respectively). 4. The scoring system has the advantage of making sense in
      terms of welfare compared with previous schemes. Furthermore, it is
      histologically validated and easy to use for the routine assessment of broiler
      welfare in processing plants.

PMID- 22978584
TI  - Performance of commercial laying hen genotypes on free range and organic farms in
      Switzerland, France and The Netherlands.
AB  - 1. A total of 257 farmers with free ranging laying hens (organic and
      conventional) in Switzerland, France and The Netherlands with 273 flocks were
      interviewed to determine the relationships between the genotype of the hens,
      management conditions and performance.   2. Almost 20 different genotypes
      (brands) were present on the farms. In France, all birds were brown feathered
      hens laying brown eggs. In Switzerland and The Netherlands, there were brown,
      white (white feathered hens laying white eggs) and silver (white feathered hens
      laying brown eggs) hens. In Switzerland, mixed flocks were also present.   3. The
      overall effect of system (organic vs. conventional free range) on egg production
      and mortality was significant, with higher mortality and lower egg production
      among organic hens. In pair wise comparisons within country, the difference was
      highly significant in The Netherlands, and showed a non-significant tendency in
      the same direction in Switzerland and France.   4. White hens tended to perform
      better than brown hens. Silver hens appeared to have a higher mortality and lower
      production per hen housed at 60 weeks of age.   5. There were no significant
      relationships between production, mortality, feather condition and use of outside
      run or with flock size.   6. There was more variation in mortality and egg
      production among farms with a small flock size than among farms with a large
      flock size.

PMID- 22978585
TI  - The use of conditioned place preference to determine broiler preferences for
      quantitative or qualitative dietary restriction.
AB  - 1. Calcium propionate (CAP) may improve the welfare of feed restricted broiler
      breeders by improving their satiety when included within the feed ration.
      However, the evidence for this is mixed. 2. This study used a closed economy
      conditioned place preference (CPP) task and aimed to identify whether broilers
      (as a model for broiler breeders) preferred an environment associated with
      quantitative food restriction (QFR) or an environment associated with a diet
      quality-adjusted by the inclusion of CAP. Birds taught to associate different
      environments with QFR and ad libitum (AL) access to feed were used to validate
      the methodology. 3. The two treatment groups were (1) QFR/AL (n = 12) in which
      birds alternated every 2 d between QFR and ad libitum access to food, and (2)
      QFR/CAP (n = 12) in which birds alternated every 2 d between QFR and QFR +
      calcium propionate (increased from 3-9% over the study period). Birds were taught
      to associate one diet option with vertical stripes and the other with horizontal
      black and white stripes. Each bird was tested twice for a CPP (once per diet). 4.
      QFR/AL birds showed a significant preference for the pen associated with ad
      libitum access to feed, but only when tested hungry (i.e. fed QFR on day of
      testing). QFR/CAP birds did not show a preference under either hunger state. 5.
      Reasons for the failure of QFR/CAP birds to show a preference are unclear but
      could include a lack of preference or failure to learn the task. 6. The existence
      of state-dependent effects indicates that care is needed in the design of future
      CPP studies and that the effect of calcium propionate and level of hunger on
      ability to learn a CPP needs further investigation.

PMID- 22978586
TI  - Anatomical and histological structure of the tongue and histochemical
      characteristics of the lingual salivary glands in the Chukar partridge (Alectoris
      chukar, Gray 1830).
AB  - 1. The aim of the study was to examine the morphology of the tongue and the
      histochemical features of the lingual salivary glands in this species.   2. The
      tongue was elongated, terminating in a rather sharp, dagger-like apex. On the
      surface of the tongue and situated between the body and root of the tongue, two
      rows of conical papillae, the sharp apices of which pointed towards the posterior
      part of the tongue, were observed. The keratinised epithelium lining the dorsal
      surface lacked typical gustatory papillae. However, it was observed that taste
      buds were present in the epithelium of the lingual body and root. The tongue was
      supported by a structure composed of hyaline cartilage, the paraglossum, which
      extended from the lingual root to the apex. Simple branched tubular glands, which
      were encapsulated by connective tissue, were embedded within the submucosa in the
      body (anterior salivary glands) and root (posterior salivary glands) of the
      tongue. It was observed that the secretion of the lingual glands contained
      neutral mucins, proteoglycans containing carboxylic acid, weak and strong
      sulphated groups, N-acetylated sialomucins, but lacked glycogen.   3. It was
      demonstrated that, the general morphological features, papillary distribution of
      the tongue and the histological structure of the mucosa epithelium and the
      supportive elements displayed similarity to those of other domestic avian
      species. It was also determined that, in view of the particular feeding types, in
      the partridge, the presence of the papillary crest was not correlated with diet.

PMID- 22978587
TI  - Genetic parameters for eggshell traits in ostriches.
AB  - 1. A study was conducted on ~14000 ostrich eggs to estimate genetic parameters
      for eggshell traits that could benefit the hatchability of ostrich eggs. Traits
      measured included the number of pores on the eggshell, the average diameter of
      these pores, the total area of pores on the eggshell, permeability (pore
      area/shell thickness) and eggshell thickness. 2. Heritability estimates ranged
      from 0.16 for total pore area to 0.41 for the natural logarithm of pore count.
      The heritability estimates for water loss on 21 and 35 d (WL21 and WL35) of
      incubation were high at 0.23 and 0.24, respectively. 3. On a genetic level, pore
      count was negatively correlated with average pore diameter (-0.73) and shell
      thickness (-0.28), whereas it was positively correlated with total pore area
      (0.58), WL21 (0.24) and WL35 (0.34). The direct and maternal genetic correlations
      of pore count with total pore area (0.58) and permeability (0.59) were high and
      significant. Permeability was positively correlated to WL21 and WL35, both on the
      direct and maternal genetic levels. 4. The estimated genetic parameters indicate
      that it should be possible to select for the various eggshell traits in ostrich
      eggs, or for permeability and water loss. However, as a trait with an
      intermediate optimum, direct selection for permeability and other eggshell traits
      would not be straightforward, and the possible application of these results to
      improve hatchability of ostrich eggs in the future needs consideration.

PMID- 22978588
TI  - Effects of dietary supplementation with a herbal extract on the performance of
      broilers infected with a mixture of Eimeria  species.
AB  - 1. A herbal extract containing a blend of three essential oils, derived from
      oregano, laurel leaf and lavender, was investigated as a feed additive
      alternative to the conventional anticoccidial sodium monensin.   2. Broilers were
      infected with a mixture of Eimeria species or left uninfected.   Both infected
      and uninfected broilers were provided with diets containing either herbal extract
      (HEX), monensin (MON) or without these supplements (CON). The HEX group had 50 mg
      herbal extract/kg diet and the MON group 100 mg monensin/kg diet.   3. All of the
      uninfected broilers exhibited higher body weight gain and better feed conversion
      when compared with their infected counterparts at d 28 and 42 of age. Both HEX
      and MON supplements caused significant improvements in performance in the
      infected broilers, but failed to have any effect on uninfected broilers.   4.
      Faecal oocyst output measured daily by sampling excreta, and expressed on a per
      bird basis, was lower in the HEX and MON groups than in the CON group. However,
      the herbal extract was not as effective as monensin in reducing oocyst excretion.
      Coccidial infection caused a significant increase in total intestinal length and
      caecal weight, but the dietary treatments did not influence these measurements.  
      5. These results indicate that providing a herbal extract in the diet was not as
      effective as monensin in protecting broilers exposed to a coccidial challenge.

PMID- 22978589
TI  - Extending the viability of emu spermatozoa during in vitro storage by
      manipulation of temperature and diluent potassium concentration.
AB  - 1. Survival of emu spermatozoa during in vitro storage is not affected by
      increasing the extracellular [K(+)] to the point where it does not adversely
      affect spermatozoa function. 2. In three experiments, the effects were studied of
      [K(+)] in a diluent in the range 12.5-80 mM/l on emu spermatozoa survival for up
      to 48 h at 5, 10 or 20 degrees C. 3. At the end of the storage period,
      spermatozoa viability, motility, fertilising ability and morphology were
      measured. 4. In Experiment 1, spermatozoa viability and morphology were adversely
      affected after storage (P < 0.001) only in the diluent containing 80 mM/l [K(+)]
      whereas spermatozoa motility decreased as [K(+)] increased from 12.5 to 80 mM/l.
      5. In Experiment 2, during storage at 5 degrees C, the spermatozoa viability was
      comparable among any of the diluents (standard or modified) but morphology was
      better (P < 0.001) in all of the modified diluents than in the standard E3
      diluent. 6. In Experiment 3, after 48 h of storage in a diluent containing 40
      mM/l of [K(+)], the spermatozoa functions were better preserved at 10 degrees C
      than at 5 or 20 degrees C. 7. It is concluded that a higher than physiological
      level of potassium can be used in a diluent without detrimental effect on emu
      spermatozoa survival during 48 h storage and that the best outcome was with
      storage at 10 degrees C rather than 5 or 20 degrees C.

PMID- 22978591
TI  - Characteristics of cold-induced dark, firm, dry broiler chicken breast meat.
AB  - 1. A study was designed to characterise dark, firm, dry (DFD) breast meat
      resulting from cold exposure of broilers and compare its properties with normal
      breast meat from cold-stressed and control birds. 2. A total of 140 broilers were
      selected from 5- and 6-week-old birds exposed to cold temperatures ranging from 
      18 to -4 degrees C, or a control temperature of +20 degrees C for 3 h in an
      environmental chamber. Half of these birds were slaughtered immediately following
      the cold exposure and the other half were given 2 h of lairage. 3. Breast meat
      samples were categorised based on ultimate pH (pH(u)) and colour L* (lightness)
      values into normal (5.7 <= pH(u)<= 6.1; 46 <= L* <= 53) breast meat from control
      (control-normal) or cold-stressed (cold-normal) birds, and DFD (pH(u) > 6.1; L* <
      46) breast meat, which only occurred in cold-stressed birds (cold-DFD). 4.
      Residual glycogen was not different between cold-DFD and control-normal breast
      meat. Lactate concentration was lower in cold-DFD compared with control-normal
      breast meat. Lactate concentration almost tripled for all the samples by 30 h
      post-mortem, which resulted in a drop in pH of normal meat, but did not have any
      effect on pH of DFD breast meat. Glycolytic potential at both 5 min and 30 h post
      mortem was lower in DFD breast meat compared with the normal breast meat from
      both cold-stressed and control birds. 5. Cold-DFD breast meat was significantly
      darker, with higher pH(u), lower cook loss, higher water-binding capacity and
      processing cook yield than cold-normal and control-normal breast meat, which were
      not different from each other.

PMID- 22978590
TI  - Structural and physical changes in the hen's eggshell in response to the
      inclusion of dietary organic minerals.
AB  - 1. An experiment was designed to determine whether the inclusion of sodium
      selenite, Sel-Plex or Sel-plex + Bioplex in the diet exerted any influence on
      structural and functional properties of the eggshell at 22, 38, 58 and 72 weeks
      age. 2. Significant age effects were demonstrated for egg weight, dynamic
      stiffness and total shell thickness. 3. The eggshells from birds fed on the Sel
      Plex + Bioplex treatment were statistically stronger than those produced by the
      birds on sodium selenite. 4. From mid-lay onwards the shells laid by birds fed on
      the Sel-Plex + Bioplex treatment displayed, at ultrastructural level, the crystal
      modification termed 'confluence' together with early fusion of the palisade
      columns which comprised the bulk of the shell. 5. At all periods of lay the
      shells of birds fed on sodium selenite, Sel-Plex and the control diet
      demonstrated the presence of a variety of crystalline aggregates localised
      between the forming palisade columns.

PMID- 22978592
TI  - Impact of a mixed chain length omega-3 fatty acid diet on production variables in
      commercial free-range laying hens.
AB  - 1. Previous studies found beneficial effects on the prevalence of keel fractures
      and bone health in laying hens receiving a short chain omega3 fatty acid diet.
      However, subsequent work using a mixed short and long chain omega3 diet (MCD)
      found little benefit to bone health and substantial production losses.   2. The
      current study examined commercial use of a mixed chain length ration in multiple
      farms and flocks and identified a detrimental effect on productivity including:
      mortality, number of poor quality eggs, hen daily average, feed consumption, and
      increased egg weight.   3. Production data were acquired from 11 flocks housed on
      5 farms and modelled using MlwiN, a statistical package developed for analysis of
      hierarchical data. Production responses were individually modelled with duration
      of exposure to the diet, age of introduction, flock size and farm, included as
      prediction variables.   4. Analysis indicated birds receiving the MCD manifested
      dramatic increases in mortality, poor quality eggs, mean egg weight, feed
      consumption and decreased production in comparison to control flocks receiving a
      standard ration. Increased exposure time appeared to increase the magnitude of
      the diet effect.   5. Although no data were collected to explain the potential
      mechanisms of this diet, the authors discuss several possible scenarios including
      excessive long chain omega3 content overwhelming eicosanoid regulatory capacity
      and changes in behaviour patterns.

PMID- 22978593
TI  - Serum and tissue concentrations of doxycycline in broilers after the sub
      cutaneous injection of a long-acting formulation.
AB  - 1. The antibacterial agent doxycycline hyclate (Dox) is usually administered to
      broilers in drinking water or as a feed supplement. Parenteral injection is not
      the usual route for administration, so a long-acting formulation (Dox-LA) was
      tested to evaluate if serum concentrations can achieve the
      pharmacokinetic/pharmacodynamic (PK/PD) ratios regarded as adequate for the drug.
      2. A poloxamer-based matrix was used to provide Dox-LA. Serum and tissue
      concentrations of Dox vs time were determined in two day-old broilers after
      subcutaneous (SC) injection of Dox-LA or oral administration of a single bolus of
      aqueous Dox (Dox-PO), at a dose of 20 mg/kg. Weight gain, feed conversion rate,
      haematological variables, aspartate aminotransferase and alanine aminotransferase
      activities, blood urea and creatinine were determined and compared for Dox-LA
      with Dox-PO and non-medicated controls. 3. Dox-LA had a high relative
      bioavailability (1200%). Maximum serum concentrations were not statistically
      different (5.1 +/- 1.1 ug/ml for Dox-LA and 6.1 +/- 1.4 ug/ml for Dox-PO), but
      half-life of Dox-LA was much greater than the value obtained for Dox-PO (73.0 +/-
      0.9 h and 2.0 +/- 0.02 h, respectively). Tissue concentrations were higher, and
      stayed higher for longer periods in the Dox-LA group. 4. In conclusion,
      considering the minimum effective serum concentration against Mycoplasma spp is
      0.5 ug/ml, a dose-interval of 180 h can be achieved with Dox-LA, but only for 24
      h after Dox-PO. Better PK/PD ratios for Dox-LA should result in improved clinical
      outcomes compared with Dox-PO.

PMID- 22978594
TI  - Pharmacokinetics and bioavailability of valnemulin in Muscovy ducks (Cairina
      moschata).
AB  - 1. A pharmacokinetic study of valnemulin was conducted in healthy Muscovy ducks
      after intravenous (IV), intramuscular (IM) and oral administrations at a dose
      rate of 15 mg/kg body weight. 2. Drug concentrations in plasma were determined by
      high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Pharmacokinetics parameters of valnemulin were analysed by compartmental analysis
      using the WinNonlin program. 3. After IV administration, valnemulin was widely
      distributed with a volume of distribution based on a terminal phase (V(z)) of
      8.19 +/- 3.07 l/kg, a mean elimination half-life (t(1/2Ke)) of 2.63 h, and a
      clearance (Cl) value of 5.56 +/- 1.53 l/kg/h. Following intramuscular and oral
      administration, valnemulin was rapidly absorbed; the C(max) was 0.44 +/- 0.13 and
      0.12 +/- 0.02 ug/ml (achieved at 0.28 and 1.80 h), the t(1/2Ke) was 3.17 +/- 3.83
      and 4.83 +/- 1.81 h, and the absolute bioavailability (F) was 72% and 37%,
      respectively. 4. The plasma profile of valnemulin exhibited favourable
      pharmacokinetic characteristics in Muscovy ducks, such as wide distribution, and
      rapid absorption and elimination, though oral bioavailability was low.

PMID- 22978595
TI  - The effects of turmeric supplementation on antioxidant status, blood gas indices
      and mortality in broiler chickens with T(3)-induced ascites.
AB  - 1. A total of 320 one-day-old Ross male broiler chickens were used to investigate
      the effects of 0.0, 2.5, 5.0 and 7.5 g/kg turmeric rhizome powder (TRP) in the
      diet, on antioxidant status, biochemical gas indices and mortality in broiler
      chickens with triiodothyronine (T(3)) induced ascites. 2. The TRP supplementation
      had no effect on blood pH, pO(2) or pCO(2) during the whole period of study.
      Moreover, supplementation of TRP did not influence the heart weight, right
      ventricle, left ventricle, or total ventricle weights, all relative to total live
      weight; RV/TV (right ventricle to total ventricle) ratio; or serum GPX
      (glutathione peroxidase) or SOD (superoxide dismutase) activities at week 6. 3.
      TRP supplementation influenced the blood [Formula: see text] and O(2) saturation
      during the whole period of study, total mortality due to ascites, and serum total
      tocopherol and malondialdehyde (MDA) contents. Blood [Formula: see text] and
      serum total tocopherol increased linearly as dietary TRP level increased. Blood
      O(2) saturation increased quadratically as dietary TRP increased. 4. Total
      ascites mortality and serum MDA content decreased linearly with increasing TRP
      level to 5 mg/kg and then reached a plateau. 5. The results of the study indicate
      that the addition of 5.0 g/kg TRP is sufficient to increase the blood O(2)
      saturation and bicarbonate ([Formula: see text]) concentration, and reduce the
      mortality due to ascites and serum MDA content.

PMID- 22978596
TI  - Changes in ovarian function and egg production in commercial broiler breeders
      through 40 weeks of lay.
AB  - 1. Egg production, body weight, feed intake and mortality were recorded in over
      78 000 broiler breeder hens in 4 commercial flocks housed in 16 houses from early
      lay though 40 weeks of lay. A total of 420 hens were sampled at regular intervals
      throughout the laying period to determine the changes in body weight and the
      numbers of yellow follicles, paired follicles and hierarchical positions with
      time in the ovary throughout lay to relate ovarian function to productivity.
      Average egg weight was recorded weekly from one flock. 2. A quadratic equation
      fitted the changes in time for the number of yellow follicles, body weight, feed
      intake and mortality; a linear equation described the decline in the number
      positions in the hierarchy and there was a linear decline in the logistic scale
      of the proportions of yellow follicles developing as pairs of similar weight. Egg
      production was described by a cubic equation and egg weight by a line plus
      exponential model. 3. The average number of yellow follicles declined from 7.2 to
      5.4 and the number of hierarchical positions from 6 to 5 from 4 to 40 weeks after
      photostimulation. The proportion of follicles developing as pairs of similar
      weight was over 25% at the onset of lay and declined to less than 10% from 20
      weeks after photostimulation, representing a substantial loss of potential
      productivity. 4. Body weight and egg production were similar to the breeder's
      targets whereas average egg weight and mortality were higher than expected. 5.
      The relationship defining ovarian function will facilitate the development of an
      improved model of egg production in broiler breeder hens.

PMID- 22978597
TI  - Efficiency of the cloacal sexing technique in greater rhea chicks (Rhea
      americana).
AB  - 1. The feasibility and accuracy of the cloacal sexing technique in greater rhea
      chicks was assessed using chicks of two captive populations of greater rhea in
      Cordoba, Argentina.   2. A total of 46 greater rhea chicks of 2 to 3 months of
      age were randomly arranged into three groups and the members of each group were
      sexed by a different operator.   3. A feather of each chick was plucked for
      sexing through a molecular method and results were used as controls.   4. Sex was
      correctly assigned by cloacal inspection in 98% of the cases. Chick manipulation
      was easily performed and no infections or traumatic lesions were observed a
      posteriori.   5. Cloacal sexing of rhea chicks up to 3 months of age does not
      affect animal welfare and should be considered an efficient alternative to
      molecular methods.

PMID- 22978598
TI  - Chicken dendritic cells and type II pneumocytes express a common intracellular
      epitope.
AB  - 1. CVI-ChNL 74.3, a dendritic cell-specific monoclonal antibody (mAb) also
      identifies chicken lung granular pneumocytes (type II pneumocytes), which produce
      surfactant.   2. The 74.3 mAb does not cross-react with any other avian or
      mammalian granular pneumocyte, and provides a convenient tool for monitoring the
      status of type II pneumocytes in the chicken lung.

PMID- 22978599
TI  - Sectarianism and the problem of overpopulation: political representations of
      reproduction in two low-income neighbourhoods of Beirut, Lebanon.
AB  - The role of confessionalism in the Lebanese healthcare sector, especially since
      the resolution of the Lebanese civil war (1975-1990), has yet to discussed at
      length in reproductive health research. Using biopolitical and structural
      violence models to describe how community leaders in two low-income
      neighbourhoods in Beirut describe reproductive healthcare - specifically through
      judgments of perceived sect size vis-a-vis perceived use of birth control
      measures - this paper attempts to provide critical analysis of the state of
      reproductive health in this setting. By using a theoretical model of analysis,
      which we refer to as the political anatomy of reproduction, we hope to unmask how
      confessionalism is perpetuated through discussions of reproductive health and how
      public health and medical communities can challenge this technique of power.

PMID- 22978600
TI  - Subendocardial increase in reactive oxygen species production affects regional
      contractile function in ischemic heart failure.
AB  - AIMS: Heart failure (HF) is characterized by regionalized contractile alterations
      resulting in loss of the transmural contractile gradient across the left
      ventricular free wall. We tested whether a regional alteration in mitochondrial
      oxidative metabolism during HF could affect myofilament function through protein
      kinase A (PKA) signaling. RESULTS: Twelve weeks after permanent left coronary
      artery ligation that induced myocardial infarction (MI), subendocardial (Endo)
      cardiomyocytes had decreased activity of complex I and IV of the mitochondrial
      electron transport chain and produced twice more superoxide anions than sham Endo
      and subepicardial cells. This effect was associated with a reduced antioxidant
      activity of superoxide dismutase and Catalase only in MI Endo cells. The
      myofilament contractile properties (Ca(2+) sensitivity and maximal tension),
      evaluated in skinned cardiomyocytes, were also reduced only in MI Endo myocytes.
      Conversely, in MI rats treated with the antioxidant N-acetylcysteine (NAC) for 4
      weeks, the generation of superoxide anions in Endo cardiomyocytes was normalized
      and the contractile properties of skinned cardiomyocytes restored. This effect
      was accompanied by improved in vivo contractility. The beneficial effects of NAC
      were mediated, at least, in part, through reduction of the PKA activity, which
      was higher in MI myofilaments, particularly, the PKA-mediated
      hyperphosphorylation of cardiac Troponin I. INNOVATION: The Transmural gradient
      in the mitochondrial content/activity is lost during HF and mediates reactive
      oxygen species-dependent contractile dysfunction. CONCLUSIONS: Regionalized
      alterations in redox signaling affect the contractile machinery of sub-Endo
      myocytes through a PKA-dependent pathway that contributes to the loss of the
      transmural contractile gradient and impairs global contractility.

PMID- 22978601
TI  - Multiscale macromolecular simulation: role of evolving ensembles.
AB  - Multiscale analysis provides an algorithm for the efficient simulation of
      macromolecular assemblies. This algorithm involves the coevolution of a
      quasiequilibrium probability density of atomic configurations and the Langevin
      dynamics of spatial coarse-grained variables denoted order parameters (OPs)
      characterizing nanoscale system features. In practice, implementation of the
      probability density involves the generation of constant OP ensembles of atomic
      configurations. Such ensembles are used to construct thermal forces and diffusion
      factors that mediate the stochastic OP dynamics. Generation of all-atom ensembles
      at every Langevin time step is computationally expensive. Here, multiscale
      computation for macromolecular systems is made more efficient by a method that
      self-consistently folds in ensembles of all-atom configurations constructed in an
      earlier step, history, of the Langevin evolution. This procedure accounts for the
      temporal evolution of these ensembles, accurately providing thermal forces and
      diffusions. It is shown that efficiency and accuracy of the OP-based simulations
      is increased via the integration of this historical information. Accuracy
      improves with the square root of the number of historical timesteps included in
      the calculation. As a result, CPU usage can be decreased by a factor of 3-8
      without loss of accuracy. The algorithm is implemented into our existing force
      field based multiscale simulation platform and demonstrated via the structural
      dynamics of viral capsomers.

PMID- 22978602
TI  - Oleoyl-L-carnitine inhibits glycine transport by GlyT2.
AB  - BACKGROUND AND PURPOSE: Concentrations of extracellular glycine in the CNS are
      regulated by two Na(+)/Cl(-) -dependent glycine transporters, GlyT1 and GlyT2.
      Selective inhibitors of GlyT1 have been developed for the treatment of
      schizophrenia, whilst selective inhibitors of GlyT2 are analgesic in animal
      models of pain. We have assessed a series of endogenous lipids as inhibitors of
      GlyT1 and GlyT2. EXPERIMENTAL APPROACH: Human GlyT1 and GlyT2 were expressed in
      Xenopus laevis oocytes, and the inhibitory actions of a series of acylcarnitines
      on glycine transport were measured using electrophysiological techniques. KEY
      RESULTS: Oleoyl-L-carnitine inhibited glycine transport by GlyT2, with an IC(50)
      of 340 nM, which is 15-fold more potent than the previously identified lipid
      inhibitor N-arachidonyl-glycine. Oleoyl-L-carnitine had a slow onset of
      inhibition and a slow washout. Using a series of chimeric GlyT1/2 transporters
      and point mutant transporters, we have identified an isoleucine residue in
      extracellular loop 4 of GlyT2 that conferred differences in sensitivity to oleoyl
      L-carnitine between GlyT2 and GlyT1. CONCLUSIONS AND IMPLICATIONS: Oleoyl-L
      carnitine is a potent non-competitive inhibitor of GlyT2. Previously identified
      GlyT2 inhibitors show potential as analgesics and the identification of oleoyl-L
      carnitine as a novel GlyT2 inhibitor may lead to new ways of treating pain.

PMID- 22978603
TI  - Male median raphe cysts: serial retrospective analysis and histopathological
      classification.
AB  - BACKGROUND: To review the clinical and pathological characteristics of median
      raphe cysts and to classify the lesions according to pathogenesis and
      histopathological findings. METHODS: The medical records of patients who were
      diagnosed with median raphe cysts between 2001 and 2010 were reviewed to document
      the clinical presentation and pathological findings of the cysts. RESULTS: Most
      patients were asymptomatic; however, 9 patients had inflammatory or infectious
      cysts that were tender or painful. Four patients who had cysts on the parameatus
      and distal prepuce had difficulty voiding. Hematuria and hematospermia were noted
      in 2 cases. Thirty-one cysts were lined with an urothelium-like epithelium, and a
      squamous epithelium lining was found in 3 cases. In 2 cases, a well-formed
      mucinous glandular structure was observed. The other 20 cysts consisted of mixed
      epithelia. After excision of the cysts under local or general anesthesia, an
      urethral fistula developed as a complication in only 1 case. CONCLUSIONS: Median
      raphe cysts are benign lesions formed due to tissue trapping during the
      development of urethral folds. The cysts can be defined into 4 types based on
      pathological findings: urethral, epidermoid, glandular, and mixed. The associated
      symptoms and signs should be taken into consideration when determining the
      treatment for the cysts. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here:
      http//http://www.diagnosticpathology.diagnomx.eu/vs/7727074877500751.

PMID- 22978604
TI  - Research-policy partnerships - experiences of the Mental Health and Poverty
      Project in Ghana, South Africa, Uganda and Zambia.
AB  - BACKGROUND: Partnerships are increasingly common in conducting research. However,
      there is little published evidence about processes in research-policy
      partnerships in different contexts. This paper contributes to filling this gap by
      analysing experiences of research-policy partnerships between Ministries of
      Health and research organisations for the implementation of the Mental Health and
      Poverty Project in Ghana, South Africa, Uganda and Zambia. METHODS: A conceptual
      framework for understanding and assessing research-policy partnerships was
      developed and guided this study. The data collection methods for this qualitative
      study included semi-structured interviews with Ministry of Health Partners
      (MOHPs) and Research Partners (RPs) in each country. RESULTS: The term
      partnership was perceived by the partners as a collaboration involving mutually
      agreed goals and objectives. The principles of trust, openness, equality and
      mutual respect were identified as constituting the core of partnerships. The
      MOHPs and RPs had clearly defined roles, with the MOHPs largely providing
      political support and RPs leading the research agenda. Different influences
      affected partnerships. At the individual level, personal relationships and
      ability to compromise within partnerships were seen as important. At the
      organisational level, the main influences included the degree of formalisation of
      roles and responsibilities and the internal structures and procedures affecting
      decision-making. At the contextual level, political environment and the degree of
      health system decentralisation affected partnerships. CONCLUSIONS: Several
      lessons can be learned from these experiences. Taking account of influences on
      the partnership at individual, organisation and contextual/system levels can
      increase its effectiveness. A common understanding of mutually-agreed goals and
      objectives of the partnership is essential. It is important to give attention to
      the processes of initiating and maintaining partnerships, based on clear roles,
      responsibilities and commitment of parties at different levels. Although
      partnerships are often established for a specific purpose, such as carrying out a
      particular project, the effects of partnership go beyond a particular initiative.

PMID- 22978605
TI  - Effect of linear elongation on carbon nanotube and polyelectrolyte structures in
      PDMS-supported nanocomposite LbL films.
AB  - Polyelectrolyte (PE) multilayer (PEM) thin films prepared by layer-by-layer self
      assembly on flexible substrates are exposed to elongation in many fields of
      technology. Upon elongation, these types of films are showing interesting, but
      not understood, phenomena, such as controlled wetting, stimuli-responsive
      nanovalves, and lithography-free surface structuring. To investigate the
      mechanisms causing these interesting phenomena, we employed spectroscopic
      investigations of supported PEM films that were prepared from polystyrene
      sulfonate (PSS)-wrapped single-walled carbon nanotubes (SWNTs) or pyrene-labeled
      PSS (PSS-PY) and polydiallyldiammonium chloride. Our results show that the SWNTs
      agglomerated upon deposition into the PEM and showed a strong change in
      orientation upon uniaxial elongation of the PEM. Upon release of elongation, the
      resulting wrinkling pattern was changing its wavelength upon time, in the case of
      the SWNT-containing PEM. Fluorescence measurements of the PSS-PY in the PEM
      showed that the PEs changed their orientation due to constant mechanical force
      from elongation up to a time scale of 2 days after beginning the elongation. The
      results prove that elongated and released PEM films, until now considered static
      structures, possess strong kinetics, which has to be taken into account for their
      application.

PMID- 22978607
TI  - Crossing the threshold: the power of multi-level experiments in identifying
      global change responses.

PMID- 22978606
TI  - Impact of a simulated oil spill on benthic phototrophs and nitrogen-fixing
      bacteria in mudflat mesocosms.
AB  - Coastal and estuarine ecosystems are highly susceptible to crude oil pollution.
      Therefore, in order to examine the resilience of benthic phototrophs that are
      pivotal to coastal ecosystem functioning, we simulated an oil spill in tidal
      mesocosms consisting of intact sediment cores from a mudflat at the mouth of the
      Colne Estuary, UK. At day 21, fluorescence imaging revealed a bloom of
      cyanobacteria on the surface of oiled sediment cores, and the upper 1.5 cm thick
      sediment had 7.2 times more cyanobacterial and 1.7 times more diatom rRNA
      sequences when treated with oil. Photosystem II operating efficiency (Fq'/Fm')
      was significantly reduced in oiled sediments at day 7, implying that the initial
      diatom-dominated community was negatively affected by oil, but this was no longer
      apparent by day 21. Oil addition significantly reduced numbers of the key deposit
      feeders, and the decreased grazing pressure is likely to be a major factor in the
      increased abundance of both diatoms and cyanobacteria. By day 5 concentrations of
      dissolved inorganic nitrogen were significantly lower in oiled mesocosms, likely
      resulting in the observed increase in nifH-containing, and therefore potentially
      dinitrogen-fixing, cyanobacteria. Thus, indirect effects of oil, rather than
      direct inhibition, are primarily responsible for altering the microphytobenthos.

PMID- 22978608
TI  - Climate change increases soil nitrous oxide emissions.

PMID- 22978609
TI  - Current 'relicts' more dynamic in history than previously thought.

PMID- 22978610
TI  - Fire futures for a megadiverse continent.

PMID- 22978611
TI  - Culturing a plant microbiome community at the cross-Rhodes.

PMID- 22978612
TI  - New research on plant-water relations examines the molecular, structural, and
      physiological mechanisms of plant responses to their environment.

PMID- 22978614
TI  - Super-resolution SERS imaging beyond the single-molecule limit: an isotope-edited
      approach.
AB  - Super-resolution imaging of single-molecule surface-enhanced Raman scattering (SM
      SERS) reveals a spatial relationship between the SERS emission centroid and the
      corresponding intensity. Here, an isotope-edited bianalyte approach is used to
      confirm that shifts in the SERS emission centroid are directly linked to the
      changing position of the molecule on the nanoparticle surface. By working above
      the single-molecule limit and exploiting SERS intensity fluctuations, the SERS
      centroid positions of individual molecules are found to be spatially distinct.

PMID- 22978613
TI  - The need to promote behaviour change at the cultural level: one factor explaining
      the limited impact of the MEMA kwa Vijana adolescent sexual health intervention
      in rural Tanzania. A process evaluation.
AB  - BACKGROUND: Few of the many behavioral sexual health interventions in Africa have
      been rigorously evaluated. Where biological outcomes have been measured,
      improvements have rarely been found. One of the most rigorous trials was of the
      multi-component MEMA kwa Vijana adolescent sexual health programme, which showed
      improvements in knowledge and reported attitudes and behaviour, but none in
      biological outcomes. This paper attempts to explain these outcomes by reviewing
      the process evaluation findings, particularly in terms of contextual factors.
      METHODS: A large-scale, primarily qualitative process evaluation based mainly on
      participant observation identified the principal contextual barriers and
      facilitators of behavioural change. RESULTS: The contextual barriers involved
      four interrelated socio-structural factors: culture (i.e. shared practices and
      systems of belief), economic circumstances, social status, and gender. At an
      individual level they appeared to operate through the constructs of the theories
      underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned
      Action - but the intervention was unable to substantially modify these individual
      level constructs, apart from knowledge. CONCLUSION: The process evaluation
      suggests that one important reason for this failure is that the intervention did
      not operate sufficiently at a structural level, particularly in regard to
      culture. Recently most structural interventions have focused on gender or/and
      economics. Complementing these with a cultural approach could address the belief
      systems that justify and perpetuate gender and economic inequalities, as well as
      other barriers to behaviour change.

PMID- 22978615
TI  - Effect of Diamel in patients with metabolic syndrome: a randomized double-blind
      placebo-controlled study.
AB  - BACKGROUND: The aim of the present study was to determine whether the
      administration of Diamel, marketed as a food supplement by Catalysis Laboratories
      (Madrid, Spain) could improve any of the components of metabolic syndrome (MS),
      as well as insulin resistance and sensitivity. METHODS: In all, 100 patients with
      MS (19-70 years of age) who satisfied the World Health Organization criteria for
      MS were included in the study. Participants were randomly assigned to receive
      either oral Diamel or a placebo (while maintaining a diet appropriate to their
      weight and physical activity) at a dose of two capsules before each of the three
      main meals each day for 1 year. Anthropometric indices, blood pressure, fasting
      plasma glucose, lipid profile, insulin, creatinine, and uric acid (UA) were
      determined. Insulin resistance (IR) was assessed and three indirect indices were
      used to calculate insulin sensitivity (IS). RESULTS: Compared with placebo,
      Diamel improved fasting insulin concentrations, IS, and IR and reduced UA
      concentrations from 6 months until the end of treatment (P < 0.05 for all). In
      addition, after 12 months treatment with Diamel, significant changes from
      baseline were seen for mean fasting insulin (P < 0.05), UA (P < 0.05), IR (P <
      0.001), and IS (P < 0.001), whereas no such changes were seen in the placebo
      treated group. Improvements were noted in body mass index, IR, and IS in both
      groups. CONCLUSIONS: Long-term Diamel treatment, combined with lifestyle changes,
      was beneficial for IR and IS, and reduced serum UA levels in patients with MS.

PMID- 22978617
TI  - Kinetics of enzyme action on surface-attached substrates: a practical guide to
      progress curve analysis in any kinetic situation.
AB  - In the present work, exact kinetic equations describing the action of an enzyme
      in solution on a substrate attached to a surface have been derived in the
      framework of the Michaelis-Menten mechanism but without resorting to the often
      used steady-state approximation. The here-derived kinetic equations are cast in a
      workable format, allowing us to introduce a simple and universal procedure for
      the quantitative analysis of enzyme surface kinetics that is valid for any
      kinetic situation. The results presented here should allow experimentalists
      studying the kinetics of enzyme action on immobilized substrates to analyze their
      data in a perfectly rigorous way.

PMID- 22978616
TI  - Computational identification of transcriptionally co-regulated genes, validation
      with the four ANT isoform genes.
AB  - BACKGROUND: The analysis of gene promoters is essential to understand the
      mechanisms of transcriptional regulation required under the effects of
      physiological processes, nutritional intake or pathologies. In higher eukaryotes,
      transcriptional regulation implies the recruitment of a set of regulatory
      proteins that bind on combinations of nucleotide motifs. We developed a
      computational analysis of promoter nucleotide sequences, to identify co-regulated
      genes by combining several programs that allowed us to build regulatory models
      and perform a crossed analysis on several databases. This strategy was tested on
      a set of four human genes encoding isoforms 1 to 4 of the mitochondrial ADP/ATP
      carrier ANT. Each isoform has a specific tissue expression profile linked to its
      role in cellular bioenergetics. RESULTS: From their promoter sequence and from
      the phylogenetic evolution of these ANT genes in mammals, we constructed
      combinations of specific regulatory elements. These models were screened using
      the full human genome and databases of promoter sequences from human and several
      other mammalian species. For each of transcriptionally regulated ANT1, 2 and 4
      genes, a set of co-regulated genes was identified and their over-expression was
      verified in microarray databases. CONCLUSIONS: Most of the identified genes
      encode proteins with a cellular function and specificity in agreement with those
      of the corresponding ANT isoform. Our in silico study shows that the tissue
      specific gene expression is mainly driven by promoter regulatory sequences
      located up to about a thousand base pairs upstream the transcription start site.
      Moreover, this computational strategy on the study of regulatory pathways should
      provide, along with transcriptomics and metabolomics, data to construct cellular
      metabolic networks.

PMID- 22978618
TI  - Translation of biomechanical concepts in bone tissue engineering: from animal
      study to revision knee arthroplasty.
AB  - Bone defects in revision knee arthroplasty are often located in load-bearing
      regions. The goal of this study was to determine whether a physiologic load could
      be used as an in situ osteogenic signal to the scaffolds filling the bone
      defects. In order to answer this question, we proposed a novel translation
      procedure having four steps: (1) determining the mechanical stimulus using finite
      element method, (2) designing an animal study to measure bone formation spatially
      and temporally using micro-CT imaging in the scaffold subjected to the estimated
      mechanical stimulus, (3) identifying bone formation parameters for the loaded and
      non-loaded cases appearing in a recently developed mathematical model for bone
      formation in the scaffold and (4) estimating the stiffness and the bone formation
      in the bone-scaffold construct. With this procedure, we estimated that after 3
      years mechanical stimulation increases the bone volume fraction and the stiffness
      of scaffold by 1.5- and 2.7-fold, respectively, compared to a non-loaded
      situation. 

PMID- 22978619
TI  - Gross umbilical cord complications are associated with placental lesions of
      circulatory stasis and fetal hypoxia.
AB  - Umbilical cord complications (UCC), such as true knots (TK), velamentous (VEL)
      insertion, marginal umbilical cord (MUC) insertion, umbilical cord entanglement
      (UCE) (both nuchal and non-nuchal), excessively long umbilical cord (ELUC), and
      excessively twisted umbilical cord (ETUC), can lead to decreased UC blood flow
      and have been associated with adverse fetal outcome and intrauterine fetal demise
      (IUFD). Few large series exist that correlate UCC with specific pathologic
      findings of the placenta. We present the largest series of UCC at this time.
      Eight hundred forty-one 3rd-trimester placentas with UCC were identified, as well
      as 858 randomly selected gestational age-matched placentas with grossly
      unremarkable UC. Lesions associated with circulatory stasis and thrombosis,
      including villous capillary congestion (VC), umbilical vessel distension (UVD),
      chorionic plate vessel distension (CPD), umbilical vessel thrombosis (UVT), fetal
      vascular thrombosis (FVT), intimal fibrin cushions (IFC), and avascular villi
      (AV), were noted, as well as other pathologic lesions. Data were analyzed by
      analysis of variance and Fisher exact tests, with P < 0.05 statistically
      significant. Umbilical cord complications as a group was associated with a
      significant increase in placental circulatory stasis lesions. Lesions associated
      with hypoxia, namely nucleated red blood cells and chorangiosis, were also
      increased. Finally, the presence of any UCC was significantly associated with
      IUFD. We also found that multiple UCC are associated with nonreassuring fetal
      heart rate and chorangiosis but that the presence of a single UCC was not. This
      indicates that UCC may lead to intrauterine hypoxia and subsequent adverse fetal
      outcome and that multiple UCC may be cumulative in effect.

PMID- 22978620
TI  - How do we talk to the children? Child life consultation to support the children
      of seriously ill adult inpatients.
AB  - BACKGROUND: Families with young children often struggle to talk about and cope
      with a parent's life-threatening illness and potential death. Adult
      interdisciplinary palliative medicine teams often feel unprepared to facilitate
      the open communication with these children that has been shown to reduce anxiety,
      depression, and other behavioral problems. In pediatric settings, child life
      specialists routinely provide this support to hospitalized children as well as
      their siblings and parents. Although these services are the standard of care in
      pediatrics, no research reports their use in the care of children of adults with
      serious illness. OBJECTIVE: Our aim is to describe a pilot child life
      consultation service for the children of seriously ill adult inpatients. DESIGN:
      We summarize the support needs of these children, their families, and the medical
      staff caring for them and report our experience with developing a child life
      consultation service to meet these needs. SETTING/SUBJECTS: Our service assists
      seriously ill adult inpatients and their families in a university medical center.
      RESULTS: Informal feedback from families and staff was uniformly positive. During
      consultations, family and child coping mechanisms were assessed and supported.
      Interventions were chosen to enhance the children's processing and self
      expression and to facilitate family communication. CONCLUSION: All hospitals
      should consider providing broad-based in-service training enabling their staff to
      improve the support they offer to the children of seriously ill parents. Medical
      centers with access to child life services should consider developing a child
      life consultation service to further enhance this support. More research is
      needed to evaluate both the short- and long-term clinical impact of these
      interventions.

PMID- 22978621
TI  - Dry micromanipulation of supramolecular giant vesicles on a silicon substrate:
      highly stable hydrogen-bond-directed nanosheet membrane.
AB  - Guanosine derivative 1 forms hydrogen-bond-directed giant vesicles. On a silicon
      substrate, the vesicles retain their shape and internal water phase even after
      removal of external water under vacuum. Dry manipulation of the micrometer-sized
      vesicles was carried out via AFM-tip-induced partition and fusion of the
      vesicles. For larger vesicles (5-10 MUm), external solutions were successfully
      injected through a microcapillary inserted into the vesicle in air.

PMID- 22978623
TI  - Composition of the archaeal community involved in methane production during the
      decomposition of  Microcystis  blooms in the laboratory.
AB  - We investigated the microbial processes involved in methane (CH(4)) production
      from  Microcystis  bloom scums at different temperatures. A Microcystis slurry
      was collected from Lake Taihu and incubated in airtight bottles at 15, 25, and 35
      degrees C. The production of CH(4) was monitored, and the emission rate was
      calculated. The dynamics of the methanogenic community were analyzed by terminal
      restriction fragment length polymorphism analysis of archaeal 16S rRNA genes.
      Phylogenetic information for the methanogens was obtained by cloning and
      sequencing selected samples. Significant CH(4) emission from the Microcystis
      scums was delayed by approximately 12 days by the natural oxygen depletion
      process, and CH(4) production was enhanced at higher temperatures. Phylogenetic
      analysis indicated that the archaeal community was composed of
      Methanomicrobiales, Methanobacteriaceae, and a novel cluster of Archaea. An
      apparent succession of the methanogenic community was demonstrated, with a
      predominance of Methanobacteriaceae at higher temperatures. Higher temperatures
      enhanced the methanogenic transformation of the Microcystis biomass and the
      phylogenetic dominance of hydrogenotrophic methanogens, suggesting that H(2) and
      CO(2) might be the primary substrates for CH(4) production during Microcystis
      decomposition without the participation of lake sediment. This work provides
      insight into the microbial components involved in Microcystis biomass
      fermentation in controlled systems.

PMID- 22978625
TI  - Alternating RBBB and LBBB post-AV node ablation: what is the mechanism?

PMID- 22978624
TI  - Experimental epilepsy affects Notch1 signalling and the stem cell pool in the
      dentate gyrus.
AB  - Temporal lobe epilepsy (TLE) is the most frequent form of epilepsy in adults. In
      addition to recurrent focal seizures, patients suffer from memory loss and
      depression. The factors contributing to these symptoms are unknown. In recent
      years, adult hippocampal neurogenesis has been implicated in certain aspects of
      learning and memory, as well as in depression and anhedonia. Here we investigated
      whether the adult hippocampal stem cell niche is affected by status epilepticus
      in a mouse model of TLE using unilateral intrahippocampal kainic acid injection.
      Eight days after status epilepticus, we found a strong diminution in Notch
      signalling, a key pathway involved in stem cell maintenance, as assayed by hes5
      reporter gene activity. In particular, hes5-GFP expression in the subgranular
      zone of the dentate gyrus was diminished. Furthermore, Sox2-positive cells as
      well as stem cell proliferation were reduced, thus pointing to a disruption of
      the stem cell niche in epilepsy under the present experimental conditions.

PMID- 22978627
TI  - Synthesis of chlorin-sensitized near infrared-emitting lanthanide complexes.
AB  - Lanthanide (Yb(3+), Nd(3+)) complexes equipped with red-absorbing hydroporphyrin
      (chlorin) antennae were synthesized and characterized. The syntheses are
      scalable, highly modular, and enable the introduction of different chlorins
      functionalized with a single reactive group (COOH or NH(2)). Absorption maxima
      were dependent on chlorin substitution pattern (monomeso aryl or dimeso aryl) and
      metalation state (free base or zinc chelate). The complexes benefit from dual
      chlorin (610-639 nm) and lanthanide (980 or 1065 nm for Yb- or Nd-complexes,
      respectively) emission in the biologically relevant red and near IR region of the
      spectrum.

PMID- 22978626
TI  - Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting
      effects of monoamine releasers in rats.
AB  - BACKGROUND AND PURPOSE: Monoamine releasers constitute a class of drugs that
      promote the release of dopamine (DA), serotonin (5-HT) and/or norepinephrine.
      Although some drugs in this class are well-known drugs of abuse (amphetamine,
      methamphetamine), others are thought to have reduced (3,4-methylenedioxy-N
      methylamphetamine [MDMA]) or no (fenfluramine) abuse potential. The purpose of
      this study was to further elucidate the role of dopamine versus serotonin
      selectivity on expression of abuse-related effects produced by monoamine
      releasers in an assay of intracranial self-stimulation (ICSS) in rats.
      EXPERIMENTAL APPROACH: This study evaluated effects produced in a frequency-rate
      ICSS procedure by 11 monoamine releasers that vary in selectivity to release DA
      versus 5-HT. KEY RESULTS: Efficacy of monoamine releasers to facilitate ICSS
      correlated with DA-selectivity, such that DA-selective releasers exclusively
      facilitated ICSS, a 5-HT-selective releaser exclusively depressed ICSS, and mixed
      action releasers both facilitated low ICSS rates and depressed high ICSS rates.
      Fixed-proportion mixtures of a DA-selective releaser and a 5-HT-selective
      releaser recapitulated effects of mixed-action releasers. Efficacy of monoamine
      releasers to facilitate ICSS also correlated with previously published data on
      efficacy to maintain self-administration in rhesus monkeys responding under a
      progressive-ratio schedule of reinforcement. CONCLUSIONS AND IMPLICATIONS: These
      data support the importance of selectivity for DA versus 5-HT in determining
      abuse potential of monoamine releasers and demonstrate a novel correlation
      between rat ICSS and nonhuman primate self-administration measures of abuse
      related effects. Taken together, these results support the use of ICSS in rats as
      an experimental tool to study the expression and pharmacological determinants of
      abuse-related effects of monoamine releasers.

PMID- 22978628
TI  - Trade-offs between leaf hydraulic capacity and drought vulnerability: morpho
      anatomical bases, carbon costs and ecological consequences.
AB  - Leaf hydraulic conductance (K(leaf) ) and vulnerability constrain plant
      productivity, but no clear trade-off between these fundamental functional traits
      has emerged in previous studies. We measured K(leaf) on a leaf area
      (K(leaf_area)) and mass basis (K(leaf_mass)) in six woody angiosperms, and
      compared these values with species' distribution and leaf tolerance to
      dehydration in terms of P(50), that is, the leaf water potential inducing 50%
      loss of K(leaf) . We also measured several morphological and anatomical traits
      associated with carbon investment in leaf construction and water transport
      efficiency. Clear relationships emerged between K(leaf_mass), P(50), and leaf
      mass per unit area (LMA), suggesting that increased tolerance to hydraulic
      dysfunction implies increased carbon costs for leaf construction and water use.
      Low P(50) values were associated with narrower and denser vein conduits,
      increased thickness of conduit walls, and increased vein density. This, in turn,
      was associated with reduced leaf surface area. Leaf P(50) was closely associated
      with plants' distribution over a narrow geographical range, suggesting that this
      parameter contributes to shaping vegetation features. Our data also highlight the
      carbon costs likely to be associated with increased leaf tolerance to hydraulic
      dysfunction, which confers on some species the ability to thrive under reduced
      water availability but decreases their competitiveness in high-resource habitats.

PMID- 22978629
TI  - Estimating the lifetime economic burden of Parkinson's disease in Singapore.
AB  - BACKGROUND AND PURPOSE: We aimed to estimate the lifetime cost of Parkinson's
      disease (PD) from the societal perspective. METHODS: A convenience sample of
      English or Chinese-speaking patients with PD was recruited from a PD and Movement
      Disorders Centre in Singapore to complete a financial burden questionnaire.
      Sociodemographic and clinical data were retrieved from hospital databases. Markov
      cohort model analysis was performed (cycle length, 1-year; duration, death or
      reached 100 years old). Patients were assumed to progress from one Markov state
      to the next state or death without skipping states or regressing. All model
      parameters were based on published local data. RESULTS: In 195 patients with PD
      (median age: 68.9, male: 51.8%), the simulated lifetime cost of PD was Singapore
      Dollar (SGD) 60,487 (EUR purchasing power parity 56,253) per patient. Direct
      medical, non-medical and indirect cost accounted for 18.8%, 12.8% and 68.4% of
      total lifetime cost, respectively. The top three components of total lifetime
      cost were productivity losses (67.6%), pharmacotherapy (11.4%) and home care
      (8.7%). One-way sensitivity analysis and probabilistic sensitivity analyses
      revealed that estimates were sensitive to cost at H&Y stage 1, 2 and 2.5 and
      productivity losses. CONCLUSIONS: The lifetime cost of PD is evaluated for the
      first time. This cost is substantial and comparable to the lifetime cost of
      intracerebral haemorrhage in at least one study. Our study identified several
      priority areas for research and policy formulation: reducing productivity losses,
      reducing cost of pharmacotherapy, avoiding hospitalization and reducing home care
      cost.

PMID- 22978630
TI  - Addressing maternal healthcare through demand side financial incentives:
      experience of Janani Suraksha Yojana program in India.
AB  - BACKGROUND: Demand side financing (DSF) is a widely employed strategy to enhance
      utilization of healthcare. The impact of DSF on health care seeking in general
      and that of maternal care in particular is already known. Yet, its effect on
      financial access to care, out-of-pocket spending (OOPS) and provider motivations
      is not considerably established. Without such evidence, DSFs may not be
      recommendable to build up any sustainable healthcare delivery approach. This
      study explores the above aspects on India's Janani Suraksha Yojana (JSY) program.
      METHODS: This study employed design and was conducted in three districts of
      Orissa, selected through a three-stage stratified sampling. The quantitative
      method was used to review the Health Management Information System (HMIS). The
      qualitative methods included focus groups discussions with beneficiaries (n = 19)
      and community intermediaries (n = 9), and interviews (n = 7) with Ministry of
      Health officials. HMIS data enabled to review maternal healthcare utilization.
      Group discussions and interviews explored the perceived impact of JSY on in
      facility delivery, OOPS, healthcare costs, quality of care and performance
      motivation of community health workers. RESULTS: The number of institutional
      deliveries, ante-and post-natal care visits increased after the introduction of
      JSY with an annual net growth of 18.1%, 3.6% and 5% respectively. The financial
      incentive provided partial financial risk-protection as it could cover only 25.5%
      of the maternal healthcare cost of the beneficiaries in rural areas and 14.3% in
      urban areas. The incentive induced fresh out-of-pocket spending for some mothers
      and it could not address maternal care requirements comprehensively. An activity
      based community worker model was encouraging to augment maternal healthcare
      consumption. However, the existing level of financial incentives and systemic
      support were inadequate to motivate the volunteers optimally on their
      performance. CONCLUSION: Demand side financial incentive could enhance financial
      access to maternal healthcare. However, it did not adequately protect households
      from financial risks. An effective integration of JSY with similar social
      protection or financial risk-protection measures may protect mothers
      substantially from potential out-of-pocket spending. Further, this integrated
      approach may help upholding more awareness on maternal health rights and
      entitlements. It can also address maternal health beyond 'maternal healthcare'
      and ensure sustainability through pooled financial and non-financial resources.

PMID- 22978631
TI  - S-guanylation proteomics for redox-based mitochondrial signaling.
AB  - AIMS: 8-nitroguanosine 3',5'-cyclic monophosphate (8-Nitro-cGMP) is a nitrated
      derivative of cGMP that is formed via cross-talk of reactive oxygen species
      formed by NADPH oxidase 2 and mitochondria. This nitrated nucleotide can function
      as a unique electrophilic second messenger in regulation of redox signaling by
      inducing a post-translational modification of protein thiols via cGMP adduction
      (protein S-guanylation). With S-guanylation proteomics, we investigated
      endogenous mitochondrial protein S-guanylation. RESULTS: We developed a new mass
      spectrometry (MS)-based proteomic method-S-guanylation proteomics-which comprised
      two approaches: (i) direct protein digestion followed by immunoaffinity capture
      of S-guanylated peptides that were subjected to liquid chromatography-tandem MS
      (LC-MS/MS); and (ii) two-dimensional (2D)-gel electrophoretic separation of S
      guanylated proteins that were subjected to in-gel digestion, followed by LC
      MS/MS. We thereby identified certain mitochondrial proteins that are S-guanylated
      endogenously during immunological stimulation, including mortalin and 60-kDa heat
      shock protein (HSP60). Mortalin and HSP60 were recently reported to regulate
      mitochondrial permeability-transition pore (mPTP) opening, at least partly, by
      interacting with cyclophilin D, an mPTP component. Our data revealed that
      immunological stimulation and 8-nitro-cGMP treatment induced mPTP opening in a
      cyclophilin D-dependent manner. INNOVATION AND CONCLUSION: Our S-guanylation
      proteomic method determined that mitochondrial HSPs may be novel targets for
      redox modification via protein S-guanylation that participates in mPTP regulation
      and mitochondrial redox signaling.

PMID- 22978632
TI  - Evaluation of a multi-marker immunomagnetic enrichment assay for the
      quantification of circulating melanoma cells.
AB  - BACKGROUND: Circulating melanoma cells (CMCs) are thought to be valuable in
      improving measures of prognosis in melanoma patients and may be a useful marker
      of residual disease to identify non-metastatic patients requiring adjuvant
      therapy. We investigated whether immunomagnetic enrichment targeting multiple
      markers allows more efficient enrichment of CMCs from patient peripheral blood
      than targeting a single marker. Furthermore, we aimed to determine whether the
      number of CMCs in patient blood was associated with disease stage. METHODS: We
      captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well
      as the melanoma stem cell markers ABCB5 and CD271, both individually and in
      combination, by immunomagnetic enrichment. CMCs were enriched and quantified from
      the peripheral blood of 10 non-metastatic and 13 metastatic melanoma patients.
      RESULTS: Targeting all markers in combination resulted in the enrichment of more
      CMCs than when any individual marker was targeted (p < 0.001-0.028). Furthermore,
      when a combination of markers was targeted, a greater number of CMCs were
      enriched in metastatic patients compared with non-metastatic patients (p =
      0.007). CONCLUSIONS: Our results demonstrated that a combination of markers
      should be targeted for optimal isolation of CMCs. In addition, there are
      significantly more CMCs in metastatic patients compared with non-metastatic
      patients and therefore quantification of CMCs may prove to be a useful marker of
      disease progression.

PMID- 22978633
TI  - Modular unfolding and dissociation of the human respiratory syncytial virus
      phosphoprotein p and its interaction with the m(2-1) antiterminator: a singular
      tetramer-tetramer interface arrangement.
AB  - Paramyxoviruses share the essential RNA polymerase complex components, namely,
      the polymerase (L), phosphoprotein (P), and nucleoprotein (N). Human respiratory
      syncytial virus (RSV) P is the smallest polypeptide among the family, sharing a
      coiled coil tetramerization domain, which disruption renders the virus inactive.
      We show that unfolding of P displays a first transition with low cooperativity
      but substantial loss of alpha-helix content and accessibility to hydrophobic
      sites, indicative of loose chain packing and fluctuating tertiary structure,
      typical of molten globules. The lack of unfolding baseline indicates a native
      state in conformational exchange and metastable at 20  degrees C. The second
      transition starts from a true intermediate state, with only the tetramerization
      domain remaining folded. The tetramerization domain undergoes a two-state
      dissociation/unfolding reaction (37.3 kcal mol(-1)). The M(2-1) transcription
      antiterminator, unique to RSV and Metapneumovirus, forms a nonglobular P:M(2-1)
      complex with a 1:1 stoichiometry and a K(D) of 8.1 nM determined by fluorescence
      anisotropy, far from the strikingly coincident dissociation range of P and M(2-1)
      tetramers (10(-28) M(3)). The M(2-1) binding region has been previously mapped to
      the N-terminal module of P, strongly suggesting the latter as the metastable
      molten globule domain. Folding, oligomerization, and assembly events between
      proteins and with RNA are coupled in the RNA polymerase complex. Quantitative
      assessment of the hierarchy of these interactions and their mechanisms contribute
      to the general understanding of RNA replication and transcription in
      Paramyxoviruses. In particular, the unique P-M(2-1) interface present in RSV
      provides a valuable antiviral target for this worldwide spread human pathogen.

PMID- 22978634
TI  - Connecting, learning, leaving: supporting young parents in the community.
AB  - Providing support and parenting education through home visiting is a key early
      intervention strategy with young parents. Less is known about what home visitors
      do that makes a difference. The purpose of this paper is to describe the role and
      experiences of professional staff working with young parents participating in a
      multicomponent parent support programme (home visiting and supported parenting
      groups) provided by a non-government organisation in a socially disadvantaged
      area of Sydney, Australia. This was a qualitative descriptive study. Data were
      collected through three focus groups conducted with the same six staff over an 18
      month period. Participant descriptions of their role and experiences working with
      young mothers were analysed thematically. Additional data from 20 anonymised
      client records were analysed through content analysis. Analysis of the focus
      group data revealed two themes, 'Connecting' and 'Facilitating Learning'. The
      theme 'Connecting' reflected the development of a relationship with the young
      mother commencing with 'how do we engage them?', 'building trust' through to
      formation of a relationship described as 'they know we're not friends, they know
      we're workers'. The second theme, 'Facilitating Learning' was informed by the
      analysis of both group and client record data and comprised a number of themes
      around what and how mothers learnt, through to 'ending the relationship' as the
      mothers left the programme. The quality of a mothers' learning was dependent on
      the quality of the connection between herself and the staff, similarly their
      capacity and, or confidence to leave the programme was dependent on the
      relationship, 'connecting' and the learning undertaken. Role modelling through
      interactions with children as well as with each other was seen as the most
      effective way to facilitate social and parenting skill development, while formal
      education sessions were evaluated by the workers to be less successful than
      informal ones.

PMID- 22978635
TI  - Developing genomic resources for the common bottlenose dolphin (Tursiops
      truncatus): isolation and characterization of 153 single nucleotide polymorphisms
      and 53 genotyping assays.
AB  - Although single nucleotide polymorphisms (SNPs) are commonly used in human
      genetics, they have only recently been incorporated into genetic studies of non
      model organisms, including cetaceans. SNPs have several advantages over other
      molecular markers for studies of population genetics: they are quicker and more
      straightforward to score, cross-laboratory comparisons of data are less
      complicated, and they can be used successfully with low-quality DNA. We screened
      portions of the genome of one of the most abundant cetaceans in U.S. waters, the
      common bottlenose dolphin (Tursiops truncatus), and identified 153 SNPs resulting
      in an overall average of one SNP every 463 base pairs. Custom TaqMan((r))  Assays
      were designed for 53 of these SNPs, and their performance was tested by
      genotyping a set of bottlenose dolphin samples, including some with low-quality
      DNA. We found that in 19% of the loci examined, the minor allele frequency (MAF)
      estimated during initial SNP ascertainment using a DNA pool of 10 individuals
      differed significantly from the final MAF after genotyping over 100 individuals,
      suggesting caution when making inferences about MAF values based on small data
      sets. For two assays, we also characterized the basis for unusual clustering
      patterns to determine whether their data could still be utilized for further
      genetic studies. Overall results support the use of these SNPs for accurate
      analysis of both poor and good-quality DNA. We report the first SNP markers and
      genotyping assays for use in population and conservation genetic studies of
      bottlenose dolphins.

PMID- 22978636
TI  - Inflammatory angiomyolipoma of the liver: a rare hepatic tumor.
AB  - Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a
      varying heterogeneous mixture of three tissue components: blood vessels, smooth
      muscle and adipose cells. Hepatic AML may demonstrate a marked histological
      diversity. We herein present one case of hepatic AML exhibiting prominent
      inflammatory cells in the background, which happened in a 61-year-old Chinese
      female patient, without signs of tuberous sclerosis. Histologically, the striking
      feature was the infiltration of numerous inflammatory cells in the background,
      including small lymphocytes, plasma cells, and eosnophils. The tumor cells were
      spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and
      arranged along the vessels or scattered among the inflammatory background.
      Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick
      walled blood vessels were focally observed at the boundaries between the tumor
      and surrounding liver tissues. The tumor cells were positive immunostaining for
      HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be
      distinguished from other tumors with inflammatory background such as inflammatory
      myofibroblastic tumor and follicular dendritic cell tumor and deserves wider
      recognition for its occurrence as a primary hepatic tumor. Virtual slides: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370.

PMID- 22978637
TI  - Brain tissue oxygen monitoring after severe traumatic brain injury in children:
      relationship to outcome and association with other clinical parameters.
AB  - OBJECT: Minimizing secondary brain injuries after traumatic brain injury (TBI) in
      children is critical to maximizing neurological outcome. Brain tissue oxygenation
      monitoring (as measured by interstitial partial pressure of O2 [PbO2]) is a new
      tool that may aid in guiding therapies, yet experience in children is limited.
      This study aims to describe the authors' experience of PbO2 monitoring after TBI.
      It was hypothesized that PbO2 thresholds could be established that were
      associated with favorable neurological outcome, and it was determined whether any
      relationships between PbO2 and other important clinical variables existed.
      METHODS: Forty-six children with severe TBI (Glasgow coma scale score <= 8 after
      resuscitation) who underwent PbO2 and brain temperature monitoring between
      September 2004 and June 2008 were studied. All patients received standard
      neurocritical care, and 24 were concurrently enrolled in a trial of therapeutic
      early hypothermia (n = 12/group). The PbO2 was measured in the uninjured frontal
      cortex. Hourly recordings and calculated daily means of various variables
      including PbO2, intracranial pressure (ICP), cerebral perfusion pressure (CPP),
      mean arterial blood pressure, partial pressure of arterial O2, and fraction of
      inspired O2 were compared using several statistical approaches. Glasgow outcome
      scale scores were determined at 6 months after injury. RESULTS: The mean patient
      age was 9.4 years (range 0.1-16.5 years; 13 girls) and 8554 hours of monitoring
      were analyzed (PbO2 range 0.0-97.2 mm Hg). A PbO2 of 30 mm Hg was associated with
      the highest sensitivity/specificity for favorable neurological outcome at 6
      months after TBI, yet CPP was the only factor that was independently associated
      with favorable outcome. Surprisingly, instances of preserved PbO2 with altered
      ICP and CPP were observed in some children with unfavorable outcomes.
      CONCLUSIONS: Monitoring of PbO2 demonstrated complex interactions with clinical
      variables reflecting intracranial dynamics using this protocol. A higher
      threshold than reported in studies in adults was suggested as a potential
      therapeutic target, but this threshold was not associated with improved outcomes.
      Additional studies to assess the utility of PbO2 monitoring after TBI in children
      are needed.

PMID- 22978638
TI  - Dysplastic-reactive choroid plexus presenting as an intramedullary tumor of the
      cervicomedullary junction in a patient with myelomeningocele.
AB  - Dysplastic structural lesions within the fourth ventricle have been reported in
      patients with Chiari malformation type II (CM-II). The authors report the unique
      case of a 22-year-old patient with myelomeningocele who presented with
      progressive pain, decreasing hand function, and lower cranial nerve dysfunction
      in the context of a slowly enlarging intramedullary mass at the cervicomedullary
      junction. At surgery a multinodular mass attached to caudally displaced fourth
      ventricle choroid plexus was completely removed from an expanded central canal.
      The histopathological findings were consistent with dysplastic-reactive choroid
      plexus. Postoperatively the patient experienced relief of pain and improvement in
      hand strength. To the authors' knowledge, this is the first reported case in
      which dysplastic fourth ventricle choroid plexus was displaced caudally through
      the obex to become an intramedullary lesion at the cervicomedullary junction. Its
      subsequent slow enlargement with progressive neurological deficits may have been
      secondary to reactive inflammatory changes. For patients with myelomeningocele
      and CM-II, intramedullary dysplastic-reactive choroid plexus should be included
      in the differential diagnosis of mass lesions in this location.

PMID- 22978639
TI  - ReactionPredictor: prediction of complex chemical reactions at the mechanistic
      level using machine learning.
AB  - Proposing reasonable mechanisms and predicting the course of chemical reactions
      is important to the practice of organic chemistry. Approaches to reaction
      prediction have historically used obfuscating representations and manually
      encoded patterns or rules. Here we present ReactionPredictor, a machine learning
      approach to reaction prediction that models elementary, mechanistic reactions as
      interactions between approximate molecular orbitals (MOs). A training data set of
      productive reactions known to occur at reasonable rates and yields and verified
      by inclusion in the literature or textbooks is derived from an existing rule
      based system and expanded upon with manual curation from graduate level
      textbooks. Using this training data set of complex polar, hypervalent, radical,
      and pericyclic reactions, a two-stage machine learning prediction framework is
      trained and validated. In the first stage, filtering models trained at the level
      of individual MOs are used to reduce the space of possible reactions to consider.
      In the second stage, ranking models over the filtered space of possible reactions
      are used to order the reactions such that the productive reactions are the top
      ranked. The resulting model, ReactionPredictor, perfectly ranks polar reactions
      78.1% of the time and recovers all productive reactions 95.7% of the time when
      allowing for small numbers of errors. Pericyclic and radical reactions are
      perfectly ranked 85.8% and 77.0% of the time, respectively, rising to >93%
      recovery for both reaction types with a small number of allowed errors. Decisions
      about which of the polar, pericyclic, or radical reaction type ranking models to
      use can be made with >99% accuracy. Finally, for multistep reaction pathways, we
      implement the first mechanistic pathway predictor using constrained tree-search
      to discover a set of reasonable mechanistic steps from given reactants to given
      products. Webserver implementations of both the single step and pathway versions
      of ReactionPredictor are available via the chemoinformatics portal
      http://cdb.ics.uci.edu/.

PMID- 22978640
TI  - Synthesis of submicrometer hollow particles with a nanoscale double-layer shell
      structure.
AB  - The morphology of hollow, double-shelled submicrometer particles is generated
      through a rapid aerosol-based process. The inner shell is an essentially
      hydrophobic carbon layer of nanoscale dimension (20 nm), and the outer shell is a
      hydrophilic silica layer of approximately 40 nm, with the shell thickness being a
      function of the particle size. The particles are synthesized by exploiting
      concepts of salt bridging to lock in a surfactant (CTAB) and carbon precursors
      together with iron species in the interior of a droplet. This deliberate negation
      of surfactant templating allows a silica shell to form extremely rapidly, sealing
      in the organic species in the particle interior. Subsequent pyrolysis results in
      a buildup of internal pressure, forcing carbonaceous species against the silica
      wall to form an inner shell of carbon. The incorporation of magnetic iron oxide
      into the shells opens up applications in external stimuli-responsive
      nanomaterials.

PMID- 22978641
TI  - Core-shell compositional fine structures of dealloyed Pt(x)Ni(1-x) nanoparticles
      and their impact on oxygen reduction catalysis.
AB  - Using aberration-corrected scanning transmission electron microscopy and electron
      energy loss spectroscopy line profiles with Angstrom resolution, we uncover novel
      core-shell fine structures in a series of catalytically active dealloyed
      Pt(x)Ni(1-x) core-shell nanoparticles, showing the formation of unusual near
      surface Ni-enriched inner shells. The radial location and the composition of the
      Ni-enriched inner shells were sensitively dependent on the initial alloy
      compositions. We further discuss how these self-organized Ni-enriched inner
      shells play a key role in maintaining surface lattice strain and thus control the
      surface catalytic activity for oxygen reduction.

PMID- 22978643
TI  - Susceptibility to denaturation of caseins in milk samples for improving protein
      conformational study and their identification.
AB  - Caseins are phosphoproteins kept together by non-covalent interactions to form a
      highly stabilised dispersion in milk. This study intended to evaluate the
      different effects of denaturing solvents and solutions on caseins in order to
      optimise the chromatographic resolution for a better identification of individual
      casein fractions. The caseins were obtained from bovine skimmed milks by
      precipitation at pH 4.3, and the proteins were dissolved in water and three
      different solutions. The casein separation was performed by reversed-phase high
      performance liquid chromatography. Each casein was identified by matrix-assisted
      laser desorption ionisation-time-of-flight mass spectrometry. The best result was
      achieved by treating the caseins with solution D. 

PMID- 22978642
TI  - Whole transcriptome analysis of a reversible neurodegenerative process in
      Drosophila reveals potential neuroprotective genes.
AB  - BACKGROUND: Neurodegenerative diseases are progressive and irreversible and they
      can be initiated by mutations in specific genes. Spalt-like genes (Sall) encode
      transcription factors expressed in the central nervous system. In humans, SALL
      mutations are associated with hereditary syndromes characterized by mental
      retardation, sensorineural deafness and motoneuron problems, among others.
      Drosophila sall mutants exhibit severe neurodegeneration of the central nervous
      system at embryonic stage 16, which surprisingly reverts later in development at
      embryonic stage 17, suggesting a potential to recover from neurodegeneration. We
      hypothesize that this recovery is mediated by a reorganization of the
      transcriptome counteracting SALL lost. To identify genes associated to
      neurodegeneration and neuroprotection, we used mRNA-Seq to compare the
      transcriptome of Drosophila sall mutant and wild type embryos from
      neurodegeneration and reversal stages. RESULTS: Neurodegeneration stage is
      associated with transcriptional changes in 220 genes, of which only 5% were
      already described as relevant for neurodegeneration. Genes related to the groups
      of Redox, Lifespan/Aging and Mitochondrial diseases are significantly represented
      at this stage. By contrast, neurodegeneration reversal stage is associated with
      significant changes in 480 genes, including 424 not previously associated with
      neuroprotection. Immune response and Salt stress are the most represented groups
      at this stage. CONCLUSIONS: We identify new genes associated to neurodegeneration
      and neuroprotection by using an mRNA-Seq approach. The strong homology between
      Drosophila and human genes raises the possibility to unveil novel genes involved
      in neurodegeneration and neuroprotection also in humans.

PMID- 22978644
TI  - Rethinking data collection and signal processing. 1. Real-time oversampling
      filter for chemical measurements.
AB  - Minimizing noise in chemical measurements is critical to achieve low limits of
      detection and accurate measurements. We describe a real-time oversampling filter
      that offers a method to reduce stochastic noise in a time-dependent chemical
      measurement. The power of this technique is demonstrated in its application to
      the separation of dopamine and serotonin by micellar electrokinetic
      chromatography with amperometric detection. Signal-to-noise ratios were increased
      by almost an order of magnitude, allowing for limits of detection of 100 and 120
      amol, respectively. Real-time oversampling filters can be implemented using
      simple software algorithms and require no change to existing experimental
      apparatus. The application is not limited to analytical separations, and this
      technique can be used to improve the signal-to-noise ratio in any experiment
      where the necessary sampling rate is less than the maximum sampling rate of the
      analog-to-digital converter. Theory, implementation, and the performance of this
      filter are described. We propose that this technique should be the default mode
      of operation for an analog-to-digital converter.

PMID- 22978645
TI  - Retesting for latent tuberculosis in patients with inflammatory bowel disease
      treated with TNF-alpha inhibitors.
AB  - BACKGROUND: Patients treated with TNF-alpha inhibitors (TNFi) are at high risk of
      reactivation of latent tuberculosis (LTB). Prospective studies on monitoring of
      TB reactivation and/or infection in this risk group are lacking. AIM: To test the
      conversion and reversion rate of screening tests for latent TB serial tuberculin
      skin test (TST) and interferon-gamma release assay (IGRA) under ongoing TNFi
      therapy. METHODS: We retested consecutive patients with IBD receiving TNFi
      therapy for a minimum of 5 months for LTB using IGRA and TST. A detailed patient
      history and concomitant therapy were recorded for each subject. RESULTS: After a
      median of 34.9 weeks (20.7-177.7), IGRA was retested in 184/227 patients (81.1%;
      Crohn's disease n = 139, ulcerative colitis n = 45) still under index TNFi. TST
      was available in 144/184 subjects (78.2%). The majority of patients were TNFi
      naive (147/184, 79.9%). In a subgroup of patients who received isoniazid due to
      diagnosis of latent TB at baseline (n = 32), 6/13 patients (46.2%) with baseline
      positive IGRA and 3/22 patients (13.6%) with baseline positive TST reverted to
      negative at retesting. In patients without diagnosis of LTB at baseline no
      permanent IGRA conversion was observed, but there were 6/144 (4.2%) TST
      conversions from negative to positive. No single case of TB reactivation or
      infection was recorded during the observation period. CONCLUSIONS: During
      treatment TNF-alpha inhibitors conversion was observed for tuberculin skin test,
      but not interferon-gamma release assay. As compared with tuberculin skin test,
      interferon-gamma release assay reverted in nearly half of isoniazid-treated
      patients for latent tuberculosis. However, the fact that patients in whom the
      interferon-gamma release assay test result remained positive did not develop
      active tuberculosis during follow-up questions the utility of interferon-gamma
      release assay as a monitoring tool during chemoprevention.

PMID- 22978646
TI  - Foundation species influence trait-based community assembly.
AB  - Here, we incorporate facilitation into trait-based community assembly theory by
      testing two mutually compatible facilitative mechanisms: changes in the
      environmental filter, causing either an increase in the range of trait values
      (i.e. a range expansion effect) and/or a shift in trait distributions (i.e. a
      range shift effect); and changes in trait spacing, suggesting an effect on niche
      differentiation. We analyzed the distribution of three functional traits - leaf
      dry matter content, specific leaf area and lateral spread - of plant communities
      dominated by a cushion-forming foundation species at four sites differing in
      elevation and aspect. We found support for environmental filtering and niche
      differentiation mechanisms by cushions, with filtering effects (in particular
      range shifts) increasing with environmental severity at higher elevation. The
      effect size of cushions on trait distribution was similar to that of
      environmental gradients caused by elevation and aspect. The consideration of
      intraspecific trait variability improved the detection of cushion effects on
      trait distributions. Our results highlight the importance of facilitation in the
      modification of taxonomic and functional diversity of ecological communities, and
      indicate that facilitation can occur through combined effects on environmental
      filtering and niche differentiation, with strong environmental context dependence
      of each mechanism.

PMID- 22978647
TI  - Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the
      hereditary motor and sensory neuropathy-Russe in depth.
AB  - Four private mutations responsible for three forms demyelinating of Charcot-Marie
      Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been
      associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D
      (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene
      (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1
      gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a
      genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating
      CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and
      HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to
      investigate in depth the genetics and the associated clinical symptoms of this
      CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1
      g.9712G>C is a founder mutation, which arrived in Spain around the end of the
      18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder
      leading to severe weakness of the lower limbs and prominent distal sensory loss.
      Motor nerve conduction velocity was in the demyelinating or intermediate range.

PMID- 22978648
TI  - Histidine based fluorescence sensor detects Hg2+ in solution, paper strips, and
      in cells.
AB  - A chemosensor having a bipodal thiocarbamate scaffold attached to histidine
      moieties senses Hg(2+) with a remarkable selectivity. The binding results in a 50
      nm blue shift in the fluorescence spectra and a 19-fold enhancement of the
      fluorescence quantum yield of the ligand. In addition to the detection of Hg(2+)
      visually under UV light in solution, the chemosensor was used for fabrication of
      paper strips that detected Hg(2+) in aqueous samples. The sensor was also used
      for imaging Hg(2+) in adult zebrafish and in human epithelial carcinoma HeLa S3
      cells.

PMID- 22978649
TI  - A three-channel fluorescent probe that distinguishes peroxynitrite from
      hypochlorite.
AB  - A novel fluorescent probe for peroxynitrite, PN(600), was rationally designed on
      the basis of a unique fluorophore assembly approach. PN(600) is a green-emitting
      coumarin derivative. Upon oxidation by peroxynitrite, PN(600) is transformed into
      a highly fluorescent red-emitting resorufin derivative via an orange-emitting
      intermediate. This three-channel signaling capability enables PN(600) to
      differentiate peroxynitrite from other reactive oxygen and nitrogen species,
      including hypochlorite and hydroxyl radical. Moreover, PN(600) is membrane
      permeable and compatible with common TRITC filter sets and displays low
      cytotoxicity. Therefore, PN(600) is a promising candidate for in vitro
      peroxynitrite imaging.

PMID- 22978650
TI  - Hemagglutinating activity is directly correlated with colonization ability of
      shigellae in suckling mouse model.
AB  - The aim of the present study was to explore a new approach based on the
      hemagglutination (HA) assay to understand the colonization ability of  Shigella 
      spp. To study colonization ability, an animal model of 4-day-old suckling mouse,
      was exploited. We characterized the HA activity of 48 Shigella strains, with
      erythrocytes collected from rabbit, guinea pig, chicken, and sheep. Only rabbit
      and guinea pig erythrocytes showed positive HA reactions in most of the cases. On
      the basis of HA pattern, 4 strains from each serogroup were selected for in vivo
      colonization studies. Our results showed a positive correlation between HA
      activity and colonization ability of the strains belonging to different
      serogroups (groups A, B, C, and D) of Shigella. In all 4 serogroups, high HA
      titer was associated with greater intestinal colonization.

PMID- 22978651
TI  - Neurocircuitry for modeling drug effects.
AB  - The identification and functional understanding of the neurocircuitry that
      mediates alcohol and drug effects that are relevant for the development of
      addictive behavior is a fundamental challenge in addiction research. Here we
      introduce an assumption-free construction of a neurocircuitry that mediates acute
      and chronic drug effects on neurotransmitter dynamics that is solely based on
      rodent neuroanatomy. Two types of data were considered for constructing the
      neurocircuitry: (1) information on the cytoarchitecture and neurochemical
      connectivity of each brain region of interest obtained from different
      neuroanatomical techniques; (2) information on the functional relevance of each
      region of interest with respect to alcohol and drug effects. We used mathematical
      data mining and hierarchical clustering methods to achieve the highest standards
      in the preprocessing of these data. Using this approach, a dynamical network of
      high molecular and spatial resolution containing 19 brain regions and seven
      neurotransmitter systems was obtained. Further graph theoretical analysis
      suggests that the neurocircuitry is connected and cannot be separated into
      further components. Our analysis also reveals the existence of a principal core
      subcircuit comprised of nine brain regions: the prefrontal cortex, insular
      cortex, nucleus accumbens, hypothalamus, amygdala, thalamus, substantia nigra,
      ventral tegmental area and raphe nuclei. Finally, by means of algebraic criteria
      for synchronizability of the neurocircuitry, the suitability for in silico
      modeling of acute and chronic drug effects is indicated. Indeed, we introduced as
      an example a dynamical system for modeling the effects of acute ethanol
      administration in rats and obtained an increase in dopamine release in the
      nucleus accumbens-a hallmark of drug reinforcement-to an extent similar to that
      seen in numerous microdialysis studies. We conclude that the present
      neurocircuitry provides a structural and dynamical framework for large-scale
      mathematical models and will help to predict chronic drug effects on brain
      function.

PMID- 22978653
TI  - Phenotypes and clinical significance of circulating CD4(+)CD25(+) regulatory T
      cells (Tregs) in patients with acute-on-chronic liver failure (ACLF).
AB  - BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) play an important role in
      maintaining immunological tolerance to self and foreign antigens. T cell
      receptors (TCR) reflect the composition and function of T cells. It is not
      universally agreed that there is a relationship between CD4(+)CD25(+) Treg
      frequency and the severity of acute-on-chronic liver failure (ACLF). The
      repertoire of TCR beta chain variable (TCRBV) regions of peripheral Tregs in ACLF
      patients is not well understood. METHODS: Human PBMCs were separated and sorted
      into CD4(+)CD25(+) Treg subsets using density gradient centrifugation and
      magnetic activated cell sorting (MACS). The CD4(+)CD25(high) Treg frequency in
      peripheral blood of ACLF and chronic hepatitis B (CHB) patients was measured by
      flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene
      melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and
      sequenced when the GMSP profiles showed a single-peak. RESULTS: CD4(+)CD25(high)
      Treg prevalence in peripheral blood of ACLF patients is increased significantly
      compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The
      prevalence of CD4(+)CD25(high) Tregs in ACLF or CHB patients is positively
      correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most
      prevalent TCRBV in CD4(+)CD25(+) Tregs in ACLF and CHB patients. In addition, the
      CDR3 motifs were relatively conserved in these four TCRBV gene families.
      CONCLUSIONS: The CD4(+)CD25(high) Tregs prevalence in peripheral blood is
      indicative of disease severity in ACLF or CHB patients. The relatively conserved
      TCRBV20 CDR3 motif "TGTGHSPLH" and TCRBV11 CDR3 motif "VYNEQ" may be used in
      helping diagnosis and treat patients with ACLF.

PMID- 22978654
TI  - The equilibrium structure of lithium salt solutions in ether-functionalized
      ammonium ionic liquids.
AB  - Molecular dynamics simulations have been performed for ionic liquids based on a
      ternary mixture of lithium and ammonium cations and a common anion,
      bis(trifluoromethylsulfonyl)imide, [Tf(2)N](-). We address structural changes
      resulting from adding Li(+) in ionic liquids with increasing length of an ether
      functionalized chain in the ammonium cation. The calculation of static structure
      factors reveals the lithium effect on charge ordering and intermediate range
      order in comparison with the neat ionic liquids. The charge ordering is modified
      in the lithium solution because the coordination of [Tf(2)N](-) toward Li(+) is
      much stronger than ammonium cations. Intermediate range order is observed in neat
      ionic liquids based on ammonium cations with a long chain, but in the lithium
      solutions, there is also a nonhomogenous distribution of Li(+) cations. The
      presence of Li(+) enhances interactions between the ammonium cations due to
      correlations between the oxygen atom of the ether chain and the nitrogen atom of
      another ammonium cation.

PMID- 22978652
TI  - A small molecule inhibitor of Pot1 binding to telomeric DNA.
AB  - Chromosome ends are complex structures, consisting of repetitive DNA sequence
      terminating in an ssDNA overhang with many associated proteins. Because
      alteration of the regulation of these ends is a hallmark of cancer, telomeres and
      telomere maintenance have been prime drug targets. The universally conserved
      ssDNA overhang is sequence-specifically bound and regulated by Pot1 (protection
      of telomeres 1), and perturbation of Pot1 function has deleterious effects for
      proliferating cells. The specificity of the Pot1/ssDNA interaction and the key
      involvement of this protein in telomere maintenance have suggested directed
      inhibition of Pot1/ssDNA binding as an efficient means of disrupting telomere
      function. To explore this idea, we developed a high-throughput time-resolved
      fluorescence resonance energy transfer (TR-FRET) screen for inhibitors of
      Pot1/ssDNA interaction. We conducted this screen with the DNA-binding subdomain
      of Schizosaccharomyces pombe Pot1 (Pot1pN), which confers the vast majority of
      Pot1 sequence-specificity and is highly similar to the first domain of human Pot1
      (hPOT1). Screening a library of ~20 000 compounds yielded a single inhibitor,
      which we found interacted tightly with sub-micromolar affinity. Furthermore, this
      compound, subsequently identified as the bis-azo dye Congo red (CR), was able to
      competitively inhibit hPOT1 binding to telomeric DNA. Isothermal titration
      calorimetry and NMR chemical shift analysis suggest that CR interacts
      specifically with the ssDNA-binding cleft of Pot1, and that alteration of this
      surface disrupts CR binding. The identification of a specific inhibitor of ssDNA
      interaction establishes a new pathway for targeted telomere disruption.

PMID- 22978655
TI  - Neck/shoulder pain and low back pain among school teachers in China, prevalence
      and risk factors.
AB  - BACKGROUND: School teachers represent an occupational group among which there
      appears to be a high prevalence of neck and/or shoulder pain (NSP) and low back
      pain (LBP). Epidemiological data on NSP and LBP in Chinese teachers are limited.
      The aim of this study was to investigate the prevalence of and risk factors for
      NSP and LBP among primary, secondary and high school teachers. METHODS: In a
      cross-sectional study of teachers from 7 schools, information on participant
      demographics, work characteristics, occupational factors and musculoskeletal
      symptoms and pain were collected. RESULTS: Among 893 teachers, the prevalence of
      NSP and LBP was 48.7% and 45.6% respectively. There was significant association
      between the level and prevalence of NSP and LBP among teachers in different
      schools. The prevalence of NSP among female teachers was much higher than that
      for males. Self-reported NSP was associated with physical exercise (OR 0.55, 95%
      CI 0.35 to 0.86), prolonged standing (1.74, 1.03 to 2.95), sitting (1.76, 1.23 to
      2.52) and static posture (2.25, 1.56 to 3.24), and uncomfortable back support
      (1.77, 1.23 to 2.55). LBP was more consistently associated with twisting posture
      (1.93, 1.30 to 2.87), uncomfortable back support (1.62, 1.13 to 2.32) and
      prolonged sitting (1.42, 1.00 to 2.02) and static posture (1.60, 1.11 to 2.31).
      CONCLUSIONS: NSP and LBP are common among teachers. There were strong
      associations with different individual, ergonomic, and occupational factors.

PMID- 22978656
TI  - Pharmacologic rate versus rhythm-control strategies in atrial fibrillation: an
      updated comprehensive review and meta-analysis.
AB  - BACKGROUND: In patients with atrial fibrillation (AF), ventricular rate control
      with medications has been found to be noninferior in preventing clinical events,
      compared to a strategy converting patients to sinus rhythm and maintaining it
      with medications. Guidelines have accepted rate control as an acceptable
      therapeutic option. Most of the prior studies excluded patients without
      significant left ventricular dysfunction, or permanent AF. METHODS: The authors
      searched the PubMed, CENTRAL, and EMBASE databases for randomized controlled
      trials from 1966 to 2011. Trials included were direct head-to-head comparisons of
      rate- and rhythm-control strategy using pharmacological means. The primary
      outcome assessed was risk of all-cause mortality. We also assessed other pooled
      clinical endpoints using a random effects model (Mantel-Haenszel) between rate
      and rhythm-control strategies. RESULTS: Ten studies (total N = 7,867) met
      inclusion/exclusion criteria. In-hospital mortality was not different between
      groups (P = 0.31). The rates of stroke, systemic embolism, worsening heart
      failure, myocardial infarction, and bleeding were also similar. However, rates of
      rehospitalization were much lower with a rate-control strategy (P = 0.007). An
      exploratory analysis in patients younger than 65 years revealed a rhythm-control
      strategy was superior to rate control in the prevention of all-cause mortality (P
      = 0.0007). CONCLUSIONS: This systematic review suggests no difference in clinical
      outcomes with a rate or rhythm-control strategy with AF. However,
      rehospitalization rates appear to be lower with pharmacological rate control for
      all ages, while finding support for rhythm control in younger patients.

PMID- 22978657
TI  - bgc: Software for Bayesian estimation of genomic clines.
AB  - Introgression in admixed populations can be used to identify candidate loci that
      might underlie adaptation or reproductive isolation. The Bayesian genomic cline
      model provides a framework for quantifying variable introgression in admixed
      populations and identifying regions of the genome with extreme introgression that
      are potentially associated with variation in fitness. Here we describe the bgc
      software, which uses Markov chain Monte Carlo to estimate the joint posterior
      probability distribution of the parameters in the Bayesian genomic cline model
      and designate outlier loci. This software can be used with next-generation
      sequence data, accounts for uncertainty in genotypic state, and can incorporate
      information from linked loci on a genetic map. Output from the analysis is
      written to an HDF5 file for efficient storage and manipulation. This software is
      written in C++. The source code, software manual, compilation instructions and
      example data sets are available under the GNU Public License at
      http://sites.google.com/site/bgcsoftware/.

PMID- 22978658
TI  - Community pharmacist attitudes towards collaboration with general practitioners:
      development and validation of a measure and a model.
AB  - BACKGROUND: Community Pharmacists and General Practitioners (GPs) are
      increasingly being encouraged to adopt more collaborative approaches to health
      care delivery as collaboration in primary care has been shown to be effective in
      improving patient outcomes. However, little is known about pharmacist attitudes
      towards collaborating with their GP counterparts and variables that influence
      this interprofessional collaboration. This study aims to develop and validate 1)
      an instrument to measure pharmacist attitudes towards collaboration with GPs and
      2) a model that illustrates how pharmacist attitudes (and other variables)
      influence collaborative behaviour with GPs. METHODS: A questionnaire containing
      the newly developed "Attitudes Towards Collaboration Instrument for Pharmacists"
      (ATCI-P) and a previously validated behavioural measure "Frequency of
      Interprofessional Collaboration Instrument for Pharmacists" (FICI-P) was
      administered to a sample of 1215 Australian pharmacists. The ATCI-P was developed
      based on existing literature and qualitative interviews with GPs and community
      pharmacists. Principal Component Analysis was used to assess the structure of the
      ATCI-P and the Cronbach's alpha coefficient was used to assess the internal
      consistency of the instrument. Structural equation modelling was used to
      determine how pharmacist attitudes (as measured by the ATCI-P) and other
      variables, influence collaborative behaviour (as measured by the FICI-P).
      RESULTS: Four hundred and ninety-two surveys were completed and returned for a
      response rate of 40%. Principal Component Analysis revealed the ATCI-P consisted
      of two factors: 'interactional determinants' and 'practitioner determinants',
      both with good internal consistency (Cronbach's alpha = .90 and .93
      respectively). The model demonstrated adequate fit (chi2/df = 1.89, CFI = .955,
      RMSEA = .062, 90% CI [.049-.074]) and illustrated that 'interactional
      determinants' was the strongest predictor of collaboration and was in turn
      influenced by 'practitioner determinants'. The extent of the pharmacist's contact
      with physicians during their pre-registration training was also found to be a
      significant predictor of collaboration (B = .23, SE = .43, p <.001). CONCLUSIONS:
      The results of the study provide evidence for the validity of the ATCI-P in
      measuring pharmacist attitudes towards collaboration with GPs and support a model
      of collaboration, from the pharmacist's perspective, in which collaborative
      behaviour is influenced directly by 'interactional' and 'environmental
      determinants', and indirectly by 'practitioner determinants'.

PMID- 22978659
TI  - Brassica nigra plays a remedy role in hepatic and renal damage.
AB  - CONTEXT: Black mustard [Brassica nigra (L.) Koch] of the Brassicaceae
      (Cruciferae) family is commonly used as a spice and a cheap source of
      antimicrobial agents for bacterial infections. OBJECTIVES: The present
      investigation was to demonstrate the protective effect of the methanol extract of
      B. nigra leaves against D-galactosamine (D-GalN)-induced hepatic and
      nephrotoxicity in Wistar rats. METHODS: Activity of the methanol extract of B.
      nigra at doses of 200 and 400 mg/kg b.wt. against D-GalN (500 mg/kg b.wt.)
      induced toxicity, with silymarin used as the standard. Histological damage,
      activities of serum marker enzyme, hematological changes, metabolites such as
      bilirubin, urea, uric acid, and creatinine levels, tissue thiobarbutric acid
      reactive substance, enzymic and non-enzymic antioxidants and inflammatory marker
      enzymes such as myeloperoxidase, cathepsin D, and acid phosphatase were assessed.
      RESULTS: The D-GalN-induced toxicity was evident from a significant increase (p <
      0.001) in the serum and tissue inflammatory markers in toxic rats, when compared
      with the control (saline alone treated animals). The B. nigra pretreated groups
      (200 and 400 mg/kg b.wt.) showed significant (p < 0.001) reduction in the D-GalN
      induced toxicity as obvious from biochemical parameters. Histopathological
      observations confirm the protective effect of B. nigra leaf extract by reduction
      in hepatic and renal tissue damage. Experimentals extract showed a similar effect
      as the standard. CONCLUSIONS: The crude methanol extract of B. nigra leaf lacks
      inherent toxicity and exhibits hepatic and nephroprotective effects against D
      GalN-induced toxicity in Wistar rats.

PMID- 22978660
TI  - From single-strand breaks to double-strand breaks during S-phase: a new mode of
      action of the Escherichia coli Cytolethal Distending Toxin.
AB  - The Cytolethal Distending Toxin (CDT) is a genotoxin produced by several
      pathogenic bacteria. It is generally admitted that CDT induces double-strand
      breaks (DSB) and cell cycle arrest in G2/M-phase, in an ATM-dependent manner.
      Most of these results were obtained at high dose (over 1 MUg ml(-1) ) of CDT and
      late after treatment (8-24 h). We provide here evidence that the Escherichia coli
      CDT (EcCDT) - at low dose (50 pg ml(-1)  or LD50) and early after treatment (3-6
      h) - progressively induces DNA DSB, mostly in S-phase. DSB formation is related
      to the single-strand breaks induction by CDT, converted into DSB during the S
      phase. We also show that homologous recombination is mobilized to these S-phase
      associated DSB. This model unveils a new mechanism for CDT genotoxicity that may
      play a role in cells partly deficient in homologous recombination.

PMID- 22978661
TI  - Smoking restrictions on campus: changes and challenges at three Canadian
      universities, 1970-2010.
AB  - This article examines the restriction of smoking on university campuses in the
      Canadian context. Indoor smoking on campus is now completely prohibited by law,
      and universities are increasingly moving to restrict, or prohibit, outdoor
      smoking on their grounds. The research focuses on three case studies to identify
      changes in spatial restrictions on campus smoking over the last four decades
      (1970-2010), and to determine the challenges involved in establishing bans in
      outdoor areas of campus. The three universities were selected for their different
      approaches to the issue of outdoor smoking. Data collection involved semi
      structured interviews with 36 key informants, conducted from September 2010 to
      January 2011, supplemented by documentary information. Interview data were
      analysed thematically. Protection against environmental tobacco smoke (ETS) on
      campus proceeded incrementally, via policy-making at the provincial, municipal
      and institutional levels. Historically, institutional bans on indoor smoking were
      particularly significant, but their health benefits could be limited by the
      presence of private property on campus. Universities continue to initiate smoking
      restrictions today, with respect to outdoor bans. However, respondents reported
      myriad challenges in developing, implementing and maintaining such bans. Five
      principal concerns were articulated: the need for ongoing policy communication;
      management of community relations as smokers are displaced from campus;
      enforcement to ensure that the policy has practical effect; safety concerns; and
      difficulties relating to campus layout. Because challenges are diverse and
      contextual, effective protection against outdoor ETS on campus is likely to
      require an ongoing commitment on the part of administrators.

PMID- 22978662
TI  - A novel xylogenic suspension culture model for exploring lignification in
      Phyllostachys bamboo.
AB  - BACKGROUND: Some prominent cultured plant cell lines, such as the BY-2 cell line
      of tobacco (Nicotiana tabacum cv. 'Bright Yellow 2') and the T87 cell line of
      Arabidopsis (Arabidopsis thaliana L. Heynh., ecotype Columbia) are used as model
      plant cells. These suspension cell culture systems are highly applicable for
      investigating various aspects of plant cell biology. However, no such prominent
      cultured cell lines exist in bamboo species. RESULTS: We standardized a novel
      xylogenic suspension culture model in order to unveil the process of
      lignification in living bamboo cells. Initial signs of lignin deposition were
      able to be observed by a positive phloroglucinol-HCl reaction at day 3 to 5 under
      lignification conditions (LG), i.e., modified half-strength Murashige and Skoog
      medium (m1/2MS) containing 10 MUM 6-benzyladenine (BA) and 3% sucrose. Two types
      of xylogenic differentiation, both fiber-like elements (FLEs) with cell wall
      thickening and tracheary elements (TEs) with formation of perforations in the
      cell wall, were observed under these conditions. The suspension cells rapidly
      formed secondary cell wall components that were highly lignified, making up
      approximately 25% of the cells on a dry weight basis within 2 weeks. Detailed
      features involved in cell growth, differentiation and death during lignification
      were characterized by laser scanning microscopic imaging. Changes in transcript
      levels of xylogenesis-related genes were assessed by RT-PCR, which showed that
      the transcription of key genes like PAL1, C4H, CCoAOMT, and CCR was induced at
      day 4 under LG conditions. Furthermore, interunit linkage of lignins was compared
      between mature bamboo culms and xylogenic suspension cells by heteronuclear
      single quantum coherence (HSQC) NMR spectroscopy. The presence of the most common
      interunit linkages, including beta-aryl ether (beta-O-4), phenylcoumaran (beta-5)
      and resinol (beta-beta) structures was identified in the bamboo cultured cell
      lignin (BCCL) by HSQC NMR. In addition to these common features of lignin,
      several differences in lignin substructures were also found between the BCCL and
      the bamboo milled wood lignin (BMWL). CONCLUSIONS: Our xylogenic suspension
      culture model could be used for detailed characterization of physiological and
      molecular biological events in living bamboo cells.

PMID- 22978664
TI  - Construction of naphtho-fused oxindoles via the aryne Diels-Alder reaction with
      methyleneindolinones.
AB  - Unprecedented aryne Diels-Alder reactions by using methyleneindolinones as dienes
      have been disclosed, thus providing a quick access to unusual naphtho-fused
      oxindoles. A wide range of methyleneindolinones proceed readily with arynes to
      afford the functionalized oxindoles in good yields.

PMID- 22978663
TI  - Aldose reductase inhibition prevents colon cancer growth by restoring phosphatase
      and tensin homolog through modulation of miR-21 and FOXO3a.
AB  - AIMS: We have shown earlier that inhibition of aldose reductase (AR), an
      oxidative stress-response protein, prevents colon cancer cell growth in vitro and
      in vivo. Changes in microribonucleic acid (miR) expression can contribute to
      cancer by modulating the functional expression of critical genes involved in
      cancer growth and metastasis. However, the molecular mechanisms by which AR
      regulates miR expression and their dependent mitogenic effects in cancer cells
      are not known. Therefore, we investigated how AR regulates growth factor-induced
      expression of miRs and growth of colon cancer cells. RESULTS: Inhibition of AR
      significantly downregulated growth factor-induced miR-21 expression in human
      colon cancer cells, HT29, SW480, and Caco-2. Further, AR inhibition also
      increased phosphatase and tensin homolog (PTEN) (a direct target of miR-21) and
      forkhead box O3A (FOXO3a) in colon cancer cells. Our results obtained with HT29
      cells ablated with FOXO3a siRNA showed increased activator protein-1 (AP-1)
      activation and miR-21 expression, indicating that FOXO3a represses miR-21 via AP
      1 inactivation. Inhibition of AR also prevented the epidermal growth factor
      induced phosphorylation of phosphatidylinositol 3-kinase (PI3K), serine/threonine
      kinase (AKT), c-Jun, c-Fos, PTEN, and FOXO3a, and deoxyribonucleic acid (DNA)
      binding activity of AP-1. More importantly, in human colon adenocarcinoma
      xenograft tissues, miR-21 expression was lower, and PTEN and FOXO3a levels were
      significantly higher in AR inhibitor-treated mice compared to controls.
      INNOVATION: These findings demonstrate a novel role of AR in the regulation of
      miR-21 and its target PTEN in growth factor-induced colon cancer cell growth.
      CONCLUSIONS: Collectively, these results show a novel role of AR in mediation of
      growth factor-induced colon cancer growth by modulating miR-21, PTEN, and FOXO3a
      expression through reactive oxygen species (ROS)/PI3K/AKT/AP-1.

PMID- 22978665
TI  - Photosynthetic electron transport in an anoxygenic photosynthetic bacterium
      Afifella (Rhodopseudomonas) marina measured using PAM fluorometry.
AB  - Blue diode-based pulse amplitude modulation (PAM) technology can be used to
      measure the photosynthetic electron transport rate (ETR) in a purple nonsulfur
      anoxygenic photobacterium, Afifella (Rhodopseudomonas) marina. Rhodopseudomonads
      have a reaction center light harvesting antenna complex containing an RC-2 type
      bacteriochlorophyll a protein (BChl a RC-2-LH1) which has a blue absorption peak
      and variable fluorescence similar to PSII. Absorptance of cells filtered onto
      glass fiber disks was measured using a blue-diode-based absorptance meter (Blue
      RAT) so that absolute ETR could be calculated from PAM experiments. Maximum
      quantum yield (Y) was ~0.6, decreasing exponentially as irradiance increased. ETR
      vs irradiance (P vs E) curves fitted the waiting-in-line model (ETR = (ETRmax  *
      E/Eopt ) * exp(1 - E/Eopt )). Maximum ETR (ETRmax ) was ~1000-2000 MUmol e(-) 
      mg(-1)  BChl a h(-1) . Fe(2+) , bisulfite and thiosulfate act as photosynthetic
      electron donors. Optimum irradiance was ~100 MUmol m(-2)  s(-1) PPFD even in
      Afifella grown in sunlight. Quantum efficiencies (alpha) were ~0.3-0.4 mol e(-) 
      mol hlambda(-1) ; or ~11.8 +/- 2.9 mol e(-)  mol hlambda(-1)  m(2)  MUg(-1)  BChl
      a). An underlying layer of Afifella in a constructed algal/photosynthetic
      bacterial mat has little effect on the measured ETR of the overlying
      oxyphotoautotroph (Chlorella).

PMID- 22978667
TI  - Multiple sensor array of Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ complexes of a
      triazole linked imino-phenol based calix[4]arene conjugate for the selective
      recognition of Asp, Glu, Cys, and His.
AB  - The triazole linked o-imino phenol appended calix[4]arene conjugate (L) has been
      synthesized and characterized. The structure of L has been established based on
      single crystal XRD. The binding and recognition behavior of conjugate, L toward
      the transition metal ions, such as Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and
      Zn(2+), has been demonstrated using fluorescence, absorption and ESI-MS
      techniques. The in situ prepared complexes of these metal ions, namely, [Mn(2)L],
      [Fe(2)L], [Co(2)L], [Ni(2)L], [Cu(2)L], and [Zn(2)L] have shown recognition
      toward Glu, Asp, His and Cys. Hence L provides a multiple sensing molecular tool
      where the response for the recognition of biologically active amino acids of
      metalloproteins is elicited by the presence of specific metal ion.

PMID- 22978666
TI  - Application of circular consensus sequencing and network analysis to characterize
      the bovine IgG repertoire.
AB  - BACKGROUND: Vertebrate immune systems generate diverse repertoires of antibodies
      capable of mediating response to a variety of antigens. Next generation
      sequencing methods provide unique approaches to a number of immuno-based research
      areas including antibody discovery and engineering, disease surveillance, and
      host immune response to vaccines. In particular, single-molecule circular
      consensus sequencing permits the sequencing of antibody repertoires at previously
      unattainable depths of coverage and accuracy. We approached the bovine
      immunoglobulin G (IgG) repertoire with the objective of characterizing diversity
      of expressed IgG transcripts. Here we present single-molecule real-time
      sequencing data of expressed IgG heavy-chain repertoires of four individual
      cattle. We describe the diversity observed within antigen binding regions and
      visualize this diversity using a network-based approach. RESULTS: We generated
      49,945 high quality cDNA sequences, each spanning the entire IgG variable region
      from four Bos taurus calves. From these sequences we identified 49,521 antigen
      binding regions using the automated Paratome web server. Approximately 9% of all
      unique complementarity determining 2 (CDR2) sequences were of variable lengths. A
      bimodal distribution of unique CDR3 sequence lengths was observed, with common
      lengths of 5-6 and 21-25 amino acids. The average number of cysteine residues in
      CDR3s increased with CDR3 length and we observed that cysteine residues were
      centrally located in CDR3s. We identified 19 extremely long CDR3 sequences (up to
      62 amino acids in length) within IgG transcripts. Network analyses revealed
      distinct patterns among the expressed IgG antigen binding repertoires of the
      examined individuals. CONCLUSIONS: We utilized circular consensus sequencing
      technology to provide baseline data of the expressed bovine IgG repertoire that
      can be used for future studies important to livestock research. Somatic mutation
      resulting in base insertions and deletions in CDR2 further diversifies the bovine
      antibody repertoire. In contrast to previous studies, our data indicate that
      unusually long CDR3 sequences are not unique to IgM antibodies in cattle.
      Centrally located cysteine residues in bovine CDR3s provide further evidence that
      disulfide bond formation is likely of structural importance. We hypothesize that
      network or cluster-based analyses of expressed antibody repertoires from
      controlled challenge experiments will help identify novel natural antigen binding
      solutions to specific pathogens of interest.

PMID- 22978669
TI  - Monosodium glutamate stimulates secretion of glucagon-like peptide-1 and reduces
      postprandial glucose after a lipid-containing meal.
AB  - BACKGROUND: Monosodium l-glutamate (MSG) is known to influence the endocrine
      system and gastrointestinal (GI) motility. The mechanism of postprandial glycemic
      control by food in the GI tract is mostly unknown and of great interest. AIM: To
      investigate the effect of MSG on glucose homeostasis, incretin secretion and
      gastric emptying in humans after a lipid-containing meal. METHODS: Thirteen
      healthy male volunteers (mean age, 25.5 years) and with no Helicobcter pylori
      infection were enrolled. A 400 mL (520 kcal) liquid meal with MSG (2 g, 0.5%
      wt:vol) or NaCl (control) was ingested in a single-blind placebo-controlled cross
      over study. Blood glucose, serum insulin, plasma glucagon, plasma glucagon-like
      peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were measured.
      Gastric emptying was monitored by a 13C acetate breath test. Postprandial
      symptoms were assessed on a visual analogue scale. RESULTS: The 30-min
      postprandial glucose concentration was significantly reduced by adding MSG to the
      test meal. The area under the glucose concentration vs. time curve (0-60 min) was
      also significantly reduced by adding MSG (40.6 +/- 3.51 mg.1 hr/dL with MSG vs.
      49.2 +/- 3.86 mg.1 hr/dL with NaCl, P = 0.047), whereas, the 30-min postprandial
      plasma GLP-1 level was significantly increased (58.1 +/- 15.8 pmol/L with MSG vs.
      13.4 +/- 15.8 pmol/L with NaCl, P = 0.035). MSG did not affect the half gastric
      emptying time or postprandial symptoms. CONCLUSIONS: Monosodium l-glutamate
      improved early postprandial glycaemia after a lipid-containing liquid meal. This
      effect was not associated with a change in gastric emptying, but was possibly
      related to stimulation of glucagon-like peptide-1 secretion.

PMID- 22978668
TI  - The effect of fetal androgen metabolism-related gene variants on external
      genitalia virilization in congenital adrenal hyperplasia.
AB  - The 21-hydroxylase deficiency (21OHD) is caused by CYP21A2 mutations resulting in
      severe or moderate enzymatic impairments. 21OHD females carrying similar
      genotypes present different degrees of external genitalia virilization,
      suggesting the influence of other genetic factors. Single nucleotide variants
      (SNVs) in the CYP3A7 gene and in its transcription factors, related to fetal 19
      carbon steroid metabolism, could modulate the genital phenotype. To evaluate the
      influence of the 21OHD genotypes and the CYP3A7, PXR and CAR SNVs on the genital
      phenotype in 21OHD females. Prader scores were evaluated in 183 patients. The
      CYP3A7, PXR and CAR SNVs were screened and the 21OHD genotypes were classified
      according to their severity: severe and moderate groups. Patients with severe
      genotype showed higher degree of genital virilization (Prader median III, IQR III
      IV) than those with moderate genotype (III, IQR II-III) (p < 0.001). However, a
      great overlap was observed between genotype groups. Among all the SNVs tested,
      only the CAR rs2307424 variant correlated with Prader scores (r(2)  = 0.253; p =
      0.023). The CYP21A2 genotypes influence the severity of genital virilization in
      21OHD females. We also suggest that the CAR variant, which results in a poor
      metabolizer phenotype, could account for a higher degree of external genitalia
      virilization. 

PMID- 22978671
TI  - Fifth stereoactive orbital on silicon: relaxation of the lowest singlet excited
      state of octamethyltrisilane.
AB  - We address relaxation pathways in the excited singlet states S(1) of saturated
      molecules, specifically alkylated oligosilanes. Unlike their longer peralkylated
      homologues, disilanes and trisilanes do not fluoresce even at low temperatures.
      An examination of the S(1) potential energy surface of Si(3)Me(8) with density
      functional (TDDFT, LC-TDDFT), and ab initio (RICC2, RIADC(2)) methods with TZVP
      basis sets revealed only extremely shallow minima in the vicinity of funnels,
      accounting for the absence of fluorescence, rapid internal conversion, and
      photoproducts. Relaxed singlet excited state structures either contain one
      approximately trigonal bipyramidal Si atom or two that are halfway between
      tetrahedral and trigonal bipyramidal. Four of the ligands are those that the Si
      atom had in the ground state. Natural bond orbital analysis suggests that the
      fifth one is a nonbonding hybrid orbital of the lone-pair type and size
      intermediate between valence and Rydberg, with an only very small occupancy, yet
      stereochemically active. The fifth natural hybrid orbital is composed primarily
      of 4s, 4p, and usually to a lesser degree, also 3d atomic orbitals. The trigonal
      bipyramidal structure allows an optimal accommodation of the presence of both a
      negative and a positive charge in the Lewis structures. The excess negative
      charge on the distorted Si atom is shared between the nonbonding fifth hybrid
      orbital and sigma* antibonding orbitals associated with its bonds. The positive
      charge resides in an adjacent sigma SiSi bond orbital. A Rydberg minimum also
      occurs on the S(1) surface at the geometry of the radical cation.

PMID- 22978670
TI  - A novel methylated sesquiterpene from seagrass Posidonia oceanica (L.) Delile.
AB  - Phytochemical investigation of chloroform extract from the leaves of the marine
      plant Posidonia oceanica (L.) Delile (Posidoniaceae), yielded posidozinol, a new
      methylated sesquiterpene along with beta-sitosterol and four known fatty acids:
      palmitic, palmitoleic, oleic and linoleic acids. The structure elucidation has
      been established on the basis of 1D- and 2D-NMR spectroscopy, GS/MS and ES mass
      spectrometry. Antibacterial effects of crude extracts from P. oceanica were
      evaluated against: Pseudomonas aeruginosa, Escherichia coli, Staphylococcus
      aureus, Staphylococcus epidermidis and Micrococcus luteus microorganisms. 

PMID- 22978672
TI  - Gd4Ge(3-x)Pn(x) (Pn = P, Sb, Bi, x = 0.5-3): stabilizing the nonexisting Gd4Ge3
      binary through valence electron concentration. Electronic and magnetic properties
      of Gd4Ge(3-x)Pn(x).
AB  - Gd(4)Ge(3-x)Pn(x) (Pn = P, Sb, Bi; x = 0.5-3) phases have been prepared and
      characterized using X-ray diffraction, wavelength-dispersive spectroscopy, and
      magnetization measurements. All Gd(4)Ge(3-x)Pn(x) phases adopt a cubic anti
      Th(3)P(4) structure, and no deficiency on the Gd or p-element site could be
      detected. Only one P-containing phase with the Gd(4)Ge(2.51(5))P(0.49(5))
      composition could be obtained, as larger substitution levels did not yield the
      phase. Existence of Gd(4)Ge(2.51(5))P(0.49(5)) and Gd(4)Ge(2.49(3))Bi(0.51(3))
      suggests that the hypothetical Gd(4)Ge(3) binary can be easily stabilized by a
      small increase in the valence electron count and that the size of the p element
      is not a key factor. Electronic structure calculations reveal that large
      substitution levels with more electron-rich Sb and Bi are possible for charge
      balanced (Gd(3+))(4)(Ge(4-))(3) as extra electrons occupy the bonding Gd-Gd and
      Gd-Ge states. This analysis also supports the stability of Gd(4)Sb(3) and
      Gd(4)Bi(3). All Gd(4)Ge(3-x)Pn(x) phases order ferromagnetically with relatively
      high Curie temperatures of 234-356 K. The variation in the Curie temperatures of
      the Gd(4)Ge(3-x)Sb(x) and Gd(4)Ge(3-x)Bi(x) series can be explained through the
      changes in the numbers of conduction electrons associated with  Ge/Sb(Bi)
      substitution.

PMID- 22978673
TI  - Parvovirus B19V DNA contamination in Chinese plasma and plasma derivatives.
AB  - BACKGROUND: To ensure the safety of plasma derivatives, screening for human
      parvovirus B19V genomic DNA in donated plasma using a pooling strategy is
      performed in some countries. We investigated the prevalence of B19V DNA and anti
      B19V antibodies in Chinese plasma pools, plasma derivatives and plasma donations
      to evaluate the risk posed by B19V. METHODS: Using a Q-PCR assay developed in
      house, we tested for B19V genomic DNA in 142 plasma pools collected between
      January 2009 and June 2011 from two Chinese blood products manufacturers. Plasma
      derivatives collected between 1993-1995 (10 batches of albumin, 155 batches of
      intravenous immunoglobulin, IVIG) and 2009-2011 (50 batches of albumin, 54
      batches of IVIG, 35 batches of factor VIII, 7 batches of fibrinogen, and 17
      batches of prothrombin complex concentrate, PCC) were also tested for B19V
      contamination. In addition, B19V genome prevalence in minipools(including 90
      individual donations) of 49680 individual plasma samples collected between August
      2011 and March 2012 by a single Chinese manufacturer was investigated. IgM/IgG
      was also investigated in plasma pools/derivatives and in minipools with B19V-DNA
      titers above 1x10(4) and 1x10(6) geq/mL using B19 ELISA IgM/IgG assay(Virion
      Serion, Wurzburg, Germany), respectively. RESULTS: B19V-DNA was detected in 54.2%
      of plasma pools from two Chinese blood product manufacturers; among recently
      produced blood products, B19V was detected in 21/54 IVIG samples, 19/35 factor
      VIII samples, 6/7 fibrinogen samples, and 12/17 PCC samples, but not in albumin
      samples. The levels of B19V-DNA in these samples varied from 10(2)-10(7) geq/mL.
      In samples with >10(4) geq/mL genome DNA, B19V-specific IgG was also found in all
      corresponding plasma pools and IVIG, whereas none was detected in the majority of
      other plasma derivatives. Screening of plasma donations indicated that most
      minipools were contaminated with B19V-DNA (10(2)-10(8) geq/mL) and one donation
      had 1.09 * 10(10) geq/mL B19V genomic DNA along with a non-classical IgG/IgM
      profile. CONCLUSIONS: Despite the implementation of some inactivation/removal
      methods designed to prevent viral contamination, B19V DNA was detectable in
      Chinese plasma pools and plasma derivatives. Thus, the introduction of B19V
      screening and discard donation with high viramic concentration for Chinese plasma
      donors would be desirable.

PMID- 22978674
TI  - Synthesis and biological evaluation of epidithio-, epitetrathio-, and bis
      (methylthio)diketopiperazines: synthetic methodology, enantioselective total
      synthesis of epicoccin G, 8,8'-epi-ent-rostratin B, gliotoxin, gliotoxin G,
      emethallicin E, and haematocin and discovery of new antiviral and antimalarial
      agents.
AB  - An improved sulfenylation method for the preparation of epidithio-, epitetrathio
      , and bis-(methylthio)diketopiperazines from diketopiperazines has been
      developed. Employing NaHMDS and related bases and elemental sulfur or
      bis[bis(trimethylsilyl)amino]trisulfide (23) in THF, the developed method was
      applied to the synthesis of a series of natural and designed molecules, including
      epicoccin G (1), 8,8'-epi-ent-rostratin B (2), gliotoxin (3), gliotoxin G (4),
      emethallicin E (5), and haematocin (6). Biological screening of selected
      synthesized compounds led to the discovery of a number of nanomolar
      antipoliovirus agents (i.e., 46, 2,2'-epi-46, and 61) and several low-micromolar
      anti- Plasmodium falciparum  lead compounds (i.e., 46, 2,2'-epi-46, 58, 61, and
      1).

PMID- 22978675
TI  - Arabidopsis wat1 (walls are thin1)-mediated resistance to the bacterial vascular
      pathogen, Ralstonia solanacearum, is accompanied by cross-regulation of salicylic
      acid and tryptophan metabolism.
AB  - Inactivation of Arabidopsis WAT1 (Walls Are Thin1), a gene required for secondary
      cell-wall deposition, conferred broad-spectrum resistance to vascular pathogens,
      including the bacteria Ralstonia solanacearum and Xanthomonas campestris pv.
      campestris, and the fungi Verticillium dahliae and Verticillium albo-atrum.
      Introduction of NahG, the bacterial salicylic acid (SA)-degrading salicylate
      hydroxylase gene, into the wat1 mutant restored full susceptibility to both R.
      solanacearum and X. campestris pv. campestris. Moreover, SA content was
      constitutively higher in wat1 roots, further supporting a role for SA in wat1
      mediated resistance to vascular pathogens. By combining transcriptomic and
      metabolomic data, we demonstrated a general repression of indole metabolism in
      wat1-1 roots as shown by constitutive down-regulation of several genes encoding
      proteins of the indole glucosinolate biosynthetic pathway and reduced amounts of
      tryptophan (Trp), indole-3-acetic acid and neoglucobrassicin, the major form of
      indole glucosinolate in roots. Furthermore, the susceptibility of the wat1 mutant
      to R. solanacearum was partially restored when crossed with either the trp5
      mutant, an over-accumulator of Trp, or Pro35S:AFB1-myc, in which indole-3-acetic
      acid signaling is constitutively activated. Our original hypothesis placed cell
      wall modifications at the heart of the wat1 resistance phenotype. However, the
      results presented here suggest a mechanism involving root-localized metabolic
      channeling away from indole metabolites to SA as a central feature of wat1
      resistance to R. solanacearum.

PMID- 22978676
TI  - Molecular characterization of the bla(KPC-2) gene in clinical isolates of
      carbapenem-resistant  Klebsiella pneumoniae  from the pediatric wards of a
      Chinese hospital.
AB  - The present study was conducted to confirm the presence of  Klebsiella pneumoniae
      carbapenemase (KPC)-producing K. pneumoniae associated with a nosocomial
      outbreak in a Chinese pediatric hospital. From July 2009 to January 2011, 124
      nonduplicated K. pneumoniae isolates were collected from specimens from patients
      of pediatric units in the hospital. Twelve of the 124 isolates possessed the
      bla(KPC-2) gene and showed 7 different pulsed-field gel electrophoresis (PFGE)
      patterns. Meanwhile, 16S rRNA methylase, acc(6')-Ib-cr, and several types of beta
      lactamases were also produced by the majority of the KPC-producing isolates.
      Class 1 integron-encoded intI1 integrase gene was subsequently found in all
      strains, and amplification, sequencing, and comparison of DNA between 5'
      conserved segment and 3' conserved segment region showed the presence of several
      known antibiotic resistance gene cassettes of various sizes. The conjugation and
      plasmid-curing experiments indicated some KPC-2-encoding genes were
      transmissible. In addition, conjugal cotransfer of multidrug-resistant phenotypes
      with KPC-positive phenotypes was observed in KPC-producing strains. Restriction
      endonuclease analysis and DNA hybridization with a KPC-specific probe showed that
      the bla(KPC-2) gene was carried by plasmid DNA from K. pneumoniae of PFGE pattern
      B. The overall results indicate that the emergence and outbreak of KPC-producing
      K. pneumoniae in our pediatric wards occurred in conjunction with plasmids
      coharboring 16S rRNA methylase and extended-spectrum beta-lactamases.

PMID- 22978677
TI  - NMR structure, localization, and vesicle fusion of Chikungunya virus fusion
      peptide.
AB  - The virus-host cell fusion process is mediated by a membrane anchored viral
      fusion protein that inserts its hydrophobic fusion peptide into the plasma
      membrane of the host cell, initiating the fusion reaction. Therefore, fusion
      peptides are an important functional constituent of the fusion proteins of
      enveloped viruses. In this work, we characterize the fusion peptide or VT18
      (V(84)YPFMWGGAYCFCDAENT(101)) of Chikungunya virus (CHIKV) using NMR and
      fluorescence spectroscopy in zwitterionic lipid environments. Our results
      demonstrate that the VT18 peptide is able to induce liposome fusions in a pH
      independent manner and interacts with the zwitterionic lipid vesicles. The NMR
      derived three-dimensional structure of VT18, in solution of dodecylphosphocholine
      (DPC) micelles, is typified by extended or beta-type conformations for most of
      the residues, whereby residues M88-W89-G90-G91 adopt a type I beta-turn
      conformation. Strikingly, the aromatic side chains of residues Y85, F87, Y93, and
      F95 in the VT18 structure are found to be well-packed forming an aromatic core.
      In particular, residue F87 is situated at the center of the aromatic core
      establishing a close proximity with other aromatic side chains. Further, the
      aromatic core residues are also involved in packing interactions with the side
      chains of residues M88, C94. Paramagnetic relaxation enhancement NMR, using spin
      labeled doxyl lipids, indicated that the aromatic core residues of VT18 are well
      inserted into the micelles, whereas the polar residues at the C-terminus may be
      surface localized. The atomic resolution structure and lipid interactions of
      CHIKV fusion peptide presented here will aid to uncover the fusion mechanism by
      the type II viral fusion proteins.

PMID- 22978679
TI  - Li+ solvation and transport properties in ionic liquid/lithium salt mixtures: a
      molecular dynamics simulation study.
AB  - Molecular dynamics simulations of N-methyl-N-propylpyrrolidinium (pyr(13))
      bis(trifluoromethanesulfonyl)imide (Ntf(2)) ionic liquid [pyr(13)][Ntf(2)] mixed
      with [Li][Ntf(2)] salt have been conducted using a polarizable force field.
      Mixture simulations with lithium salt mole fractions between 0% and 33% at 363
      and 423 K yield densities, ion self-diffusion coefficients, and ionic
      conductivities in very good agreement with available experimental data. In all
      investigated electrolytes, each Li(+) cation was found to be coordinated, on
      average, by 4.1 oxygen atoms from surrounding anions. At lower concentrations (x
      <= 0.20), the Li(+) cation was found to be, on average, coordinated by slightly
      more than three Ntf(2) anions with two anions contributing a single oxygen atom
      and one anion contributing two oxygen atoms to Li(+) coordination. At the highest
      [Li][Ntf(2)] concentration, however, there were, on average, 3.5 anions
      coordinating each Li(+) cation, corresponding to fewer bidendate and more
      monodentate anions in the Li(+) coordination sphere. This trend is due to
      increased sharing of anions by Li(+) at higher salt concentrations. In the
      [pyr(13)][Ntf(2)]/[Li][Ntf(2)] electrolytes, the ion diffusivity is significantly
      smaller than that in organic liquid electrolytes due to not only the greater
      viscosity of the solvent but also the formation of clusters resulting from
      sharing of anions by Li(+) cations. The ionic conductivity of the electrolytes
      was found to decrease with increasing salt concentration, with the effect being
      greater at the higher temperature. Finally, we found that the contribution of
      Li(+) to ionic conductivity does not increase proportionally to Li(+)
      concentration but saturates at higher doping levels.

PMID- 22978680
TI  - Origin of the contact angle hysteresis of water on chemisorbed and physisorbed
      self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) are known to form on a variety of substrates
      either via chemisorption (i.e., through chemical interactions such as a covalent
      bond) or physisorption (i.e., through physical interactions such as van der Waals
      forces or "ionic" bonds). We have studied the behavior and effects of water on
      the structures and surface energies of both chemisorbed octadecanethiol and
      physisorbed octadecylamine SAMs on GaAs using a number of complementary
      techniques including "dynamic" contact angle measurements (with important time
      and rate-dependent effects), AFM, and electron microscopy. We conclude that both
      molecular overturning and submolecular structural changes occur over different
      time scales when such SAMs are exposed to water. These results provide new
      insights into the time-dependent interactions between surfaces and colloids
      functionalized with SAMs when synthesized in or exposed to high humidity or bulk
      water or wetted by water. The study has implications for a wide array of
      phenomena and applications such as adhesion, friction/lubrication and wear
      (tribology), surfactant-solid surface interactions, the organization of
      surfactant-coated nanoparticles, etc.

PMID- 22978678
TI  - Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine
      self-administration during adulthood in male C57BL/6J mice.
AB  - Studies of adolescent drug use show (1) a pattern in which the use of tobacco
      precedes the use of other drugs and (2) a positive relationship between
      adolescent tobacco use and later drug use. These observations have led to the
      hypothesis that a causal relationship exists between early exposure to nicotine
      and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we
      tested the hypothesis that nicotine exposure in adolescence leads to increased
      intravenous self-administration (IVSA) of cocaine in adulthood. Using miniature
      osmotic pumps, we exposed mice and their littermate controls to nicotine (24
      mg/kg/day) or vehicle, respectively, over the entire course of adolescence
      [postnatal days (P) 28-56]. Nicotine exposure was terminated on P56 and mice were
      not exposed to nicotine again during the experiment. On P73, mice were allowed to
      acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose-response curve was generated
      (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction
      conditions was also evaluated. All mice rapidly learned to lever press for the
      combination of cocaine infusions and non-drug stimuli. Analysis of the dose
      response curve revealed that adolescent nicotine-exposed mice self-administered
      significantly more (P < 0.05) cocaine than controls at all but the highest dose.
      No significant differences were observed between adolescent nicotine-exposed and
      control mice during the acquisition or extinction stages. These results indicate
      that adolescent nicotine exposure can increase cocaine IVSA in mice, which
      suggests the possibility of a causal link between adolescent tobacco use and
      later cocaine use in humans. 

PMID- 22978681
TI  - SPInDel: a multifunctional workbench for species identification using
      insertion/deletion variants.
AB  - The majority of the available methods for the molecular identification of species
      use pairwise sequence divergences between the query and reference sequences (DNA
      barcoding). The presence of multiple insertions and deletions (indels) in the
      target genomic regions is generally regarded as a problem, as it introduces
      ambiguities in sequence alignments. However, we have recently shown that a high
      level of species discrimination is attainable in all taxa of life simply by
      considering the length of hypervariable regions defined by indel variants. Each
      species is tagged with a numeric profile of fragment lengths-a true numeric
      barcode. In this study, we describe a multifunctional computational workbench
      (named SPInDel for SPecies Identification by Insertions/Deletions) to assist
      researchers using variable-length DNA sequences, and we demonstrate its
      applicability in molecular ecology. The SPInDel workbench provides a step-by-step
      environment for the alignment of target sequences, selection of informative
      hypervariable regions, design of PCR primers and the statistical validation of
      the species-identification process. In our test data sets, we were able to
      discriminate all species from two genera of frogs (Ansonia and Leptobrachium)
      inhabiting lowland rainforests and mountain regions of South-East Asia and
      species from the most common genus of coral reef fishes (Apogon). Our method can
      complement conventional DNA barcoding systems when indels are common (e.g. in
      rRNA genes) without the required step of DNA sequencing. The executable files,
      source code, documentation and test data sets are freely available at
      http://www.portugene.com/SPInDel/SPInDel_webworkbench.html.

PMID- 22978682
TI  - Quality of life predicts survival in patients with non-small cell lung cancer.
AB  - BACKGROUND: Patients with non-small cell lung cancer (NSCLC) have a poor
      prognosis. The objective of this study was to examine the relationship of EORTC
      QLQ-C30 and QLQ-LC13 and survival in patients with NSCLC undergoing different
      treatments. METHODS: Investigators conducted a health-related quality of life
      (HRQOL) survey of 488 patients with NSCLC: 162 patients undergoing surgery, 312
      patients without surgery, and their survival status was prospectively followed
      up. EORTC QLQ-C30 and QLQ-LC13 scores and clinical variables at baseline were
      analyzed using Cox's proportional hazard regression to identify factors that
      influenced survival. RESULTS: Median survival of these 474 patients was 9.82
      months. After adjustment, emotional functioning scale, and symptom scales of pain
      and nausea/vomiting are associated with survival in NSCLC patients with surgery
      whereas social functioning scale, and symptom scales for fatigue, appetite loss,
      and financial problems had a significant impact on survival in NSCLC patients
      without surgery. The results of multivariate analysis showed that none of QLQ
      LC13 scales are significant predictors of survival. After simultaneously
      considering these scales, we found significant independent predictors of survival
      were nausea/vomiting (HR = 0.11, 95% CI = 0.02-0.63 for score >0 compared with
      =0) in NSCLC patients with surgery and appetite loss (HR = 1.77, 95% CI = 1.26
      2.49 for score >0 compared with =0) in NSCLC patients without surgery.
      CONCLUSIONS: HRQOL provides additional predictive information that supplements
      traditional clinical factors, and is a new prognostic indicator for survival of
      NSCLC patients under different treatments.

PMID- 22978683
TI  - Molecular basis of drug resistance in A/H1N1 virus.
AB  - New mutants of human influenza virus (A/H1N1) exhibit resistance to antiviral
      drugs. The mechanism whereby they develop insensitivity to these medications is,
      however, not yet completely understood. A crystallographic structure of A/H1N1
      neuraminidase has been published recently. Using molecular dynamic simulations,
      it is now possible to characterize at the atomic level the mechanism that
      underlies the loss of binding affinity of the drugs. In this study, free-energy
      perturbation was used to evaluate the relative binding free energies of Tamiflu
      and Relenza with H274Y, N294S, and Y252H neuraminidase mutants. Our results
      demonstrate a remarkable correlation between theoretical and experimental data,
      which quantitatively confirms that the mutants are resistant to Tamiflu but are
      still strongly inhibited by Relenza. The simulations further reveal the key
      interactions that govern the affinity of the two drugs for each mutant. This
      information is envisioned to prove useful for the design of novel neuraminidase
      inhibitors and for the characterization of new potential mutants.

PMID- 22978684
TI  - Rituximab and chlorambucil versus rituximab alone in gastric mucosa-associated
      lymphoid tissue lymphoma according to t(11;18) status: a monocentric non
      randomized observational study.
AB  - Forty-nine patients, t(11;18)-positive (n = 31) and t(11;18)-negative (n = 18),
      were treated without randomization with rituximab-chlorambucil or rituximab
      alone. Evaluation was performed at week (W) 6, week (W) 25 and every 6 months
      (Wx). Comparing the rituximab-chlorambucil group to the rituximab-alone group,
      remission was obtained in 93% vs. 66% at W6 (p = 0.01), in 93% vs. 81% at W25 (p
      = 0.14) and in 93% vs. 76% at Wx (p = 0.07). Comparing the rituximab-chlorambucil
      group to the rituximab-alone group in t(11;18)-positive patients, remission was
      obtained in 100% vs. 45% at W6 (p = 0.0005), in 100% vs. 66% at W25 (p = 0.01)
      and in 96% vs. 55% at Wx (p = 0.01). Comparing the rituximab-chlorambucil group
      to the rituximab-alone group in t(11;18)-negative patients, remission was
      obtained in 66% vs. 83% at W6 (p = 0.32), in 66% vs. 92% at W25 (p = 0.22) and in
      83% vs. 92% at Wx (p = 0.47). In conclusion, rituximab-chlorambucil is
      significantly more rapidly efficient than rituximab alone. In t(11;18)-positive
      patients, the combination is more efficient than rituximab alone. In t(11;18)
      negative patients, rituximab alone is as efficient as rituximab-chlorambucil and
      may be an alternative treatment.

PMID- 22978685
TI  - The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin
      lymphoma: a phase I, open-label, single dose-escalation study.
AB  - Polo-like kinase 1 (Plk1) is expressed during mitosis and overexpressed in
      multiple cancers, including non-Hodgkin lymphoma (NHL). This phase I study
      determined the maximum tolerated dose (MTD) of BI 2536, a Plk1 inhibitor, as a 1
      h infusion once every 3 weeks in post-transplant relapsed (n = 17) and transplant
      naive (n = 24) patients with relapsed/refractory NHL. Median treatment cycles
      were 2 and 1.5, respectively. MTD was 175 mg for both populations; dose-limiting
      toxicities were grade 4 thrombocytopenia and neutropenia. Most treatment-related
      adverse events were grade 1/2; drug-related grade 3/4 events included
      thrombocytopenia and neutropenia. Four patients achieved responses (three
      complete and one partial at doses >= 150 mg, all post-transplant relapsed
      patients) for an overall response rate of 9.8%. BI 2536 exhibited multi
      compartmental pharmacokinetics with a high volume of distribution. The activity
      and safety of BI 2536 in this pretreated patient population support Plk
      inhibitors as a therapeutic strategy in oncology.

PMID- 22978686
TI  - Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced
      febrile neutropenia in patients with hematological malignancies.
AB  - Recent studies have shown the prophylactic efficacy of fluoroquinolones against
      infections in patients with chemotherapy-induced neutropenia. However, little is
      known about the differences between fluoroquinolones, and there are some concerns
      about the emergence of resistant bacteria. In this retrospective study, we
      compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX)
      for chemotherapy-induced febrile neutropenia. The cumulative incidences of
      febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of
      270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a
      more prominent prophylactic advantage of MFLX in patients with acute myeloid
      leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008,
      respectively). There were no significant differences in the incidences of adverse
      events and fluoroquinolone resistant bacteria in both groups. This study
      indicates that prophylaxis with MFLX is more beneficial to reduce febrile
      neutropenia episodes than TFLX, especially in patients with high-risk disease.

PMID- 22978687
TI  - In thyroidectomized patients with thyroid cancer, a serum thyrotropin of 30
      MUU/mL after thyroxine withdrawal is not always adequate for detecting an
      elevated stimulated serum thyroglobulin.
AB  - BACKGROUND: The thyrotropin (TSH) level or duration of thyroid hormone withdrawal
      (THW) required to detect stimulated thyroglobulin (Tg) in differentiated thyroid
      cancer (DTC) monitoring is unknown. The objective of this study was to evaluate
      the TSH cutoff of >30 MUU/mL as a means to detect stimulated Tg >=2 ng/mL after
      THW (THW-Tg>=2), and sensitivity of the Functional Assessment of Chronic Illness
      Therapy-Fatigue (FACIT-F) questionnaire for detecting hypothyroid symptoms.
      METHODS: This was a prospective longitudinal cohort study done at a tertiary
      academic medical center. Forty-seven patients with DTC undergoing their first Tg
      stimulation or after previously abnormal Tg stimulation had weekly measurements
      of TSH and Tg during the 4 weeks THW, and repeated questionnaire assessments.
      RESULTS: TSH did not reach a plateau in any patient, and in those whose Tg did
      not remain undetectable, Tg continued to rise. Seventy-five percent of patients
      had an undetectable Tg <0.2 ng/mL at baseline (95% were <0.5 mg/mL) with 16%
      remaining undetectable throughout THW. The majority of patients (72.7% and 97.8%)
      achieved TSH >30 MUU/mL by 3 and 4 weeks THW, respectively. Of the 15 patients
      with maximum stimulated THW-Tg>=2, 38% were detected before the minimal TSH >30
      MUU/mL cutoff. At 2 weeks THW, 3 had a TSH>30 MUU/mL, and none of them had Tg >=2
      ng/mL. At 3 weeks THW, 11 had a TSH >30 MUU/mL, and 64% of them had Tg >=2 ng/mL.
      Only 60% were detected at 3-week THW regardless of their TSH level. Eighty-six
      percent were detected by TSH 60-<80 MUU/mL. Conversely, all patients whose serum
      Tg was <0.2 ng/mL when their serum TSH was >20 MUU/mL did not achieve a THW
      Tg>=2. CONCLUSION: The minimal TSH cutoff of >30 MUU/mL was inadequate to detect
      many patients with final stimulated THW-Tg>=2 during complete THW. TSH >80-100
      MUU/mL was a better cutoff, achieved in only 53% after 4-week THW. Conversely, we
      propose a preliminary THW-stopping rule for ending THW early in selected
      patients. In patients with a Tg <0.2 ng/mL when TSH >20 MUU/mL, all had a final
      stimulated Tg <=2 ng/mL, potentially saving qualifying patients 40% of THW
      duration compared to 4-week THW. FACIT-F correlated with TSH, but was not
      sensitive to detect mild hypothyroidism.

PMID- 22978688
TI  - Low recurrence rate in treating atrioventricular nodal reentrant tachycardia with
      triple freeze-thaw cycles.
AB  - BACKGROUND: Cryoablation is an alternative to radiofrequency ablation in treating
      atrioventricular nodal reentrant tachycardia (AVNRT). However, its long-term
      effectiveness is in question when compared to radiofrequency ablation. We
      reviewed the results of cryoablation in children with AVNRT at our institute.
      METHODS: We performed a retrospective single-center chart review of consecutive
      patients <=18 years of age with AVNRT who underwent cryoablation between January
      2007 and August 2009. During cryoablation, a 6-mm-tip cryocatheter was used with
      temperature set to -80 degrees C. Test lesions were performed at the presumed
      slow pathway location based on combined anatomic and electrophysiologic approach.
      If successful, ablation was then continued with triple freeze-thaw cycles (FTC)
      of 4 minutes each. RESULTS: A total of 53 patients (age range: 6.1-18.4 years,
      mean: 13.6 years, median: 13.2 years) underwent slow pathway modification with
      cryoablation. Acute success was achieved in 51 (96.2%) cases. Transient
      atrioventricular block was seen in 19 cases. The block occurred during FTC in
      eight patients (15%). The number of FTC was three in 47 (92.2%) patients. Less
      than three FTC were given in two patients due to transient heart block and four
      FTC were given in two patients with suspected catheter movement. Procedure
      duration was 177 +/- 56 minutes; fluoroscopic time was 14 +/- 11 minutes. Mean
      follow-up was 30.7 +/- 10 (range 12-52, median 31) months. Recurrence of
      supraventricular tachycardia was seen in only one (1.96%) patient. CONCLUSIONS:
      Triple FTC cryoablation lesions resulted in a low recurrence rate comparable to
      RF ablation in treating AVNRT without increased complications.

PMID- 22978691
TI  - Virus factories: biogenesis and structural design.
AB  - Replication and assembly of many viruses occur in specific intracellular
      compartments known as 'virus factories'. Our knowledge of the biogenesis and
      architecture of these unique structures has increased considerably in the last 10
      years, due to technical advances in cellular, molecular and structural biology.
      We now know that viruses build replication organelles, which recruit cell and
      viral components in a macrostructure in which viruses assemble and mature. Cell
      membranes and cytoskeleton participate in the biogenesis of these scaffolds and
      mitochondria are present in many factories, where they might supply energy and
      other essential factors. New inter-organelle contacts have been visualized within
      virus factories, whose structure is very dynamic, as it changes over time. There
      is increasing interest in identifying the factors involved in their biogenesis
      and functional architecture, and new microscopy techniques are helping us to
      understand how these complex entities are built and work. In this review, we
      summarize recent findings on the cell biology, biogenesis and structure of virus
      factories.

PMID- 22978690
TI  - The anti-obesity potential of sigmoidin A.
AB  - CONTEXT: During the last few decades, the prevalence of obesity in the western
      world has dramatically increased with epidemic proportions. Hand in hand with
      this statistic, the incidences of obesity-linked diseases such as diabetes are
      increasing with pandemic rate. The search for novel drugs and nutritional
      intervention approaches for obesity is now of significant importance. OBJECTIVE:
      The anti-obesity potential of eriodictyol (ERD) and its close structural
      analogue, sigmoidin A (SGN), were evaluated. SGN was isolated from Erythrina
      abyssinica Lam. ex DC. (Fabaceae). MATERIALS AND METHODS: Concentrations between
      300 and 0.1 uM of test samples and reference drugs made in three-fold dilutions
      were tested for enzyme inhibitory effects. The major obesity target, pancreatic
      lipase, was used to test the anti-obesity potential while the selective effects
      of the compounds were determined through assessments of effects on alpha
      glucosidase. RESULTS: The inhibitory effect of SGN on pancreatic lipase (IC50,
      4.5 +/- 0.87 uM) was 30-times greater than that of ERD (IC50, 134 +/- 19.39 uM)
      while their effect on alpha-glucosidase enzyme was comparable (IC50 value of 62.5
      +/- 9.47 and 57.5 +/- 13.15 uM). The anti-obesity drug, orlistat, inhibited
      pancreatic lipase with an IC50 value of 0.3 +/- 0.04 uM, while the anti-diabetic
      drug, acarbose, inhibited alpha-glucosidase with an IC50 value of 190.6 +/- 16.05
      uM. DISCUSSION: Although less active than the standard anti-obesity drug,
      orlistat, the observed activity indicated that prenylation of the flavonoid
      skeleton potently enhances anti-lipase activity. CONCLUSION: Such groups of
      flavonoids need to be further investigated for their therapeutic and nutritional
      benefit in combating obesity problems.

PMID- 22978689
TI  - Cystatin C and asymptomatic coronary artery disease in patients with metabolic
      syndrome and normal glomerular filtration rate.
AB  - BACKGROUND: All of the components of metabolic syndrome (MetS) have been regarded
      as risk factors for coronary artery disease (CAD). Early detection of CAD in
      asymptomatic patients with MetS remains a challenge. Cystatin C,which has been
      proposed as a novel marker of renal dysfunction,is correlated with mortality in
      CAD, The purpose of the study was to evaluate whether cystatin C is a potential
      marker of asymptomatic CAD in MetS patients with normal kidney function. METHODS:
      A total of 211asymptomatic MetS patients without prior history of CAD patients
      were included in a cross-sectional study. Patients were divided into MetS with
      asymptomatic CAD (n=136) and MetS without CAD (n=75) groups according to coronary
      angiograph results. Serum cystatin C levels were measured using particle enhanced
      immunonephelometric assays. We first assessed whether there is an independent
      association of cystatin C with the presence and severity of asymptomatic CAD.
      Then, we investigated the association between cystatin C and other biochemical
      risk factors for atherosclerosis. RESULTS: Serum cystatin C levels in patients
      with asymptomatic CAD were significantly higher than those without CAD (P=0.004).
      A multiple logistic regression analysis demonstrated cystatin C was independently
      associated with the presence of asymptomatic CAD (OR=1.326, 95%CI: 1.086-1.619).
      On receiver operating characteristics (ROC) analysis, the area under the curve
      (AUC) was 0.622 (95% CI: 0543-0.701, P=0.003), and cystatin C showed a moderate
      predictive value. Furthermore, cystatin C was independently correlated with
      Gensini score (standardized beta=0.183, P=0.007), and serum cystatin C levels
      increased with the increasing of number of disease vessels (P=0.005). In a
      multiple stepwise regression analysis, uric acid (UA)(P<0.001), body mass index
      (BMI)(P=0.002), triglyceride(TG)(P=0.03), estimated glomerular filtration rate
      (eGFR)(P<0.001), and fibrinogen(P=0.001) were independently associated with
      cystatin C. CONCLUSIONS: Serum cystatin C in our study was significantly
      associated with the presence and severity of asymptomatic CAD in MetS patients
      with normal kidney function, suggesting that cystatin C is probably more than a
      marker of glomerular filtration rate.

PMID- 22978692
TI  - Standard of care, professional obligations, and distributive justice.
AB  - The problem of standard-of-care in clinical research concerns the level of care
      that investigators ought to provide to research subjects in the control arm of
      their clinical trials. Commentators differ sharply on whether subjects in trials
      conducted in lower income countries should be provided with the same level of
      care as subjects in trials conducted in higher income countries. I consider an
      argument that commentators have employed on both sides of this debate:
      professional role arguments. These arguments claim to justify a conclusion to the
      standard-of-care problem solely by appeal to the professional obligations that
      investigators possess. I argue that prominent versions of professional role
      arguments cannot justify a solution to the problem of standard-of-care that is
      both determinate and reasonable simply by appeal to the professional obligations
      of investigators. Instead, to do so, one must also (1) determine the level of
      care or types of treatment that individuals are entitled to as a matter of
      distributive justice, and (2) identify which agents possess the duties that
      correspond to these entitlements. The level of care that investigators owe to
      subjects in the control arm of their clinical trials is thus in part dependent on
      the level of care that these subjects are entitled to as a matter of distributive
      justice, and whether it is the investigators who possess the corresponding
      distributive obligation to provide them with the care that they are entitled to. 

PMID- 22978693
TI  - Factors influencing the implementation of fall-prevention programmes: a
      systematic review and synthesis of qualitative studies.
AB  - BACKGROUND: More than a third of people over the age of 65 years fall each year.
      Falling can lead to a reduction in quality of life, mortality, and a risk of
      prolonged hospitalisation. Reducing and preventing falls has become an
      international health priority. To help understand why research evidence has often
      not been translated into changes in clinical practice, we undertook a systematic
      review and synthesis of qualitative research in order to identify what factors
      serve as barriers and facilitators to the successful implementation of fall
      prevention programmes. METHODS: We conducted a review of literature published
      between 1980 and January 2012 for qualitative research studies that examined
      barriers and facilitators to the effective implementation of fall-prevention
      interventions among community-dwelling older people and healthcare professionals.
      Two reviewers independently screened studies for inclusion, extracted data, and
      assessed methodological quality according to predefined criteria. Findings were
      synthesised using meta-ethnography. RESULTS: Of the 5010 articles identified
      through database searching, 19 were included in the review. Analysis of the 19
      studies revealed limited information about the mechanisms by which barriers to
      implementation of fall-prevention interventions had been overcome. Data synthesis
      produced three overarching concepts: (1) practical considerations, (2) adapting
      for community, and (3) psychosocial. A line of argument synthesis describes the
      barriers and facilitators to the successful implementation of fall-prevention
      programmes. These concepts show that the implementation of fall-prevention
      programmes is complex and multifactorial. This is the first systematic review and
      synthesis of qualitative studies to examine factors influencing the
      implementation of fall-prevention programmes from the perspectives of both the
      healthcare professional and the community-dwelling older person. CONCLUSIONS: The
      current literature on barriers and facilitators to the implementation of fall
      prevention programmes examines a variety of interventions. However, the ways in
      which the interventions are reported suggests there are substantial
      methodological challenges that often inhibit implementation into practice. We
      recommend that successful implementation requires individuals, professionals, and
      organisations to modify established behaviours, thoughts, and practice. The
      issues identified through this synthesis need to be fully considered and
      addressed if fall-prevention programmes are to be successfully implemented into
      clinical practice.

PMID- 22978695
TI  - A new cytotoxic steroidal saponin from the rhizomes and roots of Smilax
      scobinicaulis.
AB  - A phytochemical investigation of the EtOH extract from the rhizomes and roots of
      Smilax scobinicaulis resulted in the isolation of a new isospirostanol-type
      steroidal saponin, namely (25 R)-5alpha-spirostan-3beta,6beta-diol 3-O-beta-D
      glucopyranosyl-(1 -> 4)-[alpha-L-arabinopyranosyl-(1 -> 6)]-beta-D
      glucopyranoside (1), along with four known steroidal saponins (2-5). The
      structures of these compounds were determined by 1D- and 2D-NMR spectroscopic
      analysis, FABMS and HR-ESI-MS as well as chemical degradation. The isolated
      saponins were evaluated for their in vitro cytotoxicity against A549, LAC and
      Hela human cancer cell lines, which demonstrated that only compound 1 possessed
      significant cytotoxic activity with IC50 values of 3.70, 5.70 and 3.64 uM,
      respectively.

PMID- 22978696
TI  - Evaluating rare coding variants as contributing causes to non-syndromic cleft lip
      and palate.
AB  - Rare coding variants are a current focus in studies of complex disease.
      Previously, at least 68 rare coding variants were reported from candidate gene
      sequencing studies in non-syndromic cleft lip and palate (NSCL/P), a common birth
      defect. Advances in sequencing technology have now resulted in thousands of
      sequenced exomes, providing a large resource for comparative genetic studies. We
      collated rare coding variants reported to contribute to NSCL/P and compared them
      to variants identified from control exome databases to determine if some might be
      rare but benign variants. Seventy-one percentage of the variants described as
      etiologic for NSCL/P were not present in the exome data, suggesting that many
      likely contribute to disease. Our results strongly support a role for rare
      variants previously reported in the majority of NSCL/P candidate genes but
      diminish support for variants in others. However, because clefting is a complex
      trait it is not possible to be definitive about the role of any particular
      variant for its risk for NSCL/P. 

PMID- 22978694
TI  - Oxidative stress and chromatin remodeling in chronic obstructive pulmonary
      disease and smoking-related diseases.
AB  - SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) is predominantly a
      tobacco smoke-triggered disease with features of chronic low-grade systemic
      inflammation and aging (inflammaging) of the lung associated with steroid
      resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative
      stress induces various kinase signaling pathways leading to chromatin
      modifications (histone acetylation/deacetylation and histone
      methylation/demethylation) in inflammation, senescence, and steroid resistance.
      RECENT ADVANCES: Histone mono-, di-, or tri-methylation at lysine residues result
      in either gene activation (H3K4, H3K36, and H3K79) or repression (H3K9, H3K27,
      and H3K20). Cross-talk occurs between various epigenetic marks on histones and
      DNA methylation. Both CS and oxidants alter histone acetylation/deacetylation and
      methylation/demethylation leading to enhanced proinflammatory gene expression.
      Chromatin modifications occur in lungs of patients with COPD. Histone deacetylase
      2 (HDAC2) reduction (levels and activity) is associated with steroid resistance
      in response to oxidative stress. CRITICAL ISSUES: Histone modifications are
      associated with DNA damage/repair and epigenomic instability as well as premature
      lung aging, which have implications in the pathogenesis of COPD. HDAC2/SIRTUIN1
      (SIRT1)-dependent chromatin modifications are associated with DNA damage-induced
      inflammation and senescence in response to CS-mediated oxidative stress. FUTURE
      DIRECTIONS: Understanding CS/oxidative stress-mediated chromatin modifications
      and the cross-talk between histone acetylation and methylation will demonstrate
      the involvement of epigenetic regulation of chromatin remodeling in inflammaging.
      This will lead to identification of novel epigenetic-based therapies against COPD
      and other smoking-related lung diseases. Pharmacological activation of
      HDAC2/SIRT1 or reversal of their oxidative post-translational modifications may
      offer therapies for treatment of COPD and CS-related diseases based on epigenetic
      histone modifications.

PMID- 22978697
TI  - Randomized, controlled clinical trial of bilayer ceramic and metal-ceramic crown
      performance.
AB  - PURPOSE: Analyzing the clinical performance of restorative materials is
      important, as there is an expectation that these materials and procedures will
      restore teeth and do no harm. The objective of this research study was to
      characterize the clinical performance of metal-ceramic crowns, core ceramic
      crowns, and core ceramic/veneer ceramic crowns based on 11 clinical criteria.
      MATERIALS AND METHODS: An IRB-approved, randomized, controlled clinical trial was
      conducted as a single-blind pilot study. The following three types of full crowns
      were fabricated: (1) metal-ceramic crown (MC) made from a Pd-Au-Ag-Sn-In alloy
      (Argedent 62) and a glass-ceramic veneer (IPS d.SIGN veneer); (2) non-veneered
      (glazed) lithium disilicate glass-ceramic crown (LDC) (IPS e.max Press core and
      e.max Ceram Glaze); and (3) veneered lithia disilicate glass-ceramic crown
      (LDC/V) with glass-ceramic veneer (IPS Empress 2 core and IPS Eris). Single-unit
      crowns were randomly assigned. Patients were recalled for each of 3 years and
      were evaluated by two calibrated clinicians. Thirty-six crowns were placed in 31
      patients. A total of 12 crowns of each of the three crown types were studied.
      Eleven criteria were evaluated: tissue health, marginal integrity, secondary
      caries, proximal contact, anatomic contour, occlusion, surface texture,
      cracks/chips (fractures), color match, tooth sensitivity, and wear (of crowns and
      opposing enamel). Numerical rankings ranged from 1 to 4, with 4 being excellent,
      and 1 indicating a need for immediate replacement. Statistical analysis of the
      numerical rankings was performed using a Fisher's exact test. RESULTS: There was
      no statistically significant difference between performance of the core ceramic
      crowns and the two veneered crowns at year 1 and year 2 (p > 0.05). All crowns
      were rated either as excellent or good for each of the clinical criteria;
      however, between years 2 and 3, gradual roughening of the occlusal surface
      occurred in some of the ceramic-ceramic crowns, possibly caused by dissolution
      and wear of the glaze. Statistically significant differences in surface texture
      (p= 0.0013) and crown wear (p= 0.0078) were found at year 3 between the metal
      ceramic crowns and the lithium-disilicate-based crowns. CONCLUSION: Based on the
      11 criteria, the clinical performance of ceramic-ceramic crowns was comparable to
      that of the metal-ceramic crowns after 2 years; however, gradual roughening
      occurred between years 2 and 3, which resulted in differences in surface texture
      and wear.

PMID- 22978698
TI  - One-pot synthesis of amides from aldehydes and amines via C-H bond activation.
AB  - A one-pot synthesis of amides from aldheydes with N-chloroamines, prepared in
      situ from amines, has been developed. Both aliphatic and aromatic aldehydes and
      many types of mono- and disubstituted amines are tolerant in this transformation.
      This cross-coupling reaction appears simple and convenient, has a wide substrate
      scope and makes use of cheap, abundant, and easily available reagents.

PMID- 22978699
TI  - Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment.
AB  - BACKGROUND: GAD65 (Glutamic acid decarboxylase 65 KDa isoform) is one of the most
      important auto-antigens involved in Type 1 diabetes induction. Although it serves
      as one of the first injury markers of beta-islets, the mechanisms governing GAD65
      expression remain poorly understood. Since the regulation of GAD65 is crucial for
      the proper functioning of insulin secreting cells, we investigated the stress
      induced regulation of GAD65 transcription. RESULTS: The present study shows that
      SMAR1 regulates GAD65 expression at the transcription level. Using a novel
      protein-DNA pull-down assay, we show that SMAR1 binding is very specific to GAD65
      promoter but not to the other isoform, GAD67. We show that Streptozotocin (STZ)
      mediated DNA damage leads to upregulation of SMAR1 and p53 expression, resulting
      in elevated levels of GAD65, in both cell lines as well as mouse beta-islets.
      SMAR1 and p53 act synergistically to up-regulate GAD65 expression upon STZ
      treatment. CONCLUSION: We propose a novel mechanism of GAD65 regulation by
      synergistic activities of SMAR1 and p53.

PMID- 22978701
TI  - Photoinduced dynamics of oxyluciferin analogues: unusual enol "super"photoacidity
      and evidence for keto-enol isomerization.
AB  - The first systematic pico-nanosecond time-resolved spectroscopic study of the
      firefly emitter oxyluciferin and two of its chemically modified analogues
      revealed that in the excited state the enol group is more acidic than the phenol
      group. The 6'-dehydroxylated derivative, in which only the 4-enolic hydroxyl
      proton is acidic, has an experimentally determined pK(a)* of 0.9 in dimethyl
      sulfoxide and an estimated pK(a)* of -0.3 in water. Moreover, this compound
      provided direct evidence that in a nonpolar, basic environment the keto form in
      the excited state can tautomerize into the enol, which subsequently undergoes
      excited-state proton transfer (ESPT) to produce enolate ion. This observation
      presents the first experimental evidence of excited-state keto-enol
      tautomerization of a firefly fluorophore, and it could be important in resolving
      the enol-keto conundrum related to the color-tuning mechanism of firefly
      bioluminescence. The 6'-dehydroxylated form of oxyluciferin adds a very rare case
      of a stable enol to the family of "super"photoacids.

PMID- 22978700
TI  - Aryl hydrocarbon receptor-dependence of dioxin's effects on constitutive mouse
      hepatic cytochromes P450 and growth hormone signaling components.
AB  - The aryl hydrocarbon receptor (AHR) has physiological roles in the absence of
      exposure to exogenous ligands, and mediates adaptive and toxic responses to the
      environmental pollutant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD). A readily
      metabolized AHR agonist, 3-methylcholanthrene, disrupts the expression of mouse
      hepatic growth hormone (GH) signaling components and suppresses cytochrome P450
      2D9 (Cyp2d9), a male-specific gene controlled by pulsatile GH via signal
      transducer and activator of transcription 5b (STAT5b). Using TCDD as an
      essentially nonmetabolized AHR agonist, and Ahr (-/-) mice as the preferred model
      to determine the AHR-dependence of biological responses, we now show that 2 mouse
      hepatic STAT5b target genes, Cyp2d9, and major urinary protein 2 (Mup2), are
      suppressed by TCDD in an AHR-dependent manner. TCDD also decreased hepatic mRNA
      levels for GH receptor, Janus kinase 2, and STAT5a/b with AHR-dependence. Without
      inducing selected hepatic inflammatory markers, TCDD caused AHR-dependent
      induction of Cyp1a1 and NADPH-cytochrome P450 oxidoreductase (Por) and
      suppression of Cyp3a11. In vehicle-treated mice, basal mRNA levels for CYP2D9,
      CYP3A11, POR, serum amyloid protein P, and MUP2 were influenced by Ahr genetic
      status. We conclude that AHR activation per se leads to dysregulation of hepatic
      GH signaling components and suppression of some, but not all, STAT5b target
      genes.

PMID- 22978702
TI  - Role of galactolipid biosynthesis in coordinated development of photosynthetic
      complexes and thylakoid membranes during chloroplast biogenesis in Arabidopsis.
AB  - The galactolipids monogalactosyldiacylglycerol (MGDG) and
      digalactosyldiacylglycerol (DGDG) are the predominant lipids in thylakoid
      membranes and indispensable for photosynthesis. Among the three isoforms that
      catalyze MGDG synthesis in Arabidopsis thaliana, MGD1 is responsible for most
      galactolipid synthesis in chloroplasts, whereas MGD2 and MGD3 are required for
      DGDG accumulation during phosphate (Pi) starvation. A null mutant of Arabidopsis
      MGD1 (mgd1-2), which lacks both galactolipids and shows a severe defect in
      chloroplast biogenesis under nutrient-sufficient conditions, accumulated large
      amounts of DGDG, with a strong induction of MGD2/3 expression, during Pi
      starvation. In plastids of Pi-starved mgd1-2 leaves, biogenesis of thylakoid-like
      internal membranes, occasionally associated with invagination of the inner
      envelope, was observed, together with chlorophyll accumulation. Moreover, the
      mutant accumulated photosynthetic membrane proteins upon Pi starvation,
      indicating a compensation for MGD1 deficiency by Pi stress-induced galactolipid
      biosynthesis. However, photosynthetic activity in the mutant was still abolished,
      and light-harvesting/photosystem core complexes were improperly formed,
      suggesting a requirement for MGDG for proper assembly of these complexes. During
      Pi starvation, distribution of plastid nucleoids changed concomitantly with
      internal membrane biogenesis in the mgd1-2 mutant. Moreover, the reduced
      expression of nuclear- and plastid-encoded photosynthetic genes observed in the
      mgd1-2 mutant under Pi-sufficient conditions was restored after Pi starvation. In
      contrast, Pi starvation had no such positive effects in mutants lacking
      chlorophyll biosynthesis. These observations demonstrate that galactolipid
      biosynthesis and subsequent membrane biogenesis inside the plastid strongly
      influence nucleoid distribution and the expression of both plastid- and nuclear
      encoded photosynthetic genes, independently of photosynthesis.

PMID- 22978703
TI  - Generating function approach to the calculation of spectral band shapes of free
      base chlorin including Duschinsky and Herzberg-Teller effects.
AB  - A generating function approach to the calculation of spectral band shapes
      including Duschinsky and Herzberg-Teller effects is proposed and applied to the
      computation of the free-base chlorin Q absorption bands, using molecular
      geometries and normal vibrations obtained by density functional theory
      computations. The results clearly show that non-Condon effects can significantly
      affect the relative intensities of the weakest Q(y) and, to a lesser extent, Q(x)
      bands. The proposed approach is extremely powerful and can be used in the cases
      where the molecular size makes the direct calculation of Franck-Condon integrals
      by recurrence formulas prohibitive.

PMID- 22978704
TI  - Capacity for NADPH regeneration in the leaves of two poplar genotypes differing
      in ozone sensitivity.
AB  - Cell capacity for cytosolic NADPH regeneration by NADP-dehydrogenases was
      investigated in the leaves of two hybrid poplar (Populus deltoides * Populus
      nigra) genotypes in response to ozone (O3 ) treatment (120 ppb for 17 days). Two
      genotypes with differential O3 sensitivity were selected, based on visual
      symptoms and fallen leaves: Robusta (sensitive) and Carpaccio (tolerant). The
      estimated O3 flux (POD0 ), that entered the leaves, was similar for the two
      genotypes throughout the treatment. In response to that foliar O3 flux, CO2
      assimilation was inhibited to the same extent for the two genotypes, which could
      be explained by a decrease in Rubisco (EC 4.1.1.39) activity. Conversely, an
      increase in PEPC (EC 4.1.1.31) activity was observed, together with the
      activation of certain cytosolic NADP-dehydrogenases above their constitutive
      level, i.e. NADP-G6PDH (EC 1.1.1.49), NADP-ME (malic enzyme) (EC 1.1.1.40) and
      NADP-ICDH (NADP-isocitrate dehydrogenase) (EC1.1.1.42). However, the activity of
      non-phosphorylating NADP-GAPDH (EC 1.2.1.9) remained unchanged. From the 11th
      fumigation day, NADP-G6PDH and NADP-ME profiles made it possible to differentiate
      between the two genotypes, with a higher activity in Carpaccio than in Robusta.
      At the same time, Carpaccio was able to maintain high levels of NADPH in the
      cells, while NADPH levels decreased in Robusta O3 -treated leaves. All these
      results support the hypothesis that the capacity for cells to regenerate the
      reducing power, especially the cytosolic NADPH pool, contributes to improve
      tolerance to high ozone exposure.

PMID- 22978705
TI  - Beliefs and practices during pregnancy and childbirth in urban slums of Dhaka,
      Bangladesh.
AB  - BACKGROUND: Worldwide urbanization has become a crucial issue in recent years.
      Bangladesh, one of the poorest and most densely-populated countries in the world,
      has been facing rapid urbanization. In urban areas, maternal indicators are
      generally worse in the slums than in the urban non-slum areas. The Manoshi
      program at BRAC, a non governmental organization, works to improve maternal,
      newborn, and child health in the urban slums of Bangladesh. This paper describes
      maternal related beliefs and practices in the urban slums of Dhaka and provides
      baseline information for the Manoshi program. METHODS: This is a descriptive
      study where data were collected using both quantitative and qualitative methods.
      The respondents for the quantitative methods, through a baseline survey using a
      probability sample, were mothers with infants (n = 672) living in the Manoshi
      program areas. Apart from this, as part of a formative research, thirty six in
      depth semi-structured interviews were conducted during the same period from two
      of the above Manoshi program areas among currently pregnant women who had also
      previously given births (n = 18); and recently delivered women (n = 18). RESULTS:
      The baseline survey revealed that one quarter of the recently delivered women
      received at least four antenatal care visits and 24 percent women received at
      least one postnatal care visit. Eighty-five percent of deliveries took place at
      home and 58 percent of the deliveries were assisted by untrained traditional
      birth attendants. The women mostly relied on their landladies for information and
      support. Members of the slum community mainly used cheap, easily accessible and
      available informal sectors for seeking care. Cultural beliefs and practices also
      reinforced this behavior, including home delivery without skilled assistance.
      CONCLUSIONS: Behavioral change messages are needed to increase the numbers of
      antenatal and postnatal care visits, improve birth preparedness, and encourage
      skilled attendance at delivery. Programs in the urban slum areas should also
      consider interventions to improve social support for key influential persons in
      the community, particularly landladies who serve as advisors and decision-makers.

PMID- 22978707
TI  - On the stability and morphology of complex coacervate core micelles: from
      spherical to wormlike micelles.
AB  - We present a systematic study of the stability and morphology of complex
      coacervate core micelles (C3Ms) formed from poly(acrylic acid) (PAA) and poly(N
      methyl-2-vinylpyridinium)-b-poly(ethylene oxide) (PM2VP-b-PEO). We use polarized
      and depolarized dynamic and static light scattering, combined with small-angle X
      ray scattering, to investigate how the polymer chain length and salt
      concentration affect the stability, size, and shape of these micelles. We show
      that C3Ms are formed in aqueous solution below a critical salt concentration,
      which increases considerably with increasing PAA and PM2VP length and levels off
      for long chains. This trend is in good agreement with a mean-field model of
      polyelectrolyte complexation based on the Voorn-Overbeek theory. In addition, we
      find that salt induces morphological changes in C3Ms when the PAA homopolymer is
      sufficiently short: from spherical micelles with a diameter of several tens of
      nanometers at low salt concentration to wormlike micelles with a contour length
      of several hundreds of nanometers just before the critical salt concentration. By
      contrast, C3Ms of long PAA homopolymers remain spherical upon addition of salt
      and shrink slightly. A critical review of existing literature on other C3Ms
      reveals that the transition from spherical to wormlike micelles is probably a
      general phenomenon, which can be rationalized in terms of a classical packing
      parameter for amphiphiles.

PMID- 22978706
TI  - Validation of a cheap and simple nondestructive method for obtaining AFLPs and
      DNA sequences (mitochondrial and nuclear) in amphibians.
AB  - The use of nondestructive methods for obtaining DNA from amphibians (e.g. buccal
      swabs) allows genetic studies to be performed without affecting the survival of
      the studied individuals. In this study, we compared two methods of nondestructive
      DNA sampling, buccal swabs and interdigital membrane or toe-clipping, in several
      amphibian species of different size: Rhinella spinulosa, R. atacamensis, six
      species of the genus Telmatobius and Pleurodema thaul. We evaluated the integrity
      of the DNA extracted by sequencing fragments of mitochondrial and nuclear genes
      and by generating amplified fragment length polymorphisms markers (AFLPs). In all
      cases, we obtained an adequate amount of DNA (mean range 55-298 ng/MUL). We
      obtained identical DNA sequences from buccal swab and interdigital membrane/toe
      clip for all individuals. The differences in the coding of AFLP markers between
      the tissues were similar to those reported for replicas of the same type of
      sample in similar analyses in other species of amphibians. In conclusion, the use
      of buccal swabs is a trustworthy and inexpensive method to obtain DNA for
      mitochondrial and nuclear sequencing and AFLP analyses. Given the types of
      markers evaluated, buccal swabs may be used for phylogenetic, phylogeographic and
      population genetic studies, even in small amphibians (<33 mm).

PMID- 22978708
TI  - Ligand binding to heme proteins: a comparison of cytochrome c variants with
      globins.
AB  - We have studied the binding of carbon monoxide (CO) in mutants of Cyt c having
      its methionine at position 80 replaced by alanine, aspartate, and arginine, so
      that the sixth coordination is available for ligand binding. We have employed
      Fourier transform infrared (FTIR) photolysis difference spectroscopy to examine
      interactions of the heme-bound and photolyzed CO (and also nitric oxide, NO) in
      the small heme pocket created by the mutations. By using FTIR temperature
      derivative spectroscopy (TDS) and nanosecond flash photolysis, the enthalpy
      barrier distributions for CO rebinding were determined. In flash photolysis
      experiments, the majority of ligands rebind to the heme iron on picosecond time
      scales so that only the high-barrier tail of the distributions is visible on the
      nanosecond scale. By continuous wave excitation prior to TDS characterization of
      the barriers, however, each Cyt c molecule is photoexcited multiple times and
      complete photodissociation can be achieved, which likely arises from a rotation
      of the CO within the heme pocket so that the oxygen faces the heme iron.
      Apparently, reorientation prior to rebinding constitutes an additional and
      significant contribution to the rebinding barrier. Our experiments reveal that
      the compact, rigid structure of Cyt c offers no alternative binding sites for
      photodissociated ligands in the protein matrix. A comparison of ligand binding in
      these Cyt c mutants and hemoglobins underscores the importance of internal ligand
      docking sites and ligand migration routes for conveying a ligand binding function
      to heme proteins.

PMID- 22978709
TI  - Re-appraisal of negative emotions in cocaine dependence: dysfunctional
      corticolimbic activation and connectivity.
AB  - Cocaine dependence is associated with pronounced elevations of negative affect
      and deficient regulation of negative emotions. We aimed to investigate the neural
      substrates of negative emotion regulation in cocaine-dependent individuals (CDI),
      as compared to non-drug-using controls, using functional magnetic resonance
      imaging (fMRI) during a re-appraisal task. Seventeen CDI abstinent for at least
      15 days and without other psychiatric co-morbidities and 18 intelligence quotient
      matched non-drug-using controls participated in the study. Participants performed
      the re-appraisal task during fMRI scanning: they were exposed to 24 blocks of
      negative affective or neutral pictures that they should Observe (neutral
      pictures), Maintain (sustain the emotion elicited by negative pictures) or
      Suppress (regulate the emotion elicited by negative pictures through previously
      trained re-appraisal techniques). Task-related activations during two conditions
      of interest (Maintain>Observe and Suppress>Maintain) were analyzed using the
      general linear model in SPM8 software. We also performed psychophysiological
      interaction (PPI) seed-based analyses based on one region from each condition:
      the dorsolateral prefrontal cortex (dlPFC-Maintain>Observe) and the inferior
      frontal gyrus (IFG-Suppress>Maintain). Results showed that cocaine users had
      increased right dlPFC and bilateral temporoparietal junction activations during
      Maintain>Observe, whereas they showed decreased right IFG, posterior cingulate
      cortex, insula and fusiform gyrus activations during Suppress>Maintain. PPI
      analyses showed that cocaine users had increased functional coupling between the
      dlPFC and emotion-related regions during Maintain>Observe, whereas they showed
      decreased functional coupling between the right IFG and the amygdala during
      Suppress>Maintain. These findings indicate that CDI have dysfunctional
      corticolimbic activation and connectivity during negative emotion experience and
      re-appraisal. 

PMID- 22978710
TI  - Growth of ligand-target interaction data in ChEMBL is associated with increasing
      and activity measurement-dependent compound promiscuity.
AB  - Compounds with high-confidence target annotations and activity measurements in
      the original and current release of the ChEMBL database have been compared to
      better understand how the growth of compound activity data might influence the
      spectrum of ligand-target interactions and the degree of target promiscuity among
      active compounds. Compared to the original ChEMBL release, a significant increase
      in the proportion of target promiscuous compounds was observed in the current
      version. The presence of these compounds led to large-magnitude changes in
      compound activity-based target and target family relationships and to a
      reorganization of major target communities. Surprisingly, however, this strong
      trend toward increasing target promiscuity was largely caused by growth of
      compounds with exclusive IC(50) measurements. By contrast, compounds with
      available equilibrium constants, which were also added in large amounts, did not
      substantially alter compound-based target relationships and notably contribute to
      increasing target promiscuity. These findings suggest that apparent compound
      promiscuity is much dependent on experimental conditions under which activities
      are determined and that care should be taken when evaluating promiscuity and
      polypharmacology on the basis of assay-dependent activity measurements.

PMID- 22978711
TI  - Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.
AB  - We sought to identify the molecular basis of the autosomal dominant form of Kufs
      disease, an adult onset form of neuronal ceroid lipofuscinosis. We used a
      combination of classic linkage analysis and Next Generation Sequencing to map and
      identify mutations in DNAJC5 in a total of three families. We analyzed the
      clinical manifestations in 20 individuals with mutation in DNAJC5. We report here
      the mapping and the identification of a p.L116del mutation in DNAJC5 segregating
      with the disease in two distinct American families, as well as a p.L115R mutation
      in an additional family. The age of onset and clinical manifestations were very
      homogeneous among mutation positive individuals, including generalized tonic
      clonic seizures, myoclonus, ataxia, speech deterioration, dementia, and premature
      death. A few individuals also exhibited parkinsonism. DNAJC5, which encodes the
      cysteine string protein (CSPalpha), a presynaptic protein implicated in
      neurodegeneration, causes autosomal dominant Kufs disease. The leucine residues
      at positions 115 and 116 are hotspots for mutations and result in a homogeneous
      phenotype of progressive myoclonus epilepsy with onset around 30 years old.

PMID- 22978712
TI  - Lycopene counteracts the hepatic response to 7,12-dimethylbenz[a]anthracene by
      altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers.
AB  - CONTEXT: Lycopene is a carotenoid found in tomato, watermelon, pink grapefruit,
      and guava in high concentration. Dietary intake of lycopene has been proposed to
      inversely correlate with the risk of cancer. It has also been reported to provide
      protection against cellular damage caused by reactive oxygen species, which makes
      it worthwhile to study the effect of lycopene on liver damage in rat model.
      OBJECTIVE: In this study, we report the effect of lycopene on 7,12
      dimethylbenz[a]-anthracene (DMBA)-induced expression of Bax, Bcl-2, caspases, and
      oxidative stres biomarkers in the liver. MATERIALS AND METHODS: Lycopene was
      administered orally at 20 mg/kg body weight for 20 weeks followed by the
      intraperitoneal injection of DMBA (50 mg/kg body weight) on day 1 and day 30 of
      the experiment. Control rats received vehicle (olive oil) or DMBA alone. Rats
      were sacrificed after completion of the treatment. RESULTS: We observed that the
      levels of Bax, caspase-3, and caspase-9 decreased to 44, 67, and 43%,
      respectively, and Bcl-2 increased by 80% in DMBA-treated rats. Lycopene reversed
      the changes in the respective groups, and decreased the level of Bcl-2 to 25%,
      while increasing the Bax to 42% when compared to DMBA control. Lycopene increased
      the expression of caspase-3 (82.09%) and caspase-9 (58.96%), and attenuated the
      level of hepatic malondialdehyde (41%) and 8-isoprostane (40%) when compared to
      the respective controls. Glutathione (GSH) decreased significantly in DMBA group
      (15.89%), but reached the normal level in lycopene-treated animals. Hepatic
      lycopene concentration in treated rats was 8.2 nmol/g tissue. CONCLUSION: The
      study reports that lycopene counteracts the hepatic response to DMBA by altering
      the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers in animal
      model.

PMID- 22978714
TI  - Direct bandgap materials based on the thin films of SexTe100 - x nanoparticles.
AB  - In this study, we fabricated thin films of SexTe100 - x (x = 0, 3, 6, 9, 12, and
      24) nanoparticles using thermal evaporation technique. The results obtained by X
      ray diffraction show that the as-synthesized nanoparticles have polycrystalline
      structure, but their crystallinity decreases by increasing the concentration of
      Se. They were found to have direct bandgap (Eg), whose value increases by
      increasing the Se content. These results are completely different than those
      obtained in the films of SexTe100 - x microstructure counterparts.
      Photoluminescence and Raman spectra for these films were also demonstrated. The
      remarkable results obtained in these nanoparticles specially their controlled
      direct bandgap might be useful for the development of optical disks and other
      semiconductor devices.

PMID- 22978713
TI  - Methods for detection of mitochondrial and cellular reactive oxygen species.
AB  - SIGNIFICANCE: Mitochondrial and cellular reactive oxygen species (ROS) play
      important roles in both physiological and pathological processes. Different ROS,
      such as superoxide (O2(*-)), hydrogen peroxide, and peroxynitrite (ONOO(-)),
      stimulate distinct cell-signaling pathways and lead to diverse outcomes depending
      on their amount and subcellular localization. A variety of methods have been
      developed for ROS detection; however, many of these methods are not specific, do
      not allow subcellular localization, and can produce artifacts. In this review, we
      will critically analyze ROS detection and present advantages and the shortcomings
      of several available methods. RECENT ADVANCES: In the past decade, a number of
      new fluorescent probes, electron-spin resonance approaches, and immunoassays have
      been developed. These new state-of-the-art methods provide improved selectivity
      and subcellular resolution for ROS detection. CRITICAL ISSUES: Although new
      methods for HPLC superoxide detection, application of fluorescent boronate
      containing probes, use of cell-targeted hydroxylamine spin probes, and immunospin
      trapping have been available for several years, there has been lack of
      translation of these into biomedical research, limiting their widespread use.
      FUTURE DIRECTIONS: Additional studies to translate these new technologies from
      the test tube to physiological applications are needed and could lead to a wider
      application of these approaches to study mitochondrial and cellular ROS.

PMID- 22978716
TI  - Extraperitoneal resection of the right colon for locally advanced colon cancer.
AB  - AIM: Optimal colon cancer surgery correlates with a reduction in recurrence rate
      and improved overall prognosis. This technical note describes the extraperitoneal
      approach for locally advanced right colon cancer. METHOD: The retroperitoneal
      technique, mainly used in pseudomyxoma peritonei resectional surgery, is
      described in three surgical steps and it is compared with existing surgical
      approaches for right colon cancer. RESULTS: This approach has the advantages of
      early entry in the retroperitoneal plane well away from the tumour, early
      recognition and protection of the ureter and minimal manipulation of the tumour
      bearing right colon. CONCLUSION: Extraperitoneal resection of the right colon for
      locally advanced colon cancer is technically feasible, safe and achieves tumour
      free retroperitoneal margins.

PMID- 22978717
TI  - Evaluating the peripheral optical effect of multifocal contact lenses.
AB  - PURPOSE: Multifocal soft contact lenses have been used to decrease the
      progression of myopia, presumably by inducing relative peripheral myopia at the
      same time as the central image is focused on the fovea. The aim of this study was
      to investigate how the peripheral optical effect of commercially available
      multifocal soft contact lenses can be evaluated from objective wavefront
      measurements. METHODS: Two multifocal lenses with high and low add and one
      monofocal design were measured over the +/-40 degrees  horizontal field, using a
      scanning Hartmann-Shack wavefront sensor on four subjects. The effect on the
      refractive shift, the peripheral image quality, and the depth of field of the
      lenses was evaluated using the area under the modulation transfer function as the
      image quality metric. RESULTS: The multifocal lenses with a centre distance
      design and 2 dioptres of add induced about 0.50 dioptre of relative peripheral
      myopia at 30 degrees  in the nasal visual field. For larger off-axis angles the
      border of the optical zone of the lenses severely degraded image quality.
      Moreover, these multifocal lenses also significantly reduced the image quality
      and increased the depth of field for angles as small as 10 degrees -15 degrees .
      CONCLUSIONS: The proposed methodology showed that the tested multifocal soft
      contact lenses gave a very small peripheral myopic shift in these four subjects
      and that they would need a larger optical zone and a more controlled depth of
      field to explain a possible treatment effect on myopia progression.

PMID- 22978715
TI  - The impact of serum lipids on risk for microangiopathy in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Few large-scale, real-world studies have assessed the relative
      associations of lipid fractions with diabetic microvascular events. The main
      objective of this study was to evaluate the association of the lipid profile
      components, high density lipoprotein cholesterol (HDL-C), low density lipoprotein
      cholesterol (LDL-C), triglycerides (TG), and non-high density lipoprotein
      cholesterol (non-HDL-C) with microvascular complications (MVCs) in type 2
      diabetes mellitus (T2DM) patients. METHODS: This observational cohort study
      queried the HealthCore Integrated Research Database (HIRDSM) for newly-diagnosed
      (Index Date) 18-64-year-old patients with diabetes mellitus between 01/01/2005
      06/30/2010. Inclusion required >= 12 months pre-index continuous health plan
      eligibility and >= 1 pre-index lipid profile result. Patients with polycystic
      ovary syndrome and prior MVCs were excluded. Incident complications were defined
      as the earliest occurrence of diabetic retinopathy, peripheral neuropathy, and/or
      nephropathy post-index. Cox proportional models and Kaplan-Meier (KM) curves were
      used to evaluate associations among variables. RESULTS: Of the patients
      (N=72,267), 50.05% achieved HDL-C, 64.28% LDL-C, 59.82% TG, and 56.79% non-HDL-C
      American Diabetes Association goals at baseline. During follow-up (mean, 21.74
      months), there were 5.21 microvascular events per 1,000 patient-months. A 1-mg/dL
      increase in HDL-C was associated with 1% decrease in any MVC risk (P< .0001), but
      for LDL-C, TG, and non-HDL-C, 1-mg/dL increase resulted in increases of 0.2% (P<
      .0001), 0.1% (P<0.001) and 0.3% (P<0.001) in MVC risk. Patients achieving HDL-C
      goals had a 11% lower risk of MVC versus non-achievers (RR 0.895, [95% CI, 0.852
      0.941], P< .0001). Similarly, TG goal attainment was associated with a lowered
      risk for any MVC (RR 0.849, [95% CI, 0.808-0.892], P< .0001). Evaluation of KM
      survival curves demonstrated no significant difference in the risk of MVCs
      between patients achieving vs. not achieving LDL-C goals, but did demonstrate a
      difference in MVC risk between patients achieving vs. not achieving non-HDL-C
      goals. CONCLUSION: This study demonstrates significant independent associations
      among lipid fractions and risk for microangiopathy. These findings suggest that
      attaining established ADA goals for HDL-C, TG, and non-HDL-C may reduce risk for
      microvascular events among patients with diabetes.

PMID- 22978719
TI  - Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) in a population of young
      adults: relations to cardiovascular risk markers and carotid artery intima-media
      thickness. The Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVES: The tissue inhibitor of metalloproteinases 4 (TIMP4) is present in
      significant amounts in human atherosclerotic coronary artery lesions, but its
      relations with the early pathogenesis of atherosclerotic changes have not been
      clarified. We studied the associations of circulating TIMP4 with pre-clinical
      markers of atherosclerosis and traditional cardiovascular risk factors by using
      longitudinal data on carotid artery intima-media (cIMT) thickness in a population
      based cohort of asymptomatic young adult Finns. METHODS: Data on cIMT, plasma
      TIMP4, lipids, CRP, blood pressure, BMI, smoking status and daily alcohol intake
      were obtained from 980 24-39 year-old participants in 2001. The 6-year follow-up
      in cIMT measurements were performed in 2007 for 769 participants. RESULTS: Plasma
      TIMP4 concentrations (mean +/- SD) were 2.3 +/- 1.7 ng/mL in men and 2.5 +/- 1.8
      ng/mL in women. Age, LDL-cholesterol, BMI and systolic blood pressure were
      directly associated with TIMP4 concentration. In a multivariable model, the
      independent determinants of TIMP4 included systolic blood pressure (p = 0.008)
      and daily smoking (p = 0.009), both being inversely associated with TIMP4. These
      two baseline variables explained 1.5% of the variation in TIMP4. TIMP4 was
      significantly and inversely associated with cIMT measured 6 years later (beta =-
      0.0135, p = 0.01) explaining 0.7% of the variability of cIMT. CONCLUSION: In
      young apparently healthy adults, circulating TIMP4 concentration was
      independently and inversely associated with cIMT, a marker of vascular structure
      and function.

PMID- 22978720
TI  - In vitro and clinical studies examining the expression of osteopontin in
      cigarette smoke-exposed endothelial cells and cigarette smokers.
AB  - BACKGROUND: Cigarette smoking is a leading cause of mortality and morbidity and
      is associated with cardiovascular disease via contributory processes such as
      endothelial dysfunction, inflammation and thrombosis. Cigarette smoke both
      contains and stimulates the production of cellular oxidants and it may also
      promote vascular inflammation. Osteopontin is a non-collagenous matrix protein
      first identified in bone and there is increasing evidence for its role in
      inflammation and cardiovascular disease via its action as a soluble cytokine.
      METHODS: In this study we have examined the mechanisms underlying the expression
      of osteopontin in human vascular endothelial cells in vitro following exposure to
      cigarette smoke particulate matter (PM), using PCR, electrochemiluminescence,
      immunostaining and Western blotting. We further determined if serum osteopontin
      levels changed in humans who quit smoking. RESULTS: Non-cytotoxic concentrations
      of PM increased osteopontin levels in cultured human endothelial cells and this
      effect was reduced in the presence of ascorbate, suggesting a role for oxidants
      in the response to PM. However, oxidant production played no role in the PM
      evoked induction MMP-3, an enzyme which cleaves osteopontin. In smokers who quit
      smoking for 5 days, serum osteopontin levels were significantly lowered compared
      to those measured prior to smoking cessation. CONCLUSIONS: In vitro cigarette
      smoke extract exposure induced osteopontin expression in human endothelial cells
      in an oxidative stress-dependent manner, which may involve MMP-3 cleavage. In
      humans, serum osteopontin was decreased with short-term smoking cessation.
      Endothelial-derived osteopontin may contribute to inflammation in smokers, and
      may also contribute to atherosclerosis and cardiovascular disease-related
      processes.

PMID- 22978721
TI  - Semiquantification of ATP in live cells using nonspecific desorption of DNA from
      graphene oxide as the internal reference.
AB  - In this aritcle, we have developed an interesting imaging method for
      intracellular ATP molecules with semiquantitation. While there has been a lot of
      work in understanding intracellular events, very few can come close to
      quantitation or semiquantitation in living cells. In this work, we made an
      effective use of nanomaterials, graphene oxides, both as a quencher and a carrier
      for intracellular delivery. In addition, this graphene oxide also serves as the
      carrier for reference probes for fluorescent imaging. An ATP aptamer molecular
      beacon (AAMB) is adsorbed on graphene oxide (GO) to form a double quenching
      platform. The AAMB/GO spontaneously enters cells, and then AAMB is released and
      opened by intracellular ATP. The resulting fluorescence recovery is used to
      perform ATP live-cell imaging with greatly improved background and signaling.
      Moreover, a control ssDNA, which is released nonspecifically from GO by nontarget
      cellular proteins, can serve as an internal reference for ATP semiquantification
      inside living cells using the intensity ratio of the AAMB and control. This
      approach can serve as a way for intracellular delivery and quantitative analysis.

PMID- 22978723
TI  - High-amplitude pace mapping increases safety of radiofrequency catheter ablation
      of parahisian ectopic foci.
AB  - BACKGROUND: The objective of the study is to assess the efficacy of high
      amplitude pace mapping in terms of the atrioventricular (AV) block risk after
      radiofrequency catheter ablation (RCA) of parahisian ectopic foci. METHODS:
      Twenty patients aged 38 +/- 14 years with no structural heart disease underwent
      RCA of parahisian ectopic foci. All the patients were randomized into two groups:
      Group I (n = 11) had RCA performed in the region defined as ectopic focus by
      electrophysiology study and Group II (n = 9) had high-amplitude pacing performed
      in the region of "perfect" mapping. RCA was done only at the sites where high
      amplitude pacing revealed the absence of His bundle capture. RESULTS: In group I,
      the efficacy of RCA was 54.5% and it was 100% in group II (P = 0.0195). Group II
      had no complications; in group I there were 27% of AV blocks (P = 0.0893). The
      late recurrence of ectopic activity was comparable in both groups: 3 (27%) and 2
      (22%), respectively (P = 0.7953). In all the cases of recurrent ectopic activity
      and in all the cases of ineffective primary procedure, group I had effective
      reablation procedures performed using high-amplitude pace mapping. The overall
      efficacy in terms of repeated procedures was 90%. CONCLUSION: High-amplitude pace
      mapping increases primary and secondary efficacy of parahisian ectopic foci RCA
      and decreases the risk of AV block development. (PACE 2012;35:1458-1463).

PMID- 22978722
TI  - A systematic review of hand hygiene improvement strategies: a behavioural
      approach.
AB  - BACKGROUND: Many strategies have been designed and evaluated to address the
      problem of low hand hygiene (HH) compliance. Which of these strategies are most
      effective and how they work is still unclear. Here we describe frequently used
      improvement strategies and related determinants of behaviour change that prompt
      good HH behaviour to provide a better overview of the choice and content of such
      strategies. METHODS: Systematic searches of experimental and quasi-experimental
      research on HH improvement strategies were conducted in Medline, Embase, CINAHL,
      and Cochrane databases from January 2000 to November 2009. First, we extracted
      the study characteristics using the EPOC Data Collection Checklist, including
      study objectives, setting, study design, target population, outcome measures,
      description of the intervention, analysis, and results. Second, we used the
      Taxonomy of Behavioural Change Techniques to identify targeted determinants.
      RESULTS: We reviewed 41 studies. The most frequently addressed determinants were
      knowledge, awareness, action control, and facilitation of behaviour. Fewer
      studies addressed social influence, attitude, self-efficacy, and intention.
      Thirteen studies used a controlled design to measure the effects of HH
      improvement strategies on HH behaviour. The effectiveness of the strategies
      varied substantially, but most controlled studies showed positive results. The
      median effect size of these strategies increased from 17.6 (relative difference)
      addressing one determinant to 49.5 for the studies that addressed five
      determinants. CONCLUSIONS: By focussing on determinants of behaviour change, we
      found hidden and valuable components in HH improvement strategies. Addressing
      only determinants such as knowledge, awareness, action control, and facilitation
      is not enough to change HH behaviour. Addressing combinations of different
      determinants showed better results. This indicates that we should be more
      creative in the application of alternative improvement activities addressing
      determinants such as social influence, attitude, self-efficacy, or intention.

PMID- 22978724
TI  - Recent contributions in the field of the recombinant expression of disulfide
      bonded proteins in bacteria.
AB  - The production of heterologous disulfide bonded proteins in bacteria remains a
      biotechnological challenge. A rapid literature survey results in the
      identification of some interesting proposals, such as the option of producing
      functional proteins in the cytoplasm in the presence of sulfhydryl oxidases and
      isomerases. Furthermore, an ever-increasing number of applications refers to
      recombinant proteins displayed at the bacterial surface. Time will tell whether
      these developments will lead to universally accepted laboratory protocols.

PMID- 22978725
TI  - Validation of a clinical prediction model for early admission to the intensive
      care unit of patients with pneumonia.
AB  - OBJECTIVES: The Risk of Early Admission to the Intensive Care Unit (REA-ICU)
      index is a clinical prediction model that was derived based on 4,593 patients
      with community-acquired pneumonia (CAP) for predicting early admission to the
      intensive care unit (ICU; i.e., within 3 days following emergency department [ED]
      presentation). This study aimed to validate the REA-ICU index in an independent
      sample. METHODS: The authors retrospectively stratified 850 CAP patients enrolled
      in a multicenter prospective randomized trial conducted in Switzerland, using the
      REA-ICU index, alternate clinical prediction models of severe pneumonia (SMART
      COP, CURXO-80, and the 2007 IDSA/ATS minor severity criteria), and pneumonia
      severity assessment tools (the Pneumonia Severity Index [PSI] and CURB-65).
      RESULTS:   The rate of early ICU admission did not differ between the validation
      and derivation samples within each risk class of the REA-ICU index, ranging from
      1.1% to 1.8% in risk class I to 27.1% to 27.6% in risk class IV. The areas under
      the receiver operating characteristic (ROC) curve were 0.76 (95% confidence
      interval [CI] = 0.70 to 0.83) and 0.80 (95% CI = 0.77 to 0.83) in the validation
      and derivation samples, respectively. In the validation sample, the REA-ICU index
      performed better than the pneumonia severity assessment tools, but failed to
      demonstrate an accuracy advantage over alternate prediction models in predicting
      ICU admission. CONCLUSIONS: The REA-ICU index reliably stratifies CAP patients
      into four categories of increased risk for early ICU admission within 3 days
      following ED presentation. Further research is warranted to determine whether
      inflammatory biomarkers may improve the performance of this clinical prediction
      model.

PMID- 22978726
TI  - Failure of prospective validation and derivation of a refined clinical decision
      rule for chest radiography in emergency department patients with chest pain and
      possible acute coronary syndrome.
AB  - OBJECTIVES: The authors previously derived a clinical decision rule (CDR) for
      chest radiography in patients with chest pain and possible acute coronary
      syndrome (ACS) consisting of the absence of three predictors: history of
      congestive heart failure, history of smoking, and abnormalities on lung
      auscultation. The aim of the investigation was to prospectively validate and
      refine the CDR for chest radiography in an independent patient population.
      METHODS: Patients over 24 years of age with a primary complaint of chest pain and
      possible ACS were prospectively enrolled from September 2008 to January 2010 at
      an academic emergency department (ED) with 73,000 annual patient visits.
      Physicians completed standardized data collection forms before ordering chest
      radiographs. Two investigators, blinded to the data collection forms,
      independently classified chest radiographs as "normal,""abnormal not requiring
      intervention," or "abnormal requiring intervention" (e.g., heart failure,
      infiltrates), based on review of the radiology report and medical record.
      Analyses included descriptive statistics, interrater reliability assessment
      (kappa), and recursive partitioning. RESULTS: Of 1,159 visits for possible ACS in
      which chest radiography was obtained, mean (+/-SD) age was 60.3 (+/-15.6) years,
      and 51% were female. Twenty-four percent had a history of acute myocardial
      infarction, 10% congestive heart failure, and 11% atrial fibrillation. Sixty-nine
      (6.0%, 95% confidence interval [CI] = 4.7% to 7.5%) patients had a radiographic
      abnormality requiring intervention. The kappa statistic for chest radiograph
      classification was 0.93 (95% CI = 0.88 to 0.97). The previously derived
      prediction rule (no history of congestive heart failure, no history of smoking,
      and no abnormalities on lung auscultation) was 78.3% sensitive (95% CI = 67.2% to
      86.4%) and 45.1% specific (95% CI = 42.2% to 48.1%) and had a positive predictive
      value of 8.3% (95% CI = 6.4% to 10.7%) and a negative predictive value of 97.0%
      (95% CI = 95.2% to 98.2%). Due to suboptimal performance, the rule was refined.
      The refined rule (no shortness of breath, no history of smoking, no abnormalities
      on lung auscultation, and age < 55 years) was 100.0% sensitive (95% CI = 93.4% to
      100.0%) and 11.5% specific (95% CI = 9.6% to 13.5%) and had a positive predictive
      value of 6.7% (95% CI = 5.3% to 8.4%) and a negative predictive value of 100.0%
      (95% CI = 96.3% to 100.0%). CONCLUSIONS: Prospective validation of our previously
      derived CDR for clinically important chest radiographic abnormalities was not
      successful. Derivation of a refined rule identified all clinically important
      radiographic abnormalities, but was insufficiently specific. No CDR with adequate
      sensitivity and specificity could be found.

PMID- 22978727
TI  - Prevalence of acute lung injury among medical patients in the emergency
      department.
AB  - BACKGROUND: Acute lung injury (ALI) affects an estimated 190,000 persons per year
      in U.S. intensive care units (ICUs), but little is known about its prevalence in
      the emergency department (ED). OBJECTIVES: The objective was to describe the
      prevalence of ALI among mechanically ventilated adult nontrauma patients in the
      ED. The hypothesis was that the prevalence of ALI in adult ED patients would be
      low. METHODS: This was a retrospective cohort study of admitted nontrauma
      patients presenting to an academic ED. Two trained investigators abstracted data
      from patient records using a standardized form. The use of mechanical ventilation
      in the ED was identified in two phases. First, all ED patients were screened for
      the current procedural terminology (CPT) code for endotracheal intubation (CPT
      31500) from January 1, 2003, to December 31, 2006. Second, each patient record
      was reviewed to verify the use of mechanical ventilation. ALI was defined in
      accordance with a modified version of the American-European Consensus Conference
      criteria as: 1) hypoxemia defined as PaO(2) /FiO(2) ratio <=300 mm Hg on all
      arterial blood gases (ABGs) in the ED and the first 24 hours of admission, 2) the
      presence of bilateral infiltrates on chest radiograph, and 3) the absence of left
      atrial hypertension. Data are presented in absolute numbers and percentages.
      Interobserver agreement was evaluated using the kappa statistic. RESULTS: Of the
      552 patients who received mechanical ventilation in the ED and were subsequently
      admitted, a total of 134 (24.3%, 95% confidence interval [CI] = 20.8% to 28.0%)
      met hypoxemia criteria. Of these, 34 had evidence of left atrial hypertension, 52
      did not have chest radiograph findings consistent with ALI, and two did not have
      a chest radiograph performed; the remaining 46 met ALI criteria. An additional
      two patients who died in the ED had clinical evidence of ALI. Thus, 48 of 552, or
      8.7% (95% CI = 6.6% to 11.3%), met criteria for ALI. The kappa value for
      determination of ALI was 0.84 (95% CI = 0.54 to 1.0). CONCLUSIONS: The prevalence
      of ALI was nearly 9% in adult nontrauma patients receiving mechanical ventilation
      in the ED. Further study is required to determine which types of patients present
      to the ED with ALI, the extent to which lung protective ventilation is used, and
      the need for ED ventilator management algorithms.

PMID- 22978728
TI  - Practice patterns in asthma discharge pharmacotherapy in pediatric emergency
      departments: a pediatric emergency research Canada study.
AB  - OBJECTIVES: The objective was to examine utilization of beta2 agonists via
      metered dose inhalers with oral and inhaled corticosteroids (ICS) at discharge in
      children with acute asthma. METHODS: This was a retrospective medical record
      review at six pediatric emergency departments (EDs) of otherwise healthy children
      2 to 17 years of age discharged with acute asthma. Data were extracted on
      history, disease severity, and pharmacotherapy used in the ED and at discharge.
      The primary outcome was the proportion of children prescribed "comprehensive
      therapy," i.e., albuterol via metered dose inhaler (MDI) with oral and ICS.
      RESULTS: The overall rate of comprehensive therapy was 382 of 654 (58%), which
      varied from 30% to 84% (p < 0.0001). A total of 570 of 575 children discharged on
      albuterol received MDIs. Although the rates of prescriptions for oral and ICS
      were both 80%, only 58% of patients without ICS on arrival were offered ICS at
      discharge. There was significant variation in the rates of all discharge
      pharmacotherapies across centers. The independent predictors of comprehensive
      therapy were daytime presentation (odds ratio [OR] = 1.67, 95% confidence
      interval [CI] = 1.05 to 2.67) and "intensive stabilization" (OR = 2.33, 95% CI =
      1.29 to 2.67). Seventeen patients (2.6%) were prescribed antibiotics. Children
      were more likely to receive antibiotics if they had moderate to severe
      exacerbations (OR = 2.8) or received a chest radiograph (OR = 8.4). CONCLUSIONS:
      The overwhelming majority of children discharged from Canadian pediatric EDs with
      acute asthma are prescribed inhaled albuterol via MDIs. Although the
      corticosteroid use at discharge is higher than previously reported, utilization
      of new prescriptions for ICS may not be optimal. Children presenting during
      daytime to EDs receiving intensive stabilization are more likely to receive the
      albuterol/oral steroid/ICS combination.

PMID- 22978729
TI  - Observational study of telephone consults by stroke experts supporting community
      tissue plasminogen activator delivery.
AB  - OBJECTIVES: Barriers to intravenous (IV) tissue plasminogen activator (tPA) use
      in ischemic stroke include limited treatment experience of community physicians.
      Models of acute stroke care have been designed to address these limitations by
      providing community support. These include support by telephone or televideo,
      with or without subsequent transport to tertiary care centers. The authors
      describe the frequency, characteristics, and effect of community phone
      consultations to a 24/7 stroke "hotline" staffed by stroke physicians at an
      academic stroke center using such a model. METHODS: Twelve intervention hospitals
      participating in the INcreasing Stroke Treatment through Interventional behavior
      Change Tactics (INSTINCT) trial were provided a single-access number ("hotline")
      for expert consultation on tPA use. Experts consisted of stroke-trained
      physicians at an academic medical center. Hotline use was not mandated by the
      study protocol, nor was patient transfer required. Consultants were required to
      record all treatment questions in a Web-based log. All patients discussed over
      the hotline and/or treated with tPA in an INSTINCT hospital underwent multilevel
      chart review by trained nurse coordinators. Cases were linked to logged hotline
      calls, based on the time of treatment and the initial treating hospital.
      Physician adjudicators assessed appropriateness of tPA treatment, presence of
      deviation from standard guidelines, and treatment complications (intracranial
      hemorrhage [ICH], systemic hemorrhage, or death). RESULTS: Over 27 months, there
      were a total of 204 hotline calls regarding 116 patients. Ninety-one percent of
      calls were between 8 a.m. and midnight, and 77% of questions explored issues of
      eligibility for IV tPA, particularly for minor stroke or improving stroke (26%).
      A total of 243 patients were treated with IV tPA at the 12 intervention
      hospitals, 54 of which were following hotline consult. Seventy-six percent of
      hotline patients in whom tPA was recommended actually received tPA, while 2% of
      those in whom tPA was not recommended received the medication. There were no
      differences in protocol deviations (27.8% hotline group vs. 23.8% nonhotline
      group), incidence of symptomatic ICH (5.6% vs. 7.3%), or in-hospital mortality
      (5.6% vs. 13.2%). No medico-legal issues have been reported for any case in the
      study. CONCLUSIONS: Providing tPA decision-making support via telephone consult
      to community physicians is feasible and safe. Consultants may play a more
      prominent role in determining tPA ineligibility than acceptance. Future work
      should include a real-time survey of physician providers to ascertain such
      potential qualitative benefits of a stroke hotline.

PMID- 22978730
TI  - Patient understanding of emergency department discharge instructions: where are
      knowledge deficits greatest?
AB  - OBJECTIVES: Many patients are discharged from the emergency department (ED) with
      an incomplete understanding of the information needed to safely care for
      themselves at home. Patients have demonstrated particular difficulty in
      understanding post-ED care instructions (including medications, home care, and
      follow-up). The objective of this study was to further characterize these
      deficits and identify gaps in knowledge that may place the patient at risk for
      complications or poor outcomes. METHODS: This was a prospective cohort, phone
      interview-based study of 159 adult English-speaking patients within 24 to 36
      hours of ED discharge. Patient knowledge was assessed for five diagnoses (ankle
      sprain, back pain, head injury, kidney stone, and laceration) across the
      following five domains: diagnosis, medications, home care, follow-up, and return
      instructions. Knowledge was determined based on the concordance between direct
      patient recall and diagnosis-specific discharge instructions combined with chart
      review. Two authors scored each case independently and discussed discrepancies
      before providing a final score for each domain (no, minimal, partial, or complete
      comprehension). Descriptive statistics were used for the analyses. RESULTS: The
      study population was 50% female with a median age of 41 years (interquartile
      range [IQR] = 29 to 53 years). Knowledge deficits were demonstrated by the
      majority of patients in the domain of home care instructions (80%) and return
      instructions (79%). Less frequent deficits were found for the domains of follow
      up (39%), medications (22%), and diagnosis (14%). Minimal or no understanding in
      at least one domain was demonstrated by greater than two-thirds of patients and
      was found in 40% of cases for home care and 51% for return instructions. These
      deficits occurred less frequently for domains of follow-up (18%), diagnosis (3%),
      and medications (3%). CONCLUSIONS: Patients demonstrate the most frequent
      knowledge deficits for home care and return instructions, raising significant
      concerns for adherence and outcomes.

PMID- 22978731
TI  - Predicting emergency department inpatient admissions to improve same-day patient
      flow.
AB  - OBJECTIVES: The objectives were to evaluate three models that use information
      gathered during triage to predict, in real time, the number of emergency
      department (ED) patients who subsequently will be admitted to a hospital
      inpatient unit (IU) and to introduce a new methodology for implementing these
      predictions in the hospital setting. METHODS: Three simple methods were compared
      for predicting hospital admission at ED triage: expert opinion, naive Bayes
      conditional probability, and a generalized linear regression model with a logit
      link function (logit-linear). Two months of data were gathered from the Boston VA
      Healthcare System's 13-bed ED, which receives approximately 1,100 patients per
      month. Triage nurses were asked to estimate the likelihood that each of 767
      triaged patients from that 2-month period would be admitted after their ED
      treatment, by placing them into one of six categories ranging from low to high
      likelihood. Logit-linear regression and naive Bayes models also were developed
      using retrospective data and used to estimate admission probabilities for each
      patient who entered the ED within a 2-month time frame, during triage hours
      (1,160 patients). Predictors considered included patient age, primary complaint,
      provider, designation (ED or fast track), arrival mode, and urgency level
      (emergency severity index assigned at triage). RESULTS: Of the three methods
      considered, logit-linear regression performed the best in predicting total bed
      need, with a receiver operating characteristic (ROC) area under the curve (AUC)
      of 0.887, an R(2) of 0.58, an average estimation error of 0.19 beds per day, and
      on average roughly 3.5 hours before peak demand occurred. Significant predictors
      were patient age, primary complaint, bed type designation, and arrival mode (p <
      0.0001 for all factors). The naive Bayesian model had similar positive predictive
      value, with an AUC of 0.841 and an R(2) of 0.58, but with average difference in
      total bed need of approximately 2.08 per day. Triage nurse expert opinion also
      had some predictive capability, with an R(2) of 0.52 and an average difference in
      total bed need of 1.87 per day. CONCLUSIONS: Simple probability models can
      reasonably predict ED-to-IU patient volumes based on basic data gathered at
      triage. This predictive information could be used for improved real-time bed
      management, patient flow, and discharge processes. Both statistical models were
      reasonably accurate, using only a minimal number of readily available independent
      variables.

PMID- 22978732
TI  - Utility of emergency cranial computed tomography in patients without trauma.
AB  - OBJECTIVES: The objectives of this study were to determine, in patients admitted
      to the hospital from the emergency department (ED) without evidence of trauma, 1)
      the prevalence of clinically important abnormalities on cranial computed
      tomography (CCT) and 2) the frequency of emergent therapeutic interventions
      required because of these abnormalities. METHODS: The authors retrospectively
      reviewed the records of all patients from 2007 between the ages of 18 and 89
      years who had CCT as part of their ED evaluations prior to hospitalization.
      Patients with any indication of trauma were excluded, as were those who had a
      lumbar puncture (LP). Chief complaint, results of the ED neurologic examination,
      tomogram findings, and whether patients had emergent interventions were recorded.
      Patients presenting with altered mental status (AMS) were analyzed separately.
      RESULTS: Of the 766 patients meeting inclusion criteria, 83 (11%) had focal
      neurologic findings, and 61 (8%) had clinically important abnormalities on
      computed tomography. Emergent interventions occurred in only 12 (1.6%), 11 (92%)
      of whom had focal neurologic findings. In the subgroup of 287 patients with AMS
      as their presenting problem, 14 (4.9%) had focal findings, six (2%) had
      clinically important abnormalities on tomography, and only two (0.7%) required
      emergent interventions, both of whom had focal findings. Patients presenting with
      AMS were less likely to have positive findings on tomography (odds ratio [OR] =
      0.16, 95% confidence interval [CI] = 0.07 to 0.39). Patients presenting with
      motor weakness or speech abnormalities, or who were unresponsive, were more
      likely to have positive findings on tomography (OR = 4.7, 95% CI = 2.6 to 8.6; OR
      = 4.4, 95% CI = 1.5 to 2.7; and OR = 3.3, 95% CI = 1.6 to 7.1, respectively).
      CONCLUSIONS: Of patients without evidence of trauma who receive CCT in the ED,
      the prevalence of focal neurologic findings and clinically important
      abnormalities on tomography is low, the need for emergent intervention is very
      low, and the large majority of patients requiring emergent intervention have
      focal findings. The yield of CCT was lower for patients presenting with AMS, and
      higher for patients presenting with motor weakness or speech abnormalities, and
      for those who were unresponsive.

PMID- 22978734
TI  - A model for emergency department end-of-life communications after acute
      devastating events--part I: decision-making capacity, surrogates, and advance
      directives.
AB  - Making decisions for a patient affected by sudden devastating illness or injury
      traumatizes a patient's family and loved ones. Even in the absence of an
      emergency, surrogates making end-of-life treatment decisions may experience
      negative emotional effects. Helping surrogates with these end-of-life decisions
      under emergent conditions requires the emergency physician (EP) to be clear,
      making medical recommendations with sensitivity. This model for emergency
      department (ED) end-of-life communications after acute devastating events
      comprises the following steps: 1) determine the patient's decision-making
      capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed
      in completed advance directives; 4) determine patient/surrogate understanding of
      the life-limiting event and expectant treatment goals; 5) convey physician
      understanding of the event, including prognosis, treatment options, and
      recommendation; 6) share decisions regarding withdrawing or withholding of
      resuscitative efforts, using available resources and considering options for
      organ donation; and 7) revise treatment goals as needed. Emergency physicians
      should break bad news compassionately, yet sufficiently, so that surrogate and
      family understand both the gravity of the situation and the lack of long-term
      benefit of continued life-sustaining interventions. EPs should also help the
      surrogate and family understand that palliative care addresses comfort needs of
      the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of
      this communications model reviews determination of decision-making capacity,
      surrogacy laws, and advance directives, including legal definitions and
      application of these steps; Part II (which will appear in a future issue of AEM)
      covers communication moving from resuscitative to end-of-life and palliative
      treatment. EPs should recognize acute devastating illness or injuries, when
      appropriate, as opportunities to initiate end-of-life discussions and to
      implement shared decisions.

PMID- 22978733
TI  - Emergency cricothyroidotomy: a randomized crossover trial comparing percutaneous
      techniques: classic needle first versus "incision first".
AB  - OBJECTIVES: Emergency cricothyroidotomy is potentially lifesaving in patients
      with airway compromise who cannot be intubated or ventilated by conventional
      means. The literature remains divided on the best insertion technique, namely,
      the open/surgical and percutaneous methods. The two are not mutually exclusive,
      and the study hypothesis was that an "incision-first" modification (IF) may
      improve the traditional needle-first (NF) percutaneous approach. This study
      assessed the IF technique compared to the NF method. METHODS: A randomized
      controlled crossover design with concealed allocation was completed for 180
      simulated tracheal models. Attending and resident emergency physicians were
      enrolled. The primary outcome was time to successful cannulation; secondary
      outcomes included needle insertion(s), incision, and dilatation attempts.
      Finally, proportions of intratracheal insertion on the first attempt and
      subjective ease of insertion were compared. RESULTS:   The IF technique was
      significantly faster than the standard NF technique (median = 53 seconds,
      interquartile range [IQR] = 45.0 to 86.4 seconds vs. median = 90 seconds, IQR =
      55.2 to 108.6 seconds; p < 0.001). The median number of needle insertions was
      significantly higher for the NF technique (p = 0.018); there was no significant
      difference in dilation or incision attempts. Intratracheal insertion on the first
      attempt was documented in 90 and 93% of the NF and IF techniques, respectively (p
      = 0.317). All the study participants found the IF hybrid approach easier.
      CONCLUSIONS: The IF modification allows faster access, fewer complications, and
      more favorable clinician endorsement than the classic NF percutaneous technique
      in a validated model of cricothyroidotomy. We suggest therefore that the IF
      technique be considered as an improved method for insertion of an emergency
      cricothyroidotomy.

PMID- 22978735
TI  - The current state of ultrasound training in canadian emergency medicine programs:
      perspectives from program directors.
AB  - OBJECTIVES: There is a paucity of data about emergency ultrasound (EUS) training
      in emergency medicine (EM) residency programs accredited by the Royal College of
      Physicians and Surgeons of Canada (Royal College) and the College of Family
      Physicians of Canada (CFPC). Historically the progress of EUS in Canada has been
      different from that in the United States. We describe the current state of EUS
      training in both Royal College and CFPC-EM programs. METHODS: All Royal College
      EM program directors and all CFPC-EM program directors were invited to
      participate in a website-based survey. Main outcome measures were characteristics
      of currently offered EUS training. RESULTS: The response rate of the survey was
      100% (30/30). EUS is part of the formal residency curriculum in 100% (13/13) of
      Royal College EM programs and in 88% (15/17) of CFPC-EM programs. EM resident
      rotations in ultrasound (US) are provided by 77% (10/13) of Royal College
      programs but only 47% (8/17) of CFPC-EM programs. There are specific requirements
      for numbers of EUS exams to be completed by graduation in 77% (10/13) of Royal
      College programs and 47% (8/17) of CFPC-EM programs. EM faculty and residents
      make clinical decisions and patient dispositions based on their EUS
      interpretation without a consultative study by radiology in 100% (13/13) of Royal
      College programs and 88% (15/17) of CFPC-EM programs. However, 69% (9/13) of
      Royal College programs and 53% (9/17) of CFPC-EM programs have no formal quality
      assurance program in place. CONCLUSIONS: EUS training in Canadian EM programs is
      prevalent, but there are considerable discrepancies among residency programs in
      scope of training, curricula, determination of proficiency, and quality
      assurance. These findings suggest variability in both the level and the quality
      of EUS training in Canada.

PMID- 22978736
TI  - Hand ultrasound: a high-fidelity simulation of lung sliding.
AB  - Simulation training has been effectively used to integrate didactic knowledge and
      technical skills in emergency and critical care medicine. In this article, we
      introduce a novel model of simulating lung ultrasound and the features of lung
      sliding and pneumothorax by performing a hand ultrasound. The simulation model
      involves scanning the palmar aspect of the hand to create normal lung sliding in
      varying modes of scanning and to mimic ultrasound features of pneumothorax,
      including "stratosphere/barcode sign" and "lung point." The simple, reproducible,
      and readily available simulation model we describe demonstrates a high-fidelity
      simulation surrogate that can be used to rapidly illustrate the signs of normal
      and abnormal lung sliding at the bedside.

PMID- 22978737
TI  - High fidelity case-based simulation debriefing: everything you need to know.
AB  - In this 30-minute talk, the authors take an in-depth look at how to debrief high
      fidelity case-based simulation sessions, including discussion on debriefing
      theory, goals, approaches, and structure, as well as ways to create a supportive
      and safe learning environment, resulting in successful small group learning and
      self-reflection. Emphasis is placed on the "debriefing with good judgment"
      approach. Video clips of sample debriefing attempts, highlighting the "dos and
      don'ts" of simulation debriefing, are included. The goal of this talk is to
      provide you with the necessary tools and information to develop a successful and
      effective debriefing approach. There is a bibliography and a quick reference
      guide in Data Supplements S1 and S2 (available as supporting information in the
      online version of this paper).

PMID- 22978738
TI  - Launching Spanish abstracts.

PMID- 22978739
TI  - The evacuation of cairns hospitals due to severe tropical cyclone Yasi.
AB  - On February 2, 2011, Tropical Cyclone Yasi, the largest cyclone to cross the
      Australian coast and a system the size of Hurricane Katrina, threatened the city
      of Cairns. As a result, the Cairns Base Hospital (CBH) and Cairns Private
      Hospital (CPH) were both evacuated, the hospitals were closed, and an alternate
      emergency medical center was established in a sports stadium 15 km from the
      Cairns central business district. This article describes the events around the
      evacuation of 356 patients, staff, and relatives to Brisbane (approximately 1,700
      km away by road), closure of the hospitals, and the provision of a temporary
      emergency medical center for 28 hours during the height of the cyclone. Our
      experience highlights the need for adequate and exercised hospital evacuation
      plans; the need for clear command and control with identified decision-makers;
      early decision-making on when to evacuate; having good communication systems with
      redundancy; ensuring that patients are adequately identified and tracked and have
      their medications and notes; ensuring adequate staff, medications, and oxygen for
      holding patients; and planning in detail the alternate medical facility safety
      and its role, function, and equipment.

PMID- 22978740
TI  - Comparing Methodologies for Evaluating Emergency Medical Services Ground
      Transport Access to Time-critical Emergency Services: A Case Study Using Trauma
      Center Care.
AB  - OBJECTIVES: The regionalization of medical services has resulted in improved
      outcomes and greater compliance with existing guidelines. For certain "time
      critical" conditions intimately associated with emergency medicine, early
      intervention has demonstrated mortality benefits. For these conditions, then,
      appropriate triage within a regionalized system at first diagnosis is paramount,
      ideally occurring in the field by emergency medical services (EMS) personnel.
      Therefore, EMS ground transport access is an important metric in the ongoing
      evaluation of a regionalized care system for time-critical emergency services. To
      our knowledge, no studies have demonstrated how methodologies for calculating EMS
      ground transport access differ in their estimates of access over the same study
      area for the same resource. This study uses two methodologies to calculate EMS
      ground transport access to trauma center care in a single study area to explore
      their manifestations and critically evaluate the differences between the
      methodologies. METHODS: Two methodologies were compared in their estimations of
      EMS ground transport access to trauma center care: a routing methodology (RM) and
      an as-the-crow-flies methodology (ACFM). These methodologies were adaptations of
      the only two methodologies that had been previously used in the literature to
      calculate EMS ground transport access to time-critical emergency services across
      the United States. The RM and ACFM were applied to the nine Level I and Level II
      trauma centers within the province of Ontario by creating trauma center catchment
      areas at 30, 45, 60, and 120 minutes and calculating the population and area
      encompassed by the catchments. Because the methodologies were identical for
      measuring air access, this study looks specifically at EMS ground transport
      access. RESULTS: Catchments for the province were created for each methodology at
      each time interval, and their populations and areas were significantly different
      at all time periods. Specifically, the RM calculated significantly larger
      populations at every time interval while the ACFM calculated larger catchment
      area sizes. This trend is counterintuitive (i.e., larger catchment should mean
      higher populations), and it was found to be most disparate at the shortest time
      intervals (under 60 minutes). Through critical evaluation of the differences, the
      authors elucidated that the ACFM could calculate road access in areas with no
      roads and overestimates access in low-density areas compared to the RM,
      potentially affecting delivery of care decisions. CONCLUSIONS: Based on these
      results, the authors believe that future methodologies for calculating EMS ground
      transport access must incorporate a continuous and valid route through the road
      network as well as use travel speeds appropriate to the road segments traveled;
      alternatively, we feel that variation in methods for calculating road distances
      would have little effect on realized access. Overall, as more complex models for
      calculating EMS ground transport access become used, there needs to be a standard
      methodology to improve and to compare it to. Based on these findings, the authors
      believe that this should be the RM.

PMID- 22978741
TI  - The mortality benefit threshold for patients with suspected pulmonary embolism.
AB  - OBJECTIVES: The mortality benefit for pulmonary embolism (PE) is the difference
      in mortality between treated and untreated patients. The mortality benefit
      threshold is the mortality benefit above which testing for a condition should be
      initiated and below which it should not. To illustrate this concept, the authors
      developed a decision model to estimate the mortality benefit threshold at several
      pretest probabilities for low-risk emergency department (ED) patients with
      possible PE and compare those thresholds with contemporary management of PE in
      the United States and what is known and not known about treatment benefits with
      anticoagulation. METHODS: The authors built a decision model of a 25-year-old
      female with suspected PE. Model inputs were obtained from the literature or
      clinical judgment when data were unavailable. One-way sensitivity analysis was
      used to derive the mortality benefit threshold at several fixed pretest
      probabilities, and two-way sensitivity analysis was used to determine drivers of
      the mortality benefit threshold. RESULTS: At a 15% pretest probability, the
      mortality benefit threshold was 3.7%; at 10% it was 5.2%; at 5% it was 9.8%; at
      2% it was 23.5%; at 1% it was 46.3%; and at 0.5% it was 92.1%. In two-way
      sensitivity analyses, D-dimer specificity, CT angiography (CTA)/CT venography
      (CTV) sensitivity, annual cancer risk, probability of death from renal failure,
      and probability of major bleeding were major model drivers. CONCLUSIONS: The
      mortality benefit threshold for initiating PE testing is very high at low pretest
      probabilities of PE, which should be considered by clinicians in their diagnostic
      approach to PE in the ED. The mortality benefit threshold is a novel way of
      exploring the benefits and risks of ED-based testing, particularly in situations
      like PE where testing (i.e., CT use) carries real risks and the benefits of
      treatment are uncertain.

PMID- 22978742
TI  - Animal models in virus research: their utility and limitations.
AB  - Viral diseases are important threats to public health worldwide. With the number
      of emerging viral diseases increasing the last decades, there is a growing need
      for appropriate animal models for virus studies. The relevance of animal models
      can be limited in terms of mimicking human pathophysiology. In this review, we
      discuss the utility of animal models for studies of influenza A viruses, HIV and
      SARS-CoV in light of viral emergence, assessment of infection and transmission
      risks, and regulatory decision making. We address their relevance and
      limitations. The susceptibility, immune responses, pathogenesis, and
      pharmacokinetics may differ between the various animal models. These complexities
      may thwart translating results from animal experiments to the humans. Within
      these constraints, animal models are very informative for studying virus
      immunopathology and transmission modes and for translation of virus research into
      clinical benefit. Insight in the limitations of the various models may facilitate
      further improvements of the models. 

PMID- 22978743
TI  - Coping with and factors impacting upon the experience of lung cancer in patients
      and primary carers.
AB  - There is a paucity of research exploring patients' and their informal carers'
      experience of coping with and factors impacting on the lung cancer experience.
      This study aims to explore how patients and their informal carers cope with a
      diagnosis of lung cancer and describe the key factors that mediate distress in
      this population in order that they may be better supported in the future. This
      was a qualitative study employing semi-structured interviews and framework
      analysis to elicit the experience of 37 patients with lung cancer and 23 primary
      carers regarding their coping with and factors influencing patient/carer
      distress. The findings illustrate that participants used both emotional- and
      problem-focused coping strategies, including accepting the reality of lung
      cancer, adopting a positive attitude/fighting spirit, denial, avoidance and
      distraction and information seeking. Maintaining normality was also important.
      Key factors that mediate the lung cancer experience were also identified
      including hope, social network, prior experience of cancer and other chronic
      illnesses, the competing coping strategies of patients and their primary carers,
      the unpredictable nature of patients' behaviour, changing symptomatology, the
      perceived attitudes of health professionals and the impact of perceived delays in
      diagnosis. This study provides important insights into how patients with lung
      cancer and their primary carers might be better supported.

PMID- 22978744
TI  - Effect of deferiprone, an oral iron chelator, in diabetic and non-diabetic
      glomerular disease.
AB  - Compelling experimental evidence exists for the role of oxidants and iron in
      glomerular disease. In preliminary studies, we confirmed increased urinary
      catalytic iron in patients with glomerulonephritis and diabetic nephropathy. We
      conducted two separate single-center, prospective, single-armed, open-labeled,
      proof-of-concept studies to evaluate the safety and efficacy of an oral iron
      chelator in patients with glomerulonephritis and diabetic nephropathy. Study 1
      comprised 15 patients with biopsy-proven glomerulonephritis who had persistent
      proteinuria despite treatment with steroids and/or cyclophosphamides. Study 2
      comprised 38 adult patients with diabetic nephropathy. Patients in Study 1 were
      treated with deferiprone (50 mg/kg/day) in three divided doses for 6 months and
      Study 2 patients were treated for 9 months. In Study 1, two patients had severe
      gastrointestinal intolerance and withdrew from the study after one dose and are
      not included in the results. There was a significant reduction (47 +/- 9% mean)
      in 24-h urinary protein (4.01 +/- 1.61 to 2.21 +/- 1.62 [p = 0.009]), with no
      significant changes in serum creatinine. In Study 2, treatment with deferiprone
      resulted in a marked, persistent drop in the mean albumin/creatinine ratio (187
      +/- 47 at baseline to 25 +/- 7 mg/g, [p = 0.01]) and stable renal function over a
      9-month period. No clinically significant adverse events were observed in either
      study. Although these are small, open-labeled, and non-randomized studies, our
      results suggest that future randomized, double-blind trials examining the utility
      of deferiprone to treat glomerular diseases appear warranted.

PMID- 22978745
TI  - Anti-AIDS agents 90. novel C-28 modified bevirimat analogues as potent HIV
      maturation inhibitors.
AB  - In a continuing study of bevirimat (2), the anti-HIV-maturation clinical trials
      agent, 28 new betulinic acid (BA, 1) derivatives were designed and synthesized.
      Among these compounds, 17, with a C-28 MEM ester moiety, and 22, with a C-28
      ethyl hexanoate, increased the anti-HIV replication activity compared with 2 by 2
      fold while compounds 40, 41, 48, and 49, with C-28 piperazine or piperidine amide
      substitutions, increased the activity by 3- to 15-fold. The best new compound,
      41, exhibited an anti-HIV IC(50) of 0.0059 MUM compared with 0.087 MUM for 2. All
      of the active compounds showed only antimaturation effects, as confirmed by TZM
      bl assay, in blocking the HIV replication. The results suggest that proper C-28
      substitutions can further enhance the antimaturation activity of 2 without any
      antientry effects. Thus, 41 may serve as a promising new lead for development of
      anti-AIDS clinical trial candidates.

PMID- 22978746
TI  - Scleral changes induced by atropine in chicks as an experimental model of myopia.
AB  - PURPOSE: To determine the effects of intravitreal atropine on scleral growth in
      the form-deprived chick as an experimental model of myopia. METHODS: Five groups
      of five chicks were studied from day 0-12 post-hatching. One group remained
      untreated (C), and four were form-deprived by monocular light diffusers to induce
      myopia. Two groups (RL and A) wore diffusers for 9 days, and the other two groups
      (D and D + A) wore diffusers throughout the study. Group D received no further
      treatment (myopia positive control). Groups A and D + A received intravitreal
      injections of atropine for days 9-12. Measurements of refractive error and axial
      length were performed on days 0, 9, and 12. Sclera changes were assessed in
      cartilaginous and fibrous layers by histological analysis. RESULTS: All form
      deprived eyes had a myopic refractive error on day 9. All atropine-treated groups
      were hyperopic on day 12. The effect of atropine was most evident in Group D + A
      in which diffusers were maintained throughout treatment and changes in refractive
      error were statistically significant. The observed changes in axial length were
      in line with the changes in refractive error. The scleral fibrous layer thickness
      increased, and the sceral cartilaginous layer underwent a slight thinning
      compared to Group D, the myopia positive control. CONCLUSIONS: If the signals
      that induce growth remain during atropine treatment, morphological changes in
      sclera are produced: the scleral fibrous layer thickened, and the sceral
      cartilaginous layer thinned. These changes resulted in refractive error recovery,
      and the ocular growth was stopped. The data suggested the atropine was acting
      throughout the scleral fibrous layer.

PMID- 22978747
TI  - Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Pre-gestational diabetes mellitus is associated with increased risk
      for maternal and fetal adverse outcomes. This systematic review was carried out
      to evaluate the effectiveness and safety of pre-pregnancy care in improving the
      rate of congenital malformations and perinatal mortality for women with pre
      gestational diabetes mellitus. METHODS: We searched the following databases,
      MEDLINE, EMBASE, WEB OF SCIENCE, Cochrane Library, including the CENTRAL register
      of controlled trials and CINHAL up to December 2011, without language
      restriction, for any pre-pregnancy care aiming at health promotion, glycemic
      control and screening and treatment of diabetes complications in women with type
      I or type II diabetes mellitus. Study design were trials (randomized and non
      randomized), cohort and case-control studies. RESULTS: Of the 2452 title scanned
      54 full papers were retrieved of those 21 studies were included in this review.
      Twelve cohort studies at low and medium risk of bias, with 3088 women, were
      included in the meta-analysis. Meta-analysis suggested that pre-pregnancy care is
      effective in reducing congenital malformation, Risk Ratio (RR) 0.25 (95% CI 0.16
      0.37), number needed to treat (NNT) 19 (95% CI 14-24), and perinatal mortality RR
      0.34 (95% CI 0.15-0.75), NNT = 46 (95% CI 28-115). Pre-pregnancy care lowers
      glycosylated hemoglobin A1c (HbA1c) in the first trimester of pregnancy by an
      average of 1.92% (95% CI -2.05 to -1.79). However women who received pre
      pregnancy care were at increased risk of hypoglycemia during the first trimester
      of pregnancy RR 1.51 (95% CI 1.15-1.99). CONCLUSION: Pre-pregnancy care for women
      with pre-gestational type 1 or type 2 diabetes mellitus is effective in improving
      rates of congenital malformations, perinatal mortality and in reducing maternal
      HbA1C in the first trimester of pregnancy. Pre-pregnancy care might cause
      maternal hypoglycemia in the first trimester of pregnancy.

PMID- 22978748
TI  - Vortioxetine (Lu AA21004) in the long-term open-label treatment of major
      depressive disorder.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the safety and
      tolerability of the investigational drug vortioxetine (Lu AA21004) in the long
      term treatment of patients with major depressive disorder. METHODS: Patients
      entered this 52-week, open-label extension study after completing an 8-week lead
      in study. Safety and tolerability were evaluated at regular intervals on the
      basis of spontaneously reported adverse events (AEs), clinical safety laboratory
      tests, vital signs, ECG and physical examination. Effectiveness of treatment was
      assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) total score.
      RESULTS: A total of 535 patients were treated and 61.3% (n = 328) completed the
      study, resulting in 393 patient years of exposure to vortioxetine. AEs reported
      by >=10% of patients were nausea, headache, and nasopharyngitis. Taken together,
      six patients had eight AEs related to sexual dysfunction. There were no
      clinically significant safety findings with respect to mean changes of vital
      signs, weight, ECG parameters, or clinical laboratory values. Patients entered
      the extension study with a mean MADRS total score of 13.5 +/- 8.7. The mean MADRS
      total score decreased (improved) by approximately 8 points to 5.5 +/- 6.0 at Week
      52 (OC). By the end of the study, the proportion of responders had increased from
      63% to 94% (OC), as had the proportion in remission (MADRS <=10), increasing from
      42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a
      relapse rate (MADRS >=22) of 9.7%. CONCLUSIONS: As with all open-label studies,
      the conclusions that can be drawn are limited by the lack of a placebo control,
      making it difficult to assess causality of any changes in outcome measures.
      However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day)
      demonstrated a favourable safety and tolerability profile and maintained
      effectiveness over 12 months of treatment. TRIAL REGISTRATION: This study has the
      ClinicalTrials.gov identifier: NCT00694304.

PMID- 22978750
TI  - Theoretical investigation on the steric interaction in colloidal deposition.
AB  - A theoretical investigation was conducted upon the steric interaction between a
      spherical particle and a flat plate. The effects of curvature on both the segment
      density distribution of polymer and on the steric interaction energy between a
      particle and a plate were examined. It was found that the conventional approach
      using Derjaguin approximation may overestimate the interaction energy, especially
      for very small particles. Based on the results obtained from applying the Flory
      Krigbaum theory with the accurate geometry change during the interaction, simple
      approximate expressions of exponential form were proposed for both the osmotic
      (mixing) and elastic contributions to the steric interaction energy for a sphere
      plate interaction. The proposed model was validated against a set of experimental
      results from a reported study employing atomic force microscopy. Also
      investigated was the steric interaction between a spherical particle coated with
      polymer and an uncoated flat surface. It was found that the steric interaction
      energy from the osmotic contribution is significantly higher than that from the
      elastic contribution and that steric interaction is considerably weaker when the
      polymer exists on only one of the interacting surfaces.

PMID- 22978749
TI  - The HUNT study: participation is associated with survival and depends on
      socioeconomic status, diseases and symptoms.
AB  - BACKGROUND: Population based studies are important for prevalence, incidence and
      association studies, but their external validity might be threatened by
      decreasing participation rates. The 50 807 participants in the third survey of
      the HUNT Study (HUNT3, 2006-08), represented 54% of the invited, necessitating a
      nonparticipation study. METHODS: Questionnaire data from HUNT3 were compared with
      data collected from several sources: a short questionnaire to nonparticipants,
      anonymous data on specific diagnoses and prescribed medication extracted from
      randomly selected general practices, registry data from Statistics Norway on
      socioeconomic factors and mortality, and from the Norwegian Prescription Database
      on drug consumption. RESULTS: Participation rates for HUNT3 depended on age, sex
      and type of symptoms and diseases, but only small changes were found in the
      overall prevalence estimates when including data from 6922 nonparticipants. Among
      nonparticipants, the prevalences of cardiovascular diseases, diabetes mellitus
      and psychiatric disorders were higher both in nonparticipant data and data
      extracted from general practice, compared to that reported by participants,
      whilst the opposite pattern was found, at least among persons younger than 80
      years, for urine incontinence, musculoskeletal pain and headache. Registry data
      showed that the nonparticipants had lower socioeconomic status and a higher
      mortality than participants. CONCLUSION: Nonparticipants had lower socioeconomic
      status, higher mortality and showed higher prevalences of several chronic
      diseases, whilst opposite patterns were found for common problems like
      musculoskeletal pain, urine incontinence and headache. The impact on associations
      should be analyzed for each diagnosis, and data making such analyses possible are
      provided in the present paper.

PMID- 22978751
TI  - Molecular mechanism of direct proflavine-DNA intercalation: evidence for drug
      induced minimum base-stacking penalty pathway.
AB  - DNA intercalation, a biophysical process of enormous clinical significance, has
      surprisingly eluded molecular understanding for several decades. With appropriate
      configurational restraint (to prevent dissociation) in all-atom metadynamics
      simulations, we capture the free energy surface of direct intercalation from
      minor groove-bound state for the first time using an anticancer agent proflavine.
      Mechanism along the minimum free energy path reveals that intercalation happens
      through a minimum base stacking penalty pathway where nonstacking parameters
      (Twist->Slide/Shift) change first, followed by base stacking parameters
      (Buckle/Roll->Rise). This mechanism defies the natural fluctuation hypothesis and
      provides molecular evidence for the drug-induced cavity formation hypothesis. The
      thermodynamic origin of the barrier is found to be a combination of entropy and
      desolvation energy.

PMID- 22978752
TI  - Probing the mycobacterial trehalome with bioorthogonal chemistry.
AB  - Mycobacteria, including the pathogen Mycobacterium tuberculosis, use the non
      mammalian disaccharide trehalose as a precursor for essential cell-wall
      glycolipids and other metabolites. Here we describe a strategy for exploiting
      trehalose metabolic pathways to label glycolipids in mycobacteria with azide
      modified trehalose (TreAz) analogues. Subsequent bioorthogonal ligation with
      alkyne-functionalized probes enabled detection and visualization of cell-surface
      glycolipids. Characterization of the metabolic fates of four TreAz analogues
      revealed unique labeling routes that can be harnessed for pathway-targeted
      investigation of the mycobacterial trehalome.

PMID- 22978753
TI  - Speech based optimization of cochlear implants.
AB  - OBJECTIVE: This study describes an innovative method to optimize cochlear implant
      (CI) devices for individual patients using speech stimuli. DESIGN: Baseline
      performance of clinically created CI settings was evaluated objectively (CNC and
      BKB-SIN) and subjectively (listening situation questionnaire). Participants
      underwent the Clarujust optimization procedure during two sessions, each two
      weeks apart, allowing for acclimatization and experience with each group of
      programs. Outcome testing was completed on both optimization settings during the
      two week follow-up session. CNC and BKB-SIN scores were compared within
      participants across test sessions. STUDY SAMPLE: Twenty adult experienced CI
      users were reprogrammed using the ClarujustTM fitting procedure. RESULTS:
      Significant improvements (p < 0.05) on CNC words and BKB-SIN sentences were
      observed with optimized maps compared to maps programmed using standard methods.
      Subjective performance also showed increased satisfaction with the optimized
      maps. The maps for individual users varied significantly and no single fitting
      applied for all patients. CONCLUSIONS: The Clarujust optimization method of
      programming CIs shows promise to improve patient performance and increase patient
      satisfaction in a shorter clinical test time.

PMID- 22978754
TI  - Strategy for minimizing between-study variation of large-scale phenotypic
      experiments using multivariate analysis.
AB  - We have developed a multistep strategy that integrates data from several large
      scale experiments that suffer from systematic between-experiment variation. This
      strategy removes such variation that would otherwise mask differences of
      interest. It was applied to the evaluation of wood chemical analysis of 736
      hybrid aspen trees: wild-type controls and transgenic trees potentially involved
      in wood formation. The trees were grown in four different greenhouse experiments
      imposing significant variation between experiments. Pyrolysis coupled to gas
      chromatography/mass spectrometry (Py-GC/MS) was used as a high throughput
      screening platform for fingerprinting of wood chemotype. Our proposed strategy
      includes quality control, outlier detection, gene specific classification, and
      consensus analysis. The orthogonal projections to latent structures discriminant
      analysis (OPLS-DA) method was used to generate the consensus chemotype profiles
      for each transgenic line. These were thereafter compiled to generate a global
      dataset. Multivariate analysis and cluster analysis techniques revealed a drastic
      reduction in between-experiment variation that enabled a global analysis of all
      transgenic lines from the four independent experiments. Information from in-depth
      analysis of specific transgenic lines and independent peak identification
      validated our proposed strategy.

PMID- 22978755
TI  - The neurophysiological performance of visuospatial working memory in children
      with developmental coordination disorder.
AB  - AIM: The objective of this study was to investigate the mechanisms underlying the
      deficit in visuospatial working memory (VSWM) seen in children with developmental
      coordination disorder (DCD) and to compare brain activity while performing a VSWM
      task in children with DCD and typically developing children. METHOD: Behavioural
      performance and event-related potentials (ERPs) were recorded in 24 children (12
      males, 12 females; mean age 139 mo, SD 4 mo) with DCD (as determined by a score
      <5th centile on the Movement Assessment Battery for Children - Second Edition)
      and in 30 age- and sex-matched typically developing children (15 males; 15
      females; mean age 140 mo, SD 5 mo) recruited from local schools, while performing
      one spatial non-delay and two time-delayed spatial memory tasks. RESULTS:
      Compared with typically developing children, children with DCD exhibited longer
      reaction times (p = 0.022; partial eta(2) =0.10) and lower accuracy rates (p <
      0.001; partial eta(2) = 0.35) on the two spatial memory tasks.
      Electrophysiological indices also showed distinct modulatory effects, with
      children with DCD exhibiting smaller P3 (p < 0.001; partial eta(2) = 0.26) and
      positive slow wave (pSW; p = 0.003; partial eta(2) = 0.16) amplitude and a
      smaller area under the curve of P3 and pSW components (p = 0.002; partial eta(2)
      = 0.17). INTERPRETATION: The combined analysis of behavioural performance and ERP
      data suggests that children with DCD have deficits of visuospatial working memory
      owing to fewer resources being allocated to comparison of spatial locations, less
      effort allotted to the response selection, and less neural processing employed
      during the retrieval process phase.

PMID- 22978756
TI  - Developmental synchronization of male and female gametophytes in Ginkgo biloba
      and its neck mother cell division prior to fertilization.
AB  - This study investigated male and female gametophytes in Ginkgo biloba, while a
      droplet of fluid was present in the fertilization chamber and found that the
      central cell, the generative cell and the neck mother cell divided simultaneously
      prior to fertilization. In male gametophytes, the generative cell divided to
      yield two sperm cells. Concomitantly, the two neck mother cells of the
      archegonium increased in size then divided asymmetrically resulting in two big
      cover cells and two small base cells. Each cell had a fixed end in direct contact
      with an adjacent jacket cell and a free end overlapping its counterpart. This
      unique arrangement could allow for their free ends to swing into the
      fertilization chamber as a result of the force from the interior of the
      archegonium where a polar periclinal division had occurred to produce a canal
      cell and an egg. The subsequent withdrawal of the content of the archegonium may
      facilitate the entry of sperm into the archegonium. The neck apparatus closed
      after the fertilization occurred. The concurrence of the above divisions and the
      delicate structure of neck apparatus suggest that the gametophytes undergo a
      synchronization process to become receptive at the time of fertilization.
      However, the formation of neck cells and the opening time of neck apparatus of
      the archegonia within the same ovule were slightly different, which could lead to
      the formation of zygotes at a temporally distinct interval. The earlier formed
      zygote may progress as the only mature embryo in the ovule.

PMID- 22978757
TI  - Cellular sources of dysregulated cytokines in relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND: Numerous cytokines are implicated in the immunopathogenesis of
      multiple sclerosis (MS), but studies are often limited to whole blood (WB) or
      peripheral blood mononuclear cells (PBMCs), thereby omitting important
      information about the cellular origin of the cytokines. Knowledge about the
      relation between blood and cerebrospinal fluid (CSF) cell expression of cytokines
      and the cellular source of CSF cytokines is even more scarce. METHODS: We studied
      gene expression of a broad panel of cytokines in WB from relapsing-remitting
      multiple sclerosis (RRMS) patients in remission and healthy controls (HCs).
      Subsequently we determined the gene expression of the dysregulated cytokines in
      isolated PBMC subsets (CD4+, CD8+T-cells, NK-cells, B-cells, monocytes and
      dendritic cells) from RRMS patients and HCs and in CSF-cells from RRMS patients
      in clinical relapse and non-inflammatory neurological controls (NIND). RESULTS:
      RRMS patients had increased expression of IFN-gamma (IFNG), interleukin (IL) 1
      beta (IL1B), IL7, IL10, IL12A, IL15, IL23, IL27, lymphotoxin-alpha (LTA) and
      lymphotoxin-beta (LTB) in WB. In PBMC subsets the main sources of pro
      inflammatory cytokines were T- and B-cells, whereas monocytes were the most
      prominent source of immunoregulatory cytokines. In CSF-cells, RRMS patients had
      increased expression of IFNG and CD19 and decreased expression of IL10 and CD14
      compared to NINDs. CD19 expression correlated with expression of IFNG, IL7,
      IL12A, IL15 and LTA whereas CD14 expression correlated with IL10 expression.
      CONCLUSIONS: Using a systematic approach, we show that expression of pro
      inflammatory cytokines in peripheral blood primarily originates from T- and B
      cells, with an important exception of IFNG which is most strongly expressed by NK
      cells. In CSF-cell studies, B-cells appear to be enriched in RRMS and associated
      with expression of pro-inflammatory cytokines; contrarily, monocytes are
      relatively scarce in CSF from RRMS patients and are associated with IL10
      expression. Thus, our findings suggest a pathogenetic role of B-cells and an
      immunoregulatory role of monocytes in RRMS.

PMID- 22978758
TI  - Determination of LCt(50)s in anesthetized rats exposed to aerosolized nerve
      agents.
AB  - Nerve agents pose a threat to the respiratory tract with exposure that could
      result in acute compromised lung performance and death. The determination of
      toxicity by inhalation is important for the rational development of timely
      therapeutic countermeasures. This study was designed to deliver aerosolized
      dilute nerve agents in a dose-response manner to investigate the extent of
      lethality of nerve agents: soman, sarin, VX and VR. Male rats (240-270 g) were
      anesthetized intramuscularly with 10 mg/kg xylazine and 90 mg/kg ketamine.
      Following anesthesia, rats were intubated with a glass endotracheal tube (ET) and
      placed in a glove box. The ET was connected to a closed circuit nebulizer system
      (Aeroneb, Aerogen, Inc.) that delivered a particle size of < 2.0 um and was in
      series between the ventilator and the ET. Nerve agents were delivered by a small
      animal ventilator set for a volume of 2.5 mL * 60-80 breaths/min. VX or VR were
      nebulized and delivered in concentrations ranging from 6.25-800 ug/kg over a 10
      min exposure time period. Sarin (GB) or soman (GD), 6.5-1250 ug/kg, were
      delivered in a similar manner. Lethality by inhalation occurred either during the
      10-min exposure period or less than 15 min after the cessation of exposure.
      Survivors were euthanized at 24 h postexposure. LCt(50) estimates (+/- 95%
      confidence intervals [CIs]) were obtained from the sequential stage-wise
      experiments using the probit analysis. Probit analysis revealed that the LD(50)
      for VX was 110.7 ug/kg (CI: 73.5-166.7), VR 64.2 ug/kg (CI: 42.1-97.8); soman
      (GD), 167 ug/kg (CI: 90-310), and sarin (GB), 154 ug/kg (CI: 98-242),
      respectively. Although VR is a structural isomer of VX, the compounds appear to
      be markedly different in terms of toxicity when delivered by aerosol. These
      relationships were converted to actual 10 min LCt(50) equivalents: VX = 632.2, VR
      = 367, GD = 954.3 and GB = 880 mg.min/m(3). Validation of exposure was verified
      by the determination of blood levels of acetylcholinesterase (AChE) across doses
      for the agent VR.

PMID- 22978759
TI  - CXCR7 mediates SDF1-induced melanocyte migration.
AB  - Melanoblasts are derived from the neural crest and migrate to the
      dermal/epidermal border of skin and hair bulges. Although melanoblast migration
      during embryogenesis has been well investigated, there are only a few reports
      regarding the migration of mature melanocytes. Here, we demonstrate that a
      chemokine, stromal-derived factor-1 (SDF1, also known as CXCL12), and one of its
      receptor CXCR7 regulate normal human epidermal melanocyte (NHEM) migration. We
      found that SDF1 induces the directional migration of NHEMs. Interestingly,
      although both CXCR4 and CXCR7 are expressed in NHEMs, blockade of CXCR4 using a
      CXCR4-specific neutralizing antibody did not exert any influence on the SDF1
      induced migration of NHEMs, whereas blockade of CXCR7 using a CXCR7-specific
      neutralizing antibody did influence migration. Furthermore, SDF1-induced NHEMs
      migration exhibited the early hallmark events of CXCR7 signaling associated with
      MAP kinase activation. It is known that the phosphorylation of ERK through CXCR7
      signaling is mediated by beta-arrestins. The treatment of NHEMs with SDF1
      resulted in the phosphorylation of ERK in a beta-arrestin 2-dependent manner.
      These results suggest that melanocytes may have a unique mechanism of migration
      via SDF1/CXCR7 signaling that is different from that of other cell types.

PMID- 22978760
TI  - Mechanoanions produced by mechanical fracture of bacterial cellulose: ionic
      nature of glycosidic linkage and electrostatic charging.
AB  - Mechanoanions were produced by heterogeneous scission of the glycosidic linkages
      of the main chain of bacterial cellulose (BC); scission was induced by mechanical
      fracture of the BC in a vacuum in the dark at 77 K. The mechanoanions were
      detected using electron-spin-trapping methods with tetracyanoethylene. The yield
      of mechanoanions was positively correlated with the absolute value of the change
      in the Mulliken atomic charge, which was used as a descriptor of the ionic nature
      of the glycosidic linkage. Homogeneous scission of the glycosidic linkages
      induced by mechanical fracture generated mechanoradicals, the electron affinity
      of which was estimated on the basis of the energy of the lowest unoccupied
      molecular orbital for the model structure of the mechanoradical. It was concluded
      that the electrostatic charging of BC is caused by electron transfer from
      mechanoanions to mechanoradicals, which have high electron affinities. The
      electrostatic charge density of BC in a vacuum in the dark at 77 K was estimated
      to be 6.00 * 10(-1) C/g.

PMID- 22978761
TI  - Activity, distribution and function of indole-3-acetic acid biosynthetic pathways
      in bacteria.
AB  - The capacity to produce the phytohormone indole-3-acetic acid (IAA) is widespread
      among bacteria that inhabit diverse environments such as soils, fresh and marine
      waters, and plant and animal hosts. Three major pathways for bacterial IAA
      synthesis have been characterized that remove the amino and carboxyl groups from
      the alpha-carbon of tryptophan via the intermediates indolepyruvate,
      indoleacetamide, or indoleacetonitrile; the oxidized end product IAA is typically
      secreted. The enzymes in these pathways often catabolize a broad range of
      substrates including aromatic amino acids and in some cases the branched chain
      amino acids. Moreover, expression of some of the genes encoding key IAA
      biosynthetic enzymes is induced by all three aromatic amino acids. The broad
      distribution and substrate specificity of the enzymes suggests a role for these
      pathways beyond plant-microbe interactions in which bacterial IAA has been best
      studied. 

PMID- 22978762
TI  - Helicity control of an indolocarbazole foldamer by chiral organic anions.
AB  - Chiral organic anions such as camphorsulfonates and cAMP give rise to the
      preferential formation of a one-handed helix of an indolocarbazole foldamer, thus
      inducing characteristic circular dichroic (CD) signals. Moreover, the on and off
      switching of the chiroptical signal can be operated by acid and base chemistry
      which efficiently controls the association and dissipation of the foldamer and
      cAMP.

PMID- 22978763
TI  - Exclusive image guided IMRT vs. radical prostatectomy followed by postoperative
      IMRT for localized prostate cancer: a matched-pair analysis based on risk-groups.
AB  - BACKGROUND: To investigate whether patients treated for a localized prostate
      cancer (PCa) require a radical prostatectomy followed by postoperative
      radiotherapy or exclusive radiotherapy, in the modern era of image guided IMRT.
      METHODS: 178 patients with PCa were referred for daily exclusive image guided
      IMRT (IG-IMRT) using an on-line 3D ultra-sound based system and 69 patients were
      referred for postoperative IMRT without image guidance after radical
      prostatectomy (RP + IMRT). Patients were matched in a 1:1 ratio according to
      their baseline risk group before any treatment. Late toxicity was scored using
      the CTV v3.0 scale. Biochemical failure was defined as a postoperative PSA <= 0.1
      ng/mL followed by 1 consecutive rising PSA for the postoperative group of
      patients and by the Phoenix definition (nadir + 2 ng/mL) for the group of
      patients treated with exclusive radiotherapy. RESULTS: A total of 98 patients
      were matched (49:49). From the start of any treatment, the median follow-up was
      56.6 months (CI 95% = [49.6-61.2], range [18.2-115.1]). No patient had late
      gastrointestinal grade >= 2 toxicity in the IG-IMRT group vs. 4% in the RP + IMRT
      group. Forty two percent of the patients in both groups had late grade >= 2
      genitourinary toxicity. The 5-year FFF rates in the IG-IMRT group and in the RP +
      IMRT groups were 93.1% [80.0-97.8] and 76.5% [58.3-87.5], respectively (p =
      0.031). CONCLUSIONS: Patients with a localized PCa treated with IG-IMRT had
      better oncological outcome than patients treated with RP + IMRT. Further
      improvements in postoperative IMRT using image guidance and dose escalation are
      urgently needed.

PMID- 22978764
TI  - Relationships among genera of the Saccharomycotina (Ascomycota) from multigene
      phylogenetic analysis of type species.
AB  - Relationships among ascomycetous yeast genera (subphylum Saccharomycotina, phylum
      Ascomycota) have been uncertain. In the present study, type species of 70
      currently recognized genera are compared from divergence in the nearly entire
      nuclear gene sequences for large subunit rRNA, small subunit (SSU) rRNA,
      translation elongation factor-1alpha, and RNA polymerase II, subunits 1 (RPB1)
      and 2 (RPB2). The analysis substantiates earlier proposals that all known
      ascomycetous yeast genera now assigned to the Saccharomycotina represent a single
      clade. Maximum likelihood analysis resolved the taxa into eight large multigenus
      clades and four-one- and two-genus clades. Maximum parsimony and neighbor-joining
      analyses gave similar results. Genera of the family Saccharomycetaceae remain as
      one large clade as previously demonstrated, to which the genus Cyniclomyces is
      now assigned. Pichia, Saturnispora, Kregervanrija, Dekkera, Ogataea and
      Ambrosiozyma are members of a single large clade, which is separate from the
      clade that includes Barnettozyma, Cyberlindnera, Phaffomyces, Starmera and
      Wickerhamomyces. Other clades include Kodamaea, Metschnikowia, Debaryomyces,
      Cephaloascus and related genera, which are separate from the clade that includes
      Zygoascus, Trichomonascus, Yarrowia and others. This study once again
      demonstrates that there is limited congruence between a system of classification
      based on phenotype and a system determined from DNA sequences.

PMID- 22978765
TI  - Neonatal aortic dilatation associated with vitamin A deficiency and its
      subsequent remission after supplementation therapy.

PMID- 22978766
TI  - The missing nipple: a rare case of Basal cell carcinoma of the nipple in a
      Chinese female.

PMID- 22978767
TI  - Disparities in aspects of oral-health-related quality of life among Chilean
      adults.
AB  - OBJECTIVE: Socioeconomic disparities in oral health among adults have been
      observed in many countries, but it is not clear whether they exist in aspects of
      Oral Health-Related Quality of Life in Chile. METHODS: Data were analyzed from
      the 1st National Health Survey (NHIS) of Chilean adults, conducted in 2003. It
      included questions on aspects of oral-health-related quality of life (OHRQoL),
      including problems ('always' or 'almost always') with speaking, eating, pain, or
      daily activities. These were the dependent variables. Covariates included age,
      sex, education level, rurality, smoking, general quality of life, the number of
      remaining teeth, the number of untreated decayed teeth, and the reason for the
      last dental visit. Multivariate modelling was used to describe disparities in
      aspects of OHRQoL, using education level as the marker for socioeconomic status.
      RESULTS: The sample comprised 3050 participants (54.7% female), of whom 49.0%,
      40.5% and 10.5% had been educated to primary, secondary or tertiary level
      respectively. In the bivariate analysis, there were significant gradients in all
      four aspects of OHRQoL across those three categories. Covariates significantly
      associated with poorer OHRQoL were female gender, rurality, and poor self
      reported general quality of life, and these were subsequently controlled for in
      the multivariate analysis. Adults with primary education (or less) were more
      likely than their tertiary-educated counterparts to report problems speaking
      (relative risk = 2.38; CI: 1.41, 4.05), trouble or pain (relative risk = 2.77;
      CI: 1.56, 4.91), discomfort in eating with others (relative risk = 2.35; CI:
      1.34, 4.10), and interference with activities of daily living (relative risk =
      2.29; CI: 1.15, 4.55). Those educated only to secondary level had relative risks
      which were lower than these but still significantly different from the reference
      category. The number of teeth with untreated caries was positively associated
      with impaired OHRQoL, and the number of remaining teeth was negatively associated
      with it. CONCLUSIONS: Socio-economic disparities in oral-health-related quality
      of life are apparent among Chilean adults, and remain after adjusting for dental
      status.

PMID- 22978768
TI  - The relationship between physical activity and heart rate variability in
      orthotopic heart transplant recipients.
AB  - AIMS AND OBJECTIVES: To investigate the relationship between physical activity
      and heart rate variability in orthotopic heart transplant recipients, to compare
      the difference in heart rate variability between patients one year after
      orthotopic heart transplant and healthy adults matched to the heart transplant
      recipients in terms of age, gender and physical activity levels. BACKGROUND:
      Although physical activity affects the heart rate variability in patients with
      heart disease, there is a paucity of literature discussing the correlation
      between physical activity and heart rate variability among heart transplant
      recipients. DESIGN: This was a descriptive and cross-sectional study. METHODS: A
      total of 120 eligible subjects were divided into the orthotopic heart transplant
      recipient group (n = 60) and the healthy adult group (n = 60). The Seven-day
      Physical Activity Recall questionnaire was used to record the subjects' amount of
      physical activity per week. Heart rate variety parameters were determined by
      separate frequency domain components. RESULTS: Results indicated heart transplant
      recipients' heart rate variety was significantly lower than that of healthy
      adults in terms of mean, sdr, total power (ms(2)), low frequency (ms(2)), low
      frequency (nu), high frequency (ms(2)) and low frequency/high frequency. Heart
      transplant recipients' heart rate variety including total power (ms(2)), low
      frequency (ms(2)) and high frequency (ms(2)) was 18.2, 2 and 7.2% of healthy
      controls, respectively; the amount of absolutely and relatively moderate physical
      activity was positively related to high frequency (ms(2)) and high frequency
      (nu), but was negatively related to low frequency/high frequency. High frequency
      (nu) increases while the total amount of weekly physical activity increases.
      CONCLUSIONS: Results confirmed that the more the moderate physical activity
      performed, the better the patient's heart rate variability. RELEVANCE TO CLINICAL
      PRACTICE: We suggest that clinical care providers have to encourage heart
      transplant recipients to engage in moderate physical activity.

PMID- 22978769
TI  - Specificity and multiplicity in the recognition of individuals: implications for
      the evolution of social behaviour.
AB  - Recognition of conspecifics occurs when individuals classify sets of conspecifics
      based on sensory input from them and associate these sets with different
      responses. Classification of conspecifics can vary in specificity (the number of
      individuals included in a set) and multiplicity (the number of sets
      differentiated). In other words, the information transmitted varies in
      complexity. Although recognition of conspecifics has been reported in a wide
      variety of organisms, few reports have addressed the specificity or multiplicity
      of this capability. This review discusses examples of these patterns, the
      mechanisms that can produce them, and the evolution of these mechanisms.
      Individual recognition is one end of a spectrum of specificity, and binary
      classification of conspecifics is one end of a spectrum of multiplicity. In some
      cases, recognition requires no more than simple forms of learning, such as
      habituation, yet results in individually specific recognition. In other cases,
      recognition of individuals involves complex associations of multiple cues with
      multiple previous experiences in particular contexts. Complex mechanisms for
      recognition are expected to evolve only when simpler mechanisms do not provide
      sufficient specificity and multiplicity to obtain the available advantages. In
      particular, the evolution of cooperation and deception is always promoted by
      specificity and multiplicity in recognition. Nevertheless, there is only one
      demonstration that recognition of specific individuals contributes to cooperation
      in animals other than primates. Human capacities for individual recognition
      probably have a central role in the evolution of complex forms of human
      cooperation and deception. Although relatively little studied, this capability
      probably rivals cognitive abilities for language.

PMID- 22978770
TI  - Anticoagulation bridging around device surgery: compliance with guidelines.
AB  - BACKGROUND: Current guidelines recommend bridging anticoagulation in patients
      undergoing cardiac rhythm device surgery with a "moderate to high risk" of
      thromboembolism. Patients at "low risk" are advised to stop oral anticoagulation
      without bridging to the procedure. This study examines real world adherence to
      accepted guidelines and the clinical sequelae of nonadherence. METHODS: We
      performed a review of all patients undergoing device surgery receiving chronic
      anticoagulation over a prespecified time period of 14 months. Patients were
      classified per American College of Chest Physician guidelines as "moderate/high
      risk" or "low risk" of thromboembolism. We then compared perioperative management
      of anticoagulation to guideline recommendations and assessed the rate of
      perioperative bleeding and thromboembolism. RESULTS: One hundred and twenty-nine
      patients were included in this study. Sixty-two (48%) were classified as
      "moderate/high risk" and 67 (52%) "low risk." In the "moderate/high risk" group
      47/62 (76%) received perioperative anticoagulation but only 25/62 (40%) were
      bridged both pre- and postprocedure or maintained on uninterrupted warfarin. In
      the "low risk" group, 22/67 (33%) received bridging therapy. Device pocket
      hematoma or perioperative bleeding occurred in 10/129 (8%) with 4/10 receiving
      inappropriate bridging for a calculated low risk of thromboembolism. There were
      no perioperative thromboembolisms. CONCLUSIONS: Our study identified significant
      underutilization of bridging, particularly in the postoperative period, in
      patients at "moderate/high risk" of thromboembolism. Conversely, bridging was
      overused in "low risk" patients and associated with bleeding complications.
      Physicians should be urged to follow current expert guidelines in regard to
      bridging anticoagulation for cardiac rhythm device surgery. (PACE 2012;35:1480
      1486).

PMID- 22978771
TI  - Comparison of quetiapine and risperidone in Chinese Han patients with
      schizophrenia: results of a single-blind, randomized study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate
      (Seroquel) in the treatment of Chinese Han patients with schizophrenia. METHODS:
      In this 6-week, multicenter, randomized, rater single-blind study, a total of 119
      patients with schizophrenia were randomly assigned to quetiapine (n = 60, 750
      mg/day) or risperidone (n = 59, 4 mg/day). The efficacy was assessed by the
      Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Change
      (CGI-C) and the Calgary Depression Scale for Schizophrenia (CDSS). Safety and
      tolerability assessments included treatment-emergent adverse events, laboratory
      tests and electrocardiograms. RESULTS: The primary analysis demonstrated no
      significant difference between treatment in the two groups (quetiapine vs.
      risperidone: 31.9 +/- 17.5 vs. 33.3 +/- 17.3; P = 0.668). Improvements with both
      treatments were comparable for total PANSS, positive and negative subscores,
      general psychopathology subscales, and excitement and attack symptoms.
      Improvements in CGI-S were similar between treatment groups (P = 0.046). A more
      favorable trend was detected for quetiapine than risperidone in the reduction of
      CDSS scores from baseline, especially at week 1 (1.1 +/- 2.2 vs. 0.3 +/- 2.1, P <
      0.050). The rate of extrapyramidal symptom (EPS) and hyperprolactinemia-related
      adverse events was significantly lower in the quetiapine group than the
      risperidone group (13.3% vs. 43.3%, P < 0.001). Dizziness and somnolence were
      more common in the quetiapine group than the risperidone group. CONCLUSION:
      Quetiapine fumarate (750 mg/day) has broad clinical efficacy comparable to 4
      mg/day risperidone. Dizziness was common in the quetiapine group (P = 0.029), but
      the rate of somnolence was similar between the two groups (P = 0.114). EPS and
      hyperprolactinemia rates were significantly higher with risperidone (P < 0.001).
      Key limitations of this study include small sample size, short treatment periods,
      and no increase to 6 mg/day for risperidone because of its safety profile.

PMID- 22978772
TI  - Low-dose 7-day transdermal buprenorphine in daily clinical practice - perceptions
      of elderly patients with moderate non-malignant chronic pain.
AB  - OBJECTIVE: To assess patients' perceptions regarding the low-dose 7-day
      buprenorphine transdermal patch for treatment of moderate non-malignant chronic
      pain. METHODS: Patient-reported outcome data were collected in clinical practices
      in Germany in a prospective, multicenter, non-interventional observation using
      the German Pain Questionnaire/German Pain Diary. Questionnaires were completed by
      the patients without influence from the attending physician. Mean change in pain
      intensity (lowest, average, and highest pain intensity in the previous 24 h),
      changes in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), in
      impairments of daily activities (modified pain disability index, mPDI), in
      quality of life (quality of life impairment by pain inventory, QLIP), and in
      overall burden of pain over a 12-week treatment period were evaluated. RESULTS:
      Data of 891 patients were assessed (mean age 72.8 years). Buprenorphine starting
      doses were mainly 5 ug/h (67.1% of patients) and 10 ug/h (27.3%). At the end of
      week 12, the majority received either 5 ug/h (41%) or 10 ug/h (42.3%)
      buprenorphine. Mean average pain intensity was reduced by 5.1 points to 1.7 +/-
      1.3 from 6.8 +/- 1.5 points at baseline (76% improvement). Amelioration was
      observed in HADS-A (59% from 7.8 +/- 3.3 at baseline) and HADS-D (56% from 9.2 +/
      3.1), in mPDI sum score (76%; from 31.1 +/- 9.8), and in quality of life (165%;
      from 13.9 +/- 10.1). Mean burden of pain continuously decreased. LIMITATIONS: All
      those inherent in open-label observations and pain studies using subjective and
      patient-reported outcome parameters (such as the lack of a control group).
      CONCLUSIONS: Our results indicate that the 7-day buprenorphine patch might be
      considered an effective treatment option for moderate non-malignant chronic pain
      management in daily clinical practice. The mostly elderly patient population of
      this patient survey experienced sustained pain relief and improvements in pain
      related impairments of daily activities and quality of life, leading to a
      substantial reduction in overall burden of pain.

PMID- 22978773
TI  - Variation in the use of biologics in the management of rheumatoid arthritis
      across the UK.
AB  - OBJECTIVES: Treatment options for rheumatoid arthritis (RA) include conventional
      synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic
      DMARDs (biologics). This study describes treatment patterns, adherence to
      guidance and outcomes at hospital/regional level in the UK. METHODS: This was a
      retrospective cohort study of RA patients selected from six health regions and
      from four hospitals in each region, including at least one major teaching
      hospital and two to three district/general hospitals. Treatment with
      sDMARDs/biologics was examined between November 2009 and June 2010 in comparison
      with National Institute for Health and Clinical Excellence (NICE) guidance and in
      relation to disease activity. RESULTS: NICE guidance focuses on initiation of
      therapy and recommends combination sDMARD/biologic therapy. Analysis of 588
      patient records indicates that overall 23% of patients were receiving biologic
      monotherapy. NICE guidance recommends initiation of biologics in patients with
      active RA (DAS28 >5.1): average DAS28 score on initiation of biologic therapy was
      above six in all regions. Range of DAS28 improvement post-biologic therapy was
      similar across all regions. DAS28 scores were well recorded within patient
      records at baseline and 6 months but not at other time points. CONCLUSIONS: Our
      data highlight that nearly a quarter of patients receiving biologic treatments
      are not receiving concomitant sDMARD therapy and that DAS28 is poorly documented
      in patient medical records other than when initiating biologics and at the 6
      month review. Limitations of this study include the limited sample size, the
      retrospective rather than prospective nature of the audit and the use of medical
      records only rather than other records such as nursing and pharmacy data.
      Nevertheless, the reasons for our findings merit further investigation to ensure
      that optimum treatment regimes and long term outcomes are being achieved for
      patients.

PMID- 22978774
TI  - Publication misconduct and plagiarism retractions: a systematic, retrospective
      study.
AB  - OBJECTIVES: To investigate whether plagiarism is more prevalent in publications
      retracted from the medical literature when first authors are affiliated with
      lower-income countries versus higher-income countries. Secondary objectives
      included investigating other factors associated with plagiarism (e.g., national
      language of the first author's country affiliation, publication type, journal
      ranking). DESIGN: Systematic, controlled, retrospective, bibliometric study. DATA
      SOURCE: Retracted publications dataset in MEDLINE (search filters: English,
      human, January 1966-February 2008). DATA SELECTION: Retracted misconduct
      publications were classified according to the first author's country affiliation,
      country income level, and country national language, publication type, and
      ranking of the publishing journal. Standardised definitions and data collection
      tools were used; data were analysed (odds ratio [OR], 95% confidence limits [CL],
      chi-squared tests) by an independent academic statistician. RESULTS: Of the 213
      retracted misconduct publications, 41.8% (89/213) were retracted for plagiarism,
      52.1% (111/213) for falsification/fabrication, 2.3% (5/213) for author disputes,
      2.3% (5/213) for ethical issues, and 1.4% (3/213) for unknown reasons. The OR
      (95% CL) of plagiarism retractions (other misconduct retractions as reference)
      were higher (P < 0.001) for first authors affiliated with lower-income versus
      higher-income countries (15.4 [4.5, 52.9]) and with non-English versus English
      national language countries (3.2 [1.8, 5.7]), for non-original research versus
      original research publications (8.4 [3.3, 21.3]), for case reports and series
      versus other original research types (4.2 [1.4, 13.0]), and for publications in
      low-ranked versus high-ranked journals (4.9 [2.4, 9.9]). Up until 2012, there
      were significantly (P < 0.007) fewer 'serial offenders' (first authors with >1
      retraction) with publications retracted for plagiarism (11.5%, 9/78) than other
      types of misconduct (28.9%, 24/83). CONCLUSIONS: This is the first study to
      demonstrate that publications retracted for plagiarism are significantly
      associated with first authors affiliated with lower-income countries. These
      findings have implications for developing appropriate evidence-based strategies
      and allocation of resources to help mitigate plagiarism misconduct.

PMID- 22978775
TI  - Maintenance therapy of gefitinib for non-small-cell lung cancer after first-line
      chemotherapy regardless of epidermal growth factor receptor mutation: a review in
      Chinese patients.
AB  - PURPOSE: Gefitinib is a well known therapy for non-small-cell lung cancer
      (NSCLC). The purpose of this study was to review clinical reports of gefitinib as
      maintenance therapy after first-line chemotherapy regardless of epidermal growth
      factor receptor (EGFR) mutation, and assess its efficacy and safety in Chinese
      patients. MATERIALS AND METHODS: Systematic computerized searches of the
      following databases were conducted from the start of each database up to July
      2012; these include Medline, EMBASE, CNKI and www.clinicaltrials.gov. Terms
      searched include 'non-small-cell lung cancer', 'NSCLC', 'lung cancer', 'lung
      tumor', 'gefitinib', 'Iressa', 'EGFR' and 'epidermal growth factor receptor
      tyrosine kinase inhibitors'. A total of 22 studies were reviewed. RESULTS: In
      general, the overall response rate (ORR), disease control rate (DCR) and one year
      survival (OYS) of gefitinib maintenance therapy were 30.89%, 67.5% and 50.6%
      respectively, in addition, the median overall survival (OS) and median
      progression free survival (PFS) were 13.09 and 7.88 months respectively.
      Moreover, ORR, DCR, median survival time (MST) and PFS of female, nonsmoking,
      lung adenocarcinoma (LAC) patients and patients with rash had higher performance
      than male, smoking, non-LAC patients and patients without rash (p < 0.05). The
      adverse events (AEs) were mainly skin rashes and diarrhea, most of which were
      grades 1 or 2 and were well tolerated. CONCLUSION: Gefitinib produced encouraging
      efficacy, safety and survival when delivered as maintenance therapy for NSCLC in
      Chinese patients after first-line chemotherapy regardless of EGFR mutation,
      especially for the patients who were female, non-smokers, LAC and with rash. Key
      limitations of this review include limited subgroup data, small sample sizes, and
      the lack of EGFR/KRAS data.

PMID- 22978776
TI  - Osteoporosis. Letter to the editor.

PMID- 22978777
TI  - Are fixed-dose combination antihypertensives suitable as first-line therapy?
AB  - OBJECTIVE: To contemplate how initial antihypertensive therapy with fixed-dose
      combinations (FDC) might be incorporated into clinical practice, based on a
      compilation of evidence comparing FDCs with monotherapy and loose-dose
      combinations in varying patient populations. METHODS: A non-systematic search of
      PubMed (from 2007 to 2012) was performed for randomized, controlled trials in
      order to capture the evidence on FDC versus monotherapy and loose-dose
      combinations as first-line therapy. The literature search focused on calcium
      channel blocker (CCB)-renin angiotensin system (RAS) blocker combinations.
      Additionally, any relevant papers known to the authors were included.
      International recommendations from published hypertension treatment guidelines
      were also consulted. RESULTS: The results of this literature review identified
      two emergent issues. Firstly, there is a discord between antihypertensive use and
      actual blood pressure (BP) control achieved - despite an increase in the use of
      antihypertensives over the last 10 years, BP control rates remain low. Secondly,
      a greater association between BP and cardiovascular risk in Asians may magnify
      this discrepancy. A number of international guidelines are recommending early
      combination therapy, such as CCB-RAS blocker combinations in the majority of
      patients based on the available evidence, with such combinations showing benefits
      in terms of compliance, BP lowering and control, and safety. Additionally, recent
      studies have indicated that improved BP control may be achieved with simplified
      guidelines and the use of FDCs. Overall, these findings indicate that FDC could
      be used as first-line. CONCLUSIONS: The findings from this literature review
      suggest that physicians may need to readdress their approach to antihypertensive
      treatment. Earlier use of antihypertensive FDC (including first-line) may help to
      shrink the current gap between antihypertensive use and BP target control
      achieved. Most guidelines acknowledge that combination therapy is required in the
      majority of patients, and FDC are regarded as a suitable alternative, having
      demonstrated better compliance compared with loose-dose combinations.

PMID- 22978778
TI  - Production of copolyesters of 3-hydroxybutyrate and medium-chain-length 3
      hydroxyalkanoates by E. coli containing an optimized PHA synthase gene.
AB  - BACKGROUND: Microbial polyhydroxyalkanoates (PHA) are biopolyesters consisting of
      diverse monomers. PHA synthase PhaC2Ps cloned from Pseudomonas stutzeri 1317 is
      able to polymerize short-chain-length (scl) 3-hydroxybutyrate (3HB) monomers and
      medium-chain-length (mcl) 3-hydroxyalkanoates (3HA) with carbon chain lengths
      ranging from C6 to C12. However, the scl and mcl PHA production in Escherichia
      coli expressing PhaC2Ps is limited with very low PHA yield. RESULTS: To improve
      the production of PHA with a wide range of monomer compositions in E. coli, a
      series of optimization strategies were applied on the PHA synthase PhaC2Ps. Codon
      optimization of the gene and mRNA stabilization with a hairpin structure were
      conducted and the function of the optimized PHA synthase was tested in E. coli.
      The transcript was more stable after the hairpin structure was introduced, and
      western blot analysis showed that both codon optimization and hairpin
      introduction increased the protein expression level. Compared with the wild type
      PhaC2Ps, the optimized PhaC2Ps increased poly-3-hydroxybutyrate (PHB) production
      by approximately 16-fold to 30% of the cell dry weight. When grown on
      dodecanoate, the recombinant E. coli harboring the optimized gene phaC2PsO with a
      hairpin structure in the 5' untranslated region was able to synthesize 4-fold
      more PHA consisting of 3HB and medium-chain-length 3HA compared to the
      recombinant harboring the wild type phaC2Ps. CONCLUSIONS: The levels of both PHB
      and scl-mcl PHA in E. coli were significantly increased by series of optimization
      strategies applied on PHA synthase PhaC2Ps. These results indicate that
      strategies including codon optimization and mRNA stabilization are useful for
      heterologous PHA synthase expression and therefore enhance PHA production.

PMID- 22978779
TI  - General practitioners' views on quality markers for children in UK primary care:
      a qualitative study.
AB  - BACKGROUND: Children make up about 20% of the UK population and caring for them
      is an important part of a general practitioner's (GP's) workload. However, the UK
      Quality Outcomes Framework (pay-for-performance system) largely ignores children 
      less than 3% of the quality markers relate to them. As no previous research has
      investigated whether GPs would support or oppose the introduction of child
      specific quality markers, we sought their views on this important question.
      METHODS: Qualitative interview study with 20 GPs from four primary care trusts in
      Thames Valley, England. Semi-structured interviews explored GPs' viewpoints on
      quality markers and childhood conditions that could be developed into markers in
      general practice. Interviews were audiotaped and transcribed verbatim. Analysis
      was thematic and used constant comparative method to look for anticipated and
      emergent themes as the analysis progressed. RESULTS: All the GPs interviewed
      supported the development of 'benchmarks' or 'standards' to measure and improve
      quality of care for children. However no consensus was expressed about the
      clinical conditions for which quality markers should be developed. Many
      participants reflected on their concerns about unmet health care needs and felt
      there may be opportunities to improve proactive care in 'at risk' groups. Some
      expressed feelings of powerlessness that important child-relevant outcomes such
      as emergency department visits and emergency admissions were out of their control
      and more directly related to public health, school and parents/carers. The
      importance of access was a recurrent theme; access to urgent general practice
      appointments for children and GP access to specialists when needed. CONCLUSION:
      The GPs expressed support for the development of quality markers for the care of
      children in UK general practice. However, they flagged up a number of important
      challenges which need to be addressed if markers are to be developed that are
      measureable, targeted and within the direct control of primary care. Easy access
      to primary and secondary care appointments may be an important benchmark for
      commissioners of care.

PMID- 22978781
TI  - Adsorption and desorption of bis-(3-sulfopropyl) disulfide during Cu
      electrodeposition and stripping at Au electrodes.
AB  - The adsorption and desorption of bis-(3-sulfopropyl) disulfide (SPS) on Cu and Au
      electrodes and its electrochemical effect on Cu deposition and dissolution were
      examined using cyclic voltammetry stripping (CVS), field-emission scanning
      electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). SPS
      dissociates into 3-mercapto-1-propanesulfonate when it is contacted with Au and
      Cu electrodes, producing Cu(I)- and Au(I)-thiolate species. These thiolates
      couple with chloride ions and promote not only the reduction of Cu(2+) in Cu
      deposition but also the oxidation of Cu(0) to Cu(+) in Cu stripping. During Cu
      electrodeposition on the SPS-modified Au electrode, thiolates transfer from Au
      onto the Cu underpotential deposition (UPD) layer. The Cu UPD layer stabilizes a
      large part of the transferred thiolates which subsequently is buried by the Cu
      overpotential deposition (OPD) layer. The buried thiolates reappear on the Au
      electrode after the copper deposit is electrochemically stripped off. A much
      smaller part of thiolates transfers to the top of the Cu OPD layer. In contrast,
      when SPS preadsorbs on a Cu-coated Au electrode, almost all of the adsorbed SPS
      leaves the Cu surface during Cu electrochemical stripping and does not return to
      the uncovered Au surface. A reaction mechanism is proposed to explain these
      results.

PMID- 22978780
TI  - A predictive tool for an effective use of (18)F-FDG PET in assessing activity of
      sarcoidosis.
AB  - BACKGROUND: (18)F-FDG PET/CT (PET) is useful in assessing inflammatory activity
      in sarcoidosis. However, no appropriate indications are available. The aim of
      this study was to develop a prediction rule that can be used to identify
      symptomatic sarcoidosis patients who have a high probability of PET-positivity.
      METHODS: We retrospectively analyzed a cohort of sarcoidosis patients with non
      organ specific persistent disabling symptoms (n = 95). Results of soluble
      interleukin-2 receptor (sIL-2R) assessment and high-resolution computed
      tomography (HRCT) were included in the predefined model. HRCT scans were
      classified using a semi-quantitative scoring system and PET findings as positive
      or negative, respectively. A prediction model was derived based on logistic
      regression analysis. We quantified the model's performance using measures of
      discrimination and calibration. Finally, we constructed a prediction rule that
      should be easily applicable in clinical practice. RESULTS: The prediction rule
      showed good calibration and good overall performance (goodness-of-fit test, p =
      0.78, Brier score 20.1%) and discriminated between patients with positive and
      negative PET findings (area under the receiver-operating characteristic curve,
      0.83). If a positive predictive value for the presence of inflammatory activity
      of >=90% is considered acceptable for clinical decision-making without referral
      to PET, PET would be indicated in only 29.5% of the patients. Using a positive
      predictive value of 98%, about half of the patients (46.3%) would require
      referral to PET. CONCLUSIONS: The derived and internally validated clinical
      prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be
      useful to identify sarcoidosis patients with a high probability of inflammatory
      activity. Using this rule may enable a more effective use of PET scan for
      assessment of inflammatory activity in sarcoidosis.

PMID- 22978782
TI  - Molecular characterization of oxacillinases and genotyping of invasive
      Acinetobacter baumannii isolates using repetitive extragenic palindromic sequence
      based polymerase chain reaction in Ankara between 2004 and 2010.
AB  - BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDRAB) is an increasing
      problem worldwide. We aimed to determine the antibiotic susceptibility, diversity
      of oxacillinases, and molecular types of MDRAB. METHODS: A total of 100 non
      duplicate A. baumannii blood culture isolates were evaluated. Antimicrobial
      susceptibilities of the isolates were determined according to the standard
      Clinical and Laboratory Standards Institute (CLSI) broth microdilution method.
      Colistin, doripenem, and tigecycline susceptibilities were analyzed by E-test.
      The presence of bla(OXA-23-like), bla(OXA-24-like), bla(OXA-51-like), and bla(OXA
      58-like) genes was investigated by multiplex polymerase chain reaction (PCR).
      Typing of A. baumannii isolates was performed using repetitive extragenic
      palindromic sequence-based PCR (rep-PCR; DiversiLab). RESULTS: Most isolates were
      susceptible to colistin (98% susceptible) and tigecycline (94% susceptible),
      whereas fewer isolates were susceptible to imipenem, meropenem, and doripenem
      (17%, 17%, and 18% susceptible, respectively). Carbapenem resistance was
      associated with the presence of bla(OXA-23-like) (31% of isolates) and bla(OXA-58
      like) (23% of isolates) genes. The occurrence of isolates carrying bla(OXA-58
      like) genes increased between y 2004 and 2009, but decreased in 2010. In
      contrast, isolates with bla(OXA-23-like) genes increased during the 2008-2010
      period. Out of 100 isolates, 62 were categorized into 13 major rep-PCR patterns,
      with the highest prevalence in pattern 1 (10 isolates), followed by patterns 2
      and 3 (9 isolates each). CONCLUSIONS: Carbapenem-resistant invasive A. baumannii
      isolates carrying the bla(OXA-23-like) gene became more prevalent and replaced
      isolates carrying the bla(OXA-58-like) carbapenemase gene through the 7 y. Rep
      PCR genotyping of these strains confirmed that ongoing MDRAB resulted from a long
      term persistence and mixture of several clusters.

PMID- 22978783
TI  - Comparative analysis of two antifungal Lactobacillus plantarum isolates and their
      application as bioprotectants in refrigerated foods.
AB  - AIMS: To compare the technological robustness of two antifungal Lactobacillus
      plantarum isolates and to assess their ability to inhibit growth of the spoilage
      yeast Rhodotorula mucilaginosa in two different refrigerated foods. METHODS AND
      RESULTS: The effects of freeze-drying, thermal treatments and varying salt
      concentrations on the viability of two antifungal lactic acid bacteria (LAB) were
      examined. Antifungal compound(s) contained in the supernatant of both isolates
      were compared to commercially available food preservatives. Both isolates were
      used as dairy starter adjuncts in yoghurt and inoculants in orange juice to
      determine the antiyeast activity towards R. mucilaginosa. Yeast growth was
      retarded by the tested isolates in both food settings with one of the isolates,
      Lact. plantarum 16, being the most potent inhibitor. CONCLUSIONS: Both
      lactobacilli exhibited considerable robustness to withstand processing treatments
      commonly encountered in a food industrial setting. The isolates were shown to
      possess potent antifungal activity in both in vivo and in vitro food models.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The studied antifungal lactobacilli may
      represent safer and consumer-friendly alternatives to the use of chemical
      preservatives. This is the first report of antifungal Lact. plantarum exerting
      protective potential in yoghurt and orange juice.

PMID- 22978784
TI  - All-atom stability and oligomerization simulations of polyglutamine nanotubes
      with and without the 17-amino-acid N-terminal fragment of the Huntingtin protein.
AB  - Several neurodegenerative diseases are associated with the polyglutamine (polyQ)
      repeat disorder in which a segment of consecutive glutamines in the native
      protein is produced with too many glutamines. Huntington's disease, for example,
      is related to the misfolding of the Huntingtin protein which occurs when the
      polyQ segment has more than approximately 36 glutamines. Experimentally, it is
      known that the polyQ segment alone aggregates into beta-rich conformations such
      as amyloid fibrils. Its aggregation is modulated by the number of glutamine
      residues as well as by the surrounding amino acid sequences such as the 17-amino
      acid N-terminal fragment of Huntingtin which increases the aggregation rate.
      Little structural information is available, however, regarding the first steps of
      aggregation and the atomistic mechanisms of oligomerization are yet to be
      described. Following previous coarse-grained replica-exchange molecular dynamics
      simulations that show the spontaneous formation of a nanotube consisting of two
      intertwined antiparallel strands (Laghaei, R.; Mousseau, N. J. Chem. Phys. 2010,
      132, 165102), we study this configuration and some extensions of it using all
      atom explicit solvent MD simulations. We compare two different lengths for the
      polyQ segment, 40 and 30 glutamines, and we investigate the impact of the
      Huntingtin N-terminal residues (htt(NT)). Our results show that the dimeric
      nanotubes can provide a building block for the formation of longer nanotubes
      (hexamers and octamers). These longer nanotubes are characterized by large beta
      sheet propensities and a small solvent exposure of the main-chain atoms.
      Moreover, the oligomerization between two nanotubes occurs through the formation
      of protein/protein H-bonds and can result in an elongation of the water-filled
      core. Our results also show that the htt(NT) enhances the structural stability of
      the beta-rich seeds, suggesting a new mechanism by which it can increase the
      aggregation rate of the amyloidogenic polyQ sequence.

PMID- 22978785
TI  - Accounting for changes in particle charge, dry mass and composition occurring
      during studies of single levitated particles.
AB  - The most used instrument in single particle hygroscopic analysis over the past
      thirty years has been the electrodynamic balance (EDB). Two general assumptions
      are made in hygroscopic studies involving the EDB. First, it is assumed that the
      net charge on the droplet is invariant over the time scale required to record a
      hygroscopic growth cycle. Second, it is assumed that the composition of the
      droplet is constant (aside from the addition and removal of water). In this
      study, we demonstrate that these assumptions cannot always be made and may indeed
      prove incorrect. The presence of net charge in the humidified vapor phase reduces
      the total net charge retained by the droplet over prolonged levitation periods.
      The gradual reduction in charge limits the reproducibility of hygroscopicity
      measurements made on repeated RH cycles with a single particle, or prolonged
      experiments in which the particle is held at a high relative humidity. Further,
      two contrasting examples of the influence of changes in chemical composition
      changes are reported. In the first, simple acid-base chemistry in the droplet
      leads to the irreversible removal of gaseous ammonia from a droplet containing an
      ammonium salt on a time scale that is shorter than the hygroscopicity
      measurement. In the second example, the net charge on the droplet (<100 fC) is
      high enough to drive redox chemistry within the droplet. This is demonstrated by
      the reduction of iodic acid in a droplet made solely of iodic acid and water to
      form iodine and an iodate salt.

PMID- 22978786
TI  - A structure-function relationship for the optical modulation of phenyl boronic
      acid-grafted, polyethylene glycol-wrapped single-walled carbon nanotubes.
AB  - Phenyl boronic acids (PBA) are important binding ligands to pendant diols useful
      for saccharide recognition. The aromatic ring can also function to anchor an
      otherwise hydrophilic polymer backbone to the surface of hydrophobic graphene or
      carbon nanotube. In this work, we demonstrate both functions using a homologous
      series of seven phenyl boronic acids conjugated to a polyethylene glycol, eight
      membered, branched polymer (PPEG8) that allows aqueous dispersion of single
      walled carbon nanotubes (SWNT) and quenching of the near-infrared fluorescence in
      response to saccharide binding. We compare the 2-carboxyphenylboronic acid
      (2CPBA); 3-carboxy- (3CPBA) and 4-carboxy- (4CPBA) phenylboronic acids; N-(4
      phenylboronic)succinamic acid (4SCPBA); 5-bromo-3-carboxy- (5B3CPBA), 3-carboxy-5
      fluoro- (5F3CPBA), and 3-carboxy-5-nitro- (5N3CPBA) phenylboronic acids,
      demonstrating a clear link between SWNT photoluminescence quantum yield and
      boronic acid structure. Surprisingly, quantum yield decreases systematically with
      both the location of the BA functionality and the inclusion of electron
      withdrawing or -donating substituents on the phenyl ring. For three structural
      isomers (2CPBA, 3CPBA, and 4CPBA), the highest quantum yields were measured for
      para-substituted PBA (4CPBA), much higher than ortho- (2CPBA) and meta- (3CPBA)
      substituted PBA, indicating the first such dependence on molecular structure.
      Electron-withdrawing substituents such as nitro groups on the phenyl ring cause
      higher quantum yield, while electron-donating groups such as amides and alkyl
      groups cause a decrease. The solvatochromic shift of up to 10.3 meV was used for
      each case to estimate polymer surface coverage on an areal basis using a linear
      dielectric model. Saccharide recognition using the nIR photoluminescence of SWNT
      is demonstrated, including selectivity toward pentoses such as arabinose, ribose,
      and xylose to the exclusion of the expected fructose, which has a high
      selectivity on PBA due to the formation of a tridentate complex between fructose
      and PBA. This study is the first to conclusively link molecular structure of an
      adsorbed phase to SWNT optical properties and modulation in a systematic manner.

PMID- 22978787
TI  - Therapeutic imprinting of the immune system: towards a remission of AIDS in
      primates?
AB  - Our inability to cure HIV/AIDS is related to the ability of the virus to
      establish reservoirs during treatment. In order to develop new strategies, it is
      certainly essential that a suitable animal model be implemented. In the recent
      work of Shytaj et al., it has been possible to inhibit viral replication to
      levels below the assay detection limit in the macaque AIDS model. Moreover,
      different therapeutic regimens applied to the rhesus macaque AIDS model (herein
      reviewed), including ours, are starting to show the potential to induce,
      following therapy suspension, conditions reminiscent of a drug-free control of
      the infection.

PMID- 22978788
TI  - Non-destructive characterisation and classification of ceramic artefacts using
      pEDXRF and statistical pattern recognition.
AB  - BACKGROUND: Portable energy dispersive X-ray fluorescence (pEDXRF) spectrometry
      analysis was applied for the characterisation of archaeological ceramic findings
      from three Neolithic sites in Serbia. Two dimension reduction techniques,
      principal component analysis (PCA) and scattering matrices-based dimension
      reduction were used to examine the possible classification of those findings, and
      to extract the most discriminant features. RESULTS: A decision-making procedure
      is proposed, whose goal is to classify unknown ceramic findings based on their
      elemental compositions derived by pEDXRF spectrometry. As a major part of
      decision-making procedure, the possibilities of two dimension reduction methods
      were tested. Scattering matrices-based dimension reduction was found to be the
      more efficient method for the purpose. Linear classifiers designed based on the
      desired output allowed for 7 of 8 unknown samples from the test set to be
      correctly classified. CONCLUSIONS: Based on the results, the conclusion is that
      despite the constraints typical of the applied analytical technique, the
      elemental composition can be considered as viable information in provenience
      studies. With a fully-developed procedure, ceramic artefacts can be classified
      based on their elemental composition and well-known provenance.

PMID- 22978789
TI  - Apoptotic vascular smooth muscle cell depletion via BCL2 family of proteins in
      human ascending aortic aneurysm and dissection.
AB  - AIMS: This study investigates the expression patterns of BCL2 (B-cell
      CLL/lymphoma2) family of proteins and the extent of vascular smooth muscle cell
      (VSMC) apoptosis in thoracic aortic aneurysms (TAA), type-A aortic dissections
      (TAD), and nondilated ascending aortic samples. METHODS: Aortic wall specimens
      were obtained from patients undergoing surgical repair for TAA (n = 24), TAD (n =
      20), and normal aortic tissues from organ donors (n = 6). The expression pattern
      of BCL2, BCL2L1 (BCL2-like1), BAK1 (BCL2-antagonist/killer1), and BAX (BCL2
      associated X protein) proteins was investigated by immunohistochemistry.
      Furthermore, colocalization of alpha smooth muscle actin (ACTA2) and caspase3
      (CASP3) in aortic VSMCs was analyzed by double-immunofluorescence staining. Onset
      of DNA fragmentation was measured by TUNEL assay. RESULTS: Apoptotic index was
      significantly increased in both TAD group (31.3 +/- 17.2, P < 0.001) and TAA
      group (21.1 +/- 12.7, P = 0.001) relative to control aortas (2.0 +/- 1.2). Anti
      CASP3 and ACTA2 double-immunostaining confirmed apoptosis in VSMCs in TAA and TAD
      groups but not in controls. Proapoptotic BAX expression was significantly
      elevated in VSMCs of TAA patients, compared with that of controls (OR = 20; P =
      0.02; 95% CI, 16-250). In contrast, antiapoptotic BCL2L1 expression was higher in
      controls compared with that of TAA group (OR = 11.2; P = 0.049; 95% CI, 1.0
      123.9). Furthermore, BAX/BCL2 ratio was significantly increased in both TAA (1.2
      +/- 0.7, P < 0.001) and TAD (0.6 +/- 0.4, P = 0.05) groups relative to controls
      (0.2 +/- 0.1, P < 0.001). CONCLUSIONS: Apoptotic VSMC depletion in human TAA/TAD
      is associated with disturbance of the balance between proapoptotic and
      antiapoptotic members of the BCL2 family proteins, which may have a role in the
      pathogenesis of vascular remodelling in aortic disease. In light of the future
      studies, targeting apoptotic pathways in TAA and TAD pathogenesis may provide
      therapeutic benefits to patients by slowing down the progression and even
      possibly preventing the TAD.

PMID- 22978790
TI  - Enantioselective total synthesis of (+)-lithospermic acid.
AB  - An enantioselective synthesis of (+)-lithospermic acid, a potent anti-HIV agent,
      has been accomplished in a convergent manner in nine steps. The synthesis
      features an enantioselective intramolecular oxa-Michael addition catalyzed by a
      quinidine derivative, a hypervalent iodine-mediated rearrangement of chromanone
      to dihydrobenzofuran, an enantioselective alpha-oxyamination, and an
      intermolecular C-H olefination.

PMID- 22978791
TI  - Wireless 'mini' multichannel intraluminal impedance-pH: what is the optimal
      design of a miniature wireless device?
AB  - Catheter-based methods for multichannel intraluminal impedance-pH monitoring are
      invasive and uncomfortable. The current alternative is a wireless system that
      clips to the esophageal mucosa, but which only measures pH. A shorter two-site
      wireless sensor that detects impedance and pH, and can be clipped to the
      esophagus, would be desirable. This study compares sensor positions and
      separations to determine the optimal configuration of a two-site wireless sensor.
      Records of 20 patients (10 on and 10 off proton pump inhibitor) who had
      ambulatory reflux testing with a multichannel intraluminal impedance-pH system
      (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two
      pH sensors were reviewed. An investigator was blinded to four combinations of
      impedance channels plus pH. He read a 3-hour postprandial section from each of
      the combinations (total of 80 studies) and marked reflux episodes. Results were
      compared with his own interpretation of the full tracing. Two hundred and two
      total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4).
      Mean and median numbers of total reflux episodes were calculated. In the full
      study, the interpreter detected a mean of 10 reflux episodes per study. In the 5
      cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a
      mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One-way
      analysis of variance yielded a P-value of 0.43. The trend of these preliminary
      findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm
      and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred
      location. The lack of a significant difference, at the very least, suggests that
      any of the 'mini' locations could be used. The small number of observations could
      have resulted in a Type II statistical error. 

PMID- 22978792
TI  - Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma
      cells.
AB  - CONTEXT: Cancer is a disease characterized by abnormal growth of cells. One of
      the most common types of liver cancers is called hepatocellular carcinoma (HCC)
      which is highly metastatic. As most of cannabinoids have shown anticancer effect
      against different cell lines in a number of reports, a biological investigation
      of two cannabinoids, CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist)
      was carried out in this study. OBJECTIVE: In an attempt to find natural products
      as a new solution of cancer, this study was designed to investigate the potential
      antitumoral and anti-invasive activity of cannabinoids on HepG2 cells and the
      possible roles of matrix metalloproteinase-2 (MMP-2) and MMP-9 in its action.
      MATERIALS AND METHODS: The researchers examined the effect of various
      concentrations of CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist), on
      the cell proliferation, viability, and invasion as well as expression of MMP-2
      and MMP-9 in HepG2 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliumbromide (MTT) assay, matrigel invasion assay, and western
      blotting method. RESULTS: The results revealed that both cannabinoids reduce cell
      viability, cell invasion as well as MMP-2 and MMP-9 expression in higher dose of
      20 nM. Furthermore, higher concentrations of examined cannabinoids were more
      effective. DISCUSSION: These data suggest ACEA and CB65 as an option for novel
      treatment of hepatocellular cancer. CONCLUSION: Our findings may contribute to
      design of new therapeutic strategies for the management of HCC.

PMID- 22978793
TI  - Assisted reproductive techniques and the risk of anorectal malformations: a
      German case-control study.
AB  - BACKGROUND: The use of assisted reproductive techniques (ART) for treatment of
      infertility is increasing rapidly worldwide. However, various health effects have
      been reported including a higher risk of congenital malformations. Therefore, we
      assessed the risk of anorectal malformations (ARM) after in-vitro fertilization
      (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: Data of the German
      Network for Congenital Uro-REctal malformations (CURE-Net) were compared to
      nationwide data of the German IVF register and the Federal Statistical Office
      (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify
      associations using multivariable logistic regression accounting for potential
      confounding or interaction by plurality of births. RESULTS: In total, 295 ARM
      patients born between 1997 and 2011 in Germany, who were recruited through
      participating pediatric surgeries from all over Germany and the German self-help
      organisation SoMA, were included. Controls were all German live-births (n =
      10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982
      controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95%
      confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses.
      Separate analyses showed a significantly increased risk for ARM after IVF (OR,
      10.9; 95% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6
      12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM,
      ARM with associated anomalies and those with a VATER/VACTERL association showed
      strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After
      stratification for plurality of birth, the corresponding odds ratios (95%
      confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for
      multiple births. CONCLUSIONS: There is a strongly increased risk for ARM among
      children born after ART. Elevations of risk were seen after both IVF and ICSI.
      Further, separate analyses of patients with isolated ARM, ARM with associated
      anomalies and those with a VATER/VACTERL association showed increased risks in
      each group. An increased risk of ARM was also seen among both singletons and
      multiple births.

PMID- 22978794
TI  - Fast and efficient online release of N-glycans from glycoproteins facilitating
      liquid chromatography-tandem mass spectrometry glycomic profiling.
AB  - A novel online enzyme reactor incorporating peptide-N-glycosidase F (PNGase F) on
      a monolithic polymer support has been developed to allow the rapid simultaneous
      release of both neutral and acidic N-linked glycans from glycoproteins. The
      PNGase F monolithic reactor was fabricated in a fused silica using glycidyl
      methacrylate-co-ethylene dimethacrylate polymer. The reactor was coupled to a C8
      trap and a porous graphitic carbon (PGC) HPLC-chip. This arrangement was
      interfaced to an ion trap mass spectrometer for liquid chromatography-mass
      spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS) analyses. The performance of the PNGase F reactor was optimized using the
      MS signal for the disialylated biantennary N-glycan derived from fetuin. Optimum
      conditions for glycan release were attained at room temperature using a loading
      flow rate of 2 MUL/min and a reaction time of 6 min. The loading capacity of the
      reactor was determined to be around 2 pmol of glycoprotein. The online digestion
      and MS characterization experiments resulted in sensitivities as high as 100 fmol
      of glycoprotein and 0.1 MUL of human blood serum. The enzyme reactor activity was
      also shown to remain stable after 1 month of continuous use. Both small and large
      glycoproteins as well as glycoproteins containing high-mannose glycans,
      fucolsylated glycans, sialylated glycans, and hybrid structures were studied. The
      model glycoproteins included ribonuclease B, fetuin, alpha(1)-acid glycoprotein,
      immunoglobulin, and thyroglobulin. All N-glycans associated with these model
      glycoproteins were detected using the online PNGase F reactor setup.

PMID- 22978795
TI  - Changes in type-specific human papillomavirus load predict progression to
      cervical cancer.
AB  - Persistent high-risk human papillomavirus (HPV) infection is strongly associated
      with the development of high-grade cervical intraepithelial neoplasia or cancer
      (CIN3+). However, HPV infection is common and usually transient. Viral load
      measured at a single time-point is a poor predictor of the natural history of HPV
      infection. The profile of viral load evolution over time could distinguish HPV
      infections with carcinogenic potential from infections that regress. A case
      cohort natural history study was set-up using a Belgian laboratory database
      processing more than 100,000 liquid cytology specimens annually. All cytology
      leftovers were submitted to real-time PCR testing identifying E6/E7 genes of 17
      HPV types, with viral load expressed as HPV copies/cell. Samples from untreated
      women who developed CIN3+ (n = 138) and women with transient HPV infection (n =
      601) who contributed at least three viral load measurements were studied. Only
      single-type HPV infections were selected. The changes in viral load over time
      were assessed by the linear regression slope for the productive and/or clearing
      phase of infection in women developing CIN3+ and women with transient infection
      respectively. Transient HPV infections generated similar increasing (0.21
      copies/cell/day) and decreasing (-0.28 copies/cell/day) viral load slopes. In HPV
      infections leading to CIN3+, the viral load increased almost linearly with a
      slope of 0.0028 copies/cell/day. Difference in slopes between transient
      infections and infections leading to CIN3+ was highly significant (P < .0001).
      Serial type-specific viral load measurements predict the natural history of HPV
      infections and could be used to triage women in HPV-based cervical cancer
      screening.

PMID- 22978796
TI  - Evidence on existing caries risk  assessment systems: are they  predictive of
      future caries?
AB  - AIM: To critically appraise evidence for the prediction of caries using four
      caries risk assessment (CRA) systems/guidelines (Cariogram, Caries Management by
      Risk Assessment (CAMBRA), American Dental Association (ADA), and American Academy
      of Pediatric Dentistry (AAPD)). This review focused on prospective cohort studies
      or randomized controlled trials. METHODS: A systematic search strategy was
      developed to locate papers published in Medline Ovid and Cochrane databases. The
      search identified 539 scientific reports, and after title and abstract review,
      137 were selected for full review and 14 met the following inclusion criteria:
      (i) used as validating criterion caries incidence/increment, (ii) involved human
      subjects and natural carious lesions, and (iii) published in peer-reviewed
      journals. In addition, papers were excluded if they met one or more of the
      following criteria: (i) incomplete description of sample selection, outcomes, or
      small sample size and (ii) not meeting the criteria for best evidence under the
      prognosis category of the Oxford Centre for Evidence-Based Medicine. RESULTS:
      There are wide variations among the systems in terms of definitions of caries
      risk categories, type and number of risk factors/markers, and disease indicators.
      The Cariogram combined sensitivity and specificity for predicting caries in
      permanent dentition ranges from 110 to 139 and is the only system for which
      prospective studies have been conducted to assess its validity. The Cariogram had
      limited prediction utility in preschool children, and a moderate to good
      performance for sorting out elderly individuals into caries risk groups. One
      retrospective analysis on CAMBRA's CRA reported higher incidence of cavitated
      lesions among those assessed as extreme-risk patients when compared with those at
      low risk. CONCLUSION: The evidence on the validity for existing systems for CRA
      is limited. It is unknown if the identification of high-risk individuals can lead
      to more effective long-term patient management that prevents caries initiation
      and arrests or reverses the progression of lesions. There is an urgent need to
      develop valid and reliable methods for caries risk assessment that are based on
      best evidence for prediction and disease management rather than opinions of
      experts.

PMID- 22978797
TI  - Hemoglobin-based oxygen carrier microparticles: synthesis, properties, and in
      vitro and in vivo investigations.
AB  - Bovine hemoglobin microparticles (Hb-MPs) as suitable oxygen carriers are
      fabricated easily by three key steps: coprecipitation of Hb and CaCO(3) to make
      Hb-CaCO(3)-microparticles (Hb-CaCO(3)-MPs), cross-linking by glutaraldehyde (GA)
      to polymerize the Hb and dissolution of CaCO(3) template to obtain pure Hb-MPs.
      The Hb entrapment efficiency ranged from 8 to 50% corresponding to a hemoglobin
      quantity per Hb-MP of at least one-third of that in one erythrocyte. The Hb-MPs
      are spherical, with an average diameter of 3.2 MUm and high oxygen affinity. The
      methemoglobin level was increased after preparation, but can be reduced to less
      than 7% with ascorbic acid. Phagocytosis assays showed low immunogenicity of Hb
      MPs if the particles were cross-linked with low concentration of GA and treated
      with sodium borohydride. Magnetite-loaded Hb-MPs circulated up to 4 days after
      intravenous application.

PMID- 22978798
TI  - An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase
      negative, non-fermentative Saccharomyces cerevisiae.
AB  - BACKGROUND: Pyruvate-decarboxylase negative (Pdc-) strains of Saccharomyces
      cerevisiae combine the robustness and high glycolytic capacity of this yeast with
      the absence of alcoholic fermentation. This makes Pdc-S. cerevisiae an
      interesting platform for efficient conversion of glucose towards pyruvate-derived
      products without formation of ethanol as a by-product. However, Pdc- strains
      cannot grow on high glucose concentrations and require C2-compounds (ethanol or
      acetate) for growth under conditions with low glucose concentrations, which
      hitherto has limited application in industry. RESULTS: Genetic analysis of a Pdc-
      strain previously evolved to overcome these deficiencies revealed a 225 p in
      frame internal deletion in MTH1, encoding a transcriptional regulator involved in
      glucose sensing. This internal deletion contains a phosphorylation site required
      for degradation, thereby hypothetically resulting in increased stability of the
      protein. Reverse engineering of this alternative MTH1 allele into a non-evolved
      Pdc- strain enabled growth on 20 g l-1 glucose and 0.3% (v/v) ethanol at a
      maximum specific growth rate (0.24 h-1) similar to that of the evolved Pdc-
      strain (0.23 h-1). Furthermore, the reverse engineered Pdc- strain grew on
      glucose as sole carbon source, albeit at a lower specific growth rate (0.10 h-1)
      than the evolved strain (0.20 h-1). The observation that overexpression of the
      wild-type MTH1 allele also restored growth of Pdc-S. cerevisiae on glucose is
      consistent with the hypothesis that the internal deletion results in decreased
      degradation of Mth1. Reduced degradation of Mth1 has been shown to result in
      deregulation of hexose transport. In Pdc- strains, reduced glucose uptake may
      prevent intracellular accumulation of pyruvate and/or redox problems, while
      release of glucose repression due to the MTH1 internal deletion may contribute to
      alleviation of the C2-compound auxotrophy. CONCLUSIONS: In this study we have
      discovered and characterised a mutation in MTH1 enabling Pdc- strains to grow on
      glucose as the sole carbon source. This successful example of reverse engineering
      not only increases the understanding of the glucose tolerance of evolved Pdc- S.
      cerevisiae, but also allows introduction of this portable genetic element into
      various industrial yeast strains, thereby simplifying metabolic engineering
      strategies.

PMID- 22978799
TI  - Significant reduction of atrial defibrillation threshold and inducibility by
      catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF)
      has antiarrhythmic effects by multiple mechanisms. We hypothesized that RFCA
      curtails atrial defibrillation threshold (A-DFT) and postablation induction
      pacing cycle length (iPCL), making critical mass reduction one potential
      mechanism by which antiarrhythmic effect is achieved. METHODS: We included 289
      patients with AF (male 77.9%, 55.7 +/- 10.8 years old; 197 paroxysmal AF: 92
      persistent AF) who underwent RFCA. A-DFT (serial internal cardioversion 2, 3, 5,
      7, and 10 J) and iPCL (serial 10 mA 10-second atrial pacing with pacing cycle
      length 250, 200, 190, 180, 170, 160, and 150 ms) were evaluated before and after
      RFCA. RESULTS: (1) RFCA of AF reduced the A-DFT from 6.7 +/- 3.7 J to 3.0 +/- 3.0
      J (P < 0.001). (2) AF ablation reduced AF inducibility from 95.4% before the
      procedure to 56.3% after the procedure (P < 0.001), and the iPCL from 194.8 +/-
      32.6 to 160.9 +/- 26.2 ms (P < 0.001). (3) In patients who underwent a greater
      number of ablation lines, the post-RFCA A-DFT (P < 0.001) was lower, and %DeltaA
      DFT (P = 0.003) and proportion of atrial tachycardia (P = 0.022) were higher than
      those with a lower number of ablation lines. CONCLUSION: AF ablation
      significantly reduced A-DFT, AF inducibility, and iPCL, and the degree of their
      reduction was related to the number of ablation lines. (PACE 2012;35:1428-1435).

PMID- 22978801
TI  - Transient Horner's syndrome after paravertebral brachial plexus blockade in a
      dog.

PMID- 22978800
TI  - Prevalence and factors associated with nonalcoholic fatty liver disease in
      Shanghai work-units.
AB  - BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) has become the most common
      chronic liver disease in Asians. However, data on prevalence and factors
      associated with NAFLD in Asians are lacking. The aim of this study is to
      investigate the prevalence of NAFLD in Shanghai employees to assess the
      relationship between NAFLD and age, gender, metabolic risk factors in this
      studied population. METHODS: We selected 7152 employees of Shanghai work-units.
      Each of them underwent detailed medical history-taking, physical examination,
      laboratory assessments and abdominal ultrasonography. The diagnosis of NAFLD was
      done according to established criteria. Receiver operating characteristics (ROC)
      curves were applied to detect areas under the ROC curves for each index. Nominal
      logistic regression analysis was used to estimate the odds ratio for risk factors
      of NAFLD. RESULTS: About 38.17% employees had NAFLD, more in men than in women.
      The prevalence of NAFLD increased with increasing age. In both genders, the
      prevalence of metabolic factors was higher in the NAFLD group. Body max index,
      waist circumference, weight-to-height ratio, blood pressure, blood glucose, total
      cholesterol, triglyceride, low density lipoprotein, high density lipoprotein and
      uric acid were found to have a diagnostic value for NAFLD. Body max index is a
      better index for diagnosing NAFLD. Uric acid is a new diagnosing index not
      inferior to lipid metabolic factors. Metabolic factors can increase the risk of
      NAFLD up to 1.5 ~ 3.8 times. CONCLUSIONS: Older age, male gender, metabolic
      factors such as obesity, abdominal obesity, dyslipidemia, hypertension or type 2
      diabetes are risk factors for NAFLD. Prevalence of NAFLD in Shanghai employees is
      high. Prevention is extremely important. Those achieve the critical point should
      have early intervention.

PMID- 22978802
TI  - Learning needs of patients with heart failure a descriptive, exploratory study.
AB  - AIMS AND OBJECTIVES: To assess the learning needs of patients with heart failure
      in Korea as this information is the cornerstone for developing a programme based
      on patients' learning needs. BACKGROUND: Heart failure is a life-threatening
      event and a significant cause of morbidity and mortality in Korea. Cardiac
      educational programmes are intended to prevent the recurrence of heart failure
      and improve patients' quality of life. However, patients' information requests
      have historically not been well met by physicians and nurses in Korea. DESIGN: A
      descriptive and exploratory study was designed. METHODS: We recruited 121
      patients with heart failure between the ages of 19-88 years. Self-report
      questionnaires, which included general characteristics, disease-related
      characteristics and the Heart Failure Patients' Learning Needs Inventory patient
      version, were used to gather data. RESULTS: The only general characteristic that
      was significantly related to patients' learning needs was their occupation. No
      disease-related characteristics were related to learning needs. The overall mean
      learning needs score was 3.78. CONCLUSION: Patients' learning needs in Korea are
      lower than those typically seen in Western countries. Korean patients with heart
      failure had a low level of knowledge about heart failure and did not recognise
      the importance of being informed about their disease, which is why Korean
      patients with heart failure tend to depend on their physicians to make decisions
      related to their health management. These conditions can negatively affect
      clinical outcomes. RELEVANCE TO CLINICAL PRACTICE: Although an educational
      programme for patients with heart failure should be based on the patients'
      learning needs, heart failure management and education programmes in Korea are
      not currently developed using a needs-based approach. Therefore, this study will
      provide a basis for encouraging Korean patients to obtain information about their
      disease and to guide professionals in developing heart failure management and
      education programmes.

PMID- 22978803
TI  - Lattice dynamics through the structural phase transition in D-amphetamine
      sulfate.
AB  - The polarized infrared and Raman spectra of the single-crystalline D-amphetamine
      sulfate have been measured as a function of temperature in the vicinity of the
      structural phase transition. Infrared and Raman-active modes are identified and
      assigned. Significant signatures of the structural phase transition are observed
      in the temperature dependence of infrared modes both of the D-amphetamine unit
      and the sulfate anion. The changes reflect differences in the unit cell between
      low- and high-temperature phases of the D-amphetamine sulfate. Temperature
      dependence of the vibrational mode parameters displays pronounced hysteresis
      between 333 and 338 K that is extended over a smaller temperature range than 325
      345 K found in the earlier DSC study.

PMID- 22978804
TI  - Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of
      patients with non small cell lung cancer.
AB  - BACKGROUND: Overexpression of the tumor suppressor gene p53 and the marker for
      cellular proliferation Ki67 in open lung biopsies are indicated as predictor
      factors of survival of patients with lung cancer. However, the prognostic value
      of p53 and Ki67 in fiberoptic bronchial biopsies (FBB) has not been fully
      investigated. We evaluated p53 and Ki67 immunostaining in FBB from 19 with Non
      Small-Cell Lung Cancer (NSCLC: 12 adenocarcinomas, 5 squamous cell carcinomas and
      2 NSCLC-NOS). METHODS: FBB specimens were fixed in formalin, embedded in
      paraffin, and immunostained using anti-p53 and anti-Ki67 antibodies. Slides were
      reviewed by two independent observers and classified as positive (+ve) when the
      number of cells with stained nuclei exceeded 15% for p53 or when >25% positive
      cells were observed throughout each section for Ki67. RESULTS: Positive (+ve)
      immunostaining was found in 9 patients for p53 (47.37%) and 8 patients for Ki67
      (42.10%). We examined overall survival curves of the patients with Mantel's
      logrank test, both p53 -ve and Ki67 -ve patients had significantly higher
      survival rates than p53 + ve (p < 0.005) and Ki67 + ve (p < 0,0001),
      respectively. CONCLUSION: This study suggests that negative immunostaining of
      fiberoptic bronchial biopsies for p53 and Ki67 could represent a better
      prognostic factor for patients with NSCLC.

PMID- 22978805
TI  - Efficacy and safety of valsartan in reducing blood pressure and albuminuria in
      Chinese patients with essential hypertension: a multicenter prospective open
      label observational study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 80 or 160 mg/day valsartan in
      Chinese adult patients with essential hypertension and albuminuria. METHODS: A
      multicenter prospective open-label observational study was conducted. Adult
      hypertensive patients with albuminuria were treated with 80 or 160 mg/day
      valsartan. Blood pressure (BP) was recorded at weeks 4, 8 and 12. Albuminuria was
      selectively measured at week 12. RESULTS: The intent-to-treat (ITT) population
      included 1180 patients. Mean sitting systolic BP (MSSBP) and diastolic BP (MSDBP)
      at baseline was 153.5 [14.41] (mean [SD]) and 88.2 [11.99] (mean [SD]) mmHg.
      MSSBP and MSDBP at week 4 (mean [SD]: 139.1 [12.02] and 82.2 [8.54] mmHg), week 8
      (mean [SD]: 135.3 [10.46] and 80.2 [7.55] mmHg) and week 12 (mean [SD]: 132.1
      [9.80] and 78.1 [6.88] mmHg) were significantly lower than baseline (p < 0.001).
      The BP control rate of ITT patients at week 12 was 17.8%. Diabetic patients
      exhibited lower BP control rate than non-diabetic patients (14.0 vs. 22.4%, p <
      0.001). A total of 904 patients had albuminuria assessed at week 12. UACR and
      UAER at week 12 were lower compared with baseline (p < 0.05). In all, 171
      patients (18.9%) returned to normal albuminuria and albuminuria normalization
      percentage in diabetic patients exceeded that of non-diabetic patients (26.3 vs.
      12.1%, p < 0.001). Albuminuria declined by more than 50% in 340 patients (37.6%)
      and more diabetic patients exhibited such decline in albuminuria than non
      diabetic patients (41.7 vs. 33.8%, p < 0.05). No serious drug-related adverse
      effects (AEs) were observed. LIMITATIONS: Prior antihypertensive treatment before
      valsartan administration may interfere with the efficacy of subsequent treatment.
      The discrepancy between 80 and 160 mg may affect patient outcomes and occurrence
      of AEs. CONCLUSIONS: Valsartan can safely and effectively reduce BP and
      albuminuria in Chinese adult patients with essential hypertension and
      albuminuria. Valsartan has the more dramatic effect on albuminuria in diabetic
      patients than non-diabetic patients.

PMID- 22978806
TI  - Benidipine persistently inhibits delayed rectifier K(+)-channel currents in
      murine thymocytes.
AB  - Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in
      their plasma membranes, and the channels play crucial roles in the lymphocyte
      activation and proliferation. Since 1,4-dihydropyridine (DHP) Ca(2+) channel
      blockers (CCBs), which are highly lipophilic, exert relatively stronger
      immunomodulatory effects than the other types of CCBs, they would affect the
      Kv1.3-channel currents in lymphocytes. In the present study, employing the
      standard patch-clamp whole-cell recording technique in murine thymocytes, we
      examined the effects of benidipine, one of the most lipophilic DHPs, on the
      channel currents and the membrane capacitance and compared them with those of
      nifedipine. Both drugs significantly suppressed the peak and the pulse-end
      currents of the channels with significant decreases in the membrane capacitance.
      However, the effects of benidipine were more marked than those of nifedipine and
      were irreversible after the drug withdrawal. This study demonstrated for the
      first time that DHP CCBs, such as nifedipine and benidipine, exert inhibitory
      effects on thymocyte Kv1.3-channel currents. The persistent effect of benidipine
      was thought to be associated with its sustained accumulation in the plasma
      membranes as detected by the long-lasting decrease in the membrane capacitance.

PMID- 22978807
TI  - Total synthesis of (+/-)-communesin F via a cycloaddition with indol-2-one.
AB  - A concise total synthesis of (+/-)-communesin F has been completed in 15 linear
      steps from 4-bromotryptophol in an overall yield of 6.7%. A key step features the
      cycloaddition of indol-2-one with 3-(2-azidoethyl)-4-bromoindole and facilitates
      the rapid construction of the lower aminal-containing tetracyclic core of the
      natural product.

PMID- 22978808
TI  - Identification of novel 2-((1-(benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3
      phenylpropan-2-yl)carbamoyl)benzoic acid analogues as BMP-2 stimulators.
AB  - The synthesis and SAR studies of 10 new chemical entities (NCEs) that have shown
      BMP-2 stimulation and osteoblast differentiation are reported. Among these, 2-((1
      (benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2
      yl)carbamoyl)benzoic acid (11) was the most effective while its analogue 13 also
      showed good activity in inducing osteoblast BMP-2 production. Compound 11 induced
      osteoblast differentiation in vitro, and this effect was abrogated by a
      physiological BMP-2 inhibitor, noggin. It also exhibited dose dependent increase
      in nascent bone formation (2.16- and 3.12-fold more than the control at 1 and 5
      mg/kg dose, respectively) at the fracture site in rats. At the maximum osteogenic
      concentration, compound 11 significantly inhibited osteoblastic proteosomal
      activity. This compound was safe, as it had no effect on BMP synthesis in
      cardiovascular tissue.

PMID- 22978809
TI  - Prolonged survival after sequential multimodal treatment in metastatic renal cell
      carcinoma: two case reports and a review of the literature.
AB  - INTRODUCTION: In this case series and short review of the literature, we
      underline the impact of nephrectomy combined with sequential therapy based on
      cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors
      along with metastasectomy on overall survival and quality of life in patients
      with metastatic clear cell renal carcinoma. CASE PRESENTATION: In the first of
      two cases reported here, a 53-year-old Caucasian man underwent a radical left
      nephrectomy for renal cell cancer and relapsed with a bone metastasis in his
      right humerus. He was treated with closed nailing and cytokine-based
      chemotherapy. For 5 years, the disease was stable and he had great improvement in
      quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and
      thorax soft tissue. He was then treated with antiangiogenic factors and mammalian
      target of rapamycin inhibitors. The disease progressed until September 2009, when
      he died of allergic shock during a blood transfusion, 9 years after the initial
      diagnosis of renal cell cancer.In the second case, a 54-year-old Caucasian man
      underwent a radical left nephrectomy for renal cell cancer. A year later, the
      disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was
      initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he
      underwent a metastasectomy. Nine months later, magnetic resonance imaging of his
      brain revealed a focal right occipitoparietal lesion, which was resected. After
      two years of active surveillance, the disease relapsed as a pulmonary metastasis
      and he was treated with an antiangiogenic factor. Further progressions presenting
      as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine
      bone metastases were sequentially observed. He then received a first-generation
      mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a
      second-generation mammalian target of rapamycin inhibitor and palliative
      radiotherapy. Ten years after the initial diagnosis of renal cell cancer, his
      disease is stable and he is on a third antiangiogenic factor and leads an active
      life. CONCLUSIONS: One multidisciplinary approach to patients with metastatic
      renal cell cancer combines nephrectomy, metastasectomy, and radiotherapy (when
      feasible) with medical therapy based on cytokines and targeted treatment
      employing agents inhibiting angiogenesis, other receptor tyrosine kinases, and
      mammalian target of rapamycin. This approach could prolong survival and improve
      quality of life.

PMID- 22978810
TI  - Anterior cervical discectomy and fusion: comparison of titanium and
      polyetheretherketone cages.
AB  - BACKGROUND: Titanium (TTN) cages have a higher modulus of elasticity when
      compared with polyetheretherketone (PEEK) cages. This suggests that TTN-cages
      could show more frequent cage subsidence after anterior cervical discectomy and
      fusion (ACDF) and therefore might lead to a higher loss of correction. We
      compared the long term results of stand-alone PEEK- and TTN-cages in a comparable
      patient collective that was operated under identical operative settings. METHODS:
      From 2002 to 2007 154 patients underwent single-level ACDF for degenerative disc
      disease (DDD). Clinical and radiological outcome were assessed in 86 eligible
      patients after a mean of 28.4 months. 44 patients received a TTN- and 42 patients
      a PEEK-cage. RESULTS: Solid arthrodesis was found in 93.2% of the TTN-group and
      88.1% of the PEEK-group. Cage subsidence was observed in 20.5% of the TTN- and
      14.3% of the PEEK-group. A significant segmental lordotic correction was achieved
      by both cage-types. Even though a loss of correction was found at the last follow
      up in both groups, it did not reach the level of statistical significance.
      Statistical analysis of these results revealed no differences between the TTN-
      and PEEK-group.When assessed with the neck disability index (NDI), the visual
      analogue scale (VAS) of neck and arm pain and Odom's criteria the clinical data
      showed no significant differences between the groups. CONCLUSIONS: Clinical and
      radiological outcomes of ACDF with TTN- or PEEK-cages do not appear to be
      influenced by the chosen synthetic graft. The modulus of elasticity represents
      only one of many physical properties of a cage. Design, shape, size, surface
      architecture of a cage as well as bone density, endplate preparation and applied
      distraction during surgery need to be considered as further important factors.

PMID- 22978811
TI  - Clinicopathological significance of laminin-5gamma2 chain expression in
      superficial esophageal cancer.
AB  - The glycoprotein laminin 5gamma2 chain (LN-5gamma2) has recently become a focus
      of increased interest and investigation as a marker of invasion in
      gastrointestinal malignancies. We investigated the significance of LN-5gamma2
      expression as a prognostic factor in superficial esophageal cancer. The study
      population consisted of 87 patients who had undergone a transthoracic
      esophagectomy and three-field lymphadenectomy for the treatment of superficial
      esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded
      sections of the resected specimens were examined using immunohistochemical
      staining and hematoxylin and eosin staining to assess the correlations between
      the LN-5gamma2 expression pattern and the clinicopathological factors (age, sex,
      T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative
      growth pattern, tumor node metastasis classification of malignant tumors [TNM]
      stage, etc.) and the patient outcome. The expression pattern of LN-5gamma2 was
      classified into an extracellular type (E type), characterized by the staining of
      extracellular matrix such as the basement membrane and the stroma (31 cases,
      35.6%), and a cytoplasmic type (C type), characterized by the staining of the
      cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not
      correlated with any of the clinicopathological factors that were assessed.
      However, univariate analyses of the survival analysis data showed that the N
      factor (P = 0.011), TNM stage (P = 0.011), and LN-5gamma2 C type (P = 0.017) were
      prognostic factors. A multivariate analysis revealed that the N-factor (P =
      0.049) and LN-5gamma2 C type (P = 0.048) were prognostic factors. In the survival
      analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor
      (P = 0.048), TNM stage (P = 0.048), and LN-5gamma2 C type (P = 0.029) were
      prognostic factors, while a multivariate analysis showed that the LN-5gamma2 C
      type (P = 0.035) was a prognostic factor. The C type expression of LN-5gamma2,
      i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among
      the patients with superficial esophageal cancer in the present series.
      Observation of the LN-5gamma2 expression pattern may be useful for the diagnosis
      of highly malignant tumors. 

PMID- 22978812
TI  - Aromatase expression in human peripheral blood leucocytes (PBLs) and in various
      tissues in primates: studies in elderly humans and cynomolgus monkeys.
AB  - BACKGROUND: Previous analysis of aromatase gene and protein expression in
      peripheral blood leucocytes (PBLs), studied in children and adults, was extended
      to elderly subjects. In addition, we assessed whether aromatase expression in
      PBLs could be used as a parameter of aromatase expression in other tissues, using
      the cynomolgus monkey as model. METHODS: Real-time PCR analysis of aromatase gene
      expression and protein evaluation by Western blot was performed in PBLs of human
      elderly subjects and in various tissues from cynomolgus monkeys. RESULTS: No
      gender-related difference in CYP19A1 mRNA and protein expression in PBLs from
      human elderly women and men was found. In elderly male cynomolgus monkeys,
      CYP19A1 mRNA and protein were expressed in all cells and tissues analysed, with
      the lowest levels in PBLs but no clear-cut correlation with other tissues.
      CONCLUSIONS: Aromatase expression in PBLs in elderly human subjects is not gender
      related and cannot be a surrogate of aromatase expression for other tissues.

PMID- 22978813
TI  - Pilot study of aromatic hydrocarbon adsorption characteristics of disposable
      filtering facepiece respirators that contain activated carbon.
AB  - Disposable filtering facepiece respirators (FFRs) used by health care workers are
      not designed to reduce the inhalation of volatile organic compounds (VOCs). Smoke
      generating surgical procedures release VOCs and have been associated with the
      following complaints: foul smell, headaches, nausea, irritated throat and lungs,
      and asthma. Organic vapor FFRs that contain activated carbon are used by
      industrial workers to provide odor relief. These respirators remove irritating
      odors but are not marketed as respirators that provide respiratory protection
      against a gas or vapor. This study investigated the aromatic hydrocarbon
      adsorption capabilities of nuisance organic vapor (OV) FFRs. Three OV FFR models
      were tested to determine the 10% breakthrough time of three aromatic hydrocarbons
      at ambient room temperature and relative humidity. All respirator models were
      exposed to each vapor separately in three duplicate tests (n = 27). The
      respirator was sealed with silicone to an AVON-ISI headform that was placed in a
      chamber and exposed to VOC-laden air (20 ppm, 37 L/min). Periodically, gas
      samples were directed to an SRI gas chromatograph (Model 8610C) for analysis. All
      respirators performed similarly. The average 10% breakthrough values for all
      tests were at least 64 min, 96 min, and 110 min for benzene, toluene, and xylene,
      respectively. Respirators were tested with challenge concentrations at nuisance
      levels (20 ppm) and did not exceed 10% breakthrough values for at least 61 min.
      While the results of this pilot study hold promise, there is a need for further
      investigation and validation to determine the effectiveness of nuisance FFRs in
      mitigating organic vapors such as benzene, toluene, and xylene.

PMID- 22978814
TI  - Evolution of blood pressure from adolescents to youth in salt sensitivies: a 18
      year follow-up study in Hanzhong children cohort.
AB  - BACKGROUND: Essential hypertension mostly originates from children. Salt
      Sensitivity (SS) is regarded as the intermediate phenotype of essential
      hypertension. The present study investigated the effects of salt-sensitivity on
      evolution of blood pressure (BP) and development to hypertension from adolescents
      to youth. METHODS: A baseline survey was carried out in 4,623 adolescents aged 6
      15 years old in Hanzhong rural areas in 1987, 310 of whom (mean 9.2 years) were
      randomly recruited for determination of salt sensitivity using the tests of oral
      saline load and furosemide sodium-volume depletion. SS was diagnosed in 101
      subjects while 209 were determined as non-salt-sensitive (NSS). We made a 18-year
      followed-up of the cohort in 2005. RESULTS: The response rate for surviving
      baseline adolescents was 71.9%. At follow up, BP in youth with baseline SS was
      higher than that in NSS (SBP:122.9 +/- 13.1 VS 117.3 +/- 12.4, P < 0.01; DBP:
      78.2 +/- 10.4 VS 74.7 +/- 10.8, P < 0.05). Longitudinal analysis of 18-year BP
      evolution, subjects in SS had greater Systolic BP change than subjects in
      NSS(19.6 +/- 12.714.7 +/- 12.2, P < 0.01). The incidence of hypertension in salt
      sensitive group was higher than that in NSS group (15.5% VS 6.3%, RR = 2.34, P <
      0.05). CONCLUSION: Our findings indicate that adolescents with higher BP salt
      sensitivity have a higher rate of incident hypertension in youth. Salt
      sensitivity could be at high risk predisposing to development of hypertension
      from adolescents to youth.

PMID- 22978815
TI  - Challenges in treating pediatric asthma in developing countries.
AB  - Asthma is the most common chronic disease in children in many low- and middle
      income countries. In these settings, the burden of childhood asthma is increasing
      and is associated with severe disease. There are a number of challenges to
      providing optimal management of childhood asthma in such settings. These include
      under-diagnosis of childhood asthma, access to care, ability of healthcare
      workers to manage asthma, availability and affordability of inhaled therapy,
      environmental control of potential triggers, education of healthcare providers
      and of the public, and cultural or language issues. International and national
      guidelines for childhood asthma have been produced, but implementation remains a
      real challenge. Access to and affordability of essential inhaled asthma drugs,
      especially low-dose inhaled corticosteroids and short-acting bronchodilators, are
      major challenges to effective asthma control in many countries. A low-cost spacer
      made from a plastic bottle is effective for use with a metered-dose inhaler, but
      use must be included in asthma educational initiatives. Educational programs for
      healthcare personnel and for the public that are culturally and language
      appropriate are needed for effective implementation of asthma guidelines.
      Socioeconomic and structural barriers to care within health services remain
      obstacles to achieving optimal treatment of asthma for many children.

PMID- 22978816
TI  - Detection of single influenza viral RNA in cells using a polymeric sequence
      probe.
AB  - A polynucleotide probe, call a polymeric sequence probe (PSP), was used to detect
      influenza A (Influenza A/WSN/33) NA (Neuraminidase) viral RNA in Madin-Darby
      canine kidney (MDCK) cells. The PSP is a single-stranded DNA molecule with ~2,000
      tandem repeat fluorescence binding sites and target binding sites that can bind
      with multiple fluorescence complementary oligos and target viral RNA using a
      fluorescence in situ hybridization (FISH) process. A single viral RNA labeled by
      PSP can be directly observed in MDCK cells. The simple FISH protocol enables the
      observation and quantitative analysis of the infectious process and drug effects
      with ultrahigh sensitivity and spatial resolution.

PMID- 22978817
TI  - Lithium amide (LiNH2) under pressure.
AB  - Static high pressure lithium amide (LiNH(2)) crystal structures are predicted
      using evolutionary structure search methodologies and intuitive approaches. In
      the process, we explore the relationship of the structure and properties of solid
      LiNH(2) to its molecular monomer and dimer, as well as its valence-isoelectronic
      crystalline phases of methane, water, and ammonia all under pressure. A NaNH(2)
      (Fddd) structure type is found to be competitive for the ground state of LiNH(2)
      above 6 GPa with the P = 1 atm I4[overline] phase. Three novel phases emerge at
      11 (P4[overline]2(1)m), 13 (P4(2)/ncm), and 46 GPa (P2(1)2(1)2(1)), still
      containing molecular amide anions, which begin to form N-H...N hydrogen bonds.
      The P2(1)2(1)2(1) phase remains stable over a wide pressure range. This phase and
      another Pmc2(1) structure found at 280 GPa have infinite ...(H)N...H...N(H)...H
      polymeric zigzag chains comprising symmetric N...H...N hydrogen bonds with one NH
      bond kept out of the chain, an interesting general feature found in many of our
      high pressure (>280 GPa) LiNH(2) structures, with analogies in high pressure
      H(2)O-ices. All the predicted low enthalpy LiNH(2) phases are calculated to be
      enthalpically stable with respect to their elements but resist metallization with
      increasing pressure up to several TPa. The possibility of Li sublattice melting
      in the intermediate pressure range structures is raised.

PMID- 22978818
TI  - Endoscopic treatment of ganglioneuroma of the colon associated with a lipoma: a
      case report.
AB  - INTRODUCTION: Ganglioneuromas are rare benign peripheral neuroblastic tumors
      characterized by hyperplasia of ganglion cells, nerve fibers, and supporting
      cells. They are not usually localized in the colon. CASE PRESENTATION: A 61-year
      old Caucasian man was admitted to our department for colon cancer screening. A
      colonoscopy revealed a lipoma of 5cm in diameter, two micropolyps of less than
      1cm, and one sessile polyp of 0.6cm in diameter. The polyps were removed with hot
      biopsy forceps. A histological examination revealed two hyperplastic polyps and
      one ganglioneuroma polyp. A follow-up colonoscopy showed no signs of recurrence
      after 16 months. CONCLUSIONS: Although a few cases of lipomas associated with
      ganglioneuromatous syndrome have been reported, the association of an intestinal
      lipoma with an isolated ganglioneuroma polyp has not been described. The
      implications of this association are unknown.

PMID- 22978819
TI  - Cerebral blood flow quantification in the rat: a direct comparison of arterial
      spin labeling MRI with radioactive microsphere PET.
AB  - BACKGROUND: Arterial spin labeling magnetic resonance imaging (ASL-MRI) has been
      recognised as a valuable method for non-invasive assessment of cerebral blood
      flow but validation studies regarding quantification accuracy by comparison
      against an accepted gold standard are scarce, especially in small animals. We
      have conducted the present study with the aim of comparing ASL flow-sensitive
      alternating inversion recovery (FAIR)-derived unidirectional water uptake (K1)
      and 68Ga/64Cu microsphere (MS)-derived blood flow (f) in the rat brain. METHODS:
      In 15 animals, K1and f were determined successively in dedicated small animal
      positron emission tomography and MR scanners. The Renkin-Crone model modified by
      a scaling factor was used for the quantification of f and K1. RESULTS: Below
      about 1 mL/min/mL, we obtain an approximately linear relationship between f and
      K1. At higher flow values, the limited permeability of water at the blood brain
      barrier becomes apparent. Within the accessed dynamic flow range (0.2 to 1.9
      mL/min/mL), the data are adequately described by the Renkin-Crone model yielding
      a permeability surface area product of (1.53+/-0.46) mL/min/mL. CONCLUSION: The
      ASL-FAIR technique is suitable for absolute blood flow quantification in the rat
      brain when using a one-compartment model including a suitable extraction
      correction for data evaluation. TRIAL REGISTRATION: 24-9168.21-4/2004-1
      (registered in Freistadt Sachsen, Landesdirektion Dresden).

PMID- 22978820
TI  - Risk stratification in Wolff-Parkinson-White syndrome: the correlation between
      noninvasive and invasive testing in pediatric patients.
AB  - BACKGROUND: In Wolff-Parkinson-White (WPW) syndrome, rapid antegrade conduction
      of atrial tachyarrhythmias can result in ventricular fibrillation and sudden
      death. Antegrade conduction can be assessed through noninvasive testing or
      invasive electrophysiology study (EPS). We aimed to determine the correlation
      between noninvasive testing and EPS in a pediatric WPW population. METHODS: All
      WPW patients <21 years who underwent EPS over a 10-year period were identified.
      Noninvasive testing reviewed included electrocardiogram, Holter, and exercise
      stress test (EST). Patients were classified as low-risk if preexcitation was lost
      during any test. EPS data reviewed included antegrade conduction during atrial
      pacing and atrial fibrillation. Conduction through the accessory pathway (AP) to
      a cycle length <= 250 ms was considered rapid, otherwise patients were nonrapid.
      Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of
      noninvasive testing to correctly identify nonrapid conduction was calculated.
      RESULTS: There were 135 EPS. Twenty-four patients (18%) were classified low-risk
      noninvasively. Two of the 24 (8%) had rapid conduction at baseline EPS. The
      sensitivity, specificity, PPV, and NPV of low-risk noninvasive testing to predict
      nonrapid conduction was 22%, 94%, 92%, and 31%, respectively. Sixteen of the 24
      had low-risk EST and none had rapid conduction at baseline EPS. The specificity
      and PPV of low-risk EST were 100%. CONCLUSION: Loss of preexcitation during
      noninvasive testing had high specificity and PPV for nonrapid antegrade
      conduction during baseline EPS. Abrupt loss of preexcitation during EST was a
      highly reliable noninvasive marker of nonrapid AP conduction at baseline in our
      pediatric WPW patients.

PMID- 22978821
TI  - Lifestyle factors and site-specific risk of hip fracture in community dwelling
      older women--a 13-year prospective population-based cohort study.
AB  - BACKGROUND: Several risk factors are associated to hip fractures. It seems that
      different hip fracture types have different etiologies. In this study, we
      evaluated the lifestyle-related risk factors for cervical and trochanteric hip
      fractures in older women over a 13-year follow-up period. METHODS: The study
      design was a prospective, population-based study consisting of 1681 women (mean
      age 72 years). Seventy-three percent (n = 1222) participated in the baseline
      measurements, including medical history, leisure-time physical activity, smoking,
      and nutrition, along with body anthropometrics and functional mobility. Cox
      regression was used to identify the independent predictors of cervical and
      trochanteric hip fractures. RESULTS: During the follow-up, 49 cervical and 31
      trochanteric fractures were recorded. The women with hip fractures were older,
      taller, and thinner than the women with no fractures (p < 0.05). Low functional
      mobility was an independent predictor of both cervical and trochanteric fractures
      (HR = 3.4, 95% CI 1.8-6.6, and HR = 5.3, 95% CI 2.5-11.4, respectively). Low
      baseline physical activity was associated with an increased risk of hip fracture,
      especially in the cervical region (HR = 2.5, 95% CI 1.3-4.9). A decrease in
      cervical fracture risk (p = 0.002) was observed with physically active
      individuals compared to their less active peers (categories: very low or low,
      moderate, and high). Moderate coffee consumption and hypertension decreased the
      risk of cervical fractures (HR = 0.4, 95% CI 0.2-0.8, for both), while smoking
      was a predisposing factor for trochanteric fractures (HR = 3.2, 95% CI 1.1-9.3).
      CONCLUSIONS: Impaired functional mobility, physical inactivity, and low body mass
      may increase the risk for hip fractures with different effects at the cervical
      and trochanteric levels.

PMID- 22978823
TI  - Evaluation of Masimo signal extraction technology pulse oximetry in anaesthetized
      pregnant sheep.
AB  - OBJECTIVE: Evaluation of the accuracy of Masimo signal extraction technology
      (SET) pulse oximetry in anaesthetized late gestational pregnant sheep. STUDY
      DESIGN: Prospective experimental study. ANIMALS: Seventeen pregnant Merino ewes.
      METHODS: Animals included in study were late gestation ewes undergoing general
      anaesthesia for Caesarean delivery or foetal surgery in a medical research
      laboratory. Masimo Radical-7 pulse oximetry (SpO(2) ) measurements were compared
      to co-oximetry (SaO(2) ) measurements from arterial blood gas analyses. The
      failure rate of the pulse oximeter was calculated. Accuracy was assessed by Bland
      & Altman's (2007) limits of agreement method. The effect of mean arterial blood
      pressure (MAP), perfusion index (PI) and haemoglobin (Hb) concentration on
      accuracy were assessed by regression analysis. RESULTS: Forty arterial blood
      samples paired with SpO(2) and blood pressure measurements were obtained. SpO(2)
      ranged from 42 to 99% and SaO(2) from 43.7 to 99.9%. MAP ranged from 24 to 82
      mmHg, PI from 0.1 to 1.56 and Hb concentration from 71 to 114 g L(-1) . Masimo
      pulse oximetry measurements tended to underestimate oxyhaemoglobin saturation
      compared to co-oximetry with a bias (mean difference) of -2% and precision
      (standard deviation of the differences) of 6%. Accuracy appeared to decrease when
      SpO(2) was <75%, however numbers were too small for statistical comparisons. Hb
      concentration and PI had no significant effect on accuracy, whereas MAP was
      negatively correlated with SpO(2) bias. CONCLUSIONS AND CLINICAL RELEVANCE:
      Masimo SET pulse oximetry can provide reliable and continuous monitoring of
      arterial oxyhaemoglobin saturation in anaesthetized pregnant sheep during
      clinically relevant levels of cardiopulmonary dysfunction. Further work is needed
      to assess pulse oximeter function during extreme hypotension and hypoxaemia.

PMID- 22978822
TI  - Innate immune responses to TLR2 and TLR4 agonists differ between baboons,
      chimpanzees and humans.
AB  - BACKGROUND: African catarrhine primates differ in bacterial disease
      susceptibility. METHODS: Human, chimpanzee, and baboon blood were stimulated with
      TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real
      time PCR. RESULTS: Humans and chimpanzees shared similar cytokine/chemokine
      responses, while baboon cytokine/chemokine induction differed. Generally,
      responses were agonist independent. CONCLUSIONS: These primates tend to generate
      species rather than agonist-specific responses to bacterial agonists.

PMID- 22978824
TI  - Multitarget-directed benzylideneindanone derivatives: anti-beta-amyloid (Abeta)
      aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B)
      inhibition properties against Alzheimer's disease.
AB  - A novel series of benzylideneindanone derivatives were designed, synthesized, and
      evaluated as multitarget-directed ligands against Alzheimer's disease. The in
      vitro studies showed that most of the molecules exhibited a significant ability
      to inhibit self-induced beta-amyloid (Abeta(1-42)) aggregation (10.5-80.1%, 20
      MUM) and MAO-B activity (IC(50) of 7.5-40.5 MUM), to act as potential
      antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In
      particular, compound 41 had the greatest ability to inhibit Abeta(1-42)
      aggregation (80.1%), and MAO-B (IC(50) = 7.5 MUM) was also an excellent
      antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)
      induced Abeta(1-42) aggregation and disassembling the well-structured Abeta
      fibrils. These results indicated that compound 41 is an excellent multifunctional
      agent for the treatment of AD.

PMID- 22978825
TI  - The pharmacokinetics of methadone in adolescents undergoing posterior spinal
      fusion.
AB  - BACKGROUND: The optimal methadone dosing regimen for children undergoing spinal
      surgery is uncertain because of sparse pediatric pharmacokinetic data and a
      paucity of analgesic effect data. The minimum effective analgesic concentration
      of methadone in opioid naive adults is 58 mcg . L(-1). METHODS: Adolescents aged
      12-19 years undergoing idiopathic scoliosis correction were administered 0.25 mg
      . kg(-1) racemic methadone IV prior to surgical incision. Arterial blood samples
      for methadone assay were obtained at 0 min, 5 min, 10 min, 15 min, 20 min, 40
      min, 1 h, 2 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, and 48 h. Compartment
      analysis was undertaken using nonlinear mixed effects models. Parameter estimates
      were standardized to a 70-kg person using allometric models. RESULTS: A three
      compartment linear disposition model best described observed time-concentration
      profiles. Population parameter estimates (between-subjects variability) were
      central volume (V1) 19.1 (126%) L 70 kg(-1), peripheral volumes of distribution
      V2 65.5 (60%) L 70 kg(-1), V3 485 (23%) L 70 kg(-1), clearance (CL) 9.3 (11%) L .
      h(-1) . 70 kg(-1), and inter-compartment clearances Q2 282 (95%) L . h(-1) 70 kg(
      1), Q3 139 (42%) L . h(-1) 70 kg(-1). The terminal elimination half-life was 44.4
      h. The mean observed methadone concentration was <58 mcg . L(-1) by the first
      hour after administration. CONCLUSIONS: Current pharmacokinetic parameter
      estimates in adolescents are similar to those reported in adults. Methadone
      undergoes rapid redistribution after bolus administration. This may result in
      plasma concentrations that provide inadequate analgesia postoperatively. We would
      suggest following the bolus (0.25 mg.kg(-1)) with an infusion (0.1-0.15 mg . kg(
      1) . h(-1) for 4 h) during spinal surgery to ensure adequate plasma
      concentrations for 24 h.

PMID- 22978826
TI  - Modified endoscopic submucosal dissection with enucleation for treatment of
      gastric subepithelial tumors originating from the muscularis propria layer.
AB  - BACKGROUND: Gastric subepithelial tumors are usually asymptomatic and observed
      incidentally during endoscopic examination. Although most of these tumors are
      considered benign, some have a potential for malignant transformation,
      particularly those originating from the muscularis propria layer. For this type
      of tumor, surgical resection is the standard treatment of choice. With recent
      advent of endoscopic resection techniques and devices, endoscopic submucosal
      dissection (ESD) has been considered as an alternative way of treatment. The aim
      of this study is to demonstrate the feasibility of a modified ESD technique with
      enucleation for removal of gastric subepithelial tumors originating from the
      muscularis propria layer, and to evaluate its efficacy and safety. METHODS: From
      November 2009 to May 2011, a total of 16 patients received a modified ESD with
      enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and
      originated from the muscularis propria layer of the stomach, as shown by
      endoscopic ultrasonography (EUS). The procedure was conducted with an insulated
      tip knife 2. Patient's demographics, tumor size and pathological diagnosis,
      procedure time, procedure-related complication, and treatment outcome were
      reviewed. RESULTS: Fifteen of the sixteen tumors were successful complete
      resection. The mean tumor size measured by EUS was 26.1 mm (range: 20-42 mm). The
      mean procedure time was 52  minutes (range: 30-120  minutes). Endoscopic features
      of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical
      diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients.
      There was no procedure-related perforation or overt bleeding. During a mean
      follow up duration of 14.8  months (range: 6-22  months), there was no tumor
      recurrence or metastasis. CONCLUSIONS: Using a modified ESD with enucleation for
      treatment of gastric subepithelial tumors originating from the muscularis propria
      layer and larger than 2 cm, complete resection can be successfully performed
      without serious complication. It is a safe and effective alternative to surgical
      therapy for these tumors of 2 to 5 cm in size.

PMID- 22978827
TI  - Lamellar structures of MUC2-rich mucin: a potential role in governing the barrier
      and lubricating functions of intestinal mucus.
AB  - Mucus is a ubiquitous feature of mammalian wet epithelial surfaces, where it
      lubricates and forms a selective barrier that excludes a range of particulates,
      including pathogens, while hosting a diverse commensal microflora. The major
      polymeric component of mucus is mucin, a large glycoprotein formed by several MUC
      gene products, with MUC2 expression dominating intestinal mucus. A satisfactory
      answer to the question of how these molecules build a dynamic structure capable
      of playing such a complex role has yet to be found, as recent reports of distinct
      layers of chemically identical mucin in the colon and anomalously rapid transport
      of nanoparticles through mucus have emphasized. Here we use atomic force
      microscopy (AFM) to image a MUC2-rich mucus fraction isolated from pig jejunum.
      In the freshly isolated mucin fraction, we find direct evidence for trigonally
      linked structures, and their assembly into lamellar networks with a distribution
      of pore sizes from 20 to 200 nm. The networks are two-dimensional, with little
      interaction between lamellae. The existence of persistent cross-links between
      individual mucin polypeptides is consistent with a non-self-interacting lamellar
      model for intestinal mucus structure, rather than a physically entangled polymer
      network. We only observe collapsed entangled structures in purified mucin that
      has been stored in nonphysiological conditions.

PMID- 22978828
TI  - Popcorn is more satiating than potato chips in normal-weight adults.
AB  - BACKGROUND: Strategies that may increase compliance to reduced energy intakes are
      needed to reduce the health burden of obesity. Conflicting evidence exists
      regarding the effects of snacking on satiety and energy intake. METHODS: This
      study compared short-term satiety from two common snack foods, low fat popcorn or
      potato chips. Using a counterbalanced within-subject design, 35 normal weight non
      smoking participants (17 men, 18 women) ages 20-50 years (mean age 33 +/- 11, BMI
      23 +/- 2 kg/m2) consumed four conditions each: 200 mL of water (control), one cup
      (4 g, 15 kcal) popcorn, 6 cups (27 g, 100 kcal) popcorn, and one cup (28 g, 150
      kcal) potato chips, each with 200 mL water. Participants rated their hunger,
      satisfaction, prospective consumption, and thirst on 100 mm visual analogue
      scales 30 minutes after commencement of snack consumption. In addition, post
      snack energy intake from an ad libitum meal (amount served less amount remaining)
      was measured, and the test food and meal combined energy intake and energy
      compensation were calculated. RESULTS: Participants expressed less hunger, more
      satisfaction, and lower estimates of prospective food consumption after six cups
      of popcorn compared to all other treatments (P < 0.05). Energy compensation was
      220% +/- 967%, 76% +/- 143% and 42% +/- 75% after one cup popcorn, six cups
      popcorn and one cup potato chips, respectively. Combined energy intake was
      significantly greater (P < 0.01) during the potato chips condition (803 +/- 277
      kcal) compared to control (716 +/- 279 kcal) or popcorn conditions (698 +/- 286
      kcal for one cup and 739 +/- 294 kcal for six cups). Combined energy intakes from
      both popcorn conditions were not significantly different than control (p > 0.05).
      CONCLUSION: Popcorn exerted a stronger effect on short-term satiety than did
      potato chips as measured by subjective ratings and energy intake at a subsequent
      meal. This, combined with its relatively low calorie load, suggests that whole
      grain popcorn is a prudent choice for those wanting to reduce feelings of hunger
      while managing energy intake and ultimately, body weight.

PMID- 22978829
TI  - E-selectin deficiency attenuates brain ischemia in mice.
AB  - AIMS: To determine whether E-selectin deficiency can attenuate brain ischemia in
      a mouse model of focal cerebral ischemia. METHODS: E-selectin was determined in
      spontaneously hypertensive rats (SHRs) and stroke-prone spontaneously
      hypertensive rats (SHR-SPs). E-selectin knockout (Es(-/-) ) mice and wild-type
      control (WT) mice underwent permanent distal middle cerebral artery occlusion
      (MCAO). Behavioral analyses were performed followed by the measurement of infarct
      areas. Myeloperoxidase (MPO) protein was determined by Western blot. IL-6, IL
      1beta, and TNF-alpha were detected by ELISA. In situ detection of apoptotic cells
      was performed by TUNEL staining. RESULTS: The brain and serum E-selectin levels
      were higher in SHR-SPs than in SHRs (P < 0.05) after salt intake. E-selectin
      deficiency improved neurological function and reduced infarct area in cerebral
      ischemic mice. MPO and IL-1beta were lower in Es(-/-)  mice than in WT mice. In
      addition, the number of apoptotic cells in Es(-/-)  mice was significantly less
      than in WT mice after MCAO. CONCLUSIONS: E-selectin deficiency presents
      protective effect on cerebral ischemia. This protective effect is likely achieved
      by the inhibition of inflammation and apoptosis.

PMID- 22978830
TI  - Replacement of the ascending aorta for severe atherosclerosis during coronary
      artery bypass surgery.
AB  - BACKGROUND AND AIM: In the present study, we investigated the benefit of
      ascending aorta replacement in patients with severe aortic atherosclerosis who
      undergo coronary artery bypass surgery (CABG). METHODS: From January 2001 to
      April 2011, 3842 patients underwent CABG and in 36 of these patients (31 male, 5
      female) the ascending aorta was replaced due to severe atherosclerosis. Total
      circulatory arrest was used in 22 patients (61%). The patients were followed for
      69 +/- 36 months (1-133 months) and compared to a control group of patients. The
      control group consisted of patients who underwent CABG with or without a
      concomitant procedure (n = 3806). RESULTS: For the study group, the mean additive
      and logistic Euroscores of the patients were nine and 20, respectively. One
      stroke (2.8%) was observed and this patient died in the early postoperative
      period. There were a total of four confirmed deaths (12%) at any time point over
      the length of the follow-up among the patients who were discharged from the
      hospital. Two of them died of malignancy (lung and gastric tumors) and the other
      two from cardiac reasons. No patients had a stroke during follow-up. For the
      control group the mean age was 61 +/- 1, the stroke rate was 0.6%, and the
      mortality rate was 0.96%, and the mean logistic and additive Euroscores were 3.7
      +/- 4.4, and 3.5 +/- 2.5, respectively. CONCLUSIONS: Replacement of highly
      calcified ascending aortas during CABG can be safely performed in selected
      patients with good long-term outcomes.

PMID- 22978831
TI  - A simple technique for securing Gore-Tex neochordal height and knot slippage in
      mitral valve repair.
AB  - Polytetrafluoroethylene or Gore-Tex sutures are used for chordal replacement, and
      are durable but extremely slippery, a property which causes knot slippage and
      ineffective neochordal length. We report a modification that is simple and
      reproducible in preventing knot slippage and maintaining optimal neochordal
      length, without the use of devices or additional sutures.

PMID- 22978832
TI  - A massive post-sternotomy sternal defect treated by allograft sternal
      transplantation.
AB  - We report a case of a patient with complete sternal destruction after cardiac
      surgery, who underwent total sternal replacement with sternal allograft, titanium
      bars, and screws.

PMID- 22978833
TI  - Mitral valve re-repair in an adolescent patient with prosthetic ring
      endocarditis: posterior leaflet augmentation and posterior strip annuloplasty.
AB  - Endocarditis after mitral valve (MV) annuloplasty is uncommon. The ring used in
      MV annuloplasty is often inadequate because it opposes the growth of the MV
      leaflets and annulus. We report a 15-year-old male that required redo surgery for
      prosthetic ring endocarditis 40 months after a previous MV annuloplasty. After
      the previous ring was removed, the undergrown posterior leaflet was repaired with
      pericardial augmentation and the posterior annulus was stabilized with a Mitra
      Lift(r) supra-annular strip to preserve a flexible valve orifice and allow the
      anterior MV annulus and the commissures to grow in relation to body size.

PMID- 22978834
TI  - Surgical management of coronary artery disease associated with malignancy.
AB  - Surgical management of patients with combined coronary artery disease and
      malignancy remains a challenge. In this review the time of surgical intervention,
      whether to treat the malignancy or the coronary artery disease first, and which
      bypass technique should be used during myocardial revascularization are reviewed
      to determine the most optimal strategy to manage patients who require coronary
      surgical revascularization and present with an underlying malignancy.

PMID- 22978835
TI  - Treatment of delirium following cardiac surgery.
AB  - Postoperative delirium is a common medical complication following cardiac
      surgery. This paper will outline the treatment options for delirium with a focus
      on prophylactic use of risperidone before cardiac surgery.

PMID- 22978836
TI  - Allogenic blood transfusion in cardiac surgery.
AB  - Blood transfusion carries benefits and risks. Adult cardiac surgery accounts for
      a significant proportion of all red blood cells transfusions. However, the
      identification of the patient, who will truly benefit from transfusions, is still
      controversial. This review provides an overview on allogenic blood transfusions
      in adult cardiac surgery.

PMID- 22978837
TI  - Optimization of Impella 5.0 implantation using mini-sternotomy approach in
      postmyocardial infarction cardiogenic shock.
AB  - The Impella Recover LP 5.0(r) (Abiomed, Inc. Danvers, MA, USA) is an aortic
      transvalvular microaxial pump designed to unload the left ventricle and to ensure
      a systemic flow in severe left ventricular dysfunction. Surgical implantation
      using femoral or right subclavian approach may be difficult in certain
      circumstances, such as encountered in peripheral vascular disease, patients with
      small vessels or during substantial use of vasoactive drugs responsible for
      vasospasm. We propose a simple and effective technique for implantation of the
      Impella 5.0 LVAD by means of a mini-sternotomy in patients with postinfarction
      refractory cardiogenic shock.

PMID- 22978838
TI  - Aberrant left subclavian artery associated with a Kommerell's diverticulum and a
      left-sided aortic arch.
AB  - Kommerell's diverticulum is most commonly associated with either an aberrant left
      subclavian artery from a right-sided aortic arch or an aberrant right subclavian
      artery from a left-sided aortic arch. We describe an exceedingly rare case of an
      aberrant left subclavian artery arising from a Kommerell's diverticulum in a
      patient with a left-sided aortic arch, the "nonaberrant aberrant left subclavian
      artery."

PMID- 22978839
TI  - Sinus of Valsalva aneurysm with left anterior descending coronary aneurysm.

PMID- 22978840
TI  - The influence of deep hypothermic global brain ischemia on EEG in a new rat
      model.
AB  - OBJECTIVES: Neurological complications following deep hypothermic circulatory
      arrest (DHCA) occur between t 4% ~ 25%. However, the cerebral injury mechanisms
      are still not well understood due to a lack of a practical and simple animal
      model. We aimed to establish a rodent deep hypothermic global brain ischemia
      (DHGBI) model, which can be used to elucidate these mechanisms in future studies.
      DESIGN: 30 Sprague-Dawley rats were divided randomly into three groups: the
      carotid occlusion DHGBI group, the internal carotid shunt DHGBI group, and the
      sham operation group. We validated the model in terms of electroencephalogram
      (EEG) and regional cerebral blood flow (rCBF). All rats were sacrificed for
      analysis of brain moisture capacity after 24 hours. RESULTS: In the internal
      carotid shunt DHGBI group the EEG activity was suppressed to "flat-line" and the
      relative power of the alpha and theta frequency bands was decreased (p < 0.05).
      However, in the carotid occlusion DHGBI group we only observed the relative power
      of the alpha frequency band depressed (p < 0.05). The rCBF was significantly
      decreased in all groups. In the internal carotid shunt DHGBI group the rCBF was
      significantly reduced to 4.27 +/- 2.75%, and was lower than the other two groups
      (p < 0.05). The result of brain moisture capacity was consistent with the EEG and
      rCBF observations. CONCLUSIONS: The current study presents a novel cerebral
      recovery model of DHCA in the rat. This experimental model may be suitable to
      further elucidate the mechanisms associated with adverse cerebral outcomes after
      DHCA and to investigate potential neuroprotective strategies.

PMID- 22978841
TI  - Isolated right superior vena cava draining into the left atrium.
AB  - A 10-year-old male was admitted to our institution with complaints of mild
      cyanosis and dyspnea. Transthoracic echocardiography and angiography revealed a
      right superior vena cava (SVC) draining into the left atrium. At the time of
      surgery, the right SVC was connected to the right atrium.

PMID- 22978842
TI  - Repair of a distal ductal origin of the left pulmonary artery associated with a
      ventricular septal defect.
AB  - Absence of the main branch of the pulmonary artery (PA) with an intracardiac
      defect is commonly associated with conotruncal cardiac anomaly. It is rarely
      associated with a ventricular septal defect and PA hypertension. We describe a
      surgical technique to implant an aberrant left PA to the main PA in a case of a
      ventricular septal defect, severe pulmonary hypertension, and distal ductal
      origin of the left PA.

PMID- 22978844
TI  - Elective noncardiac surgery in patients with left ventricular assist devices.
AB  - As the number of heart failure patients supported with left ventricular assist
      devices (LVAD) increases, the frequency of elective, noncardiac surgery in this
      patient population will similarly rise. We retrospectively analyzed our LVAD
      patient database and identified six patients who underwent elective, noncardiac
      surgery while on LVAD support. These cases are discussed, with an emphasis on the
      anesthetic and perioperative considerations. These patients have an acceptable
      risk profile for elective surgery and should be treated similarly to their age
      matched counterparts not on LVAD support.

PMID- 22978843
TI  - The spectrum of complications following left ventricular assist device placement.
AB  - INTRODUCTION: Left ventricular assist device (LVAD) support is associated with
      many complications, but relatively few studies have examined the full spectrum of
      complications beyond infectious and bleeding events. METHODS: We conducted a
      retrospective review of patients receiving either a pulsatile-flow Heartmate XVE
      (HM1; Thoratec Corp., Pleasanton, CA, USA) or continuous-flow Heartmate II (HM2;
      Thoratec Corp.) LVAD at our institution (June 2000 to March 2012). Frequency and
      date of onset of nonbleeding, noninfectious complications were examined. RESULTS:
      One hundred eighty-two LVADs were implanted, 49 HM1, and 133 HM2. Support
      duration was longer for HM2s (median 358 vs. 112 days; p = 0.0003). Overall, the
      most frequent complications were respiratory failure, ventricular arrhythmia,
      atrial arrhythmia, right heart failure, and renal failure. Respiratory failure,
      arrhythmias, severe psychiatric events, and renal failure all occurred with
      median date of onset <= seven days postprocedure. Right heart failure, hepatic
      failure, thromboembolism, and transient ischemic attacks had a median date of
      onset 8 to 30 days postprocedure. Stroke, hemolysis, and device failure occurred
      mostly more than a month postoperatively. Right heart failure, hepatic failure,
      and device failure were more frequent in HM1 patients than in HM2 patients.
      Several events, including stroke, had much later onset in HM2 patients.
      CONCLUSION: In this 10-year review of complications following LVAD implantation,
      the most common adverse events tended to occur early after implantation. As
      pulsatile-flow HM1s showed greater frequency and earlier onset of some adverse
      events, our data suggest better overall outcomes with the continuous-flow HM2s.

PMID- 22978845
TI  - HeartMate-II left ventricular assist device infections resulting from
      gastrointestinal-tract fistulas.
AB  - BACKGROUND: In patients with a left ventricular assist device (LVAD), pump
      related infection can cause adverse effects that may result in death. METHODS: We
      describe three patients who had infections related to a fistula between the
      gastrointestinal (GI) tract and the LVAD pocket and who subsequently underwent
      successful heart transplantation without developing sepsis. In no case did the
      LVAD-related infection adversely affect the outcome of transplantation.
      CONCLUSIONS: For detecting the fistulas, full upper-GI endoscopy and colonoscopy
      were superior to other types of diagnostic imaging studies.

PMID- 22978846
TI  - Response to 'Plasma proteins present in osteoarthritic synovial fluid can
      stimulate cytokine production via Toll-like receptor 4'.

PMID- 22978847
TI  - Prospective evaluation of defibrillation threshold and postshock rhythm in young
      ICD recipients.
AB  - BACKGROUND: Adaptation of implantable cardioverter defibrillator (ICD) systems to
      the needs of pediatric and congenital heart patients is problematic due to
      constraints of vascular and thoracic anatomy. An improved understanding of the
      defibrillation energy and postshock pacing requirements in such patients may help
      direct more tailored ICD therapy. We describe the first prospective evaluation of
      defibrillation threshold (DFT) and postshock rhythm in this population. METHODS:
      We prospectively studied patients <= 60 kg at time of ICD intervention. DFTs were
      obtained using a binary search protocol with three VF inductions. Postshock
      pacing was programmed using a stepwise protocol, lowering the rate prior to each
      VF induction. RESULTS: Twenty patients were enrolled: 11 had channelopathy, five
      congenital heart disease, and four cardiomyopathy. The median age was 16 years,
      median weight 48 kg. Twelve patients had a transvenous high-voltage coil; eight
      had pericardial +/- subcutaneous coil(s). Median DFT was 7 J (range 3-31 J);
      19/20 patients had DFT <= 15 J and all patients <25 kg had DFT <= 9 J (n = 6).
      There was no difference in DFT between patients with transvenous versus
      pericardial +/- subcutaneous coils (median 7 J vs 6 J, P = 0.59). No patient with
      normal atrioventricular conduction prior to defibrillation required postshock
      pacing (n = 16). There were no adverse events. CONCLUSIONS: These data suggest
      that many pediatric ICD patients have low DFTs and adequate postshock escape
      rhythm. This may help determine appropriate parameters for future design of
      pediatric-specific ICDs.

PMID- 22978848
TI  - Prescription and dosing of urate-lowering therapy, rather than patient
      behaviours, are the key modifiable factors associated with targeting serum urate
      in gout.
AB  - BACKGROUND: Long term serum urate (SU) lowering to a target of <0.36 mmol/l (6
      mg/dl) is recommended for effective gout management. However, many studies have
      reported low achievement of SU targets. The aim of this cross-sectional study was
      to examine the clinical and psychological factors associated with SU targets in
      patients with gout. METHODS: Patients with gout for <10 years were recruited from
      primary and secondary care settings. SU target was defined as SU concentration
      <0.36 mmol/L at the time of the study visit. Both clinical and psychological
      factors associated with SU target were analysed. The relationship between SU
      target and measures of gout activity such as flare frequency, tophi, work
      absences, and Health Assessment Questionnaire-II was also analysed. RESULTS: Of
      the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36
      mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target
      (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose,
      patient confidence to keep SU under control, female sex, and ethnicity were
      independently associated with SU target. Other patient psychological measures and
      health-related behaviours, including adherence scores, were not independently
      associated with SU target in those taking ULT. Creatinine clearance, diuretic
      use, age, and body mass index were not associated with SU target. Patients at SU
      target reported lower gout flare frequency, compared with those not at target (p
      = 0.03). CONCLUSIONS: ULT prescription and dosing are key modifiable factors
      associated with achieving SU target. These data support interventions focusing on
      improved use of ULT to optimise outcomes in patients with gout.

PMID- 22978850
TI  - Early adjuvant use of nonopioids associated with reduced odds of serious
      postoperative opioid adverse events and need for rescue in children.
AB  - OBJECTIVES: Examine factors associated with opioid adverse drug events (ADE) in
      children. SPECIFIC AIMS: Examine whether adjuvant nonopioid use is associated
      with a decreased probability of opioid-ADEs and need for rescue. BACKGROUND:
      Opioid-ADEs contribute to serious preventable harm for hospitalized children.
      Adjuvant nonopioid use may mitigate opioid risk postoperatively, yet few studies
      support this notion. METHOD: This nested case-control study included children who
      required intervention or rescue from opioid-ADEs and procedure-matched controls.
      Data were recorded from medical records and primary outcomes included serious
      opioid-ADEs (over-sedation and respiratory depression) and need for rescue (e.g.,
      naloxone, rapid response team). Hierarchical logistic regression (HLR) models
      examined relationships between factors and opioid-ADEs. Early clinical signs and
      symptoms of deterioration were examined. RESULTS: Twenty five children with
      opioid-ADEs and 98 children without events were included. ASA-PS remained an
      independent risk factor (odds ratio, 2.56 [1.09, 6.03]; P = 0.031), while
      adjuvant nonopioids a risk reduction factor for opioid-ADEs (OR, 0.16 [0.05,
      0.47]; P = 0.001) and need for rescue (0.14 [0.04, 0.47]; P = 0.001).
      Supplemental oxygen use at PACU discharge was associated with an increased odds
      of opioid-ADEs (OR, 3.72 [1.35, 10.23]; P = 0.007) and need for rescue (5.5 [1.7,
      17.82]; P = 0.002). CONCLUSIONS: Findings from this study suggest that strategies
      such as early use of adjuvant nonopioids may reduce risk of opioid-ADEs
      postoperatively. Furthermore, children who require supplemental oxygen early
      postoperatively may be at heightened risk of later events.

PMID- 22978849
TI  - Molecular mechanisms of acquired proteasome inhibitor resistance.
AB  - The development of proteasome inhibitors (PIs) has transformed the treatment of
      multiple myeloma and mantle cell lymphoma. To date, two PIs have been FDA
      approved, the boronate peptide bortezomib and, most recently, the epoxyketone
      peptide carfilzomib. However, intrinsic and acquired resistance to PIs, for which
      the underlying mechanisms are poorly understood, may limit their efficacy. In
      this Perspective, we discuss recent advances in the molecular understanding of PI
      resistance through acquired bortezomib resistance in human cell lines and evolved
      salinosporamide A (marizomib) resistance in bacteria. Resistance mechanisms
      discussed include the up-regulation of proteasome subunits and mutations of the
      catalytic beta-subunits. Additionally, we explore potential strategies to
      overcome PI resistance.

PMID- 22978851
TI  - Combining time of flight and diffraction tomography for high resolution breast
      imaging: initial in vivo results (L).
AB  - Ultrasound tomography (UST) is being developed to address the limitations of
      mammography in breast cancer detection. Central to the success of UST is the
      possibility of obtaining high-resolution images of tissue mechanical properties
      across the whole breast. A recent paper [Huthwaite and Simonetti, J. Acoust. Soc.
      Am. 130, 1721-1734 (2011)] made use of a numerical phantom to demonstrate that
      sufficient image resolution can be obtained by simply treating refraction and
      diffraction effects in consecutive steps through the combination of ray-based
      time of flight and diffraction tomography. This letter presents the first
      experimental demonstration of the method using phantom and invivo data from a
      cancer patient.

PMID- 22978852
TI  - Architectural shape and early acoustic efficiency in concert halls (L).
AB  - Supplying sufficient early reflections to audience members is an important
      prerequisite to good acoustic quality in performing arts spaces. However, the
      relationship between the geometry of a room and its acoustic efficiency in terms
      of early energy has rarely been investigated using basic geometrical principles.
      The present study demonstrates the possibility of predicting the average value of
      early reflected energy across the audience area using solid angles. The formulas
      obtained display the influence of various factors on average early energy; in
      particular, the direction of arrival of early reflections is found to play a
      significant role, which highlights interesting implications for the acoustic
      design of concert halls.

PMID- 22978853
TI  - A Bayesian inference model for speech localization (L).
AB  - The localization of active speakers with microphone arrays is an active research
      line with a considerable interest in many acoustic areas. Many algorithms for
      source localization are based on the computation of the Generalized Cross
      Correlation function between microphone pairs employing phase transform
      weighting. Unfortunately, the performance of these methods is severely reduced
      when wall reflections and multiple sound sources are present in the acoustic
      environment. As a result, estimating the number of active sound sources and their
      actual directions becomes a challenging task. To effectively tackle this problem,
      a Bayesian inference framework is proposed. Based on a nested sampling algorithm,
      a mixture model and its parameters are estimated, indicating both the number of
      sources-model selection-and their angle of arrival-parameter estimation,
      respectively. A set of measured data demonstrates the accuracy of the proposed
      model.

PMID- 22978854
TI  - Generalized method of moments: a boundary integral framework for adaptive
      analysis of acoustic scattering.
AB  - Boundary integral equations (BIEs) find applications in problems ranging from
      sonar to medical diagnostics. The two ingredients of the BIE solution technique
      are (1) representation of the domain and (2) design of approximation spaces to
      represent physical quantities on the domain. These, in concert, affect accuracy
      and convergence of the simulation. This paper presents a framework that permits
      the development of a scheme for refinement (of size and order) in both geometry
      and function representations. Further, this permits flexibility in the types of
      basis functions that can be used. Capabilities of the proposed framework are
      shown via a number of numerical examples.

PMID- 22978855
TI  - A first-order k-space model for elastic wave propagation in heterogeneous media.
AB  - A pseudospectral model of linear elastic wave propagation is described based on
      the first order stress-velocity equations of elastodynamics. k-space adjustments
      to the spectral gradient calculations are derived from the dyadic Green's
      function solution to the second-order elastic wave equation and used to (a)
      ensure the solution is exact for homogeneous wave propagation for timesteps of
      arbitrarily large size, and (b) also allows larger time steps without loss of
      accuracy in heterogeneous media. The formulation in k-space allows the wavefield
      to be split easily into compressional and shear parts. A perfectly matched layer
      (PML) absorbing boundary condition was developed to effectively impose a
      radiation condition on the wavefield. The staggered grid, which is essential for
      accurate simulations, is described, along with other practical details of the
      implementation. The model is verified through comparison with exact solutions for
      canonical examples and further examples are given to show the efficiency of the
      method for practical problems. The efficiency of the model is by virtue of the
      reduced point-per-wavelength requirement, the use of the fast Fourier transform
      (FFT) to calculate the gradients in k space, and larger time steps made possible
      by the k-space adjustments.

PMID- 22978856
TI  - Acoustoelastic Lamb wave propagation in biaxially stressed plates.
AB  - Acoustoelasticity, or the change in elastic wave speeds with stress, is a well
      studied phenomenon for bulk waves. The effect of stress on Lamb waves is not as
      well understood, although it is clear that anisotropic stresses will produce
      anisotropy in the Lamb wave dispersion curves. Here the theory of acoustoelastic
      Lamb wave propagation is developed for isotropic media subjected to a biaxial,
      homogeneous stress field. It is shown that, as expected, dispersion curves change
      anisotropically for most stresses, modes, and frequencies. Interestingly, for
      some mode-frequency combinations, changes in phase velocity are isotropic even
      for a biaxial stress field. Theoretical predictions are compared to experimental
      results for several Lamb wave modes and frequencies for uniaxial loads applied to
      an aluminum plate, and the agreement is reasonably good.

PMID- 22978857
TI  - An exact frequency-domain solution of the sound radiated from the rotating dipole
      point source.
AB  - An exact solution of the acoustic field around the rotating dipole source has
      been derived by using a series expansion method and the gradient calculation in
      the spherical and cylindrical coordinate systems which extends a previously
      published solution for a rotating monopole source. The proposed exact solution
      establishes an analytical method to predict the sound radiated from the rotating
      blades once the acoustic sources have been known.

PMID- 22978858
TI  - Consistent modeling of boundaries in acoustic finite-difference time-domain
      simulations.
AB  - The finite-difference time-domain method is one of the most popular for wave
      propagation in the time domain. One of its advantages is the use of a structured
      staggered grid, which makes it simple and efficient on modern computer
      architectures. A drawback, however, is the difficulty in approximating oblique
      boundaries, having to resort to staircase approximations. In many scattering
      problems this means that the grid resolution required to obtain an accurate
      solution is much higher than what is dictated by propagation in a homogeneous
      material. In this paper zero boundary data are considered, first for the velocity
      and then the pressure. These two forms of boundary conditions model perfectly
      rigid and pressure-release boundaries, respectively. A simple and efficient
      method to consistently model curved rigid boundaries in two dimensions was
      developed in Tornberg and Engquist [J. Comput. Phys. 227, 6922-6943 (2008)]. Here
      this treatment is generalized to three dimensions. Based on the approach of this
      method, a technique to model pressure-release surfaces with second order accuracy
      and without additional restriction on the timestep is also introduced. The
      structure of the standard method is preserved, making it easy to use in existing
      solvers. The effectiveness is demonstrated in several numerical tests.

PMID- 22978859
TI  - Parabolic equation modeling of high frequency acoustic transmission with an
      evolving sea surface.
AB  - The present paper examines the temporal evolution of acoustic fields by modeling
      forward propagation subject to sea surface dynamics with time scales of less than
      a second to tens of seconds. A time-evolving rough sea surface model is combined
      with a rough surface formulation of a parabolic equation model for predicting
      time-varying acoustic fields. Surface waves are generated from surface wave
      spectra, and stepped in time using a Runge-Kutta integration technique applied to
      linear evolution equations. This evolving, range-dependent surface information is
      combined with other environmental parameters and input to the acoustic model,
      giving an approximation of the time-varying acoustic field. The wide-angle
      parabolic equation model manages the rough sea surfaces by molding them into the
      boundary conditions for calculations of the near-surface acoustic field. This
      merged acoustic model is validated using concurrently-collected acoustic and
      environmental information, including surface wave spectra. Data to model
      comparisons demonstrate that the model is able to approximate the ensemble
      averaged acoustic intensity at ranges of about a kilometer for acoustic signals
      of around 15 kHz. Furthermore, the model is shown to capture variations due to
      surface fluctuations occurring over time scales of less than a second to tens of
      seconds.

PMID- 22978861
TI  - Application of the distributed point source method to rough surface scattering
      and ultrasonic wall thickness measurement.
AB  - The distributed point source method is commonly used to predict the complex
      acoustic field emitted by ultrasonic transducers. In this paper, it is presented
      as an alternative to conventional approaches often used when solving rough
      surface scattering problems. Surface shadowing and multiple scattering effects
      are inherently included in the mesh-free semi-analytical simulation method
      through matrix manipulation making it very efficient and simple to implement.
      Results are presented which illustrate the improvement in accuracy gained over
      the Kirchhoff approximation and the decrease in computational load over the
      finite element method, culminating in greater than an order of magnitude decrease
      in required simulation time. The method is applied to the practical problem of
      online wall thickness monitoring within corrosive environments, illustrating the
      variability in reflected pulse shape that could be expected from rough surfaces
      with similar statistics. Three commonly implemented time-of-flight algorithms are
      used to analyze a large number of simulated signals from which it is concluded
      that those based on first arrival time are more stable under increasing roughness
      conditions than those which are based on reflected pulse shape.

PMID- 22978860
TI  - Cross-imaging system comparison of backscatter coefficient estimates from a
      tissue-mimicking material.
AB  - A key step toward implementing quantitative ultrasound techniques in a clinical
      setting is demonstrating that parameters such as the ultrasonic backscatter
      coefficient (BSC) can be accurately estimated independent of the clinical imaging
      system used. In previous studies, agreement in BSC estimates for well
      characterized phantoms was demonstrated across different laboratory systems. The
      goal of this study was to compare the BSC estimates of a tissue mimicking sample
      measured using four clinical scanners, each providing RF echo data in the 1-15
      MHz frequency range. The sample was previously described and characterized with
      single-element transducer systems. Using a reference phantom for analysis,
      excellent quantitative agreement was observed across the four array-based imaging
      systems for BSC estimates. Additionally, the estimates from data acquired with
      the clinical systems agreed with theoretical predictions and with estimates from
      laboratory measurements using single-element transducers.

PMID- 22978862
TI  - Surface waves on a half space with depth-dependent properties.
AB  - The dispersive properties of surface waves on an isotropic elastic body with
      elastic moduli and mass density that depend on depth have been analyzed in the
      high frequency range, for the case of axially symmetric surface waves, which are
      of interest for point loading of a body. The method of approach requires some
      simplifications, but the final analysis yields simple expressions for the
      displacements, for the case that the two elastic moduli and the mass density each
      have different dependencies on depth. In a high-frequency approximation
      expressions are obtained for the displacements and the stresses. The condition
      that the surface tractions vanish at the free surface yields the dispersion
      equation which relates the surface wave velocity to the wavenumber. Conditions
      have been derived for a class of examples for which this equation yields a real
      valued surface wave velocity, and the displacement amplitudes decay exponentially
      with depth. Results for the surface wave velocity as a function of the wavenumber
      have been compared with numerical results which were obtained when the continuous
      inhomogeneity with depth is replaced by an equivalent layering. For some typical
      cases of increasing and decreasing material properties with depth, excellent
      agreement has been obtained between analytical and numerical results.

PMID- 22978863
TI  - Models of cylindrical bubble pulsation.
AB  - Three models are considered for describing the dynamics of a pulsating
      cylindrical bubble. A linear solution is derived for a cylindrical bubble in an
      infinite compressible liquid. The solution accounts for losses due to viscosity,
      heat conduction, and acoustic radiation. It reveals that radiation is the
      dominant loss mechanism, and that it is 22 times greater than for a spherical
      bubble of the same radius. The predicted resonance frequency provides a basis of
      comparison for limiting forms of other models. The second model considered is a
      commonly used equation in Rayleigh-Plesset form that requires an incompressible
      liquid to be finite in extent in order for bubble pulsation to occur. The radial
      extent of the liquid becomes a fitting parameter, and it is found that
      considerably different values of the parameter are required for modeling inertial
      motion versus acoustical oscillations. The third model was developed by V. K.
      Kedrinskii [Hydrodynamics of Explosion (Springer, New York, 2005), pp. 23-26] in
      the form of the Gilmore equation for compressible liquids of infinite extent.
      While the correct resonance frequency and loss factor are not recovered from this
      model in the linear approximation, it provides reasonable agreement with
      observations of inertial motion.

PMID- 22978864
TI  - The simulation of Lamb waves in a cracked plate using the scaled boundary finite
      element method.
AB  - The scaled boundary finite element method is applied to the simulation of Lamb
      waves for ultrasonic testing applications. With this method, the general
      elastodynamic problem is solved, while only the boundary of the domain under
      consideration has to be discretized. The reflection of the fundamental Lamb wave
      modes from cracks of different geometry in a steel plate is modeled. A test
      problem is compared with commercial finite element software, showing the
      efficiency and convergence of the scaled boundary finite element method. A
      special formulation of this method is utilized to calculate dispersion relations
      for plate structures. For the discretization of the boundary, higher-order
      elements are employed to improve the efficiency of the simulations. The
      simplicity of mesh generation of a cracked plate for a scaled boundary finite
      element analysis is illustrated.

PMID- 22978865
TI  - Ultrasonic resonant modes of piezoelectric balloons under internal pressure.
AB  - Properties of a piezoelectric polymeric angioplasty balloon that may decrease the
      problems of acute closure and restenosis are evaluated in this study.
      Polyvinylidene difluoride (PVDF), a piezoelectric and pyroelectric polymer, has
      sufficient strength to serve as a standard angioplasty balloon as well as
      functioning as an ultrasonic transmitter and/or receiver. These properties enable
      potential therapeutic applications using ultrasound such as plaque ablation and
      sonotherapy as well as vulnerable plaque diagnosis using thermography. This study
      investigates the resonant structure of the PVDF balloon catheter in the frequency
      range 5-100 kHz. Vibrations of the piezoelectric balloon are modeled using
      cylindrical shell theory and compared with the observed modal frequencies of PVDF
      cylinders with and without internal pressure. Modal frequencies are determined by
      measuring the near-field pressure response of the PVDF cylinders using a high
      frequency microphone. A rich nodal structure is observed between 5 and 100 kHz
      with peak relative amplitudes measured between 42 and 45 kHz. Higher order modes
      for cylinders with 9 MUm and 28 MUm wall thickness increase in frequency as the
      internal pressure is increased. Experimental measurements confirm theoretical
      models that predict both pressure-dependent and pressure-independent resonant
      frequencies. Frequencies of pressure-dependent modes are calculated within 2.2%
      of measured values at high pressure.

PMID- 22978866
TI  - Theoretical and experimental analysis of the stop-band behavior of elastic
      springs with periodically discontinuous of curvature.
AB  - The advanced design of springs with tailored transmission characteristics is
      proposed. The existence of frequency stop-bands in the transmission
      characteristics is theoretically predicted and experimentally validated. The
      underlying mechanism of generating stop-band behavior is the periodic
      discontinuity of the curvature. The theoretical analysis is performed in the
      framework of the Floquet theory for an infinitely long spring. Experimental
      results are obtained for the springs consisting of a small number of repeated
      periodicity cells.

PMID- 22978867
TI  - Broadband measurement of translational and angular vibrations using a single
      continuously scanning laser Doppler vibrometer.
AB  - A continuous scanning laser Doppler velocimetry (CSLDV) technique is used to
      measure the low frequency broadband vibrations associated with human skeletal
      muscle vibrations (typically f < 100 Hz) by continuously varying the orientation
      of laser beam over distances that are short compared to the characteristic
      wavelengths of the vibrations. The high frequency scan (compared to the vibration
      frequency) enables the detection of broadband translational and angular
      velocities at a single point using amplitude demodulation of the CSDLV signal.
      For instance, linear scans allow measurement of the normal surface velocity and
      one component of angular velocity vector, while circular scans allow measurement
      of an additional angular velocity component. This CSLDV technique is first
      validated here using gel samples mimicking soft tissues and then applied to
      measure multiple degrees of freedom (DOF) of a subject's hand exhibiting fatigue
      induced tremor. Hence this CSLDV technique potentially provides a means for
      measuring multiple DOF of small human body parts (e.g., fingers, tendons, small
      muscles) for various applications (e.g., haptic technology, remote surgery) when
      the use of skin-mounted sensors (e.g. accelerometers) can be problematic due to
      mass-loading artifacts or tethering issues.

PMID- 22978868
TI  - Noise suppression of a dipole source by tensioned membrane with side-branch
      cavities.
AB  - Reducing the ducted-fan noise at the low frequency range remains a big technical
      challenge. This study presents a passive approach to directly suppress the dipole
      sound radiation from an axial-flow fan housed by a tensioned membrane with cavity
      backing. The method aims at achieving control of low frequency noise with an
      appreciable bandwidth. The use of the membrane not only eliminates the
      aerodynamic loss of flow, but also provides flexibility in controlling the range
      of the stopband with high insertion loss by varying its tension and mass. A three
      dimensional model is presented which allows the performance of the proposed
      device to be explored analytically. With the proper design, this device can
      achieve a noise reduction of 5 dB higher than the empty expansion cavity recently
      proposed by Huang et al. [J. Acoust. Soc. Am. 128, 152-163 (2010)]. Through the
      detailed modal analysis, even in vacuo modes of the membrane vibration are found
      to play an important role in the suppression of sound radiation from the dipole
      source. Experimental validation is conducted with a loudspeaker as the dipole
      source and good agreement between the predicted and measured insertion loss is
      achieved.

PMID- 22978869
TI  - Traffic noise and blood pressure in low-socioeconomic status, African-American
      urban schoolchildren.
AB  - The primary aim of this field study was to investigate the relationships among
      residential noise exposure at home and at school and blood pressure in low
      socioeconomic status African-American children. Children were recruited from Boys
      and Girls Clubs in a mid-sized, Northeastern city. The sample consisted of 250
      schoolchildren (128 boys and 122 girls) aged 6-14 years. Each child was
      interviewed prior to anthropometric and blood pressure measurement. An
      oscillometric monitor was used for measurement of resting blood pressure.
      Correlation analysis in the overall sample showed no significant relationship
      between noise exposure and children's blood pressure. No interactions were found
      between noise at home and at schools as well as orientation of bedroom and/or
      living room and noise at home with blood pressure. A sub-sample of children was
      also examined by adding the orientation of bedroom and living room as inclusion
      criteria (n = 128), and there was an interaction between noise exposure and age
      on systolic blood pressure. In younger children aged 6-10 years, a significant
      positive relation was found between noise levels at homes and systolic blood
      pressure, controlling for body mass index (B = 0.48, 95% C.I. = 0.07 -0.88, p =
      0.02).

PMID- 22978870
TI  - Listening level of music through headphones in train car noise environments.
AB  - Although portable music devices are useful for passing time on trains, exposure
      to music using headphones for long periods carries the risk of damaging hearing
      acuity. The aim of this study is to examine the listening level of music through
      headphones in the noisy environment of a train car. Eight subjects adjusted the
      volume to an optimum level (L(music)) in a simulated noisy train car environment.
      In Experiment I, the effects of noise level (L(train)) and type of train noise
      (rolling, squealing, impact, and resonance) were examined. Spectral and temporal
      characteristics were found to be different according to the train noise type. In
      Experiment II, the effects of L(train) and type of music (five vocal and five
      instrumental music) were examined. Each music type had a different pitch strength
      and spectral centroid, and each was evaluated by phi(1) and W(phi(0)),
      respectively. These were classified as factors of the autocorrelation function
      (ACF) of the music. Results showed that L(music) increased as L(train) increased
      in both experiments, while the type of music greatly influenced L(music). The
      type of train noise, however, only slightly influenced L(music). L(music) can be
      estimated using L(train) and the ACF factors phi(1) and W(phi(0)).

PMID- 22978871
TI  - Measurement of reverberation gain in an urban environment.
AB  - Multipath propagation within an urban area introduces a specific type of
      reverberation in response to sound excitation. That appearance affects the level
      of ambient noise produced by strong sound sources. In this paper, the signals
      recorded during the 1999 bombing of Belgrade were used to analyze the
      characteristics of reverberation in that urban environment. Six recorded signals
      were selected among more than 50 explosions recorded at that time. Due to the
      impulse nature of sound sources, the recorded signals represent the impulse
      responses of that area. The measured reverberation time T30 is about 7 +/- 1 s in
      octaves between 31.5 Hz and 1 kHz. There is a variation of decay slope in time
      that is verified by differences between values of T10 and T30. The reverberation
      gain calculated from recorded signals is 2-7 dB, depending on the global position
      of the sound excitation point as well as its micro-location according to its
      position among the surrounding buildings. A variation of gain over octave bands
      is in the interval of approximately 3 dB. Information about reverberation gain in
      urban environment can be useful in a quick estimation of noise level produced by
      strong sound sources in a large area of urban environment.

PMID- 22978872
TI  - Thresholds for the slope ratio in determining transition time and quantifying
      diffuser performance in situ.
AB  - This study is concerned with an objective measure called the slope ratio that can
      detect acoustic defects due to unexpected pressure increases such as strong
      reflections and coincidental constructive interference. The slope ratio is the
      ratio of the instantaneous slope to the mean slope in a decay curve. The slope
      ratio was suggested for determining the room acoustic transition time
      experimentally, but its threshold criteria have not been thoroughly investigated.
      The thresholds for the slope ratio, particularly for applications such as
      determining the room acoustic transition time and quantifying in situ
      diffuseness, are examined for various room impulse responses. For the tested
      rooms, a slope ratio threshold of 11 gives the most consistent and systematic
      results.

PMID- 22978873
TI  - Numerical and analytical solutions for sound propagation and absorption in porous
      media at high sound pressure levels.
AB  - On the basis of the work of Wilson et al. [J. Acoust. Soc. Am. 84, 350-359
      (1988)], a more exact numerical approach was constructed for predicting the
      nonlinear sound propagation and absorption properties of rigid porous media at
      high sound pressure levels. The numerical solution was validated by the
      experimental results for sintered fibrous porous steel samples and its
      predictions were compared with the numerical solution of Wilson et al. An
      approximate analytical solution was further put forward for the normalized
      surface acoustic admittance of rigid air-saturated porous materials with infinite
      thickness, based on the wave perturbation method developed by Lambert and
      McIntosh [J. Acoust. Soc. Am. 88, 1950-1959 (1990)]. Comparisons were made with
      the numerical results.

PMID- 22978874
TI  - Energy- and wave-based beam-tracing prediction of room-acoustical parameters
      using different boundary conditions.
AB  - A beam-tracing model was used to study the acoustical responses of three empty,
      rectangular rooms with different boundary conditions. The model is wave-based
      (accounting for sound phase) and can be applied to rooms with extended-reaction
      surfaces that are made of multiple layers of solid, fluid, or poroelastic
      materials-the acoustical properties of these surfaces are calculated using Biot
      theory. Three room-acoustical parameters were studied in various room
      configurations: sound strength, reverberation time, and RApid Speech Transmission
      Index. The main objective was to investigate the effects of modeling surfaces as
      either local or extended reaction on predicted values of these three parameters.
      Moreover, the significance of modeling interference effects was investigated,
      including the study of sound phase-change on surface reflection. Modeling
      surfaces as of local or extended reaction was found to be significant for
      surfaces consisting of multiple layers, specifically when one of the layers is
      air. For multilayers of solid materials with an air-cavity, this was most
      significant around their mass-air-mass resonance frequencies. Accounting for
      interference effects made significant changes in the predicted values of all
      parameters. Modeling phase change on reflection, on the other hand, was found to
      be relatively much less significant.

PMID- 22978875
TI  - Rigid sphere room impulse response simulation: algorithm and applications.
AB  - Simulated room impulse responses have been proven to be both useful and
      indispensable for comprehensive testing of acoustic signal processing algorithms
      while controlling parameters such as the reverberation time, room dimensions, and
      source-array distance. In this work, a method is proposed for simulating the room
      impulse responses between a sound source and the microphones positioned on a
      spherical array. The method takes into account specular reflections of the source
      by employing the well-known image method, and scattering from the rigid sphere by
      employing spherical harmonic decomposition. Pseudocode for the proposed method is
      provided, taking into account various optimizations to reduce the computational
      complexity. The magnitude and phase errors that result from the finite order
      spherical harmonic decomposition are analyzed and general guidelines for the
      order selection are provided. Three examples are presented: an analysis of a
      diffuse reverberant sound field, a study of binaural cues in the presence of
      reverberation, and an illustration of the algorithm's use as a mouth simulator.

PMID- 22978876
TI  - Objective performance analysis of spherical microphone arrays for speech
      enhancement in rooms.
AB  - Reverberation and noise have a significant effect on the intelligibility of
      speech in rooms. The detection of clear speech in highly reverberant and noisy
      enclosures is an extremely difficult task. Recently, spherical microphone arrays
      have been studied for processing of sound fields in three-dimensions, with
      applications ranging from acoustic analysis to speech enhancement. This paper
      presents the derivation of a model that facilitates the prediction of spherical
      array configurations that guarantee an acceptable level of speech intelligibility
      in reverberant and noisy environments. A spherical microphone array is employed
      to generate a spatial filter that maximizes speech intelligibility according to
      an objective measure that combines the effects of both reverberation and noise.
      The spherical array beamformer is designed to enhance the speech signal while
      minimizing noise power and maintaining robustness over a wide frequency range.
      The paper includes simulation and experimental studies with a comparison to
      speech transmission index based analysis to provide initial validation of the
      model. Examples are presented in which the minimum number of microphones in a
      spherical array can be determined from environment conditions such as
      reverberation time, noise level, and distance of the array to the speech source.

PMID- 22978877
TI  - The forced sound transmission of finite single leaf walls using a variational
      technique.
AB  - The single wall is the simplest element of concern in building acoustics, but
      there still remain some open questions regarding the sound insulation of this
      simple case. The two main reasons for this are the effects on the excitation and
      sound radiation of the wall when it has a finite size, and the fact that the wave
      field in the wall is consisting of two types of waves, namely forced waves due to
      the exciting acoustic field, and free bending waves due to reflections in the
      boundary. The aim of the present paper is to derive simple analytical formulas
      for the forced part of the airborne sound insulation of a single homogeneous wall
      of finite size, using a variational technique based on the integral-differential
      equation of the fluid loaded wall. The so derived formulas are valid in the
      entire audible frequency range. The results are compared with full numerical
      calculations, measurements and alternative theory, with reasonable agreement.

PMID- 22978878
TI  - Input impedance in flow ducts: theory and measurement.
AB  - This paper presents both a theoretical and an experimental investigation of the
      influence of the mean flow on the input impedance of a duct. The input impedance
      of an axisymetrical flow duct is calculated, taking into account the convective
      effect of a uniform flow, the dissipative effect of a turbulent flow and the
      radiation in an open jet. Each of these effects is separately studied. An
      experimental apparatus has been specifically designed to lower flow noise on the
      transducers, taking advantage of the Two-Microphone-Three-Calibration (TMTC)
      method [V. Gibiat and F. Laloe, J. Acoust. Soc. Am. 88, 2533-2545 (1990)], whose
      full calibration process allows any geometry for the measurement head. Theory and
      experiments are compared for a 1 m long cylindrical duct carrying a flow whose
      Mach number equals up to 0.15. The resonant frequencies are in close agreement,
      within 3%. The relative evolution of the magnitude maxima with increasing flow
      are in good agreement, within 10%. Despite similar tendencies when modifying the
      mean flow velocity, the amplitude of variation of the magnitude is 2 to 5 times
      smaller in the experiments.

PMID- 22978879
TI  - Receiver operating characteristic for a spectrogram correlator-based humpback
      whale detector-classifier.
AB  - This paper presents recent experimental results and a discussion of system
      enhancements made to the real-time autonomous humpback whale detector-classifier
      algorithm first presented by Abbot et al. [J. Acoust. Soc. Am. 127, 2894-2903
      (2010)]. In February 2010, a second-generation system was deployed in an
      experiment conducted off of leeward Kauai during which 26 h of humpback
      vocalizations were recorded via sonobuoy and processed in real time. These data
      have been analyzed along with 40 h of humpbacks-absent data collected from the
      same location during July-August 2009. The extensive whales-absent data set in
      particular has enabled the quantification of system false alarm rates and the
      measurement of receiver operating characteristic curves. The performance impact
      of three enhancements incorporated into the second-generation system are
      discussed, including (1) a method to eliminate redundancy in the kernel library,
      (2) increased use of contextual analysis, and (3) the augmentation of the
      training data with more recent humpback vocalizations. It will be shown that the
      performance of the real-time system was improved to yield a probability of
      correct classification of 0.93 and a probability of false alarm of 0.004 over the
      66 h of independent test data.

PMID- 22978880
TI  - Robust acoustic source localization based on modal beamforming and time-frequency
      processing using circular microphone arrays.
AB  - Uniform circular array processing has been shown to be a very useful tool for
      broadband acoustic source localization over 360 degrees . Specifically,
      beamforming methods based on circular harmonics have attracted a lot of research
      attention in the last several years, as modal array signal processing is a very
      active research topic. On the other hand, due to the sparsity properties of
      speech, source localization methods in the time-frequency (T-F) domain have also
      demonstrated their capability to locate several simultaneous sources with high
      accuracy. In this paper, a localization framework based on circular harmonics
      beamforming and T-F processing that provides accurate localization performance
      under very adverse acoustic conditions is presented. Modal processing and
      sparsity-based localization are jointly addressed to estimate the direction-of
      arrival of multiple concurrent speech sources. Experiments in real and simulated
      environments with different microphone setups are discussed, showing the validity
      of the proposed approach and comparing its performance with other state-of-the
      art methods.

PMID- 22978881
TI  - Near-field acoustic holography using sparse regularization and compressive
      sampling principles.
AB  - Regularization of the inverse problem is a complex issue when using near-field
      acoustic holography (NAH) techniques to identify the vibrating sources. This
      paper shows that, for convex homogeneous plates with arbitrary boundary
      conditions, alternative regularization schemes can be developed based on the
      sparsity of the normal velocity of the plate in a well-designed basis, i.e., the
      possibility to approximate it as a weighted sum of few elementary basis
      functions. In particular, these techniques can handle discontinuities of the
      velocity field at the boundaries, which can be problematic with standard
      techniques. This comes at the cost of a higher computational complexity to solve
      the associated optimization problem, though it remains easily tractable with out
      of-the-box software. Furthermore, this sparsity framework allows us to take
      advantage of the concept of compressive sampling; under some conditions on the
      sampling process (here, the design of a random array, which can be numerically
      and experimentally validated), it is possible to reconstruct the sparse signals
      with significantly less measurements (i.e., microphones) than classically
      required. After introducing the different concepts, this paper presents numerical
      and experimental results of NAH with two plate geometries, and compares the
      advantages and limitations of these sparsity-based techniques over standard
      Tikhonov regularization.

PMID- 22978882
TI  - A frequency-selective feedback model of auditory efferent suppression and its
      implications for the recognition of speech in noise.
AB  - The potential contribution of the peripheral auditory efferent system to our
      understanding of speech in a background of competing noise was studied using a
      computer model of the auditory periphery and assessed using an automatic speech
      recognition system. A previous study had shown that a fixed efferent attenuation
      applied to all channels of a multi-channel model could improve the recognition of
      connected digit triplets in noise [G. J. Brown, R. T. Ferry, and R. Meddis, J.
      Acoust. Soc. Am. 127, 943-954 (2010)]. In the current study an anatomically
      justified feedback loop was used to automatically regulate separate attenuation
      values for each auditory channel. This arrangement resulted in a further
      enhancement of speech recognition over fixed-attenuation conditions. Comparisons
      between multi-talker babble and pink noise interference conditions suggest that
      the benefit originates from the model's ability to modify the amount of
      suppression in each channel separately according to the spectral shape of the
      interfering sounds.

PMID- 22978883
TI  - Frequency difference limens at high frequencies: evidence for a transition from a
      temporal to a place code.
AB  - It is commonly believed that difference limens for frequency (DLFs) for pure
      tones depend on a temporal mechanism (phase locking) for frequencies up to 4-5
      kHz and a place mechanism at higher frequencies. The DLFs predicted from a place
      mechanism, expressed as a proportion of center frequency (Deltaf/f), should be
      approximately invariant with frequency at medium to high frequencies. If there is
      a transition from a temporal to a place mechanism, Deltaf/f should increase with
      increasing center frequency until the transition occurs, and then reach a
      plateau. Published data do not show such an effect. In this study, DLFs were
      measured for center frequencies from 2 to 14 kHz, using earphones designed to
      produce a flat response at the eardrum. The level of every tone was varied over a
      range of +/-4 dB, to reduce loudness cues. The value of Deltaf/f increased
      progressively from 2 to 8 kHz, but did not change significantly for frequencies
      from 8 to 14 kHz. The results are consistent with the idea that there is a
      transition from a temporal to a place mechanism at about 8 kHz, rather than at 4
      5 kHz, as is commonly assumed.

PMID- 22978884
TI  - Pitch shifts on mistuned harmonics in the presence and absence of corresponding
      in-tune components.
AB  - Mistuning a harmonic produces an exaggerated change in its pitch, a component
      pitch shift. The origin of these pitch shifts was explored by manipulations
      intended to alter the grouping status of a mistuned target component in a
      periodic complex tone. In experiment 1, which used diotic presentation,
      reinstating the corresponding harmonic (in-tune counterpart) caused the pitch
      shifts on the mistuned target largely to disappear for components 3 and 4,
      although they remained for component 2. A computational model of component-pitch
      shifts, based on harmonic cancellation, was unable to explain the near-complete
      loss of pitch shifts when the counterpart was present; only small changes
      occurred. In experiment 2, the complex tone and mistuned component 4 were
      presented in the left ear and the in-tune counterpart was presented in the right.
      The in-tune counterpart again reduced component-pitch shifts, but they were
      restored when a captor complex into which the counterpart fitted as harmonic 3
      was added in the right ear; presumably by providing an alternative grouping
      possibility for the counterpart. It is proposed that component-pitch shifts occur
      only if the mistuned component is selected to contribute to the complex-tone
      percept; these shifts are eliminated if it is displaced by a better candidate.

PMID- 22978885
TI  - The role of envelope statistics in detecting changes in interaural correlation.
AB  - The role of envelope statistics in binaural masking-level differences (BMLDs) and
      correlation change detection was investigated in normal-hearing listeners.
      Thresholds and just-noticeable differences (JNDs) were measured for different
      bandwidths and center frequencies (500, 2000, 4000, and 8000 Hz) using Gaussian
      noises (GNs) and low-fluctuation noises (LFNs). At a 500-Hz center frequency, GN
      NoSo thresholds were higher than, NoSpi thresholds were lower than, and
      correlation change detection JNDs were the same as LFN thresholds and JNDs. At
      higher center frequencies, GN NoSpi thresholds were the same or higher than LFN
      thresholds and GN correlation change detection JNDs were much smaller than LFN
      JNDs. Using a pulsed sine vocoder, a second experiment was performed to
      investigate if binaural adaptation might contribute to the difference in GN and
      LFN detection. There was no effect of pulse rate, thus providing no clear
      evidence that binaural adaptation plays a role in these tasks. Both a cross
      correlation model and a model that utilized the fluctuations in the interaural
      differences could explain a majority of the variance in the LFN correlation
      change JNDs.

PMID- 22978886
TI  - Onset- and offset-specific effects in interaural level difference discrimination.
AB  - The relative sensitivity of human listeners to interaural level differences
      (ILDs) carried by the onsets, offsets, and interior portions of brief sounds was
      examined. Stimuli consisted of single 4000-Hz Gabor clicks (Gaussian-windowed
      tone bursts) or trains of 16 such clicks repeating at an interclick interval
      (ICI) of 2 or 5 ms. In separate conditions, ILDs favored the right ear by a
      constant amount for all clicks (condition RRRR) or a changing amount that was
      maximal at sound onset (condition R000), offset (condition 000R), both onset and
      offset (condition R00R), or at the temporal midpoint of the stimulus (condition
      0RR0). ILD increases and decreases were implemented as linear decibel sweeps
      across four clicks to minimize transient distortion. Threshold ILDs were
      determined adaptively for each of these conditions and for single clicks.
      Thresholds were similar for ILDs presented near sound onset or offset (condition
      R000 vs 000R) but lower when ILDs were carried by both onset and offset clicks
      (condition R00R) than for ILDs carried by interior clicks alone (condition 0RR0).
      The results suggest that similar sensitivity to onset and offset ILD does not
      reflect uniform temporal weighting; instead, ILD sensitivity favors onsets and
      offsets over the interior portions of sounds.

PMID- 22978887
TI  - Effects of reverberation and masker fluctuations on binaural unmasking of speech.
AB  - In daily life, listeners use two ears to understand speech in situations which
      typically include reverberation and non-stationary noise. In headphone
      experiments, the binaural benefit for speech in noise is often expressed as the
      difference in speech reception threshold between diotic (N(0)S(0)) and dichotic
      (N(0)S(pi)) conditions. This binaural advantage (BA), arising from the use of
      inter-aural phase differences, is about 5-6 dB in stationary noise, but may be
      lower in everyday conditions. In the current study, BA was measured in various
      combinations of noise and artificially created diotic reverberation, for normal
      hearing and hearing-impaired listeners. Speech-intelligibility models were
      applied to quantify the combined effects. Results showed that in stationary
      noise, diotic reverberation did not affect BA. BA was reduced in conditions where
      the masker fluctuated. With additional reverberation, however, it was restored.
      Results for both normal-hearing and hearing-impaired listeners were accounted for
      by assuming that binaural unmasking is only effectively realized at low
      instantaneous speech-to-noise ratios (SNRs). The observed BA was related to the
      distribution of SNRs resulting from fluctuations, reverberation, and peripheral
      processing. It appears that masker fluctuations and reverberation, both relevant
      for everyday communication, interact in their effects on binaural unmasking and
      need to be considered together.

PMID- 22978888
TI  - The effect of compression speed on intelligibility: simulated hearing-aid
      processing with and without original temporal fine structure information.
AB  - Hearing aids use amplitude compression to compensate for the effects of loudness
      recruitment. The compression speed that gives the best speech intelligibility
      varies among individuals. Moore [(2008). Trends Amplif. 12, 300-315] suggested
      that an individual's sensitivity to temporal fine structure (TFS) information may
      affect which compression speed gives most benefit. This hypothesis was tested
      using normal-hearing listeners with a simulated hearing loss. Sentences in a
      competing talker background were processed using multi-channel fast or slow
      compression followed by a simulation of threshold elevation and loudness
      recruitment. Signals were either tone vocoded with 1-ERB(N)-wide channels (where
      ERB(N) is the bandwidth of normal auditory filters) to remove the original TFS
      information, or not processed further. In a second experiment, signals were
      vocoded with either 1 - or 2-ERB(N)-wide channels, to test whether the available
      spectral detail affects the optimal compression speed. Intelligibility was
      significantly better for fast than slow compression regardless of vocoder channel
      bandwidth. The results suggest that the availability of original TFS or detailed
      spectral information does not affect the optimal compression speed. This
      conclusion is tentative, since while the vocoder processing removed the original
      TFS information, listeners may have used the altered TFS in the vocoded signals.

PMID- 22978890
TI  - Production of single and geminate stops in Japanese three- and four-mora words.
AB  - This study examined the durational structure of single and geminate stop
      distinction produced in three- and four-mora words of Japanese,
      (C(1))V(1)(C(2))C(2)V(2)X [(C(2))C(2) = the contrasting consonants; X = a CV
      mora, the moraic nasal, or a long vowel as part of V(2)]. The questions addressed
      were how factors such as speaking rate, segmental variability, and moraic
      composition of words affected the stop quantity distinction in words longer than
      well-studied disyllabic words, and whether there exists an invariant parameter
      that classified these two stop categories. Results showed that all of those
      factors systematically affected the duration of the contrasting stop closure, the
      unit of [(C(1))V(1)(C(2))C(2)V(2)], and the entire three- and four-mora words.
      However, the durational units of moras and words were well-structured, and the
      ratio of the contrasting stop closure to the [(C(1))V(1)(C(2))C(2)V(2)] unit, as
      well as the ratio of the closure to the entire word, were found to be invariant
      in indicating the stop quantity distinction. These results support the theory of
      relational acoustic invariance [Pickett et al., Phonetica 56, 135-157 (1999)] on
      the part of production. Furthermore, the results provide insight into different
      versions of Japanese mora hypothesis [Han, The Study of Sounds 10, 65-80 (1962);
      Port et al., J. Acoust. Soc. Am. 81(5), 1574-1585 (1987)], which have been under
      debate for five decades.

PMID- 22978889
TI  - Computational modeling of phonatory dynamics in a tubular three-dimensional model
      of the human larynx.
AB  - Simulation of the phonatory flow-structure interaction has been conducted in a
      three-dimensional, tubular shaped laryngeal model that has been designed with a
      high level of realism with respect to the human laryngeal anatomy. A non-linear
      spring-based contact force model is also implemented for the purpose of
      representing contact in more general conditions, especially those associated with
      three-dimensional modeling of phonation in the presence of vocal fold
      pathologies. The model is used to study the effects of a moderate (20%) vocal
      fold tension imbalance on the phonatory dynamics. The characteristic features of
      phonation for normal as well as tension-imbalanced vocal folds, such as glottal
      waveform, glottal jet evolution, mucosal wave-type vocal-fold motion, modal
      entrainment, and asymmetric glottal jet deflection have been discussed in detail
      and compared to established data. It is found that while a moderate level of
      tension asymmetry does not change the vibratory dynamics significantly, it can
      potentially lead to measurable deterioration in voice quality.

PMID- 22978891
TI  - Asymmetric vibration in a two-layer vocal fold model with left-right stiffness
      asymmetry: experiment and simulation.
AB  - Vibration characteristics of a self-oscillating two-layer vocal fold model with
      left-right asymmetry in body-layer stiffness were experimentally and numerically
      investigated. Two regimes of distinct vibratory pattern were identified as a
      function of left-right stiffness mismatch. In the first regime with extremely
      large left-right stiffness mismatch, phonation onset resulted from an eigenmode
      synchronization process that involved only eigenmodes of the soft fold. Vocal
      fold vibration in this regime was dominated by a large-amplitude vibration of the
      soft fold, and phonation frequency was determined by the properties of the soft
      fold alone. The stiff fold was only enslaved to vibrate at a much reduced
      amplitude. In the second regime with small left-right stiffness mismatch,
      eigenmodes of both folds actively participated in the eigenmode synchronization
      process. The two folds vibrated with comparable amplitude, but the stiff fold
      consistently led the soft fold in phase for all conditions. A qualitatively good
      agreement was obtained between experiment and simulation, although the
      simulations generally underestimated phonation threshold pressure and onset
      frequency. The clinical implications of the results of this study are also
      discussed.

PMID- 22978892
TI  - Mitigation of temporal aliasing via harmonic modeling of laryngeal waveforms in
      high-speed videoendoscopy.
AB  - High-speed videoendoscopy (HSV) enables the observation and measurement of
      vibratory behaviors of vocal folds by capturing the laryngeal imagery at high
      frame rates. The frame rates of commercially available HSVs, however, are still
      limited to carry out sample-based time-domain objective analyses. To mitigate the
      resulting lack of temporal resolution, existing studies have employed sum-of
      harmonics parametric models to evaluate temporal vocal-fold behaviors. This paper
      focuses on the other weakness of HSV: its inherent susceptibility to temporal
      aliasing. Aliasing occurs when there are substantial harmonics above the Nyquist
      frequency of the HSV camera, and video cameras offer very little means to filter
      out these harmonics. Although the aliasing effect in HSV data minimally affects
      many of the laryngeal objective parameter measurements, some parameters, such as
      harmonics-to-noise ratio and derivative-based parameters, are sensitive to the
      aliased content. The use of a parametric model with a careful selection of the
      number of harmonics enables classification of the aliased harmonics as a part of
      the harmonic signal. Glottal area waveform examples are included to illustrate
      the modeling capability for cases of normal and disordered vocal folds.

PMID- 22978893
TI  - Phoneme recognition in modulated maskers by normal-hearing and aided hearing
      impaired listeners.
AB  - This study measured the influence of masker fluctuations on phoneme recognition.
      The first part of the study compared the benefit of masker modulations for
      consonant and vowel recognition in normal-hearing (NH) listeners. Recognition
      scores were measured in steady-state and sinusoidally amplitude-modulated noise
      maskers (100% modulation depth) at several modulation rates and signal-to-noise
      ratios. Masker modulation rates were 4, 8, 16, and 32 Hz for the consonant
      recognition task and 2, 4, 12, and 32 Hz for the vowel recognition task. Vowel
      recognition scores showed more modulation benefit and a more pronounced effect of
      masker modulation rate than consonant scores. The modulation benefit for word
      recognition from other studies was found to be more similar to the benefit for
      vowel recognition than that for consonant recognition. The second part of the
      study measured the effect of modulation rate on the benefit of masker modulations
      for vowel recognition in aided hearing-impaired (HI) listeners. HI listeners
      achieved as much modulation benefit as NH listeners for slower masker modulation
      rates (2, 4, and 12 Hz), but showed a reduced benefit for the fast masker
      modulation rate of 32 Hz.

PMID- 22978894
TI  - Relationship between masking release in fluctuating maskers and speech reception
      thresholds in stationary noise.
AB  - In contrast to normal-hearing (NH) listeners, hearing-impaired (HI) listeners
      often show strongly reduced masking release (MR) in fluctuating interferers,
      which has commonly been associated with spectral and temporal processing
      deficits. However, it has recently been proposed that the reduced MR could result
      from an increased speech recognition threshold (SRT) in stationary noise
      [Bernstein and Grant, J. Acoust. Soc. Am. 125, 3358-3372 (2009)]. This was tested
      by presenting noise-band vocoded as well as low-pass and high-pass filtered
      stimuli to NH listeners, thereby increasing their stationary-noise SRTs to those
      of the HI listeners. If the primary determinant of MR is the SRT in stationary
      noise then the amount of the MR should be independent of the type of processing
      used to obtain the stationary-noise SRT. However, the relation between the amount
      of MR and the stationary-noise SRT depended on the type of processing. For a
      fluctuating interferer, none of the processing conditions reduced the MR of the
      NH listeners to that of the HI listeners. In contrast, for an interfering talker,
      the results for vocoded stimuli were similar to those of the HI listeners.
      Overall, these results suggest that the observed MR is only partially related to
      the stationary-noise SRT.

PMID- 22978895
TI  - The relative importance of consonant and vowel segments to the recognition of
      words and sentences: effects of age and hearing loss.
AB  - This study investigated the ability to use cues contained within vowel and
      consonant segments by older listeners with normal or impaired hearing. Spectral
      shaping restored audibility for the hearing-impaired group. Word and sentence
      materials were processed to contain primarily consonants or vowels by replacing
      segments with low-level speech-shaped noise. The proportion of the total duration
      of preserved speech was varied by manipulating the amount of transitional
      information contained within vowel and consonant segments. Older listeners
      performed more poorly than young listeners on all conditions except when
      listening to sentences with only the vowels preserved. Results confirmed a
      greater contribution to intelligibility of vowel segments in sentences, but not
      in words, for young normal-hearing, older normal-hearing, and older hearing
      impaired listeners. Older listeners received a greater benefit than young
      listeners from vowels presented in a sentence context. Correlation analyses among
      the older listeners demonstrated an association between consonant and vowel
      performance in isolated words but not in sentences. In addition, the use of vowel
      cues in sentences was relatively independent of age and auditory sensitivity when
      audibility is ensured. Combined, results argue that older listeners are able to
      use essential cues carried by vowels for sentence intelligibility.

PMID- 22978896
TI  - A correlational method to concurrently measure envelope and temporal fine
      structure weights: effects of age, cochlear pathology, and spectral shaping.
AB  - The speech signal may be divided into spectral frequency-bands, each band
      containing temporal properties of the envelope and fine structure. This study
      measured the perceptual weights for the envelope and fine structure in each of
      three frequency bands for sentence materials in young normal-hearing listeners,
      older normal-hearing listeners, aided older hearing-impaired listeners, and
      spectrally matched young normal-hearing listeners. The availability of each
      acoustic property was independently varied through noisy signal extraction. Thus,
      the full speech stimulus was presented with noise used to mask six different
      auditory channels. Perceptual weights were determined by correlating a listener's
      performance with the signal-to-noise ratio of each acoustic property on a trial
      by-trial basis. Results demonstrate that temporal fine structure perceptual
      weights remain stable across the four listener groups. However, a different
      weighting typography was observed across the listener groups for envelope cues.
      Results suggest that spectral shaping used to preserve the audibility of the
      speech stimulus may alter the allocation of perceptual resources. The relative
      perceptual weighting of envelope cues may also change with age. Concurrent
      testing of sentences repeated once on a previous day demonstrated that weighting
      strategies for all listener groups can change, suggesting an initial
      stabilization period or susceptibility to auditory training.

PMID- 22978897
TI  - Impact of talker variability on word recognition in non-native listeners.
AB  - This study investigates the perception of English words produced by 45 native
      talkers presented in moderate noise to native Norwegian listeners. The relative
      intelligibility of individual talkers is compared with that obtained for native
      listeners in order to determine whether intrinsic talker clarity is determined by
      global acoustic-phonetic characteristics. Talker intelligibility was strongly
      correlated across native and non-native listeners although the acoustic-phonetic
      characteristics that correlated with intelligibility varied across the two
      groups. For both groups, intelligibility was correlated with an amount of energy
      in the mid-frequency region, but whereas mean word duration was another relevant
      factor for the natives it was the F2 range in the vowel space for the non
      natives. There was also a strong correlation across groups as to the lexical
      items most often misperceived. Results for two different listening conditions
      (recognition of isolated words vs triplets) suggested that non-native performance
      was to a certain extent hampered by increased cognitive load in the triplet
      condition.

PMID- 22978899
TI  - Improving word recognition in noise among hearing-impaired subjects with a single
      channel cochlear noise-reduction algorithm.
AB  - A common complaint of the hearing impaired is the inability to understand speech
      in noisy environments even with their hearing assistive devices. Only a few
      single-channel algorithms have significantly improved speech intelligibility in
      noise for hearing-impaired listeners. The current study introduces a cochlear
      noise reduction algorithm. It is based on a cochlear representation of acoustic
      signals and real-time derivation of a binary speech mask. The contribution of the
      algorithm for enhancing word recognition in noise was evaluated on a group of 42
      normal-hearing subjects, 35 hearing-aid users, 8 cochlear implant recipients, and
      14 participants with bimodal devices. Recognition scores of Hebrew monosyllabic
      words embedded in Gaussian noise at several signal-to-noise ratios (SNRs) were
      obtained with processed and unprocessed signals. The algorithm was not effective
      among the normal-hearing participants. However, it yielded a significant
      improvement in some of the hearing-impaired subjects under different listening
      conditions. Its most impressive benefit appeared among cochlear implant
      recipients. More than 20% improvement in recognition score of noisy words was
      obtained by 12, 16, and 26 hearing-impaired at SNR of 30, 24, and 18 dB,
      respectively. The algorithm has a potential to improve speech intelligibility in
      background noise, yet further research is required to improve its performances.

PMID- 22978898
TI  - Effect of fundamental-frequency and sentence-onset differences on speech
      identification performance of young and older adults in a competing-talker
      background.
AB  - This study investigated the benefits of differences between sentences in
      fundamental frequency (F0) and temporal onset for sentence pairs among listener
      groups differing in age and hearing sensitivity. Two experiments were completed
      with the primary difference between experiments being the way in which the
      stimuli were presented. Experiment 1 used blocked stimulus presentation, which
      ultimately provided redundant acoustic cues to mark the target sentence in each
      pair, whereas Experiment 2 sampled a slightly more restricted stimulus space, but
      in a completely randomized presentation order. For both experiments, listeners
      were required to detect a cue word ("Baron") for the target sentence in each pair
      and to then identify the target words (color, number) that appeared later in the
      target sentence. Results of Experiment 1 showed that F0 or onset separation cues
      were beneficial to both cue-word detection and color-number identification
      performance. There were no significant differences across groups in the ability
      to detect the cue word, but groups differed in their ability to identify the
      correct color-number words. Elderly adults with impaired hearing had the greatest
      difficulty with the identification task despite the application of spectral
      shaping to restore the audibility of the speech stimuli. For the most part, the
      primary results of Experiment 1 were replicated in Experiment 2, although, in the
      latter experiment, all older adults, whether they had normal or impaired hearing,
      performed worse than young adults with normal hearing. From Experiment 2, the
      benefits received for a difference in F0 between talkers of 6 semitones were
      equivalent to those received for an onset asynchrony of 300 ms between sentences
      and, for such conditions, the combination of both sound-segregation cues resulted
      in an additive benefit.

PMID- 22978900
TI  - Kalman-based autoregressive moving average modeling and inference for formant and
      antiformant tracking.
AB  - Vocal tract resonance characteristics in acoustic speech signals are classically
      tracked using frame-by-frame point estimates of formant frequencies followed by
      candidate selection and smoothing using dynamic programming methods that minimize
      ad hoc cost functions. The goal of the current work is to provide both point
      estimates and associated uncertainties of center frequencies and bandwidths in a
      statistically principled state-space framework. Extended Kalman (K) algorithms
      take advantage of a linearized mapping to infer formant and antiformant
      parameters from frame-based estimates of autoregressive moving average (ARMA)
      cepstral coefficients. Error analysis of KARMA, wavesurfer, and praat is
      accomplished in the all-pole case using a manually marked formant database and
      synthesized speech waveforms. KARMA formant tracks exhibit lower overall root
      mean-square error relative to the two benchmark algorithms with the ability to
      modify parameters in a controlled manner to trade off bias and variance.
      Antiformant tracking performance of KARMA is illustrated using synthesized and
      spoken nasal phonemes. The simultaneous tracking of uncertainty levels enables
      practitioners to recognize time-varying confidence in parameters of interest and
      adjust algorithmic settings accordingly.

PMID- 22978901
TI  - Binaural interaction and the octave illusion.
AB  - The auditory octave illusion arises when dichotically presented tones, one octave
      apart, alternate rapidly between the ears. Most subjects perceive an illusory
      sequence of monaural tones: A high tone in the right ear (RE) alternates with a
      low tone, incorrectly localized to the left ear (LE). Behavioral studies suggest
      that the perceived pitch follows the RE input, and the perceived location the
      higher-frequency sound. To explore the link between the perceived pitches and
      brain-level interactions of dichotic tones, magnetoencephalographic responses
      were recorded to 4 binaural combinations of 2-min long continuous 400- and 800-Hz
      tones and to 4 monaural tones. Responses to LE and RE inputs were distinguished
      by frequency-tagging the ear-specific stimuli at different modulation
      frequencies. During dichotic presentation, ipsilateral LE tones elicited weaker
      and ipsilateral RE tones stronger responses than when both ears received the same
      tone. During the most paradoxical stimulus-high tone to LE and low tone to RE
      perceived as a low tone in LE during the illusion-also the contralateral
      responses to LE tones were diminished. The results demonstrate modified binaural
      interaction of dichotic tones one octave apart, suggesting that this interaction
      contributes to pitch perception during the octave illusion.

PMID- 22978902
TI  - Analysis of high-frequency energy in long-term average spectra of singing,
      speech, and voiceless fricatives.
AB  - The human singing and speech spectrum includes energy above 5 kHz. To begin an in
      depth exploration of this high-frequency energy (HFE), a database of anechoic
      high-fidelity recordings of singers and talkers was created and analyzed. Third
      octave band analysis from the long-term average spectra showed that production
      level (soft vs normal vs loud), production mode (singing vs speech), and phoneme
      (for voiceless fricatives) all significantly affected HFE characteristics.
      Specifically, increased production level caused an increase in absolute HFE
      level, but a decrease in relative HFE level. Singing exhibited higher levels of
      HFE than speech in the soft and normal conditions, but not in the loud condition.
      Third-octave band levels distinguished phoneme class of voiceless fricatives.
      Female HFE levels were significantly greater than male levels only above 11 kHz.
      This information is pertinent to various areas of acoustics, including vocal
      tract modeling, voice synthesis, augmentative hearing technology (hearing aids
      and cochlear implants), and training/therapy for singing and speech.

PMID- 22978903
TI  - Estimation of the acoustic range of bat echolocation for extended targets.
AB  - Extended natural structures of the bat environment such as trees, meadows, and
      water surfaces were ensonified in distances from 1 to 20 m and the echoes
      recorded using a mobile ultrasonic sonar system. By compensating the atmospheric
      attenuation, the attenuation of the reflected echo caused by diffraction, energy
      absorption of the target, and two-way-geometric spreading was calculated for each
      distance. For each target type the attenuation of the compensated echo sound
      pressure level was fitted over distance using a linear function which yields
      simple laws of reflection loss and geometric spreading. By adding to this
      function again variable atmospheric attenuation, the overall attenuation of a
      signal reflected from these targets can be estimated for various conditions.
      Given the dynamic range of a sonar system, the acoustic maximum detection
      distance can thus be estimated. The results show that the maximum range is
      dominantly limited by atmospheric attenuation. Energy loss in the reflecting
      surface is more variable than geometric spreading loss and accounts for most of
      the differences between the ensonified targets. Depending on atmospheric
      conditions, echolocation frequency, and the dynamic range of the sonar system,
      the maximum range for extended backgrounds such as a forest edge can be as short
      as 2.4 m.

PMID- 22978904
TI  - Bat wing air pressures may deflect prey structures to provide echo cues for
      detecting prey in clutter.
AB  - Bats have remarkable echolocation capabilities to detect prey in darkness. While
      it is clear how bats do this for prey that is isolated, moving, or noisy, their
      ability to find still and quiet prey within clutter has remained a mystery. A
      video published by the ChiRoPing group shows the gleaning bat Micronycteris
      microtis capturing a still dragonfly specimen sitting on a leaf surface. While
      hovering over the dragonfly, the bat's wings exert air forces that cause the
      dragonfly wings to deflect in synchrony with the bat's wing beats. This paper
      illustrates that echoes from such deflecting wings vary in both amplitude and
      time-of-flight, producing robust echo cues that permit prey detection, even when
      the prey is embedded within clutter. Experiments with a dragonfly specimen
      mounted on a leaf driven by periodic air puffs produced wing deflections that
      were sensed with sonar pulses. Results demonstrate that echo variations
      synchronized with periodic air puffs are easily distinguishable from surrounding
      clutter, even when clutter produces the first echoes. These results suggest a
      strategy that bats can employ to detect still and silent prey embedded within
      cluttered environments.

PMID- 22978905
TI  - Pulsed photoacoustic Doppler flowmetry using time-domain cross-correlation:
      accuracy, resolution and scalability.
AB  - The feasibility of making spatially resolved measurements of blood velocity using
      a pulsed photoacoustic Doppler technique in acoustic resolution mode has been
      investigated. Doppler time shifts were quantified via cross-correlation of
      photoacoustic waveform pairs generated within a blood-simulating phantom using
      pairs of light pulses. The phantom comprised micron-scale absorbers imprinted on
      an acetate sheet and moved at known velocities. The photoacoustic waves were
      detected using PZT ultrasound transducers operating at center frequencies of 20
      MHz, 5 MHz and 3.5 MHz; measurements of velocity and resolution were calculated
      from the mean cross-correlation function of 25 waveform pairs. Velocities in the
      range +/-0.15 to +/-1.5 ms(-1) were quantified with accuracies as low as 1%. The
      transducer focal beam width determines a maximum measurable velocity |V(max)|
      beyond which correlation is lost due to absorbers moving out of the focal beam
      between the two laser pulses. Below |V(max)| a measurement resolution of <4% of
      the measured velocity was achieved. Resolution and |V(max)| can be scaled to much
      lower velocities such as those encountered in microvasculature (< 50 mms(-1)).
      The advantage of pulsed rather than continuous-wave excitation is that spatially
      resolved velocity measurements can be made, offering the prospect of mapping flow
      within the microcirculation.

PMID- 22978906
TI  - The underwater acoustic activities of the red swamp crayfish Procambarus clarkii.
AB  - This study describes the underwater acoustic behavior of the red swamp crayfish
      Procambarus clarkii. The study was conducted both in a tank and in the natural
      environment. The tank was equipped with video and acoustic recording systems.
      Observations were conducted to identify the underwater acoustic signals produced
      and their association with behavioral events and the movement status of the
      animals. In a lake in a natural reserve, a remote acoustic recording station was
      used to study the circadian underwater acoustic activity of the crayfish and to
      assess the acoustic features of the signals. The red swamp crayfish produces
      irregular trains of wide-band pulses (duration 0.4 ms, SPL(PK) 128 dB re 1 MUPa,
      peak frequency 28 kHz, bandwidth(RMS) 20 kHz). The production of signals is
      positively related to intraspecific interactions (encounter/approach, fighting
      and successive Tail Flips). In the natural environment, acoustic activity is
      almost absent during the day, increases abruptly at sunset and continues until
      dawn. This study reveals the previously unknown underwater acoustic signals of
      Procambarus clarkii and the potential of passive acoustic methods to monitor the
      presence, the abundance and the behavioral activities of this invasive species.

PMID- 22978907
TI  - Silky sifaka (Propithecus candidus) "zzuss" vocalizations: sexual dimorphism,
      individuality, and function in the alarm call of a monomorphic lemur.
AB  - Vocalizations of Madagascar's lemurs have generally been less investigated than
      those of other primate groups, with virtually no information available about
      calling in the silky sifaka (Propithecus candidus), a large rainforest species.
      Current work examined the "zzuss" vocalization, one of the most common and
      loudest sounds produced by this monomorphic species, and included 160 calls from
      nine adults (five males, four females) in three groups. Analyses focused on
      overall acoustic features, individual and sex differences, call usage, and likely
      function. Acoustically, the calls included separable turbulent noise and tonal
      components, with the later often marked by frequency jumps and dramatic frequency
      modulation. Male and female zzuss calls differed most in F0- and amplitude
      related features, characteristics that are relatively unconstrained by overall
      body size. All measures differed among individual callers, with F0-related
      variables again playing the largest role. Based on usage, these calls most likely
      function both as generalized alarm and group-coordination signals. The sounds
      were thus of interest in several regards, including showing sexual
      differentiation in the absence of other dimorphisms, exhibiting primarily F0
      based differentiation in both sex- and individual-based comparisons, and
      combining apparent alarm and coordination functions across a variety of contexts.

PMID- 22978908
TI  - A whale better adjusts the biosonar to ordered rather than to random changes in
      the echo parameters.
AB  - A false killer whale's (Pseudorca crassidens) sonar clicks and auditory evoked
      potentials (AEPs) were recorded during echolocation with simulated echoes in two
      series of experiments. In the first, both the echo delay and transfer factor
      (which is the dB-ratio of the echo sound-pressure level to emitted pulse source
      level) were varied randomly from trial to trial until enough data were collected
      (random presentation). In the second, a combination of the echo delay and
      transfer factor was kept constant until enough data were collected (ordered
      presentation). The mean click level decreased with shortening the delay and
      increasing the transfer factor, more at the ordered presentation rather than at
      the random presentation. AEPs to the self-heard emitted clicks decreased with
      shortening the delay and increasing the echo level equally in both series. AEPs
      to echoes increased with increasing the echo level, little dependent on the echo
      delay at random presentations but much more dependent on delay with ordered
      presentations. So some adjustment of the whale's biosonar was possible without
      prior information about the echo parameters; however, the availability of prior
      information about echoes provided additional whale capabilities to adjust both
      the transmitting and receiving parts of the biosonar.

PMID- 22978909
TI  - Surface modes and acoustic scattering of microspheres and ultrasound contrast
      agents.
AB  - Surface modes of spherical objects subject to ultrasound excitation have been
      recently proposed to explain experimental measurements of scattering from
      microspheres and ultrasound contrast agents (UCAs). In this work, the
      relationship between surface modes and resonance frequencies of microspheres and
      UCAs is investigated. A finite-element model, built upon the fundamentals of wave
      propagation and structural mechanics, was introduced and validated against
      analytical solutions (error <5%). Numerical results showed the existence of a
      systematic relationship between resonance frequencies and surface modes of a 30
      MUm microsphere driven at 1-70 MHz. On the contrary, for a 100 nm shelled, 4 MUm
      diameter UCA, no clear relationship between the resonance frequencies and the
      surface modes was found in the frequency range examined. Instead, the UCA
      exhibited a collection of complex oscillations, which appear to be a combination
      of various surface modes and displacements. A study of the effects of varying the
      shell properties on the backscatter showed the presence of peaks in the
      backscatter of thick-shelled UCAs, which are not predicted by previous models. In
      summary, this work presents a systematic effort to examine scattering and surface
      modes from ultrasound contrast agents using finite-element models.

PMID- 22978910
TI  - Cancellous bone fast and slow waves obtained with Bayesian probability theory
      correlate with porosity from computed tomography.
AB  - A Bayesian probability theory approach for separating overlapping ultrasonic fast
      and slow waves in cancellous bone has been previously introduced. The goals of
      this study were to investigate whether the fast and slow waves obtained from
      Bayesian separation of an apparently single mode signal individually correlate
      with porosity and to isolate the fast and slow waves from medial-lateral
      insonification of the calcaneus. The Bayesian technique was applied to trabecular
      bone data from eight human calcanei insonified in the medial-lateral direction.
      The phase velocity, slope of attenuation (nBUA), and amplitude were determined
      for both the fast and slow waves. The porosity was assessed by micro-computed
      tomography (microCT) and ranged from 78.7% to 94.1%. The method successfully
      separated the fast and slow waves from medial-lateral insonification of the
      calcaneus. The phase velocity for both the fast and slow wave modes showed an
      inverse correlation with porosity (R(2) = 0.73 and R(2) = 0.86, respectively).
      The slope of attenuation for both wave modes also had a negative correlation with
      porosity (fast wave: R(2) = 0.73, slow wave: R(2) = 0.53). The fast wave
      amplitude decreased with increasing porosity (R(2) = 0.66). Conversely, the slow
      wave amplitude modestly increased with increasing porosity (R(2) = 0.39).

PMID- 22979828
TI  - A quieting ocean: unintended consequence of a fluctuating economy.
AB  - Simultaneous long-term monitoring of underwater sound and ship traffic provided
      an opportunity to study how low-frequency noise correlated with ocean-based
      commercial shipping trends. Between 2007 and 2010 changes in regional shipping
      off southern California occurred as a consequence of economic and regulatory
      events. Underwater average noise levels measured before and during these events
      showed a net reduction of 12 dB. Statistical models revealed that a reduction of
      1 ship transit per day resulted in 1 dB decrease in average noise. This synthesis
      of maritime traffic statistics with ocean noise monitoring provides an important
      step in understanding the magnitude and potential effects of chronic noise in
      marine habitats.

PMID- 22979829
TI  - Seasonal presence of cetaceans and ambient noise levels in polar waters of the
      North Atlantic.
AB  - In 2009 two calibrated acoustic recorders were deployed in polar waters of the
      North Atlantic to study the seasonal occurrence of blue, fin, and sperm whales
      and to assess current ambient noise levels. Sounds from these cetaceans were
      recorded at both locations in most months of the year. During the summer months,
      seismic airguns associated with oil and gas exploration were audible for weeks at
      a time and dominated low frequency noise levels. Noise levels might further
      increase in the future as the receding sea ice enables extended human use of the
      area.

PMID- 22979830
TI  - Elastic Pekeris waveguide normal mode solution comparisons against laboratory
      data.
AB  - Following the derivation presented by Press and Ewing [Geophysics 15, 426-446
      (1950)], a normal mode solution for the Pekeris waveguide problem with an elastic
      bottom is outlined. The analytic solution is benchmarked against data collected
      in an experiment performed at the Naval Research Laboratory [Collis et al., J.
      Acoust. Soc. Am. 122, 1987-1993 (2007)]. Comparisons reveal a close match between
      the analytic solution and experimental data. Results are strongly dependent on
      the accuracy of the horizontal wavenumbers for the modes, and horizontal
      wavenumber spectra are compared against those from the experimental data.

PMID- 22979831
TI  - Formant discrimination of speech and non-speech sounds for English and Chinese
      listeners.
AB  - Thresholds of formant discrimination of speech and non-speech sounds were
      compared for native listeners of English and Chinese. English listeners showed
      significantly better thresholds than Chinese listeners, not only for English
      vowels, but also for Chinese vowels. Thresholds for vowel-spectrum-shaped noise
      were comparable for the two groups. These results suggest that English listeners
      are more sensitive to formant frequency changes of vowel stimuli than Chinese
      listeners, possibly due to the denser vowel space for English than for Mandarin
      Chinese. However, the psychophysical capacity to discriminate formant frequency
      changes in non-speech sounds is similar for English and Chinese listeners.

PMID- 22979832
TI  - Increased intensity discrimination thresholds in tinnitus subjects with a normal
      audiogram.
AB  - Recent auditory brain stem response measurements in tinnitus subjects with normal
      audiograms indicate the presence of hidden hearing loss that manifests as reduced
      neural output from the cochlea at high sound intensities, and results from mice
      suggest a link to deafferentation of auditory nerve fibers. As deafferentation
      would lead to deficits in hearing performance, the present study investigates
      whether tinnitus patients with normal hearing thresholds show impairment in
      intensity discrimination compared to an audiometrically matched control group.
      Intensity discrimination thresholds were significantly increased in the tinnitus
      frequency range, consistent with the hypothesis that auditory nerve fiber
      deafferentation is associated with tinnitus.

PMID- 22979833
TI  - Nonlinear ultrasound: potential of the cross-correlation method for
      osseointegration monitoring.
AB  - Recently the concept of probing nonlinear elasticity at an interface
      prosthesis/bone has been proposed as a promising method to monitor the
      osseointegration/sealing of a prosthesis. However, the most suitable method to
      achieve this goal is a point of debate. To this purpose, two approaches termed
      the scaling subtraction method and the cross-correlation method are compared
      here. One nonlinear parameter derived from the cross-correlation method is as
      sensitive as a clinical device based on linear elasticity measurement. Further,
      this study shows that cross-correlation based methods are more sensitive than
      those based on subtraction/addition, such like pulse inversion and similar
      methods.

PMID- 22979834
TI  - Interpreting tone of voice: musical pitch relationships convey agreement in
      dyadic conversation.
AB  - Previous research has found that the musical intervals found in speech are
      associated with various emotions. Intervals can be classified by their level of
      consonance or dissonance-how pleasant or unpleasant the combined tones sound to
      the ear. Exploratory investigations have indicated that in an agreeable
      conversation, the pitches of the last word in an utterance and the first word of
      a conversation partner's utterance are consonantly related; in a disagreeable
      conversation, the two pitches are dissonantly related. The present results showed
      that the intervals between the tonics of the utterances in a conversation
      corresponded to the agreement between interlocutors.

PMID- 22979835
TI  - Coherence length as a figure of merit in multireference near-field acoustical
      holography.
AB  - Multireference partial field decomposition (PFD) can be used to generate coherent
      holograms for near-field acoustical holography measurements. PFD is most
      successful when the reference array completely senses all independent subsources,
      but meeting this requirement is not straightforward when the number of subsources
      and their locations are ambiguous (such as in aeroacoustic sources). A figure of
      merit based on spatial coherence lengths, called references per coherence length
      (RPL(C)), is a useful metric to guide inter-reference spacing in the array
      design. For numerical, extended, arbitrarily coherent sources one reference per
      coherence length results in a sufficient reference array.

PMID- 22979836
TI  - Slow and fast ultrasonic wave detection improvement in human trabecular bones
      using Golay code modulation.
AB  - The identification of fast and slow waves propagating through trabecular bone is
      a challenging task due to temporal wave overlap combined with the high
      attenuation of the fast wave in the presence of noise. However, it can provide
      valuable information about bone integrity and become a means for monitoring
      osteoporosis. The objective of this work is to apply different coded excitation
      methods for this purpose. The results for single-sine cycle pulse, Golay code,
      and chirp excitations are compared. It is shown that Golay code is superior to
      the other techniques due to its signal enhancement while exhibiting excellent
      resolution without the ambiguity of sidelobes.

PMID- 22979837
TI  - Radiated noise from commercial ships in the Gulf of Maine: implications for
      whale/vessel collisions.
AB  - To understand mysticete acoustic-based detection of ships, radiated noise from
      high-speed craft, cruise ships, catamarans and fishing vessels was recorded June
      September 2009. Calibrated acoustic data (<2500 Hz) from a vertical hydrophone
      array was combined with ship passage information. A cruise ship had the highest
      broadband source level, while a fishing vessel had the lowest. Ship noise
      radiated asymmetrically and varied with depth. Bow null-effect acoustic shadow
      zones were observed for all ship classes and were correlated with ship-length-to
      draft-ratios. These shadow zones may reduce ship detection by near-surface
      mysticetes.

PMID- 22979838
TI  - A numerical study of a method for measuring the effective in situ sound
      absorption coefficient.
AB  - The accuracy of a method [Wijnant et al., Proc. of ISMA 31, Leuven, Belgium
      (2010), Vol. 31] for measurement of the effective area-averaged in situ sound
      absorption coefficient is investigated. Based on a local plane wave assumption,
      this method can be applied to sound fields for which a model is not available.
      Investigations were carried out by means of finite element simulations for a
      typical case. The results show that the method is a promising method for
      determining the effective area-averaged in situ sound absorption coefficient in
      complex sound fields.

PMID- 22979839
TI  - Ultrasonic Doppler methods to extract signatures of a walking human.
AB  - Extraction of Doppler signatures that characterize human motion has attracted a
      growing interest in recent years. These Doppler signatures are generated by
      various components of the human body while walking, and contain unique features
      that can be used for human detection and recognition. Although, a significant
      amount of research has been done in radio frequency regime for human Doppler
      signature extraction, considerably less has been done in acoustics. In this work,
      40 kHz ultrasonic sonar is employed to measure the Doppler signature generated by
      the motion of body segments using different electronic and signal processing
      schemes. These schemes are based on both analog and digital demodulation with
      homodyne and heterodyne receiver circuitry. The results and analyses from these
      different schemes are presented.

PMID- 22979840
TI  - Measurement of stop consonant identification using adaptive tracking procedures.
AB  - The purpose of this study was to establish the potential utility of adaptive
      tracking procedures, relative to the method of constant stimuli, when examining
      consonant identification in cafeteria noise or four-talker babble. Thresholds for
      consonant identification were comparable for the two methods, while psychometric
      function slopes derived from the two methods were statistically different. To
      obtain accurate slope estimates from adaptive procedures, the target percent
      correct and change in variability with signal-to-noise ratio should be considered
      carefully. However, adaptive procedures are accurate and more efficient than the
      method of constant stimuli when the purpose is to estimate phoneme identification
      threshold.

PMID- 22979841
TI  - Communication: From graphite to diamond: reaction pathways of the phase
      transition.
AB  - Phase transitions between carbon allotropes are calculated using the generalized
      solid-state nudged elastic band method. We find a new reaction mechanism between
      graphite and diamond with nucleation characteristics that has a lower activation
      energy than the concerted mechanism. The calculated barrier from graphite to
      hexagonal diamond is lower than to cubic diamond, resolving a conflict between
      theory and experiment. Transitions are calculated to three structures of cold
      compressed graphite: bct C4, M, and Z-carbon, which are accessible at the
      experimentally relevant pressures near 17 GPa.

PMID- 22979842
TI  - Communication: Magnetic dipole transitions in the OH A 2Sigma+ <- X 2Pi system.
AB  - We report on the observation of magnetic dipole allowed transitions in the well
      characterized A (2)Sigma(+) - X (2)Pi band system of the OH radical. A Stark
      decelerator in combination with microwave Rabi spectroscopy is used to control
      the populations in selected hyperfine levels of both Lambda-doublet components of
      the X (2)Pi(3/2), v = 0, J = 3/2 ground state. Theoretical calculations presented
      in this Communication predict that the magnetic dipole transitions in the A
      (2)Sigma(+), v = 1 <- X (2)Pi, v = 0 band are weaker than the electric dipole
      transitions by a factor of 2.58 * 10(3) only, i.e., much less than commonly
      believed. Our experimental data confirm this prediction.

PMID- 22979843
TI  - Communication: Phase space wavelets for solving Coulomb problems.
AB  - Recently we introduced a phase space approach for solving the time-independent
      Schrodinger equation using a periodic von Neumann basis with bi-orthogonal
      exchange (pvb) [A. Shimshovitz and D. J. Tannor, Phys. Rev. Lett. 109, 070402
      (2012)]. Here we extend the approach to allow a wavelet scaling of the phase
      space Gaussians. The new basis set, which we call the wavelet pvb basis, is
      simple to implement and provides an appealing alternative to other wavelet
      approaches. For the 1D Coulomb problems tested in this paper, the method reduces
      the size of the basis relative to the Fourier grid method by a factor of 13-60.
      The savings in basis set size is predicted to grow steeply as the dimensionality
      increases.

PMID- 22979845
TI  - Multi-scale multireference configuration interaction calculations for large
      systems using localized orbitals: partition in zones.
AB  - A new multireference configuration interaction method using localised orbitals is
      proposed, in which a molecular system is divided into regions of unequal
      importance. The advantage of dealing with local orbitals, i.e., the possibility
      to neglect long range interaction is enhanced. Indeed, while in the zone of the
      molecule where the important phenomena occur, the interaction cut off may be as
      small as necessary to get relevant results, in the most part of the system it can
      be taken rather large, so that results of good quality may be obtained at a lower
      cost. The method is tested on several systems. In one of them, the definition of
      the various regions is not based on topological considerations, but on the
      nature, sigma or pi, of the localised orbitals, which puts in evidence the
      generality of the approach.

PMID- 22979844
TI  - An adaptive weighted ensemble procedure for efficient computation of free
      energies and first passage rates.
AB  - We introduce an adaptive weighted-ensemble procedure (aWEP) for efficient and
      accurate evaluation of first-passage rates between states for two-state systems.
      The basic idea that distinguishes aWEP from conventional weighted-ensemble (WE)
      methodology is the division of the configuration space into smaller regions and
      equilibration of the trajectories within each region upon adaptive partitioning
      of the regions themselves into small grids. The equilibrated
      conditional/transition probabilities between each pair of regions lead to the
      determination of populations of the regions and the first-passage times between
      regions, which in turn are combined to evaluate the first passage times for the
      forward and backward transitions between the two states. The application of the
      procedure to a non-trivial coarse-grained model of a 70-residue calcium binding
      domain of calmodulin is shown to efficiently yield information on the equilibrium
      probabilities of the two states as well as their first passage times. Notably,
      the new procedure is significantly more efficient than the canonical
      implementation of the WE procedure, and this improvement becomes even more
      significant at low temperatures.

PMID- 22979846
TI  - Computing many-body wave functions with guaranteed precision: the first-order
      Moller-Plesset wave function for the ground state of helium atom.
AB  - We present an approach to compute accurate correlation energies for atoms and
      molecules using an adaptive discontinuous spectral-element multiresolution
      representation for the two-electron wave function. Because of the exponential
      storage complexity of the spectral-element representation with the number of
      dimensions, a brute-force computation of two-electron (six-dimensional) wave
      functions with high precision was not practical. To overcome the key storage
      bottlenecks we utilized (1) a low-rank tensor approximation (specifically, the
      singular value decomposition) to compress the wave function, and (2) explicitly
      correlated R12-type terms in the wave function to regularize the Coulomb electron
      electron singularities of the Hamiltonian. All operations necessary to solve the
      Schrodinger equation were expressed so that the reconstruction of the full-rank
      form of the wave function is never necessary. Numerical performance of the method
      was highlighted by computing the first-order Moller-Plesset wave function of a
      helium atom. The computed second-order Moller-Plesset energy is precise to ~2
      microhartrees, which is at the precision limit of the existing general atomic
      orbital-based approaches. Our approach does not assume special geometric
      symmetries, hence application to molecules is straightforward.

PMID- 22979847
TI  - Fourier space approach to the classical density functional theory for multi
      Yukawa and square-well fluids.
AB  - We present a Fourier space density functional approach for hard particles with
      attractive interactions, which is based on a previously developed two-dimensional
      approach [S. Hlushak, W. Rzysko, and S. Sokolowski, J. Chem. Phys. 131, 094904
      (2009)] for hard-sphere chains. The interactions are incorporated by means of a
      three-dimensional Fourier image of the direct correlation function that is
      obtained from the first-order mean-spherical approximation. In order to improve
      the computational efficiency, we make extensive use of fast Fourier transforms
      for calculating density convolution integrals. A two-dimensional implementation
      of the new density functional approach, based on the expansion of the functional
      around the bulk fluid density, is used to study structure and adsorption of two
      model fluids in narrow cylindrical pores. We also investigate two methods that
      improve the accuracy of the theory as compared to the conventional DFT approach,
      which expands the free energy functional around the bulk fluid density: One a
      variant of the reference fluid density functional theory used by Gillespie et al.
      [Phys. Rev. E 68, 031503 (2003)], and the second a weighted density approach with
      energy route thermodynamics. Results from these two methods are compared to the
      conventional approach and also to the results of Monte Carlo simulations. We find
      that the method of Gillespie et al. and the weighted density approach with energy
      route thermodynamics yield significant improvement over the conventional
      approach.

PMID- 22979848
TI  - Completeness-optimized basis sets: application to ground-state electron momentum
      densities.
AB  - In the current work we apply the completeness-optimization paradigm [P. Manninen
      and J. Vaara, J. Comput. Chem. 27, 434 (2006)] to investigate the basis set
      convergence of the moments of the ground-state electron momentum density at the
      self-consistent field level of theory. We present a black-box completeness
      optimization algorithm that can be used to generate computationally efficient
      basis sets for computing any property at any level of theory. We show that the
      complete basis set (CBS) limit of the moments of the electron momentum density
      can be reached more cost effectively using completeness-optimized basis sets than
      using conventional, energy-optimized Gaussian basis sets. By using the
      established CBS limits, we generate a series of smaller basis sets which can be
      used to systematically approach the CBS and to perform calculations on larger,
      experimentally interesting systems.

PMID- 22979850
TI  - Highly tunable spin-dependent electron transport through carbon atomic chains
      connecting two zigzag graphene nanoribbons.
AB  - Motivated by recent experiments of successfully carving out stable carbon atomic
      chains from graphene, we investigate a device structure of a carbon chain
      connecting two zigzag graphene nanoribbons with highly tunable spin-dependent
      transport properties. Our calculation based on the non-equilibrium Green's
      function approach combined with the density functional theory shows that the
      transport behavior is sensitive to the spin configuration of the leads and the
      bridge position in the gap. A bridge in the middle gives an overall good coupling
      except for around the Fermi energy where the leads with anti-parallel spins
      create a small transport gap, while the leads with parallel spins give a finite
      density of states and induce an even-odd oscillation in conductance in terms of
      the number of atoms in the carbon chain. On the other hand, a bridge at the edge
      shows a transport behavior associated with the spin-polarized edge states,
      presenting sharp pure alpha-spin and beta-spin peaks beside the Fermi energy in
      the transmission function. This makes it possible to realize on-chip
      interconnects or spintronic devices by tuning the spin state of the leads and the
      bridge position.

PMID- 22979849
TI  - Implicit ligand theory: rigorous binding free energies and thermodynamic
      expectations from molecular docking.
AB  - A rigorous formalism for estimating noncovalent binding free energies and
      thermodynamic expectations from calculations in which receptor configurations are
      sampled independently from the ligand is derived. Due to this separation,
      receptor configurations only need to be sampled once, facilitating the use of
      binding free energy calculations in virtual screening. Demonstrative calculations
      on a host-guest system yield good agreement with previous free energy
      calculations and isothermal titration calorimetry measurements. Implicit ligand
      theory provides guidance on how to improve existing molecular docking algorithms
      and insight into the concepts of induced fit and conformational selection in
      noncovalent macromolecular recognition.

PMID- 22979852
TI  - Rovibrationally selected ion-molecule collision study using the molecular beam
      vacuum ultraviolet laser pulsed field ionization-photoion method: charge transfer
      reaction of N2(+)(X 2Sigmag+; v+ = 0-2; N+ = 0-9) + Ar.
AB  - We have developed an ion-molecule reaction apparatus for state-selected absolute
      total cross section measurements by implementing a high-resolution molecular beam
      vacuum ultraviolet (VUV) laser pulsed field ionization-photoion (PFI-PI) ion
      source to a double-quadrupole double-octopole ion-guide mass spectrometer. Using
      the total cross section measurement of the state-selected N(2)(+)(v(+), N(+)) +
      Ar charge transfer (CT) reaction as an example, we describe in detail the design
      of the VUV laser PFI-PI ion source used, which has made possible the preparation
      of reactant N(2)(+)(X (2)Sigma(g)(+), v(+) = 0-2, N(+) = 0-9) PFI-PIs with high
      quantum state purity, high intensity, and high kinetic energy resolution. The PFI
      PIs and prompt ions produced in the ion source are shown to have different
      kinetic energies, allowing the clean rejection of prompt ions from the PFI-PI
      beam by applying a retarding potential barrier upstream of the PFI-PI source. By
      optimizing the width and amplitude of the pulsed electric fields employed to the
      VUV-PFI-PI source, we show that the reactant N(2)(+) PFI-PI beam can be formed
      with a laboratory kinetic energy resolution of DeltaE(lab) = +/- 50 meV. As a
      result, the total cross section measurement can be conducted at center-of-mass
      kinetic energies (E(cm)'s) down to thermal energies. Absolute total
      rovibrationally selected cross sections sigma(v(+) = 0-2, N(+) = 0-9) for the
      N(2)(+)(X (2)Sigma(g)(+); v(+) = 0-2, N(+) = 0-9) + Ar CT reaction have been
      measured in the E(cm) range of 0.04-10.0 eV, revealing strong vibrational
      enhancements and E(cm)-dependencies of sigma(v(+) = 0-2, N(+) = 0-9). The
      thermochemical threshold at E(cm) = 0.179 eV for the formation of Ar(+) from
      N(2)(+)(X; v(+) = 0, N(+)) + Ar was observed by the measured sigma(v(+) = 0),
      confirming the narrow DeltaE(cm) spread achieved in the present study. The
      sigma(v(+) = 0-2; N(+)) values obtained here are compared with previous
      experimental and theoretical results. The theoretical predictions calculated
      based on the Landau-Zener-Stuckelberg formulism are found to be in fair agreement
      with the present measured sigma(v(+) = 1 or 2; N(+)). Taking into account of the
      experimental uncertainties, the measured sigma(v(+) = 1 or 2, N(+)) for N(+) = 0
      9 at E(cm) = 0.04-10.0 eV are found to be independent of N(+).

PMID- 22979851
TI  - Zero-quantum stochastic dipolar recoupling in solid state nuclear magnetic
      resonance.
AB  - We present the theoretical description and experimental demonstration of a zero
      quantum stochastic dipolar recoupling (ZQ-SDR) technique for solid state nuclear
      magnetic resonance (NMR) studies of (13)C-labeled molecules, including proteins,
      under magic-angle spinning (MAS). The ZQ-SDR technique combines zero-quantum
      recoupling pulse sequence blocks with randomly varying chemical shift precession
      periods to create randomly amplitude- and phase-modulated effective homonuclear
      magnetic dipole-dipole couplings. To a good approximation, couplings between
      different (13)C spin pairs become uncorrelated under ZQ-SDR, leading to spin
      dynamics (averaged over many repetitions of the ZQ-SDR sequence) that are fully
      described by an orientation-dependent N * N polarization transfer rate matrix for
      an N-spin system, with rates that are inversely proportional to the sixth power
      of internuclear distances. Suppression of polarization transfers due to non
      commutivity of pairwise couplings (i.e., dipolar truncation) does not occur under
      ZQ-SDR, as we show both analytically and numerically. Experimental demonstrations
      are reported for uniformly (13)C-labeled L-valine powder (at 14.1 T and 28.00 kHz
      MAS), uniformly (13)C-labeled protein GB1 in microcrystalline form (at 17.6 T and
      40.00 kHz MAS), and partially labeled (13)C-labeled protein GB1 (at 14.1 T and
      40.00 kHz MAS). The experimental results verify that spin dynamics under ZQ-SDR
      are described accurately by rate matrices and suggest the utility of ZQ-SDR in
      structural studies of (13)C-labeled solids.

PMID- 22979853
TI  - Refined theoretical study of radiative association: cross sections and rate
      constants for the formation of SiN.
AB  - Radiative association of silicon mononitride (SiN) in its two lowest molecular
      electronic states is studied through quantum and classical dynamics. Special
      attention is paid to the behavior of the cross section at high collision
      energies. A modified expression for the semiclassical cross section is presented
      which excludes transitions to continuum states. This gives improved agreement
      with quantum mechanical perturbation theory at high energies. The high energy
      cross section is overestimated if conventional semiclassical theory is used. The
      modified semiclassical theory should be valid in general for radiative
      association transitions from an upper to a lower electronic state. We also
      implement a quantum dynamical optical potential method with the same type of
      modification. The rate coefficient is calculated using Breit-Wigner theory and
      the modified semiclassical formula for the resonance and direct contributions,
      respectively, for temperatures from 10 K to 20,000 K. A rapid decrease in the
      rate constant for formation of ground state SiN is observed above 2000 K which
      was not seen previously.

PMID- 22979854
TI  - Cold collisions of polyatomic molecular radicals with S-state atoms in a magnetic
      field: an ab initio study of He + CH2(X) collisions.
AB  - We develop a rigorous quantum mechanical theory for collisions of polyatomic
      molecular radicals with S-state atoms in the presence of an external magnetic
      field. The theory is based on a fully uncoupled space-fixed basis set
      representation of the multichannel scattering wave function. Explicit expressions
      are presented for the matrix elements of the scattering Hamiltonian for spin-1/2
      and spin-1 polyatomic molecular radicals interacting with structureless targets.
      The theory is applied to calculate the cross sections and thermal rate constants
      for spin relaxation in low-temperature collisions of the prototypical organic
      molecule methylene [CH(2)(X(3)B(1))] with He atoms. To this end, two accurate
      three-dimensional potential energy surfaces (PESs) of the He-CH(2)(X(3)B(1))
      complex are developed using the state-of-the-art coupled-cluster method including
      single and double excitations along with a perturbative correction for triple
      excitations and large basis sets. Both PESs exhibit shallow minima and are weakly
      anisotropic. Our calculations show that spin relaxation in collisions of CH(2),
      CHD, and CD(2) molecules with He atoms occurs at a much slower rate than elastic
      scattering over a large range of temperatures (1 MUK-1 K) and magnetic fields
      (0.01-1 T), suggesting excellent prospects for cryogenic helium buffer-gas
      cooling of ground-state ortho-CH(2)(X(3)B(1)) molecules in a magnetic trap.
      Furthermore, we find that ortho-CH(2) undergoes collision-induced spin relaxation
      much more slowly than para-CH(2), which indicates that magnetic trapping can be
      used to separate nuclear spin isomers of open-shell polyatomic molecules.

PMID- 22979855
TI  - Infrared spectroscopy of hydrated naphthalene cluster anions.
AB  - We present infrared spectra of mass-selected C(10)H(8)(-).(H(2)O)(n).Ar(m)
      cluster anions (n = 1-6) obtained by Ar predissociation spectroscopy. The
      experimental spectra are compared with predicted spectra from density functional
      theory calculations. The OH groups of the water ligands are involved in H-bonds
      to other water molecules or to the pi system of the naphthalene anion, which
      accommodates the excess electron. The interactions in the water network are
      generally found to be more important than those between water molecules and the
      ion. For 2 <= n <= 4 the water molecules form single layer water networks on one
      side of the naphthalene anion, while for n = 5 and 6, cage and multilayer
      structures become more energetically favorable. For cluster sizes with more than
      3 water molecules, multiple conformers are likely to be responsible for the
      experimental spectra.

PMID- 22979856
TI  - The water hexamer: three-body interactions, structures, energetics, and OH
      stretch spectroscopy at finite temperature.
AB  - Using a newly developed and recently parameterized classical empirical simulation
      model for water that involves explicit three-body interactions, we determine the
      eleven most stable isomers of the water hexamer. We find that the lowest energy
      isomer is one of the cage structures, in agreement with far-IR and microwave
      experiments. The energy ordering for the binding energies is cage > glove > book
      > bag > chair > boat > chaise, and energies relative to the cage are in good
      agreement with CCSD(T) calculations. The three-body contributions to the cage,
      book, and chair are also in reasonable agreement with CCSD(T) results. The energy
      of each isomer results from a delicate balance involving the number of hydrogen
      bonds, the strain of these hydrogen bonds, and cooperative and anti-cooperative
      three-body interactions, whose contribution we can understand simply from the
      form of the three-body interactions in the simulation model. Oxygen-oxygen
      distances in the cage and book isomers are in good agreement with microwave
      experiments. Hydrogen-bond distances depend on both donor and acceptor, which can
      again be understood from the three-body model. Fully anharmonic OH-stretch
      spectra are calculated for these low-energy structures, and compared with shifted
      harmonic results from ab initio and density functional theory calculations.
      Replica-exchange molecular dynamics simulations were performed from 40 to 194 K,
      which show that the cage isomer has the lowest free energy from 0 to 70 K, and
      the book isomer has the lowest free energy from 70 to 194 K. OH-stretch spectra
      were calculated between 40 and 194 K, and results at 40, 63, and 79 K were
      compared to recent experiments, leading to re-assignment of the peaks in the
      experimental spectra. We calculate local OH-stretch cumulative spectral densities
      for different donor-acceptor types and compare to analogous results for liquid
      water.

PMID- 22979857
TI  - Radical ions with nearly degenerate ground state: correlation between the rate of
      spin-lattice relaxation and the structure of adiabatic potential energy surface.
AB  - Paramagnetic spin-lattice relaxation (SLR) in radical cations (RCs) of the
      cycloalkane series in liquid solution was studied and analyzed from the point of
      view of the correlation between the relaxation rate and the structure of the
      adiabatic potential energy surface (PES) of the RCs. SLR rates in the RCs formed
      in x-ray irradiated n-hexane solutions of the cycloalkanes studied were measured
      with the method of time-resolved magnetic field effect in the recombination
      fluorescence of spin-correlated radical ion pairs. Temperature and, for some
      cycloalkanes, magnetic field dependences of the relaxation rate were determined.
      It was found that the conventional Redfield theory of the paramagnetic relaxation
      as applied to the results on cyclohexane RC, gave a value of about 0.2 ps for the
      correlation time of the perturbation together with an unrealistically high value
      of 0.1 T in field units for the matrix element of the relaxation transition. The
      PES structure was obtained with the DFT quantum-chemical calculations. It was
      found that for all of the cycloalkanes RCs considered, including low symmetric
      alkyl-substituted ones, the adiabatic PESes were surfaces of pseudorotation due
      to avoided crossing. In the RCs studied, a correlation between the SLR rate and
      the calculated barrier height to the pseudorotation was revealed. For RCs with a
      higher relaxation rate, the apparent activation energies for the SLR were similar
      to the calculated heights of the barrier. To rationalize the data obtained it was
      assumed that the vibronic states degeneracy, which is specific for Jahn-Teller
      active cyclohexane RC, was approximately kept in the RCs of substituted
      cycloalkanes for the vibronic states with the energies above and close to the
      barrier height to the pseudorotation. It was proposed that the effective spin
      lattice relaxation in a radical with nearly degenerate low-lying vibronic states
      originated from stochastic crossings of the vibronic levels that occur due to
      fluctuations of the interaction between the radical and the solvent. The
      magnitude of these fluctuations, ~100 cm(-1), determines the upper scale of the
      unperturbed splitting between the vibronic states, for which the manifestation of
      this paramagnetic relaxation mechanism could be expected. Our estimate for the
      relaxation rate derived using standard Landau-Zener model of nonadiabatic
      transitions at the level crossing agrees with the experimental data. This
      paramagnetic relaxation mechanism can also be operative in paramagnetic species
      of other types such as linear radicals, radicals with threefold degeneracy,
      paramagnetic centers in crystals, etc. It looks likely that the proposed SLR
      mechanism can be quenched by a fast vibrational relaxation in radicals.

PMID- 22979858
TI  - Effect of laser pulse shaping parameters on the fidelity of quantum logic gates.
AB  - The effect of varying parameters specific to laser pulse shaping instruments on
      resulting fidelities for the ACNOT(1), NOT(2), and Hadamard(2) quantum logic
      gates are studied for the diatomic molecule (12)C(16)O. These parameters include
      varying the frequency resolution, adjusting the number of frequency components
      and also varying the amplitude and phase at each frequency component. A time
      domain analytic form of the original discretized frequency domain laser pulse
      function is derived, providing a useful means to infer the resulting pulse shape
      through variations to the aforementioned parameters. We show that amplitude
      variation at each frequency component is a crucial requirement for optimal laser
      pulse shaping, whereas phase variation provides minimal contribution. We also
      show that high fidelity laser pulses are dependent upon the frequency resolution
      and increasing the number of frequency components provides only a small
      incremental improvement to quantum gate fidelity. Analysis through use of the
      pulse area theorem confirms the resulting population dynamics for one or two
      frequency high fidelity laser pulses and implies similar dynamics for more
      complex laser pulse shapes. The ability to produce high fidelity laser pulses
      that provide both population control and global phase alignment is attributed
      greatly to the natural evolution phase alignment of the qubits involved within
      the quantum logic gate operation.

PMID- 22979859
TI  - Spectroscopy and dynamics of the predissociated, quasi-linear S2 state of
      chlorocarbene.
AB  - In this work, we report on the spectroscopy and dynamics of the quasi-linear S(2)
      state of chlorocarbene, CHCl, and its deuterated isotopologue using optical
      optical double resonance (OODR) spectroscopy through selected rovibronic levels
      of the S(1) state. This study, which represents the first observation of the S(2)
      state in CHCl, builds upon our recent examination of the corresponding state in
      CHF, where pronounced mode specificity was observed in the dynamics, with
      predissociation rates larger for levels containing bending excitation. In the
      present work, a total of 14 S(2) state vibrational levels with angular momentum l
      = 1 were observed for CHCl, and 34 levels for CDCl. The range of l in this case
      was restricted by the pronounced Renner-Teller effect in the low-lying S(1)
      levels, which severely reduces the fluorescence lifetime for levels with K(a) >
      0. Nonetheless, by exploiting different intermediate S(1) levels, we observed
      progressions involving all three fundamental vibrations. For levels with long
      predissociation lifetimes, rotational constants were determined by measuring
      spectra through different intermediate J levels of the S(1) state. Plots of the
      predissociation linewidth (lifetime) vs. energy for various S(2) levels show an
      abrupt onset, which lies near the calculated threshold for elimination to form
      C((3)P) + HCl on the triplet surface. Our experimental results are compared with
      a series of high level ab initio calculations, which included the use of a
      dynamically weighted full-valence CASSCF procedure, focusing maximum weight on
      the state of interest (the singlet and triplet states were computed separately).
      This was used as the reference for subsequent Davidson-corrected MRCI(+Q)
      calculations. These calculations reveal the presence of multiple conical
      intersections in the singlet manifold.

PMID- 22979860
TI  - Structures of N2Ar, O2Ar, and O2Xe dimers studied by Coulomb explosion imaging.
AB  - We use intense femtosecond laser pulses to multiply ionize and directly image the
      structures of N(2)Ar, O(2)Ar, and O(2)Xe dimers by coincidently measuring the
      momenta of the fragment ions. All these dimers are found to have an equilibrium T
      shaped structure in which the bond of the diatomic molecule is perpendicular to
      the dimer axis. The equilibrium distance between the rare-gas atom and the center
      of-mass of the diatomic molecule is estimated to be R(N2-Ar) ~ 3.86 A, R(O2-Ar) ~
      3.65 A, and R(O2-Xe) ~ 4.07 A, respectively. For the T-shaped N(2)Ar dimer, both
      sequential and direct triple-ionization-induced three-body breakups are observed.
      In contrast to N(2)Ar dimer, other structures are found to coexist with the
      dominating T-shaped one for O(2)Ar and O(2)Xe.

PMID- 22979861
TI  - Electromagnetically induced transparency in a Lambda-type molecular system with
      permanent dipole moments revisited.
AB  - Electromagnetically  induced transparency (EIT) in a molecular three-level Lambda
      system with permanent dipole moments and undergoing m- and n-photon transitions
      by pump and probe lasers is investigated. Analytical expressions are derived for
      probe absorption spectrum and dispersion for a medium of stationary as well as
      thermal molecules. Contrary to the earlier study by Zhou et al. [J. Chem. Phys.
      131, 034105 (2009)], we observe no amplification in 2 + 2 photon process when the
      sign of the difference of the permanent moments of the excited and the ground
      levels is reversed. Reasons for these contrasting observations are discussed. Our
      study shows that the permanent moments essentially damp the laser-molecule Rabi
      frequency to result in narrower EIT line width and larger group velocity index.
      These effects are further enhanced when the order of the multi-photon process is
      increased. The importance of the virtual mechanism is discussed by considering
      the special case of 2 + 1 photon EIT.

PMID- 22979863
TI  - A new four-dimensional ab initio potential energy surface for N2O-He and
      vibrational band origin shifts for the N2O-He(N) clusters with N = 1-40.
AB  - A new four-dimensional ab initio potential energy surface for N(2)O-He is
      constructed at the CCSD(T) level with an aug-cc-pVQZ basis set together with bond
      functions. The vibrational coordinates Q(1) and Q(3) of N(2)O are explicitly
      included, due to the strong coupling between the symmetric and asymmetric
      stretches of N(2)O. A global potential energy surface is obtained by fitting the
      original potential points to a four-dimensional Morse/long range (MLR) analytical
      form. In the fitting, the ab initio noise in the long range region of the
      potential is smoothed over by theoretically fixed long range parameters. Two
      dimensional intermolecular potentials for both the ground and the excited
      upsilon(3) states of N(2)O are then constructed by vibrationally averaging the
      four-dimensional potential. Based on the two-dimensional potentials, we use the
      path integral Monte Carlo algorithm to calculate the vibrational band origin
      shifts for the N(2)O-He(N) clusters using a first order perturbation theory
      estimate. The calculated shifts agree reasonably well with the experimental
      values and reproduce the evolution tendency from dimer to large clusters.

PMID- 22979862
TI  - Alternating-gradient focusing of the benzonitrile-argon van der Waals complex.
AB  - We report on the focusing and guiding of the van der Waals complex formed between
      benzonitrile molecules (C(6)H(5)CN) and argon atoms in a cold molecular beam
      using an ac electric quadrupole guide. The distribution of quantum states in the
      guided beam is non-thermal, because the transmission efficiency depends on the
      state-dependent effective dipole moment in the applied electric fields. At a
      specific ac frequency, however, the excitation spectrum can be described by a
      thermal distribution at a rotational temperature of 0.8 K. From the observed
      transmission characteristics and a combination of trajectory and Stark-energy
      calculations we conclude that the permanent electric dipole moment of
      benzonitrile remains unchanged upon the attachment of the argon atom to within +/
      5%. By exploiting the different dipole-moment-to-mass ([micro sign]/m) ratios of
      the complex and the benzonitrile monomer, transmission can be selectively
      suppressed for or, in the limit of 0 K rotational temperature, restricted to the
      complex.

PMID- 22979864
TI  - Zero kinetic energy photoelectron spectroscopy of tryptamine and the dissociation
      pathway of the singly hydrated cation cluster.
AB  - The relative ionization energies of tryptamine conformations are determined by
      zero kinetic energy photoelectron spectroscopy and photoionization efficiency
      measurements. The relative cationic conformational stabilities are compared to
      the published results for the neutral molecule. In the cation, the interaction
      strength changes significantly between amino group and either the phenyl or the
      pyrrole moiety of the indole chromophore where most of the positive charge is
      located, leading to different conformational structures and relative conformer
      energies in the cation. In particular, the measured adiabatic ionization
      potential of isomer B is 60,928 +/- 5 cm(-1), at least 400 cm(-1) higher than any
      of the 6 other tryptamine isomers which all have ionization potentials within 200
      cm(-1) of each other. In addition to the monomer, measurements were made on the A
      conformer of the tryptamine(+)-H(2)O complex including the ionization threshold
      and cation dissociation energy measured using a threshold photoionization
      fragmentation method. The water cluster exhibits an unexpectedly high ionization
      potential of 60,307 +/- 100 cm(-1), close to the conformer A monomer of 60 320 +/
      100 cm(-1). It also exhibits surprisingly low dissociation energy of 1750 +/-
      150 cm(-1) compared to other H-bonding involved cation-H(2)O complexes which are
      typically several thousands of wavenumbers higher. Quantum chemical calculations
      indicate that upon ionization the structure of the parent molecule in the water
      complex remains mostly unchanged due to the rigid intermolecular double hydrogen
      bonded water molecule bridging the monomer backbone and its side chain thus
      leading to the high ionization potential in the water cluster. The surprisingly
      low dissociation energy measured in the cationic water complex is attributed to
      the formation of a much more stable structural isomer H(+) in the exit channel.

PMID- 22979865
TI  - Terahertz and far-infrared synchrotron spectroscopy and global modeling of methyl
      mercaptan, CH3(32)SH.
AB  - In this work, terahertz and Fourier transform far-infrared (FTFIR) synchrotron
      spectra of methyl mercaptan, CH(3)SH, have been investigated in order to provide
      new laboratory information for enhanced observations of this species in
      interstellar molecular clouds and star-forming regions. Like its methanol cousin,
      methyl mercaptan has particularly rich spectra associated with its large
      amplitude internal rotation that extend throughout the THz and FIR regions. We
      have recorded new spectra for CH(3)SH from 1.1-1.5 and 1.790-1.808 THz at the
      University of Cologne as well as high-resolution FTFIR synchrotron spectra from
      50-550 cm(-1) at 0.001 cm(-1) resolution on the far-IR beam-line at the Canadian
      Light Source. Assignments are reported for rotational quantum numbers up to J ~
      40 and K ~ 15, and torsional states up to v(t) = 2 for the THz measurements and
      v(t) = 3 for the FTFIR observations. The THz and FTFIR measurements together with
      literature results have been combined in a global analysis of a dataset
      comprising a total of 1725 microwave and THz frequencies together with ~18000
      FTFIR transitions, ranging up to v(t) = 2 and J(max) = 30 for MW/THz and 40 for
      FTFIR. The global fit employs 78 torsion-rotation parameters and has achieved a
      weighted standard deviation of ~1.1. A prediction list (v(t) <= 2, J <= 45 and K
      <= 20) has been generated from the model giving essentially complete coverage of
      observable CH(3)(32)SH transitions within the bandwidths of major new
      astronomical facilities such as HIFI (Heterodyne Instrument for the Far Infrared)
      on the Herschel Space Observatory, ALMA (Atacama Large Millimeter Array), SOFIA
      (Stratospheric Observatory For Infrared Astronomy) and APEX (Atacama Pathfinder
      Experiment) to close to spectroscopic accuracy.

PMID- 22979866
TI  - Thermochemistry of radicals formed by hydrogen abstraction from 1-butanol, 2
      methyl-1-propanol, and butanal.
AB  - We calculate the standard state entropy, heat capacity, enthalpy, and Gibbs free
      energy for 13 radicals important for the combustion chemistry of biofuels. These
      thermochemical quantities are calculated from recently proposed methods for
      calculating partition functions of complex molecules by taking into account their
      multiple conformational structures and torsional anharmonicity. The radicals
      considered in this study are those obtained by hydrogen abstraction from 1
      butanol, 2-methyl-1-propanol, and butanal. Electronic structure calculations for
      all conformers of the radicals were carried out using both density functional
      theory and explicitly correlated coupled cluster theory with quasipertubative
      inclusion of connected triple excitations. The heat capacity and entropy results
      are compared with sparsely available group additivity data, and trends in
      enthalpy and free energy as a function of radical center are discussed for the
      isomeric radicals.

PMID- 22979867
TI  - Assessment of the accuracy the experimental energies of the 1P(o) 1s(2)2s6p and
      1s(2)2s7p states of 9Be based on variational calculations with explicitly
      correlated Gaussians.
AB  - Benchmark variational calculations are performed for the six lowest states of the
      (1)P(o) 1s(2)2snp state series of the (9)Be atom. The wave functions of the
      states are expanded in terms of all-particle, explicitly correlated Gaussian
      basis functions and the effect of the finite nuclear mass is directly included in
      the calculations. The exponential parameters of the Gaussians are variationally
      optimized using the analytical energy gradient determined with respect to those
      parameters. Besides providing reference non-relativistic energies for the
      considered states, the calculations also allow to assess the accuracy of the
      experimental energies of the (1)P(o) 1s(2)2s6p and 1s(2)2s7p states and suggest
      their refinement.

PMID- 22979868
TI  - Single file and normal dual mode diffusion in highly confined hard sphere
      mixtures under flow.
AB  - We use Monte Carlo simulations to study the dual-mode diffusion regime of binary
      and tertiary mixtures of hard spheres confined in narrow cylindrical pores under
      the influence of an imposed flow. The flow is introduced to the dynamics by
      adding a small bias directed along the long axis of the pore to the random
      displacement of each Monte Carlo move. As a result, the motion of the particles
      in all the components is dominated by a drift velocity that causes the mean
      squared displacements to increase quadratically in the long time limit. However,
      an analysis of the mean squared displacements at intermediate time scales shows
      that components of the mixture above and below their passing thresholds still
      exhibit behaviors consistent with normal and single-file diffusion, respectively.
      The difference between the mean squared displacements of the various components
      is shown to go though a maximum, suggesting there may be an optimal pore diameter
      for the separation of mixtures exhibiting dual-mode diffusion.

PMID- 22979869
TI  - Effects of 2 nm size added heterogeneity on non-exponential dielectric response,
      and the dynamic heterogeneity view of molecular liquids.
AB  - To investigate how non-exponential response could vary under different
      conditions, we studied the effects of adding 2 nm size polyhedral oligomeric
      silsesquioxane (POSS) to diglycidyl ether of bisphenol-A, whose molecules have
      the same terminal (epoxide) dipoles as the tentacle-like side chains attached to
      the silsesquioxane core of the POSS molecule. Dielectric relaxation spectra show
      that, on initial addition, the POSS nano-heterogeneity decreases the non
      exponential response parameter beta, which is consistent with the dynamic
      heterogeneity view, but it also decreases the relaxation time tau(m), which is
      inconsistent with that view. The variations in beta and tau(m) with the
      composition have a thermal equivalence. Despite the lack of translational
      diffusion required for dynamic heterogeneity, plastic crystals show non
      exponential response and non-Arrhenius dynamics. Measurements of beta and tau(m)
      seem more appropriate than using probe molecules or modeling nonlinear response
      data as a sum of linear responses for testing the dynamic heterogeneity view.
      Data on molecular liquid mixtures is not generally consistent with this view, and
      adding a solute does not always decrease beta. Studies of mixtures of different
      size rigid molecules with identical dipolar groups, including polymers, may be
      useful for comparing the relative effects of temperature and molecular size on
      beta and tau(m).

PMID- 22979870
TI  - Hexatic phase and water-like anomalies in a two-dimensional fluid of particles
      with a weakly softened core.
AB  - We study a two-dimensional fluid of particles interacting through a spherically
      symmetric and marginally soft two-body repulsion. This model can exist in three
      different crystal phases, one of them with square symmetry and the other two
      triangular. We show that, while the triangular solids first melt into a hexatic
      fluid, the square solid is directly transformed on heating into an isotropic
      fluid through a first-order transition, with no intermediate tetratic phase. In
      the low-pressure triangular and square crystals, melting is reentrant provided
      the temperature is not too low, but without the necessity of two competing
      nearest-neighbor distances over a range of pressures. A whole spectrum of water
      like fluid anomalies completes the picture for this model potential.

PMID- 22979871
TI  - The acoustic velocity, refractive index, and equation of state of liquid ammonia
      dihydrate under high pressure and high temperature.
AB  - High-pressure and high-temperature Brillouin scattering studies have been
      performed on liquid of composition corresponding to the ammonia dihydrate
      stoichiometry (NH(3).2H(2)O) in a diamond anvil cell. Using the measured
      Brillouin frequency shifts from 180 degrees  back- and 60 degrees  platelet
      scattering geometries, the acoustic velocity, refractive index, density, and
      adiabatic bulk modulus have been determined under pressure up to freezing point
      along the 296, 338, 376, and 407 K isotherms. Along these four isotherms, the
      acoustic velocities increase smoothly with increasing pressure but decrease with
      the increased temperature. However, the pressure dependence of the refractive
      indexes on the four isotherms exhibits a change in slope around 1.5 GPa. The bulk
      modulus increases linearly with pressure and its slope, dB/dP, decreases from
      6.83 at 296 K to 4.41 at 407 K. These new datasets improve our understanding of
      the pressure- and temperature-induced molecular structure changes in the ammonia
      water binary system.

PMID- 22979872
TI  - High-density amorphous ice: a path-integral simulation.
AB  - Structural and thermodynamic properties of high-density amorphous (HDA) ice have
      been studied by path-integral molecular dynamics simulations in the isothermal
      isobaric ensemble. Interatomic interactions were modeled by using the effective q
      TIP4P/F potential for flexible water. Quantum nuclear motion is found to affect
      several observable properties of the amorphous solid. At low temperature (T = 50
      K) the molar volume of HDA ice is found to increase by 6%, and the intramolecular
      O-H distance rises by 1.4% due to quantum motion. Peaks in the radial
      distribution function of HDA ice are broadened with respect to their classical
      expectancy. The bulk modulus, B, is found to rise linearly with the pressure,
      with a slope ?B/?P = 7.1. Our results are compared with those derived earlier
      from classical and path-integral simulations of HDA ice. We discuss similarities
      and discrepancies with those earlier simulations.

PMID- 22979873
TI  - Analysis of the basis set superposition error in molecular dynamics of hydrogen
      bonded liquids: application to methanol.
AB  - An efficient protocol is presented to compensate for the basis set superposition
      error (BSSE) in DFT molecular dynamics (MD) simulations using localized Gaussian
      basis sets. We propose a classical correction term that can be added a posteriori
      to account for BSSE. It is tested to what extension this term will improve radial
      distribution functions (RDFs). The proposed term is pairwise between certain
      atoms in different molecules and was calibrated by fitting reference BSSE data
      points computed with the counterpoise method. It is verified that the proposed
      exponential decaying functional form of the model is valid. This work focuses on
      hydrogen-bonded liquids, i.e., methanol, and more specific on the intermolecular
      hydrogen bond, but in principle the method is generally applicable on any type of
      interaction where BSSE is significant. We evaluated the relative importance of
      the Grimme-dispersion versus BSSE and found that they are of the same order of
      magnitude, but with an opposite sign. Upon introduction of the correction, the
      relevant RDFs, obtained from MD, have amplitudes equal to experiment.

PMID- 22979874
TI  - Calculation of the melting point of alkali halides by means of computer
      simulations.
AB  - In this paper, we study the liquid-solid coexistence of NaCl-type alkali halides,
      described by interaction potentials such as Tosi-Fumi (TF), Smith-Dang (SD), and
      Joung-Cheatham (JC), and compute their melting temperature (T(m)) at 1 bar via
      three independent routes: (1) liquid/solid direct coexistence, (2) free-energy
      calculations, and (3) Hamiltonian Gibbs-Duhem integration. The melting points
      obtained by the three routes are consistent with each other. The calculated T(m)
      of the Tosi-Fumi model of NaCl is in good agreement with the experimental value
      as well as with other numerical calculations. However, the other two models
      considered for NaCl, SD and JC, overestimate the melting temperature of NaCl by
      more than 200 K. We have also computed the melting temperature of other alkali
      halides using the Tosi-Fumi interaction potential and observed that the
      predictions are not always as close to the experimental values as they are for
      NaCl. It seems that there is still room for improvement in the area of force
      fields for alkaline halides, given that so far most models are still unable to
      describe a simple yet important property such as the melting point.

PMID- 22979876
TI  - Structure, compressibility factor, and dynamics of highly size-asymmetric binary
      hard-disk liquids.
AB  - By using event-driven molecular dynamics simulation, we investigate effects of
      varying the area fraction of the smaller component on structure, compressibility
      factor, and dynamics of the highly size-asymmetric binary hard-disk liquids. We
      find that the static pair correlations of the large disks are only weakly
      perturbed by adding small disks. The higher-order static correlations of the
      large disks, by contrast, can be strongly affected. Accordingly, the static
      correlation length deduced from the bond-orientation correlation functions first
      decreases significantly and then tends to reach a plateau as the area fraction of
      the small disks increases. The compressibility factor of the system first
      decreases and then increases upon increasing the area fraction of the small disks
      and separating different contributions to it allows to rationalize this non
      monotonic phenomenon. Furthermore, adding small disks can influence dynamics of
      the system in quantitative and qualitative ways. For the large disks, the
      structural relaxation time increases monotonically with increasing the area
      fraction of the small disks at low and moderate area fractions of the large
      disks. In particular, "reentrant" behavior appears at sufficiently high area
      fractions of the large disks, strongly resembling the reentrant glass transition
      in short-ranged attractive colloids and the inverted glass transition in binary
      hard spheres with large size disparity. By tuning the area fraction of the small
      disks, relaxation process for the small disks shows concave-to-convex crossover
      and logarithmic decay behavior, as found in other binary mixtures with large size
      disparity. Moreover, diffusion of both species is suppressed by adding small
      disks. Long-time diffusion for the small disks shows power-law-like behavior at
      sufficiently high area fractions of the small disks, which implies precursors of
      a glass transition for the large disks and a localization transition for the
      small disks. Therefore, our results demonstrate the generic dynamic features in
      highly size-asymmetric binary mixtures.

PMID- 22979875
TI  - Cluster formation restricts dynamic nuclear polarization of xenon in solid
      mixtures.
AB  - During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, (129)Xe nuclear
      magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical
      solid mixture exhibit a single peak, broadened by (1)H neighbors. A second peak
      appears upon annealing for several hours at 125 K. Its characteristic width and
      chemical shift indicate the presence of spontaneously formed pure Xe clusters.
      Microwave irradiation at the appropriate frequencies can bring both peaks to
      either positive or negative polarization. The peculiar time evolution of (129)Xe
      polarization in pure Xe clusters during DNP can be modelled as an interplay of
      spin diffusion and T(1) relaxation. Our simple spherical-cluster model offers a
      sensitive tool to evaluate major DNP parameters in situ, revealing a severe spin
      diffusion bottleneck at the cluster boundaries and a significant sample
      overheating due to microwave irradiation. Subsequent DNP system modifications
      designed to reduce the overheating resulted in four-fold increase of (129)Xe
      polarization, from 5.3% to 21%.

PMID- 22979877
TI  - Computer simulation study of collective dynamics in the glass former
      Ca(NO3)2.4H2O.
AB  - Time correlation functions of current fluctuations were calculated by molecular
      dynamics (MD) simulations in order to investigate sound waves of high wavevectors
      in the glass-forming liquid Ca(NO(3))(2).4H(2)O. Dispersion curves, omega(k),
      were obtained for longitudinal (LA) and transverse acoustic (TA) modes, and also
      for longitudinal optic (LO) modes. Spectra of LA modes calculated by MD
      simulations were modeled by a viscoelastic model within the memory function
      framework. The viscoelastic model is used to rationalize the change of slope
      taking place at k ~ 0.3 A(-1) in the omega(k) curve of acoustic modes. For still
      larger wavevectors, mixing of acoustic and optic modes is observed. Partial time
      correlation functions of longitudinal mass currents were calculated separately
      for the ions and the water molecules. The wavevector dependence of excitation
      energies of the corresponding partial LA modes indicates the coexistence of a
      relatively stiff subsystem made of cations and anions, and a softer subsystem
      made of water molecules.

PMID- 22979878
TI  - Relationship between mesoscale dynamics and shear relaxation of ionic liquids
      with long alkyl chain.
AB  - The shear relaxation spectra of three imidazolium-based ionic liquids, 1-methyl-3
      octylimidazolium chloride ([C(8)mim][Cl]), 1-methyl-3-octylimidazolium
      hexafluorophosphate ([C(8)mim][PF(6)]), and 1-dodecyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide ([C(12)mim][TFSA]) were measured and compared
      with the intermediate scattering functions determined with neutron spin echo
      (NSE) spectroscopy. The shear relaxation is slower than that predicted from the
      relaxation of the main peak of the structure factor that is common to other
      molecular liquids, whereas it is faster than that from the relaxation of the pre
      peak, that corresponds to the correlation length of about 10 nm specific to ionic
      liquids with an intermediately long alkyl chain. The role of the pre-peak
      structure in the mechanism of shear viscosity of ionic liquids is discussed based
      on the comparison between NSE and shear relaxations.

PMID- 22979879
TI  - Molecular dynamics simulation of the effect of bond flexibility on the transport
      properties of water.
AB  - Molecular dynamics simulations for the shear viscosity and self-diffusion
      coefficient of pure water were performed to investigate the effect of including
      intramolecular degrees of freedom in simple point charge (SPC) models over a wide
      range of state points. Results are reported for the flexible SPC/Fw model, its
      rigid SPC counterpart, and the widely used SPC/E model. The simulations covered
      the liquid phase from 277.15 to 363.15 K and the supercritical phase at 673.15 K
      and pressures up to 200 MPa. The flexibility exhibited by the SPC/Fw model
      results in slowing down of the dynamics. That is, it results in higher shear
      viscosities and lower diffusion coefficients than can be obtained from the rigid
      model, resulting in better agreement with experimental data. Significantly, the
      SPC/Fw model can be used to adequately predict the diffusion coefficients at
      ambient and supercritical temperatures over a wide range of pressures.

PMID- 22979880
TI  - Nucleation mechanism for vapor-to-liquid transition from substrates with
      nanoscale pores opened at one end.
AB  - In this work, we study the nucleation mechanism of vapor-to-liquid phase
      transition from rough substrates, which are modeled as flat substrates decorated
      with square nanopores with one open end. Our calculations in a constrained
      lattice density functional theory shows that the presence of nanopores results in
      an intermediate state, either metastable or unstable, which divides the whole
      nucleation process into two sequential sub-processes, i.e., pore filling and
      phase transition outside the pores. Therefore, the nucleation mechanism was found
      to be one-step (with unstable intermediate states) or two-step (with metastable
      intermediate states), depending on the fluid-solid interaction, chemical
      potential, and pore size. The constructed phase diagram of nucleation mechanism
      shows that there exist six different nucleation mechanisms. In addition, our
      calculations show that the presence of nanopores on a rough substrate may change
      the morphology of critical nuclei from their counterpart on a smooth substrate.

PMID- 22979881
TI  - Quantum efficiency of intermediate-band solar cells based on non-compensated n-p
      codoped TiO2.
AB  - As an appealing concept for developing next-generation solar cells, intermediate
      band solar cells (IBSCs) promise to drastically increase the quantum efficiency
      of photovoltaic conversion. Yet to date, a standing challenge lies in the lack of
      materials suitable for developing IBSCs. Recently, a new doping approach, termed
      non-compensated n-p codoping, has been proposed to construct intermediate bands
      (IBs) in the intrinsic energy band gaps of oxide semiconductors such as TiO(2).
      We explore theoretically the optimal quantum efficiency of IBSCs based on non
      compensated n-p codoped TiO(2) under two different design schemes. The first
      preserves the ideal condition that no electrical current be extracted from the
      IB. The corresponding maximum quantum efficiency for the codoped TiO(2) can reach
      52.7%. In the second scheme, current is also extracted from the IB resulting in a
      further enhancement in the maximum efficiency to 56.7%. Our findings also relax
      the stringent requirement that the IB location be close to the optimum value,
      making it more feasible to realize IBSCs with high quantum efficiencies.

PMID- 22979882
TI  - Surface adsorption of colloidal brushes at good solvents conditions.
AB  - Monte Carlo simulations are presented for a minimal model of one spherical
      colloidal particle as it interacts with one attractive flat substrate. The
      colloidal particle is decorated by either 6 or 14 grafted polymer chains. The
      chains are always rather short, with their radius of gyration, estimated at
      infinite dilution in good solvent conditions, never larger than the spherical
      colloid diameter. Although all simulations are conducted under "good-solvent"
      conditions for the grafted polymer chains, we find that small changes in the
      polymer segment-polymer segment energetic interaction parameter can lead to
      significantly different scenarios. When the Lennard-Jones attraction is weak,
      0.12 k(B)T, increasing the polymer length decreases the likelihood of colloidal
      adsorption, as expected. On the contrary, when the attraction is 0.18 k(B)T,
      increasing the length of the grafted polymer chains promotes the adsorption of
      the colloidal brush onto the surface. When the Lennard-Jones energetic parameter
      that describes polymer segment-polymer segment interactions is 0.15 k(B)T, as the
      length of the grafted polymer chains increases the probability of colloidal
      adsorption decreases to a minimum, and then increases. The results, explained in
      terms of a competition between entropic (due to the reduction in degrees of
      freedom available to the grafted polymer chains upon colloidal brush adsorption)
      and enthalpic driving forces (due to favorable colloid-surface and polymer
      segment-surface interactions), could be useful for controlling the circulation
      lifetime of liposomes within the blood stream, and optimizing solar energy
      harvesting by depositing colloidal particles on solid surfaces.

PMID- 22979883
TI  - Anisotropy in the dielectric spectrum of hydration water and its relation to
      water dynamics.
AB  - Proteins, molecules, and macromolecular assemblies in water are surrounded by a
      nanometer-sized hydration layer with properties very different from bulk water.
      Here, we use classical molecular dynamics simulations to study the dielectric
      response of hydration water next to hydrophobic and hydrophilic planar surfaces.
      We find the interfacial dielectric absorption of water to be strongly
      anisotropic: compared to bulk water, which shows a broad dielectric absorption
      maximum around 15 GHz in the imaginary part of the dielectric function, the
      absorption for electric fields parallel to the surface is of similar strength and
      shows a slight redshift, while for perpendicular electric fields it is strongly
      attenuated and blueshifted. This anisotropy is generic for hydrophobic and
      hydrophilic surfaces. From our spatially resolved dielectric functions and a
      modified Maxwell-Garnett theory that accounts for anisotropic hydration layers
      around spherical particles, the dielectric absorption of solutions of organic
      molecules and micelles is derived to exhibit the experimentally known attenuation
      in combination with a redshift. These two features are traced back to the subtle
      interplay of interfacial depolarization effects and the dielectric anisotropy in
      the hydration layer. By a detailed analysis of the individual water molecule
      dynamics the perpendicular blueshift is shown not to be linked to accelerated
      water reorientation, but rather to dielectric boundary effects. Carefully
      conducted angularly resolved experiments at planar aqueous interfaces will be
      able to resolve this dielectric anisotropy and thus to confirm the subtle
      connection between spectral absorption features and the molecular water dynamics
      in hydration layers.

PMID- 22979884
TI  - Effect of nanoparticle polydispersity on the self-assembly of polymer tethered
      nanospheres.
AB  - Recent simulations predict that aggregating nanospheres functionalized with
      polymer "tethers" can self-assemble to form a cylinder, perforated lamellae,
      lamellae, and even the double gyroid phase, which are phases also seen in block
      copolymer and surfactant systems. Nanoparticle size polydispersity is likely to
      be a characteristic of these systems. If too high, polydispersity may destabilize
      a phase. Using multiple thermodynamic paths to explore the phase diagram as a
      function of temperature and polydispersity, we explore the effect of nanosphere
      size polydispersity on the phase diagram. We show that in the portions of the
      phase diagram characterized by an icosahedral local nanoparticle packing motif, a
      low amount of polydispersity lowers the energy and a large amount of
      polydispersity raises the energy of the system by disrupting the icosahedral
      packing. In general, regions of the phase diagram characterized by liquid-like
      icosahedral packing have high terminal polydispersities from 15% to more than
      30%. In the regions of the phase diagram characterized by crystalline local
      packing, polydispersity raises the energy of the system and induces a phase
      transition from crystalline to liquid-like ordering within the nanosphere rich
      regions of the microphase. We find the bilayer crystalline lamellae phase has a
      terminal polydispersity of 6%, but may still be partially crystalline up to 12%.

PMID- 22979885
TI  - Electrostatic correlations in inhomogeneous charged fluids beyond loop expansion.
AB  - Electrostatic correlation effects in inhomogeneous symmetric electrolytes are
      investigated within a previously developed electrostatic self-consistent theory
      [R. R. Netz and H. Orland, Eur. Phys. J. E 11, 301 (2003)]. To this aim, we
      introduce two computational approaches that allow to solve the self-consistent
      equations beyond the loop expansion. The first method is based on a perturbative
      Green's function technique, and the second one is an extension of a previously
      introduced semiclassical approximation for single dielectric interfaces to the
      case of slit nanopores. Both approaches can handle the case of dielectrically
      discontinuous boundaries where the one-loop theory is known to fail. By comparing
      the theoretical results obtained from these schemes with the results of the Monte
      Carlo simulations that we ran for ions at neutral single dielectric interfaces,
      we first show that the weak coupling Debye-Huckel theory remains quantitatively
      accurate up to the bulk ion density rho(b) ? 0.01 M, whereas the self-consistent
      theory exhibits a good quantitative accuracy up to rho(b) ? 0.2 M, thus improving
      the accuracy of the Debye-Huckel theory by one order of magnitude in ionic
      strength. Furthermore, we compare the predictions of the self-consistent theory
      with previous Monte Carlo simulation data for charged dielectric interfaces and
      show that the proposed approaches can also accurately handle the correlation
      effects induced by the surface charge in a parameter regime where the mean-field
      result significantly deviates from the Monte Carlo data. Then, we derive from the
      perturbative self-consistent scheme the one-loop theory of asymmetrically
      partitioned salt systems around a dielectrically homogeneous charged surface. It
      is shown that correlation effects originate in these systems from a competition
      between the salt screening loss at the interface driving the ions to the bulk
      region, and the interfacial counterion screening excess attracting them towards
      the surface. This competition can be quantified in terms of the characteristic
      surface charge sigma(s)*=?(2rho(b)/(pil(B)), where l(B) = 7 A is the Bjerrum
      length. In the case of weak surface charges sigma(s)?sigma(s)* where counterions
      form a diffuse layer, the interfacial salt screening loss is the dominant effect.
      As a result, correlation effects decrease the mean-field density of both coions
      and counterions. With an increase of the surface charge towards sigma(s)*, the
      surface-attractive counterion screening excess starts to dominate, and
      correlation effects amplify in this regime the mean-field density of both type of
      ions. However, in the regime sigma(s)>sigma(s)*, the same counterion screening
      excess also results in a significant decrease of the electrostatic mean-field
      potential. This reduces in turn the mean-field counterion density far from the
      charged surface. We also show that for sigma(s)?sigma(s)*, electrostatic
      correlations result in a charge inversion effect. However, the electrostatic
      coupling regime where this phenomenon takes place should be verified with Monte
      Carlo simulations since this parameter regime is located beyond the validity
      range of the one-loop theory.

PMID- 22979886
TI  - Nonequilibrium polymer chains induced by conformational transitions in densely
      interfacial layers.
AB  - Nonequilibrium poly(N-isopropylacrylamide) (PNIPAM) chains are generated by
      temperature-induced conformational transitions in the densely interfacial PNIPAM
      layer at high adsorbed amounts in aqueous solution. The interleaving chains relax
      in a spatially heterogeneous space of adsorbed layer which is filled with the
      domains via the hydrogen bonding and hydrophobic interactions. The relaxation
      dynamics of interleaving chains is changed from the weekly stretched exponential
      behaviour at the lower adsorbed amount to the strongly stretched exponential
      behaviour at the higher adsorbed amount. The kinetic constraints for the
      relaxation dynamics depend on the segment density of the adsorbed layer which is
      controlled by the temperature. The stretched exponential relaxation is related to
      an ensemble of relaxations confined in the domains with different physical
      origins for the heterogeneous dynamics. The range of energy barriers for the
      relaxation is estimated from the stretched exponent based on the random first
      order transition theory.

PMID- 22979887
TI  - The interplay of the polyelectrolyte-surface electrostatic and non-electrostatic
      interactions in the polyelectrolytes adsorption onto two charged objects--a self
      consistent field study.
AB  - The continuum self-consistent field (SCF) theory is applied to the study of the
      adsorption of flexible polyelectrolytes (PEs) onto the surfaces of two parallel
      and infinitely long charged columns, taking into account the short-range monomer
      surface non-Coulombic interaction. Due to the complex interplay between the
      electrostatic and surface interactions, very interesting PE adsorption behaviors
      in terms of the degree of charge compensation and the bridging chain conformation
      are found from the numerical solution of the SCF equations. The screening
      enhanced salt effect and the permanent adsorption of PEs, irrespectively of the
      salt concentration, emerge in the presence of the monomer-surface non
      electrostatic interaction. The numerical results reveal that, for relatively weak
      monomer-surface interactions, the degree of charge compensation decreases with
      increasing monomer-surface interaction. Numerical result shows that, for the
      strength of monomer-surface interaction above the desorption-adsorption critical
      value and in a salt-free solution, the total amount of the adsorbed PE chains is
      linearly proportional to the surface charge density in the high PE charge
      fraction regime.

PMID- 22979888
TI  - Charge renormalization of bilayer elastic properties.
AB  - By combining molecular dynamics simulations and analytical arguments, we
      investigate the elastic properties of charged lipid bilayers. We show that
      electrostatic interactions between the head groups can lead to solidification of
      the lipid bilayer that would otherwise be in a liquid state if the charges were
      absent. All elastic parameters of the bilayer such as the bending rigidity kappa
      and the two-dimensional bulk modulus lambda and Young's modulus Y are found to
      depend on the values of the charges assigned to the lipid head groups. To extract
      kappa and lambda, we fit the molecular dynamics data to a standard elastic model
      for lipid bilayers. Moreover, we analytically obtain the dependence of the Young
      modulus Y on the relative strengths of electrostatic and van der Waals
      interactions in the zero temperature limit.

PMID- 22979889
TI  - Element-specific study of local segmental dynamics of polyethylene terephthalate
      upon physical aging.
AB  - Time-dependent relaxation processes upon physical aging below the glass
      transition temperature have been studied in polyethylene terephthalate by high
      precision dilatometry (DLT), differential scanning calorimetry (DSC), and element
      specific positron and positronium (Ps) annihilation spectroscopy. The macroscopic
      volume change observed by DLT can be described by the Kohlrausch-Williams-Watts
      decay function, whereas changes in the relaxation enthalpies evaluated by DSC and
      free volumes probed by positron and Ps annihilation spectroscopy are reproduced
      by two superimposed exponentials. The multi-method approach reveals three kinds
      of relaxation processes with characteristic relaxation times: (a) fast Arrhenius
      type beta relaxation involving the instantaneous local segmental densification
      along with the exclusion of oxygen atoms from free volumes, (b) macroscopically
      observable non-Arrhenius-type alpha relaxation originated from a distribution of
      relaxation times due to the heterogeneous dynamics of solid-state- and liquid
      state-like local segments, and (c) extremely slow Arrhenius-type alpha relaxation
      as the consequence of a uniform relaxation time solely due to the thermal
      dependence of nanometer-scale solid-state-like local segments.

PMID- 22979890
TI  - Topological classification of Brownian orbits.
AB  - This paper presents the exact formula for the bivariate probability distribution
      function of a Brownian particle as a function of its position and velocity, whose
      orbit makes a specified number of turns around an infinite straight line. In the
      limit of large friction constant, the solution reduces to the well-known results
      for random Wiener paths. Topological entanglements of stiff polymers are
      discussed on the basis of this solution. The method to find the solution is
      applied to the velocity space of a Brownian motion, and the probability to find a
      closed path with a specified winding number is obtained. Hence, closed two
      dimensional Brownian orbits are classified into regular homotopy classes, whose
      statistical weight is derived as a function of the total length and the friction
      constant.

PMID- 22979891
TI  - Dynamic mechanisms of generation of oscillatory cluster patterns in a globally
      coupled chemical system.
AB  - We use simulations and dynamical systems tools to investigate the mechanisms of
      generation of phase-locked and localized oscillatory cluster patterns in a
      globally coupled Oregonator model where the activator receives global feedback
      from the inhibitor, mimicking experimental results observed in the photosensitive
      Belousov-Zhabotinsky reaction. A homogeneous two-cluster system (two clusters
      with equal cluster size) displays antiphase patterns. Heterogenous two-cluster
      systems (two clusters with different sizes) display both phase-locked and
      localized patterns depending on the parameter values. In a localized pattern the
      oscillation amplitude of the largest cluster is roughly an order of magnitude
      smaller than the oscillation amplitude of the smaller cluster, reflecting the
      effect of self-inhibition exerted by the global feedback term. The transition
      from phase-locked to localized cluster patterns occurs as the intensity of global
      feedback increases. Three qualitatively different basic mechanisms, described
      previously for a globally coupled FitzHugh-Nagumo model, are involved in the
      generation of the observed patterns. The swing-and-release mechanism is related
      to the canard phenomenon (canard explosion of limit cycles) in relaxation
      oscillators. The hold-and-release and hold-and-escape mechanisms are related to
      the release and escape mechanisms in synaptically connected neural models. The
      methods we use can be extended to the investigation of oscillatory chemical
      reactions with other types of non-local coupling.

PMID- 22979892
TI  - Wertheim's association theory applied to one site patchy colloids: beyond the
      single bonding condition.
AB  - We apply Wertheim's theory to develop an equation of state for one site patchy
      colloids where the patch can bond multiple times. We allow for the possibility of
      ring formation without the introduction of empirical parameters and show that for
      moderate patch coverage the infinite series of chain graphs is well represented
      by the first two terms. The theory is found to be in excellent agreement with new
      NVT and NPT Monte Carlo simulations. The approach described here can easily be
      converted to the form of a density functional theory to describe inhomogeneous
      patchy colloid systems.

PMID- 22979893
TI  - Electrostatic interactions between Janus particles.
AB  - In this paper we study the electrostatic properties of "Janus" spheres with
      unequal charge densities on both hemispheres. We introduce a method to compare
      primitive-model Monte Carlo simulations of the ionic double layer with
      predictions of (mean-field) nonlinear Poisson-Boltzmann theory. We also derive
      practical Derjaguin Landau Verwey Overbeek (DLVO)-like expressions that describe
      the Janus-particle pair interactions by mean-field theory. Using a large set of
      parameters, we are able to probe the range of validity of the Poisson-Boltzmann
      approximation, and thus of DLVO-like theories, for such particles. For
      homogeneously charged spheres this range corresponds well to the range that was
      predicted by field-theoretical studies of homogeneously charged flat surfaces.
      Moreover, we find similar ranges for colloids with a Janus-type charge
      distribution. The techniques and parameters we introduce show promise for future
      studies of an even wider class of charged-patterned particles.

PMID- 22979894
TI  - Orientational interactions in block copolymer melts: self-consistent field
      theory.
AB  - We study the phase behavior of diblock copolymer melts with one block possessing
      orientation-dependent segmental interactions using self-consistent field theory.
      A generalized coarse-grained description is introduced based on the local (polar)
      orientational order parameter and K, an effective Frank elastic constant for
      orientational gradients. To explore the role played by orientational interactions
      in assembly thermodynamics, we apply the theory to two-dimensional melt
      morphologies for a range of K. As microphase segregation necessarily introduces
      splay deformations of the segment orientation, we find that increasing the
      stiffness K raises the critical chiN at the onset of microphase separation.
      Furthermore, we find that strong orientational interactions in one block give
      rise to highly asymmetric phase diagrams due to the large penalty for high-splay
      morphologies, such as the cylindrical phase. Finally, we analyze the costs of
      inter-segmental splay as well as the size dependence of domain spacing on K based
      on a strong-segregation picture of morphologies.

PMID- 22979895
TI  - Electron ionization and dissociation of aliphatic amino acids.
AB  - We present experimental and theoretical study of electron ionization and
      dissociative ionization to the gas phase amino acids valine, leucine, and
      isoleucine. A crossed electron/molecular beams technique equipped with quadrupole
      mass analyzer has been applied to measure mass spectra and ion efficiency curves
      for formation of particular ions. From experimental data the ionization energies
      of the molecules and the appearance energies of the fragment ions were
      determined. Ab initio calculations (Density Functional Theory and G3MP2 methods)
      were performed in order to calculate the fragmentation paths and interpret the
      experimental data. The experimental ionization energies of parent molecules
      [P](+) 8.91 +/- 0.05, 8.85 +/- 0.05, and 8.79 +/- 0.05 eV and G3MP2 ionization
      energies (adiabatic) of 8.89, 8.88, and 8.81 eV were determined for valine,
      leucine, and isoleucine, respectively, as well as the experimental and
      theoretical threshold energies for dissociative ionization channels. The
      comparison of experimental data with calculations resulted in identification of
      the ions as well as the neutral fragments formed in the dissociative reactions.
      Around 15 mass/charge ratio fragments were identified from the mass spectra by
      comparison of experimental appearance energies with calculated reaction
      enthalpies for particular dissociative reactions.

PMID- 22979896
TI  - Ab initio determination of coarse-grained interactions in double-stranded DNA.
AB  - We derive the coarse-grained interactions between DNA nucleotides from ab initio
      total-energy calculations based on density functional theory (DFT). The
      interactions take into account base and sequence specificity, and are decomposed
      into physically distinct contributions that include hydrogen bonding, stacking
      interactions, backbone, and backbone-base interactions. The interaction energies
      of each contribution are calculated from DFT for a wide range of configurations
      and are fitted by simple analytical expressions for use in the coarse-grained
      model, which reduces each nucleotide into two sites. This model is not derived
      from experimental data, yet it successfully reproduces the stable B-DNA structure
      and gives good predictions for the persistence length. It may be used to
      realistically probe dynamics of DNA strands in various environments at the MUs
      time scale and the MUm length scale.

PMID- 22979897
TI  - Lattice model simulations of the effects of the position of a peptide trigger
      segment on helix folding and dimerization.
AB  - The folding and dimerization of proteins is greatly facilitated by the presence
      of a trigger site, a segment of amino acids that has a higher propensity for
      forming alpha-helix structure as compared to the rest of the chain. In addition
      to the helical propensity of each chain, dimerization can also be facilitated by
      interhelical interactions such as saltbridges, and interfacial contacts of
      different strengths. In this work, we are interested in understanding the
      interplay of these interactions in a model peptide system. We investigate how
      these different interactions influence the kinetics of dimer formation and the
      stability of the fully formed dimer. We use lattice model computer simulations to
      investigate how the effectiveness of the trigger segment and its saltbridges
      depends on the location along the protein primary sequence. For different
      positions of the trigger segment, heat capacity and free energy of unfolded and
      folded configurations are calculated to study the thermodynamics of folding and
      dimerization. The kinetics of the process is investigated by calculating
      characteristic folding times. The thermodynamic and kinetic data from the
      simulations combine to show that the dimerization process of the model system is
      faster when the segment with high helical propensity is located near either end
      of the peptide, as compared to the middle of the chain. The dependence of the
      stability of the dimer on the trigger segment's position is also studied. The
      stability can play a role in the ability of the dimer to perform a biological
      function that involves partial unzipping. The results on folding and dimer
      stability provide important insights for designing proteins that involve trigger
      sites.

PMID- 22979900
TI  - Interim report: a randomized controlled trial comparing postoperative pain in
      single-incision laparoscopic cholecystectomy and conventional laparoscopic
      cholecystectomy.
AB  - INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) is increasingly
      practiced, but there have been no well-powered randomized trials investigating
      the technique. This non-inferiority trial aims to compare SILC with conventional
      four-port laparoscopic cholecystectomy (LC) with postoperative pain as the
      primary endpoint. METHODS: We aim to randomize 100 patients into equal arms of
      SILC or LC. Exclusion criteria were: (i) acute cholecystitis; (ii) an ASA score
      of 3 or above; (iii) bleeding disorders; or (iv) previous upper abdominal
      surgery. Patients and postoperative assessors were blinded to the procedure
      received. The site and severity of pain was compared based on the visual analogue
      scale at 4 hours, 24 hours and 14 days postoperatively; non-inferiority was
      assumed when the lower boundary of the 95% confidence interval of the difference
      was above -1, and superiority when P <= 0.05. RESULTS: We recruited 24 SILC and
      26 LC patients. There were no conversions to open cholecystectomy or from SILC to
      LC. SILC was non-inferior for pain at umbilical sites at rest and at extra
      umbilical sites at all times. At 24 hours postoperatively, SILC was associated
      with significantly less pain at extra-umbilical sites (rest: P = 0.002; movement:
      P = 0.004). There were no incidents of biliary injury or retained gallstones. Of
      the 24 SILC patients, 12.5% had postoperative complications (vomiting, mild fluid
      overload, wound infection) compared with 0% of LC patients (P = 0.110); all
      complications resolved with conservative management. Operating time, analgesic
      use, return to function, and overall satisfaction did not differ significantly
      between the two groups. CONCLUSION: SILC is associated with reduced pain and is
      feasible in routine surgical practice.

PMID- 22979901
TI  - Effects of population size on singing behavior of a rare duetting songbird.
AB  - Although the genetic and ecological effects of population declines in endangered
      species have been well studied, little is known of the social consequences.
      Changes in signaling behavior may result in disrupted communication and affect
      both reproductive and conflict-resolution activities. The North Island Kokako
      (Callaeas wilsoni) is an endangered, duetting (i.e., alternating, coordinated
      singing by mated pairs) songbird endemic to New Zealand temperate rain forests.
      Scattered populations (approximately 1500 individuals in 13 surviving and 11
      translocated populations) in isolated conservation areas of different sizes have
      been rescued from extirpation and are currently recovering. We examined key song
      attributes of the Kokako to assess whether population size or growth rate are
      related to song complexity, the reduction of which may compromise effective
      communication. We analyzed song repertoire size and phrase-type sharing (i.e.,
      Jaccard index of similarity), vocal performance (singing rates, song switching
      rates, and diversity of phrase types), and song syntactical characteristics
      (i.e., unpredictability in sequences of phrase types) in surviving and
      translocated populations (populations of approximately 19-250 territorial
      individuals). Population size was positively correlated with a population's song
      repertoire, song diversity, and switching of song phrase types and negatively
      correlated with shared phrase types and variation in syntactical structure of
      songs. Population growth rate correlated positively with pair repertoire size,
      population repertoire size, and singing rates during song bouts. As for solo
      singing species in fragmented landscapes, songs in the fragmented populations of
      Kokako appear to be undergoing microevolution as occurs in island colonization
      events. Our results suggest that vocal changes in small populations could affect
      population establishment and growth, particularly in multiple-source
      translocations. We believe measurement of vocal behavior could be used as a
      supplement to periodic population censuses to allow more frequent monitoring of
      population size.

PMID- 22979903
TI  - Mitochondrial outer membrane channels.

PMID- 22979904
TI  - Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory
      deficit in mice.
AB  - CONTEXT: Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and
      Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the
      treatment of inflammatory disorders and mental illness. OBJECTIVE: This study
      evaluated the antidementic effect of the methanol root extracts of C. mucronatum
      and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in
      mice. MATERIALS AND METHODS: The effect of C. mucronatum and C. thonningii (50
      200 mg/kg) administered orally for 3 days on memory impairments induced in mice
      by scopolamine was assessed in the passive avoidance and Morris water maze test
      and compared with that of tacrine (5 mg/kg, i.p.). The activities of
      acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain
      after the completion of behavioral studies. RESULTS: C. mucronatum and C.
      thonningii root extracts (50-200 mg/kg) reversed scopolamine-induced memory
      deficit with significant (p < 0.05) increase in transfer latency in passive
      avoidance test. Similarly, the extracts (200 mg/kg) ameliorated memory deficit as
      a result of significant (p < 0.001) decrease in escape latency and path length in
      Morris water maze test. The increased AChE activity induced by scopolamine was
      significantly (p < 0.05) inhibited by C. mucronatum and C. thonningii (100 and
      200 mg/kg) treatment which was similar to the effect of tacrine. Both extracts
      significantly (p < 0.05) attenuated scopolamine-induced increase in oxidative
      stress parameters as well as restoration of glutathione activity. DISCUSSION AND
      CONCLUSION: C. mucronatum and C. thonningii extracts possess significant
      anticholinesterase, antioxidant and antidementic properties, which may be useful
      in the management of Alzheimer's disease.

PMID- 22979905
TI  - The 50 Hz (10 mT) sinusoidal magnetic field: effects on stress-related behavior
      of rats.
AB  - PURPOSE: The purpose of this study was to investigate the behavioral changes
      induced by 50 Hz, 10 mT flux density Sinusoidal Magnetic Field (MF). MATERIAL AND
      METHODS: Seventy-six young adult male Wistar albino rats were used in the study.
      They were separated into two groups: control group (C) n=38; MF group n=38. C
      animals were left under the same conditions with the MF group for 21 days but
      with prevented or avoided exposure to MF. Anxiety and stress-related behavioral
      changes were investigated by elevated plus-maze and hole-board systems. Just
      before being tested in the maze, each animal was tested by means of the hole
      board method in order to separate the directed exploration behavior and
      locomotion activity changes from anxiety-related behavior. RESULTS: In the hole
      board system parameters there were no statistically significant differences
      between the two groups. There was a statistically significant difference between
      MF and C groups when the ratio of time spent on open arms to the total time spent
      on all arms was evaluated (0.12+/-0.08 and 0.34+/-0.18 respectively and p <0.01).
      CONCLUSION: Our results suggest that after 21 days, a continuous exposure to
      extremely low frequency of magnetic field (50 Hz, 10 mT) has no significant
      effect on activity and exploration activity but significantly induces stress and
      anxiety-related behavior in rats (Tab. 2, Fig. 9, Ref. 19).

PMID- 22979906
TI  - The effect of different doses of flumazenil on acetaminophen toxicity in rats.
AB  - BACKGROUND: Acetaminophen is an analgesic drug that is used safely in therapeutic
      doses. At high doses, it causes hepatotoxicity, resulting in hepatic necrosis.
      Some medications and methods are available for treatment of acetaminophen
      overdose. However, results are inconsistent, and sufficient outcomes cannot
      always be obtained. OBJECTIVE: The mechanism of action of acetaminophen has not
      been fully understood. It has been suggested that it exerts its effects on GABA
      receptors. Flumazenil has been experimentally proven to produce an antagonism on
      acetaminophen's analgesic effect.The purpose of this study was to determine
      whether flumazenil antagonized the toxic effects of acetaminophen overdose in
      rats. METHODS: A total of 49 Wistar albino rats weighing between 250 - 350 g were
      used in the study. Nine rats were examined for a preliminary study, and the other
      rats were randomly divided into five groups with eight subjects in each. CONTROL
      GROUP: Saline; Acetaminophen group: 3 g/kg acetaminophen; Experimental Group F1:
      3 g/kg acetaminophen + 0.1 mg/kg flumazenil; Experimental group F2: 3 g/kg
      acetaminophen + 1 mg/kg flumazenil; Experimental group F3: 3 g/kg acetaminophen +
      10 mg/kg flumazenil. Acetaminophen was administered in a 3 ml saline solution by
      way of gastric catheter. Flumazenil was administered by way of intraperitoneal
      injections. Serum levels of acetaminophen, AST, ALT, LDH, ALP and bilirubin were
      recorded over a 24-hour period. RESULTS: Serum acetaminophen levels were similar
      between the groups. The AST, ALT, ALP, LDH, total bilirubin and direct bilirubin
      levels of Group A were significantly higher compared with the Group C, Group F1,
      Group F2 and Group F3. There was not a statistically significant difference in
      the AST, ALT, ALP, LDH, total bilirubin or direct bilirubin levels of the
      flumazenil-administered groups. CONCLUSION: Flumazenil's prevention of the
      acetaminophen-induced increase in liver enzymes is promising. There is some
      indication that flumazenil could be used in treatment of acetaminophen
      intoxication (Tab. 2, Ref. 25).

PMID- 22979907
TI  - Radiological evaluation of the effect of biphasic calcium phosphate scaffold
      (HA+TCP) with 5, 10 and 20 percentage of porosity on healing of segmental bone
      defect in rabbit radius.
AB  - The objective of this study is to radiologically evaluate the effects of biphasic
      calcium phosphate scaffold with 5, 10 and 20 percentage of porosity on cortical
      bone repair in rabbits. In this study, 28 male white rabbits were examined.
      Rabbits were divided into four groups. After induction of general anesthesia, a
      segmental bone defect of 10 mm in length was created in the middle of the right
      radius shaft. In group A, the defect was stabilized with miniplate and 2 screws
      and left untreated. In groups B, C and D tricalcium phosphate scaffold mixed with
      hydroxyapatite (TCP+HA) with 5%, 10% and 20% porosity was used to fi ll the bone
      defect. Bone regeneration and HA+TCP scaffold resorption were assessed by X-ray
      at 1, 2 and 3 months after the surgery. In group A, 3 months after surgery,
      periosteal callus was not found but intercortical callus was observed. In groups
      B and C, 3 months after surgery medullary bridging callus and intercortical
      callus were found, periosteal callus was not found, TCP+HA scaffold were
      observed. In group D, 2 months after the surgery, medullary bridging callus and
      intercortical callus were found, 3 months later, periosteal callus was not found,
      most of scaffold had disappeared and were unclear and partial bone formation was
      recognized. Differences observed in radiological findings were significant
      between group A and groups B, C, D. Differences between groups B and C were not
      significant, but between group D and groups B and C were significant. The results
      of this study showed that TCP+HA scaffold is an osteoconductive and
      osteoinductive biomaterial. Scaffold of TCP+HA can increase the amount of newly
      formed bone and more rapid regeneration of bone defects. These results suggest
      TCP+HA scaffold may considerably be used in the treatment of cortical bone defect
      and other orthopaedic defects PCL (Tab. 2, Fig. 4, Ref. 20).

PMID- 22979908
TI  - Serum osteopontin and CD44 levels in lymphoreticular malignancies in children.
AB  - OBJECTIVE: Osteopontin (OPN) is an adhesive glycoprotein that interacts with a
      variety of cell surface receptors, including several integrins and CD44. OPN is
      expressed and secreted by numerous human malignancies. CD44 play an important
      role in tumor growth and metastasis. We aimed to evaluate serum levels of
      osteopontin and CD44 in patients with lymphorethicular malignancies in childhood.
      METHODS: We studied serum levels of CD44 and OPN levels of 54 patients (26, 18
      and 10 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and
      acute lymphoblastic leukemia (ALL), respectively) at the diagnosis. RESULTS: The
      mean levels of OPN were significantly higher in patients (5.42+/-8.24 ng/ml) than
      in controls (3.89 +/-1.96 ng/ml). The mean levels of CD44 levels were also
      significantly higher in patients (3.82+/-2.31 ng/ml) than in controls (1.96+/
      0.62 ng/ml), and significantly higher in the advanced stages than in early
      stages. The mean levels of the CD44 in NHL, HL and ALL were 3.49+/-2.00, 3.56+/
      1.74, and 5.15+/-3.50 respectively. OPN and CD44 levels were found to be
      increased in parallel (p=0.003). A more advanced disease and/or poor prognostic
      factors were seen in 9 patients who had both serum CD44 and OPN levels higher
      than 2SD of the control. CONCLUSION: Elevated levels of both CD44 and OPN at the
      diagnosis may predict an unfavorable outcome in childhood leukemias and lymphomas
      (Tab. 2, Fig. 3, Ref. 44).

PMID- 22979909
TI  - Morphometry and magnetic resonance imaging of anterior cruciate ligament and
      measurement of secondary signs of anterior cruciate ligament tear.
AB  - Injuries or over-stretching of the anterior cruciate ligament (ACL) may lead to
      its malfunctioning. ACL tear, partial or complete, canto the result of contact or
      non-contact injuries. To conduct morphometry of ACL, twenty six knees (14 right
      and 12 left) were examined in 21 male and 5 female formalin fixed cadavers.
      Measurement of tibial foot print of ACL, distance of its anterior edge from the
      anterior margin of tibia, length and width of ACL were determined with the help
      of digital caliper. Indirect signs of ACL tear (sagittal ACL-tibial angle,
      coronal ACL - tibial angle, Blumensaat line - ACL angle and angle of inclination
      of the intercondylar roof) complement the magnetic resonance imaging (MRI)
      diagnosis of ACL injury. We also studied the consequences of meniscal and
      posterior cruciate ligament injuries on above mentioned angles. In addition 84
      MRI images of knees of patients aged between 18 - 74 years were evaluated for
      diagnosis of any disruption in the morphology of ACL. In our study, mean length
      of the tibial foot print of ACL was 18.34 +/- 3.49 mm, mean width of tibial foot
      print was 15.26 +/- 2.01, mean distance from the anterior edge of tibia to
      anterior margin of attachment of ACL was 13.11 +/- 2.34, length and width of ACL
      were 32.5 +/- 4.33 mm and 9.38 +/- 1.58 mm, respectively. The present study will
      be useful for enhancing the knowledge of anatomy of ACL and may act as a valuable
      guide for radiologists in evaluating the injury to knee involving ACL, menisci
      and PCL (Tab. 5, Fig. 9, Ref. 17). KEYWORDS: anterior cruciate ligament, magnetic
      resonance imaging, posterior cruciate ligament, meniscus, tibia, tear, injury.

PMID- 22979910
TI  - Does ovarian endometrioma affect the number of oocytes retrieved for in vitro
      fertilization?
AB  - OBJECTIVE: To investigate the effects of ovarian endometrioma on the number of
      oocytes retrieved for in vitro fertilization (IVF). BACKGROUND: The presence of
      endometrioma may be the most important predictor of a poor reproductive outcome.
      Literature data suggest that ovarian endometriomas might affect the response to
      ovarian stimulation and oocyte retrieval. METHODS: The present retrospective
      study evaluates 2,023 women who applied to our center with an infertility
      complaint. Twenty-nine women with endometriomas (group 1) who were treated with
      IVF were included in the study. They were compared with 51 women with unexplained
      infertility (group 2) regarding the number of retrieved oocytes after egg
      retrieval and number of metaphase II oocytes. The diagnosis of endometrioma was
      made via ultrasound examination with the identification of low-density cystic
      masses in the ovaries. The patients underwent a controlled ovarian
      hyperstimulation (COH) with either the long agonist mini-dose protocol or the
      multi-dose antagonist protocol. RESULTS: The incidence of endometrioma in
      infertile women was found to be 1.4 %. The women's ages ranged between 24 and 45
      years, and the duration of their infertility ranged between 12 and 216 months.
      The endometrioma was bilateral in 24 % of the cases. The mean endometrioma
      diameter was 26.2+/-7.3 mm for the right ovary and 23.2+/-6.1 mm for the left
      ovary. The average number of retrieved oocytes after egg retrieval in groups 1
      and 2 was 12.4+/-8.3 and 12.2+/-8.6, respectively. The average number of
      metaphase II oocytes in groups 1 and 2 was 8.6+/-6.1 and 9.4+/-7.3, respectively.
      The number of retrieved oocytes after egg retrieval and the number of metaphase
      II oocytes in both endometrioma group and unexplained infertile group were
      similar (p >0.05). CONCLUSION: Endometrioma did not reduce the number of
      retrieved oocytes in a COH cycle for IVF treatment. However it should be noted
      that the ovarian response is affected by the size of endometriomas, bilaterality,
      previous surgeries, recurrence, and the patient's age (Tab. 1, Ref. 31).

PMID- 22979911
TI  - The effect of antiseptic solution in central venous catheter care.
AB  - AIM: Intravenous catheters have become one of the essential tools of modern
      medicine. Preventive measures taken while the catheter is being inserted or in
      place can provide a significant reduction in catheter-related infections and
      bacteremia/sepsis.This study aims to evaluate whether the patient's age and
      gender, the presence of malignancy and coexisting diseases, catheter duration,
      use of total parenteral nutrition solution, blood products, and antibiotics as
      well as antiseptics applied while attaching the central venous catheter
      (chlorhexidine and povidone-iodine) affect the development of catheter
      colonization and catheter-related bloodstream infections in patients with central
      venous catheters. MATERIALS AND METHODS: Our study includes 50 cases which were
      admitted to Izmir Ataturk Training and Research Hospital, I. Surgical Clinic,
      hospitalized due to various reasons between the dates of January-December 2010
      and required catheter use. Patients were randomly assigned to one of the two
      operating rooms, in one of which the insertion site was disinfected with
      Poviiodeks(r) (10 % povidone-iodine) while in the other, (latter) Savlosol(r) (15
      % cetrimide, 1.5 % Chlorhexidine-gluconate, ethanol) was used. RESULTS: Among
      many factors examined in our study, only the use of clorhexidine versus iodine
      povidon in skin antisepsis was found to be statistically significant in the
      reduction of CRBSI and CC (for CRBSI p=0.022 and for CC p=0.047). CONCLUSIONS:
      Our study concludes that skin antisepsis is the only determining factor in the
      prevention of blood infection and colonization due to central venous catheter
      application and the use of clorhexidine vs. povidon is proven to be statistically
      significant (Tab. 1, Ref. 27).

PMID- 22979912
TI  - Do the calcifications in the thyroid gland predict malignancy?
AB  - BACKGROUND: The purpose of this study was to determine the relationship between
      calcifications in the thyroid gland and malignant thyroid lesions. METHODS: From
      June 2005 - May 2010, 169 patients, who had been operated on for thyroidectomy,
      were evaluated. The demographic findings were analyzed with regard to
      ultrasonographic and histopathologic calcifications. The relationship between
      calcifications and malignant and benign thyroid lesions was statistically
      determined by SPSS 10.01 version of Z-test and Chi-square test. RESULTS:
      Microcalcifications were found in 54 patients (31.95 %). Macrocalcification was
      found in one patient (0.59 %).Malignancy was determined in 29 patients (17.16 %).
      The rate of malignancy in patients with calcifications was 17/55 (30.9 1%). The
      diagnosis was nodular colloidal goiter in 38 patients (38/55, 69.09 %) with
      calcifications. The rate of calcification in malignant patients was 17/29 (58.62
      %). The rate of malignancy in patients without calcification was 12/114 (10.52
      %). The difference between the rate of malignancy in patients with calcification
      and the rate of malignancy in patients without calcification was statistically
      significant (Z-test, p < 0.001). CONCLUSION: Microcalcifications of the thyroid
      gland could predict malignant thyroid disease. They should be strictly evaluated
      by all thyroid cancer diagnostic modalities and surgical treatment should also be
      considered (Tab. 4, Ref. 29).

PMID- 22979913
TI  - Comparison of antibacterial effects of oral rinses chlorhexidine and herbal mouth
      wash in patients admitted to intensive care unit.
AB  - BACKGROUND AND PURPOSE: Mouthwashes decrease the risk of VAP by reducing the
      number of microorganisms and their transmission and colonization in the lung.
      Among the oral rinses, chlorhexidine is considered as the gold standard but it
      has a variety of complications. The purpose of this study was to determine and
      compare anti-bacterial effects of the chlorhexidine gluconate and herbal
      mouthwashes in intensive care unit patients. MATERIALS AND METHODS: In this
      double blind randomized clinical trial, 60 patients who were admitted in ICU were
      divided into two equal 30 persons groups. In the first group Chlorhexidine
      gluconate 2 % mouthwash and in the second group herbal mouth wash was used. Just
      before and again after 6 min of oral rinsing, salivary samples were obtained
      without any stimulation in order to culture Staphylococcus aureus and
      Streptococcus pneumoniae. The data were processed in SPSS16 software and were
      analyzed by appropriate statistical tests. RESULTS: Matrica(r) and chlorhexidine
      mouthwashes have significant antibacterial effects against Streptococcus
      pneumoniae and Staphylococcus aureus. Decreasing of the number of bacteria in
      samples after oral rinsing was significant in both groups (p <0.001) but
      chlorhexidine was significantly more effective than herbal mouth wash in reducing
      the number of colonies (p < 0.001). CONCLUSION: The herbal mouth wash has
      significant antibacterial effects against Staphylococcus aureus and Streptococcus
      pneumoniae, but its efficacy is less than chlorhexidine, so after further
      investigation, it would be considered as an alternative to chlorhexidine in ICUs
      (Tab. 3, Ref. 33).

PMID- 22979914
TI  - Cu/Zn-superoxide dismutase, paraoxonase and arylesterase activities and
      malondialdehyde levels in patients with familial mediterranean fever.
AB  - OBJECTIVES: In this study, alterations in antioxidant enzyme activities and
      malondialdehyde (MDA) levels in the serum samples of patients with familial
      Mediterranean fever (FMF), an autosomal recessive disease characterized by
      recurrent episodes of peritonitis, pleuritis, arthritis and fever, were
      investigated and compared with those of age- and sex-matched healthy controls.
      METHODS: Twenty-five patients with FMF undergoing colchicine therapy at doses of
      1-1.5 mg and 25 age- and sex-matched healthy controls were included in the study.
      In the patients with FMF and control subjects, the erythrocyte sedimentation rate
      (ESR) and C-reactive protein (CRP) level were measured. Cu/Zn-superoxide
      dismutase (Cu/Zn-SOD), paraoxonase-1 (PON-1) and arylesterase (ARE) enzyme
      activities and MDA levels as a production of lipid peroxidation were evaluated
      using the appropriate methods. RESULTS: No statistically significant differences
      in the serum levels of ESR, CRP, Cu/Zn-SOD, MDA and PON-1 between the groups were
      observed (p>0.05). Serum ARE activity was significantly decreased in the patients
      with FMF compared with the control subjects (p<0.01). CONCLUSION: In conclusion,
      some abnormalities in the antioxidant defense system and lipid peroxidation may
      be observed in FMF patients during attack-free periods. However, further long
      term studies on the subject are needed to explore altered lipid peroxidation and
      antioxidant defense mechanisms in patients with FMF (Tab. 1, Fig. 1, Ref. 35).

PMID- 22979915
TI  - The effect of obstructive sleep apnea-hypopnea syndrome on acute myocardial
      infarction.
AB  - BACKGROUND AND OBJECTIVES: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is
      the most clinically common type of sleep-related breathing disorders. In this
      study, the effect of OSAHS on ST segment elevation myocardial infarction (STEMI)
      was investigated. METHODS: Seventy-five patients with STEMI were included in this
      study. The patients were divided into two groups: STEMI accompanied by OSAHS (O+)
      group (33 patients) and STEMI without OSAHS (O-) group (42 patients). The
      differences of the clinical characteristics between the two groups were compared.
      The relationship between oxyhemoglobin desaturation index (ODI) and Gensini
      Score, and the relationships between OSAHS and clinical parameters were analyzed
      by a regression analysis. RESULTS: AMI mainly occurred from 10 pm to 6 am in the
      O+ group (45.5 %) and from 6 am to 2 pm in the O-group (52.3 %). The peak of
      serous creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), N
      terminal Pro-brain natriuretic peptide (NT-proBNP), and left ventricle end
      diastolic volume index (LVEDVI) were significantly increased in the O+ group
      compared to the O- group, while the left ventricular ejection fraction (LVEF)
      were significantly decreased. The regression analysis showed that ODI was
      positively correlated with Gensini Score, while serous CK, hs-CRP, NT-proBNP, and
      OSAHS were independently associated with left ventricular insufficiency (LVI),
      and the incidence of LVI in O+ group was 5.8 times as O- group. CONCLUSIONS: In
      STEMI patients with OSAHS, myocardial infarction mainly occurred from 10 pm to 6
      am, and the incidence of LVI was significantly higher than STEMI patients without
      OSAHS (Tab. 5, Fig. 2, Ref. 26).

PMID- 22979916
TI  - Fusion of the 2nd maxillary molar with the impacted 3rd molar.
AB  - Subject matter: The dentist has to deal with complicated cases of fused molars,
      which are rather rare and morphologically very varied. A wrong or incomplete
      diagnosis can considerably complicate a planned therapy. CASE REPORT: The authors
      describe a case of apical periodontal complication of fused teeth that had to be
      removed surgically. The upper 2nd molar fused with the impacted 3rd molar and was
      diagnosed for extraction. CONCLUSION: Even a careful diagnostic procedure and X
      ray image sometimes may not indicate the exact location and mutual position of
      the fused teeth. The authors make us aware of the possible occurrence of fused
      roots, and the necessity to inform the patient ahead of time about the course of
      endodontic or surgical interventions, possible complications and their removal.
      They describe the positive influence of PRP (platelet rich plasma) in wound
      healing. In order to establish the exact indication and therapy, they emphasize
      the importance of using CT imaging diagnostics or a 3D-CT examination (Fig. 7,
      Ref. 15).

PMID- 22979917
TI  - Integrating paleobiology, archeology, and history to inform biological
      conservation.
AB  - The search for novel approaches to establishing ecological baselines (reference
      conditions) is constrained by the fact that most ecological studies span the past
      few decades, at most, and investigate ecosystems that have been substantially
      altered by human activities for decades, centuries, or more. Paleobiology,
      archeology, and history provide historical ecological context for biological
      conservation, remediation, and restoration. We argue that linking historical
      ecology explicitly with conservation can help unify related disciplines of
      conservation paleobiology, conservation archeobiology, and environmental history.
      Differences in the spatial and temporal resolution and extent (scale) of
      prehistoric, historic, and modern ecological data remain obstacles to integrating
      historical ecology and conservation biology, but the prolonged temporal extents
      of historical ecological data can help establish more complete baselines for
      restoration, document a historical range of ecological variability, and assist in
      determining desired future conditions. We used the eastern oyster (Crassostrea
      virginica) fishery of the Chesapeake Bay (U.S.A.) to demonstrate the utility of
      historical ecological data for elucidating oyster conservation and the need for
      an approach to conservation that transcends disciplinary boundaries. Historical
      ecological studies from the Chesapeake have documented dramatic declines (as much
      as 99%) in oyster abundance since the early to mid-1800 s, changes in oyster size
      in response to different nutrient levels from the sixteenth to nineteenth
      centuries, and substantial reductions in oyster accretion rates (from 10 mm/year
      to effectively 0 mm/year) from the Late Holocene to modern times. Better
      integration of different historical ecological data sets and increased
      collaboration between paleobiologists, geologists, archeologists, environmental
      historians, and ecologists to create standardized research designs and
      methodologies will help unify prehistoric, historic, and modern time perspectives
      on biological conservation.

PMID- 22979918
TI  - Response to 'Fragment of tegument protein pp65 of human cytomegalovirus induces
      autoantibodies in BALB/c mice'.

PMID- 22979919
TI  - Atmospheric-pressure plasma-enhanced chemical vapor deposition of a-SiCN:H films:
      role of precursors on the film growth and properties.
AB  - Atmospheric pressure plasma enhanced chemical vapor deposition (AP-PECVD) using
      Surfx Atomflow(TM) 250D APPJ was utilized to synthesize amorphous silicon
      carbonitride coatings using tetramethyldisilizane (TMDZ) and hexamethyldisilizane
      (HMDZ) as the single source precursors. The effect of precursor chemistry and
      substrate temperature (T(s)) on the properties of a-SiCN:H films were evaluated,
      while nitrogen was used as the reactive gas. Surface morphology of the films was
      evaluated using atomic force microscopy (AFM); chemical properties were
      determined using Fourier transform infrared spectroscopy (FTIR); thickness and
      optical properties were determined using spectroscopic ellipsometry and
      mechanical properties were determined using nanoindentation. In general, films
      deposited at substrate temperature (T(s)) < 200  degrees C contained organic
      moieties, while the films deposited at T(s) > 200  degrees C depicted strong Si-N
      and Si-CN absorption. Refractive indices (n) of the thin films showed values
      between 1.5 and 2.0, depending on the deposition parameters. Mechanical
      properties of the films determined using nanoindentation revealed that these
      films have hardness between 0.5 GPa and 15 GPa, depending on the T(s) value. AFM
      evaluation of the films showed high roughness (R(a)) values of 2-3 nm for the
      films grown at low T(s) (<250  degrees C) while the films grown at T(s) >= 300 
      degrees C exhibited atomically smooth surface with R(a) of ~0.5 nm. Based on the
      gas-phase (plasma) chemistry, precursor chemistry and the other experimental
      observations, a possible growth model that prevails in the AP-PECVD of a-SiCN:H
      thin films is proposed.

PMID- 22979920
TI  - Significant improvement of sperm DNA quality after microsurgical repair of
      varicocele.
AB  - Varicocele is currently the most common irregularity identified in males that is
      associated with impaired spermatogenesis. It primarily presents in the form of
      decreased sperm count and motility, abnormal morphology, and significantly
      increased sperm DNA fragmentation. Several studies have shown that surgical
      repair improves semen parameters and increases the odds of spontaneous pregnancy.
      However the exact effect of surgical repair treatment remains controversial.
      Therefore, the aim of our study was to evaluate the effectiveness of
      microsurgical repair by comparing common semen parameters and sperm DNA
      fragmentation index (DFI). We evaluated infertile men (n = 19) who underwent
      microsurgical subinguinal varicocelectomy for treatment of clinical varicocele
      before and 3 months after surgery. Normozoospermic men (n = 19) were considered
      as the normal control group. Semen parameters improved significantly after
      surgery when compared with that before surgery, but still significant differences
      with the normal control group were observed. In comparison, sperm DNA integrity
      improved significantly after surgery (percentage DFI decreased from 28.4 +/-
      15.6% before surgery to 22.4 +/- 12.9%, at 3 months post surgery) to similar
      levels as the normal control group. These results suggest that microsurgical
      repair may be considered as a treatment option in infertile men with palpable
      varicocele.

PMID- 22979921
TI  - Evaluation of the pharmacological activity of the Alternanthera brasiliana
      aqueous extract.
AB  - CONTEXT: Alternanthera brasiliana (L.) Kuntze (Amarantaceae) is widely used in
      Brazilian traditional medicine as an analgesic, anti-inflammatory and
      antibacterial. OBJECTIVE: To investigate the potential anti-inflammatory,
      analgesic, anxiolytic, and locomotor effect of the infusions in preclinical
      models. MATERIALS AND METHODS: Anti-inflammatory activity was evaluated by a
      carrageenan-induced pleurisy test in Wistar rats (200 and 400 mg/kg, n = 6-7).
      Analgesic activity was evaluated by the number of abdominal contractions induced
      by 0.6% acetic acid administered to Swiss mice (25, 50, 100, 200, and 400 mg/kg,
      n = 10). Effects on the central nervous system (CNS) were evaluated in Wistar
      rats (100, 200, and 400 mg/kg, n = 10) using open field and plus maze models.
      RESULTS AND DISCUSSION: Possible anti-inflammatory activity was indicated by the
      significant reduction of 19.8% for 200 mg/kg (p < 0.05) and 23.9% for 400 mg/kg
      (p < 0.05) of polymorphonuclear cells in pleural exudate. Analgesic activity was
      suggested by the significant reduction (p < 0.01) of number of abdominal
      contractions for all doses under study. No anxiolytic effect was noted, but there
      was an increase in the number of rearings in the group of rats treated with 100
      mg/kg dose (p < 0.05). CONCLUSIONS: Our findings suggest that the aqueous extract
      of the leaves of A. brasiliana has a potential pharmacological effect on
      inflammation and pain.

PMID- 22979922
TI  - Recruitment maneuver after apnea test or continuous positive airway pressure
      apnea test?

PMID- 22979923
TI  - Genetic diversity and demographical history of Coilia ectenes (Clupeiformes:
      Engraulidae) inferred from the complete control region sequences of mitochondrial
      DNA.
AB  - Coilia ectenes is a commercially important fishery species. In this study,
      genetic diversity and population structure of C. ectenes were examined by using
      mitochondrial DNA control region sequences in 246 individuals sampled from 10
      localities in China. One hundred and ninety-five polymorphic sites defined 184
      distinct haplotypes, revealing a moderately high haplotype diversity (Hd) and a
      relatively low nucleotide diversity (pi) in the 10 localities. An excess of
      unique haplotypes at most sample locations were detected, which might influence
      the genetic structure of the C. ectenes populations. Hd ranged from 0.939 to
      1.000 and pi ranged from 0.26% to 1.15%. The Dongting fish population had the
      highest pi level. The genetic distances ranged from 0.26% to 1.03% within
      populations and from 0.56% to 4.90% between populations. The distances between
      the Fuzhou (FZ) population and other populations were mostly >4.8%. Neighbor
      joining tree indicated distinct patterns of phylogeographic structure among
      haplotypes from FZ population and those from other populations. Analyses of
      molecular variance and F(st) statistics suggested that the divergence existed
      among populations from 10 localities, indicating that gene flow might be
      restricted among those regions, despite the wide dispersal. In addition, neutral
      tests and analysis of mismatch distribution suggested that C. ectenes might have
      undergone a population expansion. Our study revealed the extant population
      genetic diversity and structure of the C. ectenes, and was in favor of the
      related fishery management issues including fishery stock identification and
      conservation.

PMID- 22979924
TI  - [The development and current status of integrative medicine at UCLA].

PMID- 22979925
TI  - [Target points: a discussion on acupuncture treatment of primary trigeminal
      neuralgia].
AB  - In this paper, issues of acupuncture using target points and depth of needling
      were discussed based on the theory of traditional Chinese medicine acupoints and
      combined with anatomical and neurological research of Western medicine. The
      theoretical evidence of acupuncture on nerve foramen and ganglion and the reasons
      for being nonstandard operating on acupoints were analyzed. This study summarized
      the method of using acupuncture at Xiaguan (ST7), Cuanzhu (BL2), Sibai (ST2) and
      Jiachengjiang acupoints to align with the spheno-palatine ganglion and additional
      nerve foramen (supraorbital, infraorbital and mental foramina) to treat primary
      trigeminal neuralgia. This study adhered to the Standards for Reporting
      Interventions in Clinical Trials of Acupuncture and helped in development of
      study standardization for acupuncture processes. The authors hoped that should
      help in significantly diminishing risk and improving therapeutic efficacy in
      clinic.

PMID- 22979926
TI  - Two-factor designs unable to examine the interactions (Part 2).
AB  - Two-factor designs are very commonly used in scientific research. If the two
      factors have interactions, research designs like the factorial design and the
      orthogonal design can be adopted; however, these designs usually require many
      experiments. If the two factors have no interaction or the interaction is not
      statistically significant on result in theory and in specialty, and the measuring
      error of experimental data under a certain condition (usually one of the
      experimental conditions that are formed by the complete combination of the levels
      of the two factors) is allowed in specialty, researchers can use random block
      design without repeated experiments, balanced incomplete random block design
      without repeated experiments, single factor design with a repeatedly measured
      factor, two-factor design without repeated experiments and two-factor nested
      design. This article introduces the last two design types by examples.

PMID- 22979927
TI  - [Investigation on response of the patient-reported outcome scale of the main
      symptoms of chronic obstructive pulmonary disease complicated with pulmonary
      heart disease].
AB  - OBJECTIVE: To select appropriate descriptors for response of the patient-reported
      outcome (PRO) scale for the main symptoms of patients with chronic obstructive
      pulmonary disease (COPD) complicated with pulmonary heart disease. METHODS: A
      cross-sectional investigation was carried out. Five equidistant ordinal
      descriptive words in the PRO scale of main symptoms for COPD complicated with
      pulmonary heart disease were selected. There were 32 alternative words in the
      questionnaire. Thirty respondents were required to place each descriptive word on
      a 10-centimeter line according to where they considered each descriptive word
      should be placed. Then, the line was measured by ruler; average, standard
      deviation and median were calculated by excel software; the authors finally chose
      the five equidistant words which accurately reflect the degree of main symptoms.
      RESULTS: The five most appropriate descriptive words were selected; they were
      "never", "seldom", "half-partly sometimes", "very often" and "always".
      CONCLUSION: These selected decorated words are suitable for the PRO scale for
      patients with COPD complicated with pulmonary heart disease.

PMID- 22979928
TI  - [Analysis of syndrome discipline of generalized anxiety disorder using data
      mining techniques].
AB  - OBJECTIVE: To study the use of data mining techniques in analyzing the syndrome
      discipline of generalized anxiety disorder (GAD). METHODS: From August 1, 2009 to
      July 31, 2010, 705 patients with GAD in 10 hospitals of Beijing were investigated
      over one year. Data mining techniques, such as Bayes net and cluster analysis,
      were used to analyze the syndrome discipline of GAD. RESULTS: A total of 61
      symptoms of GAD were screened out. By using Bayes net, nine syndromes of GAD were
      abstracted based on the symptoms. Eight syndromes were abstracted by cluster
      analysis. After screening for duplicate syndromes and combining the experts'
      experience and traditional Chinese medicine theory, six syndromes of GAD were
      defined. These included depressed liver qi transforming into fire, phlegm-heat
      harassing the heart, liver depression and spleen deficiency, heart-kidney non
      interaction, dual deficiency of the heart and spleen, and kidney deficiency and
      liver yang hyperactivity. Based on the results, the draft of Syndrome Diagnostic
      Criteria for Generalized Anxiety Disorder was developed. CONCLUSION: Data mining
      techniques such as Bayes net and cluster analysis have certain future potential
      for establishing syndrome models and analyzing syndrome discipline, thus they are
      suitable for the research of syndrome differentiation.

PMID- 22979929
TI  - [Study on the correlation between traditional Chinese medicine syndrome and short
      term prognosis of ischemic stroke using logistic regression model and repeated
      measures analysis of variance].
AB  - OBJECTIVE: To investigate the correlation between traditional Chinese medicine
      (TCM) syndrome and short-term prognosis of ischemic stroke. METHODS: TCM syndrome
      factors and the neurological deficit degree of 464 patients with ischemic stroke
      were assessed using the Ischemic Stroke TCM Syndrome Factor Diagnostic Scale
      (ISTSFDS) and National Institutes of Health Stroke Scale (NIHSS) on the 1st, 7th
      and 14th day from the onset of ischemic stroke. Patients were assigned to the
      favorable short-term prognosis group and the unfavorable short-term prognosis
      group, depending on the NIHSS score on the 14th day after onset of stroke. The
      correlation between TCM syndrome factors and the short-term prognosis of ischemic
      stroke was studied using the logistic regression model. Then, the receiver
      operating characteristic (ROC) curves were used to evaluate the predicting
      capacity of logistic regression mode. Lastly, according to the results of the
      logistic regression model, the authors investigated the correlation between blood
      stasis syndrome and the neurological deficit degree of stroke with application of
      repeated-measures analysis of variance. RESULTS: Blood stasis syndrome (odds
      ratio=2.924, 95% confidence interval from 1.231 to 6.946, P=0.015) on the 14th
      day and NISSS score (odds ratio=1.956, 95% confidence interval from 1.701 to
      2.250, P=0.000) on the 1st day after onset of stroke were risk factors that could
      predict short-term prognosis of ischemic stroke. The area under the ROC curves of
      the logistic regression model was 0.95. There was a tendency for stroke patients
      with blood stasis syndrome to have higher NIHSS scores than patients without
      blood stasis syndrome, and there was a decreased NIHSS score with time points
      delay. CONCLUSION: Blood stasis syndrome is a risk whose diagnosis could predict
      short-term prognosis of ischemic stroke. Clinically, the application of treatment
      focusing on activating blood and resolving stasis can improve the short-term
      prognosis of stroke patients. This study provides an evidence base for dynamic
      intervention of a comprehensive integrative medical treatment program based on
      syndrome differentiation for ischemic stroke.

PMID- 22979930
TI  - [Using nested case-control study to appraise the effectiveness of Chinese
      medicines in the treatment of diabetic nephropathy].
AB  - OBJECTIVE: A nested case-control study was carried out to assess the
      effectiveness of Chinese medicines in the treatment of diabetic nephropathy, so
      as to explore the feasibility of using nested case-control study on effect
      assessment of Chinese medicine. METHODS: Nested case-control study was applied
      and the participants were enrolled from the subjects recruited in a cohort study.
      The cases and the controls were matched by 1 to 4 in age, gender, nationality and
      the stage of diabetic nephropathy when recruited in the cohort study. The EpiData
      3.1 software was used for inputting data and SAS system was used for data
      analysis. Conditional logistic regress was applied to analyze the relationship
      between treatment and the progression of diabetic nephropathy. The study power
      was estimated and the sample sizes for case-control study and cohort study were
      recalculated based on the data from the cohort study. RESULTS: Eight cases and 32
      controls were recruited in this study. The education level, ratio of drug
      withdrawal, change of therapy, syndrome differentiation and treatment were not
      significantly different in case and control groups. The progression of diabetic
      nephropathy was not significantly related with the treatment and the odds ratio
      (OR) value was 0.725 with a 95% confidence interval from 0.174 to 3.030. The
      statistical power of the study was 5%. To achieve the statistical power of 80%, 1
      350 (270:1 080) participants were needed for 1:4 matched case-control study, 880
      (440:440) for 1:1 paired case-control study, and 1 020 (510:510) for 1:1 control
      study. CONCLUSION: The treatment method is not significantly related with the
      progress of diabetic nephropathy. The nested case-control study is applicable in
      the therapeutic effect evaluation of Chinese medicine. Basic studies such as
      cross-sectional studies should be carried out to supply fundamental information
      for other types of studies including case-control study, cohort study and
      randomized clinical trials. Large sample size studies were needed to appraise the
      effect of Chinese medicine.

PMID- 22979931
TI  - [Correlation between facial nerve functional evaluation and efficacy evaluation
      of acupuncture treatment for Bell's palsy].
AB  - OBJECTIVE: To assess and grade facial nerve dysfunction according to the extent
      of facial paralysis in the clinical course of acupuncture treatment for Bell's
      palsy, and to observe the interrelationship between the grade, the efficacy and
      the period of treatment, as well as the effect on prognosis. METHODS: The authors
      employed the House-Brackmann scale, a commonly used evaluation scale for facial
      paralysis motor function, and set standards for eye fissure and lips. According
      to the improved scale, the authors assessed and graded the degree of facial
      paralysis in terms of facial nerve dysfunction both before and after treatment.
      The grade was divided into five levels: mild, moderate, moderately severe, severe
      dysfunction and complete paralysis. The authors gave acupuncture treatment
      according to the state of the disease without artificially setting the treatment
      period. The observation was focused on the efficacy and the efficacy was
      evaluated throughout the entire treatment process. RESULTS: Fifty-three cases out
      of 68 patients with Bell's palsy were cured and the overall rate of efficacy was
      97%. Statistically significant differences (P<0.01) were perceived among the
      efficacy of five levels of facial nerve dysfunction. Efficacy was correlated with
      the damage level of the disease (correlation coefficient r=0.423, P<0.01). The
      course of treatment also extended with the severity of facial nerve dysfunction
      (P<0.01). CONCLUSION: Differences exist in patients with Bell's palsy in terms of
      severity of facial nerve dysfunction. Efficacy is reduced in correlation with an
      increase in facial nerve dysfunction, and the period of treatment varies in need
      of different levels of facial nerve dysfunction. It is highly necessary to assess
      and grade patients before observation and treatment in clinical study, and choose
      corresponding treatment according to severity of damage of the disease.

PMID- 22979932
TI  - [Effects of acupuncture on lactoferrin content in tears and tear secretion in
      patients suffering from dry eyes: a randomized controlled trial].
AB  - BACKGROUND: With the understanding of the immune inflammatory response in the
      pathogenesis of dry eyes, and the limitations of widely used artificial tears and
      numerous pharmaceuticals and methods to promote tear secretion, clinicians pay
      more attention to the therapies that can promote tear secretion actively.
      Acupuncture treatment for dry eye may meet this requirement. OBJECTIVE: To
      observe the clinical efficacy of acupuncture treatment on dry eye and the effects
      on duration, and to examine the mechanisms of acupuncture in treating patients
      with dye eyes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The study was
      performed at Department of Ophthalmology, Shuguang Hospital, Shanghai University
      of Traditional Chinese Medicine from August 2010 to May 2011. Patients with the
      primary diagnosis of dry eye were enrolled. Sixty-five patients were randomly
      divided into treatment group and control group, and were given 3 weeks of
      acupuncture treatment or artificial tear therapy respectively. MAIN OUTCOME
      MEASURES: The enzyme-linked immunosorbent assay was used to detect the
      lactoferrin content of the tears before and after treatment. In order to evaluate
      the efficacy of the treatment methods, the Schirmer I test and break-up time were
      also measured. RESULTS: Compared with before treatment, the lactoferrin content
      in the tears of patients in the treatment group increased, break-up time was
      prolonged and the result of the Schirmer I test showed improvement after 3 weeks
      of treatment. The indexes mentioned above did not change in the control group
      after treatment. There were no significant differences in tear lactoferrin and
      Schirmer I test between one week after treatment and after 3-week treatment in
      the treatment group, but break-up time was significantly shortened. The result of
      Schirmer I test in the treatment group was significantly higher than that in the
      control group one week after treatment. CONCLUSION: Acupuncture can increase tear
      lactoferrin level, extend tear film break-up time and promote tear secretion in
      patients with dry eye in a time-limited trial. With the end of treatment, the
      effect decreased.

PMID- 22979933
TI  - [Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously
      hypertensive rats and the underlying mechanisms].
AB  - OBJECTIVE: To explore the effects of extracts of Radix Scrophulariae (ERS) on
      blood pressure, vasoconstrictors and morphology of artery in spontaneously
      hypertensive rats (SHRs). METHODS: Fifty SHRs were randomly divided into SHR, SHR
      plus 40 mg/kg of captopril, SHR plus 70 mg/kg of ERS, SHR plus 140 mg/kg of ERS
      and SHR plus 280 mg/kg of ERS groups. Wistar-Kyoto (WKY) rats were randomly
      divided into two groups, namely, WKY and WKY plus 140 mg/kg of ERS groups. The
      rats were orally administered with the corresponding drugs or drinking water once
      a day for 20 weeks. The blood pressure was determined every three weeks. At the
      21st week, the concentrations of noradrenaline (NA), angiotensin II (Ang II),
      thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1alpha) in serum and
      endothelin-1 (ET-1) were detected by enzyme-linked immunosorbent assay. The
      morphological changes in abdominal aorta were observed under an optical
      microscope with hematoxylin and eosin staining. The ratio of intima-media
      thickness/lumen radius of abdominal aorta was calculated. RESULTS: ERS
      significantly lowered the blood pressure of SHRs from the 3rd to the 21st week;
      ERS also reduced the levels of NA, Ang II, ET-1 and TXB(2), decreased the intima
      media thickness of abdominal aortal wall and improved the morphological changes
      in abdominal aorta in SHRs. In addition, ERS did not significantly change blood
      pressure and vasoactive substances in WKY rats. CONCLUSION: ERS possesses
      beneficial effects in inhibiting hypertension and attenuating arteriosclerosis.
      The underlying mechanism may be associated with restraining the release of
      vasoconstrictors, such as NA, Ang II, ET-1 and TXB(2).

PMID- 22979934
TI  - [Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled
      receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in
      rats with Parkinson disease].
AB  - OBJECTIVE: To investigate the effects of Tianqi Pingchan (TQPC) Granule, a
      compound traditional Chinese herbal medicine with antitremor activity, on
      levodopa-induced dyskinesia and the expression of G protein-coupled receptor
      kinase 6 (GRK6) in rats with Parkinson disease (PD). METHODS: The hemi
      Parkinsonian rat model was established by sterotaxically injecting 6-hydroxydopa
      (6-OHDA) to the right medial forebrain bundle. Rats with PD were randomly divided
      into 5 groups with 5 in each. PD group was intraperitoneally injected with
      vitamin C; levodopa group was intraperitoneally injected with levodopa and
      benserazide; low-, medium- and high-dose TQPC Granule groups were
      intraperitoneally injected with levodopa and benserazide and treated with
      different dosages of TQPC Granule by gavage for 29 d. Another 5 rats were served
      as control with sham-operation. The behaviors of rats were observed and
      classified with abnormal involuntary movement (AIM) score. The expression of GRK6
      in the striate of rats was detected by immunohistochemical method and Western
      blotting. RESULTS: AIM score was increased and the expression of GRK6 protein in
      lesion side was decreased after the long-tern treatment with levodopa and
      benserazide in rats. The AIM scores of rats with PD were decreased after TGPC
      Granule treatment. Immunohistochemical results showed that the number of GRK6
      positive cells in medium- and high-dose TQPC Granule groups was increased as
      compared to that in the levodopa group (P<0.05). The expression level of GRK6
      protein was increased in medium-dose TQPC Granule group when compared with the
      levodopa group (P<0.01), which was observed by Western blotting. CONCLUSION: TGPC
      Granule can increase the expression of GRK6, inhibit the increase of AIM, and
      reduce the incidence of levodopa-induced dyskinesia in rats with PD.

PMID- 22979935
TI  - Chelidonine isolated from ethanolic extract of Chelidonium majus promotes
      apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways.
AB  - OBJECTIVE: To evaluate the role of chelidonine isolated from ethanolic extract of
      Chelidonium majus in inducing apoptosis in HeLa cells and to assess the main
      signalling pathways involved. METHODS: Cells were initially treated with
      different concentrations of chelidonine for 48 h and the median lethal dose
      (LD50) value was selected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay. Morphological analysis of nuclear condensation and DNA damage and
      fragmentation were measured by 4',6-diamidino-2-phenylindole staining and comet
      assay. Further, reactive oxygen species (ROS) generation, cell cycle arrest and
      change in mitochondrial membrane potential were also examined and analyzed by
      flow cytometry. Evaluation of interaction of drug with CT DNA was investigated by
      circular dichroism (CD) spectral analysis to find any possible drug-CT DNA
      interaction. The mRNA and protein expressions of major signal proteins like p38,
      p53, protein kinase B (AKT), phosphatidylinositol 3-kinases (PI3K), Janus kinase
      3 (JAK3), signal transducer and activator of transcription 3 (STAT3) and E6 and
      E7 oncoproteins as well as the pro-apoptotic genes and antiapoptotic genes were
      also estimated by reverse transcriptase-polymerase chain reaction and Western
      blotting. RESULTS: Based on LD(50) value (30 MUg/mL) of chelidonine, three doses
      were selected, namely, 22.5 MUg/mL (D1), 30.0 MUg/mL (D2) and 37.5 MUg/mL (D3).
      Results showed that chelidonine inhibited proliferation and induced apoptosis in
      HeLa cells through generation of ROS, cell cycle arrest at sub-G1 and G0/G1
      stage, change in mitochondrial membrane potential and fragmentation of DNA.
      Results of CD spectra showed effective interaction between chelidonine and calf
      thymus DNA. Studies of signalling pathway revealed that chelidonine could
      efficiently induce apoptosis through up-regulation of expressions of p38, p53 and
      other pro-apoptotic genes and down-regulation of expressions of AKT, PI3K, JAK3,
      STAT3, E6, E7 and other antiapoptotic genes. CONCLUSION: Chelidonine isolated
      from Chelidonium majus efficiently induced apoptosis in HeLa cells through
      possible alteration of p38-p53 and AKT/PI3 kinase signalling pathways.

PMID- 22979936
TI  - Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation
      responses in rats with stable chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the influence and long-term effects on systemic and local
      inflammation responses in rat with stable chronic obstructive pulmonary disease
      (COPD) treated with traditional Chinese medicine (TCM) for regulating and
      invigorating the lung and kidney, including invigorating the lung and spleen
      (Bufei Jianpi) therapy, supplementing the lung and kidney (Bufei Yishen) therapy,
      and nourishing qi and kidney (Yiqi Zishen) therapy. METHODS: Rats were randomly
      divided into six groups: control, model, aminophyline, Bufei Jianpi, Bufei Yishen
      and Yiqi Zishen groups. The stable COPD model of rat was duplicated by cigarette
      smoke inhalations and bacterial infection. From the ninth week, the rats with
      stable COPD were treated with Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or
      aminophyline respectively until the 20th week. Half of the animals were
      sacrificed at the 20th or 32nd week respectively. The leukocyte count and
      neutrophil percentage in peripheral blood and bronchoalveolar lavage fluid (BALF)
      were measured; levels of interleukin (IL)-8, IL-10 and tumor necrosis factor
      alpha (TNF-alpha) in BALF, and levels of IL-1beta, IL-6, IL-8, IL-10 and TNF
      alpha and soluble tumor necrosis factor receptor II (sTNFR2) in serum and lungs
      were detected by enzyme-linked immunosorbent assay or immunohistochemical method.
      RESULTS: There were no statistical differences in leukocyte count and neutrophil
      percentage in peripheral blood among six groups (P>0.05). At the 20th week,
      leukocyte count in BALF was higher in the model group than in the control group
      (P<0.01), and was lower in the three TCM groups and the aminophyline group than
      in the model group (P<0.05, P<0.01), and that of the Bufei Jianpi group was lower
      than the aminophyline group (P<0.01); while at the 32nd week, leukocyte count in
      BALF of the three TCM groups decreased and was lower than that of the
      aminophyline group (P<0.05, P<0.01). At the 20th and 32nd weeks, levels of IL
      1beta, IL-6, IL-8, IL-10, TNF-alpha and sTNFR2 in serum and lungs, and IL-8, IL
      10 and TNF-alpha in BALF of the model group increased, which were higher than
      those in the control group (P<0.05, P<0.01); the mentioned cytokines were
      decreased in the three TCM groups compared with the model group (P<0.05, P<0.01),
      and were also lower in serum and BALF of the three TCM groups than those of the
      aminophyline group (P<0.05, P<0.01). Expressions of cytokines in lung tissues
      were depressed in the three TCM groups as compared to those in the aminophyline
      group. There was no statistical difference on expressions of the mentioned
      cytokines either in serum and BALF or in the lungs between week 32 and week 20.
      CONCLUSION: The Bufei Jianpi, Bufei Yishen and Yiqi Zishen therapies can
      significantly reduce the systemic and local inflammation responses in rats with
      stable COPD, and have evident long-term effects.

PMID- 22979937
TI  - Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and
      Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.
AB  - OBJECTIVE: To investigate the effects of oral administration of aqueous extract
      of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase
      activities in rats. METHODS: The 25 and 50 mg/(kg.d) of aqueous extracts of H.
      sabdariffa were respectively given to rats in the experimental groups for 28 d,
      and rats in the control group received an appropriate volume of distilled water
      as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney
      were assayed by spectrophotometric method. RESULTS: Administrations of 25 and 50
      mg/(kg.d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)
      Mg(2+)-ATPase activity in the kidney of rats (P<0.05). However, the renal Na(+)
      K(+)-ATPase activity of the experimental rats was not affected by either dose of
      the extract. And the plasma Na(+), K(+) and Ca(2+) levels of the experimental
      rats had no significant changes. Administration of either dose of the extract did
      not result in any significant changes in body and kidney weights, the
      concentrations of plasma albumin and total protein, and alkaline phosphatase,
      aspartate aminotransferase and alanine aminotransferase activities. However,
      concentrations of creatinine and urea were significantly reduced by 50 mg/kg of
      the extract (P<0.05). CONCLUSION: The present study indicates that oral
      administration of aqueous extract of H. sabdariffa may preserve the renal
      function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.

PMID- 22979938
TI  - Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg.
AB  - OBJECTIVE: To study the anticonvulsant activity of alcoholic extract of bark of
      Pinus roxburghii Sarg. (AEPR) used in Indian traditional medicine system in
      treating convulsion. METHODS: Anticonvulsant activity was evaluated by maximal
      electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in Wistar albino
      rats. In the MES model, 150 mA current for 0.2 s was given through ear electrodes
      to induce convulsions in rats. The duration of tonic extension of hind limb was
      used as the end point, namely, prevention or decrease in the duration of hind
      limb extension was considered as a protective action. In the PTZ model, the
      anticonvulsant property of AEPR was assessed by its ability to delay the onset of
      myoclonic spasm and clonic convulsions produced by intraperitoneal administration
      of PTZ. RESULTS: In the MES-induced seizure model, AEPR in doses of 300 and 500
      mg/kg body weight reduced all the phases of convulsion significantly (P<0.01).
      Standard drug phenytoin at a dose of 25 mg/kg significantly reduced flexion phase
      (P<0.01) and abolished all phases of convulsion. In the PTZ-induced seizure
      model, the administration of the extract at doses of 300 and 500 mg/kg 30 min
      prior to injection of PTZ significantly delayed the onset of clonic seizure
      (P<0.01). AEPR at the dose of 100 mg/kg body weight could not exert any
      significant protective effect on PTZ-induced convulsions. Standard drug diazepam
      at a dose of 4 mg/kg showed much delayed onset of clonic seizure. CONCLUSION: The
      study suggests that AEPR would be effective against generalized tonic-clonic and
      partial seizures. Thus AEPR possesses anticonvulsant property against MES- and
      PTZ-induced seizures in Wistar rats. However, further research is in progress to
      isolate the compound responsible for its activity.

PMID- 22979939
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      Diseases in Internal Medicine (Part 5).

PMID- 22979940
TI  - Boron subphthalocyanines as organic electronic materials.
AB  - Boron subphthalocyanines (BsubPcs) are an emerging class of high performing
      materials in organic electronics. Since the first use of chloroboron
      subphthalocyanine in an organic electronic device 6 years ago subphthalocyanines
      have shown potential as functional materials in organic light emitting diodes
      (OLEDs) and organic photovoltaics (OPVs). Here we review the material properties
      of chloroboron subphthalocyanine (Cl-BsubPc) and its use as an organic
      semiconductor. We then highlight our efforts toward derivatives of boron
      subpthalocyanine beyond Cl-BsubPc and discuss the impact of molecular design on
      the material properties and the performance of the BsubPc. Finally, we comment on
      the status of BsubPcs in the field of organic electronics and discuss how we
      believe future progress can be made.

PMID- 22979941
TI  - Effect of methionine on production of naphthoquinones in Impatiens balsamina root
      cultures and detection of some secondary metabolites.
AB  - CONTEXT: Lawsone, lawsone methyl ether and 3,3'-methylelnebislawsone are the main
      active compounds of Impatiens balsamina L. (Balsaminaceae). These compounds
      possess various pharmacological activities that have been shown to assist with
      the treatment of skin diseases. OBJECTIVE: This work focused on increased
      naphthoquinone production in I. basamina root cultures using methionine feeding.
      MATERIALS AND METHODS: I. balsamina root cultures were maintained in liquid
      Gamborg's B5 medium supplemented with 0.1 mg/L alpha-naphthalene acetic acid, 0.1
      mg/L kinetin, 1.0 mg/L 6-benzyladenine and 20 g/L sucrose. The effect of
      methionine concentration (50, 100, 300, 500 and 1000 mg/L) on naphthoquinone
      production of I. basamina root cultures was determined. Isolation of secondary
      metabolites from I. balsamina root cultures was also carried out. RESULTS AND
      DISCUSSION: Feeding of 300 mg/L methionine to the root cultures at the beginning
      of the growth cycle increased the production of 3,3'-methylelnebislawsone almost
      two-fold (0.63 mg/g dry weight, compared to the control group 0.32 mg/g dry
      weight). Optimization of the feeding conditions showed that adding 500 mg/L
      methionine to a 21-day old root cultures increased production of lawsone methyl
      ether and 3,3'-methylenebislawsone up to 2.6- and 3.1-fold higher, respectively,
      compared to the controls. In addition, various pharmacologically interesting
      secondary metabolites were isolated from I. balsamina root cultures, such as a
      flavonoid, luteolin, a naphthoquinone, 2,3-dihydroxy-1,4-naphthoquinone, and a
      triterpenoid, echinocystic acid. This is the first report of the occurrence of
      these compounds in this plant.

PMID- 22979942
TI  - On the origins of lactate during sepsis.
AB  - The origins of sepsis-induced hyperlactatemia are still imperfectly understood
      and probably multifactorial, resulting both from an increased production by
      various tissues through aerobic and anaerobic glycolysis, and from a decreased
      lactate clearance. In the previous issue of Critical Care, Michaeli and
      colleagues showed that lactate elevation during mild endotoxemia is due to an
      increased aerobic production that does not take place in the muscle; other
      tissues/cells may thus be important contributors. 

PMID- 22979943
TI  - Novel human mitochondrial tRNA phe mutation in a patient with hearing impairment:
      a case study.
AB  - We present a patient with non-syndromic and sensorineural hearing impairment with
      a novel mitochondrial DNA transition. A 7-year-old boy showed progressive
      deafness. He gradually lost his hearing ability and his hearing function did not
      improve with hearing aids. Laboratory data revealed normal blood lactate and
      pyruvate levels. Genetic analyses for mitochondrial DNA and GJB2 and GJB6 genes
      were performed. Mitochondrial genes analysis revealed a novel heteroplasmic
      nucleotide substitution, m.628C>T, in the phenylalanine transfer RNA gene. This
      case study reveals m.628C>T transition as a novel mitochondrial nucleotide change
      which may be important in mitochondrial deafness.

PMID- 22979944
TI  - Characterization of GCY1 in Saccharomyces cerevisiae by metabolic profiling.
AB  - AIMS: The analytical study of intracellular (IC) metabolites has developed with
      advances in chromatography-linked mass spectrometry and fast sampling procedures.
      We applied the IC metabolite analysis to characterize the role of GCY1 in the
      glycerol (GLY) catabolic pathway in Saccharomyces cerevisiae. METHODS AND
      RESULTS: Strains with disrupted or overexpressing GLY catabolic genes such as
      GCY1, DAK1 and DAK2 were constructed. The strains were cultivated under different
      aeration conditions and quickly quenched using a novel rapid sampling port. IC
      concentrations of GLY, dihydroxyacetone (DHA), glycerol 3-phosphate and
      dihydroxyacetone phosphate were analysed in the strains by gas
      chromatography/mass spectrometry. DHA was not detected in the gcy1 gene-disrupted
      strain but accumulated 225.91 MUmol g DCW(-1) in a DHA kinase gene-deficient
      strain under micro-aerobic conditions. Additionally, a 16.1% increase in DHA
      occurred by overexpressing GCY1 in the DHA kinase-deficient strain. CONCLUSIONS:
      Metabolic profiling showed that the GCY1 gene product functions as a GLY
      dehydrogenase in S. cerevisiae, particularly under micro-aerobic conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Metabolic profiling of the GLY
      dissimilation pathway was successfully demonstrated in S. cerevisiae, and the
      function of GCY1 was explained by the results.

PMID- 22979945
TI  - Procuring family planning methods for every woman in the world.

PMID- 22979946
TI  - Inhibitory effects of daidzein on intestinal motility in normal and high
      contractile states.
AB  - CONTEXT: Daidzein is a naturally occurring compound and has various health
      benefits. However, its effects on intestinal smooth muscle contractility remain
      unknown. AIMS: The present study was to characterize the effects of daidzein on
      the contractility of isolated jejunal smooth muscle and its underlying
      mechanisms. METHODS: Ex vivo assay was selected as the major method to determine
      the effects of daidzein on the contractility of isolated jejunal smooth muscle
      fragment (JSMF). RESULTS: Daidzein (5-160 umol/L) inhibited the contractility of
      JSMF in normal contractile state and in a dose-dependent manner. Daidzein also
      inhibited the contractility of JSMF induced by ACh, histamine, erythromycin and
      high Ca2+, respectively, and decreased charcoal propulsion in the small intestine
      in vivo. The inhibitory effects of daidzein were partially blocked by
      phentolamine or propranolol and were abolished in the presence of varapamil or at
      Ca2+-free assay condition. However, the inhibitory effects of daidzein on jejunal
      contraction were not significantly influenced by nitric oxide (NO) synthase
      inhibitor L-NG-nitro-arginine (L-NNA). Daidzein was also found to directly
      inhibit the phosphorylation and Mg2+-ATPase activity of smooth muscle myosin.
      DISCUSSION AND CONCLUSION: The results implicated that alpha- and beta-adrenergic
      receptors were involved in the inhibitory effects produced by daidzein rather
      than via NO pathway. As a phytoestrogen, daidzein has shown its potential value
      in relieving the hypercontractility of small intestine.

PMID- 22979948
TI  - Anemia, red blood cell transfusion, and outcomes after severe traumatic brain
      injury.
AB  - In the previous issue of Critical Care, Sekhon and colleagues report that mean 7
      day hemoglobin concentration <90 g/l was associated with increased mortality
      among patients with severe traumatic brain injury (TBI). The adverse relationship
      between reduced hemoglobin concentrations and outcomes among those with TBI has
      been an inconsistent finding across available studies. However, as anemia is
      common among adults with severe TBI, and clinical equipoise may exist between
      specialists as to when to transfuse allogeneic red blood cells, randomized
      controlled trials of liberal versus restricted transfusion thresholds are
      indicated. 

PMID- 22979949
TI  - The microbiology of Bandji, palm wine of Borassus akeassii from Burkina Faso:
      identification and genotypic diversity of yeasts, lactic acid and acetic acid
      bacteria.
AB  - AIM: To investigate physicochemical characteristics and especially genotypic
      diversity of the main culturable micro-organisms involved in fermentation of sap
      from Borassus akeassii, a newly identified palm tree from West Africa. METHODS
      AND RESULTS: Physicochemical characterization was performed using conventional
      methods. Identification of micro-organisms included phenotyping and sequencing
      of: 26S rRNA gene for yeasts, 16S rRNA and gyrB genes for lactic acid bacteria
      (LAB) and acetic acid bacteria (AAB). Interspecies and intraspecies genotypic
      diversities of the micro-organisms were screened respectively by amplification of
      the ITS1-5.8S rDNA-ITS2/16S-23S rDNA ITS regions and repetitive sequence-based
      PCR (rep-PCR). The physicochemical characteristics of samples were: pH: 3.48
      4.12, titratable acidity: 1.67-3.50 mg KOH g(-1), acetic acid: 0.16-0.37%,
      alcohol content: 0.30-2.73%, sugars (degrees Brix): 2.70-8.50. Yeast included
      mainly Saccharomyces cerevisiae and species of the genera Arthroascus,
      Issatchenkia, Candida, Trichosporon, Hanseniaspora, Kodamaea,
      Schizosaccharomyces, Trigonopsis and Galactomyces. Lactobacillus plantarum was
      the predominant LAB species. Three other species of Lactobacillus were also
      identified as well as isolates of Leuconostoc mesenteroides, Fructobacillus
      durionis and Streptococcus mitis. Acetic acid bacteria included nine species of
      the genus Acetobacter with Acetobacter indonesiensis as predominant species. In
      addition, isolates of Gluconobacter oxydans and Gluconacetobacter saccharivorans
      were also identified. Intraspecies diversity was observed for some species of
      micro-organisms including four genotypes for Acet. indonesiensis, three for
      Candida tropicalis and Lactobacillus fermentum and two each for S. cerevisiae,
      Trichosporon asahii, Candida pararugosa and Acetobacter tropicalis. CONCLUSION:
      fermentation of palm sap from B. akeassii involved multi-yeast-LAB-AAB cultures
      at genus, species and intraspecies level. SIGNIFICANCE AND IMPACT OF THE STUDY:
      First study describing microbiological and physicochemical characteristics of
      palm wine from B. akeassii. Genotypic diversity of palm wine LAB and AAB not
      reported before is demonstrated and this constitutes valuable information for
      better understanding of the fermentation which can be used to improve the product
      quality and develop added value by-products.

PMID- 22979947
TI  - Nuclear Factor kappa B is central to Marek's disease herpesvirus induced
      neoplastic transformation of CD30 expressing lymphocytes in-vivo.
AB  - BACKGROUND: Marek's Disease (MD) is a hyperproliferative, lymphomatous,
      neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2
      (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells
      overexpress the CD30 antigen (CD30(hi)) and are in minority, while the non
      neoplastic cells (CD30(lo)) form the majority of population. MD is a unique
      natural in-vivo model of human CD30(hi) lymphomas with both natural CD30(hi)
      lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic
      transformation from CD30(lo) expressing phenotype to CD30(hi) expressing
      neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems
      Biology modeling; we compare the global gene expression of CD30(lo) and CD30(hi)
      cells to identify key pathways of neoplastic transformation. We propose and test
      a specific mechanism of neoplastic transformation, and genetic resistance,
      involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B
      (NF-kappaB) family and CD30; we also identify a novel Meq protein interactome.
      RESULTS: Our results show that a) CD30(lo) lymphocytes are pre-neoplastic
      precursors and not merely reactive lymphocytes; b) multiple transformation
      mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed
      forward cycle that induces CD30 transcription, increases CD30 signaling which
      activates NF-kappaB, and, in turn, increases Meq transcription; d) Meq
      transcriptional repression or activation of the CD30 promoter generally
      correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma
      resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with
      proteins involved in physiological processes central to lymphomagenesis.
      CONCLUSIONS: In the context of the MD lymphoma microenvironment (and potentially
      in other CD30(hi) lymphomas as well), our results show that the neoplastic
      transformation is a continuum and the non-neoplastic cells are actually pre
      neoplastic precursor cells and not merely immune bystanders. We also show that NF
      kappaB is a central player in MDV induced neoplastic transformation of CD30
      expressing lymphocytes in vivo. Our results provide insights into molecular
      mechanisms of neoplastic transformation in MD specifically and also herpesvirus
      induced lymphoma in general.

PMID- 22979950
TI  - Identification of B cell epitopes reactive to human papillomavirus type-16L1-
      derived peptides.
AB  - BACKGROUND: Persistent infection of human papillomavirus (HPV) types 16 and 18
      causes cervical cancer. To better understand immune responses to the prophylactic
      vaccine, HPV 16/18 L1 virus-like particles (HPV-VLPs), we investigated B cell
      epitopes of HPV16 L1-derived peptides. METHODS: Sera from mice immunized with HPV
      16/18 L1 VLPs were analyzed for their IgG titers against 10 different HPV16 L1
      derived peptides (20-mer) that contain human leukocyte antigen (HLA)-class I A-2,
      A-24 and class II DR. RESULTS: One 20-mer peptide at positions 300 to 319 was
      identified as a common B cell epitope in both Balb/c (H-2d) and C57BL/6 (H-2b)
      mice. Mapping analysis showed that the 10-amino-acid sequence at positions 304 to
      313 was an immunogenic portion. It is of note that the binding capability of this
      10-mer peptide to the HLA-A2 and HLA-A24 molecules was confirmed by the HLA class
      I stabilization assay. In addition, one unique 20-mer was determined as a B cell
      epitope in each strain. CONCLUSIONS: These results might provide new information
      for better understanding of immune responses to HPV 16 L1.

PMID- 22979951
TI  - Pharmacological treatments in pathological gambling.
AB  - Pathological gambling (PG) is a relatively common and often disabling psychiatric
      condition characterized by intrusive urges to engage in deleterious gambling
      behaviour. Although common and financially devastating to individuals and
      families, there currently exist no formally approved pharmacotherapeutic
      interventions for this disorder. This review seeks to examine the history of
      medication treatments for PG. A systematic review of the 18 double-blind, placebo
      controlled pharmacotherapy studies conducted for the treatment of pathological
      gambling was conducted. Study outcome and the mean dose of medication
      administered was documented in an effort to determine a preferred medication
      choice in this population. A variety of medication classes have been examined in
      the treatment of PG with varying results. Antidepressants, atypical
      antipsychotics and mood stabilizers have demonstrated mixed results in controlled
      clinical trials. Although limited information is available, opioid antagonists
      and glutamatergic agents have demonstrated efficacious outcomes, especially for
      individuals with PG suffering from intense urges to engage in the behaviour.
      Given that several studies have demonstrated their efficacy in treating the
      symptoms associated with PG, opioid antagonists should be considered the first
      line treatment for PG at this time. Most published studies, however, have
      employed relatively small sample sizes, are of limited duration and involve
      possibly non-representative clinical groups (e.g. those without co-occurring
      psychiatric disorders). Response measures have varied across studies.
      Heterogeneity of PG treatment samples may also complicate identification of
      effective treatments. Identification of factors related to treatment response
      will help inform future studies and advance treatment strategies for PG. 

PMID- 22979953
TI  - Strengthening vasectomy services in Rwanda: introduction of thermal cautery with
      fascial interposition.
AB  - BACKGROUND: Recent developments in vasectomy research indicate that occluding the
      vas using cautery combined with fascial interposition (FI) significantly lowers
      failure rates and is an appropriate technology for low-resource settings. We
      report the introduction of this technique in Ministry of Health (MOH) vasectomy
      services in Rwanda. DESIGN: In February 2010, an international vasectomy expert
      trained three Rwandan physicians to become trainers in no-scalpel vasectomy (NSV)
      with thermal cautery and FI. The training took place over 5 days in five rural
      health centers. RESULTS: A total of 67 men received vasectomies (11-16 per day)
      and trainees successfully mastered the new occlusion technique. The MOH is now
      scaling up NSV with cautery and FI services nationwide. The initial cadre of
      trainers has subsequently trained 46 other physicians in this vasectomy technique
      across 27 districts of Rwanda. CONCLUSIONS: No-scalpel vasectomy with thermal
      cautery and FI was successfully introduced in vasectomy services in Rwanda, and a
      similar initiative should be evaluated in other national vasectomy services
      worldwide.

PMID- 22979952
TI  - FKBP5 and emotional neglect interact to predict individual differences in
      amygdala reactivity.
AB  - Individual variation in physiological responsiveness to stress mediates risk for
      mental illness and is influenced by both experiential and genetic factors. Common
      polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is
      involved in transcriptional regulation of the hypothalamic-pituitary-adrenal
      (HPA) axis, have been shown to interact with childhood abuse and trauma to
      predict stress-related psychopathology. In the current study, we examined if such
      gene-environment interaction effects may be related to variability in the threat
      related reactivity of the amygdala, which plays a critical role in mediating
      physiological and behavioral adaptations to stress including modulation of the
      HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level
      dependent functional magnetic resonance imaging probe of amygdala reactivity and
      self-report assessments of emotional neglect (EN) and other forms of
      maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms
      (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously
      associated with psychopathology and/or HPA axis function. Interactions between
      each SNP and EN emerged such that risk alleles predicted relatively increased
      dorsal amygdala reactivity in the context of higher EN, even after correcting for
      multiple testing. Two different haplotype analyses confirmed this relationship as
      haplotypes with risk alleles also exhibited increased amygdala reactivity in the
      context of higher EN. Our results suggest that increased threat-related amygdala
      reactivity may represent a mechanism linking psychopathology to interactions
      between common genetic variants affecting HPA axis function and childhood trauma.

PMID- 22979954
TI  - Failed IUD insertions in community practice: an under-recognized problem?
AB  - BACKGROUND: The data analysis was conducted to describe the rate of unsuccessful
      copper T380A intrauterine device (IUD) insertions among women using the IUD for
      emergency contraception (EC) at community family planning clinics in Utah.
      METHODS: These data were obtained from a prospective observational trial of women
      choosing the copper T380A IUD for EC. Insertions were performed by nurse
      practitioners at two family planning clinics in order to generalize findings to
      the type of service setting most likely to employ this intervention. Adjuvant
      measures to facilitate difficult IUD insertions (cervical anesthesia, dilation,
      pain medication, and use of ultrasound guidance) were not utilized. The effect of
      parity on IUD insertion success was determined using exact logistic regression
      models adjusted for individual practitioner failure rates. RESULTS: Six providers
      performed 197 IUD insertion attempts. These providers had a mean of 14.1 years of
      experience (range 1-27, S.D. +/-12.5). Among nulliparous women, 27 of 138 (19.6%)
      IUD insertions were unsuccessful. In parous women, 8 of 59 IUD insertions were
      unsuccessful (13.6%). The adjusted odds ratio (aOR) showed that IUD insertion
      failure was more likely in nulliparous women compared to parous women (aOR=2.31,
      95% CI 0.90-6.52, p=.09). CONCLUSION: The high rate of unsuccessful IUD
      insertions reported here, particularly for nulliparous women, suggests that the
      true insertion failure rate of providers who are not employing additional tools
      for difficult insertions may be much higher than reported in clinical trials.
      Further investigation is necessary to determine if this is a common problem and,
      if so, to assess if the use of adjuvant measures will reduce the number of
      unsuccessful IUD insertions.

PMID- 22979955
TI  - Biostimulation to identify microbial communities involved in methane generation
      in shallow, kerogen-rich shales.
AB  - AIMS: The aim of the present study was to design and test a method allowing the
      detection and quantification of methanogenic consortia in organic-rich rocks to
      determine the potential of methane biotransformation. METHODS AND RESULTS:
      Methanogen numbers in the rock are often below the detection levels of
      quantification methods. Biostimulation was tested as a means to specifically
      increase bacterial and archaeal numbers above the detection levels in microcosms.
      Biostimulation reveals the presence of active heterotrophic and syntrophic
      bacterial consortia, methane accumulation and methanogens in one of four rock
      samples. Syntrophs and heterotrophs were dominated by Firmicutes, whereas
      archaeal diversity was limited to methanogens. Methane-producing microcosms were
      characterized by a higher Firmicutes diversity. CONCLUSIONS: Biostimulation is a
      reliable tool for detection of methanogenic consortia in organic-rich rocks. For
      routine and large scale experimentation, methane accumulation monitoring after
      biostimulation appears as the most time, work and cost efficient approach to
      detect the presence of active methanogenic consortia. SIGNIFICANCE AND IMPACT OF
      THE STUDY: We report for the first time the presence of live methanogenic
      consortia in organic-rich shales and their ability to mineralize the rock into
      methane. This approach will be instrumental to quantify the potential of these
      rocks to produce methane as a novel energy source.

PMID- 22979957
TI  - Concerns regarding use of one-tailed tests in the SLED-BD vs. CVVH trial.

PMID- 22979958
TI  - Classic polyarteritis nodosa associated with hepatitis C virus infection: a case
      report.
AB  - INTRODUCTION: Hepatitis C virus has been under-recognized as an etiologic factor
      for polyarteritis nodosa and the presence of hepatitis C antigenemia in patients
      with polyarteritis nodosa has been reported as insignificant. In the literature
      hepatitis C virus-associated polyarteritis nodosa is a rare and controversial
      entity. CASE PRESENTATION: A 34-year-old Sri Lankan Tamil man presented to our
      facility with a two-week history of slow-resolving pneumonia of the right mid and
      lower zones. On physical examination he had panniculitic type tender skin nodules
      with background livedo reticularis. A skin biopsy was suggestive of a small and
      medium vessel vasculitis compatible with polyarteritis nodosa. He was tested
      positive for hepatitis C antibodies. A serum cryoglobulin test was negative but
      perinuclear antineutrophilic cytoplasmic antibody test was positive. Serum
      complement levels were reduced. He was diagnosed as having classic polyarteritis
      nodosa associated with hepatitis C infection. He later developed left-sided
      radiculopathy involving both upper and lower limbs and an ischemic cardiac event.
      His hepatitis C infection was managed with polyethylene glycol-interferon 2alpha
      combined with oral ribavirin. Simultaneously, his classic polyarteritis nodosa
      was treated with prednisolone and cyclophosphamide. He made a good recovery.
      CONCLUSIONS: Hepatitis C virus infection is capable of inducing a fulminant form
      of vasculitis in the form of polyarteritis nodosa. It may be easily confused
      early in its course with mixed cryoglobulinemia, which is commonly known to be
      associated with hepatitis C virus. Awareness of hepatitis C virus-related
      polyarteritis nodosa helps in diagnosing the condition early so combined
      immunosuppressive and antiviral treatment can be started as soon as possible.

PMID- 22979956
TI  - A simple knowledge-based mining method for exploring hidden key molecules in a
      human biomolecular network.
AB  - BACKGROUND: In the functional genomics analysis domain, various methodologies are
      available for interpreting the results produced by high-throughput biological
      experiments. These methods commonly use a list of genes as an analysis input, and
      most of them produce a more complicated list of genes or pathways as the results
      of the analysis. Although there are several network-based methods, which detect
      key nodes in the network, the results tend to include well-studied, major hub
      genes. RESULTS: To mine the molecules that have biological meaning but to fewer
      degrees than major hubs, we propose, in this study, a new network-based method
      for selecting these hidden key molecules based on virtual information flows
      circulating among the input list of genes. The human biomolecular network was
      constructed from the Pathway Commons database, and a calculation method based on
      betweenness centrality was newly developed. We validated the method with the ErbB
      pathway and applied it to practical cancer research data. We were able to confirm
      that the output genes, despite having fewer edges than major hubs, have
      biological meanings that were able to be invoked by the input list of genes.
      CONCLUSIONS: The developed method, named NetHiKe (Network-based Hidden Key
      molecule miner), was able to detect potential key molecules by utilizing the
      human biomolecular network as a knowledge base. Thus, it is hoped that this
      method will enhance the progress of biological data analysis in the whole-genome
      research era.

PMID- 22979959
TI  - Terpenoid biosynthesis in trichomes--current status and future opportunities.
AB  - Glandular trichomes are anatomical structures specialized for the synthesis of
      secreted natural products. In this review we focus on the description of glands
      that accumulate terpenoid essential oils and oleoresins. We also provide an in
      depth account of the current knowledge about the biosynthesis of terpenoids and
      secretion mechanisms in the highly specialized secretory cells of glandular
      trichomes, and highlight the implications for metabolic engineering efforts.

PMID- 22979960
TI  - The canid genome: behavioral geneticists' best friend?
AB  - We review a range of studies on the genetic contribution to behavior in canid
      species. We begin by identifying factors that make canids a promising model in
      behavioral genetics and proceed to review research over the last decade that has
      used canids to identify genetic contributions to behavior. We first review
      studies that have selectively bred dogs to identify genetic contributions to
      behavior and then review studies that estimate heritability from populations of
      non-laboratory bred dogs. We subsequently review studies that used molecular
      genetics to identify gene-behavior associations and note associations that have
      been uncovered. We then note challenges in canid behavioral genetics research
      that require further consideration. We finish by suggesting alternative
      phenotyping methods and identify areas in which canids may have as yet
      unexploited advantages, such as in gene-environment interaction studies where
      genetic factors are found to moderate the effects of environmental variables. 

PMID- 22979961
TI  - Influence of season on corpus luteum structure and function and AI outcome in the
      Italian Mediterranean buffalo (Bubalus bubalis).
AB  - The aim was to ascertain whether relationships between corpus luteum (CL)
      vascularization, CL function, and pregnancy outcome in AI in buffaloes were
      consistent across the breeding season and transition period to the nonbreeding
      season in a Mediterranean environment. Stage of the estrous cycle in Italian
      Mediterranean buffaloes was synchronized using the Ovsynch with timed AI program
      and buffaloes were mated by AI in both the breeding season (N = 131) and
      transition period (N = 125). Detailed investigation of CL structure and function
      was undertaken in 39 buffaloes at each of the respective times using realtime B
      mode/color-Doppler ultrasonography on Days 10 and 20 after AI. Progesterone (P4)
      concentrations were determined by RIA in all buffaloes. Pregnancy rate on Day 45
      after AI was greater (P < 0.05) during the breeding season (58.0%) than the
      transitional period (45.6%) and this was primarily the result of a lower (P <
      0.05) late embryonic mortality during the breeding season (7.3%) compared with
      the transition period (23%). Circulating concentrations of P4 on Days 10 and 20
      after AI were greater (P < 0.01) during the breeding season (4.6 +/- 0.3 and 3.4
      +/- 0.2, respectively) than during the transition period (1.6 +/- 0.12 and 1.8 +/
      0.2, respectively), and this was independent of reproductive status as there was
      no interaction between pregnancy and season. Corpus luteum time average medium
      velocity at Day 10 after AI was greater (P < 0.01) during the breeding season
      (19.3 +/- 1.5) than in the transitional period (8.3 +/- 0.7). There were positive
      correlations in pregnant buffaloes between CL time average medium velocity and P4
      concentrations on Day 10 (r = 0.722; P < 0.01) and Day 20 (r = 0.446; P < 0.01)
      after AI. The findings were interpreted to indicate that relationships between CL
      vascularization, CL function, and pregnancy outcome in AI in buffaloes are
      consistent across the breeding season and transition period to the nonbreeding
      season. The distinction between the breeding season and the transition period is
      the relatively low proportion of buffaloes that have CL function and P4
      concentrations required to establish a pregnancy during the transition period,
      which is manifested in a greater incidence of embryonic mortality.

PMID- 22979962
TI  - Reprogramming mammalian somatic cells.
AB  - Somatic cell nuclear transfer (SCNT), the technique commonly known as cloning,
      permits transformation of a somatic cell into an undifferentiated zygote with the
      potential to develop into a newborn animal (i.e., a clone). In somatic cells,
      chromatin is programmed to repress most genes and express some, depending on the
      tissue. It is evident that the enucleated oocyte provides the environment in
      which embryonic genes in a somatic cell can be expressed. This process is
      controlled by a series of epigenetic modifications, generally referred to as
      "nuclear reprogramming," which are thought to involve the removal of reversible
      epigenetic changes acquired during cell differentiation. A similar process is
      thought to occur by overexpression of key transcription factors to generate
      induced pluripotent stem cells (iPSCs), bypassing the need for SCNT. Despite its
      obvious scientific and medical importance, and the great number of studies
      addressing the subject, the molecular basis of reprogramming in both
      reprogramming strategies is largely unknown. The present review focuses on the
      cellular and molecular events that occur during nuclear reprogramming in the
      context of SCNT and the various approaches currently being used to improve
      nuclear reprogramming. A better understanding of the reprogramming mechanism will
      have a direct impact on the efficiency of current SCNT procedures, as well as
      iPSC derivation.

PMID- 22979963
TI  - Roscovitine is a novel agent that can be used for the activation of porcine
      oocytes reconstructed with adult cutaneous or fetal fibroblast cell nuclei.
AB  - The present study was undertaken to investigate the preimplantation developmental
      competence of cloned pig embryos that were derived from fibroblast cell nuclei by
      different methods for the activation of reconstructed oocytes. In subgroups IA
      and IB, nuclear-transferred (NT) oocytes derived from either adult cutaneous or
      fetal fibroblast cells that had been classified as nonapoptotic by intra vitam
      analysis for programmed cell death using the YO-PRO-1 DNA fluorochrome underwent
      sequential physical (i.e., electrical) and chemical activation (SE-CA). This
      novel method of SE-CA, which was developed and optimized in our laboratory,
      involves treatment of reconstituted oocytes with direct current pulses and
      subsequent exposure to 7.5 MUM calcium ionomycin, followed by incubation with 30
      MUM R-roscovitine (R-RSCV), 0.7 mM 6-dimethylaminopurine and 3.5 MUg/mL
      cycloheximide. In subgroups IIA and IIB, NT oocytes were subjected to the
      standard method of simultaneous fusion and activation mediated by direct current
      pulses. The proportion of cloned embryos in subgroup IA that reached the morula
      and blastocyst stages was 145/248 (58.5%) and 78/248 (31.5%), respectively. The
      proportions of cloned embryos in subgroup IB that reached the morula and
      blastocyst stages were 186/264 (70.5%) and 112/264 (42.4%), respectively. In
      turn, subgroup IIA yielded proportions at the morula and blastocyst stages of
      110/234 (47.0%) and 49/234 (20.9%), respectively. Subgroup IIB yielded
      proportions at the morula and blastocyst stages of 144/243 (59.3%) and 74/243
      (30.5%), respectively. In summary, the SE-CA of NT oocytes reconstructed from
      either type of nonapoptotic/nonnecrotic (i.e., YO-PRO-1-negative) fibroblast cell
      resulted in porcine cloned embryos with considerably better in vitro
      developmental outcomes than those of cloned embryos generated using the
      simultaneous fusion and activation approach. To our knowledge, this is the first
      report of the successful stimulation of porcine NT oocytes using electric pulses
      followed by an additional activation with a higher dose (1.5 times) of calcium
      ionomycin and subsequent exposure to a combination of 30 MUM R-RSCV and lower
      concentrations (by 3 times) of 6-dimethylaminopurine and cycloheximide. Moreover,
      we report here the first use of R-RSCV, a novel meiosis-promoting factor-related
      p34(cdc2) kinase inhibitor, in the oocyte activation protocol for the somatic
      cell cloning of pigs.

PMID- 22979964
TI  - Comparison of the GnRH-stimulation test and a semiquantitative quick test for LH
      to diagnose presence of ovaries in the female domestic cat.
AB  - It is generally recommended that female cats not intended for planned breeding
      are spayed to reduce the population of feral cats and also because spaying is
      beneficial for the long-term health of the individual. For female cats of unknown
      origin or with estrous symptoms after spaying there is a need for a reliable
      method to diagnose or rule out the presence of ovaries to avoid unnecessary
      surgery. Methods previously recommended include vaginal cytology, evaluation of
      serum estradiol concentration during suspected estrus, induction of ovulation and
      subsequent evaluation of progesterone, or explorative laparotomy. These methods
      have the disadvantages that an accurate diagnosis only can be made during estrus
      or that an invasive procedure is required. Previously, the use of a GnRH
      challenge test and a semiquantitative LH test have been reported. Our aim was to
      compare these two methods. We therefore divided 31 female cats in two groups: (1)
      intact nonestrous females (N = 16), and (2) previously ovariohysterectomized
      females (N = 15). A blood sample was collected (Time 0) and 0.4 MUg/kg buserelin
      (Receptal; Intervet, Danderyd, Sweden) was injected im. A new blood sample was
      collected 120 min after the injection. A drop of serum from the sample collected
      at Time 0 was placed on the LH test (Witness LH; Synbiotics, Corp., San Diego,
      CA, USA) and the result was evaluated as negative or positive. The remaining
      serum was frozen and analyzed for estradiol in one batch. Serum estradiol before
      buserelin stimulation ranged between 5 and 45 pmol/L (N = 14) in intact
      nonestrous queens and between 2 and 6 pmol/L (N = 15) in ovariohysterectomized
      females. Estradiol in samples collected after 120 min ranged between 12 and 51
      pmol/L (N = 16) in intact queens and between 1 and 7 pmol/L (N = 15) in spayed
      cats giving a sensitivity and specificity of 100% for the buserelin stimulation
      test at a cutoff value of 11 pmol/L. All intact queens were negative in the
      semiquantitative LH test while 14/15 spayed cats were positive and one was
      negative giving a sensitivity of 100% and a specificity of 93.8% to detect the
      presence of ovaries in nonestrous cats.

PMID- 22979965
TI  - Donkey jack (Equus asinus) semen cryopreservation: studies of seminal parameters,
      post breeding inflammatory response, and fertility in donkey jennies.
AB  - The aims of this study were (1) to evaluate motility parameters of donkey jack
      (jack; Equus asinus) semen cryopreserved in INRA-96 (INRA; IMV Technologies,
      France, 2% egg-yolk enriched) using either glycerol (GLY) or ethylene glycol (EG)
      as a cryoprotector; (2) to compare in vitro the postthaw re-extension with
      homologous seminal plasma (SPL) or INRA; (3) to compare fertility in donkey
      jennies (jennies; Equus asinus) timed artificially inseminated with jack semen
      cryopreserved using GLY or EG, re-extended with INRA; (4) to compare fertility in
      jennies timed artificially inseminated with jack semen cryopreserved using GLY re
      extended with SPL, INRA, or not re-extended (NN); and (5) to describe some
      preliminary results of the inflammatory uterine response postbreeding. Semen from
      two jacks was collected and frozen in an INRA-2% egg yolk extender added of
      either 2.2% GLY or 1.4% EG. Postthaw motility was evaluated by a computer
      assisted motility analyzer. Uterine inflammatory response and fertility were
      evaluated after artificial insemination (AI) of 13 jennies with frozen-thawed
      semen, either further extended with INRA (Group GLY-INRA, 13 cycles, and EG-INRA,
      8 cycles), or with SPL (Group GLY-SPL, 13 cycles), or not re-extended (GLY-NN, 5
      cycles). In each cycle, jennies were bred twice with 500 * 10(6) sperm cells (250
      * 10(6) from each jack), at fixed times after induction of ovulation, and uterus
      was flushed at 6 and 10 h after first and second breeding, respectively. Cells in
      the recovered fluid were counted and distinguished as polymorphonuclear
      neutrophils (PMN) or other cell types. Total and progressive motility did not
      differ between cryoprotectants, but were higher when semen samples were re
      extended in INRA, compared with SPL (P < 0.05). Pregnancy was diagnosed by
      transrectal palpation and ultrasonography examinations at 14 and 16 days
      postovulation. In 7/13 (53.8%) jennies and 12/39 (30.4%) cycles postbreeding
      intrauterine fluid accumulation was observed, with no differences between
      treatments (P < 0.05). Polymorphonuclear neutrophil numbers and concentrations
      were higher in the first flushing compared with the second, and PMN concentration
      was higher in GLY-SPL than in GLY-INRA (P < 0.05). Pregnancy rates in GLY-SPL,
      GLY-INRA, EG-INRA, and GLY-NN were 8/13, 3/13, 2/8, and 1/5, respectively. There
      was no significant difference either between the two cryoprotectants re-extended
      in INRA, or between re-extension groups. There was however a trend for GLY-SPL to
      improve pregnancy rates compared with GLY-INRA (P = 0.055). These results
      indicate that it is possible to obtain similar postthaw sperm motility and
      pregnancy rates using GLY or EG as a cryoprotectant for donkey semen, and that in
      the conditions of this study the re-extension in SPL of thawed semen before AI
      showed a trend toward the improvement of fertility and increased PMN
      concentration in uterine flushings.

PMID- 22979969
TI  - Herd-level prevalence of Mycobacterium avium subsp. paratuberculosis infection in
      United States dairy herds in 2007.
AB  - Testing of composite fecal (environmental) samples from high traffic areas in
      dairy herds has been shown to be a cost-effective and sensitive method for
      classification of herd status for Mycobacterium avium subsp. paratuberculosis
      (MAP). In the National Animal Health Monitoring System's (NAHMS) Dairy 2007
      study, the apparent herd-level prevalence of MAP was 70.4% (369/524 had >= 1
      culture-positive composite fecal samples out of 6 tested). Based on these data,
      the true herd-level prevalence (HP) of MAP infection was estimated using Bayesian
      methods adjusting for the herd sensitivity (HSe) and herd specificity (HSp) of
      the test method. The Bayesian prior for HSe of composite fecal cultures was based
      on data from the NAHMS Dairy 2002 study and the prior for HSp was based on expert
      opinion. The posterior median HP (base model) was 91.1% (95% probability
      interval, 81.6 to 99.3%) and estimates were most sensitive to the prior for HSe.
      The HP was higher than estimated from the NAHMS Dairy 1996 and 2002 studies but
      estimates are not directly comparable with those of prior NAHMS studies because
      of the different testing methods and criteria used for herd classification.

PMID- 22979971
TI  - Vitamin D supplementation for the prevention of pre-eclampsia? 'First do no
      harm'.

PMID- 22979972
TI  - A clinical prediction model to assess the risk of operative delivery.

PMID- 22979977
TI  - Vigabatrin-related magnetic resonance imaging abnormalities in an infant with
      tuberous sclerosis complex and infantile spasms.

PMID- 22979978
TI  - Not all twitching is epileptic! Hand myoclonus in a boy with spinal cord tumor.

PMID- 22979979
TI  - Dynamics of p53 and NF-kappaB regulation in response to DNA damage and
      identification of target proteins suitable for therapeutic intervention.
AB  - BACKGROUND: The genome is continuously attacked by a variety of agents that cause
      DNA damage. Recognition of DNA lesions activates the cellular DNA damage response
      (DDR), which comprises a network of signal transduction pathways to maintain
      genome integrity. In response to severe DNA damage, cells undergo apoptosis to
      avoid transformation into tumour cells, or alternatively, the cells enter
      permanent cell cycle arrest, called senescence. Most tumour cells have defects in
      pathways leading to DNA repair or apoptosis. In addition, apoptosis could be
      counteracted by nuclear factor kappa B (NF-kappaB), the main anti-apoptotic
      transcription factor in the DDR. Despite the high clinical relevance, the
      interplay of the DDR pathways is poorly understood. For therapeutic purposes DNA
      damage signalling processes are induced to induce apoptosis in tumour cells.
      However, the efficiency of radio- and chemotherapy is strongly hampered by cell
      survival pathways in tumour cells. In this study logical modelling was performed
      to facilitate understanding of the complexity of the signal transduction networks
      in the DDR and to provide cancer treatment options. RESULTS: Our comprehensive
      discrete logical model provided new insights into the dynamics of the DDR in
      human epithelial tumours. We identified new mechanisms by which the cell
      regulates the dynamics of the activation of the tumour suppressor p53 and NF
      kappaB. Simulating therapeutic intervention by agents causing DNA single-strand
      breaks (SSBs) or DNA double-strand breaks (DSBs) we identified candidate target
      proteins for sensitization of carcinomas to therapeutic intervention. Further, we
      enlightened the DDR in different genetic diseases, and by failure mode analysis
      we defined molecular defects putatively contributing to carcinogenesis.
      CONCLUSION: By logic modelling we identified candidate target proteins that could
      be suitable for radio- and chemotherapy, and contributes to the design of more
      effective therapies.

PMID- 22979980
TI  - Affinity for, and localization of, PEG-functionalized silica nanoparticles to
      sites of damage in an ex vivo spinal cord injury model.
AB  - BACKGROUND: Traumatic spinal cord injury (SCI) leads to serious neurological and
      functional deficits through a chain of pathophysiological events. At the
      molecular level, progressive damage is initially revealed by collapse of plasma
      membrane organization and integrity produced by breaches. Consequently, the loss
      of its role as a semi-permeable barrier that generally mediates the regulation
      and transport of ions and molecules eventually results in cell death. In previous
      studies, we have demonstrated the functional recovery of compromised plasma
      membranes can be induced by the application of the hydrophilic polymer
      polyethylene glycol (PEG) after both spinal and brain trauma in adult rats and
      guinea pigs. Additionally, efforts have been directed towards a nanoparticle
      based PEG application.The in vivo and ex vivo applications of PEG-decorated
      silica nanoparticles following CNS injury were able to effectively and
      efficiently enhance resealing of damaged cell membranes. RESULTS: The possibility
      for selectivity of tetramethyl rhodamine-dextran (TMR) dye-doped, PEG
      functionalized silica nanoparticles (TMR-PSiNPs) to damaged spinal cord was
      evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged
      spinal cord tissues exhibited an obvious difference in both the imbibement and
      accumulation of the TMR-PSiNPs, revealing selective labeling of compression
      injured tissues. CONCLUSIONS: These data show that appropriately functionalized
      nanoparticles can be an efficient means to both 1.) carry drugs, and 2.) apply
      membrane repair agents where they are needed in focally damaged nervous tissue.

PMID- 22979981
TI  - Plant virus expression vectors set the stage as production platforms for
      biopharmaceutical proteins.
AB  - Transgenic plants present enormous potential as a cost-effective and safe
      platform for large-scale production of vaccines and other therapeutic proteins. A
      number of different technologies are under development for the production of
      pharmaceutical proteins from plant tissues. One method used to express high
      levels of protein in plants involves the employment of plant virus expression
      vectors. Plant virus vectors have been designed to carry vaccine epitopes as well
      as full therapeutic proteins such as monoclonal antibodies in plant tissue both
      safely and effectively. Biopharmaceuticals such as these offer enormous potential
      on many levels, from providing relief to those who have little access to modern
      medicine, to playing an active role in the battle against cancer. This review
      describes the current design and status of plant virus expression vectors used as
      production platforms for biopharmaceutical proteins.

PMID- 22979982
TI  - Comparison of the effect of aspirin and amantadine for the treatment of fatigue
      in multiple sclerosis: a randomized, blinded, crossover study.
AB  - OBJECTIVES: The purpose of this study was to compare the relative efficacy of
      acetylsalicylic acid (ASA) and amantadine for the treatment of fatigue in
      multiple sclerosis (MS). METHODS: A 10-week, randomized double-blind crossover
      clinical trial conducted from October  2009 to September 2010. Fifty-two patients
      with MS presenting fatigue at 21 to 53 years of age were randomly allocated to
      the two treatment groups. The first group received amantadine (100 mg twice
      daily) for a total of 4 weeks. The second group received ASA (500 mg once daily)
      for four weeks.  After a 2-week washout period, they crossed over to the
      alternative treatment for 4 weeks. Patients were rated at baseline and the end of
      each phase with the Fatigue Severity Scale (FSS). RESULTS: ASA appeared to be
      equivalent in efficacy and safety to amantadine. A significant decrease  in FSS
      occurred in both groups. Of the 26 patients treated with amantadine, the mean
      (SD) of FSS decreased from 4.8 (1.4) to 4.0 (1.4) (P<0.001). In the 26 patients
      treated with ASA, the mean (SD) of FSS decreased from 4.6 (1.4) to  3.5 (1.5)
      (P<0.001). DISCUSSION: This study demonstrates that both ASA and amantadine
      significantly reduce MS-related fatigue. Both ASA and amantadine have previously
      been shown to reduce fatigue, and we postulate that treatment with ASA and
      amantadine  may have similar benefits.

PMID- 22979983
TI  - The crystal structure of galactitol-1-phosphate 5-dehydrogenase from Escherichia
      coli K12 provides insights into its anomalous behavior on IMAC processes.
AB  - Endogenous galactitol-1-phosphate 5-dehydrogenase (GPDH) (EC 1.1.1.251) from
      Escherichia coli spontaneously interacts with Ni(2+)-NTA matrices becoming a
      potential contaminant for recombinant, target His-tagged proteins. Purified
      recombinant, untagged GPDH (rGPDH) converted galactitol into tagatose, and d
      tagatose-6-phosphate into galactitol-1-phosphate, in a Zn(2+)- and NAD(H)
      dependent manner and readily crystallized what has permitted to solve its crystal
      structure. In contrast, N-terminally His-tagged GPDH was marginally stable and
      readily aggregated. The structure of rGPDH revealed metal-binding sites
      characteristic from the medium-chain dehydrogenase/reductase protein superfamily
      which may explain its ability to interact with immobilized metals. The structure
      also provides clues on the harmful effects of the N-terminal His-tag.

PMID- 22979984
TI  - A conserved regulatory element located far downstream of the gls locus modulates
      gls expression through chromatin loop formation during myogenesis.
AB  - Chromatin loops formed between distant regulatory elements and promoters modulate
      gene expression. We identified a novel distant regulatory element located
      approximately 120kb downstream of the gls promoter, and examined its regulatory
      relevance to gls gene expression in C2C12 cells by a chromosome conformation
      capture assay. The distant element physically interacted with the gls promoter in
      myoblasts but not in myotubes. Semiquantitative analysis by real-time PCR showed
      more abundant gls transcripts in myoblasts than in myotubes. These findings
      suggest that this distant element differentially regulates gls gene expression
      through dynamic formation and abrogation of a chromatin loop during myogenesis.

PMID- 22979989
TI  - The promotion of HL-1 cardiomyocyte beating using anisotropic collagen-GAG
      scaffolds.
AB  - Biomaterials for myocardial tissue engineering must balance structural,
      mechanical and bioactivity concerns. This work describes the interaction between
      HL-1 cardiomyocytes and a series of geometrically anisotropic collagen-GAG (CG)
      scaffolds with aligned tracks of ellipsoidal pores designed to mimic elements of
      the native geometric anisotropy of cardiac tissue. Here we report the role
      scaffold geometric anisotropy and pore size plays in directing cardiomyocyte
      bioactivity. Notably, HL-1 cardiomyocytes showed good proliferation and metabolic
      activity in all variants out to 14 days in culture. Critically, HL-1s exhibited
      significantly elevated 3D alignment and earlier spontaneous beating within
      anisotropic CG scaffolds relative to isotropic scaffold controls. This
      spontaneous beating occurred at significantly higher instances for larger pore
      size anisotropic variants. Gene expression and immunohistochemical analyses for
      key cardiac marker (alpha-myosin heavy chain, connexin-43) suggest that the
      isotropic and anisotropic scaffolds support expression of key transcriptomic
      markers of cardiomyocyte phenotype as well as the formation of gap junctions and
      elongated, aligned cell morphologies. Collectively, these results suggest that a
      geometrically anisotropic scaffold with sufficiently large pore size (>150 MUm)
      provides a suitable microenvironment to induce cardiomyocyte alignment, beating,
      and bioactivity for cardiac tissue engineering applications.

PMID- 22979988
TI  - Effect of modulating macrophage phenotype on peripheral nerve repair.
AB  - Peripheral nerve repair across long gaps remains clinically challenging despite
      progress made with autograft transplantation. While scaffolds that present
      trophic factors and extracellular matrix molecules have been designed, matching
      the performance of autograft-induced repair has been challenging. In this study,
      we explored the effect of cytokine mediated 'biasing' of macrophage phenotypes on
      Schwann cell (SC) migration and axonal regeneration in vitro and in vivo.
      Macrophage phenotype was successfully modulated by local delivery of either
      Interferon-gamma (IFN-gamma) or Interleukin-4 (IL-4) within polymeric nerve
      guidance channels, polarizing them toward pro-inflammatory (M1) or pro-healing
      (M2a and M2c) phenotypes, respectively. The initial polarization of macrophages
      to M2a and M2c phenotype results in enhanced SC infiltration and substantially
      faster axonal growth in a critically-sized rat sciatic nerve gap model (15 mm).
      The ratio of pro-healing to pro-inflammatory population of macrophages
      (CD206+/CCR7+), defined as regenerative bias, demonstrates a linear relationship
      with the number of axons at the distal end of the nerve scaffolds. The present
      results clearly suggest that rather than the extent of macrophage presence, their
      specific phenotype at the site of injury regulates the regenerative outcomes.

PMID- 22979990
TI  - A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery
      for tumor gene therapy.
AB  - RNA interference holds tremendous potential as a therapeutic approach of
      malignant tumors. However, safe and efficient nanovectors are extremely lack for
      systemic delivery of small interfering RNA (siRNA). The study aimed to develop a
      biomimetic nanovector, reconstituted high density lipoprotein (rHDL), mediating
      targeted cholesterol-conjugated siRNA (Chol-siRNA) delivery for Pokemon gene
      silencing therapy. Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA
      complexes) were prepared using thin-film dispersion method and their
      characteristics were investigated in detail. RHDL/Chol-siRNA complexes at the
      optimal volume ratio (lipid: Chol-siRNA) exhibited high Chol-siRNA-loading
      efficiency (~99%), desirable nanoparticle size and excellent stability in serum.
      In addition, by analyzing Chol-siRNA release profile, rHDL/Chol-siRNA complexes
      displayed sustained-release characteristic and storage stability. Observations
      from FACS and confocal microscopic analyses revealed that rHDL-mediated
      carboxyfluorescein tagged Chol-siRNA (FAM-Chol-siRNA) transfection resulted in
      highly efficient uptake and specific cytoplasmic delivery of FAM-Chol-siRNA into
      human hepatocellular carcinoma cell line HepG2 via HDL-receptor mediated
      mechanism. In vitro cytotoxicity, apoptosis and Western-blot analyses revealed
      significant cellular growth inhibition and decrease of Pokemon and Bcl-2 protein
      expression in HepG2 cells treated with Chol-siRNA-Pokemon-loaded rHDL
      nanoparticles (rHDL/Chol-siRNA-Pokemon complexes), respectively. In in vivo
      studies, the near-infrared (NIR) dye Cy5 labeled Chol-siRNA-loaded rHDL
      nanoparticles (rHDL/Cy5-Chol-siRNA complexes) obviously accumulated in tumor of
      nude mice after i.v. administration as compared with Cy5-Chol-siRNA-loaded
      lipoplexes (Lipos/Cy5-Chol-siRNA complexes). Morover, rHDL/Chol-siRNA-Pokemon
      complexes demonstrated great tumor growth inhibition and significant decrease of
      Pokemon and Bcl-2 protein expression in vivo. These results suggested that rHDL
      should be an ideal non-viral tumor-targeting vector for Chol-siRNA transfer, and
      rHDL-mediated Chol-siRNA-Pokemon delivery might be a promising new strategy for
      gene therapy in hepatocellular carcinoma.

PMID- 22979992
TI  - Cannabidiol blocks long-lasting behavioral consequences of predator threat
      stress: possible involvement of 5HT1A receptors.
AB  - Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a
      traumatic experience. Predator exposure promotes long-lasting anxiogenic effect
      in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol
      (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic
      effects. The present study investigated the anti-anxiety actions of CBD
      administration in a model of PTSD. Male Wistar rats exposed to a predator (cat)
      received, 1 h later, singled or repeated i.p. administration of vehicle or CBD.
      Seven days after the stress animals were submitted to the elevated plus maze. To
      investigate the involvement of 5HT1A receptors in CBD effects animals were pre
      treated with WAY100635, a 5HT1A receptor antagonist. To explore possible
      neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and
      BDNF protein expression were measured in the hippocampus, frontal cortex,
      amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD
      prevented long-lasting anxiogenic effects promoted by a single predator exposure.
      Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator
      exposure 5HT1A mRNA expression was up regulated in the frontal cortex and
      hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF
      expression was found. In conclusion, predator exposure promotes long-lasting up
      regulation of 5HT1A receptor gene expression in the hippocampus and frontal
      cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects
      observed after predator exposure probably by facilitating 5HT1A receptors
      neurotransmission. Our results suggest that CBD has beneficial potential for PTSD
      treatment and that 5HT1A receptors could be a therapeutic target in this
      disorder.

PMID- 22979993
TI  - Functional milestones and clinician ratings of everyday functioning in people
      with schizophrenia: overlap between milestones and specificity of ratings.
AB  - Everyday functioning is known to be impaired in people with schizophrenia, across
      multiple functional domains. It is not clear, however, how impairments across
      social, vocational, and residential domains overlap with each other, Further,
      although there are multiple ratings scales available to rate everyday
      functioning, it is also not clear how scores on these scales, particularly total
      scores, relate to milestone achievement. This is important, because efforts to
      reduce disability with pharmacological or rehabilitative interventions are
      ultimately evaluated in terms of their impact on everyday functioning, which is
      often indexed with total scores on rating scales. In this paper from the VALERO
      study, we report on 195 people with schizophrenia who were rated with a
      comprehensive process on 6 different functional status rating scales. Milestone
      achievements in social (ever married or equivalent), vocational (ever employed,
      currently employed), and residential (living independently, financially
      responsible) domains were examined for their overlap with each other and with
      ratings on the rating scales. Total scores on the 6 rating scales were minimally
      related to milestone achievements and milestone achievements were quite
      independent of each other. Subscales from two of the rating scales, specifically
      examining vocational and residential functioning, were specifically related to
      milestone achievements in their functional domains, but not other milestones.
      These data suggest that global scores on everyday functioning measures may not
      capture functional milestones and highlight the fact that functional milestones
      have multiple determinants other then the ability variables that these rating
      scales attempt to capture.

PMID- 22979994
TI  - Further evidence that pediatric-onset bipolar disorder comorbid with ADHD
      represents a distinct subtype: results from a large controlled family study.
AB  - We used familial risk analysis to clarify the diagnostic comorbidity between
      pediatric BP-I disorder and ADHD, testing the hypothesis that pediatric-BP-I
      disorder comorbid with ADHD represents a distinct subtype. Structured diagnostic
      interviews were used to obtain DSM-IV psychiatric diagnoses on first-degree
      relatives (n = 726) of referred children and adolescents satisfying diagnostic
      criteria for BP-I disorder (n = 239). For comparison, diagnostic information on
      the first-degree relatives (N = 511) of non-bipolar ADHD children (N = 162) and
      the first degree relatives (N = 411) of control children (N = 136) with neither
      ADHD nor BP-I disorder were examined. BP-I disorder and ADHD in probands bred
      true irrespective of the comorbidity with the other disorder. We also found that
      the comorbid condition of BP-I disorder plus ADHD also bred true in families, and
      the two disorders co-segregated among relatives. This large familial risk
      analysis provides compelling evidence that pediatric BP-I disorder comorbid with
      ADHD represents a distinct familial subtype.

PMID- 22979995
TI  - Wiring diagrams in biology: towards the standardized representation of biological
      information.

PMID- 22979997
TI  - A multidimensional matrix for systems biology research and its application to
      interaction networks.
AB  - A multidimensional matrix containing 76 parameters from 21 transcriptomics,
      proteomics, interactomics, phenotypic and sequence-based data sets, in which each
      data set covered most of the  Saccharomyces cerevisiae  proteome, was compiled
      for systems biology research. The maximal information coefficient (MIC) was used
      to measure correlations between every pair of parameters. Out of 2850 possible
      comparisons, 340 pairs of variables (12%) showed statistically significant MIC
      scores. There were 321 relationships that were expected; these included
      relationships within physicochemical parameters of proteins, between abundance
      levels of genes/proteins and expression noise, and between different types of
      intracellular networks. We found 19 potentially novel relationships between
      different types of "-omics" data. The strongest of these involved genetic
      interaction networks, which were correlated with pleiotropy and cell-to-cell
      variability in protein expression. Protein disorder also showed a number of
      significant relationships with protein abundance, signaling and regulatory
      networks. Significant cross-talk was seen between the signaling and kinase
      interaction networks. Investigation of this revealed densely connected kinase
      clusters and significant signaling between them, along with signaling centers
      that act as integrators or broadcasters of intracellular information. These
      centers may allow for redundancy and a means of dampening noise in networks under
      a variety of genetic or environmental perturbations.

PMID- 22979998
TI  - Array comparative genomic hybridization in prenatal diagnosis of first trimester
      pregnancies at high risk for chromosomal anomalies.
AB  - OBJECTIVE: To describe the diagnostic performance of array comparative genomic
      hybridization (aCGH) as a potential first line diagnostic method in first
      trimester high risk pregnancies. METHOD: In a retrospective study we performed
      aCGH using a targeted array BAC platform (Constitutional Chip(r) 4.0,
      PerkinElmer, Turku Finland, median resolution 600 kB) and the Affymetrix
      Cytogenetics(r) Whole Genome 2.7 M array (at a resolution of 400kB) on 100
      anonymized prenatal samples from first trimester high risk pregnancies with
      normal conventional karyotype. We studied the technical feasibility and turn
      around-time as well as the detection rate of pathogenic submicroscopic chromosome
      anomalies and CNVs of unknown significance. RESULTS: We obtained results in 98 of
      100 samples in 3 to a maximum of 5 days after DNA extraction. At the given
      resolution we did not identify any additional pathogenic CNVs but two CNVs of
      unknown significance in the chromosomal regions 1q21.1q21.2 (deletion) and
      5p15.33 (duplication) (2%). CONCLUSION: In accordance with a growing number of
      reports this study supports the concept that aCGH at a resolution of 400-600kB
      may be used as a first line prenatal diagnostic test with high diagnostic safety
      and rapid turn-around time in high-risk first trimester pregnancies. Detection
      rate of CNVs of unknown significance, considered as a major hindrance for
      replacing conventional karyotyping by aCGH, is 2%, but the diagnosis of
      additional submicroscopic anomalies in this heterogeneous group of patients seems
      to be rare.

PMID- 22980000
TI  - Quantitative transfer of Escherichia coli O157:H7 to equipment during small-scale
      production of fresh-cut leafy greens.
AB  - Postharvest contamination and subsequent spread of Escherichia coli O157:H7 can
      occur during shredding, conveying, fluming, and dewatering of fresh-cut leafy
      greens. This study quantified E. coli O157:H7 transfer from leafy greens to
      equipment surfaces during simulated  small-scale commercial processing. Three to
      five batches (22.7 kg) of baby spinach, iceberg lettuce, and romaine lettuce were
      dip inoculated with a four-strain cocktail of avirulent, green fluorescent
      protein-labeled, ampicillinresistant E. coli O157:H7 to contain ~10(6),  10(4),
      and 10(2) CFU/g, and then were processed after 1 h of draining at ~23 degrees C
      or 24 h of storage at 4 degrees C. Lettuce was shredded using an Urschel
      TransSlicer at two different blade and belt speeds to obtain normal (5 by 5 cm)
      and more finely shredded (0.5 by 5 cm)  lettuce. Thereafter, the lettuce was step
      conveyed to a flume tank and was washed and then dried using a shaker table and
      centrifugal dryer. Product (25-g) and water (40-ml) samples were collected at
      various points during processing. After processing, product contact surfaces (100
      cm(2))  on the shredder (n = 14), conveyer (n = 8), flume tank (n = 11), shaker
      table (n = 9), and centrifugal dryer (n = 8) were sampled using one-ply composite
      tissues. Sample homogenates diluted in phosphate or neutralizing buffer were
      plated, with or without  prior 0.45- m m membrane filtration, on Trypticase soy
      agar containing 0.6% yeast extract supplemented with 100 ppm of ampicillin to
      quantify green fluorescent protein-labeled E. coli O157:H7 under UV light. During
      leafy green processing, ~90% of the E. coli O157:H7  inoculum transferred to the
      wash water. After processing, E. coli O157:H7 populations were highest on the
      conveyor and shredder (P<0.05), followed by the centrifugal dryer, flume tank,
      and shaker table, with ~29% of the remaining product inoculum lost during
      centrifugal  drying. Overall, less (P<0.05) of the inoculum remained on the
      product after centrifugally drying iceberg lettuce that was held for 1 h (8.13%)
      as opposed to 24 h (42.18%) before processing, with shred size not affecting the
      rate of E. coli O157:H7 transfer.

PMID- 22980001
TI  - Efficacy of UV, acidified sodium hypochlorite, and mild heat for decontamination
      of surface and infiltrated Escherichia coli O157:H7 on green onions and baby
      spinach.
AB  - Produce-associated foodborne illnesses outbreaks have highlighted the need for
      more effective decontamination methods to ensure the safety of fresh produce. The
      main objective of this study was to evaluate the individual and combined
      efficacies of germicidal UV light (12.5 to 500 mJ/cm(2)),  acidified sodium
      hypochlorite (ASC 10 to 200 ppm), and mild heat (40 to 50 degrees C) for
      decontaminating green onions and baby spinach infected with Escherichia coli
      O157:H7. Samples were inoculated by spot and dip inoculation methods to mimic
      surface and infiltrated E. coli O157:H7  contamination, respectively. In green
      onions and baby spinach, the individual efficacies of UV, ASC, and mild-heat
      treatments varied based on the produce type and contamination method. Following
      analysis of the efficacies of the single treatments, a combined treatment with
      125 mJ/cm(2)  UV and 200 ppm of ASC at 50 degrees C was selected for spot
      inoculated green onions, and a combined treatment with 125 mJ/cm(2) UV and 200
      ppm of ASC at 20 degrees C was selected for spot- and dip-inoculated baby
      spinach. While a >5-log reduction was achieved with the combination treatment 
      for spot-inoculated green onions with an initial contamination level of 7.2 log
      CFU per spot, the same treatment reduced E. coli O157:H7 populations below the
      detection limit (<1 log) on green onions spot inoculated at a lower contamination
      level (4.3 log CFU per spot). On spot-  and dip-inoculated baby spinach, the
      combined treatment reduced E. coli O157:H7 populations by 2.8 log CFU per spot
      and 2.6 log CFU/g, respectively. The combined treatment of 500 mJ/cm(2) UV and
      200 ppm of ASC at 50 degrees C selected for the decontamination of dip-inoculated
      green  onions resulted in a 2.2-log CFU/g reduction. These findings suggest that
      when foodborne pathogens contaminate produce and subsequently infiltrate, attach
      to, or become localized into protected areas, the individual or combined
      applications of UV, ASC, and mild-heat treatments have limited  decontamination
      efficacies on both green onions and baby spinach (<3 log). However, treatments
      combining UV, ASC, and mild heat could be a promising application for reducing
      pathogen populations (>5 log) on E. coli O157:H7 surface-contaminated green
      onions. This study also highlights  the importance of developing and optimizing
      produce-specific decontamination methods to ensure the safety of fresh produce
      commodities.

PMID- 22980002
TI  - Evaluation of commonly used antimicrobial interventions for fresh beef inoculated
      with Shiga toxin-producing Escherichia coli serotypes O26, O45, O103, O111, O121,
      O145, and O157:H7.
AB  - Although numerous antimicrobial interventions targeting Escherichia coli O157:H7
      have been developed and implemented to decontaminate meat and meat products
      during the harvesting process, the information on efficacy of these interventions
      against the so-called Big Six non-O157  Shiga toxin-producing E. coli (STEC)
      strains is limited. Prerigor beef flanks (160) were inoculated to determine if
      antimicrobial interventions currently used by the meat industry have a similar
      effect in reducing non-O157 STEC serogroups O26, O45, O103, O111, O121, and O145
      compared  with E. coli O157:H7. A high (10(4) CFU/cm(2)) or a low (10(1)
      CFU/cm(2)) inoculation of two cocktail mixtures was applied to surfaces of fresh
      beef. Cocktail mixture 1 was composed of O26, O103, O111, O145, and O157, while
      cocktail mixture 2 was  composed of O45, O121, and O157. The inoculated fresh
      beef flanks were subjected to spray treatments by the following four
      antimicrobial compounds: acidified sodium chlorite, peroxyacetic acid, lactic
      acid, and hot water. High-level inoculation samples were enumerated for the
      remaining bacteria  populations after each treatment and compared with the
      untreated controls, while low-level inoculation samples were chilled for 48 h at
      4 degrees C before enrichment, immunomagnetic separation, and isolation. Spray
      treatments with hot water were the most effective, resulting in mean pathogen
      reductions  of 3.2 to 4.2 log CFU/cm(2), followed by lactic acid. Hot water and
      lactic acid also were the most effective interventions with the low-level
      inoculation on surfaces of fresh beef flanks after chilling. Peroxyacetic acid
      had an intermediate effect, while acidified sodium chlorite  was the least
      effective in reducing STEC levels immediately after treatment. Results indicate
      that the reduction of non-O157 STEC by antimicrobial interventions on fresh beef
      surfaces were at least as great as for E. coli O157:H7. However, the recovery of
      these low inoculation levels  of pathogens indicated that there is no single
      intervention to eliminate them.

PMID- 22979996
TI  - Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis.
AB  - The gut-brain axis refers to the bidirectional communication between the gut and
      the brain. Four information carriers (vagal and spinal afferent neurons, immune
      mediators such as cytokines, gut hormones and gut microbiota-derived signalling
      molecules) transmit information from the gut to the brain, while autonomic
      neurons and neuroendocrine factors carry outputs from the brain to the gut. The
      members of the neuropeptide Y (NPY) family of biologically active peptides, NPY,
      peptide YY (PYY) and pancreatic polypeptide (PP), are expressed by cell systems
      at distinct levels of the gut-brain axis. PYY and PP are exclusively expressed by
      endocrine cells of the digestive system, whereas NPY is found at all levels of
      the gut-brain and brain-gut axis. The major systems expressing NPY comprise
      enteric neurons, primary afferent neurons, several neuronal pathways throughout
      the brain and sympathetic neurons. In the digestive tract, NPY and PYY inhibit
      gastrointestinal motility and electrolyte secretion and in this way modify the
      input to the brain. PYY is also influenced by the intestinal microbiota, and NPY
      exerts, via stimulation of Y1 receptors, a proinflammatory action. Furthermore,
      the NPY system protects against distinct behavioural disturbances caused by
      peripheral immune challenge, ameliorating the acute sickness response and
      preventing long-term depression. At the level of the afferent system, NPY
      inhibits nociceptive input from the periphery to the spinal cord and brainstem.
      In the brain, NPY and its receptors (Y1, Y2, Y4, Y5) play important roles in
      regulating food intake, energy homeostasis, anxiety, mood and stress resilience.
      In addition, PP and PYY signal to the brain to attenuate food intake, anxiety and
      depression-related behaviour. These findings underscore the important role of the
      NPY-Y receptor system at several levels of the gut-brain axis in which NPY, PYY
      and PP operate both as neural and endocrine messengers.

PMID- 22980003
TI  - Comparison of sample preparation methods for the recovery of foodborne pathogens
      from fresh produce.
AB  - Sample preparation methods (pummeling, pulsifying, sonication, and shaking by
      hand) were compared for achieving maximum recovery of foodborne pathogens from
      iceberg lettuce, perilla leaves, cucumber, green pepper, and cherry tomato.
      Antimicrobial and dehydration effects also were examined  to investigate causes
      of poor recovery of pathogens. Each produce type was inoculated with Escherichia
      coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes, Staphylococcus
      aureus, and Bacillus cereus at 6.0 log CFU/cm(2), and samples were prepared 
      using the four methods. Bacterial populations recovered from the five types of
      produce were significantly different (P < 0.05) according to sample preparation
      methods and produce type. The bacterial populations recovered from pummeled and
      pulsified samples were higher (P <  0.05) than those recovered from sonicated and
      hand-shaken samples, except for cherry tomato. The number of bacteria recovered
      from produce was reduced (P < 0.05) from that of the inoculum by 0.16 to 2.69 log
      CFU/cm(2). Although extracts of iceberg lettuce, perilla leaves,  cucumber, and
      green pepper had no antimicrobial activity, the populations of E. coli O157:H7,
      Salmonella Typhimurium, B. cereus, and L. monocytogenes in cherry tomato extract
      were slightly reduced after these treatments (P < 0.05). The pathogen populations
      on perilla leaves and cherry tomatoes decreased by >2 log CFU/cm(2) after
      exposure to 40% relative humidity for 1 h. No reduction was observed when the
      five pathogens were exposed to 90% relative humidity. These data suggest that
      pummeling and pulsifying are optimal sample preparation  methods for detection of
      microorganisms. Acidic produce such as cherry tomato should be treated with a
      method that does not cause sample breakdown so that acid stress on the bacteria
      can be minimized. Dehydration stress also affects recovery of pathogens from
      produce.

PMID- 22980004
TI  - Survival and growth of Salmonella enterica serovar enteritidis in membrane
      processed liquid egg white with pH, temperature, and storage conditions as
      controlling factors.
AB  - Processing temperature and pH are known to influence the lethality and cell
      injury in many microbial interventions. A study was undertaken to determine the
      effects of variations in solution pH and process temperature on the removal and
      growth of Salmonella enterica serovar Enteritidis  in liquid egg white (LEW) by
      microfiltration (MF) membrane process. The effects of various storage conditions
      on the growth of Salmonella in membrane-separated LEW were evaluated. Pretreated
      and pH-adjusted (pH 6 to pH 9) LEW was inoculated with a five-strain composite of
      S. enterica  serovar Enteritidis at ca. 7 log CFU/ml, microfiltered at 25 or 40
      degrees C, and stored at 4 or 10 degrees C. Temperature had a greater influence
      on Salmonella reduction than did pH. The maximum reduction of Salmonella and
      background microflora in LEW by MF was observed at 40 degrees C  and pH 8 and 9.
      However, the influence of temperature on permeate flow was less than that of pH.
      The mean permeate flow increased by 180% at 25 degrees C as the pH decreased from
      9 to 6, while flow increased merely by 18% at pH 6 as temperature increased from
      25 to 40 degrees C. Salmonella  populations in processed LEW at 4 degrees C
      storage remained quite stable (0.01 to 0.55 log CFU/ml), irrespective of MF
      experimental conditions. At 10 degrees C the population was greater, but no major
      outgrowth was observed. Findings from this study would be advantageous to liquid
      egg processing industries.

PMID- 22980005
TI  - Growth kinetics of listeria isolated from salmon and salmon processing
      environment: single strains versus cocktails.
AB  - The growth dynamics of Listeria monocytogenes strains isolated from salmon or a
      salmon processing environment and two reference Listeria innocua strains were
      investigated at refrigerated and close-to-optimal growth temperatures. Estimates
      for the growth rates and the lag-phase  duration at 4, 8, 12, and 30 degrees C
      were obtained for optical density measurements by using different growth
      parameter estimation methods, i.e., the serial dilution (SD) method and the
      relative rate to detection (RRD) method. Both single L. innocua and L.
      monocytogenes strains  and mixtures of L. monocytogenes strains (cocktails) were
      studied. Both methods show an increase in maximum growth rate (MU(max)) of
      Listeria with increasing temperatures. Generally, single-strain growth rate
      estimates were quite similar for both species, although  L. monocytogenes showed
      slightly higher MU(max) estimates at 4 degrees C. The SD method gave the highest
      estimates for the growth rate, i.e., the estimates from the RRD method were 10 to
      20% lower. This should lead to caution when using the latter method for Listeria,
      particularly at lower temperatures. Overall, the SD method is preferred as this
      method yields MU(max) estimates close to the biological value and provides
      estimates for the duration of lag time (lambda). For discrimination between
      different strains, lambda appeared to be a more  suitable parameter than MU(max).
      This effect was most prominent for L. innocua. Significant differences were
      observed between MU(max) and/or lambda of L. monocytogenes cocktails and single
      strains at all temperatures investigated. At 4 degrees C, the average  growth
      rate of cocktails was higher than that of single strains. At 8 and 30 degrees C,
      this trend was reversed. The average lambda of single strains were more than
      twice as long as those of cocktails at 4 degrees C. At 8 and 30 degrees C, the
      lambda of cocktails were significantly slower than those  of single strains, but
      the variation was considerably less and the differences were less pronounced.

PMID- 22980006
TI  - Thermal inactivation kinetics of Bacillus coagulans spores in tomato juice.
AB  - The thermal characteristics of the spores and vegetative cells of three strains
      of Bacillus coagulans (ATCC 8038, ATCC 7050, and 185A) in tomato juice were
      evaluated. B. coagulans ATCC 8038 was chosen as the target microorganism for
      thermal processing of tomato products  due to its spores having the highest
      thermal resistance among the three strains. The thermal inactivation kinetics of
      B. coagulans ATCC 8038 spores in tomato juice between 95 and 115 degrees C were
      determined independently in two different laboratories using two different
      heating setups.  The results obtained from both laboratories were in general
      agreement, with z-values (z-value is defined as the change in temperature
      required for a 10-fold reduction of the D-value, which is defined as the time
      required at a certain temperature for a 1-log reduction of  the target
      microorganisms) of 8.3 and 8.7 degrees C, respectively. The z-value of B.
      coagulans 185A spores in tomato juice (pH 4.3) was found to be 10.2 degrees C.
      The influence of environmental factors, including cold storage time, pH, and
      preconditioning, upon the thermal resistance  of these bacterial spores is
      discussed. The results obtained showed that a storage temperature of 4 degrees C
      was appropriate for maintaining the viability and thermal resistance of B.
      coagulans ATCC 8038 spores. Acidifying the pH of tomato juice decreased the
      thermal resistance of these  spores. A 1-h exposure at room temperature was
      considered optimal for preconditioning B. coagulans ATCC 8038 spores in tomato
      juice.

PMID- 22980007
TI  - Immunomagnetic capture of Bacillus anthracis spores from food.
AB  - Food is a vulnerable target for potential bioterrorist attacks; therefore, a
      critical mitigation strategy is needed for the rapid concentration and detection
      of biothreat agents from food matrices. Magnetic beads offer a unique advantage
      in that they have a large surface area for efficient  capture of bacteria. We
      have demonstrated the efficient capture and concentration of Bacillus anthracis
      (Sterne) spores using immunomagnetic beads for a potential food application.
      Magnetic beads from three different sources, with varying sizes and surface
      chemistries, were functionalized  with monoclonal antibodies and polyclonal
      antibodies from commercial sources and used to capture and concentrate anthrax
      spores from spiked food matrices, including milk, apple juice, bagged salad,
      processed meat, and bottled water. The results indicated that the Pathatrix beads
      were more  effective in the binding and capture of anthrax spores than the other
      two bead types investigated. Furthermore, it was observed that the use of
      polyclonal antibodies resulted in a more efficient recovery of anthrax spores
      than the use of monoclonal antibodies. Three different magnetic capture  methods,
      inversion, the Pathatrix Auto system, and the new i CropTheBug system, were
      investigated. The i CropTheBug system yielded a much higher recovery of spores
      than the Pathatrix Auto system. Spore recoveries ranged from 80 to 100% for the i
      CropTheBug system when  using pure spore preparations, whereas the Pathatrix Auto
      system had recoveries from 20 to 30%. Spore capture from food samples inoculated
      at a level of 1 CFU/ml resulted in 80 to 100% capture for milk, bottled water,
      and juice samples and 60 to 80% for processed meat and bagged salad when  using
      the i CropTheBug system. This efficient capture of anthrax spores at very low
      concentrations without enrichment has the potential to enhance the sensitivity of
      downstream detection technologies and will be a useful method in a foodborne
      bioterrorism response.

PMID- 22980008
TI  - Quantitative approach of risk management strategies for hepatitis a virus
      contaminated oyster production areas.
AB  - It is not yet known whether using the new molecular tools to monitor hepatitis A
      virus (HAV) in shellfish production areas could be useful for improving food
      safety. HAV contamination can be acute in coastal areas, such as Brittany,
      France, where outbreaks of hepatitis A have already  occurred and have been
      linked to the consumption of raw shellfish. A quantitative probabilistic approach
      was carried out to estimate the mean annual risk of hepatitis A in an adult
      population of raw oyster consumers. Two hypothetical scenarios of contamination
      were considered, the first for  a rare and brief event and the second for regular
      and prolonged episodes of contamination. Fourteen monitoring and management
      strategies were simulated. Their effects were assessed by the relative risk
      reduction in mean annual risk. The duration of closure after abnormal detection
      in the shellfish  area was also considered. Among the strategies tested, results
      show that monthly molecular reverse transcription PCR monitoring of HAV is more
      useful than bacterial surveys. In terms of management measures, early closure of
      the shellfish area without waiting for confirmatory analysis was shown  to be the
      most efficient strategy. When contamination is very short-lived and homogeneous
      in the shellfish production area, waiting for three negative results before
      reopening the area for harvest is time wasting. When contamination is not well
      identified or if contamination is heterogeneous,  it can be harmful not to wait
      for three negative results. In addition, any preventive measures, such as
      improving sewage treatment or producing shellfish in safer areas, that can reduce
      contamination by at least 2 log units are more efficient and less costly. Finally
      we show that controlling  and managing transferred shellfish are useful and can
      play an important role in preventing cases. Qualitative results from HAV
      monitoring can advantageously supplement other measures that improve the safety
      of shellfish products in exposed areas.

PMID- 22980009
TI  - Acaricidal activities of materials derived from Pyrus ussuriensis fruits against
      stored food mites.
AB  - The acaricidal activities of materials derived from Pyrus ussuriensis fruits were
      evaluated against Tyrophagus putrescentiae and compared with that of commercial
      acaricide (benzyl benzoate). On the basis of the 50 % lethal dose (LD(50))
      values, the ethyl acetate fraction of the fractions obtained from an aqueous
      extract of P. ussuriensis fruits had the highest acaricidal activity (16.32
      MUg/cm(2)) against T. putrescentiae. The acaricidal constituent of P. ussuriensis
      fruits was isolated by chromatographic techniques and identified as 1,4
      benzoquinone. On the basis of the LD(50) values, 1,4-benzoquinone (1.98
      MUg/cm(2)) was 5.9 times more toxic than benzyl benzoate (11.69 MUg/cm(2)),
      followed by 2-isopropyl-5-methyl-1,4-benzoquinone (3.29 MUg/cm(2)), and 2,3
      dimethoxy-5-methyl-1,4-benzoquinone (5.03 MUg/cm(2)) against T. putrescentiae in
      the fumigant bioassay. In a filter paper bioassay, the acaricidal activity of 1,4
      benzoquinone (0.07 MUg/cm(2)) was 120.1 times more effective than that of benzyl
      benzoate (8.41 MUg/cm(2)), followed by 2-isopropyl-5-methyl-1,4-benzoquinone
      (0.11 MUg/cm(2)) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (0.30 MUg/cm(2))
      against T. putrescentiae. These results demonstrate that P. ussuriensis fruit
      derived material and its derivatives have potential as new preventive agents for
      the control of stored food mites.

PMID- 22980010
TI  - Foodborne pathogens in in-line milk filters and associated on-farm risk factors
      in dairy farms authorized to produce and sell raw milk in northern Italy.
AB  - All dairy farms authorized to produce and sell raw milk in a province of Northern
      Italy were investigated to determine the presence of Campylobacter spp.,
      verocytotoxin-producing Escherichia coli (VTEC), Listeria monocytogenes, and
      Salmonella spp. in in-line  milk filters and to assess their association with
      suspected risk factors on farms. A logistic regression model was used to analyze
      data collected describing the characteristics and management practices of 27
      farms and the microbiological status of 378 in-line milk filters by both culture
      based  and molecular methods. Thermotolerant Campylobacter, VTEC, and L.
      monocytogenes were detected in 24 (6.45%), 32 (8.4%), and 2 (0.5%) samples,
      respectively. No Salmonella spp. were detected. For risk analysis, data of L.
      monocytogenes and Salmonella spp. were  not included in the model because of the
      low prevalence or absence of these organisms. The univariate analysis disclosed
      that the presence of VTEC and/or Campylobacter spp. in milk filters was
      associated with lack of cleanliness of bedding, water trough, and feed trough;
      nonevaluation  of water hardness; lack of cleanliness of milk tank; and
      nonapplication of forestripping. After multivariate analysis, an association was
      observed with inadequate cleanliness of bedding and milk tank and the
      nonapplication of forestripping. PCR analysis of milk filters was a rapid and
      sensitive  method for the microbiological evaluation of herd contamination status
      and should be included among the registration requirements for the authorization
      to produce and sell raw milk. Specific control actions must be incorporated into
      the farmer's daily practices to ensure the low-risk production of raw milk.

PMID- 22980011
TI  - Validation of a rapid lateral flow test for the simultaneous determination of
      beta-lactam drugs and flunixin in raw milk.
AB  - beta-Lactam antibiotics are the most commonly used drugs on dairy farms. beta
      Lactam residues in milk are kept out of the human milk supply with good
      agricultural practices and mandatory truck screening performed by the dairy
      industry under Appendix N of the Pasteurized Milk Ordinance.  Flunixin, a
      nonsteroidal and anti-inflammatory drug, appears in dairy cattle tissue residues
      with a frequency similar to the occurrence of penicillin G. This creates concern
      that flunixin residues could be in milk and would go undetected under current
      milk screening programs. A single test  that combines mandatory beta-lactam
      screening with voluntary flunixin screening is an economical approach for
      monitoring and controlling for potential flunixin or 5-hydroxyflunixin, the
      primary flunixin metabolite marker in milk. The objective of this study was to
      validate a beta-lactam  and flunixin rapid lateral flow test (LFT) and compare
      the results obtained with a liquid chromatography-triple quadrupole tandem mass
      spectrometry (LC-MS/MS) method for the simultaneous determination of flunixin and
      5-hydroxyflunixin in raw milk with a limit of detection of , 1 ppb, equivalent 
      to 1 ng/ml. Using the LFT, three combined manufactured lots of test strips
      detected penicillin G at 2.0 ppb, ampicillin at 6.8 ppb, amoxicillin at 5.9 ppb,
      cephapirin at 13.4 ppb, ceftiofur (total metabolites) at 63 ppb, and 5
      hydroxyflunixin at 1.9 ppb at least 90% of the time with 95% confidence.  The LFT
      also detected incurred flunixin milk samples that were analyzed with the LC-MS/MS
      and diluted to tolerance in raw milk. The detection levels for the LFT are lower
      than the U.S. safe levels or tolerances and qualify the test to be used in
      compliance with U.S. milk screening programs.

PMID- 22980012
TI  - Ranking the disease burden of 14 pathogens in food sources in the United States
      using attribution data from outbreak investigations and expert elicitation.
AB  - Understanding the relative public health impact of major microbiological hazards
      across the food supply is critical for a risk-based national food safety system.
      This study was conducted to estimate the U.S. health burden of 14 major pathogens
      in 12 broad categories of food and to then  rank the resulting 168 pathogen-food
      combinations. These pathogens examined were Campylobacter, Clostridium
      perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus,
      Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The
      health burden  associated with each pathogen was measured using new estimates of
      the cost of illness and loss of quality-adjusted life years (QALYs) from acute
      and chronic illness and mortality. A new method for attributing illness to foods
      was developed that relies on both outbreak data and expert elicitation.  This
      method assumes that empirical data are generally preferable to expert judgment;
      thus, outbreak data were used for attribution except where evidence suggests that
      these data are considered not representative of food attribution. Based on
      evaluation of outbreak data, expert elicitation,  and published scientific
      literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma,
      Cryptosporidium, and Yersinia were determined not representative; therefore,
      expert-based attribution were included for these four pathogens. Sensitivity
      analyses were conducted  to assess the effect of attribution data assumptions on
      rankings. Disease burden was concentrated among a relatively small number of
      pathogen-food combinations. The top 10 pairs were responsible for losses of over
      $8 billion and 36,000 QALYs, or more than 50 % of the total across all  pairs.
      Across all 14 pathogens, poultry, pork, produce, and complex foods were
      responsible for nearly 60 % of the total cost of illness and loss of QALYs.

PMID- 22980013
TI  - Annual cost of illness and quality-adjusted life year losses in the United States
      due to 14 foodborne pathogens.
AB  - In this article we estimate the annual cost of illness and quality-adjusted life
      year (QALY) loss in the United States caused by 14 of the 31 major foodborne
      pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011),
      based on their incidence estimates  of foodborne illness in the United States.
      These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of
      deaths due to identifiable pathogens estimated by Scallan et al. We estimate that
      these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to  $33.0
      billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to
      145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens:
      nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp.
      ($1.7 billion;  13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400
      QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion;
      5,000 QALYs). A companion article attributes losses estimated in this study to
      the consumption of specific categories  of foods. To arrive at these estimates,
      for each pathogen we create disease outcome trees that characterize the symptoms,
      severities, durations, outcomes, and likelihoods of health states associated with
      that pathogen. We then estimate the cost of illness (medical costs, productivity
      loss,  and valuation of premature mortality) for each pathogen. We also estimate
      QALY loss for each health state associated with a given pathogen, using the
      EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of
      illness, and EuroQol 5D scoring are described in greater detail  in a second
      companion article.

PMID- 22980014
TI  - Hand hygiene regimens for the reduction of risk in food service environments.
AB  - Pathogenic strains of Escherichia coli and human norovirus are the main etiologic
      agents of foodborne illness resulting from inadequate hand hygiene practices by
      food service workers. This study was conducted to evaluate the antibacterial and
      antiviral efficacy of various hand  hygiene product regimens under different soil
      conditions representative of those in food service settings and assess the impact
      of product formulation on this efficacy. On hands contaminated with chicken broth
      containing E. coli, representing a moderate soil load, a regimen combining  an
      antimicrobial hand washing product with a 70% ethanol advanced formula (EtOH AF)
      gel achieved a 5.22-log reduction, whereas a nonantimicrobial hand washing
      product alone achieved a 3.10log reduction. When hands were heavily soiled from
      handling ground beef containing E. coli, a wash-sanitize  regimen with a 0.5%
      chloroxylenol antimicrobial hand washing product and the 70% EtOH AF gel achieved
      a 4.60-log reduction, whereas a wash-sanitize regimen with a 62% EtOH foam
      achieved a 4.11-log reduction. Sanitizing with the 70% EtOH AF gel alone was more
      effective than hand washing with  a nonantimicrobial product for reducing murine
      norovirus (MNV), a surrogate for human norovirus, with 2.60- and 1.79-log
      reductions, respectively. When combined with hand washing, the 70% EtOH AF gel
      produced a 3.19-log reduction against MNV. A regimen using the SaniTwice protocol
      with the  70% EtOH AF gel produced a 4.04-log reduction against MNV. These data
      suggest that although the process of hand washing helped to remove pathogens from
      the hands, use of a wash-sanitize regimen was even more effective for reducing
      organisms. Use of a high-efficacy sanitizer as part of a wash-sanitize  regimen
      further increased the efficacy of the regimen. The use of a well-formulated
      alcohol-based hand rub as part of a wash-sanitize regimen should be considered as
      a means to reduce risk of infection transmission in food service facilities.

PMID- 22980015
TI  - Health professionals' knowledge and understanding about Listeria monocytogenes
      indicates a need for improved professional training.
AB  - Listeria monocytogenes causes listeriosis, an uncommon but potentially fatal
      disease in immunocompromised persons, with a public health burden of
      approximately $2 billion annually. Those consumers most at risk are the highly
      susceptible populations otherwise known as the  immunocompromised. Health
      professionals have a considerable amount of interaction with the
      immunocompromised and are therefore a valuable resource for providing appropriate
      safe food handling information. To determine how knowledgeable health
      professionals are about Listeria monocytogenes,  a nationwide Web-based survey
      was distributed targeting registered nurses (RNs) and registered dietitians (RDs)
      who work with highly susceptible populations. Responses were received from 499
      health professionals. Knowledge and understanding of Listeria monocytogenes was
      assessed descriptively.  Parametric and nonparametric analyses were used to
      detect differences between RNs and RDs. The major finding is that there are gaps
      in knowledge and a self-declared lack of understanding by both groups, but
      especially RNs, about Listeria monocytogenes. RDs were more likely than RNs  to
      provide information about specific foods and food storage behaviors to prevent a
      Listeria infection. Notably, neither group of health professionals consistently
      provided Listeria prevention messages to their immunocompromised patients.
      Pathogens will continue to emerge as  food production, climate, water, and waste
      management systems change. Health professionals, represented by RNs and RDs, need
      resources and training to ensure that they are providing the most progressive
      information about various harmful pathogens; in this instance, Listeria
      monocytogenes.

PMID- 22980016
TI  - Escherichia coli contamination of fish raised in integrated pig-fish aquaculture
      systems in Vietnam.
AB  - Integrated livestock-fish aquaculture utilizes animal excreta and urine as pond
      fertilizers to enhance growth of plankton and other microorganisms eaten by the
      fish. In Vietnam, pigs are commonly integrated with fish and horticulture in
      household-based VAC systems (vuon = garden;  ao = pond; chuong = pigsty), but the
      level of fecal contamination in the fish produced is unknown. This study was
      carried out to assess the level Escherichia coli contamination of fish meat and
      gut contents of grass carp (Ctenopharyngodon idellus), silver carp
      (Hypophthalmichthys  molitrix), and rohu (Labeo rohita) cultured in randomly
      selected five VAC ponds (with pig manure) and five non-VAC ponds (without pig
      manure) at sites in periurban Hanoi, Vietnam. Fish muscle tissue samples
      contained E. coli at <10 or 320 or 820 CFU/g, regardless of the  culture system
      from which they originated. In contrast, the intestinal contents of fish raised
      in manure-fed ponds contained E. coli at 4.75, 5.25, and 5.07 log CFU/g for
      silver carp, grass carp, and rohu, respectively, about 100 times higher than the
      contamination of fish from the  control ponds. The results indicate that muscle
      tissue of fish raised in VAC systems has a low level of fecal contamination
      despite high levels of E. coli in their gut. Thus, a critical point to control
      food safety of such fish is the prevention of fecal cross-contamination during
      degutting  and cleaning of the fish at markets and in the home.

PMID- 22980017
TI  - Prevalence of Salmonella and Vibrio spp. in seafood products sold in Singapore.
AB  - Foodborne hazards in seafood have only recently received increased attention in
      Singapore since the illness outbreak in 2009 that was associated with consumption
      of Indian rojak (a traditional salad of fruits, vegetables, and seafood). The
      microbiological quality of seafood must be  evaluated for assurance of food
      safety. The aim of this study was to evaluate the microbiological quality and to
      determine the prevalence of Salmonella and Vibrio spp. in seafood sold in
      Singapore. A total of 116 samples (41 prawn, 44 shellfish, and 31 fishball
      samples) were  collected from major supermarkets and wet markets in Singapore.
      The mesophilic and psychrotrophic bacterial counts for prawn, shellfish, and
      fishballs were 2 to 7 log CFU/g. One Salmonella Lexington strain was isolated
      from a thawed-frozen shellfish product and two Vibrio parahaemolyticus  strains
      were isolated from commercial fishball and shrimp meat products. Thus, seafood
      sold in Singapore has the potential to be contaminated with Vibrio spp. and
      Salmonella, and proper handling at food service establishments is required to
      ensure food safety. Effective control  measures also are needed to prevent cross
      contamination during postharvest seafood processing.

PMID- 22980018
TI  - Using nested PCR to detect the hlyA gene of Listeria monocytogenes in Minas
      Frescal cow's milk cheese.
AB  - To evaluate a nested PCR protocol for Listeria monocytogenes detection, Minas
      Frescal cow's milk cheeses were produced, artificially inoculated with this
      pathogen at concentrations ranging from 1 to 1,000 CFU/g, and stored at 4 degrees
      C for 10 days. The International Organization  for Standardization (ISO)
      standardized method 11290-1/A1 was used to detect L. monocytogenes in the
      inoculated samples, and DNA was extracted from aliquots (1, 5, and 10 ml) of 1:10
      dilution, followed by a nested PCR protocol for the hlyA gene. The ISO
      standardized reference  method and nested PCR both detected L. monocytogenes at
      all concentrations and during all storage periods; McNemar's test showed no
      significant difference (P > 0.05). The results indicated that the nested PCR
      protocol can be used as a screening test to detect L. monocytogenes  in Minas
      Frescal cheese, allowing earlier detection of the pathogen that can later be
      confirmed by the ISO standardized reference method.

PMID- 22980019
TI  - Generation of airborne Listeria innocua from model floor drains.
AB  - Listeria monocytogenes can colonize floor drains in poultry processing and
      further processing facilities, remaining present even after cleaning and
      disinfection. Therefore, during wash down, workers exercise caution to avoid
      spraying hoses directly into drains in an effort to  prevent the escape and
      transfer of drain microflora to food contact surfaces. The objective of this
      study was to examine the extent to which an inadvertent water spray into a
      colonized floor drain can cause the spread of airborne Listeria. Listeria innocua
      was used to inoculate  a polyvinyl chloride model floor drain, resulting in
      approximately 10(8) cells per ml of phosphate-buffered saline and 10(4) attached
      cells per square centimeter of inner surface. Each model drain was subjected to a
      2-s spray of tap water at 68.9 kPa from a distance of 1  m. Drains were sprayed
      while filled and again after emptying. Airborne cells were collected by using
      sedimentation plates containing Listeria selective agar which were placed on the
      floor and walls of a contained room at incremental horizontal and vertical
      distances of 0.6, 1.2, 2.4,  or 4.0 m from the drain. Sedimentation plates were
      exposed for 10 min. A mechanical sampler was used to also collect air by
      impaction on the surface of Listeria selective agar to determine the number of
      cells per liter of air. The experiment was conducted in triplicate rooms for each
      of four replications. L. innocua was detected on sedimentation plates on the
      floor as far as 4.0 m from the drain and on walls as high as 2.4 m above the
      floor and 4 m from the drain. A 2-s spray with a water hose into a contaminated
      drain can cause airborne spread of Listeria,  resulting in the potential for
      cross-contamination of food contact surfaces, equipment, and exposed product.

PMID- 22980020
TI  - Reduction of Listeria monocytogenes biofilms on stainless steel and polystyrene
      surfaces by essential oils.
AB  - Plant-derived essential oils were tested for their ability to eliminate biofilms
      of Listeria monocytogenes on polystyrene and stainless steel surfaces. Various
      concentrations of essential oils were tested with different contact times on
      biofilms of various ages. Preliminarily  screening of nine essential oils and
      related phenolic compounds in a disk diffusion assay revealed that thyme oil,
      oregano oil, and carvacrol had the highest antimicrobial activity. Further
      screening of these three compounds against 21 L. monocytogenes strains
      representing all 13 serotypes  indicated some strain-specific variations in
      antimicrobial activity. For 1-day-old biofilms of mixed L. monocytogenes strains
      produced at 22 degrees C on polystyrene microtiter plates, only 0.1%
      concentrations of thyme oil, oregano oil, and carvacrol were needed to eliminate
      7 log CFU per  well. On the stainless steel coupons, a 0.5% concentration of
      these compounds was adequate to completely eliminate 4-day-old biofilms at 7 log
      CFU per coupon. Our findings indicate that these compounds are potential
      candidates for elimination of L. monocytogenes biofilms on stainless steel and
      polystyrene surfaces.

PMID- 22980021
TI  - Bacteriological survey of ready-to-eat lettuce, fresh-cut fruit, and sprouts
      collected from the Swiss market.
AB  - The consumption of ready-to-eat fresh vegetables has increased significantly in
      the recent decades. So far, no data are available on the bacteriological burden
      and the prevalence of foodborne pathogens in ready-to-eat lettuce, fresh-cut
      fruit, and sprouts on the Swiss market. This study  was based on investigations
      carried out during 2 months of the summer season in 2011. Samples of 142 salads,
      64 fresh-cut fruit, and 27 sprouts were included in this study. Escherichia coli,
      an indicator microorganism for fecal contamination, was only found in 5 lettuce
      samples, with  amounts ranging between 2 and 3 log CFU/g. No Salmonella spp. were
      detected from any of the 233 samples analyzed in this study, and a low occurrence
      was found for contamination with L. monocytogenes, Shiga toxin-producing E. coli,
      enteropathogenic E. coli,  and Cronobacter. From the results of the present
      study, we conclude that even in a country where the use of chlorine solutions to
      sanitize fruits and vegetables in the fresh-cut industry is not allowed, it is
      possible to produce ready-to-eat lettuce, fresh-cut fruit, and sprouts with  high
      microbiological standards. Strict maintenance of good practices of hygiene at
      preharvest, harvest, and postharvest levels is of central importance to ensure
      both public health protection and product quality.

PMID- 22980022
TI  - Improvement of mannitol-yolk-polymyxin B agar by supplementing with trimethoprim
      for quantitative detection of Bacillus cereus in foods.
AB  - Mannitol-yolk-polymyxin B agar (MYPA) was modified by supplementation with
      trimethoprim. The ability of the supplemented medium to select for and recover
      Bacillus cereus from pure cultures and food samples with high background
      microflora was compared with MYPA. For  evaluation of the modified MYPA (mMYPA)
      in food samples with high background microflora, B. cereus was experimentally
      spiked into red pepper powder, fermented soybean paste, vegetable salad, and
      radish sprouts, and then it was recovered on MYPA and mMYPA for comparison. In
      all food  samples, there was no difference in recoverability (P > 0.05) between
      mMYPA (red pepper powder, 3.34 +/- 0.24 log CFU/g; fermented soybean paste, 3.52
      +/- 0.47 log CFU/g; vegetable salad, 3.51 +/- 0.23 log CFU/g; radish sprouts,
      3.32 +/- 0.40 log CFU/g) and MYPA  (red pepper powder, 3.18 +/- 0.20 log CFU/g;
      fermented soybean paste, 3.33 +/- 0.43 log CFU/g; vegetable salad, 3.36 +/- 0.19
      log CFU/g; radish sprouts, 3.33 +/- 0.31 log CFU/g). However, mMYPA exhibited
      better selectivity than MYPA, because additional trimethoprim made  the
      differentiation of suspected colonies easier by inhibiting competing flora. The
      addition of trimethoprim to conventional media could be a useful option to
      improve selectivity in foods with high background microflora.

PMID- 22980023
TI  - Inhibition of toxigenesis of group II (nonproteolytic) Clostridium botulinum type
      B in meat products by using a reduced level of nitrite.
AB  - The effect of three different concentrations of sodium nitrite (0, 75, and 120
      mg/kg) on growth and toxigenesis of group II (nonproteolytic) Clostridium
      botulinum type B was studied in Finnish wiener-type sausage, bologna-type
      sausage, and cooked ham. A low level of inoculum  (2.0 log CFU/g) was used for
      wiener-type sausage and bologna-type sausage, and both low (2.0 log CFU/g) and
      high (4.0 log CFU/g) levels were used for cooked ham. The products were
      formulated and processed under simulated commercial conditions and stored at 8
      degrees C for 5 weeks. C. botulinum  counts were determined in five replicate
      samples of each nitrite concentration at 1, 3, and 5 weeks after thermal
      processing. All samples were positive for C. botulinum type B. The highest C.
      botulinum counts were detected in nitrite-free products. Toxigenesis was observed
      in  nitrite-free products during storage, but products containing either 75 or
      120 mg/kg nitrite remained nontoxic during the 5-week study period, suggesting
      that spores surviving the heat treatment were unable to germinate and develop
      into a toxic culture in the presence of nitrite. The results  suggest that the
      safety of processed meat products with respect to group II C. botulinum type B
      can be maintained even with a reduced concentration (75 mg/kg) of sodium nitrite.

PMID- 22980024
TI  - Effects of a variety of food extracts and juices on the specific binding ability
      of norovirus GII.4 P particles.
AB  - The effects of 13 food extracts and juices, including shellfish, fruits, and
      vegetables, on the binding ability of human norovirus (NoV) were examined, using
      P particles of human NoV GII.4 as a research surrogate. The enhancements
      (positive values) or reductions (negative values) of  NoV P particle detection
      (changes in optical density at 450 nm) in the presence of different food extracts
      and juices as compared with P particles diluted in phosphate-buffered saline were
      tested by saliva-binding, enzyme-linked immunosorbent assay in triplicate. In the
      presence of different  food extracts and juices at different concentrations, an
      increase or decrease of the receptor-binding ability of the NoV P particles was
      observed. Due to a higher specific binding and thus a higher accumulation of the
      viral particles, oysters may be contaminated with human NoV more often than 
      other shellfish species (mussel, hard clams, and razor clams). Cranberry and
      pomegranate juices were shown to reduce the specific binding ability of human NoV
      P particles. No such binding inhibition effects were observed for the other
      tested extracts of fresh produce (strawberry, blackberry,  blueberry, cherry
      tomato, spinach, romaine lettuce) or, notably, for raspberry, which has been
      associated with human NoV outbreaks.

PMID- 22980025
TI  - Development of a purification method for simultaneous determination of
      deoxynivalenol and its acetylated and glycosylated derivatives in corn grits and
      corn flour by liquid chromatography-tandem mass spectrometry.
AB  - We developed a purification method based on liquid chromatography-tandem mass
      spectrometry for the identification of deoxynivalenol (DON), its acetylated
      derivatives (3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol), and a
      glycosylated derivative (deoxynivalenol-3-glucoside  [D3G]) in corn-based
      products. The analytes were extracted from samples with acetonitrile-water
      (85:15, vol/vol) and then purified with multifunctional columns. Evaluation of
      five kinds of multifunctional columns revealed that DON and its acetylated
      derivatives were recovered well (96 to 120%)  by all columns, but D3G was
      recovered adequately (93.5%) by only one column, InertSep VRA-3. Samples of corn
      grits and corn flour were analyzed using the purification method with InertSep
      VRA-3. DON, D3G, and 15-acetyl-deoxynivalenol were the major contaminants in the
      samples harvested in  2009, but only DON was detected in the samples harvested in
      2010. These results suggest that the purification method using InertSep VRA-3 is
      effective for identification of DON and its derivatives in corn-based products.

PMID- 22980026
TI  - Adaptive acid tolerance response of Listeria monocytogenes strains under
      planktonic and immobilized growth conditions.
AB  - The acid resistance of Listeria monocytogenes was evaluated: (i) after short
      (shock) or long-term (adaptation during growth) exposure to reduced (5.5) or
      neutral (7.2) pH in a liquid (broth) medium or on a solid surface (agar), and
      (ii) after growth on the surface of ham and turkey slices or in homogenates of
      these products. Three L. monocytogenes strains (serotypes 1/2a, 1/2b and 4b) were
      individually inoculated at: (i) 10(4)-10(5)CFU/ml in tryptic soy broth with 0.6%
      yeast extract (TSBYE) or on tryptic soy agar with 0.6% yeast extract (TSAYE) at
      pH 7.2 with 1% (+G) or without (-G) glucose of or TSBYE and TSAYE with 0.25%
      glucose at pH 5.5 (lactic acid) and incubated at 20 degrees C, and (ii) 10(2)
      10(3)CFU/cm(2) on ham and turkey slices (pH 6.39-6.42; formulated with potassium
      lactate and sodium diacetate) or in their homogenates (1:4 and 1:9; representing
      viscous [slurry] and liquid residues [purge], respectively), and stored at 10
      degrees C. The acid resistance of each strain was assessed in TSBYE of pH 3.5
      (lactic acid) for strains growing in broth or on agar surfaces, and in TSBYE of
      pH 1.5 (HCl) for strains growing on ham and turkey slices or in their
      homogenates. Habituation at pH 5.5 for 3 or 24h at 20 degrees C increased acid
      (pH 3.5) resistance of all strains compared to the control (pH 7.2). Cells grown
      on the surface of TSAYE-G (pH 7.2 or 5.5) showed higher resistance than cells
      grown in broth (TSBYE-G), whereas the opposite was observed for cells grown on
      TSAYE + G or in TSBYE + G. Growth of L. monocytogenes on meat product slices was
      markedly slower than in homogenates. Pathogen reductions following exposure to pH
      1.5, after 10 and 27days of storage were strain-dependent and in the ranges of
      0.5-2.5, 1.3-4.5 and 4.0-7.6 log units for cells grown on product slices in 1:4
      and 1:9 homogenates, respectively. The results suggest that L. monocytogenes
      cells growing on food surfaces or in viscous matrices may show higher resistance
      to lethal acid conditions than cells growing in liquid substrates.

PMID- 22980027
TI  - Familial ALS with FUS P525L mutation: two Japanese sisters with multiple systems
      involvement.
AB  - We evaluated the clinicopathological features of familial amyotrophic lateral
      sclerosis (ALS) with the fused in sarcoma (FUS) P525L mutation. Two sisters and
      their mother had a similar clinical course, which was characterized by the
      development of limb weakness at a young age with rapid disease progression. An
      elder sister, patient 1, progressed into a totally locked-in state requiring
      mechanical ventilation and died 26 years after the onset of the disease. In
      contrast, the younger sister, patient 2, died in the early stages of the disease.
      The patients had neuropathological findings that indicated a very active
      degeneration of motor neurons and multiple system degeneration, which led to
      marked brain and spinal cord atrophy in the long term clinical outcome. The
      multiple system degeneration included the frontal lobe, the basal ganglia and
      substantia nigra, cerebellum and related area. Compared with previously reported
      ALS cases, the severe degeneration of the frontal lobe and the striatum were the
      characteristic features in the patient 1 in this case study. The degeneration
      spread over multiple systems might be caused not only by the appearance of the
      FUS immunoreactive neuronal cytoplasmic inclusions but also by the degeneration
      of neuronal connections from the primary motor cortex and related areas.

PMID- 22980028
TI  - Understanding wealth-based inequalities in child health in India: a decomposition
      approach.
AB  - India experienced tremendous economic growth since the mid-1980s but this growth
      was paralleled by sharp rises in economic inequality. Urban areas experienced
      greater economic growth as well as greater increases in economic inequality than
      rural areas. During the same period, child health improved on average but
      socioeconomic differentials in child health persisted. This paper attempts to
      explain wealth-based inequalities in child mortality and malnutrition using a
      regression-based decomposition approach. Data for the analysis come from the
      1992/93, 1998/99, and 2005/06 Indian National Family Health Surveys. Inequalities
      in child health are measured using the concentration index. The concentration
      index for each outcome is then decomposed into the contributions of wealth-based
      inequality in the observed determinants of child health. Results indicate that
      mortality inequality declined in urban areas but remained unchanged or increased
      in rural areas. Malnutrition inequality increased dramatically both in urban and
      rural areas. The two largest individual/household-level sources of disparities in
      child health are (i) inequality in the distribution of wealth itself, and (ii)
      inequality in maternal education. The contributions of observed determinants (i)
      to neonatal mortality inequality remained unchanged, (ii) to child mortality
      inequality increased, and (ii) to malnutrition inequality increased. It is
      possible that the increases in child health inequality reflect urban biases in
      economic growth, and the mixed performance of public programs that could have
      otherwise offset the impacts of unequal growth.

PMID- 22980029
TI  - Differences in the biokinetics of inhaled nano- versus micrometer-sized
      particles.
AB  - Researchers need to study the biokinetics of inhaled biopersistent nano- and
      micrometer-sized particles (NPs and MUPs) to assess their toxicity and to develop
      an understanding of their potential risks. When particles are inhaled, they do
      not necessarily remain at their sites of deposition in the respiratory tract.
      Instead they can undergo numerous transport processes within the various tissues
      of the lungs, including clearance from the lungs. In this context, we would like
      to understand how the biokinetic studies performed in animals can be extrapolated
      to humans. Interestingly, the particle retention is much shorter in rodent lungs
      and declines much faster than it does in human, simian, and canine lungs. The
      predominant long-term clearance pathway for both NPs and MUPs in humans and other
      animal species is macrophage-mediated particle transport from the peripheral
      lungs toward ciliated airways and the larynx. However, the transport rate is 10
      times higher in rodents than in other species. In addition to particle clearance
      out of the lung, we also observe particle redistribution from the epithelium
      toward and within the interstitium and lymph nodes of the lung and particle
      translocation to blood circulation leading to subsequent accumulation in
      secondary organs. While MUPs have limited access to interstitial spaces in the
      rodent lungs, NPs rapidly relocate in the epithelium and the underlying
      interstitium. By contrast, indirect evidence shows that both NPs and MUPs are
      relocated into the epithelium and interstitial spaces of the human, simian, and
      canine lungs. Only NPs translocate into the circulatory system and subsequently
      accumulate in the secondary organs and tissues of the body. Translocated NP
      fractions are rather low, but they depend strongly on the physicochemical
      properties of the NP and their surface properties. Growing evidence indicates
      that the binding and conjugation of proteins to NPs play an essential role in
      translocation across cellular membranes and organ barriers. In summary, particle
      biokinetics result from a multitude of highly dynamic processes, which depend not
      only on physicochemical properties of the particles but also on a multitude of
      cellular and molecular responses and interactions. Given the rather small
      accumulation in secondary organs after acute inhalation exposures, it appears
      likely that adverse effects caused by NPs accumulated in secondary organs may
      only occur after chronic exposure over extended time periods. Therefore adverse
      health effects in secondary organs such as the cardiovascular system that are
      associated with chronic exposure of ambient urban air pollution are less likely
      to result from particle translocation. Instead, chronic particle inhalation could
      trigger or modulate the autonomous nervous system or the release of soluble
      mediators into circulation leading to adverse health effects.

PMID- 22980030
TI  - Heritability versus the role of the environment in autoimmunity.
AB  - The higher concordant occurrence of autoimmune diseases in monozygotic twins
      compared to dizygotic or sibling pairs supports the role for genetic
      susceptibility. For most conditions, however, concordance rates are considerably
      below 100% and lead to the estimate of the weight of genetics coined
      "heritability". In the group of autoimmune diseases heritability ranges between
      0.008 and 1 with median values of approximately 0.60. A complementary term coined
      "environmentability" represents the environmental influence on individual
      phenotype, and can include dietary habits, chemicals, or hygienic conditions.
      Genome-wide association data in complex diseases confirmed a role for the
      environment in disease etiology as significantly associated polymorphisms were
      found only in subgroups of patients and controls. Environmental links to
      autoimmunity range from anecdotal associations or case series to largely
      investigated experimental and epidemiological studies. A bibliographic analysis
      reveals that the number of publications dedicated to environmental factors in
      autoimmunity has grown on average by 7% every year since 1997. The National
      Institute of Environmental Health Sciences (NIEHS) convened an expert panel
      workshop to review the body of literature examining the role of the environment
      in the development of autoimmune disease and to identify conclusions,
      confidences, and critical knowledge gaps in this area. The results of the
      workshop discussion are summarized in the articles found in this issue of the
      Journal of Autoimmunity.

PMID- 22980031
TI  - Recombinant IL-6 treatment protects mice from organ specific autoimmune disease
      by IL-6 classical signalling-dependent IL-1ra induction.
AB  - Cytokines are key regulators of physiological inflammatory responses, while
      aberrant cytokine expression contributes to pathogenesis of autoimmune diseases.
      We noted increased IL-6 levels in human and murine epidermolysis bullosa
      acquisita (EBA), a prototypic organ-specific autoimmune bullous dermatoses (AIBD)
      induced by autoantibodies to type VII collagen (COL7). In contrast to rheumatoid
      arthritis, blockade of IL-6 led to strikingly enhanced experimental EBA, while
      treatment with recombinant IL-6 was protective. This was due to classical IL-6
      signalling and independent of IL-6 trans-signalling, as treatment of mice with
      sgp130Fc had no impact on EBA manifestation. Induction of EBA in mice led to
      increased IL-1ra levels in skin and serum, while blockade of IL-6 completely
      inhibited IL-1ra expression induced by autoantibodies to COL7. In line, treatment
      of mice with EBA with recombinant IL-6 induced IL-1ra concentrations exceeding
      those of untreated animals with EBA, and IL-1ra (anakinra) administration
      significantly impaired experimental EBA induction. We here identified a novel
      anti-inflammatory pathway in an organ-specific autoimmune disease. Modulation of
      this IL-1ra pathway by classical IL-6 signalling demonstrates anti-inflammatory
      and protective activities of IL-6 in vivo.

PMID- 22980032
TI  - Liquid state 1H high field NMR in food analysis.

PMID- 22980033
TI  - Mixture and dissolution of laser polarized noble gases: spectroscopic and imaging
      applications.

PMID- 22980034
TI  - The mechanics behind cell polarity.
AB  - The generation of cell polarity is one of the most intriguing symmetry-breaking
      events in biology. It is involved in almost all physiological and developmental
      processes and, despite the differences between plant and animal cell structures,
      cell polarity is generated by a similar core mechanism that comprises the
      extracellular matrix (ECM), Rho GTPase, the cytoskeleton, and the membranes.
      Several recent articles show that mechanical factors also contribute to the
      establishment and robustness of cell polarity, and the different molecular actors
      of cell polarity are now viewed as integrators of both biochemical and mechanical
      signals. Although cell polarity remains a complex process, some level of
      functional convergence between plants and animals is revealed. Following
      comparative presentation of cell polarity in plants and animals, we will discuss
      the theoretical background behind the role of mechanics in polarity and the
      relevant experimental tests, focusing on ECM anchorage, cytoskeleton behavior,
      and membrane tension.

PMID- 22980035
TI  - The role of lipids in defining membrane protein interactions: insights from mass
      spectrometry.
AB  - Cellular membranes comprise hundreds of lipids in which protein complexes, such
      as ion channels, receptors, and scaffolding complexes, are embedded. These
      protein assemblies act as signalling and trafficking platforms for processes
      fundamental to life. Much effort in recent years has focused on identifying the
      protein components of these complexes after their extraction from the lipid
      membrane in detergent micelles. Spectacular advances have been made using X-ray
      crystallography, providing in some cases detailed information about the mechanism
      of pumping and channel gating. These structural studies are leading to a growing
      realisation that, to understand their function, it is not only the structures of
      the protein components that are important but also knowledge of the protein-lipid
      interactions. This review highlights recent insights gained from this knowledge,
      surveys methods being developed for probing these interactions, and focuses
      specifically on the potential of mass spectrometry in this growing area of
      research.

PMID- 22980036
TI  - Prognostic scoring systems in MDS.
AB  - Prognostic scoring systems in myelodysplastic syndromes are useful tools in order
      to get in idea on the expected course of the disease and offer patients a risk
      adapted treatment. Several good scores have been developed, the international
      prognostic scoring system (IPSS) being the gold standard for 15 years, now
      validated and refined. As more and more patients receive therapy and drugs are
      approved, the major goal for future projects must be the identification of
      predictive parameters and scoring systems in order to predict the response and
      outcome after specific treatments.

PMID- 22980040
TI  - Early determinants of chronic disease. Preface.

PMID- 22980038
TI  - Immune genes are associated with human glioblastoma pathology and patient
      survival.
AB  - BACKGROUND: Glioblastoma (GBM) is the most common and lethal primary brain tumor
      in adults. Several recent transcriptomic studies in GBM have identified different
      signatures involving immune genes associated with GBM pathology, overall survival
      (OS) or response to treatment. METHODS: In order to clarify the immune signatures
      found in GBM, we performed a co-expression network analysis that grouped 791
      immune-associated genes (IA genes) in large clusters using a combined dataset of
      161 GBM specimens from published databases. We next studied IA genes associated
      with patient survival using 3 different statistical methods. We then developed a
      6-IA gene risk predictor which stratified patients into two groups with
      statistically significantly different survivals. We validated this risk predictor
      on two other Affymetrix data series, on a local Agilent data series, and using RT
      Q-PCR on a local series of GBM patients treated by standard chemo-radiation
      therapy. RESULTS: The co-expression network analysis of the immune genes
      disclosed 6 powerful modules identifying innate immune system and natural killer
      cells, myeloid cells and cytokine signatures. Two of these modules were
      significantly enriched in genes associated with OS. We also found 108 IA genes
      linked to the immune system significantly associated with OS in GBM patients. The
      6-IA gene risk predictor successfully distinguished two groups of GBM patients
      with significantly different survival (OS low risk: 22.3 months versus high risk:
      7.3 months; p < 0.001). Patients with significantly different OS could even be
      identified among those with known good prognosis (methylated MGMT promoter
      bearing tumor) using Agilent (OS 25 versus 8.1 months; p < 0.01) and RT-PCR (OS
      21.8 versus 13.9 months; p < 0.05) technologies. Interestingly, the 6-IA gene
      risk could also distinguish proneural GBM subtypes. CONCLUSIONS: This study
      demonstrates the immune signatures found in previous GBM genomic analyses and
      suggests the involvement of immune cells in GBM biology. The robust 6-IA gene
      risk predictor should be helpful in establishing prognosis in GBM patients, in
      particular in those with a proneural GBM subtype, and even in the well-known good
      prognosis group of patients with methylated MGMT promoter-bearing tumors.

PMID- 22980041
TI  - Early determinants of type-2 diabetes.
AB  - The global prevalence of type-2 diabetes (T2D) has more than doubled in the last
      30 years and is predicted to continue to rise at an alarming rate. The associated
      health and financial burdens are considerable. The aetiology of common forms of
      T2D is multifactorial and involves a complex interplay between genetic,
      epigenetic and environmental factors. The influential role of the environment, in
      particular our diet and sedentary lifestyles, in diabetes risk is well
      established. Of major concern is the increasing prevalence of early onset T2D or
      pre-diabetic characteristics in children. In recent years, the role of the early
      life environment in programming diabetes risk has been the focus of numerous
      human and animal studies. Historical studies highlighted an association between
      low birthweight, a proxy for suboptimal in utero growth, and diabetes risk in
      adulthood. Over more recent years it has become apparent that a variety of
      expositions, including maternal obesity and/or maternal diabetes, can have a
      significant effect on offspring health outcomes. Further complicating matters,
      paternal and transgenerational transmission of T2D can occur thus mediating a
      perpetuating cycle of disease risk between generations. It is imperative for the
      underlying mechanisms to be elucidated so that interventions can be introduced.
      In doing so, it may be possible to prevent, delay or reverse a pre-programmed
      risk for T2D induced by pre- and/or postnatal environmental factors to improve
      health outcomes and curb premature metabolic decline. This review presents
      evidence for how the early life environment may programme T2D risk and suggests
      some mechanisms by which this may occur.

PMID- 22980042
TI  - Early determinants of cardiovascular disease.
AB  - According to the Developmental Origins of Health and Disease hypothesis
      intrauterine or postnatal adaptations to the environment causes morphologic,
      physiologic or metabolic changes that influence health later in life. These
      adaptations seem to be carried out through structural, functional and epigenetic
      modifications. Multiple animal models of cardiovascular programming have been
      developed, and a brief overview of well-known models and mechanisms is presented.
      However, developmental programming also offers a novel approach to prevent
      cardiovascular and related diseases through so-called Reprogramming:
      administration of appropriate or inhibition of deleterious perinatal factors in
      induced or genetic models ameliorated undesirable development that otherwise
      would inevitably have lead to more severe hypertension, cardiovascular and renal
      disease. A comprehensive overview of these studies suggests that, in analogy to
      what has been previously recognised in programming, many quite different
      reprogramming interventions all have similar protective effects. Whether this is
      due to common final epigenetic pathways remains to be shown.

PMID- 22980043
TI  - Early determinants of mental health.
AB  - Environmental adversities in pre- and early postnatal life may have life-long
      consequences. Based upon a series of epidemiological and clinical studies and
      natural experiments, this review describes how the early life environment may
      affect psychological functions and mental disorders later in life. We focus on
      studies that have examined the associations of small body size at birth and
      prematurity as proxies of prenatal environmental adversity. We also review
      literature on materno-fetal malnutrition, maternal prenatal glycyrrhizin in
      licorice consumption and hypertension-spectrum pregnancy disorders as factors
      that may compromise the fetal developmental milieu and hence provide insight into
      some of the mechanisms that may underlie prenatal programming. While effects of
      programming mostly take place during the first 1000 days after conception, we
      finally present evidence from prospective studies suggesting that programming can
      occur also during later critical periods of development or 'windows of
      plasticity'. The studies may bear relevance for future prevention and
      intervention programs targeting the potentially modifiable environmental factors
      that will aid at promoting mental well-being and health of an individual.

PMID- 22980044
TI  - Early determinants of the ageing trajectory.
AB  - Over the past 250 years, human life expectancy has increased dramatically and
      continues to do so in most countries worldwide. Genetic factors account for about
      one third of variation in life expectancy so that most inter-individual variation
      in lifespan is explained by stochastic and environmental factors. The ageing
      process is plastic and is driven by the accumulation of molecular damage causing
      the changes in cell and tissue function which characterise the ageing phenotype.
      Early life exposures mark the developing embryo, foetus and child with
      potentially profound implications for the individual's ageing trajectory.
      Maternal factors including age, smoking, socioeconomic status, infections,
      nutritional status and season of birth influence offspring life expectancy and
      the development of age-related diseases. Although the mechanistic processes
      responsible are poorly understood, many of these factors appear to affect foetal
      growth directly or via effects on placental development. Those born relatively
      small i.e. which did not achieve their genetic potential in utero, appear to be
      at greatest disadvantage especially if they become overweight or obese in
      childhood. Early life events and exposures which enhance ageing are likely to
      contribute to molecular damage and/or reduce the repair of such damage. Such
      molecular damage may produce immediate defects in cellular or tissue function
      that are retained into later life. In addition, there is growing evidence that
      early life exposures produce aberrant patterns of epigenetic marks that are
      sustained across the life-course and result in down-regulation of cell defence
      mechanisms.

PMID- 22980045
TI  - Maternal obesity, gestational weight gain and diet as determinants of offspring
      long term health.
AB  - This review addresses the increasingly prolific literature from studies in man
      and animals suggesting that maternal obesity, a diet rich in calories or excess
      gestational weight gain may, through perturbation of the intrauterine
      environment, lead to lifelong risk of obesity and related disorders in the child.
      In addressing maternal- child obesity relationships it remains a challenge to
      distinguish the influence of the intrauterine environment from the contribution
      of shared genetic traits, and to adequately adjust for postnatal determinants of
      childhood obesity. Studies in genetically identical rodents convincingly show
      that maternal obesity, as well as elements of a hypercalorific diet can
      permanently influence offspring risk of obesity, and are these are supported by
      studies in larger mammals. Importantly, dissection of the mechanism in animals
      has led to description of novel interactive pathways between maternal environment
      and fetus which are amenable to investigation in humans.

PMID- 22980046
TI  - Early postnatal life as a critical time window for determination of long-term
      metabolic health.
AB  - Epidemiological studies demonstrated a clear phenomenological association between
      low birth weight and increased cardiometabolic risk later in life, very similar
      to that in high birth weight subjects. Pre- and/or neonatal overfeeding appears
      to be an etiological clue. In animal studies, irrespective of birth weight
      neonatal over-nutrition leads to later overweight, impaired glucose tolerance and
      cardiometabolic alterations. Probably, perinatally acquired alterations of DNA
      methylation patterns of gene promoters of central nervous regulators of body
      weight and metabolism play a key role in mediating these relationships. In
      humans, the long-term impact of neonatal nutrition is conclusively demonstrated
      by studies on the consequences of breastfeeding vs. formula-feeding. Taken
      together, the quantity and quality of nutrition during neonatal life plays a
      critical role, beyond prenatal development, in the long-term programming of
      health and disease. This opens a variety of opportunities and challenges to
      primarily prevent chronic diseases, e.g. the metabolic syndrome.

PMID- 22980037
TI  - Shedding new light on neurodegenerative diseases through the mammalian target of
      rapamycin.
AB  - Neurodegenerative disorders affect a significant portion of the world's
      population leading to either disability or death for almost 30 million
      individuals worldwide. One novel therapeutic target that may offer promise for
      multiple disease entities that involve Alzheimer's disease, Parkinson's disease,
      epilepsy, trauma, stroke, and tumors of the nervous system is the mammalian
      target of rapamycin (mTOR). mTOR signaling is dependent upon the mTORC1 and
      mTORC2 complexes that are composed of mTOR and several regulatory proteins
      including the tuberous sclerosis complex (TSC1, hamartin/TSC2, tuberin). Through
      a number of integrated cell signaling pathways that involve those of mTORC1 and
      mTORC2 as well as more novel signaling tied to cytokines, Wnt, and forkhead, mTOR
      can foster stem cellular proliferation, tissue repair and longevity, and synaptic
      growth by modulating mechanisms that foster both apoptosis and autophagy. Yet,
      mTOR through its proliferative capacity may sometimes be detrimental to central
      nervous system recovery and even promote tumorigenesis. Further knowledge of mTOR
      and the critical pathways governed by this serine/threonine protein kinase can
      bring new light for neurodegeneration and other related diseases that currently
      require new and robust treatments.

PMID- 22980047
TI  - Early determinants of chronic disease in developing countries.
AB  - The prevalence of non-communicable diseases (NCDs) is rising in developing
      countries. The extent to which this is due to a nutritional mismatch in foetal
      and adult life is unknown however, studies in such countries show that the risk
      of chronic diseases is increased in low birthweight subjects who become obese
      adults. Immune dysfunction is also linked to low birthweight. Therefore, in
      countries where communicable diseases are prevalent, infection may be exacerbated
      by factors acting in utero. It is also possible that the foetal growth-retarding
      effects of maternal Human Immunodeficiency Virus (HIV) and malaria infection may
      contribute to an increased risk of NCDs later in life. Low birthweight and
      postnatal growth faltering followed by rapid weight gain define subjects who
      develop NCDs. Dietary interventions at specific time points in the life course
      may therefore be important for reducing disease risk.

PMID- 22980048
TI  - Epigenetic mechanisms linking early nutrition to long term health.
AB  - Traditionally it has been widely accepted that our genes together with adult
      lifestyle factors determine our risk of developing non-communicable diseases such
      as type 2 diabetes mellitus, cardiovascular disease and obesity in later life.
      However, there is now substantial evidence that the pre and early postnatal
      environment plays a key role in determining our susceptible to such diseases in
      later life. Moreover the mechanism by which the environment can alter long term
      disease risk may involve epigenetic processes. Epigenetic processes play a
      central role in regulating tissue specific gene expression and hence alterations
      in these processes can induce long-term changes in gene expression and metabolism
      which persist throughout the lifecourse. This review will focus on how
      nutritional cues in early life can alter the epigenome, producing different
      phenotypes and altered disease susceptibilities.

PMID- 22980049
TI  - Leptin as mediator of the effects of developmental programming.
AB  - Considerable epidemiological, experimental and clinical data have amassed showing
      that the risk of developing disease in later life is dependent upon early life
      conditions. In particular, altered maternal nutrition, including undernutrition
      and overnutrition, can lead to metabolic disorders in offspring characterised by
      obesity and leptin resistance. The adipokine leptin has received significant
      interest as a potential programming factor; alterations in the profile of leptin
      in early life are associated with altered susceptibility to obesity and metabolic
      disorders in adulthood. Maintenance of a critical leptin level during early
      development facilitates the normal maturation of tissues and signalling pathways
      involved in metabolic homeostasis. A period of relative hypo- or hyperleptinemia
      during this window of development will induce some of the metabolic adaptations
      which underlie developmental programming. However, it remains unclear whether
      leptin alone is a critical factor for the programming of obesity. At least in
      animal experimental studies, developmental programming is potentially reversible
      by manipulating the concentration of circulating leptin during a critical window
      of developmental plasticity and offers an exciting new approach for therapeutic
      intervention.

PMID- 22980050
TI  - Glucocorticoids as mediators of developmental programming effects.
AB  - Epidemiological evidence suggests that exposure to an adverse environment in
      early life is associated with an increased risk of cardio-metabolic and
      behavioral disorders in adulthood, a phenomenon termed 'early life programming'.
      One major hypothesis for early life programming is fetal glucocorticoid
      overexposure. In animal studies, prenatal glucocorticoid excess as a consequence
      of maternal stress or through exogenous administration to the mother or fetus is
      associated with programming effects on cardiovascular and metabolic systems and
      on the brain. These effects can be transmitted to subsequent generations. Studies
      in humans provide some evidence that prenatal glucocorticoid exposure may exert
      similar programming effects on glucose/insulin homeostasis, blood pressure and
      neurodevelopment. The mechanisms by which glucocorticoids mediate these effects
      are unclear but may include a role for epigenetic modifications. This review
      discusses the evidence for glucocorticoid programming in animal models and in
      humans.

PMID- 22980052
TI  - The epidemiology and pathophysiology of heart failure.
AB  - Heart failure (HF) remains a major growing public health problem in the United
      States. Despite extensive understanding of the mechanism at the molecular level
      and innovations in therapy, HF carries high morbidity and mortality rates, with
      frequent hospital admissions. In the Medicare population, HF is the leading cause
      for hospitalization, accounting for more than1 million admissions per year. The
      authors provide a review of the epidemiology and pathophysiology of HF.

PMID- 22980053
TI  - Pathophysiology of systolic and diastolic heart failure.
AB  - Systolic and diastolic heart failure are the 2 most common clinical subsets of
      chronic heart failure. Left ventricular "Starling" function is depressed in
      patients with systolic heart failure. In systolic heart failure, left ventricular
      mass is increased, which can be measured by transthoracic echocardiography.
      Cardiac magnetic resonance imaging is a more precise technique to measure left
      ventricular mass. Neurohormonal activation is a major pathophysiologic mechanism
      for ventricular remodeling and progression of heart failure in systolic heart
      failure.

PMID- 22980051
TI  - Developmental origins of diabetes: The role of oxidative stress.
AB  - The 'thrifty phenotype' hypothesis proposes that the fetus adapts to an adverse
      intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure
      survival, but by favoring the development of certain organs over that of others,
      this leads to persistent alterations in the growth and function of developing
      tissues. This concept has been somewhat controversial, however recent
      epidemiological, clinical, and animal studies provide support for the
      developmental origins of disease hypothesis. Underlying mechanisms include
      reprogramming of the hypothalamic-pituitary-adrenal axis, islet development, and
      insulin signaling pathways. Emerging data suggests that oxidative stress and
      mitochondrial dysfunction may also play a critical role in the pathogenesis of
      type 2 diabetes in individuals who were growth retarded at birth.

PMID- 22980054
TI  - The appropriate use of biomarkers in heart failure.
AB  - Natriuretic peptides and troponins have been extensively studied and used in
      heart failure, and their value has been extensively discussed. Renal markers,
      such as cystasin-C, NGAL, and KIM-1, have shown growing utility in heart failure.
      The activation of compensatory pathways and ongoing hemodynamic changes result in
      the release of biomarkers that can be monitored to chart disease progression and
      possibly target for therapy.

PMID- 22980055
TI  - Evidence-based therapy for heart failure.
AB  - Heart failure (HF) is a major public health problem associated with increased
      morbidity and mortality. As the US life expectancy increases and the population
      ages, the overall prevalence of HF will continue to escalate. The increasing use
      of effective selective therapies such as neurohormonal blockade in the treatment
      of patients with HF has led to considerable improvement in their prognosis.
      During the past several decades, some studies have demonstrated the benefits of
      treatment; based on the evidence available from these studies, various national
      and international guidelines have specific recommendations for the evidence-based
      therapy with these drugs in patients with HF.

PMID- 22980056
TI  - Diuretics in heart failure: practical considerations.
AB  - This review discusses the role of diuretics in heart failure by focusing on
      different classifications and mechanisms of action. Pharmacodynamic and
      pharmacokinetic properties of diuretics are elucidated. The predominant
      discussion highlights the use of loop diuretics, which are the most commonly used
      drugs in heart failure. Different methods of using this therapy in different
      settings along with a comprehensive review of the side-effect profile are
      highlighted. Special situations necessitating adjustment and the phenomenon of
      diuretic resistance are explained.

PMID- 22980057
TI  - Inotropic therapy: an important role in the treatment of advanced symptomatic
      heart failure.
AB  - Inotropic therapy remains an option in the management of patients with advanced
      heart failure symptoms from systolic dysfunction who do not respond to
      conventional therapies. The decision to use this class is largely predicated on
      an accurate evaluation of the patient's fluid and perfusion status. Selection of
      the appropriate agent and dosing regimens requires an understanding of the
      underlying pathophysiology of heart failure and concomitant therapy. Most
      important, the goals of care should be stated clearly, given inherent risks
      associated with this class of drug.

PMID- 22980058
TI  - Renal dysfunction in heart failure.
AB  - Renal dysfunction is a common, important comorbidity in patients with both
      chronic and acute heart failure (HF). Chronic kidney disease and worsening renal
      function (WRF) are associated with worse outcomes, but our understanding of the
      complex bidirectional interactions between the heart and kidney remains poor.
      When addressing these interactions, one must consider the impact of intrinsic
      renal disease resulting from medical comorbidities on HF outcomes. WRF may result
      from any number of important processes. Understanding the role of each of these
      factors and their interplay are essential in understanding how to improve
      outcomes in patients with renal dysfunction and HF.

PMID- 22980059
TI  - Management of comorbid conditions in heart failure: a review.
AB  - Multiple comorbidities are common in patients in heart failure. Some of them
      could contribute to the underlying development of heart failure, whereas others
      may lead to disease progression and may be associated with poor prognosis. It is
      not only important to diagnose those comorbid conditions early, but also vital to
      treat those conditions appropriately, which may have a huge impact on the primary
      disease itself. The common conditions are discussed in this review, but there are
      multiple other comorbidities beyond the scope of this article. The physician
      should try treating "patients as a whole" instead of treating the specific
      disease, and this approach may require multidisciplinary care.

PMID- 22980060
TI  - Atrial fibrillation in heart failure.
AB  - Heart failure (HF) and atrial fibrillation (AF) are highly prevalent debilitating
      conditions that often coexist and are frequently encountered in clinical
      practice. The presence of chronic AF is a marker of worse prognosis in patients
      with HF, and the onset of new AF in those with chronic HF is associated with
      increased morbidity and mortality. Advances in the development of novel drugs,
      nonpharmacologic modalities, and therapeutic strategies, as well the increased
      understanding of the pathobiology of HF and AF, are key to mitigating the
      tremendous public health burden that is associated with these conditions.

PMID- 22980061
TI  - Breast cancer therapies and cardiomyopathy.
AB  - The prevalence of chemotherapy-related cardiac disease is increasing and
      management demands a multidisciplinary approach from cardiologists and
      oncologists. Pretreatment identification of predisposing risk factors and
      assessment of cardiac function before and at intervals during and after therapy
      with cardiotoxic agents are necessary. In clinical practice, surveillance is
      largely performed using transthoracic echocardiography or multi-gated
      radionuclide angiography. Imaging strategies that detect cardiac injury before
      overt left ventricular systolic dysfunction provide an opportunity for early
      intervention and improved cardiac outcomes.

PMID- 22980062
TI  - Heart failure: a common and complex clinical syndrome.

PMID- 22980063
TI  - Edge-to-edge repair for prevention and treatment of mitral valve systolic
      anterior motion.
AB  - BACKGROUND: The edge-to-edge technique has been proposed to prevent systolic
      anterior motion (SAM) of the mitral valve. There is limited clinical data
      available on outcomes of this technique for this indication. We reviewed the
      midterm results of this technique for SAM prevention and treatment. METHODS: A
      total of 2226 patients had mitral valve repair between 2000 and 2011, 1148 of
      which were for myxomatous mitral regurgitation. Beginning in 2000, predictability
      of postrepair SAM based on the prebypass, intraoperative transesophageal
      echocardiogram arose in our program. The edge-to-edge technique was used in 65
      patients (5.7%) for SAM management, in 53 patients preemptively for
      transesophageal echocardiogram-based SAM prediction, and in 12 patients for
      postrepair SAM treatment. RESULTS: There was no operative mortality.
      Postoperative mitral regurgitation was significantly improved in all patients
      compared with the preoperative grade (P < .001). SAM was completely eliminated,
      the mean mitral regurgitation grade in the postoperative period was 0.7 +/- 0.9,
      and the mean transmitral gradient was 1.3 +/- 2.2 mm Hg. During a mean follow-up
      of 26 months, 1 patient in the SAM treatment group presented late recurrence of
      SAM and no patients developed mitral stenosis (mean transmitral gradient, 2.0 +/-
      2.6 mm Hg; P = .12). Without SAM prediction and preemptive edge-to-edge
      technique, the expected rate of SAM would have been 5.7%; however, the observed
      rate was 1% (12 of 1148 patients). CONCLUSIONS: Initiating an expectation for
      prebypass SAM prediction, combined with a surgical SAM prevention strategy,
      resulted in a reduced prevalence of SAM compared with our model of observed to
      expected-ratios and to published norms.

PMID- 22980064
TI  - Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence
      of hypertension late after coarctation repair in patients with hypoplastic
      arches.
AB  - OBJECTIVES: To determine by 24-hour blood pressure monitoring the risk of
      hypertension late after coarctation repair in patients with arch hypoplasia.
      METHODS: Sixty-two of 116 consecutive patients (age, >=10 years) who had
      coarctation repair and were quoted subjectively by the surgeon or the
      cardiologist to have arch hypoplasia at the time of the repair underwent a
      transthoracic echocardiogram and 24-hour blood pressure monitoring. Median age at
      repair was 11 days (range, 6-48 days). Mean preoperative z score of the proximal
      transverse arch was -2.43 +/- 0.46. Eight patients had a repair via sternotomy (6
      end-to-side anastomoses, 2 patch repairs) and 54 had a conventional repair via
      thoracotomy. RESULTS: After a follow-up of 18 +/- 5 years, 27% of the patients
      (17/62) had resting hypertension and 60% (37/62) had abnormal ambulatory blood
      pressure. Sensitivity of high resting blood pressure in detecting an abnormal 24
      hour ambulatory blood pressure was 41%. Twenty patients had arch obstruction at
      last follow-up. Eighteen of them (90%) had abnormal ambulatory blood pressure.
      None of the patients operated on with end-to-side repair via sternotomy had
      reobstruction compared with 33% (18/54) of those repaired via thoracotomy.
      CONCLUSIONS: Patients with a hypoplastic arch operated via thoracotomy have an
      alarming prevalence of hypertension. Regular follow-up with 24-hour ambulatory
      blood pressure monitoring is warranted, especially in patients who have had a
      smaller aortic arch at the time of the initial operation.

PMID- 22980065
TI  - Mechanical preconditioning enables electrophysiologic coupling of skeletal
      myoblast cells to myocardium.
AB  - OBJECTIVE: The effect of mechanical preconditioning on skeletal myoblasts in
      engineered tissue constructs was investigated to resolve issues associated with
      conduction block between skeletal myoblast cells and cardiomyocytes. METHODS:
      Murine skeletal myoblasts were used to generate engineered tissue constructs with
      or without application of mechanical strain. After in vitro myotube formation,
      engineered tissue constructs were co-cultured for 6 days with viable embryonic
      heart slices. With the use of sharp electrodes, electrical coupling between
      engineered tissue constructs and embryonic heart slices was assessed in the
      presence or absence of pharmacologic agents. RESULTS: The isolation and expansion
      procedure for skeletal myoblasts resulted in high yields of homogeneously desmin
      positive (97.1% +/- 0.1%) cells. Mechanical strain was exerted on myotubes within
      engineered tissue constructs during gelation of the matrix, generating
      preconditioned engineered tissue constructs. Electrical coupling between
      preconditioned engineered tissue constructs and embryonic heart slices was
      observed; however, no coupling was apparent when engineered tissue constructs
      were not subjected to mechanical strain. Coupling of cells from engineered tissue
      constructs to cells in embryonic heart slices showed slower conduction velocities
      than myocardial cells with the embryonic heart slices (preconditioned engineered
      tissue constructs vs embryonic heart slices: 0.04 +/- 0.02 ms vs 0.10 +/- 0.05
      ms, P = .011), lower maximum stimulation frequencies (preconditioned engineered
      tissue constructs vs embryonic heart slices: 4.82 +/- 1.42 Hz vs 10.58 +/- 1.56
      Hz; P = .0009), and higher sensitivities to the gap junction inhibitor
      (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 +/-
      0.07 mmol/L vs 0.93 +/- 0.15 mmol/L; P = .0004). CONCLUSIONS: We have generated
      skeletal myoblast-based transplantable grafts that electrically couple to
      myocardium.

PMID- 22980066
TI  - Significance of force transfer in mitral valve-left ventricular interaction: in
      vivo assessment.
AB  - OBJECTIVE: The objective of this study was to assess the combined force transfer
      from the papillary muscle tips to the mitral valve through the chordae tendineae
      in vivo, and thereby quantify the force transmitted through the papillary-chordal
      complex to augment left ventricular ejection. METHODS: In an acute porcine model
      (n = 8), force transfer between papillary muscles and the mitral valve was
      recorded on the anterior and posterior papillary muscle tip using dedicated force
      transducers. Ultrasound sonomicrometry was utilized to record and calculate left
      ventricular long-axis shortening and mitral annular geometry. The closing force
      acting on the mitral valve leaflets was calculated as mitral annular area
      multiplied by the transmitral pressure difference throughout systole. Mitral
      valve competence was verified before measurements with color Doppler ultrasound.
      RESULTS: Peak force in the anterior and posterior papillary muscle was 5.9 +/-
      0.6 N and 5.8 +/- 0.7 N (mean +/- standard error of the mean), respectively, and
      peak closing force was 6.8 +/- 0.3 N all at a transmitral pressure of 90 mm Hg.
      Peak rate of left ventricular contraction coincided with peak papillary muscle
      force. CONCLUSIONS: This study is the first to assess the magnitude and time
      course of the longitudinal force transmitted through the papillary-chordal
      complex to the left ventricular wall during ejection. The study also demonstrates
      a significant force transfer to the closing force acting on the mitral valve
      leaflets that constitutes an essential component of valvular-ventricular
      interaction to enhance left ventricular systolic pump performance. The magnitude
      of the combined papillary muscle force component emphasizes the crucial role of
      preserving mitral valve-left ventricular continuity in mitral valve surgery.

PMID- 22980067
TI  - Discussion.

PMID- 22980068
TI  - Identification and characterization of stemlike cells in human esophageal
      adenocarcinoma and normal epithelial cell lines.
AB  - OBJECTIVE: Recent studies have suggested that human solid tumors may contain
      subpopulations of cancer stem cells with the capacity for self-renewal and the
      potential to initiate and maintain tumor growth. The aim of this study was to use
      human esophageal cell lines to identify and characterize putative esophageal
      cancer stem cell populations. METHODS: To enrich stemlike cells, Het-1A (derived
      from immortalized normal esophageal epithelium), OE33, and JH-EsoAd1 (each
      derived from primary esophageal adenocarcinomas) were cultured using serum-free
      media to form spheres. A comprehensive analysis of parent and spheroid cells was
      performed by flow cytometry, Western blot analysis, immunohistochemistry and
      polymerase chain reaction array to study cancer stem cell-related genes, colony
      formation assays to assess clonogenicity, xenotransplantation to assess
      tumorigenicity, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assays to assess chemosensitivity to 5-fluorouracil and cisplatin. RESULTS: For
      all cell lines, clonogenicity, tumorigenicity, and chemoresistance to 5
      fluorouracil and cisplatin were significantly higher than for spheroid cells
      compared with parent cells. Spheroids exhibited an increased frequency of cells
      expressing integrin alpha6(bri)/CD71(dim), and Achaete-scute complex homolog 2
      messenger RNA and protein were also significantly overexpressed in spheroid cells
      compared with parent cells. CONCLUSIONS: The higher clonogenicity,
      tumorigenicity, and drug resistance exhibited by spheroids derived from Het-1A,
      OE33, and JH-EsoAd1 reflects an enrichment of stemlike cell populations within
      each esophageal cell line. Esophageal cells enriched for integrin
      alpha6(bri)/CD71(dim) and/or overexpressing Achaete-scute complex homolog 2 would
      appear to represent at least a subpopulation of stemlike cells in Het-1A, OE33,
      and JH-EsoAd1.

PMID- 22980069
TI  - Discussion.

PMID- 22980070
TI  - Discussion.

PMID- 22980071
TI  - Assessing the Organizational Social Context (OSC) of child welfare systems:
      implications for research and practice.
AB  - OBJECTIVE: The study: (1) provides the first assessment of the a priori
      measurement model and psychometric properties of the Organizational Social
      Context (OSC) measurement system in a US nationwide probability sample of child
      welfare systems; (2) illustrates the use of the OSC in constructing norm-based
      organizational culture and climate profiles for child welfare systems; and (3)
      estimates the association of child welfare system-level organizational culture
      and climate profiles with individual caseworker-level job satisfaction and
      organizational commitment. METHODS: The study applies confirmatory factor
      analysis (CFA) and hierarchical linear models (HLM) analysis to a US nationwide
      sample of 1,740 caseworkers from 81 child welfare systems participating in the
      second National Survey of Child and Adolescent Wellbeing (NSCAW II). The
      participating child welfare systems were selected using a national probability
      procedure reflecting the number of children served by child welfare systems
      nationwide. RESULTS: The a priori OSC measurement model is confirmed in this
      nationwide sample of child welfare systems. In addition, caseworker responses to
      the OSC scales generate acceptable to high scale reliabilities, moderate to high
      within-system agreement, and significant between-system differences. Caseworkers
      in the child welfare systems with the best organizational culture and climate
      profiles report higher levels of job satisfaction and organizational commitment.
      Organizational climates characterized by high engagement and functionality, and
      organizational cultures characterized by low rigidity are associated with the
      most positive work attitudes. CONCLUSIONS: The OSC is the first valid and
      reliable measure of organizational culture and climate with US national norms for
      child welfare systems. The OSC provides a useful measure of Organizational Social
      Context for child welfare service improvement and implementation research efforts
      which include a focus on child welfare system culture and climate.

PMID- 22980072
TI  - Skeletal abnormalities of the upper limbs--neonatal diagnosis of 49,XXXXY
      syndrome.
AB  - A case of neonatal diagnosis of 49,XXXXY syndrome is presented. Clinical
      identification was prompted by a bilateral thickening of the radioulnar joints
      and X-ray imaging disclosing almost complete radioulnar synostosis. Conventional
      karyotyping was initiated and revealed a karyotype of 49,XXXXY. Previously
      reported neonatal symptoms such as low birth weight, muscular hypotonia, or
      genital malformations were absent in this case. Microsatellite analysis showed
      two different X chromosomes each present in two copies, supporting that the four
      X chromosomes had arisen from a nondisjunction in maternal meiosis I followed by
      a second nondisjunction involving both X chromosomes in meiosis II.
      Multidisciplinary follow-up was organised to ensure timely recognition of
      associated complications. Early awareness of the diagnosis may offer a potential
      benefit regarding outcome.

PMID- 22980073
TI  - Cognitive development from two to ten years after pediatric epilepsy surgery.
AB  - The development of cognitive functions and the sustainability of seizure control
      between two and ten years after epilepsy surgery were prospectively investigated
      in 17 children and adolescents. Intelligence quotient remained stable. Learning
      capacity improved. Verbal memory improved in half of the subjects and declined in
      half, whereas figurative memory declined in most patients. Working memory
      improved as did attention regarding sustained attention and impulse control. In
      contrast, reaction times were longer, and the auditory attention span was
      shorter. Executive functions were not affected. Six subjects (35%) were seizure
      free at the 10-year follow-up, and a seizure reduction of more than 75% had been
      achieved in 13 (76%). Seizure control improved in five and seizures recurred in
      two subjects between the two- and the 10-year follow-up.

PMID- 22980074
TI  - "Ictal epileptic headache": beyond the epidemiological evidence.

PMID- 22980075
TI  - The psychoeducational program for children with epilepsy and their parents
      (FAMOSES): results of a controlled pilot study and a survey of parent
      satisfaction over a five-year period.
AB  - Feasibility of the educational program FAMOSES (modular service package epilepsy
      for families) was evaluated in a controlled pilot study. Parents of children with
      epilepsy from epilepsy centers in Germany were allocated to either educational
      group (treatment group, n=55) or waiting-list group (control group, n=48).
      Questionnaires included epilepsy-specific scales (knowledge, coping, adaptation,
      anxiety, rules and limitations, seizure management, impact of epilepsy).
      Multivariate analysis of variance with repeated measurements indicated
      significant improvements in the treatment group compared to the control group
      (time*group interaction: p<0.01). Univariate analyses (ANOVA) confirmed
      improvements in knowledge (p<0.001), adaptation (p<0.01), epilepsy-related
      anxiety (p<0.05), and seizure management (p<0.05). Surveillance as well as
      seizure frequency (p<0.05) of children whose parents participated in the
      treatment group was reduced (p<0.05). Furthermore, parents' satisfaction with the
      content and interactive didactic format of the program was assessed in a survey
      with 852 parents over a five-year period. This survey showed an improvement over
      the course of time (p<0.05). Feasibility and need for the educational program
      were confirmed.

PMID- 22980076
TI  - Screening for major depressive episodes in Japanese patients with epilepsy:
      validation and translation of the Japanese version of Neurological Disorders
      Depression Inventory for Epilepsy (NDDI-E).
AB  - We validated and translated into Japanese the English version of the screening
      instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to
      identify major depressive episodes in patients with epilepsy. A total of 159
      Japanese subjects with epilepsy underwent a psychiatric structured interview with
      the Japanese version of the Mini International Neuropsychiatric Interview
      (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J).
      Twelve participants met the M.I.N.I.-J criteria of current major depressive
      episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's
      alpha coefficient was 0.83 and a cut-off score greater than 16 provided a
      sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of
      0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for
      major depressive episodes in epilepsy patients. Routine use of this brief and
      self-administered instrument in busy clinical settings will likely improve
      management of depression in Japanese individuals with epilepsy.

PMID- 22980077
TI  - Familial epilepsy in the pharaohs of ancient Egypt's eighteenth dynasty.
AB  - The pharaohs of Egypt's famous eighteenth dynasty all died early of unknown
      causes. This paper comprehensively reviews and analyses the medical literature
      and current evidence available for the New Kingdom rulers - Tuthmosis IV,
      Amenhotep III, Akhenaten, Smenkhkare and Tutankhamun. The integration of these
      sources reveals that the eighteenth dynasty rulers may have suffered from an
      inherited condition that may explain their untimely deaths. The description of
      recurring strong religious visions, likely neurological disease and gynecomastia,
      supports the theory that these pharaohs may have suffered from a familial
      temporal epilepsy syndrome that ultimately led to their early downfall.

PMID- 22980078
TI  - Epilepsy, unawareness of seizures and driving license: the potential role of 24
      hour ambulatory EEG in defining seizure freedom.
AB  - INTRODUCTION: Seizures represent a potential source of accidents/death.
      Permission to drive may, therefore, be granted in a seizure-free period. Laws and
      regulations regarding this issue vary widely, and the onus of reporting seizures
      ultimately rests on the individual. Unfortunately, as some patients are unaware
      of their seizures, their reports may be unreliable. METHODS: In this
      retrospective study, we selected, from a group of 1100 consecutive patients, 57
      cases (26 males/31 females; mean age: 42.5 years) in whom the AEEG documented
      ictal events (UIEs) not reported in a self-kept diary. By means of a simple
      questionnaire, we interviewed all these patients to collect information on
      driving licenses. We, thus, assessed how many of these patients (both drug
      resistant and seizure free) drove regularly. RESULTS: Our study shows a
      relatively large number of patients with epilepsy and UIEs. Fifteen patients
      suffered from idiopathic generalized epilepsy (IGE) while 42 had partial epilepsy
      (PE). The patients were seizure free in 21 cases and 36 had drug-resistant
      seizures. Many patients in both these subgroups had a driving license and drove
      normally (active driving in 12/36 drug-resistant patients and in 18/21 seizure
      free patients). Worthy of note is the finding that an "apparently" seizure-free
      group of patients drove regularly. CONCLUSIONS: This study revealed a large
      number of patients (both drug resistant and seizure free) with AEEG-documented
      UIEs. This finding highlights the usefulness of AEEG in clinical practice as a
      means of more accurately ascertaining seizure freedom and supporting decisions
      involving the renewal or granting of a driving license.

PMID- 22980080
TI  - fMRI of verbal and nonverbal memory processes in healthy and epileptogenic medial
      temporal lobes.
AB  - Material-specific memory impairments are a well-established consequence of
      unilateral medial temporal lobe damage. We used fMRI to investigate encoding and
      recognition of verbal and nonverbal stimuli using adaptations of tasks used
      successfully in clinical evaluations of patients with temporal lobe epilepsy
      (TLE). We studied two patient groups, one with left TLE and one with right TLE,
      and one group of healthy subjects. Results from the healthy subjects indicated
      that initial and delayed recognition trials of the verbal task activated the left
      medial temporal lobe, and the same tasks of the nonverbal task activated the
      right, confirming the sensitivity to laterality of our clinical tasks. Patients
      tended to use the opposite hippocampus, but often the parahippocampal gyrus on
      the same side, compared to the healthy subjects. Since our patients and the
      healthy groups performed similarly on the memory tasks, we conclude that the
      patients' activation patterns represent an effective adaptation to the presence
      of an unhealthy hippocampus.

PMID- 22980079
TI  - Decreased language laterality in tuberous sclerosis complex: a relationship
      between language dominance and tuber location as well as history of epilepsy.
AB  - Nearly 90% of patients with tuberous sclerosis complex (TSC) have epilepsy.
      Epilepsy surgery can be considered, which often requires a presurgical assessment
      of language lateralization. This is the first study to investigate language
      lateralization in TSC patients using magnetoencephalography. Fifteen patients
      performed a language task during magnetoencephalography recording. Cerebral
      generators of language-evoked fields (EF) were identified in each patient.
      Laterality indices (LI) were computed using magnetoencephalography data extracted
      from the inferior frontal as well as middle and superior temporal gyri from both
      hemispheres between 250 and 550 ms. Source analysis demonstrated a fusiform gyrus
      activation, followed by an activation located in the basal temporal language area
      and middle and superior temporal gyri responses, ending with an inferior frontal
      activation. Eleven patients (73.3%) had left-hemisphere language dominance,
      whereas four patients (26.7%) showed a bilateral language pattern, which was
      associated with a history of epilepsy and presence of tubers in language-related
      areas.

PMID- 22980082
TI  - Advances in modeling of the bovine estrous cycle: synchronization with PGF2alpha.
AB  - Our model of the bovine estrous cycle is a set of ordinary differential equations
      which generates hormone profiles of successive estrous cycles with several
      follicular waves per cycle. It describes the growth and decay of the follicles
      and the corpus luteum, as well as the change of the key reproductive hormones,
      enzymes and processes over time. In this work we describe recent developments of
      this model towards the administration of prostaglandin F2alpha. We validate our
      model by showing that the simulations agree with observations from
      synchronization studies and with measured progesterone data after single dose
      administrations of synthetic prostaglandin F2alpha.

PMID- 22980081
TI  - Acquired epileptiform opercular syndrome: F-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET) findings and efficacy of levetiracetam therapy.
AB  - We report a five-year-old girl presenting with dysphagia, dysarthria, drooling,
      and generalized tonic convulsions in whom the final diagnosis was acquired
      epileptiform opercular syndrome. Levetiracetam monotherapy at a dosage of 40
      mg/kg/day improved the clinical findings, and seizures were controlled at the end
      of the first month of treatment. Six months after the initial diagnosis, she
      presented with speech deterioration and dysarthria. At this time, although sleep
      and awake electroencephalography (EEG) were normal, FDG-PET showed hypometabolic
      and hypermetabolic regions in the anterior/inferior and anterior regions of the
      right frontal lobe, respectively. By increasing before levetiracetam dosage to 50
      mg/kg/day, the clinical findings resolved and the patient is still seizure free.
      Acquired epileptiform opercular syndrome is a rare epileptic disorder in which
      the seizures are resistant to conventional antiepileptic drugs. Levetiracetam may
      be an effective antiepileptic drug in controlling seizures and other clinical
      findings in acquired opercular epileptiform syndrome. Hypometabolic and
      hypermetabolic regions in FDG-PET study may be due to ongoing seizure activity or
      impaired glucose metabolism in this disorder.

PMID- 22980083
TI  - The cardiac biomarkers troponin I and CK-MB in nonpregnant and pregnant goats,
      goats with normal birth, goats with prolonged birth, and goats with pregnancy
      toxemia.
AB  - This study was designed to establish the reference range for the cardiac
      biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB)
      in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged
      birth associated with dystocia, and goats with pregnancy toxemia. Fifty-seven
      does, categorized into three groups (G1 to G3), were used. These groups were
      comprised of 20 healthy does (G1), 19 does with prolonged birth (G2), and 18 does
      with pregnancy toxemia (G3). Six blood samples (T0 to T5) were collected from G1.
      The first blood sample (T0) was taken before insemination, the second (T1) at the
      first trimester, the third (T2) at the second trimester, the fourth (T3) at the
      last trimester, the fifth (T4) within 12 h of parturition, and the sixth blood
      sample (T5) was taken 10 days after parturition. A sample of blood was obtained
      from G2 and G3 upon admission to the hospital. At T0 to T3, no cTnI was detected
      in any of the 20 does in G1. At parturition (T4), seven of the 20 goats (35%)
      exhibited slightly elevated cTnI concentrations (range, 0.01 to 0.04 ng/mL). Ten
      days after parturition (T5), cTnI was not detected in any of the 20 goats. In 10
      of the 19 goats (53%) with prolonged birth (G2), the cTnI was significantly
      elevated to a mean value of 0.094 +/- 0.155 ng/mL, with a maximum value of 0.61
      ng/mL. In 16 of the 18 goats (89%) with pregnancy toxemia (G3), the cTnI was
      significantly elevated to a value of 0.852 +/- 1.472 ng/mL, with a maximum value
      of 5.219 ng/mL. Comparing the values of CK-MB in G1 (T0 to T5), G2 and G3
      revealed nonsignificant differences. Only a slight elevation in the CK-MB levels
      in goats with prolonged birth (G2) was noted. We concluded that in healthy does,
      the cardiac biomarker cTnI is not elevated during normal pregnancy. The serum
      cTnI concentration may be elevated in a number of goats at normal vaginal or
      cesarean delivery. Finally, cTnI is significantly elevated in does with pregnancy
      toxemia and could be used as a prognostic indicator in such cases. The cardiac
      biomarker CK-MB is not a good indicator of parturition stress in does. Serum cTnI
      is elevated in goats with pregnancy toxemia, indicating some degree of cardiac
      dysfunction.

PMID- 22980084
TI  - Reproductive and economic impact following controlled introduction of cattle
      persistently infected with bovine viral diarrhea virus into a naive group of
      heifers.
AB  - The reproductive impact following controlled introduction of animals persistently
      infected (PI) with bovine viral diarrhea virus (BVDV) was evaluated in BVDV-naive
      heifers. Heifers were randomly allocated into two groups: an unexposed control
      herd (n = 34) and a herd exposed to five persistently infected (PI) animals for 7
      mo, beginning 50 days before the breeding season (n = 34). Initiation of the BVDV
      challenge was timed to mimic either direct contact with PI calves born in the
      previous calving season or accidental introduction of PI herd additions prior to
      the breeding season. The PI animals represented BVDV Types 1a (n = 3), 1b (n = 1)
      and 2 (n = 1). Two BVDV-free, seropositive bulls were used in each group for 78
      days breeding seasons. In both groups, 33 of 34 heifers became pregnant, with
      similar distribution of fetal ages. Two heifers in each group aborted (etiology
      undetermined). In addition, one calf was born dead and one calf died 3 days post
      partum in the BVDV-exposed group. One calf in the unexposed group died 4 mo post
      partum. No calves, including the stillborn calf and the two calves that died
      prior to weaning, were persistently infected with BVDV. In summary, introduction
      of PI cattle to a group of BVDV-naive heifers 50 days prior to the breeding
      season did not negatively impact reproductive performance. To the contrary, the
      active immunity that developed following field exposure to BVDV provided
      effective reproductive and fetal protection during the breeding season and
      subsequent gestations, despite continuous exposure to PI animals until
      approximately midgestation. Although BVDV can have potentially devastating
      reproductive effects, timing of infection is a critical determinant in the
      outcome of a BVDV infection. A controlled breeding season with introduction of
      herd additions at less critical reproductive time points can mitigate the
      negative reproductive health consequences of BVDV.

PMID- 22980085
TI  - Melatonin suppresses apoptosis and stimulates progesterone production by bovine
      granulosa cells via its receptors (MT1 and MT2).
AB  - Melatonin and its receptors have been detected in the ovary of many species, and
      mediate ovarian functions. The present study was designed to investigate the
      expression and subcellar location of melatonin receptors in bovine granulosa
      cells (GCs), using reverse transcription (RT) polymerase chain reaction, Western
      blot, and immunofluorescence analyses. Furthermore, expression level of melatonin
      receptors mRNA (real-time polymerase chain reaction) after treatment with various
      concentrations of melatonin, as well as its effects on cell apoptosis,
      proliferation, and steroidogenesis (by flow cytometry and RIA), were determined.
      In bovine GCs, melatonin receptors MT1 and MT2 were differentially located at the
      cell membrane, the cytoplasm, and nuclear membranes. The expression of MT1 and
      MT2 mRNA was regulated differently by melatonin in time- and dose-dependent
      manners. Exogenous melatonin suppressed cell apoptosis (P < 0.05) but not
      proliferation (P > 0.05). After 72 h, the apoptotic rate was significantly
      inhibited in all treatment groups. Meanwhile, melatonin supplementation
      stimulated progesterone production, but inhibited estradiol biosynthesis, in a
      time-dependent manner. Progesterone production was highest (P < 0.05) at 72 h.
      Estradiol concentrations were almost unaffected (P > 0.05) at 24 h, but were
      decreased (P < 0.05) at 48 h. In conclusion, exogenous melatonin acts via
      receptors and has important roles in regulation of development and function of
      bovine GCs.

PMID- 22980086
TI  - Impact of a novel inactivated PRRS virus vaccine on virus replication and virus
      induced pathology in fetal implantation sites and fetuses upon challenge.
AB  - Preventing congenital infection is important for the control of porcine
      reproductive and respiratory syndrome (PRRS). Recently, in our laboratory, an
      inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine
      has been developed. Promising results in young pigs encouraged us to test the
      vaccine potency to prevent congenital infection. In the present study, the
      performance of this experimental inactivated vaccine was investigated in pregnant
      gilts. An advanced protocol was used to test the PRRSV vaccine efficacy. This
      protocol is based on recent insights in the pathogenesis of congenital PRRSV
      infections. Three gilts were vaccinated with an experimental PRRSV 07V63
      inactivated vaccine at 27, 55, and 83 days of gestation. Three unvaccinated gilts
      were included as controls. At 90 days of gestation, all animals were intranasally
      inoculated with 10(5) tissue culture infectious dose 50 (TCID(50)) of PRRSV
      07V63. Twenty days postchallenge animals were euthanized and sampled. The
      vaccinated gilts quickly developed virus neutralizing (VN) antibodies starting
      from 3 to 7 days postchallenge (1.0 to 5.0 log2). In contrast, the unvaccinated
      gilts remained negative for VN antibodies after challenge. The vaccinated gilts
      had shorter viremia than the control gilts. Gross pathology (mummification) was
      observed in 8% of the fetuses from vaccinated gilts and in 15% of the fetuses
      from unvaccinated gilts. The number of fetuses with severe microscopic lesions in
      the fetal implantation sites (a focal detachment of the trophoblast from the
      uterine epithelium; a focal, multifocal, or full degeneration of the fetal
      placenta) was lower in the vaccinated (19%) versus unvaccinated (45%) gilts (P <
      0.05). The number of PRRS-positive cells in the fetal placentae was higher in
      unvaccinated versus vaccinated gilts (P < 0.05). In contrast, the number of PRRS
      positive cells in the myometrium/endometrium was higher in vaccinated versus
      unvaccinated gilts (P < 0.05). Fifty-seven percent of the fetuses from the
      vaccinated gilts and 75% of the fetuses from the unvaccinated gilts were PRRSV
      positive. In conclusion, implementation of the novel experimental inactivated
      PRRSV vaccine primed the VN antibody response and slightly reduced the duration
      of viremia in gilts. It also reduced the number of virus-positive fetuses and
      improved the fetal survival, but was not able to fully prevent congenital PRRSV
      infection. The reduction of fetal infection and pathology is most probably
      attributable to the vaccine-mediated decrease of PRRSV transfer from the
      endometrium to the fetal placenta.

PMID- 22980087
TI  - Survival of emu (Dromaius novaehollandiae) sperm preserved at subzero
      temperatures and different cryoprotectant concentrations.
AB  - Three experiments were conducted to optimize the protocol for cryopreservation of
      emu sperm. Ejaculates were collected from trained male emus then diluted 1:1 and
      pooled before allocation to treatments and measured for sperm viability,
      motility, egg membrane penetration ability, membrane stability, and morphology.
      In Experiment 1, semen was either cooled to 5  degrees C after dilution or
      diluted with a precooled to 5  degrees C diluent before cooling to 5  degrees C
      and then frozen at liquid nitrogen vapor temperatures of -140  degrees C and -35 
      degrees C, with 6% or 9% dimethylacetmide (DMA; a permeating cryoprotectant) and
      compared for sperm functions. The percentages of viable (42.8 +/- 1.1%), normal
      (39.0 +/- 1.3%), and motile (29.8 +/- 1.3%) sperm were higher (P < 0.001) for
      semen frozen at -14  degrees C with 9% DMA (path 2) than for all other
      combinations. In Experiment 2, we assessed the value of combining DMA and
      trehalose in the diluent. Combining trehalose (3% to 9%) with DMA (3% to 9%)
      prior to freezing reduced (P < 0.001) the percentages of postthaw viable (by 4 to
      9 +/- 1.2%), normal (by 5 to 11 +/- 1.3%), and motile sperm (by 13 to 17 +/-
      2.5%) and the number of holes on the perivitelline layer (by 27 to 29
      holes/mm(2)). Postthaw function was best preserved with 9% DMA alone. In
      experiment 3, we investigated the possibility of increasing DMA concentrations
      from 6% to 24%. Postthaw sperm viability (52 to 55 +/- 2.3%) and morphology (48
      to 51 +/- 1.7%) were higher (P < 0.05) with 18% and 24% than with 6% to 12% DMA
      and did not differ between 18% and 24% DMA. However, sperm motility (36 to 43 +/-
      2.9%) and the number of perivitelline holes were similar (P > 0.05) for 9% to 18%
      DMA (36 to 55 +/- 12%). We concluded that adding 6% to 9% trehalose to the
      diluent offered no advantage, and that the current best practice for preserving
      postthaw function in emu sperm is to dilute semen with a precooled to 5  degrees
      C diluent and use 18% DMA.

PMID- 22980088
TI  - Expression patterns of sirtuin genes in porcine preimplantation embryos and
      effects of sirtuin inhibitors on in vitro embryonic development after
      parthenogenetic activation and in vitro fertilization.
AB  - We examined the expression patterns of porcine sirtuin 1 to 3 (Sirt1-3) genes in
      preimplantation embryos derived from parthenogenetic activation (PA), in vitro
      fertilization (IVF) and somatic cell nuclear transfer (SCNT). We also
      investigated the effects of sirtuin inhibitors (5 mM nicotinamide [NAM] and 100
      MUM sirtinol) on embryonic development of PA and IVF embryos under in vitro
      culture (IVC). The expression patterns of Sirt1-3 mRNA in preimplantation embryos
      of PA, IVF, and SCNT were significantly (P < 0.05) decreased from metaphase stage
      of oocyte to blastocyst stage. Especially, the expressions of Sirt1-3 in SCNT
      blastocysts were significantly (P < 0.05) lower and Sirt2 in PA blastocyst was
      significantly higher compared with the IVF blastocysts. Treatment with sirtuin
      inhibitors during IVC resulted in significantly (P < 0.05) decreased blastocyst
      formation and total cell number of blastocyst derived from PA (NAM: 29.4% and
      29.6, sirtinol: 31.0% and 30.3, and control: 40.9% and 41.7, respectively) and
      IVF embryos (NAM: 10.4% and 30.9, sirtinol: 6.3% and 30.5, and control: 16.7% and
      42.8, respectively). There was no significant difference in cleavage rate in both
      PA and IVF embryos. The early and expanded blastocyst formations at Day 7 were
      significantly lower in the sirtuin inhibitors-treated groups than the control. It
      was demonstrated that sirtuin inhibitor (NAM) influenced the percentage of
      blastocyst formation and total cell number of PA derived blastocyst when NAM was
      added during day 4 to 7 (22.1% and 32.4) or day 0 to 7 (23.1% and 31.6) of IVC
      compared with the control (41.8% and 41.5). No significant difference in cleavage
      rates appeared among the groups. The blastocysts derived from PA embryos treated
      with sirtuin inhibitors showed lower (P < 0.05) expressions of POU5F1 and Cdx2
      genes. Also, Sirt2 mRNA expression was significantly decreased in sirtinol
      treated group and Sirt3 mRNA expression was also significantly decreased in both
      NAM and sirtinol treated groups compared with the control. In conclusion, these
      results suggest that sirtuins may have a physiological and important role in
      embryonic development of porcine preimplantation embryos by regulating essential
      gene expressions of developing embryos. These findings could have implications
      for understanding the role of sirtuins during embryo development and for
      improving SCNT and related techniques.

PMID- 22980089
TI  - Delayed uterine fluid clearance and reduced uterine perfusion in bitches with
      endometrial hyperplasia and clinical management with postmating antibiotic.
AB  - In many species a transient uterine inflammatory response follows mating and is
      proposed to remove excess spermatozoa, bacteria, and other contaminants from the
      uterus. Similar events have been documented in the bitch involving increased
      uterine contractions, polymorphonuclear neutrophil influx and uterine artery
      vasodilation. Some healthy bitches with endometrial hyperplasia have increased
      numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced
      fertility; it is purported that this represents a presumed postmating
      endometritis. This study used B-mode and Doppler ultrasonography at the time of
      mating to measure uterine contractions, clearance of ejaculated fluid, and
      uterine artery velocity in normal bitches and those with endometrial hyperplasia.
      Mating resulted in an increase in the number of uterine contractions, although
      fewer mating-induced contractions were noted in bitches with endometrial
      hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after
      mating from the bitches with endometrial hyperplasia than the normal bitches (P =
      0.01). In a further study, Doppler ultrasonography showed that in normal bitches
      there was a significant increase in uterine artery blood velocity (P = 0.04) and
      a decrease in the resistance index after mating (P = 0.04), indicating
      vasodilation. In bitches with endometrial hyperplasia the baseline resistance
      index was significantly higher than normal bitches (P = 0.05), and furthermore,
      although there was a significant decrease in resistance index after mating, in
      the bitches with endometrial hyperplasia this was of a smaller magnitude that in
      normal bitches. These findings indicate lower baseline uterine perfusion, and a
      blunted vasodilation response to mating in bitches with endometrial hyperplasia.
      Short-duration postmating administration of systemic antibiotic increased
      pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes
      in bitches with endometrial hyperplasia were lower than those of normal bitches
      both before and after treatment with postmating antibiotic (P = 0.04 and < 0.01,
      respectively). Mating-induced endometritis in bitches with endometrial
      hyperplasia appears to affect fertility by reducing the uterine vasodilatory
      response to mating and delaying clearance of uterine fluid as a result of
      decreased uterine contractions but the effect can be ameliorated in part by the
      postmating administration of antibiotic.

PMID- 22980090
TI  - Disorders of sexual development and associated changes in the pituitary-gonadal
      axis in dogs.
AB  - Normal sexual differentiation depends on completion of chromosomal sex
      determination, gonadal differentiation, and development of the phenotypic sex. An
      irregularity in any of these three steps can lead to a disorder in sexual
      development (DSD). We examined nine dogs with DSD by abdominal ultrasonography,
      laparotomy, histologic examination of the gonads, and reproductive tract,
      cytogenetic analysis, and mRNA expression of the SRY gene. We also determined the
      plasma concentrations of luteinizing hormone (LH), estradiol-17beta, and
      testosterone before and after administration of gonadotropin-releasing hormone
      (GnRH) and compared these results with those obtained in anestrous bitches and
      male control dogs. The gonads of three dogs with DSD contained both testicular
      and ovarian tissue, while in the other six only testicular tissue was found. Each
      of the dogs had a uterus. Based on gynecologic examination, cytogenetic analysis,
      and the histology of the gonads, seven of the nine dogs appeared to be XX sex
      reversals. Three of these were XX true hermaphrodites and four were XX males; the
      other two dogs had incomplete XY gonadal dysgenesis. All seven XX sex-reversed
      dogs were found to be negative for the SRY gene by polymerase chain reaction. The
      basal plasma luteinizing hormone (LH) concentration was significantly higher in
      dogs with DSD than in anestrous bitches but not significantly different from that
      in male dogs. The basal plasma LH concentration increased significantly after
      GnRH administration in all dogs with DSD. The basal plasma estradiol
      concentration was significantly higher in dogs with DSD than in anestrous bitches
      but not significantly different from that in male dogs. The basal plasma
      testosterone concentration was lower in dogs with DSD than in male dogs. In all
      dogs with DSD both the basal and GnRH-induced plasma testosterone concentrations
      were above the upper limit of their respective ranges in the anestrous bitches.
      In conclusion, the secretion of LH and estradiol in these dogs with DSD, all of
      which had testicular tissue in their gonads, was similar to that in male control
      dogs. These results indicate that the basal and/or GnRH-stimulated plasma
      testosterone concentration might be used to detect the presence of testicular
      tissue in dogs with DSD.

PMID- 22980091
TI  - First live offspring born in superovulated sika deer (Cervus nippon) after embryo
      vitrification.
AB  - The rapid growth in sika deer (Cervus nippon) farming and interest in their
      conservation is an impetus for development of embryo transfer (ET) procedures.
      However, a paucity of research has prevented widespread application of ET in this
      species. The objective of the present study was to establish a multiple ovulation
      and ET procedure with both fresh and vitrified embryos in sika deer. Multiparous
      weaned hinds (N = 18) were used as embryo donors during the reproductive season
      of 2008 at a local breeding farm in China. Estrus was synchronized in donors and
      recipients (N = 38) by inserting a controlled internal drug release for 12 days
      (insertion = Day 0). Superovulation was induced with a total of 320 mg of NIH-FSH
      P1 (Folltropin-V; Bioniche, Belleville, ON, Canada) given as 40 mg im every 12 h
      from the afternoon of Day 9 to the morning of Day 13. After estrus was detected,
      donors were artificially inseminated using a transcervical technique. The embryo
      recovery rate was 76.8% (63/82), including 1.6% (1/63), 77.8% (49/63), and 1.6%
      (1/63) blastocysts, morula, and eight-cell embryos, respectively. After transfer
      of fresh and vitrified embryos, pregnancy rates were 85.7% and 61.6% and birth
      rates were 64.3% and 53.9% (P > 0.05). In conclusion, we developed a satisfactory
      multiple ovulation and ET procedure in farmed sika deer using vitrified embryos.

PMID- 22980092
TI  - A simple and high-throughput method to assess maturation status of bovine
      oocytes: comparison of anti-lamin A/C-DAPI with an aceto-orcein staining
      technique.
AB  - A precise, accurate, nonambiguous and high-throughput method is required to
      assess nuclear maturation of mammalian oocytes. The objectives of this study were
      to compare the efficiency and ease of use of a simplified fluorescence imaging
      (anti-lamin A/C and 4',6-diamidino-2-phenylindole [DAPI]) technique to the
      existing technique (aceto-orcein staining) for the evaluation of nuclear
      maturation of bovine oocytes, and to determine the kinetics of bovine oocyte
      maturation using an anti-lamin A/C-DAPI technique. In Experiment 1, oocytes were
      matured in vitro and stained with aceto-orcein and anti-lamin A/C-DAPI staining
      techniques. The proportions of oocytes lost during procedures and those that
      could not be classified (because of ambiguous morphology) during evaluation were
      lower (P < 0.0001) in oocytes stained with anti-lamin A/C-DAPI (9% and 2%) than
      those stained with aceto-orcein (31% and 13%), respectively. Anti-lamin A/C-DAPI
      was a quick procedure which could be completed within 7 h after completion of the
      maturation (compared with > 24 h for the aceto-orcein method). Furthermore, > 200
      oocytes could be stained in one batch with anti-lamin A/C-DAPI technique. In
      Experiment 2, nuclear maturation kinetics of bovine oocytes at various time
      intervals (0, 6, 12, and 22 h) during in vitro maturation (IVM) was evaluated
      using the anti-lamin A/C-DAPI technique. Germinal vesicle, germinal vesicle
      breakdown, metaphase I, and metaphase II oocytes were predominant at 0, 6, 12,
      and 22 h of IVM, respectively. We concluded that the anti-lamin A/C-DAPI was an
      efficient and simple technique for nonambiguous evaluation of nuclear maturation
      status of large numbers of oocytes in a short interval.

PMID- 22980096
TI  - Computer literacy among first year medical students in a developing country: a
      cross sectional study.
AB  - BACKGROUND: The use of computer assisted learning (CAL) has enhanced
      undergraduate medical education. CAL improves performance at examinations,
      develops problem solving skills and increases student satisfaction. The study
      evaluates computer literacy among first year medical students in Sri Lanka.
      METHODS: The study was conducted at Faculty of Medicine, University of Colombo,
      Sri Lanka between August-September 2008. First year medical students (n = 190)
      were invited for the study. Data on computer literacy and associated factors were
      collected by an expert-validated pre-tested self-administered questionnaire.
      Computer literacy was evaluated by testing knowledge on 6 domains; common
      software packages, operating systems, database management and the usage of
      internet and E-mail. A linear regression was conducted using total score for
      computer literacy as the continuous dependant variable and other independent
      covariates. RESULTS: Sample size-181 (Response rate-95.3%), 49.7% were Males.
      Majority of the students (77.3%) owned a computer (Males-74.4%, Females-80.2%).
      Students have gained their present computer knowledge by; a formal training
      programme (64.1%), self learning (63.0%) or by peer learning (49.2%). The
      students used computers for predominately; word processing (95.6%), entertainment
      (95.0%), web browsing (80.1%) and preparing presentations (76.8%). Majority of
      the students (75.7%) expressed their willingness for a formal computer training
      programme at the faculty.Mean score for the computer literacy questionnaire was
      48.4 +/- 20.3, with no significant gender difference (Males-47.8 +/- 21.1,
      Females-48.9 +/- 19.6). There were 47.9% students that had a score less than 50%
      for the computer literacy questionnaire. Students from Colombo district, Western
      Province and Student owning a computer had a significantly higher mean score in
      comparison to other students (p < 0.001). In the linear regression analysis,
      formal computer training was the strongest predictor of computer literacy (beta =
      13.034), followed by using internet facility, being from Western province, using
      computers for Web browsing and computer programming, computer ownership and doing
      IT (Information Technology) as a subject in GCE (A/L) examination. CONCLUSION:
      Sri Lankan medical undergraduates had a low-intermediate level of computer
      literacy. There is a need to improve computer literacy, by increasing computer
      training in schools, or by introducing computer training in the initial stages of
      the undergraduate programme. These two options require improvement in
      infrastructure and other resources.

PMID- 22980097
TI  - Chemoinformatics: recent advances at the interfaces between computer and chemical
      information sciences, chemistry, and drug discovery.

PMID- 22980098
TI  - The effect of omega-3 fatty acids on psychophysiological assessment for the
      secondary prevention of posttraumatic stress disorder: an open-label pilot study.
AB  - Our recent pilot study has shown that the supplementation of omega-3 fatty acids
      (fish oil) immediately after a traumatic event may be effective toward the
      secondary prevention of post-traumatic disorder (PTSD). To lay the groundwork for
      addressing the mechanism by which omega-3 fatty acids can prevent PTSD, we
      analyzed its psychophysiological data. The psychophysiological data included
      heart rate, skin conductance, and continuous blood pressure during patient
      subjection to startling tones and idiographic trauma-related cues. Of the 8
      patients, 1 met the diagnostic criteria for PTSD. Compared to the seven patients
      without PTSD, one patient with PTSD showed relatively large reactivity to the
      startle tones. In contrast, this patient did not show large reactivity to the
      trauma-related cue during script-driven imagery. The combination of
      psychophysiological measurements in our randomized control trial should shed
      light on the underlying mechanisms by which omega-3 fatty acids can prevent PTSD.

PMID- 22980099
TI  - Understanding the antecedents of Korean high school students' drinking refusal
      self-efficacy: parental influence, peer influence, and behavior.
AB  - The current study examined the factors that influence Korean adolescents'
      drinking refusal self-efficacy, which is known to be associated with alcohol use
      and drinking intentions. Specifically, this study considered parental monitoring,
      parent-child communication satisfaction, peer influence, and prior alcohol use as
      possible antecedents of Korean high school students' drinking refusal self
      efficacy. High school students (n = 538) in South Korea responded to the current
      study. The data revealed that parent-child communication satisfaction facilitated
      parental monitoring, and these factors indirectly predicted adolescents' drinking
      behavior through peer influence. We also found that prior drinking, parental
      monitoring, and peer influence were directly associated with drinking refusal
      self-efficacy, and the self-efficacy, in turn, was associated with drinking
      intentions. These results not only suggest that drinking refusal self-efficacy
      are related to drinking behavior and intentions, but they also provide a
      theoretical explanation for how parental and peer influences are associated with
      adolescents' drinking refusal self-efficacy.

PMID- 22980100
TI  - Process evaluation of a psychosocial intervention addressing women in a
      disadvantaged setting.
AB  - OBJECTIVES: This paper presents the process evaluation of a community-based
      randomized psycho-social trial aimed to enhance reproductive and mental health
      outcomes of disadvantaged women living in the southern suburb of Beirut-Lebanon.
      Process evaluation of public health interventions involves the monitoring and
      documentation of interventions' implementation to allow for better understanding
      of planned outcomes and of intervention effectiveness. METHODS: A community-based
      randomized trial was conducted. The intervention consisted of 12 sessions (of
      combined 30 minutes of relaxation exercises and 75 minutes of structured support
      groups) delivered twice per week over a period of six-weeks. A process evaluation
      was conducted during the implementation of the intervention. This process
      evaluation aimed to ensure that the intervention was delivered and implemented as
      planned, as well as to monitor women's satisfaction and attendance. The main
      components of the process evaluation included: dose delivered, dose received, and
      reach. Closed ended questionnaires were administered before/after/during each
      intervention session. Data was entered and analyzed using SPSS. Analysis revolved
      around simple frequency distribution for categorical variables and means (SD) for
      continuous variables. Limited bivariate analysis (using CHI Square and Anova) was
      done. RESULTS: RESULTS indicated that the delivery, implementation, and reach of
      the intervention were favorable. Participation was acceptable and satisfaction
      rates were very high. CONCLUSION: These favorable findings pertaining to
      intervention satisfaction, reach and participation highlight a number of lessons
      for future intervention studies in the context of disadvantaged settings. They
      also support the importance of involving the local community members in
      intervention planning, implementation and evaluation early on. We believe that
      the community involvement in this trial directly and significantly contributed to
      the results of this process evaluation.

PMID- 22980101
TI  - Effect of an education program on improving help-seeking among parents of junior
      and senior high school students in Japan.
AB  - Early intervention in schizophrenia is important for patient prognosis and
      quality of life. At the time of the first episode, quality of life is influenced
      by identification of symptoms and by medical help-seeking behavior. In this
      prospective cohort study, we investigated help-seeking among 2690 parents of
      junior and senior high school students before and after the parents viewed a
      newly developed web-based education program aimed at improving knowledge of
      schizophrenia. Our web-based education program aimed to improve understanding of
      schizophrenia, including promotion of help-seeking. Many parents (33.1%-50.0%)
      consulted a physician in a department of psychosomatic medicine when their child
      experienced symptoms. Characteristics that predicted a decision not to seek
      psychiatric medical help were having child with all symptoms, younger parent age,
      and lower family income (p<0.05). After the education program, the rate of
      parents who sought medical help within 1 week was significantly higher for all
      symptom categories except sleeplessness (p=0.001). These findings suggest that
      the present web-based education program was useful in promoting medical help
      seeking behavior among parents of junior and senior high school students in
      Japan.

PMID- 22980102
TI  - Alcoholic beverages drinking among female students in a tourist province,
      Thailand.
AB  - This study aimed to investigate alcoholic beverages drinking and predictive
      factors among female students. The participants were 377 subjects from 3 high
      schools in a tourist province, of Thailand. Data collection was done through self
      administered questionnaire. Scales of the questionnaire had reliability
      coefficients ranging from 0.84 - 0.88. The data were analyzed by using
      descriptive and inferential statistics. The findings revealed as follows. About
      half (51%) of them have ever drunk and 10.5% of drinkers have drunk once a week.
      In addition, 15.6% of drinkers began their first drink when they were under 10
      years old. Risk factors for alcohol consumption of female student were age, GPA,
      drinker in family, peer pressure, advertisement and accessibility to alcoholic
      beverages while protective factors were perception of drinking impacts on family
      and moral values. Students who have a drinking family member were 4.6 times more
      likely to drink than those who do not have.

PMID- 22980103
TI  - Prevalence of neck pain and associated factors with personal characteristics,
      physical workloads and psychosocial among male rubber workers in FELDA settlement
      Malaysia.
AB  - Rubber tapping processes posed potential risk of various health problems among
      rubber workers. It ranges from simple musculoskeletal aches to more serious and
      complicated structural damage to bone, muscles, tendons and nerves of
      musculoskeletal system. These health problems might be linked directly to the
      arduous demands of farm labor. OBJECTIVES: A cross-sectional study was conducted
      to determine the prevalence of neck pain (NP) and musculoskeletal symptoms (MSS)
      and its association with personal characteristics, physical workloads and
      psychosocial factors among rubber workers. METHODS: Stratified random sampling
      method was adopted and a total of 419 rubber workers in FELDA's scheme Malaysia
      participated in this study. Data was collected through face to face interview
      using modified Standardized Nordic Questionnaire (SNQ) and Job Content
      Questionnaire (JCQ). RESULTS: The results revealed the prevalence of NP was 59.9%
      and weak correlation with age (?= -0.184, p= 0.001) and a positive weak
      correlation with working hours per day (?= 0.099, p= 0.043) significantly. All
      physical workloads (neck flexion or rotation, awkward postures, repetitive motion
      and static postures) had significant weak to moderate positive correlation with
      NP (p<0.05). Job insecurity was found to have weak and positive correlation with
      NP (p<0.05). Binary logistic regression analysis showed risk factors for NP were
      decreased with age (OR= 3.92, 95% CI 1.61 - 9.58, p=0.003), increase in neck
      flexion or rotation (OR= 9.52, 95% CI 5.55 - 16.32, p= 0.001), awkward postures
      (OR=2.23, 95% CI 1.29 - 3.86, p= 0.004) and static postures (OR= 1.86, 95% CI
      1.10 - 3.14, p= 0.021). CONCLUSION: This study showed that high prevalence of NP
      was associated with neck flexion or rotation, awkward and static postures.

PMID- 22980104
TI  - Effect of an integrated case-based nutrition curriculum on medical education at
      Qazvin University of Medical Sciences, Iran.
AB  - INTRODUCTION: Nutrition education is identified as an important part of medical
      education by organizations. Qazvin University of Medical Sciences, school of
      medicine (QUMS SOM), has a required basic nutrition course of 36 hr in second
      year of medical school, but education experts reports show that the course does
      not provide required therapeutic skills for graduate student. METHOD: We decided
      to organize an 8-hr diet therapy work shop in order to develop a patient
      experience clinical based case study teaching to enhance clinical skills at QUMS
      SOM. RESULTS: Students' perception score about adequacy of nutrition instruction
      increased from 20% (at baseline) to 70% (after intervention). The mean nutrition
      knowledge score of total students in clinical nutrition were different between
      before and one month after integration (8.3+/-2.5, 13.4+/-3.2, P < 0.001). And
      two groups of participants including staggers and interns had similar nutritional
      knowledge score at pre-test (7.9+/-2.6 and 8.9+/-2.3 respectively). CONCLUSION:
      Implemented nutrition curriculum at QUMS was appropriate method to enhance
      student's perception about nutrition integration and to increase and translate
      the knowledge to clinical practice.

PMID- 22980105
TI  - A case study and state of science review: private versus public healthcare
      financing.
AB  - Medicare is a popular program in Canada that offers universal access to medically
      necessary healthcare services for all Canadians through a public insurance plan
      in each province. In spite of its popularity, healthcare privatization has been
      debated, often over concerns about wait times for healthcare services. A case
      report focused on the 2005 Supreme Court's response to the "Chaoulli v. Quebec"
      challenge of the Quebec law banning the purchase of private health insurance for
      publicly-insured services is presented, along with findings from a state of
      science review to determine if there would be any benefit from adopting the
      United States model of private health insurance. This review reveals private
      health insurance would have significant negative implications, especially by
      creating inequity in healthcare access for low-income groups. Further study is
      needed to determine whether Canada's publicly-funded healthcare system would
      benefit in any way from increased private financing.

PMID- 22980106
TI  - Bio-activity of natural polymers from the genus Pistacia: a validated model for
      their antimicrobial action.
AB  - The polymers from mastic gum of Pistacia lentiscose and subspecies of Pistacia
      atlantica, (sp. kurdica, mutica and cabolica) have been isolated and
      characterised by gel permeation chromatography (GPC) and 13C NMR spectroscopy as
      cis-1,4-poly-?-myrcenes. They were screened against Helicobacter pylori and other
      Gram-negative and Gram-positive bacteria to evaluate their antimicrobial action.
      In order to further test their hypothesised mode of action, two polymer types
      were synthesized: one from myrcene, and four from polyvinyl alcohols of different
      molecular weights, derivatised with p-hydroxybenzoate. The anti-microbial
      activity of these polymers, evaluated through their 'kill' kinetics, was found to
      be related to their functional groups, their molecular weight and their
      solubility.

PMID- 22980107
TI  - Uses of 2-ethoxy-4(3H) quinazolinone in synthesis of quinazoline and
      quinazolinone derivatives of antimicrobial activity: the solvent effect.
AB  - 2- Ethoxy-4(3H) quinazolinone 1 was synthesized and allowed to react with various
      halides, namely: alkyl, benzyl, allyl, acyl, haloacetyl, crotonyl, benzoyl, 2
      furoyl and 1-naphthalenesulphonyl halides affording quinazoline and quinazolinone
      derivatives. The reactions of compound 1 with phosphorus oxychloride, phosphorus
      pentasulfide, ethyl chloroformate, ethyl chloroacetate, ?-bromoglucose
      tetraacetate, p-acylaminobenzenesulfonyl chloride, acrylonitrile, chalcone and
      chalcone oxide were also investigated. Depending on the reaction condition and
      reactant halide, the type of substituent (alkyl, acyl, aroyl, etc.) that will
      reside on either of the expected positions (3 or 4) on the quinazoline moiety can
      control the reaction pathway for synthesis of the promising products. The
      significant role of solvent responsible for determining both the reaction pathway
      and type of products synthesized was also discussed. Some derivatives were chosen
      for biological screening test against Gram (-ive) and Gram (+ive) bacteria and
      two strains of fungi.

PMID- 22980108
TI  - Reactivity of 2-ethoxyquinazolin- 4-yl hydrazine and its use in synthesis of
      novel quinazoline derivatives of antimicrobial activity.
AB  - The reactions of 2-ethoxy-4-hydrazinoquinazoline 2 with diethyl oxalate and ethyl
      chloroacetate gave 6-ethoxy-2H-[1,2,4]triazino[4,3-c]quinazoline-3,4-dione 3 and
      6-ethoxy-2,3-dihydro-4H-[1,2,4]triazino[4,3-c]quinazolin-4-one 4 respectively. A
      series of 5-ethoxy-2-X-[1,2,4]triazolo[1, 5-c]quinazolines 5a-d was also produced
      by reacting 2 with the acid chlorides namely: benzoyl, crotonyl, cinnamyl and 2
      furoyl chlorides via Dimroth rearrangement. Also, 2 reacted with ethyl
      chloroformate giving 6. Condensation of 2 with acetone gave Schiff base 7, and
      with monosaccharides gave the sugar hydrazones 8a-e which were thereafter
      acetylated giving the corresponding 9a-e. Cyclization of 8a-e by iron(III)
      chloride gave triazoloquinazolines 10a-e acyclic C-nucleosides which, by
      acetylation, afforded 11a-e. All products were confirmed by elemental, IR, MS,
      and 1H-NMR analysis. Products 8-11 were chosen for biological screening test
      against gram(+ ive) and gram(- ive) bacteria.

PMID- 22980109
TI  - Computed tomographic pattern of physiological intracranial calcifications in a
      city in central Africa.
AB  - OBJECTIVE: Intracranial calcifications underlie certain brain diseases which may
      be de novo or systemic. But calcifications un-connected to pathologies are
      classified physiological. AIM: To evaluate physiological intracranial
      calcifications in Douala with establishment of earliest age range of detection.
      MATERIALS AND METHODS: Prospective study of brain computed tomograms was done
      from April to October 2009 using Schumadzu CT Scan machine. Axial, reconstructed
      and bone window images as well Hounsfield unit measurements were used for final
      evaluations. RESULTS were analysed with SSPS 3. RESULTS: 132 patients with 75
      males and 57 females were studied and 163 separate calcifications were identified
      due to co-existent calcifications. The highest calcification was in choroid
      plexi, constituting 56.82% of the studied population. This was followed by pineal
      gland. Both were commonly co-existent with advancing age. These calcifications
      were first seen at 10-19 years. No type of physiological intracranial
      calcification was seen below age 10. The least calcification of 0.76% of
      population was in dentate nucleus. CONCLUSION: No intra-cranial physiological
      calcifications started earlier than 9 years in Douala, a city in Cameroon,
      Central Africa.

PMID- 22980110
TI  - The relationship between spatial patterns of illnesses and unemployment in Iraq
      2007.
AB  - Studies of the relationship between spatial patterns of chronic illnesses (CI)
      and unemployment rate (UR) characteristics were not well documented. However,
      when analyzing the data that were collected on geographic areas, the spatial
      effects were seldom considered. This study addresses this concern by applying the
      mapping and spatial analysis techniques in studying how UR pattern is related to
      the CI pattern in Iraq. The aim is to assess the existence of spatial pattern in
      CI across geographical areas, and find whether this pattern was influenced by the
      pattern of socioeconomic indicators such as UR. The study design was cross
      sectional census data obtained in 2007. Governorates were used as the respective
      units of the analysis. Two statistics of spatial autocorrelation based on sharing
      boundary neighbours known as global and local Moran measures were used to
      investigate the global and local clustering respectively. To investigate the
      bivariate spatial relationship between CI and UR, Wartenberg's (1985) measure was
      used. It was found that UR varied significantly across different governorates,
      while CI didn't. Significant local clusters in UR, in northern and southern parts
      of the country were found, while no significant local clusters were found in CI.
      No significant spatial association was found between CI and UR based on bivariate
      spatial correlation coefficient.

PMID- 22980111
TI  - 3-Self behavior modification programs base on the PROMISE Model for clients at
      metabolic risk.
AB  - The objectives of this mixed methods research were 1) to study effects of the
      health behavior modification program (HBMP) conducted under the principles of the
      PROMISE Model and the CIPP Model and 2) to compare the 3-self health behaviors
      and the biomedical indicators before with after the program completion. During
      the program, three sample groups including 30 program leaders, 30 commanders and
      120 clients were assessed, and there were assessments taken on 4,649 volunteers
      who were at risk of metabolic syndrome before and after the program conducted in
      17 hospitals. The collected data were analyzed by the t-test and the path
      analysis. The research instruments were questionnaires used for program
      evaluation, structuralized interview forms, and questionnaires used for 3-self
      health behavior assessment. The findings were as follows: 1) During the program,
      the assessment result deriving from comparing the overall opinions toward the
      program among the three sample groups showed no difference (F=2.219), 2) The
      program management factors based on the PROMISE Model (positive reinforcement,
      optimism, context, and process or activity provision) had an overall influence on
      the product or success of the HBMP (p< 0.05) with size effects at 0.37, 0.13,
      0.31 and 0.88 respectively. All of the factors could predict the product of the
      program by 69%. 3) After participating in the program, the clients' 3-self health
      behaviors (self-efficacy, self-regulation, and self-care) were significantly
      higher than those appeared before the participation (p< 0.05), and their
      biomedical indicators (BMI, blood pressure, waistline, blood glucose, lipid
      profiles, cholesterol, and HbA1c) were significantly lower than those measured
      before the program (p< 0.05).

PMID- 22980112
TI  - Effect of low glycemic load diet on glycated hemoglobin (HbA1c) in poorly
      controlled diabetes patients.
AB  - Different carbohydrate diets have been administrated to diabetic patients to
      evaluate the glycemic response, while Poor-controlled diabetes is increasing
      world wide. To investigate the role of an alternative carbohydrate diet on
      glycemic control, we explored the effect of a low glycemic load (Low GL)-high fat
      diet on glycemic response and also glycated hemoglobin (HbA1c) of poor-controlled
      diabetes patients. Hundred poorly-controlled diabetes patients, HbA1c > 8, age
      52.8 +/- 4.5 y, were administrated a low GL diet , GL = 67 (Energy 1800 kcal;
      total fat 36%; fat derived from olive oil and nuts 15%; carbohydrate 42%; protein
      22%) for 10 weeks. Patients did their routine life style program during
      intervention. Fasting blood glucose and HbA1c before and after intervention with
      significant reduction were: 169 +/- 17, 141 +/- 12; 8.85% (73 mmol/mol) +/-
      0.22%, and 7.81% (62 mmol/mol) +/- 0.27%; respectively (P < 0.001). Mean fasting
      blood glucose reduced by 28.1 +/- 12.5 and HbA1c by 1.1% (11 mmol/mol) +/- 0.3%
      (P=0.001). There was positive moderate correlation between HbA1c concentration
      before intervention and FBS reduction after intervention (P < 0.001, at 0.01
      level, R =0.52), and strong positive correlation between FBS before intervention
      and FBS reduction (P < 0.001, at 0.01 level, R = 0.70). This study demonstrated
      that our alternative low glycemic load diet can be effective in glycemic control.

PMID- 22980113
TI  - Isolation, analysis and antimicrobial activity of the acidic fractions of Mastic,
      Kurdica, Mutica and Cabolica gums from genus Pistacia.
AB  - The chemical entities of Mastic, Kurdica, Mutica and Cabolica gums from genus
      Pistacia have been isolated and characterised by GC-Mass Spectrometry, High
      Performance Liquid Chromatography and Column Chromatography. These chemical
      entities were screened for anti-microbial activities against nine strains of
      Helicobacter pylori and some other Gram-negative and Gram-positive bacteria. The
      most bioactive components were structurally analysed. These components mimic
      steroid compounds, in particular, the known antibiotic Fusidic acid.  Some of
      these chemical entities have produced promising data that could lead to the
      development of a novel class of antimicrobial agents that may have application in
      the treatment of infectious disease. Kill kinetics have been also performed, and
      the produced data were evaluated by Generalized Multiplicative Analysis Of
      Variance (GEMANOVA) for the bactericidal and bacteriostatic activities which can
      be clinically significant. The isolated components were all bactericidal.

PMID- 22980114
TI  - Effects of Dao De Xin Xi exercise on balance and quality of life in Thai elderly
      women.
AB  - The objective of this study was to evaluate the effects of a 12-week Dao De Xin
      Xi exercise, modified short forms of Tai Chi, on balance and quality of life in
      Thai elderly population. Quasi-Experimental research, pretest-posttest one group
      design was done at Physical Medicine and Rehabilitation Department,
      Phramongkutklao Hospital. Thai healthy elderly women over the age of 60,
      requiring regular Dao De Xin Xi exercise were recruited from either patients or
      workers in the hospital. A 60-minute Dao De Xin Xi exercise class was set as 3
      times per week for 12 weeks. At baseline and 12 weeks, participants were tested
      in their static balance (Single-Leg Stance Timed Test with eyes open and close),
      dynamic balance (Expanded Timed Up and Go (ETUG) Test). Quality of life was
      measured by the abbreviated Thai version of the World Health Organization Quality
      of Life (WHOQOL-BREF) questionnaire. Fourteen females were studied with mean age
      of 62.8+/-4.3 years old. The Single-Leg Stance Timed Test with eyes open and
      close, Expanded Timed Up and Go (ETUG) Test improved significantly (before versus
      after exercises p <0.001). Significant improvement in quality of life were also
      found in each 4 domains, including physical health, psychological, social
      relationship, and environment (before versus after exercises p =0.001, 0.001,
      0.004 and 0.005 respectively). No significant improvement was found only in the
      right Single-Leg Stance Timed Test with eyes close (p =0.091). A three times per
      week for 12-week Dao De Xin Xi exercise may help Thai elderly women improve both
      static, dynamic balance and quality of life.

PMID- 22980115
TI  - Intra-orbital malignant melanoma: role of MR imaging (a case report and
      literature review).
AB  - Magnetic resonance imaging is a non-invasive modern imaging tool that can
      definitely diagnose malignant melanoma despite its anatomic localisations. This
      is borne out of tumour paramagnetic melanin pigment content. Melanin is known to
      shorten T1 and T2 relaxation times of protons thereby exhibiting hyperintense T1W
      and hypointense T2W signals, hence conferring some histiological diagnosis. This
      is unlike Amelanotic melanoma, other intra-orbital tumours and tumours in general
      that show usual hypointense T1W and hyperintense T2W signals. However a few
      mimics of signal characteristics of malignant melanoma like sub-retinal serous
      collection exist. This therefore needs additional MRI sequences like fat
      suppression with Gado-pentetate Dimeglumine enhancement for differentiations.

PMID- 22980116
TI  - The influence of psycho-social factors on participation levels in community-based
      breast cancer prevention programs in Tehran, Iran.
AB  - BACKGROUND: Although significant consideration has been devoted to women
      participation in breast cancer prevention programs, our understanding about the
      psychosocial factors which influence participation remains incomplete. METHOD:
      The study applied a quantitative approach based on the cross-sectional survey
      design and multistage cluster random sampling. A total of 400 women aged 35-69
      years, were surveyed at 4 obstetric and gynecologic clinics affiliated to Tehran
      University of Medical Sciences in Tehran: the participation levels of 86 women
      who have had a mammogram were analyzed based on their self-efficacy, belief,
      social influence, and barriers concerning mammography utilization. RESULTS:
      Consistent with the study framework, in bivariate analysis, the higher level of
      women's participation in breast cancer prevention programs was significantly
      related to more positive belief about mammography (p< .05), greater social
      influence on mammography (p< .01) and fewer barriers to mammography (p< .01).
      Self efficacy (p= .114) was not significantly related to the higher level of
      participation. CONCLUSION: Results suggest that women's participation levels in
      breast cancer prevention programs might be associated with the specific
      psychosocial factors on breast cancer preventive behavior such as mammography
      screening.

PMID- 22980118
TI  - Age at menarche and menstrual cycle pattern among school adolescent girls in
      Central India.
AB  - BACKGROUND: The onset of menstruation is part of the maturation process. However,
      variability in menstrual cycle characteristics and menstrual disorders are
      common. The purpose of this study was to determine the age at menarche and
      patterns of menstruation among school adolescent girls and explore its variation
      across socio-economic and demographic factors. METHODOLOGY: This is a cross
      sectional descriptive study carried out on 1100 school adolescent girls in
      district Wardha, Central India. Data were collected using a self-administered
      structured questionnaire on menstruation. Data was entered and analyzed by using
      Epi Info 6.04 software package. Chi- square value was used for testing
      statistical significance. RESULTS: Mean ages of menarche were 13.51 + 1.04 years
      and 13.67 + 0.8 years for urban and rural areas respectively. Abnormal cycle
      length was common and affected 30.48%. The majority 56.15 experienced
      dysmenorrhoea and 56.16 percent had premenstrual syndrome. Self medication was
      practiced by 7.13% of the adolescent girls. The most common premenstrual symptom
      was headache 26.74%. Absenteeism from the school 13.9% was the effect of
      menstruation related problems on their daily routine. Dysmenorrhea and
      premenstrual symptoms were perceived as most distressing symptoms leading to
      school absenteeism. Majority of the girls 75.58% had discussed menstrual problems
      with someone, most commonly with their mothers 38.15%. There was a general lack
      of information about menstrual issues especially with regards to cycle length,
      duration of menses and age at menarche. Girls from families of high socio
      economic class have significantly lower mean menarcheal age in both urban and
      rural area. The mean age of menarche was significantly higher in girls involved
      in vigorous sporting activity in urban area compared to their non-sporting
      counterparts. CONCLUSION: Age at menarche was delayed. The menstrual disorders
      among female adolescents are common. A school health education on menstrual
      problems targeting adolescent girls and their parents and routine screening for
      menstrual problems by healthcare providers can help to prevent the absenteeism in
      the school.

PMID- 22980119
TI  - The impact of medical tourism on Thai private hospital management: informing
      hospital policy.
AB  - BACKGROUND: The purpose of this paper is to help consolidate and understand
      management perceptions and experiences of a targeted group (n=7) of Vice
      Presidents of international Private Thai hospitals in Bangkok regarding medical
      tourism impacts. METHODS: The method adopted uses a small-scale qualitative
      inquiry. Examines the on-going development and service management factors which
      contribute to the establishment and strengthening of relationships between
      international patients and hospital medical services provision. Develops a
      qualitative model that attempts to conceptualize the findings from a diverse
      range of management views into a framework of main (8) - Hospital Management;
      Hospital Processes; Hospital Technology; Quality Related; Communications;
      Personnel; Financial; and Patients; and consequent sub-themes (22). RESULTS:
      Outcomes from small-scale qualitative inquiries cannot by design be taken outside
      of its topical arena. This inevitably indicates that more research of this kind
      needs to be carried out to understand this field more effectively. The evidence
      suggests that Private Thai hospital management have established views about what
      constitutes the impact of medical tourism on hospital policies and practices when
      hospital staff interact with international patients. CONCLUSIONS: As the private
      health service sector in Thailand continues to grow, future research is needed to
      help hospitals provide appropriate service patterns and appropriate medical
      products/services that meet international patient needs and aspirations.
      Highlights the increasing importance of the international consumer in Thailand's
      health industry. This study provides insights of private health service providers
      in Bangkok by helping to understand more effectively health service quality
      environments, subsequent service provision, and the integrated development and
      impacts of new medical technology.

PMID- 22980120
TI  - Adhesive capabilities of Staphylococcus aureus and Pseudomonas aeruginosa
      isolated from tears of HIV/AIDS patients to soft contact lenses.
AB  - Fifty conjunctival swab samples collected from ELISA confirmed HIV/AIDS
      seropositive patients who were referred to the HIV/AIDS laboratories of the
      University of Benin Teaching Hospital and Central Hospital both based in Benin
      City, Nigeria were aseptically cultured on appropriate media by standard methods.
      The resulting isolates/strains, after identification by standard methods, were
      tested for their ability to adhere to two hydrophobic non-ionic daily wear
      silicone hydrogel soft contact lenses (i.e. lotrafilcon B, WC 33% and polymacon,
      WC 38%) as well as to two hydrophilic ionic conventional extended wear silicone
      hydrogel soft contact lenses (i.e. methafilcon A, WC 55% and omafilcon A, WC 60%)
      by the adhesiveness/slime production modified vortex/Robin device method.
      Evidence of adhesiveness/slime production was indicated by presence of a visible
      stained film lining the surface of the contact lens which was measured and
      recorded as strong or weak according to the density of the adhered bacterial
      film. Fourteen (28.0%) Staphylococcus aureus strains and 10 (20.0%) Pseudomonas
      aeruginosa strains were obtained among other organisms. Staphylococcus aureus
      strains adhered in decreasing order to lotrafilcon B (55.4 +/- 4.7), polymacon
      (46.4 +/- 8.4), methfilcon A (46.4 +/- 8.4) and omafilcon A (25.0 +/- 6.4) with
      no significant difference in adhesive strengths of individual strains (P > 0.05).
      Pseudomonas aeruginosa strains also recorded decreasing adhesive strengths to
      lotrafilcon B (37.5 +/- 8.2), polymacon (28.6 +/- 6.3), methafilcon A (26.8 +/-
      5.5) and omafilcon A (23.2 +/- 5.5) also with no significant difference in
      adhesive strengths of individual strains (P > 0.05). Attachment strengths of
      Staph. aureus strains to all four contact lenses were higher than those of
      Pseudomonas aeruginosa strains. Both organisms adhered most to hydrophobic
      lotrafilcon B and least to hydrophilic omafilcon A. This invitro adhesion studies
      revealed that daily wear silicone hydrogel low water content, non-ionic contact
      lenses are more prone to bacterial adhesion than the conventional extended wear
      hydrogel high water content, ionic contact lenses and hence, there is more risk
      of microbial adhesion to the former compared to the latter. Other implications
      are highlighted.

PMID- 22980117
TI  - Risks and complications of coronary angiography: a comprehensive review.
AB  - Coronary angiography and heart catheterization are invaluable tests for the
      detection and quantification of coronary artery disease, identification of
      valvular and other structural abnormalities, and measurement of hemodynamic
      parameters. The risks and complications associated with these procedures relate
      to the patient's concomitant conditions and to the skill and judgment of the
      operator. In this review, we examine in detail the major complications associated
      with invasive cardiac procedures and provide the reader with a comprehensive
      bibliography for advanced reading.

PMID- 22980121
TI  - Extrachromosomal DNA length and antibiograms of Staphylococcus aureus and
      Pseudomonas aeruginosa isolated from tears of HIV/AIDS patients after curing with
      sodium dodecyl sulphate.
AB  - Staphylococcus aureus and Pseudomonas aeruginosa strains were isolated from eye
      swab samples randomly obtained from 100 seropositive HIV/AIDS patients who
      reported to various anti-retroviral treatment clinics at the University of Benin
      Teaching Hospital and Central Hospital both based in Benin City, Nigeria. Invitro
      antibiotic sensitivity patterns of strains before curing were determined by the
      Kirby-Bauer disc diffusion technique. Resistance plasmid DNA of multidrug
      resistant strains was cured with 0.1% sodium dodecyl sulphate and cured strains
      were again subjected to in vitro antibiotic sensitivity testing. EcoRI and Hind
      III restriction endonuclease enzymes were used to make cuts on extracted plasmid
      DNA whose length sizes were then determined. A total of 36 (36.0%) strains made
      up of 27 (75.0%) Staphylococcus. aureus and 9 (25.0%) Pseudomonas aeruginosa were
      isolated of which 7 (19.4%) strains showed multidrug resistance to ciprofloxacin,
      pefloxacin, ofloxacine, gentamycin, tetracycline, ampicillin, chloramphenicol,
      nitrofurantoin and erythromycin. All seven multidrug resistant strains before
      curing, recorded 85.7%, 42.9%, 14.3% and 14.3% sensitivity in that decreasing
      order to ciprofloxacin, pefloxacin, ofloxacin and gentamycin respectively. There
      was 0.0% sensitivity each to tetracycline and ampicillin. After curing, there was
      enhanced sensitivity of 100.0%, 85.7%, 28.6% and 71.4% respectively. There was
      also 28.6% and 57.1% improved sensitivity to tetracycline and ampicillin after
      curing. Before curing, there was 76.2% average resistance to all used antibiotics
      and this reduced to 47.6% after curing Staph. aureus plasmid DNA. In the case of
      Pseudomonas aeruginosa, there was an average resistance of 76.3% before curing
      which fell to 42.5% after curing. EcoRI restriction enzyme gave the plasmid DNA
      length of Staphylococcus aureus strain 04 as 4.0Kb and this size depended upon
      the distance between recognition sites. Isolation of 36 (36.0%) strains of both
      isolates from 100 eye swabs shows the danger these organisms portend to all
      categories of opticians. The cheapness and high sensitivity of gentamycin
      justifies its use as eye drops for treatment of some eye infections. Curing of
      plasmid DNA is an indication that if SDS is administered to the organisms in
      sublethal doses, it can lead to the elimination of plasmid DNA without adverse
      effect on the genomic DNA of the bacterial strains.

PMID- 22980122
TI  - The effects of HIV/AIDS scourge on production and income among rural households
      in Adamawa State of Nigeria.
AB  - The paper investigates the determinants and the impact of HIV/AIDS on households
      in Adamawa State. 120 respondents affected with HIV/AIDS were selected for
      interview using simple random sampling techniques. Both primary and secondary
      data were used in its analysis to determine the impact of the disease on
      household's income. The data collected were analyzed using descriptive analytical
      techniques and a logistic regression model was employed to estimate the
      likelihood that a household witnessed a fall in income as a result of the
      disease. The paper revealed that HIV/AIDS had an adverse impact on household's
      productivity, income, saving and capital formation. The paper, therefore
      recommends an intensive Aids education programme and Government at all level as
      well as NGO's should endeavor to provide adequate HIV testing kits, medication
      and free counseling services to enable the households determine their HIV status.

PMID- 22980123
TI  - Conditional deletion of TrkC does not modify limbic epileptogenesis.
AB  - The neurotrophin receptor, tropomyosin-related kinase B (TrkB), is required for
      epileptogenesis in the kindling model. The role of a closely related neurotrophin
      receptor, TrkC, in limbic epileptogenesis is unknown. We examined limbic
      epileptogenesis in the kindling model in TrkC conditional null mice, using a
      strategy that previously established a critical role of TrkB. Despite elimination
      of TrkC mRNA, no differences in development of kindling were detected between
      TrkC conditional null and wild type control mice. These findings reinforce the
      central role of TrkB as the principal neurotrophin receptor involved in limbic
      epileptogenesis.

PMID- 22980124
TI  - Something's got to give: psychiatric disease on the rise and novel drug
      development on the decline.
AB  - Research and development of drugs for psychiatric disease is currently in a state
      of decline. Despite the increasing prevalence and healthcare costs of psychiatric
      disease, the costly and unpredictable drug development process has led to
      decreased public and investor confidence in the abilities of companies to develop
      safe and efficacious drugs. Industrial research in this disease area is therefore
      being scaled back owing to various scientific, corporate, financial and legal
      factors. This review will consider how these factors contribute to the current
      status of psychiatric drug development and offer several avenues forward to spur
      reinvestment in this type of research. Such a shift is needed to reduce the
      burden psychiatric disease imposes on the healthcare system and its patient
      populations.

PMID- 22980125
TI  - UV filters, ethylhexyl methoxycinnamate, octocrylene and ethylhexyl dimethyl PABA
      from untreated wastewater in sediment from eastern Mediterranean river transition
      and coastal zones.
AB  - UVF may occur in the aquatic environment through two principal sources: direct
      inputs from recreational activities and indirect wastewater- and river-borne
      inputs. The aim of this study was to obtain a first overview of levels of three
      UVF (EHMC, OC and OD-PABA) in coastal areas subjected to river inputs, untreated
      wastewater discharges and dumpsite leachates. We selected three eastern
      Mediterranean rivers that have been impacted for decades by untreated wastewater
      release and collected sediment in the coastal zone during the hot and humid
      seasons. Western Mediterranean sites receiving treated wastewaters were analyzed
      for comparison. The results gave an overview of sediment contamination under
      these two contrasted situations representative of Mediterranean coastal areas
      without bathing activities. The analysis of the three UVF revealed the ubiquity
      and high point source contamination by EHMC and OC in transition and coastal
      zones, with levels as high as 128 ng g(-1)d.w. OD-PABA was also frequently
      detected, but at lower concentrations (<LOD-17 ng g(-1)d.w.). A temporal trend
      was observed, with a higher sediment concentration in the dry period (August and
      October). Based on these results, we conclude that there is background
      contamination from river input that could be exacerbated by the direct
      contribution in coastal bathing zones.

PMID- 22980126
TI  - Assessing confinement in coastal lagoons.
AB  - Measures of transport scale in aquatic systems can contribute to the formulation
      of definitions of indicators of the system's ecological properties. This paper
      addresses confinement, a specific transport scale proposed by biological
      scientists as a parameter that can capture and synthesize the principal
      properties that determine the spatial structure of biological communities in
      transitional environments. Currently, there is no direct experimental measure of
      confinement. In this study, a methodology based on the accumulation rate within a
      lagoon of a passive tracer of marine origin is proposed, the influences of
      different factors in the calculation of confinement are analyzed, and general
      recommendations are derived. In particular, we analyze the spatial and the
      temporal variability of confinement and its sensitivity to the seasonal
      variability of climatic forcing, the inputs from rivers and the parameterization
      of the tidal exchanges. The Lagoon of Venice is used as a case study.

PMID- 22980127
TI  - Ischemia modified albumin levels cannot predict stress induced ischemia shown by
      myocardial perfusion scintigraphy.
AB  - PURPOSE: Ischemia modified albumin (IMA) is a new marker of ischemia which is
      used in especially emergency room. Aim of this study is showing the association
      of IMA with stress induced ischemia on Tc-99m 2-methoxyisobutyl-nitrate (MIBI)
      myocardial perfusion scintigraphy (MPS). METHODS: 56 patients (23 F, 33 M; 56.04
      +/- 8.45 years old) were included in our study. Stress-rest two days protocol Tc
      99m MIBI MPS single photon emission tomography (SPECT) was performed to all
      patients. IMA levels from the blood samples which were taken before and after the
      treadmill test were measured. Thirty patients additionally underwent coronary
      angiography. RESULTS: The difference of IMA levels of ischemia between positive
      and negative groups was not statistically significant. Also, there was not
      statistically significant difference between IMA levels of patients who have
      narrowing in the coronary arteries and not. CONCLUSION: Although IMA is an
      important marker of ischemia, probably because of other ischemic process during
      stress; it cannot reflect stress induced ischemic changes on MPS.

PMID- 22980128
TI  - Unusual presentation of sarcoid-like reaction on bone marrow level associated
      with mediastinal lymphadenopathy on (18)F-FDG-PET/CT resembling an early
      recurrence of Hodgkin's Lymphoma.
AB  - (18)F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive
      results are quite frequent, generally due to active phase of inflammation. We
      describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a
      patient monitored for Hodgkin Lymphoma characterized by an intense uptake in
      lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was
      obtained by biopsy. This study draws attention to the fact that multifocal bone
      marrow uptakes due to a sarcoideal reaction may be a possible cause of false
      positive results in (18)F-FDG-PET/CT studies in oncology patients.

PMID- 22980129
TI  - Normal blood glucose level and (18)F-FDG PET/CT.
AB  - Patient preparation for FDG PET studies is perhaps more critical and more complex
      than for any other commonly performed imaging procedure. We report a patient with
      normal blood glucose level prior to the execution of a PET study in which FDG
      uptake was virtually zero in internal organs and was very extense in large muscle
      groups. The patient recognizes ingestion several minutes before the test. Ten
      days later, a repeated PET scan with normal blood glucose level, showed a normal
      organs distribution of FDG.

PMID- 22980130
TI  - The role of brain perfusion SPECT in Moyamoya disease.
AB  - Moyamoya disease (MMD) is a cerebrovascular disorder involving stenosis of brain
      vessels. Brain perfusion SPECT in MMD demonstrates impaired perfusion in ischemic
      areas. We present a 6-year-old boy with MMD. The patient had numbness on the
      right arm and simultaneous electroencephalography changes while studying arms up
      on the table. To differentiate seizure and ischemic symptoms, brain perfusion
      SPECT studies were obtained when the patient was asymptomatic (SPECT-A) and
      during the symptoms-EEG changes (SPECT-B). SPECT-A showed perfusion defect on the
      right frontal cortex, hypoperfusion on the right parieto-occipital region and
      slightly increased perfusion on the left parietal cortex. SPECT-B displayed
      significant hyperperfusion on the left parietal cortex; hypoperfusion on the
      right parietal, right temporal, right parieto-occipital and left frontal cortex.
      Additionally, brain perfusion SPECT of the child's younger brother diagnosed with
      MMD showed decreased regional cerebral perfusion. Physiopathological mechanisms
      of our patient's SPECT findings and indications of brain perfusion SPECT in MMD
      were also discussed.

PMID- 22980131
TI  - [Occult papillary thyroid carcinoma in thyroglossal cyst diagnosed by (18)FDG
      PET/CT scan].

PMID- 22980132
TI  - Multimodality imaging in biochemical recurrence of prostate cancer: utility of
      (18)F-NaF PET/CT in early detection of metastasis.

PMID- 22980133
TI  - Diagnosis and assessment of the treatment response in a case of giant cell
      arteritis using (18)F-FDG PET/CT.

PMID- 22980134
TI  - Diagnosis of pulmonary adenocarcinoma due to hip bone metastasis.

PMID- 22980136
TI  - Degree of agreement between impulse and magnitude of momentum change for
      different types of movements.
AB  - This study aims to investigate the degree of agreement between the impulse and
      the magnitude of momentum change (MMC) for various types of movements. Six males
      performed five successful trials for four movements: straight jogging (SJo), 90
      degrees  open cross cutting (OC), running jump for height (RJu), and curved
      jogging with a 5-m radius (CJo). Impulse and MMC were respectively measured using
      two forceplates and a 3D motion capture system with 10 infrared cameras.
      Correlation coefficients between the two were over 0.95 except for RJu's medio
      lateral component (0.83). RJu motion is mainly in the sagittal plane, and it has
      a high-frequency impact force at touchdown; the accompanying noise explains the
      low correlation. In the vertical component, MMC increased with the impulse value.
      However, the relative error was ~10%. This is attributable to random equipment
      errors, error amplifications due to numerical calculations, and skin movements.

PMID- 22980137
TI  - Factors predicting weight-bearing asymmetry 1month after unilateral total knee
      arthroplasty: a cross-sectional study.
AB  - Factors predicting weight-bearing asymmetry (WBA) after unilateral total knee
      arthroplasty (TKA) are not known. However, identifying modifiable and non
      modifiable predictors of WBA is needed to optimize rehabilitation, especially
      since WBA is negatively correlated to poor functional performance. The purpose of
      this study was to identify factors predictive of WBA during sit-stand transitions
      for people 1month following unilateral TKA. METHODS: Fifty-nine people were
      tested preoperatively and 1month following unilateral TKA for WBA using average
      vertical ground reaction force under each foot during the Five Times Sit-to-Stand
      Test. Candidate variables tested in the regression analysis represented physical
      impairments (strength, muscle activation, pain, and motion), demographics,
      anthropometrics, and movement compensations. RESULTS: WBA, measured as the ratio
      of surgical/non-surgical limb vertical ground reaction force, was 0.69 (0.18)
      (mean (SD)) 1month after TKA. Regression analysis identified preoperative WBA
      (beta=0.40), quadriceps strength ratio (beta=0.31), and hamstrings strength ratio
      (beta=0.19) as factors predictive of WBA 1month after TKA (R(2)=0.30).
      CONCLUSION: Greater amounts of WBA 1month after TKA are predicted by modifiable
      factors including habitual movement pattern and asymmetry in quadriceps and
      hamstrings strength.

PMID- 22980138
TI  - Darbepoetin alfa administration in patients with non-Hodgkin lymphoma and
      chemotherapy-induced anemia receiving (+/-R) CHOP.
AB  - IMPACT NHL was a multicenter, observational study in adults with non-Hodgkin
      lymphoma receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisolone) chemotherapy with or without rituximab. Erythropoietin-stimulating
      agent treatment was given according to routine clinical  practice and physician
      preference. In a subanalysis, outcomes were evaluated in 207 patients who
      received darbepoetin alfa (DA). The most common reason (81%) for initiating DA
      was low/declining hemoglobin (Hb) concentration. Mean (+/-standard deviation)
      duration of DA exposure was 8.8 +/- 6.9  weeks (mean number of doses, 5.1 +/-
      4.6). Overall, 23% of patients had chemotherapy and DA treatment synchronized
      more than 75% of the time. At the time of DA initiation, 67% of patients had Hb
      concentrations in the guideline-recommended range (9-11 g/dl). Of 89  patients
      with Hb concentrations <10 g/dl at DA initiation and still receiving DA 5 weeks
      later, 92% (Kaplan-Meier) achieved Hb concentrations 10-12 g/dl between week 5
      and at the end of treatment.

PMID- 22980139
TI  - Mitochondrial fission and fusion in Dictyostelium discoideum: a search for
      proteins involved in membrane dynamics.
AB  - BACKGROUND: Mitochondrial morphology is maintained by two distinct membrane
      events -fission and fusion. Altering these conserved processes can disrupt
      mitochondrial morphology and distribution, thereby disrupting the organelle's
      functionality and impeding cellular function. In higher eukaryotes, these
      processes are mediated by a family of dynamin-related proteins (DRP's). In the
      lower eukaryotes, for instance Dictyostelium discoideum, mitochondrial fission
      and fusion have been implicated but not yet established. To understand the
      overall mechanism of these dynamics across organisms, we developed an assay to
      identify fission and fusion events in Dictyostelium and to assess the involvement
      of the mitochondrial proteins, MidA, CluA, and two DRP's, DymA and DymB.
      FINDINGS: Using laser scanning confocal microscopy we show, for the first time,
      that lower eukaryotes mediate mitochondrial fission and fusion. In Dictyostelium,
      these processes are balanced, occurring approximately 1 event/minute.
      Quantification of the rates in midA-, cluA-, dymA-, or dymB- strains established
      that MidA appears to play an indirect role in the regulation of fission and
      fusion, while the DRP's are not essential for these processes. Rates of fission
      and fusion were significantly reduced in cluA-cells, indicating that CluA is
      necessary for maintaining both fission and fusion. CONCLUSIONS: We have
      successfully demonstrated that Dictyostelium mitochondria undergo the dynamic
      processes of fission and fusion. The classical mediators of membrane dynamics -
      the DRP's - are not necessary for these dynamics, whereas CluA is necessary for
      both processes. This work contributes to our overall understanding of
      mitochondrial dynamics and ultimately will provide additional insight into
      mitochondrial disease.

PMID- 22980140
TI  - Indicators for acute hypoxia--an immunohistochemical investigation in cerebellar
      Purkinje-cells.
AB  - The Purkinje-cells (PCs) of the cerebellum are highly vulnerable to
      hypoxic/ischemic insult. Calbindin-D28k is a calcium-binding protein that is
      strongly expressed in PCs. Following hypoxia, a decrease in its concentration has
      been found in animal models before any morphological change of the PCs took
      place. Hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial
      growth factor (VEGF) are increasingly expressed in tissues that undergo durations
      of hypoxia, and also in brain tissues. We examine whether a change in expression
      of any of these factors, or a combination of alterations, is an indicator of
      acute hypoxia. We investigated the intensity of neuronal immunoreactivity of
      calbindin-D28k, HIF-1alpha and VEGF retrospectively in 141 samples of human
      cerebellar tissue obtained from autopsies performed at the Institute of Legal
      Medicine of Hanover Medical School in 2007 and 2008. Three groups were compared.
      The first group comprises individuals (n=48) who died due to acute hypoxia, such
      as drowning or asphyxia. The second is a control group comprising individuals who
      died due to heart failure (n=56), and the third group comprised individuals who
      died almost instantly of polytraumata (n=37). Our study finds a statistically
      significant decrease in the expression of calbindin-D28k (p<0.05) in PCs in the
      acute hypoxia group, relative to the control groups. No changes in the expression
      of HIF-1alpha or in the expression of VEGF were observed in any of the groups.
      Consequently HIF-1alpha and VEGF were not suitable indicators, whereas detection
      of a decreasing concentration of calbindin-D28k supports a diagnosis of acute
      hypoxia.

PMID- 22980141
TI  - Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink
      discolouration and chemical-analytical interferences.
AB  - Here we report the case of a 70-year-old woman who committed suicide by cyanide
      poisoning. During resuscitation cares, she underwent an antidote treatment by
      hydroxocobalamin. Postmortem investigations showed marked bright pink
      discolouration of organs and fluids, and a lethal cyanide blood concentration of
      43 mg/L was detected by toxicological investigation. Discolouration of hypostasis
      and organs has widely been studied in forensic literature. In our case, we
      interpreted the unusual pink coloration as the result of the presence of
      hydroxocobalamin. This substance is a known antidote against cyanide poisoning,
      indicated because of its efficiency and poor adverse effects. However, its main
      drawback is to interfere with measurements of many routine biochemical
      parameters. We have tested the potential influence of this molecule in some
      routine postmortem investigations. The results are discussed.

PMID- 22980142
TI  - Person identification in Ethnic Indian Goans using ear biometrics and neural
      networks.
AB  - This study presents new insights and experimental results for the use of ears as
      a non-invasive biometric for human identification. To determine the uniqueness of
      the external ear pattern two methods were employed: The Weighted Scoring System
      and Pattern Recognition by Neural Networks. A total of 10 external ear features
      classified into 37 sub-features for both right and left ears of 400 Indians of
      Goan origin were studied after acquiring standardized side profile digital
      photographs. These features were then converted to numeric scores by the
      'Weighted Scoring System' which were then compared to ascertain the uniqueness of
      ear pattern in same and different individuals. Apart from this feature-wise
      comparison, the initially acquired photographs of 800 individual ears were
      scrutinized and 80 visually similar ear patterns were found. After appropriate
      pre-processing of five train and five test images of each of these 80 visually
      similar ear patterns, the images were analyzed by a specially designed software
      and 360 feature vectors which were the distances from the centroid to the outer
      edge of the ear were extracted and saved. The feature vectors of train and test
      images were employed to train and test the Neural Networks. The result revealed
      that none of the individuals in the study sample had identical weighted scores
      when both right and left ear scores were considered in combination or when
      bilateral comparison was made in the same individual. The digital analysis of
      visually similar ear images by Neural Networks revealed a recognition rate of 94%
      with an Equal Error Rate at threshold value of 0.225. The inter-individual match
      score among train images were found to be less than the intra-individual match
      scores between train and test images or the differences found in former were more
      than that in the latter. Also, all intra-individual scores were above the system
      threshold (0.225) hence accepted as match, while all inter-individual scores were
      below it and hence rejected as a match. An independent t-test applied to the
      intra- and inter-individual match scores indicated that the two distributions
      were significantly different (p<0.0001). Thus, this study has been successful in
      determining the uniqueness of ear pattern for person identification and in
      designing and testing software for recognition of ear patterns from side profile
      photographs.

PMID- 22980143
TI  - Distribution of free and conjugated cannabinoids in human bile samples.
AB  - The metabolism of Delta(9)-tetrahydrocannabinol (THC) is relatively complex, and
      over 80 metabolites have been identified. However, much less is known about the
      formation and fate of cannabinoid conjugates. Bile excretion is known to be an
      important route for the elimination of phase II metabolites. A liquid
      chromatography-tandem mass spectrometry LC-MS/MS procedure for measuring
      cannabinoids in oral fluid was adapted, validated and applied to 10 bile samples.
      THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy
      Delta(9)-tetrahydrocannabinol (THCCOOH), cannabinol (CBN), cannabidiol (CBD),
      Delta(9)-tetrahydrocannabinolic acid A (THC-A), 11-nor-9-carboxy-Delta(9)
      tetrahydrocannabinol glucuronide (THCCOOH-gluc) and Delta(9)-tetrahydrocannabinol
      glucuronide (THC-gluc) were determined following solid-phase extraction and LC
      MS/MS. High concentrations of THCCOOH-gluc were found in bile samples (range: 139
      21,275 ng/mL). Relatively high levels of THCCOOH (7.7-1548 ng/mL) and THC-gluc
      (38-1366 ng/mL) were also measured. THC-A, the plant precursor of THC, was the
      only cannabinoid that was not detected. These results show that biliary excretion
      is an important route of elimination for cannabinoids conjugates and that their
      enterohepatic recirculation is a significant factor to consider when analyzing
      blood elimination profiles of cannabinoids. Furthermore, we suggest that the bile
      is the matrix of choice for the screening of phase II cannabinoid metabolites.

PMID- 22980144
TI  - Reported assaults and observed injuries in detainees held in police custody.
AB  - The deprivation of liberty in police custody can be associated with violent
      situations and traumatic injuries. The rare available data did not mention
      whether alleged assaults occurred at the time of the arrest or during custody.
      Our objectives were to describe the frequency of recent traumatic injuries
      observed in detainees at the time of medical examination and to record detainees'
      self-reports of received physical violence, either before being arrested, at the
      time of the arrest, or during custody. In 2694 consecutive detainees examined in
      a suburban area near Paris, we compared persons' characteristics in four groups,
      according to the existence of alleged assaults or the presence of recent
      traumatic injuries, or both. Detainees reported to be victims of physical
      assaults in 25% of cases (686 of 2694): 374 assaults of 686 (55%) occurred at the
      time of arrest and 87 of 686 (13%) during custody. The opinion of assaulted
      detainees on custody was worse than non-assaulted detainees. Detainees alleging
      assaults by the police, whatever the time of the assault, accounted for 396 cases
      (15%). Three quarters of detainees (547 of 686, 79%) alleging assaults had recent
      traumatic injuries. When we considered all detainees, medical examination showed
      recent traumatic injuries in 724 of 2694 (27%). Injured detainees were declared
      unfit for detention more frequently than non-injured non-assaulted detainees
      (P<0.05). These results strengthen the need and usefulness that the attending
      physician systematically takes note of detainees' self reports of assaults and
      investigates recent traumatic injuries at the time of custody.

PMID- 22980145
TI  - Spectroscopic techniques for quantitative characterization of Cu (II) and Hg (II)
      complexation by dissolved organic matter from lake sediment in arid and semi-arid
      region.
AB  - Dissolved organic matter (DOM) was extracted from six sediment samples in arid
      and semi-arid region, which was characterized by fluorescence excitation-emission
      matrices (EEMs). The results showed that four fluorescent peak, fulvic-like (peak
      A), humic-like (peak C) and two tryptophan-like (peaks B and D), were identified
      in lake sediment DOM. Fluorescence quenching titration showed that peaks B and D
      were quenched gradually by adding additional Cu (II) and Hg (II), whereas humic
      like substances had no systematic trend of the change of fluorescence intensity.
      Increasing fluorescence intensity value of humic-like substances can also be
      found. The modified Stern-Volmer model was used to calculate conditional
      stability constants (logK) and the percent of fluorophores (f %) which
      participate in the complexation between DOM and Cu (II), and Hg (II). The results
      showed that DOM-Cu (II) and DOM-Hg (II) complexes had higher logK values of 4.21
      5.23 and the logK values of DOM-Cu (II) are much larger than the corresponding
      values for Hg (II). Peak B showed relatively low logK and high f % values than
      those of peak D. Different pollution sources which are mainly obtained from the
      upstream industrial wastewater, domestic sewage and return water of farmland
      irrigation tend to affect the stability constants and complexing capacities of Cu
      (II) and Hg (II).

PMID- 22980146
TI  - AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with
      haloperidol efficacy during acute treatment.
AB  - We previously investigated a sample of psychotic patients acutely ill and acutely
      treated with haloperidol in the search for genetic predictors of response at
      PANSS scores during the first month of treatment. In the present work we extend
      the analysis to a wider panel of genetic variations including SNPs harbored by
      genes whose products are involved in molecular pathways consistent with the
      latest results of genome-wide association studies (GWAS) of antipsychotic
      efficacy. 96 Patients were investigated. The results were replicated in an
      independent sample of bipolar manic patients treated with antipsychotics (n
      tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS
      variation through time in the first sample, and changes of mania symptomatology
      at any two consecutive observations in the public available STEP-BD replication
      sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were
      found to be significantly associated with outcome in both samples (different set
      of variations for each sample). Results did not survived multiple testing in the
      original sample but were replicated in both samples. This finding stresses the
      relevance of the glutamatergic system and regulatory molecular cascades in
      antipsychotic response. Nonetheless, the level of significance and the indirect
      and incomplete replication mandate cautiousness and further replication. 

PMID- 22980147
TI  - Design principles to accommodate older adults.
AB  - The global population is aging. In many industrial countries, almost one in five
      people are over age 65. As people age, gradual changes ensue in vision, hearing,
      balance, coordination, and memory. Products, communication materials, and the
      physical environment must be thoughtfully designed to meet the needs of people of
      all ages. This article summarizes normal changes in sensory function, mobility,
      balance, memory, and attention that occur with age. It presents practical
      guidelines that allow design professionals to accommodate these changes and
      better meet the needs of older adults. Designing for older adults is inclusive
      design: it accommodates a range of physical and cognitive abilities and promotes
      simplicity, flexibility, and ease of use for people of any age.

PMID- 22980148
TI  - How can peer group influence the behavior of adolescents: explanatory model.
AB  - The current work aims to study both the peer group and family influence on
      adolescent behaviour. In order to achieve the aforementioned objective, an
      explanatory model based on the Structural Equations Modelling (SEM) was proposed.
      The sample used was the group of adolescents that participated in the Portuguese
      survey of the European study Health Behaviour in School-aged Children (HBSC). The
      Portuguese survey included students from grades 6, 8 and 10 within the public
      education system, with an average age of 14 years old (SD=1.89). The total sample
      of the HBSC study carried out in 2006 was 4,877; however with the use of the SEM,
      1,238 participants were lost out of the total sample. The results show that peers
      have a direct influence in adolescents' risk behaviours. The relationship with
      parents did not demonstrate the expected mediation effect, with the exception of
      the following elements: relation between type of friends and risk behaviour; and
      communication with parent and lesser involvement in violence behaviours and
      increased well-being. The negative influence of the peer group is more connected
      to the involvement in risk behaviours, whilst the positive influence is more
      connected with protective behaviours.

PMID- 22980149
TI  - Validity and reliability of an estimated daily intake scale for fat.
AB  - The reliability and validity of an Estimated Daily Intake Scale for Fat (EDIS-F)
      used to measure daily intake of fat in a participant's diet was tested. A
      Cronbach's alpha was used to determine the reliability of the EDIS-F. To
      determine the validity of this scale, scores on this scale were correlated with
      known factors related to daily intake of fat (e.g., ratings of liking for a high
      fat food and the body mass index score of participants). A 13-item EDIS-F was
      shown to be reliable, and scores on the EDIS-F significantly correlated with
      ratings of liking for a high fat cream cheese cracker and BMI, but not with
      gender, consistent with the assertion that this scale measures daily intake of
      fat. Implications for using this scale are discussed.

PMID- 22980150
TI  - Association between periodontal disease and peptic ulcers among Japanese workers:
      MY health up study.
AB  - OBJECTIVE: This study aimed to investigate the association between periodontal
      disease and peptic ulcers in a working population. METHODS: Self-administered
      questionnaires were distributed to all employees of a large insurance company in
      Japan. The questionnaire asked about their health status and lifestyle habits.
      Peptic ulcer was defined as either stomach ulcer, duodenal ulcer, or both. For
      the evaluation of periodontal disease, three indices were used: (a) loss of five
      or more teeth, (b) having been told of having periodontitis, and (c) periodontal
      risk score. RESULTS: Of the eligible 28 765 subjects analyzed, peptic ulcer was
      present in 397 (1.4%). The results of bivariate analyses showed that a
      significantly higher proportion of subjects with peptic ulcer reported that they
      lost five or more teeth (35.3 vs. 17.4%, p<0.001) or that they were told they had
      periodontitis (33.5 vs. 20.7%, p<0.001). Moreover, the periodontal risk score was
      higher for those with peptic ulcer than those without (mean 0.83 vs. 0.59,
      p<0.001). In multivariate logistic regression analyses, statistical associations
      were found between the presence of peptic ulcer and loss of five or more teeth
      (odds ratio (OR): 1.41, 95% confidence interval (CI): 1.13-1.76, p<0.01), having
      been told of having periodontitis (OR: 1.28, 95% CI: 1.03-1.59, p<0.05), and a 1
      point increase in the periodontal risk score (OR: 1.17, 95% CI: 1.04-1.30,
      p<0.01), respectively. CONCLUSION: Modest but statistically significant
      associations were found between the self-reported measures of periodontal disease
      and peptic ulcers.

PMID- 22980151
TI  - Clinical pathways as instruments for risk and cost management in hospitals - a
      discussion paper.
AB  - INTRODUCTION: The distinctive characteristics of the German health system are
      medical progress and financial pressure-and this is especially true of the
      hospitals. These challenges must be met by strategic management instruments for
      quality assurance, and by reducing costs. PURPOSE: This article presents the
      instrument "clinical pathway" (also known as "clinical treatment pathway") and
      describes the possibilities it offers, both for quality assurance and risk
      management, and for cost reduction. The clinical pathway presented here will be
      that for "multimodal pain therapy", as used in the context of acute inpatient
      care in Germany. METHODS: A general presentation of the risks in hospital is
      followed by consideration of the risks associated with core processes. A
      comprehensive total cost analysis is performed for those patients who meet the
      pathway entry criteria and who fulfil the requirements for the structure of care
      provided within multimodal pain therapy. DISCUSSION AND CONCLUSION: Multimodal
      pain therapy places high demands on the structural, procedural and outcome
      quality of the medical, nursing and therapeutic services provided, and these
      demands are reflected in high costs for the provision of this care. The treatment
      process involves many different professional groups. These complex interfaces can
      potentially generate risks, which can lead to the possibility of legal liability.
      A clinical pathway must structure the core process and then combine elements of
      quality assurance in order to optimise patient care and minimise risk. The
      examination of costs reveals significant potential savings (patients with
      clinical pathway: EUR 3086+/-212; patients without clinical pathway: EUR 3774+/
      460; Mann-Whitney U test; p<0.001). For the managers of a hospital, the clinical
      pathway represents a strategic management instrument that can serve for continual
      cost control and cost reduction, and can contribute in the form of quality
      assurance towards a transparent provision of services.

PMID- 22980152
TI  - Determinants of male partner involvement in promoting deliveries by skilled
      attendants in Busia, Kenya.
AB  - A cross-sectional study covering 380 male partners and their spouses was
      conducted in Busia district in Western Kenya to establish demographic, socio
      economic and cultural factors that affect male partner participation in promoting
      deliveries by skilled attendants. The study showed a significant relationship
      between level of education (P=0.0000) and level of income (P=0.0004) of the male
      partner and his support for skilled delivery. Lack of knowledge by male partners
      of complications associated with delivery, cultural beliefs, high fees charged
      for deliveries at health facilities and "un-cooperative" health workers are major
      contributing factors to low male partner involvement in child birth activities.
      Improving the levels of education and income of male partners, addressing the
      cultural beliefs and practices, improving health care provider-client
      relationship and sensitizing men on complications associated with pregnancy and
      child birth can contribute significantly in enhancing male partner involvement in
      promoting deliveries by skilled attendants.

PMID- 22980153
TI  - Knowledge and use of zinc supplementation in the management of childhood
      diarrhoea among health care workers in public primary health facilities in Benin
      City, Nigeria.
AB  - INTRODUCTION: Zinc supplementation reduces the severity, duration and recurrence
      of childhood acute diarrhoea. These beneficial effects of zinc in the treatment
      of diarrhoea led to the inclusion of a 10-14 days treatment regimen by the
      WHO/UNICEF. This study assessed the level of knowledge and use of zinc
      supplementation in the management of childhood diarrhoea among health care
      workers in public primary health facilities in Benin-City, Nigeria. METHODOLOGY:
      This cross-sectional study was carried out among the total population of health
      care providers in public primary health facilities in Benin-City. Data collection
      was done using a pre-tested, structured, self-administered questionnaire and data
      was analyzed using SPSS version 15.0. RESULTS: A total of 168 health care workers
      participated in the study. Two-thirds of them were aware of zinc supplementation
      but specific knowledge of zinc supplementation in the management of childhood
      acute diarrhoea was poor. Thirty-five percent of them prescribed zinc when
      managing childhood diarrhoea and only 10% of these do so for every case of
      childhood diarrhoea. About 84.6% of them prescribed the correct dose of zinc
      while less than half of them prescribe it for the correct duration. All but one
      of them prescribed zinc in addition to ORS in line with the WHO guideline.
      DISCUSSION: The study revealed a gap in the knowledge and practice of use of zinc
      supplementation in the management of childhood diarrhoea. It is recommended that
      nationwide campaigns should be embarked on to promote the use of zinc
      supplementation in the clinical management of childhood diarrhoea.

PMID- 22980154
TI  - Educating youths to make safer choices: results of a program evaluation study.
AB  - Injuries are a leading cause of childhood death and disability. Many injuries are
      a result of youths taking risks and not avoiding risky situations. An educational
      program to reduce adolescent injury risk (Prevent Alcohol and Risk-Related Trauma
      in Youth) has operated out of the Misericordia Hospital in Edmonton Canada since
      1992. This reality-based program was evaluated to see if it was impacting program
      participants. An increase in correct answers for some knowledge, behavior, and
      attitude questions were found at one week and one month following this 1-day
      reality-based program. This program was thus considered as having some relevancy
      in educating grade-9 youths. Although a longitudinal study is needed to determine
      if this relevancy is long term, this study highlights the importance of reality
      based public health programs.

PMID- 22980155
TI  - Weight bearing asymmetry and functional ambulation performance in stroke
      survivors.
AB  - This study evaluated asymmetry of weight bearing on the lower limbs and the
      association between percentage weight bearing asymmetry (PWBA) and functional
      ambulation performance in ambulant stroke survivors. Participants were 53 stroke
      survivors (male = 35, female = 18) aged 40-86 years (mean=58.87; SD=9.21years)
      with hemiparesis. Weight bearing through the lower limbs in standing was assessed
      by two juxtaposed bathroom weighing scales while functional ambulation
      performance was evaluated with the Emory Functional Ambulation Profile (E-FAP).
      Data were summarized with mean and standard deviation and further analyzed using
      the Pearson product moment correlation at 0.05 alpha level. Participants bore
      60.3% (SD =7.1%) of their body weights on the unaffected legs and had a mean PWBA
      of 20.8 % (SD=14.7%). There was a significant positive correlation (r = 0.675, p
      < 0.0001) between PWBA and total E-FAP scores of participants. PWBA could hence
      be used to monitor functional ambulation recovery in stroke survivors.

PMID- 22980156
TI  - Pandemic influenza A (H1N1) and its prevention: a cross sectional study on
      patients' knowledge, attitude and practice among patients attending primary
      health care clinic in Kuala Lumpur, Malaysia.
AB  - The World Health Organization confirmed that the novel influenza A, H1N1 as a
      pandemic on 11 June 2009. After less than three months, 182 countries were
      affected by the pandemic accounting for about 150,000 infected cases and 3000
      mortality. Successful H1N1 pandemic management strategies' shaped by making
      changes in health behavior. The aim of this study was to document patients'
      knowledge, attitudes and practices (KAP) regarding the pandemic influenza A
      (H1N1) and its prevention. We performed a cross-sectional study on knowledge,
      attitudes and practices (KAP) on preventive measures of Influenza A (H1N1)
      involving 322 patients attending Klinik Kesihatan Jinjang, a primary health care
      clinic in Kuala Lumpur, Malaysia from May 10 to 26, 2010 using a face to face
      interview with a structured pre-tested questionnaire. The majority of the
      respondents were females (56.8%), Malays (43.2%) aged between 18-27 years old
      (28.9%). There were significant association between knowledge on the complication
      of H1N1, effectiveness of the treatment, preventive measures of Influenza A
      (H1N1) and race (p<0.001) and educational level (p<0.001). There were also
      significant associations between attitude scores of these patients and their
      gender (p=0.03), and educational level (p=0.001). Practice scores related to H1N1
      were found to be significantly associated with race (p<0.001) and educational
      level (p<0.001). The significant associations were observed between knowledge and
      attitude (p<0.001), knowledge and practices (p<0.001), as well as attitude and
      practices related to H1N1 (p<0.001). Knowledge has a crucial effect on patients'
      attitude and practice particularly in a pandemic spread. So health policy makers
      should attempt to disseminate information about preventive measures to community
      in order to improve their preventive practices during pandemics.

PMID- 22980157
TI  - Seasonal variation of malaria parasite density in paediatric population of
      Northeastern Nigeria.
AB  - Malaria is a major cause of morbidity and mortality in children and adults in the
      Sudano Sahel of Northeastern Nigeria with the highest prevalence of malaria in
      pregnancy of 64.5 in Nigeria recorded in this region. This study was carried out
      in 2003 and 2004 to provide parasitological baseline data for the development of
      Malaria Early Warning System (MEWS) for the surveillance of type I epidemic
      caused by meteorological conditions and to provide data for timing malaria key
      vector control measures such as Indoor Residual Spraying (IRS) for maximum
      effect. Clinical information about malaria cases were used in this study. In all
      692 children aged 6 to 96 months were screened for Plasmodium infection and used
      for the analysis. The results showed that the majority of infected children
      (68.06%) were aged 12-60 months and their asexual parasite density (ap/ u1) was
      between 100-500 ap/u1 of the whole blood. The month of September recorded the
      highest Geometric Mean Asexual-Densities (GMPD) of 13,655 while the lowest
      parasite densities were observed at the peak of the dry season, especially during
      the months of March and April. Significance difference (p<0.05) was observed
      between the sexes in infection rate. It is obvious that male children have higher
      infection rate (about 67.5%), than while female children (32.5%) regardless of
      climate seasonality. Designing a malaria early warning system and providing
      baseline parasitological data for timing of spraying cycles for key malaria
      vector control measures such as Indoor Residual Spraying (IRS) should be
      encouraged to complement other effective malaria control strategies .Hence the
      need for this investigation.

PMID- 22980158
TI  - Impact of family planning health education on the knowledge and attitude among
      Yasoujian women.
AB  - The aim of this study was to determine the effect of health education on the
      knowledge and attitude regarding family planning and contraception's method among
      the women who obligatory attended the Premarital Counseling Center in Yasouj
      city, Iran. An experimental study was carried out and a total of 200 women were
      selected for the study using convenience sampling method among women who attended
      in the health centre in order to utilize the necessary premarital actions.
      Respondents were divided by two experimental and control groups randomly. A pre
      evaluation was done on the knowledge and attitude on family planning using a
      structured questionnaire. After which, the health education for experimental
      group was done within four educational sessions during 4 consecutive weeks and
      control group underwent traditional education method. Post evaluation was
      utilized for any changes regarding their knowledge and attitude among the
      respondents immediately after the intervention. Independent and paired t-test was
      used to evaluate the mean knowledge and attitude scores differences among both
      groups. RESULTS showed that there was a significant improvement in respondents'
      knowledge and attitude after educational program in experimental group (p<0.001),
      while no significant difference was observed in knowledge and attitude of control
      group. The finding also indicated that age was significantly associated with the
      level of respondents' knowledge. These results deal the effectiveness of the
      educational method. In conclusion, the educational method is effective in
      increasing the knowledge and improving the attitude of women regarding family
      planning in Yasouj compared to current used educational method. Future
      educational programs need to incorporate the features that have been associated
      with successful interventions in the past, as well as including their own
      evaluation procedures.

PMID- 22980159
TI  - Assessing quality of life in older adult patients with skin disorders.
AB  - Older adults experience a number of skin diseases and disorders that
      substantially affect quality of life. In the last two decades, a number of
      instruments have been developed for use among general dermatology patients to
      assess the effects of treatment and disease progression, perceptions of well
      being, and the value that patients place on their dermatologic state of health.
      This chapter reviews some health-related quality of life (HRQoL) (HRQoL) measures
      developed and validated specifically for dermatological conditions. However,
      opportunity exists for developing and validating HRQoL measures specifically for
      dermatological conditions most pertinent to older patients.  

PMID- 22980160
TI  - Maternal mortality among tribal women at a tertiary level of care in Bastar,
      Chhattisgarh.
AB  - OBJECTIVES: The primary objective of this study is to study Maternal Mortality as
      per Gravidity among Tribal women at a tertiary level of care in Bastar,
      Chhattisgarh, India. MATERIALS AND METHODS: This is a hospital based
      ,retrospective, reproductive-age mortality study (RAMOS) of tribal women of
      Bastar region, Chhattisgarh, that were admitted and managed in Obstetrics and
      Gynecology Department Govt. Medical College, Jagdalpur, Bastar, Chhattisgarh,
      between July 2007 and October 2011. There were total 120 cases. RESULT: Results
      of the present study showed that among 120 deceased tribal women highest maternal
      mortality 65 cases (54.166%) was noted in Primigravida (Nullipara G1P0), second
      highest maternal mortality 44 cases (38.333%) was noted in 2nd to 4th Gravida
      (Multipara), 10 cases (8.333%) were in 6th and 7th Grand Multigravida (Grand
      Multipara), and 01 case (0.833%) was in 8th Great Grand Multigravida. Direct
      causes of maternal mortality were highest 46 cases (38.333%) due to hypertensive
      disorders of pregnancy. Among direct causes second highest 18 cases (14.999%)
      maternal mortality were due to Rupture Uterus, third highest 12 cases (09.999%)
      of Septicemia, 06 cases (04.999%) of obstructed labor, 06 (04.999%) of
      Hemorrhage, 02 cases (01.666%) of unsafe Abortion, 02 cases (01.666%) of
      Pulmonary Embolism and 01 case (0.833%) due to Aspiration. Indirect causes of
      maternal mortality maximum 15 cases (12.5%) of Malaria and 10 cases (08.333%)
      were due to Anemia and 02 cases (01.666%) were of Sickle cell Anemia. The result
      of the present study showed that in tertiary level of care of Bastar in the year
      2007 - 2008, 2008 - 2009, 2009 - 2010 and 2010 - 2011 the total maternal deaths
      were 34 (n=34); 35 (n=35); 27 (n=27) and 26 (n=26) respectively. The Maternal
      Mortality Ratio was 1611.876; 1615.881; 1168.325 and 1000.769 Per 1, 00,000 live
      births in the year 2007- 2008; 2008 - 2009; 2009 - 2010 and 2010 - 2011
      respectively. In the year 2007 - 2008, maternal mortality percentage among tribal
      women was 80.314%; in the year 2008-2009 was 85.714% and was 100% in the year
      2009 - 2010 and 2010 - 2011. DISCUSSION: Discusses and/or relates this study's
      results to the need for improvement in the maternal health of tribal women of
      Bastar. It has been discussed well in the conclusion section.

PMID- 22980161
TI  - Knowledge, attitude and practice towards standard isolation precautions among
      Iranian medical students.
AB  - OBJECTIVE: Health care workers especially medical students are at risk of being
      exposed to blood-borne pathogens. Therefore, the aim of this study was to
      determine the knowledge, attitude and practice of medical students towards
      standard isolation precautions (SIP). METHODS: A standardized questionnaire was
      completed by 148 medical students from April to July of year 2009 to seek their
      knowledge, attitude and practice towards standard isolation precautions in a
      clinical setting at Qazvin University of Medical Sciences, Iran. RESULTS: The
      mean score of knowledge, attitude and practice towards standard isolation
      precautions were 6.8+/-2.1 (maximum 10), 16.6+/-4.2 (maximum 20), and 18.05 +/-
      4.5 (maximum 30) respectively. Significant differences were observed between
      practice of female and male (P < 0.008) and also knowledge of year 6 and year 7
      students (P <0.021). DISCUSSION: Education on infection control based on standard
      isolation precaution must be stressed and barriers of appropriate practice must
      be removed.

PMID- 22980162
TI  - Prevalence of overweight in high school students with special reference to
      cardiovascular efficiency.
AB  - BACKGROUND: In India, malnutrition has two ends. Under nutrition attracted the
      focus of health workers, as it is more prevalent. But over the past few years,
      childhood obesity is increasingly being observed with the changing lifestyle of
      families with increased purchasing power, increasing hours of inactivity due to
      television, video games and computers have replaced outdoor games and other
      social activities. Globally, an estimated 10% of school-aged children, between 5
      and 17 years of age, are overweight and obese. Obesity can be seen as first wave
      of a defined cluster of non-communicable diseases called "New World Syndrome"
      creating an enormous socio-economic and public health burden in poorer countries.
      The most important consequence of childhood obesity is its persistence into
      adulthood with all its health risks like dyslipidemia, hyper-insulinemia,
      cardiovascular diseases, type 2 diabetes, osteoarthritis, gall bladder disease,
      hypertension and some sex hormone- sensitive cancers. The present study was,
      therefore, undertaken to determine the prevalence of overweight in high school
      students and to study the association between Body Mass Index (BMI) and
      cardiovascular efficiency. METHODOLOGY: A school based cross sectional study was
      conducted in 2 schools of Nagpur. The total number of students included in the
      study was 565. Student's complete information regarding profile was taken in
      pretested questionnaire format after taking informed consent of parents. The
      anthropometric measurements of the students were done. Student's height and
      weight were measured and BMI was calculated. The student's cardiovascular
      efficiency was assessed with the help of Harvard step test. STATISTICAL ANALYSIS:
      The data was analyzed using Epi info version 3.4.1 software. Chi-square test was
      used as test of significance and p value less than 0.05 was considered as
      significant. RESULTS: 90.97% students belonged to 13, 14 and 15 years of age
      group. majority of the students belong to 14 years (33.81), followed by 13 years
      (33.27) and 15 years (23.89) of age group respectively. The prevalence of
      overweight in students was 5.84% and obesity was 0.35%. The combined prevalence
      of overweight and obesity was 6.19%. The prevalence of overweight in boys is
      5.31% and obesity was 0.63% and that in girls is 6.53% and 0% respectively. The
      association between Harvard step test and overweight was found to be
      statistically significant (p< 0.000001). CONCLUSION: The total prevalence of
      overweight and obesity was 6.19%. The association between Harvard step test and
      overweight was found to be statistically significant (p< 0.000001).

PMID- 22980163
TI  - Clinical Pearls in breast disease.

PMID- 22980164
TI  - Asthma and proinflammatory conditions: a population-based retrospective matched
      cohort study.
AB  - OBJECTIVE: To determine the association between asthma and proinflammatory
      conditions. PARTICIPANTS AND METHODS: This population-based retrospective matched
      cohort study enrolled all asthmatic patients among Rochester, Minnesota,
      residents between January 1, 1964, and December 31, 1983. For each asthmatic
      patient, 2 age-and sex-matched nonasthmatic individuals were drawn from the same
      population. The asthmatic and nonasthmatic cohorts were followed forward in the
      Rochester Epidemiology Project diagnostic index for inflammatory bowel disease
      (IBD), rheumatoid arthritis (RA), diabetes mellitus (DM), and coronary heart
      disease (CHD) as outcome events. Data were fitted to Cox proportional hazards
      models. RESULTS: We identified 2392 asthmatic patients and 4784 nonasthmatic
      controls. Of the asthmatic patients, 1356 (57%) were male, and mean age at asthma
      onset was 15.1 years. Incidence rates of IBD, RA, DM, and CHD in nonasthmatic
      controls were 32.8, 175.9, 132.0, and 389.7 per 100,000 person-years,
      respectively; those for asthmatic patients were 41.4, 227.9, 282.6, and 563.7 per
      100,000 person-years, respectively. Asthma was associated with increased risks of
      DM (hazard ratio, 2.11; 95% confidence interval, 1.43-3.13; P<.001) and CHD
      (hazard ratio, 1.47; 95% confidence interval, 1.05-2.06; P=.02) but not with
      increased risks of IBD or RA. CONCLUSION: Although asthma is a helper T cell type
      2-predominant condition, it may increase the risks of helper T cell type 1
      polarized proinflammatory conditions, such as CHD and DM. Physicians who care for
      asthmatic patients need to address these unrecognized risks in asthmatic
      patients.

PMID- 22980165
TI  - The nucleus accumbens as a potential target for central poststroke pain.
AB  - Although deep brain stimulation (DBS) has been found to be efficacious for some
      chronic pain syndromes, its usefulness in patients with central poststroke pain
      (CPSP) has been disappointing. The most common DBS targets for pain are the
      periventricular gray region (PVG) and the ventralis caudalis of the thalamus.
      Despite the limited success of DBS for CPSP, few alternative targets have been
      explored. The nucleus accumbens (NAC), a limbic structure within the ventral
      striatum that is involved in reward and pain processing, has emerged as an
      effective target for psychiatric disease. There is also evidence that it may be
      an effective target for pain. We describe a 72-year-old woman with a large right
      hemisphere infarct who subsequently experienced refractory left hemibody pain.
      She underwent placement of 3 electrodes in the right PVG, ventralis caudalis of
      the thalamus, and NAC. Individual stimulation of the NAC and PVG provided
      substantial improvement in pain rating. The patient underwent implantation of
      permanent electrodes in both targets, and combined stimulation has provided
      sustained pain relief at nearly 1 year after the procedure. These results suggest
      that the NAC may be an effective DBS target for CPSP.

PMID- 22980167
TI  - Canal configuration in the mesiobuccal root of the maxillary first molar and its
      endodontic significance. 1969.

PMID- 22980166
TI  - Comparison of the effect of the metabolic syndrome and multiple traditional
      cardiovascular risk factors on vascular function.
AB  - OBJECTIVE: To assess the effect of the metabolic syndrome (MetS) on endothelial
      function and compare these findings to those in individuals with a similar burden
      of traditional cardiovascular (CV) risk factors (>= 3) without MetS. PATIENTS AND
      METHODS: Both MetS and multiple CV risk factors were identified from 1103
      individuals who underwent the evaluation of endothelial function at the Mayo
      Clinic, in Rochester, Minnesota, from July 1, 2000, through July 31, 2011.
      Endothelial function was measured using digital arterial tonometry by assessing
      reactive hyperemia-induced vasodilation in one arm and adjusting for changes in
      the contralateral arm (reactive hyperemia index [RHI]). RESULTS: A total of 316
      individuals with MetS and 210 with multiple risk factors were assessed.
      Endothelial dysfunction was more pronounced in the MetS group compared with the
      multiple risk factor group (mean +/- SD natural logarithmic RHI, 0.61 +/- 0.25
      and 0.68 +/- 0.28, respectively; P=.006). Leukocyte count (7.00 +/- 1.89 *
      10(9)/L vs 6.41 +/- 1.76 * 10(9)/L, respectively; P=.001) and high-sensitivity C
      reactive protein level (1.78 +/- 1.53 mg/L vs 1.48 +/- 1.42 mg/L, respectively;
      P=.01) were higher in the MetS group compared with the multiple risk factor
      group. After adjustment for covariates and 6 traditional CV risk factors in a
      multivariate regression model, MetS had a significant and independent influence
      on natural logarithmic RHI (beta=-.11; P=.01). CONCLUSION: The current study
      found that individuals with MetS have a higher degree of endothelial dysfunction
      and inflammation compared with individuals with multiple CV risk factors and may
      therefore have an increased CV risk beyond the contributions of multiple
      traditional risk factors.

PMID- 22980168
TI  - Effect of different apical preparation sizes on outcome of primary endodontic
      treatment: a randomized controlled trial.
AB  - INTRODUCTION: The study was designed as a randomized controlled trial to evaluate
      the effect of the apical preparation size in relation to the first apical binding
      file (FABF) on the outcome of primary endodontic treatment in mandibular first
      molars. METHODS: One hundred sixty-seven patients met the inclusion criteria.
      They were randomly allocated to 5 different endodontic treatment groups (ie, A,
      B, C, D, and E) in which canals were enlarged to 2, 3, 4, 5, and 6 sizes larger
      than the FABF, respectively. One hundred twenty-nine patients were evaluated at
      the 12-month follow-up. The primary outcome measure was the change in periapical
      radiolucency as assessed by periapical index (PAI) scores. The clinical finding
      constituted the secondary outcome measure. RESULTS: A statistically significant
      reduction in PAI scores was observed in all groups (P < .001). The proportion of
      successfully healed cases increased with an increase in the apical preparation
      size with 48%, 71.43%, 80%, 84.61%, and 92% successful healing observed in groups
      A to E, respectively. However, statistical analysis revealed that only group A
      showed significantly less improvement than other groups (P < .05). No significant
      difference was observed between the rest of the groups. Regression analysis
      revealed a significant and positive association between the master apical
      preparation size and an improvement in PAI scores (beta = 0.037, P = .001).
      CONCLUSIONS: The enlargement of the canal to 3 sizes larger than the FABF is
      adequate, and further enlargement does not provide any additional benefit during
      endodontic treatment.

PMID- 22980169
TI  - Lesion progression in post-treatment persistent endodontic lesions.
AB  - INTRODUCTION: Radiographic lesions related to root-filled teeth may persist for
      long periods after treatment and are considered to indicate failure of initial
      treatment. Persistent lesions are found in a proportion of cases, but information
      on lesion progression is lacking. This study examined the incidence of lesion
      improvement, remaining unchanged, and deterioration among persistent lesions in a
      group of patients recruited from a university-based clinic and identified
      potential predictors for lesion progression. METHODS: Patients of a university
      clinic with persistent endodontic lesions at least 4 years since treatment and
      with original treatment radiographs available were recruited with informed
      consent. Data were obtained by interview and from dental records and clinical and
      radiographic examinations. Univariate and multivariate statistical analyses were
      carried out by using SPSS (version 19). RESULTS: One hundred fifty-one persistent
      lesions were identified in 114 patients. A majority of the lesions (107, 70.9%)
      received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%)
      improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since
      treatment. Potential predictors for lesions that did not improve included recall
      lesion size, pain on biting at recall examination, history of a postobturation
      flare-up, and a non-ideal root-filling length (P < .05). Lesions that had
      persisted for a longer period appeared less likely to be improving (relative
      risk, 1.038; 95% confidence interval, 1.000-1.077). CONCLUSIONS: A specific time
      interval alone should not be used to conclude that a lesion will not resolve
      without intervention. This study identified several clinical factors that are
      associated with deteriorating persistent lesions, which should aid in identifying
      lesions that require further intervention.

PMID- 22980170
TI  - Patient preferences regarding 1-visit versus 2-visit root canal therapy.
AB  - INTRODUCTION: Patient preferences should be taken into account by clinicians when
      treatment planning. The purposes of this study were to describe the number of
      visits patients preferred when undergoing root canal therapy (RCT) and to assess
      whether their preferences were related to hypothetical treatment success rates.
      METHODS: Self-administered questionnaires were mailed to 351 consecutive patients
      scheduled for initial RCT appointments in the University of Iowa College of
      Dentistry's graduate or faculty endodontic clinic. The questionnaires ascertained
      demographic information; preferences for 1-visit versus 2-visit RCT given
      different hypothetical success rate scenarios for the 2 approaches, as well as
      patient dental history. Univariate frequency distributions were generated, and
      relationships between hypothetical success rates and patient preferences were
      evaluated. RESULTS: Questionnaires were returned by 124 patients (35% response).
      Given equal success rates, 78% of respondents preferred 1-visit RCT, compared
      with 7% who preferred 2-visit RCT and 16% who would follow their dentist's
      recommendation. As success rates for 2-visit RCT went from equal to 5% better to
      10% better to 20% better compared with 1-visit RCT, the proportion of respondents
      who preferred 2-visit RCT increased from 7% to 34% to 46% to 65%, respectively.
      Regardless of success rates, approximately 5% of respondents said they would
      prefer 2-visit RCT, and 20% would do whatever their dentist recommended.
      CONCLUSIONS: Although most respondents preferred 1-visit RCT regardless of
      success rates, many would prefer 2-visit RCT if its success rate were greater
      than that of 1-visit RCT. This finding confirms the importance of discussing
      success rates and considering patients' wishes when treatment planning.

PMID- 22980171
TI  - A prospective study of the extraction and retention incidence of endodontically
      treated teeth with uncertain prognosis after endodontic referral.
AB  - INTRODUCTION: The present study was conducted with the aim to assess the
      extraction and retention incidence of endodontically treated teeth with an
      uncertain prognosis after endodontic referral and to evaluate the factors related
      to the decision-making process. METHODS: Two hundred seventy-five permanent teeth
      were clinically and radiographically evaluated by 3 experienced endodontists. The
      type of tooth, age and sex of the patients, the motive of referral, and the main
      chief complaint were the initial recorded data. The associations between
      extraction reasons and the patients' age and sex or tooth type were analyzed
      using the chi-square test. RESULTS: Of the 275 teeth examined, 217 (79%) were
      finally extracted. The remaining 58 (21%) teeth were endodontically retreated and
      restored. A questionable clinical status was the main motive for endodontic
      referral (57.1%). The teeth most extracted were maxillary molars (36.2%) followed
      by mandibular molars (32.9%). The most prevalent reason for extraction was
      nonrestorable caries (37.1%). The majority of the teeth retained in the oral
      cavity needed surgical periodontal or endodontic management. CONCLUSIONS: The
      most frequent reason responsible for the fate of endodontically treated teeth is
      the pronounced loss of dental tissues. Endodontic referral may aid in the
      survival of some carefully selected cases of endodontically treated teeth.

PMID- 22980172
TI  - Mahidol study 1: comparison of radiographic and survival outcomes of immature
      teeth treated with either regenerative endodontic or apexification methods: a
      retrospective study.
AB  - INTRODUCTION: There are numerous challenges in treating immature permanent teeth
      with a diagnosis of pulp necrosis. Three general treatment options are calcium
      hydroxide apexification, mineral trioxide aggregate (MTA) apexification, and
      revascularization. The objective of this retrospective study was to evaluate
      radiographic and clinical outcomes of immature teeth treated with 1 of these 3
      methods. METHODS: Clinical outcome data and radiographs were collected from 61
      cases (ie, 22 calcium hydroxide apexification cases, 19 MTA apexification cases,
      and 20 revascularization cases). Both tooth survival and clinical success rates
      were analyzed. In addition, the preoperative and recall radiographs were analyzed
      to calculate the percentage increase in root width and length. RESULTS: The
      percentage change of root width was significantly greater in the
      revascularization group (28.2%) compared with the MTA apexification (0.0%) and
      calcium hydroxide apexification groups (1.5%). In addition, the percentage
      increase of root length was significantly greater in the revascularization group
      (14.9%) compared with the MTA (6.1%) and calcium hydroxide apexification groups
      (0.4%). Moreover, the survival rate of the revascularization-treated teeth (100%)
      and MTA apexification-treated teeth (95%) were greater than the survival rates
      observed in teeth treated with calcium hydroxide (77.2%). CONCLUSIONS: In this
      study, revascularization was associated with significantly greater increases in
      root length and thickness in comparison with calcium hydroxide apexification and
      MTA apexification as well as excellent overall survival rates.

PMID- 22980173
TI  - Effect of preoperative alprazolam on the success of inferior alveolar nerve block
      for teeth with irreversible pulpitis.
AB  - INTRODUCTION: Success of inferior alveolar nerve (IAN) block decreases in
      patients with irreversible pulpitis. The purpose of this study was to evaluate
      the effect of preoperative administration of alprazolam on the success of the IAN
      block for teeth with irreversible pulpitis. METHODS: Sixty patients with
      irreversible pulpitis of a mandibular molar were selected for this prospective,
      randomized, double-blind, placebo-controlled study. The patients received
      identical capsules of either 0.5 mg of alprazolam or placebo 45 minutes before
      the administration of a conventional IAN block. Access cavity preparation was
      initiated 15 minutes after the IAN block injection. Lip numbness was recorded for
      all the patients. Success was defined as no or mild pain on the basis of visual
      analogue scale recordings during access cavity preparation and initial
      instrumentation. Data were analyzed by t test, Mann-Whitney, and chi(2) tests.
      RESULTS: The success rate was 53% for alprazolam group and 40% for placebo group,
      with no significant difference between the 2 groups (P = .301). CONCLUSIONS:
      Within the scope of the current study, preoperative oral administration of 0.5 mg
      of alprazolam did not improve the success of the IAN block in mandibular molars
      in patients with irreversible pulpitis, and the success rate was not adequate to
      ensure profound pulpal anesthesia.

PMID- 22980174
TI  - Effect of maintaining apical patency on irrigant penetration into the apical two
      millimeters of large root canals: an in vivo study.
AB  - INTRODUCTION: Factors such as complex root canal anatomy and the vapor lock
      phenomenon have been shown to limit the penetration of irrigating solutions into
      the apical third in both in vivo and in vitro studies involving small and wide
      canals. Hence, the aim of this study was to determine whether the use of a
      patency file is related to the presence of a radiopaque irrigating solution in
      the apical 2 mm of large human root canals. METHODS: Forty-three large human root
      canals were randomly divided into 2 groups. Apical patency was maintained in 1
      group (P, n = 22) during shaping and cleaning procedures with a no. 10 K-file 1
      mm beyond the working length (WL) but not in the other group (no patency [NP], n
      = 21). In both groups, the canals were shaped with the K3 system. Irrigation was
      performed with 1 mL of a solution prepared with a radiopaque contrast medium and
      5.25% sodium hypochlorite. Digital images were taken, and 2 calibrated readers
      determined the presence or absence of the irrigating solution in the apical 2 mm
      of the root canals. RESULTS: There were significantly more canals with irrigant
      in the apical 2 mm when apical patency was maintained with a no. 10- Kfile 1 mm
      beyond the WL than when apical patency was not maintained throughout the cleaning
      and shaping procedures (P = .04). CONCLUSIONS: Maintaining apical patency
      improves the delivery of irrigants into the apical third of large human root
      canals.

PMID- 22980175
TI  - Detection of vertical root fractures in vivo in endodontically treated teeth by
      cone-beam computed tomography scans.
AB  - INTRODUCTION: The presence of a vertical root fracture (VRF) in an endodontically
      treated tooth has an immense impact on the treatment's outcome. Early diagnosis
      of a VRF is imperative to avoid overtreatment and extensive bone loss. Our study
      aimed to examine the validity of 2 cone-beam computed tomography (CBCT) scanners
      in detecting VRFs in endodontically treated teeth in vivo. METHODS: Thirty-nine
      endodontically treated teeth suspected of VRFs from 39 patients were included. No
      fracture line was visible in periapical radiographs. Two limited-field-of-view
      scanners were used, the NewTom 3G and the 3D Accuitomo 170. Three observers
      evaluated the CBCT images independently and twice. The most frequently given
      score was used to calculate the validity of the CBCT systems. The findings of
      orthograde retreatment, endodontic microsurgery, or extraction were the gold
      standard. The intraobserver agreement (Cohen kappa) and the interclass
      correlation coefficients were calculated. RESULTS: The sensitivity, specificity,
      and accuracy for the NewTom 3G were 75%, 56%, and 68%, respectively, and for the
      3D Accuitomo 170 they were 100%, 80%, and 93%, respectively. The positive
      predictive value and the negative predictive values were 75% and 55%,
      respectively, for NewTom 3G and 90% and 100%, respectively, for 3D Accuitomo 170.
      CONCLUSIONS: The results of our study support the use of 3D Accuitomo 170 for the
      detection of VRFs in endodontically treated teeth. They also suggest that the
      reproducibility and accuracy in VRF detection depend on the CBCT system used.

PMID- 22980176
TI  - Alteration of microRNA expression of human dental pulp cells during odontogenic
      differentiation.
AB  - INTRODUCTION: MicroRNAs (miRNAs) play momentous roles in various biological
      processes including cell differentiation. However, little is known about the role
      of miRNAs in human dental pulp cells (hDPCs) during odontogenic differentiation.
      The aims of this study were to investigate the expression of miRNAs in the
      primary culture of hDPCs when incubated in odontogenic medium. METHODS: The
      potential characteristics of hDPCs were investigated by miRNA microarray and real
      time reverse transcriptase polymerase chain reaction. Bioinformatics (ie, target
      prediction, Gene Ontology analysis, and Kyoto Encyclopedia of Genes and Genomes
      mapping tools) were applied for predicting the complementary target genes of
      miRNAs and their biological functions. RESULTS: A total of 22 miRNAs were
      differentially expressed in which 12 miRNAs up-regulated and 10 miRNAs down
      regulated in differentiated hDPCs compared with the control. The target genes of
      differential miRNAs were predicted to associate with several biological functions
      and signaling pathways including the mitogen-activated protein kinase (MAPK) and
      the Wnt signaling pathway. CONCLUSIONS: The differential expression miRNAs may be
      involved in governing hDPC odontogenic differentiation, thus contributing to the
      future investigations of regulatory mechanisms in reparative dentin formation and
      dental pulp regeneration.

PMID- 22980177
TI  - Voltage-dependent sodium channels and calcium-activated potassium channels in
      human odontoblasts in vitro.
AB  - INTRODUCTION: Transmembrane ionic signaling regulates many cellular processes in
      both physiological and pathologic settings. In this study, the biophysical
      properties of voltage-dependent Na(+) channels in odontoblasts derived from human
      dental pulp (HOB cells) were investigated together with the effect of bradykinin
      on intracellular Ca(2+) signaling and expression of Ca(2+)-activated K(+)
      channels. METHODS: Ionic channel activity was characterized by using whole-cell
      patch-clamp recording and fura-2 fluorescence. RESULTS: Mean resting membrane
      potential in the HOB cells was -38 mV. Depolarizing steps from a holding
      potential of -80 mV activated transient voltage-dependent inward currents with
      rapid activation/inactivation properties. At a holding potential of -50 mV, no
      inward current was recorded. Fast-activation kinetics exhibited dependence on
      membrane potential, whereas fast-inactivation kinetics did not. Steady-state
      inactivation was described by a Boltzmann function with a half-maximal
      inactivation potential of -70 mV, indicating that whereas the channels were
      completely inactivated at physiological resting membrane potential, they could be
      activated when the cells were hyperpolarized. Inward currents disappeared in
      Na(+)-free extracellular solution. Bradykinin activated intracellular Ca(2+)
      releasing and influx pathways. When the HOB cells were clamped at a holding
      potential of -50 mV, outward currents were recorded at positive potentials,
      indicating sensitivity to inhibitors of intermediate-conductance Ca(2+)-activated
      K(+) channels. CONCLUSIONS: Human odontoblasts expressed voltage-dependent Na(+)
      channels, bradykinin receptors, and Ca(2+)-activated K(+) channels, which play an
      important role in driving cellular functions by channel-receptor signal
      interaction and membrane potential regulation.

PMID- 22980178
TI  - Presence of myofibroblasts and matrix metalloproteinase 2 in radicular cysts,
      dentigerous cysts, and keratocystic odontogenic tumors: a comparative
      immunohistochemical study.
AB  - INTRODUCTION: The aim of this study was to analyze the presence of myofibroblasts
      and matrix metalloproteinase 2 (MMP-2) in radicular cysts (RCs), dentigerous
      cysts (DCs), and keratocystic odontogenic tumors (KOTs). METHODS: For the study,
      29 RCs, 19 DCs, and 15 KOTs were selected. Immunohistochemical reactions were
      performed by using anti-MMP-2 and anti-alpha-smooth muscle actin (SMA)
      antibodies. For the analysis, 10 high-power fields were observed in each case to
      determine the percentage of positive cells, which was classified as negative,
      weak, or strong. RESULTS: The presence of myofibroblasts (alpha-SMA-positive
      cells) was most common in KOTs (46.67%), followed by DCs (36.84%) and RCs
      (31.04%); however, it was not statistically significant (P = .8). The stromal MMP
      2 expression was positive in all lesions but 1 case of KOT. Most cases of RC and
      DC presented strong MMP-2 expression in the stroma, whereas half of the KOTs
      showed similar classification. The MMP-2 expression was commonly found in the
      epithelial lining of the lesions; it was strong in almost all KOTs. No
      correlation between epithelial and stromal MMP-2 and alpha-SMA expressions was
      observed. CONCLUSIONS: Myofibroblasts and MMP-2 are frequent in RCs, DCs, and
      KOTs and eventually can contribute to bone resorption, favoring the progression
      and growth of these lesions.

PMID- 22980179
TI  - Effects of calcium hydroxide on cytokine expression in endodontic infections.
AB  - INTRODUCTION: The use of calcium hydroxide is an effective step in killing
      bacteria that remain after cleaning and shaping procedures. It also induces hard
      tissue formation and is effective for stopping inflammatory exudates. METHODS:
      The aim of this study was to assay and to compare the influence of calcium
      hydroxide on periapical interstitial fluid from human root canals. The mRNA
      expression levels of the cytokines interferon (IFN)-gamma, tumor necrosis factor
      alpha, interleukin (IL)-1beta, IL-17A, and IL-10 as well as the chemokine MCP-1
      were assayed by real-time polymerase chain reaction immediately after root canal
      cleaning and 15 days later. RESULTS: Levels of IL-1beta, IFN-gamma, IL-10, and
      the chemokine CCL2/MCP-1 were increased in teeth without endodontic dressings.
      With calcium hydroxide interappointment dressings, no statistically significant
      changes were observed in cytokine mRNA expression. However, when comparing teeth
      that received the medication with those that did not, expression levels of IL
      1beta, IFN-gamma, and IL-10 were statistically lower in those teeth that received
      calcium hydroxide. CONCLUSIONS: Analyses of cytokines and the chemokine CCL-2/MCP
      1 demonstrated the benefits of calcium hydroxide as a root canal dressing because
      it impedes the increase of all mediators during the experimental time.

PMID- 22980180
TI  - Direct effect of intracanal medicaments on survival of stem cells of the apical
      papilla.
AB  - INTRODUCTION: Regenerative endodontic procedures are an alternative treatment for
      immature teeth with necrotic pulps. Typically, intracanal medicaments such as
      triple antibiotic paste (TAP) or double antibiotic paste (DAP) and calcium
      hydroxide (Ca[OH](2)) are used for disinfection. However, their effect on human
      stem cells of the apical papilla (SCAPs) is unknown. We hypothesized that
      intracanal medicaments at high concentrations are toxic to SCAPs. To test this
      hypothesis, a cell culture assay was used. METHODS: Briefly, SCAPs were cultured
      and subjected to either no drug treatment or various concentrations including
      TAP, DAP, modified TAP (ciprofloxacin, metronidazole and cefaclor), Augmentin
      (Champs Pharmacy, San Antonio, TX), or Ca(OH)(2). Viable stem cells counts were
      obtained using an automated method of detecting trypan blue dye at 3 days after
      treatment. RESULTS: All 4 antibiotics significantly reduced SCAP survival in a
      concentration-dependent fashion. Interestingly, Ca(OH)(2) was conducive with SCAP
      survival at all concentrations. CONCLUSIONS: Collectively, our data show that
      high concentrations of antibiotics have a detrimental effect on SCAP survival,
      whereas lower concentrations as well as Ca(OH)(2) at all tested concentrations
      are conducive with SCAP survival and proliferation. These studies highlight the
      clinically important point that intracanal medicaments must be used at
      concentrations that are bactericidal while having minimal effects on stem cell
      viability.

PMID- 22980181
TI  - Effectiveness of endodontic disinfecting solutions against young and old
      Enterococcus faecalis biofilms in dentin canals.
AB  - INTRODUCTION: Enterococcus faecalis is a species commonly isolated from
      persistent root canal infections. The purpose of this study was to compare the
      antibacterial effects of different disinfecting solutions on young and old E.
      faecalis biofilms in dentin canals using a novel dentin infection model and
      confocal laser scanning microscopy (CLSM). METHODS: The bacteria were introduced
      into the dentinal tubules by centrifugation. After 1 day and 3 weeks of
      incubation, 40 infected dentin specimens were subjected to 1 and 3 minutes of
      exposure to disinfecting solutions, which included 2% sodium hypochlorite (NaOCl)
      (EMD Chemicals Inc, Darmstadt, Germany), 6% NaOCl, 2% chlorhexidine (CHX) (Sigma
      Chemical Co, St Louis, MO), and QMiX (Dentsply Tulsa Dental, Tulsa, OK). The
      proportions of dead and live bacteria inside the dentinal tubules after exposure
      to these disinfectants were assessed by CLSM using a LIVE/DEAD bacterial
      viability stain. RESULTS: Significantly fewer bacteria were killed in the 3-week
      old dentin biofilm than in the 1-day-old biofilm. Three minutes of exposure
      resulted in more dead bacteria than 1 minute of exposure for both biofilms in all
      experimental groups (P < .05). Six percent NaOCl and QMiX were the most effective
      disinfecting solutions against the young biofilm, whereas against the 3-week-old
      biofilm, 6% NaOCl was the most effective followed by QMiX. Two percent NaOCl was
      equally effective as 2% CHX. All the disinfecting agents killed significantly
      more bacteria than the sterile water used as a negative control (P < .05).
      CONCLUSIONS: Within dentin canals, bacteria in established biofilms are less
      easily killed by endodontic medicaments than bacteria in young biofilms.

PMID- 22980182
TI  - Effect of canal preparation on fill length in straight root canals obturated with
      RealSeal 1 and Thermafil Plus.
AB  - INTRODUCTION: A common adverse effect when using thermoplasticized obturators is
      overextension. A canal preparation allowing for predictable obturation length
      would be of clinical value. This study compared straight canals instrumented to a
      size 40 file by evaluating the extension of 2 thermoplastic obturation systems, a
      0.04 standardized taper preparation (STP) and a varied taper preparation (VTP),
      by evaluating the extension of 2 thermoplastic obturation systems, RealSeal 1 (RS
      1) and Thermafil Plus (TP). METHODS: Eighty extracted mature human premolars with
      single straight canals were randomly divided into 4 experimental groups (n = 20).
      Groups 1 and 2 were instrumented to size 40/04 at working length with STP. Groups
      3 and 4 were instrumented to size 40/02 at working length with VTP. Groups 1 and
      3 were obturated with RS-1, and groups 2 and 4 were obturated with TP. All groups
      were obturated per manufacturer's instructions. Extension of material was
      evaluated and assessed ordinally. Statistically significant differences were
      determined by logistic regression with significance level set at P < .05.
      RESULTS: Significant differences in extrusion existed between groups 2 and 4 when
      controlling for type of material (P = .026) and all groups for extrusion of TP
      compared with RS-1 when controlling for type of preparation (P < .001).
      CONCLUSIONS: The results indicate that when filling with RS-1 obturators, the
      canal can be instrumented to an STP or VTP with a low likelihood of excessive
      extrusion. If the clinician prefers to use TP obturators, this study validates a
      VTP to decrease the occurrence of overextension.

PMID- 22980183
TI  - Assessment of influence of flexion angles of files in apical stop preparation by
      using manual and rotary instrumentation techniques.
AB  - INTRODUCTION: This study aimed to evaluate the influence of flexion angles
      produced by files during root canal instrumentation on the final form of the
      apical stop. METHODS: Sixty human lower incisors were divided into 3 groups (n =
      20). After access preparation and working length determination, radiographs were
      taken from a mesiodistal and buccolingual direction with #15 K-file inserted to
      working length. Teeth from FlexM group were instrumented with stainless steel
      Flexofiles up to #40 file. For ProM and ProR groups, hand ProTaper Universal and
      ProTaper Universal rotary files were used, respectively, up to file F4. New
      radiographs were taken as previously described. After gutta-percha insertion, the
      apex of each specimen was ground, allowing gutta-percha visualization, and an
      image of the apex was captured to identify root canal deformation with computer
      software. The flexion of files was evaluated from both initial and final
      radiographs as the angle formed between the divergence of the file path and its
      virtual image represented by the direction taken by the file in the absence of
      curvature. RESULTS: FlexM group presented the highest variation in flexion angles
      compared with ProM (P = .112) and ProR (P = .024) groups. Nickel-titanium rotary
      system (ProR) reduced apical stop deformation compared with the manual techniques
      that used nickel-titanium (P = .011) or stainless steel (P = .025) files.
      CONCLUSIONS: Force vectors caused by the flexion angles of the files during the
      instrumentation of curved canals promoted apical stop deformation. ProTaper
      Universal rotary files showed less apical deformation than hand ProTaper
      Universal and stainless steel files.

PMID- 22980184
TI  - Infection of apical dentin and root-end cavity disinfection.
AB  - INTRODUCTION: The purpose of this study was to assess Enterococcus faecalis
      penetration into the dentin of the apical 3 mm and bacterial death after the
      application of either chlorhexidine or laser to root-end cavities. METHODS: Root
      canals of 60 single-rooted teeth were prepared. In part 1, cementum was removed
      semicircumferentially from 21 roots, and the smear layer was removed from 15
      roots using 17% EDTA/cetrimide. Teeth were inoculated and incubated with E.
      faecalis for 10 days, rinsed, and live/dead stained. The effect of cementum and
      smear on bacterial penetration was assessed by confocal laser scanning microscopy
      (CLSM). In part 2, 39 teeth had root ends resected and cavities ultrasonically
      prepared. Inoculated roots were assigned to 1 of the following 3 groups: (1) root
      end cavities irrigated with 0.2 % chlorhexidine, (2) root-end cavities irradiated
      with a laser for 20 seconds at 1.5 W, or (3) root-end cavities that received no
      treatment. Roots were live/dead stained, sectioned, and examined by CLSM. The
      depth of the bacterial penetration and bacterial survival were compared using the
      Mann-Whitney U test. RESULTS: The presence of a smear layer and/or cementum did
      not significantly affect bacterial penetration. In root-end cavities,
      chlorhexidine was more effective than laser (P < .001), reducing bacterial
      viability by 93% versus 70% with a laser. CONCLUSIONS: E. faecalis invaded the
      entire width of dentin in the apical 3 mm irrespective of the smear layer and/or
      cementum. Chlorhexidine was more effective than laser in disinfecting root-end
      cavities.

PMID- 22980185
TI  - Effect of MTAD as a final rinse on removal of smear layer in ten-minute
      preparation time.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of MTAD as final
      rinse on removal of the smear layer subsequent to primary irrigation with 1.3%
      sodium hypochlorite (NaOCl) during 10-minute instrumentation periods. METHODS:
      Forty teeth were divided into 2 experimental groups, each containing 15 teeth,
      and 1 positive control group of 10 teeth. The canals were prepared with hand and
      rotary instruments. In the MTAD group, the root canals were flushed with 1.3%
      NaOCl solution during 10-minute instrumentation, and MTAD was used as the final
      rinse. In other experimental group, 5.25% NaOCl was used during instrumentation,
      and 17% ethylenediaminetetraacetic acid (EDTA) was used as the final rinse. In
      the positive control group, sterile distilled water was used for irrigation. The
      overall instrumentation period for each canal was 10 minutes. The amount of the
      smear layer and degree of erosion qualified according to the study by Torabinejad
      et al by using a scanning electron microscope. Data were analyzed by Kruskal
      Wallis and Mann-Whitney tests. All statistical analyses were set with a
      significance level of alpha = 0.05. RESULTS: In the positive control group,
      debris and heavy smear layer covered the root canal surface and the tubules. In
      MTAD group, moderate smear layer covered the root canal surface and the tubules.
      In EDTA group, there was no smear layer on surface of canals. There were
      significant differences between groups (alpha < 0.0001). Mann-Whitney test showed
      significant difference between experimental groups (alpha = 0.01). CONCLUSIONS:
      In 10-minute instrumentation period, the use of 5.25% NaOCl during
      instrumentation and 17% EDTA as the final rinse is more effective than using 1.3%
      NaOCl as primary irrigation and MTAD as final rinse on removal of the smear
      layer.

PMID- 22980186
TI  - Comparative evaluation of calcium hypochlorite and sodium hypochlorite on soft
      tissue dissolution.
AB  - INTRODUCTION: The aim of this study was to compare in vitro the tissue
      dissolution properties of 5% and 10% calcium hypochlorite (Ca(OCl)(2)) with two
      concentrations (1.36% and 4.65%) of proprietary sodium hypochlorite (NaOCl) on
      bovine muscle tissue. METHODS: The available chlorine concentration of each
      solution was determined using iodometric titration. Tissue specimens from bovine
      muscle were weight adjusted (50 +/- 5 mg). Ten tissue specimens in each group
      were immersed in 5 mL each test solution, removed after 5 minutes, blotted dry,
      and weighed. The process was repeated every 5 minutes with a fresh 5-mL aliquot
      of the test solution for 60 minutes or until complete tissue dissolution,
      whichever was quickest. The percentage weight loss of the specimens was
      calculated over the experimental period. RESULTS: Available chlorine
      concentrations of the irrigants ranged from 1.36% to 4.65%. All solutions
      dissolved tissue completely after 60 minutes except 5% Ca(OCl)(2) (99.4%
      dissolution). Between the 35- and 60-minute test readings, there were no
      significant differences between the solutions. Chlorax (4.65% NaOCl) (Cerkamed
      Group, Nisko, Poland) dissolved tissue quicker during the first 35 minutes (P <
      .05). In this period, the weight loss with 10% Ca(OCl)(2) differed from Chlorax
      at all time intervals except at 5 and 35 minutes (P < .05); 5% Ca(OCl)(2) showed
      no significant differences with 10% Ca(OCl)(2) and Tesco bleach (1.36% NaOCl)
      (Tesco Stores Ltd, Chestnut, UK) in the first 35 minutes except at the 5-minute
      measurement. CONCLUSIONS: Within the limitations of this study, Chlorax (4.65%
      NaOCl) dissolved tissue faster than the Ca(OCl)(2) solutions and Tesco thin
      bleach (1.36% NaOCl) over the first 35 minutes, but there were no significant
      differences among the solutions thereafter.

PMID- 22980187
TI  - Flexural stiffness and stresses in nickel-titanium rotary files for various pitch
      and cross-sectional geometries.
AB  - INTRODUCTION: Shape is the main determinant of mechanical performance for nickel
      titanium rotary instruments. This study evaluated how pitch and cross-sectional
      geometry affected flexural stiffness and stresses. METHODS: Finite element models
      of rotary instruments with 4 cross-sectional geometries (triangle, slender
      rectangle, rectangle, square) and 3 pitches (5-, 10-, 15-threads) were created,
      featuring superelastic nickel-titanium properties. All models had the same
      length, taper, and external peripheral radius; cross-sectional area and/or center
      core area varied. The clamped shaft was rotated axially, while the tip was
      deflected 5 mm. Flexural stiffness and maximum von Mises stresses were
      calculated. RESULTS: Stiffness and maximum stress decreased with decreasing pitch
      (increasing threads). Doubling or tripling the threads for the triangular or
      rectangular cross sections decreased the stiffness and stress 6% and 12%,
      respectively; square cross sections were less affected (1% and 3% decrease,
      respectively). Square cross sections (higher cross-sectional and center-core
      areas) had higher stiffness and stresses than other models with same deflection.
      Rectangular and triangular models with the same center-core areas had similar
      stresses, but the rectangular model was 30%-40% stiffer. The slender-rectangle
      had the smallest center-core area and the lowest stiffness and stresses. Both
      rectangular cross sections caused stiffness and stress variations with rotation
      angle (13% for slender-rectangle); larger pitch caused more variation.
      CONCLUSIONS: Under the same tip deflection (simulating canal curvature), flexural
      stiffness and stress correlated with center-core area. Increasing pitch increased
      flexural stiffness and stresses.

PMID- 22980188
TI  - Effect of combined digital imaging parameters on endodontic file measurements.
AB  - INTRODUCTION: This study assessed the effect of the combination of a dedicated
      endodontic filter, spatial resolution, and contrast resolution on the
      determination of endodontic file lengths. METHODS: Forty extracted single-rooted
      teeth were x-rayed with K-files (ISO size 10 and 15) in the root canals. Images
      were acquired using the VistaScan system (Durr Dental, Beitigheim-Bissingen,
      Germany) under different combining parameters of spatial resolution (10 and 25
      line pairs per millimeter [lp/mm]) and contrast resolution (8- and 16-bit
      depths). Subsequently, a dedicated endodontic filter was applied on the 16-bit
      images, creating 2 additional parameters. Six observers measured the length of
      the endodontic files in the root canals using the software that accompanies the
      system. The mean values of the actual file lengths and the measurements of the
      radiographic images were submitted to 1-way analysis of variance and the Tukey
      test at a level of significance of 5%. The intraobserver reproducibility was
      assessed by the intraclass correlation coefficient. RESULTS: All combined image
      parameters showed excellent intraobserver agreement with intraclass correlation
      coefficient means higher than 0.98. The imaging parameter of 25 lp/mm and 16 bit
      associated with the use of the endodontic filter did not differ significantly
      from the actual file lengths when both file sizes were analyzed together or
      separately (P > .05). When the size 15 file was evaluated separately, only 8-bit
      images differed significantly from the actual file lengths (P <= .05).
      CONCLUSIONS: The combination of an endodontic filter with high spatial resolution
      and high contrast resolution is recommended for the determination of file lengths
      when using storage phosphor plates.

PMID- 22980189
TI  - Influence of different angles of reciprocation on the cyclic fatigue of nickel
      titanium endodontic instruments.
AB  - INTRODUCTION: The purpose of this study was to evaluate cyclic fatigue fracture
      resistance of engine-driven nickel-titanium (K3XF) instruments under
      reciprocating movement in various angles. METHODS: Fifty K3XF size 40 taper 0.06
      nickel-titanium instruments were divided randomly into 5 groups of 10 each. All
      instruments were subjected to cyclic fatigue tests. Instruments in groups 1-4
      were tested by using different reciprocating motions, whereas instruments of
      group 5 (control group) were used in continuous rotation. All instruments were
      rotated or reciprocated until fracture occurred. Time to fracture was recorded,
      and data were statistically analyzed by using one-way analysis of variance,
      followed by Tukey honestly significant difference test for comparison between
      different groups. RESULTS: All reciprocating groups (groups 1-4) showed a
      significant increase in time to failure when compared with group 5 (continuous
      rotation) (P < .05). Mean time was significantly higher in group 1, followed by
      group 2. No significant difference was found between groups 3 and 4 (P = .251).
      Increasing the clockwise angle of reciprocation and consequently increasing the
      angle of progression for each reciprocation cycle reduced the resistance to
      cyclic fatigue. CONCLUSIONS: Movement kinematics (reciprocating movements in
      various angles) had a significant influence on the cyclic fatigue life of the
      tested nickel-titanium instruments.

PMID- 22980190
TI  - Depth of penetration of four resin sealers into radicular dentinal tubules: a
      confocal microscopic study.
AB  - BACKGROUND: The aim of this in vitro study was to evaluate the depth of
      penetration of 4 different endodontic resin sealers into the radicular dentinal
      tubules with the aid of confocal microscopy. METHODS: Eighty single-rooted teeth
      were instrumented and divided into 4 groups composed of 20 teeth each. The
      samples were obturated with AH Plus, RealSeal, EndoRez, and RoekoSeal resin
      sealers, respectively. The core material in all the groups was Resilon. The teeth
      were sectioned at the coronal, middle, and apical thirds and viewed under
      confocal microscope to determine the depth of penetration of the sealer into the
      dentinal tubules. RESULTS: The results showed that the maximum penetration was
      exhibited by RealSeal resin sealer, followed by AH Plus, RoekoSeal, and EndoRez.
      The coronal third showed the maximum penetration, followed by middle third and
      least at the apical third. CONCLUSION: Under the parameter of this study,
      RealSeal resin sealer exhibited the maximum penetration.

PMID- 22980191
TI  - Mechanical behavior of pathfinding endodontic instruments.
AB  - INTRODUCTION: This study compared the mechanical properties of 3 pathfinding
      endodontic instruments. METHODS: The test instruments were subjected to
      mechanical tests to evaluate resistance to bending (flexibility), buckling,
      cyclic fatigue, and torsional load in clockwise rotation. Data were statistically
      evaluated by analysis of variance and the Student-Newman-Keuls test for multiple
      comparisons. RESULTS: In the buckling resistance test, the highest values were
      observed for C-Pilot files (VDW, Munich, Germany) and the lowest for Scout RaCe
      (FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments. In the bending
      resistance test, the lowest flexibility was observed for the C-Pilot instrument,
      and no significant difference was observed between Scout RaCe and PathFile
      (Maillefer/Dentsply, Ballaigues, Switzerland) instruments. The ranking in the
      fatigue resistance test was the following: PathFile > Scout RaCe > C-Pilot, with
      statistically significant differences observed in the number of cycles to
      fracture between all the instruments. In the torsional assay, the angular
      deflection to fracture decreased in the following order: Scout RaCe > PathFile >
      C-Pilot. As for the maximum torque values, the ranking was as follows: C-Pilot >
      PathFile > Scout RaCe. CONCLUSIONS: Findings revealed that the stainless-steel C
      Pilot instrument showed increased resistance to buckling but decreased
      flexibility and cyclic fatigue resistance when compared with nickel-titanium
      pathfinding instruments. PathFile instruments showed the highest resistance to
      cyclic fatigue, and Scout RaCe files exhibited the highest angular deflection to
      fracture. The different mechanical behavior of the instruments indicates that the
      combined use of stainless steel hand instruments and rotary nickel-titanium
      instruments during the exploration of narrow curved canals may be necessary to
      exploit the best performance of each pathfinding instrument.

PMID- 22980192
TI  - Management of perforations: four cases from two private practices with medium- to
      long-term recalls.
AB  - INTRODUCTION: Perforation repair is a fairly common endodontic procedure, but
      most of the recall data in the endodontic literature are short-term (ie, 1-2
      years). The purpose of this article was to present 4 clinical cases of
      perforation repair with medium- to long-term recalls. METHODS: Four cases were
      selected with different clinical scenarios. Three nonsurgical cases were
      retreated, repaired with mineral trioxide aggregate, and restored. The fourth
      case was strictly a surgical repair. Recalls up to 13 years are presented.
      RESULTS: Perforation repair was shown to be successful in this case series, the
      teeth were preserved, and extraction was avoided. CONCLUSIONS: If managed
      properly, perforation repairs can result in long-term clinical success.

PMID- 22980193
TI  - Drawbacks and unfavorable outcomes of regenerative endodontic treatments of
      necrotic immature teeth: a literature review and report of a case.
AB  - INTRODUCTION: Endodontic treatment of immature necrotic teeth is challenging.
      Recently a biologically based treatment called regenerative endodontic treatment
      was introduced. Although regenerative endodontic treatment causes root
      development, there are several drawbacks and unfavorable outcomes that should be
      addressed. This article describes regenerative endodontic treatment of 2
      maxillary central incisors with poor root development outcomes. METHODS: A
      healthy 14-year-old female patient was referred. The patient had history of an
      impact trauma 6 years before the first visit. Clinical and radiographic
      examinations revealed that maxillary central incisors were immature and necrotic
      with symptomatic apical periodontitis. After local anesthesia, rubber dam
      isolation, and access cavity preparation each tooth was irrigated with 20 mL of
      NaOCl 5.25% and received triple antibiotic dressing (ciprofloxacin,
      metronidazole, minocycline) for 4 weeks. In the next visit, after eliminating
      antibiotic dressing, bleeding was induced inside the canals, and then the coronal
      thirds of the canals were sealed with mineral trioxide aggregate. A week later,
      both teeth were permanently restored. RESULTS: In clinical and radiographic
      follow-ups, both teeth were functional, periapical lesions were healed, and the
      apices formed. However, the roots were not developed. After 6 years, because of
      moderate discoloration and caries, both teeth received root canal therapy and
      were permanently restored with casting dowel core and full crown restorations.
      CONCLUSIONS: Criteria for case selection in regenerative endodontic treatments
      should be determined.

PMID- 22980194
TI  - Different representations of vertical root fractures detected by cone-beam
      volumetric tomography: a case series report.
AB  - INTRODUCTION: Vertical root fractures (VRFs) pose a clinical dilemma and a
      challenge to clinicians. Definitive diagnosis is often complicated by the lack of
      consistent signs and symptoms and the low sensitivity of conventional radiographs
      in the detection of VRFs. New radiographic imaging systems have recently become
      available for use in dentistry. Among these new imaging technologies is cone-beam
      volumetric tomography (CBVT). CBVT technology allows the precise visualization
      and evaluation of teeth with VRFs. The use of CBVT has great potential as a
      diagnostic tool to assist in the detection of VRFs. METHODS: Seven cases are
      presented to demonstrate the use of CBVT in detection of VRFs in endodontically
      treated teeth. RESULTS: Five specific findings on CBVT exam were consistent with
      confirmed VRFs. CONCLUSIONS: As demonstrated in this case series, CBVT can
      provide valuable additional diagnostic information in the detection of VRFs and
      may help prevent unnecessary treatment.

PMID- 22980196
TI  - Leptin and reproductive function.
AB  - Adipose tissue plays a dynamic role in whole-body energy homeostasis by acting as
      an endocrine organ. Collective evidence indicates a strong link between neural
      influences and adipocyte expression and secretion of leptin. Developmental
      changes in these relationships are considered important for pubertal transition
      in reproductive function. Leptin augments secretion of gonadotropin hormones,
      which are essential for initiation and maintenance of normal reproductive
      function, by acting centrally at the hypothalamus to regulate gonadotropin
      releasing hormone (GnRH) neuronal activity and secretion. The effects of leptin
      on GnRH are mediated through interneuronal pathways involving neuropeptide-Y,
      proopiomelanocortin and kisspeptin. Increased infertility associated with diet
      induced obesity or central leptin resistance are likely mediated through the
      kisspeptin-GnRH pathway. Furthermore, Leptin regulates reproductive function by
      altering the sensitivity of the pituitary gland to GnRH and acting at the ovary
      to regulate follicular and luteal steroidogenesis. Thus leptin serves as a
      putative signal that links metabolic status with the reproductive axis. The
      intent of this review is to examine the biological role of leptin with energy
      metabolism, and reproduction.

PMID- 22980195
TI  - Acetaminophen-induced liver injury in rats and mice: comparison of protein
      adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of
      toxicity.
AB  - Acetaminophen (APAP) overdose is the most common cause of acute liver failure in
      the West. In mice, APAP hepatotoxicity can be rapidly induced with a single dose.
      Because it is both clinically relevant and experimentally convenient, APAP
      intoxication has become a popular model of liver injury. Early data demonstrated
      that rats are resistant to APAP toxicity. As a result, mice are the preferred
      species for mechanistic studies. Furthermore, recent work has shown that the
      mechanisms of APAP toxicity in humans are similar to mice. Nevertheless, some
      investigators still use rats. New mechanistic information from the last forty
      years invites a reevaluation of the differences between these species. Comparison
      may provide interesting insights and confirm or exclude the rat as an option for
      APAP studies. To this end, we treated rats and mice with APAP and measured
      parameters of liver injury, APAP metabolism, oxidative stress, and activation of
      the c-Jun N-terminal kinase (JNK). Consistent with earlier data, we found that
      rats were highly resistant to APAP toxicity. Although overall APAP metabolism was
      similar in both species, mitochondrial protein adducts were significantly lower
      in rats. Accordingly, rats also had less oxidative stress. Finally, while mice
      showed extensive activation and mitochondrial translocation of JNK, this could
      not be detected in rat livers. These data support the hypothesis that
      mitochondrial dysfunction is critical for the development of necrosis after APAP
      treatment. Because mitochondrial damage also occurs in humans, rats are not a
      clinically relevant species for studies of APAP hepatotoxicity.

PMID- 22980197
TI  - The complex role of adiponectin in chronic kidney disease.
AB  - Although adiponectin, an adipocytokine released from adipose tissue, is thought
      to have anti-atherogenic, anti-inflammatory, and insulin-sensitizing effects, it
      appears that high, rather than low, circulating levels of adiponectin predict
      increased mortality in chronic kidney disease (CKD) patients in whom the
      circulating levels may rise to about three times higher than the levels in
      healthy subjects. As it could be hypothesized that in the uremic milieu high
      adiponectin levels reflect protein-energy wasting, lower residual renal function
      and/or volume overload, this may explain, at least in part, the observed
      paradoxical link between hyperadiponectinemia and poor outcome in CKD. To
      determine the biological consequences of high circulating adiponectin levels on
      carbohydrate and insulin metabolism as well as relations with cardiovascular
      function and mortality in the uremic milieu, further studies need to take into
      account both high-, and low-molecular weight adiponectin moieties as well as the
      role of adiponectin receptors. This brief review summarizes some of the recent
      advances in our understanding of the complex and context-sensitive role of this
      elusive and intriguing adipokine in the uremic milieu.

PMID- 22980198
TI  - Comparative studies of senescence-related enzymes in the cotyledon of chlorophyll
      b-deficient mutant and its wild type oilseed rape during senescence.
AB  - The change patterns of senescence-related enzymes during cotyledon senescence
      were studied in a chlorophyll (Chl) b-deficient mutant type (MT, Cr3529) and its
      wild type (WT) of Brassica napus L. seedlings. The fresh weight on the basis of
      cotyledon number initially increased till 20 days after planting (DAP) and then
      kept relative constant. The protein content decreased sharply since 20 DAP and
      Chl content reduced since 10 DAP in both types; however the rate of degradation
      in protein and Chl in the MT was slower than that in the WT since 20 DAP.
      Superoxide dismutase (SOD; E.C.1.15.1.1) activity declined in the WT but
      increased in the MT since 20 DAP. Activity of peroxidase (POD; E.C.1.11.1.7)
      increased markedly after 20 DAP in both types. Esterase (EST; E.C.3.1.1.1)
      activity increased in both types since 10 DAP, whereas at 40 DAP it was much
      lower in the MT than that in the WT. In addition, bands patterns of SOD, POD and
      EST isozymes were changed during cotyledon development in both types, but some
      differences were observed. Cu/ZnSODs activities were higher in the MT at 40 DAP
      as compared with the WT. These results showed that day 20 was the turning point
      during the cotyledon development and the senescence in the MT cotyledon was
      slower than that in the WT.

PMID- 22980199
TI  - Identification of novel drought-related mRNAs in common bean roots by
      differential display RT-PCR.
AB  - Drought is a major constraint for the production of common bean (Phaseolus
      vulgaris L.). To identify molecular responses to water deficit, we performed a
      differential display RT-PCR (DDRT) analysis using roots of bean plants grown
      aeroponically and submitted to dehydration. This allowed us to visualise 1200
      DDRT bands, 8.7% of which showed a clear regulation by dehydration, and to clone
      42 cDNAs, called PvD1 to PvD42. Among them, 20 early-dehydration-responsive cDNAs
      were selected by reverse northern that were induced or repressed before
      detectable water status changes and induction of ABA-regulated genes. Northern
      analysis for 16 PvD clones confirmed these early regulations and allowed us to
      identify four late dehydration-responsive genes. Their putative involvement in
      signalling, protein turn-over and translocation, chaperones as well as root
      growth modulations in response to water stress is discussed.

PMID- 22980200
TI  - Transgene structures suggest that multiple mechanisms are involved in T-DNA
      integration in plants.
AB  - To gain further understanding of the mechanisms involved in Agrobacterium
      mediated genetic transformation and T-DNA integration, we analysed 156 T
      DNA/rice, 69 T-DNA/T-DNA and 11 T-DNA/vector backbone (VB) junctions, which
      included 171 left borders (LB) and 134 right borders (RB). Conserved cleavage was
      observed in 6% of the LB and 43% of the RB. Terminal microhomology (1-10bp) was
      identified in 58% of T-DNA/rice, 43% of T-DNA/T-DNA and 82% of T-DNA/VB
      junctions, and this occurred particularly at the LB junctions. Approximately 32%
      of both T-DNA/rice and T-DNA/T-DNA junctions harboured 1-344bp of filler DNA that
      was derived mainly from the T-DNA region adjacent to the breakpoint and/or from
      the rice genome flanking the T-DNA integration site. Structure of the filler DNA
      was more complicated at the T-DNA/T-DNA junction than at the T-DNA/rice junction,
      indicating the presence of T-DNA recombination or rearrangement prior to or
      during T-DNA integration. When two T-DNAs were integrated in the inverted repeat
      configuration, significant truncation was always observed in one of the two T
      DNAs whereas with direct repeat configuration, a large truncation was less
      frequent. Most integration events analysed in this study could be addressed by
      previously proposed models; however, the characteristics of the T-DNA repeats and
      the complicated filler DNA between two T-DNA copies imply that multiple
      mechanisms are involved in the formation of T-DNA repeats as well as in T-DNA
      integration in plants.

PMID- 22980201
TI  - Long-term response of tomato plants to changing nutrient concentration in the
      root environment-the role of proline as an indicator of sensory fruit quality.
AB  - The aim of the trial was to investigate the time course of changes in content of
      proline and organic compounds affecting sensory quality of ripe red tomatoes
      after nutrient concentration had been changed. Tomato (Lycopersicon esculentum
      Mill. cv. Counter) plants were grown in nutrient solutions containing equal
      nutrient ratios at either low or high concentration (N1=standard solution; N2=5.5
      times the standard concentration). Immediately after first harvest of ripe
      tomatoes, half of the plants of each treatment were transferred to nutrient
      solutions of higher (from N1 to N2) or lower (from N2 to N1) nutrient
      concentration. Proline content in leaves of plants transferred to higher or lower
      nutrient concentration adjusted to control levels (N2 and N1, respectively)
      within 2 weeks. Growing and ripe fruit reached the corresponding control levels
      within the same time or 1-5 weeks later. Similar time courses were observed for
      sugar concentration and titratable acidity in fruit. Apart from leaves, proline
      content of young growing fruit also increased with increasing radiation intensity
      at high nutrient concentration. However, in ripe fruit, proline content increased
      only with low to moderate radiation intensity and decreased when a certain stress
      level was exceeded. Similar results were found for osmolality and sugar
      concentration of ripe fruit, while titratable acidity remained rather unaffected
      by radiation. The role of proline as an indicator of sensory fruit quality is
      discussed.

PMID- 22980202
TI  - Isolation and characterization of class A4 heat shock transcription factor from
      alfalfa.
AB  - Plant heat shock transcription factors (HSFs) regulate transcription of heat
      shock (HS) genes. In Arabidopsis thaliana, 21 HSFs have been classified into
      groups A-C. Members of class A act as typical transcriptional activators, whereas
      B HSFs function as coactivators or repressors depending on promoter context. The
      function of class C HSFs is still unclear. Here, we present the isolation and
      characterization of the first HSF from alfalfa (Medicago sativa L.) and designate
      it MsHSFA4 based on amino acid sequence analysis. The MsHSFA4 gene was determined
      to be single copy and was detected at two separate genetic loci in the tetraploid
      Medicago sativa. Overexpression of MsHSFA4 in tobacco mesophyll protoplasts
      resulted in weak transcriptional activity, similar to that exhibited by
      Arabidopsis AtHSFA4a. The MsHSFA4 proximal promoter contains three putative HSE
      elements, and the gene itself is activated both by heat and cold stress.

PMID- 22980203
TI  - Changes of purine and pyrimidine nucleotide biosynthesis during shoot initiation
      from epicotyl explants of white spruce (Picea glauca).
AB  - Nucleotide metabolism was investigated during white spruce organogenesis by
      following the metabolic fate of (14)C-labeled adenine, adenosine and inosine, as
      purine precursors, and orotic acid, uridine, and uracil, as pyrimidine
      intermediates. Key enzymes of purine and pyrimidine metabolism were also assayed
      during the organogenic process. White spruce epicotyl explants cultured on shoot
      forming (SF) medium had a better ability to utilize adenine and adenosine for
      nucleotide and nucleic acid synthesis, compared to tissue cultured on non-shoot
      forming (NSF) medium. High levels of salvage products were observed in SF tissue
      after 10 days in culture, when shoot formation was initiated along the epicotyl
      axis of the explants. Such a differential utilization of purine precursors was
      mainly due to the higher specific activity of the two adenine and adenosine
      salvage enzymes, adenine phosphoribosyltransferase (APRT) and adenosine kinase
      (AK), measured in SF tissue. Similar catabolism of inosine was observed in both
      SF and NSF conditions during the 30 days of culture. For pyrimidines, the higher
      activities of the de novo, salvage, and degradation pathways observed in SF
      tissue, compared to NSF tissue throughout the course of the experiment, clearly
      denote a faster turnover of pyrimidine nucleotides in the former. Taken together,
      these results suggest that a better utilization of purine bases and nucleosides
      for nucleotide and nucleic acid synthesis, as well as a more rapid turnover of
      pyrimidine nucleotides, represent a physiological switch, which occurs during the
      initiation and continuation of the organogenic process in white spruce.

PMID- 22980204
TI  - Stable male sterility induced by the expression of mutated melon ethylene
      receptor genes in Nicotiana tabacum.
AB  - A major concern about genetically modified crops is transgene flow through pollen
      dispersal. We previously demonstrated that overexpression of the mutated melon
      ethylene receptor genes Cm-ETR1/H69A or Cm-ERS1/H70A induces pollen abortion and
      altered flower architecture, resulting in sterility or reduced fertility in
      transgenic tobacco plants. To investigate the stability of these traits, three
      transgenic tobacco lines in which Cm-ETR1/H69A or Cm-ERS1/H70A confer sterility
      or reduced fertility were grown in a greenhouse with environmental conditions
      that changed, depending on the outside conditions. During the growth of the
      plants, the temperature ranged from 31 degrees C at the beginning of September to
      17 degrees C at the beginning of November. The light provided was natural
      sunlight. The first group of plants flowered in late September, and the second
      group flowered in late October. The wild-type plants showed the homostyly type of
      floral architecture, whereas, three transgenic lines showed the heterostyly type.
      The floral architecture was stable during the different flowering periods. Pollen
      production was significantly reduced in two transgenic lines and completely
      aborted in one transgenic line, and these traits were also stable during the
      different flowering periods. These results suggest that the sterility or reduced
      fertility induced by the expression of mutated melon ethylene receptor genes in
      transgenic tobacco plants is stable under varying environmental conditions.

PMID- 22980205
TI  - Enzymes of tyrosine catabolism in Arabidopsis thaliana.
AB  - Tyrosine catabolism is an essential pathway in animals, but its role in plants is
      unclear. The first steps of tyrosine degradation lead to the formation of
      homogentisate. In animals this is then sequentially acted on by homogentisate
      dioxygenase (HGO), maleylacetoacetate isomerase (MAAI) and fumarylacetoacetate
      hydrolase (FAH) to generate fumarate and acetoacetate. In plants, homogentisate
      is used to generate the essential redox metabolites tocopherol and plastoquinone,
      which effectively act as an alternative metabolic fate for tyrosine. Having
      determined that a zeta class glutathione transferase from Arabidopsis thaliana is
      a functional MAAI, we have looked for evidence that the mammalian degradation
      pathway could also operate in plants. Based on array and quantitative PCR
      experiments, the A. thaliana homologues AtHGO, AtMAAI and AtFAH could be shown to
      be expressed, with AtHGO and AtMAAI showing evidence of co-regulation. cDNAs
      encoding AtHGO, AtMAAI and AtFAH were cloned in Escherichia coli and shown to
      represent a fully functional catabolic pathway when combined in vitro. The
      significance of this pathway, including increased transcription of the associated
      enzymes in senescing tissue, compartmentalisation and impact on flux into
      synthesis of Vitamin E and other tocopherols of biotechnological interest is
      discussed.

PMID- 22980206
TI  - New gene construction strategy in T-DNA vector to enhance expression level of
      sweet potato sporamin and insect resistance in transgenic Brassica oleracea.
AB  - Sporamin, an abundant storage protein in tuberous roots of sweet potato,
      possesses strong inhibitory activity against trypsin and pest-resistance. To
      promote consistent high-level expression of sporamin and insect resistance in
      transgenic Brassica plants, a wound-responsive sporamin promoter (Pspoa) alone or
      combined with matrix-attached-region-like DNA segment (spoMAR) were constructed
      for driving sporamin cDNA. The results showed the transgenic plants containing
      Pspoa-drived sporamin and spoMAR displayed the highest level and low inter
      transformant variability of sporamin expression, and the ability of insect
      resistance of transformants positively correlated with sporamin activity.
      Furthermore, expressions of Pspoa-drived sporamin especially combined with the
      spoaMAR retains high and steady levels in the T(1) and T(2) generations, in
      marked contrast to the variable expression patterns observed in CaMV35S promoter
      driven transformants. This study evidently indicates that the Pspoa and spoaMAR
      would be very efficient for high transgene expression in plants and obtaining
      inherently stable transformants in consecutive progenies.

PMID- 22980207
TI  - Efficient delivery of small interfering RNA to plant cells by a nanosecond pulsed
      laser-induced stress wave for posttranscriptional gene silencing.
AB  - Small interfering RNA (siRNA) induced posttranscriptional gene silencing (PTGS)
      has been an efficient method for genetic and molecular analysis of certain
      developmental and physiological processes and represented a potential strategy
      for both controlling virus replication and developing therapeutic products.
      However, there are limitations for the methods currently used to deliver siRNA
      into cells. We report here, to our knowledge, the first efficient delivery of
      siRNA to plant cells by a nanosecond pulsed laser-induced stress wave (LISW) for
      posttranscriptional gene silencing. Using LISW, we are able to silence gene
      expression in cell cultures of three different plant species rice (Oryza sativa
      L.), cotton (Gossypium hirsutum L.), and slash pine (Pinus elliottii Engelm.).
      Gene silencing induced by siRNA has been confirmed by northern blot, laser
      scanning microscopy, and siRNA analysis. These data suggested that LISW-mediated
      siRNA delivery can be a reliable and effective method for inducing PTGS in
      cultured cells.

PMID- 22980208
TI  - Protective role of antioxidant enzymes under high temperature stress.
AB  - An experiment was conducted to study the effect of high temperature stress on the
      antioxidant enzyme activity in five wheat genotypes viz., PBW 343, PBW 175, HDR
      77, HD 2815 and HD 2865. There was significant increase in the activity of
      superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) in the
      late and very late planting and at all stages of plant growth, i.e., vegetative,
      anthesis and 15 days after anthesis (DAA), however glutathione reductase (GR) and
      peroxidase (POX) activity decreased under late and very late plantings compared
      to normal planting. In general HD 2815, HDR-77 showed relatively higher SOD, APX,
      GR, CAT and POX activity in the late plantings compared to PBW 343, PBW 175 and
      HD 2865. Significant reduction in chlorophyll content and increase in membrane
      injury index were observed in all genotypes with age, and also under late and
      very late sowings at all the stages of plant growth. However HD 2815 and HDR-77,
      which showed highest activity of various antioxidant enzymes under late and very
      late sowing also showed minimum reduction in chlorophyll content and lower
      membrane injury index, indicating the amelioration of high temperature stress
      induced oxidative stress by antioxidant enzymes. Various antioxidant enzymes
      showed positive correlation (r) with chlorophyll content and negative with
      membrane injury index at most of the stages in the five wheat genotypes.

PMID- 22980209
TI  - Tolerance of photosynthesis to photoinhibition, high temperature and drought
      stress in flag leaves of wheat: A comparison between a hybridization line and its
      parents grown under field conditions.
AB  - Photosynthesis and its tolerance to photoinhibition, high temperature and drought
      stress of flag leaves were investigated in a wheat (Triticum aestivum L.)
      hybridization line (1-12) and its parents (Jing-411 and Xiaoyan-54). From the
      beginning of flowering to the 10th day, light-saturated CO(2) assimilation rate
      (P(max)) showed no significant decrease and P(max) of 1-12 was comparable to that
      of its parents. From the 20th day, P(max) decreased significantly and this
      decrease was much less in 1-12 than in its parents, whereas no decrease in
      chlorophyll content was observed in 1-12 and its parents on the 20th day,
      indicating that photo-oxidative damage occurred in 1-12 and its parents but 1-12
      is more resistant to photo-oxidative damage than its parents. To further
      characterize photo-oxidative damage, tolerance to photoinhibition, high
      temperature and drought stress was compared in 1-12 and its parents. When exposed
      to high light (1400MUmolm(-2)s(-1)), the maximal efficiency of PSII
      photochemistry (F(v)/F(m)) decreased significantly with increasing exposure time
      and such a decrease was much less in 1-12 than in its parents. When exposed to
      higher temperatures (30-45 degrees C) for 15min, F(v)/F(m) started to decrease at
      42 degrees C in 1-12 and its parents. The greatest decrease in F(v)/F(m) was
      observed in Jing-411. 1-12 and Xiaoyan-54 showed a comparable decrease in
      F(v)/F(m). Similar results were also observed in the actual PSII efficiency
      (Phi(PSII)), photochemical quenching (q(P)) and non-photochemical quenching
      (q(N)). During exposure of detached leaves to air under room temperature
      conditions, relative water content decreased with increasing exposure time.
      However, such a decrease was greatest in Jing-411 followed by Xiaoyan-54, and 1
      12. There were neither changes in F(v)/F(m) nor q(N) during water loss in the
      line and its parents. However, there was a decrease in Phi(PSII) and q(P) and
      greatest decrease was observed in Jing-411 followed by Xiaoyan-54, and 1-12.
      Also, the decrease in P(max) was greatest in Jing-411, followed by Xiaoyan-54,
      and 1-12 during water loss. In addition, the activities of ribulose-1,5
      bisphosphate carboxylase, phosphoenolpyruvate carboxylase, pyruvate phosphate
      dikinase, NADP-malate dehydrogenase and NADP-malate enzyme were significantly
      higher in 1-12 than in its parents. The results in this study suggest that high
      resistance to photo-oxidative damage of the flag leaves in 1-12 may be the
      physiological basis for its high yield when grown in north China. Our results
      also suggest that parents can be selected for improved biochemical and
      physiological traits and crossed to high yielding agronomically elite materials
      which can be selected for higher performance in yield.

PMID- 22980210
TI  - Differential regulation of Lehsp23.8 in tomato plants: Analysis of a multiple
      stress-inducible promoter.
AB  - Small heat shock proteins (sHSPs) are the major family of HSP induced by heat
      stress in plants. In this report, an approximately 1.9kb of Lehsp23.8 5'-flanking
      sequence was isolated from tomato genome. By using the beta-glucuronidase (GUS)
      reporter gene system, the developmental and tissue specific expression of the gus
      gene controlled by the Lehsp23.8 promoter was characterized in transgenic tomato
      plants. Strong GUS staining was detected in the roots, leaves, flowers, fruits
      and germinated seeds after heat shock. The heat-induced GUS activity was
      different in the floral tissues at various developmental stages. Fluorometric GUS
      assay showed that the heat-induced GUS activity was higher in the pericarp than
      in the placenta, and it was the lowest in the locular gel. The heat-shock
      induction of the Lehsp23.8 promoter depended on the different stages of fruit
      development. The optimal heat-shock temperatures leading to the maximal GUS
      activity in the pericarp of green, breaker, pink and red fruits were 42, 36, 39
      and 39 degrees C, respectively. The heat-induced GUS activity in tomato fruits
      increased gradually within 48h of treatment and weakened during tomato fruit
      ripening. Obvious GUS activities under cold, exogenous ABA and heavy metal
      (Cd(2+), Cu(2+), Pb(2+) or Zn(2+)) stress conditions were also detected. These
      results show that the Lehsp23.8 promoter is characterized as strongly heat
      inducible and multiple-stress responsive.

PMID- 22980211
TI  - RETRACTED: Production of transgenic orchardgrass via Agrobacterium-mediated
      transformation of seed-derived callus tissues.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the Authors. The editors would like to confirm the
      retraction of this paper, at the request of the authors, for an unintentional
      duplication of Figure 2B that was used in a previous publication without
      attribution, and which did not show the data it claimed to show: S.-H. Lee, D.-G.
      Lee, H.-S. Woo and B.-H. Lee, Development of transgenic tall fescue plants from
      mature seed-derived callus via Agrobacterium-mediated transformation. Asian
      Austral. J. Anim. Sci., 17 (2004) 1390-1394.

PMID- 22980212
TI  - ETR1-, JAR1- and PAD2-dependent signaling pathways are involved in C6-aldehyde
      induced defense responses of Arabidopsis.
AB  - C6-aldehydes [(E)-2-hexenal and (Z)-3-hexenal] induce expression of defense
      genes, accumulation of antifungal substances, and resistance against Botrytis
      cinerea with Arabidopsis. In order to elucidate the signaling pathway mediating
      the defense responses induced by C6-aldehydes in Arabidopsis, we compared the
      responses of Arabidopsis mutants deficient in the signaling pathways; i.e., etr1
      1 (ethylene resistant), jar1-1 (jasmonate resistant), npr1-1 (salicylic acid
      insensitive), or pad2-1 (phytoalexin-deficient) with those of wild type (WT)
      plants. Induction of some, but not all of the defense genes in response to C6
      aldehydes was significantly repressed in jar1-1, etr1-1, and pad2-1, but not at
      all in npr1-1. C6-aldehyde-treatment enhanced accumulation of camalexin with WT
      and npr1-1, but only partially with etr1-1 and jar1-1. pad2-1 showed little
      accumulation of camalexin. npr1-1 accumulated the antifungal substances as WT
      did, however, etr1-1, jar1-1 and pad2-1 exhibited only partial accumulation. The
      treatment enhanced resistance of etr1-1, jar1-1 and npr1-1 against B. cinerea,
      but failed to enhance the resistance of pad2-1. Taken together, it was suggested
      that ETR1-, JAR1-, and PAD2-dependent signaling pathways were simultaneously
      activated by C6-aldehyde-treatment. Among these, PAD2-dependent signaling
      appeared to be most important. In contrast, involvement of NPR1-dependent
      signaling was minimal.

PMID- 22980213
TI  - The origin and evolution of sweet potato (Ipomoea batatas Lam.) and its wild
      relatives through the cytogenetic approaches.
AB  - The distribution and organization of 5S and 18S-5.8S-26S (18S) rDNA were studied
      in 10 varieties of hexaploid Ipomoea batatas, five accessions of tetraploid
      Ipomeoa trifida, and six related species (five diploids, I. trifida, I. triloba,
      I. tiliacea, I. leucantha and I. setosa and one tetraploid, I. tabascana), by
      using fluorescence in situ hybridization (FISH). The FISH data obtained indicated
      that polyploidization was followed by decrease in the number of 18S rDNA loci in
      higher ploidy level and provided evidence for major genomic rearrangements and/or
      diploidization in polyploid I. batatas. Among the five diploid species examined,
      I. trifida appeared to be the most closely related to I. batatas. By contrast, I.
      leucantha was closed to I. tiliacea, but both species were distant from sweet
      potato. I. triloba and I. setosa were distantly related to the rest of Ipomoea
      batatas complex. The close relationship between I. trifida and I. batatas was
      also demonstrated by the presence of one 18S and CMA marker in these two
      chromosome complements only. Based on chromosome morphology, tetraploid I.
      trifida appeared to be more closely related to sweet potato than I. tabascana.
      Taking all data obtained in this study, I. trifida might be the progenitor of I.
      batatas, and I. tabascana, interspecific hybrid between these two species.

PMID- 22980214
TI  - Causality and sex roles: prejudice against patterns? A reply to Ah-King.

PMID- 22980215
TI  - Neurobiological correlates of sociality, mate choice and learning.

PMID- 22980216
TI  - Liver perfusion CT during hepatic arteriography for the hepatocellular carcinoma:
      dose reduction and quantitative evaluation for normal- and ultralow-dose
      protocol.
AB  - OBJECTIVES: The purpose of this study was to investigate whether substantial
      reduction of the computed tomography (CT) dose is possible in liver CT perfusion
      imaging by comparing the results of ultralow-dose CT perfusion imaging with those
      of conventional CT perfusion imaging the same patients and under the same
      conditions. MATERIALS AND METHODS: The study was composed following two parts:
      computer simulation and patients study. In computer simulation, noise was added
      to the images so that the standard deviation (SD) of the CT values in the liver
      parenchyma became various values using ImageJ. Time density curves (TDCs) were
      created from the simulated data, and the influence of difference in the SDs on
      the shapes of the TDCs was investigated. In the patient study, CT perfusion
      during intra-arterial injection was performed in 30 consecutive patients
      undergoing transcatheter arterial chemoembolization. CT perfusion images were
      acquired twice, at 100 mA (CTDI(vol), 300 mGy) for normal and at 20 mA
      (CTDI(vol), 60 mGy) for the ultralow radiation doses, under the same conditions.
      RESULTS: No change was observed in the shape of the TDCs and peak values in the
      analysis of simulation images. A very good correlation was observed between the
      normal- and ultralow-dose CT images for all analyzed values (R(2)=0.9885 for
      blood flow, 0.9269 for blood volume, and 0.8424 for mean transit time).
      CONCLUSIONS: Our results demonstrated that there was no significant difference in
      the analysis results of perfusion CT between ultralow-dose CT performed using 20%
      of the conventional dose and normal-dose CT perfusion.

PMID- 22980217
TI  - Minutissamides E-L, antiproliferative cyclic lipodecapeptides from the cultured
      freshwater cyanobacterium cf. Anabaena sp.
AB  - The extract of UIC 10035, a strain obtained from a sample collected near the town
      of Homestead, South Florida, showed antiproliferative activity against MDA-MB-435
      cells. Bioassay-guided fractionation led to the isolation of a series of cyclic
      lipodecapeptides, named minutissamides E-L (1-8). The planar structures were
      determined by analysis of HRESIMS, tandem MS, and 1D and 2D NMR data, and the
      stereoconfigurations were assigned by LC-MS analysis of the Marfey's derivatives
      after acid hydrolysis. Minutissamides E-L (1-8) exhibited antiproliferative
      activity against MDA-MB-435 cells with IC(50) values ranging between 1 and 10
      MUM. The structures of minutissamides E-L (1-8) were closely related with those
      of the previously reported lipopeptides, puwainaphycins A-E and minutissamides A
      D, characterized by the presence of a lipophilic beta-amino acid and three non
      standard amino acids NMeAsn, OMeThr and Dhb (alpha,beta-dehydro-alpha
      aminobutyric acid). The strain UIC 10035 was designated as cf. Anabaena sp. on
      the basis of morphological and 16S rRNA gene sequence analyses.

PMID- 22980218
TI  - Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR
      activity.
AB  - Cancerous inhibitor of PP2A (CIP2A) is a novel human oncoprotein that inhibits
      PP2A, contributing to tumor aggressiveness in various cancers. Several studies
      have shown that downregulation of CIP2A by small molecules reduces PP2A-dependent
      phosphorylation of Akt and induces cell death. Here, a series of mono- and di
      substituted quinazoline and pyrimidine derivatives based on the skeleton of
      erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against
      hepatocellular carcinoma were evaluated. The di-substituted quinazoline and
      pyrimidine derivatives were more potent inhibitors of cancer-cell proliferation
      than the mono-substituted derivatives. In particular, compound 1 with chloride at
      position 2 of quinazoline was as potent as erlotinib in inducing cell death but
      no inhibition for EGFR activity. Further assays confirmed a correlation between
      cell death, and CIP2A and Akt inhibition by these derivatives. Among all the
      derivatives, compounds 19 and 22 showed the most potent antiproliferative
      activities and the strongest inhibition of CIP2A and p-Akt expression.

PMID- 22980219
TI  - Design and synthesis of pyrrolo[3,2-d]pyrimidine HER2/EGFR dual inhibitors:
      improvement of the physicochemical and pharmacokinetic profiles for potent in
      vivo anti-tumor efficacy.
AB  - During the course of our studies on a novel HER2/EGFR dual inhibitor (TAK-285),
      we found an alternative potent pyrrolo[3,2-d]pyrimidine compound (1a). To enhance
      the pharmacokinetic (PK) profile of this compound, we conducted chemical
      modifications into its N-5 side chain and conversion of the chemically modified
      compounds into their salts. Among them, 2cb, the tosylate salt of compound 2c,
      showed potent HER2/EGFR kinase inhibitory activity (IC(50): 11/11 nM) and
      cellular growth inhibitory activity (BT-474 cell GI(50): 56 nM) with a good drug
      metabolism and PK (DMPK) profile. Furthermore, 2cb exhibited significant in vivo
      antitumor efficacy in both mouse and rat xenograft models with transplanted 4-1ST
      gastric cancer cell lines (mouse, T/C=0%, 2cb po bid at 100 mg/kg; rat, T/C: -1%,
      2cb po bid at 25 mg/kg).

PMID- 22980220
TI  - The bench scientist's guide to statistical analysis of RNA-Seq data.
AB  - BACKGROUND: RNA sequencing (RNA-Seq) is emerging as a highly accurate method to
      quantify transcript abundance. However, analyses of the large data sets obtained
      by sequencing the entire transcriptome of organisms have generally been performed
      by bioinformatics specialists. Here we provide a step-by-step guide and outline a
      strategy using currently available statistical tools that results in a
      conservative list of differentially expressed genes. We also discuss potential
      sources of error in RNA-Seq analysis that could alter interpretation of global
      changes in gene expression. FINDINGS: When comparing statistical tools, the
      negative binomial distribution-based methods, edgeR and DESeq, respectively
      identified 11,995 and 11,317 differentially expressed genes from an RNA-seq
      dataset generated from soybean leaf tissue grown in elevated O3. However, the
      number of genes in common between these two methods was only 10,535, resulting in
      2,242 genes determined to be differentially expressed by only one method. Upon
      analysis of the non-significant genes, several limitations of these analytic
      tools were revealed, including evidence for overly stringent parameters for
      determining statistical significance of differentially expressed genes as well as
      increased type II error for high abundance transcripts. CONCLUSIONS: Because of
      the high variability between methods for determining differential expression of
      RNA-Seq data, we suggest using several bioinformatics tools, as outlined here, to
      ensure that a conservative list of differentially expressed genes is obtained. We
      also conclude that despite these analytical limitations, RNA-Seq provides highly
      accurate transcript abundance quantification that is comparable to qRT-PCR.

PMID- 22980221
TI  - Floating glenoid after reverse total shoulder arthroplasty: a case report.

PMID- 22980222
TI  - Acromial vascularized graft pedicled on the acromial branch of the
      thoracoacromial trunk for treatment of clavicular pseudoarthrosis.

PMID- 22980223
TI  - Platelet count and serum thrombopoietin level as predictors for morbidity and/or
      mortality in thrombocytopenic neonates.
AB  - BACKGROUND: Serum thrombopoietin in thrombocytopenic infants is largely related
      to the cause of thrombocytopenia and the underlying disease. Many perinatal
      factors can affect thrombopoietin level. PATIENTS AND METHODS: A prospective
      cross-sectional study  on 119 thrombocytopenic neonates: 54 full term and 65
      preterm had been conducted. Thrombopoietin assay was done using a qualitative
      enzyme-linked immunosorbent assay technique. The test was repeated on the change
      of clinical status (recovery or deterioration). RESULTS: Lowering  of
      thrombopoietin level was noted on reversal of platelet count to normal (P<0.001).
      Survival is significantly related to platelet count in full term (P = 0.04), but
      insignificant among thrombocytopenic preterms. Platelet count is negatively
      correlated to thrombopoietin  level in neonates both in full term and preterm (r
      = -0.59, -0.69, respectively, P<0.001). Platelet count was found to be the best
      predictor for duration of recovery of thrombocytopenia in neonates compared with
      other factors including thrombopoietin  level. CONCLUSION: Thrombocytopenic
      neonates had high levels of thrombopoietin. Despite the high thrombopoietin level
      in neonates died with severe thrombocytopenia, yet, mortality is related to the
      cause and outcome of thrombocytopenia rather than the serum thrombopoietin 
      level. It is recommended to diagnose and treat the underlying cause of
      thrombocytopenia rather than to generalize the therapy based on thrombopoietin
      level.

PMID- 22980224
TI  - Doubly labeled water validation of a computerized use-of-time recall in active
      young people.
AB  - OBJECTIVE: Low levels of daily energy expenditure (insufficient physical activity
      and increased sedentary time) have been associated with adverse health outcomes
      in young people. The Multimedia Activity Recall for Children and Adolescents
      (MARCA) is a computerized, self-report, use-of-time tool that can assess daily
      energy expenditure. The study aim was to validate the MARCA for the estimation of
      energy expenditure in young people, using the criterion standard doubly labeled
      water. MATERIALS/METHODS: Over a 15 day assessment period, 32 participants (10-18
      years) completed the MARCA and underwent a doubly labeled water protocol.
      Indirect calorimetry was used to assess resting metabolic rate. Total daily
      energy expenditure (TEE) and activity-related energy expenditure (AEE) were
      estimated from both the MARCA and doubly labeled water. Association and agreement
      between methods for TEE and AEE were assessed using Spearman correlations and
      Bland-Altman plots, respectively. RESULTS: Compared to doubly labeled water, the
      MARCA over-estimated TEE by an average of 50 kcal/day (limits of agreement -1 589
      to 1 490 kcal/day) and under-estimated AEE 105 kcal/day (limits of agreement -1
      404 to 1 614 kcal/day). The MARCA showed strong correlation with doubly labeled
      water for TEE (rho=0.70, p<0.0001) and moderate correlation for AEE (rho=0.56,
      p=0.0009). CONCLUSIONS: Overall, the MARCA indicated moderate validity for the
      assessment of daily TEE and AEE. The wide limits of agreement indicate the MARCA
      has greater utility for group-level rather than individual-level estimates.

PMID- 22980225
TI  - Effects of ATF4 on PGC1alpha expression in brown adipose tissue and metabolic
      responses to cold stress.
AB  - OBJECTIVE: We have shown previously that the expression of peroxisome
      proliferator activated receptor gamma coactivator (PGC1alpha) increases
      significantly in the white and brown adipose tissue of activating transcription
      factor 4 (ATF4) global knockout mice, which suggests that ATF4 is involved in the
      regulation of PGC1alpha expression. The goal of the current study is to
      investigate this possibility and elucidate the underlying cellular mechanisms.
      MATERIAL/METHODS: The effects of ATF4 on PGC1alpha expression and on PGC1alpha
      promoter activity were analyzed in vivo and in vitro using mice, HIB-1B, and 293T
      cell line. The physiological functions of ATF4 in the regulation of PGC1alpha
      expression were confirmed by analysis of body temperature of Atf4(-/-) and
      Atf4(+/+) mice in response to cold stress as well as expression of Complex I, II,
      III, V in BAT. RESULTS: In this study, we showed ATF4 to be a negative regulator
      of PGC1alpha expression through competitive binding with cAMP response element
      binding protein (CREB) at a cAMP response element (CRE) site in the PGC1alpha
      promoter. ATF4 was also found to influence the expression of mitochondria-related
      proteins, including Complex I, II, III, and IV through regulation of PGC1alpha.
      Finally, we showed that Atf4(-/-) mice have higher core body temperatures in
      reduced-temperature environments than control mice. CONCLUSION: This study
      describes the mechanisms underlying ATF4 regulating PGC1alpha expression. We
      demonstrate a novel function of ATF4 in the regulation of thermogenesis. Taken
      together, these observations provide new insight into the physiological functions
      of ATF4, especially the regulation of thermogenesis and the response to cold
      stress.

PMID- 22980226
TI  - Regional cerebral blood flow differences in patients with mild cognitive
      impairment between those who did and did not develop Alzheimer's disease.
AB  - Mild cognitive impairment (MCI) is a heterogeneous condition associated with
      increased risk of Alzheimer's disease (AD) and other dementias. This study aimed
      to identify areas of initial hypoperfusion in MCI conversion to AD using
      technetium (Tc-99m) hexamethylpropyleneamine oxime (TC-99m HMPAO) single photon
      emission computed tomography (SPECT) to compare baseline cerebral hypoperfusion
      in converted MCI and non-converted MCI patients and normal controls. Forty-nine
      MCI patients were recruited for brain magnetic resonance imaging (MRI), detailed
      neuropsychological testing, Tc-99m HMPAO SPECT, and 1- to 2-year periodic follow
      up to monitor progression to dementia status. We processed SPECT images with
      Statistical Parametric Mapping 8 (SPM8) software and performed voxel-based
      statistical parametric mapping analysis. Thirty-nine of 49 MCI patients were
      included in our analysis. Nine patients were diagnosed with conversion to AD, on
      average 19.0+/-6.6 months after initial assessment. Compared with normal
      controls, converted MCI patients demonstrated perfusion deficits in both
      parahippocampal gyri and right precuneus, and non-converted MCI patients
      demonstrated hypoperfusion in the left parahippocampal gyrus. Compared with non
      converted MCI patients, converted MCI patients demonstrated significant
      hypoperfusion in both cingulate gyri and right precuneus. Our study suggests that
      using brain SPECT to identify initial hypoperfusion in patients with MCI may be
      helpful for predicting MCI patients likely to develop AD.

PMID- 22980227
TI  - Fever of unknown origin (FUO) due to systemic lupus erythematosus (SLE)
      presenting as pericarditis.
AB  - Fevers of unknown origin (FUOs) are classified according to the underlying
      disorder. The 4 main clinical categories of FUOs are infectious, malignant,
      rheumatic/inflammatory, and miscellaneous disorders. Although malignancy remains
      the most common cause of FUOs, rheumatic/inflammatory disorders remain important
      diagnostically and therapeutically. Rheumatic/inflammatory disorders, for
      example, systemic lupus erythematosus (SLE) presenting as FUO, have become
      uncommon in recent years because of better serologic diagnostic tests. However,
      SLE remains a rare but important cause of FUO in adults. SLE may be a difficult
      FUO diagnosis when a patient presents with fever without joint manifestations as
      the only symptoms of SLE. During the workup of the patient described in this
      article, the other causes of pericarditis were ruled out and SLE pericarditis was
      diagnosed. This is a rare case of an adult FUO with pericarditis as the only
      manifestation of SLE.

PMID- 22980228
TI  - Unravelling barriers to accessing HIV prevention services experienced by African
      and Caribbean communities in Canada: lessons from Toronto.
AB  - Barriers to accessing HIV-prevention services, experienced by African and
      Caribbean communities in Canada, is an issue warranting sustained research. This
      study seeks to achieve a better understanding of the nature of HIV-prevention
      services in Canada, and to explore the dynamics, which underpin barriers to
      accessing these services confronting African and Caribbean populations in Toronto
      (Canada). This study also endeavours to assess what is being done to reduce these
      barriers. Semi-structured qualitative interviews with 7 professionals and
      community workers who were involved in organizing, researching and delivering HIV
      prevention services were conducted for this study. Four themes pertaining to
      barriers to accessing HIV-prevention services, including, levels of cultural
      competence and sensitivity among service providers; cultural and social stigma
      directed at persons living with HIV/AIDS; various social determinants of health,
      including gender, race and precarious immigration status'; as well as constrained
      funding resources that are available for service providers; were uncovered in the
      findings of the study. The paper concludes that several health promotion and
      health education initiatives exist, which can help reduce these barriers to HIV
      prevention service access for these populations. However, in order to ensure
      their effectiveness there will be much needed involvement from community and
      other relevant government agencies, which will need to work separately and in
      conjunction with one another, in order to tackle some of the broader issues that
      affect these populations.

PMID- 22980230
TI  - Termination of pregnancy in Curacao: need for improvement of sexual and
      reproductive healthcare.
AB  - BACKGROUND: In Curacao Termination of Pregnancy (TOP) is still forbidden by law,
      although a policy of tolerance has been stipulated since 1999. This paper is
      about the prevalence of TOP and about its health complications. These data on TOP
      are officially unknown but are suspected to be rather high. METHODS: One year
      registration of illegal performed termination of pregnancy cases by all general
      physicians (GPs) practicing TOP in Curacao. The registration included patient
      characteristics according to the model of the National Abortion Registration in
      The Netherlands, adjusted to the local Curacao situation. Socio demographic
      characteristics, number of previous pregnancies and TOPs, pregnancy duration,
      contraception methods and reason for failure were registered. The comparative
      part of the research compares TOP rates of Curacao with those of Antillean women
      in the Netherlands. The gynaecologists in the referral hospital registered
      complications requiring hospital admission after TOP. RESULTS: All GPs performing
      TOP participated and the majority registered extensively. The total number of
      registered TOP was 1126. 666 of the 1126 were registered using the local adjusted
      Abortion Registration Model. With 30.000 women aged between 15 and 45 living in
      Curacao, the TOP rate was at least 38 (per 1000 in that age category), comparable
      to rates for Antillean women in the Netherlands. Mean age was 26.9 years. Nearly
      half (47%) had one or more TOPs before; the majority (53%) was less than 7 weeks
      pregnant and two third (67%) had one or more children. Two third of the women did
      not use contraception (63%). For those using contraception, main reason for
      failure was inconsistent use (50%). There were 14 hospital admissions due to
      complications of TOP. CONCLUSION: The number of TOP is high in Curacao and
      comparable to (first generation) Antillean women living abroad in the
      Netherlands. Most unintended pregnancies originated from no or inconsistent use
      of reliable contraception. Improvement of sex education is necessary in order to
      bring down the number of TOP, as well as realizing accessible and affordable
      contraception, including sterilization. The number of complications around TOPs
      was equal to other countries where TOP is illegal.

PMID- 22980229
TI  - Determinants of the utilization of diversified types of professionals for mental
      health reasons in a Montreal (Canadian) catchment area.
AB  - The study was designed to identify factors associated with the diversity of
      professionals consulted by 212 individuals affected by at least one mental
      disorder in the past 12 months in a Montreal catchment area. For inclusion in the
      study, participants had to be aged 15 to 65 and reside in the study zone. A
      comprehensive set of variables were analyzed in accordance with the Andersen's
      behavioural model of health service use. General practitioners, psychiatrists,
      and psychologists were the main professionals consulted in this study. Having
      post-secondary education, more than a single mental disorder, excellent
      relationships with neighbours, and (marginally) being a lifelong victim of
      violence were associated with higher numbers of professionals consulted. As this
      study highlights the large number of diversified professionals consulted for
      reason of mental disorders, shared care initiatives may prove beneficial. Greater
      effort could also be made in increasing services toward those deemed more
      vulnerable.

PMID- 22980231
TI  - Depressive symptoms and bone mineral density among police officers in a
      northeastern US City.
AB  - PURPOSE: The purpose of this study was to examine the association between
      depressive symptoms and bone mineral density (BMD). METHODS: Depressive symptoms
      were measured using the Center for Epidemiologic Studies Depression (CES-D)
      scale. BMD of total hip, femoral neck, anterio-posterior (AP) spine, wrist, and
      total body were measured by DXA using standardized procedures. Mean levels of BMD
      across gender-specific tertiles of CES-D score were obtained using ANOVA and
      ANCOVA. RESULTS: Participants included 97 police officers (41 women; 29-64
      years). Depressive symptoms were not associated with BMD at any site among men.
      However among women, mean BMD values decreased across increasing (worsening)
      tertiles of CES-D for the AP spine (low CES-D=1.22 +/- 0.04; medium CES-D=1.05+/
      0.04; high CES-D=1.03+/-0.04 g/cm2; p=0.035) and for the whole body (low=1.26+/
      0.03; medium=1.20+/-0.03; high=1.11+/-0.03 g/cm2; p=0.018) after adjustment.
      CONCLUSIONS: Higher depressive symptoms were associated with lower BMD among
      female but not male officers.

PMID- 22980233
TI  - Use of risk assessment tool for inpatient traumatic intracranial hemorrhage after
      falls in acute care hospital setting.
AB  - Severe injuries such as intracranial hemorrhage (ICH) are the most serious
      problem after falls in hospital, but they have not been considered in risk
      assessment scores for falls. We tried to determine the risk factors for ICH after
      falls in 20,320 inpatients (696,364 patient-days) aged from 40 to 90 years who
      were admitted to a tertiary-care university hospital. Possible risk factors
      including STRATIFY risk score for falls and FRAXTM risk score for fractures were
      analyzed by univariate and multivariate analyses. Fallers accounted for 3.2% of
      the patients, and 5.0% of the fallers suffered major injuries, including
      peripheral bone fracture (59.6%) and ICH (23.4%). In addition to STRATIFY, FRAXTM
      was significantly associated not only with bone fractures but also ICH.
      Concomitant use of risk score for falls and risk score for fractures might be
      useful for the prediction of major injuries such as ICH after falls.

PMID- 22980232
TI  - ST elevation: telling pathology from the benign patterns.
AB  - Benefits of early reperfusion in patients presenting with acute ST elevation
      myocardial infarction (STEMI) are well known. The American College of Cardiology
      / American Heart Association guidelines recommend triage decisions are made
      within 10 minutes of performing initial electrocardiogram (ECG). Since many
      patients presenting with ischemic symptoms may have ST elevation (STE) at
      baseline, not all STE signify transmural ischemia. Benign patterns can be easy to
      find in some cases. However, patients with benign STE at baseline (left
      ventricular hypertrophy, early repolarization pattern) may have ongoing ischemia
      and present with Non-ST elevation myocardial infarction (NSTEMI) or even STEMI
      superimposed on the benign pattern. The ability of clinicians to distinguish
      between ischemic and non ischemic STE varies widely and is affected by prevalence
      of such changes in patient population. More studies need to be done to delineate
      the criteria to clearly distinguish between ischemic and non ischemic ST
      elevation.

PMID- 22980235
TI  - Young adults' perceptions on life prospects and gender roles as important factors
      to influence health behaviour: a qualitative study from Karachi, Pakistan.
AB  - The purpose of this qualitative study was to explore perceptions and expectations
      of young males and females, in Karachi, Pakistan, regarding their life prospects
      and gender roles, with resulting implications for health behaviour. The main
      theme emerging was "Young adults' prospects in life are hampered by psychosocial
      and gender equality constraints". Gender inequality and the low status of women
      in society were described as major obstacles to the overall development.
      Persistent withholding of information to the younger generation on sexual and
      reproductive health issues was perceived to increase exposure to health risks,
      particularly sexually transmitted infections (STIs). The present study reveals
      new discourses on equality among young adults, pointing towards an increasing,
      sound interaction between the sexes and aspirations for more gender equal
      relationships. Such views and awareness among the younger generation constitutes
      a strong force towards change of traditional norms, including reproductive health
      behaviour, and calls for policy change.

PMID- 22980239
TI  - Bacteriological monitoring and sustainable management of beach water quality in
      Malaysia: problems and prospects.
AB  - Despite the growing demand of tourism in Malaysia, there are no resolute efforts
      to develop beaches as tourist destinations. With no incentives to monitor public
      beaches or to use them in a sustainable manner, they might eventually degenerate
      in quality as a result of influx of pollutants. This calls for concerted action
      plans with a view to promoting their sustainable use. The success of such plans
      is inevitably anchored on the availability of robust quality monitoring schemes.
      Although significant efforts have been channelled to collation and public
      disclosure of bacteriological quality data of rivers, beach water monitoring
      appears left out. This partly explains the dearth of published information
      related to beach water quality data. As part of an on-going nation-wide
      surveillance study on the bacteriological quality of recreational beaches, this
      paper draws on a situation analysis with a view to proffering recommendations
      that could be adapted for ensuring better beach water quality in Malaysia.

PMID- 22980238
TI  - Violence against women living with HIV: a cross sectional study in Nepal.
AB  - BACKGROUND: Violence against Women (VAW) and Human Immunodeficiency Virus (HIV)
      both constitute major public health issues and there is an increasing evidence of
      their intersection. Data are sparse on the intersection of VAW and HIV in South
      Asia region. We aimed to identify different forms and magnitude of violence
      incurred by women living with HIV, and analyse causes and consequences. METHODS:
      A cross-sectional study was conducted among 43 HIV positive women in three
      districts of Nepal, in the period of March-May 2008. Data was collected through
      semi-structured interview questionnaire. RESULTS: The vast majority of the
      participants (93.02%) had suffered from at least one form of the violence. The
      prevalence of violence rose up sharply after being diagnosed with HIV positive
      than before (93.02% vs.53.5%). Forty-five percent of the participants reported
      their husbands being main perpetrator of violence. Self-humiliation and health
      and treatment problem were the major consequences of violence as reported by 90%
      and 77.5% of the participants respectively. CONCLUSION: Violence was observed to
      be highly prevalent among women living with HIV in Nepal. Further larger and
      nationally representative researches are imperative to better understand the
      cross-section between VAW and HIV. Our finding recommends to prioritizing
      programs on social aspects of HIV such as violence.

PMID- 22980240
TI  - Self-care behaviors among Thai primigravida teenagers.
AB  - The purpose of this study was to investigate predictive factors of the self-care
      behaviors among Thai teenagers with primigravida. The samples of 206 primigravida
      teenagers attending ANC clinics of six hospitals in the North-Eastern region of
      Thailand were included. Data collection was done through self administered
      questionnaire. Scales of the questionnaire had reliability coefficients ranging
      from 0.72 - 0.92. The data were analyzed by using descriptive and inferential
      statistics. The results revealed that the percentage-mean score of overall self
      care behavior was 76.91. The percentage-mean scores of self-care behaviors in
      specific trimester were found that the score in the second trimester was lower
      than the scores in the first and third trimesters (57.58, 60.45, and 64.65,
      respectively). Factors associated with overall self-care behavior were perceived
      self-efficacy, perceived social support from family, knowledge on self-care
      during pregnancy, accessibility to health services, self-esteem and age (r =
      0.47, 0.34, 0.28, 0.24, 0.19, and 0.15, respectively). Perceived self-efficacy
      and knowledge on self-care during pregnancy were the two considerable predictors
      accounted for 25% of the variance in the self-care behaviors of Thai teenagers
      with primigravida.

PMID- 22980237
TI  - Factors associated with the household income of persons living with HIV/AIDS in
      China.
AB  - This study provides a profile of 866 people living with HIV/AIDS (PLWHA) in three
      provinces in rural China and identifies factors associated with per-capita income
      in AIDS-affected households. The majority of the participants were female,
      married, had completed primary school, and were 30-49 years of age. Thirty
      percent of respondents lived in a household with at least one other HIV/AIDS
      patient and 15% had experienced the death of a household member due to HIV/AIDS.
      Therefore, health professionals should be aware of issues of grief and caregiver
      burnout among rural PLWHA and their families. Three-quarters of the respondents
      continued to work after being diagnosed with HIV/AIDS. Household per capita
      income was significantly higher for married individuals and those still working.
      Possible government and workplace policy initiatives that endeavor to increase
      income and mitigate the economic impact of HIV/AIDS on households are discussed.

PMID- 22980236
TI  - Can an accelerometer-based monitor be used to accurately assess physical activity
      in a population of survivors of critical illness?
AB  - PURPOSE: To investigate the validity and reliability of the Activity Monitoring
      Pod (AMP331) to record gait parameters in  healthy young adults (YA) and
      intensive care unit inpatients (ICU). METHODS: Fifteen YA completed a series of
      over-ground walks. Another 15 YA completed a series of treadmill walks. The ICU
      group (N=20) completed a series of over-ground walks with repeat trials. Gait
      parameters were recorded simultaneously for each walk. RESULTS: For the YA over
      ground condition, no significant differences were found between the measures
      recorded by the systems. For the YA treadmill condition, 43% of the measures
      differed (P < .05). For the ICU group, the AMP331 underestimated distance and
      speed by 3m and 25cm/s respectively. Reliability measures for distance (ICC 0.99,
      95%CI 0.98 - 0.99) and step count (ICC 0.99, 95%CI 0.99 - 1.00) were excellent.
      CONCLUSIONS: The AMP 331 is a valid instrument for recording basic gait
      parameters for over-ground walking in healthy YA and ICU survivors.

PMID- 22980243
TI  - Traditional arabic & islamic medicine: a conceptual model for clinicians and
      researchers.
AB  - Eighty percent of the population in the developing world relies on traditional
      medicine, and 70-80% of the population in developed countries utilized
      complementary therapies. Though a vibrant healing tradition pervades modern life
      in the Arab and Muslim world, no clear definition or model exists to organize
      it's multiple and intertwined elements . We define Traditional Arabic and Islamic
      Medicine (TAIM) as a system of healing practiced since antiquity in the Arab
      world within the context of religious influences of Islam and comprised of
      medicinal herbs, dietary practices, mind-body therapy, spiritual healing and
      applied therapy whereby many of these elements reflect an enduring
      interconnectivity between Islamic medical and prophetic influences as well as
      regional healing practices emerging from specific geographical and cultural
      origins. Our definition and conceptual model represents a novel addition to the
      literature on Arab and Muslim health practices, and presents an opportunity to
      address a global health concern.

PMID- 22980242
TI  - Profile of modifiable and non-modifiable risk factors in stroke in a rural based
      tertiary care hospital - a case control study.
AB  - BACKGROUND: Stroke, a major public health problem in India and worldwide, is
      associated with many risk factors. The modification of risk factors, an important
      public health strategy, has been shown to reduce the risk of stroke. Hence the
      present study was carried out to document the risk factor profile of stroke.
      METHODS: It was a case-control study. Patients with stroke admitted in a tertiary
      care centre in central India and age and sex matched controls were included.
      Detail history and clinical examination was done in all cases and controls. The
      risk factors studied were education, socioeconomic status (according to
      Kuppuswamy's classification), level of physical activity, alcohol intake, and
      smoking, tobacco chewing, family history of stroke and history of systemic
      hypertension, transient ischemic attack or ischemic heart disease. Anthropometric
      (weight, height, body mass index and waist circumference) measurements were done
      in all patients. Electrocardiogram was done in cases as well as controls and
      abnormalities noted. STATISTICAL ANALYSIS: The data was analyzed using Epi info
      version 3.4.1 software. Chi-square test was used as test of significance and p
      value less than 0.05 was considered as significant. RESULTS: On comparing the
      cases with controls, sedentary life-style (p=0.02), history of transient ischemic
      attack (p=0.002), coronary artery disease (p=0.014), family history of stroke
      (p=0.001), systemic hypertension (p<0.001) and ECG abnormalities (p=0.04) were
      significant risk factors whereas low socio-economic status (p=0.40), smoking
      (p=0.12), tobacco chewing (p=0.35), alcohol consumption (p=0.22), obesity [both
      central and generalized as assessed by waist circumference (p=0.33) and BMI
      respectively (p=0.43)] and Diabetes mellitus (p=0.07) were not found to be
      statistically significant risk factors. The most significant risk factor was
      systemic hypertension (OR= 15.92, 95% CI, 1.78-6.85) followed by coronary artery
      disease (OR=3.86, 95% CI, 1.13-14.50), abnormal ECG (OR=2.49, 95% CI, 0.97-6.96)
      and sedentary life-style (OR=2.41, 95% CI, 1.07-5.49). CONCLUSIONS: In the
      present hospital based case control study in patients with stroke, sedentary life
      style, history of transient ischemic attack, family history of stroke, coronary
      artery disease, systemic hypertension and abnormal ECG were significant risk
      factors. This could be helpful in early identification of subjects at risk for
      stroke and formulating public health strategy, if proven by larger population
      based studies.

PMID- 22980241
TI  - Pattern of skin diseases at university of Benin teaching hospital, Benin city,
      Edo State, South-South Nigeria: a 12 month prospective study.
AB  - BACKGROUND AND OBJECTIVE: This study aims to look at the pattern and incidence of
      skin diseases seen in Dermatology/Venereology clinic at the University of Benin
      Teaching Hospital, Benin City, Edo State, South-South Zone, Nigeria and compare
      it with other zones of Nigeria. MATERIALS AND METHODS: This was a prospective
      study on pattern and incidence of skin diseases in new patients presenting at the
      Dermatology/ Venereology outpatient clinic of the University of Benin Teaching
      Hospital, Benin City, Edo State, South-South, Nigeria, from September 2006 to
      August 2007. All patients were seen by the researchers. Diagnosis were made
      clinically and sometimes with the support of histopathology. RESULTS: A total
      number of 4786 patients were seen during the study period and these comprised
      2647 HIV/AIDS patients and 2112 pure Dermatological patients. Out of 4786
      patients, 755 (15.8%) were new patients. The new patients comprised 96 (12.7%)
      children patients (< 15 years) and 659 (83.7%) adult patients (>15years). The
      ages of the patients ranged from 2 weeks to 80 years and more than two-third were
      < 40 years. There were 354 males (46.9%) and 401 females (53.1%). This represents
      female: male ratio of 1.1: 1. Eczematous dermatitis accounted for 20.9% of the
      skin diseases and was the most common of the skin diseases observed. This is
      consistent with observation from other zones in Nigeria. Other skin diseases
      observed in order of frequencies include: Papulosqamous disorder (9.0%),
      Infectious skin diseases like fungal, viral, bacterial and parasitic infestation,
      at 7.9%, 7.7%, 2.3% and 2.1% respectively. Pigmentary disorders (5.0%), hair
      disorders (4.2%) and Benign neoplastic skin disease (6.5%). All the patients that
      had neurofibromatosis were females (1.9%). HIV-related skin diseases were
      observed to have increased remarkably (7.9%) with Kaposi's sarcoma, papular
      pruritic eruptions and drug eruptions being the commonest mode of presentation.
      CONCLUSION: The current pattern of skin diseases in Benin City, South-South
      Nigeria seems to follow a similar pattern observed in other Geo-political zones
      in Nigeria. The eczematous dermatitis took the lead and the impact of HIV-related
      skin diseases were vividly noticed to be on the increase. Connective tissue
      disorder and cutaneous malignancies were low in their occurrences. Our findings
      showed no major differences in the pattern of skin diseases when compared with
      other zones of Nigeria. Allergic skin diseases were observed to be on the
      increase in all the geo-political zones; possibly due to increase in urbanization
      and its attending socio-economic burden.

PMID- 22980245
TI  - Comparison of the acute physiology and chronic health evaluation score (APACHE)
      II with GCS in predicting hospital mortality of neurosurgical intensive care unit
      patients.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS) is popular, simple, and reliable, and
      provides information about the level of consciousness in trauma patients.
      However, a systemic evaluation scale specially in patients with multiple trauma
      is so important. The revised Acute Physiology and Chronic Health Evaluation
      system type 2 (APACHE II) is a physiologically based system including
      physiological variables. This study compares the efficacy of the predicting power
      for mortality and functional outcome of GCS and APACHEII in patients with
      multiple trauma in intensive care unit. METHODS: This study included the patients
      with head injury associated with systemic trauma admitted in the ICU of Shahid
      Rajaee Hospital in 2007 and 2008. Sensitivity, specificity and correct prediction
      of outcome by GCS and APACHE II were assessed and compared. RESULTS: This study
      included 93 patients (79 males, 14 females; mean age 60.5; range 14 to 87 years)
      with head injury associated with systemic trauma in 2007 and 2008. Mortality
      increased in the elderly group. The mean survival score using APACHE II was 36.5
      and death score was 67.4 . These values using GCS were 10.3 and 6.8,
      respectively. CONCLUSION: For the assessment of mortality, the GCS score still
      provides simple, less-time consuming and effective information concerning head
      injury patients, especially in emergencies; however, for the prediction of
      mortality in patients with multiple trauma. APACHE II is superior to GCS since it
      includes the main physiologic parameters of patients.

PMID- 22980244
TI  - Perception and experience regarding menopause among menopaused women attending
      teaching hospitals in Erbil City.
AB  - BACKGROUND AND OBJECTIVES: The timing of menopause, perception as well as
      menopausal symptoms varies between populations and within populations. The main
      objective of the present study was to assess women's perception and experience
      regarding menopause, to find out symptoms and mean age of menopause and to study
      socio-demographic characteristics of menopaused women and to find out its
      relationship with their age at menopause and their knowledge about menopause.
      METHODS: Over a period of eight months a descriptive cross sectional study were
      carried out at the outpatient departments of four teaching hospitals in Erbil
      city. A total of 500 menopaused women their age ranged from 40-60 years were
      interviewed using a close ended self administered questionnaire. RESULTS: Mean
      age of menopause was 47.44 years with median age was 48 years, 4.4% had premature
      menopause and 23.6% had early menopause. The only factors that significantly
      associated with age at menopause were education and pattern of menstrual
      cessation and 93.4% of menopaused women were heard about menopause, 56.6% had
      prior knowledge of menopausal symptoms, cessation of menstruation was positive in
      47.0% and 85.8% of women perceive menopause as natural condition and the most
      common menopausal symptoms were tiredness occurring in 83.2%. CONCLUSION: Most of
      menopaused women perceive menopause as natural condition and not aware about
      hormone replacement therapy and the mean age of menopause is comparable to that
      mean reported in other part of Iraq. Among menopaused women tiredness was the
      most common complaint was followed by hot flushes and night sweats.

PMID- 22980246
TI  - XJP-1 protects endothelial cells from oxidized low-density lipoprotein-induced
      apoptosis by inhibiting NADPH oxidase subunit expression and modulating the
      PI3K/Akt/eNOS pathway.
AB  - Endothelial apoptosis triggered by oxidized low-density lipoprotein (ox-LDL) can
      accelerate the progression of endothelial dysfunction in atherosclerosis. (+/
      )7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP-1) is a natural phenolic compound
      derived from banana peel. In the present study, we investigated the anti
      apoptotic effect of XJP-1 in human umbilical vein endothelial cells (HUVECs)
      exposed to ox-LDL and explored underlying mechanisms. Our results showed that in
      the presence of ox-LDL, XJP-1 significantly attenuated ox-LDL-mediated
      cytotoxicity, apoptosis, caspase-3 activation, reactive oxygen species (ROS)
      generation, and NADPH oxidase subunit (p22phox and p47phox) expression in HUVECs.
      In addition, the anticytotoxic and anti-apoptotic effect of XJP-1 was partially
      inhibited by a PI3K inhibitor (LY294002), an Akt inhibitor (SH-6), a specific
      eNOS inhibitor (l-NAME) and a NADPH oxidase inhibitor (DPI). In exploring the
      underlying mechanisms of XJP-1 action, we found that XJP-1 eliminated ox-LDL
      induced dephosphorylation of Akt and eNOS in a dose-dependent manner. However,
      XJP-1 alone upregulation of Akt and eNOS phosphorylation were blocked by LY294002
      and SH-6. Moreover, XJP-1 increased NO production, but this effect was abolished
      by LY294002, SH-6 and l-NAME. The inhibition of ox-LDL-induced endothelial
      dysfunction by XJP-1 is due at least in part to its anti-oxidant activity and its
      ability to modulate the PI3K/Akt/eNOS signaling pathway.

PMID- 22980247
TI  - A patient with dementia: decision-making capacity and surrogate decision makers.

PMID- 22980248
TI  - Free skin cancer screening provides access to care.

PMID- 22980234
TI  - Seafood consumption and components for health.
AB  - In recent years, in developed countries and around the world, lifestyle-related
      diseases have become a serious problem. Numerous epidemiological studies and
      clinical trials have demonstrated that diet is one of the major factors that
      influences susceptibility to lifestyle-related diseases, especially the middle
      senile state. Studies examining dietary habits have revealed the health benefits
      of seafood consumption. Seafood contains functional components that are not
      present in terrestrial organisms. These components include n-3-polyunsaturated
      fatty acids, such as eicosapentaenoic acid and docosahexsaenoic acid, which aid
      in the prevention of arteriosclerotic and thrombotic disease. In addition,
      seafood is a superior source of various nutrients, such as protein, amino acids,
      fiber, vitamins, and minerals. This review focuses on the components derived from
      seafood and examines the significant role they play in the maintenance and
      promotion of health.

PMID- 22980249
TI  - Squamous cell carcinomas in Afro-Caribbean women.

PMID- 22980250
TI  - Leadership versus management training in residency programs.

PMID- 22980251
TI  - Cutaneous aspergillosis mimicking pancreatic and gouty panniculitis.

PMID- 22980252
TI  - Systemic complications of levamisole toxicity.

PMID- 22980253
TI  - Nomenclature proposal on laser ablation and nonablation.

PMID- 22980255
TI  - The effects of isotretinoin on wisdom tooth extraction.

PMID- 22980256
TI  - Melkersson-Rosenthal syndrome: a possible association with psoriasis.

PMID- 22980257
TI  - Congenital hypertrichotic melanoneurocytoma: a congenital hypertrichotic plaque
      with overlapping neural and nevoid features.

PMID- 22980258
TI  - Congenital melanocytic nevi: where are we now? Part I. Clinical presentation,
      epidemiology, pathogenesis, histology, malignant transformation, and
      neurocutaneous melanosis.
AB  - Congenital melanocytic nevi (CMN) are present at birth or arise during the first
      few weeks of life. They are quite common, may have a heritable component, and can
      present with marked differences in size, shape, color, and location. Histologic
      and dermatoscopic findings may help suggest the diagnosis, but they are not
      entirely specific. CMN are categorized based on size, and larger lesions can have
      a significant psychosocial impact and other complications. They are associated
      with a variety of dermatologic lesions, ranging from benign to malignant. The
      risk of malignant transformation varies, with larger CMN carrying a significantly
      higher risk of malignant melanoma (MM), although with an absolute risk that is
      lower than is commonly believed. They may also be associated with neuromelanosis,
      which may be of greater concern than cutaneous MM. The information presented
      herein aims to help dermatologists determine when it is prudent to obtain a
      biopsy specimen or excise these lesions, to obtain radiographic imaging, and to
      involve other specialists (eg, psychiatrists and neurologists) in the patient's
      care.

PMID- 22980259
TI  - Congenital melanocytic nevi: where are we now? Part II. Treatment options and
      approach to treatment.
AB  - Treatment of congenital melanocytic nevi (CMN) is generally undertaken for 2
      reasons: (1) to reduce the chances of cutaneous malignant melanoma and (2) for
      cosmetic reasons. Over the past century, a large number of treatments for CMN
      have been described in the literature. These include excision, dermabrasion,
      curettage, chemical peels, radiation therapy, cryotherapy, electrosurgery, and
      lasers. Only low-level evidence supporting these approaches is available, and
      large randomized controlled trials have not been published. This article explores
      therapeutic controversies and makes recommendations based on the best available
      evidence.

PMID- 22980262
TI  - Generalized idiopathic neutrophilic eccrine hidradenitis in a 7-month-old child.

PMID- 22980263
TI  - Photodynamic therapy with intralesional photosensitizer and laser beam
      application: an alternative treatment for nodular basal cell carcinoma.

PMID- 22980264
TI  - A case of eosinophilic pustular folliculitis with response to infliximab.

PMID- 22980265
TI  - Giant cell fibroblastoma mimicking a soft fibroma arising within a
      dermatofibrosarcoma protuberans.

PMID- 22980266
TI  - Axillary Fox-Fordyce-like disease induced by laser hair removal therapy.

PMID- 22980267
TI  - Clinical variability of shiitake dermatitis.

PMID- 22980268
TI  - Intravesical mitomycin C-induced generalized pustular folliculitis.

PMID- 22980269
TI  - Chemical burn from topical apple cider vinegar.

PMID- 22980270
TI  - Dermatoscopy of pigmented extramammary Paget disease simulating melanoma.

PMID- 22980271
TI  - Leukemia labialis: a rare presentation of leukemia cutis limited to the lips.

PMID- 22980272
TI  - Mycosis fungoides following skin trauma.

PMID- 22980273
TI  - Plantar pustulosis during rituximab therapy for rheumatoid arthritis.

PMID- 22980274
TI  - Development of linear IgA bullous dermatosis in a patient with psoriasis taking
      ustekinumab.

PMID- 22980275
TI  - Pityriasis lichenoides et varioliformis acuta associated with subcutaneous
      immunoglobulin administration.

PMID- 22980276
TI  - Necrotic ulcerations on the back of the hands in a patient with chronic renal
      failure: an uncommon presentation of calciphylaxis.

PMID- 22980277
TI  - Lichen planus pemphigoides in a 2-year-old girl: response to treatment with
      methotrexate.

PMID- 22980278
TI  - Sweat gland carcinoma versus metastatic breast carcinoma: a continued struggle
      among clinicians and dermatopathologists.

PMID- 22980279
TI  - Nasal-type extranodal natural killer/T-cell lymphoma presenting as genital
      ulcers.

PMID- 22980280
TI  - Skin involvement in ALK-negative systemic anaplastic large-cell lymphoma.

PMID- 22980281
TI  - Metastatic cystic nodule of rectal SCC with basaloid features mimicking a BCC of
      the face.

PMID- 22980282
TI  - Isolated cutaneous extramedullary relapse of leukemia confirmed by fluorescent in
      situ hybridization analysis.

PMID- 22980283
TI  - Palisaded neutrophilic and granulomatous dermatitis in an adolescent girl with
      perinuclear antineutrophil cytoplasmic antibody-positive pauci-immune
      glomerulonephritis and arthritis.

PMID- 22980284
TI  - Wells syndrome in a child triggered by parvovirus B19 infection?

PMID- 22980285
TI  - Autoantibodies to nuclear matrix protein 2/MJ in adult-onset dermatomyositis with
      severe calcinosis.

PMID- 22980286
TI  - Giant nevus lipomatosus cutaneous superficialis with intramuscular lipomatosis.

PMID- 22980287
TI  - Nickel allergy and dermatitis following use of a laptop computer.

PMID- 22980288
TI  - Micro-structural characterisation of homogeneous and layered MFC nano-composites.
AB  - The complementary capabilities of various characterisation methods for micro
      structural assessment are demonstrated. The assessed structures were composed of
      unbleached microfibrillated cellulose (MFC) in combination with bleached and
      2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) pre-treated MFC materials. The
      biodegradable nano-composites were thus characterised in detail, including laser
      profilometry, scanning electron microscopy (SEM) in high and low vacuum modes,
      and field-emission SEM. The distribution of the unbleached MFC materials was
      assessed by staining the unbleached MFC with osmium tetroxide (OsO(4)), which
      reacts with C=C double bonds encountered in lignin. In addition, some properties
      of the MFC nano-composite films were tested, i.e. tensile properties, water
      wettability and oxygen permeability. In general, the group of characteristics of
      the nano-composite MFC films was better than the properties of the films made of
      the neat MFC qualities. This indicates that mixing complementary MFC qualities
      could give synergetic effects that are not exploited completely when using the
      MFC qualities separately. The study thus confirms the suitability of unbleached
      MFC materials as a component in multilayer structures, for example biodegradable
      packaging applications.

PMID- 22980289
TI  - SINGLE-01: a randomized, controlled trial comparing the efficacy and depth of
      insertion of single- and double-balloon enteroscopy by using a novel method to
      determine insertion depth.
AB  - BACKGROUND: Single-balloon enteroscopy (SBE) was introduced as an alternative to
      double-balloon enteroscopy (DBE) for the investigation and management of small
      bowel conditions. To date, there is only 1 randomized, controlled trial comparing
      SBE and DBE in a Western population. OBJECTIVE: To compare the 2 instruments in a
      Western population to assess for differences in clinical outcomes and insertion
      depth (ID). A novel method to determine ID by counting folds on withdrawal was
      used. DESIGN: Multicenter, randomized, controlled trial. SETTING: University
      hospitals in Melbourne and Sydney, Australia. PATIENTS: Patients with suspected
      or proven small-bowel disease. INTERVENTIONS: SBE and DBE. MAIN OUTCOME
      MEASUREMENT: The primary endpoint was diagnostic yield (DY). Secondary endpoints
      were therapeutic yield (TY), procedure times, and ID. An intention-to-treat
      analysis was performed. RESULTS: A total of 116 patients were screened, and 107
      patients were enrolled between July 2008 and June 2010, in whom 119 procedures
      were undertaken (53 SBEs and 66 DBEs). DY was 57% for SBE and 53% for DBE (P =
      .697). TY was 32% for SBE and 26% for DBE (P = .490). The median enteroscopy
      times were identical for SBE and DBE at 60 minutes. The mean ID by the fold
      counting method for antegrade procedures was 201.1 folds for SBE and 258.6 folds
      for DBE (P = .046). After multiple comparisons adjustment, this difference did
      not reach statistical significance. Mean IDs by using the visual estimation
      method for SBE and DBE were, respectively, 72.1 cm and 75.2 cm (P = .835) for
      retrograde procedures and 203.8 cm and 234.1 cm (P = .176) for antegrade
      procedures. LIMITATIONS: Unable to reach target sample size, mostly single-center
      recruitment, novel method to determine ID, which requires further validation.
      CONCLUSIONS: SBE has DY, TY, and procedure times similar to those of DBE. There
      were no statistically significant differences in ID between SBE and DBE. By using
      the fold-counting method for antegrade procedures, the estimated IDs for SBE and
      DBE were 201.1 folds versus 258.6 folds (P = .046; P = not significant after
      adjustment for multiple comparisons). ( CLINICAL TRIAL REGISTRATION NUMBER:
      ACTRN12609000917235.).

PMID- 22980290
TI  - Diagnostic performance of two confocal endomicroscopy systems in detecting
      Barrett's dysplasia: a pilot study using a novel bioprobe in ex vivo tissue.
AB  - BACKGROUND: There are currently 2 existing confocal laser endomicroscopy (CLE)
      platforms: probe-based CLE (pCLE) and endoscope-based CLE (eCLE) systems, each
      with its own criteria for identifying dysplasia in Barrett's esophagus (BE). The
      diagnostic performance of these 2 systems has not been directly compared. DESIGN:
      Preclinical, feasibility study. OBJECTIVES: We compared the interrater agreement
      and diagnostic performance of the pCLE and eCLE systems. In addition, we
      evaluated a new BE endomicroscopy criteria based on fluorescent glucose intensity
      uptake. PATIENTS: Thirteen patients with Barrett's esophagus and high-grade
      dysplasia or early cancer undergoing 16 EMR. INTERVENTION: CLE imaging was
      performed using two different probes with 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4
      yl)amino]-2-deoxyglucose, a fluorescent glucose analog with preferential uptake
      in dysplastic mucosa to supply contrast. Four quadrants were imaged per specimen
      with a total of 64 imaged mucosal sites presented to three gastroenterologists.
      MAIN OUTCOME MEASUREMENTS: Interobserver agreement and accuracy for dysplasia was
      assessed of images classified according to Miami criteria, stacked eCLE images
      classified using the Mainz criteria and a novel fluorescence intensity criteria.
      RESULTS: The interrater agreements were 0.17, 0.68, and 0.87 for the Miami,
      Mainz, and the fluorescence intensity criteria, respectively. Overall accuracy in
      detecting dysplasia was 37% (95% CI, 30.3-43.9), 44.3% (95% CI, 37.3-50.9), and
      78.6% (95% CI, 72.2-83.3) for the Miami, Mainz, and the fluorescence intensity
      criteria, respectively. LIMITATIONS: This imaging technique and proposed
      fluorescence intensity criteria using 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4
      yl)amino]-2-deoxyglucose in EMR tissue will require in vivo validation and cannot
      be directly used with the current eCLE and pCLE clinical applications.
      CONCLUSIONS: In this preclinical feasibility study, the use of an eCLE system
      with a topical fluorescent contrast in ex vivo EMR tissue demonstrated higher
      interrater agreement and accuracy.

PMID- 22980291
TI  - Identification of suitable endogenous control genes for microRNA expression
      profiling of childhood medulloblastoma and human neural stem cells.
AB  - BACKGROUND: Medulloblastoma (MB) is the most common type of malignant childhood
      brain tumour. Although deregulated microRNA (miRNA) expression has been linked to
      MB pathogenesis, the selection of appropriate candidate endogenous control (EC)
      reference genes for MB miRNA expression profiling studies has not been
      systematically addressed. In this study we utilised reverse transcriptase
      quantitative PCR (RT-qPCR) to identify the most appropriate EC reference genes
      for the accurate normalisation of miRNA expression data in primary human MB
      specimens and neural stem cells. RESULTS: Expression profiling of 662 miRNAs and
      six small nuclear/ nucleolar RNAs in primary human MB specimens, two CD133+
      neural stem cell (NSC) populations and two CD133- neural progenitor cell (NPC)
      populations was performed using TaqMan low-density array (TLDA) cards. Minimal
      intra-card variability for candidate EC reference gene replicates was observed,
      however significant inter-card variability was identified between replicates
      present on both TLDA cards A and B. A panel of 18 potentially suitable EC
      reference genes was identified for the normalisation of miRNA expression on TLDA
      cards. These candidates were not significantly differentially expressed between
      CD133+ NSCs/ CD133- NPCs and primary MB specimens. Of the six sn/snoRNA EC
      reference genes recommended by the manufacturer, only RNU44 was uniformly
      expressed between primary MB specimens and CD133+ NSC/CD133- NPC populations (P =
      0.709; FC = 1.02). The suitability of candidate EC reference genes was assessed
      using geNorm and NormFinder software, with hsa-miR-301a and hsa-miR-339-5p found
      to be the most uniformly expressed EC reference genes on TLDA card A and hsa-miR
      425* and RNU24 for TLDA card B. CONCLUSIONS: A panel of 18 potential EC reference
      genes that were not significantly differentially expressed between CD133+ NSCs/
      CD133- NPCs and primary human MB specimens was identified. The top ranked EC
      reference genes described here should be validated in a larger cohort of
      specimens to verify their utility as controls for the normalisation of RT-qPCR
      data generated in MB miRNA expression studies. Importantly, inter-card
      variability observed between replicates of certain candidate EC reference genes
      has major implications for the accurate normalisation of miRNA expression data
      obtained using the miRNA TLDA platform.

PMID- 22980292
TI  - Use of alternative methodologies for evaluation of composite end points in trials
      of therapies for critical limb ischemia.

PMID- 22980293
TI  - Rationale and design of the first randomized, double-blind, placebo-controlled
      trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal
      Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial).
AB  - BACKGROUND: Stem cell therapy is an emerging treatment modality in cardiovascular
      disease. The best cell type and delivery method in different cardiovascular
      diseases remain to be determined. STUDY DESIGN: The MSC-HF trial is a phase 2,
      single-center, double-blind, randomized, placebo-controlled trial of
      intramyocardial delivery of autologous bone-marrow derived mesenchymal stromal
      cells (MSCs) in patients with chronic ischemic heart failure. A total of 60
      patients will be randomized in a 2:1 pattern to receive intramyocardial
      injections of either MSCs or placebo. Patients will be followed up for 12 months.
      METHODS: Bone marrow will be obtained by aspiration from the iliac crest.
      Mesenchymal stromal cells will be isolated, and culture will be expanded for 6 to
      8 weeks. A total of 12 to 15 MSC or placebo injections will be placed in an
      ischemic viable region of the myocardium using the electromechanical NOGA-XP
      system (Biologics Delivery Systems Group, Johnson & Johnson, Irwindale, CA).
      ENDPOINTS: The primary endpoint is change in left ventricle end-systolic volume,
      measured by magnetic resonance imaging (MRI) or computed tomography (CT) at 6
      month follow-up. Secondary endpoints are left ventricle ejection fraction,
      ventricular volumes, wall thickness, and systolic wall thickening measured by MRI
      or CT in addition to measurement of myocardial scar tissue by MRI. Other
      secondary endpoints are safety of treatment, clinical symptoms and functional
      capacity, weekly angina attacks, use of short-term nitroglycerine, and quality of
      life. CONCLUSION: A randomized, double-blind, placebo-controlled, clinical trial
      of intramyocardial delivery of MSCs in patients with ischemic heart failure has
      been set up to confirm the positive findings in open-labeled clinical trials.

PMID- 22980294
TI  - A proposal for new clinical concepts in the management of atrial fibrillation.
AB  - Atrial fibrillation (AF) represents a growing public health burden. It is a
      complex condition, involving a number of etiologic factors and arrhythmia
      mechanisms associated with atrial remodeling. Greater understanding of these
      mechanisms may improve therapy. Current AF classification schemes are limited by
      simplicity. A number of risk factors predict AF onset, and additional factors are
      being evaluated in registry studies. Doppler imaging and Holter monitoring in
      high-risk patients to predict the onset of AF and progression from paroxysmal to
      permanent AF are promising. There is a need for a novel multifactorial
      classification model encompassing AF duration, symptoms, markers of atrial
      remodeling, and a risk score for AF onset, persistence, progression, and
      complications to guide treatment and prognostication. Preventing AF onset with
      upstream therapy is of great interest, but current data are conflicting. More
      study is needed to optimize rhythm control with antiarrhythmic drugs and targeted
      ablation to specific patient populations at an earlier stage. There is little
      consensus on optimal rate control and no information relating to optimum rate
      control in specific populations. This article highlights new concepts in AF and
      directions for future research.

PMID- 22980295
TI  - Implications of geographical variation on clinical outcomes of cardiovascular
      trials.
AB  - Cardiovascular clinical trials are increasingly conducted globally as a means to
      reduce costs, expedite timelines, provide broad applicability, and satisfy
      regulatory authorities. Potential problems with trial globalization include
      regional differences in patient characteristics, medical practice patterns, and
      health policies which may influence outcomes and limit generalizability.
      Moreover, concerns have been raised about ethical misconduct and unsatisfactory
      quality oversight in regions with less trial experience and infrastructure. This
      article reviews geographical differences in cardiovascular trials in heart
      failure, acute coronary syndromes, hypertension and atrial fibrillation. It also
      explores potential explanations for these differences and methods to standardize
      the presentation of trial results. This review is based on discussions between
      basic scientists and clinical trialists at the 8th Global Cardio Vascular
      Clinical Trialists Forum 2011 in Paris, France, from December 2 to 3.

PMID- 22980296
TI  - Preferences of people with advanced heart failure-a structured narrative
      literature review to inform decision making in the palliative care setting.
AB  - BACKGROUND AND APPROACH: There is a growing emphasis on the need for high-quality
      and patient-centered palliative care for patients with heart failure (HF) near
      end of life. Accordingly, clinicians require adequate knowledge of patient values
      and preferences, but this topic has been underreported in the HF literature. In
      response, we conducted a structured narrative review of available evidence
      regarding patient preferences for HF care near end of life, focusing on
      circumstances of death, advance care planning, and preferences for specific HF
      therapies. RESULTS: Patients had widely varying preferences for sudden
      ("unaware") death versus a death that was anticipated ("aware"), which would
      allow time to make arrangements and time with family; preferences influenced
      their choice of HF therapies. Patients and physicians rarely discussed advance
      care planning; physicians were rarely aware of resuscitation preferences. Advance
      care planning discussions rarely included preferences for limiting implantable
      cardioverter defibrillator use, and patients were often uninformed of the option
      of implantable cardioverter defibrillator deactivation. A substantial minority of
      patients strongly preferred improved quality of life versus extended survival,
      but preferences of individuals could not be easily predicted. CONCLUSIONS:
      Current evidence regarding preferences of patients with HF near end of life
      suggests substantial opportunities for improvement of end-of-life HF care. Most
      notably, the wide distribution of patient preferences highlights the need to
      tailor approach to patient wishes, avoiding assumptions of patient wishes. A
      research agenda and implications for health care provider training are proposed.

PMID- 22980297
TI  - A gender-specific blood-based gene expression score for assessing obstructive
      coronary artery disease in nondiabetic patients: results of the Personalized Risk
      Evaluation and Diagnosis in the Coronary Tree (PREDICT) trial.
AB  - BACKGROUND: Currently available noninvasive tests to risk stratify patients for
      obstructive coronary disease result in many unnecessary cardiac catheterizations,
      especially in women. We sought to compare the diagnostic accuracy of presenting
      symptoms, noninvasive test results, and a gene expression score (GES) in
      identifying obstructive coronary artery disease (CAD) according to gender, using
      quantitative coronary angiography as the criterion standard. METHODS: The PREDICT
      trial is a prospective multicenter observational study designed to develop and
      validate gene expression algorithms to assess obstructive CAD, defined as at
      least one >=50% diameter stenosis measured by quantitative coronary angiography.
      Patients referred for diagnostic cardiac catheterization with suspected but
      previously unknown CAD were enrolled. Noninvasive myocardial perfusion imaging
      (MPI) was available in 60% of patients. The GES, comprising gender-specific age
      functions and 6 gene expression terms containing 23 genes, was performed for all
      patients. RESULTS: A total of 1,160 consecutive patients (57.6% men and 42.4%
      women) were enrolled in PREDICT. The prevalence of obstructive CAD was 46.7% in
      men and 22.0% in women. Chest pain symptoms were a discriminator of obstructive
      CAD in men (P < .001) but not in women. The positive predictive value of MPI was
      significantly higher in men (45%) than in women (22%). An abnormal site-read MPI
      was not significantly associated with obstructive or severity of CAD. The GES was
      significantly associated with a 2-fold increase in the odds of obstructive CAD
      for every 10-point increment in the GES and had a significant association with
      all measures of severity and burden of CAD. By multivariable analysis, GES was an
      independent predictor of obstructive CAD in the overall population (odds ratio
      [OR] 2.53, P = .001) and in the male (OR 1.99, P = .001) and female (OR 3.45, P =
      .001) subgroups separately, whereas MPI was not. CONCLUSIONS: Commonly used
      diagnostic approaches including symptom evaluation and MPI performed less well in
      women than in men for identifying significant CAD. In contrast, gender-specific
      GES performed similarly in women and men. Gene expression score offers a reliable
      diagnostic approach for the assessment of nondiabetic patients and, in
      particular, women with suspected obstructive CAD.

PMID- 22980298
TI  - Comparison between initial and chronic response to clopidogrel therapy after
      coronary stenting for acute coronary syndrome and influence on clinical outcomes.
AB  - BACKGROUND: Studies have addressed the benefit of tailored therapy based on
      initial response to clopidogrel loading dose. However, the appropriate timing for
      platelet testing remains uncertain. METHODS: The present study was performed to
      compare initial clopidogrel response after 600 mg loading dose and 1-month
      platelet response and their relationship with ischemic and bleedings events. A
      total of 475 patients with non-ST-segment elevation acute coronary syndrome
      undergoing percutaneous coronary intervention have been included in the present
      study. All patients were treated with 600 mg clopidogrel followed by 150 mg
      daily. Clopidogrel low response was defined by high on-treatment platelet
      reactivity (HPR) with vasoactive stimulated phosphoprotein >50%, and
      "hyperresponse," as platelet reactivity index vasoactive stimulated
      phosphoprotein (PRI VASP) <95th percentile after 600 mg. RESULTS: After 600 mg,
      210 patients were identified with HPR (44%), and 23 patients (5%), with
      hyperresponse (PRI VASP <8%). At 1 month on 150 mg clopidogrel daily, 184
      patients (39%) had HPR (39%), 14 patients (3 %) had hyperresponse, and mean PRI
      VASP was significantly lower (43% +/- 19% vs 46% +/- 21%, P = .04). At 1 month,
      among the 210 patients with HPR after 600 mg, 127 (60%) remained, whereas among
      the 265 patients responders after 600 mg, only 57 (22%) remained with HPR (60% vs
      22%, P < .0001). Initial response was significantly associated with risk of stent
      thrombosis and bleeding complications, whereas 1-month assessment was only linked
      with bleeding events. CONCLUSION: In conclusion, the present study showed that
      initial clopidogrel response in patients with acute coronary syndrome is not a
      reliable predictor of response to maintenance therapy and their values for
      prediction of clinical outcome are likely to be different.

PMID- 22980299
TI  - Prior smoking status, clinical outcomes, and the comparison of ticagrelor with
      clopidogrel in acute coronary syndromes-insights from the PLATelet inhibition and
      patient Outcomes (PLATO) trial.
AB  - BACKGROUND: Habitual smoking has been associated with increased platelet
      reactivity, increased risk of thrombotic complications and greater efficacy of
      clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to
      clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary
      composite end point of vascular death, myocardial infarction and stroke, without
      increasing overall rates of major bleeding. We evaluated the results in relation
      to smoking habits. METHODS: Interactions between habitual smokers (n = 6678) and
      in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on
      ischemic and bleeding outcomes were evaluated by Cox regression analyses.
      RESULTS: Habitual smokers had an overall lower risk profile and more often ST
      elevation ACS. After adjustment for baseline imbalances, habitual smoking was
      associated with a higher incidence of definite stent thrombosis (adjusted HR,
      1.44 [95% CI, 1.07-1.94]); there were no significant associations with other
      ischemic or bleeding end points. The effects of ticagrelor compared to
      clopidogrel were consistent for all outcomes regardless of smoking status. Thus,
      there was a similar reduction in the primary composite end point for habitual
      smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR,
      0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis
      for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted
      HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61). CONCLUSIONS: In patients
      hospitalized with ACS, habitual smoking is associated with a greater risk of
      subsequent stent thrombosis. The reduction of vascular death, myocardial
      infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is
      consistent regardless of smoking habits.

PMID- 22980300
TI  - Efficacy of early invasive management post-fibrinolysis in men versus women with
      ST-elevation myocardial infarction: a subgroup analysis from Trial of Routine
      Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute
      Myocardial Infarction (TRANSFER-AMI).
AB  - BACKGROUND: The TRANSFER-AMI study demonstrated that early routine percutaneous
      coronary intervention post-fibrinolysis (pharmacoinvasive strategy) is superior
      to conservative management for ST-elevation myocardial infarction. However, it is
      not clear whether treatment efficacy differs between men and women. METHODS: In
      this pre-specified subgroup analysis, we compared the efficacy of a
      pharmacoinvasive strategy in men versus women with acute ST-elevation myocardial
      infarction who were randomized to a pharmacoinvasive versus standard management
      following fibrinolysis. The primary end point was a composite of death, recurrent
      myocardial infarction, recurrent ischemia, heart failure and shock at 30 days. We
      tested for treatment heterogeneity between men and women using the Breslow-Day
      test. We also performed multivariable analysis adjusting for GRACE risk score and
      its interaction with treatment assignment, and evaluated for death/recurrent
      myocardial reinfarction as a secondary outcome. RESULTS: Of the 1059 patients,
      843 were men and 216 were women. Compared to men, women were older, had worse
      Killip class, higher GRACE risk score, and higher rates of death and
      death/myocardial reinfarction at 30 days. The primary end point did not differ
      significantly between men and women (13.4% vs 16.7%, P = .22). Compared to
      standard treatment, a pharmacoinvasive strategy was associated with a lower rate
      of the primary end point in men (17.5% vs 9.4%, respectively, P < .001), but not
      in women (16.2% vs 17.1%, P = .86). There was a trend toward an interaction
      between treatment assignment and sex for the composite primary end point (P =
      .06). After adjustment for the significant interaction between GRACE risk score
      and treatment (P < .001), there was no significant interaction between sex and
      treatment for all the end points (all P > .40). CONCLUSION: The borderline
      heterogeneity in treatment efficacy of a pharmacoinvasive strategy in men versus
      women was no longer evident after adjustment for the difference in baseline risk.
      This suggests that sex per se was not an important determinant of the efficacy of
      a pharmacoinvasive strategy. Owing to the small number of women in this trial,
      further study in this area is needed.

PMID- 22980301
TI  - Troponin I release after intravenous treatment with high furosemide doses plus
      hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur).
AB  - BACKGROUND: High values of cardiac troponin in acute decompensated congestive
      heart failure (ADHF) identify patients at higher risk and worsened prognosis. A
      cardiac troponin increase during therapy indicates the need for more appropriate
      intervention, aimed at compensating cardiac disease and effectively minimizing
      myocardial wall stress and subsequent cytolysis. This study evaluated the effects
      of an intravenous high dose of furosemide with (group A) or without small volume
      hypertonic saline solution (HSS) (group B) on myocardial cytolysis in patients
      with ADHF. METHODS: A total of 248 consecutive patients with ADHF (148 men, mean
      age 74.9 +/- 10.9 years) were randomly assigned to group A or B. Plasma levels of
      cardiac troponin-I, brain natriuretic peptide, glomerular filtration rate by
      Modification of Diet in Renal Disease formula, bioelectrical impedance analysis
      measurements, and delta pressure/delta time (dP/dt) rate were observed on
      admission and discharge for all patients. RESULTS: We observed a significant
      reduction of cardiac troponin in both groups and a significant improvement in
      renal function, hydration state, pulmonary capillary wedge pressure (P < .0001),
      end diastolic volume (P < .01), ejection fraction (P < .01), and dP/dt (P < .004)
      in group A. We also observed a significant reduction in body weight (64.4 vs 75.8
      kg) (P < .001), cardiac troponin I (0.02 vs 0.31 ng/mL) (P < .0001) and brain
      natriuretic peptide (542 vs 1,284 pg/mL) (P < .0001), and hospitalization time
      (6.25 vs 10.2 days) (P < .0001) in the HSS group. CONCLUSIONS: These data
      demonstrate that intravenous high doses of furosemide do not increase myocardial
      injury and, in addition, when associated to HSS, significantly reduce cardiac
      troponin I release. This behavior is mirrored by the achievement of improved
      hemodynamic compensation at echocardiography and body hydration normalization.

PMID- 22980302
TI  - The natural history of new-onset heart failure with a severely depressed left
      ventricular ejection fraction: implications for timing of implantable
      cardioverter-defibrillator implantation.
AB  - BACKGROUND: Guidelines recommend that patients with new-onset systolic heart
      failure (HF) receive a trial of medical therapy before an implantable cardiac
      defibrillator (ICD). This strategy allows for improvement of left ventricular
      ejection fraction (LVEF), thereby avoiding an ICD, but exposes patients to risk
      of potentially preventable sudden cardiac death during the trial of medical
      therapy. METHODS: We reviewed a consecutive series of patients with HF of <6
      months duration with a severely depressed LVEF (<30%) evaluated in a HF clinic (N
      = 224). The ICD implantation was delayed with plans to reassess LVEF
      approximately 6 months after optimization of beta-blockers. Mortality was
      ascertained by the National Death Index. RESULTS: Follow-up echocardiograms were
      performed in 115 of the 224 subjects. Of these, 50 (43%) had mildly depressed or
      normal LVEF at follow-up ("LVEF recovery") such that an ICD was no longer
      indicated. In a conservative sensitivity analysis (using the entire study cohort,
      whether or not a follow-up echocardiogram was obtained, as the denominator), 22%
      of subjects had LVEF recovery. Mortality at 6, 12, and 18 months in the entire
      cohort was 2.3%, 4.5%, and 6.8%, respectively. Of 87 patients who tolerated
      target doses of beta-blockers, only 1 (1.1%) died during the first 18 months.
      CONCLUSION: Patients with new-onset systolic HF have both a good chance of LVEF
      recovery and low 6-month mortality. Achievement of target beta-blocker dose
      identifies a very low-risk population. These data support delaying ICD
      implantation for a trial of medical therapy.

PMID- 22980303
TI  - Predicting the risk of unplanned readmission or death within 30 days of discharge
      after a heart failure hospitalization.
AB  - BACKGROUND: The accuracy of current models to predict the risk of unplanned
      readmission or death after a heart failure (HF) hospitalization is uncertain.
      METHODS: We linked four administrative databases in Alberta to identify all
      adults discharged alive after a HF hospitalization between April 1999 and 2009.
      We randomly selected one episode of care per patient and evaluated the accuracy
      of five administrative data-based models (4 already published, 1 new) for
      predicting risk of death or unplanned readmission within 30 days of discharge.
      RESULTS: Over 10 years, 59652 adults (mean age 76, 50% women) were discharged
      after a HF hospitalization. Within 30 days of discharge, 11199 (19%) died or had
      an unplanned readmission. All 5 administrative data models exhibited moderate
      discrimination for this outcome (c-statistic between 0.57 and 0.61). Neither
      Centers for Medicare and Medicaid Services (CMS)-endorsed model exhibited
      substantial improvements over the Charlson score for prediction of 30-day post
      discharge death or unplanned readmission. However, a new model incorporating
      length of index hospital stay, age, Charlson score, and number of emergency room
      visits in the prior 6 months (the LaCE index) exhibited a 20.5% net
      reclassification improvement (95% CI, 18.4%-22.5%) over the Charlson score and a
      19.1% improvement (95% CI, 17.1%-21.2%) over the CMS readmission model.
      CONCLUSIONS: None of the administrative database models are sufficiently accurate
      to be used to identify which HF patients require extra resources at discharge.
      Models which incorporate length of stay such as the LaCE appear superior to
      current CMS-endorsed models for risk adjusting the outcome of "death or
      readmission within 30 days of discharge".

PMID- 22980304
TI  - Epidemiology, management, and outcomes of sustained ventricular arrhythmias after
      continuous-flow left ventricular assist device implantation.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are pivotal treatment options
      for patients with end-stage heart failure. Despite robust left ventricular
      unloading, the right ventricle remains unsupported and susceptible to hemodynamic
      perturbations from ventricular arrhythmias (VAs). Little is known about the
      epidemiology, management, resource use, and outcomes of sustained VAs in
      continuous-flow LVAD patients. METHODS: We reviewed data from all consecutive
      patients receiving a continuous-flow LVAD at the University of North Carolina
      from January 2006 to February 2011. Patient demographics, pharmacotherapies,
      resource use, and outcomes were recorded. Descriptive statistics were generated,
      and multivariable logistic regression was used to assess the independent
      association of clinical variables on the development of postimplantation VAs.
      RESULTS: Of 61 patients, 26 (43%) had sustained VAs after LVAD. Most were male
      (65%), had history of hypertension (65%), and had nonischemic cardiomyopathy
      (62%). Patients with VAs after LVAD more often had preimplant VAs (62% vs 14%, P
      < .01), prior implantable cardioverter-defibrillator (92% vs 71%, P = .04), and
      history of implantable cardioverter-defibrillator discharge (38% vs 11%, P <
      .01). Although length of stay was similar, those with postimplant VAs had greater
      rehospitalization rates, greater antiarrhythmic drug use, and frequently required
      external defibrillation. Using multivariable logistic regression, only history of
      prior VA was associated with postimplant arrhythmias (odds ratio 13.7, P < .001).
      CONCLUSIONS: Ventricular arrhythmias in LVAD patients are common, often
      refractory to conservative therapy, and associated with frequent
      rehospitalization. Post-LVAD VAs, however, did not significantly impact survival
      or transplantation rates. Arrhythmia burden should be considered before LVAD
      placement, and future study should focus on the impact of VAs on quality of life.

PMID- 22980305
TI  - Edifoligide and long-term outcomes after coronary artery bypass grafting: PRoject
      of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year
      results.
AB  - BACKGROUND: Edifoligide, an E2F transcription factor decoy, does not prevent vein
      graft failure or adverse clinical outcomes at 1 year in patients undergoing
      coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes
      of patients in PREVENT IV treated with edifoligide and placebo to identify
      predictors of long-term clinical outcomes. METHODS: A total of 3,014 patients
      undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier
      curves were generated to compare the long-term effects of edifoligide and
      placebo. A Cox proportional hazards model was constructed to identify factors
      associated with 5-year post-CABG outcomes. The main outcome measures were death,
      myocardial infarction (MI), repeat revascularization, and rehospitalization
      through 5 years. RESULTS: Five-year follow-up was complete in 2,865 patients
      (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar
      rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%),
      revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The
      composite outcome of death, MI, or revascularization occurred at similar
      frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%,
      respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated
      with death, MI, or revascularization at 5 years included peripheral and/or
      cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes
      mellitus, and congestive heart failure. CONCLUSIONS: Up to a quarter of patients
      undergoing CABG will have a major cardiac event or repeat revascularization
      procedure within 5 years of surgery. Edifoligide does not affect outcomes after
      CABG; however, common identifiable baseline and procedural risk factors are
      associated with long-term outcomes after CABG.

PMID- 22980306
TI  - Vitamin D levels do not predict cardiovascular events in statin-treated patients
      with stable coronary disease.
AB  - BACKGROUND: This post hoc nested case-control analysis of the TNT study was
      designed to investigate whether baseline vitamin D level is a significant
      predictor of cardiovascular risk among statin-treated patients and whether
      changes in vitamin D after treatment with atorvastatin are associated with
      improved cardiovascular outcomes. METHODS: A total of 10,001 patients with stable
      coronary heart disease were randomized to atorvastatin 80 or 10 mg for a median
      of 4.9 years. This analysis included 1,509 patients (497 with a subsequent
      cardiovascular event and 1,012 without an event) with vitamin D levels determined
      at baseline and 1 year. Event rates were analyzed by Cox proportional hazard
      model by baseline vitamin D levels, with vitamin D as a continuous variable, and
      with change in vitamin D level as the predictor. RESULTS: Vitamin D deficiency
      (<15 ng/mL) or insufficiency (15- <30 ng/mL) was present in 108 (7.2%) of 1,509
      and 625 (41.4%) of 1,509 of patients, whereas 46 (3.0%) of 1,509 had elevated
      vitamin D. There was no relationship between baseline vitamin D levels or change
      in vitamin D levels and cardiovascular events or mortality. Modeling of events
      with vitamin D as a continuous variable similarly showed no relationship of
      vitamin D to events. These findings held true after adjustment for seasonal
      variations in vitamin D and other confounders. CONCLUSION: In statin-treated
      patients with stable coronary heart disease, vitamin D levels did not predict
      cardiovascular risk. Changes in plasma concentrations of vitamin D after 1 year
      of treatment made no contribution to the efficacy of atorvastatin therapy.

PMID- 22980307
TI  - REstoration of COronary flow in patients with no-reflow after primary coronary
      interVEntion of acute myocaRdial infarction (RECOVER).
AB  - BACKGROUND: No randomized trial has been conducted to compare different
      vasodilators for treating no-reflow during primary percutaneous coronary
      intervention (PCI) for ST-segment elevation acute myocardial infarction. METHODS:
      The prospective, randomized, 2-center trial was designed to compare the effect of
      3 different vasodilators on coronary no-reflow. A total of 102 patients with no
      reflow in primary PCI were randomized to receive intracoronary infusion of
      diltiazem, verapamil, or nitroglycerin (n = 34 in each group) through selective
      microcatheter. The primary end point was coronary flow improvement in corrected
      thrombolysis in myocardial infarction frame count (CTFC) after administration of
      the drug. RESULTS: Compared with that of the nitroglycerin group, there was a
      significant improvement of CTFC after drug infusion in the diltiazem and
      verapamil groups (42.4 frames vs 28.1 and 28.4 frames, P < .001). The improvement
      in CTFC was similar between the diltiazem and verapamil groups (P = .9). Compared
      with the nitroglycerin group, the diltiazem and verapamil groups had more
      complete ST-segment resolution at 3 hours after PCI, lower peak troponin T level,
      and lower N-terminal pro-B-type natriuretic peptide levels at 1 and 30 days after
      PCI. After drug infusion, the drop of heart rate and systolic blood pressure in
      the verapamil group was greater than that in the diltiazem and nitroglycerin
      groups. CONCLUSION: Intracoronary infusion of diltiazem or verapamil can reverse
      no-reflow more effectively than nitroglycerin during primary PCI for acute
      myocardial infarction. The efficacy of diltiazem and verapamil is similar, and
      diltiazem seems safer.

PMID- 22980308
TI  - Adverse impact of bleeding and transfusion on the outcome post-transcatheter
      aortic valve implantation: insights from the Pooled-RotterdAm-Milano-Toulouse In
      Collaboration Plus (PRAGMATIC Plus) initiative.
AB  - BACKGROUND: Little is known about the impact of bleeding and red blood cells
      transfusion (RBC) on the outcome post transcatheter aortic valve implantation
      (TAVI). METHODS: Between November 2005 and August 2011, 943 consecutive patients
      underwent TAVI. Bleeding was assessed according to the Valve Academic Research
      Consortium definitions. Patients receiving RBC were compared to those not
      requiring transfusion. RESULTS: Life-threatening and major bleedings occurred
      respectively in 13.9% and 20.9% of the patients, significantly more frequently in
      the RBC cohort. Vascular complications occurred in 23.2% of the patients. Major
      and minor vascular complications were more frequent in the RBC group: 19.3 vs
      5.2%, P < .001; 15.3 vs 9%, P = .003, respectively. Thirty-day all-cause
      mortality was 7.2%. Of the overall cohort, 38.9% required RBC transfusion; those
      receiving at least 4 U of RBC had higher 30-day all-cause mortality than those
      receiving 1 to 4 U of RBC and those not requiring transfusion: 14.4%, vs 6.3% vs
      6.3%, respectively, P = .008. By multivariate analysis, transfusion of RBC was
      associated with an increased 30-day and 1-year mortality. Major stroke and all
      stages of acute kidney injury were significantly more frequent in the RBC cohort.
      CONCLUSIONS: Bleeding is frequent after TAVI, mainly driven by vascular
      complications. RBC transfusion was associated with increased mortality at 1 year
      and increased risk of major stroke and acute kidney injury. Specific scores are
      needed to identify the patients at higher risk for TAVI-related bleeding and RBC
      transfusion.

PMID- 22980309
TI  - Outcome of patients aged >=80 years undergoing combined aortic valve replacement
      and coronary artery bypass grafting: a systematic review and meta-analysis of 40
      studies.
AB  - AIM: This study was planned to evaluate the outcome of patients aged >=80 years
      undergoing combined conventional aortic valve replacement (AVR) and coronary
      artery bypass grafting (CABG). METHODS: This is a systematic review of the
      literature and meta-analysis of data on patients aged >=80 years who underwent
      combined AVR and CABG. RESULTS: The literature search yielded 40 observational
      studies reporting on 8,975 patients aged >=80 years. Pooled proportion of
      immediate postoperative mortality was 9.7% (95% CI 8.4-11.1, 40 studies, 8,975
      patients). Immediate mortality was 8.2% (95% CI 6.5-10.0) in 15 studies with a
      mid-date from 2000 to 2007 and 10.8% (95% CI 9.1-12.7) in 25 studies with a mid
      date from 1982 to 1999 (P = .043). Postoperative stroke rate was 3.7% (95% CI 2.8
      4.8, 12 studies, 2,770 patients), and postoperative implantation of pacemaker was
      4.3% (95% CI 2.6-6.5, 5 studies, 535 patients). The mean length of stay in
      intensive care unit was 5.3 days (95% CI 3.3-7.3, 5 studies, 490 patients), and
      the mean length of in-hospital stay was 16.9 days (95% CI 12.4-21.4, 5 studies,
      424 patients). One-, 3-, 5- and 10-year pooled survival rates after combined AVR
      and CABG were 83.2%, 72.9%, 60.8%, and 25.7%, respectively. CONCLUSIONS:
      Conventional AVR and CABG in patients aged >=80 years are associated with
      significant operative mortality and morbidity as well as prolonged in-hospital
      treatment. However, conventional surgery is associated with remarkably good late
      survival. This suggests that any alternative treatment modality must prove itself
      of being enough durable also in the very elderly.

PMID- 22980311
TI  - Disability, race/ethnicity, and medication adherence among Medicare myocardial
      infarction survivors.
AB  - BACKGROUND: Long-term medication therapy for patients with post-myocardial
      infarction (MI) can prolong life. However, recent data on long-term adherence are
      limited, particularly among some subpopulations. We compared medication adherence
      among Medicare MI survivors by disability status, race/ethnicity, and income.
      METHODS: We examined 100% of Medicare fee-for-service beneficiaries discharged
      post-MI in 2008. The outcomes were adherence to beta-blockers, statins, and
      angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, for 1
      year and 6-month postdischarge. Adherence was defined as having prescriptions in
      possession for >=75% of days. RESULTS: Among aged beneficiaries who survived 1
      year adherence to beta-blockers were 68%, 66%, 61%, 58%, and 57% for whites,
      Asians, Hispanics, Native Americans, and blacks, respectively; among persons with
      disability, 1-year adherence was worse for each group: 59%, 54%, 52%, 47%, and
      43%, respectively. The racial/ethnic difference persisted after adjustment for
      age, gender, income, drug coverage, location, and health status. Patterns of
      adherence to statins and angiotensin-converting enzymes/angiotensin II receptor
      blockers were similar. Among beneficiaries with close-to-full drug coverage,
      minorities were still less likely to adhere relative to whites: odds ratio 0.70
      (95% CI 0.65-0.75) for blacks and odds ratio 0.70 (95% CI 0.55-0.90) for Native
      Americans. CONCLUSIONS: Although beta-blockers at discharge has improved since
      the National Committee for Quality Assurance implemented quality measures, long
      term adherence remains problematic, especially among persons with disability and
      minority beneficiaries. Quality measures for long-term adherence should be
      created to improve outcomes in patients with post-MI. Even among those with close
      to-full drug coverage, racial differences remain, suggesting that policies simply
      relying on cost reduction cannot eliminate racial differences.

PMID- 22980312
TI  - Race and gender variation in the QT interval and its association with mortality
      in patients with coronary artery disease: results from the Duke Databank for
      Cardiovascular Disease (DDCD).
AB  - BACKGROUND: In several studies, prolongation of the corrected QT (QTc) interval
      has been associated with an increased risk of cardiac events. However, data on
      race and gender variation in the QTc and its associated risk of death are
      lacking. METHODS: We prospectively followed 19,252 subjects who underwent cardiac
      catheterization and had at least 1 native coronary artery stenosis >=75%.
      Automated QTc measurements were obtained from a baseline electrocardiogram.
      RESULTS: The mean age of the population was 62.4 years, with 35% being female and
      20% being black. The QTc varied by gender and race (417.9 +/- 34.4 ms in men and
      433.4 +/- 33.6 ms in women, 422.1 +/- 34.3 ms in whites and 428.1 +/- 36.9 ms in
      blacks; P < .0001 for both). Risk factors most strongly associated with a
      prolonged QTc were lower ejection fraction, higher diastolic blood pressure,
      history of myocardial infarction, and lower glomerular filtration rate. Black
      race and female gender were also independently associated with a prolonged QTc,
      after adjustment for cardiac risk factors. Moreover, there was an independent
      association between QTc and all-cause mortality (hazard ratio 1.037 per 10-ms
      increase, P < .0001). The increased mortality risk associated with a 10-ms
      increase in the QTc interval was significantly greater for men compared with
      women (4.6% vs 2.4%, P = .004) and slightly greater for blacks compared with
      other races (5.0% vs 3.3%, P = .057). CONCLUSIONS: Among patients with coronary
      artery disease, QTc prolongation is independently associated with all-cause
      mortality. The increased mortality risk is higher for men than for women, with a
      trend toward higher mortality in blacks.

PMID- 22980310
TI  - N-terminal pro-brain natriuretic peptide levels and aortic diameters.
AB  - BACKGROUND: Women with X-chromosome monosomy or Turner syndrome (TS) are at
      increased risk for aortic dilation and dissection. To better understand the
      pathology and develop tools to monitor the risk of aortic disease, we
      investigated N-terminal pro-brain natriuretic peptide (BNP) (NT-proBNP) levels in
      women with TS and healthy female controls. METHODS: We evaluated NT-proBNP levels
      in women with karyotype-proven TS and healthy female volunteers in relation to
      ascending aortic diameter and descending aortic diameter measured by
      cardiovascular magnetic resonance imaging. RESULTS: The NT-proBNP levels were
      strongly and positively correlated with ascending aortic diameter and descending
      aortic diameter in both cohorts. The TS group (n = 114, age 37.4 +/- 12 yr) had
      greater body surface area-indexed aortic diameters and higher NT-proBNP levels
      than the control group (n = 27, age 46.4 +/- 11 years): 88.3 +/- 62.7 versus 53.5
      +/- 35 pg/mL, P = .0003. Within the TS group, NT-proBNP levels were higher in
      those with dilated ascending aorta (n = 42, 112.4 +/- 75.7 pg/mL) compared with
      those with normal aortic dimensions (n = 72, 74.2 +/- 49 pg/mL, P = .0014).
      Abnormally high NT-pro BNP levels were seen in 3 of 4 TS women who presented with
      previously undetected aortic aneurysm and/or dissection. CONCLUSIONS: The NT
      proBNP levels are positively associated with aortic diameters in women with and
      without TS, suggesting a role for BNP in arterial wall homeostasis. Further study
      is necessary to determine whether NT-proBNP measurement may be used to monitor
      aortic diameter and/or detect aortic pathology in individuals at risk for aortic
      disease.

PMID- 22980313
TI  - Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a
      study from the Pediatric Cardiomyopathy Registry.
AB  - BACKGROUND: Studies of cardiomyopathy in children with Noonan syndrome (NS) have
      been primarily small case series or cross-sectional studies with small or no
      comparison groups. METHODS: We used the Pediatric Cardiomyopathy Registry
      database to compare the survival experience of children with NS and hypertrophic
      cardiomyopathy (HCM) with children with idiopathic or familial HCM and to
      identify clinical and echocardiographic predictors of clinical outcomes. RESULTS:
      Longitudinal data in 74 children with NS and HCM and 792 children with idiopathic
      or familial isolated HCM were compared. Children with NS were diagnosed with HCM
      before 6 months old more often (51%) than children with HCM (28%) and were more
      likely to present with congestive heart failure (CHF) (24% vs 9%). The NS cohort
      had lower crude survival than the group with other HCM (P = .03), but survival
      did not differ after adjustment for CHF and age at diagnosis. Within the NS
      cohort (1-year survival 78%), a diagnosis of HCM before age 6 months with CHF
      resulted in 31% 1-year survival. Lower height-for-age z score (hazard ratio 0.26,
      P = .005) in place of CHF and lower left ventricular fractional shortening z
      score (hazard ratio 0.79, P = .04) also independently predicted mortality.
      CONCLUSIONS: Patients with NS with HCM have a worse risk profile at presentation
      compared with other children with HCM, resulting in significant early mortality
      (22% at 1 year). Decreased height-for-age and lower, although still supranormal,
      left ventricular fractional shortening z score are independent predictors of
      mortality in patients with NS with HCM. Such patients should have an aggressive
      therapeutic approach including potential listing for cardiac transplantation.

PMID- 22980314
TI  - Erythropoietin studies should not be abandoned.

PMID- 22980315
TI  - Evaluation of the effects of bitopertin (RG1678) on cardiac repolarization: a
      thorough corrected QT study in healthy male volunteers.
AB  - BACKGROUND: Bitopertin (RG1678) is a selective glycine reuptake inhibitor
      currently in Phase III development for the treatment of schizophrenia. Thorough
      QT studies to assess the effects of candidate drugs on cardiac repolarization and
      proarrhythmic potential are required by regulatory authorities and are a common
      part of the drug development process. A clinically relevant effect on QT interval
      is suspected if prolongation of the corrected QT interval (QTc) is ~5
      milliseconds or more, evidenced by an upper 1-sided 95% CI for the mean effect on
      the QTc of at least 10 milliseconds. OBJECTIVE: The goal of this study was to
      investigate the effect of bitopertin on the QTc interval in healthy male
      volunteers. METHODS: This was a multiple-dose, randomized, double-blind, double
      dummy, placebo-controlled, parallel-group study using bitopertin 30 mg (n = 56)
      or bitopertin 175 mg (n = 56) once daily for 10 days plus placebo on day 11,
      moxifloxacin 400 mg on day 1 plus placebo once daily for 10 days (n = 29), or
      placebo once daily for 10 days plus moxifloxacin 400 mg on day 11 (n = 28).
      Continuous Holter ECGs were obtained on days -1, 1, 10, and 11, and the placebo
      corrected mean change from time-matched baseline in the QT interval calculated by
      using Fridericia's formula (QTcF) on day 10 was the primary end point.
      Pharmacokinetic parameters of bitopertin were determined on day 10 by using HPLC
      MS/MS methods to obtain bitopertin plasma drug concentrations. Adverse events
      were recorded throughout the study. RESULTS: A total of 169 predominantly white,
      healthy male volunteers (mean age, 31.8 years; range, 19-59 years) were
      randomized to treatment; 162 completed the study. The mean change in placebo
      corrected QTcF from baseline to day 10 of bitopertin ranged from -2.8 to 3.9
      milliseconds. The upper bound of the 1-sided 95% CI was <10 milliseconds at all
      time points with both doses. There was no relation between bitopertin
      concentrations and changes in QTcF or other ECG variables. Assay sensitivity was
      confirmed by a placebo-corrected mean change from time-matched baseline in QTcF
      of 10.6 milliseconds (lower bound of the 1-sided 98.3% CI, 6.9 milliseconds) 4
      hours after moxifloxacin administration. Peak bitopertin plasma concentrations
      were achieved ~4 hours after dosing. The terminal elimination t(1/2) was ~53
      hours. No safety or tolerability concerns were noted with bitopertin at either
      dose. Dizziness, nausea, and blurred vision were more common in the bitopertin
      175-mg group compared with the bitopertin 30-mg or placebo groups. CONCLUSION:
      Multiple dosing with bitopertin 30 mg or 175 mg did not affect QTcF in these
      healthy male volunteers. ClinicalTrials.gov identifier: NCT01613040.

PMID- 22980316
TI  - Reversibly light-modulated dirac point of graphene functionalized with
      spiropyran.
AB  - Graphene has been functionalized with spiropyran (SP), a well-known photochromic
      molecule. It has been realized with pyrene-modified SP, which has been adsorbed
      on graphene by pi-pi interaction between pyrene and graphene. The field-effect
      transistor (FET) with SP-functionalized graphene exhibited n-doping effect and
      interesting optoelectronic behaviors. The Dirac point of graphene in the FET
      could be controlled by light modulation because spiropyran can be reversibly
      switched between two different conformations, a neutral form (colorless SP) and a
      charge-separated form (purple colored merocyanine, MC), on UV and visible light
      irradiation. The MC form is produced during UV light irradiation, inducing the
      shift of the Dirac point of graphene toward negative gate voltage. The reverse
      process back to the neutral SP form occurred under visible light irradiation or
      in darkness, inducing a shift of the Dirac point toward positive gate voltage.
      The change of the Dirac point by UV and visible light was reproducibly repeated.
      SP molecules also improved the conductance change in the FET device. Furthermore,
      dynamics on conversion from MC to SP on graphene was different from that in
      solution and solid samples with SP-grafted polymer or that on gold nanoparticles.

PMID- 22980317
TI  - Qualitative screening in doping control by MALDI-TOF/TOF mass spectrometry: a
      proof-of-evidence.
AB  - The analysis of doping agents in biological fluids is of top significance in
      clinical and forensic toxicology. Herein we describe the study of a screening
      method for the detection of a mixture of drugs of potential abuse including
      cocaine and its metabolites. By using matrix-assisted laser desorption/ionization
      MALDI-TOF/TOF mass spectrometry. This screening procedure to detect the presence
      of different drugs, avoiding time consuming procedures could be useful in
      different fields of forensic analytical toxicology, including antidoping
      analysis.

PMID- 22980318
TI  - Protein quantitation using various modes of high performance liquid
      chromatography.
AB  - Pharmaceuticals based on proteins (biologicals), such as monoclonal antibodies
      (mAb), attain more and more relevance since they were established as potent drugs
      in anticancer therapy or for the treatment of autoimmune based diseases. Due to
      their high efficiency it is essential to have accurate and precise methods for
      protein quantitation and the detection of protein aggregates, which in some cases
      may lead to adverse effects after application. Selectivity and precision of
      traditional protein quantification methods such as the Bradford assay or SDS-PAGE
      are insufficient for quality control (QC) purposes. In this work several HPLC
      separation modes, which can significantly improve these important parameters,
      were compared for their application in this field. High performance size
      exclusion (HP-SEC), strong anion exchange (SAX), weak cation exchange (WCX) as
      well as reversed phase chromatography are all already successfully applied in
      protein analysis. Good precision (SEC: <1.9%, SAX: <5%, RP: <2% and WCX: <3.5% -
      RSD% for peak areas day-to-day), high selectivity and low quantitation limits
      (<15MUg/ml) for the model proteins ovalbumin, myoglobin and bovine serum albumin
      (BSA), respectively cytochrome c and lysozyme in the cation exchange mode, could
      be achieved. Consecutively, the four separation modes were compared to each other
      and to electrophoretic techniques in terms of precision, selectivity, analysis
      time, effort of sample and mobile phase preparation as well as separating
      capacity. Moreover, the analysis of an IgG1-type antibody was included in this
      study.

PMID- 22980319
TI  - Determination of bulleyaconitine A in plasma by a sensitive LC-MS/MS method and
      its application to an oral pharmacokinetic study in rats.
AB  - A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was
      developed and validated for the quantification of bulleyaconitine A (BLA)
      concentration in rat plasma. An aliquot of 100MUL plasma sample was prepared by
      liquid-liquid extraction with diethyl ether. Chromatographic separation was
      accomplished on a Phenomenex Luna C(18) column (50mm*2.00mm, 5MUm) utilizing a
      isocratic mobile phase consisting of (A) 0.1% formic acid in methanol and (B)
      formic acid in water. Detection was performed by multiple reaction monitoring
      (MRM) mode using electrospray ionization in the positive ion mode. The optimized
      fragmentation transitions for MRM were m/z 644.4->m/z 584.3 for BLA and m/z 632.4
      >m/z 572.3 for mesaconitine (IS). The method was linear over the concentration
      range of 0.02-20.0ng/mL. The intra and inter-day variance are less than 6.1% and
      accuracy is within +/-9.0%. The validated method was successfully applied to
      pharmacokinetic study in rat after single oral administration of 40MUg/kg of BLA
      and the oral pharmacokinetic data of BLA have been demonstrated for the first
      time.

PMID- 22980320
TI  - Role of cellular senescence in hepatic wound healing and carcinogenesis.
AB  - A state of permanent growth arrest characterises a senescent cell. Both the
      beneficial and deleterious effects that have accrued in senescent cells are
      observed in a complex organ, such as the liver. Injury to liver tissues triggers
      processes of regeneration and associated wound healing. Persistent injury can
      also lead to the neoplastic state. Recent evidence linked the senescent
      characteristics of the cells to the beneficial processes of wound healing and
      tumour surveillance in the liver. On the other hand, the secretory phenotype of
      senescent cells can also selectively promote undesirable neoplastic progression.
      In an evolutionary context, a senescent cell can function primarily as an
      adaptive response featuring the characteristics of altruism, trade-offs and
      bystander effects. Using the liver cell as a model system, this review focuses on
      the current knowledge of the role of senescence in these seemingly contradictory
      cell phenomena.

PMID- 22980321
TI  - Gut microbes make for fattier fish.
AB  - The mammalian gut microbiota influences both sides of the energy balance
      equation, salvaging energy from undigested nutrients and directing the host to
      accumulate adipose tissue. Semova et al. (2012) use zebrafish to demonstrate that
      the gut microbiota also promotes dietary lipid absorption, emphasizing the many
      host-microbial interactions contributing to adiposity.

PMID- 22980322
TI  - "With a little help from my friends": efferocytosis as an antimicrobial
      mechanism.
AB  - The uptake of apoptotic cells by phagocytes is defined as efferocytosis. In this
      issue of Cell Host & Microbe, Martin et al. (2012) and Yang et al. (2012) report
      that macrophage- and neutrophil-mediated efferocytosis of apoptotic cells
      containing mycobacteria is an innate antibacterial effector mechanism.

PMID- 22980323
TI  - Vaccinia virus egress: actin OUT with clathrin.
AB  - To ensure spread from one cell to another, exocytosed vaccinia virions recruit
      cellular actin polymerization machinery to blast off from the cell surface on
      actin tails. Humphries et al. (2012) now show that the virus exploits clathrin to
      organize viral factors into a launch pad that facilitates efficient actin tail
      formation.

PMID- 22980324
TI  - Pathogenic pore-forming proteins: function and host response.
AB  - Organisms from all kingdoms produce pore-forming proteins, with the best
      characterized being of bacterial origin. The last decade of research has revealed
      that the channels formed by these proteins can be very diverse, thus
      differentially affecting target cell-membrane permeability and consequent
      cellular outcome. The responses to these toxins are also extremely diverse due to
      multiple downstream effects of pore-induced changes in ion balance. Determining
      the secondary effects of pore-forming toxins is essential to understand their
      contribution to infection.

PMID- 22980325
TI  - Microbiota regulate intestinal absorption and metabolism of fatty acids in the
      zebrafish.
AB  - Regulation of intestinal dietary fat absorption is critical to maintaining energy
      balance. While intestinal microbiota clearly impact the host's energy balance,
      their role in intestinal absorption and extraintestinal metabolism of dietary fat
      is less clear. Using in vivo imaging of fluorescent fatty acid (FA) analogs
      delivered to gnotobiotic zebrafish hosts, we reveal that microbiota stimulate FA
      uptake and lipid droplet (LD) formation in the intestinal epithelium and liver.
      Microbiota increase epithelial LD number in a diet-dependent manner. The presence
      of food led to the intestinal enrichment of bacteria from the phylum Firmicutes.
      Diet-enriched Firmicutes and their products were sufficient to increase
      epithelial LD number, whereas LD size was increased by other bacterial types.
      Thus, different members of the intestinal microbiota promote FA absorption via
      distinct mechanisms. Diet-induced alterations in microbiota composition might
      influence fat absorption, providing mechanistic insight into how microbiota-diet
      interactions regulate host energy balance.

PMID- 22980326
TI  - Efferocytosis is an innate antibacterial mechanism.
AB  - Mycobacterium tuberculosis persists within macrophages in an arrested phagosome
      and depends upon necrosis to elude immunity and disseminate. Although apoptosis
      of M. tuberculosis-infected macrophages is associated with reduced bacterial
      growth, the bacteria are relatively resistant to other forms of death, leaving
      the mechanism underlying this observation unresolved. We find that after
      apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by
      uninfected macrophages through efferocytosis, a dedicated apoptotic cell
      engulfment process. Efferocytosis of M. tuberculosis sequestered within an
      apoptotic macrophage further compartmentalizes the bacterium and delivers it
      along with the apoptotic cell debris to the lysosomal compartment. M.
      tuberculosis is killed only after efferocytosis, indicating that apoptosis itself
      is not intrinsically bactericidal but requires subsequent phagocytic uptake and
      lysosomal fusion of the apoptotic body harboring the bacterium. While
      efferocytosis is recognized as a constitutive housekeeping function of
      macrophages, these data indicate that it can also function as an antimicrobial
      effector mechanism.

PMID- 22980327
TI  - Neutrophils exert protection in the early tuberculous granuloma by oxidative
      killing of mycobacteria phagocytosed from infected macrophages.
AB  - Neutrophils are typically the first responders in host defense against invading
      pathogens, which they destroy by both oxidative and nonoxidative mechanisms.
      However, despite a longstanding recognition of neutrophil presence at disease
      sites in tuberculosis, their role in defense against mycobacteria is unclear.
      Here we exploit the genetic tractability and optical transparency of zebrafish to
      monitor neutrophil behavior and its consequences during infection with
      Mycobacterium marinum, a natural fish pathogen. In contrast to macrophages,
      neutrophils do not interact with mycobacteria at initial infection sites.
      Neutrophils are subsequently recruited to the nascent granuloma in response to
      signals from dying infected macrophages within the granuloma, which they
      phagocytose. Some neutrophils then rapidly kill the internalized mycobacteria
      through NADPH oxidase-dependent mechanisms. Our results provide a mechanistic
      link to the observed patterns of neutrophils in human tuberculous granulomas and
      the susceptibility of humans with chronic granulomatous disease to mycobacterial
      infection.

PMID- 22980328
TI  - Sustained generation of nitric oxide and control of mycobacterial infection
      requires argininosuccinate synthase 1.
AB  - Nitric oxide (NO) defends against intracellular pathogens, but its synthesis must
      be regulated due to cell and tissue toxicity. During infection, macrophages
      import extracellular arginine to synthesize NO, generating the byproduct
      citrulline. Accumulated intracellular citrulline is thought to fuel arginine
      synthesis catalyzed by argininosuccinate synthase (Ass1) and argininosuccinate
      lyase (Asl), which would lead to abundant NO production. Instead, we find that
      citrulline is exported from macrophages during early stages of NO production with
      <2% retained for recycling via the Ass1-Asl pathway. Later, extracellular
      arginine is depleted, and Ass1 expression allows macrophages to synthesize
      arginine from imported citrulline to sustain NO output. Ass1-deficient
      macrophages fail to salvage citrulline in arginine-scarce conditions, leading to
      their inability to control mycobacteria infection. Thus, extracellular arginine
      fuels rapid NO production in activated macrophages, and citrulline recycling via
      Ass1 and Asl is a fail-safe system that sustains optimum NO production.

PMID- 22980329
TI  - Intravascular neutrophil extracellular traps capture bacteria from the
      bloodstream during sepsis.
AB  - During the systemic inflammatory response of severe sepsis, neutrophils
      accumulate in the liver microcirculation, but their functional significance is
      largely unknown. We show that neutrophils migrate to liver sinusoids during
      endotoxemia and sepsis where they exert protective effects by releasing
      neutrophil extracellular traps (NETs), which are DNA-based structures that
      capture and eliminate microbes. NETs released into the vasculature ensnare
      bacteria from the bloodstream and prevent dissemination. NET production requires
      platelet-neutrophil interactions and can be inhibited by platelet depletion or
      disruption of integrin-mediated platelet-neutrophil binding. During sepsis, NET
      release increases bacterial trapping by 4-fold (beyond the basal level provided
      by resident intravascular macrophages). Blocking NET formation reduces the
      capture of circulating bacteria during sepsis, resulting in increased
      dissemination to distant organs. Thus, NETs ensnare circulating bacteria and
      provide intravascular immunity that protects against bacterial dissemination
      during septic infections.

PMID- 22980331
TI  - Clathrin potentiates vaccinia-induced actin polymerization to facilitate viral
      spread.
AB  - During their egress, newly assembled vaccinia virus particles fuse with the
      plasma membrane and enhance their spread by inducing Arp2/3-dependent actin
      polymerization. Investigating the events surrounding vaccinia virus fusion, we
      discovered that vaccinia transiently recruits clathrin in a manner dependent on
      the clathrin adaptor AP-2. The recruitment of clathrin to vaccinia dramatically
      enhances the ability of the virus to induce actin-based motility. We demonstrate
      that clathrin promotes clustering of the virus actin tail nucleator A36 and host
      N-WASP, which activates actin nucleation through the Arp2/3 complex. Increased
      clustering enhances N-WASP stability, leading to more efficient actin tail
      initiation and sustained actin polymerization. Our observations uncover an
      unexpected role for clathrin during virus spread and have important implications
      for the regulation of actin polymerization.

PMID- 22980330
TI  - A neuron-specific role for autophagy in antiviral defense against herpes simplex
      virus.
AB  - Type I interferons (IFNs) are considered to be the universal mechanism by which
      viral infections are controlled. However, many IFN-stimulated genes (ISGs) rely
      on antiviral pathways that are toxic to host cells, which may be detrimental in
      nonrenewable cell types, such as neurons. We show that dorsal root ganglionic
      (DRG) neurons produced little type I IFNs in response to infection with a
      neurotropic virus, herpes simplex type 1 (HSV-1). Further, type I IFN treatment
      failed to completely block HSV-1 replication or to induce IFN-primed cell death
      in neurons. We found that DRG neurons required autophagy to limit HSV-1
      replication both in vivo and in vitro. In contrast, mucosal epithelial cells and
      other mitotic cells responded robustly to type I IFNs and did not require
      autophagy to control viral replication. These findings reveal a fundamental
      difference in the innate antiviral strategies employed by neurons and mitotic
      cells to control HSV-1 infection.

PMID- 22980332
TI  - Tetherin/BST-2 is essential for the formation of the intracellular virus
      containing compartment in HIV-infected macrophages.
AB  - HIV-1 assembly and release occur at the plasma membrane in T lymphocytes, while
      intracellular sites of virus assembly or accumulation are apparent in
      macrophages. The host protein tetherin (BST-2) inhibits HIV release from the
      plasma membrane by retaining viral particles at the cell surface, but the role of
      tetherin at intracellular HIV assembly sites is unclear. We determined that
      tetherin is significantly upregulated upon macrophage infection and localizes to
      an intracellular virus-containing compartment (VCC). Tetherin localized at the
      virus-VCC membrane interface, suggesting that tetherin physically tethers virions
      in VCCs. Tetherin knockdown diminished and redistributed VCCs within macrophages
      and promoted HIV release and cell-cell transmission. The HIV Vpu protein, which
      downregulates tetherin from the plasma membrane, did not fully overcome tetherin
      mediated restriction of particle release in macrophages. Thus, tetherin is
      essential for VCC formation and may account for morphologic differences in the
      apparent HIV assembly sites in macrophages versus T cells.

PMID- 22980334
TI  - Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex
      and recycling network to inhibit host cell secretion.
AB  - Shigella infection causes destruction of the human colonic epithelial barrier.
      The Golgi network and recycling endosomes are essential for maintaining
      epithelial barrier function. Here we show that Shigella epithelial invasion
      induces fragmentation of the Golgi complex with consequent inhibition of both
      secretion and retrograde transport in the infected host cell. Shigella induces
      tubulation of the Rab11-positive compartment, thereby affecting cell surface
      receptor recycling. The molecular process underlying the observed damage to the
      Golgi complex and receptor recycling is a massive redistribution of plasma
      membrane cholesterol to the sites of Shigella entry. IpaB, a virulence factor of
      Shigella that is known to bind cholesterol, is necessary and sufficient to induce
      Golgi fragmentation and reorganization of the recycling compartment. Shigella
      infection-induced Golgi disorganization was also observed in vivo, suggesting
      that this mechanism affecting the sorting of cell surface molecules likely
      contributes to host epithelial barrier disruption associated with Shigella
      pathogenesis.

PMID- 22980333
TI  - Reacquisition of Nef-mediated tetherin antagonism in a single in vivo passage of
      HIV-1 through its original chimpanzee host.
AB  - The interferon-induced host restriction factor tetherin poses a barrier for SIV
      transmission from primates to humans. After cross-species transmission, the
      chimpanzee precursor of pandemic HIV-1 switched from the accessory protein Nef to
      Vpu to effectively counteract human tetherin. As we report here, the experimental
      reintroduction of HIV-1 into its original chimpanzee host resulted in a virus
      that can use both Vpu and Nef to antagonize chimpanzee tetherin. Functional
      analyses demonstrated that alterations in and near the highly conserved ExxxLL
      motif in the C-terminal loop of Nef were critical for the reacquisition of
      antitetherin activity. Strikingly, just two amino acid changes allowed HIV-1 Nef
      to counteract chimpanzee tetherin and promote virus release. Our data demonstrate
      that primate lentiviruses can reacquire lost accessory gene functions during a
      single in vivo passage and suggest that other functional constraints keep Nef
      ready to regain antitetherin activity.

PMID- 22980335
TI  - Investigation of the central line of 11B in hexagonal boron nitride by a one
      dimensional single pulse nutation NMR experiment.
AB  - Spin-3/2 central line intensities are calculated for any ratio of the quadrupolar
      coupling constant to the radiofrequency field for the one-pulse NMR experiment.
      The sequence is then used to obtain the quadrupolar coupling constant on a powder
      sample of hexagonal boron nitride. This technique is found to be particularly
      useful when the NMR spectrum is featureless.

PMID- 22980336
TI  - Predictors of self-rated health and lifestyle behaviours in Swedish university
      students.
AB  - BACKGROUND: Lifestyle behaviours are usually formed during youth or young
      adulthood which makes college students a particularly vulnerable group that
      easily can adopt unhealthy lifestyle behaviour. AIM: The aim of this cross
      sectional study was to explore the influence of socio-demographic factors on
      Swedish university students' lifestyle behaviours and self-rated health. METHOD:
      Data were collected from a convenience sample of 152 students using
      questionnaires consisting of a socio-demographic section followed by previously
      well-validated instruments. Data were analysed using descriptive statistics: t
      tests, analysis of variance (ANOVA) and regression tests. FINDINGS: The results
      of this study show that the lifestyle behaviours under study (physical activity,
      perceived stress and eating behaviours) as well as self-rated health can be
      predicted to a certain extent by socio-demographic factors such as gender, mother
      tongue and parents' educational level. Male university students were shown to be
      physically more active than female students; the male students were less stressed
      and rated their overall health, fitness level and mental health higher. Female
      students were more prone to adopt unhealthy eating behaviours. DISCUSSION: This
      study addresses gender differences and their influences on lifestyle behaviours;
      it provides both theoretical explanations for these differences as well as
      presents some practical implications of the findings.

PMID- 22980338
TI  - Knowledge, attitudes and practice of condom use among males aged (15-49) years in
      Erbil Governorate.
AB  - BACKGROUND AND OBJECTIVES: Globally, condom is an important method of family
      planning and prevention of sexually transmitted infections especially human
      immune deficiency virus HIV/ acquired immune deficiency syndrome AIDS. Family
      planning saves lives of women and children and improves the quality of life. This
      study was conducted to assess knowledge, attitudes and practices in addition to
      socio-demographic factors of condom use among males in Erbil governorate.
      SUBJECTS AND METHOD: A cross sectional study conducted on randomly selected
      sample of 600 males aged 15-49 years from 3 districts of Erbil governorate of
      Iraqi Kurdistan region by using multistage cluster sampling method to assess
      their knowledge, attitudes and practice of condom use. RESULTS: Only 12% of
      respondents had ever used condoms. The main reason for condom use was for family
      planning in about 91.7%. About a quarter of respondents reported knowing how to
      use condom correctly. Condoms were considered by respondents as an effective
      method of contraception and prevention of sexually transmitted infections 33.2%
      and 28.3% respectively. While 30.3% of them believed that condom use had some
      harmful effects. The main reason to non condom use was lack of need in 45.5%,
      fertility related reasons in 17% and the use of other methods by the female
      partner 13.6%. Although 64% of respondents heard about AIDS /HIV and 71.7% about
      STIS in general, only few felt that they are at risk of STIs 9.5% and HIV
      infection 8.5%. CONCLUSION: The study showed that the rate of condom use was low
      among the studied sample. This was due to lack of knowledge about proper and
      effective use of condoms, low perception of risk of HIV and other STIs,
      misperception about harmful effects of condoms and the use of other family
      planning methods by respondents and their female sexual partner.

PMID- 22980337
TI  - An attributional analysis of stigma associated with sexually transmitted diseases
      and its relationship  with communication efficacy.
AB  - People typically attribute more responsibility to those individuals who are
      infected with sexually transmitted diseases (STD) than other diseases. This study
      tested how different routes (i.e., sexually transmitted or foodborne) of
      transmission have an impact on individuals' general perception on stigma/shame
      and the attributions of responsibility, when controlling for symptoms/conditions
      of the hypothetical virus infection. Two hundreds and ninety eight college
      students were recruited for the study. As predicted, people who were attributed
      with control over contracting the virus (i.e., sexually transmitted route) were
      likely to be assigned a greater level of personal responsibility and were more
      likely to receive blame from others than people who were attributed relatively
      less control over contracting the virus (i.e., foodborne). The relationship
      between the attribution of responsibility and communication efficacy was also
      assessed. The results supported our prediction that there was a significant
      association between the attribution of responsibility and communication efficacy,
      in that the perceived controllability of the situation, perceived responsibility
      for the situation, and blame were all significantly correlated with communication
      efficacy in a negative direction. Practical applications by evaluating the
      effectiveness of the actual Merck's Gardasil advertisement were discussed that
      the Gardasil advertisement appears to reduce the perceived shame and stigma
      associated with the sexually transmitted nature of the virus by not revealing the
      true nature of the virus upfront.

PMID- 22980339
TI  - Socio-demographic characteristics of health care workers and hepatitis B virus
      (HBV) infection in public teaching hospitals in Khartoum State, Sudan.
AB  - BACKGROUND: HBV is second to tobacco as a known human carcinogen and the 10th
      leading cause of death worldwide. OBJECTIVES: To examine the socio-demographic
      characteristics of health care workers and hepatitis B virus in Public Teaching
      Hospitals in Khartoum State, Sudan, in 2004. METHODS: It was an observational,
      cross sectional, facility-based study. A total of 843 subjects were selected. It
      was conducted through multistage cluster sampling. The clustering was based on:
      type of hospital (Federal or State) and degree of exposure (type of department).
      For the analysis, Z-test for single proportion and some non-parametric tests such
      as Chi-Square test were used. RESULTS: Among the 843 subjects tested for HBV
      markers (Anti-HBc, HBsAg, HBsAb, and HBeAg), the prevalence of Anti-HBc, HBsAg,
      HBsAb, and HBeAg was found to be 57%, 6%, 37% and 9% respectively. Seroprevalence
      of all HBV markers was found to be statistically significant with demographic
      factors (P<0.05). CONCLUSION: Infection rate, carrier rate and a profile of high
      infectivity rate were found to be high. The immunity rate was low. There is a
      significant association between HBV markers and socio-demographic
      characteristics. Highest rate of infection was found in State Hospitals, South
      and West regions, married HCWs and HCWs of age group 30-49.

PMID- 22980340
TI  - Factors associated with an absence of effect of an education program for
      improving knowledge of schizophrenia.
AB  - Schizophrenia can develop in junior and senior high school students. Correct
      identification of schizophrenia symptoms is an important factor in subsequent
      healthcare. The present study conducted a multifaceted evaluation of factors
      associated with an absence of effect of an education program for improving
      knowledge of schizophrenia among parents of Japanese junior and senior high
      school students. Regarding discrimination of prodromal symptoms, the factors
      associated with an absence of effect of the education program were graduate
      school education, family income >110 000 USD, proximity to a person with
      schizophrenia, employment as a professional, and participation in welfare
      activities for people with mental illness. Regarding discrimination of
      schizophrenia, the factors associated with an absence of effect were a family
      income of 53 000 to 110 000 USD (P<0.05), and employment in production/labor
      service (P<0.05).

PMID- 22980341
TI  - Effect of single-session aerobic exercise with varying intensities on lipid
      peroxidation and muscle-damage markers in sedentary males.
AB  - OBJECTIVES: This study was conducted to evaluate the effect of the different
      intensity levels of single-session aerobic exercise on serum levels of lipid
      peroxidation and muscle damage markers in sedentary males. METHOD: Fifty one
      sedentary healthy males aged 21.76+/-1.89 years were randomly divided into four
      groups, with one control (n=10) and three treatment groups that attended single
      session aerobic exercise with low (n=14), moderate (n=14), and high (n=13)
      intensities. The serum levels of malondialdehyde (MDA) and creatine kinase (CK)
      were measured. RESULTS: Data analysis revealed a significant effect by the
      intensity levels of aerobic exercise on MDA (P=0.001) and CK (P=0.003) post-test
      when the participants in the treatment groups were compared with the control.
      When the intensity of aerobic exercise was increased, the amount of MDA and CK
      was also found to be increased. CONCLUSION: Single-session aerobic exercise can
      increase the amount of MDA and CK, suggesting that low intensity level of aerobic
      exercise should be utilized for more adaptation, and to prevent lipid
      peroxidation and muscle damage in sedentary males.

PMID- 22980342
TI  - Strengthening transversus abdominis in pregnancy related pelvic pain: the
      pressure biofeedback stabilization training.
AB  - Pregnancy related pelvic pain (PRPP) refers to musculoskeletal type of persistent
      posterior pelvic pain during and after pregnancy with feature of reduced
      endurance capacity for standing, walking and sitting which leads to severe
      discomfort and considerable impairment of daily activities. OBJECTIVE: To test
      the effect of pressure biofeedback stabilizer training, on the pain and
      dysfunction of a thirty year old subject who presented with PRPP. STUDY DESIGN:
      Single case design. OUTCOME VARIABLES: Oswestry pain and disability index, TrA
      efficacy. METHODOLOGY: An initial assessment was followed by treatment sessions
      which consist of 2 phases (Phase A & Phase B). The baseline phase (A) consists of
      conventional therapeutic exercises while the intervention phase (B) consists of
      pressure biofeedback training in conjunction with the conventional therapeutic
      exercises. RESULT: The study data demonstrated that the subject showed minimal
      improvement in pain, disability and TrA efficacy during the baseline phase and
      shown a steady improvement in all these variables during the intervention phase.
      CONCLUSION: Core muscle performance (TrA) can be retrained with pressure
      biofeedback stabilization training program in subject with PRPP thereby reducing
      pain and disability.

PMID- 22980344
TI  - Knowledge, attitude and practice of malaria transmission and its prevention among
      the school going adolescents in Wardha District, Central India.
AB  - BACKGROUND: Malaria causes 216 million cases and an estimated 655000 deaths in
      2010 in the world. 80.5% of the 109 billion population of India lives in malaria
      risk areas. The purpose of this study was to determine the knowledge, attitude
      and practices of malaria transmission and its prevention among the school going
      adolescents. METHODOLOGY: A cross sectional study was conducted among school
      going adolescents in the rural area of District Wardha, Maharashtra, Central
      India. 1096 adolescents from eight government secondary schools were randomly
      selected. A pre-designed, pre-tested questionnaire was used for data collection.
      Data thus generated was entered in Microsoft Excel and analyzed using Epi Info
      6.04 software package. Chi square value was used for testing the statistical
      significance. RESULTS: The mean age of the school going adolescents was 13.45 +/-
      1.91, for boys 13.43 +/- 1.99 and 13.48 +/- 1.85 year old for girls. About 84.7%
      of the respondents heard about the malaria disease and. 8.6% were aware about the
      causative agent. Transmission of malaria by mosquito bite was known to 69.8% of
      the adolescents. This was found significantly associated with male gender (X2 =
      4.21, p = 0.03). Some of the adolescents had misconception regarding the mode of
      transmission of malaria like houseflies (32.8%). Nearly half (51.1%) of the
      adolescents had knowledge of symptoms of malaria as fever. None of the
      adolescents were aware about the new strategy of insecticide treated bed nets.
      Majority of the adolescents (57.7%) knew commonest breeding habits of mosquitoes
      as dirty stagnant water. The main source of information about malaria to most of
      the adolescents was television and radio (51.7%). About 47.4% of the adolescents
      practiced the prevention of breeding places of the mosquitoes by cleaning the
      surrounding. Nearly one fifth (20.7%) of the adolescents were using mosquito net.
      During the study, 66 (6.02%) adolescents were suffering from fever out of that
      12.1% adolescents had taken self medication. CONCLUSION: Despite widespread
      knowledge about the morbidity of malaria, understanding about its transmission,
      treatment and prevention was low. It is imperative to involve the health workers
      to provide active support and empower teachers with information about malaria
      causation and prevention strategies so that such knowledge could be passed on to
      learners.

PMID- 22980343
TI  - Tobacco smoking: patterns, health consequences for adults, and the long-term
      health of the offspring.
AB  - Tobacco use started several centuries ago and increased markedly after the
      invention of the cigarette making machine. Once people start smoking they find it
      difficult to quit the habit. This is due to the addictive effect of nicotine in
      tobacco smoke. Various epidemiologic and laboratory studies clearly showed that
      smoking is associated with various diseases such as heart diseases, asthma and
      emphysema and the associated increase in morbidity and mortality of smokers.
      Several studies implicate nicotine as the causative factor in tobacco smoke.
      Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in
      an increase in the incidence of cancer in smokers. While the smoking habit is
      decreasing in developed countries, tobacco use increases in the developing
      countries. Smoking prevalence is also highest in poor communities and amongst
      those with low education levels. It is important to note that, although ther is a
      decline in the number of smokers in the developed countries, there is a three to
      four decades lag between the peak in smoking prevalence and the subsequent peak
      in smoking related mortality. It has been shown that maternal smoking induces
      respiratory diseases in the offspring. There is also evidence that parental
      smoking may program the offspring to develop certain diseases later in life.
      Various studies showed that maternal nicotine exposure during pregnancy and
      lactation via tobacco smoke of nicotine replacement therapy (NRT), program the
      offspring to develop compromised lung structure later in life with the consequent
      compromised lung function. This implies that NRT is not an option to assist
      pregnant or lactating smokers to quit the habit. Even paternal smoking may have
      an adverse effect on the health of the offspring since it has been shown that 2nd
      and 3rd hand smoking have adverse health consequences for those exposed to it.

PMID- 22980345
TI  - Healthy Architecture! Can environments evoke emotional responses?
AB  - We find environmental psychology at the intersection between architecture and
      psychology. This article discusses the ways in which individuals are affected by
      architecture, departing from an early source on the psychology of architecture
      and taking three architectural examples as illustrations: a public place in
      Berlin, a health environment in Sweden, and a fitness centre in Denmark. Each of
      these architectural examples creates what might be called its own psychological
      emotions, and these are analysed and discussed using a psychodynamic and
      existential attempt to understand the interrelationship between individuals and
      spatial reality. A health oriented existential approach is used as a
      methodological basis to conceptualise the psychological effects of various forms
      of architecture.

PMID- 22980346
TI  - Men's health in northern British Columbia: analysis and reporting of early
      intervention screening program data related to cardiovascular health.
AB  - Type 2 diabetes (T2D) is a well-established risk factor for cardiovascular
      disease (CVD). Higher rates of T2D are attributable to unhealthy lifestyle
      factors and a number of clinical and metabolic risk factors. There is paucity of
      research which investigated the association of lifestyle risk factors and
      metabolic markers amongst adult men in northern British Columbia (BC). Using a
      face-to-face screening questionnaire, we assessed the relationships between age,
      body mass index (BMI), and a number of CVD risk factors in a convenience sample
      of 123 eligible men recruited from communities across northern BC in February of
      2011. In regards to the metabolic risk factors measured through screening blood
      tests (lipid profiles; blood glucose) responses to the questionnaire were
      dichotomized into high and low risk categories. These dichotomized variables were
      subsequently used to determine if significant associations existed with each of
      the age category variable and a standard BMI categorical variable. There were
      significant linear relationships between the categorical BMI variable and a
      number of metabolic risk factors, as well as smoking history. Older age (40+
      years) was associated with higher BMI status (overweight/obese). Our findings
      provide compelling evidence that northern BC men possess a number of clinical,
      metabolic, and lifestyle risk factors associated with high CV risk. Future
      studies should examine other sociodemographic variables including occupation
      status, education attainment, and ethnicity, and other psychosocial determinants
      which include knowledge, attitudes, and perceptions (KAP) related to T2D and CV
      risk profile in adult men working and living in northern BC, Canada.

PMID- 22980347
TI  - Prevalence and correlates of erectile dysfunction among primary care clinic
      attendees in Nigeria.
AB  - INTRODUCTION: Erectile dysfunction (ED) has become a public health issue in
      Nigeria because of its increasing magnitude, association with chronic medical
      conditions and negative impact on sexual life. MATERIALS AND METHODS: Cross
      sectional study of 450 male patients aged 18-70 years who presented with non-ED
      related complaints. Main outcome measurements were prevalence and severity of ED
      which was assessed with International Index of Erectile Function (IIEF-5) and
      single-item sexual function questionnaire. Also assessed were socio-demographic
      characteristics, physical activities, sexual satisfaction and morbidities.
      RESULTS: The prevalence of ED was 55.1% (mild, moderate and severe were 32.6%,
      17.8% and 4.7% respectively). Prevalence of ED was significantly associated with
      age (p < 0.0001), marital status (p = 0.032), income (p = 0.001), social class (p
      = 0.004), physical activities (p = 0.006) and BMI (p = 0.012). Prevalence of ED
      was significantly high among men with diabetes mellitus (72.7%), hypertension
      (70.7%), peptic ulcer disease (70.4%) and previous prostate surgery (76.2%).
      Logistic regression showed dissatisfaction with sexual life (OR = 0.689, CI =
      1.233-5.866; p = 0.013) and having sexual activities less than desired (OR =
      3.331, CI = 1.416-7.839; p = 0.006) to be the most significant factors associated
      with ED. There was a strong positive correlation between the IIEF-5 and single
      item sexual function questionnaire (r = 0.747, p < 0.0001). CONCLUSION: The
      prevalence of ED is high among males attending a primary care clinic in Nigeria
      with non-ED related complaints. ED was more prevalent in men with chronic medical
      illnesses and sedentary lifestyle. Family physicians should inquire about this
      condition in these men and refer them early for specialist consultation.

PMID- 22980348
TI  - A comparative study of the lateral geniculate body of rat (Rattus norvegicus),
      bat (Eidolon helvum) and pangolin (Manis tricuspis).
AB  - In this study, the lateral geniculate bodies (LGB) of rats, bats and pangolins
      were compared using histological and quantitative histochemical parameters to
      observe possible modifications that enable these mammals to cope with their
      habitation particularly with respect to their diet. The study was conducted using
      ten adult Wistar rats, ten fruit bats and eight pangolins comprising of both
      sexes. After being sacrificed by cervical dislocation, their skulls were opened
      using bone forceps to expose the brains. The lateral geniculate bodies were
      excised from each brain tissue, homogenized and homogenate studied
      spectrophotometrically for the activities of lactate dehydrogenase (LDH), glucose
      6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), alkaline phosphatase
      (ALP) and acetylcholinesterase (AChE). The LGB tissue samples meant for
      histological studies were fixed in 10% formol calcium and processed for paraffin
      wax embedding. Serial sections of 3?m thickness were stained with Hematoxylin and
      Eosin (H & E) and Cresyl fast violet (CFV) stains. The stained tissues were
      studied under the light microscope. Application of one-way ANOVA statistical
      method showed that there were significant differences (p<0.05) in the activities
      of LDH, G-6-PDH, ACP, ALP and AChE of the LGB of the three mammals as revealed in
      the quantitative histochemistry of these enzymes and markers. Histological
      observations revealed no observable differences in the relative distribution of
      neurons and their supporting glial cells within the LGB of the three mammalian
      species. The comparison of the differences observed in the histological and the
      quantitative histochemical activities in these mammalian species revealed a
      variation in the visual perception and their individual peculiarities in relation
      to their mode and pattern of living.

PMID- 22980349
TI  - The impact of built environment on diabetic patients: the case of Eastern
      Province, KIngdom of Saudi Arabia.
AB  - At present, Diabetes mellitus is considered as one of the main threats to the
      human health in the 21st century. It may lead to severe conditions such as
      blindness, end-stage of renal disease, limb amputation and a variety of
      debilitating neuropathies. Previous researches indicated that diabetes is caused
      by a complex interaction of patient's genetics, life-style and environmental
      factors. They also highlighted that providing quality and healthy built
      environment to citizens including diabetic patients would prevent poor and
      unhealthy condition. The Kingdom of Saudi Arabia (KSA) is one of top ten
      countries in the prevalence of diabetes. Little researches though were conducted
      in KSA in regards to the effect of environmental conditions of the built
      environment. In 2011, the present researchers have carried out a pilot survey on
      a number of diabetic patients to find out the possible impact of built
      environment settings on the patient's lifestyle. The research explored whether
      diabetic patients use smart tools in their daily life to overcome the daily
      life's difficulties and perform their life as normal as possible. The results
      showed a close link between a poor home and environmental settings, the patient's
      lifestyle, and the patient's health status. It also highlighted the absence of
      smart tools and systems use. The paper argues that certain changes to the built
      environment must be done and to provide a healthy and safe environment for
      diabetic patients. This would help these patients to abandon their bad habits and
      adopt healthier lifestyle.

PMID- 22980350
TI  - Experiential relationship between malaria parasite density and some
      haematological parameters in malaria infected male subjects in Port Harcourt,
      Nigeria.
AB  - This study examined the experiential relationship between the parasite density
      and haematological parameters in male patients with Plasmodium falciparum
      infection in Port Harcourt, Nigeria reporting to malaria clinics. A total of one
      hundred and thirty-six (136) male patients were recruited. QBC haematological
      analysis, QBC malaria parasite specie identification and quantification and thin
      blood film for differential leucocytes count was used. The mean values of the
      haematological parameters in each quartile of parasite densities were determined
      using Microsoft Excel statistical package. Regression analysis was employed to
      model the experiential relationship between parasite density and haematological
      parameters. All regression relationships were tested and the relationship with
      the highest coefficient of determination (R2) was accepted as the valid
      relationship. The relationships tested included linear, polynomial, exponential,
      logarithmic and power relationships. The X- axis of the regression graphs stand
      for the parasite density while Y-axis stands for the respective haematological
      parameters  Neutrophil count had a negative  exponential relationship with the
      parasite density and is related to the parasite density by a polynomial equation
      model: ynm = -7E-07x2 - 0.0003x + 56.685.The coefficient of determination (R2)
      was 0.6140. This means that the rate of change of the parasitemia will depend on
      the initial value of the neutrophil. As the neutrophil increases, the parasitemia
      will tend to decrease in a double, triple and quadruple manner. The relationship
      between lymphocyte count, monocyte count and eosinophil count and parasite
      density was logarithmic and expressed by the following linear equation models:
      ylm = -2.371ln(x) + 37.296, ymm = 0.6965ln(x) + 5.7692 and yem = 0.9334ln(x) +
      4.1718 in the same order. Their respective high coefficients of determination
      (R2) were 0.8027, 0.8867 and 0.9553. This logarithmic relationship means that
      each doubling of monocyte count and eosinophil count will cause the same amount
      of increase in parasitemia whereas each doubling of lymphocyte count will cause
      the same amount of decrease in parasitemia. The best fitting regression model for
      total white cell count (WBC), haemoglobin concentration, packed cell volume
      (PCV)(haematocrit) and mean cell haemoglobin concentration (MCHC) and parasite
      density was a linear model and expressed by the following linear equation models:
      yWBCm = 1.2314x + 8533.8, yHbm = -0.0014x + 13.004, yPCVm = -0.0046x + 41.443 and
      yMCHCm = -0.0008x + 32.336. Their respective coefficients of determination are
      0.7397, 0.6248, 0.9758 and 0.8584.  This linear relationship means that as the
      parasite density is increasing that there is a corresponding decrease in
      haemoglobin concentration, PCV and MCHC and a corresponding increase in total
      white cell count.  The best fitting regression model between platelet count and
      parasite density is a power model with a very high coefficient of determination
      (R2=0.9938) and expressed by: yPltm = 278047x-0.122. These equation models could
      be very useful in areas where there may not be functional microscopes or
      competent microscopists and in medical emergencies.

PMID- 22980352
TI  - Health promotion education in India:  present landscape and future vistas.
AB  - 'Health promotion is the process of enabling people to increase control over and
      to improve their health'. This stream of public health is emerging as a critical
      domain within the realm of disease prevention. Over the last two decades, the
      curative model of health care has begun a subtle shift towards a participatory
      model of health promotion emphasizing upon practice of healthy lifestyles and
      creating healthy communities. Health promotion encompasses five key strategies
      with health communication and education as its cornerstones. Present study is an
      attempt to explore the current situation of health promotion education in India
      with an aim to provide a background for capacity building in health promotion. A
      systematic predefined method was adopted to collect and compile information on
      existing academic programs pertaining to health promotion and health
      education/communication. Results of the study reveal that currently health
      promotion education in India is fragmented and not uniform across institutes. It
      is yet to be recognized as a critical domain of public health education. Mostly
      teaching of health promotion is limited to health education and communication.
      There is a need for designing programmes for short-term and long-term capacity
      building, with focus on innovative methods and approaches. Public health
      institutes and associations could play a proactive role in designing and
      imparting academic programs on health promotion. Enhancing alliances with various
      institutes involved in health promotion activities and networking among public
      health and medical institutes as well as health services delivery systems would
      be more productive.

PMID- 22980351
TI  - Teachers' attitudes towards and comfort about teaching school-based sexuality
      education in urban and rural Tanzania.
AB  - Teachers' attitudes towards sexuality education are among the important
      predictors of their willingness to teach sexuality education programmes in
      schools. While there is a plethora of studies on teachers' attitudes towards
      sexuality in developed countries, there is a paucity of such studies in sub
      Saharan Africa in general and Tanzania in particular.  This study examined
      teachers' attitudes towards and comfort in teaching sexuality education in rural
      and urban Tanzania. The results show that an overwhelming majority of teachers in
      both rural and urban districts supported the teaching of sexuality education in
      schools, and the inclusion of a wide range of sexuality education topics in the
      curriculum. Nevertheless, though teachers expressed commitment to teaching
      sexuality education in schools, they expressed difficult and discomfort in
      teaching most of the key sexuality education topics. This implies that
      declaration of positive attitudes towards teaching sexuality education alone is
      not enough; there is a need for facilitating teachers with knowledge, skills and
      confidence to teach various sexuality education topics.

PMID- 22980353
TI  - The levels of zinc and molybdenum in hair and food grain in areas of high and low
      incidence of esophageal cancer: a comparative study.
AB  - The outcome of different studies on the role of Zn & Mo in esophageal cancer (EC)
      is conflicting. Here, the levels of those elements in hair as well as food grain
      of two different ethnic populations across two continents have been studied to
      explore their role in EC. Two different ethnic populations are taken from (i)
      Eastern Cape, South Africa (RSA), an area of very high incidence of EC and (ii)
      West Bengal, India, an area of low incidence of that disease. Each ethnic
      population is divided into two groups: case and control (n=30 for all groups).
      Hair samples from all groups and food grain from RSA and India are analyzed for
      Zn & Mo content. This study shows a strong correlation between reduced levels of
      those elements in hair and the development of EC in RSA (both Zn &Mo: p <
      0.0001), though it is only suggestive in Indian context (both Zn & Mo p ? 0.05).
      Interestingly, control group of RSA shows significantly reduced level of those
      elements in hair even with respect to Indian case group (Zn: p<0.001 & Mo: p<
      0.00001). Food grain from RSA has significantly reduced level of those elements
      with respect to India (both Zn & Mo: p <0.0001). This deficiency of Zn & Mo in
      food grains can be correlated to the deficiency of those elements in hair of RSA
      population. The deficiency of Zn & Mo can be correlated to the development of EC.

PMID- 22980354
TI  - Perception of the medical students on their future career in Qazvin University of
      Medical Sciences.
AB  - INTRODUCTION: Young physicians have many recruitment barriers in Iran. Therefore,
      for planning purpose, assessment of the attitudes of medical intern students
      towards their future career is important. METHODS: This cross-sectional study
      assessed the view points of 300 medical students through a self administered
      questionnaire. Data were analyzed using SPSS software with P value < 0.05.
      RESULTS: Two hundred and forty students (80%) of the students had responded to
      the questionnaire. Among them, 67.5% were female with mean age of 21.7+/-2.4. The
      main factors for deciding to study in medicine were their interest (64.1%),
      family pressure (13.5%) and social prestige of medical career (9.8%). The mean
      score of attitudes was 2.3+/-0.6. In total, 24.5% of students demonstrated not
      having interest in studying medicine. The most important cause of their interest
      change was long duration of education (24.4%) and cost of studying in medicine
      (13.8%). In total, 88.6% of students had negative viewpoint towards their medical
      career in future. CONCLUSION: In general, the attitude of medical students toward
      their future career was negative.

PMID- 22980355
TI  - Mixed panniculitis secondary to interferon beta-1a therapy in a woman with
      multiple sclerosis.

PMID- 22980358
TI  - Effects of hypothermia on brain injury assessed by magnetic resonance imaging
      after cardiopulmonary resuscitation in a porcine model of cardiac arrest.
AB  - OBJECTIVE: To evaluate the effects of hypothermia on cerebral edema and
      metabolism, a porcine model of cardiac arrest was assessed by magnetic resonance
      imaging during the first 72 hours after restoration of spontaneous circulation
      (ROSC). METHODS: Ventricular fibrillation was induced in 33 pigs. After 8 minutes
      of untreated ventricular fibrillation, 30:2 cardiopulmonary resuscitation was
      performed. After ROSC, 30 survival animals were randomly divided into
      normothermia group (n = 15) and hypothermia group (n = 15). The hypothermia group
      immediately received endovascular cooling to regulate temperature to 33 degrees
      C, which was maintained for 12 hours, followed by passive rewarming at 0.5
      degrees C/h to 37 degrees C. Diffusion-weighted imaging and (1)hydrogen proton
      magnetic resonance spectroscopy were acquired for each group at 6, 12, 24, and 72
      hours after ROSC. RESULTS: Compared with the normothermia group, the hypothermia
      group exhibited a higher 72-hour survival (73.3% vs. 33.3%, P = .028) and a
      superior neurological deficit score (P = .031). Cerebral injury was found in both
      groups, but a lesser decrease in the apparent diffusion coefficient and N-acetyl
      aspartate/creatinine (P < .05) and a greater increase in choline/creatinine (P <
      .05) were found in the hypothermia group. CONCLUSIONS: Magnetic resonance imaging
      could effectively detect the dynamic trend of cerebral injury in a porcine model
      of cardiac arrest within the first 72 hours after ROSC. Hypothermia produced a
      protective effect on neurological function by reducing brain edema and formation
      of adverse metabolites.

PMID- 22980357
TI  - Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D
      Aspartate receptors.
AB  - BACKGROUND: Mercury is a well-known neurotoxin implicated in a wide range of
      neurological or psychiatric disorders including autism spectrum disorders,
      Alzheimer's disease, Parkinson's disease, epilepsy, depression, mood disorders
      and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate
      mediated excitotoxicity, however, the underlying mechanisms remain poorly
      understood. Here, we examine the effects of various mercury concentrations
      (including pathological levels present in human plasma or cerebrospinal fluid) on
      cultured, rat cortical neurons. RESULTS: We found that inorganic mercuric
      chloride (HgCl2--at 0.025 to 25 MUM) not only caused neuronal degeneration but
      also perturbed neuronal excitability. Whole-cell patch-clamp recordings of
      pyramidal neurons revealed that HgCl2 not only enhanced the amplitude and
      frequency of synaptic, inward currents, but also increased spontaneous synaptic
      potentials followed by sustained membrane depolarization. HgCl2 also triggered
      sustained, 2-5 fold rises in intracellular calcium concentration ([Ca2+]i). The
      observed increases in neuronal activity and [Ca2+]i were substantially reduced by
      the application of MK 801, a non-competitive antagonist of N-Methyl-D-Aspartate
      (NMDA) receptors. Importantly, our study further shows that a pre incubation or
      co-application of MK 801 prevents HgCl2-induced reduction of cell viability and a
      disruption of beta-tubulin. CONCLUSIONS: Collectively, our data show that HgCl2
      induced toxic effects on central neurons are triggered by an over-activation of
      NMDA receptors, leading to cytoskeleton instability.

PMID- 22980359
TI  - Pulmonary hemorrhage and acute pulmonary thromboembolism after abciximab
      administration.

PMID- 22980360
TI  - Quick diagnosis units: avoiding referrals from primary care to the ED and
      hospitalizations.
AB  - PURPOSE: The aim of the present study was to determine whether quick diagnosis
      units (QDUs) can safely and efficiently avoid emergency department (ED) visits
      and hospitalizations. PATIENTS AND METHODS: We included a prospective cohort of
      4170 consecutive patients and a retrospective cohort of 3030 hospitalized
      patients. Medical records of hospitalized patients were reviewed to determine
      whether patients were stable enough for outpatient diagnostic workup. We studied
      primary care (PC) and ED referral patterns in two 25-month periods. Hospital and
      QDU costs were analyzed by microcosting techniques, and a survey was evaluated
      using care preferences. RESULTS: From December 2007 to December 2009, 66% QDU
      patients were referred from PC to ED and 25% from PC to QDU. From January 2010 to
      January 2012, 35% QDU patients were referred from PC to ED and 53% from PC to QDU
      (P < .0001). During the first period, 36% ED patients were referred to QDU and
      65% (retrospective cohort) were hospitalized, compared with 64% and 35%,
      respectively, during the second period (P < .0001). Between 84% and 91% of
      hospitalized patients were stable for QDU workup, and their hospitalization might
      have been avoided. Cost per process was ?3241.11 in hospitalized patients and
      ?726.47 in QDU patients. Most patients preferred the QDU model and were reluctant
      to first being transferred to ED. CONCLUSIONS: An increasing number of PC and ED
      patients were referred to the QDU. Hospitalizations might have been avoided in at
      least 84% of patients. Although QDU and hospitalization are similarly effective
      in reaching a diagnosis, the QDU model incurs fewer costs.

PMID- 22980361
TI  - Severe leptospirosis: treatment with intravenous corticosteroids and supportive
      care.
AB  - Leptospirosis is a common zoonotic infection worldwide and is recognized as an
      emerging public health problem. Although commonly thought of as a tropical
      disease, incidence in temperate climates is increasing, with recent outbreaks in
      the United States and Germany, among other countries. The disease presents with
      symptoms ranging from fever, headache, nausea, and vomiting to life-threatening
      multiorgan failure characterized by acute liver failure, nephritis, pulmonary
      hemorrhage, meningitis, and cardiac arrhythmia. We describe a case of an
      otherwise healthy 28-year-old man who had just returned from a 2-month trip to
      Southeast Asia. He presented to our emergency department twice after his return
      with the complaint of fever and malaise. Initially, he was treated with
      symptomatic measures and discharged home with malaria smears and blood cultures
      pending. On his final presentation before admission, he presented with severe
      fatigue, myalgia, acute renal failure, and marked thrombocytopenia. After several
      days, inpatient testing revealed the patient's leptospira antibody titer was
      markedly positive. Given the nonspecificity of patient symptoms, early diagnosis
      of leptospirosis can be challenging. Diagnostic uncertainty may lead to delay in
      recommended intravenous antibiotic treatment. We present a case of severe
      leptospirosis treated exclusively with supportive measures and intravenous
      corticosteroids.

PMID- 22980362
TI  - Hemoperitoneum semiquantitative analysis on admission of blunt trauma patients
      improves the prediction of massive transfusion.
AB  - BACKGROUND: The purpose of this study was to define whether the semiquantitative
      analysis of hemoperitoneum increases the accuracy of early prediction of massive
      transfusion (MT). METHODS: A retrospective review of severe trauma patients
      consecutively admitted to our trauma intensive care unit between January 2005 and
      December 2009 was conducted. Patients diagnosed with blunt abdominal trauma who
      had a computed tomography scan on admission were included. The hemoperitoneum
      size was defined using the Federle score on computed tomography as large,
      moderate, or minimal/none. The association between MT (>=10 U of packed red blood
      cells in the first 24 h) and moderate and large sizes of hemoperitoneum was
      assessed using a multiple logistic model. RESULTS: Of the 381 patients meeting
      the inclusion criteria, 270 (71%) were male; the mean age was 35.5 +/- 18.2 years
      and mean injury severity score was 23.4 +/- 17. Ninety-seven (26%) had large
      hemoperitoneum, 107 (28%) had moderate hemoperitoneum, and 177 (46%) had
      minimal/no hemoperitoneum. Eighty-three patients (22%) required MT. The positive
      predictive value for MT of a large hemoperitoneum was 41%, 23% for a moderate
      hemoperitoneum, and 10% for minimal/no hemoperitoneum (P < .001). The
      corresponding values for hypotensive patients were 61%, 32%, and 25%,
      respectively (P < .001). In the multivariate analysis model, only the large size
      of hemoperitoneum was significantly associated with MT (OR 6.4, 95% CI 2.9-14, P
      < .001, r(2) = 0.47). CONCLUSION: The assessment of the size of hemoperitoneum on
      admission substantially improves the prediction of MT in trauma patients and
      should be used to trigger and guide initial haemostatic resuscitation.

PMID- 22980363
TI  - Acute aortic dissection complicated by acute ischemic stroke: diagnostic
      challenges.

PMID- 22980364
TI  - Paroxysmal atrial fibrillation in a patient with severe carbon monoxide
      poisoning.

PMID- 22980365
TI  - Combination treatment with 17beta-estradiol and therapeutic hypothermia for
      transient global cerebral ischemia in rats.
AB  - OBJECTIVE: Therapeutic hypothermia is now regarded as the only effective
      treatment of global ischemic injury after cardiac arrest. Numerous studies of the
      neuroprotective effects of 17beta-estradiol have yielded conflicting results
      depending on administration route and dose. Herein, we investigated the
      neuroprotective effect of postischemic 17beta-estradiol administration combined
      with therapeutic hypothermia. METHODS: Twenty-one rats were randomly divided into
      4 groups: control (group I), therapeutic hypothermia (group II), 17beta-estradiol
      treatment (group III), and therapeutic hypothermia combined with 17beta-estradiol
      treatment (group IV). One rat was assigned to a sham operation group. With the
      exception of the sham-operated rat, all animals underwent transient global
      cerebral ischemia for 20 minutes by the 4-vessel occlusion method. Hypothermia
      was maintained at 33 degrees C for 2 hours in groups II and IV, and 17beta
      estradiol (10 MUg/kg) was intraperitoneally administered to rats in groups III
      and IV. Neurologic deficit scores and hippocampal cornu ammonis 1 neuronal injury
      were assessed 72 hours postischemia. RESULTS: The neurologic deficit score was
      not significantly different among the groups. The percentage of normal neurons in
      the hippocampal cornu ammonis 1 was 7.32% +/- 0.88% in group I, 53.65% +/- 2.52%
      in group II, 51.6% +/- 3.44% in group III, and 79.79% +/- 1.6% in group IV. The
      neuroprotective effect in the combined treatment group was markedly greater than
      in the single treatment groups, which suggests that hypothermia and 17beta
      estradiol work synergistically to exert neuroprotection. CONCLUSION: Postischemic
      administration of low-dose 17beta-estradiol appears to be neuroprotective after
      transient global ischemia, and its effect is potentiated by therapeutic
      hypothermia.

PMID- 22980366
TI  - Lack of efficacy of phenytoin in children presenting with febrile status
      epilepticus.

PMID- 22980367
TI  - Estimation of central venous pressure using inferior vena caval pressure from a
      femoral endovascular cooling catheter.
AB  - PURPOSE: Endovascular cooling using the femoral cooling catheter is widely
      practiced. Central venous pressure (CVP) monitoring in patients undergoing
      femoral endovascular cooling may require the placement of another catheter near
      the right atrium (RA). We sought to estimate the agreement between the CVP
      recorded from catheters placed in the superior vena caval pressure (SVCP) and the
      inferior vena caval pressure (IVCP) recorded from the femoral cooling catheter in
      patients undergoing femoral endovascular cooling. METHODS: We enrolled adult
      cardiac arrest survivors undergoing femoral endovascular cooling. A commercially
      available central venous catheter was placed in the SVC (superior vena cava) near
      the RA via subclavian venous access. Both SVCP and IVCP were recorded every 4
      hours during therapeutic hypothermia. Arterial pressure, heart rate, peak
      inspiratory pressure (PIP), and positive end expiratory pressure (PEEP) at the
      time of vena caval pressure measurements were obtained. RESULTS: A total of 323
      pairs of SVCP and IVCP measurements were collected. The correlation coefficient
      between SVCP and IVCP was 0.965 (P < .001). The mean difference between SVCP and
      IVCP was -0.45 mm Hg (SD, 1.27; 95% confidence interval, -0.59 to -0.31 mm Hg).
      The limits of agreement were -2.94 to 2.05 mm Hg. Vena caval pressures were
      significantly correlated with airway pressures (peak inspiratory pressure and
      positive end expiratory pressure), whereas the difference between SVCP and IVCP
      did not correlate with airway pressures. CONCLUSION: Inferior vena caval pressure
      measured via the femoral cooling catheter showed excellent agreement with CVP
      recorded from catheters placed in the SVC, which indicates that the femoral
      cooling catheter can be used for monitoring CVP.

PMID- 22980368
TI  - Ultrasonography of jugular vein as a marker of hypovolemia in healthy volunteers.
AB  - BACKGROUND: Our aim in this study was to use ultrasonography of internal jugular
      vein (IJV) instead of visual estimation by eye and to get more precise estimation
      of central venous pressure at supine position for estimating blood loss in
      healthy volunteers. METHODS: The values of the sonographic IJV collapse index and
      corrected IJV longitudinal length (cIJV LL) (vertical height of the jugular vein
      from the sternal angle of Louis plus 5 cm) were compared before and after blood
      donation. The correlations between the mean arterial pressure, pulse rate, IJV
      collapse index, and cIJV LL were analyzed using SPSS version 15.0 (SPSS, Chicago,
      IL) and G*Power version 3.1.2. (Franz Faul, Universitat Kiel, Germany) was used
      for power and sample size analysis. RESULTS: A total of 80 volunteers were
      enrolled in the study. The medians of cIJV LLs before and after blood donation
      were 6.67 (95% confidence interval [CI], 6.72-7.07) and 5.98 (95% CI, 6.09-6.40),
      respectively. The medians of IJV collapse indices before and after blood donation
      were 32.74 (95% CI, 32.73-39.50) and 38.88 (95% CI, 35.54-42.95), respectively.
      Preliminary results of our study revealed that cIJV LL and IJV collapse index
      were not well correlated (Spearman rho correlation coefficient, 0.257; r =
      0.128). CONCLUSION: Although, the IJV collapse index was not found to be a useful
      parameter for evaluation of hypovolemia, cIJV LL is more valuable marker for the
      detection of blood loss at bedside.

PMID- 22980369
TI  - Percutaneous noncoronary interventions during continuous mechanical chest
      compression with the LUCAS-2 device.

PMID- 22980370
TI  - Rupture of middle colic artery pseudoaneurysm.

PMID- 22980371
TI  - Successful resuscitation with thrombolysis of a presumed fulminant pulmonary
      embolism during cardiac arrest.

PMID- 22980372
TI  - Canadian rural-urban differences in end-of-life care setting transitions.
AB  - Few studies have focused on the care setting transitions that occur in the last
      year of life. People living in rural areas may have more difficult care setting
      transitions and also more moves in the last year of life as health changes occur.
      A mixed-methods study was conducted to gain an understanding of the number and
      implications or impact of care setting transitions in the last year of life for
      rural Canadians. Rural Albertans had significantly more healthcare setting
      transitions than urbanites in the last year of life (M=4.2 vs 3.3). Online family
      respondents reported 8 moves on average occurred in the last year of life. These
      moves were most often identified (65%) on a likert-type scale as "very
      difficult," with the free text information revealing these trips were often
      emotionally painful for themselves and physically painful for the decedent.
      Eleven informants were then interviewed until data saturation, with constant
      comparative data analysis conducted. Moving from place to place for needed care
      in the last year of life was identified as common and concerning for rural people
      and their families, with three data themes developing: (a) needed care in the
      last year of life is scattered across many places, (b) traveling is very
      difficult for terminally-ill persons and their caregivers, and (c) local rural
      services are minimal. These findings indicate planning is needed to avoid
      unnecessary end-of-life care setting transitions and to make needed moves for
      essential services in the last year of life less costly, stressful, and socially
      disruptive for rural people and their families.

PMID- 22980373
TI  - Reduction of mean arterial pressure and proteinuria by the effect of ACEIs
      (Lisinopril) in Kurdish hypertensive patients in Hawler City.
AB  - The angiotensin converting enzyme inhibitors (ACEIs) are a group of
      pharmaceuticals that are used primarily in treatment of hypertension and
      congestive heart failure, in some cases as the drugs of first choice. The renin
      angiotensin system is activated in response to hypotension, decreased sodium
      concentration in the distal tubule, decreased blood volume and in renal
      sympathetic nerve stimulation. This study examines the effects of angiotensin
      converting enzyme inhibitor (Lisinopril) on blood pressure (BP) 131 +/- 2.4 and
      proteinuria 0.198 +/- 0.005 in Kurd hypertensive patients, mean arterial blood
      pressure and proteinuria excretion were measured weekly along the period of 12
      weeks. Lisinopril significantly reduced mean arterial blood pressure, and
      attenuated proteinuria level in patients subjected to this study in lisinopril
      10mg dose dependent manner (p<0.05, n=24). In conclusion, lisinopril is of
      beneficial of renoprotection and in lowering BP.

PMID- 22980374
TI  - The intensity of intensive care: a patient's narrative.
AB  - This qualitative study involved action research to explore one woman's narrative
      of awareness, emotions and thoughts during treatment in an intensive care unit
      (ICU). The overarching aim is to increase insight into the thoughts, feelings and
      bio-psychosocial needs of the patient receiving treatment in ICU. Data was
      collected by means of narrative discourse analysis. Literature on the
      psychosocial and spiritual implications of ICU treatment is limited, and often
      patients have no recall of their treatment in an ICU at all. Documenting the
      illness narrative of this individual case is valuable as the participant could
      recall a certain amount of awareness, thoughts and emotions. These experiences
      included delirium, anxiety, helplessness, frustration and uncertainty. Once
      sedation was decreased, the patient's consciousness increased and she was
      confronted with thoughts and emotions that were unrealistic and frightening. It
      was found in this study that the opportunity to share a narrative on the emotions
      and awareness during treatment in an ICU had cathartic value and the participant
      suffered little symptoms of post traumatic stress syndrome, often associated with
      long term treatment in an ICU. Further research on this topic is necessary to
      improve ICU treatment, not only on a physical level, but with emphasis on the
      psychosocial and spiritual needs of the patient.

PMID- 22980375
TI  - Assessing tetraplegic patients' neuro-muscular adaptations to a six-week
      physiotherapeutic programme.
AB  - Spinal cord injury is a life-transforming condition of sudden onset that can have
      devastating consequences. A multidisciplinary, functional goal-oriented programme
      is required to enable the tetraplegic patient live as fully and independently
      life as possible. Physiotherapy is a very important part of the multidisciplinary
      team required to prevent many of the immobilization complications that may result
      in serious functional limitations, reduce overall morbidity and achieve well
      patterned recovery. This study therefore highlights the neuromuscular adaptations
      of tetraplegic patients to physiotherapy over a period of six weeks. Fifteen
      patients participated in this study and the results showed that even though
      changes in the musculoskeletal parameters are inevitable in tetraplegics, the
      extent/degree of reduction of these parameters was grossly minimized in the
      studied subjects through the administration of physiotherapeutic measures.
      However, further research using a large sample size will be required to evaluate
      the physiologic adaptations of the neuromuscular system to the physiotherapy
      interventions among patients with spinal cord injury.

PMID- 22980376
TI  - Obstetric fistula repair: experience with hospital-based outreach approach in
      Nigeria.
AB  - BACKGROUND: The huge back-log of obstetric fistula and the increasing incidence
      of the condition in Nigeria is a cause for concern for all stake-holders. This
      worrisome trend requires concerted effort with innovative strategies to redress
      the situation. METHODS: Hospital-based outreach programs sponsored by a non
      governmental organization with volunteer medical and health personnel were used
      to repair selected cases of obstetric fistula in Nigeria. RESULTS: Fifty-two
      relatively simple obstetric fistulas were selected out of 68 (selection rate
      76.5%) that presented for repair at 12 outreach programs in 5 different states of
      Nigeria. All the cases were repaired by one trained gynecological surgeon with a
      cure rate of 100%. The majority (50.0%) of the women were aged between 16 and 20
      years with a mean age of 23.8 years +/- 3.6. Most (80.9%) of the women in the
      study population were primiparous. The majority (50.0%) of the women were
      divorced at the time of their presentation for repair. A vast majority (76.9%) of
      the women had either primary level of education or no formal education. There was
      a preponderance (53.8%) of juxtacervical VVF among women in the study population.
      CONCLUSION: The use of hospital- based outreach approach to repair simple cases
      of obstetric fistula if multiplied could help reduce the large number of women
      living with unrepaired VVF in Nigeria.

PMID- 22980377
TI  - Management of myofascial pain of upper trapezius: a three group comparison study.
AB  - It is important to identify the most effective therapeutic modality in the
      management of myofascial trigger points (MTPt). Thus we aimed to study the effect
      of therapeutic ultrasound, laser and ischemic compression in reducing pain and
      improving cervical range of motion among patients with MTPt. Experimental study
      comparing three groups was designed as a 5 days trial, a co-relational design was
      considered. OUTCOME MEASURES: VAS for pain, provocative pain test using "soft
      tissue tenderness grading scheme" and active cervical lateral flexion using inch
      tape. Methods- Patients were divided into 3 groups, Gr 1 underwent treatment
      using therapeutic ultrasound, Gr 2 with therapeutic laser and Gr 3 with ischemic
      compression. Assessments were done on day 1 and day 5 of treatment respectively.
      RESULTS: ANOVA revealed improvement among all 3 groups as statistically
      significant difference (p<0.05) between the start and end of trial. Analysis
      using Chi square test shows a statistically significant difference in the
      improvement between laser and the other 2 groups. Mean difference in the change
      of scores between the assessments showed laser therapy to have a tendency towards
      progressive improvement over the treatment period and a better improvement than
      the other 2 groups. We conclude that laser can be used as an effective treatment
      regimen in the management of myofascial trigger points thereby reducing
      disability caused due to musculoskeletal pathology.

PMID- 22980379
TI  - Application of Moran's test with an empirical Bayesian rate to leading health
      care problems in Taiwan in a 7-year period (2002-2008).
AB  - PURPOSE: This study focused on using Moran's tests and logistic regression to
      detect changes in spatial clustering for females and males. METHODS: For spatial
      distribution analysis, an average morbidity rate for a 7-year period was
      calculated. Medical cases from Taiwan National Health Insurance (NHI) were used
      as the numerator, and the denominator was the average mid-year population.
      Spatial analysis techniques, with a morbidity-smoothing coefficient estimate
      based on the empirical Bayesian method, were incorporated and applied to global
      and local Moran tests. In addition, we used a logistic regression model to test
      the characteristics of similarity and dissimilarity between males and females and
      to formulate the common spatial risk. RESULTS: The mean found by local spatial
      autocorrelation analysis was used to identify spatial cluster patterns. There is
      great interest in discovering the relationship between leading health care
      problems and spatial risk factors. For example, in Taiwan, the geographic
      distribution of clusters where neoplasms were prevalent was found to closely
      correspond to the locations in the arseniasis-endemic areas of Southwestern and
      Northeastern Taiwan, as well as to locations in the Tainan urban area (for
      females) and clusters in Changhua County and Yunlin County (for males). The high
      density populations in urban areas showed carcinogen clusters in Taiwan's 3 main
      urban centers (i.e., Taipei, Taichung, and Kaohsiung) for female neoplasms.
      CONCLUSION: Cluster mapping helped clarify issues such as the spatial aspects of
      both the internal and external correlations for leading health care events. This
      information greatly assists in assessing spatial risk factors, which facilitates
      the planning of the most advantageous types of health care policies, as well as
      the implementation of effective health care services.

PMID- 22980378
TI  - The prevalence of metabolic syndrome and factors associated with quality of
      dialysis among hemodialysis patients in Southern Taiwan.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence of metabolic
      syndrome (MetS) among hemodialysis patients and factors associated with quality
      of dialysis. METHODS: Data were collected from 377 long-term hemodialysis
      patients who received hemodialysis treatment from clinics in Tainan and Kaohsiung
      between November 2009 and February 2010. MetS was defined using the criteria set
      in 2007 by the Bureau of Health Promotion, Department of Health, Taiwan. The
      measurement of Kt/V was used as an indicator of the quality of dialysis. A below
      1.4 Kt/V was considered poor dialysis quality. RESULTS: Results showed that the
      prevalence of MetS among the chronic hemodialysis patients in this sample was
      63.1%. Logistic regression results identified that the quality of dialysis in
      females was better than that in males (odds ratio (OR)=7.98, 95% confidence
      interval (CI): 2.52-25.31). Better quality dialysis was associated with older
      age, longer treatment time, and increased blood flow rate (OR=1.49, 13.63, and
      1.35, respectively). However, for every one kilogram increase in weight, the
      quality of dialysis decreased by 13 percents (OR=0.87, 95% CI: 0.83-0.92).
      CONCLUSIONS: MetS is common among hemodialysis patients. The prevalence of
      hypertension, hyperlipidemia, and hyperglycaemia were significantly higher among
      hemodialysis patients. Quality of dialysis related to gender, age, weight, and
      the dialysis prescription (treatment time and blood flow rate).

PMID- 22980380
TI  - Effects of selected socio-demographic characteristics of community health workers
      on performance of home visits during pregnancy: a cross-sectional study in Busia
      District, Kenya.
AB  - OBJECTIVE: Appropriate performance of home visits facilitates adoption of best
      practices at home and increased demand for facility based services. METHODS: It
      was a cross-sectional study in which community health workers were observed
      conducting home visits during pregnancy.  Data was collected using a structured
      questionnaire and the Consultant Quality Index (CQI-2 tool) on record keeping,
      use of job aids, counselling, client satisfaction and client enablement.
      Descriptive and inferential statistics were used. Relationships were determined
      using chi square and odds ratios. RESULTS: The study showed significant
      relationships of age with good record keeping (p = 0.0001), appropriate use of
      job aids (p=0.0001), client satisfaction (p = 0.018) and client enablement (p =
      0.001). Male CHWs were 1.6 times more likely to keep better records than females
      (OR 1.64 CI (1.02-2.63), while females were more likely to counsel and enable
      their clients OR 0.42 CI (0.25-0.71) and OR 0.29 CI (012-070) respectively when
      compared to men. Moreover, higher levels of education were associated with good
      record keeping OR 0.30 CI (0.19-0.49), p=0.0001; appropriate use of job aids OR
      0.30 CI (0.15-0.61) and to appropriately counsel their clients OR 0.34 CI (0.20
      0.58) than their lower literacy level counterparts. Experience of CHWs was
      associated with appropriate use of job aids (p = 0.049); client satisfaction (p =
      0.0001) and client enablement (p = 0.032). CONCLUSIONS: Socio-demographic
      characteristics of community health workers affect the performance of home visits
      in various ways. The study also confirmed that CHWs with lower literacy levels
      satisfy and enable their clients effectively.

PMID- 22980381
TI  - Contraceptive use among women with chronic medical conditions and factors
      associated with its non-use in Malaysia.
AB  - INTRODUCTION: Women with chronic medical conditions are at higher risk of adverse
      pregnancy outcomes, which may be minimized through optimal preconception care and
      appropriate contraceptive use. This study aimed to describe contraceptive use
      among women with chronic medical conditions and factors associated with its non
      use. METHODS: This study used cross-sectional data from a family planning survey
      among women with chronic medical conditions conducted in three health facilities
      in a southern state of Malaysia. A total of 450 married women in reproductive age
      (18-50 year) with intact uterus, and do not plan to conceive were analysed for
      contraceptive use. Both univariate and multivariate analysis was conducted to
      identify factors associated with contraceptive non-use among the study
      participants. RESULTS: A total of 312 (69.3%) of the study participants did not
      use contraceptive. Contraceptive non-use was highest among the diabetics (71.2%),
      connective tissue disease patients (68.6%) and hypertensive patients (65.3%).
      Only 26.3% of women with heart disease did not use contraceptive. In the
      multivariate analysis, contraceptive non-use was significantly more common among
      women who received their medical treatment in the health clinics as compared to
      those who received treatment in the hospital (adjusted odds ratio [OR]=1.75, 95%
      confidence interval [CI]: 1.09, 2.79), being in older age group of 41-50 year
      (adjusted OR=2.31, 95% CI: 1.19, 4.48), having children (adjusted OR=4.57, 95%
      CI: 1.66, 12.57) and having lower education (adjusted OR=2.87, 95% CI: 1.43,
      5.77). CONCLUSION: About two-third of women with chronic medical conditions who
      needed contraceptive did not use them despite the higher risk of pregnancy
      related complications. The high unmet need warrant an effective health promotion
      programme to encourage the uptake of contraceptives especially targeting women of
      older age group, low education and those who received their medical treatment at
      health clinics.

PMID- 22980382
TI  - Changing epidemiology of HIV in Mumbai: an application of the Asian epidemic
      model.
AB  - BACKGROUND: Mumbai is one of the most populous and high HIV prevalence cities in
      India. It has witnessed substantial changes in HIV-risk behaviors and a decline
      in HIV prevalence among high-risk groups during the past decade. AIM: To examine
      the changing pattern in the number of new HIV infections by transmission routes
      in Mumbai during 2000-2017. METHODS: We used the Asian Epidemic Model by dividing
      the adult population (aged 15 and above) into seven subgroups: brothel-based and
      non-brothel based female sex workers (FSWs), heterosexual clients of FSWs, men
      who have sex with men/transgendered people (MSM), injecting drug users (IDUs),
      general women and general men. The MSM subgroup included homosexual and bisexual
      men. RESULTS: New HIV infections among adults reduced by 86% during 2000-2010.
      The highest decline was among FSWs and their heterosexual clients (95%-98%),
      followed by MSM (82%), general women (77%), IDUs (51%) and general men (42%).
      Most new HIV infections during 2011-2017 are expected to occur among general
      women (1666) and general men (977) followed by MSM (715). Bisexual men were
      estimated to contribute about 14% of the new HIV infections among general women
      in 2010 and this proportion was estimated to increase to 19% in 2017. DISCUSSION:
      HIV prevention programs for MSM and the general population need to be
      strengthened. Ensuring early detection of HIV, and higher levels of consistent
      condom use by HIV-infected men and women are essential to prevent new HIV
      infections in future.

PMID- 22980383
TI  - The prevalence of hepatitis C Virus (HCV) among lichen planus patients and its
      clinical pattern at the University of Abuja Teaching Hospital, Gwagwalada, Abuja,
      Nigeria.
AB  - OBJECTIVE: The relationship between hepatitis C virus and Lichen Planus have been
      widely reported in the literature; although there are wide geographical
      variations in the reported prevalence of hepatitis C virus infection in patients
      with lichen planus. This study seeks to determine the prevalence of hepatitis C
      virus among lichen planus patients and its clinical morphological type in the
      University of Abuja Teaching Hospital, Gwagwalada Abuja, Nigeria.
      MATERIALS/METHODS: This study was conducted between January 2010 and December,
      2011 at the out patients Dermatological unit of the department of medicine at the
      University of Abuja Teaching Hospital Gwagwalada Abuja, Nigeria. Consecutive
      patients who had body eruptions suspected to be lichen planus were recruited and
      histology done for confirmation. The control group included patients' relations
      and some dermatology patients known to have low risk of hepatitis C virus
      infection and liver function tests done for both subjects and control after
      obtaining oral consent from them to participate in the study. RESULT: Anti- HCV
      antibodies were detected in nine cases (21.4%) and one case (3.3%) in the control
      group. This was statistically significant difference between the HCV antibody
      among the subject and control group (P<0.038). Hypertrophic lichen planus was the
      most frequent clinical type. Liver function test was not statistically
      significant among the subject and control group. CONCLUSION: Lichen planus and
      Hepatitis C virus appear to have a relationship and the prevalence rate was
      higher among the subject as compared to the control group in our environment.

PMID- 22980384
TI  - Reducing anxiety in stutterers through the association between "purpose in
      life/Ikigai" and emotions.
AB  - The human prefrontal lobe is more evolved than those of other mammals. As such,
      every person has an innate need to establish a meaningful life, often referred to
      as "Purpose in life (PIL)/ikigai", using the functioning of their prefrontal
      lobes. PIL/ikigai psychologically, and the prefrontal lobe physiologically, have
      common functions such as ambition, regulating emotion, and integrating
      psychological events. PIL/ikigai contributes to a decrease in anxiety influenced
      by a need for approval from others and stimulates pleasure and comfort, which may
      be related to the well-balanced secretion of neurotransmitters such as serotonin,
      dopamine, and ?-endorphin. Thus, a stutterer feels stress, i.e., anxiety, caused
      by perceived failure when engaging in conversations with others, which may be
      related to an imbalanced secretion of serotonin and dopamine. Therefore, previous
      work has suggested that PIL/ikigai may decrease anxiety in stutterers by
      decreasing the symptoms associated with stuttering.

PMID- 22980385
TI  - Action research on group consulting of family legal education for adolescent
      parents in China.
AB  - AIM: In this experimental study, we made an attempt to explore the approach and
      method to improve the legal cognition and family legal education level for
      adolescent parents. METHODS: 10 parents of students of grade two in a middle
      school of Chongqing in China were provided with group consulting and training. We
      adopted action research method to make overall assessment on the needs, execution
      and results of group consulting and training activity about family legal
      education for adolescent parents. RESULTS: After educating intervention group
      training of action research, the legal cognition level and the mastery and
      utilization of family legal educational method of adolescent parents get rising.
      CONCLUSION: Through the assessment of action research, the group training manner
      is a useful group consulting manner to make family legal education for adolescent
      parents. The program was feasible; the method was effective; the intervention
      effect was obvious.

PMID- 22980386
TI  - Knowledge, attitude and practice about rabies among children receiving formal and
      informal education in Samaru, Zaria, Nigeria.
AB  - Every year, about 50,000 people die of rabies of which about 55% of the
      mortalities occur in Asia and over 40% in Africa. Children are victims of up to
      50% of these mortalities. The figure is alarming and immediate action is required
      to stop this scourge. This study was carried out to assess the knowledge,
      attitude and practice about rabies among children attending primary schools
      located in the Ahmadu Bello University (ABU) premises and those outside the
      university as well as those receiving informal education. The participants for
      this study were children drawn by random selection from the schools chosen by
      purposive sampling. With the aid of questionnaires, information was obtained from
      a total of 477 children with 400 from formal educational settings among 3
      schools, and 77 from quaranic schools (almajiris) in the informal setting. More
      children receiving formal education were aware about the disease (50.8%) than
      those receiving informal education (32.5%), likewise those residing within ABU
      quarters (71%) were better informed than those residing outside ABU quarters
      (43.3%). Among children in the formal schools, 25.9% obtained information from
      friends and at school (25.9%), while in the informal setting, 56% obtained
      information from friends and only 16% from school. With regards to attitude and
      practice, 75.5% of children receiving formal education came from homes where dogs
      were vaccinated against rabies and 23.3% of them play with dogs they know, while
      11.1% of those receiving informal education vaccinate their dogs and fewer of
      them (14.3%) play with dogs known to them. Many children (65.7%) of those in
      formal schools know the role of dogs in rabies transmission, compared to only 8%
      in the informal schools. However, only 9.7% of children in formal schools
      associate both signs of furious and dumb form of rabies with the disease,
      compared with 28% in informal schools.  Among children bitten by dogs, 87.5% of
      those receiving informal education received hospital treatment compared to 63.7%
      of those going to formal schools. About 13% in each of the two categories
      received traditional treatment. It is, therefore, important for children to be
      properly educated about rabies so that they can avoid dogs, recognise potential
      exposures, report to a responsible adult and pass on the knowledge to their
      peers.

PMID- 22980387
TI  - Incidence of birth asphyxia as seen in central hospital and GN children's clinic
      both in Warri Niger Delta of Nigeria: an eight year retrospective review.
AB  - BACKGROUND: Birth asphyxia is one of the commonest causes of neonatal morbidity
      and mortality in developing countries. Together with prematurity and neonatal
      sepsis, they account for over 80% of neonatal deaths. AIM: To determine the
      incidence and mortality rate of birth asphyxia in Warri Niger Delta of Nigeria.
      MATERIALS AND METHOD: Recovery of case notes of all the newborn babies seen from
      January 2000 to December 2007 at Central Hospital Warri and GN children's Clinic,
      Warri, was undertaken. They were analyzed and those with birth asphyxia were
      further analyzed, noting the causes, severity of asphyxia, sex of the babies,
      management given. RESULTS: A total of 864 out of 26,000 neonates seen within this
      period had birth asphyxia. 525 (28/1000 live births) had mild asphyxia while 32%
      were severely asphyxiated. 61.5% of the asphyxiated were born at maternities,
      churches or delivered by traditional birth attendants or at home. Prolonged
      labour was the commonest cause of asphyxia and asphyxia was more in neonates from
      unbooked patients. CONCLUSION: The incidence of bith asphyxia in Warri is
      28/1000. Majority of patients are from prolonged labour and delivery at
      unrecognized centres. Health education will dratically reduce the burden of
      asphyxia neanatorum as unsubtanciated religous beliefs have done a great havoc.

PMID- 22980388
TI  - The isoflavone-rich fraction of the crude extract of the Puerariae flower
      increases oxygen consumption and BAT UCP1 expression in high-fat diet-fed mice.
AB  - Puerariae flower extract (PFE) is a crude extract of the Kudzu flower. Previous
      studies have shown that PFE supplementation exerts anti-obesity and anti-fatty
      liver effects in high-fat diet-fed mice. In this study, we aimed to identify the
      PFE components responsible for these effects and to determine their influence on
      energy expenditure and uncoupling protein 1 (UCP1) expression. Experiments were
      conducted on C57BL/6J male mice classified into 3 groups: (1) high-fat diet-fed
      (HFD), (2) high-fat diet-fed given PFE (HFD + PFE), and (3) high-fat diet-fed
      given the PFE isoflavone-rich fraction (HFD + ISOF). All groups were fed for 42
      days. The HFD + PFE and HFD + ISOF groups showed significant resistance to
      increases in body weight, hepatic triglyceride level, and visceral fat compared
      to the HFD group. These groups also exhibited significant increases in oxygen
      consumption and UCP1-positive brown adipose tissue (BAT) area. Our results
      demonstrate that the active ingredients in PFE are present in the ISOF and that
      these compounds may increase energy expenditure by upregulation of BAT UCP1
      expression. These findings provide valuable information regarding the anti
      obesity effects of isoflavones.

PMID- 22980389
TI  - The delivery and quality of sexually transmitted infections treatment by private
      general practitioners in Windhoek Namibia.
AB  - INTRODUCTION: The main objective for this study was to investigate the quality of
      Sexually Transmitted Infections (STI) treatment and control by the private sector
      in Namibia. METHOD: This was a cross-sectional study employing quantitative
      methodology using different methods of data collection. A self-administered
      questionnaire exploring General Practitioners (GPs) perceptions of factors that
      influence the way they manage Sexually Transmitted Infections (STI) which was
      then concluded with the face to face interviews and the checklist that was used
      while doing observations in the consulting rooms. RESULTS: A total of 50 private
      general practitioners in the area of Windhoek were interviewed, 48 self
      administered questionnaires plus all checklists were received back from the
      private general practitioners. None of the private general practitioners
      interviewed had specific training in the syndromic management of the STIs. The
      86% of all patients were seen by these private general practitioners on a medical
      aid, while 14 % pay cash for service provided. With regard to Urethral Discharge,
      an average of 56.5% of GPs could treat urethral discharge correctly as per the
      Namibian syndromic approach guidelines. None of the GPs could demonstrate the
      correct treatment of genital ulcer (whether they received medical aid or not) as
      recommended in the syndromic approach guidelines in Namibia (GRN, 1999; 2000).
      Only 28% of the GPs could demonstrate the correct treatment of Pelvic
      Inflammatory Disease (PID) as per the syndromic management of the STIs. For
      patients without medical aid the drugs prescribed and their dosages for PID are
      correct but the frequencies are not in line with the guidelines as for patients
      with medical aid. DISCUSSION: In general, patients presenting with STIs to the
      GPs in private practices are not given quality of care because not all private
      general practitioners have time to do investigations, counseling, give condoms
      and to notify the partners of those with urethral discharge, genital ulcers and
      PID looking for treatment.

PMID- 22980391
TI  - The cause of divorce among men and women referred to marriage and legal office in
      Qazvin, Iran.
AB  - BACKGROUND: Marital separation and divorce can be the most unpleasant event in
      the adult's life, and families will be hurt by divorce event. The prevalence of
      divorce has been increased in last decades. Therefore, this study was conducted
      to identify the divorce cause among the divorce seeking men and women in Qazvin,
      Iran. METHOD: This cross-sectional study was conducted among 572 (400 women and
      172 men) subjects who requested for divorce and were referred to divorce and
      marriage office of Qazvin province during 3 month in 2009. Data were collected by
      self - administered questionnaire, interviewing subjects and using Likert scale.
      Data were analyzed by Chi- Square test and Mann-Whitney (SPSS version 16).
      RESULTS: The participants of the study included 400 women (26.5 +/- 7.4 years)
      and 172 men. In view points of women the primary wrong mate selection was main
      cause of divorce (59.8%), but the men believed that the families and relatives
      interference was the main reason for separation (43.7%). Among the respondents,
      mean score of "dependency to their families" and "unmet emotional needs" were
      3.44 +/- 1.6 and 3.86 +/- 1.4 respectively. In addition mean score of infertility
      among men and women were 1.37 +/- 1.0 and 1.29 +/- 0.9 respectively. CONCLUSION:
      Wrong mate selection, unmet emotional needs, families' interference, and
      "dependency to families" are more important factors than traditional factors
      which are sexual or physical factors.

PMID- 22980390
TI  - Predicting acute viral hepatitis serum markers (A and E) in patients with
      suspected acute viral hepatitis attending primary health care centers in Baghdad:
      a one year cross-sectional study.
AB  - BACKGROUND: Viral hepatitis is an important preventable infectious disease with
      various rates of occurrence in different areas of the world. The main objective
      of the present study was to evaluate the role of some risk factors in predicting
      a positive acute viral hepatitis marker among patients with suspected acute viral
      hepatitis in a primary health care setting in Baghdad. Besides, finding out the
      occurrence of jaundice, contribution of viruses A and E to the cases that have
      occurred in Baghdad province was also searched for. METHODS: Over a period of 1
      year a descriptive cross sectional study was carried out at the primary health
      care centers in Baghdad. A questionnaire form was used to collect data about
      demographic factors and the results of the investigations. Total serum bilirubin
      and bilirubin in urine were done at the primary health care center laboratory.
      The rest of the sera samples were sent to Hepatitis referral Lab at Central
      Public Health Laboratory (CPHL) to be tested for anti HAV IgM and anti HEV IgM
      using ELISA technique. RESULTS: A total of 7,576,372 consultations to primary
      health care centers were recorded in Baghdad. Among those a total of 2,692 cases
      (35.5 per 100,000 consultations) were labeled as acute viral hepatitis cases. A
      positive hepatitis viral marker (A, B, C and E) was found in 1,332 cases (17.6
      per 100,000 consultations). More than two fifths (44.8%) of cases were positive
      for anti-HAV antibodies and another 1.6% had positive anti-HEV antibodies.
      CONCLUSION: During 1 year period, the rate of occurrence of suspected acute viral
      hepatitis cases was 35.5 per 100000 of consultations to the primary health care
      centers in Baghdad. Of the total suspected cases, only 17.6 per 100000 of the
      consultations were positive for one of the viral hepatitis markers. Those who
      tested positive for one of the viral hepatitis markers represent 49.5% of the
      suspected cases. Proportion of anti HAV IgM positive tests among suspected cases
      was 44.8%. Factors that were able to predict positive Anti HAV IgM were (younger
      age group, negative history of cupping or tattooing, negative past history of
      jaundice). Male gender was the least important predictor of a positive case for
      anti HAV IgM. Proportion of Anti HEV IgM positive tests among suspected cases was
      1.6%. Of the factors studied, only age was able to predict a positive Anti HEV
      IgM in those more than 15 years. Further studies are recommended.

PMID- 22980392
TI  - The interface of nutritional practices of selected basketball players of Nnamdi
      Azikiwe University, Awka, on performance.
AB  - The nutritional practices of athletes are critical to sports performance, since
      good result is the goal or expectations of all sports stake-holders, coaches,
      sports administrators/managers and spectators alike, therefore the issue of good
      nutrition regarding these "human machines" (athletes), calls for serious
      attention. This research, therefore tried to examine the nutritional practices of
      some selected Basketball players of Nnamdi Azikiwe University (UNIZIK) Awka, in
      Anambra State of Nigeria. Some 59 male and female Basketball (B/B) players were
      purposefully selected to participate in the study. A self developed questionnaire
      (r = 0.71) was administered on them and Weighted Mean Score (WMS). This was in an
      attempt to ascertain whether the dietary manipulations as practiced by these
      athletes immediately before competition, affect their performance, in any way.
      Findings revealed daily inadequate consumption of required proportion of
      nutrients and very poor timing of meals by the players.

PMID- 22980393
TI  - An increase in the content of cell wall-bound phenolics correlates with the
      productivity of triticale under soil drought.
AB  - The objective of this study was to investigate whether the content of cell wall
      bound phenolics can simultaneously influence both the productivity and the water
      status of triticale under soil drought conditions. Two parallel treatments were
      carried out. The T1 treatment involved plants being subjected to soil drought
      twice, during the tillering phase and then during the flowering phase. The T2
      treatment included drought only during the flowering phase. After T1 treatment,
      the majority of cultivars exhibited better PSII functioning at the flowering
      phase in comparison to T2, which could be related to better adaptation of the
      photosynthetic apparatus to leaf dehydration. Simultaneously, the higher activity
      of the photosynthetic apparatus of flag leaves for T1 was significantly
      correlated with the higher content of cell wall-bound phenolics. The dry mass of
      plants was markedly lower in the T1 treatment and was correlated with a higher
      content of cell wall-bound phenolics. Moreover, cultivars subjected to the T1
      treatment showed a significantly higher water content in comparison to the T2
      treatment. The delay in the leaf rolling and the ageing of plants in the T1
      treatment, which induced a higher level of cell wall-bound phenolics, was visual
      proof of the improvement in the water status of plants. Phenolic compounds that
      form cross-bridges with carbohydrates of the cell wall can be considered a more
      effective biochemical protective mechanism than free phenolics during the
      dehydration of leaves. This potentially higher level of effectiveness is likely
      the result of the double action of phenolic compounds, both as photoprotectors of
      the photosynthetic apparatus and hydrophobic stabilizers, preventing water loss
      from the apoplast.

PMID- 22980394
TI  - [Anaesthetic care in ophthalmology].

PMID- 22980395
TI  - [Postoperatory analgesia for minimally invasive cardiac surgery: which is the
      ideal technique?].

PMID- 22980396
TI  - [Retrospective descriptive study about the use of levosimendan in children
      undergoing surgical correction for congenital heart disease].
AB  - OBJECTIVES: To describe the use of levosimendan for compassionate use in children
      undergoing surgery for congenital heart disease, as well as survival rates, and
      the variations in the haemodynamic and analytical variables studied. MATERIAL AND
      METHODS: An observational retrospective descriptive study was performed, using a
      review of clinical histories, from May 2005 to January 2010. Haemodynamic and
      analytical variables pre- and post- levosimendan administration, drugs used, and
      their dosages, and any adverse reactions were recorded. RESULTS: Forty two
      children, 38 of them undergoing surgical correction, between the ages of four
      days and 5.75 years (median 92 days) were included. The drug was infused on 46
      occasions. Four children received two doses. The infusion rate was among 0.1 to
      0.6 MUg * kg-1 * min-1. Only one patient received a loading dose. In 15
      administrations (32.6%), the same dose was maintained throughout the infusion
      period. In 19 cases (41.3%), the dose was increased or decreased according to the
      need for vasoactive support. In surgical patients, overall survival after 30 days
      of the administration, calculated using the Kaplan-Meier method, was 80%. Blood
      lactate levels were statistically associated with mortality (P<.001).
      CONCLUSIONS: There were no uniform criteria for using levosimendan, and it was
      only used as a rescue drug. Overall survival was similar to that reported in
      adult clinical trials. Clinical trials also need to be carried out in paediatric
      patients to determine the role of levosimendan in surgical practice, in order to
      develop and establish a clinical protocol for its use in children.

PMID- 22980397
TI  - [Transitory acute atrioventricular block in an African patient: consider sickle
      cell anemia].
AB  - This case report shows a rare cardiac complication of sickle cell anemia in a
      young African patient which was an acute paroxysmal atrio-ventricular block.
      Acute paroxysmal atrioventricular block is a rare complication of polymerization
      of hemoglobin S during sickle cell disease. Hence, sickle cell anemia should be
      considered as a cause of auriculoventricular block in black African patients.
      Cardiac complications of sickle cell anemia are presented in this article.

PMID- 22980398
TI  - Evaluation of the current treatment concepts in Germany, Austria and Switzerland
      for acute traumatic lesions to the prepatellar and olecranon bursa.
AB  - BACKGROUND: Although traumatic lacerations of the olecranon (OB) and praepatellar
      bursae (PB) are common entities often associated with complications, no study
      could be found on this injury. The aim of this study was to survey the current
      treatment concepts for acute traumatic laceration of the OB and PB in Germany,
      Austria and Switzerland. MATERIALS AND METHODS: An international online survey
      was conducted among orthopaedic and trauma surgeons in Germany (TraumaNetwork
      DGU), Austria (Austrian Society of Trauma (OGU) and Orthopaedic (OGO) Surgeons)
      and Switzerland (Swiss Orthopaedic Surgeons and Swiss Society of Infectious
      Disease (CH)) (n=1967). The survey comprised of five demographical questions, the
      current treatment concepts were evaluated using a case study. RESULTS: The
      overall-response-rate was 16% (12-46%). 88% of the responding physicians were
      male, aged 47.5 +/- 10.2 years with a mean working experience of 20.1 +/- 10.6
      years. 54% of the surveyed physicians were either senior or chief physicians.
      Treatment concepts varied significantly between DGU and OGO/CH (p=0.02/p=0.006),
      no significant differences could be found between DGU and OGU. Generally, German
      and Austrian trauma surgeons favoured bursectomy (86.7%/90.9%) and immobilisation
      (68.3%/77.3%). Austrian orthopaedic surgeons performed fewer bursectomies (69.3%)
      but had the highest proportion for administering antibiotics (73.9%). Less than
      50% of Swiss physicians indicated bursectomy as a treatment option. CONCLUSION:
      Overall, this survey revealed a significant heterogeneity in treatment approaches
      in Central Europe. Further evidence is needed to identify the best treatment
      concepts for traumatic lacerations of the OB and PB.